PMID- 15457542
TI  - Oocyte-selective expression of MT transposon-like element, clone MTi7 and its
      role in oocyte maturation and embryo development.
AB  - Previously, we found MT transposon-like element, clone MTi7 (MTi7) is highly
      expressed in the mouse ovary. Here, we show that the MTi7 is expressed in the
      oocyte from the primordial to the preovulatory follicles. For RNA interference
      (RNAi), double stranded RNAs (dsRNAs) were prepared for MTi7 and c-mos, a control
      gene with known functions. Each dsRNA was microinjected into germinal vesicle
      (GV) stage oocytes or zygotes with pronuclei (PN), after which developmental
      changes, mRNA expression, and nuclear and microtubular organization were
      analyzed. We found a 43.4-53% GV arrest in the microinjected oocytes with a
      concomitant decrease in targeted mRNA expression. In MTi7 dsRNA-injected early
      and late PN zygotes, a 92.9% 1-cell arrest and 76.9% 2-cell arrest were observed,
      respectively. This is the first report of an oocyte-selective expression of MTi7
      mRNA, and our results strongly suggest that MTi7 involved in the nuclear membrane
      breakdown during oocyte maturation and embryo development.

PMID- 15457543
TI  - Implication of cAMP during porcine sperm capacitation and protein tyrosine
      phosphorylation.
AB  - Second messengers are involved in sperm fertilizing potential, as both motility
      and the acrosome reaction are influenced by cAMP. Moreover, the activity of
      cyclic nucleotides is implicated in the appearance of tyrosine phosphorylated
      sperm proteins, which is associated with capacitation in the mammalian
      spermatozoa. Nevertheless, the involvement of the cAMP/protein kinase A (PK-A)
      pathway during pig sperm capacitation may be different from that observed in
      other mammals. The objective of the present study was to clarify the cAMP/PK-A
      pathway during the capacitation of porcine spermatozoa and to evaluate this
      impact on the p32 sperm tyrosine phosphoprotein appearance. The presence of p32
      was assessed after incubating fresh pig sperm with IBMX/db-cAMP, H-89, a PK-A
      inhibitor or bistyrphostin, a tyrosine kinase inhibitor, in capacitating (CM) or
      non-capacitating conditions (NCM) by immunoblotting SDS-extracted and separated
      sperm proteins using an anti-phosphotyrosine antibody. When pig spermatozoa were
      incubated in CM supplemented with H-89 (50 microM) or bistyrphostin (1.2 microM),
      capacitation decreased significantly (P < 0.001). The p32 sperm tyrosine
      phosphoprotein, previously shown to be associated with capacitation of porcine
      sperm though not necessarily an end point of this phenomenon, was not modulated
      by IBMX/db-cAMP (100 microM/1 mM), H-89 (50 microM) nor bistyrphostin (1.2
      microM). Our results indicate, therefore, that pig sperm are regulated somewhat
      differently than as described for other mammals, because although the cAMP/PK-A
      and tyrosine kinase pathways are involved in capacitation, they do not influence
      the appearance of p32.

PMID- 15457544
TI  - Cytoplasmic localization during testicular biogenesis of the murine mRNA for
      Spam1 (PH-20), a protein involved in acrosomal exocytosis.
AB  - The Sperm Adhesion Molecule1 (SPAM1) is the most widely conserved sperm antigen
      with important roles in mammalian fertilization. Light and electron microscopy
      were used to localize, by in situ hybridization, the cellular and subcellular
      sites of Spam1 mRNA in the murine testis. Transcripts were first detected in step
      3 round spermatids, gradually increased until step 8 and abruptly decreased
      between steps 9-11. They were predominantly localized near the ER and were not
      dispersed throughout the cytoplasm. Immunohistochemistry revealed that Spam1 is
      present on both the head and tail of sperm in the seminiferous tubules, and
      provided support for transcriptional regulation of its transcript.
      Immunocytochemistry confirmed the location of Spam1 on the tail of testicular
      sperm and demonstrated that it is localized to both the principal piece and the
      midpiece. Spam1 on epididymal sperm is localized to the midpiece of the tail and
      changes from a uniform distribution on the head in the caput to a regionalized
      pattern, first on the posterior and then on the anterior head, in caudal sperm.
      Spam1 on the surface of caudal sperm was shown to mediate the increase in
      acrosome reactions induced by the synergistic effects of HA and progesterone, as
      confirmed in sperm from the Rb(6.16) translocation-bearing mice which are Spam1
      mutants. The similar response of human and mouse sperm to these agonists of the
      acrosome reaction, underscores the usefulness of the mouse as a model to study
      physiological aspects of SPAM1 in humans where, unlike the mouse, it is the only
      sperm hyaluronidase.

PMID- 15457545
TI  - A cyclic adenosine 3',5'-monophosphate-induced tyrosine phosphorylation of Syk
      protein tyrosine kinase in the flagella of boar spermatozoa.
AB  - A cyclic adenosine 3',5'-monophosphate (cAMP)-dependent protein tyrosine
      phosphorylation is involved in the expression of fertilizing ability in mammalian
      spermatozoa. However, there are only limited data concerning the identification
      of protein tyrosine kinase (PTK) that is activated by the cAMP signaling. In this
      study, we have shown data supporting that boar sperm flagellum possesses a unique
      cAMP-protein kinase A (PKA) signaling cascade leading to phosphorylation of Syk
      PTK at the tyrosine residues of the activation loop. Ejaculated spermatozoa were
      washed and then incubated in a modified Krebs-Ringer HEPES medium (mKRH)
      containing polyvinyl alcohol (PVA) plus 0.1 mM cBiMPS (a cell-permeable cAMP
      analog), 0.25 mM sodium orthovanadate (Na3VO4) (a protein tyrosine phosphatase
      (PTP) inhibitor) or both at 38.5 degrees C for 180 min. Aliquots of the sperm
      suspensions were recovered before and after incubation and then used to detect
      sperm tyrosine-phosphorylated proteins by Western blotting and indirect
      immunofluorescence. In the Western blotting, the anti-phosphotyrosine monoclonal
      antibody (4G10) recognized several bands including 72-kDa protein in the protein
      extracts from spermatozoa that were incubated solely with cBiMPS. The tyrosine
      phosphorylation in these sperm proteins was dependent on cBiMPS and enhanced by
      the addition of Na3VO4. The 72-kDa tyrosine-phosphorylated protein was apparently
      reacted with the anti-phospho-Syk antibody (Tyr525/526). Indirect
      immunofluorescence revealed that the connecting and principal pieces of
      spermatozoa incubated with cBiMPS and Na3VO4 were stained with the anti-phospho
      Syk antibody. However, the reactivity of the 72-kDa protein with the anti-phospho
      Syk antibody was reduced by the addition of H-89 (a PKA inhibitor, 0.01-0.1 mM)
      to the sperm suspensions but not affected by the pretreatment of spermatozoa with
      BAPTA-AM (an intracellular Ca2+ chelator, 0.1 mM). Fractionation of
      phosphorylated proteins from the spermatozoa with a detergent Nonidet P-40
      suggested that the 72-kDa tyrosine-phosphorylated protein might be a cytoskeletal
      component. Based on these findings, we have concluded that the cAMP-PKA signaling
      is linked to the Ca2+-independent tyrosine phosphorylation of Syk in the
      connecting and principal pieces of boar spermatozoa.

PMID- 15457546
TI  - Immunolocalization of cubilin, megalin, apolipoprotein J, and apolipoprotein A-I
      in the uterus and oviduct.
AB  - Spermatozoa maturation and capacitation occurring in the male and female
      reproductive tracts, respectively, involves the remodeling of the spermatozoa
      plasma membrane. Apolipoprotein J (apoJ) and apolipoprotein A-I (apoA-I) have
      been implicated in the process of lipid exchange from the spermatozoa plasma
      membrane to epithelial cells lining the male reproductive tract. Evidence
      suggests that this process is mediated by the cooperative action of the endocytic
      lipoprotein receptors megalin and cubilin, which are expressed at the apical
      surface of absorptive epithelia in various tissues, including the efferent ducts
      and epididymis. Here, we investigated the possibility that these receptors and
      their lipid-binding ligands, apoJ and apoA-I, might function similarly in the
      female reproductive tract. We show that megalin and cubilin are expressed in the
      uterine epithelium at all stages of the estrous cycle, maximally during estrous
      and metestrous stages. In the oviduct, there is pronounced expression of both
      megalin and cubilin in the nonciliated cells of the proximal oviduct and
      epithelial cells of the distal oviduct, particularly during estrous and
      metestrous stages. In both uterine and oviduct epithelial cells, megalin and
      cubilin were located on the apical regions of the cells, consistent with a
      distribution at the cell surface and in endosomes. ApoJ and apoA-I were both
      detected in apical regions of uterine and oviduct epithelial cells. Secretory
      cells of the uterine glands were found to express apoJ and apoA-I suggesting that
      the glands are a site of synthesis for both proteins. In summary, our findings
      indicate that megalin and cubilin function within the female reproductive tract,
      possibly mediating uterine and oviduct epithelial cell endocytosis of apoJ/apoA-I
      lipid complexes and thus playing a role in lipid efflux from the sperm plasma
      membrane, a major initiator of capacitation.

PMID- 15457547
TI  - Several signaling pathways are involved in the control of cattle oocyte
      maturation.
AB  - The main limit of in vitro production of domestic mammal embryos comes from the
      low capacity of in vitro matured oocytes to develop after fertilization. As soon
      as they are separated from follicular environment, oocytes spontaneously resume
      meiosis without completion of their terminal differentiation. Roscovitine (ROS),
      an inhibitor of M-phase promoting factor (MPF) kinase activity reversibly blocks
      the meiotic resumption in vitro. However, in cattle maturing oocytes several
      cellular events such as protein synthesis and phosphorylation, chromatin
      condensation and nuclear envelope folding escape ROS inhibition suggesting the
      alternative pathways in oocyte maturation. We compared the level of synthesis and
      phosphorylation of several protein kinases during bovine cumulus oocyte complex
      (COC) maturation in vitro in the presence or not of epidermal growth factor (EGF)
      and ROS. We showed that during the EGF-stimulated maturation, ROS neither
      affected the decrease of EGF receptor (EGFR) nor did inhibit totally its
      phosphorylation in cumulus cells and also did not totally eliminate tyrosine
      phosphorylation in oocytes. However, ROS did inhibit the Phosphoinositide 3
      kinase (PI3) activity when oocytes mature without EGF. Accumulation of Akt/PKB
      (protein kinase B), JNK1/2 (jun N-terminal kinases) and Aurora-A in oocytes
      during maturation was not affected by ROS. However, the phosphorylation of Akt
      but not JNKs was diminished in ROS-treated oocytes. Thus, PI3 kinase/Akt, JNK1/2
      and Aurora-A are likely to be involved in the regulation of bovine oocyte
      maturation and some of these pathways seem to be independent to MPF activity and
      meiotic resumption. This complex regulation may explain the partial meiotic
      arrest of ROS-treated oocytes and the accelerated maturation observed after such
      treatment.

PMID- 15457548
TI  - Maintaining cholesterol homeostasis: sterol regulatory element-binding proteins.
AB  - The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has
      become much more transparent with the discovery of sterol regulatory element
      binding proteins (SREBPs) in recent years. These membrane proteins are members of
      the basic helix-loop-helix-leucine zipper (bHLH-Zip) family of transcription
      factors. They activate the expression of at least 30 genes involved in the
      synthesis of cholesterol and lipids. SREBPs are synthesized as precursor proteins
      in the endoplasmic reticulum (ER), where they form a complex with another
      protein, SREBP cleavage activating protein (SCAP). The SCAP molecule contains a
      sterol sensory domain. In the presence of high cellular sterol concentrations
      SCAP confines SREBP to the ER. With low cellular concentrations, SCAP escorts
      SREBP to activation in the Golgi. There, SREBP undergoes two proteolytic cleavage
      steps to release the mature, biologically active transcription factor, nuclear
      SREBP (nSREBP). nSREBP translocates to the nucleus and binds to sterol response
      elements (SRE) in the promoter/enhancer regions of target genes. Additional
      transcription factors are required to activate transcription of these genes.
      Three different SREBPs are known, SREBPs-1a, -1c and -2. SREBP-1a and -1c are
      isoforms produced from a single gene by alternate splicing. SREBP-2 is encoded by
      a different gene and does not display any isoforms. It appears that SREBPs alone,
      in the sequence described above, can exert complete control over cholesterol
      synthesis, whereas many additional factors (hormones, cytokines, etc.) are
      required for complete control of lipid metabolism. Medicinal manipulation of the
      SREBP/SCAP system is expected to prove highly beneficial in the management of
      cholesterol-related disease.

PMID- 15457549
TI  - CDH1 germline mutation in hereditary gastric carcinoma.
AB  - This paper provides a bird's-eye view both in preclinical and clinical aspects of
      E-cadherin germline gene (CDH1) in gastric cancer patients and their families. E
      cadherin, a product of CDH1 gene, belonging to the functionally related trans
      membrane glycoprotein family, is responsible for the Ca(2+)-dependent cell-cell
      adhesion mechanism and contributes to dissociation followed by acquisition of
      cell motility, which usually occurs in the first step of cancer invasion and
      metastasis. CDH1 gene germline mutation is common in many types of carcinoma, and
      occurs very frequent in hereditary gastric carcinoma (HGC) patients and their
      families. Recently, more and more researches support that E-cadherin plays an
      important role in the differentiation, growth and invasion of HGC. So it is of
      great value to clarify its mechanisms both for understanding HGC pathogenesis and
      for clinical therapy, especially in China, where there are a high risk population
      of gastric cancer and a high HGC incidence rate. In this paper, recent researches
      on CDH1 gene mutation, especially its role in tumor genesis and progress of HGC,
      are reviewed, and advances in evaluation of its mutation status for HGC
      diagnosis, therapy and prognosis, are also discussed briefly.

PMID- 15457550
TI  - Expression of survivin in primary and metastatic gastric cancer cells obtained by
      laser capture microdissection.
AB  - AIM: Survivin, a recently identified member of the inhibitor of apoptosis protein
      family, is expressed during development and in various human cancers. However,
      its expression in normal tissues and clinical relevance in cancers are still
      debated. In the present study, we analyzed the expression of the survivin gene in
      human primary and metastatic gastric cancer cells as well as in paired epithelial
      cells from normal gastric mucosa by means of a novel laser capture
      microdissection (LCM) technique coupled with reverse transcription-polymerase
      chain reaction (RT-PCR). METHODS: Thirty patients who had undergone gastrectomy
      with lymph node dissection for gastric cancer without preoperative treatments
      were included. Neoplastic tissue, metastatic lymph nodes, and apparently
      uninvolved normal tissue were collected from each patient. LCM-captured "pure"
      cell groups were respectively subjected to RT-PCR analysis with primers specific
      for the survivin gene. RESULTS: Of the paired samples from 30 gastric cancer
      patients studied, 24 (80%) primary gastric cancer cell groups and 7 (23%)
      adjacent morphologically "normal" gastric epithelial cell groups were shown to
      have a detectable survivin expression. There was a statistically significant
      difference in suvivin expression between these two groups (P<0.01). Meanwhile,
      95% (19/20) of the metastatic gastric cancer cell groups from lymph nodes had a
      clear expression of te survivin gene. However, no significant correlation between
      survivin expression and clinicopathological features of gastric cancer was
      observed in the present study. CONCLUSION: Survivin expression is present in the
      majority of gastric cancer cell groups obtained by LCM techniques. The high
      expression rate in metastatic lesions suggests a possible role of survivin in
      cancer invasiveness and metastasis. It may contribute to the detection of gastric
      cancer micrometastasis as a potential molecular marker. In addition, the high
      expression percentage renders survivin a potential target in the therapy for
      gastric cancer.

PMID- 15457551
TI  - Interferon plus ribavirin and interferon alone in preventing hepatocellular
      carcinoma: a prospective study on patients with HCV related cirrhosis.
AB  - AIM: To determine the role of interferon (IFN) with or without ribavirin in
      preventing or delaying hepatocellular carcinoma (HCC) development in patients
      with hepatitis C virus (HCV) related cirrhosis. Data on the preventive effect of
      IFN plus ribavirin treatment are lacking. METHODS: A total of 101 patients (62
      males and 39 females, mean age 55.1+/-1.4 years) with histologically proven HCV
      related liver cirrhosis plus compatible biochemistry and ultrasonography were
      enrolled in the study. Biochemistry and ultrasonography were performed every 6
      mo. Ultrasound guided liver biopsy was performed on all detected focal lesions.
      Follow-up lasted for 5 years. Cellular proliferation, evaluated by measuring Ag
      NOR proteins in hepatocytes nuclei, was expressed as AgNOR-Proliferative index
      (AgNOR-PI) (cut-off = 2.5). Forty-one patients (27 males, 14 females) were only
      followed up after the end of an yearly treatment with IFN-alpha2b (old treatment
      control group = OTCG). Sixty naive patients were stratified according to sex and
      AgNOR-PI and then randomized in two groups: 30 were treated with IFN-alpha2b +
      ribavirin (treatment group = TG), the remaining were not treated (control group =
      CG). Nonresponders (NR) or relapsers in the TG received further IFN/ribavirin
      treatments after a 6 mo of withdrawal. RESULTS: AgNOR-PI was significantly
      lowered by IFN (P<0.001). HCC incidence was higher in patients with AgNOR-PI>2.5
      (26% vs 3%, P<0.01). Two NR in the OTCG, none in the TG and 9 patients in the CG
      developed HCC during follow-up. The Kaplan-Mayer survival curves showed
      statistically significant differences both between OTCG and CG (P<0.004) and
      between TG and CG (P<0.003). CONCLUSION: IFN/ribavirin treatment associated with
      re-treatment courses of NR seems to produce the best results in terms of HCC
      prevention. AgNOR-PI is a useful marker of possible HCC development.

PMID- 15457552
TI  - Transfection of p27kip1 enhances radiosensitivity induced by 60Co gamma
      irradiation in hepatocellular carcinoma HepG2 cell line.
AB  - AIM: To study the cell cycle alterations of human hepatoma cell line HepG(2) in
      vitro after (60)Co gamma-irradiation and further to examine the mechanisms
      underlying the enhancement of radiosensitivity to gamma-irradiation in HepG(2)
      transiently transfected with wild type p27(kip1). METHODS: The proliferation of
      HepG(2) cells was evaluated with MTT assay, and the cell cycle profile and
      apoptosis were assessed by cell morphology, DNA fragmentation analysis and flow
      cytometry. HepG(2) cells were transfected with p27(kip1) wild type by using
      Lipofectamine (LF2000), and the expression and subcellular localization of
      p27(kip1) in HepG(2) were detected by immunocytochemistry. RESULTS: (60)Co gamma
      irradiation inhibited the growth of HepG(2) cells in a dose-dependent manner.
      Apoptosis of HepG(2) cells was induced 48 h after gamma ray exposure. Furthermore
      research was carried out to induce exogenous expression of p27(kip1) in HepG(2).
      The expression of p27(kip1) induced G(0)/G(1) phase arrest in HepG(2) cells. The
      overexpression of p27(kip1) enhanced (60)Co gamma-irradiation-induced
      radiosensitivity in HepG(2) cells. CONCLUSION: Overexpression of p27(kip1) is a
      rational approach to improve conventional radiotherapy outcomes, which may be a
      possible strategy for human hepatoma therapy.

PMID- 15457553
TI  - Nude mice model of human hepatocellular carcinoma via orthotopic implantation of
      histologically intact tissue.
AB  - AIM: To establish a nude mice model of human hepatocellular carcinoma (HCC) via
      orthotopic implantation of histologically intact tissue, in order to study
      biologic features of HCC in vivo and to direct clinical treatment respectively.
      METHODS: Histologically intact fresh specimens of HCC were orthotopically
      implanted in nude mice (BALB/c, nu/nu). Survival rate and growth curve were
      investigated with B-ultrasound. Morphological characteristics of pathology and
      spontaneous metastatic rates were detected with microscopy. Expression of
      multidrug resistance genes studied with immunohistochemical method and RT-PCR,
      and other biologic features of implanted tumor were observed and compared with
      human HCC specimens. RESULTS: Out of the specimens from two patients with HCC,
      only one specimen survived in nude mice. The orthotopic implantation tumor
      survival rate, spontaneous intrahepatic metastatic rate, pulmonary metastatic
      rate and bone metastases rate were 100%, 75.0%, 37.5% and 37.5% respectively in
      the first passage. AFP was kept on secreting and increasing with the size of the
      tumor. The morphological characteristics and biologic features were similar to
      the donor's, the protein and mRNA of MDR1 and LRP were expressed in tumors of the
      model and the donor, and there was no significant difference between them
      (P>0.05). CONCLUSION: The model of nude mice with orthotopic implantation of
      histologically intact HCC tissue is an ideal model to study biologic features of
      HCC in vivo and to direct clinical treatment.

PMID- 15457554
TI  - Experimental and clinical assessment of percutaneous hepatic quantified ethanol
      injection in treatment of hepatic carcinoma.
AB  - AIM: To detect the relationship between absolute ethanol injection quantity, the
      interval and formation of fibreboard, the curative effect in treatment of
      hepatocarcinoma and to evaluate the clinical application of percutaneous hepatic
      quantified ethanol injection (PHQEI) in treatment of hepatic carcinoma (HCC).
      METHODS: (1) Experimental study: Twenty-four human hepatic carcinoma SMMC-7721
      xenografted nude mice were randomly divided into three groups: group A injected
      with quantified ethanol at short intervals (QESI), group B with quantified
      ethanol at long intervals (QELI) and group C with a small quantity of ethanol at
      long intervals (SQLI). The tumor tissues were sent for patho-histology and
      electron microscopic examinations. The diameters of tumors were measured with
      high frequency ultrasound before and after therapies and tumor growth index (TGI)
      was calculated. (2) Clinical study: Tumors of 122 cases of pathologically proved
      HCC were injected with quantified ethanol guided by ultrasound every 3-5 d 4-10
      times per period of treatment. The quantity of ethanol was calculated according
      to the regressive equations where Y = 2.885X when the mass was < or =5 cm in
      diameter and Y = 1.805X when the mass was >5 cm in diameter (X is the maximal
      diameter of the mass with the unit cm, Y is the ethanol quantity with the unit
      mL). The survival rates of 1, 2, 3 and 4 years and recurrent rates in situ as
      well as dystopia in the liver were calculated. RESULTS: (1) Experimental study:
      TGI of QESI group (0.072+/-0.018) and QELI group (0.094+/-0.028) was apparently
      lower than that of SQLI group (1.982+/-0.482) (P<0.01). TGI of QESI group seemed
      to be lower than that of QELI group, but it was not markedly different (P>0.05)
      between two groups. Severe degeneration and necrosis could be seen in QESI group
      by patho-histology examination. Coagulative necrosis could be seen in most tumors
      of QESI group and there were no residual cancer cells under electronic
      microscope, while the residual cancer and inflammatory cells and fibre tissues
      could be seen around the tumors of QELI group. Infiltration of inflammatory cells
      could be seen and fibre tissues were formed. (2) Clinical study: B mode
      ultrasound showed that 62.5% of tumors shrank after PHQEI. The survival rates of
      1, 2, 3 and 4 years of the group with tumors < or =3 cm in diameter were higher
      than those of the group with tumors >3 cm in diameter. The recurrent rates of
      tumors in situ of the former group were apparently lower than those of the latter
      group. The recurrent rates of tumors in dystopia in the liver of the former group
      were markedly lower than those of the latter group. The 122 cases underwent a
      total of 1221 PEI. There were no complications such as hemorrhage and severe
      heart, liver and kidney functional injuries except for 1 case of melena and 4
      cases of jaundice who recovered after 1-2 wk under common therapies. CONCLUSION:
      The experimental study shows quantified ethanol at intervals of 3-5 d could
      improve the curative effect of hepatocarcinoma. The clinical study shows PHQEI is
      an effective therapeutic method for HCC with few side-effects, and a low-cost.
      The treatment efficacy is more remarkable for tumors < or =3 cm in diameter.

PMID- 15457555
TI  - Multi-phasic CT arterial portography and CT hepatic arteriography improving the
      accuracy of liver cancer detection.
AB  - AIM: To evaluate the value of multi-phasic CT arterial portography (CTAP) and CT
      hepatic arteriography (CTHA) in differential diagnosis of liver diseases, and to
      improve the specificity of CTAP and CTHA for liver cancer detection. METHODS:
      From January 1999 to December 2002, multi-phasic CTAP and CTHA were performed in
      20 patients with suspected liver disease. CT scanning was begun 25 s, 60 s and
      120 s for the early-, late- and delayed-phase CTAP examinations, and 6 sec, 40 s
      and 120 s for the early-, late- and delayed-phase CTHA examinations respectively,
      after a transcatheter arterial injection of non-ionic contrast material. If a
      lesion was diagnosed as a liver cancer, transcatheter hepatic arterial
      chemoembolization (TACE) treatment was performed, and the follow-up CT was
      performed three or four weeks later. RESULTS: All eighteen HCCs in 12 cases were
      shown as nodular enhancement on early-phasic CTHA. The density of the whole tumor
      decreased rapidly on late and delayed phases, and the edge of 12 tumors (12/18)
      remained relatively hyperdense compared with the surrounding liver tissue, and
      demonstrated as rim enhancement. All HCCs were shown as perfusion defect nodules
      on multi-phasic CTAP. Five tumors (5/18) were shown as rim enhancement on delayed
      phasic CTAP. Rim enhancement was shown as 1 to 2-mm-wide irregular, uneven and
      discontinuous circumferential enhancement at late-, and delayed-phase of CTHA or
      CTAP. Five pseudolesions and 4 hemoangiomas were found in multi-phasic CTAP and
      CTHA. No pseudolesions and hemoangiomas were shown as rim enhancement on late- or
      delayed-phasic CTHA and CTAP. CONCLUSION: Multi-phasic CTAP and CTHA could help
      to recognize the false-positive findings in CTAP and CTHA images, and improve the
      accuracy of CTAP and CTHA of liver cancer detection.

PMID- 15457556
TI  - Induction of HSF1 expression is associated with sporadic colorectal cancer.
AB  - AIM: To explore the activation of signal transduction pathways related with the
      carcinogenesis of sporadic colon cancers. METHODS: A gene array monitoring the
      activation of 8 signal transduction pathways (PathwayFinder GEArray) was used to
      screen the differentially expressed genes between colorectal cancer and normal
      colon tissues. The differentially expressed genes were further analyzed by RT
      PCR, using RNA derived from colorectal cancer and normal colon tissue of 35
      patients. RESULTS: The expression of HSF1, HSF27, HSP90 and iNOS was increased in
      colon cancer tissues compared to normal colon tissue using PathwayFinder GEArray.
      The RT-PCR results showed that the expression of HSF1 was increased in 86%
      (30/35) patients and the expression of iNOS was increased in 63% (22/35)
      patients. CONCLUSION: The induction of HSF1 gene expression is associated with
      sporadic colon cancer. HSF1 induces heat shock stress signaling pathway, which
      might play a role in the carcinogenesis of sporadic colorectal cancer.

PMID- 15457557
TI  - An integrated approach to the detection of colorectal cancer utilizing proteomics
      and bioinformatics.
AB  - AIM: To find new potential biomarkers and to establish patterns for early
      detection of colorectal cancer. METHODS: One hundred and eighty-two serum samples
      including 55 from colorectal cancer (CRC) patients, 35 from colorectal adenoma
      (CRA) patients and 92 from healthy persons (HP) were detected by surface-enhanced
      laser desorption/ionization mass spectrometry (SELDI-MS). The data of spectra
      were analyzed by bioinformatics tools like artificial neural network (ANN) and
      support vector machine (SVM). RESULTS: The diagnostic pattern combined with 7
      potential biomarkers could differentiate CRC patients from CRA patients with a
      specificity of 83%, sensitivity of 89% and positive predictive value of 89%. The
      diagnostic pattern combined with 4 potential biomarkers could differentiate CRC
      patients from HP with a specificity of 92%, sensitivity of 89% and positive
      predictive value of 86%. CONCLUSION: The combination of SELDI with bioinformatics
      tools could help find new biomarkers and establish patterns with high sensitivity
      and specificity for the detection of CRC.

PMID- 15457558
TI  - A novel hepatitis B virus genotyping system by using restriction fragment length
      polymorphism patterns of S gene amplicons.
AB  - AIM: Traditional hepatitis B virus (HBV) genotyping methods using restriction
      fragment length polymorphism (RFLP) can reliably identify genotypes A to F. As
      HBV genotypes G and H have been recently identified, this study was to establish
      an accurate and simple genotyping method for all eight HBV genotypes (A to H).
      METHODS: Two hundred and forty HBV small S sequences obtained from GeneBank were
      analysed for restriction enzyme sites that would be genotype-specific.
      Restriction patterns following digestion with restriction enzymes BsrI, StyI,
      DpnI, HpaII, and EaeI, were determined to identify all eight HBV genotypes. Mixed
      genotype infections were confirmed by cloning and further RFLP analysis. RESULTS:
      The new genotyping method could identify HBV genotypes A to H. Genotypes B and C
      could be determined by a single step digestion with BsrI and StyI in parallel.
      This was particularly useful in the Far East where genotypes B and C are
      predominant. Serum samples from 187 Chinese HBV carriers were analysed with this
      genotyping system, and the genotype distribution was 1.1% (2), 51.9% (97), 40.6%
      (76) and 4.8% (9) for genotypes A, B, C, and D, respectively. Mixed genotypes
      were found in only 3 patients (1.6%). Sequence data analysis confirmed the
      validity of this new method. CONCLUSION: This HBV genotyping system can identify
      all eight HBV genotypes. It is accurate and simple, and can be widely used for
      studies on HBV genotyping.

PMID- 15457559
TI  - Antigenic and immunogenic changes due to mutation of s gene of HBV.
AB  - AIM: To investigate the change of immunological characteristics of HBsAg caused
      by the mutation at codon 145 of HBsAg using DNA-based immunization. METHODS:
      Plasmids expressing mutant and wild type envelope antigens were transfected into
      human hepatocellular carcinoma cells via electrotransformation. The antigenicity
      of HBsAg was studied with EIA and immunocytochemical staining. Then plasmids were
      used to immunize 5 C57BL/6 mice. Sera of mice were detected for anti-HBs and anti
      preS2 with ELISA. RESULTS: The mutant HBsAg could be detected by native antibody
      in EIA and immunocytochemical study. But the A((450 nm)) value of the mutant
      HBsAg in the supernatant was apparently lower than that of the wild-type. Both
      mutant and native HBsAg expression plasmid could stimulate a strong humoral
      immune response to HBsAg and preS2 antigen in mice. Protective antibodies against
      HBsAg elicited by the native HBsAg occurred earlier than that elicited by the
      mutant HBsAg about one to two weeks. The occurrence of protective antibodies
      against preS2 antigen was one to two weeks earlier than that of anti-HBs.
      CONCLUSION: The amino acid substitution causes changes of the antigenicity and
      immunogenicity of HBsAg, but mutant HBsAg can still induce a protective humoral
      immune response in mice.

PMID- 15457560
TI  - Replication and gene expression of mutant hepatitis B virus in a transgenic mouse
      containing the complete viral genome with mutant s gene.
AB  - AIM: To establish the transgenic mouse line harbouring complete hepatitis B virus
      (HBV) genome with mutant s gene (adr subtype). METHODS: Transgenic mice were
      generated by microinjecting HBV genome into fertilized eggs. Integration,
      expression, replication of HBV gene and histological changes in transgenic mice
      were estimated by genomic DNA PCR, serum DNA PCR, Southern blot, ELISA, HE
      staining, immunohistochemistry and transmission electron microscopy. Transgenic
      mice with HBsAg positive in serum were bred and analyzed. RESULTS: A total of 288
      eggs survived from microinjections were transplanted into the oviducts of 13
      pseudopregnant mice and 49 pups were produced. Twenty-six mice were identified to
      have the integrated HBV gene. Serum HBsAg and HBeAg were detected in 2 of 43
      mice. HBsAg and HBcAg in cytoplasm or nuclei of hepatocytes were detected in 10
      mice. Founders with HBsAg in serum were named lineages G145R-15 and G145R-18. Of
      the 16 F1 offsprings generated by G145R-15 founder, 12 were positive for HBV
      genome with PCR, 10 were positive for HBsAg and HBcAg with immunohistochemistry
      and 7 were positive for HBsAg and HBeAg with ELISA. Only 1 of 8 F1 offsprings
      generated by G145R-18 founder was survived and it was detected positive for HBV
      genome, HBsAg, HBcAg and HBeAg. Both of the two lineages had some pathological
      characteristics of mild chronic hepatitis B in the liver, such as swelling of
      hepatocytes and focal hepatocellular necrosis and parenchymal lymphomononuclear
      cell infiltrate. CONCLUSION: Transgenic mice harbouring HBV with mutant s gene
      can be generated. The HBV genes are integrated in the transgenic mice genome and
      can be expressed, replicated, packaged and excreted. HBV DNA can be stably
      transmitted in the transgenic mice.

PMID- 15457561
TI  - Possibility of non-invasive diagnosis of gastric mucosal precancerous changes.
AB  - AIM: To assess the possibility of non-invasive screening of atrophic chronic
      gastritis for preventing further development of gastric cancer. METHODS: One
      hundred and seventy-eight consecutive Helicobacter pylori (H pylori)-positive
      dyspeptic patients after detection of serum levels of pepsinogen-1 (PG-1) and
      gastrin-17 (G-17) by enzyme immunoassay were proposed for endoscopy and
      histology. The serologic and morphologic results were compared with estimating
      the sensitivity, specificity and prognostic values of the tests. RESULTS: There
      was statistically significant reverse dependence between the grade of stomach
      mucosal antral or corpus atrophy and the proper decreasing of serum G17 or PG1
      levels. The serologic method was quite sensitive in the diagnosis of non-atrophic
      and severe antral and corpus gastritis. Also, it was characterized by the high
      positive and negative prognostic values. CONCLUSION: Detection of serum G-17 and
      PG1 levels can be offered as the screening tool for atrophic gastritis. The
      positive serologic results require further chromoendoscopy with mucosal biopsy,
      for revealing probable progressing of atrophic process with development of
      intestinal metaplasia, dysplasia or gastric cancer.

PMID- 15457562
TI  - Role of soluble Fas ligand in autoimmune diseases.
AB  - AIM: To investigate the role of soluble Fas ligand in autoimmune diseases.
      METHODS: RT-PCR was performed to amplify sFasL cDNA from the total RNA extracted
      from activated human peripheral blood lymphocytes. DNA fragments were cloned into
      PCR vector. After sequenced, sFasL gene fragments were inserted into pQE-31
      vector and expressed in E. Coli M15 respectively. Proteins were purified through
      affinity chromatography column with ligand of 6XHis tag and identified by SDS
      PAGE and Western blot. Mice were immunized with sFasL protein and specific anti
      serum was harvested 6 wk after immunization. Monoclonal anti-human FasL antibody
      was made from the immunized mice. Serum level of sFasL in different patients was
      detected using anti-FasL antibodies from the immunized mice. RESULTS: The protein
      expressed was 24 ku by SDS-PAGE electrophrosis. The protein was specially bound
      to anti-human FasL antibody by Western blot analysis. The sFasL protein could
      induce Jurket cell apoptosis in vitro. The concentration of serum sFasL in
      patients with autoimmune diseases was higher than that in normal individuals.
      sFasL could reduce arthritis in collagen induced arthritis (CIA) mice model by
      subcutaneous injection. CONCLUSION: sFasL may be involved in either induction of
      apoptosis or autoimmune diseases. Furthermore, sFasL may have potential
      application in treatment of autoimmune diseases.

PMID- 15457563
TI  - Safe time to warm ischemia and posttransplant survival of liver graft from non
      heart-beating donors.
AB  - AIM: To explore the dynamical changes of histology, histochemistry, energy
      metabolism, liver microcirculation, liver function and posttransplant survival of
      liver graft in rats under different warm ischemia times (WIT) and predict the
      maximum limitation of liver graft to warm ischemia. METHODS: According to WIT,
      the rats were randomized into 7 groups, with WIT of 0, 10, 15, 20, 30, 45, 60
      min, respectively. The recovery changes of above-mentioned indices were observed
      or measured after liver transplantation. The graft survival and postoperative
      complications in each subgroup were analyzed. RESULTS: Liver graft injury was
      reversible and gradually resumed normal structure and function after reperfusion
      when WIT was less than 30 min. In terms of graft survival, there was no
      significant difference between subgroups within 30 min WIT. When WIT was
      prolonged to 45 min, the recipients' long-term survival was severely insulted,
      and both function and histological structure of liver graft developed
      irreversible damage when WIT was prolonged to 60 min. CONCLUSION: The present
      study indicates that rat liver graft can be safely subjected to warm ischemia
      within 30 min. The levels of ATP, energy charge, activities of glycogen, enzyme
      histochemistry of liver graft and its recovery potency after reperfusion may
      serve as the important criteria to evaluate the quality of liver graft.

PMID- 15457564
TI  - Protective effects of tumor necrosis factor alpha antibody and ulinastatin on
      liver ischemic reperfusion in rats.
AB  - AIM: To study the protective effects of tumor necrosis factor alpha (TNF alpha)
      antibody and ulinastatin on liver ischemic reperfusion in rats. METHODS: One
      hundred and twenty male SD rats were randomly divided into four groups: normal
      control group, ischemic group, TNF alpha antibody group and TNF alpha antibody +
      ulinastatin group. The animals were killed at 0, 3, 6, 9, 12 h after ischemia for
      60 min and followed by reperfusion. Serum alanine aminotransferase (ALT),
      malondialdehyde (MDA) and liver histopathology were observed. RESULTS: After
      ischemic reperfusion, the serum ALT and MDA were remarkably increased, and the
      hepatic congestion was obvious. Treatment of TNF alpha antibody and ulinastatin
      could significantly decrease serum ALT and MDA levels, and relieve hepatic
      congestion. CONCLUSION: Ulinastatin and TNF alpha antibody can suppress the
      inflammatory reaction induced by hepatic ischemic reperfusion, and have
      protective effects on rat hepatic ischemic reperfusion injury.

PMID- 15457565
TI  - Oral and nasal administration of chicken type II collagen suppresses adjuvant
      arthritis in rats with intestinal lesions induced by meloxicam.
AB  - AIM: To investigate the curative effects of oral and nasal administration of
      chicken type II collagen (CII) on adjuvant arthritis (AA) in rats with meloxicam
      induced intestinal lesions. METHODS: AA model in Sprague-Dawley (SD) rats with or
      without intestinal lesions induced by meloxicam was established and those rats
      were divided randomly into six groups which included AA model, AA
      model+meloxicam, AA model+oral CII, AA model+nasal CII, AA model+ meloxicam+oral
      C II and AA model+meloxicam+nasal CII (n = 12). Rats was treated with meloxicam
      intragastrically for 7 d from d 14 after immunization with complete Freund's
      adjuvant (CFA), and then treated with chicken CII intragastrically or nasally for
      7 d. Histological changes of right hind knees were examined. Hind paw secondary
      swelling and intestinal lesions were evaluated. Synoviocyte proliferation was
      measured by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H tetrazolium
      bromide (MTT) method. Activities of myeloperoxidase (MPO) and diamine oxidase
      (DAO) from supernatants of intestinal homogenates were assayed by
      spectrophotometric analysis. RESULTS: Intragastrical administration of meloxicam
      (1.5 mg/kg) induced multiple intestinal lesions in AA rats. There was a
      significant decrease of intestinal DAO activities in AA+meloxicam group (P<0.01)
      and AA model group (P<0.01) compared with normal group. DAO activities of
      intestinal homogenates in AA+meloxicam group were significantly less than those
      in AA rats (P<0.01). There was a significant increase of intestinal MPO
      activities in AA+meloxicam group compared with normal control (P<0.01). Oral or
      nasal administration of CII (20 microg/kg) could suppress the secondary hind paw
      swelling(P<0.05 for oral CII; P<0.01 for nasal CII), synoviocyte proliferation
      (P<0.01) and histopathological degradation in AA rats, but they had no
      significant effects on DAO and MPO changes. However, oral administration of CII
      (20 microg/kg) showed the limited efficacy on arthritis in AA+meloxicam model and
      the curative effects of nasal CII (20 microg/kg) were shown to be more efficient
      than that of oral CII (20 microg/kg) both in AA model and in AA+meloxicam model
      (P<0.05). CONCLUSION: Oral administration of CII shows the limited efficacy on
      arthritis in AA rats with intestinal lesions, and nasal administration of CII is
      more efficient than oral administration of CII to induce mucosal tolerance in AA
      rats.

PMID- 15457566
TI  - Expansion of endothelial surface by an increase of vessel diameter during tumor
      angiogenesis in experimental and hepatocellular and pancreatic cancer.
AB  - AIM: A low vessel density is a common feature of malignant tumors. We suggested
      that the expansion of vessel diameter might reconstitute the oxygen and
      nutritient's supply in this situation. The aim of the present study was to
      compare the number and diameter of blood vessels in pancreatic and liver
      carcinoma with normal tissue. METHODS: Tumor induction of pancreatic (DSL6A) or
      hepatocellular (Morris-hepatoma) carcinoma was performed in male Lewis
      (pancreatic cancer) and ACI (hepatoma) rats by an orthotopic inoculation of solid
      tumor fragments (pancreatic cancer) or tumor cells (hepatoma). Six weeks
      (pancreatic cancer) or 12 d (hepatoma) after tumor implantation, the tumor
      microvasculature as well as normal pancreatic or liver blood vessels were
      investigated by intravital microscopy. The number of perfused blood vessels in
      tumor and healthy tissue was assessed by computer-assisted image analysis.
      RESULTS: The vessel density in healthy pancreas (565+/-89 n/mm(2)) was
      significantly higher compared to pancreatic cancer (116+/-36 n/mm(2)) (P<0.001).
      Healthy liver showed also a significantly higher vessel density (689+/-36
      n/mm(2)) compared to liver carcinoma (286+/-32 n/mm(2)) (P<0.01). The comparison
      of diameter frequency showed a significant increase of vessel diameter in both
      malignant tumors compared to normal tissue (P<0.05). CONCLUSION: The expansion of
      endothelial cells during tumor angiogenesis is accompanied to a large extent by
      an increase of vessel diameter rather than by formation of new blood vessels.
      This may be a possible adaptive mechanism by which experimental pancreatic and
      hepatocellular cancers expand their endothelial diffusion surface of endothelium
      to compensate for inadequate neoangiogenesis.

PMID- 15457567
TI  - Biliary drainage after laparoscopic choledochotomy.
AB  - AIM: Transcystic biliary decompression (TCBD) has been proposed as an alternative
      to T-tube placement after laparoscopic choledochotomy (LCD). This permits safe
      primary closure of the choledochotomy and eliminates the complications associated
      with T-tubes. TCBD tube has been secured by Roeder knots and transfixation, and
      removed later than 3 wk after surgery. We presented a modified TCBD (mTCBD)
      method after LCD using the ureteral catheter and the Lapro-Clip (David and Geck,
      Danbury, Connecticut, USA), and compared it with T-tube drainage. METHODS:
      Between October 2002 and June 2003, patients with choledocholithiasis undergoing
      LCD with mTCBD (mTCBD Group, n = 30) were retrospectively compared to those
      undergoing LCD with T-tube drainage (T-tube Group, n = 52) at a single
      institution. RESULTS: There were no significant differences in operative time and
      retained stones between the two groups. Patients in mTCBD group had a
      significantly decreased average output of bile compared with those in T-tube
      group (306+/-141 vs 409+/-243 mL/24 h, P = 0.000). Removal of drain tubes in
      mTCBD group was done significantly earlier than that in T-tube group (median, 5
      vs 29 d, P = 0.000). No complication related to drain tubes was found in mTCBD
      group, and morbidity rate with the T-tube was significantly higher (11.5%), and
      bile leakage following T-tube removal was 5.8%. CONCLUSION: A modified TCBD after
      LCD is safe, effective and easy to perform. It may reduce postoperative
      complications, especially bile leakage.

PMID- 15457568
TI  - Lack of association between seroprevalence of Helicobacter pylori infection and
      primary biliary cirrhosis.
AB  - AIM: To determine the association between seroprevalence of Helicobacter pylori
      (H pylori) infection and primary biliary cirrhosis (PBC). METHODS: In this case
      control study, 149 consecutive patients (10 males, 139 females, mean age 58.2+/
      11 years, range 26-82 years) suffering from PBC and 619 consecutive healthy
      volunteer blood donors (523 males, 96 females, mean age 47+/-5.3 years, range 18
      65 years) attending the Hospital Blood Bank and residing in the same area were
      recruited. A commercial enzyme linked immunosorbent assay was used to detect anti
      H pylori (IgG) antibodies in serum. RESULTS: Antibodies to H pylori were present
      in 78 (52.3%) out of 149 PBC-patients and in 291 (47%) out of 619 volunteers (P =
      0.24, OR 1.24, 95% CI 0.85-1.80). In the subjects less than 60 years old, the
      prevalence of H pylori infection among PBC-patients (40/79) was slightly higher
      than in controls (50.6% vs 46.2%) P = 0.46, OR = 1.19, 95% CI: 0.72-1.95). In
      those over 60 years, the prevalence of H pylori infection was similar between PBC
      patients and controls (54.2% vs 57.8%, P = 0.7, OR 0.86, 95% CI 0.36-2.07).
      CONCLUSION: There is no association between seroprevalence of H pylori infection
      and primary biliary cirrhosis.

PMID- 15457569
TI  - Pathological characteristics of gastric leiomyoblastoma.
AB  - AIM: To determine the pathological characteristics of gastric leiomyoblastoma.
      METHODS: All tissues were obtained during surgery or gastroscopy. Tissue
      specimens for examination by light microscope were 1 cm x 1 cm x 1 cm in size,
      fixed in 40 g/L neutral buffered formaldehyde, embedded in paraffin, and stained
      with hematoxylin and eosin. The fresh tissues obtained for electron microscopy
      were 1 mm x 1 mm x 1 mm in size, and fixed in phosphate buffered 30 g/L
      glutaraldehyde, postfixed in 10 g/L osmium tetroxide and dehydrated in graded
      alcohol, embebbed in Epon 812. Ultrathin sections of 50 nm were stained with
      uranyl acetate and lead citrate and examined under a JEM-2000 EX transmission
      electron microscope. RESULTS: The most important histopathological feature of
      leiomyoblastoma was the predominance of large, rounded or polygonal cells with
      characteristic perinuclear clear zone in cytoplasms. The tumor cells arranged in
      patch, cell junction or junctional complex could be found occasionally between
      cells under electron microscope. Most of the neoplastic cytoplasms were filled
      with myofilaments, dense bodies, and dense patches. Rough endoplasmic reticulum
      dilatated as lakes, and large quantities of protein secretions of intermediate
      electron density were found in the dilated cisternae. Intracisternal segregation
      could also be found. The nuclei were round or oval, and anomalous nuclei were
      found in part of cells. CONCLUSION: The diagnosis of gastric leiomyoblastoma can
      be confirmed by electron microscopy. The clear appearance of tumor cells is due
      to the dilation of rough endoplasmic reticulum, not fat droplets, glycogens or
      mucus in cytoplasm.

PMID- 15457570
TI  - Changes of cytosolic [Ca2+]i in neutrophils in pancreatic microcirculation of
      rats with caerulein-induced acute pancreatitis under fluid shear stress.
AB  - AIM: To investigate the fluid shear stress induced changes of (Ca(2+))i in
      neutrophils in pancreatic microcirculation of experimental acute pancreatitis
      (AP). METHODS: Wistar rats (n = 36) were randomized into three groups. A model of
      AP was established by subcutaneous injection of caerulein. Low-shear 30
      viscometer was used to provide steady fluid shear stress on separated
      neutrophils. The mean fluorescent intensity tested by flow cytometry was used as
      the indication of [Ca(2+)]i quantity. RESULTS: Under steady shear, cytosolic
      [Ca(2+)]i showed biphasic changes. The shear rate changed from low to high,
      [(Ca(2+)]i in different groups decreased slightly and then increased gradually to
      a high level (P<0.05). A close correlation was observed between the cytosolic
      [Ca(2+)]i level and the alteration of fluid shear stress in regional
      microcirculation of AP. CONCLUSION: The increase of [Ca(2+)]i is highly related
      to the activation of neutrophils, which contributes to neutrophil adhesion to
      endothelium in the early phase of AP. The effect of fluid shear stress on
      [Ca(2+)]i may play a crucial role in pancreatic microcirculatory failure of AP.

PMID- 15457571
TI  - Expression of human augmenter of liver regeneration in pichia pastoris yeast and
      its bioactivity in vitro.
AB  - AIM: To construct a yeast expression system of human augmenter of liver
      regeneration (hALR) and to examine its bioactivity in vitro. METHODS: With PCR
      and gene recombination techniques, cDNA of open reading frame of hALR was
      obtained from recombinant plasmid pcDNA3.1-hALR and inserted into plasmid pPIC9.
      The cDNA of hALR from recombinant plasmid pPIC9-hALR demonstrated by sequencing
      was subcloned into plasmid pPIC9K. The recombinant plasmid pPIC9K-hALR was
      transformed into GS115 with electroporation. hALR was expressed by GS115 under
      the induction of 5 mL/L methanol and purified with ultrafiltration after it was
      analyzed by 15% SDS-PAGE and Western blot. The effects of hALR on in vitro
      proliferation of QGY and HepG(2) cells were evaluated by (3)H-TdR methods.
      RESULTS: The correctness and integrity of recombinant plasmids pPIC9-hALR and
      pPIC9K-hALR were identified by restriction digestion, PCR and sequencing methods,
      respectively. hALR as a secretive protein was successfully expressed by GS115.
      Its molecular weight was about 15 ku and the target protein was about 60% of the
      total protein in the supernatant from GS115 with plasmid pPIC9K-hALR. The results
      of Western blot of hALR showed the specific band. The high qualitative hALR was
      obtained through ultrafiltration. hALR could stimulate in vitro proliferation of
      QGY and HepG(2) cells in a dose-dependent manner, but there was a difference in
      reactivity to hALR between QGY and HepG(2). CONCLUSION: The hALR as a secretive
      protein can be successfully expressed by GS115. It may stimulate in vitro
      proliferation of QGY and HepG(2) cells at a dose-dependent manner. But QGY and
      HepG(2) cells have different reactivities to hALR.

PMID- 15457572
TI  - Photocatalytic killing effect of TiO2 nanoparticles on Ls-174-t human colon
      carcinoma cells.
AB  - AIM: To investigate the photocatalytic killing effect of photoexcited TiO(2)
      nanoparticles on human colon carcinoma cell line (Ls-174-t) and to study the
      mechanism underlying the action of photoexcited TiO(2) nanoparticles on malignant
      cells. METHODS: Ls-174-t human colon carcinoma cells were cultured in RPMI 1640
      medium supplemented with 199 mL/L calf serum in a humidified incubator with an
      atmosphere of 50 mL/L CO(2) at 37 degrees C. Viable cells in the samples were
      measured by using the MTT method. A GGZ-300 W high pressure Hg lamp with a
      maximum ultraviolet-A (UVA, 320-400 nm) irradiation peak at 365 nm was used as
      light source in the photocatalytic killing test. RESULTS: The photocatalytic
      killing of Ls-174-t cells was carried out in vitro with TiO(2) nanoparticles. The
      killing effect was weak by using UVA irradiation without TiO(2) nanoparticles. In
      our studies, the photocatalytic killing effect was correlated with the
      concentration of TiO(2) and illumination time. Once TiO(2) was added, Ls-174-t
      cells were killed at a much higher rate. In the presence of 1 000 microg/mL
      TiO(2), 44% of cells were killed after 10 min of UVA irradiation, and 88% of
      cells were killed after 30 min of UVA irradiation. CONCLUSION: When the
      concentration of TiO(2) is below 200 microg/mL, the photocatalytic killing effect
      on human colon carcinoma cells is almost the same as that of UVA irradiation
      alone. When the concentration of TiO(2) is above 200 microg/mL, the remarkable
      killing effect of photoexcited TiO(2) nanoparticles can be found.

PMID- 15457573
TI  - Gene expression profiling in Barrett's esophagus and cardia intestinal
      metaplasia: a comparative analysis using cDNA microarray.
AB  - AIM: To study the difference of gene expression profile changes in Barrett's
      esophagus (BE) and cardia intestinal metaplasia (CIM) and to screen the novel
      genes in the early stage by cDNA microarray. METHODS: cDNA retrotranscribed from
      an equal amount of mRNA from BE and CIM epithelial tissues was labeled with Cy3
      and Cy5 fluorescence as probes. The mixed probe was hybridized with three pieces
      of BiostarH-40 s double dot human whole gene chip. The chips were scanned with a
      ScanArray 4000. The acquired images were analyzed using GenePix Pro 3.0 software.
      RESULTS: A total of 141 genes were screened out that exhibited different
      expression in all three chips. There were 74 upregulated and 67 downregulated
      genes in gene expression profiles of BE which were two times of that in CIM.
      CONCLUSION: There is a difference in gene expression level between BE and CIM
      epithelia. These 141 genes probably relate to the occurrence and development of
      BE and the progression to adenocarcinoma.

PMID- 15457575
TI  - Apoptosis pathway of liver cells in chronic hepatitis.
AB  - AIM: To study the pathway of apoptosis in chronic liver disease and the role of
      mitochondria in programmed cell death. METHODS: Liver biopsy specimens from 72
      cases of chronic hepatitis and 29 cases of post hepatitis cirrhosis were studied.
      The pro-apoptotic protein Fas, FasL, Bax and the anti-apoptotic protein Bcl-2,
      Bcl-x(L), Bcl-2 alpha were studied immunohistochemically by SP method. Specimens
      from 15 cases of chronic hepatitis and post hepatitis cirrhosis were examined for
      their ultramicrostructures with special attention to their mitochondrial changes.
      Specimens from 3 normal adults (demised in traffic accidents) were used as
      control. RESULTS: The expression of proapoptotic proteins (Fas, FasL, Bax) in
      hepatocytes was significantly higher in the chronic hepatitis group than in the
      cirrhosis group (P<0.001). In the study of ultramicrostructure 364 hepatocytes
      were examined, from 12 cases of chronic hepatitis (including 10 mild cases, 1
      moderate case and 1 severe case). Out of 364 hepatocytes 40 (11.0%) hepatocytes
      were found with various kinds of destruction in their mitochondria. Rupture of
      the outer membrane of mitochondria and the leakage of matrix from the
      intermembrane space were definitely demonstrated. The ultramicrostructural
      changes of mitochondria in the chronic hepatitis group were statistically higher
      than that in normal adults control group (chi(2)=4.32, P<0.05). CONCLUSION: The
      result of the study was in support of the current view that the apoptotic process
      in chronic hepatitis patients were largely along the intrinsic pathway
      (mitochondrial pathway), given that the intrinsic and extrinsic pathways could
      interlinked (converged) at some point on their progression, also it is impossible
      at present to exclude the possibility that the two pathways could be chosen by
      hepatocytes in parallel simultaneously.

PMID- 15457574
TI  - Antitumor immunity induced by DNA vaccine encoding alpha-fetoprotein/heat shock
      protein 70.
AB  - AIM: To construct a DNA vaccine encoding human alpha-fetoprotein (hAFP)/heat
      shock protein 70 (HSP70), and to study its ability to induce specific CTL
      response and its protective effect against AFP-expressing tumor. METHODS: A DNA
      vaccine was constructed by combining hAFP gene with HSP70 gene. SP2/0 cells were
      stably transfected with pBBS212-hAFP and pBBS212-hAFP/HSP70 eukaryotic expression
      vectors. Mice were primed and boosted with DNA vaccine hAFP/HSP70 by
      intramuscular injection, whereas plasmid with hAFP or HSP70 was used as controls.
      ELISPOT and ELISA were used to detect IFN-gamma-producing splenocytes and the
      level of serum anti-AFP antibody from immunized mice respectively. In vivo tumor
      challenge was measured to assess the immune effect of the DNA vaccine. RESULTS:
      By DNA vaccine immunization, the results of ELISPOT and ELISA showed that the
      number of IFN-gamma-producing splenocytes and the level of serum anti-AFP
      antibody were significantly higher in rhAFP/HSP70 group than in hAFP and empty
      plasmid groups (95.50+/-10.90 IFN-gamma spots/10(6) cells vs 23.60+/-11.80 IFN
      gamma spots/10(6) cells, 7.17+/-4.24 IFN-gamma spots/10(6) cells, P<0.01;
      126.50+/-8.22 microg/mL vs 51.72+/-3.40 microg/mL, 5.83+/-3.79 microg/mL,
      P<0.01). The tumor volume in rhAFP/HSP70 group was significantly smaller than
      that in pBBS212-hAFP and empty plasmid groups (37.41+/-7.34 mm(3) vs 381.13+/
      15.48 mm(3), 817.51+/-16.25 mm(3), P<0.01). CONCLUSION: Sequential immunization
      with a recombinant DNA vaccine encoding AFP and heat shock protein70 could
      generate effective AFP-specific T cell responses and induce definite antitumor
      effects on AFP-producing tumors, which may be suitable for some clinical testing
      as a vaccine for HCC.

PMID- 15457576
TI  - Cloning and sequence analysis of gene oipA encoding an outer membrane protein of
      human Helicobacter pylori.
AB  - AIM: To construct a recombinant E. coli strain that would highly express the
      proinflammatory outer membrane protein of human Helicobacter pylori (H pylori).
      METHODS: The oipA DNA was amplified by PCR, inserted into pET-32a, and
      transformed into Top10 E. coli strain. This recombinant plasmid of Top10 was sent
      out for nucleotide sequence analysis. Finally this sequence AF479754 was compared
      with HP0638 and JHP0581. RESULTS: The sequence of the aim gene was obtained. It
      had 924 base pairs. The identity was 95.32% against HP0638, 95.02% against
      JHP0581, which was higher than the identity between HP0638 and JHP0581.
      CONCLUSION: Although the aim gene was obtained, but it was different from the
      published sequence of GenBank. It is not clear what makes this difference. Maybe
      it is because different strain was used or because there were some variations. So
      more researches are required to prove it.

PMID- 15457577
TI  - Effect of hepatic glucose production on acute insulin resistance induced by lipid
      infusion in awake rats.
AB  - AIM: To explore the influence of hepatic glucose production on acute insulin
      resistance induced by a lipid infusion in awake rats. METHODS: A
      hyperinsulinaemic-euglycaemic clamp was established in awake chronically
      catheterized rats. Two groups of rats were studied either with a 4-h
      intraarterial infusion of lipid/heparin or saline. Insulin-mediated peripheral
      and hepatic glucose metabolism was assessed by hyperinsulinaemic-euglycaemic
      clamp combined with [3-(3)H]-glucose infusion. RESULTS: During hyperinsulinaemic
      euglycaemic clamp, there was a significant increase in plasma free fatty acid
      (FFA, from 741.9+/-50.6 to 2 346.4+/-238.5 micromol/L, P<0.01) in lipid-infused
      group. The glucose infusion rates (GIR) in the lipid infusion rats, compared to
      control rats, were significantly reduced (200-240 min average: lipid infusion;
      12.6+/-1.5 vs control; 34.0+/-1.6 mg/kg.min, P<0.01), declining to - 35% of the
      corresponding control values during the last time of the clamp (240 min: lipid
      infusion; 12.0+/-1.9 vs control; 34.7+/-1.7 mg/kg.min, P<0.0001). At the end of
      clamp study, the hepatic glucose production (HGP) in control rats was
      significantly suppressed (88%) from 19.0+/-4.5 (basal) to 2.3+/-0.9 mg/kg.min
      (P<0.01). The suppressive effect of insulin on HGP was significantly blunted in
      the lipid-infused rats (200-240 min: from 18.7+/-3.0 to 23.2+/-3.1 mg/kg.min
      (P<0.05). The rate of glucose disappearance (GRd) was a slight decrease in the
      lipid-infused rats compared with controls during the clamp. CONCLUSION: These
      data suggest that lipid infusion could induces suppression of hepatic glucose
      production, impairs the abilities of insulin to suppress lipolysis and mediate
      glucose utilization in peripheral tissue. Therefore, we conclude that lipid
      infusion induces an acute insulin resistance in vivo.

PMID- 15457578
TI  - Chronic gastritis rat model and role of inducing factors.
AB  - AIM: To establish an experimental animal model of chronic gastritis in a short
      term and to investigate the effects of several potential inflammation-inducing
      factors on rat gastric mucosa. METHODS: Twenty-four healthy, male SD rats were
      treated with intragastric administration of 600 mL/L alcohol, 20 mmol/L sodium
      deoxycholate and 0.5 g/L ammonia (factor A), forage containing low levels of
      vitamins (factor B), and/or indomethacin (factor C), according to an L(8) (2(7))
      orthogonal design. After 12 wk, gastric antral and body mucosae were
      pathologically examined. RESULTS: Chronic gastritis model was successfully
      induced in rats treated with factor A for 12 wk. After the treatment of animals,
      the gastric mucosal inflammation was significantly different from that in
      controls, and the number of pyloric glands at antrum and parietal cells at body
      were obviously reduced (P<0.01). Indomethacin induced gastritis but without
      atrophy, and short-term vitamin deficiency failed to induce chronic gastritis and
      gastric atrophy. In addition, indomethacin and vitamin deficiency had no
      synergistic effect in inducing gastritis with the factor A. No atypical
      hyperplasia and intestinal metaplasia in the gastric antrum and body were
      observed in all rats studied. CONCLUSION: Combined intragastric administration of
      600 mL/L alcohol, 20 mmol/L sodium deoxycholate and 0.5 g/L ammonia induces
      chronic gastritis and gastric atrophy in rats. Indomethacin induces chronic
      gastritis only. The long-term roles of these factors in gastric inflammation and
      carcinogenesis need to be further elucidated.

PMID- 15457579
TI  - Effect of hepatitis B immunoglobulin on interruption of HBV intrauterine
      infection.
AB  - AIM: To evaluate the efficacy of hepatitis B immunoglobulin (HBIG) in
      interrupting hepatitis B virus (HBV) intrauterine infection during late
      pregnancy. METHODS: We allocated 112 HBsAg positive pregnant women into 2 groups
      randomly. Fifty seven cases in the HBIG group received 200 IU (unit) HBIG
      intramuscularly every 4 wk from the 28 wk of gestation to the time of delivery,
      while 55 cases in the control group received no special treatment. HBsAg, HBeAg,
      HBcAb, HBeAb, HBsAb and HBV DNA levels were tested in the peripheral blood
      specimens from all of the mothers at 28 wk of gestation, just before delivery,
      and in blood from their newborns within 24 h before administration of immune
      prophylaxis. RESULTS: The intrauterine infection rate in HBIG group and control
      group were 10.5% and 27.3%, respectively, with significant difference (P<0.05).
      It showed ascendant trend as HBV DNA levels in the peripheral blood increased
      before delivery. CONCLUSION: HBIG is potent to cut down HBV intrauterine
      infection rate significantly when administered to pregnant women regularly during
      late pregnancy. The possibility of HBV intrauterine infection increases if
      maternal blood HBV DNA> or =10(8) copies/mL.

PMID- 15457580
TI  - Mad2 and p27 expression profiles in colorectal cancer and its clinical
      significance.
AB  - AIM: To investigate the expression of tumor suppressor gene p27 and spindle
      checkpoint gene Mad2 and to demonstrate their expression difference in colorectal
      cancer and normal mucosa and to evaluate its clinical significance. METHODS:
      Immunohistochemical staining was used for detection of expression of Mad2 and p27
      in colorectal cancer and its corresponding normal mucosa. RESULTS: Mad2 was
      significantly overexpressed in colorectal cancer compared with corresponding
      normal mucosa (P<0.01, chi(2) = 7.5), and it was related to the differentiation
      of adenocarcinoma, lymph node metastasis and survival period after excision
      (P<0.05, chi(2) = 7.72, chi(2) = 4.302, chi(2) = 6.234). The rate of p27 positive
      expression in adenocarcinomas and normal mucosa was 40% and 80% respectively.
      There was a significant difference in p27 expression between adenocarcinomas and
      normal mucosa (P<0.001, chi(2) = 13.333), which was related to the
      differentiation degree of adenoca rcinoma and lymph node metastasis (P<0.05,
      chi(2) = 8.901 chi(2) = 4). The positive expression of p27 was not correlated
      with survival period after excision. CONCLUSION: Defect of spindle checkpoint
      gene Mad2 and mutation of p27 gene are involved mainly in colorectal
      carcinogenesis and associated with prognosis of colorectal cancer.

PMID- 15457581
TI  - Effects of intestinal lymph on expression of neutrophil adhesion factors and lung
      injury after trauma-induced shock.
AB  - AIM: To study how intestinal lymph after trauma-induced shock (TIS) interferes
      with expression of neutrophil adhesion factors (CD11b and CD18) and causes lung
      injury. METHODS: Thirty-two adult healthy Sprague-Dawley rats were randomly
      divided into four experimental groups. Groups 1 and 2 included rats with TIS
      caused by hitting the mid-upper part of both side femoral bones with a 2,500 kg
      raw- iron, and with or without ligation of mesenteric lymph duct. Groups 3 and 4
      included rats with sham-TIS and with or without ligation of mesenteric lymph
      duct. Expression of neutrophil CD18 and CD11b in at 1 and 3 h after a 90-min
      TIS/sham-TIS was evaluated. These rats were killed at 3 h after TIS/sham-TIS, and
      lungs were taken immediately. The main lung injury indexes (the MPO activity and
      lung injury score) were measured. RESULTS: The expressions of CD18 and CD11b at 1
      and 3 h after a 90-min TIS and the main lung injury indexes were significantly
      increased compared with those in the sham-TIS groups (P<0.05). Moreover, at 1 and
      3 h after TIS, the expressions of CD18 (32.12+/-1.25 and 33.46+/-0.98) and CD11b
      (29.56+/-1.35 and 30.56+/-1.85) were significantly decreased in rats with
      ligation of mesenteric lymph duct, compared with those (52.3+/-1.12 and 50.21+/
      1.25, and 42.24+/-1.24 and 42.81+/-1.12, respectively) in those without the
      ligation (all P<0.05). The main lung injury indexes in rats with TIS with
      ligation of mesenteric lymph duct (0.96+/-0.12 and 6.54+/-0.35) were also
      significantly decreased, compared with those (1.56+/-0.21 and 9.56+/-0.23) in
      rats with TIS without the ligation (both P<0.05). However, there was no
      significant difference in expressions of CD18 and CD11b and the main lung injury
      indexes between the two sham-TIS groups. CONCLUSION: Previous ligation of
      mesenteric lymph ducts prevents or alleviates the up-regulated expression of PMN
      CD18 and CD11b and the lung injury induced by TIS. Our findings also indicate
      that neutrophil adhesion molecule activation and lung injury during TIS appear to
      be caused by some factors that are released or produced by post-ischemic
      intestine through the mesenteric lymph pathway.

PMID- 15457582
TI  - Inactivation of PTEN is associated with increased angiogenesis and VEGF
      overexpression in gastric cancer.
AB  - AIM: To investigate the expression of PTEN/MMAC(1)/TEP(1) and vascular
      endothelial growth factor (VEGF), their roles in biologic behavior and
      angiogenesis and their association in gastric cancer. METHODS:
      Immunohistochemical staining was used to evaluate the expression of PTEN, VEGF
      and microvascular density (MVD) on paraffin-embedded sections in 70 patients with
      primary gastric cancer and 24 patients with chronic superficial gastritis (CSG).
      Expression of PTEN, VEGF and MVD were compared with clinicopathological features
      of gastric cancer. The relationship between expression of PTEN, VEGF and MVD as
      well as the relationship between PTEN and VEGF expression in cancer cells were
      investigated. RESULTS: PTEN expression significantly decreased (t = 3.98, P<0.01)
      whereas both VEGF expression and MVD significant increased (t = 4.29 and 4.41,
      respectively, both P<0.01) in gastric cancer group compared with CSG group. PTEN
      expression was significantly down-regulated (t = 1.95,P<0.05) whereas VEGF
      expression (t = 2.37, P<0.05) and MVD (t = 3.28, P<0.01) was significantly up
      regulated in advanced gastric cancer compared with early-stage gastric cancer.
      PTEN expression in gastric cancer showed a negative association with lymph node
      metastasis (t = 3.91, P<0.01), invasion depth (t = 1.95, P<0.05) and age (t =
      4.69, P<0.01). MVD in PTEN-negative gastric cancer was significantly higher than
      that in PTEN-positive gastric cancer (t = 3.69, P<0.01), and there was a negative
      correlation between PTEN expression and MVD (gamma= -0.363, P<0.05). VEGF
      expression was positively associated with invasion depth (especially with serosa
      invasion, t = 4.69, P<0.01), lymph node metastasis (t = 2.31, P<0.05) and TNM
      stage (t = 3.04, P<0.01). MVD in VEGF-positive gastric cancer was significantly
      higher than that in VEGF-negative gastric cancer (t = 4.62, P<0.01), and there
      was a positive correlation between VEGF expression of and MVD (gamma= 0.512,
      P<0.05). VEGF expression in PTEN-negative gastric cancer was significantly
      stronger than that in PTEN-positive gastric cancer (t = 2.61, P<0.05), and there
      was a significantly negative correlation between the expression of VEGF and PTEN
      (gamma= -0.403, P<0.05). CONCLUSION: Our results imply that inactivation of PTEN
      gene and over-expression of VEGF contribute to the neovascularization and
      progression of gastric cancer. PTEN-related angiogenesis might be attributed to
      its up-regulation of VEGF expression. PTEN and VEGF could be used as the markers
      reflecting the biologic behaviors of tumor and viable targets in therapeutic
      approaches to inhibit angiogenesis of gastric cancers.

PMID- 15457583
TI  - Gallbladder motility in patients with hepatic cirrhosis before and after portal
      azygous disconnection.
AB  - AIM: To determine and compare the effect of vagus nerve on gallbladder motility
      in patients with hepatic cirrhosis before and after portal azygous disconnection
      (PAD). METHODS: PAD operation (or Hassab's operation) was performed on 18
      patients with portal hypertension, and anterior and posterior vagal trunks were
      cut. On d 3 before operation and d 10 after operation, (99m)Tc-EHIDA 185 MBq was
      administered intravenously to the patients, and scintigraphy was performed at
      0.25 min/frame. A standard fat meal was administered 30 min after scintigraphy,
      and dynamic imaging was performed 60 min after the fat meal. Following appearance
      of the region of interest (ROI) in gallbladder, the time-activity curve of ROI
      was established. The following seven parameters were used: radioactivity at 30
      min after injection of (99m)Tc-EHIDA (RC 30 min), bile emptying fraction (EF),
      bile emptying period (EP), emptying rate (ER), latent period (LP), latent period
      radiocounting increment (LI), and latent period radiocounting increment rate
      (LR). RESULTS: The RC 30 min decreased significantly after operation, compared
      with that before operation (2 693.6+/- 2 406.9 vs 5 606.8+/-2 625.4, P<0.05). The
      radiocounting of gallbladder increased gradually during LP. LP after operation
      was significantly longer than that before operation (13.36+/-5.92 vs 2.24+/-1.48,
      P<0.01). LI and LR after operation were significantly higher than those before
      operation (2 861.62+/-028.3 vs 331.21+/-421.02, and 113.42+/-49.52 vs 7.57+/
      10.75, respectively, both P<0.01). EP after operation was significantly shorter
      than that before operation (18.5+/-6.3 vs 24.1+/-6.4, P<0.05). EF and ER after
      operation were significantly lower than those before operation (13.1+/-5.4 vs
      32.3+/-16.3, and 0.7+/-0.3 vs 1.4+/-0.8, respectively, both P<0.01). CONCLUSION:
      PAD operation is a good clinical model in studying the effect of vagus on
      gallbladder motility. The gallbladder tension after PAD operation decreases
      significantly during the interdigestive phase. The latent period of gallbladder
      contraction prolongs and the motility weakens apparently after a standard fat
      meal. Human vagus influences the gallbladder motility, and cutting of the nerve
      inhibits the gallbladder motility.

PMID- 15457584
TI  - The first symptom of hyperkalemia is death.

PMID- 15457585
TI  - Syndrome resembling PSP after surgical repair of ascending aorta dissection or
      aneurysm.

PMID- 15457586
TI  - Liver injury associated with the beta-interferons for MS.

PMID- 15457587
TI  - Healthy eating. Quick dinners. Easy and delightful.

PMID- 15457588
TI  - Diabetes care. Defining standards, Part 2.

PMID- 15457589
TI  - Just for teens. Underage drinking.

PMID- 15457590
TI  - Options increase for men with erectile dysfunction.

PMID- 15457591
TI  - Addressing women's sexual problems.

PMID- 15457592
TI  - Talking about sex. Speaking out about sexual problems can help find lasting
      solutions.

PMID- 15457593
TI  - How safe is your food? When it comes to foodborne illnesses, the news is
      decidedly mixed.

PMID- 15457594
TI  - Flavors of India. Prepare the marvelous dishes of India right in your own
      kitchen.

PMID- 15457595
TI  - Research profile. Carbs and fats. How much of each? Bonnie J. Brehm, PhD, RD.

PMID- 15457596
TI  - XV International AIDS Conference: science versus political science.

PMID- 15457597
TI  - Understanding the costs of pharmaceuticals.

PMID- 15457598
TI  - Bridging a gap: surgical management of HIV-associated lipoatrophy.

PMID- 15457599
TI  - Squamous intraepithelial lesion of the anus in a man with HIV infection.

PMID- 15457600
TI  - Prison linked to AIDS in Blacks.

PMID- 15457601
TI  - Treating the latent reservoir of HIV.

PMID- 15457602
TI  - What's next? Treatment options when the first antiretroviral regimen fails
      virologically or is not tolerated, Part 2.
AB  - As outlined in Part 1 of this 2-part review, there are many choices for the
      initial treatment of HIV infection. The Department of Health and Human Services
      HIV treatment guidelines include regimens that are "preferred" or "alternative"
      for initial therapy. In Part 2 of this review, we discuss those regimens that are
      considered alternatives, as well as emerging combinations that may be considered
      for inclusion in future treatment guidelines. With any of these treatments, a
      change in therapy may be required if drug resistance or intolerance occurs. An
      initial regimen is important because of its immediate effects and potential
      influence on the utility of subsequent treatment options. HIV clinicians should
      be aware of the resistance and safety profiles of all of the various regimens
      they may prescribe as initial therapy and should be ready to employ a strategy
      for subsequent treatment in the event of virologic failure or the development of
      drug toxicity. This article builds on Part 1 by suggesting treatment algorithms
      for those experiencing adverse events or the emergence of drug resistance when
      using recommended or common alternative and emerging anti-HIV regimens.

PMID- 15457603
TI  - Deep vein thrombosis after intravenous immunoglobulins associated with
      methylprednisolone.

PMID- 15457604
TI  - A case of acquired von Willebrand syndrome successfully treated with recombinant
      Factor VIIa during thyroidectomy.

PMID- 15457605
TI  - Late coronary thrombosis after drug-eluting stent: stent vs patient-driven
      prescription of aspirin-clopidogrel combination.

PMID- 15457606
TI  - World Health Organization fact sheet. Making pregnancy safer.

PMID- 15457607
TI  - World Health Organization fact sheet. Tuberculosis.

PMID- 15457608
TI  - World Health Organization press release. Drug resistant tuberculosis levels ten
      times higher in Eastern Europe and Central Asia.

PMID- 15457609
TI  - World Health Organization press release. WHO sees surge in progress against
      tuberculosis on eve of global summit.

PMID- 15457610
TI  - Medical devices; clinical chemistry and clinical toxicology devices;
      classification of sirolimus test system devices. Final rule.

PMID- 15457612
TI  - A review of the seventh ASM conference on Candida and Candidiasis, Austin, Texas,
      March 18-22, 2004.

PMID- 15457611
TI  - [Three special cases of pregnancy outcome to reflect about].
AB  - BACKGROUND: Neonatal alloimmune thrombocytopenia (NAITP) may be a serious
      condition with prenatal intracranial haemorrhages. Our three cases of serious
      NAITP raise the question of whether pregnant women should be screened for
      thrombocyte type and then for HPA-1a antibodies if they are HPA-1bb positive.
      CASE REPORTS: We present three cases of severe NAITP in which screening and
      follow up of HPA-1a antibodies prevented serious sequelae in two of the siblings.
      The first child was a stillbirth with congenital hydrocephalus caused by an
      intraventricular haemorrhage. In the second pregnancy, the mother was found to be
      platelet type HPA-1bb with platelet antibodies against HPA-1a. The antibody level
      was extremely high and an elective caesarean section was performed four weeks
      before term. The platelet count at birth was 3 and 5 x 10(9)/L and a transfusion
      of matched platelets was immediately performed followed by infusion of
      intravenous immunoglobulin. In the third pregnancy, an intracerebral haemorrhage
      was detected by ultrasound at 27 weeks of gestation. The mother was given
      steroids to induce foetal lung maturation followed by a caesarean section in week
      28. The platelet count was 6 x 10(9)/L. The child was transfused with compatible
      platelets and given an infusion of intravenous immunoglobulin. OUTCOME: None of
      the two children have developed any psychomotor sequelae by the age of five and
      three years, respectively. The importance of screening for platelet type and anti
      platelet antibodies and mode of delivery is discussed.

PMID- 15457613
TI  - States race to lead stem-cell research.

PMID- 15457614
TI  - In cloning debate, a compromise.

PMID- 15457615
TI  - The 7th Conference on Candida and Candidiasis, Austin, Texas, USA, March 18-22,
      2004.

PMID- 15457616
TI  - The Second International Meeting on Yeast Apoptosis (IMYA 2), Smolenice, Slovak
      Republic, 17-20 September 2003.

PMID- 15457617
TI  - Trials and tribulations: new pressure on drug companies to reveal all about their
      clinical tests.

PMID- 15457618
TI  - Symposium: "Herman Phaff: Learning from Yeast" Santiago de Compostela, Spain, 23
      24 September 2003.

PMID- 15457619
TI  - Ethical dilemmas of Israeli social workers.

PMID- 15457620
TI  - Physiology of Yeasts and Filamentous Fungi II (PYFF-2), Anglet, France, March 24
      28, 2004.

PMID- 15457621
TI  - Cloning, public policy and the Constitution.

PMID- 15457622
TI  - The Academy Colloquium 'Fungal Phylogenomics', Amsterdam, The Netherlands, 11-12
      May, 2004.

PMID- 15457623
TI  - The effect of abortion legalization on sexual behavior: evidence from sexually
      transmitted diseases.
AB  - Unwanted pregnancy represents a major cost of sexual activity. When abortion was
      legalized in a number of states in 1969 and 1970 (and nationally in 1973), this
      cost was reduced. We predict that abortion legalization generated incentives
      leading to an increase in sexual activity, accompanied by an increase in sexually
      transmitted diseases (STDs). Using Centers for Disease Control data on the
      incidence of gonorrhea and syphilis by state, we test the hypothesis that
      abortion legalization led to an increase in sexually transmitted diseases. We
      find that gonorrhea and syphilis incidences are significantly and positively
      correlated with abortion legalization. Further, we find a divergence in STD rates
      among early legalizing states and late legalizing states starting in 1970 and a
      subsequent convergence after the Roe v. Wade decision, indicating that the
      relation between STDs and abortion is casual. Abortion legalization accounts for
      about one-fourth of the average disease incidence.

PMID- 15457624
TI  - South Korea a fertile field for research into cloning.

PMID- 15457625
TI  - North Korea's use of chemical torture alleged.

PMID- 15457626
TI  - Body parts suit enters murky area of the law.

PMID- 15457627
TI  - Court rejects Ashcroft, backs suicide law.

PMID- 15457629
TI  - Genetics guru says infanticide can be moral.

PMID- 15457628
TI  - The bed of life: a discussion of organ donation, its legal and scientific
      history, and a recommended "opt-out" solution to organ scarcity.

PMID- 15457630
TI  - Coroner seeks inquiry into 'mass euthanasia' at hospital.

PMID- 15457631
TI  - Council grants MS sufferer right to choke to death.

PMID- 15457632
TI  - Stem-cell bank opens for research.

PMID- 15457633
TI  - Top scientists want 'cowboy cloning' banned.

PMID- 15457634
TI  - Dying man challenges doctors over right to live.

PMID- 15457635
TI  - Investing in frozen assets--the world's first stem cell bank opened in the UK
      this week and its closely-guarded contents could change our lives. But is the
      vision flawed?

PMID- 15457636
TI  - Lethal injections: the law, science, and politics of syringe access for injection
      drug users.

PMID- 15457637
TI  - Oral & maxillofacial pathology and medicine--a dental specialty issue whose time
      has come?

PMID- 15457639
TI  - Issue dedicated in memoriam to Gabriel Ward.

PMID- 15457640
TI  - Information processing in medical imaging 2003. Proceedings of the 18th
      International Conference. July 2003. Ambleside, United Kingdom.

PMID- 15457641
TI  - Migration of physicians and nurses: a world wide picture. 1978.

PMID- 15457643
TI  - Proceedings of the 11th International Conference on Production Diseases in Farm
      Animals. August 12-16, 2001. Frederiksberg, Denmark.

PMID- 15457642
TI  - [Report on the First World Health Professions Alliance Leadership Symposium &
      Fifty-Seventh World Health Assembly].

PMID- 15457644
TI  - Innovation and drug reimportation: cost, value, and tradeoffs - economic, legal,
      and public policy implications. Proceedings of an University of Michigan Center
      for Medication Use, Policy and Economics symposium. April 18-20, 2004.
      Washington, DC, USA.

PMID- 15457645
TI  - Problem-based learning.
AB  - Problem-based learning has been used in medical school in a number of different
      countries around the world for over 50 years, with both undergraduate and
      graduate students. Instead of the traditional lectures, laboratory practical
      classes and tutorial system of education, students in small groups are presented
      with a problem that they must try to solve. They are assisted by a 'facilitator'
      who helps them formulate the problem and generally advises them but does not
      supply information. The students have to decide what information they need to
      solve the problem, find it and communicate it to the others in the group. At this
      stage a solution may be apparent, but several more group discussions to
      reformulate the problem followed by re-iterations of the information seeking
      process may be needed before a solution can be found. The theory is that because
      information is sought and presented in a relevant context, it is valued and is
      more likely to be remembered. At the end of the session student reflect on how
      they performed. Problem-based learning has been criticised from a number of
      points of view, especially that it does not present a coherent curriculum, the
      curriculum is not necessarily 'covered', and that in many medical schools the
      implementation has been less than optimal.

PMID- 15457647
TI  - Resiting non-draining catheters.

PMID- 15457646
TI  - Resiting non-draining catheters.

PMID- 15457648
TI  - Environmental health.

PMID- 15457649
TI  - The use of patient group directions in the Royal Naval Medical Services.
AB  - As the first primary care nurse practitioner, the author wished to explore the
      future use of Patient Group Directions (PGD's) within the Royal Naval Medical
      Services (RNMS). Extensive investigations carried out within the National Health
      Service (NHS) have resulted in changes in legislation allowing registered nurses
      to supply medications using PGD's. The design and implementation of PGD's require
      a cohesive approach of a doctor or dentist, a pharmacist and the lead health care
      professional. In order that they are implemented in a safe and effective manner
      all concerned parties must undertake a robust education and training programme.
      The RNMS will need to address a number of change management issues in order that
      registered nurses are supported in continuing professional development and PGD's
      are adopted as practice.

PMID- 15457650
TI  - A new era of primary health care at the Maritime Warfare School, HMS Collingwood.

PMID- 15457651
TI  - The first fatal case of capnocytophaga canimorsus sepsis caused by a cat scratch.
AB  - A case is presented of fatal capnocytophaga canimorsus sepsis caused by a
      neglected cat scratch. Although fatalities are known to occur as a result of
      sepsis caused by this organism, death following cat scratch transmission has not
      previously been reported. The case is important as it demonstrates how a
      seemingly innocuous injury can have devastating consequences that may have been
      prevented by simple first aid measures.

PMID- 15457652
TI  - Working abroad as a military trainee.

PMID- 15457653
TI  - Victor Dickins (1838-1915): naval surgeon, barrister, orientalist and university
      administrator.

PMID- 15457654
TI  - A dental hygienist's perspective.

PMID- 15457655
TI  - More on seriousness of animal rights struggle.

PMID- 15457656
TI  - Comments on changes to veterinary education programs.

PMID- 15457657
TI  - More on shelter medicine.

PMID- 15457658
TI  - What is your diagnosis? Gastrointestinal stasis syndrome.

PMID- 15457659
TI  - Anesthesia case of the month. Mallard undergoing phacoemulsification of a
      cataract.

PMID- 15457660
TI  - Energy requirements and body surface area of cats and dogs.

PMID- 15457661
TI  - Dog bites veterinarian: the legal issues.

PMID- 15457662
TI  - Anesthetic indices of sevoflurane and isoflurane in unpremedicated dogs.
AB  - OBJECTIVE: To compare the anesthetic index of sevoflurane with that of isoflurane
      in unpremedicated dogs. DESIGN: Randomized complete-block crossover design.
      ANIMALS: 8 healthy adult dogs. PROCEDURE: Anesthesia was induced by administering
      sevoflurane or isoflurane through a face mask. Time to intubation was recorded.
      After induction of anesthesia, minimal alveolar concentration (MAC) was
      determined with a tail clamp method while dogs were mechanically ventilated.
      Apneic concentration was determined while dogs were breathing spontaneously by
      increasing the anesthetic concentration until dogs became apneic. Anesthetic
      index was calculated as apneic concentration divided by MAC. RESULTS: Anesthetic
      index of sevoflurane (mean +/- SEM, 3.45 +/- 0.22) was significantly higher than
      that of isoflurane (2.61 +/- 0.14). No clinically important differences in heart
      rate; systolic, mean, and diastolic blood pressures; oxygen saturation; and
      respiratory rate were detected when dogs were anesthetized with sevoflurane
      versus isoflurane. There was a significant linear trend toward lower values for
      end-tidal partial pressure of carbon dioxide during anesthesia with sevoflurane,
      compared with isoflurane, at increasing equipotent anesthetic doses. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results suggest that sevoflurane has a higher anesthetic
      index in dogs than isoflurane. Sevoflurane and isoflurane caused similar dose
      related cardiovascular depression, but although both agents caused dose-related
      respiratory depression, sevoflurane caused less respiratory depression at higher
      equipotent anesthetic doses.

PMID- 15457663
TI  - Surgical correction of subaortic stenosis via right ventriculotomy and septal
      resection in a dog.
AB  - After 2 years of medical management with a beta-adrenoreceptor blocking agent, a
      30-month-old castrated male Golden Retriever with subaortic stenosis was treated
      surgically because of progression of its condition. In an attempt to achieve
      complete relief of the left ventricular outflow obstruction, a modified Konno
      procedure consisting of right ventriculotomy and septal myectomy from the
      infundibular portion of the right ventricle was performed; this combination of
      procedures allowed wide resection of the septal portion of the left ventricular
      outflow obstruction. Two years after surgery, the mass of the dog's left
      ventricle had decreased and the peak calculated pressure gradient across the
      aortic valve had decreased to 40 mm Hg, compared with a preoperative value of 240
      mm Hg; at that evaluation, the dog had gained weight and was able to play
      normally. It is suggested that use of this modified approach to the outflow tract
      may have a positive effect on long-term survival time in dogs with subaortic
      stenosis.

PMID- 15457664
TI  - Funduscopic findings following cataract extraction by means of
      phacoemulsification in diabetic dogs: 52 cases (1993-2003).
AB  - OBJECTIVE: To determine prevalence of retinal hemorrhages and microaneurysms in
      dogs with diabetes mellitus following cataract extraction by means of
      phacoemulsification and identify potential risk factors. DESIGN: Retrospective
      study. PROCEDURE: Medical records of dogs undergoing phacoemulsification between
      1993 and 2003 were reviewed, and information was recorded on signalment, history,
      physical examination findings, ophthalmic examination findings, results of
      laboratory testing, electroretinographic findings, and surgical findings.
      Glycemic control was classified as poor, intermediate, or good on the basis of
      baseline blood glucose concentration, perioperative body weight loss, daily
      insulin dosage, and presence of glucosuria and ketonuria. Data from diabetic and
      nondiabetic dogs were analyzed to determine prevalence and risk factors for
      development of retinal hemorrhages or microaneurysms following
      phacoemulsification. RESULTS: 11 of the 52 (21%) dogs with diabetes mellitus
      developed ophthalmoscopic signs of retinal hemorrhages or microaneurysms,
      compared with 1 of the 174 (0.6%) nondiabetic dogs. Median time from onset of
      diabetes mellitus to diagnosis of retinopathy was 1.4 years (range, 0.5 to 3.2
      years). No risk factors for development of retinopathy were identified.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that retinal hemorrhages and
      microaneurysms may be more common and develop earlier in diabetic dogs than
      previously reported. This may affect treatment, as diabetic dogs survive longer
      with improved glycemic control.

PMID- 15457665
TI  - Evaluation of early fetal loss induced by gavage with eastern tent caterpillars
      in pregnant mares.
AB  - OBJECTIVE: To determine whether gavage of pregnant mares (housed without access
      to pasture) with starved eastern tent caterpillars (ETCs) or their excreta is
      associated with early fetal loss (EFL), panophthalmitis, or pericarditis. DESIGN:
      Randomized clinical trial. ANIMALS: 15 mares. PROCEDURE: 15 mares with fetuses
      from 40 to 80 days of gestation (dGa) were randomly assigned to 1 of 3 groups and
      received 2.5 g of ETC excreta, 50 g of starved ETCs, or 500 mL of water,
      respectively, once daily for 10 days. Mares were housed in box stalls, walked
      twice daily, and not allowed access to pasture for 12 days before or during the
      21-day trial. RESULTS: 4 of 5 mares gavaged with starved ETCs (group 2) aborted
      on trial days 8 (2 mares), 10, and 13. No control mares or mares that received
      excreta aborted. Differences between the ETC group and other groups were
      significant. Abortion occurred on 49, 64, 70, and 96 dGa. Allantoic fluids became
      hyperechoic the day before or the day of fetal death. Alpha streptococci were
      recovered from 1 fetus and Serratia marcescens from 3 fetuses. Neither
      panophthalmitis nor pericarditis was seen. The abortifacient component of the
      ETCs was not elucidated. CONCLUSIONS AND CLINICAL RELEVANCE: These findings
      suggest that mares with fetuses from 40 to 120 days of gestation should not be
      exposed to ETCs because they may induce abortion.

PMID- 15457666
TI  - Myonecrosis and cutaneous infarction associated with Salmonella serovar Infantum
      infection in a horse.
AB  - A 5-year-old Quarter Horse mare was referred for evaluation of oral ulcers, limb
      edema, weight loss, and weakness. There was marked diffuse swelling extending
      from the stifle region to the tarsal region of the left hind limb, and the horse
      had a left hind limb lameness. Firm swellings ranging from 2 to 15 cm in diameter
      and consisting of nodules, plaques, and discrete masses were palpated on both
      sides of the neck, over the right shoulder region, over the left elbow region,
      and over the left caudoventral aspect of the abdomen. Laboratory abnormalities
      included hypoproteinemia, neutrophilia, and hyperfibrinogenemia. Results of
      ultrasonographic examination of the left hind limb and masses were suggestive of
      muscle edema, necrosis, and hemorrhage. Histologic examination of a biopsy
      specimen from a subcutaneous mass revealed necrotizing, suppurative myositis. The
      horse's condition gradually deteriorated, and the horse was euthanatized.
      Necropsy revealed myonecrosis, cutaneous infarcts, hepatic abscesses, and
      cholangitis. Salmonella serovar Infantum was cultured from liver and muscle
      lesions, and a diagnosis of Salmonella myonecrosis was made.

PMID- 15457667
TI  - Effect of intranasal vaccination against bovine enteric coronavirus on the
      occurrence of respiratory tract disease in a commercial backgrounding feedlot.
AB  - OBJECTIVE: To measure antibody titers against bovine coronavirus (BCV), determine
      frequency of BCV in nasal swab specimens, and compare calves treated for bovine
      respiratory tract disease (BRD) between those given an intranasally administered
      vaccine and control calves. DESIGN: Randomized clinical trial. ANIMALS: 414
      heifer calves. PROCEDURE: Intranasal BCV antigen concentration and antibody titer
      against BCV were measured on entry to a feedlot. Calves were randomly assigned to
      receive 3.0 mL of a modified-live virus vaccine against bovine enteric
      coronavirus and rotavirus or 3.0 mL of saline (0.9% NaCl) solution. Calves were
      confined to 1 of 2 pens, depending on vaccination status, for a minimum of 17
      days of observation (range, 17 to 99). Selection of calves for treatment of BRD
      and scoring for severity of disease were done by veterinarians unaware of
      treatment status. RESULTS: Intranasal BCV (125/407 [31%]) and serum antibody
      titers > or = 20 against BCV (246/396 [62%]) were identified in calves entering
      the feedlot. Vaccination was associated with significant decrease in risk of
      treatment for BRD; intranasal BCV on entry to the feedlot was associated with
      increased risk of treatment. Univariate analysis revealed that control calves
      with intranasal BRD on entry to the feedlot and those with antibody titer < 20
      were significantly more likely to be treated for BRD. CONCLUSIONS AND CLINICAL
      RELEVANCE: These data provide further evidence of an association between BCV and
      respiratory tract disease in feedlot calves. An intranasally administered vaccine
      appeared to reduce risk of treatment for BRD.

PMID- 15457668
TI  - Pneumothorax in dairy cattle: 30 cases (1990-2003).
AB  - OBJECTIVE: To evaluate the features, underlying causes, results of diagnostic
      testing, and treatment of pneumothorax in dairy cattle. DESIGN: Retrospective
      study. ANIMALS: 30 dairy cattle. PROCEDURE: Medical records of all cattle with a
      diagnosis of pneumonia were reviewed. For cattle with pneumothorax, information
      was obtained pertaining to signalment, anamnesis, diagnosis, treatment, and
      outcome. Survival data were compared between cattle with pneumonia with or
      without pneumothorax. RESULTS: Pneumothorax was associated with bronchopneumonia
      in 18 cattle, interstitial pneumonia in 7 cattle, pharyngeal or laryngeal trauma
      in 3 cattle, and neonatal respiratory distress in 2 calves. Bovine respiratory
      syncytial virus was the most commonly detected infectious agent. Eighteen of 30
      (60%) cattle survived; 8 were euthanatized and 4 died. Survival rate was 81% for
      cattle with pneumonia without pneumothorax during the same time period.
      Pneumothorax was a significant risk factor for failure to survive to discharge
      from the hospital for cattle with underlying chronic bronchopneumonia.
      CONCLUSIONS AND CLINICAL RELEVANCE: Pneumothorax in dairy cattle appears to occur
      most commonly in association with chronic bronchopneumonia. Cattle of both sexes
      and all ages can be affected.

PMID- 15457669
TI  - Quantitative microscopy of human DNA topoisomerase II-alpha expression in
      transitional cell carcinoma of the bladder.
AB  - OBJECTIVE: To compare the nuclear size of various grades of transitional cell
      carcinoma (TCC) stained immunohistochemically with the nuclear enzyme
      topoisomerase II-alpha (topo II-alpha) in bladder urothelial neoplasms. STUDY
      DESIGN: Histologic sections from 53 consecutive papillary bladder neoplasms were
      stained immunohistochemically for topo II-alpha expression. There were 18 (33.9%)
      urothelial neoplasms of low malignant potential (UNLMP), 18 (33.9%) low grade
      urothelial carcinoma (LGUCa), and 17 (32%) with high grade urothelial carcinoma
      (HGUCa). The histologic slides were photographed at 400 x magnification and then
      projected on a screen, and the area with stained nuclei was measured. RESULTS:
      The cells and nuclei in HGUCa were significantly larger than in LGUCa (P < .05)
      and UNLMP (P < .01). CONCLUSION: Calculation of the area fraction of nuclei in
      TCC of the bladder stained with topo II-alpha is an additional method of
      establishing the grade of these tumors.

PMID- 15457670
TI  - Morphometric analysis of AgNORs in thin-layer, liquid-based liver specimens.
AB  - OBJECTIVE: To detect argyrophilic nucleolar organizer regions (AgNORs) in
      ThinPrep (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) liver fine needle
      aspiration (FNA) specimens and to define the diagnostic value of their
      quantitative analysis in the evaluation of hepatic lesions. STUDY DESIGN:
      ThinPrep liquid-based FNA biopsy specimens from 49 malignant and benign liver
      lesions were resampled, fixed in 95% ethanol and stained with the AgNOR technique
      in accordance with the 1-step colloid method. The specimens included 11 benign
      and 38 malignant lesions (23 poorly differentiated hepatocellular carcinomas
      [HCCs] and 15 poorly differentiated metastatic adenocarcinomas [MCs]).
      Morphometric analysis was performed using a Zeiss Axiolab microscope (Carl Zeiss
      GmbH, Jena, Germany) with a mechanical stage fitted with a Sony-iris CCD
      videocamera (Tokyo, Japan). The videocamera was connected to a Pentium III P/C
      (Intel Corp., Santa Clara, California, U.S.A.) loaded with the appropriate image
      analysis software. The measurements were performed with ImageScan software
      (Jandel Scientific, Erkrath, Germany). The number of AgNORs per nucleus (NN) and
      the total area per nucleus occupied by AgNORs (AR) were calculated
      semiautomatically. Statistical analysis was performed using the SPSS software
      package (Chicago, Illinois, U.S.A.). RESULTS: The least significant deviance test
      for multiple comparisons revealed that NN differed significantly between the 3
      groups of samples examined (P < .0001). The mean NN values in HCCs and MCs were
      significantly different (P < .0001). Logistic regression model demonstrated that
      as NN increased, the probability of a MC diagnosis decreased (<4%). AR values
      were different at a statistically significant level only between benign and
      malignant specimens (P = .00006), not between HCCs and MCs (P = .933).
      CONCLUSION: Quantitative analysis of AgNORs in ThinPrep specimens could be a
      diagnostically useful method in liver disease.

PMID- 15457671
TI  - Sampling strategy for prostate tissue microarrays for Ki-67 and androgen receptor
      biomarkers.
AB  - OBJECTIVE: To develop an optimal sampling strategy for tissue microarrays using
      automated digital analysis for androgen receptor (heterogeneous expression) and
      the cellular proliferation marker Ki-67 (homogeneous expression and evaluated by
      others using nonautomated methods). STUDY DESIGN: Tissue microarrays were
      constructed from 23 radical prostatectomy specimens and immunostained for
      androgen receptor expression and cellular proliferation. Automated digital image
      analysis was used, and the minimum number of cores necessary to capture variance
      change <3% was determined. Androgen receptor immunostaining was described by
      percent positive nuclei (PPN) and mean optical density (MOD). RESULTS: Androgen
      receptor PPN variance measurements showed that 5 cores should be obtained when a
      single block of a radical prostatectomy specimen contained cancer. If all of 15
      blocks contained cancer, 2 cores should be obtained from each of 6 blocks. An
      optimal sampling strategy was developed for androgen receptor PPN, androgen
      receptor MOD and Ki-67 PPN. CONCLUSION: The selection of the number of cores to
      sample is a tradeoff between the number of cores available that contain cancer
      and the amount of work involved in the analysis. Sampling no fewer than 5 but no
      more than 12 cores per radical prostatectomy specimen can capture tissue
      heterogeneity.

PMID- 15457672
TI  - Digital image analysis and stereology of angiogenesis in polypoid and nonpolypoid
      colorectal adenomas.
AB  - OBJECTIVE: To evaluate 3-dimensional parameters and bidimensional microvascular
      quantification in the different morphologic presentations of colorectal adenomas.
      STUDY DESIGN: A study was carried out, including 102 neoplastic colorectal
      lesions obtained by endoscopy or surgical resection. For the analysis of
      angiogenesis, immunohistochemistry, digital image analysis, microvascular
      quantification and stereology were used. RESULTS: Microvascular quantification,
      volume and microvascular length estimate rose gradually with high grade dysplasia
      as compared to the low grade ones (P < .001). There was no significant difference
      in angiogenesis between polypoid and nonpolypoid colorectal adenomas in terms of
      quantification and microvascular length estimate. CONCLUSION: The use of digital
      image analysis and stereology added greater objectivity and effectiveness to
      angiogenic evaluation because they allowed accurate segmentation of hypervascular
      areas, representation of the characteristic 3-dimensional morphology of the
      vascular supply and identification of differences in microvascularization in the
      developmental stages of colorectal cancer. However, no significant relation could
      be found between macroscopic type and angiogenesis, suggesting that angiogenesis
      may contribute little to morphogenesis of colorectal adenomas.

PMID- 15457673
TI  - Preneoplastic changes in ovarian tissues.
AB  - OBJECTIVE: To test whether histologically normal epithelium within ovarian
      inclusion cysts and stroma exhibit changes in nuclear chromatin pattern that
      indicate the presence of occult ovarian lesions. STUDY DESIGN: Ovaries were
      collected from 10 low-risk women,from 7 high-risk women and from 3 women with
      ovarian cancer. Histologic sections were cut at 5 microm and hematoxylin and
      eosin stained. High-resolution images were recorded from the epithelium lining
      inclusion cysts and from the underlying stroma of ovaries from these 20 subjects.
      A total of 2860 epithelial nuclei and 3610 stromal nuclei were recorded.
      Karyometric features and nuclear abnormality were computed. Discriminant analyses
      and unsupervised learning algorithms defined deviations from normal that were
      designated "above threshold" and used to compute average nuclear abnormality of a
      second nuclear phenotype. RESULTS: Histologically normal epithelium from
      inclusion cysts of ovaries harboring a malignant lesion was shown to exhibit
      changes in the nuclear chromatin pattern that were statistically significant
      using quantitative image analysis procedures. Similar changes were seen in the
      inclusion cyst epithelia of high-risk ovaries. A subpopulation of cells
      representing a new phenotype was detected in the underlying stroma of women
      harboring a malignant ovarian lesion and in women at high risk of ovarian cancer.
      CONCLUSION: The karyometric changes observed in the epithelia lining inclusion
      cysts and in the underlying stroma of ovaries either with ovarian cancer or at
      high risk of ovarian cancer suggest the presence of preneoplastic changes in
      histologically normal tissue.

PMID- 15457674
TI  - Bone metastases: prognostic applications of cytometric DNA analysis.
AB  - OBJECTIVE: To examine DNA parameters as prognostic factors for developing
      metastases. STUDY DESIGN: Image cytometry was used to determine DNA content of 21
      tumors and 28 metastases. DNA ploidy status, 2c deviation index (2cDI) and DNA
      malignancy grade (DNA-MG) (based on the variation of nuclear DNA content of tumor
      cells around the normal DNA [2c] peak) were examined for their prognostic value.
      RESULTS: Twenty of 21 tumors showed aneuploid content, and 1 tumor showed diploid
      DNA content. Twenty-one bone metastases showed aneuploid cells. In 6 cases both
      euploid and aneuploid cells were detected. In 1 metastasis only euploid cells
      were present. DNA-MG was increased in bone metastases (mean, 2.4) as compared to
      the corresponding primary tumor (mean, 2.2) in most of the cases. The mean value
      of the 2cDI was 30.07 in primary tumors and 42.5 in metastases. Twelve bone
      metastases had a higher 5cEE than did the primary tumor. CONCLUSION: Diploid and
      aneuploid cells were able to leave a tumor and establish metastases. DNA-MG and
      2cDI were increased in metastases in comparison with the primary tumor, but even
      tumors with lower DNA-MG had metastatic potential.

PMID- 15457675
TI  - Quantitation of angiogenesis and its correlation with vascular endothelial growth
      factor expression in astrocytic tumors.
AB  - OBJECTIVE: To quantitate tumor angiogenesis by establishing intratumoral
      microvessel density (IMD), to study vascular endothelial growth factor (VEGF)
      expression in different grades of astrocytomas and to correlate VEGF expression
      with tumor angiogenesis. STUDY DESIGN: Forty cases of astrocytic neoplasms (10 of
      each grade) were assessed for tumor angiogenesis and VEGF expression. The
      panendothelial marker CD31 was used to highlight microvessels. Tumor angiogenesis
      was quantitated as IMD count per square millimeter in areas of high vascularity,
      or "hot spots," using an image analyzer. VEGF expression was studied in sections
      of the tumors. IMD counts per square millimeter and VEGF expression were
      correlated with histologic grade. The angiogenic potential of tumors as reflected
      by IMD counts per square millimeter was correlated with the intensity of VEGF
      expression. RESULTS: Vascular proliferation in high grade gliomas was
      significantly higher as compared to that in low grade gliomas. IMD count per
      square millimeter revealed a positive correlation with histologic grade in high
      grade gliomas. Pilocytic astrocytoma and low grade astrocytoma as a group had
      comparable IMD counts per square millimeter. VEGF expression paralleled IMD
      counts in rare high grade gliomas only. CONCLUSION: Malignant progression in
      astrocytoma is heralded and accompanied by increased angiogenesis. VEGF is an
      important angiogenic factor in high grade gliomas since its expression parallels
      the increased IMD counts in these tumors. In contrast, in low grade gliomas,
      angiogenic factors other than VEGF may contribute to vascular proliferation. The
      results emphasize the role of antiangiogenic therapy as an optimal tool in
      therapeutic strategies as they become available.

PMID- 15457676
TI  - Utility of mean nuclear volume in predicting disease-free survival in locally
      advanced invasive cervical squamous cell carcinoma.
AB  - OBJECTIVE: To evaluate mean nuclear volume (MNV) as a prognostic indicator in
      invasive squamous cell carcinoma of the uterine cervix. STUDY DESIGN: Forty-nine
      consecutive cases of invasive squamous cell carcinoma of the cervix diagnosed in
      1995 were analyzed retrospectively for MNV and correlated with outcome at the end
      of a 5-year follow-up period. RESULTS: The average MNV among patients with a 5
      year disease-free survival (DFS) and patients with disease recurrence within the
      same period was 1424.11 microm3 and 1401.49 microm3, respectively (P = .984, Mann
      Whitney test), indicating a poor relationship between MNV and 5-year DFS.
      CONCLUSION: Estimation of MNV alone in cases of invasive squamous cell carcinoma
      of the cervix is not predictive of DFS.

PMID- 15457677
TI  - Analysis of fluorescent MRI contrast agent behavior in the liver and thoracic
      aorta of mice.
AB  - OBJECTIVE: To characterize the behavior of magnetofluorescent products injected
      in mice intravenously. STUDY DESIGN: The magnetic resonance imaging (MRI)
      products were labelled with fluorescent molecules to examine the biodistribution
      process in vivo and observe them at the cellular level by means of confocal
      microscopy. Three-dimensional (3D) sequences of images were obtained by spectral
      analysis of sample preparations in a multiphoton confocal microscope and analyzed
      by the factor analysis of medical image sequence algorithm, which provides factor
      curves. Factor images are the result of image-processing methods that utilize
      information from emission spectra. Preparations are also screened in the counting
      mode to provide fluorescent lifetime imaging microscopy (FLIM) characterizations.
      RESULTS: Factor images and FLIM images can help to analyze MRI targeting inside
      the liver and thoracic aorta of mice. They show positive detection of Fe-Texas
      red and BOPTA-Eu in the liver and positive detection of Fe-Texas red and negative
      detection of BOPTA-Eu inside the thoracic aorta. CONCLUSION: This investigation
      established the utility of fluorescent MRI contrast agents as in vivo staining
      tools for cellular sites.

PMID- 15457678
TI  - Glandular and stromal area in hyperplastic endometrium and carcinoma.

PMID- 15457679
TI  - Potential of 4'-C-substituted nucleosides for the treatment of HIV-1.
AB  - Extensive efforts have been made to identify nucleoside reverse transcriptase
      inhibitors (NRTIs). Eight NRTIs have now been approved for clinical use; however,
      variants of HIV-1 resistant to these antiviral agents have emerged in patients
      even when they are treated with combinations [highly active antiretroviral
      therapy (HAART)]. Thus, the development of novel compounds that are active
      against drug-resistant HIV-1 variants and that prevent or delay the emergence of
      resistant HIV-1 variants is urgently needed. Previously, 4'-C-substituted
      nucleosides (4'-SNs) were designed as new types of NRTIs. They were synthesized
      and examined as potential therapeutic agents against HIV infection. Among them,
      several 4'-substituted-2'-deoxynucleosides (4'-SdNs), especially those that bear
      an ethynyl group, were shown to be active against various laboratory and clinical
      HIV-1 strains including known drug-resistant variants. These results were
      recently reported by our collaborators. In this review, we summarize the design,
      synthesis and demonstrations of the anti-HIV activity of 4'-SNs, and then
      consider 4'-SNs as potential therapeutic agents for HIV-1.

PMID- 15457680
TI  - Mutations and polymorphisms associated with antiretroviral drugs in HIV-1C
      infected African patients.
AB  - To detect and characterize polymerase gene (pol) polymorphisms and mutation
      patterns in HIV-1C-infected Batswana patients treated with reverse transcriptase
      inhibitors, samples from AIDS patients treated with highly active antiretroviral
      therapy (HAART) were sequenced for the region encompassing the entire HIV-1
      protease (PR) and the first 335 amino acids of reverse transcriptase (RT).
      Amongst the 16 patients treated with antiretroviral (ARV) drugs, eight started
      HAART regimens containing didanosine, stavudine and nevirapine (ddI/d4T/NVP) or
      efavirenz (EFV) (arm A) while the others started with zidovudine (AZT) and
      lamivudine (3TC) given together as combivir (CBV) with either NVP or EFV as arm
      B. Arm B is the first line regimen currently provided by the Botswana ARV
      national programme. Greater efficacy, in terms of treatment duration, was
      observed in patients in arm B (14 months) as compared with patients in arm A (9
      months); P<0.05, n=8. Appearance of the M184V mutation in the arm B patients
      coincided with a rebound of viral load (VL) (4.3 +/-0.1 log10 RNA copies/ml) and
      a significantly improved immunological parameter (deltaCD4=207.0+/-48.1
      cells/microl; P<0.05). Interestingly, patients developing the M184V mutation
      preferentially harboured polymorphisms Q174K and/or I178L located in close
      proximity to pol position 184. The M184V mutation occurred following a clear
      clinical benefit consisting of increased CD4 cell counts and lower plasma viral
      loads. Primary mutations known to be associated with NNRTI and NRTI resistance
      for HIV-1B were observed in 10 of the 16 treated patients.

PMID- 15457681
TI  - Isothiazole derivatives as novel HIV replication inhibitors.
AB  - A series of 3,4,5-trisubstituted isothiazoles has been screened against HIV-1
      (IIIB) and HIV-2 (ROD) at sub-toxic concentrations in acutely infected MT-4
      cells. Among the tested compounds, only 3-mercapto-5-phenyl-4
      isothiazolecarbonitrile was found to inhibit the replication of HIV-1 (IIIB) and
      HIV-2 (ROD) at 50% effective concentrations (EC50) of 7.8 and 9.7 microg/ml,
      respectively. The presence of a thioalkyl chain or dialkylamino function in the 3
      position caused a loss of anti-HIV activity. New 4-cyano-5-phenylisothiazoles
      with other substituents in the 3-position have also been synthesized and studied
      as potential anti-HIV agents. Our results have demonstrated that 5-phenyl-3-(4
      cyano-5-phenylisothiazol-3-yl) disulphanyl-4-isothiazolecarbonitrile and S-(4
      cyano-5-phenylisothiazol-3-yl)-O-ethyl thiocarbonate are effective against both
      HIV-1 (IIIB) (EC50=13.6 and 15.2 microg/ml, respectively) and HIV-2 (ROD)
      (EC50=17.4 and 13.4 microg/ml, respectively).

PMID- 15457682
TI  - Mechanisms of HIV receptor and co-receptor down-regulation by prostratin: role of
      conventional and novel PKC isoforms.
AB  - Prostratin is an unusual non-tumour promoting phorbol ester with potential as an
      inductive adjuvant therapy for highly active antiretroviral therapy (HAART) due
      to its ability to up-regulate viral expression from latent provirus. In addition,
      prostratin is also able to inhibit de novo HIV infection most probably because it
      induces down-regulation of HIV receptors from the surface of target cells. In
      this study, we investigate the mechanisms by which prostratin down-regulates HIV
      receptor and co-receptor surface expression in lymphocytic and monocytic cell
      lines. Our results indicate that prostratin induces down-regulation of surface
      expression of CD4 and CXCR4, but not CCR5, in various cell lines. Down-regulation
      of CD4 and CXCR4 by prostratin is achieved by internalization through receptor
      mediated endocytosis and/or macropinocytosis, which is then followed by
      degradation of these molecules. Because prostratin is a protein kinase C (PKC)
      activator, we next examined the potential contribution of distinct PKC isoforms
      to down-regulate CD4 and CXCR4 in response to prostratin stimulation. Although
      exposure of cells to prostratin or phorbol-myristate-acetate (PMA) induces the
      translocation of several PKC isoforms to the plasma membrane, the use of specific
      PKC inhibitors revealed that novel PKCs are the main mediators of the prostratin
      induced CD4 down-regulation, whereas both conventional and novel PKCs contribute
      to CXCR4 down-regulation. Altogether these results showed that prostratin,
      through the activation of conventional and/or novel PKC isoforms, rapidly reduces
      cell surface expression of CD4 and CXCR4, but not CCR5, by inducing their
      internalization and degradation.

PMID- 15457683
TI  - The effects of exposure to intense, 24 h light on the development of scoliosis in
      young chickens.
AB  - The aetiology of adolescent 5 coliosis remains unknown and hindering research is
      the absence of an appropriate animal model. It is now well-established that
      pinealectomy in young chickens results in the development of scoliosis that has
      many of the characteristics seen in patients with adolescent idiopathic scoliosis
      but the mechanism underlying this phenomenon remains elusive. The principle
      product of the pineal gland is melatonin and so many studies have focused on
      studying the effects of reduced levels of this hormone. The results have been
      mixed and the role of melatonin remains unclear. As melatonin production is
      inhibited by light, it was hypothesised that providing the chickens with an
      environment consisting of intense, continuous light would reduce serum melatonin
      levels and avoid any of the potential artifacts involved with the pinealectomy
      surgery. Consequently, pinealectomised and normal chickens were exposed to very
      intense light for complete 24 h in each day. At the end of 22 days in this
      environment serum melatonin levels had been reduced to very low levels in all
      chickens. Most importantly, 15% of the normal chickens had developed scoliosis
      and the number of pinealectomised chickens that developed scoliosis increased
      from 50% to 80%. The results showed that a method for reducing serum melatonin
      without pinealectomy has been established and which can be used in further
      experiments. Furthermore, the results also showed that reduced levels of serum
      melatonin has significant effects on the development of scoliosis. The indication
      is that there is a threshold level of serum melatonin below which scoliosis may
      develop probably in conjunction with some other factor which has yet to be
      identified.

PMID- 15457684
TI  - Is the labyrinthine dysfunction a causative factor in idiopathic scoliosis?
AB  - The cause of idiopathic scoliosis remains unknown, although research has possibly
      eliminated some hypothetical causes. Recent reports associating scoliosis
      convexity with equilibrium control central processing and motor lateralization
      have suggested that idiopathic scoliosis is connected causally with the motor
      cortex. In order to analyze these factors a study of labyrinthine function was
      carried out. This study included seventeen female patients 12 to 14 years old
      (mean age= 13.36y) with right thoracic idiopathic scoliosis and twelve normal
      control females 12 to 14 years old (mean age =13.1y). An electro-nystagmographic
      study of labyrinthine function (potential nystagmus) was performed in all the
      patients of the study with caloric tests. The nystagmus was recorded with the
      electronystagmographic technique (ENG) using Hartmann device. We evaluate these
      parameters: Slow phase velocity (SPV), Total amplitude (Tamp), Frequency of
      nystagmus (Freq). No children of the study presented spontaneous nystagmus. No
      correlation was found between the convexity of the curvature and the direction of
      nystagmus in posture tests. There were no significant differences between left-
      and right- beating nystagmus. The results are discussed with special reference to
      aetiology in idiopathic scoliosis.

PMID- 15457685
TI  - Is the central nervous system a causative factor in idiopathic scoliosis?
AB  - The present study was designed to investigate the involvement of central nervous
      system (CNS) in the pathogenesis of idiopathic scoliosis. Seventeen female
      patients with right thoracic idiopathic scoliosis (mean age = 13.36y) and ten
      normal controls (mean age =12.6y) entered the study. Magnetic stimulation of the
      brain was performed. Threshold measurements included upper (UT) and lower
      threshold (LT). Cortical latencies of MEPs during muscle activation were also
      measured.

PMID- 15457686
TI  - The NOTOM hypothesis for idiopathic scoliosis: is it nullified by the delayed
      puberty of female rhythmic gymnasts and ballet dancers with scoliosis?
AB  - Nachemson suggested that there are more girls than boys with progressive
      adolescent idiopathic because of a different timing between skeletal maturation
      and postural maturation in the sexes during adolescence. We termed Nachemson's
      concept the neuro-osseous timing of maturation (NOTOM) hypothesis and used it to
      propose a possible medical treatment for idiopathic scoliosis by delaying puberty
      through the pituitary using gonadorelin analogues as in idiopathic precocious
      puberty. The prevalence of scoliosis is reported to be increased in rhythmic
      gymnasts (RGs) in Bulgaria and in ballet dancers (BDs) in the USA. Both groups
      exhibit delayed puberty, which, at first sight, nullifies the NOTOM hypothesis
      for idiopathic scoliosis. While constitutional and environmental factors may
      determine these scolioses, the different curve types in RGs and BDs suggest that
      the exercise pattern over many years determines which type of scoliosis develops,
      although not the curve severity. We support the view that scoliotic RGs should be
      included in a group of sports-associated scoliosis separate from idiopathic
      scoliosis. Hence the delayed puberty of RGs and BDs with scoliosis does not
      nullify the NOTOM hypothesis as their scolioses are not idiopathic. There is a
      need to focus research on such subjects who have defined constitutional and
      environmental factors related to their scolioses.

PMID- 15457687
TI  - Etiologic theories of idiopathic scoliosis: neurodevelopmental concepts to be
      evaluated.
AB  - There is increasing interest in the concept that neuromuscular mechanisms and the
      central nervous system (CNS) are somehow involved in the etiology and
      pathogenesis of idiopathic scoliosis (IS). Yet in the extensive neuroscience
      research of idiopathic scoliosis certain neurodevelopmental concepts have been
      neglected. These include: (1) a CNS body schema for posture and movement control
      generated during development and growth by establishing a long-lasting memory;
      (2) pruning of cortical synapses at puberty; and (3) neuromorphic engineering.
      Memory of developing posture and movement might be established in neurons of the
      CNS body schema in the form of novel proteins; these could be coded by modified
      genes obtained by the recombination (crossing over) of DNA in a similar way to
      that in the production of immunological antibodies and during meiosis. These
      concepts need evaluation in relation to (1) the etiopathogenesis of IS and (2) a
      possible new treatment approach to idiopathic scoliosis involving a neuromorphic
      device to control the output for muscle stimulators that are inserted and driven
      with telemetry.

PMID- 15457688
TI  - Study of the rib cage deformity in children with 10 degrees-20 degrees of Cobb
      angle late onset idiopathic scoliosis, using rib-vertebra angles--aetiologic
      implications.
AB  - The aim of the study is to compare the rib-vertebra angles (RVAs) between
      children with 10 degrees - 20 degrees of Cobb angle late onset idiopathic
      scoliosis (LOIS) and non-scoliotic children. MATERIALS AND METHOD: The RVAs of 47
      children, with mean age 12.4 years, who presented LOIS with a Cobb angle 10
      degrees - 20 degrees, were studied. The children were classified into three
      groups according to the site of the scoliotic curve: 17 children had thoracic
      (T), 14 children had thoracolumbar (TL) and 16 children had lumbar (L) curves.
      The RVAs of the scoliotic children were compared to the RVAs of 60 non-scoliotic
      children of a similar age group, who were studied in the past. RESULTS: The
      comparison of the right and left RVAs within each group showed that the children
      who had: T curves differ at the level T4, T5, T6, T7 and T8, TL curves differ at
      the level T3, and L curves differ at the level T7 and T12. The comparison of the
      ipsilateral RVA's between the scoliotic groups showed that between: T and TL
      curves there are no differences at any thoracic level, between T and L curves the
      RVAs differ at the T7 level on the right side, whereas there are no differences
      between the RVAs on the left side, between TL and L curves the RVAs differ at the
      level T5, T6, and T7 on the right and at the level T5 on the left side. Comparing
      the RVAs between the scoliotic and nonscoliotic children, it was apparent that
      the scoliotic children rib cage had lower RVAs (p<0.01) at almost all thoracic
      levels. DISCUSSION: It has been reported that RVAs is an expression of the
      resultant muscle forces, which act on each rib. It was also suggested that RVA
      asymmetries by weakening the spinal rotation-defending system are aetiological
      for idiopathic scoliosis, (Burwell et al 1992). This study shows that scoliotic
      children with small curves have underdeveloped thoracic cage compared to
      nonscoliotic counterparts. The differences are more apparent in the scoliotic
      children with thoracic curves. It is suggested that the differences of the RVAs
      between right and left side in this group are an expression of asymmetric muscle
      forces acting on the thoracic cage. It is concluded that asymmetric muscle forces
      participate in the pathogenesis of idiopathic scoliosis on the thoracic cage,
      which deforms early.

PMID- 15457689
TI  - Lateral spinal profile in school-screening referrals with and without late onset
      idiopathic scoliosis 10 degrees-20 degrees.
AB  - INTRODUCTION: The aim of this report is a) to study the lateral spinal profile,
      (LSP), in school-screening referrals with and without late onset idiopathic
      scoliosis of small curves 10 degrees - 20 degrees Cobb angle and b) to validate
      LSP's aetiological importance in idiopathic scoliosis pathobiomechanics. METHODS
      AND MATERIAL: The spinal radiographs of 133 children, 47 boys and 86 girls with a
      mean age of 13.28 and 13.39 years respectively and Axial Trunk Inclination (ATI)
      > or = 7 degrees, were examined. The Cobb angle was appraised from the
      anteroposterior standing radiographs and the segmental spinal profile was
      assessed. A line was drawn down the posterior surface of each vertebral body from
      T1 to L5 on lateral standing radiographs, and the angle of this line from the
      vertical was recorded. Intervertebral values for LSP, (ILSP), that is the result
      of the subtraction of two consecutive spinal levels LSP, were also calculated.
      The data were then statistically analyzed. RESULTS: The statistical descriptives
      of LSP and intervertebral LSP are presented for several groups of children,
      namely in those: 1) with straight spines, 2) with spinal curvature having a Cobb
      angle less than 10 degrees, and 3) in scoliotic children with a) thoracic, b)
      thoracolumbar and c) lumbar curves of 10 degrees-20 degrees. A correlation of the
      LSP with Cobb angle for the various types of curves for boys and girls is also
      presented. It is shown that the kyphotic segmental angulation is slightly less
      and the lordotic one almost normal in scoliotics, compared with the values of
      normal children. It is interesting to note that the LSP correlated with Cobb
      angle shows: a) a positive correlation pattern at T6, T7, T8 and T9 for thoracic
      curves of scoliotic boys and b) a negative correlation pattern at T3, T4 and T5
      spinal levels of lumbar curves for scoliotic girls. DISCUSSION: The observed
      differences of the LSP are mainly located at the lumbar spine, suggesting that
      factors acting on the lumbar spine in sagittal plane contribute to the
      development of AIS. The minor hypokyphosis of the thoracic spine and its minimal
      differences observed in the studied small curves with nonscoliotics in this
      report add to the view that the reduced kyphosis, by facilitating axial rotation,
      could be viewed as being permissive, rather than as aetiological, in the
      pathogenesis of idiopathic scoliosis.

PMID- 15457690
TI  - Etiologic theories of idiopathic scoliosis: the apical spinal deformity-
      relevance to surgical practice.
AB  - The current successful management of idiopathic scoliosis is an orthopaedic and
      not a paediatric responsibility. Hence the immediate aim of etiologic research is
      to improve surgical treatments based on a better understanding of the causation
      of the deformity. This focuses attention on the pathomechanisms of the spinal and
      ribcage deformities. The mechanisms of spinal deformity about the apex are
      unresolved but may be caused by forces created in the anterior spinal column.
      Some current theories with practical application involve (1) front-back spinal
      growth mechanisms, (2) rib growth asymmetry and (3) muscles. CONCLUSIONS: The
      application of theory to surgical practice is advanced for concepts of front-back
      spinal growth asymmetry but rib hump reassertion occurs after surgery and these
      concepts ignore the ribcage as a possible factor in scoliosis pathogenesis. A
      theory of ribcage asymmetry involving concave rib overgrowth is beginning to be
      evaluated surgically. After surgery for IIS and AIS reassertion of the deformity
      has been shown to involve preoperative spinal and concave rib factors; the larger
      the concave rib-spinal angle the better results at 2-5 year. Muscular factors
      that may trigger/exacerbate the apical spinal deformity of scoliosis need more
      research. The concept that AIS pathogenesis involves putative neuromuscular
      dysfunction that deforms an immature spine is considered likely by several
      workers.

PMID- 15457691
TI  - Etiology of the so-called "idiopathic scoliosis". Biomechanical explanation of
      spine deformity. Two groups of development of scoliosis. New rehabilitation
      treatment; possibility of prophylactics.
AB  - INTRODUCTION: Between various etiological factors of idiopathic scoliosis we also
      studied the biomechanical causes connected with the hip and pelvic regions. At
      all children with idiopathic scoliosis there is a real or functional abduction
      contracture of the right hip (sometimes plus flexions- and out-rotation
      contracture). The right hip abduction contracture is connected with "syndrome of
      contractures" at newborns and babies. MATERIAL: 629 children treated in
      University Pediatric Orthopaedic Department, Lublin/Poland were divided into two
      groups: *I group of development of scoliosis- 220 children aged from 4 to 10.
      Real abduction contracture of the right hip 4-6-8 degree, adduction of the left
      hip 35-40-45 degree. Rotation deformity, both scoliosis (Lumbar L and thoracic
      Th) at the same time. Progression. **II group of development of scoliosis - 409
      children aged from 10-12 to 14. Adduction of the right hip 10-15 even 20 degrees,
      adduction of the left hip 35-40-45 degree. Lumbar left convex scoliosis, no
      rotation deformity or small, no thoracic scoliosis, or small, no progression or
      small. INFORMATION ABOUT "SYNDROME OF CONTRACTURES": Clinical symptoms of
      _syndrome of contractures" were described exactly by Mau and others. At scoliotic
      patients we see in the region of right hip the following tissues contracted and
      shortened: *tractus iliotibialis, *fascia lata, * fascias of m.gluteus medius and
      minimus, *m. sartorius, *m. rectus, *capsules of right hip joint. CLINICAL
      RESEARCH: Since 1980s we added the tests for the adduction of both hips in
      straight position of the joint to the standard examination of scoliotic patient.
      Depending on the value of adduction movements of both hips we divided all
      patients into two above mentioned groups (I and II). EVALUATION OF PRESENT
      REHABILITATION TREATMENT IN OUR MATERIAL:Children were divided into three groups
      depending on range of scoliosis: A. Scoliosis L 5 degrees - 10 degrees, Th 5
      degrees - 10 degrees. These children did not perform (wrong!) extension exercises
      10% B. Scoliosis L 15 degrees - 25 degrees, Th 15 degrees - 25 degrees. These
      children performed (wrong!) extension exercises 30% C. Scoliosis L 25 degrees -
      35 degrees or more, Th 25 degrees - 35 degrees or more. Older children. Extension
      (wrong!) exercises long time (1-2-3 years!) 60% CONCLUSIONS: 1 . The so-called
      idiopathic scoliosis are connected with the right hip real or functional
      abduction contracture (sometimes plus flexion and out-rotation contracture). 2.
      There are two groups of development of idiopathic scoliosis. The first group -
      small children, early rotation deformity, both scoliosis (L and Th), progression.
      The second group is connected only with the habit of permanent standing "at ease"
      on the right leg. Older children. L scoliosis, sometimes Th scoliosis. 3. X-ray
      pictures of spine with pelvis are necessary for proper diagnosis.4. Abduction
      contracture of the right hip is connected with "syndrome of contractures" of new
      borns and babies.5. We see necessity to introduce new stretching-flexion
      asymmetric exercises and a special sports program for the children endangered
      with scoliosis. 6. We proved that the "new prophylactics" through "new clinical
      test" and "new rehabilitation treatment" at school children (5-6-7-8 years old)
      gives positives results.

PMID- 15457692
TI  - Comparison of body weight and height between normal and scoliotic children.
AB  - AIM: The creation of a database with somatometric parameters (body weight and
      eight) from school screening children and the comparison of nonscoliotic children
      with their counterparts suffering of scoliosis to Cobb angle > or =10 degrees
      curves. MATERIAL AND METHOD: 3631 screened children where divided in 3 groups.
      The 1st group comprised normal children with 0 degrees angle of trunk
      inclination, (ATI). The 2nd group comprised children with ATI > or =1 degree and
      < or = 6 degrees. The third group comprised children with ATI >7 degrees and Cobb
      angle > or =10 degrees. The mean/median and standard deviation (+/- 1 SD) of body
      weight and height, the body mass index (BMI = weight/height2) and the corrected
      for the scoliotic curve height were calculated by age. Statistical analysis
      included descriptives (mean, +/- 1 SD, median) and Mann-Whitney non-parametric
      test. RESULTS: In boys of the 1st and 2nd group 4,25% had obesity (BMI = 30-35),
      2,9% severe obesity (BMI = 30-35) and 1,7% morbid obesity (BMI = 40-45)- while
      6,4%, 1,9% and 1,3% in girls respectively. In the 3rd group girls, 27,2% were
      underweight (BMI = 16-20) and 11,3% severely underweight (BMI < 16), while among
      boys 42% were severely underweight. In the 3rd group there were no obese girls
      and only 5% obese boys. The comparison of body weight between scoliotic (3rd
      group) and nonscoliotic children (1st and 2nd group) fails to show any
      statistical difference. In the 1st and 2nd group, the girls' mean height is
      greater than that of boys aged 9 -12 years but less when boys are 13-18 years
      old. In the 3rd group a mean of 1,15 cm increase is observed after height
      correction for the scoliotic curve, in boys and 1,3 cm in girls respectively. The
      comparison of body height (both uncorrected and corrected) between scoliotic and
      nonscoliotic children fails to show any statistical difference. DISCUSSION
      CONCLUSIONS: A variety of findings regarding the stature and weight of AIS
      children has been published. In this studied Mediterranean sample of the
      population, the somatometric parameters of height and weight in children with
      scoliosis, regardless of curve type and site, are not statistically different
      from their nonscoliotic counterparts.

PMID- 15457693
TI  - Evolution of 3D deformities in adolescents with progressive idiopathic scoliosis.
AB  - The objective of this study was to conduct an intrasubject longitudinal study
      quantifying the evolution of two- and three-dimensional geometrical scoliotic
      descriptors. The evolution of regional and local scoliotic descriptors was
      analyzed between two scoliotic visits on a cohort of 28 adolescents with
      progressive idiopathic scoliosis. Mean age at the first visit was 12.7 +/- 1.7
      years old and averaged time interval between two assessments reached 22.8 +/-
      10.8 months. Scoliotic descriptors were obtained from three-dimensionally
      reconstructed spines. The initial thoracic Cobb angle was on average 35.3 degrees
      +/- 8.4 degrees (range, 14 degrees-54 degrees). The evolution of spinal
      curvatures and vertebral deformities was assessed statistically in terms of
      descriptor absolute variations, and of descriptor variations normalized with
      respect to time and to the increase in Cobb angle. At the thoracic level,
      vertebral wedging increased with curve severity in a relatively consistent
      pattern for most scoliotic patients and axial rotation mainly increased towards
      curve convexity with scoliosis severity. No consistent evolution was associated
      with the angular orientation of the maximum wedging. Thoracic kyphosis changes
      (increase and decrease) were observed in important proportions. Results of this
      study challenge the existence of a typical scoliotic evolution pattern and
      suggest that the scoliotic evolution is quite variable and patient-specific.

PMID- 15457694
TI  - Adolescent idiopathic scoliosis: natural history and prognosis.
AB  - Retrospective review of the scoliosis database showed adolescent idiopathic
      scoliosis to be the most common but least significant variety of spinal
      deformity. Data from 112 girls diagnosed on repeat screening showed the
      importance of menarche as a date in the natural history. In the whole database,
      there were 514 aged at least 15 years at last review, 45 boys and 469 girls.
      Braces were prescribed for a total of 38, mostly during the early part of the
      period and gradually abandoned without an increase in surgical rate. Progression
      depended on the age and maturity of the patient as well as the initial Cobb
      angle. Surgery was recommended for 27% overall. A sub-group with more complete
      data diagnosed after bracing had been discontinued confirmed the findings.

PMID- 15457695
TI  - Prediction of spinal deformity in scoliosis from geometric torsion.
AB  - The shape of a curved line that passes through thoracic and lumbar vertebrae is
      often used to study spinal deformity with measurements in "auxiliary" planes that
      are not truly three-dimensional (3D). Here we propose a new index, the geometric
      torsion, which could uniquely describe the spinal deformity. In this study we
      assessed whether geometric torsion could be effectively used. to predict spinal
      deformity with the aid of multiple linear regression. Anatomical landmarks were
      obtained from multi-view radiographic reconstruction and used to generate 3D
      model of the spine and rib cage of 28 patients. Fourier series best fitted to the
      vertebral centroids approximated the spinal shape. For each patient, spinal
      deformity indices were computed. Torsion was calculated and 20 derived parameters
      were recorded. Torsion inputs were used in a multiple linear regression model for
      prediction of key spinal indices. The primary clinical Cobb angle (mainly
      thoracic) was predicted well, with r=0.89 using all 20 inputs of torsion or
      r=0.83 using just two. Torsion was also well related to the orientation of plane
      of maximal deformity (r=0.87). Torsion was less accurate but still significant in
      predicting maximal vertebral axial rotation (r=0.77). This preliminary study
      showed promising results for the use of geometric torsion as an alternative 3D
      index of spinal deformity.

PMID- 15457696
TI  - The natural history of early onset scoliosis.
AB  - A retrospective analysis of the natural history and treatment outcome of
      scoliosis, both idiopathic and syndromic, presenting before age 10 years was
      undertaken. The pattern was generally one of relentless progression, with little
      discernible benefit from orthotic treatment and surgical correction as the
      outcome for the majority. This result makes imperative a properly constructed
      study on the evolution and long-term outcome of this less common but more
      significant type of spinal deformity.

PMID- 15457697
TI  - The incidence of idiopathic scoliosis in Greece--analyais of domestic school
      screening programs.
AB  - INTRODUCTION: The aim of the study is the documentation of the national incidence
      of idiopathic scoliosis (IS) based on the School Screening programs performed at
      the various geographical departments of the country, and the estimation of the
      probable number of children who will need to be conservatively or surgically
      treated. MATERIAL-METHODS: During the years 1975 - 1999, 17 School Screening
      programs were performed in Greece and their results were analyzed and published
      in the book "School Screening in Greece". These studies had in common the
      children age distribution, the clinical examination, the radiological definition
      of IS when the Cobb - angle was > or = 5 degrees or > or = 10 degrees after SRS.
      The standing forward bending test was used. An Orthopaedic surgeon always
      participated in the scientific screening team. 215899 children aged 5.5 - 15
      years were screened. When there was suspicion of scoliosis, the child was further
      assessed radiolographically (standing postero - anterior spinal radiographs), for
      Cobb angle appraisal. RESULTS: In 130689 screened children, scoliosis was
      considered when the consequent radiological assessment revealed Cobb angle of >
      or = 10 degrees, (a), and in 85210 children when it revealed Cobb angle of > or =
      5 degrees respectively, (b). In (a) studies the scoliosis incidence was 2.9%
      (range 1.1 - 5.7%), and (b) 4.9% (range 2.7 - 9.5%) respectively. The right
      thoracic curves dominated in both (a) and (b) studies and thoraco - lumbar,
      lumbar and double curves followed. Among 7965 scoliotics out of the total sample
      of 215899 children, 4.5% were conservatively treated with the use of a brace, and
      only 0.19% was treated surgically. CONCLUSIONS: From data of 1998 national
      census, the population of children aged 8 to 14 years old was approximately
      751000. With the above -mentioned datum and with a national mean scoliosis
      incidence of 2.9%, (Cobb angle > or = 10 degrees), 21781 children will be found
      with scoliosis. 980 will need conservative treatment using a brace while 41
      children will need surgical treatment.

PMID- 15457698
TI  - School screening in the heavily industrialized area--Is there any role of
      industrial environmental factors in idiopathic scoliosis prevalence?
AB  - INTRODUCTION: School-screening programs contributed greatly to the study of
      idiopathic scoliosis (IS) prevalence. A similar program confined to a highly
      industrialized area is being performed in our Department. Thus the comparison of
      the findings of IS prevalence of this program with those of programs performed in
      non-industrialized areas of the same country could imply the significance of
      special industrial environmental factors on IS aetiology. MATERIALS AND METHODS:
      3039 schoolchildren (1506 boys, 1533 girls), aged 5,5 to 17,5 years, have been
      screened for IS. These children comprise 20% of a total population of 20000
      schoolchildren, who live in the region. The detection of the scoliotic children
      was attained utilizing the criterion of the angle of trunk inclination (ATI). The
      Prujis scoliometer was used to assess ATI. A cut off point of > or = 7 degrees
      ATI was used as a criterion for children's referral to hospital. 262 (8,6%) were
      referred for further evaluation, whereas 118 (3,9%) among these children
      underwent radiological examination. RESULTS: 90 children were found to have a
      Cobb angle of > or = 10 degrees at their standing PA spinal radiographs (2,9 % of
      the screened population). A Cobb angle of 10 degrees -20 degrees was found in 74
      (2,4%) children. Sixteen (0,5%) children, who had scoliotic curves with a Cobb
      angle of > or = 20 degrees, underwent conservative treatment by means of spinal
      orthosis. Relatively to their location on the vertebral column, 20% of the
      scoliotic curves were thoracic, 26,7% thoracolumbar, 20% lumbar, 24,4% double and
      8,9% miscellaneous. DISCUSSION: The screened area represents a place of
      particular interest because it experienced considerable environmental pollution
      during the past decades without any improvement of the available Health Services.
      A quite diverse population in relation to its occupation and its origin inhabits
      this area as well. The scoliosis incidence found in this area is similar to the
      incidence observed (2,9%) at other non-industrialized geographical departments of
      this country (2,6%). This implies that industrial environmental factors probably
      do not significantly influence the prevalence of AIS.

PMID- 15457699
TI  - Biomechanical factors affecting progression of structural scoliotic curves of the
      spine.
AB  - The development of the spine is affected by both biological and mechanical
      factors. As the geometry of the motion segment changes throughout growth, so does
      the mechanical behaviour of the spine owing to changing vectors acting on a
      variable geometry system. The biomechanical analysis of the growing spine enables
      the assessment of the role played by biological and mechanical factors in the
      pathogenesis of progressive scoliosis to be assessed and its comparison with
      factors acting on an adult scoliotic spine. The knowledge of these principles is
      instrumental to setting the right parameters for treatment and to design braces
      that may be capable of obtaining correction of the deformity. The elastic
      behaviour of child and adult spine differs because of both physiologic and
      pathologic conditions. In child scoliosis an abnormal geometry causes a
      persistent stress concentration in crucial areas of the motion segment. This
      induces a progressive elasto-plastic strain which modifies the geometry of the
      motion segment, thus worsening the stress concentration and the excessive strain
      through a vicious cycle. In adult scoliosis, on the other hand, deformation
      primarily affects the viscous-elastic structures, namely the intervertebral disc
      and the capsulo-ligamentous structures. This produces instabilty of the motion
      segments and slow deformation of the vertebrae through remodelling. It therefore
      ensues that the aim of the treatment differs in both conditions. In the child
      spine the aim is to prevent the motion segment deformity by means of braces which
      adequately modifies the stress distribution acting on the spine, thus enabling
      the spine to grow according to a quasi-physiological model. In adult scoliosis a
      stable equilibrium is required in order to prevent further deformation of the
      motion segment.

PMID- 15457700
TI  - Positional cloning strategies for idiopathic scoliosis.
AB  - AIM: Idiopathic scoliosis (IS) affects approximately 1-2% of the population and
      has a heritable component. It is clear that in general IS displays the features
      of a complex genetic disorder; however families displaying a Mendelian
      inheritance pattern have been described. Our aim is to identify families
      segregating rare, highly penetrant loci. In the case described here the disorder
      appears to cosegregate with a chromosomal rearrangement. METHODS AND MATERIALS:
      We have studied a family in which a pericentric inversion of chromosome 8 appears
      to cosegregate with idiopathic scoliosis in three generations. We have used
      fluorescent in situ hybridization (FISH) to identify cloned DNAs that span the
      breakpoints on the two arms of the chromosome. These clones allow the recovery of
      sequence information from the breakpoint region and identification of candidate
      genes. RESULTS: We have identified a YAC of 1190kb that spans the p arm
      breakpoint and from this a cosmid of 35kb that also identifies the break. We have
      derived DNA sequence information on this region. We have identified a BAC of
      150kb that crosses the q arm breakpoint. The complete genomic DNA sequence of
      this BAC is being analyzed to identify candidate genes and to further localize
      the precise breakpoint. CONCLUSION: We have sublocalized within two small genomic
      regions the position of a possible locus for idiopathic scoliosis.

PMID- 15457701
TI  - Prediction of curve progression in idiopathic scoliosis from gene polymorphic
      analysis.
AB  - Three hundred and four girls with adolescent idiopathic scoliosis were
      investigated to determine if DNA polymorphisms in the vitamin D receptor (VDR),
      estrogen receptor (BR), and CYP17 gene were related to curve progression of
      idiopathic scoliosis. The results suggested that XbaJ site polymorphism in the ER
      gene was associated with curve progression. The Cobb's curve angle with genotype
      XX and Xx was statistically greater than that with genotype xx. The curve
      progression risk (approximately 5 degrees) was higher for genotype XX and Xx than
      for genotype xx. Furthermore, patients with genotype XX and Xx had a higher risk
      of receiving operative treatment than those with genotype xx. In conclusion, DNA
      analysis may predict curve progression, although other polymorphisms were not
      associated with curve severity.

PMID- 15457702
TI  - Mechanical modulation of vertebral and tibial growth: diurnal versus full-time
      loading.
AB  - The aim of this study was to determine whether the amount of growth response to
      mechanical compression and the underlying mechanism differed with night-time or
      day-time loading, relative to full time loading. Mechanical compression
      (nominally 0.1 MPa stress) was applied across tibial and tail vertebral growth
      plates of growing Sprague-Dawley rats. Four groups of animals were tested: 24/24
      hour (full-time loading); 12/24 hour (day-loading); 12/24 hour (night-loading);
      and 0/24 hour (sham instrumented), 4 or 5 animals per group. After 8 days animals
      were euthanized and the growth plates were processed for quantitative histology
      of loaded and within-animal control growth plates to measure 24-hour growth,
      total and BrdU-positive proliferative zone chondrocyte counts, and hypertrophic
      chondrocyte enlargement in the growth direction. RESULTS: Growth as a percentage
      of within-animal control averaged 82% (full-time); 93% (day-loading); 90% (night
      loading); 100% (sham) for vertebrae. For proximal tibiae it averaged 70% (full
      time); 84% (day-loading); 86% (night-loading); 89% (sham). Reduced amount of
      hypertrophic chondrocytic enlargement explained about half of this effect in full
      time compressed growth plates, but was not significantly altered in half-time
      loaded growth plates. The remaining variation in growth was apparently explained
      by reduced total numbers of proliferative zone chondrocytes. The BrdU labeling
      index demonstrated an opposite trend, which was not statistically significant. In
      half-time loaded growth plates the proliferative zone cell count change
      predominated.

PMID- 15457703
TI  - Growth patterns in patients with unoperated congenital vertebral anomaly.
AB  - Retrospective analysis of height and weight data recorded during routine clinic
      visits of children with congenital vertebral anomaly were related to decimal age
      and compared with national centiles. Individuals were dropped from the study at
      surgery. Growth followed a normal trajectory until puberty, although girls tended
      to be smaller than average. At puberty, they lagged behind their peers and at
      maturity were shorter than average. This does not appear to be a hormonal
      problem, and suggests a fundamental failure of growth.

PMID- 15457704
TI  - Morphometric characteristics of the thoracic and lumbar pedicles in the Greek
      population.
AB  - OBJECTIVES: To measure the dimensions of the pedicles of T1 to L5 in the Greek
      population. METHODS: A total of 12 whole human cadaver spines were evaluated
      regarding pedicle dimensions (5 women and 7 men). The mean age at the time of
      death was 69,6 (range 62 to 84 years). The transverse and sagittal out side
      pedicle isthmus widths, the internal transverse diameter and cortex width were
      measured with electronic calipers both on the right and left pedicles. The data
      collected were statistically analyzed with the t-test. RESULTS: The widest
      transverse diameter was at the L5 level with a mean of 11,3mm (range 7,55
      15,46mm). The narrowest transverse diameter was at the T5 level with a mean of
      5,37mm (range 4,10-6,88mm). The widest sagittal diameter was at the T11 level
      with a mean of 17,23mm (range 14,84-19,57mm), while the narrowest one was at T1
      level with a mean of 9,1mm (range 7,18-11,37mm). The maximum internal transverse
      diameter was at the L4 level with a mean of 8,26 mm (range 7,10-9,23mm) while the
      minimum was at the T5 level with a mean of 3,9mm (range 3,14-4,78mm). The maximum
      cortex width was at the L5 level with a mean of 2,55mm (range 2,15-3,02mm) and
      the minimum at the T5 level with a mean of 1,30mm (range 0,40-2,10mm).
      CONCLUSIONS: From the statistic analysis of the above data it was found that
      regarding the internal diameter there was statistically significant difference
      between males and females especially at T3, T7, T8 and L3 levels (P<0,05), and
      almost in all levels regarding the cortex width. There was also statistically
      significant difference between right and left pedicles regarding the transverse
      and the sagittal widths (P<0,05). The narrowest pedicle was at the T5 level and
      the widest was at the L5.

PMID- 15457705
TI  - Does coralline hydroxyapatite conduct fusion in instrumented posterior spine
      fusion?
AB  - OBJECTIVES: This study was conducted to investigate the course of incorporation
      of coralline hydroxyapatite in human spine. SUMMARY OF BACKGROUND DATA:
      Conventional techniques for surgical treatment of spine have a substantial
      failure rate and associated morbidity. Bone graft substitutes are an alternative
      technique to enhance fusion rates and limit the morbidity associated with spine
      fusion using autologous iliac crest bone graft. There are some experimental
      studies supporting the use of hydroxyapatite in spine surgery. MATERIAL &
      METHODS: During revision surgery specimens derived from the fusion mass from 15
      operations in 13 patients, who received spinal instrumentation and fusion in
      cervical, thoracic, and lumbar spine and addition of coralline hydroxyapatite.
      The age of patients at the time of revision surgery was 46 +/- 20 years. The time
      lapsed from the implantation of coralline hydroxyapatite and revision surgery was
      11 +/- 9 months. The indication for revision surgery was infection,
      pseudarthrosis, technical error, and pain related to bulky hardware. The
      diagnosis for the primary fusion was degenerative disease, trauma and scoliosis,
      and the material of instrumentation used was composed from titanium alloy. The
      coralline hydroxyapatite was applied on the decorticated posterior elements of
      the instrumented spine. Material from ten different places from the fusion mass
      was intraoperatively taken in all patients and was sent for histological
      evaluation using the Hematoxylin-eosin histological stain technique and
      photomicroscope. RESULTS: Under photomicroscope there was a remarkable
      concentration of foreign-body like giant cells & development of inflammatory
      granulation tissue around hydroxyapatite, which was gradually replaced by dense
      connective collagen tissue. Both inflammatory granulation and collagen tissue
      showed areas with foreign body reaction. In the cases, where bone has developed,
      the most initial finding was the presence of osteoblasts & apposition of osteoid
      in contact to hydroxyapatite granules. In a later phase, cancellous and lamellar
      bone has developed as a result of secondary ossification. Bone formation was
      observed in 11/15 cases and was related with the patient's age in favor of young
      patients (R=0.56, P<0.05), while there was no correlation with time lapsed from
      operation. CONCLUSION: Coralline hydroxyapatite conducts bone formation in spine
      surgery because in the vast majority of the operated cases for different spinal
      disorders bone and osteoid has developed around the implanted coralline
      hydroxyapatite.

PMID- 15457706
TI  - The effects of mechanical loading on the mRNA expression of growth-plate cells.
AB  - Bone growth is a complex process involving proliferation, maturation and
      hypertrophy of chondrocytes in the growth plates. Mechanical forces applied to
      growing bones alter their longitudinal growth. However, the mechanisms by which
      chondrocytes modulate longitudinal bone growth are not well understood. This in
      vitro study investigated the effects of mechanical loading on the mRNA expression
      pattern of key molecular components of the growth-plate. Short-term static
      loading was applied to rat proximal tibial growth-plate explants. Various age
      groups at specific developmental stages were investigated. In situ hybridization
      was used to assess the mRNA expression of the cells in different zones of the
      growth-plate. Four key components were investigated: 18s (basic cell metabolism),
      type II collagen (major extracellular matrix component), type X collagen (matrix
      component in hypertrophic zone) and PTH-PTHrP receptors (pre-hypertrophic
      chondrocytes). The spatial variation in the mRNA expression between loaded
      explants and their contralateral controls was compared to establish: -the
      sensitivity of the different growth-plate zones to mechanical loading; -the
      sensitivity of the different developmental stages to loading. Preliminary results
      indicated that static loading on the growth plate of 80 d.o. rats affects type II
      and X collagen gene expressions while PTH-PTHrP remains insensitive to static
      loading. Improved understanding of growth-plate mechanics and the underlying
      biology is required to provide a scientific basis for the treatment of
      progressive deformities.

PMID- 15457707
TI  - Back shape assessment in each of three positions in preoperative patients with
      adolescent idiopathic scoliosis: evaluation of a 10-level Scoliometer method
      interpolated to 18-levels.
AB  - A Scoliometer was used by one observer (RKP) to assess the reproducibility of
      angle of trunk inclinations (ATIs) in 13 preoperative patients with AIS (thoracic
      7, thoracolumbar 6, mean Cobb angle 50 degrees, right 9, age 15.4 years, girls
      10). Three positions were used namely standing forward-bending, (FB) sitting FB
      and prone. Readings of ATI on the back were obtained at each of 10 levels (T1
      S1). The subject was repositioned after walking around the room and a second set
      of readings obtained (repeats). All readings were converted by a computer program
      to 18 levels and plotted. The readings from 18 levels were analysed by level, as
      well as summated and averaged both without and with correction for the side of
      the curve. Conclusions. Back surface asymmetry measured with a Scoliometer in
      these preoperative patients with AIS is less in the prone position than in each
      of the forward bending positions. The standing FB position has the best
      reproducibility which supports the practice of using this position to measure
      Scoliometer ATIs in preoperative patients with AIS.

PMID- 15457708
TI  - New approach to objective diagnostics of polyfunctional disorders of the
      neuromuscular regulation in children with various forms of spine deformities.
AB  - A combination of two methodical approaches (parallel evaluation of the
      psychomotor function and metabolic shifts) was used in examination of children
      with scoliosis. We evaluated adaptation of children at the certain stage of the
      disease for prediction of its further course and correction of the treatment.

PMID- 15457709
TI  - Spinal mobility and EMG activity in idiopathic scoliosis through dynamic lateral
      bending tests.
AB  - Lateral bending test is a common evaluation of AIS patients prior to their
      surgical correction. Traditionally this evaluation is made by the assessment of
      the curve's flexibility from side-bending radiographs. As a complement to this
      static test, dynamic bending was experimented while simultaneously quantifying
      muscular and kinematic behavior of the spine. The biggest contribution to total
      EMG output was 36% from lumbar muscles in healthy and 35% from abdominal muscles
      in scoliotic subjects. Continuous measuring of kinematics and muscle activation
      patterns throughout lateral bending could be an evaluation tool for
      distinguishing pathological from normal behavior.

PMID- 15457710
TI  - Three dimensional analysis of chest wall motion during breathing in healthy
      individuals and patients with scoliosis using an ultrasonography-based system.
AB  - The mechanical inefficiency during respiration in scoliosis remains unclear. AIM:
      To study the three-dimensional motion of the chest wall during deep breathing in
      healthy and scoliotic individuals. MATERIALS & METHODS: Three-dimensional chest
      wall motion during breathing was studied in 17 scoliotic patients (right thoracic
      curvature) and 9 healthy individuals. Measurements were performed using a Zebris
      CMS 70P system (Zebris Medizintechnik Gmbll, Isny, Germany) which analyzes the
      time delay of ultrasound pulses emitted from markers placed on the chest wall.
      Nine markers were attached on the upper, the middle and the lower chest wall.
      Subjects were seated on a chair and asked to breathe deeply and slowly with no
      elevation of the shoulders for one minute. RESULTS: The amplitudes were symmetric
      between the two sides in healthy individuals while scoliotic patients exhibited
      asymmetric chest wall motion. The amplitudes of the right convex side of the
      chest wall exhibited less motion than those of the left concave side, especially
      on the lower chest wall. CONCLUSION: Chest wall motion was asymmetric in the
      scoliotic patients with diminished motion of the right lower chest wall. This
      locally diminished ventilation may cause ventilation-perfusion inequality and
      result in hypoxemia.

PMID- 15457711
TI  - Relation between the pelvis and the sagittal profile in adolescent idiopathic
      scoliosis: the influence of curve type.
AB  - Previous studies have shown a correlation between pelvic parameters and the
      lumbar lordosis in normal subjects and in scoliotic adults. This study
      investigates the relationship between pelvic and spinal geometries in the
      sagittal plane for adolescent idiopathic scoliosis (AIS) patients having various
      curve types. The study group was composed of 129 AIS patients classified
      according to their curve type: King I, King II, King III or lumbar curve. The
      SpineView software (Surgiview, France) was used to compute five parameters on
      sagittal x-rays: thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS),
      pelvic tilt (PT) and pelvic incidence (PI). The TK was significantly lower for
      King I, II and III curves as compared to the lumbar curves. The LL tended to be
      higher for patients having a major lumbar scoliotic (King I and lumbar) curve,
      although not significantly. No significant change between the groups was observed
      for the SS, PT and PI. The PI was significantly correlated to the LL, SS and PT
      for all groups. The SS was strongly related to the LL in all cases. However, no
      relationship was found between the TK and the LL in any group. This study showed
      that the TK mostly depends on the thoracic scoliotic curve and therefore on the
      shape and orientation of the vertebrae, which explains that many King I, II and
      III patients are hypokyphotic. Conversely, the LL is mainly influenced by the
      pelvic configuration. Since the pelvic parameters are similar for all groups,
      these parameters are not likely to be important in the development of a specific
      type of scoliotic curve.

PMID- 15457712
TI  - Study of patient positioning on a dynamic frame for scoliosis surgery.
AB  - The goal of this clinical trial was to measure patient geometry on a dynamic
      positioning frame in various prone positions. Fourteen subjects (2 males and 12
      females) were recruited from the scoliosis clinic at Ste-Justine Hospital on a
      volunteer basis. The subjects were AIS patients who were potential candidates for
      surgery. The Cobb angle, averaged 50 degrees (32 degrees-64 degrees). The mean
      age was 14.1 years (11-17). A Polaris system (Northern Digital inc, Canada) with
      10 passive reflective markers was used to measure various indices of the
      patient's trunk geometry. Acquisitions were made while the unanaesthetized
      patient was in five different prone positions: I similar to the standard
      positioning on a Relton-Hall frame; II addition of a force applied to the ribcage
      at the apex of the curve; III application of a force at the apex of the curve in
      the lumbar region; IV, the shoulder pads were elevated to increase the patient's
      kyphosis; V adjustment of each pad and the application of thoracic and lumbar
      forces to obtain an optimal correction. The measurements of trunk geometry at
      each position were compared using position I as a base. A paired student t-test
      determined a significant difference between positions. When comparing position I
      to position II there was a significant difference and correction of the rib hump.
      There was also a significant change in shoulder angle that resulted in over
      correction. Position III had a significantly negative change in the rib hump.
      During position IV, there was a measurable increase in kyphosis. During the
      optimal correction, position V, a significant increase in spine length was
      observed as well as a significant correction in rib hump and shoulder angle.
      Patient trunk geometry can be improved by the application of different forces on
      a dynamic positioning frame. Caution is necessary as over correction and
      unintended negative effects were observed. The optimal patient position has not
      yet been found and future studies are directed at determining this.

PMID- 15457713
TI  - Joint segmental kinematic trunk motion and C.O.P. patterns for multifactorial
      posturographic analysis.
AB  - Measurements of postural sway are used to determine a subject ability to maintain
      upright stance. In many clinical analyses, postural control measured during a
      quiet standing provides very useful insights about CNS and Motor control
      behaviour. The aim of this paper is to present a new posturographic methodology
      including both classical parameter extraction techniques and new specially
      developed figuring algorithms, in which both kinematic patterns and ground
      reaction force COP evolution are jointly processed in order to identify the
      biomechanical behaviour in particular of the spine at each metameric level for
      both orthostatic posture and lateral bending test.

PMID- 15457715
TI  - Baropodographic measurements and averaging in locomotion and postural analysis.
AB  - The use of quantitative baropodography measurements, either by means of pressure
      sensing foot insoles or floor mats, is quickly increasing in clinical and
      research fields for the analysis of a wide variety of foot and ankle disorders.
      In this paper we present a set of complex and detailed processing procedures
      necessary to correctly perform gait cycles normalisation and averaging as well as
      bivariate statistic for COP analysis, in order to extract quantitative and
      statistically significant parameters for clinical evaluation of locomotion and
      orthostatic posture.

PMID- 15457714
TI  - Transverse plane pelvic rotation measurement.
AB  - AIM: To determine how pelvic rotation in the transverse plane relates to coronal
      plane anatomical landmark location. The problem this addresses is the observation
      that iliac crest medial lateral width as seen in the coronal plane Cobb is often
      asymmetrical in patients with idiopathic scoliosis before treatment, and
      sometimes after treatment. MATERIALS AND METHODS: A pelvis was marked with
      radiographically opaque markers at symmetrical sites in the ilium, sacrum and
      acetabulum; mounted in a jig; and radiographed at varying degrees of transverse
      and sagittal plane angulation. The medial lateral distance from two similar
      landmarks on opposite sides of the pelvis was then determined and a left/right
      ratio correlated with the degrees of transverse plane angulation. In addition, a
      theoretically derived equation was developed to describe the effect of pelvic
      shape on the degree of transverse plane rotation. RESULTS: The left/right ratio
      for the distance from the sacro iliac joint to the anterior superior iliac spine
      proved to be the most reliable for determining the degree of pelvic rotation in
      the transverse plane. The relationship is nearly linear up to 25 rotation and is
      little influenced by the degree of sagittal plane angulation. Based on
      theoretical considerations, the importance of the anterior to posterior angular
      relationship of the two coronal plane landmarks measured influences the degree of
      rotation but not the linear relationship. CONCLUSION: Within limits the
      transverse plane rotation of the pelvis can be determined by a left/right ratio
      of the distances between two similar landmarks on each side of the pelvis.

PMID- 15457716
TI  - Movement analysis of scoliotic subjects using Fastrak.
AB  - An attempt has been made to simplify the measurement of composite movement
      involving abnormal rotation in scoliosis, which is considered to have an
      important role in the diagnosis and treatment of the condition. Analysis of three
      dimensional movement provides pertinent information concerning the morphological
      description of scoliotic deformities. The description of this movement is of
      clinical interest for aiding diagnosis and/or prognosis of spinal deformity
      evolution. Previous studies have indicated that idiopathic scoliosis is a three
      dimensional deformity accompanied by a generalised torsion phenomenon and
      attempts have been made to associate the geometric torsion index with the curvi
      linear shape of idiopathic scoliosis. Although previous investigations have
      documented the three-dimensional reconstruction of scoliotic spine, most methods
      either expose the subject to a high level of radiation, as in stereo-radiographs,
      or demand a high degree of technical input and time, as in video based gait
      analysis systems. This study employs an electro magnetic field capturing system
      (FASTRAK) to estimate the spinal movements. This simple system is inexpensive and
      highly portable. Furthermore, it can give instant graphic and numerical values of
      the composite movement. The results of this study indicate the usefulness this
      system in the diagnosis of scoliosis and highlights the possibility of its uses
      in screening school children and other surveys.

PMID- 15457717
TI  - Motion segment stiffness measured without physiological levels of axial
      compressive preload underestimates the in vivo values in all six degrees of
      freedom.
AB  - Axial preload is known to alter the mechanical properties of spinal motion
      segments. The objective of this study was to compare the experimentally measured
      load-displacement behavior (stiffness, hysteresis and linearity) of porcine
      lumbar motion segments in vitro with physiological axial compressive preloads of
      0, 200 and 400 N equilibrated in a physiological fluid environment. At each
      preload, displacements in each of six degrees of freedom (+/- 0.3 mm AP and
      lateral translations, +/- 0.2 mm axial translation, +/- 1 degrees lateral bending
      and +/- 0.8 degrees flexion/extension and torsional rotations) were imposed. The
      resulting forces and moments were recorded. Tests were repeated after removal of
      posterior elements. Using least squares, the forces at the vertebral body center
      were related to the displacements by a symmetric 6x6 stiffness matrix. The
      stiffness, hysteresis area and linearity of six diagonal and two off-diagonal
      load-displacement relationships were examined for differences between preload
      conditions. RESULTS: Mean values of the diagonal terms of the stiffness matrix
      for intact porcine motion segments increased significantly by an average factor
      of 2.2 and 2.9 with 200 and 400 N axial compression respectively (p<0.001).
      Increases for isolated disc specimens averaged 4.6 and 6.9 times with 200 and 400
      N preload (p<0.001). Changes in hysteresis correlated with the changes in
      stiffness. The load-displacement relationships were progressively more linear
      with increasing preload (R2 = 0.82, 0.97 and 0.98 at 0, 200 and 400 N axial
      compression respectively). Motion segment and disc load-displacement behaviors
      were stiffer, more linear and had greater hysteresis with axial compressive
      preloads.

PMID- 15457718
TI  - Kinematic differences in lower limb gait analysis of scoliotic subjects.
AB  - Although various factors have been attributed to the etiology of idiopathic
      scoliosis, studies have indicated that the kinematic differences in the spine,
      pelvis and lower limb may contribute to the causation and progression of
      idiopathic scoliosis. The aim of this investigation was to identify asymmetries
      in lower limb kinematics and pelvic and back movements during level walking in
      scoliotic subjects that can be related to the spinal deformity. The study has
      employed a movement analysis system to estimate various joint angles in the lower
      extremities and other kinematic parameters in the pelvis and back. The results of
      a pilot study have highlighted the potential usefulness of a range of parameters
      in the indication of asymmetries and their implications for spinal deformity
      generation. While demonstrating the value that movement analysis systems may have
      in investigating pathogenesis and aetiology, these preliminary findings indicate
      that the identified variables can also used in the kinematic analysis of spinal
      deformities such as scoliosis. Further studies are being undertaken to validate
      these findings.

PMID- 15457719
TI  - Assessing changes in three dimensional scoliotic deformities with difference
      maps.
AB  - Topographical difference maps were used to compare the trunk surfaces of subjects
      over the course of their treatment. Three-dimensional points representing the
      trunk surfaces were aligned accounting for growth and positioning. A goodness-of
      fit score was calculated and a color map used to display trunk surface changes.
      Fifty-one successive subjects were assessed with difference maps. Two subjects
      each had 10 repetitions taken on the same day to assess reliability. A blinded
      observer used a five-point scale that extended from full agreement to full
      disagrment to judge the maps according to the extent and location of changes. The
      observations were compared to clinical measures mapped onto the same scale by
      another blinded observer. Goodness of fit for repeated measures averaged 5 +/- 1,
      for subjects deemed to have no change 7 +/- 2, for subjects with slight change 9
      +/- 2, and 14 +/- 2 for subjects with significant change. Judges were in full
      agreement or in agreemnt with forty of the fifty-one subjects (78%) and in slight
      disagreement with the remaining eleven. When the cohort was subdivided in
      surgical, brace and no treatment groups, the judges were in full agreement or in
      agreement 76%, 80%, and 85% respectively. The difference map provides a
      qualitative and quantitative measure of how the trunk surface has changed as a
      whole.

PMID- 15457720
TI  - Three-dimensional shape analysis of the scoliotic spine using MR tomography and
      rasterstereography.
AB  - Rasterstereography delivers only indirect information about the three-dimensional
      shape of the spine. Therefore, validation with radiologic methods is necessary,
      in particular in severe scolioses above 50 AE Cobb. Comparison with conventional
      a.p. radiographs yielded satisfactory results for scolioses up to 50 AE Cobb, but
      only in frontal view, i.e. in two dimensions. A true three-dimensional validation
      is possible only with MR tomography, however this is difficult due to severe
      technical limitations. In the present study 26 patients with Cobb angles between
      26 AE and 116 AE were examined both with MR tomography and rasterstereography.
      Comparing the shape of the spinal midline as measured by the two methods we found
      that a) the gross 3-d shape of the spinal midline is well reproduced by the
      rasterstereographic model, b) the lateral rms error is about twice as large as
      with conventional radiographs and c) that the rms errors increase with increasing
      Cobb angle. This means that the rasterstereographic model reconstruction must be
      modified for severe scolioses.

PMID- 15457721
TI  - The effect of posture on Quantec measurements.
AB  - The effect of moving the patient's centre of gravity from one extreme to the
      other, where the weight is entirely supported on the left or right foot at either
      extreme, was investigated in 33 patients attending for surface topography
      measurements with the Quantec Spinal Measurement System. Average changes of about
      20 were seen in the measured curvature of the lower spine line and pelvic tilt,
      but there was considerable variation between individual patients. When such
      extremes of stance were included, the reproducibility of measurements of the
      curvature of the lower spine, pelvic tilt and vertical alignment was poorer, but
      not to the extent that a significant improvement in reproducibility would be
      expected if the patient's centre of gravity was closely controlled with, for
      example, a force platform.

PMID- 15457722
TI  - Local energy as a measure of back symmetry in scoliosis.
AB  - The Cobb angle has been the most commonly used method in measuring the severity
      of scoliosis and its progression. However, in recent years a number of
      researchers have chosen to monitor scoliosis by examining the severity of the
      surface deformity resulting from the scoliosis. Each of these approaches has been
      limited by errors introduced in manual location of landmarks. Scoliosis results
      in an asymmetry of the back. It would be very desirable to have a computer-based
      method of measuring this asymmetry. This paper investigates the use of wavelets
      and the concept of local energy to measure asymmetry associated with scoliosis.
      The local energy model uses wavelet theory to obtain information about shading
      and boundaries of objects in an image. Edges and sharp discontinuities are areas
      of high local energy in an image. Features such as scapular prominence, shoulder
      edges, waist creases and other anomalies that contribute to the scoliotic back
      asymmetry have high local energy. A preliminary study was completed to determine
      if this approach was applicable to measurement of back asymmetry. Two-dimensional
      local energy images were created from photographs of the backs of patients with
      scoliosis. The local energy was integrated across each image and a left-to right
      line of symmetry was calculated. This line of symmetry was then correlated with
      the scoliotic score developed by our group. This technique shows promise of
      providing an automatic method of measuring scoliosis progression.

PMID- 15457723
TI  - Monitoring the thoracic sagittal curvature in kyphoscoliosis with surface
      topography: a trend analysis of 57 patients.
AB  - Records of Quantec measurements of tlie kypliotic curvature of the back were
      reviewed for all patients attending the children's orthopaedic clinic who were
      referred for back shape measurements. Of these, 57 children had five or more
      preoperative visits allowing trends to be calculated. Linear trends were found in
      30 of the patients, with gradients ranging from 1.1 degree/yr to 7.2(0)1/yr. On
      average, the scatter of measurements about the trend line, or about the mean
      value in the other 27 cases, compared well with that expected from repeatability
      studies but the amount of scatter varied from one patient to another. This may
      well be due to sampling. Where such measurements are monitored for evidence of
      change in an individual patient, the possibility of larger than average scatter
      about any emerging trend should be considered.

PMID- 15457724
TI  - Use of functional tests to increase the efficiency of scoliosis screening
      diagnosis by COMOT method.
AB  - COMOT technique was developed at Novosibirsk Research Institute of Traumatology
      and Orthopaedics as a pilot study in 1997 was used for screening for spine
      deformities in schoolchildren in Novosibirsk, Omsk and Moscow. Topographic
      screening was performed with patient standing in his natural free and easy
      posture. The criteria for scoliosis detection was an angle of lateral asymmetry
      (LA), calculated on the basis of topographic data, which was an analogue of Cobb
      angle. An additional criterion for structural spine deformation was an angle of
      scoliotic arch apex rotation (R). The analysis of responsiveness and specificity
      of topographic test (TT) at detection of structural arches of 10 and more degrees
      (according to Cobb) showed that they depend on the level of taken thresholds.

PMID- 15457725
TI  - Cotrel-Dubousset instrumentation (CDI) in the treatment of congenital spinal
      deformities. Computer topography evalution.
AB  - AIM OF THE STUDY: CDI and other types of segmental instrumentation are wide used
      in surgical treatment of congenital spinal deformities. At the same time we
      didn't find in orthopaedic literature any data concerning 3-D evaluation of the
      results of such procedures. The aim of this study is the assessment of 3-D effect
      of CDI using of computer optical topography.

PMID- 15457726
TI  - Three-dimensional correction with CD instrumentation and Harrington rod in the
      treatment of idiopathic scoliosis.

PMID- 15457727
TI  - Motion analysis of the trunk and spine. Surface measurement using computer
      optical topography.

PMID- 15457728
TI  - Development of the neurocentral junction as seen on magnetic resonance images.
AB  - The neurocentral junction (NCJ) is a cartilaginous growth plate in the vertebra
      that has been implicated as a potential cause of adolescent idiopathic scoliosis
      (AIS) since the early 1900s. Studies to date have focused on the age of closure
      without characterizing normal NCJ development. Using MRI, the normal development
      of the NCJ image can be determined and the stages preceding the disappearance of
      the NCJ image can be characterized. 405 NCJs from 11 pediatric patients were
      examined using MRI and the various images were categorized. NCJ development
      encompassed five stages, with a specific pattern of absence of the NCJ image
      noted in each vertebra and in the vertebral column as a whole. The image of the
      NCJ first became absent in the cervical region (age 6), then in the lumbar region
      (age 12) and finally in the thoracic region (age 14). These patterns of
      development serve as a baseline to evaluate NCJ pathology in conditions such as
      adolescent idiopathic scoliosis (AIS).

PMID- 15457730
TI  - Accuracy of rasterstereography versus radiography in idiopathic scoliosis after
      anterior correction and fusion.
AB  - Rasterstereography enables to reduce the number of radiographs in the
      conservative treatment of idiopathic scoliosis (Cobb angles below 50 degrees).
      The aim of the present study was to evaluate the use of rasterstereography in
      severe scoliosis before and after anterior surgery. The results show that the
      accuracy (as compared to radiographs) is lower in the pre-operative
      rasterstereographs. However, after operation the Cobb angles were less than 50
      degrees in all cases and the accuracy of the rasterstereographs was similar to
      that of non-operated scolioses. This finding might allow a significant reduction
      of post-operative radiographs.

PMID- 15457729
TI  - The components of the magnetic resonance image of the neurocentral junction.
AB  - The neurocentral junction (NCJ) is a cartilaginous growth plate located between
      the vertebral centrurn and the neural arch. In characterizing the age of closure
      of this growth plate, anatomic studies have suggested that the NCJ closes before
      age 10, whereas MRI studies have suggested that the NCJ does not fuse until
      adolescence In this study, gross anatomic and histologic sections were correlated
      with MR images to determine the components of the NCJ image. The NCJ image
      appeared as a thick white line that was shown to encompass the cartilage of the
      growth plate, the surrounding woven bone and a portion of the trabecular bone of
      the vertebra. Although the MR pixels were too large to completely resolve the
      tissues that surround the growth plate, MRI was shown to be a valuable technique
      of visualizing the NCJ cartilage and further MRI studies of the human NCJ are
      needed.

PMID- 15457731
TI  - Spine-rib rotation differences at the apex in preoperative patients with
      adolescent idiopathic scoliosis: evaluation of a three-level ultrasound method.
AB  - This paper evaluates a new real-time ultrasound method to assess the difference
      between axial spinal (laminal) rotation and rib rotation at the apex of the
      scoliosis curve. An Aloka SSD 500 portable ultrasound machine with a veterinary
      long (172mm) 3.5 MHz linear array transducer was used to assess the
      reproducibility of the method in 13 preoperative patients with AIS. With the
      subject in a prone position and her head supported, readings of laminal and rib
      rotation were made directly on the back at 18 and 12 levels respectively The
      subject was repositioned after walking around the room and a second set of spinal
      and rib rotations obtained (repeats). All the readings were made by one observer
      (ASK). After plotting on graphs three levels of maximal difference between spine
      rotation and rib rotation about the apex were chosen visually by one observer
      (RGB) for which the mean apical spine-minus-rib rotation difference (SRRD) was
      calculated for each repeat. Findings for apical SRRDs. The mean apical SRRDs for
      the two repeats are 7.1 degrees and 6.9 degrees (range 2-18 degrees) with
      coefficients of variation of 49% and 62% respectively. Reproducibility. Graphic
      representation of spinal and rib rotation by 12 levels shows a fairly good
      agreement between repeats for most subjects. Spinal rotation is always greater
      than rib rotation. A paired t-test for the mean apical SRRD of the repeats shows
      no significant difference. Linear regression analysis of the mean apical SRRD
      repeats correlate significantly (r=0.70, P=0.008) with a residual mean square of
      6.9 degrees (rms = 2.6 degrees). The technical error of the measurement (TEM) is
      2.3 degrees and coefficient of reliability (R) 0.66. Conclusions. Real-time
      ultrasound can assess the difference between spinal and rib rotation about the
      apex of the scoliosis curve without the altered position detectably affecting the
      findings. The error (2-3 degrees) is high relative the mean apical SRRD (6-7
      degrees). The apical SRRD findings have relevance to the pathogenesis of AIS.

PMID- 15457732
TI  - Sagittal and transversal plane deformity in thoracic scoliosis.
AB  - The aim of the study was to assess the sagittal and transversal plane deformity
      of the spine in thoracic scoliosis by the mean of 3-D radiographic analysis. 46
      patients admitted for surgery for thoracic idiopathic scoliosis underwent
      preoperative radiographic assessment. All patients presented the same pattern of
      the coronal plane deformity: single right thoracic curve (Lenke 1, King 3).
      Neither lumbar nor proximal thoracic structural curve were present. The Cobb
      angle varied from 41gamma to 77 gamma (mean 55,4 gamma +/- 8,6 gamma). Long
      cassette standing antero-posterior and lateral radiographs were analysed. Three
      dimensional reconstruction with Rachis 91TM software was performed for each pair
      of radiographs. The following parameters were assessed: sagittal thoracic Cobb
      angle (Th4-Th12), upper thoracic kyphosis angle (Th5-Th8), lower thoracic
      kyphosis angle (Th9-Th12), superior and inferior hemi-curve sagittal angles,
      lumbar lordosis, sacral slope, sacral incidence, vertebral plate index, segmental
      vertebral axial rotation throughout the thoracic and lumbar spine. Results showed
      great variability of parameters assessed. The non-harmonious distribution of
      kyphosis was demonstrated in the thoracic spine. Local Th9-Th12 hypokyphosis and
      adjacent local Th5-Th8 hyperkyphosis constitute the most typical sagittal
      pathologies. So called normokyphotic curves were composed of one hyperkyphotic
      and one hypokyphotic zone. Th1-Th4 segment revealed two patterns of segmental
      rotation distribution: a purely compensatory curve with no vertebral axial
      rotation or a rotated curve presenting the morphology intermediate between Lenke
      1 and Lenke 2 types (or King 3 and King 5). IN CONCLUSION: curves presenting the
      same coronal plane deformity differ in their morphology assessed in the two other
      planes; global thoracic kyphosis angle is a misleading parameter because it
      covers hypo- and hyperkyphotic zones; local distal thoracic (Th9-Th12)
      hypokyphosis is present in idiopathic thoracic scoliosis.

PMID- 15457733
TI  - A new X-ray calibration/reconstruction system for 3D clinical assessment of
      spinal deformities.
AB  - The main objective of this study was to develop a 3D X-ray reconstruction system
      of the spine and rib cage for an accurate clinical assessment of spinal
      deformities. The proposed system uses an explicit calibration technique and a new
      calibration object composed of: (1) a set of radiopaque markers embedded in a
      jacket worn by the patient during the X-ray exposures; (2) six control markers to
      define a reference vertical plane. Computer simulations were performed to
      evaluate the accuracy of the 3D reconstruction procedure when different kind of
      displacements were applied on a reference model. Clinical indices computed from
      the 3D X-ray reconstruction of the spine for 24 scoliotic subjects were compared
      to those obtained with the DLT method. The results of the evaluation study showed
      that the new system allows the patient to adopt a normal attitude without any
      constraint, compensating for its displacement between exposures.

PMID- 15457734
TI  - Preliminary study of a new real-time ultrasound method for measuring spinal and
      rib rotation in preoperative patients with adolescent idiopathic scoliosis.
AB  - A portable ultrasound machine with a linear array transducer was used by one
      observer (ASK) to evaluate the reproducibility for each of spinal (laminal)
      rotation and rib rotation in 13 preoperative patients with AIS (thoracic 7,
      thoracolumbar 6, mean Cobb angle 50 degrees, right 9, left 4, age 15.4 years,
      girls 10). With the subject in a prone position and her head supported, readings
      of spinal (laminal) and rib rotations were made directly on the back at 18 and 12
      levels respectively. The subject was repositioned after walking around the room
      and a second set of spinal and rib rotations obtained (repeats). Conclusious.
      Repositioning the patient significantly alters some single level readings of lam
      inal rotation and rib rotation. Although the mean average spinal rotation and rib
      rotation each have acceptable reproducibility, repositioning the patient
      significantly alters the findings. In the appraisal of surgery by ultrasound the
      positional change reported here for (I) single level laminal rotation and rib
      rotation, and (2) mean average rotation imposes caution on the interpretation of
      the findings. The method enables the axial spine-nh rotation differences to be
      evaluated which is the subject of a separate paper.

PMID- 15457735
TI  - Geometric and postural analysis of mild idiopathic scoliotic patients.
AB  - Understanding the aggravation process of mild idiopathic scoliosis is still a
      challenge. The aim of this study is to investigate the spine and pelvis
      configuration with regard to gravity line using 3D reconstruction coupled with
      foot pressure measurements. The distance between each vertebral center and the
      gravity line is calculated in order to observe the global equilibrium of spine. A
      protocol has been set and used for 10 mild idiopathic scoliotic patients. 34
      asymptomatic volunteers who were previously observed with the same protocol were
      used as reference for biomechanical comparisons. The first results showed
      differences between scoliotic and asymptomatic subjects and also among scoliotic
      patients. The proposed protocol should allow clinicians to follow up scoliotic
      patients with an innovative and efficient tool.

PMID- 15457736
TI  - Self-calibration of biplanar radiographs for a retrospective comparative study of
      the 3D correction of adolescent idiopathic scoliosis.
AB  - A novel technique for the 3D reconstruction of the spine from X-ray images is
      presented. The algorithm is based on the self-calibration of biplanar
      radiographs. It allows the 3D reconstruction of spines from old uncalibrated
      preoperative and postoperative radiographs. The reliability of the new self
      calibration technique was investigated by validating its results against those of
      the Direct Linear Transform (DLT) on real images. An accuracy experiment was also
      performed using a dry spine specimen under controlled conditions. The results
      indicate that self-calibration is a viable technique, accurate enough to extract
      meaningful 3D clinical data for retrospective studies.

PMID- 15457737
TI  - Semi-automation of the 3D reconstruction of the spine using wavelets and splines.
AB  - We propose a wavelet multi-resolution analysis to localize specific features in
      both lateral and frontal radiographs. This analysis allows an elegant spectral
      investigation that leads simultaneously to image de-noising and edge extraction.
      It is combined with an a priori knowledge of the spine's morphology and a 3D
      spline curve characterization of its global shape. Actual work deals with
      identifying the contours of the vertebral bodies and the localization of
      vertebrae's endplates. However, this information could also lead to the selection
      of a 3D statistical model of the spine suited for the studied deformation.
      Working with retro-projections of the model, we aim at creating edge models for
      each vertebra that will be used to geometrically match the wavelet's edges. The
      manual feature identification could then be replaced in the reconstruction of the
      3D representation of the spine.

PMID- 15457738
TI  - 3D biplanar statistical reconstruction of scoliotic vertebrae.
AB  - A new 3D reconstruction method of scoliotic vertebrae of a spine, using two
      calibrated conventional radiographic images (postero-anterior and lateral), and a
      global prior knowledge on the geometrical structure of each vertebra is
      presented. This geometrical knowledge is efficiently captured by a statistical
      deformable template integrating a set of admissible deformations, expressed by
      the first modes of variation in the Karhunen-Loeve expansion of the pathological
      deformations observed on a representative scoliotic vertebra population. The
      proposed reconstruction method consists in fitting the projections of this
      deformable template with the preliminary segmented contours of the corresponding
      vertebra on the two radiographic views. The 3D reconstruction problem is stated
      as the minimization of a cost function for each vertebra and solved with a
      gradient descent technique. The reconstruction of the spine is then made vertebra
      by vertebra. The proposed method allows also to efficiently obtain an accurate 3D
      reconstruction of each scoliotic vertebra and, consequently, it allows also to
      get an accurate knowledge of the 3D structure of the whole scoliotic spine. This
      reconstruction method is in final phase of validation.

PMID- 15457739
TI  - 3D detailed reconstruction of vertebrae with low dose digital stereoradiography.
AB  - As scoliosis requires a global and local 3D examination of the spine in standing
      position, stereoradiography appears as one of the most adequate 3D imaging tool
      for it diagnosis. Our purpose was to increase the geometry definition of the
      stereoradiographic reconstruction to obtain morpho-realistic models and to
      validate them using 41 dry vertebrae. Our results propose 2000 points 3D
      personalised models without any loss of accuracy in comparison to previous
      studies.

PMID- 15457740
TI  - Pre and post 3D modeling of scoliotic patients operated with in situ contouring
      technique.
AB  - A three-dimensional segmental analysis was performed on the stereoradiographic
      reconstructions of ten right thoracic scoliotic patients. From the quantitative
      model of the spine and pelvis, the vertebral and intervertebral orientations were
      computed pre and post operatively. These orientations allow to determine the
      apical and junctional zones of the high thoracic, thoracic and lumbar curves. The
      apical zone corresponds to the maximum of vertebral axial rotation. Pre
      operatively, the tendency was T7 for the thoracic transverse apex with 20 AE of
      axial rotation. The junctional zone corresponds to the maximum of vertebral
      lateral rotation and the maximum of intervertebral axial rotation. The tendency
      was T5 and T12 for the junctional vertebrae of the thoracic curve with, at both
      levels, 30 AE of vertebral lateral rotation and 10 AE of intervertebral axial
      rotation. The surgical correction obtained by in situ contouring technique was
      evaluated through these 3D orientations. The vertebral axial rotation at the high
      thoracic, thoracic and lumbar apex was corrected with respectively 52%, 60% and
      60%.

PMID- 15457741
TI  - 3D reconstruction and analysis of the whole trunk surface for non-invasive follow
      up of scoliotic deformities.
AB  - The purpose of this study was to evaluate the 3D reconstruction accuracy of a new
      technology that allows the acquisition of the whole trunk and to develop a
      software to analyse the trunk surface asymmetry. A non-invasive active vision
      system provides a 3D textured reconstruction of the whole trunk. The analysis
      system provides the clinician with quantitative indices that characterize the
      whole external trunk asymmetry.

PMID- 15457742
TI  - Assessment of the validity of observing three-dimensional images of the spine
      using polarising, synchronised techniques.
AB  - Three-dimensional imaging is an emerging technique in radiology. It might be used
      to help view the spine and assist in improving evaluation of scoliosis. These
      images are currently computer generated and although very effective are actually
      optical iflusions. Questions remain as to the reliability and validity of these
      images which are important considerations when treatment regimens are being
      developed and surgery contemplated. Using a constructed three-diemnsional image
      of a box, this study assessed the inter- and intra-reliability of viewing a
      specific point on this box and also the inter-reliability of identifying the
      coordinates of this same point. There was good reliability for viewing a single
      point in the X and Z axes which formed the plane of the computer but there was a
      10X decrease in reliability along the Y-axis (depth). This pattern was repeated
      when considering the relationship between observers to identify the actual
      coordinates of the same point.

PMID- 15457743
TI  - Growth, development and puberty indicators on spinal growth.

PMID- 15457744
TI  - Scoliosis study using finite element models.
AB  - Finite element models have been used for many years to study scoliosis
      biomechanics. This paper presents some of the work done in our institution over
      the last decade in this area. It covers the simulations of scoliosis treatment
      (orthotics, surgical instrumentation), muscle and control, as well as the growth
      process. The models presented in this paper are of clinical interest because they
      have the capacity to simulate an unlimited number of variables to investigate
      scoliosis biomechanics. Current developments are directed toward the integration
      and validation of specific models (muscle, control, and growth modeling) into a
      unified refined model of the trunk, thus allowing a more complete understanding
      of scoliotic spine pathomechanicsms, as well as to predict in advance what would
      be the resulting shape of the spine in response to the application of a treatment

PMID- 15457745
TI  - The role of muscles and effects of load on growth.
AB  - If mechanical modulation of growth explains progression of scoliosis during
      adolescent growth, two elements of the 'vicious cycle' must be quantified.
      Firstly we must identify the magnitude of the asymmetrical loading imposed on the
      spine as a function of the scoliosis curve magnitude. Secondly, we must
      characterize the growth response of vertebrae and remodeling response of discs to
      this asymmetrical loading. Animal models are helpful to quantify the former, and
      extrapolation to the human spine should be possible once the parameters that
      influence the growth modulation response have been identified. Direct measurement
      of spinal loading is not currently feasible, so analytical modeling to estimate
      plausible loading states is required. Our simulations using a model that
      represents the lumbar spinal musculature and a spine with increasing degrees of
      spinal curvature suggests that there is a range of muscle activation strategies
      that may predispose to progression by the 'vicious cycle' mechanism, but other
      strategies can load the spine uniformly, or even reverse the asymmetrical loading
      that would lead to progressive deformity. However, the latter strategies have a
      physiological 'cost' associated with increased muscle stress and increased spinal
      loading.

PMID- 15457746
TI  - Achondroplasia: 3D-CT evaluation of the cervical spine.

PMID- 15457747
TI  - Malformations of the craniocervical junction: 3D-CT evaluation.

PMID- 15457748
TI  - An experimental model of adult-onset slip progression in isthmic
      spondylolistesis.
AB  - Progressive spondylolisthesis may occur in adults with isthmic spondylolysis with
      an estimated incidence of 20%. This biomechanical study showed that in adult
      spines with bilateral L5 pars fractures, an anterior slip of L5 depends on the
      extent of the load-bearing deficiency of the disc and the presence of shear force
      across L5-S1. A combination of disc degeneration and muscle dysfunction may be
      responsible for converting a stable isthmic spondylolysis into an unstable
      progressive spondylolisthesis.

PMID- 15457749
TI  - The significance of correlation of radiographic variables and MOS short-form
      health survey for clinical decision in symptomatic low back pain patients.
AB  - OBJECTIVES: To assess any correlation between SF-36 scores and several lateral
      roentgenographic variables of the lumbar spine, both in low back pain patients
      and asymptomatic volunteers. The clinical relevance of the method proposed in
      this study to make a surgical strategy on the basis of distinct lateral
      roentgenographic parameters and conversely was assessed by independent
      radiologists and physicians. METHODS: One hundred asymptomatic male volunteers,
      used as controls and an equal number of age-, height- and weight- comparable
      consecutive patients with chronic low back pain were examined both
      roentgenographically and with the SF-36 questionnaire. The roentgenographic
      variables measured were: lumbar lordosis, sacral inclination, L1 to S1 vertebral
      inclination, L4-S1 distal lordosis, disc index, and L1 to L5 vertebral index.
      These variables were correlated with the eight SF-36 items both in patients and
      controls. Both sensitivity and specificity of the method were calculated to
      assess the impact of subjectivity on the clinical decision. RESULTS: Low back
      patients showed significantly lower scores than their asymptomatic counterparts,
      in physical role limitations (P<0.01), severity of bodily pain (P<0.01),
      interference of bodily pain (P<0.01) and mental health (P<0.001). In the
      controls, general health, physical functioning, social functioning, and role
      limitations displayed a statistically significant correlation with age, height,
      weight, lumbar lordosis, sacral inclination, inclination of L1,L3 & L5-vertebra,
      L1 to L5-vertebral index and L1-L2, L3-L4, L4-L5 and L5-S1 disc index. In LBP
      patients previous general health, physical functioning, role limitations, social
      functioning, bodily pain were significantly correlated with age, height, L1-and
      L2-inclination, distal lordosis, L5-index, and disc index L4-L5, and L5-S1.
      Although the consensus between either radiologists suggesting a strategy on the
      basis of roentgenographic data only or between physicians based on only SF-36
      data was significant (P<0.001), there was no consensus in clinical decision
      between physicians and radiologists. Clinical decision based on matched SF-36 and
      roentgenographic data made either by radiologists or surgeons showed significant
      correlations (P<0.001). However, both sensitivity and specificity of our method
      to make a clinical decision on the basis of radiology were low: 0.48 and 0.36
      respectively. CONCLUSIONS: SF-36 scores were correlated with distinct lateral
      roentgenographic variables of the lowermost lumbar spine (L4-S1) in low back
      patients, and of the whole lumbar spine in asymptomatic individuals. Clinical
      decision should not be taken on the basis of radiological evidence of pathology
      because clinical decision seems to be more accurate when is taken on the basis of
      combined SF-36 and roentgenographic data. However, clinical examination is
      mandatory to SF-36 questionnaire and radiographic analysis.

PMID- 15457750
TI  - Sciatic scoliosis, its natural history and the ability of the Mckenzie management
      to influence it.

PMID- 15457751
TI  - Pathomechanic basics of conservative treatment of progressive idiopathic
      scoliosis according to Dobosiewicz method based upon radiologic evaluation.
AB  - Conservative treatment of idiopathic scoliosis, especially kinesitherapy, is not
      widely appreciated due to its suspected low effectiveness in relation to a
      surgical treatment. After long-year assessment of patomechanics of scoliosis in
      Department of Rehabilitation of Medical University of Silesia a conservative
      method of treatment, asymmetric trunk mobilization in strictly symmetric
      positions, was developed. This method enables to detain progression of scoliosis,
      or even decrease lateral curvature of a spine and angle of rotation assuming
      adequate cooperation of patient and its family.

PMID- 15457752
TI  - Conservative management in patients with scoliosis--does it reduce the incidence
      of surgery?
AB  - The effectiveness of conservative scoliosis treatment, including bracing, is
      widely denied. Like any therapeutic intervention, conservative scoliosis
      treatment including patient education, techniques of brace moulding, and time
      consuming follow-ups is reasonable only if the benefits outweigh the strain
      placed upon the patient by the treatment. The most important benefit of early
      intervention in scoliosis is prevention of the need for spinal fusion surgery.
      Retrospective analysis of the incidence of surgery for patients with scoliosis,
      by comparison with incidence in an untreated control group. Since 1992 the
      bracing technique according to Cheneau has been applied in parallel with the
      scoliosis inpatient intensive rehabilitation programme (SIR). For this study we
      chose from our data base the scoliosis patients who had conservative treatment at
      our center between 1993 and 1996. All patients, like those of the control group,
      were at least 15 years of age at the time they were evaluated for the last time.
      The incidence of surgery of our group was compared with that reported by a center
      in Ireland. Of 343 female scoliosis patients with a curve angle of 33.4 AE
      (SD=18.9), 41 (11.95%) had surgery. The incidence of surgery of our collective
      was significantly lower than the incidence of surgery of the control group which
      reported an incidence of 28,1%. The AIS matched group of patients (n = 179) had
      an incidence of surgery of slightly more than 7%. When compared with a matched
      control group of untreated patients, incidence of surgery was significantly
      reduced by SIR combined with bracing. So conservative management is indicated in
      patients with scoliosis.

PMID- 15457753
TI  - Influence of method of asymmetric trunk mobilization on shaping of a
      physiological thoracic kyphosis in children and youth suffering from progressive
      idiopathic scoliosis.
AB  - Idiopathic scoliosis (IS), which is substantially a three-dimensional deformation
      of a spine, causes not only lateral curvature and axial rotation of vertebral
      column, but also lordotisation of vertebrae in structural curve extension. In an
      effect physiological thoracic kyphosis diminishes or even disappears. Method of
      asymmetric trunk mobilisation in strictly symmetric positions according to
      Dobosiewicz not only deteriorates progression of IS or even reduces lateral
      curvature, but also significantly rebuilds physiological thoracic kyphosis in
      cases of IS accompanied by straight back.

PMID- 15457754
TI  - Curvature progression in patients treated with scoliosis in-patient
      rehabilitation--a sex and age matched controlled study.
AB  - The aim of this study is to test the hypothesis that physiotherapy-based
      intervention can reduce incidence of progression in children with IS because
      progression of spinal curvature in patients with idiopathic scoliosis (IS) is of
      paramount concern in treatment strategies. Follow-up of the outcome of two
      prospective studies using the outcome parameter, incidence of progression (> or =
      5 degrees), in treated and untreated patient groups matched by age, sex, and
      degree of curvature at diagnosis. A six-week scoliosis in-patient rehabilitation
      (SIR) program offering patient-specific physiotherapy including intensive
      therapist-assisted exercise in diagnosis-matched groups. A followup home therapy
      regime is designed for each patient. Incidence of progression in groups of
      untreated patients ranged from 1.5-fold (71.2% vs 46.7%) to 2.9-fold (55.8% vs
      19.2%) higher than in groups of patients treated with SIR, even when SIR-treated
      groups included patients with more severe curvatures. Statistically, the
      differences were highly significant. Postural imbalance is a component of spinal
      curvature and can be a causative mechanism. However, efforts to test the
      hypothesis that physical therapies addressing postural imbalance can be used
      effectively in the treatment of IS have been limited. The results of this study
      indicate that a supervised program of exercise-based therapies can reduce
      incidence of progression in children with IS.

PMID- 15457755
TI  - Exercise efficiency of girls with idiopathic scoliosis based on the ventilatory
      anaerobic threshold.
AB  - The aim of the study was to estimate the exercise efficiency in the group of
      girls with idiopathic scoliosis based on the ventilatory anaerobic threshold
      (VAT). MATERIAL AND METHOD: The investigation comprised 58 girls with idiopathic
      scoliosis, aged 10-16 years; 32 girls (55.20/0) with double major scolioSiS and
      26 girls (44.8%) with single scoliosis. The girls were conservatively treated
      using Dobosiewicz method. The control group consisted of 31 healthy girls aged 10
      16 years. The exercise test was performed using cycle ergometer. During the
      exercise the gas exchange parameters were recorded (minute expiratory
      ventilation, minute oxygen consumption, carbon dioxide production). On the basis
      of recorded parameters VAT has been computed, using V-slope method. RESULTS: The
      following VAT values were obtained in the group with scoliosis: 20.7+3.05 ml
      O2/min/kg b.m.; in control group: 21.9+3.50 ml O2/minlkg b.m. The differences
      between girls with idiopathic scoliosis and control group were not statistically
      significant. CONCLUSIONS: I. The exercise efficiency of girls with idiopathic
      scoliosis conservatively treated using Dobosiewicz method is normal. 2. Such high
      level of the exercise efficiency of the studied group probably was due to
      intensive 3-D respiratory exercises of these girls.

PMID- 15457756
TI  - Side shift exercise for idiopathic scoliosis after skeletal maturity.
AB  - A total of 69 patients with idiopathic SCO1-OS-S who were treated only by side
      shift exercise after their skeletal maturity were reviewed. The average age at
      the beginning of the side shift was 16.3 years and the average follow-up period
      was 4.2 years. Size of the curve was 31.5 degrees +11.2 at the beginning of the
      side shift and 30.3-i12.3 at the final follow-up. The side shift exercise can be
      a useful treatment option for the management of idiopathic scoliosis after
      skeletal maturity.

PMID- 15457757
TI  - Reversal of the signs and symptoms of moderately severe idiopathic scoliosis in
      response to physical methods.
AB  - This report describes improved signs and symptoms of previously untreated
      symptomatic spinal deformity in an adult female diagnosed with moderately severe
      thoracic scoliosis at the age of .7 years. Current treatment initiated at the age
      of forty included massage therapy, manual traction, ischemic pressure, and
      comprehensive manipulative medicine (CMM). A left-right chest circumference
      inequity was reduced by >10 cm, in correlation with improved appearance of the
      ribcage deformity and a 40% reduction in magnitude of Cobb angle, which had been
      stable for 30 years. The changes occurred gradually over an eight-year period,
      with the most rapid improvement occurring during two periods when CMM was
      employed.

PMID- 15457758
TI  - Long-term effects of scoliosis.

PMID- 15457759
TI  - Quantitative measurement of spinal brace use and compliance in the treatment of
      adolescent idiopathic scoliosis.
AB  - The objective measurement of compliance with spinal bracing in adolescents with
      idiopathic scoliosis (AIS) is fundamental in the validation of clinical trials of
      bracing effectiveness, and in helping clinicians better understand reasons behind
      poor compliance. Current technology has been developed and tested for discrete,
      reliable and objective measurement of the times of day a brace is worn and
      consistency in its use. TLSOs were instrumented with data loggers measuring
      temperature at the skin/brace interface at 16 minutes intervals over a period of
      88 days; between routine follow up and without patient interference. 10 female
      patients (age 14 years, sd 1.1) with AIS using spinal bracing as part of their
      treatment regime took part in the study over 15 months. Skin/brace interface
      temperature during periods of wear in the UK was >30 degrees C, ambient 23
      degrees C, sd 4. Compliance ranged from 8-90%, average 65%. Patients tended to
      over estimate their compliance by 150% (sd 50%). There was no significant
      difference between weekday and weekend compliance but wear patterns differed.
      Nightwear was significantly greater than daywear. Patients with very good
      compliance only removed their brace for washing or exercise periods but where
      poor compliance was evident, the brace was only worn sporadically during the day.
      Temperature provides a clear signal of brace use and can be used for long-term
      data logging using discrete instrumentation, providing a tool to help identify
      and understand the reasons behind poor compliance.

PMID- 15457760
TI  - Is the Boston brace mechanically effective in AIS?
AB  - The application of three-point loading is thought to be the essential basis for
      effective bracing of adolescent idiopathic scoliosis. Care is taken to ensure
      that active pressure pad is located to provide maximum support to the apex of the
      scoliosis while minimizing its lordosising effect. Paradoxically, while cited as
      an essential factor in the design of braces, there is no consensus as to the
      importance of such loading to the clinical effectiveness of braces. It may be
      that braces are effective but that they are effective for reasons unrelated to
      mechanics. There are few studies that link brace mechanics and change in spinal
      alignment. Optimal bracing for AIS requires a much better understanding of the
      role of the mechanical support of braces used to treat AIS. Sixteen subjects, 3
      males and 13 females, were participated to this study to determine the
      correlation between quantity and quality of brace wear and treatment outcomes in
      AIS. This study showed that the target force levels set for the active pad in
      braces prescribed for the treatment of AIS vary considerably and that brace
      applies the desired load 25% of the prescribed time.

PMID- 15457761
TI  - A wearable networked embedded system for the treatment of scoliosis.
AB  - In order to study a physiotherapeutic approach to idiopathic scoliosis treatment
      a posture monitoring system is being built. The system is a small, lightweight,
      fully portable system capable of monitoring and providing feedback to a patient
      regarding their posture. Using the combination of accelerometer and
      electromagnetic technology, distance and angle measurements can be obtained for
      receivers placed strategically on the patient's back. This data is recorded for
      further analysis of the patient's progress and to provide immediate feedback to
      the patient on the status of their posture. Preliminary testing has shown that
      angular changes of one degree can be detected by the system and that the speed of
      the electromagnetic field detection has been increased ten times greater than the
      previous architecture.

PMID- 15457762
TI  - Curve progression and spinal growth in brace treated idiopathic scoliosis.

PMID- 15457763
TI  - Personalized biomechanical modeling of Boston brace treatment in idiopathic
      scoliosis.
AB  - The aim of this study was to describe how the Boston brace modify the scoliotic
      curvatures using a finite element (FE) model and experimental measurements. The
      experimental protocol, applied on 12 scoliotic girls, was composed of the
      pressure measurement at the brace-torso interface followed by two radiographic
      acquisitions of the patient's torso with and without brace. A 3D FE model of the
      trunk was built for each unbraced patient. The brace treatment was represented by
      two different modeling approaches: 1) using equivalent forces calculated from the
      measured pressures; 2) by an explicit personalized FE model of the brace
      (hexahedral elements) and its interface with the torso (contact elements). In the
      first model, measured brace forces less than 40N and up to 113N induced
      respectively less than 21% and up to 87% of real correction. Thoracic forces
      induced the main correction, affecting partially both lumbar and thoracic curves,
      in agreement with the literature. In the second model, the brace closing reduced
      the curves up to 35% of real correction. Contact reaction forces (16-79N) were
      similar to real brace forces (11-72N). The results suggested that other
      mechanisms than brace pads contribute to the equilibrium of the patients.
      Postural control by the muscular system remains a problem to address in a future
      study. The second model represented more realistically the load transfer from the
      brace to the spine than external forces application. With such model, it is
      expected to predict the effect of a brace before its design and manufacturing,
      and also to improve its design.

PMID- 15457764
TI  - Intelligent brace system for the treatment of scoliosis.
AB  - Measurement of the biomechanical effectiveness of a brace for the treatment of
      scoliosis has been hampered by the lack of compressive information about wear
      characteristics. Orthotists and orthopaedic surgeons believe that the
      effectiveness of bracing is correlated with the strap tensions. If the strap
      tensions can be maintained at the optimal level while patients wear their braces,
      a better treatment outcome may be obtained. However, strap tensions vary
      significantly during different activities. An intelligent brace system has been
      developed to control the strap tension so that the optimal prescribed level is
      maintained at all time. This system consists of an innovative strap tension
      transducer, a microcomputer unit and a motorized unit. The strap transducer has
      been developed with an accuracy +/- 1.0N in the range of 0 to 100N. An
      instrumented Boston brace was built to test the concept. When the strap tension
      was below 80% of the prescribed level for a 15 minutes interval, the
      microcomputer unit signaled the motor to tighten the strap. While the strap
      tension level was above 120% of the prescribed level for a 15 minutes interval,
      the motor reversed the direction. Laboratory testing results showed that the
      strap tension could be maintained at the optimal prescribed level.

PMID- 15457765
TI  - Spine-Straight device for the treatment of kyphosis.
AB  - Kyphosis is an excessive rounding of the upper spine. Its treatment depends upon
      the severity, the age of the patient and the levels of the spine that are
      affected. Early diagnosis is a key to providing optimal treatment. In a
      skeletally immature patient, an exercise program or bracing is the most commonly
      used treatment. However, the compliance of bracing for adolescents is poor and
      exercise training is labor intensive. The purpose of this study is to determine
      whether a Spine-Straight device can help patients to correct their kyphosis
      themselves and there by reduce back pain without the biomechanical support of a
      brace. The Spine-Straight device consists of an accelerometer and a microcomputer
      unit. The accelerometer is used to measure the kyphotic angle and the
      microcomputer unit controls a pager vibrator to alert patients when their posture
      exceeds personalized thresholds. The system was tested in the laboratory before
      used by subjects. The results were compared to back data obtained from a laser
      scanner imaging system. The maximum angle deviation between the laser scanner and
      the Spine-Straight device was 1.5 degrees. Two volunteers tested the systems for
      2 days. The accelerometer was placed at the T3 location and the microcomputer
      unit was carried during daily activities. The angle measurement was recorded at 1
      minute intervals during daily activity over a period of 2 days. The preliminary
      trials demonstrate subjects can improve their posture when feedback signals were
      provided.

PMID- 15457766
TI  - Study of vertebral morphology in Scheuermann's kyphosis before and after
      treatment.
AB  - Variation of vertebral morphology in Scheuermann's Kyphosis before and after
      orthopedic treatment is usually measured by the entity of the curve, using Cobb's
      method, and by vertebral wedging. But the lack of correlation between these
      parameters and the clinical evolution of the deformity, lead to the possibility
      of other alterations that can explain part of the kyphosis deformities before and
      after the treatment. In this group of alterations the inclination of anterior and
      posterior walls, that express the trapezoid deformity of vertebras, seem to be
      more reliable indicators of curve response to ortopedic treatment.

PMID- 15457767
TI  - Biomechanics of the conservative treatment in idiopathic scoliotic curves in
      surgical "grey-area".
AB  - The biomechanical behaviour of the spine significantly varies in relation to the
      age of the spine. Particularly, the elastic behaviour of the intervertebral discs
      has been proved to change during the spine growth, which changes the disc
      reaction to externally imparted forces. The biomechanical analysis of the G
      modulus of torsion rigidity of the intervertebral disc shows that the G values
      progressively increase through growth, which favours the progression of early
      scoliotic curves. At the same time, however, early structural scoliosis is more
      amenable to conservative treatment owing to the residual growth potential of the
      spine. Whereas indications to surgical treatment of scoliotic curves has been
      based upon the magnitude of the curves as measured according to the Cobb method,
      two additional factors affect the chance of correcting a scoliotic curve, The
      first is the residual growth potential of the vertebrae. In fact, a longer
      residual growth allows for external forces to be applied so as to change the
      growth model of the scoliotic spine, which ensures a stable correction of the
      deformity when these external forces are removed. The second is the magnitude of
      the elastic deformation of the intervertebral discs. It has been suggested that a
      deformation beyond the disc elastic behaviour, by producing hysteresis of the
      disc, renders the disc less susceptible to transferring the load to the
      neighbouring vertebral bodies, thus impairing remodelling. It ensues that both
      the age and the magnitude of rotation affects the success of conservative
      treatment and not only the magnitude in Cobb degrees. The curve localization adds
      to these two parameters, thoracic curves being stiffer than thoracolumbar and
      lumbar curves.

PMID- 15457768
TI  - Cell viability and the physical environment in the scoliotic intervertebral disc.

PMID- 15457769
TI  - Brain-stem dysfunction and idiopathic scoliosis.

PMID- 15457770
TI  - Finite element simulation of various strategies for CD correction.
AB  - The scoliosis surgery using the Cotrel-Dubousset instrumentation is a complex
      three dimensional correction. This surgery was first simulated for a given
      patient using a personalized finite element model: the geometry was extracted
      from a 3D stereoradiographic reconstruction and mechanical properties were
      personalized using lateral bending tests. Finally, three alternative surgical
      strategies were simulated in order to analyze their effects on spine
      postoperative configuration. First results are promising and should allow
      surgeons to objectively analyze various strategies or techniques.

PMID- 15457771
TI  - Idiopathic scoliosis. Segmental fusion with transpedicular screws.
AB  - The purpose of this study is to evaluate whether the surgical correction of the
      scoliotic curve with the use of segmental pedicle screw fixation system is
      effective. We studied 20 patients (19 girls, 1 boy) with a mean age of 14,6 years
      (range from 13 to 22). The spinal deformities were evaluated by Cobb method with
      anteroposterior and lateral bending radiographs. There were 13 right thoracic
      curves and 7 left thoracolumbar curves. The width of the pedicles was estimated
      in all patients by computerized tomography of the thoracic and lumbar spine.
      Posterior instrumentation (Moss-Miami transpedicular system) was used and
      additional thoracoplasty was performed in 2 patients. The transpedicular screws
      were placed between T2 and L5. Intraoperatively the image intensification was
      indispensable and the wake-up test was always conducted. All the patients were
      assessed both clinically and radiographically at 3,6,9,12 months and annually
      until now. The average follow-up was two years. There was an average correction
      of 73% of the primary curve (pre-op standing average 59 degrees (range from 42
      degrees to 87 degrees), lateral bending average 33 degrees (range from 10 degrees
      to 75 degrees), post-op average 13 degrees (range from 6 to 30 degrees), at last
      examination average 14 degrees (range from 6 degrees to 33 degrees). Infection
      and neurological complications were not noted. No major complications were
      observed. Exact evaluation of the pedicles by CT scan is an essential
      prerequisite for transpedicular screw insertion. The correction of idiopathic
      curves with the use of segmental pedicle screw fixation system is a very
      effective method(correction > 70%) It seems that control of the three columns of
      the spine by the transpedicular screws offers sufficient apical translation and
      coronal realignment.

PMID- 15457772
TI  - Spinal surgery procedure discretization.
AB  - In the last decades, scientists developed analytic models of spinal surgery to
      assess surgical choices and instrumentation parameters. They noted the difficulty
      to represent the boundary conditions on their deterministic models and recognize
      the lack of knowledge in surgical procedures. This paper presents a formalization
      technique applied to spinal surgery to improve the formulation of biomechanical
      models. This technique consisted into two steps: knowledge extraction and
      knowledge representation. The protocol was established with an expert surgeon
      using Colorado2 instrumentation. Surgeon's knowledge acquisition has permitted to
      define eleven detailed independent data cards for the different steps of surgery
      like hook or screw insertion, rod installation, etc... The behaviour of the
      concerned elements on its neighbouring entity were specified using three
      matrices. The link between surgery and modelling becomes easier and permits to
      better define the boundary conditions on each entity during the simulation.

PMID- 15457773
TI  - Surgical treatment of scoliosis in myelomeningocele.
AB  - The high incidence and rapid progression of scoliosis in myelomeningocele make it
      one of the most disabling aspects of such disease. The choice of the surgical
      procedure to treat scoliosis in myelomeningocele is related to the peculiar
      features of this deformity. The purpose of this study is to review the results
      obtained by means of various surgical techniques and verify if posterior fusion
      with pedicle screws can improve results as compared to the single posterior
      approach. Patients were classified into three groups defined by treatment
      approach. The single posterior approach following either the Harrington or the
      Harrington-Luque technique yielded the least satisfactory results. The two-stage
      anterior-posterior spinal fusion provided good correction and stability.
      Correction and instrumented fusion through a single posterior approach with
      segmental fixation by means of pedicle screws proved to be valid and reliable,
      even when severe deformities had to be corrected and fused. In these latter cases
      pelvic fixation using ilio-sacral plates also made it possible to correct and
      stabilize pelvic obliquity.

PMID- 15457774
TI  - Use of a transpedicular drill guide for pedicle screw insertion in the thoracic
      spine.
AB  - A transpedicular drill guide (TDG) was designed to assist in the safe placement
      of pedicle screws in the thoracic spine. In a preliminary study, pilot holes were
      drilled into the pedicles (T1 to T12) of eight anatomical models in order to
      compare the conventional anatomical technique to the TDG. Visual inspection of
      the drilled pedicles was performed. Subsequently in a cadaveric study, pilot
      holes were made using the TDG in the thoracic spine (T1 to T11) of one human
      cadaver before inserting 4.5 mm diameter screws. CT scan followed by visual
      inspection of the cadaveric spine was performed to evaluate the position of the
      screws. With the anatomical models, 19 of 96 (19.8%) holes drilled using the TDG
      and 64 of 96 (66.7%) holes drilled using the anatomical technique violated the
      pedicle wall (p<0.001). The TDG reduced the rate of medial perforation. Ninety
      nine percent of the pilot holes made with the TDG were within 2 mm from the
      pedicle wall compared to 79.2% for the anatomical technique. In the cadaveric
      study, one of the 22 (4.5%) screws violated the medial wall of the right T1
      pedicle by less than 1 mm. No screw penetrated the anterior vertebral cortex, nor
      the lateral, superior or inferior pedicle wall. The TDG is easy to use and can
      decrease the incidence of misplaced thoracic pedicle screws. The TDG could be
      used alone as an alternative to navigation systems in certain applications or
      with fluoroscopy during thoracic pedicle screw placement, especially for training
      surgeons.

PMID- 15457775
TI  - Surgical management of a congenital kyphotic deformity in an adolescent.
AB  - This is a case of an adolescent with kyphoscoliosis due to congenital partially
      segmented vertebrae T12, L1, L2 who was treated operatively by a back-front-back,
      one stage operation. A 16 year old patient neurologically intact with a rounded
      gibbous in the lower thoracic region and a mild scoliotic element had no other
      congenital anomaly. His kyphotic deformity was 85 degrees measured with the Cobb
      method. Preoperatively, a CT and MRI scan of the spine was performed and a three
      level anterolateral failure of segmentation in the thoracic spine was diagnosed
      without spinal dysraphism. The operation lasted 8 hours and the Moss-Miami
      anterior and posterior fixation systems were used for fusion from T10 to T4. It
      included initially posterior approach for transpendicular screw insertion, wedge
      resection of the posterior elemens followed by anterior approach (thoracotomy),
      osteotomy of the defected vertebrae, anterior correction and fusion T11 to L1 and
      final correction with rod placement posteriorly. The wake-up test was performed
      twice. The follow-up was 3 years. The postoperative correction of the kyphosis
      was 45% (42 degrees) and there was practically no loss of correction in the last
      follow-up. No complications were observed. Detailed preoperative assessment of
      the patients with congenital deformities is essential in order to establish the
      correct diagnosis and choose the proper treatment. Substantial kyphotic
      deformities require combined antero-posterior procedures.

PMID- 15457776
TI  - The role of rigid vs. dynamic instrumentation for stabilization of the
      degenerative lumbosacral spine.
AB  - PURPOSE OF THE STUDY: This is a prospective comparative randomised study to
      compare the immediately postoperative effects of a rigid versus dynamic
      instrumentation for degenerative spine disease and stenosis on the standing
      sagittal lumbar spine alignment and to investigate if a dynamic spine system can
      replace the commonly used rigid systems in order to avoid the above mentioned
      disadvantages of rigid fixation. MATERIAL & METHODS: 15 randomly selected
      patients received the rigid instrumentation SCS and an equal number of randomly
      selected patients the dynamic TWINFLEX device for spinal stenosis associated
      degenerative lumbar disease. The age of the patients, who received rigid and
      dynamic instrumentation was 65 +/- 9 years and 62 +/- 10 years respectively. All
      patients had standing spine radiographs preoperatively and three months
      postoperatively. The parameters that were measured and compared pre- to
      postoperatively were: lumbar lordosis (L1-S1), total lumbar lordosis (T12-S1),
      sacral tilt, distal lordosis (L4-S1), intervertebral angulation, vertebral
      inclination and disc index. RESULTS: The instrumented levels in the spines that
      received rigid and dynamic instrumentation were 3.5 +/- 0.53 and 3 +/- 0.7
      respectively. The instrumented levels from L3 to L5 were 23, the lumbosacral
      junction was instrumented in 3 patients of group A and in 4 patients of group B.
      Lumbar lordosis did not significantly change postoperatively, while total
      lordosis was significantly (P=0.04) increased in the patients who received the
      rigid instrumentation, while it was significantly (P=0.012) decreased in the
      group B. Intervertebral angulation of the non-instrumented level L1-L2 was
      increased in the group A (P=0.01), while the dynamic instrumentation increased
      (P=0.02) the intervertebral inclination of the adjacent level L2-L3, immediately
      above the uppermost instrumented level. Distal lordosis and sacral tilt did not
      change in any patient in both groups. Both instrumentations did not change the
      lateral vertebral inclination of L1 to L5 vertebrae. Rigid instrumentation
      increased the lordotic inclination of L5 (P=0.03) and of S1 (P=0.03). Rigid
      instrumentation increased (P=0.04) the intervertebral angulation at the uppermost
      instrumented level L3-L4 The most significant change in vertebral angulation was
      achieved at the instrumented level L4-L5 by the dynamic (P=0.007) and rigid
      (0.05). The disc index at the level L2-L3 was increased by both instrumentation
      [dynamic P=0.007 and rigid (P=0.02)]. The index L3-L4 was increased following
      dynamic fixation (P=0.0007). The disc index L4-L5 was postoperatively increased
      by both types of instrumentation (rigid P=0.006, dynamic P=0.02). The disc index
      L5-S1 did not significantly change postoperatively by either system. CONCLUSION:
      Both rigid and dynamic instrumentations restored lumbar lordosis, sacral tilt,
      distal lordosis and increased the foraminal diameter at the level L4-L5 resulting
      in an indirect decompression of the nerve roots at this level . Both rigid and
      dynamic instrumentations applied in the lumbosacral spine to treat degenerative
      disease secured L3 to S1 sagittal spine profile close to preoperative levels,
      that should theoretically guarantee a pain-free postoperative course. This study
      supports the belief that the dynamic system can be used with the same indications
      with the rigid in degenerative lumbar spine because it can offer equally good
      short-term results regarding sagittal spine alignment while simultaneously it has
      the previously mentioned advantages (avoidance stress shielding etc).

PMID- 15457777
TI  - Spine deformity correlates better than trunk deformity with idiopathic scoliosis
      patients' quality of life questionnaire responses.
AB  - AIM: To determine whether either spine or trunk deformity measurements correlate
      with patients quality of life questionnaire responses. MATERIALS AND METHODS:
      Forty five pre operative patients (5M, 40F), average age 15 years, 9 months
      (range, 10-20) met the inclusion criteria of age (< or = 20 years), Posterior
      Trunk Symmetry Index (POTSI) and Suzuki Hump Sum (SHS) determination from surface
      topography, and Scoliosis Research Society-22 (SRS-22)patient questionnaire
      completion. Average measurement and measurement ranges were largest Cobb 62
      degrees (range, 40-137 degrees), POTSI 49 (range, 17-149), SHS 16 (5-32), and SRS
      22 subtotal score 3.86 (range, 4.7-2.35). The individual SRS-22 domain scores
      were function 4.13 (4.80-2.20), pain 4.01 (5-1.60), self image 3.34 (4.4-1.80)
      and mental health 4.01 (5-1.80). (Scale 5 Best-1 Worst). Correlations between
      deformity and questionnaire measurements were determined, p<0.01 considered
      significant. RESULTS: Spine deformity (Cobb) correlated with the SRS-22 subtotal
      scores (cc-04207, p<0.005) and with the function and self image SRS-22 domain
      scores: cc0.5182, p<0.001) and cc-0.3981, p<0.01 respectively. Neither trunk
      deformity score correlated with the SRS-22 Score: POTSI versus SRS-22 (cc 0.0449,
      ns) and SHS versus SRS-22 (cc-0.0311, ns) CONCLUSION: Spine deformity correlates
      well with quality of life questionnaire responses whereas trunk deformity
      magnitude does not. This is somewhat surprising as it is the trunk deformity that
      the patient can they themselves see. These findings illustrate the pitfalls of
      assuming what is important to the patient based on clinical measurements.

PMID- 15457778
TI  - The rib hump after surgery for early onset spinal deformity.
AB  - Spinal deformity presenting early in childhood has a poor prognosis, in that
      progression is probable and severe respiratory compromise is a real possibility.
      Treatment is difficult, since these patients frequently do not respond to
      bracing, and surgery is sometimes performed in childhood in an attempt to control
      relentless progression. This carries the risk of continued deformation during
      subsequent growth, and the surgical procedures have been adapted in an attempt to
      minimise this. 25 children undergoing spinal fusion for progressive and severe
      deformity have sequential topographic scans which show that, despite measures to
      control the rib hump, progression after surgery is the rule.

PMID- 15457779
TI  - Trunk deformity correction stability following posterior instrumentation and
      arthrodesis for idiopathic scoliosis.
AB  - AIM: To determine whether trunk deformity correction is stable over time.
      MATERIALS AND METHODS: Thirty-seven patients (5M, 32 F) average age 16 years, 3
      months (range, 10 to 38) met inclusion crieteria of primary posterios
      instrumentation (ISOLA) and arthrodesis with x-ray and surface topography
      measurements [Posterior Trunk Symmetry Index (POTSI)] and [Suzuki Hump Sum (SHS)]
      pre-operatively and at 2 years follow up. For 30 patients measurements were also
      available post-operatively. Patient's average pre, post, and two-year
      measurements were: Largst Cobb 65 degrees (+/- 12), 21 degrees (+/- 8), and 21
      degrees (+/- 17); POTSI 53 (+/- 29), 28 (+/- 12); and 22 degrees (+/- 10); and
      SHS 18 (+/- 11), 12 (+/- 7), and 12 (+/- 7), and 12 (+/- 6). Statistical analysis
      was done with the sign test, comparing only patients with data at the intervals
      studied. Surface topography measurements were considered to be unchanged/tied
      unless they increased or decreased by more than 8 for POTSI and 3.5 for SHS,
      Significance was set at p<0.05. RESULTS: POTSI changes were pre-to post
      operative: 20 improved (I), 3 worsened (W), and 7 tied (T) (p<0.01): pre to two
      years: 30 (I), 4 (W), and 3 (T) (p<0.01): and from post to two years: 14 (I), 3
      (W) and 13 (T) (p<0.01). SHS changes were pre to post to two years: 18 (I), 2
      (W), and 11 (T) (p<0.01); pre to two years: 23 (I), 2 (W), and 11 (T) (p<0.01);
      ad post to two years: 4(I), 6 (W), and 20 T (ns). CONCLUSION: Trunk deformity
      improvement following surgery is stable or improved over time with surgical
      techniques utilized.

PMID- 15457780
TI  - Anterior universal spine system for adolescent idiopathic scoliosis: a follow-up
      study using scoliometer, real-time ultrasound and radiographs.
AB  - Nine patients with AIS treated surgically with anterior USS instrumentation were
      examined by several methods pre-operatively and at each of 8 weeks, 1 year and 2
      years after surgery (mean age 14.6 years, girls 7, boys 2, thoracolumbar 7,
      lumbar 1, thoracic 1, left 7, right 2). The methods used were (1) Scoliometer to
      measure angle of trunk inclinations (ATIs) in the standing forward bending
      position at each of 10 levels and converted to 18 levels by a computer program,
      (2) real-time ultrasound in the prone position of laminal rotations at each of 1
      8 levels from TI-SI, and (3) anteroposterior radiographs in the standing erect
      position measured for each of Cobb angle, segmental vertebral rotation
      (Perdriolle) and segmental vertebral translation from the Ti-Si line (horizontal
      translation of each vertebral centroid from the T1-S1 line). The findings were
      plotted graphically and segmentally for each of Scoliometer ATJs, ultrasound
      laminal rotations, and radiographic vertebral rotations and translations.
      Findings. Graphical representation of the data shows that the improvement brought
      about by surgery is most clearly and consistently evident for segmental vertebral
      translation. The statistical analysis shows that the radiological parameters
      (Cobb angle, apical vertebral rotation and apical vertebral translation) and
      ultrasound spinal (laminal) rotation do not change detectably in follow-up. The
      Scoliometer ATI findings show an increase from 4 degrees (at 8 weeks) to 7
      degrees (at 2 years) which is statistically significant. The evidence from this
      small sample of patients is consistent with the view that the compared with
      posterior USS, anterior USS surgery for AIS results in (1) similar initial rib
      hump correction, and (2) less rib hump reassertion during follow-up. More data
      are needed to evaluate these views.

PMID- 15457781
TI  - Long-term follow-up of surgically treated AIS patients.
AB  - The aim of this study was to determine the long-term changes in spine and trunk
      alignment in patients who have undergone scoliosis surgery. Twenty-three (16F;
      7M; at age of surgery 15.7 +/- 4.9 years) patients with adolescent idiopathic
      scoliosis agreed to participate and had posterior-anterior radiographs and
      surface topography prior to derotation surgery, within 6 months of surgery, at 2
      years post-operatively and 5-10 years (mean follow-up period 6.11 +/- 1.6 years)
      after surgery. Cobb angles, surface trunk rotations, and cosmetic scores were
      measured at each visit. A questionnaire assessed back appearance and pain at the
      5-10 year follow-up. The results of the questionnaire were compared to 25
      patients with idiopathic scoliosis who had recently undergone surgery. A paired
      two-tailed Student's t-test with p=0.05 was used to compare the deformity between
      visits. The Cobb angle and cosmetic score improved after surgery while the change
      in trunk rotation was insignificant (p=0.37). Between the two-year and 5-10 year
      review, the Cobb angle, cosmetic score, and surface trunk rotation significantly
      increased. Self-perception of appearance and pain were similar to the control
      group. Surgical correction of scoliosis is not completely maintained during
      adulthood although the radiographic and surface deterioration does not appear to
      be clinically significant.

PMID- 15457782
TI  - Assessing the impact of pelvic obliquity in post-operative neuromuscular
      scoliosis.
AB  - The goal of this pilot study was to explore the relationship between pelvic
      obliquity and patient pain, sitting tolerance, pressure sores, and function. Five
      neuromuscular patients who underwent spinal surgery 6-26 weeks prior to
      assessment took part in this on-going study (4F; 1M); age at surgery (14.6 +/-
      2.6 years). Pelvic obliquity was measured from pre- and post-operative anterior
      posterior radiographs. A force-sensing pad with a grid of sensors was placed on a
      flat surface and the weight distribution pattern was recorded. The pressures were
      divided into left and right sides and peak levels were noted on each side. The
      parents or caregivers completed a questionnaire on their child's pain, sitting
      tolerance, pressure sores, and functional abilities. Pelvic obliquity was reduced
      after surgery by approximately 50% depending on the method used to assess pelvic
      obliquity. The major curve was reduced from 64 degrees(10 degrees) to 39 degrees
      (10 degrees). Post operatively, the average pressure (left/right side) ranged
      from 1.2 to 2.0 (average 1.6). The peak pressure ratio ranged from 1.1 to 1.9
      (average 1.4). The ratio of left/right pressure correlated with improvement in
      pelvic obliquity (r2=0.9). Pain was moderate/severe in the 2 patients with the
      least correction as measured with the Cobb angle from surgery; both improved
      following surgery. Two patients suffered pressure sores pre-operatively and one
      post-operatively. Only 3/5 felt sitting endurance had increased. All parents felt
      their child sat straighter after surgery. The outcome measures of pain, pressure
      sores, sitting tolerance, and function were not well related to the amount of
      pelvic obliquity. More candidates and a longer follow-up may shed light on the
      many relationships.

PMID- 15457783
TI  - Is this as good as it gets? It may be.

PMID- 15457784
TI  - Modification of the spinal peak growth velocity as a possible treatment for adult
      scoliosis.

PMID- 15457785
TI  - Outcomes of scoliosis fusion--is stiff and straight better?

PMID- 15457786
TI  - Climate change: why should water professionals care?

PMID- 15457787
TI  - What's new with CUASHI?

PMID- 15457788
TI  - Can the desert bloom? Lessons learned from the Israeli case.
AB  - Despite the central management of Israel's water resources and the highly planned
      strategy for a sustainable water supply, Israel has twice faced an acute water
      crisis during the past decade. Although the visible problem is related to a lack
      of additional quantities of water, the deterioration of water quality appears to
      be endangering the future use of available water quantities as well. A long-term
      policy of ground water mining (translated to salt water encroachments), and
      irrigation with relatively saline water and recycled waste water, among other
      damage, account for this deterioration. Enhanced flushing of the salt and
      contaminant load from the aquifers (using various techniques) is proposed as a
      solution to the problem.

PMID- 15457789
TI  - Modeling multiscale heterogeneity and aquifer interconnectivity.
AB  - A number of methods involving indicator geostatistics were combined in a
      methodology for characterizing and modeling multiscale heterogeneity. The
      methodology circumvents sources of bias common in data from borehole logs. We
      applied this methodology to the complex heterogeneity within a regional system of
      buried valley aquifers, which occurs in the western glaciated plains of North
      America and includes the Spiritwood Aquifer. The region is conceptualized as
      having a hierarchical organization with three facies assemblage types (large
      scale heterogeneity) and two facies types within each assemblage (small-scale
      heterogeneity). We statistically characterized the sedimentary architecture at
      both scales, formulated indicator correlation models from those
      characterizations, and used the models to simulate the architecture in a
      multiscale realization. We focused on the interconnectivity of units creating
      higher-permeability pathways. Higher-permeability pathways span the realization
      even though the proportion of higher-permeability facies is less than the
      percolation threshold. Thus, geologic structures as represented in the indicator
      correlation models create interconnectivity above that which would occur if the
      higher-permeability facies were randomly placed. This amount of interconnection
      among higher-permeability facies within the multiscale realization is consistent
      with that suggested in prior hydraulic and geochemical studies of the regional
      system.

PMID- 15457790
TI  - Integrated geophysical and chemical study of saline water intrusion.
AB  - Surface geophysical surveys provide an effective way to image the subsurface and
      the ground water zone without a large number of observation wells. DC resistivity
      sounding generally identifies the subsurface formations-the aquifer zone as well
      as the formations saturated with saline/brackish water. However, the method has
      serious ambiguities in distinguishing the geological formations of similar
      resistivities such as saline sand and saline clay, or water quality such as fresh
      or saline, in a low resistivity formation. In order to minimize the ambiguity and
      ascertain the efficacy of data integration techniques in ground water and saline
      contamination studies, a combined geophysical survey and periodic chemical
      analysis of ground water were carried out employing DC resistivity profiling,
      resistivity sounding, and shallow seismic refraction methods. By constraining
      resistivity interpretation with inputs from seismic refraction and chemical
      analysis, the data integration study proved to be a powerful method for
      identification of the subsurface formations, ground water zones, the subsurface
      saline/brackish water zones, and the probable mode and cause of saline water
      intrusion in an inland aquifer. A case study presented here illustrates these
      principles. Resistivity sounding alone had earlier failed to identify the
      different formations in the saline environment. Data integration and resistivity
      interpretation constrained by water quality analysis led to a new concept of
      minimum resistivity for ground water-bearing zones, which is the optimum value of
      resistivity of a subsurface formation in an area below which ground water
      contained in it is saline/brackish and unsuitable for drinking.

PMID- 15457791
TI  - Use of Rhodamine water tracer in the marshland upwelling system.
AB  - Rhodamine water tracer (RWT) was used to characterize the migration of waste
      water within the saline subsurface of a marshland upwelling system (MUS), which
      is an alternative on-site waste water treatment system for coastal areas. Field
      tracer studies were performed to investigate the fresh waste water plume movement
      within the saline ground water. Pore velocities were calculated using first
      detection times and ranged from 0.68 to 10.7 x 10(-4) cm/sec for the loamy sandy
      soil matrix present at the site. Use of RWT in the field also allowed
      determination of main and preferential flowpaths. One- and two-dimensional
      laboratory experiments were performed using silica sand to investigate the
      interactions of the organically rich waste water with RWT within the zone
      surrounding the point of injection (one-dimensional) and the impact of background
      salinity on plume movement (two-dimensional). The results from these studies were
      used to help explain the field data. One-dimensional breakthrough curves revealed
      retardation factors for the RWT in the waste water mixture of 1.73 to 1.90. These
      results were similar to other researchers, indicating little interaction between
      the waste water and RWT. Variations in pore water salinity (5, 15, 25, and 35
      ppt) were found to have a significant effect on pore water velocities of the
      fresh water plume (two-dimensional), indicating the need to incorporate
      background salinities into the design process for MUS.

PMID- 15457792
TI  - A method for evaluating horizontal well pumping tests.
AB  - Predicting the future performance of horizontal wells under varying pumping
      conditions requires estimates of basic aquifer parameters, notably transmissivity
      and storativity. For vertical wells, there are well-established methods for
      estimating these parameters, typically based on either the recovery from induced
      head changes in a well or from the head response in observation wells to pumping
      in a test well. Comparable aquifer parameter estimation methods for horizontal
      wells have not been presented in the ground water literature. Formation parameter
      estimation methods based on measurements of pressure in horizontal wells have
      been presented in the petroleum industry literature, but these methods have
      limited applicability for ground water evaluation and are based on pressure
      measurements in only the horizontal well borehole, rather than in observation
      wells. This paper presents a simple and versatile method by which pumping test
      procedures developed for vertical wells can be applied to horizontal well pumping
      tests. The method presented here uses the principle of superposition to represent
      the horizontal well as a series of partially penetrating vertical wells. This
      concept is used to estimate a distance from an observation well at which a
      vertical well that has the same total pumping rate as the horizontal well will
      produce the same drawdown as the horizontal well. This equivalent distance may
      then be associated with an observation well for use in pumping test algorithms
      and type curves developed for vertical wells. The method is shown to produce good
      results for confined aquifers and unconfined aquifers in the absence of delayed
      yield response. For unconfined aquifers, the presence of delayed yield response
      increases the method error.

PMID- 15457793
TI  - Ground water flow parameterization of an Appalachian coal mine complex.
AB  - We examined a large (240 km2) northern Appalachian bituminous coal basin (Irwin
      Syncline, Westmoreland County, Pennsylvania) comprising 27 mine complexes with
      nine major (> 2.5 x 10(3) L/min) discharges. The synclinal basin was divided into
      seven subbasins based on equilibrium hydraulic relationships established during
      the past 25 years. Recharge rates, mine pool velocity, and residence times
      respond to hydraulic changes in the overburden induced by mine subsidence. The
      estimated maximum depth for subsidence fractures is 60 m (30 times mined
      thickness) with recharge rates decreasing significantly in subbasins with thicker
      overburden (> 75 m). Calculated subbasin recharge rates range from 2 to 6 x 10(
      4) L/min/m2 and are significantly lower than the previously used rate for the
      basin. Residence time of ground water in the Irwin subbasins calculated using
      average linear velocity ranged from one to five years and were more consistent
      with field observations than estimates obtained using discharge and basin volume
      area. A positive correlation (r2 = 0.80) exists between net alkalinity of the
      mine water-impacted discharges and residence time in the mine pools. Our results
      for the Irwin coal basin suggest that use of a subbasin approach incorporating
      overburden depth, mining methodology, and the extent of postmining inundation
      will lead to improved determination of ground water flow parameters in mined
      watersheds in northern Appalachia and elsewhere.

PMID- 15457794
TI  - Sequential analysis of hydrochemical data for watershed characterization.
AB  - A methodology for characterizing the hydrogeology of watersheds using
      hydrochemical data that combine statistical, geochemical, and spatial techniques
      is presented. Surface water and ground water base flow and spring runoff samples
      (180 total) from a single watershed are first classified using hierarchical
      cluster analysis. The statistical clusters are analyzed for spatial coherence
      confirming that the clusters have a geological basis corresponding to topographic
      flowpaths and showing that the fractured rock aquifer behaves as an equivalent
      porous medium on the watershed scale. Then principal component analysis (PCA) is
      used to determine the sources of variation between parameters. PCA analysis shows
      that the variations within the dataset are related to variations in calcium,
      magnesium, SO4, and HCO3, which are derived from natural weathering reactions,
      and pH, NO3, and chlorine, which indicate anthropogenic impact. PHREEQC modeling
      is used to quantitatively describe the natural hydrochemical evolution for the
      watershed and aid in discrimination of samples that have an anthropogenic
      component. Finally, the seasonal changes in the water chemistry of individual
      sites were analyzed to better characterize the spatial variability of vertical
      hydraulic conductivity. The integrated result provides a method to characterize
      the hydrogeology of the watershed that fully utilizes traditional data.

PMID- 15457795
TI  - Full-Bayesian inversion of the Edwards Aquifer.
AB  - The Bayesian inverse approach proposed by Woodbury and Ulrych (2000) is extended
      to estimate the transmissivity fields of highly heterogeneous aquifers for steady
      state ground water flow. Boundary conditions are Dirichlet and Neumann type, and
      sink and source terms are included. A first-order approximation of Taylor's
      series for the exponential terms introduced by sinks and sources or the Neumann
      condition in the governing equation is adopted. Such a treatment leads to a
      linear finite element formulation between hydraulic head and the logarithm of the
      transmissivity-denoted as ln(T)-perturbations. An updating procedure similar to
      that of Woodbury and Ulrych (2000) can be performed. This new algorithm is
      examined against a generic example. It is found that the linearized solution
      approximates the true solution with an R2 coefficient = 0.96 for an ln(T)
      variance of 9 for the test case. The addition of hydraulic head data is shown to
      improve the ln(T) estimates, in comparison to simply interpolating the sparse
      ln(T) data alone. The new Bayesian code is also employed to calibrate a high
      resolution finite difference MODFLOW model of the Edwards Aquifer in southwest
      Texas. The posterior ln(T) field from this application yields better head fit
      when compared to the prior ln(T) field determined from upscaling and cokriging.
      We believe that traditional MODFLOW grids could be imported into the new Bayes
      code fairly seamlessly and thereby enhance existing calibration of many aquifers.

PMID- 15457796
TI  - A practical model for mobile, residual, and entrapped NAPL in water-wet porous
      media.
AB  - Flow of nonvolatile nonaqueous phase liquid (NAPL) and aqueous phases that
      account for mobile, entrapped, and residual NAPL in variably saturated water-wet
      porous media is modeled and compared against results from detailed laboratory
      experiments. Residual saturation formation in the vadose zone is a process that
      is often ignored in multifluid flow simulators, which might cause an
      overestimation of the volume of NAPL that reaches the ground water. Mobile NAPL
      is defined as being continuous in the pore space and flows under a pressure
      gradient or gravitational body force. Entrapped NAPL is defined as being occluded
      by the aqueous phase, occurring as immobile ganglia surrounded by aqueous phase
      in the pore space and formed when NAPL is replaced by the aqueous phase. Residual
      NAPL is defined as immobile, nonwater entrapped NAPL that does not drain from the
      pore spaces and is conceptualized as being either continuous or discontinuous.
      Free NAPL comprises mobile and residual NAPL. The numerical model is formulated
      on mass conservation equations for oil and water, transported via NAPL and
      aqueous phases through variably saturated porous media. To account for phase
      transitions, a primary variable switching scheme is implemented for the oil-mass
      conservation equation over three phase conditions: (1) aqueous or aqueous-gas
      with dissolved oil, (2) aqueous or aqueous-gas with entrapped NAPL, and (3)
      aqueous or aqueous gas with free NAPL. Two laboratory-scale column experiments
      are modeled to verify the numerical model. Comparisons between the numerical
      simulations and experiments demonstrate the necessity to include the residual
      NAPL formation process in multifluid flow simulators.

PMID- 15457797
TI  - Analytical and numerical models to explain steady rates of spring flow.
AB  - Flow from some springs in former glacial lakebeds of the Upper Midwest is
      extremely steady throughout the year and does not increase significantly after
      precipitation events or seasonal recharge. Analytical and simplified numerical
      models of spring systems were used to determine whether preferential ground water
      flow through high-permeability features in shallow sandstone aquifers could
      produce typical values of spring discharge and the unusually steady rates of
      spring flow. The analytical model is based on a one-dimensional solution for
      periodic ground water flow. Solutions to this model suggest that it is unlikely
      that a periodic forcing due to seasonal variations in areal recharge would
      propagate to springs in a setting where high-permeability features exist. The
      analytical model shows that the effective length of the aquifer, or the length of
      flowpaths to a spring, and the total transmissivity of the aquifer have the
      greatest potential to impact the nature of spring flow in this setting. The
      numerical models show that high-permeability features can influence the magnitude
      of spring flow and the results demonstrate that the lengths of ground water
      flowpaths increase when high-permeability features are explicitly modeled, thus
      decreasing the likelihood for temporal variations in spring flow.

PMID- 15457798
TI  - Scale effect and calibration of contaminant transport models.
AB  - The influence on solute transport of the small-scale spatial variation of aquifer
      hydraulic conductivity (K) was analyzed by comparing results from fine-grid (2 m
      by 2 m) simulations of a synthetic heterogeneous aquifer to those from coarse
      grid (8 m by 4 m) simulations of an equivalent homogeneous aquifer. Realizations
      of the K field of the heterogeneous aquifer were generated, using the Monte Carlo
      approach, from a lognormal distribution with mean log K of 2 (K in m/d) and three
      levels of log K variance of 0.1, 0.5, and 1.0. Numerical simulation results show
      that the average standard deviation of point concentrations increased from 1.21
      to 5.78 when the value of log K variance was increased from 0.1 to 1.0. The
      average discrepancy between modeled concentrations (obtained from a coarse-grid
      deterministic numerical simulation) and the actual mean point concentrations
      (obtained from fine-grid Monte Carlo numerical simulations) increased from 0.91
      to 4.23 with the increase in log K variance. The results from this study
      illustrate the uncertainty in predictions from contaminant transport models due
      to their inability to simulate the effects of heterogeneities at scales smaller
      than the model grid.

PMID- 15457799
TI  - Transport of pharmaceutically active compounds in saturated laboratory columns.
AB  - Occurrences of pharmaceutically active compounds in surface water and sewage
      water have been widely reported. Investigations show the presence of several
      classes of pharmaceuticals such as antirheumatics (e.g., diclofenac), analgesics
      (e.g., propyphenazone), and blood lipid regulators (clofibric acid), even in
      ground water. Compared to their occurrences in surface water, however, the
      reported incidences of drugs in ground water are much rarer. This may be due to
      the input, but also to transport processes and degradation in the aquifer. In
      field studies investigating ground water sampled at a bank infiltration site at
      Lake Tegel, Berlin, Germany, clofibric acid was found at concentrations up to 290
      ng/L, and propyphenazone up to 250 ng/L, whereas concentrations of diclofenac
      were around the detection limit. The aim of this study was to investigate the
      ground water transport behavior of the pharmaceuticals clofibric acid,
      propyphenazone, and diclofenac with a laboratory soil column experiment. Results
      show that clofibric acid exhibits no degradation and almost no retardation (Rf =
      1.1). Diclofenac (Rf = 2.0) and propyphenazone (Rf = 1.6) are retarded, whereas
      significant degradation was not observed for both pharmaceuticals under the
      prevailing conditions in the soil column. We conclude that the concentration
      distribution of the pharmaceuticals at the bank filtration site at Lake Tegel is
      controlled by sorption, desorption, and input variation, rather than by
      degradation.

PMID- 15457800
TI  - A tracer dilution method for fracture characterization in bedrock wells.
AB  - This investigation was undertaken to develop an integrated method of downhole
      fracture characterization using a tracer. The method presented can be used to
      locate water-bearing fractures that intersect the well, to determine the ambient
      fracture flow rate and hydraulic head, and to calculate fracture transmissivity.
      The method was tested in two fractured crystalline bedrock wells located at the
      University of Connecticut in Storrs. The method entails injecting a tracer
      (uranine dye) into the well, while at the same time water is pumped out of the
      well. After steady-state conditions are reached, a borehole tracer concentration
      profile is developed. The dilution of the tracer is used to locate the inflowing
      fractures and to determine their flow rate. The fracture flow rate, plus the
      drawdown in the well, is then used to determine the fracture hydraulic head,
      transmissivity, and ambient flow rate.

PMID- 15457801
TI  - A simple approach using Bouwer and Rice's method for slug test data analysis.
AB  - Slug test data obtained from tests performed in an unconfined aquifer are
      commonly analyzed by graphical or numerical approaches to determine the aquifer
      parameters. This paper derives three fourth-degree polynomials to represent the
      relationship between Bouwer and Rice's coefficients and the ratio of the screen
      length to the radius of the gravel envelope. A numerical approach using the
      nonlinear least squares and Newton's method is used to determine hydraulic
      conductivity from the best fit of the slug test data. The method of nonlinear
      least squares minimizes the sum of the squares of the differences between the
      predicted and observed water levels inside the well. With the polynomials, the
      hydraulic conductivity can be obtained by simply solving the nonlinear least
      squares equation by Newton's method. A computer code, SLUGBR, was developed from
      the derived polynomials using the proposed numerical approach. The results of
      analyzing two slug test datasets show that SLUGBR can determine hydraulic
      conductivity with very good accuracy.

PMID- 15457802
TI  - "From models to performance assessment: the conceptualization problem," by John
      D. Bredehoft, September-October 2003 issue, v. 41, no. 5: 571-577.

PMID- 15457803
TI  - "A stream depletion field experiment," by Bruce Hunt, Julian Weir, and Bente
      Clausen, march-april 2001 issue, v. 39, no. 2: 283-289.

PMID- 15457804
TI  - Hydrogeology: A short history, Part 1.

PMID- 15457805
TI  - How learning one category influences the learning of another: intercategory
      generalization based on analogy and specific stimulus information.
AB  - We investigated the effect of learning one category structure on the learning of
      a related category structure. Photograph-name combinations, called identifiers,
      were associated with values of four demographic attributes. Two problems were
      related by analogous demographic attributes, common identifiers, or both to
      examine the impact of common identifier, related general characteristics, and the
      interaction of the two variables in mediating learning transfer from one category
      structure to another. Problems sharing the same identifier information prompted
      greater positive transfer than those not sharing the same identifier information.
      In contrast, analogous defining characteristics in the two problems did not
      facilitate transfer. We computed correlations between responses to first-problem
      stimuli and responses to analogous second-problem stimuli for each participant.
      The analogous characteristics produced a tendency to respond in the same way to
      corresponding stimuli in the two problems. The results support an alignment
      between category structures related by analogous defining characteristics, which
      is facilitated by specific identifier information shared by two category
      structures.

PMID- 15457806
TI  - Working memory components in written sentence generation.
AB  - College students wrote either simple or complex sentences using 2 prompt nouns
      while components of working memory were distracted with a concurrent task. Loads
      on the visual and spatial components of working memory (retain a shape) and
      verbal component (retain 3 or 6 digits) were compared with a no-load control.
      Only the 6-digit load reliably reduced sentence length relative to the control,
      suggesting that unimpeded sentence generation requires verbal working memory. The
      sentence length effect may arise from a failure to retrieve and maintain lexical
      representations during grammatical encoding. Memory load had no effect on
      grammatical and spelling errors, implying that syntactic and orthographic
      processing were undisturbed. Other possibilities locate the difficulty in
      planning conceptual content or in phonological encoding, but some evidence speaks
      against them.

PMID- 15457807
TI  - Disconfirmed hedonic expectations produce perceptual contrast, not assimilation.
AB  - In studies of hedonic ratings, contrast is the usual result when expectations
      about test stimuli are produced through the presentation of context stimuli,
      whereas assimilation is the usual result when expectations about test stimuli are
      produced through labeling, advertising, or the relaying of information to the
      subject about the test stimuli. Both procedures produce expectations that are
      subsequently violated, but the outcomes are different. The present studies
      demonstrate that both assimilation and contrast can occur even when expectations
      are produced by verbal labels and the degree of violation of the expectation is
      held constant. One factor determining whether assimilation or contrast occurs
      appears to be the certainty of the expectation. Expectations that convey
      certainty are produced by methods that lead to social influence on subjects'
      ratings, producing assimilation. When social influence is not a factor and
      subjects give judgments influenced only by the perceived hedonic value of the
      stimulus, contrast is the result.

PMID- 15457808
TI  - The distinctiveness of emotion concepts: a comparison between emotion, abstract,
      and concrete words.
AB  - Are the concepts represented by emotion words different from abstract words in
      memory? We examined the distinct characteristics of emotion concepts in 3
      separate experiments. The first demonstrated that emotion words are better
      recalled than both concrete and abstract words in a free recall task. In the
      second experiment, ratings of abstract, concrete, and emotion words were compared
      on concreteness, imageability, and context availability scales. Results revealed
      a difference between all 3 word types on each of the 3 scales. The third
      experiment investigated priming in a lexical decision task for homogeneous
      (abstract-abstract and emotion-emotion) and heterogeneous (abstract-emotion and
      emotion-abstract) associated word pairs. Priming occurred only for the
      homogeneous and heterogeneous abstract-emotion word pair conditions. Possible
      explanations for these findings are discussed in terms of the circumplex,
      hierarchical, and semantic activation models. The results are most consistent
      with the predictions of the semantic activation model.

PMID- 15457809
TI  - The role of gestures in spatial working memory and speech.
AB  - Co-speech gestures traditionally have been considered communicative, but they may
      also serve other functions. For example, hand-arm movements seem to facilitate
      both spatial working memory and speech production. It has been proposed that
      gestures facilitate speech indirectly by sustaining spatial representations in
      working memory. Alternatively, gestures may affect speech production directly by
      activating embodied semantic representations involved in lexical search.
      Consistent with the first hypothesis, we found participants gestured more when
      describing visual objects from memory and when describing objects that were
      difficult to remember and encode verbally. However, they also gestured when
      describing a visually accessible object, and gesture restriction produced
      dysfluent speech even when spatial memory was untaxed, suggesting that gestures
      can directly affect both spatial memory and lexical retrieval.

PMID- 15457810
TI  - Seeing a voice: Rudolph Koenig's instruments for studying vowel sounds.
AB  - The human voice was one of the more elusive acoustical phenomena to study in the
      19th century and therefore a crucial test of Hermann von Helmholtz's new theory
      of sound. This article describes the origins of instruments used to study vowel
      sounds: synthesizers for production, resonators for detection, and manometric
      flames for visual display. Instrument maker Rudolph Koenig played a leading role
      in transforming Helmholtz's ideas into apparatus. In particular, he was the first
      to make the human voice visible for research and teaching. Koenig's work reveals
      the rich context of science, craft traditions, experiment, demonstration culture,
      and commerce in his Paris workshop.

PMID- 15457811
TI  - Women and insomnia.
AB  - The occurrence of insomnia in women is influenced in great part by the complex
      hormonal cycles they undergo. Patterns of insomnia in younger women may be
      physiologically different on a hormonal basis from those found in older women.
      Although significant objective sleep disturbances have been difficult to
      demonstrate across the menstrual cycle in normal women, the International
      Classification of Sleep Disorders (ICSD) includes premenstrual insomnia and
      premenstrual hypersomnia as sleep disorders within the category of menstrual
      associated sleep disorder. On the other hand, during pregnancy and after
      childbirth, profound fluctuations in steroid and hypothalamic-pituitary-adrenal
      axis-related hormones produce significant physiological changes, including sleep
      disruption. During the menopausal transition, significant sleep disruptions are
      provoked by sleep-disordered breathing, vasomotor disturbance, and mood
      disorders. Regardless of age, women with chronic insomnia are at higher risk for
      developing or sustaining depression. Thoughtful management approaches must
      consider known relationships between menstrual or menopausal status and various
      sleep disorders, and should rely on pharmacologic, nonpharmacologic, or a
      combination of treatments to achieve successful relief from insomnia. The off
      label, first-line use of antidepressants for treating insomnia in the absence of
      depression is now considered debatable. The long-term efficacy and safety of the
      newer benzodiazepine receptor agonists (BZRAs) for insomnia, whether taken
      nightly or episodically, are supported by existing clinical experience. US Food
      and Drug Administration guidelines limiting the use of hypnotics to only a few
      weeks predate the newer generation BZRAs, and, as such, the guidelines may no
      longer be truly appropriate for these new agents.

PMID- 15457812
TI  - Depression and insomnia in women.
AB  - Depression and insomnia are both significantly more prevalent in women than in
      men. Risks appear linked to fluctuations and transitions in gonadal hormones
      during various phases of women's lives, with the risk of depression greatest
      during the period from menarche to menopause. Increased risks of both insomnia
      and depression also coincide with the late luteal phase of the menstrual cycle,
      during and after pregnancy, and during the peri-/postmenopausal period. Gonadal
      hormones exert significant effects on the neurohumoral systems most intimately
      associated with depression and insomnia, with corresponding implications for
      treatment. Medications related to the serotonin system-the selective serotonin
      reuptake inhibitors, or SSRIs-appear to be uniquely effective in the treatment of
      insomnia and depression experienced by women. SSRIs and the nonbenzodiazepine
      receptor agonists are generally useful as first-line treatments in a number of
      circumstances; hormone replacement therapies can also be considered. Behavioral
      therapies for insomnia may be particularly relevant for postpartum patients
      because of safety concerns and to prevent the development of autonomous chronic
      insomnia, which may also increase the risk of depression. In light of the high
      risk of relapse and high likelihood of comorbidity, it is crucial to effectively
      treat both insomnia and depression in women. However, few data exist for many key
      areas related to the treatment of these disorders in women, and research is
      greatly needed.

PMID- 15457813
TI  - A longitudinal study of changes in evoked otoacoustic emissions and pure-tone
      thresholds as measured in a hearing conservation program.
AB  - Non-linear transient-evoked otoacoustic emissions (TEOAEs) at 74dB pSPL,
      distortion-product otoacoustic emissions (DPOAEs) at 65/45dB SPL and pure-tone
      audiometry were used to detect noise-induced, inner car changes in a longitudinal
      study. Repeated-measures ANOVAs were made on the Noise (n=69) and Quiet (n=42)
      groups. The Noise group's hearing thresholds increased by 1.2 dB and DPOAE
      amplitude decreased by -0.9 dB. For both groups, TEOAE amplitude decreased by
      approximately -0.6 dB. Eight of 12 ears with permanent threshold shift (PTS) and
      10 of 13 ears with temporary threshold shift (TTS) showed TEOAE decrements or low
      baseline TEOAE amplitudes. Fewer TTS and PTS ears also showed DPOAE decrements,
      and there was never a DPOAE decrement without a corresponding TEOAE decrement or
      low TEOAE baseline. Some TTS ears showed permanent emission decrements. Although
      otoacoustic emissions show promise in detecting noise-induced inner ear changes,
      it is premature to use them in hearing conservation programs.

PMID- 15457814
TI  - Occupational hearing loss: screening with distortion-product otoacoustic
      emissions.
AB  - Hearing assessment of applicants for occupational hearing loss compensation can
      be a time-consuming process. An accurate screening procedure that is sensitive to
      occupational hearing loss may have application in many situations. The present
      study developed distortion-product otoacoustic emission (DPOAE) screening
      criteria to identify subjects likely to meet the Hong Kong requirements for
      occupational hearing loss compensation, namely a bilateral sensorineural loss >
      or = 40 dB HL (average of 1000, 2000 and 3000 Hz). The screening criteria of 1500
      and/or 2000 Hz, with a signal-to-noise ratio of > 0 or 3 dB, yielded high
      sensitivity and specificity. DPOAE measures therefore have the potential to
      accurately indicate possible occupational hearing loss. However, DPOAEs should be
      used as a screening tool only, as conventional puretone audiometry remains the
      more comprehensive measure of hearing sensitivity.

PMID- 15457815
TI  - Development of an auditory test battery for young children: a pilot study.
AB  - This article describes the development and results of a pilot study with a
      recently developed auditory test battery for 4-6-year-old Dutch children. The
      test battery consisted of a sustained auditory attention (SAA) test, a dichotic
      words (DW) test, a binaural masking-level difference (BMLD) test, an auditory
      word discrimination (AWD) test, a gap detection (GD) test and a test of phonemic
      awareness, the Lindamood Auditory Conceptualization (LAC) test. Our results show
      that this test battery can be administered successfully to children aged 4 years
      and older. Most tests showed a clear effect of chronological age; the strongest
      age effects were found for the DW test and the LAC test. The BMLD test was the
      only test for which no significant age effect was found in this group of
      children. A small, but significant right-ear advantage was found on the DW test,
      for the 4- and the 6-year-olds. Correlations between subtests were in general
      rather high, suggesting that several tests in this test battery may be tapping
      into similar auditory abilities.

PMID- 15457816
TI  - Near-threshold recordings of amplitude modulation following responses (AMFR) in
      children of different ages.
AB  - Amplitude modulation following responses (AMFR) to single near-threshold 40-Hz or
      80-Hz amplitude-modulated tones of 1 kHz were recorded in 48 normal children
      between the ages of 2 months and 14 years. Children under the age of 2 years were
      tested during natural sleep, and older children were tested awake. The objectives
      of this study were to find out how the AMFR changes with age and to determine the
      most effective modulation frequency for objective threshold assessment at
      different ages. The optimal modulation frequency changed from higher to lower
      modulation frequencies at about 13 years. In younger children, the 80-Hz AMFR was
      larger than the 40-Hz AMFR. The 40-Hz response became similar to the adult
      response by the age of 14 years, while the 80-Hz response had an amplitude
      greater than half of an adult response by the age of 1 year, changed very little
      during the investigated period, and reached the amplitude of adult responses at
      the end of the investigated period.

PMID- 15457817
TI  - Spatial spread of neural excitation: comparison of compound action potential and
      forward-masking data in cochlear implant recipients.
AB  - The feasibility of using the electrically evoked compound action potential
      (ECAP), measured with the NRT system (Neural Response Telemetry) and the NRT
      software (version 2.04), to quantify the longitudinal spread of neural excitation
      was examined in four subjects fitted with the Nucleus C124M cochlear implant. The
      ECAP and psychophysical forward-masking profiles were measured using stimulation
      on each of three electrodes, in basal, middle and apical positions. Spatial
      spread profiles derived from the ECAP measure produced broader functions than
      those derived from the psychophysical measure. These results, together with
      investigation of the change of ECAP spread pattern with stimulation current,
      suggest that functions derived from this 'simple' method were more influenced by
      the spread of electric field from excited neuron to electrode array than by
      breadth of the neural excitation pattern. The recently released NRT version 3.0
      permits the masker and probe pulses to be delivered to separate electrodes, thus
      removing a fundamental limitation of version 2.04. Results from a pilot study, in
      which this capability was exploited, suggest that the spatial functions from this
      'advanced' method may provide a better correlation with results from
      psychophysical forward masking.

PMID- 15457818
TI  - An investigation into the effect of limiting the frequency bandwidth of speech on
      speech recognition in adult cochlear implant users.
AB  - The purpose of this study was to investigate the effect of the limited-frequency
      bandwidth employed by telephones (300-3400Hz) on speech recognition in adult
      cochlear implant users. The Four Alternative Auditory Feature (FAAF) test was
      used in four conditions: unfiltered and in three filtered conditions of 300
      4500Hz, 300-3400Hz and 300-2500Hz. Ten subjects implanted with the Nucleus C124M
      device and 10 normal-hearing listeners were assessed to examine differences
      between word discrimination scores in each condition. Scores obtained from the
      300-3400-Hz and 300-2500-Hz filtered conditions were significantly worse than
      those with unfiltered speech for the cochlear implant subjects, decreasing by
      17.7% and 21.4%, respectively, from scores with unfiltered speech. By contrast,
      the normal-hearing listeners did not experience difficulties in discriminating
      between words in any of the conditions. Analysis of the word errors demonstrated
      that the reduction in implant subject scores with bandwidth arose from errors in
      place of articulation. Filtering speech in this way has a significant effect on
      speech recognition for cochlear implant subjects but not normal-hearing
      listeners. Hence, the limitations of the normal telephone bandwidth can be
      expected to have a negative effect on speech recognition for cochlear implant
      users using the telephone.

PMID- 15457819
TI  - Pitch estimation of a deeply inserted cochlear implant electrode.
AB  - In this short communication, we evaluate the place-pitch relation of a newly
      designed, deeply inserted, cochlear implant electrode. The insertion depths
      ranged from 471 degrees to 662 degrees. Pitch perception was measured in eight
      subjects with monopolar stimulation on each electrode contact at intensities of
      50% and 80% of the dynamic range. We observed a monotonic reduction of pitch
      estimate with insertion depth. For about half of the subjects, a flattening of
      the pitch estimate at the basal end of the electrode was seen, while for the
      other half, pitch continued to decrease monotonically up to the most apical part
      of the array. We conclude that deeper insertion could increase pitch range for at
      least some cochlear implant recipients, and could hence potentially increase
      group performance.

PMID- 15457820
TI  - [Spanking in early childhood makes a deep mark. American study shows a connection
      between behavior problems among school age children].

PMID- 15457821
TI  - [Occurrence of human papillomavirus is a positive factor in tonsillar cancer.
      Reduced risk of recurrence and longer survival].
AB  - The purpose of this article is to review the current knowledge on the status and
      significance of human papillomavirus (HPV) in tonsillar cancer. Current data
      demonstrate that approximately half of all tonsillar cancer is HPV positive.
      Moreover, patients with HPV positive cancer have a less risk of relapse and have
      a longer survival compared to patients with HPV negative tonsillar cancer. The
      longer survival is not dependent on that HPV positive tonsillar cancer is more
      sensitive to radiation therapy. However, in general HPV positive cancer exhibits
      less genetic instability in that it has a lesser degree of aneuploidy and fewer
      chromosomal aberrations when compared to HPV negative tonsillar cancer.

PMID- 15457822
TI  - [Perform more hysteroscopies! Safe and cost-efficient in intrauterine changes].

PMID- 15457823
TI  - [HIV in Sweden--more and more part of the world epidemic].
AB  - During the years 1997-2001 there were 1213 cases of HIV reported in Sweden. By
      using a questionnaire sent to respective clinics, additional information was
      obtained for 1018 patents. The transmission routes were: 28 per cent homosexual,
      65 per cent heterosexual, 10 per cent intravenous drug abuse, 1 per cent blood
      transfusion (none in Sweden) and 6 per cent other/unknown. 61 per cent of men
      infected by sex with men had contracted their infection in Sweden whilst this was
      true for 14 per cent of heterosexually infected men and 20 per cent of
      heterosexually infected women. Instead many with heterosexually transmitted
      infections had been infected in Africa or Asia where in many cases the patients
      also originated from. In 15 per cent of cases the HIV infection was detected in
      conjunction with a diagnosis of aids. Partner notification led to at least 0.12
      (127/1018) new cases per index case.

PMID- 15457824
TI  - [Analysis of the legislation concerning female genital surgery. Esthetic and
      sexual motifs are accepted--but not the traditional and religious ones].

PMID- 15457825
TI  - [Vulvar surgery--hazardous intervention, psychosexual aspects must be
      considered].

PMID- 15457826
TI  - [When is whistleblowing allowed? When is public reporting on unethical activities
      within own organization justified? Guidelines proposal].

PMID- 15457827
TI  - [Obesity in Lakartidningen through the times. Shrinking soldiers, apple-men and
      pear-women].

PMID- 15457828
TI  - [The campaign for TBE vaccination of small children is unethical and incorrect].

PMID- 15457829
TI  - [The greenhouse effect an issue for the medical profession].

PMID- 15457830
TI  - [Orthorexia nervosa--a new disease?].

PMID- 15457831
TI  - Nurses and their workplaces: necessary improvements.

PMID- 15457832
TI  - The report of the Task Force on the North Carolina Nursing Workforce--May 2004.
AB  - North Carolina is indeed fortunate to have avoided many of the extreme shortages
      of nurses reported in other states. Yet, even as this was noted, there were
      important developments on the horizon which had the potential to cause such
      shortages even here. The fact that there are so many pathways into this field and
      throughout an individual nurse's career made it necessary to organize our
      deliberations in a way that enabled the Task Force to deal with the special
      (often unique) situations faced by one form of nursing education, or one avenue
      of nursing practice. The Task Force then had to synthesize these findings and
      recommendations in a format that offered a potential framework for future policy
      decisions affecting the profession of nursing as a whole. It is a tribute to both
      the process and the participants that the way these discussions unfolded may have
      identified ways in which seemingly disjointed elements of North Carolina nursing
      might begin to see opportunities for collaboration, coordination, and ultimately
      greater levels of accomplishment in relation to the broad goals of this effort as
      a whole. In this report, as one would expect, there are identifiable needs: for
      additional financial support for nursing education (through support to our public
      and private institutions and their faculties offering different types of nursing
      credentials, as well as for the scholarship support of those who choose to enter
      this field), for programs and initiatives to enable recent nursing school
      graduates to enter nursing better prepared to render the professional services
      for which they were employed, and for concrete improvements in the nursing work
      environments. The fact that nursing, especially nursing at the bedside in
      hospitals and in long-term care, requires increasingly sophisticated technical
      skills and continues to demand intellectual, physical and emotional energy beyond
      what would be required in many other professions and occupations, the recruitment
      and retention of well-prepared and motivated nurses remains a challenge now and
      in the future. But, as these discussions and the interactions with Task Force
      members have demonstrated over and over again, nursing is both a dynamic and
      exciting field of professional practice. And North Carolina is considered by most
      to be one of the very best states within which to be a nurse. It is hoped that
      all the 47 recommendations offered in this report, only 16 of which are specified
      here, will serve as a template for a deliberate policy agenda through which the
      nursing workforce for North Carolina can continue to be the vibrant example of
      the highest standards of practice for which its reputation has been well-earned.

PMID- 15457833
TI  - Managing medical waste to protect public health and cut costs.

PMID- 15457834
TI  - The power of positive nursing.

PMID- 15457835
TI  - The policy crunch.

PMID- 15457836
TI  - The paradox of the not-for-profit hospital.
AB  - This quantitative research study assesses the organizational characteristics,
      market factors, and performance of not-for-profit hospitals in the United States.
      These results have managerial implications related to hospital efficiency,
      organizational performance, and the role of not-for-profit hospitals within local
      communities. The study has policy implications on access to clinical services
      within local communities, the availability of charity care, and the long-term
      viability of the not-for-profit health care industry due to potential bankruptcy
      and closure. This study clearly demonstrates that not-for-profit hospital
      managers are faced with declining profitability and are challenged to reduce
      hospital-operating expenses while meeting their charitable mission. Additionally,
      the greater size and increased clinical complexity of not-for-profit hospitals
      are increasing organizational overhead. In many cases, the increased clinical
      complexity is a commitment to the organizational mission of providing a full
      range of services to the community. From a policy perspective, the study suggests
      that not-for-profit hospitals have aging facilities and reduced cash flow due to
      lower profit margins. As a result, many not-for-profit hospitals face potential
      bankruptcy and closure. This study clearly documents a threat to the provision of
      charity care in local communities and the long-term viability of the not-for
      profit health care industry in the United States.

PMID- 15457837
TI  - Health care professionals as online faculty.
AB  - Online degrees in the health care professions are becoming more popular everyday.
      Teaching online is a convenient and flexible part-time job for health care
      professionals, but it is different than teaching in a classroom. As demand
      increases so will the opportunities for health care professionals to teach online
      courses from their home. What should part-time faculty expect when they teach
      online?

PMID- 15457838
TI  - Job satisfaction among hospice workers: what managers need to know.
AB  - The purpose of this study was to investigate the perception of job satisfaction
      among hospice interdisciplinary team members, which included social workers,
      nurses, spiritual care providers, and home health aides. Interdisciplinary team
      members (n = 72) from 4 hospice organizations in the Midwest participated in the
      study. Results of this study show that job satisfaction as defined by hospice
      workers includes having task significance, supervisory support, integration,
      distributive justice, positive affectivity, autonomy, routinization, no role
      overload, and high levels of work motivation. These same workers also stated that
      (1) working with patients and families and carrying out the hospice philosophy
      (task significance), (2) being comfortable with their level of knowledge and
      skills (competence), and (3) having good relationships with team members
      (integration) play a significant role in their degree of satisfaction on the job.
      These results have implications for managers in hospice organizations.
      Specifically, managers in health care organizations like hospices need to be
      apprised of what factors result in job satisfaction among employees.

PMID- 15457839
TI  - The practicality of employee empowerment: supporting a psychologically safe
      culture.
AB  - In times of workforce shortages and increasing pressures to compete, health care
      organizations need to advance and ameliorate their resources to ensure
      organizational success. Other industries have maximized empowerment initiatives
      as a strategy to retain and develop employees as primary stakeholders of its
      mission. While the notion of employee empowerment is by itself noble, for it to
      succeed, health care organizations must promote a culture of psychological safety
      to ensure a genuine commitment exists in its mission and strategies.

PMID- 15457840
TI  - Enhancing emotional intelligence in the health care environment: an exploratory
      study.
AB  - Emotional intelligence (EI), or knowledge of how emotions function in self and
      others, is a popular construct in both scientific and professional communities.
      Current theoretical models suggest that EI is a combination of dynamic skills
      that can be learned and enhanced through participation in targeted intervention
      programs. Although popular, few if any of the aforementioned interventions have
      been subjected to empirical scrutiny. Consistent with calls for efficacy studies
      of intervention programs, the purpose of this exploratory study was to examine
      the effect of an adventure-based intervention on the EI of employees of a
      multisite dental practice. Fifteen individuals completed the Mayer-Salovey-Caruso
      Emotional Intelligence Test before and after participation in a day-long
      intervention. Results suggest that the intervention had a small but positive
      effect on the participants' EI and that improvements in the 4 branches of EI
      varied within employee subgroups. Implications for future research and practical
      considerations for the health care environment are discussed.

PMID- 15457841
TI  - Hospitalists: Evolution, evidence, and eventualities.
AB  - Hospitalists are physicians who spend at least 25% of their professional time
      serving as the physicians-of-record for inpatients, during which time they accept
      "hand-offs" of hospitalized patients from primary care providers, returning the
      patients to their primary care providers at the time of hospital discharge. The
      hospitalist movement is only about 5 years old, yet at least 7000 hospitalists
      practice today and an estimated 19,000 will ultimately practice, approximately
      the current number of emergency medicine physicians. The emerging positivist
      literature on hospitalists' impact is the subject of this review. It traces the
      nature and evolution of the hospitalist movement; summarizes empirical evidence
      about costs, clinical outcomes, patient satisfaction, and education; and
      appraises whether the hospitalist model is indeed novel. The review concludes by
      outlining research questions about the hospitalist model's viability over time,
      the mechanisms by which it produces benefits, and especially hospitalists'
      longitudinal effect on continuity of patient care. A literature "scorecard" might
      rank evidence to date on costs as positive, evidence on clinical outcomes and
      education as nonnegative, and evidence on patient satisfaction and continuity of
      care as inconclusive. Above all, longitudinal research must illuminate whether
      hospitalists' advantages comeat the cost of the doctor-patient relationship.

PMID- 15457842
TI  - Strategic implications of culturally competent care.
AB  - Providing culturally competent care has implications for health care managers and
      their organizations that go beyond a simple clinical perspective. The article
      defines culturally competent care and suggests what the specific strategic
      implications of delivering such care are. The author suggests the definition of
      culturally competent care for a health care manager as "the ability of any health
      care provider of any cultural background in one's organization to effectively
      treat any patient of any cultural background." Four basic steps are suggested for
      an organization wishing to develop a program of delivering culturally competent
      care to include situation analysis, strategy formulation, strategy
      implementation, and strategic control.

PMID- 15457843
TI  - Creating a culture of service excellence: empowering nurses within the shared
      governance councilor model.
AB  - Through the shared governance council model, staff nurses at Delnor Community
      Hospital were empowered in an organization that encouraged professional autonomy
      over practice, effective communication, and development of leadership skills.
      Nursing strategic plans were carefully designed and specifically structured to
      lead to successful implementation of a shared governance model and a new nursing
      culture of excellence. The shared decision-making structure was the vehicle used
      to integrate the 14 standards of Magnet Nursing to create a culture of high
      quality nursing practice to achieve optimal outcomes. Nursing excellence was
      further verified by achieving outstanding results in patient, physician, and
      nurse satisfaction scores and nurse retention.

PMID- 15457844
TI  - Professional ethics at the bottom line.
AB  - Recently, there has been much written about professional ethics in health care,
      but the literature has tended to focus on the ethical care and treatment of
      patients and protection of their privacy and confidential information. This
      article focuses on the ethical behavior of health care professionals and how they
      treat each other in the workplace. Examples of unethical behavior are described
      ranging from subtle favoritism by managers and bullying to crossing the legal
      line. Two specific cases demonstrate serious situations where it was necessary
      for colleagues to "blow the whistle" even at the risk of their own careers.

PMID- 15457846
TI  - A manager asks: "She is never wrong--just ask her".

PMID- 15457845
TI  - Managing employee performance.
AB  - Performance management consists of significantly more than periodic evaluation of
      performance. It is the art and science of dealing with employees in a manner
      intended to positively influence their thinking and behavior to achieve a desired
      level of performance. It is essential for the manager to always model positive
      behavior concerning performance; what one does or says as a manager always has an
      influence on others. The kinds of employee behavior most likely encountered
      relative to performance management efforts stem from resistance to change and
      lack of complete understanding of what is expected. Employee participation must
      be elicited whenever possible for performance improvement; as far as the inner
      working details of a specific job are concerned, there is no one who knows the
      job better than the person who does it everyday. For each task to be done, an
      employee needs to know what output is expected, how this output will be measured,
      and what standards are applied in assessing the output. Managing employee
      performance requires ongoing contact with each employee, regular feedback, and
      whatever coaching, counseling, and training are necessary to bring an employee
      back on track when a problem appears. Sustaining efficient and effective employee
      performance requires the manager's ongoing attention and involvement.

PMID- 15457847
TI  - Placental site trophoblastic tumor: an overview.
AB  - OBJECTIVE: To analyze 15 consecutive cases of placental site trophoblastic tumor
      seen in a single reference institution for gestational trophoblastic disease, San
      Gerardo Hospital, Monza, Italy. STUDY DESIGN: Consecutive patients affected by
      placental site trophoblastic tumors were selected from our computerized database.
      RESULTS: There were 15 patients with placental site trophoblastic tumor, with a
      median age of 35 years. The antecedent pregnancy was a term one in 6 cases (40%),
      a miscarriage in 4 cases (27%), a termination in 2 cases (13%) and a molar
      abortion in 2 cases (13%). In 1 case the previous pregnancy was unrecognized. The
      median interval from the last pregnancy was 12 months, and the presenting symptom
      in 11 cases was vaginal bleeding, in 2 cases amenorrhea, in 1case a nephrotic
      syndrome and in 1 case, presenting with metastatic disease, hemoptysis. Six
      patients were treated using neoadjuvant chemotherapy with
      etoposide/methotrexate/actinomycin-etoposide/ vincristine (EMA-CO) followed in 5
      of 6 (83%) cases by hysterectomy. One patient had only medical treatment with EMA
      CO because of a strong desire for or childbearing and had a complete response;
      after 15 months she was free from disease. The last 9 patients underwent surgery
      as the first therapy. Among these patients 1 had presented with metastatic
      pulmonary disease and underwent chemotherapy, with complete disappearance of the
      pulmonary lesions. Two of these 9 patients had a relapse; the mirst patient had a
      pelvic and bladder relapse, and 14 months after multiple chemotherapy and
      surgery, she died. The second had a suburethral relapse 2 months after initial
      surgery; after chemotherapy and surgery she was well and free of disease.
      CONCLUSION: Our experience suggests that the role of chemotherapy may be
      reconsidered not only for metastatic disease but als of or uterine disease when
      choosing conservative management in young, fertile patients who desire
      childbearing. Chemotherapy may play an important role in avoiding relapse or
      early metastases even in patients who underwent hysterectomy as primary
      treatment.

PMID- 15457848
TI  - Predictors of quality of life among long-term survivors of gestational
      trophoblastic disease.
AB  - OBJECTIVE: To identify predictors of quality of life (QOL) among women diagnosed
      with gestational trophoblastic tumor (GTT) 5-10 years earlier. STUDY DESIGN:
      Utilizing a cross-sectional, descriptive design, 111 survivors completed a
      comprehensive QOL interview. RESULTS: Univariate analyses revealed that numerous
      psychosocial variables correlated highly with overall QOL. However, multivariate
      analysis indicated that the significant predictors of long-term QOL were cancer
      specific distress, social support, spiritual well-being, reproductive concerns,
      gynecologic pain and sexual functioning. These 6 variables accounted for 77% of
      the variance in the overall QOL score. Post hoc analyses demonstrated that each
      of the predictors had unique effects on the QOL score. CONCLUSION: The variables
      identified in this model can guide future research and clinical care to reduce
      short- and long-term burdens associated with GTT.

PMID- 15457849
TI  - Familial recurrent hydatidiform mole: a review.
AB  - This article reviews published data on familial recurrent hydatidiform mole with
      particular reference to the genetic basis of this condition, the likely outcome
      of subsequent pregnancies in affected women and the risk of persistent
      trophoblastic disease following molar pregnancies in these families. Familial
      recurrent hydatidiform mole is characterized by recurrent complete hydatidiform
      moles of biparental, rather than the more usual androgenetic, origin. Although
      the specific gene defect in these families has not been identified, genetic
      mapping has shown that in most families the gene responsible is located in a 1.1
      Mb region on chromosome 19q13.4. Mutations in this gene result in dysregulation
      of imprinting in the female germ line with abnormal development of both embryonic
      and extraembryonic tissue. Subsequent pregnancies in women diagnosed with this
      condition are likely to be complete hydatidiform moles. In 152 pregnancies in
      affected women, 113 (74%) were complete hydatidiform moles, 26 (17%) were
      miscarriages, 6 (4%) were partial hydatidiform moles, and 7 (5%) were normal
      pregnancies. Molar pregnancies in women with familial recurrent hydatidiform mole
      have a risk of progressing to persistent trophoblastic disease similar to that of
      androgenetic complete hydatidiform mole.

PMID- 15457850
TI  - What is the best regimen for low-risk gestational trophoblastic neoplasia? A
      review.
AB  - A review of published and unpublished material was performed using medical
      databases, bibliographies and personal contact with peer experts to determine the
      best treatment of low-risk gestational trophoblastic neoplasia (GTN). Thirty-nine
      studies contained the minimum information required for inclusion in this study.
      Additional reports were retrieved but could not be disaggregated with sufficient
      accuracy to obtain valid comparative information. Four general regimen types were
      identified: methotrexate with/without folinic acid rescue, actinomycin, etoposide
      and 5-fluorouracil. The studies were compared based on effectiveness, cost and
      patient preference. Effectiveness and toxicity data were abstracted from the 39
      studies. Intuitive assumptions about cost and preference were made to help
      differentiate the regimens. The following regimens were judged to be superior
      based on the data available: oral methotrexate, 100 mg/m2; infusional
      methotrexate; and pulse actinomycin. The small sample size of these 3 regimens
      limited the generalizability of the conclusions, but pulse actinomycin appeared
      to be the best choice given the data available. There is a paucity of level 1 and
      2 evidence on the best chemotherapeutic management of low-risk GTN. A biochemical
      or consensus-based clinical definition of persistent disease and a standardized
      scoring system should be developed and used by future authors. The dearth of
      prospective, randomized information on this disease makes determination of the
      best practice and the choice of a best regimen problematic.

PMID- 15457851
TI  - Analysis of a candidate gene associated with growth suppression of
      choriocarcinoma and differentiation of trophoblasts.
AB  - OBJECTIVE: To isolate a choriocarcinoma suppressor gene and analyze its structure
      and function. STUDY DESIGN: We constructed a polymerase chain reaction-based
      subtracted fragmentary cDNA library between normal placental villi and
      choriocarcinoma cell line CC1. A novel homeobox gene, designated NECC1 (not
      expressed in differ choriocarcinoma clone 1), is included in this library. We
      analyzed the structure and function of NECC1 with molecular biology. RESULTS:
      NECC1 comprises an open reading frame of 219 nucleotides encoding 73 amino acids
      and contains a homeodomain as a consensus motif. NECC1 is located on human
      chromosome 4q11-q12, and its expression is ubiquitous in the brain, placenta,
      lung, smooth muscle, uterus, bladder, kidney and spleen. Normal placental villi
      abundantly expressed NECC1, but all choriocarcinoma cell lines examined and most
      surgically removed choriocarcinoma tissue samples failed to express it. We
      transfected this gene into choriocarcinoma cell lines and observed remarkable
      alterations in cell morphology and suppression of in vivo tumorigenesis.
      Induction of chorionic somatomammotropin hormone 1 by NECC1 transfection
      suggested differentiation of choriocarcinoma cells to syncytiotrophoblast-like
      cells. CONCLUSION: Our results suggest that loss of NECC1 expression is involved
      in malignant conversion of placental trophoblasts.

PMID- 15457852
TI  - History of the International Society for the Study of Trophoblastic Disease.

PMID- 15457853
TI  - Immunohistochemistry for the imprinted gene product IPL/PHLDA2 for facilitating
      the differential diagnosis of complete hydatidiform mole.
AB  - OBJECTIVE: To determine if immunohistochemistry for PHLDA2 (also known as IPL and
      TSSC3), the product of a paternally imprinted, maternally expressed gene, can be
      used as a tool in the differential diagnosis of molar gestations. STUDY DESIGN:
      Twenty-five cases (15 complete moles, 5 partial moles and five hydropic
      abortions) were stained by immunohistochemistry for PHLDA2 and scored (without
      knowledge of the diagnosis) for positivity in the villous cytotrophoblast and
      then compared to adjacent sections stained by p57KIP2 immunohistochemistry.
      RESULTS: All partial moles and hydropic abortions were positive for PHLDA2 and
      p57KIP2. There was strong PHLDA2 staining of the cytoplasm in virtually all cells
      of the villous cytotrophoblast, while p57KIP2 was localized to the nucleus in a
      subset of those cells. All complete moles were negative for both markers in the
      villous cytotrophoblast. CONCLUSION: Immunohistochemistry for PHLDA2 serves as a
      practical and reliable diagnostic marker for the discrimination of complete mole
      from partial mole and hydropic abortion. Since the immunohistochemical diagnosis
      of complete mole is based on a negative result, absence of staining, the use of
      both markers (PHLDA2 and p57KIP2) together could increase the level of confidence
      when making this prognostically important distinction.

PMID- 15457854
TI  - The Japanese trophoblastic disease classification.
AB  - OBJECTIVE: To evaluate the clinical usefulness of the "diagnostic score"for the
      detection of choriocarcinoma in persistent gestational trophoblastic disease
      without histologic findings. STUDY DESIGN: We reviewed the clinical records of
      and histologic reports on all 809 patients with persistent gestational
      trophoblastic disease treated with surgery and chemotherapy in Japan. There were
      347 cases of choriocarcinoma and 462 cases of invasive mole with histologic
      confirmation. We retrospectively applied the diagnostic score to all the
      patients. RESULTS: The sensitivity of the score for choriocarcinoma (the true
      positive rate of the score for histologic diagnosis of choriocarcinoma) was
      91.4%. The specificity of the score (the true positive rate of the score for the
      histologic diagnosis of invasive mole) was 94.1%. The accuracy of the score was
      92.8%. CONCLUSION: The diagnostic score is a unique scoring system for
      differentiating choriocarcinoma clinically from persistent gestational
      trophoblastic disease without histologic findings and for selecting the most
      appropriate chemotherapy. Proper management in the early stages strongly
      influences the outcome of these diseases. The scoring system should be very
      useful for comparing the nearly true incidence and treatment results with
      choriocarcinoma between nations.

PMID- 15457855
TI  - Studying changes in the incidence, diagnosis and management of GTD: the South
      Korean model.
AB  - OBJECTIVE: To evaluate the changing epidemiologic picture and clinical
      characteristics of gestational trophoblastic disease (GTD) in South Korea over
      the past 5 decades. STUDY DESIGN: Patient data were collected from 37 hospitals
      nationwide, the Korean Research Institute of Trophoblastic Disease registry and
      CHA University Comprehensive Gynecologic Cancer Center from the years of 1970s
      through the year 2002. Demographic data, pretreatment evaluation, treatment
      modality, chemotherapeutic regimen and their results according to the clinical
      International Federation of Gynecology and Obstetrics classification and World
      Health Organization prognostic score were analyzed. Management of high-risk
      gestational trophoblastic tumor (GTT) was reviewed in depth. RESULTS: The
      nationwide incidence of hydatidiform mole and GTT dropped from 40.0 per 1,000
      deliveries and 5.0 per 1,000 deliveries, respectively, in the 1970s to 2.0 per
      1,000 deliveries and 0.5 per 1,000 deliveries, respectively, in the 1990s. The
      rate of decline was slower in 2000-2002. Significant changes were also noted in
      age distribution, interval between the preceding pregnancy and disease, gravidity
      and parity, and distribution of low- and high-risk groups of GTT. CONCLUSION: The
      dramatic improvement in GTD over the past 5 decades in South Korea can be
      attributed to the following factors: refinement in terminology and
      classification, advances in pretreatment evaluation, development of effective
      chemotherapeutic agents, application of multimodal treatment and novel
      chemoagents for high-risk GTT.

PMID- 15457856
TI  - Successful salvage of relapsed high-risk gestational trophoblastic neoplasia
      patients using a novel paclitaxel-containing doublet.
AB  - OBJECTIVE: To describe one institution's results with a novel 3-drug doublet,
      consisting of paclitaxel, etoposide and cisplatin, for salvage of relapsed high
      risk gestational trophoblastic neoplasia (GTN) patients. STUDY DESIGN: Analysis
      of treatment results with the doublet regimen in two patients with
      recurrent/persistent high-risk choriocarcinoma in the Division of Gynecologic
      Oncology, Toronto-Sunnybrook Regional Cancer Centre, University of Toronto. Both
      patients had been treated previously with one or more of the doublet drugs.
      RESULTS: Both patients experienced complete responses, patient 1 for 13 months
      and patient 2 for 9. Patient 1 required surgical resection of a single focus of
      recurrence and was again in complete remission 27 months after completing her
      last course of doublet chemotherapy. Patient 2 has not relapsed since completing
      the treatment. CONCLUSION: The doublet regimen appears capable of producing a
      sustained response in patients with recurrent high-risk GTN who have previously
      undergone extensive chemotherapy. Further, the regimen seems to be reasonably
      well tolerated.

PMID- 15457857
TI  - Choosing abdominal incision and closure techniques: a review.
AB  - This review summarizes contemporary concepts of abdominal surgical incision
      creation and closure. The Ovid computerized database was searched for articles
      published in English from 1996 to 2003 using keywords pertaining to the specific
      topic of interest (e.g., suture, drain, surgical technique, fascia). Human
      prospective, randomized trials; meta-analyses; and evidence-based-focused reviews
      were assessed and data abstracted. Several earlier and animal-based studies on
      specific issues were included. The data indicate that: (1) the direction of the
      incision should be based upon obtaining adequate exposure; (2) hair should either
      be left in place or clipped at the time of surgery; (3) a single dose of
      prophylactic antibiotics should be given 30 minutes prior to surgery; (4) using a
      "deep" scalpel is unnecessary; (5) a scalpel and electrocautery are comparable
      for deepening the incision; (6) minimal peritoneal lavage with non-antibiotic
      containing solutions is adequate; (7) the peritoneum should not be routinely
      closed; (8) the fascia should be loosely approximated by a continuous mass
      closure using a slowly absorbable, monofilament suture with the smallest possible
      caliber and a suture:wound length ratio of at least 4:1; (9) retention sutures,
      subcutaenous sutures and drains do not appear to reduce the risk of wound
      complications; and (10) the skin may be closed in a variety of methods, but a
      semiocclusive dressing should be applied. As scientific evidence accumulates to
      refute traditional dogma, management of the surgical patient has undergone
      substantial changes. Surgeons should now be able to create and close an abdominal
      wound based upon sound scientific principles rather than simply "doing what I
      always do."

PMID- 15457858
TI  - Enhanced immunocompetent cells in chlamydial cervicitis.
AB  - OBJECTIVE: To investigate changes in cell-mediated immunophenotypes by flow
      cytometry in endocervical secretions and peripheral blood in women with Chlamydia
      trachomatis infection. STUDY DESIGN: Fifty women attending the gynaecology
      outpatient department of Safdarjang Hospital, New Delhi, India, with signs and
      symptoms of cervicitis were enrolled. All patients underwent endocervical
      screening for C trachomatis (direct fluorescence antibody test [DFA]), and any
      coinfection with Candida (Gram stain), bacterial vaginosis (Gram stain),
      Neisseria gonorrhoeae (Gram stain), Trichomonas vaginalis (wet mount) and HIV
      (enzyme-linked immunosorbent assay) was ruled out. Flow cytometry was done to
      investigate changes in immunophenotypes in endocervical secretions and peripheral
      blood using monoclonal antibodies for surface markers (CD3, CD4, CD8, CD19, CD45
      and CD83). Data were analyzed by chi2 test, while means were compared using
      Student's t test. RESULTS: C trachomatis positivity was found to be 36% (n = 18).
      Forty-eight patients constituted the study population since 2 patients coinfected
      with Candida, bacterial vaginosis and T vaginalis were excluded. A statistically
      significant enhancement in CD4+, CD8+ and dendritic cellular phenotypes was
      observed in the endocervical secretions of Chlamydia-positive patients, while B
      cells showed no marked difference. In the parallel study of matched peripheral
      blood, immunophenotypes did not show statistically significant results.
      CONCLUSION: Increased influx of CD4+, CD8+ and dendritic cells in the endocervix
      is an indication of cell-mediated immunity in response to C trachomatis
      infection. Local immune response in the cervical region is independent of
      systemic response. The mechanism by which local mucosal and systemic immune cells
      interact to repel or enhance susceptibility to C trachomatis infection requires
      further study.

PMID- 15457859
TI  - Increased tumor necrosis factor-alpha in whole blood during the luteal phase of
      ovulatory cycles.
AB  - OBJECTIVE: To evaluate whether the fact that blood from premenopausal, ovulatory
      women shows a significant fluctuation in tumor necrosis factor-alpha (TNF-alpha)
      levels when tested randomly over time is related to the hormonal cycle. STUDY
      DESIGN: In this pilot study, whole blood was collected from 8 women during the
      follicular, ovulatory and midluteal phases of the menstrual cycle. Ovulation was
      confirmed by luteinizing hormone surge and mid-luteal progesterone levels. For
      each subject at each phase of the menstrual cycle, TNF-alpha levels were measured
      at baseline and after stimulation of whole blood with 10 microg/mL of
      lipopolysaccharide (LPS). Supernatant was collected and assayed by enzyme-linked
      immunosorbent assay. TNF-alpha levels were compared with the Wilcoxon matched
      pairs signed rank sum test. RESULTS: Whole blood unstimulated by LPS showed
      increasing TNF-alpha levels over the hormonal cycle, with significantly increased
      median levels during the luteal phase (903 pg/mL; range, 0-3707) as compared with
      the follicular phase (162 pg/mL; range, 0-656) (P = .03). Blood stimulated with
      LPS showed increased TNF-alpha levels overall but no association with cycle
      timing. CONCLUSION: TNF-alpha levels in unstimulated whole blood appear to be
      associated with menstrual cycle timing, with highest levels during the luteal
      phase. However, the lack of variation in TNF-alpha production after LPS
      stimulation suggests that experiments do not need to be timed with the menstrual
      cycle.

PMID- 15457860
TI  - Triplet pregnancies in women aged 40 or older: a matched control study.
AB  - OBJECTIVE: To determine, in triplet pregnancies, if maternal age is associated
      with adverse outcome in terms of birth weight characteristics. STUDY DESIGN: We
      analyzed a nationwide cohort of live-born triplets compiled by Matria Healthcare
      (Marietta, Georgia). We compared all 171 mothers > or = 40 years old with
      randomly selected and matched-for-parity mothers aged 25-29 and 35-39 years. The
      main outcome measures were length of gestation and individual and total triplet
      birth weight. All the subjects had private health insurance. The sample size was
      adequate to detect 5% differences at a power of 80%. RESULTS: Birth weights for
      infants A, B and C were significantly higherfor mothers > or = 40 years (P =
      .016, .01, and .03, respectively); total triplet birth weight was significantly
      higher as compared with that in the younger controls (P =.01). Gestational ages
      were similar in the 3 groups. In addition, the frequencies of births at < 28
      weeks and of < 1,000 g were reduced by one-third or more in women aged 40 or
      older as compared to the younger controls (2.3% vs. 6.4% and 4.5% vs. 7.0%,
      respectively). CONCLUSION: Older mothers of triplets have better outcomes than do
      their younger counterparts in terms of total triplet birth weight.

PMID- 15457861
TI  - Intramural molar pregnancy: a case report.
AB  - BACKGROUND: Intramural pregnancy is a rare but potentially life-threatening
      condition. The condition remains unknown to many clinicians and sonographers.
      With the ever-increasing use of high-resolution ultrasound scanning, early
      diagnosis of the condition is now possible, provided that the condition is
      thought of. To our knowledge, this is the first reported case of intramural
      pregnancy treated with suction evacuation under laparoscopic guidance. CASE: A 28
      year-old woman presented with history of vaginal bleeding early in her fourth
      pregnancy, having had 2 previous suction terminations of pregnancy and evacuation
      of retained products of conception for incomplete miscarriage at 8 weeks'
      gestation 2 months earlier. An ultrasound scan showed a complex mass in the left
      fundal region of the uterus, and the serum beta-human chorionic gonadotropin
      levels were grossly elevated. The patient was found to have an intramural
      hyperplastic pregnancy, treated with suction evacuation under laparoscopic
      guidance and systemic methotrexate therapy. CONCLUSION: A macroscopic ostium led
      into the uterine cavity and made guided suction evacuation of the uterus
      possible. Early diagnosis can prevent a life-threatening situation and conserve
      reproductive function.

PMID- 15457862
TI  - Persistent tubal pregnancy presenting with delayed hemorrhage from a second
      implantation of trophoblast on the ovary: a case report.
AB  - BACKGROUND: The use of conservative surgical techniques to treat ectopic
      pregnancies has been reported to increase the rate of incomplete trophoblastic
      tissue removal and subsequent regrowth. CASE: A persistent ectopic pregnancy
      occurred in a woman previously treated with laparoscopic linear salpingostomy for
      an ampullary ectopic pregnancy. Repeat laparoscopy was performed, and bleeding
      from an ovarian implantation site was treated with resection of the trophoblastic
      site and electrocautery. A repeat linear salpingostomy was also performed at the
      site of the prior salpingostomy, where trophoblastic tissue also persisted.
      CONCLUSION: This is the first known case of hemorrhage from the probable
      secondary ovarian implantation of persistent trophoblastic tissue. A repeat
      conservative surgical procedure to treat persistent ectopic pregnancies and
      maintain potential fertility is advocated. This case also serves as a reminder to
      diligently examine all areas of the pelvis for the possible secondary
      implantation of persistent trophoblastic tissue should reoperation be necessary.

PMID- 15457863
TI  - Vesicovaginal fistula after Irving sterilization: a case report.
AB  - BACKGROUND: Patients scheduled for gynecologic surgery must be informed about the
      development of urogenital fistulae as a possible complication. CASE: A 49-year
      old woman underwent Irving sterilization with subsequent abdominal hysterectomy
      due to intraabdominal abscess formation. Inadvertent damage complication to the
      bladder during hysterectomy led to development of a vesicovaginal fistula despite
      intraoperative management. The fistula was repaired at once in a second session.
      As a sequela of bladder injury, the patient had recurrent vesical diverticula and
      urolithiasis with repeated removal of the diverticula and stones. A subsequent
      intervention performed laparoscopically led to development of a second
      vesicovaginal fistula. In addition, an anesthesia-induced complication resulted
      in cerebral hypoxia with postoperative development of Parkinson's disease.
      CONCLUSION: Retrospectively, there is doubt whether the proper surgical
      procedures were employed in this case. The fact that the patient had type 1
      diabetes mellitus gives rise to the question of why no conservative method of
      contraception was chosen. The type of operative approach in elective surgery
      should always be planned on the basis of the individual patient's overall
      condition and in relation to the anatomic situation.

PMID- 15457865
TI  - From rhetoric to reality.

PMID- 15457864
TI  - Incidence of vaginitis with the etonogestrel/ethinyl estradiol vaginal ring.

PMID- 15457866
TI  - Valuing diversity and reshaping power to create conditions for equity and health.

PMID- 15457867
TI  - More effective action for equity in health: strengthening the IUHPE's hand.

PMID- 15457868
TI  - Adolescents' perception of their own risk-taking behaviour.

PMID- 15457869
TI  - An analysis of the main educational factors influencing the implementation of
      health promoting schools in Hong Kong.

PMID- 15457870
TI  - A study about effectiveness of the health promoting schools network in Portugal.

PMID- 15457871
TI  - The Syrian Center for Tobacco Studies: a model of international partnership for
      the creation of sustainable research capacity in developing countries.

PMID- 15457872
TI  - World No Tobacco Day 2004: tobacco control and poverty in the European Union.

PMID- 15457873
TI  - Buried treasure: unlocking the riches in healthcare's data files requires
      computing that interprets language.

PMID- 15457874
TI  - PACS in the OR: surgeons, and the surgery suite, have special requirements for
      viewing digital images.

PMID- 15457875
TI  - ASTM E31 Committee: recent activities address CCR, transcription and
      documentation, and security and privacy.

PMID- 15457876
TI  - DICOM additions and advances: the standards committee works to keep up with
      technology.

PMID- 15457877
TI  - HL7 makes headway on Version 3: framers of the EHR draft standards invite the
      industry to try them out.

PMID- 15457878
TI  - ISO reference technology model: nursing diagnosis and action models look to
      testing for practical application.

PMID- 15457879
TI  - LOINC links grow: more and more groups are finding content in the database that
      they can use.

PMID- 15457880
TI  - SNOMED CT milestones: endorsements are added to already-impressive standards
      credentials.

PMID- 15457881
TI  - WEDI workings: tasked with advising HHS, the group develops consensus and
      recommendations on standards implementation.

PMID- 15457883
TI  - Emergency automation: staff report plenty of reasons to implement a clinical
      information system in the ED.

PMID- 15457882
TI  - Changing the course of healthcare: evidence-based medicine can bring benefits
      downstream.

PMID- 15457884
TI  - The last punch out. A finger-scanning system tracks employees' ins and outs, plus
      frees up payroll staff.

PMID- 15457885
TI  - A process for change: the vision of quality in healthcare includes technology as
      an important partner.

PMID- 15457886
TI  - Licensed to drive: organizations can save on licensing fees by knowing what they
      have and what they need.

PMID- 15457887
TI  - The hospital of tomorrow. Service providers are working on creative ways to
      improve communication.

PMID- 15457888
TI  - Specialty pharmacy presents unique set of challenges.

PMID- 15457889
TI  - We don't serve your kind!

PMID- 15457890
TI  - 'Healthy Mae' just might be Frist's biggest legacy.

PMID- 15457891
TI  - Medicaid fees rise, but still below Medicare.

PMID- 15457892
TI  - Spend money on healthy people!

PMID- 15457893
TI  - Bad tiered formulary designs yield poor outcomes, high cost.

PMID- 15457894
TI  - Preparing for NCQA: what not to do.

PMID- 15457895
TI  - Navigating the personnel rapids. What they never taught you in med school.

PMID- 15457896
TI  - State mandates promote contraceptive coverage.

PMID- 15457897
TI  - Free database encourages wide sharing of information on programs' outcomes.

PMID- 15457898
TI  - Employers take the lead in drug benefit design.

PMID- 15457899
TI  - 10,000 cells on a chip signal start of new era of diagnosis.

PMID- 15457900
TI  - Medical debt found to hinder access.

PMID- 15457901
TI  - Thoughts on a scary visit from an old acquaintance.

PMID- 15457902
TI  - Iowa Healthcare Collaborative tackles patient safety issues.

PMID- 15457903
TI  - Physician class action settlements--precursors of positive change.

PMID- 15457904
TI  - Another busy summer at IMS.

PMID- 15457905
TI  - Should you treat your own employees?

PMID- 15457906
TI  - The decision decade.

PMID- 15457907
TI  - The changing nature of death--what you need to know about OOH DNRs.

PMID- 15457908
TI  - Reappraising prosthodontic treatment goals for older, partially dentate people:
      Part II. Case for a sustainable dentition?
AB  - The second of this two-part series, on the theme of estimating prosthodontic
      treatment needs and goals for older, partially dentate people, examines the roles
      of patient-perceived functional impairment, treatment outcome and changing
      demographic profiles in influencing these goals. In contradistinction with the
      lack of compelling evidence for the basis of the traditional, morphologically
      driven prosthodontic treatment strategy, the evidence that the assessment of
      treatment need should take greater account of individuals' felt oral functional
      concerns, and thereby assuming a more problem-oriented, outcomes-based approach
      to prosthodontic decision-making, is gaining strength. Furthermore, the current
      blueprint guiding prosthodontic planning and procedures cannot be exempt from the
      far-reaching changes in society brought about by new economic and social
      realities, and will need to transform itself in the light of new evidence. How
      these realities translate in a developing country context is not certain, but it
      is known that inequalities in access to, and the provision of healthcare are
      related to socio-economic factors, be they prevailing or of residual nature from
      past structural conditions. Such conditions adversely affect peoples' health
      status and add urgency to the pursuit of viable and appropriate management
      strategies. In the context of a reappraisal of current prosthodontic paradigms,
      the shortened dental arch concept is presented as a potentially compelling
      strategy for the appropriate management of the ageing, partially dentate patients
      in South Africa, whose access to healthcare is inequitable. Since dental and oral
      health status is variable, the management strategy highlighted here should be
      seen as one, albeit an important one, within a range of available options.

PMID- 15457909
TI  - Caries status and treatment needs in South Africa: report of the 1999-2002
      National Children's Oral Health Survey.
AB  - A third national children's oral health survey was conducted in South Africa
      between July 1999 and June 2002. OBJECTIVE AND METHODOLOGY: One of the objectives
      of the survey was to determine the prevalence and severity of dental caries and
      the treatment needs for dental caries in 4- to 5-, 6-, 12- and 15-year-old South
      African school children. The sample comprised 30876 children from the nine
      provinces of South Africa. RESULTS: The results of the survey show that 39.7 per
      cent of the 6-year-old group were caries free. This figure, 39.7 per cent, is
      below the goal of 50 per cent set by the Department of Health for 6-year-old
      children in South Africa for the year 2000. The DMFT of 1.1 for the 12-year-old
      group on the other hand was below the goal of 1.5 set for South Africa for the
      year 2000. The highest DMFT/dmft scores were recorded in the Western Cape
      Province and the lowest in the Limpopo Province. More than 80 per cent of caries
      in children go untreated while the greatest need for treatment in South African
      school children was for preventive services, restorations and extractions. The
      results for the 12-year-old-group show a reduction in dental caries severity in
      the permanent dentition in that the DMFT decreased from 2.5 in 1982 to 1.1 for
      the current survey. CONCLUSIONS: Although dental caries severity in South Africa
      is classified as low by WHO standards, the high levels of untreated caries in all
      age groups in South Africa is a cause for concern.

PMID- 15457910
TI  - Oral health knowledge and original practices of African traditional healers in
      Zonkizizwe and Dube, South Africa.
AB  - Self reported oral health knowledge and practices of 83 traditional healers in
      Zonkizizwe (56) and Dube (27) Gauteng Province, South Africa were carried out
      using a questionnaire and clinical photographs of common oral conditions. The
      mean age for the total group was 49.5 with 35 males and 48 females. Although only
      17 of the healers were members of a professional association, many indicated
      their willingness to join one. 40 (71%) of healers in Zonkizizwe kept written
      client records but far fewer 3 (11%) did so in Dube. More than 90% of traditional
      healers from both areas correctly identified photographs of gingival
      inflammation, dental caries and oral candidiasis. Over 50% of healers from both
      areas had patients who presented with mouth problems. Ninety percent of healers
      in Zonkizizwe referred patients to the formal health care sector but less than
      50% in Dube did so. A vast majority of healers gave oral health advice to their
      patients, many of whom gave specific tooth brush instruction. The study provides
      an initial understanding of the practices of healers regarding oral health.

PMID- 15457911
TI  - The use of essential oil mouthwashes as preprocedural rinses for infection
      control.

PMID- 15457912
TI  - General practitioner's radiology case 23. Periapical cemental dysplasia.

PMID- 15457913
TI  - The "body of knowledge" in healthcare security.
AB  - The three basic elements of the "Body of Knowledge" that exists today in
      healthcare security--industry standard practices, best practices, and a standard
      of care--are defined and described for the healthcare practitioner who seeks to
      act in a professional manner.

PMID- 15457914
TI  - Measuring perception as a component of a security assessment.
AB  - Although there are many excellent ways available to conduct a security assessment
      of a hospital, measurement of the perception of security--a key ingredient in any
      security plan--is often lacking. In this article, the author describes and
      illustrates a survey instrument for measuring perception of security.

PMID- 15457915
TI  - A vision, goals and objectives statement for the 21st century.
AB  - The need to spell out the philosophy and goals of a hospital security department
      is set forth by the author, who outlines the Vision, Goals and Objectives
      statements used at two medical centers.

PMID- 15457916
TI  - "Everything always happens for the best: if you view it that way".
AB  - A candid and detailed description of the author's heart attack and its aftermath
      with advice to his colleagues on how to become more proactive in identifying and
      dealing with the risk factors associated with coronary heart disease.

PMID- 15457917
TI  - How has hospital security changed since 9/11?
AB  - The new expectations of healthcare institutions, including changes in security,
      response to catastrophic occurrences and the need to conduct community-wide
      drills is spelled out by the authors.

PMID- 15457918
TI  - Emergency preparedness: online resources for hospital healthcare and security
      professionals.
AB  - This article provides a list of web-based resources to assist hospital healthcare
      and security personnel in locating disaster recovery emergency response related
      information.

PMID- 15457919
TI  - Bio-terrorism, "dirty bombs," hospitals, and security issues.
AB  - In the event of a bio-terrorism event, the role of the hospital security
      department will be critical if the disaster plans of health care providers are to
      be successfully carried out. It is imperative, says the author, that security
      providers be involved in every step of disaster and emergency response planning.

PMID- 15457920
TI  - The dangers of home health.
AB  - Home health nurses can encounter dangerous situations in the field that are not
      faced in a hospital setting. This article describes a joint program by a medical
      center's security and home health departments to train and safeguard home health
      providers.

PMID- 15457921
TI  - Customer service and today's hospital security professional.
AB  - Customer service, benchmarking, and budget control have supplanted enforcement as
      the essential parts of hospital security operations, according to the author. In
      the article he emphasizes and illustrates the need for security satisfaction
      surveys and benchmarking to enable the budget process to go smoothly.

PMID- 15457922
TI  - Workplace violence: a new challenge.
AB  - While it may not be possible to predict employee violence, you can take steps to
      prevent it from happening at your facility.

PMID- 15457923
TI  - Parking garage threats and countermeasures.
AB  - Preventing and dealing with crime in hospital parking facilities poses a serious
      challenge to administration and security. Multiple methods to effectively combat
      the threats are described by the author, but their implementation depends on how
      seriously a healthcare organization views its responsibility to provide a safe
      and secure environment for its staff, patients and visitors.

PMID- 15457924
TI  - Natural disasters: responding to the unexpected.
AB  - No matter how well-prepared a hospital is for emergencies, when one does occur it
      invariably poses problems that were unforeseen. In this article, hospital
      security officials evaluate their response to two major disasters that occurred
      within two months of each other--the Oklahoma ice storm and the Seattle/Olympia
      earthquake.

PMID- 15457925
TI  - Effect of leptin on renal ischemia-reperfusion damage in rats.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been established as an important
      mediator in renal ischemia-reperfusion (I/R) injury. Leptin, a product of the ob
      gene, has been known to exhibit cytoprotective effects on renal tissue, but its
      effect on renal tissue TNF-alpha level after renal I/R injury in rats remains
      unknown. The purpose of the study was to evaluate the effects of leptin on renal
      tissue TNF-alpha, malondialdehyde (MDA), protein carbonyls (PCs) and total
      sulfydryl group (SH) levels, and plasma nitrite levels after renal I/R injury in
      rats. The animals were divided into three groups: control, I/R and I/R+leptin.
      Rats were subjected to renal ischemia by clamping the left pedicle for 45 min,
      and then reperfused for 1 h. The I/R+leptin group was pretreated
      intraperitoneally with leptin (10 microg/kg) 30 min before the induction of
      ischemia. Our results indicate that MDA, TNF-alpha levels, and PCs were
      significantly higher in the I/R group than those in the control group (p < 0.05).
      The administration of leptin decreased these parameters (p < 0.05) significantly.
      The SH level was observed to significantly decrease after I/R injury when
      compared to the control group (p < 0.05). Leptin treatment significantly
      increased tissue SH and plasma nitrite levels when compared to the I/R group (p <
      0.05). Plasma nitrite levels did not change significantly in I/R when compared to
      the control. These results suggest that leptin could exert a protective effect on
      I/R induced renal damage by decreasing TNF-alpha levels and increasing nitrite
      level.

PMID- 15457926
TI  - Daily ingestion of fermented milk containing Lactobacillus casei DN114001
      improves innate-defense capacity in healthy middle-aged people.
AB  - Different lactic acid bacteria have often been administered as a dietary means to
      enhance immune system activity. Based on this statement, the aim of the current
      work was to test the effects of a Lactobacillus casei DN114001 fermented milk
      consumption on the immune response capacity in middle-age volunteers. Forty-five
      healthy volunteers, 24 women and 21 men (aged: 51-58 years), were randomized into
      two groups to receive three cups per day of a L. casei DN114001 (10(8)-10(10)
      ufc/g) fermented milk (n = 23), or placebo (n = 22), during an 8-week period.
      Measurements were performed before (day 0), and after the nutritional
      intervention (day 56). After the trial, no changes in immune cell proportions
      were detected, but the probiotic-treated group increased oxidative burst capacity
      of monocytes (probiotic group: p = 0.029; placebo group: p = 0.625), as well as
      NK cells tumoricidal activity (probiotic group: p = 0.023; placebo group: p =
      0.125). Results showed that daily intake of fermented milk containing
      Lactobacillus casei DN114001 could have a positive effect in modulating the
      innate immune defense in healthy-middle-age people.

PMID- 15457927
TI  - Leptin effect on intestinal galactose absorption in ob/ob and db/db mice.
AB  - Our previous works demonstrated that leptin inhibits galactose absorption in rat
      and mice intestinal rings. Here, we have studied the effect of exogenous leptin
      on intestinal galactose absorption in the genetically obese db/db (leptin
      resistant) and ob/ob (leptin-deficient) mice. Assays were performed by incubating
      the intestinal rings in saline solution containing 5 mM galactose in the absence
      or presence of 0.2 or 0.4 nM leptin. Basal galactose uptake was similar in the
      wild-type and the two obese groups. Contrarily to what happens in wild-type mice,
      leptin increased galactose uptake in db/db animals; since these mice lack the
      functional long leptin receptor, the measured effect may be due to the short
      receptor signaling. In the ob/ob mice, 0.2 nM leptin also increased galactose
      absorption whereas 0.4 nM did not have any effect, suggesting that in the
      genetically obese animals the expression and regulation of leptin receptors may
      be altered.

PMID- 15457929
TI  - Inaugural address.

PMID- 15457930
TI  - Jump start your impressions. Tips for improving the impression-taking process.

PMID- 15457931
TI  - Diabetes and periodontal health.

PMID- 15457928
TI  - Role of histamine and platelet-activating factor in allergic rhinitis.
AB  - This review is focused on the effects of histamine and platelet-activating factor
      (PAF) in allergic rhinitis and the plausible implications for therapy. Rhinitis
      is defined as a heterogeneous disorder resulting from an IgE-mediated reaction
      associated with nasal inflammation of variable intensity. Two phases of response
      are triggered by an IgE/allergen cross-linking event: the first is the release of
      preformed mediators such as histamine or interleukins from mast cells and
      basophils; the second begins when cells start producing lipid-derived mediators.
      One of these mediators is PAF. Apart from leukotrienes, PAF is perhaps the most
      potent inflammatory mediator in allergic rhinitis for inducing vascular leakage,
      a response that may contribute to the appearance of rhinorrhea and nasal
      congestion.

PMID- 15457932
TI  - Unsure about the uninsured. With the nation's uninsured population up another
      3.2%, politicians spin the news, while hospitals wait for solutions.
AB  - As the latest statistics surfaced showing the uninsured population has hit 45
      million, politicians added spin and healthcare providers were still hoping for
      some solutions. Census official Daniel Weinberg, left, said the data don't reveal
      what caused a drop in employer-sponsored coverage.

PMID- 15457933
TI  - Even-steven: Calif. bill would limit hospital charges.

PMID- 15457934
TI  - Preparing for the worst: GPOs fear fallout from senate hearings.

PMID- 15457935
TI  - Indefinite delay: AHA wins support to extend moratorium.

PMID- 15457936
TI  - A matter of geography: GNYHA to fight HHSs' wage-index areas.

PMID- 15457937
TI  - Strike over benefits: employees stage walkout against group health.

PMID- 15457938
TI  - Singing the access blues: since Bush, Kerry offer no big solutions, maybe some
      modest ones are in order.

PMID- 15457939
TI  - The forgotten illness. Stigma still keeping many Americans from crucial mental
      health treatment.

PMID- 15457940
TI  - They're waiting impatiently. Despite rising demand, behavioral-health services
      still face lack of hospital capacity, stretched funding sources.

PMID- 15457941
TI  - A Texas-sized building boom. Healthcare systems are spending billions to meet
      surging demand with bigger, better facilities in flourishing Dallas-Fort Worth
      area.

PMID- 15457942
TI  - 'Top gun' for doc managers.

PMID- 15457943
TI  - [Conservative surgery--a basic principle of childhood urology].
AB  - Dysfunction of the solitary kidney was established in 58 patients after the
      contralateral kidney removal in childhood. The tests were made at senior school
      age, at adolescence, at adult age. The disorders in the renal function were more
      severe in pathological processes in the solitary kidney: chronic pyelonephritis,
      nephron dysplasia, etc. In 49 children the kidney was preserved even in
      functional failure 70-90%. These patients had less evident renal failure. Basing
      on this evidence and other arguments, the authors recommend to limit indications
      for nephrectomy in children.

PMID- 15457944
TI  - [Application of principles of evidence-based medicine in cancer of the urinary
      bladder].
AB  - Meta-analysis has been made to answer the question whether a proven advantage
      exists of chemotherapy of locally advanced and metastatic cancer of the urinary
      bladder (UB) with gemcitabine+cisplatin over the scheme M-VAC. The data for 1990
      2002 obtained from the data base Medline, library of Cocrane Association,
      proceedings of the symposia and conferences, publications in domestic periodicals
      Urologiya, Voprosy Onkologii covered 3477 items on UB cancer. Nine publications
      were selected which seem to use significant information in terms of evidence
      based medicine. The patients were divided into two groups. Group 1 consisted of
      patients with local and metastatic UB cancer treated with the combination
      gemcitabine+cisplatin (n = 390). Group 2 patients (n = 499) received chemotherapy
      with M-VAC. By principles of evidence-based medicine, group 1 patients had more
      frequent unfavourable outcomes (absence of complete and partial regressions)--50
      and 42%, respectively. A decrease in the absolute risk is significant (p < 0.05,
      chi-square = 5.8). It is 8% in the confidence interval (CI) 4,12. A decrease in
      the relative risk was 19% (CI 13.7-24.3), odds ratio 1.39 in CI 1.3-1.48. Thus,
      at present there are no reliable data on advantages of local and metastatic UB
      cancer treatment with the scheme gemcitabine-cysplatin over standard treatment M
      VAC.

PMID- 15457945
TI  - [Treatment of epithelial tumors of the upper urinary tracts].
AB  - The authors present the results of different operative treatments of tumors of
      the upper urinary tracts (UUT). A total of 116 patients with UUT tumors were
      examined and treated from 1990 to 2002 (age 19-80 years, mean age 61.3+/- 1.3
      years; males 82, females 34). Tumors of the renal pelvis and the ureter were
      detected in 76 (65.5%) and 40 (34.5%) patients, respectively (8.0 and 4.3% of a
      total number of patients with tumors of the kidneys and UUT). 107 (92.2%)
      patients were operated. Nephroureterectomy and ureterectomy with resection of the
      urinary bladder were performed in 73 (68.2%) patients, TUR of the urinary bladder
      wall, ureteral ostium with pelvic part of the ureter and nephroureterectomy
      (including endovideosurgery) in 22 (20.6%), nephroureterocystectomy in 4 (3.7%),
      resection of the pelvic ureter with Boari's operation in 5 (4.7%), nephroscopy,
      ureteroscopy with removal of urothelial tumor in 3 (2.8%) patients. Postoperative
      complications (most of them infectious-inflammatory) developed in 10 (9.3%)
      patients. Lethality was 0.9%. Tumor recurrences occurred in 27 (25.2%) patients
      within 5-year follow-up. 15 (14.0%) patients were reoperated. 5-year survival
      reached 67.0%. Conventional and radical method of treating patients with tumors
      of the renal pelvis and ureter is nephroureterectomy with urinary bladder
      resection and its modification. In invasion of the tumor in the muscular layer of
      the bladder wall surgery should be extended and supplemented with cystectomy.
      Conservative surgical interventions are indicated in tumors of the sole kidney,
      bilateral process, benign or surface tumor of the urothelium.

PMID- 15457946
TI  - [Neoadjuvant hormone therapy with casodex in a dose 150 mg prior to radical
      prostatectomy in patients with prostatic cancer].

PMID- 15457947
TI  - [Regional metastases of penile cancer: optimal treatment policy].
AB  - Emergence of regional penile cancer (PC) metastases reduces late survival of PC
      patients from 94.4 to 83.9%. PC stage can hardly be diagnosed by clinical data
      significantly. Bilateral inguinal lymphadenectomy is indicated for all PC
      patients with enlarged and clinically negative regional lymph nodes in poorly
      differentiated primary tumor (G3) and stages T2-3. Follow-up can be recommended
      for patients with stage Tis-T1, low and moderate anaplasia (G1-2) of the primary
      tumor. Metastases to the iliac lymph nodes are an indication to pelvic
      lymphadenectomy. Preventive removal of the iliac lymph nodes in intact inguinal
      ones is not justified. Unremovable fixed regional lymph nodes should be exposed
      to radiotherapy.

PMID- 15457948
TI  - [A direct uretero-enteroanastomosis: a return to the past?].
AB  - The authors analyse their experience with ureter implantations into a small
      intestinal retaining reservoir--both direct and antireflux. From 1994 to 2004
      orthotopic replacement of the urinary bladder (UB) with an ileal segment was
      performed in 62 patients (59 males, 3 females) for UB cancer (n = 55),
      microcystis (posttraumatic, radiation-induced, tuberculous) (n = 7). Orthotopic
      replacement of the UB was made according to VIP (vesica ileale Padovano)
      technique with creation of antireflux uretero-enteroanastomoses by Le Duc (group
      1, 43 patients, 82 anastomoses) and Hautmann technique in modification of Lippert
      Theodorescu (group 2, 14 patients, 28 direct uretero-enteroanastomoses). A direct
      uretero-enteroanastomosis was performed by Nesbit and Bricker technique. Five
      patients were withdrawn from the final analysis: 3 of them died early after the
      surgery because of complications, 2 patients died due to progression within 3 and
      4 months after the operation. A total length of the ileac segment used for UB
      repair in both groups was 60 cm. Upper urinary tracts (UUT) and kidneys after the
      operation were assessed by the results of ultrasonic investigation of the
      caliceropelvic system, kidneys, UB, residual urine, serum creatinine, excretory
      urography, spiral CT (on demand), etc., after recovery of miction (3-4 weeks
      after operation), 3 and 6 (+cystography) after the operation, 12 months after the
      operation and annually. Comparison of the results of direct and antireflux
      anastomoses suggests a conclusion that a high rate of strictures due to
      antireflux anastomoses provoking UUT and renal dysfunction makes their benefit
      doubtful. Antireflux bypass ureteral surgery with neocystis of low pressure seems
      unjustified. In creation of capable uroreservoir of low pressure a direct
      implantation of the ureter into it is simple to do and less risky in respect to
      development of anastomotic stricture and damage to the renal function.

PMID- 15457949
TI  - [New fluoroquinolones in urology].
AB  - The authors review the practice of using fluoroquinolones (FQ) of the second
      generation in urology: levofloxacine, sparfloxacine, moxifloxacine. Details are
      given on chemical structure of FQ, their antimicrobial spectrum, indications for
      FQ administration, pharmacokinetics, efficacy in complicated infections of the
      urinary tracts. Treatment with new FQ demonstrated a good effect: high clinical
      and bacteriological responses (100 and 98.5%; 88.7 and 78.1%, 95.7 and 85.7% in
      the treatment with levofloxacine, sparfloxacine, moxifloxacine, respectively).
      The area of clinical application of FQ is urinary infection, urogenital
      infections, sexually transmitted diseases.

PMID- 15457950
TI  - [Dopplerographic assessment of therapeutic efficacy of incoherent quantum
      irradiation in combined therapy of acute pyelonephritis].
AB  - The authors present a comparative estimation of therapeutic efficiency of
      conventional antibacterial therapy, coherent and incoherent impulse quantum
      irradiation at a constant magnetic field in combined therapy of 130 patients with
      acute pyelonephritis. Incoherent impulsive quantum irradiation at a constant
      magnetic field showed high clinical efficacy manifesting in early normalization
      of microcirculation of the affected kidney.

PMID- 15457951
TI  - [Male genital tuberculosis in West Siberia].
AB  - Clinical picture and structure of male genital tuberculosis were analyzed basing
      on case histories of Novosibirsk regional tuberculous hospital (outpatient
      department): 42 patients with tuberculous epidydymitis and 58 patients with
      prostatic tuberculosis. Efficiency of combined etiopathogenetic treatment was
      estimated in 91 patients admitted to the Urogenital clinic of Novosibirsk
      Research Institute of Tuberculosis. These patients received polychemotherapy
      alone (control group) or in combination with laser therapy (study group).
      Combination of polychemotherapy with laser radiation proved more effective than
      polychemotherapy alone.

PMID- 15457952
TI  - [Prostatic calculi: diagnostic and therapeutic aspects].
AB  - Strength properties of prostatic calculi (PC) were studied by microhardness HV.
      Fifteen calculi under study were divided into 3 groups by the size: 2-3 mm (group
      1), 4-6 mm (group 2), > 6 mm (group 3). The surface of the thin sections of the
      calculi appeared as concentric, spherical layers of different size indicating
      formation of the calculus from the center. In the latter one could see a
      pigmented nucleus of organic nature. Some calculi had two nuclei under one cover-
      attached calculi. Correlations between the structure, morphology of prostatic
      calculi and their strength properties were established. These correlations
      allowed one to characterize destruction features of the calculi in different
      destructing impacts. We have designed and introduced into practice a complex of
      local physiotherapy in prostatolithiasis. This physiotherapy was conducted in
      combination with medicines for chronic prostatitis and included exposure of the
      prostate to ultrasound in impulse regime (4 mc, 0.4-1.0 W/cm2). The ultrasound
      was delivered through the rectum (insertion of the setting IUT 2.264-7-2.09u to
      the site of the concrements location) and alternated with laser therapy
      (insertion of the radiator P-2 into the rectum and radiator LO1 to the perineal
      area (5 W, 80 Hz, 64-128 s) and introduction of sulfide mud heated with the
      device PPK-01 Pra, electrostimulation for better passage of the prostatic
      section. The above therapy destructed the concrements which eliminated from the
      prostatic ducts as a result of which prostatic function recovered. The complex
      produced a good effect: 65% patients stated enhancement of the erectile function
      after 3 days of the treatment. After 5-6 procedures pain syndrome relieved in 40%
      patients, after 11-15 procedures in 87%. Ultrasonic investigation showed that
      posttreatment size of the prostate diminished from 0.8 to 0.2 cm. The absence of
      the calcinates's shadows were recorded in 87% patients, the symptoms of chronic
      prostatitis disappeared. The results of the combined physiotherapy demonstrate
      efficacy of the above method in true prostatoliths.

PMID- 15457953
TI  - [Famciclovir in the treatment of family herpes].

PMID- 15457954
TI  - [Botulinic toxin in patients with neurogenic dysfunction of the lower urinary
      tracts].
AB  - Botulinic toxin (BT) is a new method of lowering intraurethral pressure in
      symptoms of obstructive voiding in patients with neurogenic dysfunction of the
      lower urinary tracts (LUT). Transperineal introduction of 100 units of BT type A
      (botox, Allergan) was used under electromyographic control into the external
      urethral sphincter of 9 patients (6 males and 3 females) with LUT neurogenic
      dysfunction aged 17 to 68 years (mean age 37.2 years). Two patients had subnormal
      detrusor contractility due to myelodysplasia and diabetic polyneuropathy, two
      other patients--non-incontinent striated urethral sphincter after hemorrhagic
      stroke and spinal contusion, five patients suffered from detrusor-sphincteral
      dyssynergia (DSD) resultant from Schmorl's hernia, multiple sclerosis, Charcot
      Marie disease and ischemic stroke of the spinal cord. Three patients had
      cystostomic drainage. The rest of the patients complained of dysuria, three
      patients performed self-catheterization, mean volume of the residual urine was
      170 ml (180-240 ml). In 10 days residual urine was not found in 2 patients with
      subnormal detrusor contractility and in 4 patients with DSD. Abdominal pressure
      fell from 75 to 39 cm, on the average. In DSD patients maximal detrusor pressure
      fell from 59 to 29 cm, on the average. Mean maximal urinary flow rate rose from
      4.3 to 9.6 ml/s. In 20 days, on the average, suprapubic fistula healed in all the
      patients. In a month, therapeutic effect persisted in all the patients.
      Complications, side effects were not registered. BT treatment to induce adequate
      urine evacuation in neurological patients is a promising approach in
      neurourology. Further studies should find answers to questions about regimen of
      BT introduction, loss of sensitivity, new indications in urology.

PMID- 15457955
TI  - [Tamsulosin in the treatment of detrusor-sphincter dyssynergia of the urinary
      bladder in patients with multiple sclerosis].
AB  - Urination disorders occur in 80% patients with multiple sclerosis (MS). Most
      common of them is detrusor-sphincter dyssynergia (DSD). Alpha1-adrenoblockers can
      relax the neck of the urinary bladder (UB) and urethral sphincters, thus
      eliminating dynamic obstruction, reducing resistance to urine flow and
      facilitating voiding. Our study assessed feasibility of using a selective
      alpha1A/D-adrenoblocker tamsulosin in MS-associated DSD. The choice of this alpha
      adrenoblocker was based on its high safety profile in relation to cardiovascular
      system. The trial enrolled 28 patients (20 females and 8 males) with verified
      diagnosis of DSD. They were given tamsulosin (omnik) in a dose 0.4 mg/day (1
      capsule) for 2 months. To the end of the trial quality of life raised in 96%
      patients. Occurrence of pollakiuria, number of imperative micturate urges
      diminished, the IPSS score decreased by 54%, QL index improved by 58%. There was
      also a decrease in the volume of the residual urine, amplitude of involuntary
      detrusor contractions, an increase in maximal volumic speed of urine flow,
      cystometric volume of the UB, mean urine volume in urination. Side effects were
      not registered. Thus, tamsulosin has a positive effect in voiding disorders in
      the presence of DSD associated with MS. This considerably improves quality of
      life of MS patients.

PMID- 15457956
TI  - [Viagra effects on polysystemic energy metabolism in stress (an experimental
      study)].
AB  - Experiments on 40 white rats were made to study effects of cardura (doxasozine)
      and viagra on polysystemic energy metabolism in stress. All the animals were
      examined for cytochemical activity of succinate dehydrogenase, lactate
      dehydrogenase in blood lymphocytes, antioxidant activity of blood plasm, levels
      of hydroperoxides, malonic dialdehyde. 3-hour immobilization raises functional
      activity of mitochondria manifesting with intensification of energy metabolism.
      Adrenoreceptors blockade by cardura prevents changes in the cellular metabolism.
      The same antistress effect is observed in viagra action. This newly discovered
      mechanism may prevent complications of adrenergic reactions accompanying sexual
      intercourse.

PMID- 15457957
TI  - [Surgical treatment of vesico-ureteral reflux in complete doubling of the
      ureters].
AB  - Eleven patients aged 1 to 12 years were examined after operation of creation of
      intravesical ureter fissus (IVUF) from urinary bladder mucosa. The IVUF acts as a
      valve preventing vesico-ureteral reflux (VUR) in complete doubling of the
      ureters. One of the patients has undergone one-stage antireflux operation on
      double ureters on the right and triple ureters on the left. The operations were
      performed in VUR of the third-fourth degrees. Examination of the patients
      included excretory urography, ultrasonic investigation of the kidneys and urinary
      bladder, cystography, cystoscopy. Stenosis of the artificial ureteral ostium was
      not observed. The kidney functioned in all the patients. Urine retention, VUR
      were absent. This technique does not destruct natural ureterovesical anastomosis,
      helps reestablish an adequate valvular mechanism irrespective of ureteral
      dilatation.

PMID- 15457958
TI  - [Comparison of rotoresection and transurethral resection in the treatment of
      benign prostatic hyperplasia].
AB  - Comparison of duration, blood loss and efficacy of TUR and rotoresection in the
      treatment of benign prostatic hyperplasia has demonstrated that rotoresection
      allows almost bloodless and effective transurethral removal of prostatic
      hyperplastic tissue and, therefore, is a promising alternative to routine TUR of
      the prostate.

PMID- 15457959
TI  - [Cure of a patient with prostatic leiomyosarcoma with radiotherapy].

PMID- 15457960
TI  - [Affection of urogenital organs in Wegener's syndrome].

PMID- 15457961
TI  - [Flap urethroplasty].

PMID- 15457962
TI  - [Hepatitis 2004: an update].

PMID- 15457963
TI  - [Hepatitis A and E enterically transmitted virus infections of the liver].
AB  - Hepatitis A virus (a picornavirus) and hepatitis E virus (so far unclassified)
      are small, non-enveloped and relatively stable RNA viruses with many similar,
      yet, not identical characteristics. Both viruses are transmitted preferentially
      by the fecal-oral route. Consequently, their spread is favoured by poor personal
      hygiene and inappropriate sanitary conditions. Infection can pass subclinically,
      take an acute and self limiting course, and can also manifest as fulminant
      hepatitis with liver failure. True chronic disease is unknown. Laboratory
      diagnosis is preferentially performed by serology, but can also be complemented
      by assay for viral RNA in stool or serum. Resolution of infection leads to
      immunity which, in the case of hepatitis A, is known to be fully protective and
      most likely lifelong. Available hepatitis A vaccines are able to induce a similar
      state of protection. Vaccines for hepatitis E are under development. Specific
      antiviral treatment is not yet available, neither for hepatitis A nor for
      hepatitis E.

PMID- 15457964
TI  - [Management of hepatitis B].
AB  - Treatment of chronic hepatitis B needs to consider two aspects. First, a certain
      proportion of patients will spontaneously undergo a stable remission of the
      underlying liver disease, i.e. without therapeutic intervention, on occasion of
      the HBeAg --> anti-HBe seroconversion. Second, all drugs that have been used so
      far in the treatment of HBV have rarely resulted in the definitive eradication of
      the viral infection, i.e. a permanent disappearance of HBsAg with development of
      anti-HBs. Thus, the most reasonable, albeit surrogate endpoint of treatment is
      the acceleration towards HBeAg --> anti-HBe seroconversion and/or the stable
      suppression of HBV replication at levels below 500000 copies/ml, which is
      associated with disappearance of intrahepatic necrosis and inflammation and
      slowing down of the fibrosis progression. Two drugs are currently available-
      interferon-alpha and lamivudine--and a third antiviral compound (adefovir
      dipivoxil) will soon appear in the market. Advantages and disadvantages of
      different therapeutic options are discussed below.

PMID- 15457965
TI  - [Hepatitis C].
AB  - Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver
      cirrhosis, and hepatocellular carcinoma worldwide. Here, we briefly review the
      virology, diagnosis and therapy of hepatitis C. Standard therapy with pegylated
      interferon-alpha and ribavirin results in a sustained virological response in 40
      50% of genotype 1- and in about 80% of genotype 2- or 3-infected patients. Recent
      progress has allowed the identification of novel antiviral targets and
      therapeutic strategies. These will likely complement existing therapeutic
      modalities in the near future.

PMID- 15457966
TI  - [Autoimmune hepatitis].
AB  - Autoimmune hepatitis (AIH) is chronic, predominantly periportal hepatitis with
      hypergammaglobulinemia and tissue autoantibodies. It is a relative rare disorder,
      with a preponderance of female patients, that can present at any age. Its
      diagnosis relies on the exclusion of viral, metabolic, genetic and toxic
      etiologies of chronic hepatitis or hepatic injury. There are no pathognomonic
      features, but the presence of antinuclear and smooth muscle antibodies or liver
      kidney microsomal antibodies together with typical histological features in liver
      biopsy allows the diagnosis with good confidence. Corticosteroid therapy is
      effective in most patients. Because of a favorable side effect profile, the
      combination therapy with azathioprine should be used whenever possible. Relapses
      after initial treatment responses are frequent, but in the majority of patients
      the disease can be controlled. Liver transplantation is effective, and shows good
      10-year survival rates.

PMID- 15457967
TI  - [Alcoholic and non-alcoholic steatohepatitis].
AB  - Chronic aethylism has always been a major social as well as health problem. It
      may lead, at least in some patients, to steatohepatitis (ASH) which is known to
      progress to cirrhosis more rapidly. Because of the fact that the prevalence of
      obesity in association with the metabolic syndrome (insulin resistance) is
      strikingly increasing in the Western world, we will more and more often be faced
      with a second form of steatohepatitis, the so called non-alcoholic
      steatohepatitis (NASH). Clinical differentiation between these two entities may
      often be difficult. The use of the CAGE-questions as well as interviewing family
      members can help to indentify hidden alcohol abuse. Clinically, the presence of
      both diseases can only be speculated. To get the diagnosis, liver biopsy must be
      performed to show the typical histologic feature of fatty liver with hepatocyte
      necrosis as well as infiltration of polymorphcellular leukocytes. Histology
      cannot differentiate between ASH and NASH. Therefore, similar pathogenetic
      mechanisms are supposed. However, therapeutic approaches are different. Treatment
      of choice in ASH is alcohol abstinence, that of NASH the reduction of insulin
      resistance, primarily by weight loss.

PMID- 15457968
TI  - [Hereditary liver diseases].
AB  - In recent years the identification and characterization of gene defects
      underlying hereditary liver diseases lead to a better understanding of their
      pathogenesis. Heditary hemochromatosis, Wilson's disease and alpha1-antitrypsin
      deficiency are the most common hereditary liver diseases. While gene defects and
      disease manifestation may correlate, genetic testing is generally not
      contributing to diagnosis. This review summarizes the clinical manifestations,
      diagnosis and therapy of the most frequent hereditary liver diseases: hereditary
      hemochromatosis, Wilson's disease and alpha1-antitrypsin deficiency.

PMID- 15457969
TI  - [Cholestatic liver diseases].
AB  - Primary biliary cirrhosis (PBC), autoimmune cholangitis (AIC = AMA-negative PBC)
      and primary sclerosing cholangitis (PSC) are autoimmune cholestatic liver
      diseases. Overlap syndromes combine characteristics of cholestatic liver diseases
      and autoimmune hepatitis. In PBC, alkaline phosphatase and gamma-glutamyl
      transferase are elevated, to a lesser degree aminotransferases. Histology shows
      bile duct lesions. Anti-mitochondrial antibodies are typical. Ursodeoxycholic
      acid (UDC) is established therapy that slows or even stops the disease
      progression, at least in early stages of the disease. In non-responders
      immunosuppression is recommended. PSC is mostly associated with chronic
      inflammatory bowel diseases. P-ANCA are frequent. Bile duct lesions revealed by
      retrograde cholangiography are characteristic. UDC is given as therapy. Bile duct
      strictures or bacterial cholangitis may be late sequelae and should be treated by
      antibiotics or bile-duct dilatation. Cirrhosis may ultimately develop in PBC and
      PCS. In progressed PBC or PSC liver transplantation is indicated.

PMID- 15457970
TI  - [Toxic liver injuries].
AB  - Drug induced hepatotoxicity is clinically important for several reasons. These
      forms of liver injury can mimic almost all other liver diseases, making it
      necessary to include them into the differential diagnosis in patients with
      unclear liver damage. The diagnosis must be made indirectly, by judging the
      temporal relationship with therapy and by exclusion of other liver diseases. Re
      exposure is dangerous should be avoided. Knowledge of the most important risk
      factors is important for avoiding drug-induced liver injury. Since there is no
      specific therapy for most drug-induced liver injuries, early stopping of the
      administration of suspected drugs is very important.

PMID- 15457971
TI  - Burden of proof.

PMID- 15457972
TI  - Effective communication. The best defense for your practice.

PMID- 15457973
TI  - Advertising by any other name...

PMID- 15457974
TI  - Just for the fun of it.

PMID- 15457975
TI  - Fight licensure abuse.

PMID- 15457976
TI  - Preparing for a terrorist event: a scenario-driven approach.
AB  - Since September 11, 2001, government agencies on all levels have focused on
      planning and preparing to respond to another possible terrorist attack. In
      addition to emergency and medical issues, these agencies must be concerned about
      the public's behavior and psychological response when they plan the management of
      a bioterrorist event. We present readers with one such possible incident, a
      radiological bomb scenario, with the aim of educating dentists and communicating
      the risks involved.

PMID- 15457977
TI  - Treatment planning considerations for the endodontically compromised tooth.
AB  - Recent advances in microendodontic procedures have dramatically enhanced our
      ability to successfully retreat most endodontic failures, either surgically or
      nonsurgically. Ironically, this comes at a time when we are seeing an increasing
      tendency to forego heroic endodontic procedures in favor of a single-tooth
      implant. While an implant has proved to be a reliable replacement for a missing
      tooth, it should not be considered the true equivalent of a functional natural
      tooth. Whenever the possibility of retaining a functional tooth exists, it should
      be considered seriously before an ultimate decision is made.

PMID- 15457978
TI  - Convergence towards higher standards in international dental education.
AB  - This paper emanates from the findings of "DentEd" and "DentEdEvolves," two
      sequential European Union-funded Thematic Network Projects on Dental Education.
      Despite the existence of EU Directives and Guidelines, which were devised to
      assure comparable and acceptable standards of dental education and competence
      gained from training programs, there are serious differences among countries. The
      differences are greater in those countries about to join an expanding EU, where
      the stomatological approach to education predominates. Both projects had
      considerable support and advice from the Association from Dental Education in
      Europe, the American Dental Education Association and the International
      Federation of Dental Education Associations. An international effort is now
      proposed to converge towards higher standards in dental education by agreeing to
      broad principles for the "Profile of an International Dentist" (see
      www.dented.org/dresden.php3). The UK's General Dental Council recently adopted
      its profile of a dentist, which is compatible with and related to the EU's Dental
      Directives and Guidelines (see www.gdc-uk.org/pdfs/first_five_years_2002.pdf). An
      agreed profile provides a basis on which to structure a pan-European approach and
      could be more widely adopted. Dental schools throughout the world might be asked
      to verify those elements with which their graduates actually comply. It is also
      intended to use the profile as a basis for a modularized approach that would
      facilitate students studying elements of their course in different universities
      as part of an EU drive towards convergence in third- level education. It is not
      intended to promote a single educational approach. Unfortunately, at this stage,
      it will have little impact on global ill health, mainly associated with poverty
      and more recently the HIV/AIDS pandemic. The University of Columbia's Earth
      Centre has made enormous strides in focusing attention on global health and
      deprivation. Almost one-sixth of the world's population is starving. In sub
      Saharan Africa, where poverty is exacting its greatest toll, the HIV/AIDS
      pandemic is devastating populations, including health care workers.
      Realistically, our impact as dental educators on global health will be limited.
      Nevertheless, a better educated and understanding profession is more likely to
      apply the benefits of knowledge, science and affluence to help those most in
      need.

PMID- 15457979
TI  - Tobacco cessation within the dental curriculum in the United States and
      internationally.
AB  - Tobacco use is a worldwide public health issue with enormous costs in morbidity
      and mortality. Dentists are in a unique position as health care providers to
      offer tobacco cessation counseling to their patients. In order to do so,
      clinicians must be properly trained in tobacco cessation skills. The onus falls
      upon professional schools to include information about tobacco use, its clinical
      effects, and ways to help patients quit into the dental curriculum. In the past
      15 years, there has been an increase in the number of dental schools that have
      adopted anti-tobacco policies and included tobacco in their clinical courses both
      here in the United States and in Europe. Dental schools with functional tobacco
      cessation programs in place must follow up on the activities conducted in their
      clinics to ensure that dental students are appropriately employing the correct
      techniques and, thus, learning to provide optimal care to their patients.

PMID- 15457980
TI  - Problem-based learning definition, implementation and opportunities for
      collaboration.
AB  - Since first being implemented more than 30 years ago, problem-based learning has
      become an increasingly popular approach to education. More and more dental
      schools in the United States and internationally are implementing some aspect of
      PBL into their curriculum. This paper will define PBL, describe how it is
      implemented within various institutions and discuss the potential for using PBL
      as the basis for collaboration among institutions.

PMID- 15457981
TI  - Build your practice with "paid-for dentistry". Solving the mystery of patient
      financing.

PMID- 15457982
TI  - The National Morbidity, Mortality, and Air Pollution Study. Part III: PM10
      concentration-response curves and thresholds for the 20 largest US cities.
AB  - Numerous studies have shown a positive association between daily mortality and
      particulate air pollution, even at concentrations below regulatory limits. These
      findings have motivated interest in the shape of the concentration-response
      relation. We developed flexible modeling strategies for time-series data that
      include spline and threshold concentration-response models. We applied these
      models to daily time-series data for the 20 largest US cities for 1987 through
      1994, using concentration of particulate matter less than 10 microm in
      aerodynamic diameter (PM10*) as the exposure measure. The spline model showed a
      linear relation without indicating a threshold for the relative risks of death
      for all causes (total deaths) and for cardiovascular-respiratory causes in
      relation to PM10 concentration. By contrast, for causes other than cardiovascular
      respiratory, the relative risk did not increase until the concentration reached
      approximately 50 microg/m3 PM10. For total mortality, a linear model without
      threshold was preferred to the threshold model and to the spline model, using the
      value of the Akaike information criterion (AIC). The findings were similar for
      combined cardiovascular and respiratory deaths. These findings indicate that
      linear models without a threshold are appropriate for assessing the effect of
      particulate air pollution on daily mortality even at current ambient levels.

PMID- 15457983
TI  - [Hemorheology and physiological function--hemodynamics and blood viscosity].

PMID- 15457984
TI  - [Treatment of hypopharyngeal carcinomas--an institutional analysis of the results
      of FAR radiochemotherapy, radical resection, and free jejunum flap reconstruction
      and the indication of neck dissection].
AB  - The treatment results of 65 patients with hypopharyngeal carcinomas treated at
      our institute between 1995 and 2000 were analyzed. In general, concurrent
      radiochemotherapy (RCT), consisting of intravenous 5-FU injection, intra-muscular
      vitamin A injection, and radiation (FAR therapy) was used as an initial treatment
      for advanced hypopharyngeal carcinomas and early hypopharyngeal carcinomas. Tumor
      responses were evaluated at the time of radiation doses of 30Gy. Patients who
      showed a complete response (CR) subsequently received curative radiation doses of
      60 to 70Gy. Patients who did not show a CR underwent radical surgery consisting
      of pharyngo-laryngo-cervical esophagectomy, neck dissection for positive cervical
      nodes and/or the primary tumor sides, and reconstruction using a free jejunum
      flap. The disease-specific 5-year survival rates were 92%, 55%, 35% and 49% for
      stage I/II, III, IV and all cases, respectively. Eight out of 9 patients with
      stage I/II disease who showed a CR after receiving 30Gy of RCT survived with an
      intact larynx after definitive RCT. All the patients with stage II/III disease
      who underwent radical surgery after receiving 30Gy of RCT did not have a
      recurrence, whereas the 5-year survival rate of patients with stage IV disease
      who underwent RCT and radical surgery was 45%. Seventeen out of 19 patients with
      clinically negative cervical nodes on the opposite side of their primary tumors
      showed no nodal metastasis after RCT without neck dissection. This result
      suggests that elective neck dissection after RCT is not necessary. To improve the
      treatment results for hypopharyngeal carcinomas, early detection of this disease
      is prerequisite. In addition, the clinical diagnosis of highly malignant cases
      and new molecular-targeted therapies based on an analysis of distant metastasis
      mechanisms should be developed to overcome the poor prognosis of advanced
      hypopharyngeal carcinomas.

PMID- 15457985
TI  - [Surgical treatment of patients with severe obstructive sleep apnea syndrome].
AB  - No standard indications currently exist for surgical treatment of severe
      obstructive sleep apnea syndrome (OSAS). We treated 15 patients with severe OSAS
      surgically, evaluated surgical indications, and evaluated surgical success. We
      retrospectively reviewed 15 cases of surgery for OSAS in which polysomnography
      met 2 or more criteria for the following surgical indications: (1) apnea hypopnea
      index (AHI) > or = 50, (2) minimum SpO2 below 80%, and (3) enlarged tonsils
      (grade III, Mackenzie's classification). Among the 15, mean AHI was 85.1. Surgery
      was done under general anesthesia, with uvulopalatopharyngoplasty (UPPP) in 13
      and tonsillectomy alone in 2. Postoperative AHI was measured in 9 patients.
      According to Nishimura's criteria for assessing surgical success, improvement was
      "excellent" in 5, "good" in 1, "fair" in 1, and "poor" in 2. When we compared
      preoperative and postoperative use of continuous positive airway pressure (CPAP)
      in 7, we found that surgery decreased CPAP requirements. Surgical success was
      assessed in patients requiring CPAP and improvement was "excellent" in 5, "good"
      in 1, and "fair" in 1. In conclusion, surgical indications for severe OSAS,
      including the criterion of enlarged tonsils, were useful. Surgery decreased CPAP
      requirements and the degree of improvement in this requirement and AHI was
      valuable in assessing surgical success.

PMID- 15457986
TI  - [Clinical study on papillary thyroid carcinoma presenting with lymph node
      metastasi].
AB  - Papillary thyroid carcinoma (PTC) may metastasize to cervical lymph nodes. It is,
      however, uncommon for a palpable neck node alone to lead to the diagnosis of this
      disease when it is not apparent at presentation. Standard treatment for such
      cases has not yet been established. We retrospectively analyzed clinical courses
      in 8 patients with thyroid papillary carcinoma presenting with palpable lymph
      node metastasis at Hokkaido University Hospital between 1990 and 2003. Three had
      high thyrogloblin in cervical cystic lesions, leading to the diagnosis of PTC
      with lymph node metastasis. In 4, PTC was diagnosed by pathological examination
      of cervical lymph nodes initially diagnosed as lateral cervical cysts.
      Preoperative examination did not indicate PTC within the gland in any case. All 8
      were alive at the last visit after follow-up from 23 to 150 months (mean: 78
      months). Total thyroidectomy was done on 4 and thyroid lobectomy on 3.
      Pathological examination of resected thyroid glands confirmed multifocal
      papillary carcinoma from 4 mm to 15 mm in diameter. Six underwent unilateral neck
      dissection and 1 chose bilateral dissection. The other patient received no
      additional surgery on either the thyroid or neck after the single enlarged lymph
      node initially diagnosed as a lateral cervical cyst was resected. Postoperative
      radioiodine treatment was done in 2 undergoing total thyroidectomy. Recurrence in
      the cervical area were observed in 1 whose neck dissection was insufficient.
      Based on these observations, we concluded that patients who undergo thyroid
      lobectomy and adequate neck dissection may enjoy longer survival than those
      treated with total thyroidectomy without sacrificing thyroid and parathyroid
      function. We therefore propose a prospective study on the effectiveness of
      thyroid lobectomy with neck dissection including positive nodes in patients with
      occult PTC presenting with lymph node metastasis.

PMID- 15457987
TI  - [Case of recurring middle ear adenoma].
AB  - We report a case of recurring middle ear adenoma with bone formation that was
      histologically difficult to differentiate from adenocarcinoma. The patient was a
      31-year-old female. Preoperative clinical and CT findings in the 31-years-old
      woman examined suggested benign tumor of the middle ear. Although intraoperative
      pathological examination indicated adenocarcinoma, tympanoplasty in canal
      reconstruction was done. Malignancy was not considered because the tumor had not
      increased in size for 1 year and no bone erosion had occurred in the ossicles or
      middle ear cleft. The definitive pathological diagnosis was middle ear adenoma.
      The tumor repeatedly recurred thereafter, closely resembling normal middle ear
      mucosa and making it difficult to remove completely. When middle ear adenoma is
      suspected, surgical procedures should be determined carefully based on
      radiological and intraoperative findings in tumor expansion.

PMID- 15457988
TI  - [Molecular diagnosis in ophthalmology].

PMID- 15457989
TI  - [Short and long-term hypotensive effect of timolol-gel and latanoprost
      instillation in normal-tension glaucoma].
AB  - PURPOSE: To confirm the predictive value of the results of a 4-week trial of
      latanoprost alone, timolol-gel alone, or a combination of the two in normal
      tension glaucoma (NTG) patients, when compared with the hypotensive response
      after a 6-month trial using the same combination of eye drops for the same
      patients. METHODS: One eye each of 45 NTG patients was used in a prospective 4
      week trial of latanoprost alone, timolol-gel alone, or a combination of the two.
      Patients continued using the eye drops for 6 months, according to the results of
      the trial. The correlation of the results of the 6-moth use and the baseline
      data, and the baseline data and the results of the 4-week trial were evaluated by
      the paired-t test. RESULTS: The intraocular pressure(IOP)s of patients using
      timolol-gel alone were 13.9 mmHg at the base line, 9.7 mmHg after the trial, and
      12.0 mmHg after 6-month use(baseline, trial: p < 0.05). IOPs when using
      latanoprost alone were 15.3 mmHg at baseline, 11.7 mmHg after the trial, and 11.5
      mmHg after 6-month use(baseline: p < 0.05, trial: p = 0.33). IOPs using timolol
      gel and latanoprost in combination were 14.8 mmHg at baseline, 11.4 mmHg after
      the trial, and 12.0 mmHg after 6-month use (baseline: p < 0:05, trial: p = 0.14).
      CONCLUSION: The result of the 4-weeks trial of latanoprost alone or in
      combination with timolol-gel can be indicative of the IOP after 6-month use.

PMID- 15457990
TI  - [Genetic diagnosis of retinoblastoma by a combination of fluorescence in situ
      hybridization and restriction fragment length polymorphism].
AB  - PURPOSE: It is important to exclude germ line mutation in cases of unilateral
      retinoblastoma(RB) to estimate hereditary or possible secondary cancer. We
      investigated whether genetic diagnosis is feasible in a health check screening
      program. METHODS: Five patients with RB had surgery for enucleation in Keio
      University Hospital. Tumor cells from enucleated eyes and lymphocytes
      representing systemic cells were collected and analyzed genetically by
      fluorescence in situ hybridization(FISH) and restriction fragment length
      polymorphism (RFLP). RESULTS: One out of three unilateral RB cases could be
      diagnosed as non-hereditary by the finding of no copies of the RB gene in the
      tumor cells using the FISH method and no signal in the RFLP method. A decrease of
      signal in tumor cells to less than 50% in the RFLP method was observed in another
      case of unilateral RB that seemed to be non-hereditary, but the case ultimately
      could not be diagnosed as non-hereditary because polycopies were found in the
      FISH method. No abnormality in tumor cells could be found in another unilateral
      case or in systemic cells of two bilateral cases. CONCLUSION: A combination of
      FISH and RFLP methods can be used to diagnose some cases of RB as non-hereditary.

PMID- 15457991
TI  - [A protanomalous female whose genotype of red/green visual pigment genes was
      determined by molecular analysis of her family members].
AB  - PURPOSE: To determine X-linked red/green visual pigment gene arrays of a female
      proband with protan deficiency. METHODS: We examined a brother and both parents
      as well as the proband. Severity, severe or mild form, of color vision deficiency
      was estimated with either failure or passing of the Farnsworth Panel D-15 test.
      Diagnosis of either anomalous trichromacy or dichromacy was performed using a
      Nagel Type I anomaloscope. Genotypes of red/green visual pigment genes were
      determined by quantitative polymerase chain reaction-single strand conformation
      polymorphism analysis. RESULTS: Color vision tests revealed that the proband, her
      brother, her father, and her mother had protanomaly(mild form), protanopia,
      protanomaly(severe form), and normal color vision, respectively. In analysis of
      gene arrays, the brother had a red-green hybrid gene(R1G2, Ser 180) and three
      green visual pigment genes, while the father had a red-green hybrid gene(R4G5,
      Ser 180) and a green visual pigment gene. CONCLUSIONS: It is impossible to
      directly determine each paternal or maternal X-linked red/green pigment gene
      array in the female proband. Molecular analysis of the family members revealed
      that the proband was a compound heterozygote for two R1 G2 and R4G5 hybrid genes
      encoding photopigments with different absorption maxima.

PMID- 15457993
TI  - MR perfusion imaging: a tool for more than stroke.

PMID- 15457994
TI  - Importance of CE-MRA in various body regions: comparison with i.a. DSA.

PMID- 15457995
TI  - Gadobutrol, a highly concentrated MR-imaging contrast agent: its physicochemical
      characteristics and the basis for its use in contrast-enhanced MR angiography and
      perfusion imaging.

PMID- 15457996
TI  - Quality of diagnostic information in vascular diseases.

PMID- 15457997
TI  - On the difference between 0.5-M and 1.0-M gadolinium chelates for 3D MR
      angiography.

PMID- 15457998
TI  - Peripheral contrast-enhanced 3D MRA with 1.0 M gadobutrol.

PMID- 15457999
TI  - Whole-body CE-MRA with Gadovist.

PMID- 15458000
TI  - CE-MRA of the aorta.

PMID- 15458001
TI  - CE-MRA of the kidneys.

PMID- 15458002
TI  - Pulmonary CE-MR angiography and perfusion imaging.

PMID- 15458003
TI  - Circle of Medicaid-eligible caregivers broadens.

PMID- 15458004
TI  - Executive chefs spice up nursing facilities.

PMID- 15458005
TI  - Keeping violent behavior in check.

PMID- 15458006
TI  - Connecting the dots in search of quality.

PMID- 15458007
TI  - When eviction becomes necessary.

PMID- 15458008
TI  - Men--the weaker sex? Unexpected results of a systematic review on work exposures
      and musculoskeletal disorders.

PMID- 15458009
TI  - Gender differences in the relations between work-related physical and
      psychosocial risk factors and musculoskeletal complaints.
AB  - Gender differences in the prevalence of musculoskeletal complaints might be
      explained by differences in the effect of exposure to work-related physical and
      psychosocial risk factors. A systematic review was conducted to examine gender
      differences in the relations between these risk factors and musculoskeletal
      complaints. Several electronic databases were searched. The strength of the
      evidence was determined on the basis of the methodological quality and
      consistency of the study results. For lifting, strong evidence was found that men
      have a higher risk of back complaints than women. The same was found for the
      relation between hand-arm vibration and neck-shoulder complaints. For arm
      posture, strong evidence was found that women have a higher risk of neck-shoulder
      complaints than men. For social support, no evidence of a gender difference was
      found for either neck-shoulder or back complaints. For hand-wrist and lower
      extremity complaints, inconclusive evidence was found due to a lack of high
      quality studies.

PMID- 15458010
TI  - Work-related risk factors for the incidence and recurrence of shoulder and neck
      complaints among nursing-home and elderly-care workers.
AB  - OBJECTIVES: This study assessed the differences and similarities in the incidence
      and recurrence of shoulder and neck complaints with respect to work-related
      physical, psychosocial, and personal risk factors. METHODS: A prospective cohort
      study was carried out among 769 workers of nursing homes and homes for the
      elderly. At baseline, a questionnaire was used to collect data on personal
      characteristics, physical workload, psychosocial workload, and the presence of
      shoulder and neck complaints. After 1 and 2 years, follow-up data were collected
      on shoulder and neck complaints. Generalized estimation equations were used for
      analyzing risk factors for the participants with at least one follow-up
      measurement available (N=556, 72%). RESULTS: In the multivariate model, adjusted
      for age and gender, obesity [odds ratio (OR) 2.12, 95% confidence interval
      (95%CI) 1.23-3.65] was related to the incidence of shoulder complaints. The
      incidence of neck complaints was increased for obesity (OR 1.81, 95% CI 1.07
      3.05), work in awkward postures (OR 1.76, 95% CI 1.11-2.78), and poor or fair
      general health (OR 1.53, 95% CI 1.02-2.31). The recurrence of both shoulder and
      neck complaints was associated with chronic complaints at baseline (shoulder: OR
      1.91, 95% 1.36-2.67; neck: OR 1.71, 95% 1.14-2.55) but not with work-related risk
      factors. CONCLUSIONS: The results suggest that there are differences in risk
      factors for the incidence and recurrence of shoulder and neck complaints.

PMID- 15458011
TI  - Perceived health as a predictor of early retirement.
AB  - OBJECTIVES: This study examined the association between perceived health and
      early retirement. METHODS: A cohort of 1748 men aged 42 to 60 years from eastern
      Finland was followed from 1984 to 2000. At baseline, the participants had
      answered a questionnaire regarding their general (as measured by physician
      diagnoses) and perceived health status. Comprehensive pension records were
      obtained from the Social Insurance Institution of Finland and the Central Pension
      Security Institute. The risk of disability pensioning in various disease
      categories and nonillness-based early pensioning was analyzed using Cox
      regression modeling. RESULTS: Over 11 years, 855 (48.9%) men received a
      disability pension, and 331 (18.9%) received a nonillness-based early pension.
      Only 273 (15.6%) received an old age pension, without previous early pensioning.
      At the end of the follow-up, 289 (16.5%) were still working. After adjustment for
      potential confounders, men with poor perceived health at baseline had a relative
      risk of 2.37 [95% confidence interval (95% CI) 1.79-3.13] for disability
      pensioning and the highest risk of disability was due to mental illness (RR 3.84,
      95% CI 1.86-7.92), followed by musculoskeletal disorders and cardiovascular
      diseases. The relative risk of receiving a nonillness-based pension was 2.94 (95%
      CI 1.92-4.50) for this group. CONCLUSIONS: Self-assessed poor health is a strong
      predictor of early retirement due to mental disorders, musculoskeletal disorders,
      and cardiovascular diseases. Moreover, the risk of retirement on a nonillness
      based pension is increased among those with poor perceived health.

PMID- 15458013
TI  - Sleep strategies of 12-hour shift nurses with emphasis on night sleep episodes.
AB  - OBJECTIVES: Episodes of sleep during a nightshift are frequently reported in
      various types of jobs. This phenomenon has been seldom documented so far. This
      field study investigated individual differences in the sleep-wake behavior of
      nurses. METHODS: A group of eight nurses working in an intensive care unit on a
      two 12-hour shift system kept a "sleep diary" for 1 month, recording main sleep
      periods and naps. They subjectively assessed sleepiness, sleep quality, and the
      need for sleep at various times of the day and night. Continuous actimetric
      measurements provided an evaluation of the rest-activity patterns and of the
      sleep parameters. RESULTS: Half of the nurses chose to take naps in 75% of their
      nightshifts. No differences between the night-nappers and nonnight-nappers were
      found for either total sleep length or the temporal patterns of subjective
      sleepiness at night but, during nightwork, night-nappers needed sleep earlier
      than nonnight-nappers. They had long naps during a worknight and short daytime
      sleep, sometimes followed by a late afternoon nap. This strategy probably favored
      the maintenance of a diurnal orientation. Nonnight-nappers had long daytime sleep
      and took preventive naps to anticipate sleepiness during nightwork. However,
      their readjustment to diurnal life seemed more difficult than that of night
      nappers. CONCLUSIONS: Nurses use different sleep-wake strategies to cope with
      nightwork. These different strategies may be due to circadian influence although
      social factors cannot be totally excluded.

PMID- 15458012
TI  - Exposure to urban nitrogen dioxide pollution and the risk of myocardial
      infarction.
AB  - OBJECTIVES: This study attempted to determine whether long-term exposure to
      nitrogen dioxide (NO2), an indicator of motor vehicle exhaust, increases the risk
      of myocardial infarction (MI). METHODS: A population-based case-control study was
      conducted among men aged 25-64 years and residing in Kaunas, Lithuania. The study
      included all cases of first-time myocardial infarction in 1997-2000. Interviews
      with patients treated in hospitals elicited information on smoking and other risk
      factors, including residential histories. A high response rate (77.4%) resulted
      in 448 cases and 1777 controls. Nitrogen dioxide (NO2) was selected for analysis
      as an indicator of traffic-related air pollution. The annual air pollution levels
      were estimated for the residential districts; thereafter the data were linked to
      the home addresses of the cases and controls. RESULTS: After adjustment for age,
      education, smoking, blood pressure, body mass index, marital status, and
      psychological stress, the risk of myocardial infarction was higher for the men
      exposed to medium [odds ratio (OR) 1.43, 95% confidence interval (95% CI) 1.04
      1.96] and high (OR 1.43, 95% CI 1.07-1.92) NO2 levels. The data suggested a
      stronger association among 55- to 64-year-old men. The risk of myocardial
      infarction increased by 17% among the 25- to 64-year-old men (OR 1.17, 95% CI
      1.01-1.35) and by 34% among those aged 55-64 years (OR 1.34, 95% CI 1.08-1.67)
      from the first to the third tertile of NO2 exposure. CONCLUSIONS: The results
      indicate that urban NO2 pollution may increase the risk of myocardial infarction
      and that vehicle emissions may be of particular importance.

PMID- 15458014
TI  - Evaluation of exposure biomarkers from percutaneous absorption of N-methyl-2
      pyrrolidone.
AB  - OBJECTIVES: The aim of this study was to evaluate different biomarkers of
      exposure to N-methyl-2-pyrrolidone (NMP), a widely used industrial chemical. For
      this purpose, differences in toxicokinetics between men and women and between
      pure and water-mixed NMP were evaluated after dermal absorption. METHODS: Six
      female and six male volunteers (groups 1 and 2) were topically exposed for 6
      hours to 300 mg of NMP. An additional group of six male volunteers (group 3) was
      exposed to 300 mg of NMP in a 50% water solution. Blood and urine were sampled
      before, during, and up to 9 days after the exposure. Plasma and urine were
      analyzed using mass spectrometry. RESULTS: For groups 1 and 2, 16% and 18% of the
      applied dose were recovered in the urine as the sum of NMP and its metabolites.
      For group 3, 4% was recovered. The maximal concentration of 5-hydroxy-N-methyl-2
      pyrrolidone (5-HNMP) was 10, 8.1, and 2.1 micromol/l for groups 1, 2 and 3,
      respectively, in plasma and 420, 360 and 62 micromol/l in urine adjusted for
      density. For 2-hydroxy-N-methylsuccinimide (2-HMSI), the maximal concentration
      was 5.4, 4.5, and 1.3 micromol/l for groups 1, 2 and 3, in plasma, respectively,
      and 110, 82 and 19 micromol/l in urine adjusted for density. For 5-HNMP there was
      a difference in time to reach the maximal concentration depending on whether pure
      NMP or 50% NMP in water was used. No such difference was seen for 2-HMSI. The
      differences in kinetics between male and female volunteers were small.
      CONCLUSIONS: Preferably 2-HMSI should be used as the biomarker of exposure to
      NMP.

PMID- 15458015
TI  - Acute respiratory effects of exposure to ammonia on healthy persons.
AB  - OBJECTIVES: This study investigated the acute respiratory effects of low ammonia
      exposure on healthy persons. METHODS: Twelve healthy persons underwent sham or
      ammonia (5 and 25 ppm) exposure randomly in an exposure chamber on three
      occasions. The exposure duration was 3 hours, 1.5 hours resting (seated) and 1.5
      hours exercising (50 W on a bicycle ergonometer). Symptoms were registered
      repeatedly before, during, and after the exposure on visual analogue scales.
      Bronchial responsiveness to methacholine, lung function, and exhaled nitric oxide
      (NO) were measured before and 7 hours after the exposure. In addition, nasal
      lavage was performed, and peripheral blood samples were drawn before and 7 hours
      after the exposure. RESULTS: All the symptom ratings increased significantly
      during 25-ppm ammonia exposure as compared with the control exposure. The
      cumulative dose of methacholine causing a 20% decrease in forced expiratory
      volume in 1 second was lower (<1 concentration step of methacholine) for the
      exposure than for a pretrial control challenge. However, no difference was found
      between the control and ammonia exposures (P=0.33). The ammonia exposure did not
      significantly influence lung function or the exhaled NO levels. The total cell or
      interleukin-8 concentration in nasal lavage fluid did not change. The total
      leucocyte concentration in peripheral blood increased significantly (P<0.001)
      after both the sham and ammonia exposure, mainly due to an increase in
      neutrophils (P<0.001). Ammonia exposure did not significantly alter complement
      factor 3b in plasma. CONCLUSIONS: During ammonia exposure in an exposure chamber,
      symptoms related to irritation and central nervous effects increase and are
      constant with no signs of adaptation. Ammonia inhalation does not cause
      detectable upper-airway inflammation or increased bronchial responsiveness to
      methacholine in healthy persons.

PMID- 15458016
TI  - Prevention of acute mountain sickness by low positive end-expiratory pressure in
      field conditions.
AB  - OBJECTIVES: This study evaluates the ability of positive end-expiratory pressure
      (PEEP), a nonpharmacological method, to prevent the occurrence of acute mountain
      sickness during two ascents of Mount Blanc. METHODS: In a random order (once with
      PEEP and once without), PEEP was administered or not to eight subjects during two
      ascents of Mount Blanc. Scores for acute mountain sickness were quantified using
      the Lake Louise acute mountain sickness scoring system, and oxygen arterial blood
      saturation by pulse oxymetry (SpO2), heart rate, and systolic and diastolic blood
      pressures were also measured. RESULTS: The decrease in the prevalence of acute
      mountain sickness indicated that the PEEP system was effective, one case (12.5%)
      occurring among the eight participants with PEEP and six cases (75%) occurring
      among the eight without PEEP (P<0.01). The severity of the cases also decreased
      (P<0.01). Heart rate and blood pressure did not significantly vary, whereas the
      SpO2 tended to be higher with PEEP (P=0.07). CONCLUSIONS: This field study shows
      that PEEP could be an efficient method with which to prevent acute mountain
      sickness without adverse effects. However, the ergonomics of the PEEP system must
      be improved to make its use more practical in the future.

PMID- 15458017
TI  - Information demands of occupational health physicians and their attitude towards
      evidence-based medicine.
AB  - OBJECTIVES: This study assessed the extent and nature of information demands
      among occupational health physicians and their attitude towards the application
      of evidence-based medicine in occupational health. METHODS: A questionnaire
      survey was carried out among a random sample of 159 physicians practicing
      occupational medicine in The Netherlands. The questionnaire investigated the type
      and number of questions encountered in daily practice, the actions taken in
      response, the physicians' experience in using scientific databases on the
      Internet, and their attitude towards evidence-based medicine. RESULTS: The
      occupational health physicians' questions concerned medical, legal, and
      rehabilitation topics in particular. In pursuing answers to their questions, they
      generally chose to contact colleagues. Scientific databases were not consulted
      very often, although, in general, the attitude towards evidence-based medicine
      was positive. In addition to known barriers for practicing evidence-based
      medicine, occupational health physicians perceive a lack of scientific evidence
      in their field. The extensiveness of the field of knowledge in occupational
      health care was not regarded as an obstacle to their application of evidence
      based medicine. CONCLUSIONS: Occupational health physicians have a demand for
      information on a broad range of topics, and, in most cases, their attitude
      towards evidence-based medicine is fairly positive. Besides education and
      training in evidence-based medicine, access to the Internet and the presence of a
      good knowledge infrastructure would help occupational health physicians use
      evidence-based medicine.

PMID- 15458018
TI  - Prevention of work-related decompression illness events by detection of a cardiac
      right-to-left shunt.
AB  - A 44-year-old tunnel worker was studied who suffered from several unexplained
      decompression illness events for almost 15 years. This caisson worker was
      affected after standard pressure profiles that did not cause symptoms of
      decompression illness in his colleagues on the same shift. Transesophageal
      echocardiography revealed an atrial septal defect (grade II) in this otherwise
      healthy man. Cranial magnetic resonance imaging showed ischemic brain lesions.
      Among divers, patent foramen ovale, the most common cause of cardiac right-to
      left shunts, was shown to increase the risk for decompression illness events by a
      factor of 4.5 and to double the risk of ischemic brain lesions. Hyperbaric
      workers with symptoms of unexplained decompression illness, even if they are only
      slight, should immediately be transferred to a cardiologist so that a cardiac
      right-to-left shunt will not be overlooked.

PMID- 15458019
TI  - "You get what you ask for"--impact of the wording of questions on skin disease.

PMID- 15458020
TI  - Ministry leadership development: a new pilgrimage.

PMID- 15458021
TI  - New styles in trustee leadership.

PMID- 15458022
TI  - Against human trafficking. Even health care organizations have been among the
      beneficiaries of this modern form of slavery.

PMID- 15458023
TI  - Diversity is a high priority at CHI.

PMID- 15458024
TI  - What is "leadership formation" now?

PMID- 15458025
TI  - Formation and governance.

PMID- 15458026
TI  - Profiling Catholic health care leaders.

PMID- 15458027
TI  - Health ministry and community.

PMID- 15458028
TI  - Nurturing the ministry's soul.

PMID- 15458029
TI  - A fellowship program for mission leaders.

PMID- 15458030
TI  - Beyond "best intentions".

PMID- 15458031
TI  - Catholic managed care.

PMID- 15458032
TI  - Continuing a community alliance.

PMID- 15458033
TI  - Welcome at EuroRec 2001.

PMID- 15458034
TI  - Interference with the patient-doctor relationship--the cultural gap? Lessons from
      observation.

PMID- 15458035
TI  - Trust me, I'm a patient! The effect of an EHR on my consultation.
AB  - A general assumption has been made within the health care community that the
      introduction of an Electronic Health Record (EHR) is beneficial and improves
      clinical care. However, it is my contention as both a Health Informatician, and
      more importantly a patient, that this assumption is not supported by evidence,
      either scientific or anecdotal. However, to my mind of more importance than this
      is the complete lack of understanding about how using an EHR effects my
      consultation. This paper discusses this issue and identifies four lessons to be
      learned by the EHR community.

PMID- 15458036
TI  - IS4ALL: a working group promoting universal design in Health Telematics.
AB  - In this article, we present an overview of the work being carried out by the EC
      funded project IS4ALL (IST-1999-14101). Specifically, we describe the
      methodological frame of reference, which drives the project's objective to
      introduce universal access principles into the design of Health Telematics
      applications and services. Health Telematics is chosen due to some distinctive
      characteristics, such as the variety of end users involved, the changing
      healthcare contexts of use and the penetration of new computer-mediated
      activities, which re-shape the way in which healthcare practices are structured
      and organized.

PMID- 15458037
TI  - Health information change management lessons--learned from a third of a century
      of change introduction.
AB  - This paper concentrates on the disincentives that discourage particularly doctors
      from readily adopting new health informatics techniques and suggests that health
      project management is a different model of management from that used in other
      industries.

PMID- 15458038
TI  - The Medical Communication and Information System has to be managed by the medical
      profession.

PMID- 15458039
TI  - Secure communication and co-operation of distributed Electronic Patient Records.
AB  - Electronic Health Records (EHR) are moving towards the core application of health
      information systems. Enabling informational interoperability of shared care
      environment including EHR, structure and function of components used have to
      follow open standards and publicly available specifications. This comprises also
      methods and tools applied. Security services needed have to be an integral part
      of architecture and operation of the specified and implemented components.
      Starting with basic architectural paradigms the Magdeburg Medical Informatics
      Department was involved in at the early nineties, the secure behaviour of
      components has been derived. For establishing the required trustworthiness,
      security models have been introduced and presented in the paper. Beside
      communication security services based on standardised Public Key Infrastructure
      (PKI) and security token such as Health Professional Cards (HPC), policy-defined
      application security services such as authorisation, access control,
      accountability, etc., of information recorded, stored and processed must be
      guaranteed. In that context, appropriate resource access decision services have
      to be established. As the HARP project result, a component-based EHR architecture
      has been specified and demonstrated for enforcing fine-grained security services
      by binding certificates to application components, by the way enforcing policies.

PMID- 15458040
TI  - The protection of individuals by protecting medical data in EHRs.
AB  - The paper discusses the changes in the delivery of Healthcare and the ways in
      which individuals need to be protected by protecting their Electronic Health
      Records. A Code of Ethics is needed for health Information Professionals, Data
      Protection and Security issues need to be taken more seriously. Health
      Informatics needs to address the issues of safety in the delivery of Healthcare
      so that it provides solutions to healthcare safety problems rather than
      increasing the problems to be addressed.

PMID- 15458041
TI  - Electronic Health Care Records in Europe: confidentiality issues from an American
      perspective.
AB  - The confidentiality and security issues related to the European Electronic Health
      Care Records have been approached in the United States as well. This paper
      synthesizes several solutions and comments on these issues from the legal
      viewpoint in the United States, as well as some preoccupations of the academic
      world to improve and standardize the quality of the security and confidentiality
      of data from studies involving human subjects.

PMID- 15458042
TI  - Information architecture for a federated health record server.
AB  - This paper describes the information models that have been used to implement a
      federated health record server and to deploy it in a live clinical setting. The
      authors, working at the Centre for Health Informatics and Multiprofessional
      Education (University College London), have built up over a decade of experience
      within Europe on the requirements and information models that are needed to
      underpin comprehensive multi-professional electronic health records. This work
      has involved collaboration with a wide range of health care and informatics
      organisations and partners in the healthcare computing industry across Europe
      though the EU Health Telematics projects GEHR, Synapses, EHCR-SupA, SynEx and
      Medicate. The resulting architecture models have fed into recent European
      standardisation work in this area, such as CEN TC/251 ENV 13606. UCL has
      implemented a federated health record server based on these models which is now
      running in the Department of Cardiovascular Medicine at the Whittington Hospital
      in North London. The information models described in this paper reflect a
      refinement based on this implementation experience.

PMID- 15458043
TI  - Standards supporting interoperability and EHCR communication--a CEN TC251
      perspective.
AB  - This paper has been submitted by Tom Marley. Tom was a member of the project team
      which produced ENV 13606 Part 1: and acted as liaison to the Part 4 project team.
      Tom is currently writing up the document on General Purpose Information
      Components.

PMID- 15458044
TI  - Unified EHR standards--is convergence possible?
AB  - This paper examines the current state of the art in standards for the electronic
      health record (EHR) and messaging, and proposes a theoretical design basis for
      the EHR which is formal yet flexible, and which takes into account many of the
      difficulties experienced in the past. Recommendations are given for how
      convergence of EHR specifications might occur, in order to achieve a unified
      standard suitable for all clinical and cultural contexts.

PMID- 15458045
TI  - Standards in electronic health care records: the EADG/BACH paradigm.

PMID- 15458046
TI  - Sharing clinical information. principles and task-oriented solutions.
AB  - Increasing cooperation among health professionals--within and across
      organizations--require a suitable sharing of clinical information from
      heterogeneous (electronic) documentation. Information originates from healthcare
      activities and may be organized within record systems in relation to health
      issues, episodes of care, episodes of illness, etc. Implementation of record
      systems depends on tasks and attitudes within each particular healthcare
      environment, that determine (i) the balance among functions of the record system,
      e.g. supporting human memory and decision making, supporting workflow management,
      recording circumstances about stored data, (ii) the particular organization of a
      record, (iii) the details of clinical statements that should be explicit or
      understood. In this paper we present a set of features of record systems and of
      their context that affect sharing of clinical information.

PMID- 15458047
TI  - The industrial forum.

PMID- 15458048
TI  - A message model designed by EDISANTE WG 11.
AB  - WG 11 is one of the Working Groups of the EDISANTE Association. First, his
      mission was to define message models with two parts: The envelope of the message,
      including a header, the characteristics of the transmitter, of the receiver, and
      of the patient concerned. The contents of the message, including medical data
      which could be exchanged between different middleware. This second part was
      halted by the " Reseau Sante Social", public network for all the healthcare
      professionals, who want to have a structured content for his "medical message
      format". The prupose of EDISANTE is essentially to promote the use of EDI in
      health care. In a second time, this association decide to include work about
      envelope in a larger domain concerning all exchanges in medical domains, so the
      GT 11 centred his action on content.

PMID- 15458049
TI  - Closing remarks to the EuroRec '01 Working Conference on the Electronic Health
      Record. Aix-en-Provence, November 2001.

PMID- 15458050
TI  - Outcome of EuroRec '01, lessons drawn and farewell!

PMID- 15458051
TI  - The virtualization of medicine: a decade of pitfalls and progress.
AB  - This paper is a personal perspective on VR in medicine over the last decade.

PMID- 15458052
TI  - Moore's Law, disruptive technologies, and the clinician.
AB  - The advancement of technical power described by Moore's Law offers great
      potential for enabling more cost-effective medical devices and systems. However,
      progress has been slow. Many factors for this failure have been cited, including
      the anti-rational economic structure of healthcare and the complexity and long
      time scale of medical development. Christensen et al. suggest that "disruptive
      technologies" may circumvent some of these difficulties. "Disruptive
      Technologies" are defined as those that are established in one market, but then
      penetrate and overwhelm another market. These incursions are accelerated by
      economic factors, and capitalize on functionality, reliability, and advancements
      supported by the original market. Christensen has cited many examples from
      industrial and service businesses, but few examples can be found yet in
      healthcare. We argue that positive technology impacts in medicine occur most
      readily when innovators augment the skills of and collaborate with caregivers,
      rather than seeking to displace them. In the short term, a new approach may
      improve efficiency or quality. In the longer term, such approaches may obviate
      human tasks at lower-skill levels, and even permit task automation. One
      successful example has been the introduction of flexible monitoring for
      physiologic information. Systems for computer-aided diagnosis, which have failed
      to impact complex decision making, have succeeded in simpler specialty areas such
      as the interpretation of EKG's and mammograms, and may do the same with analysis
      of some pathology images. The next frontier may the operating room, and the
      adoption of such systemic technologies by caregivers in emergency medicine and
      general care may then have an even wider "disruptive" effect. Responding to time
      and cost pressures, and the desire to move care to the patient, other workers,
      such as radiologists, will drive the trend away from isolated, complex, large
      scale devices, and toward integrated, modular, and simpler networked
      technologies. In summary, technological "push" will continue in the demanding
      cutting-edge application areas as always, but the "disruption" will occur through
      wider application of lower-cost technologies, pulled by the users. The
      capabilities described by Moore's Law will allow the advancements necessary to
      facilitate this dissemination of capability and its ultimate benefit, so long
      sought.

PMID- 15458053
TI  - Heuristic haptic texture for surgical simulations.
AB  - Generation of credible force feedback renderings adds the sense of touch crucial
      for the development of a realistic virtual surgical environment. However, a
      number of difficulties must be overcome before this can be achieved. One of the
      problems is the paucity of data on the in-vivo tissue compliance properties
      needed to generate acceptable output forces. Without this "haptic texture," the
      sense of touch component remains relatively primitive and unrealistic. Current
      research in the quantitative analysis of biomechanics of living tissue, including
      collection of in-vivo tissue compliance data using specialized sensors, has made
      tremendous progress. However, integration of all facets of biomechanical data in
      order to transfer them into haptic texture remains a very difficult problem. For
      this reason, we are attempting to create a library of heuristic haptic textures
      of anatomical structures. The library of heuristic haptic textures will capture
      the expert's sense of feel for selected anatomical structures and will be used to
      convey the sense of touch for surgical training simulations. Once the techniques
      for converting biomechanical data into haptic texture become more robust, this
      library can be used as a benchmark to verify theoretical computational models
      used for generating output forces in haptic devices.

PMID- 15458054
TI  - Mastoidectomy simulation with combined visual and haptic feedback.
AB  - Mastoidectomy is one of the most common surgical procedures relating to the
      petrous bone. In this paper we describe our preliminary results in the
      realization of a virtual reality mastoidectomy simulator. Our system is designed
      to work on patient-specific volumetric object models directly derived from 3D CT
      and MRI images. The paper summarizes the detailed task analysis performed in
      order to define the system requirements, introduces the architecture of the
      prototype simulator, and discusses the initial feedback received from selected
      end users.

PMID- 15458055
TI  - Tele-Immersive medical educational environment.
AB  - By combining teleconferencing, tele-presence, and Virtual Reality, the Tele
      Immersive environment enables master surgeons to teach residents in remote
      locations. The design and implementation of a Tele-Immersive medical educational
      environment, Teledu, is presented in this paper. Teledu defines a set of Tele
      Immersive user interfaces for medical education. In addition, an Application
      Programming Interface (API) is provided so that developers can easily develop
      different applications with different requirements in this environment. With the
      help of this API, programmers only need to design a plug-in to load their
      application specific data set. The plug-in is an object-oriented data set loader.
      Methods for rendering, handling, and interacting with the data set for each
      application can be programmed in the plug-in. The environment has a teacher mode
      and a student mode. The teacher and the students can interact with the same
      medical models, point, gesture, converse, and see each other.

PMID- 15458056
TI  - An immersive simulation system for provoking and analyzing cataplexy.
AB  - Cataplexy, a sudden loss of voluntary muscle control, is one of the hallmark
      symptoms of narcolepsy, a sleep disorder characterized by excessive daytime
      sleepiness. Cataplexy is usually triggered by strong, spontaneous emotions, such
      as laughter, surprise, fear or anger, and is more common in times of stress. The
      Sleep Disorders Unit and the Biomedical Imaging Resource at Mayo Clinic are
      developing interactive display technology for reliably inducing cataplexy during
      clinical monitoring. The use of immersive displays may help bypass patient
      defenses, and game-like "unreality" allows introduction of surprising,
      threatening, or humorous elements, with little risk of offending patients. The
      project is referred to as the "Cataplexy/Narcolepsy Activation Program", or
      CatNAP. We have developed an automobile driving simulation to allow the
      introduction of humorous, surprising, or stress-inducing events and objects as
      the patient attempts to navigate a simulated vehicle through a virtual town. The
      patient wears a stereoscopic head-mounted display, by which he views the virtual
      town through the windows of his simulated vehicle. The vehicle is controlled via
      a driving simulator steering wheel and pedal cluster. The patient is instructed
      to drive his vehicle to another location in town, given initial directions and
      street signs. As he attempts to accomplish the task, various objects, sounds or
      conditions occur which may distract, startle, frustrate or cause laughter;
      responses which may trigger a cataplectic episode. The patient can be monitored
      by reflex tests and EMG recordings during the driving experience. An evaluation
      phase with volunteer patients previously diagnosed with cataplexy has been
      completed. The goal of these trials was to gain insight from the volunteers as to
      improvements that could be made to the simulation. All patients that participated
      in the evaluation phase have been under a physician's care for a number of years
      and control their cataplexy with medication. We believe this is a novel and
      innovative approach to a difficult problem. CatNAP is a compelling example of the
      potentially effective application of virtual reality technology to an important
      clinical problem that has resisted previous approaches. Preliminary results
      suggest that an immersive simulation system like CatNAP will be able to reliably
      induce cataplexy in a controlled environment. The project is continuing through a
      final stage of refinement prior to conducting a full clinical study.

PMID- 15458057
TI  - Soft-tissue simulation using LEM--Long Elements Method.
AB  - This paper discusses the use of the Long Elements Method--LEM in soft tissue
      modeling and surgery simulation. The LEM is a new method for real time,
      physically based, dynamic simulation of deformable objects, based on a new
      meshing strategy, using long elements. The method uses a combination of static
      (state-less) and dynamic approaches to simulate deformations and dynamics,
      obtaining a higher degree of compliance per time step. Global deformations that
      conserve volume and are convincingly compliant are obtained. Models are defined
      using bulk material properties. Elastic and plastic deformations can be
      simulated. The real time performance of the method and its intrinsic properties
      of volume conservation, modeling based in material properties and simpler meshing
      make it particularly attractive for soft tissue modeling and surgery simulation.

PMID- 15458058
TI  - Self-administered decision support tool for triage: results of a retrospective
      study.
AB  - BACKGROUND: This study was designed to evaluate the safety of a self-administered
      triage tool. MATERIALS: Ninety-five patients older than 14 years who presented to
      Memorial Hermann Hospital emergency room (ER) with chief complaint of abdominal
      pain were included in the study. Their ER disposition and final diagnoses were
      logged into a database. The assigned disposition and top three diagnoses by the
      triage tool for each patient were also logged into the database. An emergency
      physician blinded to the actual disposition reviewed all cases and provided a
      disposition for each patient. RESULTS: The system disposed 51.1% of cases
      appropriately and under-disposed 4.4% of cases. Comparison between the system and
      the emergency physician shows that all cases under-disposed by the system are
      also under-disposed by the physician.

PMID- 15458059
TI  - Calibration and accuracy testing for image-enhanced endoscopy.
AB  - New surgical navigation techniques may combine the use of live video from a
      surgical endoscope with 3D volumetrically-reconstructed images of a patient's
      anatomy. This image-enhanced endoscopy requires calibration of the endoscope to
      ensure that the mapping of the real endoscope image to its virtual counterpart is
      properly performed. The application of a technique to calibrate an endoscope
      prior to use in a diagnostic or therapeutic procedure is described, as well as a
      simple yet effective linear method for lens-distortion compensation. The results
      of accuracy testing of the calibration technique using a dedicated testing
      apparatus are reported.

PMID- 15458060
TI  - Open surgery simulation.
AB  - The design of simulators for surgical training and planning poses a great number
      of technical challenges. Therefore the focus of systems and algorithms was mostly
      on the more restricted minimal invasive surgery. This paper tackles the more
      general problem of open surgery and presents efficient solutions to several of
      the main difficulties. In addition to an improved collision detection scheme for
      computing interactions with even heavily moving tissue, a hierarchical system for
      the haptic rendering has been realized in order to reach the best performance of
      haptic feedback. A flexible way of modeling complex surgical tools out of simple
      basic components is proposed. In order to achieve a realistic and at the same
      time fast relaxation of the tissue, the approach of explicit finite elements has
      been substantially improved. We are able to demonstrate realistic simulations of
      interactive open surgery scenarios.

PMID- 15458061
TI  - Virtual reality-based post-stroke hand rehabilitation.
AB  - A VR-based system using a CyberGlove and a Rutgers Master II-ND haptic glove was
      used to rehabilitate four post-stroke patients in the chronic phase. Each patient
      had to perform a variety of VR exercises to reduce impairments in their finger
      range of motion, speed, fractionation and strength. Patients exercised for about
      two hours per day, five days a week for three weeks. Results showed that three of
      the patients had gains in thumb range (50-140%) and finger speed (10-15%) over
      the three weeks trial. All four patients had significant improvement in finger
      fractionation (40-118%). Gains in finger strength were modest, due in part to an
      unexpected hardware malfunction. Two of the patients were measured against one
      month post intervention and showed good retention. Evaluation using the Jebsen
      Test of Hand Function showed a reduction of 23-28% in time completion for two of
      the patients (the ones with the higher degrees of impairment). A prehension task
      was performed 9-40% faster for three of the patients after the intervention
      illustrating transfer of their improvement to a functional task.

PMID- 15458062
TI  - Computer-controlled motorized endoscopic grasper for in vivo measurement of soft
      tissue biomechanical characteristics.
AB  - Accurate biomechanical characteristics of tissues are essential for developing
      realistic virtual reality surgical simulators utilizing haptic devices. Surgical
      simulation technology has progressed rapidly but without a large database of soft
      tissue mechanical properties with which to incorporate. The device described here
      is a computer-controlled, motorized endoscopic grasper capable of applying
      surgically relevant levels of force to tissue in vivo and measuring the tissue's
      force-deformation properties.

PMID- 15458063
TI  - Generalized interactions using virtual tools within the spring framework:
      probing, piercing, cauterizing and ablating.
AB  - We present schemes for real-time generalized interactions such as probing,
      piercing, cauterizing and ablating virtual tissues. These methods have been
      implemented in a robust, real-time (haptic rate) surgical simulation environment
      allowing us to model procedures including animal dissection, microsurgery,
      hysteroscopy, and cleft lip repair.

PMID- 15458064
TI  - Generalized interactions using virtual tools within the spring framework:
      cutting.
AB  - We present schemes for real-time generalized mesh cutting. Starting with the a
      basic example, we describe the details of implementing cutting on single and
      multiple surface objects as well as hybrid and volumetric meshes using virtual
      tools with single and multiple cutting surfaces. These methods have been
      implemented in a robust surgical simulation environment allowing us to model
      procedures ranging from animal dissection to cleft lip correction.

PMID- 15458065
TI  - Volumetric implant-planning based on Symmetry Considerations.
AB  - Symmetry Considerations can be used not only to plan the desired shape of
      reconstructured bone structures, but also to generate prototypes for soft tissue
      implants. The poster describes a system which allows to calculate a symmetry
      plane in the facial area automatically and computes proposals for implants or
      transplants. The system presented has been used to calculate soft tissue implants
      and a replacement for parts of the lower jaw.

PMID- 15458066
TI  - Clinical test for Attention Enhancement System.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) is a childhood syndrome
      characterized by short attention span, impulsiveness, and hyperactivity, which
      often leads to learning disabilities and various behavioral problems. The
      prevalence rates for ADHD varied from a low of 2.0% to a high of 6.3% in 1992
      statistics, and it may be higher now. Using Virtual Environments and
      Neurofeedback, we have developed an Attention Enhancement System for treating
      ADHD. And we made a clinical test. Classroom-based virtual environments are
      constructed for intimacy and intensive attention enhancement. In this basic
      virtual environment, subjects performed some training sessions. There are two
      kinds of training sessions. One is Virtual Reality Cognitive Training (VRCT) and
      the other is Virtual Reality Neurofeedback Training (VRNT). In VRNT, we made a
      change in the virtual environment by Neurofeedback. Namely, if the Beta ratio is
      greater than the specified threshold level, the change as positive reinforce is
      created in the virtual environment. 50 subjects, aged 14 to 18, who had committed
      crimes and had been isolated in a reformatory took part in this study. They were
      randomly assigned to one of five 10-subject groups: a control Group, two placebo
      groups, and two experimental groups. The experimental groups and the placebo
      groups underwent 10 sessions over two weeks. The control group underwent no
      training session during the same period of time. While the experimental groups
      used HMD and Head Tracker in each session, the placebo groups used only a
      computer monitor. Consequently, only the experimental Groups could look around
      the virtual classroom. Besides that, Placebo Group 1 and Experimental Group 1
      performed the same task(Neurofeedback Training), and Placebo Group 2 and
      Experimental Group 2 also performed the same task(Cognitive Training). All
      subjects Continuous Performance Task(CPT) before and after all training sessions.
      In the number of correct answers, omission errors and signal detection index
      (d'), the subjects' scores from CPT showed significant improvement (p<0.01) after
      all of the training sessions, while control group indicated no significant
      change. And experimental groups showed significant difference (p<0.01) with
      placebo groups. Lastly, the Virtual Reality Neurofeedback training group and the
      Virtual Reality Cognitive training group indicated not significant difference.
      Our System is supposed to enhance subjects' attention and lead their behavioral
      improvement. And also, we can conclude that virtual reality training (both
      Neurofeedback training and Cognitive training) has an advantage for attention
      enhancement compared with desk-top training.

PMID- 15458067
TI  - Training and pretreatment planning of interventional neuroradiology procedures-
      initial clinical validation.
AB  - A PC based system for simulating image-guided interventional neuroradiological
      procedures for physician training and patient specific pretreatment planning is
      described. The system allows physicians to manipulate and interface
      interventional devices such as catheters, guidewires, stents and coils within 2-D
      and hybrid surface and volume rendered 3-D patient vascular images in real time.
      A finite element method is employed to model the interaction of the catheters and
      guidewires with the vascular system. Fluoroscopic, roadmapping and volume
      rendered 3-D presentations of the vasculature are provided. System software
      libraries allow for the use of commonly employed catheters, guidewires, stents
      and occluding coils of various shapes and sizes. The results of an initial
      clinical validation suggest that the experience gained from our simulator is
      comparable with that of using a vascular phantom. We are conducting further
      validation with the aim of providing patient specific pretreatment planning.

PMID- 15458068
TI  - Navigation by walking around: using the Pressure Mat to move in virtual worlds.
AB  - This paper describes a new virtual reality (VR) locomotion input device, the
      Pressure Mat, which allows a simulator user to navigate/traverse a virtual
      environment (VE) using similar motions as in the real world; i.e., walk, run,
      crawl. The device consists of an array of pressure sensitive resistors covered by
      a thin, flexible mat. The resistor array is connected to a personal computer (PC)
      that uses a real-time pattern recognition algorithm to determine if the user is
      standing still, or walking forward, backward, left or right. The information from
      the Pressure Mat was used to allow users to navigate in a VE. The Pressure Mat
      may also be useful in the diagnosis of a variety of conditions and/or in
      rehabilitative therapy.

PMID- 15458069
TI  - Intraoperative guidance of pre-planned bone deformations with a surface scanning
      system.
AB  - Computer- and robot-based systems to support interventions become more and more
      important in modem surgery. In general these systems provide methods to plan an
      intervention pre-operatively and to execute it with support from a autonomous
      robot-system. Due to the principle restriction of a robot to comparatively simple
      work steps, there are some complex work steps which the surgeon may plan but
      which he/she has to execute manually. In craniofacial surgery osteotomised bone
      segments are deformed by hand to a shape given by the planning system. We support
      the execution of pre-planned deformation by comparison of the actual shape of an
      object with the target shape. The actual shape is obtained intra-operatively with
      a surface scanning device, the deviation from the target shape are visualised by
      projecting colour-coded error values directly on the object to be deformed. The
      surgeon uses these projections to adjust further deformation steps. The system is
      therefore able to validate the correct execution of planned deformations,
      especially of bony structures.

PMID- 15458070
TI  - Creating a statistical atlas of the cranium.
AB  - Normative data is very important for simulation procedures in craniofacial
      surgery. While treating e.g. a malformed skull the surgeon seeks to reconstruct
      its natural and harmonic shape. Atlas or normative data of the skull could
      support the surgeon in this effort, as it would provide a standard model of the
      skull which gives an idea of the natural shape. We create a standard skull by
      averaging regularly formed skulls in a shape space spanned by spherical
      harmonics. While state-of-the-art methods use landmarks to define the shape and
      mean shapes, this method is deterministic, i.e. it manages averaging without
      landmarks and it provides a complete description of the shape. In addition the
      shape space can be used to classify shapes to identify different types of an
      anatomy.

PMID- 15458071
TI  - Augmented reality and training for airway management procedures.
AB  - Augmented reality is often used for interactive, three-dimensional visualization
      within the medical community. To this end, we present the integration of an
      augmented reality system that will be used to train military medics in airway
      management. The system demonstrates how a head-mounted projective display can be
      integrated with a desktop PC to create an augmented reality visualization.
      Furthermore, the system, which uses a lightweight optical tracker, demonstrates
      the low cost and the portability of the application.

PMID- 15458072
TI  - Multimodal simulation of laparoscopic Heller myotomy using a meshless technique.
AB  - In this work we focus our attention on developing a surgical simulator for
      performing laparoscopic Heller myotomy using force feedback. A meshless numerical
      technique, the method of finite spheres, is used for the purpose of physically
      based, real time haptic and graphical rendering of soft tissues. Localized
      discretization allows display of deformations in the vicinity of the tool tip as
      well as interaction forces at high update rates (kHz). Novel cutting algorithms
      are implemented using point-based representation of anatomical models. Graphical
      rendering is accomplished by using a recently developed volumetric rendering
      technique known as splatting.

PMID- 15458073
TI  - Imaging and visualization of pathology beneath the retinal surface.
AB  - Pathology beneath the highly reflective surface, such as the human retina, is key
      in the detection and management of disease. Advanced imaging techniques can help
      reveal these. Visualization and guiding the imaging to the appropriate area still
      remain as problems, in part due to the small scale of the pathology with respect
      to the potential area to be covered.

PMID- 15458074
TI  - 'Putting it on the table': direct-manipulative interaction and multi-user display
      technologies for semi-immersive environments and augmented reality applications.
AB  - Collaborative virtual environments for diagnosis and treatment planning are
      increasingly gaining importance in our global society. Virtual and Augmented
      Reality approaches promised to provide valuable means for the involved
      interactive data analysis, but the underlying technologies still create a
      cumbersome work environment that is inadequate for clinical employment. This
      paper addresses two of the shortcomings of such technology: Intuitive interaction
      with multi-dimensional data in immersive and semi-immersive environments as well
      as stereoscopic multi-user displays combining the advantages of Virtual and
      Augmented Reality technology.

PMID- 15458075
TI  - Quantitative image analysis of the cartilage in Virtual Reality.
AB  - The objective of this work is to develop image processing methods for analysing
      the morphology of the joint cartilage with magnetic resonance imaging.
      Quantitative data on the morphological distribution of the joint cartilage are of
      great interest for both research as well as for diagnosis. The cartilage
      thickness provides information on the local cartilage occurance and may therefore
      be helpful in early and objective diagnosing degenerative cartilage changes,
      monitoring the pathogenesis of osteoarthritis, and controlling the success of
      chondroprotective treatment. In biomechanics, the thickness distribution serves
      to analyse the functional adaptation or the compression of the cartilage under
      loading and may be used for numerical simulation of load transmission in the
      joint.

PMID- 15458076
TI  - Using mixed reality, force feedback and tactile augmentation to improve the
      realism of medical simulation.
AB  - This paper describes an application of a display approach which uses chromakey
      techniques to composite real and computer-generated images allowing a user to see
      his hands and medical instruments collocated with the display of virtual objects
      during a medical training simulation. Haptic feedback is provided through the use
      of a PHANTOM force feedback device in addition to tactile augmentation, which
      allows the user to touch virtual objects by introducing corresponding real
      objects in the workspace. A simplified catheter introducer insertion simulation
      was developed to demonstrate the capabilities of this approach.

PMID- 15458077
TI  - Wireless live streaming video of laparoscopic surgery: a bandwidth analysis for
      handheld computers.
AB  - Over the last six years, streaming media has emerged as a powerful tool for
      delivering multimedia content over networks. Concurrently, wireless technology
      has evolved, freeing users from desktop boundaries and wired infrastructures. At
      the University of Kentucky Medical Center, we have integrated these technologies
      to develop a system that can wirelessly transmit live surgery from the operating
      room to a handheld computer. This study establishes the feasibility of using our
      system to view surgeries and describes the effect of bandwidth on image quality.
      A live laparoscopic ventral hernia repair was transmitted to a single handheld
      computer using five encoding speeds at a constant frame rate, and the quality of
      the resulting streaming images was evaluated. No video images were rendered when
      video data were encoded at 28.8 kilobytes per second (Kbps), the slowest encoding
      bitrate studied. The highest quality images were rendered at encoding speeds
      greater than or equal to 150 Kbps. Of note, a 15 second transmission delay was
      experienced using all four encoding schemes that rendered video images. We
      believe that the wireless transmission of streaming video to handheld computers
      has tremendous potential to enhance surgical education. For medical students and
      residents, the ability to view live surgeries, lectures, courses and seminars on
      handheld computers means a larger number of learning opportunities. In addition,
      we envision that wireless enabled devices may be used to telemonitor surgical
      procedures. However, bandwidth availability and streaming delay are major issues
      that must be addressed before wireless telementoring becomes a reality.

PMID- 15458078
TI  - Using semi-automated image processing and desktop systems to incorporate actual
      patient volumetric data in immersive surgical planning and viewing systems for
      multiple patients.
AB  - This paper describes how patient specific volumetric data are managed from image
      acquisition through final processing for the purposes of creating a 3D VR
      rendering of user selected and manipulated 3D models. The system described here
      allows for the development of quick, inexpensive, and clinician manipulated
      patient-specific models. The utility of this process is demonstrated by being
      able to move VRML models to desktop or immersive environments for both pre
      operative planning and patient-specific surgical and anatomical training.

PMID- 15458079
TI  - Interactive simulation of the teeth cleaning process using volumetric prototypes.
AB  - In this paper, an interactive simulation system for teeth cleaning is presented.
      This simulation system offers assistance for optimizing design and manufacturing
      of new toothbrushes. Data acquisition and pre-processing techniques for the model
      generation are shown and the mathematical method for modelling of the elastic
      behaviour of the toothbrushes parts is explained. Afterwards, a new approach to
      collision detection based on simple volumetric prototypes is described, user
      interaction is discussed and results of the project are shown.

PMID- 15458080
TI  - A haptic virtual environment for tele-echography.
AB  - Having a haptic virtual environment for tele-echography will enable the medical
      expert with faster adaptation and especially facilitated immersion in what we
      could call a "virtual echographic examination cabinet". The innovation of this
      haptic control is to preserve medical expert proprioception and gesture feelings,
      which provide the users with indications that are synchronized with the
      echographic images. In this paper, we will focus on the telegesture module: we
      will detail several issues and solutions related to this particular problem of
      tele-robotic scan examination.

PMID- 15458081
TI  - Cryotherapy simulator for localized prostate cancer.
AB  - Cryotherapy is a treatment modality that uses a technique to selectively freeze
      tissue and thereby cause controlled tissue destruction. The procedure involves
      placement of multiple small diameter probes through the perineum into the
      prostate tissue at selected spatial intervals. Transrectal ultrasound is used to
      properly position the cylindrical probes before activation of the liquid Argon
      cooling element, which lowers the tissue temperature below -40 degrees
      Centigrade. Tissue effect is monitored by transrectal ultrasound changes as well
      as thermocouples placed in the tissue. The computer-based cryotherapy simulation
      system mimics the major surgical steps involved in the procedure. The simulated
      real-time ultrasound display is generated from 3-D ultrasound datasets where the
      interaction of the ultrasound with the instruments as well as the frozen tissue
      is simulated by image processing. The thermal and mechanical simulations of the
      tissue are done using a modified finite-difference/finite-element method
      optimized for real-time performance. The simulator developed is a part of a
      comprehensive training program, including a computer-based learning system and
      hands-on training program with a proctor, designed to familiarize the physician
      with the technique and equipment involved.

PMID- 15458082
TI  - Reliability and validity of Endotower, a virtual reality trainer for angled
      endoscope navigation.
AB  - We hypothesized that a simulator designed to train surgical novices angled
      laparoscopic navigation would show an improvement in subjects' performance, a
      high test re-test reliability and high internal validity as measured by
      standardized coefficient alpha. It was also predicted that simulator performance
      would be strongly related to objectively assess perceptual and visuospatial
      ability. EndoTower has good face validity in that it mimics precisely the
      performance of an angled laparoscope and previous studies suggest construct
      validity. In this study, EndoTower is shown to be a trainer intended for
      laparoscopic skill than can test for inherent perceptual and visuospatial
      ability.

PMID- 15458083
TI  - Volumetric virtual body structures.
AB  - Understanding the visuospatial aspects of anatomic structures is one of the most
      important goals of gross anatomy. Creation of realistic three-dimensional
      structures of human anatomy has thus been a goal of medical doctors and computer
      scientists. In this paper, we describe a PC/NT based system in which a user can
      easily select anatomical structures to be created, along with the chosen
      connected structures. The system then constructs a three-dimensional volumetric
      model, a virtual body structure, slice-by-slide. Once the virtual structure is
      assembled it is possible to "walk" through the volume with coronal, sagittal, and
      transverse views, or at any angle. The dynamic nature of the system is unique in
      that it allows for real time choice of volumetric body structures to be created,
      their rapid generation, and the ability to manipulate the resulting
      visualization.

PMID- 15458084
TI  - Intraoperative 3D shape recovery of abdominal organs for laparoscopic data
      fusion.
AB  - Precise measurements of geometry should accompany robotic equipments in operating
      rooms if their advantages are further pursued. For deforming organs including the
      liver, intraoperative geometric measurements play an essential role in computer
      surgery in addition to pre-operative geometric information from CT/MRI. The laser
      scan endoscope system acquires and visualizes the shape of the area of interest
      in a flash of time. Results of in-vivo experiments on the liver of a pig verify
      the effectiveness of the proposed system. In the next stage, we aim to make a
      data-fusion in laparoscopy.

PMID- 15458085
TI  - Improved haptic rendering of anatomical data.
AB  - We perform haptic rendering of a polygonal mesh at a high speed, independent of
      its face count, using a topologically structured data representation that avoids
      edge gap effects from small numerical errors. Constraints on the virtual proxy's
      position on the mesh give good results in rendering concave edges. The algorithm
      allows force shading and smoothing at convex corners and edges by an approach
      originally developed for graphic rendering.

PMID- 15458086
TI  - Atlas-based segmentation of pathological knee joints.
AB  - Efficiency, comparability and simplicity are key aspects for user acceptance of
      surgical planning systems in the long term. Automatic segmentation and
      identification of geometric reference systems of the anatomical structures are
      essential to fulfill these requirements. A statistical motivated shape atlas of
      the knee joint, based on 235 normal and abnormal MR and CT volume sets, is
      constructed for automatic segmentation of CT image data. In the first step of the
      atlas construction, the bony structures of the knee were segmented semi
      automatically and processed into a dense and a sparse triangulated surface mesh
      to obtain training data sets. To establish an inter-individual correspondence, a
      skeleton-based registration method is used. The registered sparse surface meshes
      are retriangulated to estimate a pointwise inter-individual correspondence. The
      shape atlas is build upon these correspondences and integrated into a
      segmentation algorithm. An iterative segmentation scheme is proposed, which
      consists of a combination of the iterative-closest-point algorithm for spatial
      registration and of a downhill-simplex optimization procedure for deformation of
      the statistical motivated shape atlas to the image data. We expect the
      statistical shape model to be a robust and image modality independent method for
      the segmentation of pathological knee joints in CT image data.

PMID- 15458087
TI  - A new, accurate and easy to implement camera and video projector model.
AB  - In 2000, the Institute for Process Control and Robotics/Universitat Karlsruhe
      (TH) has developed a prototype system for projector based augmented reality
      consisting of a state-of-the-art PC, two CCD cameras and a video projector which
      is used for registration and projection of surgical planning data. Tracking,
      registration as well as projection require an accurate calibration process for
      cameras and video projectors. We have developed a new, flexible, plain and easy
      to implement model, which can both be used for calibration of cameras and video
      projectors.

PMID- 15458088
TI  - An investigation of immersiveness in virtual reality exposure using physiological
      data.
AB  - As virtual reality technology is increasingly attracting significant attention in
      clinical psychology, especially in the treatment of phobias, physiological
      monitoring is increasingly considered as an objective measuring tool for studying
      participants. However, there are few studies of the normal individual's
      physiological response to virtual environments, or their reactions to different
      virtual environments. The goal of this study is to analyze non-phobic
      participants' physiological reaction to two virtual environments: driving and
      flying and to investigate the usefulness of heart rate variability. Eleven non
      phobic participants were exposed to each virtual environment for 15 minutes.
      Heart rate, skin resistance, and skin temperature measurements were taken for
      physiological monitoring and Presence and Simulator Sickness Questionnaires were
      obtained after each exposure. This study found that skin resistance and heart
      rate variability can be used to show arousal of participant exposed to virtual
      environments experience and that such measures generally returned to normal as
      time went by. The Study showed that skin resistance and heart rate can be used as
      objective measures in monitoring the reaction of non-phobic participants to
      virtual environments. Significantly, heart rate variability analysis in virtual
      environments showed that it could be useful for assessing the emotional states of
      participants.

PMID- 15458089
TI  - Using stereoscopy for medical virtual reality.
AB  - The use of stereoscopy to enhance the immersive experience obtained from a
      virtual environment is well known, and many medical applications can benefit from
      this technology. The stereoscopic projection sessions at the last two MMVR
      conferences contain many excellent examples. Stereoscopy need not be expensive to
      implement, and can easily be provided on a desktop PC. This paper looks at the
      different options available today, from active stereo, to passive stereo, to
      autostereoscopic displays, and their deployment on both high-end and low-end
      systems. The potential benefits of these different approaches are illustrated
      with examples from medical visualisation projects currently being carried out at
      the Manchester Visualization Centre (MVC).

PMID- 15458090
TI  - A virtual environment for esophageal intubation training.
AB  - Esophageal intubations are performed for urgent airway control in injured
      patients. Current methods of training include working on cadavers and mannequins,
      which lack the realism of a living human being. Work in this field has been
      limited due to the complex nature of simulating in real-time the interactive
      forces and deformations which occur during an actual patient intubation. This
      study addressed the issue of intubation training in an attempt to bridge the gap
      between actual and virtual patient scenarios. The two haptic devices along with
      the real-time performance of the simulator give it both visual and physical
      realism. The three dimensional viewing and interaction available through virtual
      reality make it possible for physicians, pre-hospital personnel and students to
      practice many esophageal intubations without ever touching a patient. The ability
      for a medical professional to practice a procedure multiple times prior to
      performing it on a patient will both enhance the skill of the individual while
      reducing the risk to the patient.

PMID- 15458091
TI  - Visible Korean Human: another trial for making serially-sectioned images.
AB  - In this ongoing study, we are trying to make Visible Korean Human (Mar 2000--Feb
      2005). The complete MRIs and CTs of the Korean cadaver's entire body are scanned.
      The cadaver is serially-sectioned at 0.2 mm thickness without any missing images.
      The anatomical structures in the sectioned images are segmented. The Visible
      Korean Human is expected to be more helpful than Visible Human in the following
      ways. First, the Korean data will be more helpful in diagnosing and treating the
      patients belonging to the yellow race. Second, MRIs and CTs of the entire body at
      1 mm thickness will be more helpful in studying the MRIs and CTs. Third,
      sectioned images without any missing images will be more helpful in making the
      complete 3D images. Fifth, small pixel size (0.2 mm x 0.2 mm) and thin thickness
      (0.2 mm) of sectioned images will be more helpful in showing the small anatomical
      structures greater than 0.2 mm. Sixth, the additional segmented images will be
      more helpful in making the 3D image and virtual dissection software. The Visible
      Korean Human will be the basis for making better 3D image and virtual dissection
      software which will be more helpful in medical education.

PMID- 15458092
TI  - High performance bilateral telerobot control.
AB  - Telerobotic systems are used when the environment that requires manipulation is
      not easily accessible to humans, as in space, remote, hazardous, or microscopic
      applications or to extend the capabilities of an operator by scaling motions and
      forces. The Creare control algorithm and software is an enabling technology that
      makes possible guaranteed stability and high performance for force-feedback
      telerobots. We have developed the necessary theory, structure, and software
      design required to implement high performance telerobot systems with time delay.
      This includes controllers for the master and slave manipulators, the manipulator
      servo levels, the communication link, and impedance shaping modules. We verified
      the performance using both bench top hardware as well as a commercial
      microsurgery system.

PMID- 15458093
TI  - Daily patient set-up control in radiation therapy by coded light projection.
AB  - Advances in conformal radiation therapy to control disease via dose escalation
      are challenged by set-up uncertainties. Recently, techniques have been developed
      to use surface features to evaluate the patient's position and correct it where
      necessary. The aim of this study was to use the patient's surface as a tool for
      daily set-up control and monitoring. We use a surface scanner based on the
      projection of coded light to receive--in a daily routine--a large amount of
      surface points which enables us to register the CT-based planning data with the
      patients current position. By superimposing current and planned volumes, a volume
      of congruency was obtained. An error below 1 mm was considered acceptable. In
      cases where set-up was not satisfactory a map of the surface comparison was
      evaluated showing the areas of missing alignment. According to this information a
      manual repositioning was performed. This procedure was repeated until the error
      was acceptable. No more then 3 repetitions where necessary to obtain an
      acceptable result. The whole procedure including registration, calculation and
      visualization took about 20 sec for one repetition. The use of structured light
      projection in the daily set-up control and monitoring proved to be a noninvasive,
      easy, quick, inexpensive and reliable solution.

PMID- 15458094
TI  - The development and clinical trial of a Driving Simulator for the handicapped.
AB  - We developed a Virtual Reality Driving Simulator in order to safely evaluate and
      improve the driving ability of the handicapped. The Virtual Environment consists
      of 18 sections (e.g. a speed limited road, a strait road, a curved road, a left
      turn course, etc) and each section is linked naturally. For the interface of our
      driving simulator, an actual car was adapted for realism and then connected to a
      computer. We also equipped it with hand control driving devices especially
      adapted for the handicapped. A beam projector was used so that the subjects could
      see the virtual scene on a large screen which was set in front of them. The
      subjects selected for this trial were 10 normal drivers with valid driving
      licenses and 15 patients with thoracicor lumber cord injuries who had prior
      driving experience. For evaluation, 5 driving skills were measured including
      average speed, steering stability, centerline violations, traffic signal
      violations, and driving time in various road conditions such as strait and curved
      roads. The normal subjects manipulated the gas pedal and the brake with their
      feet while the patients manipulated a hand control with their hands. After they
      finished driving the whole course, the participants answered the questions such
      as "How realistic did the Virtual Reality Driving Simulator seeme to you?" and
      "How much was your fear reduced". The five driving skills measured between the
      two groups (normal vs. handicapped) did not show any significant differences (p >
      0.05). And in the three kinds of road conditions (a speed limited road and roads
      with a sharp curve and left-hand turn), the average speed of the handicapped
      group was 45.6 Km, less than 61.2 Km (p<0.05) of the normal group. In all, 11
      patients (73%) reported that their fear of driving was reduced. Furthermore,
      their average score on the degree of realism question was 51.5%.

PMID- 15458095
TI  - Realtime textured 3D-models for medical applications.
AB  - Realistic visualisation becomes more and more important in medicine. Whenever a
      patient individual 3D-model was generated the aim is to visualise the model as
      realistic as possible. We use 3D-models in our diagnostic and therapeutic tools
      for intraoperative visualisation of e.g. CT-scans. Most medical tools uses
      surface-rendering or volume-rendering for virtual visualisation. The coloration
      of a visualised model is normally done by using a convenient colour for each
      surface resp. volume. Our approach for 3D-models generated from motion in image
      series (e.g. videoendoscopes) is to add textures to the 3D-model. The main
      problem is, to handle the huge amount of videoimage-data (20Mb/sec.) and render
      the model in realtime.

PMID- 15458096
TI  - 3D structure from endoscopic images.
AB  - Endoscopy is an important procedure for the diagnostic and therapy of various
      pathologies. In 2000, the Institute for Process Control and Robotics/Universitat
      Karlsruhe (TH) has developed a basic framework for reconstructing 3D models from
      image sequences. The framework is able to realise automatic navigation for new
      colonoscopes with own driving system and on the other hand to offer a virtual 3D
      endoscopic view during bad visibility conditions caused by e.g. abrupt bleeding.
      This method generates a 3D-model intraoperatively compared to preoperatively
      generated 3D-models in virtual endoscopy.

PMID- 15458097
TI  - Visualization and attributation of vascular structures for diagnostics and
      therapy planning.
AB  - In various medical fields vascular structures have to be examined with usually
      two-dimensional views which present imaging techniques produce. The
      interpretation of the data can be supported by 3-dimensional visualization
      techniques. The further analysis requires often the attributation of the
      particular functional or anatomical entities. To attribute these interactively we
      developed two different visualization strategies. In the first one the shape of
      the structures is modelled with OpenGL achieving very fast response times, most
      notably during the navigation. The second strategy, the direct rendering of the
      volume, benefits from the accurate reproduction of the vascular structures.
      Although the rendering needs much more time, the strategy provides similar
      response times for the attributation. Thus, the strategies complement one
      another.

PMID- 15458098
TI  - Development of a virtual speaking simulator using Image Based Rendering.
AB  - The fear of speaking is often cited as the world's most common social phobia. The
      rapid growth of computer technology has enabled the use of virtual reality (VR)
      for the treatment of the fear of public speaking. There are two techniques for
      building virtual environments for the treatment of this fear: a model-based and a
      movie-based method. Both methods have the weakness that they are unrealistic and
      not controllable individually. To understand these disadvantages, this paper
      presents a virtual environment produced with Image Based Rendering (IBR) and a
      chroma-key simultaneously. IBR enables the creation of realistic virtual
      environments where the images are stitched panoramically with the photos taken
      from a digital camera. And the use of chroma-keys puts virtual audience members
      under individual control in the environment. In addition, real time capture
      technique is used in constructing the virtual environments enabling spoken
      interaction between the subject and a therapist or another subject.

PMID- 15458099
TI  - Real-time soft tissue modelling for web-based surgical simulation:
      SurfaceChainMail.
AB  - The Web provides a useful environment for simple surgical training simulations. A
      combination of VRML for 3D rendering, and Java code for the simulation engine,
      has been used for a range of simple neurosurgical demonstrators. However the
      elements in these simulators are rigid, to avoid the computational complexity of
      deformable modelling. In this paper we describe a variation of the ChainMail
      technique that allows us to provide real-time deformable modelling, even in a Web
      browser environment on a PC. Our new algorithm, SurfaceChainMail, has been used
      to develop a simulator for the cutting of two layers of tissue, and separating
      the layers by pulling them apart.

PMID- 15458100
TI  - Virtual food in virtual environments for the treatment of eating disorders.
AB  - Eating disorders (Eds) are one of the problems with higher social repercussion in
      the last years. Sometimes, these clinical syndromes, which are characterized by
      an altered eating behavior, can have dramatic consequences. In eating disorders,
      one of the more critical situations, in addition to other of equal or more
      importance, is the patient's confrontation with food: the visual confrontation,
      the eating process and the repercussion on his weight. Virtual Reality (VR)
      technology has been used in psychology, as a therapeutic help tool for the
      treatment of different psychological problems, for several years now. Their
      helpfulness is increasingly being recognized. Some developed virtual environments
      (VE) and their corresponding published studies endorse the efficiency of this
      tool. Nevertheless, in order to increase the possibilities of success, it is very
      important to obtain a complete patient immersion in the VE: visual, auditory and
      interactive. Sometimes there are processes or actions of reality, which are
      difficult to simulate virtually, and simulating them coarsely would result in the
      patient lack of immersion in the VE, thus seriously decreasing the possibilities
      of success. The eating process is an example, since it consists of several steps,
      some of which (biting, chewing, etc.) don't have an evident virtual solution.
      This article shows how food and eating process have been simulated virtually in
      the development of a virtual environment for the treatment of eating disorders.

PMID- 15458101
TI  - Advancements in immersive VR as a tool for preoperative planning for laparoscopic
      surgery.
AB  - The utility of three-dimensional (3D) models for planning laparoscopic surgery
      and surgical training has been demonstrated. (1) Computed tomography (CT) scans
      with oral and intravenous contrast medium are frequently used for preoperative
      evaluation of patients undergoing complex laparoscopic surgery. Immersive 3D VR
      overcomes many of the conceptual limitations encountered when conveying or
      teaching 3D relationships via 2D images traditionally produced by these scans.
      Over the past year we have made advancements in several areas. First, we have
      improved the quality of our datasets by utilizing higher resolution multi
      detector scans and altering the protocols used. Second, we now register multiple
      isosurface views with standard axial views and volume textured views to provide
      additional information and perspective. Third, we now routinely use auto
      segmentation techniques to visualize individual structures.

PMID- 15458102
TI  - Quantitative methodology of evaluating surgeon performance in laparoscopic
      surgery.
AB  - Quantitative performance and skill assessments are critical for evaluating the
      progress of surgical residents and the efficacy of different training programs.
      Current evaluation methods are subjective and potentially unreliable, so there is
      a need for objective methods to evaluate surgical performance. We identify a
      feasible method to measure kinematic data in the live operating room setting and
      to assess the repeatability of an analysis method based on a hierarchical
      decomposition of surgical tasks. We used an optoelectronic motion analysis system
      to acquire postural data and tool tip trajectories of one expert surgeon over a
      period of four months. To assess repeatability of performance measures, we
      created a hierarchical decomposition diagram describing the procedure in terms of
      surgical tasks, tool sequences and fundamental tool actions. From the kinematic
      data, we extracted characteristic measures of individual tool actions and
      compared these measured distributions using the Kolmogorov-Smirnov statistic. The
      comparisons of distributions show consistent performance over time by a trained
      surgeon and little effect from patient variability, and so are likely reliable
      measures of performance. An expanded set of reliable kinematic measures will form
      the basis for quantifying surgical skill and should be useful in validating
      surgical simulations for use in training, certifying surgeons and designing and
      evaluating new surgical tools.

PMID- 15458103
TI  - Anesthesiology Point of Care project.
AB  - We are developing a dynamic prototype visual communication system for the
      operating room environs. This has classically been viewed as an isolated and
      impenetrable workplace. All medical experiences and all teaching remain in a one
      to one closed loop with no recall or subsequent sharing for the training and
      education of other colleagues. The "Anesthesia Point of Care" (APOC) concept
      embraces the sharing of, recording of, and presentation of various physiological
      and pharmacological events so that real time memory can be shared at a later time
      for the edification of other colleagues who were not present at the time of the
      primary learning event. In addition it also provides a remarkably rapid tool for
      fellow faculty to respond to obvious stress and crisis events that can be
      broadcast instantly at the time of happening. Finally, it also serves as an
      efficient and effective means of paging and general communication throughout the
      daily routines among various healthcare providers in anesthesiology who work as a
      team unit; these include the staff, residents, CRNAs, physician assistants, and
      technicians. This system offers a unique opportunity to eventually develop future
      advanced ideas that can include training exercises, presurgical evaluations,
      surgical scheduling and improvements in efficiency based upon earlier than
      expected case completion or conversely later than expected case completion and
      even as a unique window to development of improved billing itemization and
      coordination.

PMID- 15458104
TI  - CT, MRI and video based analysis of knee kinematics--a basis for CT based
      simulation.
AB  - With the new computer aided surgery techniques a surgery can be split in two
      phases, which are pre-operative planning and intervention. The planning is
      frequently based on three dimensional image data and takes place in the office of
      the surgeon. Using this approach the surgical feeling, the physical feedback of
      the patient, is not available during the planning phase. However, this feedback
      yields information, which is helpful or necessary for the planning. This lack of
      information can be compensated by a simulation module, which simulates kinematic
      data from image volume data. To develop such a module first both image volume
      data and kinematic data have to be captured from a wide range of patients. In
      this work a new approach for kinematic analysis of the knee is presented which
      yields an accuracy which is necessary for such simulation. Because the analysis
      has to be done for many patients the degree of invasiveness is emphasized. This
      contactless and non invasive approach is based on external fixations, anatomical
      skin markers, video sequences and computer tomograms. Position tracking of femur
      and tibia for any motion pattern is possible. Because the individual anatomic
      structures extracted from the tomogram are tracked, an analysis of any point or
      coordinate system can be done later using the originally captured data. This
      gives a new degree of freedom for analysis.

PMID- 15458105
TI  - Spring: a general framework for collaborative, real-time surgical simulation.
AB  - We describe the implementation details of a real-time surgical simulation system
      with soft-tissue modeling and multi-user, multi-instrument, networked haptics.
      The simulator is cross-platform and runs on various Unix and Windows platforms.
      It is written in C++ with OpenGL for graphics; GLUT, GLUI, and MUI for user
      interface; and supports parallel processing. It allows for the relatively easy
      introduction of patient-specific anatomy and supports many common file formats.
      It performs soft-tissue modeling, some limited rigid-body dynamics, and suture
      modeling. The simulator interfaces to many different interaction devices and
      provides for multi-user, multi-instrument collaboration over the Internet. Many
      virtual tools have been created and their interactions with tissue have been
      implemented. In addition, a number of extra features, such as voice input/output,
      real-time texture-mapped video input, stereo and head-mounted display support,
      and replicated display facilities are presented.

PMID- 15458106
TI  - Objective surgical performance evaluation based on haptic feedback.
AB  - In order to develop effective virtual reality training systems for surgery there
      is a need to provide appropriate sensory and performance feedback to the user.
      This paper aims to demonstrate a method by which performance data can be
      collected. This is used to investigate the effect of haptic feedback on
      performance. A PHANTOM desktop device was used in conjunction with a suturing
      simulation A pair of needle-holders was instrumented with strain gauges and
      attached to the stylus of the PHANTOM allowing the measurement of force
      application and time. Suturing performance was evaluated in terms of stitch
      completion time, peak force application, and the length and straightness of the
      stitch. The effect of the level of force feedback provided by the simulation and
      performance over time was considered. The results indicate that the presence of
      force feedback affected task completion time, peak force application and the
      straightness of the stitch. Task completion time was shown to increase with the
      level of force feedback provided. Performance was seen to improve over time in
      terms of task completion time and the accuracy ofthe stitch. The work has
      examined how the presence and level of force feedback affects performance of a
      simple task. The accuracy of haptic feedback is important in the design of
      surgical simulation systems to ensure effective training transfer. A data
      collection method by which objective performance evaluation can be made is
      demonstrated. The method can be applied to training using bench models,
      simulations and potentially in the operating theatre.

PMID- 15458107
TI  - Nasal airflow diagnosis--comparison of experimental studies and computer
      simulations.
AB  - The lack of suited diagnostic tools providing insight into patient specific flow
      characteristics of the nasal airflow is one of the main problems in functional
      diagnosis. Diagnostic methods currently used do not provide the necessary
      information for flow analysis. But the flow distribution is essential for a
      physiological respiration, in particular for cleaning, moistening and tempering
      of the inhaled air as well as for the olfactory function of the nose. To overcome
      this current situation a cooperation project of the ENT surgeons and computer
      graphic engineers was established to develop the computer assisted planning
      system STAN (Simulation Tool for Airflow in the human Nose) combining Computer
      Fluid Dynamics (CFD) with advanced Computer Graphic Technology. The idea of the
      STAN system is to perform patient specific airflow simulations in the patient's
      nasal cavities. Therefore a geometrical model of the nasal airways is derived
      from the patient's tomography scans. A discretization of the surrounded flow
      volume is made by a computational grid. To establish the flow simulation Finite
      Element Methods are performed on the grid. A tailored visualization is offered to
      the surgeon that overlaps the flow pattern to the patient's tomography data shown
      in the coronal, sagittal and transversal plane. The surgeon can not only analyze
      the patient's current respiratory situation he has also the possibility to
      describe the planned surgical intervention. The goal is to simulate the flow
      distribution that can be expected after the surgical intervention and to offer a
      possibility to validate various surgical strategies. To verify the simulation
      results experimental investigations and measurements are made in nasal models.
      Silicon Models of patient's nose channels are made to analyze flow
      characteristics. The CT or MR scans of the same patients are used as input data
      for the simulation. The experimental outcome is compared to the simulation
      results to validate this diagnostic approach.

PMID- 15458108
TI  - Virtual Reality Therapy: case study of fear of public speaking.
AB  - The major goal of this research case study was to investigate the effectiveness
      of Virtual Reality Therapy (VRT) in the treatment of the fear of public speaking.
      A twenty-eight-year-old Caucasian male was selected from questionnaires
      distributed to a class of undergraduate students enrolled at Kennesaw State
      University. Two assessment measures were used in this study. The first measure
      used was the Attitude Towards Public Speaking (ATPS) Questionnaire. The second
      measure used was the eleven-point Subjective Units of Disturbance (SUD) scale.
      These measurements assessed the anxiety, avoidance, attitudes and disturbance
      associated with the subject's fear of public speaking before and after each VRT
      treatment session. This case study of public speaking fear indicates that VRT may
      be used as an effective treatment method for reducing self-reported anxiety.

PMID- 15458109
TI  - Virtual image grafting: image based generation and visualization of virtual skin
      defects.
AB  - We have developed methods for rapidly generating 3d dermatologic datasets for use
      in education, training simulations and procedure planning. By compositing local
      surface features of cutaneous wounds onto patient images and 3d models, one can
      flexibly generate large patient variability from a small initial 3d library. The
      wound database is generated from clinically captured photographic images. The
      wound image is extracted from the image of the surrounding tissue. The 3d anatomy
      database is generated from MRI scans and from multiple photographic views.
      Extracted wound images can be moved rotated and scaled and blended in the final
      composite.

PMID- 15458110
TI  - In vivo measurement of solid organ visco-elastic properties.
AB  - To support the ongoing development of software-based surgical simulation systems,
      work is underway to acquire the mechanical properties of living tissue. When such
      simulations include force feedback, visco-elastic properties must be evaluated
      over a range of frequencies relevant to human perception and motor control. A
      minimally invasive instrument has been developed which can perform normal
      indentation on solid organs, and apply and measure deformations over a frequency
      range from DC to approximately 100Hz. Measurement performance was validated on a
      series of objects and materials with known properties, and the device was
      subsequently used in in vivo tests on porcine liver. Results of these validation
      tests as well as the data extracted from the in vivo experiments are presented.
      Testing in ongoing, and will be expanded to more completely characterize liver,
      as well as porcine spleen and other solid organ tissues. While these animal
      tissue property tests are valuable in and of themselves, they pave the way for
      the development of instruments and experimental protocols suitable for the
      measurement of human tissue properties.

PMID- 15458111
TI  - On defining metrics for assessing laparoscopic surgical skills in a virtual
      training environment.
AB  - One of the key components of any training environment for surgical education is a
      method that can be used for assessing surgical skills. Traditionally, defining
      such a method has been difficult and based mainly on observations. However,
      through advances in modeling techniques and computer hardware and software, such
      methods can now be developed using combined visual and haptic rendering of a
      training scene. This paper presents some ideas on how metrics may be defined and
      used in the assessment of surgical skills in a virtual laparoscopic training
      environment.

PMID- 15458112
TI  - A virtual fluoroscopy system and its use for image guidance in unicompartmental
      knee surgery.
AB  - The C-arm fluoroscope is an indispensable intraoperative 2D imaging device for
      orthopaedic surgery. However, its frequent use in an operation presents a
      significant radiation hazard to the theatre staff and patient. A recent technique
      known as virtual fluoroscopy (VF) enhances the fluoroscope's capability for image
      guided surgery by tracking optically the position of the C-arm, surgical
      instruments and the patient. Virtuality is achieved by overlay of surgical
      instruments onto one or more previously captured fluoroscopic images. A key
      benefit of VF is that it reduces considerably the radiation hazard. This paper
      reports on a new VF technique for tracking and calibration of the fluoroscopic C
      arm. Also reported is the use of our VF system to provide a new image guided
      technique for the accurate placement of the femoral component of unicompartmental
      knee prosthesis.

PMID- 15458113
TI  - Neuropsychological performance and integrated evaluation for disabled people
      using Virtual Reality: integrated VR profile.
AB  - This chapter describes a Virtual Reality (VR) based innovative model of
      evaluation of the performance and potentiality of young mentally/psychically
      disabled subjects with learning difficulties. Using an immersive PC-based VR
      system, the study investigated the characteristics of 150 disabled subjects in
      the EU funded project "Horizon O.D.A.--Catania-1998--2000". The result is the
      definition of an individual neuropsychological "Integrated Profile", based on VR
      performance, that allows an objective functional benchmark between different
      subjects. This model can be used to investigate the possibility of job
      integration for mentally/psychically disabled subjects.

PMID- 15458114
TI  - Virtual environment system for motor tele-rehabilitation.
AB  - The present cutting-edge communication technology applied to the rehabilitation
      may change the real possibility of providing therapeutic treatments to the
      patients at their home. In order to confirm this assertion a current study on
      motor telerehabilitation was undertaken. Through a virtual reality based system,
      and a complementary video conference apparatus, we supplied five post stroke
      patients with a motor rehabilitation therapy. The rehabilitation technique was
      based on the augmented feedback. Subjects underwent the telerehabilitation
      program for six weeks. Before and after the evaluated therapy, arm motor
      performance and the activities of daily living were evaluated by the means of
      clinical scales and measuring the affected arm velocity (end-effector). This
      pilot study suggested that telerehabilitation could promote the learning of arm
      motor abilities at distance from the health facilities. From an economic point of
      view, it could be proposed also as an opportune strategy for saving resources.

PMID- 15458115
TI  - Shared virtual environments for telerehabilitation.
AB  - Current VR telerehabilitation systems use offline remote monitoring from the
      clinic and patient-therapist videoconferencing. Such "store and forward" and
      video-based systems cannot implement medical services involving patient therapist
      direct interaction. Real-time telerehabilitation applications (including remote
      therapy) can be developed using a shared Virtual Environment (VE) architecture.
      We developed a two-user shared VE for hand telerehabilitation. Each site has a
      telerehabilitation workstation with a videocamera and a Rutgers Master II (RMII)
      force feedback glove. Each user can control a virtual hand and interact hapticly
      with virtual objects. Simulated physical interactions between therapist and
      patient are implemented using hand force feedback. The therapist's graphic
      interface contains several virtual panels, which allow control over the
      rehabilitation process. These controls start a videoconferencing session, collect
      patient data, or apply therapy. Several experimental telerehabilitation scenarios
      were successfully tested on a LAN. A Web-based approach to "real-time" patient
      telemonitoring--the monitoring portal for hand telerehabilitation--was also
      developed. The therapist interface is implemented as a Java3D applet that
      monitors patient hand movement. The monitoring portal gives real-time performance
      on off-the-shelf desktop workstations.

PMID- 15458116
TI  - A new approach for the synthesis of glistening effect in deformable anatomical
      objects displayed with haptic feedback.
AB  - An environment mapping approach for texture mapping of anatomical objects with
      glistening was studied and implemented in surgical simulation. A classifier based
      on the generalized goal of achieving glistening effect, which depends on the
      underlying physics and the mapped data, was used as a visual metric and shown to
      be realistic in the presence of achieving the desired quality in real time in the
      presence of haptic feedback. The proposed approach was compared with the standard
      texture mapping approaches used in existing surgical simulation methods that
      generally suffer from texture stretching and with little or no glistening effect.
      In our work, we have successfully applied environment mapping techniques for
      realistic real-time rendering of anatomical objects. We also show several
      examples of anatomical objects with glistening effects that mimic real anatomical
      objects.

PMID- 15458117
TI  - Qualitative and quantitative analysis of pressure sensor data acquired by the E
      Pelvis simulator during simulated pelvic examinations.

PMID- 15458118
TI  - Visual representations of physical abilities: reverse haptic technology?

PMID- 15458119
TI  - Simulation of bleeding during laparoscopic herniorrhaphy.
AB  - Simulation of intragastric bleeding due to an accidental cut by the surgeon is an
      important component of a virtual laparoscopic herniorrhaphy trainer. We present a
      method for simulating bleeding during laparoscopic hemiorrhaphy here. The various
      approaches used in previous research work are reviewed and our present approach
      is justified. Physically based fluid models used in computer graphics are used to
      simulate bleeding.

PMID- 15458120
TI  - A new haptic interface for VR medical training.
AB  - Successful applications of haptic displays are limited to tool-based interfaces
      that simulate haptic effects on surgical and other medical instruments. However,
      no satisfactory haptic display exist so far, that enable the simulation of high
      fidelity palpation of human tissue or body segments. Existing approaches
      developed for medical training fail due to unrealistic haptic effects, time
      consuming donning and doffing, and inconvenient use (e.g., mechatronic tactile
      and kinesthetic displays) or due to restricted function and adjustability (e.g.,
      passive mannequins). The key idea of the new haptic interface is to attach
      artificial organs or segments (e.g. a plastic leg) to a force actuating
      mechatronic unit (e.g. robot). A set of different materials combined in certain
      layers yield components that look and feel like real objects. When the user
      touches the artificial object the contact forces and position changes are
      measured and fed into a model-based controller. Thus, the actuator moves the
      object so that the user gets the impression that he had induced the movement. The
      new haptic display has been verified with a setup developed for the training of
      functional joint evaluation after knee injuries. Compared to classical
      approaches, this display is convenient to use, provides realistic tactile
      properties and can be partly adjusted to different system properties (e.g.
      pathological joint properties). This kind of new interface can be applied to many
      different medical applications, where the clinician directly touches human limbs
      or tissue, such as in obstetrics, reanimation, organ palpation, etc.

PMID- 15458121
TI  - The VEPSY UPDATED project: technical and clinical rationale.
AB  - The emergence of new shared media, such as the Internet and virtual reality are
      changing the ways in which people relate, communicate, and live. Health care, and
      in particular clinical psychology, is one of the areas that could be most
      dramatically reshaped by these new technologies. To exploit and understand this
      potential is the overall goal of the "Telemedicine and Portable Virtual
      Environment in Clinical Psychology"--VEPSY UPDATED--an European Community funded
      research project (IST-2000-25323, http://www.vepsy.com) whose specific goal is
      the development of different PC based virtual reality modules to be used in
      clinical assessment and treatment. In particular the developed modules have been
      using to address the following pathologies: anxiety disorders; male impotence and
      premature ejaculation; obesity, bulimia and binge-eating disorders. The chapter
      details the general technical and clinical characteristics of the developed
      modules.

PMID- 15458122
TI  - e-health in eating disorders: Virtual Reality and telemedicine in assessment and
      treatment.
AB  - e-health, the integration of telehealth technologies with the Internet and shared
      virtual reality could become a significant enabler of consumer health
      initiatives. In fact, they provide an increasingly accessible communication
      channel for a growing part of the population. In the past decade medical
      applications of virtual reality (VR) and telemedicine have been rapidly
      developing, and the technology has changed from a research curiosity to a
      commercially and clinically important area of medical informatics technology. The
      chapter details the characteristics of the Experiential Cognitive Therapy (ECT),
      an integrated inpatient/outpatient (4 weeks) and telemedicine approach (24 weeks)
      that tries to enhance the classical cognitive-behavioral method used in the
      treatment of eating disorders, through VR sessions and telemedicine support in
      the follow-up stage. Particularly, using VR and telemedicine, ECT is able to
      address body experience disturbances, interpersonal relationships, self efficacy
      and motivation to change, key issues for the development and maintenance of
      eating disorders that are somehow neglected by actual clinical guidelines.

PMID- 15458123
TI  - Training and assessment of laparoscopic skills using a haptic simulator.
AB  - Surgical simulation is a promising technique for training of laparoscopic
      surgery. Computer based simulation provides not only a cost effective alternative
      to traditional training but also a way to assess the surgeons performance. In
      this paper, we present a haptic simulator that allows for training and assessment
      of basic laparoscopic skills. The skills trained are modeled around a
      cholecystectomy procedure and include bi-manual dissection, clips setting,
      catheter insertion and cutting. The system uses accurate anatomic models of the
      organs involved in the procedure. This combined with effective methods for soft
      tissue deformation and haptic feedback, giving the surgeon a precise feeling of
      the interaction between organs and surgical instruments, provides a realistic
      training environment. The system has been designed with procedural training in
      mind and by putting together the individual tasks it will be possible to train on
      performing a complete cholecystectomy procedure.

PMID- 15458124
TI  - The Blue DRAGON--a system for monitoring the kinematics and the dynamics of
      endoscopic tools in minimally invasive surgery for objective laparoscopic skill
      assessment.
AB  - Minimally invasive surgeiy (MIS) involves a multi-dimensional series of tasks
      requiring a synthesis between visual information and the kinematics and dynamics
      of the surgical tools. Analysis of these sources of information is a key step in
      mastering MIS surgery but may also be used to define objective criteria for
      characterizing surgical performance. The BIueDRAGON is a new system for acquiring
      the kinematics and the dynamics of two endoscopic tools along with the visual
      view of the surgical scene. It includes two four-bar mechanisms equipped with
      position and force torque sensors for measuring the positions and the
      orientations (P/O) of two endoscopic tools along with the forces and torques
      applied by the surgeons hands. The methodology of decomposing the surgical task
      is based on a fully connected, finite-states (28 states) Markov model where each
      states corresponded to a fundamental tool/tissue interaction based on the tool
      kinematics and associated with unique F/T signatures. The experimental protocol
      included seven MIS tasks performed on an animal model (pig) by 30 surgeons at
      different levels of their residency training. Preliminary analysis of these data
      showed that major differences between residents at different skill levels were:
      (i) the types of tool/tissue interactions being used, (ii) the transitions
      between tool/tissue interactions being applied by each hand, (iii) time spent
      while perfonning each tool/tissue interaction, (iv) the overall completion time,
      and (v) the variable F/T magnitudes being applied by the subjects through the
      endoscopic tools. Systems like surgical robots or virtual reality simulators that
      inherently measure the kinematics and the dynamics of the surgical tool may
      benefit from inclusion of the proposed methodology for analysis of efficacy and
      objective evaluation of surgical skills during training.

PMID- 15458125
TI  - A tutorial platform suitable for surgical simulator training (SimMentor).
AB  - BACKGROUND: The introduction of simulators in surgical training entails the need
      to develop pedagogic platforms adapted to the potentials and limitations provided
      by the information technology. As a solution to the technical challenges in
      treating all possible interaction events and to obtain a suitable pedagogic
      approach, we have developed a pedagogic platform for surgical training,
      SimMentor. METHODS: In SimMentor the procedure to be practiced is divided into a
      number of natural phases. The trainee will practice on one phase at a time,
      however he can select the sequence of phases arbitrarily. A phase is taught by
      letting the trainee alternate freely between 2 modes: 1: A 3-dimensional animated
      guidance designed for learning the objectives and challenges in a procedure. 2:
      An interactive training session through the instrument manipulator device
      designed for training motoric responses based on visual and tactile responses
      produced by the simulator. The two modes are interfaced with the same virtual
      reality platform, thus SimMentor allows a seamless transition between the modes.
      RESULTS: We have developed a prototype simulator for robotic assisted endoscopic
      CABG (Coronary Artery Bypass Grafting) procedure by first focusing on the
      anastomosis part of the operation. Tissue, suture and instrument models have been
      developed and integrated with a simulated model of a beating heart comprises the
      elements in the simulator engine that is used in construction a training platform
      for learning different methods for performing a coronary anastomosis procedure.
      CONCLUSION: The platform is designed for integrating the following features: 1)
      practical approach to handle interactivity events with flexible-objects 3D
      simulators, 2) methods for quantitative evaluations of performance, 3) didactic
      presentations, 4) effective ways of producing diversity of clinical and
      pathological training scenarios.

PMID- 15458126
TI  - Protocols for clinical tests on Parkinson disease affected persons and comparison
      with healthy people with a quantitative method of a new system Daphne.
AB  - This paper deals with Daphne, a portable equipment for the evaluation of the
      state of health in Parkinson disease. The protocols have been developed,
      according to the design, to the characteristics, to the performances of the
      system. Tests on patients and healthy persons are presented, as application of
      protocols.

PMID- 15458127
TI  - First clinical trials for neuromotor analysis.
AB  - This paper deals with a first test model of DAPHNE system, called DDX, which may
      measure the reaction time, the velocity of a finger, the force exerted on a
      button, the tremor of the person, and also the time delay on pronouncing a word
      which appears in the screen of the display. The system is made by a button and a
      spring, with sensors which detect all the parameters. Tests on healthy and
      unhealthy people have been performed to check the validity of the instrument and
      the possibility to use the results in diagnosis and in therapy.

PMID- 15458128
TI  - Stroke rehabilitation at home using virtual reality, haptics and telemedicine.
AB  - The objective of this pilot study is to identify the level of difficulty in which
      subjects with left hemisphere damage in the acute phase after stroke can start
      practicing in a virtual environment. Second, to test an application of Virtual
      Reality technology to existing occupational treatment methods in stroke
      rehabilitation and develop a platform for home rehabilitation controlled
      telemedically. The findings indicate that the system shows potential as an
      assessment and training device. The feasibility study setup is working well
      likewise the assessment method. Developing and increasing the complexity of the
      tasks must be based on the patient individual neurology, and that the cinematic
      motion patterns of the patient's are the basis for exercise design.

PMID- 15458129
TI  - Feature preserving refinement of surfaces for web-based surgical simulation.
AB  - In plastic surgery, 3D models of the affected part are often used for the purpose
      of visualizations and surgical simulations. The optimal models for web-based
      surgical simulations keep high accuracy in affected parts and keep low accuracy
      in other parts. Consequently, the data size becomes small. In this research, we
      propose a method to generate free-form surfaces based on Lattice Structure from
      polygonal meshes. The polygonal meshes are generated automatically from CT and
      MRI data using Marching Cubes. By changing the resolution of input images, the
      accuracy of output meshes is controlled. Free-form surfaces based on Lattice
      Structure are fitted to polygonal meshes. Lattice Structure is a method to manage
      a free-form surface with a simple base polygonal mesh. The data size is quite
      small because surface shape is converted and saved as a simple polygon. A free
      form surface is quickly generated and high accuracy is maintained. Moreover,
      users can input character lines and they are reflected as boundaries of patches.
      The models generated with this method are partly accurate and compact. These data
      make it possible to simulate surgery on the WWW, because they can be quickly
      transferred

PMID- 15458130
TI  - Risk reduction in craniofacial surgery using computer-based modeling and
      intraoperative immersion.
AB  - We present a two-stage concept for risk reduction in craniofacial surgery,
      consisting of preoperative risk modeling and intraoperative risk reduction.
      Preoperatively it is important to find and to visualize risk sources in order to
      minimize them. Our risk model is composed by superimposition of an isotropic risk
      potential and an anisotropic tissue field constituent. It is being applied to
      preoperative planning and simulation of craniofacial surgeries, for example to
      determine an access path with least overall risk value. In the operation room
      risks arise mainly from the absence of preoperative planning and simulation data
      in the operation field. We use a see-through head-mounted display to optimize
      this situation in order to allow the surgeon to maintain accuracy in the whole
      process of computer aided surgery. Main steps of the intraoperative immersion are
      optical tracking of the surgeon wearing the head-mounted display and of the
      patient, registration of preoperatively calculated planning data with the patient
      and visualization of the data within the glasses.

PMID- 15458131
TI  - Adaptive hybrid interpolation techniques for direct Haptic rendering of
      isosurfaces.
AB  - Direct Haptic rendering of voxels from an anatomical dataset provides patient
      specific haptic feedback vital for diagnosis and surgical planning. Our algorithm
      uses zero sets of scalar trivariate function for polynomial interpolation with
      sixty-four neighborhood points to generate isosurfaces on the fly for haptic
      rendering. This approach gives continuity in surfaces as well as better capture
      of isosurface features of the medical dataset. The detailed algorithm is
      presented along with the description of results from haptically rendering medical
      datasets.

PMID- 15458132
TI  - An augmented reality system for ultrasound guided needle biopsies.
AB  - We have developed an augmented reality visualization system that helps the
      physician perform ultrasound guided needle biopsies. For a needle biopsy, the
      needle has to be inserted into an anatomical target to remove a tissue sample.
      Ultrasound guidance is routinely used e.g. for breast needle biopsies. The real
      time ultrasound images allow the physician to locate the target and to monitor
      the needle position. Our system uses a combination of an optical laser guide and
      a virtual guide in the augmented image to provide intuitive guidance for the
      needle placement. There is no need to track the needle, i.e. there is no need to
      instrument the needle for tracking. In phantom tests, users have performed well
      with the system without prior training. This paper describes special features of
      our system and the workflow for the needle placement procedure.

PMID- 15458133
TI  - Automatic patient registration in computer assisted maxillofacial surgery.
AB  - In this paper, a new approach for patient registration in computer assisted
      maxillofacial surgery is presented. The method uses a unique structure of markers
      embedded in a reference frame for the automatic detection of the coordinate
      system of the medical imaging data during the surgical intervention. With the new
      method, the inaccurate and time consuming process of manually identifying markers
      in the data volume and manually teaching them to a navigation system can be
      replaced. The method and algorithms for the automatic marker detection are
      described in this paper. Experiments with 45 data sets of patients proove the
      robustness, usability and safety of the new method. The method has been
      integrated into the navigation system RoboDent for dental implant surgery.

PMID- 15458134
TI  - Exploratory design and evaluation of a user interface for virtual reality
      exposure therapy.
AB  - Virtual reality exposure therapy is slowly becoming a viable option for
      therapists. For virtual reality systems to be used in the daily practice of
      therapists, their usability needs to be taken into consideration. This paper
      describes the current state-of-the-art in interfaces for these systems, and
      describes several proposals for improving the design of these systems. An
      exploratory evaluation is performed to assess the merits of aspects of the
      proposed user interface.

PMID- 15458135
TI  - Limits of human perception of haptic information in Minimally Invasive Surgery
      tools for use in simulation.
AB  - This research looks at the human ability to perceive haptic information when
      using Minimally Invasive Surgery (MIS) tools. In the simulation of MIS it is
      important to understand what haptic information can be perceived by a user.
      Understanding what can be felt allows the force feedback system of the simulator
      to be optimized.

PMID- 15458136
TI  - The DextroBeam: a stereoscopic presentation system for volumetric medical data.
AB  - This paper describes an interaction system called the DextroBeam designed for
      manipulating objects in 3D space while looking at a 3D stereoscopic display
      located in front of the user. Three-dimensional interaction is two-handed and is
      achieved by means of a stylus with a single button or switch. We have been
      planning several neurosurgical cases with the DextroBeam, including the
      separation of Nepalese Siamese twins in April 2001, and have conducted a course
      on surgery of the Temporal Bone (as part of the 9th ASEAN ORL Head and Neck
      Congress in Singapore, March 2001).

PMID- 15458137
TI  - Interactive visualization of four-dimensional ultrasound data.
AB  - We present a hardware-accelerated method using three-dimensional (3D) textures to
      visualize four-dimensional (4D) images of the heart. Novel data subdivision and
      caching ideas enable interactive performance even though 4D data exceed the size
      of 3D texture memory. The capability to visualize 4D images is critical to
      continued evolution and clinical acceptance of 4D imaging.

PMID- 15458138
TI  - Reshaping medical volumetric data for enhanced visualization.
AB  - Three dimensional volume datasets are now commonly produced in the medical
      sciences. These datasets are generated by observational equipment such as CT,
      MRI, and ultrasound. There is a significant amount of research in techniques to
      render these datasets quickly and more realistically. However, there is little or
      no work on intuitive methods to manipulate volume datasets and volume models. For
      example, one may want to view a colon stretched out or unraveled. While
      techniques exist to transform polygonal models, similar techniques are not
      available for volumetric data. In this work, we describe our methodology to
      "reshape volumes" and remap existing volumetric datasets using volumetric
      skeletons. We demonstrate our results by unraveling a 3D colon dataset and
      discuss the many potential uses of this new visualization methodology.

PMID- 15458139
TI  - Visualization of conserved structures by fusing highly variable datasets.
AB  - INTRODUCTION: Skill, effort, and time are required to identify and visualize
      anatomic structures in three-dimensions from radiological data. Fundamentally,
      automating these processes requires a technique that uses symbolic information
      not in the dynamic range of the voxel data. We were developing such a technique
      based on mutual information for automatic multi-modality image fusion (MIAMI
      Fuse, University of Michigan). This system previously demonstrated facility at
      fusing one voxel dataset with integrated symbolic structure information to a CT
      dataset (different scale and resolution) from the same person. The next step of
      development of our technique was aimed at accommodating the variability of
      anatomy from patient to patient by using warping to fuse our standard dataset to
      arbitrary patient CT datasets. METHODS: A standard symbolic information dataset
      was created from the full color Visible Human Female by segmenting the liver
      parenchyma, portal veins, and hepatic veins and overwriting each set of voxels
      with a fixed color. Two arbitrarily selected patient CT scans of the abdomen were
      used for reference datasets. We used the warping functions in MIAMI Fuse to align
      the standard structure data to each patient scan. The key to successful fusion
      was the focused use of multiple warping control points that place themselves
      around the structure of interest automatically. The user assigns only a few
      initial control points to align the scans. Fusion 1 and 2 transformed the atlas
      with 27 points around the liver to CT1 and CT2 respectively. Fusion 3 transformed
      the atlas with 45 control points around the liver to CT1 and Fusion 4 transformed
      the atlas with 5 control points around the portal vein. The CT dataset is
      augmented with the transformed standard structure dataset, such that the warped
      structure masks are visualized in combination with the original patient dataset.
      This combined volume visualization is then rendered interactively in stereo on
      the ImmersaDesk in an immersive Virtual Reality (VR) environment. RESULTS: The
      accuracy of the fusions was determined qualitatively by comparing the transformed
      atlas overlaid on the appropriate CT. It was examined for where the transformed
      structure atlas was incorrectly overlaid (false positive) and where it was
      incorrectly not overlaid (false negative). According to this method, fusions 1
      and 2 were correct roughly 50-75% of the time, while fusions 3 and 4 were correct
      roughly 75-100%. The CT dataset augmented with transformed dataset was viewed
      arbitrarily in user-centered perspective stereo taking advantage of features such
      as scaling, windowing and volumetric region of interest selection. CONCLUSIONS:
      This process of auto-coloring conserved structures in variable datasets is a step
      toward the goal of a broader, standardized automatic structure visualization
      method for radiological data. If successful it would permit identification,
      visualization or deletion of structures in radiological data by semi
      automatically applying canonical structure information to the radiological data
      (not just processing and visualization of the data's intrinsic dynamic range).
      More sophisticated selection of control points and patterns of warping may allow
      for more accurate transforms, and thus advances in visualization, simulation,
      education, diagnostics, and treatment planning.

PMID- 15458140
TI  - A system for simulation and monitoring of robot-assisted and navigation-assisted
      surgical interventions. (Part 1).
AB  - Location monitoring systems for surgical applications are getting more and more
      common in clinical daily life. Navigation treatment systems are also a form of a
      location monitoring system. These systems always consist of an optical, US-,
      electromagnetic or mechanical navigation system. If two or more navigation
      systems are combined or one navigations system is combined with a robot system
      the kinematic model of the entire system consists of closed kinematic loops. In
      this paper, an approach is presented to gain more information from the closed
      kinematic chains instead of breaking the kinematic loops.

PMID- 15458141
TI  - A new approach for modelling kinematic dependencies for monitoring locations of
      objects in closed kinematic chains. (Part 2).
AB  - Location monitoring systems for surgical applications are getting more and more
      common in clinical daily life. Navigation treatment systems are also a form of a
      location monitoring system. These systems always consist of an optical, US-,
      electromagnetic or mechanical navigation system. If two or more navigation
      systems are combined or one navigations system is combined with a robot system
      the kinematic model of the entire system consists of closed kinematic loops. In
      this paper, an approach is presented to gain more information from the closed
      kinematic chains instead of breaking the kinematic loops. This is the second part
      of [1].

PMID- 15458142
TI  - Temporal bone dissection simulation--an update.
AB  - We report on our continued development of a virtual simulation for temporal bone
      dissection that provides stereoscopic display, haptic feedback, and aural
      simulation into a straightforward, comprehensive learning environment. The
      multimodal interface provides a seamless simulation for non-deterministic
      drilling and cutting of bone in the surgical context, as well as an intuitive
      interface for the intelligent tutor for learning regional anatomy. We present
      novel methodologies for integrating multimodal and multiresolution data sets,
      including extension to functional and structural segmentation. We will present
      our initial efforts to validate this environment. Through continued iterations,
      it is our hope that the system will provide a valuable tool for training future
      otologic surgeons as well as an environment for the quantitative evaluation of
      surgical skill.

PMID- 15458143
TI  - Measurement of in-vivo force response of intra-abdominal soft tissues for
      surgical simulation.
AB  - The lack of data on in-vivo material properties of soft tissues has been a
      significant impediment in the development of virtual reality based surgical
      simulators that can provide the user with realistic visual and haptic feedback.
      As a first step towards characterizing the mechanical behavior of organs, this
      work presents in-vivo force response of the liver and lower esophagus of pigs
      when subjected to ramp and hold, and sinusoidal indentations delivered using a
      haptic feedback device, Phantom, employed as a mechanical stimulator. The results
      show that pulse significantly affects the reaction forces and that the lower
      esophagus is 2 to 2.5 times stiffer than the liver.

PMID- 15458144
TI  - Estimation of soft-tissue model parameters using registered pre- and
      postoperative facial surface scans.
AB  - Computer-based techniques for the simulation of craniofacial surgical procedures
      and for the prediction of the surgical outcome have been shown to be very useful.
      However, the assessment of the accuracy of the simulated surgical outcome is
      difficult. In this paper, a technique is described which allows to compare the
      simulated surgical outcome and the actual surgical result. The simulated
      postoperative patient's appearance is compared to a second surface scan which is
      obtained postoperatively. The pre- and postoperative surface scans, which are
      different due to the surgery, are registered employing a robust registration
      method which minimizes distances of corresponding points. Parameters of the soft
      tissue model can be adapted with respect to minimized differences of
      corresponding points of the simulated postoperative and the actual postoperative
      surface of a patient's face.

PMID- 15458145
TI  - Virtual endoscopy using spherical QuickTime-VR panorama views.
AB  - Virtual endoscopy needs some precomputation of the data (segmentation, path
      finding) before the diagnostic process can take place. We propose a method that
      precomputes multinode spherical panorama movies using Quick-Time VR. This
      technique allows almost the same navigation and visualization capabilities as a
      real endoscopic procedure, a significant reduction of interaction input is
      achieved and the movie represents a document of the procedure.

PMID- 15458146
TI  - Integration of intraoperative radiotherapy (IORT) dose distribution into the
      postoperative CT-based external beam radiotherapy (EBRT) treatment planing.
AB  - In the treatment of malignant disease external beam radiation therapy (EBRT) is
      often combined with surgery. Intraoperative radiotherapy (IORT) improves the
      local control by dose escalation. For reasons of recording, improvement and
      security of the intervention, it would be necessary to merge the IORT-dose
      distribution with the postoperative CT-based EBRT-planing. The aim of this work
      was to develop a method to reconstruct the IORT field and register it with the
      postoperative planing CT. This enables the reconstruction of the IORT dose
      distribution and merge it with the CT-based EBRT planing data. We use a surface
      scanner to receive a large amount of surface points which enables us reconstruct
      the IORT-field and to register it with the CT-based EBRT planning data. Scanning
      and calculation time is not over 2 seconds, depending mainly on the CPU power.
      The error of a single point is below 1 mm. The density of the point cloud is
      approx. 4 per mm2. In this paper we give an overview of our experimental setup
      and the accuracy of the method.

PMID- 15458147
TI  - The application of eyeglass displays in changing the perception of pain.
AB  - We have been examining the potential value of visual stimulation via the eyeglass
      displays in changing the perception of pain. In this randomized, controlled,
      cross-over study, 72 healthy university student volunteers were asked to wear a
      light-weighted eyeglass projecting a feeling of watching a fifty-two-inch
      television screen in a close distance while pain was produced by a modified
      tourniquet technique. There is a significant increase of pain threshold and pain
      tolerance with the effect of visual stimulation. These findings having
      implications of using visual stimulation as positive adjunct to other methods of
      pain relief and to different pain conditions in clinical areas.

PMID- 15458148
TI  - Evaluation of visualization techniques for image-guided navigation in liver
      surgery.
AB  - A substantial component of an image-guided surgery system (IGSS) is the kind of
      three-dimensional (3D) presentation to the surgeon because the visual depth
      perception of the complex anatomy is of significant relevance for orientation.
      Therefore, we examined in this contribution four different visualization
      techniques, which were evaluated by eight surgeons. The IGSS developed by our
      group supports the intraoperative orientation of the surgeon by depicting a
      visualization of the spatially tracked surgical instruments with respect to
      intrahepatic vessels that have to be conserved vitally, the tumor, and
      preoperatively calculated resection planes. In the prelimenary trial presented
      here we examined the human ability to percept an intraoperative virtual scene and
      to solve given navigation tasks. The focus of the experiments was to measure the
      ability of eight surgeons to orientate intrahepaticaly and to transfer the
      percepted spatial relation to movements in real space. An autostereoscopic
      visualization with a prism-based display yielded that the navigation can be
      performed faster and more accurately than with the other visualization
      techniques.

PMID- 15458149
TI  - Enhanced stereographic x-ray images.
AB  - This project extends previous work on stereographic projection of 2D x-ray images
      and aims to overcome a number of problems, namely: confusing stereo cues;
      distortion between stereo pairs; and increased radiation exposure from additional
      x-ray images. Images are distortion corrected and a polygonal representation of a
      bone fitted to the x-ray image, to approximate the bone surface. The polygonal
      representation is rendered and blended with the x-ray image to add surface
      detail, without obscuring salient features within the original x-ray. A reduction
      in x-ray exposure by using a stereo pair of computer-generated polygonal bone
      images blended with a mono x-ray image is investigated. An experiment provides
      evidence that depth perception is increased with the inclusion of bone surface
      rendering, and is achievable with a mono x-ray image.

PMID- 15458150
TI  - The communication between therapist and patient in virtual reality: the role of
      mediation played by computer technology.
AB  - Even if the number of reported application is constantly increasing,
      understanding how to use immersive virtual reality (VR) to support clinical
      practice presents a substantial challenge for the designers and users of this
      emerging technology. These opposite faces are resulting from the peculiar
      characteristics of VR. In fact, VR is not simply a particular collection of
      technological hardware, but can be considered as a new medium defined in terms of
      its effect on both basic and major psychological processes. In particular, the
      essence of VR is the inclusive relationship between the participant and the
      virtual environment, where direct experience of the immersive environment
      constitutes communication. Starting from this vision, the chapter tries to
      outline a theoretical framework for supporting the development and tuning of
      clinical oriented VR systems.

PMID- 15458151
TI  - Virtual reality assisted cognitive behavioral therapy for the treatment of Panic
      Disorders with Agoraphobia.
AB  - The chapter describes the characteristics of the Experiential-Cognitive Therapy
      (ECT) protocol for Panic Disorder and Agoraphobia. The goal of ECT is to
      decondition fear reactions, to modify misinterpretational cognition related to
      panic symptoms and to reduce anxiety symptoms. This is possible in an average of
      eight sessions of treatment plus an assessment phase and booster sessions,
      through the integration of Virtual Experience and traditional cognitive
      behavioral techniques. We decided to employ the techniques included in the
      cognitive-behavioral approach because they showed high levels of efficacy.
      Through virtual environments we can gradually expose the patient to feared
      situation: virtual reality consent to re-create in our clinical office a real
      experiential world. The patient faces the feared stimuli in a context that is
      nearer to reality than imagination. For ECT we developed the Virtual Environments
      for Panic Disorders--VEPD--virtual reality system. VEPD is a 4-zone virtual
      environment developed using the Superscape VRT 5.6 toolkit. The four zones
      reproduce different potentially fearful situations--an elevator, a supermarket, a
      subway ride, and large square. In each zone the characteristics of the anxiety
      related experience are defined by the therapist through a setup menu.

PMID- 15458152
TI  - Dextrous and shared interaction with medical data: stereoscopic vision is more
      important than hand-image collocation.
AB  - The current experiment was carried out to extend our knowledge about the relative
      importance of stereoscopic display and hand-image collocation for dextrous
      interaction. We devised a new task, the Volumetric Dexterity Test (VDT), which
      quite accurately duplicates the way professional personnel such as surgeons and
      radiologists interact with detailed medical data in a VR environment. Our results
      were surprising. Stereo vision was very important to both accuracy and speed of
      task completion, as we found previously. But the presence of hand-image
      collocation did not improve accuracy, despite the fact that this was a truly
      three-dimensional task. If this finding is borne out it has important
      implications for the volumetric presentation of medical data to individual
      practitioners and in group settings.

PMID- 15458153
TI  - Usability analysis of VR simulation software.

PMID- 15458154
TI  - Elastically deformable 3D organs for haptic surgical simulation.
AB  - This paper describes a technique for incorporating real-time elastically
      deformable 3D organs in haptic surgical simulators. Our system is a physically
      based particle model utilizing a mass-springs-damper connectivity with an
      implicit predictor to speed up calculations during each time step. The solution
      involves repeated application of Newton's 2ndd Law of motion: F = ma using an
      implicit solver for numerically solving the differential equations.

PMID- 15458155
TI  - A generic arthroscopy simulator architecture.
AB  - Virtual Environments offer considerable potential to improve training for
      arthroscopic surgery. However, current systems are developed for individual
      joints, which requires healthcare providers to purchase and maintain multiple
      environments with differing interfaces and capabilities. This paper describes a
      generic arthroscopy system architecture that allows the fast development of
      training environments for any joint, each sharing a common user-interface. The
      use of the architecture in developing a simple ankle simulator is also described.

PMID- 15458156
TI  - Virtual reality in 3D echocardiography: dynamic visualization of atrioventricular
      annuli surface models and volume rendered Doppler-ultrasound.
AB  - Knowledge about annuli shape and blood flow patterns, both optimally assessed by
      transesophageal 3D Doppler echocardiography, can be used in computer assisted
      surgical planning of heart valve reconstruction. Moreover, information about the
      individual shape of the annulus anatomy can guide the design of annular
      prostheses. The problem is that the annulus cannot be easily differentiated from
      the valve and the myocardium with standard visualization methods. We have
      developed a nearly automatic method for annulus segmentation. The algorithm
      provides the annulus shape in a symbolic description, which can be used for
      surface visualization. Best results to visualize the blood flow from the Doppler
      signal and the myocardial morphology are obtained by volume rendering. A hybrid
      visualization technique combining surface rendering and volume rendering enables
      to dynamically visualize the surface rendered annulus combined with a volume
      rendered 3D (plus time) reconstruction of either backscatter (morphology) and
      Doppler information (in original color coding), or together with backscatter only
      or Doppler only. Visualization of annuli structures combined with blood flow and
      general myocardial morphology provides a new tool to analyze heart diseases.

PMID- 15458157
TI  - Engineering and algorithm design for an image processing Api: a technical report
      on ITK--the Insight Toolkit.
AB  - We present the detailed planning and execution of the Insight Toolkit (ITK), an
      application programmers interface (API) for the segmentation and registration of
      medical image data. This public resource has been developed through the NLM
      Visible Human Project, and is in beta test as an open-source software offering
      under cost-free licensing. The toolkit concentrates on 3D medical data
      segmentation and registration algorithms, multimodal and multiresolution
      capabilities, and portable platform independent support for Windows, Linux/Unix
      systems. This toolkit was built using current practices in software engineering.
      Specifically, we embraced the concept of generic programming during the
      development of these tools, working extensively with C++ templates and the
      freedom and flexibility they allow. Software development tools for distributed
      consortium-based code development have been created and are also publicly
      available. We discuss our assumptions, design decisions, and some lessons
      learned.

PMID- 15458158
TI  - Finite element (FE) modeling of the mandible: from geometric model to tetrahedral
      volumetric mesh.
AB  - This paper presents our experience in using FE modeling of clinically relevant
      cases specifically in mandibular surgery. A semi-automatic procedure integrated
      with a group of Virtual Basic-based codes has been developed to clean the
      geometric models. Consequently, the time required for generate the tetrahedral
      volumetric mesh of mandible from patient-specific CT data has been reduced to
      less than 40 hours. Pre- and post-operation FE meshes are shown to be consistent
      and can be used for further modeling and analysis.

PMID- 15458159
TI  - Law and standards faced with market rules.

PMID- 15458160
TI  - Why we need standardisation in Healthcare security.
AB  - This chapter presents the benefits resulting from standardisation in the field of
      Security in Healthcare Information Systems (HIS). Especially in the EU,
      standardisation appears as a key element for the effectiveness of the Single
      Market and the competitiveness of European industry.

PMID- 15458161
TI  - Overview on security standards for Healthcare information systems.
AB  - The intense need for Healthcare information exchange has revealed a lack of
      interoperability of systems and applications. Security controls, usually based on
      proprietary methods and techniques, aggravate the current situation. However,
      timely development of HIS security standards may improve the interoperability and
      enable the integration of systems. This chapter provides an overview of the
      standardisation work that is being done by official standardisation organisations
      in Europe and world-wide.

PMID- 15458162
TI  - Draft standard for high level security policies for Healthcare establishments.

PMID- 15458163
TI  - Draft secure medical database standard.
AB  - Medical database security is a particularly important issue for all Healthcare
      establishments. Medical information systems are intended to support a wide range
      of pertinent health issues today, for example: assure the quality of care,
      support effective management of the health services institutions, monitor and
      contain the cost of care, implement technology into care without violating social
      values, ensure the equity and availability of care, preserve humanity despite the
      proliferation of technology etc.. In this context, medical database security aims
      primarily to support: high availability, accuracy and consistency of the stored
      data, the medical professional secrecy and confidentiality, and the protection of
      the privacy of the patient. These properties, though of technical nature,
      basically require that the system is actually helpful for medical care and not
      harmful to patients. These later properties require in turn not only that
      fundamental ethical principles are not violated by employing database systems,
      but instead, are effectively enforced by technical means. This document reviews
      the existing and emerging work on the security of medical database systems. It
      presents in detail the related problems and requirements related to medical
      database security. It addresses the problems of medical database security
      policies, secure design methodologies and implementation techniques. It also
      describes the current legal framework and regulatory requirements for medical
      database security. The issue of medical database security guidelines is also
      examined in detailed. The current national and international efforts in the area
      are studied. It also gives an overview of the research work in the area. The
      document also presents in detail the most complete to our knowledge set of
      security guidelines for the development and operation of medical database
      systems.

PMID- 15458164
TI  - Demonstration results for the standard ENV 12924.
AB  - Within the working programme of CEN/TC251 (Health Informatics), a standard for
      Security Categorisation and Protection for Healthcare Information Systems has
      been developed. This document was formally adopted in 1997 by CEN as pre-standard
      CEN ENV 12924. A demonstration and implementation effort, which was to be
      effected in principle at one location, was planned and executed as part of the
      MEDSEC project. The standard CEN ENV 12924 contains a security categorisation
      model for information systems in Healthcare, distinguishing six categories, plus
      some refinements. For each category it specifies the required protection
      measures. The project task consisted of demonstrating and implementing the
      standard (as far as possible within a limited period) in a real life situation,
      and providing feedback on these results to the CEN organisation. To this end, the
      categorisation scheme, as specified in the standard, was applied to a large part
      of the information (sub)-systems in the Leiden University Medical Centre. A set
      of ten sub-systems was then selected for a more detailed investigation. The
      actual protection status for each sub-system was evaluated on the basis of the
      recommended protection profiles specified in the standard. For each of the
      relevant recommendations in the standard, its status was recorded, and remarks
      were added on its relevance, feasibility, etc. These detailed data have been
      gathered in separate reports for each sub-system. These reports evidently are
      confidential, in view of protection of the hospital's information security. A
      similar, though more limited exercise has been done at Magdeburg University
      Hospital (UHM), in order to be able to allow for possible differences in local
      situations. A thorough comparison of results for different hospitals was beyond
      the scope of the project, however. From the overall picture we have tried to draw
      conclusions on the quality, completeness and applicability of the standard, as
      well as on the actual level of protection of the systems. As a by-product of the
      investigation, for all systems out of the small group, implementation plans have
      been specified to bring the protection in the various (sub)-systems on a higher
      level, where necessary. Subsequently, these plans have been realised to a large
      extent. To facilitate the bookkeeping of the results, we have used the SIDERO
      model, resulting from the SEISMED project. This model has been enhanced, for this
      purpose, with the recommendations from this standard. A brief description of this
      database model has been included in Appendix B. As an overall conclusion, we may
      state that the standard has proven to be a very useful instrument, providing a
      good basis for a security review of the types of Healthcare information systems
      which are encountered in a hospital environment. Some suggestions have been
      presented, for amending recommendations that were found too unpractical or too
      heavy in the circumstances considered. Also, we suggest to add one category to
      the set of six which is being used now. Furthermore, the use of a 'bookkeeping
      tool' (like e.g. SIDERO) is strongly recommended.

PMID- 15458165
TI  - Secure HL7 transactions using Internet mail (Internet draft).
AB  - The document describes the applicability of the Internet standardisation efforts
      on secure electronic data interchange (EDI) transactions for Health Level-7
      (HL7), an EDI standard for Healthcare used world-wide. The document heavily
      relies on the work in progress by the IETF EDIINT working group. It is in most
      parts a restatement of the EDIINTs requirements document and application
      statement 1 (AS#1) tailored to the needs of the HL7 audience. The authors tried
      to make the document as self consistent as possible. The goal is to give to the
      reader who is not a security or Internet standards expert enough foundational and
      detail information to enable him to build communication software that complies to
      the Internet standards. Even though the authors rely on and promote the
      respective Internet standards and drafts, they did not withstand from commenting
      on and criticising the work where they see upcoming problems in use with HL7 or
      other EDI protocols that have not been in the initial focus of the EDIINT working
      group. The authors make suggestions to add parameters to the specification of the
      MIME type for EDI messages in RFC 1767 in order to enhance functionality. The
      authors give use cases for a larger subset of disposition types and modifiers of
      message disposition notifications. One key issue where the document goes beyond
      the current EDIINT drafts is the concept of non-repudiation of commitment to an
      EDI transaction. Secure EDI transactions should be regarded as "distributed
      contracts," i.e. not only the sending and receiving of single messages should be
      non-refutable but also the connection between messages interchanges. In
      anticipation of this requirement HL7 usually requires a response message to be
      sent to acknowledge every transaction. The authors therefore have the requirement
      to securely couple an EDI response message to its request message. Given the
      current shape of RFC 1767 this is generally possible only if a response message
      is coupled with an MDN receipt and the combination of both signed by the
      responder. The document describes a protocol to bundle MDN and response that uses
      the MIME multi-part/related content type in RFC 2112.

PMID- 15458166
TI  - Standard guide for EDI (HL7) communication security.

PMID- 15458167
TI  - Standard guide for implementing HL7 communication security.

PMID- 15458168
TI  - IT security training in the Healthcare environment.

PMID- 15458169
TI  - A dose of higher costs. With drug manufacturers being hit with new fees from
      distributors, providers and GPOs face new pricing pressures.
AB  - There's change afoot among drug distributors, who are hitting manufacturers with
      new fees. Those pricing pressures are expected to be felt elsewhere in the
      industry. "I think the impact will eventually ... be felt in some way by
      providers in increased cost or lack of product," says Larry Dooley, left, of
      Novation.

PMID- 15458170
TI  - Staying the healthcare course. Bush speech reveals no dramatic health policy
      shift.

PMID- 15458171
TI  - Estimating the cost of quality: QIOs' expanded role is welcome but needs funding.

PMID- 15458172
TI  - Testing the limits: four systems vie to build first hospital in Minn. suburb.

PMID- 15458173
TI  - Living with an allowance: Maine hospitals review new capital-spending limits.

PMID- 15458174
TI  - Nursing a shortage: vacancies dip, but lack of instructors adds to woes.

PMID- 15458175
TI  - Campaign for sale: Tenn. system peddles ad ideas for trimming ER visits.

PMID- 15458176
TI  - It's Greenspan who should recalibrate: support for big tax cuts belies concern
      over future of medicare, social security.

PMID- 15458177
TI  - An IT Trojan horse...or a necessary partner. Feds should stay out of 'evidence
      based' medicine.

PMID- 15458178
TI  - An IT Trojan horse...or a necessary partner. Government, industry must work
      together on IT.

PMID- 15458179
TI  - Gone shopping: more employers show interest in health savings accounts, helping
      to accelerate the consumer-driven healthcare movement.

PMID- 15458180
TI  - Full-court press: plaintiff lawyer Scruggs scored big in his litigation against
      big tobacco; now he's taking on hospitals.

PMID- 15458181
TI  - Magnetic resonance imaging of rectal cancer: what radiation oncologists need to
      know.

PMID- 15458182
TI  - Neoadjuvant radiochemotherapy in rectal cancer: for which patients and tumor
      stages?

PMID- 15458183
TI  - Overview of the role of preoperative radiotherapy to increase sphincter
      preservation for rectal cancer.

PMID- 15458184
TI  - Surgery alone: is total mesorectal excision sufficient for rectal cancer?

PMID- 15458185
TI  - Recurrent rectal cancer: how to predict resectability?

PMID- 15458186
TI  - A multicenter analysis of 123 patients with recurrent rectal cancer within the
      pelvis.

PMID- 15458187
TI  - Intraoperative radiotherapy--special focus: recurrent rectal carcinoma.

PMID- 15458188
TI  - Local recurrence of rectal carcinoma: radio-oncologic strategies.

PMID- 15458189
TI  - Diagnostic imaging of pancreatic cancer--the role of PET.

PMID- 15458190
TI  - Adjuvant radiochemotherapy in pancreatic cancer: contra.

PMID- 15458191
TI  - Adjuvant radiochemotherapy for pancreatic cancer--why we might need it even more.

PMID- 15458192
TI  - Radiochemotherapy in unresectable pancreatic cancer.

PMID- 15458193
TI  - Surgical resection of colorectal metastases.

PMID- 15458194
TI  - Stereotactic radiation therapy of liver metastases: update of the initial phase
      I/II trial.

PMID- 15458195
TI  - Laser-induced thermotherapy of liver metastases.

PMID- 15458196
TI  - [Adaptive value of genes controlling the level of biogenic amines in Drosophila].
AB  - The effects of mutations that change the level of biogenic amines (octopamine and
      dopamine) on stress-reactivity and fitness of Drosophila imagoes are considered.
      It has been shown that (1) the biogenic amines represent an important but not
      triggering factor of the development of stress reaction; (2) under normal
      conditions, reproduction is regulated by genes that control dopamine metabolic
      pathways (indirectly via regulation of the juvenile hormone level). Under
      unfavorable conditions, reproduction is regulated by genes that control
      octopamine metabolism; (3) heat-stress adaptation depends on expression of genes
      controlling the background level of dopamine.

PMID- 15458197
TI  - [Analysis of genetic variation in rare endemic species Oxytropis chankaensis
      Jurtz. (Fabaceae) using RAPD markers].
AB  - The method of polymerase chain reaction with random primers (RAPD) was used to
      assess genetic variation and population differentiation in the rare endemic plant
      Oxytropis chankaensis Jurtz. (Fabaceae). DNA samples from plants of two isolated
      populations were compared at 133 loci detected by use of ten primers. Both
      populations examined were characterized by high polymorphism levels (P95 = 72.9%,
      A = 1.92 and P95 = 74.4%, A = 1.88, respectively). They were also statistically
      significantly different in the frequencies of most of the amplicons. For each of
      the plants, unique multilocus RAPD phenotype was established using 17 to 20 RAPD
      markers. Diagnostic markers were not revealed. The populations were poorly
      differentiated. On average, the between-population component accounted for about
      8% of the variation, while 92% of the variation was detected within populations.
      High variation along with the low degree of differentiation characteristic of two
      most geographically remote populations of O. chankaensis can have several
      explanations, among which a polyploid origin of the species seems to be most
      important.

PMID- 15458198
TI  - [Frameshift suppression through inactivation of translation termination in yeast
      Saccharomyces cerevisiae: significance of the local context].
AB  - Site-directed mutagenesis and nucleotide sequence analysis were used to study the
      roles of the global and local contexts in suppression of the lys2-90 frameshift
      (FS) mutation in Saccharomyces cerevisiae. Global context features established
      for the LYS2 mRNA region containing the extra T (lys2-90) were similar to those
      characteristic of regions involved in translational frameshifting. These were a
      potential ability of the region to form a pseudoknot and the presence of
      heptanucleotide CUU UGA C with the "hungry" UGA nonsense codon in the pseudoknot.
      Some local context features proved to be essential for the phenotypic expression
      of FS suppression as a result of translational frameshifting. Two amino acid
      substitutions determined by the nucleotide sequence between the extra U and the
      UGA nonsense codon lacked expression. A dependence was observed between the
      efficiency of FS suppression and the type of the nonsense codon located at a
      particular position downstream of the extra nucleotide (UGA > UAG > UAA). When
      translation termination was inactivated, nonsense suppression and FS suppression
      correlated with each other. These results suggest that translational
      frameshifting, which underlies suppression in the case of inactivation of
      translation termination, most likely takes place on the nonsense codon arising as
      a result of insertion of an extra nucleotide.

PMID- 15458199
TI  - [The main effect of chromosomal rearrangement is changing the action of
      regulatory genes].
AB  - Effect of chromosomal rearrangements on the expression of mutations was studied
      in Drosophila melanogaster regulatory genes. These were facultative dominant
      lethals and recessive lethals on the X chromosome obtained by the classical
      Muller-5 method. Chromosomal rearrangements drastically changed the expression of
      regulatory gene mutations. Rearrangements either caused the lethal effect of
      mutations or suppressed the already present lethality. The action of
      rearrangements exhibited the maternal or paternal effect. Irrespective of the
      presence in the genome of mutations at regulatory genes, a rearrangement acted as
      a factor decreasing fertility of the organism. The rearrangement effect is
      identical to the expression of regulatory genes per se. It is concluded that the
      chromosomal rearrangement affects the examined regulatory genes indirectly
      through a change in the operation of regulatory genes located within the
      rearrangement. Thus, rearrangements gain great importance for the definition of
      the pattern of genome functional activity. Widespread distribution of
      rearrangements in individual genotypes and their effectivity in the process of
      speciation are thus explained.

PMID- 15458200
TI  - [Study of male mating behavior in some Drosophila melanogaster strains in
      experiments with fertilized females].
AB  - Male courtship ritual is among the main behavioral characteristics of Drosophila.
      This is a complex, genetically determined process consisting of four general
      stages: orientation, vibration, licking, and attempts at copulation (or
      successful copulation). Several genes are known that control some stages of this
      behavior. Most of them have pleiotropic effects and are involved in other
      biological processes. Earlier, we have shown that a mutation in locus flamenco
      (20A1-3), which controls transposition and infectivity of retrotransposon gypsy
      (MDG4), is involved in the genetic control of behavior. In strains mutant for
      this locus, the male mating activity is decreased and the structure of courtship
      ritual is changed. To understand the mechanisms of these changes, it is important
      to study all behavioral stages in genetically identical strains. For this
      purpose, the normal allele of gene flamenco from the X chromosome of the wild
      type strain (stock) Canton S was introduced into strain SS carrying flamMS. This
      offers new opportunities in studying the role of gene flamenco in the control of
      mating behavior in Drosophila.

PMID- 15458201
TI  - [Identification and mapping of chi115 gene and DNA markers linked to it in pea
      (Pisum sativum L.)].
AB  - Chlorophyll mutant Chi115 was induced by ethylmethane sulfonate (EMS) treatment
      of seeds of genotype Torsdag in Moscow State University and is characterized by
      lighter plant color. The monogenic nature of the mutant was determined by
      analyzing the F2 population from a cross between two P. sativum genotypes, WL1238
      and Chi115. To establish a local map around the chi115 gene, the RAPD and ISSR
      techniques were used with 45 RAPD and 10 ISSR primers in combination with bulked
      segregant analysis (BSA). Linkage of 12 RAPDs and 2 ISSRs to the chi115 locus was
      observed in analysis of F2 single plants. Two RAPD markers that were closely
      associated with the chi115 gene were converted into the sequence characterized
      amplified region (SCAR) markers. By lowering the LOD score to 2, the linkage
      group containing the chi115 gene could be linked to the b gene (color of the
      flower) on linkage group III. Nevertheless, to prove the result obtained, three
      CAPS markers Sodmt, TubA1, and Rb were chosen on linkage group III. The results
      of linkage analysis showed that these CAPS markers were located within the
      linkage group including the chi115 gene.

PMID- 15458202
TI  - [Variation and morphogenetic characteristics of different Stachys species during
      microclonal propagation].
AB  - Morphogeneses of Stachys different species introduced in culturing in vitro have
      been compared. The frequency of altered forms have been demonstrated to be
      related to the plant genotype. All regenerants of S. sieboldii, which reproduces
      in vivo only vegetatively, are phenotypically normal, irrespective of the
      concentrations of plant growth regulators at which they have been obtained. Only
      changes in isozyme patterns have been observed in the regenerants grown in media
      containing at least 10 mg/l benzyl aminopurine (BAP); most of these changes are
      the absence of a particular component of the pattern. The cross-pollinating
      species Stachys ocymastrum, which typically reproduces by seeds, has yielded
      morphologically altered forms even in phytohormone-free media; its isozyme
      patterns often contained a new component. Analysis of the isoperoxidase patterns
      of regenerants of both Stachys species obtained with the use of high phytohormone
      concentrations has demonstrated qualitative and quantitative changes suggesting
      the appearance of somaclonal variants even in the course of plant regeneration
      directly from nodal segments, bypassing callus formation. Changes have also been
      found in Stachys plants regenerating from the callus tissue.

PMID- 15458203
TI  - [The effect of heterozygosity for marker loci on recombination fraction in
      adjacent chromosomal regions in maize].
AB  - Analysis of maize F2 plants revealed a decrease in the recombination fraction
      (rf) between the marker loci in case of heterozygosity of adjacent chromosomal
      regions. The relative decrease in rf was positively associated with the length of
      the heterozygous region. Heterozygosity had no effect on rf in other chromosomes.
      These results can be explained by defective pairing of heterozygous chromosomal
      regions in meiosis.

PMID- 15458204
TI  - [Epiplastome variation of the number of chloroplasts in stomata guard cells of
      sugar beet (Beta vulgaris L.)].
AB  - In stomata guard cells of sugar beet, variation in the number of chloroplasts was
      studied in successive generations: (1) hybrid generation; (2) generation yielded
      by uniparental apozygotic seed reproduction; (3) generation obtained after seed
      treatment with a colchicine solution; (4) generation obtained after seed
      treatment with 5-azacytidine. As compared to hybrid generation, uniparental seed
      reproduction increases the average number of chloroplasts in stomata guard cells
      (from 13.5 to 15.0) and decreases distribution variance of this trait by a factor
      of 3 to 4. Colchicine increases both average number of chloroplasts in stomata
      guard cells (from 13.5 to 18.2) and distribution variance (about twice). 5
      Azacytindine reduces the number of chloroplasts in cells (from 15.0 to 12.9) but
      enhances distribution variance (about 1.5 times). Variation in the number of
      chromosomes in stomata cells is related to myxoploidy in meristem tissue, on the
      one hand, and to the rate of cell division, on the other. Uniparental seed
      reproduction is suggested to enhance the number of organelles per cell due to
      high myxoploidy in cell populations, which is typical of inbred plants.
      Colchicine blocks spindle division and sharply increases the level of myxoploidy
      in cell populations and the number of organelles per cell. 5-Azacytidine
      hypomethylates chromosome DNA, increases the rate of cell divisions, and reduces
      the number of organelles per cell. The described changes in the number of
      chloroplasts are inherited in cell lineage ("cell hereditary memory") and
      successive sporophyte generations.

PMID- 15458205
TI  - [The roles of the NANA and LEPIDA genes in regulating the stem growth in
      Arabidopsis thaliana].
AB  - Genetic, physiological, and morphological studies of dwarf mutants of Arabidopsis
      thaliana (L.) Heynh. from the collection of the Department of Genetics and
      Breeding, Moscow State University, showed that the NA and LE genes are involved
      in regulating elongation of internode cells and sensitivity to various hormones.
      The na mutation suppressed stem growth only in the presence of the active LE
      gene. The absence of the LE activity (in the lele homozygote) restored stem
      growth of the na mutant to the level characteristic of the le-2 mutant, and a
      decrease in LE activity (in LEle heterozygote) almost completely suppressed the
      na phenotype. Phenotypic analysis of homozygous double mutants and heterozygotes
      obtained by crossing the na and le-2 mutants showed that the recessive le-2
      allele has an epistatic effect on the semidominant na allele and that the genes
      possibly control consecutive steps of one biochemical pathway or one
      morphogenetic process. A hypothetical scheme was proposed for the interaction of
      the NA and LE gene products.

PMID- 15458206
TI  - [Population-genetic structure of beaver (Castor fiber L., 1758) communities and
      estimation of effective reproductive size Ne of an elementary population].
AB  - The absence of panmixia at all hierarchical levels of the European beaver
      communities down to individual families implies a complex organization of the
      population-genetic structures of the species, in particular, a large intergroup
      component of gene diversity in the populations. Testing this assumption by
      analysis of 39 allozyme loci in the communities of reintroduced beaver from the
      Vyatka river basin (Kirov oblast) has shown that only the beaver colonies exhibit
      high intergroup gene diversity (Gst = 0.32) whereas this parameter is much lower
      when estimated among beaver groups from individual Vyatka River tributaries and
      among localities of one of the tributaries (0.07 and 0.11, respectively). The
      data suggesting genetic heterogeneity among individual settles within colonies
      have been obtained. The factors affecting the structure of the beaver communities
      of the lower hierarchical ranks are considered: the common origin, founder
      effect, selection, gene drift, assortative mating, and social and behavior
      features of the species. The conclusion is drawn that the founder effect could be
      the primary factor of population differentiation only at the time of their
      formation. The heterogeneity among colonies and among settles is maintained
      largely by isolation of colonies from one another. The strong interspecific
      competition for food resources, which is behaviorally implemented in the species
      at the level of minimal structural units (individual settles) creates a profound
      and unique population-genetic subdivision of the species. These results
      substantiate the suggestion that an elementary population (micropopulation) of
      European beaver is a colony, i.e., a set of related settles of different types.
      Based on ecological and genetic parameters, the effective reproductive size Ne of
      the minimum beaver population was estimated to be equal to three animals. This
      extremely low value of effective reproductive population size largely explains
      the high tolerance of European beaver to inbreeding and striking viability of the
      species, which from the early 19th century has been for more than hundred years
      on the brink of survival in the condition which would made any other mammalian
      species vanish from the Earth.

PMID- 15458207
TI  - [The structure of a conserved region of porcine genome, represented in human
      genome by chromosome 17].
AB  - Radiation mapping of nine genes (H3F3B, HLR1, MYL4, STAT5B, THRA1, TOP2A, MCP1,
      NF1, and MPO) to porcine chromosome 12 was carried out. Also, subchromosomal
      location of the NF1 gene along with the two loci containing the DNA sequences
      homologous to the DNA of the two human BAC clones was determined. The NF1
      position was ascertained via microdissection of chromosome 12 with subsequent PCR
      amplification of the gene fragment with specific primers. BAC clones were mapped
      using FISH. Comparative analysis of the gene order in porcine chromosome 12 and
      in the homologous human chromosome 17 was performed. It was demonstrated that the
      gene orders in these chromosomes differed relative to the position of the MPO
      gene.

PMID- 15458208
TI  - [The we gene is a modifier of the wal gene in mice].
AB  - Interaction of gene wellhaarig (we) with genes waved alopecia (wal) and hairless
      (hr) was studied in mice. The mutant gene we is responsible for the development
      of a specific waved coat in homozygotes. Homozygous mice carrying mutant gene wal
      also have a wavy coat, though a partial alopecia develops with time in these
      animals. In homozygotes for the hr gene, hair loss is observed beginning from the
      age of ten days. A series of crosses we/we and wal/wal yielded animals with
      we/+wal/wal and we/we wal/wal genotypes. In mice we/+wal/wal carrying gene we at
      a single dose, alopecia is accelerated significantly as compared to the single
      dose homozygotes +/+wal/wal. In we/we wal/wal mice, alopecia starts earlier than
      in we/+wal/wal mice; by the age of one month, the double homozygotes are almost
      hairless except for small body areas covered with a sparse coat. In addition,
      curliness of the first-generation hair in mice we/we wal/wal is much more
      expressed than in +/+wal/wal and we/we+/+ mice. The obtained evidence suggests
      that the we gene is a modifier of the wal gene because the former enhances the
      effects of the wal gene, which is confirmed by the earlier onset of alopecia and
      progression of the latter in mice having the we/+wal/wal genotype and especially
      in we/we wal/wal animals. The we/we hr/+ mice do not differ in coat from we/we+/+
      mice; in both cases, the coat is wavy. The coat of double homozygotes we/we
      hr/hr, is similar to that of we/we+/+ mice until ten days of age, when the signs
      of alopecia appear. By the age of 21 days, mice we/we hr/hr have lost their coat
      completely like mice +/+ hr/hr. Hence, the we gene is a modifier of the wal gene
      though it does not interact with hr gene during the coat formation.

PMID- 15458209
TI  - [Mitochondrial DNA variation in two Russian populations from Novgorod oblast].
AB  - Mitochondrial DNA (mtDNA) polymorphism was examined in two Russian populations of
      Novgorod oblast, from the city of Velikii Novgorod (n = 81), and the settlement
      of Volot (n = 79). This analysis showed that the mitochondrial gene pool of
      Russians examined was represented by the mtDNA types belonging to 20 haplogroups
      and subhaplogroups distributed predominantly among the European populations.
      Haplogroups typical of the indigenous populations of Asia were found in the
      population sample from Velikii Novgorod with the average frequency of 3.7%
      (haplogroups A, Z, and D5), and with the frequency of 6.3% (haplogroups Z, D, and
      M*) in the Volot population. It was demonstrated that the frequency of the
      mitochondrial lineages combination, D5, Z, U5b-16144, and U8, typical of the
      Finnish-speaking populations of Northeastern Europe, was somewhat higher in the
      urban population (7.4%) compared to rural one (3.8%). The problem of genetic
      differentiation of Russians from Eastern Europe inferred from mtDNA data, is
      discussed.

PMID- 15458210
TI  - [Maternal cell contamination of cultures of spontaneous abortion fibroblasts:
      importance for cytogenetic analysis of embryonic lethality].
AB  - The results of standard cytogenetic analysis of the long-term cultures of
      embryonic fibroblasts of 478 first-trimester spontaneous abortions were
      retrospectively reviewed. In 16% of embryos with cytogenetically confirmed
      karyotype 46,XX, the Y chromosome was found by molecular genetic methods. Prior
      to obtaining the chromosome preparations, the cell cultures of Y chromosome
      carrying embryos were maintained for a longer period than the cultures of embryos
      without the Y chromosome. Thus, a late entry of a culture into the logarithmic
      growth phase serves as marker of maternal cell contamination. We developed a
      mathematic model for assessment of karyotype incidence and the "sex ratio" of
      spontaneous abortions, taking into account risk of maternal cell contamination in
      extraembryonic tissue cultures. Thus estimated, the incidence of chromosomal
      abnormalities in the studied sample increased from 54.6 to 60.3% and the expected
      sex ratio increased from 0.66 to 1.02 in abortions with normal karyotype. Using
      molecular analysis of inheritance of polymorphic DNA markers of six autosomes (2,
      11, 16, 19, 20, and 21), the proposed model was tested on 60 embryos with
      karyotype 46,XX and their parents. Numerical chromosome abnormalities were
      revealed in uncultured tissues of seven abortions (11.7%), including four without
      the Y chromosome, which is in a good agreement with the expected incidence of
      karyotype abnormalities (8.3%) predicted by our model. In view of this,
      estimating risk of maternal cell contamination in embryonic cell cultures seems
      necessary for correctly assessing the effect of natural selection in humans, for
      understanding the mechanisms that determine the sex ratio, and for evaluating the
      precision of prenatal cytogenetic diagnosis of chromosomal abnormalities.

PMID- 15458211
TI  - [Effect of the 5R(5A) alien chromosome substitution on the growth habit and
      winter hardiness of wheat].
AB  - The growth habit, ear emergence time, and frost tolerance of wheat/rye
      substitution lines have been studied in cultivars Rang and Mironovskaya
      Krupnozernaya whose chromosome 5A is substituted with chromosome 5R of
      Onkhoyskaya rye. Hybrid analysis has demonstrated that the spring habit of the
      recipient cultivars Rang and Mironovskaya Krupnozernaya is controlled by dominant
      gene Vrn-A1 located in chromosome 5A. Onokhoyskaya rye has a dominant gene for
      the spring habit (Sp1) located in chromosome 5R. It has been found that the
      resultant 5R(5A) alien-substitution lines have a winter type of development and
      ears do not emerge during summer in plants sown in spring. The change in growth
      habit has been shown to be related to the absence of the rye Spl gene expression
      in the substitution lines. The winter hardiness of winter 5R(5A) alien
      substitution lines has been studied under the environmental conditions of
      Novosibirsk. Testing the lines in the first winter demonstrated that their winter
      survival is 20-27%. The possible presence of the frost resistance gene
      homeoallelic to the known genes Fr1 and Fr2 of the common wheat located on
      chromosomes 5A and 5D, respectively, is discussed.

PMID- 15458212
TI  - [The nucleotide sequence of the rep gene of cyanobacterial plasmid pSM1].
AB  - The nucleotide sequence was established for the rep gene of plasmid pSM1 isolated
      from cyanobacterium Plectonema boryanum CALU 465. Both nucleotide sequence and
      the encoded amino acid sequences showed 98% homology to the corresponding
      sequences of small plasmids pPF1, pGL3, pPBS1, pBLX, and pPB1. An active center
      was identified in the replicative protein sequences.

PMID- 15458213
TI  - [Polymorphism of the ND1 and CO1 mitochondrial genes in populations of liver
      fluke Fasciola hepatica].
AB  - Polymorphism of fragments of the ND1 and CO1 mitochondrial genes was for the
      first time found in four liver fluke Fasciola hepatica samples from Ukraine,
      Belarus, Moscow region, and Mordovia. The ND1 and CO1 fragments were respectively
      292 and 433 bp in size, with polymorphic sites accounting for 2.7 and 0.9% of the
      total sequence. Seven haplotypes were found in the four samples; two haplotypes
      (A and B) were most common (29.1 and 45.8%, respectively) in the pooled sample.
      The haplotype frequency distribution differed among the four populations.
      Haplotype B prevailed in the Mordovian and Moscow region samples. In addition,
      these samples had a higher number of unique haplotypes (A2, A3, B2). The results
      testify to genetic divergence of the four geographically distant populations of
      F. hepatica.

PMID- 15458214
TI  - [CAM research must be ethically justified. Same requirements for alternative
      medicine as for conventional medicine].

PMID- 15458215
TI  - [Oxytocin--biochemical link for human relations. Mediator of antistress, well
      being, social interaction, growth, healing...].

PMID- 15458216
TI  - [ST-segment elevation--a diagnostic problem. Thorough knowledge of the ST-segment
      is crucial for correct treatment].

PMID- 15458217
TI  - [High-dose immunoglobulin--life-saving in invasive group A streptococcal
      infection. Report of eleven cases with only one fatality].
AB  - Invasive group A streptococcal infection is an uncommon but severe disease.
      Bloodcultures usually yield growth of Streptococcus pyogenes and the bacteria may
      also be isolated from sterile sites e.g. muscle or pleura. The most serious
      manifestation is Streptococcal Toxic Shock Syndrome (STSS) with or without
      necrotizing fasciitis (NF). This condition may occur in about a fifth of the
      cases with a very high case-fatality rate. Preclinical data and case reports
      suggest that the fatality rate can be reduced by treatment of high-dose
      intravenous immunoglobulin. A European placebo-controlled clinical trial with
      immunoglobulin has been conducted but was prematurely terminated due to
      difficulties in patient recruitment. In our clinic we have during the last 3.5
      years seen 41 patients with invasive group A streptococcal infection and 11 of
      these have received high-dose immunoglobulin. The indication for that treatment
      has been hypotension and multiorgan failure. All 11 patients but one fullfilled
      the criteria for STSS and 5 had NF. Most of the patients were treated with a
      single dose intravenous infusion of 50 g immunoglobulin. All patients were
      treated with both benzylpenicillin and clindamycin. Ten patients were fully
      recovered--case-fatality rate 9 percent. We suggest that patients with invasive
      group A streptococcal infections who develop STSS with or without NF should be
      treated with high-dose intravenous immunoglobulin.

PMID- 15458218
TI  - [Perineal groove--an undiagnosed malformation?].
AB  - Perineal groove is a congenital malformation characterized by a red and wet
      groove in the perineum between the fourchette and the anus. It has been
      considered a rare malformation. We managed three patients with a perineal groove
      from July 1 2002 to July 1 2003. During that period we encountered approximately
      10 other new patients with various anorectal malformations. This indicates that
      perineal groove probably is a more common anomaly than previously reported. The
      anomaly requires no treatment. However, in one of our cases an associated anomaly
      of the urinary tract was found. We find it indicated to do an ultrasound of the
      urinary tract in patients with perineal groove.

PMID- 15458219
TI  - [Physicians report verbal drug information. Cases scrutinized by the IGM].

PMID- 15458220
TI  - [Insult--breeding ground for burnout. Employers "abuse" employee loyalty,
      according to an interview study].

PMID- 15458221
TI  - [Suez Channel and ductus choledochus. Biliary tract surgery with global political
      consequences].

PMID- 15458222
TI  - [Prosopagnosia--incapacity to recognize faces].

PMID- 15458223
TI  - [Heinrich Heine, tormented poet: "None of my doctors knows the cause of my
      suffering"].

PMID- 15458224
TI  - [Linguistics of gender medicine. Gene an important, generative morphem].

PMID- 15458225
TI  - [Support permanent discount for Viagra and Cialis in MS! Specified subsidy
      according to the Danish model is justified].

PMID- 15458226
TI  - [Achilles tendon injuries, sports medicine and ethics--learned lessons and
      conclusions].

PMID- 15458227
TI  - [Big differences between staffing agencies].

PMID- 15458228
TI  - [AC-laryngitis--a known disease or not?].

PMID- 15458229
TI  - An alternative evaluation method for swelling studies of bioadhesive tablet
      formulations.
AB  - A new and alternative evaluation method is preferred for swelling studies of
      bioadhesive tablet formulations. CIELAB color coordinates, related to visual
      color response, are used for the first time to follow the swelling state and to
      calculate the swelling volume. The results are evaluated statistically. A simple
      equation is given to explain the relation between the swelling volume change %
      and color difference for three different bioadhesive formulations. It was found
      that the estimated equation is in good agreement with observed swelling volume
      results.

PMID- 15458230
TI  - Effect of processing and formulation variables on the stability of a salt of a
      weakly basic drug candidate.
AB  - The effect of some processing and formulation variables on the stability of
      tablets containing a crystalline salt of a triazine derivative was studied. The
      salt has a relatively low melting point and a low microenvironmental pH due to
      the weakly basic nature of the parent compound (pKa = 4.0). This compound
      decomposes through acid-catalyzed hydrolysis. A full factorial design was used to
      study the effect of three variables on tablet stability: aqueous wet granulation,
      ball milling of the salt and filler prior to manufacturing, and the inclusion of
      sodium carbonate in the formulation as a pH modifier. In addition to the
      factorial design experiments, a batch of tablets was prepared by wet granulation,
      using sodium bicarbonate as the pH modifier. Stability of the drug in tablets was
      evaluated at 40 degrees C/75% relative humidity (RH) and at 40 degrees C/ambient
      humidity. Stability of tablets was adversely affected by wet granulation.
      However, stability was greatly improved by wet granulation in the presence of
      sodium carbonate. While sodium carbonate enhanced drug stability in the tablets,
      regardless of the manufacturing process, wet granulated tablets were more stable
      than tablets containing sodium carbonate and prepared without wet granulation.
      Similarly prepared tablets by using sodium bicarbonate were remarkably less
      stable compared with those containing sodium carbonate. The use of sodium
      bicarbonate as a pH modifier resulted in only marginal enhancement of tablet
      stability, suggesting that a higher microenvironmental pH than that provided by
      sodium bicarbonate is needed to maximize stability. Despite the low lattice
      energy of the salt and the potential for disruption of salt crystallinity by
      mechanical stress, milling did not appear to have an adverse effect on tablet
      stability under the current experimental conditions. This study shows that
      selection of the proper manufacturing process, in conjunction with the
      appropriate pH modifier, could be critical to dosage form stability.

PMID- 15458231
TI  - Prediction of drug dissolution from tablets using near-infrared diffuse
      reflectance spectroscopy as a nondestructive method.
AB  - The goal of this study is to use near-infrared (NIR) reflectance spectroscopy to
      measure the percentage drug dissolution from a series of tablets compacted at
      different compressional forces, calibrate NIR data vs. laboratory equipment data,
      develop a model equation, validate the model, and test the model predictive
      ability. Seven theophylline tablet formulations of the same composition but with
      different dissolution profiles were prepared. Laboratory dissolution profiles
      were compared with NIR diffuse reflectance data. Linear regression, quadratic,
      cubic, and partial least-square techniques were used to determine the
      relationship between dissolution profiles data and NIR spectra. The results
      demonstrated that a decrease in the amount of drug dissolution produced an
      increase in NIR absorbance. A series of model equations, depending on the
      mathematical technique used for regression, were developed from the calibration
      of the percentage of drug dissolution by using laboratory equipment vs. the NIR
      diffuse reflectance for each formulation. The results of NIR dissolution data
      were similar to laboratory tests. The NIR diffuse reflectance spectroscopy method
      is an alternative, nondestructive method for measurement of drug dissolution from
      tablets.

PMID- 15458232
TI  - Toward the development of an injectable dosage form of propofol: preparation and
      evaluation of propofol-sulfobutyl ether 7-beta-cyclodextrin complex.
AB  - The objectives of the present study were to undertake activities toward the
      development of an aqueous-based formulation of propofol (2,6-diisopropyl phenol),
      using sulfobutylether 7-beta-cyclodextrin (SBECD). Preformulation studies,
      including high performance liquid chromatography (HPLC) method development and
      phase-solubility evaluation in the presence of SBECD were conducted. It was
      determined that equilibrium solubility has been reached by 4-day and 7-day phase
      solubility analysis at 30 degrees C and 37 degrees C. The apparent binding
      constants and various thermodynamic parameters were calculated from this data.
      These results suggest that "nonclassical hydrophobic effects" are the driving
      forces for inclusion complex formation. Compounding and lyophilization of the
      formulation with 20% SBECD yielded a product with propofol concentration of 10
      mg/mL. The formulation properties were probed by using techniques that included
      modulated differential scanning calorimetry (MDSC) and Karl Fischer analysis.
      MDSC showed that propofol, SBECD, and the Propofol-SBECD complex displayed
      thermal properties at widely varying temperatures, suggesting the formation of a
      new solid form. The active pharmaceutical ingredient in the liquid formulation
      and lyophilized product was determined by the newly developed and qualified HPLC
      method. Short-term stability studies of the liquid formulation showed that they
      were stable for a month at 4 degrees C. Short-term stability studies of the
      freeze-dried cakes showed that the product was stable for over a month at 4
      degrees C, 37 degrees C, and 50 degrees C. Based on these preliminary results, we
      believe that an aqueous based injectable formulation of propofol with
      sulfobutylether 7-beta-cyclodextrin can be successfully developed.

PMID- 15458233
TI  - Topical liposomal gel of idoxuridine for the treatment of herpes simplex:
      pharmaceutical and clinical implications.
AB  - The optimization of the method of preparation of idoxuridine (IDU) liposomes by
      the reverse phase evaporation (REV) method was carried out by three variables at
      three levels (3(3)) factorial design. The three independent variables selected
      were volume of organic phase (x1), volume of aqueous phase (x2), and
      drug/phosphatidylcholine/cholesterol in molar ratio (x3). Twenty-seven batches of
      IDU liposomes were prepared by the REV method and subjected to evaluation for
      percentage drug entrapment (PDE), size, and size distribution. A reduced
      polynomial equation was derived by multiple regression of the data of PDE and the
      transformed values of the three independent variables. Three contour plots at
      fixed level of-- 1 (low), 0 (medium), and 1 (high) of major contributing variable
      (x3) were plotted between x1 and x2 at predetermined PDE to understand the
      physical meaning of independent variables. Liposomal gels were prepared by
      dispersing optimized IDU liposomes in 2%w/w and 5%w/w (HPMC) K4M gel bases so as
      to contain 1%w/w IDU (LIG-1 and LIG-2, respectively). The percentage of drug
      retention (PDR) studies of optimized batch 14 (Lipo-14) and LIG-1 and LIG-2 were
      carried out at three different storage conditions (2-8 degrees C, 25 +/- 2
      degrees C, and 37 degrees C). A comparative diffusion study of LIG-1 and LIG-2
      with PIG-1 and PIG-2 (1%w/w IDU with components of liposome dispersed in 2%w/w
      and 5%w/w HPMC K4M gel bases, respectively), respectively, through human cadaver
      skin was conducted. A comparative double blind clinical pilot study of optimized
      LIG-2 gel was carried out for eight weeks and compared with PIG-2 on 20 Herpes
      simplex patients (10 patients each for HSV-1 and HSV-2, divided into two groups
      each of 5 patients). Batch 14 (Lipo-14) was found to have maximum PDE of 74.4%.
      The PDR study showed maximum drug retention at 2-8 degrees C. A significant
      increase in PDR (p<0.05) was observed in LIG-1 and LIG-2 when compared with Lipo
      14 at all the three temperatures. In the diffusion studies, a significant
      (p<0.05) flux reduction; 3.5 times in LIG-1 when compared with PIG-1 and 2.3
      times in LIG-2 when compared with PIG-2 was observed. Approximately 2.2- and 2.5
      fold increase in skin drug retention in LIG-1 and LIG-2, respectively, was
      determined. A double blind clinical study demonstrated an approximately 2.0- and
      1.6-fold increase in average percentage improvement in healing of the lesions in
      patients suffering from HSV-1 and HSV-2 diseases, respectively, when treated with
      LIG-2 compared with PIG-2. However, complete removal of lesions was not observed.
      Local side effects such as itching, burning, inflammation in HSV-1 and HSV-2, and
      burning micturation in HSV-2 associated with the use of PIG-2 were reduced
      considerably with the use of LIG-2. The findings of this investigation establish
      the role of the derived equation and plotted contour plots in predicting the
      values of independent variables for preparation of IDU liposomes by the REV
      method. The study also demonstrated that IDU liposomal gels retain more drug when
      compared with plain liposomes at all temperatures for the period of three months,
      while maximum PDR was found at refrigeration temperature. The skin retention of
      IDU was enhanced due to its entrapment in the liposomal vesicles. The clinical
      study suggested the improvement of therapeutic efficacy of IDU entrapped in
      liposomes in treatment of HSV-1 and HSV-2 patients.

PMID- 15458234
TI  - Effect of process variables on particle size of gelatin microspheres containing
      lactic acid.
AB  - Gelatin microspheres containing lactic acid were prepared by a polymerization
      technique using glutaraldehyde as the cross-linking agent. Because particle size
      distribution of microspheres is a vital factor in the characterization of
      microspheres, the present study was carried out to evaluate the effect of process
      variables on the microspheres size distribution. It was found that concentration
      of a gelatin solution is the most important parameter that influences the
      particle size of microspheres. By using different concentrations of gelatin
      solution, microspheres with different size ranges were prepared. Both the
      stirring rate of the system and the volume ratio of aqueous and oil phases
      exerted a great influence on microsphere-size distribution, whereas, cross
      linking time and cross-linker concentration only affected the yield. Lower-phase
      volume ratios resulted in small uniform microspheres with smooth surfaces and a
      narrow size range. The effect of emulsifier concentration (span 80), below 1%
      (w/w, with respect to the weight of the oil phase), on particle size was
      appreciable. However, at higher concentrations, little effect was observed.

PMID- 15458235
TI  - Application of a mixture experimental design in the optimization of a self
      emulsifying formulation with a high drug load.
AB  - Response surface methodology (RSM) was applied to optimize the self-emulsifying
      drug delivery system (SEDDS) containing 25% (w/w) Drug A, a model drug with a
      high lipophilicity and low water solubility. The key objective of this study was
      to identify an optimal SEDDS formulation that: 1) possesses a minimum
      concentration of the surfactant and a maximum concentration of lipid and 2)
      generates a fine emulsion and eliminates large size droplets (> or = 1 microm)
      upon dilution with an aqueous medium. Three ingredient variables [PEG 400,
      Cremophor EL, and a mixture of glycerol dioleate (GDO), and glycerol monooleate
      (GMO)] were included in the experimental design, while keeping the other
      ingredients at a fixed level (25% Drug A, 6% ethanol, 3% propylene glycol, 4%
      water, and 2% tromethamine) in the SEDDS formulation. Dispersion performance of
      these formulations upon dilution with a simulated gastrointestinal fluid was
      measured, and the population of the large droplets was used as the primary
      response for statistical modeling. The results of this mixture study revealed
      significant interactions among the three ingredients, and their individual levels
      in the formulation collectively dictated the dispersion performance. The fitted
      response surface model predicted an optimal region of the SEDDS formulation
      compositions that generate fine emulsions and essentially eliminates large
      droplets upon dilution. The predicted optimal 25% Drug A-SEDDS formulations with
      the levels of Cremophor EL ranging from 40-44%, GDO/GMO ranging from 10-13%, and
      PEG 400 ranging from 2.7-9.0% were selected and prepared. The dispersion
      experiment results confirmed the prediction of this model and identified
      potential optimal formulations for further development. This work demonstrates
      that RSM is an efficient approach for optimization of the SEDDS formulation.

PMID- 15458236
TI  - Ion pair formation as a possible mechanism for the enhancement effect of lauric
      acid on the transdermal permeation of ondansetron.
AB  - Transdermal application can be an alternative drug delivery route for
      ondansetron, an antiemetic drug. Previous studies found that fatty acids, namely
      oleic and lauric, were the most effective penetration enhancers. The aim of this
      study was to investigate the formation of an ion pair between ondansetron and
      lauric acid as a possible mechanism of its enhancing action. Several techniques
      were used to reveal the formation of an ion pair complex. Partitioning
      experiments, where the n-octanol/water coefficient was measured, showed an
      increase in the distribution coefficient in the presence of the acid, possibly as
      a result of the formation of more lipophilic ion pairs between the charged
      molecules of ondansetron and lauric acid. Further evidence of complex formation
      between ondansetron and lauric acid, was gained from the 13C-nuclear magnetic
      resonance (13C-NMR) spectra of ondansetron, lauric acid, and their mixture (molar
      ratio 1:1). The NMR spectra revealed alterations to the magnetic environment of
      the carbon atoms adjacent to the ionized group, which are the carbonyl group of
      the acid and the nitrogen of the imidazole ring of ondansetron. This evidence
      substantiates the theory of ion pair formation. Finally, thermal analysis of the
      binary mixtures of ondansetron and lauric acid revealed the formation of an
      additional compound, with different melting point from pure ondansetron and
      lauric acid, which is thermodynamically favored.

PMID- 15458237
TI  - Bilayer tablets based on poly (epsilon-caprolactone) and polymethylmethacrilates
      as controlled-release systems for ruminants.
AB  - Rumen-stable devices ensure a protection of active ingredients against chemical
      degradation and bacterial fermentation processes that occur in the rumen. These
      systems should also provide postruminal bioavailability and controlled release of
      the active ingredient. The objective of this study was the preparation of bilayer
      tablets as rumen-stable delivery systems, designed for the oral administration of
      active ingredients (folic acid) to ruminants. The tablets are composed of two
      layers: layer A ("high-density layer") constituted by poly (epsilon-caprolactone)
      mixed with iron powder and characterized by sufficient density to avoid
      rumination; layer B ("release layer"), containing folic acid (25 mg), poly
      (epsilon-caprolactone) or polymethylmethacrylates (Eudragit RS and RL) designed
      to be rumen-stable and to target a controlled release of folic acid in the
      intestinal tract. In vitro rumen-protection tests were performed in buffer
      systems at pH 5.5 and pH 2.0, simulating a ruminal and abomasal environment, to
      verify the stability of bilayer tablets at these conditions. In vitro release
      tests were carried out in phosphate buffer at pH 7.4, to study the release
      behavior of the dosage forms in the intestinal environment. A preliminary in vivo
      test was carried out with radiographic images made after administration of the
      tablets to sheep, to evaluate their capacity to be retained in the reticulum
      rumen. The amount of iron powder used provides a density of about 2.3 g/cm3 to
      the whole tablet. The tablets having layer B constituted by poly (epsilon
      caprolactone) or Eudragit RS do not disintegrate in buffer media at pH 5.5 and pH
      2.0, and they are characterized by a sustained release at pH 7.4. Radiological
      preliminary tests show that these prepared bilayer tablets are able to be
      retained in the reticulum-rumen tract of the sheep.

PMID- 15458238
TI  - Poly-epsilon-caprolactone nanocapsules containing octyl methoxycinnamate:
      preparation and characterization.
AB  - This study investigates the different nanocapsules (NCs) made of poly-epsilon
      caprolactone (PCL) containing the lipophilic sunscreen Escalol 557 [octyl
      methoxycinnamate (OMC)] and analyzes the influence of nanoparticle-based systems
      on light-induced decomposition of the sunscreen agent. The NCs were designed and
      prepared by the solvent displacement method. Formulation parameters, such as the
      nature and volume of the organic and aqueous phase and the nature and
      concentration of the surfactants and polymer, have relevant implications on NC
      elaboration. We investigated the influence of several technological (stirring
      speed: 300-800 rpm) and formulation factors [polymer amount, 195-244.5 mg;
      surfactant, Tween 85 (Polysorbate 85), Montanox 80 (Polysorbate 80), and
      Synperonic PE/F68 (Poloxamer 188) as stabilizing agents; and volume of the
      organic phase, 20-30 mL of acetone] on the particle size and the OMC loading
      capacity of the formulations--encapsulation efficiency and yield. The sizes of NC
      obtained were in the range of 309 to 1042 nm, the encapsulation efficiencies
      ranged from 93.82% to 99.97%, and yields of NC encapsulation ranged from 48.12%
      to 86.28%. Of all the preset experimental conditions, Montanox 80, 30 mL of
      acetone, 244.5 mg of polymer, and a stirring speed of 350 rpm have been selected
      as the best in this experimental design study. The experimental conditions
      selected to obtain OMC-loaded NC of 374 nm resulted in a high entrapment
      percentage (97.52%) and yield (82.95%). The PCL nanoparticles loaded with OMC
      were effective in reducing light-induced degradation of the sunscreen agent.

PMID- 15458239
TI  - [Dinitrosyl iron complexes are endogenous signaling agents in animal and human
      cells and tissues (a hypothesis)].
AB  - The hypothesis was advanced that dinitrosyl iron complexes generated in animal
      and human cells and tissues producing nitric oxide can function as endogenous
      universal regulators of biochemical and physiological processes. This function is
      realized by the ability of dinitrosyl iron complexes to act as donors of free
      nitric oxide molecules interacting with the heme groups of proteins, nitrosonium
      ions, or Fe+(NO+)2 interacting with the thiol groups of proteins. The effect of
      dinitrosyl iron complexes on the activity of some enzymes and the expression of
      the genome at the translation and transcription levels was considered.

PMID- 15458240
TI  - [A stochastic model for the NMR analysis of the heteroassociation of biologically
      active aromatic molecules].
AB  - A stochastic model for the NMR analysis of the heteroassociation of two aromatic
      compounds was developed, which takes into account all physically possible
      reactions of association of molecules in solution. Expressions for calculating
      the experimentally observed proton chemical shift were obtained in the general
      form, and an algorithm for calculating the parameters of heteroassociation using
      the stochastic model was proposed. The effects of limitations of the basic and
      general models, as compared with the stochastic model, on the model parameters of
      the heteroassociation of various biologically active aromatic molecules was
      analyzed. It was shown that the basic model can be used with a sufficient degree
      of accuracy for systems with a relatively small contribution of heteroassociation
      reactions to the total dynamic equilibrium in solution, whereas the general model
      describes satisfactorily the parameters of heteroassociation practically for all
      systems studied.

PMID- 15458241
TI  - [The mobility of the side chains of His57 and other amino acid residues in the
      active center of chymotrypsin].
AB  - Using the "hard-sphere" atom-atom approximation with consideration of the
      available X-ray data, the possibility of free rotation of the side chain of His57
      residue in the active center of chymotrypsin was studied. It was shown that there
      is a significant rotational freedom of the imidazole ring on chi1 and chi2
      torsional angles. The rotation is accompanied by the movement of the side chains
      of Tyr94, Ile99 and Ser195 residues. It was assumed that the four residues act as
      movable parts of the motor of the enzymatic machinery. Amino acid residues that
      contact the cavity around the His57 imidazole ring were identified.

PMID- 15458242
TI  - [Spin diffusion in globular proteins: alpha-lactalbumin].
AB  - The structural properties of globular proteins analyzed by two different methods:
      high-resolution NMR and circular dichroism were compared. We established that the
      spin diffusion method shows changes in the secondary structure during the
      unfolding of the alpha-lactalbumin molten globule by urea. It was shown that the
      spin diffusion method is extremely effective in studies of interactions of water
      and denaturant molecules with the protein both in the native and the molten
      globule states.

PMID- 15458243
TI  - [Natural polymers according to NMR data: cross-relaxation in hydrated collagen
      macromolecules from two connective tissues].
AB  - Spin-lattice relaxation and cross-relaxation in oriented and randomly oriented
      collagen fibers from two connective tissues (15-month-old calf and 8-year-old
      steer) at a water content of 0.6 g H2O/g dry matter were studied. Collagens were
      chosen according to different numbers of covalent nonreducible cross-links, which
      increase during the life of the animal. The spin-lattice relaxation curves for
      all the collagens after a 180 degree-tau-90 degree pulse sequence were described
      by two exponential components. The dependences of two components of spin lattice
      relaxation time and their populations on the length of the 180 degree-pulse were
      obtained. On the basis of data of Goldman-Shen sequence and the two-phase model,
      the populations of proton fractions (p(w) and p(c)) as well as the rates of
      transfer of magnetization between water protons and collagen protons (k(w) and
      k(c)) were calculated. No significant difference between k(w) (k(c)) in oriented
      and randomly oriented fibers as well as in fibers with different cross-linking
      was found. The estimates of the cross-relaxation times for low cross-link
      collagen and high cross-link one were done. The correlation times of dipole
      dipole interactions for both connective tissues were calculated using the cross
      relaxation theory.

PMID- 15458244
TI  - [Thermal denaturation of oligomeric proteins: structural and functional
      modifications, the sequence of steps].
AB  - On the basis of literature and own experimental data changes in the structural
      and functional properties of some oligomeric proteins of the blood system
      (hemoglobin, lactate dehydrogenase, superoxide dismutase, catalase) exposed to
      the influence of temperature in a broad range were analyzed. The many-phase
      character of the temperature modification of protein molecules with different
      values of functional and kinetic parameters for each of revealed stages was
      discovered. At a critical temperature and at higher values, the dissociation of
      oligomeric proteins into separate subunits was shown to occur along with the
      typical "loosening" of the protein globule. It was shown that low-molecular
      components (subunits) can subsequently associate with one another and with
      oligometic proteins, which leads to irreversible denaturation and to the unusual
      physicochemical behavior of protein molecules. Schemes of processes underlying
      the temperature modifications of the proteins studied were elaborated.

PMID- 15458245
TI  - [The interaction between two charged rods in an electrolyte solution].
AB  - A problem on the electrostatic interaction of two homogeneously charged
      macromolecular rods of a finite length, submerged into an electrolyte solution
      was considered. An explicit expression for the energy of interaction and
      rotational moment as a function of the angle of rotation between the long axes of
      the molecules was obtained. At small angles of rotation, the expression for
      energy turns into the corresponding formula for parallel rods, and the rotational
      moment tends to zero, as it follows from geometrical considerations. The
      possibility is discussed whether the study is applicable to real biological
      systems, including liquid-crystalline dispersions of DNA.

PMID- 15458246
TI  - [Mixed monolayers of amphiphile-modified nucleic bases and diynoic acids. I.
      Phase states at air-water interface and in Langmuir-Blodgett films].
AB  - Monolayers of amphiphile-modified nucleic bases with diynoic acid were obtained
      and characterized. The synthesized nucleic bases contained in the monolayer
      complementarily bind the nucleotide molecules contained in the aqueous subphase,
      and the structure of the resulting monolayers can be fixed by the
      photopolymerization of diynoic acid. The resulting monolayer exemplifies a novel
      type of model systems for investigating molecular recognition at the surface of
      biological membranes. Procedures for the transfer of the monolayers onto solid
      substrates and photopolymerization of the diynoic acid in mixtures with the
      derivatives of nucleic bases were developed. The films obtained were structurally
      characterized using atomic force microscopy. Compression isotherms of the mixed
      monolayers as well as individual components of monolayers at the air-water
      interface allowed one to determine the concentration range at which the diynoic
      acid form true mixtures or domain structures with the derivatives of nucleic
      base. A study of the films transferred to the solid substrate by atomic force
      microscopy indicated that this concentration dependence of miscibility behavior
      was conserved in the transferred films.

PMID- 15458247
TI  - [Photovoltaic behavior of chlorophyll a and beta-carotene in Langmuir films].
AB  - The photovoltaic properties of chlorophyll a and beta-carotene Langmuir films and
      Langmuir films of a mixure of chlorophyll a and beta-carotene at different molar
      ratios were investigated. SnO2-optically transparent electrodes were used as a
      support. It was shown that the film photovoltage value depends on surface
      pressure and the total film thickness (the number of layers deposited onto SnO2
      optically transparent electrodes). Fifteen layers (SP = 35 mH/m) of chlorophyll
      and 7-10 layers (SP = 20 mH/m) of beta-carotene give rise to a maximal
      photovoltage of 140 and 270 mV (at a shunt resistance of 10(7) Ohm),
      correspondingly. It was found that the photovoltage values in films of the
      carotene-chlorophyll mixture increase with the carotene concentration. The
      photovoltage value of a film containing 80-90% of carotene exceeds that of single
      component pigment films prepared under the same deposition conditions.

PMID- 15458248
TI  - [A discrepancy between the experimental and theoretical data on energy migration
      from B800 to B850 in LH-2 antennary complexes in purple bacteria].
AB  - A discrepancy between the times of excitation transfer from B800 to B850
      bacteriochlorophyll fractions in LH-2 complexes of purple bacteria was revealed.
      The experimental value (0.7-0.8 ps from literature sources) are at least four
      times lower than that (> 3.2 ps) calculated theoretically on the basis of
      recently obtained atomic structure of LH2. Possible reasons for this discrepancy
      are discussed.

PMID- 15458249
TI  - [The interaction of ferritin and myoglobin as inductors of lipid peroxidation.
      The role of reactive oxygen and nitrogen species].
AB  - The effect of iron dinitrosyl complexes, S-nitrosoglutathione, and glutathione on
      free radical oxidation of rat heart mitochondria induced by tert-butyl
      hydroperoxide and metmyoglobin or their combination with ferritin was studied. It
      was shown that iron dinitrosyl complexes or the combination of S
      nitrosoglutathione and glutathione inhibited most effectively the peroxidation of
      mitochondrial membranes. It was found that ferritin stimulated the prooxidant
      action of metmyoglobin. Using EPR spectroscopy, it was established that, in
      conditions of O2*- generation, the destruction of iron dinitrosyl complexes took
      place. Iron dinitrosyl complexes also inhibited the formation of thiyl radicals,
      which appeared during O2*- generation in the system containing glutathione and S
      nitrosoglutathione. It is essential that the formation of iron dinitrosyl
      complexes in this reaction system took place with the involvement of ferritin. It
      was proposed that the prooxidant action of ferritin and myoglobin could be
      inverted to the antioxidant one.

PMID- 15458250
TI  - [Structural changes in lipid membranes and collagen irradiated with UV light and
      the protective effect of plant extracts].
AB  - The results of experimental studies on the effect of UV irradiation on collagen,
      artificial lipid membranes, and rat skin, as well as the protective effect of
      plant extracts from UV radiation are presented. The irradiation of collagen and
      lipid membranes with solar and artificial UV light leads to structural changes in
      these objects. In particular, collagen molecules denature and transfer into a new
      conformational state. The effect of UV light on lipid membranes and liposomes
      leads to a disturbance of membrane structure, which is connected with a decrease
      in the number of lipid molecules involved in the cooperative transition from gel
      into a liquid crystal state. The components of plant extracts (mainly flavonoids)
      absorb UV radiation in the erythem-forming spectral area and block the
      destructive processes occurring in collagen and lipids.

PMID- 15458251
TI  - [The incorporation of rifampicin into multilayer and monolayer vesicles
      (liposomes) of different phosholipid composition].
AB  - The incorporation of rifampicin into multilayer phospholipid vesicles depending
      on the concentration of antibiotic and phospholipid content was studied. The
      extent of incorporation of rifampicin into monolayer vesicles (liposomes),
      obtained by the homogenization of multilamellar vesicles, was determined by the
      method of gel filtration. It was found that rifampicin better penetrates and is
      retained in membranes consisting of a mixture of phosphatidylcholine and
      cardiolipin, the maximum incorporation of rifampicin into liposomes being 17%. It
      was shown by 31P NMR spectroscopy that, during the interaction of rifampicin with
      the phospholipid membrane, the bilayer packing of phospholipids is destroyed.

PMID- 15458252
TI  - [Nonspecific effect of morphine on the erythrocyte membrane].
AB  - The effect of low morphine concentrations on the plasmatic membranes of
      erythrocytes without opiate receptors was investigated. It was shown that the
      ATPase activity and hemolytic stability of erythrocytes, which characterize the
      state of cell membranes and the mobility of the near-membrane water phase, depend
      on the concentration of morphine, and this dependence is wave-like. The
      nonmonotonous dependence of the biological response was suggested to be due to
      changes in the structure of water hydrogen links near the membrane surface,
      induced by opiate molecules. The hypothesis was confirmed by the results of
      studies of morphine water solutions using the methods of fluorescent probe and
      light scattering. It was found that the intensity of light scattering by water
      and the mobility of its molecules considerably increase in the presence of
      strictly specified concentrations of morphine.

PMID- 15458253
TI  - [Changes in lipid asymmetry and transport of glutathione conjugates under the
      influence of calcium ions in human erythrocytes].
AB  - The influence of calcium ions on the distribution of the fluorescent analog of
      phosphatidylcholine 2-(6-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoyl-1
      hexadecanoyl-sn-glycero-3-phosphocholine (C6-NBD-PC) in membranes and transport
      of glutathione-S-conjugates in human erythrocytes was studied. It was supposed
      that both processes were performed by the multidrug resistance protein. It was
      found that the increase in intracellular calcium concentration tended to both the
      redistribution of about 35% of C6-NBD-PC in the inner layer of the membrane and a
      decrease in the exit of glutathione-S-conjugates from erythrocytes. In both
      cases, the intracellular calcium concentration varied in the physiological
      (nanomolar) range. The results testify that Ca2+ participates in the regulation
      of the activity of the multidrug resistance protein.

PMID- 15458254
TI  - [Effect of cadmium on the absorption and excitation energy transfer in
      cyanobacterium Nostoc muscorum].
AB  - The absorption and energy transfer between pigments in Nostoc muscorum by the
      action of 10(-4) M Cd2+, when the cyanobacterium remains viable, and in the
      presence of 10(-3) M Cd2+, which causes the death of cells during 3-4 weeks of
      incubation, were studied. A comparative study by the methods of absorption and
      fluorescence spectrophotometry at 295 and 77 K, including derivative spectroscopy
      and deconvolution of emission spectra into a number of Gaussian components,
      showed that, in the presence of 10(-4) M Cd2+, the energy transfer from
      phycobilisomes to chlorophyll of photosystem I increased. After incubation with
      10(-3) M Cd2+, the energy transfer from phycobilisomes to chlorophyll of
      photosystem II decreased, and the transfer to photosystem I was absent. New bands
      in the absorption spectra, in the second derivative of absorption spectra, and in
      the fluorescence spectra at 77 K of cyanobacterium were observed after 7 days of
      incubation with cadmium. We belive that these bands are due to the formation of
      CdS particles and Cd-pigment complexes. The conclusion about the dual effect of
      Cd2+ on the functioning of the energy transfer chain in N. muscorum was derived.

PMID- 15458255
TI  - [An efficient way for obtaining transformants of Chlamydomonas reinhardtii by
      electroporation].
AB  - The cells of mutant CW-15, which does not form the cell wall, were transformed by
      electroporation. It was found that the transformation was optimal at a suspension
      density of 10(6) cells/ml in the middle of the logarithmic growth phase at a
      field intensity of 1 kW/cm and pulse duration 2 ms. It was shown that, under
      these conditions, the efficiency of transformation reached 10(3) HygR-clones per
      10(6) recipient cells. Exogenic DNA integrated into the genome of the nucleus of
      Ch. reinhardtii was inherited constantly for more than 350 generations; however,
      the tolerance to hygromycin appeared as an unstable feature. The advantages of
      using mutant CW-15 and the selective system to study the transformation of Ch.
      reinhardtii by heterologous genes are discussed.

PMID- 15458256
TI  - [A computer method for the evaluation of Paramecium motor activity using video
      records of their movement].
AB  - A method for the evaluation of Paramecium caudatum motility was proposed as a
      tool for the investigation of magnetobiological as well as other physical and
      chemical effects. The microscopically observed movement of paramecia is recorded
      and processed using a special software program. The protozoan motility is
      determined as a function of their mean velocity in a definite time. The main
      advantages of the method are that it is easily modified for determining various
      characteristics of the motor activity of paramecia and that the video data
      obtained can be reused.

PMID- 15458257
TI  - [Cryopreserved neurons of a mollusc are capable of morphological differentiation
      in culture in vitro].
AB  - It was shown in culture in vitro that neurons isolated from the cryopreserved
      brain of adult molluscs Lymnaea stagnalis L. retain viability. Isolated brains
      were frozen in liquid nitrogen vapors at a rate of 400-500 degrees C/min in the
      presence of 2 M dimethylsulfoxide. The samples were then plunged into liquid
      nitrogen and stored from 1 month to 2 years. Upon thawing and removing the
      cryoprotectant, the neurons were isolated from the brain and then introduced into
      a cellular culture in vitro. It was shown that the thawed neurons were capable of
      regenerating new nerve processes similar to those formed by unfrozen neurons in
      the control.

PMID- 15458258
TI  - [Investigation of the significance of correlation of fish electrical activity and
      electrotelluric field].
AB  - The data of digital measurements of electrical activity of weakly electric fish
      and electrotelluric field were studied. The duration of the time series was 4
      years. The identity of the spectral composition of the series analyzed and a
      rather strong correlation between them were found. The evaluation of significance
      of the correlation was made by a number of pairs of data values and by comparison
      of the correlation coefficients between the initial series with corresponding
      correlation coefficients between the same series after the following operations
      with them: 1) ranging; 2) filtration of trends; 3) filtration of the seasonal
      component; 4) division into sections. All tests and the identity of the compared
      series spectra convincingly confirmed the validity of the working hypothesis on
      probable existence of physically stipulated causal relations between the
      processes considered. However, numerical model experiments considering the
      flicker-noise character of the series demonstrated no less convincingly that the
      rather high correlation coefficient may be explained by the alternative
      hypothesis on the independence of the processes analyzed. Since the very wide
      range of different natural processes has a flicker-noise structure, the
      methodological significance of the results obtained is far beyond the limits of
      the specific problem of the present paper.

PMID- 15458259
TI  - [The underwater and airborne horizontal localization of sound by the northern fur
      seal].
AB  - The accuracy of the underwater and airborne horizontal localization of different
      acoustic signals by the northern fur seal was investigated by the method of
      instrumental conditioned reflexes with food reinforcement. For pure-tone pulsed
      signals in the frequency range of 0.5-25 kHz the minimum angles of sound
      localization at 75% of correct responses corresponded to sound transducer azimuth
      of 6.5-7.5 degrees +/- 0.1-0.4 degrees underwater (at impulse duration of 3-90
      ms) and of 3.5-5.5 degrees +/- 0.05-0.5 degrees in air (at impulse duration of 3
      160 ms). The source of pulsed noise signals (of 3-ms duration) was localized with
      the accuracy of 3.0 degrees +/- 0.2 degrees underwater. The source of continuous
      (of 1-s duration) narrow band (10% of c.fr.) noise signals was localized in air
      with the accuracy of 2-5 degrees +/- 0.02-0.4 degrees and of continuous broad
      band (1-20 kHz) noise, with the accuracy of 4.5 degrees +/- 0.2 degrees.

PMID- 15458260
TI  - [UHF-dielectrometry in the assessment of the structural organization of salt
      solutions and interstitial fluids in normal and cicatricial tissues].
AB  - The complex dielectric permittivity of salt solutions with positive and negative
      salvation as well as healthy and cicatricially changed human skin in situ at the
      frequencies of 42 and 56.6 GHz was measured. The relation between the dielectric
      characteristics of water and diluted salt solutions and changes in their
      structural organization conditioned by different temperatures of samples and the
      type of salvation of electrolytes was studied. The differences in the dielectric
      characteristics of healthy and cicatricially changed skin are interpreted in
      terms of the dependence of the structural organization of interstitial fluids on
      the morphological and functional state of biological tissues.

PMID- 15458261
TI  - [Biophysical concept of the human autodiagnostic system].
AB  - A possible neurophysiological mechanism of the therapeutic effect of weak
      influences was proposed, which is based on the following assumptions: 1. In the
      organism, there is an autodiagnostic system, which serves for the accumulation
      and processing of information on the state of the organs to diagnose a desease.
      2. The autodiagnostic disease is a recognizing system, i. e., a neuronet, which
      is constructed and functions according to the paradigms of neurocomputing. 3.
      Systemic (psychosomatic) diseases appear to result from erroneous diagnosis due
      to the defects of the autodiagnostic system. The influence of puncture on
      biologically active points corrects these defects, providing a positive
      therapeutic effect. A theoretical model for the structure and functioning of the
      autodiagnostic system is discussed. It is shown that the structure of the model
      autodiagnostic system coincides with that of Rexede plates forming the gray
      substance of the spinal cord. The experimental data on Rexede plates and their
      connections with organs and corresponding biologically active points are
      discussed. A relationship between the concept of the autodiagnostic system and
      the basic principles of alternative eastern medicine is discussed. It is shown
      that the Chinese model of puncture therapy represents a verbal description of the
      topological features of the phase space of the mathematical model for the
      recognizing neuroprocessor.

PMID- 15458262
TI  - [The wavelet analysis at heliobiological connections].
AB  - The Wavelet analysis of the time series of the number of insults per day and the
      variations of heliogeophysical indices was carried out. The patterns of Wavelet
      coefficients for both processes show a complex nonstationary behavior and the
      presence of periodic and acyclic constituents on different scales. During
      heliogeophysipal disturbances, the energy contribution to the processes increases
      more than threefold compared with the mean value on scales from three to five
      days.

PMID- 15458263
TI  - [The influence of the potential dependence of the amplitude of postsynaptic
      potentials on rhythmic processes of bioelectric activity of the cerebral cortex].
AB  - The dependence of the postsynaptic potential amplitude on the membrane potential
      was entered into the earlier derived integral equations describing the
      interactions between excitatory and inhibitory populations of neocortical
      neurons. The influence of the potential dependence on steady states and the
      stable region of oscillations of the mean membrane potential of neurons were
      investigated. Encephalograms of humans and animals in different functional states
      were numerically simulated. The real form of a power spectrum of
      electroencephalogram was obtained. The occurrence of the nonregular spindle
      shaped activity was revealed, which expands the frequency of basic oscillations
      and widens the spectral peak. In the unsteady region, the existence of a limiting
      cycle and the possibility of arising of the pathological activity observed upon
      abnormal brain functioning were shown with the help of the numerical nonlinear
      analysis.

PMID- 15458264
TI  - [Physiological basis of a possible increase in the efficacy of the photo- and
      magnetotherapy of the visual nerve upon partial atrophy and ischemia].
AB  - An approach to the choice of the parameters of physiotherapeutic and biophysical
      influence on the visual nerve was proposed. The approach is based on parallel
      photo- and magnetostimulation of excitable fibers in which the morphological and
      electrophysiological properties of fibers and some parameters of the pathological
      processes associated with partial artophy and ischemia are taken into account. A
      method for correlating the photostimulation by light flashes (intensity 65 mWt at
      emission wavelength 660 nm) of a portion of the retina with the choice of the
      parameters of magnetic influence (amplitude 73 mT, duration of the wave front of
      40 ms, and frequency of pulse sequence of about 1 Hz) on the visual nerve was
      developed.

PMID- 15458265
TI  - [A model of the neuronal network using eye micromovements for distinguishing
      contrasts on an image].
AB  - A monochromatic model of a neuron network of foveal retina with the straight way
      of information stream of the system "cone-diminutive bipolar-diminutive ganglion
      cell" is proposed. The network can distinguish contrasts on an image. It is shown
      that cells of the output level have concentric receptive fields formed due to eye
      micromovements. The paper discusses the functioning of the model in the case when
      eye movements contain resetting microsaccades as well as drift. A special
      attention is paid to the compensation of transient processes.

PMID- 15458266
TI  - [The expected nucleotide sequence of the human genome should be shortened about
      twofold].
AB  - The sizes of nucleotide sequences of chromosomes 21 and 22 of the human genome
      established in three independent laboratories were compared with the sizes
      expected from the accurately determined contribution of these chromosomes to the
      genome mass. It was found that the expected haploid mass of the genome is about
      twofold smaller than the lowest of the figures published. This strongly
      contradicts the current notions about the genome size. With the bineme model of
      chromosome, the expected overall length of the human genome is close to 2100 Mbp
      and the haploid mass is close to 4200 Mbp. According to the calculations
      performed, the bineme chromosome structure enhances the reliability of the genome
      about 1.6 x 10(8)-fold (the computations are given in the paper).

PMID- 15458267
TI  - [Organizational and methodological approaches to using digital X-ray fluorography
      in the diagnosis of lung diseases in practical public health care of the Russian
      Federation].
AB  - On the basis of a great body of information, the authors propose the most
      reasonable and effective organizational and methodological approaches to further
      actively introducing digital lung fluography into Russia's practical public
      health care. The paper discusses a diversity of topical problems associated with
      the practical use of digital X-ray fluorography (DXF), such as the assessment of
      its use depending on the level (municipal or regional) of public health care,
      methodological issues of its performance, current relationships of DXF and film
      fluorography; a place of DXF in the screening and routine clinical diagnosis of
      lung diseases. Great emphasis is laid on the role of DXF in the diagnosis of
      tuberculosis and cancer of the lung. The place and role of Russian manufacturers
      of digital lung fluorographs in the further development of SXF in practical
      public health care of Russia are also touched upon. The authors emphasize that
      replacement of film fluorography by digital one will present difficulties if
      regional and municipal health administrators do not take an active part in this
      matter.

PMID- 15458268
TI  - [Procedure for visualization of carbonic materials in maxillofacial surgery by
      spiral computed tomography].
AB  - The paper considers whether carbonic materials whose contrasting is achieved when
      they contain 8-12% of metallic boron power may be applied to restore bone defects
      of the facial skull. Implants of this composition were employed to operate on 4
      patients with different defects of the facial skull. A three-projection of SCT
      image obtained in the "SOFT" mode was used as a way of registration. The results
      of the studies have indicated that the materials under study have X-ray contrast,
      a complete biological compatibility, and non-toxicity when they are used in
      clinical practice.

PMID- 15458269
TI  - [Standardizing a protocol of magnetic resonance imaging of temporomandibular
      joints. Part I].
AB  - The paper presents the standard of a procedure for magnetic resonance imaging of
      temporomandibular joints, which has been used to examine 275 patients. It
      describes the study projections, that are most significant for visualization, and
      scanning protocols. Illustrations of magnetic resonance imaging of the structures
      of the intact temporomandibular joint are presented.

PMID- 15458270
TI  - [Some problems of radiation diagnosis of colon cancer].
AB  - The paper gives the view of the author who is based on his many-year experience
      in studying a role of radiation diagnosis of colon cancer. It shows it necessary
      to enhance the significance of radiation diagnosis. More attention should be
      given to the traditional section on the current radiation study of the large
      bowel: to irrigoscopy and single double contrasting. By taking into account the
      labor-consumption of irrigoscopy, the author suggests that the procedure should
      be simplified without losing its diagnostic capacities. However, he considers
      single double contrasting of the bowel to be the optimum technique of traditional
      X-ray study of the bowel in detecting its tumors. Pneumocolonoscopy and iliocecal
      node study of the ileocecal angle are given in the paper as supplementary
      techniques of traditional X-ray study of the large bowel. Emphasis is also placed
      on the role of radiation diagnostic techniques, such as ultrasound diagnosis, X
      ray computed tomography, and magnetic resonance imaging. By highly appreciating
      their significance in the diagnosis of colon cancer, the author believes that
      they should play a role of important, but additional ways of detecting this
      pathology. By pointing out the excellent capacities of fibrocolonoscopy, as
      applied to the problem discussed in the paper, the author does emphasize the
      certain limitations of this technique, by taking into account that its
      application can cause some complications. The author's opinion that the obvious
      increase in the incidence of endophytic carcinomas drastically enhances the role
      of their radiation diagnosis, but by obligatorily correcting currently available
      principal methodic and semiotic directives, runs through the entire paper.

PMID- 15458271
TI  - [Intravascular repair in extended arterial occlusive lesions (a preliminary
      communication)].
AB  - Subintimal recanalization as a procedure of percutaneous vascular repair is under
      study now. The Regional Clinical Hospital has performed 10 procedures of
      subintimal angioplasty in patients with extended total occlusions of iliac and
      femoral arteries. All the patients had presented with critical ischemia of the
      lower extremities with the mean humeromalleolar index of 0.24+/-0.08. A technical
      success was achieved in 8 patients in whom the mean humeromalleolar index was
      0.37+/-0.09. There were no procedure-associated complications.

PMID- 15458272
TI  - [Artificial contrasting of the hip joint in children and adolescents: X-ray
      anatomic study].
AB  - The diagnostic capacities of currently available radiation diagnostic techniques
      in imaging some anatomic structures of the hip joint (HJ) were determined on the
      basis of studies of 70 sectional sets of HJs in children and adolescents aged 0
      to 13 years through X-ray and anatomic comparisons. Magnetic resonance imaging
      (MRI) is the method of choice in visualizing the cartilaginous and soft-tissue
      structures of HJ in children and adolescents. MR-arthrography extends the
      capacities of the technique in imaging the articular surfaces and intraarticular
      structures of the joint. Contrast enhancement of the HJ cavity during X-ray study
      and computed tomography may be an alternative to MRI as it makes it possible to
      well visualize the cartilaginous head of the femur, the cartilaginous borders of
      the cotyloid cavity, the limbus, etc. Double contrasting enhances the capacities
      of detailed imaging of the articular surfaces, intraarticular structures,
      capsules, and ligamentous apparatus of HJ. The studies performed have specified
      the time course of anatomic changes during HJ growth and defined the method of
      choice or an alternative procedure of radiation techniques in the diagnosis of
      these changes, which is of great importance for early detection of pathological
      changes and for choice of therapeutic and diagnostic policy.

PMID- 15458273
TI  - [Optic coherent tomography: a new high-resolution technology of visualization of
      tissue structures. Communication II. Optical images of benign and malignant
      entities].
AB  - This is the second communication of a series of publications on Russian studies
      in the field of optical coherent tomography (OCT), the newest noninvasive highly
      resolving technology of visualization of the structure of biological tissues. By
      using the investing tissues as an example, this paper demonstrates the universal
      types of changes in their optical properties. Optimal images permit differentiate
      benign and malignant processes with a high degree of diagnostic accuracy. Diverse
      benign processes occurring in the epithelium are detected on the OCT images as
      changes in its height, the scattering properties and stroke of a basilar
      membrane. The absence of any structure on the image is the main OCT criterion for
      malignancy. The diagnostic efficiency of OCT is high in recognizing neoplasia of
      various mucous membranes: the sensitivity of the technique is 77-98%; its
      specificity and diagnostic accuracy are 71-96 and 81-87%, respectively.

PMID- 15458274
TI  - [Radiation and endoscopic diagnosis of a rare malformation of the intermediate
      bronchus].

PMID- 15458275
TI  - [The 80th anniversary of the Russian Research Center of X-ray Radiology, Ministry
      of Health of the Russian Federation].

PMID- 15458276
TI  - Effects of n-3 fatty acids on serum interleukin-6, tumour necrosis factor-alpha
      and soluble tumour necrosis factor receptor p55 in active rheumatoid arthritis.
AB  - We investigated the effects of a low n-6 fatty acid (FA) diet supplemented with
      fish oil on serum pro-inflammatory cytokine concentrations and clinical variables
      in patients with active rheumatoid arthritis (RA). Sixty patients were randomly
      assigned to receive a diet low in n-6 FAs and n-3 FAs supplement (fish oil
      group), a diet low in n-6 FAs and placebo (placebo group), or no special diet or
      intervention (control group). Serum cytokines and clinical and biochemical
      variables were evaluated at baseline and various timepoints. At week 18 the fish
      oil group had significant reductions in linoleic acid, C-reactive protein (CRP)
      and soluble tumour necrosis factor receptor p55 (sTNF-R p55), and significant
      elevations in eicosapentaenoic acid and docosahexaenoic acid compared with
      baseline. There were no significant differences in the clinical variables between
      the three groups. At week 24 there were significant reductions in interleukin-6
      and TNF-alpha in the fish oil and placebo groups. Supplementation with n-3 FA and
      a low n-6 FA intake decreased serum sTNF-R p55 and CRP levels in patients with
      RA.

PMID- 15458277
TI  - Expression of c-erbB-2 and p53 in breast carcinoma patients: comparison with
      traditional prognostic factors and survival.
AB  - We aimed to determine the correlations between standard clinicopathological
      factors and expression of c-erbB-2 and p53 proteins, and to investigate the
      significance of these variables in relapse and disease-free survival (DFS) in
      breast carcinoma patients. Data from 200 patients who had undergone mastectomy
      for breast carcinoma were evaluated. Significant correlations were found between
      c-erbB-2 positivity and high histological grade (grade 3) tumour, p53 positivity
      and high grade tumour, and age < 60 years and oestrogen receptor negativity.
      Twenty-six patients (13%) developed a recurrence. Disease relapse was more
      frequent in patients who had axillary lymph node (ALN) metastasis, high grade
      tumour, c-erbB-2 positivity and p53 positivity; these variables were also
      associated with a shorter DFS. The effects of ALN metastasis and p53 positivity
      were significant. In conclusion, ALN metastasis and p53 positivity were important
      factors for predicting disease relapse in mastectomy-treated breast carcinoma
      patients; other clinicopathological criteria and c-erbB-2 positivity were not
      predictive.

PMID- 15458278
TI  - beta2-adrenergic receptor stimulation-induced immunosuppressive effects possibly
      through down-regulation of co-stimulatory molecules, ICAM-1, CD40 and CD14 on
      monocytes.
AB  - We examined the effects of beta2-adrenergic receptor (beta2-AR) agonists on the
      expression of co-stimulatory molecules on lipopolysaccharide (LPS)-stimulated
      human peripheral blood mononuclear cells. The study found that beta2-AR agonists
      inhibited the expression of intercellular adhesion molecule-1 (ICAM-1), CD40 and
      CD14 on monocytes, and that AR agonist activity was antagonized by the selective
      beta2-AR antagonist, butoxamine. The selective beta2-AR agonists salbutamol and
      terbutaline induced a similar co-stimulatory molecule expression pattern. The LPS
      induced production of tumour necrosis factor-alpha was inhibited by AR agonists,
      and this was also antagonized by butoxamine, and mimicked by salbutamol and
      terbutaline. The AR agonists also inhibited T-cell proliferation through beta2-AR
      stimulation. This study clearly demonstrated that endogenous catecholamines
      elicited immunosuppressive effects through beta2-AR stimulation, possibly due to
      down-regulation of the expression of ICAM-1, CD40 and CD14 on monocytes. These
      results suggested that the sympathetic nervous system might regulate the T-helper
      cell balance via the peripheral end-effectors of the stress system.

PMID- 15458279
TI  - Rapid identification of the Candida species from direct blood cultures by
      CHROMagar Candida.
AB  - We evaluated the ability of CHROMagar Candida to identify Candida species
      isolated directly from blood cultures. A total of 50 clinical isolates of Candida
      were incubated at 35 degrees C, and once growth was established, an aliquot of
      each was plated onto CHROMagar Candida medium. A control specimen was plated
      directly from Sabouraud's dextrose agar. Following incubation at 30 degrees C,
      all yeast isolates were identified by colony morphology and colour. We were able
      to identify all isolates of C. albicans (n = 20), C. tropicalis (n = 14), C.
      glabrata (n = 6), and C. krusei (n = 5), which were isolated from blood or from
      control cultures. This study demonstrated that CHROMagar Candida reliably
      isolated and identified yeast taken directly from blood cultures. We conclude
      that this rapid and easy method of identifying Candida species will enable
      clinicians to quickly choose the appropriate antifungal agent. This should
      decrease patient morbidity and mortality.

PMID- 15458280
TI  - Effect of anti-cancer drugs on the binding of 125I-Fibrinogen to two leukaemia
      cell lines in vitro.
AB  - Anti-cancer drugs may be able to inhibit tumour growth and metastasis by blocking
      fibrinogen- and/or fibrin-related pathways. To test this hypothesis, the effect
      of various anti-neoplastic drugs on the binding of 125I-Fibrinogen to two
      leukaemia cell lines, HL60 and P388, was investigated. All the drugs tested
      inhibited the binding of fibrinogen to leukaemia cells. This effect was
      particularly marked for drugs that act as inhibitors of protein synthesis. Since
      these anti-neoplastic drugs do not have anti-coagulant actions, these results
      provide evidence for the potential of targeting tumour fibrinogen as a new form
      of cancer chemotherapy.

PMID- 15458281
TI  - Immunogenicity and tolerability of a trivalent virosomal influenza vaccine in a
      cohort of HIV-infected children.
AB  - Twenty-three children infected with the human immunodeficiency virus (HIV) were
      vaccinated with a trivalent inactivated virosomal influenza vaccine. Serum
      haemagglutinin inhibition antibody titres were determined for the three viral
      strains at the time of vaccination and 1 month later. CD4 cell counts and HIV
      viral loads were measured to evaluate the effect of vaccination on HIV status.
      Adverse reactions were monitored during the first hour following vaccination by
      an investigator and then on a continuous basis by the parents. Seroconversion
      rates against the three viral strains A/H3N2, A/H1N1 and B were 73.9%, 56.5% and
      52.2%, respectively. Geometric mean antibody titres increased after 1 month
      compared with baseline values (A/H3N2: 70.9 versus 13.5; A/H1N1: 24.7 versus 5.8;
      B: 34.4 versus 9.1). No significant changes were observed in either HIV viral
      load or CD4 cell count following vaccination. Vaccination was well tolerated with
      only a few mild, transient symptoms.

PMID- 15458282
TI  - The effect of melatonin on plasma oxidant-antioxidant skeletal muscle reperfusion
      injury in rats.
AB  - We investigated the effects of melatonin administration on skeletal muscle
      ischaemia-reperfusion injury (IRI) by assessing plasma malondialdehyde (MDA),
      superoxide dismutase (SOD), total glutathione (GSSH), glutathione peroxidase
      (GPX) and myeloperoxidase (MPO) concentrations. Male Sprague-Dawley rats (n = 32)
      were randomized into four groups: group 1 served as time controls; group 2 were
      the test animals; group 3 received melatonin (30 mg/kg) intraperitoneally prior
      to the induction of ischaemia; and group 4 received melatonin (30 mg/kg)
      intraperitoneally prior to the reperfusion period. Administration of melatonin
      prior to reperfusion significantly decreased the elevated MDA concentration
      caused by IRI, and significantly elevated GSSH concentrations, which had been
      reduced by IRI. Ischaemia-reperfusion injury significantly increased activities
      of GPX, SOD and MPO, and melatonin administration reversed this effect. In
      conclusion, a pharmacological dose of melatonin showed significant protective
      effects against IRI by decreasing lipid peroxidation, MPO, SOD and GPX enzyme
      activities and regulating glutathione content.

PMID- 15458283
TI  - Promotion of fracture healing by vitamin E in rats.
AB  - We investigated the effects of the antioxidant alphae-tocopherol on early- and
      late-phase fracture healing in a rat model. Sixty male Sprague-Dawley rats were
      randomized into two groups. The right tibia of each rat was fractured manually
      under anaesthesia, and fracture sites fixed with intramedullary Kirschner wires.
      The alpha-tocopherol group received 20 mg/kg alpha-tocopherol intraperitoneally;
      the control group received intraperitoneal saline injections. Ten rats from each
      group were sacrificed on day 15, day 45 and day 60. In the alpha-tocopherol
      group, malondialdehyde concentrations, a measure of lipid peroxidation associated
      with oxygen free radicals, were significantly decreased on day 15 and day 45
      compared with the control group, but had regained the 15-day value on day 60. On
      histopathological and radiological assessment, fracture healing on day 60 was
      significantly more advanced in the alpha-tocopherol group. We conclude that alpha
      tocopherol has a positive effect on both early and late-phase fracture healing,
      and may be beneficial in clinical fracture

PMID- 15458284
TI  - The effects of bupivacaine and neostigmine on articular cartilage and synovium in
      the rabbit knee joint.
AB  - We investigated the effects of intra-articular injections of bupivacaine and
      neostigmine on articular cartilage and the synovial membrane of rabbit knee
      joints. Saline, bupivacaine or neostigmine were each administered intra
      articularly into 15 knee joints. Five joints per drug treatment were prepared for
      histopathological examination 24 h, 48 h and 10 days after injection. A
      pathologist examined the histological samples for inflammation of the articular
      cartilage, inflammatory cell infiltration, hypertrophy and hyperplasia of the
      synovial membrane, in a blinded manner. There no histopathological in the saline
      treated control joints. Joints treated with bupivacaine and neostigmine showed
      significantly more histopathological changes than control joints. Joints treated
      with neostigmine showed significantly more histopathological changes than those
      treated with bupivacaine, except for articular cartilage inflammation on day 10.
      We conclude that intra-articular bupivacaine and neostigmine cause
      histopathological changes in rabbit knee joints, with neostigmine having a
      greater effect than bupivacaine.

PMID- 15458285
TI  - Selective binding of sucralfate to endoscopic mucosal resection-induced gastric
      ulcer: evaluation of aluminium adherence.
AB  - We evaluated the effect of sucralfate in patients with early gastric cancer in
      endoscopic mucosal resection (EMR)-induced gastric ulcers, and in rats with
      acetic acid-induced ulcers, by measuring concentrations of aluminium adhering to
      mucosal lesions. Twenty-two patients who underwent EMR received sucralfate with
      or without ranitidine and were examined endoscopically after 1 week, 2 weeks and
      3 weeks. Gastric juice pH and concentration of aluminium in samples of ulcerated
      and normal mucosa were measured at various time-points. Good ulcer healing was
      observed in all patients. Significantly higher concentrations of aluminium were
      found in ulcerated tissue compared with normal mucosa. This selective binding of
      sucralfate was even found 12 h after drug administration and was confirmed in
      acetic acid-induced ulcers in 40 rats. Neutral rather than acid gastric juice was
      observed up to 12 h after the administration of sucralfate alone. These results
      suggest that sucralfate with or without ranitidine may contribute to the healing
      of EMR-induced ulcers by selectively binding to lesions.

PMID- 15458286
TI  - Antibacterial activity and clinical efficacy of sparfloxacin in Mycobacterium
      avium-intracellulare complex infection.
AB  - In Japan the incidence of atypical mycobacteriosis has steadily increased, with
      Mycobacterium avium-intracellulare complex (MAC) the most common infecting
      organism. A standard chemotherapy regimen for MAC infection has not been
      established because of significant resistance to anti-mycobacterial drugs.
      Sparfloxacin has good antimicrobial activity against several acid-fast bacteria
      and is expected to be an effective drug for treating mycobacteriosis. We examined
      the effects of adding sparfloxacin to anti-tuberculotic combination therapy in
      six patients with MAC pulmonary disease. Drug susceptibility was also assessed
      using the agar dilution method. The minimum inhibitory concentrations (MICs) for
      sparfloxacin, levofloxacin, isoniazid, rifampicin, streptomycin, ethambutol and
      clarithromycin was measured in clinical isolates from all patients; sparfloxacin
      showed the lowest MIC. Bacteriological and clinical improvements were observed in
      the four patients who completed the study. Dosing was discontinued in two
      patients because of pruritic skin eruptions. Sparfloxacin shows promise as an
      anti-mycobacterial agent for treating MAC pulmonary disease.

PMID- 15458287
TI  - Experience with teicoplanin in the treatment of neonatal staphylococcal sepsis.
AB  - We aimed to evaluate retrospectively the clinical and bacteriological efficacy
      and potential side-effects of teicoplanin treatment in neonates with proven
      staphylococcal infection. There were 37 episodes of staphylococcal septicaemia in
      neonates with a mean gestational age of 34.2 +/- 2.3 weeks; 26 were caused by
      coagulase-negative staphylococcal (CoNS) sepsis and 11 by Staphylococcus aureus
      sepsis. All episodes were treated with teicoplanin (intravenous loading dose 16
      mg/kg followed by a maintenance dose of 8 mg/kg daily). The methicillin
      resistance and antibiotic susceptibilities of both micro-organisms were
      evaluated. Bacterial eradication was achieved in 89.1% of cases and mortality was
      16.2%. The mean duration of treatment of the survivors was 11.6 +/- 2.3 days.
      There were no drug-related adverse events and the biochemical and haematological
      tests showed no clinically significant changes in relation to teicoplanin
      therapy. Our results suggest that teicoplanin is highly effective in neonatal
      staphylococcal sepsis.

PMID- 15458288
TI  - Chronotropic effect of the antithrombotic agent cilostazol in a patient with sick
      sinus syndrome and syncope.
AB  - In this case report we describe an 80-year-old man with sick sinus syndrome (SSS)
      who developed syncope attacks. The diagnosis of SSS was based on
      electrocardiographic evidence of markedly prolonged sinus arrests associated with
      syncope attacks while in hospital. The patient was given cilostazol, an
      antithrombotic agent that selectively inhibits cyclic nucleotide
      phosphodiesterase type 3, at a dose of 100 mg twice daily. The syncope attacks
      ceased, and an electrocardiogram obtained 1 week after the start of cilostazol
      administration showed no evidence of sinus arrest. The outcome of this case
      suggests that cilostazol may be useful in patients with syncope attacks due to
      SSS, although the long-term chronotropic effects of cilostazol need to be
      evaluated.

PMID- 15458289
TI  - Huge IgD plasmacytoma in the abdomen presenting coagulation necrosis.
AB  - A 65-year-old Japanese woman was diagnosed in 1996 with a pathological fracture
      of the left femur caused by immunoglobulin D-type myeloma (IgD myeloma). She
      responded well to combination chemotherapy followed by irradiation. The patient
      experienced renal failure and became dependent on haemodialysis. In 1999, large
      plasmacytomas developed in the abdomen and left humerus. The abdominal tumour
      appeared to induce gastroduodenal ulcers and jejunal obstruction. We initiated
      irradiation therapy without chemotherapy to prevent further growth of the
      plasmacytoma, although treatment-resistant gastroduodenal ulcers developed.
      Continued blood loss from the gastroduodenal ulcers resulted in a deterioration
      in the patient's health, which prevented successful haemodialysis. An autopsy
      showed that the plasmacytoma had undergone coagulation necrosis. We conclude that
      the use of combination chemotherapy with topical irradiation was an acceptable
      treatment measure against IgD plasmacytoma; irradiation without chemotherapy was
      the most likely cause of the coagulation necrosis seen in the plasmacytoma at
      autopsy.

PMID- 15458291
TI  - [Living in these times].

PMID- 15458290
TI  - Acute painful neuropathy restricted to the abdomen following rapid glycaemic
      control in type 2 diabetes.
AB  - A 46-year-old Japanese man with type 2 diabetes mellitus, whose only diabetic
      complication was simple retinopathy, developed acute painful neuropathy. This
      presented as paresthesia and hyperesthesia restricted to the abdomen. The
      patient's haemoglobin A(1c) had dropped from 12% to 7.5% within 5 months,
      following a rapid improvement in glycaemic control. On investigation, there were
      no indications of disease in the intraabdominal area. Nerve conduction studies
      were consistent with mild sensorimotor peripheral and autonomic neuropathy. The
      patient required medication (mexiletine, sulpiride and imipramine hydrochloride)
      to control the pain. Four months after presentation, the symptoms showed a
      dramatic improvement and the treatment for pain relief was discontinued without
      any recurrence of paresthesia or hyperesthesia in the patient's abdomen. This was
      a very unusual case of diabetic post-treatment painful neuropathy in which the
      prominent features were severe pain, paresthesia and hyperesthesia restricted to
      the abdomen.

PMID- 15458292
TI  - [The duration of work-time on the biological clock].

PMID- 15458293
TI  - [Image or information problem?].

PMID- 15458294
TI  - [Brightness and pain in childhood].

PMID- 15458295
TI  - ["The alternative must lean toward normality"].

PMID- 15458297
TI  - [Shining visions].

PMID- 15458296
TI  - [Two strong points and eight surrenders].

PMID- 15458298
TI  - ["Blind obedience disturbs me"].

PMID- 15458299
TI  - [Violence in social interaction].

PMID- 15458301
TI  - [Health: night work and twelve hour shifts].

PMID- 15458300
TI  - [The need for clarity].

PMID- 15458302
TI  - [Visibility: concerted actions].

PMID- 15458303
TI  - [Mission: protect children].

PMID- 15458304
TI  - [Preventing tension and conflict by means of humor].

PMID- 15458305
TI  - ["My last wishes..."--the time for discovery].

PMID- 15458307
TI  - [The identity of the patient is on the way to getting lost"].

PMID- 15458306
TI  - ["What sin have I committed?"].

PMID- 15458308
TI  - [Questions of ].

PMID- 15458309
TI  - [Child protection, the time and the place].

PMID- 15458310
TI  - [Domestic violence].

PMID- 15458311
TI  - Role of arginine in protein refolding, solubilization, and purification.
AB  - Recombinant proteins are often expressed in the form of insoluble inclusion
      bodies in bacteria. To facilitate refolding of recombinant proteins obtained from
      inclusion bodies, 0.1 to 1 M arginine is customarily included in solvents used
      for refolding the proteins by dialysis or dilution. In addition, arginine at
      higher concentrations, e.g., 0.5-2 M, can be used to extract active, folded
      proteins from insoluble pellets obtained after lysing Escherichia coli cells.
      Moreover, arginine increases the yield of proteins secreted to the periplasm,
      enhances elution of antibodies from Protein-A columns, and stabilizes proteins
      during storage. All these arginine effects are apparently due to suppression of
      protein aggregation. Little is known, however, about the mechanism. Various
      effects of solvent additives on proteins have been attributed to their
      preferential interaction with the protein, effects on surface tension, or effects
      on amino acid solubility. The suppression of protein aggregation by arginine
      cannot be readily explained by either surface tension effects or preferential
      interactions. In this review we show that interactions between the guanidinium
      group of arginine and tryptophan side chains may be responsible for suppression
      of protein aggregation by arginine.

PMID- 15458312
TI  - DNA microarrays: experimental issues, data analysis, and application to bacterial
      systems.
AB  - DNA microarrays are currently used to study the transcriptional response of many
      organisms to genetic and environmental perturbations. Although there is much room
      for improvement of this technology, its potential has been clearly demonstrated
      in the past 5 years. The general consensus is that the bottleneck is now located
      in the processing and analysis of transcriptome data and its use for purposes
      other than the quantification of changes in gene expression levels. In this
      article we discuss technological aspects of DNA microarrays, statistical and
      biological issues pertinent to the design of microarray experiments, and
      statistical tools for microarray data analysis. A review on applications of DNA
      microarrays in the study of bacterial systems is presented. Special attention is
      given to studies in the following areas: (1) bacterial response to environmental
      changes; (2) gene identification, genome organization, and transcriptional
      regulation; and (3) genetic and metabolic engineering. Soon, the use of DNA
      microarray technologies in conjunction with other genome/system-wide analyses
      (e.g., proteomics, metabolomics, fluxomics, phenomics, etc.) will provide a
      better assessment of genotype-phenotype relationships in bacteria, which serve as
      a basis for understanding similar processes in more complex organisms.

PMID- 15458313
TI  - Modeling rhl quorum-sensing regulation on rhamnolipid production by Pseudomonas
      aeruginosa.
AB  - The effect of autoinducer PAI2 on rhamnolipid (RL) production by Pseudomonas
      aeruginosa was evaluated using an rhlI null mutant of PAO1 added with PAI2 at
      various concentrations. A model has also been developed to describe the
      production kinetics regulated by the rhl quorum-sensing system in three steps:
      First, PAI2 combines with RhlR protein. Second, the activated complex RhlR:PAI2
      triggers the transcription (and expression) of the rhlAB operon that encodes for
      rhamnosyltransferase. Finally, the enzyme catalyzes the RL synthesis. The model
      describes fairly well the experimental results/profiles from three different
      studies (this and two others reported in the literature). The overall picture
      predicted by the model is as follows: The induced enzyme synthesis proceeds at
      the highest rate following PAI2 addition. The rate decreases with time as the
      autoinducer is degraded. The enzyme concentration nonetheless continues to
      increase until reaching the plateau at the exhaustion of autoinducer. Higher
      added PAI2 concentrations thus give not only higher initial enzyme synthesis
      rates but also longer induced synthesis. As the enzyme concentration increases
      with time, the RL production rate also increases, resulting in an accelerated
      rise in RL concentrations initially. The increase in RL concentrations becomes
      linear at the exhaustion of PAI2. The best-fit model parameters obtained also
      provided important insights. To complex half of the intracellular RhlR proteins
      would require 1.61 microM PAI2, about half of the PAI2 concentration obtained in
      the stationary-phase culture of wild-type PAO1. On the other hand, to activate
      the rhamnosyltransferase synthesis at half of its maximum rate would require the
      binding of 39% of RhlR with PAI2. The maximum RL production rate of the culture
      was found to be 0.042 g/L.h, and the fully induced culture would require at least
      1.61 h to synthesize the enzyme to the necessary level for producing RL at half
      of the maximum rate.

PMID- 15458314
TI  - Molecular cloning of polyhydroxyalkanoate synthesis operon from Aeromonas
      hydrophila and its expression in Escherichia coli.
AB  - The polyhydroxyalkanoate synthesis operon was cloned from Aeromonas hydrophila
      CGMCC 0911. Heterogeneous expression of the cloned polyhydroxyalkanoate synthesis
      operon in Escherichia coli resulted in accumulation of poly(3-hydroxybutyrate-co
      3-hydroxyhexanoate) consisting of 13.9 mol % 3-hydroxyhexanoate up to 29.2 wt %
      of cell dry weight when grown in lauric acid. The cell dry weight of recombinant
      E. coli harboring the polyhydroxyalkanoate synthesis operon was improved to 1.7 g
      L (-1), which was much higher than that of 0.3 g L (-1) of the wild type E. coli.
      Coexpression of acyl-CoA dehydrogenase gene (yafH) from E. coli and Vitreoscilla
      hemoglobin gene (vgb) from Vitreoscilla together with the whole A. hydrophila
      CGMCC 0911 polyhydroxyalkanoate synthesis operon facilitated cell growth and
      polyhydroxyalkanoate accumulation in E. coli. When yafH was coexpressed together
      with the polyhydroxyalkanoate synthesis operon, the poly(3-hydroxybutyrate-co-3
      hydroxyhexanoate) content was increased from 29.2 to 52.1 wt %, and the cell dry
      weight was also increased slightly from 1.70 to 1.86 g L (-1). Coexpression of
      vgb gene could further enhance the cell dry weight to 2.0 g L(-1) and the
      polyhydroxyalkanoate content to 60.7 wt %.

PMID- 15458315
TI  - Mathematical model of human growth hormone (hGH)-stimulated cell proliferation
      explains the efficacy of hGH variants as receptor agonists or antagonists.
AB  - Human growth hormone (hGH) is a therapeutically important endocrine factor that
      signals various cell types. Structurally and functionally, the interactions of
      hGH with its receptor have been resolved in fine detail, such that hGH and hGH
      receptor variants can be practically engineered by either random or rational
      approaches to achieve significant changes in the free energies of binding. A
      somewhat unique feature of hGH action is its homodimerization of two hGH
      receptors, which is required for intracellular signaling and stimulation of cell
      proliferation, yet the potencies of hGH mutants in cell-based assays rarely
      correlate with their overall receptor-binding avidities. Here, a mathematical
      model of hGH-stimulated cell signaling is posed, accounting not only for binding
      interactions at the cell surface but induction of receptor endocytosis and
      downregulation as well. Receptor internalization affects ligand potency by
      imposing a limit on the lifetime of an active receptor complex, irrespective of
      ligand-receptor binding properties. The model thus explains, in quantitative
      terms, the numerous published observations regarding hGH receptor agonism and
      antagonism and challenges the interpretations of previous studies that have not
      considered receptor trafficking as a central regulatory mechanism in hGH
      signaling.

PMID- 15458316
TI  - Screening of cyanobacterial species for calcification.
AB  - Species of cyanobacteria in the genera Synechococcus and Synechocystis are known
      to be the catalysts of a phenomenon called "whitings", which is the formation and
      precipitation of fine-grained CaCO3 particles. Whitings occur when the
      cyanobacteria fix atmospheric CO2 through the formation of CaCO3 on their cell
      surfaces, which leads to precipitation to the ocean floor and subsequent
      entombment in mud. Whitings represent one potential mechanism for CO2
      sequestration. Research was performed to determine the ability of various strains
      of Synechocystis and Synechococcus to calcify when grown in microcosms amended
      with 2.5 mM HCO(3-) and 3.4 mM Ca2+. Results indicated that although all strains
      tested have the ability to calcify, only two Synechococcus species, strains PCC
      8806 and PCC 8807, were able to calcify to the extent that a CaCO3 precipitate
      was formed. Enumeration of the cyanobacterial cultures during testing indicated
      that cell density did not appear to have a direct effect on calcification.
      Factors that had the greatest effect on calcification were CO2 removal and
      subsequent generation of alkaline pH. Whereas cell density was similar for all
      strains tested, differences in maximum pH were demonstrated. As CO2 was removed,
      growth medium pH increased and soluble Ca2+ was removed from solution. The
      largest increases in growth medium pH occurred when CO2 levels dropped below 400
      ppmv. Research presented demonstrates that, under the conditions tested, many
      species of cyanobacteria in the genera Synechocystis and Synechococcus are able
      to calcify but only two species of Synechococcus were able to calcify to an
      extent that led to the precipitation of calcium carbonate.

PMID- 15458317
TI  - Improvement of the thermoregulated T7 expression system by using the heat
      sensitive lacI.
AB  - The thermoregulated T7 expression system was previously reported to be an
      effective way to produce massive amounts of recombinant proteins (Chao, Y. P.;
      Law, W. S.; Chen, P. T.; Hung, W. B. High production of heterologous proteins in
      Escherichia coli using the thermo-regulated T7 expression system. Appl.
      Microbiol. Biotechnol. 2002b, 58, 446-453). To ensure its practical
      applicability, the system was improved for stringency with the construction of
      the T7lac-promoter-containing plasmid associated with the thermolabile lacI gene
      (lacIts). Owing to the recessive feature of lacIts, the wild-type lacI was
      removed from the genome of the cell. Moreover, the cell was engineered to carry
      the chromosomal copy of the T7 gene 1 subject to the regulation of lambdaPL and
      lambdaPR promoters. To characterize the system, the lacZ gene was fused to the
      T7lac promoter, and subsequent experiments showed that various amounts of LacZ
      could be synthesized in the plasmid-bearing cell in response to heat. Among the
      producers, the cell with the plasmid containing lacIts (substitution of Gly265
      with Asp in lacI) was able to produce the maximal LacZ, the production accounting
      for an amplification of more than 200-fold over the uninduced level. A further
      demonstration was carried out to illustrate the practical usefulness of the
      developed system by producing carbamoylase on a 4000 L scale. Cultured to reach
      high cell density, the carbamolyase-producing cell was shown to retain plasmids
      with 95% stability and to be capable of producing soluble protein equal to 13% of
      the total cell proteins. Overall, it illustrates the remarkable features of the
      developed system with tightness, high expression level, thermal inducibility, and
      high stability.

PMID- 15458318
TI  - Coexpression of Vitreoscilla hemoglobin reduces the toxic effect of expression of
      D-amino acid oxidase in E. coli.
AB  - Expression of the gene (daao) encoding D-amino acid oxidase (DAAO) in Escherichia
      coli typically results in a marked decrease of cell viability, and it has
      generally been assumed that the consumption of intracellular D-alanine by DAAO is
      responsible for this effect. Vitreoscilla hemoglobin (VHb) gene (vgb) was
      coexpressed with Rhodosporidium toruloides D-amino acid oxidase in E. coli
      BL21(DE3) and BL21(DE3)pLysS, expression hosts differing in the stringency of
      suppressing basal transcription. Not only was the toxic effect of DAAO on cell
      growth relieved but also the pronounced cell lysis of BL21(DE3)pLysS caused by
      the expression of DAAO was prevented by coexpressing VHb with DAAO. As a result
      of the higher cell density achieved, DAAO activity about 1.5-fold higher than
      that of DAAO-expressing control strains could be obtained by DAAO/VHb
      coexpressing strains. The relieving effect of VHb on DAAO toxicity resulted from
      its oxygen-binding ability. The low availability of free intracellular oxygen
      reduced DAAO activity and consequently its toxicity.

PMID- 15458319
TI  - Bacterial cellulose production by fed-batch fermentation in molasses medium.
AB  - Batch and fed-batch fermentations for bacterial cellulose (BC) production using
      molasses as a carbon source by Acetobacter xylinum BPR2001 were carried out in a
      jar fermentor. For improvement of BC production, molasses was subjected to H2SO4
      heat treatment. The maximum BC concentration by this treated molasses increased
      76%, and the specific growth rate increased 2-fold compared with that by
      untreated molasses. In batch fermentation, when the initial sugar concentrations
      of H2SO4-heat-treated molasses were varied from 20 to 70 g/L, the highest value
      of maximum BC concentration of 5.3 g/L was observed at 20 g/L. BC production in
      intermittent fed-batch (IFB) fermentation was conducted referring to the data in
      batch fermentation, and the highest BC production of 7.82 g/L was obtained when
      0.2 L of molasses medium was added five times. When continuous fed-batch (CFB)
      fermentations were conducted, maximum BC concentration was obtained with a
      feeding rate of 6.3 g-sugar/h, which was derived from the optimal IFB experiment.

PMID- 15458320
TI  - Air-filled porosity and permeability relationships during solid-state
      fermentation.
AB  - An experimental apparatus was constructed to measure the structural parameters of
      organic porous media, i.,e. mechanical strength, air-filled porosity, air
      permeability, and the Ergun particle size. These parameters are critical to the
      engineering of aerobic bioconversion systems and were measured for a straw-
      manure mixture before and after 13 days of in-vessel composting. Porosity was
      measured using air pycnometry at four (day 0) and five (day 13) moisture levels,
      with each moisture level tested at a range of different densities. Tested wet
      bulk densities varied with moisture level, but dry bulk densities generally
      ranged from 100 to 200 kg m(-3). At each moisture/density combination, pressure
      drop was measured at airflow rates ranging from 0.001 to 0.05 m sec(-1),
      representing the range of airflow rates found in both intensive and extensive
      composting. Measured air-filled porosities were accurately predicted from
      measurements of bulk density, moisture, and organic matter content. Reductions in
      air-filled porosity at increasing moisture content were accompanied by an
      increase in permeability, apparently due to aggregations of fines. This
      aggregation was quantified by calculating an effective particle size from the
      Ergun permeability relationship, which increased from 0.0002 m at 50% moisture to
      0.0021 m at 79% moisture. The range of airflow velocities reported in composting
      systems requires consideration of the second-order drag force term, particularly
      at velocities approaching 0.05 m s(-1) for the higher moisture treatments tested.
      Calculated permeabilities for the matrix ranged from 10(-10) to 10(-7) m2,
      varying with both air-filled porosity and moisture. Mechanical strength
      characterization provided a means to predict the effects of compaction on air
      filled porosity and permeability of porous media beds. The results of this
      investigation extend porous media theory to the organic matrices common in solid
      state fermentations and help build a framework for quantitative and mechanistic
      engineering design.

PMID- 15458321
TI  - Thermophilic (55-65 degrees C) and extreme thermophilic (70-80 degrees C) sulfate
      reduction in methanol and formate-fed UASB reactors.
AB  - The feasibility of thermophilic (55-65 degrees C) and extreme thermophilic (70-80
      degrees C) sulfate-reducing processes was investigated in three lab-scale upflow
      anaerobic sludge bed (UASB) reactors fed with either methanol or formate as the
      sole substrates and inoculated with mesophilic granular sludge previously not
      exposed to high temperatures. Full methanol and formate degradation at
      temperatures up to, respectively, 70 and 75 degrees C, were achieved when
      operating UASB reactors fed with sulfate rich (COD/SO4(2-)=0.5) synthetic
      wastewater. Methane-producing archaea (MPA) outcompeted sulfate-reducing bacteria
      (SRB) in the formate-fed UASB reactor at all temperatures tested (65-75 degrees
      C). In contrast, SRB outcompeted MPA in methanol-fed UASB reactors at
      temperatures equal to or exceeding 65 degrees C, whereas strong competition
      between SRB and MPA was observed in these reactors at 55 degrees C. A short-term
      (5 days) temperature increase from 55 to 65 degrees C was an effective strategy
      to suppress methanogenesis in methanol-fed sulfidogenic UASB reactors operated at
      55 degrees C. Methanol was found to be a suitable electron donor for sulfate
      reducing processes at a maximal temperature of 70 degrees C, with sulfide as the
      sole mineralization product of methanol degradation at that temperature.

PMID- 15458322
TI  - Production of low-lactose milk by means of nonisothermal bioreactors.
AB  - The effect of the immobilization time on the activity of immobilized beta
      galactosidase from K. lactis was investigated. Six biocatalytic membranes,
      different only for the time of the enzyme immobilization, were obtained by using
      nylon membranes grafted with glycidyl methacrylate (GMA) and activated by
      hexamethylenediamine (HMDA) and glutaraldehyde (Glu), used as spacer and coupling
      agent, respectively. Comparison between the isothermal and nonisothermal yield of
      these biocatalytic membranes was carried out in the process of lactose hydrolysis
      in milk. All of the results, reported as a function of the immobilization time,
      have evidenced the influence of our variable parameter on the activity of the
      catalytic membranes. The membrane giving highest yield under isothermal and
      nonisothermal conditions was that obtained with 2 h of immobilization time. The
      industrial application of these membranes has been discussed in terms of
      percentage reduction of the production times.

PMID- 15458323
TI  - Production of a secreted glycoprotein from an inducible promoter system in a
      perfusion bioreactor.
AB  - The primary advantage of an inducible promoter expression system is that
      production of the recombinant protein can be biochemically controlled, allowing
      for the separation of unique growth and production phases of the culture. During
      the growth phase, the culture is rapidly grown to high cell density prior to
      induction without the extra metabolic burden of exogenous protein production,
      thus minimizing the nonproductive period of the culture. Induction of the culture
      at high cell density ensures that the volumetric production will be maximized. In
      this work, we have demonstrated the feasibility of overexpressing a reporter
      glycoprotein from the inducible MMTV promoter in recombinant Chinese hamster
      ovary (CHO) cells cultured in a high cell density perfusion bioreactor system.
      Retention of suspension-adapted CHO cells was achieved by inclined sedimentation.
      To maximize volumetric production of the culture, we have demonstrated that high
      cell density must be achieved prior to induction. This operating scheme resulted
      in a 10-fold increase in volumetric titer over the low density induction culture,
      corresponding directly to a 10-fold increase in viable cell density during the
      highly productive period of the culture. The amount of glycoprotein produced in
      this high cell density induction culture during 26 days was 84-fold greater than
      that produced in a week long batch bioreactor. Long-term perfusion cultures of
      the recombinant cell line showed a production instability, a phenomenon that is
      currently being investigated.

PMID- 15458324
TI  - Hyperproduction of cordycepin by two-stage dissolved oxygen control in submerged
      cultivation of medicinal mushroom Cordyceps militaris in bioreactors.
AB  - Effect of oxygen supply on cordycepin production was investigated in submerged
      cultivation of Cordyceps militaris, a famous traditional Chinese medicinal
      mushroom, in a 5-L turbine-agitated bioreactor (TAB). Initial volumetric oxygen
      transfer coefficient (kLa) within the range of 11.5-113.8 h(-1) had significant
      influence on cordycepin production. The highest cordycepin concentration of 167.5
      mg/L was obtained at an initial kLa value of 54.5 h(-1), where a moderate
      dissolved oxygen (DO) pattern was observed throughout cultivation. The possible
      correlation between cordycepin production and DO level was explored by DO control
      experiments, and the results showed that DO within the range of 10-80% of air
      saturation greatly affected the cultivation process. To obtain a high specific
      cordycepin formation rate (rho) throughout cultivation, a two-stage DO control
      strategy was developed based on the analysis of the relationship of rho and DO.
      That is, DO was controlled at 60% from the beginning of cultivation and then
      shifted to a lower control level of 30% when rho started to decrease. As a
      result, a high cordycepin production of 201.1 mg/L and a high productivity of
      15.5 mg/(L.d) were achieved, which was enhanced by about 15% and 30% compared to
      the highest titers obtained in conventional DO control experiments, respectively.
      The proposed DO control strategy was also applied to a recently developed 5-L
      centrifugal impeller bioreactor (CIB) with cordycepin production and productivity
      titers of 188.3 mg/L and 14.5 mg/(L.d). Furthermore, the scale-up of the two
      stage DO control process from 5-L CIB to 30-L CIB was successfully demonstrated.
      The work is useful for the efficient large-scale production of bioactive
      metabolites by mushroom cultures.

PMID- 15458325
TI  - Immobilization of dextransucrase from Leuconostoc mesenteroides NRRL B-512F on
      Eupergit C supports.
AB  - Dextransucrase from Leuconostoc mesenteroides B-512F was immobilized on epoxy
      activated acrylic polymers with different textural properties (Eupergit C and
      Eupergit C 250L). Prior to immobilization, dextransucrase was treated with
      dextranase to remove the dextran layer covering the enzyme surface, thus
      increasing the accessibility of its reactive groups to the epoxide centers of the
      support. Elimination of 99% of the initial carbohydrate content was determined by
      the anthrone method. To prevent enzyme inactivation, the immobilization was
      carried out at pH 5.4, at which the coupling to the support took place through
      the carboxylic groups of the enzyme. The effects of the amount (mg) of
      dextransucrase added per gram of support (from 0.2:1 to 30:1), temperature and
      contact time were studied. Maximum activity recovery of 22% was achieved using
      Eupergit C 250L. Using this macroporous support, the maximum specific activity
      (710 U/g biocatalyst) was significantly higher than that obtained with the less
      porous Eupergit C (226 U/g biocatalyst). The dextransucrase immobilized on
      Eupergit C 250L showed similar optimal temperature (30 degrees C) and pH (5-6)
      compared with the native enzyme. In contrast, a notable stabilization effect at
      30 degrees C was observed as a consequence of immobilization. After a fast
      partial inactivation, the dextransucrase immobilized on Eupergit C 250L
      maintained more than 40% of the initial activity over the following 2 days. The
      features of this immobilized system are very attractive for its application in
      batch and fixed-bed bioreactors.

PMID- 15458326
TI  - Process considerations and economic evaluation of two-step steam pretreatment for
      production of fuel ethanol from softwood.
AB  - To increase the overall ethanol yield from softwood, the steam pretreatment stage
      can be carried out in two steps. The two-step pretreatment process was evaluated
      from a techno-economic standpoint and compared with the one-step pretreatment
      process. The production plants considered were designed to utilize spruce as raw
      material and have a capacity of 200,000 tons/year. The two-step process resulted
      in a higher ethanol yield and a lower requirement for enzymes. However, the two
      step process is more capital-intensive and has a higher energy requirement. The
      estimated ethanol production cost was the same, 4.13 SEK/L (55.1 cent /L) for
      both alternatives. For the two-step process different energy-saving options were
      considered, such as a higher concentration of water-insoluble solids in the
      filter cake before the second step, and the possibility of excluding the pressure
      reduction between the steps. The most optimistic configuration, with 50% water
      insoluble solids in the filter cake in the feed to the second pretreatment step,
      no pressure reduction between the pretreatment steps, and 77% overall ethanol
      yield (0.25 kg EtOH/kg dry wood), resulted in a production cost of 3.90 SEK/L
      (52.0 cent /L). This shows the potential for the two-step pretreatment process,
      which, however, remains to be verified in pilot trials.

PMID- 15458327
TI  - Polygalacturonic acid/endo-polygalacturonase system: a kinetic study in batch
      reactors.
AB  - The enzymatic depolymerization of the pectic substance polygalacturonic acid
      (PGA) is studied in batch reactor. The number-average molecular weight of native
      substrate is estimated, using a simple and quick technique, to be approximately
      11.1 kDa, the polymeric chains consisting on average of 63 galacturonic acid
      units. The effect of enzyme concentration was studied varying biocatalyst loading
      from 6 to 242 mg/L. The experiments were repeated at substrate concentrations
      ranging from 0.5 to 5 g/L. Data obtained at both short reaction time (20 min) and
      prolonged enzyme action (up to 350 min) are correlated using different kinetic
      equations, and the parameter values are discussed.

PMID- 15458328
TI  - Bioprocess equipment: characterization of energy dissipation rate and its
      potential to damage cells.
AB  - A study was conducted in which analytical, computational, and experimental
      measurements combined with analysis were made to characterize the local energy
      dissipation rate in a variety of conditions, vessels, and geometries that animal
      cells would encounter in typical bioprocessing situations. With no gas-liquid
      interfaces present, as expected, the local energy dissipation rate is typically
      orders of magnitude lower than what has been experimentally demonstrated to
      catastrophically damage typically used, suspended animal cells. However, local
      energy dissipation rates shown to remove animal cells from microcarriers are
      achievable under some normal operating conditions and geometries. Whether local
      energy dissipation rates created under typical operating conditions can have
      nonlethal effects is still an open question and currently under investigation.
      Whether the sensitivity of other, nontypical, suspended animal cells such as
      cells obtained directly from tissue (primary cells) and clusters of cells, such
      as islets, are more sensitive than the typically used cells is also still under
      investigation.

PMID- 15458329
TI  - Kinetics of Gibberella fujikuroi growth and gibberellic acid production by solid
      state fermentation in a packed-bed column bioreactor.
AB  - In this work the growth of Gibberella fujikuroi and gibberellic acid (GA3)
      production were studied using coffee husk and cassava bagasse as substrates in a
      packed-bed column bioreactor connected to a gas chromatograph for exit gas
      analysis. With the respirometric data, a logarithmic correlation between
      accumulated CO2 and biomass production was determined, and the kinetics of the
      fungal growth was compared for estimated and experimental data. The solid medium
      consisted of coffee husk (pretreated with alkali solution), mixed with cassava
      bagasse (7:3 dry weight basis), with a substrate initial pH of 5.2 and moisture
      of 77%. Cultivation was carried out in glass columns, which were packed with
      preinoculated substrate and with forced aeration of 0.24 L of air/[h (g of
      substrate)] for the first 3 days, and 0.72 L of air/[h (g of substrate)] for the
      remaining period. The maximum specific growth rate (microm) obtained was 0.052 h(
      1) (between 24 and 48 h of fermentation). A production of 0.925 g of GA3/kg of
      substrate was achieved after 6 days of fermentation.

PMID- 15458330
TI  - Simulated weightlessness in the design and exploitation of a NMR-compatible
      bioreactor.
AB  - Mammalian cells cultured in simulated weightlessness take advantage of a
      favorable environment, experiencing low shear stress and reduced turbulence. NMR
      spectroscopy allows the on-line noninvasive monitoring of cell growth and
      metabolism. With this in mind, we developed a novel bioreactor that fits into a
      NMR instrument and in which the simulated weightlessness conditions are obtained
      by a suitable medium and a flow-lift suspension. In detail, the gravitational
      vector acting on cells is counterbalanced by the hydrodynamic thrusts created by
      a bottom-up spiral flow of a fluid having increased density. We validate its
      efficiency (a) by calculating the main physical parameters as relative velocity,
      shear stress, and oxygen transport, and (b) by comparing the experimental results
      of growing a cell culture in the proposed bioreactor with those obtained using an
      established simulated weightlessness system (rotating wall vessel, NASA). As a
      test study we focused on the proliferation of human umbilical vein endothelial
      cells (HUVEC) in terms of cell viability and organization of their cytoskeleton.

PMID- 15458331
TI  - Modeling of immobilized cell columns for bioconversion and wastewater treatment.
AB  - Immobilized cells are widely used in bioconversions to produce biological
      products as well as in wastewater treatment such as solvent removal from
      wastewater streams. In this work, a rate model is proposed to simulate this kind
      of process in an axial-flow fixed-bed column packed with porous particles
      containing immobilized cells. The transient model considered various mass
      transfer mechanisms including axial dispersion, interfacial film mass transfer,
      and intraparticle diffusion. Cell death in the immobilized cell system was also
      considered. Effects of various parameters such as kinetic constants and mass
      transfer parameters were studied. Operational situations such as feed fluctuation
      flow rate increase and two columns in series were also investigated. The model
      can be used to study the behavior and characteristics of immobilized cell columns
      in order to perform scale-up predictions of effluent profiles and for the purpose
      of process optimization.

PMID- 15458332
TI  - Kinetics of the alkaline phosphatase catalyzed hydrolysis of disodium p
      nitrophenyl phosphate: effects of carbohydrate additives, low temperature, and
      freezing.
AB  - The kinetics of the alkaline phosphatase catalyzed hydrolysis of disodium p
      nitrphenyl phosphate was studied at 25 degrees C in the presence of the
      carbohydrates sucrose, fructose, lactose, maltodextrin (DE = 13-17),
      carboxymethylcellulose (CMC), and CMC-lactose (in 1:1 proportion) at different
      concentrations and in the presence of sucrose at two different concentrations in
      a temperature range between 25 and -10 degrees C in subcooled and frozen systems.
      The objective was to determine whether the reaction is diffusion-controlled, to
      gain an insight about the factors that determine the diffusion of the reaction
      species, to understand the mechanism through which the different carbohydrate
      additives affect the kinetics of the reaction, and to determine the effect of low
      temperature and freezing on the structural conformation of the enzyme. It was
      found that the alkaline phosphatase catalyzed hydrolysis of DNPP under the
      condition studied is at least partially diffusion-controlled. The results also
      indicate that the diffusion is not controlled by the macroviscosity of the
      reaction media. The concentration and type of the molecules that constitute the
      background matrix seem to be the main factors governing the reaction. The results
      indicate that the different carbohydrates affect the kinetics of the reaction
      through the excluded volume effect of molecular crowding and decreased substrate
      and product diffusion rate and not through nonspecific solute effects, which may
      cause protein denaturation and alteration in enzyme activity. Low temperature
      does not seem to affect the structural conformation of the enzyme in the
      temperature range studied, whereas freezing affected the catalytic properties of
      the enzyme perhaps through its effect on the structural conformation of the
      enzyme.

PMID- 15458333
TI  - Inexpensive and generic affinity purification of recombinant proteins using a
      family 2a CBM fusion tag.
AB  - The selective binding of the family 2a carbohydrate binding module (CBM2a) of
      xylanase 10A of the soil bacterium Cellulomonas fimi to a variety of cellulosic
      substrates is shown to provide a new, cost-effective affinity chromatography
      system for purification of recombinant protein. Genetic linkage of CBM2a to a
      target protein, in this case protein A from Staphylococcus aureus, results in a
      fusion protein that binds strongly to the particulate-cellulose resin Avicel
      PH101 and retains the biological activity of the fusion partner. Affinity
      purification of protein A-CBM2a from the supernatant of a recombinant E. coli
      JM101 culture results in a product purity of greater than 95% and a product
      concentration factor of 34 +/- 3. Measured column parameters are combined with
      one-dimensional equations governing continuity and intraparticle diffusion to
      predict product breakthrough curves with good accuracy over the range of
      realistic operating conditions. Peak spreading within the column is controlled by
      intraparticle diffusion for CBM2a and by a combination of film mass transfer and
      intraparticle diffusion for the larger protein A-CBM2a fusion protein.

PMID- 15458334
TI  - Evaluation of microbeads of calcium alginate as a fluidized bed medium for
      affinity chromatography of Aspergillus niger Pectinase.
AB  - Calcium alginate microbeads (212-425 microm) were prepared by spraying 2% (w/v)
      alginate solution into 1 M CaCl2 solution. The fluidization behavior of these
      beads was studied, and the bed expansion index and terminal velocity were found
      to be 4.3 and 1808 cm h(-1), respectively. Residence time distribution curves
      showed that the dispersion of the protein was much less with these microbeads
      than with conventionally prepared calcium alginate macrobeads when both kinds of
      beads were used for chromatography in a fluidized bed format. The fluidized bed
      of these beads was used for the purification of pectinase from a commercial
      preparation. The media performed well even with diluted feedstock; 90% activity
      recovery with 211-fold purification was observed.

PMID- 15458335
TI  - Mass transfer kinetics in the chromatography of insulin variants under nonlinear
      conditions.
AB  - Experimental data regarding the thermodynamics and kinetics of adsorption of
      lispro, an insulin variant, onto a YMC ODS-A column, from an aqueous solution of
      acetonitrile (31%) and TFA are reinterpreted, using a more complex model of the
      mass transfer kinetics. The adsorption behavior follows the Toth isotherm model,
      suggesting either a strongly heterogeneous surface or, rather, that when insulin
      molecules adsorb they contact the surface along different areas of the molecule.
      The lumped pore diffusion (POR) model of chromatography accounts well for the
      band profiles. The internal mass transfer resistances are higher than expected,
      which suggests that intraparticle diffusion is slower. Furthermore, the pore
      diffusion coefficient increases with decreasing sample size. That surface
      diffusion accounts for the mass transfer kinetics inside particles explains these
      results. Assuming that the gradient of the surface concentration is the driving
      force of surface diffusion, it is possible to account very well for the band
      profiles of samples of widely different sizes, using a single value of the
      surface diffusivity.

PMID- 15458336
TI  - A simple strategy for the purification of large thermophilic proteins
      overexpressed in mesophilic microorganisms: application to multimeric enzymes
      from Thermus sp. strain T2 expressed in Escherichia coli.
AB  - The heating of protein preparations of mesophilic organism (e.g., E. coli)
      produces the obliteration of all soluble multimeric proteins from this organism.
      In this way, if a multimeric enzyme from a thermophilic microorganism is
      expressed in these mesophilic hosts, the only large protein remaining soluble in
      the preparation after heating is the thermophilic enzyme. These large proteins
      may be then selectively adsorbed on lowly activated anionic exchangers, enabling
      their full purification in just these two simple steps. This strategy has been
      applied to the purification of an alpha-galactosidase and a beta-galactosidase
      from Thermus sp. strain T2, both expressed in E. coli, achieving the almost full
      purification of both enzymes in only these two simple steps. This very simple
      strategy seems to be of general applicability to the purification of any
      thermophilic multimeric enzyme expressed in a mesophilic host.

PMID- 15458337
TI  - Moderate temperatures affect Escherichia coli inactivation by high-pressure
      homogenization only through fluid viscosity.
AB  - The inactivation of suspensions of Escherichia coli MG1655 by high-pressure
      homogenization was studied over a wide range of pressures (100-300 MPa) and
      initial temperatures of the samples (5-50 degrees C). Bacterial inactivation was
      positively correlated with the applied pressure and with the initial temperature.
      When samples were adjusted to different concentrations of poly(ethylene glycol)
      to have the same viscosity at different temperatures below 45 degrees C and then
      homogenized at these temperatures, no difference in inactivation was observed.
      These observations strongly suggest, for the first time, that the influence of
      temperature on bacterial inactivation by high-pressure homogenization is only
      through its effect on fluid viscosity. At initial temperatures > or =45 degrees
      C, corresponding to an outlet sample temperature >65 degrees C, the level of
      inactivation was higher than what would be predicted on the basis of the reduced
      viscosity at these temperatures, suggesting that under these conditions heat
      starts to contribute to cellular inactivation in addition to the mechanical
      effects that are predominant at lower temperatures. Second-order polynomial
      models were proposed to describe the impact of a high-pressure homogenization
      treatment of E. coli MG1655 as a function of pressure and temperature or as a
      function of pressure and viscosity. The pressure-viscosity inactivation model
      provided a better quality of fit of the experimental data and furthermore is more
      comprehensive and versatile than the pressure-temperature model because in
      addition to viscosity it implicitly incorporates temperature as a variable.

PMID- 15458338
TI  - Downstream process synthesis for biochemical production of butanol, ethanol, and
      acetone from grains: generation of optimal and near-optimal flowsheets with
      conventional operating units.
AB  - Manufacturing butanol, ethanol, and acetone through grain fermentation has been
      attracting increasing research interest. In the production of these chemicals
      from fermentation, the cost of product recovery constitutes the major portion of
      the total production cost. Developing cost-effective flowsheets for the
      downstream processing is, therefore, crucial to enhancing the economic viability
      of this manufacturing method. The present work is concerned with the synthesis of
      such a process that minimizes the cost of the downstream processing. At the
      outset, a wide variety of processing equipment and unit operations, i.e.,
      operating units, is selected for possible inclusion in the process. Subsequently,
      the exactly defined superstructure with minimal complexity, termed maximal
      structure, is constructed from these operating units with the rigorous and highly
      efficient graph-theoretic method for process synthesis based on process graphs (P
      graphs). Finally, the optimal and near-optimal flowsheets in terms of cost are
      identified.

PMID- 15458339
TI  - Extracellular release of recombinant alpha-amylase from Escherichia coli using
      pulsed electric field.
AB  - It is difficult for Escherichia coli to secrete products such as recombinant
      enzymes, because the Gram-negative bacterium has a double membrane structure and
      so some of the products are accumulated in a periplasmic space. In this study, we
      demonstrated that recombinant alpha-amylase can be released from recombinant E.
      coli HB101/pHI301A during cultivation by applying a pulsed electric field (PEF).
      When a PEF (12 kV, 2 Hz) was applied for 30 min with an interval of 30 min from
      the point of OD660=0.7, the amount of released alpha-amylase was about 30% of the
      total amount of alpha-amylase produced in the cells. As a result of SDS-PAGE and
      activity staining analyses, it was confirmed that the released proteins were not
      all of the intracellular proteins, and the alpha-amylase, which was identical
      with intracellular alpha-amylase, was released by applied PEF cultivation. PEF
      treatment could be useful for easy release of periplasmic protein with
      selectivity.

PMID- 15458340
TI  - Physicochemical parameters involved in the interaction of Saccharomyces
      cerevisiae cells with ion-exchange adsorbents in expanded bed chromatography.
AB  - Expanded bed adsorption (EBA) is an interesting primary technology allowing the
      adsorption of target proteins from unclarified feedstock in order to combine
      separation, concentration, and purification steps. However, interactions between
      cells and adsorbent beads during the EBA process can strongly reduce the
      performance of the separation. So, to minimize these interactions, the mechanisms
      of cell adsorption on the support were investigated. Adsorption kinetics of the
      baker's yeast Saccharomyces cerevisiae on the anion exchanger Q Hyper Z were
      directly performed under real EBA operating conditions, in a lab-scale UpFront 10
      column. The yeast was marketed either as rod-shaped pellets (type I yeast) or as
      spherical pellets (type II yeast). For both types, a complete series of
      experiments for determining the adsorption profile versus time was performed,
      varying the superficial velocity or the pH. In parallel, the surface
      physicochemical properties of the cells (surface charge and electron-donor and
      electron-acceptor components) and of the support were determined. First of all,
      whatever the yeast types, the relation between cell adsorption and bed expansion
      has been highlighted, demonstrating the important role of hydrodynamic. However,
      for the type II yeast cells, adsorption increased dramatically, compared to the
      type I, even though it was shown that both types exhibited the same surface
      charge. In fact, there were strong differences in the Lewis acidic and basic
      components of the two yeasts. These differences explain the variable affinity
      toward the support, which was characterized by a strong electron-donor and a weak
      electron-acceptor component. These observed behaviors agreed with the colloidal
      theory. This work demonstrates that all kinds of interaction between the cells
      and the support (electrostatic, Lifshitz-van der Waals, acid/base) have to be
      taken into account together with hydrodynamic characteristics inside the bed.

PMID- 15458341
TI  - Effect of Cl- and H+ on the oxygen binding properties of glutaraldehyde
      polymerized bovine hemoglobin-based blood substitutes.
AB  - Bovine hemoglobin was cross-linked with glutaraldehyde, resulting in high oxygen
      affinity polymeric hemoglobin dispersions of varying molecular weight
      distributions. High oxygen affinity acellular oxygen carriers were designed in
      order to exhibit oxygen release profiles closer to that of human red blood cells
      (RBCs), without exhibiting the inherent increased vasoactivity that occurs with
      low oxygen affinity acellular oxygen carriers (1, 2). Oxygen dissociation curves
      were measured for polymerized hemoglobin dispersions at various pH values (7.0,
      7.4, and 8.0) and chloride ion concentrations. Unmodified hemoglobin showed an
      increase in oxygen affinity with increased chloride ion concentration and a
      decrease in oxygen affinity with increased pH, as was previously demonstrated in
      the literature (3). For glutaraldehyde-polymerized hemoglobin dispersions, the
      ability of the oxygen affinity to respond to changes in Bohr H+ and Cl-
      concentration was weakened. However, at acidic physiological pH (pH = 7), the
      Bohr effect was still present at high Cl- concentrations. Thus, the Bohr effect
      maintained some dependency on the Cl- concentration.

PMID- 15458342
TI  - Modified oligosaccharides as potential dental plaque control materials.
AB  - Metabolic acids produced by oral pathogens demineralize tooth surfaces, leading
      to dental caries. Glucosyltransferases are the key factor in this process. We
      synthesized various modified oligosaccharides and tested them for their
      inhibitory effects on glucosyltransferase activity. Oligosaccharides were
      produced using a mixed-culture fermentation of Lipomyces starkeyi and Leuconostoc
      mesenteroides and then further modified as iron- and sulfate-oligosaccharides.
      Iron- and sulfate-oligosaccharides reduced glucosyltransferase activity of
      Streptococci from 17% to 43% and prevented the formation of insoluble biomass on
      the surface of glass vials or stainless steel wires in the presence of sucrose.
      They also reduced the growth and acid productions of oral pathogens including S.
      mutans, S. sobrinus, Eikenella corrodens, Prevotella intermedia, and
      Actinobacillus actinomycetemcmitans.

PMID- 15458343
TI  - Enhanced glucose to fructose conversion in acetone with xylose isomerase
      stabilized by crystallization and cross-linking.
AB  - The effects of acetone and ethanol on glucose to fructose conversion catalyzed by
      soluble and cross-linked crystalline (CLXIC) xylose isomerase were studied.
      Relative to pure buffer solvent, the fructose production rate was more than
      doubled in 50% acetone. The same kind of increase in the isomerization rate was
      not seen with ethanol. Increase both in acetone and in ethanol concentration in
      the reaction solvent enhanced the production of fructose. At 50 degrees C in pure
      buffer solvent the reaction mixture contained 49% fructose in equilibrium and in
      90% acetone the fructose equilibrium content was 64%. Furthermore, CLXIC was
      relatively stable in the presence of high concentration of acetone: 70-80% of
      activity was left after incubation for 24 h at 50 degrees C in buffer solutions
      (pH 7.2) containing 10-90% acetone. In buffer containing 50% ethanol only 2% of
      the initial activity of CLXIC was retained after 24 h at 50 degrees C. Soluble
      xylose isomerase was considerably less stable than CLXIC in both acetone- and
      ethanol-containing solutions. These results show that the addition of acetone
      enhances the production of fructose from glucose by enhancing the reaction rate
      and shifting the equilibrium toward fructose. However, xylose isomerase must be
      in the form of cross-linked crystals for maximal activity and stability.

PMID- 15458344
TI  - Fluorescence lifetime spectroscopy of a pH-sensitive dye encapsulated in hydrogel
      beads.
AB  - A pH-sensing dye, carboxy seminaphthofluorescein-1 (C-SNAFL-1), was immobilized
      in poly(ethylene glycol) (PEG) microparticles via ester-amine reaction. Following
      photopolymerization, the hydrogel particles were then immersed in buffered pH
      solutions of varying pH with added polystyrene. Measurements of phase shift and
      amplitude attenuation of the generated and multiply scattered fluorescent light
      were attained as a function of modulation frequency of the incident excitation
      light. Upon regressing the measured data to the coupled optical diffusion
      equations, the average lifetimes of protonated and deprotonated forms of C-SNAFL
      1 were obtained and compared to the values acquired from conventional
      fluorescence lifetime spectroscopy in nonscattering media. The results
      demonstrate the ability to perform analyte sensing with fluorescence lifetime
      without the confounding effect of fluorophore loading or the use of a "reference"
      measurement within multiply scattering systems. When extended to the immobilized
      fluorophore-enzymatic systems, fluorescence lifetime spectroscopy with multiply
      scattered light may provide a new ultrasensitive approach for analyte or toxin
      screening.

PMID- 15458345
TI  - Bioremediation of organophosphorus pesticides by surface-expressed
      carboxylesterase from mosquito on Escherichia coli.
AB  - The insecticide resistance-associated esterase, carboxylesterase B1 (CaE B1),
      from mosquito was used to degrade the organophosphorus compounds. To eradicate
      the need for enzyme purification and minimize the resistance to mass transport of
      the substrate and product across the cell membranes, the CaE B1 was displayed on
      the cell surface of Escherichia coli fused to the C-terminus of the ice
      nucleation protein (INP). The presence of CaE B1 on the bacterial cell surface
      was verified by SDS-PAGE, Western blotting analysis, and immunofluorescence
      microscopy. More than 50% of active CaE B1 is exported across the membrane and
      anchored onto the cell surface as determined by proteinase accessibility and cell
      fractionation experiments. In contrast, only a 6% drop in activity for proteinase
      K-treated cells was detected from E.coli cells containing pET-B1. From the
      degradation experiment, more than 80% of the malathion was degraded by whole
      cells containing plasmid pUC-NC-B1. Constitutive expression of CaE B1 on the
      surface using INPNC resulted in no cell lysis, and the suspended cultures also
      exhibited good stability. Because of their high biodegradation activity and
      superior stability, these "live biocatalysts" are promising for detoxification of
      organophosphorus pesticides.

PMID- 15458346
TI  - A thermostable sugar-binding protein from the Archaeon Pyrococcus horikoshii as a
      probe for the development of a stable fluorescence biosensor for diabetic
      patients.
AB  - In this work is presented the first attempt to develop an innovative ultrastable
      protein-based biosensor for blood glucose detections. The gene of a putative
      thermostable sugar-binding protein has been cloned and expressed in E. coli. The
      recombinant protein has been purified to homogeneity by thermoprecipitation and
      affinity chromatography steps. The recombinant protein is a monomer with an
      apparent molecular weight of 55,000 as judged by gel filtration and sodium
      dodecyl sulfate polyacrylamide gel eletrophoresis. Circular dichroism experiments
      showed that the protein possesses a secondary structure content rich in alpha
      helices and beta-structures and that the protein is highly stable as investigated
      in the range of temperature between 20 and 95 degrees C. Fluorescence
      spectroscopy experiments demonstrated that the recombinant protein binds glucose
      with a dissociation constant of about 10 mM, a concentration of sugar very close
      to the concentration of glucose present in the human blood. A docking simulation
      on the modeled structure of the protein confirms its ability to bind glucose and
      proposes possible modifications to improve the affinity for glucose and/or its
      detection. The obtained results suggest the use of the protein as a probe for a
      stable glucose biosensor.

PMID- 15458347
TI  - Purification of a catalase from Thermus thermophilus via IMAC chromatography:
      effect of the support.
AB  - A hexameric Mn-catalase was purified from crude extracts of Thermus thermophilus
      using ammonium sulfate precipitation and ion metal-chelate affinity
      chromatography (IMAC). Eupergit 250 and Sepabeads FP-EP3 epoxy supports
      derivatized with iminodiacetic acid (IDA) and copper were used, at similar
      micromole/packed milliliter of support. Although Eupergit 250-IDA-Cu support
      adsorbed 80% of the total proteins in the extract, it exhibited a minimum
      affinity for the catalase. On the other hand, Sepabeads FP-EP3-IDA-Cu allowed the
      full adsorption of the catalase activity, which could be desorbed in fractions of
      different purity. This was attributed to a different geometrical congruence of
      the support surfaces with the enzyme surface, resulting in a different ability to
      form multipoint interactions with the proteins. Thus, by a cleanup step, followed
      by a negative chromatographic step using Eupergit 250-IDA-Cu2+ and by the
      adsorption of the catalase on Sepabeads-IDA-Cu2+ support, a pure enzyme fraction
      was obtained and its N-terminal end was sequenced.

PMID- 15458348
TI  - Chlorpromazine N-demethylation by hydroperoxidase activity of covalent
      immobilized lipoxygenase.
AB  - This work describes the application of the N-demethylase activity of immobilized
      soybean lipoxygenase to the oxidative degradation of xenobiotics. Previously (1)
      we have shown that immobilized lipoxygenase produces the oxidative degradation of
      CPZ in the presence of hydrogen peroxide. As a continuation of this work, here we
      studied the N-demethylation of CPZ by the hydroperoxidase activity of covalent
      immobilized soybean lipoxygenase. The obtained results clearly reveal that the
      immobilized system produces the N-demethylation of CPZ in the presence of
      hydrogen peroxide, maintaining a high level of activity in comparison with free
      enzyme. Additionally, the immobilized lipoxygenase shows stability higher than
      that of free enzyme, making feasible its use in a bioreactor operating in
      continuous or discontinuous mode. The results obtained in this work, together
      with those obtained previously by us for the oxidation of CPZ, suggest that
      hydroperoxidase activity of immobilized lipoxygenase may constitute a valuable
      tool for oxidative xenobiotics degradation or for application to synthetic
      processes in which a N-demethylation reaction is involved.

PMID- 15458349
TI  - Predicting dye biodegradation from redox potentials.
AB  - Two biological approaches for decolorization of azo sulfonated dyes have been
      compared: reductive decolorization with the ascomycete yeast Issatchenkia
      occidentalis and enzymatic oxidative decolorization with Trametes villosa laccase
      alone or in the presence of the mediator 1-hydroxybenzotriazole. The redox
      potential difference between the biological cofactor involved in the reductive
      activity of growing cells and the azo dye is a reliable indication for the
      decolorization ability of the biocatalyst. A linear relationship exists between
      the redox potential of the azo dyes and the decolorization efficiency of enzyme,
      enzyme/mediator, and yeast. The less positive the anodic peak of the dye, the
      more easily it is degraded oxidatively with laccase. The more positive the
      cathodic peak of the dye, the more rapidly the dye molecule is reduced with
      yeast.

PMID- 15458350
TI  - Correlation of denitrification-accepted fraction of electrons with NAD(P)H
      fluorescence for Pseudomonas aeruginosa performing simultaneous denitrification
      and respiration at extremely low dissolved oxygen conditions.
AB  - In cystic fibrosis airway infection, Pseudomonas aeruginosa forms a microaerobic
      biofilm and undergoes significant physiological changes. It is important to
      understand the bacterium's metabolism at microaerobic conditions. In this work,
      the culture properties and two indicators (the denitrification-accepted e-
      fraction and an NAD(P)H fluorescence fraction) for the culture's "fractional
      approach" to a fully anaerobic denitrifying state were examined in continuous
      cultures with practically zero DO but different aeration rates. With decreasing
      aeration, specific OUR decreased while specific NAR and NIR increased and kept
      Y(ATP/S) relatively constant. P. aeruginosa thus appeared to effectively
      compensate for energy generation at microaerobic conditions with denitrification.
      At the studied dilution rate of 0.06 h(-1), the maximum specific OUR was 2.8 mmol
      O2/g cells-h and the Monod constant for DO, in the presence of nitrate, was
      extremely low (<0.001 mg/L). The cell yield Y(X/S) increased significantly (from
      0.24 to 0.34) with increasing aeration, attributed to a roughly opposite trend of
      Y(ATP/X) (ATP generation required for cell growth). As for the denitrification
      accepted e- fraction and the fluorescence fraction, both decreased with
      increasing aeration as expected. The two fractions, however, were not directly
      proportional. The fluorescence fraction changed more rapidly than the e- fraction
      at very low aeration rates, whereas the opposite was true at higher aeration. The
      results demonstrated the feasibility of using online NAD(P)H fluorescence to
      monitor sensitive changes of cellular physiology and provided insights to the
      shift of e- -accepting mechanisms of P. aeruginosa under microaerobic conditions.

PMID- 15458351
TI  - Increasing the acetyl-CoA pool in the presence of overexpressed
      phosphoenolpyruvate carboxylase or pyruvate carboxylase enhances succinate
      production in Escherichia coli.
AB  - An in vivo strategy to apply the activation effect of acetyl-CoA on
      phosphoenolpyruvate carboxylase (PEPC) and pyruvate carboxylase (PYC) to increase
      succinate production in Escherichia coli was studied. This approach relies on the
      increased intracellular acetyl-CoA and CoA levels by overexpressing E. coli
      pantothenate kinase (PANK). The results showed that coexpression of PANK and
      PEPC, and PANK and PYC, did improve succinate production compared to the
      individual expression of PEPC and PYC, respectively. The intracellular acetyl-CoA
      and CoA levels were also measured, and each showed a significant increase when
      the PANK was overexpressed. Another effect observed was a decrease in lactate
      production. The least amount of lactate was produced when PANK and PEPC, and PANK
      and PYC, were coexpressed. This result showed increased competitiveness of the
      succinate pathway at the phosphoenolpyruvate and pyruvate nodes for the carbon
      flux, as a result reducing the carbon flux toward the lactate pathway. The study
      also demonstrates a feasible method for metabolic engineering to modulate enzyme
      activity in vivo through specific activators and inhibitors.

PMID- 15458352
TI  - Secret signatures inside genomic DNA.
AB  - A simple, practical method to watermark short trademarks or signatures into
      genomic DNA is introduced. Since the marking method is biologically innocuous, it
      can be applied to all commercialized bacteria to help establish brand names for
      the engineered strains and to resolve legal disputes regarding gene-related
      patents. The first such strain of Bacillus subtilis is engineered and is ready to
      be distributed.

PMID- 15458353
TI  - Phases dispersion and oxygen transfer in a simulated fermentation broth
      containing castor oil and proteins.
AB  - The sizes of air bubbles and castor oil drops were studied by image analysis as a
      function of the concentration of soluble protein (bovine serum albumin [BSA] and
      lipase, as model proteins) in a three-phase system using a simulated fermentation
      medium (aqueous salt solution, castor oil, and air). Small amounts of proteins
      (<0.02 g/L) caused an important decrease in oil drops and bubbles sizes, together
      with a pronounced decrease in surface tension. The extent and profiles of this
      decrease seem to be determined by the conformation of the protein at the
      interface. The kLa value increased considerably for increasing concentration (up
      to 0.02 g/L) of the two proteins but was very different (2-fold higher for the
      lipase) at the highest concentrations tested (0.5 g/L), a phenomenon that can be
      caused by the extent to which bubbles are trapped within oil drops.

PMID- 15458355
TI  - [Histopathological diagnosis of mycoses].
AB  - Infectious diseases emerge as a cause of pathology in our patients. Among the
      possible etiologies, mycoses have shown a considerable increase in the two last
      decades. In general, the clinical features of fungal diseases are not very
      distinctive. The morphology and the clinical aspects of the fungi serve as a
      protocol for their correct identification. Clinicians, microbiologists and
      pathologists are essential for the diagnosis. The pathologist using a simple and
      fast methodology can diagnose some types of mycosis, but they do not only
      identify the causal agent, but also the kind of injury that produces, the
      inflammatory response and the affected organ or organs. Moreover, they can
      classify the mycosis as superficial, cutaneous, subcutaneous, deep and systemic
      depending on the location. The present review paper describes study guidelines
      for the pathologist faced with a fungal infection and new technical advances that
      are established in pathology laboratories for a more precise identification of
      the mycoses.

PMID- 15458356
TI  - Is there a role for antibody testing in the diagnosis of invasive candidiasis?
AB  - During the last decades, the use of antibody tests for the diagnosis of invasive
      mycoses has declined as a consequence of the general belief that they are
      insensitive and non-specific. However, there is a clear evidence that antibodies
      can be detected in highly immunodeficient patients (such as bone marrow
      transplant recipients), and that those antibodies are useful for the diagnosis.
      Antibody tests are currently in use as diagnostic tools for some primary mycoses,
      such as the endemic mycoses, aspergilloma, allergic bronchopulmonary aspergilosis
      and sporothrichosis. For invasive candidiasis, diagnostic methods must
      differentiate Candida colonization of mucous membranes or superficial infection
      from tissue invasion by this microorganism. Substantial progress has been made in
      diagnosis of invasive candidiasis with the development of a variety of methods
      for the detection of antibodies and antigens. However, no single test has found
      widespread clinical use and there is a consensus that diagnosis based on a single
      specimen lacks sensitivity. It is necessary to test sequential samples taken
      while the patient is at greatest risk for developing invasive candidiasis to
      optimize the diagnosis. Results obtained from a panel of diagnostic tests in
      association with clinical aspects will likely be the most useful strategy for
      early diagnosis and therapy.

PMID- 15458357
TI  - [Molecular identification methods of yeasts of biotechnological interest].
AB  - Yeasts have numerous applications in modern and traditional biotechnology. They
      take place in production of food, unicellular protein and products with added
      value, and in the last decades they have been incorporated to the biotechnology
      industry as host in the production of eukaryotes proteins. Apart from their
      advantages, some genera are the causes of mycosis on man and in some cases, are
      opportunistic pathogens associated to diseases such as HIV. They are also agents
      responsible for the damaging of fresh and elaborated food for human consumption.
      For these reasons, the quick and accurate identification of industrially,
      environmentally and clinically significant yeasts is important. Yeast taxonomy
      has been supported by conventional techniques, based on morphological and
      physiological descriptions of species and genera, but depend on strain culture
      conditions, therefore they have introduced errors in yeast taxonomy and
      originated the duality of their nomenclature. These difficulties have been solved
      with the application of molecular techniques, based on the sequence analysis of
      nucleic acid, specially karyotiping electrophoresis, microsatellite analysis,
      mitochondrial DNA length polymorphism, restriction fragment length polymorphism
      of ribosomal RNA, ramdom amplified polymorphic DNA and low molecular weight RNA.
      In this review all those methods are described, which have allowed the
      development of identification kits for clinical and industrial application for
      the clearance of phylogenetic relationships among species and genera of yeasts of
      biotechnological interest.

PMID- 15458358
TI  - [Genotypes of Candida dubliniensis in clinical isolates].
AB  - Amplification of specific sequences of the ITS1 and ITS2 regions and the
      intervening 5.8S rRNA gene has lead to the identification of four separate
      genotypes in Candida dubliniensis. Using primers specific for each genotype, we
      have studied the prevalence of these genotypes among 68 clinical isolates, mostly
      from Spanish patients infected by HIV. The majority of the isolates tested
      belonged to genotype 1 (97%), while only one isolate each from genotypes 2 (1.5%)
      and 3 (1.5%) were detected in the oral cavity of two patients with HIV infection.

PMID- 15458359
TI  - Phenotypic and genotypic identification of Candida spp. isolated from
      hospitalized patients.
AB  - As candidosis incidence continue to rise, quick laboratory identification of
      Candida species is becoming increasingly important for a growing population of
      patients at-risk. RAPD techniques were used on samples of Candida obtained from
      patients hospitalized at Santa Casa de Misericordia in Belo Horizonte (SCMBH)
      Brazil, from March 1998 to December 2000 and then compared with the results of
      phenotypic identification techniques. Two hundred and forty two yeasts were
      isolated and phenotypically identified as follows: Candida albicans (105),
      Candida tropicalis (62), Candida parapsilosis (28), Candida glabrata (19),
      Candida krusei (8), Candida guilliermondii (5) and Candida spp. (15). Samples
      from the three most frequent species isolated were selected randomly in order to
      compare the phenotypic and genotypic analyses. Genotypic analysis using RAPD
      primer M13 (F/R) displayed the best results of all test samples. There was both
      agreement and consistency between phenotypic and genotypic analysis using RAPD,
      demonstrating that is possible to apply this method for the identification of
      Candida species.

PMID- 15458360
TI  - [Effect of metabolic substances of oral Actinomyces on Candida albicans].
AB  - Actinomyces naeslundii, Actinomyces viscosus and Candida albicans are associated
      with root cavity. The aim of this study was to determine, in vitro, the effect
      produced by the metabolic substances elaborated by Actinomyces naeslundii and
      Actinomyces viscosus on Candida albicans. The strains were isolated of saliva.
      There were used the double plaque diffusion method (DPDM) and the method of
      radial diffusion (MRD). The effect of the time of incubation and of different
      concentrations of metabolic substances elaborated by Actinomyces naeslundii and
      Actinomyces viscosus on the kinetics of growth of C. albicans were studied.
      Later, the nature of the substances produced by the two strains of Actinomyces
      was determined. It was found that there was no inhibition of the growth of C.
      albicans by A. naeslundii and A. viscosus in the DPDM and the MRD. There was
      stimulation of the growth of C. albicans by the two strains of Actinomyces when
      the DPDM was used. In the MRD the results were negative. Metabolic substances
      produced by both species stimulated the growth of C. albicans in low
      concentrations but at high concentrations inhibition was observed. The best
      concentration of the stimulating factor, a protein substance stable to 70 degrees
      C, corresponds to a dilution of 1/80. The inhibition of the growth of C. albicans
      was produced by the decrease of the pH, the higher effect being obtained with the
      dilution 1/5. The metabolic substances produced by A. naeslundii and A. viscosus
      can have both inhibitory and stimulant effects on C. albicans, according to their
      concentration. These metabolic interactions would condition the proportion of C.
      albicans in the oral microbial ecosystems.

PMID- 15458361
TI  - Invasive pulmonary aspergillosis: retrospective case record review.
AB  - Invasive pulmonary aspergillosis is a severe infection, with a sharp increase
      during the last decades. Our study aimed at identification of the epidemiological
      characteristics of invasive pulmonary aspergillosis during a period of four
      years. All clinical records with pulmonary isolation of Aspergillus species were
      reviewed, as a part of surveillance program at Reina Sofia University Hospital,
      from January 1995 to December 1998. Diagnosis of invasive pulmonary aspergillosis
      was based on criteria of Centers for Disease Control and Prevention. Of the 50
      patients identified 78% were males and 44% were current or ex-smokers. Chronic
      respiratory diseases were identified in 64% of them, and 60% were receiving
      immunosuppressives. Twenty percent of our patients had been subjected to lung
      transplantation and 28% to organ transplantation in general. Only 78% had
      received specific antifungal treatment and 56% had fatal prognosis. Our findings
      match with previous studies, apart from the high frequency of lung
      transplantation in our series. We recommend further studies on large prospective
      cohorts.

PMID- 15458362
TI  - [Superficial infections caused by Microsporum canis in humans and animals].
AB  - Dermatophytic infections caused by M. canis in humans and animals have a world
      wide distribution and they are zoonotic. The objective in this work was to know
      the frequency of M. canis infections in humans and pets. We studied our cases
      from January 1994 to December 2002. The human samples were obtained from a
      Dermatological Department in a General Hospital and we registered the next data:
      age, sex, job, and affected area. The animal samples were obtained from a
      mycological veterinary laboratory, and we registered the presence or absence of
      clinical lesions. A total of 46 clinical cases of M. canis infections were
      recorded, 26 female and 20 males: tinea capitis 21, tinea corporis 17, tinea
      pedis five, onychomycosis two, and only one case with tinea faciei. The 46 cases
      with positive culture yield 42 positive samples in KOH. The age range varied from
      2 to 60 years. Among the animals, we studied 461 dogs and found six KOH positive
      (1%) samples and cultured 23 isolates (4.98%): 21 M. canis, one M. gypseum and
      one Trichophyton spp. From the 68 samples of cats, eight (11.76%) were positive
      to KOH, being 26 (38.23%) M. canis isolates. In M. canis infections in humans,
      the age rage was wide with predominance in women. In animals, M. canis isolates
      represented the most dermatophytic infection.

PMID- 15458363
TI  - [Natural presence of Beauveria bassiana (Balsamo) Vuillemin in the sugar cane
      (Saccharum sp. hybrid) in Cuba].
AB  - The natural presence of Beauveria bassiana was determined (Balsamo) Vuillemin
      from insects with mycotic symptoms collected in leaves and in the stalks of sugar
      cane (Saccharum sp. hybrid) in Pinar del Rio, Ciudad de la Habana, Habana,
      Matanzas, Villa Clara, Cienfuegos and Camaguey. The results obtained demonstrate
      the natural presence of the entomopathogen fungus in larvae and chrysalises of
      Diatraea saccharalis (Fabricius) and they suggest the basis for the strategy of
      biological control against this borer.

PMID- 15458364
TI  - [Clinical cases in Medical Mycology. Case No. 7].

PMID- 15458365
TI  - [Clinical cases in Medical Mycology. Case No. 8].

PMID- 15458366
TI  - Effects of the binding of alpha/beta-type small, acid-soluble spore proteins on
      the photochemistry of DNA in spores of Bacillus subtilis and in vitro.
AB  - The main lesion produced in DNA by UV-C irradiation of spores of Bacillus
      subtilis is 5-thyminyl-5,6-dihydrothymine (spore photoproduct [SP]). In contrast,
      cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts
      (6-4PP) are the main photolesions in other cell types. The novel photochemistry
      of spore DNA is accounted for in part by its reduced hydration, but largely by
      the saturation of spore DNA with alpha/beta-type small, acid-soluble spore
      proteins (SASP). Using high-performance liquid chromatography-mass spectrometry
      analysis of the photoproducts, we showed that in wild-type B. subtilis spores (1)
      UV-C irradiation generates almost exclusively SP with little if any CPD and 6
      4PP; (2) the SP generated is approximately 99% of the intrastrand derivative, but
      approximately 1% is in the interstrand form; and (3) there is no detectable
      formation of the SP analog between adjacent C and T residues. UV-C irradiation of
      spores lacking the majority of their alpha/beta-type SASP gave less SP than with
      wild-type spores and significant levels of CPD and 6-4PP. The binding of an
      alpha/beta-type SASP to isolated DNA either in dry films or in aqueous solution
      led to a large decrease in the yield of CPD and 6-4PP, and a concomitant increase
      in the yield of SP, although levels of interstrand photoproducts were extremely
      low.

PMID- 15458367
TI  - Protein kinase C epsilon signals ultraviolet light-induced cutaneous damage and
      development of squamous cell carcinoma possibly through Induction of specific
      cytokines in a paracrine mechanism.
AB  - Protein kinase C (PKC), a family of phospholipid-dependent serine/threonine
      kinases, is not only the major intracellular receptor for the mouse skin tumor
      promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) but also is activated by a
      variety of stress factors including ultraviolet radiation (UVR). PKCepsilon is
      among six isoforms (alpha, delta, epsilon, eta, mu and zeta) expressed in the
      mouse skin. To determine the in vivo functional specificity of PKCepsilon in
      mouse skin carcinogenesis, we generated PKCepsilon transgenic mouse (FVB/N) lines
      224 and 215 that overexpress PKCepsilon protein approximately 8- and 18-fold,
      respectively, over endogenous levels in the basal epidermal cells and cells of
      the hair follicle. PKCepsilon transgenic mice were observed to be highly
      sensitive to the development of papilloma-independent metastatic squamous cell
      carcinoma (mSCC) elicited either by repeated exposure to UVR or by the 7,12
      Dimethylbenzanthracene-TPA tumor promotion protocol. The development of squamous
      cell carcinoma (SCC) appears to be linked to the PKCepsilon-mediated induction of
      cytokine tumor necrosis factor-alpha(TNFalpha). Immunohistochemical analysis for
      the expression of PKCepsilon in the SCC of PKCepsilon transgenic mice revealed
      that PKCepsilon was not expressed in the tumor itself; however, the uninvolved
      tissue surrounding the SCC exhibited intense PKCepsilon expression. Also, human
      SCC, similar to mouse SCC, did not express PKCepsilon in the tumor, whereas the
      surrounding uninvolved epidermis revealed strong PKCepsilon expression. These
      findings in both the PKCepsilon mouse model and human SCC indicate that
      overexpression of PKCepsilon in epidermis may lead to a microenvironment, which
      is suitable for enhancing the development of mSCC by a paracrine mechanism
      involving specific cytokines including TNFalpha.

PMID- 15458368
TI  - Oxidation potentials of human eumelanosomes and pheomelanosomes.
AB  - Eumelanosomes and pheomelanosomes isolated from black and red human hair,
      respectively, were studied by photoelectron emission microscopy (PEEM). PEEM
      images were collected at various wavelengths between 207 and 344 nm, using the
      spontaneous emission output of the Duke OK-4 free electron laser (FEL). Analysis
      of the FEL-PEEM data revealed ionization thresholds of 4.6 and 3.9 eV
      corresponding to oxidation potentials of -0.2 and +0.5 V vs normal hydrogen
      electrode for eumelanosomes and pheomelanosomes, respectively. The difference in
      oxidation potential is attributed to the pigment content of the melanosome,
      namely whether it contains primarily eumelanin and pheomelanin. The effect of
      added melanosomes on the reduction of Fe(III)-cytochrome showed pheomelanosomes
      are stronger reducing agents than eumelanosomes, consistent with the measured
      oxidation potentials. The FEL-PEEM experiment offers to be an important new
      approach for quantifying the effects of age, oxidation and metal accumulation on
      the oxidation potentials of intact melanosomes.

PMID- 15458370
TI  - Critical limb ischemia.

PMID- 15458371
TI  - Lung cancer-related genes in the blood.
AB  - Tumor-related genes can be found circulating in the blood of cancer patients.
      These genes may be derived from circulating cancer cells or from the patient's
      primary tumor directly by a process referred to as "gene shedding." Selective and
      sensitive detection of tumor-related genes in the blood of cancer patients has
      been made possible by the advent of polymerase chain reaction-based technology
      that can detect mutations, polymorphisms, microsatellite instability, loss of
      heterozygosity, and promoter hypermethylation. Several reports have documented
      the clinical potential of using circulating tumor-related genes as a molecular
      marker for the early detection of lung cancer, and as a prognostic tool in these
      patients; larger, prospective studies will be needed to test the feasibility of
      this approach. Certainly, such an approach in lung cancer patients would be
      attractive since it is noninvasive and employs relatively easy and rapid
      methodologies.

PMID- 15458372
TI  - Blunt injury of the innominate artery: a case report and review of literature.
AB  - Innominate artery injury after blunt trauma is uncommon and mostly observed at
      its origin from the aorta. We report here an unusual case of distal innominate
      artery injury associated with acute right subclavian occlusion. MEDLINE search of
      blunt traumatic injury to the innominate artery revealed a total of 132 case
      reports by the end of 2003, including this case report, and all these published
      studies were reviewed.

PMID- 15458373
TI  - Is a metallic stent useful for non resectable esophageal cancer?
AB  - A flexible nitinol stent was inserted to treat malignant stricture of the
      esophagus in 28 patients. Stenting was successful in all 28 patients, leading to
      an improved oral intake that was maintained for >80% of the survival period in 26
      patients. Patients with tumors arising in the esophagus (n=24) were divided into
      two groups to compare complications and prognosis: patients who underwent
      stenting only (n=10); and patients who underwent stenting after radiochemotherapy
      (n=14). Fatal complications associated with stenting were seen in four patients
      (28.6%) who underwent stenting after radiochemotherapy and in one patient (10.0%)
      who underwent stenting only. Although survival was significantly longer for
      patients who underwent prior radiochemotherapy than for patients who did not, the
      incidence of fatal complications tended to be higher. No significant differences
      in background factors other than radiochemotherapy before stenting were observed
      between patients with fatal and non-fatal complications. Stenting was shown to
      represent a useful treatment for malignant stricture of the esophagus, as oral
      intake improved and was maintained for a long period of time in most patients.
      However, incidence of fatal complications was high among patients who underwent
      radiochemotherapy, and caution must be exercised due to the difficulty in
      predicting fatal complications.

PMID- 15458374
TI  - Surgical treatment of lung cancer with vertebral invasion.
AB  - Vertebral body invasion by lung cancer has been problematic due to uncertainty
      regarding a clear surgical resection margin. Therefore, additional
      chemoradiotherapy has been performed to assist clearance of the surgical margin.
      We reviewed our experience of surgical treatment for lung cancer patients with
      vertebral invasion. Between 1982 and 2003, 1,070 patients underwent lung cancer
      surgery at the Nippon Medical School Hospital. Eight patients (0.74%) of this
      group underwent a combined vertebral body and chemoradiotherapy. Seven
      lobectomies and one pneumonectomy with mediastinal lymphadenectomy were
      performed. All patients underwent partial vertebrectomy. The percentage with
      vertebral tumor involvement was 15%. A defect of vertebral cortical bone was
      reinforced with implantation of rib in one patient. There was no postoperative
      mortality. Postoperative complications were pneumonia and arrhythmia. The median
      follow-up period was 19 months (range from 4 to 69.7 months). The overall
      actuarial survivals at 1-year, 3-year and 5-year were 68.6%, 22.9% and 22.9%.
      Local recurrence occurred in three patients and distant metastasis was evident in
      five. Even though the number of patients was small, partial vertebrectomy with
      chemoradiotherapy offer reduction of severe pain and an improved prognosis.
      However, a patient with further progressive disease should be treated with a
      multidisciplinary approach.

PMID- 15458375
TI  - Ultrasonic plaque density of aortic atheroma and stroke in patients undergoing on
      pump coronary bypass surgery.
AB  - OBJECTIVE: The purpose of this study was to determine the relationship between
      the aortic atheromatous plaque echo density and the incidence of postoperative
      stroke or embolic events in patients undergoing on-pump coronary artery bypass
      grafting (CABG). PATIENTS AND METHODS: Three hundred and fourteen patients who
      received on-pump CABG alone were studied. Images of the aortic plaques obtained
      using transesophageal echocardiography were transferred to a computer. Using an
      image analysis program, a histogram for plaques more than 3 mm in thickness was
      obtained through the gray tone frequency distribution of the pixels (0-225). The
      gray scale median (GSM) was used as a measure of plaque echo density. RESULTS:
      Fifty-eight plaques in patients not associated with postoperative stroke or
      embolic events had GSM ranging from 58 to 241 (151.0+/-38.2), while 9 plaques in
      patients associated with stroke or embolic events had GSM ranging from 67 to 130
      (90.6+/-21.3, p<0.001). The incidence of stroke or embolism was 58.3% when GSM of
      plaque was less than 100, while it was 3.6% when plaque GSM was more than 100
      (p<0.001). CONCLUSION: This study indicated that computer analysis of aortic
      atheromatous plaque was useful for selecting patients who had a high risk of
      postoperative stroke or embolism when receiving on-pump CABG, and for decreasing
      the incidence of them.

PMID- 15458376
TI  - Aortoesophageal fistula: alternatives of treatment case report and literature
      review.
AB  - Aortoesophageal fistula (AEF) remains as a life-threatening condition with a high
      rate of morbidity and mortality. It is usually related to aortic or esophageal
      disease, and less commonly foreign body ingestion. In spite of several strategies
      for treatment, there is little consensus regarding the optimal management of this
      entity. In this paper, we present our experience in successfully managing one
      patient with AEF by performing open surgical repair. We also include a discussion
      on criteria for selecting the most appropriate alternative of treatment: open or
      endovascular repair, based on a review of the literature currently available in
      MEDLINE.

PMID- 15458377
TI  - Isolated splenic metastasis from non small cell lung cancer.
AB  - Lung cancer is amongst the commonest cancers in the world. Most patients present
      in advanced stages precluding curative treatment. Distant metastases usually
      occur in the liver, brain, bones and adrenals. Isolated splenic metastases are
      rare and are restricted to anecdotal reports in medical literature. We report a
      middle-aged man who presented to us with locoregionally advanced non small cell
      lung cancer, progressed on neoadjuvant chemotherapy and developed isolated
      splenic metastasis.

PMID- 15458378
TI  - Resection of giant right atrial lymphoma using vacuum-assisted cardiopulmonary
      bypass without snaring the inferior vena cava.
AB  - A 53-year-old man sustained hemodynamic collapse due to a huge right atrial tumor
      and was transferred to our hospital and underwent a life-saving emergency
      operation. The tumor arose from the inferolateral wall of the right atrium,
      occupying almost the whole right atrial cavity and obstructing not only the
      inflow of the right ventricle but also the orifice of the inferior vena cava.
      Venous cannulation via the right atrial wall and placing a snare around the
      inferior vena cava were impossible. With a cardiopulmonary bypass using vacuum
      assisted venous drainage, the tumor was successfully resected and the tricuspid
      valve was replaced with a bioprosthetic valve without snaring the inferior vena
      cava. Postoperative histological examination demonstrated the tumor to be a large
      B-cell non-Hodgkin type malignant lymphoma. When the tumor is large and it is
      difficult to establish total cardiopulmonary bypass, the vacuum-assisted
      cardiopulmonary bypass is a useful option. This can achieve a bloodless operative
      field and is not blocked by the incoming air, due to the venous drainage being
      continually pressure-regulated.

PMID- 15458379
TI  - MRSA aortic valve endocarditis treated by pericardium-lined Dacron patch and
      vancomycin-containing fibrin glue.
AB  - A 40-year-old man was admitted with a diagnosis of MRSA aortic valve
      endocarditis. He was treated conservatively with clindamycin and vancomycin for
      three days, but embolism occurred into the brain and the right lower limb, and
      urgent aortic valve replacement was performed. Resecting an aortic annular
      abscess resulted in a huge defect of the root. The defect was reconstructed with
      a combined patch: a Dacron graft lined with pericardium using vancomycin
      containing fibrin glue. Although complete healing of the infected leg wound was
      slow, no prosthetic valve endocarditis has been detected in the 11 months since
      operation.

PMID- 15458380
TI  - Gastric cancer occurred after coronary artery bypass grafting using the right
      gastroepiploic artery.
AB  - We recently encountered a rare case where gastric cancer developed in the long
      term postoperative stage after coronary artery bypass grafting (CABG) using the
      right gastroepiploic artery (RGEA) and distal partial gastrectomy was performed
      to treat the cancer. The patient was a 64-year-old man. In November 2001, he
      underwent three-vessel CABG, involving bypassing between the right coronary
      artery (RCA) and the RGEA, to treat an old myocardial infarction. In May 2003, he
      was admitted to our hospital because of exacerbation of diabetes mellitus and
      anemia. Gastric endoscopy revealed gastric cancer affecting the pylorus.
      Preoperative abdominal angiography showed the RGEA graft remained well patent. In
      June 2003, he underwent distal partial gastrectomy and regional lymph node
      dissection. Because the RGEA had been freed adequately to the point of
      bifurcation of the gastroduodenal artery during the previous CABG, the RGEA graft
      was preserved during distal partial gastrectomy. When the RGEA is used for CABG,
      it seems advisable to free the RGEA adequately to a point of bifurcation of the
      gastroduodenal artery. If done so, regional lymph node dissection around the RGEA
      is easier to perform when gastric cancer has occurred in these cases, eventually
      reducing the risk for injury of the graft. Following CABG with the RGEA, it seems
      essential to perform periodical checks for gastric cancer to facilitate early
      detection of gastric cancer. The necessity of close follow-up of these cases is
      endorsed by the fact that healing of gastric cancer by endoscopic mucosal
      resection (EMR) is highly probable if the cancer is detected at early stages.

PMID- 15458381
TI  - Aortic root replacement with a freestyle stentless valve for aortitis syndrome
      with ascending aortic aneurysm and aortic regurgitation.
AB  - A 47-year-old woman who had been diagnosed as having aortitis syndrome underwent
      aortic root replacement for an ascending aortic aneurysm and aortic
      regurgitation. Because the patient has been treated with steroids for more than
      20 years, a Freestyle stentless valve was used to avoid the risk of valve
      detachment. There were no complications observed during the postoperative course.
      Although long-term follow-up will be necessary to observe the valve durability,
      the Freestyle stentless valve seems to be useful for aortic root replacement in
      patients at high risk of valve detachment due to aortitis syndrome.

PMID- 15458382
TI  - Pseudoaneurysms of peroneal artery: treatment with transcatheter platinum coil
      embolization.
AB  - This report describes two cases of pseudoaneurysms of the peroneal artery which
      were successfully treated by transluminal platinum coil embolization. A
      pseudoaneurysm developed following a penetrating wound of the calf, and another
      did following thromboembolectomy of the occluded femoropopliteal bypass with a
      Fogarty balloon catheter. The coils were guided and released into the proximal
      peroneal arteries via the placed catheters on the ipsilateral and contralateral
      femoral arteries, respectively. The pseudoaneurysms disappeared in both cases and
      the patients have been doing well until now.

PMID- 15458383
TI  - Coronary artery surgery results 2002 in Japan.
AB  - Over the past 30 years, we have reported on status and outcome of coronary artery
      bypass surgery in Japan. This report is focused on surgery performed last year,
      from January 1 to December 31, 2002. A total of 13,474 cases underwent coronary
      artery bypass grafting (CABG) of these, 12,552 underwent CABG only. The operative
      mortality for patients who underwent CABG only was 2.04% in 2002. Mortality for
      initial elective CABG was 1.02%. These are the best results obtained since
      surveys were started. The percentage of elderly patients undergoing coronary
      artery bypass surgery is rising annually. In 2002, 44.4% of patients were aged 70
      years or older and 6.9% were aged 80 years or older. Mortality in elderly
      patients undergoing initial elective surgery is decreasing, with a mortality of
      1.3% for patients aged 70 years or older and 2.0% for patients aged 80 years or
      older. Since 1996, the number of off-pump CABG (OPCAB) cases remarkably increased
      annually. This less-invasive procedure was performed on 5,628 patients in 2002,
      which is 41.8% of the total number of CABG cases.

PMID- 15458384
TI  - On the mechanism of the increase in cardiolipin biosynthesis and resynthesis in
      hepatocytes during rat liver regeneration.
AB  - CL (cardiolipin) is a major mitochondrial membrane phospholipid important for the
      regulation of mitochondrial function. We examined CL de novo biosynthesis and its
      resynthesis in isolated rat liver hepatocytes prepared 48 h subsequent to two
      thirds PHx (partial hepatectomy). The pool size of CL and its de novo
      biosynthesis from [1,3-(3)H]glycerol were increased 3.3-fold (P<0.05) and 3.1
      fold (P<0.05) respectively in hepatocytes prepared from PHx rats compared with
      sham-operated controls. The reason for the increased CL biosynthesis was a 65%
      increase (P<0.05) in enzymic activity in PGP-S (phosphatidylglycerolphosphate
      synthase), a key enzyme in de novo CL biosynthesis. The increase in PGP-S
      activity was due to a 3-fold increase (P<0.05) of hepatic PGP-S mRNA expression.
      The increase in de novo CL biosynthesis and pool size corresponded to a 2.3-fold
      increase (P<0.05) in the amount of [1-14C]linoleic acid incorporated into CL of
      hepatocytes prepared from PHx rats compared with sham-operated controls,
      indicating an increase in CL resynthesis. The activity of MLCL-AT
      (monolysocardiolipin acyltransferase), a rate-limiting enzyme of CL resynthesis,
      was increased by 43% (P<0.05) in hepatocytes prepared from PHx rats compared with
      sham-operated controls; this result would explain the increase in [1-14C]linoleic
      acid incorporation into CL. The increase in MLCL-AT activity was due to an
      increase in hepatic MLCL-AT protein expression. The results show that CL de novo
      biosynthesis and its resynthesis are increased during liver regeneration.

PMID- 15458385
TI  - Structure-function analysis of water-soluble inhibitors of the catalytic domain
      of exotoxin A from Pseudomonas aeruginosa.
AB  - The mono-ADPRT (mono-ADP-ribosyltransferase), Pseudomonas aeruginosa ETA
      (exotoxin A), catalyses the transfer of ADP-ribose from NAD+ to its protein
      substrate. A series of water-soluble compounds that structurally mimic the
      nicotinamide moiety of NAD+ was investigated for their inhibition of the
      catalytic domain of ETA. The importance of an amide locked into a hetero-ring
      structure and a core hetero-ring system that is planar was a trend evident by the
      IC50 values. Also, the weaker inhibitors have core ring structures that are less
      planar and thus more flexible. One of the most potent inhibitors, PJ34, was
      further characterized and shown to exhibit competitive inhibition with an
      inhibition constant K(i) of 140 nM. We also report the crystal structure of the
      catalytic domain of ETA in complex with PJ34, the first example of a mono-ADPRT
      in complex with an inhibitor. The 2.1 A (1 A=0.1 nm) resolution structure
      revealed that PJ34 is bound within the nicotinamide-binding pocket and forms
      stabilizing hydrogen bonds with the main chain of Gly-441 and to the side-chain
      oxygen of Gln-485, a member of a proposed catalytic loop. Structural comparison
      of this inhibitor complex with diphtheria toxin (a mono-ADPRT) and with PARPs
      [poly(ADP-ribose) polymerases] shows similarity of the catalytic residues;
      however, a loop similar to that found in ETA is present in diphtheria toxin but
      not in PARP. The present study provides insight into the important features
      required for inhibitors that mimic NAD+ and their binding to the mono-ADPRT
      family of toxins.

PMID- 15458386
TI  - Functional studies of human intestinal alkaline sphingomyelinase by
      deglycosylation and mutagenesis.
AB  - Intestinal alk-SMase (alkaline sphingomyelinase) is an ectoenzyme related to the
      NPP (nucleotide phosphodiesterase) family. It has five potential N-glycosylation
      sites and predicated transmembrane domains at both the N- and C-termini. The
      amino acid residues forming the two metal-binding sites in NPP are conserved, and
      those of the active core are modified. We examined the functional changes of the
      enzyme induced by deglycosylation and mutagenesis. Treating alk-SMase cDNA
      transfected COS-7 cells with tunicamycin rendered the expressed enzyme completely
      inactive. Mutations of the five potential N-glycosylation sites individually and
      in combination showed that these sites were all glycosylated and deficient
      glycosylation decreased the enzyme activity. Immunogold labelling showed that the
      wild-type enzyme was mainly located in the plasma membrane, whereas the C
      terminal domain-truncated enzyme was released into the medium. Deglycosylation
      blocked the release of the enzyme that accumulated in endosome-like structures.
      The enzyme activity was also decreased by mutations of the residues forming the
      putative metal-binding sites and the active core. Substitution of the active core
      sequence with that of NPP or mutation of T75 in the core abolished the enzyme
      activity against sphingomyelin but failed to render the enzyme NPP active. Our
      results indicate that alk-SMase activity is severely affected by defective N
      glycosylation and structural alterations of the putative metal-binding sites and
      the predicted active core.

PMID- 15458387
TI  - Direct control of caveolin-1 expression by FOXO transcription factors.
AB  - Protein kinase B can phoshorylate and thereby inactivate the FOXO (forkhead box
      O) family of transcription factors. When active, FOXO factors can bind to DNA in
      promoter sequences and subsequently regulate gene expression. We have used DNA
      microarray analysis to identify potential gene targets of FOXO. In the present
      study we demonstrate that caveolin-1 is directly controlled by FOXO. Firstly,
      caveolin-1 expression was increased upon induction or over-expression of FOXO
      factors at both mRNA and protein levels. Second, we show that endogenous
      regulation of FOXO activity regulates caveolin-1 levels and that this can be
      inhibited by dominant-negative FOXO. Third, FOXO activates transcription from the
      caveolin-1 promoter, and using chromatin immunoprecipitations we demonstrated
      that this activation occurs via direct interaction of FOXO with the promoter.
      Finally, we demonstrate FOXO-mediated attenuation of EGF (epidermal growth
      factor)-induced signalling, which in part is mediated by caveolin-1 expression,
      as suggested by previous studies [Park, Park, Cho, Kim, Ko, Seo and Park (2000)
      J. Biol. Chem. 275, 20847-20852]. These findings suggest a novel mechanism by
      which FOXO factors can exert their cellular effects via transcriptional
      activation of caveolin-1.

PMID- 15458388
TI  - Recognition and processing of a nuclear-encoded polyprotein precursor by
      mitochondrial processing peptidase.
AB  - The nuclear-encoded protein RPS14 (ribosomal protein S14) of rice mitochondria is
      synthesized in the cytosol as a polyprotein consisting of a large N-terminal
      domain comprising preSDHB (succinate dehydrogenase B precursor) and the C
      terminal RPS14. After the preSDHB-RPS14 polyprotein is transported into the
      mitochondrial matrix, the protein is processed into three peptides: the N
      terminal prepeptide, the SDHB domain and the C-terminal mature RPS14. Here we
      report that the general MPP (mitochondrial processing peptidase) plays an
      essential role in processing of the polyprotein. Purified yeast MPP cleaved both
      the N-terminal presequence and the connector region between SDHB and RPS14.
      Moreover, the connector region was processed more rapidly than the presequence.
      When the site of cleavage between SDHB and RPS14 was determined, it was located
      in an MPP processing motif that has also been shown to be present in the N
      terminal presequence. Mutational analyses around the cleavage site in the
      connector region suggested that MPP interacts with multiple sites in the region,
      possibly in a similar manner to the interaction with the N-terminal presequence.
      In addition, MPP preferentially recognized the unfolded structure of preSDHB
      RPS14. In mitochondria, MPP may recognize the stretched polyprotein during
      passage of the precursor through the translocational apparatus in the inner
      membrane, and cleave the connecting region between the SDHB and RPS14 domains
      even before processing of the presequence.

PMID- 15458389
TI  - Involvement of a cytoplasmic-tail serine cluster in urotensin II receptor
      internalization.
AB  - Most G-protein-coupled receptors that undergo agonist-dependent internalization
      require the presence of specific cytoplasmic-tail residues to initiate
      interactions with proteins of the endocytic machinery. Here we show that the UT
      receptor (urotensin II receptor) undergoes internalization, and that specific
      serine residues of the receptor's cytoplasmic tail participate in this process.
      We first observed a time-dependent increase in internalization of the UT receptor
      expressed in COS-7 cells following binding of the agonist urotensin II. This
      sequestration was significantly reduced in the presence of sucrose, demonstrating
      that the agonist-activated UT receptor is internalized in part by clathrin-coated
      pits. Moreover, the sequestered receptor was co-localized in endocytic vesicles
      with beta-arrestin1 and beta-arrestin2. To assess whether specific regions of the
      receptor's cytoplasmic tail were involved in internalization, five UT receptor
      mutants were constructed. In four constructs the receptor's cytoplasmic tail was
      truncated at various positions (UTDelta367, UTDelta363, UTDelta350 and
      UTDelta336), and in the other four adjacent serine residues at positions 364-367
      were replaced by Ala (Mut4S). Each mutant, except UTDelta367, demonstrated a
      significantly reduced internalization rate, thereby revealing the importance of
      specific serine residues within the cytoplasmic tail of the UT receptor for its
      ability to be internalized efficiently.

PMID- 15458391
TI  - Prevalence of obesity in Uruguay.

PMID- 15458392
TI  - Aetiology of obesity: a striving after wind?
AB  - The current global epidemic of obesity is fuelled by a constant, unidirectional
      adverse effect on energy balance that exceeds the adaptive capacity of the
      system. The individual response to this environmental pressure is under the
      control of a variety of genes, which not only interacts with environmental
      factors but also with one another. Since the discovery that adipocytes may
      produce and secrete hormones, the adipose tissue has taken on increasing
      importance in the regulation of energy balance. Indeed, the pathogenesis of
      obesity, once regarded as so obvious and simple, is becoming one of the most
      complex in medical practice. From a clinical perspective, obesity is associated
      with a remarkably broad spectrum of health complications and, over the years,
      obesity-related mortality has consistently increased. From a theoretical
      viewpoint, the growing complexity of factors affecting the liability to obesity,
      the inconsistency of scientific results, the lack of consensus among scientists,
      and so forth, obstruct our efforts to unravel the aetiology of obesity. Is the
      field of obesity research merely a striving after wind, and nothing more?

PMID- 15458393
TI  - Substrate metabolism, nutrient balance and obesity development in children and
      adolescents: a target for intervention?
AB  - Obesity results from the organism's inability to maintain energy balance over a
      long term. Childhood obesity and its related factors and pathological
      consequences tend to persist into adulthood. A cluster of factors, including high
      energy density in the diet (high fat intake), low energy expenditure, and
      disturbed substrate oxidation, favour the increase in fat mass. Oxidation of
      three major macronutrients and their roles in the regulation of energy balance,
      particularly in children and adolescents, are discussed. Total glucose oxidation
      is not different between obese and lean children; exogenous glucose utilization
      is higher whereas endogenous glucose utilization is lower in obese compared with
      lean children. Carbohydrate composition of the diet determines carbohydrate
      oxidation regardless of fat content of the diet. Both exogenous and endogenous
      fat oxidation are higher in obese than in lean subjects. The influence of high
      fat intake on accumulation of fat mass is operative rather over a long term.
      Several future directions are addressed, such that a combination of increased
      physical activity and modification in diet composition, in terms of energy
      density and glycemic index, is recommended for children and adolescents.

PMID- 15458394
TI  - Adipose tissue: new therapeutic targets from molecular and genetic studies--IASO
      Stock Conference 2003 report.
AB  - This review highlights the presentations and discussions held during the 2003
      Stock Conference in Lisbon focussed on the identification of new therapeutic
      targets for the treatment of obesity and identified through molecular and genetic
      studies. Transcription factors and their cofactors, signalling pathways and new
      insights provided by cellular and genetic studies were discussed as potential new
      avenues to modulate adipocyte formation and function.

PMID- 15458395
TI  - Direct effects of sex steroid hormones on adipose tissues and obesity.
AB  - Sex steroid hormones are involved in the metabolism, accumulation and
      distribution of adipose tissues. It is now known that oestrogen receptor,
      progesterone receptor and androgen receptor exist in adipose tissues, so their
      actions could be direct. Sex steroid hormones carry out their function in adipose
      tissues by both genomic and nongenomic mechanisms. In the genomic mechanism, the
      sex steroid hormone binds to its receptor and the steroid-receptor complex
      regulates the transcription of given genes. Leptin and lipoprotein lipase are two
      key proteins in adipose tissues that are regulated by transcriptional control
      with sex steroid hormones. In the nongenomic mechanism, the sex steroid hormone
      binds to its receptor in the plasma membrane, and second messengers are formed.
      This involves both the cAMP cascade and the phosphoinositide cascade. Activation
      of the cAMP cascade by sex steroid hormones would activate hormone-sensitive
      lipase leading to lipolysis in adipose tissues. In the phosphoinositide cascade,
      diacylglycerol and inositol 1,4,5-trisphosphate are formed as second messengers
      ultimately causing the activation of protein kinase C. Their activation appears
      to be involved in the control of preadipocyte proliferation and differentiation.
      In the presence of sex steroid hormones, a normal distribution of body fat
      exists, but with a decrease in sex steroid hormones, as occurs with ageing or
      gonadectomy, there is a tendency to increase central obesity, a major risk for
      cardiovascular disease, type 2 diabetes and certain cancers. Because sex steroid
      hormones regulate the amount and distribution of adipose tissues, they or adipose
      tissue-specific selective receptor modulators might be used to ameliorate
      obesity. In fact, hormone replacement therapy in postmenopausal women and
      testosterone replacement therapy in older men appear to reduce the degree of
      central obesity. However, these therapies have numerous side effects limiting
      their use, and selective receptor modulators of sex steroid hormones are needed
      that are more specific for adipose tissues with fewer side effects.

PMID- 15458396
TI  - Evaluating commercial weight loss programmes: an evolution in outcomes research.
AB  - The increasing prevalence of obesity has been mirrored by a parallel increase in
      the number of commercial weight loss programmes. Research evaluating these
      programmes is meagre, however, compared to the numbers treated. Reluctance of
      commercial weight loss programmes to meaningfully evaluate their weight loss
      efficacy may arise from fear that competitors will use the results against them.
      Evaluation of commercial weight loss programmes usually progresses from
      testimonials, often by famous people who were successful, to uncontrolled studies
      of past participants evaluated either by the programme itself or by an outside
      entity. The gold standard, however, is a scientifically rigorous, controlled
      study of the programme conducted by an independent entity. Such a study,
      published in a peer-reviewed journal, can gain credibility for a programme, as it
      did with Slim Fast, if the results are positive, or herald the end of the
      programme, as it was with Simeons human chorionic gonadotropin injection clinics.
      This review of the evolution of the evaluation process of commercial weight loss
      programmes leads us to conclude that consumers are likely to demand greater
      scientific rigour in the future, a change that will favour informed choice and
      discourage the practice of unrealistic advertising that raises false hopes.

PMID- 15458397
TI  - Psychiatric medication-induced obesity: treatment options.
AB  - A majority of psychiatric medications are known to generate weight gain and
      ultimately obesity in some patients. The authors undertook a comprehensive
      literature review in order to provide a better understanding of novel treatment
      options in regards to alleviating weight gained by use of antidepressants,
      antipsychotics, and mood stabilizers. There are no agents for management of this
      weight gain approved by the Food and Drug Administration (FDA), and existing
      studies on options are mainly uncontrolled, small-scale projects with limited
      power to produce coherent conclusions. There is a clear need for larger studies
      on existing options, and future psychotropics without these side-effects are
      currently in the pipeline.

PMID- 15458398
TI  - Weight loss strategies--a change of focus is required.

PMID- 15458400
TI  - A network of net-workers: report of the Euresco conference on 'Bacterial Neural
      Networks' held at San Feliu (Spain) from 8 to 14 May 2004.
AB  - In May 2004, over 100 bacteriologists from 19 different countries discussed
      recent progress in identification and understanding of individual signal transfer
      mechanisms in bacteria and in the mutual interactions between these systems to
      form a functional living cell. The meeting was held in San Feliu and supported by
      ESF and EMBO. In part through the extensive sequencing efforts of the past few
      years, the bulk of the bacterial signal transfer systems have been resolved and
      their detailed characterization is revealing such characteristics as signal
      specificity, signalling rate constants, molecular interaction affinities,
      subcellular localization, etc., which should provide a solid basis to a
      computational extension of this field of studies. In parallel, the new genomics
      techniques are providing tools to characterize the way a collection of such
      systems interact in an individual cell, to give rise to 'life'. Systems theory
      provides rational and convenient ways to bring order to the wide range of
      observables thus obtained. Ultimately, the performance of engineered design will
      have to prove whether or not we know enough about the processes involved.

PMID- 15458401
TI  - Recognition of iron-free siderophores by TonB-dependent iron transporters.
AB  - TonB-dependent iron transporters reside in the outer membranes of Gram-negative
      bacteria, transporting ferric-complexes into the periplasm by a mechanism
      requiring proton motive force and an integral inner membrane complex, TonB-ExbB
      ExbD. Certain TonB-dependent transporters contain an additional domain at the N
      terminus, which interacts with an inner membrane regulatory protein and a
      cytoplasmic sigma factor to induce transcription of iron transport genes when a
      ferric-ligand is bound at the extracellular surface of the transporter. Transport
      of the ferric-ligand is apparently not necessary for transcription induction.
      Recent biophysical and crystallographic experiments have shown that this subclass
      of TonB-dependent iron transporters can bind iron-free ligands, whereas only the
      ferric-ligands are transported into the periplasm. This review focuses on the
      ligand binding properties of these transporters and includes a discussion of the
      biological function of the additional domain, the mechanism of transcription
      induction and the mechanism of ferric-ligand transport.

PMID- 15458402
TI  - Molecular pathogenesis of neonatal group B streptococcal infection: no longer in
      its infancy.
AB  - The process of human infection by group B Streptococcus (GBS) is complex and
      multifactorial. While this bacterium has adapted well to asymptomatic
      colonization of adult humans, it remains a potentially devastating pathogen to
      susceptible infants. Advances in molecular techniques and refinement of in vitro
      and in vivo model systems have elucidated key elements of the pathogenic process,
      from initial attachment to the maternal vaginal epithelium to penetration of the
      newborn blood-brain barrier. Sequencing of two complete GBS genomes has provided
      additional context for interpretation of experimental data and comparison to
      other well-studied pathogens. Here we review recent discoveries regarding GBS
      virulence mechanisms, many of which are revealed or magnified by the unique
      circumstances of the birthing process and the deficiencies of neonatal immune
      defence. Appreciation of the formidable array of GBS virulence factors
      underscores why this bacterium remains at the forefront of neonatal pathogens.

PMID- 15458403
TI  - Novel substitutions in the sigma54-dependent activator DctD that increase
      dependence on upstream activation sequences or uncouple ATP hydrolysis from
      transcriptional activation.
AB  - Sinorhizobium meliloti DctD is an activator of sigma(54)-RNA polymerase
      holoenzyme and member of the AAA+ superfamily of ATPases. DctD uses energy
      released from ATP hydrolysis to stimulate the isomerization of a closed promoter
      complex to an open complex. DctD binds to upstream activation sequences (UAS) and
      contacts the closed complex through DNA looping to activate transcription, but
      the UAS is not essential for activation if DctD is expressed at higher than
      normal levels. Introduction of specific substitutions within or near the
      conserved ESELFG motif in the C3 region of a truncated, constitutively active
      form of DctD produced several mutant forms of the protein that had increased
      dependence on the UAS for activation. Removing the DNA-binding domain from one
      UAS-dependent mutant and from one activation-deficient mutant significantly
      increased transcriptional activation, indicating that the DNA-binding domain
      interfered with the activities of these mutant proteins. A UAS-dependent mutant
      with a P315L substitution in the C6 region was identified from a genetic screen.
      Alanine scanning mutagenesis of conserved amino acid residues around Pro-315
      produced two additional UAS-dependent mutants as well as several mutants that
      failed to activate transcription but retained ATPase activity. In contrast to the
      two mutant proteins with substitutions in the C3 region, removal of the DNA
      binding domain from the mutant proteins with substitutions in the C6 region did
      not stimulate their activity. The residues in the C6 region that were altered are
      in a probable hinge region between the alpha/beta and alpha-helical subdomains of
      the AAA+ domain. The alpha-helical subdomain contains the sensor II helix that
      has been implicated in other AAA+ proteins as sensing changes in the nucleotide
      during the hydrolysis cycle. Substitutions in the hinge region may have abolished
      nucleotide sensing by interfering with subdomain interactions, altering the
      relative orientation of the sensor II helix or interfering with oligomerization
      of the protein.

PMID- 15458404
TI  - Versatility of the carboxy-terminal domain of the alpha subunit of RNA polymerase
      in transcriptional activation: use of the DNA contact site as a protein contact
      site for MarA.
AB  - The transcriptional activator, MarA, interacts with RNA polymerase (RNAP) to
      activate promoters of the mar regulon. Here, we identify the interacting surfaces
      of MarA and of the carboxy-terminal domain of the alpha subunit of RNAP (alpha
      CTD) by NMR-based chemical shift mapping. Spectral changes were monitored for a
      MarA-DNA complex upon titration with alpha-CTD, and for alpha-CTD upon titration
      with MarA-DNA. The mapping results were confirmed by mutational studies and
      retention chromatography. A model of the ternary complex shows that alpha-CTD
      uses a '265-like determinant' to contact MarA at a surface distant from the DNA.
      This is unlike the interaction of alpha-CTD with the CRP or Fis activators where
      the '265 determinant' contacts DNA while another surface of the same alpha-CTD
      molecule contacts the activator. These results reveal a new versatility for alpha
      CTD in transcriptional activation.

PMID- 15458405
TI  - Cell cycle-dependent abundance, stability and localization of FtsA and FtsQ in
      Caulobacter crescentus.
AB  - Coordination between cell division and DNA replication is ensured by checkpoints
      that act through proteins required for cell division. Following a block in DNA
      replication, transcription of the cell division progression genes ftsA and ftsQ
      is prevented in Caulobacter crescentus. One requirement for this checkpoint is
      that FtsA and/or FtsQ should be limiting for division in the next cell cycle. We
      show that the number of FtsA and FtsQ molecules fluctuates such that their
      concentration is low in swarmer and stalked cells, peaks in pre-divisional cells,
      and then dramatically decreases after cell division. Despite constitutive
      expression from an inducible promoter, FtsA and FtsQ levels still vary during the
      cell cycle, and the half-life of FtsA increases from 13 min in swarmer cells to
      55 min in stalked cell types, confirming cell type-specific degradation. The post
      division degradation of FtsA and FtsQ in swarmer cells reduces their
      concentration to 7% and 10% of their maximal level, respectively, strongly
      suggesting that de novo synthesis of both proteins is required for each division
      cycle. The localization of FtsA and FtsQ is also cell type-specific. FtsA and
      FtsQ are recruited to the midcell during a short period in late pre-divisional
      cells, consistent with the demonstrated requirement of FtsA for late stages of
      cell division. As previously reported for FtsZ, constitutive expression of FtsA
      causes cell division defects. These results indicate that the tight control of
      FtsA, and probably FtsQ, by cell cycle transcription, proteolysis, and
      localization are critical for optimal cell division and the coordination of cell
      division with the DNA replication cycle.

PMID- 15458406
TI  - HmsP, a putative phosphodiesterase, and HmsT, a putative diguanylate cyclase,
      control Hms-dependent biofilm formation in Yersinia pestis.
AB  - The Hms(+) phenotype of Yersinia pestis promotes the binding of haemin or Congo
      red (CR) to the cell surface at temperatures below 34 degrees C. We previously
      demonstrated that temperature regulation of the Hms(+) phenotype is not
      controlled at the level of transcription. Instead, HmsH, HmsR and HmsT are
      degraded upon a temperature shift from 26 degrees C to 37 degrees C. We used
      random transposon mutagenesis to identify new genes involved in the temperature
      regulated expression of the Hms phenotype. One of these genes, which we
      designated hmsP, encodes a putative phosphodiesterase with a conserved EAL motif.
      Mutations in hmsP caused formation of red colonies on CR plates at 26 degrees C
      and 37 degrees C. Strains complemented with hmsP(+) on a plasmid form white
      colonies at both temperatures. We used a crystal violet assay and confocal laser
      scanning microscopy to demonstrate Hms-dependent biofilm formation by Y. pestis
      cells. Y. pestis Hms(+) strains grown at 26 degrees C but not at 37 degrees C
      form a biofilm on borosilicate glass surfaces. Strains that either overexpress
      HmsT (a GGDEF domain protein) or have a mutation in hmsP produced an extremely
      thick biofilm. Alanine substitutions for each of the GGEE residues (amino acids
      296-299) of HmsT as well as the E506 and L508 residues of HmsP caused a loss of
      function. We propose that HmsT and HmsP together control the amount of biofilm
      produced in Y. pestis. Degradation of HmsT at 37 degrees C may be a critical
      factor in controlling the temperature-dependent expression of the Hms biofilm.

PMID- 15458407
TI  - Identification of SpyA, a novel ADP-ribosyltransferase of Streptococcus pyogenes.
AB  - Streptococcus pyogenes, the aetiological agent of both respiratory and skin
      infections, produces numerous exotoxins to establish infection. This report
      identifies a new exotoxin produced by this organism, termed SpyA, for S.
      pyogenesADP-ribosylating toxin. SpyA, MW 24.9, has amino acid identity with the
      ADP-riboslytransferases (ADPRTs) Staphylococcus aureus EDIN and Clostridium
      botulinum C3. Recombinant SpyA was able to hydrolyse beta-NAD(+), and this
      activity was dependent on a glutamate at position 187. SpyA has a putative
      biglutamate active site, and similar to most biglutamate ADPRTs, was able to ADP
      ribosylate poly-l-arginine. SpyA modified numerous proteins in both CHO and HeLa
      cell lysates. Two-dimesional gel analysis and MALDI-TOF MS analysis of modified
      proteins indicated that vimentin, tropomyosin and actin, all cytoskeletal
      proteins, are targets. Expression of spyA in HeLa cells resulted in loss of actin
      microfilaments. We hypothesize that SpyA is produced by S. pyogenes to disrupt
      cytoskeletal structures and promote colonization of the host.

PMID- 15458408
TI  - Positioning of the MinE binding site on the MinD surface suggests a plausible
      mechanism for activation of the Escherichia coli MinD ATPase during division site
      selection.
AB  - Division site selection in Escherichia coli requires that the MinD protein
      interact with itself and with MinC and MinE. MinD is a member of the NifH-ArsA
      Par-MinD subgroup of ATPases. The MinE-MinD interaction results in activation of
      MinD ATPase activity in the presence of membrane vesicles. The sites within MinD
      responsible for its interaction with MinC and MinE were studied by site-directed
      mutagenesis and yeast two-hybrid analysis, guided by the known three-dimensional
      structure of MinD proteins. This provided evidence that MinC and MinE bind to
      overlapping sites on the MinD surface. The results also suggested that MinE and
      the invariant Lys11 residue in the ATPase P-loop of MinD compete for binding to a
      common site within the MinD structure, thereby providing a plausible structural
      basis for the ability of MinE to activate the ATPase activity of MinD.

PMID- 15458409
TI  - Food vacuole-associated lipid bodies and heterogeneous lipid environments in the
      malaria parasite, Plasmodium falciparum.
AB  - The malaria parasite Plasmodium falciparum induces a sixfold increase in the
      phospholipid content of infected erythrocytes during its intraerythrocytic
      growth. We have characterized the lipid environments in parasitized erythrocyte
      using the hydrophobic probe, Nile Red. Spectral imaging with a confocal
      microscope revealed heterogeneous lipid environments in parasite-infected
      erythrocytes. An insight into the nature of these environments was gained by
      comparing these spectra with those of triacylglycerol/phospholipid emulsions and
      phospholipid membranes. Using this approach, we identified a population of
      intensely stained particles of a few hundred nanometers in size that are closely
      associated with the digestive vacuole of the parasite and appear to be composed
      of neutral lipids. Electron microscopy and isolation of food vacuoles confirmed
      the size of these particles and their intimate association respectively. Lipid
      analysis suggests that these neutral lipid bodies are composed of di- and
      triacylgycerols and may represent storage organelles for lipid intermediates that
      are generated during digestion of phospholipids in the food vacuole. Mono-, di-
      and triacylglycerol suspensions promote beta-haematin formation, suggesting that
      these neutral lipid bodies, or their precursors, may also be involved in haem
      detoxification. We also characterized other compartments of the infected
      erythrocyte that were stained less intensely with the Nile Red probe. Both the
      erythrocyte membrane and the parasite membrane network exhibit red shifts
      compared with the neutral lipid bodies that are consistent with cholesterol-rich
      and cholesterol-poor membranes respectively. Ratiometric imaging revealed more
      subtle variations in the lipid environments within the parasite membrane network.

PMID- 15458410
TI  - Positive supercoiling is generated in the presence of Escherichia coli SeqA
      protein.
AB  - In Escherichia coli, the SeqA protein is known as a negative regulator of
      chromosome replication. This protein is also suggested to have a role in
      chromosome organization. SeqA preferentially binds to hemi-methylated DNA and is
      by immunofluorescence microscopy seen as foci situated at the replication
      factories. Loss of SeqA leads to increased negative supercoiling of the DNA. We
      show that purified SeqA protein bound to fully methylated, covalently closed or
      nicked circular DNA generates positive supercoils in vitro in the presence of
      topoisomerase I or ligase respectively. This means that binding of SeqA changes
      either the twist or the writhe of the DNA. The ability to affect the topology of
      DNA suggests that SeqA may take part in the organization of the chromosome in
      vivo. The topology change performed by SeqA occurred also on unmethylated
      plasmids. It is, however, reasonable to suppose that in vivo the major part of
      such activity is performed on hemi-methylated DNA at the replication factories
      and presumably forms the basis for the characteristic SeqA foci observed by
      fluorescence microscopy.

PMID- 15458411
TI  - Regulation of GlnK activity: modification, membrane sequestration and proteolysis
      as regulatory principles in the network of nitrogen control in Corynebacterium
      glutamicum.
AB  - P(II)-type signal transduction proteins play a central role in nitrogen
      regulation in many bacteria. In response to the intracellular nitrogen status,
      these proteins are rendered in their function and interaction with other proteins
      by modification/demodification events, e.g. by phosphorylation or uridylylation.
      In this study, we show that GlnK, the only P(II)-type protein in Corynebacterium
      glutamicum, is adenylylated in response to nitrogen starvation and deadenylylated
      when the nitrogen supply improves again. Both processes depend on the GlnD
      protein. As shown by mutant analyses, the modifying activity of this enzyme is
      located in the N-terminal part of the enzyme, while demodification depends on its
      C-terminal domain. Besides its modification status, the GlnK protein changes its
      intracellular localization in response to changes of the cellular nitrogen
      supply. While it is present in the cytoplasm during nitrogen starvation, the GlnK
      protein is sequestered to the cytoplasmic membrane in response to an ammonium
      pulse following a nitrogen starvation period. About 2-5% of the GlnK pool is
      located at the cytoplasmic membrane after ammonium addition. GlnK binding to the
      cytoplasmic membrane depends on the ammonium transporter AmtB, which is encoded
      in the same transcriptional unit as GlnK and GlnD, the amtB-glnK-glnD operon. In
      contrast, the structurally related methylammonium/ammonium permease AmtA does not
      bind GlnK. The membrane-bound GlnK protein is stable, most likely to inactivate
      AmtB-dependent ammonium transport in order to prevent a detrimental futile cycle
      under post-starvation ammonium-rich conditions, while the majority of GlnK is
      degraded within 2-4 min. Proteolysis in the transition period from nitrogen
      starvation to nitrogen-rich growth seems to be specific for GlnK; other proteins
      of the nitrogen metabolism, such as glutamine synthetase, or proteins unrelated
      to ammonium assimilation, such as enolase and ATP synthase subunit F(1)beta, are
      stable under these conditions. Our analyses of different mutant strains have
      shown that at least three different proteases influence the degradation of GlnK,
      namely FtsH, the ClpCP and the ClpXP protease complex.

PMID- 15458412
TI  - Expression of nitrite reductase in Nitrosomonas europaea involves NsrR, a novel
      nitrite-sensitive transcription repressor.
AB  - Production of nitric oxide (NO) and nitrous oxide (N(2)O) by ammonia (NH(3))
      oxidizing bacteria in natural and man-made habitats is thought to contribute to
      the undesirable emission of NO and N(2)O into the earth's atmosphere. The NH(3)
      oxidizing bacterium Nitrosomonas europaea expresses nitrite reductase (NirK), an
      enzyme that has so far been studied predominantly in heterotrophic denitrifying
      bacteria where it is involved in the production of these nitrogenous gases. The
      finding of nirK homologues in other NH(3)-oxidizing bacteria suggests that NirK
      is widespread among this group; however, its role in these nitrifying bacteria
      remains unresolved. We identified a gene, nsrR, which encodes a novel nitrite
      (NO(2) (-))-sensitive transcription repressor that plays a pivotal role in the
      regulation of NirK expression in N. europaea. NsrR is a member of the Rrf2 family
      of putative transcription regulators. NirK was expressed aerobically in response
      to increasing concentrations of NO(2) (-) and decreasing pH. Disruption of nsrR
      resulted in the constitutive expression of NirK. NsrR repressed transcription
      from the nirK gene cluster promoter (P(nir)), the activity of which correlated
      with NirK expression. Reconstruction of the NsrR-P(nir) system in Escherichia
      coli revealed that repression by NsrR was reversed by NO(2) (-) in a pH-dependent
      manner. The findings are consistent with the hypothesis that N. europaea
      expresses NirK as a defence against the toxic NO(2) (-) that is produced during
      nitrification.

PMID- 15458413
TI  - Phase variable desialylation of host proteins that bind to Streptococcus
      pneumoniae in vivo and protect the airway.
AB  - Most clinical isolates of Streptococcus pneumoniae consist of heterogeneous
      populations of at least two colony phenotypes, opaque and transparent, selected
      for in the bloodstream and nasopharynx, respectively. Microarray analysis
      revealed 24 orfs that demonstrated differences in expression greater than twofold
      between variants of independent strains. Twenty-one of these showed increased
      expression in the transparent variants, including 11 predicted to be involved in
      sugar metabolism. A single genomic region contains seven of these loci including
      the gene that encodes the neuraminidase, NanA. In contrast to previous studies,
      there was no contribution of NanA to adherence of S. pneumoniae to epithelial
      cells or colonization in an animal model. However, we observed NanA-dependent
      desialylation of human airway components that bind to the organism and may
      mediate bacterial clearance. Targets of desialylation included human lactoferrin,
      secretory component, and IgA2 that were shown to be present on the surface of the
      pneumococcus in vivo during pneumococcal pneumonia. The efficiency of
      desialylation was increased in the transparent variants and enhanced for host
      proteins binding to the surface of S. pneumoniae. Because deglycosylation affects
      the function of many host proteins, NanA may contribute to a protease-independent
      mechanism to modify bound targets and facilitate enhanced survival of the
      bacterium.

PMID- 15458414
TI  - Identification of ComW as a new component in the regulation of genetic
      transformation in Streptococcus pneumoniae.
AB  - Regulation of competence for genetic transformation in Streptococcus pneumoniae
      depends on a quorum-sensing system, genes involved in DNA uptake and
      recombination and a link between these two gene sets. The alternative sigma
      factor ComX provides this link. ComE, the response regulator of the quorum
      sensing system, is required for expression of ComX and other early genes.
      However, an unknown ComE-dependent regulator is also required for competence when
      comX is expressed under control of the raffinose-responsive promoter of the aga
      operon. The gene comW (SP0018) is required for a high level of competence and is
      regulated by the quorum-sensing system, but its function is unknown. To explore
      its role further, comW was cloned into the multicopy plasmid pMSP3535, under the
      control of a nisin-inducible promoter (P(N)), and transformed into pneumococcal
      strains containing a raffinose-inducible comX gene (P(R)::comX). Further
      introduction of a comE deletion blocked the endogenous CSP signal transduction
      pathway. In the resulting strain, competence was independent of CSP but depended
      on treatment with both nisin and raffinose, showing that coexpression of comW and
      comX complemented the comE deficiency. ComX protein accumulation and expression
      of a late competence gene in the above strain support the conclusion that ComW is
      a new positive factor involved in competence regulation.

PMID- 15458415
TI  - Post-proteomic identification of a novel phage-encoded streptodornase, Sda1, in
      invasive M1T1 Streptococcus pyogenes.
AB  - The M1T1 strain remains the most frequently isolated strain from group A
      streptococcal (GAS) infection cases worldwide. We previously reported that M1T1
      differs from the fully sequenced M1 SF370 strain. To better understand the reason
      for the persistence and increased virulence of M1T1, we analysed its secreted
      proteome and identified two virulence proteins that are not present in the
      sequenced M1 SF370 strain: streptococcal pyrogenic exotoxin A (SpeA) and a
      streptodornase D (SdaD) homologue. In the present study, we determined the
      nucleotide sequence of the M1T1 streptodornase and found that its deduced amino
      acid sequence is highly similar to other streptococcal streptodornases, and is
      most closely related to the SdaD of GAS strain M49. M1T1 Sda shares two highly
      conserved domains with several DNases and putative DNases in streptococci;
      however, it possesses a unique C-terminal amino acid sequence. Thus, we named the
      protein Sda1, and we detected the presence of the sda1 gene in 16 M1T1 clinical
      isolates. The cloned and expressed Sda1 degrades both streptococcal and mammalian
      DNA at physiological pH. Amino acid similarity analyses of known GAS
      deoxyribonucleases suggest that Sda1 may be a chimeric protein created through
      recombination events. Moreover, a natural mutation that resulted in longer Sda1
      and SdaD as compared to other GAS DNases was found to confer increased activity
      on the protein. Analysis of the sequences flanking sda1 determined that it is
      carried by a prophage or a prophage-like element inserted in the tRNA-Ser gene of
      M1T1 GAS. Ongoing studies in our laboratory aim to determine the contribution of
      Sda1 to the virulence of this globally disseminated M1T1 strain.

PMID- 15458416
TI  - RNase HI overproduction is required for efficient full-length RNA synthesis in
      the absence of topoisomerase I in Escherichia coli.
AB  - It has long been known that Escherichia coli cells deprived of topoisomerase I
      (topA null mutants) do not grow. Because mutations reducing DNA gyrase activity
      and, as a consequence, negative supercoiling, occur to compensate for the loss of
      topA function, it has been assumed that excessive negative supercoiling is
      somehow involved in the growth inhibition of topA null mutants. However, how
      excess negative supercoiling inhibits growth is still unknown. We have previously
      shown that the overproduction of RNase HI, an enzyme that degrades the RNA
      portion of an R-loop, can partially compensate for the growth defects because of
      the absence of topoisomerase I. In this article, we have studied the effects of
      gyrase reactivation on the physiology of actively growing topA null cells. We
      found that growth immediately and almost completely ceases upon gyrase
      reactivation, unless RNase HI is overproduced. Northern blot analysis shows that
      the cells have a significantly reduced ability to accumulate full-length mRNAs
      when RNase HI is not overproduced. Interestingly, similar phenotypes, although
      less severe, are also seen when bacterial cells lacking RNase HI activity are
      grown and treated in the same way. All together, our results suggest that excess
      negative supercoiling promotes the formation of R-loops, which, in turn, inhibit
      RNA synthesis.

PMID- 15458417
TI  - Widespread distribution of a lexA-regulated DNA damage-inducible multiple gene
      cassette in the Proteobacteria phylum.
AB  - The SOS response comprises a set of cellular functions aimed at preserving
      bacterial cell viability in front of DNA injuries. The SOS network, negatively
      regulated by the LexA protein, is found in many bacterial species that have not
      suffered major reductions in their gene contents, but presents distinctly
      divergent LexA-binding sites across the Bacteria domain. In this article, we
      report the identification and characterization of an imported multiple gene
      cassette in the Gamma Proteobacterium Pseudomonas putida that encodes a LexA
      protein, an inhibitor of cell division (SulA), an error-prone polymerase (DinP)
      and the alpha subunit of DNA polymerase III (DnaE). We also demonstrate that
      these genes constitute a DNA damage-inducible operon that is regulated by its own
      encoded LexA protein, and we establish that the latter is a direct derivative of
      the Gram-positive LexA protein. In addition, in silico analyses reveal that this
      multiple gene cassette is also present in many Proteobacteria families, and that
      both its gene content and LexA-binding sequence have evolved over time,
      ultimately giving rise to the lexA lineage of extant Gamma Proteobacteria.

PMID- 15458418
TI  - New enzymes involved in aerobic benzoate metabolism in Azoarcus evansii.
AB  - A new principle of aerobic aromatic metabolism has been postulated, which is in
      contrast to the known pathways. In various bacteria the aromatic substrate
      benzoate is first converted to its coenzyme A (CoA) thioester, benzoyl-CoA, which
      is subsequently attacked by an oxygenase, followed by a non-oxygenolytic fission
      of the ring. We provide evidence for this hypothesis and show that benzoyl-CoA
      conversion in the bacterium Azoarcus evansii requires NADPH, O(2) and two protein
      components, BoxA and BoxB. BoxA is a homodimeric 46 kDa iron-sulphur
      flavoprotein, which acts as reductase. In the absence of BoxB, BoxA catalyses the
      benzoyl-CoA stimulated artificial transfer of electrons from NADPH to O(2) via
      free FADH(2) to produce H(2)O(2). Physiologically, BoxA uses NADPH to reduce
      BoxB, a monomeric 55 kDa iron-protein that acts as benzoyl-CoA oxygenase. The
      product of benzoyl-CoA oxidation was identified by NMR spectroscopy as its
      dihydrodiol derivative, 2,3-dihydro-2,3-dihydroxybenzoyl-CoA. This suggests that
      BoxBA act as a benzoyl-CoA dioxygenase/reductase. Unexpectedly, benzoyl-CoA
      transformation by BoxBA was greatly stimulated when another enoyl-CoA
      hydratase/isomerase-like protein, BoxC, was added that catalysed the further
      transformation of the dihydrodiol product formed from benzoyl-CoA. The benzoyl
      CoA oxygenase system has very low similarity to known (di)oxygenase systems and
      is the first member of a new enzyme family.

PMID- 15458419
TI  - Identification and characterization of the Pasteurella multocida toxin
      translocation domain.
AB  - The Pasteurella multocida toxin (PMT) is a potent mitogen which enters the
      cytosol of eukaryotic cells via a low pH membrane translocation event. In common
      with the Escherichia coli cytotoxic necrotizing factor 1 (CNF1), the core of the
      PMT translocation domain is composed of two predicted hydrophobic helices (H1 -
      residues 402-423, H2 - 437-457) linked by a hydrophilic loop (PMT-TL - 424-436).
      The peptide loop contains three acidic residues (D425, D431 and E434), which may
      play a role equivalent to D373, D379 and E382/383 in CNF1. To test this
      hypothesis, a series of point mutants was generated in which acidic residues were
      mutated into the permanently charged positive residue lysine. Individual mutation
      of D425, D431 and E434 each caused a four- to sixfold reduction in toxin
      activity. Interestingly, mutation of D401 located immediately outside the
      predicted helix-loop-helix motif completely abolished toxin activity. Individual
      mutations did not affect cell binding nor greatly altered toxin structure, but
      did prevent translocation of the surface-bound proteins into the cytosol after a
      low pH pulse. Moreover, we demonstrate using an in vitro assay that PMT undergoes
      a pH-dependent membrane insertion.

PMID- 15458420
TI  - YdgT, the Hha paralogue in Escherichia coli, forms heteromeric complexes with H
      NS and StpA.
AB  - In enteric bacteria, proteins of the Hha/YmoA family play a role in the
      regulation of gene expression in response to environmental factors. Interaction
      of both Hha and YmoA with H-NS has been reported, and an Hha/H-NS complex has
      been shown to modulate expression in Escherichia coli of the haemolysin operon of
      plasmid pHly152. In addition to the hns gene, the chromosome of E. coli and other
      enteric bacteria also includes the stpA gene that encodes the StpA protein, an H
      NS paralogue. We report here the identification of the Hha paralogue in E. coli,
      the YdgT protein. As Hha paralogue, YdgT appears to fulfil some of the functions
      reported for StpA as H-NS paralogue: YdgT is overexpressed in hha mutants and can
      compensate, at least partially, some of the hha-induced phenotypes. We also
      demonstrate that YdgT interacts both with H-NS and with StpA. Protein cross
      linking studies showed that YdgT/H-NS heteromeric complexes are generated within
      the bacterial cell. The StpA protein, which is subjected to Lon-mediated
      turnover, was less stable in the absence of Hha or YdgT. Our findings suggest
      that Hha, YdgT and StpA may form complexes in vivo.

PMID- 15458421
TI  - Role of the GGDEF protein family in Salmonella cellulose biosynthesis and biofilm
      formation.
AB  - Salmonella enterica serovar Typhimurium is capable of producing cellulose as the
      main exopolysaccharide compound of the biofilm matrix. It has been shown for
      Gluconacetobacter xylinum that cellulose biosynthesis is allosterically regulated
      by bis-(3',5') cyclic diguanylic acid, whose synthesis/degradation depends on
      diguanylate cyclase/phosphodiesterase enzymatic activities. A protein domain,
      named GGDEF, is present in all diguanylate cyclase/phosphodiesterase enzymes that
      have been studied to date. In this study, we analysed the molecular mechanisms
      responsible for the failure of Salmonella typhimurium strain SL1344 to form
      biofilms under different environmental conditions. Using a complementation assay,
      we were able to identify two genes, which can restore the biofilm defect of
      SL1344 when expressed from the plasmid pBR328. Based on the observation that one
      of the genes, STM1987, contains a GGDEF domain, and the other, mlrA, indirectly
      controls the expression of another GGDEF protein, AdrA, we proceeded on a
      mutational analysis of the additional GG[DE]EF motif containing proteins of S.
      typhimurium. Our results demonstrated that MlrA, and thus AdrA, is required for
      cellulose production and biofilm formation in LB complex medium whereas STM1987
      (GGDEF domain containing protein A, gcpA) is critical for biofilm formation in
      the nutrient-deficient medium, ATM. Insertional inactivation of the other six
      members of the GGDEF family (gcpB-G) showed that only deletion of yciR (gcpE)
      affected cellulose production and biofilm formation. However, when provided on
      plasmid pBR328, most of the members of the GGDEF family showed a strong dominant
      phenotype able to bypass the need for AdrA and GcpA respectively. Altogether,
      these results indicate that most GGDEF proteins of S. typhimurium are
      functionally related, probably by controlling the levels of the same final
      product (cyclic di-GMP), which include among its regulatory targets the cellulose
      production and biofilm formation of S. typhimurium.

PMID- 15458422
TI  - PprA: a novel protein from Deinococcus radiodurans that stimulates DNA ligation.
AB  - The extraordinary radiation resistance of Deinococcus radiodurans results from
      the efficient capacity of the bacterium to repair DNA double-strand breaks. By
      analysing the DNA damage repair-deficient mutant, KH311, a unique radiation
      inducible gene (designated pprA) responsible for loss of radiation resistance was
      identified. Investigations in vitro showed that the gene product of pprA (PprA)
      preferentially bound to double-stranded DNA carrying strand breaks, inhibited
      Escherichia coli exonuclease III activity, and stimulated the DNA end-joining
      reaction catalysed by ATP-dependent and NAD-dependent DNA ligases. These results
      suggest that D. radiodurans has a radiation-induced non-homologous end-joining
      repair mechanism in which PprA plays a critical role.

PMID- 15458424
TI  - The burden of kidney disease: improving global outcomes.
AB  - Chronic kidney disease (CKD) is a worldwide public health problem. There is an
      increasing incidence and prevalence of patients with kidney failure requiring
      replacement therapy, with poor outcomes and high cost. There is an even higher
      prevalence of patients in earlier stages of CKD, with adverse outcomes such as
      kidney failure, cardiovascular disease, and premature death. Patients at earlier
      stages of CKD can be detected through laboratory testing and their treatment is
      effective in slowing the progression to kidney failure and reducing
      cardiovascular events. The science and evidence-based care of these patients are
      universal and independent of their geographic location. There is a clear need to
      develop a uniform and global public health approach to the worldwide epidemic of
      CKD. It is to this end that a new initiative "Kidney Disease: Improving Global
      Outcomes" has been established. Its stated mission is "Improve the care and
      outcomes of kidney disease patients worldwide through promoting coordination,
      collaboration and integration of initiatives to develop and implement clinical
      practice guidelines."

PMID- 15458425
TI  - Vascular calcification: a stiff challenge for the nephrologist: does preventing
      bone disease cause arterial disease?
AB  - There has been an explosion of interest in vascular calcification in the last 5
      years. Four key "germinal" findings have fallen onto very fertile soil. First, on
      the background of an increasing cardiovascular disease burden it has been found
      that at least cross-sectionally, and in a limited fashion prospectively, achieved
      dialysis plasma phosphate levels are linked to all-cause and cardiovascular
      mortality. Second, there are increasing reports of calcific uremic arteriolopathy
      in Australia and the United States. Third, we know know that the mechanical
      properties of the carotid artery, and the aorta, have a profound influence on
      survival for dialysis patients. Vascular calcification itself (as assessed by x
      ray films and ultrasound) has been linked to aortic stiffness. Fourth, increasing
      numbers of studies are showing extremely extensive coronary artery calcification
      (CAC) in dialysis patients, even at a young age. From these apparently unlinked
      observations the following assertion has been posited-that in the widespread
      (over) use of calcium-containing oral phosphate binders (OPB) to prevent uremic
      osteodystrophy in our dialysis population we have unwittingly accelerated
      widespread uremic vasculopathy and thereby contributed to premature
      cardiovascular mortality. It is the purpose of this article to discuss vascular
      calcification (and particularly CAC) in dialysis patients as we understand it
      today. We will review the published series, with special reference to the
      Sevelamer Treat to Goal trial and also discuss the new Kidney Disease Outcome
      Quality Initiative (K-DOQI) guidelines on the use of phosphate binders in chronic
      kidney disease.

PMID- 15458426
TI  - Minireview: functions of the renal tract epithelium in coordinating the innate
      immune response to infection.
AB  - Infection of the urinary tract remains one of the most common infections
      affecting mankind. Renal epithelial cells, being one of the first cells to come
      into contact with invading organisms, are in a key position to coordinate host
      defense. The epithelium not only provides a physical barrier to infection, but
      can also augment the immune response via the production of a number of
      inflammatory mediators and antimicrobial proteins. Recent work has demonstrated
      that cells of the innate immune system, including epithelial cells, express toll
      like receptors (TLRs), with the capacity to recognize bacterial components.
      Although the exact mechanisms remain unclear, engagement of TLRs can lead to
      epithelial cell activation and the production of inflammatory mediators. These
      include complement proteins, other bactericidal peptides, and chemotactic
      cytokines. The resulting inflammatory infiltrate serves to aid bacterial
      clearance, but can also lead to renal damage. In this review, we describe how
      renal epithelial cells contribute to the innate immune response to ascending
      urinary tract infection. We specifically relate previous work to more recent
      developments in this field. An improved understanding of the mechanisms involved
      may highlight potential therapeutic avenues to aid bacterial clearance and
      prevent the renal scarring associated with infection.

PMID- 15458427
TI  - Polyductin, the PKHD1 gene product, comprises isoforms expressed in plasma
      membrane, primary cilium, and cytoplasm.
AB  - BACKGROUND: PKHD1, the autosomal-recessive polycystic kidney disease (ARPKD)
      gene, encodes multiple alternatively spliced transcripts predicted to generate
      membrane-bound and secreted proteins. The longest open reading frame encodes
      polyductin (fibrocystin), a putative 4074 amino acid protein with a single
      transmembrane domain and an intracellular C-terminus. METHODS: To characterize
      the PKHD1 products and their expression profile, we raised polyclonal antibodies
      against different portions of polyductin and analyzed different organs using
      various methods. RESULTS: Western blot analyses demonstrated specific bands of
      >440 kD in human adult kidney, liver, and pancreas and approximately 230 kD in
      kidney and liver, predominantly observed in membrane fractions. The >440-kD
      putative membrane protein was immunoprecipitated from kidney and subsequently
      detected by Western blotting using two distinct antisera. An additional product
      of approximately 140 kD was specifically recognized by affinity-purified antisera
      predominantly in soluble fractions. Immunohistochemistry studies revealed
      specific staining in cortical and medullary collecting ducts and thick ascending
      limbs of Henle (TALH). Serial sections were stained with antibodies against
      aquaporin-2 and Tamm-Horsfall protein to confirm the nephron segment
      localization. Positive staining was also detected in biliary and pancreatic duct
      epithelia. Analyses of mouse developing tissues showed specific staining in the
      ureteric bud branches, intra- and extrahepatic biliary ducts, pancreatic ducts,
      and salivary glands. Immunofluorescence studies in inner medullary collecting
      duct cultured cells and immunoelectron microscopy analysis of medullary
      collecting ducts demonstrated that the protein localizes to the primary cilium.
      Positive signal was also detected in the apical membrane and in cytoplasm.
      CONCLUSION: The results indicate that polyductin is part of the group of
      polycystic kidney disease (PKD)-related proteins expressed in primary apical
      cilia. Our data also suggest that, in addition to its likely involvement in cilia
      function, polyductin probably serves in other subcellular functional roles. The
      detection of three different products using two antisera, with evidence for
      distinct subcellular localizations, suggests that PKHD1 encodes membrane-bound
      and soluble isoforms.

PMID- 15458428
TI  - Fibronectin induces ureteric bud cells branching and cellular cord and tubule
      formation.
AB  - BACKGROUND: The extracellular matrix (ECM) protein fibronectin is involved in
      several stages of embryogenesis. Fibronectin exerts its effect through
      interaction with cellular integrin and nonintegrin receptors. METHODS: We
      investigated the effect of fibronectin on branching and tubulogenesis of ureteric
      bud cells in a three-dimensional gel culture system. Primary ureteric bud cells
      from mouse embryos at gestation 11 days (E11) were isolated and established in
      culture. Fibronectin and integrin subunits were localized using immunoperoxidase
      staining. RESULTS: In three-dimensional collagen type I gel culture of ureteric
      bud cell, fibronectin dose dependently induces cord and tubule formation. Both
      ureteric bud cells and ureteric bud branches in embryonic kidney express the same
      multiple integrin subunits that include beta(1), beta(3), alpha(3), alpha(4) and
      alpha(v). Embryonic kidneys examined at E12, E14, and E16 days of gestation
      express fibronectin in the undifferentiated mesenchyme especially next to
      ureteric bud branches and in the interstitium around glomerulotubular structures
      and blood vessels. Fibronectin expression was similar at the tips and stalks of
      branching ureteric bud. Fibronectin expression is maximum at E12 and decreases
      with advanced gestation. Cultured ureteric bud cells also express fibronectin.
      RGD peptides inhibit cord and tubular formation in the three-dimensional gel.
      Anti-alpha(3)beta(1) antibody partially inhibits fibronectin-induced cord and
      tubule formation. Hepatocyte growth factor (HGF), fibroblast growth factor (FGF),
      and glial cell line-derived neurotrophic factor (GDNF) induce ureteric bud cell
      cord formation in three-dimensional gel. The effects of growth factors are
      delayed and quantitatively less compared to the effect of fibronectin.
      CONCLUSION: Fibronectin induces ureteric bud cells branching and tubulogenesis
      through interaction with multiple integrin receptors. Cultured ureteric bud cells
      express fibronectin and the origin of fibronectin at mesenchyme-ureteric bud
      interface is likely both the metanephric mesenchyme and ureteric bud epithelium.
      Addition of individual neutralizing antibodies to beta(1), beta(3), alpha(3),
      alpha(4,)alpha(6) and alpha(v) integrin subunits does not block the effect of
      fibronectin. Only an antibody to alpha(3)beta(1) integrin substantially blocks
      the effect of fibronectin. Other mechanisms, including unidentified integrins,
      are likely involved in fibronectin-induced cord and tubule formation.

PMID- 15458429
TI  - Liposome-mediated transfer of nitric oxide synthase gene improves renal function
      in ureteral obstruction in rats.
AB  - BACKGROUND: The protective effect of nitric oxide has been demonstrated in
      several renal disease models. We augmented renal nitric oxide production by
      transfer of the inducible nitric oxide synthase (iNOS) gene into rat kidney in
      controls and in unilateral ureteral obstruction (UUO). METHODS: The human iNOS
      gene was inserted into a pcDNA 3.1-backbone plasmid with the FLAG epitope (FLAG
      iNOS). In vitro, transduction of FLAG-iNOS was confirmed by Western blot and
      Griess reaction. In vivo, we transfected either FLAG-iNOS or control plasmid (CMV
      LacZ), using cationic liposomes. Urinary nitric oxide metabolites and
      immunohistochemistry confirmed iNOS transduction. Renal function was also
      assessed. RESULTS: In vitro, increased iNOS expression was demonstrated in human
      embryonic kidney (HEK293) cells, along with increased release of nitric oxide
      metabolites, NO(2)/NO(3). In vivo, FLAG-iNOS was detected by polymerase chain
      reaction (PCR) up to 35 days after the transfection. Urine collection documented
      increased urinary NO(2)/NO(3). Immunohistochemistry localized iNOS to collecting
      ducts, distal tubules, and glomerulus of the injected kidney. Renal function
      measured up to 21 days after transfection in control animals was not
      significantly different between the two groups. In contrast, renal function after
      24 hours of UUO was significantly improved in FLAG-iNOS-treated animals.
      CONCLUSION: This study demonstrates the feasibility of liposome-mediated iNOS
      gene transfer into the kidney. Furthermore, the improvement of renal function in
      UUO demonstrates that the transfected iNOS gene is active and suggests that
      decreased iNOS activity contributes to the decreased renal function in UUO. This
      iNOS construct may have therapeutic utility in the pathophysiologic sequelae of
      UUO and other renal diseases.

PMID- 15458430
TI  - TNF-alpha and IL-1beta-mediated regulation of MMP-9 and TIMP-1 in renal proximal
      tubular cells.
AB  - BACKGROUND: Tubulointerstitial fibrosis is a morphologic hallmark of chronic
      kidney disease and is a key factor in the prediction of progression to end-stage
      renal failure. Disruption of tubular basement membrane and interstitial
      extracellular matrix (ECM) via cytokine-induced alterations in matrix
      metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs)
      may be an important mechanism in this process. The presence of the
      proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin
      1beta (IL-1beta) and their effects on proximal tubular cells may be critical in
      this process. METHODS: Human proximal tubular cells were cultured in hormonally
      defined medium. Cells at 80% confluency were exposed to TNF-alpha (0.1 to 100
      ng/mL) or IL-1beta (0.1 to 100 ng/mL) or a combination of both for 48 hours.
      Activity and expression of MMP-9 was examined by gelatin zymography and Western
      blot analysis. TIMP-1 expression was analyzed by Western blotting. Signaling
      through cytokine receptors, protein kinase C (PKC) and mitogen-activated protein
      kinase (MAPK) pathways was investigated. RESULTS: TNF-alpha but not IL-1beta
      resulted in a dose-dependent increase in the latent form of MMP-9. TIMP-1 was
      decreased by treatment with either TNF-alpha or IL-1beta. Cotreatment with IL
      1beta abolished the induction of MMP-9 but augmented the inhibition of TIMP-1 in
      the presence of TNF-alpha. Inhibition of PKC provided evidence of the importance
      of this pathway in mediating the cytokine-induced suppression of TIMP-1 in human
      kidney (HK-2) cells. Activation of the extracellular signal-regulated protein
      kinase (ERK1/2) MAPK mediated the up-regulation of MMP-9 by TNF-alpha whereas p38
      was found to be involved in the IL-1beta-mediated inhibition of TNF-alpha
      stimulated MMP-9. CONCLUSION: The differential effects of TNF-alpha and IL-1beta
      on proximal tubular MMP-9 and TIMP-1 expression are mediated through the TNF-RI,
      the IL-1-RI and the different signaling pathways of PKC, ERK1/2, and p38 MAPK.
      These findings may provide new insights into the role of proinflammatory
      cytokines TNF-alpha and IL-1beta in the development and possible therapeutic
      intervention in tubulointerstitial fibrosis.

PMID- 15458431
TI  - Urinary excretion of aquaporin-2 water channel exaggerated dependent upon
      vasopressin in congestive heart failure.
AB  - BACKGROUND: Impaired water excretion occurs in patients with congestive heart
      failure. The present study was undertaken to determine whether urinary excretion
      of aquaporin-2 (AQP-2) water channel is exaggerated in patients with congestive
      heart failure dependent upon arginine vasopressin (AVP). METHODS: Sixty-five
      patients with congestive heart failure and eight age- and gender-matched control
      subjects were examined. The patients were divided into four groups according to
      the criteria of New York Heart Association (NYHA). Plasma AVP levels, urinary
      excretion of AQP-2, and cardiac index were determined. RESULTS: Plasma AVP levels
      were progressively increased following the severity of NYHA class in the patients
      with congestive heart failure. Cardiac index was inversely decreased, and there
      was a negative correlation between plasma AVP levels and cardiac index (r=-0.430,
      P < 0.02). Urinary excretion of AQP-2 was 187.3 +/- 50.2 fmol/mg creatinine in
      the control subjects. It was markedly increased in the patients. Urinary
      excretion of AQP-2 was elevated to 1144.4 +/- 257.5 and 990.5 +/- 176.0 fmol/mg
      creatinine in the patients with NYHA class III and class IV, respectively, values
      significantly greater than the control subjects (P < 0.05). Urinary excretion of
      AQP-2 had a positive correlation with plasma AVP levels (r= 0.280, P < 0.02).
      CONCLUSION: The present study indicates that exaggerated urinary excretion of AQP
      2 is dependent on baroreceptor-mediated release of AVP in patients with
      congestive heart failure.

PMID- 15458432
TI  - Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice.
AB  - INTRODUCTION: Reduction of renal mass is frequently associated with progressive
      loss of kidney function. We examined the effects of hyperlipidemia on renal
      pathology and mediators of tissue damage in B6.ROP Os/+ mice, a model of reduced
      renal mass. METHODS: C57BL/6 control mice and B6.ROP Os/+ mice were fed normal
      rodent chow or a high fat, high cholesterol (HFHC) diet for 12 weeks. Kidney
      function and renal pathology were assessed. RESULTS: Hyperlipidemia led to a
      decline in kidney function in C57BL/6 mice. Renal pathology was characterized by
      an increase in glomerular matrix and cellularity, glomerular and
      tubulointerstitial macrophage influx, and increased tubular epithelial cell
      turnover. Chow-fed B6.ROP Os/+ animals demonstrated glomerular hypertrophy with
      an increase in mesangial matrix and cellularity that was characterized by
      macrophage influx and increased proliferation. The tubulointerstitium showed
      increased macrophages as well as tubular atrophy and dilation. Renal pathology
      was accompanied by an increase in blood urea nitrogen (BUN) and proteinuria.
      Hyperlipidemia in B6.ROP Os/+ mice resulted in increased plasma BUN compared to
      chow-fed B6.ROP Os/+ animals and aggravated renal pathology by further increasing
      glomerular matrix and glomerular hypercellularity. Glomerular hypercellularity
      was associated with increased expression of platelet-derived growth factor-B
      (PDGF B) and its receptor beta. Glomerular transforming growth factor-beta (TGF
      beta) mRNA expression was increased in B6.ROP Os/+ mice, hyperlipidemic C57BL/6
      mice and hyperlipidemic B6.ROP Os/+ animals compared to controls and correlated
      with the amount of mesangial matrix. CONCLUSION: This study demonstrates that
      hyperlipidemia worsens renal pathology in B6.ROP Os/+ mice with a decline in
      renal function mediated at least in part through increased renal expression of
      the cytokines PDGF B and TGF-beta.

PMID- 15458433
TI  - Mesangial expression of angiotensin II receptor in IgA nephropathy and its
      regulation by polymeric IgA1.
AB  - BACKGROUND: Enhanced gene expression for the renin-angiotensin system (RAS) is
      detected in glomerular mesangial cells in IgA nephropathy (IgAN). Preliminary
      studies showed a reduced glomerular gene expression of angiotensin II subtype 1
      receptor (AT1R), suggesting a regulatory response to high intrarenal angiotensin
      II (Ang II) concentration in IgAN. METHODS: We examined the effect of polymeric
      IgA1 (pIgA1) from patients with IgAN on the expression of Ang II receptors in
      cultured human mesangial cells (HMC). RESULTS: Polymeric IgA1 from patients with
      IgAN down-regulated the expression of AT1R in HMC in a dose-dependent manner.
      When similar experiments were conducted with addition of an angiotensin
      converting enzyme inhibitor (captopril) or an AT1R antagonist (losartan), there
      was a significant increase in the expression of AT1R. Blockade of Ang II with
      captopril or losartan alone resulted in a stepwise increase of AT1R in cultured
      HMC. Down-regulation of Ang II subtype 2 receptor (AT2R) was not observed in HMC
      cultured with pIgA1 from patients with IgAN. The acute suppressive effect of
      pIgA1 from IgAN on the expression of AT1R was confirmed in HMC incubated with IgA
      isolated from 15 IgAN patients, 15 healthy subjects, and other
      glomerulonephritides control subjects. Reduced glomerular expression of AT1R (but
      not AT2R) was also demonstrated in renal biopsies from patients with IgAN.
      CONCLUSION: Our findings demonstrate an altered AT1R expression in HMC in
      response to raised intrarenal Ang II in IgAN. Our in vitro studies also support
      that an imbalance of AT1R and AT2R activity in HMC following exposure to pIgA
      plays a significant pathogenetic role in the inflammatory injury in IgAN.

PMID- 15458434
TI  - Hyperexpression of the granzyme B inhibitor PI-9 in human renal allografts: a
      potential mechanism for stable renal function in patients with subclinical
      rejection.
AB  - BACKGROUND: Granzyme B-positive T lymphocytes infiltrate renal allografts during
      acute cellular rejection and cause graft injury by inducing apoptosis of tubular
      cells. Protease inhibitor 9 (PI-9), an intracellular serpin that inhibits
      granzyme B, is known to protect cells from the action of cytotoxic T lymphocytes.
      METHODS: Expression of granzyme B and PI-9 in transplant biopsies from patients
      with acute cellular rejection (N= 18), subclinical rejection showing a
      mononuclear cell infiltrate without deterioration of renal function (N= 15), or
      stable transplant function (N= 13) were studied. Immunohistochemical stainings
      were analyzed and scored semiquantitatively by two independent observers who were
      not aware of clinical results. RESULTS: Granzyme B was expressed by mononuclear
      cells in all biopsies with cellular infiltrates. PI-9 was diffusely expressed by
      tubular cells in the allografts of all patients with subclinical rejection. In
      contrast, PI-9 expression was only focally in the patients with clinical
      rejection or without rejection. Although no difference was observed in granzyme B
      levels between acute and subclinical rejection, in subclinical rejection tubular
      epithelial cells showed significantly stronger expression of PI-9 than in acute
      rejection (P= 0.011). CONCLUSION: These data suggest that a high expression of PI
      9 by tubular epithelial cells can serve as one of the factors protecting renal
      allografts from rejection in spite of the presence of inflammatory cell
      infiltrates.

PMID- 15458435
TI  - alpha(v)beta(6) Integrin expression in diseased and transplanted kidneys.
AB  - BACKGROUND: Integrins have been implicated in the pathogenesis of a diverse range
      of kidney diseases. Herein, we provide the first detailed description of an
      epithelial restricted integrin, alpha(v)beta(6), in kidney biopsies from patients
      suffering acute and chronic renal diseases and after transplantation. METHODS:
      Immunoperoxidase staining for beta(6) was performed on 267 selected biopsy
      specimens from native (N= 126) and transplanted kidneys (N= 141) and scored
      semiquantitatively. The site of beta(6) expression in tubules was determined
      using haematoxylin counterstaining and by colocalization with Tamm-Horsfall
      protein. Comparisons were made between subcategories of diseases of native
      kidneys and between "service" and "protocol" biopsies of transplanted kidneys.
      RESULTS: beta(6), when present, is largely confined to the distal tubules and
      collecting ducts, colocated with Tamm-Horsfall protein. When sparsely present, it
      was often restricted to the tubular segment associated with the juxtaglomerular
      apparatus. It was found in tubular cells shed into the urine. beta(6) was not
      expressed in thin membrane nephropathy, or in nonproliferative forms of
      glomerulonephritis, with the exception of focal and segmental glomerulosclerosis
      (FSGS). It was diffusely expressed where there was glomerular necrosis or
      thrombosis and in most forms of acute or chronic tubulointerstitial disease.
      beta(6) was diffusely up-regulated in allografts biopsied for delayed function,
      in almost all kidneys that have clinical or subclinical rejection episodes and
      was prominent in chronic allograft nephropathy. CONCLUSION: beta(6) integrin is
      not normally expressed in adult native or transplanted kidneys but is commonly up
      regulated in the distal tubule in disease. Our descriptive study suggests that it
      is a molecule worthy of further study.

PMID- 15458436
TI  - Selective lymphocyte inhibition by FTY720 slows the progressive course of chronic
      anti-thy 1 glomerulosclerosis.
AB  - BACKGROUND: Progression is a hallmark of chronic renal disease and histologically
      characterized by fibrosis and inflammation of the tubulointerstitial compartment.
      To define the role of lymphocytes in this process, the novel lymphocyte-specific
      inhibitor FTY720 was administered to rats with anti-thy 1-induced chronic
      progressive glomerulosclerosis. In this model, the initial and short-term
      inflammatory glomerular injury progresses self-perpetuatedly toward
      tubulointerstitial fibrosis by not primarily immune-mediated, intrarenal
      mechanisms. METHODS: Chronic progressive glomerulosclerosis was induced by murine
      anti-thy 1 antibody injection into uninephrectomized rats. Treatment with FTY720
      (0.3 mg/kg body weight) was started 7 days after disease induction. Proteinuria
      was measured every 4 weeks. In week 20, the following parameters were determined:
      blood lymphocyte number, kidney function, both glomerular and tubulointerstitial
      histologic matrix accumulation, protein expression of transforming growth factor
      beta1 (TGF-beta1), fibronectin, and plasminogen activator inhibitor-1 (PAI-1) as
      well as infiltration with macrophages and lymphocytes. RESULTS: Treatment with
      FTY720 lowered blood lymphocyte count and renal lymphocyte infiltration highly
      significantly. In comparison to the untreated chronic progressive
      glomerulosclerosis animals, the lymphocyte depletion achieved significantly
      limited the progression of the disease, as shown by lowered proteinuria,
      tubulointerstitial matrix expansion, and TGF-beta1, fibronectin, and PAI-1
      expression, as well as improved renal function. Glomerular matrix protein
      expression and accumulation was moderately lowered by FTY720. Glomerular
      macrophage infiltration was not, tubulointerstitial macrophage infiltration was
      moderately, but not significantly, decreased by FTY720 treatment. CONCLUSION:
      Lymphocyte depletion by FTY720 limits the progression of anti-thy 1-induced
      glomerulosclerosis toward chronic tubulointerstitial fibrosis and renal
      insufficiency. The data suggest that lymphocytes actively participate in the
      progression of chronic experimental kidney disease, and that FTY720 may be a
      novel approach to slow the progressive course of human chronic renal diseases.

PMID- 15458437
TI  - Blockade of the CD154-CD40 costimulatory pathway prevents the development of
      experimental autoimmune glomerulonephritis.
AB  - BACKGROUND: Experimental autoimmune glomerulonephritis (EAG) was induced in
      Wistar-Kyoto (WKY) rats by immunization with rat glomerular basement membrane
      (GBM) in adjuvant. This model is characterized by anti-GBM antibody production,
      accompanied by focal necrotizing glomerulonephritis with crescent formation.
      There is also glomerular infiltration by T cells and macrophages. Our hypothesis
      was that blocking the interaction between CD154 (CD40L) on Th cells and CD40 on
      antigen-presenting cells should inhibit T-cell activation, and thus the
      development of EAG. METHODS: The in vivo effects of a hamster anti-rat monoclonal
      antibody to CD154 (AH.F5) were examined in EAG starting at day -1 prior to
      immunization, day +7 after immunization, or day +14 after immunization. RESULTS:
      When administered from day -1 at a dose of 10 mg/kg intraperitoneally three times
      per week for the duration of the study (4 weeks), AH.F5 resulted in a marked
      reduction in circulating anti-alpha3(IV)NC1 antibodies, deposits of IgG on the
      GBM, albuminuria, deposits of fibrin in the glomeruli, severity of glomerular
      abnormalities, and numbers of glomerular T cells and macrophages. When
      administered from day +7 at the same dose, AH.F5 resulted in a moderate reduction
      in the severity of disease, while administration from day +14 had no significant
      effect. CONCLUSION: These studies demonstrate for the first time that early
      blockade of the CD154-CD40 T-cell costimulatory pathway can prevent the
      development of crescentic nephritis, and that delayed treatment can reduce the
      severity of disease. This confirms the importance of T cell mediated immunity in
      the pathogenesis of EAG, and suggests that strategies targeting T-cell
      costimulation may provide a novel approach in the treatment of human
      glomerulonephritis.

PMID- 15458438
TI  - The amino acid transporter asc-1 is not involved in cystinuria.
AB  - BACKGROUND: The human amino acid transporter asc-1 (SLC7A10) exhibits substrate
      selectivity for small neutral amino acids, including cysteine, is expressed in
      kidney, is located close to the cystinuria B gene and presents sequence variants
      (e.g., E112D) in some cystinuria patients. We have cloned human asc-1, assessed
      its transport characteristics, localized its expression in kidney, searched for
      mutations in cystinuria patients, and tested the transport function of variant
      E112D. METHODS: We used an EST-based homology cloning strategy. Transport
      characteristics of asc-1 were assessed by coexpression with 4F2hc in Xenopus
      oocytes and HeLa cells. Localization of asc-1 mRNA in kidney was assessed by in
      situ hybridization. Exons and intron-exon boundaries were polymerase chain
      reaction (PCR)-amplified from blood cell DNA and mutational screening was
      performed by single-stranded conformational polymorphism (SSCP). RESULTS: Asc-1
      reaches the plasma membrane in HeLa cells, unlike in oocytes, most probably by
      interaction with endogenous 4F2hc and presents similar transport characteristics
      to those in oocytes coexpressing asc-1/4F2hc. Asc-1 mediates a substantial efflux
      of alanine in a facilitated diffusion mode of transport. Expression of asc-1 mRNA
      localized to Henle's loop, distal tubules, and collecting ducts. Finally, SLC7A10
      polymorphisms were identified in cystinuria probands and the SLC7A10 sequence
      variant E112D showed full transport activity. CONCLUSION: The lack of expression
      of asc-1 in the proximal tubule indicates that it plays no role in the bulk of
      renal reabsorption of amino acids. No mutations causing cystinuria have been
      found in SLC7A10. The facilitated diffusion mode of transport and the expression
      in distal nephron suggest a role for asc-1 in osmotic adaptation.

PMID- 15458439
TI  - Uric acid and the state of the intrarenal renin-angiotensin system in humans.
AB  - BACKGROUND: Experimental hyperuricemia is marked by an activated intrarenal renin
      angiotensin system (RAS). The renal vascular response to exogenous angiotensin II
      (Ang II) provides an indirect measure of intrarenal RAS activity. We tested the
      hypothesis that the serum uric acid concentration predicts the renal vascular
      response to Ang II. METHODS: A total of 249 subjects in high sodium balance had
      the renal plasma flow (RPF) response to Ang II measured. Para-aminohippuric acid
      (PAH) clearance was used to estimate RPF. Multivariable regression analysis
      determined if the serum uric acid concentration independently predicts the RPF
      response to Ang II. Variables considered included age, gender, race, body mass
      index (BMI), hypertension status, blood pressure, basal RPF, creatinine
      clearance, serum insulin, serum glucose, serum high-density lipoprotein (HDL),
      serum triglycerides, and plasma renin activity (PRA). RESULTS: Uric acid
      concentration negatively correlated with the RPF response to Ang II (r=-0.37, P <
      0.001). In univariate analysis, age, BMI, hypertension, triglycerides, and blood
      pressure were negatively associated, and basal RPF, HDL, and female gender were
      positively associated with the RPF response to Ang II. In multivariable analysis,
      serum uric acid concentration independently predicted the RPF response to Ang II
      (beta=-5.3, P < 0.001). CONCLUSION: Serum uric acid independently predicted
      blunted renal vascular responsiveness to Ang II, consistent with results from
      experimental hyperuricemia showing an activated intrarenal RAS. This could be due
      to a direct effect of uric acid or reflect a more fundamental renal process.
      These data may have relevance to the association of uric acid with risk for
      hypertension and nephropathy.

PMID- 15458440
TI  - Regulation of vascular permeability factor/vascular endothelial growth factor
      (VPF/VEGF-A) expression in podocytes.
AB  - BACKGROUND: Vascular permeability factor/vascular endothelial growth factor
      (VPF/VEGF-A) is expressed constitutively in the adult glomerular podocytes at
      high levels; however, the regulation of its production is unclear. Recent data
      from podocyte-specific knockout mice suggest that VPF/VEGF-A is critical for the
      proper maintenance of glomerular filtration barrier and the glomerular
      endothelial fenestrae. We hypothesized that the glomerular basement membrane
      (GBM) matrix-podocyte interaction may play a role in the constitutive expression
      of VPF/VEGF-A in the adult glomerulus. METHODS: VPF/VEGF-A mRNA levels in a human
      podocyte cell line grown in the presence of various extracellular matrices were
      quantitated by real-time polymerase chain reaction (PCR) experiments. VPF/VEGF-A
      protein levels in the culture supernatant from the same conditions were measured
      by enzyme-linked immunosorbent assay (ELISA). Promoter activity of VPF/VEGF-A
      gene in these cells was performed by transfecting full length (2.6 kb) VPF/VEGF-A
      promoter, which is fused with luciferase reporter gene. Immunoprecipitation and
      Western blot experiments were carried out in order to detect the association of
      hypoxia-inducible factor-alpha (HIF-alpha) and p300 in podocyte cells. RESULTS:
      In this study, we provide preliminary evidence that signaling through the
      extracellular matrix proteins and, in particular, laminin and its receptor
      alpha(3)beta(1) integrin may regulate VPF/VEGF-A production in cultured podocytes
      in vitro. We also present data that increased activity of the transcription
      factor HIF-alphas in podocyte is not related to hypoxia and may lead to up
      regulation of VPF/VEGF-A transcription. The classical type protein kinase C (PKC)
      may be a potential intermediate signaling molecule in this event. CONCLUSION:
      These data suggest a novel nonhypoxic regulation of VPF/VEGF-A production in the
      glomerulus of the kidney during physiologic states. These observations may form
      the basis of more elaborate studies that will finally provide the detailed
      signaling pathway for VPF/VEGF-A synthesis in podocytes and will help our
      understanding of the pathogenesis of various VPF/VEGF-A-related diseases in the
      glomerulus of the kidney.

PMID- 15458441
TI  - Role of macula densa adenosine triphosphate (ATP) in tubuloglomerular feedback.
AB  - BACKGROUND: Recent studies have shown that adenosine triphosphate (ATP) is
      liberated from macula densa cells in response to increased tubular NaCl in vitro.
      We tested the hypothesis that increased NaCl in the macula densa stimulates the
      release of ATP, resulting in extracellular formation of adenosine which is
      involved in signal transmission of the tubuloglomerular feedback response.
      METHODS: Rabbit afferent arterioles and attached macula densas were
      simultaneously microperfused in vitro. Tubuloglomerular feedback was induced by
      increasing macula densa Na/Cl from 11/10 to 81/80 mmol/L and was measured before
      and after treatment. RESULTS: We first tested whether hydrolysis of ATP is
      required for tubuloglomerular feedback. When we enhanced conversion of ATP to
      adenosine by adding hexokinase or apyrase to the bath and arteriole lumen, the
      tubuloglomerular feedback response was augmented. During the control period,
      tubuloglomerular feedback decreased arteriole diameter by 2.2 +/- 0.2 microm. In
      the presence of hexokinase, tubuloglomerular feedback decreased diameter by 3.4
      +/- 0.3 microm (N= 8) (P < 0.05, with vs. without hexokinase). In the apyrase
      group, tubuloglomerular feedback decreased diameter by 2.7 +/- 0.4 microm during
      the control period. When apyrase was added, tubuloglomerular feedback decreased
      diameter by 4.7 +/- 0.4 microm (N= 8) (P < 0.05, with vs. without apyrase). When
      hydrolysis of adenosine monophosphate (AMP) to adenosine was blocked by
      supplementing the bath with 100 micromol/L alpha,beta-methylene adenosine 5'
      diphosphate (MADP), an inhibitor of 5'-nucleotidase, tubuloglomerular feedback
      response was blocked and diameter remained unchanged. We next studied whether ATP
      released from the macula densa binds to P(2) receptors and activates the
      tubuloglomerular feedback response. The P(2) purinergic receptor inhibitor
      suramin was added to both arteriole lumen and bath. During the control period,
      tubuloglomerular feedback decreased diameter by 3.7 +/- 0.5 microm. Suramin (100
      micromol/L) did not significantly inhibit tubuloglomerular feedback, since in the
      presence of suramin diameter decreased by 3.8 +/- 0.3 microm (N= 7). Finally, we
      added the adenosine A(1) receptor inhibitor FK838 to both bath and lumen and
      found that it completely blocked high NaCl-induced tubuloglomerular feedback.
      CONCLUSION: We concluded that ATP released from the macula densa is broken down
      to form AMP in the extracellular space. AMP in turn is degraded by ecto-5'
      nucleotidases to adenosine, which mediates signal transmission of the
      tubuloglomerular feedback response.

PMID- 15458442
TI  - Aortic pulse wave velocity in renal transplant patients.
AB  - BACKGROUND: In subjects with end-stage renal disease (ESRD) undergoing
      hemodialysis, aortic pulse wave velocity (PWV) is increased independently of
      blood pressure level and mostly is a strong predictor of cardiovascular risk. Few
      studies on this subject have been performed in renal transplant patients.
      METHODS: Aortic PWV was determined noninvasively in 106 patients with kidney
      transplantation and treated using a standard immunosuppression protocol. Mean age
      was 43 +/- 14 years. During the follow-up period (mean duration 54.3 +/- 28.9
      months), the following parameters were studied: characteristics of the renal
      graft, degree of renal insufficiency, number of acute rejections, cardiovascular
      risk factors, drug medications, and cardiovascular complications. RESULTS: Aortic
      PWV was increased in subjects with renal transplants independently of age and
      mean blood pressure. Acute renal rejection and smoking habits were the principal
      factors modulating together: the increase of aortic PWV and the reduction of the
      glomerular filtration rate (GFR). The latter renal parameter was also influenced
      by the donor age. Two main parameters were predictors of cardiovascular events: a
      past history of cardiovascular disease and the pulse pressure x heart rate
      product, the major mechanical consequence of increased PWV. CONCLUSION: In renal
      transplant subjects, tobacco consumption and mostly acute renal rejection
      modulate both aortic stiffness and chronic renal failure independent of blood
      pressure level and donor characteristics. Pulsatile stress mediates
      cardiovascular complications and predicts cardiovascular risk, particularly in
      the presence of increased heart rate.

PMID- 15458443
TI  - Spironolactone prevents early renal injury in streptozotocin-induced diabetic
      rats.
AB  - BACKGROUND: Glomerular and tubulointerstitial injury leads to chronic impairment
      of renal function, and thus, reversal of the injury may improve renal function
      and survival. The present study investigated whether and how mineralocorticoid
      receptor antagonist spironolactone ameliorates early renal injury in
      streptozotocin-induced diabetic rats. METHODS: Streptozotocin (65 mg/kg, single
      intraperitoneal injection)- or vehicle-administered rats were used as diabetic or
      control rats, respectively. The streptozotocin-administered rats were treated
      with spironolactone (50 mg/kg/day sc) for 3 weeks. Among the 3 groups of rats, we
      compared renal fibrosis and renal hypertrophy, using picro-sirius red staining
      and immunohistochemistry of ED-1 macrophage marker, plasminogen activator
      inhibitor-1 (PAI-1), and transforming growth factor (TGF)-beta1. RESULTS: Three
      weeks after administration of streptozotocin, rats exhibited increased collagen
      deposition in glomerular, tubulointerstitial, and perivascular areas in the
      kidney, which was completely attenuated by spironolactone treatment. In rats
      given streptozotocin alone, there were increases in ED-1-positive cell, PAI-1
      expression, and TGF-beta1 expression in glomeruli and tubulointerstitiums, which
      were also suppressed by spironolactone treatment. Maximal glomerular and proximal
      tubular areas were not significantly different among the 3 groups. Rats given
      streptozotocin alone revealed an increase in proximal tubule wall-to-lumen ratio
      that was not influenced by treatment with spironolactone. CONCLUSION:
      Streptozotocin-induced renal fibrosis, PAI-1 expression, TGF-beta1 expression,
      and macrophage infiltration occur via mineralocorticoid receptor, and
      spironolactone ameliorates renal fibrosis presumably via the inhibition of
      macrophage infiltration, PAI-1 expression, and TGF-beta1 expression in
      streptozotocin-induced early diabetic injury.

PMID- 15458444
TI  - HMG-CoA reductase, cholesterol 7alpha-hydroxylase, LDL receptor, SR-B1, and ACAT
      in diet-induced syndrome X.
AB  - BACKGROUND: Long-term consumption of Western diets can lead to acquired syndrome
      X, which presents with obesity, insulin resistance, hypertension, hyperlipidemia,
      and risk of atherosclerotic cardiovascular disease. While plasma lipid
      abnormalities in syndrome X have been well characterized, their molecular basis
      remains unclear. This study explored potential mechanisms of hypercholesterolemia
      in diet-induced syndrome X. METHODS: Female Fischer rats were fed a high-fat,
      refined-carbohydrate (sucrose) diet (HFS) or standard rat chow (low-fat, complex
      carbohydrate, LFCC) for 20 months. Plasma lipids and hepatic tissue mRNA,
      protein, and/or activities of the key enzymes and receptors involved in
      cholesterol metabolism were determined. RESULTS: The HFS group exhibited
      hypertension, hyperlipidemia, insulin resistance, obesity, significant down
      regulation of hepatic cholesterol 7alpha-hydroxylase (the rate-limiting step in
      cholesterol catabolism) and low-density lipoprotein (LDL) receptor (LDL-R, the
      primary pathway of LDL clearance). In contrast, hepatic tissue acyl-coenzyme
      A:cholesterol acyltransferase (ACAT-2, the primary enzyme involved in
      intracellular esterification of cholesterol) and scavenger-receptor class B, type
      1 (SR-B1 or HDL receptor) were up-regulated. While 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase mRNA expression was increased, its protein
      abundance and activity were unchanged, and HMG-CoA reductase-to-cholesterol
      7alpha-hydroxylase ratio was increased in HFS-fed animals. CONCLUSION:
      Hypercholesterolemia in diet-induced syndrome X is associated with depressed
      cholesterol 7alpha-hydroxylase, diminished LDL-R, elevated ACAT, and increased
      HMG-CoA reductase-to-cholesterol 7alpha-hydroxylase ratio. These findings point
      to impaired hepatic catabolism and uptake of cholesterol and inappropriate
      cholesterol production capacity as the underlying causes of hypercholesterolemia
      in rats with diet-induced syndrome X.

PMID- 15458445
TI  - Static intra-access pressure ratio does not correlate with access blood flow.
AB  - BACKGROUND: Access flow (Qa) measurement is recommended by Kidney Disease
      Outcomes Quality Initiative (K/DOQI) as the preferred method for access
      surveillance. Static intra-access pressure ratio (SIAPR) measurement is the
      second surveillance method of choice. The purpose of this prospective multicenter
      study was to investigate the relationship between SIAPR and Qa and to examine the
      premise upon which SIAPR surveillance is based-namely, that high SIAPR is a
      surrogate for low Qa associated with hemodynamically significant stenosis.
      METHODS: SIAPR and Qa (HD01; Transonic Systems, Inc., Ithaca, NY, USA) were
      simultaneously measured monthly in 242 patients [146 prosthetic arteriovenous
      bridge grafts (AVG), 96 autogenous arteriovenous fistulas (AVF)] from three
      centers. SIAPR was measured according to the K/DOQI protocol. RESULTS: There was
      no correlation between Qa and venous or arterial SIAPR in AVGs (R(2)= 0.0037 and
      R(2)= 0.006, respectively, N= 730), or in AVFs (R(2)= 0.0247 and R(2)= 0.0329,
      respectively, N= 431). Of the high SIAPR measurements in AVGs, 81% and 50% were
      associated with Qa > or =600 and Qa > or =1000 mL/min, respectively. Of the AVGs
      studied, 41% (60/146) had consistently high Qa > or =1000 mL/min. Seventy percent
      (42/60) of these high-Qa AVGs had at least two consecutive sessions with high
      SIAPR measurements, thereby meeting the K/DOQI SIAPR criteria for referral. In
      addition, 78% (14/18) of new AVGs with Qa > or =1000 mL/min, and 86% (6/7) of
      AVGs with the highest Qa (> or =2000 mL/min), had high SIAPR. As a result, these
      high-Qa AVGs, which represented the best functioning AVGs by K/DOQI Qa standards,
      were erroneously targeted for referral based on SIAPR measurements. CONCLUSION:
      SIAPR does not correlate with Qa or discriminate between high and low Qa.
      Therefore, because the utility of SIAPR surveillance for detection of clinically
      significant stenosis depends on a correlation with Qa, the current use of
      absolute K/DOQI SIAPR thresholds for intervention based on the presumption that
      such thresholds are indicative of low Qa is not justified, and should be
      discontinued. Studies need to be done to examine the utility of SIAPR for trend
      analysis.

PMID- 15458446
TI  - A genome scan for diabetic nephropathy in African Americans.
AB  - BACKGROUND: There is substantial evidence for a genetic contribution to diabetic
      nephropathy susceptibility in the African American population, but little is
      known about location or identity of susceptibility genes. METHODS: DNA samples
      were collected from 206 type 2 diabetes (T2DM) and end-stage renal disease
      (ESRD)/nephropathy-affected sib pairs from 166 African American families (355
      affected individuals). A genome scan was performed and data analyzed using
      nonparametric linkage regression (NPLR) analysis and ordered subsets analysis
      (OSA) methods. RESULTS: In initial NPLR analyses no logarithm of odds (LOD)
      scores >2.0 were observed. Four loci had LOD scores > or =1.0, with LOD = 1.43 at
      29 cM on chromosome 7p the highest. NPLR analyses of multilocus interactions
      detected 6 loci (7p, 12p, 14q, 16p, 18q, and 21q) with LOD scores 1.15 to 1.63.
      NPLR analyses evaluating phenotypic interactions revealed multiple locations with
      evidence (P < 0.05) for interactions with age-at-onset of ESRD (9 loci), duration
      of diabetes before onset of ESRD (19 loci), and age-at-onset of diabetes (14
      loci). Several loci identified by NPLR analyses were also identified using OSA.
      OSA revealed evidence for a nephropathy locus at 135 cM on chromosome 3 in an
      estimated 29% of the families (LOD = 4.55 in the optimal subset). Additional
      linkage evidence, LOD = 3.59, was observed on chromosome 7p (37% of the families,
      longer duration of diabetes prior to diagnosis of ESRD), and 18q (max. LOD =
      3.72; 64% of the families, early diabetes diagnosis). The 7p linkage has been
      observed in a recent genome scan of African American type 2 diabetes. CONCLUSION:
      This first genome scan of diabetic nephropathy in African Americans reveals
      evidence for susceptibility loci on chromosomes 3q, 7p, and 18q. The 7p locus may
      represent a type 2 diabetes susceptibility locus.

PMID- 15458447
TI  - Impact of hemodialysis on endogenous plasma and muscle carnitine levels in
      patients with end-stage renal disease.
AB  - BACKGROUND: End-stage renal disease (ESRD) patients undergoing hemodialysis
      treatment have reduced plasma L-carnitine levels; however, the relationship
      between dialysis age and carnitine status is poorly understood. This study
      examined the relationship between duration of dialysis and plasma and skeletal
      muscle concentrations of L-carnitine and its esters in ESRD patients. METHODS:
      Blood samples were collected from 21 patients at baseline and throughout the
      first 12 months of hemodialysis. In 5 patients, muscle samples were obtained
      after 0, 6, and 12 months of hemodialysis. Blood and muscle samples were
      collected from an additional 20 patients with a mean dialysis age of 5.10 years.
      L-carnitine, acetyl-L-carnitine, and total L-carnitine were measured by high
      performance liquid chromatography (HPLC). RESULTS: The mean +/- SD plasma L
      carnitine concentration in ESRD patients who had not yet started hemodialysis was
      50.6 +/- 20.0 micromol/L. Significantly lower concentrations were observed after
      12 months (29.7 +/- 10.5 micromol/L) and >12 months (22.0 +/- 5.4 micromol/L) of
      hemodialysis treatment. Acetyl-L-carnitine also declined with dialysis age, while
      plasma nonacetylated acylcarnitines continued to increase with the progression of
      hemodialysis therapy. An inverse relationship between dialysis age and muscle L
      carnitine concentrations was observed. CONCLUSION: Long-term hemodialysis
      treatment is associated with a significant reduction in endogenous plasma and
      muscle L-carnitine levels and a significant increase in plasma acylcarnitines.
      The majority of the change in plasma L-carnitine concentrations occurs within the
      first few months of hemodialysis, while muscle levels continue to decline after
      12 months of treatment.

PMID- 15458448
TI  - Clinical features and outcome of patients with both ANCA and anti-GBM antibodies.
AB  - BACKGROUND: Patients have been described who have both anti-neutrophil cytoplasm
      antibodies (ANCA) and anti-glomerular basement membrane (GBM) antibodies. We have
      attempted to define the true prevalence of such "double positive" patients, and
      describe in detail their clinical features and outcome. METHODS: We have reviewed
      all serologic assays performed between 1990 and 2000 in a single institution, and
      the case notes of patients having sera positive for both ANCA and anti-GBM
      antibodies. During this time 20,392 sera were initially tested for ANCA, and 4808
      sera tested for anti-GBM antibodies. RESULTS: Five percent of all ANCA-positive
      serum samples were also positive for anti-GBM antibodies, and 32% of all anti-GBM
      positive samples had detectable ANCA. Of 27 patients with both antibodies, 82%
      had anti-myeloperoxidase specific P-ANCA. Pulmonary hemorrhage occurred in 44%.
      Renal biopsy showed extensive glomerular cellular crescents in most patients.
      Patient and renal survival rates were 52% and 26%, respectively, at one year.
      Sixty-eight percent of patients were dialysis-dependent at presentation, and none
      of these recovered renal function, despite immunosuppression with or without
      plasma exchange. CONCLUSION: Serologic evidence of double positivity for both
      ANCA and anti-GBM antibodies is common in patients with either antibody. In our
      study these patients have a poor prognosis when presenting with severe disease
      and initially behave more like anti-GBM disease than vasculitis. Recovery from
      severe renal failure is rare.

PMID- 15458449
TI  - Pediatric acute renal failure in southwestern Nigeria.
AB  - BACKGROUND: Acute renal failure (ARF) was investigated to determine the
      prevalence of ARF clinical types, etiology, comorbidities, and outcome in
      Nigerian children. METHODS: Consecutive cases of ARF admitted from March, 1994
      through February, 2003 were prospectively studied. Information were obtained
      concerning the following: age, gender, body surface area, early (within 48 hours
      of onset of ARF) or late (>48 hours of onset of ARF) presentation, admission
      duration, etiology, comorbidities, urine volume/day, dialysis need, reasons for
      considering dialysis, laboratory investigations, and outcome in each patient.
      Histopathologic reports of percutaneous renal and surgical biopsies, as well as
      autopsy specimens, were reviewed. RESULTS: There were 78 boys and 45 girls (M:F,
      1.73:1); mean age was 6.28 +/- 4.0 years. A portion of patients presented early
      (46.3%), while 53.7% presented late. Oliguric (63.41%), anuric (20.33%), and
      nonoliguric (16.26%) ARF were the clinical types seen. Dialysis requirement was
      significantly higher in oliguric (P < 0.005) and anuric (P < 0.005) than
      nonoliguric ARF. Primary and secondary etiologies accounted for 29% and 71% of
      ARF cases, respectively. Renal Burkitt's lymphoma (47.2%), glomerulonephritis
      (27.8%), nephrotic syndrome (16.7%), hemolytic uremic syndrome (5.5%), and acute
      tubulointerstitial nephritis (2.8%) were primary etiologies. Plasmodium
      falciparum malaria (42.53%), septicemia (28.73%), hypovolemia (11.49%), and
      obstructive uropathy (8.05%) were major secondary etiologies. Financial
      constraints on the part of parents of patients, as well as inadequate and/or lack
      of dialysis equipment, were major inhibitions to effective management of the
      patients; in fact, 6 patients took voluntary discharge due to inability to afford
      the cost of treatment. Mortality risk factors were late presentation [odds ratio
      (OR) 3.5, P < 0.001], dialysis eligibility (OR 3.8, P < 0.001), nondialysis (OR
      23.1, P= 0.00004), primary etiology (OR 2.6, P < 0.025), and presence of > or =2
      comorbidities (OR 2.9, P < 0.025); overall mortality rate was 46.2%. CONCLUSION:
      These results show that many of the causes of ARF in our patients are
      preventable; it should be possible to reduce morbidity due to ARF through
      purposive preventive measures.

PMID- 15458450
TI  - Effect of fluvastatin on renal end points in the Assessment of Lescol in Renal
      Transplant (ALERT) trial.
AB  - BACKGROUND: Hyperlipidemia is a risk factor for long-term renal transplant
      dysfunction, but no prospective clinical trials have investigated the effects of
      statin treatment on graft function in renal transplant recipients. The aim of the
      present study was to evaluate the effect of fluvastatin on long-term renal
      transplant function and development of chronic allograft nephropathy in the ALERT
      (Assessment of Lescol in Renal Transplantation) study. METHODS: ALERT was a
      randomized, double-blind, placebo-controlled study of the effect of fluvastatin,
      40 mg and 80 mg daily, in renal transplant recipients. Patients were randomized
      to receive either fluvastatin (N= 1050) or placebo (N= 1052) and followed for
      five to six years. Renal end points included graft loss or doubling of serum
      creatinine or death; glomerular filtration rate (GFR) was also measured during
      follow-up in a subset of patients (N= 439). RESULTS: There were 283 patients
      (13.5%) with graft loss, mainly due to chronic rejection (82%), yielding an
      annual rate of 2.4%. Fluvastatin treatment significantly lowered mean low-density
      lipoprotein (LDL)-cholesterol levels by 32% (95% CI -33 to -30) compared with
      placebo, but had no significant effect on the incidence of renal graft loss or
      doubling of serum creatinine, or decline in GFR throughout follow-up in the whole
      study population. Neither was any treatment effect by fluvastatin found in any of
      the subgroups analyzed. CONCLUSION: Fluvastatin treatment significantly improves
      lipid values in renal transplant recipients but has no effect on graft loss or
      doubling of serum creatinine.

PMID- 15458451
TI  - Cationic charge-preferential IgG reabsorption in the renal proximal tubules.
AB  - BACKGROUND: The brush border of the renal proximal tubules has a polyanionic
      charge. Since immunoglobulin G (IgG) molecules have a wide range of charge
      diversity, reabsorption of urinary IgG molecules are supposed to be influenced by
      the electrostatic interaction. METHODS: Charge diversity of serum and urinary IgG
      molecules in patients with various renal diseases (N= 12) and premature neonates
      (N= 3) were analyzed by isoelectric focusing and Immunoblotting. RESULTS: In
      patients with glomerular diseases, urinary IgG was solely composed of neutral and
      anionic IgG, whereas that of the cationic part (isoelectric point >8) was not
      observed. By contrast, in patients with proximal tubular diseases (Dent's disease
      and idiopathic Fanconi syndrome), the proportion of the cationic IgG was similar
      to that of serum IgG. In addition, the cationic part of IgG in the urine was
      found in the neonates with a gestational age of 28 and 31 weeks, but not found in
      those of 35 weeks. CONCLUSION: The results suggest that renal proximal tubules
      reabsorb the urinary IgG in a cationic preferential way, and this mechanism
      requires renal maturation.

PMID- 15458452
TI  - Pain patterns in patients with polycystic kidney disease.
AB  - BACKGROUND: Pain is a common problem in patients with polycystic kidney disease
      (PKD), but patterns have not been characterized as to frequency and severity.
      Physicians should be aware of pain problems so an approach to chronic pain
      management can be pursued. METHODS: One hundred seventy-one completed
      questionnaires out of 300 distributed to PKD patients whose renal function ranged
      from normal to end-stage renal disease (ESRD) were analyzed. Age at diagnosis of
      PKD was documented, and patients noted how the diagnosis was made. Location,
      severity, and frequency of pain were characterized. The Visual Analogue Scale
      (VAS) was used to measure pain intensity. RESULTS: There were 94 females and 77
      male respondents, with a mean age of 47.4 years. Initial diagnosis of PKD
      occurred at a mean age of 31.6 years. Caucasians comprised 92.2% of the
      respondents. Patients' symptoms, a family history of PKD, and discovery of PKD
      during evaluation for hypertension or hematuria were the most frequent factors
      that led to the diagnosis. Order of frequency of pain was: low back pain,
      abdominal pain, headache, chest pain, and leg pain. Severity of pain, documented
      by the VAS intensity, was 4 to 5/10 in the majority of patients. CONCLUSION:
      Pain, which can be diffuse, is the most frequent symptom that led to the
      diagnosis of PKD in patients who responded to this questionnaire, and occurs with
      greater frequency than generally appreciated. Physicians need to obtain a
      detailed history about pain in their PKD population so as to allow an approach to
      pain management.

PMID- 15458453
TI  - Predictors of bleeding complications in percutaneous ultrasound-guided renal
      biopsy.
AB  - BACKGROUND: The risks associated with performing a percutaneous renal biopsy have
      substantially decreased in the past two decades because of technical advances in
      the method. However, bleeding complications still occur, resulting in increased
      hospital stay and treatment costs. METHODS: We investigated the predictive value
      of demographics (age, gender), clinical data (blood pressure), baseline chemistry
      (hemoglobin/hematocrit, prothrombin time, partial thromboplastin time, bleeding
      time, serum creatinine, daily proteinuria), and needle size for the risk of major
      (need for blood transfusion, nephrectomy, or angiography) or minor (no need for
      any intervention) postrenal biopsy bleeding complications. This was a prospective
      cohort study of 471 patients who underwent ultrasound-guided biopsy of native
      kidney by automated needle in a single center; all biopsies were performed by two
      experienced nephrologists. Patients with transplant kidneys were excluded from
      the study. Predictors of postbiopsy bleeding were assessed by multiple linear and
      multivariate logistic regression analysis. Data are presented as unadjusted (OR)
      and adjusted odds ratios (AOR) with 95% confidence intervals (CI). RESULTS: The
      study cohort consisted of 471 (277 males, 194 females) patients. Of these, 161
      (34.1%) experienced postbiopsy bleeding [157 (33.3%) hematomas, 2 (0.4%) gross
      hematuria, 2 (0.4%) arteriovenous fistula]. Major complications were seen in 6
      (1.2%) patients (blood transfusion, N= 2; angiography, N= 3; nephrectomy, N= 1),
      but no deaths occurred. The risk of postbiopsy bleeding was higher in women
      (39.7% women, 30.3% men, AOR 2.05, 95% CI 1.26 to 3.31, P= 0.004), younger
      subjects (35.0 +/- 14.5 years vs. 40.3 + 15.4, AOR 0.80, CI 0.68 to 0.94, P=
      0.006), and patients with higher baseline partial thromboplastin time (102.7 +
      11.8% vs. 100.1 + 10.0%, AOR 1.26, CI 1.02 to 1.54, P= 0.032). These findings
      were independent of size of hematoma. CONCLUSION: Although the methods for
      performing a percutaneous renal biopsy have improved in the past two decades,
      renal biopsy is still not a risk-free procedure. Of the data routinely collected
      for potential predictors of postbiopsy bleeding complications, only gender, age,
      and baseline partial thromboplastin time show a significant predictive value. The
      other variables investigated do not have any predictive value.

PMID- 15458454
TI  - Initial clinical results of the bioartificial kidney containing human cells in
      ICU patients with acute renal failure.
AB  - BACKGROUND: Acute renal failure (ARF) in intensive care unit patients continues
      to have mortality rates exceeding 70%, despite hemodialysis or continuous renal
      replacement therapy (CRRT). The delivery of cellular metabolic function to CRRT
      may provide more complete renal replacement therapy, thereby changing the natural
      history of this disease process. An FDA-approved Phase I/II clinical trial on 10
      patients has been completed, and demonstrated that this experimental treatment
      can be delivered safely for up to 24 hours. METHODS: The bioartificial kidney is
      a synthetic hemofilter connected in series with a bioreactor cartridge containing
      approximately 10(9) human proximal tubule cells, as a renal tubule assist device
      (RAD), within an extracorporeal perfusion circuit utilizing standard
      hemofiltration pump systems. All 10 patients had ARF and multiorgan failure
      (MOF), with predicted hospital mortality rates averaging above 85%. RESULTS: Data
      indicate that the RAD maintains viability, durability, and functionality in this
      ex vivo clinical setting. The device also demonstrated differentiated metabolic
      and endocrinologic activity, with glutathione degradation and endocrinologic
      conversion of 25-OH-D(3) to 1,25-(OH)(2)-D(3). All but one treated patient with
      more than a 3-day follow-up in the intensive care unit showed improvement as
      assessed by acute physiologic scores 1 to 7 days following therapy. Six of the 10
      treated patients survived past 30 days. One patient expired within 12 hours after
      RAD treatment due to his family's request to withdraw ventilatory life support.
      Three other patients died due to complications from acute or chronic
      comorbidities unrelated to ARF or RAD therapy. Plasma cytokine levels suggest
      that RAD therapy produced dynamic and individualized responses in patients. For
      the subset of patients who had excessive proinflammatory levels, RAD treatment
      resulted in significant declines in granulocyte colony stimulating factor (G
      CSF), interleukin (IL)-6, IL-10, and IL-6/IL-10 ratios. CONCLUSION: The addition
      of human renal tubule cell therapy to CRRT has been accomplished and demonstrates
      metabolic activity with systemic effects in patients with ARF and MOF. These
      initial clinical results are encouraging, so that a randomized, controlled Phase
      II clinical trial is underway to further assess the clinical safety and efficacy
      of this new therapeutic approach.

PMID- 15458455
TI  - Enzyme therapy for Fabry disease: neutralizing antibodies toward agalsidase alpha
      and beta.
AB  - BACKGROUND: Fabry disease is an X-linked inherited disorder that is caused by
      excessive lysosomal globotriaosylceramide (CTH) storage due to a deficiency in
      alpha-galactosidase A (alpha-Gal A). Two recombinant enzyme preparations have
      been approved as treatment modality. We studied emergence and properties of alpha
      Gal A antibodies in treated patients. METHODS: During the first 6 to 12 months of
      intravenous administration of recombinant enzymes (rh-alpha-Gal A) formation of
      antibodies was studied in 18 adult Fabry patients (two females). RESULTS: The
      female patients did not develop detectable amounts of antibodies following enzyme
      therapy. After 6 months of treatment with either agalsidase alpha or beta, 11/16
      male patients showed high titers of immunoglobulin G (IgG) antibodies that cross
      react in vitro similarly with both recombinant enzymes. The anti-rh-alpha-Gal A
      IgG neutralizes rh-alpha-Gal A activity in vitro for 65% to 95%. During infusion
      with rh-alpha-Gal A, circulating enzyme-antibody complexes are formed and these
      complexes are taken up by leukocytes in the peripheral blood. After 6 months of
      treatment all IgG-negative patients showed a significant (P < 0.01) reduction of
      urinary CTH (1890 +/- 797 to 603 +/- 291 nmol CTH/24hr urine), compared to IgG
      positive patients (mean increase from 2535 +/- 988 to 2723 +/- 1212), suggesting
      a negative effect of circulating antibodies on renal tubular CTH clearance.
      CONCLUSION: Emergence of antibodies with in vivo neutralizing capacities is
      frequently encountered in treated Fabry disease patients. Complete cross
      reactivity of these antibodies suggests that it is unlikely that switching from
      one to the other recombinant protein prevents the immune response and related
      effects. Further studies on the clinical implications of alpha-Gal A antibodies
      are essential.

PMID- 15458456
TI  - Progression of nephropathy in type 2 diabetic patients.
AB  - BACKGROUND: Nephropathy in type 2 diabetes is the single most common cause of end
      stage renal disease (ESRD), but the decline in kidney function varies
      considerably between individuals, and determinants of renal function loss, early
      in the course of renal disease, have not been clearly identified. METHODS: In a
      prospective observational study, we followed 227 (60 female) Caucasian type 2
      diabetic patients with nephropathy for 6.5 (range 3 to 17) years from a baseline
      glomerular filtration rate (GFR) of 83 (SD30) mL/min/1.73m(2) with 7 (range 3 to
      22) measurements of GFR ((51)Cr-EDTA) per patient. We evaluated determinants of
      (1) rate of decline in GFR, (2) risk of doubling in serum creatinine or ESRD, and
      (3) mortality using potential risk factors at baseline and during follow-up.
      RESULTS: The mean (SD) rate of decline in GFR was 5.2 (4.1) mL/min/year. In
      multivariate regression analysis, higher baseline albuminuria, systolic blood
      pressure (SBP), hemoglobin A1c, GFR, age, and degree of diabetic retinopathy were
      significantly associated with increased rate of decline in GFR (R(2) (adj) 0.24).
      During follow-up, elevated mean albuminuria, SBP, hemoglobin A1c, and lower
      hemoglobin, heavy smoking, and presence of diabetic retinopathy were
      significantly associated with increased decline in GFR (R(2) (adj) 0.26). During
      follow-up, 63 patients had a doubling in serum creatinine or developed ESRD, and
      79 patients died, primarily due to cardiovascular disease. In Cox regression
      analysis, higher baseline albuminuria, hemoglobin A1c, and SBP, together with
      lower GFR and hemoglobin, were significantly associated with shorter time to
      doubling of serum creatinine or ESRD. Higher baseline albuminuria, hemoglobin
      A1c, SBP, and age were significantly associated with increased mortality.
      CONCLUSION: Our long-term prospective study of type 2 diabetic patients with
      nephropathy has revealed several modifiable risk factors of enhanced progression
      in kidney disease and increased mortality.

PMID- 15458457
TI  - Early prediction of IgA nephropathy progression: proteinuria and AOPP are strong
      prognostic markers.
AB  - BACKGROUND: Inflammation and oxidative stress have been incriminated in the
      pathogenesis of IgA nephropathy (IgAN). The aim of the present study was to
      assess whether markers reflecting these pathophysiologic processes, namely C
      reactive protein (CRP) and advanced oxidation protein products (AOPP), would
      allow-in conjunction with clinical and histopathologic parameters-to predict
      disease progression. METHODS: Between 1994 and 1997, 120 adult patients with
      biopsy-proven IgAN were included in a prospective cohort study, and followed
      until the end of 2002 or start of dialysis. In every patient, we determined
      plasma levels of CRP and AOPP. These parameters were included, together with
      clinical data, in a multivariate Cox proportional hazard regression analysis,
      with halving of baseline creatinine clearance as the primary renal end point.
      RESULTS: A total of 51 patients reached the renal end point, including 30 who had
      to start dialysis. With multivariate analysis, the most potent independent risk
      factors of poor renal outcome were proteinuria > or =1 g/day [proportional hazard
      risk (HR) = 23.7, P= 0.0001], hypertension (HR = 8.13, P= 0.008), and AOPP plasma
      level (HR = 1.09 per 10 micromol/L, P= 0.042), whereas angiotensin II inhibitors
      were protective (HR = 0.19, P= 0.001). CONCLUSION: Our data support the role of
      oxidative stress in the pathogenesis of IgAN and suggest that patients with
      proteinuria > or =1 g/day should be eligible for early implemented antioxidant
      and/or anti-inflammatory therapeutic strategies, with AOPP plasma level as a
      surrogate marker to evaluate their effects.

PMID- 15458458
TI  - Spectrum of acute renal failure in the intensive care unit: the PICARD
      experience.
AB  - BACKGROUND: Acute renal failure (ARF) in the critically ill is associated with
      extremely high mortality rates. Understanding the changing spectrum of ARF will
      be necessary to facilitate quality improvement efforts and to design successful
      interventional trials. METHODS: We conducted an observational cohort study of 618
      patients with ARF in intensive care units at five academic medical centers in the
      United States. Participants were required to sign (or have a proxy sign) informed
      consent for data collection. A comprehensive data collection instrument captured
      more than 800 variables, most on a daily basis, throughout the course of ARF.
      Patient characteristics, dialysis status, and major outcomes were determined and
      stratified by clinical site. RESULTS: The mean age was 59.5 years, 41% were
      women, and 20% were of minority race or ethnicity. There was extensive
      comorbidity; 30% had chronic kidney disease, 37% had coronary artery disease, 29%
      had diabetes mellitus, and 21% had chronic liver disease. Acute renal failure was
      accompanied by extrarenal organ system failure in most patients, even those who
      did not require dialysis. Three hundred and ninety-eight (64%) patients required
      dialysis. The in-hospital mortality rate was 37%, and the rate of mortality or
      nonrecovery of renal function was 50%. The median hospital length of stay was 25
      days (26 days, excluding patients who died). CONCLUSION: There is a changing
      spectrum of ARF in the critically ill, characterized by a large burden of
      comorbid disease and extensive extrarenal complications, obligating the need for
      dialysis in the majority of patients. There is wide variation across institutions
      in patient characteristics and practice patterns. These differences highlight the
      need for additional multicenter observational and interventional studies in ARF.

PMID- 15458459
TI  - Effectiveness and safety of dialysis vascular access procedures performed by
      interventional nephrologists.
AB  - BACKGROUND: The purpose of this report was to analyze the results obtained from a
      group of interventional nephrologists working in multiple centers performing
      basic procedures that are used routinely in the management of vascular access
      problems, with an effort toward establishing standards for evaluating success,
      complication rates, and acceptable times for procedure duration and fluoroscopy.
      METHODS: Data on six basic procedures were analyzed-angioplasty of arteriovenous
      fistulas (AVF-PTA), angioplasty of synthetic grafts (graft-PTA), thrombectomy of
      arteriovenous fistulas (AVF declot), thrombectomy of synthetic grafts (graft
      declot), placement of tunneled dialysis catheters (TDC placement), and tunneled
      dialysis catheter exchange (TDC exchange). These data were examined both as a
      group and by individual physician operator. RESULTS. A total of 14,067 cases were
      performed under the six categories of procedure that were the subject of this
      report; 13,503 cases (96.18%) were successful. The overall complication rate for
      the combined group of procedures was 3.54%, with 3.26% falling within the minor
      category and 0.28% within the major. The number of cases performed in each
      individual category with success rates for each were as follows: TDC placement
      1765 cases, 98.24% successful; TDC exchange-2262 cases, 98.36% successful, AVF
      PTA-1561 cases, 96.58% successful; graft-PTA-3560 cases, 98.06% successful; AVF
      declot-228 cases, 78.10% successful; graft declot-4671 cases, 93.08% successful.
      CONCLUSION: This study demonstrates that appropriately trained interventional
      nephrologists can perform these basic procedures in both a safe and effective
      manner.

PMID- 15458460
TI  - Prognostic value of inducible myocardial ischemia in predicting cardiovascular
      events after renal transplantation.
AB  - BACKGROUND: The aims of the present study were to determine the prevalence of
      inducible myocardial ischemia (IMI) in renal transplant recipients (RTR) more
      than 50 years old, to identify predictors of IMI, and to search for its
      prognostic value. METHODS: Among the 377 renal transplantations performed between
      1989 and 1998 in a single institution, 120 were done in patients > or =50 years
      old, and 97 were recruited for the study. During the last quarter of 1998, all of
      them underwent an exercise test (EST), an exercise-thallium 201 single photon
      emission computed tomography coupled with dipyridamole (SPECT), and 81% of them
      had a dobutamine stress echocardiography (DSE). Patients with IMI subsequently
      underwent coronary angiography to detect coronary stenosis. RESULTS: IMI was
      present in 12 of the 97 patients (10%). The diagnosis was evidenced by EST in
      four cases, by SPECT in 11 cases, and DSE in three cases. Five of these 12
      patients (42%) had significant coronary artery stenosis (> or =50%). Multivariate
      analysis of several pre- and post-transplant variables evidenced acute rejection
      and left ventricular hypertrophy as significant correlates of IMI (both P <
      0.03). Patients were prospectively followed-up for 48 months for the occurrence
      of major cardiovascular events. Kaplan-Meier analysis revealed a significant
      increase in cardiovascular events in the IMI group (P < 0.0001). In addition, the
      Cox proportional hazards model revealed that IMI and diabetes mellitus had an
      independent significant effect on the occurrence of major cardiovascular events.
      CONCLUSION: IMI was present in 10% of RTR aged > or =50 years, and was predicted
      by acute rejection and left ventricular hypertrophy. IMI had a strong effect on
      major cardiovascular events in this population.

PMID- 15458461
TI  - Kinetic study of adenosine concentrations and the expression of adenosine
      deaminase in mononuclear cells during hemodialysis.
AB  - BACKGROUND: We previously showed that high intralymphocytic adenosine (Ado)
      concentrations are found in hemodialyzed patients due to the reduced activity of
      mononuclear cell adenosine deaminase (MCADA). These abnormalities contribute to
      the immune defect observed in HD patients. The kinetics of these abnormalities
      and the causes of the low MCADA activity, however, have not been investigated.
      Here, we addressed this question. Since interferon gamma (IFNgamma) partially
      modulates MCADA, we also evaluated the effect of IFNgamma on MCADA activity in
      vitro. METHODS AND RESULTS: The study included 12 patients (eight men and four
      women) who were observed from the first to the 36th hemodialysis (HD) session,
      and eight healthy subjects (controls). MCADA activity and Ado concentrations were
      normal before the first HD session. Ado concentrations progressively increased
      from the first (10.5 +/- 3.1 pmol/10(7) cells) to the fourth session (26.7 +/- 3
      pmol/10(7) cells), before stabilizing at a high level. MCADA activity increased
      transiently until the second session (2.2 +/- 0.5 IU/10(7) cells before HD vs.
      2.8 +/- 0.6 IU/10(7)cells), and then decreased and stabilized at a low level (1.0
      +/- 0.5 IU/10(7)cells). The amount of MCADA mRNA transiently increased until the
      third session (mRNA MCADA/mRNA beta-actin: 0.6 +/- 0.2 vs. 0.8 +/- 0.2), and then
      decreased to 0.3 +/- 0.1 at the 36th session. MCADA activity underwent a dose
      dependent increase after IFNgamma stimulation. CONCLUSION: HD affects the
      transcription of the gene encoding MCADA after just three HD sessions, leading to
      decreased MCADA activity and increased plasma concentration of Ado.

PMID- 15458462
TI  - Effect of spironolactone on K(+) homeostasis and ENaC expression in lymphocytes
      from chronic hemodialysis patients.
AB  - BACKGROUND: Cardiac disease is the major cause of death in hemodialysis patients
      (HD). It is now clear that aldosterone has deleterious effects in the
      cardiovascular system. In the present study, we evaluated the effects of an
      aldosterone-antagonist, spironolactone, on the extrarenal regulation of potassium
      in HD patients. Furthermore, to validate the effectiveness of the spironolactone
      dose-design, we measured the expression of Na(+)-channel (ENaC alpha subunit) in
      peripheral blood mononuclear cells (PBMC), before and after a two-week course of
      spironolactone. METHODS: The study design included a two-week baseline period,
      followed by spironolactone treatment (50 mg three times weekly for 15 days), and
      by a two-week washout period and then a two-week placebo period. An oral K(+)
      load (0.3 mEq/K(+) kg body weight plus carbohydrates) was administered at the end
      of each period, and time-course of plasma potassium was evaluated. ENaC
      expression in PBMC was assessed before and after spironolactone. RESULTS: The
      maximal increase in plasma potassium after the K(+) carbohydrate load was:
      control 5.33 +/- 0.88 mEq K(+)/L; spironolactone 5.23 +/- 0.68 mEq K(+)/L;
      placebo 5.38 +/- 0.61 mEq K(+)/L (N= 9). No patients developed hyperkalemia
      during the spironolactone treatment period. ENaC expression was significantly
      higher in all six HD patients studied, compared to control subjects (P < 0.05).
      Treatment with spironolactone in HD patients reduced alpha subunit mRNA
      expression to values similar to those of normal subjects. CONCLUSION:
      Spironolactone may be considered for the treatment of selected chronic HD
      patients. The effect of the drug on a known target of aldosterone, the ENaC,
      demonstrates the effectiveness of the drug to block aldosterone effects in
      nonepithelial tissues.

PMID- 15458463
TI  - Patient and graft outcomes from older living kidney donors are similar to those
      from younger donors despite lower GFR.
AB  - BACKGROUND: Donor age adversely affects deceased-donor kidney transplant
      outcomes, but its influence on living-donor transplantation is less well
      characterized. METHODS: Living-donor kidney transplants at a single center
      between 1998 and 2000 were reviewed. Data were abstracted for 52 transplants from
      donors aged > or =50 years and for a matched group of 104 transplants from donors
      aged <50 years. Survival indices were compared during the first three years' post
      transplantation. Functional indices, including serial iothalamate clearances,
      were compared at 1, 12, and 24 months. RESULTS: Predonation glomerular filtration
      rate (GFR) was lower among older donors (94 +/- 12 vs. 108 +/- 17 mL/min/SA) but
      post-transplant compensatory hypertrophy was similar (11.7 +/- 26.3% vs. 7.7 +/-
      31.4%). Recipients of older-donor grafts were older (52.8 +/- 16.5 vs. 46.1 +/-
      15.1 years) and more frequently unrelated to the donor (54% vs. 39%). Trends
      toward higher frequency of slow graft function, cytomegalovirus (CMV) infection,
      and polyomavirus nephropathy were observed for older-donor grafts. Three-year
      recipient, graft, and death-censored graft survivals were > or =90% for both
      groups. At 1, 12, and 24 months, serum creatinine was higher and GFR was lower
      among recipients of older- compared with younger-donor grafts. Other functional
      indices (urine total protein, serum potassium and uric acid, hemoglobin, and
      number of antihypertensives) were not different. Donor age correlated with graft
      GFR at 1, 12, and 24 months for the entire study cohort by linear regression.
      CONCLUSION: Older donor age does not preclude excellent results from living-donor
      kidney transplantation but should be appreciated as being associated with
      relatively lower GFR.

PMID- 15458464
TI  - Interdialytic weight gain in patients on hemodialysis is associated with dry
      mouth and thirst.
AB  - BACKGROUND: Patients receiving hemodialysis (HD) have to maintain a fluid
      restricted diet. Severe thirst can induce noncompliance to this diet, resulting
      in an increase of interdialytic weight gain (IWG = weight predialysis -
      postdialysis) associated with poor patient outcomes. Because oral dryness may
      contribute to experienced thirst, we investigated the possible relation between
      thirst, salivary flow rate, xerostomia, and IWG. METHODS: Unstimulated (UWS) and
      stimulated (CH-SWS) whole saliva were collected from 94 HD patients (64 men, 54.8
      +/- 15.5 years; 30 women, 59.5 +/- 18.7 years). Secretion rates of saliva were
      determined gravimetrically. Xerostomia was assessed with a validated Xerostomia
      Inventory (XI), and thirst with a newly developed Dialysis Thirst Inventory
      (DTI). RESULTS: Before dialysis, 36.2% of the patients had hyposalivation (UWS <
      or =0.15 mL/min). The XI scores had a positive relation with IWG (r=.250, P <
      0.001). Gender and age differences were observed for thirst, salivary flow rates,
      and xerostomia. The prevalence and severity of thirst and xerostomia were greater
      in younger subjects. Patients with urine output did not differ from those without
      urine output with respect to thirst, xerostomia, and IWG. Correlations were found
      between thirst (DTI) and both IWG and xerostomia (XI) (r=.329, P < 0.001,
      respectively; r=.740, P < 0.001). Other correlations were observed between
      xerostomia and both the salivary flow rate and total number of medications (r=
      .252, P < 0.05, respectively; r=.235, P <.05). CONCLUSION: In HD patients,
      xerostomia (XI) and thirst (DTI) are associated with a higher IWG. Our data
      provide evidence that, in HD patients, xerostomia is related to both salivary
      flow rate and thirst (DTI).

PMID- 15458465
TI  - Kinetics of urea and beta-microglobulin during and after short hemodialysis
      treatments.
AB  - BACKGROUND: Daily short hemodialysis (HD) is often prescribed by simply doubling
      treatment frequency and halving treatment time; however, the effect of this
      prescription approach on the equilibrated HD dose (urea eKt/V) and whole body
      clearance for beta(2)-microglobulin has not been established. METHODS: We
      compared urea and beta(2)-microglobulin kinetics during and 60 minutes after a
      short HD treatment and a conventional HD treatment in a crossover study on 22
      maintenance HD patients: 16 male and 6 female, 61 +/- 18 (mean +/- standard
      deviation) years of age. One patient in each treatment modality was excluded from
      certain analyses because of missing data. Short and conventional HD treatments
      were essentially identical, except for treatment times, which were 116 +/- 14 and
      241 +/- 27 minutes, respectively. Blood samples were collected at regular
      intervals during and after treatments, and additional blood and dialysate samples
      were collected at 60 minutes of treatment to evaluate dialyzer clearances.
      RESULTS: Plasma water urea clearances measured directly across the dialyzer
      during short and conventional HD treatments were not different (255 +/- 23 mL/min
      and 255 +/- 28 mL/min, respectively). The 60-minute postdialysis blood urea
      nitrogen concentration rebounded more (P < 0.01) after short HD than conventional
      HD (5.9 +/- 3.1 vs. 4.0 +/- 1.5 mg/dL, respectively). Calculated urea eKt/V
      values using the Daugirdas-Schneditz rate equation were not different from those
      measured during conventional HD using the 60-minute postdialysis concentration
      but significantly overestimated measured urea eKt/V values during short HD.
      Postdialysis rebound of beta(2)-microglobulin concentrations was variable but
      similar after short and conventional HD treatments (0.1 +/- 3.4 vs. 0.7 +/- 1.8
      mg/L, respectively). Whole body clearances of beta(2)-microglobulin calculated
      from predialysis and immediate (10-second) postdialysis serum concentrations
      during short and conventional HD treatments were not different from each other
      (42.9 +/- 24.1 vs. 41.9 +/- 22.4 mL/min, respectively). CONCLUSION: These
      observations show that the Daugirdas-Schneditz rate equation is accurate in
      predicting urea eKt/V during conventional, but not during short, HD. In contrast,
      whole body clearances of beta(2)-microglobulin during short and conventional HD
      treatments were similar. We conclude that calculation of accurate estimates of
      urea eKt/V, but not clearances of beta(2)-microglobulin, differ during short and
      conventional HD treatments.

PMID- 15458466
TI  - TNP-470, an angiogenesis inhibitor, suppresses the progression of peritoneal
      fibrosis in mouse experimental model.
AB  - BACKGROUND: In patients on long-term peritoneal dialysis (PD), angiogenesis and
      vasculopathy are observed in the peritoneum, and the degree of vascularization
      correlates with the area of fibrotic tissue, suggesting the involvement of
      angiogenesis in the progression of peritoneal fibrosis. The aim of the present
      study was to evaluate the effect of TNP-470, an anti-angiogenic compound, on the
      development of peritoneal fibrosis induced by chlorhexidine gluconate (CG).
      METHODS: Peritoneal fibrosis was induced by injection of CG into peritoneal
      cavity of Institute for Cancer Research (ICR) mice. TNP-470 was injected
      subcutaneously with CG. Mice were sacrificed, and peritoneal tissues were
      dissected out at days eight and 16 after CG and TNP-470 injection. The expression
      patterns of CD31 (as a marker of endothelial cells), vascular endothelial cell
      growth factor (VEGF), alpha-smooth muscle actin (as a marker of myofibroblasts),
      heat shock protein 47 (HSP47), type III collagen, F4/80 (as a marker of mice
      macrophages), proliferating cell nuclear antigen (PCNA), and cyclin-dependent
      kinase 2 (Cdk2) were examined by immunohistochemistry. RESULTS: CG-injected mice
      showed thickening of the submesothelial zone and increased number of vessels,
      myofibroblasts, and infiltrating macrophages. The expression levels of VEGF, type
      III collagen, and HSP47 were increased, and a large number of PCNA-positive cells
      and Cdk2-expressing cells were observed in the thickened submesothelial area.
      Treatment with TNP-470 suppressed the submesothelial zone thickening and reduced
      collagen III expression as well as angiogenesis. TNP-470 also decreased the
      number of VEGF-expressing cells, myofibroblasts, macrophages, PCNA-positive
      cells, and Cdk2-expressing cells. CONCLUSION: Our results indicate the
      involvement of angiogenesis in the progression of peritoneal fibrosis, and
      suggest that TNP-470 may be potentially useful for the prevention of peritoneal
      fibrosis through inhibition of angiogenesis and suppression of myofibroblast
      proliferation.

PMID- 15458467
TI  - Donor genomics influence graft events: the effect of donor polymorphisms on acute
      rejection and chronic allograft nephropathy.
AB  - BACKGROUND: Organs procured from deceased donors emanate from individuals with
      diverse genetic backgrounds. Donor organs, therefore, may vary in their response
      to injury and immune stimuli in a genetically determined manner. We assessed
      polymorphisms from 244 renal allograft donors to better understand the impact of
      donor polymorphisms on selected transplant outcomes. METHODS: Donor genomic DNA
      restriction fragment length polymorphisms were assayed for evidence of common
      cytokine [interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, TGF
      beta, interferon (IFN)-gamma] and chemokine (CCR2, CCR5) polymorphisms.
      Associations between donor polymorphisms and graft events were determined using
      chi-square, linear regression, and Kaplan-Meier analyses. RESULTS: Several
      genotypic polymorphisms demonstrated a modest association with acute rejection,
      including the transforming growth factor (TGF)-beta T/C codon 10 (P= 0.027) and
      the CCR5 G/A 59029 (P= 0.039) genes by chi-square analysis. Notably, the presence
      of the T allele in the IFN-gamma gene (+874) demonstrated a highly significant
      association with biopsy-proven chronic allograft nephropathy (P < 0.008). This
      association remained highly significant in a multiple linear regression model
      that incorporated biopsy-proven acute rejection as a covariate. CONCLUSION: These
      data suggest that many of the donor polymorphisms studied in this analysis may
      influence a recipient's immune response to a renal allograft. However, their
      greatest impact may be demonstrated in long-term outcomes.

PMID- 15458468
TI  - Analysis of the functional muscle-bone unit of the forearm in pediatric renal
      transplant recipients.
AB  - BACKGROUND: Renal transplantation in children and adolescents is associated with
      various skeletal complications. The incidence of spontaneous fractures appears to
      be increased, but the reasons for this are not entirely clear. Our objective was
      therefore to evaluate macroscopic bone architecture, mass, and strength by
      peripheral quantitative computed tomography (pQCT), a method that is not
      influenced by size-related artifacts. In addition, we investigated the muscle
      bone relationship in these patients because under physiologic conditions bone
      strength continually adapts to increasing mechanical loads, that is, muscle
      force. METHODS: In 55 patients (41 males) aged 15.8 +/- 4.1 years, we evaluated
      in a cross-sectional study 4.9 +/- 3.6 years after renal grafting bone mass,
      density, geometry, and strength of the radius, as well as forearm muscle size and
      strength, using pQCT at the proximal and distal radius, radiography of the second
      metacarpal shaft and hand dynamometry. Data were compared to a large cohort (N=
      350) of healthy children. RESULTS: Muscle mass and force were adequate for body
      size in pediatric renal transplant recipients. However, the radial bone was
      characterized by an inadequately thin cortex in relation to muscular force, as
      shown by a reduced height-adjusted cortical thickness both at the proximal (-0.83
      +/- 1.12 SDS) and distal radius (-0.52 +/- 1.69 SDS), the metacarpal shaft (-0.54
      +/- 1.35 SDS), and by a reduced relative cortical area (-0.90 +/- 1.13 SDS),
      while the mineralization of trabecular bone was unaltered. As a consequence of
      cortical thinning, the Strength-Strain Index that reflects the combined strength
      of trabecular and cortical bone was reduced in these patients. CONCLUSION: While
      bone mineral density of the forearm is not decreased in pediatric renal
      transplant recipients, bone strength in relation to muscular force is reduced.
      This alteration may contribute to the increased propensity for fractures in these
      patients.

PMID- 15458469
TI  - Renal transport proteins in excreted urine: gold mine or gold dust?

PMID- 15458470
TI  - Promise for gene therapy in obstructive nephropathy.

PMID- 15458471
TI  - Underuse of Hardy-Weinberg equilibrium.

PMID- 15458473
TI  - Regarding impact of epoetin alfa on clinical end points in patients with chronic
      renal failure: a meta-analysis.

PMID- 15458475
TI  - Mycophenolate mofetil in IgA nephropathy.

PMID- 15458477
TI  - The impact of serum uric acid on cardiovascular outcomes in the LIFE study.

PMID- 15458478
TI  - Hepatic iron in hemodialysis patients.

PMID- 15458479
TI  - Heterozygous NPHS1 or NPHS2 mutations in responsive nephrotic syndrome and the
      multifactorial origin of proteinuria.

PMID- 15458480
TI  - Different meanings of "glomerular tip lesion".

PMID- 15458482
TI  - How can we be sure that renal dysfunction after coronary angiography is just
      explained by contrast nephropathy?

PMID- 15458484
TI  - Atherosclerosis and uremic retention solutes.

PMID- 15458486
TI  - Human cryptosporidiosis: an update with special emphasis on the situation in
      Europe.
AB  - The genus Cryptosporidium consists of different species and genotypes which
      infect a wide range of hosts, including humans. The parasite is ubiquitous and
      lack of differentiation between the species and strains has made it difficult to
      track down sources of human and animal infections. Genetic analysis of strains
      and isolates has led to the redescription of Cryptosporidium with special
      consideration of the host specificity and possible ways of transmission to
      humans. Infection with the small oocysts usually occurs directly by faecal-oral
      transmission, water- or food-borne. In Europe water from different sources is
      frequently contaminated with oocysts. Generally, humans are most frequently
      infected with C. hominis in an anthroponotic cycle (especially in cases of
      infections imported from highly endemic (sub-) tropical regions) and the animal
      genotype (type II) of C. parvum in a zoonotic cycle which seems to play a major
      role in autochthonous infections in Switzerland, the UK and probably other
      European countries. Other species (such as C. felis or the avian species C.
      meleagridis and C. baileyi) and genotypes are rare in humans and mostly
      restricted to immunocompromised individuals who are highly susceptible to serious
      opportunistic cryptosporidial infections.

PMID- 15458487
TI  - Classical swine fever virus Strain 'C'. How long is it detectable after oral
      vaccination?
AB  - To determine the persistence period of C-strain vaccine virus in immunized
      animals, domestic pigs and wild boars were vaccinated orally and killed on
      different days post vaccinationem (dpv). Tissue samples were taken at necropsy
      from both species for detection of C-strain virus. From domestic pigs nasal swabs
      and faeces were also collected. During the investigation period (2-12 dpv)
      vaccine virus could never be detected in nasal secretions and in faeces of
      vaccinated domestic pigs. In contrast, C-strain virus was found in organs until
      day 8 pv in domestic pigs and until day 9 pv in wild boars. Whereas in domestic
      pigs virus was detected in tonsils, Ln. mandibularis or in spleen, in wild boar
      it only was found in tonsils. We conclude that C-strain vaccine virus is not
      detectable in wild boars longer than 10-12 days after intake of the vaccine
      baits.

PMID- 15458488
TI  - Early and cost-effective identification of high risk/priority control areas in
      foot-and-mouth disease epidemics.
AB  - Geo-referenced data from the 2001 Uruguayan foot-and-mouth disease (FMD) epidemic
      were explored to assess whether spatial analysis could lead to cost-benefit based
      policies. Four variables were analysed: (i) location and size of 4022 individual
      rural land parcels, of which 574 were infected over 60 days, (ii) animal density,
      (iii) percentage of dairy farms per county, and (iv) road density. Each variable
      was categorized into two to five classes (e.g. small/medium/large) and the
      proportion of cases per class reported at days 1-3 of the epidemic was compared
      with that reported at days 4-6. A higher proportion of cases was found at days 4
      6 than at days 1-3 in areas with: small and medium size land parcels, high animal
      density, > 20% farms specialized in dairy production, and high road density (P <
      0.03 for each). Each of these classes showed a greater proportion of cases at
      days 7-60 than the proportion of the total territory covered by each class's area
      (early case concentration ratios: 1.14-1.37). Land parcel clusters were indicated
      by Moran's I-test (P < 0.01). A new region was constructed by intersecting the
      four spatial classes associated with higher proportions of cases at days 4-6. At
      days 7-60, this region included 50.4% of all cases and represented 30.6% of the
      territory under study (final case concentration ratio: 1.65). The final area per
      case in this region was at least 33% lower and covered at least 45% less
      territory than any of the four single-variable approaches. Bio-statistical,
      multivariate spatial analysis of early cases may greatly increase the efficiency
      of epidemiologic policy.

PMID- 15458489
TI  - Immunogenicity of murein-associated proteins from temperature-stressed
      Streptococcus suis cultures.
AB  - We compared immunogenicity in pigs of whole cell lysate proteins (WCP) with
      murein-associated proteins (MAP) obtained from a virulent serotype 2 strain of
      Streptococcus (S.) suis grown at 32 or 42 degrees C. Protein fractions were
      tested for their ability to induce antibodies in 3-week-old piglets by enzyme
      linked immunosorbent assay and Western blot analysis. We found a significant
      increase in the antibody levels in all sera irrespective of the preparation used
      for immunization. However, alpha-WCP sera showed higher reactivities than alpha
      MAP sera, and piglets immunized with 32 degrees C preparations (alpha-32 sera)
      showed higher responses than those immunized with 42 degrees C preparations
      (alpha-42 sera). Western blot analysis revealed that alpha-WCP sera in part
      reacted with different proteins when compared with alpha-MAP sera. Furthermore,
      some proteins were only detected by alpha-32 but not by alpha-42 sera. In
      conclusion, the results demonstrate the immunogenicity of cell wall MAP of S.
      suis, and highlight the importance of considering growth conditions in the
      preparation of subunit vaccines.

PMID- 15458490
TI  - Lameness in piglets. Abrasions in nursing piglets and transfer of protection
      towards infections with Streptococci from sow to offspring.
AB  - A group of 175 newborn piglets were monitored with respect to development of
      abrasions and lameness. Lameness was diagnosed in 10.9% of the piglets. About
      every second litter was affected and around 75% of these diagnoses took place
      during the first 3 weeks of life. Skin lesions were present already on day 3.
      They increased in magnitude until day 10 and thereafter declined. They were
      generally bilateral and most commonly observed as abrasions over the carpal
      joints. Hocks, face and tails were affected in a similar way, but at lower
      magnitudes. Sole bruising was observed in 87% of the piglets on the third day of
      life, and moderate to severe lesions dominated until day 10. Thereafter the
      incidence decreased, indicating healing with time. Still 39% of the piglets were
      affected at day 17. There was a significant positive correlation between skin
      lesions of carpus and hock within all examination days in selected piglets with
      known identity (n = 48). Between day 10 and 17 significant positive correlations
      were found within all examination sites with exception of abdomen and teats. The
      offspring of sows treated against mastitis expressed more abrasions then piglets
      delivered by healthy sows and the mortality during the first 17 days postpartum
      was significantly higher among piglets delivered by sows treated for mastitis.
      The level of serum antibodies to Streptococcus equisimilis in eight dams
      decreased during the last month of gestation and a declining maternal immunity to
      S. equisimilis was demonstrated in all piglets (n = 47) during the first 5 weeks
      of life. During the first 2 weeks of life somewhat lower median levels of serum
      antibodies were recorded among the piglets that were treated against arthritis (n
      = 8).

PMID- 15458491
TI  - Virulence genes of Escherichia coli strains isolated from mastitic milk.
AB  - Escherichia coli, a Gram-negative environmental pathogen associated with bovine
      mastitis was isolated from the milk of 34 symptomatic cows that had been
      diagnosed with clinical mastitis. Eighty isolates were obtained over a 17-month
      period and these isolates were screened by DNA amplification for the following E.
      coli virulence genes: cnf1, cnf2, eaeA, eagg, einv, ltx1, stx1, stx2 and vt2e.
      Thirty of the bacterial isolates, obtained from 23 different cows, had toxin
      genes identified in their DNA. The most common virulence gene detected was stx1,
      with a prevalence of 31%, followed by cnf2 (7.5%), vt2e (6.25%) and eaeA (4%).
      The possession of different virulence genes by the bacterial isolates had no
      discernable impact on the health status of the cows as there was no correlation
      between the potential for toxin production by the E. coli isolates and the
      systemic clinical condition of the respective infected cows.

PMID- 15458492
TI  - Characterization of pathogenic Escherichia coli isolated from humans in Austria:
      phenotypes, toxin gene types and epidemiology.
AB  - One hundred and ten clinical Escherichia coli isolates of serovar O157 (n = 102)
      and O26 (n = 8) were characterized for the presence of putative virulence genes
      by PCR. All but one of these isolates contained the eae gene. The EHEC-hly gene
      could be detected in all E. coli O157 and in 50% of E. coli O26 isolates. Forty
      five (40.9%) of the 110 E. coli were positive for both stx(1) and stx(2) genes, 2
      (1.8%) isolates were positive for stx(1) and 57 isolates (51.8%) were positive
      for stx(2) only. Among the 102 stx(2) positive isolates, 14 (13.7%) E. coli O157
      contained also the stx(2c) variant gene. No other stx(2) variant was identified.
      Six clinical isolates (five E. coli O157:H7 and one E. coli O26) did not contain
      stx genes. Ten non-pathogenic E. coli isolates which were amplified as controls
      didn't contain any stx and eae gene but two of the ten strains contained the EHEC
      hly gene. By their growth on chromogenic media, all but two of 50 E. coli O157
      could be differentiated from eight E. coli O26 and 10 non-pathogenic E. coli.
      Sixty-one of the O157:H7 isolates were further subjected to pulsed-field gel
      electrophoresis (PFGE) which identified 49 distinguishable patterns. In five
      cases where contact infection among family members was suspected,
      indistinguishable PFGE patterns confirmed the epidemiological relatedness of the
      isolates. Moreover, two PFGE clusters were identified which comprised five and
      three strains, respectively. These findings indicate the occurrence of both
      family and diffuse outbreaks of E. coli O157 infections in Austria during recent
      years and demonstrate the need for molecular subtyping of these pathogens.

PMID- 15458493
TI  - Effects of subinhibitory concentrations of florfenicol on morphology, growth, and
      viability of Staphylococcus aureus.
AB  - Staphylococcus aureus strain Newman was investigated for changes in its growth
      pattern, its morphology and its viability when grown in the presence of 3
      microg/ml florfenicol (Ff). This concentration corresponds to the 0.75-fold
      strain-specific minimum inhibitory concentration (MIC). Under these conditions,
      S. aureus Newman showed a distinct retardation in its growth pattern and 20% dead
      cells were detected in a fluorescence microscopic viability assay. However,
      bactericidal activity - defined as a 3-log drop in the staphylococcal population 
      was not recorded at this Ff concentration. Further analysis of the cell wall
      revealed a significant increase in cell wall thickness of S. aureus Newman when
      grown in the presence of 3 microg/ml Ff. This might result in a compression of
      the protoplast with subsequent disruption of single staphylococcal cells.
      Accordingly, 20% of the staphylococcal cells analysed by electron microscopy
      proved to be disrupted. These observations suggest that Ff can cause a thickening
      of the cell wall accompanied by impaired viability of the staphylococcal cells.

PMID- 15458494
TI  - Influence of methods for Trichinella detection in pigs from endemic and non
      endemic European region.
AB  - A total of 1401 German and 226 Croatian pigs raised either indoors or outdoors
      were tested for Trichinella infection by direct and indirect detection methods. A
      10 g sample of diaphragm were examined for muscle larvae by the artificial
      digestion method; the species was determined by multiplex polymerase chain
      reaction (PCR). For detection of anti-Trichinella IgG, serum samples diluted
      1:100, and meat juice samples diluted 1:10, were tested by enzyme-linked
      immunosorbent assay. All German pigs and those Croatian pigs raised indoors
      proved to be Trichinella-negative by all methods. Muscle larvae were detected in
      a total of eleven of the Croatian pigs, which were raised on small outdoor farms.
      For eight isolates, PCR results demonstrated that recovered larvae were
      Trichinella spiralis. Anti-Trichinella-IgG was detected in serum and meat juice
      of digestion positive animals when the worm burdens exceeded 0.38 larvae per gram
      of muscle. Positive results in Croatian pigs indicate a higher risk of infection
      for outdoor farming in areas where Trichinella is endemic. Results of direct and
      indirect detection were compared and are discussed with special regard to
      specificity and sensitivity of methods.

PMID- 15458495
TI  - Clinical paratuberculosis as a cause for higher culling rate in cows with left
      displaced abomasum and diarrhoea in a holstein dairy herd.
AB  - The present report identifies a statistically significant (P < 0.001) higher
      postoperative culling rate in cows with left displaced abomasum (LDA) exhibiting
      diarrhoea, compared with cows with LDA and normal faeces from a large Holstein
      dairy herd (odds ratio = 34). Paratuberculosis was histopathologically confirmed
      in 77.0% of cows with LDA exhibiting diarrhoea.

PMID- 15458496
TI  - Collinearity in linear regression is a serious problem in oral health research.
AB  - The aim of this article is to encourage good practice in the statistical analysis
      of dental research data. Our objective is to highlight the statistical problems
      of collinearity and multicollinearity. These are among the most common
      statistical pitfalls in oral health research when exploring the relationship
      between clinical variables using multiple regression analysis. We hope that this
      article will show why these problems arise and how they can be avoided and
      overcome. Examples from the periodontal literature will be used to illustrate how
      collinearity and multicollinearity can seriously distort the model development
      process as a result of the phenomenon of mathematical coupling. Knowledge of
      these problems can help to eliminate misleading results and improve any
      subsequent interpretations. Regression analyses are useful tools in oral health
      research when their limitations are recognized. However, care is required in
      planning and it is worthwhile seeking statistical advice when formulating the
      study's research questions.

PMID- 15458497
TI  - Human jaw muscle strength and size in relation to limb muscle strength and size.
AB  - The aim of the present study was to investigate to what extent general factors
      (e.g. genotype, hormones) and factors at the craniofacial level (e.g.
      craniofacial size, jaw muscle architecture) contribute to the size and strength
      of the jaw muscles. A strong relationship of jaw muscle size and strength with
      that of other muscles would argue for general influences, whereas a weak
      relationship would argue for craniofacial influences. In 121 adult individuals,
      moments of maximal bite force, arm flexion force and leg extension force were
      measured. In addition, thicknesses of jaw muscles, arm flexor muscles and leg
      extensor muscles were measured using ultrasound. Relationships were assessed by
      using a principal component analysis. In females, one component was found in
      which all force moments were represented. Bite force moment, however, loaded very
      low. In males, two components were found. One component loaded for arm flexion
      and leg extension moments, the other loaded for bite force moments. In both
      females and males, only one component was found for the muscle thicknesses in
      which all muscle groups loaded similarly. It was concluded that the size of the
      jaw muscles was significantly related to the size of the limb muscles, suggesting
      that they were both subject to the same general influences. Maximal voluntary
      bite force moments were not significantly related to the moments of the arm
      flexion and leg extension forces, suggesting that besides the general influence
      on the muscle size, variation in bite force moment was also influenced by local
      variables, such as craniofacial morphology.

PMID- 15458498
TI  - A retrospective study of dental behavior management problems in children with
      attention and learning problems.
AB  - Attention and learning problems in children are common. The aim of this study was
      to investigate whether children with attention and learning problems had more
      dental behavior management problems (BMP), more cancelled and missed
      appointments, and more traumatic dental injuries compared with a control group.
      All children born in 1991 attending mainstream schools (n = 555) in one Swedish
      municipality were screened for behavioral and learning problems. Conners' 10-item
      questionnaire and a questionnaire focused on executive and learning problems were
      used. A total of 128 screen-positive patients were index cases and 131 screen
      negative patients control cases. The dental records of these children were
      studied from 1 yr of age until the child reached 10 yr. Behavior management
      problems on at least one occasion were more common in the index group (54% vs.
      37%). The percentage of appointments at which the children exhibited BMP was
      higher in the index group (13% vs. 7%). No differences were found for cancelled
      or missed appointments or dental traumatic injuries between the two groups. In
      conclusion, the results of this study show that children with attention and
      learning problems had significantly more dental behavior management problems
      compared with a control group.

PMID- 15458499
TI  - Microbiological evaluation of dental unit water systems in general dental
      practice in Europe.
AB  - A range of opportunistic pathogens have been associated with dental unit water
      systems (DUWS), particularly in the biofilms that can line the tubing. This study
      therefore aimed to assess the microbiology of DUWS and biofilms in general dental
      practices across seven European countries, including the United Kingdom (UK),
      Ireland (IRL), Greece (GR), Spain (ES), Germany (D), Denmark (DK) and the
      Netherlands (NL). Water supplied by 51% of 237 dental unit water lines exceeded
      current American Dental Association recommendations of < or = 200 colony-forming
      units (CFU) ml(-1). Microbiological loading of the source waters was between 0
      (Denmark, the Netherlands and Spain) and 4.67 (IRL) log CFU ml(-1); water line
      samples from the DUWS ranged from 1.52 (ES) to 2.79 (GR) log CFU ml(-1); and
      biofilm counts ranged from 1.49 (GR) to 3.22 (DK) log CFU.cm(-2). Opportunistic
      pathogens such as legionellae (DK and ES), including Legionella pneumophila SG1
      (DK and GR), and Mycobacterium spp. (DK, NL, GR, D and ES) were recovered
      occasionally. Presumptive oral streptococci (ES and NL), oral anaerobes (GR),
      Candida spp. (UK, NL and ES) and blood (GR and IRL) were detected at relatively
      low frequencies, but their presence indicated a failure of the 3-in-1
      antiretraction valve, leading to back siphonage of oral fluids into the water and
      biofilm phase. These findings confirm that a substantial proportion of DUWS have
      high levels of microbial contamination, irrespective of country, type of
      equipment and source water. The study emphasizes the need for effective
      mechanisms to reduce the microbial burden within DUWS, and highlights the risk of
      occupational exposure and cross-infection in general dental practice.

PMID- 15458500
TI  - Relationship between bacterial infection and evaluation using a laser
      fluorescence device, DIAGNOdent.
AB  - The aim of this in vitro study was to investigate the relationship between
      bacterial infections in carious dentin when detected by two different methods --
      polymerase chain reaction (PCR), and a laser fluorescence device, DIAGNOdent.
      Dentin was removed every 300 micro m in the direction of the pulp chamber in 10
      extracted molars with occlusal dentin caries and 3 extracted sound molars. Dentin
      surfaces were evaluated using DIAGNOdent, and dentinal tissue samples were
      removed by using a round bur before and after each removal. Bacterial DNA in the
      dentinal tissues was detected by PCR, using primers based on the nucleotide
      sequence of a conserved region of the 16S rDNA, and yielded a PCR product of 466
      bp. The rates of bacterial detection increased as the DIAGNOdent values
      increased. In the 10 specimens, the lowest DIAGNOdent value at which bacteria
      were detected was 15.6; at DIAGNOdent values below 15.6, no bacteria were
      detected. The results of a receiver operating characteristic (ROC) curve for the
      DIAGNOdent values showed that the area under the ROC curve was 0.91. This study
      clarified the relationship between the DIAGNOdent values of dentin caries and the
      rates of bacterial detection.

PMID- 15458501
TI  - Protective effect of salivary nitrate and microbial nitrate reductase activity
      against caries.
AB  - To test the hypothesis that a combination of high salivary nitrate and high
      nitrate-reducing capacity are protective against dental caries, 209 children
      attending the Dental Institute, Barts and The London NHS Trust were examined.
      Salivary nitrate and nitrite levels, counts of Streptococcus mutans and
      Lactobacillus spp., and caries experience were recorded. Compared with control
      subjects, a significant reduction in caries experience was found in patients with
      high salivary nitrate and high nitrate-reducing ability. Production of nitrite
      from salivary nitrate by commensal nitrate-reducing bacteria may limit the growth
      of cariogenic bacteria as a result of the production of antimicrobial oxides of
      nitrogen, including nitric oxide.

PMID- 15458502
TI  - Insoluble zinc, cupric and tin pyrophosphates inhibit the formation of volatile
      sulphur compounds.
AB  - Oral malodour is mainly a result of the production of volatile sulphur compounds
      (VSC). The present study was concerned with investigating the anti-VSC effect of
      insoluble pyrophosphates (PP) of zinc, copper(II) and tin(II). The hypothesis to
      be tested was that the sulphide anions produced when VSC are solubilized in water
      have a higher affinity for the respective metal ions than the PP anion. The anti
      VSC effects of insoluble PP were compared with the corresponding soluble metal
      salts using three in vitro methods: saliva putrefaction; dialysis of a suspension
      of PP and saliva against water; and analysis of water containing hydrogen
      sulphide and methyl mercaptan gases, and gases in the headspace. The levels of
      VSC were analysed by gas chromatography in the first and third methods, and
      released metal ions were analysed by atomic absorption spectroscopy in the
      second. The results showed that: the insoluble metal PP inhibited VSC formation
      in saliva by 99-100%; under dialysis, only minute amounts of metal ions are
      released from the combination of PP and saliva; and the PP lost their metal
      cations in water containing dissolved gases and inhibited VSC formation. Hence,
      the results support the experimental hypothesis. Sulphide ions are obviously very
      strong ligands for these metal ions.

PMID- 15458503
TI  - Deletion of gtfC of Streptococcus mutans has no influence on the composition of a
      mixed-species in vitro biofilm model of supragingival plaque.
AB  - Glucosyltransferases from Streptococcus mutans are thought to play an important
      role in bacterial adherence to the tooth surface. The goal of the present study
      was to determine the effect of the deletion of the gtfC gene, which encodes a
      glucosyltransferase that catalyses primarily the formation of insoluble glucan
      (mutan), on colonization of S. mutans in a mixed-species biofilm model of
      supragingival plaque. A gtfC deletion mutant of S. mutans UA159 grew poorly in
      biofilms on a polystyrene surface in Todd-Hewitt medium containing sucrose, but
      biofilm formation in the semi-defined fluid universal medium (FUM) was not
      affected. The S. mutans gtfC mutant colonized with the same efficiency as the
      wild-type strain when grown together with five other species in a mixed-species
      biofilm on hydroxyapatite in a mixture of FUM and saliva with pulses of sucrose
      and showed the same ability to demineralize enamel in vitro. Colonization of
      mutant and wild-type strains was also equal in an association experiment in
      specific-pathogen-free rats. However, the gtfC mutant gave rise to more dentinal
      fissure lesions and smooth surface caries than the wild-type strain; this could
      be caused by a change in diffusion properties as a result of to the lack of
      mutan.

PMID- 15458504
TI  - Regulation of secretion of osteoprotegerin in rat dental follicle cells.
AB  - Tooth eruption requires alveolar bone resorption and formation, both of which
      appear to be regulated by the dental follicle. Osteoclastogenesis needed for this
      bone resorption appears to occur as a result of a reduction in the expression of
      the osteoprotegerin (OPG) gene in the dental follicle at a specific time. This
      reduction in expression is mediated in vitro in the follicle cells by colony
      stimulating factor-1 (CSF-1) and parathyroid hormone-related protein (PTHrP).
      Using enzyme-linked immunosorbent assays and immunoblotting, this study shows
      that the reduction in expression of OPG after incubation of the dental follicle
      cells in either CSF-1 or PTHrP also results in a reduction in its secretion. We
      also show, by laser capture microdissection, that PTHrP is expressed in vivo in
      the stellate reticulum such that it could inhibit OPG expression via a paracrine
      effect on the follicle. Bone formation is enhanced by OPG secretion, and
      incubation of the follicle cells with bone morphogenetic protein-2 (BMP-2)
      enhances OPG secretion. Thus, a reduction in secretion of the OPG protein at
      defined times may promote the osteoclastogenesis and alveolar bone resorption
      needed for eruption, and enhancement of OPG secretion at other times may promote
      alveolar bone formation.

PMID- 15458505
TI  - Delivery of cytolethal distending toxin B induces cell cycle arrest and apoptosis
      in gingival squamous cell carcinoma in vitro.
AB  - The cytolethal distending toxin (Cdt) from Actinobacillus actinomycetemcomitans
      consists of three proteins, CdtA, CdtB, and CdtC, which are responsible for cell
      cycle arrest and apoptosis. In the present study, local delivery systems of
      recombinant CdtB and CdtB-expressing plasmid were established using Ca9-22, human
      gingival squamous cell carcinoma cell line. When CdtB was delivered to Ca9-22
      cells using a BioPORTER, a 32-kDa protein was detected by Western blotting, and
      G2 cell cycle arrest and apoptosis occurred. In addition, the CdtB delivered
      upregulated the expression of phosphorylated p53 and the cyclin-dependent kinase
      inhibitor p21(CIP1/WAF1) in Ca9-22 cells, suggesting that these intracellular
      molecules might contribute to the induction of G2 cell cycle arrest and
      apoptosis. When the CdtB-expressing plasmid was transfected into Ca9-22 cells by
      lipofection or electroporation, CdtB (32 kDa) was clearly detected. Further, TdT
      mediated dUTP nick end labeling positive cells were observed after transfection
      of the CdtB-expressing plasmid. These findings indicated that delivery of the
      CdtB protein and transfection of the cdtB gene induced cell cycle arrest and
      apoptosis in Ca9-22 cells in vitro, and we conclude that it may be possible to
      induce apoptosis in human gingival squamous cell carcinoma by electroporation of
      the cdtB gene.

PMID- 15458506
TI  - Dentin adhesion and microleakage of a resin-based calcium phosphate pulp capping
      and basing cement.
AB  - An experimental resin-based bioactive calcium phosphate cement, intended as a
      pulp capping and basing material, was evaluated for dentin shear bond strength
      and microleakage. The interfacial morphology was examined by scanning electron
      microscopy (SEM). For microleakage, dentin cavities without (Group A) or after
      (Group B) acid etching were restored with the calcium phosphate cement. A resin
      based calcium hydroxide (VLC Dycal; Group C) was used as control material
      according to the manufacturer's instructions. After water storage and
      thermocycling, the microleakage was scored using a AgNO(3) staining procedure.
      For the shear bond strength, flat exposed dentin surfaces were treated as for the
      microleakage test. Metal irises pressed against the dentin surface were filled
      with the cements, which were photocured. Both tests were carried out after 1 wk.
      While acid etching did not result in significantly greater microleakage, it led
      to higher shear bond strength, and allowed, as shown by SEM, the formation of a
      hybrid layer and resin tags. Both groups treated with the calcium phosphate
      cement had significantly lower microleakage scores and higher mean shear bond
      strength values than the groups treated with the control material.

PMID- 15458507
TI  - Effects of additional and extended acid etching on bonding to caries-affected
      dentine.
AB  - This study evaluated the effects of additional and extended acid etching on
      microtensile bond strength ( micro TBS) of two adhesive systems to sound (SD) and
      caries-affected dentine (CAD). Flat surfaces of CAD surrounded by SD of 36
      extracted carious third molars were assigned to four treatments (i): self-etching
      adhesive system (Clearfil SE Bond) applied to dentine surfaces following
      manufacturer's instructions (MI); (ii) after additional etching for 15 s (35%
      phosphoric acid, PA); (iii) total-etch one-bottle adhesive (Single Bond) applied
      to dentine surfaces following MI; or (iv), after etching for 45 s with PA.
      Composite 'blocks' were built on bonded surfaces and restored teeth were
      vertically sectioned to obtain bonded slices of 0.7 mm thick. Slices were trimmed
      to create hourglass-shaped specimens (cross-sectional area of 1 mm(2)), which
      were tested under tension in a universal testing machine. Additional CAD and SD
      samples were prepared for scanning electron microscopy observations. Additional
      and extended etching significantly increased micro TBS to CAD; however, micro TBS
      of both adhesives to CAD were significantly lower than to SD. Additional and
      extended etching can improve bonding to CAD; however, adhesives applied on SD
      showed the best results for bonding.

PMID- 15458508
TI  - Crack closure on rehydration of glass-ionomer materials.
AB  - Moisture-sensitivity of immature glass-ionomer cements suggests that hydration
      induced volumetric expansion might close and potentially heal established cracks.
      Crack closure in glass-ionomer cements (GICs) was observed following rehydration.
      Circular cavities were prepared in 15 teeth: 10 were restored with resin-modified
      GICs (5 with Fuji II LC and 5 with Photac-Fil) and 5 were restored with a
      conventional GIC (Fuji IX); all were dehydrated for 1 min with air and imaged
      immediately by confocal microscopy. Crack formation in each was located, after
      which water was placed on the surface and observed for 15 min via a CCD camera.
      Dehydration caused cracks with measurable gaps, while rehydration resulted in
      varying degrees of closure: closure was limited in the conventional GIC, and
      complete or near complete along part/s of the crack in the resin-modified GICs.
      In all, closure movement became imperceptible after the first 10 min. Statistical
      analysis indicated no significant difference between the closure behavior of all
      materials. However, the resin-modified GICs appeared to show a greater potential
      for closure of established cracks than the conventional GIC upon rehydration.

PMID- 15458509
TI  - Prognostic significance of vascular endothelial growth factor immunoexpression in
      the context of adverse standard prognostic factors in multiple myeloma.
AB  - OBJECTIVES: Vascular endothelial growth factor (VEGF) acts in several steps of
      multiple myeloma (MM) pathogenesis and it is an important mediator of tumor
      angiogenesis. The aim of this study was to examine the prognostic significance of
      VEGF immunoexpression in the context of standard prognostic factors present in a
      cohort of advanced MM patients. METHODS: Fifty untreated MM patients were
      enrolled from May 2000 to December 2002. Bone marrow sections were subjected to
      morphologic assessment and immunohistochemical studies with antibodies against
      CD34 and VEGF. Angiogenesis was measured by microvessel density (MVD) and
      stratified into high (MVD > or = 20) and low angiogenesis status (MVD < 20). VEGF
      immunoreactivity was examined on the basis of intensity and percentage of
      positive plasma cells (PC). RESULTS: Ninety-four percent of patients presented
      advanced disease at diagnosis. Median PC marrow infiltration was 80%. Twelve
      percent of patients presented plasmablastic morphology. Low angiogenesis was
      present in 27% of patients, while high angiogenesis was present in 73%. Twenty
      nine percent of patients had VEGF < 10% and 71% had VEGF > or = 10%. Weak
      intensity VEGF was observed in 34% of cases, while 37% had moderate/strong VEGF
      intensity. Although VEGF had prognostic impact on overall survival (OS) and event
      free survival (EFS) in univariate analysis, multivariate analysis identified only
      plasmablastic morphology and elevated serum lactate dehydrogenase (LDH) level as
      independent prognostic factors to predict OS (P = 0.04 and P = 0.02,
      respectively). With regard to EFS, although VEGF showed statistical trend to
      influence survival (P = 0.08), the parameters of independent prognostic value
      were also plasmablastic morphology (P = 0.01) and elevated LDH level (P = 0.01).
      CONCLUSION: Our findings underline the frequent expression of VEGF in advanced
      stage MM and the greater prognostic information of simple and readily available
      factors, namely plasmablastic morphology and elevated LDH. Moreover, despite the
      absence of prognostic importance in multivariate analysis, VEGF and its receptors
      remain promising therapeutic targets in MM.

PMID- 15458510
TI  - Is higher income and educational status associated with poorer outcome in
      patients with Hodgkin's disease?
AB  - OBJECTIVES: The aim of the study was to determine the impact of socioeconomic
      status on relapse-free survival (RFS) in patients with Hodgkin's disease.
      METHODS: A number of factors were analyzed for their impact on relapse-free and
      overall survival in Hodgkin's disease using Cox regression. These factors
      included socioeconomic status (as defined by education and income), different
      treatment modalities and established clinical risk factors [e.g. age at
      diagnosis, stage of disease, involvement of three or more lymph nodes, presence
      or absence of a large mediastinal mass, E stages or elevation of erythrocyte
      sedimentation rate (ESR)]. The study used an initial sample of 126 patients
      recruited between 1969 and 1995 and a larger sample of 218 patients (recruited
      until 2002). Clinical data on disease and treatment characteristics were
      collected from medical records. RESULTS: In a univariate analysis, the following
      parameters had impact on RFS: treatment modality (combined treatment resulted in
      an improved RFS compared with patients treated with chemo- or radiotherapy
      alone), educational status and income. The 5- and 10-yr relapse-free survival
      rates were found to increase with decreasing educational level and decreasing
      average income per month. These results were significant in the initial and total
      samples and were also significant using multivariate analysis (hazard ratio for
      highest vs. lowest education group: 5.88; 95% confidence interval 1.87-18.52; for
      highest vs. lowest income group: 4.36; 95% confidence interval 1.35-14.05).
      CONCLUSION: Hodgkin's disease appears to be a striking exception from the usual
      positive correlation between high socioeconomic status and favorable treatment
      outcome in patients suffering from tumor. It is suggested that future studies on
      tumor genetics and biology and more detailed analysis of further socioeconomic
      parameters may be useful in clarifying this observation.

PMID- 15458511
TI  - Tracking the follicular lymphoma cells in flow cytometry: characterisation of a
      new useful antibody combination.
AB  - OBJECTIVES: Follicular lymphoma (FL) is the most common adult non-Hodgkin's
      lymphoma. Diagnosis is based on morphology and can be confirmed by cytogenetic,
      flow cytometry (FCM) or molecular studies. Despite all these complementary
      approaches, diagnosis sometimes remains difficult. The purpose of the present
      work was to characterise the expression of new specific follicular cells markers
      which allows us to target specifically the abnormal FL cell population in FCM.
      METHODS: A total of 153 samples from healthy subjects and from patients with
      chronic B-cell lymphoproliferative disorders were analysed by FCM in the same
      conditions for purpose of comparison. RESULTS: We showed that CD44 is weakly
      expressed in FL cells compared with peripheral blood mononuclear cell from normal
      blood donors and others cells from B lymphoproliferative diseases. We
      nevertheless observed bone marrow samples where some immature B-cell population
      express CD44 with lower fluorescence intensity. Therefore, we developed a double
      antibody combination, using CD44 and CD38, which allowed us to separate the
      normal immature cells from the pathological population using FCM. CONCLUSION:
      This new phenotypic approach offers an accurate (sensitivity and specificity of
      93% and 96%, respectively), fast and low sample consuming method for the
      diagnosis of FL.

PMID- 15458512
TI  - Adult T-cell leukemia predominantly involving exocrine glands.
AB  - OBJECTIVES: We describe a rare case of adult T-cell leukemia (ATL) presenting
      with dry mouth and swelling of bilateral parotid and submandibular glands. The
      unusual involvement of these exocrine glands by malignant cells prompted us to
      conduct a detail characterization of these infiltrating and circulating leukemic
      T cells, which may provide insight to the pathogenesis of exocrine involvement in
      ATL. METHODS: Immunophenotyping of peripheral ATL cells and microscopic
      examinations of various organs prepared by autopsy were performed. Analysis of
      the repertoire of T-cell receptor (TCR) of parotid gland-infiltrating ATL cells
      using molecular and immunohistochemical examinations were also performed.
      RESULTS: Microscopic examinations of various organs prepared by autopsy revealed
      the predominant and specific exocrine gland infiltration of ATL cells. Reverse
      transcription-polymerase chain reaction (RT-PCR) followed by both TCR
      spectratyping and complementary determining region (CDR)-3 sequencing analysis of
      TCR Vbeta of parotid gland-infiltrating T cells revealed a relatively restricted
      but not single usage of TCR Vbeta. Immunohistochemical analyses of parotid gland
      specimens detected only a small number of TCR Valphabeta-positive cells in
      parotid gland-infiltrating ATL cells. CONCLUSIONS: The predominant infiltration
      of ATL cells in exocrine glands implied that these T cells recognized exocrine
      gland-specific antigen. However, the absence of both TCR Vbeta mRNA transcripts
      and TCR Valphabeta protein expression in most ATL cells suggested that antigen
      recognition via TCR may not have played a major role in adhesion and subsequent
      infiltration into the exocrine glands in this patient. These results provide
      important background information to further elucidate the pathogenesis of
      exocrine gland-specific inflammation.

PMID- 15458513
TI  - Lipoteichoic acid derived from Enterococcus faecalis modulates the functional
      characteristics of both normal peripheral blood leukocytes and native human acute
      myelogenous leukemia blasts.
AB  - OBJECTIVES: Several case reports have described complete hematological remissions
      for patients with otherwise untreated acute myelogenous leukemia (AML) who
      receive hematopoietic growth factor therapy during complicating bacterial
      infections. This may be caused by indirect cytokine effects, but direct effects
      of infecting agents on the malignant cells are also possible because bacterial
      molecules can bind to specific receptors expressed by normal and malignant
      leukocytes. Lipoteichoic acid (LTA) is a cell wall component of gram-positive
      bacteria, and it can activate normal immunocompetent cells through binding to
      specific cell membrane receptors. METHODS: We investigated effects of LTA derived
      from Enterococcus faecalis on in vitro cultured (i) normal peripheral blood
      mononuclear cells (PBMC); (ii) remaining T cells derived from patients with
      hematologic malignancies and chemotherapy-induced leukopenia; and (iii) native
      human AML cells. RESULTS: Increased interleukin 1beta (IL1beta) and IL8 release
      by in vitro cultured normal PBMC was observed after stimulation with LTA at
      concentrations > or =5 microg/mL; these levels were lower than for
      lipopolysaccharide (LPS)-stimulated cells and LTA antagonized LPS-induced
      cytokine release by normal PBMC. In most cases LTA did not alter T-cell
      proliferation for patients with chemotherapy-induced leukopenia. The LTA effects
      on AML blasts were investigated for 62 consecutive patients. LTA altered either
      cytokine (granulocyte-macrophage colony-stimulating factor + stem cell factor +
      IL3)-dependent proliferation or the release of IL1beta/IL8 for 23 patients; the
      effects were divergent but increased proliferation/cytokine levels were most
      commonly observed. CONCLUSION: The LTA derived from E. faecalis can modulate the
      functional characteristics of normal leukocytes and native human AML blasts.

PMID- 15458514
TI  - Flow cytometric detection of accelerated telomere shortening in myelodysplastic
      syndromes: correlations with aetiological and clinical-biological findings.
AB  - Using quantitative fluorescence in situ hybridisation and flow cytometry (flow
      FISH), we investigated the biological and clinical relevance of telomere length
      in 55 patients affected by myelodysplastic syndromes (MDS) compared with 55 sex-
      and age-matched controls. We found that telomere fluorescence in MDS
      granulocytes, and CD34+ cells did not decline with age as in normal controls and
      that MDS granulocytes and CD34+ cells had significantly shorter telomeres than
      healthy controls. A significant higher incidence of cases with intermediate
      unfavourable cytogenetics and International Prognostic Scoring System (IPSS) int
      2/high-risk group was observed among patients with lower telomere fluorescence.
      We also found that apoptosis in CD34+ cells was significantly higher in IPSS int
      1 low-risk patients when compared with IPSS int-2 high-risk cases and healthy
      controls and that CD34+ cell telomere fluorescence directly correlated with CD34+
      cell apoptosis. Reduced telomere fluorescence was associated with a history of
      occupational exposure to toxic agents and with worse survival in univariate and
      multivariate analyses. Our results suggest that flow-cytometry assessment of
      telomere dynamics may represent a valuable tool in the biological and clinical
      prognostic characterisation of MDS disorders.

PMID- 15458515
TI  - Cardiac status in well-treated patients with thalassemia major.
AB  - OBJECTIVE: To assess cardiac status in a large group of patients with thalassemia
      major who had been treated in a standard way since their early infancy with
      intensive transfusions and deferoxamine chelation therapy and who had good
      compliance with this regimen. METHODS AND RESULTS: We assessed clinically and
      echocardiographically 202 thalassemia major patients aged 27.3 +/- 6.3 yr and 75
      age and sex-matched healthy controls. Overt cardiac disease was encountered in 14
      patients (6.9%), including 5 (2.5%) with congestive heart failure, aged 26-37 yr,
      and 9 with systolic left ventricular (LV) dysfunction, aged 23-37 yr. Ten
      patients (5.0%) had a history of pericarditis. Left atrial and LV diameters, LV
      mass and cardiac output were significantly higher in patients than in controls,
      while peripheral resistance and LV afterload were significantly lower. Relative
      LV wall thickness did not differ between patients and controls, but it was
      significantly lower in patients with overt cardiac disease compared to those
      without (P < 0.05). Restrictive LV filling was observed in 37.6% of patients and
      was significantly more frequent in cases with overt cardiac disease (P < 0.01).
      Pulmonary hypertension was practically absent. Hematological parameters and
      pulmonary artery pressure levels were not independently associated with the
      presence of overt cardiac disease. CONCLUSION: Strict lifelong adherence to the
      standard transfusion and deferoxamine therapy reduces considerably the occurrence
      of heart failure, LV dysfunction and pericarditis, prevents early heart failure
      and pulmonary hypertension, but does not eliminate completely cardiac disease in
      patients with thalassemia major.

PMID- 15458516
TI  - Development of hepatosplenic gammadelta T-cell lymphoma with pancytopenia during
      early pregnancy: a case report and review of the literature.
AB  - Lymphomas rarely develop during pregnancy, but hepatosplenic gammadelta T-cell
      lymphoma (HSgammadeltaTCL) is extremely rare. We encountered a case of T-cell
      intracellular antigen-1 (TIA-1) positive and granzyme B-positive HSgammadeltaTCL
      that developed early during the course of pregnancy. The patient was a 31-yr-old
      female who was referred to our hospital because of pancytopenia and splenomegaly
      at the time of the14th week of her gestation. Her pancytopenia and
      hepatosplenomegaly worsened and she became fibril at the 27th week of gestation
      and Cesarean section was performed at the 29th week. Histopathological
      examination of the spleen, which was resected 28 d after delivery for a
      diagnostic purpose, revealed medium to large-sized nodules composed of dense
      proliferation of lymphoid cells having round to oval-shaped nuclei and abundant
      weakly eosinophilic cytoplasm. They were CD3epsilon+, mCD3+, CD4-, CD8-, CD56+,
      CD79a-, T-cell receptor (TCR)-gammadelta protein+, TIA-1+, and granzyme B+ by
      either immunohistochemistry or flow cytometry. Clonal rearrangement of TCR-gamma
      genes without such rearrangement of TCR-delta and TCR-beta genes was confirmed by
      Southern blot hybridization. Thus, the patient was diagnosed as having
      HSgammadeltaTCL, and combination chemotherapy was initiated. She is currently in
      partial remission. To our knowledge, this is the first case report of
      HSgammadeltaTCL that developed during pregnancy. Pathogenesis of pregnancy
      associated lymphoma is not known, but it is possible that maternal immunity
      during pregnancy or a hormonal imbalance, such as a change in the progesterone
      level, induces the development of lymphoma. Pregnancy-associated lymphoma is
      resistant to standard chemotherapy and is associated with poor prognosis.
      Therefore, it is important to accumulate clinicopathologic data of such cases for
      the development of a treatment modality.

PMID- 15458517
TI  - Acquired amegakaryocytic thrombocytopenia associated with proliferation of
      gamma/delta TCR T-lymphocytes and a BCR-ABL (p210) fusion transcript.
AB  - Acquired amegakaryocytic thrombocytopenia (AATP) in adults is a rare disorder
      characterized by severe thrombocytopenia and decreased or absent megakaryocytes
      in an otherwise normal bone marrow. We present a 44-yr-old man in whom the
      diagnosis of AATP was established in January 2001. Immunophenotyping of the
      peripheral blood lymphocytes showed a relative increase in the subpopulation of
      gamma/delta T-cell receptor (TCR) positive (gamma/delta TCR(+)) and (CD4, CD8)
      negative T lymphocytes, and PCR suggested a monoclonal pattern of TCR gamma chain
      gene rearrangement. Cytogenetic examination of his bone marrow cells showed a
      normal male karyotype but RT-PCR analysis revealed a BCR-ABL (p210) fusion
      transcript. The inhibition of CFU-Mk growth mediated by the patient's T
      lymphocytes indicated that the pathogenic mechanism for AATP could be an
      immunological attack on megakaryocyte progenitors where the gamma/delta TCR
      positive T lymphocytes are directly involved. The case emphasizes the complex
      association of T-lymphocyte monoclonal proliferation and AATP.

PMID- 15458518
TI  - Prolonged course of pure red cell aplasia after erythropoietin therapy.
AB  - Pure red cell aplasia (PRCA) caused by neutralising anti-erythropoietin
      antibodies is a very rare disease. Since 1998, an increased incidence of PRCA in
      patients with kidney failure following treatment with recombinant human
      erythropoietin (rhEpo) has been reported, mostly in Europe. In most cases, PRCA
      was cured by immunosuppressive therapy, immunoglobulins, plasmapheresis or renal
      transplantation. We report an exceptionally prolonged course of PRCA over 68
      months despite renal transplantation and different immunosuppressive regimens.

PMID- 15458519
TI  - Long-term alpha interferon treatment is effective on anaemia and significantly
      reduces iron overload in congenital dyserythropoiesis type I.
AB  - Interferon has been shown to be an effective treatment of congenital
      dyserythropoiesis type I (CDA-I), but the optimal dose and the feasibility of
      this treatment remains to be determined. Here, in a 9-yr follow-up of a single
      patient, we show that interferon remains active during such a long period. The
      optimal dose of conventional alpha interferon could be evaluated at 2 million
      units twice a week. Pegylated interferon could be used as well at a dose of 30
      microg/wk. During interferon treatment, serum and erythrocyte ferritin levels
      decreased progressively, and remained inversely correlated with haemoglobin
      levels. On repeated liver biopsies, iron overload could be normalized. Low dose
      interferon is a long-term treatment of CDA-I, and allows a significant decrease
      in iron overload, that could be interesting even in patients who are only
      moderately anaemic.

PMID- 15458520
TI  - Evan's syndrome complicating multicentric Castleman's disease -- dramatic
      response to rituximab.

PMID- 15458521
TI  - t(8;14) Mature B-cell (Burkitt's) lymphoma/leukaemia with atypical morphology in
      a paediatric patient.

PMID- 15458523
TI  - Highly purified 1000-cSt silicone oil for treatment of human immunodeficiency
      virus-associated facial lipoatrophy: an open pilot trial.
AB  - BACKGROUND: Among human immunodeficiency virus-infected individuals, facial
      lipoatrophy has become epidemic. Those affected are stigmatized, leading to
      psychological distress, social and career impediments, and impaired compliance to
      human immunodeficiency virus medications. Temporary treatment options are limited
      by excessive cost, necessity of frequent treatments, and lack of a natural look
      or feel beneath the skin. Affected patients require more persistent, affordable,
      safe, and effective treatment options. OBJECTIVE: The objective was to evaluate
      the safety and efficacy of highly purified 1000-cSt silicone oil injected by
      microdroplet serial puncture technique for the treatment of human
      immunodeficiency virus-associated lipoatrophy. METHODS: Data on 77 patients with
      a complete correction were analyzed to determine the number of treatments, amount
      of silicone, and time required to reach complete correction, relative to initial
      severity. RESULTS: The volume of silicone, number of treatments, and time
      required to reach a complete correction were directly related to initial severity
      of lipoatrophy (p < 0.0001). Supple, even facial contours were routinely
      restored, with all patients tolerating treatments well. No adverse events were
      noted. CONCLUSION: In this pilot trial, we have demonstrated that highly purified
      1000-cSt silicone oil is a safe and effective treatment option for human
      immunodeficiency virus facial lipoatrophy. Longer-term safety and efficacy in
      human immunodeficiency virus patients remain to be proven.

PMID- 15458524
TI  - Nonablative 1450-nm diode laser in the treatment of facial atrophic acne scars in
      type IV to V Asian skin: a prospective clinical study.
AB  - BACKGROUND: There is presently little published data on the clinical
      effectiveness of nonablative lasers in the treatment of atrophic acne scars and
      the safety of their use in patients with darker skin types. OBJECTIVE: This study
      aims to determine the clinical effectiveness and safety of the nonablative 1450
      nm diode laser with cryogen cooling spray in the treatment of facial atrophic
      acne scars in Type IV-V Asian skin. METHODS: This is a prospective non
      comparative open study. 4 to 6 laser treatment sessions were performed on
      patients with atrophic acne scars. Final clinical assessment was performed 6
      months after the last treatment. RESULTS: 57 patients were evaluated. Patient's
      self-assessment of scar improvement as compared with doctor's assessment was as
      follows: patients who completed 4 treatments (15.7% vs 6.6%), patients who
      completed 5 treatments (20% vs 7.9%) and patients those who completed 6
      treatments (17.3% vs 5.0%). Main side effects were mild to moderate pain during
      the procedure, transient erythema, and hyperpigmentation which occurred in 39% of
      treated patients. CONCLUSION: The nonablative 1450 nm diode laser may be
      effective in achieving mild to moderate gradual clinical improvement in the
      treatment of facial atrophic acne scars. The procedure is associated with minimal
      downtime and is safe for use in darker skin types IV and V.

PMID- 15458525
TI  - Combined nonablative skin rejuvenation with the 595- and 1450-nm lasers.
AB  - BACKGROUND: Histologic findings are not echoed in the visible effect in the
      epidermis after skin rejuvenation. SUBJECTS AND METHODS: Ten women (Group A)
      received five treatment sessions with a 595-nm pulsed dye laser immediately
      followed by a 1450-nm diode laser. Two other demographically similar groups of 10
      patients each, Groups B and C, were treated with the 595-nm pulsed dye laser or
      the 1450-nm diode laser alone, respectively. RESULTS: Good dermal collagen
      remodeling was observed in Group A. Overall better and faster results were seen
      in Group A. The 6-month clinical outcome was best in Group A followed by Group C
      and Group B. CONCLUSIONS: Wavelengths of 595 plus 1450 nm for skin rejuvenation
      produced good results with much higher patient satisfaction than those obtained
      with the 595- or 1450-nm wavelengths alone.

PMID- 15458526
TI  - The expression of p63 in actinic keratoses, seborrheic keratosis, and cutaneous
      squamous cell carcinomas.
AB  - BACKGROUND: p63 is a tumor suppressor that likely plays a role in the development
      of squamous cell carcinomas (SCCs) and possibly premalignant and benign skin
      tumors. Little data is available on its expression in these tumors. OBJECTIVE: To
      study the keratinocyte expression profile of p63 in 17 SCCs, 7 actinic keratoses,
      2 Bowens tumors, and 7 seborrheic keratoses. METHODS: Skin tumors specimens were
      stained with an antibody to p63. Quantitative and qualitative data was collected
      on the staining. RESULTS: There was a statistically significant increase in p63
      staining of SCCs when compared with normal. Seborrheic keratoses and actinic
      keratoses showed a trend towards increased expression in the basal layer compared
      with normal skin. The pattern of expression showed diffuse staining in SCCs. In
      actinic keratoses and seborrheic keratoses the pattern was most prominent in the
      basal layer. CONCLUSIONS: p63 expression is greater and different in SCCs when
      compared with normal skin, actinic keratoses, and seborrheic keratoses.
      Interestingly seborrheic keratoses and Bowens lesions showed expression that was
      mostly restricted to the basal layer, however significant diffuse staining was
      also noted. Our results support the notion that p63 plays a role in cell
      differentiation and tumorigenesis of skin tumors.

PMID- 15458527
TI  - Do vascular endothelial growth factor and basic fibroblast growth factor promote
      phenytoin's wound healing effect in rat? An immunohistochemical and
      histopathologic study.
AB  - BACKGROUND: This study was designed to determine the possible correlation between
      phenytoin and vascular endothelial growth factor and basic fibroblast growth
      factor in the wound healing process. METHODS: Sixty Wistar albino rats were
      divided into four groups, each containing 15 animals. The experimental groups
      received a daily phenytoin treatment (10 mg) for 3 or 7 days following 3-cm
      dorsal skin incisions on the midline; the control group incisions were treated
      with 0.5 mL of saline solution during the same time periods. After completion of
      treatments, all animals were killed, and skin tissue samples were obtained.
      RESULTS: Histopathologic examination of all groups revealed that there were
      significantly increased (p<0.05) amounts of fibroblasts, collagen deposition, and
      blood vessels in the phenytoin-treated groups when compared to the control
      groups. Although immunolocalization of vascular endothelial growth factor and
      basic fibroblast growth factor was weak in the 3-day phenytoin treatment groups,
      they were strongly expressed in the 7-day treatment group when compared to the
      control groups. CONCLUSION: The findings of this study demonstrate that the
      tissue alterations of the wound healing process could be accelerated by phenytoin
      and the potential local pathways of vascular endothelial growth factor and basic
      fibroblast growth factor.

PMID- 15458528
TI  - Mohs micrographic surgery for elliptical excision of skin tumors: a surgical and
      histologic study.
AB  - BACKGROUND: Elliptical excision is a standard form of treatment for cutaneous
      neoplasms, but routine pathologic sectioning results in incomplete histologic
      control of surgical margins. OBJECTIVE: The objective was to describe a technique
      of complete histologic margin control for tumors removed by excision as an
      ellipse. METHODS: A retrospective study of 100 consecutive nonmelanoma skin
      cancers of the head and neck removed using elliptical excisions with complete
      histologic margin control was performed. The technique is described and depicted
      in detail. RESULTS: Seventy-one tumors were removed in one excision, and 29
      required additional excisions for complete histologic tumor clearance. Linear
      repairs were used for 93 tumors. CONCLUSION: Elliptical excision, combined with
      our technique of complete histologic margin control, provides a simple,
      efficient, and effective method for surgical removal and repair of nonmelanoma
      skin cancers and provides an alternative variation of performing Mohs
      micrographic surgery for selected tumors.

PMID- 15458529
TI  - Micrometastasis of a sentinel lymph node in cutaneous melanoma is a significant
      prognostic factor for disease-free survival, distant-metastasis-free survival,
      and overall survival.
AB  - OBJECTIVE: Sentinel lymph node biopsy (SLNB) has been proposed as a minimally
      invasive procedure for the histopathologic staging of the regional lymph node
      basin. The aim of this work was to investigate the prognostic value of detection
      of micrometastasis by SLNB. METHODS: In the period from January 1996 to March
      2000, a sentinel lymph node (SLN) was identified in 283 patients at the
      Department Dermatology, University of Tuebingen. In the case of 38 patients
      (13.4%) histopathologic examination led to the detection of micrometastasis in at
      least one SLN. The median follow-up period was 29 months. RESULTS: Thirty-one of
      245 patients (12.7%) suffered a tumor recurrence following a negative SLNB, and
      19 of 38 patients (50%) following positive SLNB. In the case of disease-free
      survival the remaining significant independent prognostic factors of the
      multivariate analysis were tumor thickness (p=0.011), ulceration (p=0.026), and
      the detection of micrometastasis in SLNB (p=0.021). With respect to distant
      metastasis-free survival the significant independent prognostic factors of the
      multivariate analysis were tumor thickness (p=0.0022) and the SLNB results
      (p=0.0068). For overall survival the tumor thickness (p=0.013) and the SLNB
      results (p=0.034) were significant independent prognostic parameters in the
      multivariate analysis. CONCLUSION: The study examined patients with melanomas of
      all tumor thicknesses and SLNB for which the prognostic significance of SLNB was
      tested. Recurrences were more frequent in patients with a micrometastatic SLN.
      Patients with a negative SNLB are still at risk for tumor recurrence. The
      histopathologic result of SLNB is, after tumor thickness, the most significant
      prognostic factor for disease-free survival, distant-metastasis-free survival,
      and overall survival.

PMID- 15458530
TI  - Sentinel lymph node biopsy in patients with extramammary Paget's disease.
AB  - BACKGROUND: Patients with invasive extramammary Paget's disease appear to have a
      risk of regional lymph node metastasis. Despite the poor prognosis for patients
      with lymph node metastasis, management of extramammary Paget's disease without
      clinical evidence of involved nodes is controversial. OBJECTIVE: To evaluate the
      usefulness of sentinel lymph node biopsy, patients with extramammary Paget's
      disease underwent sentinel lymph node biopsy using preoperative
      lymphoscintigraphy and intraoperative patent blue dye injection with a handheld
      gamma-detecting probe. METHODS: Thirteen patients with primary genital
      extramammary Paget's disease were included in the study. Sentinel nodes
      identified were excised and examined by hematoxylin and eosin staining. All
      sentinel lymph nodes were also subjected to immunohistochemical staining for
      carcinoembryonic antigen, MUC1, cytokeratin 7, and gross cystic disease fluid
      protein-15. RESULTS: A total of 23 nodes were removed successfully. Tumor cells
      were detected in 4 nodes from four patients by hematoxylin and eosin staining. No
      additional lymph nodes were positive by immunohistochemistry. Three of the four
      sentinel-node-positive patients developed distant metastases. All nine patients
      without node involvement were free from disease during the follow-up period.
      CONCLUSION: Sentinel lymph node biopsy was safe and feasible method and may have
      an important role in the management of extramammary Paget's disease with
      clinically N0 status. To establish the optimal management of inguinal lymph nodes
      in extramammary Paget's disease, additional studies in large number of patients
      are needed.

PMID- 15458531
TI  - Nonsteroidal anti-inflammatory drug use in the prevention and treatment of
      squamous cell carcinoma.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs are widely reported to inhibit
      carcinogenesis. OBJECTIVE: The objective was to review the literature on
      nonsteroidal anti-inflammatory drugs in the prevention and treatment of cancer as
      it pertains to cutaneous squamous cell carcinoma. METHODS: We searched MEDLINE
      and performed a review of all published data on nonsteroidal anti-inflammatory
      drugs and cutaneous oncogenesis. RESULTS: In vitro and animal data strongly
      suggest a role for cyclooxygenase-2 in the formation of actinic keratoses and
      squamous cell carcinomas. Further observational studies and clinical trials are
      needed to assess their putative role in chemoprevention. CONCLUSIONS:
      Nonsteroidal anti-inflammatory drugs have activity against squamous cell
      carcinomas in vitro and in animal models, as well as in precursor lesions of
      squamous cell carcinomas. Human trials using selective cyclooxygenase-2
      inhibitors are currently in progress and should offer exciting information
      regarding the chemopreventative function of nonsteroidal anti-inflammatory drugs.

PMID- 15458532
TI  - Denial of illness: Basal cell carcinoma.

PMID- 15458533
TI  - A simple method of designing a bilobed flap using a triangle template.
AB  - BACKGROUND: The bilobed flap is useful for the reconstruction of skin defects in
      which the primary closure is difficult. Proper design is paramount to achieve
      excellent cosmetic results, but flap design often appears unnecessarily complex
      and difficult. OBJECTIVE: The objective was to discuss the geometry of the
      bilobed flap and describe a simple and practical method for constructing such
      flaps using a triangle template with emphasis on the pivot point. METHODS: A
      detailed description with diagrams and an illustrative case are presented to
      demonstrate the technique. RESULTS: A patient with a scalp defect was
      reconstructed with a triangle-template-designed bilobed flap with excellent
      postoperative results. CONCLUSION: This new method using a triangle template
      ensures proper placement of the pivot point and will enable practitioners to
      achieve superior outcomes.

PMID- 15458534
TI  - Adjacent-tissue skin grafts for reconstruction.
AB  - BACKGROUND: Large defects not easily repaired with local flaps and defects near
      anatomic free margins or crossing anatomic units present unique challenges for
      reconstruction. Cosmetic results of full-thickness skin grafts may appear
      unsatisfactory owing to differences in color, texture, and thickness between
      donor and recipient sites. OBJECTIVE: The objective was to describe a skin-graft
      reconstructive method that better approximates skin characteristics between donor
      and recipient sites while following other criteria to improve the final aesthetic
      and functional result. METHODS: Careful evaluation of the tissue surrounding a
      surgical defect determines tissue laxity available for skin grafting and whether
      the defect crosses anatomic units or may distort anatomic free margins or
      landmarks. Through partial closure of the large surgical defect, preferably
      within cosmetic units, a tricone is created large enough to graft the remaining
      wound. RESULTS: Creating smaller wounds within cosmetic units or subunits, there
      is less chance of distortion of nearby anatomic free margins or landmarks. Skin
      grafting is accomplished with tissue of similar color, texture, and thickness
      CONCLUSION: Adjacent-tissue skin grafts provide a suitable reconstruction option
      for surgical defects too large for simpler repair or defects crossing cosmetic
      units or near free margins. This procedure permits repair with a full-thickness
      skin graft of more similar skin characteristics to the recipient site.

PMID- 15458535
TI  - Lessons on dermoscopy: Dermoscopic pattern of hemosiderotic dermatofibroma.

PMID- 15458536
TI  - Subcision and 1320-nm Nd:YAG nonablative laser resurfacing for the treatment of
      acne scars: a simultaneous split-face single patient trial.
AB  - BACKGROUND: Many methods have been proposed for the treatment of acne scars with
      variable cosmetic results. Subcision has been successfully used, although
      complications often include a hyperpigmented and hypertrophic wound healing
      response. Nonablative skin resurfacing with a 1320-nm Nd:YAG laser has also been
      proposed; however, the results are generally inferior to those of more invasive
      modalities. OBJECTIVE: The objective was to improve on the results of 1320-nm
      Nd:YAG nonablative laser resurfacing by combining this treatment of acne scars
      with needle subcision. METHODS: A split-face trial was conducted in a patient
      with severe rolling and boxcar acne scars. One side of the face was treated with
      two sessions of subcision alone, spaced 6 weeks apart, whereas the other side was
      treated with two sessions of subcision spaced 6 weeks apart and 1320-nm Nd:YAG
      laser sessions every 2 weeks starting after the first subcision. At the
      conclusion of the split-face trial, the unlasered side was then treated with six
      biweekly sessions of 1320-nm Nd:YAG. RESULTS: Although the use of subcision
      resulted in an improvement of the patient's acne scars, the combination of
      subcision and nonablative laser resurfacing was superior in topography,
      pigmentation, and overall appearance of the acne scars. CONCLUSION: This case
      illustrates that dual treatment with subcision and 1320-nm Nd:YAG nonablative
      laser resurfacing is a well-tolerated and highly effective regimen for the
      improvement of facial acne scars, compared to subcision alone.

PMID- 15458537
TI  - Extramammary Paget's disease presenting on the face.
AB  - BACKGROUND: Extramammary Paget's disease is a rare neoplasm primarily affecting
      apocrine gland bearing skin. Although primarily affecting the anogenital area,
      the tumor also rarely appears in nonapocrine bearing skin and is referred as
      ectopic extramammary Paget's disease. OBJECTIVE: To our knowledge, we present
      only the second case of ectopic extramammary Paget's disease appearing on the
      face. METHODS: Using Mohs micrographic surgery, a rare case of ectopic
      extramammary Paget's disease on the face was treated in three stages. RESULTS: At
      5 months there was no evidence of recurrence. CONCLUSION: Ectopic extramammary
      Paget's disease is a rare disease that can be effectively treated with Mohs
      micrographic surgery.

PMID- 15458538
TI  - Angiokeratoma circumscriptum.
AB  - Angiokeratoma circumscriptum is one of five types in the group of the
      angiokeratomas. These lesions are usually present at birth and are not related
      with systemic diseases. Angiokeratoma circumscriptums are hyperkeratotic papules
      or nodules occurring frequently unilaterally on the leg. These lesions are very
      rare and very few cases have been reported since its first description. It is of
      particular clinical importance because of its morphologic similarities to
      malignant skin tumors such as malignant melanoma or pigmented basal cell
      carcinoma. Therefore, this rare but significant lesion must be recognized by
      physician and surgeons who manage skin tumors.

PMID- 15458539
TI  - Angiolymphoid hyperplasia with eosinophilia associated to a squamous cell
      carcinoma of the ear.
AB  - BACKGROUND: Angiolymphoid hyperplasia with eosinophilia is a benign vascular
      proliferation that usually affects the head and neck region. METHOD: An 89-year
      old man who had a squamous cell carcinoma on the posterior aspect of one ear
      developed lesions of angiolymphoid hyperplasia with eosinophilia on the anterior
      aspect of the same ear. RESULTS: After surgical treatment of the malignant
      neoplasm, the lesions of angiolymphoid hyperplasia with eosinophilia disappeared
      spontaneously. CONCLUSIONS: Damage to the vasculature of the ear by the malignant
      neoplasm or the release of angiogenic factors by the same neoplasm is a plausible
      explanation for the development and eventual resolution of the vascular
      proliferation.

PMID- 15458540
TI  - Abstracts of the 30th European Congress of Cytology. October 12-15, 2004. Athens,
      Greece.

PMID- 15458541
TI  - Fructose overload modifies vascular morphology and prostaglandin production in
      rats.
AB  - 1. A fructose (Fru)-enriched diet induces a mild increase in blood pressure
      associated with hyperglycaemia, hypertriglyceridaemia, and insulin resistance,
      resembling the human 'syndrome X', being an useful model to study hypertension
      and type 2 diabetes. 2. A sustained elevation of blood pressure is associated
      with cardiovascular structural modifications such as left ventricular hypertrophy
      and increased wall thickness:lumen diameter ratio in blood vessels. 3.
      Prostanoids (PR), metabolites of arachidonic acid through the cyclooxygenase
      pathway, include vasoactive substances synthesized and released by the vessel
      walls. 4. The aim of the present study was to analyse, in Fru-treated rats: (i)
      the morphology of mesenteric vessels and; (ii) the PR production in aorta and
      mesenteric vessels, in order to assess whether these parameters are related with
      the haemodynamic alterations observed in this experimental model. 5. Blood
      pressure, glycaemia and triglyceridaemia, were significantly elevated in both (4
      and 22 weeks) Fru-treated groups. Meanwhile body and heart weight as well as
      insulinaemia were similar between experimental animals and controls. 6. The
      mesenteric vessels of Fru-treated rats (22 weeks) showed an increased thickness
      and area of the media when compared with the controls; meanwhile, the lumen
      diameter was similar in both groups. 7. The Fru treatment for 4 weeks did not
      modify PR production in aorta, whereas in the mesenteric bed it diminished
      prostaglandin (PG) E(2) release significantly compared with the controls.
      However, in the group treated for 22 weeks, Fru reduced PGI(2) production in the
      aorta, as assessed by 6-keto-PGF(1)alpha measurements. Meanwhile, in the
      mesenteric bed, the chronic Fru treatment decreased PGE(2) release but, rather
      surprisingly, increased the output of PGI(2) when compared with its corresponding
      controls. 8. In conclusion, the present study shows the existence of an
      alteration in the morphology of mesenteric vessels in Fru-treated rats, which
      could be related to an increase in peripheral resistance and the consequent mild
      hypertension observed in this model. However, a diminished release of vasodilator
      PRs, such as PGE(2) in mesenteric vessels at 4 and 22 weeks and PGI(2) in aorta
      at 22 weeks could further impair the vessel response. The increase in PGI(2)
      observed in the chronic group in mesenteric vessels could be attributed to a
      compensatory mechanism.

PMID- 15458542
TI  - Evidence showing that beta-adrenoceptor subtype responsible for the relaxation
      induced by isoprenaline is principally beta 2 but not beta 1 in guinea-pig
      tracheal smooth muscle.
AB  - 1. The present study was carried out to pharmacologically identify the beta
      adrenoceptor subtype that mediates isoprenaline-elicited relaxation in the
      isolated guinea-pig tracheal smooth muscle, to answer the question whether it is
      beta(1)- or beta(2)-subtype? 2. Isoprenaline as well as salbutamol, a well-known
      beta(2)-selective adrenoceptor agonist, produced a concentration-dependent
      relaxation with a pD(2) value of 8.12 vs. 7.54 for salbutamol. 3. Isoprenaline
      elicited relaxation was not affected by beta(1)-selective antagonists, atenolol
      and CGP-20,712A, within the concentration ranges supposed to antagonize beta(1)
      subtype: atenolol, < or =10(-6) M; CGP-20,712A, < or =10(-8) M. 4. By contrast,
      the concentration-response curves for isoprenaline as well as salbutamol were
      shifted rightwards in a competitive fashion by atenolol at the concentrations >
      or =3 x 10(-6) M. However, pA(2) values of atenolol against isoprenaline (5.86)
      and salbutamol (5.71) were consistent with the value corresponding to beta(2)-
      but not to beta(1)-subtype (around 7.00), and these values were not significantly
      different from each other. 5. Competitive antagonism of the relaxations to
      isoprenaline and salbutamol were also obtained with beta(2)-selective
      antagonists, butoxamine and ICI-118,551. Against isoprenaline and salbutamol, the
      pA(2) values of butoxamine (6.51 vs. 6.81) and ICI-118,551 (8.83 vs. 8.90) were
      substantially identical. Thus the primary mediation of beta(2)-receptor in the
      relaxations was strongly supported. 6. The present findings provide evidence that
      the beta-adrenoceptor which mediates isoprenaline-elicited relaxation of guinea
      pig tracheal smooth muscle is essentially beta(2)- but not beta(1)-subtype. The
      present study also indicates the importance of using multiple receptor
      antagonists with different pA(2) values to pharmacologically identify the
      responsible receptor subtype in smooth muscle mechanical responses.

PMID- 15458543
TI  - Functional alterations of mesenteric vascular bed, vas deferens and intestinal
      tracts in a rat hindlimb unloading model of microgravity.
AB  - 1. Prolonged bed rest or exposure to microgravity may cause several alterations
      in autonomic nervous system response (ANSR). 2. Hindlimb unloading (HU) rats were
      used as an animal model of simulated microgravity to investigate ANSR changes.
      The experiments were carried out to investigate the effects of simulated
      microgravity on the autonomic nervous response of the perfused mesenteric
      vascular bed (MVB), vas deferens and the colon and duodenum from 2-week HU rats.
      3. In MVB preparations of HU rats, the frequency-dependent increases in perfusion
      pressure with perivascular nerve stimulation (PNS; 8-40 Hz) were inhibited,
      whereas the noradrenaline (NA) concentration-dependent (1-100 microM) perfusion
      pressure increases were potentiated. The latter most probably reflected up
      regulation of alpha-adrenergic receptor function. Relaxant responses of NA
      precontracted MVB to PNS (4-30 Hz) or isoprenaline were not different between
      control and HU preparations, while vasodilation induced by the endothelial
      agonist ACh was reduced. 4. Transmural stimulation (2-40 Hz) induced frequency
      dependent twitches of the vas deferens which were reduced in vas deferens of HU
      rats, while the sensitivity to NA-induced contraction was significantly
      increased. 5. In the gastroenteric system of HU rat, direct contractile responses
      to carbachol or tachykinin as well as relaxant or contractile responses to
      nervous stimulation appeared unchanged both in the proximal colon rings and in
      duodenal longitudinal strips. 6. In conclusion, HU treatment affects peripheral
      tissues in which the main contractile mediators are the adrenergic ones such as
      resistance vessels and vas deferens, probably by reducing the release of
      neuromediator. This study validates NA signalling impairment as a widespread
      process in microgravity, which may most dramatically result in the clinical
      phenotype of orthostatic intolerance.

PMID- 15458544
TI  - In vitro maturation of fresh and frozen-thawed mouse round spermatids.
AB  - Both initiation and maintenance of spermatogenesis are hormonally regulated by
      follicle stimulating hormone (rFSH) and testosterone. Co-culture systems also
      have important roles in the maintenance of spermatogenic cells. In this study,
      the effects of FSH and testosterone, co-culture system with Vero cells and co
      culture supplemented with the hormones for maturation of frozen-thawed spermatids
      were determined. Testicular cells were suspended from the testis of National
      Medical Research Institute (NMRI) male mice and divided into two parts. The first
      aliquot of suspension was allocated for using as fresh and the rest was quickly
      cryopreserved. The frozen specimens were thawed and washed using Dulbecco
      modified Eagle's minimum essential medium (DMEM) medium. The fresh specimens were
      cultured in four groups: control (cultured on DMEM with 10% FBS), hormone
      (cultured on a medium supplemented with rFSH and testosterone), co-culture
      (cultured on Vero cells) and co-culture + hormone (cultured on Vero cells
      combined with rFSH and testosterone). The frozen-thawed specimens were cultured
      accordingly. The number of spermatids was recorded daily and the survival rates
      of each group were evaluated using Trypan blue test. The results showed that the
      number of the elongating spermatids was increased during the first day of the
      culture of fresh hormone, co-culture and co-culture + hormone groups. Viability
      rates of all kinds of the spermatid reduced during the 96 h of culturing. Our
      findings showed that the addition of hormone could support cell viability better
      than the co-culture. They also confirmed that the fresh round spermatid cells can
      progress into elongating and elongated spermatid only within the first 2 days of
      the culture in hormone, co-culture and co-culture + hormone groups. In the frozen
      thawed specimens no extra significant increase in the number of cells was
      observed.

PMID- 15458545
TI  - Effects of testosterone and vitamin E on the antioxidant system in rabbit testis.
AB  - The aim of the study was to investigate the effects of testosterone propionate
      and vitamin E on the antioxidant system in the testis. Thirty-two male New
      Zealand White rabbits were randomly divided into four groups. The first group was
      used as control. The second group was injected with testosterone propionate, the
      third group vitamin E and the fourth group vitamin E and testosterone propionate
      combination. All treatments were carried out during 6 weeks and oxidative
      parameters were evaluated in homogenized testicular tissue. The levels of vitamin
      E and the activity of glutathione peroxidase were lower (P < 0.05) in the
      testosterone group than in controls. However, vitamin C and malondialdehyde
      levels were higher (P < 0.05) in this group than in controls. The levels of
      reduced glutathione, beta-carotene, vitamin C and E increased, but
      malondialdehyde levels decreased in the vitamin E group, when compared with
      controls (P < 0.05). Vitamin E and beta-carotene levels were significantly higher
      (P < 0.05) in the combination group than in testosterone group. However, MDA
      levels were lower (P < 0.05) in combination group than in the testosterone group.
      In conclusion, administration of testosterone propionate led to a significant
      elevation of oxidative stress. Vitamin E is quite an effective antioxidant which
      protects rabbit testis against lipid peroxidation, and, testosterone-induced
      lipid peroxidation could be improved by additional vitamin E treatment.

PMID- 15458546
TI  - Bacterial risk and sperm cryopreservation.
AB  - Prior to sperm cryopreservation, French guidelines only recommend viral screening
      for serological status towards human immunodeficiency virus, hepatitis B and C
      viruses and Treponema palidum. The probability of semen infection by other
      bacterial pathogens is not taken into consideration by the current
      recommendations. The objective of the present study was to evaluate this risk and
      a strategy to reduce it prospectively. Ninety-six patients consulting for sperm
      cryopreservation underwent a semen culture simultaneously to cryopreservation.
      The patients were classified into three groups following semen culture results:
      negative culture (group 1, 77/96, 80.2%), positive culture with saprophytic
      agents (group 2, 9/96, 9.4%) and positive culture with pathogen agents (group 3,
      10/96, 10.4%). For six patients of the latter group showing a genital infection
      with Ureaplasma urealyticum, a discontinuous gradient selection performed on the
      cryopreserved sample was efficient to discard bacteria. These data emphasize the
      usefulness to cultivate semen simultaneously to cryopreservation and demonstrate
      the ability to remove some microbial agents from semen before its use in assisted
      reproductive techniques.

PMID- 15458547
TI  - Localization of binding sites of naturally occurring antisperm antibodies on
      human spermatozoa by immunofluorescence.
AB  - Antisperm antibodies (ASA) may affect sperm motility, acrosome reaction, sperm
      penetration of cervical mucus, binding to the zona pellucida, and sperm-egg
      fusion. We investigated the localization of ASA of infertile men or men after
      vasectomy bound on the sperm surface using an immunofluorescence method. Binding
      occurred in the acrosomal region, midpiece, and tail. Most of the ASA in both
      groups of patients bound to the midpiece alone or in combination with other
      regions of spermatozoa. Only few ASA samples showed binding to all the three
      sperm regions. A combination of binding to the acrosomal region and to the
      midpiece was never observed. In infertile patients with ASA, the binding site was
      compared with sperm parameters. ASA binding to the sperm head influenced the
      acrosome reaction. Binding of ASA on tail and/or midpiece was not associated with
      a significant alteration of viability and motility. Immunofluorescence appears to
      be a valuable tool in the diagnosis of immune infertility, in particular when
      impairment of the acrosome activity is suggested.

PMID- 15458548
TI  - Pre-decondensed sperm head injections into female pronuclei result in chromosomal
      mingling, zygotic cleavage, and adequate embryonic and fetal development up to
      delivery of healthy offspring: a novel method of assisted syngamy.
AB  - Investigation of the developmental potential post-injection of a pre-decondensed
      or non-pre-decondensed sperm head into the female pronucleus of a pre-activated
      oocyte. Rat pre-activated oocytes were treated with intrapronuclear pre
      decondensed sperm head injections (IPSHI) (n = 133) or intrapronuclear non-pre
      decondensed sperm head injections (INPSHI) (n = 138). All injected oocytes were
      transferred to pseudopregnant female recipients. Rat IPSHI techniques resulted in
      the delivery of five healthy offspring. Rat INPSHI techniques did not result in
      any pregnancies. Rat IPSHI techniques can result in delivery of healthy
      offspring. Successful performance of human IPSHI techniques might serve as a
      novel method to manage cases of intracytoplasmic sperm injection failure due to
      lack of development of male pronucleus or due to failure in pronuclei fusion.

PMID- 15458549
TI  - Nicotinic infertility: assessing DNA and plasma membrane integrity of human
      spermatozoa.
AB  - Infertility remains a major problem in society, with recent data suggesting its
      presence in one of four couples. The objective of the present study was to
      evaluate the impact of nicotine (0.25, 0.5 and 0.75 mm), as a major component of
      cigarette smoke, in vitro, on sperm membrane [by spermatocrit and
      lipoperoxidation (LPO) tests], DNA integrity (by Comet assay), and viability of
      spermatozoa (by eosin staining) from normozoospermic men. Sperm samples were
      washed and diluted with phosphate-buffered saline. A drop in spermatocrit values
      and an increase in thiobarbituric acid-reactive substances/LPO rate was observed
      with the addition of nicotine, predominantly at a concentration of 0.75 mm,
      indicating a deleterious effect of nicotine on sperm membrane intactness. There
      was also a strong negative correlation between LPO rate and percentage viable
      sperm cell (r = -0.990). Data obtained from Comet assay technique revealed that
      nicotine could induce double-stranded DNA breaks (11% in 0.75 mm concentration)
      in the sperm nuclei. The value of r between LPO rate and percentage Comets was
      found to be +0.976. Taken together, nicotine proved to be a potential oxidant
      agent in the category of environmental factors to the integrity of sperm plasma
      membrane and DNA.

PMID- 15458550
TI  - Laparoscopy-assisted pelvi-scrotal vasovasostomy.
AB  - Iatrogenic obstruction of the vas deferens within the inguinal canal can be
      managed by direct on-site vasovasostomy. However, in cases with large defect of
      the vas, the anastomosis may be under tension. Dissecting through the site of a
      previous hernia repair is tedious, and may lead to recurrence of the hernia. The
      present work reports an, first of a kind, alternative technique that avoids the
      latter drawbacks. Fifteen cases were operated upon. Under laparoscopic vision,
      the pelvic vas was dissected and the lateral-most end was clipped, cut and
      extruded from the abdomen through a port in the external inguinal ring. End-to
      end vasovasostomy and microsurgical anastomosis for the vasal vessels were
      performed, bridging the retrieved stump of the pelvic vas with the scrotal vas.
      There were positive results in the form of sperm count ranging from 1.5 to 15
      million ml(-1), an average of 7.25 (SD 5.44) in nine of 15 cases (60%), within
      the first 6 months following surgery. "Pelvi-scrotal vasovasostomy" can be
      offered as a cost-effective and successful alternative or supplement to
      intracytoplasmic sperm injection, for cases with iatrogenic large defects of the
      vas deferens within the inguinal canal.

PMID- 15458551
TI  - Alpha-glucosidase in the human epididymis: topographic distribution and clinical
      application.
AB  - Alpha-glucosidase activity (EC.3.2.1.20) is present in human seminal plasma, and
      the neutral form of the enzyme originates almost exclusively from the epididymis.
      In this study, the specific immunocytochemical location of alpha-glucosidase in
      the human epididymis was evaluated using a polyclonal antibody. Furthermore, a
      spectrophotometric assay was employed to assess epididymal obstruction in
      infertile patients. The enzymatic activity of alpha-glucosidase free of prostate
      isoform (AGFPI) was determined spectrophotometrically at 405 nm. According to
      AGFPI activity, patients with leucocytospermia, oligozoospermia and azoospermia
      were recorded as having normal values or low values indicating epididymal
      obstruction. Specific immunochemistry staining was demonstrated in the
      cytoplasmic cells at the epithelial level, in the transition area and in the
      efferent ducts. The values of the three groups and the control were as follows
      (mean +/- SEM): normozoospermia (control): 20.2 +/- 1.4 mU ml(-1); azoospermia:
      normal value: 17.6 +/- 2.2 mU ml(-1), low value: 7.4 +/- 1.8 mU ml(-1);
      oligozoospermia: normal value: 22.3 +/- 2.5 mU ml(-1), low value: 7.3 +/- 0.7 mU
      ml(-1); leucocytospermia: increase value: 38.9 +/- 3.7 mU ml(-1), low value: 11.1
      +/-1.3 mU ml(-1). This study suggests that determination of alpha-glucosidase
      might be helpful to evaluate functions of the epididymis and particularly to
      exclude epididymal obstruction.

PMID- 15458552
TI  - Evaluation of chromatin integrity in human sperm using acridine orange staining
      with different fixatives and after cryopreservation.
AB  - Staining of cells with acridine orange (AO) has been widely accepted as a
      predictor of DNA damage in many cell types. Because of variability of protocols
      used in previous studies, the AO staining technique has not been widely accepted
      as a screening test to predict DNA damage in human sperm. In order to further
      validate the use of AO staining, sperm were evaluated using numerous variations
      in the staining protocol. This study also elucidated the effects of
      cryopreservation on sperm DNA. Sperm fixation in Carnoy's solution showed
      significantly (P < 0.05) more DNA damage (29.9 +/- 4.5%) than 2% glutaraldehyde
      (14.4 +/- 2.1%), 4% paraformaldehyde (5.5 +/- 1.7%), no fixation (15.8 +/- 4.3%)
      but did not differ from Diff Quik solution (19.2 +/- 5.8%). No difference was
      observed for sperm DNA damage assessment using a 0.2 m (15.5 +/- 3.2%) or 0.3 m
      (14.9 +/- 3.3%) concentration of Na(2)HPO(4).7H(2)O in the AO staining solution.
      Frozen-thawed semen samples showed increased damage to sperm DNA under both
      Carnoy's (fresh: 10.9 +/- 1.3%; frozen: 30.8 +/- 2.9%; P < 0.05) and Diff Quik
      fixation (fresh: 6.2 +/- 0.8; frozen: 17.1 +/- 2.5%P < 0.05). Present data also
      showed that spermatozoa from some individuals are more prone to DNA damage after
      freezing and thawing procedures than others. In conclusion, Carnoy's fixative
      provides a better predictive value for DNA damage to sperm using AO staining.
      Additionally, cryopreservation increased damage to the sperm DNA.

PMID- 15458553
TI  - Immunolocalization of heat shock protein 70 in bovine spermatozoa.
AB  - Heat shock protein 70 (HSP70) is part of a superfamily of molecular chaperones,
      which protect cells from chemical and heat shock. The objectives of this study
      were to determine the presence of HSP70 in bovine spermatozoa and its subcellular
      localization during different stages of spermatogenesis. Analysis of sperm
      proteins by Western blotting using a monoclonal antibody to the inducible form of
      HSP70 revealed a single immunoreactive band with an estimated molecular weight of
      70 kDa in samples from 18 of 18 bulls. Using immunofluorescence microscopy and
      the same antibody, HSP70 was localized to the cytoplasm of prophase spermatocytes
      and elongating spermatids, to cytoplasmic droplets of caput epididymal
      spermatozoa, and to cytoplasmic droplets, acrosome, post-acrosomal region and
      middle piece of corpus and cauda epididymal spermatozoa. The pattern of
      distribution changed in freshly ejaculated spermatozoa as HSP70 was detected on
      the acrosome only. During capacitation and acrosome reaction, HSP70 was once
      again redistributed, and was localized to the equatorial segment, post-acrosomal
      region and middle piece. Thus, HSP70 is present in the spermatozoa of mature
      bulls and redistribution of the protein occurs during capacitation and the
      acrosome reaction.

PMID- 15458555
TI  - New developments in perinatal mental health.

PMID- 15458556
TI  - On phenomenology and classification of hoarding: a review.
AB  - OBJECTIVE: Hoarding is a behavioural abnormity characterized by the excessive
      collection of poorly usable objects. It is described mainly in association with
      obsessive-compulsive disorders (OCDs) and in geriatric populations. Yet the
      literature on the phenomenon is heterogeneous and the notion obviously lacks a
      consistent definition. This review attempts to describe the psychopathological
      and clinical spectrum of hoarding and may contribute to clarify its
      classification. METHOD: Systematic review and discussion of the literature on
      hoarding. RESULTS: Hoarding is a complex behavioural phenomenon associated with
      different mental disorders. The psychopathological structure is variously
      composed of elements of OCDs, impulse-control disorders, and ritualistic
      behaviour. Severe self-neglect is a possible consequence of hoarding. CONCLUSION:
      Without further specifications the term hoarding is of limited heuristic value
      and cannot guide therapeutic interventions satisfactorily. The condition needs to
      be evaluated carefully in every particular case in relation to the aforementioned
      psychopathological concepts.

PMID- 15458557
TI  - Identifying women at-risk for postpartum depression in the immediate postpartum
      period.
AB  - OBJECTIVE: To develop a multifactorial predictive model of depressive
      symptomatology in the first week postpartum in order to assist in targeted
      screening procedures. METHOD: As part of a longitudinal study, a population-based
      sample of 594 mothers in a health region near Vancouver, British Columbia
      completed a mailed questionnaire at 1-week postpartum that included diverse risk
      factors from the following domains: sociodemographic, biological, pregnancy
      related, life stressors, social support, obstetric and adjustment to motherhood.
      Following univariate analysis, sequential regression analysis was completed to
      develop a multifactorial predictive model. RESULTS: In the multivariate model,
      the factors predictive of depressive symptomatology at 1-week postpartum included
      immigration within the last 5 years, history of depression independent of
      childbirth, diagnosis of pregnancy-induced hypertension, vulnerable personality
      style, stressful life events, lack of perceived support, lack of readiness for
      hospital discharge and dissatisfaction with infant feeding method. CONCLUSION:
      The findings suggest that several risk factors for depressive symptomatology in
      the immediate postpartum period are consistent with previously identified factors
      but other factors such as recent immigrant status, feeling unready for hospital
      discharge, dissatisfaction with their infant feeding method, and pregnancy
      induced hypertension should also be examined.

PMID- 15458558
TI  - Predictors of parenting outcome in women with psychotic disorders discharged from
      mother and baby units.
AB  - OBJECTIVE: To compare the social and clinical characteristics of mothers with
      psychotic disorders with parenting difficulties, with mothers with no significant
      parenting problems. METHOD: Descriptive and case-control study. RESULTS: Over
      half of the women with psychotic disorders admitted to psychiatric mother and
      baby units had a good outcome at the time of discharge--70% did not need social
      services supervision, and had no significant parenting problem as judged by
      clinical staff. Diagnosis was independently associated with all measures of poor
      parenting; compared with a diagnosis of psychotic depression, a diagnosis of
      schizophrenia was highly significantly associated with social services
      supervision [adjusted odds ratio (OR) 25.7; 95% CI 5.97, 111.05], and staff rated
      problems with emotional responsiveness (adjusted OR 3.39;95% CI 1.42, 8.08),
      practical baby care (adjusted OR 6.07; 95% CI 2.12, 17.39), and perceived risk of
      harm to baby (adjusted OR 7.81; 95% CI. 2, 30.53). Low social class and
      psychiatric illness in the partner were also significantly associated with poor
      parenting outcomes, including social services supervision (adjusted OR 3.88; 95%
      CI 2.07, 7.25 and 4.23; 95% CI 2.1, 8.55, respectively). CONCLUSIONS: Although
      these associations do not demonstrate causality, these findings suggest
      preventative interventions targeting socio-economic difficulties, early treatment
      of psychosis, and detection and treatment of psychiatric problems in the partner
      may be helpful in improving parenting outcomes in these vulnerable families.

PMID- 15458559
TI  - Early maternal stress and health behaviours and offspring expression of psychosis
      in adolescence.
AB  - OBJECTIVE: It has been suggested that influences operating early in life may
      affect the risk of postpubertal psychosis outcomes. This hypothesis was tested
      using a broad outcome of psychotic symptoms expressed in adolescence (prevalence:
      15.6%). METHOD: Findings are based on a longitudinal, population-based cohort
      study of 963 adolescents aged 15-20 years and their parents in the area of
      Munich, Germany. Trained psychologists assessed adolescents with the Munich
      Composite International Diagnostic Interview. Independently, direct diagnostic
      interviews were conducted with the parents. RESULTS: A range of medical
      complications of pregnancy and delivery, including lower birth weight, were not
      associated with the psychosis outcome. However, a number of maternal health
      behaviours and experiences did show associations, independent of confounders.
      CONCLUSION: Not maternally reported medical complications of pregnancy and
      delivery, but maternal prenatal health behaviours predicted expression of
      psychosis along a continuum in adolescence. This effect may either be direct or
      constitute a proxy for later postnatal maternal behaviours associated with
      psychosis risk in the offspring.

PMID- 15458560
TI  - Long-term outcome of offspring after maternal severe puerperal disorder.
AB  - OBJECTIVE: To study adult mental health in offspring of mothers who experienced
      severe puerperal disorder. METHOD: Mothers, followed up a mean of 23 years after
      puerperal disorder requiring hospitalization, were interviewed regarding adult
      psychiatric illness, childhood neurotic symptoms and conduct problems of 48
      offspring of the index episode and 62 additional siblings. RESULTS: In these
      predominantly young adults the lifetime rate of ICD-10 adult psychiatric illness
      was 26%, and was higher in offspring of puerperal episodes (35% vs. 15%, P =
      0.07). There were also high rates of childhood symptoms and problems. CONCLUSION:
      There are high lifetime rates of adult psychiatric illness in young adult
      offspring of mothers with puerperal disorder, which are likely to increase
      further with time, and warrant special attention.

PMID- 15458561
TI  - Prevalence of bipolar disorder in the general population: a Reappraisal Study of
      the Netherlands Mental Health Survey and Incidence Study.
AB  - OBJECTIVE: The Netherlands Mental Health Survey and Incidence Study (NEMESIS) is
      a Dutch population study using a fully structured interview (Composite
      International Diagnostic Interview, CIDI), administered by trained interviewers.
      Based on all three assessments of NEMESIS, 2.4% of the respondents were
      identified with lifetime bipolar disorder (DSM-III-R). The primary aim of the
      study was to estimate the prevalence of bipolar disorder in the same population
      based on a semistructured interview administered by clinicians. METHOD: Seventy
      four persons identified with a lifetime CIDI/DSM-III-R bipolar disorder and 40
      persons with a major depressive disorder (MDD) were reinterviewed with the
      Structured Clinical Interview for DSM (SCID). RESULTS: Based on the SCID, 30 of
      74 respondents with a CIDI/DSM-III-R bipolar disorder and eight of 40 respondents
      with MDD met DSM-IV criteria for bipolar disorder or cyclothymia, corresponding
      with an adjusted lifetime prevalence in these groups of 1% (95% CI: 0.7-1.3%) and
      4.2% (95% CI: 1.6-6.9%) respectively. CONCLUSION: Compared with the SCID, the
      CIDI on the one hand overdiagnoses bipolar disorder but on the other hand
      underdiagnoses bipolar disorder.

PMID- 15458562
TI  - The societal costs and quality of life of patients suffering from bipolar
      disorder in the Netherlands.
AB  - OBJECTIVE: To assess the societal costs and quality of life of patients suffering
      from bipolar disorder in the Netherlands. METHOD: Forty persons with a lifetime
      diagnosis of bipolar disorder (SCID/DSM-IV) and representative for the Dutch
      general population were interviewed to collect data on direct (use of medical
      resources) and indirect (productivity losses because of absence from work and
      reduced efficiency at work) costs of illness. Respondents' quality of life was
      also assessed. Prevalence (5.2%) of bipolar disorder was used to estimate total
      costs. RESULTS: Total costs of bipolar disorder were estimated at US 1.83 billion
      dollars (total direct costs = US 454 million dollars; total indirect costs = US
      1.37 billion dollars). Participants' quality-of-life scores were lower than those
      of the general population. CONCLUSION: The societal costs form patients suffering
      of bipolar disorder in the Netherlands were high, especially the indirect costs
      because of absence from work. The quality of life of bipolar patients was lower
      than the general population.

PMID- 15458563
TI  - Early detection of relapse in panic disorder.
AB  - OBJECTIVE: To explore predictive models of relapsing based on change in symptoms
      at a time when panic disorder patients are still in remission following
      discontinuation of antidepressants. METHOD: Forty-seven subjects, who were
      randomized to double-blind placebo and who had valid data at four time points:
      pretreatment, randomization to placebo substitution, an assessment on placebo
      prior to the last assessment or relapse and their last assessment (relapsers n =
      15, non-relapsers n = 32) were studied using descriptive, growth curve analysis
      and logistic regression methodologies. RESULTS: Measures of generalized anxiety,
      fearfulness and disability at work and at home were better predictors of relapse
      than measures of panic and anxiety sensitivity. Logistic regression models using
      any one of these four general variables and its linear change correctly predicted
      relapse for 78.7-84.4% of the study subjects. CONCLUSION: It is possible to
      gauge, with a fair degree of accuracy, the probability of relapsing in panic
      disorder patients who have discontinued serotonergic antidepressants 2 months
      prior to the return of panic.

PMID- 15458565
TI  - Utilization of a ts-sacB selection system for the generation of a Mycobacterium
      avium serovar-8 specific glycopeptidolipid allelic exchange mutant.
AB  - BACKGROUND: Mycobacterium avium are ubiquitous environmental organisms and a
      cause of disseminated infection in patients with end-stage AIDS. The
      glycopeptidolipids (GPL) of M. avium are proposed to participate in the
      pathogenesis of this organism, however, establishment of a clear role for GPL in
      disease production has been limited by the inability to genetically manipulate M.
      avium. METHODS: To be able to study the role of the GPL in M. avium pathogenesis,
      a ts-sacB selection system, not previously used in M. avium, was employed as a
      means to achieve homologous recombination for the rhamnosyltransferase (rtfA)
      gene of a pathogenic serovar 8 strain of M. avium to prevent addition of serovar
      specific sugars to rhamnose of the fatty acyl-peptide backbone of GPL. The
      genotype of the resultant rtfA mutant was confirmed by polymerase chain reaction
      and southern hybridization. Disruption in the proximal sugar of the haptenic
      oligosaccharide resulted in the loss of serovar specific GPL with no change in
      the pattern of non-serovar specific GPL moieties as shown by thin layer
      chromatography and gas chromatography/mass spectrometry. Complementation of wild
      type (wt) rtfA in trans through an integrative plasmid restored serovar-8
      specific GPL expression identical to wt serovar 8 parent strain. RESULTS: In this
      study, we affirm our results that rtfA encodes an enzyme responsible for the
      transfer of Rha to 6d-Tal and provide evidence of a second allelic exchange
      mutagenesis system suitable for M. avium. CONCLUSION: We report the second
      allelic exchange system for M. avium utilizing ts-sacB as double-negative and
      xylE as positive counter-selection markers, respectively. This system of allelic
      exchange would be especially useful for M. avium strains that demonstrate
      significant isoniazid (INH) resistance despite transformation with katG. Through
      the construction of mutants in GPL or other mycobacterial components, their roles
      in M. avium pathogenesis, biosynthesis, or drug resistance can be studied in a
      consistent manner.

PMID- 15458566
TI  - Is nebulized saline a placebo in COPD?
AB  - BACKGROUND: Many trials of nebulized therapy have used nebulized saline as a
      "placebo". However, nebulized isotonic saline is sometimes used to assist sputum
      expectoration and relieve breathlessness in COPD patients. We designed this study
      to establish if nebulized saline had a placebo effect or a clinical effect.
      METHODS: 40 patients were studied following hospital admission for exacerbated
      COPD (mean FEV1 30% predicted). Patients were randomised to single-blind
      administration of either 4 mls of nebulized isotonic saline using an efficient
      nebulizer (active group n = 20) or an inefficient nebulizer (placebo group n =
      20). Spirometry and subjective breathlessness scores (Modified Likert Scale) were
      measured before nebulized treatment and 10 minutes after treatment. RESULTS:
      There was no significant change in FEV1 after active or placebo nebulized saline
      treatment. Patients reported a 4% improvement in mean breathlessness score
      following placebo (Wilcoxon test; p = 0.37) compared with 23% improvement
      following active nebulized saline (p = 0.0001). 65% of patients given active
      nebulized saline but only 5% of the placebo group reported that mucus
      expectoration was easier after the treatment. CONCLUSIONS: This study lends
      support to the current use of nebulized saline to relieve breathlessness
      (possibly by facilitating sputum clearance) in COPD patients. Lung function was
      not affected. Nebulized saline can therefore be used as a placebo in
      bronchodilator studies involving COPD patients but it cannot be used as a placebo
      in trials assessing symptom relief.

PMID- 15458567
TI  - Targeting smoking cessation to high prevalence communities: outcomes from a pilot
      intervention for gay men.
AB  - BACKGROUND: Cigarette smoking prevalence among gay men is twice that of
      population levels. A pilot community-level intervention was developed and
      evaluated aiming to meet UK Government cessation and cancer prevention targets.
      METHODS: Four 7-week withdrawal-oriented treatment groups combined nicotine
      replacement therapy with peer support. Self-report and carbon monoxide register
      data were collected at baseline and 7 weeks. N = 98 gay men were recruited
      through community newspapers and organisations in London UK. RESULTS: At 7 weeks,
      n = 44 (76%) were confirmed as quit using standard UK Government National Health
      Service monitoring forms. In multivariate analysis the single significant
      baseline variable associated with cessation was previous number of attempts at
      quitting (OR 1.48, p = 0.04). CONCLUSIONS: This tailored community-level
      intervention successfully recruited a high-prevalence group, and the outcome data
      compares very favourably to national monitoring data (which reports an average of
      53% success). Implications for national targeted services are considered.

PMID- 15458568
TI  - Fear of nuclear war increases the risk of common mental disorders among young
      adults: a five-year follow-up study.
AB  - BACKGROUND: Evidence on the relation between fear of war and mental health is
      insufficient. We carried out a prospective cohort study to find out whether fear
      of nuclear war is related to increased risk of common mental disorders. METHODS:
      Within two months preceding the outbreak of Persian Gulf War in January 1991,
      1518 adolescents [mean age 16.8 years, SD 0.9] filled in a self-administered
      questionnaire. Of the 1493 respondents, 47% gave their written informed consent
      to participate in the follow-up study. There were no material differences between
      those who chose to respond anonymously and those who volunteered to give their
      name and address for the follow-up study. In 1995, the response to the follow-up
      questionnaire was 92%. Common mental disorders were assessed by 36-item version
      of the General Health Questionnaire [GHQ]. A score 5 or higher was considered to
      indicate caseness. We excluded 23 cases which had used mental health services in
      the year 1991 or earlier and two cases with deficient responses to GHQ. This left
      626 subjects for analysis [400 women]. RESULTS: After adjusting for significant
      mental health risk factors in logistic regression analysis, the risk for common
      mental disorders was found to be significantly related to the increasing
      frequency of fear for nuclear war, high scores of trait anxiety and high scores
      of immature defense style. Elevated risk was confined to the group reporting fear
      of nuclear war once a week or more often [odds ratio 2.05; 95% confidence
      interval 1.29-3.27]. CONCLUSION: Frequent fear of nuclear war in adolescents
      seems to be an indicator for an increased risk for common mental disorders and
      deserves serious attention.

PMID- 15458569
TI  - Efficacy of two once-daily methylphenidate formulations compared across dose
      levels at different times of the day: preliminary indications from a secondary
      analysis of the COMACS study data.
AB  - BACKGROUND: Methylphenidate (MPH) is commonly prescribed in the treatment of
      Attention-Deficit/Hyperactivity Disorder or ADHD. Concerta and Metadate CD are
      once-daily formulations of MPH using different delivery mechanisms resulting in
      different pharmacokinetic profiles. A recent study (COMACS) showed that for near
      milligram (mg) equivalent daily doses, Metadate CD provides greater symptom
      control in the morning (1.5 through 4.5 hours post-dose), while Concerta provides
      greater control in the early evening (12 hours post-dose). Non-inferential
      comparison of effects for different dose levels of the two formulations suggested
      that equivalent levels of morning symptom control could be obtained with lower
      daily doses of Metadate CD than Concerta; the situation being reversed in the
      evening. The current paper presents a secondary analysis that provides a
      statistical test of these observations. METHOD: The COMACS study was a multi
      center, double-blind crossover study of Metadate CD, Concerta and placebo with
      each treatment administered for 1 week. Children were assigned on the basis of
      their pre-trial dosage to either high (Metadate CD 60 mg; Concerta 54 mg), medium
      (Metadate CD 40 mg; Concerta 36 mg) or low doses (Metadate CD 20 mg; Concerta 18
      mg) of MPH, and attended a laboratory school on the 7th day for assessment at 7
      sessions across the day. For the post-hoc comparisons across dose levels
      presented here, total SKAMP scores with the active treatments (adjusted for
      placebo response) were analyzed using an analysis of covariance, with a combined
      measure modeling placebo response across all time period as the covariate.
      RESULTS: Symptom control from 1.5 through 6.0 hours post-dose was as good with
      lower doses of Metadate CD (20 and 40 mg) as with higher doses of Concerta (36
      and 54 mg, respectively). Lower daily doses of Concerta (18 and 36 mg) and higher
      doses of Metadate CD (40 and 60 mg, respectively) gave equivalent control at 7.5
      and 12 hours with Metadate CD giving better control from1.5 through 6.0 hours
      post-dose. CONCLUSIONS: Different delivery profiles of Metadate CD and Concerta
      can be exploited to limit total daily exposure to MPH while at the same targeting
      a specific, especially clinically significant, period of the day. These results
      need to be confirmed in a study in which children are randomly allocated to
      different dose levels of the two formulations and plasma MPH concentrations are
      assessed simultaneously.

PMID- 15458570
TI  - Effect of straining on diaphragmatic crura with identification of the straining
      crural reflex. The "reflex theory" in gastroesophageal competence.
AB  - BACKGROUND: The role of the crural diaphragm during increased intra-abdominal
      pressure is not exactly known. We investigated the hypothesis that the crural
      diaphragm undergoes reflex phasic contraction on elevation of the intra-abdominal
      pressure with a resulting increase of the lower esophageal pressure and
      prevention of gastro-esophageal reflux. METHODS: The esophageal pressure and
      crural diaphragm electromyographic responses to straining were recorded in 16
      subjects (10 men, 6 women, age 36.6 +/- 11.2 SD years) during abdominal hernia
      repair. The electromyogram of crural diaphragm was recorded by needle electrode
      inserted into the crural diaphragm, and the lower esophageal pressure by a saline
      perfused catheter. The study was repeated after crural anesthetization and after
      crural infiltration with saline. RESULTS: The crural diaphragm exhibited resting
      electromyographic activity which showed a significant increase on sudden
      (coughing, p < 0.001) or slow sustained (p < 0.01) straining with a mean latency
      of 29.6 +/- 4.7 and 31.4 +/- 4.5 ms, respectively. Straining led to elevation of
      the lower esophageal pressure which was coupled with the increased
      electromyographic activity of the crural diaphragm. The crural response to
      straining did not occur during crural diaphragm anesthetization, while was not
      affected by saline infiltration. The lower esophageal pressure declined on crural
      diaphragm anesthetization. CONCLUSIONS: Straining effected an increase of the
      electromyographic activity of the crural diaphragm and of the lower esophageal
      pressure. This effect is suggested to be reflex in nature and to be mediated
      through the "straining-crural reflex". The crural diaphragm seems to play a role
      in the lower esophageal competence mechanism. Further studies are required to
      assess the clinical significance of the current results in gastro-esophageal
      reflux disease and hiatus hernia.

PMID- 15458571
TI  - Participant characteristics associated with withdrawal from a large randomized
      trial of spermicide effectiveness.
AB  - BACKGROUND: In most recent large efficacy trials of barrier contraceptive
      methods, a high proportion of participants withdrew before the intended end of
      follow-up. The objective of this analysis was to explore characteristics of
      participants who failed to complete seven months of planned participation in a
      trial of spermicide efficacy. METHODS: Trial participants were expected to use
      the assigned spermicide for contraception for 7 months or until pregnancy
      occurred. In bivariable and multivariable analyses, we assessed the associations
      between failure to complete the trial and 17 pre-specified baseline
      characteristics. In addition, among women who participated for at least 6 weeks,
      we evaluated the relationships between failure to complete, various features of
      their first 6 weeks of experience with the spermicide, and characteristics of the
      study centers and population. RESULTS: Of the 1514 participants in this analysis,
      635 (42%) failed to complete the study for reasons other than pregnancy. Women
      were significantly less likely to complete if they were younger or unmarried, had
      intercourse at least 8 times per month, or were enrolled at a university center
      or at a center that enrolled fewer than 4 participants per month. Noncompliance
      with study procedures in the first 6 weeks was also associated with subsequent
      early withdrawal, but dissatisfaction with the spermicide was not. However, many
      participants without these risk factors withdrew early. CONCLUSIONS: Failure to
      complete is a major problem in barrier method trials that seriously compromises
      the interpretation of results. Targeting retention efforts at women at high risk
      for early withdrawal is not likely to address the problem sufficiently.

PMID- 15458572
TI  - Peroxynitrite decomposition catalyst ameliorates renal damage and protein
      nitration in cisplatin-induced nephrotoxicity in rats.
AB  - BACKGROUND: Oxidative stress is involved in cisplatin-nephrotoxicity. However, it
      has not completely established if reactive nitrogen species and nitrosative
      stress are involved in this experimental model. The purpose of this work was to
      study the role of peroxynitrite, a reactive nitrogen specie, in cisplatin
      nephrotoxicity using the compound 5,10,15,20-tetrakis (4-sulfonatophenyl)
      porphyrinato iron (III) (FeTPPS), a soluble complex able to metabolize
      peroxynitrite. RESULTS: In rats treated with cisplatin (a single intraperitoneal
      dose of 7.5 mg/kg body weight), renal nitrosative stress was made evident by the
      increase in 3-nitrotyrosine on day 3. In addition, cisplatin-induced
      nephrotoxicity was evident by the histological damage of proximal tubular cells
      and by the increase in (a) serum creatinine, (b) blood urea nitrogen, and (c)
      urinary excretion of N-acetyl-beta-D-glucosaminidase and total protein. Cisplatin
      induced nitrosative stress and nephrotoxicity were attenuated by FeTPPS-treatment
      (15 mg/kg body weight, intraperitoneally, every 12 hours for 3 days).
      CONCLUSIONS: Nitrosative stress is involved in cisplatin-induced nephrotoxicity
      in rats. Our data suggest that peroxynitrite is involved, at least in part, in
      cisplatin-induced nephrotoxicity and protein nitration.

PMID- 15458573
TI  - Enhancement of blood-tumor barrier permeability by Sar-[D-Phe8]des-Arg9BK, a
      metabolically resistant bradykinin B1 agonist, in a rat C6 glioma model.
AB  - BACKGROUND: While it is well known that bradykinin B2 agonists increase plasma
      protein extravasation (PPE) in brain tumors, the bradykinin B1 agonists tested
      thus far are unable to produce this effect. Here we examine the effect of the
      selective B1 agonist bradykinin (BK) Sar-[D-Phe8]des-Arg9BK (SAR), a compound
      resistant to enzymatic degradation with prolonged activity on PPE in the blood
      circulation in the C6 rat glioma model. RESULTS: SAR administration significantly
      enhanced PPE in C6 rat brain glioma compared to saline or BK (p < 0.01). Pre
      administration of the bradykinin B1 antagonist [Leu8]-des-Arg (100 nmol/Kg)
      blocked the SAR-induced PPE in the tumor area. CONCLUSIONS: Our data suggest that
      the B1 receptor modulates PPE in the blood tumor barrier of C6 glioma. A possible
      role for the use of SAR in the chemotherapy of gliomas deserves further study.

PMID- 15458574
TI  - Generation of competent bone marrow-derived antigen presenting cells from the
      deer mouse (Peromyscus maniculatus).
AB  - BACKGROUND: Human infections with Sin Nombre virus (SNV) and related New World
      hantaviruses often lead to hantavirus cardiopulmonary syndrome (HCPS), a
      sometimes fatal illness. Lungs of patients who die from HCPS exhibit cytokine
      producing mononuclear infiltrates and pronounced pulmonary inflammation. Deer
      mice (Peromyscus maniculatus) are the principal natural hosts of SNV, in which
      the virus establishes life-long persistence without conspicuous pathology. Little
      is known about the mechanisms SNV employs to evade the immune response of deer
      mice, and experimental examination of this question has been difficult because of
      a lack of methodologies for examining such responses during infection. One such
      deficiency is our inability to characterize T cell responses because susceptible
      syngeneic deer mice are not available. RESULTS: To solve this problem, we have
      developed an in vitro method of expanding and generating competent antigen
      presenting cells (APC) from deer mouse bone marrow using commercially-available
      house mouse (Mus musculus) granulocyte-macrophage colony stimulating factor.
      These cells are capable of processing and presenting soluble protein to antigen
      specific autologous helper T cells in vitro. Inclusion of antigen-specific deer
      mouse antibody augments T cell stimulation, presumably through Fc receptor
      mediated endocytosis. CONCLUSIONS: The use of these APC has allowed us to
      dramatically expand deer mouse helper T cells in culture and should permit
      extensive characterization of T cell epitopes. Considering the evolutionary
      divergence between deer mice and house mice, it is probable that this method will
      be useful to other investigators using unconventional models of rodent-borne
      diseases.

PMID- 15458575
TI  - Genome wide analysis of common and specific stress responses in adult drosophila
      melanogaster.
AB  - BACKGROUND: During their life, multicellular organisms are challenged with
      oxidative stress. It is generated by several reactive oxygen species (ROS), may
      limit lifespan and has been related to several human diseases. ROS can generate a
      wide variety of defects in many cellular components and thus the response of the
      organism challenged with oxidative stress may share some features with other
      stress responses. Conversely, in spite of recent progress, a complete functional
      analysis of the transcriptional responses to different oxidative stresses in
      model organisms is still missing. In addition, the functional significance of
      observed transcriptional changes is still elusive. RESULTS: We used
      oligonucleotide microarrays to address the specificities of transcriptional
      responses of adult Drosophila to different stresses induced by paraquat and H2O2,
      two oxidative stressors, and by tunicamycin which induces an endoplasmic
      reticulum (ER) stress. Both specific and common responses to the three stressors
      were observed and whole genome functional analysis identified several important
      classes of stress responsive genes. Within some functional classes, we observed
      that isozymes do not all behave similarly, which may reflect unsuspected
      functional specificities. Moreover, genetic experiments performed on a subset of
      lines bearing mutations in genes identified in microarray experiments showed that
      a significant number of these mutations may affect resistance of adult Drosophila
      to oxidative stress. CONCLUSIONS: A long term common stress response to paraquat-
      or H2O2-induced oxidative stresses and ER stress is observed for a significant
      number of genes. Besides this common response, the unexpected complexity of the
      stress responses to oxidative and ER stresses in Drosophila, suggest significant
      specificities in protective properties between genes associated to the same
      functional classes. According to our functional analysis, a large part of the
      genome may play a role in protective mechanisms against oxidative stress in
      Drosophila.

PMID- 15458576
TI  - On modeling locus heterogeneity using mixture distributions.
AB  - BACKGROUND: Locus heterogeneity poses a major difficulty in mapping genes that
      influence complex genetic traits. A widely used approach to deal with this
      problem involves modeling linkage data in terms of finite mixture distributions.
      In its simplest setup, also known as the admixture approach, a single parameter
      is used to model the probability that the disease-causing gene of a family is
      linked to a reference marker. This parameter is usually interpreted as the
      overall proportion of linked families. RESULTS: In this article, we address two
      issues regarding the admixture approach. First, we tackle the question of whether
      the single parameter of linked proportion is well defined in general. By
      formulating the likelihood under a classification scheme based on distributions,
      we show that such a parameter is meaningful only when a certain well
      characterized condition is met. Second, we study a condition given in the
      literature for validating the admixture approach. A counter example is
      constructed to illustrate that the condition does not necessarily lead to valid
      estimates. CONCLUSIONS: Estimators from the admixture approach may be
      inconsistent. This holds even if a condition given in the literature to validate
      the approach is satisfied.

PMID- 15458578
TI  - Control and maintenance of mammalian cell size: response.
AB  - A response to Cooper S: Control and maintenance of mammalian cell size. BMC Cell
      Biol 2004, 5:35.

PMID- 15458577
TI  - Intracellular shuttling of a Drosophila APC tumour suppressor homolog.
AB  - BACKGROUND: The Adenomatous polyposis coli (APC) tumour suppressor is found in
      multiple discrete subcellular locations, which may reflect sites of distinct
      functions. In Drosophila epithelial cells, the predominant APC relative (E-APC)
      is concentrated at the apicolateral adherens junctions. Genetic analysis
      indicates that this junctional association is critical for the function of E-APC
      in Wnt signalling and in cellular adhesion. Here, we ask whether the junctional
      association of E-APC is stable, or whether E-APC shuttles between the plasma
      membrane and the cytoplasm. RESULTS: We generated a Drosophila strain that
      expresses E-APC (dAPC2) tagged with green fluorescent protein (GFP-E-APC) and we
      analysed its junctional association with fluorescence recovery after
      photobleaching (FRAP) experiments in live embryos. This revealed that the
      junctional association of GFP-E-APC in epithelial cells is highly dynamic, and is
      far less stable than that of the structural components of the adherens junctions,
      E-cadherin, alpha-catenin and Armadillo. The shuttling of GFP-E-APC to and from
      the plasma membrane is unaltered in mutants of Drosophila glycogen synthase
      kinase 3 (GSK3), which mimic constitutive Wingless signalling. However, the
      stability of E-APC is greatly reduced in these mutants, explaining their apparent
      delocalisation from the plasma membrane as previously observed. Finally, we show
      that GFP-E-APC forms dynamic patches at the apical plasma membrane of late
      embryonic epidermal cells that form denticles, and that it shuttles up and down
      the axons of the optic lobe. CONCLUSIONS: We conclude that E-APC is a highly
      mobile protein that shuttles constitutively between distinct subcellular
      locations.

PMID- 15458579
TI  - GeneXplorer: an interactive web application for microarray data visualization and
      analysis.
AB  - BACKGROUND: When publishing large-scale microarray datasets, it is of great value
      to create supplemental websites where either the full data, or selected subsets
      corresponding to figures within the paper, can be browsed. We set out to create a
      CGI application containing many of the features of some of the existing
      standalone software for the visualization of clustered microarray data. RESULTS:
      We present GeneXplorer, a web application for interactive microarray data
      visualization and analysis in a web environment. GeneXplorer allows users to
      browse a microarray dataset in an intuitive fashion. It provides simple access to
      microarray data over the Internet and uses only HTML and JavaScript to display
      graphic and annotation information. It provides radar and zoom views of the data,
      allows display of the nearest neighbors to a gene expression vector based on
      their Pearson correlations and provides the ability to search gene annotation
      fields. CONCLUSIONS: The software is released under the permissive MIT Open
      Source license, and the complete documentation and the entire source code are
      freely available for download from CPAN http://search.cpan.org/dist/Microarray
      GeneXplorer/.

PMID- 15458581
TI  - The "schola medica salernitana": the forerunner of the modern university medical
      schools.
AB  - The schola medica salernitana is considered the oldest medical school of modern
      civilization. Salerno's long medical tradition began during the Greco-Roman
      period in a Greek colony named Elea, where Parmenides decided to found a medical
      school. The fame of the school became more and more important during the 10th
      century, and it was best known in the 11th century. In the middle of 12th
      century, the school was at its apogee, and Salerno provided a notable
      contribution to the formulation of a medical curriculum for medieval
      universities. The most famous work of the Salernitan School was the Regimen
      Sanitatis Saleritanum, a Latin poem of rational, dietetic, and hygienic precepts,
      many of them still valid today. The school also produced a physician's reference
      book, with advice on how to treat a patient, a sort of code of conduct to help
      the physician to respect the patient and his or her relatives. The first science
      based surgery appeared on the scene of the discredited medieval practice in
      Salerno, thanks to Roger of Salerno and his fellows. He wrote a book on surgery,
      called Rogerina or Post Mundi Fabricam, in which surgery from head to toe is
      described, with surprising originality. The important contribution to the School
      of Salerno made by women as female practitioners is outlined, and among them,
      Trotula de Ruggiero was the most renowned. The period when the School of Salerno,
      universally recognized as the forerunner of the modern universities, became a
      government academy was when Frederick II reigned over the Kingdom of the Two
      Sicilies, as Emperor of the Holy Roman Empire.

PMID- 15458580
TI  - A comprehensive comparison of comparative RNA structure prediction approaches.
AB  - BACKGROUND: An increasing number of researchers have released novel RNA structure
      analysis and prediction algorithms for comparative approaches to structure
      prediction. Yet, independent benchmarking of these algorithms is rarely performed
      as is now common practice for protein-folding, gene-finding and multiple-sequence
      alignment algorithms. RESULTS: Here we evaluate a number of RNA folding
      algorithms using reliable RNA data-sets and compare their relative performance.
      CONCLUSIONS: We conclude that comparative data can enhance structure prediction
      but structure-prediction-algorithms vary widely in terms of both sensitivity and
      selectivity across different lengths and homologies. Furthermore, we outline some
      directions for future research.

PMID- 15458582
TI  - Padua: the renaissance of human anatomy and medicine.
AB  - The city and University of Padua have a long tradition and a great reputation in
      anatomic studies, dating from the founding of the university in the year 1222. We
      present a historical review of the study of human anatomy, for which Padua was a
      most important center. The background for the development of this culture was
      represented by the scientific freedom and political wisdom of the Serenissima
      Republic of Venice, a liberal and tolerant state in the midst of a feudal,
      imperial, and pontifical Europe. During the second half of the 15th century, the
      flourishing trade and cultural, social, and political life of Venice attracted a
      great number of scientists and students from all over Europe who contributed to
      the establishment of Padua as an international center for culture and the
      sciences. Vesalio, Fabrizio d'Acquapendente, and Giovanni Battista Morgagni
      represent milestones in the history of anatomy as well as in medicine and
      surgery. History shows that anatomy and surgery evolved together, just as anatomy
      of the nervous system and neurosurgery developed in tandem. The tradition of
      neurosurgery in Padua is considered one the most important schools in Italy.

PMID- 15458583
TI  - Lo Spedale di Poveri, the hospital for the poor in Milan: 15th to 20th century.
AB  - The construction of the Hospital for the Poor was begun in Milan in 1451 at the
      instigation of Francesco Sforza, Duke of Milan. In contrast to what had happened
      during the Dark Ages of the Medieval period, the new hospital was extraordinary
      both in construction and in medical organization. Wards for the patients were
      separated according to diseases, infective and noninfective, and according to
      sex. Each patient had his or her own bed and was fed adequately and kept warm.
      Patients were no longer treated by astrologers or monks but rather by doctors who
      had studied medicine at the University of Pavia. Each ward had its own doctor and
      surgeon, and from 1558 on, there was a doctor on duty in the hospital 24 hours a
      day. The hospital had its own pharmacy and drug reference book. The Hospital for
      the Poor, or Ca Granda (Big House), or the Ospedale Maggiore, as it was variously
      called from the 15th to the 19th centuries, became a training ground for anatomic
      and clinical studies. It was only in 1929 that a Faculty of Medicine was set up
      at Ospedale Maggiore.

PMID- 15458584
TI  - An intriguing fragment of pre-hippocratic medicine in Aeschylus.
AB  - Information scattered in several passages of Greek tragedies of the 5th century
      BC contributes to our knowledge of pre-Hippocratic medicine and throws light on
      the cultural background of the Hippocratic writers. In this regard, the work of
      Aeschylus is noteworthy, because it contains fragments of an ideal-conjectural
      conception preceding the empirical approach based on observation and experience.
      The idealized meaning attributed to the term muupsilonepsilonlambdaoc (marrow),
      compared with both Homeric epics and Hippocratic writings, represents a reliable
      index of the evolution of the ancient medical thought.

PMID- 15458585
TI  - Treatment of unruptured cerebral aneurysms by embolization with guglielmi
      detachable coils: case-fatality, morbidity, and effectiveness in preventing
      bleeding--a systematic review of the literature.
AB  - OBJECTIVE: Guglielmi detachable coils (GDCs) increasingly are being used to treat
      unruptured cerebral aneurysms (UCAs). We systematically reviewed the literature
      to assess the case-fatality and permanent morbidity rates of GDC embolization of
      UCAs and the postembolization bleeding rate. METHODS: Through a MEDLINE search of
      the English, Italian, and French literature from January 1990 through December
      2002, we retrieved studies on GDC embolization of aneurysms and extracted data on
      UCAs. Inclusion criteria were: 1) attempted GDC embolization of at least five
      consecutive patients with UCAs, 2) reported percentage of at least either case
      fatality or permanent morbidity rate or crude data allowing an independent
      calculation. When data on UCAs could not be characterized with certainty among
      data on other, different lesions, the study was rejected. RESULTS: We included 30
      studies. One thousand three hundred seventy-nine patients were available for the
      calculation of the case-fatality rate, 794 for the permanent morbidity rate, and
      703 for the bleeding rate. The case-fatality rate was 0.6% (95% confidence
      interval, 0.2-1%), the permanent morbidity rate was 7% (95% confidence interval,
      5.3-8.7%), and the bleeding rate was 0.9% per year (95% confidence interval, 0.41
      1.4%). Only incompletely coiled UCAs of 10 mm or more accounted for the bleeding
      events. Morbidity decreased from 8.6% to 4.5% (P < 0.05) when the midyear of
      study (average calendar year of treatment) was 1995 or later. CONCLUSION: GDC
      embolization of UCAs is relatively safe, and the outcome is progressively
      improving. Partial embolization of UCAs of 10 mm or more is unlikely to provide
      an acceptable protection. Most of the source publications suffer from
      methodological weaknesses. Prospective studies with longer follow-up periods are
      needed to definitively assess the effectiveness of GDCs on UCAs.

PMID- 15458586
TI  - Effect of clipping, craniotomy, or intravascular coiling on cerebral vasospasm
      and patient outcome after aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Although several recent studies have suggested that the incidence of
      vasospasm after aneurysmal subarachnoid hemorrhage is lower in patients
      undergoing aneurysmal coiling as compared with clipping, other studies have had
      conflicting results. We reviewed our experience over 8 years and assessed whether
      clipping, craniotomy, or coiling affects patient outcomes or the risk for
      vasospasm. METHODS: We included 515 patients with aneurysmal subarachnoid
      hemorrhage, identified prospectively from November 2000 to February 2003 (243
      patients) and retrospectively from November 1995 to October 2000 (272 patients),
      by using International Classification of Diseases, 9th Revision, codes for
      subarachnoid hemorrhage. We classified patients as follows: clipping (413
      patients), coiling (79 patients), and craniotomy (436 patients, including all 413
      patients who underwent clipping plus 23 who underwent coiling as well as
      craniotomy for various reasons). We studied four outcome measures: total
      vasospasm, symptomatic vasospasm, poor outcome (modified Rankin score 3-6), and
      in-hospital mortality. To assess the risk of total vasospasm and symptomatic
      vasospasm, we performed multivariate regression analyses adjusting for age,
      Fisher grade, Hunt and Hess grade, aneurysm location (anterior versus posterior
      circulation), and aneurysm treatment modality. To assess the risk for poor
      outcome and in-hospital mortality, we adjusted for all the above variables as
      well as for total and symptomatic vasospasm. RESULTS: In the clipping group there
      was 63% total vasospasm and 28% symptomatic vasospasm; in the coiling group there
      was 54% total vasospasm and 33% symptomatic vasospasm; and in the craniotomy
      group there was 64% total vasospasm and 28% symptomatic vasospasm. In the
      multivariate analysis, age <50 years (P = 0.0099) and Fisher Grade 3 (P <
      0.00001) predicted total vasospasm, and Fisher Grade 3 (P < 0.000001) and Hunt
      and Hess Grade IV or V (P = 0.018) predicted symptomatic vasospasm. Predictors of
      poor outcome were age >or=50 years (P < 0.0001), Fisher Grade 3 (P = 0.0072),
      Hunt and Hess Grade IV or V (P < 0.00001), symptomatic vasospasm (P < 0.0001),
      and coiling (P = 0.0314 versus clipping and P = 0.045 versus craniotomy).
      Predictors of in-hospital mortality were age >or= 50 years (P = 0.0030), Hunt and
      Hess Grade IV or V (P = 0.0001), symptomatic vasospasm (P < 0.00001), and coiling
      (P = 0.008 versus clipping and P = 0.0013 versus craniotomy). There was no
      significant difference in total vasospasm or symptomatic vasospasm when patients
      who underwent clipping or craniotomy were compared with patients who underwent
      coiling. In patients with Hunt and Hess Grade I to III ("good grade"), clipping
      and craniotomy were associated with better outcome and less in-hospital
      mortality, but there was no difference in total vasospasm or symptomatic
      vasospasm versus coiling. In patients with Hunt and Hess Grade IV or V ("poor
      grade"), there was no difference in any outcome measure among the treatment
      groups. CONCLUSION: In a single-center, retrospective, nonrandomized study,
      performance of clipping and/or craniotomy had significantly better outcome and
      lower mortality at discharge than coiling in good-grade patients but had no
      effect on total vasospasm or symptomatic vasospasm in good- or poor-grade
      patients.

PMID- 15458587
TI  - Relationship of local infarctions to cognitive and psychosocial impairments after
      aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Previous studies suggest that cognitive and psychosocial impairments
      after subarachnoid hemorrhage (SAH) result from diffuse brain damage caused by
      the initial bleeding rather than from focal lesions. We describe the relationship
      of local infarctions to these impairments and explore how well test and
      questionnaire results explain psychosocial outcome. METHODS: A total of 170
      patients, selected from a consecutive series of patients with aneurysmal SAH,
      underwent neurological and neuroradiological examinations, and 138 of them were
      assessed with neuropsychological tests and questionnaires 1 year after SAH.
      RESULTS: Patients with left and bilateral infarctions performed worse on verbal
      memory tests than the other patients, and patients with left infarctions had more
      impaired working capacity than those with no infarction. The indices of the
      severity of SAH were related to reductions in both working capacity and social
      activity but less clearly to poor test performances. Whereas the modified Rankin
      scale was the most important correlate of working capacity, performance on
      cognitive tests was associated with return to work, and questionnaire ratings of
      mental impairments correlated with reduced working capacity and decreased social
      activity. CONCLUSION: Left-hemisphere infarctions cause deficits in verbal memory
      and working capacity. The severity of SAH is associated with impairments in
      working capacity and social activity rather than with specific cognitive
      deficits. Patients' and partners' opinions on patients' mental impairments could
      provide complementary information to clinical grades and cognitive tests in the
      evaluation of outcome after SAH.

PMID- 15458588
TI  - Functional magnetic resonance imaging and optical imaging for dominant-hemisphere
      perisylvian arteriovenous malformations.
AB  - OBJECTIVE: In this study, we developed an a priori system to stratify surgical
      intervention of perisylvian arteriovenous malformations (AVMs) in 20 patients. We
      stratified the patients into three categories based on preoperative functional
      magnetic resonance imaging (fMRI) language activation pattern and relative
      location of the AVM. METHODS: In Group I (minimal risk), the AVM was at least one
      gyrus removed from language activation, and patients subsequently underwent
      asleep resection. In Group II (high risk), the AVM and language activation were
      intimately associated. Because the risk of postoperative language deficit was
      high, these patients were then referred to radiosurgery. In Group III
      (indeterminate risk), the AVM and language were adjacent to each other. The risk
      of language deficit could not be predicted on the basis of the fMRI alone. These
      patients underwent awake craniotomy with electrocortical stimulation mapping and
      optical imaging of intrinsic signals for language mapping. RESULTS: All patients
      from Group I (minimal risk) underwent asleep resection without deficit. All Group
      II (high-risk) patients tolerated radiosurgery without complication. In Group III
      (indeterminate risk), three patients underwent successful resection, whereas two
      underwent aborted resection after intracranial mapping. CONCLUSION: We advocate
      the use of fMRI to assist in the preoperative determination of operability by
      asleep versus awake craniotomy versus radiosurgery referral. In addition, we
      advocate the use of all three functional mapping (fMRI, electrocortical
      stimulation mapping, and optical imaging of intrinsic signals) techniques to
      clarify the eloquence score of the Spetzler-Martin system before definitive
      treatment (anesthetized resection versus radiosurgery versus intraoperative
      resection versus intraoperative closure and radiosurgery referral).

PMID- 15458589
TI  - Spinal dural arteriovenous fistulae: analysis of outcome in relation to
      pretreatment indicators.
AB  - OBJECTIVE: The outcome of treatment for a spinal dural arteriovenous fistula is
      unpredictable. In this study, we reviewed the outcome of patients treated for
      this condition, in relation to pretreatment indicators. METHODS: We reviewed the
      records of 37 consecutive patients treated either surgically or endovascularly in
      our department between 1989 and 2002. RESULTS: At follow-up, 78% of the patients
      reported improvement. Those with motor symptoms had the best outcome: improvement
      was achieved in more than 60% of the patients, amounting to 1 or 2 points on the
      Aminoff scale. Sensory disorders improved in 43% of cases, pain in 61%, and
      sphincter impairment in only 37%. Patients with a fistula in the lower thoracic
      region did better than those with fistulae in other locations. CONCLUSION: The
      clinical state before treatment is certainly relevant in predicting outcome. Age
      and duration of the symptoms before treatment have no direct relation to the
      chances of improvement with treatment, particularly when motor improvement is
      considered. The modality of onset of symptoms and location of the fistula play
      significant roles, also: a fistula in the lower thoracic segment was associated
      with more severe symptoms but tended to improve more (83%, P = 0.04) after
      treatment. Midthoracic and lumbar fistulae showed a lower incidence of
      improvement (<50%).

PMID- 15458590
TI  - Taurine detection by proton magnetic resonance spectroscopy in medulloblastoma:
      contribution to noninvasive differential diagnosis with cerebellar astrocytoma.
AB  - OBJECTIVE: We sought to evaluate whether taurine detection in short-echo (20 ms)
      proton magnetic resonance spectroscopy contributes to the noninvasive
      differential diagnosis between medulloblastoma and cerebellar astrocytoma in
      children and young adults. These two types of tumor have very different prognoses
      and may be difficult to differentiate by neuroradiological or clinical means.
      METHODS: Single-voxel proton magnetic resonance spectra of tumors were acquired
      at 1.5 T in 14 patients with biopsy-proven primary cerebellar tumors (six
      medulloblastomas, seven astrocytomas, and one mixed astroependymoma) using short
      echo time (20 ms) and long-echo time (135 ms). For taurine assignment,
      qualitative analysis was performed on short-echo time spectra and results were
      compared in vitro with spectra of model solutions. Perchloric acid extracts of
      postsurgical tumor biopsies were performed in two medulloblastoma cases. RESULTS:
      Taurine detection was demonstrated in all patients with medulloblastoma and in
      none of those with astrocytoma. We were unable to ascertain any relationship
      between taurine and metastatic spread within the medulloblastoma group.
      CONCLUSION: Medulloblastomas characteristically seem to show taurine detectable
      in vivo by short-echo proton magnetic resonance spectroscopy, which may help to
      discriminate medulloblastoma from cerebellar astrocytoma.

PMID- 15458591
TI  - Operative findings and outcomes of microvascular decompression for trigeminal
      neuralgia in 35 patients affected by multiple sclerosis.
AB  - OBJECTIVE: The concept of vascular compression of the trigeminal root as the main
      etiological factor in idiopathic trigeminal neuralgia has achieved widespread
      acceptance, and microvascular decompression (MVD) is a well-established surgical
      procedure for its treatment. Multiple sclerosis (MS) has long been considered to
      be an absolute contraindication to MVD because of the supposed exclusive
      causative role of a demyelinating lesion affecting the trigeminal root entry
      zone. Magnetic resonance imaging preoperative identification of suspicious
      vessels along the cisternal course of the trigeminal nerve in MS patients raises
      the question of a possible causative role of vascular compression in MS patients.
      METHODS: We describe magnetic resonance imaging findings, surgical findings, and
      outcomes in 35 MS patients who underwent MVD for medically intractable trigeminal
      neuralgia. Results were assessed by clinical follow-up and periodic phone
      surveys. The mean follow-up was 44 months (range, 6-108 mo). RESULTS: Magnetic
      resonance imaging revealed the presence of demyelinating lesions affecting the
      brainstem trigeminal pathways of the painful side in 26 (74%) of 35 patients.
      During surgery, severe neurovascular compression at the trigeminal root entry
      zone was found in 16 (46%) of 35 patients. The long-term outcome was excellent in
      39%, good in 14%, fair in 8%, and poor in 39% of patients. No statistically
      significant prognostic factor predicting good outcome could be found. There was
      no mortality, with a 2.5% long-term morbidity rate (facial nerve palsy in one
      patient). CONCLUSION: Results of MVD in trigeminal neuralgia MS patients are much
      less satisfactory than in the idiopathic group, indicating that central
      mechanisms play a major role in pain genesis.

PMID- 15458592
TI  - Microvascular decompression for trigeminal neuralgia in the elderly: a review of
      the safety and efficacy.
AB  - OBJECTIVE: To critically examine the efficacy and safety of microvascular
      decompression (MVD) for trigeminal neuralgia (TN) in elderly patients. METHODS:
      We performed a retrospective review of medical records, followed by prospective
      follow-up. The outcome data from 44 MVD operations for TN performed in 40
      consecutive patients with a mean age of 65 years (range, 60-75 yr) in the period
      1991 to 2001 were compared with those from 40 younger control subjects (mean age,
      46 yr; range, 20-59 yr) operated on during the same period. RESULTS: The median
      time from diagnosis of TN to MVD in the older patients was 7 years (range, 1-22
      yr), compared with 3 years (range, 3 mo to 20 yr) in the younger group (P =
      0.02). With the exception of one, all patients in this study were classified as
      American Society of Anesthesiologist Grade 1 or 2. Initial pain relief was
      achieved in 98 and 100% of the patients in the study and control groups,
      respectively. There were no operative mortalities or life-threatening
      morbidities. Transient facial numbness and diplopia occurred in both groups.
      Headaches, nausea, and vomiting were more frequent in the younger patients,
      whereas wound infection and confusion were more common in the older patients. The
      mean length of hospital stay was 5.4 days (range, 3-10 d) for the older patients,
      compared with 5.3 days (range, 3-9 d) for the control group (P = 0.4). After
      average follow-ups of 30 and 33 months, the pain recurred in 24 and 27% of the
      patients in the elderly and control groups, respectively. CONCLUSION: MVD is
      underused in the elderly despite being both safe and effective. Fitness and not
      age should be the key in deciding the treatment options. It is proposed that any
      patient with medically refractory TN who is fit for general anesthesia should be
      given the opportunity to choose MVD.

PMID- 15458593
TI  - Relationship between valve opening pressure, body position, and intracranial
      pressure in normal pressure hydrocephalus: paradigm for selection of programmable
      valve pressure setting.
AB  - OBJECTIVE: There is little scientific basis for guidance in selecting the optimal
      valve for the treatment of normal pressure hydrocephalus. The aim of this study
      was to determine the programmable valve opening pressure setting that would
      result in a slight reduction in intracranial pressure (ICP) after a
      ventriculoperitoneal shunt is implanted. We also assessed whether shunt-induced
      ICP could be predicted on the basis of a simple hydrodynamic equation. METHODS:
      In this prospective study of 11 patients with normal pressure hydrocephalus, ICP
      was measured before and after implantation of a shunt incorporating a
      programmable valve without an antisiphon device. Pressure measurements, including
      intraperitoneal pressure, were recorded at body angles ranging from 0 to 55
      degrees and at valve settings ranging from 30 to 200 mm H(2)O. Measured ICP
      values were compared with values computed using a simple hydrodynamic equation.
      RESULTS: Even at a valve setting greater than the mean baseline ICP (200 mm
      H(2)O), the supine ICP was significantly lower than the baseline value (baseline
      ICP, 164 +/- 64 mm H(2)O; postoperative ICP, 125 +/- 69 mm H(2)O, P = 0.04).
      Valve pressure did not equate 1:1 with the measured postoperative ICP.
      Comprehensive ICP measurements at upright body positions demonstrated a stepwise
      reduction in ICP rather than a precipitous decline as a result of so-called
      siphoning. CONCLUSION: This study indicates that very high valve opening pressure
      settings may be optimal for the initial treatment of normal pressure
      hydrocephalus. The relationship between ICP and opening pressure valves is linear
      but not predicted by simple hydrodynamics.

PMID- 15458594
TI  - Concussion in professional football: repeat injuries--part 4.
AB  - OBJECTIVE: A 6-year study was conducted to determine the signs, symptoms, and
      management of repeat concussion in National Football League players. METHODS:
      From 1996 to 2001, concussions were reported by 30 National Football League teams
      using a standardized reporting form filled out by team physicians with input from
      athletic trainers. Signs and symptoms were grouped by general symptoms, somatic
      complaints, cranial nerve effects, cognition problems, memory problems, and
      unconsciousness. Medical actions taken and management were recorded. RESULTS:
      Data were captured for 887 concussions in practices and games involving 650
      players. A total of 160 players experienced repeat injury, with 51 having three
      or more concussions during the study period. The median time between injuries was
      374.5 days, with only six concussions occurring within 2 weeks of the initial
      injury. Repeat concussions were more prevalent in the secondary (16.9%), the kick
      unit on special teams (16.3%), and wide receivers (12.5%). The ball return
      carrier on special teams (odds ratio [OR] = 2.08, P = not significant) and
      quarterbacks (OR = 1.92, P < 0.1) had elevated odds for repeat injury, followed
      by the tight end (OR = 1.24, P = not significant) and linebackers (OR = 1.22, P =
      not significant). There were similar signs and symptoms with single and repeat
      concussion, except for a higher prevalence of somatic complaints in players on
      their repeat concussions compared with their first concussion (27.5% versus
      18.8%, P < 0.05). More than 90% of players were managed by rest, and 57.5% of
      those with second injuries returned to play within a day. Players with three or
      more concussions had signs, symptoms, and treatment similar to those with only a
      single injury. CONCLUSION: The most vulnerable players for repeat concussion in
      professional football are the ball return carrier on special teams and
      quarterbacks. Single and repeat concussions are managed conservatively with rest,
      and most players return quickly to play.

PMID- 15458595
TI  - Hyperglycemia and brain tissue pH after traumatic brain injury.
AB  - OBJECTIVE: Hyperglycemia occurring after head injury is associated with poor
      neurological outcome. We tested the hypothesis that blood glucose levels are
      associated with brain tissue pH (pH(b)) and that the correction of hyperglycemia
      would result in an improvement in pH(b). METHODS: This is a retrospective
      analysis of a prospectively collected database. Thirty-four patients in a
      tertiary care neuroscience critical care unit with major traumatic brain injury
      underwent pH(b) monitoring. RESULTS: A total of 428 glucose measurements were
      recorded during pH(b) monitoring. Mean glucose level was 7.1 mmol/L (range, 2.8
      21.7 mmol/L) and median (interquartile range) pH(b) was 7.11 mmol/L (7.00-7.19
      mmol/L). To account for the correlated, unbalanced nature of the data, a linear
      generalized estimating equation model was created. This model predicted that for
      each 1 mmol/L increase in blood glucose, pH(b) changed by -0.011 mmol/L (95%
      confidence interval, -0.016 to -0.005 mmol/L; P < 0.001). This relationship
      remained significant in a multivariable model that included cerebral perfusion
      pressure, brain tissue oxygen and carbon dioxide tension, and brain temperature.
      Twenty-one episodes of significant hyperglycemia (>or=11.1 mmol/L) treated with
      intravenous insulin were identified. Insulin therapy significantly reduced blood
      glucose concentration from a median (interquartile range) of 11.9 mmol/L (range,
      11.4-13.6 mmol/L) to 8.8 mmol/L (range, 7.3-9.6 mmol/L; P < 0.001). Baseline
      pH(b) was not significantly different from pH(b) associated with the subsequent
      glucose reading of less than 11.1 mmol/L (P = 0.29), but there was a suggestion
      of improvement if the change in blood glucose was large. CONCLUSION: Blood
      glucose is associated with brain tissue acidosis in patients with major head
      injury. Prospective studies are required to confirm these results and to
      determine whether treatment of hyperglycemia improves outcome.

PMID- 15458596
TI  - Gilliatt-Sumner hand revisited: a 25-year experience.
AB  - OBJECTIVE: Thirty-three patients with true neurogenic thoracic outlet syndrome,
      or Gilliatt-Sumner hand, underwent surgical treatment at Louisiana State
      University during a 25-year period. This study retrospectively evaluated the
      outcome referable to pain and motor function in these patients. METHODS: All
      patients had the typical Gilliatt-Sumner hand, secondary to compression of C8,
      T1, and/or lower trunk. Nineteen patients underwent an anterior supraclavicular
      approach, and 15 patients underwent a posterior subscapular approach to the
      brachial plexus. Nerve action potential recordings showed plexus involvement
      close to the spine, at the level of the junction of the spinal nerves to the
      lower trunk. RESULTS: Pain, present in 22 patients, improved in 21. Mild motor
      deficit improved in 12 of 14 patients. Severe motor deficit improved partially in
      14 of 20 patients. CONCLUSION: The diagnosis of true neurogenic thoracic outlet
      syndrome provides a clear operative indication. Surgical decompression needs to
      involve the medial portion of the plexus, and especially the spinal nerves. An
      anterior supraclavicular approach is preferred in most cases. If there is a large
      cervical rib or there has been a prior anterior operation, then a posterior
      subscapular approach is indicated.

PMID- 15458597
TI  - Recommendations on management of sport-related concussion: summary of the
      National Athletic Trainers' Association position statement.

PMID- 15458598
TI  - Thoracic outlet syndrome.
AB  - OBJECTIVE: Thoracic outlet syndrome (TOS) is one of the most controversial
      clinical entities in medicine. We provide a review of this difficult-to-treat
      disorder, including a brief overview, clinical presentations, surgical anatomy,
      treatment options, and outcomes. METHODS: TOS represents a spectrum of disorders
      encompassing three related syndromes: compression of the brachial plexus
      (neurogenic TOS), compression of the subclavian artery or vein (vascular TOS),
      and the nonspecific or disputed type of TOS. Neurovascular compression may be
      observed most commonly in the interscalene triangle, but it also has been
      described in the costoclavicular space and in the subcoracoid space. Patients
      present with symptoms and signs of arterial insufficiency, venous obstruction,
      painless wasting of intrinsic hand muscles, paresthesia, and pain. A careful and
      detailed medical history and physical examination are the most important
      diagnostic tools for proper identification of TOS. Electromyography, nerve
      conduction studies, and imaging of the cervical spine and the chest also can
      provide helpful information regarding diagnosis. Clinical management usually
      starts with conservative treatment including exercise programs and physical
      therapy; when these therapies fail, patients are considered for surgery. Two of
      the most commonly used surgical approaches are the supraclavicular exposure and
      the transaxillary approach with first rib resection. On occasion, these
      approaches may be combined or, alternatively, posterior subscapular exposure may
      be used in selected patients. CONCLUSION: TOS is perhaps the most difficult
      entrapment neuropathy encountered by neurosurgeons. Surgical intervention is
      indicated for vascular and true neurogenic TOS and for some patients with the
      common or nonspecific type of TOS in whom nonoperative therapies fail. With
      careful patient selection, operative intervention usually yields satisfactory
      results.

PMID- 15458599
TI  - Functional magnetic resonance imaging-integrated neuronavigation: correlation
      between lesion-to-motor cortex distance and outcome.
AB  - OBJECTIVE: The integration of functional magnetic resonance imaging (fMRI) data
      into neuronavigation is a new concept for surgery adjacent to the motor cortex.
      However, the clinical value remains to be defined. In this study, we investigated
      the correlation between the lesion-to-fMRI activation distance and the occurrence
      of a new postoperative deficit. METHODS: fMRI-integrated "functional"
      neuronavigation was used for surgery around the motor strip in 54 patients.
      During standardized paradigms for hand, foot, and tongue movements, echo-planar
      imaging T2* blood oxygen level-dependent sequences were acquired and processed
      with BrainVoyager 2000 software (Brain Innovation, Maastricht, The Netherlands).
      Neuronavigation was performed with the VectorVision(2) system (BrainLAB,
      Heimstetten, Germany). For outcome analysis, patient age, histological findings,
      size of lesion, distance to the fMRI areas, preoperative and postoperative
      Karnofsky index, postoperative motor deficit, and type of resection were
      analyzed. RESULTS: In 45 patients, a gross total resection (>95%) was performed,
      and for 9 lesions (low-grade glioma, 4; glioblastoma, 5), a subtotal resection
      (80-95%) was achieved. The neurological outcome improved in 16 patients (29.6%),
      was unchanged in 29 patients (53.7%), and deteriorated in 9 patients (16.7%).
      Significant predictors of a new neurological deficit were a lesion-to-activation
      distance of less than 5 mm (P < 0.01) and incomplete resection (P < 0.05).
      CONCLUSION: fMRI-integrated neuronavigation is a useful concept to assess the
      risk of a new motor deficit after surgery. Our data suggest that a lesion-to
      activation distance of less than 5 mm is associated with a higher risk of
      neurological deterioration. Within a 10-mm range, cortical stimulation should be
      performed. For a lesion-to-activation distance of more than 10 mm, a complete
      resection can be achieved safely. The visualization of fiber tracks is desirable
      to complete the representation of the motor system.

PMID- 15458600
TI  - Feasibility of radiosurgery for malignant brain tumors in infants by use of image
      guided robotic radiosurgery: preliminary report.
AB  - OBJECTIVE: The benefits of radiation therapy are generally denied to infants with
      malignant brain tumors because of the risk of devastating cognitive decline.
      Efforts to limit this morbidity with radiosurgical techniques have not been
      feasible for infants because of the dual requirements of rigid head fixation and
      high precision. We report the radiosurgical treatment of five infants by use of a
      robotically controlled system without rigid head fixation. METHODS: Five infants
      with malignant brain tumors received radiosurgical treatment with a robotically
      driven linear accelerator. Immobilization was aided by general anesthesia, form
      fitting head supports, face masks, and body molds. The average marginal dose was
      17 +/- 2 Gy, and the average treatment volume was 18 +/- 22 ml. RESULTS: X-rays
      obtained during treatment revealed acceptable agreement with preoperative
      computed tomographic scans in all patients. In one patient, the lesion did not
      progress, but a distant recurrence occurred 15 months after radiosurgery and also
      was treated with radiosurgery. In another patient, tumor in the treated region
      did not progress, but recurrence elsewhere led to death 7 months after treatment.
      Tumor enlargement occurred in Patient 3 at 3 months posttreatment, leading to
      death 2 months later. Tumor size was smaller in the remaining two patients at 9
      and 11 months after treatment. There has been no toxicity attributed to
      treatment. CONCLUSION: Radiosurgery with minimal toxicity can be delivered to
      infants by use of a robotically controlled system that does not require rigid
      fixation. A formal dose-escalation trial is under way to address dose and
      toxicity for infants more thoroughly.

PMID- 15458601
TI  - Development of hybrid integrated endoscope-holder system for endoscopic
      microneurosurgery.
AB  - OBJECTIVE: Endoscopic techniques in the field of neurosurgery are under
      development. To perform sophisticated bimanual procedures in the delicate
      surgical fields of neurosurgery, rigid endoscope fixation devices with accurate
      locking and a safe releasing system are required. Here, we report the development
      of a new hybrid integrated endoscope-holder system. INSTRUMENTATION: The basic
      concepts of the holding device were as follows: 1) it should combine both video
      system and holding device; 2) it should have easy maneuverability and accurate
      fixation and be equipped with a safe releasing mechanism; and 3) it should be
      able to be used universally either in a primary or an assisting endoscopic
      procedure. A negatively actuated air-locking system and a bayonet-shaped
      endoscope were newly developed. Clinical trials of 25 patients were performed,
      and each prototype was tested and modified until the functional requirements were
      fulfilled. The final version was tested for accuracy and security in fixation and
      releasing mechanism. RESULTS: Eight problems were encountered in the clinical
      trials and improved. Accuracy in fixation of the final version was superior to
      the most advanced endoscope-holder on the market. No dangerous events were
      observed during repetitive insertion, fixation, and release in the simulated deep
      surgical field in the cadaveric skull. No apparent complications were noted in
      the clinical application. CONCLUSION: We have developed a highly reliable,
      accurately fixable, and easily maneuverable hybrid endoscope-holder system. To
      achieve a safer, more accurate, and less invasive surgery in the current
      socioeconomic demands, commercial manufacturers and surgeons in multiple centers
      need to combine their efforts to create useful techniques.

PMID- 15458602
TI  - Endoscopic endonasal transsphenoidal surgery.
AB  - The endoscopic endonasal transsphenoidal approach is a minimally invasive
      surgical technique for the removal of sellar and parasellar lesions. The
      procedure is performed via an anterior sphenoidotomy. The two main
      characteristics of the endoscopic approach, when compared with the standard
      microsurgical operation, arise from the use of the endoscope as a unique optical
      device and from the absence of a transsphenoidal retractor. More convenient
      straight surgical instruments are employed, whereas bayonet-shaped tools are used
      in the microsurgical procedure, to avoid any interference with the light beam
      generated by the microscope. The standard surgical technique is composed of three
      main time phases: the nasal, sphenoid, and sellar phase. During the nasal phase,
      the scope is introduced through the chosen nostril and advanced up to the
      sphenoethmoid recess, where the sphenoidotomy is performed. The sphenoid phase
      consists of the detachment of the nasal septum from the sphenoid rostrum, the
      anterior sphenoidotomy, removal of the sphenoid septum or septa, and
      identification of the landmarks inside the sphenoid sinus. In the sellar phase,
      an opening of the sellar floor is performed for removal of the lesion. A wide
      view of the sellar environment is obtained through angled scopes to detect
      eventual tumor remnants. The procedure ends with the reconstruction of the sella
      and removal of the endoscope from the nostril, without any postoperative nasal
      packing.

PMID- 15458603
TI  - Poloxamer 188 volumetrically decreases neuronal loss in the rat in a time
      dependent manner.
AB  - OBJECTIVE: Excitotoxicity is a multistep process that results in either necrosis
      or apoptosis. It has been associated with neuronal death in trauma, ischemia, and
      neurodegeneration. The final step in necrotic cell death is the rupture of a
      cell's plasma membrane; repair of this membrane rupture is a potentially powerful
      technique of neuroprotection. Poloxamer 188 (P-188) is a synthetic surfactant
      that seals experimentally porated membranes. This study investigated the
      usefulness and time dependence of intrathecal P-188 in protecting neurons in an
      in vivo model of excitotoxicity in the rat. METHODS: Twenty-eight Sprague-Dawley
      rats underwent striatal infusion of quinolinic acid to produce a spherical
      excitotoxic lesion. Each animal then received either vehicle or P-188 at 10
      minutes, 4 hours, or both time points after surgery by direct cisterna magna
      injection. Animals were killed at 1 week, and brains were stained
      immunohistochemically for the neuronal marker Neu-N. Volumes of neuronal loss
      were calculated and compared between groups by analysis of variance. RESULTS: All
      animals were found to have spherical, stereotyped lesions. The animals that
      received intrathecal poloxamer at the early injection time had statistically
      smaller lesions (8.16 +/- 6.12 mm(3); n = 5; P = 0.0015) than controls (18.25 +/-
      11.42 mm(3); n = 11). Those animals that received poloxamer at both injection
      times also had statistically smaller lesions (10.57 +/- 9.00 mm(3); n = 7; P =
      0.0095). The group that received poloxamer at the late injection time only did
      not have significantly decreased lesion size (14.86 +/- 7.95 mm(3); n = 5).
      CONCLUSION: Intrathecal P-188 reduces neuronal loss after excitotoxic injury in
      the rat only when delivered immediately after the toxin. This observation
      confirms the potential of surfactant molecules as neuroprotectants but predicts
      that their usefulness is best realized by early and potentially ongoing
      treatment.

PMID- 15458604
TI  - Suturing technique and the integrity of dural closures: an in vitro study.
AB  - OBJECTIVE: The watertight closure of the dura mater is fundamental to
      intracranial procedures in neurosurgery. Nevertheless, for any given operator and
      type of suture, it is still not certain which suturing technique affords the most
      watertight dural closure. We have developed a laboratory model that allows us to
      compare the pressures at which dural closures leak when different suturing
      techniques are used. METHODS: Human cadaveric dura was secured to a glass
      cylinder filled with colored saline. By application of force to a bag of saline
      attached to the cylinder, the pressure at which sutured dural incisions leak can
      be recorded. Using this method, we have compared the closure of 2-cm dural
      incisions with 3-0 silk using the following techniques (10 per group): 1)
      interrupted simple, 2) running simple, 3) running locked, and 4) interrupted
      vertical mattress. We have also compared the closure of 1- x 3-cm dural windows
      with cadaveric dura and 3-0 silk using the same suturing techniques (10 per
      group). RESULTS: The pressure at which 2-cm linear dural incisions leaked was
      significantly higher when they were closed with the interrupted simple suturing
      technique (P < 0.05). There was no significant difference among the different
      suturing techniques when they were used to close a 1- x 3-cm dural window with a
      duraplasty. Overall, the pressures at which sutured linear dural incisions leaked
      were higher than the pressures at which sutured dural windows closed with
      duraplasties leaked. CONCLUSION: In the experimental model described, an
      interrupted simple suturing technique affords the most watertight dural closure
      for linear incisions, whereas no suturing technique proved advantageous for the
      closure of a duraplasty.

PMID- 15458605
TI  - The science and design of head protection in sport.
AB  - We review the relationship between science, testing standards, and helmet design
      to provide an understanding of how helmets protect the brain. Research describing
      the mechanisms of injury, resulting types of brain injuries, and characteristics
      of helmet protection are reviewed. The article is designed to describe the state
      of the relationship between science and helmet performance.

PMID- 15458606
TI  - One man's recollection of 50 years of functional and stereotactic neurosurgery.
AB  - The author summarizes personal recollections of his training and career in
      stereotactic and functional neurosurgery from the 1950s until his retirement from
      active surgery in 1999.

PMID- 15458607
TI  - Possible oncogenicity of subventricular zone neural stem cells: case report.
AB  - OBJECTIVE: The origin of brain tumors has attracted much controversy. Recent
      advances in neural stem cell biology coupled with the new concepts of central
      nervous system development have raised interesting possibilities regarding the
      oncogenic properties of neural stem/progenitor cells. To elucidate these putative
      properties further, the clinical materials from an infant brain tumor were
      analyzed, focusing on the relation with the neural stem/progenitor cells.
      METHODS: The expression of neural stem/progenitor cell markers in the tumor cells
      and the cellular components of the infant brain tumor were examined using
      immunohistochemistry. The tumor cell biology was analyzed both in culture and in
      the grafted brain environment. RESULTS: Three main bodies of evidence were
      demonstrated indicating that the tumor was of possible subventricular zone
      postnatal or adult normal neural stem cell origin. First, in the tumor specimen
      we demonstrated the strong positive expression of the neural stem/progenitor cell
      markers, nestin and Musashi-1. Second, immunohistochemistry revealed the presence
      of neuronal, astrocytic, and immature precursor cells in the tumor tissue,
      similar to the cellular components of the subventricular zone, thereby pointing
      to the subventricular zone as the possible origin of the tumor. The
      subventricular zone also is one of the strong candidates for the location of
      postnatal/adult neural stem cells. This cellular evidence was strengthened
      further by the clinicoradiological findings that demonstrated the involvement of
      the subventricular zone of the lateral ventricle by the tumor. Third, in the in
      vitro and in vivo experiments, a dynamic shift in expression patterns between
      neural stem cells (nestin, Musashi-1) and differentiated cells (glial fibrillary
      acidic protein, neuron-specific Class III beta-tubulin) markers was seen, similar
      to the proposed behavior of postnatal/adult neural stem cells in situ.
      CONCLUSION: These findings suggest that this brain tumor originated from neural
      stem cells located in the subventricular zone, and the further possibility of the
      general oncogenic potential of neural stem cells.

PMID- 15458608
TI  - The legacy of Pompeii and its volcano.
AB  - On August 24, AD 79, a terrible eruption of Mount Vesuvius deranged life in
      beautiful Pompeii and killed thousands of men, women, and children. They were
      restored to us by the fact that Mount Vesuvius, with its rain of ashes, proved to
      be a skilled sculptor, preserving the shape and even the wrinkles in the clothes
      the Pompeians wore while trying to escape during the day of the tragedy. The
      detailed description of Plinius the Younger and modern static studies of the
      eruptive residues have made it possible to reconstruct with great accuracy the
      various phases of the eruption that took place 2000 years ago, including the
      hours and days during which the phenomena first became obvious. Today, almost
      2000 years later, Pompeii has reawakened and risen from its sepulcher of ashes
      thanks to the excavations initiated under King Charles III of Bourbon in 1748.
      Excavations proceeded slowly under the Bourbons, with the aim of enriching the
      Bourbon Museum of Naples rather than of classifying the ruins and placing them
      into a historical context. Under Joachim Murat, interest in the town planning and
      architecture of the uncovered cities reemerged, especially with respect to
      Pompeii. In 1860, however, with the establishment of the Kingdom of Italy, the
      excavations, now under the direction of archaeologist Giuseppe Fiorelli, were
      provided new impetus and, finally, a scientific basis. Today, the excavations are
      giving us back extraordinary evidence concerning the culture, the everyday life,
      the habits, the architecture, and the wonderful frescoes of the Roman cities of
      southern Italy, making possible the statement that Pompeii is "the most alive of
      the dead cities."

PMID- 15458609
TI  - Sildenafil-induced relapse in bipolar disorder: is nitric oxide the mechanism?

PMID- 15458610
TI  - A review of the evidence for carbamazepine and oxcarbazepine in the treatment of
      bipolar disorder.
AB  - Bipolar disorder is a recurrent lifelong condition associated with significant
      morbidity and mortality. The main goals of treatment are the acute management of
      manic/depressive episodes and the prevention of recurrence. Mood stabilizers are
      the basis of most treatment regimens. Although lithium is the classical mood
      stabilizer, dissatisfaction with its efficacy and tolerability has led to
      increased use of other mood- stabilizing agents, including anticonvulsants. Newer
      anticonvulsants such as oxcarbazepine may offer improved tolerability and fewer
      drug-drug interactions compared to older drugs like carbamazepine. A search of
      the literature shows that data from controlled clinical studies support the
      efficacy of carbamazepine in treating acute mania and as maintenance therapy. In
      addition, a growing body of data for oxcarbazepine suggests that this newer agent
      may have a similar efficacy profile to carbamazepine, with improved tolerability.
      This review presents a balanced selection of the key studies on carbamazepine and
      oxcarbazepine in bipolar disorder.

PMID- 15458611
TI  - The C(-1019)G polymorphism of the 5-HT1A gene promoter and antidepressant
      response in mood disorders: preliminary findings.
AB  - Several studies have demonstrated the involvement of 5-HT1A receptors in the
      pathogenesis of depression and in the antidepressant response to SSRIs. A
      functional new variant in the promoter region of the 5-HT1A gene was recently
      reported (-1019 C>G). The aim of this study is to investigate a possible
      association between this 5-HT1A receptor variant and antidepressant response to
      fluvoxamine in a sample of 262 mood-disorder subjects (151 major depressed and
      111 bipolars) treated with fluvoxamine for 6 wk. The severity of depressive
      symptoms was assessed weekly with the Hamilton Rating Scale for Depression
      (HAMD). 5-HT1A variants did not influence antidepressant response in the whole
      sample and in unipolar subjects. In bipolars, 5-HT1A*C/C genotype carriers showed
      a better response to fluvoxamine (p=0.036), independently from clinical
      variables. The 5-HT1A polymorphism effect on antidepressant response was
      independent from the previously reported effect of the 5-HTTLPR polymorphism. In
      conclusion, 5-HT1A variants could influence the antidepressant efficacy in
      bipolar subjects, even if results must be verified on larger samples.

PMID- 15458612
TI  - Hypericum extract in patients with MDD and reversed vegetative signs: re-analysis
      from data of a double-blind, randomized trial of hypericum extract, fluoxetine,
      and placebo.
AB  - Hypericum extract (HE) might be favourably active in depressed patients with
      reversed vegetative signs (RVS). Therefore, we performed an exploratory subgroup
      analysis of a three-armed study to compare HE, fluoxetine, and placebo in
      patients with major depressive disorder (MDD) in a 12 wk trial. A total of 135
      patients were randomized to 12 wk treatment with HE LI 160 (900 mg/d), fluoxetine
      (20 mg/d), or placebo. Patients with RVS were defined in two steps, according to
      DSM-IV. First, patients with melancholy-related vegetative signs were excluded.
      Secondly, patients had to have at least one score of 2 for the items 22-26 of the
      HAMD-28 scale, which are related to hypersomnia and hyperphagia. Twenty-seven
      patients remained in the group. Analysis of covariance (ANCOVA) was applied using
      the HAMD-17 score. Secondly a chi2 test for response was performed, using the
      same and further an adapted criterium as in recently published studies. ANCOVA
      revealed a trend to a global difference. Post-hoc analysis showed a trend to
      superiority of HE compared to placebo and to fluoxetine, but a very large effect
      size for both differences. Fluoxetine was not different from placebo. The adapted
      response criterium showed a significant global difference as well as a
      significant superiority of HE over placebo and over fluoxetine. These data are
      based on a small sample size and must be considered tentative. A characterization
      of vegetative features of patients with depression could lead to an overall
      increased effect size in the treatment with HE.

PMID- 15458613
TI  - [Are environmental controls effective for house-dust-mite allergies?].

PMID- 15458614
TI  - [Bacterial colonization and home mechanical ventilation: prevalence and risk
      factors].
AB  - OBJECTIVE: To investigate the prevalence of bacterial contamination of
      ventilators and colonization of patients, the bacteria implicated, and
      predisposing factors in noninvasive home ventilation. MATERIAL AND METHODS: Forty
      patients on a home noninvasive ventilation program (mean [SD] age: 63.1 [12]
      years; time on ventilation: 30.7 [25] months; daily use: 8.1 [2] hours) were
      enrolled in this descriptive cross-sectional study. Microbiological samples for
      semiquantitative cultures were swabbed from the ventilator (mask and tubing) and
      the nostrils. A questionnaire was completed on the underlying disease, time on
      the ventilation program, type of ventilator, presence of a humidifier, and
      attention to ventilator cleanliness and maintenance. We defined "colonization" as
      the presence of microorganisms in the nostrils without evidence of a host immune
      response, and "contamination" as the presence of surface microorganisms (on
      tubing or the nasal mask). RESULTS: Potentially pathogenic bacteria were isolated
      from 6 ventilators (15%) and the nasal swabs of 10 patients (25%). Staphylococcus
      aureus was the most frequently isolated one (in 5 ventilators and 6 patients-
      contamination coinciding with colonization in 3 cases). Other potentially
      pathogenic bacteria isolated were Proteus species (from the nostrils of 2
      patients) and an unidentified gram-negative bacillus from the ventilator. On
      analysis by underlying disease, 60% of the patients with obesity had been
      colonized. No other findings of note were obtained for other diseases.
      Contamination and colonization correlated with attention to cleanliness and
      maintenance of the ventilator but not with type of ventilator, time on the
      ventilation program, or use of a humidifier. CONCLUSIONS: Home mechanical
      ventilators are a potential source of nasal colonization. The most frequently
      encountered microorganism was S. aureus. The degree of ventilator cleaning and
      disinfection seems to affect contamination; thus it is necessary to impress on
      patients the need for adequate maintenance of their ventilators.

PMID- 15458615
TI  - [Association between the forced midexpiratory flow/forced vital capacity ratio
      and bronchial hyperresponsiveness].
AB  - OBJECTIVE: A long-standing hypothesis is that a low ratio of airway caliber to
      lung size is associated with bronchial hyperresponsiveness (BHR). The aim of our
      study was to measure the association between airway caliber relative to lung size
      (expressed as the ratio between forced expiratory flow, midexpiratory phase,
      divided by forced vital capacity [FEF(25%-75%)/FVC]) and BHR measured by a
      methacholine challenge test, adjusting for age, height, sex, smoking history,
      geographic area, respiratory symptoms, and baseline forced expiratory volume in 1
      second (FEV1). MATERIAL AND METHODS: We carried out a multicenter cross-sectional
      study of the general Spanish population in 2647 subjects from the European
      Community Respiratory Health Survey (ECRHS I). The ECRHS questionnaire was
      administered, total and specific immunoglobulin E were measured, and skin tests,
      spirometry, and a methacholine challenge test were performed. RESULTS: We show
      the relationship of the various clinical and sociodemographic variables with the
      2 parameters indicative of a positive methacholine test. The lower the FEF(25%
      75%)/FVC ratio was, the greater the risk of HRB, after adjustment for variables
      (odds ratio [OR]=0.09; 95% confidence interval [CI], 0.04-0.018 for the
      concentration provoking a 20% decrease in FEV1, and OR=0.06; 95% CI, 0.03-0.12
      for the dose provoking a 20% decrease in FEV1). CONCLUSIONS: There is a
      significant association between the FEF(25%-75%)/FVC ratio and BHR after
      adjustment for age, atopy, smoking, geographic area, respiratory symptoms, and
      initial FEV1.

PMID- 15458616
TI  - [Smoking habits among sixth-year medical students in Spain].
AB  - OBJECTIVE: To describe and analyze the smoking habits of sixth-year Spanish
      medical students. MATERIAL AND METHODS: The target population of this descriptive
      cross-sectional study was students completing their sixth year in Spanish medical
      schools. An anonymous, self-administered questionnaire was sent to the students'
      homes by ordinary mail. The relationships between the variables were analyzed
      using contingency tables, the chi2 test, the Student t test, and analysis of
      variance with a significance level of P< .05. The software package was SPSS.
      RESULTS: A total of 3840 questionnaires were distributed to students, and 1340
      were returned completed (34.9%). Of the respondents, 27% were smokers (8.7%
      smoked only on weekends, and 18.3% were daily smokers). The mean (SD) number of
      cigarettes smoked per day was 10.54 (7.89). Consumption was significantly higher
      among men than among women. The mean age of initiation was 17.20 years. Of the
      students who were smokers, 32.54% stated that they had started smoking during
      their medical studies. The percentage of smokers who stated that they wanted to
      quit was 76.3%, and 56.6% said that they had already made at least one quit
      attempt. CONCLUSIONS: It is cause for concern that a large number of students
      start smoking after they enter medical school. One of the reasons for this is the
      lack of concern about smoking as a health problem within medical schools. The
      smoking habits of medical students are affected by the same phenomena that affect
      those of the general public, such as the increase in the number of women smokers,
      the influence of sociocultural factors, and the increasingly broader age range of
      initiation. The lower prevalence of smoking among medical students with respect
      to other populations is probably due to the fact that, in general, these students
      have better health habits than the general public, and/or the reasons that led
      them to study medicine also make them disinclined to smoke.

PMID- 15458617
TI  - [Video-assisted thoracoscopic thymectomy for the treatment of myasthenia gravis].
AB  - OBJECTIVE: Traditionally, thymectomy for myasthenia gravis has been performed
      using either a transcervical approach or a median sternotomy. However, excision
      of the thymic tissue by video-assisted thoracoscopic surgery is less aggressive
      and recovery is faster. The aim of this study was to evaluate the usefulness and
      outcomes of video-assisted thoracoscopic thymectomy. PATIENTS AND METHODS: Over
      the past 10 years, we have performed 25 video-assisted thoracoscopic thymectomies
      on patients with myasthenia gravis at our unit. This study included 16 women and
      9 men, with a mean age of 48.1 years (range, 14-74 years). Right-side (22 cases)
      or left-side (3 cases) thoracoscopic surgery was performed, with a mean
      intervention time of 110 minutes (range, 60-193 minutes). RESULTS: No patient
      required assisted ventilation for more than 4 hours and the maximum stay in
      intensive care was less than 24 hours. Complications from surgery included 3
      cases of contralateral pneumothorax, 1 pleural effusion, and 2 intraoperative
      hemorrhages from the thymic vein, all of which were resolved by video-assisted
      thoracoscopy. Likewise, 3 cases required conversion (due to hemorrhaging in 2
      patients and technical difficulties in 1) and 2 required a second thoracoscopic
      intervention. No deaths occurred and clinical outcome was excellent in 11 cases
      (medical treatment no longer required), good in 10 (reduced medical treatment),
      and poor in 4 (no changes). CONCLUSIONS: Video-assisted thoracoscopic thymectomy
      is effective in the treatment of myasthenia gravis and improves patient recovery.
      In addition, the excellent surgical view allows the thymectomy to be performed
      with absolute safety.

PMID- 15458618
TI  - [Asthma and tobacco smoke].

PMID- 15458619
TI  - [Localized fibrous tumors of the pleura: clinical and surgical evaluation].
AB  - Solitary fibrous tumors of the pleura are uncommon and mainly arise in the pleura
      itself. Such tumors are generally asymptomatic and slow-growing. We report a
      series of 10 cases (8 men and 2 women with a mean age of 58.6 years) treated over
      a period of 54 months. The tumors were classified histologically as benign or
      malignant according to the criteria used by England. The treatment of choice was
      complete resection of the tumor. Six posterolateral thoracotomies and 4 video
      assisted resections were performed. Histology showed a mixture of fibroblast-like
      cells and collagenous stroma. Sarcomatous degeneration was observed in the
      excised tumor of 1 patient. The patients were followed for a mean of 23.9 months.
      We conclude that although fibrous tumors of the pleura are considered benign
      histologically, complete resection and follow up for all patients are
      recommended.

PMID- 15458620
TI  - [Pneumocephalus and cerebrospinal fluid fistula following removal of a superior
      sulcus tumor (pancoast tumor)].
AB  - Pneumocephalus resulting from a subarachnoid-pleural fistula following resection
      of a pulmonary neoplasm is a very rare postoperative complication: we have found
      only 17 cases in the literature. We report the case of a 65-year-old man
      diagnosed with a superior sulcus tumor who underwent a left upper lobectomy and
      costal resection following neoadjuvant radiation therapy. Soon after surgery, the
      patient developed a subarachnoid-pleural fistula and pneumocephalus that required
      reoperation and drainage. Recurrence was suspected when chronic aseptic
      meningitis developed. Another thoracotomy was required to resolve the
      complication.

PMID- 15458621
TI  - [Langerhans-cell histiocytosis of 28-year evolution].

PMID- 15458622
TI  - [Pulmonary mucinous tumor of low malignancy].

PMID- 15458623
TI  - Infidelity out in the open.
AB  - The crystal structures of DNA polymerase beta in complex with two different
      mispairs (A-C and T-C) reveal that the two bases stack partially, rather than
      engage in hydrogen bonding with each other (Krahn et al., this issue of
      Structure). The N-domain of the polymerase, which is closed when the correct
      nucleotide pairs with the template base, adopts a partially open conformation
      suboptimal for catalysis.

PMID- 15458624
TI  - Protein folding: simple models for a complex process.
AB  - Twenty-eight years after its original publication, the diffusion-collision model
      has successfully been applied to describe the folding kinetics of two proteins
      with the same native structure but different sequences (Islam et al., this issue
      of Structure). The calculations show the relative importance of the primary and
      tertiary structure on the sequence of events and folding. For both proteins, the
      model suggests parallel folding pathways, a finding which has wide implications
      for the interpretations of experiments.

PMID- 15458625
TI  - CRANK: new methods for automated macromolecular crystal structure solution.
AB  - CRANK is a novel suite for automated macromolecular structure solution and uses
      recently developed programs for substructure detection, refinement, and phasing.
      CRANK utilizes methods for substructure detection and phasing and combines them
      with existing crystallographic programs for density modification and automated
      model building in a convenient and easy-to-use CCP4i graphical interface. The
      data model used conforms to the XML eXtensible Markup Language specification and
      works as a common language to communicate data between many different
      applications inside and outside of the suite. The application of CRANK on various
      test cases has yielded promising results: with minimal user input, CRANK can
      produce better quality solutions over currently available programs.

PMID- 15458626
TI  - Methods for generating high-resolution structural models from electron microscope
      tomography data.
AB  - Reconstructed volumes generated by tilt-image electron-microscope tomography
      offer the best spatial resolution currently available for studying cell
      structures in situ. Analysis is often accomplished by creating surface models
      that delineate grayscale contrast boundaries. Here, we introduce a specialized
      and convenient sequence of segmentation operations for making such models that
      greatly improves their reliability and spatial resolution as compared to current
      approaches, providing a basis for making accurate measurements. To assess the
      reliability of the surface models, we introduce a spatial uncertainty measurement
      based on grayscale gradient scale length. The model generation and measurement
      methods are validated by applying them to synthetic data, and their utility is
      demonstrated by using them to characterize macromolecular architecture of active
      zone material at the frog's neuromuscular junction.

PMID- 15458627
TI  - Mechanisms of coupling between DNA recognition specificity and catalysis in EcoRI
      endonuclease.
AB  - Proteins that bind to specific sites on DNA often do so in order to carry out
      catalysis or specific protein-protein interaction while bound to the recognition
      site. Functional specificity is enhanced if this second function is coupled to
      correct DNA site recognition. To analyze the structural and energetic basis of
      coupling between recognition and catalysis in EcoRI endonuclease, we have studied
      stereospecific phosphorothioate (PS) or methylphosphonate (PMe) substitutions at
      the scissile phosphate GpAATTC or at the adjacent phosphate GApATTC in
      combination with molecular-dynamics simulations of the catalytic center with
      bound Mg2+. The results show the roles in catalysis of individual phosphoryl
      oxygens and of DNA distortion and suggest that a "crosstalk ring" in the complex
      couples recognition to catalysis and couples the two catalytic sites to each
      other.

PMID- 15458628
TI  - Three-dimensional structure of the intact Thermus thermophilus H+-ATPase/synthase
      by electron microscopy.
AB  - ATPases are unique rotary motors that are essential to all living organisms
      because of their role in energy interconversion. A three-dimensional
      reconstruction of the intact H+-ATPase/synthase from Thermus thermophilus has
      revealed the presence of two interconnected peripheral stalks, a well-defined
      central stalk, and a hexagonally shaped hydrophobic domain. The peripheral stalks
      are each attached to the water soluble sector at a noncatalytic subunit interface
      and extend down toward the membrane where they interact with a strong elongated
      tube of density that runs parallel to the membrane and connects the two stalks.
      The central stalk is well resolved, especially with respect to its interaction
      with a single catalytic subunit giving rise to an asymmetry comparable to that
      identified in F-ATPases. The hexagonal shape of the membrane domain might suggest
      the presence of 12 proteolipids arranged as dimers, analogous to the proposed
      arrangement in the related eukaryotic V-ATPases.

PMID- 15458629
TI  - Flipping the switch from monomeric to dimeric CV-N has little effect on antiviral
      activity.
AB  - Cyanovirin-N can exist in solution in monomeric and domain-swapped dimeric forms,
      with HIV-antiviral activity being reported for both. Here we present results for
      CV-N variants that form stable solution dimers: the obligate dimer [DeltaQ50]CV-N
      and the preferential dimer [S52P]CV-N. These variants exhibit comparable DeltaG
      values (10.6 +/- 0.5 and 9.4 +/- 0.5 kcal.mol(-1), respectively), similar to that
      of stabilized, monomeric [P51G]CV-N (9.8 +/- 0.5 kcal.mol(-1)), but significantly
      higher than wild-type CV-N (4.1 +/- 0.2 kcal.mol(-1)). During folding/unfolding,
      no stably folded monomer was observed under any condition for the obligate dimer
      [DeltaQ50]CV-N, whereas two monomeric, metastable species were detected for
      [S52P]CV-N at low concentrations. This is in contrast to our previous results for
      [P51G]CV-N and wild-type CV-N, for which the dimeric forms were found to be the
      metastable species. The dimeric mutants exhibit comparable antiviral activity
      against HIV and Ebola, similar to that of wild-type CV-N and the stabilized
      [P51G]CV-N variant.

PMID- 15458630
TI  - Crystal structure of an aminoimidazole riboside kinase from Salmonella enterica:
      implications for the evolution of the ribokinase superfamily.
AB  - The crystal structures of a Salmonella enterica aminoimidazole riboside (AIRs)
      kinase, its complex with the substrate AIRs, and its complex with AIRs and an ATP
      analog were determined at 2.6 angstroms, 2.9 angstroms, and 2.7 angstroms,
      respectively. The product of the Salmonella-specific gene stm4066, AIRs kinase,
      is a homodimer with one active site per monomer. The core structure, consisting
      of an eight-stranded beta sheet flanked by eight alpha helices, indicates that
      AIRs kinase is a member of the ribokinase superfamily. Unlike ribokinase and
      adenosine kinase in this superfamily, AIRs kinase does not show significant
      conformational changes upon substrate binding. The active site is covered by a
      lid formed by residues 16-28 and 86-100. A comparison of the structure of AIRs
      kinase with other ribokinase superfamily members suggests that the active site
      lid and conformational changes that occur upon substrate binding may be advanced
      features in the evolution of the ribokinase superfamily.

PMID- 15458631
TI  - Structural insights into DNA polymerase beta deterrents for misincorporation
      support an induced-fit mechanism for fidelity.
AB  - DNA polymerases generally select the correct nucleotide from a pool of
      structurally similar molecules to preserve Watson-Crick base-pairing rules. We
      report the structure of DNA polymerase beta with DNA mismatches situated in the
      polymerase active site. This was achieved by using nicked product DNA that traps
      the mispair (template-primer, A-C or T-C) in the nascent base pair binding
      pocket. The structure of each mispair complex indicates that the bases do not
      form hydrogen bonds with one another, but form a staggered arrangement where the
      bases of the mispair partially overlap. This prevents closure/opening of the N
      subdomain that is believed to be required for catalytic cycling. The partially
      open conformation of the N subdomain results in distinct hydrogen bonding
      networks that are unique for each mispair. These structures define diverse
      molecular aspects of misinsertion that are consistent with the induced-fit model
      for substrate specificity.

PMID- 15458632
TI  - The role of sequence and structure in protein folding kinetics; the diffusion
      collision model applied to proteins L and G.
AB  - The diffusion-collision model (DCM) is applied to the folding kinetics of protein
      L and protein G. In the DCM, the two proteins are treated as consisting of two
      beta-hairpins and one alpha-helix, so that they are isomorphous with the three
      helix bundle DCM model. In the absence of sequence dependent factors, both
      proteins would fold in the same way in the DCM, with the coalescence of the N
      terminal hairpin and the helix slightly favored over the C-terminal hairpin and
      the helix because the former are closer together than the latter. However,
      sequence dependent factors make the N-terminal hairpin of protein L and the C
      terminal hairpin of protein G more stable in the ensemble of unfolded
      conformations. This difference in the stabilities gives rise to the difference in
      the calculated folding behavior, in agreement with experiment.

PMID- 15458633
TI  - Anatomy of an amyloidogenic intermediate: conversion of beta-sheet to alpha-sheet
      structure in transthyretin at acidic pH.
AB  - The homotetramer of transthyretin (TTR) dissociates into a monomeric
      amyloidogenic intermediate that self-assembles into amyloid fibrils at low pH. We
      have performed molecular dynamics simulations of monomeric TTR at neutral and low
      pH at physiological (310 K) and very elevated temperature (498 K). In the low-pH
      simulations at both temperatures, one of the two beta-sheets (strands CBEF)
      becomes disrupted, and alpha-sheet structure forms in the other sheet (strands
      DAGH). alpha-sheet is formed by alternating alphaL and alphaR residues, and it
      was first proposed by Pauling and Corey. Overall, the simulations are in
      agreement with the available experimental observations, including solid-state NMR
      results for a TTR-peptide amyloid. In addition, they provide a unique explanation
      for the results of hydrogen exchange experiments of the amyloidogenic
      intermediate-results that are difficult to explain with beta-structure. We
      propose that alpha-sheet may represent a key pathological conformation during
      amyloidogenesis.

PMID- 15458634
TI  - The crystal structure of the actIII actinorhodin polyketide reductase: proposed
      mechanism for ACP and polyketide binding.
AB  - We have determined the 2.5 angstroms crystal structure of an active, tetrameric
      Streptomyces coelicolor type II polyketide ketoreductase (actIII) with its bound
      cofactor, NADP+. This structure shows a Rossman dinucleotide binding fold
      characteristic of SDR enzymes. Of two subunits in the crystallographic asymmetric
      unit, one is closed around the active site. Formate is observed in the open
      subunit, indicating possible carbonyl binding sites of the polyketide
      intermediate. Unlike previous models we observe crystal contacts that may mimic
      the KR-ACP interactions that may drive active site opening. Based on these
      observations, we have constructed a model for ACP and polyketide binding. We
      propose that binding of ACP triggers a conformational change from the closed to
      the open, active form of the enzyme. The polyketide chain enters the active site
      and reduction occurs. The model also suggests a general mechanism for ACP
      recognition which is applicable to a range of protein families.

PMID- 15458635
TI  - Prediction of multiple tandem OB-fold domains in telomere end-binding proteins
      Pot1 and Cdc13.
AB  - The heterodimeric Oxytricha nova telomere end binding protein, the original
      telomere end binding protein characterized, contains four OB-fold domains used
      for recognition of single-stranded telomeric DNA. In contrast, only solitary OB
      fold domains have been found in the telomere end binding proteins from yeast and
      higher eukaryotes. Using a sliding-window algorithm coupled with sequence profile
      profile analysis, we provide support for the existence of multiple OB-fold
      domains in two other telomeric ssDNA binding proteins, vertebrate Pot1 and
      budding yeast Cdc13. This common usage of multiple, tandem OB-fold domains in
      telomeric end binding proteins extends the known evolutionary conservation of
      eukaryotic end-protection mechanisms.

PMID- 15458636
TI  - A novel structure of DNA repair protein RecO from Deinococcus radiodurans.
AB  - Recovery of arrested replication requires coordinated action of DNA repair,
      replication, and recombination machineries. Bacterial RecO protein is a member of
      RecF recombination repair pathway important for replication recovery. RecO
      possesses two distinct activities in vitro, closely resembling those of
      eukaryotic protein Rad52: DNA annealing and RecA-mediated DNA recombination. Here
      we present the crystal structure of the RecO protein from the extremely radiation
      resistant bacteria Deinococcus radiodurans (DrRecO) and characterize its DNA
      binding and strand annealing properties. The RecO structure is totally different
      from the Rad52 structure. DrRecO is comprised of three structural domains: an N
      terminal domain which adopts an OB-fold, a novel alpha-helical domain, and an
      unusual zinc-binding domain. Sequence alignments suggest that the multidomain
      architecture is conserved between RecO proteins from other bacterial species and
      is suitable to elucidate sites of protein-protein and DNA-protein interactions
      necessary for RecO functions during the replication recovery and DNA repair.

PMID- 15458637
TI  - Crystal structure of the TAO2 kinase domain: activation and specificity of a
      Ste20p MAP3K.
AB  - TAO2 is a mitogen-activated protein kinase kinase kinase (MAP3K) that doubly
      phosphorylates and activates the MAP kinase kinases (MAP2Ks) MEK3 and MEK6. The
      structure of the kinase domain of TAO2 (1-320) has been solved in its
      phosphorylated active conformation. The structure, together with structure-based
      mutagenic analysis, reveals that positively charged residues in the substrate
      binding groove mediate the first step in the dual phosphorylation of MEK6, on the
      threonine residue in the motif DS*VAKT*I (*denotes phosphorylation site) of MEK6.
      TAO2 is a Ste20p homolog, and the structure of active TAO2, in comparison with
      that of low-activity p21-activated protein kinase (PAK1), a Ste20p-related MAP4K,
      reveals how this group of kinases is activated by phosphorylation. Finally,
      active TAO2 displays unusual interactions with ATP, involving, in part, a
      subgroup-specific C-terminal extension of TAO2. The observed interactions may be
      useful in making specific inhibitors of TAO kinases.

PMID- 15458638
TI  - The crystal structure of the reduced, Zn2+-bound form of the B. subtilis Hsp33
      chaperone and its implications for the activation mechanism.
AB  - The bacterial heat shock protein Hsp33 is a redox-regulated chaperone activated
      by oxidative stress. In response to oxidation, four cysteines within a Zn2+
      binding C-terminal domain form two disulfide bonds with concomitant release of
      the metal. This leads to the formation of the biologically active Hsp33 dimer.
      The crystal structure of the N-terminal domain of the E. coli protein has been
      reported, but neither the structure of the Zn2+ binding motif nor the nature of
      its regulatory interaction with the rest of the protein are known. Here we report
      the crystal structure of the full-length B. subtilis Hsp33 in the reduced form.
      The structure of the N-terminal, dimerization domain is similar to that of the E.
      coli protein, although there is no domain swapping. The Zn2+ binding domain is
      clearly resolved showing the details of the tetrahedral coordination of Zn2+ by
      four thiolates. We propose a structure-based activation pathway for Hsp33.

PMID- 15458639
TI  - Structural dynamics of the M4 transmembrane segment during acetylcholine receptor
      gating.
AB  - The transition state structures that link the stable end states of allosteric
      proteins are largely unresolved. We used single-molecule kinetic analysis to
      probe the dynamics of the M4 transmembrane segments during the closed<==>open
      isomerization of the neuromuscular acetylcholine receptor ion channel (AChR). We
      measured the slopes (phi) of the free energy relationships for 87 mutants, which
      reveal the open- versus closed-like characters of the mutated residues at the
      transition state and hence the sequence and organization of gating molecular
      motions. phi was constant throughout the length of the alpha subunit M4 segment
      with an average value of 0.54, suggesting that this domain moves as a unit,
      approximately midway through the reaction. Analysis of a hybrid construct
      indicates that the two alpha subunits move synchronously. Between subunits, the
      sequence of M4 motions is alpha-epsilon-beta. The AChR ion channel emerges as a
      dynamic nanomachine with many moving parts.

PMID- 15458640
TI  - Drosophila T box proteins break the symmetry of hedgehog-dependent activation of
      wingless.
AB  - BACKGROUND: Segmentation of the Drosophila embryo is a classic paradigm for
      pattern formation during development. The Wnt-1 homolog Wingless (Wg) is a key
      player in the establishment of a segmentally reiterated pattern of cell type
      specification. The intrasegmental polarity of this pattern depends on the precise
      positioning of the Wg signaling source anterior to the Engrailed (En)/Hedgehog
      (Hh) domain. Proper polarity of epidermal segments requires an asymmetric
      response to the bidirectional Hh signal: wg is activated in cells anterior to the
      Hh signaling source and is restricted from cells posterior to this signaling
      source. RESULTS: Here we report that Midline (Mid) and H15, two highly related T
      box proteins representing the orthologs of zebrafish hrT and mouse Tbx20, are
      novel negative regulators of wg transcription and act to break the symmetry of Hh
      signaling. Loss of mid and H15 results in the symmetric outcome of Hh signaling:
      the establishment of wg domains anterior and posterior to the signaling source
      predominantly, but not exclusively, in odd-numbered segments. Accordingly, loss
      of mid and H15 produces defects that mimic a wg gain-of-function phenotype.
      Misexpression of mid represses wg and produces a weak/moderate wg loss-of
      function phenocopy. Furthermore, we show that loss of mid and H15 results in an
      anterior expansion of the expression of serrate (ser) in every segment,
      representing a second instance of target gene repression downstream of Hh
      signaling in the establishment of segment polarity. CONCLUSIONS: The data we
      present here indicate that mid and H15 are important components in pattern
      formation in the ventral epidermis. In odd-numbered abdominal segments, Mid/H15
      activity plays an important role in restricting the expression of Wg to a single
      domain.

PMID- 15458642
TI  - Roles of polo-like kinase 1 in the assembly of functional mitotic spindles.
AB  - BACKGROUND: The stable association of chromosomes with both poles of the mitotic
      spindle (biorientation) depends on spindle pulling forces. These forces create
      tension across sister kinetochores and are thought to stabilize microtubule
      kinetochore interactions and to silence the spindle checkpoint. Polo-like kinase
      1 (Plk1) has been implicated in regulating centrosome maturation, mitotic entry,
      sister chromatid cohesion, the anaphase-promoting complex/cyclosome (APC/C), and
      cytokinesis, but it is unknown if Plk1 controls chromosome biorientation.
      RESULTS: We have analyzed Plk1 functions in synchronized mammalian cells by RNA
      interference (RNAi). Plk1-depleted cells enter mitosis after a short delay,
      accumulate in a preanaphase state, and subsequently often die by apoptosis.
      Spindles in Plk1-depleted cells lack focused poles and are not associated with
      centrosomes. Chromosomes attach to these spindles, but the checkpoint proteins
      Mad2, BubR1, and CENP-E are enriched at many kinetochores. When Plk1-depleted
      cells are treated with the Aurora B inhibitor Hesperadin, which silences the
      spindle checkpoint by stabilizing microtubule-kinetochore interactions, cells
      degrade APC/C substrates and exit mitosis without chromosome segregation and
      cytokinesis. Experiments with monopolar spindles that are induced by the kinesin
      inhibitor Monastrol indicate that Plk1 is required for the assembly of spindles
      that are able to generate poleward pulling forces. CONCLUSIONS: Our results imply
      that Plk1 is not essential for mitotic entry and APC/C activation but is required
      for proper spindle assembly and function. In Plk1-depleted cells spindles may not
      be able to create enough tension across sister kinetochores to stabilize
      microtubule-kinetochore interactions and to silence the spindle checkpoint.

PMID- 15458641
TI  - Distribution and dynamics of chromatin modification induced by a defined DNA
      double-strand break.
AB  - BACKGROUND: In response to DNA double-strand breaks (DSBs), eukaryotic cells
      rapidly phosphorylate histone H2A isoform H2AX at a C-terminal serine (to form
      gamma-H2AX) and accumulate repair proteins at or near DSBs. To date, these events
      have been defined primarily at the resolution of light microscopes, and the
      relationship between gamma-H2AX formation and repair protein recruitment remains
      to be defined. RESULTS: We report here the first molecular-level characterization
      of regional chromatin changes that accompany a DSB formed by the HO endonuclease
      in Saccharomyces cerevisiae. Break induction provoked rapid gamma-H2AX formation
      and equally rapid recruitment of the Mre11 repair protein. gamma-H2AX formation
      was efficiently promoted by both Tel1p and Mec1p, the yeast ATM and ATR homologs;
      in G1-arrested cells, most gamma-H2AX formation was dependent on Tel1 and Mre11.
      gamma-H2AX formed in a large (ca. 50 kb) region surrounding the DSB. Remarkably,
      very little gamma-H2AX could be detected in chromatin within 1-2 kb of the break.
      In contrast, this region contains almost all the Mre11p and other repair proteins
      that bind as a result of the break. CONCLUSIONS: Both Mec1p and Tel1p can respond
      to a DSB, with distinct roles for these checkpoint kinases at different phases of
      the cell cycle. Part of this response involves histone phosphorylation over large
      chromosomal domains; however, the distinct distributions of gamma-H2AX and repair
      proteins near DSBs indicate that localization of repair proteins to breaks is not
      likely to be the main function of this histone modification.

PMID- 15458643
TI  - The E2-C vihar is required for the correct spatiotemporal proteolysis of cyclin B
      and itself undergoes cyclical degradation.
AB  - BACKGROUND: Proteolytic degradation of mitotic regulatory proteins first requires
      these targets to be ubiquitinated. This is regulated at the level of conjugation
      of ubiquitin to substrates by the anaphase-promoting complex/cyclosome (APC/C)
      ubiquitin-protein ligase. Substrate specificity and temporal activity of the
      APC/C has been thought to lie primarily with its two activators, Cdc20/Fizzy and
      Cdh1/Fizzy-related. RESULTS: Here, we show that reduction in the E2 ubiquitin
      conjugating enzyme (UBC) of the E2-C family that is encoded by the Drosophila
      gene vihar (vih), by either mutation or RNAi, leads to an accumulation of cells
      in a metaphase-like state. Cyclin B accumulates to high levels in all mitotic vih
      cells, particularly at the spindle poles. Vihar E2-C is present in the cytoplasm
      of mitotic cells but also associates with centrosomes, and its own degradation is
      initiated at the metaphase-anaphase transition. Expression of destruction D box
      mutants of vihar in the syncytial embryo results in mitotic arrest at late
      anaphase. In contrast to hypomorphic mutants, Cyclin B is degraded at the spindle
      poles and accumulates in the equatorial region of the spindle. CONCLUSIONS: In
      Drosophila, the Vihar E2 UBC contributes to the spatiotemporal control of Cyclin
      B degradation that first occurs at the spindle poles. APC/C-mediated proteolysis
      of Vihar E2-C autoinactivates the APC/C at the centrosome before a second wave of
      proteolysis to degrade Cyclin B on the rest of the spindle and elsewhere in the
      cell.

PMID- 15458644
TI  - Early- and late-onset blind individuals show supra-normal auditory abilities in
      far-space.
AB  - Blind individuals manifest remarkable abilities in navigating through space
      despite their lack of vision. They have previously been shown to perform normally
      or even supra-normally in tasks involving spatial hearing in near space, a region
      that, however, can be calibrated with sensory-motor feedback. Here we show that
      blind individuals not only properly map auditory space beyond their peri-personal
      environment but also demonstrate supra-normal performance when subtle acoustic
      cues for target location and distance must be used to carry out the task.
      Moreover, it is generally postulated that such abilities rest in part on cross
      modal cortical reorganizations, particularly in the immature brain, where
      important synaptogenesis is still possible. Nonetheless, we show for the first
      time that even late-onset blind subjects develop above-normal spatial abilities,
      suggesting that significant compensation can occur in the adult.

PMID- 15458645
TI  - BYPASS1 negatively regulates a root-derived signal that controls plant
      architecture.
AB  - Plant architecture is regulated by endogenous developmental programs, but it can
      also be strongly influenced by cues derived from the environment. For example,
      rhizosphere conditions such as water and nutrient availability affect shoot and
      root architecture; this implicates the root as a source of signals that can
      override endogenous developmental programs. Cytokinin, abscisic acid, and
      carotenoid derivatives have all been implicated as long-distance signals that can
      be derived from the root. However, little is known about how root-derived
      signaling pathways are regulated. Here, we show that BYPASS1 (BPS1), an
      Arabidopsis gene of unknown function, is required to prevent constitutive
      production of a root-derived graft-transmissible signal that is sufficient to
      inhibit leaf initiation, leaf expansion, and shoot apical meristem activity. We
      show that this root-derived signal is likely to be a novel carotenoid-derived
      molecule that can modulate both root and shoot architecture.

PMID- 15458646
TI  - Tsix transcription- versus RNA-based mechanisms in Xist repression and epigenetic
      choice.
AB  - Recent inquiries have revealed a surprisingly large number (>2500) of naturally
      occurring antisense transcripts, but their function remains largely undiscovered.
      A better understanding of antisense mechanisms is clearly needed because of their
      potentially diverse roles in gene regulation and disease. A well-documented case
      occurs in X inactivation, the mechanism by which X-linked gene expression is
      equalized between XX females and XY males. The antisense gene Tsix determines X
      chromosome choice and represses the noncoding silencer, Xist. In principle, Tsix
      action may involve RNA, the act of transcription, or local chromatin. Here, we
      create novel Tsix alleles to distinguish transcription- versus RNA-based
      mechanisms. When Tsix transcription is terminated before Xist (TsixTRAP), Tsix
      cannot block Xist upregulation, suggesting the importance of overlapping
      antisense transcription. To separate the act of transcription from RNA, we
      knocked in Tsix cDNA in the reverse orientation (Tsix(cDNA)) to restore RNA
      levels in cis without concurrent transcription across Xist. However, Tsix(cDNA)
      cannot complement TsixTRAP. Surprisingly, both mutations disrupt choice,
      indicating that this epigenetic step requires transcription. We conclude that the
      processed antisense RNA does not act alone and that Tsix function specifically
      requires antiparallel transcription through Xist. A mechanism of transcription
      based feedback regulation is proposed.

PMID- 15458647
TI  - SPD-1 is required for the formation of the spindle midzone but is not essential
      for the completion of cytokinesis in C. elegans embryos.
AB  - The process of cytokinesis can be divided into two stages: the assembly and
      constriction of an actomyosin ring giving rise to a narrow intracellular canal
      and the final breaking and resealing of this canal. Mutations in several genes of
      Caenorhabditis elegans disrupt the spindle midzone (anti-parallel microtubules
      and associated proteins that form between the spindle poles) and give rise to
      failures in the completion of cytokinesis. We show that loss of function of spd-1
      causes midzone disruptions, although cytokinesis generally completes. SPD-1 is a
      conserved microtubule-bundling protein that localizes to the midzone and also to
      microtubule bundles in the cytoplasm. The midzone localization of SPD-1 is
      perturbed in embryos depleted of other midzone components, yet the cytoplasmic
      bundles are not affected. We found that two other midzone components also
      localize to the ingressing furrow in wild-type embryos; when SPD-1 is depleted,
      there is no visible midzone, and only this furrow localization remains. SPD-1
      differs from other midzone components in that it is essential for the integrity
      of the midzone, yet not for cytokinesis. Also, it can localize to the midzone
      when other midzone components are depleted, suggesting that SPD-1 may play an
      early role in the pathway of midzone assembly.

PMID- 15458648
TI  - Homeodomain-interacting protein kinase-2 regulates apoptosis in developing
      sensory and sympathetic neurons.
AB  - Excess neurons in the developing nervous system are eliminated by apoptosis, an
      ordered cascade of proteolytic events orchestrated by the caspase family of
      proteases. The apoptotic machinery is tightly regulated by a variety of
      extracellular signals that either activate or suppress apoptosis after binding to
      receptors on neurons. These signals are integrated in neurons by a complex
      network of protein-protein interactions that bring about transcriptional and
      posttranslational changes in key regulators of the apoptotic machinery; such
      regulators include members of the Bcl-2 family. Homeodomain-interacting protein
      kinase-2 (HIPK2) is a recently identified nuclear serine-threonine kinase that
      interacts with homeodomain transcription factors and participates in the
      regulation of cell growth and genotoxic stress-induced apoptosis. Here we show
      that overexpression of HIPK2 in developing neurotrophin-dependent sensory and
      sympathetic neurons promotes apoptosis of these neurons grown with neurotrophins.
      HIPK2-induced apoptosis is caspase-dependent, is inhibited by overexpression of
      Bcl-2 and Bcl-W, and fails to occur in Bax-deficient neurons. Trigeminal sensory
      neurons, which are especially susceptible to HIPK2-induced apoptosis, express the
      highest levels of HIPK2 during the peak of apoptosis in vivo. Knockdown of
      endogenous HIPK2 with antisense oligonucleotides substantially reduces and delays
      apoptosis after neurotrophin deprivation in vitro. These findings identify HIPK2
      as a novel participant in programmed cell death in the developing peripheral
      nervous system.

PMID- 15458649
TI  - Actin filaments align into hollow comets for rapid VASP-mediated propulsion.
AB  - For cells, the growth of a dense array of branched actin filaments organized by
      the actin-related proteins 2 and 3 (Arp2/3) complex at the plasma membrane offers
      an explanation as to how movement is produced, and this arrangement is considered
      to be optimal for motility. Here, we challenged this assumption by using an in
      vitro system of polystyrene beads in cell extracts that contained a complex mix
      of actin polymerization proteins as in vivo. We employed the surface of the bead
      as a reactor where we mixed two different actin polymerization-activating
      factors, the Arp2/3 complex and the vasodilator-stimulated phosphoprotein (VASP),
      to examine their contribution to actin-based movement and filament organization.
      We varied the coating of the bead surface but left the extracts identical for all
      assays. We found that the degree of filament alignment in the actin comet tails
      depended on the surface ratio of VASP to Arp2/3. Alignment of actin filaments
      parallel to the direction of bead movement in the presence of VASP was
      accompanied by an abrupt 7-fold increase in velocity that was independent of bead
      size and by hollowing out of the comets. The actin filament-bundling proteins
      fimbrin and fascin did not appear to play a role in this transformation. Together
      with the idea that VASP enhances filament detachment and with the presence of
      pulling forces at the rear of the bead, a mesoscopic analysis of movement
      provides a possible explanation for our results.

PMID- 15458650
TI  - Blimp-1 specifies neural crest and sensory neuron progenitors in the zebrafish
      embryo.
AB  - Developmental origins of the neural crest (NC), a quintessential and pluripotent
      vertebrate cell type, has historically been a topic of extensive investigation
      but continues to remain poorly understood. In the zebrafish embryo, NC and
      primary sensory neurons are thought to segregate from a common population of
      progenitor cells in response to lateral inhibition. Here, we show that the
      zebrafish homolog of the B-lymphocyte-induced maturation protein (Blimp-1) gene,
      u-boot (ubo), is induced by BMP signaling in cells at the boundary of the neural
      plate and nonneural ectoderm. Loss of Ubo activity not only inhibits
      specification of the NC but also impairs development of the primary sensory
      neurons. Conversely, misexpression of ubo results in the generation of
      supernumerary primary sensory neurons consistent with this cell type representing
      the default fate within the progenitor equivalence group. These results establish
      a link between the activity of the transcriptional regulator Blimp-1 and the
      inductive effects of BMP signaling in the inception of NC progenitor fate.

PMID- 15458651
TI  - Structural biochemistry of ATP-driven dimerization and DNA-stimulated activation
      of SMC ATPases.
AB  - Structural maintenance of chromosome (SMC) proteins play a central role in higher
      order chromosome structure in all kingdoms of life. SMC proteins consist of a
      long coiled-coil domain that joins an ATP binding cassette (ABC) ATPase domain on
      one side and a dimerization domain on the other side. SMC proteins require ATP
      binding or hydrolysis to promote cohesion and condensation, which is suggested to
      proceed via formation of SMC rings or assemblies. To learn more about the role of
      ATP in the architecture of SMC proteins, we report crystal structures of
      nucleotide-free and ATP bound P. furiosus SMC ATPase domains. ATP dimerizes two
      SMC ATPase domains by binding to opposing Walker A and signature motifs,
      indicating that ATP binding can directly assemble SMC proteins. DNA stimulates
      ATP hydrolysis in the engaged SMC ABC domains, suggesting that ATP hydrolysis can
      be allosterically regulated. Structural and mutagenesis data identify an SMC
      protein conserved-arginine finger that is required for DNA stimulation of the
      ATPase activity and directly connects a putative DNA interaction site to ATP. Our
      results suggest that stimulation of the SMC ATPase activity may be a specific
      feature to regulate the ATP-driven assembly and disassembly of SMC proteins.

PMID- 15458652
TI  - The rate of bipolar spindle assembly depends on the microtubule-gliding velocity
      of the mitotic kinesin Eg5.
AB  - During early embryonic cycles, the time required for mitotic spindle assembly
      must match the autonomous cell cycle oscillations because a lack of coordination
      between these two processes will result in chromosome segregation errors. Members
      of the widely conserved BimC kinesin family are essential for spindle formation
      in all eukaryotes, and complete loss of BimC function results in monopolar
      spindles that have two spindle poles that are not separated. However, the precise
      roles of BimC motor activity in the spindle assembly process are not known. To
      examine the contribution of BimC kinesin's motor activity to spindle assembly, we
      generated and characterized mutants of Eg5, a vertebrate BimC kinesin, with
      reduced in vitro microtubule-gliding velocities. In Xenopus egg extracts, we
      replaced endogenous Eg5 with recombinant wild-type or mutant motor proteins. By
      using centrosome-dependent and centrosome-independent spindle assembly assays, we
      found that mechanisms that determine spindle size and shape were robust to
      approximately 6-fold reductions in Eg5 motility. However, the spindle assembly
      process was slower when Eg5 motor function was impaired. This role of Eg5 was
      independent of its contribution to centrosome separation. We provide evidence
      that Eg5 is a rate-limiting component of the cellular machinery that drives
      spindle assembly in vertebrates.

PMID- 15458653
TI  - Fears grow about animal rights activists.
AB  - The British government has blocked entry to a key American animal rights
      campaigner but there are growing concerns about local developments.

PMID- 15458654
TI  - An Austrian foothold in the tropics.
AB  - Researchers from a small European country have backed a project set up ten years
      ago in Costa Rica that has now become a major influence in conservation and
      research.

PMID- 15458656
TI  - Jerry Coyne.

PMID- 15458657
TI  - Gorillas.

PMID- 15458658
TI  - The visual perception of motion.

PMID- 15458659
TI  - Dual capacity of a human olfactory receptor.

PMID- 15458660
TI  - Adherin: key to the cohesin ring and cornelia de Lange syndrome.
AB  - Adherin facilitates sister chromatid cohesion, DNA repair and binding of the
      cohesin complex to chromosomes. New studies indicate that adherin activity is
      coordinated with DNA replication and chromosome segregation, and that its dosage
      is critical for gene expression and human development.

PMID- 15458661
TI  - Neuronal microcircuits: frequency-dependent flow of inhibition.
AB  - New work suggests that feedback inhibition of neurons in the hippocampus is
      mediated by two distinct microcircuits. Interneurons targeting a neuron's soma
      are triggered by onset of activity, while those targeting distal dendrites are
      recruited by sustained activity. These circuits may thus convey information about
      the timing and rate of activity, respectively.

PMID- 15458662
TI  - Floral development: an ABC gene chips in downstream.
AB  - In flower development, specification of stamens and carpels requires the AGAMOUS
      gene. A recent study has now shown that AGAMOUS also plays more specific roles in
      the regional activation of sporocyte formation.

PMID- 15458663
TI  - Sea turtles: old viruses and new tricks.
AB  - Recent years have seen an inexplicable increase in the frequency of an appalling
      disease in sea turtles: fibropapillomatosis, which is likely caused by a
      herpesvirus and causes tumors to grow throughout the turtle's body. New research
      has led to the disturbing conclusion that recent, human-induced environmental
      changes are responsible.

PMID- 15458664
TI  - Ciliogenesis: polarity proteins on the move.
AB  - The formation and maintenance of cilia and flagella require a selective and
      directed transport along the axoneme, a characteristic central bundle of
      microtubules. Recent evidence suggests an interesting link between the generation
      of cilia and the protein complexes that establish apico-basal cell polarity.

PMID- 15458665
TI  - Cryptochromes: tail-ored for distinct functions.
AB  - Cryptochromes are important components of circadian clocks in both plants and
      animals. Recent work suggests that the carboxy-terminal tails of these conserved
      proteins are used in drastically different ways in different organisms.

PMID- 15458666
TI  - Visual attention: bottom-up versus top-down.
AB  - Visual attention is attracted by salient stimuli that 'pop out' from their
      surroundings. Attention can also be voluntarily directed to objects of current
      importance to the observer. What happens in the brain when these two processes
      interact?

PMID- 15458667
TI  - Synapse scaffolding: intersection of endocytosis and growth.
AB  - The Drosophila dynamin-associated protein Dap160, homolog of the vertebrate
      Intersectins, is thought likely to act as a molecular scaffold in the synaptic
      periactive zone. New mutant analyses have revealed separable roles for Dap160 in
      the regulation of vesicular endocytosis and synaptic growth.

PMID- 15458668
TI  - Evasive maneuvers by secreted bacterial proteins to avoid innate immune
      responses.
AB  - To cause disease, bacterial pathogens must first breach physical barriers, such
      as the mucous membrane that lines organs, and then successfully replicate and
      disseminate while avoiding destruction by the immune system. Many bacterial
      pathogens accomplish this by secreting proteins into their host environment,
      which act to subvert or dampen the expanding immune response. Here, we discuss
      how bacterial pathogens use an arsenal of secreted virulence proteins to modify
      the outcome of innate immune activation by altering how the immune system
      recognizes microbial invaders.

PMID- 15458669
TI  - Integrated reconstructive strategies for treating the anophthalmic orbit.
AB  - INTRODUCTION: Anophthalmia may be congenital or acquired. Congenital anophthalmia
      refers to any orbit that contains a severely hypoplastic eye at birth
      (microphthalmia), or a complete absence of the globe due to failure of optic
      vesicle formation. In both those cases the aim of surgery is to stimulate
      adequate orbital growth. Acquired anophthalmic orbit may be due to trauma or
      tumour. In acquired forms the goal is restoration of orbital volume with adequate
      replacement of orbital contents. PATIENTS AND METHODS: In this study 28 patients
      (6 cases of congenital and 22 of acquired anophthalmia), were treated between
      October 1997 and August 2002, by applying protocols that are based on data from
      the literature. RESULTS: In 19 cases there were satisfactory results.
      Complications such as implant dislocation (3 cases), residual asymmetry (2
      cases), and eyelid retraction required revisional surgery (4 cases). CONCLUSIONS:
      The different strategies applied for reconstructing the missing structures of the
      orbit in the congenital forms have given satisfactory results related to the type
      and complexity of the deformity. In rehabilitating a patient with an acquired
      anophthalmic orbit it is essential to ensure that the patient has realistic
      expectations regarding a final prosthesis. Interaction of the various healthcare
      professionals is also essential to help the patient and so develop new prosthetic
      devices as well as innovative methods for socket reconstruction.

PMID- 15458670
TI  - Fronto-orbital advancement with simultaneous LeFort III-distraction.
AB  - BACKGROUND: Patients with pronounced forms of craniosynostosis often suffer from
      hypoplasia of the facial skeleton. Different techniques have been described to
      correct these malformations consisting mainly of a standardised fronto-orbital
      advancement to correct the neurocranium followed by a conventional LeFort III
      osteotomy for the correction of the viscerocranium several months later. METHOD
      AND PATIENTS: In order to optimise treatment, these techniques were confined into
      a one step procedure. This comprised a standard fronto-orbital advancement and a
      simultaneous LeFort III-osteotomy, followed by distraction of the facial skeleton
      7 days later using a rigid external distractor (RED). RESULTS: Six patients have
      been treated with excellent functional and cosmetic results and a high rate of
      patients' satisfaction. Postoperatively, one patient suffered from rhinorrhoea
      necessitating revision of the base of the skull 7 days later. In a second
      patient, the RED distractor could not be fixed due to insufficient ossification
      of the skull 6 months after subtotal craniectomy. In another patient, partial
      necrosis of the calvarial skin occurred. No other significant adverse events
      occurred. DISCUSSION: Upto today the LeFort III advancement plus fronto-orbital
      advancement were always performed intraoperatively in one single step. When
      applying the distraction technique, the viscerocranium can be transposed much
      further than by conventional techniques. Beside this, using the external RED
      distractor, the distraction vector can be modified and adjusted according to
      clinical progress postoperatively. In addition, the time gap between the
      operation and start of distraction allows the soft tissues to reattach, probably
      reducing the risk of ascending infections. CONCLUSION: The combination of fronto
      orbital advancement and LeFort III advancement by distraction can optimise the
      clinical outcome and lower the risk of ascending infections.

PMID- 15458671
TI  - Regeneration of mandibular condyle following unilateral condylectomy in canines.
AB  - PURPOSE: The purpose of this experimental study was to investigate regeneration
      of the mandibular condyle after unilateral condylectomy in canines. MATERIAL AND
      METHODS: Five 2-year-old beagle dogs underwent unilateral mandibular condylectomy
      and were sacrificed either immediately postoperatively (n=1) or 3 months later
      (n=4). Temporomandibular joints were examined radiologically and histologically,
      and sides were compared. RESULTS: All joints showed postoperative regeneration of
      the condylar head. Maximum regeneration of the condyle occurred medially, where
      most bone of the glenoid fossa was present, rather than laterally. From an
      anteroposterior perspective, regeneration of the condylar head was more
      favourable anteriorly, facing the inferior slope of the glenoid fossa.
      Regenerated articular cartilage was irregular. Articular discs displayed central
      thickening compared with unoperated joints. The bone of the glenoid fossa was
      normal. CONCLUSION: Unilateral mandibular condylectomy in canines resulted in a
      certain degree of condylar regeneration during a 3-month postoperative period,
      with some irregular articular cartilage formation.

PMID- 15458672
TI  - A three-dimensional computer model of the human mandible in two simulated
      standard trauma situations.
AB  - PURPOSE: A three-dimensional finite element model of the human mandible was
      developed to simulate and analyse biomechanical behaviour in two standard trauma
      situations. This computer-based study was made to assess the stress patterns
      within human mandibles generated by impact forces. MATERIAL AND METHODS: The
      mandibular model was generated using 7.073 nodes and 30.119 tetrahedra. A
      commercial finite element solver was then applied to this mesh to compute
      stresses generated in standard trauma situations (a blow in the symphysis region
      and another one to the body of the mandible). RESULTS: The results indicate that
      following a blow to the symphysis region, maximum stress areas were located at
      the symphysis, retromolar and condylar regions. In the case of a blow to the
      mandibular body, the maximum stress areas were located at the contralateral
      angle, the ipsilateral body and the ipsilateral condylar neck regions.
      CONCLUSION: The main application of this study was the prediction of fractures as
      a consequence of known forces.

PMID- 15458673
TI  - Maxillofacial fractures. Analysis of demographic distribution and treatment in
      2901 patients (25-year experience).
AB  - INTRODUCTION: The aim of this study was to analyse retrospectively the
      demographic distribution, treatment modalities, and complications of
      maxillofacial fractures in 2901 patients treated in this department in Southeast
      Anatolia between 1978 and 2002. In addition, the use of internal fixation was
      evaluated in an effort to determine whether there were changes in using internal
      fixation techniques. PATIENTS AND METHODS: Two thousand nine hundred and one
      cases of facial trauma were assessed according to age, sex, and aetiology, in
      addition to the distribution of the fractures relating to facial bones and
      seasons. RESULTS: It was found that facial fractures were most frequent in males
      (77.5%) and in the 0-10 year age group; they tended to be more frequent during
      summer (36.3%); and traffic accidents were the most common aetiological factor
      (38%). 77.9% of cases were treated with conservative methods, and 22.1% with one
      or more internal fixation techniques. The most favoured technique was miniplate
      osteosynthesis; the complication rate associated with internal fixation was 5.7%.
      CONCLUSION: Currently there are many techniques to be used in treating
      maxillofacial trauma. However, the experience of the surgical team is also an
      important factor in achieving satisfactory functional and aesthetic results, and
      in minimizing complications.

PMID- 15458674
TI  - The frontal sinus: a culprit or a victim? A review of 40 cases.
AB  - PURPOSE: Frontal sinus fractures represent 2-12% of facial trauma. The purpose of
      this article is to discuss proper management of these fractures and to evaluate
      the indications for treatment, the complications and the morphologic results of
      surgery. MATERIAL AND METHODS: The records of 40 patients admitted to this
      department with a frontal sinus fracture were reviewed. Sex, age, the
      circumstances of injury, the imaging techniques, fracture patterns, associated
      injuries, length of hospital stay, surgical approaches and the complications were
      analysed. The operations included 3 main options: cranialization, obliteration or
      reconstruction of the frontal sinus. RESULTS: There were 32 men and 8 women
      (average 34 years). The most common cause of injury was motor vehicle accidents.
      Conventional radiography of the face was complemented by computed tomography and
      3D reconstructions. Isolated anterior table fractures were found in 72.5% and
      combined anterior/posterior table fractures in 27.5% of the cases. The treatment
      was surgical for 70% of the patients; the average length of hospitalization was 1
      week. Postoperative complications were: 1 brain abscess, 2 cases of frontal
      sinusitis and 2 cases of chronic headache. CONCLUSION: Long-term complications in
      frontal sinus fractures are intracranial infection, sinusitis and forehead
      defects. To avoid these it was decided to treat all displaced fractures
      surgically in displaced anterior table fractures the sinus was obliterated with
      cancellous bone and in displaced posterior table fractures the sinus was
      cranialized.

PMID- 15458675
TI  - Influence of marginal and segmental mandibular resection on the survival rate in
      patients with squamous cell carcinoma of the inferior parts of the oral cavity.
AB  - AIM: The aim of this retrospective study was to investigate whether radical
      (segmental resection) or conservative (marginal) resection of mandibular bone
      influenced patients, survival. PATIENTS AND METHODS: A series of 136 patients
      selected for partial mandibular resection for the treatment of squamous cell
      carcinomas of the lower oral cavity was evaluated retrospectively. Fifty-four
      patients underwent marginal and 82 cases segmental resection of the mandible. The
      mean follow-up periods were 91.1+/-30.1 months and 91.5+/-26.2 months,
      respectively. Data was extracted from the patient records and transferred into a
      database for statistical evaluation. Results Mean survival was 63.0+/-35.3 months
      for marginal and 53.1+/-32.3 months for segmental resection. The overall survival
      rate was analysed according to Kaplan-Meier and the test of significance (Log
      Rank) which yielded no statistically significant difference in the survival rate
      between both groups (p=0.1119). Numbers of recurrences, second primaries,
      metastases and/or postoperative complications were similar in both groups, i.e.
      no statistically significant differences were observed (ANOVA, Post-hoc Scheffe
      test). Conclusion In cases with an indication for bone resection, marginal
      resection may achieve satisfactory control and is as effective as segmental
      resection.

PMID- 15458676
TI  - Sigmoid and transverse sinus thrombosis caused by mastoid implant -- case report.
AB  - INTRODUCTION: Extraoral craniofacial implants are often used for retention of
      auricular prostheses. In this case report, the rare complication of sigmoid and
      transverse sinus thrombosis after implant placement in the mastoid is described.
      CASE REPORT: A 36-year-old man with congenital hypoplasia of the right ear was
      treated with an implant-based auricular prosthesis. One of the three implants in
      the mastoid area had to be removed because of an infection, whereas the other two
      implants were removed at the patient's request. Twenty-four days after implant
      removal, he was seen with sigmoid and transverse sinus thrombosis and
      successfully treated with fibrinolytic and consecutive anticoagulation therapy.
      CONCLUSIONS: Implants in the mastoid area are a very important aid for retention
      of auricular prostheses, but may have life-threatening intracranial consequences.

PMID- 15458677
TI  - Colon perforation with acute peritonitis after taking clindamycin and diclofenac
      following wisdom tooth removal.
AB  - INTRODUCTION: Non-steroidal anti-inflammatory drugs have a high analgesic and
      anti-inflammatory effect and are widely taken for acute and chronic pain.
      Especially following long-term use, they may cause gastrointestinal side effects
      such as mucosal ulceration, perforation and strictures in the small and large
      bowel. PATIENT: A 16-year-old female developed colonic perforation and purulent
      peritonitis after wisdom tooth removal and short-term intake of non-steroidal
      anti-inflammatory drugs. DISCUSSION: Non-steroidal anti-inflammatory drugs may
      exert their deleterious effects on the lower gastrointestinal tract through both
      local and systemic actions. Systemic effects are caused by the inhibition of
      cyclooxygenase and reduction of protective prostaglandins. The local damage of
      the intestinal mucosa in the distal bowel segments seems to be caused by
      sustained release formulation with a high enterohepatic circulation. The latter
      may act time and again on the intestinal mucosa through metabolites secreted in
      the gallbladder. Concomitant intake of clindamycin may have favoured this acute
      complication. CONCLUSION: Intestinal perforation after short-term intake of non
      steroidal anti-inflammatory drugs is very rare. However, it is life-threatening
      and illustrates the need for careful prescribing at as low an effective dose and
      as short a time as possible, especially when combining different drugs.
      Paracetamol only has a weak effect on cyclooxygenase and continues to be a
      possible alternative for postoperative dental pain with a favourable benefit-risk
      ratio. It is the drug of choice for children, adolescents and patients with an
      increased risk of non-steroidal anti-inflammatory drug-induced gastro
      enteropathy.

PMID- 15458678
TI  - Mucoceles as a complication of submandibular intubation.

PMID- 15458679
TI  - Macrovascular complications of metabolic syndrome: an early intervention is
      imperative.
AB  - The metabolic syndrome is a widespread clinical condition and an important
      cluster of atherothrombotic disease risk factors. The inclusion of this syndrome
      in the recently published Adult Treatment Panel III (ATP III) guidelines focused
      the attention of the physicians on this entity. Abdominal obesity, PPAR
      modulation, insulin resistance (with or without glucose intolerance), atherogenic
      dyslipidemia, elevated blood pressure, prothrombotic and proinflammatory states
      are the principal factors of this multifaceted syndrome. There are two major
      pathways of metabolic syndrome progress: (1) With preserved pancreatic beta cells
      function and insulin hypersecretion, which can recompense for insulin resistance.
      This pathway leads mostly to the macrovascular complications of metabolic
      syndrome. (2) With substantial injure of pancreatic beta cells leading to
      gradually reduced insulin secretion and to hyperglycemia (e.g. overt type 2
      diabetes). This pathway leads to both microvascular and macrovascular
      complications. Because macrovascular complications of insulin resistance state
      precede the onset of hyperglycemia, early intervention in patients with metabolic
      syndrome is particularly important. Since central obesity (accompanied by insulin
      resistance even in the absence of hyperglycemia) is the key factor leading to
      development of metabolic syndrome and its future macrovascular complications, we
      assume that next logical step is the recognition of central obesity itself as a
      major risk factor for cardiovascular diseases.

PMID- 15458680
TI  - Sarcoid heart disease: clinical course and treatment.
AB  - Sarcoidosis is a rare granulomatous disease of unknown etiology that can affect
      any organ. Cardiac involvement, although uncommon, has a wide spectrum of
      clinical manifestations and is potentially fatal. Although there is no agreement
      upon a strategy for the diagnosis (which is difficult to make based on clinical
      information alone), the introduction of newer technology is promising and may be
      useful both for the early diagnosis of cardiac involvement and for the evaluation
      of response to therapy. Early treatment is crucial in improving symptoms and
      prognosis. ICD implantation and cardiac transplantation may offer improvements in
      management, as steroid therapy and pacemaker implantation has led to improved
      outcomes over the past three decades.

PMID- 15458681
TI  - Third heart sound: genesis and clinical importance.
AB  - Auscultation of third heart sound has been performed for more than a century, an
      interest that not only persists today, but also has experienced renewed emphasis.
      Sophisticated study of the third heart sound by current investigative techniques
      has underscored the value of clinical detection with the time-honored
      stethoscope. This review re-examines the mechanisms of genesis of third heart
      sound in regard to the hemodynamic and echocardiographic aspects, and its
      clinical importance.

PMID- 15458682
TI  - The effect of pulmonary hypertension on left atrial mechanical functions in
      chronic obstructive lung disease.
AB  - BACKGROUND: Left atrial (LA) function is an important determinant of left
      ventricular (LV) filling. However, the effect of pulmonary hypertension (PH) on
      LA mechanical function in chronic obstructive lung disease (COLD) has not been
      studied, yet. METHODS: 49 patients with COLD and 25 controls were included in
      this study. Patients were divided into two subgroups: patients without PH (group
      1, n=21) and with PH (group 2, n=28). LA volumes were determined at mitral valve
      opening (Vmax), at onset of atrial systole (Vp) and at mitral valve closure
      (Vmin) according to biplane area-length method. The following LA parameters were
      calculated: passive emptying volume (PEV=Vmax-Vp), conduit volume [CV=LV stroke
      volume-(Vmax-Vmin)], passive emptying fraction (PEF=PEV/Vmax), active emptying
      volume (AEV=Vp-Vmin), active emptying fraction (AEF=AEV/Vp), total emptying
      volume (TEV=Vmax-Vmin), percent contribution of PEV, CV and AEV to LV stroke
      volume. RESULTS: Vmax (p<0.01), PEV (p<0.001) and TEV (p<0.05) were lower in
      group 2 than in the controls, and the differences between group 1 and control
      group were insignificant (p>0.05). Vp, Vmin, CV and AEV did not differ among
      three groups. Percent contribution to LV filling of the PEV was decreased in
      group 2 when compared to group 1 (p<0.05) and the controls (p<0.01). Percent
      contribution to LV filling of the AEV was increased in group 2 when compared to
      the controls (p<0.05). There were inverse correlations between pulmonary artery
      pressure and the following parameters: LV stroke volume (r=-0.43, p<0.01), mitral
      E/A (r=-54, p<0.001), Vmax (r=-0.35, p<0.05), PEV (r=-40, p<0.01) and PEF (r=
      0.43, p<0.01). CONCLUSION: This study shows that the alterations of LA mechanical
      functions in patients with COLD are closely correlated to PH levels. Furthermore,
      these results underline the importance of maintaining a sinus rhythm in these
      patients.

PMID- 15458683
TI  - Predictors and prognostic value of myocardial injury following stent
      implantation.
AB  - BACKGROUND: Troponin I concentrations are frequently elevated following
      percutaneous coronary intervention (PCI) even in procedures without complications
      and are considered, by some, as predictive of long-term morbidity and mortality.
      We assessed whether post-PCI troponin I concentrations bore any relationship to
      clinical, angiographic and in-laboratory minor adverse events indicative of
      myocardial injury and evaluated, in follow-up, whether these levels are useful as
      a predictive markers of adverse events. METHODS: Patients (n=147) who were
      scheduled for PCI for stent placement were prospectively studied. In-laboratory
      events recorded were protracted chest pain, electrocardiographic changes, slow
      flows, dissections and lateral branch affectation. Troponin I and creatinine
      kinase MB fraction (CK-MB) mass were measured at baseline and post-procedure.
      Mean clinical follow-up was for 10.4+/-3.6 months. RESULTS: During PCI, at least
      one adverse event occurred in 34% of patients and, in 38% of them, there was an
      elevation of troponin I as compared to 5.1% of those patients without any adverse
      event (relative risk=7.4; P<0.001). Elevation of troponin I concentrations
      occurred in 16.3% of all patients, 79.2% associated with an AE. CK-MB was
      elevated in 15.6% of patients. On multivariate analysis, protracted chest pain,
      lateral branch involvement and slow flow remained statistically significant in
      relation to post-procedure elevations of troponin I concentrations. Clinical
      follow-up showed a poorer prognosis in patients who had had elevated troponin I
      concentrations. CONCLUSIONS: In-laboratory adverse event predict elevated post
      procedure troponin I concentrations which are associated with myocardial injury.
      These elevations, in turn, predict poorer medium-term clinical outcomes.

PMID- 15458684
TI  - Smoking increases the risk of coronary artery disease in Chinese with Chlamydia
      pneumoniae infection.
AB  - BACKGROUND: The infection with Chlamydia pneumoniae (Cp) has been claimed to
      associate with coronary artery disease (CAD). However, the seroepidemiological
      study of association between Cp infection and CAD still remains a source of
      controversy. The aim of the present study is to investigate the possible
      association of Cp infection with CAD in Chinese mainland population and the
      potential role of Cp infection combined with the traditional risk factors in CAD.
      METHODS: 1422 hospitalized patients with angiographically demonstrated CAD and
      297 controls were recruited and tested for specific Cp IgG with enzyme-linked
      immunoassay (ELISA). RESULTS: The prevalence of Cp IgG seropositivity in patients
      with CAD was significantly higher than that in controls (31.1% vs. 24.9%,
      P=0.035). Unadjusted odds ratios (OR) and 95% confidence intervals (CI) for CAD
      with the presence of seropositivity of IgG to Cp was 1.4 (1.0-1.8). After full
      adjustment for possible confounders on multiple logistic regression analysis,
      only a weak association of Cp infection with CAD was found. The adjusted OR (95%
      CI) for CAD associated with Cp infection was 1.3 (0.95-1.71, P=0.1). To further
      delineate the potential role of Cp infection in CAD, we divided subjects into
      seropositive (n=516) and seronegative (n=1203) groups according to their Cp IgG
      status. Notably, the adjusted OR (95% CI) for CAD associated with smoking was 4.0
      (1.8-8.6) in the seropositive group, 0.9 (0.5-1.4) in the seronegative group,
      indicating that smoking can significantly increase the risk of CAD in subjects
      with Cp infection. CONCLUSIONS: Cp infection is not strongly associated with CAD
      in Chinese mainland population; however, smoking increases the risk of CAD in
      those with Cp infection.

PMID- 15458685
TI  - No association of interleukin-6 gene polymorphism (-174 G/C) with myocardial
      infarction or traditional cardiovascular risk factors.
AB  - BACKGROUND: Recently, a polymorphism at position -174 (G>C) of the interleukin-6
      (IL-6) promoter was found to be associated with an increased prevalence of
      myocardial infarction (MI). The aim of the present study was to further
      investigate the association of the IL-6 -174 G/C allele status with specific end
      organ damage, i.e. myocardial infarction in large population-based samples.
      METHODS: Individuals from two Bavarian samples of MI patients (total n=1322) and
      the population-based Augsburg MONICA survey (1023 unselected controls) were
      studied by questionnaire, physical examination, echocardiographical assessment
      and biochemical analyses. The -174 G/C polymorphism was genotyped using a newly
      established PCR-RFLP. IL-6 levels were measured in a subset of 574 MI patients.
      RESULTS: In the population-based sample, the IL-6 genotype was neither associated
      with traditional cardiovascular risk factors (systolic and diastolic blood
      pressure, total cholesterol, HDL and LDL cholesterol, body mass index, diabetes
      mellitus) nor with cardiac structural or functional parameters (left ventricular
      mass index, ejection fraction, diastolic inflow pattern). Moreover, the genotype
      distribution of the -174 G/C polymorphism was not different in MI patients (GG:
      34.1%; GC: 47.4%; CC: 18.5%) and population-based controls (GG: 32.4%; GC: 48.8%;
      CC: 18.9%) (p=0.67). IL-6 levels were neither related to the -174 G/C
      polymorphism (p=0.29) nor to ACE-inhibitor treatment (2.16 with vs. 2.09 pg/ml
      without ACE-inhibitor, p=0.27). However, patients receiving statins displayed
      significantly lower IL-6 levels (1.83 vs. 2.32 pg/ml in the group without
      statins, p<0.0001). CONCLUSIONS: This extensive investigation failed to obtain
      evidence that the IL-6 -174 G/C promoter polymorphism affects traditional
      cardiovascular risk factors or the prevalence of myocardial infarction in a
      Caucasian sample.

PMID- 15458686
TI  - Functional and morphological cardiac changes in myeloproliferative disorders
      (clinical study).
AB  - PURPOSE: Cardiac involvement is not well defined in myeloproliferative disorders
      (MPD). The purpose of this study was to evaluate the cardiac involvement by
      transthoracic echocardiography in MPD. MATERIALS AND METHODS: The study groups
      were 36 patients (mean age: 58+/-15 years, 20 female and 16 male) with MPD and 30
      age-matched healthy controls. MPD group included 15 essential thrombocythemia
      (ET), eight chronic phase chronic myelogenous leukemia (CML), seven idiopathic
      myelofibrosis (MF) and six polcythemia vera patients. RESULTS: Valvular
      regurgitations were present in 14 patients (39%) and eight controls (27%),
      (P>0.05). Mitral regurgitation (MR) was more prominent in CML compared to
      controls (P=0.044). The rates of annular calcifications, valvular thickening, and
      vegetation like lesions were not different between MPD and control groups.
      Pulmonary hypertension (PHT) was present in six (17%) patients, but none of the
      controls (P=0.021). The rates of PHT in CML and MF were significantly higher than
      controls (P<0.05). The rate of PHT was not different in-between MPD patients with
      and without thromboembolic events, however, in MPD cases with thromboembolic
      events PHT was more common compared to controls (P=0.037). CONCLUSION: This study
      showed that valvular lesions were not more prevalent in MPD. PHT was the most
      prominent cardiac pathology in MPD (especially in CML, MF and thromboembolic
      events subgroups) compared to controls. Further evaluation of the cardiac changes
      in MPD subgroups with extended studies including trans-oesophageal
      echocardiography and longer follow-up periods would be appropriate.

PMID- 15458687
TI  - Cardiovascular outcome in hospitalized patients with minimal troponin I elevation
      and normal creatine phosphokinase.
AB  - BACKGROUND: Among patients with acute coronary syndrome, elevated cardiac
      troponin and creatine phosphokinase MB fraction levels have both prognostic and
      diagnostic values. However, in hospitalized patients, cardiac biomarkers are
      measured in a variety of clinical situations including but not limited to acute
      coronary syndrome. Moreover, these patients may have elevated troponin levels
      with no increase in creatine phosphokinase MB fraction levels. OBJECTIVE: To
      evaluate the cardiovascular outcome of acutely ill, hospitalized patients with
      minimal troponin I increase with normal creatine phosphokinase MB fraction.
      METHODS: We identified 64 patients retrospectively from our database with minimal
      troponin I increase and normal creatine phosphokinase MB fraction hospitalized
      between November 1998 and April 2000. Discharged patients were questioned about
      re-hospitalization for myocardial infarction, unstable coronary syndrome,
      congestive heart failure and percutaneous coronary intervention by means of a
      structured questionnaire. For those patients who died during hospitalization,
      data were collected from hospital records. For patients who died at home or at a
      different institution, a surviving relative completed the questionnaire. Primary
      outcomes were death, myocardial infarction and the need for revascularization or
      re-hospitalization. RESULTS: Composite endpoint of death, myocardial infarction,
      percutaneous coronary intervention or coronary artery bypass grafting and re
      hospitalization for cardiac cause occurred in 35.95% of patients within 1 year.
      CONCLUSIONS: There is a significant composite event rate of death, myocardial
      infarction or re-hospitalization for cardiac causes in acutely ill, hospitalized
      patients with normal creatine phosphokinase MB fraction and minimally elevated
      troponin I, regardless of the cause for hospitalization.

PMID- 15458688
TI  - Effects of cocaine and caffeine alone and in combination on cardiovascular
      performance: an experimental hemodynamic and coronary flow reserve study in a
      canine model.
AB  - BACKGROUND: With the proliferation of cocaine abuse, increased incidence of
      catastrophic cardiovascular events like angina pectoris, myocardial infarction,
      ventricular arrhythmias or sudden death are reported. Cocaine-dependent subjects
      commonly abuse multiple substances. Many of them drink coffee before and after
      cocaine use. The high frequency of simultaneous exposure to both the drugs may
      influence outcome of the cocaine's treatment. Cocaine and caffeine's independent
      effects on cardiodynamics are documented but to our knowledge combined effects of
      both on complete cardiovascular hemodynamics remains to be examined. METHODS:
      Eighteen dogs were instrumented to pass cardiac catheters into right and left
      heart. The experiments were performed after they recovered from the effects of
      anesthesia. In phase I (30 experiments on 8 dogs), the doses were established by
      dose-response curve. In phases II and III, another 10 dogs were subjected to 28
      experiments. They were given i.v. cocaine followed by caffeine and vice versa to
      study their effects on hemodynamics and coronary flow reserve. RESULTS: Phase 1:
      The doses of cocaine (2 mg/kg) and caffeine (5 mg/kg) were established. Phase II:
      Cocaine increased heart rate, blood pressure and dP/dt but CFR decreased
      significantly. Caffeine administered after cocaine attenuated these effects
      (dP/dt decreased to 4910+/-104 from 5066+/-110 mm Hg s; p<NS). Phase III:
      Caffeine mildly increased hemodynamic parameters but reduced dP/dt. Cocaine's
      administration as the second drug had synergistic excitatory effects (dP/dt
      increased to 6166+/-160 from 5055+/-142 mm Hg/s; p<0.04). CFR decreased
      significantly. CONCLUSION: Cocaine increased heart rate, blood pressure and dP/dt
      but reduced CFR. Caffeine mildly increased the hemodynamic variables but
      decreased CFR. Combined cocaine+caffeine attenuated the excitatory effects of
      cocaine significantly. A reversed drug combination i.e., caffeine+cocaine
      generated synergistic excitatory effects on the cardiovascular system of the
      dogs. CFR showed significant decrease.

PMID- 15458689
TI  - Clinical features of isolated left ventricular noncompaction in children.
AB  - BACKGROUND: Ventricular noncompaction is a rare unclassified cardiomyopathy due
      to intrauterin arrest of compaction of the loose interwoven meshwork with limited
      data regarding diagnosis and outcome in children. METHODS: In this study we
      describe clinical features of isolated left ventricular noncompaction (IVNC) in
      children and compare our findings with those previously reported. A diagnosis of
      ventricular noncompaction was made according to the characteristic
      echocardiographic appearance of two-layered myocardial wall consisting of a thin
      compacted epicardial and a thick noncompacted endocardial layer with numerous,
      prominent trabeculations and deep intertrabecular recesses communicating with
      left ventricular cavity. RESULTS: Nine children, eight male and one female, with
      ages ranging from 10 days to 12 years and follow-up as long as 5 years were
      included into the study. The primary diagnosis of IVNC had been missed in four of
      the patients. Clinical manifestations were heart failure in five patients,
      cardiac murmur in two, dizziness in one, and palpitation in one patient. All
      patients, except two asymptomatic ones, had electrocardiographic abnormalities.
      Four patients required hospital admission for decompansated heart failure. Two
      patients died during follow-up while waiting for heart transplantation. Familial
      occurrence, ventricular tachycardia and thromboembolic events were not observed
      in any of the patients. CONCLUSIONS: Although IVNC is present at birth, it may
      become clinically overt at any time from infancy through adolescence. Physicians
      and echocardiographers should be familiar with the diagnostic pattern of
      ventricular noncompaction in order to prevent any delay in diagnosis. Since
      associated morbidity and mortality rates are high, these patients require regular
      follow-up.

PMID- 15458690
TI  - Comparative effects of statin and fibrate on nitric oxide bioactivity and matrix
      metalloproteinase in hyperlipidemia.
AB  - OBJECTIVE: Because the lipoprotein effects of statin and fibric acid derivatives
      therapies differ, we studied the effects of these therapies in patients with
      hyperlipidemia on lipoproteins, vasomotor function, and plaque stability.
      METHODS: We administered simvastatin, 20 mg daily, to 27 patients with
      hypercholesterolemia and coronary artery disease, or fenofibrate, 200 mg daily,
      to 27 patients with pure hypertriglyceridemia during 8 weeks. RESULTS: As
      expected, simvastatin significantly lowered total cholesterol and low-density
      lipoprotein cholesterol (LDL-C) more, and fenofibrate decreased triglyceride and
      increased high-density lipoprotein cholesterol (HDL-C) more than either therapy.
      Simvastatin and fenofibrate significantly improved the percent flow-mediated
      dilator response to hyperemia by 183+/-41% and by 30+/-7%, respectively (each
      P<0.001); however, simvastatin significantly improved more (P<0.001). Simvastatin
      and fenofibrate significantly lowered plasma levels of tumor necrosis factor
      alpha (TNF-alpha) by 13+/-4% and by 10+/-4%, respectively (P=0.009 and P=0.006,
      respectively) with a similar degree (P=0.614). Simvastatin significantly reduced
      plasma levels of total MMP-9 and TIMP-1 more (P=0.005 and P=0.036, respectively),
      compared with fenofibrate showing no reduction. There were significant
      correlations between the degree of changes in TNF-alpha and the degree of changes
      in MMP-9 activity (r=0.376, P=0.053). CONCLUSIONS: Simvastatin and fenofibrate
      demonstrated antiatherosclerotic effects via different mechanisms.

PMID- 15458691
TI  - Cardio: a web-based knowledge resource of genes and proteins related to
      cardiovascular disease.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading killer for human. In
      order to understand the linkage between cardiovascular diseases and genes or
      proteins, it is essential to construct a database to organize the body of
      knowledge. While the existing molecular biological databases focus on the
      sequence and structural aspects of biological macromolecules, i.e. DNAs, RNAs and
      proteins, Cardio is the web-based system we built to provide a knowledge
      environment with visual interface to integrate information about major
      cardiovascular diseases in relation to genes and proteins. METHODS: We collected
      the information from the web by using a group of software we developed and used a
      relational database management system to manage the information of these data.
      RESULTS: Cardio consists of six sections: GENE, PROTEIN, DISEASE, DRUG, LINKS,
      and REFERENCE. Each section contains relevant information about the topic. Using
      a phenotype-driven approach, we can identify genetic mechanisms underlying the
      physiology and pathophysiology of specific cardiovascular disease, such as
      atherosclerosis, hypertension, heart failure, and stroke. CONCLUSION: The website
      titled "Database of Genes and Proteins Related to Cardiovascular Disease
      (Cardio)" is available at along with additional information on cardiovascular
      disease, supplementary materials and related figures.

PMID- 15458692
TI  - Plasma B-type natriuretic peptide reflects left ventricular hypertrophy and
      diastolic function in hypertension.
AB  - BACKGROUND: Hypertension is associated with changes in concentrations of
      vasoactive peptides and procollagen propeptides, but their relationships with
      left ventricular hypertrophy and cardiac function are unclear. METHODS: We
      measured plasma levels of atrial natriuretic peptide (ANP), its amino terminal
      propeptide (NT-proANP), B-type natriuretic peptide (BNP), endothelin-1 (ET-1),
      and serum levels of the aminoterminal propeptide of type I procollagen (PINP) and
      the aminoterminal propeptide of type III procollagen (PIIINP) and
      echocardiographic parameters in 97 patients with hypertension in the Anglo
      Scandinavian Cardiac Outcomes Trial. RESULTS: Median values (reference values) of
      the peptides were: ANP 11.2 (6.9-14.9) pmol/l, NT-proANP 351 (143-311) pmol/l,
      BNP 1.1 (0.4-7.2) pmol/l, ET-1 8.7 (1.2-5.0) pmol/l, PIIINP 2.8 (1.7-4.2)
      microg/l and PINP 29 (19-84) microg/l. Plasma BNP levels in patients with left
      ventricular hypertrophy (1.2 pmol/l) and patients with echocardiographic signs of
      diastolic dysfunction (1.5 pmol/l) were greater than those in patients without
      hypertrophy (0.7 pmol/l) and normal diastolic parameters (0.9 pmol/l) (p<0.05).
      BNP was the only biochemical parameter that independently predicted
      interventricular septal diastolic diameter (p<0.05), left ventricular mass index
      (p<0.01) and ratio of the velocity-time integrals of the E and A waves of the
      mitral inflow in a stepwise logistic regression analysis (p<0.05). CONCLUSIONS:
      The results show that BNP reflects the remodelling process in hypertension.

PMID- 15458693
TI  - Prevalence of metabolic syndrome in an Indian urban population.
AB  - OBJECTIVES: To determine prevalence of the metabolic syndrome using United States
      Adult Treatment Panel-3 (ATP-3) guidelines in an urban Indian population.
      METHODS: Randomly selected adults >20 years were studied using stratified
      sampling. Target study sample was 1800 with population proportionate distribution
      (men 960, women 840). Evaluation of anthropometric variables, blood pressure,
      fasting blood glucose and lipids was performed. Subjects (1123; response 62.4%)
      were examined, fasting blood samples were available in 1091 (532 men, 559 women)
      and analysed for prevalence of metabolic syndrome. Atherosclerosis risk factors
      were determined using the current guidelines. Metabolic syndrome was diagnosed
      when any three of the following were present: central obesity, raised
      triglycerides >/=150 mg/dl (>/=1.7 mmol/l), low high-density lipoprotein (HDL)
      cholesterol, blood pressure >/=130/>/=85 mm Hg, and diabetes or fasting glucose
      >110 mg/dl (>6.1 mmol/l). Intergroup comparisons were performed using t-test or
      chi-square test. RESULTS: Metabolic syndrome was present in 345 (31.6%) subjects;
      prevalence was 122 (22.9%) in men and 223 (39.9%) in women (p<0.001); the age
      adjusted prevalence was 24.9%, 18.4% in men and 30.9% in women. There was a
      significant age-related increase in its prevalence (Mantel-Haenzel chi(2) for
      trend p<0.05). Prevalence of components of metabolic syndrome in men and women
      was: central obesity (waist, men >102 cm, women >88 cm) in 116 (25.6%) and 246
      (44.0%); low HDL cholesterol (men<40 mg/dl, <1.0 mmol/l), women<50 mg/dl, <1.3
      mmol/l) in 292 (54.9%) and 504 (90.2%); high triglycerides >/=150 mg/dl (>/=1.7
      mmol/l) in 172 (32.3%) and 160 (28.6%); and impaired fasting glucose or diabetes
      in 90 (16.9%) and 90 (16.1%). The prevalence of physical inactivity,
      hypertension, hypercholesterolemia (>/=200 mg/dl, >/=5.2 mmol/l) and high LDL
      cholesterol (>/=130 mg/dl, >/=3.4 mmol/l) was greater in the metabolic syndrome
      group in both men and women (p<0.05). CONCLUSIONS: There is a high prevalence of
      metabolic syndrome in an urban Indian population. Focus of cardiovascular
      prevention should be at this high-risk group.

PMID- 15458694
TI  - Ischemic preconditioning: emerging evidence, controversy, and translational
      trials.
AB  - Protection against ischemia by ischemic preconditioning (IP) is seen in many
      tissues and organs. However, the preconditioning ischemia must precede lethal
      ischemia for this effect to occur, and the creation of ischemia to treat heart
      disease does not seem to be a realistic strategy. Accordingly, the underlying
      mechanisms that confer cardioprotection should be identified. Early studies
      revealed that IP causes two windows of cardioprotection, and subsequent efforts
      to detect cardioprotective factors have identified various triggers, mediators,
      and potent effectors of IP, such as endogenous receptor agonists (adenosine,
      catecholamines, bradykinin, and opioids), intracellular messengers [protein
      kinase C (PKC), p38MAPK, PI-3K, and PKA], ion channels such as KATP channels,
      enzymes including heat shock proteins (HSPs), superoxide dismutase (SOD), and 5'
      nucleotidase, and other factors [nitric oxide (NO), growth factors, free
      radicals, and products of the arachidonic acid cascade]. Some of these factors
      are involved in several different pathways and may have multiple roles in IP
      induced cardioprotection. Recently, however, certain problems have arisen such as
      controversies related to increasing knowledge and the relative lack of clinical
      studies in contrast to the intensive performance of basic studies. To overcome
      these problems, the latest studies have followed three major trends: (1)
      investigation of mechanisms to explain the current controversies, (2) detection
      of other unknown potent mechanisms, and (3) promotion of clinical trials based on
      the evidence from experimental studies in larger animals. Here, we summarize
      recent investigations on IP, emphasizing on the controversial issues and emerging
      factors, and discuss current research on the prevention or treatment of ischemic
      heart disease including some relevant clinical studies.

PMID- 15458695
TI  - Effect of pharmacological wash-out in patients undergoing exercise testing after
      acute myocardial infarction.
AB  - STUDY OBJECTIVES: Pharmacological therapy can reduce diagnostic and prognostic
      accuracy of exercise stress testing. However, the risk of withdrawing drugs early
      after myocardial infarction (MI) has not been established. We assessed safety and
      clinical implications of drug withdrawal in patients undergoing stress testing
      after uncomplicated MI. METHODS: A total of 362 MI patients underwent ECG Holter
      recording before and after withdrawing beta-blockers, calcium-antagonists and
      nitrates. QRS (QRS/h) and ventricular premature beats (VPB/h) count per hour,
      repetitive ventricular arrhythmias, ST segment changes and patient complaints
      were evaluated for reproducibility using kappa statistics and Bland-Altman
      method. RESULTS: No major complications occurred. Forty-three patients complained
      of >1 symptom on and 37 off therapy. QRS/h and VPB/h count were significantly
      (p<0.0001) higher off therapy but correlated with the corresponding values on
      therapy. A mean heart rate increase of 8 beats/min (agreement range -8 to +14
      beats/min) and a five-fold increase in VPB/h (agreement range -141 to +151) were
      observed after withdrawing therapy. Repetitive ventricular arrhythmias and ST
      changes were also more frequent off therapy but intra-patient reproducibility was
      poor: kappa 0.12 (95% confidence interval (CI) -0.01 to 0.25) for arrhythmias, 
      0.02 (95% CI -0.46 to 0.39) for ST depression and -0.01 (95% CI -0.66 to 0.64)
      for ST elevation. CONCLUSIONS: The withdrawal of therapy is well tolerated soon
      after uncomplicated MI; however, a generic but not individual risk of ventricular
      arrhythmias and/or transient myocardial ischemia has to be taken into account.

PMID- 15458696
TI  - Seasonal variation in morbidity and mortality related to atrial fibrillation.
AB  - OBJECTIVE: To determine whether there is seasonal variation in hospitalisations
      and deaths due to atrial fibrillation (AF) and to examine possible contributors
      to such variability. METHODS: We used the linked Scottish Morbidity Record
      scheme, which provides individualised morbidity and mortality data for the entire
      Scottish population. RESULTS: Between 1990 and 1996, there were a total of 33,582
      male and 34,463 female hospitalisations related to AF. Significantly more
      admissions occurred in winter compared to summer (P<0.0001). In women, the peak
      number of admissions (106 per day) occurred in December (12% more than average)
      and the lowest number (89) in June (6% less than average). The respective figures
      for men were 10% more (101), 2% less (90). In both sexes, the greatest variation
      occurred in those aged >85 years-peak winter rates being 35-39% higher than
      average. A similar phenomenon was evident in relation to mortality in these
      patients. The average number of men who died during December was 22% higher, and
      in August 12% lower, than average, P<0.001. In women, the equivalent figures were
      28% higher (December) and 14% lower (August), P<0.001. The winter peak of AF
      admissions did not, however, coincide with the lowest temperatures, and other
      factors such as seasonal variation in respiratory infection, may account for the
      monthly variation observed in hospitalisations for AF. CONCLUSIONS: There is
      substantial seasonal variation in AF hospitalisations and deaths, particularly in
      the elderly.

PMID- 15458697
TI  - Clinical in vivo calibration of pulse wave tissue Doppler velocities in the
      assessment of ventricular wall motion. A comparison study with M-mode
      echocardiography.
AB  - BACKGROUND: Pulsed Wave Tissue Doppler (PWTD) recording of myocardial velocities
      has been widely used for assessing ventricular function but the output trace has
      finite thickness that leads to potential ambiguity in determining velocity and
      timing. OBJECTIVE: To determine optimal method of measurement of PWTD traces by
      comparing them with those obtained from digitised M-mode recorded from the
      atrioventricular (AV) valve ring (septal, LV and RV free wall). METHODS: We
      studied 100 subjects, 49 normal and 51 with coronary artery disease (15 patients
      with reduced left ventricular wall motion, mean systolic amplitude of LV free
      wall 0.8+/-0.3 cm), mean age 53+/-15 years. We recorded AV ring motion using PWTD
      and M-mode echo techniques. PWTD velocity signals were measured separately at:
      outer, inner and mid-points of the envelope and compared with peak velocities
      obtained from digitised M-mode long axis. RESULTS: Peak systolic (S), early
      diastolic (E) and late diastolic (A) PWTD velocities at outer, inner and middle
      envelope correlated closely with the corresponding M-mode measurements at left,
      septal and right ventricular free wall. However, only the midpoint S and E wave
      PWTD signal velocities agreed numerically with those obtained by digitised M-mode
      velocities; S (left 6.56+/-1.80 vs. 6.54+/-1.91 cm/s N.S.); E (left 8.50+/-3.25
      vs. 7.65+/-3.30 cm/s N.S.). Agreement was somewhat less satisfactory for A wave;
      left 7.40+/-2.13 vs. 6.23+/-2.09 cm/s p<0.05. CONCLUSION: Atrioventricular valve
      ring echo provides an excellent in vivo calibration model for validating tissue
      Doppler velocity estimates. Since the mid-point of the envelope of the tissue
      Doppler signal is the most closely related value to that of the digitised M-mode,
      it may be recommended as a convention for routine practice.

PMID- 15458698
TI  - Ischemia Modified Albumin for the assessment of patients presenting to the
      emergency department with acute chest pain but normal or non-diagnostic 12-lead
      electrocardiograms and negative cardiac troponin T.
AB  - BACKGROUND: The diagnosis of myocardial ischemia in patients with acute chest
      pain at rest but non-diagnostic electrocardiograms (ECG) is problematic. Ischemia
      Modified Albumin (IMA) is a new biochemical marker of ischemia, which may be
      useful to characterise acute coronary syndrome (ACS) patients. METHODS: We
      studied 131 patients (mean age 58.5 years; 95 male) presenting to the emergency
      department with symptoms suggestive of ACS but with normal or non-diagnostic
      ECGs. Cardiac troponin T (cTnT) and IMA were measured within 3 h of last chest
      pain episode. Based on hospital diagnostic test results, patients were classified
      as having ACS or non-ischemic chest pain (NICP), by two independent cardiologists
      unaware of IMA results. RESULTS: Mean IMA levels (U/ml) were higher in patients
      with ACS (98.3+/-11) compared to patients with NICP (85.5+/-15); p<0.0001. IMA
      levels >93.5 U/ml demonstrated a sensitivity and specificity of 75% for the
      diagnosis of ACS; area under the receiver operator characteristic curve 0.78 (95%
      CI: 0.70-0.85). If we applied the manufacturer cutoff point of 85 U/ml, the
      sensitivity of IMA increased to 90.6% with a specificity of 49.3% (negative
      predictive value=84.6%). In combination with cTnT (6-12 h) (>0.05 ng/ml), the
      sensitivity increased to 92.2%. After multivariate analysis, IMA levels >85 U/ml
      (odds ratio=14.6 [95% CI 4.4-48.4]; p<0.0001), age and prior myocardial
      infarction were independent predictors of ACS. CONCLUSION: IMA may be a useful
      biomarker for the identification of ACS in patients presenting with typical acute
      chest pain but normal or non-diagnostic ECGs.

PMID- 15458699
TI  - Risk of the use of esmolol in the differential diagnosis of a wide QRS
      tachycardia.

PMID- 15458700
TI  - Effect of passive distraction on treadmill exercise test performance in healthy
      males using music.

PMID- 15458701
TI  - Brugada syndrome presenting with sustained monomorphic ventricular tachycardia.
AB  - Typically Brugada syndrome presents with either ventricular fibrillation or
      polymorphic ventricular tachycardia that may result in sudden death or syncope in
      patients without any structural heart disease. We report the case of a patient
      with Brugada syndrome who presented atypically with recurrent presyncope
      following physical exertion due to sustained monomorphic ventricular tachycardia,
      which appeared to be sensitive to both adenosine and catecholamine. He refused
      ICD implantation but remained asymptomatic on treatment with a beta-blocker.

PMID- 15458702
TI  - Acute compartment syndrome after transradial coronary angioplasty.

PMID- 15458703
TI  - Acute idiopathic pericarditis with transient constriction.

PMID- 15458704
TI  - The effect of mannan-binding lectin variant alleles on coronary artery reactivity
      in healthy young men.
AB  - Mannan-binding lectin (MBL) is a serum acute-phase protein and a complement
      component secreted by the liver. Its deficiency caused by point mutations in the
      MBL gene has recently been associated with severe atherosclerosis. In this study,
      we investigated the effect of MBL variant alleles on coronary artery reactivity,
      which is an early marker of coronary dysfunction and predicts the development of
      atherosclerosis and coronary artery disease. The study population consisted of 51
      apparently healthy, normo- or mildly hypercholesterolemic young men. Myocardial
      blood flow was measured at baseline and during adenosine-induced hyperemia with
      positron emission tomography (PET), and MBL genotyping was performed using
      restriction fragment-length polymorphism. As a result, MBL variant alleles had no
      effect on coronary artery reactivity. This finding suggests that MBL deficiency
      is not an independent risk factor for coronary dysfunction and early atherogenic
      changes but rather a co-factor in the development of atherosclerosis. Thus, the
      connection of MBL variant alleles with environmental risk factors in
      atherosclerosis should further be assessed.

PMID- 15458705
TI  - Atrio-ventricular block and ventricular tacchycardia induced by severe coronary
      spasm.

PMID- 15458706
TI  - QRS dispersion: an electrocardiographic index of systolic left ventricular
      dysfunction in patients with left bundle branch block.
AB  - The presence of complete left bundle branch block (LBBB) in patients with
      congestive heart failure has been proposed to be a factor that negatively affects
      left ventricular (LV) systolic function. The aim of this study was to evaluate
      the relative predictive value of QRS dispersion (QRSD) and QRS duration (QRSd) in
      relation to systolic performance of the left ventricle. The ejection fraction of
      130 consecutive patients with LBBB was evaluated by standard echocardiographic
      methods, whereas QRSd and QRSD were measured. It was demonstrated that QRSD in
      patients with complete LBBB is strongly related to LV contractility. We,
      therefore, suggest that this simple electrocardiographic index may serve as a
      useful screening test for detection of patients with LV systolic dysfunction.

PMID- 15458707
TI  - An unusual case of postoperative giant left ventricular pseudoaneurysm.
AB  - Pseudoaneurysms of the left ventricle are rare complications of acute myocardial
      infarction or cardiac surgery. Three years after aneurysmectomy of a true left
      ventricular aneurysm, a 66 years old man presented with clinical features of
      congestive heart failure. The echocardiography showed an extra large chamber next
      to the posterolateral region of the left ventricle with massive thrombus and
      severe mitral regurgitation. The diagnosis of pseudoaneurysm was made and was
      subsequently confirmed by radionuclid angiocardiography and surgical findings.
      Left ventricular pseudoaneurysm formation is a fairly unusual and serious
      complication of left ventricular aneurysmectomy with potential catastrophic
      results. Within the long period of time the pseudoaneurysm insidiously may become
      giant and may result in heart failure. Recognition of this rare complication of
      aneurysmectomy has therapeutic importance because surgical correction is
      necessary. Such pseudoaneurysm formation is easily recognized by two-dimentional
      echocardiography and radionuclic angiocardiogram. Careful echocardiographic
      examination is warranted for detecting such a complication in patients after
      cardiac surgery.

PMID- 15458708
TI  - Prognosis of coronary artery disease in young adults.

PMID- 15458709
TI  - Mechanism of spontaneous diminution of mitral regurgitation following
      percutaneous mitral valvuloplasty with the Inoue balloon.

PMID- 15458710
TI  - Valsalva sinus pseudoaneurysm causes acute myocardial infarction and stroke
      simultaneously.
AB  - Spontaneous Valsalva sinus pseudoaneurysm is a rare and highly lethal condition.
      Below we present a clinical case of a young woman with spontaneous Valsalva sinus
      pseudoaneurysm diagnosed presenting with acute myocardial infarction (AMI) and
      ischemic stroke.

PMID- 15458711
TI  - The methylenetetrahydrofolate reductase gene polymorphism (C677T) is associated
      with increased cardiovascular mortality in Hungary.
AB  - The gene for methylenetetrahydrofolate reductase (MTHFR) has two different
      alleles (C and T), where the T is associated with decreased enzyme activity,
      hyperhomocysteinaemia, and increased risk for thromboembolism in coronary heart
      disease (CHD). The study was conducted using a sample of 378 Hungarian newborn
      infants: 96 control subjects (age: 59.9+/-8.6 years) with chest pain and 315 CHD
      patients (61.4+/-7.5 years). All adult subjects had undergone coronary
      angiography. It can be concluded that the carriers of T allele with CHD died
      earlier due to myocardial infarction and the C allele with lower homocysteine
      level may provide protection against fatal coronary artery occlusion.

PMID- 15458712
TI  - Prolonged QT interval in acute pulmonary embolism.

PMID- 15458713
TI  - New onset transient lone atrial fibrillation in a healthy parturient: deja vu.

PMID- 15458714
TI  - Proceedings of the 41st Annual Meeting of the International Association of
      Forensic Toxicologists. November 16-20, 2003. Melbourne, Australia.

PMID- 15458715
TI  - Substance identification: the weak link in analytical toxicology.
AB  - Although substance identification is a key factor in analytical toxicology, it is
      amazing that the subject is receiving very limited and often inappropriate
      attention. With regard to the latter, a "confirmation" approach is usually
      chosen, which does not yield unambiguous identification. Moreover, the criteria
      for establishing a "positive match" leave much to be desired. These observations
      are corroborated when comparing some recent guidelines for qualitative analysis
      (issued for various forensic areas by SOFT/AAFS, NCCLS, NLCP, WADA and EU). Apart
      from showing substantial differences between them on pivotal issues, the
      guidelines contain various elements that appear scientifically incorrect and/or
      legally untenable. Also, the guidelines focus primarily on mass spectrometry (MS)
      and pay little or no attention to other identification possibilities (such as
      chromatographic techniques, either in combination with MS or as stand-alone
      techniques. Moreover, they do not offer alternatives in situations where access
      to MS is not available. One must conclude, therefore, that substance
      identification is a neglected and misunderstood domain in analytical toxicology.
      Rapid and concerted actions are needed to: (1) improve the general knowledge; (2)
      to define uniform strategies in the analytical approach and in the interpretation
      of the results; and (3) to set up and maintain suitable banks of reference
      substances and computerized data bases to allow unambiguous identification.

PMID- 15458716
TI  - Quantitative analysis of 33 benzodiazepines, metabolites and benzodiazepine-like
      substances in whole blood by liquid chromatography-(tandem) mass spectrometry.
AB  - A quantitative method using high-performance liquid chromatography-mass
      spectrometry (LC-MS, ion trap) after matrix supported liquid-liquid extraction is
      described for the simultaneous determination in whole blood of 33 benzodiazepines
      including metabolites and benzodiazepine-like substances. The limits of detection
      (LOD) range from 0.0001 to 0.0126 mg/l. Linearity is satisfactory for all
      compounds. The extraction recoveries for the benzodiazepines in whole blood are
      between 60 and 91%, desmethyldiazepam, OH-bromazepam and brotizolam excepted.
      Selectivity, accuracy and precision are satisfactory for clinical and forensic
      purposes.

PMID- 15458717
TI  - Confirmatory analysis for drugs of abuse in plasma and urine by high-performance
      liquid chromatography-tandem mass spectrometry with respect to criteria for
      compound identification.
AB  - Recently, high-performance liquid chromatography-tandem mass spectrometry
      (LC/MS/MS) has become a powerful tool for quantitative confirmatory analysis of
      drugs of abuse and has begun to spread in the field of forensic toxicology.
      Guidelines for confirmatory analysis by GC/MS and LC/MS/MS have been published
      recently by several organizations (WADA, IOC, SOFT, GTFCh, EU). However, these
      guidelines have not yet been included in procedures for drug analysis with
      LC/MS/MS. The prerequisites for forensic confirmatory analysis by LC/MS/MS with
      respect to EU guidelines are chromatographic separation, a minimum number of two
      MS/MS transitions to obtain the required identification points and predefined
      thresholds for the variability of the relative intensities of the MS/MS
      transitions (MRM transitions) in samples and reference standards. LC/MS/MS
      methods for determination of several classes of drugs of abuse including some
      basic drugs (opiates, stimulants), cannabinoids and some of their phase-I- and
      phase-II-metabolites (especially glucuronides) in urine and serum of drug abusers
      and/or crime offenders or victims have been developed and validated following
      current recommendations and are presented in this paper. At least two MRM
      transitions for each substance were monitored to provide sufficient
      identification of drugs, deuterated analogues of analytes were used as internal
      standards for quantitation where possible and chromatographic separation has been
      performed on reversed-phase columns with gradient elution. Validation data
      obtained and the application to real samples show that the requested criteria for
      confirmatory analysis of drugs of abuse by EU guidelines can be fulfilled with a
      total number of four identification points by LC/MS/MS methods using a triple
      quadrupole mass spectrometer. Furthermore, the methods are sufficiently sensitive
      to meet current requirements for confirmatory analysis of drugs of abuse in
      driving under the influence of drugs (DUID) cases established by the Society of
      Toxicological and Forensic Chemistry (GTFCh).

PMID- 15458718
TI  - Liquid chromatography-tandem mass spectrometry determination of loperamide and
      its main metabolite desmethylloperamide in biological specimens and application
      to forensic cases.
AB  - A liquid chromatographic mass spectrometric (LC/MS/MS) method has been developed
      for the determination of loperamide in whole blood and other biological
      specimens. The procedure involves liquid-liquid extraction of loperamide,
      desmethylloperamide and methadone-D3 (internal standard) with butyl acetate.
      Confirmation and quantification was done by positive electrospray ionisation with
      a triple quadrupole mass spectrometer operating in multiple reaction-monitoring
      (MRM) mode. Two MRM transitions of each compound were established and
      identification criteria were set up based on the ratio of the responses between
      the two MRM transitions of each compound. The standard curves were linear over a
      working range of 0.1-500 microg/kg for all transitions. The limit of
      quantification was 0.1 microg/kg in whole blood. The repeatability and
      reproducibility within the laboratory expressed by relative standard deviation
      were less than 5 and 11%, respectively, and the accuracy was better than 9%. The
      method was developed to examine a feces sample from a child whose mother was
      suspected of Munchausen syndrome by proxy and it proved to be suitable for
      forensic cases being simple, selective and reproducible. The method was also
      applied for a case investigation involving a overdose of loperamide.

PMID- 15458719
TI  - Detection of cocaine and cocaethylene in sweat by solid-phase microextraction and
      gas chromatography/mass spectrometry.
AB  - In the present work, a semi-quantitative method was developed to detect
      simultaneously cocaine (COC) and cocaethylene (CE) (transesterification product
      of the coingestion of COC with ethanol) in sweat. Sweat samples were collected by
      means of a non-occlusive sweat patch device supplied by PharmChek. The method was
      based on the dissolution of COC and CE incorporated into the patch, with 0.2 M
      sodium acetate buffer (pH 5.0) and the extraction of the analytes by solid-phase
      microextraction (SPME). Gas chromatography/mass spectrometry (GC-MS) was used to
      detect the analytes in selected ion monitoring mode (SIM). The method showed to
      be very simple, rapid and sensitive. The limits of detection were 5 ng/ml for COC
      and CE (12.5 ng/patch). Good inter and intra-assay precision was also observed
      (coefficient of variation <8%) with the use of deuterated internal standards.

PMID- 15458720
TI  - Determination of MDMA, MDEA and MDA in urine by high performance liquid
      chromatography with fluorescence detection.
AB  - This paper describes the development and validation of analytical methodology for
      the determination of the use of MDMA, MDEA and MDA in urine. After a simple
      liquid extraction, the analyses were carried out on a high performance liquid
      chromatography (HPLC) in an octadecyl column, with fluorescence detection. The
      mobile phase using a sodium dodecyl sulfate ion-pairing reagent allows good
      separation and efficiency. The method showed good linearity and precision.
      Recovery was between 85 and 102% and detection limits were 10, 15 and 20 ng/ml
      for MDA, MDMA and MDEA, respectively. No interfering substances were detected
      with fluorescence detection.

PMID- 15458721
TI  - Validated assay for the determination of markers of illicit heroin in urine
      samples for the control of patients in a heroin prescription program.
AB  - A fully validated procedure for the simultaneous determination of morphine (MOR),
      morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), 6-acetylmorphine
      (6AM), codeine (COD), codeine-6-glucuronide (C6G), acetylcodeine (AC), noscapine
      (NOS) and papaverine (PAP) based on liquid chromatography followed by
      electrospray mass spectrometry applying multiple reaction monitoring (LC-ESI
      MS/MS) in urine samples is described. The extraction was carried out on a Zymark
      Rapid Trace Workstation using C18 solid-phase extraction cartridges. The
      separation was performed in 19 min on an Agilent 1100 HPLC system, using a
      Phenomenex C18 AQUA column (4 microm, 150 mm x 2 mm), which is coupled with an
      Applied Biosystems API 2000 mass spectrometer. Deuterated analogues were used as
      internal standards. The limits of detection were in the range of 0.1 ng/ml (PAP)
      to 7.4 ng/ml (M6G), the coefficients of correlation were higher than 0.996, the
      precisions ranged from 3% to 12% and the absolute recoveries were between 45%
      (M3G) and 98% (MOR). Analyses of samples from patients of a heroin prescription
      program demonstrated the usefulness of the procedure for the analytical
      differentiation between prescribed synthetic heroin (diamorphine) use and non
      prescription heroin abuse on the basis of urine analysis. After the ingestion of
      pharmaceutical heroin only general markers for heroin use were detected, which
      are MOR, M3G, M6G and 6AM, respectively. When illicit heroin was abused,
      additionally to further general markers (COD, C6G) specific markers for non
      prescription heroin abuse (AC, NOS, PAP) were found. However, it must be kept in
      mind that only AC may be regarded as absolute specific marker of non-prescription
      heroin, because all other compounds may appear in urine after ingestion of opiate
      alkaloids containing medicines or foods (e.g. poppy seeds). Therefore, patients
      of a heroin prescription program should be advised not to ingest such products.

PMID- 15458722
TI  - Kinetic characteristics and toxic effects of benzalkonium chloride following
      intravascular and oral administration in rats.
AB  - Kinetic characteristics and toxic effects of benzalkonium chloride (BZK)
      following injection via jugular vein (JV), femoral artery (FA) and oral
      administration (PO) were experimentally investigated using rats. The BZK
      concentrations in blood and tissues (lung, liver and kidney) were determined by
      high-performance liquid chromatography with solid phase extraction. Toxic doses
      of 15 and 250 mg/kg of BZK were used for intravascular (JV and FA) and PO
      administration, respectively. The fatal effects appeared soon after the dose in
      JV-rats, while delayed in FA- or PO-rats. The blood BZK concentrations and the
      elimination half-lives were similar between JV- and FA-rats, while the
      distribution of BZK in tissues was slightly different. In PO administration, the
      rats that aspirated BZK into their lungs had some symptoms, while the rats that
      did not aspirate BZK appeared to be normal. The BZK concentrations in blood and
      tissues were significantly higher in the aspirated PO-rats. The toxic degree of
      BZK was correlated with the BZK concentration in orally dosed rats. Lung and
      kidney had higher BZK concentrations compared to blood or liver, and they could
      be the target organs of BZK.Keyword: Benzalkonium chloride

PMID- 15458723
TI  - Testing for zolpidem in oral fluid by liquid chromatography-tandem mass
      spectrometry.
AB  - The purported enhancement of sexuality, coupled with a possible abrupt coma
      inducing effect and ease of administration in spiked drinks have resulted in the
      use of hypnotics to facilitated a sex offence. Among these compounds, zolpidem
      possesses amnesic properties, is short-acting and can rapidly impair an
      individual. In order to document zolpidem exposure, we have developed an original
      analytical method in oral fluid. 500 microl of oral fluid was added to 500 microl
      pH 7.6 Soerensen buffer was extracted by 2 ml dichloromethane in presence of 5 ng
      diazepam-d5, used as internal standard. An aliquot of the extract was injected
      into a 5 microm Novapak C18 column (150 mm x 2.1 mm). Reversed-phase separation
      was achieved in 6 min, under isocratic conditions (90% acetonitrile, 10% 2 mM
      ammonium formate pH 3.6) at a flow rate of 150 microl/min. Detection was achieved
      by tandem mass spectrometry. Molecular ions (m/z 308 and 290 for zolpidem and the
      IS, respectively) were selected in Q1 and the corresponding daughter ions (m/z
      235 and 263 for zolpidem and m/z 154 and 198 for the IS) were detected in Q3
      after collision with argon. Linearity was observed for zolpidem concentrations
      ranging from 0.2 to 100 ng/ml, and the assay was capable of detecting 0.05 ng/ml.
      Oral fluid was collected for 480 min after oral zolpidem administration of 10 mg
      to 2 subjects. In both cases, zolpidem was detectable (0.4 ng/ml) after 15 min
      intake. Peak zolpidem concentrations were obtained at 150 min (53.5 ng/ml) and
      180 min (75.7 ng/ml), respectively. Oral fluid tested positive for zolpidem for
      over 8 h (9-15 ng/ml).

PMID- 15458724
TI  - Detection of anti-diabetics in equine plasma and urine by liquid chromatography
      tandem mass spectrometry.
AB  - AIM: Anti-diabetics such as sulfonylurea and thiazolidinedione derivatives are
      hypoglycemic drugs used for the treatment of diabetes. However, they can also be
      used as a stopper in horseracing. This paper describes a convenient method for
      the separation and simultaneous detection of 10 anti-diabetic drugs (namely
      glipizide, glibenclamide, glimepiride, gliclazide, tolazamide, tolbutamide,
      nateglinide, repaglinide, rosiglitazone and pioglitazone) in equine plasma and
      urine by LC-MS-MS. METHOD: The anti-diabetics were isolated from equine plasma
      and urine by liquid-liquid extraction with 1,2-dichloroethane at acidic pH, and
      analysed by LC-MS-MS in the positive electrospray ionisation mode. Separation of
      10 anti-diabetic drugs was achieved with a reversed phase C8 column using a
      mixture of aqueous ammonium formate (pH 3.0, 10 mM) and methanol as the mobile
      phase. RESULTS: Detection and confirmation of the 10 anti-diabetic drugs at 10
      ng/mL each in equine plasma and equine urine were achieved by full-scan MS-MS.
      All of these drugs were detected consistently at this concentration in spiked
      samples of different plasma and urine (n = 15 each). No significant matrix
      interferences were observed at the expected retention times of the targeted ions
      in blank urine samples (n = 30). This method has been used successfully in the
      analysis of drug-administration samples as well as official racing samples.
      CONCLUSION: An LC-MS-MS method has been developed for the simultaneous detection
      of 10 anti-diabetics in equine plasma and urine. This method can be used to
      detect the abuse of anti-diabetic drugs in racehorses.

PMID- 15458725
TI  - Detection of stanozolol and its metabolites in equine urine by liquid
      chromatography-electrospray ionization ion trap mass spectrometry.
AB  - The equine phase I and phase II metabolism of the synthetic anabolic steroid
      stanozolol was investigated following its administration by intramuscular
      injection to a thoroughbred gelding. The major phase I biotransformations were
      hydroxylation at C16 and one other site, while phase II metabolism in the form of
      sulfate and beta-glucuronide conjugation was extensive. An analytical procedure
      was developed for the detection of stanozolol and its metabolites in equine urine
      using solid phase extraction, acid solvolysis of phase II conjugates and analysis
      by positive ion electrospray ionization ion trap LC-MS.

PMID- 15458726
TI  - Protopine alkaloids in horse urine.
AB  - Protopine was extracted from Fumaria officinalis and purified by column
      chromatography. Urine samples were collected from horses and a human volunteer
      that had been administered either F. officinalis or protopine free base. Plant
      and urine samples were acetylated and analysed by GCMS after solid-phase
      extraction (SPE). The urinary metabolites of protopine were identified as
      4,6,7,13-tetrahydro-9,10-dihydroxy-5-methyl-benzo[e]-l,3-benzodioxolo [4,5-1][2]
      benzazecin-12(5H)-one, 4,6,7,13-tetrahydro-10-hydroxy-9-methoxy-5-methyl-benzo[e]
      1,3-benzodioxolo[4,5-1][2] benzazecin-12(5H)-one and 4,6,7,13-tetrahydro-9
      hydroxy-10-methoxy-5-methyl-benzo[e]-1,3-benzodioxolo[4,5-l][2] benzazecin-12(5H)
      one, chelianthifoline, isochelianthifoline and 2-O-desmethylchelianthifoline. The
      metabolic formation of the tetrahydroprotoberberines by closure of the bridge
      across N5 and C13 is rate limited and protopine-like metabolites accumulate only
      when the route is overloaded. Metabolism was qualitatively similar in the horse
      and human.

PMID- 15458727
TI  - 3-Methoxytyramine as an indicator of dopaminergic manipulation in the equine
      athlete.
AB  - The influence of sampling variables on the concentration of the dopamine
      metabolites 3-methoxytyramine (3MT), dihydroxyphenylacetic acid (DOPAC) and
      homovanilic acid (HVA) was examined in equine urine. A logarithmic transformation
      of the data for all horses gave distribution which approximated the normal
      distributions for each metabolite. The mean urinary concentration of 3 MT in
      horses was 214 ng/mL and the application of a threshold with a probability of 1
      in 10,000 gave an actionable level of 4 microg/mL. Environmental variables were
      not forensically significant in determining the population distribution. HVA was
      not found to be a reliable indicator of dopamine or levodopa administration.

PMID- 15458728
TI  - Setting the positive expiratory-end pressure-FIO2 in acute lung injury/acute
      respiratory distress syndrome.
AB  - Airspace collapse is a hallmark of parenchymal lung injury. Strategies to reopen
      and maintain patency of these regions offer three advantages: improved gas
      exchange, less ventilator-induced lung injury, and improved lung compliance.
      Elevations in intrathoracic pressure to achieve these goals, however, may
      overdistend healthier lung regions and compromise cardiac function. Positive end
      expiratory pressure is a widely used technique to maintain alveolar patency, but
      its beneficial effects must be balanced against its harmful effects. Mechanical
      approaches to achieve this balance are clinically difficult to do. Thus gas
      exchange algorithms with modest PaO2 goals are commonly used today. Recruitment
      maneuvers and long inspiratory time strategies may be useful adjuncts.

PMID- 15458729
TI  - The "best" tidal volume for managing acute lung injury/acute respiratory distress
      syndrome.
AB  - An inappropriate tidal volume setting can overstretch and injure the lung.
      Maximal stretch, tidal stretch, frequency of stretch, and rate of stretch are all
      implicated in such injury. Moreover, the stretch injury produces systemic injury
      by liberating cytokines and translocating bacteria in the lung. Clinical trials
      have shown that limiting maximal and tidal stretch improves outcomes, even if gas
      exchange is partially compromised. Current strategies should focus on limiting
      tidal and maximal stretch as much as possible.

PMID- 15458730
TI  - Lessons from the ARDS network ventilator trial design controversy.
AB  - This article reviews the available published literature on the ARDSnet and
      summarizes the debate that occurred over the major ARDSnet trials. It discusses
      the challenges its organizers, supporters, and detractors faced. It reviews how
      uncertainty in research evolves and how it affects large trials of national or
      international scope. It also considers how the outcome of a scientific
      disagreement is shaped by the science and by how the debate is framed. The
      authors hope to illustrate some of the obstacles to performing outcome studies
      and clinical trials involving critically ill patients with complex syndromes that
      currently lack effective treatments.

PMID- 15458731
TI  - What is the role of high-frequency ventilation in adult respiratory distress
      syndrome?
AB  - The goal of positive-pressure mechanical ventilation is to provide respiratory
      support to a patient while allowing the underlying diseased lungs to heal.
      Research using both animal models and humans suggests that positive-pressure
      ventilation can injure the lung through both overdistension and under
      recruitment. Theoretically,the ultimate lung-protective strategy would consist of
      very small tidal volumes to avoid pressure swings while maintaining alveolar
      recruitment. High-frequency ventilation provides such a strategy of mechanical
      ventilation. This article examines the utility of using high-frequency modes of
      mechanical ventilation in supporting the patient with ARDS.

PMID- 15458732
TI  - Therapy for ventilator-associated pneumonia: what works, what doesn't.
AB  - Ventilator-associated pneumonia is a common cause of morbidity and mortality in
      critically ill patients. Inappropriate initial antimicrobial therapy is
      associated with poor outcome. An initial aggressive strategy using broad-spectrum
      antibiotics based on the local distribution of pathogens, patient risk factors,
      and antimicrobial characteristics; followed by focused therapy based on
      microbiologic studies, will help minimize the chance of inappropriate therapy and
      the emergence of resistance.

PMID- 15458733
TI  - Forehead oximetry in critically ill patients: the case for a new monitoring site.
AB  - Pulse oximetry is a ubiquitous monitor in anesthesia and critical care and is
      often considered the fifth vital sign. Under conditions of normal perfusion and
      temperature, the finger probe is the most common and effective sensor. In the
      presence of hypotension, hypoperfusion,and hypothermia, however, the finger
      sensor is often unable to detect a pulsatile signal. Another site and sensor are
      necessary to monitor these patients effectively. This article describes the
      search for this site, the choice of the forehead, and preliminary data regarding
      the use of this sensor site.

PMID- 15458734
TI  - Mechanical ventilation in orbit: emphasis on closed-loop ventilation.
AB  - As part of a Crew Health Care Maintenance System onboard the International Space
      Station, the National Aeronautics and Space Administration has included a
      Respiratory Support Pack (RSP) to resuscitate or sustain a crew member with an
      acute impairment in pulmonary function. This article provides a critical
      appraisal of the RSP and of current strategies for mechanical ventilation in
      space. Various closed-loop ventilation strategies are reviewed,and their
      appropriateness for respiratory support in space is explored. Recommendations are
      made for enhancing and upgrading the current RSP to provide an injured crew
      member with the best possible chance of survival.

PMID- 15458735
TI  - Emergency airway management in orbit: an evidence-based review of possibilities.
AB  - It is likely that the first responder to a medical emergency in space will be a
      nonphysician. Terrestrial experience has shown that even under optimal conditions
      experienced clinicians can have difficulty establishing an airway. Establishing
      and maintaining a patent airway is essential to ensuring a successful outcome
      from cardiopulmonary resuscitation or respiratory failure secondary to trauma or
      acute illness. A patent airway is required to provide a pathway for ventilation
      and oxygenation. For minimally trained care providers the airway will also be the
      first route of administration of resuscitative pharmacologic agents. It is
      therefore of paramount importance that the method for securing and airway permit
      a successful outcome when used by nonphysician crewmembers during medical
      emergencies in space. This article evaluates airway management in the
      microgravity environment and applies to both the International Space Station and
      the Space Shuttle, whether operating independently or docked.

PMID- 15458738
TI  - Controlled ovarian hyperstimulation--an inflammatory state.
AB  - OBJECTIVE: Controlled ovarian hyperstimulation (COH) is apparently a key factor
      in the success of in vitro fertilization-embryo transfer. One of the major
      complications of COH is severe ovarian hyperstimulation syndrome (OHSS), which
      may be attributable to a massive increase in systemic inflammatory cytokines or
      to neutrophil activation. The aim of the present review was to investigate the
      role of COH in the induction of an inflammatory response. METHODS: Major studies
      that have reported on the association between COH and inflammation were
      identified through MEDLINE searches and the published literature. RESULTS:
      Several inflammatory mediators, namely, C-reactive protein and leukocyte and
      endothelial selectins, showed a significant increase after human chorionic
      gonadotropin (hCG) administration in vivo, reflecting an inflammatory state, and
      neutrophil and endothelial activation, respectively. On the other hand, hCG
      showed a direct depressive effect on mononuclear cells in vitro. Because the
      development of OHSS almost always follows hCG administration, the negative effect
      of hCG on peripheral mononuclear cells indicates that it probably causes OHSS by
      an indirect mechanism. CONCLUSION: We suspect that hCG stimulates the ovaries to
      produce and secrete a still unknown intermediate factor, which in turn activates
      inflammatory processes that may lead to an increase in capillary permeability.

PMID- 15458739
TI  - The role of matrix degrading enzymes and apoptosis in rupture of membranes.
AB  - Prematurity is the third leading cause of perinatal death, and preterm premature
      rupture of the membranes (pPROM) is associated with approximately 20-50% of all
      preterm births. The etiologic factors described for pPROM and preterm labor (PTL)
      are the same, although the clinical presentation (pPROM vs PTL) differs among
      patients. The reason for this disparity is unknown and poses a therapeutic
      dilemma. Several etiologic factors have been described for PTL and pPROM. PTL and
      pPROM are associated with overwhelming host inflammatory response. Many of these
      pro-inflammatory factors (inflammatory cytokine release) are common in both
      conditions; however, the clinical presentation differs. The objective of this
      review is to explain the differential expression pattern of matrix
      metalloproteinases (MMPs) and pro-apoptotic elements in human fetal membranes in
      pPROM and PTL and how they interact to present different clinical outcomes during
      pregnancy.

PMID- 15458740
TI  - Mechanisms of renal vasodilation and hyperfiltration during pregnancy.
AB  - Glomerular filtration rate (GFR) and renal plasma flow (RPF) increase by 40-65%
      and 50-85%, respectively, during normal pregnancy in women. Studies using the
      gravid rat as a model have greatly enhanced our understanding of mechanisms
      underlying these remarkable changes in the renal circulation during gestation.
      Hyperfiltration appears to be almost completely due to the increase in RPF, the
      latter attributable to profound reductions in both the renal afferent and
      efferent arteriolar resistances. The major pregnancy hormone involved is relaxin.
      The mediators downstream from relaxin include endothelin (ET) and nitric oxide
      (NO). New evidence indicates that relaxin increases vascular gelatinase activity
      during pregnancy, thereby converting big ET to ET(1-32), which leads to renal
      vasodilation, hyperfiltration, and reduced myogenic reactivity of small renal
      arteries via the endothelial ET(B) receptor and NO. Whether the chronic volume
      expansion characteristic of pregnancy contributes to the maintenance of
      gestational renal changes requires further investigation. Additional studies are
      also needed to further delineate the molecular basis of these mechanisms and,
      importantly, to investigate whether they apply to women.

PMID- 15458741
TI  - Absence of robust ischemic preconditioning by five 1-minute total umbilical cord
      occlusions in fetal sheep.
AB  - OBJECTIVE: To determine to what extent a series of five 1-minute total umbilical
      cord occlusions, intended to induce ischemic preconditioning (IP), affects the
      physiologic responses to a 10-minute total umbilical cord occlusion (damaging
      insult [DI]) 1 hour later and provides cardio- and neuroprotection. METHODS: In
      14 chronically catheterized late gestation fetal sheep (127-131 days' gestation),
      we performed a 10-minute total umbilical cord occlusion (DI), preceded by a
      series of five 1-minute total cord occlusions with 2-minute intervals (5CO, n =
      7) or sham occlusions (n = 7) 1 hour prior to DI. RESULTS: The 5CO induced a
      reduction in the arterial partial pressure of oxygen (Po(2)) from 21 +/-1 to 14
      +/-3 Torr, arterial O(2) content from 6.9 +/- 0.4 to 3.1 +/- 0.7 vol%, and
      increases in the partial pressure of carbon dioxide (Pco(2)) from 46 +/- 2 to 58
      +/- 3 Torr, and [H(+)] from 43 +/- 1 to 54 +/- 2 nM. 5CO reduced fetal heart rate
      from 178 +/- 6 to 151 +/- 6 beats per minute (bpm), and increased arterial
      pressure from 45 +/- 1 to 57 +/- 2 mmHg, cerebral blood flow (CBF) from 100 +/- 3
      to 129 +/- 10%, and cerebral heat production (H(brain)) from 25 +/- 2 to 29 +/-
      1% degrees C. The responses to DI were not significantly different between the
      groups without and with 5CO; values for Po(2) were 5.6 +/- 1.5 and 5.8 +/- 1.9
      Torr, O(2) content 0.6 +/- 0.1 and 0.8 +/- 0.1 vol%, lactate 10.7 +/- 0.7 and
      10.8 +/- 0.7 mM, fetal heart rate 97 +/- 5 and 87 +/- 8 bpm, mean arterial
      pressure 22 +/- 3 and 21 +/- 2 mmHg, CBF 50 +/- 10 and 36 +/- 5%, and H(brain)
      7.0 +/- 1.4 and 5.9 +/- 1.1% degrees C, respectively, except for Pco(2) (126 +/-
      4 and 112 +/- 2 Torr) and [H(+)] (126 +/- 3 and 114 +/- 3 nM). Histologic proof
      of cardio- or neuroprotection by 5CO could not be obtained because five fetuses
      died before they were to be killed at day 3 after the experiment; two fetuses in
      the 5CO group demonstrated major histologic damage of myocardium and brain.
      CONCLUSION: In the late gestation fetal sheep, a series of five 1-minute total
      umbilical cord occlusions did not result in major changes in physiologic
      responses to a hypoxic-ischemic DI 1 hour later. In addition, the procedure did
      not result in robust cardio- and neuroprotection, in contrast to IP reported in
      adults.

PMID- 15458742
TI  - 17beta-estradiol up-regulates prostacyclin production in cultured human uterine
      myometrial cells via augmentation of both cyclooxygenase-1 and prostacyclin
      synthase expression.
AB  - OBJECTIVE: To investigate whether 17beta-estradiol elevates prostacyclin (PGI(2))
      production in human myometrial cells in the middle of gestation. METHODS: The
      concentration of 6-keto-PGF(1alpha), a stable metabolite of PGI(2), in the
      culture medium was assessed using enzyme-linked immunosorbent assay (ELISA).
      Western blot analysis and quantitative reverse-transcriptase polymerase chain
      reaction (RT-PCR) using TaqMan (Applied Biosystems, Foster City, CA) technology
      were performed to evaluate the expression of cytosolic phopholipase A(2)
      (cPLA(2)), cyclooxygenase-1 (COX-1), COX-2, and prostacyclin synthase (PGIS) in
      cultured human myometrial cells prepared from second trimester pregnant women (n
      = 3) after stimulation with 17beta-estradiol. RESULTS: Treatment with 17beta
      estradiol (4-400 nM) dose-dependently elevated PGI(2) secretion from cultured
      human myometrial cells. Western blot analysis detected cPLA(2) and COX-1 and PGIS
      protein expression in the cultured human myometrial cells; however, COX-2 protein
      expression was below the detection sensitivity. Stimulation with 40-nM 17beta
      estradiol significantly up-regulated protein and mRNA expression of both COX-1
      and PGIS. CONCLUSION: 17beta-Estradiol from placenta may contribute to the
      augmentation of PGI(2) production in the human myometrium in the middle of
      gestation via up-regulation of both COX-1 and PGIS expression.

PMID- 15458743
TI  - Heme oxygenase-1 mediates up-regulation of adhesion molecule expression induced
      by peroxynitrite in endothelial cells.
AB  - OBJECTIVE: Endothelial cell (EC) activation with up-regulation of cellular
      adhesion molecule (CAM) expression is a pathophysiologic feature in preeclampsia
      (PE). Enhanced peroxynitrite formation in the vasculature of women with PE was
      also reported. This study was to test whether EC oxidative stress induced by
      peroxynitrite could up-regulate EC CAM expression, and whether heme oxygenase-1
      (HO-1) has protective effects on this peroxynitrite-induced cellular response.
      METHODS: Confluent ECs were stimulated with 3-morpholinosydnonimine-HCl (SIN-1, a
      peroxynitrite generator) alone or combined with Mn(III) tetrakis (1-methyl-4
      pyridyl) porphyrin pentachloride (MnTMPyP, a peroxynitrite scavenger) up to 4
      hours. EC surface protein expressions for ICAM, VCAM, P-selectin, and E-selectin
      were measured by colorimetric assay. ECs were also treated with Sn(IV)
      mesophorphyrin IX dichloride (SnMP, a HO-1 inhibitor) to determine if HO-1 was
      involved in the increased CAM expression in stressed cells. Protein and mRNA
      expressions for HO-1 were determined by Western blot analysis and reverse
      transcriptase polymerase chain reaction (RT-PCR). Data are presented as the mean
      +/- SE and analyzed by analysis of variance (ANOVA). RESULTS: Endothelial CAM
      expressions for VCAM, P-selectin, and E-selectin, but not ICAM, were
      significantly increased in SIN-1-treated ECs. Protein and mRNA expressions for HO
      1 were also up-regulated in cells treated with SIN-1. MnTMPyP blocked both mRNA
      and protein expressions for HO-1, whereas SnMP only blocked HO-1 protein
      expression. Both MnTMPyP and SnMP abolished SIN-1-induced up-regulation of VCAM,
      P-selectin, and E-selectin expression in ECs. CONCLUSIONS: Peroxynitrite-induced
      EC oxidative stress produces differential effects on CAM expression, which may be
      mediated by HO-1 regulation. Our results suggest that increased peroxynitrite
      formation in the maternal vasculature may contribute to the increased CAM
      expression and enhanced neutrophil-endothelial interaction associated with PE.

PMID- 15458744
TI  - Taurine transport into fetal cord blood cells: inhibition by cyclosporine A.
AB  - OBJECTIVES: Pregnant women undergoing long-term organ transplant treatment have
      an increased incidence of delivering infants with intrauterine growth restriction
      (IUGR). Cyclosporine A is used as an immunosuppressant in such women and indirect
      evidence suggests that IUGR might result from an effect of cyclosporine A on
      amino acid transport by the placenta. In this study we tested the hypothesis that
      the transport of an essential amino acid, taurine, by fetal tissue other than the
      placenta is modulated by cyclosporine A. METHODS: Cord blood cells (CBCs) were
      used to test this hypothesis as an easily obtainable fetal tissue. Transport of
      taurine into CBCs was measured using standard tracer flux assays. RESULTS: Uptake
      of [(3)H] taurine by CBCs was linear over 15 minutes (76.2 +/- 16.6 fmol/10(6)
      cells/min, mean +/- SEM, n = 6) and inhibitable by 10 mM beta-alanine, a
      substrate of the system-beta taurine transport protein (6.7 +/- 1.0 fmol/10(6)
      cells/min, n = 6, P <.05, paired Student t test). Pre-incubation with
      cyclosporine A (5 microM) inhibited [(3)H] taurine uptake by 29.3%-5.3% (n = 8, P
      <.05, paired Student t test). CONCLUSIONS: These data show that amino acid
      transport via system-beta can be measured in CBCs and may be a useful model for
      amino acid transport studies in fetal cells. We also show that system-beta was
      inhibited by the immunosuppressant, cyclosporine A. This suggests that the
      increased incidence of IUGR reported in mothers treated with cyclosporine A may
      be due partially to effects on taurine uptake into fetal cells outside the
      placenta.

PMID- 15458745
TI  - Tissue-level bioelectrical signals as the trigger for uterine contractions in
      human pregnancy.
AB  - OBJECTIVE: To investigate the relationship between tissue-level bioelectrical
      signals and tension development during oxytocin-stimulated contractions of human
      myometrium. METHODS: We performed in vitro muscle bath experiments on human
      myometrial tissue strips while simultaneously monitoring bioelectrical activity
      with two loose-contact electrodes. Tissue was obtained by myometrial biopsy from
      term pregnant women at the time of cesarean delivery. Tissue strips (1 x 1 x 10
      mm) were hung vertically and maintained in culture in media while suspending a
      400-mg weight. The tissue exhibited strong isometric contractions in response to
      5-nM oxytocin even after 10 to 14 days in culture. The electrodes were separated
      by 4 mm, and allowed us to distinguish between local and tissue-level
      bioelectrical signals. Electrical activity was monitored using two, independent
      AC-coupled amplifiers. RESULTS: Following exposure to oxytocin, the tissue
      contracted periodically every 3.5 to 6 minutes, with each contraction lasting 50
      to 60 seconds. Near the beginning of each contraction, synchronized spike-like
      bioelectrical signals were observed in both channels. These bioelectrical signals
      from each electrode lasted approximately 2 seconds and demonstrated unique
      fingerprints that were repetitive and remarkably similar over 18 contractions. In
      each of the contractions, the onset of rapid force increases was synchronized
      with the bioelectrical signals. Cell recruitment continued during the plateau
      phase of each contraction even though other tissue-level bioelectrical signals
      were not observed. CONCLUSION: These findings suggest that the trigger for the
      initiation of each contraction is a tissue-level bioelectrical event, and some
      cells are initially recruited to participate in each contraction by excitation
      contraction coupling. After the initial phase of the contraction, cells are
      recruited by a nonelectrical mechanism.

PMID- 15458746
TI  - Neurodevelopmental outcome of very low birth weight infants after multiple
      courses of antenatal corticosteroids.
AB  - OBJECTIVE: To determine if two or more courses of antenatal corticosteroids are
      associated with neurodevelopmental impairment. METHODS: All infants born at
      Northwestern Memorial Hospital between 1995 and 1998, who met the following
      criteria, were identified: birth weight < or = 1500 g, gestational age between 24
      and 34 weeks, recipient of antenatal corticosteroids, and subsequent
      neurodevelopmental evaluation in multidisciplinary developmental evaluation
      clinic. The outcomes of these infants were compared according to degree of
      corticosteroid exposure. This study had 80% power to detect a difference in the
      mental development index score of 10% or a relative risk of neurodevelopmental
      delay of 2.5 in the group receiving at least two courses of corticosteroids.
      RESULTS: Ninety-three infants were exposed to less than two full courses and 33
      infants were exposed to at least two full courses of corticosteroids. The mean
      duration of follow-up was similar in the two groups (25 months vs 30 months,
      respectively, P >.05). The two groups had similar neonatal outcomes, and had no
      differences in any measures of neurodevelopmental outcome on follow-up.
      CONCLUSION: Repeated courses of antenatal corticosteroids are not associated with
      increased incidence of abnormalities on subsequent neurodevelopmental outcome
      measures.

PMID- 15458747
TI  - Antigen-presenting cells in human endometrium during the menstrual cycle compared
      to early pregnancy.
AB  - OBJECTIVE: Human endometrium and early pregnancy decidua harbor a considerable
      and diverse population of antigen-presenting cells (APC). Changes in the number
      and distribution of macrophages and dendritic cells (DC) could point to a
      possible role of these immunocompetent cells in implantation and success of early
      pregnancy. METHODS: Uterine tissue was obtained from 22 women undergoing
      hysterectomy for bleeding disorders or dysmenorrhea and from 11 women undergoing
      legal abortion. Tissue was investigated with antibodies against CD14, CD68, CD83,
      DC-SIGN, Ki-67, and human leukocyte antigen (HLA)-DR using single and double
      immunohistochemical staining techniques. RESULTS: The number of CD14(+) cells was
      stable during all phases of the menstrual cycle and early pregnancy. In
      comparison to nonpregnant endometrium, DC-SIGN(+) cells showed a higher
      proliferation rate and were found associated in clusters with CD56(+) natural
      killer (NK) cells in early pregnancy. In the late secretory phase of the
      menstrual cycle, numbers of CD83(+) (P <.01) cells were significantly higher than
      in other endometrial phases and early pregnancy. HLA-DR(+) expression was
      significantly increased in early pregnancy but remained unchanged throughout the
      menstrual cycle. CONCLUSION: The presence of DC-SIGN(+) cells during the
      menstrual cycle and their proliferation in early pregnancy suggests an important
      role of these cells with regard to the balance between defense against pathogens
      and tolerance of the fetal allograft. Whether the increase of CD83(+) mature DC
      and CD68(+) macrophages in the late secretory phase is caused by hormonal stimuli
      and/or is due to changes of the cytokine/chemokine micromilieu remains to be
      investigated.

PMID- 15458748
TI  - Immunomodulatory and transcriptional effects of progesterone through progesterone
      A and B receptors in Hec50co poorly differentiated endometrial cancer cells.
AB  - OBJECTIVE: Derivatives of progesterone, progestins, are used to treat endometrial
      cancer; however, the pathways activated by the hormone have not been fully
      investigated. Progesterone acts through two receptor isoforms, progesterone
      receptors A and B (PRA and PRB), transcription factors that control the
      expression of downstream genes leading to endometrial differentiation. The
      purpose of this study was to perform an expression analysis to identify the
      mechanisms underlying progesterone's growth suppressive and immunomodulatory
      effects in endometrial cancer. METHODS: To study the molecular effects of
      progesterone, PRs were introduced into Hec50co cells. Expression array analyses
      followed by confirmatory semiquantitive reverse-transcriptase polymerase chain
      reaction (RT-PCR) experiments were performed. RESULTS: Expression analysis
      demonstrated a significant effect of progesterone after 12 hours of treatment on
      a number of genes, including cell signaling, DNA remodeling, apoptotic, tumor
      suppressor, and transcription factors. Of particular interest was the consistent
      modulation of cytokines, which generally predicted for a powerful anti
      inflammatory effect of progesterone through PR. Specifically, pro-inflammatory
      genes such as TNFalpha, IL-1beta, and MCP-1/MCAF-1 were down-regulated and anti
      inflammatory genes such as TRAP1 and SMAD4 were induced. CONCLUSION: We have
      discovered that progesterone has a modulatory effect on inflammation and many
      other important cellular functions. These effects likely underlie the inhibitory
      effects of progesterone on tumor growth and invasion.

PMID- 15458749
TI  - Traditional systems of medicine.
AB  - Traditional ways of healing illnesses originating in ancient societies are called
      complementary medicine today. Many of the traditional medical systems are based
      on sound fundamental principles and centuries of practices by healers. This
      article reviews some of the most commonly practiced traditional medical systems.
      A common factor noted in several traditional systems is a holistic approach to
      the well-being of a person's body, mind, and spirit.

PMID- 15458750
TI  - The role of acupuncture in pain management.
AB  - This article reviews the theories and applications of acupuncture to
      musculoskeletal pain management. First, Chinese theories of acupuncture are
      discussed briefly. Next, current understanding of nociception and central pain
      modulation is discussed in detail,followed by discussion of the physiologic
      effect of acupuncture analgesia. Other theories of acupuncture analgesia are
      presented based on neuromodulation of the central nervous system. Finally,the
      efficacy of acupuncture for many musculoskeletal pain syndromes,including spine
      related pain, soft tissue pain, neuropathic pain, arthritis of the knee, and
      upper extremity tendinitis, is reviewed. The article concludes with a discussion
      of methodologic issues related to conducting randomized, placebo-controlled
      trials of acupuncture and goals for future research in this area of pain
      management.

PMID- 15458751
TI  - Tai Chi, Qi Gong and Reiki.
AB  - Tai Chi, Qi Gong, and Reiki are complementary therapies that are gaining
      popularity with patients. Although these therapies seem simple and attractive in
      their philosophy and are easy to apply,more objective, well-designed research is
      needed to prove their efficacy and to gain acceptance from the medical community.

PMID- 15458752
TI  - Yoga: a therapeutic approach.
AB  - Yoga, practiced widely in the East, is now popular in the West as part of a
      healthy lifestyle. This article brings a medical perspective to the practice of
      yoga. Selected yoga postures that are believed to benefit certain medical
      conditions are highlighted. In addition, the philosophy, general guidelines, and
      medical benefits of yoga practice are described.

PMID- 15458753
TI  - Rolfing.
AB  - Rolfing, or structural integration, is one of many types of manipulative therapy.
      This article describes the principles and history of Rolfing and reviews current
      research. Only a few clinical trials specifically have looked at Rolfing. Related
      research on deep tissue massage and myofascial release also is reviewed. Rolfing
      has a physiologic impact on the peripheral nervous system and on myofascial
      structures. Important clinical outcome measures, such as pain levels and
      function, have not been looked at specifically, however,in clinical trials.

PMID- 15458754
TI  - Alexander technique and Feldenkrais method: a critical overview.
AB  - This article develops an overall better understanding of the Alexander technique
      and Feldenkrais method. Initially, a brief history is provided to lay the
      groundwork for the development of these techniques. A description of the
      techniques, training requirements, and mechanism of action follows. Indications,
      contraindications, and patient selection are discussed. This article reviews and
      identifies what research has been completed and what areas need further
      investigation. Overall, the goal is to establish a guide to aid in determining
      who may benefit from these techniques and outcomes to expect when using these
      techniques.

PMID- 15458755
TI  - Art, dance, and music therapy.
AB  - Art, dance, and music therapy are a significant part of complementary medicine in
      the twenty-first century. These creative arts therapies contribute to all areas
      of health care and are present in treatments for most psychologic and physiologic
      illnesses. Although the current body of solid research is small compared with
      that of more traditional medical specialties, the arts therapies are now
      validating their research through more controlled experimental and descriptive
      studies. The arts therapies also contribute significantly to the humanization and
      comfort of modern health care institutions by relieving stress, anxiety, and pain
      of patients and caregivers. Arts therapies will greatly expand their role in the
      health care practices of this country in the twenty-first century.

PMID- 15458756
TI  - Hippotherapy.
AB  - Hippotherapy refers to the use of the movement of the horse asa treatment tool by
      physical therapists, occupational therapists,and speech-language therapists to
      address impairments, functional limitations, and disabilities in clients with
      neuromusculoskeletal dysfunction, such as cerebral palsy. Hippotherapy is used as
      part of an integrated treatment program to achieve functional outcomes.
      Hippotherapy engages the client in activities on the horse that are enjoyable and
      challenging. In the controlled hippotherapyenvironment, the therapist modifies
      the horse's movement and carefully grades sensory input, establishing a
      foundation for improved neurologic function and sensory processing. This
      foundation can be generalized to a wide range of daily activities,making the
      horse a valuable therapeutic tool for rehabilitation.

PMID- 15458757
TI  - Biopsychosocial pain medicine and mind-brain-body science.
AB  - This article reviews how emotions, behavior, and psychiatric comorbidity
      influence the course and outcome of chronic pain disorders and addresses methods
      of identifying and managing these problems in clinical practice. Successful
      medical rehabilitation for patients with chronic pain requires (1) appreciating
      the effects of biopsychosocial factors in the onset, course, and outcomes of pain
      disorders; (2) understanding neurobiologic mechanisms linking mind, brain, and
      body in the functions of pain perception and modulation; and (3) being able to
      review critically and use selectively the plethora of new medications and
      interventional technologies that are proposed in the literature. Deficits in
      these skills now are recognized as hazardous to the public health so that medical
      school education and post residency training in pain medicine is now mandatory in
      some states.

PMID- 15458758
TI  - Alternative cognitive therapy for emotional instability (pathologic laughing and
      crying).
AB  - Emotional instability (EI) is involuntary laughing and crying associated with
      brain damage seen in a variety of disorders. This article discusses occurrence,
      impact, and diagnosis, and neuroanatomic substrates underlying proposed
      mechanisms producing EI are outlined and related to traditional drug treatment.
      An expanded neuroanatomic model is suggested emphasizing the prefrontal cortex as
      the center integrating information from a complex emotion and sensory loop with
      motor information destined for the faciorespiratory nuclei in the brainstem.
      Disturbance at any level in the loop is proposed to produce EI by degrading
      information to or from the prefrontal cortex, disrupting its inhibitory control
      of the nuclei. An alternative cognitive therapy for EI was developed to
      compensate for deficits resulting from structural lesions by strengthening
      undamaged pathways, which is achieved by superimposing volitional movement on
      muscles affected during an EI episode. Treatment of 17 patients showed
      significant reductions in EI severity and occurrence, and in contrast to drug
      treatments,the effect was sustained at 3- to 6-month follow-up.

PMID- 15458759
TI  - Applied psychophysiology, clinical biofeedback, and rehabilitation
      neuropsychology: a case study--mild traumatic brain injury and post-traumatic
      stress disorder.
AB  - This article presents a case study of a 39-year-old European American married
      woman with a history of child and adolescent incest,marital rape, and physical
      abuse from her husband for more than 10 years. She was referred to a pain clinic
      for treatment of headaches and Tourette's syndrome. The client was evaluated with
      the Ackerman-Banks Neuropsychological Rehabilitation Battery to identify
      neuropsychological strengths and weaknesses. The Vulnerability to Stress Audit
      was used to identify life events that were positively and negatively influencing
      her life. The client was treated for mild traumatic brain injury, post-traumatic
      stress disorder,cognitive difficulties, impulsivity, confabulation, low
      frustration tolerance, and inability to evaluate and make decisions about
      socially appropriate behaviors. Treatment involved traditional psychotherapy,
      hypnosis, cognitive rehabilitation, biofeedback training, electromyography,
      finger temperature, and blood pressure.

PMID- 15458760
TI  - Complementary and alternative medicine education in the United States, China, and
      Taiwan.
AB  - As public demand for complementary and alternative medicine increases,it is
      important for physical medicine and rehabilitation physicians to have some basic
      understanding of complementary and alternative medicine or at least to appreciate
      some of the approved indications so that appropriate referrals can be made.
      Because the concept of evidence-based medicine is essential for a successful
      physical medicine and rehabilitation practice in either academic or private
      facilities, well-developed research projects, such as randomized, controlled
      trials of large sample size, are needed to investigate the efficacy and safety of
      complementary and alternative medicine therapy.

PMID- 15458761
TI  - Medical marijuana: emerging applications for the management of neurologic
      disorders.
AB  - Marijuana contains over 60 different types of cannabinoids, which are its
      medicinally active ingredients. Cannabinoids have the capacity for
      neuromodulation--through direct, receptor-based mechanisms--at many levels within
      the nervous system, providing therapeutic properties that may be applicable to
      the treatment of neurologic disorders. These include antioxidation,
      neuroprotection, analgesia, anti-inflammation, immunomodulation, modulation of
      glial cells, and tumor growth regulation. This article reviews the current and
      emerging research on the physiologic mechanisms of endogenous and exogenous
      cannabinoids and their applications in the management of neurologic disease.

PMID- 15458762
TI  - The demographics and economics of complementary alternative medicine.
AB  - Limitations of data in regard to complementary and alternative medicine (CAM)
      concern the tendency to lump types of CAM into broad areas and the lack of strong
      scientific evidence. Insurance benefit coverage is limited often to two or three
      types of CAM and is often consumer driven. Scientific evidence is used to justify
      noncoverage. Americans still are paying a large portion out-of pocket for CAM.
      Traditional medicine practitioners may find it difficult to recommend CAM
      treatments to patients given the cost,concern for quality control, side effects,
      and quality of scientific evidence.Regardless, consumers will continue to use
      CAM, particularly in chronic conditions, in which patients struggle to find any
      treatment that may cure their condition or improve their quality of life. Greater
      study of CAM is needed to determine efficacy, side effects, and cost
      effectiveness of appropriate CAM treatments to increase.

PMID- 15458763
TI  - Complementary and alternative medicine.

PMID- 15458764
TI  - Complementary and alternative medicine.

PMID- 15458765
TI  - Emerging aspects of pharmacotherapy for obesity and metabolic syndrome.
AB  - Obesity is a multifactorial, chronic disorder that has reached epidemic
      proportions in most industrialized countries and is threatening to become a
      global epidemic. Obese patients are at higher risk from coronary artery disease,
      hypertension, hyperlipidemia, diabetes mellitus, cancers, cerebrovascular
      accidents, osteoarthritis, restrictive pulmonary disease, and sleep apnoea. In
      particular, visceral fat accumulation is usually accompanied by insulin
      resistance or type 2 diabetes mellitus, hypertension, hypertriglyceridemia, high
      uremic acid levels, low high density lipoprotein (HDL) cholesterol to define a
      variously named syndrome or metabolic syndrome. Metabolic syndrome is now
      considered a major cardiovascular risk factor in a large percentage of population
      in worldwide. Both obesity and metabolic syndrome are particularly challenging
      clinical conditions to treat because of their complex pathophysiological basis.
      Indeed, body weight represents the integration of many biological and
      environmental components and relationships among fat and glucose tolerance or
      blood pressure are not completely understood. Efforts to develop innovative anti
      obesity drugs, with benefits for metabolic syndrome, have been recently
      intensified. In general two distinct strategies can be adopted: first, to reduce
      energy intake; second, to increase energy expenditure. Here we review some among
      the most promising avenues in these two fields of drug therapy of obesity and,
      consequently, of metabolic syndrome.

PMID- 15458766
TI  - Effect of urocortin on L-type calcium currents in adult rat ventricular myocytes.
AB  - The newly isolated peptide, urocortin (UCN) has been found to have potent
      cardioprotective effects. In order to investigate the effect of UCN on L-type
      calcium currents (I(Ca,L)), exploring the mechanisms of UCN's cardioprotective
      effects, we directly measured the I(Ca,L) in the adult rat cardiac myocytes
      exposed to UCN using standard whole-cell patch-clamp recording technique. Our
      results showed that UCN exerted decreasing effects on the I(Ca,L) of the single
      adult rat cardiac myocytes. The current density was inhibited by about 35% after
      exposure of the cells to UCN (0.1 micromol L(-1)) for 10 min, from the control
      value of 7.19 +/- 1.44 pA/pF to 4.74 +/- 0.75 pA/pF (n = 5, P < 0.05). This
      I(Ca,L)-inhibiting action of UCN was concentration dependent. Moreover, no
      frequency dependence of UCN effects on I(Ca,L) was observed. In combination with
      previous reports, our results suggest that there might be a close relationship
      between the cardioprotective effects of UCN and L-type calcium channels.

PMID- 15458767
TI  - Lippia alba, Melissa officinalis and Cymbopogon citratus: effects of the aqueous
      extracts on the isolated hearts of rats.
AB  - 1. This research was developed to evaluate the actions of the aqueous extracts of
      leaves of Lippia alba, Melissa officinalis and Cymbopogon citratus upon
      contractile force (CF) and cardiac rate (CR). 2. For the experiments in isolated
      heart, 21 male adult rats were used. The hearts were perfused according to
      Langendorff's method. The records of CF and CR were obtained in control and after
      application of the extracts. The extracts were utilized in doses: 0.038, 0.38,
      3.8 and 38 mg. Results obtained were compared by statistic analyses. 3. The
      aqueous extracts provoked significant CR reduction and did not alter the CF. The
      negative CR effect may have occurred by cardiac muscarinics receptors
      stimulation.

PMID- 15458768
TI  - A simple high-performance liquid chromatography assay for on-line determination
      of catecholamines in adrenal gland by direct injection on an ISRP column.
AB  - In the present research, assays were improved for the determination of
      catecholamines in adrenal gland. High-performance liquid chromatography with
      electrochemical detection was employed for quantitative analysis. The method
      involved direct injection of acid extract on to a serum albumin dimethylocadecyl
      silane (HSA-C18) and the utilization of phosphate buffer (pH = 3.0): methanol
      (97:3 v/v), 0.025 g heptanosulfonic acid and 0.0025 g EDTA as mobile phase. The
      detection was obtained using an electrochemical detector L-ECD-6A-Shimadzu with a
      potential of the 85 mV. Identification was based on retention time.
      Quantification was performed by automatic peak-area determination. The detection
      limit is equal to 0.5 ng ml(-1). The HPLC method with electrochemical detection
      proposed here permits good separation of catecholamines in samples of adrenal
      gland from rats. The method has various advantages: fast, high precision and good
      selectivity and do not require sample treatment. The immobilization stress during
      5 min did not provoke alteration in catecholamines contains in rat adrenal gland,
      due to the short time of the stress exposure. This study shows that the
      catecholamines (norepinephrine and epinephrine) adrenal increased significantly
      after the acute immobilization stress during 30 min as compared to control group.
      This increase probably is due to the emotional component of the immobilization
      stress. In conclusion, our studies suggest an effective participation of the
      adrenal glands to maintain the homeostasis of organism to the stressful
      conditions.

PMID- 15458769
TI  - The potential role of cyclooxygenase-2 inhibitors in the treatment of
      experimentally-induced mammary tumour: does celecoxib enhance the anti-tumour
      activity of doxorubicin?
AB  - The potential anti-tumour activity of non-steroidal anti-inflammatory drugs
      (NSAIDS) has been previously discussed. This study was undertaken to assess the
      possible anti-tumour activity of the cyclooxygenase-2 (COX-2) inhibitor;
      celecoxib in an animal model of mammary carcinoma; the solid Ehrlich carcinoma
      (SEC). The possibility that celecoxib may modulate the anti-tumour activity of
      doxorubicin on the SEC was also studied. Some of the possible mechanisms
      underlying such modulation were investigated. The anti-tumour activity of
      celecoxib (25 mg kg(-1)), diclofenac (12.5 mg kg(-1)) and doxorubicin (2 mg kg(
      1)) either alone or in combination were investigated on SEC in vivo through the
      assessment of tumour growth delay (TGD) and tumour volume (TV), changes in tumour
      DNA content and nitric oxide (NO) levels, immunohistochemical staining of the
      tumour suppressor gene product; p53 histopathological examination and
      determination of apoptotic index of SEC. In addition, the influence of these
      drugs on the DNA fragmentation pattern of Ehrlich carcinoma cells (ECC) was
      studied. It was found that both celecoxib and diclofenac lack the anti-tumour
      activity on SEC. In addition there was a significant increase in doxorubicin anti
      tumour activity when administered in combination with celecoxib. Moreover, it was
      found that both celecoxib and diclofenac have the potential to inhibit the
      function of P-glycoprotein (P-gp) in ECC using rhodamine uptake and efflux
      assays. Therefore, the current study suggested the chemosensitizing potential of
      celecoxib in the SEC animal model of mammary tumour, which could be explained in
      part on the basis of inhibition of P-gp function, with possible enhancement of
      doxorubicin anti-tumour activity.

PMID- 15458770
TI  - Effects of antiemetic drugs on glucose 6-phosphate dehydrogenase and some
      antioxidant enzymes.
AB  - The aim of this study was to investigate effect of antiemetics on G6PD and
      antioxidant enzymes. Antiemetics are currently being used to reduce or prevent
      nausea and vomiting in patients. This is the first study to show effect of
      antiemetics on glucose-6-phosphate dehydrogenase (G6PD) and antioxidant enzyme
      activities. For in vitro studies, G6PD was purified from human erythrocyte, 10,
      26-fold in a yield of 51.3% by using ammonium sulphate precipitation and 2',5'
      ADP-Sepharose 4B affinity gel. The purified enzyme showed a single band on sodium
      dodecyl sulfate-polyacrilamide gel electrophoresis (SDS-PAGE). The effects of
      four different antiemetics (granisetron hydrochloride, ondansetron hydrochloride,
      metoclopramide hydrochloride, trimethobenzamide hydrochloride) were investigated
      on the purified enzyme. Granisetron hydrochloride and ondansetron hydrochloride
      inhibited the enzyme activity (Ki values; 5.05 mM and 0.034 mM, I50 values; 3.9
      mM and 0.036 mM, respectively). Metoclopramide hydrochloride, trimethobenzamide
      hydrochloride showed no inhibition effects. In addition, in vivo studies, effects
      of ondansetron hydrochloride on the G6PD, glutathione reductase (GR), glutathione
      peroxidase (GPx) and catalase (CAT) were examined in the rat erythrocytes. G6PD
      (49% of control), GR (55% of control), CAT (60% of control) activities in
      erythrocytes were significantly decreased whereas GPx (183% of control) was
      significantly increased. A marked alteration in these enzymes may be result of
      oxidative stress in the rats receiving ondansetron hydrochloride.

PMID- 15458771
TI  - In vitro anti-tumor activity of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone
      against six established human cancer cell lines.
AB  - 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), isolated from the buds
      of Cleistocalyx operculatus, was investigated in its cytotoxicity and its
      influence on six human cancer cell lines. Among SMMC-7721, 8898, HeLa, SPC-A-1,
      95-D and GBC-SD cell lines, SMMC-7721 cells was the most sensitive one in these
      tested cell lines, with IC50 equal to 32.3 +/- 1.13 microM, EC50 equal to 9.00 +/
      0.36 microM and the therapeutic index equal to 3.59. Staining with Hoechst 33258
      showed fragmentation and condensation of chromatin in the cells treated with 9
      microM DMC for 48 h. Flow cytometric analysis was performed to determine
      hypodiploid cells. The results of flow cytometry assay indicated that the
      percentage of hypodiploid SMMC-7721 cells were 49.44 +/- 1.06% after 48 h
      treatment with 18.0 microM DMC. The treatment resulted in the appearance of a
      hypodiploid peak (A0 region), probably due to the presence of apoptosing cells
      and/or apoptotic bodies with DNA content less than 2n. To our knowledge, this is
      the first report on anti-tumor activity by DMC.

PMID- 15458772
TI  - Bioequivalence evaluation of two marketed brands of stavudine 40 mg capsules in
      healthy human South African volunteers.
AB  - Stavudine (d4T), a thymidine nucleoside analogue has been effectively used for
      treatment of patients infected with HIV. A randomized, two-way, crossover study
      was conducted in 24 fasting, healthy, Caucasian male volunteers to compare plasma
      pharmacokinetic (PK) profile and single-dose tolerability of a new d4T
      formulation (Stavir, Cipla Ltd, India; 40 mg capsule, test, T) with that of
      reference (R) formulation (Zerit), Bristol-Myers Squib, NJ, USA; capsule, 40 mg).
      Each volunteer received T and R formulation separated by at least 10 days of drug
      free wash-out period. Plasma concentrations of d4T, determined upto 24h post-dose
      by a validated LC-MS/MS assay were utilized to assess PK parameters such as
      maximum observed plasma concentration (Cmax), time to Cmax (tmax), and area under
      plasma concentration curve (AUC(infinity)). The primary plasma PK parameters,
      Cmax, and AUC(infinity), of anti-retroviral were comparable for either of the
      formulations. tmax was achieved within an hour suggesting rapid absorption of d4T
      from both formulations. Geometric mean ratios (GMR) (percentage reference) of
      AUC(infinity) and Cmax, and their 90% confidence intervals (CI) were 106.32
      [102.52-110.26] and 102.32 [90.25-116.00], respectively. As the 90% CI of GMR
      were entirely within 80-125% for log-transformed parameters, two formulations
      were considered bioequivalent, in the extent and rate of absorption. Both
      formulations exhibited similar tolerability under fasting conditions.

PMID- 15458773
TI  - Effects of sibutramine on anxiety-related behaviours in rats.
AB  - Sibutramine is an anorexiant drug that inhibits the reuptake of noradrenaline and
      serotonin, a pharmacological property shared with drugs clinically effective in
      treating anxiety pathologies. However, the effects of this compound on
      experimental and clinical anxiety have not been assessed yet. In this study, we
      evaluated the effects of sibutramine on anxiety-related behaviours which have
      been related to specific anxiety disorders. Acute injection of sibutramine (5, 10
      or 20 mg kg(-1); intraperitoneally) in male Wistar rats impaired inhibitory
      avoidance in the elevated T-maze (ETM) and in the light/dark transition test,
      indicative of an anxiolytic effect. The drug also inhibited one-way escape in the
      ETM. Sibutramine, however, was ineffective in changing rat performance in the
      elevated plus-maze. Therefore, sibutramine decreased the expression of defensive
      behaviours that have been associated with generalized anxiety disorder
      (inhibitory avoidance) and with panic disorder (one-way escape). Yet, in contrast
      to what has been reported with drugs such as the tricyclic anti-depressants that
      also inhibit monoamine reuptake, the anxiolytic effects of sibutramine were
      revealed after a single administration.

PMID- 15458774
TI  - Effects of N-acetylcysteine on arginase, ornithine and nitric oxide in renal
      ischemia-reperfusion injury.
AB  - BACKGROUND: Renal ischemia-reperfusion (I/R) is a complex syndrome involving
      several mechanisms such as renal vasoconstrictions, extensive tubular damage and
      glomerular injury. N-Acetylcysteine (NAC), a potent antioxidant by itself, may
      serve as a precursor for glutathione synthesis. The aim of this study was to
      investigate the possible effects of NAC on liver and kidney tissue arginase
      activity, ornithine and plasma nitric oxide levels during the I/R injury of
      kidney. METHODS: Twenty-four female Sprague-Dawley rats divided into three
      groups: group 1; was given saline intraperitoneally (i.p.). Saline to group 2 and
      NAC (300 mg kg(-1)) to group 3 were injected i.p. 30 min before induction of
      ischemia. Groups 2 and 3; subjected to bilateral renal ischemia (60 min) followed
      by reperfusion (24 h). After the reperfusion period, the rats were sacrificed and
      liver and kidney tissue arginase activities, ornithine and plasma nitric oxide
      (NO) levels were determined. RESULTS: NAC had an increasing effect on both of
      liver and kidney tissue arginase activities and ornithine levels while decreasing
      plasma NO concentration. CONCLUSION: The stimulatory effect of NAC on arginase
      activity may result in an inhibition of the plasma NO level. Moreover, it could
      be possible that one of the protective mechanisms of NAC might be through the
      stimulation on the both liver and kidney tissue ornithine levels.

PMID- 15458775
TI  - Effect of the exogenous glutamate and the NMDA on electric field-stimulated
      contractions of isolated rat ileum.
AB  - While neurotransmitter role of glutamate in gastrointestinal intrinsic nervous
      system was shown, its effects in various segments of gastrointestinal tract were
      not yet understood completely. In our study, we have investigated effects of
      exogenous glutamate on electric field-stimulated contractions of isolated rat
      ileum. The ilea from forty Wistar rats of both sexes were isolated in an organ
      bath, according to the Magnus mounting method, and exposed to field stimulation
      with square wave pulses (20 V over the electrodes, 400 mA, 1 ms duration,
      frequency 16 Hz, pulse trains for 30 s with 30 s pause). The stimulation produced
      tonic contractions and relaxations recorded with an isometric system. Atropine
      (2.3 x 10(-6) M/l) completely abolished contractions of isolated rat ileum
      produced by the field stimulation, while relaxations remained unaffected.
      Glutamate (from 7.8 x 10(-6) to 3.5 x 10(-3) M/l) and N-Methyl-D-aspartic acid
      (NMDA) (from 9.1 x 10(-9) to 1.3 x 10(-5) M/l) caused concentration-dependent
      inhibition of the field-stimulated contractions of isolated rat ileum (EC50 was
      90.17 +/- 1.81 x 10(-5) and 53.51 +/- 3.68 x 10(-9) M/l, respectively) while not
      affecting the field-stimulated relaxations. On the other hand, (RS)-alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (from 6.0 x 10(-9) to 9.3 x 10(
      6) M/l), kainic acid (from 5.8 x 10(-9) to 8.3 x 10(-6) M/l) and (+/-)-1
      aminocyclopentane-trans-1,3-dicarboxylic acid ((+/-)-trans-ACPD) (from 7.0 x 10(
      9) to 1.1 x 10(-5) M/l) did not influence both the field-stimulated contractions
      and the field-stimulated relaxations of isolated rat ileum. The results of our
      study suggest inhibitory effect of glutamate on acetylcholine release from
      intrinsic neurons of rat ileum, mediated through NMDA receptors.

PMID- 15458776
TI  - Gastrointestinal and hepatic toxicity of selective and non-selective
      cyclooxygenase-2 inhibitors in pregnant and non-pregnant rats.
AB  - The aim of the study was to evaluate the toxicity of non-selective (tolmetin,
      ibuprofen and piroxicam) and selective (DFU) cyclooxygenase-2 inhibitors on
      pregnant and non-pregnant rats. The drugs were administered orally once (DFU,
      piroxicam) or three times (tolmetin, ibuprofen) a day from days 8 through 21 of
      gestation experiment in three doses. The initial dose was similar to the human
      antiinflammatory one and set as 8.5 mg/kg (tolmetin, ibuprofen), 0.3 mg/kg
      (piroxicam) and 0.2 mg/kg (DFU). The middle dose was increased 10 times and the
      highest one 100 times the initial dose. The highest dose for ibuprofen was set at
      200mg/kg due to high mortality. On gestation/experimental day 21 animals were
      sacrificed, blood was collected and abdominal organs were taken for pathological
      examination. Activity of alanine and asparate aminotransferases and levels of
      total protein and urea were determined. Stomach, small and large intestines, and
      liver were grossly and histologically examined. Dose-dependent mortality, signs
      of gastrointestinal toxicity, and significant changes of biochemical parameters
      were found in groups exposed to non-selective COX inhibitors in both pregnant and
      non-pregnant rats. Mild regressive structural hepatic changes were observed.
      Significant decrease of protein level in non-pregnant rats treated with high DFU
      dose, and occasionally observed gastrointestinal changes were the only changes
      noted in groups exposed to the selective COX-2 inhibitor. Tolerability of non
      selective COX inhibitors was lower in both pregnant and non-pregnant groups when
      compared with DFU. Insignificant mortality and histological changes were noted
      between pregnant and non-pregnant groups.

PMID- 15458777
TI  - The use of a model of in vivo macrophage depletion to study the role of
      macrophages during infection with Bacillus anthracis spores.
AB  - The pathogenesis of infection by Bacillus anthracis has been the subject of many
      investigations, but remains incompletely understood. It has been shown that B.
      anthracis spores germinate in macrophages and perhaps require this intracellular
      niche to germinate in vivo before outgrowth of the vegetative organism. However,
      it has also been reported that macrophages are sporicidal in vitro. In our in
      vivo model, macrophages were depleted from mice by either silica treatment or
      treatment with liposome-encapsulated dichloromethylene disphosphonate (Cl(2)MDP),
      and the animals were infected parenterally with virulent ungerminated B.
      anthracis (Ames strain) spores. The mice in which macrophages had been depleted
      were killed more rapidly than untreated mice. In addition, augmenting peritoneal
      populations of macrophages with cultured RAW264.7 cells partially protected mice
      from disease, increasing the survival rate in a dose dependent relationship.
      Alveolar macrophages were depleted by intranasal instillation of liposome
      encapsulated Cl(2)MDP. The animals with normal alveolar macrophage numbers had
      significantly greater survival rates after inhaling B. anthracis spores than the
      macrophage-depleted mice. These findings do not preclude the observations that
      macrophages provide a site permissive for spore germination, however, these data
      suggest that macrophages do play an important role in limiting and/or clearing a
      B. anthracis infection.

PMID- 15458778
TI  - Stat 4 but not Stat 6 mediated immune mechanisms are essential in protection
      against plague.
AB  - The Caf1 and LcrV sub-unit vaccine for plague has been shown to be highly
      protective against challenge with virulent Yersinia pestis in a mouse model.
      Production of large amounts of IgG1 in response to the vaccine correlates with
      protection against aerosol and parenteral infection. In this study the effect of
      genetic mutation in the immune system on protection was addressed. Stat 6(-/-)
      mice which are unable to utilise the type 2 cytokines IL-4 and IL-13 and so
      should have reduced IgG1 responses were utilised in order to determine whether an
      immune system biased towards the type 1 axis could mount an effective response to
      the vaccine. Conversely in the Stat 4(-/-) mouse model, IL-12 and interferon
      gamma-mediated immune mechanisms are inactive and the immune response should be
      biased towards the type 2 axis. Serum antibody responses to vaccination in both
      the knockout strains and their wild type controls revealed little difference in
      levels of IgG and isotype profiles. Elispot analysis of cytokine production at
      the single cell level did however reveal a functional defect in the Stat 4(-/-)
      mice which had low levels of IFN-gamma producing cells. Following virulent
      challenge, the Stat 6(-/-) mice showed high levels of protection, while the Stat
      4(-/-) mice were poorly protected, indicating a fundamental defect in their
      immune systems which could not be overcome even by the passive transfer of CD4(+)
      cells from immunised BALB/c donors. It appears therefore that type 1 immune
      mechanisms, activated following Stat 4 phosphorylation, are essential in
      protection against plague.

PMID- 15458779
TI  - Toll-like receptor 4 (TLR4) does not confer a resistance advantage on mice
      against low-dose aerosol infection with virulent type A Francisella tularensis.
AB  - Francisella tularensis, the causative agent of tularemia, is a gram-negative
      facultative intracellular bacterium. Toll-like receptor (TLR) 4 is considered to
      be critical for inducing host innate immunity against many gram-negative bacteria
      including many respiratory pathogens. To determine the role of TLR4 in host
      defense against airborne F. tularensis infection, TLR4-defective C3H/HeJ
      (TLR4(d)) or wild-type C3H/HeOuJ (WT) mice were challenged by low-dose aerosol
      with type A F. tularensis, and the course of the infection and host responses
      were compared at day 2 and 4 post-inoculation (dpi). At dpi 2, bacterial burdens
      in the lungs were similar between TLR4(d) and WT mice, but TLR4(d) mice
      surprisingly harbored approximately 10-fold fewer bacteria in their spleens and
      livers. However, the bacterial burdens at dpi 4, the mortality and median time to
      irreversible moribundity were indistinguishable between the two mouse strains. In
      addition, the inflammatory responses to the infection, as reflected by the
      cytokine levels and leukocyte influx in the bronchoalveolar lavage fluid and
      histopathological analysis, were similar between both mouse strains.
      Additionally, as with C3H mice, we found no difference in either the median time
      to death or the survival rate between TLR4-deleted C57BL/10ScNJ mice and WT
      C57BL/10 mice. Combined, these data suggest that TLR4 does not contribute to
      resistance of mice to airborne type A F. tularensis infection.

PMID- 15458780
TI  - Alteration of gene expression in human middle ear epithelial cells induced by
      influenza A virus and its implication for the pathogenesis of otitis media.
AB  - Influenza A virus infection plays a significant role in the pathogenesis of
      Streptococcus pneumoniae-induced acute otitis media in children. An understanding
      of how influenza A virus modulates host cellular responses is critically
      important in efforts to explore the molecular mechanisms of this synergism. We
      used microarray technology to characterize the mRNA expression profile in human
      middle ear epithelial cells induced by influenza A virus. Alterations of mRNA
      expression in 142 out of approximately 12,600 genes were observed at 24h after
      virus infection. Of these 142 genes with altered expression, interferon inducible
      genes, chemokine and cytokine genes, pro- and antiapoptotic genes, signal
      transduction and transcription factors, cellular immune response, cell cycle and
      metabolism genes were the most prominent. Our results reveal several previously
      unknown alterations of host gene expression induced by influenza A virus which
      may provide new targets for further analysis of its role in this particular host
      pathogen interaction.

PMID- 15458781
TI  - Identification of Francisella tularensis genes encoding exported membrane
      associated proteins using TnphoA mutagenesis of a genomic library.
AB  - Francisella tularensis, the causative agent of tularemia, is a highly infectious
      pathogen of humans and animals, yet little is known about the surface proteins of
      this organism that mediate mechanisms of pathogenicity. lambdaTnphoA was used to
      generate random alkaline phosphatase gene fusions in a F. tularensis subsp.
      tularensis (strain Schu S4) genomic library to identify genes encoding exported
      extracytoplasmic proteins. Eleven genes encoding membrane-associated proteins
      were identified by this method and their respective signal peptides were
      characterized. Three of the genes encoded conserved 'housekeeping' enzymes, while
      the other eight genes were unique to F. tularensis, encoding proteins with
      molecular masses ranging from 11 to 78kDa as deduced from the amino acid
      sequences. Two genes putatively encoded lipoproteins based on the presence of
      characteristic signal peptidase II cleavage sites. Four selected proteins were
      found associated with outer membranes from Schu S4 and LVS strains by Western
      blotting. Indirect immunofluorescence of strain Schu S4 cells also showed
      evidence of protein localization to the outer membrane. Protein database searches
      produced significant alignments with proteins from other bacteria involved in
      carbohydrate transport, lipid metabolism, and cell envelope biogenesis, thereby
      providing clues for putative functions. These findings demonstrated that TnphoA
      mutagenesis can be used in conjunction with F. tularensis genome sequence data to
      provide a foundation for studies to identify and define cellular surface protein
      virulence factors of this pathogen.

PMID- 15458782
TI  - Sequential patterns of gene expression by bovine monocyte-derived macrophages
      associated with ingestion of mycobacterial organisms.
AB  - We investigated mechanisms involved in killing of mycobacterial organisms by
      comparing the response of bovine monocyte-derived macrophages to ingestion of
      Mycobacterium avium subsp. paratuberculosis or M. avium subsp. avium organisms.
      Previous studies have shown that bovine macrophages have the capacity to kill M.
      avium subsp. avium organisms in vitro but cannot kill M. avium subsp.
      paratuberculosis organisms. We used bovine cDNA microarray technology to
      investigate sequential gene expression by bovine monocyte-derived macrophages and
      function assays to correlate gene expression with biological activity. Results of
      the gene expression studies indicated substantial differences between macrophages
      phagocytizing the two organisms. At 2, 6, and 24h after infection, 12, 53, and 19
      genes, respectively, were differentially expressed. Over all time periods,
      approximately twice as many genes had lower expression in M. avium subsp.
      paratuberculosis-infected macrophages than had greater expression. Differentially
      regulated genes of most interest to antimicrobial responses included inflammatory
      molecules (transforming growth factor-beta, thrombospondin 1, monocyte chemokine,
      and cathepsin K), phagosome-lysosome-related genes (H(+) ATPases, lysosomal
      associated membrane protein 2, vesicle trafficking protein, and solute carrier
      protein), and apoptosis-related genes (tumor necrosis factor receptor-associated
      factor 2, and tumor protein p(53) binding protein). Function assays indicated
      that M. avium subsp. avium-infected macrophages had a greater capacity to acidify
      phagosomes and a greater percentage of apoptotic cells. In conclusion, these
      results suggest that a complex interaction between macrophages and mycobacterial
      organisms is involved in determining the fate of the organism. Although multiple
      genes and metabolic pathways are involved, the capacity of cells to acidify
      phagosomes and induce apoptosis appears to play a prominent role.

PMID- 15458783
TI  - Multi-organic risk assessment--summary of a CREDO cluster workshop.

PMID- 15458784
TI  - Endocrine disruptors and human health: is there a problem.
AB  - It has been hypothesized that endocrine-active chemicals (EACs) may be
      responsible for the increased incidence of breast cancer and disorders of the
      male reproductive tract. Synthetic chemicals with estrogenic activity
      (xenoestrogen) and the organochlorine environmental contaminants polychlorinated
      biphenyls (PCBs) and DDE have been the prime etiologic suspects. However, results
      of extensive research on PCBs and DDE does not show a correlation between PCB/DDE
      exposure and development of breast cancer. Studies also show that sperm count
      levels vary with demography, and the hypothesized coordinate global decrease in
      sperm counts and other disorders of the male reproductive tract is not supported
      by published data. In contrast, testicular cancer is increasing in most
      countries, and causal environmental/lifestyle factors for this disease are
      unknown.

PMID- 15458785
TI  - Integrated risk assessment and endocrine disrupters.
AB  - 1. The procedures currently employed for risk assessment are unlikely to be
      sustainable in the future for a variety of reasons. A number of actions are
      needed to remedy the situation and the most important of these actions are: * to
      improve access to existing data; * to introduce a prioritisation system based on
      exposure assessment; * to co-ordinate and harmonise approaches of different
      organisations involved in risk assessment. 2. Integration of information and
      methodologies between human health risk assessment and ecological risk assessment
      (integrated risk assessment) is advocated in this paper as one of the most
      important steps towards a holistic and effective way of conducting a risk
      assessment. 3. A framework is proposed for identification of agents for which an
      integrated risk assessment would be of particular value. Close collaboration
      across disciplines and across countries is necessary for the potential of
      integrated risk assessment to be realised in practice. The practicality of
      applying integrated risk assessment to endocrine disrupting agents is presently
      being investigated in an EU funded multi-laboratory collaborative study (CREDO).

PMID- 15458786
TI  - OECD test strategies and methods for endocrine disruptors.
AB  - The question whether (man-made or natural) chemical substances may have an
      adverse effect on the endocrine system has gained high visibility in the public
      as well as in the scientific community. This relates to possible effects on the
      environment as well as on human health for chemicals with (anti)estrogenic,
      (anti)androgenic or (anti)thyroid activity. Taking into account the broad
      universe of chemicals to which humans or the environment may be exposed, a sound
      testing strategy and robust test methods are urgently needed. Both subjects have
      been addressed by a specific OECD working group (EDTA-Endocrine Disruptor Testing
      and Assessment Task Force) involving regulatory agencies, the scientific
      community, chemical industry and NGOs. Like other organizations the OECD has
      adopted a tiered-testing strategy with the first tier using screening assays as
      quick and inexpensive tools, providing a way of generating alerts to potential
      endocrine activity that can be used to prioritize substances for definitive tests
      that then can determine the toxicological consequences of endocrine toxicity. The
      efforts of the OECD have therefore concentrated on the validation of specific
      screening and testing guidelines, like the uterotrophic, the Hershberger, and the
      "enhanced TG 407" test. The experimental testing necessary for this validation
      procedure is completed for the uterotrophic and the "enhanced TG 407" tests and
      near completion for the Hershberger assay. The data obtained so far have been
      published (for the uterotrophic assay) or will be submitted to the EDTA working
      group for final evaluation. Overall, the validation program has been very
      successful and should be sufficient for setting up OECD test guidelines for these
      experimental procedures. This will add substantially to the "tool-box" of OECD
      test methods that is available internationally to regulatory agencies and
      chemical industry for the identification and assessment of possible endocrine
      disruptors. Despite this success it is well recognized that the methodological
      "tool-box" should be supplemented by further screening and testing procedures
      related to effects on human health and the environment.

PMID- 15458787
TI  - Comparative toxicological pathology in mammals and fish: some examples with
      endocrine disrupters.
AB  - Toxicologic pathology is a classical discipline in the toxicology arena, and
      despite various emerging techniques, still is a major cornerstone in the process
      of hazard identification and risk characterization. Most knowledge derives from
      laboratory animal studies and, to a lesser extent, human data. Currently interest
      is growing in applying toxicological pathology for lower animals, in particular
      fish as being the most developed aquatic genus. This is triggered by the interest
      in so-called endocrine disrupting chemicals (endocrine disrupters, EDCs),
      xenobiotics that interfere with the endocrine system and thus may affect
      reproduction and/or development, and for which pathology is an essential
      technique in general in vivo studies. As the aquatic ecosystem is a major
      recipient of pollutants, fish constitute an important potential target and can be
      used as a research and bio-monitoring tool. For this goal knowledge of the
      pathological responses of fish to EDCs is essential and therefore we have studied
      the responses of laboratory fish to a set of reference endocrine modulating
      chemicals. In this paper, such effects are compared with known response patterns
      in mammals, thereby accounting for the specific aspects of anatomy and physiology
      in fish.

PMID- 15458788
TI  - Are all EDC effects mediated via steroid hormone receptors?
AB  - Despite the surge of interest in the endocrine disruption field, there is still
      no globally accepted definition of the term. There is a great political will to
      test chemicals to determine whether they have endocrine disrupting potential.
      This is a huge task and the US Environmental Protection Agency has taken the lead
      by setting up an Endocrine Disruptor Screening and Testing Advisory Committee
      (EDSTAC), which with international co-operation, will ultimately deliver a
      validated testing strategy to detect endocrine disrupting chemicals (EDCs) in
      humans and wildlife. One of the major developments will be the use of high
      throughput pre-screening (HTPS) methods that will detect binding to steroid
      receptor hormones, although many other testing methods will be employed. This
      paper describes two mechanisms of EDC action that are not mediated via steroid
      receptors; firstly, the suppression of fetal testosterone synthesis in rodents by
      in utero exposure to phthalates; and secondly, the ability of several chemicals
      to interfere with steroid metabolism by inhibiting estrogen sulfotransferases.
      These examples will be discussed with reference to pertinent human disorders,
      which have been associated with exposure to EDCs. Issues and questions about how
      scientists and regulators can deal with these types of chemicals or potential
      mechanisms in a risk assessment paradigm are raised.

PMID- 15458789
TI  - In silico tools to aid risk assessment of endocrine disrupting chemicals.
AB  - In silico or computational tools could be used more effectively in endocrine
      disruptor risk assessment for prescreening potential endocrine disruptors,
      improving experimental in vitro screening assay design and facilitating more
      thorough data analyses. The in silico tools reviewed here are three-fold and
      include the use of: (1) nuclear receptor (NR) crystal structures and homology
      models to examine potential modes of ligand binding by different representative
      compounds; (2) multivariate principal component analyses (PCA) techniques to
      select best predicted cell lines for endocrine disrupting chemicals (EDC) risk
      assessment purposes; (3) NR quantitative structure-activity relationships (QSARs)
      that can be constructed from varied biological data sources, using multivariate
      partial least squares (PLS) techniques and specific descriptors. The cytosolic
      and NR examples discussed here include the Ah receptor, (AhR), the human
      oestrogen receptor alpha (hERalpha) and the human pregnane X receptor (PXR). The
      varied biological data sets can be compared to give a more integrated dimension
      to receptor cross talk mechanisms, with further support from molecular modelling
      studies.

PMID- 15458790
TI  - Estrogen receptor-alpha mediates the detrimental effects of neonatal
      diethylstilbestrol (DES) exposure in the murine reproductive tract.
AB  - It is generally believed that estrogen receptor-dependent and -independent
      pathways are involved in mediating the developmental effects of the synthetic
      estrogen, diethylstilbestrol (DES). However, the precise role and extent to which
      each pathway contributes to the resulting pathologies remains unknown. We have
      employed the estrogen receptor knockout (ERKO) mice, which lack either estrogen
      receptor-alpha (alphaERKO or estrogen receptor-beta (betaERKO), to gain insight
      into the contribution of each ER-dependent pathway in mediating the effects of
      neonatal DES exposure in the female and male reproductive tract tissues of the
      mouse. Estrogen receptor-alpha female mice exhibited complete resistance to the
      chronic effects of neonatal DES exposure that were obvious in exposed wild-type
      animals, including atrophy and epithelial squamous metaplasia in the uterus;
      proliferative lesions of the oviduct; and persistent cornification of the vaginal
      epithelium. DES-mediated reduction in uterine Hoxa10, Hoxa11 and Wnt7a expression
      that occurs wild-type females during the time of exposure was also absent in
      alphaERKO females. In the male, alphaERKO mice exhibited complete resistance to
      the chronic effects of neonatal DES exposure on the prostate, including decreased
      androgen receptor levels, epithelial hyperplasia, and increased basal cell
      proliferation. Although ERbeta is highly expressed in the prostate epithelium,
      DES-exposed betaERKO males exhibited all of the effects of neonatal DES exposure
      that were observed in similarly exposed wild-type males. Therefore, the lack of
      DES-effects on gene expression and tissue differentiation in the alphaERKO uterus
      and prostate provides unequivocal evidence of an obligatory role for ERalpha in
      mediating the detrimental actions of neonatal DES exposure in the murine
      reproductive tract.

PMID- 15458791
TI  - Whole body action of xenoestrogens with different chemical structures in estrogen
      reporter male mice.
AB  - The present work tested the estrogenic activity of three weak environmental
      estrogens p,p'DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane], p,p'DDE [1,1
      dichloro-2,2-bis(p-chlorophenyl)ethylene] and betaBHC [beta-benzene-hexachloride]
      in the transgenic estrogen-reporter mouse model (ERE-tK-LUC). By a time dependent
      analysis of the transgenic reporter expression (luciferase), we showed that all
      these chemicals modulated the estrogen receptors (ERs) in the whole body,
      although with a different efficacy and depending upon the tissue analyzed. Peak
      activity was registered at 16 h of treatment with 5000 microg/kg of each
      compound. Organochlorines are lipophylic molecules that accumulate in fat. During
      weight loss they are mobilized and their concentration increases in blood. We
      tested whether after experimental accumulation in fat tissue, followed by a 48 h
      period of fasting, these compounds could be modulated to reach sufficient levels
      to activate the ERs in target tissues. This experimental setting produced results
      that were different from those obtained following acute treatments. In loaded
      mice, fasting induced betaBHC mobilization resulted in strong ER activation in
      the liver, lung, eye, cerebellum, hypothalamus and cortex. p,p'DDT mobilization
      had no effect in these tissues, but efficiently acted in the testis, where, on
      the contrary, betaBHC inhibited reporter expression. During fasting, betaBHC,
      p,p'DDT and the metabolite p,p'DDE increased in blood concentration, from 2.7 +/-
      0.36, 0.65 +/- 0.01 and 0.48 +/- 0.06 microg/ml to 9.51 +/- 1.1, 4.98 +/- 0.77
      and 6.0 +/- 0.71 microg/ml, respectively. We conclude that these organochlorines
      modulate differently the expression of estrogen regulated genes in a tissue- and
      compound-specific manner and that their action is dependent on the energy
      balance. Moreover, we show that this mouse model is suitable to detect the
      estrogenic activity of chemicals with variable structures such as alkyl phenols
      and polychlorobiphenyls.

PMID- 15458792
TI  - Impact of androgenic/antiandrogenic compounds (AAC) on human sex steroid
      metabolizing key enzymes.
AB  - Various pesticides, industrial pollutants and synthetic compounds, to which human
      populations are exposed, are known or suspected to interfere with endogenous sex
      hormone functions. Such interference potentially affect the development and
      expression of the male and female reproductive system or both. Chemicals in this
      class are thus referred to as endocrine disruptors (ED). This emphazises on the
      relevance of screening ED for a wide range of sex hormone-mimicking effects.
      These compounds are believed to exert influence on hormonal actions predominantly
      by (i) interfering with endogenous steroids in that they functionally interact
      with plasma membrane-located receptors as well as with nuclear receptors both for
      estrogens and androgens or (ii) affecting the levels of sex hormones as a result
      of their impact on steroid metabolizing key enzymes. Essential sex hormone
      related enzymes within the endocrine system of humans are aromatase, 5alpha
      reductase 2 as well as specific sulfotransferases and sulfatases (so-called phase
      I and phase II enzymes, respectively). Using suitable human tissues and human
      cancer cell lines (placenta, prostate, liver and JEG-3, lymph node carcinoma of
      prostate (LnCaP) cells) we investigated the impact of 10 widely used chemicals
      suspected of acting as ED with androgenic or antiandrogenic activity (so-called
      AAC) on the activity of these sex hormone metabolizing key enzymes in humans. In
      addition, the respective effects of six substances were also studied as positive
      controls due to their well-known specific hormonal agonistic/antagonistic
      activities. The aim of this report and subsequent investigations is to improve
      human health risk assessment for AAC and other ED.

PMID- 15458793
TI  - Multi-organic endocrine disrupting activity of the UV screen benzophenone 2 (BP2)
      in ovariectomized adult rats after 5 days treatment.
AB  - The chemical industry has developed sun protection factor products, which contain
      a variety of so-called "UV screens", among others, benzophenones (BP). Based on
      the structure it can be assumed, that the variant BP2 may be a potent estrogenic
      endocrine disrupter (ED). Only very limited data are available in the literature
      about such action of BP2, which focussed on the uterotrophic effect in immature
      rats. However, determination of ED activity in the uterus is only a restricted
      approach with the potential risk of missing undesirable actions. Therefore, we
      examined a putative multiple organ ED activity of BP2 by measuring gene
      expression of marker genes in the uterus, liver, vagina and pituitary after 5
      days oral application in adult ovariectomized (ovx) rats. An effect on lipid
      metabolism was assessed by determination of cholesterol, high- and low-density
      lipoproteins (HDL and LDL) in the blood. As control compound, estradiol (E2) was
      included in the study. A dose dependent E2-agonistic activity was observed in the
      uterus (increased weight), vagina (increased IGF1 expression), pituitary (reduced
      LH synthesis), liver (increased IGF1 expression) and lipid parameters
      (reduction). A non-E2-like action of BP2 was observed on T4- and T3-levels, which
      were significantly reduced. Except for the action of BP2 on thyroid hormone
      levels where it may inhibit thyroid peroxidase, this UV screen exerts clear E2
      agonistic actions. Application of BP2 for 5 days proved to be a sufficient
      treatment period to unravel a multi-organic endocrine disrupting activity of this
      UV screen.

PMID- 15458794
TI  - Endocrine active compounds affect thyrotropin and thyroid hormone levels in serum
      as well as endpoints of thyroid hormone action in liver, heart and kidney.
AB  - To assess interference with endocrine regulation of the thyroid axis, rats
      (female, ovariectomised) were treated for 12 weeks with the suspected endocrine
      active compounds (EAC) or endocrine disrupters (ED) 4-nonylphenol (NP), octyl
      methoxycinnamate (OMC) and 4-methylbenzylidene-camphor (4-MBC) as well as 17beta
      estradiol (E2) and 5alpha-androstane-3beta,17beta-diol (Adiol) on the background
      of a soy-free or soy-containing diet, and endpoints relevant for regulation via
      the thyroid axis were measured. Thyrotropin (TSH) and thyroid hormone (T4, T3)
      serum levels were altered, but not in a way consistent with known mechanisms of
      feedback regulation of the thyroid axis. In the liver, malic enzyme (ME) activity
      was significantly increased by E2 and Adiol, slightly by OMC and MBC and
      decreased by soy, whereas type I 5'-deiodinase (5'DI) was decreased by all
      treatments. This may be due rather to the estrogenic effect of the ED, as there
      is no obvious correlation with T4 or T3 serum levels. None of the substances
      inhibited thyroid peroxidase (TPO) in vitro, except for NP. In general, several
      endocrine active compounds disrupt the endocrine feedback regulation of the
      thyroid axis. However, there was no uniform, obvious pattern in the effects of
      those ED tested, but each compound elicited its own spectrum of alterations,
      arguing for multiple targets of interference with the complex network of thyroid
      hormone action and metabolism.

PMID- 15458795
TI  - Pure estrogenic effect of benzophenone-2 (BP2) but not of bisphenol A (BPA) and
      dibutylphtalate (DBP) in uterus, vagina and bone.
AB  - Contradictory results whether the endocrine disrupters (ED) benzophenone-2 (BP2),
      bisphenol A (BPA) and dibutylphtalate (DBP) exert estrogenic effects have been
      published. Selective estrogen receptor modulators (SERMs) exert estrogenic
      effects in some but not in all organs and ED may be SERMs. Therefore, we studied
      their binding properties to recombinant ERalpha and ERbeta protein and their
      effects in the uterus, vagina and bone of ovariectomized rats. BP2 bound to both
      receptor subtypes, while BPA had a relatively high ERbeta selectivity. DBP did
      not bind to ERalpha but with a low affinity to ERbeta. In the uterus, only E2 and
      BP2 increased uterine weight and the complement C3 but decreased ERbeta gene
      expression. Discrete effects of BPA and DBP in the uterus were found upon
      histological examination. In the vagina, BP2 but not BPA and DBP had clear
      estrogenic effects. E2 and BP2 had antiosteoporotic effects in the metaphysis of
      the tibia. The serum surrogate parameters of bone metabolism, i.e. osteocalcin
      and the cross (rat) laps were significantly reduced by E2, an effect shared with
      BP2 but not by the two other EDs. THE CONCLUSION: BP2 acts as ERalpha and ERbeta
      agonist mimicking effects of E2, while the effects of BPA and DBP are not pure
      estrogenic.

PMID- 15458796
TI  - Endocrine activity and developmental toxicity of cosmetic UV filters--an update.
AB  - UV filters represent a new class of endocrine active chemicals. In vitro, 8/9
      chemicals showed estrogenic (MCF-7 cells), and 2/9 antiandrogenic activity (MDA
      kb2 cells). Six/nine filters (benzophenone (Bp)-1, Bp-2, Bp-3, 3-benzylidene
      camphor (3-BC), 4-methylbenzylidene camphor (4-MBC), octyl-methoxycinnamate
      (OMC)) increased uterine weight in immature rats. 3-Benzylidene camphor and 4-MBC
      displaced 16alpha125I-estradiol from human estrogen receptor (ER)beta, not
      ERalpha. Developmental toxicity of 4-MBC (0.7-47 mg/kg body weight/day) and 3-BC
      (0.24-7 mg/kg), administered in chow was investigated in Long Evans (LE) rats.
      Weight gain of pregnant rats was reduced only by 3-BC, early postnatal survival
      rate and thymus weight by both compounds at higher doses. 4-Methylbenzylidene
      camphor and 3-BC delayed male puberty, and dose-dependently affected reproductive
      organ weights of adult male and female F1 offspring, with partly different effect
      patterns. Thyroid weight was increased by higher 4-MBC doses. Tissue-specific
      changes in mRNA levels of estrogen-regulated genes in prostate, uterus and brain
      regions, determined by real-time PCR, and in their response to acute estradiol
      challenge in adult gonadectomized offspring were observed. Lowest effective doses
      were 0.24 mg/kg/day for 3-BC and 7 mg/kg/day for 4-MBC. Fat tissue levels at 7
      mg/kg 4-MBC (GC-MS) approached the range of UV filters in fish (Nagtegaal et al.,
      1997; Balmer et al., 2004).

PMID- 15458797
TI  - Effects of estradiol, benzophenone-2 and benzophenone-3 on the expression pattern
      of the estrogen receptors (ER) alpha and beta, the estrogen receptor-related
      receptor 1 (ERR1) and the aryl hydrocarbon receptor (AhR) in adult ovariectomized
      rats.
AB  - The estrogen receptors (ERs) are members of a super family of ligand-activated
      transcription factors mediating estrogenic responses. A close functional kinship
      was found for the structurally related estrogen receptor-related receptor1
      (ERR1), a constitutively active transcription factor. The aryl hydrocarbon
      receptor (AhR) mediates the toxic and estrogenic effects of a wide variety of
      environmental contaminants and industrial pollutants. Both the ERR1 and the AhR
      are known to modulate the ER's signalling pathways in multiple ways. Organic
      chemicals with a certain structural relationship to steroid hormones often induce
      a tissue- or cell-specific variety of responses distinct from estrogenic
      responses and this may involve ERR1 and AhR. The UV-screens benzophenone-2 and
      benzophenone-3 (BP2, BP3), structurally related to known steroid receptor
      ligands, are used in cosmetics and plastics to improve product stability and
      durability. Both BP2 and BP3 were shown to exert uterotrophic effects and BP2 was
      shown to bind to the estrogen receptors. Whether such effects are also exerted in
      other organs is unknown. Therefore, an approach to a multi-organic risk
      assessment for these substances was made by measuring the gene-expression of the
      four mentioned receptors in the pituitary, the uterus and the thyroid after a
      five-day treatment in comparison to estradiol. Though BP2 seems to exert an
      estrogen-like effect while BP3 does not, there are regulatory effects on receptor
      expression for both substances that indicate a kind of endocrine disruption that
      is not assessed by "classical" estrogenic markers.

PMID- 15458798
TI  - Effect of oral intake of dibutyl phthalate on reproductive parameters of Long
      Evans rats and pre-pubertal development of their offspring.
AB  - To investigate the influence of dibutyl phtalate (DBP) given in a soy-free rat
      chow on pre-pubertal development, 46 Long Evans female rats 2-month-old were
      divided into three experimental groups and fed three different chows: (1)
      control; (2) DP 0.61 g/kg chow (12 mg/kgrat/day); (3) DP 2.5 g/kg chow (50 mg/kg
      rat/day) for 2 months. While under this treatment, they were mated and their
      offspring studied. Litter size and female:male ratio were recorded. At 14 days of
      age 6, male pups of each group were sacrificed and testis and thymus were excised
      and weighed. Pups were weaned at 22 days of age and continued into three
      experimental groups according to diet. From day 22 onwards, vaginal opening,
      occurrence of first estrous, and pre-putial separation were recorded. RESULTS:
      The percent of pregnancies showed a marked decrease in group 3, while no
      difference was observed between groups 1 and 2. Sex prevalence and litter size
      were not affected by the different diets. Pup survival showed a decrease when
      mothers were fed diet 2, but it was similar in diets 1 and 3. Pup weights on day
      2 showed an evident (P < 0.05) reduction in groups 2 and 3, the decrease being
      more marked (P < 0.001) in group 3. On day 6, pups of group 2 showed lower
      weights (P < 0.01) as compared with the other groups. Weight gain was
      significantly higher in pups of group 3. Eye opening was not affected by the
      different diets. Fourteen-day-old male pups' relative weight of thymus and testis
      showed a decrease in animals whose mothers had been fed diets 2 and 3. Vaginal
      opening and occurrence of first estrous showed an evident delay (P < 0.05; P <
      0.01) in females fed diets 2 and 3. Significant differences (P < 0.001) in pre
      putial separation were observed between treated and untreated groups. CONCLUSION:
      Offspring pre-pubertal development seems to be affected by oral intake of DBP by
      their mothers during pregnancy, the effects being more evident in the
      reproductive development of male pups.

PMID- 15458799
TI  - Short-term appetite and energy intake following imposed exercise in 9- to 10-year
      old girls.
AB  - Short-term effects of different intensities of exercise-induced energy
      expenditure on energy intake and hunger were compared in 19 girls (10.0 +/- 0.6
      years) in three conditions: sedentary, low-intensity exercise and high-intensity
      exercise. The exercise conditions involved cycling at 50 and 75% of peak oxygen
      uptake, respectively, but were designed to evoke approximately 1.50 MJ of total
      expenditure, as estimated from continuously monitored heart rate. A maintenance
      breakfast of controlled energy intake was provided and ad libitum energy intake
      was measured at lunch and dinner. Differences in energy intake relative to
      expenditure, between 09:30 and 17:00, were calculated by subtracting energy
      expenditure from energy intake (energy difference). Hunger, fullness and
      prospective consumption were rated before and after meals and exercise sessions.
      Lunch energy intake was significantly less after low-intensity exercise than
      after high-intensity exercise. Energy expenditure was greater in the exercise
      conditions than when sedentary and the energy difference was more positive in the
      sedentary condition than in each of the exercise conditions. At mid-afternoon,
      rated prospective consumption was less after the high-intensity exercise. The
      imposition of energy expenditure through exercise of either low or high intensity
      resulted in no detectable increase in energy intake in the short term.

PMID- 15458800
TI  - Choosing organics: a path analysis of factors underlying the selection of organic
      food among Australian consumers.
AB  - Path analysis of attitudinal, motivational, demographic and behavioural factors
      influencing food choice among Australian consumers who had consumed at least some
      organic food in the preceding 12 months showed that concern with the naturalness
      of food and the sensory and emotional experience of eating were the major
      determinants of increasing levels of organic consumption. Increasing consumption
      was also related to other 'green consumption' behaviours such as recycling and to
      lower levels of concern with convenience in the purchase and preparation of food.
      Most of these factors were, in turn, strongly affected by gender and the level of
      responsibility taken by respondents for food provisioning within their
      households, a responsibility dominated by women. Education had a slightly
      negative effect on the levels of concern for sensory and emotional appeal due to
      lower levels of education among women. Income, age, political and ecological
      values and willingness to pay a premium for safe and environmentally friendly
      foods all had extremely minor effects.

PMID- 15458801
TI  - Preference for natural: instrumental and ideational/moral motivations, and the
      contrast between foods and medicines.
AB  - Preference for natural refers to the fact that in a number of domains, especially
      food, people prefer natural entities to those which have been produced with human
      intervention. Two studies with undergraduate students and representative American
      adults indicate that the preference for natural is substantial, and stronger for
      foods than for medicines. Although healthfulness is often given as a reason for
      preferring natural foods, even when healthfulness or effectiveness (for
      medicines) of the natural and artificial exemplars is specified as equivalent,
      the great majority of people who demonstrate a preference for natural continue to
      prefer natural. In addition, when the natural and artificial exemplars are
      specified to be chemically identical, a majority of people who prefer natural
      continue to prefer it. This suggests that a substantial part of the motivation
      for preferring natural is ideational (moral or aesthetic), as opposed to
      instrumental (healthiness/effectiveness or superior sensory properties).

PMID- 15458802
TI  - Feared food in dieting and non-dieting young women: a preliminary validation of
      the Food Phobia Survey.
AB  - The Food Phobia Survey (FPS) is a recently developed clinical instrument designed
      to identify foods that are avoided out of fear or guilt by eating disordered
      individuals. The measure has potential utility in clinical settings for several
      purposes: the assessment of current food selection and food-related concerns; the
      construction of individual hierarchies for graded exposure; and the evaluation of
      treatment outcomes with reference to fear and avoidance of food items. It is
      comprised of 180 commonly eaten foods rated on three dimensions: fear/guilt,
      appeal in the absence of weight concern, and frequency of consumption. Dieting
      and non-dieting college women were compared to provide preliminary data on the
      FPS from a non-clinical population. The FPS yielded findings convergent with
      other data on forbidden foods and discriminated between dieters and non-dieters.
      For both groups, the perception that foods were fattening was correlated with
      increased fear/guilt, with dieters showing significantly greater increases in
      ratings of fear/guilt and number of feared foods with increments in the perceived
      'fatteningness' of food items.

PMID- 15458803
TI  - Non food-related environmental stimuli induce increased meal intake in healthy
      women: comparison of television viewing versus listening to a recorded story in
      laboratory settings.
AB  - The objective of the present study, performed under laboratory conditions, was to
      assess the impact of two non food-related environmental stimuli (television and
      auditory stimulus) on meal intake. Normal weight women (N = 48) ate lunch in the
      laboratory once a week for four weeks. All lunches were identical and included
      popular traditional foods, of which participants could eat ad libitum. The first
      and last lunches were eaten in the absence of the environmental stimuli (control
      conditions); in the other two tests, presented in random order, subjects ate
      while either watching television or listening to a recorded story. Energy intakes
      were determined for each meal, as were ratings of hunger, satiety and meal
      palatability. Subjects filled out the Three Factor Eating Questionnaire at the
      end of the meal series. Meal size was significantly larger in the presence of
      both environmental stimuli than in both control conditions (+11.6%, 280 kJ, p <
      0.01). Television viewing induced a significant stimulation of intake, equal to,
      but not greater than the effect of the auditory stimulus. Ratings of hunger,
      satiety, and palatability were not significantly different between conditions,
      despite the differences in intake. These results suggest that environmental, non
      food-related stimuli could stimulate intake regardless of hunger-satiety or
      palatability conditions. Environmental stimulation of eating should be tested in
      other populations, eg subjects with weight control problems, and other
      conditions, e.g. free-living.

PMID- 15458804
TI  - Energy intake associated with television viewing in adolescents, a cross
      sectional study.
AB  - The present study examines the energy intake resulting from eating snacks and
      drinking energy containing drinks while watching television. 2546 first and
      fourth year students in a random sample of 15 secondary schools in Flanders,
      Belgium received quantifiable, closed survey questions about average weekly TV
      viewing volume and about eating five types of snacks and drinking two types of
      soft drinks. On an average, the respondents watched 22:27 h of television per
      week (SD = 11:53). Only 3.5% of the adolescents never eat snacks or drink soft
      drinks while they watch TV. Estimated daily energy intake accompanying TV viewing
      amounts to 19% of the Belgian average energy allowance (AEA) in boys and between
      12 and 14% of AEA in girls. On an average 1 h of watching television equals the
      consumption of 653 kJ.

PMID- 15458805
TI  - Repetitive exposures to a surrogate nipple providing nutritive and non-nutritive
      fluids: effects on suckling behavior of the newborn rat.
AB  - Responsiveness to a surrogate nipple providing water, 0.1% saccharin, 10%
      sucrose, pedialyte, or milk was tested in naive-to-suckling newborn rats during
      six 10-min exposures, one every 1.5 h over a 7.5 h period. Across a succession of
      exposures, newborn rats repeatedly attached to and ingested milk from a surrogate
      nipple, yielding significant body weight gain and increased concentration of
      blood plasma glucose. Initially, pups ingested considerable amounts of saccharin
      and sucrose, but then dramatically decreased their consumption of these fluids
      across the experimental sessions. Intake of milk was significantly higher than
      that of all other substances. Blood glucose concentration in pups treated with
      water, saccharin, sucrose, and pedialyte did not differ significantly from that
      of non-treated pups. The present data suggest a potential contribution of a
      fluid's palatability and nutritive value in the persistence and efficacy of diet
      intake for neonatal rats in the context of suckling behavior.

PMID- 15458806
TI  - Testing relationships between values and food-related lifestyle: results from two
      European countries.
AB  - The value survey developed by Shalom Schwartz (1992) has been applied in many
      countries with different purposes. In this study we present a new way of
      analysing the theoretically assumed circumplex structure of Schwartz value survey
      and its relationships to other constructs, here the instrument food-related
      lifestyle. In two countries; Germany and Spain, data were collected. In each
      country 1000 interviews were carried out where consumers were asked about their
      value priorities and about their food-related lifestyle. The study provides new
      insights into the way values influence peoples' food-related lifestyle in Germany
      and Spain, and the results validate both the Schwartz value survey and the food
      related lifestyle instrument in a nomological sense, since significant and
      meaningful relationships were found between the two constructs.

PMID- 15458807
TI  - Chewing gum can produce context-dependent effects upon memory.
AB  - Two experiments examined whether chewing spearmint gum can affect the initial
      learning or subsequent recall of a word list. Comparing those participants in
      Experiment 1 who chewed gum at the learning or the recall phases showed that
      chewing gum at initial learning was associated with superior recall. In addition,
      chewing gum led to context-dependent effects as a switch between gum and no gum
      (or no gum and gum) between learning and recall led to poorer performance.
      Experiment 2 provided evidence that sucking gum was sufficient to induce some of
      the same effects as chewing.

PMID- 15458808
TI  - Role of glucose in chewing gum-related facilitation of cognitive function.
AB  - This study tests the hypothesis that chewing gum leads to cognitive benefits
      through improved delivery of glucose to the brain, by comparing the cognitive
      performance effects of gum and glucose administered separately and together.
      Participants completed a battery of cognitive tests in a fully related 2 x 2
      design, where one factor was Chewing Gum (gum vs. mint sweet) and the other
      factor was Glucose Co-administration (consuming a 25 g glucose drink vs.
      consuming water). For four tests (AVLT Immediate Recall, Digit Span, Spatial Span
      and Grammatical Transformation), beneficial effects of chewing and glucose were
      found, supporting the study hypothesis. However, on AVLT Delayed Recall,
      enhancement due to chewing gum was not paralleled by glucose enhancement,
      suggesting an alternative mechanism. The glucose delivery model is supported with
      respect to the cognitive domains: working memory, immediate episodic long-term
      memory and language-based attention and processing speed. However, some other
      mechanism is more likely to underlie the facilitatory effect of chewing gum on
      delayed episodic long-term memory.

PMID- 15458809
TI  - Chewing gum and cognitive performance: a case of a functional food with function
      but no food?
AB  - Recent reports suggest that enhancement of memory performance while chewing gum
      is a fairly robust phenomenon. The processes underlying the effect are not known,
      but may involve glucose delivery, context-dependent effects and arousal
      mechanisms amongst others. This brief commentary outlines the main findings from
      these studies and raises some issues regarding interpretation, methodology and
      future research directions.

PMID- 15458810
TI  - How does chewing gum affect cognitive function? Reply to Scholey (2004).
AB  - Cognitive effects of glucose from chewing gum and other mechanisms can be
      investigated further when factors like the flavouring of the gum and the
      participants' familiarity with gum chewing are assessed.

PMID- 15458811
TI  - Effects of gum chewing on memory and attention: reply to Scholey (2004).
AB  - Recent studies have reported varying results regarding cognitive performance
      while chewing gum. The differences between the results of these studies may be
      explained by methodological and statistical factors. Future studies are needed to
      assess various aspects of cognitive functioning using extensive standardised
      neuropsychological test batteries, adequate experimental designs and appropriate
      statistical methods.

PMID- 15458813
TI  - Omega-3 fatty acids in cellular membranes: a unified concept.
AB  - The Omega-3 fatty acid DHA (docosahexaenoic acid, 22:6) and its sister molecule
      EPA (eicosapentaenoic acid, 20:5) are highlighted here. These highly unsaturated
      fatty acids are widespread in nature, especially in the marine environment, and
      are essential in membranes ranging from deep sea bacteria to human neurons.
      Studies of DHA/EPA in bacteria have led to a working model on the structural
      roles of these molecules and are described in this review. The main points are:
      (a) genomic analysis shows that genes encoding the DHA/EPA pathways are similar,
      supporting the idea that structural roles in bacteria might be similar, (b)
      biochemical analysis shows that DHA and EPA are produced in bacteria by a
      polyketide process distinct from the pathway of plants and animals; this allows
      DHA and EPA to be produced in anaerobic or oxygen-limited environments, (c)
      regulatory systems triggered by temperature and pressure have been identified and
      studied, and add to the understanding of the roles of these molecules, (d)
      DHA/EPA bacteria are located almost exclusively in the marine environment,
      raising the prospect of an important linkage between membrane processes and
      marine conditions, (e) physiological studies of an EPA recombinant of E. coli
      show that EPA phospholipids contribute essential fluidity to the bilayer and that
      an EPA-enriched membrane supports a respiratory lifestyle dependent on proton
      bioenergetics; the EPA recombinant displays other physiological properties likely
      attributed to high levels of EPA in the bilayer, and (f) chemical studies such as
      chemical dynamic modeling support the idea that DHA and presumably EPA contribute
      hyperfluidizing properties to the membrane. We hypothesize that DHA/EPA
      phospholipids contribute fluidity and other properties to the bilayer which
      distinguish these highly unsaturated chains from monounsaturates and
      polyunsaturates such as 18:2 and 18:3. We further hypothesize that the structural
      properties of DHA/EPA functioning in bacteria are also harnessed by higher
      organisms for enhancing crucial membrane processes including photosynthesis and
      energy transduction.

PMID- 15458814
TI  - Arsenolipids.
AB  - Natural arsenolipids are analogues of neutral lipids, like monoglycerides,
      glycolipids, phospho- and also phosphonolipids. They have been found in
      microorganisms, fungi, plants, lichens, in marine mollusks, sponges, other
      invertebrates, and in fish tissues. This review presented structures of natural
      arsenolipids (and derivatives), their distribution, biogenesis in algae and
      invertebrates, synthesis, and also biological activity. Arsenolipids are thought
      to be end products of arsenate detoxification processes, involving reduction and
      oxidative methylation and adenosylation. The proposed biogenesis of arsenolipids
      is based on the natural occurrence of arsenic metabolites, and all the
      intermediates in the proposed pathway have been identified as natural products of
      algal origin. Different arseno species are shown to be inhibitors of glycerol
      kinase, bovine carbonic anhydrase, and also is an effective therapy for acute
      promyelocytic leukemia, and there has been promising activity noted in other
      hematologic and solid tumors. Arsonoliposomes demonstrated high anti-trypanosomal
      activity against Trypanosoma brucei and inhibit growth of some types of cancer
      cells (HL-60,C6 and GH3).

PMID- 15458815
TI  - Matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) mass
      spectrometry in lipid and phospholipid research.
AB  - The interest in the analysis of lipids and phospholipids is continuously
      increasing due to the importance of these molecules in biochemistry (e.g. in the
      context of biomembranes and lipid second messengers) as well as in industry.
      Unfortunately, commonly used methods of lipid analysis are often time-consuming
      and tedious because they include previous separation and/or derivatization steps.
      With the development of "soft-ionization techniques" like electrospray ionization
      (ESI) or matrix-assisted laser desorption and ionization time-of-flight (MALDI
      TOF), mass spectrometry became also applicable to lipid analysis. The aim of this
      review is to summarize so far available experiences in MALDI-TOF mass
      spectrometric analysis of lipids. It will be shown that MALDI-TOF MS can be
      applied to all known lipid classes and the characteristics of individual lipids
      will be discussed. Additionally, some selected applications in medicine and
      biology, e.g. mixture analysis, cell and tissue analysis and the determination of
      enzyme activities will be described. Advantages and disadvantages of MALDI-TOF MS
      in comparison to other established lipid analysis methods will be also discussed.

PMID- 15458816
TI  - Protein interactions with platinum-DNA adducts: from structure to function.
AB  - Because of the efficacy of cisplatin and carboplatin in a wide variety of
      chemotherapeutic regimens, hundreds of platinum(II) and platinum(IV) complexes
      have been synthesized and evaluated as anticancer agents over the past 30 years.
      Of the many third generation platinum compounds evaluated to date, only
      oxaliplatin has been approved for clinical usage in the United States. Thus, it
      is important to understand the mechanistic basis for the differences in efficacy,
      mutagenicity and tumor range between cisplatin and oxaliplatin. Cisplatin and
      oxaliplain form the same types of adducts at the same sites on DNA. The most
      abundant adduct for both compounds is the Pt-GG intrastrand diadduct. Cisplatin
      GG adducts are preferentially recognized by mismatch repair proteins and some
      damage-recognition proteins, and this differential recognition of cisplatin- and
      oxaliplatin-GG adducts is thought to contribute to the differences in
      cytotoxicity and tumor range of cisplatin and oxaliplatin. A detailed kinetic
      analysis of the insertion and extension steps of dNTP incorporation in the
      vicinity of the adduct shows that both pol beta and pol eta catalyze translesion
      synthesis past oxaliplatin-GG adducts with greater efficiency than past cisplatin
      GG adducts. In the case of pol eta, the efficiency and fidelity of translesion
      synthesis in vitro is very similar to that previously observed with cyclobutane
      TT dimers, suggesting that pol eta is likely to be involved in error-free bypass
      of Pt adducts in vivo. This has been confirmed for cisplatin by comparing the
      cisplatin-induced mutation frequency in human fibroblast cell lines with and
      without pol eta. Thus, the greater efficiency of bypass of oxaliplatin-GG adducts
      by pol eta is likely to explain the lower mutagenicity of oxaliplatin compared to
      cisplatin. The ability of these cellular proteins to discriminate between
      cisplatin and oxaliplatin adducts suggest that there exist significant
      conformational differences between the adducts, yet the crystal structures of the
      cisplatin- and oxaliplatin-GG adducts were very similar. We have recently solved
      the solution structure of the oxaliplatin-GG adduct and have shown that it is
      significantly different from the previously published solution structures of the
      cisplatin-GG adducts. Furthermore, the observed differences in conformation
      provide a logical explanation for the differential recognition of cisplatin and
      oxaliplatin adducts by mismatch repair and damage-recognition proteins. Molecular
      modeling studies are currently underway to analyze the mechanistic basis for the
      differential bypass of cisplatin and oxaliplatin adducts by DNA polymerases.

PMID- 15458817
TI  - Effect of the geometry of the central coordination sphere in antitumor trinuclear
      platinum complexes on DNA binding.
AB  - Polynuclear platinum compounds comprise a unique class of anticancer agents with
      chemical and biological properties different from mononuclear platinum drugs. The
      lead compound of this class is bifunctional trinuclear platinum complex [[trans
      PtCl(NH(3))(2)](2)mu-trans-Pt(NH(3))(2)[H(2)N(CH(2))(6)NH(2)](2)](4+)
      (1,0,1/t,t,t, BBR 3464). Interestingly, the geometry of the coordination spheres
      in this compound affects potency. For example, the central cis unit of [[trans
      PtCl(NH(3))(2)](2)mu-cis-Pt(NH(3))(2)[H(2)N(CH(2))(6)NH(2)](2)](4+) (1,0,1/t,c,t,
      BBR 3499) results in substantially reduced cytotoxicity. It has been shown that
      the interactions of polynuclear platinum drugs with target DNA are distinct from
      the mononuclear-based cisplatin family. In the present work the DNA binding of
      1,0,1/t,c,t in cell-free media was examined by the methods of molecular
      biophysics and compared to the binding of 1,0,1/t,t,t. The binding of 1,0,1/t,c,t
      is slower and less sequence specific. 1,0,1/t,c,t also forms on DNA long-range
      delocalized intrastrand and interstrand cross-links similarly as 1,0,1/t,t,t,
      although the frequency of interstrand adducts is markedly enhanced. Importantly,
      the adducts of 1,0,1/t,c,t distort DNA conformation and are repaired by cell-free
      extracts considerably more than the adducts of 1,0,1/t,t,t. It has been suggested
      that the unique properties of long-range interstrand cross-links of bifunctional
      trinuclear platinum complexes and resulting conformational alterations in DNA
      have critical consequences for their antitumor effects.

PMID- 15458818
TI  - Triplex mediated delivery of a platinum complex to a specific DNA target site.
AB  - Tethering an ethylene diamine linker to the 5' terminus of an oligothymidine
      sequence provides a site for complexation with K(2)PtCl(4). Due to the low
      reactivity of dT toward a platinum source, we chose dT(8) and dT(15) as our
      initial synthetic targets for platination. Post-synthetic reaction of the
      platinum reagent with the diamino oligothymidine generates the diamino dichloro
      platinum-DNA conjugate that can be used for DNA duplex targeting by
      oligodeoxyncleotide-mediated triplex formation. The dT(8) sequence is not
      sufficiently long to facilitate triplex formation and Pt-cross-linking, whereas
      with a dT(15) sequence cross-linking between the third strand and the duplex
      occurs exclusively with the duplex target strand directly involved in triplex
      formation. No examples of cross-linking to the complementary target strand, or of
      cross-linking to both target strands are observed. Most efficient cross-linking
      occurs when the dinucleotide d(GpG) is present in the target strand and no cross
      linking occurs with the corresponding 7-deazaG dinucleotide target. Cross-linking
      is also observed when dC or dA residues are present in the target strand, or even
      with a single dG residue, but it is not observed in any cases to dT residues.
      Triplex formation provides the ability to target specific sequences of double
      stranded DNA and the orientational control arising from triplex formation is
      sufficient to alter the binding preferences of platinum. Conjugates of the type
      described here offer the potential of delivering a platinum complex to a specific
      DNA site.

PMID- 15458819
TI  - Potential adenine and minor groove binding platinum complexes.
AB  - This paper is a focused review of our recent efforts to produce multi-nuclear
      platinum anti-cancer complexes that preferentially target adenine residues in
      DNA. Multi-nuclear platinum complexes, like cisplatin, predominantly form
      covalent adducts with guanine bases; however, controlling the pre-covalent
      binding association of the metal complex may modify this preference. NMR
      experiments, using oligonucleotides, indicate that multi-nuclear complexes linked
      by flexible diaminoalkanes will pre-associate in the DNA minor groove at A/T rich
      regions. Despite this pre-covalent binding preference, these complexes still
      predominantly covalently bind guanine residues. However, using 4,4'
      dipyrazolylmethane (dpzm) as a linking ligand produces a dinuclear platinum
      complex, trans-[[PtCl(NH(3))(2)](2)mu-dpzm](2+), that covalently binds DNA with a
      preference for adenine bases. In vitro transcription assays also demonstrate that
      the dpzm-based complex covalently binds within an A/T rich region of the 512 base
      pair segment of DNA used for the study.

PMID- 15458820
TI  - Comparison of structural effects in 1,4 DNA-DNA interstrand cross-links formed by
      dinuclear and trinuclear platinum complexes.
AB  - The novel anticancer drug ([[trans-PtCl(NH(3))(2)](2)-mu-[trans
      Pt(NH(3))(2)(NH(2)(CH(2))(6)NH(2))(2)]](NO(3))(4)) (BBR3464, 1,0,1/t,t,t, TPC)
      forms a 1,4-interstrand cross-linked adduct with the self-complementary DNA
      octamer 5'-d(ATG*TACAT)(2)-3', with the two platinum atoms coordinated in the
      major groove at N7 positions of guanines four base pairs apart on opposite DNA
      strands [Y. Qu, N.J. Scarsdale, M.-C. Tran, N. Farrell, J. Biol. Inorg. Chem. 8
      (2003) 19-28]. The structure of the identical cross-link formed by the dinuclear
      [[trans-PtCl(NH(3))(2)](2)-mu-NH(2)(CH(2))(6)NH(2)]](NO(3))(2) (BBR3005, 1,1/t,t,
      DPC) was examined for comparison. The adduct was characterized and analyzed by
      MS, UV and NMR spectroscopy. NMR analysis of the adduct shows platination of the
      unique guanine residues. The strong H8/H1' intraresidue cross-peaks observed for
      all purine residues (A1, G3, A5 and A7) are consistent with a syn-conformation of
      the nucleoside unit in all cases. Thus, the structure resembles closely that
      formed by the trinuclear compound. Further confirmation of this similarity comes
      from the increase in melting temperature (66 degrees for DPC, 60 degrees for TPC,
      22 degrees for free oligonucleotide). Since DNA is the principal target in vivo
      for these Pt cross-linking agents, the unique structural perturbations induced by
      these cross-links may be related to the increased cytotoxicity and antitumor
      activity of polynuclear platinum compounds as compared to cisplatin (cis-DDP).
      The similarity in the structures suggests opportunities to "deliver" the cross
      link in a more efficient manner than the current clinically tested drug.

PMID- 15458821
TI  - Synthesis and DNA conformational changes of non-covalent polynuclear platinum
      complexes.
AB  - Polynuclear platinum compounds demonstrate many novel phenomena in their
      interactions with DNA and proteins as well as novel anti-cancer activities.
      Previous studies indicated that the high positive charge and the non-coordinated
      "central linker" of the polynuclear compounds could have major contributions to
      these features. Therefore, a series of non-covalent polynuclear platinum
      complexes, [[Pt(NH(3))(3)](2)-mu-Y](n+) (Y=polyamine linker or [trans
      Pt(NH(3))(2)(H(2)N(CH(2))(6)NH(2))(2)]) was synthesized and the DNA interactions
      of these platinum complexes were investigated. The conformational changes induced
      by these compounds in polymer DNA were studied by circular dichroism and the
      reversibility of the transition was tested by subsequent titration with the DNA
      intercalating agent ethidium bromide (EtBr). Fluorescent quenching was also used
      to assess the ability of EtBr to intercalate into A and Z-DNA induced by the
      compounds. The non-covalent polynuclear platinum complexes induced both B-->A and
      B-->Z conformational changes in polymer DNA. These conformational changes were
      partially irreversible. The platinum compound with the spermidine linker,
      [[Pt(NH(3))(3)](2)-mu-spermidine-N(1),N(8)]Cl(5).2H(2)O, is more efficient in
      inducing the conformational changes of DNA and it is less reversible than
      complexes with other linkers. The melting point study showed that the non
      covalent polynuclear platinum complexes stabilized the duplex DNA and the higher
      the electrical charge of the complexes the greater the stabilization observed.

PMID- 15458822
TI  - A pleiotropic defect reducing drug accumulation in cisplatin-resistant cells.
AB  - The resistance of tumors to cisplatin remains a major cause of treatment failure
      in cancer patients. Multiple, simultaneous alterations are frequently encountered
      in cancer cells selected for cisplatin resistance. To determine whether the
      complex phenotype results from many different cellular alterations, single-step
      variants were isolated based on one-step selection in cisplatin. Reduced drug
      accumulation is a common feature of cisplatin-resistant (CP-r) cancer cells,
      which is probably caused by one or more dominant genes. Pulse-chase labeling and
      pulse-chase biotinylation of cell surface proteins suggest that membrane protein
      mislocalization occurs in CP-r cells, caused mainly by a defect in plasma
      membrane protein recycling, manifested also as a defect in acidification of
      lysosomes. This membrane protein mislocalization is presumed to reduce cell
      surface expression of a putative cisplatin carrier or carriers. In cells selected
      in several steps, decreased expression of folate-binding protein and arsenic
      binding proteins, and reduced endocytosis were detected in CP-r cells,
      contributing to the reduced uptake of cisplatin, methotrexate and other related
      compounds. Multiple mechanisms in CP-r cells keep cytotoxic platinum compounds
      out of cells through defective expression of cell surface proteins such as
      transporters and carriers, and decreased expression of proteins involved in
      endocytosis.

PMID- 15458823
TI  - The role of copper transporters in the development of resistance to Pt drugs.
AB  - Recent studies in yeast, mouse and human cells suggest that the conserved metal
      binding transporters of the Cu homeostasis pathway can mediate resistance to Pt
      drugs in cancer cells. This review summarizes the data available from these
      studies. The observation that cells selected for resistance to Cu or the Pt drugs
      display bidirectional cross-resistance, parallel defects in the transport of Cu
      and the Pt drugs and altered expression of Cu transporters is consistent with the
      concept that the Cu homeostasis proteins regulate sensitivity to the Pt drugs by
      influencing their uptake, efflux and intracellular distribution. This model is
      supported by the finding that when mammalian and yeast cells are genetically
      engineered to express altered levels of the Cu transporters they exhibit altered
      sensitivity to Pt drugs and are defective in intracellular Pt accumulation due to
      altered uptake and/or efflux rates. Negative associations between the expression
      of ATP7A and ATP7B and the outcome of Pt therapy further support the significance
      of the Cu homeostasis proteins as both markers of and contributors to Pt
      resistance.

PMID- 15458824
TI  - The mechanism of action of platinum(IV) complexes in ovarian cancer cell lines.
AB  - The reduction potentials, lipophilicities, cellular uptake and cytotoxicity have
      been examined for two series of platinum(IV) complexes that yield common
      platinum(II) complexes on reduction: cis-[PtCl(4)(NH(3))(2)], cis,trans,cis
      [PtCl(2)(OAc)(2)(NH(3))(2)], cis,trans,cis-[PtCl(2)(OH)(2)(NH(3))(2)],
      [PtCl(4)(en)], cis,trans-[PtCl(2)(OAc)(2)(en)] and cis,trans-[PtCl(2)(OH)(2)(en)]
      (en=ethane-1,2-diamine, OAc=acetate). As previously reported, the reduction
      occurs most readily when the axial ligand is chloride and least readily when it
      is hydroxide. The en series of complexes are marginally more lipophilic than
      their ammine analogues. The presence of axial chloride or acetate ligands results
      in a slighter higher lipophilicity compared with the platinum(II) analogue
      whereas hydroxide ligands lead to a substantially lower lipophilicity. The
      cellular uptake is similar for the platinum(II) species and their analogous
      tetrachloro complexes, but is substantially lower for the acetato and hydroxo
      complexes, resulting in a correlation with the reduction potential. The
      activities are also correlated with the reduction potentials with the tetrachloro
      complexes being the most active of the platinum(IV) series and the hydroxo being
      the least active. These results are interpreted in terms of reduction, followed
      by aquation reducing the amount of efflux from the cells resulting in an increase
      in net uptake.

PMID- 15458825
TI  - Vitamin-mediated targeting as a potential mechanism to increase drug uptake by
      tumours.
AB  - Targeted chemotherapy for cancer treatment offers a great potential advantage in
      tumour treatment due to greater specificity of delivery which leads to increased
      dose of the cytotoxin delivered to the tumour relative to the rest of the body.
      In order to achieve such selective targeted delivery one needs to identify
      generic markers that are over-expressed on the surface of tumour cells but are
      not over-expressed on normal tissue. Work of several authors has shown that some
      cells, such as those of rapidly dividing, aggressive tumours, over-express
      surface receptors involved in the uptake of vitamin B(12) [B. Rachmilewitz, M.
      Rachmilewitz, B. Moshkowitz, J. Gross, J. Lab. Clin. Med. 78 (1971) 275-279; B.
      Rachmilewitz, A. Sulkes, M. Rachmilewitz, A. Fuks, Israel J. Med. Sci. 17 (1981)
      874-879] or folate [P. Garin-Chesa, I. Campbell, P.E. Saigo, J.L. Lewis Jr., L.J.
      Old, W.J. Rettig, Am. J. Pathol. 142 (1993) 557-567; O.C. Boerman, C.C. van
      Niekerk, K. Makkink, T.G.J.M. Hanselaar, P. Kenemans, L.G. Poels, Int. J.
      Gynecol. Pathol. 10 (1991) 15-25; G. Toffoli, C. Cernigoi, A. Russo, A. Gallo, M.
      Bagnoli, M. Boiocchi, Int. J. Cancer 74 (1997) 193-194; J.A. Reddy, D. Dean, M.D.
      Kennedy, P.S. Low, J. Pharm. Sci. 88 (1999) 1112-1118; J.A. Reddy, P.S. Low,
      Crit. Rev. Ther. Drug Carrier Syst. 15 (1998) 587-627; G.J. Russell-Jones, K.
      McTavish, J.F. McEwan, in: Proceedings of the 2nd International Symposium on
      Tumor Targeted Delivery Systems, 2002]. Furthermore the degree of over-expression
      has been found to correlate with the stage of tumour growth, with the highest
      levels found on stage IV carcinomas. Using fluorescently-labelled polymers to
      which are linked the targeting agents, vitamin B(12), folate or biotin, the
      relative uptake of these polymers into various types of tumour cell lines grown
      both in vitro and in vivo has been examined. These studies have shown that while
      some tumour types do NOT over-express receptors involved in vitamin uptake, most
      tumour types over-express receptors for folate, or vitamin B(12). In either case
      there is also a greatly increased expression of a yet to be identified biotin
      receptor. In cases of receptor over-expression, binding of the targeted
      fluorochrome leads to rapid internalization of these molecules within the cells
      to levels that are two to thirty times higher than with non-targeted polymers.
      Using a number of cancer models, these studies were extended further and it was
      found that the increased expression of receptors also leads to increased levels
      of killing with targeted cytotoxins. Thus the preliminary data described suggests
      that the use of vitamins as targeting agents has enormous potential for use in
      cancer diagnosis and chemotherapy.

PMID- 15458826
TI  - Gold complexes inhibit mitochondrial thioredoxin reductase: consequences on
      mitochondrial functions.
AB  - The effects of gold(I) complexes (auranofin, triethylphosphine gold and
      aurothiomalate), gold(III) complexes ([Au(2,2'-diethylendiamine)Cl]Cl(2), [(Au(2
      (1,1-dimethylbenzyl)-pyridine) (CH(3)COO)(2)], [Au(6-(1,1-dimethylbenzyl)-2,2'
      bipyridine)(OH)](PF(6)), [Au(bipy(dmb)-H)(2,6-xylidine)](PF(6))), metal ions
      (zinc and cadmium acetate) and metal complexes (cisplatin, zinc pyrithione and
      tributyltin) on mitochondrial thioredoxin reductase and mitochondrial functions
      have been examined. Both gold(I) and gold(III) complexes are extremely efficient
      inhibitors of thioredoxin reductase showing IC(50) ranging from 0.020 to 1.42
      microM while metal ions and complexes not containing gold are less effective,
      exhibiting IC(50) going from 11.8 to 76.0 microM. At variance with thioredoxin
      reductase, auranofin is completely ineffective in inhibiting glutathione
      peroxidase and glutathione reductase, while gold(III) compounds show some effect
      on glutathione peroxidase. The mitochondrial respiratory chain is scarcely
      affected by gold compounds while the other metal complexes and metal ions, in
      particular zinc ion and zinc pyrithione, show a more marked inhibitory effect
      that is reflected on a rapid induction of membrane potential decrease that
      precedes swelling. Therefore, differently from gold compounds, the various metal
      ions and metal complexes exert their effect on different targets indicating a
      lower specificity. It is concluded that gold compounds are highly specific
      inhibitors of mitochondrial thioredoxin reductase and this action influences
      other functions such as membrane permeability properties. Metal ions and metal
      complexes markedly inhibit the activity of thioredoxin reductase although to an
      extent lower than that of gold compounds. They also inhibit mitochondrial
      respiration, decrease membrane potential and, finally, induce swelling.

PMID- 15458827
TI  - Mitochondrial permeability transition induced by dinuclear gold(I)-carbene
      complexes: potential new antimitochondrial antitumour agents.
AB  - Seven dinuclear gold(I) complexes of bidentate N-heterocyclic carbene ligands
      have been evaluated for their ability to induce mitochondrial membrane
      permeabilisation (MMP) in isolated rat liver mitochondria. Six of the compounds,
      at concentrations of 10 microM, induced Ca(2+)-sensitive MMP as evidenced by
      mitochondrial swelling. In the absence of low concentrations of exogenous Ca(2+),
      the compounds were either inactive or their activity was significantly decreased.
      The mitochondrial swelling was completely blocked by the addition of cyclosporin
      A, a well established inhibitor of the mitochondrial permeability transition pore
      (MPT) that is believed to be responsible for MMP. The rates and levels of uptake
      of these compounds into mitochondria were estimated by measuring mitochondrial Au
      levels using inductively coupled plasma optical emission spectroscopy.
      Significant differences were found in the levels at which the different compounds
      accumulated in the mitochondria, but these differences did not correlate with the
      rate at which they induced mitochondrial swelling. These results suggest that the
      mechanism by which MMP is induced by these lipophilic cationic Au(I)-carbene
      complexes is not purely a function of the level of compound accumulation.
      Instead, a more specific mechanism, possibly involving disruption of the function
      of a particular enzyme, or interaction with a MPT component, appears to be more
      likely.

PMID- 15458828
TI  - TGFbeta1 regulation and collagen-release-independent connective tissue re
      modelling by the ruthenium complex NAMI-A in solid tumours.
AB  - PURPOSE: The objective of this study is to evaluate the fibrotic process induced
      in vivo by NAMI-A in mice with solid tumours. In addition, the in vitro effects
      of NAMI-A on collagen fibres and the expression of TGFbeta1 in TS/A
      adenocarcinoma cells, NIH/3T3 fibroblasts and co-culture of fibroblasts and
      tumour cells have also been studied. METHODS: Collagen fibres release was assayed
      in supernatant of culture cells treated with 0.1 and 0.01 mM NAMI-A. TGFbeta1 was
      detected by RT-PCR and immunoblot on cellular lysates. RESULTS: NAMI-A, given to
      mice bearing MCa mammary carcinoma at advanced stages of growth, increased the
      thickness of connective tissue and induced recruitment of leukocytes,
      particularly in the peritumour capsule. In vitro NAMI-A stimulated collagen
      production by NIH/3T3 fibroblasts and decreased collagen release by TS/A tumour
      cells after prolonged exposure, either after single cell treatment or in co
      cultures. In co-cultures, NAMI-A, in a dose-dependent manner, down-regulated the
      expression of TGFbeta1 mRNA and protein in tumour cells and up-regulated it in
      fibroblasts. The isoform of this cytokine is involved in fibrosis, invasion and
      metastatic processes. CONCLUSIONS: These data emphasize the ability of NAMI-A to
      evoke beneficial effects from healthy cells against tumour growth and metastases.
      The contribution of fibroblasts to the fibrosis arising in tumour masses is due
      to TGFbeta1, and its down-regulation in tumour cells might explain the documented
      reduction of gelatinase release.

PMID- 15458829
TI  - Contributions from the Ninth International Symposium on Platinum Compounds in
      Cancer Chemotherapy. October 8-11, 2003. New York, New York, USA.

PMID- 15458830
TI  - Nonword repetition abilities of children who stutter: an exploratory study.
AB  - Past research has suggested that children who stutter (CWS) may have less well
      developed language skills than fluent children, and that such relative linguistic
      deficiencies may play a role in precipitating their disfluencies. However, data
      to support this position are primarily derived from results of standardized
      diagnostic inventories, which are originally designed to identify frank language
      impairment. Nonword repetition has emerged as a more sensitive measure of
      children's linguistic abilities. In this exploratory study, eight CWS (mean age
      5:10, range 4:3-8:4) were compared to eight normally developing children (ND)
      (mean age 5:9, range 4:1-8:4) in their ability to repeat the nonwords of the
      Children's Test of Nonword Repetition. CWS performed more poorly than NS on
      measures of Number of Words Correct and Number of Phoneme Errors at all nonword
      lengths, although statistical differences were observed only for 3-syllable
      nonwords. When lexical stress of the nonwords was varied to a non-English stress
      pattern, all participants repeated the stimuli with less accuracy, and the CWS
      again exhibited more errors than NS. Fluency for the CWS group did not change
      systematically with increasing nonword length. These preliminary findings are
      interpreted in light of a number of extant theories of the underlying deficit in
      childhood stuttering. We conclude that children who stutter may have diminished
      ability to remember and/or reproduce novel phonological sequences, and that
      further investigation into this possibility may shed light on the emergence and
      characteristics of childhood stuttering. EDUCATIONAL OBJECTIVES: After completing
      this activity, the learner will: (1) be able to evaluate the research support for
      a linguistic component to stuttering; (2) describe the use of nonword repetition
      as an experimental and assessment device with children with SLI and children who
      stutter; (3) suggest future directions for research to further refine the
      potential role that linguistic encoding plays in the etiology and persistence of
      stuttering.

PMID- 15458831
TI  - Social anxiety in stuttering: measuring negative social expectancies.
AB  - Much research has suggested that those who stutter are likely to be anxious.
      However, to date, little research on this topic has addressed the role of
      expectancies of harm in anxiety, which is a central construct of anxiety in
      modern clinical psychology. There are good reasons to believe that the anxiety of
      those who stutter is related to expectancies of social harm. Therefore, in the
      present study, 34 stuttering and 34 control participants completed the Fear of
      Negative Evaluation (FNE) Scale and the Endler Multidimensional Anxiety Scales
      Trait (EMAS-T). The FNE data showed a significant difference between the
      stuttering and control participants, with a large effect size. Results suggested
      that, as a group, a clinical population of people who stutter has anxiety that is
      restricted to the social domain. For the EMAS-T, significant differences between
      groups were obtained for the two subtests that refer specifically to people and
      social interactions in which social evaluation might occur (Social Evaluation and
      New/Strange Situations) but not for the subtests that contained no specific
      reference to people and social interactions (Physical Danger and Daily Routines).
      These results were taken to suggest that those who stutter differ from control
      subjects in their expectation of negative social evaluation, and that the effect
      sizes are clinically significant. The findings also suggest that the FNE and the
      EMAS-T are appropriate psychological tests of anxiety to use with stuttering
      clients in clinical settings. The clinical and research implications of these
      findings are discussed, in terms of whether social anxiety mediates stuttering or
      is a simple by-product of stuttering. Possible laboratory explorations of this
      issue are suggested, and potential Cognitive Behavior Therapy packages for
      stuttering clients who might need them are discussed. EDUCATIONAL OBJECTIVES: The
      reader will be able to: (1) explain why expectancy of social threat or harm may
      be associated with stuttering; (2) name and describe two psychological tests that
      are suitable for assessment of the social threat or harm that may be associated
      with stuttering; and (3) explain how findings for the EMAS-T test in the present
      results suggest that expectancy of social threat or harm, but not other kinds of
      negative expectancy, are associated with stuttering.

PMID- 15458832
TI  - Perceptual aspects of cluttered speech.
AB  - The purpose of this descriptive investigation was to explore perceptual judgments
      of speech naturalness, compared to judgments of articulation, language,
      disfluency, and speaking rate, in the speech of two youths who differed in
      cluttering severity. Two groups of listeners, 48 from New York and 48 from West
      Virginia, judged 93 speaking samples on 9-point scales of two cluttering speakers
      tape recorded in an earlier study [St. Louis, K. O., Myers, F. L., Cassidy, L.
      J., Michael, A. J., Penrod, S. M., Litton, B. A., et al. (1996). Efficacy of
      delayed auditory feedback for treating cluttering: Two case studies. Journal of
      Fluency Disorders, 21, 305-314]. A counterbalanced design assigned each listener
      to listen to half of the total samples and to judge naturalness and two of the
      other four attributes (i.e., articulation and language or disfluency and rate).
      Among the five attributes, rate and naturalness were perceptually least
      acceptable for both clutterers followed by articulation. Disfluency and language
      were most acceptable, although different results for the various probe tasks were
      observed for the two cluttering subjects, one severe and the other, mild
      moderate. Among other findings, the study highlights the multidimensionality of
      naturalness judgments. EDUCATIONAL OBJECTIVES: The reader will be able to: (1)
      describe differences in perceptual judgments of cluttering; (2) summarize
      features that contribute to the multidimensionality of cluttering; and (3)
      describe sources of variability in group perceptual judgments of cluttered
      speech.

PMID- 15458833
TI  - A comparative investigation of the speech-associated coping responses reported by
      adults who do and do not stutter.
AB  - The Behavior Checklist, a self-report test procedure, was administered to 42
      adults who stutter and 76 who do not in order to investigate the number,
      frequency of usage, type and nature of the responses that they reportedly employ
      to cope with the anticipation and/or presence of speech disruption. As a group,
      the participants who stutter reported a significantly greater number of speech
      associated coping responses and a greater use of them than their nonstuttering
      peers did. Moreover, factor analysis made apparent fundamental between-group
      differences in the type and nature of certain forms of the coping responses
      reported by those who stutter and those who do not. This suggests that the
      quantitative and qualitative differences in the coping responses of those who do
      and do not stutter are potentially useful with respect to differential diagnostic
      and therapeutic decision making. EDUCATIONAL OBJECTIVES: (1) The reader will be
      able to describe differences in the number, frequency and types of coping
      behaviors used by PWS and PWNS. (2) The reader will be able to list similarities
      and differences in the type and nature of coping behaviors used by PWS and PWNS.
      (3) The reader will be able to discuss the features and use of the Behavior
      Checklist, a self-report procedure for assessing the responses used by adults to
      cope with the anticipation and occurrence of speech disruption.

PMID- 15458834
TI  - Dopaminergic modulation of spontaneous inhibitory network activity in the lateral
      amygdala.
AB  - There is converging evidence that dopamine (DA) receptor activation in the
      lateral amygdala (LA) is required for the acquisition of conditioned fear.
      Powerful inhibitory circuits exist in the LA shaping the activity of excitatory
      projection neurons and controlling the induction of associative plasticity, which
      is thought to underlie fear learning. In vivo and in vitro electrophysiological
      experiments indicate that DA suppresses inhibitory transmission triggered by
      excitatory afferent input. Conversely, DA increases the excitability of
      inhibitory interneurons in the LA. However, the mechanisms by which DA modulates
      inhibitory transmission are poorly understood. Using whole-cell recordings from
      LA projection neurons in coronal mouse brain slices, we found that DA strongly
      increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs).
      In addition, DA application induced low-frequency (2-6 Hz) oscillatory activity
      of inhibitory circuits in the absence of excitatory input. The increase in sIPSC
      frequency required activation of D1-like receptors. Unlike D1 receptor-mediated
      transmission in other brain areas, this effect was independent of the cAMP/PKA
      signal transduction cascade, but involved activation of the protein tyrosine
      kinase Src. This indicates that DA orchestrates the activity of populations of
      interneurons in the LA by a D1-dependent, non-canonical signal transduction
      pathway.

PMID- 15458835
TI  - Age-dependence in the homeostatic upregulation of hippocampal dendritic spine
      number during blocked synaptic transmission.
AB  - Homeostatic regulation of spine number in mature hippocampal neurons results in
      more dendritic spines when synaptic transmission is blocked, providing a
      mechanism to compensate for diminished synaptic input. It is unsettled whether
      blockade of synaptic transmission also elevates spine number during development.
      To address this question, synaptic transmission was blocked in rat hippocampal
      slices during critical developmental stages of spine formation at postnatal days
      (P) 6-P22 and compared to adults. CA1 pyramidal cells were labeled with DiI and
      maintained for 5 h in one of three conditions, control artificial cerebrospinal
      fluid (ACSF), block media containing synaptic transmission antagonists in ACSF,
      or block media containing synaptic transmission antagonists in a nominally
      calcium-free ACSF with high magnesium. Slices were fixed in mixed aldehydes,
      sectioned, and the lateral dendrites were imaged in stratum radiatum with
      confocal microscopy. Dendritic spine density was quantified per unit length of
      dendrite. At P6-7 there were only a few protrusions emerging from the dendrites,
      which were predominantly filopodia-like in appearance. At both P11-12 and P15-16
      there was a mixture of dendritic spines and filopodia-like structures. By P20-22
      dendritic spines predominated and spine density was about 82% of the adult level.
      Dendritic spine density increased during blocked synaptic transmission at P20-22
      as in adults, but was unchanged during blockade at younger ages. When
      extracellular calcium was nominally zero, dendritic spine density further
      increased on P20-22 dendrites as in adults. In contrast, spine density decreased
      along P11-12 dendrites under the nominally zero calcium condition. Under control
      conditions, dendritic protrusions were longer at P6-7 than at all other ages,
      which did not differ from one another. When synaptic transmission was blocked,
      dendritic protrusions further elongated at P6-7 only. Under the nominally zero
      calcium condition with blocked synaptic transmission, dendritic protrusions
      shortened at P11-12 only. These findings reveal age-dependent changes in the
      manifestation of homeostatic control of dendritic spines that could be mediated
      by maturational changes in mechanisms regulating postsynaptic calcium.

PMID- 15458836
TI  - Enriched environment and acceleration of visual system development.
AB  - Rearing mice from birth in an enriched environment leads to a conspicuous
      acceleration of visual system development appreciable at behavioral,
      electrophysiological and molecular level. Little is known about the possible
      mechanisms of action through which enriched environment affects visual system
      development. It has been suggested that differences in maternal behavior between
      enriched and non-enriched conditions could contribute to the earliest effects of
      enriched environment on visual development and that neurotrophins, BDNF in
      particular, might be involved. Here, we examined Brain Derived Neurotrophic
      Factor (BDNF) levels in the visual cortex during development and showed that an
      increase occurs in the first week of life in enriched pups compared to standard
      reared pups; BDNF levels at birth were equal in the two groups. This suggests a
      postnatal rather than a prenatal effect of environment on BDNF. A detailed
      analysis of maternal care behavior showed that pups raised in a condition of
      social and physical enrichment experienced higher levels of licking behavior and
      physical contact compared to standard reared pups and that enhanced levels of
      licking were also provided to pups in an enriched environment where no adult
      females other than the mother were present. Thus, different levels of maternal
      care in different environmental conditions could act as indirect mediator for the
      earliest effects of enrichment on visual system development. Some of the effects
      of different levels of maternal care on the offspring behavior are long lasting.
      We measured the visual acuity of differentially reared mice at the end of the
      period of visual acuity development (postnatal day 45) and at 12 months of age,
      using a behavioral discrimination task. We found better learning abilities and
      higher visual acuity in enriched compared to standard reared mice at both ages.

PMID- 15458837
TI  - An imaging-based approach to identify ligands for olfactory receptors.
AB  - Odorant receptors (ORs) form one of the largest gene families in the genome.
      However, the vast majority are orphan receptors as the ligands that activate them
      remain unknown. Deorphaning approaches have generally focused on finding ligands
      for particular receptors expressed in homologous or heterologous cells; these
      attempts have met with only partial success. Here, we outline a conceptually
      different strategy in which we search for odorant receptors activated by a known
      odorant. Intrinsic signal imaging of the main olfactory bulb is first used to
      locate activated glomeruli in vivo, followed by retrograde tracing to label the
      sensory neurons in the olfactory epithelium projecting to the activated
      glomerulus. Subsequently, single cell RT-PCR is used to reveal the identity of
      the odorant receptors expressed in retrogradely labeled neurons. To demonstrate
      the applicability of this method, we searched for candidate ORs responding to the
      aldehyde odorant butanal. This method may be a useful tool to decipher specific
      ligand--OR interactions in the mouse olfactory bulb.

PMID- 15458838
TI  - Influx of extracellular calcium regulates actin-dependent morphological
      plasticity in dendritic spines.
AB  - Dendritic spines contain a specialized cytoskeleton composed of dynamic actin
      filaments capable of producing rapid changes in their motility and morphology.
      Transient changes in Ca2+ levels in the spine cytoplasm have been associated with
      the modulation of these effects in a variety of ways. To characterize the
      contribution of Ca2+ fluxes originating through different pathways to these
      phenomena, we used time-lapse imaging of cultured hippocampal neurons expressing
      GFP-actin to follow the influence of postsynaptic neurotransmitter receptors,
      voltage-activated Ca2+ channels and release from internal Ca2+ stores on spine
      actin dynamics. Stimulation of AMPA receptors produced a rapid blockade of actin
      dependent spine motility that was immediately reversible when AMPA was removed.
      Stimulation of NMDA receptors also blocked spine motility but in this case
      suppression of actin dynamics was delayed by up to 30 min depending on NMDA
      concentration and motility was never seen to recover when NMDA was removed. These
      effects could be mimicked by depolarizing neurons under appropriate circumstances
      demonstrating the involvement of voltage-activated Ca2+ channels in AMPA receptor
      mediated effects and the receptor associated Ca2+ channel in the effects of NMDA.
      Caffeine, an agent that releases Ca2+ from internal stores, had no immediate
      effect on spine actin, a result compatible with the lack of caffeine-releasable
      Ca2+ in cultured hippocampal neurons under resting conditions. Blocking internal
      store function by thapsigargin led to a delayed suppression of spine actin
      dynamics that was dependent on extracellular Ca2+. Together these results
      indicate the common involvement of changes in Ca2+ levels in modulating actin
      dependent effects on dendritic spine motility and morphology through several
      modes of electrophysiological activation.

PMID- 15458839
TI  - Distribution of the microtubule-related protein ninein in developing neurons.
AB  - Ninein associates with the centrosome in many cell types, where it recaptures
      minus-ends of microtubules after their release. In more complex and polarized
      cells, ninein has also been observed at noncentrosomal locales, where its
      function is not as well understood. We have found that cultured neurons contain
      both centrosomal and noncentrosomal ninein, and that the noncentrosomal ninein,
      typically observed as small particles, is both abundant and widespread.
      Noncentrosomal ninein is also dispersed throughout the cytoplasm of non-neuronal
      cells present within the cultures, but is particularly rich in the cytoplasm of
      neurons, where it may compete with centrosomal ninein to impede the recapture of
      microtubules by the centrosome after their release. Interestingly, noncentrosomal
      ninein is concentrated in regions of both neurons and non-neuronal cells
      undergoing retraction, such as in the trailing processes that retract during
      neuronal migration. These results suggest that noncentrosomal ninein may
      contribute to the configuration of the microtubule array underlying alterations
      in cellular morphology, and that such a contribution is likely to be particularly
      important for neuronal cells.

PMID- 15458840
TI  - Modification of the tropomyosin isoform composition of actin filaments in the
      brain by deletion of an alternatively spliced exon.
AB  - Tropomyosin (Tm) in non-muscle cells is involved in stabilisation of the actin
      cytoskeleton. Some of the 40 isoforms described are found in the brain and
      exhibit spatial and developmental regulation. Non-muscle isoforms from the gamma
      Tm gene can be subdivided into three subsets of isoforms differing at the C
      terminus, all of which are found throughout the brain and some of which are
      implicated in different aspects of neuronal function. We have approached the role
      of different gamma isoforms in neuronal function by knocking out a subset of
      isoforms. We show here that we can successfully knock out all isoforms containing
      the brain-specific 9c C-terminus. Brains from these mice did not show any gross
      abnormalities. Western analysis of adult brains showed that 9c isoforms are
      reduced in +/- and absent in -/- mice but that a compensation by 9a-containing
      isoforms resulted in total levels of gamma products remaining the same. No other
      Tm isoforms were altered. We have therefore specifically altered the Tm
      composition in these neurons which allows us to study the effects of these
      changes on the cytoskeleton of neurons during growth, differentiation and
      maturation and give us insights into the normal roles of these isoforms.

PMID- 15458841
TI  - Maturation of glutamatergic and GABAergic synapse composition in hippocampal
      neurons.
AB  - It is commonly accepted that glutamatergic and GABAergic presynaptic terminals
      form perfectly matched appositions opposite their appropriate receptors and
      associated binding proteins. However, recent reports indicate that certain
      synaptic proteins that are commonly used to identify excitatory or inhibitory
      synapses can be mismatched, particularly during development. In order to
      construct a more comprehensive scheme of synapse composition during development,
      we co-immunolabeled for several principle excitatory and inhibitory proteins over
      the course of synaptogenesis in cultured hippocampal neurons. We find that
      although the majority of synaptic appositions are composed of matched clusters of
      pre- and postsynaptic proteins appropriate for a particular neurotransmitter,
      many are initially mismatched, even in dendrites receiving both glutamatergic and
      GABAergic innervation. Over time, the fidelity of GABAergic synapse composition
      increases such that, despite the persistence of some mismatched components at
      glutamatergic sites, the incidence of mismatch diminishes at both inhibitory and
      excitatory synapses. Activation of either GABA-A or NMDA receptors promotes
      fidelity at GABAergic sites, but NMDA receptor activation promotes mismatching
      among glutamatergic synapses. Thus, apposition of pre- and postsynaptic elements
      can occur independent of neurotransmitter specificity and synaptic activity
      modifies these associations. Our findings support the idea that synapse
      maturation occurs in several distinct stages, and that these stages are regulated
      by a combination of activity-dependent and -independent factors.

PMID- 15458842
TI  - Cathepsin B-like proteolysis and MARCKS degradation in sub-lethal NMDA-induced
      collapse of dendritic spines.
AB  - Sub-lethal excitotoxic injury to dendrites can elicit loss or shrinkage of
      dendritic spines. Here, we used a cell culture model of sub-lethal NMDA-induced
      injury to investigate a role for proteolysis in spine collapse. Transient
      incubation with NMDA-induced spine collapse and spine F-actin loss within 10 min,
      an effect not mimicked by the actin assembly inhibitor latrunculin A. NMDA
      induced spine collapse was significantly attenuated by preincubation with broad
      spectrum cysteine protease inhibitors. Results obtained using several class
      specific protease inhibitors suggested that this protective effect was due to
      specific blockade of cathepsin B/L type protease activity, since selective
      inhibitors of only these proteases significantly attenuated spine loss. Cathepsin
      B-like immunoreactivity was observed at synaptic sites, but lysosomes were not.
      Immunoblot analysis showed that MARCKS (myristoylated-alanine-rich C-kinase
      substrate), a known substrate of cathepsin B, was specifically degraded in
      response to intense NMDA receptor stimulation. This effect was blocked by
      preincubation with a cathepsin B-selective inhibitor. Together these data suggest
      a model in which NMDA-induced spine collapse involves cathepsin B-like
      proteolysis of MARCKS, and possibly other proteins that regulate the actin-based
      cytoskeleton.

PMID- 15458843
TI  - Mobilization and fusion of a non-recycling pool of synaptic vesicles under
      conditions of endocytic blockade.
AB  - At vertebrate central synapses, it has been demonstrated that a resting pool of
      synaptic vesicles (SVs) exists that normally does not participate in SV release
      and recycling. It remains unclear whether SVs within the resting pool are capable
      of mobilization and fusion. Here, we combine live imaging of SV exo- and
      endocytosis using pH-sensitive GFP (synapto-pHluorins) with pharmacological and
      genetic manipulations of the SV cycle at the Drosophila NMJ. We demonstrate that
      a resting pool of SVs exists at this synapse that encompasses 30-41% of the total
      SV pool. Under conditions of endocytic blockade, using a temperature-sensitive
      dynamin mutation, the resting pool of SVs can be mobilized and released. We
      present a model for the presence of a resting pool of SVs that does not require
      molecular specification of a subpopulation of SVs.

PMID- 15458844
TI  - The complexity of PDZ domain-mediated interactions at glutamatergic synapses: a
      case study on neuroligin.
AB  - The postsynaptic specialisation at glutamatergic synapses is composed of a
      network of proteins located within the membrane and the underlying postsynaptic
      density. The strong interconnectivity between the protein components is mediated
      by a limited number of interaction modes. Particularly abundant are PDZ domain
      mediated interactions. An obstacle in understanding the fidelity of postsynaptic
      processes involving PDZ domains is the high degree of overlap with respect to
      their binding specificities. Focussing on transsynaptic adhesion molecules, we
      used the yeast two-hybrid system to obtain an overview of the binding
      specificities of selected C-terminal PDZ binding motifs. Neuroligin, a
      postsynaptic cell surface protein that spans the synaptic cleft and interacts
      with beta-neurexin, served as a starting point. Neuroligin binds to the PDZ
      domain-containing proteins PSD95, SAP102, Chapsyn110, S-SCAM, Magi1 and 3, Shank1
      and 3, Pick1, GOPC, SPAR, Semcap3 and PDZ-RGS3. Next, we examined the
      relationship between neuroligin and synaptic cell adhesion molecules or glutamate
      receptor subunits with respect to PDZ-mediated interactions. We found a limited
      overlap in the PDZ-domain binding specificities of neuroligin with those of
      Sidekick2 and Ephrin-B2. In contrast, Syndecan2 and IgSF4 show no overlap with
      the PDZ-domain specificity of neuroligin, instead, they bind to GRIP and
      syntenin. The AMPA receptor subunit GluR2 interacts with Semcap3 and PDZ-RGS3,
      whereas the kainate receptor subunits GluR5 and GluR6 show weak interactions with
      PSD95. In summary, we can sketch a complex pattern of overlap in the binding
      specificities of synaptic cell surface proteins towards PDZ-domain proteins.

PMID- 15458845
TI  - The dynamic turnover and functional roles of alpha-actinin in dendritic spines.
AB  - Excitatory synapses are located on actin-rich protrusions known as dendritic
      spines. alpha-Actinin is an actin binding protein enriched in the postsynaptic
      density (PSD) of excitatory synapses. Because it also binds to NMDA receptors and
      other PSD components, alpha-actinin has been proposed to link NMDA receptors and
      the PSD to the underlying actin cytoskeleton of the dendritic spine. Although
      alpha-actinin has been implicated in modulation of NMDA receptor activity, the
      cell biological function of alpha-actinin in neurons is unknown. We report here
      that alpha-actinin is concentrated in spines. Both the actin binding domain and
      the spectrin repeat region (which interacts with NMDA receptors) of alpha
      actinin2 are required for spine targeting. In live imaging experiments, Venus
      tagged alpha-actinin2 in dendritic spines showed faster turnover than PSD-95, as
      determined by fluorescent recovery after photobleaching (FRAP), and individual
      spines often showed marked fluctuations in alpha-actinin content over a time
      scale of minutes. Overexpression of alpha-actinin2 increased the length and
      density of dendritic protrusions in cultured hippocampal neurons, an effect that
      requires the actin binding domain and the spectrin repeats of alpha-actinin.
      These results suggest that alpha-actinin regulates spine morphology and density.

PMID- 15458846
TI  - Regulation of ADF/cofilin phosphorylation and synaptic function by LIM-kinase.
AB  - To investigate the role of the LIM-kinase (LIMK) family in the regulation of
      ADF/cofilin phosphorylation and synaptic function in the mammalian central
      nervous system (CNS), we conducted biochemical and electrophysiological analysis
      using mice that were genetically altered in the expression of LIMK-1 and LIMK-2.
      We showed here that while LIMK-2 knockout mice exhibited minimal abnormalities,
      the LIMK-1/2 double knockout mice were more severely impaired in both ADF/cofilin
      phosphorylation and excitatory synaptic function in the CA1 region of the
      hippocampus. These results indicate a critical role for the LIMK family in the
      regulation of ADF/cofilin and synaptic function in the brain.

PMID- 15458847
TI  - A proteasome-sensitive connection between PSD-95 and GluR1 endocytosis.
AB  - Synaptic transmission at excitatory synapses can be regulated by changing the
      number of synaptic glutamate receptors (GluRs) through endocytosis and
      exocytosis. The endocytosis of GluRs has recently been shown to require the
      activity of the ubiquitin-proteasome system (UPS): proteasome inhibitors or
      dominant negative forms of ubiquitin block the ligand-stimulated internalization
      of GluRs. We have examined whether PSD-95 is a potential target of the UPS.
      Following neurotransmitter stimulation, PSD-95 levels are negatively correlated
      with the magnitude of internalized GluR1 in individual neurons. Neurotransmitter
      stimulation also results in a proteasome-dependent decrease in dendritic PSD-95.
      Consistent with the idea that PSD-95 degradation is important for GluR
      internalization, overexpression of PSD-95 can inhibit neurotransmitter-stimulated
      GluR1 endocytosis. If PSD-95 is a direct target for proteasomal degradation, then
      the polyubiquitination of PSD-95 is expected. Using experimental conditions that
      favor the detection of polyubiquitination, however, no ubiquitination of PSD-95
      was detected. It is possible that the polyubiquitination of PSD-95 is short-lived
      and thus difficult to detect. Alternatively, the regulation of PSD-95 levels by
      the proteasome important for ligand-stimulated GluR endocytosis may be
      accomplished via an intermediate protein.

PMID- 15458848
TI  - Modulation of dopamine mediated phosphorylation of AMPA receptors by PSD-95 and
      AKAP79/150.
AB  - Communication between dopaminergic and glutamatergic synapses is critical for
      several functions related to cognition and emotion. Here, we examined whether
      dopamine receptor activity regulates phosphorylation and trafficking of the alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit,
      GluR1. We find treatment with a dopamine D1 receptor agonist enhanced GluR1
      phosphorylation at Ser845, the PKA phosphorylation site, in both striatal and
      prefrontal cortical neurons. Enhanced phosphorylation of GluR1 also correlated
      with increased amounts of GluR1 on the cell surface. These effects were disrupted
      by expression of mutant forms of the A-kinase anchoring protein (AKAP79/150) and
      the postsynaptic density protein, PSD-95, that fail to target synaptic sites.
      Similar enhancement of the phosphorylation of GluR1 was observed in the nucleus
      accumbens upon stimulation of dopamine release in vivo using electrical
      stimulation of dopamine cell bodies in the ventral tegmental area. These results
      suggest in vivo stimulation of dopamine release directly influences AMPA receptor
      phosphorylation and together with in vitro data indicate that coupling of the
      AMPA receptor to AKAP79/150 and PSD-95 modulate this process.

PMID- 15458849
TI  - Multiple functions for the cadherin/catenin complex during neuronal development.
AB  - The cadherin/catenin complex is a major transmembrane signaling complex through
      which extracellular signals can influence the cytoskeleton. It is present in
      neuronal processes during early development (J. Neurosci. 18 (1998) 6892) and
      appears to play multiple roles during neural circuit formation and maturation
      (Nat. Neurosci. 7 (2004) 357; Neuron 35 (2002) 77; Nat. Neurosci. 6 (2003) 1169).
      In previous work (Nat. Neurosci. 6 (2003) 1169), we showed that molecular
      manipulation of the cadherin/catenin complex has significant effects on the
      dendritic aborization of cultured hippocampal neurons at 9 days in vitro
      (d.i.v.). Here we extend these observations by examining the effects of over
      expression of beta-catenin (fused to GFP; GFP-beta-cat(*)) or sequestering
      endogenous beta-catenin [using the intracellular domain of N-cadherin;
      Ncad(intra)] in cultured hippocampal neurons at different developmental stages.
      When transfected at 1 d.i.v. and assayed 48 h later, over-expression of GFP-beta
      cat(*) increased axonal length and complexity, while sequestering endogenous beta
      catenin had the opposite effect. Dendritic aborization was also enhanced by GFP
      beta-cat(*) expression throughout early development although the magnitude of
      this effect decreased as neurons matured from 3 to 12 d.i.v. Finally, at 12
      d.i.v., GFP-beta-cat(*) expression increased the density of dendritic spines
      although not the relative proportion of different subtypes of spines. These
      results demonstrate that the cadherin/catenin complex plays multiple roles in the
      development of neuronal morphology and that these roles change as neurons mature.

PMID- 15458850
TI  - Cortisol responses to combined dexamethasone/CRH test in outpatients with a major
      depressive episode.
AB  - The DEX/CRH test is now a well established method to test the hypothalamic
      pituitary-adrenal (HPA) axis for depressed patients in an inpatient setting. The
      aim of this study was to evaluate this test in an outpatient population suffering
      from major depression compared to a healthy control group. The main result is a
      statistically significant difference concerning the delta value for cortisol
      plasma value on the DEX/CRH test for depressed patients with two or more previous
      episodes compared to healthy controls. On the contrary, the difference was not
      statistically significant for patients with only one or no previous episodes. In
      future studies, it could be interesting to use this test more specifically by
      dividing ambulatory patients into subgroups according to their past depressive
      history. It could also be interesting to measure the ACTH level.

PMID- 15458851
TI  - Increased diurnal salivary cortisol in women with borderline personality
      disorder.
AB  - Borderline personality disorder (BPD) is characterized by a pervasive pattern of
      instability in affect regulation, impulse control, interpersonal relationships,
      and self-image. In previous studies, we have used portable mini-computers to
      assess the severity of recurrent states of aversive emotional distress and
      dissociation during ambulatory conditions. Here, we used this approach for the
      assessment of the hypothalamic-pituitary-adrenal (HPA) axis in patients with BPD.
      We studied 23 unmedicated female patients with BPD and 24 matched healthy
      controls. Salivary cortisol was collected from all participants during ambulatory
      conditions in response to reminders provided by portable mini-computers on 3
      consecutive days every 2 h for 14 h after awakening. In addition, cortisol in
      response to awakening was determined in four 15 min intervals on days 1 and 2.
      After the last collection of cortisol on the second day, 0.5 mg dexamethasone was
      administered in order to achieve cortisol suppression on day 3 (low-dose
      dexamethasone suppression test, DST). Patients with BPD displayed significantly
      higher salivary cortisol levels than healthy controls as demonstrated by higher
      total cortisol in response to awakening and higher total daily cortisol levels.
      There were significantly more non-suppressors of cortisol in the low-dose DST in
      the patient group when compared to the control group. The ambulatory assessment
      of saliva cortisol is a suitable approach to study basic parameters of the HPA
      axis in patients with BPD. Increased adrenal activity and lowered feedback
      sensitivity of the HPA-axis may characterise BPD. Further studies have to reveal
      reasons of heightened adrenal activity in these patients.

PMID- 15458852
TI  - Executive functions and updating of the contents of working memory in unipolar
      depression.
AB  - BACKGROUND: Depression is characterized by cognitive impairments, including
      executive dysfunctions. These executive deficits could reflect impairments of
      more basic executive processes, such as updating, set shifting and inhibition.
      While shifting and inhibition impairments are often reported, studies on
      depression have been somewhat obscure about specific deficits of the updating
      process. The main goal of that study was to assess the updating process in young
      in-patients with depression. METHODS: We used a verbal n-back task to assess
      updating process. Load and mental manipulation within working memory (WM) were
      incremented by using three different levels of complexity (1,2,3-back).
      Neuropsychological tests and an attentional task (0-back) were also administered
      to subjects. Twenty-two individuals meeting DSM-IV criteria for Major Unipolar
      Depression and 22 healthy control subjects, matched on age, verbal IQ and
      education, were included in the study. RESULTS: Subjects with depression showed
      significant deficits at the n-back task compared to control subjects. They were
      normal in tasks assessing the short-term maintenance in WM and attention. This
      suggests that depressed patients exhibit impairment in the updating process.
      Depressed patients also showed set shifting and inhibition deficits. Only the n
      back task was correlated with the number of hospitalizations and the longitudinal
      course of the illness. CONCLUSIONS: Our results suggest that young depressed in
      patients have widespread executive dysfunctions, including updating, shifting and
      inhibition processes. We also found a correlation between a longitudinal measure
      of depression severity and an updating task performance. We suggest that using
      multiple executive tasks gives the opportunity to distinguish the specific
      influence of various executive processes on clinical dimensions in depression.

PMID- 15458853
TI  - Derivation of a definition of remission on the Montgomery-Asberg depression
      rating scale corresponding to the definition of remission on the Hamilton rating
      scale for depression.
AB  - During the past decade the Montgomery-Asberg Depression Rating Scale (MADRS) has
      been used with increasing frequency to measure outcome in antidepressant efficacy
      trials (AETs). In characterizing treatment outcome in AETs it is common to define
      treatment remission as a score below a predetermined cutoff score on the scale.
      Various cutoffs have been used to define remission on the MADRS. The goal of the
      present paper is to determine the cutoff on the MADRS that most closely
      corresponds to the cutoff most frequently used on the Hamilton Rating Scale for
      Depression to define remission. Three hundred and three psychiatric outpatients
      who were being treated for a DSM-IV major depressive episode were rated on the
      HRSD and the MADRS. A linear regression equation was computed to estimate MADRS
      scores from HRSD scores. After deriving the regression equation, we computed the
      MADRS score corresponding to an HRSD score of 7. We also examined the
      sensitivity, specificity and overall classification rate of the MADRS for
      identifying remission on the HRSD. Based on the equation from a linear regression
      analysis for the entire sample, a MADRS score of </=11 would correspond to a
      score of </=7 on the HRSD. We repeated the analysis after excluding the more
      severely depressed patients who currently met criteria for MDD, and based on the
      equation from this regression analysis a MADRS score of </=10 would correspond to
      a score of </=7 on the HRSD. In a complementary analysis, we examined the
      sensitivity, specificity and overall classification rate of the MADRS at
      different cutoff points for identifying remission, and found that a cutoff of
      </=10 maximized the level of agreement with the HRSD definition of remission. In
      conclusion, the regression equation relating HRSD and MADRS scores is dependent,
      in part, on the range and severity of scores in the sample. To facilitate
      comparisons of studies using the HRSD and MADRS our results suggest that a cutoff
      of 10 on the MADRS is equivalent to the HRSD cutoff of 7.

PMID- 15458854
TI  - Suicide risk management for the sequenced treatment alternatives to relieve
      depression study: applied NIMH guidelines.
AB  - NIMH guidelines to manage subjects who are suicidal during their participation in
      clinical trials include a full range of procedures to minimize suicidal risk, yet
      no reports to date have shown how researchers should best implement these
      guidelines. The architects of the sequenced treatment alternatives to relieve
      depression (STAR*D) study operationalized and implemented the NIMH guidelines by
      developing a comprehensive set of procedures to detect, monitor, and manage
      suicidal subjects during a large, complex, multisite clinical trial. Because of
      the large size of the study (anticipated n = 4000), the wide geographic
      distribution, the large number of treating STAR*D clinicians, the broad array of
      subjects with psychiatric and medical comorbidities, and the focus on treatment
      resistant depression, along with the complexity of multiple treatment steps and
      randomization points in STAR*D, the risk of suicide, safety monitoring of
      suicidal subjects presented a unique challenge. This paper describes methods
      derived from the NIMH guidelines used to manage suicidal risk in STAR*D including
      the use of an interactive voice response system to alert clinicians, regional
      center directors, and safety officers.

PMID- 15458855
TI  - Impairment of visuospatial memory is associated with decreased slow wave sleep in
      schizophrenia.
AB  - Cognitive impairments such as memory deficits and sleep disturbances are common
      clinical features of schizophrenia. Since sleep plays an important role in
      consolidation of memory, we hypothesize, that there is an interrelationship
      between distinct alterations in sleep and memory performance in schizophrenia. We
      studied 17 patients with schizophrenia on stable antipsychotic medication with
      amisulpride (age range 22-44 years; 7 women) and 17 healthy controls (matched for
      age, gender and educational level). Sleep was recorded and scored according to
      the standard criteria by Rechtschaffen and Kales. Immediately before
      polysomnography and the morning after we performed neuropsychological tasks
      including Rey-Osterrieth Complex Figure Test and a test for recall of spatial
      location for testing aspects of declarative memory and a mirror tracing skill for
      procedural memory. In comparison to healthy controls, the patients showed a
      significant increase in sleep onset latency and a significant decrease in sleep
      efficiency and amount of slow wave sleep (SWS). Furthermore, the patients'
      performance in recall of the Rey-figure and of spatial location the next morning
      was significantly impaired. These impairments in the tests for visuospatial
      memory were positively correlated with reduction in the amount of SWS and in
      sleep efficiency. These results point to a functional interrelationship between
      regulation of SWS and performance in visuospatial memory in schizophrenia. If
      these results of our pilot study hold true, they will allow the development of
      innovative treatment strategies for neuropsychological deficits in patients with
      schizophrenia.

PMID- 15458856
TI  - Secondary verbal memory: a potential endophenotype of schizophrenia.
AB  - This study aimed at identifying neuropsychological endophenotypes of
      schizophrenia which met the criteria of stability and sensitivity. Twenty-six non
      schizophrenic first-degree relatives together with their affected family members
      (all simplex-families) underwent assessment with a comprehensive
      neuropsychological test battery both at baseline and 13 months follow-up. Follow
      up patients were in a state of stable remission. Further, 21 unrelated,
      demographically balanced, non-vulnerable controls were tested one at a time. A
      principal components analysis of our test battery resulted in four factors: (1)
      Vigilance, attention, and psychomotor, (2) secondary verbal memory, (3) immediate
      and working memory, and (3) abstraction and problem solving. At baseline testing
      our study revealed a pattern of selective cognitive deficits in the relative
      group that is less pronounced, yet qualitatively similar, to that found in the
      patient sample. The most severe deficits displayed both the patients and their
      relatives in the secondary verbal memory domain. The dysfunctions in secondary
      verbal memory at baseline testing significantly correlated with negative symptoms
      only. Secondary verbal memory deficits proved to be relatively independent of age
      at onset of illness, illness duration, and neuroleptic dosage. Longitudinally,
      dysfunctions in the patients' secondary verbal memory fluctuated over time and
      with negative symptoms, and persisted in remitted patients at the same level as
      in their relatives. In conclusion, the secondary verbal memory met the criteria
      of relative stability and sensitivity in our sample of simplex-families. Thus,
      the secondary verbal memory seems to be a potential endophenotypic marker of
      schizophrenia, even for cases with a hypothetically lower genetic loading.

PMID- 15458857
TI  - Does urbanicity shift the population expression of psychosis?
AB  - Growing up in an urban area has been shown to be associated with an increased
      risk of psychotic disorder in later life. While it is commonly held that a only a
      tiny fraction of exposed individuals will develop schizophrenia, recent evidence
      suggests that expression of psychosis in exposed individuals may be much more
      common, albeit at attenuated levels. Findings are based on a population sample of
      2548 adolescents and young adults aged originally 14-24 years, and followed up
      over almost 5 years up to ages 17-28 years. Trained psychologists assessed all
      these subjects with the core psychosis sections on delusions and hallucinations
      of the Munich-Composite International Diagnostic Interview. Growing up in an
      urban area was associated with an increased risk of expression of psychosis in
      the adolescents and young adults (adjusted OR 1.31, 95% CI 1.03-1.66). The proxy
      environmental risk factor that urbanicity represents may shift a relatively large
      section of the adolescent population along a continuum of expression of
      psychosis. Other causal influences may be required to make the transition to
      schizophrenia in adult life.

PMID- 15458858
TI  - Substantial decrease of psychiatric comorbidity in chronic alcoholics upon
      integrated outpatient treatment - results of a prospective study.
AB  - It is far from clear how comorbidity changes during alcoholism treatment. This
      study investigates: (1) the course of comorbid Axis I disorders in chronic
      alcoholics over 2 years of controlled abstinence in the outpatient long-term
      intensive therapy for alcoholics (OLITA) and (2) the effect of comorbid Axis I
      and II disorders in this group of patients on subsequent drinking outcome over a
      four-year follow-up. This prospective treatment study evaluates psychiatric
      variables of 89 severely affected chronic alcohol dependent patients on admission
      (t(1)), month 6 (t(2)), 12 (t(3)) and 24 (t(4)). Drinking outcomes have been
      analyzed from 1998 to 2002. On admission, 61.8% of the patients met criteria for
      a comorbid Axis I disorder, 63.2% for a comorbid personality disorder. Axis I
      disorders remit from t(1) (59.0% ill), t(2) (38.5%), t(3) (28.2%) to t(4) (12.8%)
      (p < 0.0001). Anxiety disorders remit more slowly from t(1) (43.6%) to t(3)
      (20.5%, p = 0.0086), whereas mood disorders remit early between t(1) (23.1%) and
      t(2) (5.1%, p = 0.0387) with a slight transient increase at t(3) (10.3%). During
      the four-year follow-up, the cumulative probability of not having relapsed
      amounts to 0.59. Two predictors have a strong negative impact on abstinence
      probability: number of inpatient detoxifications (p = 0.0013) and personality
      disorders (p = 0.0106). The present study demonstrates a striking remission of
      comorbid Axis I disorders upon abstinence during comprehensive long-term
      outpatient alcoholism treatment. The presence of an Axis II rather than an Axis I
      disorder on admission strongly predicts drinking outcome over a four-year follow
      up.

PMID- 15458859
TI  - Subthalamic nucleus stimulation and the development of delusion.

PMID- 15458867
TI  - Keynote lecture from the EACE annual meeting 2002: an analytical view of cancer
      education.

PMID- 15458868
TI  - Integration of a problem-based multidisciplinary clinical cancer management
      course into undergraduate education.
AB  - BACKGROUND: Undergraduate cancer education programs usually involve diagnosis and
      treatment of various organs and tissues of the body that are invaded by this
      disease. Teaching organ system-based oncology by different disciplines causes a
      fragmented structure of knowledge with difficulty on reuniting the knowledge for
      the real patient. METHODS: Along with the reorganization process of the
      curriculum, an integrated, problem-based multidisciplinary clinical cancer
      management course has been introduced to fifth-year students. The course has
      consisted of group studies, panel discussions, site visits to departments
      involved in diagnosis and treatment of cancer, and lecture tutorials enriched
      with interactive learning methods. RESULTS AND CONCLUSION: Overall assessment of
      the course has been encouraging in terms of a clinical approach for students to
      the cancer patient, and innovations for better learning have been implemented for
      the following year.

PMID- 15458869
TI  - Evaluation of the OncoTCap (Oncology Thinking Cap) simulation in teaching medical
      students about clinical trials: some successes and some surprises.
AB  - OBJECTIVE: A training workshop for cancer clinical trials was developed utilizing
      a computer simulation encompassing cancer biology, metabolism, adverse effects,
      and clinical trial design. METHOD: Fourth-year medical students in a neoplasia
      elective course participated. The workshop was structured to maximize group
      discussions and interactions. Pretests and posttests were administered in a
      crossover design to evaluate learning about cancer clinical trials. Results. The
      comparison showed that the workshop did impart knowledge about cancer clinical
      trials. CONCLUSIONS: Student evaluations of the workshop showed slight
      improvements from the first year to the second year.

PMID- 15458870
TI  - Evaluating curriculum changes in undergraduate cancer education.
AB  - BACKGROUND: Previous studies have indicated that Australian medical schools have
      not adequately prepared our graduating doctors to care for patients with cancer.
      The University of Western Australia (UWA) introduced a two-week clinical
      attachment in cancer medicine for fifth-year students in 2000 and a four-day
      clinical attachment in palliative care for sixth-year students in 2001. This
      article evaluates the introduction of these dedicated clinical attachments in
      cancer and palliative care. METHOD: The Australian Cancer Society's Cancer
      Education Survey was administered to the UWA graduates starting their intern year
      in teaching hospitals in Perth, Western Australia, in 2002. Their responses were
      compared with data collected in a similar national survey of Australian and New
      Zealand interns in 2001. RESULTS: The response rate was 56% (n = 70). When
      compared with the national data for 2001, more UWA interns (2002) would refer a
      newly diagnosed breast cancer patient to a multidisciplinary breast clinic (97%
      vs. 74%, P < .001). Fewer UWA 2002 interns rated their training as "poor or very
      poor" in the management of patients with incurable cancer (19% vs. 35%, P = .008)
      and the management of symptoms in patients dying from cancer (10% vs. 37%, P <
      .001), but they were more likely to rate their training in assisting a patient to
      stop smoking as "poor or very poor" (54% vs. 21%, P < .001). Only a quarter of
      the UWA 2002 interns had examined a patient with a cancer of the mouth or tongue
      (25% vs. 49%, P < .001), and only two thirds had examined a patient with lymphoma
      (64% vs. 83%, P < .001). CONCLUSIONS: Our data reflect changes in the final two
      years of the medical course at UWA and suggest that the introduction of dedicated
      attachments in cancer and palliative care has better prepared graduating doctors
      to care for patients with cancer.

PMID- 15458871
TI  - The evaluation of a two-day interdisciplinary continuing education event in
      psychosocial oncology.
AB  - BACKGROUND: The study evaluated the effectiveness of a two-day continuing
      education (CE) course developed to increase multidisciplinary oncology
      professionals' awareness of psychosocial issues and to equip them with the skills
      and knowledge necessary to identify psychosocial issues and intervene
      effectively. METHODS: Attendees (n = 120) were asked to complete a pre- and 6
      month postcourse questionnaire assessing psychosocial orientation using the
      Physician Belief Scale and the ability to identify psychosocial issues; they were
      also asked to suggest appropriate interventions based on five case vignettes.
      RESULTS: Sixty-nine (56%) participants returned the precourse questionnaire, and
      42 (35%) returned the postcourse questionnaire. Psychosocial orientation
      increased significantly from precourse to postcourse (P = .03). Based on the five
      case vignettes, participants were able to identify significantly more
      psychosocial issues (10.5 vs. 7.7, P = .005) and suggest more interventions (12.6
      vs. 8.7, P < .001) 6 months following the course. CONCLUSIONS: These findings
      support the effectiveness of a two-day CE course to improve oncology
      professionals' psychosocial orientation and ability to identify psychosocial
      issues and interventions.

PMID- 15458872
TI  - Rural cancer patients' perspectives on clinical trials: a qualitative study.
AB  - BACKGROUND: To increase the participation of low-income, rural cancer patients in
      clinical trials, a better understanding of patients' attitudes, knowledge, and
      beliefs is needed. METHODS: In-depth interviews were conducted with 17 cancer
      patients living in rural West Virginia. RESULTS: Patients had limited knowledge
      regarding clinical trials. Factors that might influence their decisions to
      participate include location of the treatment facility, physician recommendation,
      disease status, side effects of the treatment, and the perceived effectiveness of
      treatment. CONCLUSIONS: Rural, low-income cancer patients should be better
      informed about clinical trials, when applicable. Physician trust may enhance
      willingness to participate if clinical trials are close to home.

PMID- 15458873
TI  - Barriers to colorectal cancer screening: an educational diagnosis.
AB  - BACKGROUND: Colorectal cancer (CRC) is a largely preventable disease through
      early detection and treatment, yet screening rates remain low and mortality rates
      remain high, particularly among low-income, minority populations. This study was
      conducted to identify barriers to CRC screening. METHODS: Repeated telephone
      contacts were conducted with 226 individuals from 52 to 80 years of age, who had
      not recently received CRC screening. The contacts were intended to educate and
      encourage participants to obtain CRC screening. Within this context, CRC
      screening barriers were identified and categorized using an educational diagnosis
      as specified in the Precede-Proceed Framework. RESULTS: Findings showed that the
      most frequently observed barrier was lack of familiarity with CRC screening
      guidelines and tests. Availability and accessibility to screening tests was a
      barrier that was difficult to overcome for many participants. The majority of
      participants faced two or more barriers. CONCLUSIONS: This study suggests a need
      for public health education about CRC screening guidelines and tests and greater
      accessibility to CRC screening.

PMID- 15458874
TI  - Promoting informed decision making: evaluating a community-based prostate health
      awareness program.
AB  - BACKGROUND: For health educators, the controversy surrounding routine prostate
      cancer screening provides curriculum development and delivery challenges. The
      purpose of this study was to evaluate a community-based prostate health awareness
      program. METHODS: Using a pretest-posttest design, participants were recruited
      from community-based organizations to assess the effectiveness of the program in
      the areas of knowledge gain, short-term intentions, and changing prostate health
      behaviors. RESULTS: Many of the participants reported having been tested for
      prostate cancer, yet there was a lower than expected pretest knowledge base.
      There were significant increases in knowledge on the posttest and some impact on
      short-term intentions and behavior. DISCUSSION: A community-based prostate health
      awareness program prior to the patient-physician encounter can assist health-care
      professionals in the education process and give men the tools to make an informed
      decision.

PMID- 15458875
TI  - Psychosocial and medical predictors of colorectal cancer screening among low
      income medical outpatients.
AB  - BACKGROUND: Identification of factors related to colorectal cancer screening
      (CRC) and intent to obtain fecal occult blood tests (FOBTs) among low-income
      persons are important because CRC incidence and mortality are higher among
      socioeconomically disadvantaged populations. METHOD: Participants were 193
      individuals 50 years of age and older. CRC screening and intent to obtain FOBTs
      were dependent measures. Demographic variables, objective risk factors, and
      health beliefs were independent measures. RESULTS: Digital rectal examinations
      and FOBTs were obtained by 41% and 22%, respectively, during the previous year.
      Flexible sigmoidoscopies were obtained by only 19% of those 55 years of age and
      older during the previous five years. Multivariate analyses showed that family
      history of CRC, personal history of polyps, and physician recommendation were the
      strongest predictors of CRC screening. Family history of CRC and self-efficacy
      were related to intent to obtain FOBTs. CONCLUSIONS: Results suggest the
      importance of physician assessment of personal and family CRC risk factors, as
      well as recommendation of CRC screening, to all patients as part of routine
      medical care.

PMID- 15458876
TI  - Appreciative inquiry.

PMID- 15458880
TI  - The tolling of the bell: women's health, women's rights.

PMID- 15458881
TI  - Shoulder dystocia and flying airplanes!

PMID- 15458882
TI  - Sequential pathways of testing after first-trimester screening for trisomy 21.
AB  - OBJECTIVE: To evaluate the performance and use of second-trimester multiple
      marker maternal serum screening for trisomy 21 by women who had previously
      undergone first-trimester combined screening (nuchal translucency, pregnancy
      associated plasma protein A, and free beta-hCG), with disclosure of risk
      estimates. METHODS: In a multicenter, first-trimester screening study sponsored
      by the National Institute of Child Health and Human Development, multiple-marker
      maternal serum screening with alpha-fetoprotein, unconjugated estriol, and total
      hCG was performed in 4,145 (7 with trisomy 21) of 7,392 (9 with trisomy 21) women
      who were first-trimester screen-negative and 180 (7 with trisomy 21) of 813 (52
      with trisomy 21) who were first-trimester screen-positive. Second-trimester risks
      were calculated using multiples of the median and a standardized risk algorithm
      with a cutoff risk of 1:270. RESULTS: Among the first-trimester screen-negative
      cohort, 6 of 7 (86%) trisomy 21 cases were detected by second-trimester multiple
      marker maternal serum screening with a false-positive rate of 8.9%. Among the
      first-trimester screen-positive cohort, all 7 trisomy 21 cases were also detected
      in the second trimester, albeit with a 38.7% false-positive rate. CONCLUSION: Our
      data demonstrate that a sequential screening program that provides patients with
      first-trimester results and offers the option for early invasive testing or
      additional serum screening in the second trimester can detect 98% of trisomy 21
      affected pregnancies. However, such an approach will result in 17% of patients
      being considered at risk and, hence, potentially having an invasive test. LEVEL
      OF EVIDENCE: II-2

PMID- 15458883
TI  - Evaluation of residents' delivery notes after a simulated shoulder dystocia.
AB  - OBJECTIVE: To describe and analyze delivery notes after a shoulder dystocia drill
      with a birthing simulator METHODS: A total of 33 residents from 2 university
      training programs underwent testing on a standardized shoulder dystocia scenario
      with an obstetric birthing simulator. After the completion of the delivery, each
      resident was informed of the infant's Apgar scores and birth weight and told that
      the infant was moving all extremities. The resident was then given a blank
      progress note and asked to write a delivery note. The notes were evaluated for 15
      key components. RESULTS: Seventy-six percent (n = 25) of residents recorded less
      than 10 of 15 key components of a delivery note after a shoulder dystocia. The
      majority of residents (91%, 30/33) included the correct order of the maneuvers
      used during the delivery, but most did not note which shoulder was anterior (18%,
      6/33) or how long the head-to-body interval was during delivery (45%, 15/33).
      CONCLUSION: Residents' delivery notes after a shoulder dystocia simulation often
      lacked critical elements. Training in documentation is needed in residency
      training. The addition of the delivery note and feedback regarding the note
      represents a simple innovation in this teaching scenario that may help identify
      deficiencies in documentation. LEVEL OF EVIDENCE: III

PMID- 15458884
TI  - Gestational weight gain, macrosomia, and risk of cesarean birth in nondiabetic
      nulliparas.
AB  - OBJECTIVE: To examine how the association between excessive weight gain and
      cesarean birth is modified by infant birth weight in nondiabetic women. METHODS:
      We designed a retrospective cohort study of singleton, term, nulliparous women
      with cephalic presentations delivering at a single university hospital. Subjects
      with diabetes were excluded. Bivariate and multivariate analyses were performed.
      Regression models controlled for maternal age, maternal prepregnancy body mass
      index, gestational age, ethnicity, smoking, birth weight, and date of delivery.
      RESULTS: Women gaining above Institute of Medicine guidelines were more likely to
      have a cesarean birth, even if birth weight was less than 4,000 g. In the
      multivariate analysis, women with excessive weight gain had an odds ratio of 1.40
      (95% confidence interval 1.22-1.59) for cesarean birth. When absolute weight gain
      (total pregnancy weight gain minus birth weight and placental weight) was used in
      the multivariate analysis, excessive weight gain was still an independent
      predictor of cesarean delivery. Although macrosomia was a stronger predictor of
      cesarean than weight gain alone, excessive weight gain was much more common than
      macrosomia in our cohort. CONCLUSION: Excessive weight gain during pregnancy is
      an independent risk factor for cesarean birth, even when birth weight is not
      excessive. Other mechanisms besides macrosomia may be involved in the association
      between high weight gain and cesarean birth. We estimate that of the
      approximately 288,000 primary cesarean deliveries performed in nulliparas
      annually in the United States, 64,000 would be prevented if no women gained above
      Institute of Medicine recommendations. LEVEL OF EVIDENCE: II-2

PMID- 15458885
TI  - Mode of delivery and neonatal survival of infants with isolated gastroschisis.
AB  - OBJECTIVE: We sought to compare neonatal survival of infants with gastroschisis
      by mode of delivery. METHODS: We conducted a retrospective cohort study on
      infants with gastroschisis who were delivered in New York State from 1983 through
      1999. We compared neonatal mortality between infants born vaginally and those
      delivered by cesarean using adjusted hazard ratios derived from Cox proportional
      hazards regression models. RESULTS: A total of 354 infants were found to have
      isolated gastroschisis. Of these, 174 were delivered vaginally, whereas 180 were
      delivered by cesarean. Neonatal mortality was registered among 18 infants (5.1%);
      12 (6.9%) in the vaginal and 6 (3.3%) in the cesarean group. After controlling
      for potential confounders, the risk for neonatal demise was similar in both the
      vaginal and cesarean subcohorts (adjusted hazard ratio 0.84, 95% confidence
      interval [CI] 0.29-2.43). Preterm birth was the morbidity pathway that explained
      the early demise of infants with gastroschisis, irrespective of mode of delivery
      (adjusted hazard ratio 3.4, 95% CI 1.10-10.4) whereas small for gestational age
      did not predict mortality (adjusted hazard ratio 1.04, 95% CI 0.13-8.14).
      CONCLUSION: In this study the mode of delivery was not found to be associated
      with neonatal survival of infants with gastroschisis. Preterm birth rather than
      small for gestational age was the predictor of neonatal death among gastroschisis
      infants. LEVEL OF EVIDENCE: III

PMID- 15458886
TI  - Midline rectovaginal fascial plication for repair of rectocele and obstructed
      defecation.
AB  - OBJECTIVE: To estimate the efficacy of midline fascial plication of the posterior
      vaginal wall in women with rectoceles and obstructed defecation. METHODS:
      Prospective evaluation of 38 consecutive women with symptomatic rectoceles (stage
      II or greater) and obstructed defecation included pre- and postoperative
      standardized pelvic floor questions, pelvic organ prolapse quantification
      measurements, validated bowel function questionnaires, defecating proctogram, and
      patient satisfaction. Reviews were conducted by nonsurgical coauthors. RESULTS:
      The median follow-up was 12.5 months (range 2.5-26 months). The subjective
      success rates were 97% (95% confidence interval [CI] 0.83-1.00%) at 12 months and
      89% (95% CI 0.55-0.98%) at 24 months. The objective success rates were 87% (95%
      CI 0.64-0.96%) at 12 months and 79% (95% CI 0.51-0.92%) at 24 months. The average
      points, Ap and Bp, were significantly reduced from -0.1 (range -2 to 3) and 1.1
      (range -1 to 8), preoperatively, to -2.6 (range -3 to -1) and -2.5 (range -3 to
      0), postoperatively, respectively (P <.001). Depth of rectocele also reduced
      postoperatively on defecating fluoroscopy (P <.001). The correction of the
      anatomical defect was associated with improved functional outcome, with 33 women
      (87%) no longer experiencing obstructed defecation, and there was a significant
      reduction in postoperative straining to defecate, hard stools, and dyspareunia (P
      =.001). The improved anatomical and functional outcomes were reflected in the
      fact that 97% of the women reported very high patient satisfaction. CONCLUSION:
      Midline fascial plication is effective in correcting anatomical and functional
      outcomes associated with symptomatic rectoceles and obstructed defecation. LEVEL
      OF EVIDENCE: III

PMID- 15458887
TI  - Anal sphincter injury in women with pelvic floor disorders.
AB  - OBJECTIVE: 1) To estimate the rate of anal incontinence and anal sphincter injury
      in a group of women with pelvic floor disorders; 2) to evaluate the relationship
      between anal incontinence and anal sphincter injury as demonstrated by endoanal
      ultrasonography; 3) to explore any associations between operative vaginal
      delivery and anal sphincter injury in this population. METHODS: A cohort of 100
      women with stage II or greater pelvic organ prolapse and/or urinary incontinence
      completed the Rockwood-Thompson Fecal Incontinence Severity Index Questionnaire
      (FISI). Pelvic organ prolapse was recorded using the Pelvic Organ Prolapse
      Quantification system. Multichannel cystometry and endoanal ultrasonography were
      performed. Categorical data were compared using the chi(2) statistic. The FISI
      scores were correlated with degree of anal sphincter injury using the Pearson
      correlation coefficient (r). RESULTS: Fifteen women with pelvic organ prolapse
      only, 28 with urinary incontinence only, and 57 with both were evaluated. Mean
      age (+/- standard deviation) and body mass index were 57.1 +/- 13.2 years and
      29.8 +/- 6.8 kg/m(2), respectively. Median parity was 3. Fifty-four percent of
      those studied had anal incontinence, and 52% had anal sphincter defects. Anal
      incontinence was significantly associated with sphincter injury (odds ratio 36.4,
      95% confidence interval 12-114, P <.001). The FISI scores were positively
      correlated with increasing degrees of anal sphincter disruption (r = 0.81, P
      <.001). A history of operative vaginal delivery was significantly associated with
      anal sphincter injury (P =.023). CONCLUSION: Anal incontinence and anal sphincter
      injury are common in women with other pelvic floor disorders and are
      significantly related. Operative vaginal delivery may contribute to unrecognized
      anal sphincter trauma in this population. LEVEL OF EVIDENCE: III

PMID- 15458888
TI  - Narrow pubic arch and increased risk of failure for vaginal hysterectomy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the risk factors involved in
      failed vaginal hysterectomies. METHODS: Data on all vaginal hysterectomies
      performed by a single gynecologic surgeon were collected prospectively. Patients
      requiring pelvic floor repair were excluded. Any procedure converted to the
      abdominal approach was classified as a failed vaginal hysterectomy and comprised
      the study group. For every woman who had a failed vaginal hysterectomy, the next
      2 women who had successful vaginal hysterectomies immediately after the failed
      vaginal hysterectomy were taken as controls. Risk factors such as age, parity,
      body weight, surgical indication, uterine size, presence of leiomyomata in the
      anterior lower uterine segment, previous pelvic surgeries, abdominopelvic
      adhesions, location and length of cervix, narrow pubic arch, intraoperative
      complications such as bleeding requiring transfusion, visceral injury,
      nulliparity, and adnexal removal were compared between groups. RESULTS: We
      compared 25 failed vaginal hysterectomies with 50 controls whose procedures were
      completed successfully through the vagina. Among all the factors gynecologists
      can assess preoperatively, only the presence of a narrow pubic arch increased the
      risk of failure for vaginal hysterectomy (odds ratio [OR] 4.1; 95% confidence
      interval 1.32-12.69). Intraoperative bleeding with transfusion was also found as
      an independent cause for conversion to laparotomy (OR 7.37; 95% confidence
      interval 1.75-31.06). CONCLUSION: Women with a narrow pubic arch are not good
      candidates for vaginal hysterectomy. The most common unpredictable cause for
      conversion to laparotomy from the vaginal approach is intraoperative bleeding
      requiring transfusion. LEVEL OF EVIDENCE: II-2

PMID- 15458889
TI  - Quality of life and sexual function after hysterectomy in women with preoperative
      pain and depression.
AB  - OBJECTIVE: We sought to examine differences in quality of life and sexual
      function after hysterectomy among women with preoperative pain and depression.
      METHODS: We analyzed data from a cohort study of 1,249 women who had
      hysterectomies for benign conditions. Participants were interviewed, before
      surgery and at 5 intervals after, regarding pelvic pain, depression, quality of
      life, and sexual function. We compared quality of life and sexual function at 6
      and 24 months among women with preoperative pelvic pain alone, depression alone,
      both pelvic pain and depression, or neither. RESULTS: At 24 months, women with
      pain and depression had reduced prevalence of pelvic pain (96.7% decreased to
      19.4%), limited physical function (66.1% to 34.3%), impaired mental health (93.3%
      to 38.1%), and limited social function (41.1% to 15.1%). Women with pain only
      improved in pelvic pain (95.1% to 9.3%) and limited activity level (74.3% to
      24.2%). The group with depression only had improvement in impaired mental health
      (85.1% to 33.1%). Dyspareunia decreased in all groups. Compared with women who
      had neither pain nor depression, women with depression and pain had 3 to 5 times
      the odds of continued impaired quality of life: odds ratio (OR) 2.73, 95%
      confidence interval (CI) 1.78-4.19 for limited physical function; OR 3.41, 95% CI
      2.13-5.46 for impaired mental health; OR 5.76, 95% CI 2.79-11.87 for limited
      social function; OR 4.91, 95% CI 2.63-9.16 for continued pelvic pain; and OR
      2.41, 95% CI 1.26-4.62 for dyspareunia. CONCLUSION: Women with pelvic pain and
      depression fare less well 24 months after hysterectomy than women who have either
      disorder alone or neither. Nevertheless, these women improve substantially over
      their preoperative baseline in all the quality of life and sexual function areas
      assessed. LEVEL OF EVIDENCE: II-2

PMID- 15458890
TI  - Hysterectomy in obese women: a comparison of abdominal and vaginal routes.
AB  - OBJECTIVE: To compare perioperative outcome measures of abdominal and vaginal
      hysterectomies in obese women. METHODS: We reviewed the charts of all obese women
      (body mass index more than 30 kg/m(2)) who underwent abdominal or vaginal
      hysterectomy for benign gynecologic conditions in our institution between 1997
      and 2002. Laparoscopically assisted vaginal hysterectomies and hysterectomies
      with concomitant major pelvic or abdominal surgery were excluded. The rate of
      operative and postoperative complications, length of hospitalization, operative
      time, and perioperative change of hemoglobin concentration were analyzed for
      abdominal hysterectomy and vaginal hysterectomy. RESULTS: The study group
      consisted of 369 obese women, of whom 189 (51.2%) underwent abdominal, and 180
      (48.8%), vaginal hysterectomy. Patient characteristics were statistically
      comparable between the groups except for uterine weight, which was higher in the
      abdominal group, and parity, which was greater for women who underwent vaginal
      hysterectomy (P <.05). After controlling for all the significantly different
      variables, vaginal hysterectomy resulted in lower incidence of postoperative
      fever (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.12-0.39), ileus (OR
      0.21, 95% CI 0.06-0.75), urinary tract infection (OR 0.21, 95% CI 0.06-0.75),
      shorter operative time (126.8 +/- 58.7 minutes compared with 109.7 +/- 68.5
      minutes) and length of hospital stay (3.5 +/- 1.9 days compared with 1.9 +/- 1.1
      days). Seven women (3.7%) who underwent abdominal hysterectomy developed wound
      infections during their hospital stay compared with none in the vaginal
      hysterectomy group. CONCLUSION: For obese women, vaginal hysterectomy is superior
      due to its lower incidence of postoperative fever, ileus, and urinary tract
      infection and shorter operative time and hospital stay. LEVEL OF EVIDENCE: II-2

PMID- 15458891
TI  - Increased success of trial of labor after previous vaginal birth after cesarean.
AB  - OBJECTIVE: To estimate whether a history of a previous successful vaginal birth
      after cesarean delivery (VBAC) has an effect on a subsequent VBAC attempt.
      METHODS: A chart review of cases identified from the International Classification
      of Diseases, 9th Revision (ICD-9) codes and cases identified in the logbooks on
      Labor and Delivery yielded 1,216 cases of attempted VBAC from 1996 to 2000. Data
      gathered from these cases included history of previous successful VBAC. Variables
      of interest included previous successful normal spontaneous vaginal delivery,
      history of diabetes, labor induction, and recurrent indication for cesarean
      delivery. RESULTS: Of the 336 patients with a history of one or more previous
      successful VBAC attempts, 94.6% had a subsequent successful VBAC, whereas 70.5%
      of the remaining 880 patients were successful (P <.001). For those patients with
      one or more previous successful normal spontaneous vaginal deliveries, 87.8% had
      a successful VBAC, whereas 75.6% were successful without this history (P =.001).
      The presence of diabetes and a recurrent indication for cesarean delivery both
      decreased VBAC success and were independently associated with poor outcome (P
      <.001). Patients with a history of previous VBAC were 7 times more likely to have
      a subsequent VBAC success (odds ratio 7.40, 95% confidence interval 4.51-12.16; P
      <.001). Those with a history of previous normal spontaneous vaginal delivery were
      not more likely to have a successful VBAC when the other variables were
      controlled. Induction did not affect VBAC outcome. CONCLUSION: A history of a
      previous successful VBAC increases the likelihood for success with future
      attempts. Maternal diabetes and history of a recurrent indication for cesarean
      delivery are poor prognosticators for successful trial of labor. LEVEL OF
      EVIDENCE: II-2

PMID- 15458892
TI  - Reasons for increasing trends in large for gestational age births.
AB  - OBJECTIVE: To describe the magnitude of change in the proportion of term and
      postterm (37 completed weeks or more) large for gestational age (LGA) infants
      between 1992-2001 in Sweden and to examine whether time trends in prevalence of
      LGA births can be explained by changes in maternal risk factors. METHODS: Using
      the population-based Swedish Birth Register, we analyzed data from 1992 through
      2001 on births of women who delivered live, singleton, term infants without
      malformations (N = 874,163). Unconditional logistic regression was used to model
      the odds of LGA birth. RESULTS: Mean birth weight and proportions of LGA births
      and births 4,500 g or more rose during the period 1992 to 2001. An unadjusted
      analysis estimated that the risk of LGA birth increased by 23% over 10 years.
      However, the prevalence of overweight and obesity (body mass index of 25 or
      greater) increased from 25% to 36%, and the prevalence of smoking decreased from
      23% to 11% during the same period. After adjusting trends in all covariates
      simultaneously, the association between risk of LGA birth and calendar year
      disappeared. CONCLUSION: The increasing proportions of LGA births over time is
      explained by concurrent increases in maternal body mass index and decreases in
      maternal smoking. With the increasing prevalence of overweight among adolescents
      and young women, the prevalence of LGA infants and associated risks may increase
      over time. LEVEL OF EVIDENCE: II-2

PMID- 15458893
TI  - Advanced maternal age and adverse perinatal outcome.
AB  - OBJECTIVE: The aim of this study was to investigate the influence of maternal age
      on perinatal and obstetric outcome in women aged 40-44 years and those 45 years
      or older and to estimate whether adverse outcome was related to intercurrent
      illness and pregnancy complications. METHODS: National prospective, population
      based, cohort study in women aged 40-44 years and those 45 years or older and in
      a control group of women aged 20-29 years who delivered during the period 1987
      2001. Adjusted odds ratios (OR) were calculated after adjustments for significant
      malformations, maternal pre-existing diseases, and smoking. Main outcome measures
      were perinatal mortality, intrauterine fetal death, neonatal death, preterm
      birth, and preeclampsia. RESULTS: During the 15-year period, there were 1,566,313
      deliveries (876,361 women were 20-29 years of age, 31,662 were 40-44 years, and
      1,205 were > or = 45 years). Perinatal mortality was 1.4%, 1.0%, and 0.5% in
      women 45 years or older, 40-44, and 20-29 years, respectively. Adjusted OR for
      perinatal mortality was 2.4 (95% confidence interval [CI] 1.5-4.0) in women aged
      45 years or older, compared with 1.7 (95% CI 1.5-1.9) in women 40-44 years.
      Adjusted OR for intrauterine fetal death was 3.8 (95% CI 2.2-6.4) in women aged
      45 years or older, compared with 2.1 (95% CI 1.8-2.4) in women 40-44 years.
      Preterm birth, gestational diabetes, and preeclampsia were more common among
      women 40-44 years of age and those 45 years or older. Perinatal mortality was
      increased in women with intercurrent illness or pregnancy complications compared
      with women without these conditions, but there was no evidence that these factors
      became more important with increasing age. CONCLUSION: Perinatal mortality,
      intrauterine fetal death, and neonatal death increased with age. There was also
      an increase in intercurrent illnesses and pregnancy complications with increasing
      age, but this did not entirely explain the observed increase in perinatal
      mortality with age. LEVEL OF EVIDENCE: II-3

PMID- 15458894
TI  - Racial disparity in stillbirth among singleton, twin, and triplet gestations in
      the United States.
AB  - OBJECTIVE: We investigated the relationship between maternal race and stillbirth
      among singletons, twins, and triplets. METHODS: We conducted a retrospective
      cohort study on 14,348,318 singletons, 387,419 twins, and 20,953 triplets
      delivered in the United States from 1995 through 1998. We compared the risk of
      stillbirth between pregnancies of black and those of white mothers using the
      generalized estimating equations framework to adjust for intracluster correlation
      in multiples. RESULTS: The proportion of black infants was 16%, 18%, and 8% among
      singletons, twins, and triplets, respectively. Crude stillbirth rate among
      singletons was 6.6 per 1,000 and 3.5 per 1,000 for black and white fetuses,
      respectively. Among twins, 796 stillbirths (11.6 per 1,000) were recorded for
      black mothers versus 3,209 stillbirths (10.1 per 1,000) among white mothers,
      whereas among triplets there were 233 stillbirths, of which 39 stillbirths were
      black fetuses (24.6 per 1,000) and 194 stillbirths were white fetuses (10.0 per
      1,000). Black singletons, twins, and triplets weighed 278 g, 186 g, and 216 g
      less than white fetuses, respectively (P <.001). Risk of stillbirth was elevated
      in black fetuses compared with white fetuses among singletons (adjusted odds
      ratio [OR] 2.9, 95% confidence interval [CI] 2.8-3.0) and twins (OR 1.3. 95% CI
      1.2-1.4) but comparable among triplets (OR 1.2, 95% CI 0.7-2.1). This decreasing
      trend was significant (P for trend <.001). CONCLUSION: The disparity of
      stillbirths between black and white fetuses still persists among singletons and
      twins. Among triplet gestations, however, the 2 racial groups have a comparable
      risk level. Our findings highlight the need for a rigorous research agenda to
      elucidate causes of stillbirth across racial/ethnic entities in the United
      States. LEVEL OF EVIDENCE: II-2

PMID- 15458895
TI  - Population density and teen pregnancy.
AB  - OBJECTIVE: The relationship between population density and the percentage of
      teens who electively terminate their pregnancy was the focus of this study.
      METHODS: The United States population density was determined for each state and
      each district of the American College of Obstetricians and Gynecologists (ACOG)
      from the 2000 US Census. The United States teenage pregnancy statistics for
      females aged 15 to 19 years in 1999 and 2000 were obtained from the Alan
      Guttmacher Institute. The main measures were the correlation between population
      density and teen pregnancy rate or teen abortion rate by state and ACOG district.
      RESULTS: In 2000 there was no significant correlation between population density
      and the percentage of teenage females who conceived when analyzed by ACOG
      district (correlation coefficient r = 0.063, P =.87). In contrast, there was a
      significant correlation between population density and the percentage of pregnant
      teens who electively terminated their pregnancy when analyzed by ACOG district (r
      = 0.85, P =.003). In regions of greatest population density the percentage of
      pregnant teens who electively terminated was about 50%. In regions of least
      population density the percentage of pregnant teens who electively terminated was
      about 25%. Similar results were observed when teen pregnancy and abortion data
      from 1999 were analyzed. CONCLUSION: In the United States population density is
      not associated with the percentage of teenage females who become pregnant, but it
      is positively correlated with the percentage of pregnant teens that electively
      terminate their pregnancy. In areas of low population density teens who become
      pregnant may prefer birth to pregnancy termination. Alternatively, the access to
      pregnancy termination services may be suboptimal for teens in geographic areas
      with low population density. LEVEL OF EVIDENCE: II-2

PMID- 15458896
TI  - A randomized trial of the Fischer cone biopsy excisor and loop electrosurgical
      excision procedure.
AB  - OBJECTIVE: To compare specimens obtained with the Fischer cone biopsy excisor or
      loop electrosurgical excision procedure (LEEP) with respect to number of
      specimens obtained, margin interpretability, adequacy of excision, and ease of
      use. METHODS: One hundred eligible patients aged 13 years and older were randomly
      assigned to treatment with the Fischer cone biopsy excisor or LEEP. Eligibility
      criteria included: (1) cervical intraepithelial neoplasia (CIN) 2 or 3, (2)
      persistent CIN 1, or (3) cytologic/histologic discrepancy. Following excision,
      providers ranked ease of use on a scale of 1 to 10. A pathologist blinded to
      procedure type analyzed specimens for margin interpretability and adequacy of
      excision. Before study initiation we calculated that a total of 100 patients
      would be required to demonstrate a significant difference in the interpretable
      margin rate of 80% for LEEP and 99% for cone biopsy excisor (power 80%, alpha
      =.05). RESULTS: After adjustment for ease of use, lesion size, and degree of
      neoplasia, the cone biopsy excisor was no more likely to result in a single
      specimen than LEEP (74% versus 63%, relative risk [RR] 0.93, 95% confidence
      interval [CI] 0.79 -1.11), to result in a specimen with interpretable margins
      (65% versus 73%, RR 0.97, 95% CI 0.78-1.22), or to result in a fully excised
      cervical lesion (72% versus 62% for LEEPs, RR 1.08, 95% CI 0.77-1.52). Providers
      found their experiences with both Fischer cone biopsy excisor and LEEP cone
      biopsies to be similar, even after adjustment for year of training and previous
      experience (RR 0.95, 95% CI 0.72-1.24). CONCLUSION: The Fischer cone biopsy
      excisor and LEEP performed similarly with respect to the number of final
      specimens, margin interpretability, and ease of use. LEVEL OF EVIDENCE: I

PMID- 15458897
TI  - Regression of low-grade cervical intraepithelial neoplasia in patients with HLA
      DRB1*13 genotype.
AB  - OBJECTIVE: The human leukocyte antigen (HLA)-DRB1*13 allele frequency is lower in
      women with cervical carcinoma than in the general population, suggesting that
      this allele could exert a protective effect against progression of cervical
      intraepithelial neoplasia (CIN) associated with human papillomaviruses (HPV). To
      test this hypothesis, we designed a prospective study of low-grade CIN (CIN1) and
      analyzed the probability of regression of these lesions according to HLA-DR and
      HPV status. METHODS: The study sample was composed of 86 women with CIN1 who
      agreed to regular colposcopic follow-up and no immediate treatment. Biopsy
      specimens were taken under colposcopy for histology and for the determination of
      HPV and HLA status. Cases were classified into 3 groups: CIN1 regression,
      persistence for at least 12 months, or progression to CIN2 or 3. RESULTS: The
      rate of spontaneous regression (95% confidence interval) at 24 months was 51.6%
      (39-61.6%) overall compared with 34.7% (13.4-50.8%) in HPV16/18 positive cases
      and 59.9% (43.7-71.4%) in HPV16/18-negative cases (P =.051). The rate of
      regression was 71.8% (40.8-86.5%) in patients with HLA-DRB1*13 and 45.9% (31.5
      57.2%) in patients with other genotypes (P =.03). Regression reached 90.5% (38.9
      98.5%) at 18 months in DRB1*13 patients with HPV16/18-negative-associated CIN
      (15.1% of the cases). In multivariable analysis, HLA-DRB1*13 allele and HPV16/18
      negative status were independently associated with an increased probability for
      regression (adjusted hazard ratio 2.1 [1.0-4.1] and 2.5 [1.2-5.4], respectively).
      CONCLUSION: A subset of approximately 15% of CIN1 highly likely to show
      spontaneous regression can be defined using 2 biologic parameters that
      characterize the viral causative agent and the host. LEVEL OF EVIDENCE: II-2

PMID- 15458898
TI  - Frequency of douching and risk of bacterial vaginosis in African-American women.
AB  - OBJECTIVE: Frequent vaginal douching has been associated with bacterial
      vaginosis. We investigated whether infrequent douching is also a risk factor for
      bacterial vaginosis. METHODS: In this cross-sectional study, we recruited 411
      African-American women of reproductive age who were visiting gynecologic or
      family planning clinics of 2 hospitals in New York City from 1999 to 2001.
      Detailed information on demographic characteristics, feminine hygiene practice,
      contraceptive use, and reproductive and medical history was collected through in
      person interview. Pelvic examinations and laboratory tests on vaginal secretions
      were performed. Bacterial vaginosis was defined as Gram stain score of 7 or
      greater. RESULTS: The overall prevalence of bacterial vaginosis in this
      population was 27%, similar to the national average. Water-vinegar solution was
      the most common douche. Although one half of the subjects reported douching
      regularly, only 2% douched frequently (once per week or more). Frequent douching
      in the past 3 months had a prevalence ratio of bacterial vaginosis of 2.35 (95%
      confidence interval 0.98-5.63). However, douching less than once per week was not
      associated with bacterial vaginosis. CONCLUSION: Douching less than once per
      week, particularly with a water-vinegar douche, is not associated with bacterial
      vaginosis in this African-American population. LEVEL OF EVIDENCE: III

PMID- 15458899
TI  - Bacterial vaginosis and risk of pelvic inflammatory disease.
AB  - BACKGROUND: Bacterial vaginosis commonly is found in women with pelvic
      inflammatory disease (PID), but it is unclear whether bacterial vaginosis leads
      to incident PID. METHODS: Women (n = 1,179) from 5 U.S. centers were evaluated
      for a median of 3 years. Every 6-12 months, vaginal swabs were obtained for gram
      stain and culture of microflora. A vaginal microflora gram stain score of 7-10
      was categorized as bacterial vaginosis. Pelvic inflammatory disease was diagnosed
      by presence of either histologic endometritis or pelvic pain and tenderness plus
      one of the following: oral temperature greater than 38.3 degrees C; sedimentation
      rate greater than 15 mm/hour; white blood count greater than 10,000; or lower
      genital tract detection of leukorrhea, mucopus, or Neisseria gonorrhoeae or
      Chlamydia trachomatis. RESULTS: After adjustment for relevant demographic and
      lifestyle factors, baseline bacterial vaginosis was not associated with the
      development of PID (adjusted hazard ratio 0.89, 95% confidence interval 0.55
      1.45). Carriage of bacterial vaginosis in the previous 6 months before a
      diagnosis (adjusted risk ratio 1.31, 95% confidence interval 0.71-2.42) also was
      not significantly associated with PID. Similarly, neither absence of hydrogen
      peroxide-producing Lactobacillus nor high levels of Gardnerella vaginalis
      significantly increased the risk of PID. Dense growth of pigmented, anaerobic
      gram-negative rods in the 6 months before diagnosis did significantly increase a
      woman's risk of PID (P =.04). One subgroup of women, women with 2 or more recent
      sexual partners, demonstrated associations among bacterial vaginosis, Gardnerella
      vaginalis, anaerobic gram-negative rods, and PID. CONCLUSION: In this cohort of
      high-risk women, after adjustment for confounding factors, we found no overall
      increased risk of developing incident PID among women with bacterial vaginosis.
      LEVEL OF EVIDENCE: II-2

PMID- 15458900
TI  - A brief screening instrument to detect posttraumatic stress disorder in
      outpatient gynecology.
AB  - OBJECTIVE: Posttraumatic stress disorder (PTSD) is a serious anxiety disorder
      triggered by the experience of trauma. One in 4 individuals exposed to trauma
      will develop PTSD. Victims of trauma are frequent users of health care, but
      screening is rarely done and most sequelae remain undetected. Our objectives were
      1) to document the prevalence of a trauma history among women seeking routine
      gynecologic care and 2) to evaluate a 4-item screening instrument for PTSD for
      triaging women with a trauma history for further evaluation. METHODS: We
      conducted a cross-sectional survey of women presenting to the University of North
      Carolina outpatient gynecology clinic for an annual examination. Written surveys
      included medical history and health status, trauma history (including type), and
      PTSD symptoms using the screening instrument. Patients with trauma who agreed to
      further participation received a structured clinical interview to diagnose PTSD.
      RESULTS: Seventy-six percent of patients (N = 292) completed the survey, and 88
      (30%) reported a history of 1 or more traumatic event or events. Thirty-two of
      the 88 completed the psychiatric assessment, and 25 of 32 (78%) met Diagnostic
      and Statistical Manual of Mental Disorders, 4th edition criteria for PTSD. Mean
      age was 34 years, 49% were African American, and 46% were unmarried. Compared
      with the structured clinical interview, the screening instrument performed with a
      sensitivity of 72% (95% confidence interval [CI] 0.51-0.88) and a specificity of
      71% (95% CI 0.29-0.96), corresponding to a positive likelihood ratio of 2.52 (95%
      CI 0.76-8.34) and a negative likelihood ratio of 0.39 (95% CI 0.18-0.86).
      CONCLUSION: Trauma was common in this population. Including a screening
      instrument for trauma and PTSD on clinic intake surveys has promise for use as a
      triage tool. Use of such an instrument could meaningfully increase detection of
      PTSD among women receiving routine preventive care. LEVEL OF EVIDENCE: III

PMID- 15458901
TI  - Periodontal disease and upper genital tract inflammation in early spontaneous
      preterm birth.
AB  - OBJECTIVE: To estimate the relationship between maternal periodontal disease and
      both early spontaneous preterm birth and selected markers of upper genital tract
      inflammation. METHODS: In this case-control study, periodontal assessment was
      performed in 59 women who experienced an early spontaneous preterm birth at less
      than 32 weeks of gestation, in a control population of 36 women who experienced
      an early indicated preterm birth at less than 32 weeks of gestation, and in 44
      women with an uncomplicated birth at term (>or = 37 weeks). Periodontal disease
      was defined by the degree of attachment loss. Cultures of the placenta and
      umbilical cord blood, cord interleukin-6 levels, and histopathologic examination
      of the placenta were performed for all women. RESULTS: Severe periodontal disease
      was more common in the spontaneous preterm birth group (49%) than in the
      indicated preterm (25%, P =.02) and term control groups (30%, P =.045).
      Multivariable analyses, controlling for possible confounders, supported the
      association between severe periodontal disease and spontaneous preterm birth
      (odds ratio 3.4, 95% confidence interval 1.5-7.7). Neither histologic
      chorioamnionitis, a positive placental culture, nor an elevated cord plasma
      interleukin-6 level was significantly associated with periodontal disease (80%
      power to detect a 50% difference in rate of histological chorioamnionitis, alpha
      = 0.05). CONCLUSION: Women with early spontaneous preterm birth were more likely
      to have severe periodontal disease than women with indicated preterm birth or
      term birth. Periodontal disease was not associated with selected markers of upper
      genital tract inflammation. LEVEL OF EVIDENCE: II-2

PMID- 15458902
TI  - Recurrent fetal aneuploidy and recurrent miscarriage.
AB  - OBJECTIVE: Some investigators have found a high frequency of abortus aneuploidy
      in women with recurrent miscarriage, suggesting the possibility of recurrent
      aneuploidy as a cause of recurrent miscarriage. Others contend that aneuploidy is
      not a cause of recurrent miscarriage. The purpose of this study was to
      investigate the relationship between fetal aneuploidy and recurrent miscarriage
      by estimating whether fetal aneuploidy is more common in patients with recurrent
      miscarriage than in patients with sporadic miscarriage METHODS: Recurrent
      miscarriage cases (n = 135) included women who had a subsequent miscarriage in
      which an abortus karyotype was obtained. Controls (n = 150) were patients
      experiencing a sporadic miscarriage who had fetal karyotypes performed as part of
      a study to assess the utility of abortus tissue for transplantation. Karyotype
      analysis was performed using standard G-banding techniques. RESULTS: Abortuses
      from 122 cases and 133 controls were successfully karyotyped. Thirty-one (25.4%)
      abortuses from cases and 56 (42.1%) from controls were aneuploid (odds ratio
      0.47, 95% confidence interval 0.27-0.80). Aneuploid abortuses occurred in 20% of
      cases and 25% of controls, aged 20-29 years, 19% of cases and 24% of controls,
      aged 30-34 years, 35% of cases and 47% of controls, aged 35-39 years, and 50% of
      both cases and controls, aged 40 years or older (not significant). Of 30 cases in
      whom 2 or more miscarriages were karyotyped, 3 (10%) had aneuploidy in each
      abortus. CONCLUSION: In our population of recurrent miscarriage patients, abortus
      aneuploidy occurred significantly less often than in sporadic miscarriages. The
      rate of aneuploidy in this study was considerably lower than reported in other
      studies. If recurrent aneuploidy contributes to recurrent miscarriage, it does so
      in only a small number of patients. LEVEL OF EVIDENCE: II-2

PMID- 15458903
TI  - Time and the risk of ruptured tubal pregnancy.
AB  - OBJECTIVE: Tubal pregnancy remains an important cause of maternal morbidity and
      mortality. We sought to quantify the relationship of time between symptom onset
      and treatment and the risk of tubal rupture. METHODS: We reviewed inpatient,
      clinic, and physician office charts of 221 women with tubal pregnancy. We
      assessed the conditional risk of rupture with passing time and other factors
      related to rupture. RESULTS: Time between symptom onset and treatment varied from
      3 hours to 66 days with an average of 7 days. There was a 32% rupture rate. The
      conditional risk of rupture was highest within the first 48 hours of symptom
      onset (5-7%). The risk dropped, leveled off, and remained fairly steady at
      approximately 2.5% per 24 hours of untreated symptoms. Classic tubal pregnancy
      signs, symptoms, and tests were not helpful in predicting rupture. CONCLUSION:
      The rate of rupture is highest in women with the shortest times between symptom
      onset and treatment. With passing time, the risk declines, but remains steady
      despite women's getting into care. LEVEL OF EVIDENCE: II-2

PMID- 15458904
TI  - Pessary test to predict postoperative urinary incontinence in women undergoing
      hysterectomy for prolapse.
AB  - OBJECTIVE: We sought to demonstrate that a positive pessary test could predict
      postsurgical stress urinary incontinence in women with severe pelvic organ
      prolapse and that performing tension-free vaginal taping (TVT) could effectively
      prevent its occurrence. METHODS: Among the 79 patients evaluated for severe
      pelvic organ prolapse without symptoms of stress urinary incontinence, all
      underwent meticulous urogynecologic evaluations and pessary testing. In group 1,
      32 patients had positive pessary tests and underwent vaginal hysterectomy,
      anterior and posterior colporrhaphy, and TVT. In group 2, 47 patients (17 of whom
      had positive pessary tests and 30 of whom had negative pessary tests) underwent
      vaginal hysterectomy and anterior and posterior colporrhaphy alone. A comparison
      in terms of surgical outcome and clinical manifestations was made between these 2
      groups of patients. RESULTS: After surgery, a small proportion of patients had de
      novo idiopathic detrusor overactivity (7.6%, n = 6), urinary tract infections
      (7.6%, n = 6), mild recurrent prolapse (5.1%, n = 4), and urinary retention
      (3.8%, n = 3). Eleven (64.7%) of 17 patients with positive pessary tests who did
      not undergo TVT had urine leakage after their hysterectomies in contrast with the
      30 patients who had negative pessary test, none of whom developed symptomatic
      stress urinary incontinence after vaginal hysterectomy. Among the 32 patients
      with positive pessary tests who had TVT with their hysterectomies, 3 developed
      urine leakage later; the cure rate was 90.6%. CONCLUSION: Continent patients
      suffering from severe pelvic organ prolapse but with a positive pessary test are
      considered to be at high risk of developing postoperative symptomatic stress
      urinary incontinence. Among the patients in our medium-range study, TVT
      effectively prevented postsurgical urinary incontinence. LEVEL OF EVIDENCE: II-1

PMID- 15458905
TI  - Antral follicle count and serum follicle-stimulating hormone levels to assess
      functional ovarian age.
AB  - OBJECTIVE: The objective of this study was 2-fold. The first was to estimate side
      to-side variation in antral follicle counts. The second was to determine whether
      basal follicle-stimulating hormone levels on days 2, 3, and 4 of the same
      menstrual cycle are significantly different. METHODS: Forty-one patients between
      the ages of 20 and 42 years undergoing monitoring for in vitro fertilization
      embryo transfer were evaluated ultrasonographically for antral follicle number.
      The antral follicle counts were determined for each ovary by experienced
      ultrasonographers at the time of suppression check ultrasonography. In a separate
      study, 62 normal subjects (ages 20-25 and 40-45 years) underwent serial
      sequential serum follicle-stimulating hormone determinations on days 2-4 of the
      menstrual cycle, and these levels were compared. RESULTS: There was no
      significant difference between right and left antral follicle counts (P =.30).
      Serial follicle-stimulating hormone values were not significantly different on
      days 2, 3, or 4 of the menstrual cycle (P =.22). CONCLUSION: There is no
      significant difference between right-sided and left-sided antral follicle counts
      within the same individual. In turn, there is no significant difference in serial
      follicle-stimulating hormone levels on days 2, 3, or 4 of the menstrual cycle.
      LEVEL OF EVIDENCE: III

PMID- 15458906
TI  - Abdominal sacrocolpopexy: a comprehensive review.
AB  - OBJECTIVE: To summarize published data about abdominal sacrocolpopexy and to
      highlight areas about which data are lacking. DATA SOURCES: We conducted a
      literature search on MEDLINE using Ovid and PubMed, from January,1966 to January,
      2004, using search terms "sacropexy," "sacrocolpopexy," "sacral colpopexy,"
      "colpopexy," "sacropexy," "colposacropexy," "abdominal sacrocolpopexy" "pelvic
      organ prolapse and surgery," and "vaginal vault prolapse or surgery" and included
      articles with English-language abstracts. We examined reference lists of
      published articles to identify other articles not found on the electronic search.
      METHODS OF STUDY SELECTION: We examined all studies identified in our search that
      provided any outcome data on sacrocolpopexy. Because of the substantial
      heterogeneity of outcome measures and follow-up intervals in case studies, we did
      not apply meta-analytic techniques to the data. TABULATION, INTEGRATION, AND
      RESULTS: Follow-up duration for most studies ranged from 6 months to 3 years. The
      success rate, when defined as lack of apical prolapse postoperatively, ranged
      from 78-100% and when defined as no postoperative prolapse, from 58-100%. The
      median reoperation rates for pelvic organ prolapse and for stress urinary
      incontinence in the studies that reported these outcomes were 4.4% (range 0
      18.2%) and 4.9% (range 1.2% to 30.9%), respectively. The overall rate of mesh
      erosion was 3.4% (70 of 2,178). Some reports found more mesh erosions when
      concomitant total hysterectomy was done, whereas other reports did not. There
      were no data to either support or refute the contentions that concomitant
      culdoplasty or paravaginal repair decreased the risk of failure. Most authors
      recommended burying the graft under the peritoneum to attempt to decrease the
      risk of bowel obstruction; despite this, the median rate (when reported) of small
      bowel obstruction requiring surgery was 1.1% (range 0.6% to 8.6%). Few studies
      rigorously assessed pelvic symptoms, bowel function, or sexual function.
      CONCLUSION: Sacrocolpopexy is a reliable procedure that effectively and
      consistently resolves vaginal vault prolapse. Patients should be counseled about
      the low, but present risk, of reoperation for prolapse, stress incontinence, and
      complications. Prospective trials are needed to understand the effect of
      sacrocolpopexy on functional outcomes.

PMID- 15458907
TI  - Phytoestrogens for treatment of menopausal symptoms: a systematic review.
AB  - OBJECTIVE: To assess the efficacy and tolerability of phytoestrogens for
      treatment of menopausal symptoms. DATA SOURCES: We searched the Cochrane Library
      and MEDLINE from 1966 to March 2004, using a detailed list of terms related to
      phytoestrogens and menopausal symptoms and also hand-searched abstracts from
      relevant meetings. METHODS OF STUDY SELECTION: Randomized trials were eligible if
      they involved symptomatic perimenopausal or postmenopausal women, compared
      phytoestrogen with placebo or control, reported hot flush frequency or menopausal
      symptom scores, and were at least 4 weeks in duration. TABULATION, INTEGRATION,
      AND RESULTS: Data were extracted onto standardized forms using a prospectively
      developed protocol. Twenty-five trials involving 2,348 participants met criteria.
      At baseline, the mean age was 53.1 years, mean duration of menopause was 4.3
      years, and mean daily hot flush frequency was 7.1. Mean study duration was 17
      weeks. Trials were grouped into categories according to type of phytoestrogen:
      soy foods, beverages, or powders (n = 11); soy extracts (n = 9); and red clover
      extracts (n = 5). Of the 8 soy food trials reporting hot flush frequency
      outcomes, 7 were negative. Five trials of soy foods provided information to
      calculate effect sizes; these were in the small-to-medium range, favoring placebo
      in 3 trials and soy in 2. Of the 5 soy extract trials reporting hot flush
      frequency, 3 (including the 2 largest trials) were negative. Effect sizes were
      calculated for 2 soy extract trials: one favored placebo with small effect size
      and the other favored soy with moderate effect size. Red clover trials showed no
      improvement in hot flush frequency (weighted mean difference -0.60, 95%
      confidence interval -1.71 to 0.51). Adverse effects were primarily
      gastrointestinal and taste intolerance in the soy food and beverage trials.
      CONCLUSION: The available evidence suggests that phytoestrogens available as soy
      foods, soy extracts, and red clover extracts do not improve hot flushes or other
      menopausal symptoms.

PMID- 15458908
TI  - Safety and adverse effects associated with raloxifene: multiple outcomes of
      raloxifene evaluation.
AB  - OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur
      with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes
      of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled
      7,705 postmenopausal women with osteoporosis. Women were randomly assigned to
      raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous
      thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or
      cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated
      with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95%
      confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman
      years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170
      (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in
      the placebo group for the first 2 years, but decreased to about the same rate as
      in the placebo group thereafter. Raloxifene did not increase risk for cataracts
      (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3),
      endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9;
      95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for
      venous thromboembolism, but there was no increased risk for cataracts,
      gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF
      EVIDENCE: I

PMID- 15458909
TI  - Premenstrual syndrome, premenstrual dysphoric disorder, and beyond: a clinical
      primer for practitioners.
AB  - The management of adverse premenstrual symptoms has presented a difficult
      challenge for clinicians. However, based on numerous well-designed research
      studies over the last decade, we now have diagnostic criteria for the severe form
      of the syndrome, premenstrual dysphoric disorder, and a variety of evidence-based
      therapeutic strategies. This review presents a comprehensive, practical
      description of what the clinician needs to know to diagnose and treat adverse
      premenstrual symptoms at all levels of severity. Diagnostic criteria are
      described in detail, including a discussion of the distinction between
      premenstrual dysphoric disorder and premenstrual syndrome (PMS). The rationale
      for including prospective symptom calendars as a routine part of the diagnostic
      evaluation of severe symptoms is presented. The differential diagnosis of cyclic
      symptoms, including depression and anxiety disorders, menstrual migraine, and
      mastalgia, and an approach for the management of each of these problems are
      presented. A treatment approach is recommended that matches the treatment to the
      degree of problems the woman is experiencing. Serotonin reuptake inhibitors are
      the treatment of choice for severe symptoms, and most women with PMS/premenstrual
      dysphoric disorder will respond to intermittent, luteal phase-only therapy.
      Ovulation suppression should be reserved for women who do not respond to other
      forms of therapy. The role of oophorectomy is limited, and guidelines for its use
      are presented.

PMID- 15458911
TI  - Hysterectomy versus expanded medical treatment for abnormal uterine bleeding:
      clinical outcomes in the medicine or surgery trial.

PMID- 15458912
TI  - Perinatal outcome among singleton infants conceived through assisted reproductive
      technology in the United States.

PMID- 15458915
TI  - ACOG Practice Bulletin #56: Multiple gestation: complicated twin, triplet, and
      high-order multifetal pregnancy.

PMID- 15458916
TI  - ACOG Committee Opinion #300: Cervical cancer screening in adolescents.

PMID- 15458917
TI  - ACOG Committee Opinion #301: Sexually transmitted diseases in adolescents.

PMID- 15458918
TI  - ACOG Committee Opinion #302: Guidelines for Adolescent Health Research.

PMID- 15458919
TI  - ACOG Committee Opinion #303: Inappropriate use of the terms fetal distress and
      birth asphyxia.

PMID- 15458920
TI  - Transcriptional regulation of murine Slc22a1 (Oct1) by peroxisome proliferator
      agonist receptor-alpha and -gamma.
AB  - The transport and metabolism of organic cationic endobiotics, nutrients, and
      drugs are essential hepatic functions. Slc22A1 is the basolateral liver
      transporter mediating the uptake of organic cations; however, little is known
      about the regulation of this transport protein. Peroxisome proliferator agonist
      receptor (PPAR)-alpha and -gamma agonists are commonly used agents that regulate
      many hepatocellular transport functions. Thus the purpose of this study was to
      examine the effects of PPAR agonists on the hepatic regulation and function of
      Slc22a1. Mice and H35 cells were administered PPAR-alpha and -gamma agonists, and
      the effect on Slc22a1 gene expression was measured. We subsequently cloned the
      Slc22a1 promoter and employed chimeric constructs to assay Slc22a1 gene
      transcription. The effects of PPAR-agonist treatment on organic cation uptake was
      also assayed. Slc22a1 expression was increased by PPAR-alpha and -gamma agonist
      treatment in both murine livers and H35 cells. Gene expression in H35 cells was
      further increased following transfection with expression vectors of PPAR
      transcription factors and PPAR agonist treatment. We cloned the promoter region
      of Slc22a1 and identified a PPAR-response element, and transfections with
      chimeric Slc22a1; promoter-reporter gene constructs demonstrate that the
      increased gene expression was transcriptionally regulated. Functional assays
      confirmed that cells treated with PPAR agonists displayed significant increases
      in organic cation uptake. PPAR-alpha and -gamma agonists transcriptionally
      increase Slc22a1 gene expression, and the increased Slc22a1 expression results in
      enhanced cellular organic cation uptake. These studies may have implication for
      the uptake of organic cationic drugs and for lipid metabolism.

PMID- 15458921
TI  - Ecabet sodium inhibits Helicobacter pylori lipopolysaccharide-induced activation
      of NADPH oxidase 1 or apoptosis of guinea pig gastric mucosal cells.
AB  - Helicobacter pylori LPS activates a homolog of gp91(phox), NADPH oxidase 1
      (Nox1), in guinea pig gastric mucosal cells cultured in 10% FBS-containing
      medium. RT-PCR and Northern hybridization demonstrated that H. pylori LPS
      stimulated expression of Nox1 and a novel p47(phox) homolog (Noxo1) mRNAs with a
      peak at 4 h, followed by upregulation of superoxide anion (O2-) generation.
      Pretreatment with 10 mg/ml of a nonabsorbable antigastric ulcer drug, ecabet
      sodium (ecabet), completely blocked these two mRNA expressions and the
      upregulation of O2- production. Under low (0.1%)-FBS conditions, H. pylori LPS
      predominantly caused apoptosis of the cells. Ecabet completely blocked the LPS
      triggered phosphorylation of transforming growth factor-beta-activated kinase 1
      (TAK1) and TAK1-binding protein 1, activation of caspase 8, loss of mitochondrial
      membrane potential, release of cytochrome c, activation of caspase 3, and
      appearance of apoptotic cells. In contrast, ecabet had no effect on ethanol- or
      etoposide-initiated apoptosis. The ecabet-pretreated cells exhibited the
      responsiveness to H. pylori LPS, similarly as untreated control cells did, when
      ecabet was removed by washing before the addition of H. pylori LPS. Incubation of
      H. pylori LPS with ecabet eliminated the toxic effects of the LPS, and
      nondenatured polyacrylamide gel electrophoresis indicated the formation of higher
      molecular mass complexes between H. pylori LPS and ecabet, suggesting that ecabet
      may interact with H. pylori LPS and block the activation of Toll-like receptor 4
      (TLR4). Our results suggest that ecabet may suppress TLR4-mediated inflammation
      or accelerated apoptosis caused H. pylori infection.

PMID- 15458922
TI  - IQGAPs are differentially expressed and regulated in polarized gastric epithelial
      cells.
AB  - IQGAPs, GTPase-activating proteins with an IQ motif, are thought to regulate many
      actin cytoskeleton-based activities through interactions with Cdc42 and Rac.
      Recently, Cdc42 was implicated in regulation of gastric parietal cell HCl
      secretion, and IQGAP2 was immunolocalized with Cdc42 to F-actin-rich
      intracellular canalicular membranes of isolated gastric parietal cells in primary
      culture. Here we sought to define distribution and localization of IQGAP1 and
      IQGAP2 in major oxyntic (acid-secreting) gastric mucosal cell types and to
      determine whether secretory agonists modulate these proteins. Differential
      staining protocols were used to identify different cell populations (parietal,
      chief, surface/pit, and mucous neck cells) in semi-intact glands isolated from
      rabbit gastric mucosae and to characterize these same cells after dispersion and
      fractionation on isopycnic density gradients with simultaneous staining for F
      actin, H+-K+-ATPase, and GSII lectin-binding sites. There was a pronounced
      increase in intracellular F-actin staining in dispersed chief cells, apparently
      from internalization of F-actin-rich apical membranes that normally abut the
      gland lumen. Therefore, other membrane-associated proteins might also be
      redistributed by disruption of cell-cell contacts. Western blot analyses were
      used to quantitate relative concentrations of IQGAPs in defined mucosal cell
      fractions, and gastric glands were used for in situ localizations. We detected
      uniform levels of IQGAP2 expression in oxyntic mucosal cells with predominant
      targeting to regions of cell-cell contact and nuclei of all cell types. IQGAP2
      was not detected in parietal cell intracellular canaliculi. IQGAP1 expression was
      variable and targeted predominantly to the cortex of chief and mucous neck cells.
      Parietal cells expressed little or no IQGAP1 vs. other mucosal cell types.
      Phosphoprotein affinity chromatography, isoelectric focusing, and phosphorylation
      site analyses indicated that both IQGAP1 and IQGAP2 are phosphoproteins
      potentially regulated by [Ca2+]i/PKC and cAMP signaling pathways, respectively.
      Stimulation of glands with carbachol, which elevates [Ca2+]i and activates PKC,
      induced apparent translocation of IQGAP1, but not IQGAP2, to apical poles of
      chief (zymogen) and mucous neck cells. This response was mimicked by PMA but not
      by ionomycin or by elevation of [cAMP]i with forskolin. Our observations support
      a novel, PKC-dependent role for IQGAP1 in regulated exocytosis and suggest that
      IQGAP2 may play a more general role in regulating cell-cell interactions and
      possibly migration within the gastric mucosa.

PMID- 15458923
TI  - Induced microsomal PGE synthase-1 is involved in cyclooxygenase-2-dependent PGE2
      production in gastric fibroblasts.
AB  - We have previously shown that the cyclooxygenase (COX)-2/PGE2 pathway plays a key
      role in VEGF production in gastric fibroblasts. Recent studies have identified
      three PGE synthase (PGES) isozymes: cytosolic PGES (cPGES) and microsomal PGES
      (mPGES)-1 and -2, but little is known regarding the expression and roles of these
      enzymes in gastric fibroblasts. Thus we examined IL-1beta-stimulated mPGES-1 and
      cPGES mRNA and protein expression in gastric fibroblasts by quantitative PCR and
      Western blot analysis, respectively, and studied both their relationship to COX-1
      and -2 and their roles in PGE2 and VEGF production in vitro. IL-1beta stimulated
      increases in both COX-2 and mPGES-1 mRNA and protein expression levels. However,
      COX-2 mRNA and protein expression were more rapidly induced than mPGES-1 mRNA and
      protein expression. Furthermore, MK-886, a nonselective mPGES-1 inhibitor, failed
      to inhibit IL-1beta-induced PGE2 release at the 8-h time point, while totally
      inhibiting PGE2 at the later stage. However, MK-886 did inhibit IL-1beta
      stimulated PGES activity in vitro by 86.8%. N-(2-cyclohexyloxy-4-nitrophenyl)
      methanesulfonamide (NS-398), a selective COX-2 inhibitor, totally inhibited PGE2
      production at both the 8-h and 24-h time points, suggesting that COX-2-dependent
      PGE2 generation does not depend on mPGES-1 activity at the early stage. In
      contrast, NS-398 did not inhibit VEGF production at 8 h, and only partially at 24
      h, whereas MK-886 totally inhibited VEGF production at each time point. These
      results suggest that IL-1beta-induced mPGES-1 protein expression preferentially
      coupled with COX-2 protein at late stages of PGE2 production and that IL-1beta
      stimulated VEGF production was totally dependent on membrane-associated proteins
      involved in eicosanoid and glutathione metabolism (MAPEG) superfamily proteins,
      which includes mPGES-1, but was partially dependent on the COX-2/PGE2 pathway.

PMID- 15458924
TI  - Effects of increased intracellular cAMP on carbachol-stimulated zymogen
      activation, secretion, and injury in the pancreatic acinar cell.
AB  - A characteristic of acute pancreatitis is the premature activation and retention
      of enzymes within the pancreatic acinar cell. Because ligands linked to cAMP
      production may prevent some forms of pancreatitis, we evaluated the effects of
      increased intracellular cAMP in the rat pancreatic acinar cell. Specifically,
      this study examined the effects of the cholinergic agonist carbachol and agents
      that increase cAMP [secretin and 8-bromoadenosine 3',5'-cyclic monophosphate (8
      Br-cAMP)] on zymogen activation (trypsin and chymotrypsin), enzyme secretion, and
      cellular injury in isolated pancreatic acini. Although cAMP agonists affected the
      responses to physiological concentrations of carbachol (1 microM), their most
      prominent effects were observed with supraphysiological concentrations (1 mM).
      When secretin was added to 1 mM carbachol, there was a slight increase in zymogen
      activation, but no change in the secretion of amylase or chymotrypsin.
      Furthermore, coaddition of secretin increased parameters of cell injury (trypan
      blue exclusion, lactic dehydrogenase release, and morphological markers) compared
      with carbachol (1 mM) alone. Although directly increasing cellular cAMP by 8-Br
      cAMP caused much greater zymogen activation than carbachol (1 mM) alone or with
      secretin, 8-Br-cAMP cotreatment reduced all parameters of injury to the level of
      unstimulated acini. Furthermore, 8-Br-cAMP dramatically enhanced the secretion of
      amylase and chymotrypsin from the acinar cell. This study demonstrates that
      increasing acinar cell cAMP can overcome the inhibition of enzyme secretion
      caused by high concentrations of carbachol and eliminate acinar cell injury.

PMID- 15458925
TI  - Protection against acute pancreatitis by activation of protease-activated
      receptor-2.
AB  - Protease-activated receptor-2 (PAR-2) is a widely expressed tethered ligand
      receptor that can be activated by trypsin and other trypsin-like serine
      proteases. In the exocrine pancreas, PAR-2 activation modulates acinar cell
      secretion of digestive enzymes and duct cell ion channel function. During acute
      pancreatitis, digestive enzyme zymogens, including trypsinogen, are activated
      within the pancreas. We hypothesized that trypsin, acting via PAR-2, might
      regulate the severity of that disease, and to test this hypothesis, we examined
      the effect of either genetically deleting or pharmacologically activating PAR-2
      on the severity of secretagogue-induced experimental pancreatitis. We found that
      experimental acute pancreatitis is more severe in PAR-2(-/-) than in wild-type
      mice and that in vivo activation of PAR-2, achieved by parenteral administration
      of the PAR-2-activating peptide SLIGRL-NH2, reduces the severity of pancreatitis.
      In the pancreas during the early stages of pancreatitis, the MAPK ERK1/2 is
      activated and translocated to the nucleus, but nuclear translocation is reduced
      by activation of PAR-2. Our findings indicate that PAR-2 exerts a protective
      effect on pancreatitis and that activation of PAR-2 ameliorates pancreatitis,
      possibly by inhibiting ERK1/2 translocation to the nucleus. Our observations
      suggest that PAR-2 activation may be of therapeutic value in the treatment and/or
      prevention of severe clinical pancreatitis, and they lead us to speculate that,
      from a teleological standpoint, PAR-2 may have evolved in the pancreas as a
      protective mechanism designed to dampen the injurious effects of intrapancreatic
      trypsinogen activation.

PMID- 15458926
TI  - NF1 transcriptional factor(s) is required for basal promoter activation of the
      human intestinal NaPi-IIb cotransporter gene.
AB  - The human intestinal type IIb Na+-P(i) cotransporter (hNaPi-IIb) gene promoter
      lacks a TATA box and has a high GC content in the 5'-flanking region. To
      understand the mechanism of hNaPi-IIb gene transcription, the current study was
      performed to characterize the minimal promoter region and transcriptional
      factor(s) necessary to activate gene expression in human intestinal cells (Caco
      2). With the use of progressively shorter promoter constructs, a minimal promoter
      extending from bp -58 to +15 was identified and shown to direct high levels of
      hNaPi-IIb cotransporter expression in Caco-2 cells. Gel mobility shift assays
      (GMSAs) indicated that two regions could be bound by nuclear proteins from Caco-2
      cells: region A at bp -26/-23 and region B at bp -44/-35. The introduction of
      mutations in region A abolished promoter activity, whereas mutations in region B
      had no effect. Deletion mutants of the same regions showed identical results.
      Furthermore, DNase I footprinting experiments confirmed the observation made by
      GMSAs. Additional studies, which used a specific nuclear factor 1 (NF1)
      antiserum, demonstrated that NF1 protein(s) binds to the minimal promoter at
      region A. These results indicated that the NF1 protein(s) is required to activate
      the basal transcription of hNaPi-IIb gene under normal growth conditions. This
      study has thus identified a new target gene in the small intestinal epithelium
      that is directly regulated by NF1 transcriptional factor(s).

PMID- 15458927
TI  - Executive summary. Hormone therapy.

PMID- 15458928
TI  - Body mass index and insulin resistance.

PMID- 15458929
TI  - Breast cancer.

PMID- 15458930
TI  - Cholecystitis, biliary tract surgery, and pancreatitis.

PMID- 15458931
TI  - Cognition and dementia.

PMID- 15458932
TI  - Coronary heart disease.

PMID- 15458933
TI  - Depression.

PMID- 15458934
TI  - Genitourinary tract changes.

PMID- 15458935
TI  - Osteoarthritis.

PMID- 15458936
TI  - Osteoporosis.

PMID- 15458937
TI  - Ovarian, endometrial, and colorectal cancers.

PMID- 15458938
TI  - Sexual dysfunction.

PMID- 15458939
TI  - Skin.

PMID- 15458940
TI  - Stroke.

PMID- 15458941
TI  - Vasomotor symptoms.

PMID- 15458942
TI  - Venous thromboembolic disease.

PMID- 15458943
TI  - Summary of balancing risks and benefits.

PMID- 15458945
TI  - The alpha2-isoform of Na-K-ATPase mediates ouabain-induced hypertension in mice
      and increased vascular contractility in vitro.
AB  - Although ouabain is known to induce hypertension, the mechanism of how this
      cardiac glycoside affects blood pressure is uncertain. The present study
      demonstrates that the alpha2-isoform of the Na-K-ATPase mediates the pressor
      effects of ouabain in mice. To accomplish this, we analyzed the effect of ouabain
      on blood pressure in wild-type mice, where the alpha2-isoform is sensitive to
      ouabain, and genetically engineered mice expressing a ouabain-insensitive alpha2
      isoform of the Na-K-ATPase. Thus differences in the response to ouabain between
      these two genotypes can only be attributed to the alpha2-isoform of Na-K-ATPase.
      As the alpha1-isoform is naturally resistant to ouabain in rodents, it will not
      be inhibited by ouabain in either genotype. Whereas prolonged administration of
      ouabain increased levels of ouabain in serum from both wild-type and targeted
      animals, hypertension developed only in wild-type mice. In addition, bolus
      intravenous infusion of ouabain increased the systolic, mean arterial, and left
      ventricular blood pressure in only wild-type anesthetized mice. In vitro, ouabain
      increased vascular tone and thereby phenylephrine-induced contraction of the
      aorta in intact and endothelium-denuded wild-type mice but in alpha2-resistant
      mice. Ouabain also increased the magnitude of the spontaneous contractions of
      portal vein and the basal tone of the intact aorta from only wild-type mice. The
      increase in aortic basal tone was dependent on the presence of endothelium. Our
      studies also demonstrate that the alpha2-isoform of Na-K-ATPase mediates the
      ouabain-induced increase in vascular contractility. This could play a role in the
      development and maintenance of ouabain-induced hypertension.

PMID- 15458946
TI  - Hypercholesterolemia abolishes voltage-dependent K+ channel contribution to
      adenosine-mediated relaxation in porcine coronary arterioles.
AB  - Hypercholesterolemic patients display reduced coronary flow reserve in response
      to adenosine infusion. We previously reported that voltage-dependent K+ (Kv)
      channels contribute to adenosine-mediated relaxation of coronary arterioles
      isolated from male miniature swine. For this study, we hypothesized that
      hypercholesterolemia attenuates Kv channel contribution to adenosine-induced
      vasodilatation. Pigs were randomly assigned to a control or high fat/high
      cholesterol diet for 20-24 wk, and then killed. After completion of the
      experimental treatment, arterioles (approximately 150 microm luminal diameter)
      were isolated from the left-ventricular free wall near the apical region of the
      heart, cannulated, and pressurized at 40 mmHg. Adenosine-mediated relaxation was
      significantly attenuated in both endothelium-intact and -denuded arterioles from
      hypercholesterolemic compared with control animals. The classic Kv channel
      blocker, 4-aminopyridine (1 mM), significantly attenuated adenosine-mediated
      relaxation in arterioles isolated from control but not hypercholesterolemic
      animals. Furthermore, the nonselective K+ channel blocker, tetraethylammonium
      (TEA; 1 mM) significantly attenuated adenosine-mediated relaxation in arterioles
      from control but not hypercholesterolemic animals. In additional experiments,
      coronary arteriolar smooth muscle cells were isolated, and whole cell Kv currents
      were measured. Kv currents were significantly reduced (approximately 15%) in
      smooth muscle cells from hypercholesterolemic compared with control animals.
      Furthermore, Kv current sensitive to low concentrations of TEA was reduced
      (approximately 45%) in smooth muscle cells from hypercholesterolemic compared
      with control animals. Our data indicate that hypercholesterolemia abolishes Kv
      channel contribution to adenosine-mediated relaxation in coronary arterioles,
      which may be attributable to a reduced contribution of TEA-sensitive Kv channels
      in smooth muscle of hypercholesterolemic animals.

PMID- 15458948
TI  - Contribution of endothelin to coronary vasomotor tone is abolished after
      myocardial infarction.
AB  - Left ventricular dysfunction in swine with a recent myocardial infarction (MI) is
      associated with neurohumoral activation, including increased catecholamines and
      endothelin (ET). Although the increase in ET may serve to maintain blood pressure
      and, hence, perfusion of essential organs such as the heart and brain, it could
      also compromise myocardial perfusion by evoking coronary vasoconstriction. In the
      present study, we tested the hypothesis that endogenous ET contributes to
      perturbations in myocardial O2 balance during exercise in remodeled myocardium of
      swine with a recent MI. For this purpose, 26 chronically instrumented swine (10
      with and 16 without MI) were studied at rest and while running on a treadmill at
      1-4 km/h. After MI, plasma ET increased from 3.2 +/- 0.4 to 4.9 +/- 0.3 pM (P <
      0.05). In normal swine, blockade of ETA (by EMD-122946) or ETA-ETB (by
      tezosentan) receptors resulted in an increase in coronary venous PO2, i.e.,
      coronary vasodilation at rest, which decreased during exercise. In contrast,
      neither ETA nor ETA-ETB receptor blockade resulted in coronary vasodilation in
      swine with MI. Coronary vasoconstriction to intravenous ET-1 infusion in awake
      resting swine was blunted after MI. To investigate whether factors released by
      cardiac myocytes contributed to decreased vascular responsiveness to ET, we
      performed ET-1 dose-response curves in isolated coronary arterioles (70-200
      microm). Vasoconstriction to ET-1 in isolated arterioles from MI swine was
      enhanced. In conclusion, the vasoconstrictor influence of endogenous as well as
      exogenous ET on coronary circulation in vivo is reduced. Because the response of
      isolated coronary arterioles to ET is increased after MI, the reduced
      vasoconstrictor influence in vivo suggests modulation of ET receptor sensitivity
      by cardiac myocytes, which may serve to maintain adequate myocardial perfusion.

PMID- 15458949
TI  - Neuroendocrine properties of intrinsic cardiac adrenergic cells in fetal rat
      heart.
AB  - Intrinsic cardiac adrenergic (ICA) cells in developing rat heart constitute a
      novel adrenergic signaling system involved in cardiac regulation. Regulatory
      mechanisms of ICA cells remain to be defined. Immunohistochemical study of fetal
      rat hearts demonstrated ICA cells with catecholamine biosynthetic enzyme tyrosine
      hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT). The mRNA of
      TH and PNMP was also detected in fetal rat hearts before sympathetic innervation.
      Immunoreactivity of norepinephrine transporter (NET) was localized to ICA cells
      in rat heart tissue and primary cell culture. For the functional study, the
      activity of intracellular Ca2+ concentration ([Ca2+]i) transients was quantified
      by a ratio fluorescent spectrometer in cultured ICA cells and myocytes. ICA cells
      generated spontaneous [Ca2+]i transients that were eliminated by tetrodotoxin or
      Ca(2+)-free solutions and showed greatly reduced amplitude with the addition of L
      type Ca2+ channel blocker nifedipine. [3H]norepinephrine studies demonstrate
      release and uptake of norepinephrine. Functional interaction between
      catecholamines produced by the ICA cells and cocultured myocytes was evident by
      the effect of the beta-adrenergic blocker atenolol eliciting a dose-dependent
      reduction in the amplitude and frequency of [Ca2+]i transients of beating
      myocytes. Hypoxia inhibited [Ca2+]i transient activity of ICA cells, which
      subsequently produced a reoxygenation-mediated rebound augmentation of [Ca2+]i
      transients. We conclude that ICA cells are capable of catecholamine synthesis,
      release, and uptake. They generate spontaneous [Ca2+]i transient activity that
      can be regulated by oxygen tension. ICA cells may provide an alternative
      adrenergic supply to maintain cardiac contractile and pacemaker function at rest
      and during stress in the absence of sympathetic innervation.

PMID- 15458950
TI  - Chronic central infusion of aldosterone leads to sympathetic hyperreactivity and
      hypertension in Dahl S but not Dahl R rats.
AB  - Six-week-old Dahl salt-sensitive (S) and -resistant (R) rats received for 2 wk an
      intracerebroventricular infusion of aldosterone (Aldo) (22.5 ng/h) or vehicle
      containing artificial cerebrospinal fluid (aCSF) with 0.15 M Na+. At 8 wk, mean
      arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity
      (RSNA) were recorded in conscious rats at rest, in response to air stress, and to
      an intracerebroventricular injection of the alpha2-adrenoceptor agonists
      guanabenz or ouabain. Baroreflex control of RSNA and HR was estimated by using
      intravenous phenylephrine and nitroprusside. In Dahl S but not Dahl R rats, Aldo
      raised resting MAP by 20-25 mmHg, doubled sympathoexcitatory and pressor
      responses to air stress and sympathoinhibitory and depressor responses to
      guanabenz, and impaired baroreflex function. In Dahl S but not Dahl R rats, Aldo
      significantly increased content of ouabain-like compounds (OLC) in the
      hypothalamus and attenuated excitatory responses to ouabain. Aldo did not affect
      water intake, plasma electrolytes, or OLC in plasma and adrenal glands. In
      another set of three groups of Dahl S rats, Aldo dissolved in aCSF containing
      0.16, 0.15, or 0.14 M Na+ was infused intracerebroventricularly for 2 wk. CSF Na+
      concentration ([Na+]) showed only a nonsignificant increase, but resting MAP
      increased from 111 +/- 3 mmHg in rats with Aldo in 0.14 M Na+ to 131 +/- 3 and
      147 +/- 3 mmHg with Aldo in 0.15 and 0.16 M Na+, respectively (P < 0.05 for
      both). These findings indicate that in Dahl S rats, intracerebroventricular
      infusion of Aldo causes similar central responses as high salt intake, i.e.,
      increases in brain OLC content, sympathetic hyperreactivity, and hypertension.
      The extent of the increase in blood pressure (BP) by intracerebroventricular Aldo
      depends on the [Na+] in the vehicle. In Dahl R rats, intracerebroventricular Aldo
      did not increase brain OLC, sympathetic reactivity, and BP, suggesting that in
      this rat strain, a decrease in central responsiveness to mineralocorticoids may
      contribute to its salt-resistant nature.

PMID- 15458951
TI  - Aggregate formation of erythrocytes in postcapillary venules.
AB  - The purpose of the present study was to obtain information on erythrocyte
      aggregate formation in vivo. The movements of erythrocytes in postcapillary
      venules of the rat spinotrapezius muscle at various flow rates were recorded with
      a high-speed video camera before and after infusion of dextran 500. To
      distinguish aggregates, the following criteria were used: 1) a fixed distance (4
      microm) between the center points of two adjacent cells, 2) lack of visible
      separation between the adjacent cells, and 3) movement of the adjacent cells in
      the same direction. Without dextran 500 infusion, 11 and 5% of erythrocytes
      formed aggregates in low (33.2 +/- 28.3 s) and high pseudoshear (144.2 +/- 58.3
      s) conditions, respectively, based on the above criteria. After dextran 500
      infusion, 53% of erythrocytes satisfied the criteria in the low pseudoshear
      condition (26.5 +/- 17.0 s) and 13% of erythrocytes met the criteria in the high
      pseudoshear condition (240.0 +/- 85.9 s), indicating erythrocyte aggregation is
      strongly associated with shear rate. Approximately 90% of aggregate formation
      occurred in a short time period (0.15-0.30 s after entering the venule) in a
      region 15 to 30 microm from the entrance. The time delay may reflect rheological
      entrance conditions in the venule.

PMID- 15458952
TI  - Bone marrow-derived cells contribute to contractile dysfunction in endotoxic
      shock.
AB  - How infection precipitates depressed contractility is incompletely understood but
      may involve the immune, nervous, and endocrine systems as well as the heart
      itself. In this study, we examined the role of Toll-like receptor 4 (TLR4) in LPS
      induced myocardial contractile depression. Eighteen hours following endotoxin
      challenge, we compared contractile responses in hearts from wild-type (WT) and
      TLR4-deficient mice using modified Langendorff preparations. Unlike hearts from
      WT mice, TLR4-deficient hearts did not reveal significant contractile dysfunction
      following LPS administration, as measured by decreased responses in maximal left
      ventricular pressure, +dP/dtmax, and -dP/dtmax in ex vivo Langendorff
      preparations. These findings indicate a requirement for TLR4 in LPS-induced
      contractile depression. To determine the contribution of bone marrow-derived TLR4
      function to LPS-induced myocardial dysfunction, we generated TLR4 chimeras using
      adoptive transfer between histocompatible mouse strains: either TLR4-deficient
      mice with TLR4+/+ bone marrow-derived cells or TLR4+/+ animals lacking TLR4 in
      their hematopoietic cells. We then compared the contractile responses of
      engrafted animals after LPS challenges. Engraftment of TLR4-deficient mice with
      WT marrow restored sensitivity to the myocardial depressant effects of LPS in
      TLR4-deficient hearts (P < 0.05). Inactivation of bone marrow-derived TLR4
      function, via transplantation of WT mice with TLR4-/- marrow, however, did not
      protect against the depressant effect of endotoxin. These findings indicate that
      bone marrow-derived TLR4 activity is sufficient to confer sensitivity to mice
      lacking TLR4 in all other tissues. However, because inactivation of marrow
      derived TLR4 function alone does not protect against endotoxin-triggered
      contractile dysfunction, TLR4 function in other tissues may also contribute to
      this response.

PMID- 15458953
TI  - Contribution of the subfornical organ to angiotensin II-induced hypertension.
AB  - Previous studies clearly demonstrated acute actions of angiotensin II (ANG II) at
      one of the central circumventricular organs, the subfornical organ (SFO), but
      studies demonstrating a role for the SFO in the chronic actions of ANG II remain
      uncertain. The purpose of this study was to examine the role of the SFO in the
      chronic hypertensive phase of ANG II-induced hypertension. We hypothesized that
      the SFO is necessary for the full hypertensive response observed during the
      chronic phase of ANG II-induced hypertension. To test this hypothesis, male
      Sprague-Dawley rats were subjected to sham operation (sham rats) or electrolytic
      lesion of the SFO (SFOx rats). After 1 wk, the rats were instrumented with venous
      catheters and radiotelemetric transducers for intravenous administration of ANG
      II and measurement of blood pressure and heart rate, respectively. Rats were then
      allowed 1 wk for recovery. After 3 days of saline control infusion (7 ml of 0.9%
      NaCl/day), sham and SFOx rats were infused with ANG II at 10 ng.kg(-1).min(-1)
      i.v. for 10 consecutive days and then allowed to recover for 3 days. A 0.4% NaCl
      diet and distilled water were provided ad libitum. At day 5 of ANG II infusion,
      mean arterial pressure increased 11.7 +/- 3.0 mmHg in sham rats (n = 9) but
      increased only 3.7 +/- 1.4 mmHg in SFOx rats (n = 9). This trend continued
      through day 10 of ANG II treatment. These results support the hypothesis that the
      SFO is necessary for the full hypertensive response to chronic ANG II
      administration.

PMID- 15458954
TI  - Mitochondrial KATP channels in hindlimb remote ischemic preconditioning of
      skeletal muscle against infarction.
AB  - We previously demonstrated in the pig that instigation of three cycles of 10 min
      of occlusion and reperfusion in a hindlimb by tourniquet application
      (approximately 300 mmHg) elicited protection against ischemia-reperfusion injury
      (infarction) in multiple distant skeletal muscles subsequently subjected to 4 h
      of ischemia and 48 h of reperfusion, but the mechanism was not studied. The aim
      of this project was to test our hypothesis that mitochondrial ATP-sensitive
      potassium (KATP) (mKATP) channels play a central role in the trigger and mediator
      mechanisms of hindlimb remote ischemic preconditioning (IPC) of skeletal muscle
      against infarction in the pig. We observed in the pig that hindlimb remote IPC
      reduced the infarct size of latissimus dorsi (LD) muscle flaps (8 x 13 cm) from
      45 +/- 2% to 22 +/- 3% (n = 10; P < 0.05). The nonselective KATP channel
      inhibitor glibenclamide (0.3 mg/kg) or the selective mKATP channel inhibitor 5
      hydroxydecanoate (5-HD, 5 mg/kg), but not the selective sarcolemmal KATP (sKATP)
      channel inhibitor HMR-1098 (3 mg/kg), abolished the infarct-protective effect of
      hindlimb remote IPC in LD muscle flaps (n = 10, P < 0.05) when these drugs were
      injected intravenously at 10 min before remote IPC. In addition, intravenous
      bolus injection of glibenclamide (1 mg/kg) or 5-HD (10 mg/kg) at the end of
      hindlimb remote IPC also abolished the infarct protection in LD muscle flaps (n =
      10; P < 0.05). Furthermore, intravenous injection of the specific mKATPchannel
      opener BMS-191095 (2 mg/kg) at 10 min before 4 h of ischemia protected the LD
      muscle flap against infarction to a similar extent as hindlimb remote IPC, and
      this infarct-protective effect of BMS-191095 was abolished by intravenous bolus
      injection of 5-HD (5 mg/kg) at 10 min before or after intravenous injection of
      BMS-191095 (n = 10; P < 0.05). The infarct protective effect of BMS-191095 was
      associated with a higher muscle content of ATP at the end of 4 h of ischemia and
      a decrease in muscle neutrophilic myeloperoxidase activity at the end of 1.5 h of
      reperfusion compared with the time-matched control (n = 10, P < 0.05). These
      observations led us to conclude that mKATP channels play a central role in the
      trigger and mediator mechanisms of hindlimb remote IPC of skeletal muscle against
      infarction in the pig, and the opening of mKATP channels in ischemic skeletal
      muscle is associated with an ATP-sparing effect during sustained ischemia and
      attenuation of neutrophil accumulation during reperfusion.

PMID- 15458956
TI  - Prognostic laboratory markers of joint damage in rheumatoid arthritis.
AB  - OBJECTIVE: To investigate whether determination of a set of laboratory markers at
      baseline provides prognostic information on joint damage in hands and feet in
      rheumatoid arthritis. METHODS: 183 patients with early rheumatoid arthritis
      included in a prospective study were examined. Radiographic changes in hands and
      feet at 5 and 10 years after inclusion were evaluated (Larsen). The markers
      analysed were: erythrocyte sedimentation rate (ESR); HLA-DRB alleles typed by
      restriction fragment length polymorphism; and C reactive protein, cartilage
      oligomeric matrix protein (COMP), rheumatoid factor (RF) (IgG, IgA, and IgM
      subtypes), antibodies against cyclic citrullinated peptide (anti-CCP), and
      antibodies against interleukin 1alpha (anti-IL1alpha), analysed by immunoassays.
      Multiple linear regression with backward elimination was used to determine the
      prognostic value of the variables. RESULTS: 117/176 patients were positive for
      IgG RF, 138/176 for IgA RF, 139/176 for IgM RF, 140/176 for anti-CCP, and 40/182
      for anti-IL1alpha. After five years, ESR, the presence of IgA RF, serum COMP, and
      the presence of anti-CCP were significantly associated with more severe joint
      damage, and the presence of anti-IL1alpha with less severe joint damage. Baseline
      C reactive protein and anti-CCP predicted radiographic outcome after 10 years. A
      stronger prediction was obtained by combining the prognostic factors.
      CONCLUSIONS: Early determination of anti-CCP, IgA RF, anti-IL-1alpha, ESR, C
      reactive protein, and COMP predicted the development of joint damage in hands and
      feet in this cohort. A combination of these measures reflecting different aspects
      of the disease process should be useful for evaluating prognosis in individual
      patients with early rheumatoid arthritis.

PMID- 15458957
TI  - Assessing competencies in rheumatology.
AB  - Assessment of competencies in rheumatology is difficult, but possible, and is an
      important part of the evaluation of practising clinicians, helping to prevent
      poor performance. Competencies are currently assessed by the Royal College of
      Physicians, the General Medical Council, and the National Clinical Assessment
      Authority.

PMID- 15458958
TI  - Evidence for familial aggregation of hand, hip, and spine but not knee
      osteoarthritis in siblings with multiple joint involvement: the GARP study.
AB  - OBJECTIVE: To evaluate whether familial aggregation of osteoarthritis differs by
      joint site in a sibling pair study (GARP) of patients with osteoarthritis at
      multiple sites. SUBJECTS: White Dutch probands aged 40 to 70 years and their
      siblings with primary osteoarthritis at multiple sites. METHODS: The diagnosis of
      knee, hip, and spine osteoarthritis was based on a combination of pain or
      stiffness on most days of the previous month and osteophytes or joint space
      narrowing on x ray. Hand osteoarthritis was defined by ACR criteria. Odds ratios
      (OR) were calculated for siblings and probands sharing disease in the same
      joints. RESULTS: 191 sibling pairs were included (85% women; mean age 60 years).
      In the probands, osteoarthritis was present in spine (76%), hands (77%), knees
      (37%), and hips (26%). The most common combinations in probands were spine-hand
      (59%), spine-knee (27%), and hand-knee (25%). The OR adjusted for age, sex, and
      body mass index for siblings to be affected in the same joint sites as the
      proband were increased in osteoarthritis of the hand (OR = 4.4 (95% confidence
      interval, 2.0 to 9.5)), hip (OR = 3.9 (1.8 to 8.4)), spine (OR = 2.2 (1.0 to
      5.1)), hip-spine (OR = 4.7 (2.1 to 10.4)), and hand-hip (OR = 3.4 (1.1 to 10.4)).
      Siblings of probands with osteoarthritis in the knee did not have an increased
      likelihood of knee osteoarthritis. CONCLUSIONS: In middle aged patients with
      familial osteoarthritis at multiple sites, familial aggregation of osteoarthritis
      was most striking for hand and hip but remarkably absent for the knee.

PMID- 15458959
TI  - Raised levels of anti-glucose-6-phosphate isomerase IgG in serum and synovial
      fluid from patients with inflammatory arthritis.
AB  - BACKGROUND: In K/BxN mice, anti-glucose-6-phosphate isomerase (GPI) antibodies
      (Abs) are arthritogenic, and their transfer into naive mice induces arthritis.
      Anti-GPI Abs develop in many human patients with RA and are associated with more
      severe forms of the disease. OBJECTIVE: To elucidate the serum and synovial fluid
      (SF) anti-GPI IgG profiles among different patient groups with a variety of
      arthritides. METHODS: Blood and SF obtained concomitantly from 91 patients with
      clinically well defined arthritis were tested for concentrations of total anti
      GPI IgG, anti-GPI IgG subclasses, B lymphocyte stimulator (BLyS), and APRIL by
      ELISA. RESULTS: Anti-GPI IgG was detected in sera and SF of patients with many
      arthritic diseases, but was preferentially associated with inflammatory
      arthritis, in general, and RA, in particular. The anti-GPI IgG subclass usage was
      skewed and varied among the different arthritic disease groups. Inverse
      correlations between serum levels of BLyS and anti-GPI IgG and positive
      correlations between serum levels of APRIL and anti-GPI IgG were seen among
      immune based arthritic patients and patients with RA but not among non-immune
      based patients. No correlations were found in SF from any group of arthritic
      patients. CONCLUSION: Raised circulating anti-GPI Abs are not unique to patients
      with RA but are present in many patients with inflammatory arthritis. The
      difference in anti-GPI IgG subclass usage among disease groups may influence
      effector function and disease outcome. The inverse correlation between serum BLyS
      and anti-GPI IgG levels suggests that anti-GPI B cells may be regulated
      differently from other autoantibody producing B cells. Anti-GPI Abs may serve a
      pathogenic function in humans by promoting the maintenance of existing disease.

PMID- 15458960
TI  - Effects of infliximab treatment on insulin resistance in patients with rheumatoid
      arthritis and ankylosing spondylitis.
AB  - BACKGROUND: Tumour necrosis factor alpha (TNFalpha) may be an important mediator
      of insulin resistance. Infliximab is a chimeric monoclonal, high affinity
      antibody against the soluble and transmembrane TNFalpha, which can reduce
      markedly the biological activity of circulating and tissue TNFalpha and is used
      to treat various autoimmune disorders. OBJECTIVE: To assess the effects of
      infliximab infusions on insulin sensitivity in patients with rheumatoid arthritis
      (RA) and ankylosing spondylitis (AS). METHODS: 45 patients (28 with RA, 17 with
      AS) aged 19-74 years were studied. All patients were treated with intravenous
      infliximab. A complete biochemical profile was obtained before and after 6
      months' treatment with infliximab. The Homoeostasis Model Assessment (HOMA) Index
      was used to measure insulin resistance and the Quantitative Insulin Sensitivity
      Check Index (QUICKI) to measure insulin sensitivity. RESULTS: In the whole study
      group, no significant changes of the HOMA Index or QUICKI were seen. In the
      tertile of patients with the highest insulin resistance, a significant decrease
      of the HOMA Index and increase of the QUICKI was found (p<0.01 for both).
      CONCLUSIONS: The results suggest that infliximab treatment may have beneficial
      effects on insulin sensitivity in the most insulin resistant patients with RA and
      AS.

PMID- 15458961
TI  - E148Q is a disease-causing MEFV mutation: a phenotypic evaluation in patients
      with familial Mediterranean fever.
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is one of the periodic fever
      syndromes. It is common among Turks, Jews, Arabs, and Armenians. Several
      mutations in the MEFV gene, including E148Q, have been identified as causing this
      disease. It has been suggested that the E148Q mutation is the mildest mutation
      and some reports have questioned its disease association. OBJECTIVE: To evaluate
      the phenotypic features of the patients with E148Q mutation. SUBJECTS: 26
      patients homozygous for E148Q, 10 compound heterozygous for E148Q, and eight
      complex cases were assessed. RESULTS: Although four of the 26 patients with
      E148Q/E148Q were asymptomatic at the time of evaluation, abdominal pain was seen
      in 77% of the patients, fever in 66%, arthralgia in 50%, arthritis in 15.4%, and
      vomiting in 23.8%. Compound heterozygotes and complex cases had a higher
      frequency of abdominal pain, fever, arthralgia, arthritis, myalgia, and chest
      pain than subjects who were homozygous for E148Q, but none of these symptoms
      reached statistical significance. None of our patients had amyloidosis but two
      with E148Q/E148Q had a family history of amyloidosis and one had rapidly
      progressive glomerulonephritis secondary to vasculitis, which progressed to
      chronic renal failure. CONCLUSIONS: Patients homozygous for E148Q have a
      heterogeneous clinical presentation. Most are symptomatic and colchicine
      treatment is required in these patients.

PMID- 15458962
TI  - Large scale evidence and replication: insights from rheumatology and beyond.

PMID- 15458963
TI  - Inflammation in ankylosing spondylitis: a systematic description of the extent
      and frequency of acute spinal changes using magnetic resonance imaging.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is increasingly used to detect
      inflammation in the spine of patients with ankylosing spondylitis (AS).
      OBJECTIVES: To detect differentially the presence and extent of inflammation in
      the three spinal segments of patients with AS by MRI. METHODS: In 38 patients
      with active AS, acute spinal lesions were assessed by T(1) weighted, gadolinium
      enhanced, spin echo MRI (T(1)/Gd-DTPA) and short tau inversion recovery (STIR)
      sequences. MRI was quantified by the validated scoring system ASspiMRI-a. Acute
      spinal lesions were detected in the whole spine and in each spinal segment. One
      vertebral unit (VU) was defined as the region between two virtual lines drawn
      through the middle of each vertebral body. RESULTS: A greater number of
      inflammatory spinal lesions were found by the STIR sequence than by Gd-DTPA:
      inflammation was present in 30.6% of the VUs as assessed by STIR, compared with
      26.8% of the same VUs assessed by T(1)/Gd-DTPA. Inflammation was found more
      commonly in the thoracic spine (TS) than in the cervical (CS) or the lumbar spine
      (LS) with both techniques. When STIR was used, spinal inflammation in the CS, the
      TS, and LS was detected in 10/38 (26%), 28/38 (74%), and 9/38 (24%) patients,
      respectively. The VU T7/8 was found to be the VU most often affected by both
      techniques (27.8% by T(1)/Gd-DTPA and 34.5% by STIR). CONCLUSIONS: Spinal
      inflammation is a common manifestation in patients with AS, and appears more
      frequently in the TS. The scoring system ASspiMRI-a can be used for evaluation of
      acute spinal changes in AS.

PMID- 15458964
TI  - Moderate maternal vitamin A deficiency alters myogenic regulatory protein
      expression and perinatal organ growth in the rat.
AB  - Vitamin A deficiency is one of the most common dietary deficiencies in the
      developing world and is a major health concern where it is associated with
      increased risk of fetal and infant mortality and morbidity. Early studies in the
      rat demonstrated that, in addition to respiratory problems, neonates showed
      evidence of mobility problems in response to moderate vitamin A deficiency. This
      study investigated whether moderate deficiency of this vitamin plays a role in
      regulating key skeletal muscle regulatory pathways during development. Thirty
      female rats were fed vitamin A-moderate (VAM) or vitamin A-sufficient diets from
      weaning and throughout pregnancy. Fetal and neonatal hindlimb and muscle samples
      were collected on days 13.5, 15.5, 17.5, and 19.5 of pregnancy and 1 day
      following birth. Mothers fed the VAM diet had reduced retinol concentrations at
      all time points studied (P < 0.01), and neonates had reduced relative lung
      weights (P < 0.01). Fetal weight and survival did not differ between groups but
      neonatal survival was lower in the VAM group where neonates had increased
      relative heart weights (P < 0.05). Analysis of myogenic regulatory factor
      expression and calcineurin signaling in fetuses and neonates demonstrated
      decreased protein levels of myf5 [50% at 17.5 dg (P < 0.05)], myogenin [70% at
      birth (P < 0.001)], and myosin heavy chain fast [50% at birth (P < 0.05)] in
      response to moderate vitamin A deficiency. Overall, these changes suggest that
      vitamin A status during pregnancy may have important implications for fetal
      muscle development and subsequent muscle function in the offspring.

PMID- 15458965
TI  - Relationship between body size, Na+-K+-ATPase activity, and membrane lipid
      composition in mammal and bird kidney.
AB  - We investigated the relationship between body size, Na(+)-K(+)-ATPase molecular
      activity, and membrane lipid composition in the kidney of five mammalian and
      eight avian species ranging from 30-g mice to 280-kg cattle and 13-g zebra
      finches to 35-kg emus, respectively. Na(+)-K(+)-ATPase activity was found to be
      higher in the smaller species of both groups. In small mammals, the higher Na(+)
      K(+)-ATPase activity was primarily the result of an increase in the molecular
      activity (turnover rate) of individual enzymes, whereas in small birds the higher
      Na(+)-K(+)-ATPase activity was the result of an increased enzyme concentration.
      Phospholipids from both mammals and birds contained a relatively constant
      percentage of unsaturated fatty acids; however, phospholipids from the smaller
      species were generally more polyunsaturated, and a complementary significant
      allometric increase in monounsaturate content was observed in the larger species.
      In particular, the relative content of the highly polyunsaturated docosahexaenoic
      acid [22:6(n-3)] displayed the greatest variation with body mass, scaling with
      allometric exponents of -0.21 and -0.26 in the mammals and birds, respectively.
      This allometric variation in fatty acid composition was correlated with Na(+)
      K(+)-ATPase molecular activity in mammals, whereas in birds molecular activity
      only correlated with membrane cholesterol content. These relationships are
      discussed with respect to the metabolic intensity of different-sized animals.

PMID- 15458966
TI  - Postnatal modulation of prenatally programmed hypertension by dietary Na and ACE
      inhibition.
AB  - Adult hypertension in the rat can be programmed experimentally by changes in
      intrauterine environment. The offspring typically do not become hypertensive
      until 6 to 8 wk of age, and recent evidence suggests that renal dysfunction may
      participate in the pathogenesis. The present study was based on the hypothesis
      that the window for programming extends to the postnatal period in the rat. Adult
      hypertension was induced by maternal low-protein diet during the second half of
      gestation. After being weaned at 3 wk, the offspring were exposed to one of the
      following regimens for the subsequent 3 wk: 1) low-Na diet, 2) standard Na diet,
      3) high-Na diet, and 4) standard Na diet with enalapril. The pups were followed
      for 10 wk after discontinuation of the treatments. The brief exposure to low-Na
      diet or enalapril totally prevented the development of hypertension and the
      effect lasted throughout the observation period. The development of
      hyperreninemia, present in the standard Na group at 16 wk of age, was abolished
      in the low-Na and enalapril groups. Conversely, 3-wk exposure to high-Na diet
      increased the severity of the later hypertension and did not prevent the
      hyperreninemia. The findings suggest that there is a period of susceptibility
      during which prenatally programmed hypertension can be modulated postnatally,
      possibly coinciding with a critical stage in renal maturation.

PMID- 15458967
TI  - Transcriptional regulation of TNF-alpha production in neutropenia.
AB  - Neutropenia has been shown to markedly increase plasma TNF-alpha concentration
      after LPS injection and to enhance LPS-induced mortality. Experiments reported
      here demonstrate that the 15-fold higher plasma TNF-alpha concentration elicited
      by LPS in neutropenic vs. nonneutropenic unanesthetized mice correlated with
      increased hepatic and splenic, but not pulmonary, TNF-alpha mRNA. Core 2 beta-1,6
      N-acetylglucosaminyltransferase-null and CD18-deficient mice also exhibited
      exaggerated plasma TNF-alpha responses to LPS injection. Findings suggest that
      extravasated neutrophils inhibit systemic TNF-alpha production and that they do
      so through organ-selective mechanisms involving CD18 integrin and selectin
      binding.

PMID- 15458968
TI  - Effects of acupuncture on vasopressin-induced emesis in conscious dogs.
AB  - Although acupuncture has a significant clinical benefit, the mechanism of
      acupuncture remains unclear. Vasopressin, a posterior pituitary hormone, is
      involved in nausea and vomiting in humans and dogs. To investigate the antiemetic
      effects of acupuncture on vasopressin-induced emesis, gastroduodenal motor
      activity and the frequency of retching and vomiting were simultaneously recorded
      in conscious dogs. In seven dogs, four force transducers were implanted on the
      serosal surfaces of the gastric body, antrum, pylorus, and duodenum.
      Gastroduodenal motility was continuously monitored throughout the experiment.
      Vasopressin was intravenously infused at a dose of 0.1 U x kg(-1) x min(-1) for
      20 min. Electroacupuncture (EA, 1-30 Hz) at pericardium-6 (PC6), bladder-21
      (BL21), or stomach-36 (ST36) was performed before, during, and after the
      vasopressin infusion. To investigate whether the opioid pathway is involved in EA
      induced antiemetic effects, naloxone (a central and peripheral opioid receptor
      antagonist) or naloxone methiodide (a peripheral opioid receptor antagonist) was
      administered before, during, and after EA and vasopressin infusion. Intravenous
      infusion of vasopressin induced retching and vomiting in all dogs tested.
      Retrograde peristaltic contractions occurred before the onset of retching and
      vomiting. EA (10 Hz) at PC6 significantly reduced the number of episodes of
      retching and vomiting. EA at PC6 also suppressed retrograde peristaltic
      contractions. In contrast, EA at BL21 or ST36 had no antiemetic effects. The
      antiemetic effect of EA was abolished by pretreatment with naloxone but not
      naloxone methiodide. It is suggested that the antiemetic effect of acupuncture is
      mediated via the central opioid pathway.

PMID- 15458969
TI  - Effects of water deprivation and rehydration on c-Fos and FosB staining in the
      rat supraoptic nucleus and lamina terminalis region.
AB  - We studied cFos and FosB staining in the supraoptic nucleus (SON) the organum
      vasculosum of the lamina terminalis (OVLT) and the median preoptic nucleus (MnPO)
      in adult male rats after water deprivation (24 h, n = 11; 48 h, n = 12) and water
      deprivation with rehydration (22 h + water, n = 11; 46 h + water, n = 10).
      Control rats (n = 15) had water available ad libitum. Separate sets of serial
      sections from each brain were processed for immunocytochemistry using primary
      antibodies against either c-Fos or FosB protein. Plasma osmolality, vasopressin,
      hematocrit, and plasma proteins were measured in separate groups (n = 6-7). The
      number of c-Fos-positive cells in the SON was significantly increased after 24
      and 48 h of water deprivation. In contrast, rehydrated groups were not different
      from control. Water deprivation significantly increased c-Fos staining in both
      the OVLT and the MnPO, but c-Fos staining was not altered by rehydration. FosB
      staining in the SON was significantly increased only by 48-h water deprivation,
      and this effect was significantly decreased by rehydration. In the MnPO and OVLT,
      FosB staining was significantly increased by water deprivation, and, like c-Fos
      staining, these increases were not affected by rehydration. Water deprivation
      significantly increased osmolality and hematocrit, as well as plasma protein and
      vasopressin concentrations. Plasma measurements from rehydrated rats were not
      different from control. We conclude that water deprivation and rehydration
      differentially affect c-Fos and FosB staining in a region-dependent manner.

PMID- 15458970
TI  - Effect of 3beta-hydroxysteroid dehydrogenase inhibition by trilostane on blood
      pressure in the Dahl salt-sensitive rat.
AB  - The brains of rats and humans express the enzymes required for the synthesis of
      aldosterone from cholesterol, including the 3beta-steroid dehydrogenase that
      catalyzes the conversion of pregnenolone to progesterone in the pathway of
      adrenal steroid synthesis. Salt-induced hypertension in the Dahl inbred salt
      sensitive (SS/jr) rat is associated with normal to low levels of circulating
      aldosterone, yet it is abrogated by the central infusion of mineralocorticoid
      receptor antagonists. To test the hypothesis that de novo synthesis of
      aldosterone in the brain has a pathophysiological role in the salt-induced
      hypertension of the SS rat, the 3beta-steroid dehydrogenase antagonist trilostane
      was infused continuously intracerebroventricularly or subcutaneously in two
      different cohorts of Dahl SS/jr rats, one female, the other male, during and
      after the development of salt-induced hypertension. The doses of trilostane used
      had no effect on blood pressure when infused subcutaneously. Animals receiving
      vehicle intracerebroventricularly experienced a 30- to 45-mmHg increase in
      systolic blood pressure measured by tail cuff. The intracerebroventricular, but
      not subcutaneous, infusion of 0.3 microg/h trilostane effectively blocked the
      increase in systolic blood pressure and reversed the hypertension produced by
      drinking 0.9% saline. Trilostane was equally effective in female and male rats.
      Weight gain, serum aldosterone and corticosterone concentrations, and behavior
      assessed subjectively and by elevated plus maze were unchanged by the trilostane
      treatment. These studies suggest that the synthesis in the brain of a
      mineralocorticoid receptor agonist, probably aldosterone, is responsible in part
      for the salt-induced hypertension of the inbred Dahl SS/jr rat.

PMID- 15458971
TI  - Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not
      their spatial relationship with nerves.
AB  - A spatial association between mast cells and nerves has been described in both
      the gastrointestinal and genitourinary tracts. However, the factors that
      influence the anatomic relationship between mast cells and nerves have not been
      completely defined. It has been suggested that the high-affinity receptor for
      substance P [neurokinin-1 (NK1)] might modulate this interaction. We therefore
      assessed mast cell-nerve relationships in tissues isolated from wild-type and NK1
      receptor knockout (NK1-/-) mice. We now report that, in the complete absence of
      NK1 receptor expression, there is a significant increase in the number of mast
      cells without a change in the anatomic relationship between mast cell and nerves
      in stomach and bladder tissues at the light microscopic level. We next determined
      whether transplanted mast cells would maintain their spatial distribution,
      number, and contact with nerve elements. For this purpose, mast cell-deficient
      Kit(W)/Kit(W-v) mice were reconstituted with wild-type or NK1-/- bone marrow. No
      differences in mast cell-nerve contact were observed. These results suggest that
      NK1 receptor expression is important in the regulation of the number of mast
      cells but is not important in the interaction between mast cells and nerves.
      Furthermore, the interaction between mast cells and nerves is not mediated
      through NK1 receptor expression on the mast cell. Further studies are needed to
      determine the molecular pathway involved in mast cell migration and interaction
      with nerve elements, but the model of reconstitution of Kit(W)/Kit(W-v) mice with
      mast cells derived from different genetically engineered mice is a useful
      approach to further explore these mechanisms.

PMID- 15458972
TI  - Depression of cell metabolism and proliferation by membrane-permeable and 
      impermeable modulators: role for AMP-to-ATP ratio.
AB  - The metabolic and developmental depression commonly observed during natural
      states of dormancy, such as diapause and quiescence, is typically accompanied by
      an increase in the intracellular ratio of AMP to ATP. We investigated the impact
      of artificially increasing the AMP-to-ATP ratio in mouse macrophages. Evidence is
      presented here that the P2X7 receptor channel can be used as an effective means
      to load cells with membrane-impermeable compounds. Intracellular loading of
      adenosine-5'-O-thiomonophosphate (AMPS), a nonhydrolyzable analog of 5'-AMP and
      potent activator of AMP-activated protein kinase, significantly depresses
      metabolism and proliferation of macrophages. The intracellular effective AMP-to
      ATP ratio obtained (the sum of AMPS plus endogenous 5'-AMP) was 0.073, well above
      that reported to activate AMP-activated protein kinase in vitro. Optimizing both
      the conditions under which the P2X7 receptor channel is opened and the duration
      of opening facilitates high analog uptake and approximately 98% survivorship. An
      advantage to AMPS is its minimal impact on other components of the nucleotide
      pool, most notably the unchanged concentration of ADP. An alternative way to
      shift the effective AMP-to-ATP ratio is by incubation with the membrane-permeable
      compound 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), which is
      phosphorylated intracellularly to form the 5'-AMP analog ZMP. Despite a rapid
      intracellular accumulation of AICAR, conversion to ZMP was slow and inefficient.
      Furthermore, AICAR incubation increased cellular ADP, and, although cell
      proliferation was depressed, the overall cellular energy flow was unchanged. The
      rapid action of AMPS avoids upregulation of compensatory metabolic pathways and
      may provide a viable approach for promoting cell stasis.

PMID- 15458973
TI  - Restraint stress delays solid gastric emptying via a central CRF and peripheral
      sympathetic neuron in rats.
AB  - Central corticotropin-releasing factor (CRF) delays gastric emptying through the
      autonomic nervous system. CRF plays an important role in mediating delayed
      gastric emptying induced by stress. However, it is not clear whether a
      sympathetic or parasympathetic pathway is involved in the mechanism of central
      CRF-induced inhibition of solid gastric emptying. The purpose of this study was
      to investigate whether 1) CRF inhibits solid gastric emptying via a peripheral
      sympathetic pathway and 2) stress-induced inhibition of solid gastric emptying is
      mediated via a central CRF and peripheral sympathetic pathways. Using male
      Sprague-Dawley rats, CRF was injected intracisternally with or without various
      adrenergic-blocking agents. To investigate whether central CRF-induced inhibition
      of solid gastric emptying is mediated via a peripheral sympathetic pathway, rats
      underwent celiac ganglionectomy 1 wk before the gastric emptying study. After
      solid meal ingestion (90 min), gastric emptying was calculated. To investigate
      the role of endogenous CRF in stress-induced delayed gastric emptying, a CRF
      type2 receptor antagonist, astressin2-B, was intracisternally administered. Rats
      were subjected to a restraint stress immediately after the feeding.
      Intracisternal injection of CRF (0.1-1.0 microg) dose-dependently inhibited solid
      gastric emptying. The inhibitory effect of CRF on solid gastric emptying was
      significantly blocked by guanethidine, propranolol, and celiac ganglionectomy but
      not by phentolamine. Restraint stress significantly delayed solid gastric
      emptying, which was improved by astressin2-B, guanethidine, and celiac
      ganglionectomy. Our research suggests that restraint stress inhibits solid
      gastric emptying via a central CRF type2 receptor and peripheral sympathetic
      neural pathway in rats.

PMID- 15458974
TI  - 7-ketocholesterol induces protein ubiquitination, myelin figure formation, and
      light chain 3 processing in vascular smooth muscle cells.
AB  - OBJECTIVE: Oxysterols such as 7-ketocholesterol (7-KC) are important mediators of
      cell death in atherosclerosis. Therefore, in vitro studies of human smooth muscle
      cell (SMC) death in response to 7-KC were undertaken to investigate the potential
      mechanisms. METHODS AND RESULTS: Human aortic SMCs treated with 7-KC showed
      enhanced immunoreactivity for the oxidative stress marker 4-hydroxy-2-nonenal and
      upregulated several stress genes (70-kDa heat shock protein 1, heme oxygenase 1,
      and growth arrest and DNA damage-inducible protein 153) at the mRNA but not at
      the protein level. 7-KC-treated SMCs rapidly underwent cell death as determined
      by neutral red, counting of adherent cells, and depolarization of the
      mitochondrial inner membrane. Cell death was associated with upregulation of
      ubiquitin mRNA and ubiquitination of cellular proteins. Inhibition of the
      proteasome by lactacystin potentiated considerably the toxicity of 7-KC.
      Transmission electron microscopy revealed formation of myelin figures, extensive
      vacuolization, and depletion of organelles. Formation of autophagosomes was
      suggested by labeling cells with LysoTracker and monitoring processing of
      microtubule-associated protein 1 light chain 3 (LC3). Analogous to our in vitro
      studies, human atherosclerotic plaques showed signs of ubiquitination in SMCs.
      CONCLUSIONS: 7-KC activates the ubiquitin-proteasome system and induces a complex
      mode of cell death associated with myelin figure formation and processing of LC3
      evocating autophagic processes.

PMID- 15458975
TI  - Insulin resistance is independently associated with postprandial alterations of
      triglyceride-rich lipoproteins in type 2 diabetes mellitus.
AB  - OBJECTIVE: To evaluate the role of insulin resistance in development of
      postprandial dyslipidemia in type 2 diabetic patients in an experimental setting
      in which these patients were compared with nondiabetic subjects at similar
      glucose and insulin blood levels. METHODS AND RESULTS: Eight type 2 diabetic
      patients in optimal blood glucose control and 7 control subjects (aged 50.0+/-2.6
      and 48.1+/-1.3 years; body mass index 28.3+/-1.2 and 25.6+/-1.1 kg/m2; fasting
      plasma triglycerides 1.12+/-0.13 and 0.87+/-0.08 mmol/L, respectively; mean+/
      SEM; NS) consumed a mixed meal during an 8-hour hyperinsulinemic glycemic clamp.
      Mean blood glucose during clamp was approximately 7.8 mmol/L, and plasma insulin
      during the preprandial steady state was approximately 480 pmol/L in both groups,
      that differed for insulin sensitivity (M/I value lower in diabetic subjects
      [1.65+/-0.30 and 3.42+/-0.60; P<0.05]). Subjects with diabetes had higher
      postprandial levels of lipids and apolipoprotein B (apoB) in large very low
      density lipoprotein (incremental area for triglycerides 1814+/-421 versus 549+/
      153 micromol/Lx6 hours; P<0.05; cholesterol 694+/-167 versus 226+/-41
      micromol/Lx6 hours; P<0.05; apoB-48 6.3+/-1.0 versus 2.6+/-0.7 mg/Lx6 hours;
      P<0.05; apoB-100 56.5+/-14.9 versus 26.2+/-11.0 mg/Lx6 hours; NS). Basal
      lipoprotein lipase (LPL) activity before and after meal was higher in diabetic
      subjects, whereas postheparin LPL activity 6 hours after the meal was similar.
      CONCLUSIONS: Insulin resistance is also associated with postprandial lipoprotein
      abnormalities in type 2 diabetes after acute correction for hyperglycemia and
      hyperinsulinemia.

PMID- 15458976
TI  - Promotion of leukocyte adhesion by a novel interaction between vitronectin and
      the beta2 integrin Mac-1 (alphaMbeta2, CD11b/CD18).
AB  - OBJECTIVE: The leukocyte integrin Mac-1 (alphaMbeta2, CD11b/CD18) binds a number
      of ligands and counter-receptors and thereby is a major determinant in regulation
      of leukocyte adhesion and extravasation. Vitronectin (VN) is an adhesion
      promoting factor that is abundantly present as matrix molecule in vascular
      diseases such as atherosclerosis. Until now, only an indirect interaction between
      Mac-1 and VN via the urokinase receptor (urokinase plasminogen activator
      receptor) was known. We now propose that Mac-1 and VN can directly interact with
      each other. METHODS AND RESULTS: In an in vitro system with purified components,
      Mac-1 specifically bound the multimeric matrix form of VN but not the monomeric
      plasma form. Using various competitors, the interaction domains in Mac-1 and VN
      were localized. Mac-1-expressing but not untransfected Chinese hamster ovary
      cells adhered strongly on VN. Introduction of a GFFKR deletion in the alphaM
      subunit of Mac-1, which increases the constitutive activation of the integrin,
      led to increased adhesion on VN. Peripheral human blood neutrophils adhered and
      migrated on multimeric VN in a Mac-1-dependent manner. CONCLUSIONS: These results
      show that there is a specific integrin-affinity-regulated interaction between Mac
      1 and the matrix form but not the plasma form of VN that may significantly
      participate in leukocyte adhesion and extravasation.

PMID- 15458977
TI  - Induction of the paraoxonase-1 gene expression by resveratrol.
AB  - OBJECTIVE: The human paraoxonase-1 (PON-1) is a high-density lipoprotein
      associated enzyme, mainly secreted by the liver, that displays protective
      properties toward cardiovascular disease and organophosphate intoxication.
      Resveratrol is a polyphenolic phytoalexin found in grapes and wine and is thought
      to display cardioprotective effects. It is able to interact with transcriptional
      modulators such as the estrogen receptor alpha (ERalpha). We investigated the
      effect of resveratrol on the PON-1 gene expression. METHODS AND RESULTS: PON-1
      activity assays, Northern blot, and transfection experiments showed that
      resveratrol increased the PON-1 gene expression in human hepatocyte primary
      cultures and in the HuH7 hepatoma cell line involving a transcriptional
      mechanism. The resveratrol effect was not ERalpha-dependent and was surprisingly
      mediated by the aryl hydrocarbon receptor (AhR) and an unconventional AhR
      responsive element in the PON-1 gene promoter. This agonist effect of resveratrol
      was specific for this DNA motif and was not observed on classical AhR responsive
      elements. CONCLUSIONS: These observations suggest that the PON-1 gene induction
      may be involved in the cardioprotective properties of resveratrol. They also
      highlight a ligand-dependent differential modulation of AhR-sensitive genes.

PMID- 15458978
TI  - Inhibition of endogenous leptin protects mice from arterial and venous
      thrombosis.
AB  - OBJECTIVE: Human obesity is associated with an increased risk for arterial and
      venous thrombosis and with elevated levels of leptin in the blood. Leptin
      administration promotes arterial thrombosis in mice, and leptin-deficient ob/ob
      mice have an attenuated thrombotic response to injury. Thus, endogenous leptin
      may regulate arterial and venous thrombosis in vivo. Experiments were performed
      to test this hypothesis. METHODS AND RESULTS: A leptin-neutralizing antibody was
      administered intravenously into wild-type mice 15 minutes before carotid artery
      injury with ferric chloride. The antibody-treated mice demonstrated prolonged
      times to thrombotic occlusion and formed unstable, embolizing thrombi. Thus,
      inhibiting leptin converted the thrombotic phenotype of wild-type mice into one
      that closely resembled that of ob/ob mice. The effect of leptin inhibition on
      venous thrombosis and pulmonary embolism was also investigated. Injection of a
      mixture of collagen and epinephrine into the jugular vein induced fatal pulmonary
      embolism in >90% of the control wild-type mice but in <40% of their antibody
      treated counterparts. Histological analysis revealed that the antibody
      significantly reduced the number of occlusive thrombi in the pulmonary vessels.
      CONCLUSIONS: Inhibition of circulating leptin protects against arterial and
      venous thrombosis in mice and possibly in hyperleptinemic obese individuals.

PMID- 15458979
TI  - Differential expression patterns of proinflammatory and antiinflammatory
      mediators during atherogenesis in mice.
AB  - OBJECTIVE: Recent advances support the current view of atherosclerosis as an
      inflammatory process that initiates and promotes lesion development to the point
      of acute thrombotic complications and clinical events. ApoE-deficient mice are a
      valuable model for studying the involvement of inflammatory mediators during
      atherogenesis. In this study, we investigated the correlation between
      atherosclerotic plaque development and expression of important pro- and
      antiinflammatory mediators during progression of atherosclerosis in ApoE-/- mice.
      METHODS AND RESULTS: Expression of proinflammatory cytokines, chemokines, and
      chemokine receptors within aortic lesions increased during atherogenesis, as
      detected by real-time quantitative reverse-transcription polymerase chain
      reaction. In parallel, the number of inflammatory cells within lesions increased
      together with serum cholesterol and body weight. Interestingly, the majority of
      inflammatory mediators investigated reached their maximum expression values at 10
      weeks of diet, followed by continuous decrease of their expression levels,
      whereas atherosclerotic plaque size further increased. We show that the
      expression pattern of these different inflammatory mediators mainly correlates
      with the amount of inflammatory cells present within the atherosclerotic lesions.
      CONCLUSIONS: Atherosclerosis might result from an imbalance between pro- and
      antiinflammatory mediators in response to endothelial injury induced by
      cholesterol-rich diet. These data provide important information on the expression
      kinetics of inflammatory mediators and point out the possible role of
      antiinflammatory cells during atherogenesis.

PMID- 15458980
TI  - Interaction of monocytes with vascular smooth muscle cells regulates monocyte
      survival and differentiation through distinct pathways.
AB  - OBJECTIVE: Vascular smooth muscle cells (VSMCs) may regulate monocyte functions
      within atherosclerotic lesions. We investigated the impact of VSMC/monocyte
      interactions on monocyte apoptosis and scavenger receptor CD36 expression, key
      events related to monocyte survival and differentiation. METHODS AND RESULTS:
      Serum deprivation significantly increased THP-1 and human peripheral blood
      monocyte apoptosis. However, this was significantly reversed by physical binding
      to human VSMCs (HVSMCs). On binding to HVSMCs, antiapoptotic kinase Akt and its
      downstream targets were phosphorylated, and Bcl-2 expression was enhanced.
      Binding-mediated suppression of apoptosis and Akt phosphorylation were attenuated
      by a phosphoinositide 3-kinase inhibitor and also by an antibody to vascular cell
      adhesion molecule-1. CD36 expression was also significantly increased in THP-1
      cells and in human peripheral blood monocytes after binding to HVSMCs, and this
      was mediated by both direct contact and soluble factors. Extracellular signal
      regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase phosphorylation
      was increased in THP-1 cells after HVSMC coculture. Furthermore, an ERK1/2
      inhibitor blocked monocyte CD36 upregulation. Contact-dependent CD36 induction
      and ERK1/2 phosphorylation in monocytes were inhibited by blocking vascular cell
      adhesion molecule-1 on HVSMC, whereas soluble factor-induced CD36 expression was
      attenuated by a monocyte chemoattractant protein-1 neutralizing antibody.
      CONCLUSIONS: These data provide evidence of novel VSMC-dependent local regulation
      mechanisms for monocyte survival and differentiation in atherosclerosis.

PMID- 15458981
TI  - Quantification and 3D reconstruction of atherosclerotic plaque components in
      apolipoprotein E knockout mice using ex vivo high-resolution MRI.
AB  - OBJECTIVE: To investigate the ability of high-resolution MRI to determine
      composition and microanatomy of atherosclerosis in mouse aortic root and
      brachiocephalic artery. METHODS AND RESULTS: Aortic root and brachiocephalic
      arteries of apolipoprotein E knockout (apoE-/-) mice fed Western diet for 10, 20,
      or 30 weeks were imaged ex vivo (11.7 T; 3D multiecho sequence; resolution
      47x47x62.5 microm). Using semiautomated histogram-based methods, MRI accurately
      quantified lipid-rich/necrotic areas in the aortic root (r2=0.84; P<0.001) and
      brachiocephalic artery (r2=0.90; P<0.001) compared with histology. Similarly,
      cell-rich caps in aortic roots, quantified by MRI and histology, correlated
      closely (r2=0.74; P<0.001). Reconstruction of segmented brachiocephalic arteries
      in 3D provided unique insights into plaque microanatomy and enabled volumetric
      quantification of plaque and lipid-rich/necrotic core. Between 10 and 30 weeks,
      3D measurement identified an 11.6-fold increase in plaque volume (versus 4.1-fold
      for 2D) and a 21.3-fold increase in plaque lipid-rich/necrotic core volume
      (versus 6.4-fold for 2D), indicating superior power of 3D quantification.
      CONCLUSIONS: Ex-vivo high-resolution 3D MRI accurately quantified lipid
      rich/necrotic core and cell-rich cap areas in atherosclerotic lesions in apoE-/-
      mice. Reconstruction and volumetric quantification of segmented brachiocephalic
      arteries demonstrated greater sensitivity in detecting changes in plaque size and
      lipid composition over time than 2D analysis.

PMID- 15458982
TI  - Differential effects of vasodilatory prostaglandins on focal adhesions,
      cytoskeletal architecture, and migration in human aortic smooth muscle cells.
AB  - OBJECTIVE: Cyclooxygenases 1 and 2 are expressed in atherosclerotic arteries, and
      local generation of prostacyclin and prostaglandin E2 (PGE2) occurs. However, the
      role of cyclooxygenases and individual prostaglandins during plaque progression
      is currently uncertain. The present study characterizes the effect of
      vasodilatory prostaglandins on morphology, focal adhesion (FA) function, and
      migration in human aortic smooth muscle cells (SMCs). METHODS AND RESULTS: The
      stable prostacyclin analog iloprost transiently induced: (1) disassembly of FA
      and stress fibers, (2) partial retraction and rounding of SMCs, (3)
      hypophosphorylation of FA kinase (FAK) and paxillin, and (4) inhibition of
      platelet-derived growth factor-BB-induced migration. Inhibition of FAK
      phosphorylation and morphological changes were mimicked by forskolin, inhibited
      by H89, and prevented by the protein tyrosine phosphatase inhibitor vanadate and
      by calpeptin. PGE2 was by far less efficient with respect to all parameters
      investigated. This difference correlated with the respective cAMP induction in
      response to iloprost and PGE2. CONCLUSIONS: Inhibition of FAK phosphorylation and
      FA function is a new target of vasodilatory prostaglandins, which might be
      causally involved in the antimigratory effects of prostaglandins. Importantly,
      prostacyclin analogs and PGE2 differ dramatically with respect to
      dephosphorylation of FAK and inhibition of migration, which might be of relevance
      for their respective functions in atherosclerosis.

PMID- 15458983
TI  - Using shared genomic synteny and shared protein functions to enhance the
      identification of orthologous gene pairs.
AB  - MOTIVATION: The identification of orthologous gene pairs is generally based on
      sequence similarity. Gene pairs that are mutually 'best hits' between the genomes
      being compared are asserted to be orthologs. Although this method identifies most
      orthologous gene pairs with high confidence, it will miss a fraction of them,
      especially genes in duplicated gene families. In addition, the approach depends
      heavily on the completeness and quality of gene annotation. When the gene
      sequences are not correctly represented the approach is unlikely to find the
      correct ortholog. To overcome these limitations, we have developed an approach to
      identify orthologous gene pairs using shared chromosomal synteny and the
      annotation of protein function. RESULTS: Assembled mouse and human genomes were
      used to identify the regions of conserved synteny between these genomes.
      'Syntenic anchors' are conserved non-repetitive locations between mouse and human
      genomes. Using these anchors, we identified blocks of sequences that contain
      consistently ordered anchors between the two genomes (syntenic blocks). The
      synteny information has been used to help us identify orthologous gene pairs
      between mouse and human genomes. The approach combines the mutual selection of
      the best tBlastX hits between human and mouse transcripts, and inferring gene
      orthologous relationships based on sharing syntenic anchors, collocating in the
      same syntenic blocks and sharing the same annotated protein function. Using this
      approach, we were able to find 19,357 orthologous gene pairs between human and
      mouse genomes, a 20% increase in the number of orthologs identified by
      conventional approaches.

PMID- 15458984
TI  - Biological sequence analysis through the one-dimensional percolation transform
      and its enhanced version.
AB  - MOTIVATION: The necessity to characterize the spatial uniformity (or lack of it)
      of symbols in biological sequences, given its implications for identification of
      the properties of the structures associated with the sequences. METHODS: A one
      dimensional version of a recently introduced percolation-based approach is
      presented, which allows the accurate quantification of symbol distributions even
      in the presence of co-existing densities. An enhanced version of this
      methodology, which uses an agglomerative process to organize hierarchically the
      sequence into subsequences, is also proposed and illustrated. 3. RESULTS: The
      potential of the proposed methodology is illustrated with respect to synthetic
      and real data (1881 zebrafish and 1200 Xenopus proteins) and compared to two
      alternative multiscale methodologies, with encouraging results including the
      possibility to identify particularly remarkable amino acid arrangements in
      proteins. 4. CONTACT: luciano@if.sc.usp.br.

PMID- 15458985
TI  - Protecting the human rights of people with mental disorder: new recommendations
      emerging from the Council of Europe.

PMID- 15458986
TI  - A decade of the Social, Genetic and Developmental Psychiatry Centre at the
      Institute of Psychiatry.

PMID- 15458987
TI  - Components of a modern mental health service: a pragmatic balance of community
      and hospital care: overview of systematic evidence.
AB  - BACKGROUND: There is controversy about whether mental health services should be
      provided in community or hospital settings. There is no worldwide consensus on
      which mental health service models are appropriate in low-, medium- and high
      resource areas. AIMS: To provide an evidence base for this debate, and present a
      stepped care model. METHOD: Cochrane systematic reviews and other reviews were
      summarised. RESULTS: The evidence supports a balanced approach, including both
      community and hospital services. Areas with low levels of resources may focus on
      improving primary care, with specialist back-up. Areas with medium resources may
      additionally provide out-patient clinics, community mental health teams (CMHTs),
      acute in-patient care, community residential care and forms of employment and
      occupation. High-resource areas may provide all the above, together with more
      specialised services such as specialised out-patient clinics and CMHTs, assertive
      community treatment teams, early intervention teams, alternatives to acute in
      patient care, alternative types of community residential care and alternative
      occupation and rehabilitation. CONCLUSIONS: Both community and hospital services
      are necessary in all areas regardless of their level of resources, according to
      the additive and sequential stepped care model described here.

PMID- 15458988
TI  - Cognitive therapy for the prevention of psychosis in people at ultra-high risk:
      randomised controlled trial.
AB  - BACKGROUND: Advances in the ability to identify people at high risk of developing
      psychosis have generated interest in the possibility of preventing psychosis.
      AIMS: To evaluate the efficacy of cognitive therapy for the prevention of
      transition to psychosis. METHOD: A randomised controlled trial compared cognitive
      therapy with treatment as usual in 58 patients at ultra-high risk of developing a
      first episode of psychosis. Therapy was provided over 6 months, and all patients
      were monitored on a monthly basis for 12 months. RESULTS: Logistic regression
      demonstrated that cognitive therapy significantly reduced the likelihood of
      making progression to psychosis as defined on the Positive and Negative Syndrome
      Scale over 12 months. In addition, it significantly reduced the likelihood of
      being prescribed antipsychotic medication and of meeting criteria for a DSM-IV
      diagnosis of a psychotic disorder. Analysis of covariance showed that the
      intervention also significantly improved positive symptoms of psychosis in this
      population over the 12-month period CONCLUSIONS: Cognitive therapy appears to be
      an acceptable and efficacious intervention for people at high risk of developing
      psychosis.

PMID- 15458989
TI  - Prevalence and correlates of self-reported psychotic symptoms in the British
      population.
AB  - BACKGROUND: The psychosis phenotype is generally thought of as a categorical
      entity. However, there is increasing evidence that psychosis exists in the
      population as a continuum of severity rather than an all-or-none phenomenon.
      AIMS: To investigate the prevalence and correlates of self-reported psychotic
      symptoms using data from the 2000 British National Survey of Psychiatric
      Morbidity. METHOD: A total of 8580 respondents aged 16-74 years were interviewed.
      Questions covered mental health, physical health, substance use, life events and
      socio-demographic variables. The Psychosis Screening Questionnaire (PSQ) was used
      to identify psychotic symptoms. RESULTS: Of the respondents, 5.5% endorsed one or
      more items on the PSQ. Factors independently associated with psychotic symptoms
      were cannabis dependence, alcohol dependence, victimisation, recent stressful
      life events, lower intellectual ability and neurotic symptoms. Male gender was
      associated with paranoid thoughts, whereas female gender predicted hallucinatory
      experiences. CONCLUSIONS: Self-reported psychotic symptoms are less common in
      this study than reported elsewhere, because of the measure used. These symptoms
      have demographic and clinical correlates similar to clinical psychosis.

PMID- 15458990
TI  - Characteristics of teams, staff and patients: associations with outcomes of
      patients in assertive outreach.
AB  - BACKGROUND: Little is known about what characteristics of teams, staff and
      patients are associated with a favourable outcome of severe mental illness
      managed by assertive outreach. AIMS: To identify predictors of voluntary and
      compulsory admissions in routine assertive outreach services in the UK. METHOD:
      Nine features of team organisation and policy, five variables assessing staff
      satisfaction and burn-out and eleven patient characteristics taken from the
      baseline data of the Pan-London Assertive Outreach Study were tested as
      predictors of voluntary and compulsory admissions within a 9-month follow-up
      period. RESULTS: Weekend working, staff burn-out and lack of contact of the
      patient with out and lack of contact of the patient with other services were
      associated independently with a higher probability of both voluntary and
      compulsory admission. In addition, admissions in the past predicted further
      voluntary and compulsory admissions, and teams not working extended hours
      predicted compulsory admissions in the follow-up period. CONCLUSIONS:
      Characteristics of team working practice, staff burn-out and patients' history
      are associated independently with outcome. Patient contact with other services is
      a positive prognostic factor.

PMID- 15458991
TI  - Anorexia nervosa among female secondary school students in Ghana.
AB  - BACKGROUND: We set out to determine whether anorexia nervosa exists in a culture
      where the pressure to be thin is less pervasive. AIMS: To determine whether there
      were any cases of anorexia nervosa in female students attending two secondary
      schools in the north-east region of Ghana. METHOD: The body mass index (BMI) of
      consenting students was calculated after measuring their height and weight. Those
      with a BMI </=19 kg/m(2) underwent a structured clinical assessment including
      mental state, physical examination and completion of the Eating Attitudes Test
      and the Bulimic Investigatory Test, Edinburgh. Participants nominated a best
      friend to serve as a comparison group, and these young women under went the same
      assessments. RESULTS: Of the 668 students who were screened for BMI, 10 with a
      BMI <17.5 kg/m(2) appeared to have self-starvation as the only cause of their low
      weight. All 10 viewed their food restriction positively and in religious terms.
      The beliefs of these individuals included ideas of self-control and denial of
      hunger, without the typical anorexic concerns about weight or shape. CONCLUSIONS:
      Morbid self-starvation may be the core feature of anorexia nervosa, with the
      attribution for the self-starvation behaviour varying between cultures.

PMID- 15458992
TI  - Needs for mental health treatment among general practice attenders.
AB  - BACKGROUND: No study has directly assessed the need for mental health care among
      those consulting in general practice. AIMS: To make a direct assessment of the
      needs for mental health care in people with non-psychotic disorders consulting
      their general practitioner. METHOD: In a two-phase study design, consecutive
      general practice attenders aged 17-65 years were interviewed using the Structured
      Clinical Interview for DSM-IV Axis I Disorders. Needs for care were assessed
      using the community version of the Medical Research Council Needs for Care
      Assessment Schedule. RESULTS: Three hundred and thirty-six people were
      interviewed. The overall prevalence of need was 27.3%. More than half of the
      consulters (59.6%) had unmet needs and a further 6.2% had partially met needs.
      Needs were met in 28.1% and unmeetable in 6.2%. The prevalence of unmet need in
      those with anxiety disorders was 13.9% and depressive disorders 9.5%.
      CONCLUSIONS: The unmet need for mental health treatment in primary care attenders
      is high.

PMID- 15458993
TI  - Post-traumatic stress after terrorist attack: psychological reactions following
      the US embassy bombing in Nairobi: Naturalistic study.
AB  - BACKGROUND: Most studies of post-traumatic stress disorder following terrorist
      attacks are of small samples in industrialised nations and take place months or
      years after the incident. AIMS: To describe reactions following the US embassy
      bombing in Nairobi and the characteristic features of and risk factors for post
      traumatic stress symptoms in a large, non-Western sample soon after the attack.
      METHOD: A self-report questionnaire which assessed potential risk factors and
      identified symptoms matching DSM-IV criteria for post-traumatic stress disorder
      was answered by 2883 Kenyans, 1-3 months after the bombing. RESULTS: Symptoms
      approximating to the criteria for post-traumatic stress disorder occurred in 35%.
      Factors associated with post-traumatic stress included female gender, unmarried
      status, lack of college education, seeing the blast, injury, not recovering from
      injury, not confiding in a friend, bereavement and financial difficulty since the
      blast. Many other factors were not significant. CONCLUSIONS: Specific factors
      often cited to predict marked short-term post-traumatic stress were confirmed in
      this large, non-Western sample.

PMID- 15458994
TI  - Patterns of hospital admission for adult psychiatric illness in England: analysis
      of Hospital Episode Statistics data.
AB  - BACKGROUND: The assessment and reporting of national patterns of psychiatric
      hospital admissions is important for strategic service development and planning.
      AIMS: To investigate patterns of psychiatric hospital admissions of patients aged
      16-64 years in England. METHOD: We used the Department of Health's national
      Hospital Episode Statistics data on admissions to National Health Service
      hospitals in England between April 1999 and March 2000, to investigate patterns
      by region, gender, age and diagnosis. RESULTS: The annual admission rate for
      England was 3.2 per 1000 population. There were marked regional variations and
      rates were higher in males than in females. Depression and anxiety together were
      the most common (29.6%) reason for admission. Length of stay exceeded 90 days in
      9.2% of admissions and 1 year in 0.9% (highest in London and for psychoses).
      CONCLUSIONS: Depression and anxiety together were the most frequent diagnoses
      leading to hospitalisation. There has been a reversal of the previously reported
      predominance of female admissions. Regional variations in activity and the
      significant numbers of patients remaining for long periods in'acute' inpatient
      care have important policy implications.

PMID- 15458995
TI  - Effect of web-based depression literacy and cognitive-behavioural therapy
      interventions on stigmatising attitudes to depression: randomised controlled
      trial.
AB  - BACKGROUND: Little is known about the efficacy of educational interventions for
      reducing the stigma associated with depression. AIMS: To investigate the effects
      on stigma of two internet depression sites. METHOD: A sample of 525 individuals
      with elevated scores on a depression assessment scale were randomly allocated to
      a depression information website (BluePages), a cognitive-behavioural skills
      training website (MoodGYM) or an attention control condition. Personal stigma
      (personal stigmatising attitudes to depression) and perceived stigma (perception
      of what most other people believe) were assessed before and after the
      intervention. RESULTS: Relative to the control, the internet sites significantly
      reduced personal stigma, although the effects were small. BluePages had no effect
      on perceived stigma and MoodGYM was associated with an increase in perceived
      stigma relative to the control. Changes in stigma were not mediated by changes in
      depression, depression literacy or cognitive-behavioural therapy literacy.
      CONCLUSIONS: The internet warrants further investigation as a means of delivering
      stigma reduction programmes for depression.

PMID- 15458996
TI  - Affective problems in adults with mild learning disability: the roles of social
      disadvantage and ill health.
AB  - Mild learning disability is associated with an increased risk of affective
      disorder. This study examines the extent to which adult socio-economic
      disadvantage and ill health contribute to this risk. Samples were drawn from the
      1958 National Child Development Study. Relative to a comparison group, mild
      learning disability at age 11 was associated with elevated rates of depressive
      symptoms throughout adult life, and carried a six-fold risk of chronic depressed
      mood. The group difference in depressed mood at age 43 years was in large part
      mediated by variations in adult socio-economic disadvantage and ill health.

PMID- 15458997
TI  - Cannabis and psychosis.

PMID- 15458998
TI  - Child sexual abuse and substance use disorders: role of psychiatric comorbidity.

PMID- 15458999
TI  - Insulin-like growth factors, insulin resistance and schizophrenia.

PMID- 15459000
TI  - Pharmaceutical influence and psychiatrists: an introspection.

PMID- 15459001
TI  - Defining delusion.

PMID- 15459002
TI  - Twenty ways to scratch your bum?

PMID- 15459003
TI  - Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor
      antagonists on mortality and renal outcomes in diabetic nephropathy: systematic
      review.
AB  - OBJECTIVE: To evaluate the effects of angiotensin converting enzyme (ACE)
      inhibitors and angiotensin II receptor antagonists (AIIRAs) on renal outcomes and
      all cause mortality in patients with diabetic nephropathy. DATA SOURCES: Medline,
      Embase, the Cochrane controlled trials register, conference proceedings, and
      contact with investigators. STUDY SELECTION: Trials comparing ACE inhibitors or
      AIIRAs with placebo or with each other in patients with diabetic nephropathy.
      DATA EXTRACTION: Mortality, renal outcomes (end stage renal disease, doubling of
      serum creatinine concentration, prevention of progression of microalbuminuria to
      macroalbuminuria, remission of microalbuminuria), and quality of trials. DATA
      SYNTHESIS: 36 of 43 identified trials compared ACE inhibitors with placebo (4008
      patients), four compared AIIRAs with placebo (3331 patients), and three compared
      ACE inhibitors with AIIRAs (206 patients). We obtained unpublished data for 11
      trials. ACE inhibitors significantly reduced all cause mortality (relative risk
      0.79, 95% confidence interval 0.63 to 0.99) compared with placebo but AIIRAs did
      not (0.99, 0.85 to 1.17), although baseline mortality was similar in the trials.
      Both agents had similar effects on renal outcomes. Reliable estimates of the
      unconfounded relative effects of ACE inhibitors compared with AIIRAs could not be
      obtained owing to small sample sizes. CONCLUSION: Although the survival benefits
      of ACE inhibitors for patients with diabetic nephropathy are known, the relative
      effects of ACE inhibitors and AIIRAs on survival are unknown owing to the lack of
      adequate head to head trials.

PMID- 15459004
TI  - Prevention of lethal acute GVHD with an agonistic CD28 antibody and rapamycin.
AB  - Successful hematopoietic cell transplantation (HCT) from an allogeneic donor
      ideally should produce tolerance to recipient alloantigens while preserving anti
      infectious and antitumor immunity. Rapamycin together with costimulation blockade
      can induce tolerance in organ allograft models by inhibiting G(1) --> S-phase
      progression and promoting T-cell apoptosis. In contrast to blocking costimulation
      through CD28, administration of agonistic CD28-specific antibody 37.51 partially
      prevents lethal graft-versus-host disease (GVHD) by selective depletion of
      alloreactive T cells in mice. We hypothesized that combining rapamycin with
      agonistic CD28 treatment would improve GVHD control by tolerizing a small subset
      of alloreactive T cells that might escape effects of the CD28-specific antibody.
      A short course of rapamycin plus agonistic CD28 treatment showed synergism at
      suboptimal doses, was highly effective in preventing lethal GVHD, and was
      superior to rapamycin plus CD28 blockade in a major histocompatibility complex
      class I- and II-mismatched HCT model. The combination treatment reduced the
      number of proliferating, alloreactive cells in the recipient, promoted donor B-
      and T-cell reconstitution, and reduced inflammatory cytokine levels.
      Administration of rapamycin plus agonistic CD28 antibodies offers a promising new
      therapeutic approach to facilitate tolerance after HCT.

PMID- 15459005
TI  - Cross-recognition of human alloantigen by cytomegalovirus glycoprotein-specific
      CD4+ cytotoxic T lymphocytes: implications for graft-versus-host disease.
AB  - Presence of the HLA-DR7 allele in patients who receive transplants has been
      proposed as a risk factor for human cytomegalovirus (HCMV)-associated
      complications; however, the precise mechanism of this increased risk remains
      unresolved. Here we show that HLA-DR7-restricted HCMV-specific CD4(+) cytotoxic T
      lymphocytes (CTLs) can display an unusual dual specificity toward a glycoprotein
      B (gB) epitope and the alloantigen HLA-DR4. However, no HLA-DR4-specific
      alloreactivity was observed when the gB-specific CTLs were generated from virus
      carriers expressing both HLA-DR7 and DR4 alleles. This most likely demonstrates
      the clonal inactivation of potentially self-reactive T cells in humans. Fine
      specificity analysis showed that gB-specific CTLs from HLA-DR7(+)/DR4(-)
      individuals displayed a distinct pattern of recognition when compared with CTLs
      from HLA-DR7(+)/DR4(+) individuals, presumably evading an area of the epitope
      that mimics a structure presented on HLA-DR4. These data illustrate a possible
      mechanism for the clinical association between HCMV and graft-versus-host
      disease.

PMID- 15459006
TI  - Regulator of G-protein signaling-5 induction in pericytes coincides with active
      vessel remodeling during neovascularization.
AB  - We identified regulator of G-protein signaling-5 (RGS-5) as an angiogenic
      pericyte marker at sites of physiologic and pathologic angiogenesis. In a mouse
      model of pancreatic islet cell carcinogenesis, RGS-5 is specifically induced in
      the vasculature of premalignant lesions during the "angiogenic switch" and
      further elevated in tumor vessels. Similarly, RGS-5 is overexpressed in highly
      angiogenic astrocytomas but not in hypoxia-inducible factor-1alpha (HIF-1alpha)
      deficient tumors, which grow along preexisting brain capillaries without inducing
      neovessels. Elevated levels of RGS-5 in pericytes are also observed during wound
      healing and ovulation indicating a strong correlation between RGS-5 expression
      and active vessel remodeling beyond tumor angiogenesis. Moreover, antitumor
      therapy, which reverses tumor vasculature to an almost normal morphology, results
      in down-regulation of RGS-5 transcription. Taken together, these data demonstrate
      for the first time a factor that is specific for "activated" pericytes. This
      further supports the notion that pericytes, like endothelial cells, undergo
      molecular changes during neovascularization that makes them a novel target for
      antiangiogenic therapy.

PMID- 15459007
TI  - Comparative outcome of nonmyeloablative and myeloablative allogeneic
      hematopoietic cell transplantation for patients older than 50 years of age.
AB  - Nonmyeloablative stem cell transplantation (NST) is increasingly used in older
      patients. The impact of the shift from myeloablative transplantation to NST on
      relapse, transplant complications, and outcome has yet to be fully examined. We
      performed a retrospective analysis of 152 patients older than 50 years undergoing
      NST or myeloablative transplantation. Seventy-one patients received
      nonmyeloablative conditioning, fludarabine (30 mg/m(2)/d x 4) and intravenous
      busulfan (0.8 mg/kg/d x 4); 81 patients received myeloablative conditioning,
      primarily cyclophosphamide and total body irradiation. NST patients were more
      likely to have unrelated donors (58% versus 36%; P = .009), a prior transplant
      (25% versus 4%; P = < .0001), and active disease at transplantation (85% versus
      59%; P = < .001). Despite the adverse characteristics, overall survival was
      improved in the NST group at 1 year (51% versus 39%) and 2 years (39% versus 29%;
      P = .056). There was no difference in progression-free survival (2 years, 27%
      versus 25%; P = .24). The incidence of grade 2 to 4 graft-versus-host disease was
      similar (28% versus 27%). The nonrelapse mortality rate was lower for NST
      patients (32% versus 50%; P = .01), but the relapse rate was higher (46% versus
      30%; P = .052). Our experience suggests that, in patients over age 50, NST with
      fludarabine and low-dose busulfan leads to an overall outcome at least as good as
      that following myeloablative therapy.

PMID- 15459008
TI  - Von Willebrand factor accelerates platelet adhesion and thrombus formation on a
      collagen surface in platelet-reduced blood under flow conditions.
AB  - Plasma von Willebrand factor (VWF) has been identified as an indispensable factor
      for platelet adhesion and thrombus formation on a collagen surface under flow
      conditions. VWF binds to collagen and then tethers platelets to the collagen
      surface through interaction with platelet glycoprotein Ib and also contributes to
      the thrombus formation on the collagen surface. In the present study, we
      demonstrated that the addition of VWF/factor VIII complex or purified VWF (> 2
      ristocetin cofactor activity units/mL) increased platelet adhesion to the
      collagen surface in platelet-reduced blood ( approximately 5 x 10(4)
      platelets/microL) to the normal level. VWF had no stimulatory effect when it was
      allowed to bind to the collagen surface before blood flow was initiated. Addition
      of an excess of FITC (fluorescein-5-isothiocyanate)-labeled VWF to platelet
      reduced blood under these flow conditions demonstrated that the VWF was mainly
      incorporated into the platelet aggregates. These results indicated that the
      supplemented VWF stimulates the platelet adhesion onto the collagen surface by
      enhancing platelet aggregation in the platelet-reduced condition. This also
      suggests a possibility that supplementation of VWF to individuals with
      thrombocytopenia might be effective for increasing their hemostatic potential.

PMID- 15459009
TI  - Identification of a human mutation of DMT1 in a patient with microcytic anemia
      and iron overload.
AB  - Divalent metal transporter 1 (DMT1) is a transmembrane protein crucial for
      duodenal iron absorption and erythroid iron transport. DMT1 function has been
      elucidated largely in studies of the mk mouse and the Belgrade rat, which have an
      identical single nucleotide mutation of this gene that affects protein
      processing, stability, and function. These animals exhibit hypochromic microcytic
      anemia due to impaired intestinal iron absorption, and defective iron utilization
      in red cell precursors. We report here the first human mutation of DMT1
      identified in a female with severe hypochromic microcytic anemia and iron
      overload. This homozygous mutation in the ultimate nucleotide of exon 12 codes
      for a conservative E399D amino acid substitution; however, its pre-dominant
      effect is preferential skipping of exon 12 during processing of pre-messenger RNA
      (mRNA). The lack of full-length mRNA would predict deficient iron absorption in
      the intestine and deficient iron utilization in erythroid precursors; however,
      unlike the animal models of DMT1 mutation, the patient is iron overloaded. This
      does not appear to be due to up-regulation of total DMT1 mRNA. DMT1 protein is
      easily detectable by immunoblotting in the patient's duodenum, but it is unclear
      whether the protein is properly processed or targeted.

PMID- 15459010
TI  - Heterophilic interactions of platelet factor 4 and RANTES promote monocyte arrest
      on endothelium.
AB  - The chemokines platelet factor 4 (PF4) and RANTES (regulated on activation normal
      T cell expressed and secreted) are secreted by activated platelets and influence
      multiple cell types and biologic processes. For instance, PF4 inhibits progenitor
      cell proliferation and angiogenesis, while platelet-derived RANTES is involved in
      vascular recruitment of monocytes. However, little is known about functional
      interactions of PF4 and RANTES. Here we show that the presence of PF4 enhanced
      the arrest of RANTES-stimulated monocytes and monocytic cells on activated
      endothelial cells under flow conditions, while binding of PF4 to the monocyte
      surface was increased by RANTES. Both RANTES-triggered arrest and PF4 binding
      involved monocytic chondroitin sulfate. Ligand blots and surface plasmon
      resonance revealed a robust heterophilic interaction of PF4 with RANTES but not
      with RANTES variants defective in higher order oligomerization. The tetrameric
      mutant E26A bound to the monocyte surface without increasing PF4 binding, and
      monocyte arrest induced by E26A-RANTES was not enhanced by PF4. Stimulation of
      monocytes with supernatants of activated platelets triggered arrest involving
      RANTES and PF4, as shown by inhibition studies. Our results suggest that
      heterophilic interactions with PF4 require structural motifs important in RANTES
      oligomerization and amplify RANTES-triggered effects on monocyte adhesion. This
      may have implications for the modulation of inflammatory recruitment by platelet
      derived chemokines.

PMID- 15459011
TI  - A cell-based screen for resistance of Bcr-Abl-positive leukemia identifies the
      mutation pattern for PD166326, an alternative Abl kinase inhibitor.
AB  - In Philadelphia-positive (Ph(+)) leukemia, point mutations within the Bcr-Abl
      kinase domain emerged as a major mechanism of resistance to imatinib mesylate. We
      established a cell-based screening strategy for detection of clinically relevant
      point mutations using Bcr-Abl-transformed Ba/F3 cells. We identified 32 different
      single-point mutations within the kinase domain of Bcr-Abl. The pattern and
      frequency of mutations in this cell culture-based screen resembled the pattern
      and frequency observed in resistant patients. We then applied this screen to an
      alternative Abl kinase inhibitor. Using PD166326, the frequency of resistant
      colonies emerging at 5 to 10 times the median growth inhibition (IC50) of
      PD166326 was significantly lower than with imatinib. In addition, PD166326
      produced a distinct pattern of Bcr-Abl mutations. The majority of mutations that
      came up with both imatinib and PD166326 could effectively be suppressed by
      increasing the dose of PD166326 to 50 to 500 nM. In contrast, only a few
      mutations could be suppressed by increasing the imatinib dose to 5 to 10 microM.
      However, 3 mutations affecting F317 displayed complete resistance to PD166326,
      but could be effectively inhibited by standard concentrations of imatinib. Thus,
      this robust and simple screening system provides a rational basis for
      combinatorial and sequential treatment strategies in targeted cancer therapy.

PMID- 15459012
TI  - A phase 1 study of SU11248 in the treatment of patients with refractory or
      resistant acute myeloid leukemia (AML) or not amenable to conventional therapy
      for the disease.
AB  - Fifteen patients with refractory AML were treated in a phase 1 study with
      SU11248, an oral kinase inhibitor of fms-like tyrosine kinase 3 (Flt3), Kit,
      vascular endothelial growth factor (VEGF), and platelet-derived growth factor
      (PDGF) receptors. Separate cohorts of patients received SU11248 for 4-week cycles
      followed by either a 2- or a 1-week rest period. At the starting dose level of 50
      mg (n = 13), no dose-limiting toxicities were observed. The most frequent grade 2
      toxicities were edema, fatigue, and oral ulcerations. Two fatal bleedings
      possibly related to the disease, one from a concomitant lung cancer and one
      cerebral bleeding, were observed. At the 75 mg dose level (n = 2), one case each
      of grade 4 fatigue, hypertension, and cardiac failure was observed, and this dose
      level was abandoned. All patients with FLT3 mutations (n = 4) had morphologic or
      partial responses compared with 2 of 10 evaluable patients with wild-type FLT3.
      Responses, although longer in patients with mutated FLT3, were of short duration.
      Reductions of cellularity and numbers of Ki-67(+), phospho-Kit(+), phospho-kinase
      domain-containing receptor-positive (phospho-KDR(+)), phospho-signal transducer
      and activator of transcription 5-positive (phospho-STAT5(+)), and phospho-Akt(+)
      cells were detected in bone marrow histology analysis. In summary, monotherapy
      with SU11248 induced partial remissions of short duration in acute myeloid
      leukemia (AML) patients. Further evaluation of this compound, for example in
      combination with chemotherapy, is warranted.

PMID- 15459013
TI  - Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor
      kappaB activation: common genetic etiology with Blau syndrome.
AB  - Early-onset sarcoidosis (EOS) and inheritable Blau syndrome (BS) share
      characteristic clinical features of juvenile-onset systemic granulomatosis
      syndrome that mainly affects skin, joints, and eyes. However, no direct evidence
      has been shown for the possible common origin of these 2 diseases. Recent
      discovery of CARD15 mutations in BS families encouraged us to investigate similar
      CARD15 mutations in EOS patients. Among 10 EOS cases retrospectively collected in
      Japan, heterozygous missense mutations were found in 9 cases; 4 showed a 1000C>T
      (R334W in amino acid change) that has been reported in BS, 4 showed novel 1487A>T
      (H496L), 1538T>C (M513T), 1813A>C (T605P), and 2010C>A (N670K), and 1 case showed
      double 1146C>G (D382E)/1834G>A (A612T) mutations on different alleles. All 6 of
      these variants of CARD15 showed increased basal nuclear factor (NF)-kappaB
      activity. These findings indicate that the majority of EOS and BS cases share the
      common genetic etiology of CARD15 mutations that cause constitutive NF-kappaB
      activation.

PMID- 15459014
TI  - The magnitude and breadth of hepatitis C virus-specific CD8+ T cells depend on
      absolute CD4+ T-cell count in individuals coinfected with HIV-1.
AB  - CD8(+) T-cell responses are an essential antiviral host defense in persistent
      viral infections, and their sustained effectiveness is thought to be critically
      dependent on CD4(+) T-helper cells. To determine the relationship between HIV-1
      induced CD4(+) T-cell depletion and hepatitis C virus (HCV)-specific CD8(+) T
      cell responses during viral persistence, we studied 103 persons positive for HCV,
      74 coinfected with HIV-1. CD8(+) T-cell responses to the entire HCV polyprotein
      were determined by using an interferon-gamma enzyme-linked immunospot (ELISpot)
      assay. Although HIV-1 infection by itself was not associated with a diminished
      HCV-specific response, HIV-1-associated CD4(+) depletion was associated with
      significantly lower HCV-specific CD8(+) T cells (R = 0.48, P < .0001). In
      contrast, declining CD4(+) counts over the same range were not associated with
      diminished Epstein-Barr virus (EBV)- (R = 0.19, P = .31) or HIV-1-specific (R = 
      0.13, P = .60) CD8(+) T-cell responses in persons infected with all viruses.
      These data indicate that frequencies of circulating HCV-specific CD8(+) T-cell
      responses are sensitive to absolute CD4(+) T-cell counts and provide a possible
      explanation for the accelerated HCV disease course in persons coinfected with HIV
      1 and HCV.

PMID- 15459015
TI  - Early TCR-beta and TCR-gamma PCR detection of T-cell clonality indicates minimal
      tumor disease in lymph nodes of cutaneous T-cell lymphoma: diagnostic and
      prognostic implications.
AB  - The lymph nodes are generally the first extracutaneous manifestation in patients
      with cutaneous T-cell lymphoma (CTCL); however, their early involvement is
      difficult to assess. The aim of our study was to define the diagnostic and
      prognostic value of T-cell clonality analysis for a more precise assessment of
      lymph node involvement in CTCL. T-cell clonality was determined by 2 independent
      polymerase chain reaction (PCR) assays, namely a recently developed T-cell
      receptor-beta (TCR-beta) PCR technique as well as an established TCR-gamma PCR. T
      cell clonality was found in 22 of 22 lymph nodes with histologically detectable
      CTCL involvement as well as in 7 of 14 histologically noninvolved dermatopathic
      lymph nodes. The clonal T-cell populations in the lymph nodes were in all cases
      identical to those detected in the corresponding skin lesions, identifying them
      as the tumor cell population. T-cell clonality was not found in any of the 12
      dermatopathic lymph nodes from 12 patients with inflammatory skin diseases.
      Clonal T-cell detection in 7 of 14 dermatopathic lymph nodes of patients with
      CTCL was associated with limited survival (74 months; confidence interval [CI],
      66-82 months) as in patients with histologically confirmed lymph node involvement
      (41 months; CI, 35-47 months), whereas all patients without T-cell clonality in
      the lymph nodes (7 patients) were alive at the last follow-up. Thus, T-cell
      clonality analysis is an important adjunct in differentiating benign
      dermatopathic lymphadenitis from early CTCL involvement.

PMID- 15459016
TI  - PML mediates IFN-alpha-induced apoptosis in myeloma by regulating TRAIL
      induction.
AB  - Interferon (IFN) induces expression of proapoptotic genes and has been used in
      the clinical treatment of multiple myeloma. The promyelocytic leukemia (PML) gene
      is an IFN-induced target that encodes a tumor suppressor protein. PML protein is
      typically localized within discrete speckled nuclear structures termed PML
      nuclear bodies (NBs). Multiple myeloma cells demonstrate differential responses
      to IFN treatment, the mechanism of which is largely unknown. Herein, we show that
      growth inhibition effects of IFN-alpha in myeloma cells correlate with PML NBs
      and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)
      induction, whereas known IFN targets including signal transducer and activator of
      transcription-1 (STAT1), STAT3, p38, and Daxx cannot account for these
      differential responses. RNAi silencing of PML blocks IFN-alpha-induced apoptosis
      in myeloma cells and correspondingly down-regulates TRAIL expression. Similarly,
      stable expression of a dominant negative TRAIL receptor DR5 partially blocks IFN
      induced cell death. These results demonstrate that PML and TRAIL play important
      roles in IFN-induced apoptosis and identify TRAIL as a novel downstream
      transcriptional target of PML. Identification of PML and PML NBs as effectors of
      IFN responses provides insights into mechanisms by which tumor cells exhibit
      resistance to this class of agents and may prove useful in assessing treatment
      regimens.

PMID- 15459017
TI  - Involvement of connective tissue-type mast cells in Th1 immune responses via
      Stat4 expression.
AB  - Mast cells are the sentinels of immune systems and, like other immuno-competent
      cells, they are produced by hematopoietic stem cells. We analyzed the expression
      of signal transducer and activator of transcription 4 (Stat4), and investigated
      its role in mast cells. Murine mast cells are usually divided into 2 distinct
      populations by their distribution and contents of their granules: mucosal mast
      cells (MMCs) and connective tissue-type mast cells (CTMCs). Stat4 protein was
      detected in CTMCs but not in MMCs. The absence of Stat4 expression in cultured
      mast cells was due to the presence of Stat6. In T-helper (Th) cells, Stat4 plays
      an important role in Th1 shift by inducing a set of genes, such as interferon
      gamma (IFN-gamma) and interleukin-18 receptor alpha subunit (IL-18Ralpha). As in
      Th1 shift, we found that Stat4 trans-activated these genes in the Stat4
      expressing cultured mast cells, namely, microphthalmia transcription factor
      (MITF)-deficient cultured MMCs, Stat6-deficient cultured MMCs, and cultured
      CTMCs. Stat4 also enhanced expression of nitric oxide synthase 2 (NOS2) in CTMCs,
      which brought about increased levels of NO-dependent cytotoxic activity. These
      data indicate that expression of Stat4 in CTMCs plays an important role on Th1
      immune responses.

PMID- 15459018
TI  - TCDD activates Mdm2 and attenuates the p53 response to DNA damaging agents.
AB  - In this study we investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) on the p53 response to DNA damaging agents. Pre-treatment of rats with
      TCDD attenuated the p53 liver response to diethylnitrosamine (DEN) and reduced
      levels of p53 and Ser15 phosphorylated p53. In addition, there were more slowly
      migrating p53 species, forming a ladder, which suggests an increased ubiquination
      of p53 in TCDD-pre-treated rats. Terminal deoxynucleotidyl transferase-mediated X
      dUTP nick-end labelling analysis indicated decreased apoptosis rates in the
      livers of these rats. Studies on aryl hydrocarbon receptor (AhR) knockout mice
      and their wild-type littermates confirmed this effect in AhR +/+ but not in AhR 
      /- mice, indicating that this effect may be AhR-mediated. Quantitative RT-PCR
      analysis revealed no increased mRNA levels in TCDD-treated rats, but
      immunohistological studies indicated that TCDD modulated Mdm2 protein levels, and
      in particular, increased nuclear levels in rat hepatocytes in situ. In vitro
      studies employing HepG2 cells confirmed the in vivo data. Thus, TCDD increased
      basal levels of Mdm2 protein, but not mRNA, and attenuated the p53 response to a
      variety of genotoxic and cytotoxic agents. The increase in Mdm2 protein levels
      was accompanied by rapid and highly sensitive phosphorylation of Mdm2 at Ser166,
      which has been associated to active Mdm2. In summary, TCDD is a potent inhibitor
      of p53 that may influence the liver's ability to handle genotoxic agents in a
      safe way, and may play a role in TCDD-induced carcinogenesis.

PMID- 15459019
TI  - Selenium prevents tumor development in a rat model for chemical carcinogenesis.
AB  - Previous studies in animals and humans have shown that selenium compounds can
      prevent cancer development. In this work we studied the tumor preventive effect
      of selenium supplementation, administrated as selenite, in the initiation,
      promotion and progression phases in a synchronized rat model for chemically
      induced hepatocarcinogenesis, the resistant hepatocyte model. Selenite in supra
      nutritional but subtoxic doses (1 and 5 p.p.m.) was administrated to the animals
      through the drinking water. Such supplementation during the initiation phase did
      not have a tumor preventive effect. However, selenite treatment during the
      promotion phase decreased the volume fraction of pre-neoplastic liver nodules
      from 38% in control animals to 25 (1 p.p.m.) and 14% (5 p.p.m.) in the selenite
      supplemented groups. In addition the cell proliferation within the nodules
      decreased from 42% in the control to 22 (1 p.p.m.) and 17% (5 p.p.m.).
      Immunohistochemical staining for the selenoenzyme thioredoxin reductase 1
      revealed an increased expression of the enzyme in liver nodules compared with the
      surrounding tissue. The activity was reduced to 50% in liver homogenates from
      selenium-treated animals but the activity of the selenoenzyme glutathione
      peroxidase was essentially unaltered. Selenite treatment (5 p.p.m.) during the
      progression phase resulted in a significantly lower volume fraction of liver
      tumors (14 compared with 26%) along with a decrease in cell proliferation within
      the tumors (34 compared with 63%). Taken together our data indicate that the
      carcinogenetic process may be prevented by selenium supplementation both during
      the promotion and the progression phase.

PMID- 15459020
TI  - Polymorphisms in glutathione S-transferases and non-melanoma skin cancer risk in
      Australian renal transplant recipients.
AB  - Caucasian renal transplant recipients from Queensland, Australia have the highest
      non-melanoma skin cancer (NMSC) risk worldwide. Although ultraviolet light (UVR)
      exposure is critical, genetic factors also appear important. We and others have
      shown that polymorphism in the glutathione S-transferases (GST) is associated
      with NMSC in UK recipients. However, the effect of high UVR exposure and
      differences in immunosuppressive regimen on these associations is unknown. In
      this study, we examined allelism in GSTM1, GSTM3, GSTT1 and GSTP1 in 361
      Queensland renal transplant recipients. Data on squamous (SCC) and basal cell
      carcinoma (BCC), UVR/tobacco exposure and genotype were obtained. Associations
      with both NMSC risk and numbers were examined using logistic and negative
      binomial regression, respectively. In the total group, GSTM1 AB [P = 0.049, rate
      ratio (RR) = 0.23] and GSTM3 AA (P = 0.015, RR = 0.50) were associated with fewer
      SCC. Recipients were then stratified by prednisolone dose (< or =7 versus >7
      mg/day). In the low-dose group, GSTT1 null (P = 0.006, RR = 0.20) and GSTP1
      Val/Val (P = 0.021, RR = 0.20) were associated with SCC numbers. In contrast, in
      the high-dose group, GSTM1 AB (P = 0.009, RR = 0.05), GSTM3 AB (P = 0.042, RR =
      2.29) and BB (P = 0.014, RR = 5.31) and GSTP1 Val/Val (P = 0.036, RR = 2.98) were
      associated with SCC numbers. GSTM1 AB (P = 0.016) and GSTP1 Val/Val (P = 0.046)
      were also associated with fewer BCC in this group. GSTP1 associations were
      strongest in recipients with lower UVR/tobacco exposure. The data confirm our UK
      findings, suggesting that protection against UVR-induced oxidative stress is
      important in NMSC development in recipients, but that this effect depends on the
      immunosuppressant regimen.

PMID- 15459021
TI  - Colonic adenocarcinomas rapidly induced by the combined treatment with 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine and dextran sodium sulfate in male ICR mice
      possess beta-catenin gene mutations and increases immunoreactivity for beta
      catenin, cyclooxygenase-2 and inducible nitric oxide synthase.
AB  - Heterocyclic amines are known to be important environmental carcinogens in
      several organs including the colon. The aim of this study was to induce colonic
      epithelial malignancies within a short-term period and analyze the expression of
      cycooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and beta-catenin,
      and mutations of beta-catenin gene in induced tumors. Male Crj: CD-1 mice were
      given a single i.g. administration (200 mg/kg body wt) of 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) or 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx) followed by 2% dextran sodium sulfate (DSS) in the drinking
      water for a week. The expression of beta-catenin, COX-2 and iNOS was
      immunohistochemically assessed in colonic epithelial lesions and the beta-catenin
      gene mutations in colonic adenocarcinomas induced were analyzed by the single
      strand conformation polymorphism method, restriction enzyme fragment length
      polymorphism and direct sequencing. At week 16, a high incidence of colonic
      neoplasms with dysplastic lesions developed in mice that received PhIP and DSS,
      but only a few developed in those given MeIQx and DSS. Immunohistochemically, the
      adenocarcinomas induced were all positive for three proteins. All seven
      adenocarcinomas induced by PhIP and DSS have mutations. The findings suggest that
      DSS exerts powerful tumor-promoting effects on PhIP-initiated colon
      carcinogenesis in mice and this mouse model is useful for investigating
      environment-related colon carcinogenesis within a short-term period.

PMID- 15459022
TI  - Will cancer stem cells provide new therapeutic targets?
AB  - This review presents a brief synopsis of recent progress in the area of cancer
      stem cells, with emphasis on leukemia and breast cancer, and discusses potential
      limitations to accomplishing the ultimate goal of eradicating residual disease in
      cancer.

PMID- 15459023
TI  - Interactions between CYP1A1 polymorphisms and exposure to environmental tobacco
      smoke in the modulation of lymphocyte bulky DNA adducts and chromosomal
      aberrations.
AB  - CYP1A1 plays an important role in the metabolic activation of polycyclic aromatic
      hydrocarbons (PAH), carcinogenic components of air pollution. The influence of
      CYP1A1 genotype (*2A, *2B and *4) on the levels of lymphocyte bulky DNA adducts
      and the frequency of cells with aberrant chromosomes was assessed in 194 non
      smoking subjects in whom recent exposure to environmental tobacco smoke (ETS) and
      airborne particulate-associated PAH were measured during two consecutive seasons
      (winter and summer). While CYP1A1*4 had no consistent effect on either biomarker
      of genetic damage, the levels of both biomarkers responded in a parallel fashion
      to changes in exposure/CYP1A1*2A genotype combinations during both seasons.
      Specifically, the levels of both biomarkers were increased in carriers of at
      least one CYP1A1*2A allele, as compared with CYP1A1*1 homozygotes, in subjects
      with ETS exposures >0.8 h/day during the previous 4 days and mean personal
      exposure to benzo[a]pyrene <0.9 ng/m3 during the previous 24 h (all P < 0.05).
      Outside these exposure limits the differential effect in CYP1A1*2A variants was
      lost. Although the numbers of subjects with the CYP1A1*2B polymorphism was small,
      the same trend appeared to be followed in this case. These effects are
      interpreted as resulting from differential induction of CYP1A1 expression in
      CYP1A1*2A and CYP1A1*2A/*2B carriers by components of ETS-polluted air at levels
      of exposure readily suffered by large segments of the general population and
      suggest that subjects with these genotypes may have increased susceptibility to
      the genotoxic effects of ETS.

PMID- 15459024
TI  - Frontotemporal lobar degeneration with ubiquitin-only-immunoreactive neuronal
      changes: broadening the clinical picture to include progressive supranuclear
      palsy.
AB  - The frontotemporal lobar degenerations (FTLDs) are a group of disorders in which
      the clinical picture is not necessarily predictive of the underlying
      neuropathology. The FTLD with ubiquitin-only-immunoreactive neuronal changes
      (FTLD-U) subtype is pathologically characterized by ubiquitin-positive, tau and
      alpha-synuclein-negative neuronal cytoplasmic inclusions in the frontotemporal
      cortex and hippocampal dentate fascia. When similar pathological changes are
      accompanied by histological features of motor neuron disease (MND), the term FTLD
      MND is used. The latter pathological changes may be found in patients with or
      without clinical evidence of MND. We retrospectively reviewed the clinical
      details of three patients with a rapidly progressive, levodopa-unresponsive
      bradykinetic-rigid syndrome and frontal cognitive impairment. A diagnosis of
      progressive supranuclear palsy (PSP) had been considered in all three cases at
      initial presentation. Two of the cases fulfilled clinical diagnostic criteria for
      PSP, which was the final clinical diagnosis during life. Pathological analysis
      showed typical histological appearances of FTLD-MND in two cases and of FTLD-U in
      one case. Semi-quantitative analysis of pathological load seemed to correlate
      with the clinical phenotype. FTLD-U or FTLD-MND should be considered in the
      differential diagnosis of progressive frontal dementia with an akinetic rigid
      syndrome and supranuclear gaze palsy or Steele-Richardson-Olszewski disease.

PMID- 15459025
TI  - Pre-operative verbal memory fMRI predicts post-operative memory decline after
      left temporal lobe resection.
AB  - Functional MRI (fMRI) of cognitive tasks depends on technology widely available
      in the clinical sphere, but has yet to show a role in the investigation of
      patients. We report here the first demonstration of a clinically valuable role
      for cognitive fMRI. Temporal lobe epilepsy (TLE) is commonly caused by
      hippocampal sclerosis and is frequently resistant to drug treatment. Surgical
      resection of the left hippocampus in this setting can cure seizures, but may
      produce significant verbal memory decline, which is hard to predict. We report 10
      right-handed TLE patients with left hippocampal sclerosis who underwent left
      hippocampal resection. We compared currently used data for the prediction of post
      operative verbal memory decline in such patients with a novel fMRI assessment of
      verbal memory encoding. Multiple regression analyses showed that fMRI provided
      the strongest independent predictor of memory outcome after surgery. At the
      individual subject level, the fMRI data had high positive predictive value for
      memory decline.

PMID- 15459026
TI  - Who cares about academic medicine?

PMID- 15459027
TI  - Academic medicine and global health responsibilities.

PMID- 15459028
TI  - Academic medicine as a resource for global health: the case of Brazil.

PMID- 15459029
TI  - Home blood glucose monitoring in type 2 diabetes.

PMID- 15459030
TI  - Aspartame and its effects on health.

PMID- 15459031
TI  - Tobacco companies aimed to keep smokers hooked, court told.

PMID- 15459033
TI  - NICE issues guidance on sepsis.

PMID- 15459034
TI  - South Africa to regulate healers.

PMID- 15459035
TI  - US consumer body calls for review of cholesterol guidelines.

PMID- 15459048
TI  - Criminal investigation follows report on asbestos compensation fund.

PMID- 15459052
TI  - Drug intake during Ramadan.

PMID- 15459051
TI  - The hidden curriculum in undergraduate medical education: qualitative study of
      medical students' perceptions of teaching.
AB  - OBJECTIVE: To study medical students' views about the quality of the teaching
      they receive during their undergraduate training, especially in terms of the
      hidden curriculum. DESIGN: Semistructured interviews with individual students.
      SETTING: One medical school in the United Kingdom. PARTICIPANTS: 36 undergraduate
      medical students, across all stages of their training, selected by random and
      quota sampling, stratified by sex and ethnicity, with the whole medical school
      population as a sampling frame. MAIN OUTCOME MEASURES: Medical students'
      experiences and perceptions of the quality of teaching received during their
      undergraduate training. RESULTS: Students reported many examples of positive role
      models and effective, approachable teachers, with valued characteristics
      perceived according to traditional gendered stereotypes. They also described a
      hierarchical and competitive atmosphere in the medical school, in which haphazard
      instruction and teaching by humiliation occur, especially during the clinical
      training years. CONCLUSIONS: Following on from the recent reforms of the manifest
      curriculum, the hidden curriculum now needs attention to produce the necessary
      fundamental changes in the culture of undergraduate medical education.

PMID- 15459053
TI  - Obstetric issues in preterm birth.

PMID- 15459054
TI  - ICRAM (the International Campaign to Revitalise Academic Medicine): agenda
      setting.

PMID- 15459055
TI  - Academic medicine: the evidence base.

PMID- 15459056
TI  - Gender and academic medicine: impacts on the health workforce.

PMID- 15459057
TI  - Clinicians and patients' welfare: where does academic freedom fit in?

PMID- 15459058
TI  - Funding will make you free.

PMID- 15459059
TI  - Governance of academic medicine should be with public trustees.

PMID- 15459060
TI  - Reform of undergraduate medical teaching in the United Kingdom: evidence base for
      problem based learning is growing.

PMID- 15459061
TI  - Academic medicine has pitfalls for junior researchers.

PMID- 15459062
TI  - Reform of undergraduate medical teaching in the United Kingdom: students are too
      many to be assessed individually in general hospitals.

PMID- 15459063
TI  - Reform of undergraduate medical teaching in the United Kingdom: unfunded reform
      always ends in reaction.

PMID- 15459064
TI  - Reform of undergraduate medical teaching in the United Kingdom: "problem based
      learning" v "traditional" is a false debate.

PMID- 15459065
TI  - Reform of undergraduate medical teaching in the United Kingdom: evangelism
      triumphs over common sense for ophthalmology.

PMID- 15459066
TI  - Ethics: entitlement may benefit disadvantaged patients and students alike.

PMID- 15459068
TI  - Measuring participation in UK medical schools: more insight is needed.

PMID- 15459069
TI  - Measuring participation in UK medical schools: social class data are problematic
      to interpret.

PMID- 15459070
TI  - Emphasise burns prevention in developing countries.

PMID- 15459074
TI  - Platelets release CXCL4L1, a nonallelic variant of the chemokine platelet factor
      4/CXCL4 and potent inhibitor of angiogenesis.
AB  - Platelet factor-4 (PF-4)/CXCL4 was the first chemokine described to inhibit
      neovascularization. Here, the product of the nonallelic variant gene of CXCL4, PF
      4var1/PF-4alt, designated CXCL4L1, was isolated for the first time from thrombin
      stimulated human platelets and purified to homogeneity. Although secreted CXCL4
      and CXCL4L1 differ in only three amino acids, CXCL4L1 was more potent in
      inhibiting chemotaxis of human microvascular endothelial cells toward interleukin
      8 (IL-8)/CXCL8 or basic fibroblast growth factor (bFGF). In vivo, CXCL4L1 was
      also more effective than CXCL4 in inhibiting bFGF-induced angiogenesis in rat
      corneas. Thus, activated platelets release CXCL4L1, a potent regulator of
      endothelial cell biology, which affects angiogenesis and vascular diseases.

PMID- 15459075
TI  - Superoxide mediates sympathoexcitation in heart failure: roles of angiotensin II
      and NAD(P)H oxidase.
AB  - Chronic heart failure (CHF) is often associated with excitation of the
      sympathetic nervous system. This event is thought to be a negative predictor of
      survival in CHF. Sympathoexcitation and central angiotensin II (Ang II) have been
      causally linked. Recent studies have shown that NAD(P)H oxidase-derived reactive
      oxidant species (ROS) are important mediators of Ang II signaling. In the present
      study, we tested the hypothesis that central Ang II activates sympathetic outflow
      by stimulation of NAD(P)H oxidase and ROS in the CHF state. CHF was induced in
      male New Zealand White rabbits by chronic ventricular tachycardia. Using radio
      telemetry of arterial pressure and intracerebroventricular infusions, experiments
      were performed in the conscious state. Renal sympathetic nerve activity (RSNA)
      was recorded as a direct measure of sympathetic outflow. Intracerebroventricular
      Ang II significantly increased RSNA in sham (131.5+/-13.3% of control) and CHF
      (193.6+/-11.9% of control) rabbits. The increase in CHF rabbits was significantly
      greater than in sham rabbits (P<0.01). These responses were abolished by
      intracerebroventricular losartan, tempol, or apocynin. Resting RSNA was
      significantly reduced by intracerebroventricular losartan, tempol, or apocynin in
      CHF rabbits but not in sham rabbits. Intracerebroventricular administration of
      the superoxide dismutase inhibitor diethyldithio-carbamic acid increased RSNA
      significantly more in sham compared with CHF rabbits. NADPH-dependent superoxide
      anion production in the rostral ventrolateral medulla (RVLM) was increased by 2.9
      fold in CHF rabbits compared with sham rabbits. Finally, increases in the RVLM
      mRNA and protein expression of Ang II type 1 (AT1) receptor and subunits of
      NAD(P)H oxidase (p40phox, p47phox, and gp91phox) were demonstrated in CHF
      rabbits. These data demonstrate intense radical stress in autonomic areas of the
      brain in experimental CHF and provide evidence for a tight relationship between
      Ang II and ROS as contributors to sympathoexcitation in CHF.

PMID- 15459076
TI  - Attentional load and sensory competition in human vision: modulation of fMRI
      responses by load at fixation during task-irrelevant stimulation in the
      peripheral visual field.
AB  - Perceptual suppression of distractors may depend on both endogenous and exogenous
      factors, such as attentional load of the current task and sensory competition
      among simultaneous stimuli, respectively. We used functional magnetic resonance
      imaging (fMRI) to compare these two types of attentional effects and examine how
      they may interact in the human brain. We varied the attentional load of a visual
      monitoring task performed on a rapid stream at central fixation without altering
      the central stimuli themselves, while measuring the impact on fMRI responses to
      task-irrelevant peripheral checkerboards presented either unilaterally or
      bilaterally. Activations in visual cortex for irrelevant peripheral stimulation
      decreased with increasing attentional load at fixation. This relative decrease
      was present even in V1, but became larger for successive visual areas through to
      V4. Decreases in activation for contralateral peripheral checkerboards due to
      higher central load were more pronounced within retinotopic cortex corresponding
      to 'inner' peripheral locations relatively near the central targets than for more
      eccentric 'outer' locations, demonstrating a predominant suppression of nearby
      surround rather than strict 'tunnel vision' during higher task load at central
      fixation. Contralateral activations for peripheral stimulation in one hemifield
      were reduced by competition with concurrent stimulation in the other hemifield
      only in inferior parietal cortex, not in retinotopic areas of occipital visual
      cortex. In addition, central attentional load interacted with competition due to
      bilateral versus unilateral peripheral stimuli specifically in posterior parietal
      and fusiform regions. These results reveal that task-dependent attentional load,
      and interhemifield stimulus-competition, can produce distinct influences on the
      neural responses to peripheral visual stimuli within the human visual system.
      These distinct mechanisms in selective visual processing may be integrated within
      posterior parietal areas, rather than earlier occipital cortex.

PMID- 15459077
TI  - Reappraisal of DL/V4 boundaries based on connectivity patterns of dorsolateral
      visual cortex in macaques.
AB  - We placed injections of 3-5 distinguishable tracers in different dorsolateral
      locations in the visual cortex of four macaque monkeys to help define the extent
      of the dorsolateral visual complex (DL) commonly known as area V4. Injections
      well within DL/V4 region labeled neurons in V2, V3, MT, IT, and sometimes V1. In
      contrast, injections in caudal area 7a dorsal to current descriptions of DL/V4
      produced a different pattern of labeled neurons largely involving posterior
      parietal and adjoining occipital cortex, as well as cortex of the medial wall.
      Injections placed in the dorsal prelunate cortex (DP), near the expected location
      of the dorsal border of DL/V4, labeled neurons in a third pattern, including
      regions of the posterior parietal and occipital cortex, inferior temporal (IT)
      cortex, and sometimes parts of dorsal area V2, DL/V4 complex and MT. Injections
      placed near or ventral to previous estimates of the ventral border of the rostral
      divisions of DL (DLr) and near the expected rostroventral border of V4 with TEO
      labeled cells in a pattern distinctively different from either central DL/V4
      injections or those dorsal to DL/V4. Injections placed rostroventral to DL/V4
      labeled neurons over a large extent of the IT cortex, while failing to label
      neurons in V1, V2 and MT. Injections that partially involved the rostroventral
      border of DL/V4 produced a similar pattern of labeled neurons, but also labeled a
      few cells in ventral V1 and V2, as well as many in DL/V4. Dorsal and
      rostroventral injections also labeled different regions of the prefrontal cortex,
      but only DL/V4 injections that included area DP labeled neurons in the prefrontal
      cortex. The results revealed contrasting and transitional connection patterns for
      four regions of the dorsolateral visual cortex, and they provided evidence for
      the locations of dorsal and rostroventral borders of the DL/V4 complex.

PMID- 15459078
TI  - Localization of activity-dependent changes in blood volume to submillimeter-scale
      functional domains in cat visual cortex.
AB  - We have examined whether blood volume changes induced by neural activation are
      controlled precisely enough for us to visualize the submillimeter-scale
      functional structure in anesthetized and awake cat visual cortex. To activate the
      submillimeter-scale functional structures such as iso-orientation domains in the
      cortex, visual stimuli (gratings) were presented to the cats. Two methods were
      used to examine the spatial precision of blood volume changes including changes
      in total hemoglobin content and changes in plasma volume: (i) intrinsic signal
      imaging at the wavelength of hemoglobin's isosbestic point (569 nm) and (ii)
      imaging of absorption changes of an intravenously injected dye. Both measurements
      showed that the visual stimuli elicited stimulus-nonspecific and stimulus
      specific blood volume changes in the cortex. The former was not spatially
      localized, while the latter was confined to iso-orientation domains. From the
      measurement of spatial separation of the iso-orientation domains, we estimated
      the spatial resolution of stimulus-specific blood volume changes to be as high as
      0.6 mm. The changes in stimulus-nonspecific and -specific blood volume were not
      linearly correlated. These results suggest the existence of fine blood volume
      control mechanisms in the capillary bed in addition to global control mechanisms
      in arteries.

PMID- 15459079
TI  - Thalamic atrophy in Huntington's disease co-varies with cognitive performance: a
      morphometric MRI analysis.
AB  - The pattern of motor, behavioral and cognitive symptoms in Huntington's disease
      (HD) implicates dysfunction of basal-ganglia-thalamo-cortical circuits. This
      study explored if cognitive performance in HD is correlated with localized
      cerebral changes. Psychomotor functions were investigated by verbal fluency,
      Stroop color word and Digit Symbol tests in 44 HD patients and 22 controls. Three
      dimensional magnetic resonance imaging (MRI) data were analyzed with regard to
      regional gray matter changes by use of the observer-independent whole-brain-based
      approach of voxel-based morphometry (VBM). Using statistical parametric mapping,
      the MRI data of the HD patients were analyzed in an ANCOVA including the
      individual results of the neuropsychological tests. Besides striatal areas,
      symmetrical regional atrophy of the thalamus was found to co-vary significantly
      with cognitive performance (P < 0.001, corrected for multiple comparisons). In
      particular, thalamic subnuclei projecting to prefrontal areas (dorsomedial
      subnucleus) and connected to the striatum (centromedian/parafascicular and
      ventrolateral nuclear complex) displayed volume loss, in agreement with
      neuropathological studies. These results suggest that thalamic degeneration
      contributes in an important way to the impairment of executive function in early
      HD. Patients who are impaired in executive tests display structural double
      lesions of the basal-ganglia-thalamo-cortical circuitry both at the striatal and
      at the thalamic level.

PMID- 15459080
TI  - Hemispheric asymmetries for different components of global/local attention occur
      in distinct temporo-parietal loci.
AB  - Data from brain-damaged and neurologically intact populations indicate
      hemispheric asymmetries in the temporo-parietal cortex for discriminating an
      object's global form (e.g. the overall shape of a bicycle) versus its local parts
      (e.g. the spokes in a bicycle tire). However, it is not yet clear whether such
      asymmetries reflect processes that (i) bias attention toward upcoming global
      versus local stimuli and/or (ii) attend/identify global versus local stimuli
      after they are presented. To investigate these possibilities, we asked sixteen
      healthy participants to perform a cued global/local attention task while their
      brain activity was recorded using event-related functional magnetic resonance
      imaging (fMRI). The results indicated a novel double dissociation. Hemispheric
      asymmetries for deploying attention toward expected global versus local object
      features were specific to the intraparietal sulcus (iPs). However, hemispheric
      asymmetries for identifying global versus local features after they were
      presented were specific to the inferior parietal lobe/superior temporal gyrus
      (IPL/STG). This double dissociation provides the first direct evidence that
      hemispheric asymmetries associated with different components of global/local
      attention occur in distinct temporo-parietal loci. Furthermore, it parallels an
      analogous dissociation reported in a recent fMRI study of spatial orienting,
      suggesting that global/local attention and spatial attention might rely on
      similar cognitive/neural mechanisms.

PMID- 15459081
TI  - Context-dependent representation of response-outcome in monkey prefrontal
      neurons.
AB  - For behaviour to be purposeful, it is important to monitor the preceding
      behavioural context, particularly for factors regarding stimulus, response and
      outcome. The dorsolateral prefrontal cortex (DLPFC) appears to play a major role
      in such a context-dependent, flexible behavioural control system, and this area
      is likely to have a neuronal mechanism for such retrospective coding, which
      associates response-outcome with the information and/or neural systems that
      guided the response. To address this hypothesis, we recorded neuronal activity
      from the DLPFC of monkeys performing memory- and sensory-guided saccade tasks,
      each of which had two conditions with reward contingencies. We found that post
      response activity of a subset of DLPFC neurons was modulated by three factors
      relating to earlier events: the direction of the immediately preceding response,
      its outcome (reward or non-reward) and the information type (memory or sensory)
      that guided the response. Such neuronal coding should play a role in associating
      response-outcome with information and/or neural systems used to guide behaviour -
      that is, 'retrospective monitoring' of behavioural context and/or neural systems
      used for guiding behaviour - thereby contributing to context-dependent, flexible
      control of behaviours.

PMID- 15459082
TI  - Cognitive control involved in overcoming prepotent response tendencies and
      switching between tasks.
AB  - A dissociable set of regions was active for the executive processing associated
      with overcoming a prepotent response tendency and task switching. Regions
      associated with overcoming prepotency were primarily frontal and may be part of a
      system involved in top-down biasing for conflict reduction. Posterior regions
      were recruited for switching between tasks and likely play a role in
      reconfiguring stimulus-response mappings. Precuneus activity was common to both
      manipulations and may reflect increased visual attention due to more difficult
      task demands.

PMID- 15459083
TI  - Basal ganglia and cerebellar inputs to 'AIP'.
AB  - The anterior intraparietal area (AIP) is a subregion of area 7b in posterior
      parietal cortex. AIP neurons respond to the sight of objects, as well as to the
      act of grasping them. We used retrograde transneuronal transport of rabies virus
      to examine subcortical inputs to AIP in the monkey. Virus transport labeled
      substantial numbers of neurons in the substantia nigra pars reticulata (SNpr), as
      well as in the dentate nucleus of the cerebellum. The hotspots of labeled neurons
      in SNpr and in dentate after AIP injections were separate from those created by
      virus injections into several other parietal or frontal regions. These
      observations provide the first evidence that a major output nucleus of the basal
      ganglia, the SNpr, projects to a region of posterior parietal cortex. In
      addition, our findings provide further support for the concept that posterior
      parietal cortex is a target of cerebellar output.

PMID- 15459084
TI  - Nootropic agents enhance the recruitment of fast GABAA inhibition in rat
      neocortex.
AB  - It is widely believed that nootropic (cognition-enhancing) agents produce their
      therapeutic effects by augmenting excitatory synaptic transmission in cortical
      circuits, primarily through positive modulation of alpha-amino-3-hydroxy-5-methyl
      4-isoxazole-propionate receptors (AMPARs). However, GABA-mediated inhibition is
      also critical for cognition, and enhanced GABA function may be likewise
      therapeutic for cognitive disorders. Could nootropics act through such a
      mechanism as well? To address this question, we examined the effects of nootropic
      agents on excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs)
      recorded from layer V pyramidal cells in acute slices of somatosensory cortex.
      Aniracetam, a positive modulator of AMPA/kainate receptors, increased the peak
      amplitude of evoked EPSCs and the amplitude and duration of polysynaptic fast
      IPSCs, manifested as a greater total charge carried by IPSCs. As a result, the
      EPSC/IPSC ratio of total charge was decreased, representing a shift in the
      excitation-inhibition balance that favors inhibition. Aniracetam did not affect
      the magnitude of either monosynaptic IPSCs (mono-IPSCs) recorded in the presence
      of excitatory amino acid receptor antagonists, or miniature IPSCs (mIPSCs)
      recorded in the presence of tetrodotoxin. However, the duration of both mono
      IPSCs and mIPSCs was prolonged, suggesting that aniracetam also directly
      modulates GABAergic transmission. Cyclothiazide, a preferential modulator of
      AMPAR function, enhanced the magnitude and duration of polysynaptic IPSCs,
      similar to aniracetam, but did not affect mono-IPSCs. Concanavalin A, a kainate
      receptor modulator, had little effect on EPSCs or IPSCs, suggesting there was no
      contribution from kainate receptor activity. These findings indicate that AMPAR
      modulators strengthen inhibition in neocortical pyramidal cells, most likely by
      altering the kinetics of AMPARs on synaptically connected interneurons and
      possibly by modulating GABA(A) receptor responses in pyramidal cells. This
      suggests that the therapeutic actions of nootropic agents may be partly mediated
      through enhanced cortical GABAergic inhibition, and not solely through the direct
      modification of excitation, as previously thought.

PMID- 15459085
TI  - Spectral power time-courses of human sleep EEG reveal a striking discontinuity at
      approximately 18 Hz marking the division between NREM-specific and wake/REM
      specific fast frequency activity.
AB  - Spectral power time-courses over the ultradian cycle of the sleep
      electroencephalogram (EEG) provide a useful window for exploring the temporal
      correlation between cortical EEG and sub-cortical neuronal activities. Precision
      in the measurement of these time-courses is thus important, but it is hampered by
      lacunae in the definition of the frequency band limits that are in the main based
      on wake EEG conventions. A frequently seen discordance between the shape of the
      beta power time-course across the ultradian cycle and that reported for the
      sequential mean firing rate of brainstem-thalamic activating neurons invites a
      closer examination of these band limits, especially since the sleep EEG
      literature indicates in several studies an intriguing non-uniformity of time
      course comportment across the traditional beta band frequencies. We ascribe this
      tentatively to the sharp reversal of slope we have seen at approximately 18 Hz in
      our data and that of others. Here, therefore, using data for the first four
      ultradian cycles from 18 healthy subjects, we apply several criteria based on
      changes in time-course comportment in order to examine this non-uniformity as we
      move in 1 Hz bins through the frequency range 14-30 Hz. The results confirm and
      describe in detail the striking discontinuity of shape at around 18 Hz, with only
      the upper range (18-30 Hz) displaying a time-course similar to that of the firing
      rate changes measured in brainstem activating neurons and acknowledged to
      engender states of brain activation. Fast frequencies in the lower range (15-18
      Hz), on the other hand, are shown to be specific to non-rapid-eye-movement sleep.
      Splitting the beta band at approximately 18 Hz therefore permits a significant
      improvement in EEG measurement and a more precise correlation with cellular
      activity.

PMID- 15459086
TI  - Toll gates and traffic arteries: from endothelial TLR2 to atherosclerosis.

PMID- 15459087
TI  - Nuclear receptor signaling in the control of cholesterol homeostasis: have the
      orphans found a home?
AB  - Cholesterol is essential for all mammalian cells. Cellular cholesterol
      requirements are met through de novo synthesis and uptake of plasma lipoproteins,
      homeostatic responses that are transcriptionally regulated by the sterol
      regulatory element-binding proteins (SREBPs). To prevent cytotoxicity
      attributable to accumulation of excess cholesterol, liver X receptors (LXRs) and
      the farnesoid X receptor (FXR), together with other members of the nuclear
      receptor superfamily, promote the storage, transport, and catabolism of sterols
      and their metabolites. Members of this metabolic nuclear receptor family include
      receptors for oxysterols (LXRs), bile acids (CAR, FXR, and PXR), and fatty acids
      (PPARs). Through coordinated regulation of transcriptional programs, these
      nuclear receptors regulate key aspects of cellular and whole-body sterol
      homeostasis, including cholesterol absorption, lipoprotein synthesis and
      remodeling, lipoprotein uptake by peripheral tissues, reverse cholesterol
      transport, and bile acid synthesis and absorption. This review focuses on the
      nuclear receptors that are central to the lipid metabolic signaling cascades,
      communication between lipid metabolites and their receptors, and the role of
      nuclear receptors in orchestrating the complex transcriptional programs that
      govern cholesterol and bile acid metabolism.

PMID- 15459088
TI  - Mesenchymal stem cells and the artery wall.
AB  - The presence of ectopic tissue in the diseased artery wall is evidence for the
      presence of multipotential stem cells in the vasculature. Mesenchymal stem cells
      were first identified in the marrow stroma, and they differentiate along multiple
      lineages giving rise to cartilage, bone, fat, muscle, and vascular tissue in
      vitro and in vivo. Transplantation studies show that marrow-derived mesenchymal
      stem cells appear to enter the circulation and engraft other tissues, including
      the artery wall, at sites of injury. Recent evidence indicates that mesenchymal
      stem cells are also present in normal artery wall and microvessels and that they
      also may enter the circulation, contributing to the population of circulating
      progenitor cells and engrafting other tissues. Thus, the artery wall is not only
      a destination but also a source of progenitor cells that have regenerative
      potential. Although potential artifacts, such as fusion, need to be taken into
      consideration, these new developments in vascular biology open important
      therapeutic avenues. A greater understanding of how mesenchymal stem cells from
      the bone marrow or artery wall bring about vascular regeneration and repair may
      lead to novel cell-based treatments for cardiovascular disease.

PMID- 15459089
TI  - Distribution spectrum of paraoxonase activity in HDL fractions.
AB  - BACKGROUND: Paraoxonase (PON1) associated with HDL can be regarded as a cardio-
      and vasoprotective enzyme. However, because HDL is not a homogeneous fraction, it
      is important to investigate in which subgroups of HDL active PON1 is located. It
      would also be useful to determine density profiles of the HDL apolipoproteins
      (Apo) E and J. METHODS: We investigated the density range of HDL (rho = 1.063
      1.256 kg/L) in healthy individuals, using the ultracentrifugation reference
      method and a newly introduced automated fractionation method. Profiles of PON1
      activity and ApoA-I, ApoA-II, ApoE, ApoJ, and cholesterol concentrations were
      obtained by use of various density gradients. RESULTS: PON1 activity was highest
      in the more dense HDL(3) and VHDL fractions where PON1 was not dissociated from
      the particles during centrifugation. The fraction in density range 1.175-1.185
      kg/L showed not only the highest PON1 activity, but also the highest specific
      activity (activity per HDL particle). This fraction was the least-dense fraction
      containing both ApoE and ApoJ. Only the Q192R polymorphism had an effect on the
      distribution profile of PON1 activity. In contrast, L55M and the T(-107)C
      polymorphisms (determined by a novel nonradioactive method) were without effect
      on the density distribution of PON1 activity. CONCLUSION: The HDL(3) fraction,
      which is important in reverse cholesterol transport, also carries the highest
      PON1 activity.

PMID- 15459090
TI  - Measurement of folates in serum and conventionally prepared whole blood lysates:
      application of an automated 96-well plate isotope-dilution tandem mass
      spectrometry method.

PMID- 15459091
TI  - Relationship between serum lipoprotein ratios and insulin resistance in obesity.
AB  - BACKGROUND: The fasting serum lipid profile [triglycerides (TGs), total
      cholesterol (TC), and LDL- and HDL-cholesterol (LDL-C and HDL-C)] is used to
      calculate lipid ratios (TC/HDL-C, LDL-C/HDL-C, TG/HDL-C) that allow
      identification of individuals at increased risk for cardiovascular disease.
      Because these individuals are also frequently insulin resistant, this study
      analyzed the relationships between lipid ratios and insulin sensitivity. METHODS:
      In 132 obese [mean (SE) body mass index, 37.5 (0.6) kg/m(2)] outpatients without
      known diabetes mellitus, fasting serum lipid profiles and 75-g oral glucose
      tolerance tests were performed. Insulin sensitivity was assessed from surrogate
      estimates for fasting (QUICKI) and dynamic (OGIS) conditions. RESULTS: After
      exclusion of other endocrine diseases (n = 35), the remaining patients were
      classified as glucose tolerant (n = 56), glucose intolerant (n = 22), or as
      having type 2 diabetes (n = 19). QUICKI and OGIS indicated severe insulin
      resistance in all individuals with type 2 diabetes and impaired glucose tolerance
      compared with glucose-tolerant individuals: QUICKI, glucose tolerant, 0.302
      (0.002); glucose intolerant, 0.290 (0.002); type 2 diabetes, 0.281 (0.005); P
      <0.001; OGIS (mL . m(-2) . min(-1)), glucose tolerant, 343 (7), glucose
      intolerant, 293 (9); type 2 diabetes, 256 (12); P <0.001. Serum TG (P <0.005) and
      TG/HDL-C ratios (P <0.05) were increased in individuals with impaired glucose
      tolerance. TG/HDL-C ratios negatively correlated with QUICKI (r = -0.370; P <
      0.001) and OGIS (r = -0.333; P < 0.005) in nondiabetic individuals (glucose
      tolerant plus glucose intolerant), but not in patients with type 2 diabetes (not
      significant). CONCLUSIONS: This study demonstrates that the TG/HDL-C ratio
      positively correlates with insulin resistance in severely obese nondiabetic
      individuals.

PMID- 15459092
TI  - Additional data for oligonucleotide arrays of the p53 gene in DNA from formalin
      fixed, paraffin-embedded tissue.

PMID- 15459093
TI  - Photonic crystal glucose-sensing material for noninvasive monitoring of glucose
      in tear fluid.
AB  - BACKGROUND: We recently developed a photonic crystal glucose-sensing material,
      which consists of a crystalline colloidal array embedded within a polymer network
      of a polyacrylamide-poly(ethylene glycol) hydrogel with pendent phenylboronic
      acid groups. The aim of the present work was to improve this approach for
      application to noninvasive or minimally invasive monitoring of glucose. METHODS:
      We used new boronic acid derivatives such as 4-amino-3-fluorophenylboronic acid
      and 4-carboxy-3-fluorophenylboronic acid as the molecular recognition elements to
      achieve sensing at physiologic pH values. RESULTS: The improved photonic glucose
      sensing material sensed glucose in the range of the 100 mumol/L concentrations
      found in tear fluid. The detection limits were approximately 1 mumol/L in
      synthetic tear fluid. The visually evident diffraction color shifted across the
      entire visible spectral region from red to blue over the physiologically relevant
      tear-fluid glucose concentrations. This sensing material is selective for glucose
      over galactose, mannose, and fructose. CONCLUSIONS: These new glucose sensors
      have properties appropriate for use in such glucose-sensing applications as
      ocular inserts or diagnostic contact lenses for patients with diabetes mellitus.

PMID- 15459094
TI  - Selenium metabolites in urine: a critical overview of past work and current
      status.
AB  - BACKGROUND: Selenium is an essential trace element that also elicits toxic
      effects at modest intakes. Investigations of selenium metabolites in urine can
      help our understanding of the transformations taking place in the body that
      produce these beneficial and detrimental effects. There is, however, considerable
      discord in the scientific literature regarding the selenium metabolites thought
      to play important roles in these biotransformation processes. APPROACH: We
      critically assessed the published reports on selenium urinary metabolites, from
      the first report in 1969 to the present, in terms of the rigor of the data on
      which structures have been proposed. CONTENT: We present and discuss data from
      approximately 60 publications reporting a total of 16 identified selenium
      metabolites in urine of humans or rats, a good model for human selenium
      metabolism. We assessed the analytical methods used and the validity of the
      ensuing structural assignments. SUMMARY: Many of the studies of selenium
      metabolites in urine appear to have assigned incorrect structures to the
      compounds. The long-held view that trimethylselenonium ion is a major human
      urinary metabolite appears unjustified. On the other hand, recent work describing
      selenosugars as major urinary metabolites looks sound and provides a firm basis
      for future studies.

PMID- 15459095
TI  - Cerebrospinal fluid leakage: agarose gel electrophoresis detection of beta(2)
      transferrin and nephelometric quantification of beta-trace protein.

PMID- 15459096
TI  - How different is Venus from Mars? The genetics of germ-line stem cells in
      Drosophila females and males.
AB  - In the fruit fly Drosophila melanogaster, both spermatogenesis and oogenesis rely
      on germ-line stem cells (GSCs). Intensive research has revealed many of the
      molecules and pathways that underlie GSC maintenance and differentiation in males
      and females. In this review, we discuss new studies that, some differences
      notwithstanding, highlight the similarities in the structural and molecular
      strategies used by the two sexes in GSC maintenance and differentiation. These
      include the tight control that somatic support cells exert on every aspect of GSC
      function and the similar molecular mechanisms for physical attachment, cell-cell
      signaling and gap-junction communication. Some common principles underlying GSC
      biology in the fly may be applied to stem cells in other organisms.

PMID- 15459097
TI  - Drosophila contactin, a homolog of vertebrate contactin, is required for septate
      junction organization and paracellular barrier function.
AB  - Septate junctions (SJs) in epithelial and neuronal cells play an important role
      in the formation and maintenance of charge and size selective barriers. They form
      the basis for the ensheathment of nerve fibers in Drosophila and for the
      attachment of myelin loops to axonal surface in vertebrates. The cell-adhesion
      molecules NRX IV/Caspr/Paranodin (NCP1), contactin and Neurofascin-155 (NF-155)
      are all present at the vertebrate axo-glial SJs. Mutational analyses have shown
      that vertebrate NCP1 and its Drosophila homolog, Neurexin IV (NRX IV) are
      required for the formation of SJs. In this study, we report the genetic,
      molecular and biochemical characterization of the Drosophila homolog of
      vertebrate contactin, CONT. Ultrastructural and dye-exclusion analyses of Cont
      mutant embryos show that CONT is required for organization of SJs and
      paracellular barrier function. We show that CONT, Neuroglian (NRG) (Drosophila
      homolog of NF-155) and NRX IV are interdependent for their SJ localization and
      these proteins form a tripartite complex. Hence, our data provide evidence that
      the organization of SJs is dependent on the interactions between these highly
      conserved cell-adhesion molecules.

PMID- 15459098
TI  - Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis
      of the outflow tract during heart development.
AB  - Tbx2 is a member of the T-box transcription factor gene family, and is expressed
      in a variety of tissues and organs during embryogenesis. In the developing heart,
      Tbx2 is expressed in the outflow tract, inner curvature, atrioventricular canal
      and inflow tract, corresponding to a myocardial zone that is excluded from
      chamber differentiation at 9.5 days post coitus (dpc). We have used targeted
      mutagenesis in mice to investigate Tbx2 function. Mice heterozygous for a Tbx2
      null mutation appear normal but homozygous embryos reveal a crucial role for Tbx2
      during cardiac development. Morphological defects are observed in development of
      the atrioventricular canal and septation of the outflow tract. Molecular analysis
      reveals that Tbx2 is required to repress chamber differentiation in the
      atrioventricular canal at 9.5 dpc. Analysis of homozygous mutants also highlights
      a role for Tbx2 during hindlimb digit development. Despite evidence that TBX2
      negatively regulates the cell cycle control genes Cdkn2a, Cdkn2b and Cdkn1a in
      cultured cells, there is no evidence that loss of Tbx2 function during mouse
      development results in increased levels of p19(ARF), p16(INK4a), p15(INK4b) or
      p21 expression in vivo, nor is there evidence for a genetic interaction between
      Tbx2 and p53.

PMID- 15459099
TI  - Citron kinase is an essential effector of the Pbl-activated Rho signalling
      pathway in Drosophila melanogaster.
AB  - Pebble (Pbl)-activated RhoA signalling is essential for cytokinesis in Drosophila
      melanogaster. Here we report that the Drosophila citron gene encodes an essential
      effector kinase of Pbl-RhoA signalling in vivo. Drosophila citron is expressed in
      proliferating tissues but is downregulated in differentiating tissues. We find
      that Citron can bind RhoA and that localisation of Citron to the contractile ring
      is dependent on the cytokinesis-specific Pbl-RhoA signalling. Phenotypic analysis
      of mutants showed that citron is required for cytokinesis in every tissue
      examined, with mutant cells exhibiting multinucleate and hyperploid phenotypes.
      Strong genetic interactions were observed between citron and pbl alleles and
      constructs. Vertebrate studies implicate at least two Rho effector kinases,
      Citron and Rok, in cytokinesis. By contrast, we failed to find evidence for a
      role for the Drosophila ortholog of Rok in cell division. We conclude that Citron
      plays an essential, non-redundant role in the Rho signalling pathway during
      Drosophila cytokinesis.

PMID- 15459100
TI  - New roles for FoxH1 in patterning the early embryo.
AB  - FoxH1 (Fast1) was first characterized as the transcriptional partner for Smad
      proteins. Together with Smad2/4, it forms the activin response factor (ARF) that
      binds to the Mix.2 promoter in Xenopus embryos. Foxh1 is expressed maternally in
      Xenopus. Depletion of maternal Foxh1 mRNA results in abnormalities of head and
      dorsal axis formation. We show that FoxH1 is required, together with XTcf3/beta
      catenin, to activate the zygotic expression of the nodal gene, Xnr3 in a Smad2
      independent manner. In contrast, maternal FoxH1 acts as an inhibitor of Xnr5 and
      6 transcription, preventing their upregulation on the ventral side of the embryo,
      by the maternal T-box transcription factor VegT. We conclude that maternal FoxH1
      has essential, context-dependent roles in regulating the pattern of zygotic gene
      expression in the early embryo.

PMID- 15459101
TI  - Germline stem cells in the Drosophila ovary descend from pole cells in the
      anterior region of the embryonic gonad.
AB  - A fundamental yet unexplored question in stem cell biology is how the fate of
      tissue stem cells is initially determined during development. In Drosophila,
      germline stem cells (GSCs) descend from a subset of primordial germ cells (PGCs)
      at the onset of oogenesis. GSC determination may occur at the onset of oogenesis
      when a subset of PGCs is induced to become GSCs by contacting niche cells.
      Alternatively, the GSC fate could be predetermined for a subset of PGCs before
      oogenesis, due to either their interaction with specific somatic cells in the
      embryonic/larval gonads, or their inherently heterogeneous potential in becoming
      GSCs, or both. Here, we show that anterior somatic cells in the embryonic gonad
      already differ from posterior somatic cells and are likely to be the precursors
      of niche cells in the adult ovary. Furthermore, only pole cells in the anterior
      half of the embryonic gonad give rise to the PGCs that frequently acquire contact
      with nascent niche cells in the late larval ovary. Eventually, only these
      contacting PGCs become GSCs, whereas non-contacting PGCs directly differentiate
      into cystoblasts. The strong preference of these 'anterior PGCs' towards
      contacting niche cells does not require DE-cadherin-mediated adhesion and is not
      correlated with either orientation or rate of their divisions. These data suggest
      that the GSC fate is predetermined before oogenesis. The predetermination
      probably involves soma/pole-cell interaction in the anterior half of the
      embryonic gonad, followed by an active homing mechanism during PGC proliferation
      to maintain the contact between the 'anterior PGCs' and anterior somatic cells.

PMID- 15459102
TI  - Pax8 and Pax2a function synergistically in otic specification, downstream of the
      Foxi1 and Dlx3b transcription factors.
AB  - The vertebrate inner ear arises from an ectodermal thickening, the otic placode,
      that forms adjacent to the presumptive hindbrain. Previous studies have suggested
      that competent ectodermal cells respond to Fgf signals from adjacent tissues and
      express two highly related paired box transcription factors Pax2a and Pax8 in the
      developing placode. We show that compromising the functions of both Pax2a and
      Pax8 together blocks zebrafish ear development, leaving only a few residual otic
      cells. This suggests that Pax2a and Pax8 are the main effectors downstream of Fgf
      signals. Our results further provide evidence that pax8 expression and pax2a
      expression are regulated by two independent factors, Foxi1 and Dlx3b,
      respectively. Combined loss of both factors eliminates all indications of otic
      specification. We suggest that the Foxi1-Pax8 pathway provides an early
      'jumpstart' of otic specification that is maintained by the Dlx3b-Pax2a pathway.

PMID- 15459103
TI  - Wnt signals across the plasma membrane to activate the beta-catenin pathway by
      forming oligomers containing its receptors, Frizzled and LRP.
AB  - Wnt-induced signaling via beta-catenin plays crucial roles in animal development
      and tumorigenesis. Both a seven-transmembrane protein in the Frizzled family and
      a single transmembrane protein in the LRP family (LDL-receptor-related protein
      5/6 or Arrow) are essential for efficiently transducing a signal from Wnt, an
      extracellular ligand, to an intracellular pathway that stabilizes beta-catenin by
      interfering with its rate of destruction. However, the molecular mechanism by
      which these two types of membrane receptors synergize to transmit the Wnt signal
      is not known. We have used mutant and chimeric forms of Frizzled, LRP and Wnt
      proteins, small inhibitory RNAs, and assays for beta-catenin-mediated signaling
      and protein localization in Drosophila S2 cells and mammalian 293 cells to study
      transmission of a Wnt signal across the plasma membrane. Our findings are
      consistent with a mechanism by which Wnt protein binds to the extracellular
      domains of both LRP and Frizzled receptors, forming membrane-associated hetero
      oligomers that interact with both Disheveled (via the intracellular portions of
      Frizzled) and Axin (via the intracellular domain of LRP). This model takes into
      account several observations reported here: the identification of intracellular
      residues of Frizzled required for beta-catenin signaling and for recruitment of
      Dvl to the plasma membrane; evidence that Wnt3A binds to the ectodomains of LRP
      and Frizzled; and demonstrations that a requirement for Wnt ligand can be
      abrogated by chimeric receptors that allow formation of Frizzled-LRP hetero
      oligomers. In addition, the beta-catenin signaling mediated by ectopic expression
      of LRP is not dependent on Disheveled or Wnt, but can also be augmented by
      oligomerization of LRP receptors.

PMID- 15459104
TI  - Reelin is a positional signal for the lamination of dentate granule cells.
AB  - Reelin is required for the proper positioning of neurons in the cerebral cortex.
      In the reeler mutant lacking reelin, the granule cells of the dentate gyrus fail
      to form a regular, densely packed cell layer. Recent evidence suggests that this
      defect is due to the malformation of radial glial processes required for granule
      cell migration. Here, we show that recombinant reelin in the medium significantly
      increases the length of GFAP-positive radial glial fibers in slice cultures of
      reeler hippocampus, but does not rescue either radial glial fiber orientation or
      granule cell lamination. However, rescue of radial glial fiber orientation and
      granule cell lamination was achieved when reelin was present in the normotopic
      position provided by wild-type co-culture, an effect that is blocked by the CR-50
      antibody against reelin. These results indicate a dual function of reelin in the
      dentate gyrus, as a differentiation factor for radial glial cells and as a
      positional cue for radial fiber orientation and granule cell migration.

PMID- 15459105
TI  - Time-lapse and cell ablation reveal the role of cell interactions in fly glia
      migration and proliferation.
AB  - Migration and proliferation have been mostly explored in culture systems or fixed
      preparations. We present a simple genetic model, the chains of glia moving along
      fly wing nerves, to follow such dynamic processes by time-lapse in the whole
      animal. We show that glia undergo extensive cytoskeleton and mitotic apparatus
      rearrangements during division and migration. Single cell labelling identifies
      different glia: pioneers with high filopodial, exploratory, activity and, less
      active followers. In combination with time-lapse, altering this cellular
      environment by genetic means or cell ablation has allowed to us define the role
      of specific cell-cell interactions. First, neurone-glia interactions are not
      necessary for glia motility but do affect the direction of migration. Second,
      repulsive interactions between glia control the extent of movement. Finally,
      autonomous cues control proliferation.

PMID- 15459106
TI  - Transdifferentiation of the retina into pigmented cells in ocular retardation
      mice defines a new function of the homeodomain gene Chx10.
AB  - The homeodomain transcription factor Chx10 is one of the earliest markers of the
      developing retina. It is required for retinal progenitor cell proliferation as
      well as formation of bipolar cells, a type of retinal interneuron. or(J) (ocular
      retardation) mice, which are Chx10 null mutants, are microphthalmic and show
      expanded and abnormal peripheral structures, including the ciliary body. We show
      here, in a mixed genetic background, the progressive appearance of pigmented
      cells in the neural retina, concomitant with loss of expression of retinal
      markers. Fate mapping analysis using a multifunctional Chx10 BAC reporter mouse
      revealed this process to be direct transdifferentiation of retinal cells into
      pigmented cells. Microarray and in situ hybridization analyses revealed a complex
      program underlying the transdifferentiation. This program involved the expansion
      of expression of genes normally found only in the periphery into central regions
      of the eye. These genes included a transcription factor controlling pigmentation,
      Mitf, and the related factor Tfec (Tcfec -- Mouse Genome Informatics), which can
      activate a melanogenic gene expression program. Misexpression of Chx10 in the
      developing retinal pigmented epithelium (RPE) caused downregulation of Mitf,
      Tfec, and associated pigment markers, leading to a nonpigmented RPE. These data
      link Chx10 and Mitf to maintenance of the neural retina and RPE fates
      respectively. Further, they suggest a new role for Chx10 in maintenance of
      compartment boundaries in the peripheral retina.

PMID- 15459107
TI  - A phylogenetically conserved cis-regulatory module in the Msx2 promoter is
      sufficient for BMP-dependent transcription in murine and Drosophila embryos.
AB  - To understand the actions of morphogens, it is crucial to determine how they
      elicit different transcriptional responses in different cell types. Here, we
      identify a BMP-responsive enhancer of Msx2, an immediate early target of bone
      morphogenetic protein (BMP) signaling. We show that the BMP-responsive region of
      Msx2 consists of a core element, required generally for BMP-dependent expression,
      and ancillary elements that mediate signaling in diverse developmental settings.
      Analysis of the core element identified two classes of functional sites: GCCG
      sequences related to the consensus binding site of Mad/Smad-related BMP signal
      transducers; and a single TTAATT sequence, matching the consensus site for
      Antennapedia superclass homeodomain proteins. Chromatin immunoprecipitation and
      mutagenesis experiments indicate that the GCCG sites are direct targets of BMP
      restricted Smads. Intriguingly, however, these sites are not sufficient for BMP
      responsiveness in mouse embryos; the TTAATT sequence is also required. DNA
      sequence comparisons reveal this element is highly conserved in Msx2 promoters
      from mammalian orders but is not detectable in other vertebrates or non
      vertebrates. Despite this lack of conservation outside mammals, the Msx2 BMP
      responsive element serves as an accurate readout of Dpp signaling in a distantly
      related bilaterian - Drosophila. Strikingly, in Drosophila embryos, as in mice,
      both TTAATT and GCCG sequences are required for Dpp responsiveness, showing that
      a common cis-regulatory apparatus can mediate the transcriptional activation of
      BMP-regulated genes in widely divergent bilaterians.

PMID- 15459108
TI  - Developmental architecture of adult-specific lineages in the ventral CNS of
      Drosophila.
AB  - In Drosophila most thoracic neuroblasts have two neurogenic periods: an initial
      brief period during embryogenesis and a second prolonged phase during larval
      growth. This study focuses on the adult-specific neurons that are born primarily
      during the second phase of neurogenesis. The fasciculated neurites arising from
      each cluster of adult-specific neurons express the cell-adhesion protein
      Neurotactin and they make a complex scaffold of neurite bundles within the
      thoracic neuropils. Using MARCM clones, we identified the 24 lineages that make
      up the scaffold of a thoracic hemineuromere. Unlike the early-born neurons that
      are strikingly diverse in both form and function, the adult specific cells in a
      given lineage are remarkably similar and typically project to only one or two
      initial targets, which appear to be the bundled neurites from other lineages.
      Correlated changes in the contacts between the lineages in different segments
      suggest that these initial contacts have functional significance in terms of
      future synaptic partners. This paper provides an overall view of the initial
      connections that eventually lead to the complex connectivity of the bulk of the
      thoracic neurons.

PMID- 15459109
TI  - Ablation of TrkA function in the immune system causes B cell abnormalities.
AB  - The nerve growth factor (NGF) receptor TrkA is widely expressed in non-neural
      tissues suggesting pleiotropic functions outside the nervous system. Based on
      pharmacological and immuno-depletion experiments, it has been hypothesized that
      NGF plays an important role in the normal development and function of the immune
      system. However, attempts to unravel these functions by conventional gene
      targeting in mice have been hampered by the early postnatal lethality caused by
      null mutations. We have developed a novel 'reverse conditional' gene targeting
      strategy by which TrkA function is restored specifically in the nervous system.
      Mice lacking TrkA in non-neuronal tissues are viable and appear grossly normal.
      All major immune system cell populations are present in normal numbers and
      distributions. However, mutant mice have elevated serum levels of certain
      immunoglobulin classes and accumulate B1 cells with aging. These data, confirmed
      in a classical reconstitution model using embryonic fetal liver from TrkA-null
      mice, demonstrate that endogenous NGF modulates B cell development through TrkA
      in vivo. Furthermore, they demonstrate that many of the dramatic effects
      previously reported by pharmacological or immuno-depletion approaches do not
      reflect physiological developmental roles of TrkA in the immune system.

PMID- 15459110
TI  - A null mutation of Hhex results in abnormal cardiac development, defective
      vasculogenesis and elevated Vegfa levels.
AB  - The homeobox gene Hhex has recently been shown to be essential for normal liver,
      thyroid and forebrain development. Hhex(-/-) mice die by mid-gestation (E14.5)
      and the cause of their early demise remains unclear. Because Hhex is expressed in
      the developing blood islands at E7.0 in the endothelium of the developing
      vasculature and heart at E9.0-9.5, and in the ventral foregut endoderm at E8.5
      9.0, it has been postulated to play a critical role in heart and vascular
      development. We show here, for the first time, that a null mutation of Hhex
      results in striking abnormalities of cardiac and vascular development which
      include: (1) defective vasculogenesis, (2) hypoplasia of the right ventricle, (3)
      overabundant endocardial cushions accompanied by ventricular septal defects,
      outflow tract abnormalities and atrio-ventricular (AV) valve dysplasia and (4)
      aberrant development of the compact myocardium. The dramatic enlargement of the
      endocardial cushions in the absence of Hhex is due to decreased apoptosis and
      dysregulated epithelial-mesenchymal transformation (EMT). Interestingly, vascular
      endothelial growth factor A (Vegfa) levels in the hearts of Hhex(-/-) mice were
      elevated as much as three-fold between E9.5 and E11.5, and treatment of cultured
      Hhex(-/-) AV explants with truncated soluble Vegfa receptor 1, sFlt-1, an
      inhibitor of Vegf signaling, completely abolished the excessive epithelial
      mesenchymal transformation seen in the absence of Hhex. Therefore, Hhex
      expression in the ventral foregut endoderm and/or the endothelium is necessary
      for normal cardiovascular development in vivo, and one function of Hhex is to
      repress Vegfa levels during development.

PMID- 15459111
TI  - Regulation of luteinizing hormone/chorionic gonadotropin receptor messenger
      ribonucleic acid expression in the rat ovary: relationship to cholesterol
      metabolism.
AB  - Down-regulation of LH/human chorionic gonadotropin (hCG) receptor (LHR) mRNA in
      the ovary after the preovulatory LH surge or the administration of a
      pharmacological dose of LH/hCG occurs through a posttranscriptional mechanism. A
      LHR mRNA-binding protein was identified as the LHR mRNA destabilizing factor, and
      its identity was established as mevalonate kinase (Mvk). In the present study, we
      determined that, in the pseudopregnant rat ovary, LHR mRNA levels began to fall 4
      h after hCG injection, at which time Mvk protein levels were elevated, and this
      elevation was preceded by an increase in Mvk mRNA levels. When the cytosolic
      fractions of hCG-treated ovaries were subjected to RNA EMSA, an increase in LHR
      mRNA-LHR mRNA-binding protein complex formation was observed, in parallel with
      the increase of Mvk expression. We also found that hCG coordinately up-regulated
      the expression of Mvk and other sterol-responsive elements containing cholesterol
      biosynthesis enzymes, such as 3-hydroxy-3-methylglutaryl-coenzyme A synthase, 3
      hydroxy-3-methylglutaryl-coenzyme A reductase, and farnesyl pyrophosphate
      synthase. This up-regulation was transient, but the hCG-induced ovarian
      cholesterol depletion lasted for more than 24 h. Taken together, our results
      suggest that, in the ovary, LH/hCG up-regulates the expression of cholesterol
      biosynthesis enzymes and lipoprotein receptors to replenish cellular cholesterol,
      and the up-regulation of Mvk leads to a down-regulation of LHR and suppresses the
      LH/hCG signal cascade transiently. Thus Mvk, an enzyme involved in cholesterol
      biosynthesis, serves as a link between LHR mRNA expression and cellular
      cholesterol metabolism.

PMID- 15459112
TI  - Silymarin protects pancreatic beta-cells against cytokine-mediated toxicity:
      implication of c-Jun NH2-terminal kinase and janus kinase/signal transducer and
      activator of transcription pathways.
AB  - Silymarin is a polyphenolic flavonoid that has a strong antioxidant activity and
      exhibits anticarcinogenic, antiinflammatory, and cytoprotective effects. Although
      its hepatoprotective effect has been well documented, the effect of silymarin on
      pancreatic beta-cells is largely unknown. In this study, the effect of silymarin
      on IL-1beta and/or interferon (IFN)-gamma-induced beta-cell damage was
      investigated using RINm5F cells and human islets. IL-1beta and/or IFN-gamma
      induced cell death in a time-dependent manner in RINm5F cells. The time-dependent
      increase in cytokine-induced cell death appeared to correlate with the time
      dependent nitric oxide (NO) production. Silymarin dose-dependently inhibited both
      cytokine-induced NO production and cell death in RINm5F cells. Treatment of human
      islets with a combination of IL-1beta and IFN-gamma (IL-1beta+IFN-gamma), for 48
      h and 5 d, resulted in an increase of NO production and the impairment of glucose
      stimulated insulin secretion, respectively. Silymarin prevented IL-1beta+IFN
      gamma-induced NO production and beta-cell dysfunction in human islets. These
      cytoprotective effects of silymarin appeared to be mediated through the
      suppression of c-Jun NH2-terminal kinase and Janus kinase/signal transducer and
      activator of transcription pathways. Our data show a direct cytoprotective effect
      of silymarin in pancreatic beta-cells and suggest that silymarin may be
      therapeutically beneficial for type 1 diabetes.

PMID- 15459113
TI  - Changes in mouse granulosa cell gene expression during early luteinization.
AB  - Changes in gene expression during granulosa cell luteinization have been measured
      using serial analysis of gene expression (SAGE). Immature normal mice were
      treated with pregnant mare serum gonadotropin (PMSG) or PMSG followed, 48 h
      later, by human chorionic gonadotropin (hCG). Granulosa cells were collected from
      preovulatory follicles after PMSG injection or PMSG/hCG injection and SAGE
      libraries generated from the isolated mRNA. The combined libraries contained
      105,224 tags representing 40,248 unique transcripts. Overall, 715 transcripts
      showed a significant difference in abundance between the two libraries of which
      216 were significantly down-regulated by hCG and 499 were significantly up
      regulated. Among transcripts differentially regulated, there were clear and
      expected changes in genes involved in steroidogenesis as well as clusters of
      genes involved in modeling of the extracellular matrix, regulation of the
      cytoskeleton and intra and intercellular signaling. The SAGE libraries described
      here provide a base for functional investigation of the regulation of granulosa
      cell luteinization.

PMID- 15459115
TI  - Activation of peroxisome proliferator-activated receptor-gamma and retinoid X
      receptor inhibits aromatase transcription via nuclear factor-kappaB.
AB  - Our previous studies demonstrated that a peroxisome proliferator-activated
      receptor (PPAR)-gamma ligand, troglitazone (TGZ),and/or a retinoid X receptor
      (RXR) ligand, LG100268 (LG), decreased the aromatase activity in both cultured
      human ovarian granulosa cells and human granulosa-like tumor KGN cells. In the
      present study, we further found that a combined treatment of TGZ+LG decreased
      aromatase promoter II (ArPII) activity in both ovarian KGN cells and fibroblast
      NIH-3T3 cells in a PPARgamma-dependent manner. Furthermore, the inhibition of
      both aromatase activity and the transcription of ArPII by TGZ+LG was completely
      eliminated when nuclear factor-kappaB (NF-kappaB) signaling was blocked by
      specific inhibitors, suggesting NF-kappaB, which is endogenously expressed in
      both fibroblast and granulosa cells, might be a mediator of this inhibition.
      Interestingly, activation of NF-kappaB by either forced expression of the p65
      subunit or NF-kappaB-inducing kinase up-regulated ArPII activity. Positive
      regulation of aromatase by endogenous NF-kappaB was also suggested by the fact
      that NF-kappaB-specific inhibitors suppress basal activity of the aromatase gene.
      A concomitant formation of high-order complex between NF-kappaB p65 and ArPII was
      also observed by chromatin immunoprecipitation assay. Although activation of
      PPARgamma and RXR affected endogenous expression levels of neither inhibitory
      kappaBalpha nor p65, it impaired the interaction between NF-kappaB and ArPII and
      the p65 based transcription as well. Altogether, these results indicate that
      activation of a nuclear receptor system, constituted by PPARgamma and RXR, down
      regulates aromatase expression through the suppression of NF-kappaB-dependent
      aromatase activation and thus provide a new insight in the mechanism of
      regulation of the aromatase gene.

PMID- 15459114
TI  - Epidermal growth factor facilitates epinephrine inhibition of P2X7-receptor
      mediated pore formation and apoptosis: a novel signaling network.
AB  - Epidermal growth factor (EGF), epinephrine, and the P2X7 receptor system regulate
      growth of human uterine cervical epithelial cells, but little is known about how
      these systems intercommunicate in exerting their actions. The objective of this
      study was to understand the mechanisms of EGF and epinephrine regulation of
      growth of cervical cells. Treatment of cultured CaSki cells with 0.2 nM EGF
      increased cell number via a PD98059-sensitive pathway. Treatment with 2 nM
      epinephrine increased cell number, and the effect was facilitated by cotreatment
      with EGF. Whereas the effect of EGF alone involved up-regulation of [3H]
      thymidine incorporation and an increase in cell proliferation, the effect of
      epinephrine was mediated by inhibition of apoptosis. Epinephrine inhibited
      apoptosis induced by the P2X7 receptor ligand 2',3'-0-(4-benzoylbenzoyl)-ATP, by
      attenuation of P2X7 receptor plasma membrane pore formation. Cotreatment with EGF
      facilitated epinephrine effect via a phosphoinositide 3-kinase-dependent
      mechanism. CaSki cells express the beta2-adrenoceptor, and the epinephrine
      antiapoptotic effect could be mimicked by beta2-adrenoceptor agonists and by
      activators of adenylyl cyclase. Likewise, the effect could be blocked by beta2
      adrenoceptor blockers and by the inhibitor of protein kinase-A H-89. Western
      immunoblot analysis revealed that epinephrine decreased the levels of the
      glycosylated 85-kDa form of the P2X7 receptor and increased receptor degradation,
      and that EGF potentiated these effects of epinephrine. EGF did not affect
      cellular levels of the beta2-adrenoceptor. In contrast, EGF, acting via the EGF
      receptor, augmented beta2-adrenoceptor recycling, and it inhibited beta2
      adrenoceptor internalization via a phosphoinositide 3-kinase-dependent mechanism.
      We conclude that, in cervical epithelial cells, EGF has a dual role: as mitogen,
      acting via the MAPK/MAPK kinase pathway, and as an antiapoptotic factor by
      facilitating epinephrine effect and resulting in greater expression of beta2
      adrenoceptors in the plasma membrane. These findings underscore a novel signaling
      network of communication between the receptor tyrosine kinases, the G protein
      coupled receptors, and the purinergic P2X7 receptor.

PMID- 15459116
TI  - Dissociation between iodide-induced thyroiditis and antibody-mediated
      hyperthyroidism in NOD.H-2h4 mice.
AB  - NOD.H-2h4 mice are genetically predisposed to thyroid autoimmunity and
      spontaneously develop thyroglobulin autoantibodies (TgAb) and thyroiditis. Iodide
      administration enhances TgAb levels and the incidence and severity of
      thyroiditis. Using these mice, we investigated the interactions between TSH
      receptor (TSHR) antibodies induced by vaccination and spontaneous or iodide
      enhanced thyroid autoimmunity (thyroiditis and TgAb). Mice were immunized with
      adenovirus expressing the TSHR A-subunit (or control adenovirus). Thyroid
      antibodies, histology, and serum thyroxine levels were compared in animals on a
      regular diet or on a high-iodide diet (0.05% NaI-supplemented water). Thyroiditis
      severity and TgAb levels were enhanced by iodide administration and were
      independent of the type of adenovirus used for immunization. In contrast, TSHR
      antibodies, measured by TSH-binding inhibition, thyroid-stimulating activity, and
      TSH-blocking activity, were induced in the majority of animals immunized with
      TSHR (but not control) adenovirus and were unaffected by dietary iodide. The
      NOD.2h4 strain of mice was less susceptible than BALB/c or BALB/k mice to TSHR
      adenovirus-induced hyperthyroidism. Nevertheless, hyperthyroidism developed in
      approximately one third of TSHR adenovirus-injected NOD.2h4 mice. This
      hyperthyroidism was suppressed by a high-iodide diet, probably by a nonimmune
      mechanism. The fact that inducing an immune response to the TSHR had no effect on
      thyroiditis raises the possibility that the TSHR may not be the target involved
      in the variable thyroiditis component in some humans with Graves' disease.

PMID- 15459117
TI  - Gonadotropin-induced delta14-reductase and delta7-reductase gene expression in
      cumulus cells during meiotic resumption of porcine oocytes.
AB  - Progesterone is produced from cholesterol in cumulus cells during meiotic
      resumption of porcine oocytes. In follicular cells, it has been shown that
      exogenous lipoprotein-bound cholesterol ester can be used for steroid hormone
      production. However, in serum-free medium, progesterone is also secreted by FSH-
      and LH-stimulated cumulus-oocyte complexes, suggesting that progesterone could be
      produced from de novo synthesized cholesterol in cumulus cells. In the present
      study, we investigated the expression of Delta14-reductase and Delta7-reductase,
      which are the members of the superfamily that converts acetyl-CoA to cholesterol
      in cumulus cells. The expression of both genes was analyzed by RT-PCR. Both
      Delta14-reductase mRNA and Delta7-reductase mRNA in cumulus cells, cultured until
      4 h, were under the level of detection limit. In response to gonadotropins, both
      mRNA levels were dramatically up-regulated, reaching a maximum at 20 h. To
      clarify the role of induced enzymes in cumulus cells, cumulus-oocyte complexes
      were cultured with either Delta14-reductase inhibitor, AY9944-A-7, or Delta7
      reductase inhibitor, BM15.766. The results indicated that these inhibitors
      significantly suppressed the progesterone production in cumulus cells and meiotic
      progression of oocytes. The inhibitory effects reached a maximum at 1 microM
      AY9944-A-7 or 20 microM BM15.766. The addition of 20 ng/ml progesterone overcame
      the inhibitory effects of both drugs on meiotic resumption of oocytes. These
      results imply that gonadotropin-induced expression and function of Delta14
      reductase and Delta7-reductase in cumulus cells contribute to oocyte meiotic
      resumption via a progesterone-dependent pathway.

PMID- 15459118
TI  - The role of central glucagon-like peptide-1 in mediating the effects of visceral
      illness: differential effects in rats and mice.
AB  - In rats, central administration of glucagon-like peptide-1 (GLP-1) elicits
      symptoms of visceral illness like those caused by the toxin lithium chloride
      (LiCl), including anorexia, conditioned taste aversion (CTA) formation, and
      neural activation in the hypothalamus and hindbrain including activation of
      brainstem preproglucagon cells. Most compellingly, pharmacological antagonists of
      the GLP-1 receptor (GLP-1R) block several effects of LiCl in rat. The major goal
      of these experiments was to further test the hypothesis that the central nervous
      system GLP-1 system is critical to the visceral illness actions of LiCl by using
      mice with a targeted disruption of the only described GLP-1R. First, we observed
      that, like the rat, LiCl activates preproglucagon neurons in wild-type mice.
      Second, GLP-1R -/- mice demonstrated normal anorexic and CTA responses to LiCl.
      To test the possibility that alternate GLP-1Rs mediate aversive effects, we
      examined the ability of GLP-1 to produce a CTA in GLP1R -/- mice. Although
      lateral ventricular GLP-1 produced a CTA in wild-type mice, it did not produce a
      CTA in GLP-1R -/- mice. Furthermore, the same GLP-1R antagonist that can block
      the aversive effects of LiCl in the rat failed to do so in the mouse. These
      results support the conclusion that in mouse, unlike in rat, GLP-1R signaling is
      not required for the visceral illness response to LiCl. Such species differences
      are an important consideration when comparing results from rat and mouse studies.

PMID- 15459119
TI  - Pancreatic islet adaptation to fasting is dependent on peroxisome proliferator
      activated receptor alpha transcriptional up-regulation of fatty acid oxidation.
AB  - The cellular response to fasting and starvation in tissues such as heart,
      skeletal muscle, and liver requires peroxisome proliferator-activated receptor
      alpha (PPARalpha)-dependent up-regulation of energy metabolism toward fatty acid
      oxidation (FAO). PPARalpha null (PPARalphaKO) mice develop hyperinsulinemic
      hypoglycemia in the fasting state, and we previously showed that PPARalpha
      expression is increased in islets at low glucose. On this basis, we hypothesized
      that enhanced PPARalpha expression and FAO, via depletion of lipid-signaling
      molecule(s) for insulin exocytosis, are also involved in the normal adaptive
      response of the islet to fasting. Fasted PPARalphaKO mice compared with wild-type
      mice had supranormal ip glucose tolerance due to increased plasma insulin levels.
      Isolated islets from the PPARalpha null mice had a 44% reduction in FAO, normal
      glucose use and oxidation, and enhanced glucose-induced insulin secretion. In
      normal rats, fasting for 24 h increased islet PPARalpha, carnitine
      palmitoyltransferase 1, and uncoupling protein-2 mRNA expression by 60%, 62%, and
      82%, respectively. The data are consistent with the view that PPARalpha, via
      transcriptionally up-regulating islet FAO, can reduce insulin secretion, and that
      this mechanism is involved in the normal physiological response of the pancreatic
      islet to fasting such that hypoglycemia is avoided.

PMID- 15459121
TI  - Stimulation of cortisol release by the N terminus of teleost parathyroid hormone
      related protein in interrenal cells in vitro.
AB  - The mode of action of PTHrP in the regulation of sea bream (Sparus auratus)
      interrenal cortisol production was studied in vitro using a dynamic superfusion
      system. Piscine (1-34)PTHrP (10(-6)-10(-11) M) stimulated cortisol production in
      a dose-dependent manner. The ED50 of (1-34)PTHrP was 2.8 times higher than that
      of (1-39)ACTH, and maximum increase in cortisol production in response to 10(-8)
      M of (1-34)PTHrP was approximately 7-fold lower than for 10(-8) M of (1-39)ACTH.
      In contrast to (1-34)PTHrP, piscine (10-20)PTHrP, (79-93)PTHrP, and (100
      125)PTHrP (10(-9)-10(-7) M) did not stimulate cortisol production. The effect of
      piscine (1-34)PTHrP on cortisol production was abolished by N-terminal peptides
      in which the first amino acid (Ser) was absent and by simultaneous addition of
      inhibitors of the adenylyl cyclase-protein kinase A and phospholipase C-protein
      kinase C intracellular pathways but not by each separately. The PTHrP-induced
      signal transduction was further investigated by measurements of cAMP production
      and [H3]myo-inositol incorporation in an interrenal cell suspension. Piscine (1
      34)PTHrP increased cAMP and total inositol phosphate accumulation, which is
      indicative that the mechanism of action of PTHrP in interrenal tissue involves
      the activation of both the adenylyl cyclase-cAMP and phospholipase C-inositol
      phosphate signaling pathways. These results, together with the expression of mRNA
      for PTHrP and for PTH receptor (PTHR) type 1 and PTHR type 3 receptors in sea
      bream interrenal tissue, suggest a specific paracrine or autocrine steroidogenic
      action of PTHrP mediated by the PTHRs.

PMID- 15459120
TI  - Epidermal growth factor family members: endogenous mediators of the ovulatory
      response.
AB  - Previous studies showed that epidermal growth factor (EGF) and TGFalpha mimic the
      action of LH on the resumption of oocyte maturation. We tested whether EGF-like
      agents, such as amphiregulin (AR), epiregulin (ER), and betacellulin (BTC), also
      mediate the LH stimulation of the ovulatory response in the rat. LH induced
      transient follicular expression of AR, ER, and BTC mRNA, reaching a maximum after
      3-h incubation. Furthermore, the addition of ER, AR, and BTC to the culture
      medium could mimic some of LH actions. AR and ER fully simulated LH-induced
      resumption of meiosis in vitro, whereas BTC was less effective. To study the
      putative involvement of EGF-like factors in mediation of LH signal, the effect of
      the EGF receptor kinase inhibitor AG1478 was tested. When added with LH, AG1478,
      but not its inactive analog AG43, reduced EGF receptor phosphorylation and oocyte
      maturation compared with follicles treated with LH only. In addition to the
      inhibition of resumption of meiosis, AG1478 administration into the bursa (3
      microg/bursa) resulted in 51% (P < 0.0005) inhibition of ovulation in the treated
      ovaries, compared with the untreated contralateral ones, as well as to the
      vehicle-treated ovaries (P < 0.02). LH, as well as ER, induced the expression of
      genes associated with the ovulatory response like rat hyaluronan synthase-2,
      cyclooxygenase-2, and TNFalpha-stimulated gene 6 mRNA, whereas AG1478 inhibited
      this effect of LH. Release of EGF-like factors from the membrane is dependent on
      activated metalloproteases. Indeed, Galardin, a broad-spectrum metalloprotease
      inhibitor, but not a specific matrix metalloprotease 2 and 9 inhibitor,
      suppressed meiotic maturation induced by LH. Conversely, meiotic maturation
      induced by ER was not affected by Galardin, thus, supporting the notion that LH
      releases follicular membrane-bound EGF-like agents. In summary, EGF-like factors
      such as ER, AR, and BTC seem to mediate, at least partially, the LH stimulation
      of oocyte maturation, ovulatory enzyme expression, and ovulation.

PMID- 15459122
TI  - Male marmoset monkeys express an adrenal fetal zone at birth, but not a zona
      reticularis in adulthood.
AB  - Neonatal human males produce high levels of dehydroepiandrosterone (DHEA) and its
      sulfo-conjugated form (DS) that decline within a few months of birth, due to
      regression of the adrenal fetal zone (FZ). Adult male humans and rhesus monkeys
      produce C19 steroids in abundance from the adrenal zona reticularis (ZR). Male
      marmoset monkeys produce DS at birth, but unlike humans and rhesus monkeys, do
      not produce comparable amounts of DHEA and DS in adulthood. To determine whether
      male marmosets express a functional ZR in adulthood, we examined adult and
      neonatal male marmosets for the presence of a ZR and FZ, respectively. Exogenous
      ACTH failed to stimulate DHEA or DS in adults, and dexamethasone treatment failed
      to suppress DHEA and DS, although cortisol levels changed as expected. In
      steroidogenic tissues, the key proteins necessary to synthesize C19 steroids from
      pregnenolone are P450c17, 3beta-hydroxysteroid dehydrogenase (3beta-HSD),
      nicotinamide adenine dinucleotide phosphate (reduced) oxido-reductase cytochrome
      P450 (reductase), and cytochromeb5 (cytb5). Adult adrenal cross sections showed
      P450c17 and reductase protein expression throughout the cortex but showed no
      expected decrease in 3beta-HSD and increase in cytb5 in the innermost region.
      Western analysis confirmed these data, demonstrating comparable P450c17
      expression to rhesus monkeys, but not cytb5. HPLC analysis revealed similar
      17alpha-hydroxylase action on pregnenolone for adult marmoset and rhesus adrenal
      microsomes but greatly diminished 17,20-lyase activity in marmosets. Neonatal
      marmoset adrenals exhibited staining indicative of a putative FZ (with P450c17,
      reduced 3beta-HSD and increased cytb5). We conclude that neonatal marmosets
      exhibit a C19 steroid-secreting FZ similar to humans, but adult males fail to
      acquire a functional ZR.

PMID- 15459123
TI  - Unraveling the amyloid associated with human medullary thyroid carcinoma.
AB  - Medullary thyroid carcinoma (MTC) is associated with amyloid deposition in the
      surrounding tissues. MTC-positive tumor thyroid tissues surgically removed from
      patients were used in our study to extract amyloid. We tested the MTC extracts
      for the presence of amyloid by measuring fold enhancement of thioflavin T
      fluorescence. Transmission electron microscopic study and atomic force microscopy
      of MTC patient extracts revealed typical amyloid fibrils. Matrix-assisted laser
      desorption ionization-time of flight mass spectrometric analysis demonstrated
      full-length calcitonin as the constituent of the MTC amyloid from seven patients.
      Our results unequivocally demonstrated that full-length calcitonin is the sole
      constituent of amyloid in MTC.

PMID- 15459124
TI  - Werner syndrome cells escape hydrogen peroxide-induced cell proliferation arrest.
AB  - Werner syndrome (WS) is a rare disease caused by the lack of a functional nuclear
      WS protein (WRN). WS is characterized by the early onset of premature aging signs
      and a high incidence of sarcomas. WS diploid fibroblasts have a short life span
      and extensive genomic instability. Mammalian cells are continuously exposed to
      reactive oxygen species (ROS), which represent human mutagens and are thought to
      be a major contributor to the aging process. Hydrogen peroxide (H2O2) is a common
      ROS intermediate generated by various forms of oxidative stress. In response to
      H2O2-induced DNA damage, normal human diploid fibroblasts follow a pathway
      leading to irreversible proliferation arrest and premature senescence. Here we
      show that in contrast to normal human fibroblasts, WS diploid fibroblasts
      continue proliferating after extensive H2O2-induced DNA damage and accumulate
      oxidative DNA lesions. A direct role of WRN in this abnormal cellular response to
      H2O2 is demonstrated by interfering with WRN expression in normal human
      fibroblasts. We propose a role for WRN in the detection and/or processing of
      oxidative DNA lesions and in cellular responses to H2O2 as they relate to some of
      the phenotypical aspects of WS cells.

PMID- 15459125
TI  - Emigration and immigration of mesenchymal cells: a multicultural airway wall.

PMID- 15459126
TI  - Adrenomedullin: a smart road from pheochromocytoma to treatment of pulmonary
      hypertension.

PMID- 15459127
TI  - Paediatric interstitial lung disease: not just kid's stuff.

PMID- 15459128
TI  - Characterisation of post-pneumonectomy lung growth in adult mice.
AB  - A model of inducible expansion of the gas exchange area in adult mice would be
      ideal for the investigation of molecular determinants of airspace regeneration in
      vivo. Therefore, the post-pneumonectomy (post-PNX) compensatory lung growth in
      adult C57BL/6 mice was characterised in this study. Mice underwent left-sided
      PNX. Right lung volume was assessed on days 1, 3, 5, 7, 10 and 21 after PNX, and
      total DNA and cellular proliferation of the right lung were determined. Lung
      histology was studied using immunohistochemistry and quantitatively characterised
      by detailed stereological investigations. Pulmonary function was assessed using a
      mouse body-plethysmograph. Following PNX, right-lung volume rapidly restored the
      initial volume of left and right lung. Total DNA increased significantly over 21
      days and equalled the total DNA amount of both lungs in the control mice. Septal
      cell proliferation significantly increased after PNX, and included endothelial
      cells, epithelial cells, smooth muscle cells and fibroblasts. Stereological
      investigations of left and right control lungs versus right lungs 21 days after
      PNX indicated complete restoration of body mass-specific alveolar surface area.
      Pulmonary function testing showed marked alteration at 3 days and normalisation
      at 21 days post-PNX. In conclusion, well reproducible reconstitution of alveolar
      gas-exchange surface based on septal tissue expansion may be provoked by
      pneumonectomy in adult mice.

PMID- 15459129
TI  - Endobronchial ultrasonography with guide-sheath for peripheral pulmonary lesions.
AB  - The usefulness of endobronchial ultrasonography (EBUS) with guide-sheath (GS) as
      a guide for transbronchial biopsy (TBB) for diagnosing peripheral pulmonary
      lesions (PPL)s and for improving diagnostic accuracy was evaluated in this study.
      EBUS-GS-guided TBB was performed in 24 patients with 24 PPLs of < or =30 mm in
      diameter (average diameter=18.4 mm). A 20-MHz radial-type ultrasound probe,
      covered with GS was inserted via a working bronchoscope channel and advanced to
      the PPL in order to produce an EBUS image. The probe with the GS was confirmed to
      reach the lesion by EBUS imaging and X-ray fluoroscopy. When the lesion was not
      identified on the EBUS image, the probe was removed and a curette was used to
      lead the GS to the lesion. After localising the lesion, the probe was removed,
      and TBB and bronchial brushing were performed via the GS. Nineteen peripheral
      lesions (79.2%) were visualised by EBUS. All patients whose PPLs were visible on
      EBUS images subsequently underwent an EBUS-GS-guided diagnostic procedure. A
      total of 14 lesions (58.3%) were diagnosed. Even when restricted to PPLs <20 mm
      in diameter, the diagnostic sensitivity was 53%. In conclusion, endobronchial
      ultrasonography with guide sheath-guided transbronchial biopsy was feasible and
      effective for diagnosing peripheral pulmonary lesions.

PMID- 15459130
TI  - HRCT lung abnormalities are not a surrogate for exercise limitation in
      bronchiectasis.
AB  - In paediatric bronchiectasis, there has been limited work on the relationship
      between disease severity as assessed by exercise limitation and high resolution
      computed tomography (HRCT). An observational study was performed on 36 children
      who completed a questionnaire, physical examination, spirometry and sputum
      analysis, followed by a low dose of radiation protocol chest computed tomography
      (CT) scan and cycle ergometry incremental exercise test. A modified Bhalla score
      was used to score the HRCT abnormalities. The exercise variables used to assess
      functional status were heart rate, oxygen consumption, oxygen saturations and
      time of exercise. The results were compared with established normal paediatric
      values. The median (range) age of the children was 13 yrs (10.6-17.1). Age, sex,
      height, weight or pubertal status were equally distributed between the children
      with cystic fibrosis (CF) or non-CF bronchiectasis. The children with non-CF
      bronchiectasis had a lower median forced expiratory volume in one second %
      predicted than the children with CF (69% versus 76%, respectively). The
      distribution of lung disease differed between the two groups. The children with
      CF bronchiectasis had predominantly right upper lobe disease, and scored higher
      for the presence and extent of bronchiectasis. Otherwise, there was no
      statistical difference in the overall CT score or the individual CT parameters
      between the groups. There was evidence of exercise limitation in both CF and non
      CF bronchiectasis compared to normal children. No consistent relationships were
      identified between the lung function parameters, HRCT findings or exercise
      parameters in either disease group. In this study, high resolution computed
      tomography features were not found to be markers of exercise capacity. As
      spirometry, high resolution computed tomography features and exercise testing
      give different information in children with cystic fibrosis and non-cystic
      fibrosis bronchiectasis, the current authors suggest all three may be required
      for the comprehensive assessment of respiratory status.

PMID- 15459131
TI  - Extracellular matrix regulates human airway smooth muscle cell migration.
AB  - Extracellular matrix proteins regulate the survival and proliferation of smooth
      muscle cells. Their effect on airway smooth muscle cell migration is not known.
      Their role in leukotriene-primed (0.1 microM leukotriene E4) chemotaxis of
      cultured human airway smooth muscle cells towards platelet-derived growth factor
      BB (1 ng.mL(-1)) was investigated. Migration of cells was greater on membranes
      coated with collagens III and V and fibronectin compared to collagen I, elastin
      and laminin (all 10 microg.mL(-1)). Concentration-dependent promotion of
      migration was observed on collagen I (1,000>10 microg.mL(-1)), which was
      associated with increased phosphorylation of Src kinase. This was not observed on
      laminin or elastin. The role of Src kinase was further confirmed by demonstrating
      that its inhibitor, PP1 analogue (1 microM), inhibited chemotaxis. Collagen I
      itself was not a chemoattractant; however, haptokinesis was observed when cells
      were primed with leukotriene E4, and haptotaxis when cells were primed with
      platelet-derived growth factor. The priming effect of leukotrienes on chemotaxis
      was not elicited by promoting adhesion, increasing surface expression of beta1,
      alphav and alpha5 integrin, or Src kinase phosphorylation. These experiments
      demonstrate that the extracellular matrix, along with growth factors and
      cysteinyl leukotrienes, can regulate human airway smooth muscle cell migration.
      This may be relevant in the remodelling process in chronic airway diseases, such
      as asthma.

PMID- 15459132
TI  - Down-regulation of mast cell activation and airway reactivity in diabetic rats:
      role of insulin.
AB  - Hormones play a modulating role in allergic inflammation. An inverse relationship
      between atopy and diabetes mellitus was reported. The mechanisms regulating this
      interaction are not completely understood. This study examined whether insulin
      influences mast cell activation following antigen challenge in rats. The
      experimental design included alloxan-induced diabetic rats and matching controls.
      Experiments were performed 30 days after alloxan injection. The animals were
      sensitised by s.c. injection of ovalbumin (OA) and aluminium hydroxide. OA
      induced airway contraction, morphometric analysis of airway mast cells and tissue
      histamine quantification were evaluated in the isolated main bronchus and
      intrapulmonary bronchus upon exposure to antigen in vitro. Relative to controls,
      a reduced contraction to OA was observed in bronchial segments isolated from
      diabetic rats. This was accompanied by a 50% reduction in the number of
      degranulated mast cells and in histamine release. A complete recovery of the
      impaired responses was observed under the influence of insulin. In conclusion,
      the data suggested that insulin might modulate the controlling of mast cell
      degranulation; therefore, the early-phase response to antigen provocation, which
      represents a new insight into a better understanding of the mechanisms, accounted
      for the decreased risk of asthma among type-1 diabetic patients.

PMID- 15459133
TI  - Role and regulation of interleukin-1 molecules in pro-asthmatic sensitised airway
      smooth muscle.
AB  - Interleukin (IL)-1beta is a pleiotropic, pro-inflammatory cytokine that has been
      importantly implicated in driving the inflammatory response and resultant changes
      in airway smooth muscle (ASM) responsiveness in asthma. IL-1beta belongs to a
      family of molecules, known as the IL-1 axis, which exert both pro- and anti
      inflammatory effects. Since dysregulation of IL-1 axis molecules may be critical
      in the pathobiology of asthma, the present study examined the expression and
      activation of both the inhibitory and stimulatory IL-1 axis molecules in human
      ASM cells and their roles in modulating cytokine and immunoglobulin (Ig)E immune
      complex (IgE cx)-mediated changes in rabbit ASM constrictor and relaxant
      responsiveness. The results demonstrate the following. 1) Pre-treatment of
      isolated rabbit tracheal rings with the inhibitory IL-1 axis members, IL-1
      receptor antagonist and IL-1 type-II receptor abrogated both IL-5- and IgE cx
      induced changes in ASM responsiveness. 2) Administration of IL-5, IL-1beta and
      IgE cxs to human ASM cells increased mRNA and protein expressions of both
      stimulatory and inhibitory IL-1 axis molecules. 3) The time course of IL-5
      induced IL-1 axis molecule expression preceded that of both IL-1beta and IgE
      immune cxs. Collectively, these findings suggest that modulation at the level of
      the interleukin-1 axis of molecules may have significant therapeutic potential in
      the treatment of asthma.

PMID- 15459134
TI  - Country-specific cost-effectiveness of early intervention with budesonide in mild
      asthma.
AB  - Early intervention with budesonide is an effective strategy for mild persistent
      asthma, which has been shown to provide additional clinical benefits at a low
      incremental cost using USA cost data. The present authors analysed whether this
      strategy would be cost-effective using cost data for other countries. Based on
      the 3-yr prospective, randomised, double-blind inhaled Steroid Treatment As
      Regular Therapy (START) in early asthma study (comparing budesonide and placebo
      combined with usual asthma therapy), the cost-effectiveness was estimated
      separately for eight different countries, from both healthcare payer and societal
      perspectives, of adding budesonide to usual asthma therapy. Local unit costs were
      applied to data for the total trial population. Incremental cost-effectiveness
      ratios (ICER) were estimated as cost per symptom-free day (SFD) gained.
      Budesonide increased SFDs by an average of 14.1 days annually. From a healthcare
      payer perspective, budesonide would reduce the total cost of asthma care in
      Australia. In Sweden, Canada, France, Spain, UK, China and the USA, the ICER
      ranged from US$2.4-11.3 per SFD. From a societal perspective, budesonide would be
      cost-saving in Australia, Canada and Sweden. In conclusion, for countries where
      costs with budesonide are higher, the policy implication has to be determined by
      that health system's willingness to pay for an additional symptom-free day.
      However, where budesonide therapy increases symptom-free days and reduces total
      costs, the policy conclusion clearly favours early intervention.

PMID- 15459135
TI  - Lung fibroblasts from patients with emphysema show a reduced proliferation rate
      in culture.
AB  - Emphysema is characterised by a loss of alveolar structure, as reflected in
      elastic recoil and gas exchange. As fibroblasts play a key role in the
      maintenance of structure, the current authors hypothesised that their
      proliferation might be constitutively impaired in lung emphysema. Using explant
      cultures, lung fibroblasts were obtained from resected lungs of 10 patients with
      emphysema (median forced expiratory volume in one second (FEV1) 40% predicted)
      and 10 control patients (FEV1, 95% pred). The doubling time (DT) was measured
      over 4 days under standard conditions (10% foetal calf serum) prior and after
      cryopreservation. Additionally, in seven samples per group the total population
      doubling level (PDL) was determined. In emphysema, mean+/-sem DT was 33.6+/-2.8 h
      compared with 24.8+/-1.4 h in controls. The differences in DT were preserved
      after cryopreservation. Groups also differed in the initial slope of the PDL plot
      during long-term culture (up to 35 days). However, the median (range) maximum PDL
      did not differ significantly between groups (13.8 (7.4-22.6) versus 20.2 (11.2
      25.5)). The current authors, therefore, suggest that the reduced proliferation
      rate in vitro of lung fibroblasts from patients with emphysema reflects a
      persistent, intrinsic failure of cellular replacement and maintenance in this
      disease, possibly in relation to pre-term aging.

PMID- 15459136
TI  - Relationship between exercise desaturation and pulmonary haemodynamics in COPD
      patients.
AB  - Pulmonary hypertension (PH) in patients with chronic obstructive pulmonary
      disease (COPD) has traditionally been explained as an effect of hypoxaemia.
      Recently, other mechanisms, such as arterial remodelling caused by inflammation,
      have been suggested. The aim of this study was to investigate whether exercise
      induced PH (EIPH) could occur without concurrent hypoxaemia, and whether exercise
      induced hypoxaemia (EIH) was regularly accompanied by increased pulmonary artery
      pressure or pulmonary vascular resistance index (PVRI). Pulmonary haemodynamics
      in 17 patients with COPD of varying severity, but with no or mild hypoxaemia at
      rest, were examined during exercise equivalent to the activities of daily living
      (ADL) and exhaustion. EIPH occurred in 65% of the patients during ADL exercise.
      Pulmonary arterial pressure during exercise was negatively correlated with
      arterial oxygen tension, but EIPH was not invariably accompanied by hypoxaemia.
      Conversely, EIPH was not found in all patients with EIH. The resting PVRI was
      negatively correlated with arterial oxygen tension during ADL exercise, but an
      elevated PVRI without EIH occurred in 35% of the patients. In conclusion,
      exercise-induced pulmonary hypertension occurred during exercise equivalent to
      the activities of daily living in chronic obstructive pulmonary disease patients
      with no or mild hypoxaemia at rest. Although pulmonary artery pressure and
      arterial oxygen tension were negatively correlated during exercise, a consistent
      relationship between hypoxaemia and pulmonary hypertension could not be
      demonstrated. This may indicate that mechanisms other than hypoxaemia contribute
      significantly in the development of pulmonary hypertension in these patients.

PMID- 15459137
TI  - The effect of fluticasone on the airway inflammatory response to organic dust.
AB  - Exposure to organic dust in a swine house causes acute airway inflammation and
      increased bronchial responsiveness to methacholine in healthy subjects. The aim
      of this study was to investigate whether an inhaled glucocorticoid, fluticasone
      propionate, alters the acute airway responses induced by exposure in a swine
      barn. In 15 healthy subjects, analysis of nasal lavage fluids, serum samples and
      bronchial methacholine responsiveness were performed before and after exposure to
      organic dust in a swine house for 3 h. Seven subjects received fluticasone
      propionate (500 microg b.i.d. by inhalation and 100 microg intranasally once
      daily) and eight subjects received placebo during the 2 weeks prior to exposure.
      Post-exposure plasma interleukin (IL)-6 levels and body temperature were
      significantly lower in the fluticasone group than in the placebo group.
      Intranasally administered fluticasone propionate significantly attenuated the
      plasma protein (assessed as albumin concentrations) leakage and IL-8 and tumour
      necrosis factor-alpha response induced by exposure. Fluticasone propionate
      inhalation exerted no influence on the increased bronchial responsiveness to
      methacholine induced by exposure. In conclusion, glucocorticoid treatment
      attenuated the inflammatory response to inhaled organic dust without influencing
      the increased bronchial responsiveness to methacholine.

PMID- 15459138
TI  - Intranasal steroids decrease eosinophils but not mucin expression in nasal
      polyps.
AB  - Increased mucin expression is a feature of nasal polyposis. Corticosteroids
      reduce polyp size and symptoms, but their effect on mucin production remains
      unknown. In this study, the effects of intranasal corticosteroids on MUC5AC mucin
      expression, nasal resistance, eosinophil and neutrophil infiltration, epidermal
      growth factor receptor (EGFR), interleukin (IL)-8, and tumour necrosis factor
      (TNF)-alpha expression was assessed in nasal polyps. In nine subjects, one nasal
      polyp was removed surgically before treatment and another was removed after 8
      weeks of intranasal fluticasone (400 microg.day(-1)). Tissues were processed for
      in situ hybridisation and immunohistochemical staining. Described effects of
      fluticasone on nasal polyps (reduction in nasal resistance and in eosinophil
      infiltration) were evaluated. Morphometric analysis was performed to assess the
      effect of fluticasone on epithelial-, MUC5AC-, EGFR- and IL-8-stained areas, TNF
      alpha-stained cells, and neutrophil numbers. Treatment with fluticasone decreased
      nasal resistance and intra-epithelial eosinophils. The MUC5AC-stained area in the
      epithelium was unchanged by treatment; MUC5AC mRNA expression was unaffected by
      treatment. EGFR-stained area, intra-epithelial neutrophil numbers, IL-8 and TNF
      alpha expression were also unchanged by therapy. Intranasal fluticasone was
      effective in decreasing nasal airflow resistance and intra-epithelial eosinophils
      but had no effect on mucin or epidermal growth factor receptor expression or on
      neutrophil recruitment.

PMID- 15459139
TI  - Sarcoidosis: social predictors of severity at presentation.
AB  - To determine relationships among social predictors and sarcoidosis severity at
      presentation, demographic characteristics, socioeconomic status, and barriers to
      care, A Case-Control Etiologic Study of Sarcoidosis (ACCESS) was set up. Patients
      self-reported themselves to be Black or White and were tissue-confirmed incident
      cases aged > or =l8-yrs-old (n=696) who had received uniform assessment
      procedures within one of 10 medical centres and were studied using standardised
      questionnaires and physical, radiographical, and pulmonary function tests.
      Severity was measured by objective disease indicators, subjective measures of
      dyspnoea and short form-36 subindices. The results of the study showed that lower
      income, the absence of private or Medicare health insurance, and other barriers
      to care were associated with sarcoidosis severity at presentation, as were race,
      sex, and age. Blacks were more likely to have severe disease by objective
      measures, while women were more likely than males to report subjective measures
      of severity. Older individuals were more likely to have severe disease by both
      measures. In conclusion, it was found that low income and other financial
      barriers to care are significantly associated with sarcoidosis severity at
      presentation even after adjusting for demographic characteristics of race, sex,
      and age.

PMID- 15459140
TI  - An increase in exhaled nitric oxide is not associated with activity in pulmonary
      sarcoidosis.
AB  - Exhaled nitric oxide (eNO) concentration measurement may permit the noninvasive
      estimation of the severity of airways inflammation in respiratory tract diseases.
      The aim of this study was to evaluate the correlation between eNO concentration
      and the activity of sarcoidosis, its radiographic staging and lung function
      abnormalities. eNO concentration was measured using a chemiluminescent analyser
      in 27 patients with sarcoidosis and 11 control subjects. The mean eNO
      concentration in patients with sarcoidosis was significantly higher (6.7+/-0.50
      parts per billion (ppb)) than that in the control group (5.17+/-0.73 ppb). eNO
      concentration was similar in radiographic stage I, II and III patients (6.53,
      7.32 and 6.24 ppb, respectively). No significant difference was found in eNO
      concentration between the patients with active and inactive disease. Nor did eNO
      concentration differ between the patients with and without indication for
      therapy. There was no significant correlation between eNO concentration and
      forced vital capacity or bronchoalveolar lavage fluid lymphocyte and macrophage
      counts. There was a weak correlation between eNO concentration and single-breath
      carbon monoxide diffusing capacity of the lung. Exhaled nitric oxide
      concentration is elevated in patients with sarcoidosis. This concentration does
      not depend on the radiographic staging, activity or progression of the disease.

PMID- 15459141
TI  - Brief adrenomedullin inhalation leads to sustained reduction of pulmonary artery
      pressure.
AB  - The effect of aerosolised adrenomedullin (ADM), a potent vasodilator peptide, on
      pulmonary artery pressure was studied for 24 h in a surfactant-depleted piglet
      model. Animals received either aerosolised ADM (50 ng.kg(-1).min(-1), ADM, n=6),
      or aerosolised normal saline solution (control, n=6). Aerosol therapy was
      performed for a 2 h treatment period followed by a 22 h observation period.
      Ventilator settings were adapted to keep arterial oxygen tension and carbon
      dioxide arterial tension between 13.3-14.6 kPa and 4.9-5.7 kPa, respectively.
      Aerosolised ADM reduced mean pulmonary artery pressure (MPAP) compared with the
      control group (end-point median 24 h after therapy start: DeltaMPAP -14.0 versus 
      8.0 mmHg; 23.5 h after therapy start). After therapy start, mean systemic
      arterial pressure (MAP) was not significantly different between the groups (end
      point median: MAP ADM 70 (61/74) versus control 72 (54/81) mmHg). Endothelin-1, a
      potent pulmonary vasoconstrictor, is regulated by ADM via cAMP. Twenty two hours
      after inhalation of aerosolised ADM, endothelin-1 mRNA in lung tissue and
      endothelin-1 protein expression in pulmonary arteries was reduced compared with
      controls (median semi-quantitative immunhistochemical score: ADM 0.21, control
      0.76). Aerosolised adrenomedullin significantly reduced mean pulmonary artery
      pressure independently of arterial oxygen tension.

PMID- 15459142
TI  - Setting of noninvasive pressure support in young patients with cystic fibrosis.
AB  - The aim of the current study was to compare a clinical noninvasive method of
      setting up noninvasive pressure support ventilation (PS-NI) in young patients
      with cystic fibrosis (CF), based on parameters such as breathing frequency,
      arterial oxygen saturation and comfort rating, with a more invasive method (PS-I)
      targeted at optimising unloading of the inspiratory muscles and enhancing patient
      ventilator synchronisation. PS-NI and PS-I were compared in random order in 10
      children with CF. PS-NI differed from PS-I with regard to the level of
      inspiratory pressure (n=5), rate of inspiratory pressurisation (n=1), inspiratory
      trigger sensitivity (n=2) and expiratory trigger sensitivity (n=5). Although both
      methods modified breathing pattern, improved oxygen saturation and reduced
      diaphragmatic pressure time product (450+/-91 cmH2O.s(-1).min(-1) during
      spontaneous breathing, and 129+/-125 and 104+/-75 cmH2O.s(-1).min(-1) during PS
      NI and PS-I, respectively), patient-ventilator synchrony and patient comfort were
      enhanced more during PS-I. In young patients with cystic fibrosis, setting up
      pressure support using a clinical noninvasive approach based on easily measurable
      parameters, such as respiratory rate and comfort rating, is as effective as a
      more invasive technique based on unloading of the inspiratory muscles and
      optimising patient-ventilator synchronisation. However, whilst the standard
      clinical method is satisfactory in the majority of patients, more invasive
      measurements should be considered in patients who have difficulty synchronising
      with the ventilator to enhance patient tolerance and compliance.

PMID- 15459143
TI  - Sputum versus bronchoscopy for diagnosis of Pseudomonas aeruginosa biofilms in
      cystic fibrosis.
AB  - The present authors hypothesised that bronchoscopy with protected specimen brush
      may sample biofilm-forming bacteria adherent to the airway wall, whereas
      traditional sputum collection may not. Pseudomonas aeruginosa obtained from
      sputum, bronchoalveolar lavage and protected brush, taken from the right upper
      lung bronchus of 12 adult patients with cystic fibrosis, were compared. Retrieved
      bacteria were genotyped, and grown in planktonic cultures and as biofilms, and
      susceptibilities to individual antibiotics and to antibiotic combinations were
      determined. Bacterial cultures obtained using bronchoscopy did not yield any new
      strains of bacteria that were not also found in sputum. A total of 10 patients
      (83%) had a single strain of P. aeruginosa found using sputum, bronchoalveolar
      lavage and protected brush techniques, and two patients (17%) had two strains
      recovered in sputum, but only one strain was recovered using bronchoscopic
      techniques. Susceptibility to single antibiotics and to antibiotic combinations
      were not different between planktonically or biofilm-grown bacteria derived from
      sputum, as compared to those obtained by bronchoalveolar lavage and protected
      brush. In conclusion, sputum collection provides as much information as
      bronchoscopy for characterising the genotype and antibiotic susceptibility of
      chronic Pseudomonas aeruginosa infection in patients with stable cystic fibrosis.

PMID- 15459144
TI  - Expansion of CCR5+ CD4+ T-lymphocytes in the course of active pulmonary
      tuberculosis.
AB  - Nonsyncytium inducing, macrophage tropic HIV strains predominate in the course of
      active tuberculosis (TB). The present study assesses the expression of CCR5 in
      CD4+ T-lymphocytes from blood and bronchoalveolar lavage (BAL) of TB patients,
      non-TB lung disease controls and healthy controls. Memory (CD45RO+), recently
      activated (CD69+), proliferating (Ki67+) CCR5+ or CCR3+ CD4+ T-lymphocytes were
      determined by multiparametric flow cytometry analysis. Results show that BAL CD4+
      T-lymphocytes expressing CCR5 or CCR3 were significantly increased when compared
      to peripheral blood both in patients and in healthy controls. However, the data
      show that the proportions of peripheral blood CCR5+ CD4+ and CCR3+ CD4+ T
      lymphocytes and BAL CCR5+ CD4+ T-lymphocytes, but not BAL CCR3+ CD4+ T
      lymphocytes, were significantly increased in TB patients. Furthermore, the
      observation that BAL CCR5+ CD4+ T-lymphocytes from TB patients expressed early
      activation markers, were not proliferating and showed down-regulation of CCR5
      expression suggests recruitment and trapping at the site of disease. Altogether,
      these results suggest that the lower respiratory tract mucosa may provide
      cellular targets accessible for efficient transmission of macrophage tropic HIV-1
      variants and that tuberculosis may enhance this phenomenon.

PMID- 15459145
TI  - Cost-effectiveness of full-course oral levofloxacin in severe community-acquired
      pneumonia.
AB  - Oral levofloxacin is as efficient as sequential antibiotic treatment in community
      acquired pneumonia (CAP). The current authors assessed whether oral levofloxacin
      treatment of patients with severe CAP, followed-up for 30 days, would save money.
      Over a 12-month period, 129 hospitalised patients with severe non-intensive care
      unit CAP were randomly assigned to receive either oral levofloxacin or sequential
      antibiotic treatment. Direct and indirect costs were compared over a 30-day
      period from several perspectives. CAP resolved in 71 out of 77 oral levofloxacin
      (92%) and in 34 out of 37 sequential antibiotic treatment patients (92%).
      Patients' characteristics, treatment duration, hospital length of stay and
      mortality were similar in both groups. Drug acquisition costs were 1.7-times
      smaller in oral levofloxacin patients, who were less often transferred to
      rehabilitation centres, but they used more physicians' visits during follow-up
      and their total costs were lower. As only a minority of patients was still
      active, inability to work and, hence, indirect costs were similar in both groups.
      In this study, oral levofloxacin for severe non-intensive care unit community
      acquired pneumonia was equally effective as sequential antibiotic treatment, but
      did not lead to major costs savings except for drug acquisition costs. External
      factors linked with patients' characteristics and/or medical practice are likely
      to play a role and should be addressed.

PMID- 15459146
TI  - Bench testing of auto-adjusting positive airway pressure devices.
AB  - Continuous positive airway pressure devices are routinely used to treat sleep
      breathing disorders. Automated devices that adjust the therapeutic pressure have
      recently been proposed. The utility of such devices is still controversial, as
      rigorous clinical comparisons are difficult to perform as a result of patient and
      device differences. The current authors studied automated devices in a
      respiratory model that was able to mimic upper airway mechanics and to interact
      with pressure adjustment in a closed loop. Five auto-adjusted devices were
      submitted to this model, in order to determine their ability to detect
      respiratory events and adjust pressure accordingly. All apnoeas were suppressed,
      whilst the reaction to repetitive hypopnoeas was dependent on the airflow shape.
      In some devices, repetitive hypopnoeas were changed to flow limitation.
      Artificial snoring caused a pressure increase in four devices, and constant mask
      leak was not systematically compensated. Only one device did not raise pressure
      in response to central apnoeas with opened upper airways. These findings show
      that, in some devices, event classification failed and normal airflow was not
      fully restored, resulting in elevated residual event indices. In conclusion, this
      model is useful in order to reproducibly compare diagnostic and therapeutic
      capacities of commercial devices as a first step, before costly clinical studies.

PMID- 15459147
TI  - Radiofrequency ablation of airway smooth muscle for sustained treatment of
      asthma: preliminary investigations.
AB  - Bronchial thermoplasty is a procedure now being tested in humans for the
      treatment of asthma. Current studies focusing on safety are encouraging. The
      procedure, which causes extensive ablation of airway smooth muscle (ASM), is well
      tolerated, and there is a sustained reduction in airway responsiveness to
      methacholine. Two assumptions underlie the development of this procedure: 1) ASM
      is a vestigial tissue; and 2) that treatment directed at ASM alone will provide
      sustained symptomatic and physiological improvement in asthmatic humans. Even if
      this procedure is efficacious, it must be safe in the long-term. Current studies
      in animals and humans suggest that this is very likely to be the case. While
      bronchial thermoplasty may have a broad application, especially for patients who
      wish for a permanent amelioration of their symptoms or have difficulty adhering
      to medical regimens, the compelling use of this procedure is for patients who are
      inadequately controlled on current drug therapy or who cannot adhere to
      therapeutic regimens. The application of this procedure for the treatment of
      asthma is currently being considered by regulatory agencies, and study centres
      are currently disseminated throughout North America and Europe. Within the next 1
      2 yrs, a profile of the potential role of this therapy in human asthma should be
      developed fully.

PMID- 15459148
TI  - The use of alveolar epithelial type I cell-selective markers to investigate lung
      injury and repair.
AB  - Alveolar epithelial type I cells cover most of the internal surface area of the
      lungs. Ultrastructural studies demonstrate that alveolar epithelial type I cell
      damage is frequently observed in acute and chronic lung diseases. This article
      discusses the use of cell-selective proteins as markers for the investigation of
      injury and repair of the alveolar epithelium. The utility of proteins specific to
      alveolar epithelial type I cells as diagnostic markers of alveolar epithelial
      injury in acute lung injury is considered, and expression of proteins selective
      for alveolar epithelial type I cells in lungs following injury and in fibrosis
      are discussed.

PMID- 15459149
TI  - Lung transplant outcomes: a review of survival, graft function, physiology,
      health-related quality of life and cost-effectiveness.
AB  - The success of lung transplantation has improved over time as evidenced by better
      long-term survival and functional outcomes. Despite the success of this
      procedure, there are numerous problems and complications that may develop over
      the life of a lung transplant recipient. With proper monitoring and treatment,
      the frequency and severity of these problems can be decreased. However,
      significant improvement for the overall outcomes of lung transplantation will
      only occur when better methods exist to prevent or effectively treat chronic
      rejection.

PMID- 15459150
TI  - Task force on chronic interstitial lung disease in immunocompetent children.
AB  - Chronic interstitial lung diseases in children represent a heterogeneous group of
      disorders of both known and unknown causes that share common histological
      features. Despite many efforts these diseases continue to present clinical
      management dilemmas, principally because of their rare frequency that limits
      considerably the possibilities of collecting enough cases for clinical and
      research studies. Through a Task Force conducted by the European Respiratory
      Society, which comprised respiratory physicians and basic scientists from across
      Europe, 185 cases of interstitial lung diseases in immunocompetent children were
      collected and reviewed. The present report provides important clinically-relevant
      information on the current approach to diagnosis and management of chronic
      interstitial lung diseases in children. In addition, recommendations for the
      management of paediatric interstitial lung diseases, as well as new insights into
      interstitial lung diseases pathophysiology during childhood are discussed.

PMID- 15459151
TI  - Occupational asthma in newly employed workers in intensive swine confinement
      facilities.
AB  - Respiratory symptoms, reductions in pulmonary function and increased bronchial
      responsiveness have been described in exposed workers and in naive volunteers
      exposed to intensive swine production facilities. Typically, this occurs in
      persons who have been employed for a long duration or in previously unexposed,
      naive volunteers. The current authors describe four cases, all female, who
      developed acute onset of wheezing and cough suggestive of asthma within weeks of
      commencing full-time employment in intensive swine production facilities. None of
      the workers were aware of any previous asthma, allergies or hay fever. All four
      employees reported improvement of symptoms on cessation of work in the facilities
      and consequent withdrawal from exposure. However, when seen at the respiratory
      clinic, cases 1 and 3 continued to be either mildly symptomatic or were taking
      medications with continued borderline airways responsiveness, as measured by
      methacholine challenge test up to 4 and 5 months, respectively, following work
      cessation. Case 2 continued to have symptoms for > or =3 months after work
      cessation. Only case 1, however, was seen at repeated visits in the respiratory
      clinic. One worker participated in a work re-entry trial and experienced profound
      coughing and chest tightness within an hour of entry, after which, the trial had
      to be terminated. Provocative concentration causing a 20% fall in forced
      expiratory volume in one second (PC20) measured 5 h later was lower than pre
      trial PC20. No acute exposure event was recorded in the workers prior to the
      onset of symptoms. To the current authors' knowledge, this is the first report of
      occupational asthma occurring in newly employed full-time intensive swine
      production workers after a short-term exposure and should raise awareness that
      previously unexposed workers may be at risk of developing what would appear to be
      long-term asthma after relatively short-term exposure.

PMID- 15459152
TI  - Intravenous iloprost bridging to orthotopic liver transplantation in
      portopulmonary hypertension.
AB  - Portopulmonary hypertension (PPHTN) is associated with poor prognosis and high
      perioperative mortality after orthotopic liver transplantation. This study
      documents the first case of a patient with PPHTN who was successfully bridged to
      orthotopic liver transplantation with i.v. iloprost, a stable prostacyclin
      analogue. The PPHTN had resolved completely 4 months after successful
      transplantation. In conclusion, portopulmonary hypertension is a relative
      contraindication to orthotopic liver transplantation, which should be attempted
      only if pulmonary haemodynamics improve with prostanoids. In this context,
      iloprost may be a valuable alternative to epoprostenol.

PMID- 15459153
TI  - Infliximab treatment in a patient with rheumatoid arthritis and pulmonary
      fibrosis.

PMID- 15459154
TI  - Nasal versus full face mask for noninvasive ventilation in chronic respiratory
      failure.

PMID- 15459155
TI  - Methacholine and macrolides.

PMID- 15459156
TI  - "Chronic obstructive pulmonary disease": the diagnostic last refuge of the
      intellectually challenged?

PMID- 15459157
TI  - Protective effect on AMP airway responsiveness after a single dose of
      fluticasone.

PMID- 15459160
TI  - Why should the poor insure? Theories of decision-making in the context of health
      insurance.
AB  - Increasingly, low- and middle-income countries are looking to community-based
      health insurance (CBHI) as a means of ensuring access to health care for the
      poor. However, little evidence exists about the determining factors that affect
      poor individuals' insurance decisions. This article reviews the economic and
      social literature on theories of decision-making, and presents empirical findings
      from different socio-economic contexts to describe individuals' insurance
      enrolment decisions in a low-income environment. Evidence from these studies
      suggests that several factors may explain poor households' decision to insure or
      remain uninsured. Combining empirical evidence with theories may serve to develop
      health policies to address issues related to the insurance design, the socio
      economic and the informational context; with the overall objective of improving
      access to care for the poor.

PMID- 15459161
TI  - The process of changing national malaria treatment policy: lessons from country
      level studies.
AB  - Widespread resistance of Plasmodium falciparum parasites to commonly used
      antimalarials, such as chloroquine, has resulted in many endemic countries
      considering changing their malaria treatment policy. Identifying and
      understanding the key influences that affect decision-making, and factors that
      facilitate or undermine policy implementation, is critical for improving the
      policy process and guiding resource allocation during this process. A historical
      review of archival documents from Malawi and data obtained from in-depth policy
      studies in four countries (Tanzania, South Africa, Kenya and Peru) that have
      changed malaria treatment policy provides important lessons about decision
      making, the policy cycle and complex policy environment, while specifically
      identifying strategies successfully employed to facilitate policy-making and
      implementation. Findings from these country-level studies indicate that the
      process of malaria drug policy review should be institutionalized in endemic
      countries and based on systematically collected data. Key stakeholders need to be
      identified early and engaged in the process, while improved communication is
      needed on all levels. Although malaria drug policy change is often perceived to
      be a daunting task, using these and other proven strategies should assist endemic
      countries to tackle this challenge in a systematic fashion that ensures the
      development and implementation of the rational malaria drug policy.

PMID- 15459162
TI  - Accountability and health systems: toward conceptual clarity and policy
      relevance.
AB  - Improved accountability is often called for as an element in improving health
      system performance. At first glance, the notion of better accountability seems
      straightforward, but it contains a high degree of complexity. If accountability
      is to be more than an empty buzzword, conceptual and analytical clarity is
      required. This article elaborates a definition of accountability in terms of
      answerability and sanctions, and distinguishes three types of accountability:
      financial, performance and political/democratic. An analytic framework for
      mapping accountability is proposed that identifies linkages among health sector
      actors and assesses capacity to demand and supply information and exercise
      oversight and sanctions. The article describes three accountability purposes:
      reducing abuse, assuring compliance with procedures and standards, and improving
      performance/learning. Using an accountability lens can: (1) help to generate a
      system-wide perspective on health sector reform, (2) identify connections among
      individual improvement interventions, and (3) reveal gaps requiring policy
      attention. These results can enhance system performance, improve service delivery
      and contribute to sound policymaking.

PMID- 15459163
TI  - The emergence of political priority for safe motherhood in Honduras.
AB  - Each year an estimated 500,000 to 600,000 women die due to complications from
      childbirth, making this one of the leading causes of death globally for women in
      their reproductive years. In 1987 a global initiative was launched to address the
      problem, but few developing countries since then have experienced a documented
      significant decline in maternal mortality levels. Honduras represents an
      exception. Between 1990 and 1997 the country's maternal mortality ratio--the
      number of deaths due to complications during pregnancy, childbirth and the
      postpartum period per 100,000 live births--declined 40% from 182 to 108, one of
      the largest reductions ever documented in such a short time span in the
      developing world. This paper draws on three political science literatures-
      constructivist international relations theory, policy transfer and agenda-setting
      -to explain how political priority for safe motherhood emerged in Honduras, a
      factor that underpinned the decline. Central to the explanation is the unusually
      cooperative relationship that developed between international donors and national
      health officials, resulting in effective transfer of policy and
      institutionalization of the cause within the domestic political system. The paper
      draws out implications of the case for understanding the political dynamics of
      health priority generation in developing countries.

PMID- 15459164
TI  - Knowledge and perceptions of drug quality among drug sellers and consumers in Lao
      PDR.
AB  - In most developing countries, including the Lao People's Democratic Republic
      (PDR), high prevalence of low quality drugs has been reported. The aim of this
      study was to explore knowledge and perceptions regarding drug quality among drug
      sellers and consumers, in Savannakhet province, Lao PDR. Quantitative and
      qualitative methods were used. Fifty-nine drug sellers and 278 exit customers
      were interviewed. Eight focus group discussions with drug sellers and community
      members were conducted. There was inadequate scientific drug knowledge among drug
      sellers. Only a few customers were aware of the existence of low quality drugs.
      Only one drug seller knew what constitutes a good quality drug according to the
      given criteria, and only two drug sellers knew the correct temperature for drug
      storage. Forty-four per cent had correct knowledge on drug labelling and 73%
      could read the expiry date. Fifty-eight per cent stated that they bought some
      drugs from unauthorized sources. Both drug sellers and consumers also elaborated
      on a local definition of drug quality. They determined drug quality by its
      perceived efficacy in the sense that a drug is good if it takes the disease away.
      They also trusted the responsible authorities not to provide them with low
      quality drugs. A majority of the consumers (73%) did not worry about the quality
      of the drugs, their greatest problem being financial constraints. People living
      in urban districts had significantly more knowledge on aspects of drug quality
      than those living in rural and remote areas. The limitations in scientific
      knowledge among drug sellers and the low awareness among consumers may contribute
      to the continued existence of low quality drugs. Government interventions through
      training of drug sellers and drug information for lay people are suggested.

PMID- 15459166
TI  - Abstracts of the joint meeting of the Society for Glycobiology and the Japanese
      Society for Carbohydrate Research, November 17-20, 2004, Honolulu, Hawaii, USA.

PMID- 15459165
TI  - Health care of female outpatients in south-central India: comparing public and
      private sector provision.
AB  - The object of this study was to compare components of quality of care provided to
      female outpatients by practitioners working in the private and public sectors in
      Karnataka State, India. Consultations conducted by 18 private practitioners and
      25 public-sector practitioners were observed for 5 days using a structured
      protocol. Private practitioners were selected from members of the Indian Medical
      Association in a predominantly rural sub-district of Kolar District. Government
      doctors were selected from a random sample of hospitals and health centres in
      three sub-districts of Mysore District. A total of 451 private-sector and 650
      public-sector consultations were observed; in each sector about half involved a
      female practitioner. The mean length of consultation was 2.81 minutes in the
      public sector and 6.68 minutes in the private sector. Compared with public-sector
      practitioners, private practitioners were significantly more likely to undertake
      a physical examination and to explain their diagnosis and prognosis to the
      patient. Privacy was much better in the private sector. One-third of public
      sector patients received an injection compared with two-thirds of private
      patients. The mean cost of drugs dispensed or prescribed were Rupees 37 and 74 in
      public and private sectors, respectively. Both in terms of thoroughness of
      diagnosis and doctor-patient communication, the quality of care appears to be
      much higher in the private than in the public sector. However, over-prescription
      of drugs by private practitioners may be occurring.

PMID- 15459167
TI  - Selecting distending medium for out-patient hysteroscopy. Does it really matter?
AB  - BACKGROUND: The aim of this prospective randomized study was to evaluate the role
      of carbon dioxide (CO2) and normal saline for diagnostic accuracy in out-patient
      hysteroscopy. METHODS: Women admitted to our Department in order to undergo total
      abdominal hysterectomy also underwent diagnostic hysteroscopy, 12-24 h prior to
      surgery. The selection of distending medium was made after randomization. Two
      groups of patients were formed, group A (CO2; n=39) and group B (normal saline;
      n=35). More than half of the women in the study population were post-menopausal.
      Post-hysteroscopy, all women were asked to rank any symptom that they felt during
      the procedure on a 4-point scale (0=none; 1=mild; 2=severe; 3=inability to
      perform hysteroscopy). The hysteroscopic diagnosis was compared with the
      macroscopic findings and the histological examination of the surgical specimen
      after hysterectomy. RESULTS: The percentage who completed hysteroscopy was 89.74%
      within group A and 97.14% within group B. Most patients of both groups felt some
      pain of mild intensity. The diagnostic accuracy of hysteroscopy was similar for
      both media when major pathology [large polyps (group A 91.7%; group B 92.7%),
      myomas (group A 81.25%; group B 92.7%) and/or hyperplasia (group A 87.5%; group B
      90.2%)] of the endometrial cavity was detected. In contrast, in cases of minor
      pathology (small polyps, mucosal elevations, crypts, hypervascularization),
      hysteroscopy with saline presented with significantly higher diagnostic accuracy
      (85.4%) compared with hysteroscopy with CO2 (64.6%). CONCLUSIONS: In out-patient
      hysteroscopy, CO2 and normal saline were comparable with regard to patient
      discomfort and for the detection of major pathology of the endometrial cavity.
      Normal saline seems to be the most appropriate medium for the detection of minor
      pathology of the endometrial cavity.

PMID- 15459168
TI  - Taskforce 8: ethics of medically assisted fertility treatment for HIV positive
      men and women.
AB  - In this 8th statement of the ESHRE Taskforce on Ethics and Law, the focus is on
      the ethical issues raised by (assisted) reproduction for HIV positive men and
      women. Due to treatment improvements, their life expectancy has increased
      substantially. This, in combination with the reduction of perinatal transmission
      to the child, makes the creation of a family more acceptable. Recommendations are
      made concerning methods of avoiding HIV transmission in the couple and to their
      offspring. It is concluded that, if certain precautions are taken, medical
      assistance to reproduction of HIV positive people is ethically acceptable. For
      the time being, only cases of serodiscordant couples should be considered.

PMID- 15459169
TI  - The place of the crossover design in infertility trials: a maximum likelihood
      approach.
AB  - BACKGROUND: For some years, there has been a debate as to the place of the
      crossover trial in assisted reproduction technology (ART). We aimed to
      investigate whether crossover and parallel designs result in different estimates
      of treatment effects. METHODS: We carried out computer simulation of cohorts of
      patients undergoing either intra-uterine insemination (IUI) or IVF under both
      parallel and crossover designs, under scenarios involving censoring and carryover
      effects. Results of the simulation were analysed using a maximum likelihood
      approach. RESULTS: No relevant difference was found between the designs. The
      crossover design resulted in slightly more pregnancies than the parallel design.
      Carryover effects may slightly distort the estimates of treatment effects.
      Crossover and parallel designs will produce essentially the same statistical
      estimates of treatment effect and percentage of pregnancies. The crossover design
      is an acceptable design in infertility research provided the data are analysed
      correctly.

PMID- 15459170
TI  - A novel 30 bp deletion in the FOXL2 gene in a phenotypically normal woman with
      primary amenorrhoea: case report.
AB  - In a Slovene patient with primary amenorrhoea without an association with
      blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), a novel 30 bp
      deletion was identified in the FOXL2 gene. We report the clinical features of
      this woman who has spontaneously conceived and delivered two live healthy babies.
      The novel deletion was predicted to remove 10 out of 14 alanines (A221_A230del),
      from the polyalanine tract downstream of the winged helix/forkhead domain of the
      FOXL2 protein. The patient's parents and sister were shown not to carry this
      deletion. Despite seeing an anovulatory secretory pattern of FSH, follicles
      developed spontaneously. Persistent and consistent monitoring have practical
      implications for genetic and fertility counselling in the era when women with
      premature ovarian failure usually seek ovum donation. The role of FOXL2 in the
      development of infertility is still unclear, but several lines of evidence
      suggest that it plays a central role in follicle development.

PMID- 15459171
TI  - Embryotrophic factor-3 from human oviductal cells enhances proliferation,
      suppresses apoptosis and stimulates the expression of the beta1 subunit of sodium
      potassium ATPase in mouse embryos.
AB  - BACKGROUND: Embrytrophic factor-3 (ETF-3) from human oviductal cells enhanced the
      development of mouse preimplantation embryos. This report studied the
      embryotrophic mechanisms of the molecule. METHODS AND RESULTS: Mouse embryos were
      incubated with ETF-3 for 24 h at different stages of development. ETF-3 treatment
      between 96 and 120 h post-HCG increased the cell count of blastocysts, whilst
      treatment between 72 and 96 h post-HCG enhanced the expansion and hatching of the
      blastocysts. ETF-3 increased the cell number of the embryos by suppressing
      apoptosis and increasing proliferation as determined by TUNEL and
      bromodeoxyuridine uptake assays, respectively. Real-time quantitative PCR showed
      that the in vivo developed and ETF-3-treated blastocysts had a significantly
      higher mRNA copy number of Na/K-ATPase-beta1, but not of hepsin, than that of
      blastocysts cultured in medium alone. The former gene was associated with
      cavitation of blastocysts while the latter was related to hatching of blastocyst.
      The beneficial effect of ETF-3 on blastocyst hatching was also seen when ETF-3
      supplemented commercially available sequential culture medium for human embryo
      culture was used to culture mouse embryos. CONCLUSIONS: ETF-3 improves embryo
      development by enhancing proliferation, suppressing apoptosis and stimulating
      expression of genes related to blastocyst cavitation. Supplementating human
      embryo culture medium with ETF-3 may improve the success rate in clinical
      assisted reproduction.

PMID- 15459172
TI  - Mutation analysis of two candidate genes for premature ovarian failure, DACH2 and
      POF1B.
AB  - BACKGROUND: Balanced X;autosome translocations interrupting the 'critical region'
      of the long arm of the human X chromosome are often associated with premature
      ovarian failure (POF). However, the mechanisms leading to X-linked ovarian
      dysfunction are largely unknown, as the majority of the X chromosome breakpoints
      have been mapped to gene-free genomic regions. A few genes have been found to be
      interrupted, but their role has never been clarified. METHODS AND RESULTS: By
      fine mapping of the X chromosome breakpoint of an X;autosome balanced
      translocation, we identified a new interrupted gene, POF1B. We performed a
      mutation analysis of POF1B and of another gene previously identified, DACH2,
      localized approximately 700 kb distal in Xq21, in a cohort of >200 Italian POF
      patients. Rare mutations were found in patients in both genes. CONCLUSIONS: Our
      findings could not demonstrate any involvement of POF1B, but suggest that rare
      mutations in the DACH2 gene may have a role in the POF phenotype.

PMID- 15459173
TI  - Are volunteers delivering semen samples in fertility studies a biased population?
AB  - BACKGROUND: It is not known to what extent the results of epidemiological studies
      on male fertility and semen quality based on voluntary participation in the
      general population are relevant. METHODS: In a study on the reproductive health
      of male partners of pregnant women, information was obtained from a group of men
      agreeing to collect a semen sample and to complete a questionnaire (group A), a
      group only completing the questionnaire (group B) and from men refusing to
      participate altogether (group C). RESULTS: The participation rate (group A) was
      15.8% for 1409 men approached. Ages and socio-professional status were similar in
      the three groups. Time to pregnancy (TTP) was not significantly different in
      groups A and B, although there appeared to be an insignificantly higher
      proportion of couples taking longer than 12 months to conceive in group A than in
      group B. A history of urogenital disease appeared to be more frequent in groups A
      and B than in the general population. However, comparable semen characteristics
      were found for men with or without a history of urogenital disease. Pregnancy
      outcomes were similar in the three groups. CONCLUSIONS: The present study does
      not suggest major selection bias, although the social and reproductive histories
      of these men may prompt them to participate. Such factors need to be accounted
      for in similar studies.

PMID- 15459174
TI  - Anti-Mullerian hormone plasma levels in spontaneous menstrual cycle and during
      treatment with FSH to induce ovulation.
AB  - BACKGROUND: Anti-Mullerian hormone (AMH) is member of the transforming growth
      factor-beta superfamily of growth factors. AMH is detected in serum from women of
      reproductive age and its levels vary slightly with the menstrual cycle, reaching
      the peak value in the late follicular phase. The present study was undertaken to
      assess the effect of controlled ovarian stimulation on AMH secretion by the ovary
      in healthy women in order to obtain more insight into the relationship between
      this peptide and gonadal steroids. METHODS: Twenty-four normally cycling women
      attending the infertility clinic volunteered for this study and AMH was measured
      in blood samples obtained during both spontaneous and FSH-treated cycles.
      RESULTS: AMH plasma levels did not change significantly from day 2 to day 6 in
      spontaneous cycles. On the contrary, AMH levels decreased progressively from day
      2 to day 6 in FSH-treated cycles. A significant positive correlation was found
      between the decrease in AMH and the increase in estradiol plasma levels in FSH
      treated cycles and between basal AMH and the peak estradiol (E2) during exogenous
      FSH administration. CONCLUSIONS: The present study demonstrated that AMH plasma
      levels did not change during the follicular phase of the menstrual cycle and that
      exogenous FSH administration is followed by a significant reduction in AMH levels
      which is probably secondary to the gonadotrophin effect on the process of
      follicular development.

PMID- 15459175
TI  - Reduced penetrance of craniofacial anomalies as a function of deletion size and
      genetic background in a chromosome engineered partial mouse model for Smith
      Magenis syndrome.
AB  - Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation
      syndrome associated with del(17)(p11.2p11.2). The phenotype is variable even in
      patients with deletions of the same size. RAI1 has been recently suggested as a
      major gene for majority of the SMS phenotypes, but its role in the full spectrum
      of the phenotype remains unclear. Df(11)17/+ mice contain a heterozygous deletion
      in the mouse region syntenic to the SMS common deletion, and exhibit craniofacial
      abnormalities, seizures and marked obesity, partially reproducing the SMS
      phenotype. To further study the genetic basis for the phenotype, we constructed
      three lines of mice with smaller deletions [Df(11)17-1, Df(11)17-2 and Df(11)17
      3] using retrovirus-mediated chromosome engineering to create nested deletions.
      Both craniofacial abnormalities and obesity have been observed, but the
      penetrance of the craniofacial phenotype was markedly reduced when compared with
      Df(11)17/+ mice. Overt seizures were not observed. Phenotypic variation has been
      observed in mice with the same deletion size in the same and in different genetic
      backgrounds, which may reflect the variation documented in the patients. These
      results indicate that the smaller deletions contain the gene(s), most likely
      Rai1, causing craniofacial abnormalities and obesity. However, genes or
      regulatory elements in the larger deletion, which are not located in the smaller
      deletions, as well as genes located elsewhere, also influence penetrance and
      expressivity of the phenotype. Our mouse models refined the genomic region
      important for a portion of the SMS phenotype and provided a basis for further
      molecular analysis of genes associated with SMS.

PMID- 15459176
TI  - Pituitary hypoplasia and respiratory distress syndrome in Prop1 knockout mice.
AB  - Mutations in Prophet of PIT1 (Prop1), one of several homeodomain transcription
      factors that are required for the development of the anterior pituitary gland,
      are the predominant cause of MPHD (multiple pituitary hormone deficiency) in
      humans. We show that deletion of Prop1 in mice causes severe pituitary hypoplasia
      with failure of the entire Pit1 lineage and delayed gonadotrope development. The
      pituitary hormone deficiencies cause secondary endocrine problems and a high rate
      of perinatal mortality due to respiratory distress. Lung atelectasis in mutants
      correlates with reduced levels of NKX2.1 and surfactant. Lethality of mice
      homozygous for either the null allele or a spontaneous hypomorphic allele is
      strongly influenced by genetic background. Prop1-null mice are an excellent model
      for MPHD and may be useful for testing the efficacy of pharmaceutical
      intervention for neonatal respiratory distress.

PMID- 15459177
TI  - A mouse model for Finnish variant late infantile neuronal ceroid lipofuscinosis,
      CLN5, reveals neuropathology associated with early aging.
AB  - Neuronal ceroid lipofuscinoses (NCL) comprise the most common group of childhood
      encephalopathies caused by mutations in eight genetic loci, CLN1-CLN8. Here, we
      have developed a novel mouse model for the human vLINCL (CLN5) by targeted
      deletion of exon 3 of the mouse Cln5 gene. The Cln5-/- mice showed loss of vision
      and accumulation of autofluorescent storage material in the central nervous
      system (CNS) and peripheral tissues without prominent brain atrophy. The
      ultrastructure of the storage material accurately replicated the abnormalities in
      human patients revealing mixture of lamellar profiles including fingerprint
      profiles as well as curvilinear and rectilinear bodies in electronmicroscopic
      analysis. Prominent loss of a subset of GABAergic interneurons in several brain
      areas was seen in the Cln5-/- mice. Transcript profiling of the brains of the
      Cln5-/- mice revealed altered expression in several genes involved in
      neurodegeneration, as well as in defense and immune response, typical of age
      associated changes in the CNS. Downregulation of structural components of myelin
      was detected and this agrees well with the hypomyelination seen in the human
      vLINCL patients. In general, the progressive pathology of the Cln5-/- brain
      mimics the symptoms of the corresponding neurodegenerative disorder in man. Since
      the Cln5-/- mice do not exhibit significant brain atrophy, these mice could serve
      as models for studies on molecular processes associated with advanced aging.

PMID- 15459178
TI  - Allelic expression imbalance of the human CYP3A4 gene and individual phenotypic
      status.
AB  - The human cytochrome P450 3A4 (CYP3A4) plays a dominant role in the metabolism of
      numerous clinically useful drugs. Alterations in the activity or expression of
      this enzyme may account for a major part of the variation in drug responsiveness
      and toxicity. However, it is generally accepted that most of the known single
      nucleotide polymorphisms in the coding and 5'-flanking regions are not the main
      determinants for the large inter-individual variability of CYP3A4 expression and
      activity. We show that the allelic variation is critically involved in
      determining the individual total hepatic CYP3A4 mRNA level and metabolic
      capability. There exists a definite correlation between the total CYP3A4 mRNA
      level and allelic expression ratio, the relative transcript level ratio derived
      from the two alleles. Individuals with a low expression ratio, exhibiting a large
      difference of transcript level between the two alleles, revealed extremely low
      levels of total hepatic CYP3A4 mRNA, and thus low metabolic capability as
      assessed by testosterone 6beta-hydroxylation. These results present a new insight
      into the individualized CYP3A4-dependent pharmacotherapy and the importance of
      expression imbalance to human phenotypic diversity.

PMID- 15459179
TI  - Evidence for genetic modifiers of postnatal lethality in PWS-IC deletion mice.
AB  - Prader-Willi syndrome (PWS), most notably characterized by infantile hypotonia,
      short stature and morbid obesity, results from deficiencies in multiple genes
      that are subject to genomic imprinting. The usefulness of current mouse models of
      PWS has been limited by postnatal lethality in affected mice. Here, we report the
      survival of the PWS-imprinting center (IC) deletion mice on a variety of strain
      backgrounds. Expression analyses of the genes affected in the PWS region suggest
      that while there is low-level expression from both parental alleles in PWS-IC
      deletion pups, this expression does not explain their survival on certain strain
      backgrounds. Rather, the data provide evidence for strain-specific modifier genes
      that support the survival of PWS-IC deletion mice.

PMID- 15459180
TI  - Disruption of a novel ectodermal neural cortex 1 antisense gene, ENC-1AS and
      identification of ENC-1 overexpression in hairy cell leukemia.
AB  - Karyotypical alteration of chromosome 5 and in particular band 5q13 is a frequent
      finding in hairy cell leukemia (HCL). We have previously identified a number of
      candidate genes localized in close proximity to a constitutional
      inv(5)(p13.1q13.3) breakpoint in one HCL patient. These included beta
      hexosaminodase HEXB, frequently mutated in the lysosomal storage disorder
      Sandhoff disease. We now report that the 5q13.3 breakpoint disrupts a novel
      evolutionary conserved alternative isoform of HEXB. This isoform directly
      overlaps, in a cis-antisense fashion, exon 1 of the gene for ectodermal neuronal
      cortex 1 ENC-1, and was thus named ENC-1AS. ENC-1 has previously been shown to be
      overexpressed in several malignancies, and is believed to play a critical
      regulatory role in malignant transformation of various tumors. Importantly,
      subsequent analysis of ENC-1 in purified primary HCL tumor cells revealed a
      striking upregulation of ENC-1 in all 26 patients examined, compared with normal
      peripheral blood lymphocytes from healthy donors. Upon further analysis of the
      ENC-1/ENC-1AS locus, we identified a complex 5' regulatory mechanism involving an
      inverse expression of the ENC-1 sense and the ENC-1AS transcripts in several
      tissues supporting the hypothesis that expression of ENC-1AS regulates ENC-1
      levels. In addition, we have also found tissue-specific methylation of a 1.2 kb
      segment encompassing the overlapping ENC-1/ENC-1AS 5' exons, adding to the
      complexity of the regulation of this locus. Altogether, these results suggest
      that upregulation of ENC-1 contributes to the development of HCL and provides new
      information on the possible dysregulation of ENC-1 including expression of a
      novel antisense gene, ENC-1AS.

PMID- 15459181
TI  - ATM is required for the cellular response to thymidine induced replication fork
      stress.
AB  - Genetically distinct checkpoints, activated as a consequence of either DNA
      replication arrest or ionizing radiation-induced DNA damage, integrate DNA repair
      responses into the cell cycle programme. The ataxia-telangiectasia mutated (ATM)
      protein kinase blocks cell cycle progression in response to DNA double strand
      breaks, whereas the related ATR is important in maintaining the integrity of the
      DNA replication apparatus. Here, we show that thymidine, which slows the
      progression of replication forks by depleting cellular pools of dCTP, induces a
      novel DNA damage response that, uniquely, depends on both ATM and ATR. Thymidine
      induces ATM-mediated phosphorylation of Chk2 and NBS1 and an ATM-independent
      phosphorylation of Chk1 and SMC1. AT cells exposed to thymidine showed decreased
      viability and failed to induce homologous recombination repair (HRR). Taken
      together, our results implicate ATM in the HRR-mediated rescue of replication
      forks impaired by thymidine treatment.

PMID- 15459182
TI  - Genome-wide demethylation destabilizes CTG.CAG trinucleotide repeats in mammalian
      cells.
AB  - Many neurological diseases, including myotonic dystrophy, Huntington's disease
      and several spinocerebellar ataxias, result from intergenerational increases in
      the length of a CTG.CAG repeat tract. Although the basis for intergenerational
      repeat expansion is unclear, repeat tracts are especially unstable during
      germline development and production of gametes. Mammalian development is
      characterized by waves of genome-wide demethylation and remethylation. To test
      whether changes in methylation status might contribute to trinucleotide repeat
      instability, we examined the effects of DNA methyltransferase inhibitors on
      trinucleotide repeat stability in mammalian cells. Using a selectable genetic
      system for detection of repeat contractions in CHO cells, we showed that the rate
      of contractions increased >1000-fold upon treatment with the DNA
      methyltransferase inhibitor 5-aza-deoxycytidine (5-aza-CdR). The link between DNA
      demethylation and repeat instability was strengthened by similar results obtained
      with hydralazine treatment, which inhibits expression of DNA methyltransferase.
      In human cells from myotonic dystrophy patients, treatment with 5-aza-CdR
      strongly destabilized repeat tracts in the DMPK gene, with a clear bias toward
      expansion. The bias toward expansion events and changes in repeat length that
      occur in jumps, rather than by accumulation of small changes, are reminiscent of
      the intergenerational repeat instability observed in human patients. The dramatic
      destabilizing effect of DNA methyltransferase inhibitors supports the hypothesis
      that changes in methylation patterns during epigenetic reprogramming may trigger
      the intergenerational repeat expansions that lead to disease.

PMID- 15459183
TI  - CD72 polymorphisms associated with alternative splicing modify susceptibility to
      human systemic lupus erythematosus through epistatic interaction with FCGR2B.
AB  - We previously reported association of FCGR2B-Ile232Thr with systemic lupus
      erythematosus (SLE) in three Asian populations. Because polymorphism of CD72,
      another inhibitory receptor of B cells, was associated with murine SLE, we
      identified human CD72 polymorphisms, tested their association with SLE and
      examined genetic interaction with FCGR2B in the Japanese (160 SLE, 277 controls),
      Thais (87 SLE, 187 controls) and Caucasians (94 families containing SLE members).
      Four polymorphisms and six rare variations were detected. The former constituted
      two major haplotypes that contained one or two repeats of 13 nucleotides in
      intron 8 (designated as *1 and *2, respectively). Although association with
      susceptibility to SLE was not detected, the *1 allele was significantly
      associated with nephritis among the Japanese patients (P=0.024). RT-PCR
      identified a novel alternatively spliced (AS) transcript that was expressed at
      the protein level in COS-7 transfectants. The ratio of AS/common isoforms was
      strikingly increased in individuals with *2/*2 genotype when compared with *1/*1
      (P=0.000038) or *1/*2 (P=0.0085) genotypes. Using the two Asian cohorts,
      significant association of FCGR2B-232Thr/Thr with SLE was observed only in the
      presence of CD72-*1/*1 genotype (OR 4.63, 95% CI 1.47-14.6, P=0.009 versus FCGR2B
      232Ile/Ile plus CD72-*2/*2). Minigene assays demonstrated that the 13-nucleotide
      repeat and 4 bp deletion within the same haplotype of intron 8 could regulate
      alternative splicing. The AS isoform lacks exon 8, and is deduced to contain 49
      amino acid changes in the membrane-distal portion of the extracellular domain,
      where considerable amino acid changes are known in CD72(c) allele associated with
      murine SLE. These results indicated that the presence of CD72-*2 allele decreases
      risk for human SLE conferred by FCGR2B-232Thr, possibly by increasing the AS
      isoform of CD72.

PMID- 15459184
TI  - NF-Y regulates the antisense promoter, bidirectional silencing, and differential
      epigenetic marks of the Kcnq1 imprinting control region.
AB  - Antisense transcription has been shown to be one of the hierarchies that control
      gene expression in eukaryotes. Recently, we have documented that the mouse Kcnq1
      imprinting control region (ICR) harbors bidirectional silencing property, and
      this feature is linked to an antisense RNA, Kcnq1ot1. In this investigation,
      using genomic footprinting, we have identified three NF-Y transcription factor
      binding sites appearing in a methylation-sensitive manner in the Kcnq1ot1
      promoter. By employing a dominant negative mutant to the NF-Y transcription
      factor, we have shown that the NF-Y transcription factor positively regulates
      antisense transcription. Selective mutation of the conserved nucleotides in the
      NF-Y binding sites resulted in the loss of antisense transcription. The loss of
      antisense transcription from the Kcnq1ot1 promoter coincides with an enrichment
      in the levels of deacetylation and methylation at the lysine 9 residue of histone
      H3 and DNA methylation at the CpG residues, implying a crucial role for the NF-Y
      transcription factor in organizing the parent of origin-specific chromatin
      conformation in the Kcnq1 ICR. Parallel to the loss of antisense transcription,
      the loss of silencing of the flanking reporter genes was observed, suggesting
      that NF-Y-mediated Kcnq1ot1 transcription is critical in the bidirectional
      silencing process of the Kcnq1 ICR. These data highlight the NF-Y transcription
      factor as a crucial regulator of antisense promoter-mediated bidirectional
      silencing and the parent of origin-specific epigenetic marks at the Kcnq1 ICR.
      More importantly, for the first time, we document that NF-Y is involved in
      maintaining the antisense promoter activity against strong silencing conditions.

PMID- 15459185
TI  - Identification and characterization of a novel cytoplasm protein ICF45 that is
      involved in cell cycle regulation.
AB  - A novel cytoplasm protein, interphase cytoplasm foci protein 45 kDa (ICF45), was
      identified by screening the cDNA expression library for HeLa cells with serum
      from an autoimmune patient. The complete cDNA sequence of ICF45 was determined to
      be 1.32 kb and to encode 298 amino acids with an apparent molecular mass of 45
      kDa. The ICF45 transcripts were detected in different tissues and were relatively
      rich in human liver and lung tissues but scarce in brain tissue.
      Immunofluorescence with anti-ICF45-specific antibodies demonstrated that ICF45 is
      strongly expressed in interphase and cannot be seen in mitosis. The subcellular
      localization of ICF45 and fusion proteins GFP-ICF45, ICF45-GFP, and HA-ICF45
      showed ICF45 centralized into 1-2 dots in the cytoplasm and always near the
      nuclear membrane. The staining foci of ICF45 appeared to be slightly larger than
      centrosomes and in some cases were found to colocalize with centrosomes. After
      effectively silencing the ICF45 by RNAi, the growth and proliferation of the
      cells were significantly inhibited, and p53 was detected to be up-regulated. The
      silencing of ICF45 also resulted in an appearance of polycentrosome and
      multinuclear cells, which finally went to apoptosis. Our results suggest that
      ICF45 is a highly conserved novel protein, which is expressed in a cell cycle
      dependent manner and seemed to be involved in cell cycle progression and cell
      proliferation.

PMID- 15459186
TI  - Genetic mapping of activity determinants within cellular prion proteins: N
      terminal modules in PrPC offset pro-apoptotic activity of the Doppel helix B/B'
      region.
AB  - The PrP-like Doppel (Dpl) protein causes apoptotic death of cerebellar neurons in
      transgenic mice, a process prevented by expression of the wild type (wt) cellular
      prion protein, PrP(C). Internally deleted forms of PrP(C) resembling Dpl such as
      PrPDelta32-121 produce a similar PrP(C)-sensitive pro-apoptotic phenotype in
      transgenic mice. Here we demonstrate that these phenotypic attributes of wt Dpl,
      wt PrP(C), and PrPDelta132-121 can be accurately recapitulated by transfected
      mouse cerebellar granule cell cultures. This system was then explored by
      mutagenesis of the co-expressed prion proteins to reveal functional determinants.
      By this means, neuroprotective activity of wt PrP(C) was shown to be nullified by
      a deletion of the N-terminal charged region implicated in endocytosis and
      retrograde axonal transport (PrPDelta23-28), by deletion of all five octarepeats
      (PrPDelta51-90), or by glycine replacement of four octarepeat histidine residues
      required for selective binding of copper ions (Prnp"H/G"). In the case of Dpl,
      overlapping deletions defined a requirement for the gene interval encoding
      helices B and B' (DplDelta101-125). These data suggest contributions of copper
      binding and neuronal trafficking to wt PrP(C) function in vivo and place
      constraints upon current hypotheses to explain Dpl/PrP(C) antagonism by
      competitive ligand binding. Further implementation of this assay should provide a
      fuller understanding of the attributes and subcellular localizations required for
      activity of these enigmatic proteins.

PMID- 15459187
TI  - ADP-ribosylation factor 1-independent protein sorting and export from the trans
      Golgi network.
AB  - Polarized epithelial cells efficiently sort newly synthesized apical and
      basolateral proteins into distinct transport carriers that emerge from the trans
      Golgi network (TGN), and this sorting is recapitulated in nonpolarized cells.
      While the targeting signals of basolaterally destined proteins are generally
      cytoplasmically disposed, apical sorting signals are not typically accessible to
      the cytosol, and the transport machinery required for segregation and export of
      apical cargo remains largely unknown. Here we investigated the molecular
      requirements for TGN export of the apical marker influenza hemagglutinin (HA) in
      HeLa cells using an in vitro reconstitution assay. HA was released from the TGN
      in intact membrane-bound compartments, and export was dependent on addition of an
      ATP-regenerating system and exogenous cytosol. HA release was inhibited by
      guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) as well as under conditions known
      to negatively regulate apical transport in vivo, including expression of the acid
      activated proton channel influenza M2. Interestingly, release of HA was
      unaffected by depletion of ADP-ribosylation factor 1, a small GTPase that has
      been implicated in the recruitment of all known adaptors and coat proteins to the
      Golgi complex. Furthermore, regulation of HA release by GTPgammaS or M2
      expression was unaffected by cytosolic depletion of ADP-ribosylation factor 1,
      suggesting that HA sorting remains functionally intact in the absence of the
      small GTPase. These data suggest that TGN sorting and export of influenza HA does
      not require classical adaptors involved in the formation of other classes of
      exocytic carriers and thus appears to proceed via a novel mechanism.

PMID- 15459188
TI  - Spermine synthesis is required for normal viability, growth, and fertility in the
      mouse.
AB  - Spermidine is essential for viability in eukaryotes but the importance of the
      longer polyamine spermine has not been established. Spermine is formed from
      spermidine by the action of spermine synthase, an aminopropyltransferase, whose
      gene (SpmS) is located on the X chromosome. Deletion of part of the X chromosome
      that include SpmS in Gy mice leads to a striking phenotype in affected males that
      includes altered phosphate metabolism and symptoms of hypophosphatemic rickets,
      circling behavior, hyperactivity, head shaking, inner ear abnormalities,
      deafness, sterility, a profound postnatal growth retardation, and a propensity to
      sudden death. It was not clear to what extent these alterations were due to the
      loss of spermine synthase activity, since this chromosomal deletion extends well
      beyond the SpmS gene and includes at least one other gene termed Phex. We have
      bred the Gy carrier female mice with transgenic mice (CAG/SpmS mice) that express
      spermine synthase from the ubiquitous CAG promoter. The resulting Gy-CAG/SpmS
      mice had extremely high levels of spermine synthase and contained spermine in all
      tissues examined. These mice had a normal life span and fertility and a normal
      growth rate except for a reduction in body weight due to a loss of bone mass that
      was consistent with the observation that the derangement in phosphate metabolism
      is due to the loss of the Phex gene and was not restored. These results show that
      spermine synthesis is needed for normal growth, viability, and fertility in male
      mice and that regulation of spermine synthase content is not required.

PMID- 15459189
TI  - HIV-1 Nef promotes survival of TF-1 macrophages by inducing Bcl-XL expression in
      an extracellular signal-regulated kinase-dependent manner.
AB  - The Nef protein of human immunodeficiency virus-1 (HIV-1) is essential for the
      progression from human and simian immunodeficiency virus infection to full-blown
      AIDS. Recent studies indicate that Nef generates anti-apoptotic signals in HIV
      infected T cells, suppressing cell death early in infection to allow productive
      viral replication. Previous work from our laboratory has shown that Nef also
      promotes proliferation of myeloid cells through a signal transducer and activator
      of transcription 3-dependent pathway. Here we demonstrate that Nef suppresses
      cell death induced by cytokine deprivation in the human macrophage precursor cell
      line, TF-1. Nef selectively induced up-regulation of Bcl-XL, an anti-apoptotic
      gene that is also regulated by granulocyte/macrophage-colony stimulating factor
      in this cell line. Activation of the extracellular signal-regulated kinase (Erk)
      mitogen-activated protein kinase pathway also correlated with the survival of TF
      1/Nef cells. Using the selective mitogen-activated protein kinase kinase
      inhibitor PD98059, we found that Nef-induced Erk signaling is essential for Bcl
      XL up-regulation and cell survival. In contrast, expression of Bcl-XL and TF-1
      survival was not affected by dominant-negative signal transducer and activator of
      transcription 3. These data suggest that Nef produces survival signals in myeloid
      cells through Erk-mediated Bcl-XL induction, a pathway distinct from Nef survival
      pathways recently reported in T lymphocytes.

PMID- 15459190
TI  - Acyl carrier protein is a cellular target for the antibacterial action of the
      pantothenamide class of pantothenate antimetabolites.
AB  - Pantothenate is the precursor of the essential cofactor coenzyme A (CoA).
      Pantothenate kinase (CoaA) catalyzes the first and regulatory step in the CoA
      biosynthetic pathway. The pantothenate analogs N-pentylpantothenamide and N
      heptylpantothenamide possess antibiotic activity against Escherichia coli. Both
      compounds are substrates for E. coli CoaA and competitively inhibit the
      phosphorylation of pantothenate. The phosphorylated pantothenamides are further
      converted to CoA analogs, which were previously predicted to act as inhibitors of
      CoA-dependent enzymes. Here we show that the mechanism for the toxicity of the
      pantothenamides is due to the inhibition of fatty acid biosynthesis through the
      formation and accumulation of the inactive acyl carrier protein (ACP), which was
      easily observed as a faster migrating protein using conformationally sensitive
      gel electrophoresis. E. coli treated with the pantothenamides lost the ability to
      incorporate [1-(14)C]acetate to its membrane lipids, indicative of the inhibition
      of fatty acid synthesis. Cellular CoA was maintained at the level sufficient for
      bacterial protein synthesis. Electrospray ionization time-of-flight mass
      spectrometry confirmed that the inactive ACP was the product of the transfer of
      the inactive phosphopantothenamide moiety of the CoA analog to apo-ACP, forming
      the ACP analog that lacks the sulfhydryl group for the attachment of acyl chains
      for fatty acid synthesis. Inactive ACP accumulated in pantothenamide-treated
      cells because of the active hydrolysis of regular ACP and the slow turnover of
      the inactive prosthetic group. Thus, the pantothenamides are pro-antibiotics that
      inhibit fatty acid synthesis and bacterial growth because of the covalent
      modification of ACP.

PMID- 15459191
TI  - cFLIPL inhibits tumor necrosis factor-related apoptosis-inducing ligand-mediated
      NF-kappaB activation at the death-inducing signaling complex in human
      keratinocytes.
AB  - Human keratinocytes undergo apoptosis following treatment with tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) via surface-expressed TRAIL
      receptors 1 and 2. In addition, TRAIL triggers nonapoptotic signaling pathways
      including activation of the transcription factor NF-kappaB, in particular when
      TRAIL-induced apoptosis is blocked. The intracellular protein cFLIP(L) interferes
      with TRAIL-induced apoptosis at the death-inducing signaling complex (DISC) in
      many cell types. To study the role of cFLIP(L) in TRAIL signaling, we established
      stable HaCaT keratinocyte cell lines expressing varying levels of cFLIP(L).
      Functional analysis revealed that relative cFLIP(L) levels correlated with
      apoptosis resistance to TRAIL. Surprisingly, cFLIP(L) specifically blocked TRAIL
      induced NF-kappaB activation and TRAIL-dependent induction of the proinflammatory
      target gene interleukin-8. Biochemical characterization of the signaling pathways
      involved showed that apoptosis signaling was inhibited at the DISC in cFLIP(L)
      overexpressing keratinocytes, although cFLIP(L) did not significantly impair
      enzymatic activity of the receptor complex. In contrast, recruitment and
      modification of receptor-interacting protein was blocked in cFLIP(L)
      overexpressing cells. Taken together, our data demonstrate that cFLIP(L) is not
      only a central antiapoptotic modulator of TRAIL-mediated apoptosis but also an
      inhibitor of TRAIL-induced NF-kappaB activation and subsequent proinflammatory
      target gene expression. Hence, cFLIP(L) modulation in keratinocytes may not only
      influence apoptosis sensitivity but may also lead to altered death receptor
      dependent skin inflammation.

PMID- 15459192
TI  - Cytoplasmic inositol hexakisphosphate production is sufficient for mediating the
      Gle1-mRNA export pathway.
AB  - Production of inositol hexakisphosphate (IP6) by Ipk1, the inositol-1,3,4,5,6
      pentakisphosphate 2-kinase, is required for Gle1-mediated mRNA export in
      Saccharomyces cerevisiae cells. To examine the network of interactions that
      require IP6 production, an analysis of fitness defects was conducted in mutants
      harboring both an ipk1 null allele and a mutant allele in genes encoding
      nucleoporins or transport factors. Enhanced lethality was observed with a
      specific subset of mutants, including nup42, nup116, nup159, dbp5, and gle2, all
      of which had been previously connected to Gle1 function. Complementation of the
      nup116Deltaipk1Delta and nup42Deltaipk1Delta double mutants did not require the
      Phe-Gly repeat domains in the respective nucleoporins, suggesting that IP6 was
      acting subsequent to heterogeneous nuclear ribonucleoprotein targeting to the
      nuclear pore complex. With Nup42 and Nup159 localized exclusively to the nuclear
      pore complex cytoplasmic side, we speculated that IP6 may regulate a cytoplasmic
      step in mRNA export. To test this prediction, the spatial requirements for the
      production of IP6 were investigated. Restriction of Ipk1 to the cytoplasm did not
      block IP6 production. Moreover, coincident sequestering of both Ipk1 and Mss4 (an
      enzyme required for phosphatidylinositol 4,5-bisphosphate production) to the
      cytoplasm also did not block IP6 production. Given that the kinase required for
      inositol 1,3,4,5,6-pentakisphosphate production (Ipk2) is localized in the
      nucleus, these results indicated that soluble inositides were diffusing between
      the nucleus and the cytoplasm. Additionally, the cytoplasmic production of IP6 by
      plasma membrane-anchored Ipk1 rescued a gle1-2 ipk1-4 synthetic lethal mutant.
      Thus, cytoplasmic IP6 production is sufficient for mediating the Gle1-mRNA export
      pathway.

PMID- 15459193
TI  - Single domain antibodies derived from dromedary lymph node and peripheral blood
      lymphocytes sensing conformational variants of prostate-specific antigen.
AB  - The importance of the lymphocyte source to generate hybridomas or to construct
      antibody gene libraries from which to identify potent monoclonal antibodies is
      understudied. However, the few comparative studies that exist seem to favor the
      lymph node tissue as a B-cell source. Here the peripheral blood and lymph node
      lymphocytes of a dromedary immunized with prostate-specific antigen (PSA) have
      been employed to clone two independent gene banks of the variable domains of
      heavy-chain antibodies (i.e. the VHHs). Several PSA-specific VHHs were retrieved
      after panning of these phage-displayed VHH libraries. Some of them were derived
      from the same B-cell lineage, possibly reflecting the restricted primary
      repertoire of heavy-chain antibodies. Other binders originated from different B
      cell lineages and apparently converged toward a striking homologous amino acid
      sequence motif in their CDR3. This illustrates the strong somatic hypermutation
      and stringent antigen-driven selection ongoing in these animals. Although the
      various antigen binders exhibit a broad range of kinetic rate constants for their
      interaction with the PSA, leading to equilibrium constants from 70 pM to 100 nM,
      no significant difference existed between the binders from the two B-cell
      sources. The VHHs of both libraries were categorized in three groups based on
      nonoverlapping epitopes. Some of these VHHs could inhibit and others could
      enhance the proteolytic activity of the antigen. Remarkably, VHHs seem to sense
      or induce conformational changes on different PSA isoforms, a feature that might
      be exploited to study the PSA conformational flexibility and to discriminate the
      stages of prostate cancer.

PMID- 15459194
TI  - The expression of lactate dehydrogenase is important for the cell cycle of
      Toxoplasma gondii.
AB  - In Toxoplasma gondii, lactate dehydrogenase is encoded by two independent and
      developmentally regulated genes LDH1 and LDH2. These genes and their products
      have been implicated in the control of a metabolic flux during parasite
      differentiation. To investigate the significance of LDH1 and LDH2 in this
      process, we generated stable transgenic parasite lines in which the expression of
      these two expressed isoforms of lactate dehydrogenase was knocked down in a stage
      specific manner. These LDH knockdown parasites exhibited variable growth rates in
      either the tachyzoite or the bradyzoite stage, as compared with the parental
      parasites. Their differentiation processes were impaired when the parasites were
      grown under in vitro conditions. In vivo studies in a murine model system
      revealed that tachyzoites of these parasite lines were unable to form significant
      numbers of tissue cysts and to establish a chronic infection. Most importantly,
      all mice that were initially infected with tachyzoites of either of the four LDH
      knockdown lines survived a subsequent challenge with tachyzoites of the parental
      parasites (10(4)), a dose that usually causes 100% mortality, suggesting that
      live vaccination of mice with the LDH knockdown tachyzoites can confer protection
      against T. gondii. Thus, we conclude that LDH expression is essential for
      parasite differentiation. The knockdown of LDH1 and LDH2 expression gave rise to
      virulence-attenuated parasites that were unable to exhibit a significant brain
      cyst burden in a murine model of chronic infection.

PMID- 15459195
TI  - Fzo1, a protein involved in mitochondrial fusion, inhibits apoptosis.
AB  - Mitochondrial morphology and physiology are regulated by the processes of fusion
      and fission. Some forms of apoptosis are reported to be associated with
      mitochondrial fragmentation. We showed that overexpression of Fzo1A/B (rat)
      proteins involved in mitochondrial fusion, or silencing of Dnm1 (rat)/Drp1
      (human) (a mitochondrial fission protein), increased elongated mitochondria in
      healthy cells. After apoptotic stimulation, these interventions inhibited
      mitochondrial fragmentation and cell death, suggesting that a process involved in
      mitochondrial fusion/fission might play a role in the regulation of apoptosis.
      Consistently, silencing of Fzo1A/B or Mfn1/2 (a human homolog of Fzo1A/B) led to
      an increase of shorter mitochondria and enhanced apoptotic death. Overexpression
      of Fzo1 inhibited cytochrome c release and activation of Bax/Bak, as assessed
      from conformational changes and oligomerization. Silencing of Mfn or Drp1 caused
      an increase or decrease of mitochondrial sensitivity to apoptotic stimulation,
      respectively. These results indicate that some of the proteins involved in
      mitochondrial fusion/fission modulate apoptotic cell death at the mitochondrial
      level.

PMID- 15459197
TI  - Studies of the interaction of substituted mutants of BAX with yeast mitochondria
      reveal that the C-terminal hydrophobic alpha-helix is a second ART sequence and
      plays a role in the interaction with anti-apoptotic BCL-xL.
AB  - The role of the two ends of the pro-apoptotic protein BAX in its interaction with
      mitochondria was challenged by assaying substituted mutants in yeast cells for
      the ability to bind and insert into the mitochondrial membrane and to promote the
      release of cytochrome c. Mutations at the N-terminal end confirmed the inhibitory
      function of this zone, known as apoptotic regulation of targeting (ART). On the
      other hand, mutations at the C-terminal end of the protein support the hypothesis
      that the hydrophobic helix alpha9 is not required for the insertion of BAX. In
      addition, three mutations (a T174D single substitution in the helix alpha9, a
      K189E/K190E double substitution at the end of the protein, and a P168A mutation
      in the loop before alpha9) exhibited a strong binding capacity, a strong
      insertion, as well as high ability to induce cytochrome c release. Considering
      the positions of these mutations and their potential effect on the movement of
      helix alpha9, we propose that the C-terminal end of the protein behaves like a
      second ART. Also, opposite to a mutation that changes the conformation of the N
      terminal ART, the mutations in the C-terminal part of the protein impaired the
      inhibitory effect of anti-apoptotic BCL-xL over BAX insertion, suggesting that
      the conformation of the alpha9-helix plays a significant role in BAX/BCL-xL
      interaction.

PMID- 15459196
TI  - A naturally occurring mutation of the opsin gene (T4R) in dogs affects
      glycosylation and stability of the G protein-coupled receptor.
AB  - Rho (rhodopsin; opsin plus 11-cis-retinal) is a prototypical G protein-coupled
      receptor responsible for the capture of a photon in retinal photoreceptor cells.
      A large number of mutations in the opsin gene associated with autosomal dominant
      retinitis pigmentosa have been identified. The naturally occurring T4R opsin
      mutation in the English mastiff dog leads to a progressive retinal degeneration
      that closely resembles human retinitis pigmentosa caused by the T4K mutation in
      the opsin gene. Using genetic approaches and biochemical assays, we explored the
      properties of the T4R mutant protein. Employing immunoaffinity-purified Rho from
      affected RHO(T4R/T4R) dog retina, we found that the mutation abolished
      glycosylation at Asn(2), whereas glycosylation at Asn(15) was unaffected, and the
      mutant opsin localized normally to the rod outer segments. Moreover, we found
      that T4R Rho(*) lost its chromophore faster as measured by the decay of meta
      rhodopsin II and that it was less resistant to heat denaturation. Detergent
      solubilized T4R opsin regenerated poorly and interacted abnormally with the G
      protein transducin (G(t)). Structurally, the mutation affected mainly the "plug"
      at the intradiscal (extracellular) side of Rho, which is possibly responsible for
      protecting the chromophore from the access of bulk water. The T4R mutation may
      represent a novel molecular mechanism of degeneration where the unliganded form
      of the mutant opsin exerts a detrimental effect by losing its structural
      integrity.

PMID- 15459198
TI  - Binding of low density lipoprotein to platelet apolipoprotein E receptor 2'
      results in phosphorylation of p38MAPK.
AB  - Binding of low density lipoprotein (LDL) to platelets enhances platelet
      responsiveness to various aggregation-inducing agents. However, the identity of
      the platelet surface receptor for LDL is unknown. We have previously reported
      that binding of the LDL component apolipoprotein B100 to platelets induces rapid
      phosphorylation of p38 mitogen-activated protein kinase (p38MAPK). Here, we show
      that LDL-dependent activation of this kinase is inhibited by receptor-associated
      protein (RAP), an inhibitor of members of the LDL receptor family. Confocal
      microscopy revealed a high degree of co-localization of LDL and a splice variant
      of the LDL receptor family member apolipoprotein E receptor-2 (apoER2') at the
      platelet surface, suggesting that apoER2' may contribute to LDL-induced platelet
      signaling. Indeed, LDL was unable to induce p38MAPK activation in platelets of
      apoER2-deficient mice. Furthermore, LDL bound efficiently to soluble apoER2', and
      the transient LDL-induced activation of p38MAPK was mimicked by an anti-apoER2
      antibody. Association of LDL to platelets resulted in tyrosine phosphorylation of
      apoER2', a process that was inhibited in the presence of PP1, an inhibitor of Src
      like tyrosine kinases. Moreover, phosphorylated but not native apoER2' co
      precipitated with the Src family member Fgr. This suggests that exposure of
      platelets to LDL induces association of apoER2' to Fgr, a kinase that is able to
      activate p38MAPK. In conclusion, our data indicate that apoER2' contributes to
      LDL-dependent sensitization of platelets.

PMID- 15459199
TI  - Na+-dependent K+ uptake Ktr system from the cyanobacterium Synechocystis sp. PCC
      6803 and its role in the early phases of cell adaptation to hyperosmotic shock.
AB  - Transmembrane ion transport processes play a key role in the adaptation of cells
      to hyperosmotic conditions. Previous work has shown that the disruption of a
      ktrB/ntpJ-like putative Na(+)/K(+) transporter gene in the cyanobacterium
      Synechocystis sp. PCC 6803 confers increased Na(+) sensitivity, and inhibits
      HCO(3)(-) uptake. Here, we report on the mechanistic basis of this effect.
      Heterologous expression experiments in Escherichia coli show that three
      Synechocystis genes are required for K(+) transport activity. They encode an
      NAD(+)-binding peripheral membrane protein (ktrA; sll0493), an integral membrane
      protein, belonging to a superfamily of K(+) transporters (ktrB; formerly ntpJ;
      slr1509), and a novel type of ktr gene product, not previously found in Ktr
      systems (ktrE; slr1508). In E. coli, Synechocystis KtrABE-mediated K(+) uptake
      occurred with a moderately high affinity (K(m) of about 60 microm), and depended
      on both Na(+) and a high membrane potential, but not on ATP. KtrABE neither
      mediated Na(+) uptake nor Na(+) efflux. In Synechocystis sp. PCC 6803, KtrB
      mediated K(+) uptake required Na(+) and was inhibited by protonophore. A Delta
      ktrB strain was sensitive to long term hyperosmotic stress elicited by either
      NaCl or sorbitol. Hyperosmotic shock led initially to loss of net K(+) from the
      cells. The Delta ktrB cells shocked with sorbitol failed to reaccumulate K(+) up
      to its original level. These data indicate that in strain PCC 6803 K(+) uptake
      via KtrABE plays a crucial role in the early phase of cell turgor regulation
      after hyperosmotic shock.

PMID- 15459200
TI  - Inhibition of MAPK signaling pathways by VopA from Vibrio parahaemolyticus.
AB  - During infection, bacterial pathogens utilize a type III secretion system to
      inject effectors into the cytoplasm of a target cell where they disrupt the
      defense system of the host cell. Vibrio parahaemolyticus, a causative agent of
      gastroenteritis endemic in Southeast Asia, has a type III secretion system that
      encodes a novel member of the YopJ-like protein effector family, VopA (Vibrio
      outer protein A). Our studies revealed that Vibrio VopA encodes an evolutionarily
      conserved activity that is extremely potent and requires an intact catalytic site
      to abrogate signaling pathways in a manner distinct from that of other YopJ-like
      effectors. We observed that VopA efficiently inhibits the MAPK signaling pathways
      but not the NFkappaB pathway in mammalian cells. When expressed in yeast, VopA
      induces a growth arrest phenotype and also blocks yeast MAPK signaling pathways.
      Our observations provide insight into the immense diversity of targets utilized
      by YopJ-like effectors to manipulate eukaryotic signaling machineries that are
      important for the response and survival of the host cell during infection and/or
      symbiosis.

PMID- 15459201
TI  - Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720.
AB  - Sphingosine-1-phosphate (S1P), a lipid signaling molecule that regulates many
      cellular functions, is synthesized from sphingosine and ATP by the action of
      sphingosine kinase. Two such kinases have been identified, SPHK1 and SPHK2. To
      begin to investigate the physiological functions of sphingosine kinase and S1P
      signaling, we generated mice deficient in SPHK1. Sphk1 null mice were viable,
      fertile, and without any obvious abnormalities. Total SPHK activity in most Sphk1
      /-tissues was substantially, but not completely, reduced indicating the presence
      of multiple sphingosine kinases. S1P levels in most tissues from the Sphk1-/-
      mice were not markedly decreased. In serum, however, there was a significant
      decrease in the S1P level. Although S1P signaling regulates lymphocyte
      trafficking, lymphocyte distribution was unaffected in lymphoid organs of Sphk1-/
      mice. The immunosuppressant FTY720 was phosphorylated and elicited lymphopenia
      in the Sphk1 null mice showing that SPHK1 is not required for the functional
      activation of this sphingosine analogue prodrug. The results with these Sphk1
      null mice reveal that some key physiologic processes that require S1P receptor
      signaling, such as vascular development and proper lymphocyte distribution, can
      occur in the absence of SPHK1.

PMID- 15459202
TI  - Analysis of the secondary structure of beta-amyloid (Abeta42) fibrils by
      systematic proline replacement.
AB  - Amyloid fibrils in Alzheimer's disease mainly consist of 40- and 42-mer beta
      amyloid peptides (Abeta40 and Abeta42) that exhibit aggregative ability and
      neurotoxicity. Although the aggregates of Abeta peptides are rich in
      intermolecular beta-sheet, the precise secondary structure of Abeta in the
      aggregates remains unclear. To identify the amino acid residues involved in the
      beta-sheet formation, 34 proline-substituted mutants of Abeta42 were synthesized
      and their aggregative ability and neurotoxicity on PC12 cells were examined.
      Prolines are rarely present in beta-sheet, whereas they are easily accommodated
      in beta-turn as a Pro-X corner. Among the mutants at positions 15-32, only E22P
      Abeta42 extensively aggregated with stronger neurotoxicity than wild-type
      Abeta42, suggesting that the residues at positions 15-21 and 24-32 are involved
      in the beta-sheet and that the turn at positions 22 and 23 plays a crucial role
      in the aggregation and neurotoxicity of Abeta42. The C-terminal proline mutants
      (A42P-, I41P-, and V40P-Abeta42) hardly aggregated with extremely weak
      cytotoxicity, whereas the C-terminal threonine mutants (A42T- and I41T-Abeta42)
      aggregated potently with significant cytotoxicity. These results indicate that
      the hydrophobicity of the C-terminal two residues of Abeta42 is not related to
      its aggregative ability and neurotoxicity, rather the C-terminal three residues
      adopt the beta-sheet. These results demonstrate well the large difference in
      aggregative ability and neurotoxicity between Abeta42 and Abeta40. In contrast,
      the proline mutants at the N-terminal 13 residues showed potent aggregative
      ability and neurotoxicity similar to those of wild-type Abeta42. The
      identification of the beta-sheet region of Abeta42 is a basis for designing new
      aggregation inhibitors of Abeta peptides.

PMID- 15459203
TI  - Biochemical evidence for the presence of a single CD3delta and CD3gamma chain in
      the surface T cell receptor/CD3 complex.
AB  - The T cell antigen receptor (TCR) consists of an alphabeta heterodimer and
      associated invariant CD3gamma, delta, epsilon, and zeta chains (TCR/CD3 complex).
      The general stoichiometry of the receptor complex, which is believed to be one
      molecule each of TCRalpha, TCRbeta, CD3gamma, and CD3delta and two molecules each
      of CD3epsilon and CD3zeta, is not clearly understood. Although it has been shown
      that there are two chains of CD3epsilon and CD3zeta, the stoichiometry of
      CD3gamma or CD3delta chains in the surface antigen receptor complex has not been
      determined. In the present study, transgenic mice expressing an altered form of
      mouse CD3delta and CD3gamma were employed to show that the surface TCR complexes
      contain one molecule each of CD3delta and CD3gamma. Thymocytes from wild type and
      CD3 chain transgenic mice on the appropriate knockout background were surface
      biotinylated and immunoprecipitated using a specific antibody. The
      immunoprecipitates were resolved in two dimensions under nonreducing/reducing
      conditions to determine the stoichiometry of CD3delta and CD3gamma in the surface
      antigen receptor complex. Our data clearly show the presence of one molecule each
      of CD3delta and CD3gamma in the surface TCR/CD3 complex.

PMID- 15459204
TI  - Crucial role for nuclear factor of activated T cells in T cell receptor-mediated
      regulation of human interleukin-17.
AB  - The biological activities of the inflammatory cytokine interleukin (IL)-17 have
      been widely studied. However, comparatively little is known about how IL-17
      expression is controlled. Here, we examined the basis for transcriptional
      regulation of the human IL-17 gene. IL-17 secretion was induced in peripheral
      blood mononuclear cells following anti-CD3 cross-linking to activate the T cell
      receptor (TCR), and costimulatory signaling through CD28 strongly enhanced CD3
      induced IL-17 production. To define cis-acting elements important for IL-17 gene
      regulation, we cloned 1.25 kb of genomic sequence upstream of the transcriptional
      start site. This putative promoter was active in Jurkat T cells following CD3 and
      CD28 cross-linking, and its activity was inhibited by cyclosporin A and MAPK
      inhibitors. The promoter was also active in Hut102 T cells, which we have shown
      to secrete IL-17 constitutively. Overexpression of nuclear factor of activated T
      cells (NFAT) or Ras enhanced IL-17 promoter activity, and studies in Jurkat lines
      deficient in specific TCR signaling pathways provided supporting evidence for a
      role for NFAT. To delineate the IL-17 minimal promoter, we created a series of 5'
      truncations and identified a region between -232 and -159 that was sufficient for
      inducible promoter activity. Interestingly, two NFAT sites were located within
      this region, which bound to NFATc1 and NFATc2 in nuclear extracts from Hut102 and
      Jurkat cells. Moreover, mutations of these sites dramatically reduced both
      specific DNA binding and reporter gene activity, and chromatin
      immunoprecipitation assays showed occupancy of NFAT at this region in vivo.
      Together, these data show that NFAT is the crucial sensor of TCR signaling in the
      IL-17 promoter.

PMID- 15459205
TI  - Inhibition of Akt kinase activity by a peptide spanning the betaA strand of the
      proto-oncogene TCL1.
AB  - Akt plays a central role in the regulation of cellular anti-apoptosis underlying
      various human neoplastic diseases. We have demonstrated previously that TCL1 (a
      proto-oncogene underlying human T cell prolymphocytic leukemia) interacts with
      Akt and functions as an Akt kinase co-activator. With the aim to develop an Akt
      kinase inhibitor, we hypothesized that a peptide, which spans the Akt-binding
      site, binds to Akt and modulates Akt kinase activity and its downstream
      biological responses. Indeed, we demonstrated that a peptide, named "Akt-in" (Akt
      inhibitor, NH(2)-AVTDHPDRLWAWEKF-COOH, encompassing the betaA strand of human
      TCL1), interacted with Akt and specifically inhibited its kinase activity.
      Nuclear magnetic resonance studies suggested that interaction of Akt-in with the
      pleckstrin homology domain (PH) of Akt caused conformational changes on the
      variable loop 1 of Akt, the locus mediating phosphoinositide binding.
      Consistently, interaction of Akt-in with the Akt PH domain prevented
      phosphoinositide binding and hence inhibited membrane translocation and
      activation of Akt. Moreover, Akt-in inhibited not only cellular proliferation and
      anti-apoptosis in vitro but also in vivo tumor growth without any adverse effect.
      The roles of Akt, which possesses a PH domain, in intracellular signaling were
      well established. Hence, Akt inhibitors create an attractive target for
      anticancer therapy. However, no effective inhibitors specific for Akt have been
      developed. Akt-in, which inhibits association of phosphatidylinositol with Akt,
      is the first molecule to demonstrate specific Akt kinase inhibition potency. This
      observation will facilitate the design of specific inhibitors for Akt, a core
      intracellular survival factor underlying various human neoplastic diseases.

PMID- 15459206
TI  - Identification and characterization of functionally important elements in the
      multidrug resistance protein 1 COOH-terminal region.
AB  - The ATP binding cassette (ABC) transporter, multidrug resistance protein 1
      (MRP1/ABCC1), transports a broad spectrum of conjugated and unconjugated
      compounds, including natural product chemotherapeutic agents. In this study, we
      have investigated the importance of the COOH-terminal region of MRP1 for
      transport activity and basolateral plasma membrane trafficking. The COOH-terminal
      regions of some ABCC proteins have been implicated in protein trafficking, but
      the function of this region of MRP1 has not been defined. In contrast to results
      obtained with other ABCC proteins, we found that the COOH-proximal 30 amino acids
      of MRP1 can be removed without affecting trafficking to basolateral membranes.
      However, the truncated protein is inactive. Furthermore, removal of as few as 4
      COOH-terminal amino acids profoundly decreases transport activity. Although amino
      acid sequence conservation of the COOH-terminal regions of ABC proteins is low,
      secondary structure predictions indicate that they consist of a broadly conserved
      helix-sheet-sheet-helix-helix structure. Consistent with a conservation of
      secondary and tertiary structure, MRP1 hybrids containing the COOH-terminal
      regions of either the homologous MRP2 or the distantly related P-glycoprotein
      were fully active and trafficked normally. Using mutated proteins, we have
      identified structural elements containing five conserved hydrophobic amino acids
      that are required for activity. We show that these are important for binding and
      hydrolysis of ATP by nucleotide binding domain 2. Based on crystal structures of
      several ABC proteins, we suggest that the conserved amino acids may stabilize a
      helical bundle formed by the COOH-terminal three helices and may contribute to
      interactions between the COOH-terminal region and the protein's two nucleotide
      binding domains.

PMID- 15459207
TI  - ERK1/2 regulates intracellular ATP levels through alpha-enolase expression in
      cardiomyocytes exposed to ischemic hypoxia and reoxygenation.
AB  - Extracellular signal-regulated kinase 1/2 (ERK1/2) is known to function in cell
      survival in response to various stresses; however, the mechanism of cell survival
      by ERK1/2 remains poorly elucidated in ischemic heart. Here we applied functional
      proteomics by two-dimensional electrophoresis to identify a cellular target of
      ERK1/2 in response to ischemic hypoxia. Approximately 1500 spots were detected by
      Coomassie Brilliant Blue staining of a sample from unstimulated cells. The
      staining intensities of at least 50 spots increased at 6-h reoxygenation after 2
      h ischemic hypoxia. Of the 50 spots that increased, at least 4 spots were
      inhibited in the presence of PD98059, a MEK inhibitor. A protein with a molecular
      mass of 52 kDa that is strongly induced by ERK1/2 activation in response to
      ischemic hypoxia and reoxygenation was identified as alpha-enolase, a rate
      limiting enzyme in the glycolytic pathway, by liquid chromatography-mass
      spectrometry and amino acid sequencing. The expressions of the alpha-enolase mRNA
      and protein are inhibited during reoxygenation after ischemic hypoxia in the
      cells containing a dominant negative mutant of MEK1 and treated with a MEK
      inhibitor, PD98059, leading to a decrease in ATP levels. alpha-Enolase expression
      is also observed in rat heart subjected to ischemia-reperfusion. The induction of
      alpha-enolase by ERK1/2 appears to be mediated by c-Myc. The introduction of the
      alpha-enolase protein into the cells restores ATP levels and prevents cell death
      during ischemic hypoxia and reoxygenation in these cells. These results show that
      alpha-enolase expression by ERK1/2 participates in the production of ATP during
      reoxygenation after ischemic hypoxia, and a decrease in ATP induces apoptotic
      cell death. Furthermore, alpha-enolase improves the contractility of
      cardiomyocytes impaired by ischemic hypoxia. Our results reveal that ERK1/2 plays
      a role in the contractility of cardiomyocytes and cell survival through alpha
      enolase expression during ischemic hypoxia and reoxygenation.

PMID- 15459208
TI  - Inhibition of gap junction activity through the release of the C1B domain of
      protein kinase Cgamma (PKCgamma) from 14-3-3: identification of PKCgamma-binding
      sites.
AB  - We have shown previously that insulin-like growth factor-I or lens epithelium
      derived growth factor increases the translocation of protein kinase Cgamma
      (PKCgamma)to the membrane and the phosphorylation of Cx43 by PKCgamma and causes
      a subsequent decrease of gap junction activity (Nguyen, T. A., Boyle, D. L.,
      Wagner, L. M., Shinohara, T., and Takemoto, D. J. (2003) Exp. Eye Res. 76, 565
      572; Lin, D., Boyle, D. L., and Takemoto, D. J. (2003) Investig. Ophthalmol. Vis.
      Sci. 44, 1160-1168). Gap junction activity in lens epithelial cells is regulated
      by PKCgamma-mediated phosphorylation of Cx43. PKCgamma activity is stimulated by
      growth factor-regulated increases in the synthesis of diacylglycerol but is
      inhibited by cytosolic docking proteins such as 14-3-3. Here we have identified
      two sites on the PKCgamma-C1B domain that are responsible for its interaction
      with 14-3-3epsilon. Two sites, C1B1 (residues 101-112) and C1B5 (residues 141
      151), are located within the C1 domain of PKCgamma. C1B1 and/or C1B5 synthetic
      peptides can directly compete for the binding of 14-3-3epsilon, resulting in the
      release of endogenous cellular PKCgamma from 14-3-3epsilon, in vivo or in vitro,
      in activation of PKCgamma enzyme activity, phosphorylation of PKCgamma, in the
      subsequent translocation of PKCgamma to the membrane, and in inhibition of gap
      junction activity. Gap junction activity was decreased by at least 5-fold in
      cells treated with C1B1 or C1B5 peptides when compared with a control. 100 microM
      of C1B1 or C1B5 peptides also caused a 10- or 4-fold decrease of Cx43 plaque
      formation compared with control cells. The uptake of these synthetic peptides
      into cells was verified by using high pressure liquid chromatography and matrix
      assisted laser desorption ionization time-of-flight-mass spectrometry. We have
      demonstrated that the activity and localization of PKCgamma are regulated by its
      binding to 14-3-3epsilon at the C1B domain of PKCgamma. Synthetic peptides
      corresponding to these regions of PKCgamma successfully competed for the binding
      of 14-3-3epsilon to endogenous PKCgamma, resulting in inhibition of gap junction
      activity. This demonstrates that synthetic peptides can be used to exogenously
      regulate gap junctions.

PMID- 15459209
TI  - Is baseline quality of life useful for predicting survival with hormone
      refractory prostate cancer? A pooled analysis of three studies of the European
      Organisation for Research and Treatment of Cancer Genitourinary Group.
AB  - PURPOSE: Patients with symptomatic metastatic hormone-resistant prostate cancer
      (HRPC) survive a median of 10 months and are often regarded as a homogeneous
      group. Few prognostic factors have been identified so far. We examined whether
      baseline health-related quality of life (HRQOL) parameters assessed by the
      European Organisation for Research and Treatment of Cancer Quality of Life
      Questionnaire C30 (EORTC QLQ-C30) were independent prognostic factors of survival
      and whether they bring extra precision to the predictions achievable with models
      based on clinical and biochemical factors only. PATIENTS AND METHODS: Data of 391
      symptomatic (bone) metastatic HRPC patients from three randomized EORTC trials
      were used in multivariate Cox proportional hazards models. The significance level
      was set at alpha =.05. RESULTS: Of the 391 patients, 371 died, most of prostate
      cancer. Bone scan result, performance status, hemoglobin level, and insomnia and
      appetite loss as measured by the EORTC QLQ-C30 were independent predictors of
      survival. This model's area under the receiver operating curve was 0.65 compared
      with 0.63 without the two HRQOL factors. CONCLUSION: Certain HRQOL sores, at
      baseline, seem to be predictors for duration of survival in HRPC. However, such
      measurements do not add to the predictive ability of models based only on
      clinical and biochemical factors.

PMID- 15459211
TI  - Phase III trial of doxorubicin with or without cisplatin in advanced endometrial
      carcinoma: a gynecologic oncology group study.
AB  - PURPOSE: Doxorubicin and cisplatin have activity in endometrial carcinoma and at
      initiation of this study ranked as the most active agents. This trial of stage
      III, IV, or recurrent disease evaluated whether combining these agents increases
      response rate (RR) and prolongs progression-free survival (PFS) and overall
      survival (OS) over doxorubicin alone. PATIENTS AND METHODS: Of 299 patients
      registered, 281 (94%) were eligible. Regimens were doxorubicin 60 mg/m(2)
      intravenously or doxorubicin 60 mg/m(2) plus cisplatin 50 mg/m(2) every 3 weeks
      until disease progression, unacceptable toxicity, or a total of 500 mg/m(2)
      doxorubicin. RESULTS: There were 12 (8%) complete (CR) and 26 (17%) partial
      responses (PR) among 150 patients receiving doxorubicin versus 25 (19%) CRs and
      30 (23%) PRs among patients receiving the combination. The overall response rate
      was higher among patients receiving the combination (42%) compared with patients
      receiving doxorubicin (25%; P =.004). Median PFS was 5.7 and 3.8 months,
      respectively, for the combination and single agent. The PFS hazard ratio was
      0.736 (95% CI, 0.577 to 0.939; P =.014). Median OS was 9.0 and 9.2 months,
      respectively, for the combination and single agent. Overall death rates were
      similar in the two groups (hazard ratio, 0.928; 95% CI, 0.727 to 1.185). Nausea,
      vomiting, and hematologic toxicities were common. The combination produced more
      grade 3 to 4 leukopenia (62% v 40%), thrombocytopenia (14% v 2%), anemia (22% v
      4%), and nausea/vomiting (13% v 3%). CONCLUSION: Adding cisplatin to doxorubicin
      in advanced endometrial carcinoma improves RR and PFS with a negligible impact on
      OS and produces increased toxicity. These results have served as a building block
      for subsequent phase III trials in patients with disseminated and high-risk
      limited endometrial carcinoma.

PMID- 15459210
TI  - Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine
      or mitomycin C plus vinblastine in women with taxane-refractory advanced breast
      cancer.
AB  - PURPOSE: To compare the efficacy of pegylated liposomal doxorubicin (PLD) with
      that of a common salvage regimen (comparator) in patients with taxane-refractory
      advanced breast cancer. PATIENTS AND METHODS: Following failure of a first- or
      second-line taxane-containing regimen for metastatic disease, 301 women were
      randomly assigned to receive PLD (50 mg/m(2) every 28 days); or comparator
      vinorelbine (30 mg/m(2) weekly) or mitomycin C (10 mg/m(2) day 1 and every 28
      days) plus vinblastine (5 mg/m(2) day 1, day 14, day 28, and day 42) every 6 to 8
      weeks. Patients were stratified before random assignment based on number of
      previous chemotherapy regimens for metastatic disease and presence of bone
      metastases only. RESULTS: Progression-free survival (PFS) and overall survival
      (OS) were similar for PLD and comparator (PFS: hazard ratio [HR], 1.26; 95% CI,
      0.98 to 1.62; P =.11; median, 2.9 months [PLD] and 2.5 months [comparator]; OS:
      HR, 1.05; 95% CI, 0.82 to 1.33; P =.71; median, 11.0 months [PLD] and 9.0 months
      [comparator]). In anthracycline-naive patients, PFS was somewhat longer with PLD,
      relative to the comparator (n = 44; median PFS, 5.8 v 2.1 months; HR, 2.40; 95%
      CI, 1.16 to 4.95; P =.01). Most frequently reported adverse events were nausea
      (23% to 31%), vomiting (17% to 20%), and fatigue (9% to 20%) and were similar
      among treatment groups. PLD-treated patients experienced more palmar-plantar
      erythrodysesthesia (37%; 18% grade 3, 1 patient grade 4) and stomatitis (22%; 5%
      grades 3/4). Neuropathy (11%), constipation (16%), and neutropenia (14%) were
      more common with vinorelbine. Alopecia was low in both the PLD and vinorelbine
      groups (3% and 5%). CONCLUSION: PLD has efficacy comparable to that of common
      salvage regimens in patients with taxane-refractory metastatic breast cancer,
      thereby representing a useful therapeutic option.

PMID- 15459213
TI  - Phase I trial of intrathecal liposomal cytarabine in children with neoplastic
      meningitis.
AB  - PURPOSE: We performed a phase I trial of intrathecal (IT) liposomal cytarabine
      (DepoCyt; Enzon Pharmaceuticals, Piscataway, NJ and SkyePharma Inc, San Diego,
      CA) to determine the maximum-tolerated dose, the dose-limiting toxicities, and
      the plasma and CSF pharmacokinetics of IT lipsomal cytarabine in children >/= 3
      years of age with advanced meningeal malignancies. PATIENTS AND METHODS: Eighteen
      assessable patients received IT liposomal cytarabine through either an indwelling
      ventricular access device or via lumbar puncture. Liposomal cytarabine was given
      once every 2 weeks during induction, once every 4 weeks during consolidation, and
      once every 8 weeks during the maintenance phase of treatment. The initial dose
      was 25 mg, with subsequent escalations to 35 and 50 mg. CSF pharmacokinetic
      samples were obtained in a subset of patients. RESULTS: Arachnoiditis,
      characterized by fever, headache, nausea, vomiting, and back pain was noted in
      the first two patients at the 25 mg dose level. Therefore, subsequent patients
      were treated with dexamethasone, beginning the day of liposomal cytarabine
      administration and continuing for 5 days. Headache (grade 3) was dose limiting in
      two of eight patients enrolled at the 50 mg dose level. Eight of the 14 patients
      assessable for response demonstrated evidence of benefit manifest as prolonged
      disease stabilization or response. CONCLUSION: The maximum-tolerated dose and
      recommended phase II dose of liposomal cytarabine in patients between the ages of
      3 and 21 years is 35 mg, administered with dexamethasone (0.15 mg/kg/dose, twice
      a day for 5 days). A phase II trial of IT liposomal cytarabine in children with
      CNS leukemia in second or higher relapse is in development.

PMID- 15459212
TI  - Scintigraphic response by 123I-metaiodobenzylguanidine scan correlates with event
      free survival in high-risk neuroblastoma.
AB  - PURPOSE: To investigate whether response to induction therapy, evaluated by
      metaiodobenzylguanadine (MIBG) and bone scintigraphy, correlates with event-free
      survival (EFS) in children with high-risk neuroblastoma (NB). PATIENTS AND
      METHODS: Twenty-nine high-risk NB patients were treated prospectively with an
      intensive induction regimen and consolidated with three cycles of high-dose
      therapy with peripheral blood stem-cell rescue. The scintigraphic response was
      evaluated by MIBG and bone scans using a semi-quantitative scoring system. The
      prognostic significance of the imaging scores at diagnosis and following
      induction therapy was evaluated. RESULTS: A trend associating worse 4-year EFS
      rates for patients with versus without osteomedullary uptake on MIBG scintigraphs
      at diagnosis was seen (35% +/- 11% v 80% +/- 18%, respectively; P =.13).
      Similarly, patients with positive bone scans at diagnosis had worse EFS than
      those with negative scans, although the difference did not receive statistical
      significance (34% +/- 10% v 83% +/- 15%, respectively; P =.06). However,
      significantly worse EFS was observed in patients with a postinduction MIBG score
      of >/= 3 compared to those with scores of less than 3 (0% v 58% +/- 11%; P
      =.002). There was no correlation between bone scan scores and outcome following
      induction therapy. CONCLUSION: MIBG scores >/= 3 following induction therapy
      identifies a subset of NB patients who are likely to relapse following three
      cycles of high-dose therapy with peripheral blood stem-cell rescue, local
      radiotherapy, and 13-cis-retinoic acid. Alternative therapeutic strategies should
      be considered for patients with a poor response to induction therapy.

PMID- 15459214
TI  - Inpatient versus outpatient management of low-risk pediatric febrile neutropenia:
      measuring parents' and healthcare professionals' preferences.
AB  - PURPOSE: Our primary objective was to describe and compare parents' and
      healthcare professionals' strength of preference scores for outpatient oral
      antibiotic relative to inpatient parenteral antibiotic treatment for low-risk
      febrile neutropenic children. Our secondary objective was to identify predictors
      of strength of preference for oral outpatient treatment. METHODS: Respondents
      were parents of children receiving cancer chemotherapy, and pediatric oncology
      healthcare professionals. First, the inpatient and outpatient options were
      described, and the respondent indicated their initially preferred option. The
      respondent next ranked how important seven factors (including "fear/anxiety" and
      "comfort") were in making their initial choice. The threshold technique was then
      used to elicit the respondent's strength of preference score for oral outpatient,
      relative to parenteral inpatient management. RESULTS: There were 75 parent and 42
      healthcare-professional respondents. There was no significant difference (P =.08)
      in the proportions of parents (40 of 75; 53%) and healthcare professionals (30 of
      42; 71%) who initially would choose outpatient management. For parents, stronger
      preference for oral outpatient therapy was associated with higher anticipated
      quality of life for the parent and child at home relative to hospital, lower
      importance rank for "fear/anxiety," and higher importance rank for "comfort."
      Conversely, for professionals, only lower importance rank for "fear/anxiety" was
      associated with higher strength of preference scores for outpatient oral
      antibiotic management. CONCLUSION: Only 53% of parents would choose outpatient
      oral antibiotic management for low-risk febrile neutropenia. Predictors of
      strength of preference scores for outpatient oral antibiotic relative to
      inpatient parenteral antibiotic treatment differed between parent and
      professional respondents.

PMID- 15459215
TI  - Pharmacogenetic risk factors for osteonecrosis of the hip among children with
      leukemia.
AB  - PURPOSE: One of the adverse effects of therapy for acute lymphoblastic leukemia
      (ALL) is osteonecrosis of the hip. Putative risk factors for osteonecrosis have
      included being female, white race, and older age. Our goal was to define possible
      genetic risk factors for osteonecrosis among children treated for newly diagnosed
      ALL. METHODS: Using a candidate gene approach, we determined the genotypes for 16
      common polymorphisms in genes likely to affect the pharmacokinetics or
      pharmacodynamics of antileukemic medications in 64 children with ALL. Therapy
      included glucocorticoids and antifolates. Magnetic resonance imaging of both hips
      was used to diagnose osteonecrosis, and was performed at similar times from the
      start of ALL therapy (P =.61) in the 25 patients with and the 39 patients without
      osteonecrosis (median, 447 days and 443 days, respectively). RESULTS: In addition
      to age older than 10 years (odds ratio [OR], 24.2; P =.0001) and white race (OR,
      11.1; P =.037), host factors for osteonecrosis included the vitamin D receptor
      FokI start site CC genotype (OR, 4.5; P =.045), and the thymidylate synthase low
      activity 2/2 enhancer repeat genotype (OR, 7.4; P =.049). CONCLUSION: Because
      folate-related and vitamin D-receptor genetic variants have been associated with
      bone and vasculature morbidity, these pharmacogenetic associations likely reflect
      the interaction of antileukemic medications with germline sensitivity to drug
      actions, and might identify ALL patients at highest risk to develop
      osteonecrosis.

PMID- 15459216
TI  - Microarray gene expression profiling of B-cell chronic lymphocytic leukemia
      subgroups defined by genomic aberrations and VH mutation status.
AB  - PURPOSE: Genomic aberrations and mutational status of the immunoglobulin variable
      heavy chain (VH) gene have been shown to be among the most important predictors
      for outcome in patients with B-cell chronic lymphocytic leukemia (B-CLL). In this
      study, we report on differential gene expression patterns that are characteristic
      for genetically defined B-CLL subtypes. MATERIALS AND METHODS: One hundred
      genetically well-characterized B-CLL samples, together with 11 healthy control
      samples, were analyzed using oligonucleotide arrays, which test for the
      expression of some 12,000 human genes. RESULTS: Aiming at microarray-based
      subclassification, class predictors were constructed using sets of differentially
      expressed genes, which yielded in zero or low misclassification rates.
      Furthermore, a significant number of the differentially expressed genes clustered
      in chromosomal regions affected by the respective genomic losses/gains. Deletions
      affecting chromosome bands 11q22-q23 and 17p13 led to a reduced expression of the
      corresponding genes, such as ATM and p53, while trisomy 12 resulted in the
      upregulation of genes mapping to chromosome arm 12q. Using an unsupervised
      analysis algorithm, expression profiling allowed partitioning into predominantly
      VH-mutated versus unmutated patient groups; however, association of the
      expression profile with the VH mutational status could only be detected in male
      patients. CONCLUSION: The finding that the most significantly differentially
      expressed genes are located in the corresponding aberrant chromosomal regions
      indicates that a gene dosage effect may exert a pathogenic role in B-CLL. The
      significant difference in the partitioning of male and female B-CLL samples
      suggests that the genomic signature for the VH mutational status might be sex
      related.

PMID- 15459217
TI  - Phase III double-blind placebo-controlled study of farnesyl transferase inhibitor
      R115777 in patients with refractory advanced colorectal cancer.
AB  - PURPOSE: To determine whether R115777 improves survival in patients with
      refractory advanced colorectal cancer (CRC) in a multicenter, double-blind,
      prospective randomized study. PATIENTS AND METHODS: Three hundred sixty-eight
      patients were randomly assigned to R115777 (300 mg twice daily) orally for 21
      days every 28 days or placebo in a 2:1 ratio. All patients received best
      supportive care. The primary end point was overall survival; secondary end points
      were progression free survival, tumor response, toxicity, and quality of life.
      RESULTS: The two treatment groups were well balanced for baseline demographics,
      including previous chemotherapy for advanced CRC. The median overall survival for
      R115777 was 174 days (95% CI, 157 to 198 days), and 185 days (95% CI, 158 to 238
      days) for those patients receiving placebo (P =.376). One patient achieved a
      partial response in the R115777 arm. Stable disease (> 3 months) was observed in
      24.3% patients in the R115777 group compared to 12.8% in the placebo arm. This
      did not translate into a statistically significant increase in progression-free
      survival. Overall, treatment was well tolerated. There was an increased incidence
      of reversible myelosuppression (neutropenia, thrombocytopenia), rash, and grade 1
      to 2 diarrhea in the R115777 arm. There was no statistically significant
      difference in quality of life between arms. CONCLUSION: Single agent R115777,
      given at this dose and schedule, has an acceptable toxicity profile, but does not
      improve overall survival compared to best supportive care alone in refractory
      advanced CRC.

PMID- 15459218
TI  - Clinical nature and prognosis of locally recurrent rectal cancer after total
      mesorectal excision with or without preoperative radiotherapy.
AB  - PURPOSE: To document the clinical nature and prognosis of locally recurrent
      rectal cancer after total mesorectal excision (TME) with or without 5 x 5 Gy
      preoperative radiotherapy (PRT) and to identify patient-, disease-, and treatment
      related factors associated with differences in prognosis after local recurrence.
      PATIENTS AND METHODS: For 96 Dutch patients with a local recurrence who
      participated in a multicenter randomized clinical trial, data on treatments and
      follow-up were gathered from surgeons and radiation and medical oncologists.
      Twenty-three patients (24%) had previously been treated with PRT plus TME, and 73
      patients (76%) had been treated with TME alone. Eighty-one patients (84%) were
      followed until death; median follow-up time of the alive patients after local
      recurrence was 21 months (range, 5 to 48 months). RESULTS: Survival after local
      recurrence in the PRT + TME group was significantly shorter than in the TME group
      (median survival, 6.1 v 15.9 months; hazard ratio for death, 2.1; P =.008).
      Patients with a local recurrence in the PRT + TME group had distant metastases
      more often (74% v 40%; P =.004), underwent surgical resection of local recurrence
      less often (17% v 35%; P =.11), and received radiotherapy for local recurrence at
      a total dose >/= 45 Gy less often (4% v 42%; P =.001) than patients without PRT.
      In a multivariate analysis, the difference in survival after local recurrence
      between randomization groups was no longer statistically significant (hazard
      ratio for death of PRT, 1.53; P =.16). CONCLUSION: The clinical nature and
      prognosis of patients with locally recurrent rectal cancer has changed since the
      introduction of PRT. The majority of patients who present with a local recurrence
      after previous PRT have simultaneous distant metastases, and median survival has
      decreased to 6 months.

PMID- 15459219
TI  - Identification of novel prognosticators of outcome in squamous cell carcinoma of
      the head and neck.
AB  - PURPOSE: The goal of this study was to identify chromosomal aberrations
      associated with poor outcome in patients with head and neck squamous cell
      carcinoma (HNSCC). PATIENTS AND METHODS: We assessed the global genomic
      composition of 82 HNSCCs from previously untreated patients with comparative
      genomic hybridization (CGH). The CGH data were subcategorized into individual
      cytogenetic bands. Only genomic aberrations occurring in more than 5% of cases
      were analyzed, and redundancies were eliminated. Each aberration was submitted to
      univariate analysis to assess its relationship with disease-specific survival
      (DSS). We used Monte Carlo simulations (MCS) to adjust P values for the log-rank
      approximate chi(2) statistics for each abnormality and further applied the
      Hochberg-Benjamini procedure to adjust the P values for multiple testing of the
      large number of abnormalities. We then submitted abnormalities whose univariate
      tests resulted in an adjusted P value of less than.15 together with significant
      demographic/clinical variables to stepwise Cox proportional hazards regression.
      We again verified and adjusted P values for the chi(2) approximation of the final
      model by MCS. RESULTS: CGH analysis revealed a recurrent pattern of chromosomal
      aberrations typical for HNSCC. Univariate analysis revealed 38 abnormalities that
      were correlated with DSS. After controlling for multiple comparisons and
      confounding effects of stage, five chromosomal aberrations were significantly
      associated with outcome, including amplification at 11q13, gain of 12q24, and
      losses at 5q11, 6q14, and 21q11 (MCS adjusted P =.0009 to P =.01). CONCLUSION:
      HNSCC contains a complex pattern of chromosomal aberrations. A sequential
      approach to control for multiple comparisons and effect of confounding variables
      allows the identification of clinically relevant aberrations. The significance of
      each individual abnormality merits further consideration.

PMID- 15459220
TI  - Positron emission tomography in combination with sentinel node biopsy reduces the
      rate of elective neck dissections in the treatment of oral and oropharyngeal
      cancer.
AB  - PURPOSE: To assess the impact of a diagnostic ladder including
      [(18)F]fluorodeoxyglucose positron emission tomography (PET) and
      lymphoscintigraphy guided sentinel node biopsy (LS/SNB) on neck treatment in
      patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). PATIENTS
      AND METHODS: Prospectively, 62 patients with resectable T1-3 OOSCC underwent
      computed tomography (CT) and PET. Patients without neck uptake in PET were
      defined as cN0 and were accrued for LS/SNB. Results were correlated with
      histopathology. The traditional guidelines according to CT findings were compared
      to the actual regimen and the outcome. RESULTS: Sensitivity, specificity,
      validity, and positive and negative predictive value of PET versus CT were 72% v
      89%, 82% v 77%, 79% v 80.5%, 62% v 61.5%, and 88% v 94.5% (not significant).
      Thirty-eight PET negative patients underwent LS/SNB. Sentinel lymph nodes were
      found in all 38 patients. Five patients had positive nodes (PET false-negatives)
      and underwent neck dissection (ND). Fifty-one neck sides in 36 patients who were
      CT-negative would have been treated with selective ND according to the
      guidelines, and at least 45 neck sides would have had to undergo extensive ND
      because of positive CT findings (96 of 124 neck sides). In contrast, PET in
      combination with LS/SNB spared 59 neck sides, and 41 of 124 neck sides actually
      underwent ND as a result of PET staging, LS/SNB, and intraoperative decision.
      After a median follow-up of 35 months, two patients (both cN+ve and pN+ve)
      suffered from neck relapses. CONCLUSION: Diagnostics using PET in combination
      with LS/SNB considerably reduced the number of extensive ND in OOSCC as compared
      to CT without locoregional hazard.

PMID- 15459221
TI  - Matched-pair analysis of survival of never smokers and ever smokers with squamous
      cell carcinoma of the head and neck.
AB  - PURPOSE: To compare survival rates between patients with squamous cell carcinoma
      of the head and neck (SCCHN) without a history of smoking (never smokers) and
      those with a current or previous history of smoking (ever smokers). PATIENTS AND
      METHODS: Fifty never smokers with newly diagnosed SCCHN were matched to 50 ever
      smokers according to sex, age, tumor site, overall stage, nodal stage, and
      treatment. Survival analysis was performed using Kaplan-Meier estimates. Matched
      pair survival was compared using the Cox proportional hazards model. RESULTS: The
      never smokers had a greater overall survival (P =.020), disease-specific survival
      (P =.022), and recurrence-free survival (P =.016). Furthermore, matched-pair
      analysis demonstrated smoking was associated with a significant increase in risk
      of overall death (relative risk [RR] = 3.50; 95% CI, 1.14 to 10.77; P =.029),
      risk of death owing to disease (RR = 3.98; 95% CI, 1.11 to 14.33; P =.034), and
      risk of disease recurrence (RR = 3.29; 95% CI, 1.18 to 9.14; P =.023). Smoking
      was associated with three-fold increases in risk for overall death, death owing
      to disease, and recurrence after adjustment for cancer-associated symptom
      severity and alcohol use, but the 95% CI for these adjusted risk estimates each
      included the null. CONCLUSION: Survival differed significantly between never
      smokers and ever smokers with SCCHN. These results are not substantively
      explained by differences in cancer-associated symptoms or alcohol use, but the
      CIs are wide and some imprecision remains. Regardless, possible fundamental
      differences in SCCHN between ever smokers and never smokers may exist, and
      further molecular characterization of these tumors is needed to determine whether
      biologic differences needing targeted therapies exist.

PMID- 15459222
TI  - Serial follow-up and the prognostic significance of reverse transcriptase
      polymerase chain reaction--staged sentinel lymph nodes from melanoma patients.
AB  - PURPOSE: Reverse transcriptase-polymerase chain reaction (RT-PCR) may provide an
      extremely sensitive method for detection of occult nodal disease. We evaluated
      the role of a single-marker RT-PCR assay for tyrosinase mRNA in the detection of
      melanoma sentinel lymph node (SLN) metastases and correlated the results with
      long-term clinical outcome. PATIENTS AND METHODS: One hundred twelve patients who
      underwent SLN biopsy for melanoma were prospectively analyzed. SLNs were
      bivalved, with half of each specimen evaluated by histologic methods and the
      other half evaluated by nested RT-PCR for tyrosinase. RESULTS: Fifteen patients
      (13%) had histologically positive SLNs, all of whom were also positive by RT-PCR
      (HISTO+/PCR+). Thirty-nine patients (35%) had SLNs that were negative by both
      histology and RT-PCR (HISTO-/PCR-). Fifty-eight patients (52%) were
      histologically negative but upstaged with a positive RT-PCR result (HISTO-/PCR+).
      Initially, at a median follow-up of 42 months, recurrence rates among the three
      cohorts were statistically different (HISTO+/PCR+, 53%; HISTO-/PCR+, 14%; and
      HISTO-/PCR-, 0%). However, at a longer median follow-up (67 months), recurrence
      rates for the HISTO-/PCR+ (24%) and HISTO-/PCR- (15%) groups were no longer
      statistically different (P =.25). The median time to relapse between the HISTO
      /PCR+ and HISTO-/PCR- groups differed by 10 months (31 v 41 months,
      respectively). CONCLUSION: With extended follow-up of patients with
      histologically negative SLNs, detection of submicroscopic disease by tyrosinase
      RT-PCR does not define a subgroup that is at higher recurrence risk when compared
      with patients with RT-PCR-negative SLNs. Future studies evaluating molecular
      staging will require approximately 5 years of median follow-up to accurately
      define outcome for patients with occult melanoma metastases.

PMID- 15459223
TI  - Association between aryl hydrocarbon receptor genotype and survival in soft
      tissue sarcoma.
AB  - PURPOSE: Accumulating evidence shows that germline polymorphisms may affect
      survival in cancer. The purpose of this study was to investigate the association
      between polymorphisms in a group of candidate genes and survival with soft tissue
      sarcoma. PATIENTS AND METHODS: We measured single nucleotide polymorphisms in the
      metabolizing, detoxifying, and DNA repair pathways in 120 newly diagnosed
      patients with soft tissue sarcoma. We assessed polymorphisms in the aryl
      hydrocarbon receptor (AhR-Arg554Lys), null variants of the glutathione S
      transferase superfamily (GSTM1 and GSTT1), x-ray repair cross-complementing 1 and
      3, and Xeroderma pigmentosum, group D (XRCC1-Arg399Gln, XRCC3-Thr241Met, XPD
      Lys751Gln). We followed the patients for survival for a median of 7.6 years.
      RESULTS: Cox proportional hazards models demonstrated that a polymorphism at
      codon 554 in exon 10 of the AhR was significantly and adversely associated with
      survival (hazard ratio, 2.2; 95% CI, 1.3 to 3.9; P <.01), even while accounting
      for major clinical characteristics such as tumor grade, tumor size, anatomic
      site, and patient age. CONCLUSION: Further study of the role of the AhR
      polymorphism is warranted.

PMID- 15459224
TI  - Breast cancer treatment in older women: does getting what you want improve your
      long-term body image and mental health?
AB  - PURPOSE: Little is known about the impact of surgical treatment on body image and
      health outcomes in older breast cancer patients. The purpose of this article is
      to evaluate whether concordance between treatment received and treatment
      preferences predicts posttreatment body image and whether body image, in turn,
      affects mental health in older women with breast cancer 2 years after treatment.
      PATIENTS AND METHODS: A longitudinal cohort of 563 women who were 67 years old or
      older and who had stages I and II breast cancer were surveyed by telephone at 3,
      12, and 24 months after surgery. All women were clinically eligible for breast
      conservation. Body image was measured using questions adapted from the Cancer
      Rehabilitation Evaluation System-Short Form, and mental health was evaluated
      using a Medical Outcomes Study subscale. RESULTS: Body image was an important
      factor in treatment decisions for 31% of women. Women who received breast
      conservation had better body image 2 years after treatment than women who had
      mastectomies (P <.0001). Women who preferred breast conservation but received
      mastectomy had the poorest body image. Using generalized estimating equations, we
      found that body image, in turn, predicted 2-year mental health. CONCLUSION: Body
      image is important for many older women, and receiving treatment consistent with
      preferences about appearance was important in long-term mental health outcomes.
      Health professionals should elicit preferences about appearance from women and
      provide treatment choices in concordance with these preferences. Enhancing shared
      decision making has the potential to improve mental health in older breast cancer
      survivors.

PMID- 15459225
TI  - Effectiveness of routine visits and routine tests in detecting isolated
      locoregional recurrences after treatment for early-stage invasive breast cancer:
      a meta-analysis and systematic review.
AB  - PURPOSE: To review the effectiveness of routine visits and routine tests in
      detecting isolated locoregional recurrences in asymptomatic patients after
      treatment for early-stage invasive breast cancer. METHODS: Systematic review and
      meta-analysis. The proportion of isolated locoregional recurrences diagnosed
      during routine visits or routine tests in asymptomatic patients was compared with
      the proportion of isolated locoregional recurrences in symptomatic patients.
      RESULTS: Twelve studies that involved a total of 5,045 patients and 378 isolated
      locoregional recurrences were identified. Pooling data showed an overall estimate
      of 40% of isolated locoregional recurrences diagnosed during routine visits or
      routine tests in asymptomatic patients (95% CI, 35 to 45). Of these, 47% (95% CI,
      39 to 54) were diagnosed after mastectomy, and 36% (95% CI, 28 to 43) were
      diagnosed after breast-conserving therapy (relative risk, 1.327; 95% CI, 1.014 to
      1.738). Apart from differences in therapy, we have not been able to discern
      subgroups of patients for whom results were different. CONCLUSION: Approximately
      40% of isolated locoregional recurrences are diagnosed during routine visits and
      routine tests in asymptomatic patients treated for early-stage invasive breast
      cancer. We could not assess whether these were detected by either physical
      examination or other tests, nor if the detection of asymptomatic isolated
      recurrences had any influence on potential for cure or quality of life. As the
      overall quality of the included studies and the overall incidence of isolated
      locoregional recurrences are low, this systematic review highlights the need for
      prospective comparative studies on cost-effective strategies for the follow-up of
      patients after a diagnosis of breast cancer.

PMID- 15459226
TI  - Medical problems in patients with malignancy: case 1. Syringohydromyelia
      masquerading as malignant cord compression in a patient with small-cell lung
      cancer.

PMID- 15459227
TI  - Medical problems in patients with malignancy: case 2. Wernicke's encephalopathy:
      an unusual acute neurologic complication of lymphoma and its therapy.

PMID- 15459228
TI  - Medical problems in patients with malignancy: case 3. Ulcerating cytomegalovirus
      bronchitis in a patient with relapsed non-Hodgkin's lymphoma.

PMID- 15459229
TI  - Use of metaphor in the discourse on cancer.

PMID- 15459230
TI  - Is methylphenidate an irreplaceable therapy for the fatigued cancer patient?

PMID- 15459232
TI  - ANCA induces beta2 integrin and CXC chemokine-dependent neutrophil-endothelial
      cell interactions that mimic those of highly cytokine-activated endothelium.
AB  - Antineutrophil cytoplasm antibodies (ANCA) activate neutrophils to undergo a
      series of coordinated interactions, leading to transendothelial migration,
      eventually culminating in vascular destruction. The molecular events underlying
      neutrophil recruitment in ANCA-associated vasculitis need to be defined to enable
      effective therapeutic manipulation. A flow-based adhesion assay was used to
      investigate the role of beta2 integrins (CD11a/CD18 and CD11b/CD18) and chemokine
      receptors [CXC chemokine receptor (CXCR)1 and CXCR2] in neutrophil migration
      through the endothelium. Two endothelial models were used: a highly activated
      model stimulated with 100 U/ml tumor necrosis factor alpha (TNF-alpha) and a
      minimally activated model stimulated with 2 U/ml TNF-alpha and in which ANCA was
      present as a secondary neutrophil stimulus. CD11a/CD18, CD11b/CD18, and CXCR2
      contributed to adhesion and transendothelial migration in both models. However,
      when the endothelium was minimally activated with TNF-alpha, CD11b/CD18 played an
      important role in stabilizing adhesion induced by ANCA immunoglobulin G (IgG).
      Analysis of beta2 integrins and chemokine receptors demonstrated that ANCA IgG
      had no effect on expression levels at the neutrophil surface but enabled an
      active conformational change of CD11b/CD18. Similar molecular mechanisms control
      neutrophil adhesion and migration through highly or minimally TNF-alpha-activated
      endothelium. However, the direct ANCA-mediated neutrophil stimulation is needed
      to drive migration through minimally activated endothelium, and CD11b/CD18 is
      recruited for greater stability of adhesion during this process and can undergo
      an activatory, conformational change in response to ANCA IgG.

PMID- 15459233
TI  - Transmigrated neutrophils down-regulate the expression of VCAM-1 on endothelial
      cells and inhibit the adhesion of flowing lymphocytes.
AB  - As the first leukocytes recruited during inflammation, neutrophils are ideally
      situated to regulate the subsequent recruitment of mononuclear leukocytes. Here,
      we found that human neutrophils recruited by endothelial cells (EC), which had
      been stimulated with tumor necrosis factor alpha for 4 h, inhibited the adhesion
      of flowing, mixed mononuclear cells or purified lymphocytes over the subsequent
      20 h but did not affect the adhesion of a secondary bolus of neutrophils. The
      degree of inhibition of lymphocyte adhesion increased with the duration of
      neutrophil-EC contact and with the number of recruited neutrophils. Antibody
      blocking studies showed that lymphocyte adhesion was mediated predominantly by
      vascular cell adhesion molecule-1 (VCAM-1). Recruited neutrophils reduced the EC
      expression of VCAM-1 but not intercellular adhesion molecule-1 (ICAM-1) or E
      selectin in a manner that mirrored the time- and number-dependent reduction in
      lymphocyte adhesion. VCAM-1 was not shed into the culture supernatant, and a
      panel of protease inhibitors was unable to reverse its down-regulation,
      indicating that it was not proteolytically degraded by neutrophils. In EC that
      had been in contact with neutrophils, the mRNA message for VCAM-1 but not ICAM-1
      was down-regulated, indicating that alterations in transcriptional activity were
      responsible for the reduction in VCAM-1. Thus, under some inflammatory milieu,
      neutrophils may delay the recruitment of mononuclear leukocytes by regulating the
      expression of EC adhesion receptors.

PMID- 15459234
TI  - CD93 interacts with the PDZ domain-containing adaptor protein GIPC: implications
      in the modulation of phagocytosis.
AB  - CD93 was originally identified as a myeloid cell-surface marker and subsequently
      associated with an ability to modulate phagocytosis of suboptimally opsonized
      immunoglobulin G and complement particles in vitro. Recent studies using mice
      deficient in CD93 have demonstrated that this molecule modulates phagocytosis of
      apoptotic cells in vivo. To investigate signal transduction mechanisms mediated
      by CD93, CD93 cytoplasmic tail (CYTO)-binding proteins were identified in a yeast
      two-hybrid screen. Fifteen of 34 positive clones contained a splice variant or a
      partial cDNA encoding GIPC, a PSD-95/Dlg/ZO-1 (PDZ) domain-containing protein,
      shown previously to regulate cytoskeletal dynamics. A single clone of the N
      terminal kinase-like protein p105 and an uncharacterized stem cell transcript
      also showed specificity for binding to the CYTO by yeast two-hybrid. Using the
      yeast two-hybrid system and an in vitro glutathione S-transferase fusion protein
      binding assay, the binding of GIPC to the CYTO was shown to involve a newly
      identified class I PDZ-binding domain in the CD93 carboxyl terminus. Four
      positively charged amino acids in the juxtamembrane domain of CD93 were shown to
      be critical in stabilizing these interactions. Treatment of human monocytes with
      a cell-permeable peptide encoding the C-terminal 11 amino acids of CD93 resulted
      in an enhancement of phagocytosis, supporting the hypothesis that this protein
      protein interaction domain is involved in the modulation of phagocytosis. These
      protein interactions may participate as molecular switches in modulating cellular
      phagocytic activity.

PMID- 15459235
TI  - Recombinant HLA-G5 and -G6 drive U937 myelomonocytic cell production of TGF
      beta1.
AB  - Throughout human pregnancy, activated maternal macrophages producing anti
      inflammatory cytokines comprise a stable cell population in the uterus. This
      organ is also massively infiltrated with semiallogeneic, placenta-derived,
      invasive cytotrophoblast cells, which produce membrane and soluble isoforms of
      human leukocyte antigen (HLA)-G. Here, we investigated the possibility that two
      soluble isoforms of HLA-G, HLA-G5 and -G6, program macrophage production of
      cytokines. The model system consisted of human U937 myelomonocytic cells treated
      with phorbol 12-myristate 13-acetate (PMA) and interferon-gamma (IFN-gamma),
      which induced differentiation and activation but did not affect their viability
      or decrease their expression of the two inhibitory immunoglobulin-like transcript
      (ILT) receptors for HLA-G, ILT2 and ILT4. Exposure of the PMA/IFN-gamma-treated
      U937 cells to increasing concentrations of recombinant HLA-G5 or -G6 (rG5 and
      rG6) stimulated effects common to the two isoforms. High doses of both
      significantly decreased interleukin (IL)-10 and dramatically increased
      transforming growth factor-beta1. Differential effectiveness between the isoforms
      was demonstrated in dose-response studies, as was differential binding to ILT2
      and ILT4 in receptor-blocking studies. No effects on production of IL-4, IL-1
      receptor antagonist, IL-15, tumor necrosis factor alpha, IL-1beta, or IL-6 were
      observed. Collectively, the results are consistent with the postulate that
      environmental programming of decidual macrophages may be dictated in part by
      their proximity to soluble HLA-G-producing fetal cytotrophoblast cells.

PMID- 15459236
TI  - Circulation kinetics and organ distribution of Hb-vesicles developed as a red
      blood cell substitute.
AB  - Phospholipid vesicles encapsulating concentrated human hemoglobin (Hb-vesicles,
      HbV), also known as liposomes, have a membrane structure similar to that of red
      blood cells (RBCs). These vesicles circulate in the bloodstream as an oxygen
      carrier, and their circulatory half-life times (t(1/2)) and biodistribution are
      fundamental characteristics required for representation of their efficacy and
      safety as a RBC substitute. Herein, we report the pharmacokinetics of HbV and
      empty vesicles (EV) that do not contain Hb, in rats and rabbits to evaluate the
      potential of HbV as a RBC substitute. The samples were labeled with technetium
      99m and then intravenously infused into animals at 14 ml/kg to measure the
      kinetics of HbV elimination from blood and distribution to the organs. The t(1/2)
      values were 34.8 and 62.6 h for HbV and 29.3 and 57.3 h for EV in rats and
      rabbits, respectively. At 48 h after infusion, the liver, bone marrow, and spleen
      of both rats and rabbits had significant concentrations of HbV and EV, and the
      percentages of the infused dose in these three organs were closely correlated to
      the circulatory half-life times in elimination phase (t(1/2beta)). Furthermore,
      the milligrams of HbV per gram of tissue correlated well between rats and
      rabbits, suggesting that the balance between organ weight and body weight is a
      fundamental factor determining the pharmacokinetics of HbV. This factor could be
      used to estimate the biodistribution and the circulation time of HbV in humans,
      which is estimated to be equal to that in rabbit.

PMID- 15459237
TI  - Induction of drug metabolism by forskolin: the role of the pregnane X receptor
      and the protein kinase a signal transduction pathway.
AB  - An extract of the plant Coleus forskohlii has been used for centuries in
      Ayurvedic medicine to treat various diseases such as hypothyroidism, heart
      disease, and respiratory disorders. Additionally, complex herbal mixtures
      containing this extract are gaining popularity in United States for their
      putative "fat-burning" properties. The active ingredient in C. forskohlii extract
      is the diterpene compound forskolin. Forskolin is a widely used biochemical tool
      that activates adenyl cyclase, thereby increasing intracellular concentration of
      cAMP and thus activating the protein kinase A (PKA) signal transduction pathway.
      We show herein that both forskolin and its nonadenyl cyclase-activating analog
      1,9 dideoxyforskolin induce CYP3A gene expression in primary hepatocytes by
      functioning as agonists of the pregnane X receptor (PXR). We show that activation
      of PKA signaling potentiates PXR-mediated induction of CYP3A gene expression in
      cultured hepatocytes and increases the strength of PXR-coactivator protein
      protein interaction in cell-based assays. Kinase assays show that PXR can serve
      as a substrate for catalytically active PKA in vitro. Our data provide important
      insights into the molecular mechanism of both the PKA-dependent and -independent
      effects of forskolin on the expression of drug-metabolizing enzymes in liver.
      Finally, our data suggest that herbal therapy with C. forskohlii extract should
      be approached cautiously due to the potential for herb-drug interactions in
      patients on combination therapy.

PMID- 15459238
TI  - Cooperative effect of S4-S5 loops in domains D3 and D4 on fast inactivation of
      the Na+ channel.
AB  - Cytoplasmic S4-S5 loops have been shown to be involved in fast inactivation of
      voltage-gated ion channels. We studied mutations in these loops and their
      potential cooperative effects in domains D3 (N1151C, A1152C, I1160C/A) and D4
      (F1473C, L1482C/A) of the human skeletal muscle Na(+) channel alpha-subunit
      (hNa(v)1.4) using expression in tsA201 cells and the whole cell patch-clamp
      technique. All cysteine mutations were accessible to intracellularly applied
      sulfhydryl reagents which considerably destabilized fast inactivation. For
      different combinations of corresponding D3/D4 double mutations, fast inactivation
      could be almost completely removed. Thermodynamic cycle analysis indicated an
      additive effect for N1151C/F1473C and a significant cooperative effect for
      I1160/L1482 double mutations. Application of oxidizing reagents such as Cu
      phenanthroline to link two cysteines via a disulfide bridge did not reveal
      evidence for a direct physical interaction of cysteines in D3 and D4. In addition
      to the pronounced alterations of fast inactivation, mutations of I1160 shifted
      steady-state activation in the hyperpolarizing direction and slowed the kinetics
      of both activation and deactivation. Sulfhydryl reagents had charge-dependent
      effects on I1160C suggesting interaction with negative charges in another protein
      region. We conclude that fast inactivation of the Na(+) channel involves both S4
      S5 loops in D3 and D4 in a cooperative manner. D3/S4-S5 also plays an important
      role in activation and deactivation.

PMID- 15459239
TI  - NMDA receptors induce somatodendritic secretion in hypothalamic neurones of
      lactating female rats.
AB  - Many neurones in the mammalian brain are known to release the content of their
      vesicles from somatodendritic locations. These vesicles usually contain
      retrograde messengers that modulate network properties. The back-propagating
      action potential is thought to be the principal physiological stimulus that
      evokes somatodendritic release. In contrast, here we show that calcium influx
      through NMDA receptor (NMDAR) channels, in the absence of postsynaptic cell
      firing, is also able to induce vesicle fusion from non-synaptic sites in
      nucleated outside-out patches of dorsomedial supraoptic nucleus (SON) neurones of
      adult female rats, in particular during their reproductive stages. The
      physiological significance of this mechanism was characterized in intact brain
      slices, where NMDAR-mediated release of oxytocin was shown to retrogradely
      inhibit presynaptic GABA release, in the absence of postsynaptic cell firing.
      This implies that glutamatergic synaptic input in itself is sufficient to elicit
      the release of oxytocin, which in turn acts as a retrograde messenger leading to
      the depression of nearby GABA synapses. In addition, we found that during
      lactation, when oxytocin demand is high, NMDA-induced oxytocin release is up
      regulated compared to that in non-reproductive rats. Thus, in the hypothalamus,
      local signalling back and forth between pre- and postsynaptic compartments and
      between different synapses may occur independently of the firing activity of the
      postsynaptic neurone.

PMID- 15459240
TI  - The effect of simulated ischaemia on spontaneous GABA release in area CA1 of the
      juvenile rat hippocampus.
AB  - An early consequence of brain energy deprivation is an increase in the frequency
      of spontaneous inhibitory and excitatory postsynaptic currents (sIPSCs and
      sEPSCs), which may disrupt neural information processing. This increase in
      spontaneous transmitter release has been reported to occur in calcium-free
      solution and has been attributed either to calcium release from internal stores
      or to a direct effect of hypoxia on the transmitter release mechanism. Here we
      investigate the mechanism of the increase in sIPSC frequency that occurs in area
      CA1 of rat hippocampus during simulated ischaemia, by making patch-clamp
      recordings from CA1 pyramidal neurones. When recording in whole-cell mode,
      exposure to ischaemic solution increased the sIPSC frequency 30-fold (to 49 Hz)
      after 5 min, and doubled the sIPSC amplitude. Ischaemic sIPSCs were action
      potential independent, vesicular in origin and, contrary to the results of
      earlier studies which did not buffer extracellular calcium to a low level,
      dependent on extracellular calcium. The properties of the ischaemic sIPSCs were
      not affected by depleting intracellular stores of calcium or by blocking the
      neuronal GABA transporter GAT-1. Recording from neurones using gramicidin
      perforated patch-clamping showed a 10-fold smaller, more transient increase in
      sIPSC frequency during ischaemia, with no change of sIPSC amplitude, suggesting
      that whole-cell clamp recording increases the ischaemia-induced sIPSC rate and
      amplitude by controlling the intracellular milieu.

PMID- 15459242
TI  - Regulation of gating by negative charges in the cytoplasmic pore in the Kir2.1
      channel.
AB  - Inward rectifier K(+) channels commonly exhibit long openings (slow gating)
      punctuated by rapid open-close transitions (fast gating), suggesting that two
      separate gates may control channel open-closed transitions. Previous studies have
      suggested possible gate locations at the selectivity filter and at the 'bundle
      crossing', where the two transmembrane segments (M1 and M2) cross near the
      cytoplasmic end of the pore. Wild-type Kir2.1 channels exhibit only slow gating,
      but mutations in the cytoplasmic pore domain at E224 and E299 have been shown to
      induce fast flickery gating. Since these mutations also affect polyamine
      affinity, we conjectured that the fast gating mechanism might affect the kinetics
      of polyamine block/unblock if located more intracellularly than the polyamine
      blocking site in the pore. Neutralization of either E224 or E299 induced fast
      gating and slowed both block and unblock rates by the polyamine diamine 10. The
      slowing of polyamine block/unblock was partly relieved by raising pH from 7.2 to
      9.0, which also slowed fast gating kinetics. These findings indicate that the
      fast flickery gate is located intracellularly with respect to the polyamine pore
      plugging site near D172, thereby excluding the selectivity filter, and
      implicating the bundle crossing or more intracellular site as the gate. As
      additional proof, fast gating induced at the selectivity filter by disrupting P
      loop salt bridges in WT-E138D-E138D-WT tandem had no effect on polyamine block
      and unblock rates. The pH sensitivity of fast gating in E224 and E299 mutants was
      attributed to the protonation state of H226, since the double mutant E224Q/H226K
      induced fast gating which was pH insensitive. Moreover, introducing a negative
      charge in the 224-226 region was sufficient to prevent fast gating, since the
      double mutant E224Q/H226E rescued wild-type Kir2.1 slow gating. These
      observations implicate E224 and E299 as allosteric modulators of a fast gate,
      located at the bundle crossing or below in Kir2.1 channels. By suppressing fast
      gating, these negative charges facilitate polyamine block and unblock, which may
      be their physiologically important role.

PMID- 15459241
TI  - Developmental programming of the metabolic syndrome by maternal nutritional
      imbalance: how strong is the evidence from experimental models in mammals?
AB  - The incidence of the metabolic syndrome, a cluster of abnormalities focusing on
      insulin resistance and associated with high risk for cardiovascular disease and
      diabetes, is reaching epidemic proportions. Prevalent in both developed and
      developing countries, the metabolic syndrome has largely been attributed to
      altered dietary and lifestyle factors that favour the development of central
      obesity. However, population-based studies have suggested that predisposition to
      the metabolic syndrome may be acquired very early in development through
      inappropriate fetal or neonatal nutrition. Further evidence for developmental
      programming of the metabolic syndrome has now been suggested by animal studies in
      which the fetal environment has been manipulated through altered maternal dietary
      intake or modification of uterine artery blood flow. This review examines these
      studies and assesses whether the metabolic syndrome can be reliably induced by
      the interventions made. The validity of the different species, diets, feeding
      regimes and end-point measures used is also discussed.

PMID- 15459243
TI  - Acute desensitization of GIRK current in rat atrial myocytes is related to K+
      current flow.
AB  - We have investigated the acute desensitization of acetylcholine-activated GIRK
      current (I(K(ACh))) in cultured adult rat atrial myocytes. Acute desensitization
      of I(K(ACh)) is observed as a partial relaxation of current with a half-time of <
      5 s when muscarinic M2 receptors are stimulated by a high concentration (> 2
      micromol l(-1)) of ACh. Under this condition experimental manoeuvres that cause a
      decrease in the amplitude of I(K(ACh)), such as partial block of M2 receptors by
      atropine, intracellular loading with GDP-beta-S, or exposure to Ba2+, caused a
      reduction in desensitization. Acute desensitization was also identified as a
      decrease in current amplitude and a blunting of the response to saturating [ACh]
      (20 micromol l(-1)) when the current had been partially activated by a low
      concentration of ACh or by stimulation of adenosine A1 receptors. A reduction in
      current analogous to acute desensitization was observed when ATP-dependent K+
      current (I(K(ATP))) was activated either by mitochondrial uncoupling using 2,4
      dinitrophenole (DNP) or by the channel opener rilmakalim. Adenovirus-driven
      overexpression of Kir2.1, a subunit of constitutively active inwardly rectifying
      K+ channels, resulted in a large Ba2+-sensitive background K+ current and a
      dramatic reduction of ACh-activated current. Adenovirus-driven overexpression of
      GIRK4 (Kir3.4) subunits resulted in an increased agonist-independent GIRK current
      paralleled by a reduction in I(K(ACh)) and removal of the desensitizing
      component. These data indicate that acute desensitization depends on K+ current
      flow, independent of the K+ channel species, suggesting that it reflects a
      reduction in electrochemical driving force rather than a bona fide signalling
      mechanism. This is supported by the observation that desensitization is
      paralleled by a significant negative shift in reversal potential of I(K(ACh)).
      Since the ACh-induced hyperpolarization shows comparable desensitization
      properties as I(K(ACh)), this novel current-dependent desensitization is a
      physiologically relevant process, shaping the time course of parasympathetic
      bradycardia.

PMID- 15459244
TI  - Interhemispheric interaction between human dorsal premotor and contralateral
      primary motor cortex.
AB  - We used transcranial magnetic stimulation (TMS) in a paired pulse protocol to
      investigate interhemispheric interactions between the right dorsal premotor (dPM)
      and left primary motor cortex (M1) using interstimulus intervals of 4, 6, 8, 10,
      12, 16 and 20 ms in ten healthy subjects. A conditioning stimulus over right dPM
      at an intensity of either 90 or 110% resting motor threshold (RMT) suppressed
      motor-evoked potentials (MEPs) evoked in the first dorsal interosseous (FDI)
      muscle by stimulation of left M1. Maximum effects occurred for interstimulus
      intervals (ISIs) of 8-10 ms. There was no effect if the conditioning stimulus was
      applied 2.5 cm lateral, anterior or medial to dPM. The effect differed from
      previously described M1 interhemispheric inhibition in that the threshold for the
      latter was greater than 90% RMT, whereas stimulation of the dPM at the same
      intensity led to significant inhibition. In addition, voluntary contraction of
      the left FDI (i.e. contralateral to the conditioning TMS) enhanced
      interhemispheric inhibition from right M1 but had no effect on the inhibition
      from right dPM. Finally, conditioning to right dPM at 90% RMT reduced short
      interval intracortical inhibition (SICI; at ISI = 2 ms) in left M1 whilst there
      was no effect if the conditioning stimulus was applied to right M1. We conclude
      that conditioning TMS over dPM has effects that differ from the previous pattern
      of interhemispheric inhibition described between bilateral M1s. This may reflect
      the existence of commissural fibres between dPM and contralateral M1 that may
      play a role in bimanual coordination.

PMID- 15459245
TI  - Voltage dependence of ATP-dependent K+ current in rat cardiac myocytes is
      affected by IK1 and IK(ACh).
AB  - In this study we have investigated the voltage dependence of ATP-dependent K+
      current (I(K(ATP))) in atrial and ventricular myocytes from hearts of adult rats
      and in CHO cells expressing Kir6.2 and SUR2A. The current-voltage relation of 2,4
      dinitrophenole (DNP) -induced I(K(ATP)) in atrial myocytes and expressed current
      in CHO cells was linear in a voltage range between 0 and -100 mV. In ventricular
      myocytes, the background current-voltage relation of which is dominated by a
      large constitutive inward rectifier (I(K1)), the slope conductance of I(K(ATP))
      was reduced at membrane potentials negative to E(K) (around -50 mV), resulting in
      an outwardly rectifying I-V relation. Overexpression of Kir2.1 by adenoviral gene
      transfer, a subunit contributing to I(K1) channels, in atrial myocytes resulted
      in a large I(K1)-like background current. The I-V relation of I(K(ATP)) in these
      cells showed a reduced slope conductance negative to E(K) similar to ventricular
      myocytes. In atrial myocytes with an increased background inward-rectifier
      current through Kir3.1/Kir3.4 channels (I(K(ACh))), irreversibly activated by
      intracellular loading with GTP-gamma-S, the I-V relation of I(K(ATP)) showed a
      reduced slope negative to E(K), as in ventricular myocytes and atrial myocytes
      overexpressing Kir2.1. It is concluded that the voltage dependencies of membrane
      currents are not only dependent on the molecular composition of the charge
      carrying channel complexes but can be affected by the activity of other ion
      channel species. We suggest that the interference between inward I(K(ATP)) and
      other inward rectifier currents in cardiac myocytes reflects steady-state changes
      in K+ driving force due to inward K+ current.

PMID- 15459246
TI  - Melatonin advances the circadian timing of EEG sleep and directly facilitates
      sleep without altering its duration in extended sleep opportunities in humans.
AB  - The rhythm of plasma melatonin originating from the pineal gland and driven by
      the circadian pacemaker located in the suprachiasmatic nucleus is closely
      associated with the circadian (approximately 24 h) variation in sleep propensity
      and sleep spindle activity in humans. We investigated the contribution of
      melatonin to variation in sleep propensity, structure, duration and EEG activity
      in a protocol in which sleep was scheduled to begin during the biological day,
      i.e. when endogenous melatonin concentrations are low. The two 14 day trials were
      conducted in an environmental scheduling facility. Each trial included two
      circadian phase assessments, baseline sleep and nine 16 h sleep opportunities
      (16.00-08.00 h) in near darkness. Eight healthy male volunteers (24.4 +/- 4.4
      years) without sleep complaints were recruited, and melatonin (1.5 mg) or placebo
      was administered at the start of the first eight 16 h sleep opportunities. During
      melatonin treatment, sleep in the first 8 h of the 16 h sleep opportunities was
      increased by 2 h. Sleep per 16 h was not significantly different and approached
      asymptotic values of 8.7 h in both conditions. The percentage of rapid eye
      movement (REM) sleep was not affected by melatonin, but the percentage of stage 2
      sleep and sleep spindle activity increased, and the percentage of stage 3 sleep
      decreased. During the washout night, the melatonin-induced advance in sleep
      timing persisted, but was smaller than on the preceding treatment night and was
      consistent with the advance in the endogenous melatonin rhythm. These data
      demonstrate robust, direct sleep-facilitating and circadian effects of melatonin
      without concomitant changes in sleep duration, and support the use of melatonin
      in the treatment of sleep disorders in which the circadian melatonin rhythm is
      delayed relative to desired sleep time.

PMID- 15459247
TI  - Down-regulation does not mediate natriuretic peptide-dependent desensitization of
      natriuretic peptide receptor (NPR)-A or NPR-B: guanylyl cyclase-linked
      natriuretic peptide receptors do not internalize.
AB  - Natriuretic peptide receptor A (NPR-A/GC-A) and B (NPR-B/GC-B) are members of the
      transmembrane guanylyl cyclase family that mediate the effects of natriuretic
      peptides via the second messenger, cGMP. Despite numerous reports of these
      receptors being down-regulated in response to various pathological conditions, no
      studies have actually measured desensitization and receptor internalization in
      the same cell line. Furthermore, the ligand-dependent trafficking properties of
      NPR-A remain controversial, whereas nothing is known about the trafficking of NPR
      B. In this report, we tested whether down-regulation explains the ligand
      dependent desensitization of NPR-A and NPR-B and characterized their trafficking
      properties using a combination of hormone-binding and antibody-based assays.
      Quantitative partition analysis indicated that (125)I-atrial natriuretic peptide
      (ANP) was rapidly released into the medium after 293T cells stably expressing NPR
      A were warmed from 4 degrees to 37 degrees C. High-performance liquid
      chromatography fractionation of medium supplemented with the protease inhibitor
      phosphoramidon indicated that the (125)I-ANP was mostly intact. In contrast,
      (125)I-ANP purified from medium bathing cells expressing NPR-C, a receptor known
      to internalize natriuretic peptides, was degraded. Cleavable biotinylation and
      noncleavable biotinylation assays indicated that neither NPR-A nor NPR-B was
      internalized or degraded in response to natriuretic peptide binding. In contrast,
      agonist-dependent internalization of a G protein-coupled receptor was clearly
      apparent in the same cell line. Finally, we show that NPR-A and NPR-B are
      desensitized in cells in which they are not internalized. We suggest that
      mechanisms other than receptor down-regulation account for the desensitization of
      NPR-A and NPR-B that occurs in response to various physiological and pathological
      stimuli.

PMID- 15459248
TI  - CR6-interacting factor 1 interacts with orphan nuclear receptor Nur77 and
      inhibits its transactivation.
AB  - CR6-interacting factor 1 (CRIF1) was recently identified as a nuclear protein
      that interacts with the Gadd45 (growth arrest and DNA damage inducible 45) family
      of proteins and participates in the regulation of the G1/S phase of the cell
      cycle. However, the nuclear action of CRIF1 is largely unknown. In this study, we
      demonstrate that CRIF1 acts as a novel coregulator of transactivation of the
      orphan nuclear receptor Nur77. Both in vitro and in vivo studies show that CRIF1
      interacts with Nur77 via the Nur77 AB domain and that it dramatically inhibits
      the AB domain-mediated transactivation of Nur77. Transient transfection assays
      demonstrate that CRIF1 inhibits steroid receptor coactivator-2-mediated Nur77
      transactivation, and silencing of endogenous CRIF1 by small interfering RNA
      relieves this repression. CRIF1 possesses intrinsic repressor activities that are
      not affected by the histone deacetylase inhibitor Trichostatin A. In addition,
      overexpression of CRIF1 inhibits TSH/protein kinase A-induced Nur-responsive
      element promoter activity. CRIF1 inhibited Nur77-dependent induction of E2F1
      promoter activity, mRNA expression, and Nur77-mediated G1/S progression in cell
      cycle. These results suggest that CRIF1 acts as a repressor of the orphan nuclear
      receptor Nur77 by inhibiting AB domain-mediated transcriptional activity.

PMID- 15459249
TI  - Farnesylthiosalicylic acid inhibits mammalian target of rapamycin (mTOR) activity
      both in cells and in vitro by promoting dissociation of the mTOR-raptor complex.
AB  - The mammalian target of rapamycin (mTOR) functions with raptor and mLST8 in a
      signaling complex that controls rates of cell growth and proliferation. Recent
      results indicate that an inhibitor of the Ras signaling pathway,
      farnesylthiosalicylic acid (FTS), decreased phosphorylation of the mTOR
      effectors, PHAS-I and S6K1, in breast cancer cells. Here we show that incubating
      293T cells with FTS produced a stable change in mTOR activity that could be
      measured in immune complex kinase assays using purified PHAS-I as substrate.
      Similarly, FTS decreased the PHAS-I kinase activity of mTOR when added to cell
      extracts or to immune complexes containing mTOR. Incubating either cells or
      extracts with FTS also decreased the amount of raptor that coimmunoprecipitated
      with mTOR, although having relatively little effect on the amount of mLST8 that
      coimmunoprecipitated. The concentration effect curves of FTS for inhibition of
      mTOR activity and for dissociation of the raptor-mTOR complex were almost
      identical. Caffeine, wortmannin, LY294002, and rapamycin-FKBP12 also markedly
      inhibited mTOR activity in vitro, but unlike FTS, none of the other mTOR
      inhibitors appreciably changed the amount of raptor associated with mTOR. Thus,
      our findings indicate that FTS represents a new type of mTOR inhibitor, which
      acts by dissociating the functional mTOR-raptor signaling complex.

PMID- 15459250
TI  - Novel mode of deoxyribonucleic acid recognition by thyroid hormone receptors:
      thyroid hormone receptor beta-isoforms can bind as trimers to natural response
      elements comprised of reiterated half-sites.
AB  - Thyroid hormone receptors (TRs) regulate gene expression by binding to specific
      DNA sequences, denoted thyroid hormone response elements (TREs). The accepted
      paradigm for TRs proposes that they bind as homo- or heterodimers to TREs
      comprised of two AGGTCA half-site sequences. In the prototypic TRE, these half
      sites are arranged as direct repeats separated by a four-base spacer. This
      dimeric model of TR binding, derived from analysis of artificial DNA sequences,
      fails to explain why many natural TREs contain more than two half-sites.
      Therefore, we investigated the ability of different TR isoforms to bind to TREs
      possessing three or more half-sites. We report that the TRbeta isoforms (TRbeta0,
      TRbeta1, TRbeta2), but not TRalpha1, can bind to reiterated DNA elements, such as
      the rat GH-TRE, as complexes trimeric or greater in size. The TRbeta0 isoform, in
      particular, formed homo- and heterotrimers (with the retinoid X receptor) with
      high efficiency and cooperativity, and TRbeta0 preferentially used reporters
      containing these reiterated elements to drive gene expression in vivo. Our data
      demonstrate that TRbeta isoforms can form multimeric receptor complexes on
      appropriately reiterated DNA response elements, providing a functional
      distinction between the TR isoforms and an explanation for TREs possessing three
      or more half-sites.

PMID- 15459251
TI  - Glucagon stimulates exocytosis in mouse and rat pancreatic alpha-cells by binding
      to glucagon receptors.
AB  - Glucagon, secreted by the pancreatic alpha-cells, stimulates insulin secretion
      from neighboring beta-cells by cAMP- and protein kinase A (PKA)-dependent
      mechanisms, but it is not known whether glucagon also modulates its own
      secretion. We have addressed this issue by combining recordings of membrane
      capacitance (to monitor exocytosis) in individual alpha-cells with biochemical
      assays of glucagon secretion and cAMP content in intact pancreatic islets, as
      well as analyses of glucagon receptor expression in pure alpha-cell fractions by
      RT-PCR. Glucagon stimulated cAMP generation and exocytosis dose dependently with
      an EC50 of 1.6-1.7 nm. The stimulation of both parameters plateaued at
      concentrations beyond 10 nm of glucagon where a more than 3-fold enhancement was
      observed. The actions of glucagon were unaffected by the GLP-1 receptor
      antagonist exendin-(9-39) but abolished by des-His1-[Glu9]-glucagon-amide, a
      specific blocker of the glucagon receptor. The effects of glucagon on alpha-cell
      exocytosis were mimicked by forskolin and the stimulatory actions of glucagon and
      forskolin on exocytosis were both reproduced by intracellular application of 0.1
      mm cAMP. cAMP-potentiated exocytosis involved both PKA-dependent and -independent
      (resistant to Rp-cAMPS, an Rp-isomer of cAMP) mechanisms. The presence of the
      cAMP-binding protein cAMP-guanidine nucleotide exchange factor II in alpha-cells
      was documented by a combination of immunocytochemistry and RT-PCR and 8-(4-chloro
      phenylthio)-2'-O-methyl-cAMP, a cAMP-guanidine nucleotide exchange factor II
      selective agonist, mimicked the effect of cAMP and augmented rapid exocytosis in
      a PKA-independent manner. We conclude that glucagon released from the alpha
      cells, in addition to its well-documented systemic effects and paracrine actions
      within the islet, also represents an autocrine regulator of alpha-cell function.

PMID- 15459252
TI  - The human glucocorticoid receptor (hGR) beta isoform suppresses the
      transcriptional activity of hGRalpha by interfering with formation of active
      coactivator complexes.
AB  - The human glucocorticoid receptor (hGR) beta, a splicing variant of the classic
      receptor hGRalpha, functions as a dominant-negative inhibitor of hGRalpha. We
      explored the mechanism(s) underlying this effect of hGRbeta by evaluating the
      interactions of this isoform with known steroid receptor coactivators. We found
      that hGRbeta suppressed the transcriptional activity of both activation function
      (AF)-1 and AF-2 of hGRalpha, indicating that hGRbeta may exert its dominant
      negative effect by affecting the function of coactivators that are attracted to
      these transactivation domains. hGRbeta bound to one of the p160 coactivators, the
      glucocorticoid receptor-interacting protein 1 (GRIP1) via its preserved AF-1 but
      not via its defective AF-2 in vitro. In a chromatin immunoprecipitation assay,
      hGRbeta prevented coprecipitation of GRIP1 with hGRalpha tethered to
      glucocorticoid response elements of the endogenous tyrosine aminotransferase
      promoter, whereas deletion of the AF-1 of hGRbeta abolished this effect. In
      further experiments, overexpression of GRIP1 attenuated the suppressive effect of
      hGRbeta on hGRalpha-mediated transactivation of the mouse mammary tumor virus
      promoter. Competition for binding to glucocorticoid response elements or
      heterodimerization with hGRalpha via the D loop dimerization interface occurred,
      but they were not necessary for the suppressive effect of hGRbeta on the
      transcriptional activity of hGRalpha. Our findings suggest that hGRbeta
      suppresses the transcriptional activity of hGRalpha by competing with hGRalpha
      for binding to GRIP1, and possibly other p160 coactivators, through its preserved
      AF-1. These findings suggest that participation of hGRbeta in the formation of a
      coactivator complex renders this complex ineffective.

PMID- 15459253
TI  - Targeted expression of a dominant-negative fibroblast growth factor (FGF)
      receptor in gonadotropin-releasing hormone (GnRH) neurons reduces FGF
      responsiveness and the size of GnRH neuronal population.
AB  - Increasing evidence suggests that fibroblast growth factors (FGFs) are
      neurotrophic in GnRH neurons. However, the extent to which FGFs are involved in
      establishing a functional GnRH system in the whole organism has not been
      investigated. In this study, transgenic mice with the expression of a dominant
      negative FGF receptor mutant (FGFRm) targeted to GnRH neurons were generated to
      examine the consequence of disrupted FGF signaling on the formation of the GnRH
      system. To first test the effectiveness of this strategy, GT1 cells, a GnRH
      neuronal cell line, were stably transfected with FGFRm. The transfected cells
      showed attenuated neurite outgrowth, diminished FGF-2 responsiveness in a cell
      survival assay, and blunted activation of the signaling pathway in response to
      FGF-2. Transgenic mice expressing FGFRm in a GnRH neuron-specific manner
      exhibited a 30% reduction in GnRH neuron number, but the anatomical distribution
      of GnRH neurons was unaltered. Although these mice were initially fertile, they
      displayed several reproductive defects, including delayed puberty, reduced litter
      size, and early reproductive senescence. Overall, our results are the first to
      show, at the level of the organism, that FGFs are one of the important components
      involved in the formation and maintenance of the GnRH system.

PMID- 15459254
TI  - Statins and micronutrients: unanswered questions.

PMID- 15459255
TI  - The case for statins: has it really been made?

PMID- 15459256
TI  - Adult bone-marrow stem cells and their potential in medicine.

PMID- 15459257
TI  - Achilles tendinopathy: aetiology and management.

PMID- 15459258
TI  - Sexual activity among patients in psychiatric hospital wards.
AB  - In psychiatric hospitals, sexual activity between patients raises special
      difficulties regarding consent. We undertook a questionnaire survey of inpatients
      in the mental health units of three hospitals to identify the nature and
      frequency of sexual activity. A contemporaneous staff questionnaire was used in
      an attempt to validate the patient reports. Of the 100 patients who participated
      (response rate 60%), 30 reported engaging in some form of sexual activity
      including 10 who had sexual intercourse. All sexual intercourse was consensual,
      but only 2 respondents used condoms. Staff questionnaires suggested levels of
      sexual activity congruent with patient reports. This survey underlines the
      conflict between an individual's right to sexual expression and the need to
      protect vulnerable patients.

PMID- 15459259
TI  - 'Refusing treatment--please see': an analysis of capacity assessments carried out
      by a liaison psychiatry service.
AB  - The assessment of capacity to consent to a healthcare decision is an important
      part of day-to-day work in general hospitals. The role of liaison psychiatric
      services in assessment of capacity has not been well studied in British practice.
      We looked at all such referrals (35) to a liaison psychiatric service in a
      teaching hospital in the course of one year. The commonest referrals were
      regarding capacity to consent to a therapeutic procedure, followed by post
      discharge placement and ability to self-discharge. Organic mental disorders were
      the most frequent cause of incapacity. 20 (57%) of the referrals were for
      patients who had refused the intervention in question, and in 12 of these the
      contentious issue was resolved. Liaison psychiatric services can be useful not
      only in offering a second opinion or clarifying the influence of psychopathology
      on decision-making ability but also mediating between the patient and the
      clinical team.

PMID- 15459260
TI  - Internal iliac artery aneurysm--a cause of leg swelling and cellulitis.

PMID- 15459261
TI  - Crohn's disease and discitis.

PMID- 15459262
TI  - Facial eczema and sight-threatening glaucoma.

PMID- 15459263
TI  - Scrotal swelling in sarcoidosis.

PMID- 15459264
TI  - Breath of life: the evolution of oxygen therapy.

PMID- 15459265
TI  - The glands of Owen.

PMID- 15459266
TI  - Target tyranny.

PMID- 15459267
TI  - Surviving a viva: a guide for candidates.

PMID- 15459268
TI  - Effectiveness of cycle helmets and the ethics of legislation.

PMID- 15459269
TI  - Neurorehabilitation.

PMID- 15459270
TI  - Intestinal obstruction due to malrotation.

PMID- 15459271
TI  - Assessment of surgeons in the workplace.

PMID- 15459272
TI  - Research capacity in complementary medicine.

PMID- 15459273
TI  - A one-handed method for obtaining arterial blood.

PMID- 15459275
TI  - Art about hospitals.

PMID- 15459276
TI  - Medication errors and confusion over labelling.

PMID- 15459277
TI  - Personality disorder and somatization.

PMID- 15459278
TI  - Kikuchi's disease.

PMID- 15459279
TI  - The death of Napoleon.

PMID- 15459280
TI  - The history of St Mary's.

PMID- 15459281
TI  - Molecular barcodes detect redundancy and contamination in hairpin-bisulfite PCR.
AB  - PCR amplification of limited amounts of DNA template carries an increased risk of
      product redundancy and contamination. We use molecular barcoding to label each
      genomic DNA template with an individual sequence tag prior to PCR amplification.
      In addition, we include molecular 'batch-stamps' that effectively label each
      genomic template with a sample ID and analysis date. This highly sensitive method
      identifies redundant and contaminant sequences and serves as a reliable method
      for positive identification of desired sequences; we can therefore capture
      accurately the genomic template diversity in the sample analyzed. Although our
      application described here involves the use of hairpin-bisulfite PCR for
      amplification of double-stranded DNA, the method can readily be adapted to single
      strand PCR. Useful applications will include analyses of limited template DNA for
      biomedical, ancient DNA and forensic purposes.

PMID- 15459282
TI  - Protein evolution by codon-based random deletions.
AB  - A method to delete in-phase codons throughout a defined target region of a gene
      has been developed. This approach, named the codon-based random deletion
      (COBARDE) method, is able to delete complete codons in a random and combinatorial
      mode. Robustness, automation and fine-tuning of the mutagenesis rate are
      essential characteristics of the method, which is based on the assembly of
      oligonucleotides and on the use of two transient orthogonal protecting groups
      during the chemical synthesis. The performance of the method for protein function
      evolution was demonstrated by changing the substrate specificity of TEM-1 beta
      lactamase. Functional ceftazidime-resistant beta-lactamase variants containing
      several deleted residues inside the catalytically important omega-loop region
      were found. The results show that the COBARDE method is a useful new molecular
      tool to access previously unexplorable sequence space.

PMID- 15459283
TI  - Determination of thermodynamic parameters for HIV DIS type loop-loop kissing
      complexes.
AB  - The HIV-1 type dimerization initiation signal (DIS) loop was used as a starting
      point for the analysis of the stability of Watson-Crick (WC) base pairs in a
      tertiary structure context. We used ultraviolet melting to determine
      thermodynamic parameters for loop-loop tertiary interactions and compared them
      with regular secondary structure RNA helices of the same sequences. In 1 M Na+
      the loop-loop interaction of a HIV-1 DIS type pairing is 4 kcal/mol more stable
      than its sequence in an equivalent regular and isolated RNA helix. This
      difference is constant and sequence independent, suggesting that the rules
      governing the stability of WC base pairs in the secondary structure context are
      also valid for WC base pairs in the tertiary structure context. Moreover, the
      effect of ion concentration on the stability of loop-loop tertiary interactions
      differs considerably from that of regular RNA helices. The stabilization by Na+
      and Mg2+ is significantly greater if the base pairing occurs within the context
      of a loop-loop interaction. The dependence of the structural stability on salt
      concentration was defined via the slope of a T(m)/log [ion] plot. The short base
      paired helices are stabilized by 8 degrees C/log [Mg2+] or 11 degrees C/log
      [Na+], whereas base-paired helices forming tertiary loop-loop interactions are
      stabilized by 16 degrees C/log [Mg2+] and 26 degrees C/log [Na+]. The different
      dependence on ionic strength that is observed might reflect the contribution of
      specific divalent ion binding to the preformation of the hairpin loops poised for
      the tertiary kissing loop-loop contacts.

PMID- 15459284
TI  - Thermodynamic, kinetic and structural basis for recognition and repair of abasic
      sites in DNA by apurinic/apyrimidinic endonuclease from human placenta.
AB  - X-ray analysis of enzyme-DNA interactions is very informative in revealing
      molecular contacts, but provides neither quantitative estimates of the relative
      importance of these contacts nor information on the relative contributions of
      specific and nonspecific interactions to the total affinity of enzymes for
      specific DNA. A stepwise increase in the ligand complexity approach is used to
      estimate the relative contributions of virtually every nucleotide unit of
      synthetic DNA containing abasic sites to its affinity for apurinic/apyrimidinic
      endonuclease (APE1) from human placenta. It was found that APE1 interacts with 9
      10 nt units or base pairs of single-stranded and double-stranded
      ribooligonucleotides and deoxyribooligonucleotides of different lengths and
      sequences, mainly through weak additive contacts with internucleotide phosphate
      groups. Such nonspecific interactions of APE1 with nearly every nucleotide within
      its DNA-binding cleft provides up to seven orders of magnitude (DeltaG degrees
      approximately -8.7 to -9.0 kcal/mol) of the enzyme affinity for any DNA
      substrate. In contrast, interactions with the abasic site together with other
      specific APE1-DNA interactions provide only one order of magnitude (DeltaG
      degrees approximately -1.1 to -1.5 kcal/mol) of the total affinity of APE1 for
      specific DNA. We conclude that the enzyme's specificity for abasic sites in DNA
      is mostly due to a great increase (six to seven orders of magnitude) in the
      reaction rate with specific DNA, with formation of the Michaelis complex
      contributing to the substrate preference only marginally.

PMID- 15459286
TI  - AtmtPNPase is required for multiple aspects of the 18S rRNA metabolism in
      Arabidopsis thaliana mitochondria.
AB  - Plant mitochondria contain three rRNA genes, rrn26, rrn18 and rrn5, the latter
      two being co-transcribed. We have recently identified a polynucleotide
      phosphorylase-like protein (AtmtPNPase) in Arabidopsis mitochondria. Plants
      downregulated for AtmtPNPase expression (PNP-plants) accumulate 18S rRNA species
      polyadenylated at internal sites, indicating that AtmtPNPase is involved in 18S
      rRNA degradation. In addition, AtmtPNPase is required to degrade the leader
      sequence of 18S rRNA, a maturation by-product excised by an endonucleolytic cut
      5' to the 18S rRNA. PNP-plants also accumulate 18S rRNA precursors correctly
      processed at their 5' end but containing the intergenic sequence (ITS) between
      the 18S and 5S rRNA. Interestingly, these precursors may be polyadenylated. Taken
      together, these results suggest that AtmtPNPase initiates the degradation of the
      ITS from 18S precursors following polyadenylation. To test this, we overexpressed
      in planta a second mitochondrial exoribonuclease, AtmtRNaseII, that degrades
      efficiently unstructured RNA including poly(A) tails. This resulted also in the
      detection of 18S rRNA precursors showing that AtmtRNaseII is not able to degrade
      the ITS but can impede the action of AtmtPNPase in initiating the degradation of
      the ITS. These results show that AtmtPNPase is essential for several aspects of
      18S rRNA metabolism in Arabidopsis mitochondria.

PMID- 15459287
TI  - Adjust quality scores from alignment and improve sequencing accuracy.
AB  - In shotgun sequencing, statistical reconstruction of a consensus from alignment
      requires a model of measurement error. Churchill and Waterman proposed one such
      model and an expectation-maximization (EM) algorithm to estimate sequencing error
      rates for each assembly matrix. Ewing and Green defined Phred quality scores for
      base-calling from sequencing traces by training a model on a large amount of
      data. However, sample preparations and sequencing machines may work under
      different conditions in practice and therefore quality scores need to be
      adjusted. Moreover, the information given by quality scores is incomplete in the
      sense that they do not describe error patterns. We observe that each nucleotide
      base has its specific error pattern that varies across the range of quality
      values. We develop models of measurement error for shotgun sequencing by
      combining the two perspectives above. We propose a logistic model taking quality
      scores as covariates. The model is trained by a procedure combining an EM
      algorithm and model selection techniques. The training results in calibration of
      quality values and leads to a more accurate construction of consensus. Besides
      Phred scores obtained from ABI sequencers, we apply the same technique to
      calibrate quality values that come along with Beckman sequencers.

PMID- 15459285
TI  - A new hydrogen-bonding potential for the design of protein-RNA interactions
      predicts specific contacts and discriminates decoys.
AB  - RNA-binding proteins play many essential roles in the regulation of gene
      expression in the cell. Despite the significant increase in the number of
      structures for RNA-protein complexes in the last few years, the molecular basis
      of specificity remains unclear even for the best-studied protein families. We
      have developed a distance and orientation-dependent hydrogen-bonding potential
      based on the statistical analysis of hydrogen-bonding geometries that are
      observed in high-resolution crystal structures of protein-DNA and protein-RNA
      complexes. We observe very strong geometrical preferences that reflect
      significant energetic constraints on the relative placement of hydrogen-bonding
      atom pairs at protein-nucleic acid interfaces. A scoring function based on the
      hydrogen-bonding potential discriminates native protein-RNA structures from
      incorrectly docked decoys with remarkable predictive power. By incorporating the
      new hydrogen-bonding potential into a physical model of protein-RNA interfaces
      with full atom representation, we were able to recover native amino acids at
      protein-RNA interfaces.

PMID- 15459288
TI  - DNA-binding domain of GCN4 induces bending of both the ATF/CREB and AP-1 binding
      sites of DNA.
AB  - The interaction of proteins with DNA results, in some cases, in DNA bending, and
      this might have functional importance. However, when the protein-induced bending
      of DNA is small, its measurement presents a problem. It is shown that the
      fluorescence resonance energy transfer between fluorophores placed on the ends of
      the specially designed U-shaped DNA, which contains the DNA-binding sites at its
      central part, can be successfully used for this purpose. The lever effect of the
      arms of such U-shaped DNA ensures that the distance between the fluorophores is
      very sensitive to bending of the central part. Using this technique, it was shown
      that (i) the AP-1 and ATF/CREB binding sites of GCN4 transcription factor are pre
      bent to the same extent (approximately 12 degrees toward the major groove) and
      (ii) binding of the GCN4 DNA-binding domain (GCN4-bZIP) results in additional
      bending of both these target sites but to a greater extent at the ATF/CREB site.
      In total, in the complex with GCN4-bZIP, the ATF/CREB site is bent by (25 +/- 2)
      degrees and the AP-1 site by (20 +/- 2) degrees toward the minor groove.

PMID- 15459289
TI  - A codon window in mRNA downstream of the initiation codon where NGG codons give
      strongly reduced gene expression in Escherichia coli.
AB  - The influences on gene expression by codons at positions +2, +3, +5 and +7
      downstream of the initiation codon have been compared. Most of the +2 codons that
      are known to give low gene expression are associated with a higher expression if
      placed at the later positions. The NGG codons AGG, CGG, UGG and GGG, but not GGN
      or GNG (where N is non-G), are unique since they are associated with a very low
      gene expression also if located at positions +2, +3 and +5. All codons, including
      NGG, give a normal gene expression if placed at positions +7. The negative effect
      by the NGG codons is true for both the lacZ and 3A' model genes. The low
      expression is suggested to originate at the translational level, although it is
      not the result of mRNA secondary structure or a lowered intracellular mRNA pool.

PMID- 15459290
TI  - The Saccharomyces cerevisiae TRT2 tRNAThr gene upstream of STE6 is a barrier to
      repression in MATalpha cells and exerts a potential tRNA position effect in MATa
      cells.
AB  - A growing body of evidence suggests that genes transcribed by RNA polymerase III
      exhibit multiple functions within a chromosome. While the predominant function of
      these genes is the synthesis of RNA molecules, certain RNA polymerase III genes
      also function as genomic landmarks. Transfer RNA genes are known to exhibit extra
      transcriptional activities such as directing Ty element integration, pausing of
      replication forks, overriding nucleosome positioning sequences, repressing
      neighboring genes (tRNA position effect), and acting as a barrier to the spread
      of repressive chromatin. This study was designed to identify other tRNA loci that
      may act as barriers to chromatin-mediated repression, and focused on TRT2, a
      tRNA(Thr) adjacent to the STE6 alpha2 operator. We show that TRT2 acts as a
      barrier to repression, protecting the upstream CBT1 gene from the influence of
      the STE6 alpha2 operator in MATalpha cells. Interestingly, deletion of TRT2
      results in an increase in CBT1 mRNA levels in MATa cells, indicating a potential
      tRNA position effect. The transcription of TRT2 itself is unaffected by the
      presence of the alpha2 operator, suggesting a hierarchy that favors assembly of
      the RNA polymerase III complex versus assembly of adjacent alpha2 operator
      mediated repressed chromatin structures. This proposed hierarchy could explain
      how tRNA genes function as barriers to the propagation of repressive chromatin.

PMID- 15459291
TI  - Biochemical properties of Trypanosoma cruzi telomerase.
AB  - Trypanosomatid parasite infections have a devastating impact on human health.
      Little is known about the requirements for parasite growth during any stage of
      their complex, multi-host life cycle. In most eukaryotic organisms, sustained
      cell proliferation requires telomerase-dependent telomere length maintenance.
      Here we investigate the regulation and biochemical features of telomerase from
      Trypanosoma cruzi, the causative agent of Chagas disease. We found that T.cruzi
      telomerase is active in extracts from multiple developmental stages of the
      parasite life cycle. Detailed characterization of the enzymatic properties of
      telomerase using epimatigote-stage extract revealed a unique combination of
      substrate specificities, consistent with the evolutionary divergence of
      trypanosomes from previously established model systems for telomerase biochemical
      characterization. Results from partial purification of T.cruzi telomerase suggest
      that the catalytically active enzyme is a large ribonucleoprotein complex and
      that the internal RNA template has an atypical, cytosine-rich permutation. These
      results expand our understanding of telomerase enzymology and should encourage
      the development of parasite-specific telomerase inhibitors as a method for
      disease therapy.

PMID- 15459292
TI  - The DNA primase of Sulfolobus solfataricus is activated by substrates containing
      a thymine-rich bubble and has a 3'-terminal nucleotidyl-transferase activity.
AB  - DNA primases are responsible for the synthesis of the short RNA primers that are
      used by the replicative DNA polymerases to initiate DNA synthesis on the leading-
      and lagging-strand at the replication fork. In this study, we report the
      purification and biochemical characterization of a DNA primase (Sso DNA primase)
      from the thermoacidophilic crenarchaeon Sulfolobus solfataricus. The Sso DNA
      primase is a heterodimer composed of two subunits of 36 kDa (small subunit) and
      38 kDa (large subunit), which show sequence similarity to the eukaryotic DNA
      primase p60 and p50 subunits, respectively. The two polypeptides were co
      expressed in Escherichia coli and purified as a heterodimeric complex, with a
      Stokes radius of about 39.2 A and a 1:1 stoichiometric ratio among its subunits.
      The Sso DNA primase utilizes poly-pyrimidine single-stranded DNA templates with
      low efficiency for de novo synthesis of RNA primers, whereas its synthetic
      function is specifically activated by thymine-containing synthetic bubble
      structures that mimic early replication intermediates. Interestingly, the Sso DNA
      primase complex is endowed with a terminal nucleotidyl-transferase activity,
      being able to incorporate nucleotides at the 3' end of synthetic oligonucleotides
      in a non-templated manner.

PMID- 15459293
TI  - PhyloGenie: automated phylome generation and analysis.
AB  - Phylogenetic reconstruction is the method of choice to determine the homologous
      relationships between sequences. Difficulties in producing high-quality
      alignments, which are the basis of good trees, and in automating the analysis of
      trees have unfortunately limited the use of phylogenetic reconstruction methods
      to individual genes or gene families. Due to the large number of sequences
      involved, phylogenetic analyses of proteomes preclude manual steps and therefore
      require a high degree of automation in sequence selection, alignment,
      phylogenetic inference and analysis of the resulting set of trees. We present a
      set of programs that automates the steps from seed sequence to phylogeny and a
      utility to extract all phylogenies that match specific topological constraints
      from a database of trees. Two example applications that show the type of
      questions that can be answered by phylome analysis are provided. The generation
      and analysis of the Thermoplasma acidophilum phylome with regard to lateral gene
      transfer between Thermoplasmata and Sulfolobus, showed best BLAST hits to be far
      less reliable indicators of lateral transfer than the corresponding protein
      phylogenies. The generation and analysis of the Danio rerio phylome provided more
      than twice as many proteins as described previously, supporting the hypothesis of
      an additional round of genome duplication in the actinopterygian lineage.

PMID- 15459294
TI  - Prescription-drug prices.

PMID- 15459295
TI  - The tobacco buyout and the FDA.

PMID- 15459296
TI  - Medical marijuana, physician-assisted suicide, and the Controlled Substances Act.

PMID- 15459297
TI  - NICE work--providing guidance to the British National Health Service.

PMID- 15459298
TI  - Expecting the unexpected--drug safety, pharmacovigilance, and the prepared mind.

PMID- 15459299
TI  - Somatic mutations--not just for cancer anymore.

PMID- 15459300
TI  - Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in
      patients with persistent fever and neutropenia.
AB  - BACKGROUND: Patients with persistent fever and neutropenia often receive
      empirical therapy with conventional or liposomal amphotericin B for the
      prevention and early treatment of invasive fungal infections. Caspofungin, a
      member of the new echinocandin class of compounds, may be an effective
      alternative that is better tolerated than amphotericin B. METHODS: In this
      randomized, double-blind, multinational trial, we assessed the efficacy and
      safety of caspofungin as compared with liposomal amphotericin B as empirical
      antifungal therapy. At study entry, patients were stratified according to risk
      and according to whether they had previously received antifungal prophylaxis. A
      successful outcome was defined as the fulfillment of all components of a five
      part composite end point. RESULTS: Efficacy was evaluated in 1095 patients (556
      receiving caspofungin and 539 receiving liposomal amphotericin B). After
      adjustment for strata, the overall success rates were 33.9 percent for
      caspofungin and 33.7 percent for liposomal amphotericin B (95.2 percent
      confidence interval for the difference, -5.6 to 6.0 percent), fulfilling
      statistical criteria for the noninferiority of caspofungin. Among patients with
      baseline fungal infections, a higher proportion of those treated with caspofungin
      had a successful outcome (51.9 percent vs. 25.9 percent, P=0.04). The proportion
      of patients who survived at least seven days after therapy was greater in the
      caspofungin group (92.6 percent vs. 89.2 percent, P=0.05). Premature study
      discontinuation occurred less often in the caspofungin group than in the
      amphotericin B group (10.3 percent vs. 14.5 percent, P=0.03). The rates of
      breakthrough fungal infections and resolution of fever during neutropenia were
      similar in the two groups. Fewer patients who received caspofungin sustained a
      nephrotoxic effect (2.6 percent vs. 11.5 percent, P<0.001), an infusion-related
      event (35.1 percent vs. 51.6 percent, P<0.001), or a drug-related adverse event
      or discontinued therapy because of drug-related adverse events. CONCLUSIONS:
      Caspofungin is as effective as and generally better tolerated than liposomal
      amphotericin B when given as empirical antifungal therapy in patients with
      persistent fever and neutropenia.

PMID- 15459301
TI  - Pure red-cell aplasia and epoetin therapy.
AB  - BACKGROUND: Between 1988 and 1998, antibody-associated pure red-cell aplasia was
      reported in three patients who had undergone treatment with recombinant human
      erythropoietin (epoetin). Between 1998 and 2000, 13 such cases were reported from
      France--12 in patients who had received the Eprex formulation of epoetin alfa and
      1 in a patient who had received Neorecormon (a formulation of epoetin beta); both
      are products that are marketed outside the United States. METHODS: We obtained
      reports of epoetin-associated pure red-cell aplasia from the Food and Drug
      Administration and from the manufacturers of Eprex, Epogen (another formulation
      of epoetin alfa), and Neorecormon. The numbers of case reports and estimates of
      exposure-adjusted incidence were analyzed according to the product, the cause of
      anemia, the route of administration, the country in which pure red-cell aplasia
      was identified, and the date on which pure red-cell aplasia was reported.
      RESULTS: Between January 1998 and April 2004, 175 cases of epoetin-associated
      pure red-cell aplasia were reported for Eprex, 11 cases for Neorecormon, and 5
      cases for Epogen. Over half these cases had occurred in France, Canada, the
      United Kingdom, and Spain. Between 2001 and 2003, the estimated exposure-adjusted
      incidence was 18 cases per 100,000 patient-years for the Eprex formulation
      without human serum albumin, 6 per 100,000 patient-years for the Eprex
      formulation with human serum albumin, 1 case per 100,000 patient-years for
      Neorecormon, and 0.2 case per 100,000 patient-years for Epogen. After procedures
      were adopted to ensure appropriate storage, handling, and administration of Eprex
      to patients with chronic kidney disease, the exposure-adjusted incidence
      decreased by 83 percent worldwide. CONCLUSIONS: After the peak incidence of Eprex
      associated pure red-cell aplasia was reached in 2001, interventions designed in
      response to drug-monitoring programs worldwide resulted in a reduction of more
      than 80 percent in the incidence of pure red-cell aplasia due to Eprex.

PMID- 15459302
TI  - Autoimmune lymphoproliferative syndrome with somatic Fas mutations.
AB  - BACKGROUND: Impaired Fas-induced apoptosis of lymphocytes in vitro is a principal
      feature of the autoimmune lymphoproliferative syndrome (ALPS). We studied six
      children with ALPS whose lymphocytes had normal sensitivity to Fas-induced
      apoptosis in vitro. METHODS: Susceptibility to Fas-mediated apoptosis and the Fas
      gene were analyzed in purified subgroups of T cells and other mononuclear cells
      from six patients with ALPS type III. RESULTS: Heterozygous dominant Fas
      mutations were detected in the polyclonal double-negative T cells from all six
      patients. In two patients, these mutations were found in a fraction of CD4+ and
      CD8+ T cells, monocytes, and CD34+ hematopoietic precursors, but not in hair or
      mucosal epithelial cells. CONCLUSIONS: Somatic heterozygous mutations of Fas can
      cause a sporadic form of ALPS by allowing lymphoid precursors to resist the
      normal process of cell death.

PMID- 15459303
TI  - Inherited perforin and Fas mutations in a patient with autoimmune
      lymphoproliferative syndrome and lymphoma.
AB  - A 27-year-old man with the autoimmune lymphoproliferative syndrome and a large-B
      cell lymphoma had heterozygous mutations in the Fas and perforin (Prf1) genes.
      The Fas mutation was inherited from his healthy father and was also carried by
      his healthy brother, whereas the Prf1 mutation was inherited from his healthy
      mother. The combined effect of the two mutant genes may have contributed to the
      development of the autoimmune lymphoproliferative syndrome and lymphoma in this
      patient.

PMID- 15459304
TI  - Treatment of pulmonary arterial hypertension.

PMID- 15459305
TI  - Images in clinical medicine. Giant left atrium.

PMID- 15459306
TI  - Clinical problem-solving. Footprints.

PMID- 15459307
TI  - Antifungal therapy in patients with fever and neutropenia--more rational and less
      empirical?

PMID- 15459308
TI  - Linking physicians' pay to the quality of care--a major experiment in the United
      kingdom.

PMID- 15459309
TI  - Chitin checking--novel insights into asthma.

PMID- 15459310
TI  - Prevention of postoperative nausea and vomiting.

PMID- 15459311
TI  - Airway obstruction in chronic obstructive pulmonary disease.

PMID- 15459312
TI  - Management of chronic obstructive pulmonary disease.

PMID- 15459313
TI  - Open mesh versus laparoscopic mesh hernia repair.

PMID- 15459314
TI  - Erythropoietin, glutamate, and neuroprotection.

PMID- 15459315
TI  - Remission of a refractory, anaplastic large-cell lymphoma after treatment with
      daclizumab.

PMID- 15459316
TI  - Images in clinical medicine. Communicating hydrocephalus.

PMID- 15459317
TI  - Assigning African elephant DNA to geographic region of origin: applications to
      the ivory trade.
AB  - Resurgence of illicit trade in African elephant ivory is placing the elephant at
      renewed risk. Regulation of this trade could be vastly improved by the ability to
      verify the geographic origin of tusks. We address this need by developing a
      combined genetic and statistical method to determine the origin of poached ivory.
      Our statistical approach exploits a smoothing method to estimate geographic
      specific allele frequencies over the entire African elephants' range for 16
      microsatellite loci, using 315 tissue and 84 scat samples from forest (Loxodonta
      africana cyclotis) and savannah (Loxodonta africana africana) elephants at 28
      locations. These geographic-specific allele frequency estimates are used to infer
      the geographic origin of DNA samples, such as could be obtained from tusks of
      unknown origin. We demonstrate that our method alleviates several problems
      associated with standard assignment methods in this context, and the absolute
      accuracy of our method is high. Continent-wide, 50% of samples were located
      within 500 km, and 80% within 932 km of their actual place of origin. Accuracy
      varied by region (median accuracies: West Africa, 135 km; Central Savannah, 286
      km; Central Forest, 411 km; South, 535 km; and East, 697 km). In some cases,
      allele frequencies vary considerably over small geographic regions, making much
      finer discriminations possible and suggesting that resolution could be further
      improved by collection of samples from locations not represented in our study.

PMID- 15459318
TI  - Stimulatory G protein directly regulates hypertrophic differentiation of growth
      plate cartilage in vivo.
AB  - Stimulatory heterotrimeric G protein (Gs) transduces signals from various cell
      surface receptors to adenylyl cyclases, which generate cAMP. The alpha subunit of
      Gs (Gsalpha) is encoded by GNAS (Gnas in mice), and heterozygous Gsalpha
      inactivating mutations lead to Albright hereditary osteodystrophy. The in vivo
      role of Gsalpha in skeletogenesis is largely unknown, because of early embryonic
      lethality of mice with disruption of Gnas exon 2 (Gnas(E2-/E2-)) and the absence
      of easily detectable phenotypes in growth plate chondrocytes of heterozygous
      mutant mice (Gnas(+/E2-)). We generated chimeric mice containing wild-type cells
      and either Gnas(E2-/E2-) or Gnas(+/E2-) cells. Gnas(E2-/E2-) chondrocytes
      phenocopied PTH/PTHrP receptor (PPR)(-/-) cells by prematurely undergoing
      hypertrophy. Introduction of a transgene expressing Gsalpha, one of several gene
      products that include Gnas exon 2, into Gnas(E2-/E2-) cells prevented premature
      hypertrophy. Gsalpha mRNA expression detected by real-time RT-PCR analysis was
      reduced to approximately half that of the wild-type in both paternal and maternal
      Gnas(+/E2-) growth plate chondrocytes, indicating biallelic expression of Gsalpha
      in these cells. Hypertrophy of Gnas(+/E2-) chondrocytes was modestly but
      significantly premature in chimeric growth plates of mice containing wild-type
      and Gnas(+/E2-) cells. These data suggest that Gsalpha is the primary mediator of
      the actions of PPR in growth plate chondrocytes and that there is
      haploinsufficiency of Gsalpha signaling in Gnas(+/E2-) chondrocytes.

PMID- 15459320
TI  - Self-referred whole-body imaging: where are we now?
AB  - PURPOSE: To identify current patterns and trends of computed tomographic (CT)
      screening, including geographic data, services provided, facility type, and
      demographic characteristics. MATERIALS AND METHODS: In March 2003, self-referred
      body imaging (SRBI) centers were identified by using the Internet. Data involving
      geographic location, type of facility, services provided, and demographic
      characteristics were collected. The 2000 U.S. census data were used to compare
      center locality demographics with national patterns. Descriptive statistics, t
      tests, and regression analyses were used to evaluate data. Nonstatistical
      comparisons were made with results obtained from a previously published analysis.
      RESULTS: The number of SRBI centers totaled 161 (vs 88 in a comparative study in
      2001), and centers were distributed across 31 states and Washington, DC (vs 21 in
      2001). Racial demographics of center localities more closely resembled national
      averages in the current study, with equal percentages of whites (76.0% vs 77.1%
      nationally) and Hispanics (11.5% vs 12.5% nationally). Center localities
      continued to exhibit greater wealth and levels of education, as reflected by
      higher income per capita and median household income (P < .05), as well as by
      higher percentages of people with college and advanced degrees (P < .05). Heart
      scanning was the most commonly offered service (n = 152, 94%), followed by whole
      body scanning (n = 135, 84%), lung scanning (n = 126, 78%), and virtual
      colonoscopy (n = 88, 55%). Centers in the West were more likely to offer whole
      body and organ-specific scanning, compared with centers in other regions (P <
      .001 for virtual colonoscopy, P < .05 for head scanning). Hospital-based centers
      were less likely to offer services other than heart scanning (P < .001).
      CONCLUSION: Compared with results of a prior analysis, SRBI centers have
      increased and are distributed more widely in areas with a population that more
      closely resembles national norms. The increased trend to broaden services may
      suggest possible saturation of the preexisting market.

PMID- 15459319
TI  - Mediation of Af4 protein function in the cerebellum by Siah proteins.
AB  - We have established that the gene AF4, which had long been recognized as
      disrupted in childhood leukemia, also plays a role in the CNS. Af4 is mutated in
      the robotic mouse that is characterized by ataxia and Purkinje cell loss. To
      determine the molecular basis of this mutation, we carried out a yeast two-hybrid
      screen and show that Af4 binds the E3 ubiquitin ligases Drosophila seven in
      absentia (sina) homologues (Siah)-1a and Siah-2 in the brain. Siah-1a and Af4 are
      expressed in Purkinje cells and colocalize in the nucleus of human embryonic
      kidney 293T and P19 cells. In vitro binding assays and coimmunoprecipitation
      reveal a significant reduction in affinity between Siah-1a and robotic mutant Af4
      compared with wild-type, which correlates with the almost complete abolition of
      mutant Af4 degradation by Siah-1a. These data strongly suggest that an
      accumulation of mutant Af4 occurs in the robotic mouse due to a reduction in its
      normal turnover by the proteasome. A significant increase in the transcriptional
      activity of mutant Af4 relative to wild-type was obtained in mammalian cells,
      suggesting that the activity of Af4 is controlled through Siah-mediated
      degradation. Another member of the Af4 family, Fmr2, which is involved in mental
      handicap in humans, binds Siah proteins in a similar manner. These results
      provide evidence that a common regulatory mechanism exists that controls levels
      of the Af4/Fmr2 protein family. The robotic mouse thus provides a unique
      opportunity to understand how these proteins play a role in disorders as diverse
      as leukemia, mental retardation, and neurodegenerative disease.

PMID- 15459321
TI  - Fetal relative lung volume: quantification by using prenatal MR imaging lung
      volumetry.
AB  - PURPOSE: To retrospectively determine a biometric algorithm for calculating
      relative lung volume in fetuses with normal lungs and of a wide range of
      gestational ages by using proved independent variables and to retrospectively
      investigate the use of this algorithm in fetuses with pulmonary hypoplasia.
      MATERIALS AND METHODS: Total lung volume (TLV) was measured by using planimetry
      on single-shot rapid acquisition with relaxation enhancement magnetic resonance
      (MR) images obtained in 91 fetuses with ultrasonographically (US) normal chests
      and 28 fetuses with US-determined pulmonary hypoplasia. All fetuses were aged
      between 18 and 38 weeks gestation. Analysis of covariance was used to identify
      parameters that were not different between the fetuses with US-determined normal
      and those with US-determined abnormal chests, and these variables were used to
      construct an algorithm for calculating predicted lung volume. The relative lung
      volume-that is, the observed lung volume expressed as a percentage of the
      predicted lung volume-was then calculated in fetuses with pulmonary hypoplasia.
      RESULTS: There was no significant difference in mean maternal or gestational age
      between the two fetus groups. Stepwise regression analysis was used to generate
      the following equation for predicting fetal lung volume on the basis of
      independent biometric indexes, with a correlation coefficient of 0.93: TLV =
      (0.52 . LV) + (0.33 . BD) - (0.06 . FL) - 13.7, with TLV and liver volume (LV) in
      milliliters and biparietal diameter (BD) and femoral length (FL) in centimeters.
      In the fetuses with normal chests, relative lung volume varied between 51% and
      134%. In the fetuses with pulmonary hypoplasia, relative lung volume varied
      between 6% and 70%. CONCLUSION: The predicted lung volume in fetuses of a wide
      range of gestational ages can be calculated with a high degree of accuracy,
      enabling prenatal MR imaging lung volumetry in which relative lung volume is used
      to quantify fetal pulmonary hypoplasia.

PMID- 15459322
TI  - Entristar skin-level gastrostomy tube: primary placement with radiologic guidance
      in patients with amyotrophic lateral sclerosis.
AB  - PURPOSE: To retrospectively review the authors' experience with a radiologic
      method of primary insertion of a skin-level gastrostomy tube (Entristar; Tyco
      Healthcare, Mansfield, Mass) in patients with amyotrophic lateral sclerosis
      (ALS). MATERIALS AND METHODS: Over a 12-month period (September 2002 through
      September 2003), 25 patients with ALS (mean age, 62.4 years; age range, 41-83
      years; 15 men, 10 women) who had bulbar impairment and a body mass index of less
      than 20 kg/m(2) or weight loss of greater than 10% were selected for placement of
      an enteral feeding tube. Patients with overnight oxygen desaturation or
      respiratory acidosis were referred for placement of the Entristar tube with
      radiologic guidance. This procedure was performed with local anesthesia and
      without sedation by using a modified percutaneous lateral fluoroscopic technique
      that aided tube insertion in patients with elevation of the hemidiaphragm and a
      "high" stomach position. Technical success and immediate and delayed procedure
      complications were recorded. RESULTS: The Entristar tube was successfully
      inserted in all 25 patients. Pneumoperitoneum as an early complication was
      documented in one patient, and one patient developed a pelvic abscess that
      required drainage. Follow-up for a median of 112 days (range, 14-343 days)
      revealed superficial wound infections in four patients and weight gain in two
      patients; weight gain necessitated tube replacement in one patient. There were no
      procedure-related deaths. CONCLUSION: Radiologically guided insertion of the
      Entristar skin-level gastrostomy tube is a safe procedure in patients with ALS
      that allows the creation of a permanent feeding gastrostomy without the need for
      sedation or endoscopy.

PMID- 15459323
TI  - Coronary artery calcium score: influence of reconstruction interval at 16
      detector row CT with retrospective electrocardiographic gating.
AB  - In 30 patients, Agatston and volumetric scores were assessed by using
      retrospectively gated multi-detector row computed tomography (CT). For each
      patient, 10 data sets were created at different times and were evenly spaced
      throughout the cardiac cycle. For each reconstruction, patients were assigned a
      percentile that described the level of cardiovascular risk. Nineteen (63%) of 30
      patients could be assigned to more than one risk group depending on the
      reconstruction interval used. Agatston and volumetric scores both proved highly
      dependent on the reconstruction interval used (coefficient of variation, < or
      =63.1%) even with the most advanced CT scanners. Accurate and reproducible
      quantification of coronary calcium seems to require analysis of multiple
      reconstructions.

PMID- 15459324
TI  - Autoimmune pancreatitis: imaging features.
AB  - PURPOSE: To retrospectively determine imaging findings in patients with
      autoimmune pancreatitis. MATERIALS AND METHODS: Twenty-nine patients (25 male and
      four female; mean age, 56 years; range, 15-82 years) with histopathologic
      diagnosis of autoimmune pancreatitis were examined. Data were reviewed by two
      radiologists in consensus. Imaging findings for review included those from
      helical computed tomography (CT), 25 patients; magnetic resonance (MR) imaging
      with MR cholangiopancreatography (MRCP), four patients; endoscopic
      ultrasonography (US), 21 patients; endoscopic retrograde cholangiopancreatography
      (ERCP), 19 patients; and percutaneous transhepatic cholangiography, one patient.
      Images were analyzed for appearances of pancreas, biliary and pancreatic ducts,
      and other findings, such as peripancreatic inflammation, encasement of vessels,
      mass effect, pancreatic calcification, peripancreatic nodes, and peripancreatic
      fluid collection. Follow-up images were available in nine patients. Serologic
      markers such as serum immunoglobulin G (IgG) and antinuclear antibody levels were
      available in 12 patients. RESULTS: CT showed diffuse (n = 14) and focal (n = 7)
      enlargement of pancreas. Seven patients had minimal peripancreatic stranding,
      with lack of vascular encasement, calcification, or peripancreatic fluid
      collection. Nine patients had enlarged peripancreatic lymph nodes. MR imaging
      showed focal (n = 2) and diffuse (n = 2) enlargement with rimlike enhancement in
      one. MRCP revealed pancreatic duct strictures in two and sclerosing cholangitis
      like appearance in one. Endoscopic US showed diffuse enlargement of pancreas with
      altered echotexture in 13 patients and focal mass in the head in six. ERCP showed
      stricture of distal common bile duct in 12 patients, irregular narrowing of
      intrahepatic ducts in six, diffuse irregular narrowing of pancreatic duct in
      nine, and focal stricture of proximal pancreatic duct in six. Serologic markers
      showed increased IgG and antinuclear antibody levels in seven of 12 patients. At
      follow-up, CT abnormalities and common bile duct strictures resolved after
      steroid therapy in three patients. CONCLUSION: Features that suggest autoimmune
      pancreatitis include focal or diffuse pancreatic enlargement, with minimal
      peripancreatic inflammation and absence of vascular encasement or calcification
      at CT and endoscopic US, and diffuse irregular narrowing of main pancreatic duct,
      with associated multiple biliary strictures at ERCP.

PMID- 15459325
TI  - Soft-tissue tumors: value of static and dynamic gadopentetate dimeglumine
      enhanced MR imaging in prediction of malignancy.
AB  - PURPOSE: To prospectively evaluate static and dynamic gadopentetate dimeglumine
      enhanced magnetic resonance (MR) imaging relative to nonenhanced MR imaging in
      differentiation of benign from malignant soft-tissue lesions and to evaluate
      which MR imaging parameters are most predictive of malignancy, with associated
      interobserver variability. MATERIALS AND METHODS: One hundred forty consecutive
      patients (78 male patients [median age, 51 years], 62 female patients [median
      age, 53 years]) with a soft-tissue mass underwent nonenhanced static and dynamic
      contrast material-enhanced MR imaging. Diagnosis was based on histologic findings
      in surgical specimens (86 of 140), findings at core-needle biopsy (43 of 140), or
      results of all imaging procedures with clinical follow-up (11 of 140).
      Multivariate logistic regression analysis was used to identify the best
      combination of MR imaging parameters that might be predictive of malignancy.
      Subjective overall performance of two observers was evaluated with receiver
      operating characteristic analysis. RESULTS: For subjective overall diagnosis,
      area under the receiver operating characteristic curve, a measure for diagnostic
      accuracy, was significantly larger for combined nonenhanced and contrast-enhanced
      MR imaging than it was for nonenhanced MR imaging alone, with no significant
      difference between observers. Multivariate analysis of all lesions revealed that
      combined nonenhanced static and dynamic contrast-enhanced MR imaging parameters
      were significantly superior to nonenhanced MR imaging parameters alone and to
      nonenhanced MR imaging parameters combined with static contrast-enhanced MR
      imaging parameters in prediction of malignancy. The most discriminating
      parameters were presence of liquefaction, start of dynamic enhancement (time
      interval between start of arterial and tumor enhancement), and lesion size
      (diameter). Results for extremity lesions were the same, with one exception: With
      dynamic contrast-enhanced MR imaging parameters, diagnostic performance of one
      observer did not improve. CONCLUSION: Static and dynamic contrast-enhanced MR
      imaging, when added to nonenhanced MR imaging, improved differentiation between
      benign and malignant soft-tissue lesions.

PMID- 15459326
TI  - Multi-detector row CT: principles and practice for abdominal applications.
AB  - Abdominal imaging with multi-detector row computed tomography (CT) can be
      performed during short breath holds. On 16-channel multi-detector row CT
      scanners, the effective detector row thickness, depending on the manufacturer, is
      typically 1.0-1.5 mm, which results in a beam collimation of 16-24 mm. At a
      gantry rotation speed of 0.5 second and a pitch of 1, the table travel speed will
      be 32-48 mm/sec. At a smaller effective detector row thickness and a narrower
      beam collimation, a slightly higher pitch may be needed to obtain short-breath
      hold CT scans. Typically, transverse scans are viewed at a reconstructed section
      thickness of 3-5 mm, with thinner sections used for CT angiography and whenever
      off-axial reformations are obtained. The radiologic technique should be optimized
      according to the transverse section thickness used for interpretation, and the
      contrast material administration protocol should be optimized according to the
      clinical problem, with the scanning triggered for enhancement of a target organ.

PMID- 15459327
TI  - Baseline heart rate-adjusted electrocardiographic triggering for coronary artery
      electron-beam CT angiography.
AB  - Conventional electrocardiographic (ECG) triggering (group 1, 53 patients) was
      compared with baseline heart rate-adjusted ECG triggering (group 2, 54 patients)
      for coronary artery electron-beam computed tomographic (CT) angiography. CT
      angiographic data sets were compared blindly with conventional angiograms
      according to segment. Nonassessability of coronary artery segments was reduced
      from 35% in group 1 to 13% in group 2 (P < .001). More motion-free coronary
      artery images were obtained in group 2 than in group 1, especially in the right
      coronary artery (95% vs 67%, P < .001). Overall sensitivity and specificity for
      luminal stenosis (> or =50%) were 69% and 82% (group 1) and 76% and 92% (group 2)
      (P > .05 and P < .001, respectively). Baseline heart rate-adjusted ECG triggering
      improves image quality at coronary artery CT angiography for detection of
      coronary artery disease.

PMID- 15459328
TI  - Breast cancer metastases in liver: laser-induced interstitial thermotherapy-
      local tumor control rate and survival data.
AB  - PURPOSE: To evaluate the local tumor control rate and survival data for magnetic
      resonance (MR) imaging-guided laser ablation of breast cancer liver metastases by
      using laser-induced interstitial thermotherapy (LITT). MATERIALS AND METHODS: MR
      guided LITT was performed in 232 female patients with 578 liver metastases from
      breast cancer. Survival rates were calculated with the Kaplan-Meier method.
      Indications for the procedure were defined for patients with no more than five
      metastases, none of which were larger than 5 cm in diameter, as follows:
      recurrent liver metastases after partial liver resection (8.2%), metastases in
      both liver lobes (45.2%), locally nonresectable tumors (19%), general
      contraindications for surgery (2.6%), or refusal to undergo surgical resection
      (25%). RESULTS: Local recurrence rate at 6-month follow-up after LITT was 2.3%
      (five of 213) for metastases up to 2 cm in diameter, 4.3% (seven of 162) for
      metastases 2-3 cm in diameter, 3.2% (two of 63) for metastases 3-4 cm in
      diameter, and 1.9% (one of 52) for metastases larger than 4 cm in diameter. No
      additional local tumor progression was observed beyond 6 months. The mean
      survival rate for all treated patients, with calculation started on the date of
      diagnosis of the metastases treated with LITT, was 4.9 years (95% confidence
      interval: 4.3, 5.4). The median survival was 4.3 years; 1-year survival, 96%; 2
      year survival, 80%; 3-year survival, 63%; and 5-year survival, 41%. The mean
      survival after the first LITT treatment was 4.2 years (95% confidence interval:
      3.6, 4.8). CONCLUSION: MR-guided LITT yields high local tumor control and
      survival rates in patients with liver metastases from breast cancer.

PMID- 15459329
TI  - Small-bowel diseases: prospective evaluation of multi-detector row helical CT
      enteroclysis in 107 consecutive patients.
AB  - PURPOSE: To prospectively evaluate multi-detector row helical computed
      tomographic (CT) enteroclysis for the depiction of small-bowel diseases.
      MATERIALS AND METHODS: The study group included 107 patients who were suspected
      of having small-bowel tumor (n = 8), active inflammatory small-bowel disease (n =
      18), unexplained gastrointestinal bleeding (n = 36), refractory celiac sprue (n =
      14), and low-grade small-bowel obstruction (n = 31). A nasoenteric tube was
      positioned into the duodenojejunal junction by using fluoroscopic guidance and
      water was infused with a pressure-controlled pump. After intravenous
      administration of 120 mL of iodinated contrast material, multi-detector row
      helical CT enteroclysis images were obtained with 4 x 2.5 mm collimation (four
      detector rows and 2.5-mm section thickness). Multi-detector row helical CT
      enteroclysis findings were analyzed by two readers working in consensus. Findings
      were compared with the results of endoscopy, enteroscopy, videocapsule endoscopy,
      histopathologic analysis, or clinical follow-up. RESULTS: Multi-detector row
      helical CT enteroclysis was well tolerated in 106 patients; one patient
      complained of abdominal pain after the examination. Multi-detector row helical CT
      enteroclysis allowed the diagnosis of small-bowel masses (n = 21), active Crohn
      disease (n = 9), small-bowel tuberculosis (n = 2), small-bowel lymphoma
      complicating celiac disease (n = 4), and confirmed low-grade small-bowel
      obstruction (n = 12). Multi-detector row helical CT enteroclysis demonstrated
      normal findings in 60 patients. Sensitivity, specificity, accuracy, positive
      predictive value, and negative predictive value of multi-detector row helical CT
      enteroclysis were 100%, 95%, 97%, 94%, and 100%, respectively. CONCLUSION: Multi
      detector row helical CT enteroclysis allows depiction of small-bowel diseases in
      patients suspected of having small-bowel conditions.

PMID- 15459330
TI  - Crystal structures of possible lysine decarboxylases from Thermus thermophilus
      HB8.
AB  - TT1887 and TT1465 from Thermus thermophilus HB8 are conserved hypothetical
      proteins, and are annotated as possible lysine decarboxylases in the Pfam
      database. Here we report the crystal structures of TT1887 and TT1465 at 1.8 A and
      2.2 A resolutions, respectively, as determined by the multiwavelength anomalous
      dispersion (MAD) method. TT1887 is a homotetramer, while TT1465 is a homohexamer
      in the crystal and in solution. The structures of the TT1887 and TT1465 monomers
      contain single domains with the Rossmann fold, comprising six alpha helices and
      seven beta strands, and are quite similar to each other. The major structural
      differences exist in the N terminus of TT1465, where there are two additional
      alpha helices. A comparison of the structures revealed the elements that are
      responsible for the different oligomerization modes. The distributions of the
      electrostatic potential on the solvent-accessible surfaces suggested putative
      active sites.

PMID- 15459331
TI  - Protein self-association in crowded protein solutions: a time-resolved
      fluorescence polarization study.
AB  - The self-association equilibrium of a tracer protein, apomyoglobin (apoMb), in
      highly concentrated crowded solutions of ribonuclease A (RNase A) and human serum
      albumin (HSA), has been studied as a model system of protein interactions that
      occur in crowded macromolecular environments. The rotational diffusion of the
      tracer protein labeled with two different fluorescent dyes, 8-anilinonaphthalene
      1-sulfonate and fluorescein isothiocyanate, was successfully recorded as a
      function of the two crowder concentrations in the 50-200 mg/mL range, using
      picosecond-resolved fluorescence anisotropy methods. It was found that apoMb
      molecules self-associate at high RNase A concentration to yield a flexible dimer.
      The apparent dimerization constant, which increases with RNase A concentration,
      could also be estimated from the fractional contribution of monomeric and dimeric
      species to the total fluorescence anisotropy of the samples. In contrast, an
      equivalent mass concentration of HSA does not result in tracer dimerization. This
      different effect of RNase A and HSA is much larger than that predicted from
      simple models based only on the free volume available to apoMb, indicating that
      additional, nonspecific interactions between tracer and crowder should come into
      play. The time-resolved fluorescence polarization methods described here are
      expected to be of general applicability to the detection and quantification of
      crowding effects in a variety of macromolecules of biological relevance.

PMID- 15459332
TI  - Effect of sodium dodecyl sulfate on folding and thermal stability of acid
      denatured cytochrome c: a spectroscopic approach.
AB  - The molten globule (MG) state can be an intermediate in the protein folding
      pathway; thus, its detailed description can help understanding protein folding.
      Sodium dodecyl sulfate (SDS), an anionic surfactant that is commonly used to
      mimic hydrophobic binding environments such as cell membranes, is known to
      denature some native state proteins, including horse cytochrome c (cyt c). In
      this article, refolding of acid denatured cyt c is studied under the influence of
      SDS to form MG-like states at both low concentration and above the critical
      micelle concentration using Fourier transform Infrared (FTIR) and ultraviolet and
      visible absorption as well as fluorescence and circular dichroism (CD). Thermal
      denaturation monitored with FTIR and CD shows distinct final high temperature
      states starting from MG-like states formed with different SDS/protein ratios. The
      results suggest that the SDS/protein ratio as well as the actual SDS (or protein)
      concentration affects structure and its thermal stability. Thermal denaturation
      monitored with CD and FTIR for cyt c at neutral pH but denatured with SDS showed
      that at a high SDS/protein ratio, the thermal behavior of MG-like states formed
      at low and neutral pH are quite similar. Based on the results obtained, the
      merits of two models of the protein-surfactant structure are discussed for
      different SDS concentrations.

PMID- 15459333
TI  - Sonication of proteins causes formation of aggregates that resemble amyloid.
AB  - Despite the widespread use of sonication in medicine, industry, and research, the
      effects of sonication on proteins remain poorly characterized. We report that
      sonication of a range of structurally diverse proteins results in the formation
      of aggregates that have similarities to amyloid aggregates. The formation of
      amyloid is associated with, and has been implicated in, causing of a wide range
      of protein conformational disorders including Alzheimer's disease, Huntington's
      disease, Parkinson's disease, and prion diseases. The aggregates cause large
      enhancements in fluorescence of the dye thioflavin T, exhibit green-gold
      birefringence upon binding the dye Congo red, and cause a red-shift in the
      absorbance spectrum of Congo red. In addition, circular dichroism reveals that
      sonication-induced aggregates have high beta-content, and proteins with
      significant native alpha-helical structure show increased beta-structure in the
      aggregates. Ultrastructural analysis by electron microscopy reveals a range of
      morphologies for the sonication-induced aggregates, including fibrils with
      diameters of 5-20 nm. The addition of preformed aggregates to unsonicated protein
      solutions results in accelerated and enhanced formation of additional aggregates
      upon heating. The dye-binding and structural characteristics, as well as the
      ability of the sonication-induced aggregates to seed the formation of new
      aggregates are all similar to the properties of amyloid. These results have
      important implications for the use of sonication in food, biotechnological and
      medical applications, and for research on protein aggregation and conformational
      disorders.

PMID- 15459334
TI  - Urea modulation of beta-amyloid fibril growth: experimental studies and kinetic
      models.
AB  - Aggregation of beta-amyloid (Abeta) into fibrillar deposits is widely believed to
      initiate a cascade of adverse biological responses associated with Alzheimer's
      disease. Although it was once assumed that the mature fibril was the toxic form
      of Abeta, recent evidence supports the hypothesis that Abeta oligomers,
      intermediates in the fibrillogenic pathway, are the dominant toxic species. In
      this work we used urea to reduce the driving force for Abeta aggregation, in an
      effort to isolate stable intermediate species. The effect of urea on secondary
      structure, size distribution, aggregation kinetics, and aggregate morphology was
      examined. With increasing urea concentration, beta-sheet content and the fraction
      of aggregated peptide decreased, the average size of aggregates was reduced, and
      the morphology of aggregates changed from linear to a globular/linear mixture and
      then to globular. The data were analyzed using a previously published model of
      Abeta aggregation kinetics. The model and data were consistent with the
      hypothesis that the globular aggregates were intermediates in the amyloidogenesis
      pathway rather than alternatively aggregated species. Increasing the urea
      concentration from 0.4 M to 2 M decreased the rate of filament initiation the
      most; between 2 M and 4 M urea the largest change was in partitioning between the
      nonamyloid and amyloid pathways, and between 4 M and 6 M urea, the most
      significant change was a reduction in the rate of filament elongation.

PMID- 15459335
TI  - Alteration of the tertiary structure of the major bee venom allergen Api m 1 by
      multiple mutations is concomitant with low IgE reactivity.
AB  - We have engineered a recombinant form of the major bee venom allergen (Api m 1)
      with the final goal of reducing its IgE reactivity. This molecule (Api mut)
      contains 24 mutations and one deletion of 10 amino acids. The successive
      introduction of these sequence modifications led to a progressive loss of
      specific IgE and IgG reactivity and did not reveal any immunodominant epitopes.
      However, Api mut exhibited a clear loss of reactivity for Api m 1-specific IgE
      and IgG. Injection of Api mut into mice induced specific antibody production.
      This humoral response was as high as that induced by the Api m 1 but the cross
      reactivity of the antibodies was weak. As inferred by far UV circular dichroism,
      this mutant was correctly folded. However, near UV circular dichroism and
      denaturation curves of Api mut showed that it exhibits a dynamic tertiary
      structure and that it is a highly flexible molecule. Finally, as all the sequence
      modifications have been introduced outside the human and murine T cell epitope
      regions, we investigated its T cell properties in mice. We showed that Api mut
      specific T lymphocytes induced in vivo were stimulated in vitro by both proteins.
      These data provide new insights in the design of hypoallergenic molecules.

PMID- 15459336
TI  - Application of electrospray ionization mass spectrometry to study the hydrophobic
      interaction between the epsilon and theta subunits of DNA polymerase III.
AB  - The interactions between the N-terminal domain of the epsilon (epsilon186) and
      theta subunits of DNA polymerase III of Escherichia coli were investigated using
      electrospray ionization mass spectrometry. The epsilon186-theta complex was
      stable in 9 M ammonium actetate (pH 8), suggesting that hydrophobic interactions
      have a predominant contribution to the stability of the complex. Addition of
      primary alkanols to epsilon186-theta in 0.1 M ammonium acetate (pH 8), led to
      dissociation of the complex, as observed in the mass spectrometer. The
      concentrations of methanol, ethanol, and 1-propanol required to dissociate 50% of
      the complex were 8.9 M, 4.8 M, and 1.7 M, respectively. Closer scrutiny of the
      effect of alkanols on epsilon186, theta, and epsilon186-theta showed that
      epsilon186 formed soluble aggregates prior to precipitation, and that the
      association of epsilon186 with theta stabilized epsilon186. In-source collision
      induced dissociation experiments and other results suggested that the epsilon186
      theta complex dissociated in the mass spectrometer, and that the stability (with
      respect to dissociation) of the complex in vacuo was dependent on the solution
      from which it was sampled.

PMID- 15459337
TI  - Insertion of the cytochrome b5 heme-binding loop into an SH3 domain. Effects on
      structure and stability, and clues about the cytochrome's architecture.
AB  - Under native conditions, apocytochrome b(5) exhibits a stable core and a
      disordered heme-binding region that refolds upon association with the cofactor.
      The termini of this flexible region are in close proximity, suggesting that loop
      closure may contribute to the thermodynamic properties of the apocytochrome. A
      chimeric protein containing 43 residues encompassing the cytochrome loop was
      constructed using the cyanobacterial photosystem I accessory protein E (PsaE)
      from Synechococcus sp. PCC 7002 as a structured scaffold. PsaE has the topology
      of an SH3 domain, and the insertion was engineered to replace its 14-residue CD
      loop. NMR and optical spectroscopies showed that the hybrid protein (named EbE1)
      was folded under native conditions and that it retained the characteristics of an
      SH3 domain. NMR spectroscopy revealed that structural and dynamic differences
      were confined near the site of loop insertion. Variable-temperature 1D NMR
      spectra of EbE1 confirmed the presence of a kinetic unfolding barrier. Thermal
      and chemical denaturations of PsaE and EbE1 demonstrated cooperative, two-state
      transitions; the stability of the PsaE scaffold was found only moderately
      compromised by the insertion, with a DeltaT(m) of 8.3 degrees C, a DeltaC(m) of
      1.5 M urea, and a DeltaDeltaG degrees of 4.2 kJ/mole. The data implied that the
      penalty for constraining the ends of the inserted region was lower than the
      approximately 6.4 kJ/mole calculated for a self-avoiding chain. Extrapolation of
      these results to cytochrome b(5) suggested that the intrinsic stability of the
      folded portion of the apoprotein reflected only a small detrimental contribution
      from the large heme-binding domain.

PMID- 15459338
TI  - Promiscuous protein biotinylation by Escherichia coli biotin protein ligase.
AB  - Biotin protein ligases (BPLs) are enzymes of extraordinary specificity. BirA, the
      BPL of Escherichia coli biotinylates only a single cellular protein. We report a
      mutant BirA that attaches biotin to a large number of cellular proteins in vivo
      and to bovine serum albumin, chloramphenicol acetyltransferase, immunoglobin
      heavy and light chains, and RNAse A in vitro. The mutant BirA also self
      biotinylates in vivo and in vitro. The wild type BirA protein is much less active
      in these reactions. The biotinylation reaction is proximity-dependent in that a
      greater extent of biotinylation was seen when the mutant ligase was coupled to
      the acceptor proteins than when the acceptors were free in solution. This
      approach may permit facile detection and recovery of interacting proteins by
      existing avidin/streptavidin technology.

PMID- 15459339
TI  - Mimicry by asx- and ST-turns of the four main types of beta-turn in proteins.
AB  - Hydrogen-bonded beta-turns in proteins occur in four categories: type I (the most
      common), type II, type II', and type I'. Asx-turns resemble beta-turns, in that
      both have an NH. . .OC hydrogen bond forming a ring of 10 atoms. Serine and
      threonine side chains also commonly form hydrogen-bonded turns, here called ST
      turns. Asx-turns and ST-turns can be categorized into four classes, based on side
      chain rotamers and the conformation of the central turn residue, which are
      geometrically equivalent to the four types of beta-turns. We propose asx- and ST
      turns be named using the type I, II, I', and II' beta-turn nomenclature. Using
      this, the frequency of occurrence of both asx- and ST-turns is: type II' > type I
      > type II > type I', whereas for beta-turns it is type I > type II > type I' >
      type II'. Almost all type II asx-turns occur as a recently described three
      residue feature named an asx-nest.

PMID- 15459340
TI  - Crystal structure of human coactosin-like protein at 1.9 A resolution.
AB  - Human coactosin-like protein (CLP) shares high homology with coactosin, a
      filamentous (F)-actin binding protein, and interacts with 5LO and F-actin. As a
      tumor antigen, CLP is overexpressed in tumor tissue cells or cell lines, and the
      encoded epitopes can be recognized by cellular and humoral immune systems. To
      gain a better understanding of its various functions and interactions with
      related proteins, the crystal structure of CLP expressed in Escherichia coli has
      been determined to 1.9 A resolution. The structure features a central beta-sheet
      surrounded by helices, with two very tight hydrophobic cores on each side of the
      sheet. CLP belongs to the actin depolymerizing protein superfamily, and is
      similar to yeast cofilin and actophilin. Based on our structural analysis, we
      observed that CLP forms a polymer along the crystallographic b axis with the
      exact same repeat distance as F-actin. A model for the CLP polymer and F-actin
      binding has therefore been proposed.

PMID- 15459341
TI  - Peroxidative aggregation of alpha-synuclein requires tyrosines.
AB  - Alpha-synuclein is the main component of the intracellular protein aggregates in
      neurons of patients with Parkinson's disease. The occurrence of the disease is
      associated with oxidative damage. Although it is known that peroxidative
      chemistry leads to the aggregation of alpha-synuclein in vitro, the specific
      amino acid types of alpha-synuclein involved in this type of aggregation have not
      been identified. We show, using human cytochrome c plus H(2)O(2) as the source
      oxidative stress, that the tyrosines of alpha-synuclein are required for
      aggregation. The studies reveal the chemical basis for a crucial step in the
      aggregation process.

PMID- 15459342
TI  - Crystal structure of a dodecameric FMN-dependent UbiX-like decarboxylase (Pad1)
      from Escherichia coli O157: H7.
AB  - The crystal structure of the flavoprotein Pad1 from Escherichia coli O157:H7
      complexed with the cofactor FMN has been determined by the multiple anomalous
      diffraction method and refined at 2.0 A resolution. This protein is a paralog of
      UbiX (3-octaprenyl-4-hydroxybenzoate carboxylyase, 51% sequence identity) that
      catalyzes the third step in ubiquinone biosynthesis and to Saccharomyces
      cerevisiae Pad1 (54% identity), an enzyme that confers resistance to the
      antimicrobial compounds phenylacrylic acids through decarboxylation of these
      compounds. Each Pad1 monomer consists of a typical Rossmann fold containing a non
      covalently bound molecule of FMN. The fold of Pad1 is similar to MrsD, an enzyme
      associated with lantibiotic synthesis; EpiD, a peptidyl-cysteine decarboxylase;
      and AtHAL3a, the enzyme, which decarboxylates 4'-phosphopantothenoylcysteine to
      4'-phosphopantetheine during coenzyme A biosynthesis, all with a similar location
      of the FMN binding site at the interface between two monomers, yet each having
      little sequence similarity to one another. All of these proteins associate into
      oligomers, with a trimer forming the common structural unit in each case. In MrsD
      and EpiD, which belong to the homo-dodecameric flavin-containing cysteine
      decarboxylase (HFCD) family, these trimers associate further into dodecamers.
      Pad1 also forms dodecamers, although the association of the trimers is completely
      different, resulting in exposure of a different side of the trimer unit to the
      solvent. This exposure affects the location of the substrate binding site and,
      specifically, its access to the FMN cofactor. Therefore, Pad1 forms a separate
      family, distinguishable from the HFCD family.

PMID- 15459343
TI  - Stabilization of membranes upon interaction of amphipathic polymers with membrane
      proteins.
AB  - Amphipathic polymers derived from polysaccharides, namely hydrophobically
      modified pullulans, were previously suggested to be useful as polymeric
      substitutes of ordinary surfactants for efficient and structure-conserving
      solubilization of membrane proteins, and one such polymer, 18C(10), was optimized
      for solubilization of proteins derived from bacterial outer membranes (Duval
      Terrie et al. 2003). We asked whether a similar ability to solubilize proteins
      could also be demonstrated in eukaryotic membranes, namely sarcoplasmic reticulum
      (SR) fragments, the major protein of which is SERCA1a, an integral membrane
      protein with Ca(2+)-dependent ATPase and Ca(2+)-pumping activity. We found that
      18C(10)-mediated solubilization of these SR membranes did not occur.
      Simultaneously, however, we found that low amounts of this hydrophobically
      modified pullulan were very efficient at preventing long-term aggregation of
      these SR membranes. This presumably occurred because the negatively charged
      polymer coated the membranous vesicles with a hydrophilic corona (a property
      shared by many other amphipathic polymers), and thus minimized their
      flocculation. Reminiscent of the old Arabic gum, which stabilizes Indian ink by
      coating charcoal particles, the newly designed amphipathic polymers might
      therefore unintentionally prove useful also for stabilization of membrane
      suspensions.

PMID- 15459344
TI  - Reconstructing past climate from noisy data.
AB  - Empirical reconstructions of the Northern Hemisphere (NH) temperature in the past
      millennium based on multiproxy records depict small-amplitude variations followed
      by a clear warming trend in the past two centuries. We use a coupled atmosphere
      ocean model simulation of the past 1000 years as a surrogate climate to test the
      skill of these methods, particularly at multidecadal and centennial time scales.
      Idealized proxy records are represented by simulated grid-point temperature,
      degraded with statistical noise. The centennial variability of the NH temperature
      is underestimated by the regression-based methods applied here, suggesting that
      past variations may have been at least a factor of 2 larger than indicated by
      empirical reconstructions.

PMID- 15459345
TI  - Accumulation of Mn(II) in Deinococcus radiodurans facilitates gamma-radiation
      resistance.
AB  - Deinococcus radiodurans is extremely resistant to ionizing radiation. How this
      bacterium can grow under chronic gamma radiation [50 grays (Gy) per hour] or
      recover from acute doses greater than 10 kGy is unknown. We show that D.
      radiodurans accumulates very high intracellular manganese and low iron levels
      compared with radiation-sensitive bacteria and that resistance exhibits a
      concentration-dependent response to manganous chloride [Mn(II)]. Among the most
      radiation-resistant bacterial groups reported, Deinococcus, Enterococcus,
      Lactobacillus, and cyanobacteria accumulate Mn(II). In contrast, Shewanella
      oneidensis and Pseudomonas putida have high iron but low intracellular manganese
      concentrations and are very sensitive. We propose that Mn(II) accumulation
      facilitates recovery from radiation injury.

PMID- 15459346
TI  - Anabaena sensory rhodopsin: a photochromic color sensor at 2.0 A.
AB  - Microbial sensory rhodopsins are a family of membrane-embedded photoreceptors in
      prokaryotic and eukaryotic organisms. Structures of archaeal rhodopsins, which
      function as light-driven ion pumps or photosensors, have been reported. We
      present the structure of a eubacterial rhodopsin, which differs from those of
      previously characterized archaeal rhodopsins in its chromophore and cytoplasmic
      side portions. Anabaena sensory rhodopsin exhibits light-induced interconversion
      between stable 13-cis and all-trans states of the retinylidene protein. The ratio
      of its cis and trans chromophore forms depends on the wavelength of illumination,
      thus providing a mechanism for a single protein to signal the color of light, for
      example, to regulate color-sensitive processes such as chromatic adaptation in
      photosynthesis. Its cytoplasmic half channel, highly hydrophobic in the archaeal
      rhodopsins, contains numerous hydrophilic residues networked by water molecules,
      providing a connection from the photoactive site to the cytoplasmic surface
      believed to interact with the receptor's soluble 14-kilodalton transducer.

PMID- 15459348
TI  - The candidates speak.

PMID- 15459347
TI  - Climate. The real color of climate change?

PMID- 15459349
TI  - Epidemiology. VA advisers link Gulf War illnesses to neurotoxins.

PMID- 15459350
TI  - Fusion science. Europe may break out of ITER partnership.

PMID- 15459351
TI  - Conflict of interest. NIH proposes temporary ban on paid consulting.

PMID- 15459352
TI  - Parkfield happens.

PMID- 15459353
TI  - Planetary science. Heavy breathing on Mars?

PMID- 15459354
TI  - U.S. science budget. NSF, NASA meet 2005 request after 'bonus' from Senate panel.

PMID- 15459355
TI  - Scientific publishing. Suit seeks to ease trade embargo rules.

PMID- 15459357
TI  - Nonprofit world. Santa Fe Institute seeks president.

PMID- 15459356
TI  - Genetics. DNA reveals diatom's complexity.

PMID- 15459358
TI  - Cancer research. Pioneering prevention institute declares bankruptcy.

PMID- 15459359
TI  - Diabetes. Islet transplants face test of time.

PMID- 15459360
TI  - Research community. Science weathers the storms.

PMID- 15459361
TI  - Paleoanthropology. Dressed for success: Neandertal culture wins respect.

PMID- 15459362
TI  - Engineering of sport meeting. In volleyball, crafty players serve up an
      aerodynamic crisis.

PMID- 15459363
TI  - Engineering of sport meeting. To throw farther, waste energy.

PMID- 15459364
TI  - Engineering of sport meeting. Pulling straight to the end of the pool.

PMID- 15459365
TI  - Engineering of sport meeting. Snapshots from the meeting.

PMID- 15459366
TI  - 2004 presidential forum: Bush and Kerry offer their views on science.

PMID- 15459367
TI  - Retraction.

PMID- 15459368
TI  - GALEX and UV observations.

PMID- 15459369
TI  - Clinical trials or exploitation?

PMID- 15459370
TI  - Climate change and malaria.

PMID- 15459371
TI  - A bit of history about Edwin A. Link.

PMID- 15459372
TI  - Beyond the ivory tower. What kind of science is experimental physics?

PMID- 15459373
TI  - Structural biology. Evolution of RNA architecture.

PMID- 15459374
TI  - Applied physics. Boosting magnetoresistance in molecular devices.

PMID- 15459375
TI  - Geophysics. Are Earth's core and mantle on speaking terms?

PMID- 15459376
TI  - Virology. Src launches vaccinia.

PMID- 15459378
TI  - Climate. A stellar view on solar variations and climate.

PMID- 15459377
TI  - Cell biology. Chemical genetics hits.

PMID- 15459379
TI  - Assessing the causes of late Pleistocene extinctions on the continents.
AB  - One of the great debates about extinction is whether humans or climatic change
      caused the demise of the Pleistocene megafauna. Evidence from paleontology,
      climatology, archaeology, and ecology now supports the idea that humans
      contributed to extinction on some continents, but human hunting was not solely
      responsible for the pattern of extinction everywhere. Instead, evidence suggests
      that the intersection of human impacts with pronounced climatic change drove the
      precise timing and geography of extinction in the Northern Hemisphere. The story
      from the Southern Hemisphere is still unfolding. New evidence from Australia
      supports the view that humans helped cause extinctions there, but the correlation
      with climate is weak or contested. Firmer chronologies, more realistic ecological
      models, and regional paleoecological insights still are needed to understand
      details of the worldwide extinction pattern and the population dynamics of the
      species involved.

PMID- 15459380
TI  - Curving and frustrating flatland.
AB  - Two polymer chains that occupy equal volumes when covalently linked together at
      one end self-assemble into an alternating lamellar morphology that has a
      characteristic period dictated by the molecular weight. When such copolymers are
      confined within alumina membranes that have cylindrical pores with diameters
      comparable to the repeat period, the interaction of the blocks with the confining
      walls and the imposed curvature induces a morphological transformation to relieve
      the constraints. Here, we show a lamella-to-toroid transition, captured through
      the dissolution of the surrounding membrane.

PMID- 15459381
TI  - Maintained cardiac pumping in anoxic crucian carp.
AB  - Like most vertebrates, humans die within minutes when deprived of molecular
      oxygen (anoxia), in part because of cardiac failure. In contrast, some freshwater
      turtles can survive anoxia for months at low temperatures, but to do so, they
      drastically suppress cardiac activity and autonomic cardiovascular control.
      Although Carassius carassius, the crucian carp, shares this anoxia tolerance, we
      show that it has a unique ability among vertebrates to retain normal cardiac
      performance and autonomic cardiovascular regulation for at least 5 days of
      anoxia. These responses point to an unusual tolerance of a vertebrate heart and
      autonomic nervous system to prolonged anoxia.

PMID- 15459383
TI  - The Kondo effect in the presence of ferromagnetism.
AB  - We measured Kondo-assisted tunneling via C60 molecules in contact with
      ferromagnetic nickel electrodes. Kondo correlations persisted despite the
      presence of ferromagnetism, but the Kondo peak in the differential conductance
      was split by an amount that decreased (even to zero) as the moments in the two
      electrodes were turned from parallel to antiparallel alignment. The splitting is
      too large to be explained by a local magnetic field. However, the voltage,
      temperature, and magnetic field dependence of the signals agree with predictions
      for an exchange splitting of the Kondo resonance. The Kondo effect leads to
      negative values of magnetoresistance, with magnitudes much larger than the
      Julliere estimate.

PMID- 15459382
TI  - The genome of the diatom Thalassiosira pseudonana: ecology, evolution, and
      metabolism.
AB  - Diatoms are unicellular algae with plastids acquired by secondary endosymbiosis.
      They are responsible for approximately 20% of global carbon fixation. We report
      the 34 million-base pair draft nuclear genome of the marine diatom Thalassiosira
      pseudonana and its 129 thousand-base pair plastid and 44 thousand-base pair
      mitochondrial genomes. Sequence and optical restriction mapping revealed 24
      diploid nuclear chromosomes. We identified novel genes for silicic acid transport
      and formation of silica-based cell walls, high-affinity iron uptake, biosynthetic
      enzymes for several types of polyunsaturated fatty acids, use of a range of
      nitrogenous compounds, and a complete urea cycle, all attributes that allow
      diatoms to prosper in aquatic environments.

PMID- 15459385
TI  - Geochemical evidence for excess iron in the mantle beneath Hawaii.
AB  - Chemical interaction of Earth's mantle with the liquid outer core should
      influence the mantle's iron content. Osmium isotope ratios in Hawaiian lavas
      indicate a mass flux of </=1% core to the mantle, which is the immediate source
      of these lavas. We present precise measurements of the Fe/Mn ratio for Hawaiian
      lavas, revealing an increase of 1 to 2% in the mole fraction of iron in the
      mantle beneath Hawaii. This corresponds to a density anomaly of about 0.5%, about
      the same magnitude observed in seismic tomography models of the Pacific
      superswell region. These data also rule out a role for Mn-rich sediments as the
      source of the Hawaiian Os isotope signal.

PMID- 15459384
TI  - Extinct 244Pu in ancient zircons.
AB  - We have found evidence, in the form of fissiogenic xenon isotopes, for in situ
      decay of 244Pu in individual 4.1- to 4.2-billion-year-old zircons from the Jack
      Hills region of Western Australia. Because of its short half-life, 82 million
      years, 244Pu was extinct within 600 million years of Earth's formation. Detrital
      zircons are the only known relics to have survived from this period, and a study
      of their Pu geochemistry will allow us to date ancient metamorphic events and
      determine the terrestrial Pu/U ratio for comparison with the solar ratio.

PMID- 15459386
TI  - Toroidal triblock copolymer assemblies.
AB  - A stable phase of toroidal, or ringlike, supramolecular assemblies was formed by
      combining dilute solution characteristics critical for both bundling of like
      charged biopolymers and block copolymer micelle formation. The key to toroid
      versus classic cylinder micelle formation is the interaction of the negatively
      charged hydrophilic block of an amphiphilic triblock copolymer with a positively
      charged divalent organic counterion. This produces a self-attraction of
      cylindrical micelles that leads to toroid formation, a mechanism akin to the
      toroidal bundling of semiflexible charged biopolymers such as DNA. The toroids
      can be kinetically trapped or chemically cross-linked. Insight into the mechanism
      of toroid formation can be gained by observation of intermediate structures
      kinetically trapped during film casting.

PMID- 15459387
TI  - Multicompartment micelles from ABC miktoarm stars in water.
AB  - By combining three mutually immiscible polymeric components in a mixed-arm star
      block terpolymer architecture, we have observed the formation of a previously
      unknown class of multicompartment micelles in dilute aqueous solution. Connection
      of water-soluble poly(ethylene oxide) and two hydrophobic but immiscible
      components (a polymeric hydrocarbon and a perfluorinated polyether) at a common
      junction leads to molecular frustration when dispersed in aqueous solution. The
      incompatible hydrophobic blocks form cores that are protected from the water by
      the poly(ethylene oxide) blocks, but both are forced to make contact with the
      poly(ethylene oxide) by virtue of the chain architecture. The structures that
      emerge depend on the relative lengths of the blocks and can be tuned from
      discrete multicompartment micelles to extended wormlike structures with segmented
      cores.

PMID- 15459388
TI  - Cope's rule, hypercarnivory, and extinction in North American canids.
AB  - Over the past 50 million years, successive clades of large carnivorous mammals
      diversified and then declined to extinction. In most instances, the cause of the
      decline remains a puzzle. Here we argue that energetic constraints and pervasive
      selection for larger size (Cope's rule) in carnivores lead to dietary
      specialization (hypercarnivory) and increased vulnerability to extinction. In two
      major clades of extinct North American canids, the evolution of large size was
      associated with a dietary shift to hypercarnivory and a decline in species
      durations. Thus, selection for attributes that promoted individual success
      resulted in progressive evolutionary failure of their clades.

PMID- 15459389
TI  - Basis for structural diversity in homologous RNAs.
AB  - Large RNA molecules, such as ribozymes, fold with well-defined tertiary
      structures that are important for their activity. There are many instances of
      ribozymes with identical function but differences in their secondary structures,
      suggesting alternative tertiary folds. Here, we report a crystal structure of the
      161-nucleotide specificity domain of an A-type ribonuclease P that differs in
      secondary and tertiary structure from the specificity domain of a B-type
      molecule. Despite the differences, the cores of the domains have similar three
      dimensional structure. Remarkably, the similar geometry of the cores is
      stabilized by a different set of interactions involving distinct auxiliary
      elements.

PMID- 15459390
TI  - Interstitial collagenase is a Brownian ratchet driven by proteolysis of collagen.
AB  - We show that activated collagenase (MMP-1) moves processively on the collagen
      fibril. The mechanism of movement is a biased diffusion with the bias component
      dependent on the proteolysis of its substrate, not adenosine triphosphate (ATP)
      hydrolysis. Inactivation of the enzyme by a single amino acid residue
      substitution in the active center eliminates the bias without noticeable effect
      on rate of diffusion. Monte Carlo simulations using a model similar to a "burnt
      bridge" Brownian ratchet accurately describe our experimental results and
      previous observations on kinetics of collagen digestion. The biological
      implications of MMP-1 acting as a molecular ratchet tethered to the cell surface
      suggest new mechanisms for its role in tissue remodeling and cell-matrix
      interaction.

PMID- 15459391
TI  - Life history trade-offs assemble ecological guilds.
AB  - Ecological theory predicts that competition for a limiting resource will lead to
      the exclusion of species unless the within-species effects outweigh the between
      species effects. Understanding how multiple competitors might coexist on a single
      resource has focused on the prescriptive formalism of a necessary niche width and
      limiting similarity. Here, we show how continuously varying life histories and
      trade-offs in these characteristics can allow multiple competitors to coexist,
      and we reveal how limiting similarity emerges and is shaped by the ecological and
      evolutionary characteristics of competitors. In this way, we illustrate how the
      interplay of ecological and evolutionary processes acts to shape ecological
      communities in a unique way. This leads us to argue that evolutionary processes
      (life-history trait trade-offs) are fundamental to the understanding of the
      structure of ecological communities.

PMID- 15459392
TI  - Zebrafish Dpr2 inhibits mesoderm induction by promoting degradation of nodal
      receptors.
AB  - Nodal proteins, members of the transforming growth factor-beta (TGFbeta)
      superfamily, have been identified as key endogenous mesoderm inducers in
      vertebrates. Precise control of Nodal signaling is essential for normal
      development of embryos. Here, we report that zebrafish dapper2 (dpr2) is
      expressed in mesoderm precursors during early embryogenesis and is positively
      regulated by Nodal signals. In vivo functional studies in zebrafish suggest that
      Dpr2 suppresses mesoderm induction activities of Nodal signaling. Dpr2 is
      localized in late endosomes, binds to the TGFbeta receptors ALK5 and ALK4, and
      accelerates lysosomal degradation of these receptors.

PMID- 15459393
TI  - Ubistatins inhibit proteasome-dependent degradation by binding the ubiquitin
      chain.
AB  - To identify previously unknown small molecules that inhibit cell cycle machinery,
      we performed a chemical genetic screen in Xenopus extracts. One class of
      inhibitors, termed ubistatins, blocked cell cycle progression by inhibiting
      cyclin B proteolysis and inhibited degradation of ubiquitinated Sic1 by purified
      proteasomes. Ubistatins blocked the binding of ubiquitinated substrates to the
      proteasome by targeting the ubiquitin-ubiquitin interface of Lys(48)-linked
      chains. The same interface is recognized by ubiquitin-chain receptors of the
      proteasome, indicating that ubistatins act by disrupting a critical protein
      protein interaction in the ubiquitin-proteasome system.

PMID- 15459394
TI  - Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis.
AB  - The Golgi enzyme beta1,6 N-acetylglucosaminyltransferase V (Mgat5) is up
      regulated in carcinomas and promotes the substitution of N-glycan with poly N
      acetyllactosamine, the preferred ligand for galectin-3 (Gal-3). Here, we report
      that expression of Mgat5 sensitized mouse cells to multiple cytokines. Gal-3
      cross-linked Mgat5-modified N-glycans on epidermal growth factor and transforming
      growth factor-beta receptors at the cell surface and delayed their removal by
      constitutive endocytosis. Mgat5 expression in mammary carcinoma was rate limiting
      for cytokine signaling and consequently for epithelial-mesenchymal transition,
      cell motility, and tumor metastasis. Mgat5 also promoted cytokine-mediated
      leukocyte signaling, phagocytosis, and extravasation in vivo. Thus, conditional
      regulation of N-glycan processing drives synchronous modification of cytokine
      receptors, which balances their surface retention against loss via endocytosis.

PMID- 15459395
TI  - Nonvisual photoreception in the chick iris.
AB  - The embryonic chicken iris constricts to light ex vivo, but with characteristics
      atypical of visual phototransduction. The chick iris was most sensitive to short
      wavelength light, demonstrating an action spectrum consistent with cryptochrome
      rather than with opsin pigments. Pupillary responses did not attenuate after
      saturating light exposure, but showed paradoxical potentiation. Iris
      photosensitivity was not affected by retinoid depletion or inhibitors of visual
      phototransduction. Knockdown of cryptochrome expression, but not of melanopsin
      expression, decreased iris photosensitivity. These data characterize a non-opsin
      photoreception mechanism in a vertebrate eye and suggest a conserved
      photoreceptive role for cryptochromes in vertebrates.

PMID- 15459396
TI  - BASHH guideline for gonorrhoea.

PMID- 15459397
TI  - National chlamydia screening programme in England: making progress.

PMID- 15459398
TI  - Current status of syndromic management of sexually transmitted infections in
      developing countries.

PMID- 15459399
TI  - Establishing the National Chlamydia Screening Programme in England: results from
      the first full year of screening.
AB  - BACKGROUND: The phased implementation of the National Chlamydia Screening
      Programme (NCSP) began in September 2002. The NCSP offers opportunistic screening
      for chlamydia to women and men under 25 years of age attending clinical and non
      clinical screening venues using non-invasive urine or vulvo-vaginal swab samples
      tested via nucleic acid amplification. This review describes the implementation
      of the NCSP, reports positivity rates for the first year, and explores risk
      factors for genital chlamydial infection. METHODS: Cross sectional study of the
      first year's screening data from the NCSP. A standardised core dataset for each
      screening test was collected from 302 screening venues, excluding genitourinary
      medicine (GUM) clinics, across 10 phase 1 programme areas. We estimated chlamydia
      positivity by demographic and behavioural characteristics, and investigated
      factors associated with infection through univariate and multivariate analyses.
      RESULTS: Chlamydia positivity among people under 25 years of age screened in non
      GUM settings was 10.1% (1538/15 241) in women and 13.3% (156/1172) in men. Risk
      factors varied by sex: for women-age 16-19, non-white ethnicity, and sexual
      behaviours were associated with infection; for men-only age 20-24 and non-white
      ethnicity were associated with infection. DISCUSSION: In the first phase of the
      NCSP, 16 413 opportunistic screens among young adults under 25 years of age were
      performed at non-GUM settings and testing volume increased over time. Rates of
      disease were similar to those found during the English screening pilot and were
      comparable to the first year of widespread screening in Sweden and the United
      States. The screening programme in England will continue to expand as further
      phases are included, with national coverage anticipated by 2008.

PMID- 15459400
TI  - The chlamydia screening studies: rationale and design.
AB  - BACKGROUND: Screening has been recommended to reduce the prevalence and morbidity
      associated with genital chlamydia infection in the United Kingdom. METHODS: We
      describe the rationale and study design of the Chlamydia Screening Studies
      (ClaSS), a collaborative project designed to evaluate screening outside
      genitourinary medicine clinics. A non-selective, active screening approach in 16
      39 year olds randomly sampled from 27 general practice lists in the Bristol and
      Birmingham areas formed the basis of interlinked studies: a case-control study
      was used to investigate factors to improve the targeting of screening;
      participants with chlamydia were invited to enroll in a randomised controlled
      trial to evaluate partner notification conducted in primary care; and laboratory
      based studies were used to assess the best specimens and tests. We also explored
      psychosocial effects of screening and partner notification and modelled the cost
      effectiveness of the programme. CONCLUSION: Results from four pilot practices
      show that mailing of specimens for chlamydia testing is feasible but that it is
      difficult to achieve high response rates with postal screening. The high
      prevalence of asymptomatic infection in men suggests that efforts to screen men
      for chlamydia should be strengthened.

PMID- 15459401
TI  - Chlamydia trachomatis prevalence in men in the mid-west of Ireland.
AB  - OBJECTIVES: To estimate the prevalence of chlamydia infection in young men in the
      Mid-Western Health Board Region of Ireland, and to determine risk factors for its
      acquisition. METHODS: Consecutive men attending orthopaedic clinics (OPD), and a
      university sports arena (UL) were recruited to a chlamydia prevalence study. All
      men aged 17-35 who had been sexually active and had not passed urine in the last
      hour were eligible. Information about chlamydia was given, informed consent
      obtained, and a self administered questionnaire was completed. A first void urine
      (FVU) was collected and tested by ligase chain reaction (LCR). RESULTS: 82%
      (207/252) of men from OPD, and 60% (186/310) from UL participated. 6.3% (13/207)
      from the OPD and 5.4% (10/186) from UL tested LCR positive, giving an overall
      prevalence of 5.9% (23/393). Proved risk factors for chlamydial positivity were:
      (1) more than one sexual partner in previous 6 months, (2) more than eight
      lifetime sexual partners, (3) current symptoms (dysuria or discharge). No
      statistical significance was found for age, condom use, smoking, days since last
      sexual intercourse and previous GUM clinic attendance. No statistically
      significant difference to cost effective prevalence of 6% was shown. CONCLUSIONS:
      A 5.9% prevalence of Chlamydia trachomatis was found which is cost effective to
      screen and treat. Non-invasive screening of men in the community was possible.
      Numbers of sexual partners and current symptoms were significant risk factors.
      Since only 25% of men in this laboratory were diagnosed with chlamydia outside
      the GUM clinic, compared with 59% of women, it is important that community
      screening of men is promoted.

PMID- 15459402
TI  - Chlamydia trachomatis in the United Kingdom: a systematic review and analysis of
      prevalence studies.
AB  - OBJECTIVES: To undertake a systematic review to obtain estimates of genital
      Chlamydia trachomatis prevalence in various populations in the United Kingdom and
      Ireland; to determine which populations have the highest rates of infection; and
      to explore the most important determinants of infection. METHODS: Electronic
      databases were searched using the keywords "chlamydia" and "England," "Wales,"
      "UK," "Scotland," "Ireland," or "Britain." Additional unpublished data and
      references were solicited from experts. Studies were included in the analysis if
      C trachomatis prevalence was reported, and if they met inclusion criteria. Nine
      variables identified as potentially important descriptors of chlamydia prevalence
      were extracted from each study and analysed using various logistic regression
      models. Only studies reporting prevalence in female populations were included in
      the models, because there were few data from males. RESULTS: 357 studies were
      identified using the search methods, 90 of which met inclusion criteria, and 19
      of which contributed to the final model. The most influential variables on
      prevalence were age and setting of the population tested. In general practice
      surgeries, the under 20 year old age group had an estimated prevalence of 8.1%
      (95% CI 6.5 to 9.9), 20-24 year olds 5.2% (95% CI 4.3 to 6.3), 25-29 year olds
      2.6% (95% CI 2.0 to 3.3), decreasing to 1.4% (95% CI 1.0 to 1.9) in those aged
      over 30 years. Overall, healthcare settings had higher prevalence estimates than
      population based studies. For example, among under 20 year olds, estimates were
      17.3% (95% CI 13.6 to 21.8) in genitourinary medicine clinics, 12.6% (95% CI 6.4
      to 23.2) in antenatal clinics, 12.3% (95% CI 9.8 to 15.3) in termination of
      pregnancy clinics, 10.7% (95% CI 8.3 to 13.8) in youth clinics, 10.0% (95% CI 8.7
      to 11.5) in family planning clinics, and 8.1% (95% CI 6.5 to 9.9) in general
      practice, compared to 5.0% (95% CI 3.2 to 7.6) in population based studies. The
      type of test, specimen used, date, and location of test were not strongly
      associated with chlamydia prevalence. CONCLUSION: The chlamydia prevalence
      estimates by age and setting from the model may be used to inform chlamydia
      screening strategies. The systematic review revealed much heterogeneity in the
      studies identified, but with clear patterns of prevalence. It also indicated gaps
      in the knowledge about chlamydia prevalence in certain subgroups such as men and
      the general population.

PMID- 15459403
TI  - Modelling the healthcare costs of an opportunistic chlamydia screening programme.
AB  - OBJECTIVES: To estimate the average cost per screening offer, cost per testing
      episode and cost per chlamydia positive episode for an opportunistic chlamydia
      screening programme (including partner management), and to explore the
      uncertainty of parameter assumptions, based on the costs to the healthcare
      system. METHODS: A decision tree was constructed and parameterised using
      empirical data from a chlamydia screening pilot study and other sources. The
      model was run using baseline data from the pilot, and univariate and multivariate
      sensitivity analyses were conducted. RESULTS: The total estimated cost for
      offering screening over 12 months to 33,215 females aged 16-24 was 493,412 pounds
      . The average cost (with partner management) was 14.88 pounds per screening offer
      (90% credibility interval (CI) 10.34 to 18.56), 21.83 pounds per testing episode
      (90% CI 18.16 to 24.20), and 38.36 pounds per positive episode (90% CI 33.97 to
      42.25). The proportion of individuals accepting screening, the clinician (general
      practitioner/nurse) time and their relative involvement in discussing screening,
      the test cost, the time to notify patients of their results, and the receptionist
      time recruiting patients had the greatest impact on the outcomes in both the
      univariate and multivariate sensitivity analyses. CONCLUSIONS: Results from this
      costing study may be used to inform resource allocation for current and future
      chlamydia screening programme implementation.

PMID- 15459404
TI  - Liquid based cytology: examination of its potential in a chlamydia screening
      programme.
AB  - OBJECTIVE: To assess the feasibility of testing for chlamydia directly on a
      single liquid based specimen (ThinPrep test) collected for cervical screening.
      METHOD: Cervical smears were taken using a Cervex spatula and rinsed in the
      liquid based cytology collection vial. Following this, the conventional sample
      for chlamydia testing was taken from the endocervix using an Abbott Collection
      kit. Cytological specimens were prepared using an automated slide processor.
      Residual cellular material and the conventional samples were sent to the
      laboratory where both were tested for chlamydia by ligase chain reaction (LCR).
      The manufacturer's protocol for LCR urine testing was modified to substitute 1 ml
      of PreservCyt suspension. RESULTS: 581 women had both swab and cytology
      suspension tested for Chlamydia trachomatis with LCR. There were 19 concordant
      positive and 562 concordant negative reports. The stability of chlamydia in the
      cytology suspension was maintained for at least 5 months. CONCLUSION: The
      findings lead us to conclude that samples collected for liquid based cytology
      using the ThinPrep test collection vial provide a potential platform for
      chlamydia screening, though the study established several issues to be addressed
      to make this a practical proposition.

PMID- 15459405
TI  - Declining prevalence of STI in the London sex industry, 1985 to 2002.
AB  - OBJECTIVES: To describe major changes in the London sex industry between 1985 and
      2002 and assess the implications for sexually transmitted infection (STI) risk.
      METHOD: A descriptive study comparing women who first attended a sex work clinic
      between 1996 and 2002 and those first attending from 1985 to 1992; a nested case
      control study. 1050 female sex workers took part. The setting was a specialist
      clinical service for sex workers based in a London genitourinary medicine (GUM)
      clinic, and fieldwork in west London. The main outcome measures were reported
      condom use and prevalent STI. RESULTS: Over the period of the study there was a
      significant increase in the proportion of sex workers not born in the United
      Kingdom (from 25% to 63%, p < 0.001), and women entered sex work at an older age
      (median 24 years compared with 20 years, p < 0.001). Condom use increased (with
      the exception of oral sex). There was a significant decline in the proportion of
      participants reporting a previous STI (32% compared with 80%, p < 0.001) and the
      prevalence of acute STI declined from 25% to 8% (p < 0.001). Acute STI was
      associated with younger age, younger age at first sex work, being new to sex
      work, and inconsistent condom use. In a multivariate analysis unprotected sex
      with clients was the only significant risk. CONCLUSION: Major restructuring of
      the sex industry, including the shift to a primarily migrant workforce, has been
      associated with a steep decline in acute STI, undermining popular assumptions
      that migrant sex workers are central to the ongoing STI epidemic. We attribute
      the decline in acute STI to an increase in safer sex.

PMID- 15459406
TI  - Investigating ethnic inequalities in the incidence of sexually transmitted
      infections: mathematical modelling study.
AB  - OBJECTIVES: To investigate ethnic differences in rates of gonorrhoea using
      empirical sexual behaviour data in a simple mathematical model. To explore the
      impact of different intervention strategies in this simulated population.
      METHODS: The findings from cross sectional studies of gonorrhoea rates and sexual
      behaviour in three ethnic groups in south east London were used to determine the
      parameters for a deterministic, mathematical model of gonorrhoea transmission
      dynamics, in a population stratified by sex, sexual activity (rate of partner
      change), and ethnic group (white, black African, and black Caribbean). We
      compared predicted and observed rates of infection and simulated the effects of
      targeted and population-wide intervention strategies. RESULTS: In model
      simulations the reported sexual behaviours and mixing patterns generated major
      differences in the rates of gonorrhoea experienced by each subpopulation. The fit
      of the model to observed data was sensitive to assumptions about the degree of
      mixing by level of sexual activity, the numbers of sexual partnerships reported
      by men and women, and the degree to which observed data underestimate female
      infection rates. Interventions to reduce duration of infection were most
      effective when targeted at black Caribbeans. CONCLUSIONS: Average measures of
      sexual behaviour in large populations are inadequate descriptors for the
      epidemiology of gonorrhoea. The consistency between the model results and
      empirical data shows that profound differences in gonorrhoea rates between ethnic
      groups can be explained by modest differences in a limited number of sexual
      behaviours and mixing patterns. Targeting effective services to particular ethnic
      groups can have a disproportionate influence on disease reduction in the whole
      community.

PMID- 15459407
TI  - Which cephalosporin for gonorrhoea?
AB  - The recommended treatment for gonorrhoea in the United Kingdom has, until
      recently, included the fluoroquinolone, ciprofloxacin, which consequently was
      used by most genitourinary medicine clinics. In 2002 national surveillance data
      showed that resistance to ciprofloxacin had risen to a prevalence of 9.8% (9% in
      2003), indicating that the target of >95% efficacy in first line therapy was no
      longer achievable. The third generation cephalosporins, ceftriaxone
      (intramuscular) or cefixime (oral), are the recommended alternatives, but recent
      audit data reveal other cephalosporins are currently being used to treat
      gonorrhoea, notably including cefuroxime (intramuscular or, often, oral). A
      pharmacodynamic analysis was undertaken to determine whether all these regimens
      were equally potent. Ceftriaxone, 250 (or 500) mg intramuscularly, or cefixime,
      400 mg orally, were calculated to give free drug concentrations above the MIC90
      for 22-50 hours post dose whereas the cefuroxime regimens being used were
      pharmacodynamically borderline, achieving this target for only 6.8-11.2 hours and
      raising the spectre that continued use may select for stepwise increases in
      resistance, as occurred with penicillin. We therefore underscore that ceftriaxone
      or cefixime should be the agents of choice to replace ciprofloxacin, as
      recommended in the new treatment guidelines, and that cefuroxime is a poor
      substitute.

PMID- 15459408
TI  - Current practice of sexual history taking by sexual health physicians in
      Australia and New Zealand.
AB  - OBJECTIVES: To document the current practice of fellows of the Australasian
      College of Sexual Health Physicians (ACSHP) when taking a sexual history from a
      new client. METHOD: A postal questionnaire was sent to all eligible fellows
      practising sexual health medicine in public sexual health centres in Australia
      and New Zealand (n = 93). The study period extended from 3 February to 4 April
      2003 inclusive. RESULTS: 77 (83%) fellows returned the questionnaire and, of
      these, 71 (76%) were eligible for inclusion in the analysis. The median number of
      years of practising sexual health medicine was 16 (range 5-32) with 70% having
      worked in the field for 10 years or more. The generic questions that fellows
      asked most often concerned the presenting complaint/reason for attendance, the
      history of the presenting complaint, current sexual relationship status and last
      sexual contact, history of sexually transmitted infections (STIs), use of condoms
      during sexual intercourse in the past 3 months, and pattern (always, usually,
      sometimes, never) of condom use during that time period. The least frequently
      asked generic questions concerned age at first sexual activity, the number of
      sexual contacts, lifetime condom use, and hepatitis A status. CONCLUSION: This
      study establishes the consistency and variability of sexual health information
      currently collected by fellows of the ACSHP when taking a history from a new
      client.

PMID- 15459409
TI  - Risk factors associated with failure of syndromic treatment of sexually
      transmitted diseases among women seeking primary care in Addis Ababa.
AB  - OBJECTIVE: To determine risk factors associated with the failure of syndromic
      management of sexually transmitted diseases (STDs) among women seeking treatment
      in primary healthcare centre in Addis Ababa, Ethiopia. METHODS: Women with
      symptomatic STDs seeking care in a health centre were prospectively enrolled. A
      total of 259 women were interviewed and underwent clinical examination; 106 were
      enrolled and received syndromic STD treatment and 91% returned for follow up.
      Logistic regression analysis was used to identify risk factors associated with
      treatment failure. RESULTS: Of the 106 women enrolled and presenting with
      symptomatic STDs 67% were HIV seropositive. Syndromic STD treatment did not
      result in clinical improvement in 30% of the women. Having genital ulcer disease,
      genital ulcer disease with genital discharge, genital warts, bacterial vaginosis
      and plasma HIV-1 load >10,000 copies RNA/ml or being HIV seropositive were all
      significantly associated with treatment failure. In multivariate analysis,
      however, only genital ulcer disease was significantly associated with treatment
      failure. CONCLUSION: In our setting, the association between HIV and genital
      ulcer disease caused by herpes may, therefore, be the reason for the failure of
      treatment.

PMID- 15459410
TI  - Chlamydia and gonorrhoea in pregnancy: effectiveness of diagnosis and treatment
      in Botswana.
AB  - BACKGROUND: Millions of patients are prescribed drugs for sexually transmitted
      infections (STIs) in developing countries each year, yet the treatment effect of
      these prescriptions is largely unknown. OBJECTIVES: To determine if the
      prescribing of erythromycin and ceftriaxone to pregnant women with STI symptoms
      leads to a reduction in the prevalence among these women of chlamydia and
      gonorrhoea, respectively. METHODS: We compared the prevalence of chlamydia among
      116 pregnant women who had been prescribed erythromycin for a history of STI
      symptoms in their current pregnancy with the prevalence in a control group of 557
      pregnant women who had not been prescribed this drug. Similarly we compared the
      prevalence of gonorrhoea among 110 pregnant women who had and 561 women who had
      not been prescribed ceftriaxone. RESULTS: There was no significant difference in
      the prevalence of chlamydia among the women who had and the women who had not
      been prescribed erythromycin four times daily for 10 days (7% v 8%). Contrarily,
      none of the women who had been prescribed a single dose of ceftriaxone had
      gonorrhoea, whereas 4% of the women who had not had this drug prescribed did have
      gonorrhoea. CONCLUSIONS: The prescribing of erythromycin seems to have had a
      limited effect on chlamydia in this population, whereas the prescribing of
      ceftriaxone led to the curing of gonorrhoea. Ceftriaxone is provided as a single
      dose injection at the point of care, and the differential effectiveness between
      the two drugs may reflect low compliance with the complex erythromycin regimen.
      Interventions to increase compliance could improve cure rates. The use of a
      simpler drug regimen should be considered when low compliance is likely.

PMID- 15459411
TI  - Vaginal leucocyte counts in women with bacterial vaginosis: relation to vaginal
      and cervical infections.
AB  - OBJECTIVES: To evaluate whether an elevated vaginal leucocyte count in women with
      bacterial vaginosis (BV) predicts the presence of vaginal or cervical infections,
      and to assess the relation of vaginal WBC counts to clinical manifestations.
      METHODS: We retrospectively analysed the relation of vaginal leucocyte counts to
      vaginal and cervical infections and to clinical manifestations in non-pregnant
      women diagnosed with BV at an STD clinic visit. RESULTS: Of 296 women with BV
      studied, the median age was 24 years and 81% were African-American. Elevated
      vaginal leucocyte counts were associated with objective signs of vaginitis and
      cervicitis and also predicted candidiasis (OR 7.9, 95% CI 2.2 to 28.9), chlamydia
      (OR 3.1, 95% CI 1.4 to 6.7), gonorrhoea (OR 2.7, 95% CI 1.3 to 5.4), or
      trichomoniasis (OR 3.4, 95% CI 1.6 to 7.3). In general, as a screening test for
      vaginal or cervical infections, vaginal leucocyte count had moderate
      sensitivities and specificities, low positive predictive values, and high
      negative predictive values. CONCLUSIONS: An elevated vaginal leucocyte count in
      women with BV was a strong predictor of vaginal or cervical infections. Vaginal
      leucocyte quantification may provide an alternative approach to assessing need
      for empirical therapy for chlamydia and gonorrhoea, particularly in resource
      limited high STD risk settings that provide syndromic management.

PMID- 15459412
TI  - Diagnosis of genital herpes by real time PCR in routine clinical practice.
AB  - BACKGROUND: Virus isolation in cell culture is the recognised diagnostic gold
      standard for genital herpes. Although increasing evidence indicates that
      polymerase chain reaction (PCR) provides a more rapid and sensitive diagnostic
      method, its implementation in routine diagnostic settings has been limited by
      concerns over contamination and cost. OBJECTIVE: To evaluate the feasibility of
      replacing virus culture with PCR for the diagnosis of genital herpes in settings
      serving large populations of genitourinary medicine (GUM) attendees. METHODS:
      Genital swabs collected from 233 consecutive GUM attendees with suspected genital
      herpes were tested in parallel by virus culture and automated real time PCR.
      Three specimen preparation methods were evaluated and the assay reliability was
      assessed by repeat testing, comparison with a commercially available assay, and
      herpes simplex virus (HSV) sequence analysis. Probe melting temperatures (Tm)
      were used to differentiate between HSV types without additional post-PCR steps.
      RESULTS: HSV was detected in 79/233 (34%) samples by virus culture and 132/233
      (57%) samples by PCR. PCR significantly increased HSV detection in both early (<
      5 days) and late (> or = 5 days) presentations and in both first and recurrent
      episodes. HSV detection and typing by PCR was achieved within less than 4 hours
      leading to a significant reduction in labour compared to virus culture. Most
      specimens (120/132, 91%) were typed as HSV-2. Results were highly reproducible.
      CONCLUSIONS: Real time PCR is a highly reproducible, rapid, and labour efficient
      method for HSV detection in genital swabs. Its implementation is feasible in
      routine diagnostic settings.

PMID- 15459413
TI  - Dark ground microscopy and treponemal serological tests in the diagnosis of early
      syphilis.
AB  - OBJECTIVES: To evaluate the use of dark ground microscopy (DGM) and treponemal
      serological tests in the diagnosis of primary (PS) and secondary (SS) syphilis.
      METHODS: A retrospective case note review of patients with early syphilis who
      attended our department between January 2001 and December 2002. Data were
      collected on demographics, results of treponemal serology and DGM. RESULTS: 50
      individuals had PS and 36 individuals had SS. DGM was performed in 31/50 (62%) of
      PS cases and this was positive in 97%. In 17 (34%) cases of PS, treponemal EIA
      was negative initially. DGM was performed on 13 of these, all of which were
      positive. Therefore, EIA had a sensitivity of 57% when compared to DGM. In 27
      patients where EIA-IgM was performed, this was positive in 22 (81%), of which 12
      were EIA negative on initial screening. All SS cases had positive EIA. DGM was
      performed in 19/36 (52%) of SS cases and was positive in 16/19--that is, a
      sensitivity of 84% when compared to EIA. The major reason why DGM was not
      performed in the cases of PS was that herpes was the presumed diagnosis and in SS
      the rash was attributed to other causes. CONCLUSIONS: DGM is a rapid and
      sensitive test while EIA takes time for results and is less sensitive in PS. EIA
      IgM is a useful adjunct in PS. DGM allows immediate diagnosis, treatment, and
      partner notification preventing further transmission. Genitourinary medicine
      clinics should have trained staff to perform DGM on all anogenital ulcers and
      suspected syphilitic lesions.

PMID- 15459414
TI  - The performance of microscopic cervicitis for the detection of chlamydial
      infection.

PMID- 15459415
TI  - Chlamydia trachomatis heat shock protein 60 (cHSP60) antibodies in women without
      and with tubal pathology using a new commercially available assay.

PMID- 15459416
TI  - The prevalence of excessive alcohol consumption and the acceptability of brief
      advice in a sexual health clinic: cross sectional survey.

PMID- 15459417
TI  - Resolution of lymphocytic interstitial pneumonitis in an HIV infected adult after
      treatment with HAART.

PMID- 15459418
TI  - Oral sex and gum disease.

PMID- 15459419
TI  - Acute urinary retention following self treatment of genital warts with imiquimod
      5% cream.

PMID- 15459420
TI  - Knowledge of post exposure prophylaxis (PEP) for HIV among general practitioners
      in northern Sydney.

PMID- 15459422
TI  - HIV in black Caribbeans.

PMID- 15459425
TI  - Bisphosphonates: preclinical review.
AB  - Bisphosphonates effectively inhibit osteoclast-mediated bone resorption and are
      integral in the treatment of benign and malignant bone diseases. The evolution of
      bisphosphonates over the past 30 years has led to the development of nitrogen
      containing bisphosphonates (N-BPs), which have a mechanism of action different
      from that of the nonnitrogen-containing bisphosphonates. Studies conducted over
      the past decade have elucidated the mechanism of action and pharmacologic
      properties of the N-BPs. N-BPs exert their effects on osteoclasts and tumor cells
      by inhibiting a key enzyme in the mevalonate pathway, farnesyl diphosphate
      synthase, thus preventing protein prenylation and activation of intracellular
      signaling proteins such as Ras. Recent evidence suggests that N-BPs also induce
      production of a unique adenosine triphosphate analogue (Apppi) that can directly
      induce apoptosis. Our increased understanding of the pharmacologic effects of
      bisphosphonates is shedding light on the mechanisms by which they exert antitumor
      effects. As a result of their biochemical effects on protein prenylation, N-BPs
      induce caspase-dependent apoptosis, inhibit matrix metalloproteinase activity,
      and downregulate alpha(v)beta(3) and alpha(v)beta(5) integrins. In addition,
      zoledronic acid (Zometa; Novartis Pharmaceuticals Corp.; East Hanover, NJ and
      Basel, Switzerland) exerts synergistic antitumor activity when combined with
      other anticancer agents. Zoledronic acid also inhibits tumor cell adhesion to the
      extracellular matrix and invasion through Matrigel trade mark and has
      antiangiogenic activity. A growing body of evidence from animal models
      demonstrates that zoledronic acid and other bisphosphonates can reduce skeletal
      tumor burden and prevent metastasis to bone. Further studies are needed to fully
      elucidate these biochemical mechanisms and to determine if the antitumor
      potential of bisphosphonates translates to the clinical setting.

PMID- 15459426
TI  - Bisphosphonates: clinical experience.
AB  - Bone is a preferred site of metastasis for many solid tumors, and the
      complications associated with bone metastases can result in significant skeletal
      morbidity including severe bone pain, pathologic fracture, spinal cord
      compression, and hypercalcemia of malignancy (HCM). Bisphosphonates are the
      current standard of care for preventing skeletal complications associated with
      bone metastases. Clinical trials investigating the benefit of bisphosphonate
      therapy have used a composite end point defined as a skeletal-related event (SRE)
      or bone event, which typically includes pathologic fracture, spinal cord
      compression, radiation or surgery to bone, and HCM. Bisphosphonates have been
      shown to significantly reduce the incidence of these events in patients with bone
      metastases. Zoledronic acid (Zometa; Novartis Pharmaceuticals Corp.; East
      Hanover, NJ), pamidronate (Aredia; Novartis Pharmaceuticals Corp.), clodronate
      (Bonefos; Anthra Pharmaceuticals; Princeton, NJ), and ibandronate (Bondronat;
      Hoffmann-La Roche Inc.; Nutley, NJ) all have demonstrated efficacy superior to
      that of placebo in patients with breast cancer. Zoledronic acid is the only
      bisphosphonate that has been compared directly with pamidronate, and it was shown
      by multiple event analysis to be significantly more effective at reducing the
      risk of an SRE. In patients with prostate cancer, clodronate, etidronate
      (Didronel; Procter and Gamble Pharmaceuticals, Inc.; Cincinnati, OH), and
      pamidronate have demonstrated transient palliation of bone pain. However,
      zoledronic acid is the only bisphosphonate to demonstrate both significant and
      sustained pain reduction and a significantly lower incidence and longer time to
      onset of SREs compared with placebo. Zoledronic acid is also the only
      bisphosphonate to demonstrate efficacy in patients with bone metastases from a
      variety of other solid tumors, including lung cancer and renal cell carcinoma. In
      conclusion, bisphosphonates effectively reduce skeletal complications in patients
      with bone metastases from breast cancer, and zoledronic acid has demonstrated the
      broadest clinical activity in patients with a wide variety of tumor types.

PMID- 15459427
TI  - Safety of intravenous and oral bisphosphonates and compliance with dosing
      regimens.
AB  - Patients with advanced cancers--particularly breast and prostate cancers--are at
      high risk for bone metastasis, leading to accelerated bone resorption and
      clinically significant skeletal morbidity. Bisphosphonates are effective
      inhibitors of bone resorption and reduce the risk of skeletal complications in
      patients with bone metastases. The standard routes of administration for
      bisphosphonates used in clinical practice are either oral or i.v. infusion. Oral
      administration of bisphosphonates is complicated by poor bioavailability
      (generally <5%) and poor gastrointestinal tolerability. First-generation
      bisphosphonates, such as clodronate (Bonefos; Anthra Pharmaceuticals; Princeton,
      NJ), must be administered at high oral doses (1,600-3,200 mg/day) to achieve
      therapeutic effects, which leads to poor tolerability and compliance with oral
      dosing regimens. Infusion of bisphosphonates is associated with dose- and
      infusion-rate-dependent effects on renal function. In particular, high
      bisphosphonate doses (e.g., 1,500 mg clodronate) can cause severe renal toxicity
      unless infused slowly over many hours. In contrast, the newer, more potent
      bisphosphonates effectively inhibit bone resorption at micromolar concentrations,
      and the small doses required can be administered via relatively short i.v.
      infusions without adversely affecting renal function. Zoledronic acid (Zometa;
      Novartis Pharmaceuticals Corp.; East Hanover, NJ) is a new generation
      bisphosphonate, and the recommended dose of 4 mg can be safely infused over 15
      minutes. The 90-mg dose of pamidronate (Aredia; Novartis Pharmaceuticals Corp.)
      and the 6-mg dose of ibandronate (Bondronat; Hoffmann-La Roche Inc.; Nutley, NJ)
      require 1- to 4-hour infusions. Intravenous bisphosphonates require less frequent
      dosing (once a month) and are generally well tolerated with long-term use in
      patients with bone metastases. Zoledronic acid has demonstrated the broadest
      clinical activity in patients with bone metastases.

PMID- 15459428
TI  - Toward new horizons: the future of bisphosphonate therapy.
AB  - Bisphosphonate therapy has become a standard of care for patients with malignant
      bone disease. In addition, preclinical and preliminary clinical data suggest that
      bisphosphonates may prevent cancer-treatment-induced bone loss (CTIBL) and the
      development of malignant bone disease in patients with early-stage cancer.
      Patients who receive adjuvant hormonal therapy for breast cancer or androgen
      deprivation therapy for prostate cancer are at an especially high risk for CTIBL
      because of reduced estrogenic signaling. Oral clodronate (Bonefos; Anthra
      Pharmaceuticals; Princeton, NJ), oral risedronate (Actonel; Proctor and Gamble
      Pharmaceuticals, Inc.; Cincinnati, OH), and i.v. zoledronic acid (Zometa;
      Novartis Pharmaceuticals Corp.; East Hanover, NJ) have all demonstrated promise
      in preventing CTIBL in patients receiving hormonal therapy for breast cancer.
      Zoledronic acid has demonstrated efficacy with the longest between-treatment
      interval (3-6 months) and is currently being investigated in the Zometa/Femara
      Adjuvant Synergy Trials (Z-FAST and ZO-FAST in the United States and Europe,
      respectively). In patients receiving androgen-deprivation therapy for prostate
      cancer, i.v. pamidronate (Aredia; Novartis Pharmaceuticals Corp.) and i.v.
      zoledronic acid both have demonstrated significant benefits over placebo, but
      only zoledronic acid produced significant increases in bone mineral density
      compared with baseline values. Additionally, bisphosphonates have demonstrated
      antitumor activities in preclinical models, and clinical trials with oral
      clodronate suggest that bisphosphonates might prevent or delay bone metastasis in
      patients with early-stage breast cancer. Clinical trials are investigating the
      effect of zoledronic acid on disease progression in patients with breast cancer,
      prostate cancer, and non-small cell lung cancer. The results of these clinical
      trials should further define the clinical benefit of bisphosphonates in the
      oncology setting.

PMID- 15459429
TI  - Proceedings of the Princeton Conference on Cerebrovascular Disease. April 2-4,
      2004, Baltimore, Maryland, USA.

PMID- 15459430
TI  - Genomics of preconditioning.
AB  - Brief episodes of ischemia can protect against subsequent damaging ischemic
      events; however, the molecular mechanisms responsible for protection are poorly
      understood. Identifying genes involved in this process could provide insight into
      cell survival and treatment of stroke. We developed a murine model of ischemic
      preconditioning and subsequent stroke and used gene expression profiling to
      identify genes that may be involved in neuroprotective pathways. Middle cerebral
      artery occlusions were performed in mice for 15 minutes. (preconditioning), 60
      minutes (stroke), or 15 minutes, followed 72 hours later with 60 minutes
      (preconditioning plus stroke) of middle cerebral artery occlusions. RNA from a
      region of cortex that is protected by ischemic preconditioning was hybridized to
      oligonucleotide microarrays. Follow-up experiments used patch clamp to examine
      cell conductance in cultured neurons exposed to oxygen-glucose deprivation.
      Stroke, ischemic preconditioning, and ischemic preconditioning plus stroke all
      induced gene changes that overlapped little among conditions. Stroke induced
      robust upregulation of gene expression whereas preconditioning followed by stroke
      resulted in a marked downregulation. Genes upregulated by stroke suggested
      activation of stress/inflammatory pathways and increased metabolism and ion
      channel function. Preconditioning tended to decrease genes involved in these
      pathways. Follow-up experiments show that preconditioning decreased voltage-gated
      potassium currents in vitro and increased bleeding time. Preconditioning
      reprograms the response to ischemic injury via transcriptional changes that may
      suppress metabolic pathways and immune responses, reduce ion channel activity,
      and decrease blood coagulation. These changes resemble evolutionarily conserved
      responses to decreased blood flow and oxygen availability that occur during
      hibernation.

PMID- 15459431
TI  - Immediate computed tomography scanning of acute stroke is cost-effective and
      improves quality of life.
AB  - BACKGROUND AND PURPOSE: Stroke is very common, but computed tomography (CT)
      scanning, an expensive and finite resource, is required to differentiate cerebral
      infarction, hemorrhage, and stroke mimics. We determined whether, and in what
      circumstances, CT is cost-effective in acute stroke. METHODS: We developed a
      decision tree representing acute stroke care pathways populated with data from
      multiple sources. We determined the effect of diagnostic information from CT
      scanning on functional outcome, length of stay, costs, and quality of life during
      5 years for 13 alternative CT strategies (varying proportions and types of
      patients and rapidity of scanning). RESULTS: For 1000 patients aged 70 to 74
      years, the policy "scan all strokes within 48 hours" cost 10,279,728 pounds
      sterling and achieved 1982.3 quality-adjusted life years (QALYs). The most cost
      effective strategy was "scan all immediately" (9,993,676 pounds sterling and
      1982.4 QALYs). The least cost-effective was "scan patients on anticoagulants and
      those in a life-threatening condition immediately and the rest within 14 days"
      (12,592,666 pounds sterling and 1931.8 QALYs). "Scan no patients" reduced QALYs
      (1904.2) and increased cost (10,544,000 pounds sterling). CONCLUSIONS: Immediate
      CT scanning is the most cost-effective strategy. For the majority of acute stroke
      patients, increasing independent survival by correct early diagnosis, ensuring
      appropriate subsequent treatment and management decisions, reduced costs of
      stroke and increased QALYs.

PMID- 15459432
TI  - RAGE (yin) versus LRP (yang) balance regulates alzheimer amyloid beta-peptide
      clearance through transport across the blood-brain barrier.
AB  - Accumulation of amyloid beta-peptide (Abeta) in the central nervous system (CNS)
      may initiate pathogenic cascades mediating neurovascular and neuronal
      dysfunctions associated with the development of cerebral beta-amyloidosis and
      cognitive decline in patients with Alzheimer disease (AD) and with related
      familial cerebrovascular disorders. Whether Abeta-related pathology in the CNS is
      reversible or not and what key therapeutic targets are controlling Abeta/amyloid
      levels in the aging brain remain debatable. In this article, we summarize recent
      evidence why the receptor for advanced glycation end products and low-density
      lipoprotein receptor related protein 1 in the vascular CNS barriers are critical
      for regulation of Abeta homeostasis in the CNS and how altered activities in
      these 2 receptors at the blood-brain barrier may contribute to the CNS Abeta
      accumulation resulting in neuroinflammation, disconnect between the cerebral
      blood flow and metabolism, altered synaptic transmission, neuronal injury, and
      amyloid deposition into parenchymal and neurovascular lesions. We briefly discuss
      the potential of advanced glycation end products and low-density lipoprotein
      receptor related protein 1-based therapeutic strategies to control brain Abeta in
      animal models of AD and ultimately in patients with AD and related familial
      cerebrovascular beta-amyloidoses.

PMID- 15459433
TI  - Identifying thresholds for penumbra and irreversible tissue damage.
AB  - Diffusion-weighted MRI (DWI) in combination with perfusion-weighted MRI (PWI) has
      become a widely accepted modality for the selection of patients amenable for
      acute therapy, if a mismatch between these procedures suggests viable penumbral
      tissue. However, DWI as well as PWI yields semiquantitative measures limiting the
      definitions of irreversible damage and of potentially viable penumbral tissue.
      These limitations of PWI/DWI may be better understood if findings in individual
      patients are compared with the results from measurements of blood flow, oxygen
      metabolism, and benzodiazepine receptor binding obtained with positron emission
      tomography (PET). Comparative studies with PET and MRI were performed in 3 groups
      of patients: (1) In 12 acute stroke patients, results from DWI (median, 6.5 hours
      after symptom onset) and 11C-flumazenil (FMZ) PET (median, 85 minutes between DWI
      and PET) were compared with infarct extension 24 to 48 hours later on T2-weighted
      MRI. (2) In 11 acute stroke patients, results from PWI (median, 8 hours after
      symptom onset) were compared with cerebral blood flow measurements obtained with
      [15O]H2O PET (interval, 60 minutes between PWI and PET). (3) In 10 patients with
      acute (n=5) or chronic stroke (n=5), results from PWI/DWI were compared with PET
      of cerebral blood flow and oxygen consumption to detect mismatch or increased
      oxygen extraction fraction as surrogate markers of penumbra. Results were: (1)
      from regions with increased DWI intensity, decreased apparent diffusion
      coefficient (ADC) and decreased FMZ binding probability curves were computed for
      eventual infarction, and 95% prediction limits were determined. These limits
      predicted 83.5% (FMZ), 84.7% (DWI), and 70.9% (ADC) of the final infarct volume.
      However, the false-positive predictions were much higher for the DWI variables
      (5.1 and 3.6 cm3 for DWI and ADC versus a median of 0 for FMZ). (2) The
      comparison of volumes generated by different time to peak (TTP) thresholds (PWI)
      and hypoperfusion <20 mL/100 g per minute (PET) indicates that a TTP delay of 4
      to 6 seconds yields a fair estimate of hypoperfusion. (3) The PWI/DWI mismatch
      with TTP >4 seconds did not reliably correspond to the penumbra as assessed by
      PET (oxygen extraction fraction >150%). Only 6 of 10 patients with a mismatch had
      areas of penumbra. In these cases, the penumbra volume was overestimated by MRI.
      DWI correlates with FMZ results and, with a few exceptions, yields a good
      estimate of acute tissue damage and final infarct volume. PWI measures seem to be
      less reliable; the TTP prolongation of >4 seconds assessed only 83% of the volume
      of hypoperfusion <20 mL/100 g per minute. The mismatch volume imprecisely depicts
      increased oxygen extraction fraction, and, despite its clinical role for
      selection of patients for eventual therapy, it does not to seem to be a reliable
      correlate of penumbra.

PMID- 15459434
TI  - Recovery and rehabilitation in stroke: stem cells.
AB  - The recent demonstration that neurons for transplantation can be generated from
      stem cells and that the adult brain produces new neurons in response to stroke
      has raised hope for the development of a stem cell therapy for patients affected
      with this disorder. In this review we propose a road map to the clinic and
      describe the different scientific tasks that need to be accomplished to move stem
      cell-based approaches toward application in stroke patients.

PMID- 15459438
TI  - Amyloid angiopathy-related vascular cognitive impairment.
AB  - We review accumulating evidence that cerebrovascular amyloid deposition (cerebral
      amyloid angiopathy [CAA]) is an independent risk factor for cognitive
      dysfunction. The two population-based autopsy studies that have analyzed
      cognitive status during life as a function of CAA have each suggested deleterious
      effects of CAA on cognition even after controlling for age and Alzheimer disease
      pathology. We also review data from patients with CAA-related intracerebral
      hemorrhage (the one form of CAA that can be noninvasively recognized) suggesting
      associations of CAA with radiographic white matter abnormalities and cognitive
      impairment. These data highlight the importance of elucidating the effects of
      vascular amyloid on cerebrovascular function and of developing therapeutic
      strategies for this potentially widespread form of microvascular cognitive
      impairment.

PMID- 15459439
TI  - Estrogens, migraine, and stroke.
AB  - Epidemiological studies suggest the existence of close but complex relationships
      between estrogens, migraine, and stroke in women before menopause. Migraine,
      particularly without aura, is strongly influenced by estrogens as illustrated by
      the frequency of onset at puberty, of menstrual migraine, and of improvement
      during pregnancy. Migraine, particularly with aura, is a risk factor for ischemic
      stroke with a relative risk of 3, further increased by tobacco smoking and oral
      contraceptive use. The pathophysiological mechanism underlying these close
      relationships remains unknown. In practice, given the very low absolute risk of
      stroke in young women, there is no systematic contraindication to oral
      contraceptive use in young female migraineurs but rather a firm recommendation
      for no smoking and for the use of low-estrogen-content pills or progestogens
      only, particularly in migraine with aura.

PMID- 15459440
TI  - Current status of hemorrhagic stroke and acute nonthrombolytic ischemic stroke
      treatment.

PMID- 15459441
TI  - Delayed adaptation of the heart to stress: late preconditioning.
AB  - The early phase of preconditioning (PC) lasts 2 to 3 hours and protects against
      myocardial infarction, but not against stunning. In contrast, the late phase of
      PC lasts for 3 to 4 days and protects against both myocardial stunning and
      infarction, making this phenomenon more clinically relevant. Late PC is a genetic
      reprogramming of the heart that involves the activation of several stress
      responsive genes, which ultimately results in the development of a
      cardioprotective phenotype. Sublethal ischemic insults release chemical signals
      (nitric oxide [NO], adenosine, and reactive oxygen species) that trigger a series
      of signaling events (eg, activation of protein kinase C, Src protein tyrosine
      kinases, Janus kinases 1/2, and nuclear factor-kappaB) and culminates in
      increased synthesis of inducible NO synthase, cyclooxygenase-2, heme oxygenase-1,
      aldose reductase, Mn superoxide dismutase, and probably other cardioprotective
      proteins. In addition to ischemia, heat stress, exercise, and cytokines can also
      induce a similar series of events. Perhaps most importantly, many pharmacologic
      agents (eg, NO donors, adenosine receptor agonists, endotoxin derivatives, or
      opioid receptor agonists) can mimic the effects of ischemia in inducing the late
      phase of PC, suggesting that this phenomenon might be exploited therapeutically.
      The purpose of this review is to summarize the mechanisms that underlie the late
      phase of ischemic PC.

PMID- 15459442
TI  - Mechanisms of hemorrhagic transformation after tissue plasminogen activator
      reperfusion therapy for ischemic stroke.
AB  - Reperfusion therapy with tissue plasminogen activator (tPA) is a rational therapy
      for acute ischemic stroke. Properly titrated use of tPA improves clinical
      outcomes. However, there is also an associated risk of hemorrhagic transformation
      after tPA therapy. Emerging data now suggest that some of these potentially
      neurotoxic side effects of tPA may be due to its signaling actions in the
      neurovascular unit. Besides its intended role in clot lysis, tPA is also an
      extracellular protease and signaling molecule in brain. tPA mediates matrix
      remodeling during brain development and plasticity. By interacting with the NMDA
      type glutamate receptor, tPA may amplify potentially excitotoxic calcium
      currents. At selected concentrations, tPA may be vasoactive. Finally, by
      augmenting matrix metalloproteinase (MMP) dysregulation after stroke, tPA may
      degrade extracellular matrix integrity and increase risks of neurovascular cell
      death, blood-brain barrier leakage, edema, and hemorrhage. Understanding these
      pleiotropic actions of tPA may reveal new therapeutic opportunities for
      combination stroke therapy.

PMID- 15459443
TI  - Hormone replacement therapy and stroke: clinical trials review.
AB  - Bench research suggests that postmenopausal hormonal therapy is associated with
      beneficial effects on the brain and vascular system. Observational data suggest
      that postmenopausal hormone replacement therapy is associated with a 25% to 50%
      lower rate of cardiovascular disease; however, observational data for hormonal
      therapy is associated with the potential for significant biases. Clinical trial
      data are needed. There are 3 major clinical trials that inform us about stroke
      and postmenopausal hormone replacement therapy. Two trials focused on secondary
      prevention: the Heart and Estrogen/progesterone Replacement Study (HERS) and the
      Women's Estrogen for Stroke Trial (WEST). One examined primary prevention: the
      Women's Health Initiative (WHI). All indicate that postmenopausal hormone therapy
      is not effective for reducing the risk of a recurrent stroke or death among women
      with established vascular disease or for prevention of a first stroke. Similar
      results exist for cardiovascular disease. The results of these trials are now
      reflected in national guidelines. Hormone therapy should not be initiated to
      prevent vascular disease among postmenopausal women. As a result of these trials,
      the portion of postmenopausal women using hormone replacement therapy in the
      United States has fallen by more than half over the past decade.

PMID- 15459448
TI  - Structural analysis and identification of novel isoforms of the circadian clock
      gene period in the silk moth Bombyx mori.
AB  - The molecular basis of the circadian clock is an autoregulatory feedback loop in
      which the PAS domain-containing protein PERIOD periodically inhibits its own
      transcription. In the present study on PERIOD of the silk moth Bombyx mori, we
      have cloned two distinct period mRNA homologues with different PAS domain
      sequences either with or without the pentapeptide GTQEK. A period cDNA fragment
      first amplified by PCR exhibited a 15 bp-deleted nucleotide sequence in the PAS
      domain, compared with the database sequence. A possible alternative splicing
      mechanism was examined by PCR analyses, and a 15 bp-inserted clone was also
      amplified. The entire sequences of these period alpha and period beta isoforms
      were then determined by the 3' and 5' RACE methods. Isoform period alpha consists
      of a 3,324 bp oligonucleotide encoding 1,108 amino acid residues, whereas isoform
      period beta comprises 3,309 bp corresponding to 1,103 amino acids. Isoforms
      period alpha and period beta were found to be exactly identical except for the 15
      bp deletion/insertion site. Such a pair of isoforms with a deletion/insertion
      sequence, namely two splice variants, has previously been reported only for the
      PERIOD proteins of the two honeybees, Apis mellifera and A. cerana. The
      occurrence of an alternative splicing mechanism in the B. mori period gene was
      hypothesized based on the genome structure recently clarified. Bombyx mori PERIOD
      alpha and beta proteins are the isomers that reveal firstly the different PAS
      domain sequences.

PMID- 15459449
TI  - Developmental changes in dopamine modulation of the heart in the isopod
      crustacean Ligia exotica: reversal of chronotropic effect.
AB  - Developmental changes in dopamine modulation of the heart were examined in the
      isopod crustacean Ligia exotica. The Ligia cardiac pacemaker is transferred from
      the myocardium to the cardiac ganglion during juvenile development and the
      heartbeat changes from myogenic to neurogenic. In the myogenic heart of early
      juveniles, dopamine affected the myocardium and caused a decrease in the
      frequency and an increase in the duration of the myocardial action potential,
      resulting in negative chronotropic (decrease in beat frequency) and positive
      inotropic (increase in contractile force) effects on the heart. Contrastingly, in
      the heart of immature adults just after juvenile development, dopamine caused
      effects of adult type, positive chronotropic and positive inotropic effects on
      the heart affecting the cardiac ganglion and myocardium. During the middle and
      late juvenile stages, dopamine caused individually a negative or a positive
      chronotropic effect on the heart. These results suggest that the chronotropic
      effect of dopamine on the Ligia heart is reversed from negative to positive in
      association with the cardiac pacemaker transfer from the myocardium to the
      cardiac ganglion during juvenile development.

PMID- 15459450
TI  - Development and swimming behavior of Medaka fry in a spaceflight aboard the Space
      Shuttle Columbia (STS-107).
AB  - A space experiment aimed at closely observing the development and swimming
      activity of medaka fry under microgravity was carried out as a part of the
      S*T*A*R*S Program, a space shuttle mission, in STS-107 in January 2003. Four eggs
      laid on earth in an artificially controlled environment were put in a container
      with a functionally closed ecological system and launched on the Space Shuttle
      Columbia. Each egg was held in place by a strip of Velcro in the container to be
      individually monitored by close-up CCD cameras. In the control experiment, four
      eggs prepared using the same experimental set-up remained on the ground. There
      was no appreciable difference in the time course of development between space-
      and ground-based embryos. In the ground experiment, embryos were observed to
      rotate in place enclosed with the egg membrane, whereas those in the flight unit
      did not rotate. One of the four eggs hatched on the 8th day after being launched
      into space. All four eggs hatched in the ground unit. The fry hatched in space
      was mostly motionless, but with occasional control of its posture with respect to
      references in the experimental chamber. The fry hatched on ground were observed
      to move actively, controlling their posture with respect to the gravity vector.
      These findings suggest that the absence of gravity affects the initiation process
      of motility of embryos and hatched fry.

PMID- 15459451
TI  - Compensation of escape direction in unilaterally cercus-ablated crickets, Gryllus
      bimaculatus, is associated with the distance walked during recovery period.
AB  - In response to an air puff stimulus, intact crickets, Gryllus bimaculatus, make
      an escape almost 180 degrees opposite to the stimulus source. In order to verify
      our previous hypothesis that a self-stimulation of the wind-sensory system is
      necessary for a compensational recovery of the escape direction (behavioral
      compensation) in unilaterally cercus-ablated crickets, we investigated the
      relationship between the conditions of rearing after a unilateral cercal ablation
      and the degree of behavioral compensation. A unilaterally cercus-ablated cricket
      reared in a large cage to permit free locomotion showed a significantly higher
      degree of recovery of escape direction compared with those reared under
      restrained conditions in a small glass vial. However, the degree of behavioral
      compensation in a cricket reared alone in a large cage was smaller than that of
      crickets reared in a cage of the same size with 5-6 other cercus-ablated
      crickets. Mutual stimulation possibly increased the extent of locomotion of
      crickets reared in a group and improved the degree of compensational recovery of
      the escape direction. To ascertain this, the distance a cricket moved during the
      recovery period was associated with the degree of compensational change of the
      escape direction. The result suggests that the degree of compensation of the
      escape direction clearly depended on the distance walked by the crickets. The
      compensation seemed not to be caused by other factors such as chemical ones in
      the case of group rearing because forced locomotion induced by touch stimulation
      on the body surface was solely effective in improving the escape direction.

PMID- 15459452
TI  - Polymorphism of dopamine receptor D4 exon I corresponding region in chicken.
AB  - In stockbreeding, there are indications that behavioral traits of livestock have
      an effect on breeding and production. If the variation in individual behavior is
      related to that in neurotransmitter-related genes such as in humans, it would be
      possible to breed pedigrees composed of individuals having behavioral traits that
      are useful to production and breeding using selection based on genotypes. In this
      study, we investigated the exon I region of dopamine receptor D4 (DRD4), in which
      variation is related to psychiatric disorder in humans, in major poultry species
      namely Japanese quail (Coturnix japonica), chicken (Gallus gallus), ring-necked
      pheasant (Phasianus colchicus) and helmeted guinea fowl (Numida meleagris).
      Furthermore, we investigated Japanese cormorant (Phalacrocorax capillatus) and
      Japanese jungle crow (Corvus macrorhynchos) as an out-group. In these species of
      birds, the repeat of proline was identified in the region corresponding to the
      human polymorphic region. The repeat number was 9 in Japanese quail, ring-necked
      pheasant and Japanese cormorant; 12 in helmeted guinea fowl; and 3 in Japanese
      jungle crow. However, no polymorphism was found in these species. In contrast,
      polymorphism was observed in chicken and two alleles with 8 and 9 repeats were
      identified. Although 9 repeats (allele 9) were predominant in most chicken
      breeds, Black Minorca had only 8 repeats (allele 8). Intra-breed polymorphism was
      found in 6 out of 12 breeds, and two alleles (alleles 8 and 9) were detected in
      these breeds. This polymorphism, which is the first to be reported on a
      neurotransmitter-related gene in birds, would contribute significant information
      for elucidation of differences in behavioral traits in chicken breeds.

PMID- 15459453
TI  - Acoustic identification of eight species of bat (mammalia: chiroptera) inhabiting
      forests of southern hokkaido, Japan: potential for conservation monitoring.
AB  - Assessing the impact of forest management on bat communities requires a reliable
      method for measuring patterns of habitat use by individual species. A measure of
      activity can be obtained by monitoring echolocation calls, but identification of
      species is not always straightforward. We assess the feasibility of using
      analysis of time-expanded echolocation calls to identify free-flying bats in the
      Tomakomai Experimental Forest of Hokkaido University, Hokkaido, northern Japan.
      Echolocation calls of eight bat species were recorded in one or more of three
      conditions: from hand-released individuals, from bats flying in a confined space
      and from bats emerging from their roost. Sonograms of 171 calls from 8 bat
      species were analyzed. These calls could be categorized into 3 types according to
      their structure: FM/CF/FM type (Rhinolophus ferrumequinum), FM types (Murina
      leucogaster, Murina ussuriensis, Myotis macrodactylus and Myotis ikonnikovi) and
      FM/QCF types (Eptesicus nilssonii, Vespertilio superans and Nyctalus aviator).
      Sonograms of the calls of R. ferrumequinum could easily be distinguished from
      those of all other species by eye. For the remaining calls, seven parameters
      (measures of frequency, duration and inter-call interval) were examined using
      discriminant function analysis, and 92% of calls were correctly classified to
      species. For each species, at least 80% of calls were correctly classified. We
      conclude that analysis of echolocation calls is a viable method for
      distinguishing between species of bats in the Tomakomai Experimental Forest, and
      that this approach could be applied to examine species differences in patterns of
      habitat-use within the forest.

PMID- 15459454
TI  - A new species of the genus Hypsibius (Tardigrada: Parachela: Hypsibiidae) from
      Sakhalin island, far East Russia.
AB  - A new species of semiterrestrial eutardigrade, Hypsibius stiliferus, is described
      from Sakhalin Island, Far East Russia. The new species is distinguished from its
      congeners by having an irregular, polygonal or subtriangular dorsal sculpture,
      which increases in size posteriorly, two granular macroplacoids, and a cuticular
      bar near the base of posterior claw 4, and by lacking a microplacoid and
      septulum. It is currently known from its type locality and several other
      localities in northern and southern Sakhalin Island. This is the first report
      concerning tardigrades from Sakhalin Island.

PMID- 15459455
TI  - On the taxonomical status of Myotis abei YOSHIKURA, 1944 (Chiroptera,
      Vespertilionidae).
AB  - The type specimen of Myotis abei YOSHIKURA, 1944 was examined and compared with
      species of subgenera Leuconoe and Selysius from Japan and adjacent territories.
      The analysis of external characters and measurements indicated that M. abei
      should be recognised as a junior synonym of Myotis daubentoni (KUHL, 1817).

PMID- 15459456
TI  - Color-pattern modifications and speciation in butterflies of the genus Vanessa
      and its related genera Cynthia and Bassaris.
AB  - We have previously shown that the systemic injection of sodium tungstate, a
      protein-tyrosine phosphatase (PTPase) inhibitor, to pupae immediately after
      pupation efficiently produces characteristic color-pattern modifications on the
      wings of many species of butterflies including Vanessa indica and Cynthia cardui.
      In these species, the black spots reduced in size in response to the treatment.
      Similar modifications are occasionally seen in the field-caught aberrant
      individuals. Exceptionally, however, a C. cardui individual with enlarged black
      spots ("reversed" modification pattern) has been reported. Here we show that
      these modified patterns of V. indica and C. cardui are quite similar to the
      normal color-patterns of other Vanessa species. V. indica with tungstate-induced
      modifications resembled V. tameamea, V. samani, and Bassaris itea, whereas V.
      dilecta, V. atalanta, and V. dejeanii are similar to the "reversed" individual.
      Most features seen in the experimentally-modified V. indica were observed
      throughout the fore- and hindwings of V. samani. In contrast, the experimentally
      induced color-patterns of C. cardui did not parallel variation of Cynthia
      butterflies. Since it has been proposed that a hypothetical transduction pathway
      with a PTPase for the scale-cell differentiation globally coordinates the wing
      wide color-patterns, our findings suggest that spontaneous mutations in genes in
      this hypothetical pathway might have played a major role in creating new color
      patterns and species in the Vanessa genus but not in the Cynthia genus. This
      evolutionary mechanism may probably be shared more widely in Lepidoptera,
      although this would not be a sole determinant for the color-pattern development
      and evolution.

PMID- 15459457
TI  - Genetic structure of korean wild populations of the Medaka Oryzias latipes
      inferred from allozymic variation.
AB  - Previous allozymic studies have revealed that Korean wild populations of Oryzias
      latipes have differentiated regionally, and are composed of two distinct groups,
      the East Korean Population and the China-West Korean Population. Recently,
      mitochondrial DNA (mtDNA) sequencing and restriction fragment length polymorphism
      (RFLP) analyses have confirmed these two groups, and shown that the distribution
      ranges of the two groups overlap in western Korea. In order to describe the
      detailed distributions of the two groups and the gene flow between them,
      genotypes of 13 allozymic loci were determined in 444 specimens from 96
      localities in Korea. The two major groups were supported by remarkable allele
      frequency differences at six diagnostic loci: ACP*, AMY*, CK-A*, LDH-A*, PGM* and
      TF*. Individuals with the typical "eastern" genotype were mainly distributed in
      eastern and southern areas. In contrast, fish with the "western" genotype were
      predominant in the western area, and were further divided into two subgroups (the
      Han River and Geum River Subpopulations) by unique alleles at the ADH* locus. In
      the western coast, two distinct (eastern and western) genotypes were distributed
      in a mosaic fashion. This distribution pattern was identical to those from mtDNA
      analyses. Although the distribution patterns of the alleles at three loci (GPI
      A*, LDH-C* and SOD*) showed introgressive conditions between the two groups, each
      population was nearly fixed as either the eastern or western genotype at all six
      diagnostic loci despite the proximity among samples. Therefore, it is suggested
      that some reproductive isolation mechanisms exist between the two groups in
      natural habitats.

PMID- 15459458
TI  - Population differentiation in the Pacific white-sided dolphin Lagenorhynchus
      obliquidens inferred from mitochondrial DNA and microsatellite analyses.
AB  - We investigated genetic diversity and differentiation of the Pacific white-sided
      dolphin (Lagenorhynchus obliquidens) in Japanese coastal waters and offshore
      North Pacific by analyzing mitochondrial DNA and nuclear microsatellite
      variation. A total of 519 bp of the mitochondrial control region was sequenced
      and five microsatellite locus were genotyped for 59 individuals. A high level of
      haplotypic diversity (h=96.1%), moderate level of nucleotide diversity (pi=1.65%)
      and average expected heterozygosity (HE=0.66-0.76) were within an extent of those
      reported for other odontocetes. Consistent genetic difference between the samples
      from Japanese coastal Pacific-Sea of Japan and offshore North Pacific was
      indicated by analyses of molecular variance (AMOVAs) based on mtDNA and
      microsatellite variations, comparison of genetic variabilities, and geographical
      distributions of mtDNA haplotypes and microsatellite alleles. This result
      suggests that Pacific white-sided dolphins in each of the above two areas belong
      to different populations between which gene flow has been severely restricted.
      The low genetic diversity and mtDNA genealogy of the population in Japanese
      coastal waters suggest that it originated from a small population that colonized
      the Sea of Japan or that experienced population reduction when this Sea was
      isolated from the North Pacific during a glacial period in the Late Pleistocene.

PMID- 15459459
TI  - Volume-outcome relation for hospitals performing angioplasty for acute myocardial
      infarction: results from the Nationwide Japanese Registry.
AB  - BACKGROUND: The purpose of this study was to use a contemporary database to
      examine the relationship between annual hospital volume and the outcomes of
      percutaneous coronary interventions (PCIs) for acute myocardial infarction (AMI),
      given the wide spread use of coronary stents. An inverse relation exists between
      the number of PCIs and short-term outcome, but PCI practice has been changing
      with the availability of new devices such as stents. METHODS AND RESULTS: Data
      from the 1997 Japanese nationwide registry were analyzed to determine the
      relation between the annual hospital volume of PCI procedures for patients with
      AMI and in-hospital mortality, as well as the need for coronary artery bypass
      graft (CABG) surgery. A total of 129 hospitals (2,491 patients) were divided into
      terciles according to the annual volume. Of the procedures, 39% involved coronary
      stents. Median annual PCI volumes varied across terciles from low =10, middle
      =33, and high =89. After adjusting for patient characteristics, there was no
      significant relationship between volume and in-hospital mortality (trend P=0.66)
      and CABG (trend P=0.35). Among patients who received stents (n=958), there was no
      significant association between volume and either mortality or CABG. CONCLUSIONS:
      Using the contemporary database, there was no significant relationship between
      hospital volume and in-hospital outcome among AMI patients undergoing PCIs.

PMID- 15459460
TI  - Association of white blood cell count and clustered components of metabolic
      syndrome in Japanese men.
AB  - BACKGROUND: The role of inflammation in the genesis of cardiovascular disease has
      attracted attention and in the present study the association among metabolic
      syndrome (MS), white blood cell (WBC) count, and insulin concentration was
      investigated. METHODS AND RESULTS: A cross-sectional study of 3,594 Japanese men
      aged 34-69 years evaluated the MS components (high blood pressure, hypo-high
      density lipoprotein (HDL)-cholesterolemia, hypertriglyceridemia, hyperglycemia),
      as defined by the criteria given in the Third Report of the National Cholesterol
      Education Program Expert Panel on Detection Evaluation, and Treatment of High
      Blood Cholesterol in Adults, except for obesity [body mass index (BMI) >/=25
      kg/m(2)]. WBC count had a positive correlation with BMI, blood pressure,
      triglyceride, glucose and insulin, and a negative correlation with HDL
      cholesterol. The multi-adjusted means of WBC count and insulin concentration were
      significantly higher in MS subjects defined as having 3 or more of the components
      than in non-MS subjects with no more than 2 components. Both means also increased
      with the number of MS components (p<0.001 for trend). In the multiple linear
      regression analysis, BMI, HDL-cholesterol, systolic blood pressure, glucose and
      triglyceride had a significant and independent association with WBC count, but
      the insulin concentration did not. CONCLUSIONS: The cluster of MS components
      based on insulin resistance may cause low-grade inflammation.

PMID- 15459461
TI  - In normoglycemic Koreans, insulin resistance and adipocity are independently
      correlated with high blood pressure.
AB  - BACKGROUND: There is some controversy about the role of insulin resistance (IR)
      in the regulation of blood pressure (BP). Moreover, a large study of the
      association between BP and IR has not been conducted in normal glucose tolerance
      Asians. The present study investigated the relationships between IR, body mass
      index (BMI) and waist circumference and BP in normoglycemic Koreans. METHODS AND
      RESULTS: Anthropometric indices of adiposity, metabolic variables (fasting serum
      insulin and a homeostasis model assessment (HOMA) index of insulin sensitivity),
      BP and several cardiovascular risk factors were measured during a cross-sectional
      survey of 49,076 normoglycemic Korean subjects. A high BP was defined as a
      systolic BP >/=140 mmHg or a diastolic BP >/=90 mmHg. The prevalence of high BP
      by HOMA grading was 0.985 (95% confidence interval (CI) 0.857-1.132, p=0.835),
      1.180 (95% CI 1.032-1.350, p=0.016), 1.289 (95% CI 1.129-1.472, p<0.001), and
      1.540 (95% CI 1.341-1.768, p<0.001) times higher in subjects in the second,
      third, fourth, and fifth quintiles, respectively, compared with those in the
      first quintile. In addition, age, sex, waist circumference and BMI were found to
      be significantly associated with a high BP. CONCLUSION: IR, BMI and waist
      circumference are independently correlated with high BP in normoglycemic Koreans.

PMID- 15459462
TI  - Impact of the magnitude of the initial ST-segment elevation on left ventricular
      function in patients with anterior acute myocardial infarction.
AB  - BACKGROUND: In the percutaneous coronary intervention (PCI) era, the impact of
      initial ST-segment elevation magnitude on left ventricular (LV) function in
      patients with acute myocardial infarction (AMI) remains unclear. METHODS AND
      RESULTS: In the present study, 239 patients with total occlusion and 81 patients
      with spontaneous reperfusion within 12 h of their first anterior AMI were
      evaluated. The sum of ST-segment elevation (SigmaST) was measured in leads I,
      aV(L) and V(1-6) shortly before angiography. Predischarge LV ejection fraction
      (LVEF) was obtained at 15+/-5 days. In total occlusion, the predischarge LVEF was
      significantly lower in patients with SigmaST >/=10 mm than in those with SigmaST
      <10 mm (51+/-14% vs 57+/-14%, p<0.01). However, in spontaneous reperfusion, there
      was no significant difference between patients with ST >/=10 mm and those with
      SigmaST <10 mm (61+/-13 vs 62+/-14 %, p=NS). Predischarge LVEF significantly
      correlated with SigmaST in total occlusion (r=-0.25, p<0.01), but not in
      spontaneous reperfusion (r=0.03, p=NS). CONCLUSION: The results suggest that
      initial SigmaST is an important predictor of LV function in patients with total
      occlusion, but not in those with spontaneous reperfusion.

PMID- 15459463
TI  - Prevalence and electrocardiographic characteristics of idiopathic ventricular
      arrhythmia originating in the free wall of the right ventricular outflow tract.
AB  - BACKGROUND: The prevalence and ECG characteristics of idiopathic ventricular
      arrhythmia originating in the free wall of the right ventricular outflow tract
      (RVOT) require further clarification, which was the aim of the present study of
      110 patients with idiopathic ventricular tachycardia (n=34) or premature
      ventricular contraction (n=76; OT-VT/PVC) who underwent successful catheter
      ablation at the RVOT. METHODS AND RESULTS: Ten OT-VT/PVCs (9%) were ablated
      successfully at the free wall (FW-VT/PVC); the remaining 100 (91%) were ablated
      at the RVOT septum (Sep-VT/PVC). R wave amplitudes in the inferior leads were
      significantly smaller in FW-VT/PVC than in Sep-VT/PVC (p<0.01). An RR' pattern in
      the inferior leads was observed significantly more often in FW-VT/PVC than in Sep
      VT/PVC (p<0.001). QS-wave amplitude in each of leads V(1) to V(3) was
      significantly deeper in FW-VT/PVC than in Sep-VT/PVC (p<0.001). ECG criteria
      requiring an RR' pattern in all inferior leads as well as an S-wave amplitude of
      at least 3.0 mV in lead V(2) differentiated FW-VT/PVC from Sep-VT/PVC with high
      sensitivity, specificity, and predictive accuracy. CONCLUSIONS: Although FW
      VT/PVC has a relatively low prevalence, it has several distinctive ECG
      characteristics and detailed ECG analysis can differentiate it from Sep-VT/PVC.

PMID- 15459464
TI  - Diagnostic value of the recovery time-course of st slope on exercise ECG in
      discriminating false-from true-positive ST-segment depressions.
AB  - BACKGROUND: Using the exercise ECG for diagnosing coronary artery disease (CAD)
      is hampered by the occurrence of false-positive (FP) ST-segment depression.
      Because it is known that the recovery ST-T time-course in CAD differs from that
      in FP subjects, the ST slope may help discriminate FP from true-positive (TP)
      results. METHODS AND RESULTS: Treadmill digitized ECG from patients with
      significant ST-segment depressions and normal resting ECG were analyzed in 134
      patients with CAD on angiography (>50% narrowing) and reversible perfusion
      defects (TP group), and 64 subjects with normal perfusion (FP group) on exercise
      single photon emission computed tomography. The ST slope between the J-point and
      J(80) was measured every minute up to 6-min postexercise. The ST slope was
      significantly higher in FP than in TP at peak exercise, and at postexercise 1-, 2
      and 3-min (p<0.01, all). Thereafter, it gradually increased in TP, while
      monotonically decreasing in FP. Its decrease from 3- to 6-min could correctly
      diagnose 88% of FP subjects, whereas it was found in only 19% of TP patients
      (total accuracy 83%). CONCLUSIONS: The ST slope change from early to late
      recovery is a simple yet reliable marker for discriminating FP from TP ST-segment
      responses in subjects with a normal resting ECG.

PMID- 15459465
TI  - Correlation of plasma concentrations of B-type natriuretic peptide with infarct
      size quantified by tomographic thallium-201 myocardial scintigraphy in
      asymptomatic patients with previous myocardial infarction.
AB  - BACKGROUND: Secretion of A-type (atrial) and B-type (brain) natriuretic peptides
      (ANP and BNP) increases in relation to left ventricular (LV) dysfunction in
      patients with myocardial infarction (MI). However, it is unknown what determines
      the concentrations of ANP and BNP in asymptomatic MI patients with preserved LV
      function, so the aim of the present study was to examine if they are associated
      with MI size. METHODS AND RESULTS: Plasma concentrations of ANP and BNP in the
      peripheral blood were measured in 88 asymptomatic (New York Heart Association
      class I) patients with previous MI. The infarct size was quantitatively
      calculated from rest thallium-201 myocardial single photon emission computed
      tomography. In multivariate linear regression analysis that included MI size,
      hemodynamic parameters, and age as covariables, only BNP concentrations had a
      significant association with MI size (p=0.0001). In contrast, ANP concentrations
      were not significantly correlated with MI size in either the univariate or
      multivariate analysis. CONCLUSIONS: BNP but not ANP concentrations increased in
      proportion to the scintigraphic MI size despite the lack of heart failure in
      asymptomatic patients with previous MI. Thus, the increase in plasma BNP
      concentrations reflects the MI size, an important determinant of prognosis, in
      asymptomatic patients with MI.

PMID- 15459466
TI  - Effect of combined intracoronary adenosine and nicorandil on no-reflow phenomenon
      during percutaneous coronary intervention.
AB  - BACKGROUND: This study aimed to clarify the effect of intracoronary
      administration of combined adenosine and nicorandil on the no-reflow phenomenon.
      METHODS AND RESULTS: Fifty patients (67+/-10 years, 30 male) with acute
      myocardial infarction (AMI) who developed no-reflow phenomenon during primary
      percutaneous coronary intervention (PCI) between June 2001 and May 2003 comprised
      the study group, which was divided into 2 groups: group I [25 patients, 67+/-10
      years, 13 male; adenosine (24 microg/ml) alone in addition to nitrate] and group
      II [25 patients, 66+/-9 years, 17 male; combined intracoronary administration of
      adenosine and nicorandil (2 mg/ml) in addition to nitrate]. In-hospital and 6
      month major adverse cardiac events (MACE) after PCI were compared between the 2
      groups. Risk factors of coronary disease, left ventricular ejection fraction and
      wall motion score were not significantly different between the 2 groups (p=NS).
      Time interval from the onset of chest pain to PCI, number of involved vessels,
      lesion type according to ACC/AHA classification and TIMI flow grade (TFG) were
      not significantly different in both groups (p=NS). Incidence of thrombosis or
      dissection after balloon angioplasty, diameter and length of stent, and use of
      Reopro during PCI were not significantly different. TFG after PCI (2.0+/-0.9 vs
      2.6+/-0.6, p=0.024), DeltaTFG (1.5+/-1.1 vs 2.2+/-1.0, p=0.033) and difference in
      TIMI frame count (TFC) before and after PCI (DeltaTFC) were greater in group II
      than group I (45.2+/-24.5 vs 63.6+/-23.2, p=0.014). Myocardial blush score 3 was
      obtained more frequently in group II than group I (44% vs 76%, p=0.014). In
      hospital death did not occur in any of group II, but 4 patients of group I died
      (p=0.043). Two cases of MACE developed in each group and heart failure occurred
      in 3 (12%) of group I and 1 (4%) of group II patients during the 6-month follow
      up (p=NS). CONCLUSIONS: Intracoronary administration of adenosine combined with
      nicorandil may improve both the occurrence of no-reflow in patients during PCI
      for AMI and short-term clinical outcome, compared with adenosine alone.

PMID- 15459467
TI  - Right ventricular systolic function and the manner of transformation of the right
      ventricle in patients with dilated cardiomyopathy.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is generally considered to be
      accompanied by both left and right ventricular dysfunction, but most studies only
      analyze the left ventricular function. METHODS AND RESULTS: Biplane right
      ventriculography was performed in 13 control subjects and 13 patients with DCM
      and New York Heart Association functional class II. Three dimensions of the right
      ventricle (RV) (the long axis dimension (LA), the anterior - posterior dimension
      (AP), and the septum -free wall dimension (SF)) and 2 dimensions of the left
      ventricle (LV) (LA and AP) were examined to assess regional function. The group
      with DCM had a lower stroke volume index and RV ejection fraction. In the RV
      dimensional analysis, the group with DCM had a smaller SF and a larger AP at end
      diastole, and larger AP and LA at end-systole. There was a significant linear
      negative correlation between SF of RV and AP of LV at end-diastole. CONCLUSION:
      In clinically well-controlled cases of DCM, RV systolic function is depressed,
      and the RV is compressed by the LV, becoming less thick than in the controls.
      This transformation results from some parallel interaction between the RV and a
      markedly enlarged LV.

PMID- 15459468
TI  - Adaptation to low-intensity exercise on a cycle ergometer by patients with acute
      myocardial infarction undergoing phase I cardiac rehabilitation.
AB  - BACKGROUND: The adaptation of patients with acute myocardial infarction (AMI) to
      a phase I rehabilitation program has not been widely assessed. METHODS AND
      RESULTS: Forty-two male patients (62+/-8 years) with AMI were classified as
      exercise tolerant (group A, n=25) or excessive response (systolic blood pressure
      (SBP) increase >30 mmHg during exercise; group B, n=17). Hemodynamic parameters
      during exercise using a cycle-ergometer were monitored for the first 3 days. The
      power of low- and high-frequency components (LF: 0.05-0.2 Hz; HF: 0.2-1 Hz) was
      analyzed by heart rate variability. Anxiety status was assessed using the
      Spielberger's State-Trait Anxiety Inventory. Patients in group B were
      significantly older, had lower cardiac function and a longer hospitalization than
      group A (p<0.05, respectively). The excessive elevation of SBP on Day 1 decreased
      and became <30 mmHg on Day 3 in group B. The decreases in HF during exercise on
      Days 1 and 3 were significantly smaller in group B than in group A (p<0.05 and
      p<0.05, respectively). The LF/HF ratio on Day 1 was significantly higher in group
      B than in group A (p<0.05). In group B, the anxiety score before exercise was
      significantly higher than that at the time of discharge (p<0.05), whereas there
      was no change in group A. CONCLUSION: Factors influencing a significant elevation
      of blood pressure during phase I rehabilitation are age, physical deconditioning,
      imbalance of autonomic nervous activity and anxiety.

PMID- 15459469
TI  - Effect of physical training on corrected QT dispersion in patients with
      nonischemic heart failure.
AB  - BACKGROUND: The effect of physical training (PT) on QTc dispersion and
      ventricular tachycardia (VT) remains unclear in patients with nonischemic heart
      failure. METHODS AND RESULTS: Eight patients with nonischemic heart failure
      performed PT using a bicycle ergometer and their exercise tolerance increased
      (4.9+/-1.8 to 7.0+/-2.5 METs, p<0.05) and QTc dispersion decreased (71+/-22 to
      48+/-24 ms, p<0.05). However, PT did not change the frequency of VT. CONCLUSION:
      Physical training could improve QTc dispersion in patients with nonischemic heart
      failure, possibly by improving the autonomic nerve system.

PMID- 15459470
TI  - Detecting viable myocardium and predicting functional improvement: comparisons of
      positron emission tomography, rest-redistribution thallium-201 single-photon
      emission computed tomography (SPECT), exercise thallium-201 reinjection SPECT, I
      123 BMIPP SPECT and dobutamine stress echocardiography.
AB  - BACKGROUND: Low-dose dobutamine stress echocardiography (LDDE) has become a
      useful and safe method for identifying hibernating or stunned myocardium and for
      predicting improvement in wall motion after coronary revascularization. METHODS
      AND RESULTS: In the present study, fluorine-18 fluorodeoxyglucose positron
      emission tomography (FDG-PET), rest-redistribution thallium-201 ((201)Tl) single
      photon emission computed tomography (RR-Tl SPECT), (123)I-15-(p-iodophenyl)-3
      (R,S)-methyl pentadecanoic acid (BMIPP) and LDDE were performed in 30 patients
      with acute myocardial infarction (AMI) at 10+/-3 days after the onset of AMI.
      Also, exercise (201)Tl reinjection SPECT (RI-Tl SPECT) was performed at 14+/-2
      days. Follow-up echocardiography was performed 5+/-3 months later in all patients
      after interventional therapy for the assessment of functional recovery. Of the
      390 segments analyzed by echocardiography, 110 (28%) had abnormal wall motion.
      There were no significant differences between RR-Tl SPECT and LDDE in
      sensitivity, specificity, positive predictive value and negative predictive value
      using the chi(2)-test; however, in akinetic segments, there was a significant
      difference in sensitivity. Among FDG-PET, RI-Tl SPECT, BMIPP and LDDE, there were
      significant differences in 3 variables. In akinetic segments, LDDE is superior to
      RR-Tl SPECT in sensitivity and to FDG-PET in specificity. In hypokinetic
      segments, LDDE is superior to RI-Tl SPECT and BMIPP in sensitivity, and to FDG
      PET and BMIPP in specificity. CONCLUSIONS: LDDE could detect functional recovery
      of viable myocardium in the early period of AMI and can be performed easily and
      safely.

PMID- 15459471
TI  - Transient improvement of left ventricular function after peripheral blood stem
      cell transplantation in a patient with myelodysplastic syndrome and dilated
      cardiomyopathy.
AB  - A patient who had myelodysplastic syndrome (MDS) and dilated cardiomyopathy (DCM)
      had a transient improvement of cardiac function after peripheral blood stem cell
      transplantation (PBSCT). When he was admitted to hospital for PBSCT, a chest X
      ray showed cardiomegaly, and Tc-99m quantitative gated single photon emission
      computed tomography (QGS) showed increases in left ventricular (LV) volumes and a
      decrease in LV ejection fraction (LVEF). A coronary angiogram showed no evidence
      of coronary artery disease. Left ventriculography showed similar findings as QGS,
      and the findings from a myocardial biopsy were compatible with DCM. Three months
      after a successful allo-PBSCT with his brother as the donor, the cardiomegaly had
      been attenuated, the LV volumes decreased and LVEF increased on the QGS images.
      However, 10 months later, his cardiac function had deteriorated. The changes in
      cardiac function did not correlate with the hematological changes, such as the
      hemoglobin level.

PMID- 15459472
TI  - Primary cardiac tumor presenting as obstruction of the left ventricular outflow
      tract.
AB  - A transthoracic echocardiogram revealed 3 tumors in the left atrium of a 64-year
      old woman, who died suddenly 8 months after resection of the tumors. Primary
      cardiac tumors are unusual and a case of postoperative left ventricular
      metastases of the atrial tumors resulting in left ventricular outflow tract
      obstruction is very rare occurrence.

PMID- 15459473
TI  - Isolated noncompaction of the left ventricular myocardium in an elderly patient.
AB  - Noncompaction of the ventricular myocardium (NVM) is a rare disorder of
      endomyocardial morphogenesis characterized by numerous, prominent trabeculations
      and deep intertrabecular recesses. It is commonly associated with congenital
      heart disease, but the isolated form (INVM) is not associated with other
      structural heart diseases. Clinical reports of INVM have been limited to a few
      case reports and small series of pediatric patients. INVM is considered to be a
      form of congenital abnormal endomyocardial morphogenesis caused by abnormal
      cessation of the embryonic development of the ventricular myocardium; most
      reported cases have been pediatric patients, and autopsy cases of elderly
      patients have been quite rare. In the present case, an elderly female had INVM
      associated with severely disturbed left ventricular (LV) function and an enlarged
      left ventricle similar to dilated cardiomyopathy. The echocardiogram showed
      prominent trabeculations and deep intertrabecular recesses of the LV walls,
      especially in the posterior and apical areas. LV contrast echocardiography
      revealed markedly protruberant trabeculations, which were also observed with
      computed tomography. Five years later, the patient died of refractory heart
      failure and ventricular fibrillation. The autopsy revealed numerous excessively
      prominent trabeculations in the LV myocardium, with deep intertrabecular recesses
      containing thrombi.

PMID- 15459474
TI  - Beneficial effect of cibenzoline on left ventricular pressure gradient with
      sigmoid septum.
AB  - An 83-year-old woman with hypertension was admitted to hospital with episodes of
      dyspnea on effort after having breakfast. Physical examination revealed a
      systolic murmur at the left sternal border in the third to fourth intercostal
      space. Cross-sectional echocardiography showed a sigmoid-shaped interventricular
      septum markedly protruding into the left ventricle, concentric left ventricular
      hypertrophy, systolic anterior motion of the mitral valve, and a resultant left
      ventricular outflow tract obstruction with a pressure gradient of 121.8 mmHg. She
      began daily treatment with 60 mg metoprolol. However, the chest symptoms were not
      relieved and the left ventricular outflow tract obstruction was still visible on
      echocardiography. She was then given 200 mg daily of cibenzoline, in addition to
      40 mg metoprolol, and the left ventricular pressure gradient significantly
      decreased and she was free of symptoms without any complications. This case shows
      that cibenzoline may be useful in the treatment of left ventricular outflow tract
      obstruction caused by sigmoid septum.

PMID- 15459475
TI  - Gadopentetate dimeglumine as a potential alternative contrast medium during
      percutaneous coronary intervention: a case report.
AB  - BACKGROUND: There have not been previous reports of patients undergoing
      percutaneous coronary intervention (PCI) using a gadolinium chelate. METHODS AND
      RESULTS: A 74-year-old woman, who had a history of anaphylactic shock 4 times in
      response to iodinated contrast media despite preprocedural intravenous
      administration of hydrocortisone, was hospitalized because of unstable angina
      refractory to intensive medical treatment. Fully considering the risks of
      iodinated agents, digital subtraction coronary angiography and PCI were performed
      using gadopentetate dimeglumine without any side effects or complications.
      CONCLUSIONS: Gadolinium chelates can be an alternative contrast media during PCI
      in particular patients with contraindications to iodinated media.

PMID- 15459476
TI  - Method for selecting populations of rat articular chondrocytes that exhibit
      distinct growth and metabolic characteristics, and their responses to growth
      factors, PMA and vitamin D3.
AB  - Chondrocytes were released from articular cartilage fragments of 6-week-old
      Wistar rats by a 2-hour treatment with bacterial collagenase. The cells from one
      animal were seeded in a 25-cm2 culture flask at a density of 10(5) cells/cm2.
      After 1 h, the flask was gently shaken and the medium, containing nonadherent
      cells, was transferred to a new flask. The attached cells were incubated with 5
      ml of fresh medium. This procedure was repeated after 3, 24, 48 and 96 h.
      Resulting cell populations were then analyzed. The earlier cells attached, the
      more rapidly they proliferated, and the less collagen and proteoglycan (PG) they
      produced. The cells that attached after 24 h grew much more slowly, piled up in
      many areas, exhibited strong alkaline phosphatase activity and calcified
      extracellular matrix (ECM). Differences in deoxyribonucleic acid (DNA) and
      protein/PG synthesis were also observed when these cell populations were
      challenged with growth factors and 12-myristate 13-acetate (PMA). Pretreatment of
      cells for 2 h with PMA strongly enhanced DNA and PG synthesis only in cultures
      containing insulin-like growth factor-1. Nonselected rat articular chondrocytes
      (AC) subcultured at least four times as monolayers still expressed mRNA specific
      for aggrecan and type II collagen, suggesting conservation of the chondrogenic
      phenotype. In conclusion, AC of young individuals seem to be heterogeneous with
      respect to their capacity to proliferate and synthesize ECM. By selecting and
      expanding in vitro the appropriate cell population, this method could be
      potentially useful for studies aimed at repairing damaged cartilage.

PMID- 15459477
TI  - In vivo overexpression of tuftelin in the enamel organic matrix.
AB  - The primary sequences of human and mouse tuftelin are 89% identical. Both
      proteins comprise 390 amino acids and produce an acidic protein with an
      isoelectric point of 5.7, and an unmodified molecular weight of 44 kD. Using
      fluorescent-tagged tuftelin and amelogenin plasmid constructs we saw little
      evidence that these two enamel proteins colocalize in ameloblast-like LS-8 cells.
      Tuftelin is primarily localized to distinct 'speckled' domains within the cell
      cytoplasm. In an attempt to better define a physiological function for tuftelin
      during amelogenesis, we have produced transgenic mice that overexpress tuftelin
      in ameloblasts and subsequently the enamel matrix. Tuftelin overexpression
      impacts dramatically upon the enamel crystallite habit and the enamel prismatic
      structure. Overexpressing tuftelin results in gross imperfections in enamel that
      is evident both at the nanoscale and the mesoscale. The most notable difference
      observed in the transgenic animals, when compared to wild-type animals, is an
      apparent loss of restricted growth of enamel crystallites along their a-axis and
      b-axis. This equates to a change in the crystallite aspect ratio. In the
      transgenic animals the crystallite structures appear more 'plate'-like in
      contrast to the symmetric, 'ribbon'-like crystallite morphology that is a
      characteristic feature of mammalian enamel.

PMID- 15459478
TI  - Expression of wee1 and its related cell cycle components in mouse early stage
      follicles.
AB  - Wee1 is a kinase regulator of the M-phase promoting factor (a complex of cdc2 and
      cyclin B1). The present study was performed to determine the role(s) of wee1 in
      the early stages of mouse ovarian follicles. Expression of wee1 and the
      correlated cell cycle components, namely cdc2, cyclin B1, and cdc25C, was
      evaluated by immunohistochemistry. In addition, expression of Tyr15
      phosphorylated cdc2 (cdc2-p) was also examined to determine whether wee1 kinase
      phosphorylates cdc2. Each component except cdc25C was found in the oocyte
      cytoplasm at all follicular stages, while cdc25C was not detected in primordial
      follicles. It was found primarily in ovarian interstitial cells and to a small
      extent in granulosa cells of the developing secondary follicles. To further
      confirm the expression of cell cycle components in the primordial follicular
      oocytes, day 1 ovaries were enzymatically and mechanically dissociated, then
      oocytes were isolated from somatic cells including pre-granulosa cells, and we
      confirmed that cdc2-p was expressed in oocytes of primordial follicles. The
      results of the present study led to the conclusion that wee1, without the
      counteracting cdc25C, would cause meiotic arrest of oocytes by inhibitory
      phosphorylation of cdc2. Expression of all these proteins in the granulosa cells
      of growing follicles may regulate granulosa cell mitosis concurrently with the
      growth of oocytes and follicles.

PMID- 15459479
TI  - Expression patterns of PSA-NCAM in the human ganglionic eminence and its
      vicinity: role of PSA-NCAM in neuronal migration and axonal growth?
AB  - The ganglionic eminence (GE) is a transient but conspicuous structure of the
      developing forebrain which not only gives rise to a large number of precursor
      neurons and glial cells for various structures of the forebrain, but in addition
      serves as an intermediate target for growing axons to the cerebral cortex. To
      investigate the roles of the highly polysialylated isoform of the neural cell
      adhesion molecule (PSA-NCAM) in cell migration and axonal growth within the GE
      and its neighbouring structures, the spatio-temporal expression pattern of PSA
      NCAM was examined in human fetal forebrains between 14 and 36 weeks of gestation
      with a specific immunohistochemical method. Scattered PSA-NCAM-positive cells
      were found in the centre but more frequently in the marginal zone of the GE.
      Intensely labelled cells were also identified in the gangliothalamic body,
      basolateral nuclei of the amygdala and the subventricular and intermediate zone
      adjacent to the GE. This cellular immunoreactivity started to appear in various
      structures during the period from 14 to 19 weeks and gradually diminished after
      25-28 weeks. Strong immunoreactivity was also detected in fibres running from the
      intermediate zone of the neocortex to the internal capsule from 16 weeks onwards,
      and after 24 weeks, the immunoreactivity was gradually decreased. In the vicinity
      of the GE, between 16 and 22 weeks, short fibre bundles were observed to leave
      the longitudinally oriented axons of the internal capsule to reach the marginal
      zone of the GE. Our results suggest a close relationship between PSA-NCAM
      expression and neuronal migration (over short distances) and transitory axonal
      projections (target recognition and axonal fasciculation) in the region of the
      GE.

PMID- 15459480
TI  - The internal structure of the nucleus geniculatus lateralis ventralis in the
      avian brain: a Golgi study and electron microscopic investigation.
AB  - Different types of neurons in the ventral geniculate nucleus of the thalamus of
      chicks were visualised by Golgi impregnation. The dendritic tree of projection
      neurons branched in a sphere-like territory in both the ventral and middle areas
      of the lamina externa. The dendrites of projection neurons in the lamina interna
      descended into the lamina externa and entered both the ventral and middle
      dendritic areas. One or two dendrites of the lamina interna neurons also emitted
      branches that developed a dorsal sphere-like dendritic territory. Optic terminals
      labelled by Golgi impregnation or injection of biotinylated dextran amine were
      found in these dendritic territories gathered into groups. They established
      synapses in these areas (synaptic islands or fields without a glial sheath) with
      different dendritic profiles, and a few gamma-aminobutyric acid (GABA)-positive
      terminals synapsed with them. No glomerulus-like synaptic complexes ensheathed by
      glial processes were found. Optic terminals also contacted the stem dendrites of
      projection neurons and GABA-positive neuron cell bodies and dendrites. Numerous
      synapses established by both optic and GABA-positive terminals were found on the
      proximal dendritic stems of the lamina interna projection neurons.

PMID- 15459481
TI  - Cytochemical analysis of pancreatic islet hypercytolipidemia following diabetes
      (db/db) and obese (ob/ob) mutation expression: influence of genomic background.
AB  - Both diabetes (db/db) and obese (ob/ob) genotype mutations induce a hyperglycemic
      hyperinsulinemic endometabolic state in C57BL mice, manifesting a type II NIDDM
      diabetes-obesity syndrome (DOS) in these leptin ligand/receptor-deficient models.
      The severity of the DOS induced by these single gene, homozygous-recessive
      mutations may be moderated by the background genome on which the mutation is
      expressed. The current studies define the phenotypic, systemic, cytochemical and
      cellular metabolic responses to db/db and ob/ob mutation expression when modified
      by /KsJ (severe DOS expression) or /6 (modified DOS expression) background strain
      influences as compared to littermate control (+/?) indices. Both db/db and ob/ob
      mutations induced dramatic increases in body weights, blood glucose and serum
      insulin concentrations relative to +/? indices when expressed on either the
      C57BL/KsJ (-/KsJ) or C57BL/6 (-/6) backgrounds. However, the -/KsJ background
      enhanced the severity of expression of these DOS indices relative to the -/6
      strain. Similarly, the -/KsJ genome suppressed cellular glucose uptake rates,
      pancreatic tissue weights and insulin concentrations in both db/db and ob/ob
      mutants relative to /6 background strain influences or +/? indices. Concurrent
      enhancement of tissue and cellular lipogenic metabolism and islet cytolipid
      depositions were exaggerated when the mutations were expressed on the -/KsJ
      background relative to the -/6 genome. Pancreatic islet B-cell lipodeposition was
      markedly enhanced in ob/ob and db/db mutants expressed on either the -/KsJ or -/6
      background. In both ob/ob and db/db models, B-cell insulin granulation was
      prominent in mildly hypertrophic pancreatic islets when the mutations were
      expressed on the -/6 background. In contrast, the severity of the DOS state
      expressed on the -/KsJ background resulted in pronounced B-cell atrophy,
      characterized by insulin degranulation, cellular hypertrophy and
      hypercytolipidemia associated with tissue involution, in both ob/ob and db/db
      mutants. Dramatic alterations in tissue norephinephrine (NE) and alpha-1-receptor
      populations in ob/ob and db/db mutants were exaggerated by the -/KsJ genome as
      compared to -/6 or control indices. The influences of the -/KsJ genome on the
      progressive expression of tissue NE counter-regulatory responses to enhanced
      cytolipidemic indices were inversely related, with cytochemical lipodeposition
      occurring under conditions of diminished adrenergic responses to the DOS indices.
      The results of these studies indicate that the severity of the type-II diabetes
      endometabolic syndrome induced by the ob/ob or db/db genotypic mutations is
      modified by the existing genome on which the mutations are expressed. These data
      suggest that the severity of genomic mutation expression may be modified
      depending on the capability of the background genome to counter-regulate the
      systemic, cellular or metabolic consequences of these mutations.

PMID- 15459482
TI  - Cell proliferation profile of five human uveal melanoma cell lines of different
      metastatic potential.
AB  - OBJECTIVE: The aim of this study was to establish a proliferation profile of
      uveal melanoma cell lines, using different methods, and to compare it with their
      previously determined metastatic potential (MP). METHODS: Four human uveal
      melanoma and one transformed human uveal melanocytic cell line were ranked
      according to proliferation profiles. The proliferation profiles of the cell lines
      were compared to their MPs, which were previously determined from an
      immunosuppressed rabbit model. RESULTS: Ranking of the cell lines using pulse
      labeling with tritiated thymidine was similar to the MP of the cell lines.
      CONCLUSION: The correlation between the proliferative rate of the uveal melanoma
      cell lines and their previously determined MP resulted in the proposal of a new
      classification scheme: high proliferation/high MP, low proliferation/low MP, and
      high proliferation/no MP. High proliferative capacity of a cell line did not
      necessarily confer MP; therefore, further cellular functions/adaptations must be
      required for tumor cell dissemination, survival, and growth at a metastatic site.

PMID- 15459483
TI  - Involvement of CD14 in lipopolysaccharide- induced liver injury in mice
      pretreated with Propionibacterium acnes.
AB  - OBJECTIVE: The aim of this study was to elucidate the role of CD14 in the
      Propionibacterium acnes-lipopolysaccharide (LPS) system. METHODS AND RESULTS:
      CD14 transgenic mice (M14M), which expressed heterotopic CD14 and showed
      decreased responses to LPS in vivo, were used. Seven days after priming, the size
      of granulomas induced by an intraperitoneal administration of P. acnes in the
      M14M mice was smaller than that in the nontransgenic mice. The number of CD14
      positive cells in granulomas was also decreased in the M14M mice compared to the
      nontransgenic mice. An LPS challenge induced apoptotic and necrotic changes in
      hepatocytes in the nontransgenic mice but not in the M14M mice. Seven days after
      priming, tumor necrosis factor-alpha expression was found in monocytic cells in
      granulomas and Kupffer cells in the nontransgenic mice and was significantly
      upregulated after LPS injection, whereas the expression was very weak in these
      cells in the M14M mice. CONCLUSIONS: CD14 plays a role in the P. acnes-LPS system
      in both priming and induction phases.

PMID- 15459484
TI  - Expression of angiogenic factors is upregulated in DMBA-induced rat mammary
      pathologies.
AB  - OBJECTIVE: In the 7,12-dimethylbenz[a]anthracene (DMBA) model of rat mammary
      carcinogenesis, microvascular density and angiogenic potential increase with
      progression from normal to invasive disease, but the mechanisms involved are
      unknown. Using RT-PCR, we determined the expression of angiogenic regulators in
      DMBA-induced intraductal hyperplasia (IDP), carcinoma in situ (CIS), invasive
      tumors (INV), as well as normal tissue. METHODS: RT-PCR was performed on frozen
      tissue sections of each type of pathology for factors known to regulate
      angiogenesis in other systems. RESULTS: MMP-2, MMP-9, uPA, PAI-1, IGF-2, BFGF,
      VEGF, ANG-1, IRS-1, and TSP-1 were significantly (p < or =0.05) upregulated in
      CIS and INV, whereas TIMP-1, ANG-2, MASPIN, IGF1-R and HBEGF were unchanged. IGF
      1 was uniquely elevated in IDP. SPARC was downregulated in CIS. Inhibition of IGF
      1R by the tyrphostin, AG1024, blocked endothelial tubulogenesis in vitro,
      confirming that IGF-1 functions as a regulator of angiogenesis. CONCLUSIONS:
      These data support the involvement of specific angiogenic mediators in mammary
      tumor formation. Angiogenesis at different stages of tumorigenesis may be
      regulated by unique factors.

PMID- 15459485
TI  - Overexpression of 15-lipoxygenase in the vascular endothelium is associated with
      increased thymic apoptosis in LDL receptor-deficient mice.
AB  - BACKGROUND: 15-Lipoxygenase (15-LO) is a nonheme iron-containing enzyme that
      catalyzes the peroxidation of fatty acids. Herein, we studied the effect of 15-LO
      overexpression in the vascular endothelium on thymocyte apoptosis by evaluating
      thymuses from low-density lipoprotein receptor-deficient (LDL-RD) mice and LDL
      RD/15-LO mice. Thymuses were evaluated by immunohistochemistry and by TUNEL
      whereas in vitro studies were carried out by employing freshly isolated
      thymocytes from the respective mice and evaluation of apoptosis by propidium
      iodide and annexin V cytometry. METHODS AND RESULTS: The apoptotic index in LDL
      RD/15-LO mice was significantly higher than in the LDL-RD mice. In the thymic
      medulla the difference was smaller, although still significant. Freshly isolated
      thymus cells from LDL-RD/15-LO mice exhibited a higher rate of spontaneous cell
      death than controls. Incubation of thymus cells in the presence of the cell
      permeable caspase-3 inhibitor DEVD-CMK resulted in a decrease in the frequency of
      apoptotic cells in LDL-RD/15-LO thymocytes, whereas no effect was evident in
      control thymocytes. The antioxidant N-acetylcysteine causes the increase in
      apoptosis in both groups. CONCLUSION: LDL-RD/15-LO mice exhibit increased
      thymocyte apoptosis both in vivo and in vitro. These findings may suggest a role
      for 15-LO in the natural selection of thymocytes.

PMID- 15459486
TI  - Expression of heart-type fatty acid-binding protein in human gastric carcinoma
      and its association with tumor aggressiveness, metastasis and poor prognosis.
AB  - OBJECTIVE: Fatty acid-binding proteins (FABPs) are involved in lipid metabolism
      by intracellular transport of long-chain fatty acids. Heart-type (H-) FABP has
      been reported to inhibit cell growth and induce cell differentiation, but to our
      knowledge the significance of H-FABP expression in human gastric carcinoma has
      not been elucidated. The aim of the current study was to examine the expression
      of H-FABP and its relation to clinicopathologic parameters and fatty acid
      synthase (FAS) status of gastric carcinoma, since gastric cancer shows increased
      expression of FAS. METHODS: Immunohistochemistry with anti-H-FABP antibody was
      performed in 669 gastric carcinomas and 60 tubular adenomas of the stomach. H
      FABP-positive and H-FABP-negative carcinomas were analyzed for their
      clinicopathologic characteristics and FAS status. RESULTS: None of the adenomas
      expressed H-FABP, whereas 127 of 669 carcinomas (19.0%) were positive for the
      protein. H-FABP positivity was associated with the depth of invasion (p <0.0001),
      vascular invasion (p <0.0001), lymph node metastasis (p <0.0001), hepatic
      metastasis (p=0.0011), stage of the carcinoma (p <0.0001) and FAS status of the
      carcinoma (p=0.0476). A higher survival rate was noted in H-FABP-negative cases
      compared with H-FABP-positive cases (p=0.0004). CONCLUSIONS: A subset of human
      gastric carcinoma expresses H-FABP and its expression is associated with FAS
      status, disease progression, tumor aggressiveness and poor patient survival.

PMID- 15459487
TI  - Investigation of the prognostic value of TNF-alpha gene polymorphism among
      patients treated with infliximab, and the effects of infliximab therapy on TNF
      alpha production and apoptosis.
AB  - OBJECTIVES: Infliximab, a chimeric anti-tumor necrosis factor (TNF) antibody, is
      highly effective for the treatment of Crohn's disease (CD) and rheumatoid
      arthritis (RA). Our experiments focused on RA and CD patients receiving
      infliximab. Since cytokine production is largely determined by genetic factors,
      the promoter polymorphisms of TNF-alpha were examined among these patients.
      Additionally, the changes caused by infliximab in the TNF-alpha-producing ability
      and apoptosis of peripheral blood mononuclear cells (PBMCs) were investigated.
      METHODS: The TNF-alpha genotypes were analyzed by PCR-RFLP. The in vitro TNF
      alpha production of the PBMCs was detected by flow cytometric analysis. The TNF
      alpha concentration in the supernatant was measured by bioassay. Apoptosis was
      detected by annexin V-fluorescein isothiocyanate labeling. RESULTS AND
      CONCLUSIONS: 8 of the 12 nonresponder patients carried the TNF A allele
      associated with high TNF-alpha production. We suggest that the determination of
      TNF polymorphism may help identify more suitable candidates for infliximab
      treatment. Although in vitro infliximab treatment for 48 h resulted in
      significant (44.2 +/- 1.17%) apoptosis in PBMCs, in ex vivo samples from RA
      patients who received infliximab, apoptosis was only 13.3 +/- 1.6%. Furthermore,
      infliximab did not result in irreversible inhibition of the TNF-alpha-producing
      ability or in the significant apoptosis of PBMCs.

PMID- 15459488
TI  - Expression of c-myc mRNA in hepatocellular carcinomas, noncancerous livers, and
      normal livers.
AB  - OBJECTIVES: c-myc is a transcription factor that regulates cell proliferation,
      differentiation, and apoptosis. However, little is known about the clinical
      importance of c-myc mRNA expression in a primary hepatocellular carcinoma (HCC).
      In this study, we investigated whether a correlation existed between the level of
      c-myc mRNA expression and the occurrence of apoptosis or proliferative activity
      in an HCC. METHODS: The levels of c-myc mRNA expression were quantified by real
      time reverse transcriptase polymerase chain reaction (RT-PCR) and compared with
      immunohistochemical detection of the occurrence of spontaneous apoptosis and
      proliferative activity of cancer cells in 59 surgically resected HCCs. RESULTS:
      The mean level of c-myc mRNA expression in 59 HCCs (1.19) was significantly
      suppressed compared with that in 59 noncancerous liver tissues (1.44, p<0.0001).
      The level of c-myc mRNA expression was not correlated with tumor differentiation,
      tumor progression, proliferative activity of cancer cells, or patient survival.
      However, there was a significant positive correlation between the levels of c-myc
      mRNA expression and the occurrence of apoptosis in 59 HCCs (p<0.001).
      CONCLUSIONS: Inhibition of c-myc mRNA expression may obstruct the induction of
      apoptosis of HCC cells and lead to uncontrolled cell growth.

PMID- 15459489
TI  - Protein kinase C alpha expression in breast and ovarian cancer.
AB  - In recent years research has focused on the development of specific, targeted
      drugs to treat cancer. One approach has been to block intracellular signaling
      proteins, such as protein kinase C alpha (PKC-alpha). To help support the
      rationale for clinical studies of a PKC-alpha-targeted therapy in breast and
      ovarian cancers, we reviewed publications studying PKC-alpha expression in these
      tumors. Since these investigations were mostly performed in cell lines, we
      supplemented this review with some preliminary findings from studies examining
      PKC-alpha expression in tumor tissue biopsies obtained from patients with breast
      and ovarian cancer. Based on the reviewed publications using representative cell
      lines and our preliminary findings on tumor tissue of patients with breast
      cancer, we infer that PKC-alpha levels may especially be increased in breast
      cancer patients with low or negative estrogen receptor (ER) levels. Thus,
      clinical studies determining efficacy of selective or specific inhibitors of PKC
      alpha should include determination of ER status in order to help answer whether
      blocking PKC-alpha in patients with low or absent ER can result in clinical
      benefit.

PMID- 15459490
TI  - Prognostic value of syndecan-1 expression in breast cancer.
AB  - OBJECTIVE: Syndecan-1 is a cell surface heparan sulphate proteoglycan which
      participates in cell proliferation, cell migration and cell-matrix interactions.
      Epithelial syndecan-1 expression is reduced in several malignant tumours, but in
      breast and pancreatic cancer, increased expression has also been described. Loss
      of epithelial syndecan-1 has been associated with poor prognosis in some forms of
      cancer, but previous findings in breast cancer have been contradictory. The
      objective of this study was to evaluate the prognostic value of the
      immunohistochemical expression of syndecan-1 in a series of 200 patients with
      invasive breast cancer with a median follow-up of 17 years. METHODS: Formalin
      fixed paraffin-embedded specimens were stained using a monoclonal antibody
      against syndecan-1. RESULTS: Syndecan-1 was expressed in the epithelium in 61%
      and in the stroma in 67% of the tumours. Epithelial syndecan-1 expression was
      associated with negative oestrogen receptor (ER) status (p < 0.01), and stromal
      syndecan-1 expression with positive ER status (p = 0.02). The breast cancer
      specific 10-year overall survival for patients with epithelial syndecan-1
      expression was 65%, compared with 82% for those with loss of epithelial
      expression (p = 0.02). Ten-year survival was 66% for those expressing stromal
      syndecan-1 and 83% for those lacking stromal expression (p = 0.15). Patients with
      both epithelial and stromal expression had a 10-year survival of only 56%,
      compared to 78% in patients with other expression pattern combinations (p <
      0.002). In Cox multivariate analysis, only axillary involvement and tumour size
      were significant predictors of breast cancer-specific survival. CONCLUSION:
      Concomitant expression of syndecan-1 in both epithelium and stroma may be a
      predictor of unfavourable prognosis in breast cancer, and in contrast with
      previous studies, loss of epithelial syndecan-1 was associated with a more
      favourable prognosis.

PMID- 15459491
TI  - Prognostic significance of tumor markers in peritoneal lavage in advanced gastric
      cancer.
AB  - OBJECTIVE: Predicting peritoneal dissemination of cancer is very difficult
      whatever method of examination is used. Recently, a cytological examination of
      peritoneal lavage has been shown to be a feasible measure to predict an early
      state of peritoneal seeding. The predictive value of the levels of tumor markers
      in peritoneal lavage for peritoneal metastasis from gastric carcinoma was thus
      studied. METHODS: In 229 patients gastric cancer tumor markers, CEA, CA 125, and
      CA 19-9, in peritoneal lavage were intraoperatively evaluated using a
      chemiluminescent enzyme immunoassay. RESULTS: CEA in peritoneal lavage at a
      cutoff level of 0.5 ng/ml showed overall a higher sensitivity of 75.8% at a
      specificity of 90.8% for a diagnosis of peritoneal dissemination including
      cytologically positive peritoneal lavage [CY(+)] than CA 125 or CA 19-9 in
      peritoneal lavage. The CEA level in peritoneal lavage as well as both serosal
      invasion and the CA 125 level in peritoneal lavage were significant factors for
      the prediction of peritoneal dissemination including CY(+) with a relative risk
      of 6.6, 14.1 and 9.4. In patients undergoing curative operations, the recurrence
      rate for peritoneal dissemination and liver metastasis in cases with CEA levels
      in peritoneal lavage of > or = 0.5 ng/ml was significantly higher than that in
      cases with CEA levels of < 0.5 ng/ml (p < 0.0001, p < 0.002). CONCLUSIONS: These
      finding suggest that the CEA level in peritoneal lavage is thus considered to be
      a predictor of peritoneal dissemination including CY(+).

PMID- 15459492
TI  - Single-agent gemcitabine in previously untreated elderly patients with advanced
      bladder carcinoma: response to treatment and correlation with the comprehensive
      geriatric assessment.
AB  - OBJECTIVE: The study aimed at evaluating the activity and toxicity of gemcitabine
      monochemotherapy in a unselected series of elderly patients with advanced bladder
      cancer. The secondary objectives were to establish whether there is a correlation
      between treatment and Comprehensive Geriatric Assessment (CGA) and, in addition,
      to determine overall patient survival. METHODS: Treatment consisted of six
      courses of chemotherapy with gemcitabine at a dosage of 1,200 mg/m2 on days 1 and
      8, every 21 days. CGA, as described by Gruppo Italiano di Oncologia Geriatrica,
      was assessed for evaluating the functional status of patients before, during, and
      after treatment. RESULTS: Twenty-five patients were enrolled (M/F 22/3), 22 of
      these were evaluable for response and 23 for toxicity. Characteristics of
      patients: median age 76 years (range 71-87); ECOG performance status (PS) 1 in 12
      patients and 2 in 13 patients; clinical stage III in 6 patients and IV in 19
      patients. At the end of the therapy the parameters of CGA improved in 4 cases
      (17%), remained unchanged in 17 cases (74%) and worsened only in 2 cases (9%).
      Two patients were not evaluable. Response evaluation showed 3 (13.5%) complete
      responses (CRs) and 7 (32%) partial responses (PRs), for an overall response rate
      of 45.5% [95% confidence interval (CI), 24.3-65.7%]. Three (13.5%) patients had
      stable disease (SD ) and 9 (41%) disease progression (DP). Median overall
      survival was 8 months and median time to progression was 5 months. Treatment was
      generally well tolerated, with 1 patient having grade 3 gastrointestinal toxicity
      and 3 having grade 4 neutropenia. CONCLUSIONS: We conclude that gemcitabine can
      be safely administered in monochemotherapy, is effective and does not worsen the
      functional status of elderly patients with advanced bladder cancer.

PMID- 15459493
TI  - Preoperative diagnosis and treatment results in 106 patients with uterine sarcoma
      in Hokkaido, Japan.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinicopathological features
      of uterine sarcoma in Hokkaido, Japan, between 1990 and 1999, and to identify
      prognostic factors of patients with such malignancies in this area and period.
      METHODS: One hundred and six patients with histologically proven uterine sarcoma
      were evaluated retrospectively. RESULTS: 93.5% of the patients with
      carcinosarcoma (CS) were diagnosed as having malignant disease preoperatively,
      while 65% of those with leiomyosarcoma (LMS) and 75% of those with endometrial
      stromal sarcoma (ESS) were preoperatively diagnosed as benign leiomyoma. When
      patients had no residual disease postoperatively, 5-year survival rates in
      patients with CS and LMS were 78.8 and 73.0%, respectively. ESS cases had a
      better prognosis (94.7% for stage I cases). In patients with early-stage sarcoma,
      pelvic lymphadenectomy and adjuvant chemotherapy, with or without cis
      diamminedichloroplatinum, failed to show a survival benefit in both CS and LMS
      cases. Distant metastasis, myometrial invasion, and no residual disease at
      surgery were significantly associated with risk of death or recurrence in CS and
      LMS cases. CONCLUSION: Accurate preoperative diagnosis of uterine sarcoma was
      difficult, and no residual disease at surgery was the most important prognostic
      factor in patients with this disease. Postoperative adjuvant therapy had little
      effect on survival, especially in early-stage disease.

PMID- 15459494
TI  - Single-agent epirubicin as primary chemotherapy in T2-T3, N0-N2, M0 breast
      carcinoma: 6-year follow-up.
AB  - OBJECTIVE: Single-agent epirubicin was tested as primary chemotherapy treatment
      in patients with early breast cancer >3 cm. METHODS: 100 women with locally
      advanced breast cancer >3 cm were treated with three cycles of single-agent
      epirubicin at a dose of 120 mg/m2. All patients showing tumor shrinkage to less
      than 3 cm were considered candidates for conservative surgery (quadrantectomy);
      in the remaining patients modified radical mastectomy was carried out.
      Postsurgical treatment consisted of CMF chemotherapy except for postmenopausal
      node-positive, estrogen-positive patients who were assigned to hormonal treatment
      with tamoxifen and postmenopausal node-negative, estrogen-positive ones who did
      not receive any treatment. RESULTS: Quadrantectomy was carried out in 71
      patients. At the median follow-up time of 69 months, the relapse rate was 29.6%
      among patients who underwent quadrantectomy (21 out of 71) and 58.6% among
      patients who underwent modified radical mastectomy (17 out of 29). CONCLUSIONS:
      Single-agent chemotherapy with anthracyclines could appear to be an effective
      treatment in inducing a tumor downstaging in patients with early breast cancer >3
      cm. This treatment can be administered outside clinical trials in patients who
      desire to preserve their body integrity. Further prospective, randomized trials
      are needed in order to validate and better define the role of epirubicin in the
      neoadjuvant strategy of breast cancer patients.

PMID- 15459495
TI  - Long-term follow-up of a pilot phase II study with neoadjuvant epidoxorubicin,
      etoposide and cisplatin in gastric cancer.
AB  - OBJECTIVE: The prognosis in T3-T4 or N+ gastric cancer is dismal, and the role of
      adjuvant therapy remains uncertain. Neoadjuvant chemotherapy could improve both
      resectability and survival. Here, we report the results of the long-term follow
      up of a pilot study aimed at evaluating a neoadjuvant treatment in a group of
      patients carefully staged by computed tomography (CT), endoscopic ultrasound and
      laparoscopy. METHODS: Twenty-five stage II-III patients with histologically
      proven gastric adenocarcinoma were enrolled in the study. All patients gave
      informed consent and were thoroughly staged. Patients were treated with
      epidoxorubicin (40 mg/m2 i.v.) on days 1 and 4, etoposide (VP-16; 100 mg/m2) on
      days 1, 3 and 4 and cisplatinum (80 mg/m2) on day 2, every 21-28 days for 3 pre
      operative cycles before CT clinical restaging followed by laparotomy and D2
      gastrectomy. Three further cycles of chemotherapy were planned after radical
      surgery. RESULTS: Twenty-four patients received the planned pre-operative
      chemotherapy and underwent surgical resection; total (13 patients) or subtotal (7
      patients) R0 D2 gastrectomy was possible in 20 patients. One patient died as a
      result of gastric bleeding. Perioperative complications occurred in 5 patients
      (failure of anastomosis in 1 patient and wound infection in the other 4). The
      pathologic response rate included 7 partial responses (29.1%) and 10 patients
      with stable disease (41.7%). The main toxicity was grade 3/4 neutropenia (68%),
      which occurred more frequently during the postoperative chemotherapy, and fatigue
      (68%). Fever or infection, however, were never observed. The median disease-free
      survival was 37 months, and median survival has not been reached after 40 months
      of median follow-up. One-, 2- and 3-year survival rates were 80, 64 and 60%,
      respectively. CONCLUSION: The notable long-term survival in the present study
      suggests a comparison between the neoadjuvant approach, including new drug
      combinations, and adjuvant chemo- or chemoradio-therapy in locally advanced
      gastric cancer.

PMID- 15459496
TI  - Association between components of the insulin-like growth factor system and
      endometrial cancer risk.
AB  - OBJECTIVE: The insulin-like growth factor (IGF) system has been related to cell
      proliferation, obesity, diabetes, hyperinsulinemia and endometrial cancer risk.
      We used data from a case-control study conducted in Italy to provide additional
      information on the relation between the IGF system and endometrial cancer.
      METHODS: A case-control study was conducted between 1999 and 2002 in Italy,
      including a total of 73 women with incident, histologically confirmed endometrial
      cancer and 108 controls admitted to the same hospital network for acute,
      nonneoplastic diseases. All subjects were interviewed using a validated
      questionnaire. RESULTS: The odds ratios for endometrial cancer comparing the
      highest versus the lowest tertile of various IGF components were as follows: 0.5
      [95% confidence interval (CI) 0.2-1.2] for free IGF-I, 1.1 (95% CI 0.5-2.6) for
      total IGF-I, 1.2 (95% CI 0.6-2.6) for total IGF-II, 2.4 (95% CI 1.0-5.9) for IGF
      binding protein (IGFBP)-1 and 0.8 (95% CI 0.4-2.0) for IGFBP-3. Further allowance
      for all IGF components in the model did not modify the results. The direct
      relation with IGFBP-1 was stronger and limited to heavier and older women.
      CONCLUSIONS: The present findings suggest a limited effect of the IGF system on
      endometrial cancer risk. Increasing IGFBP-1 levels seem to be associated with
      endometrial cancer risk in older women and in women with a higher body mass
      index.

PMID- 15459497
TI  - Prognostic relevance of altered pRb and p53 protein expression in surgically
      treated non-small cell lung cancer patients.
AB  - OBJECTIVE: The prognostic value of pRb and p53 altered expression in non-small
      cell lung cancer (NSCLC) remains debatable. We assessed the occurrence of altered
      pRb and p53 protein expression, and the prognostic value of these assays
      considered as separate and combined variables in operable NSCLC. The study group
      included 195 NSCLC consecutive patients from one institution who underwent
      curative pulmonary resection between 1994 and 1999. METHODS: Expression of pRb
      and p53 was assessed immunohistochemically with the use of monoclonal antibodies
      (LM95.1 and Pab 1801, Oncogene Science, respectively). RESULTS: A lack of pRb and
      abnormal p53 protein expression were found in 57 (29%) and 92 samples (47%),
      respectively, whereas both abnormalities (pRb-/p53+) occurred in 24 samples
      (12%). There was no relationship between altered pRb/p53 expression and major
      clinico-pathological characteristics, neither was there a significant difference
      in disease-free and overall survival between particular groups of patients with
      tumors carrying four possible pRb/p53 phenotypes. In uni- and multivariate
      analysis, the only variable associated with shortened disease-free and overall
      survival was stage of disease (p < 0.001) and degree of tumor differentiation (p
      = 0.005). CONCLUSION: These results suggest that altered pRb and p53 expression
      does not provide prognostic information in operable NSCLC patients.

PMID- 15459498
TI  - Clinicopathological significance of stromelysin-3 expression in colorectal
      cancer.
AB  - OBJECTIVE: Stromelysin-3 (ST3) is a member of the matrix metalloproteinases and
      suggested to play a role in tissue remodeling observed in growth and metastasis
      of tumors. ST3 overexpression in breast cancer is associated with a worse
      outcome. Our aims were to analyze ST3 expression in primary colorectal tumors and
      metastases, and further to identify relationships of the expression to
      clinicopathological factors. MATERIALS AND METHODS: ST3 expression was
      immunohistochemically analyzed in 200 primary colorectal adenocarcinomas and 36
      corresponding lymph node metastases. RESULTS: Scoring was performed by counting
      the percentages of positive cells and the percentages of positive areas. One
      hundred and one (51%) cases showed < or = 5% positive cells and 99 (49%) >5%
      positive cells. One hundred and two (51%) cases showed < or = 30% positive area
      and 98 (49%) >30% positive area. ST3 expression determined by both scoring
      methods was individually related to females, distally located tumors,
      infiltrative growth pattern and microsatellite stability. No relationship was
      found with age, Dukes' stage, differentiation and survival. CONCLUSIONS: These
      results suggest that ST3 protein was more involved in the pathway of colorectal
      cancer development in females, distal locations, infiltrative growth patterns and
      microsatellite stability.

PMID- 15459499
TI  - Prognostic significance of dysadherin expression in esophageal squamous cell
      carcinoma.
AB  - OBJECTIVE: Dysadherin is a cancer-associated cell membrane glycoprotein that has
      been reported to downregulate E-cadherin expression and promote metastasis. To
      evaluate the role of dysadherin in metastasis of esophageal squamous cell
      carcinoma (ESCC), we examined dysadherin and E-cadherin expression in patients
      with this cancer. METHODS: Dysadherin and E-cadherin expression was evaluated in
      117 ESCC patients (pT1, 31; pT2, 30; pT3, 39; pT4, 17) by immunohistochemistry.
      The findings were compared with the clinicopathological data of the patients.
      RESULTS: Both dysadherin and E-cadherin were localized to the cell membrane.
      Thirty patients (29.1%) had tumors positive for dysadherin and 41 patients
      (35.0%) had tumors positive for E-cadherin. Tumors showing dysadherin positivity
      and negative E-cadherin expression had a significantly worse prognosis than other
      tumors. When the patients with dysadherin- positive tumors were combined with E
      cadherin-negative patients, this group had a worse prognosis (p < 0.0001). Cox
      multivariate analysis revealed that dysadherin expression was an independent
      prognostic factor for ESCC (p = 0.003), but E-cadherin expression was not.
      CONCLUSION: Combined analysis of dysadherin and E-cadherin expression may help to
      predict the prognosis of patients with ESCC. Our results suggested that
      expression of dysadherin by this cancer may partly explain the poor prognosis of
      patients with preservation of E-cadherin expression.

PMID- 15459500
TI  - Loss of p16/CDKN2A protein in Epstein-Barr virus-associated gastric carcinoma.
AB  - We examined the expression of p16, the CDKN2A gene product, in EBV-associated
      gastric carcinomas (EBV-GCs). EBV-GCs were identified by detecting EBV-encoded
      small RNA (EBER) using an in situ hybridization assay of paraffin-embedded
      tissue. Two non-EBV-GC cases for each EBV-GC case were selected, matched for age,
      sex, tumor location, and depth of invasion. After excluding cases without
      sufficient tissue samples for immunohistochemical analysis, 54 EBV-GC and 117 non
      EBV-GC cases were available for the present study. The loss of p16 expression was
      more frequently observed in EBV-GCs (89%) than non-EBV-GC cases (32%; p < 0.001).
      Among non-EBV-GC cases, the loss of p16 expression was more frequent in female
      cases (57%) than male cases (29%) (p = 0.042). Expression of p16 was not related
      to the location of tumor, clinical stage of tumor, age, or prognosis of the
      patients. In conclusion, the present study suggests that the loss of p16-related
      cell cycle regulation may be associated with the development of EBV-GC.

PMID- 15459501
TI  - Inhibition of tumor metastasis by sodium caffeate and its effect on angiogenesis.
AB  - OBJECTIVE: Sodium caffeate (SC), the sodium salt of caffeic acid, was synthesized
      in our laboratory. We studied the antimetastatic effect induced by SC and its
      inhibition of tumor angiogenesis using various in vitro and in vivo metastasis
      assays. METHODS: The in vivo inhibitory effect of SC on metastasis and
      angiogenesis was examined in the Lewis lung carcinoma pulmonary metastasis model
      and chicken chorioallantoic membrane (CAM) model, respectively. MTT assay and
      flow cytometry were used to measure the inhibition by SC of the proliferation of
      transformed human umbilical vein endothelial cells (ECV304) and the apoptosis
      induced by SC in ECV304 cells, respectively. A cell attachment assay was used to
      evaluate inhibition by SC of the adhesion activity of human high metastatic giant
      cell carcinoma of the lung (PG) cells. A cell invasion assay was used to evaluate
      the effect of SC on the ability of PG cells to cross tissue barriers. Inhibition
      by SC of gelatinase secretion in PG cells was determined by zymography. RESULTS:
      In vivo results showed that SC (1 g/kg i.p. for 14 days) inhibited pulmonary
      metastasis at a rate of 55%. There were no differences in animal weights among
      the groups. The angiogenesis of CAM was inhibited by SC (200 microg/egg) at a
      rate of 70%. In vitro studies showed that SC inhibited the proliferation of
      ECV304 cells by inducing apoptosis. SC also reduced the adhesion and invasion
      ability of PG cells and inhibited the secretion of MMP-2 and MMP-9 in PG cells.
      CONCLUSION: SC might be a potential antimetastatic agent with an antiangiogenic
      effect.

PMID- 15459502
TI  - Epidemic West Nile virus encephalitis in Tunisia.
AB  - West Nile fever (WNF) is a mosquito-borne flavivirus infection. It is epidemic in
      Africa and Asia. In autumn 1997, a WNF epidemic occurred in the Sfax area
      (southeastern Tunisia). Fifty-seven patients were hospitalized with aseptic
      meningitis and/or encephalitis. Search for specific anti-West Nile virus (WNV)
      antibodies in serum and cerebrospinal fluid (CSF) was performed using an ELISA
      test. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect
      the WNV genome in CSF and brain specimens. Recent central nervous system (CNS)
      infection by WNV was confirmed in 30 patients, probable infection in 17 and it
      was excluded in 10. In the confirmed subgroup, patients with encephalitis were
      older than those with meningitis. CSF showed pleocytosis, high protein (47%) and
      normal glucose levels. Brain computed tomography-scan (CT-scan) and magnetic
      resonance imaging (MRI) were normal. RT-PCR disclosed WNV genome in the CSF in
      two cases and in a brain specimen in one. Three patients died rapidly, the
      remaining cases had favorable prognosis. Autopsy was performed in two cases and
      showed nonspecific lesions of encephalitis. No viral inclusions were seen with
      light microscopy. Seropositivity rate in patients' proxies for WNV was 23.4%.
      Prognosis of CNS involvement during WNF seemed to be poor in older patients. This
      is the first WNV encephalitis epidemic report in the Sfax area of Tunisia.

PMID- 15459503
TI  - Association between physical and cognitive function in healthy elderly: the
      health, aging and body composition study.
AB  - Performance measures of physical function (gait speed, chair stands, standing
      balance) and cognitive function [Teng-modified Mini-Mental Status Exam (3MS) and
      digit symbol substitution test (DSST)] were assessed at baseline in 3,075
      participants in the Health, Aging and Body Composition Study. Each physical
      function measure was examined for the strength and magnitude of association with
      cognitive function. All physical function measures were associated with both the
      3MS and DSST scores (p < 0.001), and in multivariate analysis each relationship
      was independent of demographic characteristics, weight, physical activity and
      comorbid health conditions of participants. The association of motor performance
      was consistently greater for the DSST than the 3MS and, among the motor tests,
      gait speed retained a significant association with both cognitive measures
      independent of demographic, weight, physical activity and comorbid health
      conditions. In this large cohort of high-functioning older adults, the
      correlation between physical and cognitive function was not entirely explained by
      demographics. Longitudinal studies are needed to determine the direction of
      causality in this relationship.

PMID- 15459504
TI  - Epidemiological study of Creutzfeldt-Jakob disease death certificates in Canada,
      1979-2001.
AB  - INTRODUCTION: A descriptive epidemiological analysis to update trends of
      Creutzfeldt-Jakob disease (CJD) deaths, from 1979-2001, was undertaken. METHODS:
      Cases with CJD as underlying cause were extracted. Age-adjusted death rates by
      age, sex, and province were calculated. Information on birthplace, autopsy
      indications and type of work were examined for death certificates from 1979 to
      1997. RESULTS: 462 cases were identified between 1979 and 1997. The average
      annual age-standardized mortality rate was 0.93 deaths per million persons during
      this period and 1.03 for 1998-2001. Persons 60 years or older demonstrated the
      highest average annual mortality rate. Rates were slightly higher among males and
      increased with age. Persons born in Canada accounted for 72% of deaths. Cause of
      death was verified by autopsy for 9.1% of patients while 21% of deaths indicated
      that additional information relating to underlying cause was expected. The
      service industry occupation represented the largest mortality (Quebec does not
      capture these data). CONCLUSIONS: Canadian rates are consistent with those of the
      United States and slightly higher than those of certain European countries.
      Approximately 44% of CJD cases had an autopsy record, though many were
      incomplete. We are unable to determine a relation with occupation. We recommend
      annual analysis of CJD death registrations for updated surveillance of trends, as
      mortality data are an efficient tool for monitoring incidence.

PMID- 15459505
TI  - Creutzfeldt-Jakob disease and cadaveric dura mater grafts in Japan: an updated
      analysis of incubation time.
AB  - The incubation time for 76 patients with cadaveric dura mater-transmitted
      Creutzfeldt-Jakob disease reported in Japan by November 2001 was analyzed to
      clarify its distributional feature and the risk factors which affect the earlier
      onset of the disease. Cluster analysis indicated that cases could be divided into
      3 clusters with respect to the incubation time, i.e., short (1.4-6.2 years),
      medium (7.0-11.9 years) and long (12.9-17.6 years). The incubation time in
      females was significantly shorter than those in males. Patients who were
      transplanted dura mater for facial spasms had a significantly shorter incubation
      time than those who received transplantation for other diseases including
      meningioma, aneurysm, or acoustic schwannoma. These results suggest that some
      host factors may have an influence on the incubation time of the disease.

PMID- 15459506
TI  - Seasonal patterns of incidence and case fatality of stroke in Malmo, Sweden: the
      STROMA study.
AB  - BACKGROUND: Studies on the temporal variation in stroke incidence have reported
      inconsistent results. Few have studied the temporal variations in case fatality.
      No study on incidence and case fatality of stroke by season in Sweden has been
      found. This study explores the weekly, monthly and seasonal variations in
      incidence and 28-day case fatality of stroke. METHODS: A total of 7,129 patients
      with first-ever stroke during the period 1989-1999 were retrieved from the Stroke
      Register of Malmo, Sweden. chi(2) test was performed to test the seasonal
      differences and Poisson regression analysis was used to calculate the case
      fatality ratios adjusted for sex and age. RESULTS: The stroke cases were on the
      whole randomly distributed over the study period of 4,017 days. Incidence of all
      types of stroke, intracerebral hemorrhage and subarachnoid hemorrhage showed no
      variation by season, month or weekday, but incidence of cerebral infarction for
      the total population was higher in autumn and winter. Twenty-eight-day case
      fatality (930 fatal events, 13%) clustered significantly over the study period.
      Winter emerged as the peak season among men (12.5%), women (17.2%) and total
      population (15.1%). No consistent variation of incidence and case fatality of
      stroke by month or weekday was found. CONCLUSION: Case fatality after stroke
      demonstrates a seasonal variation with a peak in winter. Incidence of stroke
      showed no consistent association with season, month or weekday.

PMID- 15459507
TI  - Seasonal variation in hospitalization and case fatality of subarachnoid
      hemorrhage - a nationwide danish study on 9,367 patients.
AB  - Seasonal variation in the occurrence of cerebrovascular disease has been
      reported, but data about subarachnoid hemorrhage (SAH) are few and inconclusive.
      We conducted a nationwide population-based study in Denmark to examine any
      seasonal pattern of hospitalization and case fatality of SAH. We identified 9,367
      patients with SAH and found a modest indication of overall seasonal variation for
      the risk of hospitalization with this diagnosis. The seasonal pattern, with the
      highest incidence in January and the nadir in July, was mostly apparent for
      subjects aged >65 years (peak-to-trough ratio = 1.18; 95% CI 1.04-1.32). There
      was little difference by sex. The overall 30-day case fatality rate was 38% and
      showed less seasonal variation. We found evidence of weak seasonal variation in
      hospitalization for SAH and almost no seasonal variation in a 30-day case
      fatality rate after SAH.

PMID- 15459508
TI  - No major birth order effect on the risk of multiple sclerosis.
AB  - In the present study, we found no association between multiple sclerosis (MS;
      definite and probable, n = 211) and birth order (p = 0.1411). The observed number
      of first-born patients did not differ significantly from the expected number (p =
      0.0871). While there was a significantly high birth order (n = 258, p = 0.0381)
      and a marginally significant low number of first-borns (p = 0.0475) when possible
      MS cases were included, an artefact due to the population structure may have
      accentuated this result. In comparison with the control birth cohort, there was
      no significant association with birth order (p = 0.0742) or the proportion of
      first-borns (p = 0.220) in a subgroup from the MS incidence cohort born between
      1915 and 1929 (n = 158). Birth order had no major impact on the risk of
      subsequent MS in this study.

PMID- 15459509
TI  - Cardiovascular risk factors and cognitive function in adults 30-59 years of age
      (NHANES III).
AB  - In the Third National Health and Nutrition Examination Survey (NHANES III), three
      measures of cognitive function [Simple Reaction Time Test (SRTT), Symbol Digit
      Substitution Test (SDST), and Serial Digit Learning Test (SDLT)] were
      administered to a half-sample of 3,385 adult men and nonpregnant women 30-59
      years of age with no history of stroke. We used multiple linear regression
      analysis to determine whether there was an independent association between
      performance on each cognitive function measure and defined hypertension (HTN)
      alone, type 2 diabetes mellitus (DM) alone, and coexistent HTN and DM after
      adjustment for demographic and socioeconomic variables and selected health
      behaviors. After adjustment for the sociodemographic variables, the combination
      of HTN + DM, but not HTN alone or DM alone, was significantly associated with
      worse performance on the SRTT (p = 0.031) and the SDST (p = 0.011). A similar
      pattern was observed for SDLT performance, but the relationship did not reach
      statistical significance (p = 0.101). We conclude that HTN in combination with DM
      is associated with detectable cognitive decrements in persons under age 60.

PMID- 15459510
TI  - Impact of age-related cerebral white matter changes on the transition to
      disability -- the LADIS study: rationale, design and methodology.
AB  - Age-related white matter changes (ARWMC) on brain MRI have been associated with
      cognitive, motor, mood and urinary disturbances. These factors are known to
      contribute to disability in elderly people, but the impact of ARWMC and of their
      progression on the transition to disability is not determined. The LADIS
      (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of
      ARWMC as an independent predictor of the transition to disability in initially
      nondisabled elderly (65-84 years). Subjects who are not impaired or impaired on
      only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting
      with different grades of ARWMC severity, were enrolled. Eleven European centers
      are involved. All the patients were assessed at baseline using an extensive set
      of clinical and functional tests including global functioning, cognitive, motor,
      psychiatric and quality of life measures. MRI studies were performed at baseline
      and will be repeated at the end of the follow-up period to evaluate changes of
      ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe
      using the scale of Fazekas et al. For each ARWMC severity class, the primary
      study outcome is the transition to disability defined as an impairment on 2 or
      more IADL scale items. Secondary outcomes are the occurrence of dementia,
      depression, vascular events or death. Six-hundred and thirty-nine subjects (mean
      age 74.13 +/- 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting
      and are being followed up for up to 3 years. The large and comprehensive set of
      measures in LADIS enables a comprehensive description of their functional and
      clinical features to be examined in relation to different morphological patterns
      and severity of ARWMC. The longitudinal design will give insight into the
      possible role of ARWMC and their progression as an independent contributor to
      disability in the elderly, eventually helping to develop preventive strategies to
      reduce the burden of disability in late life. The study results may also help to
      standardize, on an international basis, tools and criteria to identify early
      stages of disability.

PMID- 15459511
TI  - Education modifies the effect of alcohol on memory impairment: the third national
      health and nutrition examination survey.
AB  - We examined whether the relation of alcohol consumption to prevalence of verbal
      memory impairment was modified by education among 4,804 elderly subjects in the
      Third National Health and Nutrition Examination Survey. Verbal memory was
      assessed using delayed recall, with impairment defined as a combined score <4.
      Alcohol consumption over the previous month prior to the interview was assessed
      using a food frequency questionnaire. Prevalence of verbal memory impairment
      decreased from 11.3 to 7.2, 5.7, 5.1 and 4.4% in increasing categories of alcohol
      consumption (none, 1-4, 5-14, 15-30 and >30 drinks per month) in men, and from
      7.2 to 3.5 and 2.8% (for none, 1-14, and >14 per month) in women, respectively.
      Adjusting for age, race, and other factors, prevalence ratios of verbal memory
      impairment decreased with each increasing alcohol category, but the effect was
      attenuated when further adjusted for education. There was a much stronger
      protection from alcohol among subjects with more education: prevalence ratios
      were reduced from 1.0 to 0.2 to 0.1 for non-drinkers, 1-14, and >14 drinks/month,
      respectively (p for trend = 0.007). Our results suggest that alcohol intake is
      associated with a greater decrease in the prevalence of verbal memory impairment
      among more educated subjects than among those with less education, possibly
      related to differences in drinking patterns.

PMID- 15459512
TI  - Prevalence and incidence of multiple sclerosis in Las Palmas, Canary Islands,
      Spain.
AB  - OBJECTIVES: To determine the prevalence and incidence of multiple sclerosis (MS)
      in the city of Las Palmas (Canary Islands, Spain), geographically belonging to
      north-western Africa, but with European ancestry. METHODS: This population-based
      survey was conducted for a period of 5 years (1998-2002) in a Sanitary District
      of Las Palmas city (28 degrees 20' N), with a population of 82,623 inhabitants.
      Multiple sources were periodically investigated for case ascertainment. Patients
      with definite and probable MS were included. RESULTS: Sixty-four patients with MS
      were identified on prevalence day, December 31, 2002. According to Poser's
      criteria the crude prevalence rate was 77.5 per 100,000 (95% CI: 59.7-98.9). This
      rate decreased to 73.8 (95% CI: 56.5-94.8) according to McDonald's criteria. Age
      adjusted rates for the world and European standard populations were 61.6 (95% CI:
      47.1-78.9) and 70.6 (95% CI: 55-89), respectively. Prevalence was higher for
      women aged 25-44 years. In 17 patients onset of MS occurred within the study
      period. Average annual incidence was 4.1 per 100,000 (95% CI: 2.4-6.6).
      CONCLUSIONS: The prevalence and incidence rates in Las Palmas city are close to
      those reported from Continental Spain and other countries of southern Europe with
      similar social and ethnic background. These results highlight the role of racial
      ethnic factors in the genesis of MS.

PMID- 15459513
TI  - Brain abscess: a need to screen for pulmonary arteriovenous malformations.
AB  - BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) are direct connections
      between an artery and a vein in the pulmonary circulation associated with
      hereditary hemorrhagic telangiectasia in up to 88% of cases. Patients with PAVMs
      are at increased risk of brain abscess (BA). This study aimed to provide
      preliminary data on the prevalence of PAVMs among BA patients. METHODS:
      Administrative hospital discharge forms were used to identify patients with BA;
      possible PAVM patients were screened. RESULTS: 126 patients with BA were
      identified. Two patients had undiagnosed PAVMs at the time of admission for BA.
      The age-adjusted incidence of BA was 6.3 cases/1 million/year, with a male:female
      ratio of 2.0. CONCLUSION: Although PAVMs are rare conditions, they play a role in
      the development of BA. PAVMs are usually not recognized at the time of BA, thus
      exposing patients to life-threatening risks.

PMID- 15459514
TI  - Comparison of stroke risk factors and outcomes in patients with English-speaking
      background versus non-English-speaking background.
AB  - This study examined stroke risk factor profiles, management and outcomes for
      elderly patients with English-speaking background (ESB) and non-English-speaking
      background (NESB). This is an observational cohort study with both retrospective
      and prospective components. In total, 186 consecutive acute stroke patients aged
      > or =65 years admitted to our hospital were recruited over a 12-month period.
      Patient characteristics, stroke risk factors and management, in-hospital
      mortality, functional independence measurement scores before admission and at
      discharge, and discharge destination were recorded. On admission, NESB patients
      with atrial fibrillation (AF) were less likely to be taking warfarin than ESB
      patients (1 out of 19 with NESB vs. 19 out of 41 with ESB, p = 0.001). More NESB
      patients had a history of diabetes mellitus (DM) than ESB patients (41.4 vs.
      10.2%, respectively; p = 0.001). However, ESB and NESB patients were comparable
      in terms of age, gender, preadmission functional status as well as other stroke
      risk factors (including smoking and alcohol drinking pattern, prevalence of
      hypertension and lipid disorder) and their management. In-hospital mortality was
      similar between ESB and NESB patients (10.2 vs. 8.6%). In conclusion, we found an
      association with our population of elderly NESB patients and an underutilization
      of warfarin for AF as well as a higher frequency of DM. Determination of the
      underlying reasons for such differences may be of value in the primary health
      care of NESB patients.

PMID- 15459515
TI  - Frequency and risk factors of vascular cognitive impairment three months after
      ischemic stroke in china: the Chongqing stroke study.
AB  - BACKGROUND: Frequency of poststroke cognitive impairment is high in western
      countries, and the risk factors of poststroke cognitive impairment have not been
      fully understood yet. We sought to examine the frequency and risk factors of
      cognitive impairment after ischemic stroke in a large stroke cohort of China.
      METHODS: A total of 434 consecutive patients with ischemic stroke were enrolled.
      The cognitive status before and 3 months after stroke was evaluated using the
      Informant Questionnaire on Cognitive Decline in the Elderly and the Mini-Mental
      State Examination, respectively. Poststroke cognitive impairment was defined as
      cognitive impairment with concomitant stroke, stroke-related cognitive impairment
      was defined as cognitive impairment developing after index stroke, and cognitive
      impairment after first-ever stroke was defined as cognitive impairment developing
      after first-ever stroke. Logistic regression analysis was used to find the risk
      factors of cognitive impairment after stroke. RESULTS: (1) Frequency of
      poststroke cognitive impairment was 37.1%, that of stroke-related cognitive
      impairment was 32.2%, and that of cognitive impairment after first-ever stroke
      was 29.6%. (2) The patients with cognitive impairment more often had older age,
      low educational level, atrial fibrillation, prior stroke, everyday drinking, left
      carotid territory infarction, multiple lesions, embolism, and dysphasia. (3) The
      factors associated with poststroke cognitive impairment in logistic regression
      analysis were age (OR 1.215, 95% CI 1.163-1.268), low educational level (OR
      2.023, 95% CI 1.171-3.494), prior stroke (OR 5.130, 95% CI 2.875-9.157), everyday
      drinking (OR 2.013, 95% CI 1.123-3.607), dysphasia (OR 3.994, 95% CI 1.749
      9.120), and left carotid territory infarction (OR 2.685, 95% CI 1.595-4.521).
      CONCLUSIONS: Cognitive impairment is common 3 months after ischemic stroke in
      Chinese people. Risk factors for poststroke cognitive impairment include age, low
      educational level, everyday drinking, prior stroke, dysphasia, and left carotid
      territory infarction.

PMID- 15459516
TI  - Family history of stroke among Mexican-American and non-Hispanic white patients
      with stroke and TIA: implications for the feasibility and design of stroke
      genetics research.
AB  - Family history of stroke may differ by ethnicity. This study examined the
      associations of ethnicity and stroke risk factors with family history of stroke
      using data from the Brain Attack Surveillance in Corpus Christi Project. A random
      sample of stroke/transient ischemic attack cases was interviewed about family
      history of stroke (n = 524). Thirty-six percent of the cases reported a family
      history of stroke, with 26% reporting a parental and 13% a sibling history.
      Compared to non-Hispanic whites (NHWs), Mexican-Americans (MAs) were two times
      (OR = 2.07; 95% CI: 1.09-3.95) more likely to have a sibling with stroke. More
      MAs (8.1%; 95% CI: 4.6-11.6) had living siblings with stroke compared to NHWs
      (1.9%; 95% CI: 0.1-3.8). Since MAs are more likely to have living siblings with
      stroke compared with NHWs, MAs may be a more feasible population for family
      stroke studies than predominantly white populations.

PMID- 15459517
TI  - Familial prion diseases in the Basque Country (Spain).
AB  - In 1995, a surveillance system for prion diseases was set up in the Basque
      Country, an autonomous region in northern Spain (2.1 million inhabitants). In the
      period from January 1993 to December 2003, we diagnosed 21 patients with familial
      prion diseases prospectively and another 4 patients retrospectively. They
      represent 35% of all the cases referred to the epidemiological registry. Two main
      possible explanations for this unusual high incidence of familial prion diseases
      are proposed: first, comprehensive case ascertainment by public health
      neurologists; second, a probable cluster of the D178N mutation within families of
      Basque origin related to a still unconfirmed common ancestor. Further genetic and
      genealogical studies should resolve this issue.

PMID- 15459518
TI  - The short-term effects of physical therapy in different intensities of urodynamic
      stress incontinence.
AB  - PURPOSE: The aim of this study was to investigate and compare the short-term
      effects of a physical therapy program in patients with different intensities of
      urodynamic stress urinary incontinence (USI). SUBJECTS AND METHODS: 48 patients
      with USI were assigned to three groups according to the intensity of their
      incontinence: group I: 0-2 g (n = 17), group II (mild intensity: >2-10 g, n = 16)
      and group III (moderate intensity: >10 g, n = 15) as determined by the 1-hour pad
      test. A physical therapy program composed of Kegel exercises and interferential
      current was applied to all patients for duration of 5 weeks, with a total of 15
      sessions. The number of pads used a day, frequency of voiding (times/day), amount
      of urinary leakage according to the 1-hour pad test (mg), severity of complaint
      (as centimeters on visual analogue scale) and pelvic floor muscle strength (cm
      Hg) were evaluated. Pre-treatment and post-treatment values of these data were
      compared in each group and among groups. RESULTS: Analyses of the data indicated
      that the number of pads used a day, frequency of voiding and amount of urinary
      leakage decreased and pelvic floor muscle strength increased significantly in
      each group (p < 0.05). Cure in USI was found in 88% of subjects in group I and
      18% of subjects in group II (mild intensity). None of the patients in group III
      (moderate intensity) showed a cure effect. CONCLUSION: This physical therapy
      program was found to be more effective in mild and moderate intensities than
      severe USI.

PMID- 15459519
TI  - [Contraception and proception--competence of the gynaecologist in the planning of
      a woman's life].
AB  - Contra- and proception provoke different answers in our country and culture than
      globally speaking, particularly regarding non-industrialized nations.
      Contraception should be viewed as a means of preventive medicine, especially as a
      means of avoiding the psychosocial emergency of an unwanted pregnancy and
      potentially subsequent pregnancy termination. In this light, contraceptive
      counselling to teenagers is of particular importance. Reliable contraception does
      not cause a change of morals but supports and facilitates lifestyle and provides
      security. This aspect interacts closely with social and family politics. The
      integration of contraception into a woman's concept of life is decidedly
      dependent on these circumstances. The gynaecologist is a participant in the
      development of this concept, particularly for women who initially practice
      contraception, often in pursuit of a professional career, and later--often too
      late or perhaps never--bear an only child with maximal intention or potentially
      even after assisted reproductive medical intervention. The initially desired
      infertility frequently turns into the unfulfilled desire to bear children. The
      issues at hand are innovative social and sexual pedagogics that eliminate the
      separation between career and family. In the awareness of this pedagogic task,
      gynaecologists participate in the design of a woman's life concept as well as in
      the demographic change of society.

PMID- 15459520
TI  - [Vaginal hysterectomy leniens: intrafascial technique].
AB  - The appearance of a new intrafascial technique for vaginal hysterectomy serves to
      remind us that in spite of well-standardized techniques, gynecologists perform
      this less often than formerly. The described technique is an intrafascial
      variation of the extrafascial vaginal hysterectomy beginning at the fundus uteri.
      We mobilize the anterior vaginal wall using Strassmann's incision. The body of
      the uterus should be delivered through the anterior fornix. Then follows the
      ligation of the broad ligaments and careful dissection of the fibroareolar space
      of the posterior cervical wall. The cardinal ligament requires intrafascial
      clamping and ligation. This technique is simple and avoids injury to the ureters.
      If this operation is successfully performed, postoperative pain is minimal, and
      hospitalization could be greatly reduced.

PMID- 15459521
TI  - [Natural remedies during pregnancy and lactation].
AB  - Up to date there is a lack of systematically gathered data on the use of natural
      remedies (phytotherapeutic, homeopathic, anthroposophic, spagyric, Bach and
      Schussler remedies) during pregnancy and lactation. The aim of this non
      representative pilot study on 139 women, who came for delivery to three
      institutions between mid-1997 and the beginning of 1998, was to receive data
      about how often and within which spectrum natural remedies are used during
      pregnancy and lactation. During pregnancy 96% and within the lactation period 84%
      of the women consumed at least 1 natural remedy. Phytotherapeutic drugs were used
      most frequently. In contrast to the widespread use of natural remedies by
      pregnant women and nursing mothers in this study, little information on the
      effectiveness and possible risks is available. Therefore it seems necessary to
      examine and evaluate natural remedies used during pregnancy and lactation.

PMID- 15459522
TI  - [Wound rupture after Misgav-Ladach cesarean section: a case report].
AB  - INTRODUCTION: We describe a patient with wound rupture and burst abdomen after
      cesarean section with the Misgav-Ladach technique. CASE REPORT: A 33-year-old
      woman underwent primary cesarean section at 36 + 5 weeks gestation for a fetal
      indication. The procedure was done according to the Misgav-Ladach technique, i.e.
      the uterus was closed with a one-layer continuous locking stitch and the visceral
      and parietal peritoneal layers were left open. The rectus sheath was stitched
      with a continuous nonlocking stitch, the skin was closed with a continuous
      intracutaneous suture. On the seventh postoperative day, omentum was seen
      extruding from the skin incision. Reexploration showed that the suture of the
      rectus sheath had ruptured. The further postoperative course was uneventful.
      CONCLUSION: Although no general recommendations can be deduced from a single
      case, further reports on any complications of this technique will show whether it
      is as safe as believed until now.

PMID- 15459523
TI  - [Chemotherapy-associated enterocolitis--a rare but potentially lethal side effect
      of adjuvant breast cancer treatment: a case report].
AB  - ANAMNESIS: A 60-year-old patient underwent breast-preserving surgery for breast
      cancer of TNM stage pTla (m), pN2a (8/12), G2, pMO. After the operation, she
      received 4 cycles of epirubicin/cyclophosphamide (90/600 mg/m2), followed by 2
      cycles of docetaxel (100 mg/m2). Four days after the second cycle of docetaxel,
      the patient presented with abdominal pain, nausea, vomiting and obstipation of 3
      days' duration. FINDINGS: The physical examination showed a distended abdomen,
      absence of peristaltic sounds and pressure pain in the lower left abdomen. The
      laboratory examination was conspicuous for granulocytopenia of NCI grade Ill and
      an increased CRP concentration of 7.7 mg/dl. DIAGNOSIS: The main diagnosis was
      suspected chemotherapy-associated enterocolitis with signs of paralytic ileus;
      the latter was confirmed by computer tomography and laparotomy. THERAPY AND
      COURSE: Primary treatment consisted of placing a stomach tube, infusion therapy,
      broad-spectrum antibiotics and G-CSF. Later on, 5 explorative laparotomies with
      abdominal lavage were performed due to deterioration of the general condition and
      suspicion of intra-abdominal compartment syndrome. After a temporary improvement,
      the patient died of protracted multi-organ failure 8 weeks after hospitalization.
      CONCLUSION: Chemotherapy-associated enterocolitis is a very rare but potentially
      lethal side effect of cytostatic therapy. Therefore, gastrointestinal symptoms
      should be carefully noted in order to minimize the mortality risk by a timely
      therapeutic intervention.

PMID- 15459524
TI  - [Postmenopausal hormone therapy after WHI and HERS].

PMID- 15459525
TI  - [Recommendations for estrogen and progestin replacement therapy in climacteric
      and postmenopause. 31. Professional Meeting of the Zurich Discussion Circle,
      October 2003].

PMID- 15459526
TI  - [Recent aspects of gynecologic oncology. Report of the 40th Annual Congress of
      the American Society of Clinical Oncology, New Orleans, 5 - 7 June 2004].

PMID- 15459527
TI  - The histopathology of rosacea: 'where's the beef?'.

PMID- 15459528
TI  - Radiation-induced angiosarcomas.

PMID- 15459529
TI  - Rosacea: a clinicopathological approach.
AB  - BACKGROUND: There are few reports of the histological changes in rosacea, and
      little attempt has been made to correlate such changes with clinical findings. In
      the present study, we describe in detail the histopathological features of
      rosacea in a large number of patients and simultaneously investigate the
      aetiopathogenesis of the disease based on the comparative assessment of
      epidemiological, clinical and histological findings. METHODS: The study included
      73 patients with rosacea. A skin biopsy with a 4-mm punch was performed in each
      case. All biopsy specimens included subcutaneous tissue. In 10 randomly selected
      patients, facial biopsy specimens were obtained from both involved and uninvolved
      (non-lesional) skin. Demodex mite presence was estimated semi-quantitatively
      under light microscopy. Patients with self-reported gastro-intestinal symptoms
      were submitted to upper gastro-intestinal endoscopy, and a rapid urease test was
      performed. Serological antibodies, IgG and IgA, against Helicobacter pylori were
      also detected. RESULTS: The patients had a broad clinical spectrum of lesions. No
      specific histological features associated with either erythematous-telangiectatic
      or papulopustular clinical forms were noticed. Histological examination showed
      that there is no histological pattern unique to rosacea. Three different types of
      granulomas were observed: small palisaded ones around altered collagen and other
      granulomas of elastolytic and non-specific epithelioid type, all coexisting in 5
      cases. The deep dermis and subcutis were frequently involved. Comparative study
      in 10 rosacea patients between lesional and non-lesional skin biopsies revealed
      almost the same histological changes to the latter biopsies, to a lesser degree
      though. CONCLUSION: Rosacea seems to be a reaction pattern to which a variety of
      pathogenetic routes may lead.

PMID- 15459530
TI  - Mu-opiate receptor and Beta-endorphin expression in nerve endings and
      keratinocytes in human skin.
AB  - We have previously shown that human epidermal keratinocytes express a
      functionally active micro-opiate receptor, which adds a new dimension to the
      recently developed research in neuroimmunodermatology and neurogenic inflammation
      in skin diseases. Human keratinocytes specifically bind and also produce beta
      endorphin, the endogenous micro-opiate receptor ligand. Using confocal imaging
      microscopy, we could now demonstrate that micro-opiate receptors are not only
      expressed in keratinocytes, but also on unmyelinated peripheral nerve fibers in
      the dermis and epidermis. Some of the peripheral nerve fibers also express the
      ligand beta-endorphin. The keratinocytes positive for beta-endorphin staining are
      clustered around the terminal ends of the unmyelinated nerve fibers. Therefore
      the opiate receptor system seems to be crucial in the direct communication
      between nerves and skin. The keratinocytes can influence the unmyelinated nerve
      fibers in the epidermis directly via secreting beta-endorphin. On the other hand,
      nerve fibers can also secrete beta-endorphin and influence the migration,
      differentiation and probably also the cytokine production pattern of
      keratinocytes.

PMID- 15459531
TI  - Prevalence and risk factors for superficial fungal infections among Italian Navy
      Cadets.
AB  - BACKGROUND: Limited studies on the prevalence and risk factors for superficial
      mycoses are available. OBJECTIVE: The aim of this paper was to evaluate the
      prevalence and risk factors for superficial mycoses (dermatophytes and Candida
      spp.) in a sample of young Italian people resident at a military school. METHODS:
      A total of 1,024 young cadets from the Italian Navy Petty Officers School in
      Taranto, including 975 (95.21%) males and 49 (4.79%) females, mean age 22.5 +/-
      3.0 years (range 18-30), were consecutively examined by the same observer. A
      complete dermatological examination was performed on all the subjects, and skin
      scrapings for microscopy and fungal culture were obtained from suspected lesions.
      All the subjects completed a questionnaire providing information on sports
      practice, swimming-pool attendance, marching, wearing shower sandals, frequent
      use of 'gummed' shoes, history of severe traumas to the nails, presence of
      hyperhidrosis and history of superficial mycoses. The affected subjects were also
      asked if they were aware of their condition. Data were analysed by the
      Statistical Analysis System, version 8.0. The Fisher exact test and odds ratios
      were calculated. RESULTS: A total of 33 subjects (3.2%) were found to suffer from
      a mycologically confirmed fungal infection (3% by dermatophytes and 0.2% by
      Candida albicans): tinea pedis/Candida intertrigo of the feet was suspected in
      126 (12.1%) subjects and confirmed in 30 (2.9%), including 28 cases of tinea
      pedis and 2 cases of Candida intertrigo; tinea cruris/Candida intertrigo of the
      groin was suspected in 28 (2.7%) subjects, but confirmed in only 1 case (0.1%);
      onychomycosis was suspected in 64 (6.1%) subjects and confirmed in 2 cases
      (0.2%). The organism most frequently responsible in tinea pedis was Trichophyton
      mentagrophytes var. interdigitale (82.1%). The same species (50%) and T.
      mentagrophytes var. mentagrophytes (50%) were associated with tinea unguium,
      Epidermophyton floccosum was the only species detected in tinea cruris. Non
      dermatophytic filamentous fungi (Penicillium spp., Fusarium spp., Aspergillus
      spp. and Paecilomyces spp.), not considered pathogenic, were isolated in 48
      samples. None of the risk factors analysed were significantly associated with
      fungal infection. Only 2 subjects out of the 33 people affected were aware of
      their condition. They both had tinea pedis. CONCLUSION: The prevalence of mycoses
      in sailors living in an Italian military school was lower than rates detected in
      other military populations. This may be due to the cadets' lifestyle and
      environmental conditions. The most frequent infection was tinea pedis, mainly
      caused by T. interdigitale. None of the investigated risk factors were
      significantly associated with the disease, and most of the affected individuals
      were not aware of their condition.

PMID- 15459532
TI  - Revisiting the gender-linked melanoma burden.
AB  - BACKGROUND: Much is known about the worldwide rising incidence of skin cancers in
      the white populations. However, contradictory reports have been presented about a
      gender-linked risk for malignant melanoma (MM). OBJECTIVE: To review the recent
      epidemiological information about primary and metastatic MM in south-east
      Belgium. METHODS: Laboratory records of primary MM according to age and gender
      were compared per 3-year periods from 1988 to 2002. The numbers of MM per decade
      of patient age were corrected with regard to the number of citizens in the
      defined periods of age. This led to the calculation of the rate of estimated
      prevalence (REP). The same assessments were performed on 187 sentinel lymph node
      biopsies collected during the last 3-year period. RESULTS: A total of 1,051
      primary MM in women and 594 primary MM in men were diagnosed over the 15-year
      period. The female-to-male ratio rose by 24% over time, with a mean value of
      1.77. The most recent years showed a marked increase both in the numbers and REP
      of primary MM. This situation was present in both genders, although it was most
      prominent in women of the reproductive age. MM metastases were found in 38/187
      sentinel lymph nodes with a female-to-male ratio of 2.17. The age distribution
      for all sentinel lymph node biopsies copied that of primary MM, but the vast
      majority of the nodal metastatic MM was found in patients older than 50 years.
      The ratio between MM metastases and primary MM reached 6.1% (12/198) in men and
      6.9% (26/378) in women. CONCLUSION: A recent increase in primary MM incidence was
      observed in our laboratory. The most likely cause is ascribed to more sensitive
      MM detection using the combination of clinical dermoscopy and laboratory
      immunohistochemistry. During the past 15 years, women were more affected than men
      by both primary and metastatic MM. The gender difference in incidence of primary
      MM has progressively widened due to an increased incidence in young and middle
      aged women. By contrast, nodal metastatic MM mostly affected postmenopausal
      women.

PMID- 15459533
TI  - Finasteride treatment of patterned hair loss in normoandrogenic postmenopausal
      women.
AB  - BACKGROUND: Finasteride, an inhibitor of type 2 5alpha-reductase, inhibits
      conversion of testosterone to dihydrotestosterone, resulting in a decrease in
      serum and scalp dihydrotestosterone levels believed to be pathogenic in
      androgenetic alopecia. Oral finasteride has been shown to be effective in the
      treatment of hair loss in men, while its efficacy in women has remained
      controversial. METHODS: 5 postmenopausal women without clinical or laboratory
      signs of hyperandrogenism were given 2.5 or 5 mg/day oral finasteride for the
      treatment of pattern hair loss. Efficacy was evaluated by patient and
      investigator assessments, and review of photographs taken at baseline and at
      months 6, 12 and 18 by an expert panel. RESULTS: Finasteride treatment improved
      scalp hair by all evaluation techniques. The patients' self-assessment
      demonstrated that finasteride treatment decreased hair loss, increased hair
      growth and improved appearance of hair. These improvements were confirmed by
      investigator assessment and assessments of photographs. No adverse effects were
      noted. CONCLUSIONS: Oral finasteride in a dosage of 2.5 mg/day or more may be
      effective for the treatment of pattern hair loss in postmenopausal women in the
      absence of clinical or laboratory signs of hyperandrogenism.

PMID- 15459534
TI  - Cutaneous angiosarcoma arising in an irradiated breast. Case report and review of
      the literature.
AB  - Angiosarcoma (AS) is a rare, aggressive tumour of endothelial origin occurring in
      various clinical settings, including idiopathic AS on the head and neck in
      elderly people, lymphoedema-associated AS, post-irradiation AS, soft-tissue AS,
      and various others. Despite the widespread use of radiation therapy in the
      treatment of breast carcinoma, AS developing in the wake of a radiation therapy
      is extremely infrequent. Although there is little doubt that radiation in
      therapeutic doses can induce sarcomas, quantification of that risk is complicated
      by many variables, among them chronic lymphoedema. We describe a 70-year-old
      woman in generally good health who presented with a 2-year history of a maculo
      papular eruption on the skin of her right breast. There was no lymphoedema of the
      thoracic area. The lesions developed 3 years after she had undergone ipsilateral
      quadrantectomy for an invasive ductal carcinoma followed by 25 tangent field
      radiotherapy sessions on the breast. The oncological follow-up did not disclose
      local recurrence of the tumour or metastases of breast carcinoma. Histopathologic
      examination of a papule was diagnostic for AS. In addition, signs of chronic
      radiation dermatitis were found in the biopsy specimens. The patient underwent
      monthly cycles of chemotherapy with intravenous doxorubicin with partial
      remission of the affected area after 24 months, followed by the occurrence of
      liver metastases and exitus 30 months after diagnosis. From the review of the
      literature, it appears that post-irradiation mammary AS mainly affects women over
      60 who have undergone breast-sparing surgery and that it is usually associated
      with axillary lymphadenectomy. Whereas the role of lymphoedema does not seem
      relevant to the pathogenesis of this malignancy, the association with chronic
      radiation dermatitis in our case reinforces the supposed role of radiation in the
      development of this tumour. Onset of AS should be taken into consideration when
      treating patients who develop multiple lesions on the skin above the irradiated
      area, even many years after the therapy.

PMID- 15459535
TI  - Unilateral nevoid telangiectasia syndrome.
AB  - We report on a 29-year-old patient with a unilateral nevoid telangiectasia
      syndrome (UNTS). Based on microcirculation examinations, both functional
      impairments at the blood vessel level (laser-Doppler flowmetry) and
      morphologically altered capillaries (capillary microscopy) could be observed. We
      could demonstrate that microcirculatory examinations are suitable to demonstrate
      pathophysiological defects at the vascular level, especially since subclinical
      functional defects can also be recorded. To our knowledge, no such observations
      have yet been published with regards to UNTS.

PMID- 15459536
TI  - Detection of human papillomavirus type 58 in polydactylous Bowen's disease on the
      fingers and toes of a woman - concurrent occurrence of invasive vulval and
      cervical carcinomas.
AB  - The group related to human papillomavirus (HPV) type 16 (HPV-16, -31, -33, -35, 
      52, -58 and -67) is dominantly identified in cervical intraepithelial neoplasia
      and cervical carcinomas. HPV-16 has also been frequently detected in Bowen's
      disease on the hands and feet. We describe herein a case of polydactylous Bowen's
      disease on the fingers and toes of a woman who had had radical vulvectomy and
      hysterectomy for concomitant invasive vulval and cervical carcinomas. All the
      lesions, except for the lesions on the periungual side of her left index, middle
      and ring fingers, harbored HPV-58 DNA with more than 100 entire viral genome
      copies per cell detected by Southern blot hybridization. The histological
      localization of the viral DNA was confirmed in all the lesions by in situ
      hybridization. We could also retrospectively demonstrate HPV-58 DNA in her
      invasive vulval and cervical carcinoma tissues.

PMID- 15459537
TI  - Multiple myofibromas and an epidermal verrucous nevus in a child with
      neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 (NF1) is a common neurocutaneous autosomal dominant
      genetic disorder affecting primarily tissues derived from the embryonic neural
      crest. Two hallmark features of NF1 are the wide range of potentially affected
      tissues and the enormous phenotypic variability of disease traits even among
      patients from the same family. We present a boy fulfilling the diagnostic
      criteria for NF1 with two unusual lesions: infantile myofibromatosis and a
      verrucous epidermal nevus. To our knowledge this association has never been
      described before.

PMID- 15459538
TI  - Speckled lentiginous nevus syndrome: report of a further case.
AB  - A 42-year-old man had a large speckled lentiginous nevus on the left side of his
      trunk. The involved area was painful when touched and paresthetic. Moreover, the
      ipsilateral half of his body showed a pronounced hyperhidrosis. This case can be
      categorized as a typical example of speckled lentiginous nevus syndrome, a
      recently recognized phenotype characterized by a speckled lentiginous nevus of
      the papular type and ipsilateral neurological abnormalities in the form of
      dysesthesia, muscular weakness or hyperhidrosis. Speckled lentiginous nevus
      syndrome represents a mosaic phenotype. Most likely it originates from loss of
      heterozygosity occurring in a heterozygous embryo at an early developmental
      stage.

PMID- 15459539
TI  - Lymphogranuloma venereum - a rare cause of genital ulcers in central Europe.
AB  - Lymphogranuloma inguinale, caused by Chlamydia trachomatis serovar L1-L3 is rare
      in patients from western countries but needs yet to be considered in the
      differential diagnosis of genital ulcers. We report a case of a young male
      patient without any eventful travel history who presented with a genital ulcer at
      the sulcus coronarius and painfully enlarged lymph nodes in the right inguinal
      area. The typical clinical picture and serum IgM and IgG antibody titers of 1:16
      and 1:512, respectively, against C. trachomatis were suggestive of infection with
      C. trachomatis serovar L1-L3. The diagnosis was confirmed by isolation of the
      organisms from the ulcer ground and subsequent sequence analysis of the omp1 gene
      which led to identification of C. trachomatis genotype L2 with 99% homology to a
      reference strain of C. trachomatis serovar L2. The lesion healed rapidly under
      treatment with doxycycline for 3 weeks, and the lymph nodes did not ulcerate.
      Thus, clinical suspicion was confirmed by genotyping of the isolated strain
      allowing timely diagnosis and treatment of lymphogranuloma inguinale.

PMID- 15459540
TI  - Treatment of Pyoderma gangrenosum with low-dose colchicine.
AB  - Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown origin.
      Systemic agents occasionally administered provide either incomplete long-term
      control of the disease or have been associated with serious adverse side effects
      after chronic administration. We present two patients with PG successfully
      treated with low-dose colchicine. Antimitotic, anti-inflammatory and
      immunomodulating properties of colchicine might account for its beneficial
      effects in PG patients. Colchicine is effective and well tolerated in low doses
      by most patients. In addition, it is inexpensive and safer for long-term
      treatment than corticosteroids and other immunosuppressive agents. Colchicine may
      be proposed either as a single agent or as a corticosteroid-sparing agent for
      early treatment of PG.

PMID- 15459541
TI  - Bilateral Beau's lines and pyogenic granulomas following Guillain-Barre syndrome.

PMID- 15459542
TI  - Acute generalized exanthematous pustulosis induced by topical lindane.

PMID- 15459543
TI  - Minocycline hydrochloride injection therapy for ganglion and mucous cyst: a
      preliminary study.

PMID- 15459544
TI  - Nasal-type NK/T-cell lymphoma successfully treated with ProMACE-CytaBOM therapy.

PMID- 15459545
TI  - Tumoral calcinosis with cutaneous involvement in an elderly man.

PMID- 15459546
TI  - Topical tacrolimus in cutaneous lesions of dermatomyositis: lack of effect in
      side-by-side comparison in five patients.

PMID- 15459547
TI  - Alopecia areata induced by adjuvant treatment with alpha-interferon in malignant
      melanoma?

PMID- 15459548
TI  - NMR assignment of the chicken prion protein fragments chPrP(128-242) and chPrP(25
      242).

PMID- 15459549
TI  - [RGS proteins (regulators of G protein signaling) and their roles in regulation
      of immune response].
AB  - RGS proteins (Regulators of G-protein Signaling) comprise a protein family
      responsible for regulating G proteins. By enhancing the GTPase activity of the a
      subunit, they speed up the reconstruction of the heterotrimeric structure of G
      protein, thus inhibiting its signal transduction. Sst2 protein in yeast
      Saccharomyces cervisiae, FlbA in fungus Aspergillus nidulans, and Egl-10 in the
      nematode Caenorhabditis elegans are the first native G regulators with GTPase
      activity (GAPs:--GTPase-activating proteins). The existence of over 30 RGS human
      proteins has been confirmed thus far, and they have been grouped and classified
      into six subfamilies. In immunocompetent cells, RGS proteins are entangled in a
      complicate net of different interrelating signal pathways. They are connected
      with B- and T-cell chemokine susceptibility, efficient T cell proliferation, and
      the regulation of B cell maturation. They also take an essential part in
      inflammation. High hopes are held for drugs, which handle would be RGS proteins
      and which would further provide the possibility of modifying the pharmacokinetics
      of drugs acting through G protein- coupled receptors. The aim of this review is
      to discuss the new RGS protein family and explain the potential involvement of
      RGS proteins in the modulation of the immune response

PMID- 15459550
TI  - [Arginine--metabolism and functions in the human organism].
AB  - L-arginine plays important roles in the metabolism of an organism. It is the
      precursor for the synthesis of proteins and other molecules of great biological
      importance, including nitric oxide, ornithine, polyamines, agmatine, proline,
      glutamate, creatine, dimethylarginine, and urea. For young organisms arginine is
      an essential amino acid for optimal growth and development, and must therefore be
      provided in the diet. For adults, arginine is a conditionally essential amino
      acid, especially in such conditions as trauma, burn injury, small-bowel
      resection, and renal failure. L-arginine administration improves cardiovascular,
      pulmonary, immune, and digestive functions and protect against the early stages
      of cancerogenesis.

PMID- 15459551
TI  - [Chemical structure and biosynthesis of lipopolysaccharide--important component
      of the cell envelope of Gram-negative bacteria].
AB  - The outer membrane is the first layer of the cell envelope of Gram-negative
      bacteria. This fragment of the cell envelope is built of phospholipids in the
      internal part and mainly of lipopolysaccharides in the external part.
      Lipopolysaccharide (LPS, endotoxin) is a thermostabile component consisting of
      three parts which differ in chemical structure and biological activity. LPS
      contributes greatly to the structural integrity of bacteria and protects them
      from host immune defenses. This review explains what makes this LPS leaflet an
      effective barrier to permeability and describes the pathways of biosynthesis and
      the assembly of the hydrophobic domain, known as lipid A, a core oligosaccharide,
      and the distal polysaccharide (O-antigen).

PMID- 15459552
TI  - [Role of vitamin C in oxidative DNA damage].
AB  - Vitamin C (ascorbic acid) has considerable antioxidant activity: it scavenges
      reactive oxygen species and may, thereby, prevent oxidative damage to important
      biological macromolecules, such as DNA, proteins, and lipids. Data concerning the
      influence of vitamin C on oxidative DNA damage are conflicting and some of the
      discrepancies can be explained by the different experimental methodologies
      employed. Data using biomarkers of oxidative damage of DNA bases in human
      lymphocytes in vitro have provided no compelling evidence to conclude that
      vitamin C supplementation can decrease the level of oxidative DNA damage. There
      are also no conclusive data from studies of strand breaks for a protective effect
      of ascorbic acid. The consumption of food rich in vitamin C (fruits and
      vegetables) appears more protective because it exerts more positive effects in
      decreasing oxidative DNA damage to human cells. Recent studies indicate that
      vitamin C is much more than just an antioxidant; it regulates the expression of
      some genes participating in apoptosis or DNA repair processes. The purpose of
      this review is to provide a summary of the role of vitamin C in oxidative DNA
      damage.

PMID- 15459553
TI  - [Anaerobic intestinal microflora in pathogenesis of autism?].
AB  - The present study provides information on differences in the gastrointestinal
      microflora of children with autism compared with a control group. Special
      attention was paid to the microbiological characteristic of the new obligate
      anaerobic microorganisms: Clostridium bolteae sp.nov. and Cetobacterium somerae
      sp.nov. observed in stools of children with autism. In light of recent
      publications, the hypothesis of interactions between intestinal microflora - and
      the brain based on possible alterations in bacterial toxins and other metabolites
      in the pathogenesis of autism is discussed.

PMID- 15459559
TI  - [Role of radiotechnologists in mammography screening for breast cancer].

PMID- 15459560
TI  - [Ethics in education for radiological technologists].

PMID- 15459561
TI  - [Diagnosis of uterine, ovary and fetal diseases by ultrasonography].

PMID- 15459563
TI  - [Report on the 60th Congress of Japanese Society of Radiological Technology].

PMID- 15459562
TI  - [Report on the 60th Congress of Japanese Society of Radiological Technology].

PMID- 15459564
TI  - [MRI technological conference in Kansai].

PMID- 15459565
TI  - [X-ray Protection Construction Standardization Manual -Part 4-].

PMID- 15459566
TI  - [Development of small adenocarcinoma phantoms for comparison of image quality
      among various chest X-ray systems].
AB  - The aim of our study was to develop a phantom of lung adenocarcinoma for use in a
      comparative evaluation of image quality among various chest X-ray systems. In
      this study, we developed type A, B, and C phantoms of lung adenocarcinoma
      according to Noguchi's classification. The shape of lung adenocarcinoma was
      assumed to be spherical with a different density in the core. The shapes of the
      phantoms were obtained by calculating equivalent thickness to X-ray transmission,
      leading to the same shadow as the sphere in order to perform practical visual
      evaluation using a chest lung phantom to which the phantoms were attached. The
      phantoms were tough water phantoms made by Kyoto Kagaku Co., Ltd. The performance
      of the phantoms was validated for chest radiographs of the phantoms attached to
      the surface of the chest lung phantom. The results of visual evaluation of tumor
      detectability by 13 radiologists and technicians showed generally good agreement
      with previous clinical data.

PMID- 15459567
TI  - [Newly developed monitor for IVR: liquid crystal display (LCD) replaced with
      cathode ray tube (CRT)].
AB  - For physicians who monitor images during interventional radiology (VR), we have
      built and been using a system that employs a liquid crystal display (LCD) instead
      of the conventional cathode ray tube (CRT). The system incorporates a ceiling
      suspension-type monitor (three-display monitor) with an LCD on each of the three
      displays for the head and abdominal regions and another ceiling-suspension-type
      monitor (5-display monitor) with an LCD on each display for the cardiac region.
      As these monitors are made to be thin and light in weight, they can be placed in
      a high position in the room, thereby saving space and allowing for more effective
      use of space in the X-ray room. The system has also improved the efficiency of
      operators in the IVR room. The three-display folding mechanism allows the
      displays to be viewed from multiple directions, thereby improving the environment
      so that the performance of IVR can be observed.

PMID- 15459568
TI  - [Basic evaluation of a new technique, tailored contrast truck-fluid-attenuated
      driven inversion-recovery (TACT-FLADIR), to attenuate the signals of both
      cerebrospinal fluid and inflow artifacts].
AB  - The aim of the present study was to evaluate the new tailored contrast truck
      fluid-attenuated driven inversion-recovery (TACT-FLADIR) sequence. Technically,
      this sequence uses a nonselectively driven inversion (DI) pulse as the inversion
      pulse. The DI pulse has two parameters, number of refocus pulses (NR) and
      preparation time (TP). Using normal volunteers, we optimized NR and TP to measure
      signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) of gray matter
      (GM) and white matter (WM), and to obtain CSF inflow artifacts. TACT-FLADIR was
      compared with conventional FLAIR using volunteers and patients. Among the
      optimized parameters, SNR and CNR were dependent on TP, and inflow artifacts were
      reduced by increasing NR. In brain imaging, TACT-FLADIR provided improvement in
      both SNR and CNR compared with conventional imaging with suppressed CSF signal
      and saturated flow artifacts.

PMID- 15459569
TI  - [Preliminary study on automated detection of cerebral vessels from head CTA
      images].
AB  - We propose an approach for automated detection of cerebral vessels from head CT
      angiographic images. This approach contains two major features. First, instead of
      using the well-known image-processing techniques such as thresholding and
      labeling, a novel Laplacian-like filter is developed and employed in the region
      of interest in an image to be processed. Second, not only is the axial-view image
      reconstructed from head CT angiographic images used, but, in addition, the
      sagittal- and coronal-view images are reconstructed and used. By applying these
      major features in the process of detection of brain vessels, more accurate
      results can be achieved. To validate the effectiveness of the proposed method, we
      applied the method to three clinical cases, all of which were head CT angiograms.
      Our preliminary results showed that the proposed method has the potential to
      automatically detect cerebral vessels in head CT angiograms with acceptable
      accuracy.

PMID- 15459570
TI  - [Average glandular tissue dose and image quality in screen-film mammography].
AB  - We investigated the relationship between average glandular tissue dose and
      imaging properties such as image density, contrast, and visual image quality,
      varying the tube voltage and subject parameters (glandular fraction and breast
      thickness) The wax inserts of 156 phantom and disk of polymethyl methacrylate
      (PMMA) were arranged between the BR-12 breast-equivalent phantoms. These phantoms
      were radiographed using automatic exposure control (AEC) for the various
      combinations of tube voltage and subject parameters. In addition, exposures were
      measured at the same time. The results showed that the average glandular tissue
      dose increased when the high glandular fraction and/or thick phantom were being
      radiographed with the low tube voltage. We found that the criteria of the
      Japanese Mammography Screening Accreditation Program for image quality were not
      satisfied when breast thickness was greater than 6 cm.

PMID- 15459571
TI  - Pharmacologic therapy for the treatment of asthma in children.
AB  - Asthma in children results in a large negative global impact and its recent
      increase in prevalence demands an aggressive and comprehensive treatment program.
      Recently there has been increasing global cooperation for developing more
      standardized treatment plans to address this complex disease. Advances in our
      knowledge of the exact mechanisms of this disease continue to lead to better
      pharmacologic treatment options. A variety of medications are currently available
      for the treatment of both acute and chronic asthma symptoms. The importance of
      controller medications that affect the underlying inflammatory process has been
      emphasized in the most recent treatment recommendations. The initial choice of
      medications for asthma treatment is frequently based on the severity
      classification of the asthma symptoms. Severity classifications include mild
      intermittent, mild persistent, moderate persistent, and severe persistent.
      Guidelines for treatment options for each of these severity classifications are
      available which incorporate appropriate flexibility for such a dynamic disease.
      These guidelines are based on evidence of effectiveness, relative safety, and
      other factors. This article reviews many of these medications, their actions,
      side effects, relative efficacy, and their indications for pediatric asthma
      treatment.

PMID- 15459572
TI  - Anti-IgE therapy in children with asthma.
AB  - The prevalence of asthma continues to grow rapidly among children in areas
      undergoing urbanization. Current pharmacotherapy for asthma reduces inflammation
      and provides symptomatic relief, but it does not work for all patients and it
      does not entirely suppress the underlying disease. For these reasons new
      therapeutic approaches are still needed. Anti-IgE, the newest therapeutic
      modality for asthma, a biologic agent to control allergic disorders, represents a
      fundamentally new concept in treatment.

PMID- 15459573
TI  - Antibiotics for otitis media with effusion.
AB  - Otitis media with effusion (OME) is defined as asymptomatic middle-ear effusion,
      that is, without the signs and symptoms of acute otitis media (AOM), such as
      fever, otalgia, or otorrhea. OME can occur after an episode of AOM or may occur
      without any prior or concurrent symptoms and is often noted on a routine physical
      examination or screening. Because children with OME are usually not ill, there is
      a question of whether treatment is warranted for this condition. Also adding to
      the complexity of this problem is the high spontaneous cure rate of OME. This
      paper will review the many clinical trials of the efficacy of antimicrobial
      therapy for OME. We have grouped the studies into 4 major categories: antibiotic
      vs no treatment, antibiotic vs placebo, antibiotic vs antibiotic, and antibiotic
      prophylaxis. While study designs, definitions, and quality vary widely, these
      studies show a trend toward short-term efficacy of antimicrobial treatment, but
      long-term efficacy is doubtful. In this age of antimicrobial resistance, coupled
      with the high natural cure rate, routine antimicrobial treatment of OME is not
      warranted. It may be useful in selected patients, particularly those with chronic
      OME (3 months or longer of bilateral effusion or 6 months or longer of unilateral
      effusion) for whom surgery is being considered: a 1-time short course of
      antibiotic may allow cancellation or at least postponement of a surgical
      procedure, particularly in spring/summer when one would like to avoid placing
      tubes in the ears and placing the child at risk for otorrhea due to water
      exposure. Also, antimicrobial therapy may provide at least short-term relief for
      symptomatic children (hearing loss, developmental delay, etc.) for whom surgery
      must be postponed or is contraindicated.

PMID- 15459574
TI  - Interventional uroradiology in paediatrics: a potpourri of diagnostic and
      therapeutic options.
AB  - The objective of the present work is to describe the indications and application
      of interventional, image guided diagnostic and therapeutic procedures in the
      paediatric urinary tract. The different indications and techniques are listed and
      illustrated, comprising most established indications such as percutaneous
      nephrostomy, sonographic guided renal biopsy, and interventional evaluation as
      well as treatment of childhood renal vascular disease. Additionally, some newer
      applications such as echo-enhanced urosonography, interventional treatment of
      urinary tract stenosis, or sonographically guided catheterism for deployment of
      therapeutic agents are included. Though the procedures are safe and successful in
      general, complications may occur, and peri- and post-interventional monitoring is
      mandatory to insure early detection and adequate management. Sometimes additional
      treatment or a 2nd procedure may become necessary. In conclusion, though rather
      seldom indicated, image guided interventional procedures are performed
      successfully for diagnosis and treatment of a variety of diseases of the
      paediatric urinary tract. They can be considered a valuable additional modality
      throughout infancy and childhood that should be performed by skilled and well
      trained paediatric radiology staff at specialised referral centres.

PMID- 15459575
TI  - [Transfusions in paediatric emergencies].
AB  - The interest in pathological emergencies and their therapeutical options has
      underscored the need for immediate, precise and evidence based criteria in the
      administration of blood products. In fact these often are an extremely important
      therapeutical option, above all for children less than 3 years old. Therefore our
      work pointed out a precise and easy to follow diagnostic and therapeutic
      alghoritm as already done for other clinical emergencies. We tried to supply all
      the indications for the correct use of whole blood, red packed cells, platelets,
      granulocytes, plasma and albumin. This alghoritm includes the history, the
      ethiological and clinical aspects, the domiciliary interventions, the indications
      to the admission, the diagnostic investigations, the therapeutical aspects and
      the indications to the discharge. Starting from our assigned aims and following
      the above mentioned alghoritm, we also try to give some practical updated and
      evidence based hints to face the difficult situations arisen by the anxious
      attentions of the relatives. In fact these can sometimes be cause of mistakes.
      Medicine is, however, a ever changing science. The new knowledges and
      technologies and the changes according to the new acquisitions are at the basis
      of the continuous development of new diagnostic and therapeutical approaches. Our
      aim was therefore to provide a state of art in this field using the data
      published in the most recent and authoritative literature.

PMID- 15459576
TI  - [Urinary tract infections: review of the case records of the 5-year-old
      population of Novara].
AB  - AIM: A feverish high temperature is the symptom that most frequently leads
      families to take their children to a Pediatric First Aid unit. In the
      differential diagnosis of the causes of hyperpyrexia the presence of infections
      of the genito-urinary tract have to be excluded. Infections of the urinary ways
      are often the cause of high temperatures in infancy, particularly during the 1st
      year of life; early identification at the moment of examination at the Paediatric
      First Aid clinic of patients with infections of the urinary ways makes it
      possible to prevent the onset of renal complications. We carried out a
      retrospective study with the purpose of evaluating the incidence of infections of
      the urinary ways and their complications in paediatric patients who had come to
      the First Aid unit for hyperpirexia and were later hospitalised after examination
      of the urine revealed and infection of the urinary ways. METHODS: The study was
      carried out by consulting the registers listing arrivals at the First Aid unit
      and the subsequent discharge diagnosis. We then consulted the clinical records of
      patients who required admission to our Paediatrics Clinic arter the first aid
      examination. RESULTS: Re-reading the registers of examination carried out and the
      clinica records of hospitalised patients there emerged an increase in the
      observation of this pathology, diagnosed at the moment of the First Aid
      examination by means of rapid tests and thereafter assessed by haematochemical
      and radiological tests. CONCLUSIONS: In our opinion this increase could be
      attributed to the greater attention paid to diagnosing the causes of fever of
      apparently unknown origin.

PMID- 15459577
TI  - Retrospective analysis of post-hemorrhagic ventricular dilatation in very low
      birth weight infants, short and long-term outcome.
AB  - AIM: The aim of this paper was to study the evolution of ventriculomegaly, the
      treatment and the developmental problems of a group of very low birth weight
      infants (VLBWI) born between 1985 and 1999 who met Levene's percentiles for post
      hemorrhagic ventricular dilatation (PHVD). METHODS: A retrospective hospital
      based study of a cohort of 66 VLBWI who fulfilled the diagnostic criteria for
      PHVD was performed. Measures of neurodevelopmental outcome were evaluated by
      analyzing neurosensorial patterns as well as mental and behavioral adjustment up
      to pre-school age in 35 survivors. RESULTS: The PHVDs initially (1985-1989) were
      due to a grade 4 intraventricular hemorrhage (IVH) (71.4%), and in the latter
      period (1995-1999) to IVH grade 2 (36.4%), grade 3 (31.8%) and grade 4 (31.8%).
      Acetazolamide has been used since the 90's in neonates with progressive PHVD. The
      90s were characterized by an increasing incidence of tiny babies and rapidly
      progressive PHVD. Taps were more frequent in the arrested dilatation group.
      Similarly, taps and acetazolamide were administered to newborns with persistent,
      slowly-progressive ventricular dilatation (PHVD > 4 weeks). The highest
      correlation was found for gestational age with the mental and psychomotor
      developmental indexes. Delayed performance and/or mental retardation were
      diagnosed in 71.4% of the survivors. CONCLUSION: Acetazolamide and lumbar
      puncture, associated with other risk variables (severity of IVH, PHVD evolution
      and associated parenchymal lesions) are harmful in terms of development, but they
      have a role in the short-term arrested and slowly progressive PHVD of the
      surviving babies, and not in the mortality incidence. Our retrospective data
      demonstrated that lower gestational age at birth increased the risk of lower
      mental and psychomotor developmental indexes.

PMID- 15459578
TI  - [Value of skin prick test and atopy patch test in mite-induced respiratory
      allergy and/or atopic eczema/dermatitis syndrome].
AB  - AIM: The atopy patch test (APT) was introduced to assess sensitization to
      inhalant allergens in patients with atopic/eczema dermatitis syndrome (AEDS), but
      its diagnostic role in subjects with respiratory allergy is scantly investigated.
      We sought to evaluate the response to APT and to skin prick tests (SPT) with mite
      extracts in subjects with persistent respiratory symptoms (rhinoconjunctivitis,
      rhinosinusitis, asthma), with AEDS, and with both the diseases. METHODS: Eighty
      nine patients were included in the study, 75 (84.3%) children and 14 (15.7%)
      adults, 54 (60.7%) males and 35 (39.3%) females (median age 5.4 years). They were
      divided in 3 groups, respectively formed by 47 (mean age 12.3+/-11.6 years), 15
      (mean age 2.2+/-2.5 years), and 27 (mean age 6.2+/-6.3 years) subjects, according
      to the presence of only respiratory symptoms, only AEDS, or both, and underwent
      to usual SPT with mite extracts and to APTs done by mite extract in Finn chambers
      and removed after 48 hours, with readings after 20 minutes and 24 hours. RESULTS:
      Of the 89 patients, 24 showed a positive SPT and 69 a positive APT; in 17 both
      SPT and APT were positive, while 13 were negative to the 2 tests. The APT was
      more frequently positive than SPT not only in the 2 groups with AEDS -- 32/42
      (86.5%) vs 8/42 (21.6%) -- but also in the group with only respiratory symptoms -
      37/47 (78.7%) vs 16/47 (34%). CONCLUSION: These results confirm the high value
      of APT in patients with mite-induced AEDS and suggest that its routine use might
      improve also the diagnosis of respiratory allergy to house dust mites.

PMID- 15459579
TI  - [Poisoning in first year of age. A multicentre study].
AB  - AIM: The aim of this study is to describe clinical and epidemiological features
      of toxic exposures in children under 1 year. METHODS: During 2001 a prospective
      study on poisoning was carried out in the Pediatric Emergency Departments (ED) of
      14 hospitals. Information stored concerned epidemiological and clinical features,
      evaluation of accidental or deliberate manner of exposure as well as of clinical
      consequences. Data were compared with those registered in 1-4 year-old patients.
      RESULTS: During 2001 out of 1,026 children registered, 111 (10.8%) were under 1
      year. Exposure occurred exclusively at home and by accident. As compared to 1-4
      year-old patients, children exposures were more frequently due to parental errors
      (38.7% of cases vs 7.3%), and involved plant poisons (22.5% vs 7.3%). In 1/3 of
      these cases the cause was due to non-toxic exposures, in another 1/3 an early
      treatment avoided clinical consequences. In the other cases, symptoms were of low
      to moderate severity, only in 1 case they were serious. No deaths occurred. One
      out of every 3 children was admitted, the others were sent home directly from ED
      (23.4%) or after a short observation period (44.1%). CONCLUSION: The increase in
      poisoning in children under 1 year, as compared to previous multicentre studies,
      is deserving of concern. In spite of the relatively low severity they are
      completely preventable. The study shows that information on poisons prevention
      for parents needs to be improved to prevent exposure of children under 1 year to
      toxic substances at home.

PMID- 15459580
TI  - Facial anomalies in patients with cytochrome-c-oxidase (COX) deficiency: a
      dysneurulation.
AB  - The authors report 3 cases of cytochrome-c-oxidase deficiency (2 cases of Kearns
      Sayre syndrome and 1 case of chronic progressive external ophthalmoplegia) with
      Central Nervous System alterations and facial anomalies. The facial anomalies are
      high forehead, wide nasal bridge, upturned nose, long and flat philtrum
      (alterations depending on frontal-nasal-premaxillary structures which derive from
      prosencephalic neural crests), hypoplastic maxilla and mandible, ophthalmoplegia
      (alterations of maxilla and III-VI cranial nerve nuclei, which derive on the
      mesencefalic neural crests), low set ears, short neck (alterations of the 3rd,
      4th branchial arch derivatives, which arise from rhombencephalic neural crests).
      The authors conclude that cytochrome-c-oxidase deficiency in embryonic stage can
      injure, in Kearns-Sayre syndrome and chronic progressive external
      ophthalmoplegia, distal tissues of face and Central Nervous System depending on
      neural crests, and that the symptomatology of these diseases can be ascribed to
      dysneurulation.

PMID- 15459581
TI  - Perforated appendicitis presenting as incarcerated hernia.

PMID- 15459582
TI  - Approach to the management of diabetic patients with heart failure: role of
      thiazolidinediones.
AB  - Diabetes mellitus is a chronic, progressive disease that results in microvascular
      and macrovascular complications. Patients with diabetes are at high risk for
      developing heart failure, and the prevalence of diabetes in patients with heart
      failure ranges from 24% to 44%, with an estimated 1 to 2 million individuals in
      the United States having both diabetes and heart failure. Patients with diabetes
      and heart failure are at increased risk for mortality. Primary treatment goals in
      diabetes include restoration and maintenance of normoglycemia, avoidance of
      diabetic complications, and prevention of cardiovascular events. The range of
      therapeutic options for glycemic control has been extended with the introduction
      of thiazolidinediones (TZDs) used as monotherapy or in combination with other
      oral antidiabetic medications or insulin. TZDs decrease plasma insulin levels,
      improve endothelial function, decrease vascular inflammation, and decrease C
      reactive protein levels, effects that are potentially beneficial in patients with
      heart failure. Weight gain and peripheral edema are recognized side effects of
      these drugs, particularly when used in combination with insulin. Although health
      care providers should be aware of the potential risk of worsened heart failure
      when TZDs are used in patients with diabetes and heart failure, these agents may
      be considered for use in patients with New York Heart Association class I and II
      heart failure when appropriate monitoring can be provided. Prospective clinical
      trials are currently under way to further define the cardiovascular safety and
      efficacy of TZDs in diabetic patients with heart failure.

PMID- 15459583
TI  - Surrogate end points for pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension is a rare disease that is characterized by
      increased pulmonary vascular resistance and right heart failure. Recent advances
      in the understanding of pulmonary arterial hypertension have been translated into
      effective therapies tested in clinical trials. These trials have used surrogate
      end points as the primary outcomes of interest. However, it is not clear which
      potential surrogate end points are reliable and valid for studying pulmonary
      arterial hypertension. Identification of suitable end points not only would help
      investigators design appropriate clinical trials but would assist clinicians in
      caring for this patient population. Hemodynamic, echocardiographic, neurohormone,
      and exercise measures hold some promise as potential surrogate end points for
      clinical trials of therapy for pulmonary arterial hypertension. Hemodynamic
      measures have the most evidence to support their use. Functional studies, such as
      the distance walked in 6 minutes, also may be meaningful. We present the
      available data as well as the strengths and weaknesses of each metric. Further
      studies should focus on validating the most promising of these surrogate end
      points, so that future investigators, subjects, and patients may benefit from the
      advantages they confer on clinical trials and patient care.

PMID- 15459584
TI  - Outcome of ST-elevation myocardial infarction treated with thrombolysis in the
      unselected population is vastly different from samples of eligible patients in a
      large-scale clinical trial.
AB  - BACKGROUND: Patients in clinical trials of fibrinolytic agents have been shown to
      be younger, less often female, and to have lower risk characteristics and a
      better outcome compared with unselected patients with ST-elevation myocardial
      infarction. However, a direct comparison of patients treated with fibrinolytic
      agents and not enrolled versus those enrolled in a trial, including a large
      number of patients, has not been performed. METHODS: Prospective data from the
      Swedish Register of Cardiac Intensive Care on patients admitted with acute
      myocardial infarction treated with thrombolytic agents in 60 Swedish hospitals
      were linked to data on trial participants in the ASsessment of Safety and
      Efficacy of a New Thrombolytic (ASSENT)-2 trial of fibrinolytic agents. Baseline
      characteristics, treatments, and long-term outcome were evaluated in 729 trial
      participants (A2), 2048 nonparticipants at trial hospitals (non-A2), and 964
      nonparticipants at other hospitals (non-A2-Hosp). RESULTS: Nontrial patients
      compared with A2 patients were older and had higher risk characteristics and more
      early complications, although the treatments were similar. Patients at highest
      risk of death were the least likely to be enrolled in the trial. The 1-year
      mortality rate was 8.8% versus 20.3% and 19.0% (P <.001 for both) among A2
      compared with non-A2 and non-A2-Hosp patients, respectively. After adjustment for
      a number of risk factors, the 1-year mortality rate was still twice as high in
      nontrial compared with A2 patients. CONCLUSIONS: The adjusted 1-year mortality
      rate was twice as high in patients treated with fibrinolytic agents and not
      enrolled in a clinical trial compared with those enrolled. One major reason for
      the difference in outcome appeared to be the selection of less critically ill
      patients to the trial.

PMID- 15459585
TI  - Diagnostic value of serial measurement of cardiac markers in patients with chest
      pain: limited value of adding myoglobin to troponin I for exclusion of myocardial
      infarction.
AB  - BACKGROUND: Despite improved laboratory assays for cardiac markers and a revised
      standard for definition of myocardial infarction (AMI), early detection of
      coronary ischemia in unselected patients with chest pain remains a difficult
      challenge. METHODS: Rapid measurements of troponin I (TnI), creatine kinase MB
      (CK-MB), and myoglobin were performed in 197 consecutive patients with chest pain
      and a nondiagnostic electrocardiogram for AMI. The early diagnostic performances
      of these markers and different multimarker strategies were evaluated and
      compared. Diagnosis of AMI was based on European Society of Cardiology/American
      College of Cardiology criteria. RESULTS: At a given specificity of 95%, TnI
      yielded the highest sensitivity of all markers at all time points. A TnI cutoff
      corresponding to the 10% coefficient of variation (0.1 microg/L) demonstrated a
      cumulative sensitivity of 93% with a corresponding specificity of 81% at 2 hours.
      The sensitivity was considerably higher compared to CK-MB and myoglobin, even
      considering patients with a short delay until admission. Using the 99th
      percentile of TnI results as a cutoff (0.07 microg/L) produced a cumulative
      sensitivity of 98% at 2 hours, but its usefulness was limited due to low
      specificities. Multimarker strategies including TnI and/or myoglobin did not
      provide a superior overall diagnostic performance compared to TnI using the 0.1
      microg/L cutoff. CONCLUSION: A TnI cutoff corresponding to the 10% coefficient of
      variation was most appropriate for early diagnosis of AMI. A lower TnI cutoff may
      be useful for very early exclusion of AMI. CK-MB and in particular myoglobin did
      not offer additional diagnostic value.

PMID- 15459586
TI  - Retrospective evaluation of a pharmacokinetic program for adjusting enoxaparin in
      renal impairment.
AB  - BACKGROUND: Although clinical trials have found that enoxaparin clearance is
      prolonged in renal impairment, only one letter describes experience with
      adjusting doses. Only pharmacokinetic studies exist to guide dose adjustment in
      response to anti-Xa levels. Unfractionated heparin has comparable major bleeding
      in renal impairment compared with unadjusted enoxaparin. This necessitates a
      pharmacokinetic program to adjust enoxaparin with anti-Xa monitoring. METHODS: A
      pharmacokinetic program was created in response to adverse events and physician
      interest in a service. A program was designed providing all patients a loading
      dose of 1 mg/kg enoxaparin. Subsequent doses were 0.50 mg/kg per dose
      subcutaneously (SC) every 12 hours (q12h) for patients with a creatinine
      clearance (CrCl) < or =30 mL/min (severe group) and 0.75 mg/kg per dose SC q12h
      for patients with CrCl of 30 to 60 mL/min (moderate group). A 1-year review of
      170 hospitalized patients is reported. RESULTS: The mean +/- SD [95% CI] anti-Xa
      level 4 hours after the third dose was 0.65 +/- 0.19 [0.59 to 0.70] IU/mL for the
      severe group and 0.82 +/- 0.18 [0.79 to 0.85] IU/mL for the moderate group (P
      <.001). Eighty percent of patients with moderate renal failure and 60% of the
      patients with severe renal failure were in the therapeutic anti-Xa range after
      the third dose. A dose-adjustment ratio was used to adjust doses in patients
      whose levels were outside the therapeutic range: New dose = [(Current dose) x
      (Goal anti-Xa level)]/(Current anti-Xa level). An incidence of bleeding
      comparable to that found in normal patients was found. CONCLUSIONS: In high-risk
      patients, it is reasonable to limit the exposure of patients to low molecular
      weight heparins by using anti-Xa levels as a marker. The enoxaparin protocol for
      renally impaired patients successfully placed patients in the therapeutic range
      established by consensus guidelines. The dose-adjustment ratio adds significant
      understanding to the pharmacokinetics of dose adjustment.

PMID- 15459587
TI  - Are high doses of intracoronary adenosine an alternative to standard intravenous
      adenosine for the assessment of fractional flow reserve?
AB  - BACKGROUND: Achievement of maximal hyperemia of the coronary microcirculation is
      a prerequisite for the measurement of fractional flow reserve (FFR). Intravenous
      adenosine is considered the standard method, but its use in the catheterization
      laboratory is time consuming and expensive compared with intracoronary adenosine.
      Therefore, this study compared different high, intracoronary doses of adenosine
      for the potential to achieve a maximal hyperemia equivalent to the standard
      intravenous route. METHODS: FFR was assessed in 50 patients with 50 intermediate
      lesions during cardiac catheterization. FFR was calculated as the ratio of the
      distal coronary pressure to the aortic pressure at hyperemia. Different
      incremental doses of intracoronary adenosine (60, 90, 120, and 150 microg as
      boli) and a standard intravenous infusion of 140 microg/kg/min were administered
      in a randomized fashion. RESULTS: Different incremental doses of intracoronary
      adenosine were well tolerated, with fewer systemic adverse effects than
      intravenous adenosine. At baseline, there were no significant differences for
      mean aortic and distal coronary pressure or heart rate in the different adenosine
      doses and routes. FFR decreased with increasing adenosine doses, with the lowest
      values observed with the 150-microg intracoronary bolus and 140-microg/kg/min
      dose of intravenous adenosine. All intracoronary doses, except the 150-microg
      bolus, resulted in mean FFR values that were significantly (P <.05) higher than
      FFR after the administration intravenous adenosine. Furthermore, 5 patients (10%)
      with a FFR value >0.75 and 3 subjects (6%) with a FFR value >0.80 who received a
      60-microg intracoronary bolus reached a value below the cutoff point of 0.75 with
      the intravenous administration. CONCLUSIONS: This study suggests a dose-response
      relationship on hyperemia for intracoronary adenosine doses >60 microg. The
      administration of very high intracoronary adenosine boli is safe and associated
      with fewer systemic adverse effects than standard intravenous adenosine. However,
      intravenous adenosine administration with 140 microg/kg/min produced a more
      pronounced hyperemia than intracoronary adenosine in most patients and should be
      the preferred mode of application for the assessment of FFR.

PMID- 15459588
TI  - Evaluation of a scoring scheme, including proinsulin and the apolipoprotein
      B/apolipoprotein A1 ratio, for the risk of acute coronary events in middle-aged
      men: Uppsala Longitudinal Study of Adult Men (ULSAM).
AB  - BACKGROUND: In recent years, the importance of circulating levels of proinsulin
      and apolipoproteins as risk factors for myocardial infarction (MI) has been
      highlighted. The aims of the current study were to investigate whether
      introduction of these new markers of coronary risk could improve the performance
      of a risk prediction score and to compare this new score with traditional scoring
      schemes, such as the Framingham Study and the Prospective Cardiovascular Munster
      (PROCAM) Study schemes. METHODS: From 1970 to 1973 all 50-year-old men in
      Uppsala, Sweden, were invited to participate in a health survey aimed at
      identifying risk factors for cardiovascular disease (the Uppsala Longitudinal
      Study of Adult Men [ULSAM] cohort). The current study investigated metabolic
      characteristics at baseline and the incidence of fatal and nonfatal MI (n = 251)
      during 28.7 years of follow-up in 1108 men who were free of coronary heart
      disease at baseline. RESULTS: The risk prediction score was derived from one half
      of the population sample from the ULSAM cohort and included systolic blood
      pressure, smoking, family history of MI, serum proinsulin, and the ratio between
      apolipoprotein B and apolipoprotein A1. The score was highly predictive for
      future MI (hazard ratio, 1.77 for a 1 SD increase; 95% CI, 1.49 to 2.10, P
      <.0001) in the other half of the population that was not used for generating the
      score. The ULSAM score performed slightly better than the Framingham and PROCAM
      scores (evaluated as areas under the receiver operating curves; Framingham, 61%;
      PROCAM, 63%; ULSAM, 66%; P =.08). CONCLUSIONS: A risk prediction score for MI
      including proinsulin and the ratio between apolipoprotein B and apolipoprotein A1
      was developed in middle-aged men. This score was highly predictive for future
      fatal and nonfatal MI and proved to be at least as good as the Framingham and the
      PROCAM scores, being based on traditional risk factors.

PMID- 15459589
TI  - Short alleles of P-selectin glycoprotein ligand-1 protect against premature
      myocardial infarction.
AB  - BACKGROUND: Atherosclerosis is an inflammatory disease resulting from an injury
      that leads to an increase in the adhesiveness and permeability of the endothelium
      to leukocytes or platelets. The selectin family plays a key role initiating the
      cascade of events. Recently, we have demonstrated the functional relevance of a
      variable number of tandem repeats polymorphism affecting the P-selectin
      glycoprotein ligand (PSGL-1). Neutrophils carrying short alleles exhibit a
      significantly lower capacity to bind activated platelets. These alleles
      consistently protect against transient ischemic attack. We sought to evaluate the
      role of this polymorphism in premature myocardial infarction because genetic risk
      factors have more relevance in the development of disease in young patients.
      METHODS: We genotyped 219 Caucasian patients who had suffered a premature
      myocardial infarction (MI) (aged < or =45 years) and 594 control subjects from
      our Mediterranean area. The role of the PSGL-1 polymorphism was also evaluated
      according to the additional risk factors of age, sex, smoking history,
      hypertension, hypercholesterolemia, and diabetes. RESULTS: The frequency of the
      short alleles (B and C) was significantly lower in patients than in controls (P
      =.012, odds ratio 0.62; 95% CI 0.42-0.92). Multiple regression analysis revealed
      that B and C alleles had an independent protective effect on the development of
      premature MI (P =.034, odds ratio 0.62 95%CI: 0.40-0.96). CONCLUSIONS: We found
      an interesting association between a functional polymorphism and the risk of MI
      at a younger age. According to our results, the short B and C PSGL-1 alleles
      might protect against premature MI, probably because of their lesser adhesive
      capacity.

PMID- 15459590
TI  - Racial differences in endothelial function in postmenopausal women.
AB  - OBJECTIVE: Racial differences in cardiovascular mortality among women remain
      largely unexplained. Preliminary data suggest that African American and Caucasian
      differences in endothelial function may parallel differential cardiovascular
      disease (CVD) risk in women. To further study differences in endothelial function
      between African American and Caucasian women, we analyzed measures of brachial
      artery flow-mediated dilation (FMD) in women enrolled in the Cardiovascular
      Health Study (CHS). METHODS AND RESULTS: Brachial artery FMD was measured in the
      fasting state using established ultrasound techniques in 1330 Caucasian and 297
      African American female participants in CHS (mean age 78.4 +/- 4.4 years).
      General linear models were used to compare FMD between African American and
      Caucasian women after adjusting for baseline brachial diameter, hypertension,
      diabetes, smoking, cholesterol, systolic blood pressure, body mass index,
      waist/hip ratio, age, education, income level; use of angiotensin-converting
      enzyme inhibitors, beta-blockers, nitroglycerin, estrogens and lipid-lowering
      drugs; and presence of clinical or subclinical disease. Adjusted absolute change
      and percent change in brachial artery diameter was significantly reduced in
      African American women compared with Caucasian women (P <.0001 and P =.0002,
      respectively). Similar results were found when the women were stratified by
      history of CVD (- CVD, P =.02; + CVD, P =.001) and CVD or subclinical vascular
      disease (- disease, P =.01, + disease, P =.03). CONCLUSIONS: In this cohort,
      brachial artery FMD was lower in African American women compared to Caucasian
      women, and this difference persisted after adjustment by multivariable analysis.
      The increased CVD risk in African American women may be related to impaired
      endothelial function. It remains to be determined whether African American women
      may uniquely benefit by interventions designed to improve endothelial health.

PMID- 15459591
TI  - N-terminal B-type natriuretic peptide predicts extent of coronary artery disease
      and ischemia in patients with stable angina pectoris.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) and its N-terminal fragment (NT
      proBNP) are elevated in patients with acute coronary syndromes and are closely
      linked to prognosis. Because there is only a small amount of data available
      concerning NT-proBNP in patients with stable angina pectoris, we aimed to
      determine whether NT-proBNP is of additional diagnostic value in these patients.
      METHODS AND RESULTS: Ninety-four patients with stable angina pectoris were
      prospectively included. All patients underwent exercise testing and coronary
      angiography, and 91 patients received thallium-201 single-photon emission
      computed tomography myocardial scintigraphy. NT-proBNP was analyzed at rest and
      after exercise testing. NT-proBNP was elevated in patients with inducible
      myocardial ischemia shown by single-photon emission computed tomography (396 +/-
      80 pg/mL vs 160 +/- 101 pg/mL; P <.01) closely linked to the extent of coronary
      artery disease (CAD) (no CAD, 148 +/- 29 pg/mL; 1- or 2-vessel disease, 269 +/-
      50 pg/mL; 3-vessel disease 624 +/- 186 pg/mL; P <.01). In a multivariate
      analysis, NT-proBNP was an independent predictor for CAD. The area under the
      curve of the receiver operating characteristic curve was 0.72 for NT-proBNP to
      predict CAD. Using an optimized cut off level of 214 pg/mL, CAD can be predicted
      with high accuracy. The total test efficiency of exercise testing can be improved
      from 1.46 to 1.52 when combined with NT-proBNP measurement. CONCLUSION: NT-proBNP
      is elevated in patients with stable angina pectoris and has a close correlation
      to disease severity. Combining the measurement of NT-proBNP with exercise
      testing, the test accuracy for predicting severe CAD can be improved. Our data
      show an incremental value of NT-proBNP in the diagnostic process of stable angina
      pectoris.

PMID- 15459592
TI  - Are exercise stress tests appropriate for assessing myocardial ischemia in
      patients with major depressive disorder?
AB  - BACKGROUND: Major depressive disorder (MDD) disproportionately affects patients
      with coronary artery disease (CAD). Evidence of myocardial ischemia with
      electrocardiography (ECG) or single-photon-emission-computed-tomography (SPECT)
      assessments during exercise testing is an important determinant of CAD prognosis.
      However, many key symptoms of MDD, such as reduced interest in daily activities,
      lack of energy, and fatigue, may affect exercise performance and the detection of
      ischemia in patients with MDD. This study evaluated the extent to which MDD and
      depressive symptomatology moderate exercise test performance and compared the
      ability of ECG versus SPECT for detecting ischemia in 1367 consecutive patients
      who underwent exercise testing. METHODS: All patients underwent a brief,
      structured psychiatric interview (PRIME-MD) and completed the Beck Depression
      Inventory (BDI) on the day of their exercise (treadmill) test. RESULTS: A total
      of 183 patients (13%) met diagnostic criteria for MDD. Patients with MDD achieved
      a significantly lower percent of maximal predicted heart rate (%MPHR), exhibited
      lower peak exercise mets, and spent less time exercising compared with patients
      without MDD (all P values <.05). BDI scores were also negatively correlated with
      all 3 indices of exercise performance (all P values <.01). There were no
      differences in rates of SPECT ischemia in patients with MDD (40%) versus patients
      without MDD (45%; P =.23); however, rates of ECG ischemia were significantly
      lower (30%) in patients with MDD than in patients without MDD (48%; P <.0001).
      CONCLUSIONS: Results suggest that patients with CAD who have MDD, depressive
      symptomatology, or both exhibit poor exercise tolerance and performance and that
      ECG, as compared with SPECT, may not be as reliable in detecting ischemia in
      patients who are depressed.

PMID- 15459593
TI  - Effects of graded-release diltiazem versus ramipril, dosed at bedtime, on early
      morning blood pressure, heart rate, and the rate-pressure product.
AB  - BACKGROUND: Therapeutic agents for the treatment of hypertension may differ in
      their efficacy during the early morning period, a time when both morbid and
      mortal cardiovascular events are increased compared to other times of the day.
      METHODS: We studied the effects of a graded-release delivery system of diltiazem
      (diltiazem HCL extended release tablets) versus ramipril, both dosed at bedtime,
      on blood pressure (BP), heart rate, and the heart rate-systolic BP product during
      the first 4 hours after awakening in a double-blind, titration-to-effect trial.
      There were 261 men and women enrolled in the trial with an untreated sitting
      diastolic BP of 90 to 109 mm Hg and ambulatory daytime diastolic BP of 85 to 109
      mm Hg. Patients were randomized to either diltiazem extended release (ER) tablets
      each evening (240 mg titrated to 360 mg and to 540 mg) or ramipril each evening
      (5 mg titrated to 10 mg and to 20 mg). Early morning assessments of BP, heart
      rate, and the heart rate-systolic BP product were performed using 24-hour
      ambulatory recordings after 10 weeks of therapy. RESULTS: In each therapeutic
      group, 76% of patients were titrated to the highest possible dose. After 10 weeks
      of treatment, reductions in early morning BP by diltiazem ER tablets were
      significantly greater (-18/-15 mm Hg) than reductions by ramipril (-13/-8 mmHg, P
      <.005 for systolic BP and P <.001 for diastolic BP). Diltiazem ER tablets also
      led to greater reductions in morning heart rate and the heart rate-pressure
      product compared to ramipril. Reductions in mean 24-hour diastolic BP, heart
      rate, and the rate-pressure product were greater in patients treated with
      diltiazem ER tablets compared to ramipril, while reductions in 24-hour systolic
      BP were similar in each group. The observed adverse effects were not serious and
      incidences were similar for the 2 treatment groups. CONCLUSIONS: These data
      demonstrate that bedtime administration of diltiazem ER, an agent designed to
      parallel the circadian rhythm of BP and heart rate, led to significantly greater
      early morning hemodynamic effects compared to the angiotensin-converting enzyme
      inhibitor ramipril, also dosed in the evening.

PMID- 15459594
TI  - Effects of statin treatment on uric acid homeostasis in patients with primary
      hyperlipidemia.
AB  - BACKGROUND: Epidemiologic studies have shown that serum uric acid is a risk
      factor of coronary artery disease. In addition to fenofibrate, there is some
      evidence that atorvastatin may have a hypouricemic action, but the underlying
      mechanisms remain speculative. METHODS: This randomized trial was conducted to
      investigate the effects of atorvastatin and simvastatin on uric acid homeostasis
      in patients treated for primary hyperlipidemia. A total of 180 patients were
      enrolled; patients were randomly assigned to 40 mg/d of either atorvastatin or
      simvastatin. Serum lipid and metabolic parameters were measured at baseline and
      at 6 and 12 weeks of treatment; random urine samples were simultaneously obtained
      for creatinine, sodium, and uric acid determinations. RESULTS: Baseline serum
      uric acid levels correlated positively with the body mass index, serum insulin,
      creatinine, and triglyceride levels and inversely with serum HDL cholesterol
      levels. Both statins caused a favorable effect on lipids and a significant
      decrease in fibrinogen and high-sensitivity CRP levels. However, only
      atorvastatin reduced serum uric acid levels (from 5.6 +/- 1.7 to 4.9 +/- 1.5
      mg/dL, P <.0001) by augmenting its urinary fractional excretion (from 10.4% +/-
      7.9% to 12.0% +/- 7.4%, P <.01). In a multivariate logistic regression analysis,
      the reduction of uric acid levels was independently associated with baseline
      serum uric acid concentration but not to other variables, including lipid
      parameters (OR, 1.65; 95% CI, 1.14 to 2.40; P =.008). CONCLUSIONS: Atorvastatin
      (but not simvastatin) significantly lowered serum uric acid levels. This result
      may be in favor of a preferable choice of atorvastatin for the treatment of
      hyperlipidemic patients presenting with hyperuricemia.

PMID- 15459595
TI  - Amiodarone versus sotalol for the treatment of atrial fibrillation after open
      heart surgery: the Reduction in Postoperative Cardiovascular Arrhythmic Events
      (REDUCE) trial.
AB  - OBJECTIVES: This prospective, randomized, double-blind, placebo-controlled study
      compared the efficacy and safety of amiodarone and sotalol in the prevention of
      atrial fibrillation (AF) following open heart surgery. BACKGROUND: The incidence
      of supraventricular arrhythmias following open heart surgery ranges from 20% to
      40%, with AF being the most common. Both amiodarone and sotalol have been shown
      to be effective in reducing postoperative arrhythmias, but no direct comparison
      of these agents has been conducted. METHODS: A total of 160 patients were
      randomized, of whom 134 underwent coronary artery bypass graft surgery (CABG)
      alone, 17 underwent CABG and concomitant aortic valve replacement surgery (AVR),
      9 underwent AVR only, and 1 patient's surgery was canceled. Patients with signs
      or symptoms of congestive heart failure (CHF), ejection fraction < or =30%,
      estimated creatinine clearance <30 mL/min, or serum creatinine > or =2.5 mg/dL
      were excluded. Patients were randomized to receive either sotalol 80 mg 2 times
      per day (n = 76) or intravenous amiodarone 15 mg/kg over 24 hours followed by
      oral amiodarone 200 mg 3 times per day (n = 83). Study drug was started at the
      time of surgery and continued for 7 days or until discharge, whichever came
      first. RESULTS: AF occurred in 17% of patients randomized to amiodarone and 25%
      of the patients randomized to sotalol (P =.21). However, the duration of AF was
      significantly shorter in amiodarone-treated patients (169 +/- 224 min) compared
      to sotalol treated patients (487 +/- 505 min; P =.04). In a subgroup analysis,
      the incidence of AF in patients undergoing AVR or CABG with AVR was significantly
      less with amiodarone (1/15, 7%) compared to sotalol (9/11, 82%) (P <.001). Blood
      pressure was lower immediately after surgery with amiodarone but comparable to
      sotalol at 24 hours. Of the hemodynamic indices measured, only stroke volume was
      significantly lower in patients randomized to sotalol at 24 hours (P =.035).
      CONCLUSIONS: Amiodarone and sotalol share similar efficacy and safety in reducing
      postoperative AF. Hemodynamic effects were similar between both drugs at 24
      hours, with the exception that stroke volume was lower in sotalol-treated
      patients. In patients undergoing more complex surgery, postoperative AF occurred
      more frequently with sotalol than with amiodarone.

PMID- 15459596
TI  - The association of left atrial size and occurrence of atrial fibrillation: a
      prospective cohort study from the Canadian Registry of Atrial Fibrillation.
AB  - BACKGROUND: The effect of left atrial (LA) dimension on the recurrence of atrial
      fibrillation (AF) has been examined in small studies. We evaluated the effect of
      LA dimension on the occurrence of AF using 2- and 4-year echocardiographic data
      in a large cohort of patients with new onset AF. METHODS: The Canadian Registry
      of AF (CARAF) enrolled subjects with AF at the first electrocardiographically
      confirmed diagnosis. Patients were classified at 2 and 4 years as no recurrent AF
      (No RAF), paroxysmal AF (PAF), or chronic AF (CAF) based on clinical symptoms and
      electrocardiographic documentation. The association between baseline, 2-, and 4
      year LA dimensions with occurrence of AF as determined by echocardiography was
      evaluated using a multivariate analysis. RESULTS: The No RAF group (n = 176) had
      a significantly smaller LA dimension (36.9 +/- 6.8 mm) at baseline compared to
      the CAF group (n = 227) (42.8 +/- 7.5 mm, P <.0001). The No RAF and PAF (n = 153)
      groups did not have a significant change in LA dimension at 2 or 4 years. Only
      those with CAF had a significant increase in LA dimension at 2 and 4 years, +1.39
      mm (95% CI 0.01-2.8) and +3.48 mm (95% CI 1.8-5.2), respectively. CONCLUSIONS: A
      larger baseline LA dimension is associated with progression to CAF. Patients with
      no or paroxysmal recurrence had no change in LA dimension over a 4-year period.
      These findings have implications in tailoring modes of therapy in patients with
      AF.

PMID- 15459597
TI  - Serum B-type natriuretic peptide levels on admission predict not only short-term
      death but also angiographic success of procedure in patients with acute ST
      elevation myocardial infarction treated with primary angioplasty.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) levels are predictive of short-term
      death in patients with acute coronary syndromes. Few data are available for BNP
      levels obtained on admission in patients with acute ST-elevation myocardial
      infarction (STEMI) treated with primary percutaneous coronary intervention (PCI).
      METHODS: Blood samples for BNP estimation, obtained on admission in 126
      consecutive patients (mean age, 58.8 +/- 10.7 years) with STEMI, were measured at
      the bedside by using a simple point-of-care test in a 15-minute period before
      PCI. Follow-up up to 42 days was performed. RESULTS: A baseline BNP value of 331
      pg/mL had a sensitivity of 87.9% and a specificity of 90% for predicting death in
      a follow-up study. There was no difference in subgroups by median BNP (100 pg/mL)
      in Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 before PCI, although
      higher BNP levels were observed among patients with TIMI <3 after PCI than among
      those with TIMI 3 (356.7 +/- 350.8 vs 144.9 +/- 191.2 pg/mL; P <.0001). In
      multivariate logistic regression analysis, admission BNP was the independent
      predictor for the following: death (odds ratio [OR], 16.3; 95% confidence
      interval [CI], 1.4 to 186.7; P =.03), TIMI grade <3 after PCI (OR, 3.4; 95% CI,
      1.2 to 9.6; P =.02), and the no-reflow phenomenon (OR, 6.2; 95% CI, 1.7 to 23; P
      =.007) after adjusting for other variables. CONCLUSIONS: BNP levels obtained on
      admission are a powerful, independent predictor of short-term death and
      angiographic success after PCI in patients with STEMI. The no-reflow phenomenon
      may be predicted in STEMI on the basis of high serum BNP values on admission.

PMID- 15459599
TI  - Cytomegalovirus and Chlamydia pneumoniae as predictors for adverse events and
      angina pectoris after percutaneous coronary intervention.
AB  - BACKGROUND: The aim of our study was to investigate the influence of prior
      cytomegalovirus (CMV) or Chlamydia pneumoniae (CP) infection on prognosis after
      percutaneous coronary intervention (PCI). METHODS: Using the enzyme-linked
      immunosorbent assay technique preprocedural anti-CMV immunoglobulin G and anti-CP
      immunoglobulin A (CP IgA), immunoglobulin M, and immunoglobulin G antibodies were
      measured. Repeat anginal complaints and major adverse clinical events (MACE),
      including PCI, coronary artery bypass grafting, myocardial infarction, and death,
      were recorded at 8-month follow-up. RESULTS: Six hundred consecutive patients
      were included after successful PCI. Sixty-four percent of the patients were
      stented. The mean age was 61.6 years, and 68.9% were male. The rate of
      seropositivity for CP IgA in patients with MACE as compared with patients without
      MACE was 50.9% versus 35.4% (P =.0276). In patients with repeat anginal
      complaints, CP IgA seropositivity was 41.6% versus 34.6% in patients without
      repeat angina (P =.1057). The negative effect of CP on prognosis was confirmed
      after calculating the odds ratios for MACE (1.9, 95% CI 1.1-3.3). The rates of
      seropositivity for anti-CMV immunoglobulin G were not significantly different
      between both groups, although we found an association between infectious burden
      and repeat angina pectoris (odds ratio 1.8, 95% CI 1.1-3.0). CONCLUSIONS: We
      conclude that preprocedural seropositivity of CP IgA is a risk factor for MACE
      and angina pectoris after PCI. Although no such relation was found for CMV alone,
      the cumulative infectious burden was also related to these clinical
      manifestations of restenosis.

PMID- 15459598
TI  - Randomized comparison of debulking followed by stenting versus stenting alone for
      ostial left anterior descending artery stenosis: intravascular ultrasound
      guidance.
AB  - BACKGROUND: Although directional coronary atherectomy (DCA) before stenting has
      the advantage of combining substantial removal of atheromatous plaque and
      prevention of elastic recoil, there has been no randomized study to investigate
      its efficacy in ostial left anterior descending artery (LAD) lesions. This study
      was aimed to evaluate the effect of DCA followed by stenting on ostial LAD
      stenosis under the guidance of intravascular ultrasound (IVUS). METHODS: Eighty
      six patients with ostial LAD stenoses were randomly assigned to DCA followed by
      stenting (group I) or stenting alone (group II). Aggressive DCA or optimal
      stenting was performed in both groups under the guidance of IVUS. The primary end
      point was angiographic restenosis at 6 months. RESULTS: Baseline clinical and
      angiographic characteristics were similar between the 2 groups. The
      postprocedural minimal lumen diameter was larger in group I than group II (4.0 +/
      0.4 mm vs. 3.5 +/- 0.5 mm, P <.001). However, the angiographic restenosis rates
      were not significantly different between the 2 groups (9/32 [28.1%] in group I
      vs. 11/30 [36.7%] in group II, P =.472). The postprocedural IVUS stent area was
      the only independent determinant of restenosis by multivariate analysis (odds
      ratio.61, 95% CI 0.41-0.92, P =.018). CONCLUSIONS: DCA followed by stenting
      achieved greater lumen gain than stenting alone for ostial LAD stenosis. However,
      DCA did not improve angiographic restenosis.

PMID- 15459600
TI  - Safety of elective--including "high risk"--percutaneous coronary interventions
      without on-site cardiac surgery.
AB  - BACKGROUND: Current guidelines (American College of Cardiology/American Heart
      Association) for percutaneous coronary intervention (PCI) limit the performance
      of elective cases to hospitals with the capability for cardiac surgery. The
      number of hospitals in the United States with this capability is limited, which
      restricts availability of this proven technology. OBJECTIVE: To determine the
      safety of performing elective, nonselected PCI in hospitals without cardiac
      surgery capability. DESIGN, SETTING, AND PATIENTS: A single-center retrospective
      analysis of the first 1000 patients undergoing elective, including "high-risk,"
      PCI in the county hospital in Phoenix, Arizona. MAIN OUTCOME MEASURES: A database
      (Access Microsoft Windows) was established to follow patient characteristics,
      indications for the procedure, technical aspects of the procedure, outcomes and
      complications. The Quality Improvement Committee followed each case closely to
      independently assess the adequacy of indications and patient management, with a
      monthly case review of every patient who had a periprocedural or postprocedural
      complication. RESULTS: Failure to complete target vessel revascularization
      occurred in 68 of the total 1756 vessels (3.8%). Seven patients (0.7%), required
      elective referral for coronary artery bypass graft surgery after failed PCI.
      Coronary perforations occurred in 9 patients (0.9%); all resolved with
      percutaneous techniques. Postprocedure myocardial infarction was diagnosed in 21
      patients (2.1%). Two patients (0.2%) developed a stroke. Periprocedural death
      (within 48 hours of the procedure) occurred in 2 patients (0.2%). Out of the 1000
      interventions performed, none required emergency coronary artery bypass graft
      surgery. CONCLUSIONS: Technical advances in interventional cardiology allow for
      safe performance of PCI in hospitals without on-site cardiac surgery facilities
      if proposed conditions are met. Our results together with the vast experience in
      other countries supports a paradigm change that would increase the number of
      hospitals that can offer interventional cardiology procedures with a
      corresponding increase in the number of patients that would benefit.

PMID- 15459601
TI  - Peripheral vascular endothelial function testing for the diagnosis of coronary
      artery disease.
AB  - BACKGROUND: Abnormalities in endothelium-dependent vasodilation may be detected
      in arteries before the development of overt atherosclerosis, and their presence
      may predict stress-induced ischemia as assessed by ST-segment depression and/or
      perfusion defects. Brachial artery ultrasound during reactive hyperemia is a
      noninvasive method of assessing peripheral vasomotion, measured by flow-mediated
      vasodilation (FMD). The purpose of the current study was to assess whether
      endothelium-dependent FMD of the brachial artery, by ultrasound imaging, predicts
      the presence of angiographically assessed coronary artery disease (CAD). METHODS:
      One hundred ninety-eight in-hospital patients (age, 59 +/- 9 years; 78 women)
      with chest pain syndrome and without previous myocardial infarction or
      revascularization procedures were enrolled in the present study. All of the
      patients, at testing time, were not receiving nitrate therapy and underwent, on
      different days, coronary angiography and endothelium-dependent FMD testing of the
      brachial artery by high-resolution ultrasound. The result of the flow-mediated
      dilation (%FMD) is defined as the percent change in the internal diameter of the
      brachial artery during reactive hyperemia related to baseline. A coronary vessel
      was considered to have a significant obstruction if its diameter was narrowed by
      50% or more on quantitative computer-assisted analysis. A prognostically
      validated angiographic Duke score (from 0 = normal to 100 = severe left main
      disease) was calculated. RESULTS: The %FMD was lower in patients with (n = 69)
      compared with those without (n = 129) CAD (4.64% +/- 4.36% vs 7.39% +/- 5.68%; P
      =.01). By multivariate analysis, the %FMD (P =.01; odds ratio [OR], 1.13; 95%
      confidence interval [CI], 1.05 to 1.23), male sex (P =.01; OR, 3.47; 95% CI, 1.64
      to 7.36), and cigarette smoking habit (P <.01; OR, 4.00; 95% CI, 2.50 to 6.35)
      were independent predictors of CAD. %FMD was poorly albeit significantly
      correlated with the severity of CAD (%FMD Duke score, P <.01, r = -0.25). The
      receiver operator characteristic curve showed the %FMD optimal cutoff value as <
      or =8.84, with sensitivity of 90%, specificity of 37%, negative predictive value
      of 90%, and positive predictive value of 43%. CONCLUSIONS: In patients with chest
      pain, a depressed FMD of the brachial artery was a sensitive indicator of CAD,
      but it showed poor specificity, and it appeared to be unable to predict both the
      extent and the severity of angiographically assessed CAD.

PMID- 15459602
TI  - N-acetylcysteine reduces contrast-associated nephropathy but not clinical events
      during long-term follow-up.
AB  - BACKGROUND: Contrast-associated nephropathy (CAN) is associated with increased
      morbidity and mortality following percutaneous coronary intervention (PCI). N
      acetylcysteine (NAC) has been shown to reduce the risk of nephropathy; however,
      the impact of NAC on long-term clinical outcomes has not been assessed. METHODS:
      This randomized, double-blind, placebo-controlled trial enrolled 180 patients
      with moderate renal dysfunction undergoing PCI or coronary angiography with a
      high likelihood of ad hoc PCI; 171 patients completed the clinical follow-up.
      Patients received oral NAC (2000 mg/dose, n = 95) or placebo (n = 85) twice a day
      for 3 doses if randomized the night prior to the procedure, and 2 doses if
      randomized the day of the procedure. The primary end point was the incidence of a
      > or =25% increase in serum creatinine level 48 to 72 hours after PCI. Secondary
      end points were the inhospital incidence of death, nonfatal myocardial
      infarction, or urgent dialysis, and the 9-month incidence of death, nonfatal
      myocardial infarction, need for dialysis, or repeat hospitalization for cardiac
      reasons. RESULTS: CAN occurred in 9.6% of patients assigned to NAC and 22.2% of
      patients assigned to placebo (P =.04); 1 patient receiving NAC required urgent
      dialysis. The inhospital composite end point occurred in 7 (7.4%) NAC-treated and
      3 (3.5%) placebo-treated patients, P = NS. At 9 months, the composite end point
      occurred in 23 (24.2%) NAC-treated patients and 18 (21.2%) placebo-treated, P =
      NS. CONCLUSION: Although high-dose NAC prevented periprocedural CAN, this benefit
      did not translate into a decrease in adverse outcomes over 9 months. Further
      studies to determine the clinical utility of this drug are required.

PMID- 15459603
TI  - Tissue Doppler imaging in patients with moderate to severe aortic valve stenosis:
      clinical usefulness and diagnostic accuracy.
AB  - BACKGROUND: Mitral annular velocities derived from tissue Doppler imaging (TDI)
      provide information about left ventricular (LV) long-axis function and allow for
      the assessment of LV filling pressures in selected subsets of patients. It was
      the aim of this study to assess the usefulness of TDI in patients with moderate
      to severe aortic valve stenosis (AS). METHODS: Twenty-three patients with
      moderate to severe AS (mean aortic valve area 0.8 +/- 0.4 cm2), in whom coronary
      artery disease had been ruled out, and 36 asymptomatic age-matched control
      subjects underwent assessment of ejection fraction, fractional shortening, and
      mitral inflow (E, A, E/A ratio). TDI velocities (S', E', A') were derived from
      the septal mitral annulus. In patients with AS, LV pressure before atrial
      contraction (LV pre-A pressure), LV end-diastolic pressure, and cardiac index
      were measured during cardiac catheterization. RESULTS: In patients with AS,
      systolic (S') and early diastolic mitral annular velocities (E') were
      significantly reduced in comparison to control subjects (systolic, 5.5 +/- 1.2 vs
      8.3 +/- 1.3 cm/s; early diastolic, 5.6 +/- 1.6 vs 10.2 +/- 3.0 cm/s, P <.001 for
      both comparisons), but ejection fraction, fractional shortening, and cardiac
      index were normal. In patients with AS, LV pre-A pressures (14 +/- 4 mm Hg) and
      end-diastolic pressures were high (19 +/- 7 mm Hg). In such patients, the mitral
      E/E' ratio was significantly related to LV pre-A pressure (r = 0.75, P <.001) and
      to LV end-diastolic pressure (r = 0.78, P <.001). In patients with AS, an E/E'
      ratio > or =13 identified an LV end-diastolic pressure >15 mm Hg, with a
      sensitivity of 93% and a specificity of 88%. CONCLUSIONS: In patients with
      moderate to severe AS, TDI allows for a reliable, noninvasive estimation of
      filling pressures. In such patients, systolic long-axis function is impaired even
      in the presence of normal ejection fraction and cardiac index. Thus, TDI
      integrates information about systolic and diastolic performance and may be a
      useful addition in the echocardiographic workup and care of patients with AS.

PMID- 15459604
TI  - Does chronic mitral regurgitation influence Doppler pressure half-time-derived
      calculation of the mitral valve area in patients with mitral stenosis?
AB  - BACKGROUND: In patients with mitral stenosis (MS), Doppler pressure half-time
      (PHT) may be influenced by hemodynamic variables other than the anatomic mitral
      valve orifice narrowing. This study was undertaken to assess whether the presence
      of concomitant mitral regurgitation (MR) affects mitral valve area (MVA)
      estimation by PHT. METHODS: Consecutive patients (n = 166) with noncalcific MS,
      in sinus rhythm, were studied. Group 1 (n = 106) had no or mild MR, and group 2
      (n = 60) had moderate or severe MR. MVA was assessed by using the PHT method and
      planimetry. RESULTS: There was a strong correlation between planimetry and PHT
      MVA in both groups (group 1: r = 0.86, P <.001; group 2: r = 0.73, P <.001).
      However, compared with planimetry MVA, PHT underestimated MVA by > or =20% in 18
      patients (17%) in group 1 and 21 patients (35%) in group 2 (P <.01).
      Overestimation by > or =20% occurred in 12 patients (11%) in group 1 and in 7
      (12%) in group 2. Group 2 subanalysis (group 2A: moderate MR, n = 16; group 2B:
      severe MR, n = 44) revealed that linear regression weakened with increasing
      severity of MR (group 2A: r = 0.824, P <.001, group 2B: r = 0.70, P <.001). PHT
      underestimation of MVA occurred in 31% and 36% of patients in Groups IIA and IIB,
      respectively (P = NS). CONCLUSIONS: PHT appears to be reliable for estimating MVA
      in most patients with MS, even in the presence of MR. However, the presence of
      significant MR reduces the reliability of PHT-derived MVA, with underestimation
      of MVA in a significant number of subjects. The severity of MR has a direct
      impact on PHT-derived MVA.

PMID- 15459605
TI  - Time trends in the use of beta-blockers and other pharmacotherapies in older
      adults with congestive heart failure.
AB  - BACKGROUND: Evidence supporting pharmacotherapy of congestive heart failure (CHF)
      has grown substantially over the past decade and includes large, placebo
      controlled trials with mortality end points. We describe beta-blocker and other
      medication temporal treatment trends of CHF in the Cardiovascular Health Study, a
      community-based cohort study of 5888 adults > or =65 years of age. METHODS:
      Prescription medication data were collected from hospital discharge summaries for
      incident CHF events and at in-study annual clinic visits for prevalent CHF cases
      from 1989 to 2000. Change in use of agents over time was estimated by using
      generalized estimating equations while adjusting for potential confounding
      factors of age, sex, race, and cardiovascular and pulmonary comorbidities.
      RESULTS: Among 1033 incident CHF events, beta-blocker use after diagnosis
      increased an average of 2.4 percentage points annually (95% CI, 1.5 to 3.4
      points) from 1989 to 2000. The increasing trend was consistent throughout follow
      up. Among participants with coronary disease and/or hypertension and among those
      with low ejection fractions (<45%), beta-blocker use remained flat from 1989 to
      1994 and increased 4.7 points annually (2.5 to 6.9) and 10.0 points annually (6.1
      to 13.8), respectively, from 1995 to 2000. Among participants without coronary
      disease or hypertension, there was no overall increase in use. Use of renin
      angiotensin system inhibitors increased 2.3 points annually (1.0 to 3.5), digoxin
      use decreased 2.4 points annually (-3.6 to -1.1), and loop diuretic use remained
      flat between 1989 and 2000. In general, treatment trends were similar for
      prevalent CHF. CONCLUSIONS: Treatment of CHF has changed gradually in the 1990s
      and may in part reflect the influence of CHF clinical trial evidence.

PMID- 15459606
TI  - Beta-blocker therapy for heart failure outside the clinical trial setting:
      findings of a community-based registry.
AB  - BACKGROUND: beta-Blockers reduce morbidity and mortality rates in heart failure
      (HF) clinical trials, but it is unknown whether these findings persist in the
      community setting. METHODS: A registry was created to survey tolerability and
      outcomes during initiation and 1-year follow-up of beta-blocker treatment with
      carvedilol in patients with HF treated by cardiologists (CARD) and primary care
      physicians (PCP) in the community. RESULTS: A total 4280 patients were enrolled
      (3121 by 259 CARD, 1159 by 129 PCP). Patient age averaged 67 +/- 13 years; 35%
      were women and 12% were black. The left ventricular ejection fraction averaged 31
      +/- 12; New York Heart Association class was II-III in 86% and IV in 3%. Patients
      of PCP had higher left ventricular ejection fraction, were older, and more
      frequently were female, black, diabetic, hypertensive, and in New York Heart
      Association class III/IV. Minimal difficulty titrating carvedilol was noted by
      >80% of CARD and PCP. Significantly more CARD-treated patients reached carvedilol
      doses of 25 mg twice daily (49% vs 27%). Kaplan-Meier all-cause mortality rate
      was 8.5% at 1 year and did not differ between CARD-treated and PCP-treated
      patients (8.2% vs 9.3%, P =.254). At least one HF hospitalization occurred in 11%
      of patients during follow-up, compared with 28% in the preceding year.
      CONCLUSIONS: Community-based physicians use carvedilol with success approaching
      that of clinical trials. Overall mortality rates and HF hospitalizations were in
      the same low range as in clinical trials. Thus, it appears that results of
      clinical trials with carvedilol for HF can be translated to the community
      setting.

PMID- 15459607
TI  - Impact of preoperative intravenous nitroglycerin on in-hospital outcomes after
      coronary artery bypass grafting for unstable angina.
AB  - BACKGROUND: Intravenous nitroglycerin (NTG) is an effective therapy for unstable
      angina (UA), but it may induce endothelial dysfunction and impair vascular nitric
      oxide signaling. We sought to determine whether preoperative intravenous NTG
      administration alters in-hospital outcomes in patients undergoing coronary artery
      bypass grafting (CABG) for UA. METHODS AND RESULTS: All in-hospital patients with
      Canadian Cardiovascular Society class IV angina who had isolated CABG between
      March 1995 and July 2002 at two Canadian centers were identified (n = 3976). Of
      these, 2506 were not receiving intravenous NTG and 1470 were receiving
      intravenous NTG at the time of CABG. Outcomes assessed were in-hospital mortality
      (IHM), intraoperative or postoperative aortic balloon pump use, perioperative
      myocardial infarction, prolonged (> or =24 hours) ventilation (p-vent), and a
      composite outcome, defined as any one or more of the above. Unadjusted IHM (5.9%
      vs 4.2%, P =.02), p-vent (22.2% vs 10.5%, P =.0001), and composite outcome (26.5%
      vs 15.2%, P =.0001) were higher in patients receiving intravenous NTG. Logistic
      regression showed that preoperative intravenous NTG was not an independent
      predictor of composite outcome (OR, 1.1; P =.49) or IHM (OR, 0.94; P =.69).
      Propensity score analysis was used to match two subgroups of patients (group 1,
      intravenous NTG, n = 1176; group 2, no intravenous NTG, n = 1176) on multiple
      factors. After adjustment with the propensity score, preoperative intravenous NTG
      use had no significant effect on any of the outcomes assessed. CONCLUSIONS:
      Despite its potential to induce endothelial dysfunction and impair vascular
      nitric oxide signaling, preoperative intravenous NTG administration is not
      associated with altered in-hospital outcomes after CABG for UA.

PMID- 15459608
TI  - Evidence for association between endothelial nitric oxide synthase gene
      polymorphism (G894T) and inflammatory markers: the ATTICA study.
AB  - BACKGROUND: We evaluated the effect of the point mutation of guanine to thymine
      at nucleotide position 894 (G894T) of the endothelial nitric oxide synthase
      (eNOS) gene on inflammatory and oxidative stress markers. METHODS: We studied
      genetic information from 270 men (18-87 years old) and 325 women (18-89 years
      old). Participants without any clinical evidence of cardiovascular or other
      atherosclerotic disease were randomly selected from the general population
      according to the age-sex distribution of Athens greater area. Genomic DNA was
      extracted from 2 to 5 mL of fresh or frozen whole blood using standard methods.
      RESULTS: The DNA analysis showed that 10.6% of the participants were Asp
      homozygotes (Asp/Asp), 40% heterozygotes (Asp/Glu) and 49.4% Glu-homozygotes
      (Glu/Glu). Compared to Asp/Glu and Glu/Glu, Asp/Asp had higher levels of
      fibrinogen (332 +/- 46 or 329 +/- 33 vs 319 +/- 29 mg/dL, P =.029), white blood
      cells (6.9 +/- 0.6 or 6.5 +/- 0.3 vs 6.1 +/- 0.9 x 10(3) counts, P =.044), and
      oxidized low-density lipoprotein cholesterol (68 +/- 21 or 61 +/- 22 vs 59 +/- 20
      mg/dL, P =.039), after controlling for several potential confounders. An
      insignificant association was found between homocysteine (P =.08), C-reactive
      protein (P =.096), and the distribution of G894T polymorphism (P <.1). No
      association between the distribution of the polymorphism and hypertension status
      of the participants was observed. CONCLUSIONS: Our results imply that G894T
      polymorphism of the endothelial nitric oxide synthase gene is associated with
      elevated levels of inflammatory and oxidative stress markers, which may partially
      explain the increased prevalence of G894T polymorphism among patients with
      cardiovascular disease.

PMID- 15459609
TI  - Adjunctive effect of hyperbaric oxygen treatment after thrombolysis on left
      ventricular function in patients with acute myocardial infarction.
AB  - BACKGROUND: The role of hyperbaric oxygen in patients with acute myocardial
      infarction is controversial, ranging from not beneficial to having a favorable
      effect. This randomized study was conducted to further assess the benefit of
      hyperbaric oxygen treatment after thrombolysis on left ventricular function and
      remodeling in patients with acute myocardial infarction. METHODS: Seventy-four
      consecutive patients with first acute myocardial infarction were randomly
      assigned to treatment with hyperbaric oxygen treatment combined with
      streptokinase (HBO+) or streptokinase alone (HBO-). RESULTS: There was a
      significant decrease of end-systolic volume index from the first day to the third
      week in HBO+ patients compared with HBO- patients (from 30.40 to 28.18 vs from
      30.89 to 36.68 mL/m2, P <.05) accompanied with no changes of end-diastolic volume
      index in HBO+ compared with increased values in HBO- (from 55.68 to 55.10 vs from
      55.87 to 63.82 mL/m2, P <.05). Ejection fraction significantly improved in the
      HBO+ group and decreased in the HBO- group of patients after 3 weeks of acute
      myocardial infarction (from 46.27% to 50.81% vs from 45.54% to 44.05 %, P <.05).
      CONCLUSIONS: Adjunctive hyperbaric oxygen therapy after thrombolysis in acute
      myocardial infarction has a favorable effect on left ventricular systolic
      function and the remodeling process.

PMID- 15459610
TI  - Nicorandil improves cardiac function and clinical outcome in patients with acute
      myocardial infarction undergoing primary percutaneous coronary intervention: role
      of inhibitory effect on reactive oxygen species formation.
AB  - BACKGROUND: Early reperfusion therapy improves the clinical outcomes of patients
      with acute myocardial infarction (AMI), but benefits are limited by reperfusion
      injury in some patients. We examined the effect of nicorandil, a hybrid of K(ATP)
      channel opener and nicotinamide nitrate, on reactive oxygen species (ROS)
      formation and clinical outcomes after primary percutaneous coronary intervention
      (PCI) for AMI. METHODS: Fifty-eight patients with AMI were randomized into
      control (n = 25) and nicorandil pretreatment groups (n = 33). In the nicorandil
      group, nicorandil (4 mg as a bolus injection followed by constant infusion at 8
      mg/hour for 24 hours) was administered just after admission. ROS formation was
      assessed by measuring urinary excretion of 8-epi-prostaglandin F2alpha
      (PGF2alpha) and compared between the 2 groups. Cardiac function and the incidence
      of reperfusion injury and cardiac events were also compared. RESULTS: Urinary 8
      epi-PGF2alpha excretion was increased 2-fold at 60 to 90 minutes after PCI in the
      control group, whereas it was unchanged after PCI in the nicorandil group (P
      <.0001 between the 2 groups). The incidence of no-reflow phenomenon was lower in
      the nicorandil group than in the control group. Left ventricular ejection
      fraction and cardiac index at 6 months were greater in the nicorandil group than
      in controls. Plasma brain natriuretic peptide level at 6 months was lower in the
      nicorandil group. Incidences of inhospital cardiac events and rehospitalization
      were lower in the nicorandil group than in controls. CONCLUSIONS: Nicorandil
      improves cardiac function and clinical outcomes in patients with AMI. Suppression
      of ROS formation may be involved in the mechanism.

PMID- 15459611
TI  - Community trial to decrease ambulance diversion hours: the San Diego county
      patient destination trial.
AB  - STUDY OBJECTIVE: Emergency department (ED) ambulance diversion is a major issue
      in many communities. When patients do not reach requested facilities, challenges
      in care are compounded by lack of available medical records and delays in
      transferring admitted patients back to the originally requested facility. We seek
      to evaluate a community intervention to reduce ambulance diversion. METHODS: This
      was a community intervention in a county of 2.8 million individuals. Ambulance
      diversion guidelines were revised for all ambulance agencies and EDs.
      Participation by EDs was voluntary, and main outcome measures, which included
      ambulance transports, ambulance diversions, and bypass hours, were compared for
      the pretrial, trial, and posttrial periods. RESULTS: A total of 235,766 patients
      were transported to an ED by advanced life support ambulance during the 2-year
      study period. There was a significant decrease in the number of patients who did
      not reach the requested facility because of ambulance diversion for the trial
      period (n=322) and posttrial period (n=449) compared with the pretrial period
      (n=1,320; -998 diverted patients per month [95% confidence interval (CI) -1,162
      to -833 patients] and -871 diverted patients per month [95% CI -963 to -780
      patients], respectively). There was also a significant decrease in average
      monthly hours on diversion for the trial period (n=1,079) and posttrial period
      (n=1,774) compared with the pretrial period (n=4,007; -2,928 hours on bypass [95%
      CI -3,936 to -1,919 hours on bypass] and -2,232 hours on bypass [95% CI -3,620 to
      -2,235 hours on bypass], respectively). CONCLUSION: A voluntary community-wide
      approach to reducing hospital ED diversion and getting more ambulance patients to
      requested facilities was effective.

PMID- 15459612
TI  - Looking for a solution...to the solution?

PMID- 15459613
TI  - Limitations of difficult airway prediction in patients intubated in the emergency
      department.
AB  - STUDY OBJECTIVE: Physiognomic assessment of difficult laryngoscopy before rapid
      sequence intubation has been advocated for all emergency department (ED)
      intubations. The study objectives were to evaluate whether Mallampati scores,
      thyromental distance, and neck mobility could have been assessed in non-cardiac
      arrest ED-intubated patients and determine whether such tests would have been
      feasible in our rapid sequence intubation-associated laryngoscopy failures.
      METHODS: We retrospectively reviewed 37 months of ED intubations using
      prospectively collected data from electronic medical records, critical care flow
      sheets, and a trauma registry. All non-cardiac arrest ED-intubated patients were
      included for analysis. Mallampati scoring was deemed unobtainable if patients
      could not follow simple commands. Neck mobility and thyromental measurement were
      deemed unobtainable with cervical spine precautions. RESULTS: Eight hundred fifty
      intubations met the inclusion criteria, and 838 patients underwent rapid sequence
      intubation. Laryngoscopy failed in 3 patients who underwent rapid sequence
      intubation. Eight patients had awake nasal intubation, and 4 oral intubations
      were done without rapid sequence intubation. Four hundred fifty-two (53%)
      patients could not follow simple commands, and cervical spine immobilization was
      present in 370 (44%) patients. Only 32% of patients could follow simple commands
      and were not cervical spine immobilized. Among the 3 rapid sequence intubation
      laryngoscopy failures, no patients were following commands. CONCLUSION:
      Mallampati scoring, neck mobility testing, and measurement of thyromental
      distance could have been done in only one third of our non-cardiac arrest ED
      intubations and in none of the rapid sequence intubation failures. The inability
      to widely obtain these assessment tools, coupled with the low incidence of failed
      rapid sequence intubation, indicates limitations to using these screening tests
      in the ED setting.

PMID- 15459614
TI  - Assessing resident skills in the use of rescue airway devices.
AB  - STUDY OBJECTIVE: Airway control is a vital procedure for the specialty of
      emergency medicine. Although endotracheal intubation is the preferred method to
      obtain a definitive airway, several devices have been developed to help
      physicians handle a difficult or failed intubation. Using a bench model, we
      assessed the efficacy of an advanced airway training program. METHODS: Residents
      of an Accreditation Council for Graduate Medical Education-accredited 3-year
      emergency medicine residency program participated in an advanced airway course.
      Psychomotor skills were assessed for the laryngeal mask airway, intubating
      laryngeal mask airway (Fastrac), and Combitube (esophageal-tracheal twin-lumen
      airway device). The outcome variable was the time necessary to successfully
      insert and ventilate an airway mannequin. The skills were assessed at 0, 6, and
      12 months after training. Information including previous and interval experience
      with these devices was recorded. RESULTS: The airway mannequin was successfully
      ventilated using the laryngeal mask airway, Fastrac, and Combitube in 6.9, 51.0,
      and 21.5 seconds, respectively. There was a modest interval increase in mean time
      required to place the laryngeal mask airway and Combitube at 6 and 12 months
      after training. A decrease was noted in the time to place the Fastrac. Previous
      and interval experience did not affect performance. CONCLUSION: Airway competency
      is a key component of emergency medicine training. Training should include
      mastery of rescue devices for the failed or difficult airway. Our findings
      suggest that emergency medicine residents can learn and retain these airway
      skills.

PMID- 15459615
TI  - Tongue engorgement with prolonged use of the esophageal-tracheal Combitube.
AB  - We report a case of massive tongue engorgement associated with placement of an
      esophageal-tracheal twin-lumen airway device (Combitube) in a morbidly obese
      patient. Approximately 4 hours after atraumatic placement of the Combitube,
      tongue swelling occurred. An emergency tracheostomy was needed for airway
      management before removal of the Combitube. Ischemia-reperfusion injury or
      compression of glossal blood vessels, specifically lingual veins, was the most
      likely cause for the patient's tongue engorgement. An exhaustive search for other
      causes revealed nothing. Prolonged use of the Combitube may incur greater risk of
      airway complications such as tongue engorgement.

PMID- 15459616
TI  - Effect of education and guidelines for treatment of uncomplicated dental pain on
      patient and provider behavior.
AB  - STUDY OBJECTIVE: Patients with uncomplicated odontalgia use a significant
      proportion of emergency department (ED) resources. Some odontalgia patients are
      unaware that routine dental care is unavailable in most EDs. Using extensive
      input from regional dentists and oral surgeons, and after reviewing the dental
      literature, guidelines for the ED management of uncomplicated odontalgia were
      written for physician and patient use. The guidelines, which emphasize
      appropriate community dental clinic referrals and the use of nonsteroidal anti
      inflammatory drugs, were developed to reflect community standard of care. We
      hypothesize that patient education and treatment guidelines will decrease the
      number of ED visits, return visits, and narcotic prescriptions written for
      odontalgia. METHODS: This retrospective, observational study used primary
      International Classification of Diseases, Ninth Revision codes to identify visits
      for odontalgia during the year before and the year after guideline implementation
      in a tertiary care teaching hospital with 161,181 ED visits during the 2-year
      period of our study. RESULTS: There were 5,930 visits for odontalgia during the
      study. The proportion (95% confidence interval [CI]) of visits with odontalgia
      decreased after guideline implementation from 4.3% (95% CI 4.2% to 4.5%) to 3.1%
      (95% CI 3.0% to 3.2%). The proportion of patients with return visits decreased
      from 19.8% (95% CI 18.1% to 21.6%) to 9.2% (95% CI 7.9% to 10.8%). The proportion
      of patients filling narcotic prescriptions for odontalgia decreased from 29.6%
      (95% CI 28.1% to 31.2%) to 9.5% (95% CI 8.5% to 10.8%). CONCLUSION: Implementing
      odontalgia guidelines and providing patients with written information about
      alternative treatments and a list of dental clinics can reduce the burden of
      uncomplicated odontalgia on EDs that do not provide routine dental care.

PMID- 15459617
TI  - Care of the renal transplant recipient in the emergency department.
AB  - End-stage renal disease is becoming more common in the United States because of
      the aging of the population and the increased prevalence of predisposing
      conditions such as diabetes and hypertension. Renal transplantation is the
      preferred treatment for patients with end-stage renal disease. This article
      reviews the medical problems that might bring renal transplant recipients to the
      emergency department, the information emergency physicians should be aware of in
      evaluating and treating these patients, and the critical importance of close
      communication between emergency and transplant physicians in treating them.

PMID- 15459618
TI  - Clinical policy: evidence-based approach to pharmacologic agents used in
      pediatric sedation and analgesia in the emergency department.

PMID- 15459619
TI  - A patient education intervention does not improve satisfaction with emergency
      care.
AB  - STUDY OBJECTIVE: We determine whether a patient education intervention based on a
      previously validated model increases satisfaction with emergency department (ED)
      care. METHODS: A single-page patient education form was distributed on
      alternating 2-week time blocks for 8 weeks at the triage desk of a single
      academic ED. Alert, discharged patients were administered an exit interview
      assessing satisfaction on a 5-point ordinal scale. Secondary outcomes included
      patient satisfaction measured on a bivariate scale, willingness to return, and
      process of care indicators previously demonstrated to be associated with
      satisfaction. Exclusion criteria included air or ground transport to the ED,
      inability to speak English or Spanish, and refusal to participate. Differences in
      patient satisfaction and other outcomes were adjusted for predefined covariates,
      including age, sex, triage severity, race, language, location in ED, total ED
      length of stay, and time to room, using multivariable logistic regression.
      RESULTS: Of 1,934 patients discharged during study periods, 1,233 (64%) were
      approached and 860 (44%) were enrolled. There were no important covariate
      differences between the control and intervention groups. There was no important
      correlation between intervention and patient satisfaction on univariate (odds
      ratio [OR] 0.840; 95% confidence interval [CI] 0.650 to 1.086) and multivariate
      analysis (OR 0.874; 95% CI 0.672 to 1.136). There were no important correlations
      between the intervention and secondary outcomes on multivariate analysis.
      CONCLUSION: A triage-based, patient education intervention did not significantly
      improve patient satisfaction or performance on predictors of satisfaction at the
      study site.

PMID- 15459620
TI  - What should we do about patient satisfaction?

PMID- 15459621
TI  - Pneumococcal vaccination in the emergency department: an assessment of need.
AB  - STUDY OBJECTIVES: Immunization against Streptococcus pneumoniae with the 23
      valent pneumococcal polysaccharide vaccine has been shown to be cost-effective
      for prevention of invasive pneumococcal disease. Yet 23-valent pneumococcal
      polysaccharide vaccine is widely underused, particularly among ethnic minorities.
      The objectives of this survey are to determine the rate of 23-valent pneumococcal
      polysaccharide vaccine vaccination among all adult patients presenting to the
      emergency department (ED) of a county-based, urban, tertiary care medical center;
      the willingness of patients to receive 23-valent pneumococcal polysaccharide
      vaccine; and reasons for nonvaccination. METHODS: A quality assurance survey was
      performed in the ED during 3 days in September 2002. A survey was developed to
      determine 23-valent pneumococcal polysaccharide vaccine vaccination rates and
      eligibility according to indications and contraindications established by the
      Centers for Disease Control and Prevention (CDC). Descriptive statistics were
      performed to quantify the proportion of patients who were immunized, eligible,
      and willing to receive 23-valent pneumococcal polysaccharide vaccine and reasons
      for nonvaccination. RESULTS: A total of 250 patients of 1,535 registered in the
      ED were surveyed during the 3-day period. Only 48 (19%) had a primary care
      provider. The majority of patients were Hispanic (73%). Only 22 (9%) patients had
      received the vaccine. A total of 66 (26%) patients fit the CDC eligibility
      criteria for 23-valent pneumococcal polysaccharide vaccine, and 59 (89%) of these
      patients were willing to receive the vaccine during their ED visit. Most patients
      (79%) were eligible to receive 23-valent pneumococcal polysaccharide vaccine due
      to their comorbid illnesses. CONCLUSION: In the ED of our county-based urban
      medical center, 26% of patients were eligible for 23-valent pneumococcal
      polysaccharide vaccine; the majority of patients were Hispanic, unaware of the
      vaccine's existence, and willing to receive it during their ED visit. These data
      underscore a large unmet public health need among ethnic minorities in the ED.

PMID- 15459622
TI  - Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol)
      ingestion.
AB  - STUDY OBJECTIVE: Repeated supratherapeutic ingestion of acetaminophen is
      potentially lethal but poorly described. We provide the first prospective
      description of the characteristics, course, and outcome of patients with repeated
      supratherapeutic ingestion of acetaminophen. METHODS: This was a prospective case
      series of consecutive patients aged 12 years and older with acetaminophen dosage
      greater than 4 g per 24 hours referred to our poison center. Acetylcysteine was
      recommended if serum acetaminophen level exceeded 10 mg/L or aspartate
      aminotransferase exceeded 50 IU/L. Acetaminophen dosage, demographic factors,
      treatment, and outcome were recorded using standardized methods. Minimum follow
      up was 72 hours. RESULTS: Of 277 patients eligible, 249 patients were enrolled.
      At presentation, serum aspartate aminotransferase levels less than 50 IU/L were
      found in 126 patients, aspartate aminotransferase levels of 50 to 1,000 IU/L were
      present in 47 patients, and aspartate aminotransferase levels were above 1,000
      IU/L in 37 patients. No aspartate aminotransferase data were available for 39
      patients. No patient with an aspartate aminotransferase level below 50 IU/L at
      presentation developed hepatotoxicity (aminotransferase >1,000 IU/L). Seven (15%)
      patients with aspartate aminotransferase levels of 50 to 1,000 IU/L at
      presentation subsequently developed hepatotoxicity; 1 patient died. Six (16%)
      patients with aspartate aminotransferase levels above 1,000 IU/L at presentation
      died or received liver transplants. Study limitations included recall bias,
      incomplete patient follow-up, and the assumption that absence of clinical signs
      indicated insignificant liver injury. CONCLUSION: Our results suggest that the
      injury caused by acetaminophen repeated supratherapeutic ingestion is apparent at
      presentation and related to dose magnitude and duration. All patients who
      developed hepatotoxicity presented with aspartate aminotransferase above 50 IU/L.
      Determination of serum aspartate aminotransferase and acetaminophen
      concentrations may allow early discharge from the emergency department.

PMID- 15459623
TI  - Not enough relief from too much acetaminophen.

PMID- 15459624
TI  - Status epilepticus after a massive intravenous N-acetylcysteine overdose leading
      to intracranial hypertension and death.
AB  - Cases of N-acetylcysteine overdose have been reported before. In some cases,
      these overdoses have led to death if an anaphylactoid reaction was present. A
      healthy 30-month-old girl allegedly ingested acetaminophen at 418 mg/kg. Because
      the emergency physician feared the time of ingestion might not be accurate, he
      decided to start the 20.5-hour intravenous N-acetylcysteine protocol 8 hours
      after ingestion. He mistakenly prescribed the maximum milliliter-per-kilogram
      volume of the dextrose 5% diluent for the milliliter-per-kilogram volume of N
      acetylcysteine 20% to be administered. Five hours after the error was detected
      (19.5 hours postingestion), the patient started developing myoclonus on the left
      side of her body, with left eye deviation. This condition persisted
      intermittently for 3 hours despite treatment with diazepam, lorazepam, and
      phenytoin. A first computed tomographic scan result was normal. A few hours
      later, she sustained shorter recurrences of the myoclonus. At 30 hours after
      ingestion, she started to have irregular breathing and became unresponsive to
      pain. A repeated computed tomographic scan showed diffuse cerebral edema. A
      postmortem examination showed the presence of acute anoxic encephalopathy with
      marked cerebral edema and the beginning of uncal herniation that confirmed the
      clinical diagnosis of intracranial hypertension and brain death. A cumulative
      intravenous dose of 2,450 mg/kg of N -acetylcysteine was associated with status
      epilepticus, intracranial hypertension, and death in a child.

PMID- 15459625
TI  - Executive summary of the National Institute of Neurological Disorders and Stroke
      conference on Emergency Neurologic Clinical Trials Network.
AB  - On March 17 and 18, 2004, the National Institute of Neurological Disorders and
      Stroke sponsored a conference to explore the advisability of establishing a
      multicenter network designed to perform clinical trials in emergency neurologic
      conditions. The Emergency Neurology Clinical Trials Network concept was discussed
      by 25 clinicians and scientists from multiple disciplines. The goal was to
      improve the overall functional outcome for patients with acute neurologic
      emergencies. The participants discussed various aspects necessary in evaluating
      the potential of such a network, including the organization structure, funding,
      cost-effectiveness, and clinical conditions to be studied. A neurologic
      emergencies network that is not disease specific would open opportunities for
      clinical research that would facilitate rapid effective treatment of emergency
      conditions and lead to improved patient outcomes. In addition, the cost savings
      realized through economies of scale of such a network would allow more research
      to be performed at a lower cost.

PMID- 15459627
TI  - National Highway Traffic Safety Administation (NHTSA) Notes. Improving traffic
      safety among black communities.

PMID- 15459628
TI  - La farmacia.

PMID- 15459629
TI  - The idiopathic interstitial pneumonias.
AB  - This review includes the seven idiopathic interstitial pneumonias defined by The
      American Thoracic Society and The European Respiratory Society 2002 publication.
      Idiopathic pulmonary fibrosis is the clinical term for usual interstitial
      pneumonia. The radiologic pattern includes basal and subpleural ground glass and
      reticular opacities and honeycomb lung. Nonspecific interstitial pneumonia is
      characterized with a radiologic pattern of subpleural and basal ground glass and
      reticular opacities. Cryptogenic organizing pneumonia is manifest radiologically
      by peribronchial ground glass opacities and subpleural consolidation. Acute
      interstitial pneumonia is the clinical term for idiopathic diffuse alveolar
      damage and the exudative phase is characterized radiologically with diffuse
      ground glass opacification and dependent consolidation with the additional
      feature of lung architectural distortion in the organizing phase. Respiratory
      bronchiolitis associated interstitial lung disease manifests as centrilobular
      ground glass opacities on CT. Desquamative interstitial pneumonia is
      characterized by ground glass opacities with lower zone predominance on CT.
      Lymphoid interstitial pneumonia manifests by ground glass opacities and nodular
      interlobular septal thickening on CT. The diagnosis of an IIP should be rendered
      ideally only after all clinicoradiologic-pathologic data have been reviewed.

PMID- 15459630
TI  - Imaging of small-cell lung cancer.

PMID- 15459631
TI  - Radiological features of non-gastric mucosa-associated lymphoid tissue lymphomas.

PMID- 15459632
TI  - Septal thickening: HRCT findings and differential diagnosis.
AB  - Thickening of the interlobular septa is a common and easily recognized high
      resolution computed tomography feature of many diffuse lung diseases. In some
      cases, it is the predominant radiological finding. This article reviews the
      spectrum of entities that commonly present with thickening of the interlobular
      septa as the main radiological feature and establishes a practical approach for
      the differential diagnosis.

PMID- 15459641
TI  - Inpatient management of diabetes and hyperglycemia.

PMID- 15459643
TI  - Impact of genetically modified Enterobacter cloacae on indigenous endophytic
      community of Citrus sinensis seedlings.
AB  - Enterobacter cloacae (strain PR2/7), a genetically modified endophyte (GME) in
      citrus plants, carrying different plasmids (pEC3.0/18, pCelE, pEglA and pGFP),
      was inoculated into Citrus sinensis seedlings under greenhouse conditions. The
      impact of this on the indigenous bacterial endophytic community was studied by
      analyses of 2 different morphologic groups. The germination rates of inoculated
      seeds were evaluated in greenhouse, and plasmid stability under in vitro
      conditions. Results demonstrated a great and diverse endophytic community inside
      plants, and specialization in tissue colonization by some bacterial groups, in
      different treatments. Shifts in seed germination rate were observed among
      treatments: in general, the PR2/7 harboring pEglA bacterial clone significantly
      reduced seed germination, compared to the PR2/7 harboring pEC3.0/18 clone. This
      suggests that the presence of the pEglA plasmid changes bacteria-seed
      interactions. The endophytic community of citrus seedlings changed according to
      treatment. In seedlings treated with the PR2/7 with pEglA clone, the population
      of group II decreased significantly, within the context of the total endophytic
      community. These results indicate that the application of GMEs induces shifts in
      the endophytic bacterial community of citrus seedlings.

PMID- 15459644
TI  - Growth and physiological properties of wild type and mutants of Halomonas
      subglaciescola DH-1 in saline environment.
AB  - A halophilic bacterium was isolated from fermented seafood. The 16S rDNA sequence
      identity between the isolate and Halomonas subglaciescola AJ306801 was above 95%.
      The isolate that did not grow in the condition without NaCl or in the condition
      with other sodium (Na+) or chloride ions (Cl-) instead of NaCl was named H.
      subglaciescola DH-1. Two mutants capable of growing without NaCl were obtained by
      random mutagenesis, of which their total soluble protein profiles were compared
      with those of the wild type by two-dimensional electrophoresis. The external
      compatible solutes (betaine and choline) and cell extract of the wild type did
      not function as osmoprotectants, and these parameters within the mutants did not
      enhance their growth in the saline environment. In the proton translocation test,
      rapid acidification of the reactant was not detected for the wild type, but it
      was detected for the mutant in the condition without NaCl. From these results, we
      derived the hypothesis that NaCl may be absolutely required for the energy
      metabolism of H. subglaciescola DH-1 but not for its osmoregulation, and the
      mutants may have another modified proton translocation system that is independent
      of NaCl, except for those mutants with an NaCl-dependent system.

PMID- 15459645
TI  - Comparative analysis of cyanobacterial communities from polluted reservoirs in
      Korea.
AB  - Cyanobacteria are the dominant phototrophic bacteria in water environments. Here,
      the diversity of cyanobacteria in seven Korean reservoir waters where different
      levels of algal blooms were observed during the summer of 2002, was examined by T
      RFLP analysis. The number of T-RF bands in the HaeIII T-RFLP profiles analyzed
      from those water samples ranged from 20 to 44. Of these, cyanobacteria accounted
      for 6.1 to 27.2% of the total bacteria. The water samples could be clustered into
      2 groups according to the Dice coefficient of the T-RF profiles. The eutrophic
      Dunpo and oligotrophic Chungju reservoirs were selected, and several
      representative clones from both reservoir waters analyzed for the nucleotide
      sequences of their 16S rDNA. The major clones were found to belong to the
      Microcystis and Anabaena species in the waters from the Dunpo and Chungju
      reservoirs, respectively, which was in agreement with the T-RFLP result. That is,
      the Microcystis and Anabaena species were dominant in the eutrophic and polluted
      Dunpo and oligotrophic Chungju reservoir waters, respectively. These results
      indicated that there is a correlation between prevalence of cyanobacterial
      species and levels of pollution in reservoir waters.

PMID- 15459646
TI  - Genetic organization of the dhlA gene encoding 1,2-dichloroethane dechlorinase
      from Xanthobacter flavus UE15.
AB  - Xanthobacter flavus strain UE15 was isolated in wastewater obtained from the
      Ulsan industrial complex, Korea. This strain functions as a 1,2-dichloroethane
      (1,2-DCA) degrader, via a mechanism of hydrolytic dechlorination, under aerobic
      conditions. The UE15 strain was also capable of dechlorinating other
      chloroaliphatics, such as 2-chloroacetic acid and 2-chloropropionic acid. The
      dhlA gene encoding 1,2-DCA dechlorinase was cloned from the genomic DNA of the
      UE15 strain, and its nucleotide sequence was determined to consist of 933 base
      pairs. The deduced amino acid sequence of the DhlA dechlorinase exhibited 100%
      homology with the corresponding enzyme from X. autotrophicus GJ10, but only 27 to
      29% homology with the corresponding enzymes from Rhodococcus rhodochrous,
      Pseudomonas pavonaceae, and Mycobacterium sp. strain GP1, which all dechlorinate
      haloalkane compounds. The UE15 strain has an ORF1 (1,356 bp) downstream from the
      dhlA gene. The OFR1 shows 99% amino acid sequence homology with the transposase
      reported from X. autotrophicus GJ10. The transposase gene was not found in the
      vicinity of the dhlA in the GJ10 strain, but rather beside the dhlB gene coding
      for haloacid dechlorinase. The dhlA and dhlB genes were confirmed to be located
      at separate chromosomal loci in the Xanthobacter flavus UE15 strain as well as in
      X. autotrophicus GJ10. The dhlA and transposase genes of the UE15 strain were
      found to be parenthesized by a pair of insertion sequences, IS1247, which were
      also found on both sides of the transposase gene in the GJ10 strain. This unique
      structure of the dhlA gene organization in X. flavus strain UE15 suggested that
      the dechlorinase gene, dhlA, is transferred with the help of the transposase
      gene.

PMID- 15459647
TI  - Coregulation of lux genes and riboflavin genes in bioluminescent bacteria of
      Photobacterium phosphoreum.
AB  - Investigation of the expression of the riboflavin (rib) genes, which are found
      immediately downstream of luxG in the lux operon in Photobacterium phosphoreum,
      provides more information relevant to the evolution of bioluminescence, as well
      as to the regulation of supply of flavin substrate for bacterial bioluminescence
      reactions. In order to answer the question of whether or not the transcriptions
      of lux and rib genes are integrated, a transcriptional termination assay was
      performed with P. phosphoreum DNA, containing the possible stem-loop structures,
      located in the intergenic region of luxF and luxE (OmegaA), of luxG and ribE
      (OmegaB), and downstream of ribA (OmegaC). The expression of the CAT
      (Chloramphenicol Acetyl Transferase) reporter gene was remarkably decreased upon
      the insertion of the stem-loop structure (OmegaC) into the strong lux promoter
      and the reporter gene. However, the insertion of the structure (OmegaB) into the
      intergenic region of the lux and the rib genes caused no significant change in
      expression from the CAT gene. In addition, the single stranded DNA in the same
      region was protected by the P. phosphoreum mRNA from the S1 nuclease protection
      assay. These results suggest that lux genes and rib genes are part of the same
      operon in P. phosphoreum.

PMID- 15459648
TI  - A proteomic approach to study msDNA function in Escherichia coli.
AB  - Retron is a prokaryotic genetic element that produces multicopy single-stranded
      DNA covalently linked to RNA (msDNA) by a reverse transcriptase. It was found
      that cells producing a large amount of msDNA, rather than those that did not,
      showed a higher rate of mutation. In order to understand the molecular mechanism
      connecting msDNA production to the high mutation rate the protein patterns were
      compared by two dimensional gel electrophoresis. Ten proteins were found to be
      differentially expressed at levels more than three fold greater in cells with
      than without msDNA, nine of which were identified by MALDI TOF MS. Eight of the
      nine identified proteins were repressed in msDNA-producing cells and,
      surprisingly, most were proteins functioning in the dissimilation of various
      carbon sources. One protein was induced four fold greater in the msDNA producing
      cells and was identified as a 30S ribosomal protein S2 involved in the regulation
      of translation. The molecular mechanism underlying the elevated mutation in msDNA
      producing cell still remains elusive.

PMID- 15459649
TI  - Molecular cloning and characterization of CMCase gene (celC) from Salmonella
      typhimurium UR.
AB  - The sequence coding for carboxymethylcellulase (CMCase, CelC) was isolated from
      the DNA of Salmonella typhimurium UR1. Comparison between the deduced amino acid
      sequence of CelC (368 amino acid residues, Molecular mass 41 kDa) and that of the
      previously published CMCase revealed that this enzyme belongs to the cellulase
      family 8 and D. The protein was overproduced in Escherichia coli using T7
      expression system, and its activity was confirmed by CMC-SDS-PAGE. When the
      overexpressed CelC protein was tested on cellulose-type substrates, the
      recombinant protein is able to degrade cellulose-type substrates, such as CM
      cellulose, xylan, avicel, lichenan, and laminarin. Optimal temperature and pH for
      enzyme activity were found to be 50 degrees C and pH 6.5, respectively.

PMID- 15459650
TI  - Performance of the immunoglobulin G avidity and enzyme immunoassay IgG/IgM
      screening tests for differentiation of the clinical spectrum of toxoplasmosis.
AB  - Toxoplasmosis has been well known as an important human infection to consider
      especially in pregnant women. Although many serologic methods are available, the
      diagnosis of toxoplasmosis can be extremely difficult. The presence of increased
      levels of Toxoplasma-specific IgG antibodies indicates an infection, but it does
      not differentiate between a recent and past infection. The purpose of our study
      was to compare the performance of the ELISA T. gondii IgG/IgM test, a widely used
      enzyme-linked immunosorbent assay, to the ELISA IgG avidity method. One hundred
      and four serum samples (from 38 males and 66 females) were tested and evaluated
      from symptomatic patients (chorioretinitis, lymphadenopathy), and from women in
      their first trimester of pregnancy who were suspected of having toxoplasmosis.
      The high IgG avidity and ELISA IgG antibody levels were in agreement for 51 of
      the specimens (49.0%). Thirty-eight discrepant (borderline) results from the IgG
      avidity method were positive for IgM (3 specimens) and IgG (37 specimens).
      Interestingly, out of the eight serum samples that were positive for both IgG and
      IgM antibodies, two samples were low IgG avidity, and three samples were
      borderline. There was no statistically significant relation observed between the
      results of the IgG avidity method and the ELISA IgG test, and the IgG avidity
      method and ELISA IgM test (chi2 = 1.987; p = 0.370 and chi2 = 2.152; p = 0.341,
      respectively). The IgG avidity method was considered easy to perform and an
      acceptable approach for the differentiation of discrepant results
      (recent/chronic) and for the current detection of T. gondii antibodies. We
      concluded that the determination of IgG avidity is a helpful tool for the
      diagnosis of the ocular form of toxoplasmosis and it is a safe method for
      screening this disease in the first trimester of pregnancy.

PMID- 15459651
TI  - PCR method based on the ogdH gene for the detection of Salmonella spp. from
      chicken meat samples.
AB  - In a previous paper, the ogdH gene that encodes 2-oxoglutarate dehydrogenase was
      isolated from Salmonella typhimurium. The catalytic N-terminal region in the
      enzyme was found to be very specific for the Salmonella species. Therefore, the
      aim of the present study was to detect S. typhimurium in food sources using
      primers designed for OGDH-1 and OGDH-2 which were based on the salmonella
      specific region of the ogdH gene. A simple polymerase chain reaction (PCR)
      detection method was developed to detect low numbers of S. typhimurium in a
      chicken meat microbial consortium. Using the ogdH-specific primers under
      stringent amplification conditions and for gene probe analysis, fewer than 100
      colony-forming units (CFUs) were detectable when pure cultures were employed.
      When the PCR assay was run on S. typhimurium-contaminated meat contents, only the
      positive meat samples containing as few as 200 CFUs reacted to the assay. The
      method employed for sample processing is simple and it was determined to provide
      a sensitive means of detecting trace amounts of S. typhimurium-specific sequences
      in the presence of mixed meat microbial populations. When compared with six
      representative intestinal gram-negative bacterial strains in foods, including
      Vibrio parahaemolyticus, V. vulnificus, Enterobacter cloacae, E. coli O157:H7,
      Pseudomonas aeruginosa, and Proteus sp., S. typhimurium had a unique and distinct
      PCR product (796 bp). In conclusion, the two OGDH primers were found to be rapid
      and sensitive detectors of Salmonella spp for the PCR method.

PMID- 15459652
TI  - Isolation and characterization of alpha-glucosidase inhibitor from the fungus
      Ganoderma lucidum.
AB  - An alpha-glucosidase inhibitor, SKG-3, was isolated from the fruiting bodies of
      Ganoderma lucidum and its physico-chemical properties were characterized. It was
      a highly specific and effective reversible inhibitor of alpha-glucosidase. It
      showed very potent inhibitory activity against alpha-glucosidase with an IC50
      value of 4.6 micro g/ml, but no activity for any other glycosidases tested.
      Enzyme activity could be recovered upon dialysis, thus providing evidence for the
      reversibility of the inhibition. A Lineweaver-Burk plot indicated that the SKG-3
      inhibition of alpha-glucosidase was competitive.

PMID- 15459653
TI  - Purification of filamentous bacteriophage M13 by expanded bed anion exchange
      chromatography.
AB  - In this paper, we investigated the development of a simplified and rapid primary
      capture step for the recovery of M13 bacteriophage from particulate-containing
      feedstock. M13 bacteriophage, carrying an insert, was propagated and subsequently
      purified by the application of both conventional multiple steps and expanded bed
      anion exchange chromatography. In the conventional method, precipitation was
      conducted with PEG/NaCl, and centrifugation was also performed. In the single
      step expanded bed anion exchange adsorption, UpFront FastLine 20 (20 mm i.d.)
      from UpFront Chromatography was used as the contactor, while 54 ml (Ho = 15 cm)
      of STREAMLINE DEAE (rho = 1.2 g/cm3) from Amersham Pharmacia Biotechnology was
      used as the anion exchanger. The performance of the two methods were evaluated,
      analysed, and compared. It was demonstrated that the purification of the M13
      bacteriophage, using expanded bed anion exchange adsorption, yielded the higher
      recovery percentage, at 82.86%. The conventional multiple step method yielded the
      lower recovery percentage, 36.07%. The generic application of this integrated
      technique has also been assessed.

PMID- 15459654
TI  - Transcriptional regulation of the gene encoding gamma-glutamylcysteine synthetase
      from the fission yeast Schizosaccharomyces pombe.
AB  - Transcriptional regulation of the Schizosaccharomyces pombe gamma
      glutamylcysteine synthetase (GCS) gene was examined using the two GCS-lacZ fusion
      plasmids pUGCS101 and pUGCS102, which harbor 607 bp and 447 bp upstream regions,
      respectively. The negatively-acting sequence was located in the -607
      approximately -447 bp upstream region of the GCS gene. The upstream sequence
      responsible for induction by menadione (MD) and L-buthionine-(S, R)-sulfoximine
      (BSO) resides in the -607 approximately -447 bp region, whereas the sequence
      which codes for nitric oxide induction is located within the -447 bp region,
      measured from the translational initiation point. Carbon source-dependent
      regulation of the GCS gene appeared to be dependent on the nucleotide sequence
      within -447 bp region. The transcription factor Pap1 is involved in the induction
      of the GCS gene by MD and BSO, but not by nitric oxide. Induction of the GCS gene
      occurring due to low glucose concentration does not depend on the presence of
      Pap1. These data imply that induction by MD and BSO may be mediated by the Pap1
      binding site, probably located in the -607 approximately -447 region, and also
      that the nitric oxide-mediated regulation of the S. pombe GCS gene may share a
      similar mechanism with its carbon-dependent induction.

PMID- 15459655
TI  - Detection of hepatitis B virus and Mycobacterium tuberculosis in Korean dental
      patients.
AB  - This study examined the detection rate of the hepatitis B virus (HBV) and
      Mycobacterium tuberculosis (Mtb) in serum and saliva samples, respectively, from
      120 dental patients who were unaware if they have or had either hepatitis or
      tuberculosis. The frequencies of HBsAg and anti-HBs were determined using an
      immunochromatic assay. Mtb positivity was determined by the PCR method. Of the
      120 patients, 7 (5.8%) were HBV positive and 30 (25.0%) were Mtb positive. This
      highlights the fact that dental health care workers (DHCWs) can be exposed to the
      risk of infection from blood- or saliva-borne pathogens as a consequence of their
      work. Therefore, it is very important to prevent cross infection between patients
      and dental personnel. Accordingly, laboratory tests prior to surgical treatment
      are needed to determine the infectious state of dental patients in order to
      prevent the transmission of infectious diseases in dental clinics.

PMID- 15459656
TI  - Green fluorescent protein as a marker for monitoring a pentachlorophenol degrader
      Sphingomonas chlorophenolica ATCC39723.
AB  - Sphingomonas chlorophenolica ATCC39723 was successfully labeled with the gfp
      (green fluorescent protein) gene inserted into the pcpB gene by homologous
      recombination. As the gfp recombinant was easily distinguished from other
      indigenous organisms, the population of gfp recombinant was monitored after being
      released into the soil microcosms. Their population density dropped from 10(8) to
      10(6) (cfu/ml) in the non-sterilized soil microcosms during the first 6 days.
      Moreover, the gfp recombinant was not detected even at lower dilution rates after
      a certain time period. The recombinant, however, survived for at least 28 days in
      the sterilized soil microcosms. Although the gfp recombinant did not degrade
      pentachlorophenol (PCP), this experiment showed the possibility of using gfp as a
      monitoring reporter system for S. chlorophenolica ATCC39723 and potentially other
      species of Sphingomonas.

PMID- 15459657
TI  - Enhanced secretion of cell wall bound enolase into culture medium by the soo1-1
      mutation of Saccharomyces cerevisiae.
AB  - In order to identify the protein(s) secreted into culture medium by the soo1
      1/ret1-1 mutation of Saccharomyces cerevisiae, proteins from the culture medium
      of cells grown at permissive (28 degrees C) and non-permissive temperatures (37
      degrees C), were analyzed. Comparison of protein bands separated by SDS-PAGE
      identified a prominent band of 47-kDa band from a mutant grown at 37 degrees C. N
      terminal amino acid sequencing of this 47-kDa protein showed high identity with
      enolases 1 and 2. Western blot analysis revealed that most of the cell wall-bound
      enolase was released into the culture medium of the mutant grown at 37 degrees C,
      some of which were separated as those with lower molecular weights. Our results,
      presented here, indicate the impairment of cell wall enolase biogenesis and
      assembly by the soo1-1/ret1-1 mutation of S. cerevisiae.

PMID- 15459659
TI  - Pathways of chaperone-mediated protein folding in the cytosol.
AB  - Cells are faced with the task of folding thousands of different polypeptides into
      a wide range of conformations. For many proteins, the folding process requires
      the action of molecular chaperones. In the cytosol of prokaryotic and eukaryotic
      cells, molecular chaperones of different structural classes form a network of
      pathways that can handle substrate polypeptides from the point of initial
      synthesis on ribosomes to the final stages of folding.

PMID- 15459660
TI  - Checking on DNA damage in S phase.
AB  - The precise replication of the genome and the continuous surveillance of its
      integrity are essential for survival and the avoidance of various diseases. Cells
      respond to DNA damage by activating a complex network of the so-called checkpoint
      pathways to delay their cell-cycle progression and repair the defects. In this
      review we integrate findings on the emerging mechanisms of activation, the
      signalling pathways and the spatio-temporal organization of the intra-S-phase DNA
      damage checkpoint and its impact on the cell-cycle machinery, and discuss its
      biological significance.

PMID- 15459661
TI  - Connecting proliferation and apoptosis in development and disease.
AB  - Cells grow and divide rapidly during embryonic and postnatal development. Net
      tissue growth reflects the balance between the addition of new cells and the
      elimination of existing cells by programmed cell death. Cells compete for growth
      and survival factors to ensure an appropriate balance between the addition and
      elimination of cells. Elaborate mechanisms ensure that cells do not evade these
      constraints, and thereby prevent uncontrolled proliferation.

PMID- 15459662
TI  - Integrin signalling during tumour progression.
AB  - During progression from tumour growth to metastasis, specific integrin signals
      enable cancer cells to detach from neighbouring cells, re-orientate their
      polarity during migration, and survive and proliferate in foreign
      microenvironments. There is increasing evidence that certain integrins associate
      with receptor tyrosine kinases (RTKs) to activate signalling pathways that are
      necessary for tumour invasion and metastasis. The effect of these integrins might
      be especially important in cancer cells that have activating mutations, or
      amplifications, of the genes that encode these RTKs.

PMID- 15459663
TI  - Molecular mechanisms of translational control.
AB  - Translational control is widely used to regulate gene expression. This mode of
      regulation is especially relevant in situations where transcription is silent or
      when local control over protein accumulation is required. Although many examples
      of translational regulation have been described, only a few are beginning to be
      mechanistically understood. Instead of providing a comprehensive account of the
      examples that are known at present, we discuss instructive cases that serve as
      paradigms for different modes of translational control.

PMID- 15459664
TI  - Liver regeneration: from myth to mechanism.
AB  - The unusual regenerative properties of the liver are a logical adaptation by
      organisms, as the liver is the main detoxifying organ of the body and is likely
      to be injured by ingested toxins. The numerous cytokine- and growth-factor
      mediated pathways that are involved in regulating liver regeneration are being
      successfully dissected using molecular and genetic approaches. So what is known
      about this process at present and which questions remain?

PMID- 15459665
TI  - In search of the holy replicator.
AB  - After 40 years of searching for the eukaryotic replicator sequence, it is time to
      abandon the concept of 'the' replicator as a single genetic entity. Here I
      propose a 'relaxed replicon model' in which a positive initiator-replicator
      interaction is facilitated by a combination of several complex features of
      chromatin. An important question for the future is whether the positions of
      replication origins are simply a passive result of local chromatin structure or
      are actively localized to coordinate replication with other chromosomal
      activities.

PMID- 15459666
TI  - Imaging gene expression in single living cells.
AB  - Technical advances in the field of live-cell imaging have introduced the cell
      biologist to a new, dynamic, subcellular world. The static world of molecules in
      fixed cells has now been extended to the time dimension. This allows the
      visualization and quantification of gene expression and intracellular trafficking
      events of the studied molecules and the associated enzymatic processes in
      individual cells, in real time.

PMID- 15459667
TI  - A stepwise epigenetic process controls immunoglobulin allelic exclusion.
AB  - During the differentiation of T and B cells, immune-receptor loci in the genome
      must be made sterically accessible so that they can undergo rearrangement. Here,
      we discuss how this is carried out by the stepwise removal of epigenetic
      repression mechanisms - such as later-replication timing, heterochromatization,
      histone hypo-acetylation and DNA methylation - in a manner that initially favours
      one allele in each cell. We propose that this mechanism of allelic exclusion
      might also be the basis for the generation of gene diversity in other systems.

PMID- 15459668
TI  - IDO expression by dendritic cells: tolerance and tryptophan catabolism.
AB  - Indoleamine 2,3-dioxygenase (IDO) is an enzyme that degrades the essential amino
      acid tryptophan. The concept that cells expressing IDO can suppress T-cell
      responses and promote tolerance is a relatively new paradigm in immunology.
      Considerable evidence now supports this hypothesis, including studies of
      mammalian pregnancy, tumour resistance, chronic infections and autoimmune
      diseases. In this review, we summarize key recent developments and propose a
      unifying model for the role of IDO in tolerance induction.

PMID- 15459669
TI  - The multifaceted roles of TRAFs in the regulation of B-cell function.
AB  - Tumour-necrosis factor receptor (TNFR)-associated factors (TRAFs) are cytoplasmic
      adaptor proteins that are important in lymphocyte activation and apoptosis. Many
      studies of TRAFs have used models of exogenous overexpression by non-lymphoid
      cells. However, the actions of TRAFs present at normal levels in lymphoid cells
      often differ considerably from those that have been established in non-lymphocyte
      overexpression models. As I discuss here, information obtained from studying
      these molecules in physiological settings in B cells reveals that they have
      several roles, which are both unique and overlapping. These include activation of
      kinases and transcription factors, and interactions with other signalling
      proteins, culminating in the induction or inhibition of biological functions.

PMID- 15459670
TI  - Mast-cell responses to pathogens.
AB  - Mast cells have mainly been studied in the setting of allergic disease, but the
      importance of mast cells for host defence against several pathogens has now been
      well established. The location of mast cells, which are found closely associated
      with blood vessels, allows them to have a crucial sentinel role in host defence.
      The mast cell has a unique 'armamentarium' of receptor systems and mediators for
      responding to pathogen-associated signals. Studies of this intriguing immune
      effector cell provide important insights into the complex mechanisms by which
      appropriate innate and acquired immune responses are initiated.

PMID- 15459671
TI  - Gene therapy for autoimmune diseases: quo vadis?
AB  - Biological therapies using antibodies and cytokines are becoming widespread for
      the treatment of chronic inflammatory autoimmune diseases. However, these
      treatments have several limitations - such as expense, the need for repeated
      injections and unwanted side-effects - that can be overcome by genetic delivery.
      This review summarizes the ingenuity, sophistication and variety of gene-therapy
      approaches that have been taken in the design of therapeutic molecules and
      vectors, the engineering of cells and the regulation of gene expression for the
      targeting of disease outcome. We focus our attention on multiple sclerosis, type
      1 diabetes and rheumatoid arthritis.

PMID- 15459672
TI  - Immune responses to Listeria monocytogenes.
AB  - Listeria monocytogenes is a Gram-positive bacterium that is often used to study
      the mammalian immune response to infection because it is easy to culture, is
      relatively safe to work with and causes a highly predictable infection in
      laboratory mice. The broad application of this mouse model has resulted in a
      torrent of studies characterizing the contributions of different cytokines,
      receptors, adaptors and effector molecules to resistance against infection with
      Listeria monocytogenes. These studies, which are yielding one of the most
      comprehensive pictures of the 'battle' between host and microorganism, are
      reviewed here.

PMID- 15459673
TI  - A protective role for innate immunity in systemic lupus erythematosus.
AB  - Clinical and genetic studies in humans and animal models indicate a crucial
      protective role for the complement system in systemic lupus erythematosus (SLE).
      This presents a paradox because the complement system is considered to be an
      important mediator of the inflammation that is observed in patients with SLE. One
      current view is that complement provides protection by facilitating the rapid
      removal of apoptotic debris to circumvent an autoimmune response. In this Opinion
      article, I discuss an alternative model in which complement - together with other
      components of the innate immune system - participates in the 'presentation' of
      SLE-inducing self-antigens to developing B cells. In this way, the complement
      system and innate immunity protect against responses to SLE (self) antigens by
      enhancing the elimination of self-reactive lymphocytes.

PMID- 15459674
TI  - New drugs for asthma.
AB  - Asthma is a major and increasing global health problem and, despite major
      advances in therapy, many patients' symptoms are not adequately controlled.
      Treatment with combination inhalers, which contain a corticosteroid and long
      acting beta(2) adrenoceptor agonist, is the most effective current therapy. There
      is therefore a search for new therapies, particularly safe and effective oral
      treatments and those that are more efficacious in severe asthma. New therapies in
      development include mediator antagonists and inhibitors of cytokines, although
      these therapies might be too specific to be very effective. New anti-inflammatory
      therapies include corticosteroids and inhibitors of phosphodiesterase-4, p38
      mitogen-activated protein kinase and nuclear factor-kappaB. The prospects for a
      curative treatment are on the horizon.

PMID- 15459675
TI  - Bradykinin receptor ligands: therapeutic perspectives.
AB  - Kinins, which are produced by the action of kallikrein enzymes, are blood-derived
      local-acting peptides that have broad effects mediated by two related G-protein
      coupled receptors termed the bradykinin receptors. The endogenous kallikrein
      kinin system controls blood circulation and kidney function, and promotes
      inflammation and pain in pathological conditions, which has led to interest in
      developing modulators of bradykinin receptors as potential therapeutics. This
      review discusses recent progress in our understanding of the genetics, molecular
      biology and pathophysiology of kinins and their receptors, as well as
      developments in medicinal chemistry, which have brought us closer to therapeutic
      applications of kinin receptor ligands in various indications. The potential of
      kinin receptor antagonists as novel analgesic agents that do not result in
      tolerance or have a liability for abuse has attracted particular interest.

PMID- 15459676
TI  - The role of the medicinal chemist in drug discovery--then and now.
AB  - The role of the medicinal chemist in drug discovery has undergone major changes
      in the past 25 years, mainly because of the introduction of technologies such as
      combinatorial chemistry and structure-based drug design. As medicinal chemists
      with more than 50 years of combined experience spanning the past four decades, we
      discuss this changing role using examples from our own and others' experience.
      This historical perspective could provide insights in to how to improve the
      current model for drug discovery by helping the medicinal chemist regain the
      creative role that contributed to past successes.

PMID- 15459677
TI  - Glycomics: a pathway to a class of new and improved therapeutics.
AB  - Complex glycans that are located at the surface of cells, deposited in the
      extracellular matrix and attached to soluble signalling molecules have a crucial
      role in the phenotypic expression of cellular genotypes. However, owing to their
      structural complexity and some redundancy in terms of structures that elicit a
      function, the therapeutic potential of complex glycans has not been well
      exploited, with a few notable exceptions. This review outlines recent advances
      that promise to increase our ability to use complex glycans as therapeutics.
      Opportunities for the development of further structure-function relationships for
      these complex molecules are also discussed.

PMID- 15459678
TI  - Prion diseases--close to effective therapy?
AB  - The transmissible spongiform encephalopathies could represent a new mode of
      transmission for infectious diseases--a process more akin to crystallization than
      to microbial replication. The prion hypothesis proposes that the normal isoform
      of the prion protein is converted to a disease-specific species by template
      directed misfolding. Therapeutic and prophylactic strategies to combat these
      diseases have emerged from immunological and chemotherapeutic approaches. The
      lessons learned in treating prion disease will almost certainly have an impact on
      other diseases that are characterized by the pathological accumulation of
      misfolded proteins.

PMID- 15459679
TI  - Strategies to facilitate the development of new contraceptives.
AB  - Contraception is not readily accessible to much of the world's population and, in
      any case, no method is 100% effective or appropriate for all users. There is a
      pressing need for new methods to address the diverse requirements of the global
      community of men and women at all stages of their reproductive lives. This
      article will look at some of the new opportunities in contraceptive research and
      highlight strategies to overcome old challenges for the development of novel
      contraceptives.

PMID- 15459680
TI  - Roadblocks to cancer cures.

PMID- 15459681
TI  - Therapeutic cloning gives silenced genes a second voice.

PMID- 15459683
TI  - Scientists stumped by dual push for open access, secrecy.

PMID- 15459685
TI  - Ethical quagmire awaits vaccine for cocaine addiction.

PMID- 15459686
TI  - Inflamed brains can trigger the blues, studies suggest.

PMID- 15459688
TI  - Profile: John Hardy.

PMID- 15459689
TI  - Mood swings.

PMID- 15459690
TI  - Transgenic mouse model for monitoring endoplasmic reticulum stress in vivo.

PMID- 15459692
TI  - Towering science: an ounce of creativity is worth a ton of impact.

PMID- 15459693
TI  - From chemical warfare to breast cancer management.

PMID- 15459694
TI  - A transcriptional basis for physiology.

PMID- 15459695
TI  - How I became one of the fathers of a superfamily.

PMID- 15459696
TI  - How a jolt and a bolt in a dentist's chair revolutionized cataract surgery.

PMID- 15459697
TI  - Explorations in the land of DNA and beyond.

PMID- 15459700
TI  - VEGF obstructs the lungs.

PMID- 15459701
TI  - Hematopoietic stem cells get closer to the bone.

PMID- 15459702
TI  - Bone marrow spawns brain killers.

PMID- 15459703
TI  - Memory may not need reminding.

PMID- 15459704
TI  - Suppressing the self in rheumatoid arthritis.

PMID- 15459705
TI  - Nutrient sensor links obesity with diabetes risk.

PMID- 15459706
TI  - HIV's lair.

PMID- 15459707
TI  - Easing the brakes on spinal cord repair.

PMID- 15459709
TI  - Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic
      breakthroughs.
AB  - A wide variety of neurodegenerative diseases are characterized by the
      accumulation of intracellular or extracellular protein aggregates. More recently,
      the genetic identification of mutations in familial counterparts to the sporadic
      disorders, leading to the development of in vitro and in vivo model systems, has
      provided insights into disease pathogenesis. The effect of many of these
      mutations is the abnormal processing of misfolded proteins that overwhelms the
      quality-control systems of the cell, resulting in the deposition of protein
      aggregates in the nucleus, cytosol and/or extracellular space. Further
      understanding of mechanisms regulating protein processing and aggregation, as
      well as of the toxic effects of misfolded neurodegenerative disease proteins,
      will facilitate development of rationally designed therapies to treat and prevent
      these disorders.

PMID- 15459713
TI  - Images to reveal all?

PMID- 15459715
TI  - GSK-3beta sets Snail's pace.

PMID- 15459716
TI  - Crossing the tracks.

PMID- 15459717
TI  - Refocusing on BRCA1.

PMID- 15459718
TI  - Hauling t-SNAREs on the microtubule highway.

PMID- 15459719
TI  - Nuclear transfer: epigenetics pays a visit.

PMID- 15459720
TI  - Maintaining integrity.
AB  - Research on genome stability and integrity now extends far beyond the
      biochemistry of DNA repair to encompass signal transduction pathways that span
      numerous aspects of cellular life. Derailed genomic integrity pathways can result
      in debilitating genetic disorders, premature ageing, predisposition to cancer and
      degenerative conditions. Current progress in this rapidly expanding field was the
      subject of an EMBO workshop, Maintenance of Genomic Integrity, that took place in
      June 2004 in Galway, Ireland. Top

PMID- 15459721
TI  - Microtubules in mouse neurons.

PMID- 15459722
TI  - Syntabulin is a microtubule-associated protein implicated in syntaxin transport
      in neurons.
AB  - Different types of cargo vesicles containing presynaptic proteins are transported
      from the nerve cell body to the nerve terminal, and participate in the formation
      of active zones. However, the identity of the membranous cargoes and the nature
      of the motor-cargo interactions remain unsolved. Here, we report the
      identification of a syntaxin-1-binding protein named syntabulin. Syntabulin
      attaches syntaxin-containing vesicles to microtubules and migrates with syntaxin
      within the processes of hippocampal neurons. Knock-down of syntabulin expression
      with targeted small interfering RNAs (siRNAs) or interference with the syntabulin
      syntaxin interaction inhibit attachment of syntaxin-cargo vesicles to
      microtubules and reduce syntaxin-1 distribution in neuronal processes.
      Furthermore, conventional kinesin I heavy chain binds to syntabulin and
      associates with syntabulin-linked syntaxin vesicles in vivo. These findings
      suggest that syntabulin functions as a linker molecule that attaches syntaxin
      cargo vesicles to kinesin I, enabling the transport of syntaxin-1 to neuronal
      processes.

PMID- 15459726
TI  - Science policy for risk governance.

PMID- 15459727
TI  - Pascal's legacy.

PMID- 15459728
TI  - Globalization and risks to health.

PMID- 15459729
TI  - The real and perceived risks of genetically modified organisms.

PMID- 15459731
TI  - The risks of eating and drinking.

PMID- 15459730
TI  - The prediction of disease risk in genomic medicine.

PMID- 15459732
TI  - The case of nanobiotechnology.

PMID- 15459733
TI  - Hormesis: a revolution in toxicology, risk assessment and medicine.

PMID- 15459734
TI  - Systemic risks: a new challenge for risk management.

PMID- 15459735
TI  - Principles of risk perception applied to gene technology.

PMID- 15459736
TI  - Science in a political environment.

PMID- 15459737
TI  - The consequences of fear.

PMID- 15459738
TI  - When even the 'best-laid' plans go wrong.

PMID- 15459739
TI  - Risk and the law.

PMID- 15459740
TI  - Open access and closed options.

PMID- 15459741
TI  - Are microbes at the root of a solution to world food production? Rational
      exploitation of interactions between microbes and plants can help to transform
      agriculture.

PMID- 15459742
TI  - The future of stem-cell research in Germany. A Delphi study.

PMID- 15459743
TI  - Science policy in the USA. Sweeping changes to government science under the Bush
      administration may have caused long-term damage, scientists fear.

PMID- 15459744
TI  - Accession without concession. The ten new EU member states have an uphill battle
      to improve their science base, but would prefer not to play by different rules
      from the rest.

PMID- 15459745
TI  - Hormone therapy for the ageing. Despite the negative results of recent trials,
      hormone replacement therapy retains enticing promises for the elderly.

PMID- 15459746
TI  - Daughter-specific repression of Saccharomyces cerevisiae HO: Ash1 is the
      commander.
AB  - The GATA-1-like factor Ash1 is a repressor of the HO gene, which encodes an
      endonuclease that is responsible for mating-type switching in the yeast
      Saccharomyces cerevisiae. A multi-step programme, which involves a macromolecular
      protein complex, the secondary structure of ASH1 mRNA and the cell cytoskeleton,
      enables Ash1 to asymmetrically localize to the daughter cell nucleus in late
      anaphase and to repress HO transcription. The resulting Ash1 activity prevents
      the daughter cell from switching mating type. How does Ash1 inhibit transcription
      of HO exclusively in the daughter cell? In this review, a speculative model is
      proposed and discussed. Through its action as a daughter-specific repressor, Ash1
      can be considered to be an ancestral regulator of cell fate in eukaryotes.

PMID- 15459747
TI  - Huntingtin and the molecular pathogenesis of Huntington's disease. Fourth in
      molecular medicine review series.
AB  - Huntington's disease (HD) is a late-onset neurodegenerative disorder that is
      caused by a CAG repeat expansion in the IT15 gene, which results in a long
      stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin
      (htt). The normal function of htt, and the molecular mechanisms that contribute
      to the disease pathogenesis, are in the process of being elucidated. In this
      review, we outline the potential functions of htt as defined by the proteins with
      which it has been found to interact. We then focus on evidence that supports a
      role for transcriptional dysfunction and impaired protein folding and degradation
      as early events in disease pathogenesis.

PMID- 15459748
TI  - In control: systematic assessment of microarray performance.
AB  - Expression profiling using DNA microarrays is a powerful technique that is widely
      used in the life sciences. How reliable are microarray-derived measurements? The
      assessment of performance is challenging because of the complicated nature of
      microarray experiments and the many different technology platforms. There is a
      mounting call for standards to be introduced, and this review addresses some of
      the issues that are involved. Two important characteristics of performance are
      accuracy and precision. The assessment of these factors can be either for the
      purpose of technology optimization or for the evaluation of individual microarray
      hybridizations. Microarray performance has been evaluated by at least four
      approaches in the past. Here, we argue that external RNA controls offer the most
      versatile system for determining performance and describe how such standards
      could be implemented. Other uses of external controls are discussed, along with
      the importance of probe sequence availability and the quantification of labelled
      material.

PMID- 15459750
TI  - Granulocyte macrophage-colony stimulating factor and interleukin-3 increase
      expression of type II tumour necrosis factor receptor, increasing susceptibility
      to tumour necrosis factor-induced apoptosis. Control of leukaemia cell life/death
      switching.
AB  - Tumour necrosis factor (TNF) induces apoptosis in a range of cell types via its
      two receptors, TNFR1 and TNFR2. Here, we demonstrate that proliferation and TNFR2
      expression was increased in human leukaemic TF-1 cells by granulocyte macrophage
      colony stimulating factor (GM-CSF) and interleukin-3 (IL-3), with TNFR1
      expression unaffected. Consequently, they switch from a proliferative to a TNF
      induced apoptotic phenotype. Raised TNFR2 expression and susceptibility to TNF
      induced apoptosis was not a general effect of proliferation as IL-1beta and IFN
      gamma both proliferated TF-1 cells with no effect on TNFR expression or
      apoptosis. Although raised TNFR2 expression correlated with the apoptotic
      phenotype, stimulation of apoptosis in GM-CSF-pretreated cells was mediated by
      TNFR1, with stimulation of TNFR2 alone insufficient to initiate cell death.
      However, TNFR2 did play a role in apoptotic and proliferative responses as they
      were blocked by the presence of an antagonistic TNFR2 antibody. Additionally,
      coincubation with cycloheximide blocked the mitotic effects of GM-CSF or IL-3,
      allowing only the apoptotic responses of TNF to persist. TNF life/death was also
      observed in K562, but not MOLT-4 and HL-60 human leukaemic cell types. These
      findings show a cooperative role of TNFR2 in the TNF life/death switching
      phenomenon.

PMID- 15459751
TI  - RB and RB2/p130 genes demonstrate both specific and overlapping functions during
      the early steps of in vitro neural differentiation of marrow stromal stem cells.
AB  - Marrow stromal stem cells (MSCs) are stem-like cells that are currently being
      tested for their potential use in cell therapy for a number of human diseases.
      MSCs can differentiate into both mesenchymal and nonmesenchymal lineages. In
      fact, in addition to bone, cartilage and fat, it has been demonstrated that MSCs
      are capable of differentiating into neurons and astrocytes. RB and RB2/p130 genes
      are involved in the differentiation of several systems. For this reason, we
      evaluated the role of RB and RB2/p130 in the differentiation and apoptosis of
      MSCs under experimental conditions that allow for MSC differentiation toward the
      neuron-like phenotype. To this end, we ectopically expressed either RB or
      RB2/p130 and monitored proliferation, differentiation and apoptosis in rat
      primary MSC cultures induced to differentiate toward the neuron-like phenotype.
      Both RB and RB2/P130 decreased cell proliferation rate. In pRb-overexpressing
      cells, the arrest of cell growth was also observed in the presence of the HDAC
      inhibitor TSA, suggesting that its antiproliferative activity does not rely upon
      the HDAC pathway, while the addition of TSA to pRb2/p130-overexpressing cells
      relieved growth inhibition. TUNEL reactions and studies on the expression of
      genes belonging to the Bcl-2 family showed that while RB protected
      differentiating MSCs from apoptosis, RB2/p130 induced an increase of apoptosis
      compared to controls. The effects of both RB and RB2/p130 on programmed cell
      death appeared to be HDAC- independent. Molecular analysis of neural
      differentiation markers and immunocytochemistry revealed that RB2/p130
      contributes mainly to the induction of generic neural properties and RB triggers
      cholinergic differentiation. Moreover, the differentiation potentials of RB2/p130
      and RB appear to rely, at least in part, on the activity of HDACs.

PMID- 15459752
TI  - Neuroprotective effects and intracellular signaling pathways of erythropoietin in
      a rat model of multiple sclerosis.
AB  - In multiple sclerosis (MS), long-term disability is primarily caused by axonal
      and neuronal damage. We demonstrated in a previous study that neuronal apoptosis
      occurs early during experimental autoimmune encephalomyelitis, a common animal
      model of MS. In the present study, we show that, in rats suffering from myelin
      oligodendrocyte glycoprotein (MOG)-induced optic neuritis, systemic application
      of erythropoietin (Epo) significantly increased survival and function of retinal
      ganglion cells (RGCs), the neurons that form the axons of the optic nerve. We
      identified three independent intracellular signaling pathways involved in Epo
      induced neuroprotection in vivo: Protein levels of phospho-Akt, phospho-MAPK 1
      and 2, and Bcl-2 were increased under Epo application. Using a combined treatment
      of Epo together with a selective inhibitor of phosphatidylinositol 3-kinase (PI3
      K) prevented upregulation of phospho-Akt and consecutive RGC rescue. We conclude
      that in MOG-EAE the PI3-K/Akt pathway has an important influence on RGC survival
      under systemic treatment with Epo.

PMID- 15459753
TI  - Water induces autocrine stimulation of tumor cell killing through ATP release and
      P2 receptor binding.
AB  - Although exposure of cells to extreme hypotonic stress appears to be a purely
      experimental set up, it has found an application in clinical routine. For years,
      surgeons have washed the abdominal cavity with distilled water to lyse isolated
      cancer cells left after surgery. No data are available supporting this practice
      or evaluating the potential mechanisms of cell injury under these circumstances.
      Recent evidence indicates that increases in cell volume stimulate release of
      adenosine triphosphate and autocrine stimulation of purinergic (P2) receptors in
      the plasma membrane of certain epithelial cell types. Under physiological
      conditions, purigenic stimulation can contribute to cell volume recovery through
      activation of solute efflux. In addition, adenosine triphosphate-P2 receptor
      binding might trigger other mechanisms affecting cell viability after profound
      hypotonic stress. This study demonstrates a novel pathway of cell death by
      apoptosis in human colon cancer cells following a short hypotonic stress. This
      pathway is induced by transitory cell swelling which leads to extracellular
      release of adenosine triphosphate (ATP) and specific binding of ATP to P2
      receptors (probably P2X7). Extracellular ATP induced activation of caspases 3 and
      8, annexin V, release of cytochrome c, and eventually cell death. The effect of
      ATP can be blocked by addition of (i) apyrase to hydrolyse extracellular ATP and
      (ii) suramin, a P2 receptor antagonist. Finally, (iii) gadolinium pretreatment, a
      blocker of ATP release, reduces sensitivity of the cells to hypotonic stress. The
      adenosine triphosphate-P2 receptor cell death pathway suggests that
      autocrine/paracrine signaling may contribute to regulation of viability in
      certain cancer cells disclosed with this pathway.

PMID- 15459754
TI  - Distinct thymocyte subsets express the vanilloid receptor VR1 that mediates
      capsaicin-induced apoptotic cell death.
AB  - Herein, we provide the first evidence on the capsaicin (CPS) receptor vanilloid
      receptor type-1 (VR1) by rat thymocytes, and its involvement in CPS-induced
      apoptosis. VR1 mRNA was identified by quantitative RT-PCR in CD5(+) thymocytes.
      By immunofluorescence and flow cytometry, we found that a substantial portion of
      CD5+ thymocytes, namely CD4+ and double negative (DN) cell subsets, express VR1
      that was present on plasma membrane on discrete spots. By Western blot, VR1
      protein was identified as a single band of 95 kDa. We also described that CPS
      could trigger two distinct pathways of thymocyte death, namely apoptosis and
      necrosis depending on the dose of CPS exposure. CPS-induced apoptosis involved
      intracellular free calcium (Ca2+) influx, phosphatidylserine exposure,
      mitochondrial permeability transmembrane pore (PTP) opening and mitochondrial
      transmembrane potential (Delta Psi m) dissipation leading to cytochrome c
      release, activation of caspase-9 and -3 and oligonucleosomal DNA fragmentation.
      VR1 was functionally implicated in these events as they were completely abrogated
      by the VR1 antagonist, capsazepine (CPZ). Finally, we demonstrated that VR1
      expression on distinct thymocytes was associated with the selective ability of
      CPS to trigger DNA fragmentation in VR1+ CD4+ and DN thymocytes. Overall, our
      results suggest that the expression of VR1 on thymocytes may function as a sensor
      of harmful stimuli present in the thymic environment.

PMID- 15459756
TI  - Loss of co-linearity by modular polyketide synthases: a mechanism for the
      evolution of chemical diversity.
AB  - Modular polyketide synthases biosynthesise natural products through successive
      Claisen-type condensations, where one module is responsible for one round of
      chain extension. This review describes recent findings where this rule of co
      linearity is broken, either by one module being bypassed (skipping) or through
      one module being used for multiple chain extension events (stuttering).

PMID- 15459755
TI  - Molecular signatures of proliferation and quiescence in hematopoietic stem cells.
AB  - Stem cells resident in adult tissues are principally quiescent, yet harbor
      enormous capacity for proliferation to achieve self renewal and to replenish
      their tissue constituents. Although a single hematopoietic stem cell (HSC) can
      generate sufficient primitive progeny to repopulate many recipients, little is
      known about the molecular mechanisms that maintain their potency or regulate
      their self renewal. Here we have examined the gene expression changes that occur
      over a time course when HSCs are induced to proliferate and return to quiescence
      in vivo. These data were compared to data representing differences between
      naturally proliferating fetal HSCs and their quiescent adult counterparts.
      Bioinformatic strategies were used to group time-ordered gene expression profiles
      generated from microarrays into signatures of quiescent and dividing stem cells.
      A novel method for calculating statistically significant enrichments in Gene
      Ontology groupings for our gene lists revealed elemental subgroups within the
      signatures that underlie HSC behavior, and allowed us to build a molecular model
      of the HSC activation cycle. Initially, quiescent HSCs evince a state of
      readiness. The proliferative signal induces a preparative state, which is
      followed by active proliferation divisible into early and late phases. Re
      induction of quiescence involves changes in migratory molecule expression, prior
      to reestablishment of homeostasis. We also identified two genes that increase in
      both gene and protein expression during activation, and potentially represent new
      markers for proliferating stem cells. These data will be of use in attempts to
      recapitulate the HSC self renewal process for therapeutic expansion of stem
      cells, and our model may correlate with acquisition of self renewal
      characteristics by cancer stem cells.

PMID- 15459757
TI  - Terpenoids of Aristolochia and their biological activities.
AB  - Aristolochia is an important genus widely used in traditional medicine. During
      the past two decades, this genus has attracted much interest and has been the
      subject of numerous chemical and pharmacological studies. It is a rich source of
      aristolochic acids, which are unique to this genus, and of terpenoids. The nature
      of these terpenoids are reviewed in this article together with some bioactivity
      data in an effort to highlight the rapid development in the field of
      phytochemistry of the Aristolochia species.

PMID- 15459758
TI  - Indolizidine and quinolizidine alkaloids.
AB  - This review covers the isolation, structure determination, synthesis, chemical
      transformations and biological activity of indolizidine and quinolizidine
      alkaloids from microbial, plant and animal sources. Included in the review are
      the hydroxylated indolizidines lentiginosine, swainsonine, castanospermine and
      their analogues; alkaloids from animal sources, including ants, amphibians and
      beetles; ipalbidine, phenanthroindolizidines and related alkaloids; Lycopodium
      alkaloids; lupine alkaloids; and alkaloids from bacterial and marine sources. The
      literature from July 2002 to June 2003 is reviewed, and 174 references are cited.

PMID- 15459759
TI  - Quinoline, quinazoline and acridone alkaloids.
AB  - This review covers the isolation, structure determination, synthesis and
      biological activity of quinoline, quinazoline and acridone alkaloids from plant,
      microbial and animal sources. The literature from July 2002 to June 2003 is
      reviewed, and 119 references are cited.

PMID- 15459760
TI  - Natural sesquiterpenoids.
AB  - This review covers the isolation, structural determination, synthesis and
      chemical and microbiological transformations of natural sesquiterpenoids. The
      literature from January to December 2003 is reviewed, and 389 references are
      cited.

PMID- 15459762
TI  - [Aortic valve stenosis].
AB  - Aortic valve stenosis is the most frequent reason for prosthetic valve
      replacement in adults. Its incidence increases with age. Development of the most
      frequent form, degenerative-calcific aortic stenosis, is related to
      atherosclerotic risk factors. The narrowing of the aortic valve orifice leads to
      creation of a systolic pressure drop, the gradient, between left ventricle and
      ascending aorta. The pressure overload from aortic stenosis causes concentric
      left ventricular hypertrophy and later heart failure. Typical symptoms of severe
      aortic stenosis include dyspnea, angina, and dizziness or syncope. On
      auscultation, a loud systolic murmur over the base of the heart is apparent,
      which is transmitted to the carotids. The ECG often shows left ventricular
      hypertrophy. The most important diagnostic technique is echocardiography, which
      allows to measure the gradient and to calculate the orifice area, which determine
      the degree of severity. The development of symptoms or impaired left ventricular
      function in severe aortic stenosis should prompt surgical treatment by valve
      replacement. Truly asymptomatic patients with preserved left ventricular function
      should be followed conservatively.

PMID- 15459763
TI  - [Additive treatment for central vestibular vertigo].
AB  - We have observed in our own practice that numerous patients with primary symptoms
      of vertigo exhibit cervical segmental muscular imbalance and increased tension in
      the masticatory musculature. This is frequently associated with functional
      blockades, especially in the joints of the head and upper cervical spine.
      Particularly important are special receptors of the small vertebral joints and
      muscle insertions at the cervicocranial transition. Evidence indicates that there
      are neuroanatomic structures between these receptors and the central vestibular
      and cochlear core area of the brain stem, which can explain the vertigo symptoms
      as well as the frequently associated tinnitus, headache or otalgia. Therapeutic
      approaches include interruption of the pathological reflex arcs so that muscle
      tension can resolve and imbalances are equalized. The nociceptive stimulus to the
      brain stem and its core centers thus recedes. Deafferentation follows from the
      reflex zones of the posterior oral cavity in the sense of oral acupuncture.
      Additional procedures include neural therapeutic injections at acupuncture points
      at the cervicocranial transition, the ear, and maxillary area as well as needle
      acupuncture of the head, ear, and hand. In isolated cases, improvement of the
      vertigo symptoms is noticed as early as after the first treatment session. Among
      other methods, spinovestibular tests according to Romberg and Unterberger can be
      employed to objectify treatment results.

PMID- 15459764
TI  - The important role for betaVLDLs binding at the fourth cysteine of first ligand
      binding domain in the low-density lipoprotein receptor.
AB  - The low-density lipoprotein (LDL) receptor (LDLR) is a crucial role for binding
      and uptaking apolipoprotein (apo) B-containing lipoproteins, such as very-low
      density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and LDL. The
      defect function of the LDLR causes familial hypercholesterolemia (FH), the
      phenotype of which is elevated plasma cholesterol and premature coronary heart
      disease (CHD). In the present study, we characterize the role of the cysteine
      residue of the ligand-binding domain of the LDLR. The mutant LDLR protein of
      cysteine for serine at codon 25 (25S-LDLR) was expressed in Chinese hamster ovary
      (CHO) cell line, ldl-A7. By Western blot analysis, the 25S-LDLR was detected with
      monoclonal antibody IgG-12D10, which reacts with the linker site of the LDLR but
      not with IgG-C7, which reacts with the NH2 terminus of the receptor. The 25S-LDLR
      bound LDL similarly to the wild-type LDLR, but the rate of uptake of LDL by the
      mutant receptor was only about half of that by the wild-type receptor. In
      contrast, the 25S-LDLR bound and internalized beta VLDL more avidly than LDL.
      These results suggest that the fourth cysteine residue of the first ligand
      binding domain of the LDLR might be important for the internalization of
      atherogenic lipoproteins by vascular cells despite reduced LDL uptake, leading to
      atherosclerosis and premature cardiovascular disease.

PMID- 15459765
TI  - Thyrotoxic crisis induced by cytotoxic chemotherapy.
AB  - Thyroid storm is a rare and life-threatening medical emergency. We report a young
      lady with Graves' disease and acute myeloid leukaemia who developed thyrotoxic
      crisis following an induction course of chemotherapy given for the treatment of
      acute leukaemia. After successful management of her leukaemia and thyroid
      disease, she received an autologous bone marrow transplantation.

PMID- 15459766
TI  - Oxytocin, oxytocin-associated neurophysin and the oxytocin receptor in the human
      prostate.
AB  - Oxytocin has been implicated in the regulation of prostate growth. However, the
      cellular localisation of oxytocin in the normal and diseased human prostate is
      not known. Oxytocin, oxytocin-associated neurophysin and oxytocin receptor were
      detected by immunohistochemistry in tissues from patients undergoing routine
      prostatectomy and in normal human prostate epithelial and stromal cell lines.
      Western blot analysis detected a single band at 14 kDa with neurophysin antiserum
      and a 66-kDa band with oxytocin receptor antiserum in epithelial and stromal cell
      lines. Similar sized bands were also detected in extracts of hyperplastic and
      adenocarcinomic prostate tissues. Oxytocin, oxytocin-associated neurophysin and
      oxytocin receptor were present in stromal and epithelial cell lines and in tissue
      from patients with benign prostatic hyperplasia. The peptides were localised
      predominantly to the epithelial cells, although discrete areas of stromal
      staining were also observed. There was a significant difference in the intensity
      of oxytocin-staining between tissue displaying benign prostatic hyperplasia and
      invasive carcinoma, with less immunoreactivity being present in the malignant
      epithelial cells. Thus, oxytocin and its neurophysin and receptor are present in
      epithelial and stromal cells of the human prostate. Oxytocin expression is
      reduced with tumour progression and may provide a marker for invasive disease.

PMID- 15459767
TI  - Structural polarity and dynamics of male germline stem cells in the milkweed bug
      (Oncopeltus fasciatus).
AB  - The male germline stem cells (GSCs) of the milkweed bug present an extraordinary
      structural polarity that is, to our knowledge, unequalled by any other type of
      stem cells. They consist of a perikaryon and numerous projections arising from
      the cell pole directed toward the apical cells, the proposed niche of the GSCs.
      The projections can traverse a considerable distance until their terminals touch
      the apical cells. From hatching until death, the GSC projections undergo
      conspicuous changes, the sequence of which has been deduced from observations of
      all developmental stages. Projection formation starts from lobular cell
      protrusions showing trabecular ingrowths of the cell membrane. Finger-like
      projections result from a process of growth and "carving out". The newly formed
      projections contain mostly only free ribosomes other than a few mitochondria. A
      stereotyped degradation process commences in the projection terminals: profiles
      of circular, often concentric, cisternae of rough endoplasmic reticulum appear
      and turn into myelin bodies, whereas mitochondria become more numerous. The
      cytoplasm vesiculates, lysosomal bodies appear, and mitochondria become swollen.
      At the same time, the projection terminals are segregated by transverse ingrowths
      of the cell membrane. Finally, autophagic vacuoles and myelin bodies fill the
      segregated terminals, which then rupture. Simultaneously, new projections seem to
      sprout from the perikaryon of the GSCs. These dynamics, which are not
      synchronized among the GSCs, indicate that a novel type of signal exchange and
      transduction between the stem cells and their niche is involved in the regulation
      of asymmetric versus symmetric division of GSCs.

PMID- 15459768
TI  - Involvement of growth differentiation factor-15/macrophage inhibitory cytokine-1
      (GDF-15/MIC-1) in oxLDL-induced apoptosis of human macrophages in vitro and in
      arteriosclerotic lesions.
AB  - Growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1)
      is a new member of the transforming growth factor beta (TGF-beta) superfamily,
      which has most recently been found in activated macrophages (MPhi). We have now
      investigated GDF-15/MIC-1 in human MPhi after exposure to oxidized low-density
      lipoproteins (oxLDL) related mediators in vitro and in arteriosclerotic carotid
      arteries. Using RT-PCR and Western blotting a pronounced induction of GDF-15/MIC
      1 expression by oxLDL, C6-ceramide, tumor necrosis factor (TNFalpha) and hydrogen
      peroxide (H2O2) was found in cultured human MPhi. In 11 human arteriosclerotic
      carotid arteries, immunohistochemical analyses supported by computer-assisted
      morphometry and regression analyses demonstrated a significant colocalization of
      GDF-15/MIC-1 immunoreactivity (IR) with oxLDL IR and manganese superoxide
      dismutase (MnSOD) IR in CD68 immunoreactive (ir) MPhi, which were also expressing
      AIF-IR (apoptosis-inducing factor), caspase-3-IR (CPP32), PARP-IR, c-Jun/AP-1-IR
      and p53-IR. Our data suggest that GDF-15/MIC-1 is inducible in human MPhi by
      oxLDL and its mediators in vitro and is supposed to contribute to oxidative
      stress dependent consequences in arteriosclerotic plaques, e.g. modulating
      apoptosis and inflammatory processes in activated MPhi.

PMID- 15459769
TI  - Expression of e-cadherin in high-risk breast cancer.
AB  - PURPOSE: E-cadherin expression is diverse, and differences in patient
      characteristics may produce variability in expression. Whereas some studies have
      indicated that downregulation of e-cadherin, associated with loss of cellular
      adhesiveness, was correlative with poor prognosis and metastasis, other studies
      have failed to confirm this. The present study uses a highly homogenous
      population of patients at high-risk for breast cancer, on the basis of ethnic and
      socio-economic status, to examine the relationship between e-cadherin and other
      prognostic markers in breast cancer. METHODS: Immunohistochemical staining was
      undertaken for estrogen (ER) and progesterone (PR) receptors, epidermal growth
      factor receptor 2 (Her-2), p53, vascular endothelial factor (VEGF), and hypoxia
      inducible factor 1alpha (HIF-1alpha) and the levels of these markers was compared
      to e-cadherin expression in a high-risk African-American patient population.
      RESULTS: E-cadherin expression persisted into the later stagers of the disease,
      and was strongly associated with Her-2 and HIF-1alpha expression, but not p53,
      ER/PR or VEGF. CONCLUSIONS: In contrast to other studies on heterogeneous
      populations, e-cadherin is preserved in aggressive tumors in this high-risk
      population. The ethnic and socio-economic risk stratification needs to be
      accounted for in studies correlating markers and prognosis.

PMID- 15459770
TI  - Absorption, retention and tissue distribution of radiocaesium in reindeer:
      effects of diet and radiocaesium source.
AB  - Radiocaesium absorption and retention in reindeer (Rangifer tarandus) calves was
      compared in groups fed diets containing different proportions of lichen and
      concentrates, and different chemical forms of radiocaesium ((134)CsCl in solution
      or fallout from the Chernobyl accident). Daily intakes of fallout radiocaesium
      were 15-23 kBq, while daily intakes of (134)CsCl ranged from 70 kBq to 1,160 kBq.
      The half-life for radiocaesium in red blood cells (RBC) in animals fed with a
      pure lichen diet exceeded that in animals fed with a combined diet of lichen and
      concentrates by 40% (17.8+/-0.7 days vs. 12.7+/-0.4 days). Corresponding
      differences in the half-lives for urinary and faecal excretion were about 60% and
      40%, respectively. Transfer coefficients (F(f)) to reindeer meat were estimated
      to be 0.25+/-0.01 days kg(-1) for fallout radiocaesium and 1.04+/-0.03 days kg(
      1) for (134)CsCl, reflecting differences in both radiocaesium bioavailability and
      retention. The bioavailability of the Chernobyl radiocaesium in lichen in 1988
      was estimated at ca. 35% compared to (134)CsCl.

PMID- 15459771
TI  - Anti-TNF strategies in stenosing and fistulizing Crohn's disease.
AB  - BACKGROUND: Stenoses and fistulas are frequent complications in patients with
      Crohn's disease (CD). They represent a major diagnostic and therapeutic challenge
      and surgical intervention is often required. The availability of novel, anti-TNF
      strategies for therapy has raised the question as to what extent these new
      treatment options have impact on the clinical decision-making process regarding
      the necessity for surgery. DISCUSSION: A short overview of the current
      pathophysiological understanding of CD, focusing on the immunology of the
      intestinal mucosa, is given. Then the problems of proper clinical management of
      stenoses and fistulas are addressed. With regard to symptomatic stenoses,
      attention will be given to novel diagnostic tools for the distinction between
      inflammatory and fibrotic stenoses, and our clinical experience with the
      treatment of symptomatic inflammatory stenoses with infliximab will be discussed.
      With regard to fistulizing CD, the data that are currently available for medical
      therapy are summarized with special reference to the studies on the efficacy of
      anti-TNF treatment. CONCLUSION: With regard to moderately and severe inflammatory
      stenoses, medical treatment with infliximab may be an option after careful
      assessment of the inflammatory nature of the stenosis and exclusion of a septic
      focus. With regard to fistulas, anti-TNF treatment is a valuable option that is
      likely to improve the clinical outcome. Based on the available data, however,
      anti-TNF treatment cannot yet replace surgical intervention when necessary.
      Prospective trials of medical therapy and a combination of medical and surgical
      therapy for complex fistulas and internal fistulas are needed to define the
      potential and the limitations of these novel therapeutic approaches.

PMID- 15459772
TI  - Molecular detection of clinical colorectal cancer metastasis: how should multiple
      markers be put to use?
AB  - BACKGROUND AND AIMS: Up to 45% of colorectal cancer (CRC) patients will develop
      local recurrence or metastasis following curative resection. The latter is due to
      cells shed from the primary carcinoma prior to or during surgery. The aim of this
      study was to contribute toward a "rational"-approach for detecting these
      disseminated tumor cells (DTC) using a combination of independent markers and
      detection methods. PATIENTS/METHODS: Liver, lymph node, and bone marrow samples
      from 246 CRC patients were screened for DTC using three markers: mutated K-ras
      was detected by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP), and cytokeratin 20 (CK20) and guanylylcyclase C (GCC),
      indicating circulating epithelial cells, were tracked by nested reverse
      transcription (RT) PCR. RESULTS: The rate of positive findings of the individual
      markers (CK20: 88%; GCC: 88%; K-ras: 67%) and their combinations (88-50%) was
      significantly higher in biopsies from liver metastases than in liver samples from
      patients without evident distant metastasis (M0; p<0.03). The detection rate of
      individual markers (except GCC) was also significantly elevated in inconspicuous
      liver tissue adjacent to metastasis compared with specimens from M0 patients.
      When using the concomitant detection of all three markers as criterion for DTC in
      the liver of M0 patients, however, no patient was DTC-positive. Therefore, the
      concomitant presence of the two CEC markers (CK20 plus GCC) and/or the presence
      of mutated K-ras were preferred for a combined evaluation, which resulted in a
      24% detection rate for biopsies from both liver lobes. This translates into 39%
      of M0 patients with at least one positive liver biopsy. CONCLUSION: Our results
      suggest that the concomitant detection of CK20 plus GCC and/or the presence of
      mutated K-ras are a rational approach for tracking CEC/DTC in CRC patients.

PMID- 15459773
TI  - Effectiveness and tolerability of repeated treatment with infliximab in patients
      with Crohn's disease: a retrospective data analysis in Germany.
AB  - AIM: The aim was to evaluate the efficacy and safety of repeated treatment with
      infliximab in patients with chronic active Crohn's disease under routine
      conditions in clinics and private practices. METHODS: Patients with active
      Crohn's disease were treated with a total of 567 infusions (420 re-infusions) of
      infliximab. The treatment schedule was at the discretion of the treating
      physician. Efficacy and tolerability were documented by a standardized
      questionnaire. RESULTS: There were indications for therapy in 46% of patients
      with chronic active disease, fistulas in 15% and combined symptoms in 38%. The
      mean disease duration was 9.4 years. At the beginning of therapy, 76% of patients
      were on corticosteroids, 67% received 5-aminosalicylates and 48% azathioprine.
      The average dose of infliximab administered was 300 mg; the mean interval between
      individual infusions was 8.7 weeks. Following treatment with infliximab, steroids
      could be withdrawn in 47% and reduced in 33% of patients, whereas the dosage of 5
      aminosalicylates and azathioprine mostly remained unchanged. The efficacy and
      tolerability of infliximab were judged by the physicians as being very good or
      good in 73.4 and 88.4% of patients respectively. Further treatment with the anti
      TNFalpha antibody was planned for 61% of patients. Improvement of Crohn's Disease
      Activity Index (CDAI), white blood cell (WBC) and C-reactive protein (CRP) levels
      was noted in almost all patients. CONCLUSION: Infliximab used in an individually
      adapted regimen induced a significant clinical response in the majority of
      patients with refractory and fistulating Crohn's disease. In nearly 80% of
      patients corticosteroids could be withdrawn or reduced and the majority of
      patients were on azathioprine at the end of follow-up procedures.

PMID- 15459774
TI  - Laparoscopic colectomy for diverticulitis is not associated with increased
      morbidity when compared with non-diverticular disease.
AB  - BACKGROUND AND AIMS: It was the aim of this prospective study to compare the
      outcome of laparoscopic sigmoid and anterior resection for diverticulitis and non
      diverticular disease. PATIENTS AND METHODS: All patients who underwent
      laparoscopic colectomy for benign and malignant disease within a 10-year period
      were entered into the prospective PC database registry. For outcome analysis,
      patients who underwent laparoscopic sigmoid and anterior resection for
      diverticular disease were compared with patients who underwent the same operation
      for non-inflammatory (non-diverticular) disease. The parameters analyzed included
      age, gender, co-morbid conditions, diagnosis, procedure, duration of surgery,
      transfusion requirements, conversion, morbidity including major (requiring
      reoperation), minor (conservative treatment) and late-onset (postdischarge)
      complications, stay in the ICU, hospitalization, and mortality. For objective
      evaluation, only laparoscopically completed procedures were analyzed. Statistics
      included Student's t-test and chi-square analysis (p<0.05 was considered
      statistically significant). RESULTS: A total of 676 patients were evaluated
      including 363 with diverticular disease and 313 with non-inflammatory disease.
      There were no significant differences in conversion rates (6.6 vs. 7.3%, p>0.05),
      so that the laparoscopic completion rate was 93.4% (n=339) in the diverticulitis
      group and 92.7% (n=290) in the non-diverticulitis group. The two groups did not
      differ significantly in age or presence of co-morbid conditions (p>0.05). In the
      diverticulitis group, recurrent diverticulitis (58.4%), and complicated
      diverticulitis (27.7%) were the most common indications, whereas in the non
      diverticulitis group, outlet obstruction by sigmoidoceles (30.0%) and cancer
      (32.4%) were the main indications. The most common procedure was laparoscopic
      sigmoid resection, followed by sigmoid resection with rectopexy and anterior
      resection. No significant differences were documented for major complications
      (7.4 vs. 7.9%), minor complications (11.5 vs. 14.5%), late-onset complications
      (3.0 vs. 3.5), reoperation (8.6 vs. 9.3%) or mortality (0.6 vs. 0.7%) between the
      two groups (p>0.05). In the postoperative course, no differences were noted in
      terms of stay in the ICU, postoperative ileus, parenteral analgesics, oral
      feeding, and length of hospitalization (p>0.05). CONCLUSION: These data indicate
      that laparoscopic sigmoid and anterior resection can be performed with acceptable
      morbidity and mortality for both diverticular disease and non-diverticular
      disease. The results show in particular that laparoscopic resection for
      inflammation is not associated with increased morbidity.

PMID- 15459775
TI  - Radical surgery for colorectal metastatic melanoma.

PMID- 15459776
TI  - Bile infection contributes to intrahepatic calculi formation after excision of
      choledochal cysts.
AB  - Intrahepatic calculi complicate choledochal cysts in 7-8% of patients. Although
      congenital stenoses and dilatation of the intrahepatic bile ducts are considered
      responsible for calculi formation, intrahepatic calculi are usually formed after
      cyst excision. In this study, bile specimens from patients with choledochal cysts
      were cultured for bacteria. Results were retrospectively analyzed among the
      following groups: the primary excision group, consisting of 97 patients
      undergoing cyst excision as a primary treatment (mean age 5.0 years), the
      internal drainage group, consisting of 13 patients who had previous cyst
      enterostomy at cyst excision (mean age 20.2 years); and the hepatolithiasis
      group, consisting of 12 patients with postoperative hepatolithiasis (mean age
      24.2 years). Bacteria were present in the bile of 10 patients (76.9%) in the
      internal drainage group and in all patients (100%) in the hepatolithiasis group,
      but present in only 17 patients (17.5%) in the primary excision group (p<0.01).
      Polymicrobial infection with Gram-negative enterobacteria such as Escherichia
      coli and Klebsiella species was predominant in the internal drainage and
      hepatolithiasis groups, while nonenteric bacteria were found in the primary
      excision group. Bile infection through bilioenterostomy may play an important
      role in intrahepatic calculus formation after excision of a choledochal cyst.

PMID- 15459777
TI  - Connective tissue growth factor and progressive fibrosis in biliary atresia.
AB  - Connective tissue growth factor (CTGF) is a newly described protein that
      stimulates transforming growth factor-beta1 (TGF-beta1). We evaluated the
      expression of CTGF mRNA in operative biopsy specimens from biliary atresia (BA)
      patients and normal controls to assess the role of CTGF in BA. Liver biopsy
      specimens were taken from BA patients at the time of portoenterostomy (n=22) and
      compared with specimens taken from normal controls (n=6). In situ hybridization
      was used to stain CTGF mRNA in all specimens. The distribution of collagen type
      IV (C-IV) was also assessed in the same specimens as an indicator of the severity
      of fibrosis present at the time of biopsy. Results were analyzed to determine
      whether there was any correlation between CTGF and C-IV and outcome. Of the 22
      postoperative BA patients, eventual outcome was good in 17 (group I), and five
      (group II) subsequently required liver transplantation. Control specimens (n=6)
      had no apparent CTGF mRNA expression, and median C-IV positive immunoreactivity
      was 1.23+/-0.25%. CTGF mRNA was weakly expressed in hepatic stellate cells (HSC)
      and hepatocytes in specimens from group I, and median C-IV-positive
      immunoreactivity was 3.18+/-0.86%. However, in specimens from group II, there was
      increased CTGF mRNA in HSC and hepatocytes. Median C-IV-positive immunoreactivity
      was 6.31+/-0.96%. There was a significant correlation between CTGF mRNA intensity
      and the amount of C-IV, which implies that CTGF expression reflects prognosis.
      This study provides the first evidence that CTGF is strongly expressed in BA, in
      particular in HSC and hepatocytes, suggesting that they may be a source of CTGF.
      The strong correlation with C-IV indicates that CTGF plays a major role in the
      pathogenesis of progressive fibrosis in BA.

PMID- 15459778
TI  - Fetal hydrops in experimental obstructive uropathy resolves after vesicostomy
      formation: is this cause and effect?
AB  - The association of obstructive uropathy and hydrops is rare but often fatal.
      Hydrops has been observed in our fetal lamb model with obstructive uropathy. We
      created a vesicoamniotic shunt 21 days after creating the obstruction to explore
      the effect of relieving the obstruction on the hydrops. Fetal lambs underwent
      urethral and urachal ligation at 60 days gestation. We created a vesicostomy
      (female) or urethrostomy (male) in 12 lambs to release the pressure 21 days after
      creating the obstruction. The fetuses were delivered at term (145 days), and the
      urinary tract was removed for histological examination. Six fetuses had severe
      hydrops at the time of the vesicostomy (group A), and six had no hydrops (group
      B). Only two lambs from group A survived (33%), and four lambs survived from
      group B (66%). Three lambs miscarried, and one was stillborn from group A. Two
      lambs from group B miscarried. In our fetal lamb model, hydrops appears to be
      associated with massive urinary ascites. We hypothesize that a connection exists
      between urinary ascites and hydrops. Vesicostomy, by bypassing the obstruction,
      may allow the lambs to recover from their hydrops. However, it is possible that
      by 21 days after creation of the obstruction, the damage created by the hydrops
      is irreversible.

PMID- 15459779
TI  - Botryoid Wilms' tumor: a report of two cases.
AB  - We report two rare cases of botryoid Wilms' tumor (BWT) occupying the renal
      collecting system with no macroscopic parenchymal mass. In case 1, a 3-year-old
      boy presented with a mass in the right flank, low-grade fever, abdominal pain,
      and macrohematuria. Radiology revealed an enlarged right kidney with a
      heterogeneous mass occupying a large part of the dilated renal calyx, pelvis, and
      ureter. Radical right nephroureterectomy was performed. The histopathologic
      diagnosis was nephroblastoma, and the pedicle of the tumor was attached to the
      renal parenchyma near the pelvic wall. In case 2, a 2-year-old boy presented with
      macrohematuria, and the clinical course was almost the same as in case 1. No
      local recurrence or metastatic spread has been detected for 4 years
      postoperatively in case 1 and for 9 months postoperatively in case 2.

PMID- 15459780
TI  - Blunt liver trauma in children.
AB  - Diagnostic evaluation and treatment of blunt liver trauma in children have
      changed essentially over the last decades. In the period between January 1975 and
      December 2002, a total of 45 children, 18 girls and 27 boys, between the ages of
      1 and 16 years (mean 8.19) were treated for liver rupture following blunt
      abdominal trauma. The most common causes of injury were traffic accidents (49%),
      followed by falls (22%), direct trauma due to impact (20%) and being run over by
      a vehicle (9%). A total of 26 patients had one or more concomitant injuries; the
      injury severity score was between 16 and 57 (mean 22.9), and 16 patients had
      additional injuries to other solid abdominal organs. Since we last used
      laparotomies to explore the abdomen and manage liver ruptures in 1984, we divided
      our patients into two groups with respect to the choice of diagnostic and
      treatment modalities: group I, consisting of children treated before 1984, and
      group II, consisting of children treated after 1985. In group I (n=12), a
      diagnosis was made in eight cases based on exploratory laparotomy, in two cases
      based on sonography and laparoscopy, in one case based on laparoscopy only, and
      in another case based on sonography only. In eight cases the rupture was treated
      operatively; there was one postsurgical sepsis and one ileus due to adhesions.
      One child hemorrhaged to death when the vena cava ruptured during surgery. In
      group II (n=33), sonography was sufficient for a diagnosis in 18 cases. In 12
      cases an additional computed tomographic scan was performed following initial
      sonography, and in three cases a diagnostic laparotomy was done elsewhere. In
      five cases the rupture was treated operatively in other hospitals. Twenty-eight
      patients could be treated conservatively and without any complications. One child
      died 3 days after the accident as a result of a severe brain injury. Over the
      past 15 years we have seen a clear tendency toward conservative treatment of our
      patients, which is also in agreement with current literature. Initial sonography,
      supplemented by computed tomography when necessary, allows not only noninvasive
      initial diagnostic evaluation but is also helpful in the further course in
      hemodynamic stable patients. All patients who had been treated conservatively
      (n=30) had no complications related to the liver rupture.

PMID- 15459781
TI  - Prenatal bilateral extravaginal testicular torsion--a case presentation.
AB  - A newborn male presented at birth with findings consistent with bilateral
      testicular torsion. Preoperative ultrasound demonstrated no flow to either
      testicle, and he underwent surgery, during which bilateral extravaginal
      testicular torsion was confirmed. The right testicle was grossly necrotic and
      orchidectomy was performed, whereas the left testicle was indeterminate and
      underwent detorsion and orchidopexy. At 6-month follow-up, the left testicle
      remained within normal clinical limits with good flow on ultrasound examination.

PMID- 15459782
TI  - Ovarian fibroma in a 7-month-old infant: a case report and review of the
      literature.
AB  - Ovarian fibroma rarely occurs in prepubertal girls. We report an ovarian fibroma
      in a 7-month-old female infant presenting as a right abdominal mass. The tumour
      was composed of oval-to-spindle cells forming interlacing fascicles and
      intermingling with collagen fibres. Immunohistochemically, the tumour cells were
      weakly positive for estrogen receptor and progesterone receptor but negative for
      inhibin. To the best of our knowledge, this is the youngest case of ovarian
      fibroma up-to-date in the English literature. Because Gorlin's syndrome was not
      present in the patient's family, other factors such as germline or somatic
      mutations may predispose the occurrence of this ovarian fibroma in infancy.

PMID- 15459783
TI  - Association of a fetal quadrigeminal cyst with a possibly congenital thalamic
      astrocytoma.
AB  - CASE REPORT: This article reports on the exceptional association of a fetal
      quadrigeminal malformative cyst with a possibly congenital pilocytic astrocytoma
      of the pulvinar. Both the cyst and the tumor required treatment due to their
      postnatal growth. DISCUSSION: Treatment modalities and difficulties are
      emphasized, as well as the difficulties of prenatal counseling.

PMID- 15459784
TI  - Transumbilical approach for shunt insertion in the pediatric population: an
      improvement in cosmetic results.
AB  - OBJECTIVE: In spite of the recent interest in endoscopic third ventriculostomy,
      ventriculoperitoneal (VP) shunt is still the gold standard in treating non
      obstructive hydrocephalus in children. The peritoneal cavity remains the optimal
      site for cerebrospinal fluid (CSF) diversion. Shunt insertion and re
      interventions carry a high risk of inaesthetic abdominal scars and long-term
      morbidity. We report a technique of transumbilical shunt insertion, which
      provides better cosmetic results and without many more complications. This
      approach has been performed for a long period in a wide variety of intra
      abdominal conditions by pediatric surgeons. METHODS: Between March and October
      2003, we inserted 12 VP shunts in children. For eight consecutively treated
      children the follow-up is more than 3 months. All the shunts were inserted
      through the umbilicus. These eight children are the subjects of this study.
      Indications for shunting were: communicating hydrocephalus (6 cases), subdural
      hematoma (1 case), and hygroma associated with an arachnoid cyst (1 case). The
      population consisted of 7 boys and 1 girl, ranging in age between 6 weeks and 47
      months (mean age: 15 months), and their body weights varied between 2,110 g and
      18,000 g (mean weight: 8,470 g). All children were examined twice a day for 3
      days, and wounds were examined daily to check for the absence of sepsis or
      dehiscence. Clinical controls were performed 1 month after discharge. The
      operating surgeon was invited to comment on any difficulties encountered in
      making or closing this incision afterwards. RESULTS: The average length of
      clinical follow-up was 6 months (range 4-7 months). One infection of the VP shunt
      occurred. It was treated with external drainage and antibiotics. After 1 week, a
      second VP shunt was inserted using the same technique without particular
      difficulty and with a nice cosmetic result. Concerning the seven other children,
      the cosmetic results were optimal, with no puckered abdominal scars or wound
      dehiscence, and with no perioperative or long-term complications related to the
      umbilical approach. CONCLUSION: At this early follow-up, umbilical incision for
      shunt insertion is a safe and easy technique. It provides an optimal cosmetic
      result, even in cases of re-intervention. This minimally invasive surgery does
      not require long specialized training. We have not shown an increase in
      complications associated with a "learning curve." Longer follow-up is needed to
      evaluate the risk of infection.

PMID- 15459785
TI  - Spinal tuberculosis: with reference to the children of northern India.
AB  - BACKGROUND: Tuberculosis is a necrotizing bacterial infection with protean
      manifestation and wide distribution. There has been a great fall in the
      prevalence of tuberculosis in the United States since 1990, although the impact
      of acquired immunodeficiency syndrome (AIDS) has increased the resurgence of
      tuberculosis (TB). Spinal tuberculosis is the commonest form of skeletal
      tuberculosis. In this article, an overview of spinal tuberculosis and the
      personal experience of 19 children with spinal tuberculosis are presented. All
      the children required surgical intervention, because they manifested neurological
      deficit. PATHOGENESIS AND CLINICAL FEATURES: The spinal tuberculosis is a result
      of hematogenous dissemination from primary focus in the lungs or the lymph nodes.
      The central type of vertebral tuberculosis spreads along with Batson's plexus of
      veins, while paradiscal infection spreads through the arteries. The anterior type
      of vertebral body tuberculosis results from the extension of the abscess beneath
      the anterior longitudinal ligament and periosteum. Two types of bone and joint
      tuberculosis are recognized: the caseous, exudative type with abscess formation,
      which is more common in children, and the granular type is frequent in adults.
      Only 7 of the 19 children had an abscess, while 10 manifested mainly granulation
      tissue. Although spinal tuberculosis is an extradural disease, 2 children had
      intramedullary granulomas and presented a tumor-like syndrome as rare
      manifestations. It was interesting to encounter intradural granulation and
      organized intradural granuloma causing cord compression in 2 children. A frank
      abscess with clumping of nerve roots was encountered in the cauda of another
      child without vertebral involvement. There is a controversy regarding the age
      predilection of the disease; it is documented that it is a disease of adults in
      affluent countries, and a disease of the first three decades in other regions.
      DIAGNOSIS: Magnetic resonance imaging is extremely useful in diagnosing the
      difficult and rare sites of disease like the craniovertebral junction. It detects
      the marrow changes, exudative and granulation types, extra- and intradural
      disease, and radiological response to treatment in the early follow-up period
      around 6-8 weeks. TREATMENT: Opinion varies regarding the operative indication
      for Pott's spine. A large group of surgeons perform debridement and decompression
      in all cases, irrespective of neurological involvement. Others perform operative
      decompression only in those patients who do not respond to chemotherapy. We did
      surgical interventions in children with moderate to severe neurological deficits
      manifesting radiological compression of their neuraxis. Depending on the site of
      involvement and type of disease the surgical approach was decided in individual
      cases. Two children with healed Pott's spine also required surgery because of
      their spinal deformations, which caused gradual neurological deficits and pain in
      both. Prognosis depends on many factors; the magnitude of cord compression,
      duration of neural complication, age and general condition of patient. Fifteen of
      our children made a remarkable recovery. Children with paraplegia also made an
      excellent recovery of their strength and sensations.

PMID- 15459786
TI  - [Optical coherence tomography].

PMID- 15459787
TI  - [Optical coherence tomography for macular edema. Classification, quantitative
      assessment, and rational usage in the clinical practice].
AB  - Optical coherence tomography (OCT) allows for morphological assessment of macular
      edema of various origins by producing two-dimensional images of the retina. In
      addition, retinal thickness can be measured quantitatively. In diabetic
      maculopathy, damage of the blood-retinal barrier can be indirectly assessed by
      locating the intraretinal fluid accumulation and the progress of maculopathy from
      diffuse to cystoid edema and even rupture of the retinal structure can be
      described as well as the formation of neurosensory retinal detachment with
      subretinal fluid. Increase of retinal thickness correlates with decrease in
      visual acuity. Detailed interpretation of OCT images can replace fluorescein
      angiography in certain cases, as has been shown for uveitis. In order to obtain
      correct classification of macular disease in routine clinical use, all images
      have to be completely assessed and compared to previous investigations and to the
      measurements of the fellow eye. More accurate normal values of retinal thickness
      and volume can be expected in the future. The importance of OCT in routine
      clinical assessment of macular edema will most probably continue to grow.

PMID- 15459788
TI  - [OCT in age-related macular degeneration. Findings, usage in clinical routine,
      and assessment of treatment outcome].
AB  - Optical coherence tomography (OCT) represents a fast and noninvasive examination
      technique that generates two-dimensional sections of the posterior pole in vivo.
      Although this method is now widely applied in the diagnosis of various
      heterogeneous macular diseases, its role in patients with age-related macular
      degeneration (AMD) is less well established. OCT allows for quantitative as well
      as qualitative assessment of various AMD phenotypes. Qualitative assessment
      comprises the evaluation of intra- or subretinal fluid, intraretinal cystoid
      spaces, and retinal pigment epithelial detachments. However, together with the
      clinical findings and fluorescence angiography, it can provide useful additional
      information including monitoring of treatment effects.

PMID- 15459789
TI  - [Methodological advancements. Ultrahigh-resolution OCT].
AB  - Development of ultrabroad bandwidth light sources has recently enabled
      significant improvement of ophthalmic axial OCT imaging resolution, demonstrating
      the potential of ultrahigh resolution OCT (UHR OCT) to perform noninvasive
      optical biopsy, i.e., the in vivo visualization of microstructural morphology in
      situ, which had previously only been possible with histopathology. Therefore, UHR
      OCT allows detection of intraretinal changes that can be used for diagnosis of
      retinal disease in its early stages when treatment is most effective and
      irreversible damage can be prevented or delayed. Furthermore, it may provide a
      better understanding of the pathogenesis of several macular pathologies as well
      as contribute to the development of new therapy approaches. Future developments
      of ophthalmic OCT include high speed, three-dimensional retinal imaging,
      combining adaptive optics and UHR OCT, spatially resolved spectroscopic OCT,
      functional imaging, and OCT imaging with enhanced penetration into the choroid by
      employing novel wavelength regions.

PMID- 15459791
TI  - [Cycling with a visual handicap].
AB  - PURPOSE OF THE STUDY: To examine bicycling habits of visually handicapped people
      in order to learn about the visual requirements. MATERIAL AND METHODS: Survey of
      patients (age range: 14-60 years) suffering from macular or tapetoretinal
      degeneration with no additional relevant handicap using a questionnaire. RESULTS:
      A total of 232 questionnaires were returned (62% of the questionnaires received
      by the participants). The results showed that if visual acuity dropped below 0.1,
      only 15% of the patients were able to ride a bicycle without accidents or near
      accidents. This percentage increased for higher acuities between 33% (<0.2 > or =
      0.1) and 67% (> or = 0.2 < or = 0.4). For visual field diameters <60 degrees and
      > or = 20 degrees approximately 18% were able to ride a bicycle safely and only
      8% if the visual field diameter was below 20 degrees. For visual fields larger
      than 60 degrees diameter approximately 40% were able to ride a bicycle without
      problems. With a central scotoma of more than 10 degrees diameter only 21% of the
      patients could cycle safely, whereas with a central scotoma of 10 degrees and
      less this percentage increased to 47%. CONCLUSIONS: A visual acuity of less than
      0.1 is not sufficient to ride a bicycle, and a visual acuity of less than 0.2
      leads to a higher accident rate. A visual field diameter of less than 60 degrees
      or a central scotoma of more than 10 degrees diameter for the vast majority of
      patients does not allow safe cycling

PMID- 15459792
TI  - [Molecular genetic findings in patients with congenital cone dysfunction.
      Mutations in the CNGA3, CNGB3, or GNAT2 genes].
AB  - PURPOSE: This study compares clinical and molecular genetic findings in patients
      with congenital cone dysfunction. METHODS: In this study 28 patients underwent a
      basic ophthalmologic examination. Except for a 1-year-old boy, color vision,
      perimetry, and full-field ERG (ISCEV standard) were evaluated in all patients.
      Blood samples were taken for molecular genetic analysis of the CNGA3, CNGB3, or
      GNAT2 genes. RESULTS: Two patient groups could be distinguished: patients without
      and with residual cone function in the ERG. In 14 of 17 patients without cone
      function, mutations in one of the three genes were detected, and except for one
      patient mutations in both alleles could be determined. In these patients, visual
      acuity was reduced to 20/400 and color discrimination was absent. In 2 of 11
      patients with residual cone function, mutations in one allele of the CNGB3 gene
      were detected. It is of interest that 6 of 16 patients with mutations perceived
      their disease as progressive; in three of them we could determine a progression.
      Only in 4 of 16 patients was the ocular fundus normal. The other patients with
      mutations presented with central pigment irregularities, attenuated vessels, or
      pale optic disk. CONCLUSION: In patients with congenital cone dysfunction without
      cone function in the ERG, an analysis of the CNGA3, CNGB3, or GNAT2 gene is
      advisable. In contrast, patients with residual cone function did not show clear
      association with mutations in one of the three genes. In patients with mutations,
      retinal alterations and nystagmus are frequent. In contrast to the designation of
      these disorders as stationary, in some patients with mutations in the CNGA3 and
      CNGB3 gene slow progression was observed.

PMID- 15459793
TI  - [Central pigment epithelial defect in a 33 year-old female patient. A 33 year-old
      female patient with neurological symptoms, central pigment epithelial defect and
      limited upward gaze].

PMID- 15459794
TI  - [Presence of TINU syndrome in a case of unresolved "idiopathic" uveitis].

PMID- 15459795
TI  - Estimating the copy number of transgenes in transformed rice by real-time
      quantitative PCR.
AB  - In transgenic plants, transgene copy number can greatly influence the expression
      level and genetic stability of the target gene, making estimation of transgene
      copy number an important area of genetically modified (GM) crop research.
      Transgene copy numbers are currently estimated by Southern analysis, which is
      laborious and time-consuming, requires relatively large amounts of plant
      materials and may involve hazardous radioisotopes. We report here the development
      of a sensitive, high-throughput real-time (RT)-PCR technique for estimating
      transgene copy number in GM rice. This system uses TaqMan quantitative RT-PCR and
      comparison to a novel rice endogenous reference gene coding for sucrose phosphate
      synthase (SPS) to determine the copy numbers of the exogenous beta-glucuronidase
      (GUS) and hygromycin phosphotransferase (HPT) genes in transgenic rice. The copy
      numbers of the GUS and HPT in primary rice transformants (T0) were calculated by
      comparing quantitative PCR results of the GUS and HPT genes with those of the
      internal standard, SPS. With optimized PCR conditions, we achieved significantly
      accurate estimates of one, two, three and four transgene copies in the T0
      transformants. Furthermore, our copy number estimations of both the GUS reporter
      gene and the HPT selective marker gene showed that rearrangements of the T-DNA
      occurred more frequently than is generally believed in transgenic rice.

PMID- 15459798
TI  - Applications of biopolymers and other biotechnological products in building
      materials.
AB  - Bio admixtures are functional molecules used in building products to optimize
      material properties. They include natural or modified biopolymers,
      biotechnological and biodegradable products. Concrete and dry-mix mortars (e.g.
      wall plasters or tile adhesives) represent two major applications for bio
      admixtures. Examples of bio products used in concrete are lignosulfonate, sodium
      gluconate, pine root extract, protein hydrolysates and Welan gum; and in dry-mix
      mortar methyl hydroxypropyl cellulose, hydroxypropyl starch, guar gum, tartaric
      acid, casein, succinoglycan and Xanthan gum. In a number of applications, bio
      admixtures compete well with synthetic admixtures. Sometimes, they are
      indispensable in the formulation of certain building products. Their market share
      is expected to increase because of technological advances, particularly in the
      field of microbial biopolymers, and because of the growing trend to use naturally
      based or biodegradable products in building materials.

PMID- 15459796
TI  - The transcriptional program of synchronous gametogenesis in Chlamydomonas
      reinhardtii.
AB  - Cells of Chlamydomonas reinhardtii undergo gametogenesis to produce sexually
      competent gametes under nitrogen-starved conditions. By using a synchronized
      system for gametogenesis of early G1 cells, several previously identified marker
      genes and 18 novel nitrogen-starved gametogenesis (NSG) genes isolated by
      macroarray analysis were placed into at least three temporal classes of
      expression. Early genes are induced transiently in the first 2 h after transfer
      to nitrogen-free medium. Middle genes are strongly induced between 3 h and 4 h
      after nitrogen removal, a time corresponding to the acquisition of mating
      competency, suggesting their involvement in the gamete program. Late genes are
      induced between 5 h and 8 h after nitrogen removal, a time after the completion
      of gametic differentiation, suggesting that they are not directly involved in the
      formation of sexually competent gametes. All of the 18 NSG genes examined are
      induced in both mating-type plus and minus gametes and about two-thirds of the
      genes are also expressed in the mitotic cell cycle, especially at S/M phases.

PMID- 15459799
TI  - Batch and fed-batch production of coenzyme Q10 in recombinant Escherichia coli
      containing the decaprenyl diphosphate synthase gene from Gluconobacter
      suboxydans.
AB  - Coenzyme Q(10) (CoQ(10)) is a quinine consisting of ten units of the isoprenoid
      side-chain. Because it limits the oxidative attack of free radicals to DNA and
      lipids, CoQ(10) has been used as an antioxidant for foods, cosmetics and
      pharmaceuticals. Decaprenyl diphosphate synthase (DPS) is the key enzyme for
      synthesis of the decaprenyl tail in CoQ(10) with isopentenyl diphosphate. The
      ddsA gene coding for DPS from Gluconobacter suboxydans was expressed under the
      control of an Escherichia coli constitutive promoter. Analysis of the cell
      extract in recombinant E. coli BL21/pACDdsA by high performance liquid
      chromatography and mass spectrometry showed that CoQ(10) rather than endogenous
      CoQ(8) was biologically synthesized as the major coenzyme Q. Expression of the
      ddsA gene with low copy number led to the accumulation of CoQ(10) to 0.97 mg l(
      1) in batch fermentation. A high cell density (103 g l(-1)) in fed-batch
      fermentation of E. coli BL21/pACDdsA increased the CoQ(10) concentration to 25.5
      mg l (-1) and its productivity to 0.67 mg l(-1) h(-1), which were 26.0 and 6.9
      times higher than the corresponding values for batch fermentation.

PMID- 15459800
TI  - Neuron-transistor coupling: interpretation of individual extracellular recorded
      signals.
AB  - The electrical coupling of randomly migrating neurons from rat explant brain-stem
      slice cultures to the gates of non-metallized field-effect transistors (FETs) has
      been investigated. The objective of our work is the precise interpretation of
      extracellular recorded signal shapes in comparison to the usual patch-clamp
      protocols to evaluate the possible use of the extracellular recording technique
      in electrophysiology. The neurons from our explant cultures exhibited strong
      voltage-gated potassium currents through the plasma membrane. With an improved
      noise level of the FET set-up, it was possible to record individual extracellular
      responses without any signal averaging. Cells were attached by patch-clamp
      pipettes in voltage-clamp mode and stimulated by voltage step pulses. The point
      contact model, which is the basic model used to describe electrical contact
      between cell and transistor, has been implemented in the electrical simulation
      program PSpice. Voltage and current recordings and compensation values from the
      patch-clamp measurement have been used as input data for the simulation circuit.
      Extracellular responses were identified as composed of capacitive current and
      active potassium current inputs into the adhesion region between the cell and
      transistor gate. We evaluated the extracellular signal shapes by comparing the
      capacitive and the slower potassium signal amplitudes. Differences in amplitudes
      were found, which were interpreted in previous work as enhanced conductance of
      the attached membrane compared to the average value of the cellular membrane. Our
      results suggest rather that additional effects like electrodiffusion, ion
      sensitivity of the sensors or more detailed electronic models for the small cleft
      between the cell and transistor should be included in the coupling model.

PMID- 15459801
TI  - Raman piezo-spectroscopic analysis of natural and synthetic biomaterials.
AB  - Raman piezo-spectroscopy of bone, teeth, and artificial joints is reviewed with
      emphasis placed on confocal microprobe techniques. Characteristic spectra are
      presented and quantitative assessments of their phase structure and stress
      dependence are shown. Vibrational spectroscopy is used here to study the
      microscopic stress response of cortical bone to external stress (with or without
      internal damages), to define microscopic stresses across the dentine-enamel
      junction under increasing external compressive load, and to characterize
      interactions between prosthetic implants and biological environment. Confocal
      spectroscopy allows acquisition of spatially resolved spectra and stress imaging
      with high spatial resolution.

PMID- 15459802
TI  - Determination of serum cortisol using isotope dilution-liquid chromatography-mass
      spectrometry as a candidate reference method.
AB  - We propose isotope-dilution mass spectrometry as a candidate reference method for
      determination of serum cortisol. The method uses liquid chromatography-mass
      spectrometry (LC-MS), interfaced with electrospray ionization, and selective
      monitoring of the [M + H]+ ions of cortisol and isotopically labeled cortisol.
      The isotope-dilution-liquid chromatography-mass spectrometry (ID-LC-MS) method
      simplifies sample-preparation, because samples are processed by simple solvent
      extraction without further clean-up and derivatization. We studied the time
      required for complete equilibration of endogenous cortisol and labeled cortisol
      spiked into serum and found it to be less than 1 h. The repeatability and the
      reproducibility of the method were evaluated and found to be 0.55% of the
      measurement value. CRM 192 and 193 from the Bureau Communautaire de Reference
      were analyzed for verification of the method. The results obtained from the ID-LC
      MS method agreed with the certified values. The relative uncertainty of
      measurement results for samples in the range of a few tens of micrograms per
      kilogram to several hundred micrograms per kilogram was evaluated and found to be
      0.56%. Immunoassay carried out by three independent clinical laboratories
      produced results more than 15% higher than this ID-LC-MS method, suggesting the
      presence of bias in the immunoassay methods.

PMID- 15459803
TI  - Inhibition of protein kinase C-mediated contraction by Rho kinase inhibitor
      fasudil in rabbit aorta.
AB  - Protein kinase C (PKC) activation by a phorbol ester increases myosin light chain
      (MLC(20)) phosphorylation through inhibition of MLC phosphatase (MLCP) and
      enhances contraction of vascular smooth muscle. We investigated whether Rho
      kinase, which is known to inhibit MLCP, is involved in the MLC(20)
      phosphorylation caused by a phorbol ester, 12-deoxyphorbol 13-isobutyrate (DPB),
      in rabbit aortas. DPB (1 microM) increased MLC(20) phosphorylation and tension.
      The Rho kinase inhibitor fasudil (10 microM) inhibited the DPB-induced
      contraction and decreased the MLC(20) phosphorylation at Ser19, a site
      phosphorylated by MLC kinase, although it did not affect the phosphorylation of
      total MLC(20). Rinsing a 65.4 mM KCl-contracted aorta with Ca(2+)-free, EGTA
      solution caused rapid dephosphorylation of MLC(20) and relaxation. When DPB was
      present in the rinsing solution, the MLC(20) dephosphorylation and the relaxation
      were inhibited. In this protocol, Ro31-8220 (10 microM), a PKC inhibitor,
      suppressed the phosphorylation of total MLC(20) and Ser19 induced by DPB. Fasudil
      also inhibited the Ser19 phosphorylation to a degree similar to Ro31-8220 and
      accelerated relaxation, which was less than the relaxation caused by Ro31-8220.
      The phospholipase A(2) inhibitor ONO-RS-082 (5 microM) inhibited the DPB-induced
      Ser19 phosphorylation but only transiently decreased the tension, suggesting the
      involvement of arachidonic acid in the phosphorylation and the existence of a
      MLC(20) phosphorylation-independent mechanism. When fasudil was combined with ONO
      RS-082, fasudil exerted additional inhibition of the tension without further
      inhibition of the Ser19 phosphorylation. DPB phosphorylated the 130 kDa myosin
      binding subunit (MBS) of MLCP and fasudil inhibited the phosphorylation. These
      data suggest that the inhibition by fasudil of DPB-induced contraction and
      phosphorylation of MLC(20) at the MLC kinase-targeted site is a result of
      inhibition of Rho kinase. Thus, the PKC-dependent Ca(2+)-sensitization of
      vascular smooth muscle involves Rho kinase. A MLC(20) phosphorylation-independent
      mechanism is also involved in the Ca(2+)-sensitization.

PMID- 15459804
TI  - Bone ultrasonography in glucocorticoid-induced osteoporosis.
AB  - Osteoporosis is one of the major complications of glucocorticoid (GC) therapy.
      Few data are available on the usefulness of quantitative ultrasound (QUS), a
      technique that could also theoretically provide information on bone structure, in
      the management of glucocorticoid-induced osteoporosis (GIO). This study aimed (1)
      to evaluate the ability of QUS in detecting bone impairment and in being
      associated with the prevalence of fragility fracture in GC patients; and (2) to
      assess whether QUS parameters, and particularly the graphic trace analysis of QUS
      signal at phalanges, show any peculiar pattern of GIO. We studied 192 patients
      (136 women and 56 men, mean age 56.7 +/- 14.2 years) on treatment with GCs for at
      least 6 months, and 192 sex- and age-matched controls. In all subjects, we
      measured bone mineral density (BMD) at lumbar spine and at femur by DXA, and
      ultrasound parameters at calcaneus and phalanges. All DXA and QUS parameters were
      significantly lower in GC patients than in controls and in fracture than in
      nonfracture GC patients. BMD at lumbar spine showed the best ability in
      discriminating GC patients with or without fractures. Among QUS parameters,
      stiffness showed a discriminatory ability significantly better than AD-SoS. BMD
      at lumbar spine and total femur, stiffness, and AD-SoS are able to predict the
      odds of fragility fracture event. QUS parameters of the postmenopausal GC
      patients (n = 105) and of the postmenopausal healthy controls (n = 101) were also
      compared with those obtained in a separate sample of 90 postmenopausal
      osteoporotic women (PMO). All parameters were significantly lower in GC patients
      and in PMO than in controls, without any significant difference between GC and
      PMO. Our findings show that QUS can be useful in the assessment of glucocorticoid
      induced bone impairment. In addition, in this study we found no alteration in QUS
      parameters or in the graphic trace analysis which could differentiate between GIO
      and PMO. Further longitudinal studies are needed to define the role of QUS in the
      prediction of fracture risk and in the clinical management of GIO.

PMID- 15459805
TI  - [Personnel and structural requirements for the shock trauma room management of
      multiple trauma. A systematic review of the literature].
AB  - The aim of the study was the description of personal and structural preconditions
      essential for adequate diagnostic requirements and treatment in severely injured
      patients. Herein we give detailed information regarding both the composition and
      qualification of the trauma team and the activation criteria as well as
      instructions for the design of the emergency room and technical requirements.
      Clinical trials were systematically collected (MEDLINE, Cochrane, and hand
      searches) and classified into evidence levels (1 to 5 according to the Oxford
      system). The trauma team should consist of (trauma) surgeons, anesthesiologists,
      radiologists, and one to two nursing staff members of each department. The
      attending physician should be present within 20 min. Trauma team activation
      criteria are among others: high energy/velocity trauma, penetrating injuries, GCS
      < or =14, and intubation. The emergency room should be integrated in the
      emergency department with all technical equipment being permanently available for
      optimal diagnostic and therapeutic management. A CT scanner should be positioned
      nearby.Adequate management of severely injured patients requires optimal personal
      and structural conditions. High costs and additional personnel are justified by
      improved quality of treatment.

PMID- 15459806
TI  - [Shock trauma room management of spinal injuries in the framework of multiple
      trauma. A systematic review of the literature].
AB  - Injuries to the spine are often part of life-threatening multiple trauma. In this
      review diagnostics and emergency room management were investigated in order to
      formulate effective recommendations for the emergency strategy. Clinical trials
      were systematically collected (MEDLINE, Cochrane, and hand searches) and
      classified into evidence levels (1 to 5 according to the Oxford system). The
      patient's history and clinical symptoms have low rates for specificity and
      positive predictive value, whereas their negative predictive value and
      sensitivity are high between 90 and 100%, respectively. CT imaging reaches higher
      rates for sensitivity, specificity, and positive and negative predictive values
      in comparison to conventional radiographic series. The patient's history should
      be asked and clinical investigation should be done in any case. Imaging
      diagnostics preferably as multislice spiral CT should be performed after
      stabilization of the patient's general condition and before admission to the
      intensive care unit.

PMID- 15459807
TI  - [An open wedge tibial head osteotomy using continuous callus distraction. An
      alternative method for the treatment of of varus arthrosis].
AB  - High tibial osteotomy is an accepted method for treatment of medial
      osteoarthritis. An alternative technique is an open-wedge osteotomy and
      consecutive callotasis (CO) using an external fixator. The purpose of this study
      was to evaluate the clinical and radiological results and the efficiency of this
      technique for precise correction. This prospective study included 41 patients (44
      knees) evaluated by the HSS score, radiological stage of osteoarthritis, bone
      healing, and complications after a follow-up period of 49 (36-61) months. The HSS
      score increased from median 67 preoperatively to 82 points at the time of follow
      up (p<0.001). Of 44 knees, excellent/good results were found in 70.5% and
      fair/poor in 29.5%. The median preoperative femorotibial anatomical angle was 3.6
      degrees varus and 9.4 degrees valgus at the latest follow-up examination. The
      total time in external fixation was median 80 (61-125) days. We observed one
      early collapse of the new bone wedge, one complete corticotomy, and pin tract
      infections in ten cases. Furthermore, two hematomas required revision surgery.
      Hemicallotasis with external fixators allows constant manipulation of alignment
      during the healing process to optimize alignment. The disadvantage of the
      external fixation is the risk of pin track infection. Therefore, CO may
      constitute an important contribution to our algorithm in the treatment of varus
      gonarthrosis.

PMID- 15459808
TI  - [Diagnosis and immediate therapeutic management of chest trauma. A systematic
      review of the literature].
AB  - OBJECTIVE: Injuries to the chest contribute significantly to the morbidity and
      mortality in multiple injured patients. This systematic review focuses on
      evidence based initial diagnostics and emergency room management of chest trauma.
      METHODS: Clinical trials was systematically collected (Medline, Cochrane and hand
      searches) and classified into evidence levels (1 to 5 according to the Oxford
      system). RESULTS: There are only a few studies that document the impact of injury
      mechanism and clinical examination of the patient. There is a positive
      correlation between crash severity or lateral impact with injury severity.
      Auscultation was found to be very sensitive in the detection of pneumothorax.
      Helical CT of the chest is most important in the initial work-up. Aortography is
      only indicated in selected cases. Whether tube thoracostomy is necessary in
      patients with occult pneumotharaces is still a matter of discussion. Indications
      for endotracheal intubation are poorly investigated and predominantly based on
      expert opinion. CONCLUSION: Numerous comparative studies (LE 2) dealing with
      emergency diagnostics and therapy of chest trauma are available, however only a
      few randomized studies do exist. Based on the available data a rational therapy
      of chest trauma is possible.

PMID- 15459809
TI  - [Post-traumatic torsional differences and functional tests following antegrade or
      retrograde intramedullary nailing of the distal femoral diaphysis].
AB  - Previous studies have compared the functional outcome and torsional differences
      following closed intramedullary nailing of femoral fractures. Rotational
      deformity following intramedullary nailing may cause symptoms and require
      surgical correction by osteotomy. Until now studies were designed to evaluate the
      correct torsional differences by examining every patient following antegrade or
      retrograde femoral nailing. The series included 13 women and 28 men, average age
      44.5 years, who suffered a fracture of the distal femoral diaphysis.
      Postoperatively we established the diagnosis by three-dimensional determination
      of the torsion and length of the lower extremities by ultrasound measurement.
      Furthermore, we performed the clinical examination according to the Tegner and
      Lysholm score and the Merle d'Aubigne score. There were no significant
      differences in torsional deformity and length found. The functional outcome
      showed no significant differences between the two groups. The functional
      examination exhibited a reduction of flexion in knee motion in the retrograde
      group. In the antegrade group the motion of the hip was decreased. A correlation
      between the functional outcome and the torsional deformity was not found. The
      possible advantage of positioning by using the retrograde femoral nail was not
      verified.

PMID- 15459810
TI  - [Shock trauma room diagnosis: initial diagnosis after blunt abdominal trauma. A
      review of the literature].
AB  - OBJECTIVE: Blunt abdominal trauma is most common in the polytraumatized patient
      and beside neurocranial trauma one major determinant of early death in these
      patients. Therefore, immediate recognition of an abdominal injury is of life
      saving importance. METHODS: Clinical trials were systematically collected
      (Medline, Cochrane and hand searches) and classified into evidence levels (1 to 5
      according to the Oxford system). RESULTS: Clinical examination is not reliable
      for evaluation of abdominal injury. Abdominal ultrasound, especially if only
      focusing on free fluid (FAST) is not sensitive enough. Today, CT-scan of the
      abdomen is the gold-standard in diagnosing abdominal injury. Diagnostic
      Peritoneal Lavage (DPL) has a high sensitivity but in our region only is used in
      exceptional cases. The patient with continuing hemodynamical instability after
      abdominal trauma and evidence of free intraperitonial fluid has to undergo
      laparotomy. CONCLUSION: After blunt abdominal trauma, initially ultrasound
      investigation should be performed in the emergency room. This should not only
      focus on free intraabdominal fluid but also on organ lesions. Regardless of the
      findings from ultrasound or clinical examination, the hemodynamically stable
      patient should undergo a CT-scan of the abdomen in order to proof or exclude an
      abdominal injury.

PMID- 15459811
TI  - Atlanto-odontoid osteoarthritis in rheumatoid arthritis: dynamic CT findings.
AB  - We analyzed the CT appearances of degenerative change in the atlanto-odontoid
      joint (AOJ) in patients with rheumatoid arthritis (RA) and evaluated the effect
      of these changes on atlanto-axial joint (AAJ) rotation by dynamic CT. This
      revealed that 9 patients (24%) treated with methotrexate had degenerative
      features in the AOJ. The ratio of AAJ rotation to the total rotation of the
      cervical spine was significantly higher in normal subjects (54 +/- 3%) than in
      patients (38 +/- 12%). The degree of AAJ rotation was significantly lower in the
      patient group with degenerative features in the AOJ (20.9 +/- 8.4 degrees ) than
      in patients without degenerative features (28.5 +/- 7.4 degrees ). RA patients
      with a history of longstanding disease and treatment with antirheumatic drugs may
      develop AO OA. Although secondary OA was described as healing phenomena in the
      joints of RA patients, it can limit rotation in the AAJ and cause suboccipital
      neck pain. A regular check-up of the AAJ and AOJ by means of dynamic CT in all RA
      patients is proposed to avoid possible antirheumatic drug complications.

PMID- 15459812
TI  - HTLV-I env protein acts as a major antigen in patients with HTLV-I-associated
      arthropathy.
AB  - Our objective was to investigate the pathological mechanisms of HTLV-I (human T
      cell leukemia virus type I)-associated chronic arthritis (HAAP) with respect to T
      cell response to HTLV-I viral proteins. We examined T-cell clonality and the
      antigen recognized by T cells from the inflamed synovium of patients with HAAP by
      using histology, a single-strand conformation polymorphism (SSCP) analysis and T
      cell receptor (TCR) sequencing. The SSCP analysis showed oligoclonal expansion of
      T cells in the synovium, suggesting an antigen-mediated stimulation. In contrast,
      there was less clonal expansion in peripheral blood lymphocytes (PBL). The
      expression of HTLV-1 env and tax mRNA was detected in the affected synovium as
      well as in PBL. A number of T-cell clones in the synovium recognized HTLV-I env
      and tax proteins. Twenty-seven (24.9%) of 109 examined T-cell clones in the
      joints were HTLV-I env reactive, and 7 clones (6.4%) were HTLV-I tax reactive.
      Junctional sequence analysis of synovial T cells showed a lack of highly
      conserved amino acid motifs in the complementarity-determining region 3 (CDR3) of
      HTLV-I env and tax reactive T cells, suggesting that these cells recognized
      multiple T-cell epitopes on HTLV-I antigen. These findings suggest that HTLV-I
      env protein acts as a major antigen and may play a role in the development of
      arthropathy in patients with HAAP.

PMID- 15459813
TI  - Clinical evaluation of insulin resistance and beta-cell function by the
      homeostasis model assessment in patients with systemic lupus erythematosus.
AB  - The aim of this preliminary study was to evaluate insulin resistance and
      secretion using homeostasis model assessment (HOMA) in patients with systemic
      lupus erythematosus (SLE). The fasting glucose and insulin concentrations, HOMA
      insulin resistance (IR), HOMA beta-cell, antidouble-stranded DNA antibodies (anti
      dsDNA), C3, C4, and SLE disease activity index (SLEDAI) were determined in a
      total of 58 female SLE patients. All patients were classified into subgroups
      according to the presence of anticardiolipin antibodies (aCL+ vs. aCL-) and
      SLEDAI scores (SLEDAI < 3 vs. SLEDAI > 3). Results showed that SLE patients with
      and without aCL had significantly higher fasting insulin levels, HOMA IR, and
      HOMA beta-cells than controls. Similar results were also found in SLE patients
      with different disease activities. Pearson's correlation analysis showed that
      there was a highly significant correlation of HOMA IR with fasting insulin
      concentration in the SLE patients and SLE subgroups overall. However, HOMA beta
      cells were positively correlated with HOMA IR and fasting insulin level, but
      negatively correlated with fasting glucose concentration in SLE patients overall.
      In conclusion, SLE patients, regardless of the presence of aCL and different
      disease activities, had a higher risk of insulin resistance and abnormal insulin
      secretion than age-matched healthy controls, based on fasting insulin
      concentration, HOMA IR, and HOMA beta-cells.

PMID- 15459814
TI  - The levels of serum-soluble Fas in patients with rheumatoid arthritis and
      systemic sclerosis.
AB  - Different defects in Fas/APO-1 interaction with its ligand or in signaling of
      apoptosis may contribute to autoimmune disease. The aim of this study was to
      examine whether elevated serum-soluble Fas (sFas) levels are associated with
      rheumatoid arthritis (RA) or systemic sclerosis (SSc). sFas level was assayed
      using a sandwich ELISA in serum from 37 patients with RA, 30 patients with SSc
      and 20 healthy controls. The RA patients were classified according to disease
      activity, anatomical joint damage, and the presence of pulmonary involvement.
      Presence of pulmonary fibrosis, CO diffusion capacity (DLCO) and skin score were
      determined in patients with SSc. Serum sFas levels were not significantly
      different between study groups. Serum sFas level in the active RA patients was
      significantly higher than in the patients with inactive disease (p < 0.05). The
      untreated active RA patients had significantly higher sFas level than healthy
      controls (p < 0.05). In RA patients, sFas level was significantly correlated with
      rheumatoid factor titer (p = 0.01), C-reactive protein (p < 0.05), and
      erythrocyte sedimentation rate (p < 0.05). The RA patients with severe joint
      damage had significantly higher sFas level than those with mild joint damage (p <
      0.05). The untreated SSc patients had significantly higher sFas levels than the
      treated SSc patients and healthy controls (p < 0.01). Serum sFas level was not
      correlated with presence of pulmonary fibrosis, DLCO or skin score. The soluble
      Fas molecule may provide a useful additional marker for assessment of disease
      activity and severity in patients with RA.

PMID- 15459815
TI  - An elevated level of IL-10- and TGFbeta-secreting T cells, B cells and
      macrophages in the synovial membrane of patients with reactive arthritis compared
      to rheumatoid arthritis.
AB  - A relative high secretion level of IL-10 and a low secretion of TNF-alpha has
      been described in the synovial fluid and peripheral blood of patients with
      reactive arthritis (ReA), possibly contributing to the persistence of bacteria.
      The role of TGF-beta is less clear. We investigated these cytokines in the
      synovial membrane of patients with ReA and rheumatoid arthritis (RA) and tried to
      identify their cellular source. We used sections from the synovial membrane of 4
      ReA and 4 RA patients which were double stained with immunofluorescence
      antibodies against cell surface markers for T cells (CD3), macrophages (CD68) and
      B cells (CD20) in combination with antibodies against intracellular cytokines TNF
      alpha, IFN-gamma, TGF-beta, IL-4 and IL-10, and quantified these using a
      fluorescence microscope. A lower number of TNF-alpha-secreting cells were found
      in ReA compared to RA: CD3+: 1.78 +/- 0.54% versus 5.02% +/- 0.47% (p = 0.034).
      CD68+: 2.86 +/- 0.52 versus 5.37 +/- 0.53% (p = 0.034), CD20+ : 3.02 +/- 0.42%
      versus 3.58 +/- 0.48% (p > 0.05). A higher number of IL-10 positive cells were
      found in ReA compared to RA: CD3+: 3.27 +/- 1.5% versus 1.13 +/- 0.50% (p =
      0.034), CD68+ 1.23 +/- 0.75% versus 0.83 +/- 0.35% (p > 0.05), CD20+: 3.70 +/-
      1.6% versus 1.6 +/- 1.1% (p > 0.05). A difference between ReA and RA was also
      found for TGF-beta+ T cells: CD3+ 7.86 + 1.5% versus 1.78 + 0.35% (p = 0.032);
      CD20+: 7.91 + 2.1% versus 2.1 + 2.8% (p > 0.05), CD68+: 7.81% + 1.24% versus 2.12
      + 0.28% (p = 0.032). In conclusion, we saw a different cytokine secretion pattern
      in the synovial membrane of ReA and RA. For T cells in ReA we found a cytokine
      secretion profile typical for T regulatory cells 1 (Tr1), with an elevated level
      of IL-10- and TGF-beta-secreting cells. Whether this is due to a more general
      difference in TNF-alpha, IL-10 or TGF-beta production which is genetically
      determined or regulated by T cells remains to be determined.

PMID- 15459816
TI  - Chlamydial infection preceding the development of rheumatoid arthritis: a brief
      report.
AB  - Chlamydia trachomatis-triggered reactive arthritis is a well-documented entity
      that has been extensively described. We do not have a clear understanding about
      the inflammatory oligoarthritis associated with the presence of this organism. It
      is rarely cultured from the synovial fluid, but is usually detectable by
      molecular biological techniques. Typically, Chlamydia trachomatis causes a
      sterile but inflammatory oligoarthritis. We report an unusual case of
      inflammatory monoarthritis in a young woman in whom Chlamydia was isolated from
      the synovial fluid. This is the first case of documented isolation of Chlamydia
      from synovial fluid, which subsequently was diagnosed as rheumatoid arthritis.

PMID- 15459817
TI  - Mixed connective tissue disease associated with antineutrophil cytoplasmic
      antibodies against proteinase-3 and systemic atherosclerosis: a case report.
AB  - A 47-year-old woman presented with facial spasm, swollen fingers and Raynaud's
      phenomenon due to cerebrovascular disorder and mixed connective tissue disease
      (MCTD). Although she was positive for both antineutrophil cytoplasmic antibodies
      against proteinase-3 (PR3-ANCA) and anti-U1 RNP antibodies, she did not meet the
      American College of Rheumatology classification criteria for Wegener's
      granulomatosis (WG). Physical and histopathological examinations revealed severe
      systemic atherosclerosis without any of the traditional risk factors. Elevated
      levels of malondialdehyde-modified LDL and antioxidized LDL autoantibodies, which
      are considered to be key factors in the pathogenesis of atherosclerosis, were
      also detected in the serum of this patient. In this case, systemic
      atherosclerosis might have been linked to these autoimmune reactions.

PMID- 15459818
TI  - Subchondral cyst of the tibia secondary to Wilson disease.
AB  - We present the case of a 40-year-old male patient who had been suffering from
      Wilson disease for over 20 years, whose knee was diagnosed as osteoarthritis
      combined with subchondral cyst of the tibia. Preoperative examinations (X-ray, CT
      and MRI) confirmed the diagnosis. The microscopic examination detected thickening
      of the synovial membrane, and histopathological findings revealed that lymphoid
      cells and plasma cells were infiltrated at the synovial membrane. On copper
      specific staining, no copper pigmentation was identified. However, the energy
      dispersive X-ray (EDX) microanalysis revealed copper pigmentation in high
      concentration. These findings may contribute to our better comprehension of the
      development process of the arthropathy in patients with Wilson disease. The
      combination of subchondral cyst with Wilson disease is extremely rare, as only
      about 16 such cases have been reported in the English literature.

PMID- 15459819
TI  - An underdiagnosed hip pathology: apropos of two cases with gluteus medius tendon
      tears.
AB  - Until recently, gluteus medius tendon tears have been the sort of hip pathology
      that is relatively unknown in the realm of rheumatology. Their diagnosis can pose
      a serious challenge to physicians, despite diligence. In this report we summarize
      two relevant cases and put forward some hints for their evaluation. Magnetic
      resonance imaging is quite beneficial in demonstrating the pathology and ruling
      out other likely pathologies after a prompt physical examination. Physicians
      should exercise care and vigilance in order not to overlook these cases, in which
      prompt physical examination and radiological interventions remain a prerequisite
      in the diagnostic algorithm.

PMID- 15459820
TI  - A giant rheumatoid nodule.
AB  - Subcutaneous rheumatoid nodules occur commonly in advanced cases of rheumatoid
      arthritis and are the most common extra-articular lesion of this disease. We
      present a case of a very unusual giant rheumatoid nodule that developed on the
      lateral side of a knee. The case was devoid of systemic symptoms of arthritis and
      the lesion was limited to a rheumatoid nodule. The nodule was successfully
      treated by surgical excision. However, other new nodules developed in her hand.
      Her clinical course has not been satisfactory.

PMID- 15459821
TI  - Magnetic resonance imaging: a sine qua non in the diagnosis of brucella
      spondylitis.

PMID- 15459822
TI  - Coexistence of Behcet's disease and myasthenia gravis in a patient.

PMID- 15459823
TI  - Takayasu's arteritis and hepatitis C: a new association?

PMID- 15459824
TI  - Linkage disequilibrium and haplotype tagging polymorphisms in the Tau H1
      haplotype.
AB  - We and others have previously detected association of the Tau H1 haplotype on
      chromosome 17 with risk of idiopathic Parkinson disease (PD). The H1 haplotype
      appears to have a fundamental importance in neurodegeneration, as multiple
      studies have shown it is also associated with an increased risk for progressive
      supranuclear palsy, corticobasal degeneration, frontotemporal lobar degeneration
      syndromes, and primary progressive aphasia. Therefore, to divide the H1 haplotype
      into sub-haplotypes that could be more significantly associated with the risk of
      developing PD, and to delimit the genes lying in the H1 haplotype, we analyzed 34
      single nucleotide polymorphisms (SNPs) spanning over 3.15 megabases in the region
      containing Tau. These SNPs are located in or flank the corticotropin-releasing
      hormone receptor 1, presenilin homolog 2, Tau, Saitohin, and KIAA1267 genes.
      Analysis of linkage disequilibrium (LD) using these 34 SNPs suggests that the H1
      haplotype extends over about 1.3 megabases, making it the largest region of LD
      reported to date. Of the 29 SNPs lying in this region of LD, 5 were identified as
      "haplotype tagging" SNPs (htSNPs), capturing 96% of the sample's haplotype
      diversity. Association analysis with these htSNPs revealed a new H1 sub-haplotype
      that is significantly associated with PD ( P<0.02). These results define the
      genes and regulatory regions included in this region of LD, containing an
      important susceptibility allele contributing to increased risk of
      neurodegeneration.

PMID- 15459825
TI  - A G301R Na+/K+ -ATPase mutation causes familial hemiplegic migraine type 2 with
      cerebellar signs.
AB  - Familial hemiplegic migraine (FHM) is an autosomal dominant subtype of migraine
      with hemiparesis during the aura. In over 50% of cases the causative gene is
      CACNA1A (FHM1), which in some cases produces a phenotype with cerebellar signs,
      including ataxia and nystagmus. Recently, mutations in ATP1A2 on chromosome 1q23
      encoding a Na+/K+ -ATPase subunit were identified in four families (FHM2). We now
      describe an FHM2 pedigree with a fifth ATP1A2 mutation coding for a G301R
      substitution. The phenotype was particularly severe and included hemiplegic
      migraine, seizure, prolonged coma, elevated temperature, sensory deficit, and
      transient or permanent cerebellar signs, such as ataxia, nystagmus, and
      dysarthria. A mild crossed cerebellar diaschisis during an attack further
      supported the clinical evidence of a cerebellar deficit. This is the first report
      suggesting cerebellar involvement in FHM2. A possible role for CACNA1A in
      producing the phenotype in this family was excluded by linkage studies to the
      FHM1 locus. The study of this family suggests that the absence of cerebellar
      signs may not be a reliable indicator to clinically differentiate FHM2 from FHM1.

PMID- 15459826
TI  - Mosaic mutations of the FLN1 gene cause a mild phenotype in patients with
      periventricular heterotopia.
AB  - X-linked periventricular nodular heterotopia (PNH) (OMIM 300049) is a neuronal
      migration disorder, associated with mutations of the FLN1 gene (Xq28),
      accompanied by severe epilepsy and normal to mildly impaired cognitive function
      in affected women. The recurrence risk has been estimated to be 50% in daughters
      of affected women, with early post-natal lethality in boys. Mutation analysis
      [denaturing high-performance liquid chromatography (DHPLC) and sequencing],
      performed in a woman and a man with PNH, was suggestive of somatic mosaicism.
      Both patients were investigated using single nucleotide primer extension (SNuPE)
      and DHPLC. To better characterize mosaicism in the affected man, SNuPE-DHPLC
      analysis was also performed on a pool of hair roots and single hair roots. The
      affected woman had features of PNH on magnetic resonance imaging. She had well
      controlled epilepsy and normal cognitive function. She was mosaic for a
      nucleotide insertion (c.568_569ingG). SNuPE-DHPLC findings showed 17% of mutant
      allele. The affected man had classical PNH and was mosaic for an A>G substitution
      (intron 11 acceptor splice site). SNuPE-DHPLC on both leukocyte and hair root DNA
      revealed 42% and 69% of mutant allele. Single hair root analysis confirmed that
      this patient did not harbor the mutation in all ectodermal derivative cells. His
      daughter had not inherited the mutation. Phenotypic heterogeneity associated with
      X-linked PNH may depend on the type of mutation, its location on the protein, as
      well as on somatic mosaicism. Mosaicism can influence the recurrence risk rates
      in affected women. Mosaic mutations in men may not be transmitted to their
      daughters, masking the X-linked nature of the disorder.

PMID- 15459827
TI  - Effects of the rotor pedalling system on the performance of trained cyclists
      during incremental and constant-load cycle-ergometer tests.
AB  - The aim of this study was to determine the effects of Rotor, a new cycle crank
      configuration that effectively allows the pedals to move independently throughout
      the duty cycle, on indices of endurance cycling performance in trained cyclists.
      Ten cyclists (5 Rotor users and 5 non-users; age (mean +/- SD): 22 +/- 5 y;
      VO(2)max: 69.5 +/- 5.1 mL. kg(-1).min(-1)) volunteered to participate in the
      study. On four separate days, the subjects performed four cycle-ergometer tests,
      i.e. two incremental tests and two 20-min tests. An imposed crank rate of 75
      rev.min(-1) was used during all tests. The incremental protocol started at 112.5
      W, and the power output was increased by 37.5 W every 3 min until volitional
      exhaustion. The 20-min tests were performed at a fixed power output equivalent to
      80 % of the highest power output that the cyclists maintained for a complete 3
      min period during incremental tests. Both types of tests were performed with the
      conventional crank system and the Rotor following a counter-balanced, cross-over
      design. Gas exchange parameters were measured in all the tests and blood lactate
      was determined at the end of each 3-min period (incremental tests) and at the end
      of the 20-min tests. A three factor (pedalling system used during the tests x
      habitual pedalling system x power output [incremental tests] or time [20-min
      tests]) ANOVA with repeated measures on power output (incremental tests) or time
      (20-min tests) was used to analyse several indices of performance, e.g. peak
      power output, VO(2)max, lactate threshold, onset of blood lactate accumulation,
      economy, delta, and gross efficiency. No differences (p > 0.05) were found
      between the Rotor and conventional systems for any of the aforementioned
      variables. It seems that the theoretical advantage brought about by the Rotor
      system, i.e. improved contra-lateral cooperation of both legs, would be minimized
      in trained cyclists. Although field studies are needed to assess the possible
      implications, in terms of actual racing, of the new system, commonly used
      indicators of endurance cycling performance do not seem to be improved with the
      Rotor in trained cyclists.

PMID- 15459828
TI  - Evaluation of arm-leg coordination in flat breaststroke.
AB  - This study proposes a new method to evaluate arm-leg coordination in flat
      breaststroke. Five arm and leg stroke phases were defined with a velocity-video
      system. Five time gaps quantified the time between arm and leg actions during
      three paces of a race (200 m, 100 m and 50 m) in 16 top level swimmers. Based on
      these time gaps, effective glide, effective propulsion, effective leg insweep and
      effective recovery were used to identify the different stroke phases of the body.
      A faster pace corresponded to increased stroke rate, decreased stroke length,
      increased propulsive phases, shorter glide phases, and a shorter T1 time gap,
      which measured the effective body glide. The top level swimmers showed short time
      gaps (T2, T3, T4, measuring the timing of arm-leg recoveries), which reflected
      the continuity in arm and leg actions. The measurement of these time gaps thus
      provides a pertinent evaluation of swimmers' skill in adapting their arm-leg
      coordination to biomechanical constraints.

PMID- 15459829
TI  - Acute effects of moderate intensity resistance exercise on bone cell activity.
AB  - Resistance exercise has positive effects on bone mass, but little is known about
      the mechanisms by which this occurs. The purpose of this study was to determine
      if a single bout of moderate intensity resistance exercise alters biochemical
      markers of bone cell activity. Indices of bone turnover were measured in nine
      healthy, untrained men (21.9 +/- 1.2 yrs old), before and following a single 45
      minute session of resistance exercise, and during a control trial. A cross-over
      design was used so that all participants performed both trials in random order.
      Blood samples were collected immediately before, immediately after, and at 1, 8,
      24, and 48 hours post exercise and analyzed for bone-specific alkaline
      phosphatase (BAP), type I collagen propeptide (PICP), and type I collagen N
      telopeptide (sNTX). Urine from the second morning void was collected over four
      days (day before, day of, and two days following exercise) and analyzed for type
      I collagen N-telopeptide (uNTX). Exercise resulted in a significant increase (p <
      0.05) in the ratio of biochemical markers of bone formation to bone resorption
      eight hours post exercise, largely due to a decrease in sNTX. Markers return to
      baseline within 24 hrs. These data suggest that moderate intensity resistance
      training acutely reduces bone resorption, leading to a favorable change in
      overall bone turnover, for at least 8 hours post exercise in untrained young men.
      Further work is needed to determine if long-term benefits to bone strength follow
      with persistent training.

PMID- 15459830
TI  - Effect of voluntary exercise on the expression of IGF-I and androgen receptor in
      three rat skeletal muscles and on serum IGF-I and testosterone levels.
AB  - The effects of anabolic agents and training on skeletal muscle are believed to be
      mediated by a variety of growth and transcription factors. Among these regulatory
      proteins, insulin-like growth factor-I (IGF-I) and androgen receptor (AR) play a
      crucial role. The purpose of this study was to investigate the effects of wheel
      running on IGF-I and AR mRNA expression in three distinct rat skeletal muscles
      (i.e., gastrocnemius, vastus lateralis, and soleus), as well as on the serum
      levels of IGF-I and testosterone. Twenty male Wistar rats were housed in cages
      with free access to running wheels for 12 weeks, while nine rats served as
      controls. Analysis of the mRNA expression of IGF-I and AR using real time RT-PCR
      revealed no significant differences between the trained and untrained rats in any
      of the muscles studied. Enzyme immunoassay showed significantly lower serum
      levels of IGF-I and testosterone in the trained compared to the untrained
      animals. These results suggest that chronic exercise in wheels does not affect
      IGF-I and AR mRNA levels in rat skeletal muscle, while decreasing the circulating
      levels of two anabolic factors, i.e., IGF-I and testosterone. It is concluded
      that IGF-I, AR and testosterone seem to play a marginal role during the
      adaptation process of rat skeletal muscle to long-term wheel running.

PMID- 15459831
TI  - Fatigue and recovery after high-intensity exercise. Part II: Recovery
      interventions.
AB  - The purpose of this study was to determine the effect of three types of recovery
      intervention to neuromuscular function after high-intensity uphill running
      exercise. The 20-min recovery interventions were (i) passive, (ii) active
      (running at 50 % of maximal aerobic speed), and (iii) low-frequency
      electromyostimulation. Evoked twitch and maximal voluntary contractions of knee
      extensor muscles (KE) and EMG of the vastus lateralis and vastus medialis were
      analysed immediately after the exercise, 10 min after the end of the recovery
      periods, and 65 min after the exercise (Post65). An all-out running test was also
      performed 80 min after the end of the fatiguing exercise. No significant
      differences were noted in any measured parameters but a tendency to a better
      performance during the all-out test was found after the electromyostimulation
      intervention (297.5 +/- 152.4 s vs. 253.6 +/- 117.1 s and 260.3 +/- 105.8 s after
      active and passive recovery, p = 0.13 and p = 0.12, respectively). At Post65,
      isometric maximal voluntary contraction torque did not return to the pre-exercise
      values (279.7 +/- 86.5 vs. 298.7 +/- 92.6 Nm, respectively; p < 0.05). During
      recovery, electrically evoked twitch was characterized by an increase of peak
      torque, maximal rate of force development and relaxation (+ 24 - 33 %; p < 0.001)
      but these values were still lower at Post65 than pre-exercise. Amplitude and
      surface of the M-wave decreased during recovery. These results show that the
      recovery of the voluntary force-generating capacity of KE after an intermittent
      high-intensity uphill running exercise do not depend on the type of recovery
      intervention tested here. It can also be concluded that the recovery of twitch
      contractile properties does not necessarily follow that of maximal muscle
      strength.

PMID- 15459832
TI  - The effects of physical exercise on the concentrations of ferritin and
      transferrin receptor in plasma of male judoists.
AB  - The aim of the study was to assess the within-subject (day-to-day) variability
      for iron status variables: ferritin (ferr) and soluble transferrin receptor
      (sTfR) concentrations in plasma and the sTfR/log ferr index in athletes subjected
      daily to high physical loads. Blood was sampled in the morning from 8 healthy
      male elite judoists, aged 20 - 31 years, for 10 consecutive days while at
      training camp. Mean concentrations of ferritin and sTfR in plasma for the 10 day
      period were 32.0. 1.771(+/-1) and 2.41. 1.324(+/-1) mg/l, respectively. The
      average within-subject, day-to-day variability for ferritin was 27.4 % (range: 16
      - 44 %), and was much lower for sTfR (6.7 %; range: 4 - 15 %). Ferritin
      concentrations were significantly, albeit weakly, correlated with training loads
      on the preceding day (r = 0.256; p < 0.05) and with creatine kinase (CK)
      activities on the same day (r = 0.397; p < 0.001), while sTfR did not correlate
      with either training loads or CK activities. Mean day-to-day variability for the
      sTfR/log ferr index was 11.8 % (range: 5 - 21 %), i.e. markedly lower than for
      ferritin. Although the physical load-induced changes in iron metabolism indices
      in male subjects were similarly oriented as in the earlier reported female ones
      representing the same sport, the magnitude of those changes was less pronounced
      than in the females. This was evidenced by a markedly lower within-subject day-to
      day variability in ferritin, still significant but weak correlation between load
      magnitude and ferritin levels, and a significant, negative correlation between
      ferritin and sTfR concentrations, not found previously in the female athletes.
      However, despite lower variability in ferritin than in women, the exercise
      induced ferritin increases in male athletes might make a reliable assessment of
      iron stores in them difficult. The present results confirm our earlier reports
      that sTfR levels are stable under high physical loads, thus making them a useful
      indicator of iron status. Also sTfR/log ferr index is of a much higher diagnostic
      value than ferritin, despite high variability of the latter. That index is
      particularly valuable in detecting iron-deficient erythropoiesis.

PMID- 15459833
TI  - Leukocyte heat shock protein expression before and after intensified training.
AB  - The purpose of the current research was to test the hypothesis that exercise
      induced leukocyte heat shock protein (HSP) expression is increased during periods
      of intensified exercise training. Seven male endurance cyclists carried out tests
      of maximal oxygen consumption and endurance capacity. These standard exercise
      tests were carried out prior to and following 6 days of prescribed intensified
      training. Sampled leukocytes were examined for Hsp27 and Hsp70 expression using a
      Fluorescence Activated Cell Scanner (EPICS XL, Coulter). During a period of
      overreaching, as signified by a drop in time to fatigue following the intensified
      training period (p = 0.02), the number of extracellular Hsp27 positive
      granulocytes increased in response to the VO(2)max test. Acute, intracellular HSP
      responses were observed in both baseline and overreached conditions. The present
      study showed that a period of intensified training caused adaptations in the
      acute heat shock protein exercise response, reflected by a greater increase of
      cell surface HSP positive leukocytes following heavy training.

PMID- 15459834
TI  - Norandrosterone and noretiocholanolone concentration before and after submaximal
      standardized exercise.
AB  - 19-Norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) are the two main
      urinary indicators used to detect illegal use of nandrolone. Recent studies
      showed that 19-NA and 19-NE can be endogenously produced in non-treated humans.
      The concentrations were close to the threshold of the International Olympic
      Committee (IOC), i.e. 2 ng/ml for men and seem to increase after prolonged
      intense effort. Androgens are involved in the biosynthesis of estrogens and
      estrogen has a protective effect against skeletal muscle damage following
      eccentric exercise. Furthermore, the testicular tissue can synthesize 19
      norandrogens from androgens, we hypothetisize that the 19-norandrogen production
      might be influenced by muscle damage following eccentric exercise. Therefore the
      purpose of this study is to examine if three different exercise methods will
      influence the urinary concentration of 19-NA and 19-NE in healthy young subjects.
      Fifteen amateur hockey players undertook a 30 min submaximal standardized
      exercise protocol. They were randomised for three different types of exercise,
      namely a cycle ergometer test (cyclic muscle activity), a treadmill test
      (concentric muscle activity), or a bench-steptest (eccentric muscle activity) at
      a target heart rate corresponding to 65 % (+/- 5 %) of Karvonen heart rate. Urine
      samples were obtained before the test and 60 min and 120 min after the end of
      exercise. Subjects completed a Likert scale of muscle soreness before and 12 h
      after exercise. 19-NA and 19-NE were determined by gas chromatography-tandem mass
      spectrometry (GC-MS-MS). Baseline urinary 19-NA and 19-NE concentrations were
      under limit of detection of 0.05 ng/ml, except for one sample (0.13 ng/ml). No 19
      NA or 19-NE could be detected post exercise. In our experimental conditions, the
      exercise mode (eccentric or concentric) had no impact on 19-NA or 19-NE
      excretion. Our findings confirm that the current International Olympic Committee
      threshold level for nandrolone metabolites is sufficiently high to avoid false
      positive cases.

PMID- 15459835
TI  - Inhaled salbutamol and endurance cycling performance in non-asthmatic athletes.
AB  - Beta(2)-adrenergic agonists are important therapeutic agents for the prevention
      and treatment of (exercise-induced) asthma in athletes, but may have ergogenic
      effects. In this study we investigated whether inhalation of a supra-therapeutic
      dose of 800 microg salbutamol before exercise affects endurance performance
      during a cycling trial in non-asthmatic athletes. In a double-blind, randomized
      cross-over study, 16 athletes performed two trials, where they had to perform a
      certain amount of work as fast as possible on a cycle ergometer, 30 minutes after
      inhalation of 800 micro g salbutamol or placebo. Peak expiratory flow (PEF),
      forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV(1))
      were measured before and after exercise and blood samples were obtained before
      and during exercise. Cycling performance time was 4010.2 +/- 327.7 s after
      placebo inhalation and 3927.6 +/- 231.3 s after inhalation salbutamol (p < 0.05).
      Although salbutamol inhalation increased plasma free fatty acids, glycerol and
      lactate concentrations and decreased plasma potassium concentrations at rest, no
      differences between placebo and salbutamol in these variables were found during
      exercise. PEF and FEV(1) were increased after salbutamol inhalation at rest
      compared with placebo, but the difference between placebo and salbutamol after
      exercise was no longer significant. Inhalation of a supratherapeutic dose of 800
      micro g salbutamol improved endurance cycling performance by 1.9 +/- 1.8 % in non
      asthmatic athletes, which indicates that this route of administration does not
      exclude the possibility of an ergogenic effect of beta(2)-adrenergic agents in
      athletes. The increase in performance was not explained by changes in plasma
      concentrations of free fatty acids, glycerol, lactate, and potassium during
      exercise or by changes in ventilatory parameters at rest and after exercise.
      Therefore, the mechanism of the increase in performance remains to be determined.

PMID- 15459836
TI  - Effects of brisk walking on static and dynamic balance, locomotion, body
      composition, and aerobic capacity in ageing healthy active men.
AB  - This work analyses the short-term physiological and neurophysiological effects of
      a brisk walking programme in ageing, healthy, active men. Twenty-one men 63 to 72
      years of age were recruited and separated into 2 groups. One group performed a
      walking programme (WP) (n = 11) and another served as control (C) group (n = 10).
      The walking programme lasted for twelve weeks and included five sessions per
      week. Several parameters were assessed before and after the programme for the WP
      group. The same tests were performed (separated by twelve weeks) in group C.
      During each assessment, the subjects were put through static and dynamic balance
      tests, spatio-temporal gait analysis, body composition measurements and
      determination of aerobic capacity and bone mineral density. The statistic
      analysis showed a significant improvement in dynamic balance performance,
      especially in lateral sway when the subjects kept their eyes open, an increase of
      VO(2) max and loss of fat mass in the WP group. However, no alterations appeared
      in spatiotemporal gait characteristics, static balance performance, lean mass or
      bone mineral density (total body and hip). According to these results, this
      walking programme may have positive effects on preventing ageing subjects from
      falling.

PMID- 15459837
TI  - Cardiorespiratory fitness of males and females of northern Finland birth cohort
      of 1966 at age 31.
AB  - This study aimed to measure cardiorespiratory fitness of about 9000 males and
      females at age 31, to produce the reference values and relate them to the level
      of physical activity and body mass index (BMI). Study population was the Northern
      Finland birth cohort of 1966. At age 31, 8786 persons responded to a postal
      inquiry including questions about physical activity and 5497 of them also
      performed a step test. A sample of 123 persons performed a maximal exercise test
      with direct measurement of peak oxygen uptake (VO(2peak)). This was done to
      develop VO(2peak) prediction models on the basis of heart rate after a step test,
      BMI and frequency of brisk physical activity. These models were used to calculate
      VO(2peak) for the whole study population. Mean VO(2peak) +/- standard deviation
      was 43.0 +/- 4.6 ml.kg(-1).min(-1) in 4071 males and 34.3 +/- 4.3 ml.kg(-1).min(
      1) in 4367 females. A graded dose-response relationship was observed in males and
      females between the frequency of participation in brisk exercise and VO(2peak).
      Similar dose-response relationship was also observed in overweight and obese
      persons, although the level of VO(2peak) was lower in persons with increased BMI.
      At age 31, very low levels of VO(2peak) seemed to be associated with a
      combination of infrequent participation in brisk exercise and increased BMI.
      These reference values can be used in the interpretation of fitness test results
      and in physical activity counselling.

PMID- 15459838
TI  - Effect of competitive training on T-cell mediated immune function in Master's
      female athletes.
AB  - Interest in the effects of intense exercise training on immune function has grown
      over the past decade. Currently, data on the immunocompetence of female endurance
      athletes are limited and do not present a clear picture. The objective of this
      study was to compare the T-cell mediated immune function of female Master's
      athletes (41 +/- 4.3 yr) during peak training with age-matched non-athletes (42
      +/- 3.6 yr) using non-specific and antigen-specific stimulation. Samples of
      peripheral venous blood were taken at rest for determination of total circulating
      T-cell number, sub-population number and CD4 + helper T-cell function. No
      significant difference in total circulating T-cell number or in the number of
      cells in each of the tested lymphocyte subpopulations was detected between
      athletes (n = 19) and non-athletes (n = 20). In athletes, 7.9 % of cells
      responding to non-specific (PMA and ionomycin) stimulation produced IL-2 versus
      3.9 % of responding cells in non-athletes (p < 0.05). No statistical difference
      was noted between athletes and non-athletes in the percentages of antigen
      responding CD4 + helper T-cells producing IL-2 (2.4 % and 2.3 %, respectively).
      Results of this study suggest that T-cell mediated immune function may not be
      compromised in female Master's athletes during periods of competitive training.

PMID- 15459839
TI  - [Color vision and the diagnosis of reduced visual acuity].
AB  - Unexplained visual acuity loss requires a systematic approach to gather as many
      findings of diagnostic value as possible. Most retinal or optic nerve diseases
      are accompanied by color vision disorders. The type and severity of color vision
      disorders may provide additional diagnostic or guiding information or may uncover
      aggravating or simulating factors.

PMID- 15459840
TI  - [Individual postoperative refraction after cataract surgery -- a comparison of
      optical and acoustical biometry].
AB  - BACKGROUND: Optical biometry with the IOL-Master is an innovative technique that
      claims to improve the refractive results of cataract surgery compared to
      acoustical biometry. METHODS: In 140 consecutive non-selected eyes prior to
      cataract surgery firstly an optical biometry (IOL-Master, Zeiss, V.2.02) and
      secondly an ultrasound biometry (Sonomed) were carried out. Cataract surgery was
      performed using either a PMMA-IOL (n = 56) or an acrylic IOL (n = 84). The PMMA
      IOL's were implanted in the capsular bag via a scleral tunnel. The acrylic-IOL's
      were implanted via a clear cornea incision in the capsular bag. The length of the
      globe was analysed and the deviations between the postoperative refraction after
      3 month and the preoperative planned refraction were compared. RESULTS: The mean
      axial length difference between optical biometry and acoustical biometry was 0.19
      mm in the PMMA-lens group and 0.16 mm in the acrylic-lens group. The deviation of
      postoperative refraction (spherical mean) from the planned refraction was 0.46 +/
      0.88 D in the PMMA-IOL group and 0.25 +/- 0.77 D in the acrylic IOL group when
      biometry was performed by ultrasonography. When optical biometry was performed
      the respective values were 1.15 +/- 0.83 D in the PMMA-IOL group and 0.84 +/-
      0.75 D in the acrylic IOL group. The differences in mean postoperative refraction
      of optical and acoustical biometry can be compensated by adaptation of the A
      constants. The standard deviation of the difference between the postoperative
      refraction and the preoperatively planned refraction - that means the individual
      deviations between postoperative refraction and preoperatively planned refraction
      - were almost identical in optical and acoustical biometry. CONCLUSION: Optical
      biometry represents a significant simplification in the course of investigation
      prior to cataract surgery. The claim of optical biometry, however, to gain a
      higher precision and thus a significantly better prediction of individual
      postoperative refraction after cataract surgery is not yet fulfilled.

PMID- 15459841
TI  - [Cataract surgery under topical anesthesia with oral anticoagulants].
AB  - BACKGROUND: Approximately 14 % of cataract surgery patients receive blood
      thinning agents. In a prospective study, the influence of oral anticoagulants on
      intraoperative and postoperative hemorrhages in patients undergoing cataract
      surgery in topical anesthesia was investigated. PATIENTS AND METHODS: 128
      patients presenting for cataract surgery under oral anticoagulation were
      included. The mean preoperative prothrombin time was 39 +/- 18 %. Most patients
      (81 %) continued their oral anticoagulation (prothrombin time 34 +/- 13 %). All
      surgeries were performed in topical anesthesia. RESULTS: In 9 patients (7 %) an
      ocular hemorrhagic event was observed. These were not sight-threatening and
      resorbed spontaneously within a few days. Only one patient (0.8 %) had a slight
      hemorrhage in the anterior chamber. There were no differences (P > 0.05) between
      patients with or without hemorrhagic complications in the postoperative visual
      acuity, the intraocular pressure, the prothrombin time or the discontinuation of
      oral anticoagulants. CONCLUSIONS: Cataract surgery in topical anesthesia under
      oral anticoagulation did not increase the risk of sight-threatening hemorrhages.
      The continuation of oral anticoagulation seems particularly indicated for
      ambulatory cataract surgery.

PMID- 15459842
TI  - [Impact of prostaglandin-F(2alpha)-analogues and carbonic anhydrase inhibitors on
      central corneal thickness -- a cross-sectional study on 403 eyes].
AB  - BACKGROUND: Histological changes of, in particular, collagen and extracellular
      matrix after administration of topical prostaglandin F(2alpha)(PGF (2alpha))
      analogues have been reported. In view of this observation, we investigated the
      influence of PGF(2alpha) analogues on the central corneal thickness. PATIENTS AND
      METHODS: In a non-randomized, controlled, cross-sectional study, 403 eyes from
      208 consecutive patients were examined: 149 eyes (normals/controls) and 79 with
      ocular hypertension (OHT), 119 eyes with primary open angle glaucoma (POAG) and
      56 eyes with normal tension glaucoma (NTG). One experienced ophthalmologist
      measured the central corneal thickness (CCT) using ultrasound pachymetry (Tomey
      AL-2000, sequence of 5 measurements with an SD < 3 microm). The central corneal
      power was measured with the Zeiss keratometer. Depending on the topical
      treatment, the patients were classified into 4 groups: A) PGF(2alpha) analogues
      (n = 78), B) carbonic anhydrase inhibitors (n = 26), C) combination of PGF
      (2)(alpha) analogues and carbonic anhydrase inhibitors (n = 41), D) none of these
      drugs (n = 258). T tests and multiple linear regression analyses were used for
      statistical analysis. RESULTS: CCT was decreased significantly (p < 0.01 each) in
      eyes treated with PGF(2alpha) analogues (group A: 529 +/- 34 microM), in
      comparison with the untreated and non-glaucomatous eyes (part of group D: 542 +/-
      35 microM, n = 148), untreated glaucomatous/OHT eyes (part of group D: 563 +/- 37
      microM, n = 110), eyes treated with carbonic anhydrase inhibitors (group B: 561
      +/- 32 microm) and eyes with a topical application of both PGF (2)(alpha)
      analogues and carbonic anhydrase inhibitors (group C: 555 +/- 48 microM. No
      correlation was found between CCT and diagnosis (OHT, POAG, NTG, control),
      gender, central corneal power, and intraocular pressure in a multivariate
      analysis. CONCLUSIONS: The present findings suggest that the topical application
      of prostaglandin F(2alpha) analogues onto the cornea reduces the central corneal
      thickness significantly. These changes might be attributed to effects of
      PGF(2alpha) analogues on the extracellular matrix of the corneal stroma via
      upregulation of matrix metalloproteinases. In clinical practice, corneal thinning
      under local PGF (2)(alpha) analogue treatment could result in underestimation of
      intraocular pressure levels as measured by applanation tonometry.

PMID- 15459843
TI  - [Agreement between clinical evaluation, Heidelberg-Retina-Tomograph (HRT) and
      Nerve Fiber Analyzer (GDx) in glaucoma diagnosis].
AB  - BACKGROUND: We have made a comparison of clinical evaluation, Heidelberg-Retina
      Tomograph (HRT) and Nerve Fiber Analyzer (GDx) in diagnosing glaucoma. MATERIALS
      AND METHODS: One eye of 38 glaucoma patients and 26 non-glaucoma patients was
      examined with HRT and GDx. Assignment of the patients into the two groups by
      clinical evaluation was performed on the basis of visual field and optic disc
      results. As classification criterion for glaucoma/non-glaucoma by means of the
      instruments we employed the statistical classification of the HRT and "the
      number" of the GDx. Statistical analysis was performed with Cohen's kappa and
      McNemar tests. Additionally, ROC curves for evaluation of the sensitivity and
      specificity of the glaucoma classification are demonstrated for HRT and GDx.
      RESULTS: Agreement between clinical evaluation and HRT was moderate (Cohen's
      kappa = 0.43), there was no significant over- or underdiagnosis by HRT (p =
      0.48). Agreement between clinical evaluation and GDx (diagnosis of glaucoma when
      "the number" > 50) was bad (Cohen's kappa = 0.27) with a significant
      overdiagnosis by GDx compared to clinical evaluation (p < 0.05). Agreement
      between clinical evaluation and GDx (diagnosis of glaucoma when "the number" >
      40) was better (Cohen's kappa = 0.54), there was no significant over- or
      underdiagnosis by GDx (p = 0.79). ROC curves for glaucoma classification showed
      no difference between HRT and GDx (area under the curve: HRT = 0.8, GDx = 0.78).
      CONCLUSIONS: Because of the only moderate agreement between clinical evaluation
      on the one hand and HRT and GDx classification on the other hand for the
      discrimination between glaucoma and non-glaucoma, the clinician should not
      completely rely on the instrument-derived glaucoma classification.

PMID- 15459844
TI  - [Prospective comparison of the new indentation tonometer TGdC-01, the non-contact
      tonometer PT100 and the conventional Goldmann applanation tonometer].
AB  - BACKGROUND: This study aimed to compare the results of newer tonometric
      techniques with standard tonometry for the examples of the Goldmann applanation
      tonometry (GAT), the indentation tonometer "TGDc-01" and the non-contact
      tonometer "PT 100". PATIENTS: The study was conducted on a total of 52 healthy
      subjects. The IOP was measured in each subject on both eyes with all three
      methods. There were 27 males (51.9 %), 25 females (48.1 %) with an average age of
      28.5 years, with a minimum of 13 and a maximum of 79 years. RESULTS: There was no
      statistically significant difference between the non-contact and the Goldmann
      applanation tonometry. The measurements were 0.4 mmHg lower, no difference for
      the left or right side was seen. For IOP higher than 15 mmHg - 0.88 mmHg lower
      and for IOP lower 15 mmHg - 0.15 mmHg. The results for the "TGDc01" were 0.82
      mmHg lower than GAT, the standard deviation was a little higher with 2.9 mmHg
      compared to 2.67 mmHg for GAT. For IOP higher than 15 mmHg they rose up to - 2.28
      mmHg, for IOP lower than 15 mmHg the results for "TGDc-01" were only - 0.2 mmHg
      lower. There was also an effect with respect to the side, on the right eye the
      difference was significant with 3.03 mmHg (p = 0.006), in contrast to the left
      eye with 2.69 mmHg (p = 0.235). For "TGDc01" the standard deviation was higher
      with 2.9 mmHg compared to 2.6 mmHg for "PT 100". CONCLUSIONS: The non-contact
      tonometer showed no clinical relevant difference compared with GAT for measuring
      IOP. The indentation tonometer showed differences for precision, for higher
      tension IOP the measurement was lower compared with GAT. There was also a
      significant side difference using the "TGDc-01".

PMID- 15459845
TI  - [Is combined surgical correction of horizontal and vertical squint of value in
      graves' ophthalmopathy?].
AB  - BACKGROUND: In Graves' ophthalmopathy squint can be corrected in about two-thirds
      of the patients with a single recession of an inferior or medialis rectus muscle.
      The dose-effect correlation is linear over a wide range. Combined vertical and
      convergent misalignments are rare. The aim of this study was to evaluate the dose
      effects in combined recessions of medialis and inferior rectus muscles. MATERIAL
      AND METHODS: The dose-effect of combined recessions (one side medialis and
      inferior n = 28, both sides medialis and one side inferior n = 9) was evaluated.
      The control groups were patients with Graves' ophthalmopathy, who had single
      inferior recession (n = 187), single medialis recession (n = 37) and bilateral
      medialis recession (n = 44). RESULTS: Small hypotropias (up to 5 degrees ) at the
      eye with the poorer abduction disappear after single (17 of 21) or bilateral (11
      of 19) medialis recessions. This obvious influence of horizontal recession on the
      vertical angle leads to a higher dose-effect for the inferior recessions in
      combined surgery, and was stronger for bilateral cases (from 2.0 degrees to 2.7
      degrees /mm recession) than for unilateral cases (from 2.0 degrees to 2.2 degrees
      /mm recession). The dose-effect for medialis recession in combined surgery
      increased for the unilateral procedures only from 1.7 degrees to 1.8 degrees /mm
      recession and not for the bilateral medialis recession. CONCLUSIONS: The dose
      effect for combined medialis and inferior recessions is enhanced and varies to a
      much higher degree in comparison to single muscle recessions. Because of the
      higher variability, patients who need both medialis and inferior recession should
      be better operated in separate sessions, beginning with the horizontal muscle(s).

PMID- 15459846
TI  - [Solid limbal dermoid in an 80-year-old patient].
AB  - BACKGROUND: Typically solid limbal dermoids are excised in pre-school age unless
      a high irregular astigmatism and its risk for amblyopia lead to an earlier
      intervention. CASE REPORT: An 80-year-old lady from a rural area complained about
      a burning, tearing and foreign body sensation of the left eye for two months. In
      the past two years she had recognized that an extraocular prominence which had
      been present since birth had shown a tendency to grow. Slit lamp examination
      showed a markedly prominent and vascularized limbal tumor from 3.30 to 7.00
      o'clock. Paralleling the border of the mass there was a bow-shaped stromal lipoid
      deposit reaching from limbus to limbus. Gonioscopic examination revealed a deep
      penetration of the process almost into the anterior chamber. The tumor was
      excised and some fatty tissue adjacent to Descemet's membrane was left.
      Histological assessment brought us to the diagnosis of a chronically irritated,
      predescemetal limbal dermoid with marked secondary vascularization,
      epidermalization, elastoid degeneration and degenerative arcus lipoides.
      CONCLUSIONS: The excision of the limbal dermoid in the described case was
      performed in the later stage of life. When indicated cosmetically or medically,
      surgery should typically take place in pre-school age and be performed as a
      lamellar excision.

PMID- 15459847
TI  - [Tear examinations in primary peripheral lipid keratopathy].
AB  - The authors report a case of a bilateral peripheral lipid keratopathy, rising
      differential diagnostic points as well. After several year-long follow-up period
      the peripheral corneal opacity left the center unaffected. The diagnosis was
      confirmed by tear examinations which disclosed elevated level of fatty and
      phosphorous content compared to healthy control eyes.

PMID- 15459848
TI  - [Unilateral ptosis in the background of unilateral corneal arcus lipoides -- a
      case report].
AB  - BACKGROUND: Arcus lipoides corneae is a common bilateral degenerative disorder
      with ageing but only rarely occurs unilaterally. Clinically visible cream
      coloured ring-shaped corneal opacities are caused by excessive lipoid deposits in
      the corneal stroma. Our aim is to discuss theoretical aspects of the possible
      impact and pathomechanism of unilateral ptosis in unilateral arcus lipoides. CASE
      REPORT: The authors report the case of a 70-year-old female patient who was
      treated for chronic pancreatitis and hyperlipoproteinemia. She had congenital
      ptosis on the left side, and an arcus lipoides corneae in her left eye. The
      patient underwent extracapsular cataract extraction, and irregular high-grade
      astigmatism developed. An irregularity of the wound healing was apparent from the
      keratometric values, which decreased after removal of the corneal sutures.
      CONCLUSION: The known etiological factors of unilateral arcus lipoides, like
      contralateral stenosis of the internal carotid artery, traumatic or iatrogenic
      hypotony, chronic iridocyclitis of the eye were absent in our patient.

PMID- 15459849
TI  - [Bifocal photography using the HRA -- an optimized method to evaluate tIOL's
      axial orientation].
AB  - BACKGROUND: The assessment of axial orientation of toric IOLs (tIOLs) by
      monofocal photography can be deteriorated due to intrinsic errors e. g. globe
      rotation, head inclination or inadequate camera adaption and slide projection.
      METHOD: In a 67 years old female a tIOL was implanted after penetrating
      keratoplasty for correction of high corneal astigmatism. A sequence of two fundus
      and two tIOL photographs (bifocal photography) was taken in a time interval of 3
      months using the HRA II (Heidelberg Retina Angiograph II). A reference at the
      fundus was defined using two characteristic markers. The axial fundus orientation
      between the markers was overlaid to the line defined by the tIOL axis markers.
      The angular offset/distance between the fundus orientation line and the tIOL
      marker line was analyzed for each bifocal image at different time points.
      RESULTS: The comparison of axial tIOL orientation between both different tIOL
      images revealed a rotation angle of 13 degrees (monofocal photograph). In
      contrast, using the bifocal photography and digital overlay technique the fundus
      line as a reference the tIOL rotated 1 degrees and 4 degrees from the first to
      the second time point of photography. Thus, the real rotation angle of tIOL
      measured only 3 degrees. CONCLUSION: The bifocal photography with constant head
      position has the potential to minimize the intrinsic error in documentation of
      axial orientation of tIOL.

PMID- 15459850
TI  - [Bilateral AION after the combined therapy of hepatitis C with PEG-interferon
      alpha2B and ribavirin].
AB  - INTRODUCTION: Chronic hepatitis C-therapy is limited to the combined use of PEG
      ylated interferons and ribavirin. Side effects of this therapy include retinal
      changes that manifest with bleeding, cotton wool spots and/or thrombosis.
      PATIENT: A 51-year-old man presented with a sudden decrease of visual acuity.
      Chronic hepatitis C was known for the duration of 6 months and treated for 3
      months with a combined therapy of PEG-interferon alpha2B and ribavirin. A sudden
      visual loss occurred in the right eye and bilateral visual field defects were
      detected. Ophthalmoscopic examination revealed bilateral papilloedema. After
      withdrawal of PEG-interferon alpha2B and ribavirin, a standard haemodilution
      therapy was started without functional improvement. After papilloedema
      regression, a beginning secondary atrophy of the optic nerve was diagnosed
      bilaterally. Vision did not improve. CONCLUSION: The ocular side effects of
      combined hepatitis C therapy with PEG-interferon alpha2B and ribavirin range from
      mild retinal changes to severely impaired vision. Treatment should be carried out
      in co-operation with an ophthalmologist. With respect to the uncertain
      effectiveness of hepatitis C therapy with interferon alpha2B and ribavirin,
      therapy should be stopped as soon as severe ophthalmological complications occur.

PMID- 15459851
TI  - [Laudation for professor Wolfgang Papst on the occasion of his 80th birthday].

PMID- 15459852
TI  - [In memoriam: professor Matthias Korth].

PMID- 15459853
TI  - [Petrus Hispanus (1205? - 1277) -- ophthalmologist, logician, pope].

PMID- 15459862
TI  - [Pro and contra -- vesicoureteral reflux in childhood -- endoscopic
      administration vs. open reconstruction].

PMID- 15459863
TI  - [Resection of an interfering symphysis "spur" in the small pelvis for better
      exposure of the prostate-urethra transition].

PMID- 15459864
TI  - [Urinary diversion via a continent ileal reservoir: clinical results in 12
      patients].

PMID- 15459866
TI  - [Family physician centered care -- freeing from practice dues is tricky].

PMID- 15459868
TI  - [Personal marketing and development: challenge for hospitals].

PMID- 15459869
TI  - [Cross-section diagnosis of tumors of the kidney and prostate gland: CT and MRI].
AB  - Computed tomography (CT) and magnetic resonance imaging (MRI) underwent
      significant technical advances in the past ten years, especially in the
      diagnostic evaluation of renal tumors. Either modality can perform unenhanced and
      contrast enhanced imaging with high resolution display of three-dimensional data
      sets of the entire abdomen including the arterial and the parenchymatous
      perfusion phase after injection of contrast medium. Multiplanar reconstructions
      of these three-dimensional data allow the display in any chosen orientation. The
      maximum intensity projection can create CT and MR angiograms. For the diagnosis
      of renal tumors, both modalities offer the possibility of a detailed
      visualization of both the parenchyma and the arterial and venous vessels, leading
      to an efficient preoperative work-up. For the MRI diagnosis of the prostate
      cancer, the achievable accuracy depends on the applied coil technique and on the
      available clinical information as well as on the experience of the examiner. For
      the preoperative MRI staging of prostate cancer, the accuracy has been stated to
      be between 51 % and 97 %.

PMID- 15459870
TI  - [Ultra-low-dose CT to search for stones in kidneys and collecting system].
AB  - Unenhanced computed tomography (CT) has a sensitivity of 97.7 to 100 % for the
      detection of urolithiasis. Using a modified examination protocol, the radiation
      exposure of a CT examination can be reduced to the level of a single conventional
      radiographic view of the abdomen (ultra-low-dose CT), assuming the examination is
      performed on a modern multirow CT. Automatic postprocessing of thin-section
      images can delineate stones on coronal images. In 30 patients, ultra-low-dose CT
      could detect more stones (6 renal and 19 ureteral stones) than ultrasonography.

PMID- 15459871
TI  - [Fetal and neonatal kidney function. Implications for fetal urinary tract
      abnormalities].
AB  - High-resolution sonography provides the opportunity for prenatal detection of
      fetal anomalies of the urinary tract. In view of various options of prenatal
      urinary diversion to alleviate obstruction, it has become a scientific goal to
      measure fetal renal function and to determine the prognosis of urinary tract
      malformations. The article outlines the accumulated knowledge of the development
      of fetal renal function and the diagnostic possibilities offered by sonography
      and by laboratory test with focus on the chemistry of the amniotic fluid. Taking
      into consideration the high risks of prenatal intervention, these findings are
      discussed as to their relevance for the clinical management of pregnancies
      complicated by fetal urinary tract abnormalities. Lastly, criteria are proposed
      for the decision making in clinical practice.

PMID- 15459872
TI  - [An unusual complication of extracorporeal shock wave lithotripsy: rupture of the
      kidney with consecutive nephrectomy].
AB  - INTRODUCTION: Extracorporeal shockwave lithotripsy (ESWL) plays a major role in
      the treatment of urolithiasis. It has a high success rate, and spectrum and
      incidence of treatment-related morbidity are low. CASE REPORT: A 66-year-old male
      patient underwent ESWL treatment for an 8 mm medium-sized stone in the left
      kidney. During the subsequent post-interventional phase he experienced persistent
      flank pain, macrohematuria and protracted hemodynamic instability. An acute CT
      scan displayed a massive kidney rupture. Emergency lumbar exploration of the left
      kidney revealed multiple lacerations in the renal parenchyma and a nephrectomy
      was carried out. CONCLUSION: This is the second internationally reported case
      study in which nephrectomy was necessitated after ESWL treatment due to multiple
      ruptures of the kidney. In view of the increasing use of ESWL in outpatient care,
      it is important that this potential complication is recognized and its clinical
      aspects appropriately assessed. The conclusion of the report comprises a concise
      review of the most severe complications in the immediate period after ESWL.

PMID- 15459873
TI  - [Interventional radiologic management for early post-transplant perfusion failure
      of renal allografts].
AB  - PURPOSE: Open surgery for correction of early vascular complications in allogenic
      kidney transplantation carries the risk for increased morbidity and graft loss.
      The question was raised whether modern interventional radiologic techniques,
      especially the use of vascular stents, could play an alternative therapeutic role
      in those complicated cases. MATERIAL AND METHODS: 3 patients with early
      postoperative perfusion failure of their renal grafts were referred to the
      radiologist after Doppler sonography. Immediate digital subtraction angiography
      was initiated and during the same session percutaneous transluminal angiography
      and placement of a vascular stent were performed to treat the vascular lesion.
      Anticoagulation was started with low-dose aspirin 100 mg/day. RESULTS: In all 3
      patients an intimal dissection of the renal artery with formation of a relevant
      stenosis was found. Stenosis was corrected by angioplasty and stenting. In one
      case an accidentally found renal vein thrombosis was additionally treated by
      transcatheter thrombo-aspiration. No complications related to the interventions
      occurred. In 2 patients diuresis returned immediately and renal function remained
      stable in the longterm (follow-up 6 month). In one case massive peripheral
      arterial thrombosis had to be diagnosed in spite of successful recanalization of
      the renal artery. After explantation of the organ histology revealed extended
      parenchymal necrosis. CONCLUSIONS: The timely use of angiography after Doppler
      sonographic diagnosis for renal transplant perfusion failure is of help not only
      for exact diagnosis but also for immediate treatment. Radiologic interventional
      techniques should be regarded as potentially effective and safe for the treatment
      of early vascular complications after renal transplantation.

PMID- 15459874
TI  - [Adaptive immunotherapy of the advanced prostate cancer - cancer testis antigen
      (CTA) as possible target antigens].
AB  - Prostate cancer (PCa) like other tumors expresses antigens that may serve as
      target for specific immunotherapy. Special antigen-presenting cells (e. g.,
      dendritic cells) are capable of generating tumor-specific immunity. Cytotoxic T
      cells (killer cells) are very effective against antigens and, consequently,
      against the respective tissue or tumor. Cancer testis antigens (CTA) are
      expressed in various human cancers but, aside from the testicles, not in normal
      tissue. Therefore, they are suitable for a specific tumor immunotherapy. We
      looked at different CTA (LAGE-1, PRAME, MAGE-C2, NY-ESO-1, SSX-2 and PAGE4) and
      their occurrence in prostatic cancer. Expression of CTA in various PCa cell lines
      and PCa material from patients was very heterogeneous. Only PAGE4 was expressed
      in primary PCa and in LnCaP cells as well as in hormone-dependent and hormone
      refractory PCa probes. We conclude that PAGE4 should be further evaluated as a
      potential target for immunotherapy of PCa.

PMID- 15459875
TI  - [Cyclooxygenase-2-expression in bladder cancer: tumor-biological and clinical
      implications].
AB  - PURPOSE: Cyclooxygenase-2 (Cox-2) contributes to the carcinogenesis of human
      tumors by various mechanisms. As Cox-2-expression has been found in most human
      neoplasms, selective Cox-2-inhibitors could be used as a molecular targeted
      therapy, and first clinical trials have already been initiated. Moreover, Cox-2
      inhibitors have been shown to add to the activity of conventional cytotoxic
      therapies in experimental and clinical studies. We analyzed Cox-2-expression in
      bladder cancer and its implications on clinical parameters. MATERIALS AND
      METHODS: Cox-2-expression was evaluated immunohistochemically in 157 patients
      undergoing radical cystectomy. Sixty-two patients had received cisplatin-based
      treatment during follow-up, either as adjuvant therapy or for metastatic disease.
      Cox-2-expression was correlated with clinical and pathological parameters,
      survival data and outcome of chemotherapy. RESULTS: Cox-2 was expressed in 83.4 %
      of tumors. No association was found with TNM-staging and histological grading,
      but a significant relation to the histologic subtype (transitional vs. squamous
      cell carcinoma, p = 0.038) was present. Survival analysis showed no impact of Cox
      2-expression on overall or disease-free survival. However, a subgroup of
      chemotherapy patients demonstrated a significant correlation of strong Cox-2
      expression with worse overall survival time (p = 0.01). CONCLUSIONS: Cox-2
      expression was found in the majority of invasive bladder tumors. For patients who
      underwent chemotherapy, a significant relation of Cox-2-expression and worse
      overall survival was demonstrated. Cox-2 seems to be an interesting molecular
      target for the diagnosis and therapy of bladder cancer. Further experimental and
      clinical studies are warranted to elucidate whether Cox-2-inhibition can serve as
      an additive therapy to chemotherapy of bladder cancer.

PMID- 15459876
TI  - A test of Simpson's "rule of the survival of the relatively unspecialized" using
      fossil crinoids.
AB  - Temporally long-ranging (=long-lived) taxa have been postulated to have unusual
      properties that aid their prolonged geologic survival. Past studies have examined
      dispersal capabilities, geographic ranges, and single-character morphological
      adaptations as factors that may contribute to geologic longevity. Here, I test
      whether long-lived fossil crinoid taxa are morphologically unusual using a whole
      suite of morphological characters. I define long-lived taxa in several explicit,
      comparative ways. I find that long-lived crinoid genera and families are often
      less distant from mean morphologies of their crinoid orders than their shorter
      lived relatives; that is, they are relatively less specialized. I also compare
      the morphology of crinoid genera relative to basal members of their respective
      orders; mean morphological distances of long-lived genera from basal morphologies
      are seldom distinct from those of their shorter-lived relatives. I observe that
      long-lived crinoid genera are less distant from mean morphologies of their
      temporal cohorts compared with shorter-lived genera but not in a statistically
      significant manner. I conclude that long-lived crinoids are relatively
      unspecialized, in the sense that they are relatively closer to mean morphologies
      of their taxonomic groups.

PMID- 15459877
TI  - Molecular parentage analysis in experimental newt populations: the response of
      mating system measures to variation in the operational sex ratio.
AB  - Molecular studies of parentage have been extremely influential in the study of
      sexual selection in the last decade, but a consensus statistical method for the
      characterization of genetic mating systems has not yet emerged. Here we study the
      utility of alternative mating system measures by experimentally altering the
      intensity of sexual selection in laboratory-based breeding populations of the
      rough-skinned newt. Our experiment involved skewed sex ratio (high sexual
      selection) and even sex ratio (low sexual selection) treatments, and we assessed
      the mating system by assigning parentage with microsatellite markers. Our results
      show that mating system measures based on Bateman's principles accurately reflect
      the intensity of sexual selection. One key component of this way of quantifying
      mating systems is the Bateman gradient, which is currently underutilized in the
      study of genetic mating systems. We also compare inferences based on Bateman's
      principles with those obtained using two other mating system measures that have
      been advocated recently (Morisita's index and the index of resource
      monopolization), and our results produce no justification for the use of these
      alternative measures. Overall, our results show that Bateman's principles provide
      the best available method for the statistical characterization of mating systems
      in nature.

PMID- 15459878
TI  - Infertile matings and sperm competition: the effect of "nonsperm representation"
      on intraspecific variation in sperm precedence patterns.
AB  - In theoretical and experimental approaches to the study of sperm competition, it
      is often assumed that ejaculates always contain enough sperm of good quality and
      that they are successfully transferred and used for fertilization. However, this
      view neglects the potential effects of infertility and sperm limitation.
      Permanent or temporal male infertility due to male sterility, insemination
      failures, or failures to fertilize the ova implies that some males do not achieve
      sperm representation in the female reproductive tract after mating. A review of
      the literature suggests that rates of nonsperm representation may be high; values
      for the proportion of infertile matings across 30 insect species vary between 0%
      and 63%, with the median being 22%. I simulated P2 (the proportion of offspring
      fathered by the second male to copulate with a female in a double-mating trial)
      distributions under a mechanism of random sperm mixing when sample sizes and
      rates of male infertility varied. The results show that nonsperm representation
      can be responsible for high intraspecific variance in sperm precedence patterns
      and that it can generate misleading interpretations about the mechanism of sperm
      competition. Nonsperm representation might be a common obstacle in the studies of
      sperm competition and postcopulatory female choice.

PMID- 15459879
TI  - Ideal free distributions, evolutionary games, and population dynamics in multiple
      species environments.
AB  - In this article, we develop population game theory, a theory that combines the
      dynamics of animal behavior with population dynamics. In particular, we study
      interaction and distribution of two species in a two-patch environment assuming
      that individuals behave adaptively (i.e., they maximize Darwinian fitness).
      Either the two species are competing for resources or they are in a predator-prey
      relationship. Using some recent advances in evolutionary game theory, we extend
      the classical ideal free distribution (IFD) concept for single species to two
      interacting species. We study population dynamical consequences of two-species
      IFD by comparing two systems: one where individuals cannot migrate between
      habitats and one where migration is possible. For single species, predator-prey
      interactions, and competing species, we show that these two types of behavior
      lead to the same population equilibria and corresponding species spatial
      distributions, provided interspecific competition is patch independent. However,
      if differences between patches are such that competition is patch dependent, then
      our predictions strongly depend on whether animals can migrate or not. In
      particular, we show that when species are settled at their equilibrium population
      densities in both habitats in the environment where migration between habitats is
      blocked, then the corresponding species spatial distribution need not be an IFD.
      Thus, when species are given the opportunity to migrate, they will redistribute
      to reach an IFD (e.g., under which the two species can completely segregate), and
      this redistribution will also influence species population equilibrial densities.
      Alternatively, we also show that when two species are distributed according to
      the IFD, the corresponding population equilibrium can be unstable.

PMID- 15459880
TI  - Androgens and the immunocompetence handicap hypothesis: unraveling direct and
      indirect pathways of immunosuppression in song sparrows.
AB  - The immunocompetence handicap hypothesis proposes that testosterone (T)-dependent
      sexual signals are honest indicators of male health or genetic quality because
      only high-quality males are able to withstand the obligate effects of T-induced
      immunosuppression. In birds, the basic assumption that T suppresses immune
      function is equivocal, and the physiological mechanisms underlying T-induced
      immunosuppression remain to be investigated. We explored the proximate pathways
      of T-induced immunosuppression in song sparrows (Melospiza melodia) by treating
      captive nonbreeding males with different androgens and measuring several
      components of acquired immune function. Males implanted with T suppressed cell
      mediated and humoral immune responses compared to males implanted with 5alpha
      dihydrotestosterone (DHT), dehydroepiandrosterone, or control (empty) implants.
      Furthermore, T treatment increased plasma levels of corticosterone and decreased
      body mass and fat stores in relation to other treatments. The failure of DHT to
      depress immune function suggests that T-induced immunosuppression does not occur
      through a direct pathway because both T and DHT bind to androgen receptors on
      target cells. Instead, we outline indirect pathways that are likely responsible
      for suppression of the avian immune system that include stress-induced
      immunosuppression, aromatization to estrogen, and alterations in energy
      allocation that constrain expenditures toward immune system activation.

PMID- 15459881
TI  - Ectoparasitic "jacks-of-all-trades": relationship between abundance and host
      specificity in fleas (Siphonaptera) parasitic on small mammals.
AB  - Animal species with larger local populations tend to be widespread across many
      localities, whereas species with smaller local populations occur in fewer
      localities. This pattern is well documented for free-living species and can be
      explained by the resource breadth hypothesis: the attributes that enable a
      species to exploit a diversity of resources allow it to attain a broad
      distribution and high local density. In contrast, for parasitic organisms, the
      trade-off hypothesis predicts that parasites exploiting many host species will
      achieve lower mean abundance on those hosts than more host-specific parasites
      because of the costs of adaptations against multiple defense systems. We test
      these alternative hypotheses with data on host specificity and abundance of fleas
      parasitic on small mammals from 20 different regions. Our analyses controlled for
      phylogenetic influences, differences in host body surface area, and sampling
      effort. In most regions, we found significant positive relationships between flea
      abundance and either the number of host species they exploited or the average
      taxonomic distance among those host species. This was true whether we used mean
      flea abundance or the maximum abundance they achieved on their optimal host.
      Although fleas tended to exploit more host species in regions with either larger
      number of available hosts or more taxonomically diverse host faunas, differences
      in host faunas between regions had no clear effect on the abundance-host
      specificity relationship. Overall, the results support the resource breadth
      hypothesis: fleas exploiting many host species or taxonomically unrelated hosts
      achieve higher abundance than specialist fleas. We conclude that generalist
      parasites achieve higher abundance because of a combination of resource
      availability and stability.

PMID- 15459882
TI  - The evolution of paternal care with overlapping broods.
AB  - Most attempts to model the evolution of parental care assume that caring and
      mating are mutually exclusive activities (i.e., individuals acquire and guard
      broods "sequentially"). However, in most fish and certain insects, males can keep
      mating and collecting additional eggs while continuing to guard broods obtained
      earlier (i.e., males guard "overlapping" broods). We present a model of parental
      care with overlapping broods in which males can mate and guard simultaneously,
      even though there is a trade-off between these two activities. Within this
      framework, we show that male care is favored by short female processing times and
      high population densities, which minimize the mating cost of care. Relatively low
      mortality while guarding is also important for the stability of male care. Female
      care, on the other hand, is favored by long female processing times and low
      populations densities, which lead to longer intermating intervals. Biparental
      care is stable only when the cost to benefit ratio of care was not biased toward
      either sex. We derive quantitative estimates of fitness for different strategies
      for two species of assassin bugs with male and female uniparental care and show
      that the model predicts the correct form of care for both species. We believe our
      model might help explain the prevalence of male uniparental care in certain taxa,
      such as fish.

PMID- 15459883
TI  - Adaptive phenotypic plasticity and the successful colonization of a novel
      environment.
AB  - Behavior and other forms of phenotypic plasticity potentially enable individuals
      to deal with novel situations. This implies that establishment of a population in
      a new environment is aided by plastic responses, as first suggested by Baldwin
      (1896). In the early 1980s, a small population of dark-eyed juncos from a
      temperate, montane environment became established in a Mediterranean climate in
      coastal San Diego. The breeding season of coastal juncos is more than twice as
      long as that of the ancestral population, and they fledge approximately twice as
      many young. We investigated the adaptive significance of the longer breeding
      season and its consequences for population persistence. Within the coastal
      population, individuals with longer breeding seasons have higher offspring
      production and recruitment, with no measured detrimental effects such as higher
      mortality or lower reproductive success the following year. Population size has
      remained approximately constant during the 6 years of study (1998-2003). The
      increase in reproductive effort in the coastal population contributes
      substantially to the persistence of this population because there is no evidence
      of density-dependent recruitment, which would otherwise negate the effects of
      increased fledgling production. These results provide the first quantitative
      support of Baldwin's proposition that plasticity can be crucial for population
      persistence during the early stages of colonization.

PMID- 15459884
TI  - The dynamical consequences of developmental variability and demographic
      stochasticity for host-parasitoid interactions.
AB  - Few age-structured models of species dynamics incorporate variability and
      uncertainty in population processes. Motivated by laboratory data for an insect
      and its parasitoid, we investigate whether such assumptions are appropriate when
      considering the population dynamics of a single species and its interaction with
      a natural enemy. Specifically, we examine the effects of developmental
      variability and demographic stochasticity on different types of cyclic dynamics
      predicted by traditional models. We show that predictions based on the
      deterministic fixed-development approach are differentially sensitive to
      variability and noise in key life stages. In particular, we find that the
      demonstration of half-generation cycles in the single-species model and the
      multigeneration cycles in the host-parasitoid model are sensitive to the
      introduction of developmental variability and noise, whereas generation cycles
      are robust to the intrinsic variability and uncertainty that may be found in
      nature.

PMID- 15459885
TI  - Time constraints decouple age and size at maturity and physiological traits.
AB  - Life-history theory predicts changes in age and size at maturity in response to
      constraints in animals with complex life cycles. A critical underlying assumption
      is that only these traits are optimized during ontogeny. However, it is not clear
      how altered life histories mechanistically translate into survival and fecundity.
      Here we present data from damselflies reared from egg to adult under day lengths
      mimicking the start or end (time constrained) of the season at high and low food
      level. These data show that an important component of immunity is suppressed
      under time-constrained development as well as under low food conditions and that
      fat storage is affected only by food availability. Intriguingly, the
      physiological responses are partly decoupled from age and size at maturity, which
      indicates that the predictive value of traits such as age and size at maturity
      might well be restricted.

PMID- 15459886
TI  - Sexual selection: harem size and the variance in male reproductive success.
AB  - Sexual selection is potentially stronger than natural selection when the variance
      in male reproductive fitness exceeds all other components of fitness variance
      combined. However, measuring the variance in male reproductive fitness is
      difficult when nonmating males are absent, inconspicuous, or otherwise difficult
      to find. Omitting the nonmating males inflates estimates of average male
      reproductive success and diminishes the variance, leading to underestimates of
      the potential strength of sexual selection. We show that, in theory, the
      proportion of the total variance in male fitness owing to sexual selection is
      approximately equal to H, the mean harem size, as long as H is large and females
      are randomly distributed across mating males (i.e., Vharem=H). In this case, mean
      harem size not only provides an easy way to estimate the potential strength of
      sexual selection but also equals the opportunity for sexual selection, I(mates).
      In nature, however, females may be overdispersed with Vharem<H or more aggregated
      than random with Vharem>H. We show that H+(k-1) is a good measure of the
      opportunity for sexual selection, where k is the ratio Vharem/H. A review of
      mating system data reveals that in nature the median ratio for Vharem/H is 1.04,
      but as H increases, females tend to become more aggregated across mating males
      with V(harem) two to three times larger than H.

PMID- 15459887
TI  - Concurrent evolution of resistance and tolerance to pathogens.
AB  - Recent experiments on plant defenses against pathogens or herbivores have shown
      various patterns of the association between resistance, which reduces the
      probability of being infected or attacked, and tolerance, which reduces the loss
      of fitness caused by the infection or attack. Our study describes the
      simultaneous evolution of these two strategies of defense in a population of
      hosts submitted to a pathogen. We extended previous approaches by assuming that
      the two traits are independent (e.g., determined by two unlinked genes), by
      modeling different shapes of the costs of defenses, and by taking into account
      the demographic and epidemiological dynamics of the system. We provide novel
      predictions on the variability and the evolution of defenses. First, resistance
      and tolerance do not necessarily exclude each other; second, they should respond
      in different ways to changes in parameters that affect the epidemiology or the
      relative costs and benefits of defenses; and third, when comparing investments in
      defenses among different environments, the apparent associations among
      resistance, tolerance, and fecundity in the absence of parasites can lead to the
      false conclusion that only one defense trait is costly. The latter result
      emphasizes the problems of estimating trade-offs and costs among natural
      populations without knowledge of the underlying mechanisms.

PMID- 15459888
TI  - Habitat selection and population regulation in temporally fluctuating
      environments.
AB  - Understanding and predicting the distribution of organisms in heterogeneous
      environments lies at the heart of ecology, and the theory of density-dependent
      habitat selection (DDHS) provides ecologists with an inferential framework
      linking evolution and population dynamics. Current theory does not allow for
      temporal variation in habitat quality, a serious limitation when confronted with
      real ecological systems. We develop both a stochastic equivalent of the ideal
      free distribution to study how spatial patterns of habitat use depend on the
      magnitude and spatial correlation of environmental stochasticity and also a
      stochastic habitat selection rule. The emerging patterns are confronted with
      deterministic predictions based on isodar analysis, an established empirical
      approach to the analysis of habitat selection patterns. Our simulations highlight
      some consistent patterns of habitat use, indicating that it is possible to make
      inferences about the habitat selection process based on observed patterns of
      habitat use. However, isodar analysis gives results that are contingent on the
      magnitude and spatial correlation of environmental stochasticity. Hence, DDHS is
      better revealed by a measure of habitat selectivity than by empirical isodars.
      The detection of DDHS is but a small component of isodar theory, which remains an
      important conceptual framework for linking evolutionary strategies in behavior
      and population dynamics.

PMID- 15459889
TI  - Functional characterization of human organic cation transporter OCTN1 single
      nucleotide polymorphisms in the Japanese population.
AB  - The organic cation transporter OCTN1 (SLC22A4) is expressed ubiquitously, with
      strong expression in kidney, trachea, bone marrow, and fetal liver, and it
      mediates transport of organic cations in a pH-dependent manner. Recent studies
      have identified single nucleotide polymorphisms (SNPs) of OCTN1 in the Japanese
      population. Two SNPs present in the exon regions, c1063t and g1531a, cause amino
      acid mutation, Thr306Ile (T306I) and Gly462Glu (G462E), respectively. We examined
      the influence of these SNPs on the intracellular localization, protein
      expression, and transport activity of OCTN1. Immunocytochemical analysis showed
      similar localizations of OCTN1 in cellular membranes of HEK293 cells transiently
      transfected with an expression plasmid DNA for OCTN1 or its SNP allelic variants.
      The Km and Vmax values for tetraethylammonium (TEA) uptake by T306I were similar
      to those of the wild-type even when the Vmax value was normalized for the
      expression level of OCTN1 protein. In contrast, G462E had almost negligible
      transport activity, although the protein expression level of G462E was equivalent
      to that of the wild-type. We conclude that the SNP that causes the single amino
      acid mutation T306I does not affect TEA transport activity, whereas the mutation
      G462E abrogates the TEA transport activity, presumably affecting the
      physiological function of OCTN1 and/or the pharmacological characteristics of its
      substrates.

PMID- 15459890
TI  - Frog intestinal sac: a new in vitro method for the assessment of intestinal
      permeability.
AB  - The aim of this study was to evaluate a new experimental protocol utilizing
      isolated frog intestinal sacs for the assessment of intestinal drug permeability
      in humans. Segments of approximately 5.0 cm in length were used for these
      experiments. The intestinal sacs were filled with a solution of the appropriate
      drug in frog Ringer (FR) and immersed in a vial containing fresh FR. The
      transport was monitored for a period ranging from 2 to 5 h by moving the
      intestinal sac at each time point to a new vial containing fresh medium (Method
      A). Alternatively, according to Method B, at predetermined times aliquots of
      receiving mixture were taken up without removing the intestinal sac, and replaced
      with fresh drug-free FR. In all cases, the samples were analyzed by HPLC. A
      series of 20 noncongeneric drugs, predominantly absorbed by passive diffusion
      mechanism, was examined. The results indicate that drugs completely absorbed in
      humans had Papp values greater than 1 x 10(-6) cm/s, while drugs absorbed <90%
      had Papp values lower than 1 x 10(-6) cm/s. By plotting Log Papp values against
      percent human absorption, an approximately sigmoidal relationship was obtained.
      The frog intestinal sac method was evaluated as a permeability model to classify
      the 20 studied drugs into the Biopharmaceutics Classification System (BCS). By
      comparing the predictions made by this new approach with those reported in
      literature, it can be concluded that a satisfactory biopharmaceutical
      classification may be based on the Papp values determined by the frog intestinal
      permeability. Molecular properties relevant to passive intestinal permeability
      were considered to evaluate the correlation with the frog intestinal permeability
      rates recorded. Good relationships were observed when hydrogen-bonding parameters
      were expressed as a function of the Log Papp values. It can be concluded that the
      in vitro permeability coefficient deduced from isolated frog intestinal
      experiments can be used for predicting peroral absorption in humans for passively
      absorbed compounds. Computational methods for prediction of frog intestinal
      permeability may be applied in a highly simplified manner.

PMID- 15459891
TI  - Quantitative study of electrophoretic and electroosmotic enhancement during
      alternating current iontophoresis across synthetic membranes.
AB  - One of the primary safety and tolerability limitations of direct current
      iontophoresis is the potential for electrochemical burns associated with the
      necessary current densities and/or application times required for effective
      treatment. Alternating current (AC) transdermal iontophoresis has the potential
      to eliminate electrochemical burns that are frequently observed during direct
      current transdermal iontophoresis. Although it has been demonstrated that the
      intrinsic permeability of skin can be increased by applying low-to-moderate AC
      voltages, transdermal transport phenomena and enhancement under AC conditions
      have not been systematically studied and are not well understood. The aim of the
      present work was to study the fundamental transport mechanisms of square-wave AC
      iontophoresis using a synthetic membrane system. The model synthetic membrane
      used was a composite Nuclepore membrane. AC frequencies ranging from 20 to 1000
      Hz and AC fields ranging from 0.25 to 0.5 V/membrane were investigated. A charged
      permeant, tetraethyl ammonium, and a neutral permeant, arabinose, were used. The
      transport studies showed that flux was enhanced by increasing the AC voltage and
      decreasing AC frequency. Two theoretical transport models were developed: one is
      a homogeneous membrane model; the other is a heterogeneous membrane model.
      Experimental transport data were compared with computer simulations based on
      these models. Excellent agreement between model predictions and experimental data
      was observed when the data were compared with the simulations from the
      heterogeneous membrane model.

PMID- 15459892
TI  - Responses of temporal retinal growth cones to ephrinA5-coated beads.
AB  - The topographic positioning of retinal axons in the optic tectum is regulated, at
      least in part, by ephrinA/EphA repulsive interactions. Temporal axons, expressing
      high levels of EphA receptors, project to the ephrinA5-poor anterior tectum and
      avoid the ephrinA5-rich posterior tectum. To examine the dynamic behavior of
      temporal growth cones when they first encounter ephrinA, we manipulated ephrinA
      coated beads with a laser tweezer into desired positions around the growth cones
      of chick retinal axons in culture. At high concentrations of ephrinA5 on the
      beads, growth cones typically collapsed on contacting the bead. At low
      concentrations, however, growth cones showed heterogeneous responses with some
      growth cones showing repulsive turning and others showing attractive turning
      after contacting the bead. Experiments with two beads indicate that retinal axons
      integrate guidance information that is provided simultaneously at two discrete
      locations. When a time-delay was introduced between exposure to the first and the
      second bead, individual axons exhibited a stereotyped response to the repeated
      stimuli, either responding with attraction followed by attraction, or showing
      repulsion followed by repulsion or collapse. Our results suggest the existence of
      at least two retinal subpopulations from the temporal retina, one being
      attracted, another being repelled by low levels of ephrinA5. These findings
      demonstrate that temporal retinal axons are not universally repelled by ephrinA5
      and suggest that their ability to respond differentially to low concentrations
      may help them to map in a continuous manner over the surface of the anterior
      tectum.

PMID- 15459893
TI  - Increased microglial activation and astrogliosis after intranasal administration
      of kainic acid in C57BL/6 mice.
AB  - Glutamate excitotoxicity plays a key role in inducing neuronal cell death in many
      neurological diseases. In mice, intranasal administration of kainic acid (KA), an
      analogue of the excitotoxin glutamate, results in hippocampal cell death and
      provides a well-characterized model for studies of human neurodegenerative
      diseases. In this study, we describe neurodegeneration and gliosis following
      intranasal administration of KA in C57BL/6 mice. By using Nissl's staining,
      neurodegeneration was found in area CA3 of hippocampus, and neuronal apoptosis
      was demonstrated by enhanced FAS(CD95/APO-1) expression detected by
      immunohistochemistry and Western blotting. Astrogliosis was exhibited by
      increased glial fibrillary acidic protein (GFAP) expression in the hippocampus
      and cortex. We also studied the profile of molecular expression on microglia in
      C57BL/6 mice. One and 3 days after KA administration, CD45, F4/80, CD86, MHCII,
      iNOS but not CD40 expression was enhanced or induced on microglia. In summary, KA
      administration results in an early microglial activation and a prolonged
      astrogliosis in C57BL/6 mice.

PMID- 15459894
TI  - Differential properties of dentate gyrus and CA1 neural precursors.
AB  - In the present article we investigated the properties of CA1 and dentate gyrus
      cell precursors in adult rodents both in vivo and in vitro. Cell proliferation in
      situ was investigated by rating the number of cells incorporating BrdU after
      kainate-induced seizures. CA1 precursors displayed a greater proliferation
      capacity than dentate gyrus precursors. The majority of BrdU-labeled cells in CA1
      expressed Nestin and Mash-1, two markers of neural precursors. BrdU-positive
      cells in the dentate gyrus expressed Nestin, but only a few expressed Mash-1. In
      animals pretreated with the antimitotic azacytidine, the capacity of kainate to
      enhance the proliferation was higher in CA1 than in the dentate gyrus.
      Differences in intrinsic progenitor cell activity could underlie these different
      expansion capacities. Thus, we compared the renewal- expansion and multipotency
      of dentate gyrus and CA1 precursors isolated in vitro. We found that the
      dissected CA1 region, including the periventricular zone, is enriched in
      neurosphere-forming cells (presumed stem cells), which respond to either EGF or
      FGF-2. Dentate gyrus contains fewer neurosphere-forming cells and none that
      respond to FGF-2 alone. Neurospheres generated from CA1 were multipotent and
      produced neurons, astrocytes, and oligodendrocytes, while dentate gyrus
      neurospheres mostly produced glial cells. The analysis of the effects of EGF on
      organotypic cultures of hippocampal slices depicted similar features: BrdU and
      Nestin immunoreactivities increased after EGF treatment in CA1 but not in the
      dentate gyrus. These results suggest that CA1 precursors are more stem-cell-like
      than granule cell precursors, which may represent a more restricted precursor
      cell.

PMID- 15459895
TI  - Neural song preference during vocal learning in the zebra finch depends on age
      and state.
AB  - The zebra finch acquires its song by first memorizing a model song from a tutor
      and then matching its own vocalizations to the memory trace of the tutor song,
      called a template. Neural mechanisms underlying this process require a link
      between the neural memory trace and the premotor song circuitry, which drives
      singing. We now report that a premotor song nucleus responds more to the tutor
      song model than to every other stimulus examined, including the bird's own song
      (BOS). Neural tuning to the song model occurred only during waking and peaked
      during the template-matching period of development, when the vocal motor output
      is sculpted to match the tutor song. During the same developmental phase, the BOS
      was the most effective excitatory stimulus during sleep. The preference for BOS
      compared to tutor song inverted with sleep/wake state. Thus, song preference
      shifts with development and state.

PMID- 15459896
TI  - Expression of a dominant negative form of Daxx in vivo rescues motoneurons from
      Fas (CD95)-induced cell death.
AB  - Fas-induced death of motoneurons in vitro has been shown to involve two signaling
      cascades that act together to execute the death program: a Fas-Daxx-ASK-1-p38
      kinase-nNOS branch, which controls transcriptional and post-translational events,
      and the second classical Fas-FADD-caspase-8 branch. To analyze the role of Daxx
      in the developmental motoneuron cell death, we studied Fas-dependent cell death
      in motoneurons from transgenic mice that overexpress a dominant-negative form of
      Daxx. Motoneurons purified from these transgenic mice are resistant to Fas
      induced death. This protective effect is specific to Fas because ultraviolet
      irradiation-triggered death is not affected by the transgene. The Daxx and the
      FADD pathways work in parallel because only Daxx, but not FADD, is involved in
      the transcriptional control of neuronal nitric oxide synthase and nitric oxide
      production. Nevertheless, we do not observe involvement of Daxx in developmental
      motoneuronal cell death, as the pattern of naturally occurring programmed cell
      death in vivo is normal in transgenic mice overexpressing the dominant negative
      form of Daxx, suggesting that Daxx-independent pathways are used during
      development.

PMID- 15459897
TI  - Dose and age-dependent axonal responses of embryonic trigeminal neurons to
      localized NGF via p75NTR receptor.
AB  - Nerve growth factor (NGF) and related neurotrophins are target-derived survival
      factors for sensory neurons. In addition, these peptides modulate neuronal
      differentiation, axon guidance, and synaptic plasticity. We tested axonal
      behavior of embryonic trigeminal neurons towards localized sources of NGF in
      collagen gel assays. Trigeminal axons preferentially grow towards lower doses of
      localized NGF and grow away from higher concentrations at earlier stages of
      development, but do not show this response later. Dorsal root ganglion axons also
      show similar responses to NGF, but NGF-dependent superior cervical ganglion axons
      do not. Such axonal responses to localized NGF sources were also observed in Bax
      /- mice, suggesting that the axonal effects are largely independent of cell
      survival. Immunocytochemical studies indicated that axons, which grow towards or
      away from localized NGF are TrkA-positive, and TrkA-/- TG axons do not respond to
      any dose of NGF. We further show that axonal responses to NGF are absent in TG
      derived from mice that lack the p75 neurotrophin receptor (p75NTR). Collectively,
      our results suggest that localized sources of NGF can direct axon outgrowth from
      trigeminal ganglion in a dose- and age-dependent fashion, mediated by p75NTR
      signaling through TrkA expressing axons.

PMID- 15459898
TI  - Opsonization of polyethylene wear particles regulates macrophage and osteoblast
      responses in vitro.
AB  - The cellular reaction to wear debris may result in the failure of an artificial
      joint's fixation to the skeleton. The influence of debris opsinization on cell
      activity has received little attention. This study seeks to establish whether
      different proteinaceous culture environments may invoke variant cellular
      responses to debris challenge. Consideration of the zeta potential of a low
      density polyethylene particle group and an ex vitro ultrahigh molecular weight
      polyethylene particle group revealed that the nature of the protein adsorbants is
      related to the concentration of the proteins in solution. Furthermore, the
      composition of the adsorbed layer was shown to vary with the spectra of proteins
      in solution. In standard cell culture conditions zeta potential approached zero,
      indicating the high probability of particle agglomeration. Cell challenge studies
      with U937 macrophages showed that BSA and FCS protein adsorption mediated
      increased cell adhesion, while bovine IgG showed little change over control
      values. No changes in behavior of osteoblastic cells were observed in similar
      experiments.

PMID- 15459899
TI  - Dynamic mechanical analysis of viscoelastic functions in packable composite
      resins measured by torsional resonance.
AB  - The objective of this study was to evaluate the viscoelastic functions of
      packable composite resins with the use of a resonant dynamic mechanical analysis
      technique in torsion. The materials tested were: Alert (Jeneric Pentron), Prodigy
      Condensable (Kerr Corporation), Surefil (Dentsply DeTrey), and Filtek P60 (3M
      Dental Products). Dynamic torsional loading was conducted in the frequency range
      from 1 to 150 Hz. Composite specimens were tested after storage in water at 37
      degrees C for 24 h. One group was thermal cycled for 3000 cycles with
      temperatures of 5-37-50 degrees C. Measurements were taken at 21 degrees C dry,
      and at 37 and 50 degrees C wet. Storage modulus, loss tangent, and other
      viscoelastic parameters were determined from the amplitude/frequency curves. Data
      for storage modulus and loss tangent of the materials were analyzed by means of
      ANOVA and Student-Newman-Keuls test (alpha = 0.05). It was found that there were
      significant differences (P < 0.001) in storage modulus and loss tangent among the
      packable composites tested. The highest value of storage modulus, in measurements
      at 21 degrees C, was for Alert (10.3 GPa), followed by Filtek P60 (9.31 GPa),
      Surefil (7.29 GPa), and Prodigy Condensable (6.74 GPa). There were significant
      differences (P < 0.001) in storage modulus and loss tangent among the four
      different conditions tested. Storage modulus decreased at higher temperatures,
      whereas the loss tangent increased. Thermal cycling increased storage modulus and
      decreased loss tangent. The results showed that both monomer and filler
      composition and filler loading of the materials significantly affect their
      viscoelastic functions, and the mechanical properties of the products cannot be
      characterized from the packability alone.

PMID- 15459900
TI  - The imbalance between Bim and Mcl-1 expression controls the survival of human
      myeloma cells.
AB  - Multiple myeloma is a fatal B cell malignancy characterized by the accumulation
      of plasma cells within the bone marrow. IL-6 is a major survival factor for
      myeloma cells. Bcl-2 protein family regulates pathways to apoptosis that are
      activated upon growth factor deprivation. Pro-apoptotic proteins that have only a
      single Bcl-2 homology domain, BH3-only, are potent inducers of apoptosis. In
      myeloma cells, Mcl-1 has been shown to be a major anti-apoptotic protein that
      appears to regulate cell survival through the JAK/STAT pathway. In this study, we
      examined the regulation of the BH3-only protein Bim and its interaction with Mcl
      1. The three major Bim isoforms are expressed in myeloma cells and are negatively
      regulated by IL-6. Blockade of IL-6 signaling induces an up-regulation of Bim
      concomitant to Mcl-1 down-regulation. Of major interest, Bim is found strongly
      associated with Mcl-1 in viable myeloma cells while this interaction is disrupted
      under apoptosis induction. Of note, while Bim is also found strongly associated
      to Bcl-2, this interaction is not changed under apoptosis induction. Thus, in
      myeloma cells, Mcl-1 neutralizes Bim through complex formation and therefore
      prevents apoptosis. Under apoptosis induction, the disappearance of Mcl-1 allows
      Bim to exercise its pro-apoptotic function and to activate Bax.

PMID- 15459901
TI  - Parenteral exposure to high HIV viremia leads to virus-specific T cell priming
      without evidence of infection.
AB  - Previous studies on CTL responses in HIV-exposed uninfected individuals assumed
      that the patients were exposed to replicating HIV, but the possibility that the
      immune responses detected were primed by exposure to a defective virus or viral
      antigen could not be excluded. Epidemiological and laboratory analysis of a
      nosocomial outbreak of acute hepatitis B unequivocally allowed the identification
      of an HIV-1- and HBV-co-infected patient with high plasma levels of both viruses,
      as the source case of the epidemics. This clinical setting provided a natural
      model for testing the HIV-specific T cell response in patients exposed to blood
      from a patient with highly replicating HIV. Parenteral exposure to both viruses
      led to acute hepatitis B in five subjects without evidence of HIV-1 infection.
      Cryopreserved lymphocytes derived from three exposed patients were tested ex vivo
      in an ELISPOT assay for IFN-gamma release upon stimulation with peptides from
      structural and non-structural HIV proteins; one of the patients was also tested
      with four HLA/class I tetramers. Circulating HIV-specific CD8 cells were detected
      by tetramer staining and a high frequency of T cells were able to release IFN
      gamma upon stimulation with HIV peptides, showing in vivo T cell priming by HIV.
      These results unequivocally demonstrate a HIV-specific cell-mediated immune
      response in the absence of infection after exposure to highly replicating HIV.

PMID- 15459902
TI  - Expression of the SH2D1A gene is regulated by a combination of transcriptional
      and post-transcriptional mechanisms.
AB  - The SH2D1A gene, which is altered or deleted in patients with X-linked
      lymphoproliferative disease, encodes the small protein SAP (for SLAM-associated
      protein) that is expressed in T and NK cells. A 22-bp fragment in close proximity
      to an initiator-like site was defined as the basal promoter of mouse SH2D1A, and
      a highly homologous 33-bp segment was defined as the human basal promoter. When
      an Ets consensus site was mutated, no reporter activity was detectable. Gel
      mobility supershift assays revealed that the two transcription factors Ets-1 and
      Ets-2 bind to the human and mouse sequences. The involvement of Ets-1 and Ets-2
      in expression of SH2D1A was functionally confirmed by overexpression studies of
      their dominant-negative forms. We also found that SH2D1A mRNA decays very rapidly
      in mouse T cells, and its 3' untranslated region (UTR) has RNA-destabilizing
      activity in transfection studies with reporter/3' UTR constructs. As judged by
      RNA-gel mobility shift assays, this rapid degradation of SH2D1A mRNA was due to a
      balance in binding of the factors AUF1 and HuR to its 3' UTR. Although the SH2D1A
      mRNA level decreased upon triggering of the T cell receptor (TCR), the RNA
      degradation rate itself was not altered by TCR engagement.

PMID- 15459903
TI  - Uptake of membrane molecules from T cells endows antigen-presenting cells with
      novel functional properties.
AB  - Although intercellular transfer of cell surface molecules has been observed
      between several cells of the immune system, the physiological relevance of this
      phenomenon remained obscure. Until now the transfer of molecules between antigen
      presenting cells (APC) and T cells has been described as a unidirectional process
      from APC to T cells. However, here we show that T cells in turn donate molecules
      to APC, and that T cell-derived vesicles can mediate this transfer. The
      transferred proteins are incorporated into the APC as active molecules. Our data
      provide evidence that T cells use intercellular molecule transfer to mediate cell
      contact-dependent regulation of T cell responses via modulation of the APC.

PMID- 15459904
TI  - Effect of feed and bleed rate on hybridoma cells in an acoustic perfusion
      bioreactor: part I. Cell density, viability, and cell-cycle distribution.
AB  - For the development of optimal perfusion processes the effect of the feed and
      bleed rate on cell growth in a perfusion bioreactor was studied. The viable-cell
      density, viability, growth, death, and lysis rate and cell-cycle distribution of
      a hybridoma cell line producing an IgG1 were studied over a range of specific
      feed and bleed rates. It was found that the feed and bleed rates applied in the
      different cultures could be divided into two regions based on the viable-cell
      density and cell-cycle distribution. The cultures in the first region, low feed
      rates (0.5 and 1.0 d(-1)) combined with low bleed rates (0.05 and 0.10 d(-1)),
      were nutrient-limited, as an increase in the feed rate resulted in an increase in
      the viable-cell density. The cultures in the second region, high feed and bleed
      rates, were nonnutrient-limited. In this region the viable-cell density decreased
      more or less linearly with an increase in the bleed rate and was independent of
      the feed rate. This suggests that the cells were limited by a cell-related
      factor. Comparison of Trypan-blue dye-exclusion measurements and lactate
      dehydrogenase activity measurements revealed that cell lysis was not negligible
      in this bioreactor set-up. Therefore, lactate-dehydrogenase activity measurements
      were essential to measure the death rate accurately. The specific growth rate was
      nearly constant for all tested conditions. The viability increased with an
      increase of the bleed rate and was independent of the feed rate. Furthermore, the
      specific productivity of monoclonal antibody was constant under all tested
      conditions. For the optimal design of a perfusion process it should first be
      established whether viability is an important parameter. If not, a bleed rate as
      low as possible should be chosen. If low viabilities are to be avoided, the bleed
      rate chosen should be higher, with the value depending on the desired viability.
      Next, the feed rate should be set at such a rate that the cells are just in the
      nonnutrient-limited region.

PMID- 15459905
TI  - Microplate-based filter paper assay to measure total cellulase activity.
AB  - The standard filter paper assay (FPA) published by the International Union of
      Pure and Applied Chemistry (IUPAC) is widely used to determine total cellulase
      activity. However, the IUPAC method is not suitable for the parallel analyses of
      large sample numbers. We describe here a microplate-based method for assaying
      large sample numbers. To achieve this, we reduced the enzymatic reaction volume
      to 60 microl from the 1.5 ml used in the IUPAC method. The modified 60-microl
      format FPA can be carried out in 96-well assay plates. Statistical analyses
      showed that the cellulase activities of commercial cellulases from Trichoderma
      reesei and Aspergillus species determined with our 60-microl format FPA were not
      significantly different from the activities measured with the standard FPA. Our
      results also indicate that the 60-microl format FPA is quantitative and highly
      reproducible. Moreover, the addition of excess beta-glucosidase increased the
      sensitivity of the assay by up to 60%.

PMID- 15459906
TI  - Bacterial P450-catalyzed polyketide hydroxylation on a microfluidic platform.
AB  - The incorporation of a multicomponent, cofactor-dependant P450 into a
      microfluidic biochip is demonstrated. The PikC hydroxylase Streptomyces
      venezuelae was incorporated into a PDMS-based microfluidic channel. The enzyme
      was immobilized to Ni-NTA agarose beads via in situ attachment following the
      addition of the beads to the microchannel. The enzyme loading was approximately 6
      microg per mg of beads resulting in a microchannel loading of 10.7 mg/mL. This
      high enzyme loading enabled the rapid hydroxylation of the macrolide YC-17 to
      methymycin and neomethymycin in about equal amounts with a conversion of >90% at
      a flow rate of 70 nL/min. This high reactivity allowed rapid hydroxylation
      reactions to be performed with short residence times, which is critical for
      complex enzymes with limited inherent stability.

PMID- 15459907
TI  - Monitoring the biological activity of the composting process: Oxygen uptake rate
      (OUR), respirometric index (RI), and respiratory quotient (RQ).
AB  - Composting of several organic wastes of different chemical composition (source
      separated organic fraction of municipal solid waste, dewatered raw sludge,
      dewatered anaerobically digested sludge and paper sludge) was carried out under
      controlled conditions to study the suitability of different biological indexes
      (oxygen uptake rate, respirometric index, and respiratory quotient) to monitor
      the biological activity of the composting process. Among the indexes tested,
      oxygen uptake rate (also referred to as dynamic respirometric index) provided the
      most reliable values of microbial activity in a compost environment. On the other
      hand, values of the static respirometric index measured at process temperature,
      especially in the early stages of the composting process, were significantly
      lower than those of the dynamic index, which was probably due to oxygen diffusion
      limitations present in static systems. Both static and dynamic indexes were
      similar during the maturation phase. Static respirometric index measured at 37
      degrees C should not be used with samples obtained during the thermophilic phase,
      since it resulted in an underestimation of the respiration values. Respiratory
      quotient presented only slight variations when changing the process temperature
      or the waste considered, and its use should be restricted to ensure aerobic
      conditions in the composting matrix.

PMID- 15459908
TI  - Enzymatic resolution for the preparation of enantiomerically enriched D-beta
      heterocyclic alanine derivatives using Escherichia coli aromatic L-amino acid
      transaminase.
AB  - An enzymatic resolution was carried out for the preparation of enriched beta
      heterocyclic D-alanine derivatives using Escherichia coli aromatic L-amino acid
      transaminase. The excess of pyrazole, imidazole, or 1,2,4-triazole reacted with
      methyl-2-acetamidoacrylate in acetonitrile in the presence of potassium carbonate
      at 60 degrees C, directly leading to make the potassium salt of the corresponding
      N-acetyl-beta-heterocyclic alanine derivatives. After the acidic deprotection of
      the N-acetyl group, 10 mM of racemic pyrazolylalanine, triazolylalanine, and
      imidazolylalanine were resolved to D-pyrazolylalanine, D-triazolylalanine, and D
      imidazolylalanine with 46% (85% ee), 42% (72% ee), and 48% (95% ee) conversion
      yield in 18 h, respectively, using E. coli aromatic L-amino acid transaminase (EC
      2.6.1.5). Although the three beta-heterocyclic L-alanine derivatives have similar
      molecular structures, they showed different reaction rates and
      enantioselectivities. The relative reactivities of the transaminase toward the
      beta-heterocyclic L-alanine derivatives could be explained by the relationship
      between the substrate binding energy (E, kcal/mol) to the enzyme active site and
      the distance (delta, A) from the nitrogen of alpha-amino group of the substrates
      to the C4' carbon of PLP-Lys258 Schiff base. As the ratio of the substrate
      binding energy (E) to the distance (delta) becomes indicative value of
      k(cat)/K(M) of the enzyme to the substrate, the relative reactivities of the beta
      heterocyclic L-alanine derivatives were successfully correlated with E/delta, and
      the relationship was confirmed by our experiments.

PMID- 15459909
TI  - Mineralization of LCFA associated with anaerobic sludge: Kinetics, enhancement of
      methanogenic activity, and effect of VFA.
AB  - Long-chain fatty acids (LCFA) associated with anaerobic sludge by mechanisms of
      precipitation, adsorption, or entrapment can be biodegraded to methane. The
      mineralization kinetics of biomass-associated LCFA were established according to
      an inhibition model based on Haldane's enzymatic inhibition kinetics. A value
      around 1,000 mg COD-LCFA..g VSS(-1) was obtained for the optimal specific LCFA
      content that allowed the maximal mineralization rate. For sludge with specific
      LCFA contents of 2,838 +/- 63 and 4,571 +/- 257 mg COD-LCFA..g VSS(-1), the
      specific methanogenic activities in the presence of acetate, butyrate, and
      H(2)/CO(2) were significantly enhanced after the mineralization of the biomass
      associated LCFA. For sludge with a specific LCFA content near the optimal value
      defined by the kinetic model, the effect of adding VFA to the medium was studied
      during the mineralization of the biomass-associated LCFA. Different patterns were
      obtained for each individual substrate. Acetate and butyrate were preferentially
      consumed by the consortium, but in the case of propionate no evidence of a
      sequential consumption pattern could be withdrawn. It was concluded that LCFA do
      not exert a bactericidal neither a permanent toxic effect toward the anaerobic
      consortia. A discussion is addressed to the relative roles of a reversible
      inhibitory effect and a transport limitation effect imposed by the LCFA
      surrounding the cells.

PMID- 15459910
TI  - Activation of lignin peroxidase in organic media by reversed micelles.
AB  - Activation of lignin peroxidase (LIP) in an organic solvent by reversed micelles
      was investigated. Bis(2-ethylhexyl)sulfosuccinate sodium salt (AOT) was used as a
      surfactant to form a reversed micelle. Lyophilized LIP from an optimized aqueous
      solution exhibited no enzymatic activity in any organic solvents examined in this
      study; however, LIP was catalytically active by being entrapped in the AOT
      reversed micellar solution. LIP activity in the reversed micelle was enhanced by
      optimizing either the preparation or the operation conditions, such as water
      content and pH in water pools of the reversed micelle and the reaction
      temperature. Stable activity was obtained in isooctane because of the stability
      of the reversed micelle. The optimal pH was 5 in the reversed micellar system,
      which shifted from pH 3 in the aqueous solution. The degradation reaction of
      several environmental pollutants was attempted using LIP hosted in the AOT
      reversed micelle. Degradation achieved after a 1-h reaction reached 81%, 50%, and
      22% for p-nonylphenol, bisphenol A, and 2,4-dichlorophenol, respectively. This is
      the first report on the utilization of LIP in organic media.

PMID- 15459911
TI  - Continuous cell partitioning using an aqueous two-phase flow system in
      microfluidic devices.
AB  - We present a novel microfluidic system in which an aqueous two-phase laminar flow
      is stably formed, and the continuous partitioning of relatively large cells can
      be performed, eliminating the influence of gravity. In this study, plant cell
      aggregates whose diameters were 37-96 microm were used as model particles. We
      first performed cell partitioning using a simple straight microchannel having two
      inlets and two outlets and examined the effects of the flow rate and the phase
      width on partitioning efficiency. Second, by using a microchannel with a pinched
      segment, the partitioning efficiency was successfully improved. This microscale
      aqueous two-phase flow system can further be incorporated into micro total
      analysis systems (microTAS) or lab-on-a-chip technology, owing to its simplicity,
      applicability, and biocompatibility.

PMID- 15459912
TI  - Comparative proteomic analysis of GS-NS0 murine myeloma cell lines with varying
      recombinant monoclonal antibody production rate.
AB  - We have employed an inverse engineering strategy based on quantitative proteome
      analysis to identify changes in intracellular protein abundance that correlate
      with increased specific recombinant monoclonal antibody production (qMab) by
      engineered murine myeloma (NS0) cells. Four homogeneous NS0 cell lines differing
      in qMab were isolated from a pool of primary transfectants. The proteome of each
      stably transfected cell line was analyzed at mid-exponential growth phase by two
      dimensional gel electrophoresis (2D-PAGE) and individual protein spot volume data
      derived from digitized gel images were compared statistically. To identify
      changes in protein abundance associated with qMab datasets were screened for
      proteins that exhibited either a linear correlation with cell line qMab or a
      conserved change in abundance specific only to the cell line with highest qMab.
      Several proteins with altered abundance were identified by mass spectrometry.
      Proteins exhibiting a significant increase in abundance with increasing qMab
      included molecular chaperones known to interact directly with nascent
      immunoglobulins during their folding and assembly (e.g., BiP, endoplasmin,
      protein disulfide isomerase). 2D-PAGE analysis showed that in all cell lines Mab
      light chain was more abundant than heavy chain, indicating that this is a likely
      prerequisite for efficient Mab production. In summary, these data reveal both the
      adaptive responses and molecular mechanisms enabling mammalian cells in culture
      to achieve high-level recombinant monoclonal antibody production.

PMID- 15459913
TI  - Process development for a recombinant Chinese hamster ovary (CHO) cell line
      utilizing a metal induced and amplified metallothionein expression system.
AB  - The suspension Chinese Hamster Ovary cell line, 13-10-302, utilizing the
      metallothionein (MT) expression system producing recombinant human growth hormone
      (hGH) was studied in a serum-free and cadmium-free medium at different
      fermentation scales and modes of operation. Initial experiments were carried out
      to optimize the concentration of metal addition to induce the MT promoter.
      Subsequently, the cultivation of the 13-10-302 cell line was scaled up from
      spinner flasks into bioreactors, and the cultivation duration was extended with
      fed-batch and perfusion strategies utilizing 180 microM zinc to induce the
      promoter controlling expression of recombinant hGH. It was shown that a fed-batch
      process could increase the maximum cell numbers twofold, from 3.3 to 6.3 x 10(6)
      cell/mL, over those obtained in normal batch fermentations, and this coupled with
      extended fermentation times resulted in a fourfold increase in final hGH titer,
      from 135 +/- 15 to 670 +/- 70 mg/L at a specific productivity q(hGH) value of 12
      pg cell(-1)d(-1). The addition of sodium butyrate increased the specific
      productivity of hGH in cells to a value of approximately 48 pg cell(-1)d(-1),
      resulting in a final hGH titer of over a gram per liter during fed-batch runs. A
      BioSep acoustic cell recycler was used to retain the cells in the bioreactor
      during perfusion operation. It was necessary to maintain the specific feeding
      rates (SFR) above a value of 0.2 vvd/(10(6) cell/mL) to maintain the viability
      and productivity of the 13-10-302 cells; under these conditions the viable cell
      number increased to over 10(7) cell/mL and resulted in a volumetric productivity
      of over 120 mg(hGH) L(-1)d(-1). Process development described in this work
      demonstrates cultivation at various scales and sustained high levels of
      productivity under cadmium free condition in a CHO cell line utilizing an
      inducible metallothionein expression system.

PMID- 15459914
TI  - Safety of video-assisted thyroidectomy versus conventional surgery.
AB  - BACKGROUND: Thyroid gland manipulation, surgical stress response, and
      postoperative outcome in cases of video-assisted thyroidectomy (VAT) and
      conventional thyroidectomy were compared to verify the safety of VAT. METHODS:
      Twenty consenting patients were randomly assigned to undergo VAT or conventional
      thyroidectomy. Serum thyroglobulin levels were monitored as indicators of thyroid
      manipulation, and C-reactive protein and white blood cell count were monitored to
      assess surgical stress response. Thyroid capsule integrity and the presence of
      spilled cells in the thyroid bed were verified. RESULTS: No significant
      differences were found in the indicators of thyroid gland manipulation and
      surgical stress response between groups. No thyroid capsules ruptured, and no
      spilled thyroid cells were found. Patients who had VAT experienced less pain,
      required fewer analgesics, and were more satisfied with the cosmetic result and
      the surgical outcome. CONCLUSIONS: VAT is as safe as conventional thyroidectomy
      and is characterized by a less painful postoperative course and by better
      cosmetic results and postoperative outcome.

PMID- 15459915
TI  - Rapid superselective high-dose cisplatin infusion with concomitant radiotherapy
      for advanced head and neck cancer.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of rapid
      superselective high-dose cisplatin infusion with concomitant radiotherapy for
      previously untreated patients with advanced head and neck cancer. METHODS: Forty
      three patients for whom surgery was contraindicated or who rejected radical
      surgery were given superselective intra-arterial infusions of cisplatin (100-120
      mg/m2/week) with simultaneous intravenous infusion of thiosulfate to neutralize
      cisplatin toxicity and conventional extra-beam radiotherapy (65 Gy/26 f/6.5
      weeks). RESULTS: Thirty-nine patients had stage IV disease, and the remaining
      four had stage III disease. During the median follow-up period of 21 months, the
      3-year locoregional progression-free rates of all patients (n = 43) and patients
      with unresectable disease (n = 24) were 68.9% and 56.4%, respectively. In
      addition, the 3-year overall survival of all patients and patients with
      unresectable disease was 54.0% and 39.6%, respectively. Thirty-five patients
      (81.4%) experienced nonhematologic grade III to IV toxicity, including mucositis
      (n = 16), nausea/vomiting (n = 8), and neurologic signs (n = 2). No patient died
      as a result of treatment toxicity. There are 29 surviving patients without
      evidence of disease, all of whom are able to have oral intake without feeding
      tube support. CONCLUSIONS: We confirmed the efficacy of superselective arterial
      infusion and concomitant radiotherapy, which can concentrate the attack of
      supradose cisplatin on locoregional disease. Even patients with unresectable
      disease can be cured. Further studies are needed to establish the indications,
      long-term outcome, and possible late side effects of this treatment.

PMID- 15459916
TI  - Clinical value of serum squamous cell carcinoma antigen in the management of
      sinonasal inverted papilloma.
AB  - BACKGROUND: Although sinonasal inverted papilloma (IP) is a rare benign tumor, it
      has a tendency to recur and is sometimes associated with squamous cell carcinoma
      (SCC). Therefore, postoperative long-term follow-up of these patients is
      recommended. We previously reported that serum SCC antigen might be a useful
      tumor marker for sinonasal IP. In this study, we investigated whether serum SCC
      antigen level has a correlation with disease status and is useful in the early
      detection of recurrent disease. METHODS: Blood samples for the analysis of serum
      SCC antigen were taken from 28 IP patients before and after surgical treatment.
      RESULTS: Twenty-five (89%) of 28 cases showed evaluated serum SCC antigen levels
      above the upper limit. This marker level decreased in all cases after surgical
      resection. Four of these patients had a recurrence. None of the patients with
      recurrent tumor showed symptoms at the time of detection of their recurrent
      tumor, and recurrence was discovered from elevated levels of SCC antigen.
      CONCLUSIONS: Serum SCC antigen level has a correlation with disease status of IP
      and has a potential to serve as a useful tool for monitoring the course of
      disease. SCC antigen is a reliable tumor marker in the management of sinonasal
      IPs.

PMID- 15459917
TI  - Quality of life in elderly patients with head and neck cancer one year after
      diagnosis.
AB  - BACKGROUND: Little is known about quality of life (QOL) in elderly patients.
      METHODS: Seventy-eight older (> or =70 years) and 105 younger patients (45-60
      years) with carcinoma of the oral cavity, pharynx (stage > or =II), or larynx
      (stage > or =III) completed the European Organization for Research and Treatment
      of Cancer (EORTC) Core Quality of Life Questionnaire and EORTC Head and Neck
      Cancer Quality of Life Questionnaire before treatment. Fifty-one older and 70
      younger patients completed all follow-up questionnaires at 3, 6, and 12 months.
      RESULTS: Before and after treatment, the physical functioning of the older
      patients was worse than that of younger patients. This difference remained
      relatively constant during follow-up and is probably related to normal aging. At
      baseline and 3 months, no other differences were found between both groups. At 6
      months, younger patients reported more pain, but at 12 months no relevant
      differences were found. CONCLUSIONS: Treatment did not affect QOL differently in
      older and younger patients. Therefore, standard treatment should always be
      considered, irrespective of the patient's age.

PMID- 15459918
TI  - Hyperfractionated accelerated radiotherapy in combination with weekly cisplatin
      for locally advanced head and neck cancer.
AB  - BACKGROUND: The purpose of this study was to determine the feasibility and
      efficacy of hyperfractionated accelerated radiotherapy (HFRCB) combined with
      simultaneous chemotherapy with weekly cisplatin (CDDP) in locally advanced
      inoperable head and neck cancer. METHODS: From August 1999 to December 2002, 37
      patients (median age, 59 years) with Union Internationale Contre le Cancer stage
      III (n = 2) and stage IV (n = 35) squamous cell cancer of the oropharynx and
      hypopharynx were treated in a prospective phase I/II trial. Concomitant boost
      radiotherapy (1.8 Gy, days 1-38 and 1.5 Gy boost, days 22-38, twice daily with at
      least a 6-hour interval; total dose 69.9 Gy) and simultaneous cisplatin, 40 mg/m2
      weekly, were given. RESULTS: The median treatment duration was 42 days (range, 38
      46 days). Toxicity was manageable, with neutropenia grade III/IV and
      thrombocytopenia grade IV in seven and one patients, and mucositis grade III/ IV
      in 27 and five patients, respectively. Chemotherapy was restricted to four weekly
      applications in 29 patients mainly because of mucosal toxicity with a median dose
      intensity of 160 mg/m2 (0-200) of cisplatin in 5.5 weeks. With a median follow-up
      of 28 months for living patients, the 2-year overall survival rate was 67%. The
      median overall and relapse-free survival times were 36 and 31 months,
      respectively. CONCLUSION: HFRCB in combination with weekly cisplatin achieves a
      high rate of locoregional control and survival. Four weekly cycles of 40 mg/m2
      cisplatin seem to be the dose limit for most patients.

PMID- 15459919
TI  - Unexpected findings in neck dissection for squamous cell carcinoma: incidence and
      implications.
AB  - BACKGROUND: During the pathologic examination of neck dissections, unexpected
      pathologic findings may occasionally be encountered. These pathologic findings
      may simulate malignant disease and/or have implications on the already
      complicated management of patients with head and neck cancer. METHODS: We
      retrospectively reviewed 202 consecutive patients with a preoperative diagnosis
      of squamous cell carcinoma (SCC), who underwent 307 neck dissections performed by
      a single surgeon and examined by a single pathologist. RESULTS: Ten patients had
      an unexpected finding. These included metastatic papillary thyroid carcinoma,
      leukemia, lymphoma, Warthin's tumor, and tuberculosis. Two of three patients with
      benign-appearing thyroid tissue within lymph nodes received no further treatment,
      and both remained well beyond 6 years. Four patients succumbed to SCC; none died
      from the incidentally discovered pathologic findings. CONCLUSIONS: Unexpected
      pathologic findings may be present in more than 3% of neck dissections. Although
      this is usually indolent, with the underlying SCC remaining the main prognostic
      determinate, it may significantly complicate postoperative management.

PMID- 15459920
TI  - Metastasis to the submandibular gland in head and neck carcinomas.
AB  - BACKGROUND: The purpose of this retrospective chart review was to determine
      whether and how the submandibular gland is involved in metastases of squamous
      cell carcinoma of the head and neck. METHODS: We reviewed the records of all
      patients for whom pathology specimens were available after neck dissection for
      primary head and neck cancers at two institutions. RESULTS: One hundred sixty
      nine patients were included in the study, 27 underwent bilateral neck
      dissections, and 196 submandibular glands were resected and sent for pathology.
      One hundred forty-four glands had normal histologic findings. Normal or benign
      histologic changes were present in 187 glands. Three submandibular glands showed
      invasion from a locally involved lymph node, and six had direct extension from a
      primary lesion. The primary lesions were all ipsilateral to the involved gland
      and originated from cancers of the floor of the mouth, alveolar ridge, and
      tongue. No submandibular glands showed pathologic evidence of metastases.
      CONCLUSIONS: Because the submandibular gland has no intraparenchymal lymph nodes,
      its involvement in upper aerodigestive tract carcinomas must be through extension
      from a locally involved lymph node or the primary tumor. Previous work has
      demonstrated that the submandibular gland can undergo transplantation out of the
      neck with subsequent reimplantation, as a possible means of protection from the
      effects of radiation. We demonstrated the submandibular gland to be involved only
      in cases of ipsilateral oral cavity tumors or metastasis to ipsilateral level I
      lymph nodes. We conclude that it is oncologically sound to consider
      transplantation and replantation of the contralateral submandibular gland for
      patients with head and neck squamous cell carcinoma when level I lymph nodes are
      unlikely to be involved.

PMID- 15459921
TI  - A pilot study of Helicobacter pylori infection and risk of laryngopharyngeal
      cancer.
AB  - BACKGROUND: Squamous cell carcinoma of the laryngopharynx has been linked to
      laryngopharyngeal reflux disease. Helicobacter pylori corpus gastritis decreases
      gastric acid secretion and provides some protection against complications of
      gastroesophageal reflux, including adenocarcinoma of the distal esophagus. The
      aim of this study was to investigate whether H. pylori infection also protects
      against laryngopharyngeal carcinoma. METHODS: This was a case-control study
      comparing patients with histologically confirmed, previously untreated laryngeal
      or pharyngeal squamous cell carcinomas with cancer-free controls selected from a
      pool of hospital-based cancer-free controls identified during a similar time
      period. Each subject completed a self-administered questionnaire that elicited
      information on age, sex, ethnicity, and tobacco and alcohol consumption. The 120
      case subjects were frequency matched to 120 control subjects on age (+/- 5
      years), sex, tobacco use, and alcohol use; all subjects were non-Hispanic whites.
      H. pylori and human papillomavirus type 16 (HPV-16) seropositivity was determined
      by use of an enzyme-linked immunosorbent assay. RESULTS: The serologic assay was
      unsuccessful in one case subject and nine control subjects; therefore, 119 case
      subjects and 111 control subjects were included in the analysis. The proportion
      of subjects with anti-H. pylori immunoglobulin G was similar between the two
      groups (32.8% among cases vs 27.0% among controls; p = .342). Although
      seropositivity was more common in the patients with laryngeal cancer (39.1%) than
      in the patients with pharyngeal cancer (28.8%), this difference was neither
      significant (p = .241) nor associated with a significant risk of laryngeal cancer
      (adjusted odds ratio, 1.53; 95% confidence interval, 0.69-3.41). H. pylori
      seropositivity was more common among patients who were HPV-16 seronegative (38.2%
      vs 22.9%, p = .081), and this was particularly true among patients with laryngeal
      cancer (47.1% vs 18.2%; p = .089). CONCLUSIONS: These results do not show that H.
      pylori infection either protects against or promotes laryngopharyngeal carcinoma.
      However, segregation analyses suggested that H. pylori may play a role in
      laryngeal cancers not associated with HPV-16 infection, and further study in this
      group is warranted.

PMID- 15459922
TI  - Reinnervated anterolateral thigh flap for tongue reconstruction.
AB  - BACKGROUND: Total or near-total glossectomy defects are commonly reconstructed
      with rectus abdominis myocutaneous flaps for coverage. Sensory reinnervation has
      rarely been performed. METHODS: Thirteen consecutive total or near-total
      glossectomy reconstructions were performed in a 12-month period with
      anterolateral thigh flaps with (n = 8) or without (n = 5) sensory reinnervation
      to the lingual nerve. Two-point discrimination, Semmes-Weinstein monofilament
      testing, pain, and temperature testing were performed before and after 12 months
      of surgery. Speech and swallow functions were assessed with an established
      grading system. RESULTS: Innervated flaps had superior sensory recovery to
      noninnervated flaps in all testing modalities. Postoperative radiotherapy may
      delay sensory recovery. Swallow function was better in the innervated group.
      Return of sensation also improves overall patient satisfaction. CONCLUSIONS: The
      reinnervated anterolateral thigh flap is a viable option to reconstruct total or
      near-total glossectomy defects with good speech and swallow functions.

PMID- 15459923
TI  - Surgical treatment of paragangliomas of the carotid bifurcation: results of 36
      patients.
AB  - BACKGROUND: Paragangliomas of the carotid bifurcation are rare and usually benign
      neoplasms arising from the carotid body chemoreceptors. The aim of this
      retrospective study was to report long-term results of carotid bifurcation
      paragangliomas treated in a single institution over a period of 20 years. The
      following variables are described: age, sex, localization, diagnostic workup,
      operative procedure, complications, proportion and characteristics of malignant
      tumors, and cure rates. METHODS: Thirty-six patients,10 men and 26 women, were
      treated. Twenty-three patients had tumors on the right side, 10 patients had
      tumors on the left side, and three patients had bilateral tumors. All patients
      were symptomatic. The most common complaint was a neck mass that had been present
      for 1 to 144 months. All patients had diagnostic procedures done before
      treatment. The most widely used was ultrasonography (26 patients). Angiography
      was performed in 14 patients. RESULTS: All patients underwent complete tumor
      resection. In three cases, resection of the internal carotid was necessary. In
      all patients who underwent internal carotid resection, immediate reconstruction
      was performed. No patients had postoperative strokes. Five patients had
      postoperative nerve palsies. During the follow-up period of 4 months to 12 years,
      no patients had local recurrence develop. Four patients had distant metastasis.
      CONCLUSION: The complete removal of paragangliomas of the carotid bifurcation is
      effective with acceptable morbidity. All recurrences of the malignant tumors were
      distant metastasis.

PMID- 15459924
TI  - Same-day discharge after total thyroidectomy: the value of 6-hour serum
      parathyroid hormone and calcium levels.
AB  - BACKGROUND: The purpose of this study was to determine whether patients who
      undergo total thyroidectomy will have postoperative hypocalcemia develop when
      they reach the critical 6-hour serum levels defined as parathyroid hormone (PTH)
      > or =28 ng/L and simultaneous corrected calcium > or =2.14 mmol/L. METHODS: This
      was a prospective study involving 70 consecutive total thyroidectomy patients.
      There were 51 women and 19 men involved in the study. The mean age was 49.3 years
      (range, 21-76 years). Patients who had completion thyroidectomy or neck
      dissections were excluded. Patients undergoing parathyroidectomy at the time of
      thyroidectomy were also excluded. PTH and corrected calcium levels were measured
      postoperatively at 6, 12, and 20 hours. RESULTS: Hypocalcemia developed in 24%
      (17 of 70) of the patients. Of the 53 patients who remained normocalcemic, 68%
      (36 of 53) reached the 6-hour critical level. None of the hypocalcemic patients
      (0 of 17) attained the 6-hour critical level (chi-square test p < .0001). This
      translates into a specificity of 100% (95% confidence interval [CI], 80.5% to
      100%) and a positive predictive value of 100% (95% CI, 90.1% to 100%).
      CONCLUSIONS: The simultaneous evaluation of PTH and corrected calcium levels 6
      hours after thyroidectomy allows for an accurate prediction of the trend of serum
      calcium. This study enables us to confidently consider same-day discharge for
      most of our thyroidectomy patients.

PMID- 15459925
TI  - Usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography in
      patients with a residual structural abnormality after definitive treatment for
      squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: Residual structural abnormalities after definitive treatment of head
      and neck squamous cell carcinoma (HNSCC) are common and pose difficult management
      problems. The usefulness of fluorine-18 fluorodeoxyglucose positron emission
      tomography (FDG PET) to supplement conventional evaluation with clinical and
      standard radiologic examination (CE) in such patients was assessed. METHODS:
      Fifty-three eligible patients were identified with residual structural
      abnormalities on CE. True disease extent could be validated in 46 patients.
      Patients had a median potential follow-up of 55 months (range, 41-75 months) from
      the date of PET scan to the analysis closeout date. RESULTS: PET had better
      diagnostic accuracy than CE (p = .0002) and induced management change in 21
      patients (40%; 95% confidence interval [CI], 26%-54%), including avoidance of
      unnecessary planned surgery in 14 patients with negative PET. Appropriate
      management change was confirmed in 19 (95%) of 20 evaluable cases. Disease
      presence and extent assessment by PET were significant predictors of survival (p
      < .0001), whereas the extent of disease determined by CE was not. CONCLUSION: PET
      added significantly to the value of CE in restaging disease in patients with
      structural abnormalities after definitive treatment of HNSCC. Management
      decisions based on PET were appropriate in most patients.

PMID- 15459926
TI  - Shoulder function after accessory nerve-sparing neck dissections.
AB  - BACKGROUND: This study was designed to observe the effect of preserving the
      spinal accessory nerve (SAN) during neck dissection (ND) and adjuvant
      radiotherapy (ART) after ND on shoulder function. METHODS: Fifty-seven patients
      with head and neck cancer who had undergone primary tumor resection and various
      types of NDs were enrolled in this prospective study. Postoperative shoulder
      joint range of motion was evaluated by goniometry, and muscle strength was
      measured manually. SAN function was evaluated with electromyography (EMG) with
      respect to percentage of denervation and presence of neurogenic involvement.
      Patients were grouped by treatment as follows: radical ND (RND) versus modified
      radical ND (MRND)/selective ND (SND) and ART versus no ART. RESULTS: Shoulder
      joint range of motion and shoulder muscle strength were significantly better in
      the MRND/SND group than in the RND group. However, EMG findings were similar in
      the RND and MRND/SND groups. When all patients who underwent ND, RND, or MRND/SND
      were compared with the control group, statistically significant changes in
      shoulder joint range of motion and shoulder muscle strength were found. Also,
      denervation and neurogenic involvement of the SAN were significantly higher after
      all NDs than in the control group. ART did not affect range of motion of the
      shoulder joint, shoulder muscle strength, or the degree of denervation and
      neurogenic involvement in any of the ND groups. CONCLUSIONS: ART does not have a
      negative effect on shoulder function after ND. SAN is always functionally
      impaired even if we preserve it macroscopically during ND.

PMID- 15459927
TI  - Postoperative irradiation for squamous cell carcinoma of the oral cavity: 35-year
      experience.
AB  - BACKGROUND: The purpose of this study was to analyze factors influencing outcome
      in patients who received postoperative irradiation for advanced squamous cell
      carcinoma of the oral cavity. METHODS: Between October 1964 and November 2000,
      226 patients with 230 previously untreated primary invasive squamous cell
      carcinomas of the oral cavity were treated postoperatively with continuous-course
      external beam irradiation. All patients had a minimum follow-up of 2 years
      (analysis, November 2002). No patient was lost to follow-up. RESULTS: The 5-year
      actuarial rates of locoregional control by pathologic American Joint Committee on
      Cancer stage were: stage I, 100%; stage II, 84%; stage III, 78%; and stage IV,
      66%. Recurrence of cancer above the clavicles developed in 55 patients (24%). In
      multivariate analysis of locoregional control, positive margins, vascular
      invasion, perineural invasion, extracapsular extension, and T classification
      remained significant. CONCLUSIONS: This article provides additional data defining
      relatively favorable and unfavorable groups of patients in the postoperative
      setting. Dose recommendations are re-examined and selectively increased for high
      risk patients.

PMID- 15459928
TI  - CO2 laser surgery: a larynx preservation alternative for selected hypopharyngeal
      carcinomas.
AB  - BACKGROUND: Transoral CO2 laser surgery (TLS) has demonstrated good oncologic
      results and low morbidity in the treatment of selected laryngeal carcinomas, but
      experience in hypopharyngeal carcinomas (HC) is limited. The aim of this study
      was to evaluate the usefulness of TLS in the treatment of selected HC. METHODS:
      Twenty-eight patients with HC were treated with TLS and neck dissection. Tumors
      with preoperative invasion of thyroid cartilage at CT, deep growth into the
      cervical space or tongue base, and tumors crossing the posterior midline or
      involving the cervical esophagus were excluded. Postoperative radiation to the
      neck was administered when more than one lymph node was involved, when the
      metastasis diameter was greater than 2 cm, or when extranodal spread was found at
      the pathologic study. RESULTS: The sample included two T1, 16 T2, nine T3, and
      one T4 tumors. Stage classification was: II, 21.4%; III, 28.6%; and IV, 50%. Four
      year overall and disease-specific survival rates were 43.4% and 59.4%,
      respectively, with 78.5% function preservation. Nine patients (32.1%) did not
      need a nasogastric feeding tube. The mean duration of the feeding tube in the
      remaining patients was 15.27 +/- 27.3 days. We had two postoperative bleeding
      episodes that required endoscopic coagulation and three postoperative pneumonias
      caused by aspiration. CONCLUSIONS: TLS is an alternative for the treatment of
      selected HC associated with a high larynx preservation rate.

PMID- 15459930
TI  - Resetting endometrial thresholds: we should avoid double standards.

PMID- 15459931
TI  - Assessment of fetal cerebral arterial and venous blood flow before and after
      vaginal delivery or Cesarean section.
AB  - OBJECTIVES: To compare perinatal intracranial arterial and venous blood velocity
      changes between healthy term neonates delivered vaginally or by Cesarean section
      and to correlate these changes with cord blood gases and pH values at birth.
      METHODS: The study involved 43 healthy term neonates who were delivered vaginally
      (n = 20) or by Cesarean section (n = 23). All fetuses/neonates were examined by
      Doppler ultrasound to obtain middle cerebral artery (MCA) and cerebral transverse
      sinus (Tsin) Doppler waveforms on three occasions (before delivery, and 1 h and
      24 h after birth). Pulsatility index (PI) and peak systolic velocity (PSV) for
      MCA and Tsin were measured and compared between neonates who were delivered
      vaginally or by Cesarean section. Umbilical cord blood samples were analyzed for
      umbilical artery and vein pH, pO(2) and pCO(2) and values were correlated with
      MCA and Tsin Doppler indices. RESULTS: MCA-PI increased and MCA-PSV decreased at
      1 h after birth, and Doppler measurements returned to predelivery values at 24 h
      after birth. Tsin Doppler measurements remained unchanged at 1 h and 24 h when
      compared to predelivery values in both the Cesarean and vaginal delivery groups.
      There was a negative correlation between Tsin-PI before birth and umbilical
      venous pH. There was a positive correlation between Tsin-PSV at 1 h after birth
      and umbilical vein pCO(2). CONCLUSIONS: Cerebral arterial blood velocity
      decreases immediately after birth and increases within 24 h, probably as part of
      neonatal adaptation. Cerebral venous blood velocity remains constant during the
      perinatal period and is likely to be regulated in a different and more complex
      manner than that of arterial blood velocity. Mode of delivery does not affect
      cerebral blood velocity.

PMID- 15459932
TI  - Practicing prenatal diagnosis within the law.

PMID- 15459933
TI  - Diagnosing umbilical cord entanglement in monoamniotic twins: becoming easier and
      probably essential...

PMID- 15459934
TI  - Fetal lung lesions: a new classification of fetal lung dysplasia.

PMID- 15459935
TI  - Middle cerebral artery Doppler indices at different sites: prediction of
      umbilical cord gases in prolonged pregnancies.
AB  - OBJECTIVES: To assess the value of middle cerebral artery Doppler indices
      obtained from different sampling sites in predicting umbilical cord gases at
      delivery in prolonged pregnancies. METHODS: This was a prospective study of
      consecutive pregnant women referred for prolonged-pregnancy surveillance. The
      predictive value of distal and proximal middle cerebral artery Doppler indices
      for cord blood gases was evaluated in women who delivered within 48 h of their
      last antenatal test using stepwise multiple regression. RESULTS: There was a
      significant linear correlation between proximal and distal middle cerebral artery
      pulsatility indices (R = 0.777; P < 0.0001), the mean values being 1.49 (SD,
      0.45) and 1.56 (SD, 0.47), respectively. There was also a linear correlation
      between proximal and distal cerebroplacental ratios (R = 0.68; P < 0.0001), the
      mean values being 1.85 (SD, 1.96) and 1.92 (SD, 1.89), respectively. The stepwise
      multiple regression analysis for umbilical artery pH showed that once the distal
      middle cerebral artery pulsatility index was introduced into the model, the
      addition of any variable did not result in a significant improvement of the
      predictive capacity. The model showed a coefficient of determination (R(2)) of
      0.079. There was a significant correlation between umbilical artery pO(2) and
      both proximal middle cerebral artery pulsatility index (positive) and the
      occurrence of elective Cesarean section (negative). This model accounted for 21%
      of the variance (R(2) = 0.21). No other variables added any significant
      prediction for pO(2). CONCLUSIONS: In post-term pregnancies the proximal middle
      cerebral artery pulsatility index significantly predicts umbilical artery pO(2)
      at delivery but does not predict pH. There is a weak association between distal
      middle cerebral artery pulsatility index and pH but, as this only explains 8% of
      the variance, it is of little clinical value.

PMID- 15459936
TI  - Sonographic features of decidualized ovarian endometriosis suspicious for
      malignancy.
AB  - The discovery of an ovarian mass during pregnancy is often a difficult issue
      because of the risk related to surgical intervention during pregnancy. Moreover,
      ultrasound examination is often unable to provide a definitive diagnosis. A case
      of decidualized ovarian endometriosis is presented to highlight the challenges in
      this diagnosis. We report the transvaginal ultrasound findings, including color
      Doppler examination, magnetic resonance characteristics and tumor marker
      longitudinal evaluation during the first trimester of pregnancy, as well as the
      final histological characteristics of the lesion. Decidualization is a rare
      occurrence in ovarian endometriosis and must be differentiated from malignant
      transformation.

PMID- 15459937
TI  - Umbilical cord entanglement in monoamniotic twins.

PMID- 15459938
TI  - Audit on nuchal translucency thickness measurements in Flanders, Belgium: a plea
      for methodological standardization.
AB  - OBJECTIVES: To audit nuchal translucency thickness (NT) measurements for fetal
      aneuploidy screening in Flanders, and to estimate the impact of small variations
      in NT measurement on the screening result of two first-trimester screening
      algorithms: maternal age + NT (Algorithm A), and maternal age + NT + pregnancy
      associated plasma protein-A + free beta-human chorionic gonadotropin (Algorithm
      B). METHODS: We used the database of first-trimester combined screening, as
      collected by the General Medical Laboratory AML in Antwerp, Belgium, between 1
      January 2001 and 1 April 2004. Audit was performed by establishing a delta-NT
      distribution curve for one trainee of The Fetal Medicine Foundation (FMF) and for
      a group of 263 other sonographers, in comparison with the FMF reference values.
      Risks for fetal aneuploidy were calculated at a cut-off value of 1 : 300 for
      Algorithm A and 1 : 150 for Algorithm B. These risks were recalculated in both
      algorithms after a modeled increase of all NT values by 0.1 or 0.2 mm. RESULTS:
      In a total of 592 measurements performed by the FMF trainee, the 5th, 50th and
      95th percentiles of delta-NT measurements were at -0.41, +0.03 and +0.68 mm,
      respectively. These values were close to the FMF reference values. The screen
      positive rate for this set of data was 4.4% (26/592) in both algorithms. For the
      12 555 measurements of the 263 other sonographers, the 5th, 50th and 95th
      percentiles of delta-NT were at -0.81, -0.14 and +0.73 mm, respectively, which
      clearly indicates underestimation of NT in the lower range. In this set of data
      the screen-positive rate was 3.5% for both algorithms (439/12 555 for Algorithm A
      and 436/12 555 for Algorithm B). Also in this group, 5% (59/1186) of negative
      screening results at maternal age > or = 35 years in Algorithm A became positive
      after a modeled 0.1-mm increase in NT, whereas this was only in 1.2% (134/11 369)
      of tests at maternal age < 35 years (P < 0.0001). The overall increase of screen
      positive rate in Algorithm A after an NT modification of +0.1 mm was 1.2% (152/12
      555), significantly more than in Algorithm B (86/12 555; 0.7%) (P < 0.0001).
      CONCLUSION: In Flanders, there is a systematic underestimation of NT in
      comparison with the FMF reference range. Attempts to change these measurements
      according to the FMF criteria are crucial. This will mainly influence the
      screening results of women at advanced maternal age and of NT-based algorithms
      without the use of other parameters.

PMID- 15459939
TI  - Development of the human fetal pons: in utero ultrasonographic study.
AB  - OBJECTIVES: To examine the ultrasonographic feasibility of imaging the fetal pons
      and to construct a reference chart for its normal development during gestation.
      METHODS: A cross-sectional, prospective study on 293 healthy fetuses of low-risk
      pregnancies between 19 and 34 weeks was performed. The transfontanel approach,
      via the abdominal or vaginal routes, was used to evaluate the fetal metencephalon
      (pons and cerebellum). The anteroposterior diameter of the fetal pons was
      measured in a mid-sagittal plane. The longitudinal diameter of the cerebellar
      vermis was measured at the same plane and the vermis-pons ratio (VPR) was
      established. RESULTS: One hundred and forty-four fetuses were in vertex position.
      In 140 (97.2%) satisfactory visualization and measurements of the pons and
      cerebellar vermis were obtained. One hundred and forty-nine fetuses were breech
      presentations and measurements were successfully performed in 147 (98.6%). The
      pons anteroposterior and vermis longitudinal diameters showed a linear
      correlation with gestational age (GA) (r = 0.95 for both measurements; P <
      0.001). The mean VPR was 1.5 (+/-0.1 SD) and did not change in the gestational
      interval that was considered. CONCLUSION: By using the transfontanel approach,
      evaluation of the fetal pons is feasible via the mid-sagittal plane. The
      nomograms developed and the ratio to fetal vermis provides reference data that
      may be helpful when evaluating anomalies of the brainstem.

PMID- 15459940
TI  - Which infertile women should be indicated for sonohysterography?
AB  - OBJECTIVE: To evaluate the indications for transvaginal saline contrast
      sonohysterography (TV-SCSH) in endometrial screening by transvaginal sonography
      in infertile women. METHODS: The study involved 850 consecutive infertile women
      presenting to an outpatient clinic. Using transvaginal ultrasound endometrial
      images were evaluated in the proliferative phase. Abnormal images were classified
      as follows: rugged (R), hyperechoic (H), waved (W), or thick (T). Clinical
      symptoms such as hypermenorrhea, dysmenorrhea and abnormal uterine bleeding were
      also recorded. Abnormal endometrial images were further evaluated on TV-SCSH. Age
      matched women with normal endometrial images underwent TV-SCSH as controls.
      RESULTS: The endometrial pattern was abnormal in 111 patients (13.1%). Lesions
      that had been identified by TV-SCSH including endometrial polyps (44 cases),
      submucosal myomata (29 cases), and intramural myomata with mucosal extension (24
      cases) were largely associated with the R and/or the H pattern, the W or the T
      pattern, and the W pattern, respectively. Sensitivity and specificity of the
      abnormal endometrial image for any lesion were 100% and 91.5%, respectively.
      Sixty-four patients (59.3%) were asymptomatic despite an abnormal endometrial
      image. CONCLUSIONS: TV-SCSH should be performed on selected patients following
      assessment of endometrial images on transvaginal sonography in order to diagnose
      intra- and pericavitary lesions in infertile women.

PMID- 15459941
TI  - The fetal esophagus: anatomical and physiological ultrasonographic
      characterization using a high-resolution linear transducer.
AB  - OBJECTIVE: To study the sonographic anatomy and physiology of the human fetal
      esophagus during the mid-trimester of pregnancy using a high-resolution linear
      transducer. METHODS: This was a prospective observational study of the fetal
      esophagus between 19 and 25 weeks' gestation. The study was performed in 60
      consecutive fetuses, after a normal anatomy scan, using a 5-13-MHz matrix array
      wide-band transducer. During the examination the collapsed esophagus was first
      visualized, and followed by a 5-min video recording in order to demonstrate
      luminal patency and peristaltic waves. RESULTS: Complete anatomical visualization
      of the esophagus was possible in 52 (86.7%) patients and at least partial
      visualization in 58 (96.7%) patients. Three different patterns of esophageal
      motility were observed: a simultaneous and short opening of the whole esophagus
      was found in 35 (58.3%) fetuses; a segmental, peristalsis-like movement from the
      pharynx, through the mediastinum, and into the stomach was found in 18 (30%)
      fetuses; and in one fetus reflux-like passage of solid contents from the stomach
      was observed. The mean time required for demonstration of esophageal patency was
      96.1 (range, 10-300) s. CONCLUSIONS: Demonstration of normal anatomy and
      physiological activity of the fetal esophagus is feasible using appropriate
      transducers. The most commonly observed pattern of esophageal motility in the mid
      trimester of pregnancy is the simultaneous relaxation of the upper and lower
      esophageal sphincters with concurrent opening of the esophageal lumen from the
      upper thorax to the stomach. Demonstration of a patent esophagus may be helpful
      in fetuses with suspected esophageal atresia.

PMID- 15459942
TI  - Modeling of receptor mimics that inhibit superantigen pathogenesis.
AB  - Staphylococcal enterotoxins SEB and SEC3 and toxic shock syndrome toxin TSST-1
      act as superantigens by overstimulating the human immune system and thereby
      compromise host defense. The mechanism of pathogenesis is explained on the basis
      of superantigen binding to the MHC class II receptor on the antigen presenting
      cell and to the T cell receptor (TcR) on the T cell. SEB, SEC3 and TSST-1 bind as
      intact proteins and make contacts with the alpha1 subdomain (DRalpha) of MHC
      class II and Vbeta subdomain of TcR. SEB, SEC3 and TSST-1 show specificities for
      different TcRVbeta isoforms. We have designed three different chimeras linking
      the same DRalpha with different TcRVbeta isoforms to specifically target SEB,
      SEC3 and TSST-1 and inhibit their pathogenesis. Here, we show by molecular
      modeling that the DRalpha, TcRVbeta and linker of a given chimera interact with
      the target superantigen in a type-specific manner. An initial model of the
      complex is constructed on the basis of observed inter-molecular contacts between
      DRalpha/TcRVbeta and the superantigens. A constant temperature (300 K) 200 ps
      molecular dynamics is performed to sample different conformations of a chimera
      superantigen complex by utilizing the flexibility of the (GSTAPPA)(2) linker
      while maintaining the native folds of superantigen, DRalpha and TcRVbeta and the
      observed intermolecular contacts. After equilibration, 100 molecular dynamic
      snapshots are minimized and analyzed. This provides descriptions of various
      pairwise interactions at the contact interface in the complex and important clues
      on single site mutations on the chimera that may enhance the stability of a given
      superantigen-chimera complex.

PMID- 15459943
TI  - Gamma-vinyl GABA (vigabatrin) blocks the expression of toluene-induced
      conditioned place preference (CPP).

PMID- 15459944
TI  - Association study between brain-derived neurotrophic factor gene polymorphisms
      and methamphetamine abusers in Japan.
AB  - Several lines of evidence suggest that genetic factors might contribute to drug
      abuse vulnerability. Recent genomic scans for association demonstrated that the
      brain-derived neurotrophic factor (BDNF) gene was associated with drug abuse
      vulnerability. In this study, we analyzed association of two BDNF gene single
      nucleotide polymorphisms (SNPs), 132C > T (C270T named formerly) in the noncoding
      region of exon V and 196G > A (val66met) in the coding region of exon XIIIA, with
      methamphetamine (MAP) abuse in Japan. No significant differences were found in
      the frequency of the genotype or allele in these two SNPs between MAP abusers and
      controls (132C > T in exon V: genotype, P = 0.586, allele, P = 0.594; 196G > A
      (val66met) in exon XIIIA: genotype, P = 0.889, allele, P = 0.713). Furthermore,
      there was no difference between clinical parameters (e.g., prognosis psychosis,
      spontaneous relapse, or poly-substance abuse) and the two SNPs of BDNF gene.
      These results suggest that the two SNPs (132C > T in exon V and 196G > A
      (val66met) in exon XIIIA) of the BDNF gene may not be associated with Japanese
      MAP abusers. This article contains supplementary material, which may be viewed at
      the American Journal of Medical Genetics website at
      http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.

PMID- 15459945
TI  - Role of blooming in determining the storage stability of lipid-based dosage
      forms.
AB  - Gelucire 50/13 alone and solid dispersions in this material containing two model
      drugs (10% w/w caffeine and paracetamol) have been studied with a view to
      establishing the mechanism underpinning changes in drug-release characteristics
      as a function of storage time and temperature. The lipid systems were fabricated
      into tablets and stored for up to 180 days at temperatures of 20 and 37 degrees
      C. The dispersions were studied using differential scanning calorimetry (DSC),
      scanning electron microscopy, and dissolution testing. DSC studies indicated that
      the Gelucire 50/13 exists in two principal melting forms (melting points 38 and
      43 degrees C) that undergo transformation to the higher melting form on storage
      at 37 degrees C. Scanning electron microscopy studies indicated that the systems
      exhibit "blooming," with crystal formation on the surface being apparent on
      storage at both temperatures. The dissolution rate increased on storage, with the
      effect being particularly marked at higher storage temperatures and for the
      paracetamol systems. However, whereas these changes corresponded well to those
      seen for the morphology, the correlation between the changes in dissolution and
      those of the DSC profiles was poor. The study has suggested a novel explanation
      for the storage instability of Gelucire 50/13 whereby the change in dissolution
      is associated not with molecular rearrangement as such but with the gross
      distribution of the constituent components, this in turn altering the physical
      integrity of the lipid bases.

PMID- 15459946
TI  - Contribution of the paracellular route to the pH-dependent epithelial
      permeability to cationic drugs.
AB  - The aim of this work was to investigate the contribution of the paracellular
      route to the pH-dependent permeability to cationic drugs in three models
      expressing different drug permeabilities: hexadecane membranes (HDMs), Caco-2,
      and 2/4/A1 cell monolayers. The high- and low-permeability drugs alfentanil and
      cimetidine were used as model drugs. The paracellular permeability was
      calculated: 1. from the assumption that the ionized form (P(mi)) permeates a cell
      monolayer only by the paracellular route, and 2. on basis of the pore-restricted
      diffusion. For both drugs, sigmoidal relationships between membrane permeability
      and pH were observed in all models. The P(mi) was in excellent agreement with the
      paracellular permeability of cimetidine in the two cell models, whereas no
      significant P(mi) of the drugs could be observed in HDM. The results showed that
      the paracellular route has a significant role in the permeability of small basic
      hydrophilic drugs, such as cimetidine in leaky, small intestinal-like epithelia
      such as 2/4/A1. By contrast, in tighter epithelia such as Caco-2 and in
      artificial membranes such as HDM, the permeability of the ionized forms of the
      drugs and the paracellular permeability are lower or insignificant, respectively.
      These findings will have implications in the experimental design and data
      interpretation of pH-dependent drug transport experiments in cell culture models
      as well as in artificial membrane models such as HDM and parallel artificial
      membrane permeability assay (PAMPA).

PMID- 15459947
TI  - Kinetics and mechanism of degradation of epothilone-D: an experimental anticancer
      agent.
AB  - The objective of this study was to investigate the stability and the degradation
      pathway of epothilone-D (Epo-D), an experimental anticancer agent. In pH range 4
      9, Epo-D displayed pH-independent stability and the highest stability was
      observed at pH 1.5-2 where its thiazole group is protonated. Increasing the pH >9
      or <1.5 resulted in an increase in the degradation rate. Epo-D contains an ester
      group that can be hydrolyzed. The formation of the hydrolytic product was
      confirmed by the nuclear magnetic resonance (NMR), fast atom bombardment mass
      spectroscopy and liquid chromatography/mass spectroscopy/mass spectroscopy
      techniques. The largely sigmoidal pH-rate profile is not consistent with the
      normal pH dependency of ester hydrolysis involving an addition/elimination
      mechanism. Hence, a hydrolysis mechanism through a carbonium ion was suggested.
      At pH 4 and 7.4, no buffer catalysis was observed (0.01, 0.02, and 0.05 M
      buffers) and no significant deuterium kinetic solvent isotope effect was noted.
      The degradation was very sensitive to changes in the dielectric constant of the
      solvents as significant enhancement in the stability was observed in buffer
      acetonitrile and 0.1 M (SBE)7m-beta-cyclodextrin solutions compared with just
      buffer, suggesting that the rate-determining step in the degradation pathway
      involved formation of a polar transition state. Mass spectral analysis of the
      reaction run in 18O water was consistent with incorporation of the 18O in the
      alcohol hydroxyl rather than the carboxylate group. These observations strongly
      support the carbonium ion mechanism for the hydrolysis of Epo-D in the pH range 4
      9. A pKa value of 2.86 for Epo-D was estimated from the fit of the pH-rate
      profile. This number was confirmed independently by the changes in ultraviolet
      absorbance of Epo-D as a function of pH (pKa 3.1) determined at 25 degrees C and
      the same ionic strength.

PMID- 15459948
TI  - Development of an in vitro model for premature neonatal skin: biophysical
      characterization using transepidermal water loss.
AB  - The objective was to develop an in vitro model for the developing skin of the
      premature neonate. Barriers of different levels of efficiency were produced by
      differentially tape-stripping the stratum corneum (SC) from the skin of excised
      porcine ears, and were characterized by measurements of transepidermal water loss
      (TEWL). In this way, it was possible to express the recorded TEWL as a function
      of percentage SC thickness (F) generating the following relationship: TEWL = 2.7
      + 41.exp [- 0.028.F]. These data were then compared to previously published in
      vivo measurements of TEWL obtained from a population of premature neonates at
      various post-conceptional ages (PCA). The latter conformed to a remarkably
      parallel relationship to that found in vitro with the porcine skin model, namely
      TEWL = 3.3 + 41.exp [-0.026.(PCA-160)]. It can be suggested, therefore, that the
      empirically adjusted PCA (i.e., PCA-160) correlates closely with the developing
      thickness of the neonate's SC. The corollary is that porcine skin, in vitro, tape
      stripped to a particular level, can provide a barrier corresponding to a specific
      degree of neonate maturation and can serve, hence, as a useful tool with which to
      explore whether transdermal drug delivery in this unique patient population may
      be beneficial.

PMID- 15459949
TI  - Gravity-induced coating flows of vaginal gel formulations: in vitro experimental
      analysis.
AB  - Efficacy of topical microbicidal drug delivery formulations against HIV depends
      in part on their coating distributions and retention on vaginal epithelium. This
      study focused on gravity-induced coating flows of vaginal gels, and effects of
      formulation composition and surface wettability on coating. We hypothesized that
      presence of a yield stress, and surface wettability, affect coating. Experiments
      imaged and analyzed coating flows of gels on inclined model hydrophilic or
      hydrophobic surfaces. The in vitro wettability conditions bracket those believed
      to exist on vaginal epithelium in vivo. Six commercial vaginal gels were studied:
      three polyacrylic acid-based (PAA) and three cellulose-based. Our research group
      uses these gels in complementary human in vivo studies and other in vitro
      experimental analyses; this study is a first step in linking the in vivo and in
      vitro measurements. Coating by PAA gels was different from cellulose-based gels:
      the former exhibited yield stresses, which prevented initial gel shape from
      deforming during sliding. Coating flows of cellulose gels depended upon surface
      wettability. The slipping rates of the PAA gels ranked inversely with fitted
      yield stress values. The coating flow rates of the cellulose gels (hydrophilic
      surface) did not correlate with consistency index, but ranked inversely with the
      shear-thinning index. This study introduces a simple methodology for comparing
      trial formulations and relating their flows to gel constituents and physical
      properties. It also suggests differences in coating by current commercial gels.

PMID- 15459950
TI  - Adhesive tablet effective for treating canker sores in humans.
AB  - A new mucoadhesive tablet, which releases natural active agents for pain
      reduction and rapid healing of canker sores, has been prepared and characterized.
      Adhesive tablets were prepared by compression molding of mixed powders of
      crosslinked polyacrylic acid and hydroxypropyl cellulose, absorbed with citrus
      oil and magnesium salt. The rate of tablet erosion and the rates of citrus oil
      and magnesium release were determined as well as the adhesiveness of the tablet
      using bovine gingival tissue and an Instron tensiometer. A clinical trial was
      conducted on 248 volunteers who had canker sores. Tablets adhere well to the
      mucosal tissue and gradually erode for 8 h releasing the citrus oil in a zero
      order pattern whereas the magnesium is released during a period of 2 h. Both
      experimental and plain tablets were effective in reducing pain and decreasing
      healing time (p < 0.05) without adverse side effects. However, the tablets loaded
      with active agents were more effective.

PMID- 15459952
TI  - A paradigm for single nucleotide polymorphism analysis: the case of the
      acetylcholinesterase gene.
AB  - Acetylcholinesterase (AChE) plays a crucial physiological role in termination of
      impulse transmission at cholinergic synapses through rapid hydrolysis of
      acetylcholine. It is a highly conserved molecule, and only a few naturally
      occurring genetic polymorphisms have been reported in the human gene. The goal of
      the present study was to make a systematic effort to identify natural single
      nucleotide polymorphisms (SNPs) in the human ACHE gene. To this end, the genomic
      coding sequences for acetylcholinesterase of 96 unrelated control individuals
      from three distinct ethnic groups were analyzed. A total of 13 ACHE SNPs were
      identified, 10 of which are newly described, and five that should produce amino
      acid substitutions [c.101G>A (p.Arg34Gln), c.169G>A (p.Gly57Arg), c.1031A>G
      (p.Glu344Gly), c.1057C>A (p.His353Asn), and c.1775C>G (p.Pro592Arg)]. Population
      frequencies of 11 of the 13 SNPs were established in four different populations:
      African Americans, Ashkenazi Jews, Sephardic Jews, and Israeli Arabs; 15
      haplotypes and five ethnospecific alleles were identified. The low number of SNPs
      identified until now in the ACHE gene is ascribed to technical hurdles arising
      from the high GC content and the presence of numerous repeat sequences, and does
      not reflect its intrinsic heterozygosity. Among the SNPs resulting in an amino
      acid substitution, three are within the mature protein, mapping on its external
      surface: they are thus unlikely to affect its catalytic properties, yet could
      have antigenic consequences or affect putative protein-protein interactions.
      Furthermore, the newly identified SNPs open the door to a study of the possible
      association of AChE with deleterious phenotypes-such as adverse drug responses to
      AChE inhibitors employed in treatment of Alzheimer patients and hypersensitivity
      to pesticides.

PMID- 15459953
TI  - Polymorphism analysis within the HLA-A locus by universal oligonucleotide array.
AB  - Human leukocyte antigen (HLA) class I genes present some of the most complex
      single nucleotide polymorphism (SNP) patterns in the human genome. HLA typing is
      therefore extremely challenging. In this article, we use the ligation detection
      reaction (LDR) combined with a universal array (UA) as a robust and efficient
      method to analyze SNPs within the HLA-A region that includes HLA-A alleles of
      interest for immunotherapy in tumor diseases. The LDR, combined with a UA
      platform, has been optimized for the detection of 27 alleles distributed within
      exons 2 and 3 of HLA-A. The assay involves the amplification by PCR of the HLA-A
      genomic region (1,900 bp), the cycled ligation reaction, followed by the capture
      of ligated products through hybridization onto a UA. Each slide was designed to
      allow the detection of up to eight samples in parallel. The PCR/LDR/UA HLA-A
      assay was evaluated by analyzing 62 individuals (31 homozygous and 31
      heterozygous) previously typed by direct sequencing. We demonstrate that the
      microarray genotyping procedure described here is a robust and efficient method
      for unambiguous detection of HLA alleles. HLA genotyping by PCR/LDR/UA is in
      perfect agreement with typing obtained by direct sequencing. Our results clearly
      demonstrate that the combination of enzymatic processing (LDR) and a
      demultiplexing hybridization onto a UA is a robust tool for SNP discrimination
      within the highly polymorphic HLA region. We demonstrate the specificity and
      efficiency of such an approach, suggesting the feasibility of a PCR/LDR/UA low
      resolution HLA typing procedure.

PMID- 15459954
TI  - Mechanisms underlying responsiveness to tetrahydrobiopterin in mild
      phenylketonuria mutations.
AB  - A subtype of phenylalanine hydroxylase (PAH) deficiency that responds to cofactor
      (tetrahydrobiopterin, BH4) supplementation has been associated with
      phenylketonuria (PKU) mutations. The underlying molecular mechanism of this
      responsiveness is as yet unknown and requires a detailed in vitro expression
      analysis of the associated mutations. With this aim, we optimized the analysis of
      the kinetic and cofactor binding properties in recombinant human PAH and in seven
      mild PKU mutations, i.e., c.194T>C (p.I65T), c.204A>T (p.R68S), c.731C>T
      (p.P244L), c.782G>A (p.R261Q), c.926C>T (p.A309V), c.1162G>A (p.V388M), and
      c.1162G>A (p.Y414C) expressed in E. coli. For p.I65T, p.R68S, and p.R261Q, we
      could in addition study the equilibrium binding of BH4 to the tetrameric forms by
      isothermal titration calorimetry (ITC). All the mutations resulted in catalytic
      defects, and p.I65T, p.R68S, p.P244L, and most probably p.A309V, showed reduced
      binding affinity for BH4. The possible stabilizing effect of the cofactor was
      explored using a cell-free in vitro synthesis assay combined with pulse-chase
      methodology. BH4 prevents the degradation of the proteins of folding variants
      p.A309V, p.V388M, and p.Y414C, acting as a chemical chaperone. In addition, for
      wild-type PAH and all mild PKU mutants analyzed in this study, BH4 increases the
      PAH activity of the synthesized protein and protects from the rapid inactivation
      observed in vitro. Catalase and superoxide dismutase partially mimic this
      protection. All together, our results indicate that the response to BH4
      substitution therapy by PKU mutations may have a multifactorial basis. Both
      effects of BH4 on PAH, i.e., the chemical chaperone effect preventing protein
      misfolding and the protection from inactivation, may be relevant mechanisms of
      the responsive phenotype.

PMID- 15459955
TI  - Germline mutations of the POU6F2 gene in Wilms tumors with loss of heterozygosity
      on chromosome 7p14.
AB  - Wilms tumor (WT) is a kidney malignancy of childhood characterized by highly
      heterogeneous genetic alterations. We previously reported the molecular and
      cytogenetic characterization of a WT (Case 30) carrying an interstitial deletion
      in chromosome 7p14 between markers D7S555 and D7S668. Loss of heterozygosity
      (LOH) analyses had revealed that this same region was lost in 8 out of 38
      examined WTs, suggesting that the identified interval contains a putative tumor
      suppressor gene. To confirm this hypothesis, in this work, we analyzed an
      additional 35 WTs, four of which showed LOH in the region of interest.
      Furthermore, we were able to more accurately define the extension of the deletion
      in Case 30, mapping it within an interval not exceeding 390 kb, proximally to
      D7S555. To date, only a single expressed gene, POU6F2 (the POU domain, class 6,
      transcription factor 2; also known as RPF1), has been recognized in this
      interval. Sequencing of the gene in the 12 WTs showing LOH and in a corresponding
      numbers of WT cases without LOH, led to the identification of two germline
      nucleotide substitutions. The first occurred in the 5'-untranslated region, while
      the second caused an amino acid change in a glutamine repeat domain. These
      mutations, whose occurrence was not observed in more than 100 control subjects,
      were detected in two patients showing the loss of the constitutionally wild-type
      allele in tumor DNA. Together with the finding of the expression of the POU6F2
      mouse homolog in both fetal and adult kidney, our observations suggest that the
      gene is a tumor suppressor and is involved in hereditary predisposition to WT.

PMID- 15459956
TI  - CRB1 mutation spectrum in inherited retinal dystrophies.
AB  - Mutations in the Crumbs homologue 1 (CRB1) gene have been reported in patients
      with a variety of autosomal recessive retinal dystrophies, including retinitis
      pigmentosa (RP) with preserved paraarteriolar retinal pigment epithelium (PPRPE),
      RP with Coats-like exudative vasculopathy, early onset RP without PPRPE, and
      Leber congenital amaurosis (LCA). We extended our investigations of CRB1 in these
      retinal dystrophies, and identified nine novel CRB1 sequence variants. In
      addition, we screened patients with "classic" RP and classic Coats disease
      (without RP), but no pathologic sequence variants were found in the CRB1 gene. In
      total, 71 different sequence variants have been identified on 184 CRB1 alleles of
      patients with retinal dystrophies, including amino acid substitutions,
      frameshift, nonsense, and splice site mutations, in-frame deletions, and large
      insertions. Recent studies in two animal models, mouse and Drosophila, and in
      vivo high-resolution microscopy in patients with LCA, have shed light on the role
      of CRB1 in the pathogenesis of retinal dystrophies and its function in the
      photoreceptors. In this article, we provide an overview of the currently known
      CRB1 sequence variants, predict their effect, and propose a genotype-phenotype
      correlation model for CRB1 mutations.

PMID- 15459957
TI  - Molecular analysis of SMA patients without homozygous SMN1 deletions using a new
      strategy for identification of SMN1 subtle mutations.
AB  - Spinal muscular atrophy (SMA) is a common autosomal recessive disease. SMA is
      linked to the 5q13 locus in 95% of patients, and in at least 98% of them, the
      SMN1 homozygous deletion is found. Compound heterozygous patients, who have an
      SMN1 deletion associated with a subtle mutation, appear undeleted with the common
      molecular diagnostic test that detects only the homozygous absence of SMN1. In
      these patients, mutation screening in SMN1 is hampered by the presence of several
      copies of the highly homologous SMN2 gene. Here, we present a rapid and reliable
      strategy for detecting SMN mutations using long-range PCR, which avoids cloning
      and cDNA analysis. Using this method, we found 10 mutations, including five
      mutations never reported previously and five recurrent mutations; some of them
      are probably population-specific. Marker analysis of the 5q13 locus in these
      mutations showed common haplotypes, supporting the hypothesis of a common
      ancestor rather than a hot spot sequence. We also evaluate the suitability of
      automated SSCA and DHPLC for mutation scanning.

PMID- 15459958
TI  - Mutation analysis of NR0B2 among 1545 Danish men identifies a novel c.278G>A
      (p.G93D) variant with reduced functional activity.
AB  - Variations of the small heterodimer partner (SHP, NR0B2) gene, an atypical
      nuclear receptor that inhibits transactivation by hepatocyte nuclear factor (HNF)
      4alpha, are associated with obesity among Japanese. The purpose of the study was
      to evaluate the prevalence of SHP variants among obese Danish men. Using combined
      SSCP and heteroduplex analysis, we analyzed the entire coding region of SHP for
      variants in a cohort of 750 Danish men with early-onset obesity and genotyped a
      cohort of 795 nonobese control subjects using PCR-RFLP. Functional analyses of
      the identified coding region variants were performed in both MIN6-m9 and HepG2
      cell lines. A total of five novel variants, including three missense variants
      (c.100C>G [p.R34G], c.278G>A [p.G93D], and c.415C>A [p.P139H]) and two silent
      variants (c.65C>T [p.Y22Y] and c.339G>A [p.P113P]) were identified. Moreover, the
      previously reported c.512G>C [p.G171A] polymorphism was identified. The 171A
      allele was not associated with obesity (p = 0.07). The 34G, 93D, and 139H-alleles
      were rare variants, which were found only among obese subjects. Among the four
      coding region variants, the 93D-allele showed a reduced in vitro inhibition of
      the HNF-4alpha transactivation of the HNF-1alpha promoter expression when
      expressed in MIN6-m9 and HepG2 cell lines (p<0.01). In contrast to reported
      findings among obese Japanese, functional variants are rare among Danish men. A
      functional 93D variant of SHP was identified in 1 out of 750 obese and in none of
      795 nonobese control subjects. Further large-scale population studies are
      necessary to assess the clinical impact of this rare variant on obesity risk
      among European subjects.

PMID- 15459959
TI  - Familial adenomatous polyposis: aberrant splicing due to missense or silent
      mutations in the APC gene.
AB  - Familial adenomatous polyposis (FAP) is caused by germline mutations in the tumor
      suppressor gene APC. To date, the relevance of rare exonic single-base
      substitutions at nucleotide positions close to splice sites that are predicted to
      result in missense or silent (SNP) variants or substitutions in introns at splice
      site positions that are not highly conserved has not been systematically examined
      in FAP patients. In 34 index patients, we identified 26 different heterozygous
      single-base substitutions at or close to the splice sites. We characterized five
      exonic mutations in exon 4 (c.423G>T), exon 14 (c.1956C>T, c.1957A>G, and
      c.1957A>C), and exon 15 (c.1959G>A) by transcript analysis and by splice
      prediction programs (BDGP, SpliceSiteFinder, and ESEfinder). The splicing
      patterns of these variants were compared to those of 16 different substitutions
      at highly or less-conserved intronic splice-site positions, and to normal
      controls. In addition, we analyzed cosegregation of the variants with affected
      family members and examined the genotype-phenotype correlation. We could
      demonstrate that the four unclear variants in exon 4 and 14 that are predicted to
      result in missense or silent mutations in fact lead to complete exon skipping due
      to aberrant splicing; one possible explanation for this observed effect might be
      the disruption of exonic splicing enhancer (ESE) motifs. In contrast, the
      substitution at the first position of exon 15 seems to actually be a silent
      variant. We present the first systematic evaluation of different single-base
      substitutions in APC at or close to splice sites at transcript level. We show
      that the consequence of exonic mutations cannot be evaluated only by the
      predicted change in amino acid sequence but rather by the change at DNA level.
      The functional analysis of variants with unknown pathogenic effect plays an
      important role in increasing the mutation detection rate and achieving validation
      of predictive testing.

PMID- 15459960
TI  - Prenatally diagnosed cystic neuroblastoma.

PMID- 15459961
TI  - Gilbert syndrome as differential diagnosis of hyperbilirubinemia in acquired
      aplastic anemia.

PMID- 15459962
TI  - A diagnosis dilemma of back pain in non-Hodgkin lymphoma.

PMID- 15459963
TI  - Widespread gene transduction to the central nervous system by adenovirus in
      utero: implication for prenatal gene therapy to brain involvement of lysosomal
      storage disease.
AB  - BACKGROUND: In some lysosomal storage diseases, considerable alterations of the
      central nervous system (CNS) occur prior to birth and neurodegeneration
      progresses rapidly soon after birth causing early death in patients. No effective
      treatment is available after birth. Treatment may need to be initiated before
      birth to prevent the onset or progression of neurological changes and thereby
      irreversible brain damage. The aim of this study is to investigate the
      feasibility and effectiveness of brain-directed prenatal gene therapy for
      lysosomal storage diseases. METHODS: Recombinant adenovirus encoding the lacZ
      gene was injected into the lateral ventricles of mouse embryos and the pattern of
      gene transduction to the CNS was investigated. In the therapeutic experiment,
      adenovirus expressing beta-glucuronidase was injected into the cerebral
      ventricles of the embryos of mucopolysaccharidosis VII mice and the therapeutic
      effects on the brain were evaluated. RESULTS: Injection of adenoviral vectors to
      the cerebral ventricles of mouse embryos led to widespread gene transduction
      throughout the brain and the spinal cord and transgene expression persisted over
      10 months in those surviving the procedure. The prenatal transduction of the
      therapeutic gene to the brain of the mucopolysaccharidosis VII mouse efficiently
      prevented lysosomal storage in most brain cells before birth until 4 months after
      birth. CONCLUSIONS: Brain-directed in utero gene therapy through an intra
      ventricular route would be an effective strategy to treat some lysosomal storage
      diseases with early and severe CNS alterations.

PMID- 15459964
TI  - Production of lentiviral vectors by transient expression of minimal packaging
      genes from recombinant adenoviruses.
AB  - BACKGROUND: The potential of lentiviral vectors for clinical gene therapy has not
      yet been evaluated. One of the reasons is the cytotoxicity of lentiviral
      packaging genes which makes the generation of stable producer cell lines
      difficult. Therefore, a novel packaging system for lentiviral vectors based on
      transient expression of packaging genes by recombinant adenoviruses was
      developed. METHODS: Adenoviral vectors expressing VSV-G, codon-optimized HIV-1
      gag-pol, and codon-optimized SIV gag-pol under the control of a tetracycline
      regulatable promoter (adenoviral lenti-pack vectors) were constructed and the
      production levels of this vector system were evaluated. RESULTS: The generated
      adenoviral lenti-pack vectors could be grown to high titers when transgene
      expression was suppressed and no evidence for instabilities was obtained. Cells
      stably transfected with a SIV-based vector construct were converted into
      lentiviral vector producer cells by infection with the adenoviral lenti-pack
      vectors. Lentiviral vector titers obtained were as high as vector titers obtained
      by transient cotransfection experiments. A protocol was developed that allowed
      preparation of lentiviral vector stocks with undetectable levels of contaminating
      adenoviral lenti-pack vectors. CONCLUSIONS: The adenoviral lenti-pack vectors
      described should provide a convenient alternative approach to inducible packaging
      cell lines for large-scale lentiviral vector production. Transient expression of
      cytotoxic lentiviral packaging genes by the adenoviral lenti-pack vectors
      circumvents loss of titers during prolonged culture of packaging cell lines. The
      design of the adenoviral lenti-pack vectors should reduce the risk of transfer of
      packaging genes to target cells and at the same time provide flexibility with
      respect to the lentiviral vector constructs that can be packaged.

PMID- 15459965
TI  - Skin permeation, biodistribution, and expression of topically applied plasmid
      DNA.
AB  - BACKGROUND: Topical application is emerging as a new route of gene delivery.
      However, the extent of skin permeation and the in vivo fate of topically applied
      plasmid DNA are not fully understood. METHODS: In vitro permeation of plasmid DNA
      across human skin and keratinocyte layers was tested using Franz diffusion cells.
      In vivo absorption and biodistribution of topically applied plasmid in mice were
      determined using quantitative polymerase chain reaction (PCR). The expression
      levels of plasmid DNA in various tissues were measured by semiquantitative
      reverse transcription PCR. RESULTS: In vitro, topically applied DNA was capable
      of penetrating human skin and keratinocyte layers. Following topical application
      of plasmid DNA onto murine skin, the levels of plasmid DNA in the serum peaked at
      4 hr. At 24 hr post-dose, topically applied DNA existed at higher levels than
      intravenously administered DNA in almost all tissues, and induced 11.4- and 22
      fold higher mRNA expression in muscle and skin, respectively. Moreover, the
      topical route showed sustained expression of plasmid DNA in the regional lymph
      nodes over 5 days, whereas the intravenous route did not. CONCLUSIONS: Taken
      together, our results show that topically applied plasmid DNA is capable of
      permeating the skin and being expressed for prolonged periods in various tissues
      including lymph nodes. This suggests that skin may provide an appealing,
      noninvasive route of delivery for DNA vaccines and other therapeutic genes.

PMID- 15459966
TI  - Somatic gene targeting with RNA/DNA chimeric oligonucleotides: an analysis with a
      sensitive reporter mouse system.
AB  - BACKGROUND: Targeted gene correction provides a potentially powerful method for
      gene therapy. RNA/DNA chimeric oligonucleotides were reported to be able to
      correct a point mutation with a high efficiency in cultured rodent cells, in the
      body of mice and rats, and in plants. The efficiency of correction in the liver
      of rats was claimed to be as high as 20% after tail-vein injection. However,
      several laboratories have failed to reproduce the high efficiency. METHODS: In
      order to sensitively detect and measure sequence changes by the chimeric
      oligonucleotides, we used Muta Mouse, a transgenic mouse system for mutation
      detection in vivo. It carries, on its chromosome, multiple copies of the lambda
      phage genome with the lacZ(+) gene. Two chimeric oligonucleotides were designed
      to make a point mutation at the active site of the LacZ gene product. They were
      injected into the liver with HVJ liposomes, which were demonstrated to allow
      reliable gene delivery. One week later, DNA was extracted from the liver, and
      lambda::lacZ particles were recovered by in vitro packaging. The lacZ-negative
      phage was detected by selection with phenyl-beta-D-galactoside. RESULTS: The
      mutant frequency of the injected mice was at the same level as the control mouse
      (approximately 1/10000). Our further restriction analysis and sequencing did not
      detect the designed mutations. CONCLUSIONS: Gene correction frequency in mouse
      liver by these oligonucleotides was shown to be less than 1/20000 in our assay
      with the Muta Mouse system.

PMID- 15459967
TI  - Adenoviral vectors expressing fusogenic membrane glycoproteins activated via
      matrix metalloproteinase cleavable linkers have significant antitumor potential
      in the gene therapy of gliomas.
AB  - BACKGROUND: Fusogenic membrane glycoproteins (FMG) such as the gibbon ape
      leukemia virus envelope (GALV) glycoprotein are potent therapeutic transgenes
      with potential utility in the gene therapy of gliomas. Transfection of glioma
      cell lines with FMG expression constructs results in fusion with massive syncytia
      formation followed by cytotoxic cell death. Nevertheless, ubiquitous expression
      of the GALV receptor, Pit-1, makes targeting desirable in order to increase the
      specificity of the observed cytopathic effect. Here we report on use of matrix
      metalloproteinase (MMP)-cleavable linkers to target the cytotoxicity of FMG
      expressing adenoviral vectors against gliomas. METHODS: Replication-defective
      adenoviruses (Ad) were constructed expressing the hyperfusogenic version of the
      GALV glycoprotein linked to a blocking ligand (C-terminal extracellular domain of
      CD40 ligand) through either an MMP-cleavable linker (AdM40) or a non-cleavable
      linker (AdN40). Both viruses also co-expressed the green fluorescent protein
      (GFP) via an internal ribosomal entry site. RESULTS: The glioma cell lines U87,
      U118, and U251 characterized by zymography and MMP-2 activity assay as high,
      medium and low MMP expressors, respectively, the MMP-poor cell lines TE671 and
      normal human astrocytes were infected with AdM40 and AdN40 at different
      multiplicities of infection (MOIs) from 1-30. Fusion was quantitated by counting
      both number and size of syncytia. Infection of these cell lines with AdN40 did
      not result in fusion or cytotoxic cell death, despite the presence of infection,
      as demonstrated by GFP positivity, therefore indicating that the displayed CD40
      ligand blocked GALV-induced fusion. Fusion was restored after infection of glioma
      cells with AdM40 at an MOI as low as 1 to an extent dependent on MMP expression
      and coxsackie adenovirus receptor (CAR) expression in the specific cell line.
      Western immunoblotting demonstrated the presence of the cleaved CD40 ligand in
      the supernatant of fused glioma cells. Use of the MMP inhibitors 1,10
      phenanthroline and N-hydroxy-5,5-dimethylpiperazine-2-carboxamide completely
      abolished AdM40-induced fusion, while the non-specific serine protease inhibitor
      soybean trypsin inhibitor did not affect it, thus demonstrating specificity of
      the observed effect. Intratumoral treatment of BalbC/nude mice bearing
      subcutaneous U87 glioma xenografts with AdM40 at a total dose of 1.2 x 10(10)
      plaque-forming units (pfu) resulted in statistically significant tumor regression
      as compared with control animals either treated with AdN40 (p = 0.01) or
      untreated animals (p = 0.01). Treatment with AdM40 also resulted in survival
      improvement as compared with AdN40-treated animals (p = 0.006) or untreated
      animals (p = 0.001). Histopathologic examination of treated tumors demonstrated
      extensive syncytia formation. CONCLUSIONS: Our data indicate that AdM40, a
      replication-defective adenovirus expressing the GALV fusogenic glycoprotein,
      attached to a blocking ligand via an MMP-cleavable linker, can target the
      cytotoxicity of GALV in MMP-overexpressing glioma lines and xenografts, and
      maintain significant antitumor activity both in vitro and in vivo. Given the high
      frequency of MMP overexpression in gliomas, AdM40 represents a potentially
      promising agent in the gene therapy of these tumors.

PMID- 15459968
TI  - Unmodified oligodeoxynucleotides require single-strandedness to induce targeted
      repair of a chromosomal EGFP gene.
AB  - BACKGROUND: A number of genetic defects in humans are due to point mutations in a
      single, often tightly regulated gene. Genetic treatment of such defects is
      preferably done by correcting only the altered base pair at the endogenous locus
      rather than by a gene replacement strategy involving viral vectors. Promisingly
      high repair rates have been achieved in some systems with the non-viral approach
      of transfecting chimeric RNA/DNA oligonucleotides (chimeraplasts). However, since
      this technique does not yet perform robustly, several parameters thought to be
      important in oligonucleotide-mediated gene repair were examined. METHODS: A
      series of transgenic HEK-293 cell clones has been established harboring high or
      low copy numbers of a point-mutated 'enhanced green fluorescent protein' (EGFP)
      gene as the target. At the level of single living cells, repair efficiencies were
      measured by fluorescence-activated cell sorting (FACS) regarding topology (single
      stranded, double-stranded), exonuclease protection (four phosphorothioate
      linkages at both ends), polarity (sense, antisense), and length (13mer, 19mer,
      35mer, 69mer) of the oligonucleotide. RESULTS: When targeting chromosomal loci,
      up to 0.2% corrected cells were obtained with single-stranded unmodified
      oligodeoxynucleotides, whereas a chimeraplast, its DNA analogue, and double
      stranded DNA fragments were practically non-functional. Correction efficiencies
      correlated with target gene copy numbers. Modifying exonuclease resistance,
      polarity or length of single-stranded oligodeoxynucleotides did not enhance
      repair efficacy above the sub-percentage range. CONCLUSIONS: Successful
      chromosomal reporter gene repair in HEK-293 cells required an
      oligodeoxynucleotide to be single-stranded. In concert with the gene copy number
      correlation, functional interaction between the repair molecule and the target
      site seems to be one bottleneck in targeted gene repair.

PMID- 15459969
TI  - Spectrum of PTCH mutations in Italian nevoid basal cell-carcinoma syndrome
      patients: identification of thirteen novel alleles.
AB  - The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant genetic
      disease characterized by numerous basal cell carcinomas, odontogenic keratocysts
      of the jaws, palmar and plantal pits, skeletal abnormalities, and calcification
      of the falx cerebri. The gene responsible for this syndrome is the PTCH tumor
      suppressor gene encoding for the sonic hedgehog receptor. In this paper, we
      report thirteen novel mutations identified in the first screening of NBCCS
      patients in Italy. Except for p.T230P and p.F505_L506delinsLR, all the other
      mutations are predicted to determine a premature truncation of the protein.

PMID- 15459970
TI  - Homeologous recombination between AluSx-sequences as a cause of hemophilia.
AB  - Although large deletions from the coagulation factor VIII gene, F8, are
      responsible for 5% of severe hemophilia A (seHA), few of them have been fully
      characterised. A detailed description of a large partial deletion of the F8
      caused by unequal recombination between homeologous AluSx-derived sequences is
      presented. The proband, a case of isolated hemophilia A with a high inhibitor
      titre (5700 BU), showed a consistent absence of PCR-amplification of exons 4 to
      10, EX4_EX10del. Two approaches were used to narrow down the deletion
      breakpoints: a direct physical analysis based on PCR (that additionally permits
      carrier detection in the family); and, under the hypothesis that the mutation
      resulted from homologous recombination, sequence alignments of F8 intron 3 and
      10. Both approaches indicate an unequal crossing over (CO) between two Alu
      related sequences. Both elements involved were derived from the AluSx-subfamily
      consensus and demonstrate 86% sequence identity (with only single-base
      mismatches), with three gaps (of 2, 3 and 14-bases) and two main tracts of
      perfectly homologous sequence (28 and 24-bp). The short stretch of intron 10
      embedded into intron 3 sequence, linked to the CO, represents a typical hallmark
      of homologous recombination (double-strand break repair model). A detailed
      description of EX4_EX10del mutation is c.[338+3485delins1687+2223_1687+2225;
      338+3551_1687+2291 del]. The common involvement of unequal homologous
      recombination mediated by repetitive elements allowed us to suggest that our
      experimental design (based on intron sequence alignments) may be successfully
      applied to rearrangements involved in other X-linked inherited diseases. Like
      other Alu-rich genes throughout the human genome, Alu-mediated homologous
      recombination in F8 may be an important cause of hemophilia by promoting large
      DNA deletions.

PMID- 15459971
TI  - A point mutation in the lariat branch point of intron 6 of NPC1 as the cause of
      abnormal pre-mRNA splicing in Niemann-Pick type C disease.
AB  - The lariat branch point sequence (BPS) is crucial for splicing pre-mRNA even if
      BPS mutations have infrequently been reported in human disease. In two siblings
      with Niemann-Pick type C (NPC) disease we identified two mutations of the NPC1
      gene: i) one in exon 20 (c.2932C>T) (p.R978C) previously reported in NPC
      patients; ii) the other (c.882-28A>G) unreported, in the highly conserved
      adenosine of a putative lariat BPS of intron 6. Using RT-PCR we found that,
      besides the normally spliced mRNA, patients' fibroblasts contained minute amounts
      of an mRNA devoid of exon 7. The exon 6--exon 8 junction in this mRNA causes a
      frameshift and a premature stop codon, predicted to result in a truncated
      protein. To assess the effect of c.882-28A>G mutation we constructed two
      minigenes (wild type and mutant), spanning from intron 5 to intron 8, which were
      inserted into a pTarget vector and transfected in COS1 cells. The wild type
      minigene generated an mRNA of the expected size and sequence; the mutant minigene
      generated only an mRNA devoid of exon 7. This is the first example of a splicing
      defect due to a mutation in the lariat BPS in an intron of NPC1 found in NPC
      patients.

PMID- 15459972
TI  - Novel and recurrent mutations clustered in the von Willebrand factor A domain of
      MATN3 in multiple epiphyseal dysplasia.
AB  - Multiple epiphyseal dysplasia (MED) is a common skeletal dysplasia characterized
      by joint pain and stiffness, delayed and irregular ossification of epiphyses, and
      early-onset osteoarthritis. Six genes responsible for MED have been identified,
      including COMP, COL9A1, COL9A2, COL9A3, DSTDT and MATN3. MATN3 encodes matrilin
      3, a cartilage-specific extracellular matrix protein. To date, seven different
      MATN3 mutations have been identified; all are located within the beta-sheet
      regions of the von Willebrand factor type A (vWFA) domain, which is encoded by
      exon 2. We examined MATN3 mutations in27 Japanese MED patients who were possibly
      autosomal dominant inheritance and had been excluded for COMP mutations. Ten of
      them had a positive family history. We examined all eight exons of MATN3 by PCR
      and direct sequencing from genomic DNA. We have identified four missense
      mutations in eight unrelated families; two are novel, and two have been
      characterized previously. Like previously characterized MATN3 mutations, those
      identified in this study are clustered within exon 2, specifically in and around
      the 2nd beta-sheet region of the vWFA domain (aa. 120-127). Contrary to the
      previous assumption that the MATN3 mutation in MED is confined to the beta-sheet
      regions, one novel mutation (p.F105S) is located outside the beta-sheet region,
      within an alpha-helix region.

PMID- 15459973
TI  - Mutation analysis of NR2E3 and NRL genes in Enhanced S Cone Syndrome.
AB  - Ten new and seventeen previously reported Enhanced S Cone Syndrome (ESCS)
      subjects were used to search for genetic heterogeneity. All subjects were
      diagnosed with ESCS on the basis of clinical, psychophysical and/or
      electroretinography testing using published criteria. Mutation analysis was
      performed on the NR2E3 nuclear receptor gene by single strand conformation
      analysis and direct sequencing, which revealed either homozygous (N=13) or
      compound heterozygous (N=11) mutations in 24 subjects (89%), heterozygous
      mutations in 2 subjects (7%) and no mutations in 1 subject (4%). Fifteen
      different mutations were identified, including six not previously reported. The
      subject (Patient A) with no detected NR2E3 mutation had features not usually
      associated with ESCS, in particular moderate rod photoreceptor function in
      peripheral retina and an abnormally thick retinal nerve fibre layer. Mutation
      analysis of the NRL, CRX, NR1D1 and THRB genes in this individual revealed a
      heterozygous one base-pair insertion in exon 2 of the NRL gene, which results in
      a predicted truncation of the NRL protein. Loss-of-function NRL alleles have not
      been described previously in humans, but since the same mutation was present in
      unaffected family members, it raises the possibility that the abnormal ESCS
      phenotype in Patient A may result from a digenic mechanism, with a heterozygous
      NRL mutation and a mutation in another unknown gene.

PMID- 15459974
TI  - ABCC6 mutations in Italian families affected by pseudoxanthoma elasticum (PXE).
AB  - Pseudoxanthoma elasticum (PXE) is a genetic disorder, characterized by cutaneous,
      ocular and cardiovascular clinical symptoms, caused by mutations in a gene
      (ABCC6) that encodes for MRP6 (Multidrug Resistance associated Protein 6), an ATP
      binding cassette membrane transporter. The ABCC6 gene was sequenced in 38
      unrelated PXE Italian families. The mutation detection rate was 82.9%. Mutant
      alleles occurred in homozygous, compound heterozygous and heterozygous forms,
      however the great majority of patients were compound heterozygotes. Twenty-three
      different mutations were identified, among which 11 were new. Fourteen were
      missense (61%); five were nonsense (22%); two were frameshift (8.5%) and two were
      putative splice site mutations (8.5%). The great majority of mutations were
      located from exon 24 to 30, exon 24 being the most affected. Among the others,
      exons 9 and 12 were particularly involved. Almost all mutations were located in
      the intracellular site of MRP6. A positive correlation was observed between
      patient's age and severity of the disorder, especially for eye alterations. The
      relevant heterogeneity in clinical manifestations between patients with identical
      ABCC6 mutations, even within the same family, seems to indicate that, apart from
      PXE causative mutations, other genes and/or metabolic pathways might influence
      the clinical expression of the disorder.

PMID- 15459975
TI  - Fine mapping and identification of a candidate gene SSH1 in disseminated
      superficial actinic porokeratosis.
AB  - Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal
      dominant chronic keratinization disorder, characterized by multiple superficial
      keratotic lesions surrounded by a slightly raised keratotic border. Thus far,
      although two loci for DSAP have been identified, the genetic basis and
      pathogenesis of this disorder have not been elucidated yet. In this study, we
      performed a genome-wide linkage analysis in three Chinese affected families and
      localized the gene in an 8.0 cM interval defined by D12S330 and D12S354 on
      chromosome 12. Upon screening 30 candidate genes, we identified a missense
      mutation, p.Ser63Asn in SSH1 in one family, a frameshift mutation,
      p.Ser19CysfsX24 in an alternative variant (isoform f) of SSH1 in another family,
      and a frameshift mutation, p.Pro27ProfsX54 in the same alternative variant in one
      non-familial case with DSAP. SSH1 encodes a phosphatase that plays a pivotal role
      in actin dynamics. Our data suggested that cytoskeleton disorganization in
      epidermal cells is likely associated with the pathogenesis of DSAP.

PMID- 15459977
TI  - Nutrition and gene regulation. Proceedings of a symposium held at Harvard Medical
      School. March 13-14, 2003. Boston, Massachusetts, USA.

PMID- 15459978
TI  - Festschrift in honor of the 70th birthday of Dr. Samuel H. Barondes.

PMID- 15459980
TI  - Sagittal profile of the spine prominent part of the pelvis.

PMID- 15459981
TI  - [Epidemiology and Prevention of kala-azar in China].

PMID- 15459982
TI  - Regulation of cationic amino acid transport: the story of the CAT-1 transporter.
AB  - The discovery of the function of the receptor for the ecotropic retrovirus as a
      membrane transporter for the essential amino acids lysine and arginine was a
      landmark finding in the field of molecular nutrition. This finding indicated that
      cationic amino acid transporters (CATs) act pathologically as viral receptors.
      The importance of this transporter was further supported by knockout mice that
      were not viable after birth. CAT-1 was the first amino acid transporter to be
      cloned; several other CATs were later characterized biochemically and
      molecularly. These transporters mediate the bidirectional transport of cationic
      amino acids, thus supporting important metabolic functions, such as synthesis of
      proteins, nitric oxide (NO) synthesis, polyamine biosynthesis, and interorgan
      amino acid flow. This review briefly describes the advances in the regulation of
      cationic amino acid transport, focusing on the molecular mechanisms that regulate
      the CAT-1 transporter. Of particular interest to this review is the regulation of
      CAT-1 by nutritional stresses, such as amino acid availability. The studies that
      are reviewed conclude that the CAT-1 gene is essential for cell survival during
      stress because it allows cells to resume growth as soon as amino acids become
      available.

PMID- 15459983
TI  - Must we preserve life?

PMID- 15459984
TI  - The International AIDS Conference in Bangkok: two views.

PMID- 15459985
TI  - Artificial feeding--'The Pope's argument rests on human rights. Why can't we see
      that?'.

PMID- 15459986
TI  - At the bedside.

PMID- 15459987
TI  - Price to pay: the misuse of embryos.

PMID- 15459988
TI  - Beyond politics--the strange saga of the President's Council on Bioethics.

PMID- 15459989
TI  - To correct the record: the continuing, troubling, inaccurate accounts of my case.

PMID- 15459990
TI  - The protection of the human embryo in vitro. Report by the Working Party of the
      Human Embryo and Fetus.

PMID- 15459991
TI  - Bioethics and the determination of personhood.
AB  - In today's technological world, humanity continuously surpasses the limits set by
      previous achievements. Although evidence of such progress exists in several
      fields of study, one clearly sees this in the medical and biotechnological
      fields. Despite the countless opportunities for longer, more productive lives,
      medicine and science have regressed in their conception of the human person. In
      an effort to overcome any moral and legal ramifications that research and medical
      practices entail, physicians and researchers have come to reduce personhood to
      only a matter of biological qualities and functioning. This essay attempts to
      show, first of all, the classical Christian understanding of the person,
      currently held by the Orthodox Church. It then looks at three fields of
      bioethical discussion; namely, abortion, brain death, and human embryonic
      cloning, and shows how each issue reduces the human person to his or her
      biological components. The essay concludes by suggesting a return to an
      understanding of personhood based on personal and communal levels of
      relationships.

PMID- 15459992
TI  - Medically assisted procreation and the right to found a family.

PMID- 15459993
TI  - Soap opera and winter itch: synthetic detergent bars (syndets) provide superior
      mildness compared with soaps.

PMID- 15459994
TI  - Prevention of postoperative nausea and vomiting.

PMID- 15459995
TI  - But what about mercury in vaccinations?

PMID- 15459996
TI  - Airway obstruction in chronic obstructive pulmonary disease.

PMID- 15459997
TI  - Management of chronic obstructive pulmonary disease.

PMID- 15459998
TI  - Management of chronic obstructive pulmonary disease.

PMID- 15459999
TI  - Management of chronic obstructive pulmonary disease.

PMID- 15460000
TI  - Open mesh versus laparoscopic mesh hernia repair.

PMID- 15460001
TI  - Open mesh versus laparoscopic mesh hernia repair.

PMID- 15460002
TI  - [A study of bronchial asthma with Chinese characteristics].

PMID- 15460003
TI  - [Some explanations for newly revised Chinese guideline of prevention and
      management of bronchial asthma].

PMID- 15460004
TI  - [The control of transmission of AIDS vis blood transfusion and intravenous drug
      abuse in China].

PMID- 15460005
TI  - [Progress in the study of prevention and control of Brucellosis in China in last
      50 years].

PMID- 15460006
TI  - [Progress in the prevention and control of neonatal tetanus in China].

PMID- 15460007
TI  - [Study of prevention and control of primary hypertension].

PMID- 15460008
TI  - [Current status in the prevention and control of dengue fever in China].

PMID- 15460009
TI  - [Prevention and control of malaria in China, in last 50 years].

PMID- 15460010
TI  - [Progress in the epidemiologic study of weil's disease in China in recent 50
      years].

PMID- 15460011
TI  - [Rodent control in China in recent 50 years].

PMID- 15460012
TI  - [Study on the oral helicobacter pylori infection].

PMID- 15460013
TI  - Avian influenza--situation in Viet Nam as of 18 August 2004.

PMID- 15460014
TI  - Onchocerciasis (river blindness). Report from the thirteenth InterAmerican
      Conference on Onchocerciasis, Cartagena de Indias, Colombia.

PMID- 15460015
TI  - [Lovastatin effect on ergosterol production and growth of Tolypocladium inflatum
      106].
AB  - The effect of lovastatin on Tolypocladium inflatum 106 was studied. The strain
      was shown to be highly sensitive to lovastatin when its MIC was determined by the
      agar diffusion method and under submerged conditions that was considered possible
      to use the strain as a test culture in screening of new natural compounds with
      hypolipidemic action and to study its specificity. It was demonstrated that the
      effect of lovastatin on ergosterol synthesis in T. inflatum 106 was of specific
      dose-dependent polymodal nature.

PMID- 15460016
TI  - [Experimental study on the effect of low molecular DNA from salmon milt on
      hemopoiesis].
AB  - Biological activity of low molecular DNA isolated from salmon milt was studied.
      When administered subcutaneously to mice with with acute experimental radiation
      disease in a course dose of 10 mg/kg, it showed a therapeutic effect, stimulated
      hemopoiesis, increased the survival rate and the average life span of the
      animals. Moreover, its marked effect on the humoral immunity was observed.

PMID- 15460017
TI  - [Investigation of cell wall components in actinomycin D resistant Staphylococcus
      aureus].
AB  - Cell walls in 2 strains of Staphylococcus aureus 209P, i.e. actinomycin D
      susceptible and resistant ones were comparatively investigated. The resistant
      cells contained much more wall material per a unit of the biomass weight vs the
      susceptible strain cells, that conformed to thickening of the resistant cell
      walls detected by electron microscopy and a sharp increase of their electron
      density. Investigation of peptidoglycans and teichoic acids did not reveal any
      significant alterations in the structure of the wall components in the
      actinomycin D resistant cells. Only some increase of glucosamine in the
      peptidoglycan fraction of the resistant cells vs the susceptible ones was
      observed. It was shown that preparations of the resistant cell walls and
      peptidoglycan isolated from the resistant cells were able to bind somewhat lower
      quantities of actinomycin D vs the analogous preparations of the susceptible
      cells. The significant decrease of the antibiotic binding by live cells of the
      resistant strain probably slightly depended on the structure characteristics of
      the main wall components. The barrier properties of the walls in resistant
      staphylococci are most likely defined by the wall thickening and consolidation
      while adapting to actinomycin D.

PMID- 15460018
TI  - [Experimental basis for the use of new dosage forms of doxorubicin for correction
      of its hepatotoxic, prooxidant and immunosuppressory effects].
AB  - The study was aimed at design of new dosage forms of doxorubicin (films,
      erythrocyte vehicles) for correction of its hepatotoxic, prooxidant and
      immunosuppressory effects. The experiments were performed on Wistar rats with the
      use of doxorubicin of Lens-Pharm (Moscow) and auxiliary substances meeting the
      requirements of the standards. Technology for preparation of doxorubicin
      entrapped films was developed and the optimal polymer for the vehicle was
      recommended, i.e. oxypropylmethylcellulose Methocel 65 Hg 50 providing
      preservation of the antimicrobial activity. Conditions for storage of the
      antibiotic-entrapped films were determined. The main qualitative indices of the
      antibiotic-entrapped films were shown to be stable during the storage for 12
      months. Erythrocyte-vehicles with entrapped doxorubicin were prepared. Antibiotic
      free erythrocyte vehicles were found to preserve their ability to entrap
      doxorubicin for 9 days and the doxorubicin-entrapped erythrocyte vehicles were
      stable for 48 hours. A procedure for spectrophotometric qualitative evaluation of
      doxorubicin entrapping into the films and erythrocyte vehicles was developed. It
      was observed that administration of doxorubicin immobilized in the films had a
      stabilizing effect on the immunity status, the level of lipid peroxidation, the
      potency of the antioxidant system, cytolysis and cholestasis. Administration of
      the doxorubicin entrapped in the erythrocyte vehicles stimulated the body immune
      response, normalized the indices of the lipid peroxidation--antioxidant system
      and the state of the hepatic cells in the laboratory animals infected by
      staphylococci.

PMID- 15460019
TI  - [Antimicrobial activity of new original 2-aryliden-6-furfuryliden cyclohexanones
      and hexahydroindazoles on their basis].
AB  - Antimicrobial activity of 25 new original 2-aryliden-6-furfuryliden
      cyclohexanones and hexahydroindazoles based on them was studied. The majority of
      the compounds had low or moderate activity against the test cultures of
      Staphylococcus spp., Pseudomonas aeruginosa, Proteus spp. and Escherichia coil.
      Compound XIX (2,3-diphenyl-7-(5-nitrofurfuryliden)-3,3a,4,5,6,7
      hexahydroindazole) with high antistaphylococcal activity was selected among
      several 2-aryliden-6-furfuryliden cyclohexanones and hexahydroindazoles. The
      activity of compound XIX was tested with the use of 105 clinical isolates of
      staphylococci. Comparative antistaphylococcal activity of compound XIX,
      furazolidone and sodium cefotaxime against the isolates was estimated. The impact
      of the microbial load, pH of the nutrient medium and the presence of 1%, 5% or
      10% of serum or blood in the medium on the antimicrobial activity of compound XIX
      was evaluated. The results are in favour of further research on compound XIX as a
      potential agent of etiotropic therapy for staphylococcal infection.

PMID- 15460020
TI  - [Dynamics of Streptococcos pneumoniae antibiotic resistance extension in Moscow
      in 1998-2003].
AB  - During the 6-year observation period from 1998 to 2003 in Moscow there was
      recorded in 2000-2001 a decrease in the emergence of Streptococcos pneumoniae
      resistance to many antibacterials, while during the following years the
      respective index increased. The above dynamics in the resistance emergence was
      likely due to a decrease in the use of antibiotics in 1998-1999. In 2003 the rate
      of resistance to penicillin was 18.6%, 0.4 and 2.1% of the isolates were
      resistant to amoxicillin and cefotaxime respectively, the rate of resistance to
      erythromycin reached 19%, 65.4% of the resistant strains showed M phenotype. High
      rates of resistance were as well observed with respect to tetracycline (40.1%),
      co-trimoxazole (29.1%) and chloramphenicol (18.6%). Resistance to levofloxacin
      and moxifloxacin was detected only in rare strains.

PMID- 15460021
TI  - [Large intestine dysbacteriosis and therapy efficacy in patients with respiratory
      tract tuberculosis in sanatoria].
AB  - Long-term chemotherapy of tuberculosis leads to dysbacteriosis of the large
      intestine, that significantly decreases tolerance of tuberculosis drugs, provokes
      persistence of tuberculosis intoxication and retards involution of tuberculosis
      process in the lungs. Recovery of the bifidoflora and lactoflora due to the use
      of an original sour-milk drink developed by the authors was stated in 65 and 55%
      of the patients respectively. Moreover, it promoted higher tolerance of the
      chemotherapeutics since its composition includes amino acids, vitamins B, C, D
      and E, enzymes and microelements. It should be indicated that the drink was used
      simultaneously with the chemotherapy and did not require its discontinuation.
      Therefore, it is recommended that the scheme of the treatment of patients with
      pulmonary tuberculosis in sanatoria should include corrigating agents and in
      particular probiotics containing live bifido- and lactobacteria having no
      contraindications and side effects, and providing elimination of intestinal
      dysbacteriosis.

PMID- 15460022
TI  - [Chronic treatment with GABA A receptor blockers increases efficacy of GABAergic
      synaptic transmission in rat hippocampal neuron cultures].
AB  - It has been proposed to consider plasticity in neuronal network as occurring in
      two forms: use-dependent plasticity which modifies the network properties, and
      homeostatic plasticity which may counteract use-dependent changes. Chronic block
      of some of transmitter receptors is often used as a model for studying
      homeostatic plasticity. We studied whether chronic block of GABAA receptors can
      affect GABAergic transmission. Using whole-cell voltage clamp recording and local
      extracellular stimulation we investigated evoked inhibitory postsynaptic currents
      (IPSCs) in cultured rat hippocampal neurons grown in the presence of GABAA
      receptor antagonist--bicuculline (20mM) and in control conditions. Cell for both
      control and pretreated cultures were obtained from same dissection and were grown
      in parallel. We compared the amplitudes of the evoked IPSC, the reversal
      potentials of the responses IPSC coefficient of variation and depression evoked
      by paired stimulation. Chronic bicuculline treatment did not significantly affect
      the paired-pulse depression (PPD) and IPSC reversal potentials. In contrast we
      found that amplitude of evoked IPSCs was increased about two times in cultures
      treated with bicuculline. However, IPSC coefficients of variation were not
      significantly different. We conclude that chronic block of GABAA receptors
      enhances efficacy of GABAergic synaptic transmission in rat hippocampal cell
      cultures and this effect is likely to postsynaptic mechanism(s) because IPSC
      increase was not accompanied with changes of IPSC coefficient of variation. A
      possibility that the effect of chronic block of GABAA receptors on GABAergic
      transmission is mediated by neurotrophin BDNF is discussed.

PMID- 15460023
TI  - [Effect of synaptic transmission blockade and hypoglycemia on neuron impulse
      activity in cultured rat hippocampal neurons].
AB  - Spontaneous neuronal activity was studied in rat hippocampal cell cultures using
      patch clamp technique in cell-attached or loose-patch configuration. It was found
      that in spite of relatively low average frequency (1-2 Hz) of neuronal activity
      in the cell cultures, neurons often fire doublets or triplets of action
      potentials with interspike interval of 60 ms and less. Interspike interval
      histograms were substantially better fitted by double exponential decay functions
      than by single exponential ones. On average, estimated decay time constant for
      the fits were tau1 approximately 36, ms and tau2 approximately 1000 ms
      respectively. Spontaneous neuronal firing to a large extent depended on
      glutamatergic excitation and GABA(A)ergic inhibition: a blocker of AMPA/kainate
      receptor CNQX (10 microM) either substantially decreased or completely blocked
      spontaneous action potentials; a blocker of GABA(A) receptors bicuculine (10
      microM) increased neuronal firing. Effect of glucose deprivation on action
      potential frequency was also studied. It was found that glucose deprivation
      reduces AP frequency to 25% of control. Taken together, these results support an
      idea that hypoglycaemia alters synaptic transmission in hippocampus.

PMID- 15460024
TI  - Estimating transmitter release rates and quantal amplitudes in central synapses
      from postsynaptic current fluctuations.
AB  - Several approaches recently introduced to analyze release rates in central
      synapses advanced our understanding of synaptic neurotransmission, however,
      leaving many questions still unresolved. In this work we present evidence that a
      new method recently developed by Sakaba and Neher to study neurotransmission in
      calyx of Held, a giant glutamatergic synapse, could be also applied for
      estimating release rate functions and averaged quantal sizes in small central
      synapses. By means of different simulation approaches applied to reproduce
      GABAergic neurotransmission in the hippocampus we have shown that possible
      problems with a spatial voltage clamp which can occur in synaptic connections
      distributed over a large area of dendritic tree are not crucial for applicability
      of the method when synapses are compactly distributed or located proximally and
      when release rates are below 1 ms(-1). In another set of simulations we have also
      shown that at above mentioned release rates desensitization and/or saturation of
      postsynaptic GABAA receptors does not prevent accurate estimates of release rate
      and averaged quantal size. Thus, we conclude that the new approach based on
      analysis of fluctuations of postsynaptic currents under conditions of stationary
      release or moderately nonstationary conditions might be applicable to studies of
      small central synapses.

PMID- 15460025
TI  - [Changes of intracellular calcium-regulating mechanisms of primary and secondary
      sensory neurones in periferal inflammation].
AB  - Here we summarize the results of experimental investigation of changes in
      intracellular calcium homeostasis in mice and rat primary (dorsal root ganglia,
      DRG) and secondary (dorsal horn, DH) sensory neurons under carrageenan-induced
      periferal inflammation. A decrease in a calcium accumulation in both
      inositoltriphosphate- and caffeine-sensitive endoplasmic reticulum calcium stores
      has been detected in primary sensory neurons under condition of peripheral
      inflammation. We have also shown a decrease in the caffeine-induced calcium
      release in dorsal horn neurons of inflamed rat as compared to control ones.
      Decrease in the Ca2+ -accumulating properties of mitochondria has been
      demonstrated in both DRG and DH neurons with carrageenan-induced inflammation as
      compared with neurons of control animals. We conclude that changes in Ca2+ 
      regulating structures of primary and secondary sensory neurons could possibly
      lead to alterations in the transmission of nociceptive signals during
      inflammation.

PMID- 15460026
TI  - [Electrophysiological properties of inhibitory neurones in cultured dissociated
      hippocampal cells].
AB  - Electrophysiological properties of inhibitory (GABAergic) neurones were studied
      in dissociated hippocampal culture using simultaneous whole cell recordings from
      pairs of monosynaptically coupled neurons. Reliable identification of GABAergic
      neuron was performed by presence of monosynaptic inhibitory currents at
      postsynaptic cell in response to action potentials at stimulated cell. It was
      shown that GABAergic neurons in hippocampal culture are divided in two groups by
      their firing characteristics: first type generates action potentials at high
      frequency in response to injection of current (duration 0.5 s)--fast-spiking
      neurons (FS), cells from second type has no ability for high-frequency action
      potential generation--regular spiking neurons (RS). These two groups were
      distinguished by kinetic characteristics of action potentials, adaptation
      characteristics during continuous generation of action potentials and inhibitory
      effect making on postsynaptic cell. Application of potassium channel blocker 4-AP
      to somas of FS neurons in concentration, which selectively inhibits Kv3 potassium
      channels evoked reversible changes in kinetic of action potentials, frequency and
      adaptation characteristics during continuous generation of action potentials. It
      was concluded that there is hight level of expression of Kv3 potassium channels
      in the first group of neurons.

PMID- 15460027
TI  - Activation of ryanodine receptors influences the paired-pulse depression in
      cultured rat hippocampal neurons.
AB  - Role of intraterminal calcium stores in modulation of short-term plasticity of
      evoked inhibitory postsynaptic currents (IPSCs) was studied in synaptically
      connected cultured hippocampal neurons using patch-clamp technique in whole-cell
      configuration. Currents were induced by voltage stimulation which were applied
      externally to presynaptic fiber. Paired stimuli resulted in paired-pulse
      depression (n=18) or facilitation (n=7) of the second IPSC at interpulse
      intervals 150 and 500 ms. Calcium release from intracellular calcium stores was
      activated by local application of caffeine and ryanodine, ryanodine receptor
      agonists. One of the characteristics of short-term plasticity, the pair-pulsed
      ratio (ratio of amplitudes of second IPSC to first IPSC), decreased during
      addition of ryanodine (50 nM) from 0.79 +/- 0.02 to 0.71 +/- 0.04 (n=10). This
      change was observed only for cells that demonstrated pair-pulsed depression. We
      also studied the influence of caffeine and ryanodine on spontaneous currents.
      Attenuation of the mean amplitude to 0.71 +/- 0.06 and frequency to 0.42 +/- 0.08
      (n=7) of spontaneous IPSCs was observed during application of caffeine (10 mM).
      Upon ryanodine application the mean amplitude did not change but frequency of
      spontaneous events decreased to 0.74 +/- 0.09 (n=12). The amplitudes of currents
      evoked by fast local application of gamma-aminobutyric acid (GABA 100 mM) were
      diminished in the presence of caffeine (10 mM) to 0.59 +/- 0.03 (n=5) and in the
      presence of ryanodine (50 nM) to 0.56 +/- 0.11 (n=7). Thus we conclude that
      endoplasmic reticular calcium stores are able to modulate synaptic transmission
      from both presynaptic (in assumption that short-term plasticity and spontaneous
      activity are believed to have presynaptic nature) and postsynaptic (since GABA
      receptors are situated on postsynaptic cell) sides.

PMID- 15460028
TI  - [Changes in extracellular K+ concentration modulate properties of voltage
      dependent K+ channel conductance in PC-12 cells].
AB  - The complex processing and integration of signals observed in neurons are
      facilitated by the diverse range of gating properties of the ion channels in this
      cell type, particularly the voltage-gated K+ channels (Kv). A distinctive
      combination of K+ channels endows neurons with a broad repertoire of excitable
      properties and allows each neuron to respond in a specific manner to a given
      input at a given time. The properties of many K+ channels can be modulated by
      second messenger pathways activated by neurotransmitters and other stimuli. K+
      channels are among the most frequent targets of the actions of several signalling
      systems.

PMID- 15460029
TI  - [Effect of dopamine on activity of brain sensory-motor cortex neurons during
      conditioned reflex].
AB  - A changes of background and evoked activity of deep cortical layers neurons and
      latency of the movement in the response to the conditioned stimuli were
      investigated in cats chronical experiments during microelectrode iontophoretic
      local aplication of dopamine, its antagonists and antagonists ofglutamatergic and
      gabaergic transmission. It was shown, that application of dopamine and others
      synapticaly active substances near soma of pyramidal neurons moderately increased
      their background and evoked activity and did not sygnificantly change their
      latency. Application of dopamine antagonists sulpiride and SCH 23390 depressed
      the background and evoked impulse activity and increased the latency of neuronal
      reaction and conditioned movements. These effects were completely removed by the
      aplication of the same antagonists together with dopamine. Dopamine removed the
      depressing influence on the background and evoked impulse activity and latency of
      the conditioned reflexes evoked by application of antagonists of glutamate
      ionotropic and metabotropic transmission (AP-4 and MCPG). The same stabilized
      influences were evoked by the iontophoretic application of GABA antagonist
      bicuculline. It was concluded that effects of dopamine are connected with its
      local inhibitory influences on the inhibitory interneurons and their synaptic
      endings on soma of pyramidal neurons.

PMID- 15460030
TI  - [Alfa-subunit composition of neuronal nicotinic acetylcholine receptors of the
      submucosal plexus in the guinea-pig small intestine].
AB  - The alpha-subunit composition of nicotinic acetylcholine receptors (nAChRs) in
      the submucosal plexus of the guinea-pig ileum were studied using the whole-cell
      patch-clamp technique and affinity-purified antibodies (Abs) against alpha3-,
      alpha4, alpha5 and alpha7-subunits of nAChRs. The independent addition of anti
      alpha3 and anti-alpha5 Abs to extracellular bath solution induced depression of
      the acetylcholine (ACh)-evoked currents by 60% +/- 1.56% and 65% +/- 1.62%
      correspondingly. Successive application of anti-alpha5 Abs in the presence of
      anti-alpha3 Abs did not have any additional blocking effect on ACh-evoked
      currents. Anti-alpha7 Abs evoked depression of Ach-induced currents by 24% +/-
      1.51% in 80% of investigated neurons and by 67% +/- 1.5% in 20% of neurons. The
      addition of anti-alpha4 Abs to extracellular bath solution did not have effect on
      membrane currents of the investigated neurons. Our data provide evidence of
      participation of alpha3-, alpha5 and alpha7-containing receptors in the response
      to ACh. Alpha3- and alpha5-subunits are associated in the same functional nAChRs
      that provide greater part of response to ACh in the most of submucosal neurons.
      However, in some neurones alpha7-containing nAChRs provide greater part of
      response to agonist.

PMID- 15460031
TI  - Functional nicotinic acetylcholine receptors in the neurons of rat intracardiac
      ganglia.
AB  - The alpha subunit composition of nicotinic acetylcholine receptors (nAChRs)
      expressed in the neurons of intracardiac ganglia of the rat was investigated
      using monoclonal and polyclonal antibodies against alpha3, alpha4, alpha5 and
      alpha7 nAChR subunits. The acetylcholine-induced membrane potentials in the
      neurons of the subepicardial plexus isolated from the left atrium of the heart
      were studied by intracellular recording performed in the presence of subunit
      specific nAChR-blocking antibodies applied either separately or in various
      combinations. It was found that intracardiac ganglia neurons express
      alpha3alpha5; alpha7; alpha7(alpha5) and alpha4-containing nAChRs. The neurons
      were heterogeneous as to the nAChR subtypes expressed that possibly indicated
      their functional differences.

PMID- 15460032
TI  - [Single nonselective cation channels activated by muscarinic agonists in smooth
      muscle cells of the guinea-pig small intestine].
AB  - The carbachol-evoked inward cationic current in guinea-pig ileum smooth muscle
      cells is comprised of three types nonselective cationic channels (NSCC) with
      small (10 +/- 2 pS), medium (56 +/- 8pS) and large (135 +/- 14 pS) unitary
      conductance. All three types of NSCC could be activated by external application
      of carbachol as well as by internal application of GTPgS. It was found that
      behavior of carbachol- and GTPgammaS-evoked whole-cell current is mainly
      determined by the properties of medium conductance channels. The U-shaped I-V
      relationship of the whole-cell cationic current at negative potentials range
      arrives from voltage-dependence of its Po of this channel.

PMID- 15460033
TI  - Developmental changes in the distribution of corticosteroid-binding globulin in
      fetal and newborn sheep tissues.
AB  - Developmental changes in immunohistochemical localization of corticosteroid
      binding globulin (CBG) in fetal and newborn sheep tissues were studied. Tissue
      samples have been harvested at days 63-64, 100-103, 125-128 and 142-144 of
      gestation or 2 postnatal days. In the liver, immunoreactive CBG (irCBG) has been
      identified in hepatocytes. The intensity of CBG staining was highest at 63-64th
      gestation days and then was lowered gradually down to negligible level in newborn
      lambs. Within kidney, irCBG was selectively localized to the epithelium of
      proximal and distal convoluted tubules. Its amount in the course of development
      followed a pattern similar to that in the liver. By contrast, fetal sheep lung
      and pancreas demonstrated noticeable rise of irCBG late in gestation. irCBG has
      been detected in respiratory epithelium of tertiary bronchi, bronchioles and
      terminal bronchioles, meanwhile alveoli and other lung tissues were CBG
      immunonegative. In the pancreas, irCBG staining was associated with acinary
      cells, whereas Langerhans islets contained no irCBG at all examined stages of
      pregnancy. Developmental changes in irCBG did not follow reported triphasic
      profile of fetal sheep plasma CBG concentrations thereby showing the existence of
      independent cellular mechanisms regulating CBG level in the tissues.
      Peculiarities of intraorgan distribution and developmental changes in irCBG
      suggest that intracellular CBG may regulate bioavailable cortisol concentrations
      in the sheep tissues during fetal and early postnatal life.

PMID- 15460034
TI  - [A new method of analysis of impulse activity in brain neurons].
AB  - Investigation of impulse activity of hypothalamic neurons is of a great
      importance in attempt to connect the neuronal function with its activity. We have
      proposed an original method of analysis of background and temperature-induced
      impulse activity of thermosensitive neurons from frontal hypothalamus. In acute
      experiments on cats under ketamine anastasia neuronal activity was measured by
      glass microelectrode. Measurements of background neuronal activity was performed
      during 30 s, and post-stimulus activity was measured during 60 s. Computer
      program calculated the mean value of background activity. These results were used
      to create bar graph in the range +/- 100% with time interval 10%. It is suggested
      that the results of analysis of background activity of thermosensitive
      hypothalamic neurons allow interpret the characteristics of functions of
      hypothalamic neurons.

PMID- 15460035
TI  - [Expression of c-fos in the spinal cord after electrical stimulation of low
      threshold afferent fibres of the rat n. gastrocnemius-soleus].
AB  - The specific pattern of c-fos gene expression was evaluated within the lumbo
      sacral spinal cord during 30 min non-noxious stimulation n. gastrocnemius-soleus
      of male Wistar rats. A lot of small and large Fos-immunoreactive (Fos-ir) nuclei
      were located ipsilaterally, mainly in the middle of the neck and base of the
      dorsal horn (layers 5 and 6). Traditionally, these layers are considered to be
      the region of termination of the low-threshold afferent fibers. A few Fos-ir
      neurons were recorded in the intermediate zone (layer 7) and the area around
      central canal (layer 10). The scarce labeled cells were also revealed within the
      marginal zone and substantia gelatinosa of the dorsal horn, i. e. the zones of
      termination of the high-threshold muscle afferents. In conclusion, the revealed
      pattern of c-fos expression in the spinal cord following non-noxious stimulation
      differs from that induced by noxious stimulation. Thus, the pattern of c-fos
      expression in the spinal cord is dependent on the stimulus modality.

PMID- 15460036
TI  - [Combined effect of agonists and antagonists of the membranes channels on
      hemodynamic indices in rats with normal blood pressure and spontaneous
      hypertension].
AB  - It has been investigated the influence of synthesized in Institute of Organic
      Chemistry NA of Science fluorinated Compound "C" on haemodynamic indexes of
      normotensive (Wistar) and hypertensive (SHR) rats. Molecules of Compound 'C'
      contain the blocker of calcium channels foridon and the potassium channels
      activator flocalin. It was shown that separately used foridon (0.5 mg/kg) and
      flocalin (which has dose-depended effect) evoke hypertensive reaction, decreasing
      the total peripheral resistance. They differently affect the systolic blood
      volume (foridon decreases and flocalin increases) but do not change the heart
      rate. Compound "C" (0.5 mg/kg) decreases arterial pressure and total peripheral
      vessels resistance, decreases heart rate and increases systolic blood volume. In
      hypertensive animals these effects were more pronounced in comparison with
      normotensive animals.

PMID- 15460037
TI  - [Induced contractile activity of smooth muscles of the large intestine in rats
      after NO-syntase inhibition].
AB  - NO involvment in the mechanisms of the contractile activity of the smooth muscle
      cells was studied in the colon. The differences in the effects of different
      transmitters on the kinetics of the contractile activity after NOS inhibition
      have been determined.

PMID- 15460038
TI  - [Calcium-dependent programmed cell death in prostate cancer].
AB  - In the present review we describe the major molecular determinants of calcium
      homeostasis in prostate cancer cells and establish their role in the
      transformation to apoptosis-resistant cell phenotypes typical of advanced
      androgen-independent prostate cancer. We show that the hallmark of such
      transformation is complete loss of apoptosis pathway associated with endoplasmic
      reticulum calcium store depletion.

PMID- 15460039
TI  - [Endoplasmic reticulum and regulation of neuromediator release in presynaptic
      terminals].
AB  - Synaptic transmission provides the fundamental mechanisms for integrative
      processes in neuronal networks. Efficacy of synaptic transmission is directly
      controlled by the amount of neurotransmitter released into synaptic cleft. The
      release of the neurotransmitter, in turn, is regulated by several molecular
      cascades expressed in the presynaptic terminal. Activity of these cascades is
      regulated by the concentration of free calcium ions ([Ca2+]i) within the
      presynaptic terminal, and therefore an increase of [Ca2+]i in the presynaptic
      compartment controls neurotransmitter release. Elevation of [Ca2+]i in the
      presynaptic terminal results from Ca2+ entry through the plasmalemmal voltage
      gated calcium channels, however Ca2+ release from the endoplasmic reticulum (ER)
      calcium store may also contribute towards presynaptic [Ca2+]i signals. In this
      review we summarize data supporting the importance of the ER Ca2+ release in
      regulation of neurotransmitter release.

PMID- 15460040
TI  - [Fabrication of custom-made artificial semi-knee joint based on rapid prototyping
      technique: computer-assisted design and manufacturing].
AB  - OBJECTIVE: To design a new custom-made artificial semi-knee joint based on rapid
      prototyping(RP) technique and to explore a method to solve necroses of
      allocartilage in hemi-joint allotransplantation. METHODS: Based on the extracted
      3D contour image of the articular cartilage of femoral condyle, the custom-made
      artificial semi-knee joint was designed with Surfacer 9.0 image processing
      software. The artificial semi-knee joint design used the femoral condylar 3D
      contour of the patient as the outer face and the subchondral bone 3D contour of
      allograft bone as inner face. One dado for medullary nail and two for special
      designing cages which were used to fix the cartilage into the allograft were
      added on the inner face. After being converted into RP data format, the computer
      assisted design was imported into the LPS600 rapid prototyping machine, and the
      prototype was achieved. Furthermore, the prototype could be modified by hand
      according to the design. Then the RP model was used as a positive mould to build
      up a silica gel negative mould, and the negative mould was sent to the factory to
      manufacture Ti-6A1-4V alloy articular cartilage through ordinary mould-melted
      founding process. Finally, the whole metal cartilage was completed after melting
      two special cages on it and polishing it. RESULTS: A new custom-made artificial
      semi-knee joint was made and used to treat a 14-year old patient. The custom-made
      artificial semi-knee joint and the subchondral bone were a perfect match. The
      operative result was satisfactory. The patient could walk 5 weeks after
      operation. The bone healing of the auto-bone and allo-bone was achieved 6 months
      later. A follow-up period lasting 1 year showed that the knee joint played a good
      function. CONCLUSION: The artificial semi-knee joint is a good match for the
      allograft bone and a good idea to solve necroses of allocartilage in hemi-joint
      allotransplantation.

PMID- 15460041
TI  - [Effect of anti-infective reconstituted bone xenograft as primary bone grafting
      on repair of contaminated radius defect in canine].
AB  - OBJECTIVE: To investigate the effect of anti-infective reconstituted bone
      xenograft (ARBX) as primary grafting on repair of a segmental contaminated defect
      in canine radius. METHODS: The contaminated segmental defects of 1.5 cm were made
      in both radius of 8 canine and 1 ml of staphylococal suspension was injected into
      the defect region at a concentration of 5 x 10(6) CFU/ml. ARBX(experimental side)
      or RBX(control side) was implanted into the two sides of the defects respectively
      as primary grafting followed by internal fixation. The results were compared
      between the two grafting materials in repairing the contaminated segmental
      defect. RESULTS: In ARBX side, the defects were repaired completely in 5 cases
      and partially in 1 case, and there existed no osteomyelitis in all cases; while
      in RBX side, the defects were repaired partially in 1 case and were not repaired
      in 5 cases after 6 months of operation, and there existed osteomyelitis in all
      cases. CONCLUSION: Besides its strong osteoinductive and osteoconductive
      activity, ARBX is highly antibacterial and can be used as primary grafting in
      repairing contaminated segmental defects.

PMID- 15460042
TI  - [Anatomical and biomechanical study on scaphoid ring sign of advanced Kienbock's
      disease].
AB  - OBJECTIVE: To demonstrate the anatomical and biomechanical basis of scaphoid ring
      sign in advanced Kienbock's disease. METHODS: The study consisted of two
      sections. The ligaments stabilizing the proximal pole of the scaphoid were
      observed in 5 specimens. Under 12 kg dead weight load through the tendons of the
      flexion carpal radial, the flexion carpal ulnar, the extension carpal radial, and
      the extension carpal ulnar for 5 minutes, the stresses of the scaphoid fossa and
      lunate fossa were measured in the case of neutral, flexion, extension, radial
      deviation and ulnar deviation of the wrist joint under normal and rupture
      conditions respectively by FUJI prescale film and FPD-305E,306E. RESULTS: Based
      on anatomical study, the ligaments stabilizing the proximal pole of the scaphoid
      consisted of the radioscaphocapitate ligament, long radiolunate ligament and
      scapholunate interosseous ligament; and the latter two ligaments restricted
      dorsal subluxation of the proximal pole of the scaphoid. When compared rupture
      condition with normal condition, the scaphoid fassa stress of radial subregion
      was not significantly different (0.90 +/- 0. 43 vs 0.85 +/- 0.15), and the ones
      of palmar, ulnar and dorsal subregions decreased (0.59 +/- 0.20, 0.52 +/- 0.05
      and 0.58 +/- 0. 23 vs 0.77 +/- 0.13, 0.75 +/- 0.08 and 0.68 +/- 0.09) in the case
      of extension; the scaphoid fassa stresses of all subregions increased or had no
      difference in the case of neural, flexion, radial deviation and ulnar deviation.
      The lunate fossa stresses of all subregions increased in the case of neural, and
      the ones of all subregions decreased or had no difference in the case of flexion,
      extension, radial deviation and ulnar deviation. CONCLUSION: Rotary scaphoid
      subluxation should be treated operatively at III B stage of Kienbock's disease to
      avoid traumatic arthritis of the radioscaphoid joint.

PMID- 15460043
TI  - [A comparative study on two different absorbable intramedullary nails in treating
      metacarpal and phalanx fractures].
AB  - OBJECTIVE: To study the effect of two different absorbable intramedullary nails
      in treatment of metacarpal and phalanx fractures. METHODS: From January 2002 to
      December 2002, open reduction and internal fixation were done with two different
      absorbable intramedullary nails in 60 cases of metacarpal and phalanx fractures
      (52 cases of open fractures and 8 cases of closed fractures). The fracture
      locations were metacarpal in 24 cases, proximal phalanx in 22 cases and media
      phalanx in 14 cases. The emergency operation was performed in 47 cases, selective
      operation in 13 cases. Out of 60 patients, 24 were treated with intramedullary
      nails of poly-DL-lactic acid (PDLLA) (PDLLA group), 36 with intramedullary wire
      of PDLLA composed of chitosan(PDLLA+chitosan group). RESULTS: In the PDLLA
      group(n = 24), the rejection occurred in 8 cases 3-4 weeks after operation. PDLLA
      nails were taken out in 6 of the 8 cases after 5-10 days of operation and bone
      healing was achieved 2 months after re-fixation by Kirschner wire; the rejection
      subsided in the other 2 cases after 25 days of conservative treatment, and bone
      fracture healed after 14 weeks. No rejection was observed with primary healing in
      the other 16 cases of the PDLLA group. In PDLLA + chitosan group(n = 36), the
      rejection occurred in 1 case 19 days after operation, but the rejection subsided
      after 3 days of conservative treatment. No rejection was observed in the other 35
      cases with primary healing. All patients were followed up 4-11 months with an
      average of 6 months. No rejection was observed and bone healing was achieved
      during the follow-up. The time of bone healing was 6-16 weeks (8 weeks on
      average). There was statistically significant difference in the curative result
      between two groups(P < 0. 05). Conclusion Intramedullary nail of PDLLA was very
      suitable to fix fractures of metacarpal and phalanx. During the degradation of
      PDLLA, the acidic products can cause rejection. When PDLLA mixed with chitosan,
      PDLLA can not only strengthen the intensity but also neutralize the acidity. So
      the rejection can be decreased. PDLLA intramedullary nails composed of chitosan
      were better than PDLLA intramedullary nails in clinical treatment of metacarpal
      and phalanx fractures.

PMID- 15460044
TI  - [Treatment of old scaphoid fracture with transposition of vascularized periosteal
      flap and internal fixation].
AB  - OBJECTIVE: To introduce an effective method of treating old scaphoid fracture.
      METHODS: From April 1995 to April 2002, 11 patients with old scaphoid fracture
      were treated with transposition of vascularized periosteal flap and internal
      fixation; if necessary, the radial styloid was removed. Out of 11 patients( 8
      males and 3 females, aged from 17 to 46 years), the fracture sites were medial
      scaphoid in 7, the proximal one in 2 and the distal one in 2. The X-ray films
      showed separated fracture lines. The fracture lines were less than 1 mm in 4
      patients and more than 1 mm in 3 patients. Sclerosis of skeleton ends and cystoid
      degeneration occurred in 2 patients, respectively. RESULTS: After a follow-up of
      3 to 24 months, the fracture healing was obtained within 4 months in 9 cases and
      within 6 to 7 months in 2 cases. Internal fixation was taken out 3 months after
      bone healing. The carpal joint pain and weakness vanished in all cases.
      CONCLUSION: Transposition of vascularized periosteal flap and internal fixation
      have many advantages, such as easy dissection, rich blood supply, quick new bone
      formation, short time of fracture healing and satisfactory function recovery of
      carpal joint.

PMID- 15460045
TI  - [Treatment of osteonecrosis of femoral head with free vascularized fibula
      grafting].
AB  - OBJECTIVE: To evaluate the effect of the treatment of necrosis of femoral head
      with the free vascularized fibula grafting. METHODS: From October 2000 to
      February 2002, 31 hips in 26 patients with ischemic necrosis of the femoral head
      were treated with free vascularized fibula graft. Among these patients, 21
      patients (25 hips) were followed up for 6-18 months (12 months on average).
      According to Steinberg stage: II period, 5 hips; III period, 8 hips; IV period,
      12 hips. RESULTS: Among 25 hips, their Harris Hip Score at all satges were
      improved during the follow-up. The symptom of pain diminished or disappeared
      after operation. The patient's ability to work and live was not limited or only
      slightly limited during the follow-up. Radiographic evaluation showed that most
      femoral heads improved (18 hips) or unchanged (6 hips) and only one worsened.
      CONCLUSION: The free vascularized fibular grafting is a valuable method for
      femoral head necrosis. With this method, we can prevent or delay the process of
      the disease.

PMID- 15460046
TI  - [Repair of extensive bone defect of distal femur with free vascularized two
      fibulae transplantation in adults].
AB  - OBJECTIVE: To investigate the treatment of extensive bone defect of distal femur
      caused by various diseases in adults. METHODS: From February 1998 to December
      2002, 6 cases(aged from 19 to 37) of extensive bone defects of distal femur were
      treated with two free vascularized fibulae, whose defects were caused by
      resection of bone tumor, osteomyelitis and trauma. After the resection of distal
      femur and articular surface of tibia, the fibulae were transplanted and fixed
      with screws. And the periosteum of the two fibulae was dissected and sutured with
      each other. RESULTS: The average follow-up time was 3.3 years. Two free
      vascularized fibulae could give more support to the body and the bone union of
      the fibulae was possible when the periosteum was incised and sutured with each
      other. As time went on, both of the medullary canal reunioned to form a new canal
      as a whole, which would make the grafts stronger. CONCLUSION: Autograft with two
      free vascularized fibulae can increase the stability in treating extensive bone
      defect of distal femur, but the union of knee joint will make flexion and
      extension impossible.

PMID- 15460047
TI  - [Intracystic allograft in management of long bone cyst merging pathologic
      fracture].
AB  - OBJECTIVE: To investigate the efficiency of intracystic allograft fixed with bone
      plate and steel plate in management of long bone cyst merging pathologic
      fracture. METHODS: Twelve cases of long bone cysts with pathologic fractures were
      treated from January 1996 to April 2002. The median dimension of the cyst on the
      radiograph was 3. 6 cm x 8.1 cm. We regularly revealed the sites of cysts, cut
      the anterior wall, got cystic membrane away, implanted allo-bone fibula, ulna or
      radius shafts which were defatted and deproteined. The auto-bone and the allo
      bone of all cases were fixed with bone plate and steel plate; external fixation
      was managed for 3 weeks after operation. RESULTS: All incisions achieved primary
      healing. All cases were followed up 2. 7 years on average. According to Capanna's
      standard, 9 cases completely healed, 3 cases basically healed, no cases recurred.
      The function in shoulder joint was slightly limited in 2 cases that cysts were
      located on the upper humerus, while that of the other 10 cases were recovered
      completely. CONCLUSION: Intracystic allograft fixed with bone plate and steel
      plate is safe and effective in management of long bone cyst merging pathologic
      fracture.

PMID- 15460048
TI  - [mRNA expression of activin a and follistatin in rabbit mandibular distraction
      osteogenesis].
AB  - OBJECTIVE: To examine the mRNA expression of activin A(ACT A) and follistatin(FS)
      during mandibular lengthening and to elucidate the regulating pattern of during
      mandibular distraction osteogenesis. METHODS: Skeletally mature white New Zealand
      rabbits were established right mandibular distraction osteogenesis models and the
      mandibles were lengthened 7 days after osteomy. At the end of latency period and
      the end of distraction period, 10, 20, 30, 40 and 60 days after fixation, the
      regenerating tissue of animals' lengthened mandibles and that of the other side
      normal mandibles were harvested to extract RNA and to analyse ACT A, FS mRNA by
      RT-PCR. RESULTS: The expression of ACT A mRNA was not detectable in normal bone
      tissue and ACT A mRNA began to express at the end of latency period. The
      expression of ACT A mRNA increased gradually along with the beginning of
      distraction and reached the peak on the 10th and 20th days of distraction which
      was 5.04 and 4.98 times as much as that of the end of latency period,
      respectively. The trend of expression of FS mRNA during mandibular distraction
      osteogenesis was the same as expression of ACT A mRNA. CONCLUSION: ACT A/FS play
      an important role during rabbit mandibular distraction osteogenesis. To examine
      the mRNA expression of activin A(ACT A) and follistatin(FS) during mandibular
      lengthening and to elucidate the regulating pattern of during mandibular
      distraction osteogenesis.

PMID- 15460049
TI  - [Review and analysis of revision of total hip replacement].
AB  - OBJECTIVE: To evaluate the clinical value of the revision of total hip
      replacement(THR), to analyse the reason of the revisions, and to discuss the main
      difficulties and measures to manage it. METHODS: From June 1998 to January 2002,
      15 cases (15 hips) were revised on total hip replacement. The reasons for
      revision in the cases were as follows: failure of primary operative techenique,
      loosening and sinking of the components, displacement of the prosthesis, erosion
      of the acetabulum, as well as fracture of the femoral stem. The main difficulties
      of the revision were poor health condition of the patients; the remove of the
      prosthesis of the primary THR, especially the broken femoral stem and the
      cements; the loss of local bone. The measures to remove the broken femoral stem
      were described. RESULTS: All cases were followed up 2. 4 years on average: 2
      patients died from heart disease and cerebrovascular disease respectively, while
      the good results were achieved in the others. No infection, dislocation,
      loosening, and other complications occurred. The good effects were related with
      following factors: mild degree of illness; no severe bone defect; most of the
      first femoral head replacement. CONCLUSION: The revision of THR is a more
      difficult operation, so that the special instrument and equipment and operative
      experience are required.

PMID- 15460050
TI  - [Treatment of developmental dislocation of the hip with improved Pemberton
      method].
AB  - OBJECTIVE: To find a more perfect method of treating developmental dislocation of
      the hip(DDH). METHODS: From March 1994 to December 2002, on the basis of the
      ordinary operative method, Pemberton method was improved for 48 cases of DDH 49
      articulatio coxae which had superficial and small acetabula but big heads of
      femur. Osteotomy points were moved higher to enlarge area of bone flap turned
      over. A piece of full thickness ilium including periosteum was removed as a free
      bony graft. Capsula articularis growing thicker was made into 2 layers, of which
      the inner layer was used to tighten articularis and the outer layer was used to
      stabilize bone flap. RESULTS: All patients were followed up for 18 months to 5
      years, the function of articulatio coxae and degree of bony union, inclusion area
      to head of femur and ischemic necrosis of femoral head were observed through X
      ray. According to Zhou Yongde's criteria for the curative effect of congenital
      dislocation of the hip, there were 18 cases of 26-30 scores(3 hips), 27 cases of
      21-25 scores, 2 cases of 16-20 scores(3 hips), and 1 case under 15 scores, and
      the total superior rate was 93.8%. CONCLUSION: Improved Pemberton method can
      enlarge inclusion area to head of femur, avoid decreasing acetabular volume, and
      stabilize articulatio well, which made operative indication bigger than original
      Pemberton method.

PMID- 15460051
TI  - [Clinical application and relative examination of morselized bone].
AB  - OBJECTIVE: To review progress of clinical application of morselized bone and to
      investigate relative exploration on it. METHODS: The recent articles on
      morselized bone in the field of clinic and experimental research were extensively
      reviewed, and relative examination of morselized bone referring to method and
      mechanism were investigated carefully. RESULTS: Morselized bone worked well
      clinically, especially in revision of artificial total hip joint, and it was
      proved effective with lots of advantages. CONCLUSION: Morselized bone functions
      well clinically. Although its mechanism requires a further research, it still has
      a promising value in clinical application.

PMID- 15460052
TI  - [Experimental study of posterior pedicle screw placement on atlas].
AB  - OBJECTIVE: To assess the possibility of placing the posterior pedicle screw on
      atlas. METHODS: Twenty human cadaver specimens were used to insert pedicle screws
      in atlas, through the posterior arch or the pedicle of C1 into the lateral mass.
      The screw entry point was on the posterior surface of C1 posterior arch and at
      the intersection of the vertical line through the center of C2 inferior articular
      process and the horizontal line at least 3 mm below the superior rim of the C1
      lamina. The screw of 3.5 mm in diameter was placed in a direction of 10 degrees
      medial angle and 5 dgrees upward angle. After placement of C1 pedicle screw, the
      distance from C1 screw entry point to the medial-lateral midpoint of C1 pedicle,
      the maximum length of screw trajectory and the actual screw trajectory angles
      were measured. The direction of screw penetrating through the cortical of C1
      pedicle or lateral mass and the injuries to the vertebral artery and spinal cord
      were observed. RESULTS: Forty pedicle screws were placed on atlas, the mean
      distance from C1 screw entry point to the medial-lateral midpoint of C1 pedicle
      was (2.20 +/- 0.42)mm, the maximum length of screw trajectory averaged (30.51 +/-
      1.59)mm, and the actual screw trajectory angle measured (9.7 +/- 0.67)degrees in
      a medial direction and (4.6 +/- 0.59)degrees in a upward direction. Only 1 screw
      penetrated the upper cortical bone of the atlas pedicle because the upward angle
      was too large, and 8 screws were inserted so deep that the inferior cortical bone
      of the C1 lateral mass was penetrated. But no injuries to the vertebral artery
      and spinal cord were observed. CONCLUSION: C1 posterior pedicle screw fixation is
      quite accessible and safe, but the surgeons should pay attention to the angle and
      the depth of the screw placement.

PMID- 15460053
TI  - [Treatment of cervical radiculopathy by laminoplasty and foraminotomy].
AB  - OBJECTIVE: To evaluate the results of laminoplasty and foraminotomy in treatment
      of cervical radiculopathy. METHODS: Of 29 patients, there were 16 males and 13
      females, aged 38 to 72 years with an average of 59 years. The reasons of
      intervertebral foramen stenosis were prolapse of intervertebral disc, osteophyte
      formation of Luschka joint, spinal canal stenosis combined with thickness of
      flavum ligmentum and facet joint hypertrophy. The most frequently affected
      intervertebral foramen were C5.6 and C6.7. The most significant symptoms after
      impairment of nerve root were reduced sensation, muscle weakness and diminished
      reflexes. On the basis of laminoplasty, the foraminotomy was performed on the
      stenotic foramen, including grade I decompression on 13 occasions, degree II on
      21 occasions; and double level decompressions were performed on 5 patients.
      RESULTS: After operation, reduced sensation was recovered most significantly and
      quickly, and the recovery of muscle weakness followed, while the recovery of
      diminished reflexes was the slowest and worst. In the followed-up patients, the
      percentage of excellent and good results was 97%. CONCLUSION: In the cervical
      spondylotic patients who also have foraminar stenosis, performing laminoplasty
      with foraminotomy can get good results. If the indication are chosen properly, it
      can be used widely in clinic.

PMID- 15460054
TI  - [Application of Halo-vest in stable reconstruction of unstable upper cervical
      spine].
AB  - OBJECTIVE: To evaluate the clinical effect of Halo-vest in treatment of unstable
      upper cervical spine. METHODS: From March 1997 to October 2002, 16 cases of
      unstable upper cervical spines were treated and immobilized by Halo-vest, aged
      from 14 to 53 years. There were 3 cases of isolated Jefferson fractures, 4 cases
      of isolated Hangman fractures and 1 case of Anderson type I fracture. The 8 cases
      were immobilized for 3-4 months by Halo-vest. There were 3 cases of old odontoid
      fractures with dislocations treated by occipitocervical plate fixation and
      fusion, 1 case of C1 malignant tumor by posterior resection and internal
      fixation, 2 cases of C2 malignant tumor by anterior resection, fusion, and
      internal fixation; these cases were immobilized by Halo-vest during surgery.
      There were 1 case of C2.3 tuberculosis were treated by anterior debridement and
      fusion, and 1 case of gooseneck deformity by anterior decompression, fusion and
      screw fixation after resection of C2.7, the 2 cases were immobilized for 3 months
      by Halo-vest. Of 16 cases, there were 8 cases accompanied with spinal cord
      syndrome. RESULTS: Fifteen cases were followed up 6 months to 5 years. Anterior
      arch ununion and posterior arch osseous healing occurred in 1 case of Jefferson
      fracture. Other fractures and embedded bones became osseous fusion. One case of
      C2 malignant tumor recurred 8 months after operation. Spinal cord syndrome of all
      patients disappeared. CONCLUSION: Halo-vest immobilization is an effective method
      for conservative treatment and stable reconstruction of unstable upper cervical
      spine.

PMID- 15460055
TI  - [Experimental and clinical studies on selective sacral rhizotomy in treatment of
      spastic bladder after spinal cord injury].
AB  - OBJECTIVE: To observe the effect of selective sacral rhizotomy in treating
      spastic bladder after spinal cord injury and to explore the mechanism and the
      best surgical method of different sacral rhizotomies. METHODS: The spastic
      bladder models were established in 12 male dogs and were divided into 4 groups
      according to the different rhizotomies of the sacral nerve as the following:
      rhizotomy of the anterior root of S2 (group A), rhizotomy of the anterior root of
      S2 and half of the anterior root of S3 (group B), rhizotomy of the anterior roots
      of S2 and S3 (group C), and total rhizotomy of the nerve roots of S2-4 (group D).
      By urodynamic examination and electrophysiological observation, the changes of
      all functional data were recorded and compared between pre-rhizotomy and post
      rhizotomy to testify the best surgical method. In clinical trial, according to
      the results of the above experiments, rhizotomy of the anterior root of S2 or one
      of the half-anterior root of S3 were conducted on 32 patients with spastic
      bladder after spinal cord injury. The mean bladder capacity, the mean urine
      evacuation and the mean urethra pressure were (120 +/- 30), (100 +/- 30)ml and
      (120 +/- 20) cm H2O, respectively before rhizotomy. RESULTS: After rhizotomy, the
      bladder capacity in 4 groups amounted to (150 +/- 50), (180 +/- 50), (230 +/-
      50), and (400 +/- 50) ml, respectively; and the urine evacuation volume were (130
      +/- 30), (180 +/- 50), (100 +/- 50) and (50 +/- 30)ml, respectively. In the
      treated 32 patients, the mean bladder capacity were raised to 410 ml, and the
      mean urine evacuation volume were also increased to 350 ml. Incontinence of urine
      disappeared in all patients. After 22-month follow-up on 13 patients, no
      recurrence was observed. CONCLUSION: The effect of selective sacral rhizotomy in
      treating spastic cord injury is significant and worthy of further studies.

PMID- 15460056
TI  - [Blood flow changes of cauda equina in experimental lumbar spinal canal stenosis
      under dynamic burden].
AB  - OBJECTIVE: To study the changes of blood flow of the already-compressed cauda
      equina under dynamic burden, high frequency stimulation (HFS) and increased
      additional compression, and to clarify the mechanism of neurogenic intermittent
      claudication. METHODS: Thirty SD rats were divided into 5 groups, 6 in each. All
      groups were operated with laminectomy of the fifth lumbar verfebra. One hour
      after the measurement of blood flow, in 4 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 to the subjects of the experimental group 1. Only
      HFS was introduced to the subjects of the experimental group 2 for 6 minutes.
      Both HFS and increased additional compression were introduced to the subjects of
      the experimental group 3 for 6 minutes. While only increased additional
      compression was introduced to the subjects of the experimental group 4 for 6
      minutes. The subjects of control group only underwent laminectomy of the fifth
      lumbar vertebra and HFS 6 minutes. The blood flow of cauda equina was measured
      with laser Doppler flowmeter. RESULTS: In the first 2 hours, there was no
      significant change of cauda equina blood flow in the control group. During the
      time of HFS, the blood flow increased significantly to 186.4% +/- 31.5% of
      initial value (P < 0.05). In the experimental group 1, there was no blood flow
      change during the period of dynamic burden(110.4% +/- 7.5%, P > 0.05). After
      introduction of dynamic burden, there was no blood flow changes in the
      experimental group 2 (111.6% +/- 17.6%, P > 0.05). The blood flow in the
      experimental group 3 decreased to 65.3% +/- 10.7% of initial value (P < 0.05);
      and the blood flow in the experimental group 4 decreased to 60.1% +/- 9.2% of
      initial value (P < 0.01). There was no significant difference between the
      experimental groups 3 and 4 (P > 0.05). CONCLUSION: The results above show that
      during the period of increased impulse transmission, double level compression of
      cauda equina may limit the increase of blood flow, which may cause relative
      ischemia. If there is increased additional compression along with increased
      impulse transmission, the blood flow will decrease significantly, which will
      cause absolute ischemia.

PMID- 15460057
TI  - [Expression of nerve growth factor mRNA and nerve regeneration after
      discontinuous injection of phorbol-12-myristate-13-acetate into silicone
      chamber].
AB  - OBJECTIVE: To study the mRNA expressions of protein kinase C(PKC) and nerve
      growth factor (NGF) in rat sciatic nerve and the number of axons after phorbol-12
      myristate-13-acetate (PMA) was injected into silicone chamber. METHODS: Forty-two
      SD adult rats were divided into six groups depending on the time of injury (1
      day, 3 days, 1 week, 2 weeks, 3 weeks and 4 weeks). A 0.5 cm nerve was cut in
      double rat sciatic nerves and "T" type silicone chamber was sutured. PMA at the
      concentration of 1 x 10(-9) mol/L was injected discontinuously into the right
      side of T type silicone chamber (PMA group) and saline was injected into the left
      side (control group). Nucleic acid in situ hybridization histochemistry technique
      and the computer imagine analysis were employed to detect dynamic changes of PKC
      mRNA and NGF mRNA in rat sciatic nerves. The number of axons was measured.
      RESULTS: The expressions of PKC mRNA and NGF mRNA increased after injury, and the
      expressions of PKC mRNA and NGF mRNA reached the peak 2 weeks and 3 weeks after
      injury respectively in control group. The expressions of PKC mRNA and NGF mRNA in
      PMA group were significantly increased than those in control group 2,3 and 4
      weeks after injury (P < 0.01). The number of axons in PMA group significantly
      increased than that in control group (P < 0.01). CONCLUSION: PKC involved in the
      expression of NGF mRNA and nerve regeneration after injury. During the
      regenerated course, PMA can promote the expression of NGF mRNA and the number of
      axons after injury.

PMID- 15460058
TI  - [Recovery and evoked potential of nerve root under variable chronic injury].
AB  - OBJECTIVE: To study the recovery and mechanism of nerve root under variable
      chronic injury and to determine the alerting index of the evoked potential of the
      irreversible injury to the nerve root, so as to offer the evidence for selecting
      treatment methods, judging prognosis and grasping treatment juncture. METHODS:
      Autogenous cancellous bones were planted into the right C7-8 and C8-T1
      intervertebral foramens in 30 cats with weight 3-5 kg to make chronic injury
      models. The left side was for auto-contrast. By 24 weeks' observation and dynamic
      supervisory of evoked potential, the injury degrees were ascertained and
      classified into I to V degree groups. Then the operation of decompression was
      performed on every group. During the following 32 weeks, the evoked potential
      survey and pathological tissue examination were made every week to observe the
      function recovery of the injured roots. RESULTS: The tissue form and function of
      the nerve roots with I and II degree injuries recovered well within 2 to 6 weeks.
      Those with II degree injury began to recover in the 4th week, and gradually
      recovered to normal 12 weeks later. In the group of IV degree injury, the
      recovery was slow. They could recover completely in 3 of 6 cats, partly in 2 and
      hardly recovered in 1. The function and tissue form of nerve roots with V degree
      injury could hardly recovered. CONCLUSION: In the case that the compression has
      been removed before the nerve roots suffer II degree injury. The tissue form and
      function of the nerve roots will recovered satisfactorily, whereas they may
      suffer irreversibly injury by IV degree injury, and even can hardly recover by V
      degree injury. During the supervisory process of the recovery of the injured
      nerve roots, sensitive evoked potential is a sensitive sign of early recovery and
      motion evoked potential is a reliable sign of recovery extent.

PMID- 15460059
TI  - [Application of the dorsoulnar arterial retrograde flap of the thumb to repair of
      soft tissue defect at the distal thumb].
AB  - OBJECTIVE: To introduce the surgical procedure and indication of the dorsoulnar
      arterial retrograde flap of the thumb in repair of soft tissue defect. METHODS:
      From March 2000 to March 2001, 12 cases of soft tissue defect with exposed bone
      at the distal thumb were involved. Ten flaps were pedicled distally at the
      proximal rotation point, 2.5 cm proximal to the cuticule. Two flaps were pedicled
      distally at the distal rotation point, 1.0 cm proximal to the cuticule. The flaps
      harvested in this study were 1.1 cm x 1.3 cm to 1.8 cm x 2.5 cm. RESULTS: All the
      flaps survived. After an follow-up of 2 to 14 months postoperatively, the
      appearance of the thumbs were satisfactory, except those of 2 thumbs repaired by
      the flaps transferred at the distal rotation point, which were bulkiness because
      of the uncovered pedicle. In 6 cases, the defect of finger pulp was repaired, and
      the 2-point discrimination was measured 8-10 mm. The same range of motion of the
      thumb IP joint were observed in both sides in all cases. CONCLUSION: The optimal
      indication of the procedure is soft tissue defect at the distal thumb.

PMID- 15460060
TI  - [Development of selective acellular porcine skin and its preliminary clinical
      application on burn wounds].
AB  - OBJECTIVE: To develop a new kind of skin substitute, selective acellular porcine
      skin, to cover excised wounds in treatment of extensive deep burns on the basis
      of controlled de-cell technique. METHODS: Partial thickness porcine skin was
      treated with 0.25% trypsin for 2 hours at 37 degrees C after crosslinked with
      glutaraldehyde, and then it was glued to a container with the edge embedded with
      glue. The skin was shaken in 0.5% SDS for 24 hours, and then washed before use.
      The selective acellular skin was used with micro-autografts on the dermal side to
      cover 2 surgically excised burn wounds in a patient. The recoveries of function
      and appearance were observed. RESULTS: Morphological observation showed that the
      treated porcine skin had an intact epithelial layer and an acellular dermis.
      After being used to cover burn wounds, its acellular dermis could serve as host
      dermal matrix, and its devitalized epithelial layer could prevent the dermis from
      drying. The devitalized epithelium was finally replaced by host epithelial cells,
      and the healed wounds could achieve good cosmetic and functional results.
      CONCLUSION: Selective acellular porcine skin can be used as promising skin
      substitute to cover excised wounds.

PMID- 15460061
TI  - [Possibility of using cartilage cultured in centrifuge tube as a substitute for
      meniscus].
AB  - OBJECTIVE: To compare biological characteristics between articular chondrocyte
      and meniscal fibrochondrocyte cultured in vitro and to investigate the
      possibility of using cultured cartilage as a substitute for meniscus. METHODS:
      Chondrocytes isolated from articular cartilage and meniscus of rabbits aged 3
      weeks were respectively passaged in monolayer and cultured in centrifuge tube.
      Cartilages cultured in centrifuge tube and meniscus of rabbit aged 6 weeks were
      detected by histological examination and transmission electron microscopy. Growth
      curves of articular chondrocytes and meniscal fibrochondrocytes were compared;
      meanwhile, cell cycles of articular chondrocytes and meniscal fibrochondrocytes
      in passage 2 and 4 were separately measured by flow cytometry. RESULTS: Articular
      chondrocytes in passage 4 were dedifferentiated. Articular chondrocytes formed
      cartilage 2 weeks after cultivation in centrifuge tube, but meniscal
      fibrochondrocytes could not generate cartilage. The differences in ultrastructure
      and histology obviously existed between cultured cartilage and meniscus;
      moreover, apoptosis of chondrocytes appeared in cultured cartilage. Proportion of
      subdiploid cells in articular chondrocytes passage 2 and 4 was markedly higher
      than that in passage 2 and 4 fibrochondrocytes (P < 0.05). CONCLUSION: Meniscal
      fibrochondrocytes can not form cartilage after cultivation in centrifuge tube,
      while cartilage cultured in centrifuge tube from articular chondrocytes can not
      be used as graft material for meniscus. Articular cartilage is markedly different
      from meniscus.

PMID- 15460062
TI  - [Effect of human acellular amnion membrane on tendon adhesion in rat].
AB  - OBJECTIVE: To investigate the effects of human acellular amnion membrane on SD
      rat tendon adhesion and to obtain the experimental data for clinical application
      in preventing postoperative tendon adhesion. METHODS: The tendons of 28 adult SD
      rats hindlimb were cut and sutured. The tendons of left hindlimb were
      encapsulated by human accellular amnion membrane as the experimental group and
      the ones of the other side were not encapsulated as control group. The rats were
      killed 1, 2, 4, 6, 8 and 12 weeks after operation. The results were evaluated
      grossly and histologically. RESULTS: There were no differences in healing of
      injury tendon and inflammatory response between the two groups. The anatomical
      and histological results showed the experimental group had less adhesion than the
      control group (P < 0.05). CONCLUSION: Human acellular amnion membrane can prevent
      adhesion of tendon without affecting tendon healing and is an optimal biological
      material to prevent tendon adhesion.

PMID- 15460063
TI  - [Construction and expression of basic fibroblast growth factor mammalian
      expression vector].
AB  - OBJECTIVE: To construct a mammalian expression vector of basic fibroblast growth
      factor (bFGF) and to investigate the expression of bFGF in vitro and in vivo.
      METHODS: A mammalian expression vector pcDNA3. 1/ myc-His(-)C-bFGF was
      constructed with gene cloning technique. The mammalian expression system was
      prepared and purified. The expression of bFGF cDNA in cultured transfected cells
      was examined by RT-PCR and cell immunohistochemistry. The recombinant plasmids,
      pcDNA3. 1/myc-His(-)C-bFGF and pCD2-VEGF121, were transferred into rabbit
      cervical muscle by direct injection of plasmid following electric pulses in vivo.
      The transferred gene expression and the biological effect were measured by use of
      histochemistry and immunohistochemistry analysis. RESULTS: The eukaryon
      expression system pcDNA3. 1/myc-His (-)C-bFGF could express the target protein
      bFGF in vitro. The recombinant plasmids, pcDNA3. 1/myc-His(-)C-bFGF and pCD2
      VEGF121 were transferred into muscles flap in vivo successfully. The active
      proteins bFGF and VEGF121 were expressed at high levels. Blood vessels increased
      significantly in the muscles, and blood circulation was improved by local
      angiogenesis. CONCLUSION: The eukaryon expression vector of bFGF is constructed
      and can be expressed successfully in vitro and in vivo. That is a primary
      preparation for the research on tissue transplantation and tissue engineering
      with bFGF gene therapy.

PMID- 15460064
TI  - Biodiversity of human faecal bacteria isolated from phytic acid enriched
      chemostat fermenters.
AB  - BACKGROUND: Myo-inositol hexaphosphate (IP6) or phytic acid is found mostly in
      cereals and legumes and is thought to possess anti-carcinogenic properties. AIM:
      To isolate and identify faecal bacteria capable of phytic acid metabolism and to
      assess the effectiveness of prebiotics (dietary oligosaccharides, metabolised by
      selective colonic bacteria) in preserving the integrity of phytic acid. METHODS:
      Faecal samples from three volunteers were used in continuous culture experiments
      under varying conditions of pH, substrate concentration and dilution rates,
      seventy three different isolates cultured at steady state were then screened for
      phytic acid metabolism and identified through partial sequencing of their 16S
      rRNA genes (16S ribosomal ribonucleic acid). Utilisation of phytic acid was also
      assessed in a continuous culture system enriched with prebiotic
      fructooligosaccharides (FOS). RESULTS: Bacteroides spp., Clostridium spp. and
      facultatively anaerobic bacteria generally appeared to maintain viable counts in
      the presence of phytic acid. Bifidobacterium spp. and Lactobacillus spp. appeared
      less able to maintain viable counts in the presence of phytic acid. These results
      were confirmed by an increase in viable counts of Bacteroides spp., Clostridium
      spp. and a decrease in viable counts of Bifidobacterium spp. and Lactobacillus
      spp. once phytic acid was introduced to a FOS enriched continuous culture.
      CONCLUSIONS: The phytate metabolising biodiversity from the human large intestine
      does not appear to encompass major bacterial genera associated with beneficial or
      benign health effects (e.g. Lactobacillus spp. and Bifidobacterium spp).

PMID- 15460065
TI  - Molecular microbial ecology of the gastrointestinal tract: from phylogeny to
      function.
AB  - During the past decade it became evident that anaerobic cultivation-based
      approaches provides an incomplete picture of the microbial diversity in the GI
      tract, since at present only a minority of microbes can be obtained in culture.
      The application of molecular, mainly 16S ribosomal RNA (rRNA)-based approaches
      enables researchers to bypass the cultivation step and has proven its usefulness
      in studying the microbial composition in a variety of ecosystems, including the
      gastrointestinal (GI) tract. This critical review summarizes the impact of these
      culture-independent approaches on our knowledge of the ecology of the GI tract
      and provides directions for future studies which should emphasize function of
      specific strains, species and groups of microbes.

PMID- 15460066
TI  - Intestinal population dynamics of UTI-causing Escherichia coli within
      heterosexual couples.
AB  - From October 1999 to July 2001, a prospective cohort study was conducted to
      assess the intestinal Escherichia coli population dynamics of 23 sexually active
      couples. We tested the hypothesis that intestinal persistence and predominance of
      specific E. coli strains, co-colonization of sex partners with the same E. coli
      strain, and the intestinal diversity of fecal E. coli, contribute to recurrent
      urinary tract infection (UTI). E. coli isolates causing UTI, asymptomatic
      bacteriuria (ABU), or intestinal co-colonization were evaluated by ERIC2 PCR and
      compared with strains recovered exclusively from stool samples with respect to
      intestinal persistence, predominance, and diversity. Contrary to our hypothesis,
      UTI-causing strains exhibited similar levels of intestinal persistence and
      predominance as did fecal strains, and UTI episodes were not associated with
      shifts in fecal E. coli diversity. In contrast, intestinal co-colonization
      strains exhibited greater persistence and predominance than did fecal strains and
      were more likely to cause ABU, and co-colonization episodes were associated with
      significantly increased fecal E. coli diversity. Nonetheless, intestinal co
      colonization strains were not associated with UTI. These findings suggest that E.
      coli strains involved in co-colonization may be more important contributors to
      intestinal E. coli dynamics than to UTI pathogenesis.

PMID- 15460067
TI  - Comparative composition of bacteria in the human intestinal microflora during
      remission and active ulcerative colitis.
AB  - Ulcerative colitis is a severe, relapsing and remitting disease of the human
      large intestine characterised by inflammation of the mucosa and submucosa. The
      main site of disease is the sigmoid/rectal region of the large bowel but the
      aetiology remains unknown. There is considerable evidence to indicate that the
      components of the resident colonic microflora can play an important role in
      initiation of the disease. The present study was aimed at characterising the
      faecal microflora of ulcerative colitis patients in remission and active phases
      to determine profile differences. Faecal samples were obtained from 12 patients,
      6 with active colitis and 6 in remission. The samples were analysed for
      populations of lactobacilli, bifidobacteria, clostridia, bacteroides, sulphate
      reducing bacteria (SRB) and total bacteria using culture independent fluorescence
      in situ hybridisation (FISH). Lactobacillus-specific denaturing gradient gel
      electrophoresis (DGGE) was then performed to compare the species present. Numbers
      of lactobacilli were significantly lower (p<0.05) during the active phase of the
      disease but the other populations tested did not differ. DGGE analysis revealed
      that Lactobacillus salivarus, Lactobacillus manihotivorans and Pediococcus
      acidilactici were present in remission, but not during active inflammation. These
      results imply that a reduction in intestinal Lactobacillus species may be
      important in the initiation of ulcerative colitis.

PMID- 15460068
TI  - Relationship between scintigraphic and radiographic evaluations of spinous
      processes in the thoracolumbar spine in riding horses without clinical signs of
      back problems.
AB  - REASONS FOR PERFORMING STUDY: Radiography and scintigraphy are used to aid
      diagnosis of the cause of back pain, but a large variation in appearance and
      radiopharmaceutical uptake in fully functioning horses make diagnosis difficult.
      OBJECTIVES: To describe the range of and compare scintigraphic and radiographic
      findings in the spinous processes of horses without clinical signs of back
      problems. METHODS: Thirty-three apparently normal riding horses underwent
      scintigraphic and radiographic examinations of the spinous processes in the
      thoracolumbar spine. Scintigraphic images were evaluated in a continuous blue,
      green and red colour scale, and the level of radiopharmaceutical uptake in the
      spinous processes from T10-L2 was graded into none, mild, moderate or severe
      increased radiopharmaceutical uptake. Structural changes along the borders of the
      spinous processes and the width of the interspinous spaces from T10-L2 were
      recorded. RESULTS: Only 7 horses had no scintigraphic or radiographic findings.
      Nine horses had no increased radiopharmaceutical uptake, 17 had no sclerosis, 21
      had no radiolucencies and 11 had normal spacing of the spinous processes (>4 mm
      wide). The majority of findings in 26 horses were located from T13-18 and were
      mild. CONCLUSIONS: The findings of a wide spectrum of scintigraphic and
      radiographic changes leads to the conclusion that changes within this range found
      in affected horses cannot be interpreted as clinically significant. POTENTIAL
      RELEVANCE: To determine whether scintigraphy and/or radiography can be used to
      separate horses with back pain from horses without clinical signs, the results
      from this study should be compared to the scintigraphic and radiographic findings
      in horses with clinical signs.

PMID- 15460069
TI  - Clinical anatomy of the equine sphenopalatine sinus.
AB  - REASONS FOR PERFORMING STUDY: Disorders of the equine sphenopalatine sinus,
      including empyema and neoplasia, have been reported to cause damage to cranial
      nerves II and V. However, the clinical anatomy of these sinuses is not well
      described in horses. OBJECTIVE: To examine the anatomy of the sphenopalatine
      sinuses in a range of equidae and, in particular, to examine the relationship of
      these sinuses to adjacent major nerves and vessels. METHODS: The anatomy of the
      sphenoidal and palatine paranasal sinuses was examined in 16 equidae, primarily
      using transverse skull sections. Relevant structures were documented and
      photographed. RESULTS: There was much variation between individual horses in
      sphenopalatine sinus anatomy. The sphenoidal sinuses were small in young horses
      and appeared to become larger and more complex with age. Variation was present in
      the extent that the sphenopalatine sinus extended into the basisphenoid bone. The
      septum dividing left and right sphenoidal sinuses was frequently not midline, but
      was intact in all cases. The sphenoidal and palatine sinuses communicated in most
      horses. In such cases, what could accurately be termed the (combined)
      sphenopalatine sinuses usually drained directly into the caudal maxillary
      sinuses. Additionally, in 5 out of 16 cases, some compartments of the sphenoidal
      sinus also drained into the ethmoidal sinus. The dorsal and lateral walls of the
      sphenoidal sinus were very thin and directly adjacent to cranial nerves II, III,
      IV, V and VI and major blood vessels. CONCLUSIONS: The equine sphenoidal and
      palatine sinuses are very variable in their anatomy, but are always in close
      proximity to multiple cranial nerves and major blood vessels. POTENTIAL
      RELEVANCE: Many cranial nerves and blood vessels could be damaged with disorders
      involving the sphenopalatine sinus, potentially causing major and variable
      neurological syndromes, haemorrhage and extension of sepsis.

PMID- 15460070
TI  - Interstitial cells of Cajal (ICC) in equine colic: an immunohistochemical study
      of horses with obstructive disorders of the small and large intestines.
AB  - REASONS FOR PERFORMING STUDY: The gastrointestinal pacemaker cells, the
      interstitial cells of Cajal (ICC), have been implicated in several human
      gastrointestinal dysmotility syndromes. Recently, the involvement of these cells
      in equine gastrointestinal diseases has been investigated in cases of equine
      grass sickness where a significant reduction in ICC density was observed.
      OBJECTIVE: To investigate ICC density in equine obstructive gastrointestinal
      disorders using immunohistochemical labelling methods. METHODS: Intestinal
      samples were analysed from 44 horses undergoing exploratory surgery for colic and
      from 11 control animals subjected to euthanasia for conditions not related to the
      gastrointestinal tract. Immunohistochemical labelling of ICC was carried out
      using an anti-c-Kit antibody. Two independent observers assessed ICC density
      using a semiquantitative grading system. RESULTS: There was a significant
      reduction in ICC density in horses with large colon disorders compared to the
      controls (P<0.01). Horses with strangulating lesions of the small intestine
      showed no difference when compared to the controls. CONCLUSIONS: There was a
      reduction in ICC density in horses with large intestinal disorders. POTENTIAL
      RELEVANCE: The reduction in ICC density may be associated with the clinical
      findings as well as recurrent colic episodes observed in a number of these cases.
      This immunohistochemical study provides a basis for future functional
      electrophysiological investigations to determine the precise effect of ICC
      reduction on equine intestinal motility.

PMID- 15460071
TI  - Hyaluronan in horses: physiological production rate, plasma and synovial fluid
      concentrations in control conditions and following sodium hyaluronate
      administration.
AB  - REASONS FOR PERFORMING STUDY: Hyaluronic acid (HA) is an endogenous
      glycosaminoglycan used in the treatment of joint diseases, but medication control
      is required by horseracing authorities. Therefore, a medication control policy
      needs to be established. OBJECTIVES: To establish physiological plasma HA
      concentrations in post race horses, determine the HA endogenous production rate
      and document the disposition of HA after i.v. and intra-articular hyaluronic acid
      administration at recommended therapeutic doses. METHODS: Hyaluronan
      concentrations in plasma were determined using an ELISA specific test;
      concentrations in synovial fluid were determined using a radiometric binding
      assay. RESULTS: The overall mean plasma HA concentration in 120 post competition
      horses was 89 ng/ml. In a group of 6 experimental horses, synovial fluid control
      concentration was 328+/-112 microg/ml. After i.v. sodium hyaluronate
      administration (37.8 mg in toto), the terminal half-life was very short (43+/-29
      mins) and after a delay of 3 h, the plasma concentration returned to control
      values. The endogenous HA production rate was 33-164 mg in toto per day, i.e. 1-4
      times the recommended i.v. daily dose. Twenty-four hours after intra-articular
      administration, HA concentration was not significantly different from control
      values (328+/-112 microg/ml). CONCLUSIONS AND POTENTIAL RELEVANCE: Due to the
      rapid disappearance of HA from plasma after i.v. administration and from the
      joint after intra-articular administration, long-term detection needs a more
      appropriate approach to be developed.

PMID- 15460072
TI  - The effects of a single acupuncture treatment in horses with severe recurrent
      airway obstruction.
AB  - REASONS FOR PERFORMING STUDY: Acupuncture may be recommended for horses with
      'heaves' because it is being increasingly applied to treat human asthma.
      Therefore, its efficacy was investigated in horses with this asthma-like disease.
      OBJECTIVE: To evaluate the efficacy of a single acupuncture treatment for the
      relief of airway obstruction in heaves-affected horses. METHODS: The efficacy of
      a single acupuncture treatment was tested in 10 heaves-affected horses, and the
      effect of removal from the dusty stall environment in 5 heaves-affected horses.
      Before treatment, horses were stabled to induce airway obstruction and, apart
      from trips to the laboratory for pulmonary function measurements, they remained
      stabled for the duration of each treatment. The severity of airway obstruction
      was quantified by measurement of lung function before treatment (baseline), and
      at 20, 60, 120 and 240 mins and 24 h after the following treatments administered
      in random order: halter restraint and patting, a single acupuncture treatment by
      an experienced acupuncturist, and a single acupuncture treatment using
      predetermined points (recipe) by a veterinarian with no acupuncture training. In
      a second study, horses were untreated and remained either in their stall or in a
      paddock for all measurements of lung function, after baseline readings were made.
      RESULTS: In the first study, after all treatments, there was a temporal
      improvement in maximal change in pleural pressure, pulmonary resistance, dynamic
      compliance, respiratory rate, and tidal volume that lasted less than 24 h. There
      was no specific effect of acupuncture treatment. In the second study, removal
      from the dusty environment did not produce an improvement in lung function in the
      first 6 h. We conclude that most of the improvements in lung function observed in
      the study were due to handling. CONCLUSIONS: Assessed objectively, a single
      acupuncture treatment during an attack of heaves causes no more improvement in
      lung function than does handling the horse. POTENTIAL RELEVANCE: Acupuncture
      should not replace conventional medical treatments for heaves.

PMID- 15460073
TI  - Kinematic evaluation of the back in fully functioning riding horses.
AB  - REASONS FOR PERFORMING STUDY: Clinical history and examination are important
      features in diagnosis of equine back dysfunction. However, interpretation is
      subjective and therefore may vary substantially. OBJECTIVES: To establish a
      clinical tool to objectively evaluate the function of the equine back, in the
      form of a database on the kinematics of the back at the walk and trot in fully
      functioning riding horses. METHODS: Thirty-three fully functioning riding horses
      walked and trotted on a treadmill. Morphometrics and kinematics were tested for
      correlations to age, height, weight and stride length, and differences between
      gender (geldings and mares) and use (dressage and showjumping). RESULTS: A
      database for range of movement and symmetry of movement for extension and
      flexion, lateral bending, lateral excursion and axial rotation was presented.
      Symmetry values were very high for all variables. Significant differences were
      observed in use and gender. Age was negatively correlated to extension and
      flexion of the thoracolumbar junction. CONCLUSIONS: Interrelationships between
      use, gender and age to conformation and movement were established. POTENTIAL
      RELEVANCE: The database provides a basis for objective reference for diagnosis,
      therapy and rehabilitation of clinical cases of back dysfunction.

PMID- 15460074
TI  - Onset of puberty in pasture-raised Thoroughbreds born in southern hemisphere
      spring and autumn.
AB  - REASONS FOR PERFORMING STUDY: There is little information on age, weight and time
      of year of puberty in Thoroughbred horses, and the interpretation of such data is
      difficult due to the wide variety of descriptions of the onset of puberty.
      OBJECTIVES: To examine the age, bodyweight and date of onset of puberty in
      Thoroughbreds born in spring and autumn. METHODS: Bodyweight data and blood
      samples were collected in 59 pasture-raised Thoroughbred horses. Five autumn-born
      and 18 spring-born colts and 3 autumn-born and 33 spring-born fillies were
      examined from birth to age 13 and 17 months. A testosterone concentration >2 s.d.
      above the baseline concentration was indicative of onset of puberty in colts; and
      progesterone concentration >2 ng/ml and at least 3 times greater than the
      previous progesterone concentration was indicative of a first ovulation in
      fillies. RESULTS: Spring-born fillies and colts were older and heavier than
      autumn-born fillies and colts at puberty. The age at onset of puberty in spring-
      and autumn-born foals was 291-408 days and 212-270 days, respectively. The weight
      at puberty in spring-born foals was 302-409 kg, and in autumn-born foals was 277
      344 kg. However, the mean date at onset of puberty was not significantly
      different between spring- and autumn-born horses, with puberty occurring in
      October (New Zealand spring). CONCLUSIONS AND POTENTIAL RELEVANCE: Seasonal
      changes in photoperiod affect the timing of onset of puberty, provided a minimum
      threshold bodyweight has been reached. Spring-born horses reached this threshold
      weight during the winter months and remained reproductively inactive until after
      the stimulus of increasing day-length occurred. The autumn-born horses reached
      the threshold weight to support puberty at the same time as stimulatory
      photoperiod and, therefore, reached puberty significantly younger and lighter
      than the spring-born horses.

PMID- 15460075
TI  - Differences in the topographical distribution of articular cartilage degeneration
      between equine metacarpo- and metatarsophalangeal joints.
AB  - REASONS FOR PERFORMING STUDY: The equine metacarpophalangeal (MCP) and
      metatarsophalangeal (MTP) joints, although having virtually the same geometrical
      appearance, differ in the prevalence of joint pathologies, such as osteochondral
      fragmentation, and in biomechanical behaviour. The recently developed cartilage
      degeneration index (CDI) technique offers a possibility to assess quantitatively
      differences in cartilage degeneration between these joints and to compare these
      with known differences in biomechanics and clinical observations. OBJECTIVES: To
      compare the topographical distribution of articular cartilage degeneration across
      the proximal articular surface of the proximal phalanx (P1) in the equine fore-
      and hindlimb. METHODS: In 24 distal hindlimbs from 24 horses, articular cartilage
      degeneration of the proximal articular surface of P1 was quantified using the
      CDI. Overall CDI value (CDI(P1)) and CDI values of 6 areas of interest were
      determined: the medial dorsal surface (mds), lateral dorsal surface (lds), medial
      central fovea (mcf), lateral central fovea (lcf), medial plantar surface (mps)
      and lateral plantar surface (lps). The joints were divided into 4 equally sized
      groups of increasing CDI(P1) values. From an existing CDI database of MCP joints,
      24 joints were selected with matching CDI(P1) values to the MTP joints and CDI
      values for the same areas of interest were determined. RESULTS: In both the MCP
      and MTP joints, highest CDI values were determined at the dorsal articular
      surfaces. Values were not significantly different between fore- and hindlimbs. In
      contrast to the MCP joint, CDI values at the plantar joint margin were
      significantly higher compared to CDI values in the central sites in the MTP
      joint. CDI values for the plantar surfaces of P1 were significantly higher than
      those for the palmar surfaces in the forelimb in joints with advanced stages of
      OA; and values for the central regions of P1 were significantly lower in the
      hindlimb compared with the forelimb in joints with severe OA. CONCLUSIONS: In
      both fore- and hindlimbs, initial cartilage degeneration started at the dorsal
      articular margin of P1. There was a major difference in the spread of cartilage
      degeneration; in the forelimb both the central and palmar parts are about equally
      involved, whereas in the hindlimb the plantar parts were significantly more and
      the central parts significantly less involved. These differences can be linked to
      differences in biomechanical loading reported elsewhere. POTENTIAL RELEVANCE:
      This study supports the hypothesis that differences in biokinematics between fore
      and hindlimbs are associated with differences in the development of cartilage
      degeneration and other joint pathologies such as osteochondral fragmentation in
      the MCP and MTP joints. This information is indispensable for a better
      understanding of the dynamic nature and progression of these joint disorders and
      may be of help when monitoring the effects of therapeutic interventions and
      preventative measures.

PMID- 15460076
TI  - Horse-level risk factors for fatal distal limb fracture in racing Thoroughbreds
      in the UK.
AB  - REASONS FOR PERFORMING STUDY: Fractures below the level of the radius or tibia
      (distal limb fractures) are the most common cause of equine fatality on UK
      racecourses; however, little is known about their epidemiology or aetiology.
      Identification of risk factors could enable intervention strategies to be
      designed to reduce the number of fatalities. OBJECTIVES: To identify horse-level
      risk factors for fatal distal limb fracture in Thoroughbreds on UK racecourses.
      METHODS: A case-control study design was used. Fractures in case horses were
      confirmed by post mortem examination and 3 matched uninjured controls were
      selected from the race in which the case horse was running. One hundred and nine
      cases were included and information was collected about previous racing history,
      horse characteristics and training schedules. Conditional logistic regression was
      used to identify the relationship between a number of independent variables and
      the likelihood of fracture. RESULTS: Horses doing no gallop work during training
      and those in their first year of racing were at significantly increased risk of
      fracture on the racecourse. Case horses were also more likely to have trained on
      a sand gallop, i.e. a gallop described by trainers as being primarily composed of
      sand. CONCLUSIONS: Modifications to training schedules, specifically within the
      first year of racing, may have a large impact on the risk of fatal distal limb
      fracture on the racecourse. Horses should do some gallop work in training and our
      results suggest that the minimum distance galloped should be between 805-2012 m
      (4-10 furlongs)/week. POTENTIAL RELEVANCE: The information from this study can be
      used to alter training schedules in an attempt to reduce the incidence of fatal
      distal limb fracture in Thoroughbred racehorses. Training should include some
      gallop work, and further studies, recording the exact level of work, will help to
      identify an optimum range of training speeds and distances which will reduce the
      liklihood of catastrophic fracture on the racecourse.

PMID- 15460077
TI  - Race- and course-level risk factors for fatal distal limb fracture in racing
      Thoroughbreds.
AB  - REASONS FOR PERFORMING STUDY: Considerable variation in the rates of equine
      fatality at different racecourses draws attention to probable risk factors at the
      level of course or race that might be partly responsible. Distal limb fractures
      are the most common cause of equine fatality on UK racecourses and identification
      of risk factors for such injuries and subsequent implementation of intervention
      strategies could significantly reduce the total number of racecourse fatalities.
      OBJECTIVES: To identify race- and course-level risk factors for fatal distal limb
      fracture in Thoroughbreds on UK racecourses. METHODS: A case-control study design
      was used. Case races were defined as those in which one or more horses sustained
      fatal fracture of the distal limb. Controls were selected in 2 different ways.
      Firstly, 3 races in which no fracture occurred were selected from all races of
      the same type held within 5 days of the case race (Analysis 1). Secondly, 3
      control races were selected for each case race from all races of the same type
      held in the same year (Analysis 2). One hundred and nine cases were included in
      the study. Information about the race and the racecourses was collected from
      Computer Raceform. Conditional logistic regression was used to identify the
      relationship between a number of independent variables and the likelihood of
      fracture in a race. RESULTS: Longer races with a larger number of runners were
      more likely to contain a fracture. Firmer going and fewer days since the last
      race on the same course were associated with an increased risk of fracture. The
      going at the course at the previous race meeting was also associated with the
      likelihood of fracture. CONCLUSIONS: Modifications to the going on the day of a
      race and greater emphasis on ground maintenance between race meetings may have an
      impact on the risk of fatal distal limb fracture during racing. POTENTIAL
      RELEVANCE: Modification of risk factors such as the going and number of days
      since the last race meeting could reduce the number of equine fatalities on UK
      racecourses. The condition of the racecourse may be an important risk factor and
      future research should focus on the identification of course maintenance
      techniques that produce the safest possible racing surfaces.

PMID- 15460078
TI  - Tenoscopic surgery for treatment of lacerations of the digital flexor tendon
      sheath.
AB  - REASONS FOR PERFORMING STUDY: Lacerations to the digital flexor tendon sheath
      (DFTS) are a common injury in the horse, but little information is available in
      the literature regarding prognostic indicators. OBJECTIVE: To ascertain whether
      laceration of the DFTS carried a better prognosis if treated by tenoscopic
      lavage, debridement and repair within 36 h of the original injury. METHODS: A
      retrospective analysis of 39 horses treated surgically for lacerations to the
      DFTS was performed over a 3 year period. The injury-to-surgery interval was
      recorded as <36 or >36 h. The structures damaged by the injury were also
      recorded, as well as age, sex, use and outcome. RESULTS: Sixteen horses had
      laceration and contamination of the DFTS alone, of which 15 (94%) returned to
      their original or intended use. Sixteen horses had lacerations involving the
      superficial digital flexor tendon, of which 12 (75%) made a full recovery. Six
      horses had lacerations to both superficial and deep digital flexor tendons, 5
      were subjected to euthanasia intraoperatively and one is paddock sound. Treatment
      within 36 h of initial laceration carried a significantly better prognosis for
      return to intended athletic use (25 of 28 horses allowed to recover from
      anaesthesia) than treatment after 36 h (2 of 5 P = 0.03; Fisher's Exact Test).
      CONCLUSIONS: If sepsis is treated early using tenoscopic visualisation, lavage
      and repositol antibiotics, the limiting factor in return to athletic function is
      tendon damage. POTENTIAL RELEVANCE: This study supports anecdotal evidence that
      early treatment of synovial sepsis improves the prognosis for return to intended
      use. It also provides information on prognostic indicators including extent of
      damage to collateral structures.

PMID- 15460079
TI  - Molecular characterisation of fructose transport in equine small intestine.
AB  - REASONS FOR PERFORMING STUDY: Fructose can be a suitable carbohydrate supplement
      for horses before and/or during endurance exercise. In comparison to glucose, the
      ingestion of fructose results in a lower insulin peak and less marked
      fluctuations in blood glucose during exercise, potentially avoiding hypoglycaemia
      induced exhaustion. OBJECTIVES: To assess the capacity of the equine small
      intestine to absorb fructose and to determine the mechanism, molecular structure
      and properties of equine intestinal fructose transport. METHODS: Using PCR-based
      strategies, RNA isolated from equine small intestine and primers designed to
      homologous regions of the fructose transporter, GLUT5, cDNA of other species, we
      cloned and sequenced equine GLUT5 (eGLUT5). Northern and western blot analyses,
      in conjunction with immunohistochemistry, utilising eGLUT5 cDNA and antibodies,
      assessed expression of eGLUT5 along the longitudinal and radial axes of the small
      intestine. Functional properties of fructose transport in intestinal brush-border
      membrane vesicles were measured using the rapid-filtration technique. RESULTS:
      eGLUT5 is expressed in the villus enterocytes with highest levels in
      duodenum>jejunum and lowest in the ileum. Kinetic studies indicate eGLUT5 is a
      low affinity, high capacity transporter. CONCLUSIONS: Equine small intestine has
      the capacity to absorb fructose. POTENTIAL RELEVANCE: The molecular probes
      produced in these studies can be used as diagnostic aids to determine equine
      intestinal monosaccharide malabsorption.

PMID- 15460080
TI  - Immunoexpression of androgen receptors in testes of immature and mature
      stallions.

PMID- 15460081
TI  - Complication of partial stylohyoidectomy for treatment of temporohyoid
      osteoarthropathy and an alternative surgical technique in three cases.

PMID- 15460082
TI  - Hepatitis E: Chad, Sudan.

PMID- 15460083
TI  - Overview of the WHO framework for monitoring and evaluating surveillance and
      response systems for communicable diseases.

PMID- 15460084
TI  - Wider participation required in HIV vaccine clinical trials.

PMID- 15460085
TI  - Are at-home treatments for warts effective?

PMID- 15460086
TI  - Cardiovascular risk beyond LDL-C levels. Other lipids are performers in
      cholesterol story.
AB  - High levels of low-density lipoprotein cholesterol (LDL-C) are an obvious culprit
      in coronary artery disease (CAD). However, the search for lipid factors that
      influence cardiovascular health does not end there. In this article, Dr Nash
      presents the various lipid factors involved, for better or worse, in CAD. He
      emphasizes that although studies have expanded the understanding of this disease,
      the knowledge needs to be put to use more consistently in clinical practice in
      order to provide optimal patient care.

PMID- 15460087
TI  - Three common neuralgias. How to manage trigeminal, occipital, and postherpetic
      pain.
AB  - The pain experienced by patients with trigeminal, occipital, or postherpetic
      neuralgia is often severe, chronic, and difficult to treat. In this article, Drs
      Ashkenazi and Levin outline the pathologic mechanisms of pain in these common
      neuralgias and discuss individually tailored pharmacologic and surgical
      approaches to their treatment.

PMID- 15460088
TI  - Opioids for chronic noncancer pain. Tailoring therapy to fit the patient and the
      pain.
AB  - Opioids are powerful medications with a history that includes use for pain relief
      and, at times, addiction. This history of therapy versus drug abuse continues to
      cloud their prescription today, despite reports of effective treatment for the
      chronic pain that certain diseases can bring. Here, Drs Antoin and Beasley review
      the use of opioid agents in medicine, highlight the importance of proper patient
      selection and education in their use, and convey how opioids can be a viable
      option today for successful therapy for chronic noncancer pain.

PMID- 15460089
TI  - Changing the face of pain management. Mechanism-based treatment most likely to
      succeed.
AB  - A 48-year-old mechanic presented to his new primary care physician with
      complaints of ongoing neck and upper back pain. He had sustained a neck injury
      while at work 3 years earlier. Magnetic resonance imaging revealed a herniated C5
      6 disk resulting in moderate spinal stenosis and right foraminal encroachment.
      Persistent pain in the right arm and scapula prompted physical therapy and
      pharmacologic treatment, neither of which was helpful. Epidural corticosteroid
      treatment was only transiently effective.

PMID- 15460090
TI  - A primary care approach to Sjogren's syndrome. Helping patients cope with sicca
      symptoms, extraglandular manifestations.
AB  - Sjogren's syndrome is a chronic, systemic, autoimmune inflammatory disorder
      characterized by lymphocytic infiltration of exocrine glands, most notably the
      salivary and lacrimal glands. It results in loss of functional epithelium,
      diminished exocrine function, and gradual onset of dryness of the eyes, mouth,
      and other body parts (sicca syndrome). Because most patients with Sjogren's
      syndrome are female, this syndrome also represents a major women's health problem
      that is often misdiagnosed and undertreated. In this article, Drs Derk and Vivino
      review the criteria for diagnosis, common signs and symptoms, and strategies for
      increasing patient comfort.

PMID- 15460091
TI  - Dermatitis associated with henna tattoo. "Safe" alternative to permanent tattoos
      carries risk.

PMID- 15460092
TI  - Patient notes: Plantar fasciitis.

PMID- 15460093
TI  - Senator Harkin's HeLP (healthy lifestyle and prevention) America Act (s2558).

PMID- 15460094
TI  - Health care, not sick care.
AB  - Senator Tom Harkin announces his introduction of the HeLP (Healthy Lifestyles and
      Prevention) Act. This comprehensive legislation provides incentives to stimulate
      health promotion in workplace, school, and community settings, with specific
      programs for disabled people, food marketing, Medicare reimbursement for
      preventive services, and research on obesity, and creation of a National Health
      Promotion Trust Fund to pay for programs by penalties on tobacco companies that
      fail to cut smoking rates among children, ending federal subsidies for tobacco
      advertising, and closing other tax loopholes.

PMID- 15460095
TI  - Outcomes of a statewide anti-tobacco industry youth organizing movement.
AB  - PURPOSE: To outline the design and present select findings from an evaluation of
      a statewide anti-tobacco industry youth organizing movement. DESIGN: A telephone
      survey was administered to teenagers to assess associations between exposure to
      anti-industry youth organizing activities and tobacco-related attitudes and
      behaviors. A group-level comparison between areas high and low in youth
      organizing activities was planned. Methodological obstacles necessitated a
      subject-level analytic approach, with comparisons being made between youth at
      higher and lower levels of exposure. SETTING: Six rural areas (comprising 13
      counties) and two urban regions of Minnesota were selected for survey. SUBJECTS:
      The study comprised 852 youth, aged 15 to 17 years old, randomly selected from
      county-specific sampling frames constructed from a marketing research database.
      MEASURES: Exposure index scores were developed for two types of activities
      designed to involve youth in the anti-industry program: branding (creating
      awareness of the movement in general) and messaging (informing about the
      movement's main messages). Attitudinal outcomes measured attitudes about the
      tobacco industry and the effectiveness of youth action. Behavioral outcomes
      included taking action to get involved in the organization, spreading an anti
      industry message, and smoking susceptibility. RESULTS: Branding index scores were
      significantly correlated with taking action to get involved (p < or = .001) and
      spreading an anti-industry message (p < or = .001). Messaging index scores were
      significantly correlated with all five attitudinal constructs (all associations,
      p < or = .001), taking action to get involved (p < or = .001), and spreading an
      anti-industry message (p < or = . 01). The hypothesized association between
      messaging scores and susceptibility was not significant. CONCLUSION: A youth
      organizing effort, in combination with an intensive countermarketing media
      campaign, can be an effective strategy for involving youth in tobacco prevention
      and generating negative attitudes about the industry.

PMID- 15460096
TI  - The association between multiple youth assets and sexual behavior.
AB  - PURPOSE: To investigate the possible positive cumulative effects that youth
      assets may have on youth sexual behaviors. DESIGN: Cross-sectional data were
      collected from a randomly selected population by in-home, in-person interviews.
      Mantel-Haenszel chi-square test and logistic regression were conducted to
      determine the potential cumulative effects that youth assets may have on youth
      sexual behaviors and to test for significant asset by sexual risk behavior
      trends. SETTING: Racially diverse inner-city neighborhoods in two midwestern
      cities. Subjects. Teenagers (n = 1350; mean age = 15.2 years) and parents of the
      teenagers (n = 1350). The response rate was 51%. MEASURES: Demographic factors,
      nine youth assets, and five sexual behavior outcomes. RESULTS: Significant (p <
      .05) trends and odds ratios (ORs) were found for three of the five youth sexual
      behavior outcomes. Youths with more assets were more likely to have never
      participated in sexual intercourse (OR = 1.32). Of sexually active youths, those
      with more assets were more likely to have delayed first intercourse until at
      least 17 years of age (OR = 1.47) and to have used birth control at last sexual
      intercourse (OR = 1.18). Nonsignificant (p > .05) results were found for current
      sexual activity and number of sexual partners. CONCLUSIONS: The results generally
      support the notion that the more assets adolescents possess, the more likely they
      are to engage in positive behavior. Practitioners planning asset-based teenage
      pregnancy prevention programs might consider promoting several specific youth
      assets.

PMID- 15460097
TI  - Changing patterns in health behaviors and risk factors related to chronic
      diseases, 1990-2000.
AB  - PURPOSE: Assess changes in chronic disease-related health behaviors and risk
      factors from 1990 to 2000, by race/ethnicity, age, and gender. DESIGN: Stratified
      cross-sectional design. SETTING: United States. SUBJECTS: 16,948 black, 11,956
      Hispanic, and 158,707 white women and men, ages 18 to 74. MEASURES: Cigarette
      smoking, obesity, sedentary behavior, low vegetable or fruit intake. From the
      Behavioral Risk Factor Surveillance System. RESULTS: Young women and men, ages 18
      to 24, had poor health profiles and experienced adverse changes from 1990 to
      2000. After the variables were adjusted for education and income, these young
      people had the highest prevalence of smoking (34%-36% current smokers among white
      women and men), the largest increases in smoking (10%-12% increase among white
      women and men; 9% increase among Hispanic women), and large increases in obesity
      (4%-9% increase, all gender and racial/ethnic groups). Young women and men from
      each racial/ethnic group also had high levels of sedentary behavior
      (approximately 20%-30%) and low vegetable or fruit intake (approximately 35%
      50%). In contrast, older Hispanic women and men and older black men, ages 65 to
      74, showed some of the most positive changes. They had the largest decreases in
      smoking (Hispanic women), largest decreases in sedentary behavior (Hispanic women
      and black men), and largest increases in vegetable or fruit intake (Hispanic
      women and men, and black men). CONCLUSION: The poor and worsening health profile
      of young women and men is a particular concern, as they will soon enter the ages
      of high chronic disease burden.

PMID- 15460098
TI  - The STRENGTH Ezine: an application of e-mail for health promotion in adolescent
      girls.
AB  - PURPOSE: Few studies have investigated the efficacy of e-mail for promoting
      behavior change. This study evaluates the participation in and outcomes
      associated with an e-mail-based health promotion program. METHODS: Adolescent
      girls aged 15 to 17 years were recruited at a shopping mall. Participants with an
      e-mail address were assigned to the interactive e-mail magazine (Ezine) group (n
      = 37), whereas those not reporting an e-mail address were assigned to the non
      Ezine group (n = 33). Participants in the Ezine group received the health Ezine,
      which included a quiz and an advice column, on a weekly basis. RESULTS: Results
      indicate that among the Ezine group, there was a high recall of the Ezine
      (81.1%), and more than one third of the participants replied to Ezine volumes
      with quiz answers or an advice question (36.6%). Differences in health behavior
      change between the Ezine and non-Ezine groups were not significant. CONCLUSIONS:
      E-mails on health-related matters can generate moderate levels of involvement in
      adolescent girls. Given the widespread use of e-mail, more studies are needed on
      the effective application of e-mail for health behavior change.

PMID- 15460099
TI  - A schematic for focusing on youth in investigations of community design and
      physical activity.
AB  - This paper provides a first step in addressing special considerations for youth
      in a relatively new area of physical activity research. After reviewing the
      urgent need for novel approaches to increasing physical activity, the growing
      interest in the effects of community design are discussed. Although most
      discussion on this topic has focused on adults, there are important differences
      between youth and adults that warrant a special focus on youth and need to be
      accounted for This article presents a schematic that accounts for how and where
      youth spend their time, decomposing the day into time spent in travel and time
      spent at destinations, and identifying portions of those times that are spent
      engaged in physical activity. By focusing on both spatial and behavioral
      dimensions of youth time, the schematic may help organize and advance scientific
      inquiry into the relationships between community design and physical activity
      specifically for youth.

PMID- 15460100
TI  - When worlds collide: observations on the integration of epidemiology and
      transportation behavioral analysis in the study of walking.
AB  - Since obesity has emerged as a public health crisis in the United States, the
      factors that influence physical activity are of interest to both epidemiologists
      and transportation researchers. This article describes different approaches taken
      by the two disciplines to this issue. "Utilitarian" walking to accomplish a task,
      as opposed to structured exercise, could be a highly sustainable way for people
      to achieve recommended levels of physical activity. Transportation planners have
      begun to investigate factors of urban form and transportation services that
      influence the choice to walk. Epidemiologists have become more aware of the
      importance of factors in the built and social environment that could influence
      health behaviors like walking. Few transportation studies focus on the generation
      of the utilitarian walk trip as the key variable; rather, they include it in more
      general discussions of urban form. Likewise, most epidemiologic studies have not
      focused on utilitarian walking, but have folded it into an overall measure of
      physical activity that emphasizes structured exercise. Further transportation
      research should examine the effects of improved mobility services in addition to
      alterations of the built environment. Integration of epidemiologic and
      transportation behavioral research could enhance our understanding of the role of
      urban and transportation factors on physical activity.

PMID- 15460101
TI  - Urban form and older residents' service use, walking, driving, quality of life,
      and neighborhood satisfaction.
AB  - PURPOSE: This study explored the relationship between pedestrian-friendly urban
      form as reflected in new urbanism design guidelines, and neighborhood service
      use, walking, driving, quality of life, and neighborhood satisfaction among older
      women. DESIGN: A cross-sectional survey compared residents of census tracts
      similar indemographic characteristics but differing in urban form. SETTING: The
      setting was urban and suburban areas of Portland, Oregon. SUBJECTS: The sample
      consisted of 372 females living alone over age 70 in six census tracts; 133 (36%)
      completed surveys. MEASURES: The New Urbanism Index rated the physical features
      of respondents' neighborhoods. The Neighborhood Resident Survey assessed travel
      modes and neighborhood satisfaction. The Quality of Life Index measured resident
      well-being. The Dartmouth COOP Functional Health Charts measured health status.
      Group comparisons were made with t-tests and regression analysis. RESULTS:
      Although limited by the cross-sectional design, the study showed that new
      urbanism partially explained several differences in service use and activity:
      distance to a grocery store (r2 change = .11, p = .001), number of services used
      within 1 mile from home (r2 change = .06, p = .007), number of walking activities
      (r2 change = .08, p = .001), number of services accessed by walking (r2 change =
      .14, p = .000), and number of services accessed by driving (r2 change = .05, p =
      .001). CONCLUSIONS: Traditional urban neighborhoods with mixed services and good
      pedestrian access were associated with increased walking among older residents.

PMID- 15460102
TI  - Reducing obesity in work organizations.
AB  - The problem of overweight and obesity has been called an emerging "public health
      epidemic" of major proportions. In this issue of The Art of Health Promotion the
      focus is on the magnitude of the problem for employers and possible interventions
      that can help reduce obesity in working populations. Thirty-five possible
      intervention strategies from the "least invasive" to the "most invasive" are
      identified. Issues of cost, economic effectiveness and relative invasiveness are
      addressed in the ordering of the possible interventions. Finally a set of metrics
      are suggested for measuring the trends and effects of the use of multiple
      interventions targeted on obesity within a particular work force.

PMID- 15460103
TI  - Ageing-induced changes in the cortical granules of mouse eggs.
AB  - The cortical cytoplasm and cortical granules (CGs) of mouse oocytes were analysed
      by electron microscopy. Oocytes were collected soon and 20h after ovulation from
      adult young females (3-4 months old). In addition, gametes collected soon after
      ovulation from 12- to 14-month-old females were used. Ultrastructural analyses
      were undertaken using the conventional procedures and the alcoholic PTA method.
      PTA selectively stains the CGs indicating the presence of lysine-rich proteins in
      these granules. Oocytes from young females showed CGs as dense granules 300-500
      nm in diameter linearly arranged under the oolemma. In oocytes recovered 20h
      after ovulation 24.31% of CGs appeared vacuolated and 38.40% internalized in the
      cytoplasm. In gametes collected from old females several changes were observed in
      the cortical cytoplasm: (a) CGs appeared concentrated in some areas while others
      regions were devoid of granules; (b) groups of CGs appeared internalized in the
      egg cytoplasm; (c) the CG contents had swollen and changed, showing dense and
      clear areas; (d) numerous dense structures and vesicles (lysosome-like vesicles)
      were present; (e) cytoplasmic fragmentation was frequently seen. Fragments
      contained CGs, dense structures and vacuoles. These changes are closely related
      to the low fertilization rates shown by these oocytes when they were used for in
      vitro fertilization procedures.

PMID- 15460104
TI  - Activity of exoglycosidases in ejaculated spermatozoa of boar and bull.
AB  - The activity of exoglycosidases in extracts from freshly ejaculated boar and bull
      spermatozoa with 0.2% Brij-35/2% acetic acid was measured. The results show that
      beta-N-acetylhexosaminidase, beta-galactosidase and alpha-mannosidase are the
      major glycosidases; much higher levels of activity were found in boar spermatozoa
      than in bull spermatozoa. When compared on a per spermatozoon basis, the ratios
      of the activities of beta-N-acetylhexosaminidase, beta-galactosidase and alpha
      mannosidase in boar spermatozoon relative to those in bull spermatozoon were
      approximately 13000:1, 1700:1 and 400:1, respectively. Liberation of these
      glycosidases from bull spermatozoa by treatment with phosphatidylinositol
      specific phospholipase C (PI-PLC) was low, in contrast to liberation of alpha
      mannosidase from boar spermatozoa previously found by the same means. The
      possibility that the exoglycosidases present in large amounts in boar spermatozoa
      play a role in the process of binding to the zona pellucida glycoprotein of the
      egg is discussed.

PMID- 15460105
TI  - Use of mouse oocytes to evaluate the ability of human sperm to activate oocytes
      after failure of activation by intracytoplasmic sperm injection.
AB  - The objective of the present study was to investigate the nuclei of human sperms
      that failed to fertilize human oocytes after intracytoplasmic sperm injection
      (ICSI). The sperms were injected into mouse oocytes by a piezo-micromanipulator,
      and some of these oocytes were artificially activated with strontium chloride
      (SrCl2) after ICSI. The oocytes were fixed, stained, and subjected to chromosomal
      analysis. The survival rate of mouse oocytes injected with infertile human sperms
      was 92.0% (46/50), while that of the control mouse oocytes injected with fertile
      human sperms was 73.6% (81/110). The rate of two pronuclei (2PN) formation was 0
      (0/46) by the infertile sperms and 81.5% (66/81) by the fertile ones, a
      significant difference (p < 0.01). Sperm chromosomes in non-activated oocytes
      were present as premature chromosome condensation (PCC). Artificial activation
      after ICSI increased the 2PN formation rate in the infertile group to 90.3%
      (28/31). The results of the present study suggest that infertile sperms have a
      low potential to spontaneously activate oocytes and to form pronuclei. Thus,
      artificial activation after ICSI may rescue oocytes fertilized with infertile
      human sperms that do not produce 2PN. The present study proved the usefulness of
      mouse oocytes as specimens in evaluating the oocyte-activating capacity of
      objective human sperms prior to ICSI treatment.

PMID- 15460106
TI  - Antioxidant supplementation of boar spermatozoa from different fractions of the
      ejaculate improves cryopreservation: changes in sperm membrane lipid
      architecture.
AB  - Previous studies have shown sperm quality after cryopreservation differs
      depending on the fraction of seminal plasma the boar spermatozoa are contained
      in. Thus, spermatozoa contained in the first 10 ml of the sperm-rich fraction
      (portion I) withstand handling procedures (extension, handling and
      freezing/thawing) better than those contained in the latter part of a
      fractionated ejaculate (second portion of the sperm-rich fraction and the post
      spermatic fraction; portion II). The present study evaluated whether an exogenous
      antioxidant, the water-soluble vitamin E analogue Trolox (6-hydroxy-2,5,7,8
      tetramethylchroman-2-carboxylic acid), could, when added to the freezing extender
      in a split-sample design trial, improve the post-thaw viability and membrane
      quality of this particular portion of the ejaculate, with particular attention to
      the status of the plasma membrane. Using a split-sample design, the initial
      changes in the fluidity status of the sperm plasmalemma after thawing were
      measured by flow cytometry (FC) after loading with Merocyanine-540 and YO-PRO-1.
      The FC-derived data revealed a clear ejaculate portion-dependent effect of the
      antioxidant supplementation. While no beneficial effect of the antioxidant
      supplementation was visible in spermatozoa from portion I, more spermatozoa with
      intact membranes were observed in the supplemented samples of portion II,
      suggesting the protective effect of vitamin E is dependent of the portion of the
      boar ejaculate considered.

PMID- 15460107
TI  - Relationship between the appearance of preantral follicles in the fetal ovary of
      Antarctic minke whales (Balaenoptera bonaerensis) and hormone concentrations in
      the fetal heart, umbilical cord and maternal blood.
AB  - The present study aimed to determine the relationship among changes in the number
      of preantral follicles and concentrations of follicle-stimulating hormone (FSH),
      luteinizing hormone (LH), progesterone (P4), androstenedione (A) and estradiol
      17beta (E2) in the fetal heart, umbilical cord and maternal blood. Primordial
      follicles had already appeared in a 20 cm fetus and primary follicles were
      observed in a 50 cm fetus. In a 70 cm fetus, the number of primordial and primary
      follicles increased rapidly and secondary follicles were present. The
      concentrations of LH and FSH did not change between 20 cm and 160 cm in fetal
      length. When the fetal length became > 70 cm, serum levels in the fetus,
      umbilical cord and mothers, and E2 levels in umbilical cord increased
      synchronously (p < 0.05). These results showed increases in the number of
      preantral follicles in the Antarctic minke whale fetal ovary along with fetal
      growth during the early gestation period. These findings suggest that the change
      in preantral follicles was associated with changes in the concentration of
      steroids in early gestation periods. The changes in steroid concentrations in the
      fetal and umbilical cord blood and the increased number of preantral follicles
      were coincident at around 70 cm in fetal length, whereas the growth and
      differentiation of primordial and primary follicles appeared to be independent of
      FSH and LH.

PMID- 15460108
TI  - Effects of the time interval between fusion and activation on in vitro rabbit
      nuclear transfer efficiency when nuclear donor cells are derived from older
      adults.
AB  - Cloning older adult rabbits can serve as a model in animal breeding, biodiversity
      preservation and in human therapeutic cloning. To establish the required exposure
      time of fibroblasts from these kind of animals to reprogramming factors, in the
      present study three different time intervals between fusion and activation were
      tested (30 min, 30-ADF group; 60 min, 60-ADF group; and 90 min, 90-ADF group).
      Vitrified epithelial fibroblasts derived from four older adult rabbit females
      (D1, D2, D3 and D4) and cultured from passages 0 to 4 were used as nuclear
      donors. Nuclear status of reconstructed embryos was not evaluated. No differences
      were observed in blastocyst rate (30-ADF 21% vs 60-ADF 19% vs 90-ADF 18%).
      Differences in hatching rates did not reach significance (30-ADF 11% vs 60-ADF
      18% vs 90-ADF 18%). However, in the 60- and 90-ADF groups, embryos reached the
      blastocyst stage earlier than in the 30-ADF group (day 4: 40% and 50% vs 8%; p >
      0.05). Moreover, the quality of blastocysts (good vs poor) was lower in the 30
      ADF group (good: 30-ADF 38% vs 60-ADF 90% vs 90-ADF 90%; p > 0.05). Overall,
      these results suggest an unfavourable effect of the shortest exposure time tested
      (30 min). Differences between specimen origins were detected (blastocyst and
      hatching rates: D2 (26%; 25%) and D4 (25%; 27%) vs D1 (10%; 11%) and D3 (12%;
      12%)), but significance were not reached. Effect of culture passage was not
      detected in any parameter studied.

PMID- 15460109
TI  - Additional effect of epidermal growth factor during in vitro maturation for
      individual bovine oocytes using a chemically defined medium.
AB  - This study was performed to establish an individual bovine oocyte-IVP system
      using a chemically defined simple medium (mSOFaa containing 1 mg/ml polyvinyl
      alcohol: PVA) and to investigate the effects of epidermal growth factor (EGF)
      during oocyte maturation on in vitro maturation, fertilization and embryonic
      development. Cumulus-oocyte complexes were collected from bovine ovaries and were
      matured in mSOFaa containing PVA (control medium) supplemented with 0, 1, 10 or
      50 ng/ml of EGF. Two further groups (TCM199 and mSOFaa, supplemented with 10%
      fetal calf serum were also included. In this study, mSOFaa containing PVA were
      used as a basic medium for fertilization and embryo development in vitro.
      Experiments were conducted in both group- and individual-IVP systems. In the
      group-IVP system, the proportion of matured oocytes (MII) in the control medium
      (62.7% +/- 5.0%) was significantly (p < 0.05) lower than in all other treatments,
      and in the individual-IVP system, the addition of 1 ng/ml EGF significantly (p <
      0.05) increased the maturation rate (1 ng/ml EGF vs control: 76.2% +/- 5.4% vs
      57.1% +/- 14.4%). The addition of EGF did not affect the proportions of
      penetrated and normally fertilized oocytes in either individual- or group-culture
      systems. In the group-IVP system, no significant difference among treatments was
      found in the rate of blastocyst formation, whereas in the individual-IVP system
      the control medium supplemented with 10 ng/ml EGF resulted in a significantly (p
      < 0.05) higher the rate of blastocyst formation (20.0 +/- 5.2%) than that in the
      control medium (6.2% +/- 3.5%). These results indicate that bovine oocytes can
      successfully develop to blastocysts in an individual-IVP system using a single
      chemically defined medium, and that the group-IVP system also resulted in a
      similar level of blastocyst formation to that in a standard multiple-media system
      in our laboratory. The effect of EGF during oocyte maturation medium differed
      depending on whether embryos were cultured individually or in groups.

PMID- 15460110
TI  - Murine Asb-17 expression during mouse testis development and spermatogenesis.
AB  - In this study we isolated a murine mAsb-17 from mouse testis by RT-PCR using
      primers designed based on the sequences from the GenBank database. The sequence
      analysis showed that mAsb-17 encodes a 295 amino acid polypeptide with a
      molecular weight of approximately 34 kDa containing two ankyrin repeats and one
      SOCS box. The amino acid sequence of mASB-17 showed 87.5%, 98.3% and 92.9%
      identity with that of human, rat and dog, respectively. Interestingly, northern
      blot analysis showed that mAsb-17 was expressed only in the testis. The
      expression analysis by RT-PCR for mAsb-17 in mouse indicates that mAsb-17 is
      expressed from the fourth week after birth to adult, with the highest expression
      in round spermatids. Both northern blot and RT-PCR analyses suggest that mASB-17
      may play essential roles in testis development and spermatogenesis.

PMID- 15460111
TI  - Effect of proteasome inhibitor MG132 on in vitro maturation of pig oocytes.
AB  - The present study aimed to demonstrate the dependence of meiotic maturation in
      pig oocytes on the activity of the protease complex proteasome. The proteasome
      inhibitor MG132 blocked the exit of maturing pig oocytes from metaphase I stage.
      Seventy-five per cent of the oocytes were blocked at metaphase I when they were
      cultured with 10 microM MG132. The blocking effect of MG132 was expressed only
      when the oocytes were exposed to an inhibitor before the 18th hour of in vitro
      culture. The effects of MG132 are fully reversible. However, a significant
      proportion of oocytes (46%) cultured for 48 h in MG132-supplemented medium and
      then for 24 h in MG132-free medium did not block meiosis at the stage of
      metaphase II and underwent spontaneous parthenogenetic activation. On the basis
      of our data we can conclude that exit from the metaphase I stage of meiosis is
      proteasome-dependent in pig oocytes matured in vitro. On the other hand, our data
      also indicate that other proteasome-independent events are involved in regulating
      the exit from metaphase I.

PMID- 15460112
TI  - Reconstruction of enucleated mouse germinal vesicle oocytes with blastomere
      nuclei.
AB  - We have investigated the possibility that mitotic nuclei originating from
      preimplantation stage embryos and placed in the oocyte cytoplasm can undergo
      remodelling that allows them to undergo meiosis in the mouse. To address this
      question, we have used enucleated germinal vesicle (GV) ooplasts as recipients
      and blastomeres from the 2-, 4- or 8-cell stage as nuclear donors. We employed
      two methods to obtain ooplasts from GV oocytes: cutting and enucleation. Although
      efficiency of the reconstruction process was higher after enucleation than after
      cutting (90% and 70% respectively), the developmental potential of the oocytes
      was independent of how they had been produced. Nuclei from the 2-, 4-, or 8-cell
      stage embryos supported maturation in about 35%, 55% and 60% of cases,
      respectively. The time between nuclear envelope breakdown and the first meiotic
      division was shortened by up to 5 h in reconstructed oocytes, a period equivalent
      to the mitotic division of control blastomeres. About one-third of oocytes
      reconstituted with blastomere nuclei divided symmetrically instead of extruding a
      polar body; however, in the majority of them metaphase plates were found,
      suggesting that reconstructed oocytes (cybrids) underwent a meiotic rather than
      mitotic division. The highest percentage of asymmetric divisions accompanied by
      metaphase plates was found in cybrids with 8-cell-stage blastomere nuclei,
      suggesting that the nuclei from this stage appear to conform best to the
      cytoplasmic environment of GV ooplasts. Our results indicate that the oocyte
      cytoplasm is capable of remodelling blastomere nuclei, allowing them to follow
      the path of the meiotic cell cycle.

PMID- 15460113
TI  - Mitochondrial lipids in Bufo arenarum full-grown oocytes.
AB  - Both the content and composition of polar and neutral lipids from the
      mitochondrial fraction of ovarian full-grown Bufo arenarum oocytes were analysed
      in the present study. Triacylglycerols (TAG) represent 33% of the total lipids,
      followed by phosphatidylcholine (PC), free fatty acids (FFA) and
      phosphatidylethanolamine (PE). Diphosphatidylglycerol (DPG) or cardiolipin, a
      specific component of the inner mitochondrial membrane, represents about 4% of
      the total lipid content. Palmitic (16:0) and arachidonic (20:4n6) acids are the
      most abundant fatty acids in PC and PE, respectively. DPG is enriched in fatty
      acids with carbon chain lengths of 18, the principal component being linoleic
      acid. In phosphatidylinositol (PI), 20:4n6 and stearic acid (18:0) represent
      about 72 mol% of the total acyl group level. The main fatty acids in TAG are
      linoleic (18:2), oleic (18:1), and palmitic acids. The fatty acid composition of
      FFA and diacylglycerols (DAG) is similar, 16:0 being the most abundant acyl
      group. PE is the most unsaturated lipid and sphingomyelin (SM) has the lowest
      unsaturation index.

PMID- 15460114
TI  - Somatic nucleus remodelling in immature and mature Rassir oocyte cytoplasm.
AB  - Successful production of cloned animals derived from somatic cells has been
      achieved in sheep, cattle, goats, mice, pigs, rabbits, etc. But the efficiency of
      nuclear transfer is very low in all species. The present study was conducted to
      examine somatic nucleus remodelling and developmental ability in vitro of rabbit
      embryos by transferring somatic cells into enucleated germinal vesicle (GV),
      metaphase I (MI) or metaphase II (MII) oocytes. Microtubules were organized
      around condensed chromosomes after the nucleus had been transferred into any of
      the three types of cytoplasm. A bipolar spindle was formed in enucleated MII
      cytoplasm. Most of the nuclei failed to form a normal spindle within GV and MI
      cytoplasm. Some chromosomes scattered throughout the cytoplasm and some formed a
      monopolar spindle. Pseudopronucleus formation was observed in all three types of
      cytoplasm. Reconstructed embryos with MI and MII cytoplasm could develop to
      blastcysts. Nuclei in GV cytoplasm could develop only to the 4-cell stage. These
      results suggest that (1) GV material is important for nucleus remodelling after
      nuclear transfer, and (2) oocyte cytoplasm has the capacity to dedifferentiate
      somatic cells during oocyte maturation.

PMID- 15460115
TI  - Update: heterosexual transmission of HIV.

PMID- 15460116
TI  - [AIDS: a new combat strategy].

PMID- 15460117
TI  - [Ten years of experience in the management of HIV/AIDS at the Ambulatory
      Treatment Centers of the OPALS and French Red Cross].

PMID- 15460118
TI  - [First International Brazzaville Congress on the tse-tse fly and trypanosomiasis.
      March 23-25, 2004].

PMID- 15460138
TI  - [New form of hemorraghic fever in Zaire].
AB  - The purpose of this report is to describe the events that occurred immediately
      before and during the first weeks of the Ebola virus epicemic in the Democratic
      Republic of the Congo (formerly Zaire) in September and October 1976. By October
      4 Dr Raffier and Dr Ruppol were already on hand at the epicenter of the epicemic
      in the Equator region about 1000 km from Kinshasa. They had been mandated by the
      State Health Commissioner to conduct a firsthand assessment of the reportedly
      disastrous local conditions and to implement emergency measures necessary to
      reassure the population. It was immediately understood to take all steps to
      prevent mass migration and to collect specimens necessary for rapid
      identification of the cause of an exceptionally serious crisis situation.
      Traveling by plane and helicopter the two physicians went to the cities of Bumba
      and Lissala as well as to many surrounding villages including Yambouku where the
      first case was reported. Upon returning to Kinshash on October 9, specimens were
      sent to the CDC in Atlanta where the offending virus was identified. Authorities
      in Paris and Bruxelles were alerted of the emergency in order to secure the
      assistance of various specialists incuding virologists, epidemiologists,
      biologists and entomologists. Most of the new staff arrived on October 23 and
      were joined by colleagues from the United States, Belgium, and Canada as well as
      one specialist from South Africa on October 30. These experts were then able to
      form an International Medical Comission for an in depth assessment of this new
      epidemic outbreak.

PMID- 15460139
TI  - [Serogroup W135 meningococcal meningitis, four years after the epidemic of 2000].

PMID- 15460140
TI  - [Buruli ulcer in 2004].

PMID- 15460141
TI  - [Virological surveillance of acute flaccid paralysis in Democratic Republic of
      Congo from 1997-2001].
AB  - The purpose of this report is to describe the results of virological surveillance
      of acute flaccid paralysis (AFP) in Democratic Republic of Congo (DRC), a war
      torn country. A total of 3658 stool samples were collected from patients with AFP
      in provinces under government control and processed as recommended by WHO. The
      number of specimens tested increased from 32 in 1997 to 2471 in 2001 as the
      national epidemiologic surveillance program for AFP improved. The national
      reference laboratory accredited in 1999 was appraised on the basis of the annual
      rate of non-polio enterovirus isolation which rose from 10% in 1999 to 20% in
      2001 and by the percentage of lab results reported within 28 days which rose from
      50% in 1999 to over the 80% threshold required by WHO in 2001. From 1997 to 2001,
      68 strains of wild poliovirus were isolated including 52 type 1 strains, one type
      2 strain and 15 type 3 strains. Most cases of poliomyelitis (81%) reported
      between 1997 and 2001 involved children aged 0 to 5 years. Only 12% of cases
      involved children aged 6 to 14 years and 3% involved young adults. Sixty-seven
      percent of the 45 poliomyelitis patients with documented vaccine status had
      received 0 to 3 doses of oral poliovirus vaccine (OPV). Fifteen children (33%)
      developed the disease despite having received more than 4 required doses of OPV.
      Since 1997 three provinces of DRC, ie., Bas-Congo, Kinshasa city and Nord-Kivu,
      have been free of wild poliovirus. In 2001 wild poliovirus circulation had been
      stopped throughout the country thanks to implementation of routine immunization
      and especially of the national immunization days (NIDs) program.

PMID- 15460142
TI  - [Traditional treatment for Buruli ulcer in Benin].
AB  - The purpose of this transversve qualitative study on traditional treatment for
      Buruli ulcer in Benin was to track the treatment itinerary of patients, the main
      phases of traditional treatment, cost and efficacy of such treatment, and the
      knowledge and skills of traditional practitioners. A total of 20 traditional
      practitioners, 35 patients treated by traditional therapy, and 35 patients
      treated by surgery were included. Findings showed that both traditional and
      surgical treatment was sought at a late stage. Reasons determining the type of
      treatment chosen included religion, access to adequate care facilities,
      constraints involved in surgical treatment, duration of hospitalization, and fear
      of scarring. The four main steps in traditional treatment were diagnosis, removal
      of necrotic tissue, wound care, and exorcism. The cost of traditional treatment
      was high not only in currency but also by payment in kind (eg., livestock and
      land). Although it is performed with patient consent, traditional treatment
      presents a number of risks. Information campaigns are necessary to inform
      populations about available treatments and the possible risks associated with
      each modality. Care centers must do more to lessen the constraints involved in
      surgical treatment both in terms of duration of hospitalization and cosmetic
      outcome.

PMID- 15460143
TI  - [Plasma selenium and peripartum cardiomyopathy in Bamako, Mali].
AB  - Peripartum heart failure due to unexplained dilated cardiomyopathy is a common
      disorder as Savannak-Sahelian Africa. One of the many suspected risk factors
      identified is selenium deficiency. The purpose of this study was to measure
      plasma selenium levels in patients with peripartum heart failure due to
      cardiomyopathy in Bamako, Republic of Mali and compare data with healthy Sahalian
      women with the same obstetrical status. Plasma selenium was measured in a patient
      group consisting of 28 Malian women presenting peripartum heart failure and in a
      control group of 28 healthy breast-feeding Nigerien women of comparable age. The
      criteria for matching the two groups was parity (similar number of deliveries)
      since multiparity is a risk factor for peripartum cardiomyopathy. The Wilcoxon
      test (nonparametric) was used to compare the 2 groups considering up value < 0.05
      as significant. Plasma selenium was significantly lower in patients from Mali
      than in controls from Niger (65 +/- 17 ng/ml vs. 78 +/- 17 ng/ml, p = 0.01). The
      results of this study showing lower plasma selenium in Bamako patients with
      peripartum cardiomyopathy than in a matching healthy control population confirms
      the previous data from the Niamey study.

PMID- 15460144
TI  - [Late occurrence of first epileptic seizures: a 42-case series].
AB  - Late occurrence of epilepsy is common in tropical areas. This report describes a
      series of 42 cases of late epilepsy collected over a three-year period. Findings
      were consistent with the literature: highest incidence in young age groups,
      predominance of partial symptomatic epilepsy, and wide spectrum of etiologies.
      The most frequent etiology was tumoral disease followed by vascular and
      infectious disease. Brain CT scan and electro-encephalography were highly useful
      for identification of clinical and etiological entities.

PMID- 15460145
TI  - [Particularities of visceral leishmaniasis in adults not infected by HIV in
      Tunisia].
AB  - The incidence of adult visceral leishmaniasis in Tunisia has increased in recent
      years. As a result the epidemiological profile of the disease in our country is
      now closer to those observed in other Mediterranean countries. Most of the
      increase involves adults not infected by human immunodeficiency virus (HIV)
      although 56% of patients presented concurrent disease. In comparison with
      pediatric visceral leishmaniasis, adult disease is characterized by inconsistence
      occurrence of some major symptoms such as fever and spleen enlargement. For this
      reason the clinical disease syndrome may be incomplete and diagnosis may be
      difficult. Laboratory tests are essential for definitive diagnosis. Although no
      test is specific, some findings are highly useful, e.g, elevated g-globulins
      which was observed in 94% of patients in our series. Standard serology is less
      sensitive in adults with 18% of false negatives in our series probably as a
      result of immunodeficiency in some patients.

PMID- 15460146
TI  - [Student sexual behavior at the University of Bangui in the Central African
      Republic].
AB  - Encouraging responsible sexual behavior has become an important issue in recent
      years mainly due to the worldwide human immunodeficiency virus (HIV) epidemic and
      to the high number of unwanted pregnancies that often end in high-risk abortions.
      Young people and in particular students in higher education are high-risk groups
      for both unwanted pregnancy and HIV. The purpose of this report is to describe
      the findings of a month-long survey conducted among students at the University of
      Bangui (UB) in 1998-1999. Individual students were asked to give immediate
      responses to semi-open questions. The Chi test was used to assess correlation
      between a number of variables. A total of 422 UB students including 218 males
      (51.7%) and 204 females (483%) were included in the survey. Mean age was 24.9
      years for females and 26.1 years for males. Over half of the students of both
      sexes reported having their first sexual relation between the ages of 15 and 19
      years. Males were more satisfied by their first experience than females. The
      percent of married students (male or female) was 5.9%. Most students (62.1%) had
      at least 2 sex partners and 58.3% had at least one child. The preferred
      contraceptive method was condom use for males and the Ogino technique for
      females. The percent of female students expressing fear of HIV infection was
      27.4%. The results of this study show that information and education campaigns
      are needed to encourage UB students to practice sexual behavior to avoid both
      unwanted pregnancies and sexually transmitted diseases such as HIV infection.

PMID- 15460147
TI  - [Histoepidemiologic profile of 375 primary bowel cancers at the University
      Hospital Center in Brazzaville, Congo].
AB  - This retrospective study was undertaken to determine the histoepidemiologic
      profile of primary digestive tract cancer based on analysis of 375 of the 2558
      cases diagnosed in the Cytopathology Department of the the University Hospital
      Center in Brazzaville, Congo from January 1992 to December 2001. Incidence was
      14.6%. The sex ratio was 1:5. Age ranged from 39 to 49 years. The liver (40.2%)
      was the most frequent location followed by the colon/rectum (30.2%), stomach
      (26.2%), and esophagus 2.1%. Predisposing factors included low-fiber diet, heavy
      consumption of smoked foods, and history of hepatitis B and C virus infection.
      The most frequent histological entity accounting for 57% of cases was
      adenocarcinoma that was observed in the esophagus, stomach, colon, rectum, and
      pancreas. Systematic screening and treatment of precancerous lesions in high-risk
      patients is necessary to reduce the incidence of digestive tract cancer.

PMID- 15460148
TI  - [Epidemiology of tinea capitis in Abidjan, Cote d'Ivoire].
AB  - Tinea capitis is a dermatosis of the scalp due to dermatophytes that can cause
      hair loss. It remains a significant endemic problem mainly in school children in
      tropical regions. The purpose of this case-control study carried out in the
      Dermatology Center of Treichville Hospital was to identify risk factors for tinea
      capitis in Abidjan, Cote d'Ivoire. A total of 80 cases were recruited on the
      basis of clinical findings showing one or several plaques showing desquamation or
      parakeratosis suggestive of tinea capitis. Diagnosis was confirmed by mycology
      using samples seeded on Sabouraud-chloramphenicol glucose agar and incubated at
      27 degrees C for a mean period of 15 days. Species identification was based on
      growth rate, macroscopic aspect of isolates, production and potential diffusion
      of pigment, and microscopic examination. Controls were the next patient of the
      same age and sex with no evidence of mycosis. All subjects were questioned about
      previous history of mycosis, duration of tinea capitis lesions, functional signs,
      grooming habits, and pet-keeping. Size of selection was calculated by epi info
      6.04 fr according to following estimations: percentage of exposed subjects in
      control group: 30%; percentage of exposed subjects in case group: 50%;
      probability threshold of 5% to find a difference between case and control groups
      even though there was no difference; and probability threshold of 20% to find no
      difference between cases and controls even though there was a difference. Study
      findings demonstrated a 3 times higher incidence of tinea capitis in boys than in
      girls and a peak during childhood especially between the of 5 to 9. The most
      frequent etiologic agents were Trichophyton soudanense and Microsporum
      langeroniise. Subjects at highest risk lived in dwellings having less than 4
      rooms, used soap to wash the hair, cut their hair with a blade, and had low
      income.

PMID- 15460149
TI  - [Diagnostic problems associated with intestinal amoeboma: case report].
AB  - Amoeboma is an inflammatory mass of the colon. It is uncommon with most cases
      occurring in Latin America and South Africa. When amoeboma is the presenting
      symptom of amoebiasis, it poses the problem of differential diagnosis of colon
      cancer. This report describes the case of a 60-year-old patient who presented a
      painful mass in the left hypochondrium. Radiologic and endoscopic examinations
      depicted a ring-like stenosis of the transverse colon in association with a
      mesenteric reaction. The presumptive diagnosis was colon cancer and the patient
      was referred to the National Oncology Institute for surgical treatment.
      Histological examination of the surgical specimen after segmental colectomy
      confirmed diagnosis of intestinal amoeboma. The patient was treated medically
      using metronidazole. Since intestinal amoebiasis is common in our country,
      amoeboma must be considered as a rare but potential diagnosis in patients
      presenting masses of the colon. Differential diagnosis of carcinoma is necessary
      to avoid the risks associated with unnecessary surgery.

PMID- 15460150
TI  - [Extensive bone marrow necrosis as presenting manifestation of sickle cell
      disease in Africa].
AB  - Extensive bone marrow necrosis is a rare but severe complication of sickle cell
      disease. A formerly healthy man was admitted for bone pain, fever, and jaundice
      with severe aregenerative anemia. Bone marrow aspiration and biopsy showed
      extensive bone marrow necrosis while hemoglobin electrophoresis demonstrated
      homozygotic sickle cell disease. Despite early onset of septic arthritis of the
      right shoulder, outcome after blood transfusion and nonspecific treatment was
      favorable. Six months later, hemoglobin level remained stable up to 97 g/L. This
      first African case report illustrates typical features and good prognosis of
      extensive bone marrow necrosis in sickle cell disease. Extensive bone marrow
      necrosis is a highly unusual presenting manifestation of sickle cell in an adult.

PMID- 15460151
TI  - [Cutaneous blastomycosis: description of two cases in Tunisia].
AB  - Blastomycosis is an uncommon mycotic infection in Africa. Isolated cutaneous
      disease is extremely rare. The purpose of this report is to describe 2 cases of
      cutaneous blastomycosis. The first case Involved a 70-year-old rural woman who
      presented papulonodules associated with scars on the upper extremities and right
      leg, ongoing for 2 months. The second patient was a 47-year-old woman who
      presented 2 vegetating plaque areas above the left knee and on the left shoulder,
      ongoing for 4 months. In addition a bow-shaped scar resulting from a dog bite was
      observed. Histologic examination and culture on Sabouraud's medium and brain
      heart agar confirmed diagnosis of cutaneous blastomycosis in both patients. No
      visceral involvement was found. Blastomycosis is uncommon in Tunisia with only 6
      previously published cases. The two cases reported here are interesting because
      involvement was confined to the skin suggesting cutaneous inoculation of
      Blastomyces dermatitidis.

PMID- 15460152
TI  - [Abstract envenomation by the African puff adder (Bitis arietans): value of
      intracompartmental pressure measurement].
AB  - The purpose of this report is to describe a case of severe snake bite with
      envenomation by an African puff adder (Bitis arietans). Presenting symptoms
      warranted administration of antivenon upon admission. The patient's general
      condition improved. However bite-related trauma caused extensive phlyctenuar
      edema of the lower extremity with a high risk of compartimental syndrome due to
      hardening and compression. Due to the high risk for postoperative infection at
      our facility, aponevrotomy to relief pressure was not undertaken immediately.
      Instead management consisted in close surveillance with repeated measurement of
      peripheral pulses by Doppler ultrasound and of intracompartimental pressure. The
      outcome was favorable without need for aponevrotomy. This case demonstrates the
      value of intracompartimental pressure measurement in cases involving this type of
      envenomation in function of available technical facilities.

PMID- 15460153
TI  - [Management of Grave's disease in the tropics (experience at Bouffard Army
      Hospital Center in Djibouti].
AB  - Based on their experience in managing Grave's disease at the Bouffard Army
      Hospital Center within the local health care context in Djibouti, the authors
      advocate surgery as the first line treatment. Medical and economical factors
      supporting this preference are discussed so that readers can adapt them to his
      own local context.

PMID- 15460154
TI  - [Diabetes and amoebiasis: a high-risk combination].
AB  - Amoebiasis is the second most common parasitic disease in the world. It occurs
      mainly in developing countries. Many people in endemic countries are asymptomatic
      carriers. It results in severe disease that can be fatal in rare cases. The case
      described in this report illustrates the growing risk of exposure to amoebiasis
      for diabetic patients as travel to endemic countries becomes more and more
      frequent. In the patient described here amoebiasis led to amoeboma, a rare
      complication of the colonic presentation. Despite a clinical disease syndrome
      mimicking that of an occluding gut tumor, the patient was treated medically with
      drugs alone. Retrospective studies show that diabetics are at higher risk for
      severe complications after amoebic infection. Because of the high incidence and
      severity of concurrent diabetes and amoeba, prophylactic measures are necessary
      for diabetic patients traveling in developing countries.

PMID- 15460155
TI  - [Practical guidelines for the management of Ebola infected patients in the
      field].
AB  - Ebola hemorrhagic fever appears after an incubation of 3 days to 3 weeks. The
      first symptoms are fever accompanied by general and hemorrhagic signs leading to
      death in 50 to 90% of cases. During epidemics definition of cases permits prompt
      diagnosis. Due to the high risk of person-to-person and nosocomial transmission
      associated with Ebola hemorrhagic fever, management is based on isolation of
      patients and institution of protected care. Hands and soiled material are often
      decontaminated using sodium hypochlorite. Patient waste is decontaminated and
      incinerated. Treatment is essentially supportive. There is currently no vaccine
      available. Persons having been in close contact with patient should be kept under
      medical surveillance for 21 days. Recovering patients should use condoms for
      three months. Bodies of deceased patients should be handled by trained teams and
      buried quickly.

PMID- 15460156
TI  - [Nasal carriage of methicillin resistant Staphylococcus aureus in medical care
      providers in Abidjan, Cote d'Ivoire].

PMID- 15460157
TI  - Isolation and characterization of eight pregnancy-associated glycoproteins
      present at high levels in the ovine placenta between day 60 and day 100 of
      gestation.
AB  - Pregnancy-associated glycoproteins (PAG), structurally related to aspartic
      proteinases, are expressed in the outer epithelial cell layer
      (chorion/trophectoderm) of the ungulate placenta. The aim of the present study
      was to isolate as many PAG molecules as possible from placentae collected between
      day 60 and day 100 of gestation and to characterize their amino-terminal amino
      acid sequences. Three heterologous radioimmunoassays were used to monitor PAG
      immunoreactivity throughout the isolation procedures. Sequential use of DEAE
      cellulose, gel filtration, and CM ceramic chromatographies led to the isolation
      of several fractions rich in PAG immunoreactivity. The fractions with a large
      amount of proteins were also purified by chromatofocusing. The analysis of
      immunoreactive fractions by SDS-PAGE, Western blotting and two-dimensional
      electrophoresis followed by amino-terminal microsequencing on PVDF membranes
      allowed to identify eight different ovPAG with apparent molecular masses ranging
      from 55 to 66 kDa and isoelectric points from 4.0 to 6.8. The N-terminal
      sequences were determined and their comparison to those previously identified
      revealed that four of them are identical to those encoded by previously known
      cDNA, while the additional four sequences appear to be novel since they have not
      yet been described.

PMID- 15460158
TI  - Evidence that the photoperiod controls the annual changes in testosterone
      secretion, testicular and body weight in subtropical male goats.
AB  - The aim of this study was to determine whether the reproductive seasonality of
      local male goats from subtropical Mexico (26 degrees N) is controlled by
      photoperiod. The control group (n = 7) remained in an open shed under natural
      daylight. The two experimental groups (n = 6 each) were placed in light-proof
      buildings and exposed for 2 years (yr) to alternations of 3 months (mo) of long
      days and 3 mo of short days. One group was first exposed to long days and the
      other one to short days. Body and testicular weights were determined every 2 wk.
      Blood samples were obtained weekly to determine testosterone plasma
      concentrations. In the control group, the body weight exhibited variations (P <
      0.0001) and it increased during the non-breeding season. In both treated groups,
      long days stimulated weight gain and short days inhibited it (P < 0.0001). In the
      control group, testicular weight displayed variations (P < 0.0001), and high
      values were registered in June. In the treated groups, a testicular weight
      reduction occurred 6-9 mo after the onset of the study. Afterwards, the changes
      in testicular size varied according to daylength (P < 0.01). The pattern of
      plasma testosterone concentration in the control group varied over the study (P <
      0.0001) and the levels were higher from May-June to November. In both treated
      groups, the changes in testosterone secretion occurred according to photoperiod
      changes (P < 0.0001). Short days enhanced testosterone secretion one
      photoperiodic cycle after the onset of the study and long days inhibited it.
      Local male goats from subtropical Mexico are sensitive to photoperiodic changes
      and this environmental cue may control the timing of the breeding season in
      natural conditions.

PMID- 15460159
TI  - Protozoa involved in butyric rather than lactic fermentative pattern during
      latent acidosis in sheep.
AB  - We used six ruminally cannulated Texel wethers to study the relative role of
      protozoa and lactate-metabolizing bacteria in ruminal fermentative patterns
      during an induced latent acidosis. The sheep were fed an alfalfa hay diet (H) and
      latent acidosis was induced, following a short transition period of one week,
      with a grain-rich acidotic diet (W, 60% wheat + 40% alfalfa hay). Ruminal pH,
      ruminal volatile fatty acids (VFA), lactate and NH3 concentrations, protozoa and
      lactate-utilizing bacterial counts, the relative proportions of three main
      bacteria implicated in lactate metabolism (a lactate-producing species,
      Streptococcus bovis, and two lactate-utilizing species, Selenomonas ruminantium,
      and Megasphaera elsdenii) using specific 16S-rRNA-targeting oligonucleotide
      probes, and lactate dehydrogenase (LDH) activity were determined for both diets.
      The pH parameters (mean, minimum, maximum, time and area under pH 6.0 and 5.5)
      measured with the W diet were indicative of a latent (i.e., subacute and
      maintained) acidosis. However, a butyric rather than lactic latent acidosis was
      observed in this study. Total ruminal lactate concentration remained at low
      levels with the acidotic diet (< 4 mmol x L(-1)), but changes were observed in
      VFA composition, which was oriented towards butyrate at the expense of acetate (P
      < 0.05), while propionate remained constant. In agreement with the low ruminal
      lactate concentration, no changes in the proportion of S. bovis 16S-rRNA were
      observed. The lactate-metabolizing bacterial population also remained fairly
      constant in number, proportion and activity. The increase in butyrate
      concentration was accompanied by a proliferation of entodiniomorphs (P < 0.01).
      These results suggest that the protozoa limited lactate accumulation and possibly
      also the decrease in pH during latent acidosis. Experiments with defaunated and
      faunated sheep could provide further evidence of the role of protozoa in the
      development of rumen latent acidosis.

PMID- 15460160
TI  - Texture of the zona pellucida of the mature pig oocyte. The mammalian egg
      envelope revisited.
AB  - The zona pellucida (ZP) of mature pig oocytes is believed to consist of a dense
      filamentous meshwork, less compact on the inner and outer faces. The uneven
      surface of the ZP is made of unordered and stretched fibrils surrounding deep
      funnels which are the openings of the radial canaliculi. The topography of the ZP
      surface may contribute to the initial interplay between male and female gametes.
      Using cytochemical techniques for transmission electron microscopy (TEM), such as
      tannic acid and ruthenium red treatments, we found that the ZP of pig oocytes was
      essentially made of bundles of fibrils distributed in concentric layers (except
      in the innermost and outer parts). A correlation appears between the dense
      structure of the core layer of the ZP and its texture: it is constituted of
      superposed layers of fibril bundles, whereas only a random meshwork is found in a
      very thin innermost and in the outer layer. The fascicular configuration may
      control the permeability of the ZP, giving its semi-rigidity and elasticity, and
      may facilitate sperm penetration. The liquid crystal-like design of the core
      layer of the ZP is similar to textures found in the the vitelline envelope (zona
      radiata) of other vertebrates and possibly of all the deuterostomes. Such texture
      is probably related to the unique ZP protein composition and to a coordinated
      synthesis.

PMID- 15460161
TI  - Optimisation of in vitro culture conditions in B6CBF1 mouse embryos.
AB  - This study was undertaken to investigate the effects of three media, volume and
      type of oil and frequency of observation on the in vitro development of mouse
      zygotes. B6CBF1 female mice (4 to 6 wk old) were superovulated using PMSG/hCG and
      mated with a proven fertile male of the same strain. Putative zygotes with polar
      bodies were collected from the oviducts of mated mice, 25-28 h after hCG
      injection, and were cultured in vitro. Embryo development was evaluated at either
      96 h and 120 h or every 24 h for 120 h. The results obtained showed that the CZB
      medium was better than the KSOM and HCO3HTF media, and the use of 1 mL of
      paraffin oil was better than the use of 0.5 mL of paraffin oil. The effect of
      paraffin oil and mineral oil on embryo development was examined and the results
      indicated that the use of paraffin oil was better than the use of mineral oil.
      Repeated observations did not influence the proportion of embryos developing to
      blastocysts.

PMID- 15460162
TI  - Response of hexokinase enzymes and the insulin system to dietary carbohydrates in
      the common carp, Cyprinus carpio.
AB  - The response of the common carp to diets with varying amounts of digestible
      starch, provided either as pea meal (LP, HP, 30 and 46% peas, respectively) or as
      cereal (LW, HW, 30 and 46% wheat, respectively), was studied and compared with
      the response to a carbohydrate-free protein-rich diet (CF). Here we focused on
      the utilisation of dietary carbohydrates by examining the relationship between
      dietary starch intake, hepatic hexokinase activities, circulating insulin and
      muscle insulin receptor system. Plasma glucose concentration and hepatic high Km
      hexokinase (glucokinase, GK) activity were not affected by the content of
      digestible starch, but 6 h after feeding enzyme activity was higher in the fish
      fed carbohydrate diets. Similarly, low Km hexokinase (HK) activity was also
      higher in the fish 24 h after feeding. Fat gain and protein retention were
      significantly improved by increased digestible starch intake, especially in the
      HP group, which in turn, presented the highest plasma insulin levels. Glycogen
      stores were moderately increased by the ingestion of digestible starch. The
      number of insulin receptors was greater in the CF group than in fish on
      carbohydrates, except the HP group. Our results confirmed that the common carp
      uses dietary carbohydrates efficiently, especially when there are provided by
      peas. This efficiency might be related to the enhanced response of postprandial
      insulin observed in the HP group.

PMID- 15460163
TI  - Effect of frozen semen on the uterus of mares with pathological uterine changes.
AB  - Pregnancy rates after frozen semen inseminations (AI), particularly in older and
      problem mares, are lower than after fresh semen AI. Uterine contractility and the
      inflammatory reaction after frozen semen insemination were studied in two groups
      of mares: the abnormal group comprised of 6 old barren mares categorized in
      biopsy category IIB or III, and the control group including 6 reproductively
      normal young maiden mares in biopsy category I or IIA. All 12 mares were
      inseminated in the first cycle with 2 mL of phosphate-buffered saline (PBS) and
      in their second cycle with 2 mL of frozen semen containing 800 x 10(6)
      spermatozoa. Before and 1, 2, 4, 8, and 20 to 24 h after this treatment, all
      mares were examined by ultrasonography for intrauterine fluid accumulations
      (IUFA). The examinations were videotaped to count the number of uterine
      contractions later. Uterine fluid was obtained by tampon before treatment, and by
      the tampon method followed by uterine lavage after the last examination. Fluids
      were cultured bacteriologically, and polymorphonuclear leukocytes (PMN) were
      counted. Trypsin-inhibitor capacity (TIC), lysozyme concentration, and beta
      glucuronidase (BGase) and N-acetyl-beta-D-glucosaminidase (NAGase) activities
      were determined in frozen-thawed tampon and lavage fluids. Both treatments
      induced significant neutrophilia in the uterine lumen. Although PMN
      concentrations were numerically higher after frozen semen AI than after PBS
      treatment, the difference was not significant. There was not any difference
      between the mare groups either. The amount of IUFA differed only in the normal
      group between frozen semen AI and PBS treatment, and between 0- and 24-h samples
      for frozen semen AI. Although abnormal mares showed consistently more fluid than
      normal mares, this difference was not significant. Uterine contractions and
      enzyme concentrations between groups did not differ. None of the variables showed
      significant differences between the normal and abnormal mares in their reaction
      to frozen semen AI.

PMID- 15460164
TI  - Prepartum peripherally-induced hyposmia does not reduce postpartum anoestrus
      duration in nursing goats.
AB  - Parturient goats rapidly develop exclusive nursing of their own litter that
      relies on olfactory recognition of the young. They also show a period of
      postpartum anoestrus whose duration depends on the presence of the kid. In
      cattle, maternal selectivity is one of the factors that delays the recovery of
      sexual activity. To investigate the possible influence of maternal selectivity on
      the duration of postpartum anoestrus in goats, we compared the recovery of estrus
      behavior by daily estrus detection with an active buck in intact and selective
      nursing goats (n = 24) with that of dams rendered non-selective by peripheral
      hyposmia with ZnSO4 (n = 18). Postpartum anoestrus duration was shorter in intact
      (68+/-7 days) than in hyposmic mothers (93+/-7 days; P < 0.05). However, the
      cycles of normal duration were less frequent in intact goats (P = 0.03). We
      conclude that in nursing goats, preventing the establishment of selective nursing
      by prepartum peripheral hyposmia does not reduce postpartum anoestrus duration.
      Our results suggest that daily exposure to the buck may result in an earlier
      recovery of ovarian activity in intact mothers.

PMID- 15460165
TI  - Analysis of the 2nd symposium "Anomalies of fatty acids, ageing and degenerating
      pathologies".
AB  - The second symposium on anomalies of fatty acids, ageing and degenerating
      pathologies for the French-speaking community was held during January 2002 in
      Paris (France) and reunited more than 200 participants, including a majority of
      medical practitioners. It was organised around 8 conferences treating the
      following subjects: a general presentation of the metabolism of fatty acids and
      their biological functions (in particular polyunsaturated fatty acids or PUFA),
      the exploration of PUFA in man during situations of nutritional and pathological
      disequilibrium, and the importance of PUFA in the aetiology and prevention of
      pathophysiologies such as cardiovascular, autoimmune and inflammatory diseases,
      diabetes and obesity, cancer and certain neuropsychiatric affections such as
      depression. Indeed, even though edible fatty acids present a common energetic
      function, by beta-oxidation, and a structural function, as a constituent of
      membrane lipids, some of them have a more specific role as an essential nutrient.
      These are essential fatty acids including the two families of polyunsaturated
      fatty acids (n-6 and n-3 PUFA). Their metabolism leads to the synthesis of
      derivatives found in cellular membranes (structural role) and oxygenated
      molecules, the eicosanoids, whose main action is of the same type as that of
      hormones. These derivatives and oxygenated molecules also regulate different
      metabolic pathways by modulating the expression of target genes via activation of
      specific transcription factors. Due to their quality and their quantity in food,
      the PUFA may interfere with the incidence of a large number of pathologies whose
      causes are varied (cardiovascular and inflammatory diseases, cancers,
      neuropathologies, ...). The particular interest in nutrition of PUFA of the n-3
      series (or omega3) and in particular of long-chain derivatives mainly found in
      high quantity in fish oils (eicosapentaenoic acid and docosahexaenoic acid) is
      now widely confirmed for cardiovascular and inflammatory physiology and formed
      the subject of increasing investigations for prevention of certain pathologies of
      the central nervous system. In this paper, we are first going to recall the
      generalities of metabolism and functional properties of PUFA. Secondly, we will
      list the pathologies whose frequency and symptoms are susceptible to be corrected
      by the dietary intake of PUFA, notably by reaching the nutritional equilibrium
      between the family of linoleic acid (n-6 or omega6) and that of alpha-linolenic
      acid (n-3 or omega3).

PMID- 15460166
TI  - Alteration of polyunsaturated fatty acid status and metabolism in health and
      disease.
AB  - Essential polyunsaturated fatty acids (PUFA) cannot be synthesised in the body
      and must be ingested by food. A balanced intake of both n-6 and n-3 PUFA is
      essential for good health. PUFA are the basic constituents of phospholipid
      membranes and determine cellular membrane fluidity and modulate enzyme
      activities, carriers and membrane receptors. They are also precursors of active
      metabolites known collectively as eicosanoids (prostaglandins, prostacyclins,
      thromboxanes and leukotrienes) which regulate our cellular functions. Studies
      indicate that n-3 PUFA have anti-inflammatory, antithrombotic, antiarrhythmic
      actions and immuno-modulating properties. Erythrocyte fatty acid status is a
      reflection of dietary fat intake. It also explores PUFA metabolism and gives
      information about the integration of these fatty acids into cellular membranes.
      Thus, erythrocyte fatty acid analysis can detect PUFA insufficiencies and
      imbalances from the diet, but also metabolic abnormalities and lipid
      peroxidation. It can be helpful in the prevention and the control of chronic
      diseases in which PUFA alterations have been observed as coronary heart diseases,
      hypertension, cancer, diabetes, inflammatory and auto-immune disorders, atopic
      eczema, Alzheimer dementia, major depression, schizophrenia, multiple sclerosis,
      etc.

PMID- 15460167
TI  - Use and misuse of dietary fatty acids for the prevention and treatment of
      coronary heart disease.
AB  - In the recent years, the health effects of fish (and n-3 fatty acids) have
      attracted considerable scientific interest. The present consensus is that the
      cardioprotection of very long chain n-3 fatty acids (also called EPA and DHA) at
      the low dosage used in recent secondary prevention trials primarily results from
      an effect on the ischemic myocardium and probably not from an effect on blood
      lipids and hemostasis. In other words, at these low dosages, there is apparently
      no major effect of these fatty acids on the progression of the vascular
      atherosclerotic lesions. In contrast, dietary alpha-linolenic acid (ALA), the
      parent compound of the very long chain n-3 fatty acids occurring in some
      vegetable oils, may be protective through mechanisms other than the myocardial
      (anti-arrhythmic) ones. In addition to its own direct preventive effect on
      cardiac arrhythmias, dietary ALA actually inhibits the elongation and
      desaturation of linoleic acid (18:2 n-6) into arachidonic acid. Because
      arachidonic acid (20:4 n-6) plays an important role in inflammation (as the
      precursor of the proinflammatory eicosanoids and leukotrienes), modifying its
      amount in blood and cell membranes influences the prevalence and severity of
      eicosanoid-related disorders, including atherosclerotic complications. The
      present knowledge of n-3 fatty acids justifies that physicians, in particular
      cardiologists in the context of secondary prevention of coronary heart disease,
      manage their patients, the young and the old, to increase their consumption of
      these fatty acids. They can only advise them to adequately adapt their diet (for
      instance in primary prevention), but in most cases, the systematic prescription
      of capsules containing oils enriched in ALA and EPA + DHA will be, ethically and
      scientifically, an obligation.

PMID- 15460168
TI  - N-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin
      resistance associated to type 2 diabetes and obesity?
AB  - n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA), mainly eicosapentaenoic
      acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3), are present in
      mammal tissues both from endogenous synthesis from desaturation and elongation of
      18:3 n-3 and/or from dietary origin (marine products and fish oils). In rodents
      in vivo, n-3 LC-PUFA have a protective effect against high fat diet induced
      insulin resistance. Such an effect is explained at the molecular level by the
      prevention of many alterations of insulin signaling induced by a high fat diet.
      Indeed, the protective effect of n-3 LC-PUFA results from the following: (a) the
      prevention of the decrease of phosphatidyl inositol 3' kinase (PI3 kinase)
      activity and of the depletion of the glucose transporter protein GLUT4 in the
      muscle; (b) the prevention of the decreased expression of GLUT4 in adipose
      tissue. In addition, n-3 LC-PUFA inhibit both the activity and expression of
      liver glucose-6-phosphatase which could explain the protective effect with
      respect to the excessive hepatic glucose output induced by a high fat diet. n-3
      LC-PUFA also decrease muscle intramyofibrillar triglycerides and liver steatosis.
      This last effect results on the one hand, from a decreased expression of
      lipogenesis enzymes and of delta 9 desaturase (via a depleting effect on sterol
      response element binding protein 1c (SREBP-1c). On the other hand, n-3 LC-PUFA
      stimulate fatty acid oxidation in the liver (via the activation of peroxisome
      proliferator activated receptor alpha (PPAR-alpha)). In patients with type 2
      diabetes, fish oil dietary supplementation fails to reverse insulin resistance
      for unclear reasons, but systematically decreases plasma triglycerides.
      Conversely, in healthy humans, fish oil has many physiological effects. Indeed,
      fish oil reduces insulin response to oral glucose without altering the glycaemic
      response, abolishes extraggression at times of mental stress, decreases the
      activation of sympathetic activity during mental stress and also decreases plasma
      triglycerides. These effects are encouraging in the perspective of prevention of
      insulin resistance but further clinical and basic studies must be designed to
      confirm and complete our knowledge in this field.

PMID- 15460169
TI  - Pharmacovigilance in the 21st century: new systematic tools for an old problem.
AB  - The large number of adverse-event reports generated by marketed drugs and devices
      argues for the application of validated computerized algorithms to supplement
      traditional methods of detecting adverse-event signals. Difficulties in
      accurately estimating patient exposure and background rates for a given event in
      a specific population hinder risk estimation in spontaneous adverse-event
      databases. The United States Food and Drug Administration (FDA) is evaluating a
      Bayesian data mining system called Multi-item Gamma Poisson Shrinker (MGPS) to
      enhance the FDA's ability to monitor the safety of drugs, biologics, and vaccines
      after they have been approved for use. The MGPS computes adjusted higher-than
      expected reporting relationships between drugs and adverse events across 35 years
      of data relative to internal background rates. The MGPS can also adjust for
      random noise by using a model derived from the data, and corrects for temporal
      trends and confounding related to age, sex, and other variables by stratifying
      over 900 categories. Signals can then be compared with or used in conjunction
      with other sources (e.g. clinical trials, general practice databases) to further
      study the adverse-event risk. The example of pancreatitis risk with atypical
      antipsychotics, valproic acid, and valproate is used to discuss the strengths and
      limitations of MGPS versus traditional methods. Validated data mining techniques
      offer great promise to enhance pharmacovigilance practices.

PMID- 15460170
TI  - Pharmacoepidemiology II: the nested case-control study--a novel approach in
      pharmacoepidemiologic research.
AB  - This article on pharmacoepidemiology, the second of two parts, is a more focused
      discussion of the methodology of cohort studies and case-control studies, the
      basic methodologies of which were discussed in part I. The nested case-control
      study incorporates the strengths of both the cohort and case-control studies but
      may alleviate some of the methodologic challenges inherent in both types of
      studies. In a nested case-control study, a cohort of individuals is followed
      during certain time periods until a certain outcome is reached. The analysis is
      conducted as a case-control study in which cases are matched to only a sample of
      control subjects. Matching allows for control of potential confounding variables
      such as age, calendar time, and disease duration. Also, the time dependency of an
      exposure can be quantified without complicated statistical techniques. Matching
      the cases and controls by time allows the investigator to stratify exposure based
      on current, past, or intermittent use. By using the principles of epidemiology,
      the nested case-control study allows for the control of confounding variables, as
      well as better quantification of time-dependent exposures.

PMID- 15460171
TI  - Pharmacokinetics and pharmacodynamics of methadone enantiomers after
      coadministration with amprenavir in opioid-dependent subjects.
AB  - STUDY OBJECTIVE: To investigate the steady-state pharmacokinetics of methadone
      enantiomers when coadministered with amprenavir. DESIGN: Prospective, open-label,
      within-subject pharmacokinetic study. SETTING: University research center.
      SUBJECTS: Nineteen opioid-dependent, methadone-maintained, healthy individuals
      were enrolled. INTERVENTION: On study day 1, subjects received their usual once
      daily dose of methadone alone. On study days 2-11, they received the same once
      daily methadone dose plus amprenavir 1200 mg twice/day. Serial blood samples were
      collected over 24 hours on study days 1 and 11 for measurement of plasma R- and S
      methadone, and over 12 hours on day 11 for serum amprenavir concentrations.
      MEASUREMENTS AND MAIN RESULTS: Standard pharmacokinetic parameters were
      determined from the concentrations and compared between the two treatments
      (methadone alone vs methadone with amprenavir). Subjects served as their own
      control for methadone comparisons, and amprenavir comparisons were made by using
      a historic control group (38 healthy men). Opioid-effect measures were assessed
      throughout the study. Coadministration of amprenavir with methadone resulted in a
      3-4-hour delay in plasma R- and S-methadone enantiomer peak concentrations at
      steady state (Cmax-ss). The active R-methadone enantiomer area under the plasma
      concentration-time curve during a dosing interval (AUCt-ss, Cmax-ss, and the
      minimum plasma concentration at steady state (Cmin-ss) were decreased by 13%,
      25%, and 21%, respectively, after coadministration of methadone and amprenavir.
      The inactive S-enantiomer AUCt-ss, Cmax-ss, and Cmin-ss were decreased by 40%,
      48%, and 52%, respectively. No clinically significant changes were noted in
      opioid pharmacodynamic effects, and there was no evidence of opioid withdrawal.
      No methadone dosage was changed in any subject. CONCLUSION: No a priori
      adjustment in methadone dosage is required during coadministration with
      amprenavir as there is only a small effect on R-methadone exposure and no
      evidence of opioid withdrawal.

PMID- 15460172
TI  - Application of an empiric Bayesian data mining algorithm to reports of
      pancreatitis associated with atypical antipsychotics.
AB  - STUDY OBJECTIVE: To compare the results from one frequently cited data mining
      algorithm with those from a study, which was published in a peer-reviewed
      journal, that examined the association of pancreatitis with selected atypical
      antipsychotics observed by traditional rule-based methods of signal detection.
      DESIGN: Retrospective pharmacovigilance study. INTERVENTION: The widely studied
      data mining algorithm known as the Multi-item Gamma Poisson Shrinker (MGPS) was
      applied to adverse-event reports from the United States Food and Drug
      Administration's Adverse Event Reporting System database through the first
      quarter of 2003 for clozapine, olanzapine, and risperidone to determine if a
      significant signal of pancreatitis would have been generated by this method in
      advance of their review or the addition of these events to the respective product
      labels. MEASUREMENTS AND MAIN RESULTS: Data mining was performed by using nine
      preferred terms relevant to drug-induced pancreatitis from the Medical Dictionary
      for Regulatory Activities (MedDRA). Results from a previous study on the
      antipsychotics were reviewed and analyzed. Physicians' Desk References (PDRs)
      starting from 1994 were manually reviewed to determine the first year that
      pancreatitis was listed as an adverse event in the product label for each
      antipsychotic. This information was used as a surrogate marker of the timing of
      initial signal detection by traditional criteria. Pancreatitis was listed as an
      adverse event in a PDR for all three atypical antipsychotics. Despite the
      presence of up to 88 reports/drug-event combination in the Food and Drug
      Administration's Adverse Event Reporting System database, the MGPS failed to
      generate a signal of disproportional reporting of pancreatitis associated with
      the three antipsychotics despite the signaling of these drug-event combinations
      by traditional rule-based methods, as reflected in product labeling and/or the
      literature. These discordant findings illustrate key principles in the
      application of data mining algorithms to drug safety surveillance. CONCLUSION:
      The optimal place of data mining algorithms in the pharmacovigilance tool kit
      remains to be determined, requires consideration of numerous factors that may
      affect their performance, and is highly situation dependent.

PMID- 15460173
TI  - Evaluation of gastric pH and guaiac measurements in neonates receiving acid
      suppression therapy during extracorporeal membrane oxygenation.
AB  - STUDY OBJECTIVES: To assess gastric pH measurements, evaluate the frequency of
      guaiac-positive gastric aspirates, and characterize the appearance of gastric
      aspirates in neonates receiving acid suppression therapy during extracorporeal
      membrane oxygenation (ECMO). DESIGN: Retrospective, observational study. SETTING:
      Intensive care unit in a 225-bed tertiary care pediatric referral hospital.
      SUBJECTS: Thirteen neonates receiving ECMO. MEASUREMENTS AND MAIN RESULTS:
      Gastric pH measurements, guaiac test results, appearance of gastric aspirates,
      and ranitidine and antacid dosing were recorded. On ECMO day 1, mean+/-SD gastric
      pH was 4.3+/-2.8 in the five neonates whose pH was documented. Intravenous
      ranitidine 2.9+/-0.4 mg/kg/day was started in all neonates by ECMO day 2. Gastric
      pH was less than 4.0 in seven neonates; these low pH values accounted for only
      10% of gastric pH measurements. The frequency of positive guaiac results in
      neonates with pH measurements below 4.0 was 27% compared with 41% for neonates
      with a gastric pH of 4.0 or greater (p=0.125). Guaiac tests were positive in 69
      (42%) aspirates in 11 neonates. Of the guaiac-positive aspirates that had a
      corresponding pH measurement, 94% had a pH of 4.0 or greater. Guaiac-positive
      aspirates had evidence of bile (49%), antacid (17%), and blood (7%) in gastric
      fluid. In six patients, ranitidine dosages were increased to 3.9+/-0.6 mg/kg/day
      due to low pH and/or positive guaiac results. In two of these neonates, gastric
      pH remained below 4.0 in nine of 35 pH measurements despite increased ranitidine
      dosing. Guaiac results remained positive in all subsequent aspirates in five out
      of six of these neonates. No neonates developed clinically significant upper
      gastrointestinal bleeding (UGIB). CONCLUSIONS: Gastric pH is variable in neonates
      receiving histamine2-receptor antagonist and antacid therapy during ECMO, and
      gastric pH of 4.0 or greater does not decrease the frequency of guaiac-positive
      aspirates. Higher gastric pH measurements are confounded by duodenogastric reflux
      and the presence of blood and/or antacid in gastric fluid. Motility agents in
      combination with acid suppression therapy for prevention of UGIB may be necessary
      in this setting based on gastric pH measurements, appearance of gastric
      aspirates, and guaiac testing.

PMID- 15460174
TI  - Impact of nesiritide on health care resource utilization and complications in
      patients with decompensated heart failure.
AB  - STUDY OBJECTIVE: To determine the impact of nesiritide on health care resource
      utilization and complications in patients hospitalized with decompensated heart
      failure. DESIGN: Retrospective case-control study. SETTING: United States
      hospitals. PATIENTS: Two hundred sixteen patients hospitalized for decompensated
      heart failure. MEASUREMENTS AND MAIN RESULTS: One hundred eight patients who
      received a nesiritide infusion for a minimum of 12 hours during the first 48
      hours after hospital admission were matched with 108 patients not receiving
      nesiritide. Health care resource utilization, consisting of hospital length of
      stay (LOS), rate of rehospitalization within 90 days, concomitant drugs
      administered, and laboratory and diagnostic tests, was determined for each
      hospital admission. Rates of adverse events also were recorded. Patients
      receiving nesiritide had a significantly shorter LOS in a critical care unit
      (p=0.03). General medical ward or step-down unit LOS was not different between
      the treatment groups. A favorable trend toward a lower rate of rehospitalization
      over the 90-day follow-up period was observed with nesiritide (p=0.07). The
      number of patients who developed life-threatening ventricular arrhythmias and
      hypotension was similar for both treatment groups. However, in patients receiving
      nesiritide, significantly less atrial fibrillation (p=0.03) and renal dysfunction
      (p=0.04) occurred compared with patients not receiving nesiritide. CONCLUSION:
      Nesiritide therapy is associated with significant reductions in both health care
      resource utilization and complications in patients with decompensated heart
      failure.

PMID- 15460175
TI  - Extended-release divalproex sodium for mood stabilization.
AB  - STUDY OBJECTIVE: To evaluate the efficacy, safety, and tolerability of extended
      release divalproex sodium. DESIGN: Prospective, open-label, 4-week study SETTING:
      Long-term care facility of the Missouri Department of Mental Health. PATIENTS:
      Ten hospitalized patients (mean age 39.4 yrs) with mood or thought disorders who
      were experiencing adverse effects from delayed-release divalproex sodium.
      INTERVENTION: All participants were switched from delayed-release to extended
      release divalproex sodium. MEASUREMENTS AND MAIN RESULTS: Efficacy was monitored
      with the Brief Psychiatric Rating Scale (BPRS), and safety and tolerability were
      monitored with the Systematic Assessment for Treatment Emergent Events (SAFTEE).
      Frequently reported adverse effects before conversion were sedation, stomach
      upset, and tremor. At study conclusion, no differences were seen in total BPRS
      scores or individual BPRS items, although a trend pointed to decreased somatic
      complaints (p=0.057). The mean serum concentration of valproic acid among
      participants did not change significantly in the transition from the delayed
      release formulation to an equivalent dose-adjusted extended-release formulation
      (90.5 mg/L vs 95.5 mg/L, p=0.493). At study conclusion, significant decreases in
      low-density lipoprotein cholesterol (p=0.010) and potassium (p=0.043) levels were
      identified. Three categories of adverse effects decreased significantly after
      patients switched to the extended-release form of divalproex sodium: sedation
      (p=0.022), stomach or abdominal discomfort (p=0.045), and tremor (p=0.004).
      CONCLUSION: This preliminary investigation suggests that patients receiving
      delayed-release divalproex sodium for mood lability can be converted successfully
      to extended-release divalproex sodium. Moreover, these findings imply that this
      transition is associated with a reduction in some of the adverse effects
      associated with divalproex sodium.

PMID- 15460176
TI  - Potential in vitro interaction between tenecteplase and unfractionated heparin.
AB  - STUDY OBJECTIVE: To explore the potential of a direct drug interaction between
      unfractionated heparin (UFH) and tenecteplase that lowers the pharmacologic
      propensity of UFH to prolong the activated partial thromboplastin time (aPTT).
      DESIGN: In vitro experiment. SETTING: Texas Tech University School of Pharmacy,
      with sample analysis performed at an independent, contract laboratory. Samples.
      Blood samples collected from healthy volunteers. INTERVENTION: Three separate in
      vitro experiments were conducted to explore the relative influence of various
      thrombolytic agents with and without UFH on aPTT prolongation. In each
      experiment, blood from healthy volunteers (12 for each experiment) was treated
      with different concentrations and combinations of tenecteplase and UFH.
      MEASUREMENTS AND MAIN RESULTS: When the effects of tenecteplase plus UFH versus
      UFH alone on aPTT prolongation were compared, each experiment demonstrated
      attenuation of aPTT with the combination versus UFH alone. In contrast, findings
      for other thrombolytic agents combined with UFH demonstrate elevation of the aPTT
      compared with UFH alone. CONCLUSION: The results indicate a possible drug
      interaction between tenecteplase and UFH, with tenecteplase attenuating the
      intensity of anticoagulation of UFH in vitro. Further investigation into this
      possible interaction is warranted in the clinical setting.

PMID- 15460177
TI  - Current and future immunosuppressive strategies in renal transplantation.
AB  - The past decade has witnessed the introduction of several new immunosuppressive
      agents. The availability of these new pharmacologic offerings has not diminished
      the challenge of achieving a balance of adequate graft protection while
      minimizing the consequences of excessive immunosuppression. For renal transplant
      recipients, maintenance immunosuppression generally consists of a calcineurin
      inhibitor in combination with an antiproliferative agent and a corticosteroid;
      more recently, mammalian target of rapamycin inhibitors have been used. Excellent
      results have been achieved at many transplant centers with combinations of these
      agents in a variety of protocols. Regimens designed to limit or eliminate
      calcineurin inhibitor and/or corticosteroid therapy are actively being pursued in
      the transplant community. Allograft tolerance and xenotransplantation are being
      studied, and the knowledge gained from the effort may help in the development of
      innovative strategies and new immunosuppressive agents.

PMID- 15460178
TI  - Paradoxical reactions to benzodiazepines: literature review and treatment
      options.
AB  - Benzodiazepines frequently are administered to patients to induce sedation.
      Paradoxical reactions to benzodiazepines, characterized by increased
      talkativeness, emotional release, excitement, and excessive movement, are
      relatively uncommon and occur in less than 1% of patients. The exact mechanism of
      paradoxical reactions remains unclear. Most cases are idiosyncratic; however,
      some evidence suggests that these reactions may occur secondary to a genetic
      link, history of alcohol abuse, or psychological disturbances. This review
      evaluates the numerous cases of paradoxical reactions to benzodiazepines in adult
      and pediatric patients that have been reported in the biomedical literature. It
      also explores the advantages and disadvantages of the various available treatment
      options.

PMID- 15460179
TI  - Role of topiramate for the treatment of painful diabetic peripheral neuropathy.
AB  - OBJECTIVE: To review the possible role of topiramate for the treatment of
      neuropathic pain and, specifically, the pain of diabetic peripheral neuropathy.
      DATA SOURCES: Clinical studies and abstracts were identified by using PubMed
      (January 1966--October 2003), Ovid (January 1966--December 2003), and
      International Pharmaceutical Abstracts (January 1970--December 2003) and by
      reviewing bibliographies of published studies. Key search terms included pain,
      peripheral neuropathy, diabetes, and topiramate. English-language studies were
      identified, as were pertinent references from these articles. DATA SYNTHESIS:
      Published data are limited on the successful use of topiramate in the treatment
      of neuropathic pain syndromes, and only three prospective studies evaluated the
      effectiveness of topiramate in diabetic peripheral neuropathy. In addition, the
      use of topiramate to treat diabetic neuropathic pain syndromes successfully may
      be limited by patients' inability to tolerate the adverse effects associated with
      the agent. CONCLUSIONS: Topiramate has been used successfully in relieving the
      pain of various neuropathies, including painful diabetic peripheral neuropathy.
      Randomized controlled trials that specifically focus on the use of topiramate in
      patients with painful diabetic peripheral neuropathy are needed to confirm the
      initial findings in case reports, abstracts, and small clinical trials that have
      focused on treating numerous neuropathic pain syndromes, including diabetic
      peripheral neuropathy.

PMID- 15460180
TI  - Statin-associated peripheral neuropathy: review of the literature.
AB  - Various pharmacologic agents are available for the treatment of
      hypercholesterolemia, including 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors, commonly referred to as statins, which offer favorable
      lipid-lowering effects and reductions in morbidity and mortality. Statins are
      usually better tolerated than other lipid-lowering agents and therefore have
      become a mainstay of treatment for hypercholesterolemia. However, recent case
      reports of peripheral neuropathy in patients treated with statins may have gone
      unnoticed by health care professionals. To evaluate the possible link between
      statins and peripheral neuropathy, literature searches using MEDLINE (January
      1993--November 2003) and International Pharmaceutical Abstracts (January 1970-
      June 2002) were performed. Key search terms were statin, neuropathy, and HMG-CoA
      reductase inhibitors. Based on epidemiologic studies as well as case reports, a
      risk of peripheral neuropathy associated with statin use may exist; however, the
      risk appears to be minimal. On the other hand, the benefits of statins are firmly
      established. These findings should alert prescribers to a potential risk of
      peripheral neuropathy in patients receiving any of the statins; that is, statins
      should be considered the cause of peripheral neuropathy when other etiologies
      have been excluded.

PMID- 15460181
TI  - Impact of oral direct thrombin inhibitors on anticoagulation clinics.
AB  - OBJECTIVES: To characterize the services and activities performed by
      anticoagulation clinics (ACCs) across the United States, examine the anticipated
      impact that oral direct thrombin inhibitors (DTIs) will have on the clinical
      services of ACCs, and elicit possible management strategies to realign services
      provided by ACCs and opportunities for restructuring clinical services. METHODS:
      A survey was developed in consultation with content experts in the field,
      pretested by several ACC providers, and subsequently refined. Surveys were mailed
      to 400 randomly selected ACC-based providers. RESULTS: The final usable response
      rate was 34.5% (115 of 333 surveys). Respondents anticipated that the number of
      patient visits/month would decrease from a median of 336 (interquartile range
      [IQR] 151-775) to 150 (IQR 71-350, p<0.001) after the introduction of oral DTIs.
      In addition, time spent on many direct and indirect patient care activities
      currently performed by ACCs was expected to decline. Respondents indicated that
      ACCs may find new roles by providing guidance on individual suitability for
      therapy, managing the transition to oral DTIs, providing education for patients
      and health care providers on thrombotic disease state management, monitoring
      patients for recurrent thrombosis and risk of bleeding complications, monitoring
      patient compliance, and providing counseling and safety surveillance for patients
      receiving treatment with oral DTIs. CONCLUSION: The advent of oral DTIs is likely
      to have a significant impact on the structure and delivery of antithrombotic
      services. Clinics that are proactive and redesign their patient care services to
      consider emerging anticoagulant agents will be more likely to remain relevant and
      viable.

PMID- 15460182
TI  - Impaired warfarin response secondary to high-dose vitamin K1 for rapid
      anticoagulation reversal: case series and literature review.
AB  - The literature suggests that unresponsiveness to warfarin can continue for 1 week
      or longer after administration of high-dose vitamin K1 10 mg or greater; however,
      there is a lack of supporting data to define the duration and clinical
      consequences of impaired warfarin response with high doses of vitamin K1. This
      case series describes four patients receiving indefinite warfarin therapy who
      received high and, in most cases, repeated doses of vitamin K1 for urgent
      reversal of therapeutic anticoagulation for an invasive procedure or surgery. The
      patients displayed impaired warfarin response for 11 days-3.5 weeks after
      administration of vitamin K1 10-40 mg. The associated financial burden for the
      patients was substantial. We reviewed the literature to examine the mechanism of
      impaired warfarin response, and the clinical efficacy, safety, and
      appropriateness of vitamin K1 and fresh-frozen plasma in urgent reversal of
      anticoagulation.

PMID- 15460183
TI  - Acute pulmonary edema caused by quinine.
AB  - A 57-year-old man who had been intermittently taking one 300-mg tablet of quinine
      sulfate orally for leg cramps experienced transient acute pulmonary edema and
      hypotension 30-40 minutes after ingestion on two consecutive occasions. He was
      not taking any concomitant drugs, and there was no alternative explanation for
      either event. Serial troponin T tests and electrocardiograms, obtained on
      admission to the hospital, followed by an outpatient echocardiogram and a
      coronary angiogram, were essentially normal. We compared this case with one
      previously published and nine previously unpublished reports of quinine
      associated pulmonary edema and conclude that some cases of pulmonary edema or
      adult respiratory distress syndrome in patients with malaria may be caused by an
      adverse reaction to quinine. Although infrequent, clinicians should be aware of
      this potentially serious and costly adverse reaction.

PMID- 15460184
TI  - Enterococcus faecalis resistant to linezolid: case series and review of the
      literature.
AB  - Reports of linezolid resistance among Enterococcus faecalis have been relatively
      rare. We describe three patients with linezolid-resistant strains of E. faecalis,
      discovered after the patients had received long courses (> 30 days) of linezolid
      therapy. All strains contained the G2576U mutation in 23S rRNA. A literature
      review revealed one other case in the United States and three cases in Europe;
      all involved patients who had received long courses of therapy. It appears that
      recent or extended linezolid therapy may be a risk factor for development of
      resistant E. faecalis. In patients who have recently been treated with linezolid
      and have an identified new systemic enterococcal isolate, linezolid sensitivity
      should be verified as soon as possible to guide therapy. This strategy also
      should be considered for patients with a breakthrough enterococcal isolate during
      linezolid therapy.

PMID- 15460185
TI  - Biliary excretion of imatinib mesylate and its metabolite CGP 74588 in humans.
AB  - Imatinib mesylate, licensed to treat chronic myelogenous leukemia and
      gastrointestinal stromal tumors, is metabolized by cytochrome P450 3A and
      undergoes little renal excretion, but its biliary excretion by humans is
      uncharacterized. Liquid chromatography-mass spectrometry was used to quantitate
      imatinib and its metabolite CGP 74588 in the bile of two patients with biliary
      stents; the ratio of imatinib:CGP 74588 in each was approximately 9:1. In the
      first patient, who was receiving long-term therapy with imatinib 400 mg/day and
      had normal liver function tests, biliary imatinib accounted for 17.7% of the
      daily dose and CGP 74588 accounted for 2.1%. In the second patient, who had
      elevated liver function tests and was studied after his first dose of imatinib
      300 mg, biliary imatinib accounted for only 1.8% of the daily dose and CGP 74588
      accounted for 0.2%. These data show both the qualitative similarities and the
      quantitative variability in biliary excretion of imatinib and its principal
      metabolite.

PMID- 15460186
TI  - Nesiritide for treatment of heart failure due to right ventricular dysfunction.
AB  - Little information exists regarding the use of nesiritide for treatment of right
      sided heart failure. Similarly, little information is available regarding routine
      use of combination nesiritide and diuretics as initial therapy to relieve edema
      due to heart failure. Nesiritide may be beneficial in combination with diuretics
      because it reduces activity of the renin-angiotensin-aldosterone system. It is
      unclear how potent nesiritide is as a diuretic. Patients exhibit wide variability
      in clinical response from the diuretic effects of the drug. Two patients were
      given a combination of nesiritide and diuretics as initial treatment of right
      sided heart failure; both experienced significant diuresis and weight loss.
      Further literature is needed to clarify the role of nesiritide in the treatment
      of right-sided heart failure.

PMID- 15460187
TI  - Healthy People 2010: challenges, opportunities, and a call to action for
      America's pharmacists.

PMID- 15460188
TI  - Antibiotic resistance patterns of group B streptococcal clinical isolates.
AB  - OBJECTIVES: To determine the in vitro resistance of group B streptococcus (GBS)
      to 12 antibiotics. To determine if there has been any decrease in sensitivity to
      the penicillins or other antibiotics currently used for GBS chemoprophylaxis in
      pregnant women. Find suitable alternative antibiotics to penicillin. Find an
      antibiotic that will have minimal selective pressure for resistance among the
      endogenous resident vaginal microflora. METHODS: The antibiotic susceptibility
      profiles of 52 clinical isolates of GBS were evaluated to 12 antibiotics:
      ampicillin, azithromycin, cefamandole, cefazolin, ceftriaxone, ciprofloxacin,
      clindamycin, erythromycin, nitrofurantoin, ofloxacin, penicillin and vancomycin.
      Antibiotic sensitivities were determined using disk diffusion and microdilution
      methods according to the guidelines of the National Committee for Clinical
      Laboratory Standards (NCCLS). RESULTS: All isolates were sensitive to vancomycin,
      ofloxacin, ampicillin, ciprofloxacin, nitrofurantoin and penicillin. However, the
      following number of clinical isolates exhibited intermediate or decreased
      sensitivity, nine (17%) to ampicillin, eight (15%) to penicillin, 14 (32%) to
      ciprofloxacin and one (2%) to nitrofurantoin. Thirty-one percent of the isolates
      were resistant to azithromycin and ceftriaxone, 19% to clindamycin, 15% to
      cefazolin and 13% to cefamandole. Eighteen (35%) of the clinical isolates tested
      were resistant to 6 of the 12 antibiotics tested. CONCLUSIONS: The relatively
      high rates of resistance for 6 of the 12 antibiotics tested suggest that for
      women allergic to penicillin and colonized with GBS, antibiotic sensitivities to
      their isolates should be determined. The antibiotic selected for intrapartum
      chemoprophylaxis should be guided by the organism's antibiotic sensitivity
      pattern. Patients with GBS bacteriuria should be treated with nitrofurantoin.

PMID- 15460189
TI  - Hepatitis C virus (HCV): prevalence in a gynecological urgent care clinic
      population.
AB  - OBJECTIVE: To determine the prevalence of hepatitis C virus (HCV) among women
      seeking urgent gynecological care. METHODS: Women were asked to complete a short
      self-assessment screening of HCV risk. Those answering yes to any of the
      screening questions were offered HCV testing and were asked to complete a more
      detailed questionnaire. RESULTS: Among the 125 women who completed the screening
      questionnaire, 80% (100) answered yes to one or more of the screening questions.
      Of the 99 women who underwent testing, six (6.1%) were HCV seropositive; a
      history of injection drug use was the only finding associated with HCV
      seropositivity (R.R 9.7: 95% CI 1.90-49.40). CONCLUSIONS: Women seeking urgent
      outpatient gynecological care, particularly those who are injection drug users,
      are at a substantial risk of HCV infection. A careful risk assessment should be
      completed in order to identify women who should be offered HCV testing.

PMID- 15460190
TI  - Cytolytic vaginosis: misdiagnosed as candidal vaginitis.
AB  - OBJECTIVES: In this study, 210 women with vaginal discharge and other
      symptoms/signs of genital pathology suggestive of vulvovaginal candidiasis (VVC)
      were involved in order to distinguish true WC and cytolytic vaginosis (CV) cases.
      METHODS: Fungal cultures, 10% potassium hydroxide (KOH) and Gram stained
      preparations and pH measurements were performed on the vaginal discharge material
      of each patient. RESULTS: Fifteen patients (7.1%) were diagnosed with cytolytic
      vaginosis according to their clinical and microbiological findings, including
      abundant lactobacilli, fragmented epithelial cells and/or free nuclei due to
      cytolysis, seen in their discharge materials on microscopic examination, but no
      fungal growth. CONCLUSIONS: The results of this study may contribute to the
      reports in the literature indicating the importance of such disorders, which are
      generally misdiagnosed as candidiasis.

PMID- 15460191
TI  - Clinical evaluation of affirm VPIII in the detection and identification of
      Trichomonas vaginalis, Gardnerella vaginalis, and Candida species in
      vaginitis/vaginosis.
AB  - OBJECTIVE: To compare the Affirm VPIII Microbial Identification Test for
      detection and identification of Candida species, Gardnerella vaginalis and
      Trichomonas vaginalis to clinical and microscopic criteria commonly used to
      diagnose vaginitis. METHODS: Women that were symptomatic for vaginitis/vaginosis
      and asymptomatic women being seen for routine obstetric or gynecological care
      were included in this study. Women treated with antibiotics or antifungals within
      one week or women who had douched within 24 hours were excluded. Two vaginal swab
      specimens were simultaneously obtained from each patient, one swab was placed in
      sterile physiological saline for immediate microscopic wet mount examination and
      KOH testing. The other swab was placed in the Affirm collection tube for Affirm
      VPIII testing based on previously demonstrated methods. RESULTS: The Affirm assay
      was significantly more likely to identify Gardnerella and Candida than wet mount.
      190 (45%) were positive for Gardnerella by Affirm compared to 58 (14%) by wet
      mount; 45 (11%) were positive for Candida by Affirm compared to 31 (7%) by wet
      mount; and 30 (7%) were positive for Trichomonas by Affirm compared to 23 (5%) by
      wet mount. Symptomatic women were significantly more likely to be positive by
      Affirm only (23% vs. 10%), wet mount only (3% vs. 2%) or Affirm and wet mount
      (15% vs. 1%). Asymptomatic women were significantly more likely to be negative
      for Affirm and wet mount (43% vs. 5%). CONCLUSIONS: The Affirm VPIII test is a
      more sensitive diagnostic test for detection and identification of symptomatic
      vaginitis/vaginosis than conventional clinical examination and wet mount testing.

PMID- 15460192
TI  - Antenatal diagnosis of intrauterine infection with coxsackievirus B3 associated
      with live birth.
AB  - BACKGROUND: Prior reported cases of stillbirth and neonates infected with
      enteroviruses suggest transplacental infection. We present a case of fetal
      infection with coxsackievirus B3, diagnosed antenatally and resulting in live
      birth. CASE: A pregnant woman presented at 26 weeks with fetal tachycardia and
      non-immune hydrops fetalis. Coxsackievirus B3 was cultured from amniotic fluid.
      Maternal antibody to coxsackievirus B3 was positive at 1:512. At 32 weeks, the
      fetus deteriorated and was delivered. Cord blood antibody to coxsackievirus B3
      was positive at a higher titer. Following neonatal death, brain and placental
      tissues were positive for enterovirus ribonucleic acid by polymerase chain
      reaction. CONCLUSION: Intrauterine infection by enteroviruses should be
      considered in the differential diagnosis of non-immune hydrops fetalis. Antenatal
      diagnosis of coxsackievirus B3 infection is associated with poor outcome.

PMID- 15460193
TI  - Perimenopausal pneumococcal tubo-ovarian abscess--a case report and review.
AB  - BACKGROUND: Genital tract infections in females secondary to Streptococcus
      pneumoniae (pneumococcus) are unusual. Tubo-ovarian abscess resulting from such
      an infection is a rare occurrence and diagnosis is not always easy. This report
      demonstrates the problems of recognizing this condition and summarizes the
      pathomechanism, investigations leading to a diagnosis and the subsequent
      management. CASE: A rare case of a tubo-ovarian abscess caused by pneumococcus,
      occurring in a previously healthy 48-year-old woman, is presented. The tubo
      ovarian abscess may have developed insidiously and probably had an acute
      exacerbation prior to presentation. CONCLUSION: This case is unusual in that
      there were no identifiable initiating events for the source of the pneumococcal
      infection. Early recognition of a tubo-ovarian abscess is important in order to
      prevent the associated morbidity and mortality. This condition has the propensity
      to mimic a neoplasm.

PMID- 15460194
TI  - Visceral leishmaniasis (kala-azar) and pregnancy.
AB  - OBJECTIVE: The aim of the present review was to close the gap in the approach to
      pregnant women with visceral leishmaniasis (kala-azar) by providing up-to-date
      information to obstetricians about physiopathology, epidemiology, vertical
      transmission, drugs and treatment during pregnancy. BACKGROUND: Infection with
      Leishmania chagasi during pregnancy is rare and deserves special attention since
      little information is available regarding the occurrence of visceral
      leishmaniasis during gestational period and the real possibility of vertical
      transmission of this disease. Because specific areas in the world are endemic for
      the disease and considering the continuous growth of the population, cases of
      pregnant women with visceral leishmaniasis are becoming more frequent.
      Unfortunately, textbooks on infectious diseases do not include this specific
      group of patients, and studies in the literature on aspects related to pregnancy
      and visceral leishmaniasis are scarce. CONCLUSIONS: Vertical transmission of
      leishmaniasis is possible and the institution of treatment is imperative in cases
      of pregnant women with kala-azar. Amphotericin B is strongly recommended as the
      first choice drug due to its fewer maternal-fetal adverse effects.

PMID- 15460195
TI  - Patient or visitor, mentally disturbed individuals may pose a safety threat.
AB  - As the hospital point of entry, EDs often are the first place unstable
      individuals can threaten others. Have specific procedures outlined for visitors
      and for mentally unstable patients. Cooperate closely with your security
      department, but always retain clinical control. Periodically review and update
      your procedures, and have staff re-educated annually.

PMID- 15460196
TI  - CT in your ED? Make sure you've got enough space.
AB  - ED managers in small and medium-sized hospitals should think creatively when
      seeking approval for a department computed tomography scan. Safety considerations
      can make a compelling argument. Piggyback your request onto a larger performance
      improvement initiative. You may find a surprisingly supportive ally in the
      radiology department.

PMID- 15460197
TI  - Strategies to boost ED manager's influence.
AB  - Developing new managerial skills can make a world of difference in the hospital
      board room. Being an expert clinician may not be enough to impress upper
      management. Forget changing people's minds; start working on your own abilities.
      You're running a multimillion dollar business, so think like an executive.

PMID- 15460198
TI  - ED touched by angels slashes complaints.
AB  - Volunteers can be much more than go-fers for your ED staff. Volunteers can free
      up staff time while engendering strong relationships with patients and families.
      Select individuals who have significant life experience, so they can empathize
      with worried, fearful individuals. Staff gain another set of eyes to keep a watch
      on patients after they enter the hospital.

PMID- 15460199
TI  - Transfers: you can say no if there's a good reason.

PMID- 15460200
TI  - What is your diagnosis? Male pseudohermaphroditism.

PMID- 15460201
TI  - Angiostrongylus vasorum infection in 23 dogs (1999-2002).
AB  - Angiostrongylosis was diagnosed in 23 dogs presenting to the Queen Mother
      Hospital for Animals between June 1999 and August 2002. The animals' clinical
      records were reviewed retrospectively and certain risk factors were compared with
      a control population of 3407 dogs. Twenty-two of the 23 dogs were from south-east
      England and dogs from Surrey (n=8) were significantly overrepresented. There were
      also significantly more Cavalier King Charles spaniels (n=5) and Staffordshire
      bull terriers (n=5) among the affected dogs than in the control group. The median
      age of affected dogs was 10 months (range five to 90 months). The most common
      presenting signs were cough (65 per cent), dyspnoea (43 per cent), haemorrhagic
      diathesis (35 per cent) and collapse (26 per cent). Four dogs were
      thrombocytopenic and eight had significant prolongations in prothrombin time
      and/or activated partial thromboplastin time. Thoracic radiographs were abnormal
      in 18 of 19 dogs. A variety of changes were observed, the most typical being a
      patchy alveolar-interstitial pattern affecting the dorsocaudal lung fields.
      Angiostrongylus vasorum larvae were found in seven of 10 bronchoalveolar lavage
      specimens and 19 of 19 faecal samples. Three dogs died shortly after admission to
      the hospital. The remainder were successfully treated with fenbendazole at a dose
      of 50 mg/kg for five to 21 days. A vasorum should now be considered endemic to
      south-east England.

PMID- 15460202
TI  - Pneumonectomy: four case studies and a comparative review.
AB  - Pneumonectomy is the resection of all lung lobes in either the left or right lung
      field. The surgical technique and postoperative results of pneumonectomy for
      clinical disease have not been reported in companion animals. Pneumonectomy was
      performed in three dogs and one cat to treat pulmonary or pleural disease, and
      the postoperative outcome compared with the complications and results reported in
      the human literature. One dog died immediately postoperatively due to suspected
      respiratory insufficiency and the remaining three animals survived the
      perioperative period. Postoperative complications were reported in two animals.
      Cardiac complications occurred in the cat, with perioperative arrhythmias and
      progressive congestive heart failure. Gastrointestinal complications were
      diagnosed in one dog, with mediastinal shift and oesophageal dysfunction. Left-
      and right-sided pneumonectomy is feasible in companion animals, and the
      postoperative outcome and complications encountered in this series were similar
      to those reported in humans.

PMID- 15460203
TI  - Intramyocardial arterial narrowing in dogs with subaortic stenosis.
AB  - Earlier studies have described intramyocardial arterial narrowing based on
      hyperplasia and hypertrophy of the vessel wall in dogs with subaortic stenosis
      (SAS). In theory, such changes might increase the risk of sudden death, as they
      seem to do in heart disease in other species. This retrospective pathological
      study describes and quantifies intramyocardial arterial narrowing in 44 dogs with
      naturally occurring SAS and in eight control dogs. The majority of the dogs with
      SAS died suddenly (n=27); nine had died or been euthanased with signs of heart
      failure and eight were euthanased without clinical signs. Dogs with SAS had
      significantly narrower intramyocardial arteries (P<0.001) and more myocardial
      fibrosis (P<0.001) than control dogs. Male dogs and those with more severe
      hypertrophy had more vessel narrowing (P=0.02 and P=0.02, respectively), whereas
      dogs with dilated hearts had slightly less pronounced arterial thickening
      (P=0.01). Arterial narrowing was not related to age, but fibrosis increased with
      age (P=0.047). Dogs that died suddenly did not have a greater number of arterial
      changes than other dogs with SAS. This study suggests that most dogs with SAS
      have intramyocardial arterial narrowing and that the risk of dying suddenly is
      not significantly related to the overall degree of vessel obliteration.

PMID- 15460204
TI  - Two unusual tumours in a ferret (Mustela putorius furo).
AB  - This case report describes the clinical history, diagnosis and treatment of a
      ferret with a tumour of the right adrenal gland and insulinomas of the pancreas.
      Histopathology of both lesions confirmed the diagnoses. Clinical signs of the
      adrenal gland tumour were a swollen vulva, overgrooming, sexual activity and
      pruritus. The clinical signs suggesting insulinomas were collapse of the ferret,
      disorientation and ptyalism. A low blood glucose level assisted the diagnosis of
      insulinomas. This is believed to be the first reported case of concurrent
      insulinomas and adrenal gland tumour in a ferret in the United Kingdom.

PMID- 15460205
TI  - Plexogenic pulmonary arteriopathy in a Pembroke Welsh corgi.
AB  - A 21-month-old, male Pembroke Welsh corgi was referred for investigation of
      respiratory distress and progressive lethargy. Cardiac evaluation revealed a
      grade 4 pansystolic murmur over the left and right heart base. A heart murmur,
      dyspnoea, cyanosis, prolonged capillary refill time and ascites led to the
      tentative diagnosis of a cardiac malformation with a right-to-left shunt, with
      likely additional pulmonary disease. Pulmonary hypertension became evident during
      echocardiography, when the estimated systolic pulmonary artery pressure was over
      70 mmHg. Angiography revealed abnormal pulmonary vascular markings consistent
      with pulmonary hypertension and a small right-to-left shunting patent ductus
      arteriosus (PDA). The diagnosis of PDA was confirmed at postmortem examination.
      Histology of the pulmonary arteries showed lesions of plexogenic pulmonary
      arteriopathy. The question of whether both conditions were separate or part of
      the same clinical syndrome is discussed in this report.

PMID- 15460206
TI  - Pericardial effusion and cardiac tamponade in a cat with extranodal lymphoma.
AB  - A five-year-old domestic longhaired cat was evaluated for a seven-day history of
      worsening respiratory distress. Serum analysis for feline leukaemia virus antigen
      was positive. Pleural effusion was detected on thoracic radiographs and
      echocardiography revealed a pericardial effusion and cardiac tamponade.
      Cytological evaluation of the pleural and pericardial effusions showed
      lymphoblastic cells indicative of disseminated lymphoma. Following
      thoracocentesis and pericardiocentesis, the cat was treated for lymphoma using
      the University of Wisconsin-Madison chemotherapy protocol. The cat was sent home
      after three days and, at the time of writing (six months after initial
      presentation), was still symptom free. To the authors' knowledge, this is the
      first report confirming pericardial effusion and cardiac tamponade in the cat as
      a direct result of an extranodal lymphoma with cytological evidence of neoplastic
      cells in the pericardial fluid.

PMID- 15460207
TI  - Setting standards for good veterinary practice.

PMID- 15460208
TI  - Veterinary practice in Hong Kong.

PMID- 15460209
TI  - Clinical study on the effects of nizatidine on gastric motility and cardiac
      autonomic function. Investigations using electrogastrography and spectral
      analysis of heart rate variability.
AB  - Nizatidine (CAS 76963-41-2, Acinon), an H2 receptor antagonist, not only inhibits
      acid secretion but also improves gastrointestinal motility. However, autonomic
      nervous function has not been studied in detail using electrogastrography (EGG).
      In the present study, two protocols were adopted to study nizatidine's effects on
      cardiac autonomic function and gastric motility. Protocol I--Acute: "Group C-I":
      10 healthy volunteers received a single oral dose of nizatidine 150 mg. Protocol
      II--Chronic: "Group DM without N": 15 patients with diabetes mellitus (DM) were
      observed prior to administration of nizatidine. "Group DM with N": The same 15
      patients with DM received nizatidine 300 mg/day for more than 30 days. "Group C
      II": This control group was composed of 15 healthy volunteers not receiving
      nizatidine. In all groups, EGGs were recorded before and after a meal, and
      autonomic nervous function and QT interval of ECG dispersions were simultaneously
      evaluated. In Group C-I, nizatidine significantly increased the peak power
      amplitude of 3 cycles/min (cpm) frequency, but did not significantly change the
      dominant frequency of the 3-cpm waves. In Group DM with N, nizatidine
      administration significantly increased the peak power amplitude from 2.4 cpm or a
      lower frequency (bradygastria) to 3 cpm. Prior to nizatidine administration but
      after eating a meal, the peak power amplitude on EGG was not increased in Group
      DM without N. In Group DM with N, however, the EGG peak power amplitude increased
      to levels similar to those of the healthy subjects (Group C-II). Neither the
      single nor the chronic administration of nizatidine significantly prolonged the
      QT interval or increased the QT dispersion. A spectral analysis of heart rate
      variability showed that nizatidine administration, whether acute or chronic, did
      not significantly change the indices of autonomic nervous activity. Nizatidine
      may promote gastric emptying by inhibiting acetylcholine esterase, thus
      increasing cholinergic activity, and by acting directly on gastric smooth muscle.
      The results indicate that because nizatidine increases gastric motility without
      exerting a negative influence on the autonomic nerves, it may be a useful drug in
      patients with diabetic neuropathy.

PMID- 15460210
TI  - Suppressive activity of fexofenadine hydrochloride on the production of
      eosinophil chemoattractants from human nasal fibroblasts in vitro.
AB  - The influence of fexofenadine hydrochloride (FEX; CAS 138452-21-8) on the
      production of eosinophil chemoattractants, RANTES and eotaxin, from nasal polyp
      fibroblasts (NPFs) was examined in vitro. Seventh to tenth generation NPFs were
      cultured with or without 1 microg/ml lipopolysaccharide (LPS) in the presence of
      various concentrations of FEX. After 24 h, the culture supernatants were obtained
      and assayed for eosinophil chemoattractants by enzyme-linked immunosorbent assay
      (ELISA). FEX at a dose of more than 250 ng/ml (but not 100 ng/ml) inhibited
      RANTES and eotaxin production in response to LPS stimulation, when the agent was
      added at starting of cell cultures. FEX also showed suppressive effect on RANTES
      and eotaxin production from NPFs after stimulation with tumor necrosis factor
      alpha (TNF-alpha). However, the addition of FEX at 12 h after culture could not
      inhibit factor production. The influence of FEX on messenger RNA (mRNA)
      expression in NPFs was then examined. The addition of FEX at 100 ng/ml scarcely
      affected the expression of RANTES and eotaxin mRNA. On the other hand, 250 ng/ ml
      of FEX significantly inhibited these mRNA expressions that were enhanced by LPS
      stimulation.

PMID- 15460211
TI  - Comparison of two different preparations of ibuprofen with regard to the time
      course of their analgesic effect. A randomised, placebo-controlled, double-blind
      cross-over study using laser somatosensory evoked potentials obtained from UW
      irritated skin in healthy volunteers.
AB  - In the treatment of painful conditions the time to onset of a drug's analgesic
      effect is of great relevance. Plain ibuprofen acid (Ibu, CAS 15687-27-1) is
      relatively slowly absorbed after oral administration (t(max) is about 90-120
      min). If, however, ibuprofen is given in form of a lysine salt, absorption is
      much quicker. It has been shown in pharmacokinetic studies that the maximum
      plasma concentration after administration of an ibuprofen lysine tablet (IbuLys)
      is reached at about 35 min after oral administration. The aim of this study was
      to evaluate the onset and extent of the analgesic effect of 400 mg ibuprofen
      administered as marketed ibuprofen lysine tablets (two tablets of Dolormin as a
      single dose) in comparison with standard Ibu tablets (two tablets as a single
      dose) and placebo (Plc) utilising the objective, quantitative (high resolution)
      method of Laser algesimetry. The N1-P2 peak-to-peak amplitude of the Laser
      induced somatosensory evoked potentials (LSEPs)--measured during the first two
      hours after administration of study drugs--was the main efficacy parameter for
      the onset of the analgesic effects. The values obtained during 5 h after
      administration of the study drugs were used to measure the extent of the
      analgesic effects. As a main result with respect to the onset of analgesic
      action, the reduction of the N1-P2 peak-to-peak amplitude was significantly and
      relevantly more pronounced during the first 2 h after administration of IbuLys
      than after Ibu (IbuLys vs. Plc: p < or = 0.0020, IbuLys vs. Ibu: p < or =
      0.0366). During the same time the amplitudes of the single N1-components of the
      LSEPs were also significantly smaller after IbuLys than after Plc (p < or =
      0.0031) whereas the difference between plain Ibu and Plc was not significant (p <
      or = 0.1027). As a measure of the extent of analgesic action, the N1-P2 peak-to
      peak amplitudes recorded during 5 h after medication were more effectively
      reduced by IbuLys than by Ibu (IbuLys vs. Plc: p < or = 0.0001, IbuLys vs. Ibu: p
      < or = 0.0041, Ibu vs. Plc: p (0.383). The reduction of the amplitudes of the
      single N1-components by IbuLys was significant in comparison to Plc (p < or =
      0.0031), but not in comparison to Ibu. During the time of 5 h after medication
      the attenuating (analgesic) effect of IbuLys on the amplitude of the P2 component
      of the LSEPs was stronger than that of Plc (p < or = 0.0053) and stronger than
      that of Ibu (p < or = 0.0058). In summary IbuLys was significantly superior to
      Ibu with respect to the onset and extent of the analgesic effect. drugs were used
      to measure the extent of the analgesic effects. superior to Ibu with respect to
      the onset and extent of the analgesic effect.

PMID- 15460212
TI  - Synthesis and anti-implantation activity of new stilbene derivatives.
AB  - New stilbene (CAS 56-53-1) derivatives have been synthesized by reductive
      elimination of desoxybenzoin analogs which were obtained by Fries rearrangement
      of the corresponding phenolic esters. The chemical structures of the compounds
      obtained were confirmed by 1H-NMR, IR and elemental analysis. Anti-implantation
      activity of the compounds was determined by performing experiments with adult
      male and female Spargue-Dawley rats of proven fertility. A 67% inhibition of
      implantation was observed separately with compounds 3f and 3i.

PMID- 15460213
TI  - [Efficacy and safety of long-term complementary treatment with standardized
      European mistletoe extract (Viscum album L.) in addition to the conventional
      adjuvant oncologic therapy in patients with primary non-metastasized mammary
      carcinoma. Results of a multi-center, comparative, epidemiological cohort study
      in Germany and Switzerland].
AB  - OBJECTIVES: The purpose of the study was to evaluate the therapeutic efficacy and
      safety of long-term complementary therapy in primary, non-metastatic mammary
      carcinoma patients in UICC stage I-III with a standardized European mistletoe
      extract (Viscum album L., Iscador, "mistletoe extract") given in addition to
      conventional adjuvant oncologic therapy (i.e. chemo-, radio-, and hormonal
      therapy; "conventional therapy"). METHODS: The multicenter, comparative,
      retrolective, pharmaco-epidemiological cohort study with parallel groups design
      and randomly selected centers was carried out according to Good Epidemiological
      Practice (GEP) rules. The test group patients received subcutaneous mistletoe
      extract injections for at least three months in addition to the conventional
      therapy, while the control group was treated with conventional therapy only. The
      patients were followed up for at least three years or until death. The primary
      endpoint for efficacy was the overall incidence of adverse drug reactions (ADRs)
      attributed to the conventional therapy. Secondary endpoints were symptoms
      associated with disease and treatment, as well as the survival. All end-points
      were adjusted to baseline imbalance, therapy regimen and other confounders by the
      logistic regression or the Cox proportional hazard regression. Safety was
      assessed by the number of patients with ADRs attributed to the mistletoe extract
      treatment, the ADR severity and the evaluation of a possible tumor enhancement.
      RESULTS: 1442 patients (710 tests and 732 controls) were eligible for the "per
      protocol" analysis of efficacy and safety. At baseline, the mistletoe extract
      group had a more advanced disease and worse prognostic factors profile. After a
      median follow up of 67 vs. 61 months, and a median mistletoe extract therapy
      duration of 52 months, significantly fewer test group patients (16.3%) than
      control patients (54.1%) developed one or more ADRs attributed to the
      conventional therapy (adjusted odds ratio (95% confidence interval, CI): OR =
      0.47 (0.32-0.67), p < 0.001). In the mistletoe extract group, several symptoms
      more frequently disappeared, and the overall estimated survival was significantly
      longer (adjusted mortality hazard ratio (95% CI): HR = 0.46 (0.22-0.96), p =
      0.038). Systemic ADRs attributed to the mistletoe extract treatment developed
      0.8%, and local ADRs 17.3% of the patients. The ADR severity was mild to
      intermediate (WHO/CTC grade 1-2). Severe mistletoe extract therapy-related ADRs
      or tumor enhancement were not observed. CONCLUSIONS: The results of the present
      study confirmed the safety of the complementary therapy of patients with primary,
      non-metastatic mammary carcinoma with a standardized mistletoe extract and showed
      considerably fewer ADRs attributed to concurrent conventional therapy, as well as
      reduced disease and treatment-associated symptoms, and suggested a prolonged
      overall survival in the mistletoe extract group as compared with controls.

PMID- 15460214
TI  - The perfused everted intestinal segment of rat. 1st communication: absorption
      kinetics of markers of different permeation mechanisms.
AB  - The optimisation of the intestinal absorption of drugs represents one of the most
      important steps in the development of new pharmacologically active products.
      Several in vitro models are commonly used to study the mechanisms involved in
      drug absorption and all have advantages and disadvantages, notably they are often
      very static, and rarely take into account the intestinal motility and blood flow.
      The aim of this project was to validate a new ex vivo/in vitro model to study
      drug absorption, the perfused everted intestinal segment of rat, using three
      absorption markers: antipyrine (CAS 60-80-0) for passive transcellular diffusion,
      mannitol (CAS 69-65-8) for the paracellular diffusion and digoxin (CAS 20830-75
      5) as a P-glycoprotein substrate. The mean apparent permeabilities (P(app)) for
      the markers were 6.07 (+/- 0.99) x 10(-5), 8.79 (+/- 0.28) x 10(-6) and 3.1 (+/-
      0.85) x 10(-5) cm/s, respectively. The model is simple to establish and gives
      excellent absorption kinetics (r2 > 0.99), providing a valuable tool to study
      drug absorption during preclinical development, and subsequently the effects of
      different pharmaceutical formulations on that absorption.

PMID- 15460215
TI  - Trial logistics, implementation, and conduct of the OCTAVE mega study in Germany.
      Prospective, randomised, double-blind study to compare the efficacy and
      tolerability of omapatrilat and enalapril.
AB  - Using the example of the largest clinical trial so far conducted to obtain
      marketing approval (OCTAVE--Omapatrilat Cardiovascular Treatment Assessment
      Versus Enalapril) this paper describes the way the trial was conducted in Germany
      and the set-up of the trial logistics. OCTAVE was a prospective, randomised,
      double-blind study in which the efficacy and tolerability of omapatrilat (CAS
      167305-00-2) compared to enalapril (CAS 75847-73-3) were studied in 25 302
      patients with uncontrolled blood pressure. Patient recruitment was completed on
      schedule in just under four months in this global study. An appropriate study
      design, tailor-made logistics, a special monitoring system and effective project
      and data management allowed the selection and initiation of 430 study centres in
      Germany. As a result 4868 patients were randomised within about six months of
      finalising the study protocol.

PMID- 15460216
TI  - Expression, purification, biochemical and pharmacological characterization of a
      recombinant aprotinin variant.
AB  - Aprotinin (GAS 9087-70-1) is known as a potent inhibitor of serine proteases such
      as trypsin, plasmin, tissue and plasma kallikrein. In this study, an aprotinin
      variant was designed by means of rationale mutagenesis that differs from
      aprotinin by two amino acids in the active site and by seven amino acids in the
      backbone. The recombinant protein is expressed in a secretory yeast system
      enabling large scale production. A purification procedure was developed to yield
      high amounts of pure and correctly processed aprotinin variant. The changes in
      the active site of the aprotinin variant increase the potency towards inhibition
      of plasma kallikrein whereas the inhibition of plasmin is only marginally
      reduced. The net charge of the molecule is reduced from the basic (IP 10.5) to
      the neutral range (IP 5.6). The recombinant aprotinin variant shows a decrease of
      immunogenicity in several models. No cross-reactivity with human and rabbit
      antibodies directed against aprotinin was observed both in in vivo and in ex vivo
      studies. In addition, the variant is more potent in a rat brain edema model of
      acute subdural hematoma compared to aprotinin.

PMID- 15460217
TI  - Health concepts.

PMID- 15460218
TI  - Introduction to nursing science.

PMID- 15460219
TI  - Nursing information technology: classifications and management.

PMID- 15460220
TI  - The International Classification For Nursing Practice.

PMID- 15460221
TI  - A nursing minimum data set.

PMID- 15460222
TI  - Data analysis methods.

PMID- 15460223
TI  - Epidemiological study designs.
AB  - This chapter illustrates the study designs most frequently encountered in the
      medical literature. In medical research, either subjects are observed or
      experiments are undertaken. Experiments involving humans are called trials.
      Experimental studies may also use animals and tissue, although we did not discuss
      them as a separate category; the comments pertaining to clinical trials are
      relevant to animal and tissue studies as well. Each type of study discussed has
      advantages and disadvantages. Randomized, controlled clinical trials are the most
      powerful designs possible in medical research, but they are often expensive and
      time-consuming. Well-designed observational studies can provide useful insights
      on disease causation, even though they do not constitute proof of causes. Cohort
      studies are best for studying the natural progression of disease or risk factors
      for disease; case-control studies are much quicker and less expensive. Cross
      sectional studies provide a snapshot of a disease or condition at one time, and
      we must be cautious in inferring disease progression from them. Surveys, if
      properly done. are useful in obtaining current opinions and practices. Case
      series studies should be used only to raise questions for further research.

PMID- 15460224
TI  - Statistical methods.
AB  - The purpose of this chapter is to present a conceptual framework that applies to
      almost all statistical procedures discussed so far in this text. We also describe
      briefly, using a conceptual framework only, some of the more advanced techniques
      used in medicine.

PMID- 15460225
TI  - Classification methods.
AB  - This chapter describes all the recent advances in statistical and syntactic
      pattern recognition, along with a number of the most important hybrid efforts in
      pattern recognition methodology, which together with structural pattern
      recognition, are the future trends in pattern recognition applications' schemes.

PMID- 15460226
TI  - Health informatics.

PMID- 15460227
TI  - Hospital information systems.

PMID- 15460228
TI  - Specialised information systems: diabetes care.
AB  - This chapter describes some of the ways in which IT can be applied to the
      clinical management of diabetes, considering both clinical information management
      and decision support. At a methodological level issues addressed range from
      requirements analysis and specification to evaluation. From a clinical
      perspective the benefits that can arise and the challenges still to be faced are
      discussed. It is clear from practice that the dominant feature determining
      success is 'clinical usefulness' combined with 'safety' -the methods of
      evaluating clinical systems are in their infancy and need further development.
      Creating clinically useful and effective systems is more difficult than is
      commonly anticipated. The poor level of investment in this area is reflected in
      the relatively poor penetration of IT into clinical practice.

PMID- 15460229
TI  - Electronic health record.
AB  - The chapter covers the electronic health record and electronic health record
      system that facilitates the use of EHR. The EHR is compared with the traditional
      handwritten health care record. Definition of Electronic Health Records and its
      association with the terminology, classification and coding is presented. The
      architecture of the Electronic Health Record is of strong significance as well as
      its attributes. Strategic approaches of designing systems supporting the use of
      electronic health records are depicted. A short presentation of current state of
      implementation and the obstacles for further implementation are given in the
      final part of the chapter.

PMID- 15460230
TI  - Nursing Information System.
AB  - Nursing Information System (NIS) is a part of a health care information system
      that deals with nursing aspects, particularly the maintenance of the nursing
      record. The several objectives that a Nursing Information system should meet in
      order to succeed its aims, cover the users' needs and operate properly are
      described. The functions of such systems, which combine with the basic tasks of
      the nursing care process, are examined. As Nursing Information System is part of
      the health care and hospital information system, the different strategies and
      approaches for designing and developing Hospital Information Systems followed
      from the decade of 1970 until the recent decade of 1990, are presented. The three
      main approaches followed were the "centralized approach", the "departmental
      approach", and the "distributed approach". The advantages and drawbacks of each
      different approach are examined. For the implementation or upgrade of Nursing
      Information System a NIS committee comprised by different health care
      professionals, is necessary to be formed. The implementation and upgrade of a
      Nursing Information System follows some specific phases. These steps, include
      planning phase, analysis phase, design phase, development phase, implementation
      phase, and upgrade phase. A paragraph at the end of this chapter summarizes the
      future trends of Nursing Information Systems.

PMID- 15460231
TI  - Human interaction.

PMID- 15460232
TI  - Electronic data interchange.

PMID- 15460233
TI  - Telecare services for nursing.

PMID- 15460234
TI  - Image processing and analysis.

PMID- 15460235
TI  - Knowledge representation and nursing informatics.

PMID- 15460236
TI  - Multimedia technologies in education.
AB  - In general multimedia is the combination of visual and audio representations.
      These representations could include elements of texts, graphic arts, sound,
      animation, and video. However, multimedia is restricted in such systems where
      information is digitalized and is processed by a computer. Interactive multimedia
      and hypermedia consist of multimedia applications that the user has more active
      role. Education is perhaps the most useful destination for multimedia and the
      place where multimedia has the most effective applications, as it enriches the
      learning process. Multimedia both in nursing education and in medical informatics
      education has several applications as well. A multimedia project can be developed
      even as a "stand alone" application (on CD-ROM), or on World Wide Web pages on
      Internet. However several technical constraints exist for developing multimedia
      applications on Internet. For developing multimedia projects we need hardware and
      software, talent and skill. The software requirements for multimedia development
      consist of one or more authoring systems and various editing applications for
      text, images, sounds and video. In this chapter different software tools for
      creating multimedia applications are presented. In the last part of this chapter,
      two examples of multimedia educational training programs are discussed. Both are
      "stand alone" applications (CD-ROMs). The first, examines several aspects of the
      electronic patient record by using videos, audio descriptions, lectures and
      glossary, while the second one presents several topics regarding epidemiology and
      epidemiological research by using graphics, sound and animation.

PMID- 15460237
TI  - Health care systems.

PMID- 15460238
TI  - Organizational impact of health information systems in healthcare.

PMID- 15460239
TI  - The impact of communications and information technology on organisations.

PMID- 15460240
TI  - Impact in nursing environment.

PMID- 15460241
TI  - Quality assurance issues.

PMID- 15460242
TI  - Communication among health care professionals.

PMID- 15460243
TI  - Data protection and confidentiality.

PMID- 15460244
TI  - Education in health and nursing informatics.
AB  - This chapter focused on some of the key issues of Health and Nursing Informatics
      Education. First an historical overview of Health and Nursing Informatics
      Education is presented. We also describe briefly the activities in the domain of
      Nursing Informatics Education across Europe. The Special Projects for Health and
      Nursing Informatics in Europe are presented. Because of the variety of
      educational systems, the International Medical Informatics Association (IMIA)
      felt the need to develop international recommendations in health and medical
      informatics education. From a nursing informatics perspective, the IMIA
      recommendations in Nursing Informatics Education are discussed.

PMID- 15460245
TI  - High pH-resistant, surface-bonded sol-gel titania hybrid organic-inorganic
      coating for effective on-line hyphenation of capillary microextraction (in-tube
      solid-phase microextraction) with high-performance liquid chromatography.
AB  - Sol-gel titania-poly(dimethylsiloxane) (TiO2-PDMS) coating was developed for
      capillary microextraction (CME) to perform on-line preconcentration and HPLC
      analysis of trace impurities in aqueous samples. A method is presented describing
      in situ preparation of the titania-based sol-gel PDMS coating and its
      immobilization on the inner surface of a fused silica microextraction capillary.
      To perform CME-HPLC, the sol-gel TiO2-PDMS capillary was installed in the HPLC
      injection port as an external sampling loop, and a conventional ODS column was
      used for the liquid chromatographic separation. The target analytes were
      extracted on-line by passing the aqueous sample through this sampling loop. The
      sol-gel titania-PDMS coated capillaries were used for on-line extraction and HPLC
      analysis of polycyclic aromatic hydrocarbons, ketones, and alkylbenzenes. The
      extracted analytes were then transferred to the HPLC column using an organic-rich
      mobile phase followed by HPLC separation via gradient elution. To our knowledge,
      this is the first report on the use of sol-gel titania-based organic-inorganic
      material as a sorbent in capillary microextraction. The newly developed sol-gel
      titania-based CME coatings demonstrated excellent pH stability and enhanced
      extraction capability over the commercial GC coatings that are conventionally
      used for the same purpose. Extraction characteristics of a sol-gel titania-PDMS
      capillary remained practically unchanged after continuous rinsing with a 0.1 M
      NaOH solution (pH 13) for 12h.

PMID- 15460246
TI  - Molecularly imprinted solid-phase extraction of naphthalene sulfonates from
      water.
AB  - A new polymeric sorbent synthesised by exploiting molecular imprinting technology
      has been used to selectively extract naphthalene sulfonates (NSs) directly from
      aqueous samples. In the non-covalent molecular imprinting approach used to
      prepare this polymer, 1-naphthalene sulfonic acid (1-NS) and 4-vinylpyridine (4
      VP) were used as a template molecule and functional monomer, respectively, and
      both dissolved in a mixture of methanol/water (4:1) as porogen together with the
      cross-linker ethylene glycol dimethacrylate. The new non-covalent molecularly
      imprinted polymer (MIP) prepared in aqueous environment was used as a sorbent in
      solid-phase extraction (SPE) to selectively extract a group of naphthalene mono-
      and disulfonates. When one litre of a standard aqueous solution, which contained
      a mixture of eight NSs, was percolated through the SPE cartridge, all the NSs
      were retained on the MIP because of the cross-reactivity of the polymer.
      Recoveries were higher than 80% for all the compounds even after a clean-up step
      with methanol (MeOH). The MIP was also used to analyse water from the Ebro river.

PMID- 15460247
TI  - Simplified procedures for the analysis of polycyclic aromatic hydrocarbons in
      water, sediments and mussels.
AB  - We describe in this paper simple and robust analytical protocols to determine the
      16 polycyclic aromatic hydrocarbons (PAHs) of the US Environmental Protection
      Agency priority list in water, sediment and mussels. For water samples, eight
      different solid-phase extraction (SPE) sorbents have been compared and among
      them, C18 provided highest recoveries and limits of detection of 0.3-15 ng/L. For
      lyophilized sediments, Soxhlet and ultrasonic extraction were compared, and the
      last one permitted to recover all analytes with highest repetitivity and was
      validated by analysing a certified reference material. Finally, the analysis of
      mussels was undertaken using Soxhlet, ultrasonic and pressurized liquid
      extraction (PLE) and the performance of several clean-up steps are compared.
      Whereas for the former two, incomplete recovery or losses of some analytes were
      evidenced, PLE permitted a more efficient extraction and although alkaline
      digestion was necessary to remove coextracted compounds, the method gave
      acceptable recoveries and limits of detection of 0.5-7.7 microg/kg dry mass, as
      for sediments. In all cases, analysis was performed by gas chromatography coupled
      to mass spectrometry and internal standard quantification was performed using
      five deuterated PAHs. Each method performance is discussed for the three matrices
      analysed and the paper reports advantages and disadvantages of each for their
      routine application in monitoring programs.

PMID- 15460248
TI  - Hollow fiber membrane-protected solid-phase microextraction of triazine
      herbicides in bovine milk and sewage sludge samples.
AB  - A porous polypropylene hollow fiber membrane (HFM)-protected solid-phase
      microextraction (HFM-SPME) procedure in conjunction with gas chromatography/mass
      spectrometric analysis for use in the determination of triazine herbicides in
      bovine milk samples is described. A 65-microm polydimethylsiloxane-divinylbenzne
      (PDMS-DVB) SPME fiber was protected by an HFM. HFM-SPME experimental parameters
      such as fiber type, extraction time, extraction temperature and salt
      concentration were investigated and optimized. The relative standard deviations
      for the reproducibility of the optimized HFM-SPME method varied from 4.30 to
      12.37%. The correlation coefficients of the calibration curves were between
      0.9799 and 0.9965 across a concentration range of 0-200 microg l(-1). The method
      detection limits for triazines in bovine milk were in the range of 0.003-0.013
      microg l(-1) and limits of quantification were in the range of 0.006-0.021 microg
      l(-1). The suitability of HFM-SPME was extended to the analysis of the herbicides
      in sewage sludge samples. The results demonstrate that HFM-SPME was an efficient
      pretreatment and enrichment procedure for complex matrices.

PMID- 15460249
TI  - Pressurized liquid extracts from Spirulina platensis microalga. Determination of
      their antioxidant activity and preliminary analysis by micellar electrokinetic
      chromatography.
AB  - In this work, different extracts from the microalga Spirulina platensis are
      obtained using pressurized liquid extraction (PLE) and four different solvents
      (hexane, light petroleum, ethanol and water). Different extraction temperatures
      (115 and 170 degrees C) were tested using extraction times ranging from 9 to 15
      min. The antioxidant activity of the different extracts is determined by means of
      an in vitro assay using a free radical method. Moreover, a new and fast method is
      developed using micellar electrokinetic chromatography with diode array detection
      (MEKC-DAD) to provide a preliminary analysis on the composition of the extracts.
      This combined application (i.e., in vitro assays plus MEKC-DAD) allowed the fast
      characterization of the extracts based on their antioxidant activity and the UV
      vis spectra of the different compounds found in the extracts. To our knowledge,
      this work shows for the first time the great possibilities of the combined use of
      PLE-in vitro assay-MEKC-DAD to investigate natural sources of antioxidants.

PMID- 15460250
TI  - Direct detection of trace haloacetates in drinking water using microbore ion
      chromatography. Improved detector sensitivity using a hydroxide gradient and a
      monolithic ion-exchange type suppressor.
AB  - A highly sensitive gradient microbore ion chromatographic method was developed
      with electrolytically generated hydroxide eluents for the determination of low
      microg/L levels of chloroacetate, bromoacetate, trifluoroacetate,
      dichloroacetate, chlorodifluoroacetate, dibromoacetate, trichloroacetate,
      bromodichloroacetate and dibromochloroacetate disinfectant by-products formed as
      a result of chlorination of drinking waters. The possibility of using a packed
      bed Dionex Atlas suppressor with a hydroxide gradient at microbore flow rates was
      investigated in order to reduce baseline noise levels. The Atlas suppressor
      displayed a very significant reduction in noise levels compared to the standard
      alternative ASRS Ultra suppressor, reducing noise by a factor of 15-20 in some
      cases, allowing trace haloacetic acids (HAs) to be seen with the direct injection
      of 100 microL of treated water, with prior chloride and sulfate removal. To lower
      detection limits even further, a solid phase extraction was employed to
      preconcentrate HAs, resulting in detection limits of between 0.09 and 21.5
      microg/L. The method was applied to the determination of HAs in environmental
      samples and standard addition curves for three drinking water samples were
      carried out for both direct injection and preconcentration methods. R2 values in
      both cases were > or =0.98. Combined content for US Environmental Protection
      Agency regulated HAs in the three drinking water samples from Dublin City
      University; New Ross, Co. Wexford and Drogheda, Co. Louth were 46.5, 58.3 and
      12.6 microg/L, respectively.

PMID- 15460251
TI  - Studies on the flavones using liquid chromatography-electrospray ionization
      tandem mass spectrometry.
AB  - Fragmentation pathways of nine flavone compounds have been studied by using
      electrospray ionization multi-stage tandem mass spectrometry (ESI-MSn). Analyzing
      the product ion spectra of flavonoids and aglycones, we observed some diagnostic
      neutral losses, such as CH3, H2O, residue of glucose and gluconic acid, which are
      very useful for the identification of the functional groups in the structures.
      Furthermore, specific retro Diels-Alder (RDA) fragments for flavones with
      different hydroxyl substitution have also been discussed. The information is
      helpful for the rapid identification of the location site of hydroxyl
      substitution on flavones. Fragmentation pathways of C-glycosidic flavonoid have
      also been discussed using ESI-MSn, demonstrating ions [M-H-60]-, [M-H-90]-, [M-H
      120]- are characteristic ions of C-glycosidic flavonoid. According to the
      fragmentation mechanism of mass spectrometry and HPLC-MS data, the structures of
      seven flavones in Scutellaria baicalensis Georgi have been identified on-line
      without time-consuming isolation. The HPLC-ESI-MSn method for analyzing
      constituents in the Scutellaria baicalensis Georgi has been established.

PMID- 15460252
TI  - Optimization of diagonal chromatography for recognizing post-translational
      modifications.
AB  - Post-translational modifications modulate the activity of most eukaryote
      proteins. Analysis of these modifications presents a formidable analytical
      challenge. This paper examines the potential of diagonal chromatography for
      recognizing post-translational modifications. Diagonal chromatography is the
      process of using the same chromatographic separation in two dimensions. Between
      the two dimensions, a chemical modification is applied to all fractions.
      Substances that have been modified are revealed by the change in their
      chromatographic properties between the two dimensions. When the modification is
      specific to a particular type of post-translational modification, peptides that
      carry the modification have the potential to be revealed. Changes in the
      retention time of modified peptides have to be large enough to be different from
      unmodified peptides. Tyrosine, serine, and threonine phosphorylation were
      identified with diagonal chromatography. Heptafluorobutyric acid was used as an
      ion-pairing agent to improve the selectivity between serine and threonine
      phosphorylated peptides and parent peptides after dephosphorylation. The diagonal
      chromatography method was also examined in the recognition of glycopeptides.
      However, changes of retention time after deglycosylation were considered to be
      too small to make this an unequivocal method for the study of glycosylation.

PMID- 15460253
TI  - Liquid chromatographic method for the analysis of two plant based insecticide
      synergists dillapiole and dihydrodillapiole.
AB  - A reversed-phase LC method for the determination of two plant based insecticide
      synergists dillapiole (5-allyl 6,7-dimethoxy 1,3-benzodioxole) and
      dihydrodillapiole (5-n-propyl 6,7-dimethoxy-1,3-benzodioxole) is reported. The
      resolution of dillapiole and dihydrodillapiole has been achieved on RP-18 column
      using methanol-water (90:10, v/v) as mobile phase and a photodiode array detector
      at 207 nm. The response was linear in the range of 25-250 microg. The developed
      isocratic RP-LC method was validated for specificity, linearity, precision, and
      accuracy. It has been applied for individual or simultaneous detection,
      monitoring and quantification of dillapiole and dihydrodillapiole from treated
      French bean Phaseolus sp.

PMID- 15460254
TI  - Use of high-performance liquid chromatography to assess airborne mycotoxins.
      Aflatoxins and ochratoxin A.
AB  - An HPLC analytical method combining methanol-deionised water (80:20, v/v)
      extraction, methanol-acetonitrile (50:50, v/v) extraction and fluorescence
      detection was implanted to analyse ochratoxin A and aflatoxins B1, B2, G1 and G2
      of air samples collected during the usual production process in a number of
      workplaces of a coffee factory to assess the occupational exposure of the engaged
      workers. The average levels of airborne ochratoxin A and aflatoxins were less
      than 1.2 and 0.4 ng/m3, respectively, using 50 L air samples. When 150 L air
      samples were used, levels lower than 0.04 ng/m3 ochratoxin A and 0.013 ng/m3 for
      aflatoxins B1, B2, G1 and G2, could be detected.

PMID- 15460255
TI  - Simultaneous liquid chromatography-fluorescence analysis of type A and type B
      trichothecenes as fluorescent derivatives via reaction with coumarin-3-carbonyl
      chloride.
AB  - A method for the simultaneous LC-fluorescence detection (FLD) determination of
      eight trichothecenes A and B by pre-column derivatization with coumarin-3
      carbonyl chloride, a highly fluorescent fluorophore, has been developed. The
      reaction conditions (temperature, reaction time, reactant ratios) were optimized
      to give a reproducible quantitative conversion. All derivatives were
      characterized by LC-MS. The chromatographic parameters were optimized (column,
      eluent) to give a very good separation of three type A (diacetoxyscirpenol, T-2
      toxin, HT-2 toxin) and five type B trichothecenes [deoxynivalenol (DON),
      nivalenol, fusarenon-X, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol]. The
      best conditions were obtained on a narrow-bore C18 column with a water-methanol
      gradient. The detection limits (S/N = 3:1) in grain samples, with an injected
      volume of 5 microl, were 0.2-1 ng/g for all trichothecenes. These values are more
      than one order of magnitude lower than those of other LC-FLD and LC-MS methods
      and are similar to those obtained by GC-MS. The calibration curves were linear
      between 100 and 2500 ng/g. The method was successfully applied to the analysis of
      a certified wheat reference material, after solvent extraction and clean-up on a
      Mycosep column, obtaining a good recovery (89% for DON) and a high accuracy (z
      score value: 0.67).

PMID- 15460256
TI  - Preparative isolation and purification of chuanxiongzine from the medicinal plant
      Ligusticum chuanxiong by high-speed counter-current chromatography.
AB  - Ligusticum chuanxiong Hort has been used widely in traditional medicines for the
      treatment of various kinds of disorders such as cardiovascular and
      cerebrovascular diseases. High-speed counter-current chromatography was applied
      to the isolation and purification of the bioactive component chuanxiongzine from
      L. chuanxiong Hort. The crude chuanxiongzine was obtained by extraction with
      ethanol from the dried roots of L. chuanxiong Hort under sonication. Preparative
      high-speed counter-current chromatography with a two-phase solvent system
      composed of n-hexane-ethyl acetate-ethanol-water (5:5:3:7, v/v) was successfully
      performed yielding 11.5 mg chuanxiongzine at 96.8% purity from 300 mg of the
      crude extract (4.2% chuanxiongzine) with the recovery of 91% in a one-step
      separation.

PMID- 15460257
TI  - Evaluation of the pH effect of formulations on the skin permeability of drugs by
      biopartitioning micellar chromatography.
AB  - Dermal absorption of chemicals is an area of increasing interest for the
      pharmaceutical and cosmetic industries, as well as in dermal exposure and risk
      assessment processes. Biopartitioning micellar chromatography (BMC) is a mode of
      reversed phase micellar chromatography that has proved to be useful in the
      description and prediction of several pharmacological properties of xenobiotics
      including oral drug absorption, ocular and skin drug permeability. The present
      paper deals with the application of biopartitionig micellar chromatography to
      evaluate the pH effect on the skin permeability of twelve non-steroidal anti
      inflammatory drugs and lidocaine. For this purpose the BMC retention of the whole
      set of compounds at several pHs between 3.5 and 8 was obtained. Using the BMC
      retention-permeability model previously reported, the permeability of the
      compounds at different pH values was estimated. The predicted permeability values
      at different pH values for ketoprofen, lidocaine, salicylic acid and ibuprofen
      agree with those experimental reported in literature for these compounds using
      excised human and rat skin.

PMID- 15460258
TI  - Multiple-detector responses or multiple-retention times: what is more informative
      for gas chromatography peak identification?
AB  - Multiple-separation and -detection are two approaches applied at the
      identification of analytes in chromatography. Using them depends on the physico
      chemical properties and elemental content of the analytes. When physico-chemical
      properties are similar multiple-separation gives better opportunities for the
      identification. In this case, the efficiency of the columns is very important.
      When analytes contain some characteristic groups as--NO2, halogen, or nitrogen
      atoms then multiple-detection will be more useful. The sensitivity and/or
      selectivity of the detectors increase reliability of identification
      significantly.

PMID- 15460259
TI  - Application of solid-phase microextraction to the study of the photochemical
      behaviour of five priority pesticides: "on-fiber" and aqueous photodegradation.
AB  - Solid-phase microextraction (SPME) is applied to study the photochemical
      degradation of five priority pesticides: atrazine, alachlor, aldrin, dieldrin,
      endrin. Analyses were carried out by gas chromatography-mass spectrometry. The
      possibility of studying the photochemical degradation of the target compounds in
      solid-phase microextraction fibers, "photo-SPME", is evaluated employing
      different SPME coatings. The target analytes were extracted from aqueous
      solutions using different commercial coatings and then, the fibers were exposed
      to UV light. Results indicated that on-fiber photodegradation takes place in a
      considerably major extent using PDMS coating for an irradiation time of 30min. On
      fiber photodegradation kinetics of each analyte were determined by UV irradiation
      of the PDMS for different times. A large number of photoproducts were generated
      and they were tentatively identified by means of their mass spectra and with the
      aid of literature. In this way, main photodegradation mechanisms could be
      postulated. Aqueous photodegradation studies followed by SPME were performed and
      compared with photo-SPME. All the photoproducts detected in the aqueous
      experiments were previously found in the photo-SPME experiments. This study shows
      the potential of photo-SPME to evaluate the photo-transformation of organic
      pollutants.

PMID- 15460260
TI  - Quality assessment of Flos Chrysanthemi Indici from different growing areas in
      China by solid-phase microextraction-gas chromatography-mass spectrometry.
AB  - Flos Chrysanthemi Indici is a common traditional Chinese medicine (TCM). In this
      paper, headspace solid-phase microextraction coupled with gas chromatography-mass
      spectrometry (HS-SPME-GC-MS) was developed for quality assessment of Flos
      Chrysanthemi Indici from different growing areas in China. SPME parameters such
      as extraction fibers, extraction temperature, extraction time and sample mass
      were investigated to achieve identical results to those obtained by the steam
      distillation (SD). The selected SPME conditions were as follows: SPME fiber
      coated with 65-microm PDMS/DVB, extraction temperature of 60 degrees C,
      extraction time of 30 min and sample mass of 1.0 g. Furthermore, four active
      compounds (eucalyptol, camphor, borneol and bornyl acetate) presented in the TCM
      were applied to evaluating the quality of Flos Chrysanthemi Indici from 20
      various areas. The quality assessment was successfully performed to compare the
      similarity value (S) between different sample vector of Flos Chrysanthemi Indici
      and the standard profile vector (SPV). The results showed that the proposed HS
      SPME-GC-MS was an alternative technique for quality assessment of Flos
      Chrysanthemi Indici samples.

PMID- 15460261
TI  - Use of miniaturised isotachophoresis on a planar polymer chip to analyse
      transition metal ions in solutions from metal processing plants.
AB  - An electrolyte system, using malic acid as a complexing agent, has been developed
      to allow the determination of transition metal cations using miniaturised
      isotachophoresis. The method allowed the simultaneous determination of Mn2+,
      Cr3+, Fe2+, Co2+, Zn2+ and Ni2+ to be made without interference from other common
      ions. Limits of detection were calculated to be in the range 0.5-1.0mg l(-1) for
      Mn2+, Cr3+ Co2+ and Zn2+ and 2.0 mg l(-1) for Fe2+ and 4.7 mg l(-1) for Ni2+. The
      successful analysis of five industrial samples, containing a range of these metal
      ions, obtained from metal processing plants were achieved in under 13 min. The
      separations were performed on a poly(methyl methacrylate) chip with integrated
      platinum wire conductivity detection electrodes.

PMID- 15460262
TI  - Electrochromatographic studies of etched capillaries modified with a cyano
      pentoxy biphenyl liquid crystal.
AB  - A liquid crystal stationary phase for open tubular capillary electrochromatograpy
      (OTCEC) is fabricated by etching a fused silica tube and then bonding 4,4'
      cyanopentoxy biphenyl by a silanization/hydrosilation process. The versatility of
      this electrophoretic capillary is demonstrated by separations of proteins,
      peptides, basic pharmaceuticals and the metabolites of tryptophan.
      Chromatographic interactions are verified by resolution of two neutral peptides.
      Variable temperature studies are used to understand the liquid crystal properties
      of the bonded moiety. EOF measurements as a function of pH and temperature
      further characterize this unique separation media.

PMID- 15460263
TI  - Improved capillary electrophoretic separation of nine (fluoro)quinolones with
      fluorescence detection for biological and environmental samples.
AB  - A capillary electrophoretic method has been developed for the separation of nine
      (fluoro)quinolones. Detection is done by fluorescence measurement with broad
      wavelength band excitation between 240 and 400 nm. Best separation is achieved in
      a carrier electrolyte containing 50 mM H3PO4 adjusted to pH 7.55-acetonitrile
      (60:40, v/v). Detection limits are in the low microgl(-1) range. The suitability
      to real samples has been demonstrated by analyzing blood samples and surface
      water samples. Sample preconcentration and sample clean-up can easily be done by
      solid-phase extraction. Different phases based on alkyl- or phenyl-modified
      silica as well as on polymers have been investigated for this purpose. The method
      should also be useful for determination of residues of (fluoro)quinolones in food
      or other matrices.

PMID- 15460264
TI  - Determination of flavour and off-flavour compounds in orange juice by on-line
      coupling of a pervaporation unit to gas chromatography-mass spectrometry.
AB  - A method for the analysis of several volatiles compounds responsible for orange
      juice flavour (ethyl butanoate, limonene, linalool, alpha-pinene, geranial, neral
      and alpha-terpineol) has been developed. The isolation of this compounds was
      carried out by pervaporation (PV) followed by on-line gas chromatography-mass
      spectrometry (GC-MS). The coupling PV-GC-MS has been successfully applied to
      fresh hand-squeezed orange juices and frozen concentrated ones in order to
      establish differences in their flavour profile. Method has been validated with
      recovery spike experiments which showed its applicability for a wide range of
      concentrations.

PMID- 15460265
TI  - Morinda revisited: changes in nutritional well-being and gender differences after
      30 years of rapid economic growth in rural Punjab, India.
AB  - A follow-up study of malnutrition and its determinants among children 6 to 24
      months of age was carried out in rural areas of Punjab State in India 30 years
      after the original study, and following a period of rapid economic growth. The
      original 1971 study had found a high prevalence of mortality and malnutrition and
      the worst gender difference in nutritional status ever recorded in an Indian
      study. The 2001 follow-up study found dramatic reductions in child mortality,
      child malnutrition, gender-based imbalances in child well-being and care, and
      family size, the result of participatory economic growth coupled with broad-based
      educational, health, and family-planning services. Despite overall improvements
      in caloric intake, however, 40% of lower-class children in 2001 were still
      consuming less than 50% of their caloric allowance. With minimal gender-based
      abortion and significantly reduced neglect and mortality offemale children,
      gender balance among children in this area of rural Punjab improved markedly over
      the 30-year period.

PMID- 15460266
TI  - Behavior-change trials to assess the feasibility of improving complementary
      feeding practices and micronutrient intake of infants in rural Bangladesh.
AB  - This study used simple rapid-assessment techniques to test the feasibility of
      increasing the consumption of complementary foods by infants by asking mothers to
      increase meal quantity or frequency or by altering the viscosity/energy density
      of the food. The feasibility of using micronutrient supplements either added
      directly to food or administered as liquid drops was also examined. The study was
      conducted in rural Bangladesh and involved four separate short-term behavioral
      change trials. Depending on the trial, fieldworkers recruited 30 to 45 infants 6
      to 12 months of age. Following recommendations to increase the amount of food
      provided to infants, the mean intakes from single meals increased from 40 +/- 23
      g on day 1 to 64 +/- 30 g on day 7 (p < 0.05). In a second trial, the mean meal
      frequency increased from 2.2 +/- 1.3 on day 1 to 4.1 +/- 1.3 on day 7 (p < 0.05).
      Provision of high-energy-density diets, prepared by decreasing viscosity with
      alpha-amylase or by hand-mashing rice and dhal into a paste before feeding,
      increased single-meal energy consumption from 54 +/- 35 kcal to 79 +/- 52 kcal or
      75 +/- 37 kcal (p < 0.05), respectively. Both types of micronutrient supplements
      were well accepted and used according to recommendations. In conclusion, it was
      possible to change short-term child-feeding behaviors to promote increased food
      intake, mealfrequency, energy density, and micronutrient consumption. Because
      each of these interventions lasted for only about 1 week, however, the long-term
      sustainability of these changes is not known. Moreover, the effect of increased
      feeding of complementary foods on intakes of breastmilk and total daily
      consumption of energy and nutrients requires further study.

PMID- 15460267
TI  - Ecuadorian Andean women's nutrition varies with age and socioeconomic status.
AB  - An agricultural project in Highland Ecuador provided a model context to better
      understand the nutrition of rural women. The adequacy of women's nutrition and
      the strength of associations with age and socioeconomic status were studied in
      104 rural households over four rounds (two seasons) during the 1995-1996
      agricultural year using a cross-sectional with repeated-measures design. Women
      were at high risk for micronutrient deficiencies (calcium, iron, riboflavin, and
      vitamin B12) due to low intakes of animal products. Two distinct constructs
      representing socioeconomic status were identified: modern lifestyle and farming
      wealth. In multivariate models, farming wealth was associated with quality of
      women's diet (animal protein adjusted for energy, p = 0.01). Diet quality, in
      turn, was positively associated with anthropometric status (p = 0.02). Women over
      the age of 50 weighed approximately 3.7 kg less than younger women and consumed
      less energy (300 kcal) and micronutrients (p < 0.05). Age was positively
      associated with respiratory morbidity (p = 0.01). These findings, while directly
      relevant to a specific context, suggest the need for cross-cultural studies to
      identify the extent of, and factors contributing to, the risk of nutritional
      inadequacy in postreproductive women in developing countries.

PMID- 15460268
TI  - Children aged 6 to 60 months in Nepal may require a vitamin A supplement
      regardless of dietary intake from plant an animal food sources.
AB  - The purpose of this survey was to explore the relationship between the prevalence
      of the health indicators of malnutrition, diarrhea, and acute respiratory
      infection and the consumption of vitamin A-rich food and the supplementation
      status of three groups of children in Nepal (supplemented, supplemented only
      once, and never supplemented). A trained female community health worker
      interviewed mothers about vitamin A-rich food feeding practices to children aged
      6 to 60 months using a standardized questionnaire and then estimated the
      nutritional status of the children using mid-upper-arm circumference measurements
      and recording the incidence of diarrhea and acute respiratory infection from
      mothers' interviews. Regardless of the amount of vitamin A-rich foods consumed,
      children who were regularly supplemented with high doses of vitamin A were
      protected against malnutrition, diarrhea, and acute respiratory infection at a
      higher rate than children who were supplemented only once or were never
      supplemented. Regularly providing a high-dose (200,000 IU) capsule of vitamin A
      to children aged 6 to 60 months, including those who eat vitamin A-rich foods,
      may be effective in decreasing the prevalence of morbidity from malnutrition,
      diarrhea, and acute respiratory infection.

PMID- 15460269
TI  - Consumption of vitamin A by breastfeeding children in rural Kenya.
AB  - Vitamin A deficiency remains a significant health risk in developing countries,
      affecting infants and children in particular. To counter child malnutrition,
      mothers are encouraged to breastfeed to ensure that their children receive
      adequate macro- and micronutrients, including vitamin A. However, this assumes
      that the mother has sufficient vitamin A intake to provide enough vitamin A to
      her child. This study investigates maternal and infant intakes of locally
      available foods of high vitamin A content in a rural agricultural community in
      Kenya. The study aims to establish the community risk for vitamin A deficiency
      and to assess whether breast milk is adequate to maintain and build retinol
      reserves of the breastfed infant. The study assesses 62 mother-child pairs and
      employs several methods to support its objectives, including the Helen Keller
      International food-frequency survey, maternal and infant anthropometric
      measurements, and maternal breast-milk and blood samples to determine breast-milk
      and serum retinol levels. We found that mothers with marginal (< 0.700
      micromol/l) serum retinol and breast-milk deficient (< 1.05 micromol/l) in
      retinol accounted for 45.2% and 77.4%, of our sample, respectively. A significant
      (p < 0.05) proportion (40.3%) of mothers had breast milk deficient in retinol and
      marginal levels of serum retinol. The risk of vitamin A deficiency in breastfed
      infants older than six months was high, because 89.5% of them did not consume
      foods high in vitamin A content three times weekly. The primary source of vitamin
      A for infants younger than six months was breast-milk deficient in retinol
      vitamin A. This study suggests that in this rural community, breastfed infants
      may not receive appropriate foods with high vitamin A content and that although
      exclusive breastfeeding is advocated, most breast milk is deficient in retinol,
      further heightening the risk of vitamin A deficiency.

PMID- 15460270
TI  - Stability of salt double-fortified with ferrous fumarate and potassium iodate or
      iodide under storage and distribution conditions in Kenya.
AB  - The stability of table salt double-fortified with iron as ferrous fumarate, and
      with iodine as potassium iodide or potassium iodate, has been investigated under
      actual field conditions of storage and distribution in the coastal and highland
      regions of Kenya. Seven 200-g sample packets of double-fortified salt in sealed
      polyethylene bags and a similar packet containing a datalogger for monitoring
      temperature and humidity were packaged with 21 sample bags of salt from another
      study into a bundle, which then entered the distribution network from a salt
      manufacturer's facility to the consumer. Iodine retention values of up to 90% or
      more were obtained during the three-month study. Double-fortified salt was
      prepared using ferrous fumarate microencapsulated with a combination of binders
      and coloring agents and coated with soy stearine, in combination with either
      iodated salt or salt iodized with potassium iodide microencapsulated with dextrin
      and coated with soy stearine. Most of the ferrous iron was retained, with less
      than 17% being oxidized to the ferric state. The polyethylene film overwrap of
      salt packs in the bundles provided significant protection from ambient humidity.
      Salt double-fortified with iodine and microencapsulated iron ferrous fumarate
      premix was generally quite stable, because both iodine and ferrous iron were
      protected during distribution and retail in typical tropical conditions in
      Kenya's highlands and humid lowlands.

PMID- 15460271
TI  - Rethinking food aid to fight AIDS.
AB  - While the realization that AIDS is far more than a health problem has dawned only
      recently, many development organizations have yet to undertake thorough analyses
      of what this means for what they do, and how they do it. Even fewer have actually
      changed their policies and procedures to adjust to these new realities. We know
      that food and nutrition are fundamentally intertwined with HIV transmission and
      the impacts of AIDS. Food and nutrition security is fundamentally relevant to all
      four of the conventional pillars of HIV/AIDS response-prevention, care,
      treatment, and mitigation-and food aid can be an important weapon in the arsenal.
      This paper, based on a detailed review of the relevant literature and the
      findings of a mission to eastern and southern Africa, highlights the implications
      of the HIV/AIDS pandemic for food aid strategy and programming. By viewing food
      aid programs through an "HIV/AIDS lens" and in the context of a livelihoods
      approach, the authors argue that organizations can effectively design
      interventions that reduce both susceptibility to HIV and vulnerability to AIDS
      impacts. Though there is little empirical evidence regarding the effectiveness of
      food aid in responding to HIV/AIDS, the authors argue that this should not
      constrain action. Using past experience as a guide, organizations can learn by
      doing, documenting, and continually reassessing their programs using the evolving
      lens, so as to ensure maximal relevance and impact.

PMID- 15460272
TI  - HIV/AIDS and humanitarian action.

PMID- 15460273
TI  - Prevalence of overweight and obesity among high-school girls in Tabriz, Iran, in
      2001.
AB  - Overweight and obesity are among the most prevalent nutritional problems in
      developed and developing countries. In this descriptive study, we attempted to
      determine the prevalence of overweight and obesity in Iranian adolescent girls
      attending high school in Tabriz. A sample of 1,650 (final study group, 1,518)
      high-school girls aged 14 to 20 years was selected by stepwise random sampling
      from five districts of Tabriz. Overweight and obesity were defined according to
      body mass index (BMI) percentiles from the First National Health and Nutrition
      Examination Survey (NHANES I) and the International Obesity Task Force (IOTF) BMI
      cutoffs. According to the NHANES I criteria, 14.6% of the study subjects were
      overweight or obese. Overweight and obesity was seen in 11. 1% and 3.6% of the
      students, respectively. By the IOTF cutoffs, 14% of the subjects were overweight
      or obese. Overweight and obesity were seen in 10.1% and 3.9% of the students,
      respectively. Of the study subjects, 8% had a BMI below the 15th percentile of
      NHANES I, an indicator of underweight. The prevalence of overweight and obesity
      in Tabriz high-school girls is higher than in many, but not all, parts of Iran,
      but lower than in some neighboring countries such as Saudi Arabia. In this age
      group, in addition to overweight and obesity, underweight (BMI < or = 15th
      percentile) is also present.

PMID- 15460274
TI  - WHO global strategy on diet, physical activity and health.

PMID- 15460275
TI  - In response to Piwoz et al. "Promotion and advocacy for improved complementary
      feeding: can we apply the lessons learned from breastfeeding?".

PMID- 15460276
TI  - From WHO: new HIV and infant-feeding tools.

PMID- 15460277
TI  - Learning to detect natural image boundaries using local brightness, color, and
      texture cues.
AB  - The goal of this work is to accurately detect and localize boundaries in natural
      scenes using local image measurements. We formulate features that respond to
      characteristic changes in brightness, color, and texture associated with natural
      boundaries. In order to combine the information from these features in an optimal
      way, we train a classifier using human labeled images as ground truth. The output
      of this classifier provides the posterior probability of a boundary at each image
      location and orientation. We present precision-recall curves showing that the
      resulting detector significantly outperforms existing approaches. Our two main
      results are 1) that cue combination can be performed adequately with a simple
      linear model and 2) that a proper, explicit treatment of texture is required to
      detect boundaries in natural images.

PMID- 15460278
TI  - Recognition of shapes by editing their shock graphs.
AB  - This paper presents a novel framework for the recognition of objects based on
      their silhouettes. The main idea is to measure the distance between two shapes as
      the minimum extent of deformation necessary for one shape to match the other.
      Since the space of deformations is very high-dimensional, three steps are taken
      to make the search practical: 1) define an equivalence class for shapes based on
      shock-graph topology, 2) define an equivalence class for deformation paths based
      on shock-graph transitions, and 3) avoid complexity-increasing deformation paths
      by moving toward shock-graph degeneracy. Despite these steps, which tremendously
      reduce the search requirement, there still remain numerous deformation paths to
      consider. To that end, we employ an edit-distance algorithm for shock graphs that
      finds the optimal deformation path in polynomial time. The proposed approach
      gives intuitive correspondences for a variety of shapes and is robust in the
      presence of a wide range of visual transformations. The recognition rates on two
      distinct databases of 99 and 216 shapes each indicate highly successful within
      category matches (100 percent in top three matches), which render the framework
      potentially usable in a range of shape-based recognition applications.

PMID- 15460279
TI  - Gabor-based kernel PCA with fractional power polynomial models for face
      recognition.
AB  - This paper presents a novel Gabor-based kernel Principal Component Analysis (PCA)
      method by integrating the Gabor wavelet representation of face images and the
      kernel PCA method for face recognition. Gabor wavelets first derive desirable
      facial features characterized by spatial frequency, spatial locality, and
      orientation selectivity to cope with the variations due to illumination and
      facial expression changes. The kernel PCA method is then extended to include
      fractional power polynomial models for enhanced face recognition performance. A
      fractional power polynomial, however, does not necessarily define a kernel
      function, as it might not define a positive semidefinite Gram matrix. Note that
      the sigmoid kernels, one of the three classes of widely used kernel functions
      (polynomial kernels, Gaussian kernels, and sigmoid kernels), do not actually
      define a positive semidefinite Gram matrix either. Nevertheless, the sigmoid
      kernels have been successfully used in practice, such as in building support
      vector machines. In order to derive real kernel PCA features, we apply only those
      kernel PCA eigenvectors that are associated with positive eigenvalues. The
      feasibility of the Gabor-based kernel PCA method with fractional power polynomial
      models has been successfully tested on both frontal and pose-angled face
      recognition, using two data sets from the FERET database and the CMU PIE
      database, respectively. The FERET data set contains 600 frontal face images of
      200 subjects, while the PIE data set consists of 680 images across five poses
      (left and right profiles, left and right half profiles, and frontal view) with
      two different facial expressions (neutral and smiling) of 68 subjects. The
      effectiveness of the Gabor-based kernel PCA method with fractional power
      polynomial models is shown in terms of both absolute performance indices and
      comparative performance against the PCA method, the kernel PCA method with
      polynomial kernels, the kernel PCA method with fractional power polynomial
      models, the Gabor wavelet-based PCA method, and the Gabor wavelet-based kernel
      PCA method with polynomial kernels.

PMID- 15460280
TI  - Algorithms for matching 3D line sets.
AB  - Matching two sets of lines is a basic tool that has applications in many computer
      vision problems such as scene registration, object recognition, motion
      estimation, and others. Line sets may be composed of infinitely long lines or
      finite length line segments. Depending on line lengths, three basic cases arise
      in matching sets of lines: 1) finite-finite, 2) finite-infinite, and 3) infinite
      infinite. Case 2 has not been treated in the literature. For Cases 1 and 3,
      existing algorithms for matching 3D line sets are not completely satisfactory in
      that they either solve special situations, or give approximate solutions, or may
      not converge, or are not invariant with respect to coordinate system transforms.
      In this paper, we present new algorithms that solve exactly all three cases for
      the general situation. The algorithms are provably convergent and invariant to
      coordinate transforms. Experiments with synthetic and real 3D image data are
      reported.

PMID- 15460281
TI  - First order augmentation to tensor voting for boundary inference and multiscale
      analysis in 3D.
AB  - Most computer vision applications require the reliable detection of boundaries.
      In the presence of outliers, missing data, orientation discontinuities, and
      occlusion, this problem is particularly challenging. We propose to address it by
      complementing the tensor voting framework, which was limited to second order
      properties, with first order representation and voting. First order voting fields
      and a mechanism to vote for 3D surface and volume boundaries and curve endpoints
      in 3D are defined. Boundary inference is also useful for a second difficult
      problem in grouping, namely, automatic scale selection. We propose an algorithm
      that automatically infers the smallest scale that can preserve the finest
      details. Our algorithm then proceeds with progressively larger scales to ensure
      continuity where it has not been achieved. Therefore, the proposed approach does
      not oversmooth features or delay the handling of boundaries and discontinuities
      until model misfit occurs. The interaction of smooth features, boundaries, and
      outliers is accommodated by the unified representation, making possible the
      perceptual organization of data in curves, surfaces, volumes, and their
      boundaries simultaneously. We present results on a variety of data sets to show
      the efficacy of the improved formalism.

PMID- 15460282
TI  - Top-down induction of model trees with regression and splitting nodes.
AB  - Model trees are an extension of regression trees that associate leaves with
      multiple regression models. In this paper, a method for the data-driven
      construction of model trees is presented, namely, the Stepwise Model Tree
      Induction (SMOTI) method. Its main characteristic is the induction of trees with
      two types of nodes: regression nodes, which perform only straight-line
      regression, and splitting nodes, which partition the feature space. The multiple
      linear model associated with each leaf is then built stepwise by combining
      straight-line regressions reported along the path from the root to the leaf. In
      this way, internal regression nodes contribute to the definition of multiple
      models and have a "global" effect, while straight-line regressions at leaves have
      only "local" effects. Experimental results on artificially generated data sets
      show that SMOTI outperforms two model tree induction systems, M5' and RETIS, in
      accuracy. Results on benchmark data sets used for studies on both regression and
      model trees show that SMOTI performs better than RETIS in accuracy, while it is
      not possible to draw statistically significant conclusions on the comparison with
      M5'. Model trees induced by SMOTI are generally simple and easily interpretable
      and their analysis often reveals interesting patterns.

PMID- 15460283
TI  - A statistical model for contours in images.
AB  - In this paper, we describe a statistical model for the gradient vector field of
      the gray level in images validated by different experiments. Moreover, we present
      a global constrained Markov model for contours in images that uses this
      statistical model for the likelihood. Our model is amenable to an Iterative
      Conditional Estimation (ICE) procedure for the estimation of the parameters; our
      model also allows segmentation by means of the Simulated Annealing (SA)
      algorithm, the Iterated Conditional Modes (ICM) algorithm, or the Modes of
      Posterior Marginals (MPM) Monte Carlo (MC) algorithm. This yields an original
      unsupervised statistical method for edge-detection, with three variants. The
      estimation and the segmentation procedures have been tested on a total of 160
      images. Those tests indicate that the model and its estimation are valid for
      applications that require an energy term based on the log-likelihood ratio.
      Besides edge-detection, our model can be used for semiautomatic extraction of
      contours, localization of shapes, non-photo-realistic rendering; more generally,
      it might be useful in various problems that require a statistical likelihood for
      contours.

PMID- 15460284
TI  - Separation of diffuse and specular components of surface reflection by use of
      polarization and statistical analysis of images.
AB  - The image of an opaque object is created by observing the reflection of the light
      incident on its surface. The dichromatic reflection model describes the surface
      reflection as the sum of two components, diffuse and specular terms. The specular
      reflection component is usually strong in its intensity and polarized
      significantly compared to the diffuse components. On the other hand, the
      intensity of the diffuse component is weak and it tends to be unpolarized except
      near occluding contours. Thus, the observation of an object through a rotating
      polarizer approximately yields images containing constant diffuse component and
      specular component of different intensity. In this paper, we show that diffuse
      and specular components of surface reflection can be separated as two independent
      components when we apply Independent Component Analysis to the images observed
      through a polarizer of different orientations. We give a separation simulation of
      artificial data and also give some separation results of real scenes.

PMID- 15460285
TI  - Invariant fitting of two view geometry.
AB  - This paper describes an extension of Bookstein's and Sampson's methods, for
      fitting conics, to the determination of epipolar geometry, both in the calibrated
      case, where the Essential matrix E is to be determined or in the uncalibrated
      case, where we seek the fundamental matrix F. We desire that the fitting of the
      relation be invariant to Euclidean transformations of the image, and show that
      there is only one suitable normalization of the coefficients and that this
      normalization gives rise to a quadratic form allowing eigenvector methods to be
      used to find E or F, or an arbitrary homography H. The resulting method has the
      advantage that it exhibits the improved stability of previous methods for
      estimating the epipolar geometry, such as the preconditioning method of Hartley,
      while also being invariant to equiform transformations.

PMID- 15460286
TI  - Recursive unsupervised learning of finite mixture models.
AB  - There are two open problems when finite mixture densities are used to model
      multivariate data: the selection of the number of components and the
      initialization. In this paper, we propose an online (recursive) algorithm that
      estimates the parameters of the mixture and that simultaneously selects the
      number of components. The new algorithm starts with a large number of randomly
      initialized components. A prior is used as a bias for maximally structured
      models. A stochastic approximation recursive learning algorithm is proposed to
      search for the maximum a posteriori (MAP) solution and to discard the irrelevant
      components.

PMID- 15460287
TI  - Adaptive quasiconformal kernel nearest neighbor classification.
AB  - Nearest neighbor classification assumes locally constant class conditional
      probabilities. This assumption becomes invalid in high dimensions due to the
      curse-of-dimensionality. Severe bias can be introduced under these conditions
      when using the nearest neighbor rule. We propose an adaptive nearest neighbor
      classification method to try to minimize bias. We use quasiconformal transformed
      kernels to compute neighborhoods over which the class probabilities tend to be
      more homogeneous. As a result, better classification performance can be expected.
      The efficacy of our method is validated and compared against other competing
      techniques using a variety of data sets.

PMID- 15460288
TI  - Optimal linear representations of images for object recognition.
AB  - Although linear representations are frequently used in image analysis, their
      performances are seldom optimal in specific applications. This paper proposes a
      stochastic gradient algorithm for finding optimal linear representations of
      images for use in appearance-based object recognition. Using the nearest neighbor
      classifier, a recognition performance function is specified and linear
      representations that maximize this performance are sought. For solving this
      optimization problem on a Grassmann manifold, a stochastic gradient algorithm
      utilizing intrinsic flows is introduced. Several experimental results are
      presented to demonstrate this algorithm.

PMID- 15460289
TI  - VC-dimension of exterior visibility.
AB  - In this paper, we study the Vapnik-Chervonenkis (VC)-dimension of set systems
      arising in 2D polygonal and 3D polyhedral configurations where a subset consists
      of all points visible from one camera. In the past, it has been shown that the VC
      dimension of planar visibility systems is bounded by 23 if the cameras are
      allowed to be anywhere inside a polygon without holes. Here, we consider the case
      of exterior visibility, where the cameras lie on a constrained area outside the
      polygon and have to observe the entire boundary. We present results for the cases
      of cameras lying on a circle containing a polygon (VC-dimension= 2) or lying
      outside the convex hull of a polygon (VC-dimension= 5). The main result of this
      paper concerns the 3D case: We prove that the VC-dimension is unbounded if the
      cameras lie on a sphere containing the polyhedron, hence the term exterior
      visibility.

PMID- 15460290
TI  - Dietary counseling--time for a nutritionist in the office?

PMID- 15460291
TI  - Dental teachers or dental technicians?

PMID- 15460292
TI  - Clinical success and parental satisfaction with anterior preveneered primary
      stainless steel crowns.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical success of and
      parental satisfaction with treatment using prefabricated resin-faced stainless
      steel crowns (SSCs; Kinder Krowns, Mayclin Dental Studios, Minneapolis, Minn) on
      anterior primary teeth. METHODS: Patients treated with Kinder Krowns within the
      last 3 years were recalled for dinical evaluation and completion of a parental
      satisfaction survey in this retrospective cross-sectional study. Clinical
      evaluation was performed for crown retention, facing retention, and resin veneer
      wear. RESULTS: Forty-six teeth were evaluated in 12 children. The average age of
      the crown at the time of examination was 17.5 months (range 5-38 months). All
      crowns were present in the mouth, and resin fracture resulting in partial or
      total facing loss was seen in 24% of the crowns. No resin facing fracture or
      visible wear was seen in 61% of the crowns. Six crowns had total facing loss from
      fracture (13%), while 5 (11%) had partial facing fracture. Wear (7 crowns, 15%)
      was limited to less than the incisal one third of the crown. The parental
      satisfaction with the preveneered SSCs overall was high, with satisfaction for
      appearance and the shape being the lowest. CONCLUSIONS: Kinder Krown
      prefabricated resin-faced SSCs showed a low failure rate, and the parental
      satisfaction with treatment was positive.

PMID- 15460293
TI  - Relationship between amphetamine ingestion and gingival enlargement.
AB  - PURPOSE: The purpose of this study was to determine the relationship between
      amphetamine ingestion and gingival enlargement. METHODS: A total of 40 subjects
      were included in this study. Group 1 consisted of 20 subjects taking amphetamines
      and attending the dental clinic at Children's Hospital of Buffalo and The
      University at Buffalo School of Dental Medicine. These subjects were not taking
      phenytoin, cyclosporine, or calcium channel blockers. Patients with
      cardiovascular or hormonal disorders were excluded from the study. The
      information obtained from patients' parents or legal guardians were: (1) the time
      when the patient started taking the medication; (2) how often the patient took
      the medication per day; and (3) the medication's dosage. Gingival and plaque
      indices were also measured to assess gingival health. The Silness and Loe plaque
      index and modified gingival index were used. A second group of 20 healthy
      subjects not taking any medications was used as a control group. Gingival
      enlargement was evaluated clinically by one examiner and evaluated from intraoral
      photographs by another examiner. RESULTS: The results of this study demonstrated
      a relationship between amphetamine usage and gingival enlargement. There was a
      statistically significant increased prevalence (P<.05) of gingival enlargement in
      the group of patients taking amphetamines. CONCLUSIONS: This study shows that
      patients taking amphetamines have an increased risk of gingival enlargement. A
      stringent effort to minimize gingival inflammation should be instituted, and
      patients should be monitored closely with more follow-up appointments than
      nonmedicated patients.

PMID- 15460294
TI  - Evidence-based assessment: evaluation of the formocresol versus ferric sulfate
      primary molar pulpotomy.
AB  - PURPOSE: Formocresol and ferric sulfate were evaluated as pulpotomy medicaments
      using evidence-based dentistry principles. Formocresol has been challenged as a
      potential carcinogen and mutagen, leading to consideration of ferric sulfate.
      METHODS: The PICOT statement was: (P) In human carious primary molars with
      reversible coronal pulpitis, (I) does a pulpotomy performed with ferric sulfate,
      (C) compared with formocresol, (O) result in dinical/radiographic success, (T) in
      time periods up to exfoliation? Relevant papers (N=894) were identified from
      databases and inclusion criteria were applied; 94 papers remained (randomized
      clinical trials [RCTs]=7; clinical trials [CTs]=28; case-control studies=14;
      opinions, cohort, and cross-sectional studies=4; reviews=22; irretrievable
      papers=19). Three RCTs and 10 CTs (total teeth: formocresol=753; ferric
      sulfate=90) were meta-analyzed; 1 RCT and 1 CT were tested for homogeneity (odds
      ratios; 95% confidence intervals); 3 RCTs and 10 CTs were examined by student's t
      test. RESULTS: Clinical data indicated ferric sulfate was significantly more
      successful than formocresol (OR=1.95; CI=1.01-3.80). Radiographic data indicated
      no difference between medicaments (OR=0.90; CI=0.58-1.39). Medicaments did not
      differ with t-tests of clinical (P>.10) and radiographic (P>.50) data.
      CONCLUSIONS: This evidence-based assessment concluded that, in human carious
      primary molars with reversible coronal pulpitis, pulpotomies performed with
      either formocresol or ferric sulfate are likely to have similar
      clinical/radiographic success.

PMID- 15460295
TI  - Nitrous oxide concentrations in the posterior nasopharynx during administration
      by nasal mask.
AB  - PURPOSE: Nitrous oxide (N2O) administration with nasal mask produces variable
      outcomes in dental patients. This study describes a novel sampling method to
      measure actual inspired/expired N2O concentrations ([N2O]). METHODS: Fifteen
      adult volunteers (32.5 +/- 8.5 years) underwent placement of a nasopharyngeal
      probe. With a nasal mask, 100% oxygen (O2) was administered for 2 minutes. N2O
      was introduced incrementally every 2 minutes for a final flowmeter [N2O] of 50%
      and subsequently decreased in the same manner. Anesthesia gas monitors analyzed
      inspired/expired [N2O], [O2], and PETCO2 from the nasopharynx and end
      inspired/expired [N2O] in the mask. Data were measured every 20 seconds and
      analyzed. Inspired/expired nasopharyngeal and nasal mask [N2O] and [O2] were
      expressed as the median value at each time point for all subjects and plotted
      against flowmeter settings. RESULTS: Average inspired nasal mask [N2O] was 31%
      lower than flowmeter settings and decreased by another 19% on the way to the
      nasopharyngeal sampling site. During the phase of increasing N2O, average expired
      nasopharyngeal [N2O] was 22% lower than inspired [N2O]. When N2O was decreased,
      the effect was reversed and average expired [N2O] was 18% higher than inspired.
      Expired [N2O] was on average 51% lower than flowmeter settings. Mean PETCO2 was
      39.7 +/- 1.4 mm Hg. CONCLUSIONS: Nasopharyngeal end-expired [N2O] varied markedly
      from flowmeter settings. Correlation of PETCO2 with expected physiologic values
      validates sampling methodology. This method allows accurate, continuous, and
      actual measurements of inhaled/exhaled gases in awake patients as well as
      decision-making/analysis of effectiveness of mask type to determine average [N2O]
      during administration by nasal mask.

PMID- 15460296
TI  - Custom sports mouthguard modified for orthodontic patients and children in the
      transitional dentition.
AB  - Young athletes with ever-changing transitional dentitions and those wearing fixed
      orthodontic appliances can benefit from custom-formed protective mouthguards.
      Modifications of the traditional vacuum-forming method are useful to fabricate
      mouthguards for such patients and extend the useful life of these devices. The
      purpose of this case report is to document fabrication of custom-formed
      protective mouthguards for a 10-year-old boy wearing fixed orthodontic appliances
      and a 9-year-old girl with a fixed palatal expander in place.

PMID- 15460297
TI  - A novel multidisciplinary approach for the treatment of an intruded immature
      permanent incisor.
AB  - The optimal treatment for intruded permanent teeth has not yet been determined.
      The ideal treatment option is the one with the lowest probability of developing
      complications such as external root resorption and marginal bone loss. Each case
      should be considered individually, bearing in mind the severity of the intrusion,
      the stage of root development, and tooth mobility. Management of an intruded
      permanent tooth may consist of: (1) observation for spontaneous eruption; (2)
      surgical crown uncovering; (3) orthodontic extrusion (with or without prior
      luxation of the intruded tooth); (4) and partial surgical extrusion, immediately
      followed by orthodontic extrusion and surgical repositioning. The purpose of this
      article was to review the treatment options for intruded immature permanent
      incisors, and to present a new modality of an elective internal strengthening of
      the immature root weakened by external root resorption. A case of an intrusive
      luxation injury in a 7 1/2-year-old child and the resulting complications
      utilizing this technique is described. This is the first known report in the
      pediatric dentistry literature of performing an elective (preventive) internal
      strengthening of an immature root weakened by severe external inflammatory
      resorption. The child was followed for 5 years with an excellent clinical
      outcome. This technique should be considered for treatment of immature permanent
      teeth with thin cervical root dentin and external or internal root resorption due
      to trauma or caries.

PMID- 15460298
TI  - Occlusal sealant success over ten years in a private practice: comparing
      longevity of sealants placed by dentists, hygienists, and assistants.
AB  - PURPOSE: The purpose of this 10-year, retrospective, cohort study was to evaluate
      the success of permanent molar sealants by comparing the effectiveness of
      sealants placed by dentists, dental hygienists, and dental assistants in a
      private dental practice, with all operators using an identical, standardized,
      application technique and 4-handed dentistry. METHODS: From 810 patient records
      that met entry criteria, the long-term follow-up records of 3,194 permanent first
      molars were evaluated. Data were collected and evaluated by survival analyses
      methods for: (1) time to first failure (caries or restoration of the sealed
      surface); (2) fluoride history; (3) caries experience; (4) operator type; (5)
      behavior at sealant placement; (6) tooth type; (7) age at placement; and (8)
      patient gender. RESULTS: Cumulative survival probability for 10 years in this
      practice was 87%, using Kaplan Meier analyses. The factors associated with an
      increased risk of failure included: (1) age (P<.001); (2) dmft (P<.003); (3) no
      fluoride (P<.001); (4) dentist (P<.001); and (5) registered dental assistant
      (P<.001). While all operator groups had success rates equal to or exceeding
      previous studies, dentists and registered dental assistants showed 3 times and 2
      times the risk of failure, respectively, compared to the registered dental
      hygienists. The no-fluoride group showed almost twice the risk of failure as
      compared to the optimal fluoride group. Behavior showed a slightly higher risk of
      failure that approached significance. Age and dmft were highly significant, with
      slight increased risk of failure. Supplemental fluoride showed a protective
      effect, but this was marginally significant. Gender and tooth-type were not
      significant in this model. Major variations in success rates were observed in the
      dental assistant group, with 2 individuals accounting for most of the failures.
      CONCLUSIONS: This study supports delegation of sealant delivery to auxiliaries,
      since dental assistants and dental hygienists were equal to or better than the
      dentists in long-term sealant effectiveness.

PMID- 15460299
TI  - Accuracy of familial reporting of a child's medical history in a dental clinic
      setting.
AB  - PURPOSE: Accurate reporting of medical history information is essential to
      provide safe and successful dental treatment to children. The purpose of this
      study was to evaluate the accuracy of health histories reported by
      parents/guardians of pediatric patients presenting for dental treatment by
      comparing them to the histories provided in the child's medical chart. METHODS:
      Data collection from the dental record was performed using the medical history
      questionnaire from the child's first visit as the data source. Data collected
      focused on knowledge of the child's medical conditions, current medications,
      allergies, immunization status, and need for prophylactic antibiotics.
      Corresponding data were collected from the child's medical chart. Statistical
      analysis included kappa analysis and calculation of sensitivity, specificity, and
      failure-to-report rates. RESULTS: The study group consisted of 226 children (99
      girls, 127 boys), with a mean age of 10.35 years. The patients were divided into
      2 groups based on their medical status (healthy vs medically compromised). For
      the medically compromised children, parents had high sensitivity reporting rates
      (>75% sensitivity) for only 2 out of the 9 medical categories. For both groups,
      <50% of the medicine, allergy, and need for prophylaxis categories had
      sensitivity rates above 75%. Failure-to-report rates of 40% to 60% were common,
      with some as high as 80%. Weighted failure-to-report rates were consistently
      higher for medically compromised children compared to healthy children.
      CONCLUSIONS: Parents/guardians of children presenting for dental treatment are
      not always able to accurately report vital medical history information.
      Therefore, pediatric dentists need to more closely examine the dental health
      questionnaire and make every attempt to obtain accurate information to provide
      appropriate care for each patient.

PMID- 15460300
TI  - Rural versus urban analysis of dental procedures provided to Virginia Medicaid
      recipients.
AB  - PURPOSE: The purpose of this study was to report the distribution of procedures
      provided to Virginia Medicaid children by 3 types of dental providers in rural
      and urban areas. METHODS: Medicaid claims filed for dental patients less than 21
      years old were obtained and analyzed for fiscal years 1994-1995. Dental providers
      were categorized according to their practice type: (1) general practice (GP); (2)
      pediatric (PD); and (3) public health (PH) dentists. Each type of practice was
      categorized as practicing in a metropolitan, urban, rural, or completely rural
      location and evaluated for percentages of preventive, diagnostic, and corrective
      services provided. RESULTS: Rural areas had a higher percentage of significant
      providers than did metropolitan or urban areas. General dentists performed more
      diagnostic and preventive but fewer corrective procedures than pediatric
      dentists. Pediatric dentists and general dentists in completely rural areas
      performed more corrective procedures than their counterparts in metropolitan or
      urban areas. CONCLUSIONS: General, pediatric, and public health dentists in
      metropolitan and urban areas perform slightly more diagnostic services and fewer
      corrective services than practitioners in more rural areas.

PMID- 15460301
TI  - Assessment of pain by the child, dentist, and independent observers.
AB  - PURPOSE: The objective of this study was to analyze the assessment of pain and
      distress by the child, dentist, and independent observers during a dental
      injection and study the relationship between the different assessments. METHODS:
      The amount of pain experienced by the child during local anesthesia was reported
      independently by the child to both the dentist and parent on a 4-point scale
      running from "no pain" to "a lot of pain." The dentist and observers also gave a
      score for the pain experienced on a 4-point scale. The amount of distress
      experienced by the child during local anesthesia was assessed by the dentist and
      observers using a 6-point scale (from "relaxed" to "out of contact"). RESULTS:
      The dentists' pain assessment was the lowest. A substantial correlation was found
      between the child's self-reported pain and the pain as assessed by independent
      observers. There was a moderate correlation between the amount of distress and
      pain intensity as reported by the child during the anesthesia phase. CONCLUSIONS:
      Observation of a child in a videotaped procedure is apparently the most reliable
      method to accurately assess pain behavior and to discriminate pain from distress.
      A combination of the child's report and video observation is advised to assess
      pain in young children.

PMID- 15460302
TI  - Supernumerary premolars: a literature review.
AB  - Supernumerary premolars appear to be more common than previously estimated. The
      purpose of this report was to review most of the cases published in the dental
      literature since 1932. The authors found that supernumerary premolars occur 3
      times more in males than in females, indicating a possible sex-linked
      inheritance, with the highest frequency of occurrence in the mandibular premolar
      region (74%). They are also the most common supernumerary teeth in the mandibular
      arch (7%), and their incidence is 1% (1 in 157)-much higher than previously
      reported. Maxillary supernumerary premolars were found to occur at a lower rate
      (26%). The possible mechanisms of development are described, with a localized
      hyperactivity of the dental lamina being the most widely accepted theory.
      Recurrence of supernumerary premolars after being surgically removed has been
      reported in 8% of the cases reviewed. Patients with a previous history of
      anterior conical or tuberculated supernumerary teeth at an early age have a 24%
      possibility of developing single or multiple supernumerary premolars at a later
      age. Early diagnosis and appropriate follow-up with panoramic radiographs is
      extremely important. Various treatment recommendations are also discussed.

PMID- 15460303
TI  - Diet counseling during the infant oral health visit.
AB  - Diet counseling is an integral part of anticipatory guidance during the infant
      oral health visit. Similar to dietary instructions for children of all ages, the
      primary emphasis is on sugar intake frequency. There are, however, other infant
      specific dietary issues that must also be addressed during the infant oral health
      visit. Breast-feeding should be promoted during the first year of life, although
      ad libitum nocturnal breast-feeding should be discouraged after the first primary
      tooth erupts. Bottle-fed infants should not be put to sleep with the bottle.
      Weaning from the breast or the bottle should be encouraged by 12 to 14 months of
      age. Infants older than 6 months and with exposure to less than 0.3 ppm fluoride
      in their drinking water need dietary fluoride supplements of 0.25 mg fluoride per
      day. Only 4 to 6 oz of fruit juice should be consumed by infants per day. Infants
      should not be given powdered beverages or soda pop, as these drinks pose
      increased risk for dental caries. Iron-fortified infant cereals, along with
      breast milk or infant formula, should be consumed by infants who are at least 6
      months of age. Cow's milk should be completely avoided in the first year of life
      and restricted to less than 24 oz per day in the second year of life. Parents
      should be cautioned regarding the potential of various foods to constitute a
      choking hazard for infants.

PMID- 15460304
TI  - If you're not coding, you're not billing. The world of codes and HIM alike
      represents a fast-moving landscape.

PMID- 15460305
TI  - Going global. AHIMA convention offers international perspective on health
      information management, along with the hottest HIM issues of the day.

PMID- 15460306
TI  - Revolutionizing radiology with images on demand. Three SANs and a PACS provide
      Colorado healthcare system physicians with easy access to radiological images, as
      well as quick disaster recovery.

PMID- 15460307
TI  - The HIPAA prescription for healthcare--why isn't it working?

PMID- 15460308
TI  - Lasting impressions. Distributed printing helps southern IDN streamline process
      and save dollars.

PMID- 15460309
TI  - Nurses feel right at home with healthcare. Notebook PC makes patient visits easy
      for Alabama home health agency nurses.

PMID- 15460310
TI  - Creating a health-conscious community. Montana health system uses interactive
      customer relationship management strategies to increase women's participation in
      heart disease program.

PMID- 15460311
TI  - The health plan as a change agent. Aetna uses EBM, data analysis and a moderated,
      personal touch to effect changes and improvements in physicians' treatment plans.

PMID- 15460312
TI  - Pursuing perfection. Minnesota healthcare organization uses EBM and process re
      engineering to successfully apply best practices to the treatment of depression.

PMID- 15460313
TI  - Smarter surgical decisions supported by data. Mississippi hospital uses IT to
      gets its arms around surgical scheduling, inventory control, documentation and
      staff utilization.

PMID- 15460314
TI  - Keys to successful CPOE implementation. Connecticut hospital maintains a constant
      focus on improved patient safety as its top reason for implementing CPOE.

PMID- 15460315
TI  - Building in for access and usability. North Carolina health system achieves
      multiple data access and report management goals with IT.

PMID- 15460316
TI  - Making the EMR user-friendly enough to use.

PMID- 15460317
TI  - Real-time reverse transcription-polymerase chain reaction assays for the
      detection and differentiation of North American swine influenza viruses.
AB  - Swine influenza is an acute respiratory disease of swine caused by type A
      influenza viruses. Before 1998, mainly "classical" HIN1 swine influenza viruses
      (SIVs) were isolated from swine in the United States. Since then, antigenically
      distinct reassortant H3 and H1 SIVs have been identified as causative agents of
      respiratory disease in pigs on US farms. Improvement in SIV diagnostics is needed
      in light of the recently observed rapid evolution of H1 and H3 SIVs and their
      zoonotic potential. To address this need, real-time reverse transcription
      polymerase chain reaction (RT-PCR) assays for the detection of SIVs were
      developed. A highly sensitive matrix (M) gene-based RT-PCR assay that is able to
      detect both the H1 and H3 subtypes of SIVs, with a sensitivity per reaction of
      approximately 2 copies of in vitro-generated M-specific negative-sense RNA
      molecules and approximately 0.05 TCID50 in lung lavage of experimentally SIV
      infected pigs, was established. This RT-PCR assay can be performed within a few
      hours and showed a sensitivity of 94% and a specificity of 85% when compared with
      virus isolation. In addition, H1-, H3-, N1-, and N2-specific primer and probe
      sets were designed for use in the differentiation of different SIV subtypes. The
      hemagglutinin (H)- and neuraminidase (N)-specific primer and probe sets were less
      sensitive than the M-specific assay, although they were found to be specific for
      their respective viral genes and able to distinguish between their respective SIV
      subtypes.

PMID- 15460318
TI  - Characterization of a wild-type strain of Francisella tularensis isolated from a
      cat.
AB  - Francisella tularensis type A is the primary cause of tularemia in animals and
      humans in North America. The majority of research on F. tularensis has been done
      with the attenuated live vaccine strain (LVS), which is a type B, but very few
      wild-type F. tularensis strains have been characterized. A gram-negative
      coccobacillus that was isolated in pure culture from the lungs of a cat that died
      after being lost for 5 days was received for identification at the Virginia
      Maryland Regional College of Veterinary Medicine Teaching hospital. The isolate
      (strain TI0902) was not identified (or was misidentified) by commercial
      identification systems; however, it was identified as F. tularensis subspecies
      tularensis (type A) by sequencing a portion of the 16S ribosomal RNA gene.
      Furthermore, repetitive extragenic palindromic sequences-polymerase chain
      reaction amplified a 4-kb DNA fragment from TI0902 that was characteristic of F.
      tularensis type A but not type B. The electrophoretic profile of the
      lipopolysaccharide of strain TI0902 was identical to that of the LVS by Western
      blotting with antiserum to LVS. The protein-enriched outer membrane of strain
      TI0902 contained 6-8 proteins, which were similar in molecular size to those from
      the LVS. Electron microscopy of negatively stained and alcian blue-stained LVS
      and TI0902 cells showed that both strains were coccobacillary in shape and may be
      encapsulated. However, after mouse challenge, the TI0902 strain was clearly more
      virulent than the LVS strain. Results of this study indicate that the genotype
      and phenotype of wild-type F. tularensis type A strain TI0902 is similar, but not
      identical, to that of the LVS strain. Further studies will help determine whether
      pathogenesis and host-pathogen interactions are also similar between the 2
      strains.

PMID- 15460319
TI  - Influence of age and production type on liver copper concentrations in calves.
AB  - A retrospective study of necropsy reports was undertaken to assess the relation
      between liver copper concentration and age, sex, and production class for calves
      that did not have a history compatible with copper toxicosis or with copper
      deficiency. Results of a generalized least squares regression analysis of 601
      records found that copper concentration was as much as 60 mg/kg wet weight higher
      for dairy calves than for beef calves (P < 0.00001, R2 = 0.172). For both beef
      and dairy calves, copper concentration also was significantly associated with
      linear (P = 0.001) and nonlinear (age2, P = 0.002; age3, P = 0.008) functions of
      age, where the concentration increased for the first 2 months, then declined
      until 9 months of age, after which it began to increase. Sex was not associated
      with copper concentration (P = 0.22). The 95% confidence intervals of the mean
      concentration for a group of calves and the 95% prediction intervals of a single
      concentration value for an individual animal are presented. As a consequence of
      the significant influence of both production class (dairy or beef) and age on
      liver copper concentration of calves with no evidence of copper toxicosis or
      copper deficiency, diagnosis of copper imbalances based on liver copper
      concentration in calves should consider the diagnostic covariates of age and
      production class.

PMID- 15460320
TI  - Distribution of viral antigen and tissue lesions in persistent and acute
      infection with the homologous strain of noncytopathic bovine viral diarrhea
      virus.
AB  - Viral distribution and lesions were compared between calves born with persistent
      infection (PI) and calves acutely infected with the same bovine viral diarrhea
      virus (BVDV) isolate. Two PI calves from 1 dairy herd were necropsied. The PI
      viruses from these calves were isolated, characterized by sequencing, and found
      to be identical. This virus strain, designated BVDV2-RS886, was characterized as
      a noncytopathic (ncp) type 2 BVDV. To establish acute infections, BVDV2-RS886 was
      used to inoculate clinically healthy, seronegative calves which were 3 weeks to 3
      months old. Nine calves received 10(6)-10(7) tissue culture infective dose of
      BVDV2-RS886 intranasally. Four additional age-matched animals served as
      noninfected controls. Infected calves were necropsied at 3, 6, 9, or 13 days
      postinoculation (dpi). Viral antigen was detected by immunohistochemistry in
      frozen sections, and lesions were evaluated in hematoxylin eosin-stained
      paraplast sections. In the PI calves, a wide distribution of viral antigen was
      found in all tissues and was not associated with lesions. In the acutely infected
      calves, viral antigen was widespread in lymphoid tissues at 6 dpi but had been
      mostly eliminated at 9 and 13 dpi. Depletion of lymphoid tissues was seen at 6,
      9, and 13 dpi and repopulation at 9 and 13 dpi. In 1 of the calves at 13 dpi,
      severe arteritis was present in lymph nodes and myocardium. This comparison shows
      that an ncp BVDV strain that causes no lesions in PI animals is able to induce
      marked depletion of lymphoid tissues in calves with acute infection. Therefore,
      the failure to eliminate PI cattle from a herd causes problems not only in
      pregnant cattle but may also affect other age groups.

PMID- 15460321
TI  - Mycoplasma otitis in California calves.
AB  - A retrospective study of Mycoplasma otitis in California calves submitted for
      necropsy between 1993 and 2002 was conducted to characterize the demographic
      features of the disease and the pathologic findings associated with infection.
      Sixty-one confirmed cases of Mycoplasma otitis were identified among 20,525
      necropsied cattle. All affected animals were calves, ranging in age from 2 weeks
      to 4 months and with a median age of 1.5 months. Ninety-two percent of the cases
      were dairy breeds. A higher percent of necropsied calves with Mycoplasma otitis
      were males (0.45%) than females (0.23%). The proportion of cases that had
      Mycoplasma otitis increased from 1993 to 2002, and there was a significant (P <
      0.05) seasonal distribution, with the highest proportion in the spring and the
      lowest in the summer months. Infections involved both the middle and inner ear
      and were characterized by a suppurative inflammatory response with extensive bony
      involvement. Three species of Mycoplasma were isolated from the ears: M. bovis,
      M. bovirhinis, and M. alkalescens. Concurrent pneumonia occurred in 47 cases
      (77%), and Mycoplasma was isolated from the lungs of 30 of those cases. The
      increasing proportion of Mycoplasma otitis cases in the past 10 years emphasizes
      the importance of identifying risk factors that could be modified to lower the
      incidence of this disease in calves.

PMID- 15460322
TI  - The pathology of peracute experimental Clostridium perfringens type D
      enterotoxemia in sheep.
AB  - The pathological findings in sheep with peracute experimental Clostridium
      perfringens type D enterotoxemia are described. Of 16 animals inoculated
      intraduodenally with a whole culture of this microorganism and a starch solution
      in the abomasum, 12 developed clinical signs including increased respiratory
      efforts, recumbency, paddling, bleating, convulsions, blindness, and
      opisthotonus. Diarrhea was not observed in any of the animals. The time lapse
      between the beginning of intraduodenal infusion and onset of clinical signs
      varied between 30 minutes and 26 hours, and the clinical course varied between 1
      and 9 hours. Gross postmortem changes were observed in these 12 animals and
      included pulmonary edema; excess pericardial, peritoneal, or pleural fluid with
      or without strands of fibrin; liquid small intestinal contents; leptomeningeal
      edema; cerebellar coning; and subcapsular petechiae on kidneys. Histological
      changes consisted of severe edema of pleura and interlobular septa and around
      blood vessels and airways and acidophilic, homogeneous, proteinaceous
      perivascular edema in the brain. Five of 12 animals (42%) with clinical signs
      consistent with enterotoxemia lacked specific histological lesions in the brain.
      None of the intoxicated or control animals developed nephrosis. Glucose was
      detected in the urine of 3 of 6 animals that were tested for this analyte. These
      results stress the importance of the use of histological examination of the
      brain, coupled with epsilon toxin detection, for a definitive diagnosis of C.
      perfringens type D enterotoxemia in sheep.

PMID- 15460323
TI  - Efficacy of immunologic assays for the detection of Johne's disease in dairy cows
      fed additional energy during the periparturient period.
AB  - This study was designed to evaluate if the immunosuppression typically observed
      during the immediate periparturient period (3 weeks before and after calving) in
      dairy cows influences the effectiveness of diagnostic tests for the detection of
      Johne's disease; and, if providing additional energy to the cows during this
      period would minimize any immunosuppressive effects. Twelve dairy cows naturally
      infected with Mycobacterium paratuberculosis were fitted with rumen cannulas in
      late gestation and assigned to treatment groups: control, n = 6; or stuffed, n =
      6. Cows in the control group were allowed to consume feed ad libitum. Cows
      assigned to the stuffed treatment group were also fed ad libitum but received
      additional total mixed ration by manually stuffing their rumens with refused feed
      to maintain a dry matter intake of 2% body weight/day before calving and 2.5%
      body weight/day after calving. Parturition had a significant impact on immune
      function with significant reductions in M. paratuberculosis-specific antibodies
      detected in the serum and milk regardless of treatment group. Similarly, in vitro
      immunoglobulin production was decreased at calving for both treatment groups. In
      addition, stuffing cows modulated cell-mediated immune function by reducing
      antigen-specific lymphocyte proliferation and interferon-gamma production after
      calving. Shedding of M. paratuberculosis in the milk was apparent in 58% (7/12)
      of cows after parturition with no difference noted between control and stuffed
      animals. Parturition had no major effect on fecal shedding of cows regardless of
      treatment. These data suggest that parturition had a significant effect on immune
      function parameters including diagnostic tests for paratuberculosis. Furthermore,
      providing additional energy to cows with Johne's disease did not preclude
      immunosuppressive effects during the periparturient period.

PMID- 15460324
TI  - Fibrosarcoma with lung and lymph node metastases in an Asian elephant (Elephas
      maximus).
AB  - A case of fibrosarcoma with lung and lymph node metastases in a 54-year-old
      female Asian elephant (Elephas maximus) is described. After pododermatitis of 2
      years duration in the right forefoot, a mass developed in the lateral toenail. At
      postmortem, metastasis to the right axillary lymph node and both lungs was noted.
      Microscopic examination of primary and metastatic sites revealed infiltrating
      bundles of spindle cells, with fairly distinct cell borders, variable amounts of
      eosinophilic cytoplasm, and elongate or oval nuclei. Tumor cells were often
      arranged in interwoven bundles and herringbone patterns. Mitotic figures were
      numerous and frequently bizarre. The diagnosis of fibrosarcoma with lung and
      lymph node metastases was made on the basis of histologic features and positive
      immunohistochemical staining for vimentin.

PMID- 15460325
TI  - Atypical hypoplastic left ventricular syndrome in a calf.
AB  - An 8-day-old male Angus calf was presented to the University of Illinois,
      Veterinary Teaching Hospital, Urbana, IL, for lethargy, weakness, and poor suckle
      reflex. Clinical evaluation revealed a strong left-sided heart murmur and a split
      S2 sound. The calf died within 48 hours. Necropsy revealed a combination of the
      following cardiac defects: left ventricular hypoplasia, high ventricular septal
      defect, left auricular atresia with mitral valve aplasia, patent foramen ovale,
      patent ductus arteriosus, and pulmonary trunk atresia. Mild suppurative pneumonia
      with pulmonary edema and congestion were also present. This combination of
      defects appears to be similar to the hypoplastic left heart syndrome in humans
      and is reported here for the first time in cattle.

PMID- 15460326
TI  - Isolation and antimicrobial susceptibilities of bacterial pathogens from bovine
      pneumonia: 1994--2002.
AB  - Between 1994 and 2002, a total of 390 (46.3%) Mannheimia haemolytica, 292 (34.7%)
      Pasteurella multocida, and 160 (19.0%) Histophilus somni were isolated at the
      Oklahoma Animal Disease Diagnostic Laboratory from lungs from 6-18-month-old beef
      cattle with pneumonia. The ratio of M. haemolytica isolations to P. multocida
      isolations decreased from 3.1 in 1994 to 0.8 in 2000 while increasing to 1.5 in
      2002. Mannheimia haemolytica isolations significantly (P < 0.05) decreased from
      62.5% in 1994 to between 30.6% and 50.4% in 1998--2002. Pasteurella multocida
      isolations significantly (P < 0.05) increased from 20.0% in 1994 to between 28.6%
      and 47.4% in 1998--2002. Histophilus somni isolations were <19% except in 1998
      (40.8%) and 1999 (23%). Antimicrobial susceptibilities for M. haemolytica
      significantly declined for erythromycin (P = 0.0001), florfenicol (P = 0.0004),
      spectinomycin (P = 0.0001), and tilmicosin (P = 0.03). For P. multocida,
      antimicrobial susceptibilities significantly declined for erythromycin (P =
      0.0001), florfenicol (P = 0.004), spectinomycin (P = 0.03), sulfachloropyridizine
      (P = 0.028), tetracycline (P = 0.017), tilmicosin (P = 0.0001), and
      trimethoprim/sulfamethoxazole (P = 0.0003). Antimicrobial susceptibilities for H.
      somni were variable for spectinomycin and sulfachloropyridizine, whereas
      susceptibilities to other antibiotics remained consistently high.

PMID- 15460327
TI  - Immunoglobulin G2 deficiency with transient hypogammaglobulinemia and chronic
      respiratory disease in a 6-month-old Holstein heifer.
AB  - A 6-month-old Holstein heifer that was nonresponsive to medical treatment was
      evaluated for chronic respiratory disease. Complete blood count and serum
      chemistry revealed neutrophilic leukocytosis and low globulin levels. Assays for
      bovine leukemia virus, bovine virus diarrhea, and bovine leukocyte adhesion
      deficiency were negative. Serum globulin subclass assays revealed transient low
      concentrations of immunoglobulin (Ig) G1 and IgA, persistent low IgG2, and
      subnormal IgM. Vaccination with 2 doses of multiple, inactived viruses induced
      seroconversion for most viruses. Flow cytometric analysis of blood lymphocyte
      subpopulation demonstrated an increase in CD5+ B-cells. Blood lymphocyte
      proliferation and neutrophil function tests were normal. Results of immunologic
      assays indicated IgG2 deficiency with transient hypogammaglobulinemia.

PMID- 15460328
TI  - Bovine arsenic toxicosis.
AB  - A ranch in central South Dakota had a number of dead calves because of arsenic
      poisoning. The clinical picture included diarrhea, central nervous system signs,
      and death. Gross necropsy findings included adequate body fat, stomachs full of
      normal-appearing ingesta, and large amounts of greenish brown watery fluid in the
      intestine and colon. Microscopically there was severe lymphoid tissue necrosis in
      the mesenteric lymph nodes and gut-associated lymphoid tissue. Chemical analysis
      of kidneys showed no significant amounts of lead; however, kidney arsenic
      concentrations were 25 to 44 ppm. The source was a small pile of Paris Green
      (common name for cupric acetoarsenite) found in an old dump site in the pasture.

PMID- 15460329
TI  - Diagnosis of taenia saginata cysticercosis by immunohistochemical test on
      formalin-fixed and paraffin-embedded bovine lesions.
AB  - A new method of diagnosing cysticercus or larval stage of the human tapeworm,
      Taenia saginata, also known as Cysticercus bovis, in formalin-fixed bovine tissue
      was developed using a monoclonal antibody to T. saginata and avidin-biotin
      complex immunohistochemistry. Grossly recognizable viable and degenerate cysts
      were identifiable after immunohistochemical staining and could be differentiated
      from Sarcocystis, Actinobacillus, or non-cyst, normal bovine structures. Thenew
      test should permit laboratory confirmation of suspected T. saginata cysticercus
      lesions.

PMID- 15460330
TI  - Molecular diagnosis of paramyxovirus infection in snakes using reverse
      transcriptase-polymerase chain reaction and complementary deoxyribonucleic
      acid:ribonucleic acid in situ hybridization.
AB  - Identification of ophidian paramyxovirus (OPMV) nucleic acid was accomplished in
      11 of 14 snakes by a reverse transcriptase-polymerase chain reaction (RT-PCR)
      assay that detected a 153-bp region of the OPMV genome in total RNA extracted
      from paraffin-embedded tissues and cell culture. The RT-PCR protocol amplified a
      portion of the OPMV RNA genome, producing a 153-bp complementary DNA (cDNA)
      product from both fresh and paraffin-embedded tissue samples. In addition,
      cDNA:RNA in situ hybridization localized OPMV in formalin-fixed, paraffin
      embedded tissue specimens to specific tissues and cells. This latter technique
      increased the degree of specificity with which a diagnosis of OPMV could be made.

PMID- 15460331
TI  - Use of conventional and real-time polymerase chain reaction for confirmation of
      Mycobacterium avium subsp. paratuberculosis in a broth-based culture system ESP
      II.
AB  - The ESP II Culture System (ESP II), a broth-based culture system, has been
      modified and optimized for culturing Mycobacterium avium subsp. paratuberculosis
      (M. paratuberculosis) in animal feces since 2000. Conventional and real-time
      polymerase chain reaction (PCR) assays based on the IS900 sequence were performed
      as confirmatory tests for M. paratuberculosis in ESP II liquid culture medium.
      There were no differences between test results of conventional and real-time PCR
      assays. During the 5-week incubation period, if acid-fast bacilli (AFB) were
      detected in ESP culture-positive samples, IS900 PCR assays were performed to
      confirm whether those AFB were M. paratuberculosis. At the end of the 5-week
      incubation, AF staining was performed on all ESP II-negative cultures to screen
      any false-negative cultures; IS900 PCR assays were performed on AFB-positive
      cultures. During a period of 1 year, of a total of 18,499 ESP II cultures, 2,814
      (15.2%) PCR confirmation assays were performed. Of those, 2,259 (80%) were both
      ESP and PCR positive; 104 (4%) were ESP positive and PCR negative; 423 (15%) were
      ESP negative and PCR positive; 28 (1%) were both ESP and PCR negative. The AF
      staining step after the 5-week incubation produced 423 (15%) more PCR-positive
      cultures. Of a total of 2,814 AFB-positive cultures, 132 (5%) were not confirmed
      as M. paratuberculosis. Further studies are needed for speciation of non-M.
      paratuberculosis isolates.

PMID- 15460332
TI  - Suspected metastatic coccygeal chordoma in a ferret (Mustela putorius furo).
AB  - A chordoma was removed from the tail base of a 6.5-year-old ferret (Mustela
      putorius furo). A nodule was observed in the area of tumor development when the
      ferret was purchased at 3 months of age. Although the nodule did not enlarge for
      2 years, slow, steady growth of the tumor was observed for 4 years before
      surgical removal. Eight months after removal of the chordoma, the ferret
      developed 2 cutaneous masses. One was adjacent to the vulva, close to where the
      chordoma had been removed from, whereas the other was in the nasofacial region.
      After 4 months of slow growth, both masses were removed and both were
      histologically and immunohistochemically consistent with chordoma. Over the next
      8 weeks, additional masses developed in the facial, maxillary gingival, and
      scapular regions. Enlargement of the gingival mass caused dysphagia, and the
      ferret was euthanized. Although a necropsy was not performed, these additional
      masses had a clinical appearance and texture that was similar to the 2 previously
      removed cutaneous chordomas. To the authors' knowledge, this is the first report
      of a ferret coccygeal chordoma that developed close to the base of the tail.
      Ferret chordomas have been reported previously to metastasize to the subcutis
      overlying the tumor. However, this is the first report of a ferret chordoma that
      metastasized to a location distant to the primary site of neoplasm development.
      Cell proliferation indices did not predict this metastatic behavior. It is
      hypothesized that the long clinical period before removal may have predisposed
      this neoplasm to metastasis. Observations from this case suggest that chordomas
      in ferrets may have metastatic potential and so should be removed promptly.

PMID- 15460333
TI  - Molecular epidemiology of two fowl cholera outbreaks on a free-range chicken
      layer farm.
AB  - Two outbreaks of fowl cholera on a multiage free-range egg farm were
      investigated. The outbreaks occurred in 1994 and 2002. A total of 22 strains of
      Pasteurella multocida were available for study, 11 from the 1994 outbreak and 11
      from the 2002 outbreak. Lesions typical of acute fowl cholera were seen in the
      1994 outbreak, whereas both acute and chronic fowl cholera occurred in the 2002
      outbreak. The isolates were examined in an extended phenotypic typing
      methodology, by a P. multocida-specific polymerase chain reaction (PCR), by the
      Heddleston somatic serotyping scheme, and by restriction endonuclease analysis
      (REA) typing using the enzyme HpaII. All 22 strains had the same phenotypic
      properties, all were confirmed as P. multocida by PCR, all were Heddleston
      serovar 4, and all had the same REA pattern. The results indicate that these 2
      outbreaks were caused by the same clone of P. multocida--despite the 8-year time
      period between the outbreaks.

PMID- 15460334
TI  - Isolation of an adenovirus and an adeno-associated virus from goat kids with
      enteritis.
AB  - A dairy goat operation in Minnesota experienced a sudden, markedly increased
      mortality among its neonatal goats. Approximately 60 of 130 kids (46%) died. The
      animals had diarrhea and dyspnea of 1-2 days duration before death. Necropsy of 4
      goat kids revealed marked, acute, catarrhal enteritis and fibrinous
      pleuropneumonia. Mannheimia haemolytica was isolated from the lungs. Basophilic
      inclusion bodies filling the entire nucleus were present in enterocytes of the
      ileum of 3 goats. Adenoviral particles were detected in the feces by electron
      microscopy and adenovirus was subsequently isolated from the intestinal content
      together with a parvo-like virus (dependovirus). Morphology, physicochemical
      characteristics, and neutralization tests indicated that the adenovirus resembled
      ovine adenovirus-2 (OAdV-2). However, the PstI restriction endonuclease pattern
      produced by the goat adenovirus was distinct from that of OAdV-2. This is the
      first report of enteritis in goats with an adenovirus antigenically related to
      OAdV-2 and with a parvo-like dependovirus.

PMID- 15460335
TI  - Eye infections due to Listeria monocytogenes in three cows and one horse.
AB  - A retrospective study was conducted to determine case histories, microbiological
      characteristics, and molecular subtypes associated with Listeria monocytogenes
      infections of the eye in large animals. For selected cases, environmental L.
      monocytogenes contamination patterns on case farms were also evaluated to probe
      for potential sources and spread of listerial eye infections. Records of 170 L.
      monocytogenes isolates from animal infections were reviewed to determine the
      fraction of isolates associated with eye infections (conjunctivitis, keratitis,
      and uveitis) of animals and to gather information on the clinical history of
      these cases. Overall, 4 of 170 Listeria monocytogenes isolates were associated
      with eye infections; 3 of these had occurred in cows and 1 in a horse. Molecular
      subtyping (by EcoRI ribotying) showed that 4 different L. monocytogenes subtypes
      were isolated from these 4 cases; the same ribotypes had previously been found
      among invasive animal listeriosis infections. Although a variety of L.
      monocytogenes subtypes were isolated from environmental sources, on 1 farm, the
      same ribotype associated with the eye infection was also isolated from a fecal
      sample of a healthy animal and from a soil sample. The data reported in this
      study further suggest that L. monocytogenes can be a cause of eye infections in
      several animal species. Listerial eye infections do not seem to require specific
      pathogen-related virulence characteristics but rather seem to be a function of
      environmental or host factors, such as direct exposure of the eyes of susceptible
      animals to high numbers of the pathogen. Although listerial eye infections are
      rarely diagnosed because of its ubiquitous nature, L. monocytogenes may have to
      be considered more commonly as a causative agent of eye infections in ruminants
      and horses.

PMID- 15460336
TI  - Rapid and simple mutation screening of G(M1) gangliosidosis in Shiba dogs by
      direct amplification of deoxyribonucleic acid from various forms of canine whole
      blood specimens.
AB  - This report describes a rapid and simple method for mutation screening of G(M1)
      gangliosidosis in Shiba dogs by direct amplification of DNA from canine whole
      blood specimens using a novel polymerase chain reaction (PCR) reagent cocktail,
      which can eliminate the DNA extraction process and amplify the genomic DNA
      directly from human or murine whole blood. The strategy of this mutation
      screening is based on the identification of a nucleotide deletion by restriction
      enzyme analysis, coupled with the direct PCR amplification. The target sequence
      of the canine beta-galactosidase gene could be amplified directly from various
      forms of canine whole-blood specimens, including anticoagulated blood, blood
      stored frozen for 1 year, dried blood held in filter paper for 1 year at room
      temperature, and dry powder of blood stripped from Giemsa-stained blood films,
      which had been prepared 10 years earlier, resulting in the determination of
      genotypes in all the specimens. This method simplified the molecular diagnosis
      and carrier screening of G(M1) gangliosidosis in Shiba dogs, making it simple to
      examine specimens from the large, widely distributed population of these dogs.

PMID- 15460337
TI  - Utility of high-performance liquid chromatography in the characterization of
      iatrogenic sodium diatrizoate-induced seizures in a horse.
AB  - Diagnostic evaluation of a mildly ataxic young gelding Quarterhorse included a
      contrast myelogram. Unfortunately, sodium diatrizoate was inappropriately
      administered by intrathecal injection resulting in severe unrelenting seizure
      activity and necessitated the destruction of the animal. The contrast agent was
      identified by analyzing cerebrospinal fluid by high-performance liquid
      chromatography and confirmed with probe mass spectrometric analysis. This
      contrast agent is highly ionic, has high osmolarity, and also blocks
      neurotransmission at specific receptors; for these reasons it is contraindicated
      for use in myelography. This is the first report of intrathecal administration of
      this agent in a horse, although there has been a previous report of similar
      untoward reactions in a dog, and numerous cases have been reported in humans.

PMID- 15460338
TI  - Congenital polycystic kidney in a white-tailed deer (Odocoileus virginianus).
AB  - Polycystic kidney and liver disease was seen in a stillborn white-tailed deer
      (Odocoileus virginianus) fawn. Bilaterally enlarged kidneys were characterized by
      severe dilatation of all renal tubules. Glomeruli were sparse, small, and located
      within a dilated Bowman's capsule. The liver was characterized by marked
      periportal fibrosis, biliary hyperplasia, and bile duct ectasia with dilated
      ducts containing inspissated bile. The presentation and morphology of this case
      are most similar to autosomal recessive polycystic disease in humans.

PMID- 15460339
TI  - Abortion and ulcerative posthitis associated with caprine herpesvirus-1 infection
      in goats in California.
AB  - Three outbreaks of late-gestation abortions in does and ulcerative posthitis in
      bucks, associated with caprine herpes virus-1 (CHV-1), in California are
      described. In herd A, 10 of 17 does aborted in a 7-day period, whereas in herd B,
      4 of 130 does aborted in a 45-day period and in herd C, 100 of 300 does aborted
      in a 3-week period. Most fetuses had multifocal pinpoint depressed foci with a
      zone of hyperemia on external and cut surfaces of the kidneys, liver, lungs, and
      adrenal glands. Histologically, scattered multifocal areas of necrosis with mild
      neutrophilic infiltrate were observed in kidneys, brain, liver, adrenal glands,
      and lungs of most fetuses of the 3 herds. Large amphophilic intranuclear
      inclusion bodies, which displaced the chromatin, were observed in cells within
      and around the necrotic foci in kidneys and adrenal glands. Particles 85-113 nm
      in size with morphology compatible with herpes virus were observed in the nuclei
      of these cells when examined by electron microscopy. Irregular, shallow, red
      ulcers were observed in the prepuce of 1 buck from herd C. Prepuce biopsies from
      this animal had necrosis of the superficial mucosal epithelium and severe
      submucosal lymphoplasmocytic infiltrates. Large intranuclear amphophilic
      inclusion bodies were observed in most cells of the stratum spinosum of the
      preputial epithelium, but no viral particles were observed in these cells.
      Caprine herpes virus-1 was isolated from tissue pools of fetuses from the 3 herds
      but not from prepuce biopsies. Positive results were obtained when tissues of a
      fetus from herd C were processed by a polymerase chain reaction technique to
      amplify the amino terminus of the glycoprotein C gene of CHV-1. Sera from aborted
      does from herds B and C and from the 3 bucks from herd C had high antibody titers
      to CHV-1. The results presented here support the hypothesis that the male goat is
      involved in the transmission of CHV-1. However, other forms of transmission
      cannot be ruled out.

PMID- 15460340
TI  - NAPNES board of directors position paper regarding supply, demand, and use of
      licensed practical nurses.

PMID- 15460341
TI  - I am just an LPN.

PMID- 15460342
TI  - Medication use in the elderly. Part I: psychotropic drugs.

PMID- 15460343
TI  - Listening--a nursing strategy to transcend culture.
AB  - When nurses relate to patients from diverse cultures many times fears and
      anxieties of the patient and family, differences in communication style,
      differences in values, and insecurities interfere with the therapeutic nurse
      patient relationship. Active listening is an intentional strategy that can
      provide a bridge across cultural barriers, allow cultural bias to be dealt with
      constructively, and can assist the nurse and patient in ensuring that patient
      needs are met. Active listening benefits not only the patient but the nurse and
      can result in the delivery of culturally competent care to the diverse patient.

PMID- 15460344
TI  - The nurse-physician relationship: is collaboration the answer?

PMID- 15460345
TI  - Promoting teacher quality and retention in special education.
AB  - Qualified special educators are needed to carry out research-based practices in
      schools. The shortage of special educators, the high numbers of uncertified
      teachers, and high attrition rates threaten the practice of science in the
      schoolhouse and, consequently, the education that students with disabilities
      receive. If teachers are to use research-based practices to benefit students with
      disabilities, care must be directed toward teachers, what they do, and the
      complex conditions in which their practice occurs. In this discussion, I focus on
      four factors that are important to special education teacher retention-
      responsive induction programs, deliberate role design, positive work conditions
      and supports, and professional development. These retention-enhancing factors
      also serve to cultivate qualified special educators by providing the conditions
      in which they can thrive and grow professionally.

PMID- 15460346
TI  - An epidemiological study of number processing and mental calculation in Greek
      schoolchildren.
AB  - The aim of this study was to validate and standardize an instrument for the
      diagnosis of developmental dyscalculia (mathematics disorder) in a Greek
      population and to obtain relevant epidemiological data. We used the
      Neuropsychological Test Battery for Number Processing and Calculation in Children
      (NUCALC) in a community sample of 240 students ages 7 to 11 years from urban and
      rural schools. There were no differences between genders in arithmetical
      performance; however, the effects of grade and socioeconomic level were
      significant. Prevalence was higher in the rural than in the urban area. A cross
      cultural comparison of the Greek data with those obtained with the same
      instrument in other countries in schoolchildren of the same age was performed.

PMID- 15460347
TI  - Visual and language processing deficits in compensated and uncompensated college
      students with dyslexia.
AB  - In seven experiments, we investigated whether compensated and uncompensated
      adults with dyslexia show different patterns of deficits in magnocellular visual
      processing and in language processing tasks. In four visual tasks, we failed to
      find evidence of magnocellular deficits in either group. However, both groups of
      adults with dyslexia showed deficits in component language skills, and the degree
      of reading impairment predicted the nature and extent of these deficits.
      Uncompensated readers showed deficits in orthographic and especially phonological
      coding and awareness and were slower on rapid naming. Compensated readers showed
      word and nonword performance below controls but better than the uncompensated
      readers. The compensated group was not significantly less accurate than controls
      on phonological awareness, nor significantly worse overall on rapid naming.

PMID- 15460348
TI  - Emotional adjustment and school functioning of young adolescents with multiple
      versus single learning disabilities.
AB  - Early adolescents (Grades 6-8) with multiple learning disabilities (LD; reading
      and math) in inclusive settings were compared to adolescents with single LD
      (reading or math) and typically achieving (TA) peers regarding their psychosocial
      functioning in two areas of adolescent well-being: emotional adjustment and
      school functioning. The Behavior Assessment System for Children (Reynolds &
      Kamphaus, 1998) Self-Report of Personality for adolescents was used to determine
      well-being. One hundred twenty middle school students-15 boys and 15 girls in
      each group-were included in the current study. The results confirmed that
      adolescents with multiple LD (reading and math) reported poorer functioning
      (i.e., higher T scores) on school maladjustment, clinical maladjustment,
      emotional symptoms index, attitude to school, atypicality, and depression when
      compared to TA peers but not when compared to peers with a single LD (reading or
      math). All three groups differed from the TA group (but not from each other) on
      sense of inadequacy, with the multiple LD group reporting the highest T scores.
      Additional analyses indicated significant differences between girls and boys,
      regardless of disability status. Girls reported higher T scores on the emotional
      symptoms index, social stress, and depression, but boys reported greater school
      maladjustment and sensation seeking. Implications for practice and
      recommendations for future research are discussed.

PMID- 15460349
TI  - Early reading instruction for children with reading difficulties: meeting the
      needs of diverse learners.
AB  - Several multiple-probe-across-participants design studies were employed to
      evaluate the effectiveness of a supplemental tutoring intervention using Read
      Well (Sprick, Howard, & Fidanque, 1998-2000). In Year 1, we conducted two studies
      with 7 first-, second-, and third-grade children (1 girl and 6 boys), who were
      classified as having learning disabilities, having attention-deficit disorder, or
      being English language learners and were identified by their teachers as poor
      readers. The results of the two studies indicated that 3 of the 5 children who
      received Read Well instruction showed improvement in passage fluency. Student
      performance on other measures of reading and comprehension was varied.
      Differences in student characteristics and in the amount of Read Well instruction
      received (2 to 7 weeks) seemed to account for the differences in performance. In
      Year 2, we implemented the same tutoring intervention for a longer duration (up
      to 16 weeks) and included 5 children in second and third grades (2 girls and 3
      boys) with reading difficulties. Two of these children had previously
      participated in the Year 1 studies. The results indicated growth in reading,
      spelling, and comprehension for most children. Overall, the findings from Year 1
      and 2 studies indicate the benefits of increased instructional intensity and
      duration for children who struggle with emerging reading skills.

PMID- 15460350
TI  - Naming speed deficits in adults with reading disabilities: a test of the double
      deficit hypothesis.
AB  - The present study investigated the persistent nature of naming speed deficits
      within the context of the double-deficit hypothesis in a university sample of
      adults with reading disabilities (RD). Twenty-five university students with RD
      were compared to 28 typically achieving readers on measures of reading skill,
      phonological processing, and naming speed. The results indicated that both naming
      speed and phonological processing deficits characterized the RD group. In a
      regression analysis, neither naming speed nor phonological processing were
      important variables in explaining comprehension when reading rate was in the
      model. The results of the present study are mixed at best and are consistent with
      earlier conclusions that support for the double-deficit hypothesis of dyslexia
      remains limited.

PMID- 15460351
TI  - Neurodevelopmental characteristics of children with learning impairments
      classified according to the double-deficit hypothesis.
AB  - The double-deficit model has been examined primarily in relation to reading. We
      investigated whether children classified according to the double-deficit model
      would exhibit differences in other neuropsychological domains. Children referred
      for learning problems (N = 188), ages 7 to 11, were classified by double-deficit
      subtype. Only three of the four groups predicted by the model could be
      identified. There were no group differences in IQ or attention problems. The
      three groups showed different neuropsychological profiles, involving functional
      domains other than reading and language. Differences also emerged in nonverbal
      low-level information processing. The double-deficit group was generally most
      severely affected. The double-deficit groupings identify children with different
      neuropsychological profiles and variation in the efficiency of basic online
      information processing, extending beyond the oral and written language domain.

PMID- 15460352
TI  - Psychometric analysis of the Minnesota Test of Critical Thinking.
AB  - With the increase over the past two decades in interest in critical thinking
      instruction, reliable and valid means for measuring critical thinking are
      necessary. The Minnesota Test of Critical Thinking was developed to measure
      critical thinking as defined by the American Philosophical Association in 1990.
      The present purpose was to explore the structure and reliability of the
      intervention and its instantiation of the critical thinking framework. Analyses
      of responses from 151 adult participants gave estimates of reliability varying
      from .29 to .78. A factor analysis of the test scores supported critical thinking
      conceptualized as a single, latent trait. With further refinement, the invention
      should become a valuable measure of general critical thinking skills of upper
      division secondary and postsecondary students.

PMID- 15460353
TI  - Family and ability correlates of academic grades: social status group
      differences.
AB  - In a continuation of work by Marjoribanks (2003), using a sample of 150 seventh
      grade students, relationships among Parent Involvement as defined by factor
      scores of four measures of parents' involvement completed by teachers: teacher
      parent contacts, teacher-parent communication, parents' involvement at home, and
      parents' participation in school, Intellectual Ability as defined by Verbal
      Intelligence using the Yuste's Differential and General Aptitudes Battery-M, and
      Academic Grades as defined by the average grade for all subject matter were
      examined. Analysis showed different predictive models for children's academic
      achievement as a function of social status. For children of low and middle social
      status, Intellectual Ability was the single predictor. For children of high
      social status the predictors were Parents' Involvement and the interaction of
      Parents' Involvement and Intellectual Ability.

PMID- 15460354
TI  - Relationship of sports experience and ego development of adolescent Japanese
      athletes.
AB  - This study examined the relationship of sports experience with ego development. A
      questionnaire was used to assess experience of Crisis, Exploration, and
      Commitment in the issues of Athletic Performance and of Being a Teammate in 782
      adolescent Japanese athletes (423 boys, M age = 15.2 yr.; 359 girls, M age = 15.0
      yr.). Their Ego Levels were assessed using the Washington University Sentence
      Completion Test. Correlations indicated that scores on Crisis, Exploration, and
      Commitment in the issues of Athletic Performance and Being a Teammate were
      generally associated with Ego Development. Multiple regression analyses indicated
      that, for boys, the issue of Athletic Performance was closely associated with Ego
      Development, while for girls, the issue of Being a Teammate was closely
      associated with Ego Development. Sports experience with crisis, exploration, and
      commitment may be related to accommodation, which is, in turn, related to ego
      development. The sex differences on issues related to ego development may be
      associated with differences in sex-role development for boys and girls.

PMID- 15460355
TI  - Integrity, conscientiousness, and honesty.
AB  - Undergraduate volunteers from the Psychology participant pool (N=86, age M=22.7,
      SD=4.8 yr.; 72 of 86 were female) took two tests, a commercially available
      integrity test (the Personnel Selection Inventory) and the NEO-Five Factor
      Inventory. Later in the study, each participant was given an opportunity to
      report dishonestly the amount of time spent in the laboratory and thus to receive
      more extra-credit points than earned. An observer recorded participants' actual
      times in the laboratory to provide an accurate assessment of participants'
      honesty. Analysis indicated that the Personnel Selection Inventory did not
      predict whether the participant was honest or dishonest in reporting time spent.
      Conscientiousness as measured by the NEO-Five Factor Inventory, however, not only
      predicted behavior, but did so significantly better than did the Personnel
      Selection Inventory. The study provides new information about the value of
      integrity tests by comparing integrity and personality tests in the simultaneous
      prediction of a specific criterion.

PMID- 15460356
TI  - Sustained attention and visual processing speed in children and adolescents with
      bipolar disorder and other psychiatric disorders.
AB  - To investigate the cognitive functioning of children and adolescents with bipolar
      illness, 112 child and adolescent psychiatric inpatients and day-hospital
      patients at a state psychiatric hospital were administered the Wechsler
      Intelligence Scale for Children-III (WISC-III) as part of an admission
      psychological assessment. There were 22 patients with Bipolar Disorder and 90
      with other psychiatric disorders; all were between 8 and 17 years of age. The
      patients with Bipolar Disorder had a mean age of 14 yr., a mean Verbal IQ of 78,
      a mean Performance IQ of 76, and a mean Full Scale IQ of 75. When their WISC-III
      scores were compared with those who had Schizophrenia Spectrum disorders
      (Schizophrenia and Schizoaffective Disorder), Psychosis Not Otherwise Specified,
      Attention Deficit Hyperactivity Disorder, and Conduct Disorder and Oppositional
      Defiant Disorder, there were no significant between-group mean differences for
      Verbal IQ, but patients with Bipolar Disorder had a significantly lower mean
      Performance IQ than those with ADHD and those with Conduct Disorder and
      Oppositional Defiant Disorder. Contrary to the expectation that the patients with
      Bipolar Disorder might have better sustained attention (higher Digit Span scores)
      than those with Schizophrenia Spectrum disorders and worse visual processing
      speed (lower Coding scores) than the other diagnostic groups, the bipolar
      patients' Digit Span and Coding scores did not differ significantly from those of
      the other groups. The patients with Psychosis, Not Otherwise Specified had
      significantly lower mean Performance IQ, Full Scale IQ, and Coding than the ADHD
      and the Conduct Disorder and Oppositional Disorder groups.

PMID- 15460357
TI  - Relationship of subjective chronic fatigue to academic performance.
AB  - Psychophysiological variables which affect the activity of schoolchildren with
      subjective chronic fatigue were studied. For 32 Japanese elementary school
      children, 15 boys and 17 girls in Grade 4, the major finding was that the
      majority of children with subjective chronic fatigue were less active in school.
      The motor and academic performance of children with greater subjective chronic
      fatigue were significantly inferior to those of normal children. Good learning
      was associated with less drowsiness. These findings suggest that subjective
      chronic fatigue is closely related to daily activities, especially adjustment to
      school.

PMID- 15460358
TI  - Effect of relaxation on working memory and the Bispectral Index of the EEG.
AB  - Beneficial effects of relaxation on cardiovascular and immune functions and on
      memory has been implied but an empirical relationship between task performance
      and anxiety reduction has not been reported. In this study, we investigated
      whether guided imagery of relatively short duration would decrease S-Anxiety and
      electroencephalogram Bispectral Index and improve working memory. 42 participants
      (age: M=39, SD=11, 14 men, 28 women, university students and VA Medical Center
      employees, recruited by their professor or by fellow employees) underwent
      relaxation by 16-min. guided imagery or no treatment (control). Spielberger's
      State-Trait Anxiety Inventory and the WAIS-III Letter-Number Sequencing Test were
      administered before and after relaxation. S-Anxiety and BIS Index decreased and
      the Letter-Number test score increased by 30% after relaxation but not in the
      control group. This score was higher for participants with low anxiety and BIS
      Index. There was no significant difference between the groups before treatment.
      The results suggest that guided imagery of short duration produces relaxation as
      measured by psychological and neurophysiological indices and improves working
      memory performance.

PMID- 15460359
TI  - Reports of attempted suicide among Brazilian addicts.
AB  - Both substance dependence and depressive mood seem to be associated with
      increased suicide risk. Clinical information on suicide attempts and depressive
      symptoms were obtained from a sample of 211 psychoactive substance dependents
      attending a university clinic program for addicts in Brazil. 49 subjects (23.4%)
      had attempted suicide at least once, and the frequency of reporting attempts was
      4.32 times greater among women than among men. Male addicts also tended to engage
      in potentially more dangerous attempt methods than women. Depressive male addicts
      were 2.17 times more likely to have attempted suicide than nondepressive addicted
      men. Among women, no association could be established between having attempted
      suicide and the presence of depression. Substance addicts have a relatively high
      risk of attempting suicide and the co-occurrence of depression seems to increase
      prevalence of suicidal behavior among men.

PMID- 15460360
TI  - Performance of chronotypes on memory tests during the morning and the evening
      shifts.
AB  - Memory consists of several phases or processes that can be influenced by many
      factors, including the individual's circadian rhythm and the time of day at which
      tests are performed. The present objective was to evaluate the performance on
      memory tests of different chronotypes during the morning and the evening shifts.
      Subjects (21 men and 26 women, between the ages of 20 and 35 yr.) were evaluated
      for memory and metamemory differences in the morning and in the afternoon, using
      a battery of neuropsychological tests composed of the Word List with Emotional
      Content, Visual Memory, Scale-Semantic Memory, Digit Span, Word-Pairs Associated,
      Verbal Fluency Test, and Metamemory questionnaire. In the evening shift, there
      was a statistical difference among chronotypes on the Word List with Neutral
      Content and on the Verbal Fluency Test. In the morning, there were no
      statistically significant differences; however, the morning-type subjects had
      higher scores on the metamemory tests (p<.01), while the evening-type subjects
      had higher scores in the afternoon (p<.01). In spite of their perception, on Word
      Pairs Associated and Word List with Emotional Content, the subjects,
      independently of their chronotype, showed better performance by the evening than
      by the morning shift. These results highlight the importance of controlling the
      shift of day and chronotype in studies with the objective of exploration of human
      performance.

PMID- 15460361
TI  - The Japanese version of the revised Life Orientation Test: reliability and
      construct validity.
AB  - The Japanese translation of the revised Life Orientation Test was completed by
      223 Japanese college students. Factor analysis yielded two factors, namely,
      Optimism and Pessimism. These factor scales showed adequate reliability and
      construct validity.

PMID- 15460362
TI  - Career self-efficacy, career outcome expectations and vocational interests among
      Japanese university students.
AB  - The Social Cognitive Career Model proposes that career interests arise from
      beliefs about capability to execute a course of activity (self-efficacy), and
      beliefs about the consequences of performing particular activities (outcome
      expectations). In our study, 301 Japanese university students were given
      questionnaires including the Vocational Preference Inventory and scales assessing
      Career Self-efficacy and Career-outcome Expectations. Hierarchical multiple
      regression analyses indicated both self-efficacy and outcome expectations were
      significantly related to vocational interests. Outcome expectations accounted for
      significant incremental variance in explaining interests across six of Holland's
      vocational environments. Implications of social cognitive theory for career
      development and interventions among Japanese university students are discussed.

PMID- 15460363
TI  - Sex differences on the five personality factors in Spanish students.
AB  - This study examined sex differences in the Big Five Personality factors in a
      sample of 255 Spanish university students (196 women and 59 men) whose mean age
      was 21.4 yr. (SD=3.91). They responded to the short Spanish version of the Big
      Five Personality scale. The goals of this study were first, to check the utility
      of this scale to evaluate personality traits in the Spanish university
      population, and, second, to check the sensitivity of this shorter scale in
      evaluating possible differences between sexes on these factors of personality.
      Analysis supported the published factorial structure, and significant differences
      were found between men and women on the factors of Extraversion, Neuroticism, and
      Conscientiousness.

PMID- 15460364
TI  - Disposing of the empty shopping market cart--an informal look.
AB  - An informal enquiry suggested that only about one out of five shoppers, when
      finished using shopping carts, returned them to a designated depository.

PMID- 15460365
TI  - Aggressive behaviour in slot machine gamblers: a preliminary observational study.
AB  - Gambling is acknowledged to have many negative effects on individuals. However,
      from a psychological perspective, aggression as an outcome of gambling has been
      largely overlooked to date. The incidence of aggressive behaviour was monitored
      in 303 slot machine players over four 6-hr. observation periods. Analysis
      identified four types of common aggressive behaviour. These were (1) verbal
      aggression towards the gambling arcade staff, (2) verbal aggression towards the
      slot machines, (3) verbal aggression towards other slot machine players, and (4)
      physical aggression towards the slot machines. The findings add support to the
      increasing number of studies highlighting a possible link between gambling and
      aggression.

PMID- 15460366
TI  - Two measures of affect and emotion in Italian children aged 6 to 11 years.
AB  - The authors investigated the relation between affective and cognitive processes
      in fantasy play and emotional understanding of 50 Italian children (25 boys and
      25 girls) enrolled in regular elementary school in Northern Italy. Children were
      administered a standardized play task, the Affect in Play Scale, and answered
      questions about their understanding of emotions. Consistent, yet modest,
      relationships were found between dimensions of fantasy play and emotional
      understanding.

PMID- 15460367
TI  - Comorbidity of DSM-IV Personality Disorders in unipolar and bipolar affective
      disorders: a comparative study.
AB  - The aim of this study was to compare the prevalence of Personality Disorders
      assessed by Structured Clinical Interview for Axis-II in 155 inpatients diagnosed
      with Unipolar Disorder vs inpatients with Bipolar Disorder (39). The most
      frequent Axis II diagnoses among Unipolar inpatients were Borderline (31.6%),
      Dependent (25.2%), and Obsessive-Compulsive (14.2%) Personality Disorders. Among
      Bipolar inpatients, the most prevalent personality disorders were Borderline
      (41%), Narcissistic (20.5%), Dependent (12.8%), and Histrionic disorders (10.3%).
      Using chi squared analysis, few differences in distribution emerged between the
      two groups: Unipolar patients had more recurrent Obsessive-Compulsive Personality
      Disorder than Bipolar patients (chi(1)2=6.24, p<.005). Comorbid Narcissistic
      Personality Disorder was significantly more frequent in the Bipolar than in the
      Unipolar group (chi(1)2=6.34, P<.01). Considering the three clusters (DSM-IV
      classification), there was a significant difference between the groups, Cluster C
      (fearful, avoidant) diagnoses being more frequent in the Unipolar than in the
      Bipolar group (48.4% vs 20.5%, respectively). Cluster B (dramatic, emotionally
      erratic) diagnoses were found more frequently in patients with Bipolar Disorders
      (71.8% vs 45.2% in Unipolar patients, chi(2)2=10.1, p<.006). The differences in
      the distribution and prevalence of Personality Disorders between the two patient
      groups are discussed.

PMID- 15460368
TI  - An exploration of prevalence of domestic violence in same-sex relationships.
AB  - The prevalence of domestic violence in a sample of 33 men and 33 women currently
      or previously in same-sex relationships was assessed. Data were collected through
      a mail survey in the state of Virginia. Of 1000 surveys sent out 66 usable ones
      were returned (response rate = 6.6%). Analysis indicated that 34 had experienced
      some form of domestic violence, but significant differences between male and
      female respondents were not detected. When data from this same-sex sample were
      compared with those of the heterosexual sample of the National Violence Against
      Women Survey, intimate partner assault may be more prevalent against gay men than
      against heterosexual men, but there was no significant difference between
      lesbians and heterosexual females.

PMID- 15460369
TI  - Multimodal classical conditioning of fear: contributions of direct,
      observational, and verbal experiences to current fears.
AB  - The authors propose that a multimodal classical conditioning model be considered
      when clinicians or clinical researchers study the etiology of fears and anxieties
      learned by human beings. They argue that fears can be built through the combined
      effects of direct, observed, and verbally presented classical conditioning
      trials. Multimodal classical conditioning is offered as an alternative to the
      three pathways to fear argument prominent in the human fear literature. In
      contrast to the three pathways position, the authors present theoretical
      arguments for why "learning by observation" and "learning through the receipt of
      verbal information" should be considered classical conditioning through
      observational and verbal modes. The paper includes a demonstration of how data,
      commonly collected in research on the three pathways to fear, would be studied
      differently using a multimodal classical conditioning perspective. Finally, the
      authors discuss implications for assessment, treatment, and prevention of learned
      fears in humans.

PMID- 15460370
TI  - A sense of presence and self-reported performance in international teams.
AB  - Research over the last two decades has explored the relationship between a
      variety of states of consciousness, performance, and motivation. These have
      included flow and a sense of presence in face-to-face, online, and virtual
      environments. This study examined the relationship between presence and flow
      experienced by 75 male and female participants from several Pacific Rim nations
      on 4 international teams and their self-reported performance, enjoyment, and
      motivation associated with team-related tasks. The results indicate that in these
      task situations, which are relatively novel because of their cultural diversity,
      self-reported performance correlated more highly with presence (r=.34, df=72,
      p<.01) than flow (r=.26, df=71, p<.05). Enjoyment and motivation, however,
      correlated more highly with flow (r =.60, df=71, p<.01 and r=.40, df=71, p<.01,
      respectively) than presence (r=.26, p<.05 and r=.25, p<.05). These findings
      suggest the need to explore further the relationship between activity- or task
      related states of consciousness, the characteristics of the tasks involved,
      particularly in terms of their novelty, and the effect on performance and
      motivation.

PMID- 15460371
TI  - Cigarette smoking and depressive symptoms: a longitudinal study of adolescents
      and young adults.
AB  - Cigarette smoking and depressive symptoms have been shown to be related in
      previous research. This paper examined the relationship between cigarette smoking
      and depressive symptoms in a longitudinal sample of 688 adolescents and young
      adults through surveys conducted over 13 yr. The results indicate that a history
      of earlier cigarette smoking in adolescence predicts later depressive symptoms in
      the late twenties. The study also suggests that depressive symptoms during
      adolescence predict cigarette smoking in the late twenties but not above and
      beyond prior smoking. These results help clarify and expand current knowledge on
      the links between cigarette smoking and depression. The results point to several
      clinical implications for treatment of both cigarette smoking and depressive
      symptoms among both adolescents and young adults.

PMID- 15460372
TI  - Effect of behavioral inhibition on interactions in mixed-sex dyads.
AB  - The present studies assessed the effect of behavioral inhibition on interactions
      of college students in mixed-sex groups. In Study 1, 20 participants were
      arranged into two dyadic groups based on self-rated measures of
      approach/withdrawal behavior. These dyads (inhibited men/uninhibited women;
      inhibited women/uninhibited men) were videotaped during an unstructured 5-min.
      interaction in a laboratory. Time series analysis indicated greater behavioral
      covariation in the inhibited men/uninhibited women dyads and less behavioral
      covariation in the inhibited women/uninhibited men dyads. Additional analyses
      indicated a relationship between inhibition and comfort experienced during the
      interaction. Inhibited participants, particularly women, reported feeling
      uncomfortable while interacting with an uninhibited male partner. A second study
      corroborated the findings reported in Study 1 and also noted elevated heart rate
      in the inhibited women. This increased discomfort in women appeared to be related
      to heightened self-consciousness during the interaction.

PMID- 15460373
TI  - Context and test-retest reliability of Kolb's Learning Style Inventory.
AB  - Two groups of students enrolled in a university physical activity course
      volunteered to complete Kolb's Learning Style Inventory at the beginning of and
      the end of a semester to estimate test-retest reliability. A control group (n =
      129) completed the inventory in its original form while the experimental group (n
      = 124) completed the same test but with modified instructions providing a more
      specific focus. Test-retest reliability, assessed using a Pearson product-moment
      correlation, improved for the group given instructions which specified a
      contextual focus.

PMID- 15460374
TI  - Caffeine consumption among adults on benzodiazepine therapy: United States 1988
      1994.
AB  - The concomitant use of benzodiazepines and caffeine was studied to learn if
      caffeine consumption varied as a function of benzodiazepine use. Caffeine may
      antagonize the effects of benzodiazepine and even relatively small amounts can
      aggravate symptoms associated with anxiety disorders. In addition, caffeine can
      cause or aggravate insomnia, one of the main reasons cited for use by the
      subjects in this analysis. Given this, there would seem to be sufficient reason
      for at least some users of benzodiazepines to consider, with their physicians,
      avoiding or limiting caffeine consumption. Data from the Third National Health
      and Nutrition Examination Survey were analyzed to obtain a nationally
      representative sample of benzodiazepine users. Subjects included 253 individuals
      (64% women) whose median age was 54 yr. Approximately 88% of benzodiazepine users
      reported caffeine consumption in the 24-hr. Dietary Recall. 26% of benzodiazepine
      users and 23% of nonusers reported consuming greater than 250 mg of caffeine
      during the 24-hr. reference period. In regression analyses, no significant
      relationships were found between reported caffeine consumption and benzodiazepine
      use. This study suggests that users and nonusers of benzodiazepines ingest
      similar amounts of caffeine even though some users should probably avoid or limit
      caffeine use.

PMID- 15460375
TI  - Persistent neuropsychological problems after 7 years of abstinence from
      recreational Ecstasy (MDMA): a case study.
AB  - This case study concerns a 26-yr.-old male who had consumed large amounts of
      Ecstasy seven years previously. He stated that his increasingly intensive use of
      ecstasy over a 4-yr. period had led to the emergence of multiple psychiatric and
      psychological problems. Given these problems, he stopped using Ecstasy, but the
      problems had not resolved despite seven years of abstinence. The neurocognitive
      profile was very similar to that shown by current heavy Ecstasy users, with
      deficits in immediate and delayed verbal recall, moderately impaired memory
      function, but normal expressive language ability and perceptual functioning.
      Extremely high pathology was evident, including depression and phobic anxiety.
      Severe problems with sleep and sex were also reported. Further studies involving
      larger groups of abstinent former users are needed; adverse sequelae associated
      with intensive Ecstasy use may sometimes be enduring.

PMID- 15460376
TI  - Quality of life assessment in Turkish patients with schizophrenia and their
      relatives.
AB  - Quality of life of first-degree relatives living in the same household with
      patients having schizophrenia has not been sufficiently explored. 30 patients
      with schizophrenia (16 women, 14 men), diagnosed using DSM-IV criteria, 31 of
      their relatives (15 women, 16 men), and 34 control subjects (21 women, 13 men)
      were included in the study. The mean age of the patients, their relatives, and
      the control subects were 39.8 +/- 10.9, 58.1 +/- 12.5 and 37.3 +/- 17.0,
      respectively. The World Health Oranization Quality of Life-Brief Form was
      administered to all subjects. Quality of life was worse for the patient group
      than for their relatives and control subjects, but relatives of the patients and
      control subjects were not significantly different on Quality of life. Quality of
      life was negatively correlated with the severity of psychopathology and
      extrapyramidal side effects induced by antipsychotic drugs in the patients.

PMID- 15460377
TI  - Characteristics of work groups and their relationship with social and task
      cohesion in student teams.
AB  - Results of an exploratory study of relationships between work-group
      characteristics and the social and task cohesion of 18 business students engaged
      in team class projects. Regression analysis of scores on workload sharing, team
      spirit, task flexibility, and team cohesiveness for scales of the Work Group
      Characteristics Inventory indicated sharing of the workload was significantly
      associated with both task and social cohesion; team spirit with task cohesion but
      not social cohesion; and task flexibility with social cohesion but not task
      cohesion.

PMID- 15460378
TI  - Development and validation of a Client Problem Profile and Index for drug
      treatment.
AB  - The development of the Client Problem Profile and Index are described, and
      initial concurrent and predictive validity data are presented for a sample of 547
      patients in outpatient methadone treatment. Derived from the TCU Brief Intake for
      drug treatment admissions, the profile covers 14 problem areas related to drug
      use (particularly cocaine, heroin/opiate, marijuana, other illegal drugs, and
      multiple drug use), HIV risks, psychosocial-functioning, health, employment, and
      criminality. Analyses of predictive validity show the profile and its index
      (number of problem areas) were significantly related to therapeutic engagement,
      during-treatment performance, and posttreatment follow-up outcomes. Low moderate
      to high moderate effect sizes were observed in analyses of the index's
      discrimination.

PMID- 15460379
TI  - A comparative study of values and attitudes of inner-city and middle-class
      postpartum women.
AB  - This study compared postpartum women from the inner city (n = 94) and postpartum
      women from the urban middle class (n = 80) on values and goals for themselves and
      their newborn children. Terminal values of inner-city women for themselves
      related more to social and religious goals in contrast to the more intrapersonal
      and personal goals of middle-class women. Instrumental values of inner-city women
      for their newborn children demonstrated concern with conformity and control,
      whereas for the middle class there was more concern with competence. Goals for
      the near future of the inner-city mothers were based on a desire for jobs and
      education.

PMID- 15460380
TI  - Effects of a cognitive behavioral treatment protocol on the drop-out rates of
      exercise participants in 17 YMCA facilities of six cities.
AB  - The effects of a treatment system, based on tenets of cognitive behavioral and
      social cognitive theory, were estimated using case studies conducted in 17
      fitness facilities of six regional associations of the YMCA. Significant
      reductions in drop-out rates of new and returning exercisers were found for the
      treatment groups (ns=30 to 124; M drop out=38.9%, SD=9.5) compared to the control
      groups (ns=36 to 175; M drop out=62.9%, SD=6.4) over the 6-mo. times. Treatment
      effect sizes, by facility, ranged from small to large (phi=.10 to .43). Findings
      were consistent with previous research on earlier versions of the present
      treatment system conducted both within YMCAs and different fitness and wellness
      venues in the United States, United Kingdom, and Italy. Design limitations and
      the need for replication were discussed.

PMID- 15460381
TI  - Bryant's Empathy Index for children and adolescents: psychometric properties in
      the Spanish language.
AB  - The present study investigated the following issues: (1) the structure of
      Bryant's Empathy Index for children and adolescents in a Spanish sample of 408
      boys and 424 girls (M age=14.4 yr.), and (2) sex differences, including effect
      sizes and internal consistency of the scale. A principal components factor
      analysis with oblimin rotation showed that 20 of the index's 22 items load on
      three robust factors, related to Feelings of Sadness, Understanding Feelings, and
      Tearful Reaction with regard to the emotions of others. The 3-factor structure
      obtained an adequate fit to the data in the confirmatory factor analysis.
      Coefficients alpha ranged between .72 and .78. The 3 factors accounted for 42% of
      variance. As expected, girls scored higher than boys. It was concluded that the
      Spanish version of Bryant's Empathy Index has an acceptable reliability and
      construct validity, making it useful for research.

PMID- 15460382
TI  - Attachment representations in adults with congenital blindness: association with
      maternal interactive behaviors during childhood.
AB  - This study explores how maternal interactive behaviors experienced during the
      childhood of adults with congenital blindness are associated with their
      subsequent development and personality. Many researchers have found a high
      frequency of maternal directiveness and overprotection in sighted mother
      congenitally blind child relationships. One open question is whether these
      behaviors may have negative effects on congenitally blind children's subsequent
      development, or whether they may have a functionally adaptive-strategic role. The
      purpose of this study was to discriminate between the two hypotheses. This
      objective was pursued by adopting the theory of attachment and administering the
      Adult Attachment Interview to 15 participants with congenital blindness. Results
      suggested that directive and overprotective maternal behaviors are experienced by
      the persons with congenital blindness as encouraging and functional as long as
      they are accompanied by an affective, loving, and supportive attitude. Results
      did not support the hypothesis that directive and overprotective maternal
      interactive behaviors have a necessarily negative effect on the development of
      persons with congenital blindness.

PMID- 15460383
TI  - Affective components of the human-animal relationship in animal husbandry:
      development and validation of a questionnaire.
AB  - The aim of the present study was to identify the main dimensions of the human
      animal relationship in animal husbandry and to test the hypothesis of a coherent
      system linking attitudes and feelings. A second objective was to assess
      interindividual differences which could be linked to socioenvironmental or
      personal factors. The 26-item questionnaire was administered to 197 animal
      farmers (143 men, 54 women, 3.8% under 25 years old, 45.2% under 40 years, 44.2%
      under 60 years and 7.1% over 60 years). To include even farmers not in the
      official agricultural registries, we used a random selection procedure. A
      principal component analysis of responses followed by varimax rotation yielded
      two factors accounting for 30.7% of the total variance, a Friendship factor and a
      Power relationship factor. Significant differences on the Friendship factor were
      observed between groups by sex of farmers, education, size of the production
      system, and region of production. There were also differences on the Power
      relationship factor between groups by age and education. These results validate a
      questionnaire with 21 items, allowing measurement of positive and negative
      affects of farmers towards their animals.

PMID- 15460384
TI  - The Interpersonal Cognitive Distortions Scale: development and psychometric
      characteristics.
AB  - In this study, an Interpersonal Cognitive Distortions Scale was developed to
      assess cognitive distortions in individuals' interpersonal relationships. The
      sample comprised 425 university students. A factor analysis yielded three
      factors: Interpersonal Rejection, Unrealistic Relationship Expectation and
      Interpersonal Misperception. To examine construct validity the correlations
      between the scores on the Interpersonal Cognitive Distortions Scale and the
      Automatic Thoughts Scale (.54), the Irrational Belief Scale (.54), and the
      Conflict Tendency Scale (.53) were estimated. The first factor, the second
      factor, and the total scale discriminated married individuals who had low and
      high conflict intensity and conflict frequency. The reliability of the scale was
      estimated by performing a test-retest correlation (.74). Cronbach internal
      consistency coefficient alpha was .67.

PMID- 15460385
TI  - Flashbulb memories of personal events of 9/11 and the day after for a sample of
      New York City residents.
AB  - The present study assessed consistency of recollections of personal circumstances
      of the 9/11 World Trade Center attack and events of the day before (9/10), and
      the day after (9/12), in a sample of 100 New York City college students. The day
      before 9/11 represented an ordinary event. A questionnaire was administered
      twice, 1 wk. and 1 yr. after the 9/11 attack. Students were asked to describe
      their personal circumstances when hearing about the news of the World Trade
      Center attack and for the same time of day for 9/10 and 9/12. 18 students
      returned the follow-up questionnaire. Consistency of initial and follow-up
      responses for the central categories for both 9/11 and 9/12 of where, who, and
      activity was very high (9/11: "Where"--100%, "Who"--100%, "What"--94%; 9/12:
      "Where"--100%, "Who"--100%, "What"--80%). Recollections of 9/10 were
      significantly less consistent ("Where"--79%, "Who"--71%, "What"--71%). Analysis
      indicated that students formed vivid, consistent recollections during the events
      of both 9/11 and 9/12. It is likely that the events of 9/12 also became flashbulb
      memories, vivid recollections of traumatic events, because the emotional impact
      of the stressful events, i.e., police and military presence, disrupted schedules,
      relating to the 9/11 attack endured beyond the day of the attack.

PMID- 15460386
TI  - Self-esteem, authoritarianism, and democratic values in the face of threat.
AB  - This study investigated the associations among terrorist threat, right-wing
      authoritarianism, self-esteem, and their relations in support for democratic
      values. Students (n = 140) completed Altemeyer's Right-Wing Authoritarianism
      Scale, Rosenberg's Self-esteem Scale, and the Democratic Values Scale. The
      participants also read an editorial regarding the events of 9/11/01 and completed
      two mortality-salience questions to induce a sense of threat. Results showed that
      self-esteem was a significant contributor to the prediction of scores on the
      Democratic Values Scale. Furthermore, the interaction between self-esteem and
      right-wing authoritarianism explained significant variance in the Democratic
      Values Scale scores. The results are interpreted in light of theories addressing
      authoritarianism and self-esteem.

PMID- 15460387
TI  - Comparative prevalence of isolated sleep paralysis in Kuwaiti, Sudanese, and
      American college students.
AB  - A questionnaire measuring the incidence of isolated sleep paralysis was
      administered to 527 Kuwaiti, 762 Sudanese, and 649 American college students in
      what was the first study assessing the prevalence of isolated sleep paralysis in
      two Middle Eastern countries. Using the item "unable to move," 28.8% of Kuwaiti,
      29.9% of Sudanese, and 24.5% of American participants reported experiencing the
      disorder at least once. When a second item, "pressure to the chest," was also
      used, the respective percentages were 19.2%, 20.7%, and 11.4%. With both
      criteria, the Kuwaiti and Sudanese had a significantly greater prevalence than
      did the American students. The Kuwaiti and Sudanese students did not differ
      significantly from each other in the percentage who reported the symptoms.

PMID- 15460388
TI  - Trauma histories and attachment styles of members of the International Society
      for Traumatic Stress Studies.
AB  - The study is focused on the training, demographics, perceived emotional and
      physical health, past traumatic experience histories, and attachment styles of
      mental health professionals in the field of trauma (members of the International
      Society for Traumatic Stress Studies). While the data set is limited by a low
      response rate of 20%, the uniqueness of the sample and distinctive themes yield
      insight into the experience of trauma and its association with attachment style.

PMID- 15460389
TI  - Credit cues and impression management: a preliminary attempt to explain the
      credit card effect.
AB  - Prior research had suggested that individuals would estimate higher product
      values and even tip more in the presence of credit cues. In the absence of a
      clear theoretical interpretation of this credit card effect we propose that this
      tendency is an impression management strategy such that credit cue exposure
      influences perceptions of the self and focuses attention on individual wealth.
      Thus, in the presence of others, credit cues serve to enhance images of the self.
      Preliminary data in support of this alternative theoretical perspective are
      presented.

PMID- 15460390
TI  - Exploring the structure of Zuckerman's Sensation Seeking Scale, Form V in a
      Spanish sample.
AB  - The psychometric properties of the original version of the Sensation Seeking
      Scale (Form V) were analyzed in a sample of 1,006 Spanish university students.
      The total sample was randomly split into two halves. Exploratory factor analyses
      were conducted on the calibration sample (n=504), whereas confirmatory factor
      analysis procedures were performed on the validation sample (n=502). As previous
      studies have suggested, exploratory factor structure indicated that several items
      load on a different factor or have loadings lower than .30. Those problems were
      surpassed when the best five items per factor were factor analyzed again. The
      confirmatory factor analyses showed that a 4-factor simple structure model gave a
      clearly imperfect fit. A model of 20 items (5 items per factor) gave a better
      fit, although with similar problems regarding the low reliabilities of the
      Experience Seeking and Boredom Susceptibility subscales. The need for improvement
      of the four-factor structure is discussed.

PMID- 15460391
TI  - School children's responses on a semantic differential over a 10-year span.
AB  - A semantic differential scale was administered to 208 school children when they
      were in the second, fourth, sixth, eighth, tenth, and twelfth grades. Their
      perceptions towards two concepts were measured, Education (going to school) and
      Work (having a job). Each semantic differential scale had 15 adjective pairs and
      reflected the three underlying factors of Evaluative, Potency, and Activity.
      Because the study was conducted for 10 years (ages seven to 18), the changing
      cognitive developmental stages of the children were expected to influence factor
      analytic and reliability results. Confirmatory factor analysis, which forced the
      data into three factors, did not clearly identify the expected three factors,
      although more items loaded on the three factors with age. An exploratory factor
      analysis identified a trend across grades from six to four factors over time.
      Reliability also improved across age groups. Caution should be exercised when
      using the semantic differential with young children in investigations of abstract
      concepts.

PMID- 15460392
TI  - The relationship between personality and discretionary helping behaviors.
AB  - The relationship between personality and helping behaviors in three different
      contexts was examined in a field study. In a sample of 178 employees from three
      professional organizations, measures of the Big Five Personality factors were
      found to be related to discretionary helping behaviors performed in the context
      of one's home, workplace and the larger society. Collectively, the five
      personality factors accounted for 7% of the variance in Household Activities and
      Chores, 26% of the variance in Organizational Citizenship Behaviors and 10% of
      the variance in Volunteerism. Implications of these relations are discussed.

PMID- 15460393
TI  - Confirmatory factor analysis of the Sport Organizational Effectiveness Scale.
AB  - The purpose of this study was to examine the factorial validity of the 5-factor
      model of sport organizational effectiveness developed by Papadimitriou and
      Taylor. This questionnaire has 33 items which assess five composite effectiveness
      dimensions pertinent to the operation of sport organizations: calibre of the
      board and external liaisons, interest in athletes, internal procedures, long term
      planning, and sport science support. The multiple constituency approach was used
      as a theoretical framework for developing this scale. Data were obtained from
      respondents affiliated with 20 Greek national sport organizations with a
      questionnaire. Analysis indicated that the 5-factor model of effectiveness is
      workable in assessing the organizational performance of nonprofit sport
      organizations. The application of the multiple constituency approach in studying
      sport organizational effectiveness was also suggested.

PMID- 15460394
TI  - Health savings accounts and other account-based health plans.

PMID- 15460395
TI  - Stemming the patient tide: specific capacity management strategies can help
      hospital management better cope with crowded facilities.

PMID- 15460396
TI  - Nursing homes are hot commodities for all the wrong reasons.

PMID- 15460397
TI  - [Construction of tyrosine hydroxylase gene modified mesencephalic astrocytes].
AB  - OBJECTIVE: To construct tyrosine hydroxylase(TH) gene expressing mesencephalic
      astrocytes for the experiment of gene therapy for Parkinson's disease (PD).
      METHODS: The recombinant retroviral vector pN2ATH was constructed and transferred
      into PA317 pakaging cells by electroporation method. Resistant clones were
      obtained with G418 selective culture, and the virus supernatants were harvested.
      The mesencephalic astrocytes were cultured with the pN2ATH viral supernants.
      After 7-9 days culture, TH expression in the infected astrocytes were detected by
      immunohistochemistry. RESULTS: After G418 selection, high titer PA317/pN2ATH
      cells were obtained. The mesencephalic astrocytes transfected with pN2ATH
      succesfully expressed TH. CONCLUSION: Mesencephalic astrocytes transfected with
      pN2ATH can efficently express TH,which may provide a basis for further studies on
      gene therapy of PD in animals.

PMID- 15460398
TI  - [The effects of transferring DPC4-adenovirus on pancreatic adenocarcinoma cells].
AB  - OBJECTIVE: To observe the effect of transferring DPC4-adenovirus on pancreatic
      cells. METHODS: The recombined wild DPC4 gene and replication-deficiency
      adenovirus was transfected into cultured pancreatic adenocarcinoma cells and
      exograft pancreatic adenocarcinoma at the axillary flank of nude mice. The
      expression of objective gene was evaluated by flow cytometry and
      immunohistological chemistry assay. The cell cycle was also measured by flow
      cytometry. The related data were collected and analyzed with statistical methods.
      RESULTS: in viro, the suppression rate of transferring DPC4-adenovirus on
      cultured pancreatic adenocarcinoma cells was 30% on the fourth day. The
      fluorescence intensity of PD cells, P cells, HD cells, PA (Pc-3-Adenovirus) cells
      was higher than that of HS766T cells and HA cells (P<0.05). After transfection,
      PD cells proliferated most slowly, while H and HA proliferated most quickly
      (P<0.05). Significant difference was seen between the volume of exograft tumor of
      the controlled group and that of the treatment group (P<0.05). After
      transfection, the proliferation of cultured pancreatic adenocarcinoma cells was
      suppressed, the cells of G1 phase increased obviously (P<0.05) while the cells of
      S phase decreased (P<0.05), although no obvious increase of apoptosic cell number
      was observed. CONCLUSION: The DPC4-adenovirus can be transfected into pancreatic
      adenocarcinoma cells effectively. It could suppress the proliferation of
      pancreatic adenocarcinoma cells in vivo and in vitro.

PMID- 15460399
TI  - [Construction and expression of human alpha-fetoprotein recombinant plasmid].
AB  - OBJECTIVE: To construct AFP-expressing plasmid and study the expression in
      eukaryotic cells. METHODS: Total RNA was isolated from fetal liver tissue. Full
      length human AFP cDNA was obtained by RT-PCR amplification and then recombined
      into eukaryotic expression plasmid pcDNA3.1. The AFP sequence of the recombinant
      plasmid phAFP was determined. The AFP expressions in CHO transfected with phAFP
      and in muscle after injection phAFP were investigated by immunohistological
      methods. RESULTS: The restriction endonuclease mapping of recombinant plasmid
      showed 1.8 kb fragment as well as full-length human AFP cDNA, and the sequence is
      consistent with that from GenBank. The phAFP was successfully expressed in CHO
      and in muscle tissues. CONCLUSION: These results suggested that AFP can be used
      as a target gene of DNA vaccine in heptocellular carcinoma therapy.

PMID- 15460400
TI  - [The induction and function of dendritic cells from human cord blood with IFN
      alpha and GM-CSF in vitro].
AB  - OBJECTIVE: To probe into the possibility of obtaining dendritic cells (DCs) from
      human cord blood with rhIFN-alpha and rhGM-CSF. METHODS: The plastic adherent
      cells (monocyte-rich cells) from cord blood were cultured with rhGM-CSF and rhIFN
      alpha for 7 days. The morphological properties of DCs were observed by
      microscopy, the expression of CD83 and CD86 on DCs were determined by flow
      cytometry. The function of DCs stimulating allogeneic T lymphocyte proliferation
      was detected by MTT colorimetric method. RESULTS: After 7 days culture, some of
      the cultured cells acquired typical DC morphology and showed increased expression
      of CD83 and CD86. The yield of DCs attained its peak when the concentrations of
      rhIFN-alpha and rhGM-CSF were 600 U/ml and 2000 U/ml, respectively. When cultured
      cells (containing DCs) as stimulator cells were co-cultured with allogeneic T
      lymphocytes (effector cells) in different ratio, they could stimulate T cell
      proliferation remarkably, especially when the ratio of effector cells to
      stimulator cells was 20 to 1. CONCLUSION: Our findings suggest that cord blood
      adherent cells, when cultured with rhGM-CSF and rhIFN-alpha, can be induced into
      mature DCs with the function of stimulating allogeneic T cell proliferation.

PMID- 15460401
TI  - [Qualitative and quantitative analyses on the development of NKA-immunoreactivity
      in the esophagus of rats].
AB  - OBJECTIVE: To explore the expression and change of neurokinin A (NKA) in rat
      esophagus during development. METHODS: PAP immunocytochemistry method and image
      analysis were used to detect systematically the expression of NKA in rat
      esophagus from the 13th day of embryo to adult stage. RESULTS: In rat esophagus,
      the positive varicosities and fibres could be observed in the circular muscle
      layer and the muscularis mucosae layer at the 21st day before birth. With the
      development of rat digestive tract, the neurokinin A-immunoreactivity (NKA-IR)
      positive nerves could be observed gradually in the epithelium, submucosa,
      longitudinal muscle layer, myenteric plexus and submucosal plexus, while mature
      nerve fibres could be seen at one month after birth. The results of quantitative
      analysis are in accord with the developmental change of NKA-IR in esophagus.
      CONCLUSION: The ontogeny and development of NKA in rat esophagus proceeds from
      the last day before birth to 4 weeks after birth. NKA may play an important role
      in the development of rat esophagus.

PMID- 15460402
TI  - [The distribution of mast cells in benign and malignant prostate lesions and its
      biologic significance].
AB  - OBJECTIVE: To study the distribution profile of mast cells in benign and
      malignant prostate lesions and its biologic significance. METHODS: Fifty-three
      prostate specimens collected from 2000 through 2002 were examined, and the
      distribution of mast cells were analyzed. The paraffin sections were stained with
      anti-human mast cell tryptase immunohistologically. The numbers of cells stained
      with positive results in ten high-power fields were counted, and the mean was
      calculated. RESULTS: No significant relationship of mast cell distribution to
      inflammation in benign prostatic hyperplasias was observed. Significant
      differences between the mean mast cell numbers of intratumoral region and those
      of peritumoral region were noted (P<0.05). There was statistically significant
      difference in the mean mast cell numbers between well-differentiated groups and
      poorly-differentiated groups (P>0.05). CONCLUSION: There exists a relationship
      between prostate carcinoma tissue and mast cells. Mast cells may inhabit the
      tumor cells by different pathways.

PMID- 15460403
TI  - [Dendritic cells, natural killer cells and adhesion molecules in psoriasis].
AB  - OBJECTIVE: To study the role of the dendritic cells, natural killer cells and
      adhesion molecules play in the pathogenesis of psoriasis. METHODS: The expression
      levels of human leukocyte antigen (HLA)-DR, CD1a, CD16, CD57, tumor necrosis
      factor (TNF)-alpha and intercellular adhesion molecule (ICAM)-1 were detected by
      immunohistochemistry in lesions of 26 patients with psoriasis before and after
      treatment. RESULTS: The expression of HLA-DR, CD1a, CD16, CD57, TNF-alpha and
      ICAM-1 showed no significant difference between the active phase and the static
      phase of psoriatic lesions (P>0.05). After treatment, the positive expression of
      all markers decreased evidently or even disappeared with histopathological
      improvement in the resolvent phase of psoriatic lesions. There were statistically
      significant difference by Wilcoxon rank sum test (P<0.05). CONCLUSION: Dendritic
      cells, natural killer cells and adhesion molecules play an important role in the
      pathogenesis of psoriasis.

PMID- 15460404
TI  - [Study on glucocorticoid receptor alpha and beta in colonic mucosal cell of
      patients with ulcerative colitis].
AB  - OBJECTIVE: To investigate the relationship of the expression of GRalpha and
      GRbeta in the colonic mucosal cell of patients with ulcerative colitis to the
      efficacy of glucocorticoid (GC) therapy and the intensity of inflammation.
      METHODS: GRalpha expression and GRbeta expression in the colonic mucosal
      specimens were assessed by means of immunohistochemistry. Then comparative
      analyses were made on the GRalpha and GRbeta expression between the GC resistant
      group and GC sensitive group at various levels of inflammation. A normal response
      group was observed for comparison. RESULTS: The staining intensities of both
      GRalpha and GRbeta in colonic mucosal specimens showed significant differences
      between the GC resistant group, GC sensitive group and normal response group. No
      association between the expression of GRalpha and GRbeta and the degree of
      inflammation was found. CONCLUSION: These findings suggest that both GRalpha and
      GRbeta play an important role in the mechanism of the action of GC, and GRbeta
      functions as a dominant negative inhibitor of GRalpha in there. The expression of
      GRalpha and GRbeta in the colonic mucosal cell of patients with ulcerative
      colitis may serve as predictors of glucocorticoid response, but cannot be used as
      the markers of the severity of inflammation.

PMID- 15460405
TI  - [Expression of MCP-1 in airway of rats with COPD].
AB  - OBJECTIVE: To explore the role of monocyte chemoattractant protein-1 (MCP-1) in
      the pathogenesis of chronic obstructive plumonary disease (COPD). METHODS: Rat
      COPD model was established by exposing the rats to cigarette smoke daily. After
      COPD model was set up, bronchoalveolar lavage was performed. Total cell counts
      and alveolar macrophage (AM) counts in bronchoalveolar lavage fluid (BALF) were
      examined and the levels of MCP-1 and tumor necrosis factor-alpha (TNF-alpha) in
      BALF and serum were measured by ELISA. Lung tissue sections stained by HE were
      measured in terms of MLI, MAN and PAA by picture analysis system. RESULTS: MLI
      and PAA in COPD model were higher than those of control group while MAN was just
      on the contrary. Except MCP-1 levels in serum [(32.75 +/- 10.91) pg/ml vs (24.13
      +/- 6.92) pg/ml, P>0.05], MCP-1 levels, TNF-alpha levels, total cell counts and
      AM counts in BALF of COPD model group were significantly higher than those of
      control group (P<0.01). Positive correlations were demonstrated among MCP-1
      levels, TNF-alpha levels and AM counts in BALF in COPD group, but were not
      demonstrated between MCP-1 levels, TNF-alpha levels in serum and AM counts.
      CONCLUSION: There is a close correlation between MCP-1 in BALF and airway
      inflammation in COPD.

PMID- 15460406
TI  - [Expression of MOST-1 mRNA in bone marrow mononuclear cells from patients with
      acute lymphoblastic leukemia].
AB  - OBJECTIVE: To investigate the MOST-1 mRNA expression in bone marrow (BM)
      mononuclear cells in children with acute lymphoblastic leukemia, and to explore
      its association with immunophenotype and treatment response. METHODS:
      Semiquantitative RT-PCR was employed to study the MOST-1 mRNA expression in BM
      mononuclear cells separated by Ficoll density gradient method. The MOST-1
      expression levels were represented by the ratio of MOST-1 band pixels against its
      corresponding housekeeping gene beta-actin mRNA band pixels determined by GDS8000
      densitometry and GelWork-1 analysis software. The PCR product was eluted and
      sequenced, and its sequence was confirmed by Pairwise BLAST search. RESULTS: A
      total of 17 children with acute lymphoblastic leukemia were studied. MOST-1 mRNA
      was exclusively expressed in the mononuclear cells from 3 patients with ALL-L3
      type. However, there was no MOST-1 mRNA expression in other 14 children with ALL
      L1 or ALL-L2, irrespective of their initial peripheral WBC count and blast cell
      percentage in peripheral blood and bone marrow. The MOST-1 mRNA expression levels
      in two of the ALL-L3 patients with higher blast cell percentages in peripheral
      blood and bone marrow were 3- and 2-fold respectively as compared with that in
      the third ALL-L3 child with lower initial blast cell load. MOST-1 mRNA expression
      was no longer detected in the two ALL-L3 children after complete remission with
      combination chemotherapy. CONCLUSION: MOST-1 was expressed in the bone marrow
      mononuclear cells in patients with ALL-L3, and its expression level was somewhat
      related to tumor cell burden. It might be implicated in the leukemogenesis of ALL
      L3 and might serve as an indicator of tumor burden and thus a useful guide for
      clinical management.

PMID- 15460407
TI  - [Expression and clinical significance of cyclooxygenase-2 in medulloblastoma].
AB  - OBJECTIVE: To gain an insight into the possible relationship between the
      expression of cyclooxygenase-2 (COX-2) and the prognosis of the patients with
      medulloblastoma. METHODS: COX-2 expression was investigated in 52 medulloblastoma
      and 10 normal cerebellar tissue specimens by immunohistochemistry. Kaplan-Meier
      analyses, Log-rank test, and Cox proportional hazard model were used to explore
      the relationship between the percentage of COX-2 expression and the survival
      period of patients with medulloblastoma. RESULTS: Positive staining with COX-2
      was either moderately or strongly observed in most of the medulloblastoma
      (51/52). Moreover, COX-2 was expressed not only in tumor cells, but also in the
      vascular endothelial cells of tumor. No COX-2 immunoreactivity was observed in
      normal cerebellar tissue. Kaplan-Meier analyses demonstrated that high COX-2
      expression (> or = 50% of cells stained positive) correlated with poor survival
      for the study group as a whole (P < 0.0001). CONCLUSION: Our study provides
      evidence that COX-2 is expressed in the majority of medulloblastomas and that a
      potential role of COX-2 inhibitors as an adjuvant therapy for brain tumors may
      exist.

PMID- 15460408
TI  - [A study on the expression of Snap-25 mRNA in rat poisoned by tetramine].
AB  - OBJECTIVE: This study sought to reveal the relationship between Snap-25 and
      tetramine poisoning in order to approach the mechanism of tetramine poisoning.
      METHODS: The levels of Snap-25 mRNA in the brain tissues of poisoned SD rats were
      detected by RT-PCR method. RESULTS: After 1 hour of intoxication, the expression
      level of Snap-25 mRNA did not change in the rat brain. It increased at day 1 and
      reached its peak at day 3. The expression level of Snap-25 mRNA begain to descend
      at day 5, but it was still higher than that in the rat brain tissue of control
      group. CONCLUSION: In this study the expression of Snap-25 of rat poisoned by
      tetramine was not markedly increased in the early stage of poisoning, indicating
      that the symptoms of rat poisoned by tetramine are not induced by the changes of
      the Snap-25 level. The mechanism of high expression in Snap-25 mRNA probably
      involves the negative feedback of the body, which may increase the releasing of
      neurohumor and hence mitigate the symptoms of poisoning.

PMID- 15460409
TI  - [ER-alpha, IGF-1R expressions and co-expressions in newborn rats with
      experimental hypoxic-ischemic brain damage].
AB  - OBJECTIVE: To observe the distribution and change of insulin-like growth factor-1
      receptor (IGF-1R), estrogen receptor-alpha (ER-alpha) and their co-expression in
      the brains of normal newborn female rats and in the brains of those with hypoxic
      ischemic brain damage (HIBD). METHODS: The 7 day-old female SD rats were
      subjected to the ligation of right carotid artery (ischemia), then they were put
      into a box full with 8% oxygen and 92% nitrogen for an hour (hypoxia). The
      methods of immunohistochemistry and double-immunohistochemistry were used to
      detect the expression of IGF-1R, ER-alpha and their co-expression in the brain.
      RESULTS: (1) There were extensive immunoreactions of IGF-IR, ER-alpha in newborn
      rat's brain, and there were extensive co-localization of IGF-1R and ER-alpha in
      the same cells of cerebral cortex. (2) There were no changes in the expressions
      of IGF-1R and ER-alpha, no changes in the co-expression of IGF-1R and ER-alpha at
      24 hours of HIBD; whereas there were increasing expressions of IGF-1R, ER-alpha
      and increasing co-expression of IGF-1R, ER-alpha in the cerebral cortex on the
      7th day of HIBD. CONCLUSION: The above results suggest that there are co-action
      of IGF-1R and ER-alpha in the repair of hypoxic-ischemic brain damage.

PMID- 15460410
TI  - [TK locus mutation assay: comparison of L5178Y and TK6 cell lines].
AB  - OBJECTIVE: To compare the advantages and disadvantages of utilizing L5178Y and
      TK6 cell lines in the TK locus mutation assay. METHODS: The two cell lines were
      used for detecting and assessing the mutability of four chemicals (MMS, EMS, MMC
      and KCl); the microwell method of TK locus mutation assay was adopted. RESULTS:
      The two cell lines brought about similar results in the study. The tolerance of
      TK6 to all four chemicals was lower than that of L5178Y, and all the relative
      mutation indices of TK6 were higher than those of L5178Y. CONCLUSION: Each of the
      two cell lines has its own strong points; nevertheless, the authors recommend the
      applications of TK6 cell in the assay system since this cell line comes from
      human.

PMID- 15460411
TI  - [Study on the use of haemoglobin denaturation test as an alternative to Draize
      eye irritation test].
AB  - OBJECTIVE: To use haemoglobin denaturation test (HD test) as an alternative to
      Draize eye irritation test (Draize test). METHODS: Fourteen cosmetic ingredients
      were tested by HD test. The results were compared with two kinds of scores in
      Draize test, i.e. Maximum average Draize total score (MAS) and Score of 24 h
      after application (S24). RESULTS: The correlation coefficient between RDC50 and
      MAS and that between RDC50 and S24 were 0.926 and 0.921 respectively, while that
      between 1%lambdamax and MAS, and between 1%lambdamax and S24 were 0.881 and 0.791
      respectively. The results showed that RDC50 had a higher correlation with Draize
      test than 1%lambdamax did, but in the use of RDC50 some information of data would
      be lost. On the other hand, 1%lambdamax, which had a greater correlation with
      corneal score in the three component scores of the Draize test, could be used for
      assessing water-insoluble chemicals. CONCLUSION: The results showed that HD test
      could be used as an effective alternative to Draize eye irritation test.

PMID- 15460412
TI  - [A study on inflammatory regulation of human gallbladder epithelial cells by PPAR
      gamma ligand].
AB  - OBJECTIVE: To investigate the inflammatory regulation of human gallbladder
      epithelial cells (HGBEC) by peroxisome proliferator activated receptor gamma
      (PPAR-gamma) ligand ciglitazone. METHODS: HGBEC were cultured in medium
      containing human epidermal growth factor (hEGF). HIL-1beta were added into the
      ciglitazone groups and inflammatory control groups to make inflammatory model .
      IL-6 and TNF-alpha concentration in ciglitazone groups and all control groups
      were measured. RESULTS: HGBEC were cultured in medium successfully. The
      inflammatory model was made. The longest duration is 25 d. In inflammatory
      control groups, cells were edema with unclear cellular membrane and plasmid. In
      ciglitazone groups, the inflammatory edema of cells were less evident than that
      in inflammatory control groups, especially in 50 micromol/ml group. The IL-6
      concentration in ciglitazone groups is lower than that in control group (P<0.01).
      The relation between the inhibitory effect and the concentration of ciglitazone
      is positive correlation. CONCLUSION: Ciglitazone that can inhibit the
      inflammation of HGBEC maybe an effective treatment for acute and chronic
      cholecystitis.

PMID- 15460413
TI  - [Therapeutical effects of esculentoside A on rats with MsPGN induced by anti
      Thy1.1 antibody].
AB  - OBJECTIVE: To observe the therapeutical effects of esculentoside A (EsA) on rats
      with mesangial proliferative glomerulonephritis (MsPGN) induced by anti-Thy1.1
      antibody and make a comparison of the effects between EsA and dexamethasone
      (DXM). METHODS: Wistar rats with MsPGN induced by anti-Thy1.1 serum (ATS) were
      randomly divided into 3 groups: EsA group, DXM group, and model group. Moreover,
      a normal group was used for comparison. The BUN, SCr, urinary protein and renal
      pathological changes were examined after 7 d treatment with EsA and DXM. RESULTS:
      The urinary protein, cell count and mesangium area of glomerulus were
      significantly higher in all modeled groups than in normal group (P<0.001-0.05),
      and they were significantly lower in the treated groups than in untreated group
      (P<0.001-0.01). CONCLUSION: The results suggest that EsA is effective for
      reducing the urinary protein excretion and inhibiting the proliferation process
      of glomerular mesangium and matrix in rats with MsPGN.

PMID- 15460414
TI  - [Pharmacological action of pseudoephedrine salicylate on the central nervous
      system of mice].
AB  - OBJECTIVE: To study the action of pseudoephedrine salicylate on the central
      nervous system of mice. METHODS: Following the administration of pseudoephedrine
      salicylate at various dose levels and schedules, the alterations in general
      behavior and autonomic activities of the mice were recorded using photoelectric
      counter Type GJ-1, the changes in hypnotic action indices (sleep latency, sleep
      lasting time) for the mice placed on pentobarbital in advance were observed, and
      the muscular clonic spasm of forefoot and neck muscles as well as the deaths from
      convulsions induced by previously given pentylenetrazol, nicotin and picrotoxin
      were observed and recorded respectively. RESULTS: Pseudoephedrine salicylate
      (12.5, 25.0, 50.0, 100.0 mg/kg) administrated ip significantly inhibited the
      autonomic activities and the hypnotic action induced by previously given
      pentobarbital. Pseudoephedrine salicylate (100.0 mg/kg) given ip was noted to
      have synergistic effect on convulsions of the mice previously given
      pentylenetrazol and picrotoxin at subthreshold doses respectively, but no
      synergistic effect of pseudoephedrine salicylate (100 mg/kg) and nicotin (at
      subthreshold dose 0.018 mg/kg) was observed. CONCLUSION: Pseudoephedrine
      salicylate has excited effect on the central nervous system of mice.

PMID- 15460415
TI  - [The effect of propofol on isolated human pregnant uterine muscles].
AB  - OBJECTIVE: To investigate the effects of propofol on spontaneous contractions of
      isolated human pregnant myometrial smooth muscles. METHODS: Twenty isolated human
      pregnant myometrial muscle strips with rhythmic spontaneous contraction were
      randomly divided into two groups: control group (n=10) and propofol group (n=10).
      In propofol group propofol was added cumulatively. The changes of uterine
      contraction were monitored. RESULTS: Propofol at concentration of 0. 5 microg/ml
      and 2 microg/ml had no effect on the spontaneous contraction of isolated human
      pregnant uterine muscles; propofol at concentration of 5 microg/ml and 10
      microg/ml could significantly reduce the spontaneous contraction of isolated
      human pregnant uterine muscles; the higher the concentration was, the more would
      be the reduction. The effect could be blocked by oxytocin (140 +/- 50) microU/ml.
      CONCLUSION: Propofol could significantly reduce the spontaneous rhythmic
      contractions of isolated human pregnant myometrial smooth muscles in
      concentration-dependent manner. Oxytocin could antagonize the action.

PMID- 15460416
TI  - [Therapeutic effect of 125IUdR on the glioma cell line C6 in vitro and in vivo].
AB  - OBJECTIVE: To investigate the therapeutic effect of 125IUdR on gliomas. METHODS:
      By means of growth-curve, clonogenic formation experiment and MTT assay, the
      inhibitive effect of 125IUdR on the proliferation of C6 cells was studied in
      vitro. Wistar rats with intracerebral C6 gliomas were used to verify the
      therapeutic efficacy of 125IUdR in vivo. RESULTS: C6 monolayer cells were
      efficiently inhibited by 125IUdR in a time-and-dose-dependent manner. In the MTT
      assay, after treament with 150 kBq/ml 125IUdR for 5 days, the inhibition rate
      reached 93.06%. In murine transplantable tumor, 125IUdR had significant
      therapeutic effect on rats bearing solid tumor glioma C6. After treatment with
      125IUdR for 5 days, the tumor weight of experiment group was lower than that of
      blank group and control group (P<0.01). The median survival of animals treated
      with 125IUdR (27 days) was markedly longer than that of control group (9 days)
      (P<0.01). Na 125I and 127IUdR showed little inhibitive effect on the
      proliferation of C6 cells in vitro and in vivo. CONCLUSION: 125IUdR can markedly
      inhibit the growth of Glioma cell line C6. 125IUdR has potential for the
      treatment of malignant brain tumor.

PMID- 15460417
TI  - [Solitary fibrous tumor: the clinicopathologic and immunohistochemical
      characteristics of 26 cases].
AB  - OBJECTIVE: To study the clinicopathologic and immunohistochemical features of
      solitary fibrous tumor (SFT) and its biologic behaviour. METHODS:
      Clinicopathologic data of 26 cases were collected and analyzed. Among them,
      immunohistochemical staining (Envision method) for CD34, vimentin, CD99, bcl-2, S
      100, SMA, HBME-1, EMA and Ki67 were performed in 23 cases. RESULTS: The 17 male
      and 9 female patients were between 15 and 66 years of age (mean, 44). Their SFTs
      were located in nose and nasopharynx, cranial cavity, soft tissue, mediastinum,
      and parietal and visceral pleura. The main clinical manifestations were local
      mass and pressure symptom. The characteristic microscopic features included
      patternless growth pattern, alternating hyper- and hypo-cellular areas, blunt
      spindle cells within keloid-like hyalinization, and hemangiopericytoma-like
      regions. Positive immunohistochemical staining: vimentin 100%(23/23), CD34
      82%(19/23), bcl-2 87%(20/23), CD99 100%(23/23), SMA 30%(7/23). All cases were
      negative for S-100, HBME-1 and EMA. Follow-up information on 13 cases revealed
      that 3 patients had had relapse and died, the other 10 patients were alive
      without evidence of recurrence. CONCLUSION: SFT is a rare mesenchymal spindle
      cell tumor which may be found in various parts of human body and needs to be
      distinguished from other spindle cell tumors by differential diagnosis. The
      immunophenotype can be of help in this connexion. About 10% to 23% SFTs have
      malignant behaviour, manifesting as local recurrence or metastasis. The behavior
      of SFT is unpredictable, which requires careful, longterm follow-up.

PMID- 15460418
TI  - [Effects of the directions of an extraoral retractive force on the displacement
      of and stress distribution in palate].
AB  - OBJECTIVE: The aim of this study was to assess the effects of varying retractive
      force directions on the displacement of and stress distributions in palate.
      METHODS: A three-dimensional finite element model of the nasomaxillary complex
      was created, consisting of 1638 isoparametric elements and 1827 nodes. An
      extraoral retractive force of 9.8N was applied to the upper canines in 3
      different directions, i.e. parallel, 30 degrees upwards and downwards to the
      functional occlusal plane. Then we investigated the nature of stress
      distributions, the directions and amounts of displacement in palate by finite
      element analysis. RESULTS: In the midpalatal suture and transpalatal suture, all
      displacement directed to bone suture and increased gradually when the retractive
      force direction ranged from +30 degrees to -30 degrees. In the midmost part of
      palate, correlation between stress distributions and retractive force directions
      was not significant. Relatively compressive stresses were induced in the front
      and middle of the midpalatal suture, whereas nearly no stress was induced in the
      back. In the lateral part of palate, compressive stresses were nearly equal to
      tensile stresses in the front, while tensile stresses were induced in the middle
      and back. Meanwhile, there was no significant correlation between stress
      distributions and force directions. CONCLUSION: This study showed that the
      directions of retractive force had obvious effects on displacement but but little
      effect on stress distributions.

PMID- 15460419
TI  - [Interleukin-1beta and IL-1 receptor antagonist levels in gingival crevicular
      fluid and their relationship to clinical indices of periodontitis].
AB  - OBJECTIVE: To investigate Interleukin-1beta (IL-1beta) and IL-1 receptor
      antagonist (IL-1ra) concentrations in gingival crevicular fluid (GCF) of
      periodontally healthy teeth and to periodontitis teeth and to reveal their
      relationships to periodontal clinical indices. METHODS: Thirty GCF samples were
      harvested from periodontally healthy sites in which 15 samples were from
      periodontally healthy subjects and 15 GCF samples were from patients with chronic
      periodontitis, and 43 GCF samples (including 28 samples from BOP positive sites
      and 15 samples from BOP negative sites) were harvested from periodontitis sites
      of 33 patients with chronic periodontitis. Clinical indices (GI, PPD and CAL)
      were recorded for each tooth. The concentrations of IL-1beta and IL-1ra in GCF
      were quantified by ELISA method. RESULTS: (1) The mean concentrations of IL-1beta
      and IL-1ra and the average value of 10(4)IL-1beta/IL-1ra for periodontally
      healthy teeth were (61.891 +/- 20.719) pg/ml, (739.410 +/- 249.121) ng/ml and
      0.857 +/- 0.375, respectively. The mean concentration of IL-1beta (224.402 +/-
      87.416) pg/ml and the average value of 10(4)IL-1beta/IL-1ra for periodontitis
      teeth 6.813 +/- 0.375 were greater than those for healthy teeth, respectively
      (P<0.0001), and in contrast, the mean concentration of IL-1ra for periodontitis
      teeth (366.722 +/- 104.188) ng/ml was lower than that for healthy
      sites(P<0.0001). (2) For all sites, a strong inverse relationship was found
      between IL-1beta and IL-1ra levels in GCF (P<0.01). Both of IL-1beta and 10(4) IL
      1beta/IL-1ra values had positive correlations with GI, PPD and CAL (P<0.01). And
      the negative correlation was found between GI and IL-1ra (P<0.05). (3) The mean
      concentration of IL-1beta and the average value of 10(4)IL-1beta/IL-1ra at BOP
      positive teeth were greater than those at BOP negative teeth (P<0.0001), and the
      mean concentration of IL-1ra at BOP positive teeth was lower than that at BOP
      negative teeth (P<0.01). CONCLUSION: The results suggest that the increasing GCF
      level of IL-1beta and decreasing level of IL-1ra may be an important factor for
      the pathogenesis and development of chronic periodontitis and IL-1ra has an
      inhibitory effect on IL-1beta activity. The GCF level of IL-1beta and the value
      of 10(4)IL-1beta/IL-1ra, especially the latter one, are closely associated with
      the clinical indices of chronic periodontitis.

PMID- 15460420
TI  - [The effects of natural medicine on adherence of Streptococcus mutans to salivary
      acquired pellicle].
AB  - OBJECTIVE: To investigate the effects of 5 kinds of natural medicine such as
      Radix et Rhizoma Rhei on the adherence of Streptococcus mutans to salivary
      acquired pellicle, and to screen effective natural medicines for the prevention
      of caries. METHODS: The in vitro model of experimental pellicle was saliva-coated
      hydroxyapatites (S-HA). Streptococcus mutans and S-HA were treated with natural
      medicines respectively, and then the adherence of bacteria to S-HA was tested.
      RESULTS: Radix et Rhizoma Rhei, Semen Arecae and Rhizoma Liguistici Chuanxiong
      could decrease the attachment of Streptococcus mutans to S-HA, and Semen Arecae
      was the most effective one. Radix Angelicae Dahuricae had no remarkable effect,
      and Catechu inhibited the adherence only after the bacteria being under
      treatment. CONCLUSION: Radix et Rhizoma Rhei, Semen Arecae, Rhizoma Liquistici
      Chuanxiong and Catechu could effectively inhibit the adherence of Streptococcus
      mutans to salivary acquired pellicle, but the effect of Radix Angelicae Dahuricae
      on the adherence is un-noticeable.

PMID- 15460421
TI  - [Study on serum oxidized low density lipoprotein and anti-oxidized competence in
      patient with coronary heart disease].
AB  - OBJECTIVE: To analyze the serum oxidized low density lipoprotein (OX-LDL) and
      anti-oxidized competence in patients with coronary heart disease, and to explore
      the correlation between OX-LDL and atherosclerosis (AS). METHODS: The samples of
      fasting blood-serum were collected from 50 patients with coronary heart disease
      (CHD) and 50 normal controls with no cardiovascular disease, diabetes mellitus
      and nephrosis. The levels of triglyceride (TG), cholesterol (Chol), high density
      lipoprotein cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C),
      apoproteinA1 (Apo A1), apoproteinB100 (Apo B100), lipoprotein a (Lpa), OX-LDL,
      lipid oxidation (LPO) and anti-oxidized competence (AOC) were detected. RESULTS:
      The levels of TG, Chol, HDL-C, LDL-C, Apo B100 and NO were no difference between
      the patient with CHD and the normal controls (P>0.05). Lpa, OX-LDL and LPO were
      significantly higher than those of controls (P<0.05). ApoA1 and AOC were
      significantly lower than those of controls (P<0.01). CONCLUSION: There were no
      differences in respect to TG, Chol, HDL, LDL, Apo B100 between the CHD patients
      and normals, but OX-LDL was significantly higher than that of controls (P<0.05)
      and AOC was significantly lower than that of controls. These data suggest that OX
      LDL and AOC promise to find applications as more sensitive and valid markers for
      evaluating CHD.

PMID- 15460422
TI  - [Impact of cardiopulmonary bypass on free amino acid spectrum in plasma for
      patients with prosthetic valve replacement during the perioperative period].
AB  - OBJECTIVE: To investigate the impact of cardiopulmonary bypass (CPB) on free
      amino acid spectrum in plasma for patients with prosthetic valve replacement.
      METHODS: The concentrations of the free amino acid in plasma for 22 patients with
      prosthetic valve replacement were measured with pre-column derivatization of high
      performance liquid chromatography. RESULTS: Compared with the preoperative data,
      the concentrations of some free amino acid in plasma decreased after the
      operation of cardiopulmonary bypass (CPB), especially some of the glucogenic
      amino acid and branch chain amino acid decreased significantly (P<0.05).
      CONCLUSION: The operation of cardiopulmonary bypass (CPB) can decrease the
      concentrations of some free amino acid in plasma for patients with prosthetic
      valve replacement. It is essential to give these patients proper nutrition
      support during perioperative period.

PMID- 15460423
TI  - [Atherogenic index of plasma is associated with carotid intima-media thickness in
      patients with type 2 diabetes mellitus].
AB  - OBJECTIVE: To investigate the relationship of atherogenic index of plasma (AIP),
      an indirect indicator of LDL particle size, to carotid intima-media thickness
      (IMT) in patients with type 2 diabetes mellitus (T2DM) among Chinese Han
      nationality population. METHODS: One hundred and seventy-nine type 2 diabetic
      patients and 87 healthy subjects from a population of Chinese Han nationality
      were included. The AIP is the logarithmically transformed ratio of TG/HDL-c,
      which may serve as a surrogate method for assessing LDL particle size. The
      carotid IMT, as a surrogate continuous variable for macroangiopathy, was measured
      by B-mode ultrasonography in type 2 diabetic patients. The patients with T2DM
      were divided into three subgroups according to the IMT: IMT < or = 0.65 mm, 0.65
      mm < IMT < or = 1.1 mm and IMT > 1.1 mm. The Student-t test, one-way analysis of
      variance, univariate and multivariate analyses were implemented. RESULTS: (1) In
      T2DM group the values of triglyeeride (TG) and AIP were significantly higher than
      those in control group respectively, and the HDL-c value of T2DM group was
      significantly lower than that of control group. (2) There was significant
      difference in the age, body mass index (BMI), waist-hip ratio (WHR), the duration
      of DM, triglyceride (TG), total cholesterol (TC), LDL-c, HDL-c, HbAlc, TG/HDL-c
      and AIP among the three subgroups; the HDL-c value was inversely related to the
      IMT of T2DM, and all the other risk factors were positively related to the IMT of
      T2DM. (3) Multivariate analysis by linear regression showed that the value of AIP
      was an important risk factor in the pathogenesis and progress of IMT in patients
      with T2DM. CONCLUSION: AIP value, an indirect indicator of LDL particle size, is
      an important risk factor in pathogenesis and progress of IMT in patients with
      T2DM.

PMID- 15460424
TI  - [Body fat distribution: its characteristics and relationship to cardiovascular
      risk factors in obese Chinese].
AB  - OBJECTIVE: To investigate the distribution of body fat and analyze its
      characteristics and relationship with metabolic variables in obese Chinese.
      METHODS: In this observational, cross sectional study, the total body fat mass
      was measured using body mass index (BMI), and as an index of intra-abdominal fat
      accumulation, the ratio of the visceral (VA) to abdominal subcutaneous (SA)
      adipose area (VSR) was determined using a computed tomography (CT) scans made at
      the level of L4/L5 in 309 obese human subjects (male 88; female 221). Blood
      pressure (BP), fasting serum lipids such as triglycerides (TG), total cholesterol
      (TC), high density lipoprotein(HDL-c), low density lipoprotein (LDL-c), and serum
      uric acid (UA) were also determined. RESULTS: (1) There were no differences
      between the male and the female subjects in regard to age, BMI, SBP, LDL-c and
      HDL-c. SA was significantly greater in women, whereas VA and VSR were
      significantly greater in men; DBP, UA, TC and TG were significantly higher in men
      than in women. (2) In both men and women, VSR was significantly higher in obese
      Chinese than in obese European and Americans. Age, TG and LDL-c were higher in
      subjects with visceral fat obesity (VFO) than in those with subcutaneous fat
      obesity (SFO). In males, TC,UA were significantly higher in VFO than in SFO. (3)
      57 paired cases of male and female subjects matched for VSR were studied, and
      significant higher levels of serum UA and TG were noted in the male than in the
      female subjects. (4) After being adjusted for age and BMI, the analyses of
      partial correlation showed that in both men and women, VSR was positively
      correlated with TG and LDL-c, and SA was negatively correlated with LDL-c. In
      men, VA was positively correlated with SBP, and SA was negatively correlated with
      TG. In women, VA was positively correlated with TG, LDL-c; SA was negatively with
      LDL-c, but it was positively correlated with HDL-c and UA. (5) Stepwise multiple
      regression analysis showed that SA, VA, VSR were independent predictor for TG and
      LDL-c, SBP, and TC respectively (adjusting R2=0.079, 0.193, 0.122, 0.072,
      P=0.005, 0.000, 0.001, 0.007, respectively) in males. In females. VSR was an
      independent predictor for TG and LDL-c (adjusting R2=0.024, 0.113, P=0.012, 0.000
      respectively); both BMI and SA were important predictors for UA and HDL-c, and SA
      was an important predictor for SBP. CONCLUSION: The above data suggest that in
      obese Chinese, the body fat distribution is characterized by central obesity, the
      cardiovascular risk factors are not only associated with general obesity but more
      closely associated with regional body fat distribution (VFO), and the
      relationships between regional body fat distribution and metabolic variables vary
      with gender.

PMID- 15460425
TI  - [A follow-up study on dietary factors of kidney stones in Bao'an district,
      Shenzhen City].
AB  - OBJECTIVE: To evaluate the major dietary factors of kidney stones in Bao'an
      District of Shenzhen City and provide a scientific base for further effective
      prevention of kidney stones. METHODS: Following the process of stratified cluster
      random sampling in Bao'an district, a cross-sectional study (July-Aug, 2000) was
      conducted for collecting the base-line data on kidney stones from a population of
      permanent residents who were over 15 years old, exclusive of those who had had
      kidney stones or could not correctly respond to the questionnaire review. Then, a
      follow-up survey (July-Sept, 2002) for incident kidney stone cases was carried
      out among those residents. The methods for measurement included questionnaire and
      face-to-face interview, clinical examination and abdominal ultrasonography. All
      the investigators and interviewers were trained for the field work. And the data
      processing, dataset and analyses were performed using Visual-Fox 6.0 and SAS
      6.12. The risk factors of kidney stoned were comprehensively analyzed for
      dietary, life style, and family history of stones. The statistical analyses
      included case-control comparison, factor analysis, correlation analysis, cluster
      analysis and logistic regression. RESULTS: There were 305 kidney stones patients
      among 4552 follow-up members, the cumulative incidence of 2 years was 6.92%. The
      kidney stones were associated with the factors: menopause, RR=2.433; family
      history of stones, RR=1.544; sea foods, the RR (5-7 times/week vs < or = 1-2
      times/month) was 9.032; fruits, the RR (< or = 1-2 times/month vs > or = 1-2
      times/week) was 2. 249; sweet foods, the RR (5-7 times/week vs 1-2 times/week)
      was 2. 568; bean and bean products, the RR (5-7 times/week and < or = 1-2
      times/month vs 1-2 times/week) was 2.184 and 1.689. CONCLUSION: Changing the
      inappropriate habitual eating patterns and generalizing the use of proportioning
      dietary should be the main measures to prevent kidney stones.

PMID- 15460426
TI  - [Epidemiological analysis of polydactylies in Chinese perinatals].
AB  - OBJECTIVE: To investigate the epidemiologyical characteristics of polydactyly.
      METHODS: The method of Hospital-based surveillance within Chinese Birth Defects
      Monitoring Network (CBDMN) was adopted. All perinatals (from 28 weeks of
      gestation to a period of 7 days after birth) in the participating hospitals were
      investigated from 1996 to 2000. RESULTS: A total of 2097 cases were identified in
      2218616 perinates, the prevalence was 9.45 per 10000. The prevalence of male was
      significantly higher than the female's. The urban prevalence was 9.60 per 10000,
      and the rural prevalence was 9.05 per 10000. Significant difference and
      increasing time trend were observed in annual prevalence rate during 1996-2000.
      Of the 2097 cases, 1853 (88.4%) were in the isolated form, and the rest (11.6%)
      of them were combined with other defects. Among 1942 perinatals affected by
      polydactyly, 679 (34.96%) cases occurred in the left limbs, 886 (45.62%) cases
      occurred in the right limbs, and 377 (19.41%) cases occurred bilaterally.
      CONCLUSION: The prevalence rates of polydactylies in Chinese perinatals show male
      predominance and geographic variations. Most of the polydactyly cases were in the
      from of single defect; however, those accompanied by other defects had a higher
      perinatal fatality rate.

PMID- 15460427
TI  - [Study on the determination of piperazinylethylestrone].
AB  - OBJECTIVE: To establish an HPLC method and a non-aqueous titration for the
      determination of piperazinylethylestrone drug substance, and an HPLC method for
      the determination of piperazinylethylestrone in dog plasma. METHODS: Anhydrous
      acetic acid as solvent, 0.1 mol/L perchloric acid as titrant, crystal violet
      solution as indicator to establish non-aqueous titrations and ODS column as
      stationary phase, methanol and a mixture of 0. 025 mol/L sodium phosphate
      monobasic and 0.02 mol/L sodium dedecyl sulfate (80:20) [adjusted with phosphoric
      acid to a pH (4.8 +/- 0.1)] as mobile phase, 220 nm as detective wavelength to
      establish HPLC-UV method for determination of piperazinylethylestrone drug
      substance; FMOC-CL as a derivatization reagent, FD as a detector to establish an
      HPLC method with derivatization and column switching for determination of
      piperazinylethylestrone in dog plasma. RESULTS: The RSD of non-aqueous titrations
      within-day and between-day were 0.28% and 0.21%, respectively; the established
      HPLC-UV method had good linearity and precision within the range of 1.001-5.005
      microg of piperazinylethylestrone, the detection limit was 4 ng (S/N=3); the
      linearity of HPLC method with derivatization and column switching was within the
      range of 8.4-420 ng/ml, the detection limit was 1 ng (S/N=3). The clean-up
      recoveries were from 77.24% to 83.10%, and the method recoveries were 98.33%
      103.3%. The RSD of within-day and between-day were less than 7.7% and 7.3%,
      respectively. CONCLUSION: The above three methods are simple, accurate and
      precise for the determination of piperazinylethylestrone drug substance and for
      the determination of piperazinylethylestrone in dog plasma.

PMID- 15460428
TI  - [A new approach to protein phosphorylation modification analysis for neuron].
AB  - OBJECTIVE: To develop a new method for analysis of protein phosphorylation
      modification in cultured neuron. METHODS: Cultured neurons were pre-incubated in
      DMEM without sodium phosphate for 15 min to deplete the metabolic pools. Neurons
      were then labeled with [32P] orthophosphate (2.78 x 10(6) Bq/ml) for 1.5 h and
      stimulated by either insulin (100 nmol/L), EGF (20 nm/L) or saline for 0, 5, 20,
      60, 120 min. Reactions were terminated by freezing neurons in liquid nitrogen
      prior to the solubilizing of them in a lysis buffer containing 8 mol/L urea, 4%
      CHAPS, 2% Bio-lyte, pH 3-10, 2 mmol/L TBP. Protein concentrations were determined
      with Bio-Rad DC Protein Assay kit. The 32P-labled lysates isoelectrically focused
      on IPG Drystrip pH 3-10 or pH 4-7 Linear gels were subsequently separated in
      second-dimensional SDS-PAGE. The dried gel was autoradiographed for 5 days at -70
      degrees C with an intensifying screen. Alternatively, the separated proteins were
      visualized by Coomassie Brilliant Blue (CBB) R250 straining. RESULTS:
      Autoradiography of the 2-DE-separated 32P-laebled neuron lysates revealed around
      100 phosphoproteins. This phosphoprotein pattern was stable at 1.5 h after
      radiolabelling and did not vary significantly for up to 4 h further incubation in
      the absence of hormone. Most of the major proteins which are phosphorylated in
      response to insulin or EGF migrated with pH 4.6-6.5 and MW 20000-130000. Insulin
      and EGF induced similar but not identical patterns of protein phosphoryltion in
      neurons. Only a few phosphoproteins were abundant enough to be visualized by CBB
      straining, suggesting that abundance of these phosphoproteins is extremely low.
      Responses to both isulin and EGF are marked by more increased labeling of the
      constitutive phosphoproteins, compared with the appearance of new
      phosphoproteins. CONCLUSION: This approach co-application of 32P-labeled with 2
      DE separation and autoradiography has proven to be specific and sensitive in
      phosphoprotein analysis for neuron. It was valuable in functional proteomic
      analysis for protein phosphorylation modification during cellular signal
      transduction.

PMID- 15460429
TI  - [Effects of Evan Blue on perfused dimension display and rabbit left ventricular
      action potential].
AB  - OBJECTIVE: Simultaneous recording of transmembrane action potential at
      endocardium, midcardium and epicardium and transmural ECG in arterially perfused
      left ventricular preparation is a new method for researching into the mechanism
      about ventricular arrhythmia, and in this connection, how to distinguish the
      perfused area plays a key role in keeping preparations under normal condition.
      This study is aimed to evaluate the effects of Evan Blue on the displaying of the
      perfused area and on the characters of transmembrane action potential of the
      arterially perfused left ventricular preparations. METHODS: Rabbit left
      ventricular wedge preparations were perfused with Tyrode solution continuously
      via left circumflex, and the action potential of endocardium, midmyocardium,
      epicardium or transmural electrocardiogram were recorded simultaneously. The
      action poatential duration (APD), transmural dispersion of repolarization (TDR)
      or QT intervals were compared and the color variation of the preparations were
      studied before and 30 min after perfusion with Evan Blue. RESULTS: Under the
      basic stimulatory cycle length of 1000, 2000, 4000 ms, there was no significant
      difference of APD in the same transmural layer or TDR before and after Evan Blue
      perfusion (P<0.01), but APD or TDR stimulated at basic cycle length of 1000-4000
      ms were all higher than those recorded at 500 ms (P<0.01); APDs of endocardium
      were much longer than those of epicardium or midmyocardium (P<0.01); there was no
      significant difference in APD, TDR and QT intervals before and after Evan Blue
      perfusion (P>0.05). No premature ventricular contractions and ventricular
      tachycardia happened during the experiments. CONCLUSION: Evan Blue can be used as
      a marker to identify the perfused area.

PMID- 15460430
TI  - [Mesorectal spread and circumferential margin involvement of rectal cancer
      studied on large slice].
AB  - OBJECTIVE: To provide the mode of cancer distribution in the mesorectum and
      circumferential resection margin. METHODS: Large slice technique was used in the
      pathologic study of 62 specimens operated on following the principles of total
      mesorectal excision (TME). RESULTS: More than 40% of all the observed neoplastic
      foci were located in the outer layer of the mesorectum in Stage III patients.
      Further analysis of the foci's localities with respect to the primary tumor's
      locality showed that ipsolateral neoplastic foci (44.44%) were significantly more
      than the contralateral neoplastic foci (13.33%) in the mesorectum (P<0.05).
      Extramural distal spread was found in 8 cases with the maximum extent of 3.5 cm.
      No significant difference in occurrence of circumferential margin involvement
      (CMI) was observed among tumors of different location, but tumors of poorer
      differentiation were noted to have a higher risk of CMI. CONCLUSION: Large slice
      technique offers a whole image of rectum, mesorectum, together with the position
      of neoplastic foci. There are outer preponderance and lateral discrepancy of
      neoplastic foci distribution in the mesorectum. A distal clearance margin of 4 cm
      would be mandatory. We advocate the adoption of TME as the baisc surgical
      principles in treating patients with rectal cancer and in avoiding surgery
      related circumferential margin involvement.

PMID- 15460431
TI  - [Management of the rectovaginal fistula. A review of five years at the Colon and
      Rectal Unit of the General Hospital of Mexico City].
AB  - BACKGROUND: Rectovaginal fistula, although infrequent, produces considerable
      discomfort to the patients and disables them in their social life. OBJECTIVES: To
      review and report the experience in the management of rectovaginal fistula in the
      Colon and Rectal Unit of the General Hospital of Mexico City, from January 1997
      to December 2001. MATERIAL AND METHODS: A retrospective, observational and
      descriptive study was designed including all patients diagnosed with rectovaginal
      fistula, who had not been previously operated for this condition in the Colon and
      Rectal Unit of the General Hospital of Mexico City from January 1977 to December
      2001. RESULTS: Thirty-eight patients were included, aged between 17 and 70 years
      with a mean age of 24. The etiology of the rectovaginal fistulas was: obstetric
      trauma in 21 patients (55.2%), post-surgical in 5 (13.1%), traumatic in 5
      (13.1%), after radiotherapy in 5 (13.1%) and malignant in 2 (5.2%). DISCUSSION:
      Rectovaginal fistula treatment relies on fistula classification (simple or
      complex), its location, and damage or not to the sphincter mechanisms and prior
      surgical repair. CONCLUSIONS: The most frequent surgical approach was the
      creation of a fourth degree perineum laceration and reconstruction (45.7%),
      followed by the advancement flap (25.7%). Complex fistulas were handled with a
      stoma. The surgical approach of rectovaginal fistula must rely on etiologic,
      anatomic and physiologic basis.

PMID- 15460432
TI  - [Vulvar metastatic disease: experience at the National Institute of Cancer of
      Mexico].
AB  - BACKGROUND: Malignant vulvar tumors account for less than 1% of the malignant
      lesions in women and between 3 to 5% of the malignant tumors from female genital
      tract. The most common malignant neoplasia is squamous cell carcinoma followed by
      melanoma and in last place sarcomas and metastasis. OBJECTIVE: To report the
      incidence and experience at the Instituto Nacional de Cancerologia of Mexico.
      MATERIAL AND METHODS: Vulvar metastasis were recorded from the files of pathology
      department of the Instituto Nacional de Cancerologia diagnosed from 1984 to 2002.
      Clinical and histological characteristics from these cases were evaluated as well
      as clinical behavior. RESULTS: Eight cases of vulvar metastasis were found from a
      total of 436 malignant vulvar neoplasias (1.8%). Primary tumor in six cases was
      located in genital area; in the other two the primary tumor was located in breast
      and bladder. Labium majus was the most frequent site of metastasis. All the
      patients died with disease progression in a period of one month to one year after
      the diagnosis of vulvar metastasis. CONCLUSION: Vulvar metastasis is a rare
      phenomenon; these lesions are in relation to advanced clinical stage and a poor
      prognosis.

PMID- 15460433
TI  - [Effectiveness of a clinimetric scale for diagnosing vulvovaginal candidosis].
AB  - BACKGROUND: Vulvovaginal candidosis is one of the most frequent infections of the
      female genital system. It is believed that 75% of women in reproductive life have
      suffered from vulvovaginal candidosis at least once in their life. OBJECTIVE: To
      evaluate the effectiveness of a clinimetric scale based on clinical
      characteristics and factors of risk to diagnose vulvovaginal candidosis and to
      establish the cut points. MATERIAL AND METHODS: A questionnaire was elaborated by
      means of consensus, there were questions about symptoms and risk factors for the
      diagnosis. It was applied to women in reproductive age, besides the
      cervicovaginal culture. The resulting questionnaire was evaluated by means of the
      analysis of sensitivity according to the criteria of Feinstein. The determination
      of points of cut was made by means of curves ROC as well as sensitivity,
      specificity, positive and negative predictive value. The univariable analysis was
      made by means of the test of chi2 and the exact test of Fisher. We used
      likelihood ratio for association of variables and the multi-variate logistic
      regression analysis was made to fit variable potentials. RESULTS: One-hundred
      forty-two women answered the questionnaire, 39 (27%) had positive isolation to
      Candida. Vulvar edema (3.49 OR IC 95% 1.16-10.43 p = 0.02) and ardor (OR 2.40 IC
      95% 0.88-6.51 p = 0.08) were significant. None of the risk factors were
      statistically significant. It was reported with sensitivity of 76%, specificity
      of 38%, VPP 32% and VPN 81% for the = 60 record. CONCLUSION: The clinimetric
      scale is brief, valid and easy to apply. It can be used independently of the
      educative or cultural factors that limit the accomplishment of other forms of
      diagnosis, such as the vaginal flow exam and the cervicovaginal culture.

PMID- 15460434
TI  - [Mechanical changes of the detrusor after antiincontinence surgery].
AB  - BACKGROUND: Stress urinary incontinence is secondary to an intrinsic defect in
      the closure or a lack of urethral support; the treatment is surgical and this may
      affect vesical voiding by creating an obstruction, modifying the contraction
      power at opening and the mechanical properties of the detrusor. OBJECTIVES: To
      know if there are changes in the contractile characteristics of the detrusor in
      order to maintain an efficient voiding after surgical correction of the urinary
      incontinence. MATERIAL AND METHODS: This was a cohort study of the urodynamic
      variables, mechanical work and energy of the detrusor, during cystometric and
      pressure-flow analysis, before and after antiincontinence surgery. Forty-five
      patients were included with urodynamic study before surgery and another one
      between 6 weeks and 6 months. We analyzed these data using student T test and
      ANOVA. RESULTS: The average and maximum flow rates, voiding efficient and
      velocity of the detrusor decreased. The pressures of the detrusor, the opening
      power and energy increased significantly after the surgery. These changes were
      more important in the Burch group. The 24.4% of the patients presented de novo
      hyperactive bladder; before surgery these patients had detrusor's pressures,
      voiding power and energy significantly greater. CONCLUSION: There are changes in
      the mechanical properties of the detrusor after antiincontinence surgery; the
      detrusor needs a greater energy output to defeat urethral resistance and to
      maintain the vesical voiding, these were better in patients with Burch procedure
      and with overactive bladder.

PMID- 15460435
TI  - [Acrosomic reaction of human spermatozoid demonstrated with clorotetracycline].
AB  - BACKGROUND: Sperm preparation and acrosomic reaction have been largely studied to
      explain the physiology of sperm as reproductive cell. OBJECTIVE: To identify the
      morphological changes on in vitro prepared human sperm cells and in spontaneous
      and ionophore A23187 induced acrosome reaction of infertile males, through the
      application of the chlortetracycline test. DESIGN: Experimental prospective
      study. MATERIALS AND METHODS: Sperm samples of 17 subfertile males were processed
      as routine for a sperm analysis, we carried out sperm preparation and induction
      of the acrosomic reaction by means of calcium ions A23187. The prepared sperm
      with direct swim-up was assessed at one hour and at four hours. Direct aliquots
      were taken and processed for the test with CTC, we considered as positive result
      obtaining more than 15% increase in the induced AR versus spontaneous. RESULTS:
      The whole population was classified as asthenozoospermic. Eight training
      morphological patterns were identified and we found four types of responses for
      the induced AR: Type I had an increase at one and at four hours incubation (47%);
      type II had an increase only after 1 hour incubation (23.5%); type III had an
      increase only at 4 hours incubation (17.7%), and type IV did not have increase
      (11.8%). CONCLUSION: These results suggest that in astenozoospermic patients the
      training process has variations during the incubation time, demonstrated by the
      response at A23187. These findings could let us to select better spermatozoa in
      this group of males at the moment when capacitance is actually attained, thus
      being able to carry out more effective techniques in assisted reproduction.

PMID- 15460436
TI  - [Heterosexual precocious puberty due to arrhenoblastoma. Postsurgical spontaneous
      pregnancy].
AB  - It is presented the case of a female with heterosexual precocious puberty
      associated to hyperandrogenism and virilization due to arrhenoblastoma, who
      became pregnant after surgery. Clinical study: a 14-year-old female initiated at
      age 6 years with premature pubarche and telarche. By age 11, the patient only had
      one menstrual period along with virilization. Physical exam disclosed: facial
      acne, cricoid enlargement, breast Tanner II, pubic hair Tanner III, clitoromegaly
      of 4.5 cm and hypotrophy of labia majora. Ferriman and Gallwey: 12. Basal
      quantitation of circulating testosterone: 1.25 ng/mL (normal: 0.2 to 0.8 ng/mL),
      androstenedione 13.9 ng/mL (normal: 0.5 to 2.4 ng/mL). A pelvic ultrasonographic
      study showed: uterus of 66 x 25 x 30 mm, right ovary of 50 x 50 mm, hyperechoic
      with echolucid and nodular areas (vol. 65.3 cc). Left ovary was of 30 x 30 mm
      with echolucid areas of 2.0 mm (vol. 5.1 cc). Cariotype: 46XX. Surgical right
      oophorectomy was performed containing an ovoid tumor of 4 x 3 x 3 cm. Histologic
      analysis revealed a Sertoli Leydig (Type II, Mayoer) cell tumor. The patient
      resumed menses and became pregnant at age 20 (22 week obitus). In the last
      assessment, performed 6 years after surgery, the patient resumed normal menses,
      Ferriman and Gallwey 5, Tanner V and regression of clitoromegaly to 3.0 cm. In
      this case, surgery provided remission of hyperandrogenism, normal menstrual
      cycles and fertility restoration.

PMID- 15460439
TI  - Solid phase synthesis of 3-(4-hydroxyphenyl)coumarin: preliminary experiments for
      combinatorial synthesis of substituted 3-phenylcoumarin derivatives.
AB  - Coumarin and its derivatives occur widely in nature. Many attempts were made for
      synthesis of various coumarin derivatives because of their interesting biological
      activities. In this study, solid phase synthetic approach of 3-(4
      hydroxyphenyl)coumarin was achieved for combinatorial synthesis of substituted 3
      phenylcoumarin analogues. Starting from 4-hydroxyphenylacetic acid methyl ester,
      release of 3-(4-hydroxypnehyl)coumarin from polymer support was accomplished.

PMID- 15460440
TI  - Synthesis of new diselenide compounds as anti-inflammatory agents.
AB  - Many diselenide compounds are used as antioxidants, enzyme inhibitors and
      cytokine inducers. Three new diselenide compounds, bis-(2-hydroxyphenyl)
      diselenide, bis-(3-hydroxyphenyl) diselenide and bis-(4-hydroxyphenyl) diselenide
      were designed and synthesized as anti-inflammatory agent. All of them were found
      to have strong in vitro activity in anti-inflammatory assays.

PMID- 15460441
TI  - Optical purity determination of (S)-ibuprofen in tablets by achiral gas
      chromatography.
AB  - An optical purity test was indirectly performed on (S)-ibuprofen as its
      diastereomeric (R)-(+)-1-phenylethylamide derivative using achiral gas
      chromatography (GC). The method for the determination of trace (R)-ibuprofen
      (optical impurity), within the range 1.0 to 50 ng, from a racemic ibuprofen
      standard was linear (r = 0.9997) with acceptable precision (% RSD < or = 5.3) and
      accuracy (% RE = 0.7 - -3.9). Similar results were obtained with the method
      validation for the quantification of (S)-ibuprofen within the range 0.1 to 2.0
      microg using a (S)-ibuprofen standard. When applied to seven different commercial
      (S)-ibuprofen products, their optical purities (98.7 - 99.1%) were determined
      with good precision (% RSD < or = 4.0).

PMID- 15460442
TI  - Triterpenoids from Acanthopanax koreanum root and their inhibitory activities on
      NFAT transcription.
AB  - Two triterpenoids (1,4) and two triterpenoid glycosides (2,3) were isolated from
      the root of Acanthopanax koreanum (Araliaceae). Their structures were identified
      as impressic acid (1), acankoreoside A (2), 3-epi-betulinic acid 28-O-[alpha-L
      rhamnopyranosyl(1 --> 4)-beta-D-glucopyranosyl(1 --> 6)]-beta-D-glucopyranosyl]
      ester (3), and ursolic acid (4) by physicochemical and spectroscopic methods. Of
      these compounds, impressic acid (1) exhibited a potent inhibitory activity
      against NFAT transcription factor (IC50: 12.65 microM).

PMID- 15460443
TI  - Cytotoxicity and DNA topoisomerases inhibitory activity of constituents from the
      sclerotium of Poria cocos.
AB  - The bioactivity-guided fractionation of the methylene chloride extract of the
      sclerotium of Poria cocos led to the isolation of (S)-(+)-turmerone (1),
      ergosterol peroxide (2), polyporenic acid C (3), dehydropachymic acid (4),
      pachymic acid (5), and tumulosic acid (6). Compounds 4-6 exhibited moderate
      cytotoxicities, with IC50 values of 20.5, 29.1, and 10.4 microM, respectively,
      against a human colon carcinoma cell line. However, 3-6 not only showed
      inhibitory activities as potent as etoposide used as a positive control on DNA
      topoisomerase II (36.1, 36.2, 43.9 and 66.7% inhibition at a concentration of 20
      microM, respectively), but also inhibition of DNA topoisomerase I (55.8, 60.7,
      43.5, and 83.3% inhibition at a concentration of 100 microM, respectively).

PMID- 15460444
TI  - Ginsenoside Rh2 induces apoptosis via activation of caspase-1 and -3 and up
      regulation of Bax in human neuroblastoma.
AB  - In human neuroblastoma SK-N-BE(2) cells undergoing apoptotic death induced by
      ginsenoside Rh2, a dammarane glycoside that was isolated from Panax ginseng C. A.
      Meyer, caspase-1 and caspase-3 were activated. The expression of Bax was
      increased in the cells treated with ginsenoside Rh2, whereas Bcl-2 expression was
      not altered. Treatment with caspase-1 inhibitor, Ac-YVAD-CMK, or caspase-3
      inhibitor, Z-DEVD-FMK, partially inhibited ginsenoside Rh2-induced cell death but
      almost suppressed the cleavage of the 116 kDa PARP into a 85 kDa fragment. When
      the levels of p53 were examined in this process, p53 accumulated rapidly in the
      cells treated early with ginsenoside Rh2. These results suggest that activation
      of caspase-1 and -3 and the up-regulation of Bax are required in order for
      apoptotic death of SK-N-BE(2) cells to be induced by ginsenoside Rh2, and p53
      plays an important role in the pathways to promote apoptosis.

PMID- 15460445
TI  - Isolation of epi-oleanolic acid from Korean mistletoe and its apoptosis-lnducing
      activity in tumor cells.
AB  - A triterpene was isolated as a cytotoxic principle from the dichloromethane
      extract of Korean mistletoe (KM; Viscum album coloratum) by repeated silica gel
      chromatography and recrystallization. In in vitro analysis of cytotoxic activity
      using various human and murine tumor cell lines, the dichloromethane extract of
      KM was highly cytotoxic against these cells. We isolated the most active
      compound, referred to VD-3, from the dichloromethane extract of KM. The VD-3 was
      shown to be less cytotoxic to normal cells (murine splenocytes). From the
      identification of the chemical structure of VD-3 by spectral data and chemical
      synthesis, the compound was proven to be epi-oleanolic acid. Tumor cells treated
      with VD-3 showed a typical pattern of apoptotic cell death, such as apparent
      morphological changes and DNA fragmentation. These results indicate that epi
      oleanolic acid is an important compound responsible for antitumor activity of KM.

PMID- 15460446
TI  - Capsaicin-induced apoptosis of H-ras-transformed human breast epithelial cells is
      Rac-dependent via ROS generation.
AB  - Many studies have focused on the anticarcinogenic, antimutagenic or
      chemopreventive activities of capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide)
      which is a major pungent ingredient in red pepper. We have previously shown that
      capsaicin selectively induces apoptosis in H-ras-transformed MCF10A human breast
      epithelial cells but not in their normal cell counterparts (Int. J. Cancer, 103,
      475-482, 2003). In this study, we investigated the possible roles of reactive
      oxygen species (ROS) and Rac1 in capsaicin-induced apoptosis of H-ras MCF10A
      cells. Selective induction of ROS generation by capsaicin treatment was observed
      only in H-ras MCF10A cells. Pretreatment of H-ras MCF10A cells with an
      antioxidant N-acetylcysteine (NAC) significantly reversed capsaicin-induced
      growth inhibition, suggesting that ROS may mediate the apoptosis of H-ras
      transformed cells induced by capsaicin. Rac1 was prominently activated by H-ras
      in MCF10A cells. Based on the studies using a wild type Rac1 and a dominant
      negative Rac1 constructs, we propose that Rac1 activity is critical for
      inhibitory effect of capsaicin on growth of H-ras-transformed MCF10A cells
      possibly through ROS generation.

PMID- 15460447
TI  - Tissue transglutaminase is not involved in the aggregate formation of stably
      expressed alpha-synuclein in SH-SY5Y human neuroblastoma cells.
AB  - Intraneuronal deposition containing alpha-synuclein is implicated in the
      pathogenesis of synuclein-opathies including Parkinsons disease (PD). Although it
      has been demonstrated that cytoplasmic inclusions of wild type alpha-synuclein
      are observed in the brain of PD patients and that alpha-synuclein mutations such
      as A30P and A53T accelerate aggregate formation, the exact mechanism by which
      alpha-synuclein forms insoluble aggregates is still controversial. In the present
      study, to understand the possible involvement of tissue transglutaminase (tTG) in
      aggregate formation of alpha-synuclein, SH-SY5Y cell lines stably expressing wild
      type or mutant (A30P or A53T) alpha-synuclein were created and aggregate
      formation of alpha-synuclein was observed upon activation of tTG. The data
      demonstrated that alpha-synuclein negligibly interacted with tTG and that
      activation of tTG did not result in the aggregate formation of alpha-synuclein in
      SH-SY5Y cells overexpressing either wild type or mutant alpha-synuclein. In
      addition, alpha-synuclein was not modified by activated tTG in situ. These data
      suggest that tTG is unlikely to be a contributing factor to the formation of
      aggregates of alpha-synuclein in a stable cell model.

PMID- 15460448
TI  - Suppression of CYP1A1 expression by naringenin in murine Hepa-1c1c7 cells.
AB  - Naringenin, dietary flavonoid, is antioxidant constituents of many citrus fruits.
      In the present study, we investigated the effect of naringenin on 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-inducible CYP1A1 gene expression in mouse
      hepatoma Hepa-1c1c7 cells. Naringenin alone did not affect CYP1A1-specific 7
      ethoxyresorufin O-deethylase (EROD) activity. In contrast, the TCDD-inducible
      EROD activities were markedly reduced upon concomitant treatment with TCDD and
      naringenin in a dose dependent manner. TCDD-induced CYP1A1 mRNA level was also
      markedly suppressed by naringenin. A transient transfection assay using dioxin
      response element (DRE)-linked luciferase and electrophoretic mobility shift assay
      revealed that naringenin reduced transformation of the aryl hydrocarbons
      receptor(AhR) to a form capable of specifically binding to the DRE sequence in
      the promoter of the CYP1A1 gene. These results suggest the down regulation of the
      CYP1A1 gene expression by either naringenin in Hepa-1c1c7 cells might be
      antagonism of the DRE binding potential of nuclear AhR.

PMID- 15460449
TI  - Alterations of c-Fos mRNA expression in hypothalamic-pituitary-adrenal axis and
      various brain regions induced by intrathecal single and repeated substance P
      administrations in mice.
AB  - The effect of substance P (Sub P) injected intrathecally (i.t.) on c-fos mRNA
      expression in various tissues was examined in the present study. We found that a
      single administration of Sub P (0.5 nM) caused an increase of the c-fos mRNA
      level in the hypothalamic-pituitary-adrenal (HPA) axis, hippocampus, and spinal
      cord. The time-course study showed that c-fos mRNA level was maximal at 10 min
      and began to decrease 30 min after the Sub P injection in all tissues, and the
      Sub P-induced increase of the c-fos mRNA level was returned to the control level
      1 h after the injection. The kinetics of the c-fos mRNA expression in mice that
      were repeatedly injected with Sub P (every 30 min interval up to 4 times) were
      different in the HPA axis, hippocampus, and spinal cord. The increased c-fos mRNA
      level in the hypothalamus and the spinal cord induced by i.t. injected Sub P
      remained at a high level. In the pituitary gland, adrenal gland, and hippocampus,
      the increased level of c-fos mRNA expression gradually returned to the control
      level during the repeated substance P injections up to 4 times. Our results
      suggest that spinally injected Sub P-induced pain stress increases c-fos mRNA
      expression in the spinal cord, hippocampus, and HPA axis. In mice repeatedly
      injected with Sub P, the kinetics of c-fos mRNA appear to be different varied
      from tissue to tissue.

PMID- 15460450
TI  - Oxidative stress in ovariectomy menopause and role of chondroitin sulfate.
AB  - Oxidative stress due to reactive oxygen species (ROS) can cause oxidative damage
      to cells. Cells have a number of defense mechanisms to protect themselves from
      the toxicity of ROS. Mitochondria are especially important in the oxidative
      stress as ROS have been found to be constantly generated as an endogen threat.
      Mitochondrial defense depends mainly on superoxide dismutase (SOD) and
      glutathione peroxidase (GPx), whereas microsomal defense depends on catalase
      (CAT), which is an enzyme abundant in microsomes. SOD removes superoxide anions
      by converting them to H2O2, which can be rapidly converted to water by CAT and
      GPx. Also, GPx converts hydroperoxide (ROOH) into oxidized-glutathione (GSSG).
      Ovariectomized (OVX) rats are used as an oxidative stress model. An ovariectomy
      increased the levels of MDA, one of the end-products in the lipid peroxidative
      process, and decreased levels of the antioxidative enzymes; SOD, CAT and GPx.
      However, Chondroitin sulfate (CS) decreased the levels of MDA, but increased the
      levels of SOD, CAT and GPx in a dose-dependent manner. Moreover, inflammation and
      cirrhosis of liver tissue in CS- treated rats were significantly decreased. These
      results suggest that CS might be a potential candidate as an antioxidative
      reagent.

PMID- 15460451
TI  - Immobilized beta-cyclodextrin as a simple and recyclable method for cholesterol
      removal in milk.
AB  - This study was designed to determine the optimum conditions of three different
      factors (mixing time, mixing temperature, and tube size) in reduction of
      cholesterol in milk using immobilized beta-CD beads. Immobilized beta-CD glass
      beads were prepared at different conditions of silanization and beta-CD
      immobilization reactions. In result, the glass beads (diameter 1 mm) at 20 mM 3
      isocyanatopropyltriethoxysilane and 30 mM beta-CD without base showed the highest
      cholesterol removal rate as 41%. Using above immobilized beta-CD glass beads, the
      cholesterol removal rate was 40.2% with 6 h of mixing time in 7 mm diameter tube
      at 10 degrees C. After cholesterol removal from milk, the glass beads were washed
      for cholesterol dissociation and reused. In recycling study, the cholesterol
      removal rate was 41%, which was mostly same as that using new glass beads. These
      results indicated that cholesterol removal rate was about 40% with beta-CD
      immobilized glass beads, however, the recycling efficiency was almost 100%.

PMID- 15460452
TI  - Preparation of highly water soluble tacrolimus derivatives: poly(ethylene glycol)
      esters as potential prodrugs.
AB  - Tacrolimus (FK506), which is isolated from Streptomyces tsukubaensis, is a new
      potent immunosuppressant. Because of poor solubility in water, the conventional
      intravenous dosage forms of tacrolimus contain surfactants such as cremophor EL
      (BASF Wyandotte Co.) or hydrogenated polyoxy 60 castor oil (HCO-60) which may
      cause adverse effects. This study relates to a polymer-tacrolimus conjugate,
      which can be dissolved in water, formed by chemically binding the sparingly
      soluble drug, tacrolimus, with the water soluble polymer, methoxypoly(ethylene
      glycol) (mPEG). Water soluble tacrolimus-mPEG conjugates have been synthesized
      and shown to be function in vitro as prodrugs. These conjugates are in the form
      of an ester wherein the 24-, 32- or 24,32-positions are esterified. The desired
      24-, 32- or 24,32-esterified compounds were obtained by initially acylating of
      tacrolimus with iodoacetic acid at the 24-, 32-, or 24,32-positions and then
      reacting the resulting acylated tacrolimus with a mPEG in the presence of a base
      such as sodium bicarbonate. These conjugates were converted again into tacrolimus
      by the action of enzymes in human liver homogenate, and the half-lives of the
      conjugates are approximately 10 min in the homogenate, indicating that the
      esterified tacrolimus derivatives may be practically applicable as a prodrug for
      the immunosuppressant.

PMID- 15460453
TI  - [The School of diagnosis in internal medicine: a strong spring decade!].

PMID- 15460454
TI  - [It is always necessary to ask the girl's hand to her father...].

PMID- 15460455
TI  - [A well-dressed woman from Cameroon].

PMID- 15460456
TI  - [The butcher was sad a heart!...].

PMID- 15460457
TI  - [A gamma, from alpha to omega...].

PMID- 15460458
TI  - [OK for the ball!].

PMID- 15460459
TI  - [Sarcomania has its limits!].

PMID- 15460460
TI  - [An unusual anal ulcer...].

PMID- 15460461
TI  - [Rheumatoid carditis: a diagnosis by exclusion].

PMID- 15460462
TI  - [A diagnosis not as mechanical as it seems to be...].

PMID- 15460463
TI  - [A terrible leg pain...].

PMID- 15460464
TI  - [A real scheming!].

PMID- 15460465
TI  - [The gluttony enzyme and the Story of O].

PMID- 15460466
TI  - [To be or not to be, to die or not to die? That is the question].

PMID- 15460467
TI  - [A treatment that messes one's hair up and works on an unhealthy liver...].

PMID- 15460468
TI  - [Opals bring bad luck, it's well known...].

PMID- 15460469
TI  - [Anemia in Parkinson disease].

PMID- 15460470
TI  - [Horseman's headache].

PMID- 15460471
TI  - [A diagnosis paved with good intentions!].

PMID- 15460472
TI  - [And 1... and 2... and 3 exploratory laparotomies...].

PMID- 15460473
TI  - [His name could have been Arthur...].

PMID- 15460474
TI  - [Did you say cytolysis?... How strange!...].

PMID- 15460475
TI  - [Mother-in-law and daughter-in-law, or the double interrogation].

PMID- 15460476
TI  - [The tenant has a headache].

PMID- 15460477
TI  - [Little holes, little holes, and still little holes...].

PMID- 15460478
TI  - [Fecaloma in the country of green gold].

PMID- 15460480
TI  - [A strange pharyngitis!].

PMID- 15460479
TI  - [Loss of visual acuity and hepatosplenic lesions, it wouldn't be a mystery... in
      Istambul!].

PMID- 15460481
TI  - [Do not take lanterns for bladders!].

PMID- 15460482
TI  - [A history... difficult to digest].

PMID- 15460483
TI  - [A good car driver!].

PMID- 15460484
TI  - [Very severe pregnancy hemolysis...].

PMID- 15460485
TI  - [Two French masters with a "Red-Skin" bed-head].

PMID- 15460486
TI  - [Fiat lux!].

PMID- 15460487
TI  - [Household for 2, 3, or... several?].

PMID- 15460488
TI  - [Where is the problem?].

PMID- 15460489
TI  - [An ugly splenic case].

PMID- 15460490
TI  - [The falx.... bed of greatness].

PMID- 15460491
TI  - [Febrile subdural hematoma].

PMID- 15460492
TI  - [One day it is yes, another day it is no].

PMID- 15460493
TI  - [The balls tumble...].

PMID- 15460494
TI  - [From poetry of cicadas to the laborious reality of ants...].

PMID- 15460495
TI  - Human metapneumovirus: a new pathogen in children and adults.
AB  - In 2001, human metapneumovirus (hMPV) was discovered in young children with
      respiratory tract infection of unknown origin. In the two years since its
      discovery the dinical characteristics of this new virus have been darified. In
      children, especially those younger than one year of age, hMPV is responsible for
      5 to 10% of respiratory tract infections requiring hospitalisation; its clinical
      course is somewhat milder, but otherwise indistinguishable from respiratory
      syncytial virus (RSV) infection. Human MPV can also be found in adults, in
      influenza-like illnesses, but also as a cause of pneumonia. Especially in the
      latter cases immunosuppressive conditions may be present.

PMID- 15460496
TI  - Thrombophilia screening: a matter of debate.
AB  - In the last ten years, several risk factors that increase the risk of venous
      thrombosis have been discovered. Venous thrombosis is a multicausal disease in
      which several risk factors, both genetic and acquired, have to occur
      simultaneously to cause thrombosis. This means that most individuals with single
      thrombophilia are asymptomatic. Although testing thrombosis patients and their
      relatives for thrombophilia factors seems important for tailoring the duration of
      (prophylactic) anticoagulant therapy or estimating the risk of recurrence of
      thrombosis, current data do not support screening for thrombophilia. The risk of
      recurrences or the duration of anticoagulant therapy are generally not altered by
      thrombophilia. Future research should focus on identifying clusters of thrombosis
      risk factors to better estimate the individual risk of thromboembolic events.

PMID- 15460497
TI  - Helicobacter pylori and gastro-oesophageal reflux disease: a cross-sectional
      epidemiological study.
AB  - BACKGROUND: H. pylori infection is accompanied by a lower prevalence of reflux
      disease. There is still an ongoing debate as to whether H. pylori actually
      protects against the development of reflux oesophagitis or is merely an
      epiphenomenon. A cross-sectional study was performed to study the relation of H.
      pylori with reflux oesophagitis, hiatus hernia and Barrett's oesophagus. MATERIAL
      AND METHODS: Consecutive patients undergoing upper gastrointestinal endoscopy in
      a period of ten years were studied. Included were patients with active reflux
      oesophagitis and/or hiatus hernia and/or Barrett's oesophagus. As a reference
      group, patients without macroscopic abnormalities were included. H. pylori was
      detected applying routine diagnostic modalities. RESULTS: In the ten years 11,691
      consecutive patients were studied. Reflux oesophagitis was seen in 1535 patients,
      307 patients had Barrett's oesophagus and a hiatus hernia was present in 2116
      patients. The reference group consisted of 5341 patients. H. pylori was
      significantly less often detected in patients with reflux oesophagitis or
      Barrett's oesophagus compared with the reference group, 20 vs 29% (p<0.001). Also
      presence of H. pylori was significantly lower in patients with hiatus hernia 20
      vs 29% (p<0.0001). CONCLUSION: The present study confirms, in a very large group
      of patients studied in one single centre, the findings of earlier papers.
      Patients without H. pylori gastritis suffer more often from reflux disease. There
      is a relation between H. pylori and reflux disease. However, the consequence of
      this relation will not be the same in every patient.

PMID- 15460498
TI  - The influence of pretreatment on cure rates of Helicobacter pylori eradication.
AB  - BACKGROUND: Many patients treated for H. pylori infection have been taking a
      proton pump inhibitor beforehand. There is conflicting evidence whether
      pretreatment influences the efficacy of H. pylori eradication. The aim of this
      study was to investigate the influence of pretreatment on cure rates of H. pylori
      eradication. METHODS: Patients with H. pylori positive peptic ulcer disease or
      functional dyspepsia were treated with two-day quadruple therapy (lansoprazole 30
      mg twice daily, and colloidal bismuth subcitrate 120 mg, tetracycline 250 mg and
      metronidazole 250 mg, all eight times a day). Patients were randomised to receive
      either three-day pretreatment with lansoprazole 30 mg twice daily or no
      pretreatment. H. pylori was diagnosed using CLO, histology and culture. RESULTS:
      Twenty-five (66%) of 38 patients with pretreatment and 32 (84%) of 38 patients
      without pretreatment were cured (p=0.06). After adjustment for diagnosis, smoking
      status and metronidazole resistance the influence of pretreatment became slightly
      less pronounced (OR 0.44, 95% CI 0.1-1.7). Nonsmokers and patients with peptic
      ulcer disease were more likely to achieve H. pylori eradication than smokers and
      patients with functional dyspepsia, respectively (adjusted odds ratios: 4.79 (1.2
      19) and 4.32 (1.0-18)). CONCLUSIONS: This two-day quadruple therapy reached an
      overall cure rate of 75%. Nonsmokers and patients with peptic ulcer disease were
      more likely to achieve H. pylori eradication. Three-day pretreatment with a
      proton pump inhibitor may decrease cure rates of this two-day quadruple therapy.

PMID- 15460499
TI  - An immunocompromised host with bilateral pulmonary infiltrates.

PMID- 15460500
TI  - Cryptosporidiosis leading to an unsuspected diagnosis of AIDS.
AB  - We describe a 68-year-old woman with an episode of diarrhoea, malaise and weight
      loss, caused by infection with Cryptosporidium. The diagnosis was hampered
      because this patient had a low risk of HIV infection, a two-year history of
      Crohn's disease, and a simultaneous candidal infection. An infection with
      Cryptosporidium was demonstrated with electron microscopic examination, and
      subsequent tests revealed positive HIV serology. AIDS was probably contracted
      through her husband.

PMID- 15460501
TI  - Duodenal metastasis: an uncommon cause of occult small intestinal bleeding.
AB  - Duodenal metastases are a very uncommon and peculiar cause of upper
      gastrointestinal bleeding. However, they should be considered in a patient
      presenting with upper gastrointestinal bleeding and a previous history of
      malignancy. The importance of recognising the unusual presentation of duodenal
      metastasis has to be emphasised. We describe two patients with upper
      gastrointestinal bleeding due to duodenal metastases. In the first patient a
      periampullary bleeding due to a metastasis of a renal cell carcinoma was detected
      five years after nephrectomy of the right kidney. In the second patient an occult
      bleeding caused by a duodenal metastasis of a melanoma was diagnosed. The first
      manifestation of this melanoma was eight years earlier.

PMID- 15460502
TI  - Ocular syphilis acquired through oral sex in two HIV-infected patients.
AB  - Two cases of ocular syphilis are described in HIV-infected individuals after
      unprotected oral sex. The primary syphilitic lesion remained unnoticed and lues
      was therefore only diagnosed after visual symptoms developed.

PMID- 15460503
TI  - Postpartum amenorrhoea-galactorrhoea.

PMID- 15460504
TI  - Community-based participatory research: assessing the evidence.

PMID- 15460505
TI  - Curious asymmetries. Part 2.

PMID- 15460506
TI  - Stereoscopic matching and the aperture problem.
AB  - In order to perceive stereoscopic depth, the visual system must define binocular
      disparities. Consider an oblique line seen through an aperture formed by flanking
      occluders. Because the line is perceived behind the aperture, the line must have
      disparity relative to the aperture. What is the assigned disparity of the line in
      this aperture problem? To answer this question five observers adjusted the
      horizontal disparity of a probe until it was perceived at the same depth as the
      disparate line behind the aperture. The results show that, when both the
      horizontal and the vertical disparities of the occluders are well-defined, the
      probe must have the same horizontal disparity as the horizontal separation
      between the line half-images. However, when the horizontal and vertical
      disparities of the occluders are ill-defined, the intersections of the line and
      the occluder borders can determine the matching direction. In the latter case,
      the matching direction varies with the aperture orientation and there is
      considerable variability across observers.

PMID- 15460507
TI  - Judging egocentric distance on the ground: occlusion and surface integration.
AB  - On the basis of the finding that a common and homogeneous ground surface is vital
      for accurate egocentric distance judgments (Sinai et al, 1998 Nature 395 497
      500), we propose a sequential-surface-integration-process (SSIP) hypothesis to
      elucidate how the visual system constructs a representation of the ground-surface
      in the intermediate distance range. According to the SSIP hypothesis, a near
      ground-surface representation is formed from near depth cues, and is utilized as
      an anchor to integrate the more distant surfaces by using texture-gradient
      information as the depth cue. The SSIP hypothesis provides an explanation for the
      finding that egocentric distance judgment is underestimated when a texture
      boundary exists on the ground surface that commonly supports the observer and
      target. We tested the prediction that the fidelity of the visually represented
      ground-surface reference frame depends on how the visual system selects the
      surface information for integration. Specifically, if information is selected
      along a direct route between the observer and target where the ground surface is
      disrupted by an occluding object, the ground surface will be inaccurately
      represented. In experiments 1-3 we used a perceptual task and two different
      visually directed tasks to show that this leads to egocentric distance
      underestimation. Judgment is accurate however, when the observer selects the
      continuous ground information bypassing the occluding object (indirect route), as
      found in experiments 4 and 5 with a visually directed task. Altogether, our
      findings provide support for the SSIP hypothesis and reveal, surprisingly, that
      the phenomenal visual space is not unique but depends on how optic information is
      selected.

PMID- 15460508
TI  - The effect of support ratio on infants' perception of illusory contours.
AB  - We used a preferential looking technique to investigate the effect of support
      ratio (a ratio of the physically specified contours to the total edge length) on
      the perception of Kanizsa illusory contours in infants aged 3-8 months. Previous
      work has shown that for adult observers the illusory-contour strength increases
      proportionally with the support ratio. When the support ratio was relatively high
      (66%), infants preferred illusory contours to non-illusory figures by 3-4 months
      of age (experiment 1). In contrast, only infants 7-8 months old showed this
      preference for illusory contours when the support ratio was reduced to 37%
      (experiment 3). Further, infants showed no preference for an outline version of
      the illusory-contour figure, which produced no illusory contours (experiment 2).
      This result confirms that the infants' preference reflects their perception of
      illusory contours. Our results show that (i) illusory-contour perception emerges
      at around 3-4 months of age, but (ii) that this ability is very limited until
      around 7-8 months of age.

PMID- 15460509
TI  - The tale is in the tail: an alternative hypothesis for psychophysical performance
      variability in dyslexia.
AB  - Dyslexic groups have been reported to display poorer mean performance than groups
      of normal readers on a variety of psychophysical tasks. However, inspection of
      the distribution of individual scores for each group typically reveals that the
      majority of dyslexic observers actually perform within the normal range.
      Differences between group means often reflect the influence of a small number of
      dyslexic individuals who perform very poorly. While such findings are typically
      interpreted as evidence for specific perceptual deficiencies in dyslexia, caution
      in this approach is necessary. In this study we examined how general difficulties
      with task completion might manifest themselves in group psychophysical studies.
      Simulations of the effect of errant or inattentive trials on performance produced
      patterns of variability similar to those seen in dyslexic groups. Additionally,
      predicted relationships between the relative variability in dyslexic and control
      groups, and the magnitude of group differences bore close resemblance to the
      outcomes of a meta-analysis of empirical studies. These results suggest that
      general, nonsensory difficulties may underlie the poor performance of dyslexic
      groups on many psychophysical tasks. Implications and recommendations for future
      research are discussed.

PMID- 15460510
TI  - The AMBEGUJAS phenomenon and colour constancy.
AB  - The AMBEGUJAS phenomenon is a reversible flat figure that is spontaneously
      shifting between two apparent 3-D shapes-'tile' and 'roof'. 2-D perceptions have
      very rarely been reported. Tied to the shifts between the tile and roof shapes
      are remarkable changes of perceived colour. In our example, the tile appears to
      have orange (top half) and blue-green (bottom half) surface colours in white
      light. The roof appears grey but in an orange illumination and with a blue-green
      shadow. This phenomenon appears whether a grey display is presented in two
      coloured illuminations, or a chromatic display with two surface colours (orange
      and blue-green) is presented in white light. In the coloured illuminations the
      tile is an example of non-constancy, since its colours are non-veridical colour
      perceptions. The centre stripe of the display appears to have the same orange and
      blue-green colours as the lateral stripes but in a shadow. This seems like a
      colour constancy in a non-constancy situation. An alternative to the classical
      definition of colour constancy is discussed.

PMID- 15460511
TI  - Creating noisy stimuli.
AB  - A method for creating a variety of pseudo-random 'noisy' stimuli that possess
      several useful statistical and phenomenal features for psychophysical
      experimentation is outlined. These stimuli are derived from a pseudo-periodic
      function known as multidimensional noise. This class of function has the
      desirable property that it is periodic, defined on a fixed domain, is roughly
      symmetric, and is stochastic, yet consistent and repeatable. The stimuli that can
      be created from these functions have a controllable amount of complexity and self
      similarity properties that are further useful when generating naturalistic
      looking objects and surfaces for investigation. The paper addresses the creation
      and manipulation of stimuli with the use of noise, including an overview of this
      particular implementation. Stimuli derived from these procedures have been used
      successfully in several shape and surface perception experiments and are
      presented here for use by others and further discussion as to their utility.

PMID- 15460512
TI  - Visual synaesthesia in the blind.
AB  - Synaesthesia is characterised by idiosyncratic ectopic sensations which commonly
      take the form of coloured visual impressions evoked by touch or hearing. We
      studied six late-blind individuals who have retained synaesthetic colour
      perception. Four of them had been without any form of genuine colour vision for
      more than 10 years. All perceived colours when they heard or thought about
      letters, numbers, and time-related words (days of the week and months of the
      year). One experienced synaesthetic colours for all words. Another saw Braille
      characters as coloured dots when he touched them. The aberrant experiences were
      compelling and reliable: detailed verbal descriptions of the colours were
      remarkably consistent in tests more than 2 months apart. The percepts
      predominantly took the form of coloured patches, localised in body-centred space
      for five of the subjects and in head-centred space for the sixth. This implies
      that the neural activity underlying synaesthesia occurs after the establishment
      of a visual representation independent of eye (or head) position. The
      synaesthetic colour depended only on phonetic cues in one case, but on semantic
      context in others. Although synaesthesia might be due to idiosyncratic, aberrant
      corticocortical connectivity established during early development, it can persist
      for very long periods with little or no natural experience in the referred
      modality and therefore does not depend solely on continuing associative learning.

PMID- 15460513
TI  - Visual neuroscience before the neuron.
AB  - Visual neuroscience is considered to be a contemporary concern, based in large
      part on relating characteristics of neural functioning to visual experience. It
      presupposes a detailed knowledge of neural activity for which the neuron doctrine
      is a fundamental tenet. However, long before either the neuron doctrine had been
      advanced or the nerve cell had been described, attempts were made to estimate the
      dimensions of nerve fibres from measures of visual resolution. In the seventeenth
      century, the microscopes of Hooke and van Leeuwenhoek were unable to resolve
      structures as small as nerves adequately. However, it was not Hooke's microscope
      that led to an estimate of the dimensions of nerve fibres but his experiments on
      the limits of visual resolution. Hooke determined that a separation of one minute
      of arc was the minimum that could normally be seen. Descartes had earlier
      speculated that the retina consisted of the terminations of fibres of the optic
      nerve, and that their size defined the limits of what could be seen. Estimates of
      the diameters of nerve fibres were made on the basis of human visual acuity by
      Porterfield in 1738; he calculated the diameters of nerve fibres in the retina as
      one 7200th part of an inch (0.0035 mm), based on the resolution of one minute of
      arc as the minimum visible. In the same year, Jurin questioned the reliability of
      such estimates because of variations in visual resolution with different stimuli.
      The measurement of visual acuity was refined by Mayer in 1755, with dots,
      gratings, and grids used as stimuli. In the 1830s, Treviranus fused the
      microscopic and acuity approaches to determine the dimensions of nerve fibres.
      His indirect estimates of the dimensions of retinal fibres were close to those
      derived from microscopic observation. However, the suggestion that the retina
      consisted of terminations of nerve fibres influenced his detailed illustrations
      of its microscopic structure. Contrary to the situation that obtained after the
      microscopic structure of the retina had been established, a function of vision
      (acuity) was used to determine the dimensions of the structures (retinal
      elements) that were thought to mediate it.

PMID- 15460514
TI  - Keynote address to Dynamics 2003 delegates.

PMID- 15460515
TI  - High alert: Preventing insulin errors.

PMID- 15460516
TI  - Walking the walk: living evidence-based practice.
AB  - Evidence-based clinical practice is a goal of professional nursing. Linking
      research to the clinical realm appears logical and sounds simplistic, yet
      frequently our preconceived thoughts and ideas of ease of change do not equate
      with the reality of the situation. The research exists, the need is there, but
      "how shall the two meet?" In this article, the authors describe the successful
      implementation of a multidisciplinary evidence-based clinical practice guideline
      in the pediatric intensive care unit (PICU) at Winnipeg Children's Hospital.
      Maintaining artificial airways was a frequent topic of discussion in this PICU.
      The questions surrounding this practice were reviewed using an evidence-based
      practice framework in order to provide a clinical practice guideline that would
      assist in the delivery of care.

PMID- 15460517
TI  - Managing diabetic ketoacidosis: the role of the ICU nurse in an endocrine
      emergency.
AB  - Diabetic ketoacidosis is an endocrine emergency that requires intensive
      management and monitoring. Eight per cent of diabetic-related admissions are for
      the management of diabetic ketoacidosis and, prior to the discovery of insulin,
      all of these patients died (Delaney, Zisman & Kettyle, 2000). In this article,
      the author reviews the pathophysiology of the classic presentation of diabetic
      ketoacidosis: hyperglycemia and ketoacidosis. The management of the acute
      situation is described in order to enable the critical care nurse to provide and
      advocate for best patient care practices.

PMID- 15460518
TI  - Analgesic and sedative pharmacology in the intensive care unit.
AB  - Sedation and analgesia are central elements in the care of critically ill,
      mechanically-ventilated patients. The goal of analgesic therapy is to provide
      relief from pain and physical discomfort which may lead to poor sleep, agitation,
      or a stress response. Opioids, such as morphine, fentanyl, and hydromorphone, are
      considered first-line agents for treating pain. All of these agents are equally
      effective at equipotent doses and the choice of an agent depends on both drug and
      patient characteristics. Sedatives with amnestic properties are desirable to
      prevent or relieve anxiety and agitation. The benzodiazepines and propofol are
      the primary sedative agents used in the intensive care unit (ICU). Agents such as
      clonidine and haloperidol may have a role in the ICU when used concomitantly with
      sedatives and analgesics. An understanding of the pharmacotherapy of sedation and
      analgesia in the ICU will help support appropriate usage of these agents and
      improve patient care.

PMID- 15460519
TI  - Defining the great debate.
AB  - Treatment guidelines offer a credible approach to MCO management of specialty
      pharmaceuticals by basing decisions on the best available scientific evidence.
      Drawbacks to using guidelines include lack of available evidence, bias on the
      part of the expert team, a lack of currency, and difficulties in implementation.
      Treatment guidelines can and often do serve, along with product labeling, as the
      basis for reimbursement and usage rules as specified in MCO medical policies. The
      relationship between provider-oriented guidelines and payment criteria varies by
      payer, with implications for care quality, cost, and access. Increased awareness
      of the advantages and disadvantages of using treatment guidelines to shape
      prescribing policies for specialty pharmaceuticals may lead to worthwhile non
      product-specific discussions within MCOs about sources and methods used in
      medical policy development.

PMID- 15460520
TI  - Specialist discretion for managing specialty pharmaceuticals: the ethics argument
      for discretion.

PMID- 15460521
TI  - Consensus guidelines for specialty pharmaceuticals: a best-practice approach for
      cost-effective management.

PMID- 15460522
TI  - Can modulation of viral fitness represent a target for anti-HIV-1 strategies?
AB  - Prolonged use of anti-retroviral compounds in human immunodeficiency virus type 1
      (HIV-1) infection selects for drug-resistant and often mutidrug-resistant viral
      variants. Drug-resistance mutations may also affect viral fitness. Interestingly,
      recent research has indicated that some of the unfit drug-resistant variants may
      be less pathogenic, suggesting that decreased viral fitness is beneficial for the
      host and may be driven by specific treatments during anti-HIV-1 infection. A
      second potential antiviral strategy starting with profound inteference with viral
      fitness aims at forcing viruses towards lethal mutagenesis (the so-called "error
      catastrophe"). This review summarizes the methods for addressing HIV-1 fitness in
      vitro and ex vivo, the current understanding of clinical implications of reduced
      HIV-1 fitness, and the potential use of anti-HIV-1 strategies aiming at
      modulating viral fitness. Finally, it is emphasized how the peculiar features of
      HIV-1 quasispecies (displaying two different forms of memory, a replicative and a
      non-replicative form) may sharply influence the design of future diagnostic
      methodologies for fitness analysis.

PMID- 15460523
TI  - The seroepidemiology of Hepatitis A virus in Amman, Jordan.
AB  - Hepatitis A virus (HAV) has emerged as an important public health problem in many
      countries of the Middle East region and Jordan is no exception. From January 1991
      to December 2001, a total of 1015 patients were diagnosed at Al-Battikhi Medical
      Laboratories. Samples were collected at seventeen private laboratories
      distributed throughout areas of the Governorate of Amman (capital of Jordan). A
      significant variation (P=0.03) was obtained between number of HAV cases and year.
      Seasonal variation in HAV cases was seen throughout the study period with maximal
      rates in the spring and summer months (P<0.001). The highest incidence rate
      (9.6/100,000 population) was detected in the year 1993 and the lowest incidence
      rate (1.1/100,000 population) was found in the year 2001. There was a significant
      difference (P<0.0001) between number of HAV cases and age group. The highest
      number of cases 166 (16.4%) was reported for age group 5-14 years and the lowest
      number of cases 18 (0.02%). Male to female ratio was 1.25: 1. There was no
      significant sex variation (P=0.28). A significant variation (P=0.006) was
      observed between number of HAV cases and districts. The present results suggested
      a link between the age groups, year, month and occurrence of HAV infection. Male
      to female ratio indicates no significant sex variation.

PMID- 15460524
TI  - Direct rapid diagnosis of rifampicin-resistant M. tuberculosis infection in
      clinical samples by line probe assay (INNO LiPA Rif-TB).
AB  - M. tuberculosis is one of the leading causes of death worldwide and Multi Drug
      Resistant Tuberculosis (MDR-TB) is associated with a high case-fatality rate.
      Rapid identification of resistant strains is crucial to institute prompt
      appropriate therapy, and prevent the development of further resistance and
      spreading of MDR strains. The INNO-LiPA Rif. TB is a commercial reverse
      hybridisation line probe assay designed for rapid detection of rpoB gene
      mutations in clinical isolates. We applied this test directly to 44 smear
      positive and 45 smear-negative clinical specimens collected from patients
      suspected of active TB. The capability of this technique to correctly identify
      local MDR-TB strains was tested on 50 MDR strains isolated in Italy. Results of
      the test were compared to conventional antibiogram performed on isolated strains.
      The concordance rate of the LiPA test results on clinical specimens with those
      obtained with "in vitro" sensitivity was 100%. These results show that the LiPA
      test can be useful in rapid detection and prompt management of tuberculosis when
      MDR disease is suspected.

PMID- 15460525
TI  - Relationship between dyslipidemia, C-reactive protein and serological evidence of
      Chlamydia pneumoniae in Turkish patients with coronary artery diseases.
AB  - Relationship between dyslipidemia, C-Reactive Protein (CRP) and serological
      evidence of Chlamydia pneumoniae was investigated in a Turkish population with
      coronary artery disease. This prospective, randomized, blinded study was carried
      out in Florence Nightingale Hospital which is affiliated to Kadir Has University,
      Medical Faculty. Thirty-two patients with acute coronary artery diseases (ACAD),
      32 patients with chronic coronary artery diseases (CCAD) and 26 healthy controls
      (HC) were included in the study. We detected serum concentrations of C.
      pneumoniae IgG, IgA and IgM by ELISA method. We measured total cholesterol,
      trigliseride, LDL and HDL- cholesterol levels to determine dyslipidemia which was
      defined as total cholesterol >200 mg/dL, trigliserid > 150 mg/dL, LDL >130 mg/dL,
      HDL <45 mg/dL. CRP levels were also measured. Seropositivity to C. pneumoniae IgG
      was 84.3%, 100% and 65.3%; seropositivity to IgA was 9.3%, 6.2%, and 3.8%; and
      seropositivity to IgM was 12.5%, 15.3%, and 15.4% in patients with ACAD, CCAD and
      HC, respectively. Dyslipidemia was found as 93.7%, 78. 1% and 0% of patients with
      ACAD, CCAD and HC, respectively. CRP level was high in all patients (ACAD, CCAD)
      but not in healthy controls. As a conclusion, we found a significant association
      between seropositivity to C. pneumoniae IgG and dyslipidemia and CRP levels in
      ACAD and CCAD patients (p<0.05). C. pneumoniae IgG antibodies should be evaluated
      together with serum lipids and CRP levels in patients with ACAD and CCAD in
      Turkish population. This may help clinicians in treatment of C. pneumoniae
      infection and decrease the risk of coronary artery diseases.

PMID- 15460526
TI  - Use of simulated blood cultures for antibiotic effect on time to detection of the
      two blood culture systems BacT/ALERT and BACTEC 9240.
AB  - To avoid the influence of pre-analytical steps, this study was performed using
      sterile blood spiked with defined loads of microorganisms as inoculum. Time-to
      Detection (TTD) was evaluated for the most frequently encountered bacteria
      comparing two commercially available blood culture systems, BD BACTEC 9240
      (Becton Dickinson) and BacT/ALERT (Organon Teknika). The effect of the most
      widely used antibiotics on TTD was evaluated on both systems. TTD was measured
      with antibiotics at their trough and at increasing concentrations. The results
      show that the BACTEC PLUS system recovers more pathogens with shorter time to
      detection than the BacT/ALERT FAN system when beta-lactam antibiotics
      (Ampicillin, Cefotaxime) are present at their respective trough concentration
      corresponding to parenteral therapy. The two systems seem to be equally efficient
      when Gentamicin, Ciprofloxacin and Trimethoprim/sulfamethoxazole are used; in the
      case of Vancomycin, BACTEC seems more effective than BacT/ALERT.

PMID- 15460527
TI  - Effect of cefoxitin and clindamycin on selection of derepressed mutants in
      Enterobacter cloacae.
AB  - The characteristics of an antibiotic that favor its ability to select for
      resistant bacteria are not completely understood. Otherwise, by the common use of
      broad-spectrum cephalosporins, resistant strains of several gram-negative
      species, especially Enterobacter cloacae, have been more frequently isolated.
      During our studies on beta-lactam resistance in E. cloacae, we observed that the
      addition of an inhibitor (clindamycin) to a potent inducer (cefoxitin) leads to
      an enhanced selection of resistant mutants. This could explain the emergence of
      beta-lactam resistant strains during antibiotic therapy.

PMID- 15460528
TI  - Detection and characterization of verocytotoxin-producing Escherichia coli (vtec)
      O157 and non-O157 in cattle at slaughter.
AB  - Between September 2001 to June 2002, 145 samples of bovine caecal content were
      collected at slaughter for verocytotoxin-producing Escherichia coli (VTEC)
      serogroups O157 and non-O157 detection. For E. coli O157 the immunomagnetic
      separation technique was performed. The enterohaemolytic phenotype was the target
      for non-O157 VTEC identification. The vero cell assay (VCA) was performed for
      toxic activity detection. The genomic sequence for VT1, VT2 and intimin (vt1,
      vt2, eae genes) were identified by PCR analysis. Eight VTEC O157 and eight non
      O157 VTEC isolates were detected. VTEC O157, eae-positive strains were shed by
      9.7% of feedlot cattle and by 2.5% of dairy cows. Non-O157 VTEC, eae-negative
      isolates were detected in the intestinal content of 12.5% dairy cows and of 2.1%
      feedlot cattle. VTEC-shedding cattle came from 18.1% of the farms included in the
      study. From cattle faeces, VTEC O91:H- (VT2-positive, eae-negative), responsible
      of human diarrhoeal disease in Europe, was recovered. Other VTEC serogroups
      identified in the present study were O74, O109, O110, O116, and O117.

PMID- 15460529
TI  - E-test method for detecting antibiotic synergy against Pseudomonas aeruginosa
      from neutropenic patients: a cost-effective approach.
AB  - The aim of this study was to evaluate the accuracy of E-test for the detection of
      synergy or antagonism of antibiotic combinations against Pseudomonas aeruginosa
      isolates from neutropenic patients. The activity of levofloxacin or grepafloxacin
      combined with ceftriaxone or cefotaxime against 20 P. aeruginosa clinical strains
      was assessed by checkerboard technique in comparison with results performed by E
      test. The combination grepafloxacin + ceftriaxone appeared to be most effective
      (synergy, 55%) by checkerboard technique. The agreement between checkerboard and
      E-test results was 71.2%. Synergy was detected by checkerboard and E-test methods
      in 35 (43.8%) and 23 (31.3%) of 80 possible combinations, respectively.
      Antagonism was detected once (1.2%) by checkerboard method only. No major errors
      were recorded. E-test was preferable to checkerboard method for the total cost
      (reagent cost + cost of technologist time) (8,60 vs 21,80 euros/test,
      respectively). E-test appeared a promising alternative for testing antibiotic
      combinations although further testing should be performed to better refine this
      metodology.

PMID- 15460530
TI  - Stenotrophomonas maltophilia as a nosocomial pathogen.
AB  - The aim of this study was to investigate the molecular epidemiology of
      Stenotrophomonas maltophilia in a university hospital in Turkey. Thirty nine
      clinical isolates were collected from 37 patients and one from an environmental
      source between 1998 and 2001. Susceptibility to 11 antimicrobials was studied.
      The isolates were categorised into six groups: A through F. Trimethoprim
      sulfamethoxazole was the most active agent against the tested isolates. Genotypic
      analysis by pulsed-field gel electrophoresis (PFGE) of clinical isolates
      identified 21 different PFGE patterns. Three most common clusters were composed
      of 11, seven and four strains. Antimicrobial susceptibility identified multi
      resistant phenotype in all S. maltophilia PFGE clones. All the remaining 18
      isolates (45%) revealed unique PFGE patterns. Resistance was not lower in unique
      strains. The clones mainly with two unique macrorestriction profiles strongly
      suggests nosocomial transmission of these strains from either a common source
      and/or between patients.

PMID- 15460531
TI  - Campylobacter fetus bacteremia in an immunocompromised patient: case report and
      review of the literature.
AB  - A 33-year-old woman underwent a liver transplantation and splenectomy in 1985 and
      had followed immunosuppressive therapy until 1995. Afterwards a non-Hodgkin
      lymphoma was diagnosed and chemotherapy was started. In January 2000, because of
      suspect transplantation rejection she was treated with steroid and
      immunosuppressive therapy. Fever occurred after two months and Cytomegalovirus
      (CMV) infection was diagnosed. Ganciclovir was started with clinical remission.
      In November 2000 fever recurred without clinical symptoms. Lymphoma recurrence
      was excluded and CMV was detected by PCR in several biological fluids. Blood
      cultures were positive for a bacterium that was identified as Campylobacter
      fetus. The patient was successfully treated with intravenous ciprofloxacin. For
      persistent CMV viremia therapy with gancyclovir was stopped and foscarnet was
      used (60mg/Kg/tid i.v. for two weeks). Bacteremia due to C. fetus is rare,
      occurring mainly in immunocompromised patients. In our patient the
      immunosuppressive therapy, chemotherapy for lymphoma and CMV infection had made
      the patient susceptible to bacteremia with this infrequently found bacterium. The
      clinical microbiologist should be aware of this infection in immunocompromised
      hosts.

PMID- 15460532
TI  - Use of a duplex-PCR assay to screen for Feline Herpesvirus-1 and Chlamydophila
      spp. in mucosal swabs from cats.
AB  - Fifty-four ocular and forty-six pharyngeal swabs, collected from 54 cats with
      respiratory syndrome, were analyzed by duplex-PCR to evaluate the presence of
      Feline Herpesvirus type 1 and Chlamydophila spp. Both pathogens are in the
      population of cats and as four cats were positive only in ocular swabs and three
      only in pharyngeal ones, it is deduced that a correct diagnostic approach has to
      foresee the dispatch to the laboratory of both swabs. Furthermore, all
      chlamydophila strains analysed by endonuclease restriction were classified as
      Chlamydophila felis.

PMID- 15460533
TI  - Molecular typing of Staphylococcus aureus isolates from an intensive care unit.
AB  - Seventeen S. aureus clinical isolates, collected from an Intensive Care Unit
      (ICU) during a seven-month period were analyzed to investigate their
      antimicrobial susceptibility and clonal diversity. Eleven isolates (65%) were
      found to be resistant to methicillin (MRSA). Pulsed-field gel electrophoresis
      (PFGE) profiles of genomic DNAs, and analysis of the polymorphisms of the
      variable regions of the protein A (spa) and coagulase (coa) genes revealed a
      lower clonal heterogeneity among MRSA than among methicillin-susceptible isolates
      (MSSA). Two of the MRSA clones were repeatedly isolated in different patients,
      within a variable period of time, suggesting the presence in the ward of a
      resident, endemic and multi-drug resistant MRSA population. Our results also
      emphasize the lower discriminatory power of spa and coa typing compared with PFGE
      typing.

PMID- 15460534
TI  - Intrabiliary rupture of a hydatid liver cyst: a case report.
AB  - Intrabiliary rupture of a hydatid liver cyst is a rare occurrence which may
      result in the development of obstructive jaundice and cholangitis. In this report
      we discuss the diagnostic and therapeutic management of a patient in whom the
      parasitic nature of cholangitis was underestimated due to the small size and site
      of the cyst, and to the misleading concomitant presence of cholelithiasis.

PMID- 15460535
TI  - Impact of surface coating on the adherence of slime producing and nonproducing
      Staphylococcus epidermidis.
AB  - The ability of Staphylococcus epidermidis to grow in the form of a biofilm not
      only facilitates its persistence in the host, but also allows it to survive at
      antibiotic concentrations several orders higher than the Minimum Inhibitory
      Concentration (MIC). We evaluated different surface treatments of hardened
      polystyrene in order to develop a model system for growth of S. epidermidis as a
      biofilm. We assayed for biofilm growth of S. epidermidis clinical isolates on
      unmodified polystyrene, on polystyrene modified by chemical abrasion and on
      polystyrene modified by sulfonation, using either Tryptic Soya Broth or Brain
      Heart Infusion as a growth medium. We concluded that sulfonated polystyrene and
      Brain Heart Infusion provided the best growth system for predicting the ability
      of a clinical isolate to form biofilm (Akaike value 23.680). Using this method,
      biofilm formation was detected in 14 (70%) of ica-positive strains and negative
      in 16 (80%) of ica-negative strains.

PMID- 15460536
TI  - Lipoteichoic acid and muramic acid modulate the expression of CD80/CD86 on THP-1
      cells and CD28/CD152 on Jurkat cells.
AB  - The aim of this study is to evaluate the effect of lipoteichoic acid (LTA) and
      muramic acid (MA) on costimulatory molecules CD80/CD86 on THP-1 cells and
      CD28/CD152 on Jurkat cells. The interactions between these molecules strongly
      influence the immune response through the regulation of cytokine release which,
      on its own, is able to regulate the immunological response by a feedback
      mechanism. Our results show that LTA and MA regulate expression of CD86 on
      macrophages while the expression of CD80 remains unmodified. LTA and MA increase
      the expression of CD86 on THP-1 cells, a macrophage cell line. MA increased
      Jurkat T cells CD152 expression.

PMID- 15460537
TI  - Contribution of in vivo and ex vivo studies to understanding the role of antigen
      presenting cells and T cell subsets in immunity to cattle diseases.
AB  - In vivo and ex vivo studies of the immune system in relation to infectious
      disease that are carried out in the natural target species provide data that are
      relevant to understanding the biology of the immune cells and immunity to
      infection. This is particularly the case for diseases that show host specificity.
      Ex vivo studies that exploit the surgical cannulation of lymphatic ducts have
      allowed access to natural dendritic cells. Investigations of these cells have
      revealed the presence of subpopulations that differ in their ability to stimulate
      T cells and differ in the range of cytokines synthesized. These differences would
      be forecast to have major effects on the bias and type of immune response that
      are induced. Studies in vivo of the effect of depleting T-cell populations with
      monoclonal antibodies (mAbs) have shown how different T-cell populations have
      differing critical roles for different infectious diseases, and how they may
      contribute to the immune response and pathology after infection. Here the case is
      made for how studies in cattle have aided our understanding of immunity to
      several infections that can be exploited for the rational design of effective
      vaccination and control strategies.

PMID- 15460538
TI  - Escherichia coli 0157:H7: an update on intestinal colonization and virulence
      mechanisms.
AB  - Cattle are a major reservoir of Escherichia coli 0157:H7, an important zoonotic
      pathogen that causes hemorrhagic colitis and hemolytic uremic syndrome (HUS).
      Colonization of cattle occurs predominantly in the large intestine, and may
      especially target follicle-associated epithelium (FAE) in the terminal rectum.
      Bacterial colonization involves induction of attaching-effacing (A/E) lesions,
      mediated by type III secreted proteins and an outer membrane protein called
      intimin. ToxB, encoded on plasmid pO157, contributes to adherence of E. coli
      O157:H7 through promotion of the production and/or secretion of type III secreted
      proteins. Production of type III secreted proteins and intestinal colonization
      appear to involve quorum-sensing mechanisms. In the human host, E. coli O157:H7
      may have a preference for FAE in the distal small intestine. The H7 flagellum
      induces production of chemokines such as interleukin 8, and neutrophilic
      infiltration of the intestinal mucosa, which in turn may enhance Shiga toxin
      (Stx) uptake across the intestinal epithelium. Both Stx and cytokine responses
      play critical roles in the induction of the vascular lesions that underlie
      hemorrhagic colitis and HUS. In cattle, Stx binds to intestinal crypt cells and
      submucosal lymphocytes but not vascular endothelium. The role played by Stx in
      cattle may be to suppress mucosal immunity, yet enhance other effects that
      promote intestinal colonization.

PMID- 15460539
TI  - Recent pre-harvest supplementation strategies to reduce carriage and shedding of
      zoonotic enteric bacterial pathogens in food animals.
AB  - Food-borne bacterial illnesses strike more than 76 million North Americans each
      year. Many of these illnesses are caused by animal-derived foodstuffs. Slaughter
      and processing plants do an outstanding job in reducing bacterial contamination
      after slaughter and during further processing, yet food-borne illnesses still
      occur at an unacceptable frequency. Thus, it is imperative to widen the window of
      action against pathogenic bacteria. Attacking pathogens on the farm or in the
      feedlot will improve food safety all the way to the consumer's fork. Because of
      the potential improvement in overall food safety that pre-harvest intervention
      strategies can provide, a broad range of preslaughter intervention strategies are
      currently under investigation. Potential interventions include direct anti
      pathogen strategies, competitive enhancement strategies and animal management
      strategies. Included in these strategies are competitive exclusion, probiotics,
      prebiotics, antibiotics, antibacterial proteins, vaccination, bacteriophage,
      diet, and water trough interventions. The parallel and simultaneous application
      of one or more preslaughter strategies has the potential to synergistically
      reduce the incidence of human food-borne illnesses by erecting multiple hurdles,
      thus preventing entry of pathogens into the food chain. This review emphasizes
      work with Escherichia coli O157:H7 to illustrate the various strategies.

PMID- 15460540
TI  - AU-rich elements and the control of gene expression through regulated mRNA
      stability.
AB  - The regulation of gene expression is a fundamental cellular process that is
      controlled at multiple levels. Abnormal regulation of gene expression has been
      directly implicated in the pathogenesis of some diseases of animals and humans
      and may contribute to the disease process in unrecognized ways in many others.
      Furthermore, novel treatment strategies for a number of different diseases may
      hinge upon our ability to exploit mechanisms that normally alter the expression
      of endogenous genes. While the study of gene regulation has traditionally focused
      on transcription as a major regulator of gene expression, it has recently become
      apparent that the post-transcriptional control of gene expression may play an
      equally important role. In particular, rapid, context-specific regulation of the
      stability of mRNA transcripts encoding highly active proteins, such as cytokines,
      growth factors, oncogenes and cell-cycle regulators, appears to play a key role
      in the control of these molecules and the processes they mediate. Many of the
      known regulatory pathways for mRNA stability involve proteins that interact with
      specific AU-rich elements in the 3'-untranslated region of the transcript. This
      review will address some important aspects of the normal regulation of mRNA
      stability and known or potential contributions of RNA stability regulation to
      health and disease.

PMID- 15460541
TI  - Infectious salmon anemia virus: causative agent, pathogenesis and immunity.
AB  - Infectious salmon anemia (ISA) virus (ISAV), an economically important new
      pathogen in marine aquaculture, is classified in the family Orthomyxoviridae,
      genus Isavirus. The main structural properties of this genus include enveloped
      virions 90-140 nm in diameter with surface projections of a combined receptor
      binding hemagglutinin and receptor-destroying enzyme activity demonstrated to be
      an esterase, hence recently designated HE, and a genome composed of eight
      segments of linear, single-stranded, negative sense RNA ranging in length from
      1.0 to 2.4 kb, with a total size of approximately 14.3 kb. The viral genome
      encodes at least ten proteins, of which nine are structural and one is non
      structural. Examination of more than 160 ISAV isolates has led to the
      identification of two hemagglutinin subtypes of ISAV, one North American and one
      European. The immune response against ISAV after infection or vaccination does
      not provide full protection against the infection. The recent discovery of
      antibody-mediated uptake and replication of ISAV in macrophage-like fish cell
      lines suggests that Fc receptor-mediated antibody-dependent enhancement of the
      ISA virus infection might also occur in vivo, as the virus in Atlantic salmon
      (Salmo salar) targets endothelial cells lining blood vessels and macrophage-like
      cells. Cumulative mortalities in Atlantic salmon during natural ISA outbreaks and
      experimental infections range from 0 to 100%. ISAV causes fatal systemic
      infections in marine-farmed Atlantic salmon and asymptomatic infections in feral
      fish. Experimentally induced fatal clinical disease in rainbow trout
      (Oncorhynchus mykiss) has identified a correlate of virulence of ISAV that may
      explain its emergence as a fish pathogen.

PMID- 15460542
TI  - Haemophilus somnus virulence factors and resistance to host immunity.
AB  - Haemophilus somnus ('Histophilus somni) is a Gram-negative bacterium and
      opportunistic pathogen associated with multisystemic diseases of bovines. Some
      strains of H. somnus are relatively avirulent, but are biochemically and
      antigenically similar to the virulent strains. Several virulence factors have
      been identified in H. somnus, of which lipo-oligosaccharide phase variation,
      induction of apoptosis, intraphagocytic survival and immunoglobulin Fc binding
      proteins have been well studied. The sequencing of the genomes of two strains of
      H. somnus has facilitated the identification of genes responsible for distinctive
      attributes within this species and related bacteria. The genetic characterization
      of this bacterium will enhance our understanding of H. somnus virulence factors
      and facilitate the development of new and improved vaccines. This review presents
      an overview of H. somnus virulence factors, their role in resistance to host
      defenses and pathogenesis, and the host immune response to this bacterium.
      Current areas of investigation in the post-genomic era and recent insights into
      new pathogenic mechanisms are also discussed.

PMID- 15460543
TI  - Molecular epidemiology of antimicrobial resistance in veterinary medicine: where
      do we go?
AB  - Molecular epidemiology allows us to trace specific microorganisms and mobile
      genetic elements and to assess their epidemiological and evolutionary
      relationships. Examples of molecular epidemiology investigations in veterinary
      hospitals are discussed. They demonstrate the great similarities with the
      situation in human medicine and the potential usefulness of molecular
      epidemiology in our fight against antimicrobial resistance and nosocomial
      infections in veterinary hospitals. A broad knowledge of the diversity of
      antimicrobial resistance determinants in some major groups of pathogens and
      commensals from animals such as Enterobacteriaceae, Pasteurellaceae, enterococci
      and staphylococci is emerging. However, there are important gaps in this
      knowledge, which are discussed here. Many more molecular epidemiology studies
      will be necessary to understand and follow the evolution of the problem in
      veterinary medicine and agriculture on a global scale. To be able to build useful
      surveillance programs and reliable epidemiological models, and to identify
      critical intervention points, we need to improve our understanding of
      antimicrobial resistance at the animal and farm levels. Studies assessing the
      dynamics of bacterial populations and of resistance determinants at these levels
      are desperately needed. Understanding the relationships between antimicrobial
      resistance, colonization factors, and virulence also represents a major issue for
      which molecular epidemiology investigations will be needed.

PMID- 15460544
TI  - Strategies for airway management.
AB  - Airway management is a critical part of anaesthesia practice. Management includes
      mask ventilation, laryngoscopy, endotracheal intubation and extubation of the
      patient. Difficulty can be encountered at any of these stages, potentially
      resulting in significant complications. Thorough preoperative assessment, as well
      as careful planning and preparation, can reduce the potential for complications.
      The American Association of Anesthesiologists (ASA) developed and recently
      revised guidelines for the management of the difficult airway. These guidelines
      focus on strategies for intubation as well as alternative airway techniques that
      can be used when a patient with a difficult airway is encountered.

PMID- 15460545
TI  - Strategies in the high-risk cardiac patient undergoing non-cardiac surgery.
AB  - The risk of perioperative myocardial infarction or cardiac death in patients
      undergoing non-cardiac surgery may be estimated by clinical risk factor analysis
      and by myocardial stress testing. While stress testing modalities accurately
      delineate reversible myocardial ischaemia, their positive predictive value is
      low, and it is not clear whether their implementation improves outcome when
      compared to risk stratification alone. Similarly, it remains to be shown that
      preoperative coronary revascularization is an effective strategy in reducing
      perioperative risk. Recent reports indicate that surgery undertaken in the first
      weeks after percutaneous coronary interventions may be associated with a
      significantly increased rate of major complications. Administration of beta
      blockers and alpha2-adrenergic agonists to high-risk patients reduces surgical
      morbidity and mortality, and the benefits observed with beta-blockers may extend
      long after the operative period. In high-risk patients undergoing major surgery,
      pulmonary artery catheter-guided haemodynamic optimization has not been
      associated with better outcomes, whereas use of regional anesthetic techniques
      decreases the incidence of postoperative pulmonary, but not cardiac,
      complications.

PMID- 15460546
TI  - Strategies for perioperative arrhythmias.
AB  - Rapid atrial arrhythmias affect close to one million elderly Americans who
      undergo cardiac or non-cardiac operations annually and have been associated with
      prolonged hospital stays. In contrast, bradyarrhythmias or ventricular
      arrhythmias severe enough to require treatment occur in less than 1% of patients
      who undergo all types of surgery, including cardiac. This article focuses on new
      issues leading to the improved understanding of the pathophysiology and
      mechanisms of post-operative atrial arrhythmias. New approaches directed at
      prophylaxis and acute therapy of atrial arrhythmias are discussed, as are
      recommendations to prevent thromboembolic events. Practice and research agenda
      are proposed.

PMID- 15460547
TI  - Strategies in the patient with compromised respiratory function.
AB  - Respiratory diseases are commonly divided into restrictive or obstructive lung
      diseases. For anaesthesiological considerations restrictive lung diseases appear
      as a static condition with minimal short-term development. Overall, restrictive
      lung diseases don't lead to acute exacerbations due to the choice of anaesthetic
      techniques or the choice of anaesthesia-specific agents. Compared to restrictive
      lung diseases, obstructive lung diseases such as asthma or chronic obstructive
      lung diseases have a high prevalence and are one of the four most frequent causes
      of death. Obstructive lung diseases can be significantly influenced by the choice
      of anaesthetic technique and anaesthetic agent. Basically, the severity of the
      chronic obstructive pulmonary disease (COPD) and the degree of bronchial
      hyperreactivity will determine the perioperative anaesthetic risk. This risk has
      to be assessed by a thorough preoperative evaluation and will provide the
      rationale on which to decide the adequate anaesthetic technique. In particular,
      airway instrumentation can cause severe reflex bronchoconstriction. The use of
      regional anaesthesia alone or in combination with general anaesthesia can help to
      avoid airway irritation and even leads to reduced postoperative complications.
      Prophylactic anti-obstructive treatment, volatile anaesthetics, propofol,
      opioids, and an adequate choice of muscle relaxants minimize the anaesthetic risk
      when general anaesthesia is required. If intraoperative bronchospasm occurs,
      despite all precautions, deepening of anaesthesia, repeated administration of
      beta2-adrenergic agents and parasympatholytics, and a single systemic dose of
      corticosteroids are the main treatment options.

PMID- 15460548
TI  - Strategies of neuroprotection for intracranial aneurysms.
AB  - Neuroprotection for patients with intracranial aneurysms encompasses the
      preservation of brain cells endangered by a limited blood and oxygen supply due
      to aneurysm rupture, clipping or coiling, as well as vasospasm. A large variety
      of prophylactic and therapeutic neuroprotective strategies have been proposed,
      but success in human disease is quite limited. Topics of this chapter are the
      pathophysiology and treatment options of aneurysms, as well as promising
      neuroprotective strategies in further developmental stages: both physiologically
      based (hyperoxygenation, hypothermia, avoidance of hyperthermia and
      hyperglycaemia, hypertension, haemodilution and hypervolaemia) and
      pharmacologically based (antifibrinolytic drugs, calcium antagonists,
      anaesthetics, magnesium, erythropoietin and others). New concepts are ischaemic
      preconditioning, growth factors, and gene therapy. Each strategy is rated on
      underlying evidence, and research agendas are mentioned.

PMID- 15460549
TI  - Strategies for managing the diabetic patient.
AB  - Diabetes mellitus is now classified as either 'type 1' (failure of endogenous
      insulin production) or 'type 2' ('insulin resistance') and can be diagnosed if
      fasting blood glucose is >6.1 mmol/l (110mg/dl) on two separate occasions or
      there is unequivocal hyperglycaemia with acute metabolic decompensation or
      obvious symptoms. The prevalence of the disease is rising and may be as great as
      12-14% in western populations aged over 40 years. Diabetes is complicated by
      micro- and macrovascular consequences of chronically elevated blood glucose
      concentrations, and diabetic patients are over-represented in hospital
      populations, particularly among patients requiring surgical interventions. It is
      associated with increased perioperative mortality and morbidity. Evidence is now
      accumulating that intensive glycaemic monitoring and the administration of
      insulin infusions to achieve tight glycaemic control are associated with an
      improvement of both perioperative mortality and morbidity.

PMID- 15460550
TI  - Renal protection strategies in the perioperative period.
AB  - The development of acute renal failure (ARF) in the perioperative period
      continues to be a vexing condition associated with high morbidity and mortality
      rates which have been unchanged for several decades. In this article I briefly
      review recent research categorizing pathogenesis of ARF and mechanisms of
      recovery. Once ARF is established, its maintenance phase is dependent on several
      mechanisms that interact with cellular integrity. The main focus of the article
      is on assessing clinical and experimental interventions to prevent ARF.
      Unfortunately, existing pharmacological and other interventions show a rather
      limited efficacy in preventing ARF.

PMID- 15460551
TI  - Strategies for transfusion therapy.
AB  - Transfusion of allogeneic red blood cells (RBCs), fresh frozen plasma (FFP) and
      platelets is associated with risks, and outcome studies comparing liberal and
      restrictive transfusion regimens are lacking in surgical patients. Therefore,
      guidelines have been established. They recommend first maintaining normovolaemia
      by the use of crystalloids and colloids. RBC transfusions are recommended for
      haemoglobin levels < 6 g/dl and for physiological signs of inadequate oxygenation
      such as haemodynamic instability, oxygen extraction > 50% and myocardial
      ischaemia (new ST-segment depressions > 0.1 mV, new ST-segment elevations > 0.2
      mV or new wall motion abnormalities in transoesophageal echocardiography). FFP
      transfusions are recommended for urgent reversal of anticoagulation, known
      coagulation factor deficiencies, microvascular bleeding in the presence of
      elevated (> 1.5 times normal) prothrombin time (PT) or partial thromboplastin
      time (PTT) and microvascular bleeding after the replacement of more than one
      blood volume when PT or PTT cannot be obtained. Platelet transfusions are
      recommended prior to major operations in patients with platelet counts <
      50,000/microl, intraoperatively with microvascular bleeding at platelet counts <
      50,000/microl and in the range of 50,000-100,0000/microl following
      cardiopulmonary bypass and in patients undergoing surgery where already minimal
      bleeding may cause major damage such as in neurosurgery.

PMID- 15460552
TI  - Strategies for outpatient anaesthesia.
AB  - With the expansion of ambulatory surgery in the Western world over the last 10
      years, it has become increasingly important to identify patients at risk of
      perioperative complications and to use appropriate methods to decrease these
      risks. The confidential enquiry into perioperative deaths was one of the first
      national programmes instituted to identify patients at risk after the operation.
      Although the focus for this initial enquiry was on perioperative mortality,
      recent developments have increasingly focused on identification of perioperative
      morbid events. The first large prospective study on outpatients found a very low
      incidence of death after ambulatory surgery, but with the acceptance of high-risk
      patients for ambulatory surgery in recent years it is likely that perioperative
      morbidity will increase in the future. Therefore, identification of the patient
      at risk is important in order to apply known strategies to decrease these risks.
      We first need to know what tools are available to detect these 'at-risk'
      patients. Unfortunately, many of the tools used are very subjective and lack both
      sensitivity and specificity. In this chapter, an attempt has been made to outline
      the risks related to surgery, anaesthesia, the patient and the procedure, and
      finally the role of the establishment. Later, strategies are discussed which
      could reduce the perioperative general and cardiorespiratory risks in the
      ambulatory surgical patient. Many of these strategies are derived from the
      inpatient since appropriate data in outpatients are lacking. Future studies
      should thus focus on data derived from outpatients and prospective, randomized,
      double-blind studies in a large population of patients in order to first identify
      the patient at risk and subsequently to use drugs and techniques that reduce
      these perioperative risks.

PMID- 15460553
TI  - Strategies for postoperative nausea and vomiting.
AB  - Significant improvement towards a better control of postoperative nausea and
      vomiting have been achieved in recent years. Today, we understand better who is
      likely to vomit or to be nauseous after surgery. Significant amounts of the huge
      literature on anti-emetic interventions have been systematically reviewed,
      critically appraised and quantitatively synthesized. Thus, we know what anti
      emetic interventions work, and how well they work, and we know their adverse
      effect profile. We also know which interventions have no worthwhile efficacy. A
      rational approach to postoperative nausea and vomiting includes three steps:
      identification of patients at risk, keeping the baseline risk low, and
      prophylactic administration of anti-emetics in those patients who are most likely
      to need them. For patients who are identified as high-risk patients, all
      measurements should be simultaneously initiated (multimodal anti-emesis).

PMID- 15460554
TI  - Strategies for postoperative pain management.
AB  - Despite advances in our understanding of the neurobiology of nociception,
      postoperative pain continues to be undertreated. There are many modalities that
      may provide effective postoperative analgesia, including systemic (e.g. opioids,
      non-steroidal anti-inflammatory agents) and regional analgesic options. The
      particular modality or modalities utilized for a particular patient will depend
      on the risk-benefit profile and patient preferences. Ideally, analgesic options
      should be incorporated into a multimodal approach to facilitate patient recovery
      after surgery.

PMID- 15460555
TI  - Strategies for prophylaxis and treatment for aspiration.
AB  - The absolute incidence of aspiration is difficult to define because of its
      relatively low occurrence and difficulty in diagnosis. The gastric volume
      predisposing to aspiration is larger than 30 ml. Fasting times for fluids have
      reduced; however, a large meal may require 9 hours of preoperative fasting.
      Preoperative carbohydrate-enriched beverages may attenuate postoperative
      catabolism. Aspiration occurs most frequently during induction and laryngoscopy.
      Awake fibre-optic intubation may be a suitable alternative in high-risk cases for
      aspiration. The role of cricoid pressure in anaesthesia needs re-evaluation as
      radiological and clinical evidence suggest that it may be ineffective and may
      impede intubation and ventilation. Chemoprophylaxis does not reduce the severity
      of aspiration pneumonitis as gastric bile is unaffected by these agents and
      induces a worse pneumonitis than gastric acid. Patients may be discharged home 2
      hours after aspirating provided they are clinically unaffected and have
      postoperative surveillance.

PMID- 15460556
TI  - The JICA Training Course, Community-Based Cancer Prevention for Asian Pacific
      Countries, 2004 (Epidemiological approach).

PMID- 15460557
TI  - Proceedings of the consensus meeting: Evidence-Based Recommendations on the
      Management of Febrile Neutropenia in Japan. Honolulu, Hawaii, 8-9 March 2003.

PMID- 15460558
TI  - Clopidogrel loading dose pre-PCI: how high?

PMID- 15460559
TI  - The First Amendment and scientific freedom in the era of bioterrorism.
AB  - The events of 9/11 have raised awareness that certain scientific research in the
      public domain may aid terrorists in their quest to develop biological weapons,
      and there is a legitimate cause for concern in rare cases. Proposed executive
      branch responses are consistent in their approach to the problem: restrain the
      offending research by restricting public access to it in some form or another.
      This paper examines some of the history of the United States (U.S.) government's
      restrictions on scientific communication and the protection that the First
      Amendment affords scientists against such restrictions. It focuses in particular
      on biological science, which has in recent years come under increased scrutiny
      due to fears of "bioterrorism." It concludes that science needs to be vigilant
      against government encroachment, but also needs to become the first line of
      defense in preventing dissemination of potentially dangerous research data.
      Should the exercise of prior restraint against biological research become
      necessary, the guidelines developed at the 2002 Monterey workshop provide a
      useful framework for determining what biological research might cause "direct,
      immediate, and irreparable" harm to national security under the New York Times
      Co. v. United States precedent.

PMID- 15460560
TI  - A look behind the scenes: bioterrorism, smallpox, and public health policy.
AB  - The September 11, 2001 terrorist attacks on the World Trade Center and continued
      conflict in Middle Eastern countries has provoked a strong interest in issues of
      national security. On December 13, 2002 the Bush Administration announced its
      smallpox vaccination policy, the first nationwide "proactive" measure to address
      the threat of bioterrorism. The Program has received mixed reactions as a result
      of partisan issues, tensions in public health policy and federal and state
      jurisdiction, conflicting scientific views, and different risk assessments. The
      slow pace of the program, the difficulties surrounding its implementation, and
      the debates regarding its validity serves as a "case study" to demonstrate
      current short-comings in federal and state anti-terrorist and public health
      policies. The focus will be on the states' public health laws and emergency
      preparedness plans through an analysis of the proposed Model State Emergency
      Preparedness Act. Updating current public health laws combined with increased
      funding of scientific research and the foresight to act "proactively" will reach
      far beyond improving national security. These efforts serve the dual purpose of
      deterring future terrorist attacks while greatly improving responses to a number
      of other health emergencies and disasters.

PMID- 15460561
TI  - Australia's bio-regulatory framework: leading the way for stem cell research.
AB  - Biotechnology in Australia has flourished over the past five years. During this
      time the number of companies has doubled to over 370, and over 40 companies are
      now publicly listed. The total market capitalization of the biotechnology
      companies listed on the Australian Stock Exchange (ASX) in 2003 was US$1.5
      billion. Total market capitalization of the health and biotech companies on the
      ASX was US$13 billion. The size of the total Australian pharmaceutical market in
      2003 was US$9 billion. This article highlights the role of Australia in advancing
      stem cell research and its contribution to biotechnology research, development
      and commercialization.

PMID- 15460562
TI  - Applied research ethics with Aboriginal people: a Canadian dilemma.

PMID- 15460563
TI  - The task for ethics review: should research ethics boards address an approach or
      a paradigm?

PMID- 15460564
TI  - Consent from competent minors and the TCPS guidelines.

PMID- 15460565
TI  - Dilemmas for obtaining consent when working with children in high AIDS prevalence
      regions.

PMID- 15460566
TI  - Informed consent: fictional case scenarios in modified "choose-your-own-ending"
      format.

PMID- 15460567
TI  - Consent issues raised by observational research in organisations.

PMID- 15460568
TI  - The fewer the better--we can never stop all animal testing, but there are other
      things we can do.

PMID- 15460569
TI  - The rush to pick a perfect embryo.

PMID- 15460570
TI  - Parents resort to IVF to choose their baby's sex.

PMID- 15460571
TI  - A conflict of interest--when scientists sign articles that appear in the press,
      we need to be told if they are not quite all they seem.

PMID- 15460573
TI  - Is a new era dawning for embryo screening?

PMID- 15460572
TI  - Babies made to order?

PMID- 15460574
TI  - No-brainer--misplaced faith in "mind-reading" scans is a sure route to injustice.

PMID- 15460575
TI  - Reality bites--do participants in reality TV shows really know what they are
      getting into? Cynthia McVey argues that informed consent isn't all it's cracked
      up to be.

PMID- 15460576
TI  - Behind the mask: mind reading.

PMID- 15460577
TI  - Why we do what--wouldn't it be useful if you could predict the choices people
      were going to make? How close we are to a science of decision making.

PMID- 15460578
TI  - They know what you want--if neuromarketers can find the key to our consumer
      desires, will they be able to manipulate what we buy.

PMID- 15460579
TI  - Private thoughts, public property--brain imaging can already see so deep into our
      private lives that we need to think long and hard about who has access to our
      personal secrets.

PMID- 15460580
TI  - Cloners press on despite UK nay.

PMID- 15460581
TI  - In memoriam--marrying art and genetics to provide an eternal memorial would be
      fine, says James Randerson, if only the science had some substance.

PMID- 15460582
TI  - The boldest cut--the risks are considerable, and some say it shouldn't be done.
      But one team of US surgeons is preparing to carry out the world's first face
      transplant.

PMID- 15460583
TI  - Orthopedic devices; effective data of requirement for premarket approval for hip
      joint metal/polymer or ceramic/polymer semiconstrained resurfacing cemented
      prosthesis. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule to require the
      filing of a premarket approval application (PMA) or a notice of completion of a
      product development protocol (PDP) for the hip joint metal/polymer or
      ceramic/polymer semiconstrained resurfacing cemented prosthesis. The agency also
      is summarizing its proposed findings regarding the degree of risk of illness or
      injury designed to be eliminated or reduced by requiring the devices to meet the
      statute's approval requirements and the benefits to the public from the use of
      the devices. This action implements certain statutory requirements.

PMID- 15460584
TI  - The ambiguity of Jewish ethics.

PMID- 15460585
TI  - Legal principles and decision-making.

PMID- 15460586
TI  - National embryo donation center.

PMID- 15460587
TI  - Images in emergency medicine. Adult epiglottitis.

PMID- 15460588
TI  - Risk prediction for patients with syncope.

PMID- 15460589
TI  - Nonoccupational needlestick injuries and postexposure HIV prevention.

PMID- 15460590
TI  - Screening for severe acute respiratory syndrome in the emergency department.

PMID- 15460591
TI  - Coverage disputes and the prudent layperson standard.

PMID- 15460592
TI  - An unusual case of hypoglycemia in a diabetic patient.

PMID- 15460593
TI  - Catheter occlusion from intravenous phenytoin.

PMID- 15460594
TI  - Moral reasoning in medical ethics.

PMID- 15460595
TI  - Theological and moral aspects of cadaverous donation--heart transplantation from
      the point of view of Islam.

PMID- 15460596
TI  - Surrogate motherhood.
AB  - A "surrogate mother" is a woman who, for financial or other reasons, agrees to
      bear a child for another woman who is incapable to conceive herself. In other
      words, she is a "substitute mother" that conceives, gestates and delivers a baby
      on behalf of another woman who is subsequently to be seen as the "real" (social
      and legal) mother of the child. Though the practice of surrogacy has already
      become a big market in western countries, it has also generated countless
      challenges for the law because it adds a third dimension to the meaning of
      motherhood. Like adoption, surrogacy separates the role of rearing mother from
      what the law has called the natural mother, but gestational surrogacy breaks the
      latter down into the roles of genetic mother and birth mother, leaving two women
      with biological connections to the child. Because surrogacy tends to commodify
      and dehumanize people, and because of all its legal, social, and psychological
      complications, it is obviously not wise to accept surrogacy as an alternative way
      of procreation.

PMID- 15460597
TI  - Three lessons on pop biotech: popular culture provides insights into
      biotechnology and society.

PMID- 15460598
TI  - The wild genetic goose chase: Neil Holtzman talks about genetics and medicine
      [interview by Brandon Keim].

PMID- 15460599
TI  - Fear of influence: conflict of interest in biomedical and genetic research.

PMID- 15460600
TI  - Gertie F. Marx, MD (1912-2004).

PMID- 15460601
TI  - PSA doubling time post radiation: the effect of neoadjuvant androgen ablation.
AB  - OBJECTIVE: To determine whether men who relapse after neoadjuvant androgen
      ablation (NAA) and high-dose radiation therapy (RT) have faster PSA doubling
      times(PSAdt) than those who are treated with RT alone. MATERIALS AND METHODS:
      From a prospective database of 1880 patients treated with RT for localized
      prostate cancer, patients were selected for further study if they had a rising
      PSA profile >1 ng/ml, and were treated with either no NAA, or prolonged NAA
      (defined as 3-12 months NAA) with a minimum 5 years follow-up. ThePSAdt was
      calculated from the exponential line of best fit from the first post-nadir value
      >1 ng/ml to the last PSA prior to secondary intervention. Those patients with a
      rising PSA profile at 5 years of follow-up were further examined with linear
      regression to determine factors of possible independent adverse effect. RESULTS:
      There were 251 patients eligible with rising PSA profiles. Patients treated with
      NAA had higher pre-treatment Gleason scores (p<O.001), PSA (p<O.001), and T stage
      (p<0.001). Median duration of NAA was 5.1 months. Rising PSA profiles occurred in
      78% of the RT-only group and 70% of the NAA group. In regression analysis,factors
      predictive of more rapid PSAdt were pre-treatment Gleason score (p<0.001), pre
      treatment PSA(p=0.025), and T stage (p=0.017). The use of NAA(p=0.4) was not
      significant. CONCLUSION: The use of prolonged NAA in men treated with RT does not
      itself cause a more rapid PSAdt when relapse occurs. Faster relapse observed in
      these men is due to intrinsically more aggressive tumors prior to treatment.

PMID- 15460602
TI  - Contract research organizations (CROs) may be the next trend in clinical trials
      liability.
AB  - Pharmaceutical companies, medical device manufacturers and other biotechnology
      firms face increasing financial pressure as research and development expenses
      rapidly rise, mostly because of the need for longer, larger and more complex
      clinical trials. This environment creates valuable outsourcing opportunities for
      contract research organizations in traditional clinical research and an expanding
      variety of other services. But as contract research organizations (CROs) assume
      more responsibilities for conducting clinical trials, they may also be assuming
      liability risks for injuries to participants and for financial losses that may
      delay the regulatory approval process for a product. This article provides an
      overview of risk management strategy with an analysis of potential liabilities
      and establishes steps that may help minimize these risks.

PMID- 15460603
TI  - How molecular medicine transforms policy (and everything else).
AB  - Molecular medicine (also known as pharmacogenomics, pharmacogenetics, gene-based
      medicine, personalized medicine), after being heralded prematurely as the next
      revolution in medicine, is in the process now of becoming the first big change in
      healthcare of the 21st century. Because its scientific, clinical, ethical,
      financial, and regulatory implications are so far-reaching, it is important to
      define who and what will be affected in order to put the right societal systems
      and policies in place to cope with the change. Leaders of the personalized
      medicine field will be those organizations that see the wave and prepare to
      adjust their traditional planning, relationships, attitudes and management
      approach.

PMID- 15460604
TI  - Understanding orphan drug regulations: an EU and U.S. comparative analysis.
AB  - Whereas orphan regulations exist in almost all ICH regions, they may correspond
      to significantly different types of reality in terms of principles and regulatory
      requirements. The apparent similarity in regulations may lead to misunderstanding
      and cultural gaps between sponsors and regulatory authorities. Based on the
      European and the US experience, we decipher the main points stumbling blocks that
      US sponsor may strike when applying for an orphan designation in the EU. An
      update of the orphan drugs designations is provided as well as the upcoming
      challenges that orphan regulations will meet with the development of pharmaco
      genomics and personalized medicines.

PMID- 15460605
TI  - Justice and medical fees.

PMID- 15460606
TI  - Cloning vs. parenting.

PMID- 15460607
TI  - Artificial nutrition and hydration: recent changes in understanding obligations.

PMID- 15460608
TI  - Human cloning, theology of the body and the humanity of the embryo.

PMID- 15460609
TI  - Recent experiences with legal restrictions and the incidence of abortion in
      Poland.

PMID- 15460610
TI  - The Catholic theology of genetic manipulation.

PMID- 15460611
TI  - [[DRG coding of drug addiction].

PMID- 15460614
TI  - Genes and geneticization? The social construction of autosomal dominant
      polycystic kidney disease.
AB  - Critics of the new genetics argue that contemporary understandings of health and
      illness are becoming increasingly 'geneticized.' Salient implications of this
      critique are explored here within the context of Autosomal Dominant Polycystic
      Kidney Disease (PKD), a life-threatening genetic disease that causes fluid-filled
      cysts in the kidneys and progressive loss of renal function. Although PKD is very
      common, public awareness of the disease remains low and there is little clinical
      emphasis on hereditary aspects. Drawing upon qualitative interviews with 16
      healthcare providers, 13 patients and 15 family members, this paper examines the
      social construction and clinical management of PKD. In particular, interviewees'
      perceptions of the role of genetics in PKD and views on presymptomatic testing
      are considered. Finding little impetus toward early diagnosis and/or
      presymptomatic identification of mutation carriers, we conclude that careful
      empirical study of PKD (or other neglected hereditary conditions) contributes new
      insights into factors mitigating geneticization.

PMID- 15460615
TI  - 'Wonderment and dread': representations of DNA in ethical disputes about forensic
      DNA databases.
AB  - The national DNA Database of England & Wales is the largest forensic DNA database
      in the world. Since 1995 it has quickly developed to hold the genetic profiles of
      over two million people. This collection of tissue samples, taken without consent
      from a sizeable collection of the population, has engendered a number of ethical
      commentaries on its legitimacy as a proportionate response to crime. This paper
      examines the ways in which the ethical discourses, which surround the uses of the
      National DNA Database, drew upon and deployed a number of distinct
      representations of DNA. It is argued that key ideas about DNA have become central
      to everyday assertions about the benefits and dangers of this forensic
      technology.

PMID- 15460616
TI  - Investigating genetic discrimination in Australia: opportunities and challenges
      in the early stages.
AB  - Genetic discrimination, defined as the differential treatment of individuals or
      their relatives on the basis of actual or presumed genetic differences, is an
      emerging issue of interest in academic, clinical, social and legal contexts.
      While its potential significance has been discussed widely, verified empirical
      data are scarce. Genetic discrimination is a complex phenomenon to describe and
      investigate, as evidenced by the recent Australian Law Reform Commission inquiry
      in Australia. The authors research project, which commenced in 2002, aims to
      document the multiple perspectives and experiences regarding genetic
      discrimination in Australia and inform future policy development and law reform.
      Data are being collected from consumers, employers, insurers and the legal
      system. Attempted verification of alleged accounts of genetic discrimination will
      be a novel feature of the research. This paper overviews the early stages of the
      research, including conceptual challenges and their methodological implications.

PMID- 15460617
TI  - In sport, are good genes just another cheat?

PMID- 15460618
TI  - Falling on deaf ears.

PMID- 15460619
TI  - Inviting sex.

PMID- 15460620
TI  - Listening to the tin man.

PMID- 15460621
TI  - Organ donation from a Catholic perspective: to perpetuate a culture of life.

PMID- 15460622
TI  - First person consent: OPOs across the country are adapting to the change.

PMID- 15460623
TI  - The Judeo-Biblical perspective on organ donation: you shall choose life.

PMID- 15460624
TI  - Visual field effects on motion sickness in cars.
AB  - BACKGROUND: It is commonly assumed that car passengers who suffer from motion
      sickness will benefit from being able to see the road ahead. HYPOTHESIS: It was
      hypothesized that variations in the external view (including restrictions to
      forward view and the provision of an artificial real-time video view) would
      affect the development of sickness during a 30-min suburban car journey. METHOD:
      Motion sickness was investigated in 4 experiments using 15 different conditions,
      with 20 subjects in each condition. The conditions involved artificial
      restrictions to view, restrictions arising from different seating positions, and
      the provision of a video view of the road ahead. Subjects provided ratings of
      motion sickness at 1-min intervals during the 30-min journey. The motion sickness
      susceptibility of subjects was matched between groups of subjects and the car
      motions were measured in three axes to determine whether the motion conditions
      were similar across conditions within each experiment. RESULTS: Absence of a
      visual field (blindfolded) resulted in similar sickness to that with no external
      forward view (with or without a side view). A wide or narrow forward view (with
      or without a side view) reduced sickness. For the conditions of these
      experiments, seating position did not significantly affect sickness. The
      provision of a real-time video view of the road ahead did not reduce motion
      sickness. There was circumstantial evidence that horizontal acceleration at
      frequencies below 0.1 Hz contributed to sickness. CONCLUSIONS: It is concluded
      that sickness in cars is dependent on the visual scene. The minimization of
      sickness by the provision of visual information requires improved understanding
      of those factors that combine to cause and suppress sickness.

PMID- 15460625
TI  - Decompression sickness risk model: development and validation by 150 prospective
      hypobaric exposures.
AB  - INTRODUCTION: High altitude exposure has an inherent risk of altitude
      decompression sickness (DCS). A predictive DCS model was needed to reduce
      operational risk. To be operationally acceptable, such a theoretical model would
      need to be validated in the laboratory using human subjects. METHODS: The Air
      Force Research Laboratory (AFRL) has conducted numerous studies on human subjects
      exposed to simulated altitudes in hypobaric chambers. The database from those
      studies was used to develop a statistical altitude DCS model. In addition, a
      bubble growth model was developed using a finite difference method to solve for
      bubble radius as a function of time. The bubble growth model, integrated with the
      statistical model, constitutes the AFRL DCS Risk Assessment Model. Validation of
      the model was accomplished by comparing computer predictions of DCS risk with
      results from subsequent prospective human subject exposures. There were five
      exposure profiles, not previously found in the database, covering a wide
      parameter of ranges of altitude (18,000-35,000 ft), exposure time (180-360 min),
      prebreathe time (0-90 min), and activity level (rest-strenuous) that were used.
      The subjects were monitored for DCS symptoms and venous gas emboli. RESULTS:
      There were 30 subjects who were exposed to each of the 5 altitude profiles. The
      DCS incidence onset curves predicted by the model were not significantly
      different from the experimental values for all scenarios tested and were
      generally within +/- 5% of the actual values. CONCLUSION: A predictive altitude
      DCS model was successfully developed and validated.

PMID- 15460626
TI  - Hypergravity and dehydration-induced shifts of interstitial fluid in the skin
      monitored by ultrasound.
AB  - INTRODUCTION: Spaceflight is associated with a shift of interstitial fluid toward
      the skin of the head and a fluid loss that can decrease superficial tissue
      thickness (TT). To collect the physiological data needed to develop techniques
      for monitoring the hydration status of astronauts during spaceflight, we
      investigated the changes in TT induced by a 12-h nil-by-mouth period and a 30-min
      period of +2 Gz hypergravity measured at forehead and tibia. METHODS: There were
      16 male volunteers who were twice subjected to 30 min of +2 Gz acceleration in a
      human centrifuge, once following an oral fluid load of 250 ml x h(-1) (procedure
      A), and once following a nil-by-mouth period of 12 h (procedure B). The TT at the
      forehead (TT-f) and tibia (TT-t) was measured before (t0), after 10 min (t10),
      and after 30 min (t30) of hypergravity using a miniature 10 MHz A-mode ultrasound
      device. The bodyweight, hematocrit (HCT), and plasma viscosity (PVS) were
      measured at tO and t0. RESULTS: The nil-by-mouth period induced a significant
      weight loss and increase in HCT and PVS. A significant increase was noted in TT
      t, but not in TT-f (p < 0.05). Following both procedures, exposure to
      hypergravity produced declines in TT-f at t10 and t30 compared with baseline (p <
      0.05), whereas TT-t was not influenced. CONCLUSIONS: Changes in interstitial
      fluid load of superficial tissues can be tracked by A-mode ultrasonography. Fluid
      loss-induced changes are best detected at the tibia, hypergravity-induced changes
      at the forehead.

PMID- 15460627
TI  - Hearing and performance during a 70-h exposure to noise simulating the space
      station environment.
AB  - INTRODUCTION: Elevated hearing thresholds have been documented in some astronauts
      after long-term spaceflights although noise levels were lower than those normally
      associated with noise-induced hearing loss in ground-based operations. The
      present study was conducted to determine whether prolonged exposure (70 h) to
      levels (72 dBA) recorded on the International Space Station (ISS) service module
      would impact diverse measures of auditory function, as well as cognition and
      memory, motivation, and cardiovascular function. METHOD: Five mixed gender
      subgroups of five normal-hearing subjects, aged 20-50 yr, were sequestered for 70
      h in an environment that modeled conditions on the ISS. They were assigned to one
      of three background conditions: quiet (n = 5), continuous noise from the ISS
      service module (n = 10), or continuous noise during the day only (n = 10).
      Subjects were tested repeatedly within and across days as individuals or pair
      mates. RESULTS: There were no negative effects of the noise on any of the outcome
      measures. Introduction of a delay or noise in a communication channel used in the
      assessment of speech communicability significantly affected the time taken for
      joint problem solving by partners. DISCUSSION: The results of this study were not
      consistent with the observation of hearing loss measured after spaceflights. Nor
      were changes evident in cognition, motivation, or cardiovascular function.
      Factors which might account for the discrepancy are discussed.

PMID- 15460628
TI  - Caffeine restores engagement speed but not shooting precision following 22 h of
      active wakefulness.
AB  - BACKGROUND: Current military missions occasionally require combat readiness of
      soldiers who might be experiencing a sustained period of activity without sleep.
      Strategies to overcome the debilitating effects of sleep deprivation include the
      ingestion of caffeine. Unknown is the efficacy of caffeine use on specific
      elements of target detection and marksmanship following a modest period of
      sustained wakefulness. METHODS: There were 20 subjects (mean +/- SD of 26.7 +/-
      7.2 yr of age, 179 +/- 6 cm in height, and 84.5 +/- 10.8 kg in weight) who
      participated in double-blind caffeine and placebo trials where each trial
      involved a 24-h control period (with sleep) followed by 22 h of mixed mental and
      physical activity with no sleep. At the end of this period, subjects engaged in a
      1-h rifle-shooting task. Subjects ingested 400, 100, and 100 mg of caffeine or
      placebo at 7.5, 3, and 0 h, respectively, prior to shooting. Measures of shooting
      performance included target engagement time (between target appearance and
      firing), friend-foe discrimination, accuracy, and precision. RESULTS: Most
      measures of performance were degraded in the placebo sleep-deprived condition,
      but only the target engagement time and the number of shots fired were restored
      by caffeine ingestion. CONCLUSIONS: These findings concur with other research
      involving different periods of sleep deprivation, and indicate that the cognitive
      component of the shooting task (i.e., target detection) can benefit from caffeine
      whereas the psychomotor component (marksmanship) does not. It appears that once
      the target is detected, the subject is sufficiently aroused to engage the target
      regardless of the subject's level of alertness prior to detection.

PMID- 15460629
TI  - Modafinil's effects on simulator performance and mood in pilots during 37 h
      without sleep.
AB  - INTRODUCTION: Modafinil is a relatively new alertness-enhancing compound of
      interest to the military aviation community. Although modafinil has been well
      tested in clinical settings, additional studies are required to establish its
      safety and efficacy for use in pilots. OBJECTIVE: The purpose of this study was
      to determine whether modafinil (100 mg after 17, 22, and 27 h without sleep)
      would attenuate the effects of fatigue on fighter-pilot mood and performance
      during 37 h of continuous wakefulness. METHODS: A quasi-experimental, single
      blind, counterbalanced design tested the effects of modafinil in 10 Air Force F
      117 pilots. RESULTS: Modafinil attenuated flight performance decrements on six of
      eight simulator maneuvers. Overall, modafinil maintained flight accuracy within
      approximately 15-30% of baseline levels, whereas performance under the no
      treatment/placebo condition declined by as much as 60-100%. Modafinil decreased
      self-ratings of depression and anger, while improving ratings of vigor,
      alertness, and confidence. Benefits were most noticeable after 24 to 32 h of
      continuous wakefulness. One potential drawback of modafinil was that, at least at
      the 100-mg dose level, the drug's effects were not subjectively salient. Since
      this may lead personnel to escalate the dose without flight surgeon approval,
      personnel should be cautioned regarding this particular drug characteristic.
      CONCLUSION: Although modafinil did not sustain performance at predeprivation
      levels, the present study suggests that modafinil should be considered for the
      military's armament of short-term fatigue countermeasures. Future research will
      evaluate whether 200-mg doses are more beneficial than the 100-mg doses used
      here.

PMID- 15460630
TI  - Changing demographics and vision restrictions in civilian pilots and their
      clinical implications.
AB  - BACKGROUND: The Federal Aviation Administration guides policy decisions through
      the study of medical pathologies and visual disorders common to aviators. The
      purpose of this study is to examine demographic statistics present in the civil
      airman population, including vision restrictions, and their relevance to the
      clinical care of aviators. METHODS: Medical certification data were extracted
      from FAA publications and databases for all civil airmen who were active on
      December 31st of each year from 1976 to 2001. Frequency and medical restriction
      data were delineated into 5-yr increments and analyzed to identify population
      trends for the 25-yr study period. RESULTS: Although the total number of pilots
      has decreased over the study period (-17%), the population of male and female
      airmen holding first-class medical certificates has grown by 119% and 1,241%,
      respectively. The percentage of pilots > or = 40 yr of age has increased by 17%,
      and the average age rose from 36.8 to 42.3 yr. Additionally, the increase in near
      vision restrictions (13%) was more than double that of distant vision
      restrictions (6%) during the study period. As of 2001, 92% of all medical
      restrictions were vision related. CONCLUSION: The results of this study indicate
      that the increasing number of first-class certificate holders, gender-specific
      vision problems for female pilots, and the age-related changes in refractive
      error may present new challenges for eye-care practitioners tasked with advising
      aviators concerning the proper choice of refractive correction.

PMID- 15460631
TI  - Medical disqualification of 275 commercial pilots: changing patterns over 20
      years.
AB  - INTRODUCTION: The medical requirements for commercial pilots are issued by the
      ICAO and the European aviation safety organization JAA. In Norway, the
      Aeromedical Section of the Civil Aviation Authority assesses whether pilots are
      medically fit to fly. This study presents the reasons for medical
      disqualification among the Norwegian commercial pilot population during a 20-yr
      period. METHODS: Files on all disqualified commercial pilots were reviewed and
      subdivided into age groups and diagnostic categories. Different disqualification
      rates were calculated. RESULTS: From the study population of 48,229 pilot-years,
      275 pilots were permanently grounded, which gives a 20-yr average
      disqualification rate of 5.7 per 1,000 pilot-years. DISCUSSION AND CONCLUSIONS:
      For cardiovascular diseases the disqualification rate was lower after 1997 than
      before, which is explained by improved treatment and more lenient requirements.
      In the diagnostic categories, neurology, musculoskeletal, and psychiatric
      diseases, the disqualification rate increased after 1997. This fact is probably
      not attributed to more stringent health requirements, but possibly to the
      attitudes of the pilots, who have become more critical with respect to their
      subjective perception of their working environment and psychosocial factors.

PMID- 15460632
TI  - Perceived body orientation in microgravity: effects of prior experience and
      pressure under the feet.
AB  - Human activities often involve sensing body orientation using cues from gravity.
      Astronauts in microgravity are deprived of those cues and may have difficulty
      with certain tasks. We theorized that experience in microgravity combined with
      mechanically induced pressure under the feet (foot pressure) would improve the
      accuracy of a subject's perception of the body's z-axis as indicated by pointing
      to the subjective horizon (SH). METHOD: Experiments were conducted during
      parabolic flights using five experienced subjects and five novices. Subjects were
      required to raise their arm to point to their SH with eyes closed. Measurements
      were made on Earth and in microgravity, with or without foot pressure. Both
      pointing accuracy and the kinetics of the movement were analyzed. RESULTS:
      Performance by experts was stable under all conditions. However, novices in
      microgravity pointed to a significantly lower SH (16.5 degrees below the 1-G SH)
      and slowed their movements (mean angular velocity of movement: 16.8 degrees x s(
      1) less than in 1 G). Foot pressure improved the performance of the novices so
      that it was closer to that observed at 1 G (8.9 degrees below the 1-G SH).
      DISCUSSION: These results suggest that pressure cues under the feet activated the
      internal model of gravity in the novices, and thus improved the accuracy of their
      perception of their z-axis. Subjects with prior experience in microgravity
      correctly perceived their z-axis without the supplementary input.

PMID- 15460633
TI  - Asymmetry in cerebral blood flow velocity with processing of facial images during
      head-down rest.
AB  - INTRODUCTION: Ability to interpret facial expression is crucial for non-verbal
      communication among humans, and could be affected by changes in cerebral
      circulation during exposure to microgravity or its simulation. METHODS: There
      were 16 subjects (8 men and 8 women) who were exposed to 24 h of -6 degrees head
      down rest (HDR). Transcranial Doppler ultrasonography was used to monitor mean
      blood flow velocity (MBFV) in the middle cerebral arteries bilaterally during
      processing of facial images before, at 6 and 24 h of HDR, and after HDR (Pre-, 6H
      , 24H-, and Post-HDR, respectively). The laterality index was assessed as side-to
      side differences in MBFV relative to Pre-HDR for each condition. RESULTS: For Pre
      HDR, both objects and faces were right lateralized in men (p < 0.001) and showed
      a left lateralization tendency in women (p > 0.05). At 6H-HDR, both object and
      faces were left lateralized in men (p < 0.05), but right lateralized in women (p
      < 0.001). At 24H-HDR, both men and women were left lateralized (p < 0.05). For
      Post-HDR, both remained left lateralized for all tasks (p < 0.05). DISCUSSION:
      HDR alters cerebral lateralization for object and facial stimuli, with opposing
      tendencies in men and women. The gender differences may reflect peculiarities in
      processing strategy for object and faces between men and women. Men use a right
      hemisphere processing strategy for faces and women a left hemisphere strategy.
      The superiority of processing of faces by women compared with men has been
      attributed to left hemisphere based strategy. HDR alters lateralization patterns
      and may thus alter processing strategies for faces.

PMID- 15460634
TI  - Self-reported flight hours vs. company records for epidemiologic studies of
      flight attendants.
AB  - INTRODUCTION: Although there is increased interest in health effects studies of
      aircrew members, the differences between self-reported work history and company
      records, including effects on exposure assessment, are poorly characterized.
      METHODS: We collected both self-reported work history and company records as part
      of a National Institute for Occupational Safety and Health biomonitoring study of
      reproductive hormones in 45 female flight attendants. These two sources of work
      history information were compared to identify differences which might impact the
      assessment of work exposures. RESULTS: There appeared to be consistent
      overreporting of self-reported block time and number of flight segments compared
      with company record-based estimates. Overreporting in turn inflated the
      assessment of two important exposures: cosmic ionizing radiation estimated dose
      and time zones crossed. Factors including domicile, block hours per year of work,
      and length of employment affected the amount and direction of overreporting.
      Comparison to compensated credit hours, including nonflight hours, did not fully
      account for the overreporting. DISCUSSION: Self-report of block time may or may
      not include compensated nonflight hours, resulting in differences when compared
      to company records. Exposure bias is likely to result if the complexities of self
      report are not considered when writing questionnaires. Aircrew members should be
      asked for additional occupational information, and a comparison of self-report
      block time to a sample of company records should be considered prior to exposure
      assessment and epidemiologic analysis.

PMID- 15460635
TI  - Leukocyte counts and neutrophil activity during 4 h of hypocapnic hypoxia
      equivalent to 4000 m.
AB  - INTRODUCTION: Symptoms and signs of infectious disease are increased in subjects
      at altitude. Most infections at altitude are diagnosed clinically and do not have
      objective data to support the diagnosis. Since in vivo innate immune responses to
      hypoxia have not been thoroughly characterized, we investigated the effect of
      acute systemic hypocapnic hypoxia on leukocyte trafficking and neutrophil
      activity in healthy humans at rest. METHODS: Sixteen male subjects [mean +/- SD
      age 28.3 +/- 6.5 yrs, body mass 80.9 +/- 15.9 kg, Vo2peak 4.10 +/- 0.76 L x min(
      1)] breathed a hypoxic gas mixture (F(IO)2 = 12.2%, equivalent to 4000 m; H) or
      normoxic room air (F(IO)2 = 20.9%; N) for 240 min, via a mouthpiece, followed by
      60 min of normal breathing. RESULTS: H induced a differential response in
      peripheral venous blood neutrophils (p < 0.05), lymphocytes (p < 0.01), and
      eosinophils (p < 0.01; 60-240 min), resulting in a relative lymphopenia (H 1.88
      +/- 0.48 and N 2.14 +/- 0.45 x 10(9) L(-1)) and neutrophilia (H 5.2 +/- 1.8 and N
      3.9 +/- 1.1 x 10(9) L(-1)) by 240 and 300 min, respectively. Unstimulated
      leukocyte oxidative activity, as determined by luminol enhanced
      chemiluminescence; plasma elastase, a marker of in vivo neutrophil degranulation;
      and sP-selectin, a marker of endothelial cell activation, did not change
      throughout. DISCUSSION: Differences in immune cell numbers showed a marked
      similarity to changes previously reported in response to intense short- and long
      duration exercise and were attributed to the physiological responses induced by
      acute hypoxia that are known to mediate immune cell trafficking. These findings
      could be relevant to the etiology of conditions where hypoxia and immune cells
      are implicated.

PMID- 15460637
TI  - This month in aerospace medicine history. September 2004.

PMID- 15460638
TI  - Getting to grips with an epidemic.

PMID- 15460644
TI  - Measuring the competence of agency nurses.

PMID- 15460645
TI  - Agency nurse reconsiders her future. Interview by Anne Manchester.

PMID- 15460646
TI  - Kiwi wins top Australian nursing award. Interview by Teresa O'Connor.

PMID- 15460647
TI  - Understanding residuals in Guillain-Barre syndrome.

PMID- 15460648
TI  - Immunisation programme puts stress on nurses.

PMID- 15460649
TI  - Back to basics in union organising.

PMID- 15460650
TI  - Does obstetric experience count for naught?

PMID- 15460651
TI  - Interactive image processing as learning by doing component of a WBT application.
AB  - Web Based Training (WBT) is of increasing importance [1][2]. In [5] the main
      author has presented and discussed an overall approach to WBT for medical image
      processing. In the present contribution the interactive part of the approach is
      discussed in detail and its prototypical realisation in the framework of a client
      server teaching application is presented.

PMID- 15460652
TI  - Quantitative indicators of sonographic image of thyroid gland and their relation
      to antithyroid antibodies in Hashimoto's lymphocytic thyroiditis.
AB  - Sonography is a widely used non-invasive diagnostic tool and its main advantage
      is low cost in comparison with other diagnostic methods such as immunological
      analyses. In this work it is presented the relation between a sonographic image
      of thyroid gland and an immunological status of the patients with Hashimoto's
      lymphocytic thyroiditis (chronic inflammation of the thyroid gland). The results,
      evaluated on a set of 740 B-mode sonographic images from 37 subjects, show that
      raw values of individual image pixels in sonogram of thyroid gland with presence
      and without presence of anti-thyroid antibodies are significantly different
      (means 31.87 and 44.56; standard deviations 8.6 and 11.82; t = 3.4; p = 0.0017)
      and that they can be used for the prediction of presence of anti-thyreoglobulin
      and anti-thyreoperoxidasis antibodies. This result suggests the possibility to
      use this method in clinical diagnostic process for reducing the costs. Also the
      correlation between the image features and the level of antibodies was examined.
      The highest correlation was found for inverse difference moment and the level of
      anti-thyreoperoxidasis (coefficient of determination 0.43).

PMID- 15460653
TI  - A general algorithm for magnetic resonance imaging simulation: a versatile tool
      to collect information about imaging artefacts and new acquisition techniques.
AB  - An innovative algorithm for Magnetic Resonance Imaging (MRI) capable of
      demonstrating the source of various artefacts and driving the hardware and
      software acquisition process is presented. The algorithm is based on the
      application of the Bloch equations to the magnetization vector of each point of
      the simulated object, as requested by the instructions of the MRI pulse sequence.
      The collected raw data are then used to reconstruct the image of the object. The
      general structure of the algorithm makes it possible to simulate a great range of
      imaging situations in order to explain the nature of unwanted artefacts and to
      study new acquisition techniques. The way the algorithm structures the sequence
      has also allowed the easy implementation of MRI data acquisition on a commercial
      general-purpose DSP-based data acquisition board, thus facilitating the
      comparison between simulated and experimental results.

PMID- 15460654
TI  - Using a model of the colour content in retinal fundus images to screen for sight
      threatening diabetic retinopathy.
AB  - The aim of the study was to assess the potential use of a model of the colour
      content in retinal fundus images to screen for sight threatening retinopathy in
      diabetes. Diabetic retinopathy is the most frequent cause of blindness in the
      population of working age in industrialised countries, but efficient therapies do
      exist, and accurate and early diagnosis, and correct treatment can prevent
      blindness in more than 50% of all cases. However, up to 50% of cases of type 2
      diabetes, which comprises 85-90% of all patients, are undiagnosed, with an
      average delay of 10 years between the onset of the condition and diagnosis. In an
      other study we have described how there is a linear relation between age and the
      colour composition of retinal images from non-diabetic subjects. In the present
      study this relation was compared to the colour composition of retinal images from
      diabetes patients. We found that for the patients in the present study there is a
      significant difference in the colour composition between normal subjects and
      diabetic subjects with retinopathy. Although the number of patients in our study
      is too small to allow any conclusion, we suggest that this difference potentially
      may be used as the basis for a simple screening method for sight threatening
      retinopathy in unrecognised diabetes, or potentially may help estimating the risk
      of developing diabetic late complications in newly diagnosed type 2 diabetes.

PMID- 15460655
TI  - Automatic detection of clustered microcalcifications in digital mammograms.
AB  - In this paper we propose a new algorithm for the detection of clustered
      microcalcifications using mathematical morphology and artificial neural networks.
      Considering each mammogram as a topographic representation, each
      microcalcification appears as elevation constituting a regional maxima.
      Morphological filters are applied, in order to remove noise and regional maxima
      that doesn't correspond to calcifications. Each suspicious object is marked using
      a binary image and finally a feed forward neural network classifies every object
      achieving a rate of 90% true positive detections with 0.11 false positives per
      image.

PMID- 15460656
TI  - A new kernel method for microcalcification detection: Spin Glass-Markov Random
      Fields.
AB  - Mammography associated with clinical breast examination is the only effective
      method for mass breast screening. Microcalcifications are one of the primary
      signs for early detection of breast cancer. In this paper we propose a new kernel
      method for classification of difficult-to-diagnose regions in mammographic
      images. It consists of a novel class of Markov Random Fields, using techniques
      developed within the context of statistical mechanics. This method is used for
      the classification of positive Region of Interest (ROI's) containing clustered
      microcalcifications and negative ROI's containing normal tissue. The obtained
      results show that the proposed approach can be successfully employed for
      detection of microcalcifications

PMID- 15460657
TI  - Information on heart repolarization changes obtained from body surface ECG
      potentials.
AB  - Possibility to obtain information about local changes of heart repolarization
      from body surface potentials was studied on a model. Activation-recovery
      intervals (ARI) in surface ECG leads were tested as indicators of changed
      repolarization in the underlying myocardium. ECG signals corresponding to
      activation of myocardium with normal and changed action potential duration were
      simulated on the surface of a realistic inhomogeneous torso. ARI intervals were
      derived from all ECG signals and displayed as surface ARI maps. Results suggest
      that shortening and prolongation of action potentials in anterior myocardial
      regions can be visible in corresponding areas on surface ARI maps while only
      prolongation in postero-lateral regions can be observed. Reproducibility of ARI
      maps was checked on real measurements using 63 and 192 surface ECG leads.
      Obtained ARI maps exhibited acceptable reproducibility with correlation of 0.73
      to 0.87. Based on the model and experimental results it is hoped that ARI maps
      can give some insight into the myocardium repolarization and help to recognize
      tissue with changed properties, primarily in heart regions underlying the
      anterior chest.

PMID- 15460658
TI  - Cardio 7--portable system for high resolution ECG mapping.
AB  - One of the main difficulties in using body surface potential mapping (BSPM)
      techniques is the need of complicated multi-channel measuring system. In this
      paper practical portable ECG mapping system is introduced. The system consists of
      a notebook computer and a data acquisition system box connected to the computer
      by fast IEEE 1284 parallel interface working in ECP mode. Concept of the device
      enables to extend the basic 134-channel high-resolution multi-channel ECG
      amplifying unit up to 256 channels. Application software includes measurement and
      real time monitoring of ECG signals, computation and display of several types of
      body surface potential maps. System can be connected to hospital information
      networks and supply them with measured ECG data for advanced processing or
      central archiving.

PMID- 15460659
TI  - Bioinformatical results based on statistical methods for endectocide products
      against fly-larvae.
AB  - The larvicide effects of three endecticide products were studied against house
      fly larvae. Repeated-measure design was used for the analysis of variance. The
      observed data followed different distributions. For this reason, instead of the
      repeated measure ANOVA, three fast statistical methods were applied
      simultaneously. First, the test for homogeneity was carried out for registered
      samples by using the Friedman test, and the Wilcoxon-Wilcox test was applied for
      pairwise comparisons. Secondly, an extended median test was applied for the same
      problem of test for homogeneity, and the Nemenyi test was used for pairwise
      comparisons. Thirdly, a 2 x 2 contingency table analysis was carried out,
      exploiting the specific feature of the database and informatical tools. The three
      simultaneous evaluations enabled us to come to sound, affirmative conclusions. In
      the course of veterinary-biological interpretation we demonstrated the
      statistically reliable temporal efficiency of the three products. We also
      presented the relative efficiency and recognizable features of the products. We
      highlighted the significantly prompt and long release larvicide effects of the
      drugs. We discussed and compared the information content of the applied
      statistical methods.

PMID- 15460660
TI  - RESIS3D--online information about spatial and temporal spreading of resistant
      pathogens.
AB  - Considering resistances of supposed or identified pathogens is of vital
      importance in antibiotics therapy. Additionally local details play a very
      important role. So the resistance situation can be different on two wards of the
      same facility. Furthermore it is possible that there is spatial extension of
      resistances across the wards that the physicians suppose a future resistance
      development in a specific unit. The idea of RESIS3D is to visualize spatial and
      temporal development of resistant pathogens and to give the attending physician
      (as well as the laboratory) important information for using antibiotics. RESIS3D
      is an addition to our computer-based therapy adviser called ICONS for calculated
      antibiotics therapy in intensive care medicine.

PMID- 15460661
TI  - BioDAQ--a simple biosignal acquisition system for didactic use.
AB  - A simple non expensive device for biosignal acquisition is presented. It mainly
      meets the requirements for didactic purposes specific in medical informatics
      laboratory classes. The system has two main types of devices: 'student unit'--the
      simplest one, used during lessons on real signals and 'demo unit', which can be
      also used in medical practice or for collecting biological signals. It is able to
      record: optical pulse, sphygmogram, ECG (1-4 leads) EEG or EMG (1-4 channels).
      For didactical purposes it has a large scale of recording options: variable
      sampling rate, gain and filtering. It can also be used in tele-acquisition via
      Internet.

PMID- 15460662
TI  - Multidimensional approach for evaluation of system activity of the brain by EEG.
AB  - The way of investigation some fundamental properties of integrative brain
      activity was worked out. Within the framework of the qEEG system for computer
      diagnostics of EEG NeuroResearcher '2001 (Version 7.5) is created modules for
      investigation of multivariate neurodynamic systems of the brain on the base of
      multidimensional spectral EEG and ESCoG analysis. It is intended for doctors and
      neuroscientists who use mathematical methods (classical correlation and spectral
      analysis and newest methods of multidimensional analysis of neurodynamic systems
      of the brain) for quantitative EEG (qEEG) successfully.

PMID- 15460663
TI  - Modelling the effect of alcohol in Type 1 diabetes.
AB  - We have recently shown, in studies with patients with Type 1 (insulin dependent)
      diabetes, that alcohol intake at 2100 hrs significantly reduced blood glucose
      values after 10-12 hours, compared with control studies with no alcohol. We
      hypothesised that this was due to the following effects of alcohol: 1. Alcohol
      metabolism increases NADH, leading to a reduction in hepatic gluconeogenesis; and
      2. increased glycogen phosphorylase activity depletes hepatic glycogen stores; 3.
      After the alcohol is metabolised, hepatic insulin sensitivity is increased,
      leading to the restoration of glycogen stores and reduction in blood glucose
      levels, and 4. consequently, after several hours, glycogen stores and insulin
      sensitivity return to normal. A model describing these changes (DiasNet-Alcohol)
      was implemented into the DiasNet model of human glucose metabolism. Our study
      suggests that the DiasNet-Alcohol model gives a reasonable approximation of the
      effect of alcohol on blood glucose concentration observed in our study and
      supports our hypothesis for the mechanism behind these effects in Type 1
      diabetes.

PMID- 15460664
TI  - Assessment of elderly mobility using a remote multisensor monitoring system.
AB  - This study was designed to estimate the changes of different activities (going to
      bed, getting up, visiting washroom) of elderly as an index of mobility. The
      different values in time and number of the different activities were obtained
      from 16 elderly suffering from Alzheimer's disease in a hospital for short period
      observation adding up 4 months of observation data. Significant agreement in
      different activities (going to bed, getting up, visiting washroom, wandering)
      among the two measurements by multisensor system and by nursing staff notation
      was found. As interesting results, the follow up of a patient is shown for 13
      consecutive nights. These studies show the potential usefulness of assessment of
      night activities as an index of mobility, mirror of motor behaviour. Due to minor
      error, the precise mobility index could not be observed, motor behaviour could
      simply be evaluated.

PMID- 15460665
TI  - Virtual reality stimuli for force platform posturography.
AB  - People relying much on vision in the control of posture are known to have an
      elevated risk of falling. Dependence on visual control is an important parameter
      in the diagnosis of balance disorders. We have previously shown that virtual
      reality methods can be used to produce visual stimuli that affect balance, but
      suitable stimuli need to be found. In this study the effect of six different
      virtual reality stimuli on the balance of 22 healthy test subjects was evaluated
      using force platform posturography. According to the tests two of the stimuli
      have a significant effect on balance.

PMID- 15460666
TI  - Neural networks in recognition of electrical signals recorded from two facial
      muscle sites.
AB  - The present aim was to develop signal analysis methods to recognize muscle action
      potentials recorded with electromyography (EMG) from two facial muscle sites,
      corrugator supercilii (the muscle activated in frowning) and zygomaticus major
      (the muscle activated in smiling). Fourteen subjects produced volitional
      activations on both muscle sites, first, on a single muscle site activation basis
      and finally combinatory activations of both muscle sites. Wavelets and neural
      networks were used to analyse these voluntarily produced bursts of electric
      signals. Our results showed well over 90% recognition rates for all signal types.
      It is possible to utilize these communicative signals, for example, for
      multimodal human-computer interaction.

PMID- 15460667
TI  - Effect of different sources of ventricular repolarization heterogeneity on the
      resultant cardiac vectors. A model study.
AB  - The computer model of ventricular activation was used to study the effects of
      eventual differences in the repolarization pattern between the right and the left
      ventricle, as well as between the apical and the basal parts of the ventricles.
      All changes in model action potential durations (APDs) were performed in the
      range corresponding to the APD variability measured in myocytes. The vectorcar
      diographical spatial T loop was very sensitive on the changes in the right to
      left ventricular gradient of APD, while the similar changes in the apico-basal
      gradient of APD influenced the T loop minimally.

PMID- 15460668
TI  - Extraction of intrinsic timing features of cardiac activation from body surface
      potential maps.
AB  - According to previous modeling studies--propagation of depolarizing wave fronts-
      consists of subintervals, each characterized by a smooth progression of waves
      through the myocardium. At the onset and end of these intervals, abrupt changes
      occur in the 3D pattern of activation waves (e.g. at the time of the collision of
      activation waves with other waves, obstacles or unexcitable myocardium and
      epicardial breakthrough), which manifest themselves in the surface ECG as "jumps"
      (high frequency notches and slurs). The timing of jumps provides diagnostic
      information on bioelectrical tissue properties of the heart. Findings of this
      study validated previous simulation results. Furthermore, essential signal
      processing requirements were formulated for a high-resolution body surface
      potential mapping technology.

PMID- 15460669
TI  - Frequency domain and wavelets applications as methods for ECG signal processing.

PMID- 15460670
TI  - Integration of electronic resources and communication technologies during
      Clinical Reasoning Learning sessions.
AB  - In the last few years, Clinical Reasoning Learning has been used during clinical
      training courses in many universities. The goal of this educational activity is
      to develop problem solving and diagnosis skills in medicine, using previously
      acquired medical knowledge. We propose the integration of educational resources
      and computer systems to help students during the reasoning process, and in order
      to prepare students to look for medical information. We also describe a Computer
      Supported Collaborative Learning Environment that integrates Information and
      Communication Technologies in order to improve the Clinical Reasoning Learning
      Sessions.

PMID- 15460671
TI  - Secure exchange of medical data: requirements and solutions.
AB  - It is now common to access and to exchange data through computer networks. The
      major applications used are Web access and, e-mail. But while there is no
      security concern when accessing classical or anonymous data, the exchange of
      sensitive data (e.g. patient-related information) is subject to legal
      constraints. This paper summarizes the current legal obligations in Switzerland
      and presents state of the art techniques for applying the legal rules. A
      commercial implementation in Switzerland is taken as illustration.

PMID- 15460672
TI  - Time stamp services for trustworthy health communications.
AB  - Trustworthy communication and co-operation requires in general static TTP
      services describing 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
      cooperation such as message identifier, time and location of processes, workflow
      relations and system behaviour. Certified time stamps are important notary's
      functions dealing with the services mentioned above. Within the European RESHEN
      project, the ONCONET regional health network for improving cancer care has been
      moving from system-related to certified time stamps using a local secure time
      stamp server or deploying remote time stamp services provided by an accredited
      CA. After implementing such services at the beginning of 2002, an evaluation of
      the operation modes will be performed during 2002 to derive recommendations for
      optimisation of these important services in national and international health
      networks.

PMID- 15460673
TI  - Cognitive engineering in interface design.
AB  - Today, many medical information systems are not satisfactory to their users. To
      ensure ultimate acceptance of health care information systems asks for systems
      that map on health care workers' tasks and on their cognitive processes in
      performing these tasks. The development of human-oriented computer interfaces
      requires insight in users' information needs and information processing in view
      of the tasks that will be computer-supported. Cognitive engineering aims at
      understanding the fundamental principles behind human activities that are
      relevant in designing a system that supports these activities. The application of
      cognitive engineering methods may therefore contribute to computer systems that
      fit better in health care working practices. We used cognitive engineering
      methods in designing a user interface for a physicians' workstation to support
      them in preparing their patient screening. The information needs and information
      search strategies of 4 physicians were revealed by systematic analyses of verbal
      protocols and video's while they successively worked through 10 paper-based
      patient records in preparing their patient visits. The results of these analyses
      were used as input for the design of a conceptual higher-order model that
      represents both the information needs and information search strategy of these
      physicians. Based on this higher-order conceptual model, we developed paper-mock
      ups and a first prototype of the user interface. The physicians will evaluate
      this prototype in the next phase of the project.

PMID- 15460674
TI  - Readability of patient information on diabetes on the Croatian Web sites.
AB  - Many studies on readability, have shown that patient information is frequently
      written at the reading level too high for the average population to understand.
      The aim of this study was to determine the reading level of patient information
      on diabetes found on the Croatian Web sites and written in Croatian language.
      Patient information on diabetes from 10 Croatian Web sites was tested for
      readability using the SMOG formula. The reading levels of the tested materials
      ranged from 11 to 15, which showed that these materials would not be understood
      by at least 80% of the Croatian adult population.

PMID- 15460675
TI  - Usability assessment study of a web site displaying medical resources on line:
      the CISMeF.
AB  - We present here the usability assessment study of a medical web site dedicated to
      the Cataloguing and Indexing of French speaking Medical web Sites (CISMeF). We
      performed a usability inspection using heuristic evaluation and an empirical
      usability test using a portable lab. The results of the heuristic evaluation show
      usability flaws along guidance, prompting and legibility ergonomic criteria. The
      usability test confirms this result and gives some more hints about the severity
      rating of the problems. From these results, we draw up a set of recommendations
      for the re-engineering of the Human Computer Interface (HCI). We conclude on the
      necessity to integrate usability engineering early enough in the projects
      lifecycle.

PMID- 15460676
TI  - How to find out burning problem of telemedicine?
AB  - Sample of 177 cited papers from Current Contents in year 2001 containing word
      'telemedicine' as a keyword, and/or in title and/or in abstract. Most of papers
      were coming from Journal of Telemedicine & Telecare, International Journal of
      Medical Informatics and Telemedicine Journal & E-Health. Titles and abstracts
      were analysed statistically by using Sphinx Lexica as a tool and lexical
      statistics and lexical analysis as methods. Environment/neighbourhood of words
      potentially reflecting evaluation in telemedicine, enabled to make synthesis:
      evaluation or similar words were mentioned in connections with programs and plans
      of telemedicine application in the whole, with economic issue (minimizing, low
      cost, reducing cost), with ICT evaluation, quality, and scarcely with methodology
      and criteria for evaluation.

PMID- 15460677
TI  - The goals and the perspectives of the common research and development work: the
      Italian-Hungarian bilateral programme.
AB  - According to health politicians at present, the modernisation of the health care
      system is a continuous task of the health policy of governments. The core of this
      modernisation: to have information about the needs of the population and the
      patients, to ensure immaterial and material conditions of health care, to
      organise and direct the process of health care in the interests of the favourable
      results of the outcome of care activities. The fundamental conditions of the
      modernisation to update the health information systems are harmonised on an
      international level. The main goal of the bilateral program is: to develop and
      introduce health informatics telemedicine systems for transmission and
      integration of information systems and health data between structures in Hungary
      and Italy. The program contemplates doing problem-oriented electronic patients
      record structures with a flexible, interactive and high operation-speed knowledge
      basis network for health institutes of both countries.

PMID- 15460678
TI  - Cardiac digital image loops and multimedia reports over the internet using DICOM.
AB  - The authors define an open, scaleable telemedicine architecture to reduce the
      time of reports delivery and consultation; increasing their simplicity via
      introducing common image presentation, storage and telecommunication formats and
      methods for telecardiology. They've developed a software application to implement
      it introducing the most appropriate digital imaging methods and formats using the
      latest available technology.

PMID- 15460679
TI  - A new approach for integration of telemedicine applications into existing
      information systems in healthcare.
AB  - In order to take the full advantage of telemedicine applications, they must
      seamlessly be integrated into healthcare services and their information systems
      (e.g. HIS, POS, RIS). In our approach an HL7/XML-based integration module is used
      1) to exchange documents with information systems; 2) to generate and administer
      documents internally; 3) to present documents. The module fills in pre-defined
      CDA-conforming XML templates with data from HL7 V2 messages. The approach is
      first applied to the teleconsultation service EST in the project ENDOTEL.

PMID- 15460680
TI  - A proposed referral centre based on HL7/XML.
AB  - With the growth of the Inteernet, hospitals have also applied HL7 (Health Level
      Seven) to exchange data between them. The referral system is identified as an
      appropriate application system. The effect of referral is to transfer the patient
      to a suitable hospital in a timely fashion, and to arrange appropriate treatment
      for the patient. Taking advantage of the Internet to exchange referral data can,
      not only accelerate the process of patient referral, but also avoid the
      unnecessary repeat examinations to decrease the waste of medical resources. This
      article builds up a referral-related message according to the HL7 standard, and
      develops a referral centre using the Internet environment, making use of XML
      (eXtensible Markup Language) standard to transform the referral-related data to
      XML format and exchange referral data between platforms. This electronic referral
      mechanism is expected to offer other hospitals experience of improved referral
      practice.

PMID- 15460681
TI  - Generic data modelling and use of XML standard for home telemonitoring of
      chronically ill patients.
AB  - In recent years, internet-based home telemonitoring systems that allow
      transmission of patient data to a central database and offer immediate access to
      the data by the care providers have become available. The adoption of Extensible
      Mark-up Language (XML) as a W3C standard has generated a lot of interest in the
      potential value of this language in health informatics. However the
      telemonitoring systems often work with only one or a few types of medical devices
      and thus are limited in the types of diseases they can monitor. This is because
      different medical devices produce different types of data and the existing
      telemonitoring systems are generally built around a proprietary data schema
      specific for the device used. In this paper, we describe a generic data schema
      for a telemonitoring system that is applicable to different types of medical
      devices and different diseases, and then we present an architecture for the
      exchange of clinical information as data, signals of telemonitoring and clinical
      reports in the XML standard, up-to-date information in each electronic patient
      record and integration in real time with the information collected during the
      telemonitoring activities in the XML schema, between all the structures involved
      in the health care process of the patient.

PMID- 15460682
TI  - The role of XML in medical informatics in Hungary.
AB  - Reforms in healthcare means frequent changes. The author focusing on flexible
      information systems and data structures in healthcare, that gives the chance to
      avoid costly deadlocks, incompatibilities and data chaos--keeping the financial
      and administrative burden of provider and reimbursement information systems at
      low level. He describes data and document exchange among health care providers
      (hospitals, GPs etc.) and the reimbursing insurance institute introducing XML
      (eXtensible Markup Language) technology and it's multimedia extension called SMIL
      (Synchronized Multimedia Integration Language) that well supports large textual
      and multimedia nature of data in healthcare. He presents the most frequent XML
      datasets for reimbursement in Hungary, the validation schemas (Data Type
      Definitions) and procedures, comparing the new and old data file sizes with
      different compressions. The comparison includes different schema file sizes, and
      validation times.

PMID- 15460683
TI  - Indexing of Internet resources in order to improve the provision of problem
      relevant medical information.
AB  - Due to the information overload and the unstructured access to (medical)
      information of the internet, it isn't hardly possible to find problem-relevant
      medical information in an appropriate time (e.g. during a consultation). The web
      offers a mixture of web pages, forums, newsgroups and databases. The search for
      problem-relevant information for a certain knowledge area encounters on two basic
      problems. On the one hand, you have to find in the jungle of the information,
      relevant resources for your individual clinical case (treatment, diagnosis,
      therapeutic option etc..). The second problem consists of being able to judge the
      quality of individual contents of inteernet pages. On the basis of the different
      informational needs of health care professionals and patients a catalog with
      inteernet resources was created to tumor diseases such as lung cancer (small cell
      and non-small cell carcinoma), colorectal cancer and thyroid cancer. Explicit and
      implicit metainformation, if available, such as the title of the document,
      language, date or keywords are stored in the database. The database entries are
      editorially revised, so that further specific metainformation is available for
      the information retrieval. Our pragmatic approach of searching, editing, and
      archiving of internet content is still necessary since most of the web documents
      are based on HTML, which doesn't allow for structuring (medical) information and
      assigning metainformation sufficiently. The use of specific metainformation is
      crucial in order to improve the recall and precision of internet searches. In the
      future, XML and related technologies (RDF) will meet these requirements.

PMID- 15460684
TI  - Web impact factor: a bibliometric criterion applied to medical informatics
      societies' web sites.
AB  - Several methods are available to evaluate and compare medical journals. The most
      popular is the journal Impact Factor, derived from averaging counts of citations
      to articles. Ingwersen adapted this method to assess the attractiveness of Web
      sites, defining the external Web Impact Factor (WIF) to be the number of external
      pages containing a link to a given Web site. This paper applies the WIF to 43
      medical informatics societies' Web sites using advanced search engine queries to
      obtain the necessary link counts. The WIF was compared to the number of
      publications available in the Medline bibliographic database in medical
      informatics in these 43 countries. Between these two metrics, the observed
      Pearson correlation was 0.952 (p < 0.01) and the Spearman rank correlation was
      0.548 (p < 0.01) showing in both cases a positive and strong significant
      correlation. The WIF of medicalm informatics society's Web site is statistically
      related to national productivity and discrepancies can be used to indicate
      countries where there are either weak medical informatics associations, or ones
      that do not make optimal use of the Web.

PMID- 15460685
TI  - Healthcare teams over the Internet: towards a certificate-based approach.
AB  - Healthcare environments are a representative case of collaborative environments
      since individuals (e.g. doctors) in many cases collaborate in order to provide
      care to patients in a more proficient way. At the same time modem healthcare
      institutions are increasingly interested in sharing access of their information
      resources in the networked environment. Healthcare applications over the Internet
      offer an attractive communication infrastructure at worldwide level but with a
      noticeably great factor of risk. Security has therefore become a major concern
      for healthcare applications over the Internet. However, although an adequate
      level of security can be relied upon digital certificates, if an appropriate
      security policy is used, additional security considerations are needed in order
      to deal efficiently with the above team-work concerns. The already known Hybrid
      Access Control security model supports and handles efficiently healthcare teams
      with active security capabilities and is capable to exploit the benefits of
      certificate technology. In this paper we present the way for encoding the
      appropriate authoritative information in various types of certificates, as well
      as the overall operational architecture of the implemented access control system
      for healthcare collaborative environments over the Internet. A pilot
      implementation of the proposed methodology in a major Greek hospital has shown
      the applicability of the proposals and the flexibility of the access control
      provided.

PMID- 15460686
TI  - InfoServerPlus: providing a medical library as application service.
AB  - Clinical decision making necessitates convenient access to high-quality content.
      The advanced requirements for a multipurpose application must be met
      technologically by an appropriate system design in the form of a client-server
      architecture which demonstrates a functional view in differentiating three tiers:
      presentation, application and data supply. The technical realisation has been
      accomplished by an application server which serves thin clients on several
      platforms. Despite considerable expenditures, this solution represents a
      promising way of disseminating information and knowledge via Intra- and Internet.
      The requirements and the accompanying system architecture could be satisfactorily
      implemented.

PMID- 15460687
TI  - Telebaby videostreaming of newborns over Internet.
AB  - New information technologies are used to fill gaps in our need for communication.
      Hospitals are now starting to discover the possibilities of multimedia
      communication for their patients. Telebaby is a project of the University Medical
      Centre Utrecht that allows parents to view their newborn on the intensive care,
      high care or medium care unit at home. Standard Internet technology for
      distributing multimedia allows parents to virtually "visit" their baby more often
      and give parents the feeling of control. A non-complex technical system like
      Telebaby is easily adopted by the parents, implementing it in a closed
      environment like a hospital is the real challenge.

PMID- 15460688
TI  - ASISTASTM telematic assistance for chronic asthma.
AB  - The paper presents a system developed for the assistance of diagnosis and
      treatment of chronic asthma. The system, named ASISTASTM, is a result of an
      interdisciplinary cooperation and is designed for the physician non specialist in
      the field of chronic obstructive pulmonary diseases. The ASISTASTM system offers
      assistance for the medical act in finding, diagnosing, establishing the
      therapeutic conduct, tracking over a period of time and hospitalizing the asthma
      patient ans aims to construct a better patient-medical service provider
      relationship by use of smart cards for patient's identification and usage of the
      facilites offered by the Internet.

PMID- 15460689
TI  - Comparing concepts for electronic health record architectures.
AB  - Keeping all relevant information directly or indirectly related to patient's
      care, electronic health records (EHR) systems are supposed to be kernel
      application for any kind of health information systems. For facilitating shared
      care, managed care, or disease management, such EHR systems have to be scalable,
      portable, distributed, and interoperable which has to be enabled by a proper
      architecture supporting informational and functional needs as well. Advanced EHR
      architectures are based on object-oriented or component-oriented paradigms and
      use modern tooling to design, specify, implement and maintain EHR solutions. They
      reflect not only medical information but also underlying concepts and integrate
      an extended vocabulary. The most advanced EHR architecture approaches CEN ENV
      13606, G-CPR, HL7 RIM and derived models, and finally the Australian GEHR project
      are shortly characterised. For comparing the solutions, the ISO RM - ODP, the
      Generic Component Model and the CORBA 3 methodology have been used. The HARP
      methodology for enhancing the current harmonisation of openEHR is shortly
      discussed.

PMID- 15460690
TI  - Setting up a common architecture for EPR in primary care: the Belgian experience.
AB  - A couple of years ago, the Belgian Federal Ministry of Health decided to back the
      development of a basic conceptual model for Electronic Patient Record (EPR) in
      primary care. Using consensus and modeling relational techniques, a working group
      of experts and experienced practitioners identified 7 key structuring concepts:
      Health Care Element, Health Approach, Contact, Subcontact, Service, Health Agent,
      Period. This model could roughly be seen as a restrictive sub-model of the
      current CEN proposal (prENV 13940) or as a first step to assess this CEN pre-Norm
      in Belgium. The conceptual model is already used in teaching activities and in a
      Belgian software labeling process.

PMID- 15460691
TI  - An architecture for a virtual electronic health record.
AB  - The Healthcare Domain Taskforce of the Object Management Group has specified
      standards for secure access and retrieval of demographic and medical data. This
      paper discusses the strengths and weaknesses of an electronic healthcare record
      that implements these specifications.

PMID- 15460692
TI  - A comparative study of EPR projects in Denmark.
AB  - The EPR-Observatory--a public funded project organization--has monitored Danish
      EPR-projects with respect to various parameters such as diffusion and diffusion
      rate, barriers and limitations, experience gained. Furthermore, the Observatory
      has aggregated and disseminated the results and has established a constructive
      dialogue between the Danish EPR projects. The Observatory has also focused in the
      later years on analysis of common frames of reference for EPR systems. The
      National Board of Health and some of the larger counties have developed such
      frames. First generation systems have been implemented in a few counties with
      moderate coverage, but a number of projects developing second generation systems
      are making progress, and the market situation is quickly maturing. There are
      still, however, major problems in the practical implementation of the systems.

PMID- 15460693
TI  - Comparing nursing terms from patient records to the ICNP, beta version.
AB  - Information about patient care is documented in order to promote continuous care
      and outcomes evaluation. With the computer advent in the healthcare area,
      standards documentation became mandatory. Many vocabularies are being developed,
      however, they are still insufficient to support clinical documentation. This
      study investigated the words used to document inpatients clinical assessment.
      These words were mapped into the International Classification for Nursing
      Practice (ICNP). The mapping process showed that only 247 words from 761 selected
      were included into the classification. Consequently, improvements have to done to
      facilitate the use of standard terminologies in the practice to improve the
      documentation itself.

PMID- 15460694
TI  - Optimizing coding quality: the role of the electronic medical record in the
      context of diagnosis related groups.
AB  - In 2003, a new prospective payment system will be introduced in Germany, which is
      based on the Australian Refined Diagnosis related Groups (AR-DRGs). Physicians
      must code diagnoses and procedures themselves. Inaccurately or incompletely coded
      patient records can result in considerable underpayment, so enhancing physicians'
      coding compliance and competence seems crucial. Coding shall be well integrated
      in the electronic patient record, providing a simple interface with background
      information, which is invoked out of the clinical documentation. This paper
      describes an existing implementation and possible further development.

PMID- 15460695
TI  - Text retrieval based on medical subwords.
AB  - In biomedical documents, there is ample evidence for complex morphological
      structures in specialized terms. While inflection is relatively easy to deal
      with, productive morphological processes such as derivation and single-word
      composition constitute a major challenge. Considering the problem from an
      information retrieval perspective, we split morphologically complex words into
      biomedically significant, morpheme-like subwords and match subwords the query
      terms and document terms are composed of. This way, morphologically motivated
      word form alterations can be eliminated from the retrieval procedure. Based on a
      series of retrieval experiments, we have gathered evidence that subword-based
      indexing and retrieval for the German biomedical sublanguage, at least-
      outperforms conventional string matching approaches.

PMID- 15460696
TI  - A web-based central diagnostic data repository.
AB  - A central repository for diagnostic information about individual patients was
      created as a service to diagnostic laboratories participating in the Compentence
      Network for Acute and Chronic Leukemias in order to support health care delivery
      to patients suffering from leukemia. During the diagnostic phase several
      specialised laboratories perform different assays on samples from the same
      patient. The use of these assays in the diagnostic process and during the
      treatment phase may be improved in terms of both rapid delivery and cost if any
      one laboratory is aware of preliminary or final results from the assay carried
      out in other laboratories. In order to support a more efficient communication of
      these results, a central diagnostic data repository (CDDR) was created and web
      based user interface was developed. Currently, the CDDR maintains documents in
      the form of portable document format (PDF) files. Several other formats are
      accepted and converted automatically upon entry. Patient identification is
      accomplished by pseudonym rather than proper name and the data is held on the
      CDDR for a limited time interval to accommodate the stringent privacy regulations
      in Germany. The principle operation of a CDDR may also be applied to the
      diagnostic or therapeutic process of other diseases.

PMID- 15460697
TI  - Knowledge engineering for a database between botany and art.
AB  - We present the knowledge organisation of a database, which aims to collect
      information for the project "Plants in European Masterpieces". This project is
      financed by the European Union within the Culture 2000 program. The project is
      aimed to link art with plants within the frame of a common European history and
      to make it accessible to a wide public. The informatics aspect of this project is
      focused on the creation of a data base which collects detailed information on
      selected plants and masterpieces in which these plants are presented. The main
      efforts in the design phase have been devoted to knowledge organisation in order
      to retain the taxonomic structure of the botanical knowledge, and to minimise
      data structure redundancies by linking some features which can be applied to the
      plants at different levels of their taxonomy to the correct level without
      repeating it. At present the database is installed in the Pc of all the experts
      that in the 5 involved countries collaborate to collect data for this project.
      This data is weekly merged in a central database, using a specific automatic
      procedure that avoids possible duplications of data inserted and checks for
      possible inconsistencies among data inserted in different temporal databases. The
      multi-language and easy to use features of this data base make it an interesting
      prototype for the spreading of scientific information to common public

PMID- 15460698
TI  - Guideline based structured documentation: the final goal?
AB  - Structured documentation of medical procedures facilitates information retrieval
      for research and therapy and may help to improve patient care. Most medical
      documents until today however consist mainly of unstructured narrative text. Here
      we present an application for endoscopy which is not only fully integrated into a
      comprehensive clinical information system, but which also supports various
      degrees of structuring examination reports. The application is used routinely in
      a German University hospital since summer 2000. We present the first unstructured
      version which permits storage of a free text report together with selected
      examination images. The next step added improved structure to the document using
      a catalogue of index terms. The practical advantages of selective patient
      retrieval are described. Today we use a version which supports fully structured,
      guideline based documentation of endoscopy reports in order to automatically
      generate essential classification codes and the narrative examination report All
      versions have advantages and disadvantages and we conclude that guideline based
      documentation may not be suitable for all endoscopy cases.

PMID- 15460699
TI  - Towards a PropeR combination of patient records and protocols.
AB  - The combination of a computer-based patient record system with a decision support
      system may give physicians the decisive push they need to accept such systems. In
      the PropeR-project we determine the requirements for a generic interface between
      both such systems and measure its potential impact on patient care. In this
      overview we describe the objectives, the experimental approach, and the current
      state of the PropeR-project. We also discuss the original positions behind the
      project.

PMID- 15460700
TI  - Development of electronic form of the 1999 WHO/ISH hypertension guidelines.
AB  - An electronic form of 1999 ISH/WHO Guidelines for Management of Hypertension was
      developed. It concentrates on two main problems--assessment of a patient's
      cardiovascular risk and selecting drug treatment. Moreover, it can remind the
      risk of unfilled items both for a cardiovascular risk calculation and drug
      contraindications. It can be stored for comparison with other records from follow
      up both in an electronic and paper form.

PMID- 15460701
TI  - A problem-oriented, knowledge-based patient record system.
AB  - The concept of a problem-oriented patient record was presented in the late 1960s
      but has yet to gain wide acceptance. In this paper we suggest a distinction
      between the idea of problem orientation and the implementation of the idea. We
      argue that the problem-oriented patient record offers an intuitive and useful way
      to work with patient information. We show that the concept of problem-oriented
      patient records facilitates better care of patients by supporting continuity of
      care, removing redundant and confusing information, and enabling easy overview of
      and access to its content. We further propose a two-layer framework that has
      knowledge of its content and use and is able to better utilize information in the
      record by presenting relevant information to the user at a time when needed.
      Conceptually, this is done by adding a layer of knowledge to the patient record
      system: 1) Knowledge about physicians' way of thinking and working, 2) Their
      corresponding information use and need during patient care, and 3) Tools to
      determine information relevance in a given situation; such a knowledge-based
      system is able to reason with its content and use.

PMID- 15460702
TI  - The Cadmio XML healthcare record.
AB  - The management of clinical data is a complex task. Patient related information
      reported in patient folders is a set of heterogeneous and structured data
      accessed by different users having different goals (in local or geographical
      networks). XML language provides a mechanism for describing, manipulating, and
      visualising structured data in web-based applications. XML ensures that the
      structured data is managed in a uniform and transparent manner independently from
      the applications and their providers guaranteeing some interoperability.
      Extracting data from the healthcare record and structuring them according to XML
      makes the data available through browsers. The MIC/MIE model (Medical Information
      Category/Medical Information Elements), which allows the definition and
      management of healthcare records and used in CADMIO, a HISA based project, is
      described in this paper, using XML for allowing the data to be visualised through
      web browsers.

PMID- 15460703
TI  - A networked electronic patient record system for diabetes.
AB  - This paper describes the development and clinical implementation of the
      SincroDiab--a synchronized diabetes register for the routine clinical practice in
      a LAN and for design of long-term trials and epidemiological studies based on the
      GEHR (Good European Health Record) architecture. The objectives of the SincroDiab
      system were to address the need to establish a more efficient and more effective
      information infrastructure to improve the ability to share patient record
      information among health care providers, to reduce the health care delivery
      costs, to meet the requirements of legal, regulatory or accreditation standards,
      to share comparable patients data among different sites within a multi-entity
      health care delivery system and to improve quality of care by network connecting
      the data repository to clinical workstations and departmental systems.

PMID- 15460704
TI  - Interoperable computerized smart card based system for health insurance and
      health services applied in cardiology.
AB  - In 1999 Romania started its health care reform by promulgating the Health
      Insurance Law. A functional and efficient health care system needs procedures for
      monitoring and evaluation of the medical services, communication between
      different service providers and entities involved in the system, integration and
      availability of the information. The final goal is a good response to the needs
      and demands of the patients and of the real life. For this project we took into
      account, on one hand, the immediate need for computerized systems for the health
      care providers and, on the other hand, the large number of trials and experiments
      with health smart cards across Europe. Our project will implement a management
      system based on electronic patient records to be used in all cardiology clinics
      and will experiment the health smart cards, will promote and demonstrate the
      capabilities of the smart card technology. We focused our attention towards a
      specific and also critical category of patients, those with heart diseases, and
      also towards a critical sector of the health care system--the emergency care. The
      patient card was tested on a number of 150 patients at a cardiology clinic in
      Bucharest. This was the first trial of a health smart card in Romania.

PMID- 15460705
TI  - Akteonline-an electronic healthcare record as a medium for information and
      communication.
AB  - The functionality of a personal Electronic Healthcare Record (EHR) may vary from
      a simple web-based interface for interactive data entry and data review up to a
      much more powerful system additionally supporting electronic data/document
      communication between clinical information systems of primary care practitioners
      or hospitals and even reminder based support for the empowered citizen, to
      actively take care of his health, based on relevant disease management programs.
      It is one means to support patient empowerment. Since storage and communication
      of data in an EHR comprises sensible personal health data, each of those
      functions need specific security and access management requirements to be
      considered and implemented.

PMID- 15460706
TI  - Developing a virtual patient record as a web-based workflow system.
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 systems bring this collaboration and cooperation into effect by
      automatically routing the medical information needed to authorized actors in a
      healthcare process. This paper presents a virtual patient record framework that
      allows integrating geographically dispersed medical information within a health
      district and enhancing collaboration and coordination of authorized workgroups by
      means of a web-based workflow system. An implementation of the proposed framework
      is also presented.

PMID- 15460707
TI  - Patient's permanent identification and PMSI chaining system. Complementary or
      competing methods?
AB  - In order to "chain" all the information concerning their patients' files,
      hospitals have set up their own identification system. This system is not easy to
      manage and can encounter several difficulties. When entering the hospital, each
      patient is given an identification number resulting mainly from his ID card, his
      Health Care card data and other data... The clerk who registers a patient seeks
      for possible prior hospital stays of this patient: should the patient be unknown,
      a new record of identification will be created; but should this patient be
      already registered, the clerk will link the patient's new hospital stay to the
      already existing file and update the permanent patient's identification data if
      necessary. In spite of all the care taken to carry out this process, some errors
      may occur: creation of "doubles", which means creating a new patient's file for
      an already existing patient, or conversely wrong chaining for an already existing
      patient. In order to track down these kinds of errors hospitals have set up a
      quality system. Moreover, since January 2001, in the frame of the Prospective
      Payment System (in French PMSI), a hospital stay chaining system based on a
      calculated key (H coding) has been designed. If the use of this key is meant to
      provide statistics concerning patients' cares and not patients' stays it may also
      become part of the quality policy of an establishment concerning patients'
      permanent identification data. Considering the 61 486 hospital stays at the C.H.U
      of Nancy for the first six months in 2001, it has been possible to compare the
      results in term of a patient population calculated from the permanent
      identification system of the hospital with the results obtained by the PMSI
      chaining system. No important differences have been detected and the results are
      very close. Besides, in order to track down possible doubles in the C.H.U patient
      identification system, chaining differences have been analysed. For the 22
      detected cases, no identification management anomalies can be found; the doubles
      are the result of the calculating system of the chaining key used by the PMSI. A
      single interesting case can be mentioned: it concerns an anonymous registration
      stay; despite a previous stay in the hospital, the patient was given another
      identification number to ensure her complete confidentiality.

PMID- 15460708
TI  - Implementation of a publication-subscription environment within a multi-agents
      paradigm.
AB  - Information management are workflow are one of the most important challenges to
      be met in hospitals. This challenge is even more important when having to deal
      with getting the right information at the right place, including such tools as
      alerts and notification. Open distributed intelligent agents constitute one of
      the most promising ways to explore, providing both ability to work in
      heterogeneous environment, and dealing with highly structured semantic knowledge.
      The paradigm proposed in this work is to consider a publication/subscription
      system as collaborative procedures network organized in workflows modelled by
      Petri nets. Each stage of workflow is carried out by a set of agent units having
      placed their competences in a workspace with a semantic description. Finally,
      robustness and tolerance are implicit properties of such agents; two mandatory
      characteristics of healthcare information systems.

PMID- 15460709
TI  - Consistency and reproducibility of attribute extraction by different machine
      learning systems.
AB  - Machine learning systems as tools for intelligent data analysis are used for
      extracting attributes relevant for prediction of defined outcomes. The aim of the
      paper was to compare two machine learning (ML) systems and propose method for
      intra- and inter-testing of consistency and reproducibility in attributes
      extracted from real dataset. See5 and FMLS extracted relevant attributes from
      real medical dataset. Comparison of results of both systems shows that: accuracy
      and sensitivity are nearly the same for both FMLS and See5 when FMLS was forced
      by attributes extracted by See5, and little bit lower when FMLS used its own
      extracted attributes; specificity is nearly the same for both FMLS and See5 when
      FMLS was forced by attributes extracted by See5, and much more higher when FMLS
      used its own extracted attributes; both of ML systems show intra-testing
      consistency and does not show any inter-testing consistency.

PMID- 15460710
TI  - A one-step approach to data retrieval, analysis and documentation.
AB  - In this paper we propose a system architecture to support data retrieval from
      patient records, together with data analysis, and report generation. Moving from
      retrieval all the way to documentation should be done as in a pipeline, and
      computer support must minimize manual steps in this knowledge refinement
      scenario. A case study is drawn from urology for surgery on patients with lower
      urinary tract symptoms.

PMID- 15460711
TI  - Retrieval of brain CT reports and images using interaction information retrieval.
AB  - The application of Interaction Information Retrieval to retrieve brain CT images
      is presented. After describing briefly the method and the architecture of the Web
      application, experimental results are reported and discussed.

PMID- 15460712
TI  - Data mining server--on-line knowledge induction tool.
AB  - The aim of this paper is to present an on-line data mining tool and illustrate
      its use on example of real medical data. Data from the Laboratory for in-vitro
      Thyroid diagnostics at the Sisters of Charity University Hospital in Zagreb were
      used. Preparation of the data set and one session of knowledge induction is
      described.

PMID- 15460713
TI  - Leveraging intelligent agents for knowledge discovery from heterogeneous
      healthcare data repositories.
AB  - This paper presents a case for an intelligent agent based framework for knowledge
      discovery in a distributed healthcare environment comprising multiple
      heterogeneous healthcare data repositories. Data-mediated knowledge discovery,
      especially from multiple heterogeneous data resources, is a tedious process and
      imposes significant operational constraints on end-users. We demonstrate that
      autonomous, reactive and proactive intelligent agents provide an opportunity to
      generate end-user oriented, packaged, value-added decision-support/strategic
      planning services for healthcare professionals, manages and policy makers,
      without the need for a priori technical knowledge. Since effective healthcare is
      grounded in good communication, experience sharing, continuous learning and
      proactive actions, we use intelligent agents to implement an Agent based Data
      Mining Infostructure that provides a suite of healthcare-oriented decision
      support/strategic planning services.

PMID- 15460714
TI  - Data security and protection in cross-institutional electronic patient records.
AB  - This paper describes data protection and data security requirements of a cross
      institutional electronic patient record, and presents possible solutions for
      meeting these requirements. A comprehensive analysis of literature and legal
      documents was performed. Beside the general requirements that the EPR of a single
      institution must meet, specific requirements exist for cross-institutional EPRs.
      In Germany, patient information may only be revealed to external physicians
      within so-called "treatment connections". A secure connection between the EPR
      systems of two health institutions in Germany, which jointly treat tumor
      patients, was established using additional SecuRemote Software. The development
      and implementation of a cross-institutional EPR is a complicated process, mainly
      due to data security regulations. However, its introduction is thought to be
      valuable, since a cross-institutional EPR will improve communication within
      shared care processes, and, thus, improve the quality of patient care.

PMID- 15460715
TI  - Access control administration in healthcare applications.
AB  - The interconnection of information systems of different parties involved in
      healthcare applications leads to the need for information sharing across large
      scale and highly distributed database systems. Applying appropriate access
      control policies in an effective and flexible way is a specific task for a number
      of local security officers that must operate according to a high-level access
      control administration system. The particular security requirements of healthcare
      information systems are reflected to the access control system, which must be
      flexible and dynamically adaptable to the daily activities. Decentralizing access
      control administration can be achieved in a uniform and consistent way when
      applying appropriate administrative rules and constraints. In this paper are
      presented the basic features of an access control administration model for
      interconnected information systems, as in the healthcare environment.

PMID- 15460716
TI  - Security in the French-speaking Virtual Medical University.
AB  - The Medical Virtual French-Speaking University (UMVF) is a government sponsored
      program. The participating medical schools will share Web accessible scientific
      contents and develop their own teaching strategies and learner-trainer
      interactions. An e-learning platform will manage the access to the UMVF and its
      various resources. This access will require a unique
      identification/authentication. Users will then be guided toward those resources
      adapted to their profile. We recommend the use of a smart card for the
      identification/authentication. The connection should be secured via a SSL
      protocol when using critical resources such as assessment of a student,
      discussion between a student and a teacher and creation or modification of
      resources by a teacher. In other cases, secure connection will not be required.
      Usage rights of resources will be explicated. Critical data will be ciphered.

PMID- 15460717
TI  - Development of universal electronic health record in cardiology.
AB  - In the paper we discuss the vision and experiences in development of electronic
      health record based on universal structure of collectable data, multimedia
      objects, all equipped by supporting systems for data verification and medical
      guidelines connection. This development is based on existing European and
      international standards in the field of medical informatics.

PMID- 15460718
TI  - Electronic patient record for N.N. Burdenko Neurosurgical Institute: on the road
      to paperless patient record.
AB  - The paper is devoted to one of a number of highways of medical informatics: a
      road from traditional paper patient record (PPR) to future paperless patient
      record (PLPR). This road runs via modem electronic patient record (EPR), usually
      blending together electronic and paper technologies of gathering, storing,
      retrieving, presentation and legalization of data. The following is based on the
      experience of modelling, engineering, deployment, support and evolution of
      electronic patient record for N.N. Burdenko neurosurgical institute. Three basic
      facets of the problem will be discussed: technological, psychological and legal.

PMID- 15460719
TI  - Electronic patient records: Dutch domain information model perinatology.
AB  - Currently a national domain information model is developed to support information
      exchange via electronic patient records (EPR), and to support the adoption of the
      EPR in Dutch healthcare practice. This article describes a pilot for the domain
      information model for mother- and childcare (perinatology) that serves as a first
      'use case'. The 'use case' is modeled using the Health Level 7 version 3
      Reference Information Model (HL7 RIM) as the methodology and modeling tool. The
      first results are promising, despite the fact that HL7 RIM is still in a draft
      version up to formal vote. The models of the 'use case' are both specific and
      generic at the same time, allowing professionals to recognize their domain
      specific content and work, and the EPR developers, or developers of messages for
      information exchange, to build practical implementations. The approach bridges
      professional content and technical issues.

PMID- 15460720
TI  - A new method for matching a document to potential users' information needs.
AB  - This paper explores approach to finding out how the information needs that a
      document can address can be captured. This is important in order to improve
      indexing strategies applied to document collections. We propose and implemented a
      cognitive science approach, the "jeopardy game" method of evaluation combined
      with "think aloud" analysis. The results of the demonstration study are presented
      and discussed. Some possible improvements to the method for matching a document
      to potential users' information needs are identified.

PMID- 15460721
TI  - Are quantitative methods sufficient to show why wards react differently to
      computer-based nursing documentation?
AB  - Computer-based documentation of the nursing process is being introduced into
      hospitals more and more. Frequently, the introduction is followed by an
      evaluation of positive and negative effects. However, the often-used quantitative
      evaluation methods cannot fully illuminate the different success factors of
      computer-based nursing documentation systems. We introduced a computer-based
      nursing documentation system on four wards of the University Medical Centre of
      Heidelberg and systematically evaluated its effects in a two-year study. The
      quantitative analysis of the results showed that the wards reacted differently to
      the documentation system. In this paper, we will first take a look at the
      quantitative results of our evaluation study, and will then discuss possible
      reasons for the detected differences. We will then argue that only qualitative
      methods can help to fully reveal both expected and unexpected reasons for
      differences between the wards. Analysing the reasons for the different reactions
      will help lead to a better understanding of the factors that lead influence the
      successful introduction of a computer-based nursing documentation system. Both
      quantitative analysis and qualitative analysis have a role in this information
      system evaluation.

PMID- 15460722
TI  - Combining voice recognition and automatic indexing of medical reports.
AB  - Medical records have been evolving from the traditional paper-based records to
      digital ones, from the method of dictating reports and transcription to voice
      recognition systems. The transition to digital operations will not be complete
      until we have the ability to combine voice recognition with automated indexing of
      texts. This paper introduces the methods we used to evaluate existing voice
      recognition software programs and presents NOMINDEX, a system that turns a
      medical text into MeSH codes, using the French ADM lexical database. Those
      systems were applied to 28 patient discharge summaries in French, produced after
      a coronarography, and extracted from the MENELAS corpus of texts. Using the best
      configuration for voice recognition, the rate of accurate recognition exceeds 98
      percent. Among the indexing concepts assigned by NOMINDEX, 25 percent were not
      pertinent and 12 percent of the relevant concepts were missing. Most errors were
      related to confusion between common language and medical language, and to the
      coverage of the ADM lexical database. Best results would be expected with a more
      comprehensive lexical resource In addition, only 3 percent of the errors
      generated by inadequate voice recognition that remained in the configuration that
      performed better, impacted on automatic indexing by NOMINDEX.

PMID- 15460723
TI  - Automatic conceptual indexing of French pharmaceutical theses.
AB  - French pharmaceutical theses are rarely quoted. If the main obstacles originate
      from language or access barriers, proper indexation could also be blamed.
      Manually extracted key-words don't necessary come from a structured thesaurus. In
      the following work, this manual indexing method is compared to an automated one,
      "Nomindex", based on UMLS. The automated method is improved by the addition of a
      relevance scoring system. The first indexing step consists of downloading,
      adapting and indexing theses in electronic format. Results will then be analyzed
      and sorted by relevance, through the comparison of classic statistical indices
      (noise, silence and relevance). It was assumed that the manually obtained key
      words were always relevant. The silence of manual indexing is nevertheless high:
      seven new key-words are proposed by Nomindex, which results are mixed (10% of
      silence, but 50% of noise). These results are promising on the first experiment
      on pharmaceutical document without lexicon improvement. The indexing, if it is
      currently insufficient for a real life use, could easily be improved by specific
      updates of the lexicon.

PMID- 15460724
TI  - Breath Multi Analysis: a database to collect data on gastric related non invasive
      analysis.
AB  - The diagnosis of dyspepsia is very difficult because the symptoms are clinically
      aspecific and the gastric emptying time tests are of complex interpretation. An
      integrated and automated analysis of clinical and instrumental data may improve
      the diagnostic process. We present a system to collect data on dyspeptic patients
      from different sources which have been set up to assist the clinician in the
      diagnosis of dyspepsia. The data base integrates a wide set of symptoms with data
      coming from non invasive laboratory tests. Moreover, we assess the feasibility of
      considering the same methods for collecting data also for adsorption problems and
      for hepatic problems.

PMID- 15460725
TI  - Co-ordination between clinical coding systems and pragmatic clinical
      terminologies based on a core open system: the role of ISO/TC215/WG3 and
      CEN/TC2511/WG2 standardisation?
AB  - The article addresses the need to co-ordinate efforts to develop clinical coding
      systems and pragmatic clinical terminologies like SNOMED CT. In the first part, a
      description is given of the current context of divergent and replicated efforts.
      Then is presented a "reference terminology representation" approach based on a
      formal terminology representation as an open source available in the public
      domain with diversity in the linguistic expressiveness of end users let to
      competing developers and researchers. The last part is devoted to the
      contribution of the standardisation process in healthcare terminology initiated
      by CEN/TC251 and supported now by the work of CEN/TC215/WG3 to this new approach
      which can be summarised as the practical realisation of an ontology.

PMID- 15460726
TI  - Multilingual approach to ICD10: on the need for a source reference database.
AB  - The distribution of ICD10 is of concern for thousand of developers in numerous
      countries. The absence of some basic features to facilitate the transfer and
      consequently to augment the quality of the delivered version is a constant
      characteristic. Errors, ambiguities, missing terms, unrecognised attributes are
      quite common, despite the efforts of some national centres doing their best to
      fill this gap. For other countries and languages, where such centres do not exist
      or do not have sufficient resources, this problem is even stronger. A reference
      ICD database is clearly a need today. The following features are to be made
      available out of an ICD database: exact count of terms, whether they are
      systematic, include, exclude or daggers and asterisks pairs, eventually at
      chapter level; exact count of notes, references and indirect exclusions;
      recommended structure of relational tables for ICD representation; basic
      structure of the classification at any level of detail. These features are
      somewhat language dependant and should be repeated for each one. This paper
      demonstrates the benefits of publishing such ICD reference information in order
      to improve the future ICD tools to be developed in numerous countries.

PMID- 15460727
TI  - Shallow linguistic analysis of a large corpus of drug prescriptions.
AB  - We report on first experiences from linguistic analyses of patient instructions
      from 19,8404 actual drug prescriptions regarding seven pharmaceutical products
      frequently prescribed in Sweden. The analysis includes expressions for amount,
      dose unit, dose interval, mode of administration, purpose and a few further
      details. Even simple processing seems useful to extract information from these
      short, rather formal text strings. We estimate the potential for calculation of
      prescribed dose from this material, and collected material gives a good starting
      point for more advanced linguistic analyses.

PMID- 15460728
TI  - A controlled vocabulary for nursing practice and research.
AB  - The paper describes the process of evolving a controlled Nursing Vocabulary for
      indexing and information retrieval purposes. The vocabulary is based on terms of
      the thesaurus of Medline i.e. MeSH (Medical Subject Headings) by National Library
      of Medicine and the International Classification for Nursing Practice (ICNP) by
      the International Council of Nurses. The vocabulary consists of 10 themes central
      to nursing domain. The vocabulary is added as an independent theme to the Finnish
      thesaurus FinMeSH. The validity of the vocabulary has been tested for indexing
      nursing research once and has afterwards been revised. The validity will be
      tested again during spring 2002.

PMID- 15460729
TI  - Applying temporal abstraction and case-based reasoning to predict approaching
      influenza waves.
AB  - The goal of the TeCoMed project is to send early warnings against forthcoming
      waves or even epidemics of infectious diseases, especially of influenza, to
      interested practitioners, pharmacists etc. in the German federal state
      Mecklenburg-Western Pomerania. The forecast of these waves is based on written
      confirmations of unfitness for work of the main German health insurance company.
      Since influenza waves are difficult to predict because of their cyclic but not
      regular behaviour, statistical methods based on the computation of mean values
      are not helpful. Instead, we have developed a prognostic model that makes use of
      similar former courses. Our method combines Case-based Reasoning with Temporal
      Abstraction to decide whether early warning is appropriate.

PMID- 15460730
TI  - On distance computation in space of mixed-type variables in medical data mining.
AB  - In the next study we consider two distance metrics that were presented in the
      machine leaming literature for mixed-type variables. We show that they are not
      really metrics, but pseudometrics. The problem arose from missing values. The
      metrics can be redefined to satisfy the metricity definition. Distance
      computation can then be performed reliably without a possibility that a distance
      between exactly similar patient cases would not be zero. We experimented with
      both procedures and so-called ignore mode using two medical data sets and
      observed that the redefined procedure was as good as the original approach as
      measured with the classification ability of one-nearest neighbour searching. It
      is noticeable that the described problem caused by missing values can be with any
      distance measure if its missing values are treated in the pessimistic manner as
      in the original version of these distance measures.

PMID- 15460731
TI  - Cluster analysis of Wisconsin Breast Cancer dataset using self-organizing maps.
AB  - This work deals with multidimensional data analysis, precisely cluster analysis
      applied to a very well known dataset, the Wisconsin Breast Cancer dataset. After
      the introduction of the topics of the paper the cluster analysis concept is
      shortly explained and different methods of cluster analysis are compared.
      Further, the Kohonen model of self-organizing maps is briefly described together
      with an example and with explanations of how the cluster analysis can be
      performed using the maps. After describing the data set and the methodology used
      for the analysis we present the findings using textual as well as visual
      descriptions and conclude that the approach is a useful complement for assessing
      multidimensional data and that this dataset has been overused for automated
      decision benchmarking purposes, without a thorough analysis of the data it
      contains.

PMID- 15460732
TI  - Application of repeated measurement ANOVA models using SAS and SPSS: examination
      of the effect of intravenous lactate infusion in Alzheimer's disease.

PMID- 15460733
TI  - Analysis of the time series for some causes of death.
AB  - The mortality data may be analysed by time series methods such as autoregressive
      integrated moving average (ARIMA) modelling. This method is demonstrated by two
      examples: analysis of the mortality data of cerebrovascular diseases and analysis
      of the mortality data of cancer of cervix. Mathematical expressions are given for
      the results of analysis. The relationships between time series of mortality rates
      were studied with ARIMA models. Calculations of confidence intervals for
      autoregressive parameters by tree methods: standard normal distribution as
      estimation and estimation of the White's theory and the continuous time case
      estimation. Analysing the confidence intervals of the first order autoregressive
      parameters we may conclude that the confidence intervals were much smaller than
      other estimations by applying the continuous time estimation model.

PMID- 15460734
TI  - Automatic diagnosis classification of patient discharge letters.
AB  - CAIRN (Computer Assisted Medical Information Resource Navigation) is a
      prototyping System that allows flexible medical data storage and retrieval
      supporting medical informatics research. In this paper methods that automate the
      selection of ICD-9 diagnosis (International Classification of Diseases and
      Diagnoses, 9th Revision) are investigated. We present the Text Data Mining module
      extension of CAIRN and its application in order to organize in a systematic way
      uncontrolled terms, to propose relationships between uncontrolled terms and
      finally aid the diagnosis classification.

PMID- 15460735
TI  - Nearest neighbour classification of otoneurological data.
AB  - We studied the nearest neighbour classification of patient cases with benign
      positional vertigo, Meniere's disease, sudden deafness, traumatic vertigo,
      vestibular neuritis, and vestibular schwannoma. The classification results were
      compared to the inference results obtained by an otoneurological expert system
      ONE whose inference mechanism somewhat resembles the classical nearest neighbour
      method. With respect to the predictive accuracy, the classification results of
      these two systems agreed. The best predictive accuracy for the expert system ONE
      was 79.7% and for the nearest neighbour method 80.5%. However, differences in the
      true positive rates for sudden deafness, traumatic vertigo, vestibular neuritis,
      and vestibular schwannoma were found. The nearest neighbour classification
      results will be used in the refinement of ONE's knowledge base.

PMID- 15460736
TI  - Using n-gram method in the decomposition of compound medical diagnoses.
AB  - Compound diagnoses are often assigned to just one disease code. This is a known
      cause of coding error. Our paper outlines an efficient, cheap and easy to
      implement method for semi-atutomatic decomposition of such diagnostic
      expressions. The proposed method is based on n-grams. To verify the method two
      human encoders were asked to analyse the same set of 92 clinical diagnoses. Their
      results were compared to the analysis produced by the method. The results
      demonstrate the reasonability of the approach.

PMID- 15460737
TI  - Using text generation to access clinical data in a variety of contexts.
AB  - MedView is a joint project with participants from oral medicine and computer
      science. The aim of the project is to build a large database from patient
      examinations and produce computerised tools to access data in various ways. One
      way to access data is to read case descriptions generated from stored cases. We
      give a description of how documents are generated from data and how these are
      used in a variety of contexts to supply useful information.

PMID- 15460738
TI  - Supporting clinical practice guidelines: lifecycle of guidelines for oncology
      within an XML-based guideline framework.
AB  - Clinical Practice Guidelines (CPGs) have become important instruments for
      supporting patient care. Many structure models for CPGs have been developed to
      explicitly gain structured CPG documents, some of them using XML. Often, however,
      problems arise in filling these structures with content and integrating CPG
      applications into an EPR/HIS The Universities of Giessen and Heidelberg have each
      presented an XML-based CPG structure, which are actually being merged into one.
      The obtained CPG structure will build our common "xCPG core model" embedded in an
      "XML framework", an authoring environment. This paper shows how this model used
      in the framework could support the entire 5-step CPG lifecycle, spanning CPG
      development, the integration of a CPG into an EPR/HIS, as well as maintenance.
      Furthermore, this paper points out how the method draws on the different
      information management services as a precondition for successful CPG
      implementation.

PMID- 15460739
TI  - Representing clinical guidelines in UMl: a comparative study.
AB  - Clinical guidelines can be represented using models, such as GLIF, specifically
      designed for healthcare guidelines. This paper demonstrates that they can also be
      modelled using a mainstream business modelling language such as UML. The paper
      presents a guideline in GLIF and as UML activity diagrams, and then presents a
      mapping of GLIF primitives to UML. The potential benefits of using a mainstream
      modelling language are outlined. These include availability of advanced modelling
      tools, transfer between modelling tools, and automation via business workflow
      technology.

PMID- 15460740
TI  - Remodeling of legacy systems in health care using UML.
AB  - Research projects in the field of Medical Informatics often involve the
      development of application systems. Usually they are developed over a longer
      period of time, so that at a certain point of time a systematically planned
      reimplementation is necessary. The first step of reimplementation should be a
      systematic and comprehensive remodeling. When using UML for this task a
      systematic approach for remodeling activities is missing. Therefore, we developed
      a method for remodeling of legacy systems (Qumquad) and applied it to DOSPO, a
      documentation and therapy planning system for pediatric oncology. Qumquad helps
      to systematically carry out three steps: the modeling of the current actual state
      of the application system, the systematic identification of weak points and the
      development of a target concept for reimplementation considering the identified
      weak points. Results show that this approach is valuable and feasible and could
      be applied to various application systems in health care.

PMID- 15460741
TI  - Why continuity of care needs computing--results of a quantitative document
      analysis.
AB  - With the increasing practice of early discharges from hospital continuity of care
      is attaining new attention. Although communication gaps including incomplete and
      delayed information are well known the vast majority of discharge summaries are
      still paperbased. The question of this study was whether The medium paperbased
      discharge form can be structured and complete enough to overcome the
      communication deficits. All 32 different types of nursing discharge forms
      analysed suffered from a compromise between structure, content and space. None of
      the forms allowed for a complete documentation of the nursing process. Only the
      minority of forms offered the complete set of activities of daily living to be
      checked. Most of the forms were designed only by one sector without any
      provisions for different terminologies and needs across the sectors. It is
      concluded that these shortcomings can only be overcome by a dynamic and flexible
      instrument, ideally by an electronic discharge summary.

PMID- 15460742
TI  - Evaluation of a frame-based ontology: a formalization-oriented approach.
AB  - This paper describes the evaluation of our current frame-based ontology in
      Intensive Care. Our approach to the evaluation consists of formalizing the
      ontology. The motivation for formalization is twofold: a. The formalization
      process itself can shed light on the implicit ambiguities in the ontology and b.
      The result of this process is a representation that facilitates automatic
      inference. The evaluation has revealed various ambiguities in the current
      ontology, and has clarified the path for migration towards a formal
      representation supporting automatic inference.

PMID- 15460743
TI  - Impact of data encoding and thyroids dysfunctions.
AB  - In medical environments it is usual to previously encode some variables following
      medical criteria. In the context of thyroids dysfunctions, the levels of the
      hormones T3, T4 or TSH are usually treated as low, normal or high instead of
      using their numerical form, and this is a very common practice in other items. In
      medical environments it is also frequent to need a clustering process to analyze
      data. Clus-tering algorithms use always some distance or similarity coefficient
      to decide which elements have to be grouped in a cluster. The nature of the data
      determines which distance/similarity can be used, and can change results. In this
      paper, the impact of preprocessing numerical levels of hormones into categorical
      labels for clustering is studied, by means of a real sample of patients from a
      Hospital in Zagreb (Croatia).

PMID- 15460744
TI  - Psychological questionnaires application and processing for detection of
      psychosomatic states of an operator.
AB  - This paper describes the method of detection of psychosomatic states of an
      operator. Understanding of these states can be used in closing of external human
      feedback. Detection uses psychological self-diagnostic questionnaires and is
      supported by experimentally gained data. The next approach of processing is
      designed by statistical methods and by methods of artificial intelligence.

PMID- 15460745
TI  - The 'cube' meta-model for the information system of large health sector
      organizations--a (platform neutral) mapping tool to integrate information system
      development with changing business functions and organizational development.
AB  - To develop information systems (IS) in the changing environment of the health
      sector, a simple but throughout model, avoiding the techno-jargon of informatics,
      might be useful for the top management. A platform neutral, extensible,
      transparent conceptual model should be established. Limitations of current
      methods lead to a simple, but comprehensive mapping, in the form of a three
      dimensional cube. The three 'orthogonal' views are (a) organization
      functionality, (b) organizational structures and (c) information technology. Each
      of the cube-sides is described according to its nature. This approach enables to
      define any kind of an IS component as a certain point/layer/domain of the cube
      and enables also the management to label all IS components independently form any
      supplier(s) and/or any specific platform. The model handles changes in
      organization structure, business functionality and the serving info-system
      independently form each other. Practical application extends to (a) planning
      complex, new ISs, (b) guiding development of multi-vendor, multi-site ISs, (c)
      supporting large-scale public procurement procedures and the contracting,
      implementation phase by establishing a platform neutral reference, (d) keeping an
      exhaustive inventory of an existing large-scale system, that handles non-tangible
      aspects of the IS.

PMID- 15460746
TI  - Toward a quantitative analysis of skin lesion images.
AB  - Melanoma is the most dangerous form of skin cancer. Skin cancers, and
      particularly melanomas, can be easily cured if detected early. The regularity of
      the pigment network structure is a significant sign for early diagnosis of
      melanoma. We present here a quantitative analysis of the morphology of the
      pigment network structure. Our method is based on the extraction of the pigment
      network structure using digital image processing techniques. Once the network is
      extracted, it is possible to derive statistical indicators relative to its
      regularity or irregularity. We report experiments on a database of 14 images,
      showing the effectiveness of our method.

PMID- 15460747
TI  - Patient empowerment and the asymmetry of knowledge.
AB  - eHealth consumers know more, expect more and demand more. The Inteernet has the
      potential of being a major influence on them by opening up vast opportunities for
      information transparency and access and the sharing of information which is
      essential to healthcare practice. But, these vast opportunities also pose
      numerous obstacles, such as the lack of common terminology or terminology
      standardization, the uncertain quality and reliability of the information on the
      Internet, the public's health literacy and the digital divide. A gradual and
      progressive shift from exclusive to shared knowledge and responsibility can be
      achieved by patient/physician collaboration.

PMID- 15460748
TI  - A strategy to enhance the usability of the minimal model as used with the
      intravenous glucose tolerance test in diabetes research and clinical management.
AB  - The Minimal Model method of determining Insulin Sensitivity from the Intravenous
      glucose Tolerance Test is a valuable tool for the Diabetes research community.
      However the Minimal Model algorithm itself is not readily available in a user
      friendly modem windows environment to the clinical researcher in many research
      departments. In addition use of the model often requires intervention by an
      experienced "modeller" to interpret the results produced by the method. This
      paper proposes a more readily available and usable version of the program and
      discusses the issues which surround the use of the program by clinical
      researchers without computer mathematical modelling experience.

PMID- 15460749
TI  - A case study on constructive assessment of bids to a call for tender.
AB  - A case study based on constructive assessment methodology is taking place at the
      purchase of a Laboratory Information System. The present report describes the
      strategy and approach for the selection process, together with some results and
      lessons learned, while a parallel paper presents the tools applied.

PMID- 15460750
TI  - Tools for constructive assessment of bids to a call for tender--some experiences.
AB  - The paper describes the experiences from a full-scale case study applying a
      number of novel assessment techniques for selecting among income bids at a call
      for tender, based on a User Requirements Document that comprises non
      prescriptive, goal-oriented requirements.

PMID- 15460751
TI  - Evaluation during design of a regional seamless network of social and health care
      services--information technology perspective.
AB  - This paper reports results from a constructive evaluation study where design of a
      reagional social and health care information system was assessed from information
      technology perspective. We studied the models of social and health care
      processes, the needs and requirements of the clients and users and the planned
      information system. Our results envision the importance to focus during the
      design on the service chain and process models, including strategic processes
      where the mission, vision and values of the organisation are represented. Also,
      the stakeholders' needs and requirements for the system need to be explicitly
      described and included as system functionalities and characteristics.
      Additionally, theoretical frameworks from health informatics are needed to
      understand the phenomenon under study, to build a model and to develop
      implementations and installations of the model in the social and health care
      organisational context.

PMID- 15460752
TI  - Impact of site-specific customizations on physician compliance with guidelines.
AB  - Developed and implemented in the Service d'Oncologie Medicale Pitie-Salpetriere
      (Paris, France) as a computer-based guideline system on breast cancer, OncoDoc
      has already demonstrated high physician compliance rates. To assess how the
      system could be reused in another institution which was not involved in the
      development process, we have conducted a new experimentation at the Institut
      Gustave Roussy. Minor site-specific customizations of the knowledge base have
      been performed. After four months, 127 cases were recorded. Results showed that
      there was no significant difference of physician compliance with OncoDoc (85%)
      when site-specific recommendations were, or not, available, although local
      recommendations were chosen preferably (55%), thus legitimating the adaptation.

PMID- 15460753
TI  - Guideline validation in multiple trauma care through business process modeling.
AB  - Clinical guidelines can improve the quality of care in multiple trauma. In our
      Department of Trauma Surgery a specific guideline is available paper-based as a
      set of flowcharts. This format is appropriate for the use by experienced
      physicians but insufficient for electronic support of learning, workflow and
      process optimization. A formal and logically consistent version represented with
      a standardized meta-model is necessary for automatic processing. In our project
      we transferred the paper-based into an electronic format and analyzed the
      structure with respect to formal errors. Several errors were detected in 7 error
      categories. The errors were corrected to reach a formal and logically consistent
      process model. In a second step the clinical content of the guideline was revised
      interactively using a process modeling tool. Our study reveals that guideline
      development should be assisted by process modeling tools, which check the content
      in comparison to a meta-model. The meta-model itself could support the domain
      experts in formulating their knowledge systematically. To assure sustainability
      of guideline development a representation independent of specific applications or
      specific provider is necessary. Then clinical guidelines could be used for
      training, process optimization and workflow management additionally.

PMID- 15460754
TI  - Performance evaluation of artificial intelligence classifiers for the medical
      domain.
AB  - The application of artificial intelligence systems is still not widespread in the
      medical field, however there is an increasing necessity for these to handle the
      surfeit of information available. One drawback to their implementation is the
      lack of criteria or guidelines for the evaluation of these systems. This is the
      primary issue in their acceptability to clinicians, who require them for decision
      support and therefore need evidence that these systems meet the special safety
      critical requirements of the domain. This paper shows evidence that the most
      prevalent form of intelligent system, neural networks, is generally not being
      evaluated rigorously regarding classification precision. A taxonomy of the types
      of evaluation tests that can be carried out, to gauge inherent performance of the
      outputs of intelligent systems has been assembled, and the results of this
      presented in a clear and concise form, which should be applicable to all
      intelligent classifiers for medicine.

PMID- 15460755
TI  - Assessing association rules and decision trees on analysis of diabetes data from
      the DiabCare program in France.
AB  - Recent advances in information technology have made it possible to solve
      increasingly complex problems, and also to collect and store huge amounts of
      information. These vast quantities of data further have to be transformed into
      relevant value-added and "decision-quality" knowledge. It is against this
      background that the KDD (Knowledge Discovery in Databases), a multidisciplinary
      field using computer learning, artificial intelligence, statistics, database
      technology, expert systems, and data visualization, appeared in the early 90's.
      In order to assess these technologies in the medical field, we have tested some
      of these techniques on a large database at our disposal, named DiabCare stemming
      from the WHO - DiabCare program for the application of the Saint-Vincent
      Declaration. It contains evaluation data on the health care of patients with
      diabetes, and in particular, its complications. So far, data analysis has been
      done using classical statistical methods, and we now intend to make use of such
      data-mining tools as Associations Rules and Decision and Classification Trees for
      further exploration of this database. The results presented here show that data
      mining techniques can be used successfully to extract knowledge from medical
      databases. The results obtained using Association Rules and especially Decision
      Trees are very promising.

PMID- 15460756
TI  - An integrated knowledge management system for the clinical laboratories: an
      initial application of an architectural model.
AB  - eLABook is a web-distributed knowledge management system designed to support the
      needs of clinicians and laboratory staff in the selection and interpretation of
      investigations in laboratory medicine. Access can be by hyperlinks at any point
      through the request-report cycle, by browsing down a hierarchy, and by various
      search approaches. The information describes service issues, which are
      predominantly locally determined, and clinical implications, which may be local,
      national, governmental and international. The application has been implemented
      across the Oxford Clinical Intranet to support secondary care in the four
      hospital sites of the Oxford Radcliffe Hospitals and by general practitioners in
      Oxfordshire. The knowledge base is capable of rapid changes in response to input
      from both developers and users. It supports authoring, editing and a full audit
      trail of changes. The selected architecture allows very large scale hierarchical
      structures and is designed to accommodate future needs for an object-distributed
      processing deployment.

PMID- 15460757
TI  - Clinical decision support system in dementia care.
AB  - In this paper we present a prototype system as a tool for clinical decision
      support in the domain of cognitive diseases. The number of patients is increasing
      while the number of patients that the general practitioner (GP) meets in primary
      care still is too low to make the GP well trained in diagnostics and management
      of patients in the area of cognitive diseases. In addition, new treatment
      strategies are established in clinical routine directed towards cognitive
      deficiencies with behavioural and psychological symptoms in the presence of
      dementia (BPSD).

PMID- 15460758
TI  - Computer aided interactive remote diagnosis of Parkinsonians.
AB  - We develop a diagnostic tool to support the objective diagnosis of Parkinsonians.
      We suggest a cost and time efficient diagnostic tool: patients may complete
      exercises using a personal computer at home and the data is gathered for further
      studies via Internet in a central database.

PMID- 15460759
TI  - MedView: a declarative approach to evidence-based medicine.
AB  - MedView is a project that meets the challenges of evidence-based oral medicine by
      providing a formalisation of clinical examination data and clinical procedures.
      Tools are provided for knowledge acquisition, knowledge generation, visualisation
      and analysis of data, and knowledge sharing. The formal declarative model
      constitutes the main governing principle in MedView, not only in the
      formalisation of clinical terms and concepts, but in visualisation models and in
      the design and implementation of individual tools and the system as a whole as
      well.

PMID- 15460760
TI  - MedRapid--medical community & business intelligence system.
AB  - OBJECTIVE: currently, it takes at least 6 months for researchers to communicate
      their results. This delay is caused (a) by partial lacks of machine support for
      both representation as well as communication and (b) by media breaks during the
      communication process. METHODS: To make an integrated communication between
      researchers and practitioners possible, a general structure for medical content
      representation has been set up. The procedure for data entry and quality
      management has been generalized and implemented in a web-based authoring system.
      RESULTS: The MedRapid-system supports the medical experts in entering their
      knowledge into a database. Here, the level of detail is still below that of
      current medical guidelines representation. However, the symmetric structure for
      an area-wide medical knowledge representation is highly retrievable and thus can
      quickly be communicated into daily routine for the improvement of the treatment
      quality. In addition, other sources like journal articles and medical guidelines
      can be references within the MedRapid-system and thus be communicated into daily
      routine. CONCLUSIONS: The fundamental system for the representation of medical
      reference knowledge (from reference works/books) itself is not sufficient for the
      friction-less communication amongst medical staff. Rather, the process of (a)
      representing medical knowledge, (b) refereeing the represented knowledge, (c)
      communicating the represented knowledge, and (d) retrieving the represented
      knowledge has to be unified. MedRapid will soon support the whole process on one
      server system.

PMID- 15460761
TI  - A web-based randomisation service for clinical studies.
AB  - The Competence Network for Acute and Chronic Leukemias is one of several networks
      of competence, each directed at a specific disease. Within this context, a web
      based randomisation service was designed and implemented as a service to
      participating study groups. It provides centralised randomisation for several
      study centres that is independent of each of the centres. In order to minimise
      difficulties in using this service arising from the fact that it is only needed
      fairly infrequently, the user interface was kept as simple as possible. The major
      advantages of a web-based service lie in its "unpredictability" and its
      continuous availability at all times without the need for around-the-clock
      personnel. The experience gained with this service in the context of the
      Competence Network with a relatively small number of actual users may provide the
      basis for a more widespread application.

PMID- 15460762
TI  - Step-by-step mark-up of medical guideline documents.
AB  - The quality of document-centric formalisation of medical guidelines can be
      improved using a decomposition of the whole process into several explicit steps.
      We present a methodology and a software tool supporting the step-by-step
      formalisation process. The knowledge elements can be marked up in the text with
      increasing level of detail, rearranged into an XML knowledge base and exported
      into the operational representation. Semi-automated transitions can be specified
      by means of rules. The approach has been tested in a hypertension application.

PMID- 15460763
TI  - CSCW--a paradigm for an efficient management of the healthcare organizations.
AB  - This paper reports the first results of the implementation of the research
      project CSCW--a paradigm for an efficient management of the healthcare
      organizations. The main objective of the project is to define a standard
      framework for the design of integrated systems for computer supported cooperative
      work applications in health management. The project is funded by the Romanian
      government and is carried on by an interdisciplinary team (researchers,
      educators, health professionals).

PMID- 15460764
TI  - Intelligent healthcare information assistant: towards agent-based healthcare
      knowledge management.
AB  - Initiatives in healthcare knowledge management have provided some interesting
      solutions for the implementation of large-scale information repositories vis-a
      vis the implementation of Healthcare Enterprise Memories (HEM). In this paper, we
      present an agent-based Intelligent Healthcare Information Assistant (IHIA) for
      dynamic information gathering, filtering and adaptation from a HEM comprising an
      amalgamation of (i) databases storing empirical knowledge, (ii) case-bases
      storing experiential knowledge, (iii) scenario-bases storing tacit knowledge and
      (iv) document-bases storing explicit knowledge. The featured work leverages
      intelligent agents and medical ontologies for autonomous HEM-wide navigation,
      approximate content matching, inter- and intra-repositories content correlation
      and information adaptation to meet the user's information request. We anticipate
      that the use of IHIA will empower healthcare stakeholders to actively communicate
      with an 'information/knowledge-rich' HEM and will be able to retrieve with ease
      'useful' task-specific information via the presentation of cognitively intuitive
      queries.

PMID- 15460765
TI  - Informal versus formal knowledge: IT development in health care.
AB  - Sustainable IT operation and maintenance through user participation in design and
      implementation of IT-systems in health care, is only secured if informal and
      formal knowledge are equally recognized. The paper argues that informal situated
      knowledge is of significance for the individual health care worker's performance.
      The concept indigenous knowledge is analyzed as a subset of informal knowledge
      and reference is made to the concepts of social capital and cultural capital.
      Finally, an approach rooted in Participatory Learning and Action methods is
      recommended as a technique for involving staff in IT-system design for
      technological change.

PMID- 15460766
TI  - Design considerations for an ontology in the domain of organ failure and
      transplantation.
AB  - The Etablissement francais des Greffes (EfG) is a national agency dealing with
      Public Health issues related to organ, tissue and cell transplantation in France.
      The evaluation of organ retrieval and transplantation activities, one of its
      missions, is supported by a national information system (IS). In order to
      facilitate data recording, to improve the quality of information and to prepare
      semantic interoperability with other information systems, the existing thesaurus
      of the EfG was audited, leading to the design a new terminological module devoted
      to the support of the domain ontology.

PMID- 15460767
TI  - Development of a computer controlled cognitive diagnostics and rehabilitation
      method.
AB  - In this paper we introduce a computer controlled method (HELp Neuropsychology =
      HELEN) which enables - as a difference to methods used internationally--not only
      the establishment of the diagnosis, but permits measurement of the effectiveness
      of the therapy. It allows: --To produce a database of the patients that contains
      not only their personal data but also the results of the tests, their drawings
      and audio recordings. --It is an intensive therapeutic test, which contains
      tutorial programs too.

PMID- 15460768
TI  - A preliminary study to assess a French code of ethics for health teaching
      resources on the Internet.
AB  - BACKGROUND: Constant assessment of the quality of health information on the
      Internet is an absolute necessity as peer review is often lacking in this media.
      OBJECTIVE: To develop a simple and easy French Code of Ethics, which will enable
      medical students to judge quality of health information in teaching material
      available on the Internet. DESIGN: Three medical informaticians selected ten
      criteria from previously established codes of ethics from Europe and the USA.
      This instrument was tested on a sample of 30 health Internet teaching resources.
      RESULTS: For the panel of experts, chance corrected inter-observer agreement
      (kappa) for quality rating ranged from k = -0.19 and k = 0.33, demonstrating poor
      agreement among the raters. CONCLUSION: If negative results of this preliminary
      study are confirmed by further research, this finding may detrimentally affect
      projects in Europe to accredit or certify Internet health resources.

PMID- 15460769
TI  - Software engineering in medical informatics: the academic hospital as learning
      environment.
AB  - In 2001, the revised course Software Engineering has been implemented in the
      Medical Informatics curriculum at the Academic Medical Center, Amsterdam. This 13
      weeks, full-time course consists of three parts: internship, theory and project.
      All parts are provided in problem-oriented manner with special attention for
      relevant skills such as project management, documentation and presentation.
      During the internship, students observe how health care professionals at several
      hospital wards work and how information supply is organized. In the theory part,
      students study concepts and methods of software engineering by means of case
      descriptions and self-directed learning. During the project, they apply their
      acquired knowledge to an observed, clinical information problem and complete
      several stages of the software engineering process. Evaluation by inquiry showed
      that, compared to other courses, students spent more time, and distributed their
      time more evenly, during the whole period of the course. In conjunction with
      theory, a combination of internship and project in a hospital seems to provide a
      surplus value compared to a practical in a computer laboratory. The integration
      of software theory, clinical practice and problem-based approach, contributed to
      the enthusiastic, intensive and realistic way students learned in this important
      topic that might be chosen as a future profession.

PMID- 15460770
TI  - Prevention of prescription errors by computerized, on-line, individual patient
      related surveillance of drug order entry.
AB  - Computerized prescription of drugs is expected to reduce the number of many
      preventable drug ordering errors. In the present study we evaluated the
      usefullness of a computerized drug order entry (CDOE) system in reducing
      prescription errors. A department of internal medicine using a comprehensive
      CDOE, which included also patient-related drug-laboratory, drug-disease and drug
      allergy on-line surveillance was compared to a similar department in which drug
      orders were handwritten. CDOE reduced prescription errors to 25-35%. The causes
      of errors remained similar, and most errors, on both departments, were associated
      with abnormal renal function and electrolyte balance. Residual errors remaining
      on the CDOE-using department were due to handwriting on the typed order, failure
      to feed patients' diseases, and system failures. The use of CDOE was associated
      with a significant reduction in mean hospital stay and in the number of changes
      performed in the prescription. The findings of this study both quantity the
      impact of comprehensive CDOE on prescription errors and delineate the causes for
      remaining errors.

PMID- 15460771
TI  - Methodological studies related to cardiovascular risk assessment.
AB  - Based on Framingham risk estimating equations by computer simulation graphical
      tools were gained allowing reasonable decision threshold adjustments in
      cardiovascular screening procedures. Results quantitatively characterize the
      percentage of the population selected for detailed evaluation vs. the decision
      threshold in a hypothetical screening procedure. In the second part of the study,
      the effect of blood pressure (BP) measurement uncertainties on coronary heart
      disease incidence estimates was characterized. According to our results the use
      of daily BP averages instead of instantaneous measurements has a significant
      impact on the risk estimation reliability.

PMID- 15460772
TI  - Which clinical decisions benefit from automation? A task complexity approach.
AB  - This paper describes a model for analysing medical decision making tasks and
      evaluation of their suitability for automation. The overall approach focuses on
      the assessment of decision complexity and possible reduction of human effort by
      automated decision support. The approach consists of five subsequent steps: (1)
      selection of the domain and relevant tasks; (2) evaluation of the knowledge
      complexity for tasks selected; (3) selection of potentially most cognitively
      demanding task; (4) assessment of unaided and aided effort requirements for this
      task accomplishment; and (5) selection of computational tools to achieve this
      complexity reduction. The model described allows for task automation without
      lowering of decision quality.

PMID- 15460773
TI  - Inter-participant agreement in the selection of symptoms for the description of
      seizures.
AB  - PURPOSE: To evaluate the inter-participant agreement in the selection of symptoms
      for the description of seizure types. METHODS: We evaluated the inter-participant
      agreement for a number of seizure types by comparing the actual agreement to the
      agreement that would result from random symptom selection as well as the maximal
      attainable agreement among participants that selected a different number of
      symptoms. RESULTS: For all seizure types the agreement in the symptom selection
      among the majority of the participants is significantly higher than expected by
      chance, but not reaching the maximum agreement attainable. CONCLUSION: Although
      the maximum agreement possible is not obtained, the symptoms selected by a
      majority of the participants seem to be adequate for the description of seizure
      types.

PMID- 15460774
TI  - Diabetes patients' ability to estimate dietary carbohydrate content for use in a
      decision support system.
AB  - The aim of the study was to assess Type 1 (insulin-dependent) diabetic patients'
      ability to give valid information of the dietary carbohydrate (CHO) intake and to
      use the log function of a blood glucose meter for easy transfer of data to a
      decision support system. 18 Type 1 diabetic patients were enrolled from the
      Diabetes Outpatient Clinic at the Department of Endocrinology, Aalborg Hospital,
      Denmark. The patients were divided in subgroups of 4 or 5 patients and was
      instructed by the dietitian how to estimate the CHO intake and by the doctor in
      the use of the Accutrend DM blood glucose meter. During a 3 days data collecting
      period the patients were asked to keep a written diary containing a description
      of the meals, the estimated CHO intake, the insulin-dosage and the time of the
      meals and insulin injections, and to make 8-point blood glucose profiles daily.
      They were furthermore asked to use the log function of the Accutrend DM blood
      glucose meter. At the second visit the data were discussed individually with the
      patients and if there where more than three data points missing using the log
      function the patients were asked to repeat the data collection. A deviation of 10
      grams or more, between the patient's and the dietician's estimate, was seen in
      7.3% of the meals following the first instruction, in 1.0% of the meals following
      the second instruction, and in 2.4% of the meals following the third and last
      instruction. In conclusion, this study showed that Danish Type 1 diabetic
      patients were able to estimate the dietary carbohydrate content with a high
      degree of correctness, and to use the log function of the blood glucose meter,
      after a maximum of 3 hours of training.

PMID- 15460775
TI  - Comparative analysis of cartilage structure on MR and CT images.
AB  - The magnetic resonance (MR) imaging device outperforms the quality of CT images
      for diagnosis related to soft tissues. The cartilage structure is intermediary
      between soft tissue and bones. The methodology to compare visualisation quality
      of two different CT and MR techniques was developed. It enabled to evaluate the
      equipment priority. Before carrying out the comparative analysis of cartilage
      structure images the method of reducing radiation dose for a CT examination has
      been developed. It was based on relationship between CT adjustment parameter
      (reconstruction increment) and image quality. The method enabled to carry out CT
      examination with a considerably reduced radiation dose for a patient and the
      medical personnel, taking part in the experiment.

PMID- 15460776
TI  - On prediction of hearing recovery after acute acoustic trauma caused by impulse
      noise.
AB  - The present study investigates the prediction of how successfully hearing returns
      to normal after an acute acoustic trauma caused by a firearm shot, an explosion
      or other impulse noise. Study material consisted of 113 conscripts who had
      suffered an acute acoustic trauma during their military service. A logistic
      regression model was formed to predict hearing recovery. From several possible
      variables at least five were found to be important among our dataset, which is
      still rather limited. However, more data will be acquired later in order to
      elaborate the research more widely by using other methods also.

PMID- 15460777
TI  - Managing resources in a GP national network: problems and achievements.
AB  - This paper presents the results and identifies problems in our experience
      concerning the development of Medinet sentinel dispensaries network in Romania.
      Medinet stations network consists in 100 computerized family doctors practices
      all around the country, where doctors collect primary care data and send it to
      the project central server through Internet. At present the network is fully
      functional and the collection of data have already started. Many problems have
      been identified while building and developing the network, both technical
      organizational and human resources problems.

PMID- 15460778
TI  - XML as standard for communicating in a document-based electronic patient record:
      a three years experiment.
AB  - During the past few years, the eXtensible Markup Language (XML) has experienced a
      growing use for accessing, representing and exchanging information, especially in
      the health care environment. This paper discusses the potentials of the use of
      XML for the electronic patient record (EPR) in two ways: first, as a format for
      the exchange of structured messages, and second, as a comprehensible way of
      representing patient documents. These statements rely on a three years experiment
      conducted at the Geneva University Hospital as part of its document-centred EPR.

PMID- 15460779
TI  - Discharge and referral data exchange using global standards--the SCIPHOX project
      in Germany.
AB  - The goal of the German project "Standardization of Communication between
      Information Systems in Physician Offices and Hospitals using XML" (aka SCIPHOX)
      is to provide an XML based information exchange between Hospital Information
      Systems (HIS) and Physician Office Systems (POS). HL7's Clinical Document
      Architecture (CDA) was chosen to serve as the "backbone" specification. The CDA
      is an ANSI approved document architecture for exchange of clinical information
      using XML. The SCIPHOX proposal specifies the use of the CDA in the context of
      discharge and referral letters in Germany, taking local needs (insurance
      information etc.) into account.

PMID- 15460780
TI  - The integration environment of the hospitals of H:S in Copenhagen.
AB  - This paper highlights the scenario implemented by the hospitals of the Copenhagen
      Hospital Corporation (H:S), for allowing the integration and interoperability of
      legacy and new systems, based on the establishing of a common and open
      information asset according to the CEN HISA standard and on top of the DHE
      middleware.

PMID- 15460781
TI  - A process for specifying integration for multi-tier applications in healthcare.
AB  - Integrating heterogeneous application systems in healthcare is needed to support
      clinical work, patient-centric care, regional interoperability and utilization of
      both valuable legacy systems and new technologies. The integration process is
      quite complicated, and must be supported by flexible integration processes and
      methods. The integration methods should support evaluation and specification of
      different integration approaches and technologies on many different
      interoperability levels. We introduce a process for specifying many integration
      decisions for a given integration situation. The process is part of an
      integration method, which is validated in PlugIT project in Finland.

PMID- 15460782
TI  - Integrating the lightweight authentication protocol (LAP) with access control
      mechanisms in wireless health care information systems.
AB  - Health information networks are expected to support information exchange that is
      authentic, accurate, private and available when, where and to whom is needed.
      With the increase of the shared medical information and resources in healthcare
      wireless information systems, unauthorized access to the information by illegal
      users also increases. The security of the transmitted information is a vital
      issue. In this paper, we report on the development of the Lightweight
      Authentication Protocol (LAP), which makes a mobile and distributed system more
      secure and flexible and we implement it in a Health Care Environment where the
      clinicians use mobile and wireless devices like PDAs. We also provide an
      indicative example of integrating the LAP with access control mechanisms. Context
      based Team Access Control (C-TMAC) model is used in this example, since it
      provides great flexibility on user-permissions management in collaborative
      healthcare environments. LAP is indeed capable to support efficiently the
      advanced authorization procedures of such demanding active security models.

PMID- 15460783
TI  - ICT penetration in public Greek hospitals.
AB  - Last year a survey was carried out with the main purpose to measure how ICT has
      been adopted in the public Greek hospitals. The survey was made possible in a
      rather short period of time through the utilisation of a questionnaire. H/W
      existence, application S/W installations, WWW sites and E-mail use as well as IT
      personnel employed, were among the factors that were studied. The outcomes of
      this survey present a rather high penetration in the administrative sector of the
      hospitals, whereas the medical sector faces a low level of computerisation. The
      absence in most of the hospitals, of a well-organised and appropriately staffed
      IT department, seems be one of the reasons for the low overall penetration of ICT
      in the average public Greek hospital.

PMID- 15460784
TI  - A web-based workflow system for emergency healthcare.
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. Workflow systems have recently received
      considerable attention in the healthcare field since they overcome organizational
      structures and support collaboration and coordination requirements by
      automatically routing relevant information where and when needed. In particular,
      healthcare workflow systems implemented over the Web can form the basis for a
      collaborative environment by bringing together healthcare professionals who are
      geographically dispersed and, hence, creating virtual healthcare workgroups
      organized around patient care. In this paper, a web-based workflow system is
      presented that was developed to support emergency healthcare processes and to
      provide an infrastructure for the integration of pre-hospital and in-hospital
      emergency healthcare.

PMID- 15460785
TI  - Health nets in Norway: national goals with regional actors.
AB  - The Norwegian national health net programme was established in 2001. Five
      regional health nets are the main building blocks in this net. The national
      health net provides an infrastructure and a set of basic services, and makes
      health information available for healthcare workers in primary care, hospitals
      and other health organisations. The national net does actually consist of five
      regional nets that is self-governed, and responsible for development and focus
      according to regional needs and priorities. The idea is to let local initiatives
      grow, and adopt the most successful initiatives nationally. This paper explains
      the approach, current status, near future and visions from a mid-Norwegian
      perspective.

PMID- 15460786
TI  - Building strategies for healthcare information systems.
AB  - An overview of the Romanian health information system development at a national
      scale is presented. A critical analysis of anterior phases tries to explain some
      of the differences between the expected results and real achievements. A set of
      principles for the "updated" strategy is proposed and each of them is associate a
      comment supporting its importance within the frame of present trends.

PMID- 15460787
TI  - Implementing regional information system for social and health care in Finland,
      Satakunta.
AB  - The Regional Information System, RIS is based on the open, regional architecture
      and it supports the regional, client-oriented seamless services in social and
      health care. By using the RIS it is possible for professionals for example to get
      an overview of the client's situation and to make a service chain plan for the
      client with the client's consent. The client can get access to his/her own data
      and to see his/her service plan, consents and log file. The development of the
      RIS started in the area of Satakunta in January 1999 and the implementation
      started in November 2001 in a national Macro Pilot project. The Ministry of
      Social Affairs and Health prepared a special law for Satakunta to enable the
      handling of client data in a regional context and the developing a regional
      system. The Ministry selected in the Spring 2001 three regions more in Finland to
      develop their services within the experimental Act. These four regions are
      approximately 50% out of the population in Finland.

PMID- 15460788
TI  - Information and logistics for homecare.
AB  - TELECOS is a regional project whose ambition is to use new cooperation tools, in
      the context of homecare, in order to facilitate the coordinated cooperative work
      of health actors. Homecare can improve the quality of life for the patient and
      reduce costs but it also induces a lot of difficulties during organisation and
      care. We aim at knowing more about the activity of cooperation in the homecare
      context and proposing a cooperation platform which answers to the specific needs
      generated during homecare and which integrates new applications. In this paper,
      we present the results of our study of homecare. The activity analysis leads us
      to determine two specific processes: one concerns the implementation of human and
      material resources and design of the homecare protocol (the logistics process)
      and the other concerns the coordination of the healthcare actors during effective
      homecare (the care process). The first process is composed of five main phases
      during which an healthcare professional is required as coordinator. We then
      present the Worklow model used to represent the cooperation activity in homecare.
      We describe the activity: the tasks and subtasks are represented in a declarative
      way. We then briefly present our prototype, devoted to homecare management,
      implementing the different phases of the information process, developed in JAVA.

PMID- 15460789
TI  - A distributed architecture for medical research.

PMID- 15460790
TI  - The impact of the introduction of Euro and other legislation changes on EU funded
      prototype for social and health care: the experience of EPIC in Savona.
AB  - We present the knowledge organisation of a database which aims to collect
      information for the optimisation of the social and heath care delivery in a
      limited territory within the guidelines set up by a EU funded project EPIC. The
      local implementation reflects the specificity of the social and health care
      delivery in the validation site: Savona. The paper discusses the features of the
      new rules which make compulsory an update of the first version of the software.

PMID- 15460791
TI  - Enhancing a medical e-learning environment: the adaptive DI2@DEM approach.
AB  - Current medical e-learning tools suffer from a variability of student user.
      Students are different in terms of motivations, training backgrounds, technical
      skills and learning objectives. It is obvious that these students do not accede
      relevant information if their educational resources access is misadapted.
      Adaptive environments propose to take the user into account in order to provide
      him or her with the most relevant educational resources. We present the adaptive
      DI(2)ADEM approach, which enhances the MEDIDACTE e-learning environment of the
      Faculty of Medicine in Marseille. DI(2)ADEM objective is to select the most
      relevant information and offer it to the user in an adaptive manner. Adaptability
      is based on management of knowledge regarding both the user and resources
      distributed. A match is made between student's profile and knowledge of resources
      organization and semantics.

PMID- 15460792
TI  - Virtual universities--the reality of e-learning?
AB  - With the growth of the internet and world wide web new ways of exchanging
      information are emerging, barriers are being overcome, new partnerships and ways
      of working are emerging. Amongst the hype is the notion of a Virtual University;
      it is hype or reality? What are the issues? A description of a University will
      not just include the programmes that it delivers but would no doubt include
      research and the academic environment. This paper raises some of the issues for
      Health Informatics.

PMID- 15460793
TI  - Training in health informatics in Brazil.
AB  - Developing countries, such as Brazil, are increasingly suffering from a severe
      shortage of health informatics specialists. Training of professionals in this
      field is expensive, and there is a limited supply of high-quality teaching
      resources available. We report on five initiatives of the Brazil/USA training
      program in health informatics. The main goal of this program is to train
      professionals in establishing medical informatics programs in Brazilian
      universities and major healthcare facilities.

PMID- 15460794
TI  - Telelearning in ophthalmology.
AB  - The virtual ophthalmic clinic has been developed to provide an interactive
      learning platform within the correspondence courses of the Virtual University of
      Bavaria. It presents clinical case examples from ophthalmology. Basic concepts
      are a case-based learning dialogue (didactics), peer reviewing (quality), role
      based access (organization) and thin web clients (availability). The following
      requirements had to be fulfilled: Best possible accessibility for students,
      authors and reviewers; learning control function; comfortable management. The
      application architecture is based on a relational data base, a ColdFusion
      (Allaire, Newton, MA, USA) web application server, a standard web server. So far,
      the application was used in four terms of the virtual university.

PMID- 15460795
TI  - New Czech Postgraduate Doctoral Program in Biomedical Informatics.
AB  - In the paper we describe the new Czech program in Biomedical informatics with
      doctor degree. The agreement on cooperation of Charles University in Prague and
      Academy of Sciences of the Czech Republic in postgraduate doctoral studies was
      signed on April 23rd, 1997. The main goal of this agreement has been cooperation
      in development and running of joint education and training of young researchers.
      Nowadays there are 19 boards of scientific disciplines in postgraduate doctoral
      studies in biomedicine, one of them the scientific board on Biomedical
      informatics established in 2001. The involvement of university teachers and
      researchers from the EuroMISE center-Cardio in the board of biomedical
      informatics discipline in the postgraduate doctoral studies of biomedicine and
      first activities of the board are described.

PMID- 15460796
TI  - Spatial analysis of rabies cases in foxes in Hungary between 1990 and 2001: a
      preliminary report.
AB  - In this paper we present the methodology and some preliminary results of the
      spatial analysis of rabies positive fox cases diagnosed in Hungary between 1990
      and 2001. A database has been built based on the data provided by the Animal
      Health and Food Control Department of the Ministry of Agriculture, of all
      registered positive cases, specifying the date, location and affected species. We
      have developed a Geographical Information System for the spatial analysis. The
      aim of the study is to analyse the spatial patterns of subsequent rabies cases.
      Beyond the well-documented seasonality of the cases we want to find out whether
      they show regular spatial patterns and if yes what is their nature. Another
      important question is whether clustering of data can be observed and how stable
      or reoccurring these clusters are at a given location or area. The results might
      be important in a later stage of the eradication campaign when a strategy for the
      maintenance of large, rabies free areas should be developed.

PMID- 15460797
TI  - Design of acquisition devices management subsystem for IEEE 1073 compliant
      software agents.
AB  - The paper addresses the issue of device management system design for software
      agents compliant with IEEE 1073 device communication standard. Based on
      middleware architecture the device control layer represents a universal versatile
      object-oriented application-programming interface. The approach presented in the
      paper allows to implement plug-and-play integration and interoperability of
      medical acquisition devices within the medical device system be means of common
      middleware services. Adherence to Medical Data Information Base nomenclature,
      component part of IEEE 1073 communication standard, adds necessary consistency to
      presented component-based infrastructure.

PMID- 15460798
TI  - Evaluation of medical informatics curriculum at the Rijeka University School of
      Medicine in Croatia.
AB  - This paper presents preliminary results from the study to evaluate the Medical
      Informatics curriculum at the Rijeka University School of Medicine, Rijeka,
      Croatia. Evaluation is based on the written anonymous. survey filled out by
      students after passing the exam. Questionnaire consisted of questions considering
      basic data (age, gender, study year, etc.), as well as students' opinions and
      marks on informatics, computer usage and teaching skills during the lessons. In
      total 459 students from five consecutive generations (from 1996/97 to 2000/01)
      were evaluated. Collected data define guidelines for teachers to improve
      organization and contents of curriculum. This study proved that, from one
      generation to the next, students show more and more interest in Medical
      Informatics, more of them have their own computer and more of them use Internet
      and e-mail communication.

PMID- 15460799
TI  - The simulation of emergency cases and other computer-based learning programs on
      the Internet for medical students and young doctors.
AB  - The aim of the project was to evaluate several of the most interesting Intemet
      "interactive patient" programs, as well as simulations of real clinical cases,
      and to compare them with a program "The Simulation of Emergency Cases" described
      in this work, and created by the Students' Research Group at the Department of
      Medical Informatics, the Medical University of Warsaw. These programs are aimed
      at medical students and doctors, and they are of great help in gaining medical
      experience in situations when the access to the real patient is limited.

PMID- 15460800
TI  - Electronic health center (eHC): integration of continuing medical education,
      information and communication for general practitioners.
AB  - The Electronic Health Center (eHC) is aimed as an Internet service for continuing
      medical education of general practitioners (GPs) at the national level. It
      integrates education, access to relevant and trusted information sources and
      group communication in order to meet the needs of both daily work and continuing
      education at home.

PMID- 15460801
TI  - DIACOM: a collective learning forum for continuing medical education.
AB  - DIACOM forum (Case based Interactive discussions for Medical education) is a
      computing tool dedicated to physicians in continuing education. Its goal is
      learning based on a distant clinical case confrontation between peers. Each
      learner can describe a case from his or her own experience, and the underlying
      system puts authors in touch whose cases have common points of interest. Research
      works managed in the SaSo Laboratory aims at developing a DIACOM from prototype
      for Continuing Medical Education (CME) in pediatric pain management. This paper
      presents the theoretical and pedagogic context and the functioning of the DIACOM
      forum.

PMID- 15460802
TI  - Using ICNP for nurse electronic charts and protocols in rehabilitation divisions.
AB  - The aim of this work is to promote the use of standard terminology for nursing
      documentation and for nurse protocols' description. We implemented an ICNP
      browser and we integrated it into two different systems: the nursing electronic
      patient record and the nursing protocols editor. The former allows nurses to
      choose ICNP terms for filling the clinical chart, while the latter allows
      computerising protocols using ICNP terms for the actions specification. Since, in
      a nursing information system, it should be worth to integrate protocols with the
      electronic patient record, sharing the same terminology is a crucial issue. We
      also show how we tailored the information system to the different wards. For each
      ward, we devised the most frequent patient needs and nursing actions. These lists
      are used to customise the different interfaces. Finally, by testing the prototype
      using real-world documents (clinical charts and protocols), we carried out an
      evaluation of the terminology itself, about its completeness and usability.

PMID- 15460803
TI  - A laboratory test request protocol system.
AB  - This paper describes the design, implementation and assessment of a computer
      based protocol application to support requests by clinicians for laboratory
      investigations. As part of the motivation for the work a rigorous engineering
      software approach was adopted not just for purely technical reasons but also as a
      means of maximising the role of the user.

PMID- 15460804
TI  - Medical information systems for cardiac risk assessment and remote monitoring.
AB  - Remote monitoring and interactive remote counselling provide a cost-effective and
      comfortable means of medical care. The paper presents the first experiences of
      two such systems, both in the field of cardiovascular diseases. The prototype
      medical instruments, the database design and the user interfaces are elaborated.
      The project runs until mid-2004.

PMID- 15460805
TI  - Collaboration--a new IT-service in the next generation of regional health care
      networks.
AB  - During the past 10-15 years, Regional Health Care Networks have been established
      in many regions throughout the world. Regional Health Care Networks build on well
      known techniques, methodologies and appropriate standards. Most of the European
      Countries have today set up IT strategic plans, with focus on establishment of
      Regional Health Care Networks. The benefits of having access to all relevant
      information are tremendous and provide a more cost-effective and coherent health
      service. By the rapid spread and use of Internet the technology have made it
      possible to interconnect all kinds of applications. The most experienced regions
      in Europe have joined a European project PICNIC to develop the Next Generation
      Regional Health Care Networks to support their new ways of providing health and
      social care. The previous generation of Regional Health Care Networks, developed
      in the past 10-15 years, supported the interconnection of applications by
      transfer of messages. This service will also continue to be one of the most
      important services in the future health care networks. Messaging is an effective
      means of integration of isolated high-specialised systems that only needs to
      exchange data. Tighter coupling may be desirable in some instances to avoid
      replicating the same functionality in several applications. In other words,
      certain services can be common and used by a number of applications instead of
      building that service inside each application. These common services are called
      middleware services. In PICNIC a new middleware Collaboration IT-service has been
      identified. This service allows the end users to perform real time clinical
      Collaboration, with exchange of text, structured data, voice and images.

PMID- 15460806
TI  - A framework for a diabetes mellitus disease management system in southern Israel.
AB  - Chronic diseases are a significant burden on western healthcare systems and
      national economies. It has been suggested that automated disease management for
      chronic disease, like diabetes mellitus (DM), improves the quality of care and
      reduces inappropriate utilization of diagnostic and therapeutic measures. We have
      designed a comprehensive DM Disease Management system for the Negev region in
      southern Israel. This system takes advantage of currently used clinical and
      administrative information systems. Algorithms for DM disease management have
      been created based on existing and accepted Israeli guidelines. All data fields
      and tables in the source information systems have been analyzed, and interfaces
      for periodic data loads from these systems have been specified. Based on this
      data, four subsets of decision support algorithms have been developed. The system
      generates alerts in these domains to multiple end users. We plan to use the
      products of this information system analysis and disease management specification
      in the actual development process of such a system shortly.

PMID- 15460807
TI  - Activity theory and medical informatics: usability, utility, and copability.
AB  - Working with health care today also means working with IT-systems. 'Human
      Factors' or 'user-friendly design' has been renowned as key factors for the
      development of safe and successful systems in many industries, not least in the
      IT-business. Likewise in the computerization of health care, the concepts of
      'usefulness' and 'usability' will become key issues in the daily life (and death)
      in health care context at hospitals, at the GP's office, and in the home of the
      patient. Though it is a pressing problem, the literature is still very scarce on
      how to meet this challenge. Inspired by activity theory, this paper sets out to
      coin a term for an important way to ask questions when determining the usefulness
      of a medical IT-system. We normally ask two types of questions: 'How usable is
      the system?' (usability), and 'How functional is the system?' (utility). But most
      important, we will also have to ask: 'How well does the user cope with the new
      situation?' As a concept for the latter way of asking questions, we will suggest
      the term 'copability'.

PMID- 15460808
TI  - Webmastering in academic institutions: a new job opportunity.
AB  - In cyberspace, the health webmaster could be regarded as a virtual editor-in
      chief, in charge of content and design. In this circumstance, he/she must follow
      quality criteria when building any resource. At the Rouen University Hospital
      (RUH), we have chosen "Net Scoring" as an effective tool to aid the design of a
      quality Web site. "Net Scoring" contains a list of 49 criteria which fall into
      eight categories: credibility, content, links, design, interactivity,
      quantitative aspects, ethics, and accessibility. The webmaster is the key element
      of the editorial board process. He/she must regularly monitor the Web site in
      order to retrieve information about whether the site is used and by whom: the
      method most commonly used is log analysis. At the RUH, an average of 9,000 unique
      machines visit our Web site each working day. Webmaster is a new job opportunity
      in academic institutions, in particular for medical informaticians and medical
      librarians both whom are information science professionals.

PMID- 15460809
TI  - Co-operative bidding of SMEs in health care sector.
AB  - Tendering become an important process for customers in the health care sector to
      select products and services from the market for the lowest price, with the
      highest quality and with the shortest delivery time. The number of SMEs (Small
      and Medium-sized Enterprises) delivering products or services for the health care
      sector is increasing, but they have usually limited capital and expertise to
      participate in tenders. The paper introduces a possible solution for this
      problem, when SMEs form special groups, so called Smart Bidding Organisations
      (SBO), to prepare a bid for the tender jointly. The SBO appears for the customer
      (tender issuer) as a single enterprise and the bidding procedure will be faster
      and less expensive in this way.

PMID- 15460810
TI  - Integrity, trust vs. opportunity.

PMID- 15460811
TI  - First, a true health care system.

PMID- 15460812
TI  - Other barriers to clinical IT.

PMID- 15460813
TI  - Legal obstacles to wiring docs.

PMID- 15460814
TI  - Management. The ratings game.

PMID- 15460815
TI  - Technology. Real world reality.

PMID- 15460816
TI  - Payment. Mega Medicaid cuts.

PMID- 15460817
TI  - Workforce. Crossing the U.S. border.

PMID- 15460818
TI  - Election preview. Split down the middle on health issues.

PMID- 15460819
TI  - Patient care. The waiting game.

PMID- 15460820
TI  - Management. A worthy bonus.

PMID- 15460821
TI  - Access and coverage. All for one.

PMID- 15460822
TI  - Dropping dead.
AB  - People continue to turn to hospitals for intervention and diagnostic services.
      But will hospitals always be the center of the health system?

PMID- 15460823
TI  - Chronic care: an acute problem.
AB  - Reality check: Nearly 80 percent of all health care dollars are now spent to
      treat chronic conditions. More than 100 million Americans suffer from one or more
      of these illnesses, a number that will swell in coming years. But health care-
      from the way it's paid for to the way it's delivere--remains heavily geared to
      acute care. Something's got to give.

PMID- 15460824
TI  - The rise and uncertain future of cath labs.
AB  - Few places have the potential to dramatically change the clinical and financial
      landscape."Cath labs are turning hospitals and health care upside down right now"
      says Skip Meador, director of cardiology for Centra Health, Lynchburg, Va."It's
      sure a different animal now than it was even seven or eight years ago"
      Cardiovascular programs--which increasingly rely on procedures performed in the
      cath lab--have long been the linchpin of hospital profitability, and have tended
      to prop up other money-losing areas. But critical issues threaten that
      profitability, such as the cost of technology, operating expenses and payer
      reimbursement. Likewise, such other technology as implantable cardiac
      defibrillators, biventricular pacemakers and ventricular assist devices bring
      more potential to change the landscape of cardiac care delivery. A case in point:
      the advent of primary angioplasty.

PMID- 15460825
TI  - The top ten malpractice claims [and how to minimize them].
AB  - Here are the 10 most common causes of malpractice lawsuits against hospitals and
      a range of potential solutions suggested by risk managers and patient safety
      experts.

PMID- 15460826
TI  - A guide to the safer use of dangerous medications. High-Alert medications.
AB  - Certain medications are designed "high alert' because they could cause serious
      harm if used incorrectly. Which are the high-alert meds and how can errors be
      averted?

PMID- 15460828
TI  - The American Hospital Quest for Quality Prize 2004. Sentara Norfolk (VA.) General
      Hospital Everyone's role is defined.

PMID- 15460829
TI  - The American Hospital Quest for Quality Prize 2004. Safety 'at the center of all
      things'. The Johns Hopkins Hospital, Baltimore.

PMID- 15460830
TI  - The American Hospital Quest for Quality Prize 2004. Preventing harm at any cost.
      Mary Lanning Memorial.

PMID- 15460831
TI  - Climbing mountains.
AB  - Economic stability and viability are an important part of doing business, but
      it's time health care leaders worried more about compassion and effective care.

PMID- 15460832
TI  - Ms. cardiovascular nurse, RN, MP.

PMID- 15460833
TI  - Hyponatremia and the nursing implications.
AB  - Serum sodium concentration plays a major role in the body's volume status. Low
      serum sodium levels can be dangerous and even fatal if hyponatremia is severe.
      The key to understanding hyponatremia is relating it to volume status.
      Hyponatremia is frequently associated with hypovolemia or fluid overload. Sharp
      assessment skills and client teaching can prove invaluable in the prevention and
      treatment of hyponatremia.

PMID- 15460834
TI  - What is the experience of men and women with congestive heart failure?
AB  - Congestive heart failure (CHF) is increasing in incidence and prevalence in both
      men and women in Canada. Research findings to date have been inconsistent with
      respect to whether gender differences influence quality of life, treatment and
      survival. There is a paucity of qualitative research describing the experience of
      patients with CHF This qualitative case study approach used semistructured
      interviews with women and men with New York Heart Association (NYHA) class three
      or four CHF who were referred to a CHF clinic. In addition to quality of life
      measures, data related to medical history, medical management and NYHA scores
      were collected to offer a thorough description of these clients' experiences.
      Three hypotheses were generated from 13 themes that emerged. First, the
      psychosocial impact of CHF outweighs the physical impact. Second, sex differences
      exist in relation to living with CHF with men being more accepting of CHF and
      more likely to experience social isolation and loss than women, while women are
      more likely to describe fear. Third, the experience of CHF is influenced by age
      with physical experiences and depression mentioned more frequently in younger age
      groups. Findings from this study have generated nursing implications and
      recommendations for further research.

PMID- 15460835
TI  - Biatrial myxoma: rare incidence in cardiac surgery.
AB  - A myxoma is a rare, usually noncancerous primary tumour of the heart. It is the
      most common benign cardiac tumour in adults, yet has a very low incidence in the
      cardiac surgery population, representing less than 1% of all cases. Biatrial
      myxomas are extremely rare, comprising only 2.5% of cardiac myxomas. Myxomas can
      be fatal due to embolic events or sudden death, however, prognosis after surgery
      is extremely good. The challenge for health care professionals is early
      recognition, diagnosis and treatment to prevent life-threatening events. This
      case presentation describes a gentleman with biatrial myxomas, and further
      discussion reviews the location, epidemiology, pathology, clinical presentation,
      assessment, diagnosis, and treatment aspects of cardiac myxomas. Since myxomas
      are a rare occurrence in cardiac surgery, it is hoped that this report may
      increase awareness and enhance cardiovascular nurses' understanding and knowledge
      in caring for the myxoma patient.

PMID- 15460836
TI  - Registered nurses' experiences with an evidence-based home care pathway for
      myocardial infarction clients.
AB  - OBJECTIVES: To obtain home health nurses' comments on an evidence-based care
      pathway for post myocardial infarction. DESIGN: A qualitative design was used.
      SETTING: Culturally diverse, lower income area of a large city. PARTICIPANTS: All
      home health nurses from one nursing agency who participated in a comparative
      study on the impact of the evidence-based care pathway. RESULTS: The largest
      number of comments made by the nurses were related to the beneficial impact of
      the pathway on the provision of quality nursing care and on increased job
      satisfaction. The home health nurses reported that the pathway increased clients'
      knowledge of medications and diet. In addition, they commented that they were
      able to use the pathway effectively because of the training they received from
      the inpatient cardiac nurses. CONCLUSIONS: This qualitative study demonstrates
      the benefits of investing in the implementation of best practice guidelines by
      home health nurses. However, nursing associations, such as the Canadian Community
      Health Nurses Initiatives Group, will need to continue to champion for additional
      funds to support the additional expenses incurred.

PMID- 15460837
TI  - Coronary artery bypass graft patients' pain perception during epicardial pacing
      wire removal.
AB  - Surgical placement of temporary epicardial pacing wires (EPWs) onto the
      epicardial surface of the heart is standard practice during cardiac surgery. The
      purpose of this study was to determine the intensity and quality of pain and
      sensations experienced during the procedure of EPWs removal for coronary artery
      bypass graft (CABG) patients. A descriptive study, incorporating the McGill Pain
      Questionnaire-short form and visual analogue scales, was used with 100 CABG
      patients requiring EPW removal. The pain intensity was reported as mild (47%),
      while the main sensation experienced was pulling (70%). Age, gender, previous
      cardiac surgery and EPW removal experience, and use of analgesics did not
      influence the pain and sensations experienced. However, subjects who had EPWs
      removed on post-operative day five or earlier did present with higher MPQ-SF
      affective and combined scores. CABG patients can be prepared for EPW removal by
      providing information that the procedure is a mildly painful, pulling sensation.

PMID- 15460838
TI  - Fostering research in nursing practice: clinical leadership in action.

PMID- 15460839
TI  - Combined multichannel intraluminal impedance and pH-metry: a novel technique to
      improve detection of gastro-oesophageal reflux literature review.
AB  - Ambulatory pH monitoring is currently the best method for detection of gastro
      oesophageal reflux. However, pH electrodes are able to measure only acid reflux,
      and therefore, non-acid reflux episodes, a potentially important cause of
      symptoms, are ignored by this technique. Multichannel intraluminal electrical
      impedance has recently been proposed as a novel method to overcome the above
      limitation of pH testing. Impedance (expressed in ohms) is a measure of the total
      opposition to current flow between adjacent electrodes. As refluxed contents are
      characterised by different conductivity, which is the inverse of impedance, for
      the first time a pH-independent accurate and practical qualitative analysis of
      refluxate is possible. For instance, the conductivity of air is almost zero and
      then impedance increases compared with baseline, whereas the conductivity of
      liquid is much higher and the impedance curve decreases remarkably. The
      combination of electrical impedance with traditional pH monitoring has the only
      aim of differentiating acid from non-acid liquid reflux. Moreover, the impedance
      catheter contains multiple pairs of ring electrodes along the oesophagus, so that
      an exact assessment of the proximal extent of refluxed material can be achieved.
      From a clinical point of view, electrical impedance + pH-metry could be useful
      for identifying the number and percent times of gas, acid and non-acid reflux
      episodes, to improve the yield of symptom index, to evaluate the reasons for poor
      response of reflux symptoms to proton pump inhibitors and to know the proximal
      extent of reflux events in patients with atypical symptoms. Thus, this technique
      has the potential to become a useful tool for improving our knowledge of gastro
      oesophageal reflux disease and optimising the management of these patients.

PMID- 15460840
TI  - Peptic ulcer--time trends at the turn of the millennium.

PMID- 15460841
TI  - Interferon-gamma and granulocyte colony-stimulating factor in bronchoalveolar
      lavage fluid after oesophagectomy.
AB  - BACKGROUND: Activated polymorphonuclear leucocytes play a pivotal role in
      pulmonary complications after oesophagectomy. A lot of inflammatory mediators
      including interferon-gamma and granulocyte colony-stimulating factor are reported
      to modify the life span of polymorphonuclear leucocytes. AIMS: In this study we
      investigated whether interferon-gamma and granulocyte colony-stimulating factor
      are associated with pulmonary complications after oesophagectomy. PATIENTS AND
      METHODS: We measured interferon-gamma and granulocyte colony-stimulating factor
      concentrations in bronchoalveolar lavage fluid of 37 patients who had undergone
      oesophagectomy and examined the relationship between these mediators and
      pulmonary complications. RESULTS: Pulmonary complications occurred in nine
      patients (24%, Pneum(+)). There was no significant difference in age, gender,
      preoperative comorbid conditions, tumour stage, operation method, operating time
      or blood loss between the Pneum(+) group and another 28 patients(Pneum(-)). Days
      until extubation were significantly increased in the Pneum(+) group than in the
      Pneum(-) group. Interferon-gamma (on postoperative day 2) and granulocyte colony
      stimulating factor (on postoperative days 1-3) in bronchoalveolar lavage fluid
      were significantly increased in the Pneum(+) group than in the Pneum(-) group and
      granulocyte colony-stimulating factor was significantly correlated with days
      until extubation. CONCLUSIONS: Our results indicate that bronchoalveolar lavage
      fluid granulocyte colony-stimulating factor is associated with respiratory
      conditions after oesophagectomy and assaying it can be useful for predicting
      pulmonary complications.

PMID- 15460842
TI  - Admission rates for peptic ulcer in the trent region, UK, 1972--2000. changing
      pattern, a changing disease?
AB  - BACKGROUND AND AIM: Peptic ulcer disease is believed to be less common and less
      severe as a result of modern medical treatment. We therefore examined changes in
      the admission rates for patients with duodenal ulcer and gastric ulcer, both
      emergency (for haemorrhage, perforation or severe pain) and for elective surgery,
      before and since the introduction of the new advances in therapy. These admission
      indices reflect disease prevalence and severity. PATIENTS AND METHODS: We
      identified admission rates during 1972--2000 within the Trent Regional Health
      Authority, UK (population 4.7 million), from computerised patient information
      using diagnostic search codes ICD8-10 and expressed as rates per million resident
      population. Drug expenditure details were obtained from the Department of Health.
      RESULTS: Emergency admission rates as a whole changed little, a decline in the
      young being offset by an increase in the elderly. Haemorrhage was the most common
      reason (approximately 115 per million for duodenal ulcer and 87 for gastric
      ulcer) throughout [compared with perforation (80 and 21) and pain (90 and 68)].
      In contrast, elective surgery has almost disappeared; this reduction began before
      the introduction of modern treatment. CONCLUSION: Emergency admission rates for
      duodenal and gastric ulcer for complications or severe pain have fluctuated over
      the last three decades but with little overall change. In contrast, elective
      surgery has declined dramatically, as a result of advances in treatment but also
      from changes in the natural history.

PMID- 15460843
TI  - Helicobacter pylori infection in Burkina Faso: an enigma within an enigma.
AB  - BACKGROUND: In Burkina Faso, in contrast with high rates of Helicobacter pylori
      infection from an early age, the prevalence of H. pylori-associated diseases
      (ulcer and gastric cancer) is low. AIMS: To look for the prevalence of H. pylori
      in healthy natives of Burkina Faso, both children and adults. METHODS: We studied
      the prevalence of H. pylori infection in 258 healthy natives of Burkina Faso (70
      children aged 6 months-15 years and 188 adults aged 16-65 years), using a
      serological screening (IgA and IgG H. pylori antibodies). All the studied
      subjects underwent a questionnaire regarding their life-style, socio-economic
      status, dietary habits and hygienic sanitary conditions. Data concerning the
      questionnaire were compared between H. pylori positive and negative subjects.
      RESULTS: The rates of H. pylori positivity in children were significantly higher
      than in adults, and in adults the positivity for H. pylori infection decreased
      with increasing age. The comparison of the questionnaire's data between H. pylori
      seropositive and seronegative subjects showed that poor socio-economic status and
      hygienic sanitary conditions were similar in the two groups. Instead, a higher
      prevalence of H. pylori positivity was observed in subjects belonging to families
      living in close contact with sheep, because of their labour and agro-pastoral
      tradition (shepherds and sedentary farmers). CONCLUSION: H. pylori infection in
      Burkina Faso is acquired early in life and is related not only to some yet well
      known risk factors (poor socio-economic and hygienic status), but also to a close
      contact with sheep. The gradually decreasing H. pylori seropositivity in adult
      population of Burkina Faso represents an unexplained enigma, which needs further
      studies.

PMID- 15460844
TI  - Different haemodynamic effects of a single dose of long-acting isosorbide-5
      mononitrate in healthy subjects and patients with cirrhotic portal hypertension.
AB  - BACKGROUND: The action pathways of nitrates are hypothesised to be deranged in
      cirrhosis. AIM: In order to confirm it, the acute haemodynamic effects of
      isosorbide-5-mononitrate in cirrhotic patients and controls was investigated.
      PATIENT: Nine cirrhotics and nine healthy controls. METHODS: Evaluation in the
      fasting state, 90 min after isosorbide-5-mononitrate or placebo (double-blind on
      two different days) and then 30 and 120 min after eating a standard meal. Various
      systemic and splanchnic haemodynamic parameters, including arterial impedance,
      assessed as Doppler pulsatility index, were measured. RESULTS: isosorbide-5
      mononitrate reduced arterial pressure and increased heart rate and mesenteric
      pulsatility index both in controls and in cirrhotics, whereas the following
      parameters behaved differently in the two groups (P < 0.05): hepatic pulsatility
      index decreased (-9%) and the portal velocity increased (+13%) in controls,
      whereas hepatic pulsatility increased (+18%) and portal velocity decreased (-18%)
      in cirrhotics. The two groups presented a similar pattern of changes in most
      variables under placebo after a meal. In controls, the administration of
      isosorbide-5-mononitrate blunted the postprandial mesenteric vasodilation and
      related changes in splanchnic and systemic circulation, expected at 30 min, in
      comparison to those observed under placebo. In cirrhotics, instead, the
      postprandial pattern was similar under placebo and isosorbide-5-mononitrate.
      CONCLUSIONS: The acute administration of isosorbide-5-mononitrate produces
      different haemodynamic effects in healthy and diseased livers, both in the
      fasting state and after a meal, consistent with the hypothesis of a deranged
      response of the intrahepatic microcirculation to nitrates in cirrhosis.

PMID- 15460845
TI  - A human umbilical cord stem cell rescue therapy in a murine model of toxic liver
      injury.
AB  - BACKGROUND: Several studies have demonstrated that bone marrow contains a
      subpopulation of stem cells capable of participating in the hepatic regenerative
      process, even if some reports indicate quite a low level of liver repopulation by
      human stem cells in the normal and transiently injured liver. AIMS: In order to
      overcome the low engraftment levels seen in previous models, we tried the direct
      intraperitoneal administration of human cord blood stem cells, using a model of
      hepatic damage induced by allyl alcohol in NOD/SCID mice. METHODS: We designed a
      protocol based on stem cell infusion following liver damage in the absence of
      irradiation. Flow cytometry, histology, immunohistochemistry and RT-PCR for human
      hepatic markers were performed to monitor human cell engraftment. RESULTS: Human
      stem cells were able to transdifferentiate into hepatocytes, to improve liver
      regeneration after damage and to reduce the mortality rate both in both
      protocols, even if with qualitative and quantitative differences in the
      transdifferentiation process. CONCLUSIONS: We demonstrated for the first time
      that the intraperitoneal administration of stem cells can guarantee a rapid liver
      engraftment. Moreover, the new protocol based on stem cell infusion following
      liver damage in the absence of irradiation may represent a step forward for the
      clinical application of stem cell transplantation.

PMID- 15460846
TI  - Imaging of primary sclerosing cholangitis: preliminary results by two new non
      invasive techniques.
AB  - BACKGROUND: Magnetic resonance cholangiography is a new technique which has
      already gained a role in primary sclerosing cholangitis. Computerised tomographic
      cholangiography is another non-invasive technique which has been used in
      assessing abnormal biliary tree, but has never been applied to evaluating primary
      sclerosing cholangitis. AIMS: To evaluate the ability of both magnetic resonance
      cholangiography and computerised tomographic cholangiography to detect bile duct
      changes in primary sclerosing cholangitis. PATIENTS AND METHODS: Magnetic
      resonance cholangiography and computerised tomographic cholangiography were
      performed in 16 primary sclerosing cholangitis patients. The computerised
      tomographic cholangiography data set was transferred to a processing workstation
      to obtain tridimensional reconstructions. Magnetic resonance cholangiography and
      computerised tomographic cholangiography images were analysed blind by two
      radiologists to assess: primary sclerosing cholangitis involvement, quality of
      imaging and the radiologist's certainty in determining the presence and location
      of the disease. RESULTS: Mean imaging quality was significantly better with
      computerised tomographic cholangiography compared with magnetic resonance
      cholangiography. Primary sclerosing cholangitis was identified in 15 cases with
      computerised tomographic cholangiography and 10 with magnetic resonance
      cholangiography (P < 0.05). Sensitivity in diagnosing primary sclerosing
      cholangitis was 94% with computerised tomographic cholangiography versus 63% with
      magnetic resonance cholangiography. Intrahepatic location was found in 14 cases,
      definitely present in 10 cases with computerised tomographic cholangiography and
      five with magnetic resonance cholangiography. Extrahepatic location was found in
      13 cases, definitely present in 11 cases with computerised tomographic
      cholangiography and four with magnetic resonance cholangiography (P < 0.05).
      Computerised tomographic cholangiography also offered dynamic information about
      biliary excretion. CONCLUSIONS: Computerised tomographic cholangiography enables
      more accurate detection and location of primary sclerosing cholangitis than
      magnetic resonance cholangiography. Since computerised tomographic
      cholangiography offers additional information about biliary excretion, it may be
      proposed as an integrative technique in the diagnosis and follow-up of patients
      with primary sclerosing cholangitis.

PMID- 15460847
TI  - Movement of a novel serum tumour marker, RCAS1, in patients with biliary
      diseases.
AB  - BACKGROUND: We have demonstrated immunohistochemically that RCAS 1 antigen is
      expressed in biliary neoplasms. Serum RCAS 1 levels are also elevated in a high
      percentage of patients with intra-hepatic cholangiocarcinoma. AIM: The study was
      designed to determine whether serum levels of RCAS1 are of clinical significance
      as a tumour marker for biliary tract tumour, in comparison to CA19-9. PATIENTS
      AND METHODS: In 38 patients with biliary carcinoma (gallbladder carcinoma, extra
      hepatic and intra-hepatic cholangiocarcinoma and ampullary carcinoma), we
      measured serum RCAS1 and CA19-9 levels. For control, serum samples from patients
      with benign biliary disease and healthy volunteers were also examined. RESULTS:
      We established a threshold value for RCAS1 of 17.5 U/ml, which permitted
      discrimination between malignant and non-malignant biliary diseases. In
      comparison to CA 19-9, serum RCAS1 was more sensitive and specific for
      malignancy, and was not influenced by cholestasis. RCAS1 levels varied with
      respect to the disease course and the effect of clinical treatment. CONCLUSIONS:
      Serum RCAS1 appears to be valuable as a diagnostic index for biliary carcinomas,
      as well as for evaluating the progression of cancers during therapy. We speculate
      that RCAS1 is a clinically more significant serum marker for biliary neoplasms
      than CA19-9.

PMID- 15460848
TI  - An unusual case of ascites.
AB  - A 76-year-old woman with abdominal pain and diarrhoea developed ascites that did
      not respond to treatment. There were no signs of liver damage. Abdominal
      ultrasonography with colour Doppler revealed an arterial-like flow in the
      enlarged splenic vein. Using selective mesenteric arteriography, we were able to
      diagnose a shunt between the inferior mesenteric artery and the inferior
      mesenteric vein. This is an unusual case of ascites due to prehepatic portal
      hypertension secondary to an extrahepatic arterioportal fistula.

PMID- 15460849
TI  - A life-threatening case of stenosing pill hypopharynx-oesophagitis caused by a
      tamsulosin capsule.
AB  - Pill oesophagitis is a frequent clinical entity that may induce dysphagia and
      exceptionally oesophageal occlusion. The mechanisms inducing mucosal inflammation
      are not completely defined, but oesophageal damage occurring when the caustic
      content of a drug remains in the oesophagus long enough to produce mucosal
      lesions seems to be a main factor. We report a case of a life-threatening
      stenosing pill hypopharynx-oesophagitis caused by the ingestion of a capsule of
      tamsulosin, a drug diffusely used for benign prostatic hyperplasia treatment.

PMID- 15460850
TI  - Pancreatic stenting for malignant ductal obstruction.
AB  - Pain is a major issue of palliative treatment in many patients with advanced
      pancreatic cancer. 'Obstructive'-type pain identified by correlation with meals,
      back radiation and dilation of main pancreatic duct upstream the stricture may be
      treated by endoscopic stent placement into the pancreatic duct in order to by
      pass the stricture. The clinical experience reported in the literature shows that
      pancreatic plastic stenting for 'obstructive' pain may provide complete relief of
      pain in about 60% of patients and partial relief in 25%.

PMID- 15460851
TI  - Acute pancreatitis due to simvastatin therapy: increased severity after
      rechallenge.

PMID- 15460852
TI  - Multiple pathogens found in growth-retarded black tiger shrimp Penaeus monodon
      cultivated in Thailand.
AB  - In 2001-2002 throughout Thailand, black tiger shrimp Penaeus monodon farmers
      reported very unusual retarded growth. We have called this problem monodon slow
      growth syndrome (MSGS). Based on decreased national production, estimated losses
      due to this phenomenon were in the range of 13 000 million baht (approximately
      300 million US dollars) in 2002. Since rearing practices had not changed, it was
      considered possible that the MSGS problem may have arisen from a new or existing
      pathogen. To examine this possibility, cultivated shrimp were sampled from 32
      commercial rearing ponds that reported abnormally slow growth from eastern,
      central and southern regions of Thailand. Shrimp were randomly sampled from each
      pond and grouped into normal and small shrimp. Normal shrimp were defined as
      those with body weights (BW) of 24 g or more while small shrimp were defined as
      those that weighed 16.8 g or less. Pleopods were used for detection of monodon
      baculovirus (MBV), heptopancreatic parvovirus (HPV) and infectious hypodermal and
      hematopoietic necrosis virus (IHHNV) using specific polymerase chain reaction
      (PCR) assays. In addition, some shrimp were processed for normal histopathology
      and transmission electron microscopy (TEM). Most of the shrimp specimens were
      infected by at least 1 of these viruses but many had dual or multiple infections.
      Prevalence of HPV and combined HPV/MBV infections in the small shrimp was
      significantly higher than in the normal shrimp. In addition to the viruses, a new
      microsporidian species, gregarines and bacteria were also observed but were not
      significantly associated with the MSGS problem. Some of the small shrimp gave
      negative results for all these pathogens by PCR and histology and no new and
      unique histopathology was recognized in any of the samples. The findings
      suggested that HPV infection was a contributing factor but not the overriding
      factor responsible for MSGS. It is possible that MSGS is caused by an unknown
      pathogen or by some other presently unknown, non-pathogenic factor.

PMID- 15460853
TI  - Infectivity of a Scottish isolate of Piscirickettsia salmonis for Atlantic salmon
      Salmo salar and immune response of salmon to this agent.
AB  - A Scottish isolate of Piscirickettsia salmonis (SCO-95A), previously shown by
      intraperitoneal injection to have a lethal dose (LD50) of < 2 x 10(3) infectious
      rickettsial units, was tested for virulence by bath challenge, surface
      application to the skin, or dorsal median sinus injection. Atlantic salmon Salmo
      salar post-smolts were used in all experiments, and exposure to 1 x 10(5) tissue
      culture infective doses (TCID) of P. salmonis ml(-1) for 1 h in a bath challenge
      resulted in only 1 mortality, 18 d later, in 10 exposed fish. Application of 2.5
      x 10(6) TCID of P. salmonis SCO-95A to paper discs on the skin failed to induce
      any mortalities within 42 d. Intraperitoneally, fish were administered vaccines
      containing 10(9) heat-inactivated (100 degrees C, 30 min) or 10(9) formalin
      inactivated P. salmonis SCO-95A in adjuvant, with a control group receiving
      phosphate-buffered saline (PBS) in adjuvant. After an induction period of over 6
      mo fish were challenged by injection of P. salmonis into the dorsal median sinus.
      Mortalities in the control group reached 81.8% and the heat-inactivated and
      formalin-inactivated vaccines gave significant protection from P. salmonis, with
      relative percentage survivals of 70.7 and 49.6%, respectively. The nature of the
      protective antigen is unknown, but could be lipopolysaccharide or a heat-stable
      outer membrane protein. Fish that survived a dorsal median sinus challenge of P.
      salmonis or were cohabitants showed a strong immune response to P. salmonis.

PMID- 15460854
TI  - Myxobolus cerebralis internal transcribed spacer 1 (ITS-1) sequences support
      recent spread of the parasite to North America and within Europe.
AB  - Molecular approaches for resolving relationships among the Myxozoa have relied
      mainly on small subunit (SSU) ribosomal DNA (rDNA) sequence analysis. This region
      of the gene is generally used for higher phylogenetic studies, and the
      conservative nature of this gene may make it inadequate for intraspecific
      comparisons. Previous intraspecific studies of Myxobolus cerebralis based on
      molecular analyses reported that the sequence of SSU rDNA and the internal
      transcribed spacer (ITS) were highly conserved in representatives of the parasite
      from North America and Europe. Considering that the ITS is usually a more
      variable region than the SSU, we reanalyzed available sequences on GenBank and
      obtained sequences from other M. cerebralis representatives from the states of
      California and West Virginia in the USA and from Germany and Russia. With the
      exception of 7 base pairs, most of the sequence designated as ITS-1 in GenBank
      was a highly conserved portion of the rDNA near the 3-prime end of the SSU
      region. Nonetheless, the additional ITS-1 sequences obtained from the available
      geographic representatives were well conserved. It is unlikely that we would have
      observed virtually identical ITS-1 sequences between European and American M.
      cerebralis samples had it spread naturally over time, particularly when compared
      to the variation seen between isolates of another myxozoan (Kudoa thyrsites) that
      has most likely spread naturally. These data further support the hypothesis that
      the current distribution of M. cerebralis in North America is a result of recent
      introductions followed by dispersal via anthropogenic means, largely through the
      stocking of infected trout for sport fishing.

PMID- 15460855
TI  - Evaluation of malacosporean life cycles through transmission studies.
AB  - Myxozoans, belonging to the recently described Class Malacosporea, parasitise
      freshwater bryozoans during at least part of their life cycle, but no complete
      malacosporean life cycle is known to date. One of the 2 described malacosporeans
      is Tetracapsuloides bryosalmonae, the causative agent of salmonid proliferative
      kidney disease. The other is Buddenbrockia plumatellae, so far only found in
      freshwater bryozoans. Our investigations evaluated malacosporean life cycles,
      focusing on transmission from fish to bryozoan and from bryozoan to bryozoan. We
      exposed bryozoans to possible infection from: stages of T. bryosalmonae in fish
      kidney and released in fish urine; spores of T. bryosalmonae that had developed
      in bryozoan hosts; and spores and sac stages of B. plumatellae that had developed
      in bryozoans. Infections were never observed by microscopic examination of post
      exposure, cultured bryozoans and none were detected by PCR after culture. Our
      consistent negative results are compelling: trials incorporated a broad range of
      parasite stages and potential hosts, and failure of transmission across trials
      cannot be ascribed to low spore concentrations or immature infective stages. The
      absence of evidence for bryozoan to bryozoan transmissions for both
      malacosporeans strongly indicates that such transmission is precluded in
      malacosporean life cycles. Overall, our results imply that there may be another
      malacosporean host which remains unidentified, although transmission from fish to
      bryozoans requires further investigation. However, the highly clonal life history
      of freshwater bryozoans is likely to allow both long-term persistence and spread
      of infection within bryozoan populations, precluding the requirement for regular
      transmission from an alternate host.

PMID- 15460856
TI  - Consumption of drugs for sea lice infestations in Norwegian fish farms: methods
      for assessment of treatment patterns and treatment rate.
AB  - Sea lice are a major problem in Norwegian fish farms; however, data on drug
      treatment patterns or treatment rates of sea lice infestations are not available.
      Such data are important for analysing resistance patterns against drugs used for
      such infestations. The main objective of the present study was to develop a
      method to estimate the treatment patterns and treatment rates for drugs used in
      the treatment against sea lice (Lepeophtheirus salmonis and Caligus elongatus) in
      farm salmonids by means of national sales statistics. Annual sales figures, as
      weight of active substances, were obtained from the drug wholesalers and the feed
      mills. The weight of active drug substances is not useful as a unit of
      measurement of drug use in an epidemiological context because it does not correct
      for dosage differences and number of repeat treatments. To correct for these
      factors, we introduced approved daily dose (ADD(farm fish)) and treatment course
      doses(farm fish) kg(-1) live-weight fish. To express the drug treatment patterns,
      the biomass (in weight) of farm salmonids treated with 1 course of a drug were
      estimated. When measured as kg active substance, the quantities of drugs for the
      treatment of sea lice infestations declined by 98% during the study period (1989
      to 2002) but this figure increased 5-fold when it was corrected for differences
      in dosage. To correct for amounts of farm salmonids liable to require treatment
      we estimated the annual treatment rate, defined as the number of treatments for
      sea lice infestations per biomass slaughtered Atlantic salmon Salmo salar and
      rainbow trout Oncorhynchus mykiss. The annual treatment rate increased gradually
      during the study period; however, it varied considerably (range 0.45 to 1.34,
      mean 0.90). Before 1995, organophosphates were the most frequently used drugs
      against sea lice; since then pyrethroids have become the dominating drug group.

PMID- 15460857
TI  - Influence of Anguillicola crassus (Nematoda) and Ichthyophthirius multifiliis
      (Ciliophora) on swimming activity of European eel Anguilla anguilla.
AB  - We investigated the swimming activity of 70 European eels Anguilla anguilla in
      relation to natural infection with 2 parasite species: the eel-specific
      swimbladder nematode Anguillicola crassus and the non-specific skin and gill
      protozoan Ichthyophthirius multifiliis. We measured how long individual eels
      exposed to a water current in a swimming channel with a steady-stream profile
      could withstand the water current. The parasites affected the swimming behaviour
      of eels in different ways. The maximum period of time the fish were able to swim
      against the current was not correlated with infection by A. crassus. In contrast,
      infection with I. multifiliis reduced the swimming time. The protozoan has a
      higher pathogenicity than the swimbladder nematode, at least in closed systems,
      where I. multifiliis is able to spread within a few days. Reduction in swimming
      capacity after infection with the ciliate averaged 47 % compared to capacity
      prior to infection. Thus, our results do not support the previously suggested
      strong negative relation between swimming activity of eels and intensity of A.
      crassus infection, at least in the short-term. However, there are indications in
      the literature that the pathological effects of A. crassus on the eel
      swimmbladder may involve a higher energy demand, possibly manifested in a
      prolonged spawning migration. As a result, eels heavily infected with this
      parasite may arrive too late at the spawning site to participate in mating. This
      could ensure a selection of 'good genes'.

PMID- 15460858
TI  - Rapid quantitative detection of chytridiomycosis (Batrachochytrium dendrobatidis)
      in amphibian samples using real-time Taqman PCR assay.
AB  - Batrachochytrium dendrobatidis is a major pathogen of frogs worldwide, associated
      with declines in amphibian populations. Diagnosis of chytridiomycosis to date has
      largely relied upon histological and immunohistochemical examination of toe
      clips. This technique is invasive and insensitive particularly at early stages of
      infection when treatment may be possible. We have developed a real-time PCR
      Taqman assay that can accurately detect and quantify one zoospore in a diagnostic
      sample. This assay will assist the early detection of B. dendrobatidis in both
      captive and wild populations, with a high degree of sensitivity and specificity,
      thus facilitating treatment and protection of endangered populations, monitoring
      of pristine environments and preventing further global spread via amphibian
      trade.

PMID- 15460859
TI  - Studies on the virulence of Aerococcus viridans (var.) homari, the causative
      agent of gaffkemia, a fatal disease of homarid lobsters.
AB  - Virulent and avirulent strains of Aerococcus viridans (var.) homari were used to
      extend previous studies to determine and confirm differences between the 2 types.
      Virulent strains possessed polysaccharide capsules and were not agglutinated by
      lobster hemolymph serum; avirulent strains did not have capsules, were
      agglutinated by the lobster hemolymph serum, and most did not grow well in
      lobster hemolymph serum. Growth of the avirulent strains in sterile lobster
      hemolymph serum induced the production of capsules (which reached a maximum after
      5 to 7 d incubation), eliminated susceptibility of the strains to the lobster
      serum agglutinin, and restored their virulence against lobsters. The factor(s) in
      lobster hemolymph serum inducing the long-lasting phenotypic response of
      virulence was (were) heat labile.

PMID- 15460860
TI  - Effect of nitrite on immune response of Taiwan abalone Haliotis diversicolor
      supertexta and its susceptibility to Vibrio parahaemolyticus.
AB  - Taiwan abalones Haliotis diversicolor supertexta held in 30% per thousand
      seawater and 26 degrees C were injected with tryptic soy broth (TSB)-grown
      Vibrioparahaemolyticus (1.6 x 10(5) CFU [colony-forming units] abalone(-1)), and
      then placed in water containing different concentrations of nitrite-N (nitrite as
      nitrogen): 0.01 mg l(-1) (control), 1.05, 3.04, 5.10 and 10.06 mg l(-1).
      Mortality of the abalones increased in direct parallel to ambient nitrite-N
      concentration. Over 12 to 48 h, the mortality of V. parahaemolyticus-injected
      abalones held in 3.04 mg l(-1) nitrite-N was significantly higher than that of
      abalones in the control solution. Abalones that had been exposed to control,
      0.96, 2.95, 5.03 and 10.16 mg l(-1) nitrite-N for 24, 72 and 120 h were examined
      for THC (total hemocyte count), phenoloxidase activity, respiratory bursts
      (release of superoxide anion), phagocytic activity, and clearance efficiency of
      V. parahaemolyticus. The THC increased in abalone after 72 h exposure to 0.96 and
      2.95 mg l(-1) nitrite-N, but decreased in abalones after 24 h exposure to 5.03
      and 10.16 mg l(-1) nitrite-N. Phenoloxidase activity and respiratory bursts
      increased, while phagocytic activity and clearance efficiency decreased in
      abalones exposed to > or = 0.96 mg l(-1) nitrite-N for 24 h. It is concluded that
      nitrite-N in water at concentrations as low as 0.96 mg l(-1) weakens the immune
      response and increases mortality of H. diversicolor supertexta infected with V.
      parahaemolyticus.

PMID- 15460861
TI  - Occurrence of Perkinsus sp. in undulated surf clams Paphia undulata from the Gulf
      of Thailand.
AB  - The undulated surf clam Paphia undulata supports Thailand's largest shellfishery
      in the Gulf of Thailand, with landings in 1999 recorded at 70000 t (metric
      tonnes) yr(-1). We report, for the first time, the prevalence of Perkinsus sp. in
      clams in the Gulf. A monthly survey from January to December 2001 utilizing the
      fluid thioglycollate medium (FTM) method showed that average monthly prevalence
      was 84.7% (n = 360). The monthly percentage of infected clams was generally 100%,
      with low prevalence in May (66.7%) and no infection in September. The monthly
      mean infection intensity in terms of Perkinsus sp. cells g(-1) tissue varied from
      0 in September to 187 759 +/- 18970 (x +/- SE) in October. No obvious annual
      variation in intensity and prevalence was observed. Prezoosporangia that
      developed in FTM were 25 to 75 pm in diameter. A few days after incubation in
      aerated seawater, the prezoosporangia underwent successive binary cell division
      and formed motile zoospores (2 to 5 microm long). The zoospores were released
      into the seawater through a discharge tube formed during the 2- and 4-cell
      stages. Serial semi-thin sections (1 to 4 pm thickness) of clam tissue (n = 120
      clams) showed developing trophozoites 3 to 6 pm in diameter within gills,
      connective tissue, gonads and, especially, the digestive glands. Microscopic
      features of different life stages indicated that Perkinsus sp. in Thailand
      closely resembled P. olseni (= P. atlanticus) reported in Australia, New Zealand,
      Korea, Japan, Spain and Portugal.

PMID- 15460862
TI  - Methods to enhance the intensity of intranuclear bacilliform virus infection in
      Cherax quadricarinatus.
AB  - Many studies have examined the morphology, pathology and epizootiology of the
      intranuclear bacilliform virus (IBV) of Cherax quadricarinatus, but little
      research has been conducted to acquire specific knowledge of the virus. This is
      partly due to difficulties in detecting the virus and in obtaining sufficient
      material for viral isolation and purification. As quantified by light microscopy,
      we significantly (p < 0.01) enhanced IBV intensities from 10.56 to 16.67% in C.
      quadricarinatus by using salinity stress (12 ppt) and ingestion of infected
      hepatopancreatic tissue, which increased intensities from 4.33 to 10.77%. It was
      also found that phosphotungstic acid-eosin stain was superior to standard
      haematoxylin and eosin stain in visualizing IBV inclusion bodies. It is expected
      that these new techniques will enhance the detectability of the virus and provide
      sufficient viral material for viral purification, characterization and
      development of molecular tools for detection and phylogenetic analysis.

PMID- 15460864
TI  - Chronic conditions ideas. Against the flow.

PMID- 15460863
TI  - National Ambulatory Medical Care Survey: 2002 summary.
AB  - OBJECTIVE: This report describes ambulatory care visits made to physician offices
      in the United States. Statistics are presented on selected characteristics of the
      physician's practice, the patient, and the visit. This report also highlights
      visits to primary care specialties. METHODS: The data presented in this report
      were collected from the 2002 National Ambulatory Medical Care Survey (NAMCS).
      NAMCS is a part of the ambulatory care component of the National Health Care
      Survey that measures health care utilization across various types of providers.
      NAMCS is a national probability sample survey of visits to office-based
      physicians in the United States. Sample data are weighted to produce annual
      national estimates. Selected trends from 1992, 1993, 1995, and 1997 are also
      presented. RESULTS: During 2002, an estimated 890 million visits were made to
      physician offices in the United States, an overall rate of 314.4 visits per 100
      persons. From 1992 through 2002, the visit rate for persons 45 years of age and
      over increased by 14%, from 407.3 to 465.8 visits per 100 persons. The visit rate
      to physician offices in metropolitan statistical areas (MSAs) (337.3 visits per
      100 persons) was significantly larger than the rate in non-MSAs (221.9 visits per
      100 persons). For one-half of all office visits, regardless of specialty,
      physicians indicated they were the patient's primary care physician (PCP). Of the
      visits to physicians other than the patient's PCP, about one-third (31.1 percent)
      were referrals. New patients, representing 12.1 percent of the visits in 2002,
      are down 18% since 1992. Primary care specialists provided 90 percent of all
      preventive care visits. Essential hypertension, acute upper respiratory
      infection, diabetes mellitus, and arthropathies were the leading illness-related
      primary diagnoses. There were an estimated 104.0 million injury-related visits in
      2002, or 36.7 visits per 100 persons. On average, 2.3 medications were ordered or
      provided at each office visit with any mention of a medication. The leading
      therapeutic class for drugs mentioned at office visits included nonsteroidal anti
      inflammatory drugs (NSAIDs) (4.9 mentions per 100 visits) and antidepressants
      (4.5 mentions per 100 visits). Of primary care specialists, 25.8 percent reported
      not accepting new patients who are Medicaid enrollees.

PMID- 15460866
TI  - Up front. Interview by Helen Mooney.

PMID- 15460867
TI  - Data briefing. Equality of access.

PMID- 15460868
TI  - Clinical management where medicine meets management. Fast forward.
AB  - Changes to doctors' training will leave trusts with gaps in service provision
      when they are introduced next year. The time junior doctors spend as senior house
      officers will be reduced from a minimum of three years to one. Critics are
      worried about the speed of implementation as well as the practicalities.

PMID- 15460869
TI  - Management trainees. Four for the future.

PMID- 15460870
TI  - Mental health. Best supporting act.

PMID- 15460871
TI  - High time for high impact. As the Modernisation Agency is scaled back this
      special supplement takes the chance to distil its 1,000 types of improvement into
      10 chapters that the organisation considers its legacy to the NHS.

PMID- 15460872
TI  - Absolute phase measurement in heterodyne detection of transient gratings.
AB  - We present a method of measuring the absolute phase in heterodyne-detected
      transient grating experiments. The method permits direct and sensitive
      characterization of the amplitude and phase of the grating parameters. We also
      present a convenient implementation of this technique and demonstrate its
      efficacy in a cuprate superconductor.

PMID- 15460873
TI  - Resonant directional coupling of hollow Bragg fibers.
AB  - Coupling between the lowest-loss TE01 modes of two touching hollow-core Bragg
      fibers is considered with a view to designing a directional coupler. We have
      found that for fibers with core radii larger than 10 microm one can identify
      broad frequency ranges in which intermodal coupling strength exceeds supermode
      radiation losses by an order of magnitude, thus opening the possibility of
      building a directional coupler. We attribute such unusually strong intermode
      coupling both to the resonant effects in the intermirror cavity and a proximity
      interaction between the leaky modes localized in the mirror.

PMID- 15460874
TI  - Fiber-optic extrinsic Fabry-Perot dc magnetic field sensor.
AB  - We demonstrate a compact extrinsic Fabry-Perot interferometer-based fiber-optic
      sensor that uses magnetostrictive amorphous metallic wire Unitika AF-10
      (Fe77.5B15Si7.5) as a sensor gauge for measuring dc magnetic fields. We present a
      theoretical model based on a Gaussian electric field distribution to analyze the
      sensor operation as a function of longitudinal air-gap separation. The model
      shows good agreement with the experimental results. A resolution of 50 nT over a
      range of 50-40,000 nT with a simple passive temperature-compensation method is
      obtained.

PMID- 15460875
TI  - Analytical solution of polarization mode dispersion for triangular spun fibers.
AB  - An analytical solution for the differential group delay of a fiber spun according
      to a triangular function is derived from concatenation of Jones matrices for a
      fiber length equal to N x T, where T is the spinning period and N is an integer.
      This solution holds for any value of linear deterministic birefringence delta
      beta of amplitude A and period T of the triangular spinning function. We use the
      solution to emphasize the effect of birefringence on the efficiency of the
      spinning function.

PMID- 15460876
TI  - Self-starting passive harmonic mode-locked femtosecond Yb3+-doped fiber laser at
      1030 nm.
AB  - We demonstrate, for the first time to our knowledge, a self-starting passive
      harmonic mode-locked femtosecond Yb3+-doped fiber laser with a scalable
      repetition rate of up to 585 MHz and >45 dB of supermode suppression. Pulse-to
      pulse jitter of approximately 14 ps is measured by optical cross correlation at
      the ninth harmonic, and radiofrequency (RF) spectrum measurements show that
      certain correlations exist between pulses in harmonic mode. Our results suggest
      that one of the proposed passive harmonic mode-locking mechanisms may be dominant
      for this laser.

PMID- 15460877
TI  - 200-m optical fiber with an integrated electrode and its poling.
AB  - More than 200 m of germanosilica optical fiber is manufactured with an internal
      wire electrode running parallel to the core. In this new fabrication method the
      wire is integrated into the fiber during the draw process. This length of fiber
      is an order of magnitude longer than other previously reported fibers with
      internal electrodes. The optical loss is less than our measurement floor of 0.5
      dB/m at 1550 nm. A 0.9-m section of the fiber is thermally poled, inducing a
      permanent second-order nonlinearity of 0.0125 pm/V. Methods to increase the
      induced nonlinearity are discussed. Integrating the wire into the fiber during
      the draw allows lengths of fiber with internal electrodes greater than 1 km to be
      manufactured and subsequently poled.

PMID- 15460878
TI  - Hydrogen loading for fiber grating writing with a femtosecond laser and a phase
      mask.
AB  - The threshold for the fabrication of fiber Bragg gratings with ultrafast 800-nm
      radiation and a phase mask was studied in SMF-28 and all-silica core fiber by use
      of 125-fs pulses. High-pressure molecular hydrogen loading (H2 loading) was
      observed to significantly lower the grating writing threshold in standard Ge
      doped telecommunication fiber. No reduction was observed with all-silica core
      fiber. The index change appeared to be confined to the Ge-doped core region of
      the fiber. Gratings in H2-loaded SMF-28 had thermal annealing behavior similar to
      UV-induced gratings. Unlike UV-induced H2-loaded gratings, no absorption
      associated with Ge-OH defect formation was observed.

PMID- 15460879
TI  - Chromatic confocal microscopy with a finite pinhole size.
AB  - Chromatic confocal microscopy has the advantage of short measurement times
      because of its parallel depth scan. As most white-light sources have limited
      optical output power, light-efficient setups are necessary. Using an extended
      detection pinhole is one way to improve light efficiency. We have calculated the
      effect of extended pinholes in chromatic confocal setups. We found that, for
      certain pinhole sizes, the FWHM of the confocal signal is nearly constant over a
      large wavelength interval.

PMID- 15460880
TI  - Enhancement of the cavity ringdown effect based on electromagnetically induced
      transparency.
AB  - We show that the unique absorption and dispersion properties of the
      electromagnetically induced transparency can be used effectively to relax the
      conditions for observing the cavity ringdown effect (CRE), which can be useful in
      applications of CRE in ultrasensitive detection of chemical species. A more
      straightforward and simple method is used to model the interesting CRE.

PMID- 15460881
TI  - Trapping cavitation bubbles with a self-focused laser beam.
AB  - We observed that laser-induced cavitation bubbles in water can be trapped in a
      self-focused laser beam. Both optical imaging and acoustic detection have been
      utilized to confirm bubble trapping. Transverse and longitudinal trapping forces
      were measured to be as large as 87 and 11 pN, respectively. This result is
      contrary to conventional wisdom, since the mechanism of trapping in conventional
      optical tweezers implies that a low-index particle (a bubble being the limiting
      case) should be antitrapped.

PMID- 15460882
TI  - Tracking optical coherence tomography.
AB  - An experimental tracking optical coherence tomography (OCT) system has been
      clinically tested. The prototype instrument uses a secondary sensing beam and
      steering mirrors to compensate for eye motion with a closed-loop bandwidth of 1
      kHz and tracking accuracy, to within less than the OCT beam diameter. The retinal
      tracker improved image registration accuracy to <1 transverse pixel (<60 microm).
      Composite OCT images averaged over multiple scans and visits show a sharp fine
      structure limited only by transverse pixel size. As the resolution of clinical
      OCT systems improves, the capability to reproducibly map complex structures in
      the living eye at high resolution will lead to improved understanding of disease
      processes and improved sensitivity and specificity of diagnostic procedures.

PMID- 15460883
TI  - Adaptive-optics ultrahigh-resolution optical coherence tomography.
AB  - Merging of ultrahigh-resolution optical coherence tomography (UHR OCT) and
      adaptive optics (AO), resulting in high axial (3 microm) and improved transverse
      resolution (5-10 microm) is demonstrated for the first time to our knowledge in
      in vivo retinal imaging. A compact (300 mm x 300 mm) closed-loop AO system, based
      on a real-time Hartmann-Shack wave-front sensor operating at 30 Hz and a 37
      actuator membrane deformable mirror, is interfaced to an UHR OCT system, based on
      a commercial OCT instrument, employing a compact Ti:sapphire laser with 130-nm
      bandwidth. Closed-loop correction of both ocular and system aberrations results
      in a residual uncorrected wave-front rms of 0.1 microm for a 3.68-mm pupil
      diameter. When this level of correction is achieved, OCT images are obtained
      under a static mirror configuration. By use of AO, an improvement of the
      transverse resolution of two to three times, compared with UHR OCT systems used
      so far, is obtained. A significant signal-to-noise ratio improvement of up to 9
      dB in corrected compared with uncorrected OCT tomograms is also achieved.

PMID- 15460884
TI  - Atom fiber for omnidirectional guiding of cold neutral atoms.
AB  - We present an omnidirectional matter waveguide on an atom chip. The guide is
      based on a combination of two current-carrying wires and a bias field pointing
      perpendicular to the chip surface. Thermal atoms are guided for more than two
      complete turns along a 25-mm-long spiral path (with curve radii as short as 200
      microm) at various atom-surface distances (35-450 microm). An extension of the
      scheme for the guiding of Bose-Einstein condensates is outlined.

PMID- 15460885
TI  - Simultaneously suppressing frequency and intensity noise in a Nd:YAG nonplanar
      ring oscillator by means of the current-lock technique.
AB  - We show that frequency and intensity noise in a Nd:YAG laser are correlated to a
      high degree and can be traced to the same underlying cause, namely, power
      fluctuations of the pump source. Because of this correlation, simultaneous
      suppression of frequency and intensity noise by 30 dB is achieved by means of a
      single actuator, the pump power.

PMID- 15460886
TI  - Suppression of polarization switching in vertical-cavity surface-emitting lasers
      by use of optical feedback.
AB  - The polarization properties of vertical-cavity surface-emitting lasers (VCSELs)
      subject to optical feedback are studied experimentally. It is thereby
      demonstrated that polarization-selective optical feedback can be utilized to
      entirely eliminate VCSEL polarization switching over the entire device operating
      range.

PMID- 15460887
TI  - 165-W cryogenically cooled Yb:YAG laser.
AB  - Thermo-optic distortions often limit the beam quality and power scaling of high
      average-power lasers. Cryogenically cooled Yb:YAG is used to efficiently generate
      165 W of near-diffraction-limited beam from a power oscillator with negligible
      thermo-optic effects. End pumped with 215 W of incident pump power from two diode
      modules, the laser has an optical-optical efficiency of 76%, a slope efficiency
      of 85%, and an M2 value of 1.02.

PMID- 15460888
TI  - Nanolayer parametric instability in near-field optics.
AB  - Parametric decay of electromagnetic waves into two Langmuir oscillations near the
      quarter critical density is suggested as being attributable to an enhanced
      electric field and to surface-enhanced Raman scattering in near-field optics. A
      nanolayer of silver aggregates localizes the wave in the evanescent region to a
      one-wavelength span and results in a wave-number mismatch as well as in a reduced
      growth rate. The fastest-growing mode has a growth rate that scales with the
      square root of the nanolayer's thickness.

PMID- 15460889
TI  - Carrier-wave Rabi flopping: role of the carrier-envelope phase.
AB  - Recently, a dependence of Rabi flopping on the carrier-envelope phase of the
      exciting laser pulses was predicted theoretically [Phys. Rev. Lett. 89, 127401
      (2002)] for excitation of a thin semiconductor film with intense few-cycle
      pulses. Here, we report corresponding experiments on 50-100-nm thin GaAs films
      excited with 5-fs pulses. We find a dependence on the carrier-envelope phase
      arising from the interference of sidebands from the fundamental or the third
      harmonic Mollow triplet, respectively, with surface second-harmonic generation.

PMID- 15460890
TI  - High-power supercontinuum generation in highly nonlinear, dispersion-shifted
      fibers by use of a continuous-wave Raman fiber laser.
AB  - High-power supercontinua are demonstrated in highly nonlinear, dispersion-shifted
      fibers with a continuous-wave Raman fiber laser. Supercontinuum growth is
      experimentally studied under different combinations of fiber length and launch
      power to show output powers as high as 3.2 W and bandwidths greater than 544 nm.
      Modulation instability (MI) is observed to seed spectral broadening at low launch
      powers, and the interplay between MI and stimulated Raman scattering plays an
      important role in the growth of the continuum at high launch powers. The effect
      on continuum generation of parametric four-wave mixing coupled with the higher
      order dispersion properties of the fiber is investigated.

PMID- 15460891
TI  - Narrowband tuning of an injection-seeded pulsed optical parametric oscillator
      based on a self-adaptive, phase-conjugate cavity mirror.
AB  - Narrowband tuning of a pulsed optical parametric oscillator (OPO) is achieved
      with a self-adaptive injection-seeded optical cavity employing a phase-conjugate
      reflector. This approach is used in a novel OPO system based on periodically
      poled KTiOPO4 and pumped at 532 nm by a pulsed Nd:YAG laser. The OPO is injection
      seeded at 835-855 nm by a continuous-wave tunable diode laser, which also enables
      a Rh:BaTiO3 photorefractive crystal to act as a wavelength-selective phase
      conjugate reflector, with no need for active control of cavity length. The single
      longitudinal-mode tunability and operational simplicity of this OPO system are
      demonstrated experimentally.

PMID- 15460892
TI  - Compact efficient all-solid-state eye-safe laser with self-frequency Raman
      conversion in a Nd:YVO4 crystal.
AB  - An efficient compact eye-safe laser at 1525 nm is presented by use of self
      frequency Raman conversion in a diode-pumped actively Q-switched Nd:YVO4 1342-nm
      laser. At an incident pump power of 13.5 W, the self-stimulated Raman laser
      produces 1.2 W of 1525-nm average output power at a repetition rate of 20 kHz.
      The corresponding peak power at 1525 nm is generally greater than 10 kW for
      repetition rates from 5 to 20 kHz.

PMID- 15460893
TI  - Observation of surface states in a truncated photonic crystal slab.
AB  - The effect of lattice termination on the surface states in a two-dimensional
      truncated photonic crystal slab is experimentally studied in a high-index
      contrast silicon-on-insulator system. A single-mode silicon strip waveguide that
      is separated from the photonic crystal by a trench of variable width is used to
      evanescently couple to surface states in the surrounding lattice. It is
      demonstrated that the dispersion of the surface states depends strongly on the
      specific termination of the lattice.

PMID- 15460894
TI  - Resonant infrared transmission through SiC films.
AB  - Resonant transmission through metallic films is observed when a periodic array of
      holes is drilled. This phenomenon has been attributed to surface plasmon
      polaritons. We study a similar system made of an array of slits in a SiC film
      supporting surface phonon polaritons. We find a resonant transmission in the
      infrared. The role of surface waves is analyzed. We find that surface waves are
      excited at resonance but are not a necessary condition to obtain a resonant
      transmission.

PMID- 15460895
TI  - Wavelength-dependent optical force on elliptical silver cylinders at plasmon
      resonance.
AB  - We use rigorous diffraction theory to analyze the force on elliptical cylinders
      made from silver as a function of the elongation. We find that, when the wires
      are illuminated at the plasmon wavelength and placed in a highly focused Gaussian
      beam, they are attracted toward the optical axis if the waist of the laser is
      behind the wire and repelled if the waist is before the wire. Also, the force
      distributions of illumination wavelengths smaller and larger than the plasmon
      wavelength are analyzed.

PMID- 15460896
TI  - High-efficiency, simple setup for pulse cleaning at the millijoule level by
      nonlinear induced birefringence.
AB  - Nonlinear elliptical polarization rotation is used to improve the contrast of
      femtosecond pulses by several orders of magnitude. Using nonlinear induced
      birefringence in air, we produced cleaned pulses with an energy of a few hundreds
      of microjoules. This technique presents several major advantages, such as
      convenience and stability of the setup. We investigated the phase profile
      required for obtaining high-energy pulses. No phase distortion is observed, and
      the spatial quality of the beam is preserved.

PMID- 15460897
TI  - Femtosecond shaping of transverse and longitudinal light polarization.
AB  - Femtosecond laser pulse shaping techniques have been restricted to propagating
      transverse electromagnetic waves. We present a scheme for pulse shaping of
      optical near fields based on the excitation of longitudinal electromagnetic
      fields with polarization-shaped light pulses. By solving Maxwell's equations for
      a model nanostructure, i.e., a scanning tunneling microscope tip, with help from
      the boundary-element method, we demonstrate that the electric field vector
      oscillates in a complex yet controllable fashion in three dimensions. Many
      applications are envisioned because literally another dimension in the optimal
      control of light-matter interaction is accessible.

PMID- 15460898
TI  - Biophysic evaluation of bone quality-application of Fourier transform infrared
      spectroscopy and phosphorus-31 solid-state nuclear magnetic resonance
      spectroscopy.
AB  - In this review, we focus on findings obtained with biophysic techniques, Fourier
      transformed infrared (FTIR) spectroscopy and phosphorus-31 solid-state nuclear
      magnetic resonance (31P solid-state NMR) spectroscopy, which may allow us to
      evaluate bone quality and to predict bone strength. FTIR measures the absorption
      energy that produces an increase in the vibrational or rotational energy of atoms
      or groups of atoms within the molecule. FTIR spectroscopy allows us to examine
      the relative amount of minerals and matrix content and the arrangement of apatite
      and organic matrix. FTIR spectroscopy should become an important tool, because
      the relative amount of minerals and the arrangement of apatite and organic matrix
      could be a measure for evaluating bone quality. 31P solid-state NMR spectroscopy
      is useful for evaluating the quality of bone and predicting bone strength by
      calculating the spine-lattice relaxation time (T1) of bone. 31P solid-state NMR
      imaging can be used to measure quantitatively the mass of hydroxyapatite. The T1
      relaxation time of both bone and deficient hydroxyapatite was much longer than
      that of pure hydroxyapatite. T1 relaxation time is one of the promising indices
      of bone quality.

PMID- 15460899
TI  - Stress control and human nutrition.
AB  - Stress is a pervasive factor in everyday life that critically affects development
      and functioning. Severe and prolonged stress exposure impairs homeostatic
      mechanisms, particularly associated with the onset of depressive illness. Brain
      food is aimed at preventing as well as treating a growing number of stress
      related mental disorders. Some topics on the association of stress and nutrition
      is reviewed. (1) An increased activity of serotonergic neurons in the brain is an
      established consequence of stress. An increase in brain tryptophan levels on the
      order of that produced by eating a carbohydrate-rich/protein-poor meal causes
      parallel increases in the amounts of serotonin released into synapses. (2) Eating
      is thought to be suppressed during stress, due to anorectic effects of
      corticotrophin releasing hormone, and increased during recovery from stress, due
      to appetite stimulating effects of residual cortisol. (3) A strong inverse
      association between coffee intake and risk of suicide. (4) Night eating syndrome
      has been found to occur during periods of stress and is associated with poor
      results at attempts to lose weight and disturbances in the hypothalamic-pituitary
      adrenal axis. (5) Dietary antioxidants present in fruits and vegetables may
      improve cognitive function. Therefore, it is concluded that the establishment of
      functional foods that correctly regulate stress response must be firmly based
      upon scientific knowledge and legal regulation.

PMID- 15460900
TI  - The p16INK4a-RB pathway: molecular link between cellular senescence and tumor
      suppression.
AB  - The p16INK4a tumor suppressor protein functions as an inhibitor of CDK4 and CDK6,
      the D-type cyclin-dependent kinases that initiate the phosphorylation of the
      retinoblastoma tumor suppressor protein, RB. Thus, p16INK4a has the capacity to
      arrest cells in the G1-phase of the cell cycle and its probable physiological
      role is in the implementation of irreversible growth arrest termed cellular
      senescence. Cellular senescence is a state of permanent growth arrest that can be
      induced by a variety of stresses such as DNA-damage and aberrant mitogenic
      signaling in human primary cells. In contrast to normal cells, the function of
      the p16INK4a gene or its downstream mediators is frequently deregulated in many
      types of human cancers, illustrating the importance of cellular senescence in
      tumor suppression. Here we discuss the molecular mechanisms that direct cellular
      senescence and reveal its potential for tumor suppression.

PMID- 15460901
TI  - Recommendations to develop an intervention for Japanese youth on weight
      management.
AB  - In the last 20 years the average change in BMI among Japanese youth is minimal,
      but significant changes appear when the categories of overweight/obesity and
      underweight are investigated within gender. Now intervention programs for
      Japanese youth on weight management need to be developed. To address the issue,
      there are a series of steps that could be undertaken utilizing theory of behavior
      change. Using the Transtheoretical Model-Stages of Change as the health promotion
      theory an intervention could be developed that would tailor messages to the level
      of the stage of readiness to weight change that exists among youth. Different
      aspects of the intervention could be developed and targeted to groups of youth by
      their needs. To assist with planning and development of the intervention
      principles of Intervention Mapping could be used to guide development using data
      from a needs assessment survey to: a) determine youths' knowledge, attitudes and
      beliefs about body size, b) determine youth's barriers to change in body size, c)
      determine parental knowledge, attitudes and beliefs about body size, d) determine
      parental barriers to change in youth body size, e) determine the prevalence of
      health problems from low and high BMI of young females and males, f) determine
      which youth are at risk-rural/urban areas, socioeconomic status.

PMID- 15460902
TI  - Three-dimensional imaging of thoracic diseases with multi-detector row CT.
AB  - The benefits of multi-detector row CT (MDCT) relative to single-detector row
      helical CT are considerable. Multi-detector row CT allows shorter acquisition
      times, greater coverage, and superior image resolution. These factors
      substantially increase the diagnostic accuracy of the examination. Three
      dimensional (3D) volume data from MDCT provides various unique applications on
      thoracic diseases. These includes isotropic viewings, use of multiplanar
      reformation (MPR), maximum and minimum intensity projections (MIP and minIP), and
      volume rendering performed from external and internal perspectives allowing the
      user to "fly around" and "fly through" the structures. Recent advances in 3D
      volume rendering put real-time, interactive virtual reality guidance of the
      procedures such as bronchoscopy and surgery into practice.

PMID- 15460903
TI  - Nutritional factors, parasite infection and allergy in rural and suburban
      Vietnamese school children.
AB  - Urban areas often have more allergy than rural areas. Dietary patterns and
      parasite infection have been suggested as possible related factors. This study
      evaluated the prevalence of allergy in school children in one rural and suburban
      area of Vietnam where parasite infection is common. A total of 195 children aged
      9 to 13 years old completed a self-administered allergy questionnaire and
      provided blood and stool samples for analysis. Nutritional status, dietary intake
      and parasite infection were determined in all participants. Allergy was more
      common in girls (10.7% vs. 7.6%), suburban children (11.8% vs. 6.9%), children
      with weight-for-age (16.7% vs. 6.0%) and height-for-age (14.8% vs. 4.9%) in the
      10th to 75th percentile compared to <3rd percentile, and in children without
      trichuriasis compared to light trichuriasis (12.5% vs. 9.3%), although none of
      these comparisons were statistically significant. Logistic regression adjusted
      for sex, age and area of residence revealed no association between allergy and
      nutritional status, food intake or parasite infection. Intake of riboflavin,
      however, was negatively associated with allergy (OR=0.00, 95% CI:0.00-0.65,
      p=0.038). In conclusion, we were unable to detect any association between allergy
      and nutritional status, diet, or parasite infection. However, in a population
      with high undernutrition and parasite infection, the prevalence of allergy was
      low and the extremely low intake of riboflavin was associated with a higher risk
      of allergy.

PMID- 15460904
TI  - Donor-specific tolerance induced by simultaneous allogeneic islet transplantation
      with CD4+CD25+ T-cells into hepatic parenchyma in mice.
AB  - BACKGROUND: The allogeneic islets transplantation is an ideal therapeutic
      strategy for patients with diabetes mellitus. However, it has been difficult to
      induce immunological tolerance against islets grafts. The CD4+CD25+ regulatory T
      cells (Treg) play a role in suppressing T-cell activation. Thus, we evaluated
      whether Treg can regulate donor-specific T-cell tolerance that received
      allogeneic islets into the hepatic parenchyma (ITxHP) along with Treg. METHODS:
      C3H/He mice were used as donors; and streptozotocin-induced diabetic BALB/c mice
      were recipients. The protocol included three groups: Group A recipients received
      only 300 IE islets; Group B was given 300 IE islets and whole splenocytes; Group
      C was given 300 IE islets and Treg purified from peripheral lymph nodes. RESULTS:
      For all mice in Groups A and B, the fasting blood sugar exceeded 250mg/dl and
      graft rejection was observed. GVHD was observed earlier in Group B than in Group
      A. In contrast graft survival exceeded 30 days for two mice in Group C (50%, mean
      POD 28.5 +/- 24.0, P<0.05). Mixed lymphocyte reaction showed that T-cells from
      tolerant mice had very weak responses against spleen cells from C3H mice.
      CONCLUSIONS: The simultaneous ITxHP with CD4+CD25+ T-cells administration
      prolonged islet graft survivals and induced donor-specific hyporesponsiveness.

PMID- 15460905
TI  - The effect of continuous arterial infusion of gabexate mesilate (FOY-007) on
      experimental acute pancreatitis.
AB  - The effectiveness of continuous arterial infusion of Gabexate Mesilate (FOY-007)
      on experimental acute pancreatitis was investigated. Acute necrotizing
      pancreatitis was induced by an injection of 10% Na-taurocholate (1ml/kg) into the
      main pancreatic duct of mongrel dogs. Animals were divided into three groups;
      Group A: non-treated control, Group B: after the induction of pancreatitis,
      injected with FOY-007 intravenously (5mg/kg/hr), Group C: after the induction of
      pancreatitis, injected with FOY-007 via the celiac artery. The changes in the
      values of amylase and lipase in serum and ascites etc. were examined. A
      histological examination was done and the FOY-007 concentration of the pancreas
      was measured. In both groups B and C, the serum levels of amylase and lipase
      reached significantly to low levels compared with those in group A. The extents
      of pancreatic parenchyma necrosis in each group were 36.1, 25.3 and 19.5%,
      respectively, and were significantly improved in group C. In addition, the FOY
      007 levels in pancreas specimens in the intraarterial infusion group exceeded
      those in the intravenous infusion group by 32 times. The results suggest that
      continuous FOY-007 arterial infusion therapy is useful as a local treatment for
      severe acute pancreatitis.

PMID- 15460906
TI  - Reduction of expression of the multidrug resistance protein (MRP)1 in glioma
      cells by antisense phosphorothioate oligonucleotides.
AB  - The tumor cells' acquisition of resistance to multiple drugs due to
      overexpression of the multidrug resistance protein (MPRP)1 gene is one of major
      obstacles in cancer chemotherapy. We have attempted to reverse the multidrug
      resistance (MDR) phenotype by treating etoposide resistant glioma cell lines
      (T98G-VP and Gli36-VP) with RP1 antisense oligonucleotides. 20-mer
      phosphorothioate oligodeoxynucleotide (0.3 microM), complementary to the coding
      region in the MRP cDNA sequence, could significantly inhibit the growth of
      multidrug resistant cell lines, T98G-VP and Gli36-VP, cultured in etoposide
      containing medium. No such effect was observed for the parental T98G and Gli36
      cell lines. Further investigations by the reverse transcription-polymerase chain
      reaction and immunoblotting revealed that antisense oligomer could result in a
      reduction in the level of MRP1 mRNA, probably through hindering MRP1 gene
      transcription. This study demonstrates that the antisense oligonucleotides can
      increase the sensitivity of the tumor cells to the anticancer drug by decreasing
      the expression of the MRP gene. This strategy may be applicable to cure cancer
      patients with MRP mediated MDR phenotype.

PMID- 15460907
TI  - Correlation of vascular endothelial cell proliferation with microvessel density
      and expression of vascular endothelial growth factor and basic fibroblast growth
      factor in hepatocellular carcinoma.
AB  - Tumor-associated angiogenesis is essential for tumor growth or metastasis, and
      consists of multiple and sequential steps regulated by proangiogenic and
      antiangiogenic factors. Vascular endothelial cell proliferation is involved in
      this process. We investigated the correlation of vascular endothelial cell
      proliferation with microvessel density (MVD) and expression of major
      proangiogenic molecules, vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF) in hepatocellular carcinoma (HCC). Formalin-fixed
      paraffin-embedded specimens of surgically resected HCC from 67 patients were
      used. Proliferating endothelial cells were detected by immunofluorescence double
      staining for CD34 and proliferating cell nuclear antigen (PCNA). The
      proliferation activity of endothelial cells was determined by the rate of PCNA
      positive endothelial cells, and evaluated at the periphery and center of the
      tumors and adjacent non-neoplastic livers. MVD and the expression of VEGF and
      bFGF in the tumors were also examined immunohistochemically. The proliferation
      activity of endothelial cells at the periphery of the tumors was significantly
      higher than that at the center of the tumors (35.8% vs. 12.7%, P<0.0001). The
      rate of PCNA-positive endothelial cells in the tumors with higher bFGF expression
      was significantly higher than that in the tumors with lower bFGF expression
      (44.8% vs. 32.5%, P<0.005) at the periphery of the tumors. There was no
      significant correlation between the rate of PCNA-positive endothelial cells and
      clinicopathological findings or MVD. In HCC, the proliferation activity of
      vascular endothelial cells is suggested to be heterogeneous in the tumor and
      higher at the periphery of the tumor, and bFGF may play an important role in the
      positive regulation of tumor-associated vascular endothelial cell proliferation.

PMID- 15460908
TI  - Direct lymphatic spreading route into the liver from the gallbladder: an animal
      experiment using pig.
AB  - In the special occasion that the physiological lymphatic flow is obstructed,
      gallbladder carcinoma (GBC) may spread into the liver via lymphatic route.
      Therefore, this study was conducted to find out the direct lymphatic route
      draining into the liver from the gallbladder using pigs with ligated cystic
      ducts. After injecting the carbon particle suspension (CH40) or the contrast
      medium (Lipiodol) into the subserosal layer of the gallbladder, the lymphatic
      route into the liver was examined both macroscopically and histologically. In
      controls, CH40 or Lipiodol drained along the cystic duct toward the
      hepatoduodenal ligament. After occlusion of cystic duct, CH40 was interrupted at
      the ligated point, and then spread into the liver nearby the gallbladder bed,
      running off to the liver hilus, toward the hepatoduodenal ligament. This route
      was confirmed by the Lipiodol drainage into the right median lobe of the liver,
      equivalent to the segments V and IV a in humans. We presented for the first time
      the emergence of lymphatic drainage from the gallbladder into the liver after the
      occlusion of physiological lymphatic route using pigs. This implies that the
      direct spread into the segments V and IV a of liver should be considered in the
      surgical treatment of advanced GBC.

PMID- 15460909
TI  - Basic study of new diagnostic modality according to non-invasive measurement of
      the electrical conductivity of tissues.
AB  - The purposes of this study were to estimate the electrical conductivity of
      tissues by non-invasively measuring the electrical bio-impedance, to develop a
      new method for tissue diagnosis, i.e., electrical impedance tomography (EIT).
      Tissue models were first designed taking into consideration the distribution of
      the fat tissue, muscle and bone in the human forearm, and then the intra-tissue
      distributions of electrical potential and field, and the electrical impedance in
      the models was theoretically analyzed by the three-dimensional finite element
      method. The electrical impedance of both forearms was measured in healthy human
      subjects, and estimated the electrical conductivity of individual local tissues.
      The results of the analysis showed that the distributions of electrical potential
      and field were affected by the presence of fat tissue but not by the presence or
      absence of bone. In addition, as a result of calculation of the electrical
      resistance of the extracellular fluid (Re) in each model, it was found that the
      value of bio-impedance was influenced by the presence of fat tissue, and the
      value of bio-impedance was increased by the intervention of a fat layer. The
      electrical conductivity estimated by fitting the observed values to the values
      obtained by finite element analysis was 0.40 S/m and 0.15 S/m for male muscle and
      fat tissue, and 0.35 S/m and 0.11 S/m for female muscle and fat tissue,
      respectively. The sex difference in the slope of linear approximation in the
      estimation of electrical conductivity of the males and females was thought to be
      due to sex differences in the properties and structure of fat tissue. These
      results suggest that local tissues can be diagnosed differentially and
      electrically by percutaneous measurement of local bio-impedance and subsequent
      estimation of the electrical conductivity of each tissue.

PMID- 15460910
TI  - The relationship between standard uptake value (SUV) and Hounsfield Unit (HU) of
      oral contrast agent for FDG-PET/CT study.
AB  - The aim of this study was to examine the relationship between CT density
      (Hounsfield Unit, HU) and the degree of fluoro-deoxyglucose (FDG) uptake,
      demonstrated as standard uptake value (SUV). Twenty contiguous patients (9 males,
      11 females, age range of 29-79) were performed FDG-PET/CT scan with 750ml of 5%
      iodine-based oral contrast agent. A region of interest (ROI) was placed manually
      on oral contrast in the lumen of stomach, small bowel and ascending colon,
      avoiding contamination of other structures, and the average SUV and average HU
      were determined. R square and p value were applied to evaluate the correlation.
      The correlation between SUV and HU in each separate location is not significant.
      When all regions are combined, p value is significant (<0.05), but R square is
      not significant. Oral contrast can be one factor that influences measured FDG,
      and it is possible it acts as an irritant that increases metabolism in the bowel
      wall, resulting in increased FDG uptake.

PMID- 15460911
TI  - Eye care project in Gaur, Nepal.
AB  - PURPOSE: The aim of the eye care project is to clear the backlog of cataract
      blindness for the people of Gaur and its surrounding districts in southeast
      Nepal. The purpose of this study is to analyze the progress of this eye care
      project. METHODS: In mid 1997, the Nepal Netra Jyoti Sangh (NNJS), the national
      society for comprehensive eye care in Nepal, with financial support from the
      Association for Ophthalmic Cooperation to Asia (AOCA) and the 24 Hour Television
      (24HTV) Charity Committee established an eye hospital in the district
      headquarters of Gaur under the name of Narayani Eye Care Project (NECP). The
      hospital provides surgery, an outpatient department (OPD) and emergency services.
      We analyzed the number of patients, the number of surgeries and the profile of
      patients. RESULTS: The hospital was found to be providing services with modern
      equipment and instruments and the number of patients frequenting it had increased
      in accordance with the improved services. From mid 1997 until the end of 2002,
      the hospital provided services to a total of 122,093 patients and performed 6,143
      major surgeries and 541 minor surgeries. CONCLUSIONS: It has been possible to
      conduct sight restorations of poor and blind individuals in this region at the
      Gaur eye hospital with the support of the NECP.

PMID- 15460912
TI  - A case of early-stage lung cancer detected by autofluorescence bronchoscopy.
AB  - A 71-year-old man was referred to our hospital for further examination of
      abnormal sputum cytology. No abnormal nodular shadows were detected in chest X
      ray and chest CT. The location of the tumor was clearly identified as a defect of
      autofluorescence by autofluorescence bronchoscopy at the bifurcation between the
      left B1+2 and B3 bronchi, whereas it was quite difficult by conventional
      bronchoscopy. Transbronchial biopsy revealed squamous cell carcinoma. Further
      examinations yielded the diagnosis of early-stage lung cancer. Photodynamic
      therapy was performed and complete response was confirmed. This case indicates
      the efficacy of autofluorescence bronchoscopy for detecting early-stage lung
      cancer.

PMID- 15460913
TI  - Forensic casework of personal identification using a mixture of body fluids from
      more than one person by Y-STRs analysis.
AB  - We applied Y-STRs (DYS385/DYS19/YCAII) to an adhesive plaster left at a crime
      scene. This plaster may have included body fluids from more than one person.
      Firstly, we performed preliminary examinations, ABO-blood type examinations, and
      commonly used DNA examinations (D1S80, HLADQalpha, TH01, and PM) on these
      specimens. As a result of these examinations, we could evidence that suspect A
      did not contacted with the plaster, but could not confirm the presence of
      perspiration from suspect B. As the next step, we applied Y-STR examination to
      the plaster. Using this examination, we detected alleles that coincided to those
      of suspect B. We also concluded that the fluid from an unidentified person was
      vaginal fluid based on crime scene investigation. Y-STRs examination data
      obtained from 124 persons in Tokushima prefecture showed that 1.613% of
      individuals demonstrated haplotypes 10-18/15/19-23, which was detected from the
      plaster and from suspect B. Therefore, we considered that there was a high
      probability that the persiration detected in the plaster was that of suspect B.
      Based on these studies, we concluded that Y-STR examination of trace evidence was
      very useful to screen suspects using materials that contained body fluid from
      more than one person.

PMID- 15460914
TI  - Application of AmpFISTR Profiler PCR Amplification kit for personal
      identification of a putrefied cadaver.
AB  - A putrefied cadaver of a middle-aged woman was found drifting in the 'Kii" water
      course. Autopsy findings indicated that the postmortem duration was about one
      week, and the cause of death was assumed to be drowning. In this case, a nail was
      collected as a sample for personal identification. After five months of police
      investigation, persons thought to be her family, husband and child, were found. A
      combination of D1S80 and the short tandem repeat (STR) typing system using an
      AmpFISTR Profiler PCR Amplification kit was performed for identification. Nine
      STRs (D3S1358, vWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317 and D7S820) and
      Amelogenin were analyzed by this kit. Those DNA typings successfully confirmed
      the family relation for personal identification of the cadaver. This analysis
      system may be useful for identification of a decomposed cadaver.

PMID- 15460915
TI  - A patient with sustained ventricular tachycardia: identification of a responder
      to amiodarone using signal-averaged electrocardiogram.
AB  - A 75-year-old man suffered sustained ventricular tachycardia with syncopal
      attack. Ventricular tachycardias appeared repeatedly, and an electrical
      defibrillator was used after an anti-arrhythmic drug, such as lidocaine or
      mexiletine, proved ineffective. The tachycardias had multiple origins, and the
      signal-averaged electrocardiogram (SAECG) showed ventricular late potential
      before the administration of amiodarone. After administration, the filtered QRS
      and duration of the late potential increased, but the recurrence of tachycardias
      was suppressed. The reason for this is thought to be that amiodarone blocked the
      sodium channel and delayed conduction, consequently blocking reentry, because
      amiodaron has antiarrhymic properties with a prolongation of refractoriness and
      minimal effect on conduction velocity in ventricular myocardium, and inhibits
      sympathetic activity, and blocks L-type calcium channel besides the depression of
      the fast sodium channel. In this case, SAECG predicted to some degree whether or
      not this patient's ventricular tachycardia would respond to amiodarone.

PMID- 15460916
TI  - Nursing and its future status.

PMID- 15460917
TI  - An HIV/AIDS issue in nursing practice.

PMID- 15460919
TI  - Brighter noise: sensory enhancement of perceived loudness by concurrent visual
      stimulation.
AB  - Two experiments investigated the effect of concurrently presented light on the
      perceived loudness of a low-level burst of white noise. The results suggest two
      points. First, white noise presented with light tends to be rated as louder than
      noise presented alone. Second, the enhancement in loudness judgments is resistant
      to two experimental manipulations: varying the probability that light accompanies
      sound and shifting from a rating method to a forced choice comparison. Both
      manipulations were previously shown to eliminate a complementary noise-induced
      enhancement in ratings of brightness. Whereas noise-induced enhancement of
      brightness seems to reflect a late-stage decisional process, such as a response
      bias, the present results suggest that light-induced enhancement of loudness may
      reflect an early-stage sensory interaction.

PMID- 15460920
TI  - Do small white balls squeak? Pitch-object correspondences in young children.
AB  - Adults with auditory-visual synesthesia agree that higher pitched sounds induce
      smaller, brighter visual percepts. We have hypothesized that these
      correspondences are remnants of cross-modal neural connections that are present
      at birth and that influence the development of perception and language even in
      adults and children without synesthesia. In this study, we explored these
      correspondences in preschoolers (30-36 months; n = 12 per experiment). The
      children were asked to indicate which of two bouncing balls was making a
      centrally located sound. The balls varied in size and/or surface darkness; the
      sound varied in pitch. The children reliably matched the higher pitched sound to
      a smaller and lighter (white) ball (Experiment 1), to a lighter (white) ball
      (Experiment 2), and in one of two groups, to a smaller ball (Experiment 3).
      Children's matching of pitch and size cannot be attributed to intensity matching
      or to learning. These data support the hypothesis that some cross-modal
      correspondences may be remnants of the neural mechanisms underlying neonatal
      perception.

PMID- 15460918
TI  - Long-distance feedback projections to area V1: implications for multisensory
      integration, spatial awareness, and visual consciousness.
AB  - It is generally agreed that information flow through the cortex is constrained by
      a hierarchical architecture. Recent experimental evidence suggests that
      projections descending the hierarchy and targeting the primary visual cortex
      (area V1) may play an essential role in perceptual processes. We have, therefore,
      reexamined feedback projections to area V1, using retrograde tracer injections in
      this area In addition to well-known areas, quantification of labeling in higher
      cortical areas reveals a number of hitherto unknown long-distance feedback
      connections originating from auditory (A1), multisensory (STP) cortices, but also
      from a perirhinal area (36). These feedback projections from advanced cortical
      stations, a global feature shared by areas that belong to the ventral visual
      stream, could play an important role in early multisensory integration and
      spatial awareness and could provide the physical substrate for the involvement of
      area V1 in visual consciousness.

PMID- 15460921
TI  - Infants' perception of rhythm and tempo in unimodal and multimodal stimulation: a
      developmental test of the intersensory redundancy hypothesis.
AB  - Research has demonstrated that young infants can detect a change in the tempo and
      the rhythm of an event when they experience the event bimodally (audiovisually),
      but not when they experience it unimodally (acoustically or visually). According
      to Bahrick and Lickliter (2000, 2002), intersensory redundancy available in
      bimodal, but not in unimodal, stimulation directs attention to the amodal
      properties of events in early development. Later in development, as infants
      become more experienced perceivers, attention becomes more flexible and can be
      directed toward amodal properties in unimodal and bimodal stimulation. The
      present study tested this developmental hypothesis by assessing the ability of
      older, more perceptually experienced infants to discriminate the tempo or rhythm
      of an event, using procedures identical to those in prior studies. The results
      indicated that older infants can detect a change in the rhythm and the tempo of
      an event following both bimodal (audiovisual) and unimodal (visual) stimulation.
      These results provide further support for the intersensory redundancy hypothesis
      and are consistent with a pattern of increasing specificity in perceptual
      development.

PMID- 15460922
TI  - Spatial constraints on visual-tactile cross-modal distractor congruency effects.
AB  - Across three experiments, participants made speeded elevation discrimination
      responses to vibrotactile targets presented to the thumb (held in a lower
      position) or the index finger (upper position) of either hand, while
      simultaneously trying to ignore visual distractors presented independently from
      either the same or a different elevation. Performance on the vibrotactile
      elevation discrimination task was slower and less accurate when the visual
      distractor was incongruent with the elevation of the vibrotactile target (e.g., a
      lower light during the presentation of an upper vibrotactile target to the index
      finger) than when they were congruent, showing that people cannot completely
      ignore vision when selectively attending to vibrotactile information. We
      investigated the attentional, temporal, and spatial modulation of these cross
      modal congruency effects by manipulating the direction of endogenous tactile
      spatial attention, the stimulus onset asynchrony between target and distractor,
      and the spatial separation between the vibrotactile target, any visual
      distractors, and the participant's two hands within and across hemifields. Our
      results provide new insights into the spatiotemporal modulation of cross-modal
      congruency effects and highlight the utility of this paradigm for investigating
      the contributions of visual, tactile, and proprioceptive inputs to the
      multisensory representation of peripersonal space.

PMID- 15460923
TI  - Mislocalizations of touch to a fake hand.
AB  - Observers can mislocalize a tactile target delivered to an unseen hand if a
      visible rubber glove is positioned next to a pair of distractor lights that flash
      in correlation with the tactile target (Pavani, Spence, & Driver, 2000). In the
      present study, we explored visual, tactile, and postural factors that influence
      this fake hand effect. Comparison with baseline conditions revealed that the fake
      hand effect was larger than a general spatial congruity effect but weaker than
      the effect obtained when tactile and visual stimuli were actually in the same
      locations (Experiment 1). Surprisingly, the effect did not depend on direct
      vision of the fake hand (Experiments 1 and 2), nor was it enhanced by congruent
      tactile information (Experiment 3). However, the fake hand effect was sensitive
      to the postural compatibility of the real and the fake hands (Experiment 4).
      These findings indicate that the available sensory information is used flexibly
      to incorporate the rubber glove into the body schema.

PMID- 15460924
TI  - Vision of a pictorial hand modulates visual-tactile interactions.
AB  - The participants in this study discriminated the position of tactile target
      stimuli presented at the tip or the base of the forefinger of one of the
      participants' hands, while ignoring visual distractor stimuli. The visual
      distractor stimuli were presented from two circles on a display aligned with the
      tactile targets in Experiment 1 or orthogonal to them in Experiment 2. Tactile
      discrimination performance was slower and less accurate when the visual
      distractor stimuli were presented from incongruent locations relative to the
      tactile target stimuli (e.g., tactile target at the base of the finger with top
      visual distractor) highlighting a cross-modal congruency effect. We examined
      whether the presence and orientation of a simple line drawing of a hand, which
      was superimposed on the visual distractor stimuli, would modulate the cross-modal
      congruency effects. When the tactile targets and the visual distractors were
      spatially aligned, the modulatory effects of the hand picture were small
      (Experiment 1). However, when they were spatially misaligned, the effects were
      much larger, and the direction of the cross-modal congruency effects changed in
      accordance with the orientation of the picture of the hand, as if the hand
      picture corresponded to the participants' own stimulated hand (Experiment 2). The
      results suggest that the two-dimensional picture of a hand can modulate processes
      maintaining our internal body representation. We also observed that the cross
      modal congruency effects were influenced by the postures of the stimulated and
      the responding hands. These results reveal the complex nature of spatial
      interactions among vision, touch, and proprioception.

PMID- 15460925
TI  - When mirrors lie: "visual capture" of arm position impairs reaching performance.
AB  - If we stand at a mirror's edge, we can see one half of our body reflected in the
      mirror, as if it were the other half of our body, seen "through" the mirror. We
      used this mirror illusion to examine the effect of conflicts between visually and
      proprioceptively specified arm positions on subsequent reaching movements made
      with the unseen right arm. When participants viewed their static left arm in the
      mirror (i.e., as if it were their right arm), subsequent right-arm reaching
      movements were affected significantly more when there was conflict between the
      apparent visual and the proprioceptively specified right-arm positions than when
      there was no conflict. This result demonstrates that visual capture of arm
      position can occur when individual body parts are viewed in the mirror and that
      this capture has a measurable effect on subsequent reaching movements made with
      an unseen arm. The result has implications for how the brain represents the body
      across different sensory modalities.

PMID- 15460926
TI  - Perceiving object motion using vision and touch.
AB  - In a previous experiment, we showed that bistable visual object motion was
      partially disambiguated by tactile input. Here, we investigated this effect
      further by employing a more potent visuotactile stimulus. Monocular viewing of a
      tangible wire-frame sphere (TS) rotating about its vertical axis produced
      bistable alternations of direction. Touching the TS biased simultaneous and
      subsequent visual perception of motion. Both of these biases were in the
      direction of the tactile stimulation and, therefore, constituted facilitation or
      priming, as opposed to interference or adaptation. Although touching the TS
      biased visual perception, tactile stimulation was not able to override the
      ambiguous visual percept. This led to periods of sensory conflict, during which
      visual and tactile motion percepts were incongruent. Visual and tactile inputs
      can sometimes be fused to form a coherent percept of object motion but, when they
      are in extreme conflict, can also remain independent.

PMID- 15460927
TI  - Congruency effects between auditory and tactile motion: extending the phenomenon
      of cross-modal dynamic capture.
AB  - Behavioral studies of multisensory integration in motion perception have focused
      on the particular case of visual and auditory signals. Here, we addressed a new
      case: audition and touch. In Experiment 1, we tested the effects of an apparent
      motion stream presented in an irrelevant modality (audition or touch) on the
      perception of apparent motion streams in the other modality (touch or audition,
      respectively). We found significant congruency effects (lower performance when
      the direction of motion in the irrelevant modality was incongruent with the
      direction of the target) for the two possible modality combinations. This
      congruency effect was asymmetrical, with tactile motion distractors having a
      stronger influence on auditory motion perception than vice versa In Experiment 2,
      we used auditory motion targets and tactile motion distractors while participants
      adopted one of two possible postures: arms uncrossed or arms crossed. The effects
      of tactile motion on auditory motion judgments were replicated in the arms
      uncrossed posture, but they dissipated in the arms-crossed posture. The
      implications of these results are discussed in light of current findings
      regarding the representation of tactile and auditory space.

PMID- 15460928
TI  - When does visual perceptual grouping affect multisensory integration?
AB  - Several studies have shown that the direction in which a visual apparent motion
      stream moves can influence the perceived direction of an auditory apparent motion
      stream (an effect known as cross-modal dynamic capture). However, little is known
      about the role that intramodal perceptual grouping processes play in the
      multisensory integration of motion information. The present study was designed to
      investigate the time course of any modulation of the cross-modal dynamic capture
      effect by the nature of the perceptual grouping taking place within vision.
      Participants were required to judge the direction of an auditory apparent motion
      stream while trying to ignore visual apparent motion streams presented in a
      variety of different configurations. Our results demonstrate that the cross-modal
      dynamic capture effect was influenced more by visual perceptual grouping when the
      conditions for intramodal perceptual grouping were set up prior to the
      presentation of the audiovisual apparent motion stimuli. However, no such
      modulation occurred when the visual perceptual grouping manipulation was
      established at the same time as or after the presentation of the audiovisual
      stimuli. These results highlight the importance of the unimodal perceptual
      organization of sensory information to the manifestation of multisensory
      integration.

PMID- 15460929
TI  - Unimodal and crossmodal effects of endogenous attention to visual and auditory
      motion.
AB  - Three experiments were conducted examining unimodal and crossmodal effects of
      attention to motion. Horizontally moving sounds and dot patterns were presented
      and participants' task was to discriminate their motion speed or whether they
      were presented with a brief gap. In Experiments 1 and 2, stimuli of one modality
      and of one direction were presented with a higher probability (p = .7) than other
      stimuli. Sounds and dot patterns moving in the expected direction were
      discriminated faster than stimuli moving in the unexpected direction. In
      Experiment 3, participants had to respond only to stimuli moving in one direction
      within the primary modality, but to all stimuli regardless of their direction
      within the rarer secondary modality. Stimuli of the secondary modality moving in
      the attended direction were discriminated faster than were oppositely moving
      stimuli. Results suggest that attending to the direction of motion affects
      perception within vision and audition, but also across modalities.

PMID- 15460930
TI  - Catching audiovisual mice: predicting the arrival time of auditory-visual motion
      signals.
AB  - We investigated the extent to which auditory and visual motion signals are
      combined when observers are asked to predict the location of a virtually moving
      target. In Condition 1, the unimodal and bimodal signals were noisy, but the
      target object was continuously visible and audible; in Condition 2, the virtually
      moving object was hidden (invisible and inaudible) for a short period prior to
      its arrival at the target location. Our main finding was that the facilitation
      due to simultaneous visual and auditory input is very different for the two
      conditions. When the target is continuously visible and audible (Condition 1),
      the bimodal performance is twice as good as the unimodal performances, thus
      suggesting a very effective integration mechanism. On the other hand, if the
      object is hidden for a short period (Condition 2) and the task therefore requires
      the extrapolation of motion speed over a temporal and spatial period, the
      facilitation due to both sensory inputs is almost absent, and the bimodal
      performance is limited by the visual performance.

PMID- 15460931
TI  - Multisensory cortical processing of object shape and its relation to mental
      imagery.
AB  - Here, we used functional magnetic resonance imaging to investigate the
      multisensory processing of object shape in the human cerebral cortex and explored
      the role of mental imagery in such processing. Regions active bilaterally during
      both visual and haptic shape perception, relative to texture perception in the
      respective modality, included parts of the superior parietal gyrus, the anterior
      intraparietal sulcus, and the lateral occipital complex. Of these bimodal
      regions, the lateral occipital complexes preferred visual over haptic stimuli,
      whereas the parietal areas preferred haptic over visual stimuli. Whereas most
      subjects reported little haptic imagery during visual shape perception,
      experiences of visual imagery during haptic shape perception were common. Across
      subjects, ratings of the vividness of visual imagery strongly predicted the
      amount of haptic shape-selective activity in the right, but not in the left,
      lateral occipital complex. Thus, visual imagery appears to contribute to
      activation of some, but not all, visual cortical areas during haptic perception.

PMID- 15460932
TI  - The effect of temporal delay and spatial differences on cross-modal object
      recognition.
AB  - In a series of experiments, we investigated the matching of objects across visual
      and haptic modalities across different time delays and spatial dimensions. In all
      of the experiments, we used simple L-shaped figures as stimuli that varied in
      either the x or the y dimension or in both dimensions. In Experiment 1, we found
      that cross-modal matching performance decreased as a function of the time delay
      between the presentation of the objects. We found no difference in performance
      between the visual-haptic (VH) and haptic-visual (HV) conditions. Cross-modal
      performance was better when objects differed in both the x and y dimensions
      rather than in one dimension alone. In Experiment 2, we investigated the relative
      contribution of each modality to performance across different interstimulus
      delays. We found no differential effect of delay between the HH and VV
      conditions, although general performance was better for the VV condition than for
      the HH condition. Again, responses to xy changes were better than changes in the
      x or y dimensions alone. Finally, in Experiment 3, we examined performance in a
      matching task with simultaneous and successive presentation conditions. We failed
      to find any difference between simultaneous and successive presentation
      conditions. Our findings suggest that the short-term retention of object
      representations is similar in both the visual and haptic modalities. Moreover,
      these results suggest that recognition is best within a temporal window that
      includes simultaneous or rapidly successive presentation of stimuli across the
      modalities and is also best when objects are more discriminable from each other.

PMID- 15460933
TI  - Vicarious responses to pain in anterior cingulate cortex: is empathy a
      multisensory issue?
AB  - Results obtained with functional magnetic resonance imaging show that both
      feeling a moderately painful pinprick stimulus to the fingertips and witnessing
      another person's hand undergo similar stimulation are associated with common
      activity in a pain-related area in the right dorsal anterior cingulate cortex
      (ACC). Common activity in response to noxious tactile and visual stimulation was
      restricted to the right inferior Brodmann's area 24b. These results suggest a
      shared neural substrate for felt and seen pain for aversive ecological events
      happening to strangers and in the absence of overt symbolic cues. In contrast to
      ACC 24b, the primary somatosensory cortex showed significant activations in
      response to both noxious and innocuous tactile, but not visual, stimuli. The
      different response patterns in the two areas are consistent with the ACC's role
      in coding the motivational-affective dimension of pain, which is associated with
      the preparation of behavioral responses to aversive events.

PMID- 15460934
TI  - Why stop at HIPAA? Getting back on the healthcare information highway.
AB  - Both President Bush and his Democratic challenger, Senator John Kerry, are
      looking at new breakthroughs in healthcare information technology (IT) as the
      next best thing for the industry--and more important politically, as a key to
      making the delivery of health care more efficient and cost-effective.

PMID- 15460935
TI  - Cook County Hospital "from the 19th century straight to the 21st".
AB  - Chicago is home to the nation's oldest public hospital, Cook County Hospital.
      Once considered Chicago's Ellis Island, the old hospital served countless
      immigrants, indigents, and uninsured for almost 90 years.

PMID- 15460936
TI  - Two numbers you need to know.
AB  - By examining two numbers--managed care denial and recovery rates--hospitals can
      assess the effectiveness of their denial management efforts and payer performance
      and best focus efforts on payer contract compliance to achieve prompt payment.

PMID- 15460938
TI  - How are hospitals financing the future? Where the industry will go from here.

PMID- 15460937
TI  - Stark realities for hospitals.
AB  - As phase II of the Stark law becomes a reality, hospitals will find that the new
      physician self-referral regulations fall into three categories: the helpful, the
      unhelpful, and the marginal. Providers need to understand the principal changes
      in each category and modify their compliance efforts when compensating
      physicians.

PMID- 15460939
TI  - Cultural transformation for revenue cycle improvement.
AB  - More than technology is needed to bring about improvement in revenue cycle
      processes. A healthcare organization can transform its culture in several ways,
      including promoting a willingness to try new approaches and tools, investing in
      employee training and support, and rewarding behavior and processes that produce
      results.

PMID- 15460941
TI  - More dollars and more smiles.
AB  - Healthcare organizations can enhance customer satisfaction by identifying problem
      points along the revenue cycle and using key performance metrics to resolve those
      issues. They can establish metrics for revenue-cycle customer satisfaction by:
      Mapping the process to identify touch points. Confirming touch points and asking
      employees for their perceptions. Talking to patients and families. Conducting
      research.

PMID- 15460940
TI  - Endangered species? Not-for-profit hospitals face tax-exemption challenge.
AB  - The recent decision by the Illinois Department of Revenue to revoke the tax
      exempt status of Provena Covenant Medical Center is just one indication of a
      larger trend in which states are increasingly questioning the exchange of social
      contributions by not-for-profit hospitals for favorable tax treatment. As yet,
      there is no consensus on how charity care or community benefits should be
      measured. Results of a study examining different states' specifications of
      charity care indicate that alternate definitions of charitable contributions have
      a material effect on the total dollars recognized as charitable contributions.
      Such differences could have a bearing on any state's decision regarding whether a
      hospital should be allowed to retain its tax-exempt status.

PMID- 15460942
TI  - Freestanding heart hospitals is the end near?
AB  - Freestanding heart hospitals are not enjoying the same competitive advantages
      they have in recent years for several reasons: Regulatory policy seems to be
      turning against them. They no longer enjoy the same cost structure advantage.
      Technology shifts mean lower payment rates and higher costs for cardiac services.
      Their access to capital is diminished. Traditional hospitals are mounting more
      effective competitive responses, while entrepreneurial physician practice
      executives are pursuing alternative strategies that may lead to more competition
      for heart hospitals.

PMID- 15460943
TI  - The end is in FASB's sights.
AB  - The provisions of SFAS Nos. 145,146, and 132 (revised), which all became
      effective before June 30, 2004, should provide important guidelines for many
      types of healthcare organizations that engage in certain debt refinancing, sale
      leaseback transactions, and exit and disposal activities, as well as those that
      offer pension and postretirement employee benefits.

PMID- 15460944
TI  - Align process with mission and maintain a contented workforce.
AB  - Some hospitals are holding down costs, improving patient care, and maintaining a
      satisfied workforce by redesigning their processes. A four-step approach can
      ensure systemic and permanent cost reduction that doesn't compromise patient
      care, demoralize staff, or increase costs in other areas: 1. Prioritize core
      processes. 2. Implement a disciplined process redesign methodology. 3. Review
      proposed changes with process owners and members. 4. Secure top management
      approval and sponsorship.

PMID- 15460945
TI  - The road to better care: merging financial and clinical pathways.

PMID- 15460946
TI  - 5 steps to creating a winning culture.

PMID- 15460947
TI  - Marrying technology and process change for improved revenue management.

PMID- 15460948
TI  - The case for customer loyalty.
AB  - How does customer loyalty grow? Through good customer experiences. Yet some
      organizations seem to genuinely fail to understand that they can keep or lose a
      customer in the proverbial blink of an eye. And in this era of increasing
      customer demands across all industries, it's important that healthcare financial
      managers understand the correlation between customer loyalty and customer
      experience.

PMID- 15460949
TI  - Identifying the best revenue-recovery opportunities.

PMID- 15460950
TI  - Vaccine preventable diseases and vaccination coverage in Aboriginal and Torres
      Strait Islander people, Australia, 1999 to 2002.
AB  - This report complements the Vaccine Preventable Diseases and Vaccination Coverage
      reports produced biannually since 2000 by the National Centre for Immunisation
      Research and Surveillance of Vaccine Preventable Diseases in association with the
      Australian Institute of Health and Welfare. It integrates the available sources
      of routinely collected data relevant to the current status of vaccine preventable
      diseases and vaccine coverage in Aboriginal and Torres Strait Islander people in
      Australia. It aims to better inform Indigenous communities, Indigenous health
      care providers and planners of immunisation services of the current status and
      future needs for vaccine prevention in Indigenous people. The data presented here
      demonstrate that vaccination programs have had a significant impact on the health
      of Aboriginal and Torres Strait Islander people. Several areas are highlighted
      for further development of vaccination policy recommendations, in particular high
      rates of preventable hepatitis A and B, influenza and pneumococcal disease. Areas
      where more research is needed include means to more accurately monitor
      vaccination status, the applicability of meningococcal serogroup B vaccines when
      available, and effective ways of increasing vaccination coverage and timeliness
      of vaccination. Such issues need to be considered and implemented in full
      cooperation with Aboriginal and Torres Strait Islander people.

PMID- 15460951
TI  - Annual report of the National Influenza Surveillance Scheme, 2003.
AB  - Surveillance of influenza in Australia is based on laboratory isolation of
      influenza viruses, sentinel general-practitioner practices for influenza-like
      illness, and absenteeism data from a major national employer. In 2003, the peak
      in influenza activity was in August which was later than in 2002. In 2003, 3,604
      laboratory-confirmed cases of influenza were notified to the National Notifiable
      Diseases Surveillance System, which was marginally lower than for the previous
      year. Ninety-four per cent of the circulating viruses were influenza A. This was
      the highest proportion in the last five years. Nine hundred and thirty-five
      isolates were antigenically analysed: 928 were A(H3), two were A(H1) strains and
      five were influenza B viruses. The majority (98%) of the A(H3) subtypes were
      A/Fujian/411/2002(H3N2)-like and have shown a significant antigenic drift. The
      2003 Australian influenza vaccine contained A/Panama/2007/99, which induced 2-4
      fold lower antibody response against the drifted strain. An
      A/Fujian/411/2002(H3N2)-like virus has been incorporated in the Australian
      influenza vaccine for 2004. In 2003, the influenza vaccine was given to 77 per
      cent of Australians aged over 65 years; the same up take as in 2002.

PMID- 15460952
TI  - The Influenza Surveillance Program in Western Australia, 2003.
AB  - In the winter of 2003 Western Australia experienced its largest epidemic of
      influenza for at least five years, with activity peaking in August and September.
      The season was short resulting in very high numbers of cases during the peak
      weeks. Activity in country areas followed the peak of Metropolitan activity.
      Influenza A virus was detected in 28.3 per cent of the sentinel samples, and
      influenza B in less than one per cent. Both routine and sentinel detections and
      the overall estimates of influenza-like illnesses (ILI) seen by general
      practitioners at sentinel practices peaked in August and September 2003. The
      combination of influenza detections and an increase in ILI seemed to be the most
      accurate predictor of the beginning of winter influenza activity. There was a
      shift in age distribution for influenza A compared with 2003. Both the sentinel
      surveillance and routine samples demonstrated an increase of influenza in
      children and young adults. The majority of influenza A isolates were identified
      as A/Fujian/411/2002-like, a variant of the A/Moscow strain included in the
      vaccine. Despite this mismatch there did not seem to have been any noticeable
      increase in the risk of influenza infection in the vaccinated populations from
      the sentinel practices, nor was there a relative increase in disease among the
      highly vaccinated elderly population. A number of other respiratory viruses were
      identified as causes of influenza-like illness in the sentinel samples.
      Rhinoviruses and human metapneumovirus were the most common, the latter occurring
      mainly in adults.

PMID- 15460953
TI  - Higher than normal seasonal influenza activity in Victoria, 2003.
AB  - Influenza surveillance in Victoria comprises surveillance of patients with
      influenza-like illness (ILI) from sentinel general practices and laboratory based
      reporting of influenza detections, predominantly from hospital inpatients.
      Surveillance of patients with ILI seen by the Melbourne Medical Locum Service
      (MMLS) was conducted for the first time in 2003, when the influenza season was
      characterised by a late onset with higher than normal seasonal activity.
      Influenza A (H3N2) was the predominant circulating influenza virus type, with 99
      per cent of sub-typed viruses identified as a drifted strain, A/Fujian/411/2002
      like. Sentinel and hospital laboratory surveillance both indicated low levels of
      circulating influenza A (H1N1) and influenza B. Although the proportion of
      patients with ILI detected through MMLS surveillance was greater than the
      proportion from sentinel general practices, the ILI pattern was comparable
      between the two surveillance systems.

PMID- 15460954
TI  - Severe acute respiratory syndrome surveillance in Australia.
AB  - In March 2003, the World Health Organization (WHO) issued a global alert
      recommending active worldwide surveillance for severe acute respiratory syndrome
      (SARS). This paper describes the epidemiological features of cases reported by
      Australian states and territories to the Australian Government Department of
      Health and Ageing between 17 March and 31 July 2003. There were 138 people
      investigated for SARS: 111 as suspect and 27 as probable. Five probable cases
      were reported to WHO after review of other possible diagnoses and Australia
      specific exclusion criteria had been applied. An additional probable case
      identified by laboratory testing overseas, but who was not under investigation
      when in Australia, was also reported to WHO. The method by which surveillance for
      SARS was rapidly established provided an opportunity to examine Australia's
      planning and preparedness for future respiratory disease epidemics such as
      influenza.

PMID- 15460955
TI  - Annual report of the Australian Gonococcal Surveillance Programme, 2003.
AB  - The Australian Gonococcal Surveillance Programme monitors the antibiotic
      susceptibility of Neisseria gonorrhoeae isolated in all Australian states and
      territories. In 2003 the in vitro susceptibility of 3,772 isolates of gonococci
      from public and private sector sources was determined by standardised methods.
      Antibiotic susceptibility patterns again varied considerably between
      jurisdictions and regions. Resistance to the penicillins nationally, was 17 per
      cent but ranged up to 27 per cent in larger urban centres. Quinolone resistance
      in gonococci (QRNG) remained widespread and increased in most states but most
      markedly in Victoria. Nationally, 14.4 per cent of all isolates were QRNG, and
      most of this resistance was at high MIC levels. All isolates remained sensitive
      to spectinomycin. A small number of isolates showed some decreased susceptibility
      to ceftriaxone (MIC 0.06 mg/L or more) and were concentrated in New South Wales.
      A high proportion of gonococci examined in larger urban centres were from male
      patients and rectal and pharyngeal isolates were common. In other centres and in
      rural Australia the male to female ratio of cases was lower, and most isolates
      were from the genital tract. In New South Wales, the number of available cultures
      decreased and represented 30 per cent of the national total. In Victoria, the
      number of isolates increased and was 25 per cent of all gonococci examined.

PMID- 15460956
TI  - Annual report of the Australian Meningococcal Surveillance Programme, 2003.
AB  - This tenth report by the National Neisseria Network, a nation-wide collaborative
      laboratory program, describes 494 laboratory-confirmed cases of meningococcal
      disease in Australia, diagnosed in 2003. The phenotypes (serogroup, serotype and
      serosubtype) and antibiotic susceptibility of 303 isolates of Neisseria
      meningitidis from invasive cases of meningococcal disease were determined, and an
      additional 191 cases were confirmed by non-culture-based methods. The age
      distribution of invasive meningococcal disease showed a typical primary peak in
      those aged four years or less which was predominantly serogroup B meningococci. A
      secondary peak in adolescents and young adults contained a larger proportion of
      serogroup C infections. Nationally, the majority of isolates were serogroup B
      (183 isolates, 60.4%) or serogroup C (102 isolates, 33.6%) meningococci. The
      number of serogroup C isolates in Victoria decreased from 72 in 2002 to 33 in
      2003 and in Tasmania the number of serogroup C isolates decreased from 14 to
      five. Smaller decreases in serogroup C isolate numbers were recorded in most
      other jurisdictions but the number increased in the Australian Capital Territory
      from four to seven isolates. Serogroup B isolate numbers also decreased
      nationally but by a smaller amount. However in South Australia serogroup B
      infections more than doubled, and there were also increases in the Northern
      Territory and Australian Capital Territory. The serogroup C phenotype C:2a:P1.4
      remained prominent in Victoria but elsewhere in Australia it was detected only in
      low numbers. About two thirds of all isolates showed decreased susceptibility to
      the penicillin group of antibiotics (MIC 0.06 to 0.5 mg/L). A single isolate from
      the Australian Capital Territory was penicillin resistant at 1 mg/L and two, one
      each from South and Western Australia were rifampicin resistant.

PMID- 15460957
TI  - OzFoodNet: enhancing foodborne disease surveillance across Australia: quarterly
      report, January to March 2004.
AB  - Salmonella incidence increased during the quarter and was responsible for 46 per
      cent of foodborne outbreaks. Large numbers of norovirus outbreaks continued to be
      reported in aged care facilities and hospitals. Several outbreaks were related to
      eggs, although traceback efforts were unsuccessful. A third outbreak of norovirus
      implicating a different brand of oysters imported from Japan was significant,
      resulting in action to remove the oysters from the marketplace. These outbreaks
      have resulted in reconsideration of the safety of oysters harvested from
      contaminated waters in other countries.

PMID- 15460958
TI  - Foodborne disease outbreaks in Australia, 1995 to 2000.
AB  - Health agencies are increasingly conducting systematic reviews of foodborne
      disease outbreak investigations to develop strategies to prevent future
      outbreaks. We surveyed state and territory health departments to summarise the
      epidemiology of foodborne disease outbreaks in Australia from 1995 to 2000. From
      1995 through 2000, 293 outbreaks were identified, with 214 being of foodborne
      origin. One hundred and seventy-four (81%) had a known aetiology, and accounted
      for 80 per cent (6,472/8,124) of illnesses. There were 20 deaths attributed to
      foodborne illness. Of the 214 outbreaks, bacterial disease was responsible for 61
      per cent of outbreaks, 64 per cent of cases and 95 per cent of deaths. The most
      frequent aetiology of outbreaks was Salmonella in 75 (35%) outbreaks, Clostridium
      perfringens in 30 (14%), ciguatera toxin in 23 (11%), scombrotoxin in 7 (3%) and
      norovirus in 6 (3%). Salmonellosis was responsible for eight of the 20 (40%)
      deaths, as was Listeria monocytogenes. Restaurants and commercial caterers were
      associated with the highest number of outbreak reports and cases. Outbreaks in
      hospitals and aged care facilities were responsible for 35 per cent of deaths.
      The most frequently implicated vehicles in the 173 outbreaks with known vehicles
      were meats 64 (30%), fish 34 (16%), seafood 13 (6%), salad 12 (6%), sandwiches 11
      (5%) and eggs 9 (4%). Chicken, the most frequently implicated meat, was
      associated with 27 (13%) outbreaks. This summary demonstrates the serious nature
      of foodborne disease and supports the move to risk-based food safety
      interventions focusing on mass catering and hospital and aged care facilities.

PMID- 15460959
TI  - An outbreak of shigellosis in a child care centre.
AB  - Outbreaks of shigellosis in child care are not commonly reported in Australia,
      however Shigella bacteria can easily spread in these settings. We report an
      outbreak of shigellosis in a child care centre and discuss the control measures
      implemented. This investigation identified 20 confirmed cases of Shigella sonnei
      biotype g and a further 47 probable cases in children and staff who attended a
      child care centre, and their household contacts. The investigation highlighted
      the importance of stringent control measures and protocols for dealing with
      outbreaks of Shigella and other enteric infections in the child care setting, and
      the importance of prompt notification by both doctors and child care centres, of
      suspected outbreaks.

PMID- 15460960
TI  - Passive surveillance of antimicrobial resistance in Queensland public hospitals:
      the basis for a national system?
AB  - Australia currently has no system of passive surveillance of antimicrobial
      resistance in spite of the importance of surveillance in identifying and defining
      emergent resistance being generally accepted. Queensland Health Pathology and
      Scientific Services have developed flexible software for passive surveillance
      with the capacity to handle national data. The system imports raw data strings in
      delimited ASCII text format into a relational database and screens to exclude
      duplicates before the processing of the cumulative susceptibility data. It allows
      considerable flexibility in inquiry parameters and has the ability to 'drill
      down' to individual laboratory results. Examples of analytical output are given
      for 49,169 unique isolate results obtained in all Queensland Health Pathology
      Service laboratories from 1 January to 30 June 2003. The system could form the
      basis of a national system for passive antimicrobial resistance surveillance.

PMID- 15460961
TI  - Was the egg a plausible source for the Salmonella Potsdam outbreak?

PMID- 15460962
TI  - What do we know about 7vPCV coverage in Aboriginal and Torres Strait Islander
      children?
AB  - In 2001, a publicly funded pneumococcal conjugate vaccine (7vPCV) program
      commenced for Aboriginal and Torres Strait Islander children aged under two
      years. At present, there is very little knowledge about the uptake of 7vPCV
      vaccine amongst Aboriginal and Torres Strait Islander children. This study
      examined the rollout and use of 7vPCV vaccine in Australia and estimated
      immunisation coverage for Indigenous children at the age of 12 months for 7vPCV
      vaccine. To calculate 7vPCV coverage we chose four consecutive 3-month birth
      cohorts born between 1 October 2001 and 30 September 2002. The immunisation
      status of children in each birth cohort was assessed at 12 months for the third
      dose of 7vPCV vaccine. The largest absolute number of 7vPCV doses was given in
      Queensland, the Northern Territory and New South Wales. As the 7vPCV program
      matured, a progressively higher proportion of total doses was administered to
      children under the age of 12 months consistent with the introduction of the
      program. For all jurisdictions except the Northern Territory and Western
      Australia, where it has remained reasonably constant, estimated coverage
      increased over the most recent birth cohorts but was still less than 50 per cent
      for all states except the Northern Territory, Queensland, and Western Australia.
      This study provides the first national measure of 7vPCV immunisation coverage
      among Indigenous children in Australia. With the likely improvement over time in
      the recording of 7vPCV vaccinations and Indigenous status on the Australian
      Childhood Immunisation Register, the validity of coverage estimates is likely to
      increase.

PMID- 15460963
TI  - Age-related risk of adverse events following yellow fever vaccination in
      Australia.
AB  - Reports of six deaths internationally, including one from Australia, plus other
      cases of severe systemic adverse events following yellow fever (YF) vaccination
      have raised concern about the safety of YF vaccine, particularly among older
      vaccinees. We investigated the age-related reporting rates of adverse events
      following YF vaccination reported to the Australian Adverse Drug Reactions
      Advisory Committee for the period 1993 to 2002. The reporting rate of systemic
      adverse events leading to hospitalisation or death was significantly higher among
      vaccinees aged > or = 65 years [reporting rate ratio (RRR) 8.95, 95% confidence
      interval (CI) 1.49-53.5] or > or = 45 years (RRR 5.30, 95% CI 1.33-21.2) compared
      with younger YF vaccinees. The higher reporting rates among older vaccinees are
      similar to those identified in the United States of America. The data highlight
      the importance of assessing the destination-specific risk, especially for older
      travellers to yellow fever endemic areas, and careful monitoring of those who are
      vaccinated.

PMID- 15460964
TI  - Planning for human papillomavirus vaccines in Australia; report of a research
      group meeting.

PMID- 15460965
TI  - Impact of Haemophilus influenzae type b (Hib) vaccination on Hib meningitis in
      children in Far North Queensland, 1989 to 2003.
AB  - Over the four years 1989 to 1992 there were 28 cases of Haemophilus influenzae
      type b (Hib) meningitis in children aged under five years in Far North
      Queensland. Thirteen (46%) of the cases were in Indigenous children, indicating
      that the rate of the disease was about 3.5 times greater in these children than
      in non-Indigenous children. However, no cases of Hib meningitis have occurred in
      Indigenous children in Far North Queensland in the 10 years following the
      addition of Hib vaccines to the Australian Standard Vaccination Schedule in 1993.
      There was only one case of Hib meningitis, in a (vaccinated) non-Indigenous
      child, between 1994 and 2003. About 70 cases of Hib meningitis in children were
      prevented by Hib immunisation in Far North Queensland between 1994 and 2003;
      possibly as many as five deaths and 12 cases with neurological sequelae were also
      prevented.

PMID- 15460966
TI  - Trends in potential exposure to Australian bat lyssavirus in South East
      Queensland, 1996 to 2003.
AB  - This study examined trends in notifications of potential exposure to Australian
      bat lyssavirus reported to the Brisbane Southside Public Health Unit, Australia
      between 1 November 1996 and 31 January 2003. Notification rates declined among
      all population groups and potential exposures were notified more promptly.
      Concern exists regarding possible under-reporting of potential exposure to
      Australian bat lyssavirus especially among volunteer bat carers.

PMID- 15460967
TI  - Ross River virus and its vectors in Sorell Municipal Area, south-eastern
      Tasmania, January to March 2002.
AB  - In 2002, Tasmania reported the largest number of Ross River virus (RRV)
      infections ever recorded for the state. Of the 117 cases, 37 lived in, or had
      visited, the Sorell Municipal Area, east of Hobart. In early 2002, a combination
      of spring tides and high summer rainfall produced extensive salt marsh habitat in
      the Sorell region, resulting in unseasonably high densities of the mosquito
      Ochlerotatus camptorhynchus, recognised vector of RRV. Four isolates of RRV were
      identified from collections of adult mosquitoes. All four isolates were from Oc.
      camptorhynchus, collected near the Carlton River. This is the furthest south that
      RRV has been identified in Australia and the first identification from south-east
      Tasmania. The virus carriage rate in the mosquito vector populations were very
      high, with successive weekly minimum infection rates of 17.1, 3.0 and 11.1 per
      1,000 Oc. camptorhynchus at Carlton River from mid-February to early March. The
      first isolation of RRV from mosquitoes coincided with the onset dates of the
      first human cases of RRV infection.

PMID- 15460968
TI  - Scrub typhus in the Northern Territory: exceeding the boundaries of Litchfield
      National Park.
AB  - Scrub typhus is recognised as an important differential diagnosis of fever, rash
      and sepsis in patients with a history of travel to Litchfield National Park in
      the Top End of the Northern Territory. All confirmed scrub typhus cases to date
      from the Northern Territory have visited the Park, but the presence of similar
      rainforest pockets elsewhere in the Top End suggested further infectious
      locations might be identified with increased tourism. We report a case of
      serologically confirmed Orientia tsutsugamushi infection in a man who had not
      been within Litchfield Park, but had visited another discrete Top End rainforest
      area.

PMID- 15460969
TI  - Follow-up of communicable diseases reported among travellers on aeroplanes.

PMID- 15460970
TI  - Role of the National Centre in HIV Epidemiology and Clinical Research in
      surveillance for HIV/ AIDS, viral hepatitis and sexually transmissible infections
      in Australia.

PMID- 15460971
TI  - A report from the Communicable Diseases Network Australia, January to March 2004.

PMID- 15460972
TI  - Changes to the management of meningococcal disease in Australia.

PMID- 15460973
TI  - Communicable diseases surveillance. Highlights for 1 st quarter, 2004.

PMID- 15460974
TI  - The person approach: concepts, measurement models, and research strategy.

PMID- 15460975
TI  - A person-oriented approach: methods for today and methods for tomorrow.

PMID- 15460976
TI  - Patterns and pathways of educational achievement across adolescence: a holistic
      developmental perspective.

PMID- 15460977
TI  - The transition to high school: a prodigal analysis of developmental pathways.

PMID- 15460978
TI  - Heterogeneity in the relationship between popularity and aggression: individual,
      group, and classroom influences.

PMID- 15460979
TI  - A pattern-centered approach to evaluating substance use prevention programs.

PMID- 15460981
TI  - [The correlation dependence between urinary excretion of vitamin B1, B2, C and
      entrance some nutrients with ration].
AB  - The results of the correlation analysis between parameters of urinary excretion
      of vitamins B1, B2 and ascorbic acid and the consumption of some nutrients with
      daily ration are presented. The expressed correlation dependence between
      consumption of proteins and fats and urinary excretion of riboflavin, and between
      consumption of proteins and carbohydrates and urinary excretion of ascorbic acid
      were found out. The strong correlation was found between the level of the
      majority trace elements in daily ration and urinary excretion of vitamins. The
      urinary excretion of thiamin, riboflavin and ascorbic acid depends on their
      quantity consumed with the daily ration.

PMID- 15460980
TI  - [The influence of panthotenic acid mitochondrial oxidation and oxidative
      phosphorylation in liver of rats with alimentary obesity].
AB  - Alimentary obesity induced by the long-term feeding of rats by high-fat diet
      results the reducing of rate and efficiency of oxidative phosphorylation in liver
      mitochondria when NAD-dependent substrates are used. The treatment of the obese
      rats with panthotenic acid derivatives (phosphopantotenate, panthetin, panthenol)
      enhanced oxidative phosphorylation of pyruvate and fatty acid carnitine esters.
      Among investigated compounds panthenol activated respiratory control and
      phosphorylation rate more effectively. Moreover, panthenol, but not
      phosphopanthotenate nor panthetine, increased the activity of carnitine
      palmitoyltransferase 1 that confirms the preferable usage of fatty acids for
      mitochondrial oxidation under the influence of this compound.

PMID- 15460982
TI  - [Long-term outcomes after acute vitamin D3 intoxication].
AB  - We observed 75 subjects with acute vitamin D3 intoxication (AVD3I). The clinical
      manifestations of this intoxication are kidneys disorders (65.0%), renal
      insufficiency (51.0%), gastrointestinal tract disorders (23.0%), arterial
      hypertension (52.0%). After this intoxication these patients are recommended
      prolonged rehabilitation.

PMID- 15460983
TI  - [The application vitamins of patients with atopy: a risk or the realized
      necessity?].
AB  - The research showed that allergic reactions mostly not develop not to vitamins
      themselves but to dyes and flavorings. Prescription of vitamins with hypoallergic
      formula (e.g. Vitrum Junior) is not only realized but also necessary as an
      important containing part of complex treatment of allergic diseases. Risk of
      development of allergic manifestations during the period of taking of vitamins is
      decreased and provocative paros tests have been processed before.

PMID- 15460984
TI  - [Effect of a zinc-enriched diet on the clinical and metabolic parameters in type
      2 diabetic patients].
AB  - It was investigated the influence of a diet with zinc supplementation on dynamic
      of glycaemia, lipid profile, blood pressure and weight in type 2 diabetic
      patients. Traditional hypocaloric diet was supplemented with zinc-spirulina (7.5
      mg zinc per day). The results investigations indicated that a zinc-enriched diet
      has beneficial effects on basal and postprandial glycaemia, the content of
      cholesterol and triglycerides in serum in compared with a traditional hypocaloric
      diet.

PMID- 15460986
TI  - [About raising the sanitary culture of food industry's workers].
AB  - The article includes: the basic problems of sanitary teaching of professional
      population groups, also the structure of training aids and examination tasks of
      sanitary knowledge for food industry's workers.

PMID- 15460985
TI  - [Use of the syrup prepared on the basis of wild-growing grasses of the Far East,
      in preventive maintenance of respiratory diseases and microelementoza at
      children].
AB  - Working out formula and techology of producing the syrup, which is based on herbs
      of Far Eastern Region (dog rose; leaves of currant, lime-tree; herbs St. John's
      wort, parsley. Nettle; licorice) and food dietary supplements--Laminal (the
      product of processing of brown seaweeds). Here are the results of the research
      work of chemical contents, energetic value, minor componential contents and
      microbiological values of syrup. The results of approbation of the syrup on the
      group of children (who catch a cold very often) showed the increase of
      coefficient of special immune lymphocytic-monocytical and cell-phagocytal
      protection. These results allow us to recommend it as a kind of treatment,
      included in health-improvement program.

PMID- 15460987
TI  - [Actual evaluation of nutrition in different children age groups].
AB  - Children actual nutrition research in Novomoskovsk in different age groups 4-5, 9
      10, 12-13 and 15-16 revealed the existence of the main food component shortage,
      nutrient and aminoacid disbalance, and also the reduction of the power value of
      the daily nutrition. Within the years the specific gravity of children with
      protein, fat and carbohydrate, shortage has the marked tendency towards the
      reduction, the specific gravity with the shortage of C, A, B2, B6, B12 vitamins
      and also with iron shortage among the girls has the tendency towards the
      increase.

PMID- 15460988
TI  - [Selenium safety in children with protracted diarrhea syndrome].
AB  - The insufficient selenium safety was revealed in 27% of the children without
      signs of intestinal absorption damage surveyed in Novokuznetsk. Patients with
      coeliac disease differ doubtfully on a parameter of selenium safety from patients
      of control group whereas serum selenium level rises while keeping gluten free
      diet. Selenium insufficiency was observed approximately in 2/3 of children with
      allergic enteropathia and intestinal absorption damage of obscure origin. It is
      supposed, that the basic reason of selenium insufficiency in children with
      protracted diarrhea is a violation of intestinal protein absorption. The
      assumption failed that exception of grain products from diet in coeliac disease
      leads to selenium insufficiency. Children suffering from protracted diarrhea may
      need in correction of their selenium status.

PMID- 15460989
TI  - [Role tunica mucosa small intestinal in exchange processes].
AB  - The review of the experimental and clinical data confirming active participation
      small intestinal in exchange processes at a pathology of bodies of digestion and
      malnutrition. The features of assimilation and turnover protein of a diet in
      small intestinal.

PMID- 15460990
TI  - [Determination of fat-soluble vitamins and carotenoids in food additives using
      high-performance liquid chromatography].
AB  - Wide diversity of fat-soluble vitamins and carotenoids, their ability for
      isomerization and oxidation under action of a range of physical and chemical
      factors stimulates the development of modern selective methods for determination
      of individual compound contents of these substantial micronutrients. It is
      important to determine separately the geometric cis- and trans-isomers, which
      exhibit different vitamin and antioxidant activity. Use of high performance
      liquid chromatography in combination with various methods of sample pre-treatment
      for this purpose makes possible to determine simultaneously in automatic run the
      fat-soluble vitamins A, E, D, K and carotenoids as well as their isomers with
      high sensitivity and selectivity. The adequate estimation of vitamin value of
      foods and food additives is thus achieved.

PMID- 15460991
TI  - [C-reactive protein: its physical and chemical properties, structure and specific
      properties].

PMID- 15460992
TI  - [170 years of using the sulfosalicylyl method (literature review)].

PMID- 15460993
TI  - [The lanthanide fluorescence immunoassay of the total thyroxin in dried
      bloodstains on paper].
AB  - The lanthanide fluorescence immunoassay was elaborated for quantitative
      determination of the total thyroxin T4 in bloodstain dried in filter paper; the
      fields of its clinical application were defined. The method is based on the
      hardphase concurrent immunoassay with specific monoclonal antibodies to T4 marked
      by chelates of europium ions and with conjugate of the T3 heterologous hapten
      sorbed in plate holes with bovine serum albumin. Measurements of the fluorescence
      intensity were made by a fluorometer in the time resolution mode. The method
      ensures the T4 determination in a dry bloodstain with a diameter of 3.4 mm within
      the concentration range of 0 to 400 nmol/l and with the variation coefficient of
      below or equal to 15%; the results correlated with the findings of the T4
      analysis by the DELFIA Neo T4 set, "Wallac Oy", Finland. The method efficiency
      was demonstrated for screening and verifying the congenital thyroid deficiency in
      newborns; it was also confirmed that the method can be used for monitoring the
      functional thyroid condition in adult patients.

PMID- 15460994
TI  - [Physical and chemical characteristics of structurization of a biological fluid
      drop as examplified by the "LITOS-system" diagnosticum].

PMID- 15460995
TI  - [The clinical and diagnostic significance of laboratory examinations in
      prognosticating the clinical course of craniocerebral trauma].

PMID- 15460996
TI  - [A method of quantitative evaluation of oxygen-dependent metabolism in human
      neutrophil granulocytes].

PMID- 15460997
TI  - [Blood rheological properties and their interrelation with pulmonary hypertension
      in patients with chronic dust bronchitis].
AB  - Nineteen patients with chronic obstructive disease of the lungs and 15 patients
      with chronic non-obstructive bronchitis of the dust etiology were examined for
      the purpose of investigating the rheological blood properties and of their
      interrelation with pulmonary hypertension. The hemorheological properties were
      evaluated by spontaneous aggregation of erythrocytes and thrombocytes. The
      control group comprised 8 healthy subjects. The results denoted that the
      rheological blood properties are to a great extent impaired in patients with dust
      bronchitis. The rheological blood properties worsened as hypertension of the
      small blood-circulation circle was increasing; it preceded the development of
      pulmonary hypertension in patients with chronic obstructive disease of the lungs.
      The aggregation changes appear to be primarily related with the functional state
      of thrombocytes in patients with chronic non-obstructive bronchitis; a
      concurrently higher aggregation of thrombocytes and erythrocytes was observed in
      patients with chronic obstructive disease of the lungs. The obtained data can be
      useful for designing a medicamental correction scheme of rheological impairments
      as a trend within the treatment of affected hemodynamics in the small blood
      circulation circle in patients with duct bronchitis.

PMID- 15460998
TI  - [Reactivity of buccal epitheliocytes: indication of local and general impairment
      in hemostasis (a literature review)].

PMID- 15460999
TI  - [A comparative morphological description of the gingival and buccal epithelium in
      females in various phases of the menstrual cycle].
AB  - Computer morphometry was used to analyze morphologically and histochemically the
      smears of the gingival and buccal epithelium obtained from women at the secretion
      and proliferation phases of the menstrual cycle. A variety of reliably statistic
      differences conditioned by a menstrual-cycle phase was found to be typical of the
      gingival epithelium. A high percentage of epitheliocytes of differentiation
      terminal stages as well as signs of enhanced protein-synthesizing processes were
      typical of the cells ratio in the gingival epithelium at the secretion phase. The
      number of differences in the buccal epithelium conditioned by a menstrual cycle
      was by far less, which denotes a lesser dependence of this epithelium on
      hormones, whose concentration at the proliferation phase essentially differs from
      that observed at the secretion phase.

PMID- 15461000
TI  - [A cytological study as a part of integrated examinations of patients with the
      mammary gland pathologies in the ambulatory and clinical settings].
AB  - An integrated system of examination of female patients was used to detect the
      mammary-gland pathologies at the Central Clinic of Russia's Federal Security
      Service in the ambulatory and clinical settings. Fine-needle aspiration biopsy
      monitored by ultrasound as well as target aspiration biopsy based on the
      "Mammodiagnost-400" X-ray unit with the "Cytoguide" stereoscopic attachment
      (pistol-needle system) were applied to obtain the cell samples in nonpalpable
      neoplasms of the mammary gland; fine-needle aspiration biopsy without ultrasound
      monitoring was used in palpable neoplasms. Diagnosis was morphologically verified
      in all cases. Pathologies of the mammary gland prevailed, within the examinees,
      at an age of 44 to 53. The number of malignant neoplasms made 7.6% of the total
      number of examinees. The results of intraoperative cytological examinations
      correlated, in all cases, with histological conclusions. The final diagnosis was
      made on the basis of clinical and X-ray examinations and of cytological
      conclusions. The diagnosis was histologically verified in 40% of cases. According
      to the data analysis, histological examinations are necessary and should be in
      the list of diagnosis-verification measures within the system of integrated
      examinations of female patients with pathologies of the mammary gland.

PMID- 15461001
TI  - [Determination of the level of antibodies to CD4 in serum of patients with
      malignant lymphomas and of HIV-infected individuals].
AB  - Hardphase ELISA was used to compare the blood sera of patients with malignant
      skin lymphomas and HIV infection and of healthy volunteers for autoimmune
      antibodies to CD4. Antibodies to CD4 were not detected in the volunteers (30
      sera) and in the patients with malignant skin lymphomas (52 patients with
      different disease stages). The antibodies were found in 4 of 11 HIV cases.

PMID- 15461002
TI  - [Detection of antibodies to HIV virus in saliva by express-tests in Uzbekistan].
AB  - Saliva tests, when used in screening for antibodies to HIV virus (anti-HIV),
      makes testing safer, easy-to-fulfill (even outside clinic) and acceptable for a
      majority of examinees. The main quality parameters of express-test for the
      detection of anti-HIV in saliva were evaluated for the purpose of using the
      related approach in the HIV epidemiological supervision. Saliva samples and sera
      of 81 HIV-infected patients and of 99 presumably non-infected persons were
      investigated by the "OraQuick" express-test. The data obtained were compared with
      the results of ELISA-based serum testing. The sensitivity of "OraQuick" made 95%
      and its specificity was 100%. The test is appropriate for epidemiological
      investigations and HIV epidemiological supervision but it cannot be recommended
      for the blood transfusion service.

PMID- 15461003
TI  - [The cytokine profile of blood serum in women with missed abortion].

PMID- 15461004
TI  - [Detection of antibiotic contents in cerebrospinal fluid].
AB  - The suggested method provides for the semi-quantitative detection of antibiotics
      in liquor made for the purpose of prognosticating the possibility of cultural
      secretion of infectious agents of purulent bacterial meningitis (PBM); it is also
      a basis for the need in using the non-cultural diagnostic tools. The method can
      be used in detecting the pharmacokinetic specificity of antibacterial drugs now
      in use and of their combinations with the aim of making corrections in antibiotic
      therapy. It is based on inhibiting the surface growth of test-culture by a liquor
      dissolved antibiotic with the growth-delay zone being shaped. The preparation
      concentration is estimated in U/ml of the penicillin equivalent (PE).
      Examinations of 131 liquor samples (primary puncture) obtained from patients with
      meningitis showed clear-cut correlations between the antibiotics' concentrations,
      cultural verification of the PBM diagnosis and the efficiency of non-cultural
      examinations. 82.14% of cultures were derived from liquor samples with the
      negative antibacterial activity (range 1); 7.14% of cultures were derived from
      liquor samples containing the antibacterial preparation of up to 0.5 U/ml PE
      (range 2); culture of secondary PBM agents (S. aureus) were isolated from liquor
      samples containing up to 10 U/ml PE (range 3); and no microbe agents were
      isolated from liquor samples containing above 10 U/ml PE (range 4). The designed
      method, when used, demonstrated a high efficiency and significance of laboratory
      PBM diagnosis in presence of the antibacterial liquor efficiency.

PMID- 15461005
TI  - [Laboratory diagnosis of natural focus tick-borne infections].

PMID- 15461006
TI  - [Evaluation of the economic efficiency of using the closed systems for biological
      sampling at a multi-purpose laboratory].

PMID- 15461007
TI  - Paradox lost: explaining the Hispanic adult mortality advantage.
AB  - We tested three competing hypotheses regarding the adult "Hispanic mortality
      paradox": data artifact, migration, and cultural or social buffering effects. On
      the basis of a series of parametric hazard models estimated on nine years of
      mortality follow-up data, our results suggest that the "Hispanic" mortality
      advantage is a feature found only among foreign-born Mexicans and foreign-born
      Hispanics other than Cubans or Puerto Ricans. Our analysis suggests that the
      foreign-born Mexican advantage can be attributed to return migration, or the
      "salmon-bias" effect. However, we were unable to account for the mortality
      advantage observed among other foreign-born Hispanics.

PMID- 15461008
TI  - Resolving inconsistencies in trends in old-age disability: report from a
      technical working group.
AB  - In September 2002, a technical working group met to resolve previously published
      inconsistencies across national surveys in trends in activity limitations among
      the older population. The 12-person panel prepared estimates from five national
      data sets and investigated methodological sources of the inconsistencies among
      the population aged 70 and older from the early 1980s to 2001. Although the
      evidence was mixed for the 1980s and it is difficult to pinpoint when in the
      1990s the decline began, during the mid- and late 1990s, the panel found
      consistent declines on the order of 1%-2.5% per year for two commonly used
      measures in the disability literature: difficulty with daily activities and help
      with daily activities. Mixed evidence was found for a third measure: the use of
      help or equipment with daily activities. The panel also found agreement across
      surveys that the proportion of older persons who receive help with bathing has
      declined at the same time as the proportion who use only equipment (but not
      personal care) to bathe has increased. In comparing findings across surveys, the
      panel found that the period, definition of disability, treatment of the
      institutionalized population, and age standardizing of results were important to
      consider. The implications of the findings for policy, national survey efforts,
      and further research are discussed.

PMID- 15461009
TI  - Trends in socioeconomic inequalities in mortality in developing countries: the
      case of child survival in Sao Paulo, Brazil.
AB  - I examined trends in socioeconomic inequalities in under-five mortality for the
      state of Sao Paulo, Brazil, over a 21-year period from 1970 to 1991, during which
      much of the mortality transition unfolded. During this time, there was a decline
      in inequality in under-five mortality by household wealth but a substantial
      increase by mother's education. Improvements in infrastructure and economic
      development were associated with lower levels of socioeconomic inequality in
      under-five mortality. Mother's education emerged as the key factor underlying
      socioeconomic inequalities in under-five mortality even as levels of education
      for women increased and inequality in schooling fell.

PMID- 15461010
TI  - HIV status and union dissolution in sub-Saharan Africa: the case of Rakai,
      Uganda.
AB  - Little is known about the impact of HIV infection on the disruption of families
      through separation, divorce, and widowhood. Using life tables and multinomial
      logistic regression, this research examined the influence of HIV status on the
      risk of separation or divorce and widowhood among women in Rakai, Uganda. The
      multivariate results revealed that dissolution is more common among HIV-infected
      women and that infected women in HIV-discordant couples are especially likely to
      face separation or divorce than women in other HIV-status couples. These results
      highlight women's vulnerability to the social impact of HIV infection and the
      importance of dyadic studies of the disruption of unions.

PMID- 15461011
TI  - Orphans in Africa: parental death, poverty, and school enrollment.
AB  - We examine the impact of orphanhood on children's school enrollment in 10 sub
      Saharan African countries. Although poorer children in Africa are less likely to
      attend school, the lower enrollment of orphans is not accounted for solely by
      their poverty. We find that orphans are less likely to be enrolled than are
      nonorphans with whom they live. Consistent with Hamilton's rule, the theory that
      the closeness of biological ties governs altruistic behavior, outcomes for
      orphans depend on the relatedness of orphans to their household heads. The lower
      enrollment of orphans is largely explained by the greater tendency of orphans to
      live with distant relatives or unrelated caregivers.

PMID- 15461012
TI  - Pregnancy-related dropouts and gender inequality in education: a life-table
      approach and application to Cameroon.
AB  - In this study, I used a life-table approach to estimate how much hypothetical
      reductions in pregnancy-related dropouts would help close the gender gap in
      educational attainment. Using the schooling histories of 6,686 pupils, I
      partitioned Cameroon's gender gap in education into "pregnancy-related" and "non
      pregnancy-related" components and simulated the impact of reductions in pregnancy
      related dropouts on this gap. The results suggest that such reductions would have
      substantial payoffs in this setting, but payoffs would be the greatest where
      societies also address gender inequities before puberty and outside the realm of
      pregnancy. Reductions in pregnancy-related dropouts complement but do not replace
      efforts to reduce gender discrimination in schooling. Recent data from
      Demographic and Health Surveys should make it possible to extend this analysis to
      other countries.

PMID- 15461013
TI  - Pervasive Muslim-Hindu fertility differences in India.
AB  - Using the 1993 Indian Family and Health Survey, we examined Muslim-Hindu
      differences in (1) the parity-specific intent to have another child and (2) given
      a stated intent for no more children, reports of the current use of
      contraceptives. We found that Muslims are much more likely than Hindus to intend
      to have additional children and, among those who do not want more children,
      Muslims are much less likely than Hindus to use contraceptives. These findings
      are robust to model specification and pervasive across the states of India. This
      national study provides the context within which local studies should be enmeshed
      and begs for general (as opposed to place-specific) explanations for these
      pervasive differences.

PMID- 15461014
TI  - Birth month, school graduation, and the timing of births and marriages.
AB  - We investigated the timing of fertility and marriage in Sweden using exogenous
      variation in the age at school graduation that results from differences in birth
      month. Our analysis found that the difference of 11 months in the age at leaving
      school between women who were born in two consecutive months, December and
      January, implies a delay in the age at first birth of 4.9 months. This effect of
      delayed graduation also persists for the timing of second births and first
      marriages, but it does not affect completed fertility or the overall probability
      of marriage before age 45. These results suggest the existence of a relatively
      rigid sequencing of demographic events in early adulthood, and the age at
      graduation from school emerges as an important factor in determining the timing-
      but not the quantum--of familyformation. In addition, these effects point to a
      potentially important influence of social age, defined by an individual's school
      cohort, instead of biological age. The relevance of social age is likely due to
      social interactions and peer-group influences exerted by individuals who are in
      the same school cohort but are not necessarily of the same age.

PMID- 15461015
TI  - Effects of child health on parents' relationship status.
AB  - We used data from the Fragile Families and Child Wellbeing Study to estimate the
      effect of a child's poor health on the presence of thefather. We investigated
      whether parents lived in the same household 12-18 months after the child's birth
      and whether their relationships changed along a continuum (married, cohabiting,
      romantically involved, friends, or not involved) during the same period. We found
      that within this short period, having a child with poor health decreased the
      probability that the parents lived together by 10 percentage points. It also
      increased the probability that their relationship status moved in the direction
      of less involvement by 6 percentage points. These results indicate that
      children's health and family structure jointly shape children's long-term health
      and economic trajectories.

PMID- 15461016
TI  - Housing and wealth inequality: racial-ethnic differences in home equity in the
      United States.
AB  - In our study, we took a first step toward broadening our understanding of the
      sources of both housing and wealth inequality by studying differences in housing
      equity among blacks, Hispanics, Asians, and non-Hispanic whites in the United
      States. Using data from the American Housing Survey, we found substantial and
      significant gaps in housing equity for blacks and Hispanics (but not for Asians)
      compared with whites, even after we controlled for a wide range of locational,
      life-cycle, socioeconomic, family, immigrant, and mortgage characteristics.
      Furthermore, the payoffs to many factors are notably weaker for minority than for
      white households. This finding is especially consistent across groups for the
      effects of age, socioeconomic status, and housing-market value. Blacks and
      Hispanics also uniformly receive less benefit from mortgage and housing
      characteristics than do whites. These findings lend credence to the burgeoning
      stratification perspective on wealth and housing inequality that acknowledges the
      importance of broader social and institutional processes of racial-ethnic
      stratification that advantage some groups, whites in this case, over others.

PMID- 15461017
TI  - Attitudes and behaviors with regards to androgenic anabolic steroids among male
      adolescents in a county of Sweden.
AB  - This study investigates attitudes toward androgenic anabolic steroids among male
      adolescents who have used anabolics compared with those who have not. A cross
      sectional survey was performed in the year 2000 in all secondary schools in the
      county of Halland on the west coast of Sweden. An anonymous multiple-choice
      questionnaire was distributed to all classes with 14-, 16-, and 18-year-old male
      adolescents. The response rate was 92.7% (n=4049). Those who admitted having used
      androgenic anabolic steroids differed in several ways from those who had not.
      Fewer believed androgenic anabolic steroids to be harmful (OR=0.15, 95% CI 0.08
      0.30) and more believed that girls preferred boys with large muscles (OR=6.1, 95%
      CI 3.4-11.0). They trained more often at gyms (OR=5.6, 95% CI 3.0-10.6), drank
      more alcohol (OR=4.2, 95% CI 2.0-9.1), and had used narcotic drugs more often
      (OR=15.3, 95% CI 8.5-27.5) than the other male adolescents. More immigrants than
      native-born adolescents had used anabolics (OR=4.2, 95% CI 2.2-7.9). Attitudes
      toward anabolics differ between users and nonusers. These aspects may be
      beneficial to focus on as one part of a more complex intervention program in
      order to change these attitudes and decrease the misuse of androgenic anabolic
      steroids.

PMID- 15461018
TI  - Individual and environmental factors related to quitting heroin injection.
AB  - This study examines the relationship between individual-level and the certain
      neighborhood characteristics with drug use cessation among a sample of long-term
      inner-city heroin injectors in Baltimore, Maryland. The data were derived from
      baseline and first follow-up visits of SHIELD, a larger HIV prevention
      intervention study targeting members of the drug-using community. The survey
      instrument was interviewer-administered and ascertained sociodemographics, drug
      use history, and sexual and drug risk behaviors. The data were collected between
      August 1997 and March 1999. The current study was limited to participants with a
      median age of 41 years old. 27.5% (n=53) reported quitting drug use at follow-up.
      Compared with those who quit, participants who continued (n=147) were close to
      five times as likely to buy drugs in the neighborhoods in which they lived, 80%
      less likely to have used drugs in a shooting gallery in the past 6 months, and
      close to five times more likely to have used drugs in outside places. Controlling
      for other factors, enrollment in drug user treatment programs or attending self
      help groups were not significantly associated with drug use cessation. This study
      points to the importance of examining specific environmental factors in relation
      to quitting drug use. Research is needed to further articulate the types and
      characteristics of physical environments that are related to and could be
      intervened in promoting sustainable drug cessation.

PMID- 15461019
TI  - Association among outcomes in a naturalistic statewide assessment of substance
      user treatment.
AB  - Substance user treatment outcome measurement is important for research and policy
      questions, yet little literature has addressed the relationships among outcome
      measures of treatment success. Ideally, treatment outcomes would correlate to at
      least a moderate degree. The Iowa Department of Public health requires substance
      user treatment programs receiving public funds to provide client information.
      Demographic information, "substance abuse" history, current use, arrests, and
      hospitalizations were ascertained at admission and a 6-month follow-up for 1374
      clients (from January 1999 to December 2000). Abstinence, arrests, and
      hospitalizations were good outcome measures of substance user treatment success.
      Reduction in frequency of use was negatively associated with arrests, substance
      use-related hospitalizations, and increased income. Full-time employment at
      follow-up produced different results depending on the client's sex. However, all
      associations among outcomes were modest. Specificity may be reasonable in some
      instances; however, other situations might require a broad-spectrum approach that
      ideally would produce a wide range of benefits.

PMID- 15461020
TI  - Educating treatment professionals about addiction science research: demographics
      of knowledge and belief changes.
AB  - Communication of accurate, objective, and timely scientific information to
      treatment professionals is important--especially in the "drug abuse" and
      addiction field where misinformation and a lack of exposure to new information
      are common. The purpose of this study was to assess knowledge and belief changes
      that accompanied educational workshops (3 or 6 hr-long) on addiction science
      targeted to treatment professionals (N=1403) given in the United States and
      Puerto Rico between July 2000 and August 2001. Each workshop covered three main
      concepts: (1) terms and definitions; (2) basic neurochemistry of addiction; and
      (3) how new neurobiological knowledge will affect the treatment of addictions in
      the future. Analysis of variance was used to compare mean pretest to posttest
      change scores among levels of four independent variables: gender, age,
      occupation/position, and race/ethnicity. Workshop participants achieved a
      significant improvement in knowledge about addiction with younger groups
      achieving greater gains. Participants' beliefs shifted in the desired direction.
      Significant differences in belief shifts occurred among occupational and gender
      groups, but not among race/ethnicity or age groups. There was also a consistent
      change in the policy belief subscale that related to how strongly the audience
      members believed research on addiction was important. We conclude that addiction
      science education provided to treatment professionals can increase their
      knowledge and change their beliefs about the causes of addictions. In addition,
      the workshop participants form a base of constituents who are likely to support
      greater addiction research funding.

PMID- 15461021
TI  - Values and identity: the meaning of work for injection drug users involved in
      volunteer HIV prevention outreach.
AB  - Most HIV behavioral interventions provide participants with preventive
      information emphasizing how not to behave, and have neglected to provide
      attractive and feasible alternatives to risky behavior. Interventions that
      emphasize cultural strengths may have more powerful effects and may help remove
      the stigma of HIV, which has hampered prevention efforts among African American
      communities. Starting in 1997, the SHIELD (Self-Help in Eliminating Life
      Threatening Diseases) intervention trained injection drug users (N=250) to
      conduct risk reduction outreach education among their peers. Many participants
      saw their outreach as "work," which gave them a sense of meaning and purpose and
      motivated them to make other positive changes in their lives.

PMID- 15461022
TI  - Responding to substance use problems in Nigeria: the role of civil society
      organizations.
AB  - This descriptive study assesses the role of nongovernmental organizations (NGOs)
      in drug demand reduction (DDR) in Nigeria. Sixty-two respondents, representing 45
      organizations, participated in the survey in 2001. Most respondents were people
      with university education, and many were trained in health-related fields. A
      large majority (84%) were active in prevention work and 63% of them were engaged
      in research. Survey respondents reported that they were faced with many
      challenges in their work as DDR practitioners. These included poor funding or
      lack of it and inadequate information on drugs. Many also expressed the need for
      drug policy reforms in the country and an interest in further training in
      different areas of DDR. This article argues that a well-coordinated civil society
      participation is necessary in the control of drug problems in Nigeria. This goal
      can only be achieved in an environment where drug policy strikes a reasonable
      balance between supply and demand reduction efforts and, consequently, where
      support for DDR is seen as an integral part of drug control initiatives.

PMID- 15461023
TI  - [Japanese physicians'attitude for utilization of social support services for
      persons with intellectual disabilities].
AB  - We assessed physicians'attitude for the utilization of social (medical,
      educational, and financial) support services for persons with intellectual
      disabilities supplied by the Japanese government. A total of 113 physicians
      specializing in pediatric neurology answered our mail-in questionnaire. Medical
      care benefits for psychiatric outpatients and short-time stay were the most
      common services utilized. Whereas most physicians used various public support
      services regardless of their experience and affiliations, the selection of
      services by an individual physician correlated with the number and state of
      patients they usually cared. Physicians were less familiar with the services
      regarding residential or community care and advocacy. Knowledge of the
      specialists on each service will enrich assistance appropriate to the life styles
      of each patient with intellectual disabilities.

PMID- 15461024
TI  - [Sympathetic skin response and emotional changes of visual stimuli].
AB  - We studied sympathetic skin response (SSR) to visual emotional stimuli in 11
      normal children and 13 normal adults. The arousal and valence levels of original
      pictures were previously assessed by 20 normal children and adults. SSR
      appearance ratio tended to be high for pictures with high arousal and those with
      either high or low valence, and was higher in children than in adults. The
      response for pictures with high arousal and low valence was different between
      children and adults. These pictures were classified into 2 groups; one consisted
      of disgusting creatures such as worms and roaches, and another of violent scenes,
      symbolizing physiological and social unpleasure, respectively. In children, SSRs
      were evoked with the same ratio for these two groups of pictures. In adults,
      however, SSRs for social unpleasure pictures were evoked with a significantly
      higher ratio compared to those for physiological ones. These results indicate
      that children are more susceptible to emotional stimuli and that this
      susceptibility diminishes with development, suggesting the association between
      emotional signal and moral development.

PMID- 15461025
TI  - [Long-term follow-up of a case of eyelid myoclonia with absences].
AB  - We reported a case of eyelid myoclonia with absences treated for 10 years.
      Seizures of eyelid myoclonia accompanied by absence, precipitated by sunlight,
      began at the age of 4 years and disappeared at the age of 11 years. Non
      convulsive status epilepticus, occurring shortly after awakening, began at the
      age of 10 years and have occurred intermittently until the age of 18 years. While
      generalized EEG abnormalities disappeared after initiation of treatment, the
      patient still had occipital spikes on interictal EEG at the age of 18 years,
      suggesting occipital hyperexcitability as the basis of photosensitivity. Along
      with poor drug compliance due to her living apart from her parents, it was
      difficult to completely suppress non-convulsive status epilepticus, posing
      serious concern in her adult life.

PMID- 15461026
TI  - [Identification of ictal foci by EEG and MR apparent diffusion coefficient map in
      a case of human herpesvirus 6-associated encephalopathy].
AB  - We report here a 1-year-old boy with human herpesvirus 6 (HHV 6) -associated
      encephalopathy. On the 3rd day of fever, he had a generalized tonic seizure
      followed by mild disturbance of consciousness, which recovered completely the
      next day. Two days later, he had skin rash of exanthema subitum, and his
      consciousness declined frequently. EEG demonstrated rhythmic wave bursts
      originating from central areas bilaterally, followed by a generalized spike-and
      wave complex which was associated with disturbed consciousness. We made the
      diagnosis of a status of complex partial seizures. Because the focal discharge on
      ictal EEG, MRI was performed. In the subcortical white matter of the frontal
      parietal lobes, there were high signals on diffusion-weighted MRI, the apparent
      diffusion coefficient of which was much lower than that of normal controls. The
      affected areas soon disappeared with improvement of clinical symptoms. The
      transient MRI findings may indicate reversible cytotoxic brain edema. He showed
      no neurological sequelae as yet.

PMID- 15461027
TI  - [Two cases of adult Down syndrome treated with selective serotonin re-uptake
      inhibitor for behavior disorders].
AB  - Adult patients with Down syndrome show psychological symptoms and early senility.
      Improving their environment and dealing with their complaints and stress should
      first address their behavioral problems, such as self-injury, depression,
      aggression and outbursts. Pharmacological treatment may also be tried for
      behavioral disorders. Individuals with Down syndrome demonstrate neurotransmitter
      changes such as the loss of acetylcholine, norepinephrine, and serotonin (5-HT)
      with increasing age. Selective serotonin re-uptake inhibitor (SSRI) is effective
      for depression and panic disorders. We report here the effect of SSRI in two
      adult male patients with Down syndrome, 35 and 47 years of age. Self-injury in
      one case and aggression and outbursts in another improved after 1 week of
      fluvoxamine treatment, suggesting the effects of SSRI for behavioral disorders of
      adult Down syndrome.

PMID- 15461028
TI  - [Serial MEG change in a boy with Landau-Kleffner syndrome].
AB  - We report a 7-year-old boy with Landau-Kleffner syndrome (LKS), with emphasis on
      the effect of therapy and serial MEG. The equivalent current dipoles (ECDs) of
      spike discharges accumulated in the bilateral Heschl gyri, predominantly on the
      right. Although spike discharges on the scalp EEGs disappeared by treatment with
      clonazepam and sodium valproate, the auditory agnosia did not improve.
      Therapeutic trials with conventional antiepileptic drugs were unsuccessful. A
      high-dose corticosteroid was effective, with disappearance of ECDs, appearance of
      auditory evoked fields (AEF) in the bilateral Heschl gyri on MEG, and improvement
      of behavioral problems and amelioration of acquired aphasia. The clinical course
      of this patient suggests that MEG findings are useful not only in making precise
      diagnosis of LKS but also in assessing and predicting the effects of treatment.

PMID- 15461029
TI  - [The head MRI by fluid attenuated inversion recovery (FLAIR) was useful for
      diagnosis in the patient with post influenza vaccinal acute disseminated
      encephalomyelitis (ADEM)].
AB  - A 6-year-old, previously healthy boy developed ataxia and muscle weakness, 16
      days after influenza vaccination. The CSF showed an elevated level of myelin
      basic protein, pleocytosis and negative influenza virus isolation. The head MRI
      revealed an extensive high intensity area in the deep white matter, which was
      more clearly defined on FLAIR images. The diagnosis of post influenza vaccinal
      ADEM was made, and he was successfully treated by steroid pulse therapy with a
      monophasic course and favorable outcome.

PMID- 15461030
TI  - [Case of dentatorubral-pallidoluysian atrophy with onset of psychomotor
      retardation in infancy].
AB  - We report a patient with dentatorubral-pallidoluysian atrophy (DRPLA). She
      developed normally until the age of 6 month, when she could sit by herself.
      However, her psychomotor development was subsequently slow with gradual
      appearance of equilibrium disturbances and involuntary movements such as
      polymyoclonia and chorea. Her development deteriorated after myoclonic seizures
      developed at 4.5 years of age. Electroencephalograms showed semi-continuous
      bursts of diffuse irregular spike-wave complexes and MRI of the brain showed
      atrophy of the cerebellum and brainstem, and high signal intensities in the
      posterior periventricular triangle portion on T2-weighted images. Gene analysis
      performed at the age of 6 years revealed an expanded CAG repeat (17/74) at the
      DRPLA locus. The CAG repeat size was larger in this case than in cases of the
      adult and juvenile types with later onset, suggesting a correlation between
      repeat length and age at onset. Genetic examination of the family members was not
      performed because of her mother's fear and emotional confusion.

PMID- 15461031
TI  - [Case of severe motor and intellectual disabilities presenting with partial
      central diabetes insipidus triggered by infection].
AB  - We report a 42-year-old woman with severe motor and intellectual disabilities
      (SMID) who showed partial central diabetes insipidus during severe pneumonia.
      Serum sodium levels were previously within the upper normal range from 140 to 147
      mEq/L. During pneumonia, however, serum sodium rose rapidly to reach 185 mEq/L.
      The daily urinary volume exceeded the daily intake of water. Nasal administration
      of 1-desamino-8-D-arginine vasopressin (DDAVP) reduced the daily urinary volume
      and the serum sodium level to normal ranges. Consequently, we diagnosed her as
      having central diabetes insipidus (DI). She required a smaller dose of DDAVP (2.5
      microg/day) than usual DI (5-15 microg/day) to maintain normal urinary volume and
      the serum sodium level for seven months. After the nasal administration of DDAVP
      was discontinued, the serum sodium levels again returned to within the upper
      normal range. A water deprivation study demonstrated poor elevation of both
      plasma antidiuretic hormone (ADH) level (range, 0.5-2.0 pg/ml) and urine
      osmolarity (peak level, 552 mOsm/kgH2O) despite the elevation of plasma
      osomolarity, suggesting latent partial central DI. Water balance and serum
      electrolyte levels should be closely monitored in cases of SMID.

PMID- 15461032
TI  - [Usefulness of flexible bronchoscopy for aspiration of foods into the
      tracheobronchial trees in 2 patients with severe motor and intellectual
      disabilities].
AB  - Two patients with severe motor and intellectual disabilities who suffered from
      acute asphyxia and respiratory failure due to aspiration of foods into the
      tracheobronchial trees were reported. Numerous food particles were found in the
      tracheobronchial trees of both the patients. One patient showed recurrent
      atelectasis at various sites. After oral intubation, flexible bronchoscopy could
      successfully remove food particles from the tracheobronchial trees in both the
      patients without any complications. A rigid bronchoscope is usually recommended
      for removal of foreign bodies from the airways in children. However, it is
      difficult to use in patients with severe motor and intellectual disabilities,
      because their airway may show deformation or the aspirated foods may enter the
      peripheral bronchi. Our cases suggest that flexible bronchoscopy can be useful
      for removing foreign bodies from the tracheobronchial trees in neurologically
      handicapped patients for whom rigid bronchoscopy can not be applied.

PMID- 15461033
TI  - [Hemorheology and physiological function--factors influencing blood viscosity].

PMID- 15461034
TI  - Leadership in action: creating a change in practice.
AB  - Change is common and important in improving patient outcomes in the current
      healthcare market. Because of the tremendous increase in credible research and
      publication of research findings, clinicians now use evidence-based findings to
      guide their practice. The rapid changes in the healthcare environment require
      effective leaders that can implement change strategies to improve patient
      outcomes. Evidence has shown that clinicians may have difficulty integrating new
      knowledge into clinical practice. The advanced practice nurse (APN) equipped with
      advanced clinical knowledge and knowledge of the change process is perfectly
      situated in the healthcare setting to be an agent of change. This article focuses
      on the specific steps of the change process APNs can use to effect change in
      practice in their institutions. An example from the author's own clinical
      practice in implementing an intensive insulin drip protocol is outlined. The key
      elements important in successful development and implementation of a change in
      practice are presented. By improving the understanding of the change process,
      APNs as change agents can meet the challenge of leading the way to change in
      their clinical setting.

PMID- 15461035
TI  - Using mediation techniques to manage conflict and create healthy work
      environments.
AB  - Healthcare organizations must find ways for managing conflict and developing
      effective working relationships to create healthy work environments. The effects
      of unresolved conflict on clinical outcomes, staff retention, and the financial
      health of the organization lead to many unnecessary costs that divert resources
      from clinical care. The complexity of delivering critical care services makes
      conflict resolution difficult. Developing collaborative working relationships
      helps to manage conflict in complex environments. Working relationships are based
      on the ability to deal with differences. Dealing with differences requires skill
      development and techniques for balancing interests and communicating effectively.
      Techniques used by mediators are effective for resolving disputes and developing
      working relationships. With practice, these techniques are easily transferable to
      the clinical setting. Listening for understanding, reframing, elevating the
      definition of the problem, and forming clear agreements can foster working
      relationships, decrease the level of conflict, and create healthy work
      environments that benefit patients and professionals.

PMID- 15461036
TI  - Power: an application to the nursing image and advanced practice.
AB  - When asked to put a mental picture to the word nurse, the image people see is
      often far removed from the image nurses wish to project. Many see nurses as the
      handmaidens to physicians, wearing white caps and stockings, and surrendering
      their chairs to physicians. Others see unflattering images from the media.
      Nursing's tarnished image is partially responsible for a perception of oppression
      in nursing. Much of nursing's image problem relates to how nurses perceive and
      use power. Regardless of how nurses perceive power, it is through power that
      advanced practice nurses (APNs) will be acknowledged as members of a profession
      versus an occupation. With a better understanding of power, APNs may be able to
      improve their use of power to advance the profession. This article presents and
      discusses power through a review of the literature in order to better understand
      the term as it applies to advanced practice nursing.

PMID- 15461037
TI  - Mentoring matters: creating, connecting, empowering.
AB  - In the current chaotic healthcare environment, growth and development of nursing
      staff is essential to maintain quality outcomes. The purpose of this article is
      to highlight the concept of mentoring, explain the benefits of mentoring in
      fostering the development of novice nurses, and present a primer for how advanced
      practice nurses could implement a mentoring relationship. A three-step mentoring
      process of reflecting, reframing, and resolving is described with examples of
      implementation of these steps.

PMID- 15461038
TI  - Troubled units: creating change.
AB  - Your unit may be in trouble. Are conversations among team members authentic or do
      real conversations happen in the hallways after the meeting? Are staff afraid of
      voicing their disagreements for fear of being labeled, while other team members
      complacently agree to a consensus, then go off and work from their own agenda?
      Some units have fallen into the habit of disrespectful communication and uncaring
      behaviors toward team members. The impact this has on staff, units, and
      organizations can be deleterious. More importantly, these behaviors impact the
      quality of patient care a unit is able to provide. Fostering teamwork must be a
      top priority for leaders. In a healthy team, differences and conflict exist, but
      they are acknowledged and dealt with openly. Creating change in a troubled unit
      is not a fast fix, but rather needs a well-devised plan. This article describes
      how leaders can seek out appropriate resources, develop strategies, and intervene
      to create a healthy, professional work environment.

PMID- 15461039
TI  - Heat loss and continuous renal replacement therapy.
AB  - Because of the devastating consequences of thermal imbalance, it is imperative
      that nurses understand these concepts and apply them to the daily care of their
      patients. Heat loss, heat conservation, and heat generation interplay to maintain
      the narrow range that is considered optimal for human cellular function. These
      concepts factor into patients who are critically ill but are especially important
      for patients undergoing continuous renal replacement therapy. Many of these types
      of dialysis expose the individual patient's blood to room temperature dialysate
      via an extracorporeal circuit 24-hours a day, sometimes for several weeks at a
      time. Critical care and advanced practice nurses must understand the interplay of
      the processes of heat loss, conservation, and heat generation to ensure patients
      undergoing this therapy achieve maximum benefit with the fewest complications
      possible.

PMID- 15461040
TI  - Malignant hyperthermia: pathophysiology, clinical presentation, and treatment.
AB  - Malignant hyperthermia (MH) was first described as an inherited highly lethal
      disorder in 1960. There has since been significant progress in the clinical
      management, identification of MH susceptible (MHS) persons, and understanding of
      the underlying pathophysiology. When patients are known to be MHS prior to
      surgery, an MH episode can easily be avoided by the use of safe nontriggering
      anesthetic agents. Current MH mortality is <10%, but many experts believe this
      can be significantly reduced by improved MH preparedness. MH is triggered in
      humans by an MH triggering anesthetic agent, which causes the release of calcium
      from the sarcoplastic reticulum of the skeletal muscle cell at an uncontrolled
      rate resulting in a hypermetabolic state. Recent molecular genetic studies have
      shown that MH is related to an abnormal ryanodine receptor that controls the
      release of calcium from the sarcoplastic reticulum. This article reviews the
      current understanding of the pathophysiology, diagnosis, clinical presentation,
      and treatment of MH.

PMID- 15461041
TI  - The effects of drugs on thermoregulation.
AB  - Body temperature is a balance of the hypothalamic set point, neurotransmitter
      action, generation of body heat, and dissipation of heat. Drugs affect body
      temperature by different mechanisms. Antipyretics lower body temperature when the
      body's thermoregulatory set point has been raised by endogenous or exogenous
      pyrogens. The use of antipyretics may be unnecessary or may interfere with the
      body's resistance to infection, mask an important sign of illness, or cause
      adverse drug effects. Drugs may cause increased body temperature in five ways:
      altered thermoregulatory mechanisms, drug administration-related fever, fever
      from the pharmacologic action of the drug, idiosyncratic reactions, and
      hypersensitivity reactions. Certain drugs cause hypothermia by depression of the
      thermoregulatory set point or prevention of heat conservation. By affecting the
      balance of thermoregulatory neurotransmitters, drugs may prevent the signs and
      symptoms of hot flashes.

PMID- 15461042
TI  - Can there be a standard for temperature measurement in the pediatric intensive
      care unit?
AB  - Temperature measurement is a commonly used assessment parameter when caring for
      the critically ill child. Interpreting the temperature measurement mode and what
      constitutes clinically significant thermal instability are poorly defined. Thus,
      decisions made regarding patient management based on temperature measurement can
      be challenging for caregivers. Infants and children have unique physioanatomic
      considerations that impact maintaining thermoregulation. Numerous routes for
      taking temperature measurements are described including the oral, axillary,
      tympanic (aural), rectal, skin, urinary bladder, pulmonary artery, esophageal,
      nasopharyngeal, supralingual (pacifier), and temporal-artery. Numerous studies on
      temperature measurement have been conducted on children of various ages using a
      variety of thermometers and routes in both the inpatient and outpatient setting.
      Although there are limited studies reported on the critically ill child, research
      data pertinent to the critically ill child from subjects in the neonatal
      intensive care unit, pediatric intensive care unit, operating room, and inpatient
      units are summarized.

PMID- 15461043
TI  - Shivering in acutely ill vulnerable populations.
AB  - The hazards of thermoregulatory shivering in the critically ill are often
      overlooked by caregivers. Shivering may accompany heat loss from bathing,
      dressing, transport, and many therapeutic activities. Febrile shivering is common
      during chills of fever, blood product transfusions, administration of antigenic
      drugs, and chemotherapy. Many patients are at risk for shivering and its negative
      consequences that increase oxygen expenditure and cardiorespiratory effort.
      Learning how underlying thermoregulatory mechanisms are involved in shivering
      clarifies how temperature gradients and environmental stimuli induce the
      shivering response. Knowledge of the anatomical progression of shivering equips
      the nurse to recognize or prevent this energy-consuming response. This article
      discusses measures to prevent shivering as well as evidence-based interventions
      to manage shivering during fever, aggressive cooling, and postoperative recovery.
      Detailed information is presented on assessment and documentation of the extent
      and severity of shivering.

PMID- 15461044
TI  - Heat stroke: a comprehensive review.
AB  - Heat stroke (HS) is a serious and potentially life-threatening condition defined
      as a core body temperature >40.6 degrees C. Two forms of HS are recognized,
      classic heat stroke, usually occurring in very young or elderly persons, and
      exertional heat stroke, more common in physically active individuals. An elevated
      body temperature and neurologic dysfunction are necessary but not sufficient to
      diagnose HS. Associated clinical manifestations such as extreme fatigue; hot dry
      skin or heavy perspiration; nausea; vomiting; diarrhea; disorientation to person,
      place, or time; dizziness; uncoordinated movements; and reddened face are
      frequently observed. Potential complications related to severe HS are acute renal
      failure, disseminated intravascular coagulation, rhabdomyolysis, acute
      respiratory distress syndrome, acid-base disorders, and electrolyte disturbances.
      Long-term neurologic sequelae (varying degrees of irreversible brain injury)
      occur in approximately 20% of patients. The prognosis is optimal when HS is
      diagnosed early and management with cooling measures and fluid resuscitation and
      electrolyte replacement begins promptly. The prognosis is poorest when treatment
      is delayed >2 hours.

PMID- 15461045
TI  - [Sleep disorders in elderly].
AB  - Insomnia affects 20% of the adult population in western countries and its
      prevalence increases with age. There is a controversy regarding the origin of
      sleep disorders in elderly. Are they only due to a senile process of sleep
      functioning or due to other associated comorbidities? Considering the objective
      assessment of sleep in elderly (by polysomnography), it has been shown an
      increasing sleep latency, decreasing total sleep time and sleep efficiency, a
      lower percentage of slow wave sleep. The circadian clock is also modified by age
      with phase advance and a decreased amplitude of the circadian rhythms. The most
      relevant comorbidities found in older people are: sleep apneas, restless leg
      syndrome, psychiatric disorders (anxiety and depression) and the use of drugs.

PMID- 15461046
TI  - [Heat-related disorders. Anticipating the consequences of excessive heat before
      the emergency arises].

PMID- 15461047
TI  - [The heat wave of August 2003: what happened?].
AB  - A heat wave of exceptional intensity occurred in France in August 2003, 2003 was
      the warmest of the last 53 years in terms of minimal, maximal and average
      temperatures, and in terms of duration. In addition, high temperatures and
      sunshine, causing the emission of pollutants, significantly increased the
      atmospheric ozone level. Some epidemiological studies were rapidly implemented
      during the month of August in order to asses the health impact of this heat wave.
      Excess mortality was estimated at about 14 800 additional deaths. This is
      equivalent to a total mortality increase of 60% between August 1st and 20th, 2003
      (Inserm survey). Almost the whole country was concerned by this excess-mortality,
      even in locations where the number of very hot days remained low. Excess
      mortality clearly increased with the duration of extreme temperatures. These
      studies also described the features of heat-related deaths. They showed that the
      death toll was at its highest among seniors and suggested that less autonomous or
      disabled or mentally ill people were more vulnerable. So, they provided essential
      information for the setting up of an early warning system in conjunction with
      emergency departments. The public health impact of the Summer 2003 heat wave in
      various European countries was also assessed. Different heat waves in term of
      intensity had occurred at different times in many countries with each time deaths
      in excess. But, it does seem that France was the most affected country. However,
      implementation of standardized methods of data collection through all countries
      is necessary to afford further comparisons. Collaborative studies will be
      conducted in this way. After theses first descriptive studies, further etiologic
      studies on risk factors and heat-related deaths were launched and are now in
      progress. Considering the health impact of the heat wave, national health
      authorities decided to launch an Heat Wave National Plan including a provisional
      Heat Watch Warning System (HWWS) for 2004. Developed in collaboration with Meteo
      France, this HWWS is based upon an analysis of historical daily mortality data
      and meteorological indicators in 14 French cities in order to define the best
      indicators and triggers. The public health impact of the heat wave of August 2003
      was major. This exceptional event raises questions about anticipating phenomena
      which are difficult to predict. The collaborative efforts which were developed
      and the group of actions and studies which were implemented in a context of
      emergency are now useful for the setting up of early warning strategies and thus
      efficient prevention.

PMID- 15461048
TI  - [Disorders caused by prolonged exposure to heat].
AB  - France has suffered last summer an unprecedented heat wave that led to an
      exceptional short-term surge of mortality. Cumulative deaths between August 1st
      to 14th are estimated at 14,800. Epidemiological studies carried out by the
      Institute de Veille Sanitaire will show the circumstances and risk factors
      leading to heat-related pathologies. A literature review already shows the
      principles of prevention, the circumstances of occurrences during similar past
      heat waves, the risk factors and the principles of treatment. Prolonged exposure
      to heat can be the initial cause of death, mainly in the elderly. The subject
      thus dies of an overload of his natural defenses, unable to preserve his thermal
      homeostasis. This is then a heat shock that reaches the central nervous system.
      Heat shocks could kill every second patient and leads to severe neurological
      sequel. During a heat wave, high temperatures can also trigger or worsen other
      illnesses or be responsible for other so called heat-related syndromes. It is
      crucially important to identify subjects at risk, situations of risk, and
      preventive measures, knowing that heat shock leads 25% of patients to develop
      multi-organ failure, even when appropriately treated.

PMID- 15461049
TI  - [Persons at risk in a heat wave].

PMID- 15461050
TI  - [Prevention of health risks linked to extreme heat].
AB  - The prevention of the health risks linked to the excess of heat comprises 5 axes:
      the sensitisation of fragile persons, families and health personnel to the danger
      that extreme heat represents; informing and educating about the measures to take
      before summer and during the scorching heat, identification of persons at risk,
      protecting, surveilling and alerting them. Two messages predominate: refresh
      oneself at least 2 hours per day in a cool place (less than 26 degrees C), and
      drink before being thirsty and beyond the thirst. The efficacity of the measures
      depend upon the level of general awareness when faced with the health risk that
      is associated with extreme heat.

PMID- 15461051
TI  - [Good utilization of medications during a heat wave].

PMID- 15461052
TI  - [You and your treatment in case of a heat wave].

PMID- 15461053
TI  - [National ranking examination for medical graduates: contextual elements and
      analysis].

PMID- 15461054
TI  - [Naso-sinusoidal infections in children and adults. Part I: Children].

PMID- 15461055
TI  - [Skin eruptions in children].

PMID- 15461056
TI  - [Septicemia].

PMID- 15461057
TI  - [Surveillance of patients in plaster of Paris].

PMID- 15461058
TI  - [Problems caused by genetic diseases. Part 3: Chromosomal disorders: trisomy 21].

PMID- 15461059
TI  - [Eyelid pathology].

PMID- 15461060
TI  - [Assisted reproductive technologies. Clinical and biological aspects and ethical
      considerations].

PMID- 15461061
TI  - [Scorching heat and days of extreme heat: heat and health by Hippocrates in the
      XVIII century].

PMID- 15461062
TI  - Mechanisms of anti-ischemic action of prostaglandin E1 in peripheral arterial
      occlusive disease.
AB  - The mechanisms of anti-ischemic effects of PGE1 in patients with peripheral
      arterial occlusive disease (PAD) are probably complex and clearly not limited to
      a direct vasodilator action. In addition to the known effects on blood flow,
      viscosity, fibrinolysis and platelet aggregation, the compound also inhibits
      monocyte and neutrophil function, suggesting that PGE1 will also have anti
      inflammatory effects. Recent research has detected additional actions of PGE1 and
      prostacyclin analogs which might be relevant to its clinical efficacy. This
      includes inhibition of expression of adhesion molecules (E-selectin, ICAM-1, and
      VCAM-1), release of inflammatory cytokines (TNFalpha, MCP-1), matrix components
      and generation and release of growth factors (CYR61, CTGF). These actions may
      also contribute to the long-term effects of PGE1, particularly in more advanced
      stages of PAD. Gene-expression experiments with chemically stable prostacyclins
      and PGE1 suggest that several genes in vascular smooth muscle cells and
      fibroblasts are modified by prostaglandins at the transcriptional level. This
      includes TNFalpha-induced VCAM expression in vascular smooth muscle cells which
      appears to be inhibited via the prostaglandin EP2 receptor as well as IL-1
      induced expression of the type-1 collagen gene in fibroblasts. Thus, regulation
      of gene transcription by PGE1 may contribute to tissue protection in critical
      ischemia of the lower limbs.

PMID- 15461063
TI  - Media remodeling--the result of stent induced media necrosis and repair.
AB  - BACKGROUND: Stents have been introduced clinically to help maintaining the
      patency of the vascular lumen after balloon angioplasty. To ensure a sufficient
      lumen of the stented vessel, oversized stents are frequently used. However
      especially deployment of oversized stents may lead to mechanical injury of the
      intima and media of the vessel wall. The aim of the study was to characterize the
      vascular lesions and repair processes within the first 4 weeks after implantation
      of oversized stents in the rabbit carotid artery and thereby contribute to the
      understanding of vascular remodeling during stent implantation. METHODS:
      Oversized stents were implanted in the carotid artery of Chinchilla rabbits.
      Rabbits were sacrificed 3, 7, 14, and 28 days after stent implantation and a
      detailed histologic and immunohistochemical analysis was performed. RESULTS: The
      carotid artery was expanded by a factor of 1.3-1.5, leading to a constant
      dilatation of the vessel. The struts were deeply impressed in the vessel wall,
      resulting in a disruption of the intima, thrombus formation, media compression
      and segmental media necrosis. The necrotic media was repopulated by smooth muscle
      cells by day 7. In contrast to the intima lesions, necrotic areas of the media
      were not invaded by an inflammatory infiltrate. Formation of neointima,
      characterized by a confluent layer of endothelial cells and deposition
      collagenfibers started in close vicinity of the struts. CONCLUSIONS: Being part
      of a high-pressure system, the arterial vessel apparently adapts to constant
      dilatation. Deployment of oversized stents caused intima disruption, media
      necrosis of varying degree and constant dilatation of the vessel wall. Necrosis
      and repopulation of smooth muscle cells of the media took place within the first
      4 weeks, leading to the speculation whether the repopulating SMC are more
      resistant to the constant pressure.

PMID- 15461064
TI  - Effects of intravenous prostaglandin E1 on arterial compliance: a randomized
      controlled trial.
AB  - BACKGROUND: Prostanoids are in widespread use for the treatment of critical limb
      ischemia and are suggested to improve arterial compliance. However, dose- and
      time-dependency of these drug effects are indeterminate. We investigated the
      influence of intravenous application of prostanoids on arterial compliance
      parameters in patients with critical limb ischemia due to peripheral artery
      disease (PAD). PATIENTS AND METHODS: We included 82 consecutive patients with PAD
      Fontaine stage III and IV in a patient-blinded, randomized controlled trial.
      Patients were randomly assigned to either single dose intravenous treatment with
      40 microg (n = 29) or 60 microg (n = 27) of Alprostadil (PGE1) in 250 ml 0.9%
      saline over 2 hours, or 250 ml 0.9% saline solution as a placebo group (n = 26).
      Large and small artery compliance was measured by peripheral pulse contour
      analysis at baseline, at one hour during intravenous infusion of Alprostadil,
      immediately after and 24 hours after the end of the infusion. For study purposes
      the patients received Alprostadil only once during the observation period of 2
      days. RESULTS: Large artery compliance, blood pressure, heart rate and cardiac
      output were unaffected by PGE1 administration irrespectively of drug-dosage or
      time interval. Small artery compliance increased at 1 hour during intravenous
      application of Alprostadil (40 microg Alprostadil p = 0.001; 60 microg
      Alprostadil p < 0.0001) compared to placebo and increased median +47% (IQR +5% to
      +100%) after administration of 40 microg Alprostadil and median +32% (IQR -11% to
      +88%) after 60 microg Alprostadil (p = 0.5). Immediately after the end of
      Alprostadil infusion small artery compliance decreased to baseline levels.
      CONCLUSIONS: Prostaglandin E1 causes a significant improvement of small artery
      compliance during the time of intravenous application. However, this effect
      rapidly diminishes after the end of administration and no dose-dependency between
      40 microg and 60 microg Alprostadil is observed.

PMID- 15461065
TI  - Meta-analysis of randomised controlled prostaglandin E1 studies in peripheral
      arterial occlusive disease stages III and IV.
AB  - BACKGROUND: The relevance of Prostaglandin El (PGE,) in the treatment of
      peripheral arterial occlusive disease stage III and IV was to be evaluated for
      the first time by a meta-analysis. PATIENTS AND METHODS: Altogether, 643 patients
      were analyzed from seven randomized, controlled PGE1 studies that were comparable
      with regard to patient selection, study design and endpoints. Of these, only
      placebo-controlled studies (n = 254) were included in the formal meta-analysis
      using the method of DerSimonian and Laird. Additionally, the response rate and
      the rate of adverse events were determined for the pooled groups of all studies.
      RESULTS: At the end of treatment, PGE1 showed a significantly better response
      (ulcer healing and/or pain reduction) as compared to placebo (47.8% for PGE1, vs.
      25.2% for placebo, p = 0.0294). A significant difference in favor of PGE1 was
      also seen for the combined endpoint "major amputation or death" after 6-month
      follow-up (22.6% for PGE1 vs. 36.2% for placebo, p = 0.0150). The response rate
      (ulcer healing and/or pain relief) of the pooled treatment groups was 60.2% for
      PGE1, 25.2% for placebo, and 53.6% for iloprost. The adverse events rate of the
      pooled treatment groups showed good tolerability for PGE, with a rate of 39.6% in
      comparison to 73.9% for iloprost and 15.4% for placebo. CONCLUSION: For patients
      with peripheral arterial occlusive disease stage III or IV not eligible for
      arterial reconstruction, PGE1 therapy not only has significant beneficial effects
      over placebo on ulcer healing and pain relief but also increases the rate of
      patients surviving with both legs after 6-months follow-up.

PMID- 15461066
TI  - Treatment costs and quality of life of patients with peripheral arterial
      occlusive disease--the German perspective.
AB  - BACKGROUND: To objectify the debate about the restricted resources of the health
      system, examinations about the treatment costs and quality of life implications
      of different illnesses are necessary. The aims of the examination were the
      quantification of costs that are caused by a patient with PAD per year and the
      determination of the quality of life. PATIENTS AND METHODS: 280 patients (mean
      66.6 years) in Fontaine stages II to IV were included in the study to determine
      their treatment costs for the year 2001 retrospectively from patient records.
      Health-related quality of life was recorded through the standardized
      questionnaires PAVK-86, SF-36 and EQ-5D. RESULTS: A patient with PAD in stage Ila
      costs on average 1792.45 Euros, in stage IIb 2551.28 Euros, in stage III 4356.48
      Euros and in stage IV 6225.89 Euros. The costs of the in-hospital treatment
      dominated the total result on average with 44.4% of the direct costs. Further
      cost factors were the drugs with 33.4%, the out-patient medical treatment with
      9.9%, the expenditures for care with 6.7%, rehabilitation with 3.6% and adjuvants
      with a share of 1.9%. The indirect costs played a subordinate role with 9.67% of
      the total costs. The quality of life was clearly restricted in all stages of the
      PAD. The quality of life especially was strongly decreased from the Fontaine
      stage IIb on. The problems were mainly in the areas of the physicalfunctions and
      pain. CONCLUSION: The study showed that the treatment of patients with PAD is
      very cost-intensive and that patients have to suffer from a considerable loss of
      quality of life.

PMID- 15461067
TI  - Frequency of non-vascular accompanying diseases in patients with peripheral
      arterial disease.
AB  - BACKGROUND: Since there are so far no relevant figures on the frequency of non
      vascular associated diseases in patients with peripheral arterial disease (PAD),
      an analysis was carried out to determine how frequently co-morbidity is found in
      such patients. PATIENTS AND METHODS: In the course of a retrospective analysis,
      1693 patients (55.4% men, 44.6% women/average 68.6years) with peripheral arterial
      diseases (PAD) of Fontaine stage II to IV were examined to find out how often
      cardiopulmonary, gastrointestinal, haematological, endocrinological,
      neurological, orthopaedic, urological-nephrological, psychiatric diseases and
      tumours were seen. RESULT: Coronary ischaemic heart disease was present in 63.1%
      of the cases, heart failure existed in 20.7%, hypertension in 57.9%, endocrine
      and metabolic diseases in 60.4%, gastrointestinal diseases in 14.8%, pulmonary
      diseases in 14.5%, psychological and behavioural deficiencies in 16.2%,
      orthopaedic diseases in 21.6%, haematological diseases in 9.0%, urological
      diseases in 16.9%, chronic renal insufficiency in 7.3% and malignant tumours in
      5.8%. CONCLUSIONS: The frequency of non-vascular comorbidity in patients with PAD
      necessitates systematic interdisciplinary diagnosis prior to any therapy decision
      to take into account the patient's associated diseases, life expectancy and
      current quality of life.

PMID- 15461068
TI  - Incidence of varicose veins in Finland.
AB  - BACKGROUND: Incidence of varicose veins in the population is unknown. The study
      aimed at estimating the incidence of varicose veins in complete cohorts of 40-60
      year-olds in a general population. PATIENTS AND METHODS: The study was conducted
      in the city of Tampere, Finland. A validated questionnaire (with 93% sensitivity
      and 92% specificity) was used in a general population of 6874 individuals (aged
      40, 50 or 60). Initially, 3065 of them had no varicose veins and 78% were
      followed-up for 5 years. RESULTS: 157 individuals reported new varicose veins
      during the follow-up. The overall incidence was 13.5 per 1000 person years (8.5
      for men and 19.2 for women). Female sex was an independent and statistically
      significant risk indicator of varicose veins (adjusted odds ratio, OR 2.4). The
      incidence was significantly higher at the age of 50-55 years (OR 1.6). Higher
      body mass index seemed to be related to higher risk of new varicose veins (OR 1.2
      1.8), but the association failed to reach statistical significance. The level of
      education did not affect the incidence. CONCLUSIONS: New varicose veins appear
      also in the middle-aged population, and the rate is linked with the female
      gender, especially at the beginning of the 6th decade.

PMID- 15461069
TI  - Species-dependent premature degradation of absorbable suture materials caused by
      infection--impact on the choice of thread in vascular surgery.
AB  - BACKGROUND: In case of infection after vascular reconstruction, preference is
      often given to absorbable suture material with the aim of preventing persistence
      of infection. We have investigated the functional deficit of absorbable sutures
      on incubation with various different bacteria. MATERIAL AND METHODS: Four suture
      materials Dexon bicolor, Vicryl, Maxon and PDS II--were placed in contact with
      reference bacterial cultures (Staphylococcus aureus, Pseudomonas aeroginosa, E.
      coli, coagulase-negative staphylococci and Proteus mirabilis). The bacteria were
      incubated for 7 days at 37 degrees C, together with the suture material. A
      logarithmic phase (Group A) and a static phase (Group B) were simulated. The
      linear tensile strength (LTS) of the suture material was measured (Instron
      Tensiometer). RESULTS: In the case of Staphylococcus aureus, a significant
      decrease in LTS was established for Dexon bicolor (group A: 31%, group B: 22%),
      and Vicryl (53% and 43%), but not for the monofilament threads. With regard to
      the other bacteria, a considerably more dramatic effect was observed: in both
      groups the braided sutures had completely disintegrated after 7 days. The
      monofilament sutures also revealed a significant loss of function (Maxon: 88%,
      PDS II 66%). CONCLUSIONS: The absorbable sutures revealed a premature, species
      dependent loss of function due to the presence of the bacteria. On the basis of
      our results, the use of absorbable threads for vessel sutures in case of
      infection cannot be recommended, with the exception of monofilament material in a
      monocultural Staphylococcus aureus infection.

PMID- 15461070
TI  - Time for a new classification of femoral artery aneurysm?
AB  - It has been over 30 years now since the original classification of femoral artery
      aneurysms by Darning and Cutler to type 1 and 2. We have demonstrated in a case
      report that it is time for amendment of this classification. Isolated profunda
      aneurysm do exist as separate entity, and they can be managed by complete
      exclusion from the circulation provided the presence of patent superficial
      femoral artery and good runoff circulation, without any ill effects.

PMID- 15461071
TI  - Frostbite in a mountaineer.
AB  - Cold injury is an objective danger in mountain climbing as well as in many
      outdoor sports. With increasing number of people practising so-called extreme
      tourisms physicians can be confronted with frostbite. Thus we present a case of
      frostbite in a 35 year-old female mountaineer. She took part at a demanding high
      alpine trekking tour in the Himalayan-area requesting well trained mountaineers
      experienced in ice- and securing-techniques and good physical condition. At day
      12, when the group reached the top of the Parchamo (Nepal, 6273 m), she developed
      frostbite at all toes leading to amputation finally. Risk factors, prognosis and
      options for initial treatment are discussed.

PMID- 15461072
TI  - Special issue on information theoretic learning.

PMID- 15461073
TI  - A new criterion using information gain for action selection strategy in
      reinforcement learning.
AB  - In this paper, we regard the sequence of returns as outputs from a parametric
      compound source. Utilizing the fact that the coding rate of the source shows the
      amount of information about the return, we describe l-learning algorithms based
      on the predictive coding idea for estimating an expected information gain
      concerning future information and give a convergence proof of the information
      gain. Using the information gain, we propose the ratio w of return loss to
      information gain as a new criterion to be used in probabilistic action-selection
      strategies. In experimental results, we found that our w-based strategy performs
      well compared with the conventional Q-based strategy.

PMID- 15461074
TI  - Variational learning and bits-back coding: an information-theoretic view to
      Bayesian learning.
AB  - The bits-back coding first introduced by Wallace in 1990 and later by Hinton and
      van Camp in 1993 provides an interesting link between Bayesian learning and
      information-theoretic minimum-description-length (MDL) learning approaches. The
      bits-back coding allows interpreting the cost function used in the variational
      Bayesian method called ensemble learning as a code length in addition to the
      Bayesian view of misfit of the posterior approximation and a lower bound of model
      evidence. Combining these two viewpoints provides interesting insights to the
      learning process and the functions of different parts of the model. In this
      paper, the problem of variational Bayesian learning of hierarchical latent
      variable models is used to demonstrate the benefits of the two views. The code
      length interpretation provides new views to many parts of the problem such as
      model comparison and pruning and helps explain many phenomena occurring in
      learning.

PMID- 15461075
TI  - Adaptive probabilistic neural networks for pattern classification in time-varying
      environment.
AB  - In this paper, we propose a new class of probabilistic neural networks (PNNs)
      working in nonstationary environment. The novelty is summarized as follows: 1) We
      formulate the problem of pattern classification in nonstationary environment as
      the prediction problem and design a probabilistic neural network to classify
      patterns having time-varying probability distributions. We note that the problem
      of pattern classification in the nonstationary case is closely connected with the
      problem of prediction because on the basis of a learning sequence of the length
      n, a pattern in the moment n + k, k > or = 1 should be classified. 2) We present,
      for the first time in literature, definitions of optimality of PNNs in time
      varying environment. Moreover, we prove that our PNNs asymptotically approach the
      Bayes-optimal (time-varying) decision surface. 3) We investigate the speed of
      convergence of constructed PNNs. 4) We design in detail PNNs based on Parzen
      kernels and multivariate Hermite series.

PMID- 15461076
TI  - Gradient-based manipulation of nonparametric entropy estimates.
AB  - This paper derives a family of differential learning rules that optimize the
      Shannon entropy at the output of an adaptive system via kernel density
      estimation. In contrast to parametric formulations of entropy, this nonparametric
      approach assumes no particular functional form of the output density. We address
      problems associated with quantized data and finite sample size, and implement
      efficient maximum likelihood techniques for optimizing the regularizer. We also
      develop a normalized entropy estimate that is invariant with respect to affine
      transformations, facilitating optimization of the shape, rather than the scale,
      of the output density. Kernel density estimates are smooth and differentiable;
      this makes the derived entropy estimates amenable to manipulation by gradient
      descent. The resulting weight updates are surprisingly simple and efficient
      learning rules that operate on pairs of input samples. They can be tuned for data
      limited or memory-limited situations, or modified to give a fully online
      implementation.

PMID- 15461077
TI  - Probabilistic sequential independent components analysis.
AB  - Under-complete models, which derive lower dimensional representations of input
      data, are valuable in domains in which the number of input dimensions is very
      large, such as data consisting of a temporal sequence of images. This paper
      presents the under-complete product of experts (UPoE), where each expert models a
      one-dimensional projection of the data. Maximum-likelihood learning rules for
      this model constitute a tractable and exact algorithm for learning under-complete
      independent components. The learning rules for this model coincide with
      approximate learning rules proposed earlier for under-complete independent
      component analysis (UICA) models. This paper also derives an efficient sequential
      learning algorithm from this model and discusses its relationship to sequential
      independent component analysis (ICA), projection pursuit density estimation, and
      feature induction algorithms for additive random field models. This paper
      demonstrates the efficacy of these novel algorithms on high-dimensional
      continuous datasets.

PMID- 15461078
TI  - Entropy-based kernel mixture modeling for topographic map formation.
AB  - A new information-theoretic learning algorithm for kernel-based topographic map
      formation is introduced. In the one-dimensional case, the algorithm is aimed at
      uniformizing the cumulative distribution of the kernel mixture densities by
      maximizing its differential entropy. A nonparametric differential entropy
      estimator is used on which normalized gradient ascent is performed. Both
      differentiable and nondifferentiable kernels are in principle supported, such as
      Gaussian and rectangular (on/off) kernels. The relation is shown with joint
      entropy maximization of the kernel outputs. The learning algorithm's performance
      is assessed and compared with the theoretically optimal performance. A fixed
      point rule is derived for the case of heterogeneous kernel mixtures. Finally, an
      extension of the algorithm to the multidimensional case is suggested.

PMID- 15461079
TI  - From blind signal extraction to blind instantaneous signal separation: criteria,
      algorithms, and stability.
AB  - This paper reports a study on the problem of the blind simultaneous extraction of
      specific groups of independent components from a linear mixture. This paper first
      presents a general overview and unification of several information theoretic
      criteria for the extraction of a single independent component. Then, our
      contribution fills the theoretical gap that exists between extraction and
      separation by presenting tools that extend these criteria to allow the
      simultaneous blind extraction of subsets with an arbitrary number of independent
      components. In addition, we analyze a family of learning algorithms based on
      Stiefel manifolds and the natural gradient ascent, present the nonlinear optimal
      activations (score) functions, and provide new or extended local stability
      conditions. Finally, we illustrate the performance and features of the proposed
      approach by computer-simulation experiments.

PMID- 15461080
TI  - Advanced search algorithms for information-theoretic learning with kernel-based
      estimators.
AB  - Recent publications have proposed various information-theoretic learning (ITL)
      criteria based on Renyi's quadratic entropy with nonparametric kernel-based
      density estimation as alternative performance metrics for both supervised and
      unsupervised adaptive system training. These metrics, based on entropy and mutual
      information, take into account higher order statistics unlike the mean-square
      error (MSE) criterion. The drawback of these information-based metrics is the
      increased computational complexity, which underscores the importance of efficient
      training algorithms. In this paper, we examine familiar advanced-parameter search
      algorithms and propose modifications to allow training of systems with these ITL
      criteria. The well known algorithms tailored here for ITL include various
      improved gradient-descent methods, conjugate gradient approaches, and the
      Levenberg-Marquardt (LM) algorithm. Sample problems and metrics are presented to
      illustrate the computational efficiency attained by employing the proposed
      algorithms.

PMID- 15461081
TI  - Advances on BYY harmony learning: information theoretic perspective, generalized
      projection geometry, and independent factor autodetermination.
AB  - The nature of Bayesian Ying-Yang harmony learning is reexamined from an
      information theoretic perspective. Not only its ability for model selection and
      regularization is explained with new insights, but also discussions are made on
      its relations and differences from the studies of minimum description length
      (MDL), Bayesian approach, the bit-back based MDL, Akaike information criterion
      (AIC), maximum likelihood, information geometry, Helmholtz machines, and
      variational approximation. Moreover, a generalized projection geometry is
      introduced for further understanding such a new mechanism. Furthermore, new
      algorithms are also developed for implementing Gaussian factor analysis (FA) and
      non-Gaussian factor analysis (NFA) such that selecting appropriate factors is
      automatically made during parameter learning.

PMID- 15461082
TI  - Learning mixture models with the regularized latent maximum entropy principle.
AB  - This paper presents a new approach to estimating mixture models based on a recent
      inference principle we have proposed: the latent maximum entropy principle (LME).
      LME is different from Jaynes' maximum entropy principle, standard maximum
      likelihood, and maximum aposteriori probability estimation. We demonstrate the
      LME principle by deriving new algorithms for mixture model estimation, and show
      how robust new variants of the expectation maximization (EM) algorithm can be
      developed. We show that a regularized version of LME (RLME), is effective at
      estimating mixture models. It generally yields better results than plain LME,
      which in turn is often better than maximum likelihood and maximum a posterior
      estimation, particularly when inferring latent variable models from small amounts
      of data.

PMID- 15461083
TI  - A new information processing measure for adaptive complex systems.
AB  - This paper presents an implementation-independent measure of the amount of
      information processing performed by (part of) an adaptive system which depends on
      the goal to be performed by the overall system. This new measure gives rise to a
      theoretical framework under which several classical supervised and unsupervised
      learning algorithms fall and, additionally, new efficient learning algorithms can
      be derived. In the context of neural networks, the framework of information
      theory strives to design neurally inspired structures from which complex
      functionality should emerge. Yet, classical measures of information have not
      taken an explicit account of some of the fundamental concepts in brain theory and
      neural computation, namely that optimal coding depends on the specific task(s) to
      be solved by the system and that goal orientedness also depends on extracting
      relevant information from the environment to be able to affect it in the desired
      way. We present a new information processing measure that takes into account both
      the extraction of relevant information and the reduction of spurious information
      for the task to be solved by the system. This measure is implementation
      independent and therefore can be used to analyze and design different adaptive
      systems. Specifically, we show its application for learning perceptrons, decision
      trees and linear autoencoders.

PMID- 15461084
TI  - A negentropy minimization approach to adaptive equalization for digital
      communication systems.
AB  - In this paper, we introduce and investigate a new adaptive equalization method
      based on minimizing approximate negentropy of the estimation error for a finite
      length equalizer. We consider an approximate negentropy using nonpolynomial
      expansions of the estimation error as a new performance criterion to improve
      performance of a linear equalizer based on minimizing minimum mean squared error
      (MMSE). Negentropy includes higher order statistical information and its
      minimization provides improved converge, performance and accuracy compared to
      traditional methods such as MMSE in terms of bit error rate (BER). The proposed
      negentropy minimization (NEGMIN) equalizer has two kinds of solutions, the MMSE
      solution and the other one, depending on the ratio of the normalization
      parameters. The NEGMIN equalizer has best BER performance when the ratio of the
      normalization parameters is properly adjusted to maximize the output
      power(variance) of the NEGMIN equalizer. Simulation experiments show that BER
      performance of the NEGMIN equalizer with the other solution than the MMSE one has
      similar characteristics to the adaptive minimum bit error rate (AMBER) equalizer.
      The main advantage of the proposed equalizer is that it needs significantly fewer
      training symbols than the AMBER equalizer. Furthermore, the proposed equalizer is
      more robust to nonlinear distortions than the MMSE equalizer.

PMID- 15461086
TI  - President's editorial--Some thoughts on the future of scientific publishing.

PMID- 15461085
TI  - Feature selection in MLPs and SVMs based on maximum output information.
AB  - This paper presents feature selection algorithms for multilayer perceptrons
      (MLPs) and multiclass support vector machines (SVMs), using mutual information
      between class labels and classifier outputs, as an objective function. This
      objective function involves inexpensive computation of information measures only
      on discrete variables; provides immunity to prior class probabilities; and
      brackets the probability of error of the classifier. The maximum output
      information (MOI) algorithms employ this function for feature subset selection by
      greedy elimination and directed search. The output of the MOI algorithms is a
      feature subset of user-defined size and an associated trained classifier
      (MLP/SVM). These algorithms compare favorably with a number of other methods in
      terms of performance on various artificial and real-world data sets.

PMID- 15461087
TI  - Cremation weights in east Tennessee.
AB  - In spite of increasing number of cremations in the U.S., little is known about
      weights of cremated remains. This research was undertaken in order to add to the
      limited literature on cremains weights and to explore variation. Weights of
      cremated remains were obtained from the East Tennessee Crematorium. The sample
      consists of 151 males and 155 females. Age, sex, and race were obtained for each
      individual. Males are about 1000 g heavier than females. Both sexes lose weight
      with age, but females lose weight at about twice the rate of males. East
      Tennessee cremation weights were compared with those from Florida reported by
      Warren and Maples, and those from Southern California reported by Sonek. East
      Tennessee results were also compared with an earlier study on ash weight of
      anatomical human skeletons carried out by Trotter and Hixon. East Tennessee
      cremations weigh about 500 g more than the samples from Florida and California,
      and about the same as the earlier anatomical samples. We hypothesize that
      variation reflects variation in body weight and activity. This variation must be
      taken into account when cremation weights are at issue.

PMID- 15461088
TI  - Reconsidering the auricular surface as an indicator of age at death.
AB  - Using standards established by Lovejoy et al. to estimate age at death from
      auricular surface morphology, 266 individuals of documented age, sex, and
      ancestry from the Terry and Bass Donated Collections were scored. Analysis of
      covariance (ANCOVA) indicates that for the factors that could be controlled, age
      is the sole influence on auricular surface morphology. Ancestry and sex had no
      significant effect on auricular phase expression. No evidence of secular changes
      was detected when comparing the Terry Collection (early 20th century) to the Bass
      Collection (later 20th century). Pearson correlations reveal that several of the
      subcomponents of the auricular surface (superior and inferior demifaces, left and
      right sides, transverse organization, texture) correspond with age equally well,
      although a combined scoring of all features performs slightly better than any one
      indicator taken alone. Not surprisingly, only 33% of the sample was correctly
      aged when using the 5-year age ranges provided by Lovejoy et al., suggesting that
      the published ranges are much too narrow to be used in forensic contexts. To
      assess the variation in age per phase, standard descriptive statistics and error
      ranges were calculated and can be employed by forensic anthropologists when
      estimating the age of an unidentified decedent. Because the mean ages of some of
      the eight phases did not differ significantly from one another, a modified six
      phase system is presented. The auricular surface performs as well as any other
      single skeletal indicator of adult age. This research suggests that a
      statistically-informed approach should be taken in order to fully understand the
      drawbacks and limitations of any aging method.

PMID- 15461089
TI  - Fetal visceral maturation: a useful contribution to gestational age estimation in
      human fetuses.
AB  - With regard to the law, estimating fetal age is essential to assess viability
      (after 20 weeks according to the WHO) and the proposed methods generally use long
      bone measurements. Here, we evaluated the accuracy of soft tissue maturational
      stage and compared it with long bone measurements. First, eight kinds of tissues
      or organs from 448 fetuses with known medical history were studied
      (macroscopically or histologically). We clearly demonstrated that adrenal glands
      and skin were very good age indicators, because some characteristics appeared
      only after 20 weeks. We established a linear regression with a 95% confidence
      interval of +/- 2.9 weeks. Second, we applied our original formula using femur
      measurement and we combined soft tissues and bones in a multiparametric
      regression. The confidence interval was reduced to +/- 2.5 weeks. We conclude
      that the pathologist must use both histological and anthropometric data to
      determine fetal age as accurately as possible.

PMID- 15461090
TI  - Interpretation of postmortem change in cadavers in Spain.
AB  - Estimating time since death is especially difficult in the examination of poorly
      preserved cadavers and depends on the experience of the examiner and comparison
      with previously documented cases showing similar characteristics. The present
      study reports on information obtained over the past ten years through the work of
      the Laboratorio de Antropologia y Odontologia Forense (LAF) of the Instituto
      Anatomico Forense de Madrid, Spain, in particular evaluating how the type of
      fracture influences postmortem change. From the original 225 forensic cases
      examined between 1992 and 2002 in the LAF, a sample of 29 cases were selected
      from various regions of the Spanish mainland. A data collection protocol was
      established to reflect factors which the existing specialized literature,
      documenting the relation existing in the sample analyzed between time since death
      and the extent of postmortem change, which in the environments examined are
      distributed into the following phases: Phase 1 (putrefaction): one week to one
      month on the surface and two months in water. Phase 2 (initial skeletonization):
      two months on the surface and five to six months in water. Phase 3 (advanced
      skeltonization): six months to 1.5 years on the surface and 2.5 years buried.
      Phase 4 (complete skeletonization): about one year on the surface and three years
      buried. This paper also provide useful information on the impact of carrion
      insect activity, location, climate, seasonality, and predator.

PMID- 15461091
TI  - Use of solid-phase double-antibody radioimmunoassay to identify species from
      small skeletal fragments.
AB  - Protein radioimmunoassay (pRIA) offers the potential to identify species in small
      skeletal fragments submitted as forensic evidence. The technique consists of
      protein extraction followed by a solid-phase double-antibody radioimmunoassay
      using controls of antisera (raised in rabbits) and radioactive (iodine-125)
      antibody of rabbit gamma globulin (produced in donkeys). Species determination
      results from evaluation of radioactivity uptake. To demonstrate the potential of
      this technique, six known bone samples (three human and three nonhuman, including
      one from a deer [Odocoileus virginianus]) were submitted for blind analysis. pRIA
      correctly distinguished the human from the nonhuman samples. Using 200 mg or less
      of each sample, species of the deer specimen was identified correctly, given the
      choices of cow, deer, dog, goat, and pig.

PMID- 15461092
TI  - Effects of processing techniques on the forensic DNA analysis of human skeletal
      remains.
AB  - Human remains processed by forensic anthropologists may potentially be used for
      genetic analysis. Therefore, the condition of the deoxyribonucleic acid (DNA) in
      processed remains may become an issue for future analysis. Processing techniques
      employed by anthropologists are highly variable and scanning electron microscopy
      reveals significant alterations to the bone surface depending upon the technique
      used. Such damage to the bone indicates differences may exist in quality and
      quantity of DNA extracted. This study assessed how five processing procedures
      used by major forensic anthropology laboratories around the country affects the
      amounts of DNA extracted from human rib bones and the subsequent DNA analysis.
      The DNA was analyzed using the short tandem repeat (STR) locus CSF1PO and
      amelogenin. The findings indicate processing procedures used by forensic
      anthropologists do not adversely affect DNA analysis but prolonged exposure to
      heat during processing may decrease the yield of information from the DNA.

PMID- 15461093
TI  - Improved method for the detection of TATP after explosion.
AB  - TATP in post explosion exhibits was reported earlier to be best recovered from
      vapor phase. A typical procedure includes its adsorption on Amberlite XAD-7,
      elution with acetonitrile and analysis by GC/MS. In this work, improved recovery
      of TATP from the vapor phase was achieved by SPME using PDMS/DVB fiber and
      immediate sampling to GC/MS. The recovery of TATP by SPME was compared with
      headspace and with adsorption on Amberlite XAD-7 by spiking onto filter paper put
      in a 100 mL beaker. The limit of detection of TATP was 6.4 ng in these
      conditions, few orders magnitude more than in the other tested methods. Recovery
      of TATP in the presence of various solvents was also studied. Acetone, water, and
      mixtures of water:alcohols (1:1) were found to reduce the recovery of TATP. Using
      SPME, TATP has been identified in dozens of post-explosion cases.

PMID- 15461094
TI  - Enhanced kinship analysis and STR-based DNA typing for human identification in
      mass fatality incidents: the Swissair flight 111 disaster.
AB  - A bioinformatic tool was developed to assist with the victim identification
      initiative that followed the Swissair Flight 111 disaster. Making use of short
      tandem repeat (STR) DNA typing data generated with AmpFlSTR Profiler Plus (PP)
      and AmpFlSTR COfiler(CO) kits, the software systematically compared each
      available STR genotype with every other genotype. The matching algorithm was
      based on the search for: (i) direct matches to genotypes derived from personal
      effects; and (ii) potential kinship associations between victims and next-of-kin,
      as measured by allele sharing at individual loci. The software greatly assisted
      parentage analysis by enabling kinship evaluation in situations where complete
      parentage trios were unavailable and, in some situations, with distantly related
      relatives. Exclusion of fortuitous kinship associations (FKA) was made possible
      through the recovery at the disaster site of at least one remains for every
      sought-after victim, and was incorporated into the kinship software. The data
      from the 13 combined STR loci produced 6 and 23 times fewer FKAs when compared
      with PP alone and AmpFlSTR Profiler (PR) alone, respectively. Identification
      leads or confirmations of identification were obtained for 218 victims for which
      DNA reference samples (personal effects and kin) had been submitted. Confirmation
      of an inferred kinship association was sought through frequency and likelihood
      calculations, as well as corroborative data from other identification modalities.
      The use of a simple, yet powerful, automated genotype comparison approach and the
      use of megaplexes with high power of discrimination (PD) values extended
      considerably the identification capabilities in the case of the Swissair
      disaster. The DNA typing identification modality proved to be a valuable
      component of the large arsenal of identification tools deployed in the aftermath
      of this disaster.

PMID- 15461095
TI  - Stable isotope ratios as a tool in microbial forensics--Part 1. Microbial
      isotopic composition as a function of growth medium.
AB  - The stable isotope ratios of a seized pathogen culture could potentially reveal
      information about the environment in which the agent was produced. In this paper
      we describe general relationships between stable isotopes of carbon, nitrogen,
      and hydrogen in bacteriological culture media and spores of Bacillus subtilis, an
      endospore-forming soil bacterium. In numerous media that varied both in nutrient
      composition and water stable isotope ratios, medium to spore enrichment in carbon
      isotopes was 0.3 +/- 2.0% per thousand (parts per thousand), and in nitrogen, 4.5
      +/- 0.7% per thousand. We achieved mass balance for the contribution of hydrogen
      isotopes from nutrients (70%) and water (30%) to spores in independent
      experiments by varying the isotope ratios of nutrients or water. A model was
      derived for predicting the isotope ratio values of spores from those in nutrients
      and water.

PMID- 15461096
TI  - Stable isotope ratios as a tool in microbial forensics--Part 2. Isotopic
      variation among different growth media as a tool for sourcing origins of
      bacterial cells or spores.
AB  - Since the anthrax attacks of 2001 the need for methods to trace the origins of
      microbial agents has become urgent. The stable isotope ratios of bacteria record
      information from both the nutrients and the water used to make their culture
      media and could potentially be used to provide information about their growth
      environment. We present a survey of carbon (C), nitrogen (N), and hydrogen (H)
      stable isotope ratios in 516 samples of bacteriological culture media. The
      observed variation was consistent with expected isotopic variation in the plant
      and animal products upon which the media are based. The variation is sufficient
      to translate into substantial isotope variation in cultures grown on different
      batches of media, and thus to allow investigators to determine whether seized
      media could have been used to produce seized bioweapons agents.

PMID- 15461097
TI  - Systematic analysis of stutter percentages and allele peak height and peak area
      ratios at heterozygous STR loci for forensic casework and database samples.
AB  - To assist the interpretation of STR DNA typing results from forensic casework
      samples containing mixtures, the range of heterozygous allele peak height and
      peak area ratios (HR) and stutter percentages (stutter %) for the loci comprised
      in the AmpFlSTR Profiler Plus (PP) kit were assessed on 468 database and 275
      casework single source samples. Stutter % medians were similar for database and
      casework samples, ranging from 2% to 7%. The upper limit of the stutter value
      range was 16%, calculated as median +3 SD, although lower locus-specific values
      could be used. HR medians were 93 +/- 6.5% for database samples, 88 +/- 12% for
      casework samples. For casework samples, the maximum signal imbalance noted was
      52%, calculated as median -3 SD. No significant difference was observed between
      peak height and peak area calculated values. This study shows the importance of
      selecting the proper reference database for the establishment of HR threshold
      values.

PMID- 15461098
TI  - Fingerprints' third dimension: the depth and shape of fingerprints penetration
      into paper--cross section examination by fluorescence microscopy.
AB  - In an attempt to maximize the yield of latent fingerprints from paper items, we
      conducted a study of a fundamental process between fingerprint deposits and
      paper. Fingerprint ridges have been observed in the cross section of paper by
      fluorescence microscopy. It was possible to see, for the first time, how residue
      from fingerprint ridges is embedded in paper. Undeveloped, latent fingerprints,
      as well as latent prints developed by the two fluorogenic reagents, DFO and 1,2
      indanedione, have been examined. The shape and depth of penetration of
      fingerprints vary with different types of paper. An inverse relationship between
      the smoothness of the paper and the penetration depth was observed: higher
      smoothness values result in lower depths of penetration. High quality prints
      appear to correlate with an optimal penetration depth-between 40 and 60 microns.

PMID- 15461099
TI  - Mitochondrial DNA heteroplasmy among hairs from single individuals.
AB  - A denaturing gradient gel electrophoresis (DGGE) assay was used to detect
      mitochondrial DNA (mtDNA) sequence heteroplasmy in 160 hairs from each of three
      individuals. The HV1 and HV2 heteroplasmic positions were then identified by
      sequencing. In several hairs, the heteroplasmic position was not evident by
      sequencing and dHPLC separation of the homoduplex/heteroduplex species was
      carried out with subsequent reamplification and sequencing to identify the site.
      The overall detection frequency of sequence heteroplasmy in these hairs was 5.8%
      (28/480) with DGGE and 4.4% (21/280) with sequencing. Sequence heteroplasmy of
      hair was observed even when the reference blood sample of the individual was
      homoplasmic. The heteroplasmic positions were not necessarily observed at sites
      where high rates of substitution have been reported. In two hairs, a complete
      single base change from the reference blood sample was observed with sequencing,
      while the heteroplasmic condition at that site in the hair was observed using
      DGGE. The DGGE results in such samples would serve as an aid in considering the
      possibility of match significance. In a forensic case, this situation would lead
      to the possibility of a failure to exclude rather than to be inconclusive.

PMID- 15461100
TI  - Aromatic content in medium range distillate products--Part I: an examination of
      various liquids.
AB  - Classification of ignitable liquids in accordance with voluntary consensus-based
      standards published by ASTM International has become increasingly specific,
      relying upon both the chemical composition and the boiling point range of
      submitted ignitable liquids. This classification system includes among others,
      specific classes for distillates and dearomatized distillates. In this study, a
      variety of medium-range ignitable liquids were analyzed by gas chromatography
      mass spectrometry. Several methods of data analysis were utilized to examine the
      relative aliphatic and aromatic contents in these liquids. Results show that
      commercially available products in the medium range exhibit a broad range of
      compositions with respect to the relative proportion of aliphatic and aromatic
      compounds and that some liquids may not be easily classified. This study
      demonstrates the importance of examining the proportion of aliphatics:aromatics
      for classifying such liquids and suggests guidelines for differentiating medium
      range distillates, dearomatized distillates, and blended products.

PMID- 15461101
TI  - Organic explosives analysis using on column-ion trap EI/NICI GC-MS with an
      external source.
AB  - In this study, a standard method by gas chromatography coupled with mass
      spectrometry (GC/MS) for the analysis of classical organic explosives was
      developed. This method was validated in the EI mode, based on the XPT 90-210
      standard method. Detection limits (LOD) and quantitation limits (LOQ) were both
      determined using electronic impact (EI) and negative ion chemical ionization
      (NICI) modes. These were compared and results showed that in the NICI mode,
      detection limits were lower than in the EI mode, thus NICI mode appeared to be
      the best way to analyze nitrate esters. Results of ion trap MS detection were
      then compared with those obtained in a previous study with single quadrupolar
      technology. Major ions that were obtained using ion trap MS detection in these
      two modes were reported.

PMID- 15461102
TI  - Matching and partially-matching DNA profiles.
AB  - The DNA profiles of two individuals can have 0, 1, or 2 pairs of alleles that are
      the same at each locus. These events may be called mismatches, partial matches or
      matches, respectively, and they have probabilities that depend on the population
      proportions of alleles as well as the population structure parameter theta. The
      observed and expected numbers of pairs of individuals with various numbers of
      matching or partially matching loci in FBI and Australian databases are found to
      be in good agreement provided theta is set equal to some small value greater than
      zero. The likelihood ratios for two individuals having a specified degree of
      relationship versus being unrelated also depend on the numbers of matching and
      partially matching loci, but even unrelated pairs of individuals can have
      likelihood ratios that support hypotheses of relatedness. Matching probabilities
      allow predictions to be made for the sizes of databases that are expected to
      contain a pair of individuals with high numbers of matching loci. It is very
      likely that two individuals with at least 9 matching loci among the 13 CODIS loci
      have already been typed.

PMID- 15461103
TI  - Fingerprint detection on counterfeit US dollar banknotes: the importance of
      preliminary paper examination.
AB  - Two seizures of counterfeit 100 US dollar bills related to the same indicative
      number were submitted for processing of latent fingerprints. On one group of
      notes, identifiable fingerprints could be detected by the routine application of
      amino acid reagents. In the second case, this technique gave no results, even on
      deliberately deposited prints. Fingerprints could be revealed, however, by
      cyanoacrylate fuming followed by magnetic powder. Comprehensive paper analysis
      showed that banknotes from both seizures differed remarkably by chemical
      composition as well as paper macroscopic properties. The difference in surface
      free energy (related to surface tension) of the banknotes in the two groups
      seemed to be the major factor responsible for the great variance in fingerprint
      detectability.

PMID- 15461104
TI  - Comparison of gasolines using gas chromatography-mass spectrometry and target ion
      response.
AB  - Gas chromatography-mass spectrometry was used to compare gasoline samples
      obtained from different sources based on the difference in amounts of certain
      components found in the headspace of gasoline using target response data. Many
      suspected arson cases involve comparing an ignitable liquid extracted from fire
      debris to a liquid found in a suspect's possession to determine if they could
      have had a common source. Various component ratios are proposed for determining
      if an unevaporated gasoline sample could have originated from the same source as
      an evaporated gasoline extracted from fire debris. Fifty and 75% evaporated
      gasoline samples were both found to contain similar ratios of certain components
      when compared with its unevaporated source gasoline. The results of the
      comparisons in this study demonstrate that for cases involving gasoline that has
      been evaporated up to 50% and extracted from pine, it is possible to eliminate
      comparison samples as originating from the same source. The results of the 75%
      comparisons suggest it may be possible to apply the same type of comparison to
      cases involving 75% evaporated gasoline.

PMID- 15461105
TI  - Sub-sampling and preparing forensic samples for pollen analysis.
AB  - The main forensic application of palynology is in providing associative evidence,
      assisting to prove or disprove a link between people and objects with places or
      with other people. Although identification and interpretation of pollen is a
      specialist job, sub-sampling and preparing pollen samples for analysis may be
      carried out by non-specialists. As few forensic laboratories have residing
      palynologists, laboratories may wish to reduce the cost of analysis or risk of
      contamination by doing their own sub-sampling and preparation. Presented is a
      practical guide for sub-sampling and preparing forensic samples for pollen
      analysis, providing a complete standard procedure for both the palynologist and
      non-specialist. Procedures for sub-sampling include a wide variety of materials
      commonly collected for forensic analysis (soil, clothing and other fabrics,
      footwear, twine and rope, firearms, granulated materials, plant and animal
      material, and illicit drugs), many of which palynologists will not be familiar
      with. Procedures for preparation of samples (pollen concentration) are presented
      as a detailed, step-by-step method. Minimizing the risks of laboratory and cross
      sample contamination during sub-sampling and preparation is emphasized.

PMID- 15461106
TI  - A case study on forensic polymer analysis by DIOS-MS: the suspect who gave us the
      SLIP.
AB  - New technology was used to identify traces of a commercial barrier/spermicide in
      evidence from a case of a man accused of rape of a minor. Examination of vaginal
      swabs performed by another laboratory had been negative for seminal fluid or
      other sources of DNA from the suspect and we were asked to examine the remaining
      swabs for any traces that might have originated from the commercial product.
      Encare consists of vaginal inserts having a suppository-like shape. They contain
      the spermicide, nonoxynol-9, in a matrix consisting of approximately two parts
      polyethylene glycol (PEG) 1000 to one part PEG 1450, plus minor inorganic
      components added to produce foaming. Portions of the cotton from vaginal swabs
      from the victim and penile swabs from the suspect were extracted with methanol
      and subsequently examined by desorption ionization on silicon time-of-flight mass
      spectrometry (DIOS TOF MS). Low levels of PEG in the same mass range as Encare
      were found on two separate vaginal swabs from the victim and one penile swab from
      the suspect. Subsequent to these findings, the suspect (through his attorneys)
      provided us with a sample of SLIP Plus, a commercial sexual lubricant that also
      contains nonoxynol-9. Traces of PEG in the same mass range as Encare were found
      in this sample, while no PEG was found in a sealed sample of SLIP Plus provided
      by the manufacturer. At trial the suspect's attorneys stipulated that their
      client had added some Encare to the SLIP Plus sample he had provided.

PMID- 15461107
TI  - The belated autopsy and identification of an eighteenth century naval hero--the
      saga of John Paul Jones.
AB  - John Paul Jones, the "Father of the American Navy," is known for the battletime
      assertion that he had "not yet begun to fight." His central role in a triumph of
      scientific forensic identification more than a century after his death is less
      known. John Paul Jones died in 1792 and was buried in Paris, France. The location
      of his grave was lost over time and a search for his corpse began in 1899.
      Remains matching his physical characteristics and circumstance of burial were
      discovered in 1905 and returned to the United States for a hero's burial. Some
      questioned the identification at the time and the major source of identifying
      information has since been shown to contain false information. The published
      forensic literature fails to address existing critiques of the identification. We
      provide a substantive analysis and conclude that the available evidence supports
      the identification of the unknown remains as those of John Paul Jones.

PMID- 15461108
TI  - The impact of anti-stalking training on front line service providers: using the
      anti-stalking training evaluation protocol (ASTEP).
AB  - The Anti-Stalking Training Evaluation Protocol (ASTEP) was developed to provide
      Safe Horizon, a large victim service provider, with an opportunity to evaluate
      and improve its anti-stalking training program. This report presents the results
      of this effort to measure Safe Horizon staff's knowledge and general perceptions
      about stalking, and to assess the impact of anti-stalking training on knowledge
      about the anti-stalking law, and stalking in general. Although these trainees
      appeared familiar with stalking issues, they were able to benefit from
      information about different types of stalkers and stalking, and about the legal
      options available to victims. The implication of the findings is that, if
      relatively well-informed staff members of a large victim services agency can
      benefit from training about stalking behavior, anti-stalking legislation and the
      needs of stalking victims, there is almost certainly a need for such training
      among a wider population of victim service providers, law enforcement
      professionals, and the general public.

PMID- 15461109
TI  - A calibrated gray scale for forensic ultraviolet photography.
AB  - The human eye is an important tool for observing evidence, and visual evidence in
      turn may be documented onto a photographic medium. The human eye is generally
      sensitive only to a narrow band of the electromagnetic spectrum from about 700 nm
      (red) to about 400 nm (violet/blue). It is possible to extend the range of
      radiations over which evidence may be documented by using the natural ultraviolet
      sensitivity of photographic films. However, photographing evidence with
      ultraviolet radiation ultimately involves presenting the information to subjects
      who may have no prior experience at viewing these wavelengths. This study shows
      that it is necessary to use a calibrated ultraviolet reflecting gray scale to
      allow meaningful interpretation of results.

PMID- 15461110
TI  - Dental maturity in South France: A comparison between Demirjian's method and
      polynomial functions.
AB  - The dental maturity of 1031 healthy southern French subjects aged between 2 and
      18 years was studied with dental panoramic tomograms. Demirjian's method based on
      seven and eight teeth has been used to determine maturity scores as a function of
      age and polynomial functions to determine age as a function of score. We give
      gender-specific tables of maturity scores and development graphs for each method.
      The goal of these methods is different because of the nature of the predictions.
      The percentiles give the dental maturity compared to a standard for a specific
      age, and polynomial functions give an age prediction with a confidence interval
      for age. The variations in dental maturity are specific to each population. Thus,
      the aim of this study is to give the dental maturity standards for southern
      French children and to compare both the efficiency and applicability of each
      method in several fields such as forensic sciences or dental health for the
      clinicians. The addition of the third molar increased the reliability and the
      capacity of prediction up to 18 years. The polynomial functions showed the best
      reliability (1.3% of misclassified) and the percentile methods the best accuracy
      (more or less 1.2 years, on average, between 2 and 18 years of age).

PMID- 15461111
TI  - The USS Iowa disaster: success of the forensic dental team.
AB  - The authors record the contributions of dentistry to the identification of the
      crew members who were in one of the most significant peacetime military accidents
      in U.S. Navy history-the April 1989 explosion in a gun turret on the battleship
      USS Iowa and the deaths of 47 U.S. Navy personnel. Dental identification was the
      primary means of identification for most because a very high percentage of the
      bodies were burned or fragmented. The dental-identification team's success was a
      direct result of its preparedness, its use of dental personnel with mass-disaster
      experience, and the overall excellent quality of the antemortem dental records.
      The dental-identification team's successful involvement in the USS Iowa tragedy
      was considered a model for success and therefore was instrumental in contributing
      to the development of the American Board of Forensic Odontology "Guidelines for
      the Development of a Disaster Dental Identification Team."

PMID- 15461112
TI  - Self-extraction of teeth involving gamma-hydroxybutyric acid.
AB  - A case involving self-extraction of teeth linked to the abuse of gamma
      hydroxybutyric acid (GHB) is reported. A 28-year-old woman and her 29-year-old
      boyfriend were discovered by paramedics following an extensive period of GHB use.
      The paramedics were alerted by a neighbor who had heard screaming from the house.
      On presentation to the accident and emergency department, it was noted that the
      female had 18 fresh extraction sockets visible intra-orally. At the scene, a
      mirror, a pair of pliers, and a bowl containing human teeth were found. Charges
      of assault were taken to the courts against the boyfriend who was subsequently
      acquitted. Odontological evidence centered on whether or not it was possible to
      self-extract the teeth using the pliers found. This case is the first to describe
      possible oral self-mutilation under the influence of GHB and odontologists should
      always consider self-injury as an explanation for intra- and perio-oral injuries
      of unknown origin.

PMID- 15461113
TI  - Estimation of caloric deficit in a fatal case of starvation resulting from child
      neglect.
AB  - We report the case of a 3-year-20-day-old girl who died of starvation as a result
      of severe neglect. Her body weight had been 12 kg 70 days before her death, but
      was only 5 kg at the time of autopsy. From information supplied by her parents to
      police, we calculated her daily caloric intake and estimated the factors for
      physical activity. The daily recommended dietary allowance for the victim was
      calculated from 700 kcal/ day x the appropriate factor for physical activity. In
      the absence of enough food, body fat (7.2 kcal/g body fat) and protein (4 kcal/g
      protein) would have been used to compensate until death. The calculated body
      weight at the time of death was around 5 kg. The statements of the parents
      therefore appear to be true.

PMID- 15461114
TI  - Postmortem analysis of anastomotic suture line disruption following carotid
      endarterectomy.
AB  - The tensile strength of a surgical suture is essential in maintaining the
      integrity of vascular anastomoses. While faulty operative technique and the
      loading strength of individual sutures have been implicated in spontaneous suture
      line disruptions, there has, to date, never been a published postmortem analysis
      of a suture that has known to have failed. We present the case of suture line
      disruption leading to fatal exsanguination in a 77-year-old man following carotid
      endarterectomy with a facial vein patch. Using both dissecting and scanning
      electron microscopy, we determined that surgical technique (an untied knot) was
      the cause of the suture line disruption. The removal of a broken or untied suture
      at surgery or at autopsy should not preclude proper analysis of the failed
      suture, because the results can have both medico-legal and public health
      implications.

PMID- 15461115
TI  - Homicidal cerebral artery aneurysm rupture.
AB  - When a normally natural mechanism of death is induced by physical injury or
      intense emotional stress, it is appropriate to rule the manner of death as
      something other than natural. When the case-specific circumstances are such that
      the death occurs as a result of the criminal activity of another person, it is
      acceptable to rule such deaths as homicides. Presented herein is a case of
      homicidal cerebral artery aneurysm rupture occuring in an intoxicated, 46-year
      old man who was punched in the face by another individual. The details of the
      case are presented, followed by a discussion of the controversies that exist when
      dealing with such cases. Guidelines for investigating similar deaths are
      presented, with emphasis on the timing of the trauma in relation to onset of
      symptoms due to aneurysm rupture.

PMID- 15461116
TI  - A research review of public figure threats, approaches, attacks, and
      assassinations in the United States.
AB  - The authors review extant research on threats, approaches, attacks, and
      assassinations of public figures in the United States. Despite the limited number
      of studies, data exist concerning: 1) threatening letters and approaches to
      celebrities; 2) attacks and assassinations of public figures, usually the
      President of the United States; 3) threats and approaches to legislative members
      of state and federal governments; and 4) threats, approaches, and attacks against
      federal judicial officials. Similarities and differences across the various
      studies are discussed. Consistent findings across the studies indicate that
      direct threats toward the target are unusual and are often correlated negatively
      with an approach or attack; a significant proportion of subjects are mentally ill
      and have criminal histories; many subjects evidenced a downward spiral in their
      lives in the months or year before their approach or attack; and if an attack
      occurred, it was predatory (instrumental, premeditated) rather than affective
      (emotional, reactive), and the weapon of choice was a firearm, usually a handgun.
      Operational guidance and further research recommendations are made.

PMID- 15461117
TI  - Analysis of nitrite in adulterated urine samples by capillary electrophoresis.
AB  - A simple method for analyzing nitrite in urine has been developed to confirm and
      quantify the amount of nitrite in potentially adulterated urine samples. The
      method involved separation of nitrite by capillary electrophoresis and direct UV
      detection at 214 nm. Separation was performed using a bare fused silica capillary
      and a 25 mM phosphate run buffer at a pH of 7.5. Sample preparation consisted of
      diluting the urine samples 1:20 with run buffer and internal standard, and
      centrifuging for 5 min at 2500 rpm. The sample was hydrodynamically injected,
      then separated using -25 kV with the column maintained at 35 degrees C. The
      method had upper and lower limits of linearity of 1500 and 80 microg/mL nitrite,
      respectively, and a limit of detection of 20 microg/mL. The method was evaluated
      using the National Committee for Clinical Laboratory Standards (NCCLS) protocol
      (Document EP10-A2), and validated using controls, standards, and authentic urine
      samples. Ten anions, ClO-, CrO4(-2), NO3-, HCO3-, I-, CH3COO-, F-, SO4-, S2O8(
      2), and Cl-, were tested for potential interference with the assay. Interferences
      with quantitation were noted for only CrO4(-2) and S2O8(-2). High concentrations
      of Cl- interfered with the chromatography. The method had acceptable accuracy,
      precision, and specificity.

PMID- 15461118
TI  - Tramadol (Ultram) concentrations in death investigation and impaired driving
      cases and their significance.
AB  - We reviewed a series of 66 deaths in Washington State between 1995-2000 in which
      tramadol (Ultram and Ultracet, Ortho-McNeil) was detected in the decedent's
      blood, in order to assess the role tramadol was determined to have played.
      Additionally, we reviewed a series of 83 impaired driving cases in which tramadol
      was detected in order to establish a non-lethal blood tramadol concentration
      reference range. In both populations, tramadol was consistently found together
      with other analgesic, muscle relaxant, and CNS depressant drugs. Death was rarely
      attributable to tramadol alone. However, tramadol may be a significant
      contributor to lethal intoxication when taken in excess with other drugs, via the
      potential interaction with serotonergic antidepressant medications, as well as
      the potential for increased CNS depression. Although the incidence of tramadol
      detection has increased consistently over the last eight years, there is no
      evidence of a corresponding increase in the number of cases in which death was
      attributed solely to tramadol. Blood drug concentrations in many deaths exceeded
      the therapeutic serum range of 0.28-0.61 mg/L; however, the concentrations
      overlapped almost completely with the range identified in living subjects
      arrested for impaired driving. These findings suggest caution in the
      interpretation of blood tramadol concentrations outside of the recognized
      therapeutic range. It also suggests that the drug, even when used in moderate
      excess, is not a principle cause of death in suicidal or accidental deaths.

PMID- 15461119
TI  - Use of MDA (the "love drug") and methamphetamine in Toronto by unsuspecting users
      of ecstasy (MDMA).
AB  - It has recently been reported that purity of illicit tablets of ecstasy (MDMA) is
      now high. Our objective was to confirm whether hair of drug users, who request
      only ecstasy from their supplier, contains MDMA in the absence of other drugs. GC
      MS analysis of scalp hair segments disclosed the presence of MDMA in 19 of 21
      subjects and amphetamine/methamphetamine in eight subjects. Surprisingly, seven
      subjects had hair levels of the MDMA metabolite, MDA, equal to or greater than
      those of MDMA, suggesting use of MDA in addition to that of MDMA. These
      amphetamine derivatives might be included by clandestine laboratories to enhance
      effects of the drug cocktail or because of a perception that MDA synthesis might
      be simpler than that of MDMA. Drug users and investigators examining possible
      brain neurotoxic effects of MDMA need to consider that "ecstasy" tablets can
      contain MDA and methamphetamine despite no demand for the drugs.

PMID- 15461120
TI  - Effect of eight solvents on ethanol analysis by Drager 7110 Evidential breath
      analyzer.
AB  - The Drager 7110 MK III FIN Evidential breath analyzer is classified as a
      quantitative analyzer capable to provide sufficient evidence for establishing
      legal intoxication. The purpose of this study was to evaluate ethanol specificity
      of this instrument in the presence of other solvents. Effects of eight possible
      interfering compounds on ethanol analysis were determined in a procedure
      simulating a human breathing. Most of the compounds studied had either a
      negligible effect on ethanol analysis (acetone, methyl ethyl ketone, and methyl
      isobutyl ketone) or were detected in very low concentrations before influencing
      ethanol readings (methanol, ethyl acetate, and diethyl ether). However, 1
      propanol and 2-propanol increased the ethanol readings significantly. Thus,
      Drager ethanol readings should be interpreted carefully in the presence of
      propanol.

PMID- 15461121
TI  - Accidental insulin overdose.
AB  - Exogenous insulin has been used for many years to treat diabetes mellitus. Due to
      the complex nature of insulin therapy, there have been numerous accidental
      overdoses by these patients. Unfortunately, in other instances, insulin has been
      used as an agent for suicide and homicide in diabetics as well as nondiabetics.
      Presented here is a fatal case of accidental insulin overdose in a nondiabetic.
      Following the case presentation, we review insulin pharmacology and the methods
      of diagnosing insulin overdose postmortem. In any case of insulin overdose, a
      comprehensive scene investigation to document the amount and type of insulin
      used, along with information revealing the source of the insulin is critical. In
      addition, a complete autopsy, including appropriate laboratory studies, is needed
      to make a diagnosis in these cases. Proper attention should be given to
      collection and storage of blood samples, as these specimens often yield the
      strongest evidence of insulin overdose.

PMID- 15461122
TI  - Allele frequency data for Profiler Plus Loci in Australia.

PMID- 15461123
TI  - Genotype distribution of DYS385 and D10S676 in Chinese Han population of Yunnan
      Province.

PMID- 15461124
TI  - Genetic data of eight Y-chromosome STRs in males from Santa Catarina, Brazil.

PMID- 15461125
TI  - Analysis of penta D (15q) and penta E (21q) STR polymorphism in a southern
      Italian population sample.

PMID- 15461126
TI  - Allelic frequencies of three X-Y homologous STR loci in Chinese population.

PMID- 15461127
TI  - Polymorphism of 9 STRs in ethnic Chinese population of Malaysia.

PMID- 15461128
TI  - Commentary on: Carter D O, Tibbett M.; Taphonomic mycota: fungi with forensic
      potential. J Forensic Sci 2003;48(1): 168-71.

PMID- 15461129
TI  - Commentary on: Huxley AK, Finnegan M.; Human remains sold to the highest bidder!
      A snapshot of the buying and selling of human skeletal remains on eBay, and
      internet auction site. J Forensic Sci Jan. 2004;(49)1:17-20.

PMID- 15461130
TI  - Buzz factor of one.

PMID- 15461131
TI  - Stress on the farm and its association with injury.
AB  - The objectives of this study were to examine associations between perceived
      psychosocial stress and farm injury among men and women in Ontario, Canada. Cross
      sectional data from the Ontario Farm Family Health Study were used to investigate
      perceived levels of stress, farm injuries and their interrelationships. Age
      standardized rates of injury were 13.3/100/year and 3.8/100/year for men and
      women, respectively. The most common types of injury were strains/sprains/torn
      ligaments and cuts/lacerations. Approximately 18% of men and 11% of women
      reported that their lives were "very stressful." Common sources of stress were
      money worries and feeling overworked. The risk for farm injury increased with
      level of stress. For men, the adjusted odds ratios for injury were: 1.00
      (referent), 1.02 (95% CI: 0.72, 1.42), and 1.61 (95% CI: 1.08, 2.41)for lowest to
      highest stress levels, respectively. For women, adjusted odds ratios were: 1.00
      (referent), 1.43 (95% CI: 0.83, 2.47), and 2.73 (95% CI: 1.38, 5.39). These risks
      were especially pronounced among women who were not employed off the farm. This
      study represents a novel quantitative analysis examining associations between
      perceived psychological stress and farm injury. Future research should
      investigate these associations in other farm populations, confirm their temporal
      directions, and further explore the effect of gender on the strength of these
      associations.

PMID- 15461132
TI  - Effect of age on hospitalized machine-related farm injuries among the
      Saskatchewan farm population.
AB  - Machinery-related injuries are the leading cause of fatal and hospitalized
      injuries on Canadian farms. In Saskatchewan, the proportion of all farm injuries
      related to farm machinery exceeds that reported for all of Canada. This project
      examined the relationship between age and various factors associated with farm
      machine-related injuries in Saskatchewan. A retrospective review of hospital
      discharge data from the administrative data set of Saskatchewan Health was
      conducted using external cause of injury codes to identify cases of farm
      machinery injury that occurred in Saskatchewan during the period April 1, 1990,
      to March 31, 2000. Log linear estimates of association of various factors in four
      age groups were derived. There were 1,493 hospitalizations attributed to farm
      machinery-related injuries. Among the injured cohort, age was a predictor of the
      rate of injury. Significant association for nature of injury, mechanism of
      injury, and type of machine varied by age group. These data provide insights for
      a case-control study of farm machinery-related injuries with the objective of
      determining personal, environmental, and machine-related factors that are
      responsible for this serious public health issue.

PMID- 15461133
TI  - Ergonomic analysis of New York apple harvest work using a Posture-Activities
      Tools-Handling (PATH) work sampling approach.
AB  - Although back, neck, and shoulder strains are common among migrant and seasonal
      orchard workers, little data currently exist regarding the ergonomic factors
      contributing to this problem. We adapted Posture-Activities-Tools-Handling (PATH)
      instruments and methods for ergonomic job analysis of apple harvest work in three
      New York orchards, and used the resulting protocol to quantify hazardous
      activities, loads, and postures. Using a prototype developed previously, we
      trained twelve contract orchard observers with classroom training and supervised
      orchard practice. The PATH data were then collected on 14 orchard workers over
      four days (2,900 observations). Mean coefficients of variation ranged from a low
      of 0.212 (standing leg neutral) to a high of 0.603 (trunk moderate flexion). Most
      frequently observed activities were: picking (62.9%), placing and moving apples
      in the bag (8. 7%), and walking (8.1%). Weight bearing (>10 lb, >4.54 kg) was
      observed 78.5% of the time throughout a range of activities. Apple harvest work
      is comparable with other ergonomically high-risk occupations. Future research
      should focus on low-cost interventions that reduce load and awkward postures.

PMID- 15461134
TI  - Assessing pesticide safety knowledge among Hispanic migrant farmworkers in
      Oregon.
AB  - The purpose of this article is to report on the development and initial use of a
      pesticide knowledge test (PKT) specifically designed to evaluate agricultural
      workers' knowledge of the content mandated by the federal Worker Protection
      Standard (WPS). The PKT is a 20-item, true-false test, used in a sample of 414
      adult and adolescent migrant farmworkers in Oregon. The overall mean score, i.e.,
      number correct, was 15.67(78.4%), with both adults and adolescents demonstrating
      the most difficulty with questions related to the overall health effects of
      pesticides. The internal consistency was 0.73, when estimated using a method to
      correct for small sample sizes. Only six items had less than 70% correct answers.
      Content validity was achieved by basing the items directly on the Worker
      Protection Standard; face validity was obtained by having the final version of
      the test reviewed by a bilingual (English-Spanish) educator familiar with the
      requirements of the WPS. Overall, adult participants scored better than
      adolescents, and those with previous pesticide training scored better than those
      without. There were no differences in scores based on gender or whether the test
      was taken in English or Spanish; however, participants who spoke indigenous
      languages scored significantly lower than those who did not. These results
      indicate that the PKT is a valid, reliable measure of worker knowledge of the
      content of the WPS, although it does not measure the extent to which that
      knowledge is actually used in the work setting.

PMID- 15461135
TI  - Comparison of operator exposure for five different greenhouse spraying
      applications.
AB  - The European Crop Protection Association (ECPA) and the Agricultural Research
      Center (CLO-DVL) joined forces in a project to stimulate the safe use of
      pesticides in southern European countries. CLO-DVL optimized a method using
      mineral chelates as tracers on collectors. This quantitative method to evaluate
      spray deposits was used to compare operator exposure from several greenhouse
      spraying techniques. Operator exposure measurements were of a comparative nature.
      Five application methods were investigated: a standard spray gun with an operator
      walking forwards, a spray lance with an operator walking forwards and backwards,
      a trolley, and a vehicle, both with vertical spray booms. The exposure was
      measured with patches at 15 places on operators' coveralls and gloves, using
      mineral chelates as tracer elements. The difference in exposure of the patches
      between the different techniques was very high. Walking backwards reduced
      exposure by a factor of 7. The exposures with the trolley and the vehicle, two
      innovative spraying techniques, were respectively 25 and 100 times lower compared
      to exposure with the standard spray gun. Operator exposure while walking forward
      with the spray lance was about two times higher than with the spray gun. Besides
      very large differences in exposure among the five techniques, there were also
      large differences in exposure among various parts of the body. All of this is
      important in consideration of operator safety and for the parts of the body that
      need to be protected most.

PMID- 15461136
TI  - Safe tractor access platforms: from guidance material to implementation.
AB  - This article reports on the implementation of published guidelines for
      retrofitting tractors with safe access platforms, which were developed to reduce
      the risk of serious injuries and deaths associated with mounting and dismounting.
      Farmer interviews and engineering-based inspections of ten retrofitted tractors
      were conducted to gather information regarding benefits and disadvantages of the
      retrofitting and to assess the construction of the platforms. A scoring system
      was developed for platform retrofitting, and weighted scores between zero and ten
      were calculated for tractor access before and after retrofitting. Access was
      improved on all tractors, although to varying degrees. The average post-retrofit
      weighted score was 6.3 (range 2.6 to 9.7), compared with the pre-retrofit average
      of 0.9 (range 0.3 to 1.6). Five tractors received a post-retrofit score of 8.0 or
      higher. None of the lower-scoring tractors fully met the specifications for
      placement of the bottom step or rear wheel guard, two key characteristics for
      runover prevention. Other characteristics associated with a lower post-retrofit
      score included a low bottom step, high step rises, absence of colored nosing, and
      the front handrail space not being filled in. Platform retrofitting had little
      effect on tractor operations and substantially improved ease of access. This is
      the first published evaluation of a design-based solution for tractor runover
      injuries. This study shows that general guidelines for retrofitting of safe
      access platforms can be successfully applied. Mechanisms to increase adherence to
      the key criteria of bottom step positioning and rear wheel guarding should be
      included in future promotion.

PMID- 15461137
TI  - Rapid isolation of high-quality total RNA from taxus and ginkgo.
AB  - An easy and efficient protocol was developed for isolating good-quality total RNA
      from various tissues including fruits, leaves, stems, and roots of ancient
      gymnosperm species, taxus and ginkgo. The protocol was developed based on the
      CTAB method with modifications, including higher-strength CTAB to help the lysis
      of plant cells, more PVP, and beta-mercaptoethanol to prevent oxidation of
      phenolic complexes, and higher-centrifugation force to get rid of most cell
      debris and to ensure RNA quality. In RNA isolation, chloroform/isoamyl alcohol
      was used to remove proteins, genomic DNA, and secondary metabolites and lithium
      chloride was subsequently adopted to concentrate total RNA away from most of the
      cytoplasmic components. Good-quality total RNA from various tissues of native
      taxus and ginkgo could be easily isolated within 24 hr by this protocol which
      avoided the limitation of plant materials and the usage of dangerous chemicals,
      such as phenol, and could provide total RNA for all kinds of further molecular
      studies.

PMID- 15461138
TI  - Fusion expression of human beta-defensin-2 from multiple joined genes in
      Escherichia coli.
AB  - Human beta-defensin-2 (hBD-2) is a cysteine-rich cationic low molecular weight
      antimicrobial peptide, which exhibits a broad range of antimicrobial activity
      without observed acquired resistance. In this work, multiple copies of the hBD-2
      gene were linked in tandem and the expression of the multiple joined genes in two
      fusion expression system, pET28a(+) and pGEX-4T-2, was examined. Using plasmid
      pET28a(+) with one, two, and four copies of the hBD-2 gene, the expressed level
      was relatively low, whereas much higher with plasmid pGEX-4T-2, and the fusion
      products, most of which in insoluble form, account for approximately 26% of the
      total insoluble cellular proteins.

PMID- 15461139
TI  - Antigenic activity of three chimeric synthetic peptides of the transmembrane
      (gp41) and the envelope (gp120) glycoproteins of HIV-1 virus.
AB  - The antigenicity of three chimeric synthetic peptides (Qm, Qm-16, and Qm-17)
      incorporating an immunodominant epitope of the gp41 transmembrane protein (587
      617) and the different epitopes of the gp120 envelope protein (495-516), (301
      335), (502-516) of human immunodeficiency virus (HIV-1), separated by two glycine
      residues, was evaluated by UltramicroEnzyme-linked immunosorbent assay (UMELISA)
      by using panels of anti-HIV-1 positive sera (n = 47). The specificity was
      evaluated with samples from healthy blood donors (n = 20) and anti-HIV-2 positive
      samples (n = 10). The results indicate that the chimeric peptide, Qm, was the
      most reactive one because it detected antibodies to virus efficiently. This may
      be related to peptide adsorption onto the solid surface, the C-terminal region of
      HIV-1 gp120 (495-516) combined with gp41 (587-617) in the chimera, and the
      epitope accessibility to the antibodies. This study showed the usefulness of the
      chimeric peptides as antigen to detect antibodies to HIV-1 virus.

PMID- 15461140
TI  - Purification and identification of recombinant hirudin and its degradation
      products expressed in Pichia pastoris.
AB  - The purification and identification of recombinant hirudin (r-hirudin) (rHV2
      Lys47) and its several C-terminal proteolytic degradation derivatives, produced
      by Pichia pastoris, were described. The high-purity rHV2-Lys47 of above 99% and
      its three degradation products were obtained by a straightforward two-step
      chromatography procedure, a combination of cation exchange and reverse phase
      chromatography, with a recovery yield of 74% for hirudin. The purified rHV2 had
      the predicted N-terminal amino acid sequence and the derivatives were the
      degradation products of hirudin, short of one to three amino acid residues at C
      terminal.

PMID- 15461141
TI  - Purification and characterization of an anionic isoperoxidase from scented
      geranium callus.
AB  - Secretory anionic isoperoxidase (EC 1.11.1.7), named PA1, was 68-fold purified
      from scented-geranium (Pelargonium graveolense) callus by using ion exchange
      chromatography and gel filtration. Isoperoxidase PA1 was a glycoprotein with an
      isoelectric point (pI) of 4.0. The molecular weight of PA1 was approximately 42.5
      and 44 kDa, estimated by SDS-PAGE and Sephadex G-150 gel filtration,
      respectively. The optimum pH of the enzyme was 5.0 for guaiacol and H2O2, and the
      Km values for guaiacol and H2O2 were 1.96 and 8.5mM, respectively. Substrate
      studies in terms of optimum pHs and Km values with various synthetic and
      naturally occurring phenolic compounds were performed. In comparison with
      cationic isoperoxidase, PC3, which has been already characterized, anionic
      isoperoxidase PA1 had much lower Km values for synthetic phenolic compounds and
      much higher Km values for naturally occurring phenolic compounds than PC3.
      Moreover, anionic isoperoxidase PA1 could utilize ferulic acid as a substrate
      very well, while cationic isoperoxidase PC3 could not utilize ferulic acid as a
      substrate.

PMID- 15461142
TI  - Expression of human metallothionein III and its metalloabsorption capability in
      Escherichia coli.
AB  - Human metallothionein III (MT III) gene was synthesized with Escherichia coli
      preference codon usage and expressed in E. coli in glutathione-S-transferase
      (GST) fusion form. The recombinant MT III was released by proteinase Factor Xa
      digestion and purified with the yield of 2 mg/L culture, and its specific Cd2+
      binding capability was confirmed. E. coli strain BL21(DE3), expressing MT III,
      showed metal tolerance between 0.1 and 0.5 mM Cd2+ and bacterial growth was
      inhibited at 1 mM Cd2+. MT III expressing E. coli strain showed binding
      discrimination between different metal ions in combination use, with the
      preference order of Cd2+ > Cu2+ > Zn2+. It absorbed different metal ions with
      relatively constant ratio and showed a cumulative absorption capability for mixed
      heavy metals.

PMID- 15461143
TI  - Purification and some properties of isocitrate dehydrogenase from Paracoccus
      denitrificans.
AB  - NADP-dependent isocitrate dehydrogenase (ICDH) from the bacterium Paracoccus
      denitrificans was purified to homogeneity. The purification procedure involved
      ammonium sulphate fractionation, ion exchange chromatography, and gel permeation
      chromatography. The specific activity of purified ICDH was 801 nkat/mg, the yield
      of the enzyme 58%. The purity of the enzyme was checked by polyacrylamide gel
      electrophoresis in the presence of sodium dodecyl sulphate. ICDH is a dimer
      composed of two probably identical subunits of relative molecular weight 90,000.
      The pH optimum of the enzyme reaction in the direction of substrate oxidation was
      found to be 5.6; the presence of Mn2+ is essential for enzyme activity. The
      absorption and fluorescence spectra of the homogeneous enzyme were measured as
      well.

PMID- 15461144
TI  - Top 10 environmental success stories.

PMID- 15461145
TI  - 2003 blackout cleaned the air.

PMID- 15461146
TI  - Bigger EU could affect environmental policies.

PMID- 15461147
TI  - U.S. forest fire policies get flamed.

PMID- 15461148
TI  - Leaded gasoline phaseout becoming a reality.

PMID- 15461149
TI  - Low-tech solution for pasteurizing water.

PMID- 15461150
TI  - Modeling the long-term perfomance of waste containment systems.

PMID- 15461151
TI  - Chemical characterization of ambient particulate matter near the World Trade
      Center: elemental carbon, organic carbon, and mass reconstruction.
AB  - Concentrations of elemental carbon (EC), organic carbon matter (OM), particulate
      matter less than 2.5 microm (PM2.5), reconstructed soil, trace element oxides,
      and sulfate are reported from four locations near the World Trade Center (WTC)
      complex for airborne particulate matter (PM) samples collected from September
      2001 through January 2002. Across the four sampling sites, daily mean
      concentrations ranged from 1.5 to 6.8 microg/m3 for EC, from 10.2 to 31.4
      microg/m3 for OM, and from 22.6 to 66.2 microg/m3 for PM2.5. Highest
      concentrations of PM species were generally measured north and west of the WTC
      complex. Total carbon matter and sulfate constituted the largest fraction of
      reconstructed PM2.5 concentrations. Concentrations of PM species across all sites
      decreased from the period when fires were present at the WTC complex (before
      December 19, 2001) to the period after the fires. Averaged over all sites,
      concentrations decreased by 25.6 microg/m3 for PM2.5, 2.7 microg/m3 for EC, and
      9.2 microg/m3 for OM from the fire period to after fire period.

PMID- 15461152
TI  - Using passive air samplers to assess urban-rural trends for persistent organic
      pollutants. 1. Polychlorinated biphenyls and organochlorine pesticides.
AB  - Passive air samplers were used to investigate urban-rural differences of
      polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) over an
      integrated time period. Samplers consisting of polyurethane foam (PUF) disks and
      semi-permeable membrane devices (SPMDs) were housed in protective chambers and
      deployed at six sites for a 4 month duration in the summer of 2000. The sampling
      transect originated in downtown Toronto and extended approximately 75 km
      northward into a rural region. Results for the two types of samplers agreed well
      with one another. Higher blank levels were encountered for the SPMDs, especially
      for the OCPs, whereas blanks were very low for the PUF disks. Passive sampler
      derived air concentrations were consistent with previous measurements of PCBs and
      OCPs in the region. The largest urban-rural gradient was observed for PCBs
      (approximately 5-10 times). Chlordanes also showed an urban-rural gradient,
      possibly reflecting past usage of chlordane on residential lawns and emissions
      from treated house foundations. Other OCPs exhibited a rural-urban gradient
      (dieldrin, endosulfan 1, and DDT isomers), which was attributed either to off
      gassing from previously treated agricultural soils (dieldrin and DDTs) or to
      continued usage in agriculture (endosulfan 1). The results of this study
      demonstrated the feasibility of using such devices to determine air
      concentrations of persistent organic pollutants (POPs) and to assess their
      spatial distribution for time-integrated samples. Data such as this is essential
      for: model validation and for process research and addressing international
      monitoring strategies on POPs.

PMID- 15461153
TI  - Tracking polybrominated diphenyl ether releases in a wastewater treatment plant
      effluent, Palo Alto, California.
AB  - Polybrominated diphenyl ethers (PBDEs) are commonly used flame-retardants that
      are now ubiquitous environmental contaminants. Wastewater treatment plants are
      one source of PBDEs to the environment through their discharge of treated
      effluent and land application of sewage sludge. Effluent and sludge were
      collected and analyzed for PBDEs at a wastewater treatment plant in California.
      The total concentration of PBDEs ranged from 61 to 1440 microg/kg dry wt in the
      sludge and from 4 to 29,000 pg/L in discharged effluent. The congeners with the
      highest abundance in sludge were BDE-47, BDE-99, and BDE-209, while in treated
      effluent BDE-47 and BDE-99 were the most abundant. BDE-47 and BDE-99 are major
      congeners of the penta-formulation, while BDE-209 composes the deca-formulation.
      The sum of the major congeners in the penta-formulation (BDE-47, 99, 100, 153,
      and 154) comprises 88% of the total PBDEs in the effluent, while BDE-209 is only
      6%. Based on the loading analysis, the total PBDE concentrations loaded to the
      San Francisco Estuary through effluent discharge from this wastewater treatment
      plant is 2 lb/year (0.9 kg/year).

PMID- 15461154
TI  - Perfluorooctanesulfonate and related fluorochemicals in human blood from several
      countries.
AB  - Perfluorooctanesulfonyl fluoride based compounds have been used in a wide variety
      of consumer products, such as carpets, upholstery, and textiles. These compounds
      degrade to perfluorooctanesulfonate (PFOS), a persistent metabolite that
      accumulates in tissues of humans and wildlife. Previous studies have reported the
      occurrence of PFOS, perfluorohexanesulfonate (PFHxS), perfluorooctanoate (PFOA),
      and perfluorooctanesulfonamide (PFOSA) in human sera collected from the United
      States. In this study, concentrations of PFOS, PFHxS, PFOA, and PFOSA were
      measured in 473 human blood/serum/plasma samples collected from the United
      States, Colombia, Brazil, Belgium, Italy, Poland, India, Malaysia, and Korea.
      Among the four perfluorochemicals measured, PFOS was the predominant compound
      found in blood. Concentrations of PFOS were the highest in the samples collected
      from the United States and Poland (>30 ng/mL); moderate in Korea, Belgium,
      Malaysia, Brazil, Italy, and Colombia (3 to 29 ng/mL); and lowest in India (<3
      ng/mL). PFOA was the next most abundant perfluorochemical in blood samples,
      although the frequency of occurrence of this compound was relatively low. No age-
      or gender-related differences in the concentrations of PFOS and PFOA were found
      in serum samples. The degree of association between the concentrations of four
      perfluorochemicals varied, depending on the origin of the samples. These results
      suggested the existence of sources with varying levels and compositions of
      perfluorochemicals, and differences in exposure patterns to these chemicals, in
      various countries. In addition to the four target fluorochemicals measured,
      qualitative analysis of selected blood samples showed the presence of other
      perfluorochemicals such as perfluorodecanesulfonate (PFDS), perfluoroheptanoic
      acid (PFHpA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA),
      perfluorododecanoic acid (PFDoA), and perfluoroundecanoic acid (PFUnDA) in serum
      samples, at concentrations approximately 5- to 10-fold lower than the
      concentration of PFOS. Further studies should focus on identifying sources and
      pathways of human exposure to perfluorochemicals.

PMID- 15461155
TI  - An FTIR-DRIFT study on river sediment particle structure: implications for
      biofilm dynamics and pollutant binding.
AB  - Diffuse reflectance infrared Fourier transform (DRIFT) spectrometry was applied
      to a set of sediment samples collected by traps over one and a half years in a
      mid-mountainous river. Dynamic changes in hydrological and life-cycle conditions
      generated sediment particles of different C(org) content and organic composition.
      Periods in the midst of or shortly after flood events left particles poor in
      C(org) content with spectral features that were enriched in carboxylic and
      aromatic signals. These are characteristic of terrestrial oxidized vascular plant
      debris. Low-flow conditions saw the consequent build-up of amide, aliphatic, and
      polysaccharide moieties as expected for autochthonous biofilm derived material. A
      peak ratio of two bands representing the alternation of these two types of
      organic matter showed that flood particle C(org) had a higher affinity for metals
      than the high C(org) of mature biofilms, probably owing to higher COO- contents
      in the first. The relative dietary bioavailability of the metals from sediment
      C(org), which is related to the nutritional value of the substrate, is therefore
      probably lower in the aftermath of a flood than in prolonged low-flow situations.
      This needs to be accounted for in future metal speciation and bioavailability
      modeling approaches.

PMID- 15461156
TI  - Uptake of sediment-bound bioavailable polychlorobiphenyls by benthivorous carp
      (Cyprinus carpio).
AB  - It is unclear whether accumulation of sediment-bound chemicals in benthivorous
      fish depends on the degree of sequestration in the sediment like it does for
      invertebrates. Here, we report on the potential of slow and fast desorbing
      sediment-bound polychlorobiphenyl (PCB) fractions for accumulation in carp
      (Cyprinus carpio) in lake enclosures treated with different nutrient doses.
      Routes of PCB uptake were quantitatively evaluated for 15 PCBs (log Kow range 5.6
      7.8) using model analysis. Fast-desorbing PCB fractions in the sediment were
      defined as the ratio of 6-h Tenax-extractable to (total) Soxhlet-extractable
      concentrations. These fractions varied between 4 and 22% and did not show a clear
      trend with log Kow. However, bioaccumulation of PCBs in carp correlated much
      better with Tenax-extractable concentrations than with total-extractable
      concentrations. Nutrient additions in the enclosures had a positive effect on PCB
      accumulation. Model results showthat PCB uptake in carp can be explained from (1)
      uptake through invertebrate food, (2) uptake from fast-desorbing fractions in
      ingested sediments, and (3) uptake from water, where PCBs are in partitioning
      equilibrium with fast-desorbing fractions. The main implication of this research
      is that fast-desorbing PCB fractions in sediments have great predictive potential
      for bioaccumulation in benthivorous fish.

PMID- 15461157
TI  - Sorption of the herbicide dichlobenil and the metabolite 2,6-dichlorobenzamide on
      soils and aquifer sediments.
AB  - The worldwide used herbicide dichlobenil (2,6-dichlorobenzonitrile) has resulted
      in widespread presence of its metabolite 2,6-dichlorobenzamide (BAM) in pore- and
      groundwater. To evaluate the transport of these compounds we studied the sorption
      of dichlobenil and BAM in 22 sediment samples of clayey till, sand, and limestone
      including sediments exhibiting varying oxidation states. Dichlobenil sorbed to
      all investigated sediments, with a high sorption in topsoils (Kd = 7.4-17.4 L kg(
      1)) and clayey till sediments (Kd = 2.7-126 L kg(-1)). The sorption of the polar
      metabolite BAM was much lower than the sorption of dichlobenil but followed the
      same tendency with the highest sorption in the topsoils (Kd = 0.24-0.66 L kg(-1))
      and in the clayey till sediments (Kd = 0.10-0.93 L kg(-1)). The sorption of both
      compounds was significantly higher (2-47 times) in the unoxidized (reduced)
      clayey till than in the weathered (oxidized) clayey till. Such a difference in
      sorption capacity could neither be explained by a higher organic carbon content,
      sorption to clay minerals, differences in clay mineralogy, nor by blocking of
      reactive surface sites on clay minerals by iron oxides. However, by removing an
      average of 81% of the organic carbon from the reduced clayey till with H2O2, the
      sorption decreased on average 50%. Therefore, most of the sorption capacity in
      the reduced clayey till was related to organic carbon, which indicates that
      sorption processes are affected by changes in organic compound composition due to
      weathering.

PMID- 15461158
TI  - Food web pathway determines how selenium affects aquatic ecosystems: a San
      Francisco Bay case study.
AB  - Chemical contaminants disrupt ecosystems, but specific effects may be under
      appreciated when poorly known processes such as uptake mechanisms, uptake via
      diet, food preferences, and food web dynamics are influential. Here we show that
      a combination of food web structure and the physiology of trace element
      accumulation explain why some species in San Francisco Bay are threatened by a
      relatively low level of selenium contamination and some are not. Bivalves and
      crustacean zooplankton form the base of two dominant food webs in estuaries. The
      dominant bivalve Potamocorbula amurensis has a 10-fold slower rate constant of
      loss for selenium than do common crustaceans such as copepods and the mysid
      Neomysis mercedis (rate constant of loss, ke = 0.025, 0.155, and 0.25 d(-1),
      respectively). The result is much higher selenium concentrations in the bivalve
      than in the crustaceans. Stable isotope analyses show that this difference is
      propagated up the respective food webs in San Francisco Bay. Several predators of
      bivalves have tissue concentrations of selenium that exceed thresholds thought to
      be associated with teratogenesis or reproductive failure (liver Se >15 microg g(
      1) dry weight). Deformities typical of selenium-induced teratogenesis were
      observed in one of these species. Concentrations of selenium in tissues of
      predators of zooplankton are less than the thresholds. Basic physiological and
      ecological processes can drive wide differences in exposure and effects among
      species, but such processes are rarely considered in traditional evaluations of
      contaminant impacts.

PMID- 15461159
TI  - Arsenic speciation of solvent-extracted leachate from new and weathered CCA
      treated wood.
AB  - For the past 60 yr, chromate-copper-arsenate (CCA) has been used to pressure
      treat millions of cubic meters of wood in the United States for the construction
      of many outdoor structures. Leaching of arsenic from these structures is a
      possible health concern as there exists the potential for soil and groundwater
      contamination. While previous studies have focused on total arsenic
      concentrations leaching from CCA-treated wood, information pertaining to the
      speciation of arsenic leached is limited. Since arsenic toxicity is dependent
      upon speciation, the objective of this study was to identify and quantify arsenic
      species leaching from new and weathered CCA-treated wood and CCA-treated wood
      ash. Solvent-extraction experiments were carried out by subjecting the treated
      wood and the ash to solvents of varying pH values, solvents defined in the EPA's
      Synthetic Precipitation Leaching Procedure (SPLP) and Toxicity Characteristic
      Leaching Procedure (TCLP), rainwater, deionized water, and seawater. The
      generated leachates were analyzed for inorganic As(III) and As(V) and the
      organoarsenic species, monomethylarsonic acid (MMAA) and dimethylarsinic acid
      (DMAA), using high-performance liquid chromatography followed by hydride
      generation and atomic fluorescence spectrometry (HPLC-HG-AFS). Only the inorganic
      species were detected in any of the wood leachates; no organoarsenic species were
      found. Inorganic As(V) was the major detectable species leaching from both new
      and weathered wood. The weathered wood leached relatively more overall arsenic
      and was attributed to increased inorganic As(III) leaching. The greater presence
      of As(III) in the weathered wood samples as compared to the new wood samples may
      be due to natural chemical and biological transformations during the weathering
      process. CCA-treated wood ash leached more arsenic than unburned wood using the
      SPLP and TCLP, and ash samples leached more inorganic As(III) than the unburned
      counterparts. Increased leaching was due to higher concentrations of arsenic
      within the ash and to the conversion of some As(V) to As(III) during combustion.

PMID- 15461160
TI  - Antimony(III) binding to humic substances: influence of pH and type of humic
      acid.
AB  - Conditional distribution coefficients (Dom) for Sb(III) binding to three
      commercial humic acids (terrestrial, coal, and aquatic) were measured at
      environmentally relevant Sb(III)/DOC ratios and as a function of pH using an
      equilibrium dialysis method. Maximum binding of Sb(III) was observed around pH 6
      for two of the humic acids. The third humic acid showed constant Dom values up to
      pH 6 and decreasing Dom values for pH > 6. Sb(III)/DOC ratio was found to be
      important for Dom (20 times higher Dom for 60 times lower Sb(III)/DOC ratio).
      Moreover, Dom depends on the individual humic acid, suggesting that different
      functional groups are involved and/or different degrees of stabilization by
      chelation or H-bridges. Chemical modeling of Sb(III)-humics binding at different
      pH values is consistent with two binding sites involving (i) a phenolic entity
      forming a neutral complex and (ii) a carboxylic entity forming a negatively
      charged complex. Under environmentally relevant conditions, over 30% of total
      Sb(III) may be bound to natural organic matter.

PMID- 15461161
TI  - Protection of mesopore-adsorbed organic matter from enzymatic degradation.
AB  - Synthetic mesoporous alumina and silica minerals with uniform pore geometries,
      and their nonporous analogues, were used to test the role of mineral mesopores (2
      50 nm diameter) in protecting organic matter from enzymatic degradation in soils
      and sediments. Dihydroxyphenylalanine (L-DOPA), a model humic compound, was
      irreversibly sorbed to both mineral types. The surface area-normalized adsorption
      capacity was greater for the mesoporous minerals relative to their nonporous
      analogues. The degradation kinetics of free and mineral-sorbed L-DOPA by the
      enzyme laccase was monitored in a closed cell via oxygen electrode. Relative to
      freely dissolved L-DOPA, nonporous alumina-sorbed substrate was degraded, on
      average, 90% more slowly and to a lesser extent (93%), likely due to laccase
      adsorption to alumina. In contrast, relative to free L-DOPA, degradation of
      nonporous silica-sorbed L-DOPA was enhanced by 20% on average. In the case of
      mesoporous alumina and silica-sorbed L-DOPA, the enzyme activity was 3-40 times
      lower than that observed for externally sorbed substrate (i.e., L-DOPA sorbed to
      nonporous minerals). These results provide strong evidence to support the
      viability of the mesopore protection mechanism for sequestration and preservation
      of sedimentary organic matter and organic contaminants. Nanopore
      adsorption/desorption phenomena may aid in explaining the slow degradation of
      organic contaminants in certain soils and sediments and may have implications for
      environmental remediation and biotechnological applications.

PMID- 15461162
TI  - Effects of particulate carbonaceous matter on the bioavailability of
      benzo[a]pyrene and 2,2',5,5'-tetrachlorobiphenyl to the clam, Macoma balthica.
AB  - We investigated the bioavailability via diet of spiked benzo[a]pyrene (BaP) and
      2,2',5,5'-tetrachlorobiphenyl (PCB-52) from different carbonaceous (non
      carbonate, carbon containing) particle types to clams (Macoma balthica) collected
      from San Francisco Bay. Our results reveal significant differences in absorption
      efficiency between compounds and among carbonaceous particle types. Absorption
      efficiency for PCB-52 was always greater than that for BaP bound to a given
      particle type. Among particles, absorption efficiency was highest from wood and
      diatoms and lowest from activated carbon. Large differences in absorption
      efficiency could not be simply explained by comparatively small differences in
      the particles' total organic carbon content. BaP and PCB-52 bound to activated
      carbon exhibited less than 2% absorption efficiency and were up to 60 times less
      available to clams than the same contaminants associated with other types of
      carbonaceous matter. These results suggest that variations in the amount and type
      of sediment particulate carbonaceous matter, whether naturally occurring or added
      as an amendment, will have a strong influence on the bioavailability of
      hydrophobic organic contaminants. This has important implications for
      environmental risk assessment, sediment management, and development of novel
      remediation techniques.

PMID- 15461163
TI  - NO2 emissions from agricultural burning in Sao Paulo, Brazil.
AB  - We report here on the application of a compact ultraviolet spectrometer to
      measurement of NO2 emissions from sugar cane field burns in Sao Paulo, Brazil.
      The time-resolved NO2 emission from a 10 ha plot peaked at about 240 g (NO2) s(
      1), and amounted to a total yield of approximately 50 kg of N, or about 0.5 g (N)
      m(-2). Emission of N as NOx (i.e., NO + NO2) was estimated at 2.5 g (N) m(-2),
      equivalent to 30% of applied fertilizer nitrogen. The corresponding annual
      emission of NOx nitrogen from Sao Paulo State sugar cane burning was >45 Gg N. In
      contrast to mechanized harvesting, which does not require prior burning of the
      crop, manual harvesting with burning acts to recycle nitrogen into surface soils
      and ecosystems.

PMID- 15461164
TI  - Effect of tides on solute flushing from a strait: imaging flow and transport in
      the East River with SF6.
AB  - In June 2003, two injections of approximately 3.9 mol of sulfur hexafluoride
      (SF6) were made 8 days apart in the East River, a 25 km tidal strait, to observe
      solute mixing and dissipation. The first injection occurred at slack before
      flood, and the second at slack before ebb (flood = northward flow). Tidally
      synchronized surveys of the SF6 tracer patch, supplemented by vertical profiles,
      were conducted by boat for 6 and 4 days following the flood and ebb injections,
      respectively. Residence times for the tracer-tagged water mass in the East River
      were estimated to be 3.3 +/- 0.7 days and 1.7 +/- 0.5 days for the flood and ebb
      injections, respectively, after correcting SF6 inventories for losses of SF6 from
      the water column by air-water gas exchange. The data indicate that the majority
      of East River solutes are transported to New York Harbor and that tidal mixing
      dominates subtidal circulation with respectto solute transport. Surveys of the
      adjacent lower Hudson River revealed a northward-moving, intermediate layer of
      East River water. Our results suggest that tidal phasing of contaminant
      discharges in the East River could reduce environmental impacts, by increasing
      flushing rates and directing a greater fraction of material away from Long Island
      Sound.

PMID- 15461165
TI  - Metabolism and mineralization of hexahydro-1,3,5-trinitro-1,3,5-triazine inside
      poplar tissues (Populus deltoides x nigra DN-34).
AB  - Poplar tissue cultures and leaf crude extracts (Populus deltoides x nigra DN-34)
      were exposed to [U-14C]hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and
      incubated under light and in the dark. Poplar tissue cultures were able to
      partially reduce RDX to hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and
      hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine (DNX), regardless of the presence
      or absence of light. However, further transformation of RDX, MNX, and DNX
      required exposure to light and resulted in the formation of formaldehyde (CH2O),
      methanol (CH3OH), and carbon dioxide (CO2). Similarly, transformation of RDX by
      poplar leaf crude extracts required exposure to light. Neither reduction of RDX
      to MNX and DNX nor mineralization into CO2 were recorded in crude extracts, even
      when exposed to light, suggesting that both processes were light-independent and
      required intact plant cells. Control experiments without plant material showed
      that RDX was partially transformed abiotically, by the sole action of light, but
      to a lesser extent than in the presence of plant crude extracts, suggesting the
      intervention of plant subcellular structures through a light-mediated mechanism.
      Poplar tissue cultures were also shown to mineralize 14CH2O and 14CH3OH,
      regardless of the presence or absence of light. These results suggest that
      transformation of [U-14C]RDX by plant tissue cultures may occur through a three
      step process, involving (i) a light-independent reduction of RDX to MNX and DNX
      by intact plant cells; (ii) a plant/light-mediated breakdown of the heterocyclic
      ring of RDX, MNX, or DNX into C1-labeled metabolites (CH2O and CH3OH); and (iii)
      a further light-independent mineralization of C1-labeled metabolites by intact
      plant cells. This is the first time that a significant mineralization of RDX into
      CO2 by light-exposed plant tissue cultures is reported.

PMID- 15461166
TI  - Modeling of TCE diffusion to the atmosphere and distribution in plant stems.
AB  - Fate of chlorinated solvents in phytoremediation has been delineated by many
      discoveries made in recent years. Plant uptake, metabolism, rhizosphere
      degradation, accumulation, and volatilization were shown to occur to differing
      degrees for many organic contaminants including chlorinated solvents. Among these
      mechanistic findings, recent research confirmed that volatile organic compounds
      (VOCs) volatilize from stems and that the resulting diffusive flux to the
      atmosphere is related to exposure concentration and to height up the stem. A
      comprehensive model was developed based upon all identified fate and transport
      mechanisms for VOCs, including translocation in the xylem flow and diffusion. The
      dispersion and diffusion in the radial direction were considered as one process
      (effective diffusion) as the two could not be investigated individually. The
      mechanism-based model mathematically indicates an exponential decrease of
      concentrations with height. While an analytic solution for the comprehensive
      model was not attained, it can serve as a starting point for other modeling
      efforts. The comprehensive model was simplified in this work for practical
      application to experimentally obtained data on trichloroethylene (TCE) fate.
      Model output correlated well with experimental results, and effective
      diffusivities for TCE in plant tissues were obtained through the model
      calibrations. The simplified model approximated TCE concentrations in the
      transpiration stream as well as TCE volatilization to the atmosphere. Xylem
      transport, including advection, dispersion, and diffusion through cell walls with
      subsequent volatilization to the atmosphere, is a major fate for VOCs in
      phytoremediation.

PMID- 15461167
TI  - Reduction of aqueous chromate by Fe(II)/Fe(III) carbonate green rust: kinetic and
      mechanistic studies.
AB  - This work describes the heterogeneous reaction between FeII in carbonate green
      rust and aqueous chromate, in NaHCO3 solutions at 25 degrees C, and at pH values
      of 9.3-9.6. Evidence for reduction of CrVI to CrIII and concomitant solid-state
      oxidation of lattice FeII to FeIII was found from FeII titration and from
      structural analysis of the solids using FTIR, XRD, SEM, and XPS methods. Results
      indicate the formation of ferric oxyhydroxycarbonate and the concomitant
      precipitation of CrIII monolayers at the surface of the iron compound that induce
      passivation effects and progressive rate limitations. The number of CrIII
      monolayers formed at the completion of the reaction depends on [FeII]t=0, the
      molar concentration of FeII(solid) at t=0; on [n(o)]t=0, the molar concentration
      of reaction sites present at the surface of the solid phase at t=0; and on
      [CrVI]t=0, the molar concentration of CrVI at t=0. Kinetic data were modeled
      using a model based on the formation of successive CrIII monolayers, 
      (d[CrVI]/dt) = sigma(1)j k(i)[S] [CrVI]([n(i - 1)] - [n(i)]) with k(i)[S] (in s(
      1) L mol(-1)), the rate coefficient of formation of CrIII monolayer i, and [n(i)]
      and [n(i - 1)], the molar concentration of CrIII precipitated in monolayer i and
      monolayer i - 1, respectively. Good matching curves were obtained with kinetic
      coefficients: k(1)[S] = 5-8 x 10(-4), k(2)[S] = 0.5-3 x 10(-5), and k(3)[S] about
      1.7 x 10(-6) s(-1) m(-2) L. The CrVI removal efficiency progressively decreases
      along with the accumulation of CrIII monolayers at the surface of carbonate green
      rust particles. In the case of thick green rust particles resulting from the
      corrosion of iron in permeable reactive barriers, the quantity of FeII readily
      accessible for efficient CrVI removal should be rather low.

PMID- 15461168
TI  - Electrokinetic transport of PAH-degrading bacteria in model aquifers and soil.
AB  - An investigation of the mobility, viability, and activity of polycyclic aromatic
      hydrocarbon (PAH) degrading bacteria in an electric field is presented. Bench
      scale model aquifers were used to test electrophoresis and electroosmosis as
      potential mechanisms for bacterial dispersion in contaminated sites. Glass beads,
      alluvial sand from Lake Geneva, and historically polluted clayey soil were used
      as packing materials. The green-fluorescent protein labeled PAH-degrading
      bacteria Sphingomonas sp. L138 and Mycobacterium frederiksbergense LB501TG were
      used as test organisms because of the known differing physicochemical surface and
      adhesion properties of the corresponding wild-type strains. No adverse effects of
      the electric current on bacterial viability and PAH-degradation were observed in
      the system chosen. Up to 90% of the weakly negatively charged and moderately
      adhesive cells of strain L138 were transported by electroosmosis, whereas 0-20%
      were transported by electrophoresis. By contrast, poor electrokinetic transport
      of strongly charged and highly adhesive cells of M. frederiksbergense LB501TG
      occurred in the different model aquifers. Treatment of bacteria with the nonionic
      surfactant Brij35 resulted in up to 80% enhanced electrokinetic dispersion of
      both strains. Our findings demonstrate that electroosmosis may be a valuable
      mechanism to transport bacteria in the subsurface with transport efficiencies
      heavily depending on the retention of the bacteria by the solid phase.

PMID- 15461169
TI  - Reactions of the flavonoid hesperetin with chlorine: a spectroscopic study of the
      reaction pathways.
AB  - The flavonoid hesperetin (Hsp) contains aromatic rings substituted with hydroxyl
      and methoxyl groups, which activate it toward electrophilic attack and hence make
      it a potential surrogate for natural organic matter with respect to reactions
      with chlorine. This paper describes the chlorination pathway of Hsp, based on a
      combination of electrospray tandem mass spectrometry (MS/MS) and absorbance
      spectroscopy. When a solution containing Hsp is dosed with NaOCl at pH 7,
      chlorine substitution into Hsp occurs exclusively into the meta-dihydroxy
      substituted ring. The first two Cl atoms to enter the ring do so at the highly
      activated carbons that are each ortho to two oxygenated carbon atoms. These
      substitutions make the molecule more acidic, but do not change its primary
      structure or aromaticity. The third Cl atom that substitutes into the molecule
      does so at one of the previously chlorinated sites, destroying the aromaticity of
      the ring and altering the molecular properties more dramatically than do the
      first two. The absorbance spectra of Hsp and mono- and di-chlorinated Hsp are all
      very similar and are very distinct from that of trichlorinated Hsp. In
      particular, the latter is the only one of those species that absorbs visible
      light (in a characteristic band centered at approximately 422nm). Di- and
      trichloroHsp form even at low molar Cl/Hsp ratios, and can coexist with Hsp and
      monochloroHsp in neutral, aqueous solutions for at least 24 h in the absence of
      free chlorine. If free chlorine is present, the less-chlorinated species continue
      to acquire Cl, and trichloroHsp undergoes further reaction, until either the free
      chlorine or the trichloroHsp is fully depleted. The appearance of di- and
      trichloroHsp while substantial amounts of Hsp remain unreacted indicates that
      substitution of one or two Cl atoms into the ring facilitates the incorporation
      of yet more Cl into the ring. This autoacceleration of the chlorination process
      is hypothesized to be induced by the increase in acidity that accompanies Cl
      incorporation. Specifically, the increase in the acidity of the phenolic groups
      shifts the equilibrium toward the enolate anion, which is considered to be much
      more amenable to electrophilic attack than the enol.

PMID- 15461170
TI  - Emissions of air pollutants from household stoves: honeycomb coal versus coal
      cake.
AB  - Domestic coal combustion can emit various air pollutants. In the present study,
      we measured emissions of particulate matter (PM) and gaseous pollutants from
      burning a specially formulated honeycomb coal (H-coal) and a coal cake (C-coal).
      Flue gas samples for PM2.5, PM coarse (PM2.5-10), and TSP were collected
      isokinetically using a cascade impactor; PM mass concentrations were determined
      gravimetrically. Concentrations of SO2, NOx, and ionic Cr(VI) in PM were analyzed
      using spectrometric methods. Fluoride concentrations were measured using a
      specific ion electrode method. PM elemental components were analyzed using an X
      ray fluorescence technique. Total (gas and particle phase) benzo[a]pyrene (BaP)
      concentration was determined using an HPLC/fluorescence method. Elemental and
      organic carbon contents of PM were analyzed using a thermal/optical reflectance
      technique. The compositional and structural differences between the H-coal and C
      coal resulted in different emission characteristics. In generating 1 MJ of
      delivered energy, the H-coal resulted in a significant reduction in emissions of
      SO2 (by 68%), NOx (by 47%), and TSP (by 56%) as compared to the C-coal, whereas
      the emissions of PM2.5 and total BaP from the H-coal combustion were 2-3-fold
      higher, indicating that improvements are needed to further reduce emissions of
      these pollutants in developing future honeycomb coals. Although the H-coal and
      the C-coal had similar emission factors for gas-phase fluoride, the H-coal had a
      particle-phase fluoride emission factor that was only half that of the C-coal.
      The H-coal had lower energy-based emissions of all the measured toxic elements in
      TSP but higher emissions of Cd and Ni in PM2.5.

PMID- 15461171
TI  - Adaptation of fugacity models to treat speciating chemicals with constant species
      concentration ratios.
AB  - A "multiplier" method is developed by which multimedia mass balance fugacity
      models designed to describe the fate of a single chemical species can be applied
      to chemicals that exist as several interconverting species. The method is
      applicable only when observed ratios of species concentrations in each phase are
      relatively constant and there is thus no need to define interspecies conversion
      rates. It involves the compilation of conventional transformation and intermedia
      transport rate expressions for a single, selected key species, and then a
      multiplier, Ri, is deduced for each of the other species. The total rate
      applicable to all species is calculated as the product of the rate for the single
      key species and a combined multiplier (1 + R2 + R3 + etc.). The theory is
      developed and illustrated by two examples. Limitations of the method are
      discussed, especially under conditions when conversion rates are uncertain. The
      advantage of this approach is that existing fugacity and concentration-based
      models that describe the fate of single-species chemicals can be readily adapted
      to estimate the fate of multispecies substances such as mercury which display
      relatively constant species proportions in each medium.

PMID- 15461172
TI  - Modeling crude oil droplet-sediment aggregation in nearshore waters.
AB  - This paper describes a modeling approach that simulates changes in particle size
      distribution and density due to aggregation by extending the Smoluchowski
      aggregation kinetic model to particles of different density. Batch flocculation
      studies were conducted for clay, colloidal silica, crude oil, clay-crude oil, and
      silica-crude oil systems. A parameter estimation algorithm was used to estimate
      homogeneous collision efficiencies (alphaHOMO) for single-particle-type systems
      and heterogeneous collision efficiencies (alphaHET) for two-particle-type
      systems. Homogeneous collision efficiency values (alphaHOMO) were greater for
      clay (0.7) and for crude oil (0.3) than for silica (0.01). Thus, clay and crude
      oil were classified as cohesive particles while silica was classified as
      noncohesive. Heterogeneous collision efficiencies were similar for oil-clay (0.4)
      and oil-silica (0.3) systems. Thus, crude oil increases the aggregation of
      noncohesive particles. Data from the calibrated aggregation model were used to
      estimate apparent first-order flocculation rates (K') for oil, clay, and silica
      and apparent second-order flocculation rates (K'') for oil and clay in oil-clay
      systems and for oil and silica in oil-silica systems. For oil or clay systems,
      aggregation Damkohler numbers ranged from 0.1 to 1.0, suggesting that droplet
      coalescence and clay aggregation can occur on the same time scales as oil
      resurfacing and clay settling, respectively. For mixed oil-clay systems, the
      relative time scales of clay settling and clay-oil aggregation were also within
      an order of magnitude. Thus, oil-clay aggregation should be considered when
      modeling crude oil transport in nearshore waters.

PMID- 15461173
TI  - A new method for separating HFC-134a from gas mixtures using clathrate hydrate
      formation.
AB  - A new separation method using gas hydrate formation is proposed for separating
      HFC-134a from gas mixtures containing N2 and HFC-134a. The feasibility of this
      separation method was investigated from various points of view. First, to
      determine the mixed hydrate stability region, three-phase equilibria of hydrate
      (H), liquid water (Lw), and vapor (V) for HFC-134a + N2 + water mixtures with
      various HFC-134a vapor compositions were closely examined in the temperature and
      pressure ranges of 275-285 K and 0.1-2.7 MPa, respectively. Second, the
      compositions of the hydrate and vapor phases at a three-phase equilibrium state
      were analyzed for identical mixtures at 278.15 and 282.15 K to confirm the actual
      separation efficiency. Third, kinetic experiments were performed to monitor the
      composition change behavior of the vapor phase and to determine the time required
      for an equilibrium state to be reached. Furthermore, X-ray diffraction confirmed
      that the mixed HFC-134a + N2 hydrates were structure II. Through an overall
      investigation of the experimental results, it was verified that more than 99 mol
      % HFC-134a could be obtained from gas mixtures after hydrate formation and
      subsequent dissociation processes. Separation of HFC-134a using hydrate formation
      can be carried out at mild temperature and low-pressure ranges. No additive is
      needed to lower the hydrate formation pressure.

PMID- 15461174
TI  - In-line laser holography and video analysis of eroded floc from engineered and
      estuarine sediments.
AB  - Microphytobenthic polymers mediate intertidal sediment erosion processes, through
      biostabilization and modifying the nature of eroded floc material. The latter is
      of key importance with respect to sediment transport dynamics, including floc
      aggregation and particle deposition. In this study, eroded floc material was
      analyzed by video imaging, alongside novel application of in-line laser
      holography (ILH). The erosion of engineered sediment was compared to that of
      natural estuarine sediments. Both video and holography showed an increase in floc
      size eroded from engineered cohesive clay sediment as a function of sediment
      dewatering and sediment polymer content. Estuarine sediment showed a curvilinear
      increase in floc size as a function of both microphytobenthic biomass and
      sediment colloidal polymer content when measured by video analysis. Holography
      did not show these functions for floc size due to temporal limitations of the
      current ILH methodology. An interaction of sediment polymer binding and sediment
      desiccation was observed for engineered sediments and, most notably, for
      estuarine cohesive sediments. In conclusion, engineered sediments were not
      accurate analogues for natural intertidal sediments, failing to reproduce eroded
      floc material similar to that from estuarine cohesive sediment. The size of
      eroded floc from estuarine sediments is a function of the complex interaction
      between biological and physicochemical processes, primarily algal colloidal
      polymer and desiccation. Holography demonstrated an excellent potential for the
      high-resolution imaging of eroded material but is limited by temporal
      constraints; the solution to this would be the development of real-time
      holographic video.

PMID- 15461175
TI  - Compositions and sorptive properties of crop residue-derived chars.
AB  - Chars originating from the burning or pyrolysis of vegetation may significantly
      sorb neutral organic contaminants (NOCs). To evaluate the relationship between
      the char composition and NOC sorption, a series of char samples were generated by
      pyrolyzing a wheat residue (Triticum aestivum L.) for 6 h at temperatures between
      300 degrees C and 700 degrees C and analyzed for their elemental compositions,
      surface areas, and surface functional groups. The samples were then studied for
      their abilities to sorb benzene and nitrobenzene from water. A commercial
      activated carbon was used as a reference carbonaceous sample. The char samples
      produced at high pyrolytic temperatures (500-700 degrees C) were well carbonized
      and exhibited a relatively high surface area (>300 m2/g), little organic matter
      (<3%), and low oxygen content (< or = 10%). By contrast, the chars formed at low
      temperatures (300-400 degrees C) were only partially carbonized, showing
      significantly different properties (<200 m2/g surface area, 40-50% organic
      carbon, and >20% oxygen). The char samples exhibited a significant range of
      surface acidity/basicity because of their different surface polar-group contents,
      as characterized by the Boehm titration data and the NMR and FTIR spectra. The
      NOC sorption by high-temperature chars occurred almost exclusively by surface
      adsorption on carbonized surfaces, whereas the sorption by low-temperature chars
      resulted from the surface adsorption and the concurrent smaller partition into
      the residual organic-matter phase. The chars appeared to have a higher surface
      affinity for a polar solute (nitrobenzene) than for a nonpolar solute (benzene),
      the difference being related to the surface acidity/basicity of the char samples.

PMID- 15461176
TI  - In situ chemical reduction of aquifer sediments: enhancement of reactive iron
      phases and TCE dechlorination.
AB  - In situ chemical reduction of aquifer sediments is currently being used for
      chromate and TCE remediation by forming a permeable reactive barrier. The
      chemical and physical processes that occur during abiotic reduction of natural
      sediments during flow by sodium dithionite were investigated. In different
      aquifer sediments, 10-22% of amorphous and crystalline FeIII-oxides were
      dissolved/reduced, which produced primarily adsorbed FeII, and some siderite.
      Sediment oxidation showed predominantly one FeII phase, with a second phase being
      oxidized more slowly. The sediment reduction rate (3.3 h batch half-life) was
      chemically controlled (58 kJ mol(-1)), with some additional diffusion control
      during reduction in sediment columns (8.0 h half-life). It was necessary to
      maintain neutral to high pH to maintain reduction efficiency and prevent iron
      mobilization, as reduction generated H+. Sequential extractions on reduced
      sediment showed that adsorbed ferrous iron controlled TCE reactivity. The mass
      and rate of field-scale reduction of aquifer sediments were generally predicted
      with laboratory data using a single reduction reaction.

PMID- 15461177
TI  - Activated carbon and tungsten oxide supported on activated carbon catalysts for
      toluene catalytic combustion.
AB  - We have used activated carbon (AC) prepared from almond shells as a support for
      tungsten oxide to develop a series of WOx/AC catalysts for the catalytic
      combustion of toluene. We conducted the reaction between 300 and 350 degrees C,
      using a flow of 500 ppm of toluene in air and space velocity (GHSV) in the range
      4000-7000 h(-1). Results show that AC used as a support is an appropriate
      material for removing toluene from dilute streams. By decreasing the GHSV and
      increasing the reaction temperature AC becomes a specific catalyst for the total
      toluene oxidation (SCO2 = 100%), but in less favorable conditions CO appears as
      reaction product and toluene-derivative compounds are retained inside the pores.
      WOx/AC catalysts are more selective to CO2 than AC due to the strong acidity of
      this oxide; this behavior improves with increased metal loading and reaction
      temperature and contact time. The catalytic performance depends on the
      nonstoichiometric tungsten oxide obtained during the pretreatment. In comparison
      with other supports the WOx/AC catalysts present, at low reaction temperatures,
      higher activity and selectivity than WO, supported on SiO2, TiO2, Al2O3, or Y
      zeolite. This is due to the hydrophobic character of the AC surface which
      prevents the adsorption of water produced from toluene combustion thus avoiding
      the deactivation of the active centers. However, the use of WOx/AC system is
      always restricted by its gasification temperature (around 400 degrees C), which
      limits the ability to increase the conversion values by increasing reaction
      temperatures.

PMID- 15461178
TI  - Reduction of Cr(VI) at a polyaniline film: influence of film thickness and
      oxidation state.
AB  - Hexavalent chromium [Cr(VI)] is highly toxic, carcinogenic, and mutagenic to
      living organisms. In this paper, the reduction of Cr(VI) to the much less toxic
      trivalent state [Cr(III)] was studied at polyaniline films grown to different
      thickness. Much higher rates of Cr(VI) reduction were observed for the "thick"
      polyaniline films. This was explained in terms of the morphology of the polymer
      and the higher surface area of polymer in contact with the Cr(VI) solution. For
      "thin" polyaniline films, the Cr(VI) reduction reaction was found to obey pseudo
      first-order kinetics for the duration of exposure. However, in the case of thick
      polyaniline layers, the Cr(VI) reduction reaction followed a two-stage process,
      with each stage obeying pseudo-first-order kinetics. This was explained in terms
      of oxidation of the polymer from the leucoemeraldine to the emeraldine state and
      then further oxidation of the polymer from the emeraldine to the pernigraniline
      state. Much higher rates of Cr(VI) reduction were observed on oxidation of the
      polymer from the leucoemeraldine to the emeraldine state.

PMID- 15461179
TI  - TCLP underestimates leaching of arsenic from solid residuals under landfill
      conditions.
AB  - Recent revision of the arsenic in drinking water standard will cause many
      utilities to implement removal technologies. Most of the affected utilities are
      expected to use adsorption onto solid media for arsenic removal. The arsenic
      bearing solid residuals (ABSR) from adsorption processes are to be disposed of in
      nonhazardous landfills. The Toxicity Characteristic Leaching Procedure (TCLP)
      tests whether a waste is hazardous or nonhazardous; most solid residuals pass the
      TCLP. However, the TCLP poorly simulates the alkaline pH, low redox potential,
      biological activity, long retention time, and organic composition of mature
      landfills. These same conditions are likely to favor mobilization of arsenic from
      metal oxide sorbents. This study quantifies leaching of arsenic from Activated
      Alumina (AA) and Granular Ferric Hydroxide (GFH), two sorbents expected to be
      widely used for arsenic removal. The sorbents were subjected to the TCLP, the
      Waste Extraction Test (WET), an actual landfill leachate, and two synthetic
      leachate solutions. Up to tenfold greater arsenic concentration is extracted by
      an actual landfill leachate than by the TCLP. Equilibrium leachate concentrations
      are not achieved within 18 h (the TCLP duration) and an N2 headspace and end-over
      end tumbling increase the rate of arsenic mobilization. However, tests with
      actual landfill leachate indicate the WET may also underestimate arsenic
      mobilization in landfills.

PMID- 15461180
TI  - Organic fouling and chemical cleaning of nanofiltration membranes: measurements
      and mechanisms.
AB  - Fouling and subsequent chemical cleaning of nanofiltration (NF) membranes used in
      water quality control applications are often inevitable. To unravel the
      mechanisms of organic fouling and chemical cleaning, it is critical to understand
      the foulant-membrane, foulant-foulant, and foulant-cleaning agent interactions at
      the molecular level. In this study, the adhesion forces between the foulant and
      the membrane surface and between the bulk foulant and the fouling layer were
      determined by atomic force microscopy (AFM). A carboxylate modified AFM colloid
      probe was used as a surrogate for humic acid, the major organic foulant in
      natural waters. The interfacial force data were combined with the NF membrane
      water flux measurements to elucidate the mechanisms of organic fouling and
      chemical cleaning. A remarkable correlation was obtained between the measured
      adhesion forces and the fouling and cleaning behavior of the membrane under
      various solution chemistries. The AFM measurements further confirmed that
      divalent calcium ions greatly enhance natural organic matter fouling by
      complexation and subsequent formation of intermolecular bridges among organic
      foulant molecules. Efficient chemical cleaning was achieved only when the calcium
      ion bridging was eliminated as a result of the interaction between the chemical
      cleaning agent and the fouling layer. The cleaning efficiency was highly
      dependent on solution pH and the concentration of the chemical cleaning agent.

PMID- 15461181
TI  - PCDD/F TEQ indicators and their mechanistic implications.
AB  - Stack gas samples from two incinerator facilities with different operating
      conditions were investigated to understand how indicators of toxic equivalency
      (TEQ) from among the 210 polychlorinated dibenzo-p-dioxin/furan (PCDD/F) isomers
      varied. This effort was motivated by the need to find more easily monitored
      indicator compound(s) of TEQ and to reconcile the varying indicator compounds
      reported in the literature. The measured isomer patterns were compared with those
      expected from known formation mechanisms to identify the dominant mechanism(s)
      and explain why certain compounds are relevant TEQ indicators. Despite
      differences in the facility types and operating conditions, a common pattern was
      found for the highly chlorinated (4Cl and higher) PCDDs/Fs. A combination of
      chlorination/dechlorination reactions as the dominant formation mechanism for
      PCDF was consistent with the observed isomer patterns, whereas condensation
      reactions of phenolic precursors appeared to be responsible for PCDD formation.
      PCDF isomers, ratherthan the PCDD isomers, were more closely related to the TEQ
      measure, likely because the chlorination mechanism favors 2,3,7,8-Cl-substitution
      more than the phenol condensation mechanism. Unlike highly chlorinated PCDD/F
      isomer patterns, less chlorinated PCDD/F patterns (especially, mono- and di-CDF)
      were sensitive to operating conditions and facility type. Competing formation
      mechanisms were inferred from the variation of observed isomer distribution
      patterns; this sensitivity resulted in relatively low correlations of these
      isomers with PCDD/F TEQ values. This suggests that any use of the low-chlorinated
      compounds as TEQ indicators for online monitoring processes are likely best
      suited for plant-specific, rather than universal, applications. In addition to
      many of the highly chlorinated (penta-CDF, hexa-, and heptaCDD/F) isomers being
      identified as strong TEQ indicators, 1 of 12 (8%), 5 of 17 (29%), and 5 of 28
      (18%) of the separable tri-CDD, tri-CDF, and tetra-CDF isomers, respectively,
      were identified as strong (R2 > 0.7) TEQ indicators in both incinerators.

PMID- 15461182
TI  - Comment on "Critical evaluation of desorption phenomena of heavy metals from
      natural sediments".

PMID- 15461183
TI  - Properties of phospholipid monolayer deposited on a fluorinated polyurethane.
AB  - A simple procedure for surface modification of polyurethane by the Langmuir
      Blodgett (LB) method using the amphiphile 1,2-distearoyl-sn-glycero-3
      phosphocholine dihydrate (DSPC) was developed. The polyurethane containing the
      fluorinated moiety was prepared via the perfluoro-containing chain extender
      2,2,3,3-tetrafluoro-1,4-butanediol. The fluorinated polyurethane (FPU) films were
      prepared by spin coating and dipping methods. The spin-coated FPU films exhibited
      hydrophobic characteristic and, thus, enhanced the transferability of DSPC. Held
      at constant pressure of 45 mN/m, the DSPC monolayer was transferred successfully
      to FPU films with a near-unity transfer ratio. The in vitro platelet adhesion
      assay revealed that the FPU modified with DSPC monolayer was more platelet
      compatible than the unmodified FPU substrates with no pseudopods and flattening
      of adherent platelets as well as lower platelet adhesion density. Moreover, the
      DSPC monolayer remained intact after platelet adhesion testing. In addition, the
      platelet compatibility of the unmodified FPU was affected by the film preparation
      methods. This might be attributed to the distinctive surface micromorphology
      formed. This simple DSPC deposition scheme by a LB technique would be very useful
      to further enhance the platelet compatibility of hydrophobic substrate and can be
      utilized for biomedical application in which the flow shear rate is not too high.

PMID- 15461184
TI  - Sulfation of silk sericin and anticoagulant activity of sulfated sericin.
AB  - Silk sericin extracted from a cocoon was sulfated by chlorosulfonic acid.
      Sulfation of sericin was confirmed by FT-IR and the reaction efficiency was
      calculated as 44.9%. 1H-NMR suggested that sulfation mainly occurred at serine
      residues in the sericin molecule. The sulfated sericin was separated in three
      fractions by gel-filtration chromatography using Sephacryl S-200. The sulfate
      group content and amino-acid composition of each fraction were almost identical,
      while the anticoagulant activity differed for each fraction of sulfated sericin.
      Higher anticoagulant activity was observed for the higher-molecular-mass
      fraction. The anticoagulant activity of sulfated sericin was estimated at 1/10 to
      1/20 of heparin.

PMID- 15461185
TI  - Cellulose acetate hollow fiber membranes blended with phospholipid polymer and
      their performance for hemopurification.
AB  - Commercially available hollow fiber membranes (HFMs) made from synthetic
      polymers, including cellulose acetate (CA) HFMs, used as hemopurification
      membranes, need to improve in hemocompatibility, by suppressing protein
      adsorption and clot formation. In this study, CA HFMs blended with 2
      methacryloyloxyethyl phosphorylcholine (MPC) copolymer (PMB30 composed of MPC and
      n-butyl methacrylate (BMA)) were prepared by a dry-jet wet spinning process.
      Their performances were evaluated by characterizing their properties such as
      structure, permeability and protein adsorption. CA/PMB30-blend HFMs showed
      structure changes such as increase of porosity, development of large pores and
      decreasing of the thickness of the active layer. And the structure and
      permeability of CA/PMB30-blend HFMs were controllable by changing preparation
      conditions. Also, the CA/PMB30-blend HFMs had good permeability, low protein
      adsorption and low fouling property during the permeability experiment in
      comparison with CA HFMs, because the hydrophilic and hemocompatible MPC copolymer
      (PMB30) existed on the surface of the HFM.

PMID- 15461186
TI  - Macroporous biodegradable natural/synthetic hybrid scaffolds as small intestine
      submucosa impregnated poly(D,L-lactide-co-glycolide) for tissue-engineered bone.
AB  - Poly(D,L-lactide-co-glycolide) (PLGA), a biodegradable synthetic polymer, is
      widely used in a variety of tissue-engineered applications, including drug
      delivery systems. However, the PLGA scaffolds, macroporous and three-dimensional
      structure, are difficult to cell attachment and in-growth due to surface
      hydrophobicity. In order to introduce in new bioactive functionality from porcine
      small intestine submucosa (SIS) as natural source for PLGA, we fabricated SIS
      powder-impregnated PLGA (SIS/PLGA) hybrid scaffolds. Fabrication parameters,
      including ratios of SIS, PLGA and salt, were optimized to produce the desired
      macroporous foam. The scaffolds had a relatively homogeneous pore structure, good
      interconnected pores from the surface to core region and showed an average pore
      size in the range 69.23-105.82 microm and over 90% porosity. The SIS/PLGA
      scaffolds degraded with a rate depending on the contents of the SIS. After the
      fabrication of the SIS/PLGA hybrid scaffolds the wettability of the scaffold was
      greatly enhanced, resulting in uniform cell seeding and distribution. So, it was
      observed that BMSC attachment to the SIS/PLGA scaffolds increased gradually with
      increasing SIS contents. Scaffolds of PLGA alone and SIS/PLGA were implanted
      subcutaneously under dorsal skin of athymic nude mouse to observe the
      osteoconductivity. It was found from the result that the effects of the SIS/PLGA
      scaffolds on bone formation are stronger than control PLGA scaffolds. In summary,
      the SIS/PLGA scaffolds have osteoconductive effects to allow remodeling and
      replacement by osseous tissue.

PMID- 15461187
TI  - Bioadhesion and biocompatibility evaluations of gelatin and polyacrylic acid as a
      crosslinked hydrogel in vitro.
AB  - This study describes the potentiality of crosslinked hydrogels comprised of
      gelatin and polyacrylic acid (CHGP) as a biological glue for soft tissues and
      compares its bonding strength with that of fibrin glue. Water-soluble carbodimide
      (WSC) was used to crosslink the mixture of gelatin and polyacrylic acid (PAA). An
      addition of PAA to gelatin increases bonding strength and reduces the gelation
      time and WSC concentration. Increasing the gelatin, WSC and PAA concentration
      increases the bonding strength. There is a critical concentration to have a
      maximum bonding strength. The cured hydrogel exhibited sufficient adhesion to
      mouse skin with a higher bonding strength than fibrin glue. The in vitro test has
      been done for evaluating CHGP toxicity.

PMID- 15461188
TI  - Plasma synthesis of carbon magnetic nanoparticles and immobilization of
      doxorubicin for targeted drug delivery.
AB  - Using dense medium plasma technology, carbon magnetic nanoparticles (CMNP) were
      synthesized at room temperature and atmospheric pressure. Based on results from X
      ray photoelectron spectroscopy, Fourier transform infrared spectroscopy and
      scanning electron microscopy, we conclude that these nanoparticles are composed
      of spherical particles, 40-50 nm in diameter, with iron/iron oxide particles
      dispersed in a carbon-based host-structure. Thermal gravimetry/differential
      thermal gravimetry analysis shows these nanoparticles are stable to temperatures
      as high as 600 degrees C. The synthesized CMNP were treated by argon-plasma,
      aminated with ethylene diamine and subsequently activated by generating aldehyde
      groups on them. Free doxorubicin (DOX) molecules were then immobilized onto the
      surfaces of activated CMNP particles to form CMNP-DOX conjugates. The
      corresponding loading efficiency was determined. The in vitro antiproliferative
      activity of immobilized doxorubicin in the conjugates was demonstrated in tumor
      cell cytotoxicity assays. It is suggested that this CMNP-DOX system can be used
      for targeted drug-delivery systems.

PMID- 15461189
TI  - Serum protein adsorption and platelet adhesion on aspartic-acid-immobilized
      polysulfone membranes.
AB  - Polysulfone (PSf) membranes that covalently conjugated with aspartic acid (ASP
      PSf) were prepared and analyzed for hemocompatability. Compared to PSf or other
      types of surface-modified PSf membranes, the ASP-PSf membranes had a reduced
      ability to adsorb protein from either a plasma solution or a mixed solution of
      albumin, globulin and fibrinogen. This appears to be due to the creation of a
      hydrophilic surface by the aspartic acid zwitterion immobilized on the ASP-PSf
      membranes. Furthermore, the analyses of membrane protein adsorption showed that a
      mixed protein solution recapitulates the cooperative adsorption of proteins that
      occurs in plasma. We also found that the number of adhering platelets was the
      lowest on the ASP-PSf membranes and, in general, that platelet adhesion decreased
      in parallel with fibrinogen adsorption. In summary, aspartic acid immobilized on
      the ASP-PSf membranes, which have zwitterions with a net zero charge, effectively
      contributes to the hydrophilic and hemocompatible sites on the surface of the
      hydrophobic PSf membranes.

PMID- 15461190
TI  - Synthesis and characterization of thermosensitive chitosan copolymer as a novel
      biomaterial.
AB  - Novel water-soluble thermosensitive chitosan copolymers were prepared by graft
      polymerization of N-isopropylacrylamide (NIPAAm) onto chitosan using cerium
      ammonium nitrate (CAN) as an initiator. The physicochemical properties of the
      resulting chitosan-g-NIPAAm copolymers were characterized by Fourier transform
      infrared (FT-IR) spectroscopy, 1H-nuclear magnetic resonance, X-ray diffraction
      measurement, thermogravimetric analysis (TGA) and solubility test. Sol-gel
      transition behavior was investigated by the cloud point measurement of the
      chitosan-g-NIPAAm aqueous solution. The gelling temperature was examined using
      the vial inversion method. The percentage of grafting (%) and efficiency of
      grafting (%) were investigated according to concentrations of monomer and
      initiator. The maximum grafted chitosan copolymer was obtained with 0.4 M NIPAAm
      and 6 x 10(-3) M CAN. Water-soluble chitosan-g-NIPAAm copolymers were prepared
      successfully and they formed thermally reversible hydrogel, which exhibits a
      lower critical solution temperature (LCST) around 32 degrees C in aqueous
      solutions. A preliminary in vitro cell study showed nontoxic and biocompatible
      properties. These results suggest that chitosan-g-NIPAAm copolymer could be very
      useful in biomedical and pharmaceutical applications as an injectable material
      for cell and drug delivery.

PMID- 15461191
TI  - Evaluation of community based injury prevention: an epidemiologist's quandary.

PMID- 15461192
TI  - Effectiveness of interventions in the prevention of childhood obesity.
AB  - The prevalence of childhood obesity, as with that of adulthood, has increased
      considerably over the past few years and has become a serious public health
      problem. Once established, its treatment is very difficult and, hence, prevention
      of childhood obesity using different types of intervention appears promising. The
      objective of this present report is to review interventions that had been
      conducted over the past 11 years in the environment of the family, schools and
      community, and directed towards the prevention of childhood obesity. We reviewed
      the different strategies employed, the different criteria used in defining weight
      status, the evaluation and follow-up methods, and the degree of effectiveness.
      Benefits other than reduced weight gain were assessed, as well. In our review, we
      selected 14 intervention studies. The differences in design, duration and outcome
      assessments make direct comparison difficult. Nevertheless, it seems that
      nutritional education and promotion of physical activity together with behaviour
      modifications, decrease in sedentary activities and the collaboration of the
      family could be the determining factors in the prevention of childhood obesity.
      Other important benefits regarding healthy habits apart from the changes in
      weight status were pursued in the majority of the studies reviewed. The need for
      well-designed studies that examine a range of interventions remains a priority.

PMID- 15461193
TI  - Estimating non-response bias in family studies: application to mental health and
      lifestyle.
AB  - Non-response to mailed surveys reduces the effective sample size and may
      introduce bias. Non-response has been studied by (1) comparison to available data
      in population based registers, (2) directly contacting non-respondents by
      telephone or single-item reply cards, and (3) longitudinal repetition of the
      survey. The goal of this paper was to propose an additional method to study non
      response bias: when the variable of interest has a familial component, data from
      respondents can be used as proxy for the data from their non-responding family
      members. This approach was used with data on smoking, alcohol consumption,
      physical activity, coffee- and tea-use, education, body mass index, religion,
      burnout, life events, personality and mental health in large number of siblings
      and DZ twins registered with the Netherlands Twin Register. In addition, for
      smoking behavior, we also used the second strategy by sending a reply card.
      Results show that scores of members from less cooperative families or incomplete
      twin pairs tended to be more unfavorable than the scores from highly cooperative
      families or complete twin pairs. For example, family members from less
      cooperative families cycled less often and scored higher on anxious depression
      and neuroticism. For smoking, both the results of the reply card and the results
      of the additional method suggested a higher percentage smokers among the non
      respondents but this was only significant with reply card method. In general,
      differences between highly/less cooperative families and complete/incomplete DZ
      twins were small. Results suggest that, even for studies with moderate response
      rates, data collected on health, personality and lifestyle are relatively
      unbiased.

PMID- 15461194
TI  - Psychosocial working conditions and the risk of esophageal and gastric cardia
      cancers.
AB  - BACKGROUND: For reasons yet unknown, the incidence of esophageal and gastric
      cardia adenocarcinoma is increasing rapidly and moderately, respectively. These
      tumors occur predominantly among males. We hypothesized that stressful
      psychosocial working conditions might be involved in the etiology of these
      cancers. OBJECTIVE: To study if job strain, work pace satisfaction and coping are
      linked to the risk of esophageal or cardia cancers. METHODS: A nationwide Swedish
      population-based case-control study including 189 and 262 esophageal and cardia
      adenocarcinoma cases, respectively, 167 esophageal squamous-cell carcinoma cases,
      and 820 controls. All study subjects were interviewed. The relative risk was
      estimated using odds ratios, with 95% confidence intervals, adjusted for
      potential confounders. RESULTS: We found no statistically significant
      associations between two different measures of job strain and the three cancer
      types, except between one job strain measure and risk of cardia adenocarcinoma
      (OR: 2.2; 95% CI: 1.0-4.8). There was a moderately strong association between
      having a covert coping style, compared to an overt, and risk of both esophageal
      (OR: 1.8; 95% CI: 1.2-2.8) and cardia adenocarcinoma (OR: 1.5; 95% CI: 1.0-2.3).
      Among subjects reporting low work pace satisfaction we found an almost 4-fold
      increased risk of esophageal squamous-cell carcinoma (OR: 3.8; 95% CI: 1.3-11.0),
      and a nearly 3-fold increased risk of esophageal adenocarcinoma (OR: 2.8; 95% CI:
      1.1-7.0). CONCLUSIONS: Work-related stress does not seem to be of importance in
      the etiology of adenocarcinoma of the esophagus or the gastric cardia. However,
      the interaction of a stressful work environment and the individual's responses to
      it may be associated with a moderately increased risk of these cancer types.

PMID- 15461195
TI  - Socio-economic level, farming activities and risk of cancer in small areas of
      Southern Spain.
AB  - An ecological design was used to study the relationship between cancer incidence
      and both socioeconomic and environmental features in Southern Spain. Twenty-four
      sites and 26,380 cases diagnosed in 1985--1996 were analysed. Generalised
      Additive Models were used for data analysis. Except for lip cancer, the urban
      areas showed an increase in cancer risk for all sites. The relative risks among
      urban and rural municipalities ranges between 1.09 for skin non-melanoma (95% CI:
      1.00-1.18) and 1.64 for cervix cancer (95% CI: 1.28-2.12). The relative risk
      among areas with high and low unemployment was 1.29 for stomach cancer (95% CI:
      1.07-1.57), 1.45 for oral cavity cancer (95% CI: 1.10-1.93) and 1.77 for
      oesophagus cancer (95% CI: 1.02-3.05). Areas with highest unemployment showed the
      lowest incidence of melanoma. Risk for leukaemia, gall bladder, breast and
      prostate cancer showed a significant decreases by approximately 28% in the
      municipalities with the highest illiteracy score. A high percentage of land under
      cultivation was related to uterine tumours, larynx, rectum, lung, skin non
      melanoma and brain cancers. For these sites, the risk had a significant increase
      by between 23% (skin non-melanoma) and 70% (rectum). Areas with high intensive
      farming showed a significant increase in cancer risk for lip, oral cavity,
      larynx, oesophagus, colon, lung, and bladder cancer. The relative risks ranges
      between 1.16 for colon cancer (95% CI: 1.04-1.29) and 1.47 for oesophagus cancer
      (95% CI: 1.15-1.87). The results of this study reveal how important socio
      economic and environmental factors are for the analysis of cancer incidence in
      small areas of Southern Spain.

PMID- 15461196
TI  - Apolipoprotein E genotype frequency patterns in aged Danes as revealed by
      logistic regression models.
AB  - Although the ApoE gene has been intensively studied in aging research, most of
      the studies conducted so far have been based on the traditional case-control
      design with subjects consisting of young controls and long-lived cases. The
      genotype frequency pattern in and between the two age-groups has been rarely
      investigated due to limitations in either research design or data analytical
      method. In this study, we genotyped 748 individuals (including both twin pairs
      and unrelated individuals) aged from 73 to 95 with aim at examining the genotype
      frequency trajectory of ApoE gene at high ages. Binomial and multinomial logistic
      regression models have been applied to model the gene frequency as a function of
      age and to investigate the modes of gene function (dominant, recessive,
      additive). The generalized estimation equations (GEEs) are introduced to account
      for the intra-pair genotype correlation in the twin pairs included in the data.
      Both the observed and the fitted frequencies show a constantly declining pattern
      of ApoE epsilon4 allele as age advances indicating a significant and steadily
      deleterious effect of the dominant allele that increases the hazard of death at
      high ages.

PMID- 15461197
TI  - Waist circumference and testosterone levels in community dwelling men. The Tromso
      study.
AB  - To examine the relationship of total and free testosterone and sex hormone
      binding globulin (SHBG) with central obesity in men, we studied 1548 men aged 25
      84 years that took part in the 1994--1995 survey of the Tromso study. Total
      testosterone and SHBG were measured by immuno-assay and the free testosterone
      fraction was calculated. These measurements were analyzed in relation to
      anthropometric data and lifestyle factors. The age-adjusted correlation between
      waist circumference (WC) and total testosterone was -0.34 (p < 0.001), between WC
      and free testosterone -0.09 (p < 0.001) and, between WC and SHBG -0.44 (p <
      0.001). Adjusting for BMI and lifestyle factors weakened, but did not eliminate
      these associations. All hormone and SHBG associations were stronger for WC than
      for waist-hip ratio or BMI. In age- and BMI-adjusted analyses men with a WC > or
      = 102 cm had significantly lower levels of total testosterone and SHBG compared
      to men with an optimal WC, defined as < 94 cm (12.3 vs. 13.9 nmol/l; p < 0.01 and
      48.5 vs. 55.1 nmol/l; p < 0.001, respectively). The lowest levels of total and
      free testosterone were observed in men with relatively high WC despite relatively
      low overall obesity (BMI), suggesting that WC should be the preferred
      anthropometric measurement in predicting endogenous testosterone levels.

PMID- 15461198
TI  - Prevalence, types and possible causes of insomnia in a Swiss remand prison.
AB  - STUDY OBJECTIVES: To determine the prevalence of insomnia complaints and possible
      causes among prisoners. DESIGN: Prospective study of medical consultations during
      1 year (questionnaire A) to identify reasons for consultation and diagnoses.
      After this year we compared the medical records (questionnaire B) of 112 non
      substance misusing (NSM) insomniac prisoners identified through questionnaire A
      with the records of 103 NSM prisoners without insomnia complaint. SETTING:
      Outpatient service of the remand prison in Geneva, Switzerland. PATIENTS: 995
      prisoners. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The general
      practitioners returned completed questionnaires A for 92% (n = 2772) of the
      consultations (995 patients). Using questionnaire A and B, we identified 112 NSM
      insomnia patients. Among these, chronic forms of insomnia were more common than
      transitory insomnia (<3 weeks). The most frequently reported reason for insomnia
      was anxiety related to incarceration. A higher percentage of the 112 insomnia
      patients than of the 103 non-insomnia patients had a history of medical and
      psychiatric illness, suffered from anxiety or depression in prison, and received
      prescriptions of psychotropic and analgesic medications. After the study of the
      records, we estimated the overall prevalence of insomnia at 44.3% of the 995
      patients of whom 51% (n = 223) were drug misusers. CONCLUSIONS: Our results
      confirm that insomnia is a frequent complaint among prisoner patients and that at
      least half of insomnia patients are substance misusers. In NSM patients, insomnia
      does not seem to be an only transitory problem of adaptation to incarceration,
      but a more chronic problem lasting more than 3 weeks, related to a higher degree
      of medical and psychological problems before and during incarceration.

PMID- 15461199
TI  - Ethnic differences in reported smoking behaviors in face-to-face and telephone
      interviews.
AB  - Different modes of gathering data on self-reported health measures and self
      reported risk factors are used frequently in research. However, data on the
      influence of the mode of collection of data on self-reporting are limited. The
      aim of the study was to identify associations between the mode of data collection
      and self-reported smoking in two distinct ethnic groups, Jews and Arabs in
      Israel. During the last 2 years, data were collected in two national surveys
      regarding the smoking behaviors of Jews and Arabs in Israel. In the telephone
      surveys 4713 Israeli residents were interviewed and in the face-to-face
      interviewees 3239 people were interviewed. The interviewees were between the ages
      25 and 64. There was no significant difference in smoking rates between face-to
      face interviews and telephone interviews among Jewish men or women after
      adjusting for other variables associated with smoking. However, there was a
      difference between the two methods of data collection in the Arab population also
      after the adjustment. In this group, respondents tended to report more often
      being a smoker in the face-to-face interviews. This was especially apparent in
      Arab women. There was no significant difference in the reported number of
      cigarettes smoked in the two modes of data collection. In Arabs compared to Jews
      there is a significant difference between reporting smoking during a telephone
      interview and a face-to-face interview. The mode of data collection can affect
      comparisons between different groups.

PMID- 15461200
TI  - Osteoarthritis of the hands in the rural population: a follow-up study.
AB  - The aim of this study was to analyze the progression of hand osteoarthritis in
      rural population and to determine the factors which could influence that
      progression. Participants of both sexes were 54-56 years of age at the first
      visit. Radiographs of both hands, anthropometry and blood pressure measurement
      were performed at baseline and than repeated 10 years later. Total number of 286
      participants completed the study. Radiographs were red according to Kellgren
      Lawrence criteria. Distal interphalangeal (DIP) joints were most frequently
      affected with osteoarthritis at the baseline and after 10 years. The worst
      deterioration (three grades) was found in DIP joints in women and in proximal
      interphalangeal joints in men. Grip strength in men was significantly related
      with progression of the disease, which allow us to conclude that in our
      population sample mechanical factors, probably occupational workload, are
      associated with the more rapid progression of the disease.

PMID- 15461201
TI  - Two years of a fungal aerobiocontamination survey in a Florentine haematology
      ward.
AB  - The control of microbial air contamination in hospital wards has assumed great
      importance particularly for those hospital infections where an airborne infection
      route is hypothesised, such as aspergillosis. Invasive aspergillosis represents
      one of the most serious complications in immunocompromised patients. For some
      authors there is a direct association between this pathology and the
      concentrations of Aspergillus conidia in the air; in addition, reports of
      aspergillosis concurring during building construction have been frequent. In this
      study, two haematology wards were monitored for about 2 years in order to make
      both a qualitative and quantitative evaluation of fungal burden in the air, also
      in relation to major construction and demolition work taking place in the same
      building. Air samples were taken from the hospital rooms of neutropenic patients,
      in the corridors of their ward and outside the building. Total fungal
      concentration resulted higher outside (mean 572 Colony Forming Units/m3 of air),
      lower in the corridors (147 CFU/m3) and even lower in the rooms (50 CFU/m3). In
      all the samples we found the development of at least one fungal colony.
      Cladosporium was the most frequently isolated genus (57%), in contrast to
      Aspergillus spp. (2%). The average concentration of Cladosporium spp. was 24
      CFU/m3 in the rooms, 78 CFU/m3 in the corridors and 318 CFU/m3 outside. The
      average concentration of Aspergillus spp. was 1.2 CFU/m3 in the rooms, 3.5 CFU/m3
      in the corridors, 5.6 CFU/m3 outside. Our observations show low concentrations of
      Aspergillus fumigatus and A. flavus in all the environments examined and
      particularly in the rooms (0.09 and 0.10 CFU/m3 respectively); this observation
      could explain the absence of cases of invasive aspergillosis during the period of
      air monitoring in the two haematology wards.

PMID- 15461202
TI  - The burden of severe varicella in Spain, 1995--2000 period.
AB  - BACKGROUND: Population-based estimates of hospitalization rates for varicella
      provide data of the severe and costly end of this disease. OBJECTIVE: To estimate
      the annual burden of hospitalization due to primary varicella in the 17
      Autonomous Regions of Spain. METHODS: Data were obtained from the national
      surveillance system for hospital data and comprises all hospital discharges for
      varicella reported during the 1995--2000 period. RESULTS: The overall incidence
      of hospitalizations was 2.7 per 100,000 persons per year (ranging from 3.2 in
      Navarra to 1.5 in the Canary Islands). Forty-eight deaths were reported during
      the period. Each year varicella was responsible for 3017 days of hospitalization
      in persons < or =10 years of age and 3333 days in persons > 10 years of age. The
      annual cost of these hospitalizations was 1.2 million and more than 500.000 euros
      for persons < or =10 years and > 10 years of age, respectively. CONCLUSION:
      Varicella is associated to a severe morbidity in children, adolescents and adults
      in Spain. The burden of varicella is likely to be potentially reduced by
      effective immunization programs.

PMID- 15461203
TI  - Antibiotic treatment for influenza does not affect resolution of illness,
      secondary visits or lost workdays.
AB  - Antibiotics are common prescribed against influenza, although no trials of their
      efficacy have been published. We compared clinical and societal outcomes in 701
      patients (56% flu-positive) according to use of antibiotics. The median duration
      of illness, rate of secondary visits, and lost workdays did not differ between
      antibiotic and non-antibiotic treated patients. Antibiotics are unnecessary
      expenses in the initial treatment of influenza, as they can give potential side
      effects and contribute to spread of antibiotic-resistant bacteria.

PMID- 15461204
TI  - The incidence of infectious diseases and changes in the mortality of
      atherosclerosis-related complications in the Czech population over the past two
      decades.

PMID- 15461205
TI  - The role of cancer registration in National Cancer Control Pakistan.

PMID- 15461206
TI  - Comparison of optimal malarial test with light microscopy for the diagnosis of
      malaria.
AB  - OBJECTIVE: To evaluate the efficacy of a parasite lactate dehydrogenase-based
      immunochromatographic antigen detection assay (optimal) against conventional
      light microscopy in the diagnosis of malaria at Military Hospital, Rawalpindi and
      Department of Pathology Army Medical College Rawalpindi from August to October
      2002 in patients reporting sick with history suggestive of malaria. METHODS: The
      blood samples were collected from 215 patients reporting with symptoms suggestive
      of malaria. Thick and thin blood films were prepared, stained with Leishman's
      stain and examined by light microscopy for the presence of malarial parasites.
      Parasitaemia was estimated on all positive slides. All samples were tested for
      presence of malarial parasite by optimal dipstick method according to the
      manufacturer's instructions. RESULTS: A total of 215 cases were studied. Malarial
      parasites were visualized in 98 (45.5%) cases with light microscopy. Optimal test
      revealed 93 (43.2%) of these samples as positive. Microscopy showed 61 out of 98
      positive cases to be P. vivax and 37 P. falciparum. The Optimal dipstick method
      revealed that 58 out of 93 were positive for P. vivax and 35 positive for P.
      falciparum. These results demonstrated that Optimal had sensitivities of 95% and
      94.5% for P. vivax and P. falciparum respectively. It has 100% specificity for
      both malarial species, when compared to conventional microscopy. CONCLUSION:
      Optimal test showed excellent correlation with microscopy in the diagnosis of P.
      vivax and P. falciparum. It is expensive but it has an advantage of being simple,
      rapid and effective test in the diagnosis of malaria especially where well
      trained microscopists are not available or work load is too high.

PMID- 15461207
TI  - Risk factors for clinical infection in patients colonized with methicillin
      resistant Staphylococcus aureus (MRSA).
AB  - OBJECTIVE: To identify the risk factors involved in development of infection in
      individuals colonized with Methicillin-resistant Staphylococcus aureus (MRSA)
      among intensive care unit (ICU) patients. METHODS: A total of 1431 patients were
      admitted in ICU of which 63 grew MRSA during January 1998 to December 1999.
      Patients who developed infection with MRSA in less than 48 hours of their
      admission to ICU were excluded. Medical records of all patients who grew MRSA
      were reviewed and 57 patients were identified for inclusion in the study. Thirty
      seven of these had features of infection with MRSA and were selected as cases and
      20 were identified as asymptomatic colonizers and labeled as controls. Risk
      factors like age of the patient, duration of ICU stay, gender, co-morbidity,
      presence and duration of central lines, number of arterial-punctures and number
      and duration of intubations were compared between cases and controls. RESULTS:
      Cases were found to be significantly older (52.8 +/- 15.1) than controls (34.9 +/
      21.2). Other identified risk factors were diabetes mellitus (p = 0.001) and the
      first 15 days of central line placement (p = 0.025). Although chronic liver
      disease and hypertension could not be identified as significant risk factors,
      they clearly showed association. Other risk factors were not significantly
      different from controls. CONCLUSION: It is suggested that greater care is
      required for the elderly, diabetic patients with a central venous line in place
      especially during the first fifteen days of its introduction.

PMID- 15461208
TI  - Prevalence of pulmonary tuberculosis in Karachi central prison.
AB  - OBJECTIVE: To determine the extent of pulmonary tuberculosis among prisoners in
      Karachi central jail, so that strategy for targeted intervention can be planned.
      METHOD: This prospective observational study was done at Karachi central prison
      from 7-2-2002 to 14-2-2002. A team of doctors, laboratory and x-ray technicians
      visited the central prison. Patients who had symptoms suggestive of pulmonary
      tuberculosis were included in the study. Their chest x-ray was taken in the jail
      and three "spot specimens" of sputum were collected for three consecutive days.
      The sputum specimens were processed at the laboratory of Ojha Institute of Chest
      Diseases, Karachi. RESULTS: Out of 4870 prisoners, 79 (1.62%) were pulmonary
      tuberculosis suspects. All were male and their mean age was 32 (22-75) years.
      Sixteen suspects already diagnosed were on anti-tuberculosis treatment (ATT)
      while 11 suspects gave history of ATT in the past for incomplete duration varying
      from 3-4 weeks to 3 months either regularly or irregularly. Twenty-two (28%)
      suspects were not expectorating while fifty-seven (72%) submitted the sputum for
      AFB (Acid Fast Bacilli), of which only one was smear positive. Radiologically, 39
      (49%) chest x-rays including those of 22 who were not expectorating were normal.
      Eight (10%) showed healed lesion. Thirty-two (40.5%) chest x-rays were suggestive
      of active pulmonary tuberculosis, so clinically and radiologically 32 prisoners
      were suffering from active pulmonary tuberculosis. The prevalence of active
      pulmonary tuberculosis in jail population determined by using the formula, number
      of persons with active TB in jail divided by the total number of persons booked
      into jail was 657 per 100,000, which is 3.75 times higher than general
      population. CONCLUSION: Pulmonary tuberculosis is 3.75 times more common than
      general population in Karachi central prison and concrete efforts are needed to
      eradicate tuberculosis from this segment of population. The integration of
      provincial TB control program with that of jail health services is urgently
      required.

PMID- 15461209
TI  - Morphological study of liver biopsy in Thalassaemia major.
AB  - OBJECTIVE: To see the morphological changes in liver in transfusion dependent
      Thalassaemia major children undergoing bone marrow transplantation. METHODS: This
      retrospective cross-sectional survey was conducted at Pathology department of
      Army Medical College and Paediatric department of Military Hospital, Rawalpindi
      from Jul 2000 to Aug 2003. Liver biopsies were done in 40 thalassaemic major
      children and histological changes including Knodell Histological activity index
      (HAI); grade, stage and score along with degree of haemosiderosis were noted.
      Serum ALT levels, ferritin assays and screening for HBsAg and Anti- HCV antibody
      were also carried out in these cases. RESULTS: Forty children 1.5-10.5 years of
      age (mean 6.1 years) with a male to female ratio of 1.2:1 were included in the
      study. According to Knodell HAI scoring, 24 (60%) cases had Knodell HAI score
      between 13/22 to 18/22 and 18 patients (45%) in grade 9-12/18. Six children had
      fully developed cirrhotic changes whereas 22 and 12 patients showed stage 3 and 1
      respectively. Twenty eight (70%) patients had grade 3-4 haemosiderosis. HBsAg was
      positive in 6 and anti- HCV antibody in 14 patients. Serum ferritin and ALT
      levels were markedly raised in most of the patients. CONCLUSION: Seventy percent
      patients had moderate to severe haemosiderosis and high Knodell HAI score was
      found in children with severe haemosiderosis, raised ALT and Ferritin levels and
      with positive serology for HBsAg and anti- HCV antibody. Liver biopsy is useful
      in thalassaemic children to assess the stage of liver disease and selection of
      suitable cases for bone marrow transplantation (BMT).

PMID- 15461210
TI  - Prediction of stability factors at the domain interface of human gammaB
      crystallin maintaining the transparency of the eye lens.
AB  - OBJECTIVE: betagamma-crystallins are among the most long lived globular proteins
      known today. Interaction of the two domains through a hydrophobic interface is
      one of the major contributors to the stability of these crystallins. Changes in
      these interactions are either due to the amino acid substitutions or the changes
      in the orientations of the same amino acids leading to cataract formation. We
      have carded out a detailed analysis to observe the stabilizing effects of
      hydrophobic core residues at the domain interface of the predicted human gammaB
      crystallin structure. METHODS: Human gammaB-crystallin model was built by
      Homology Modeling hsing MODELLER4 based on the crystal structure coordinates of
      bovine gammaB-crystallin. In lens gammaB-crystallin, there are six non polar
      residues, three each in the two domains which form a hydrophobic core at the
      domain interface. We performed mutational studies at position 56 and analyzed the
      changes in the protein structure. Three mutants (Phe-->Trp. Phe-->Ala, Phe-->Asp)
      were constructed and analyzed for hydrogen bonding, ion pairs and accessibility
      by WHATIF web server. RESULTS: Being the largest amino acid among the six
      residues taking part in the hydrophobic interactions at the domain interface, Phe
      was predicted to be responsible for the greatest contribution to the stability at
      this region. Phe-->Ala mutant showed the largest structural changes in the
      vicinity of the mutated residue. CONCLUSION: The results obtained clearly
      emphasize the importance of hydrophobic interactions to the stability of
      crystallins. Mutations at the domain interphase could decrease the interactions
      between these domains thus causing destability.

PMID- 15461211
TI  - Treatment of acute fractures of the femoral shaft with reamed intramedullary
      interlocking AO nails.
AB  - OBJECTIVE: To review and audit our experience with closed intramedullary
      interlocking nailing for acute femoral shaft fractures. METHODS: All patients
      admitted to The Aga Khan University Hospital, over the last six years and with a
      minimum follow-up of twelve months, with acute fractures of the femoral shaft
      were included in the study. All patients treated for established non-unions and
      infections or with pathological fractures were excluded from the study. RESULTS:
      There were 89 fractures, 74% of whom were closed and 50% were associated with
      other orthopedic injuries. Most of these were younger patients involved in high
      velocity road traffic accidents. The union rate was 88% with 4.4% of fractures
      going into non-union. The remaining 8% of the fractures went into a phase of
      delayed union, but ultimately united, making the overall success rate to be
      95.6%. The mean time for union was 11.5 weeks. At the final clinical follow-up,
      4% of the patients had minor pain, 7% had limp, 4% had leg length discrepancy of
      more than 2 cm and 4% had decreased range of motion at the hip or knee joints. We
      had a 4% rate of superficial infection. There were 3 cases of pudendal nerve
      neuropraxia and 2 cases of deep vein thrombosis. CONCLUSION: Intramedullary
      Interlocking nailing is a safe and effective treatment modality for acute
      fractures of the femoral shaft. Proper surgical decision making regarding static
      versus dynamic mode of locking can avoid problems of delayed union.

PMID- 15461213
TI  - The grave problems being faced by our health sector.

PMID- 15461212
TI  - Frequency of hereditary thrombophilia: an AKUH experience.
AB  - OBJECTIVE: To determine the frequency of various causes of hereditary
      thrombophilia at a referral laboratory and the age and gender distribution.
      METHODS: This is a descriptive study incorporating a retrospective analysis of
      requests for thrombophilia screening sent to Clinical laboratory, Aga Khan
      University Hospital from November 1995 to May 2002. Patients were screened for
      hereditary causes of thrombophilia including Protein C, Protein S, antithrombin
      III, Factor V Leiden and homocysteine. Frequency of each disorder; and age and
      sex distribution was determined. RESULTS: All the patients suspected clinically
      for thrombophilia were screened. Of the 2825 patients, 70 were diagnosed to have
      inheritance as a cause of thrombophilia with a frequency of 2.3% for protein C
      deficiency, 1.4% for protein S deficiency, 1.5% for antithrombin III deficiency,
      14.2% for factor V leiden mutation and 2.0% for homocystenemia. CONCLUSION: All
      the causes of hereditary thrombophilia can be diagnosed by relatively simple
      laboratory methods, however because of the low frequency of these disorders the
      screening of general population is not indicated in the absence of clinical
      symptoms. More prospective studies are required to define the occurrence of these
      disorders and other causes of thrombosis.

PMID- 15461214
TI  - Permissive hypotensive resuscitation--an evolving concept in trauma.
AB  - Trauma fluid resuscitation continues to be a hotly debated issue. There is
      overwhelming experimental evidence to suggest that administration of
      resuscitation fluids is not entirely innocuous. Aggressive intravenous
      crystalloid administration in the presence of uncontrolled hemorrhage promotes
      continued bleeding and increases mortality. However this is countered by concerns
      that avoidance of fluids in the resuscitative phase may lead to tissue
      hypoperfusion, organ failure and death prior to control of bleeding. It may also
      have a deleterious effect on neurologic outcome in patients with TBI as well as
      increase the number of unnecessary operations. Currently there is no clear cut
      universal consensus pertaining to the optimal resuscitation strategy in trauma
      patients. However most prudent trauma surgeons propose, that a policy of
      judicious fluid administration to maintain the MAP in the 60-80 mmHg range is
      advisable and appropriate. Fluid resuscitation in trauma should be considered a
      double edged sword (too much too early or too little too late!). It should not be
      considered definitive therapy; as in a number of trauma patients it is only a
      temporizing measure, until surgical control of bleeding can be achieved.

PMID- 15461215
TI  - Incidental intrarenal-pelvic hydatid cyst discovered during percutaneous
      Nephrolithotomy (PCNL).

PMID- 15461216
TI  - Cutaneous manifestations of hyper-IgE syndrome in twins: a case report from Saudi
      Arabia.

PMID- 15461217
TI  - Clarithromycin induced digoxin toxicity: case report and review.

PMID- 15461218
TI  - Offspring sex ratio in smokers.
AB  - OBJECTIVE: To assess the ratio of male to female gender in the offspring of
      smokers and non-smokers. METHOD: The tool used for the survey was a
      questionnaire. Four hundred subjects were analyzed and were divided into three
      age groups. RESULTS: Out of 400 subjects 56.5% were smokers and 43.5% were
      nonsmokers. Overall offspring sex ratio in nonsmokers was 1.53 and 0.61 in
      smokers. CONCLUSION: The smoking might be a contributing factor to a lower male
      to female sex ratio of offspring along with Estrogenic pollutants which are
      everywhere in the environment contaminating food, drinking water and air.

PMID- 15461219
TI  - Why more than one in 10 people in Wales are waiting for treatment.

PMID- 15461220
TI  - Obesity ideas. The bottom line.

PMID- 15461222
TI  - Capital interest. Interview by Nick Edwards.

PMID- 15461223
TI  - Clinical management where medicine meets management. Driving force.
AB  - Hepatitis C is a potentially fatal virus, but as many as 90 per cent of people
      with it are unaware they are infected. A government campaign this autumn is
      likely to increase demand for testing. Much work on hepatitis C is done by drug
      teams in isolation, but work in the South West is leading to a more co-ordinated
      approach.

PMID- 15461224
TI  - Law. Can I get a witness?

PMID- 15461225
TI  - Finance. Panic postponed.

PMID- 15461226
TI  - London focus. Local produce.

PMID- 15461227
TI  - Information-clinical analysis. The data today. Real-time monitoring can alert
      trusts to clinical performance problems--before the star-ratings do it for them.
AB  - Collecting, analysing and distributing data on clinicians' performance has long
      been considered a touchy, even taboo, subject. However, a growing number of trust
      chief executives and medical directors are realising the value of creating an
      accurate picture of what they are doing and how well they are doing it--and in as
      close to real time as possible. As one put it: 'We can't afford to wait until the
      star-ratings are published to know if we are not doing well enough.' The spur for
      many has been the publication of standardised mortality ratio data for individual
      hospitals by health information providers Dr Foster. The poor performers wanted
      to pinpoint where their weaknesses were and the good performers wanted to know
      what they needed to do to maintain it. Over the past two years, the company has
      been working with acute trusts to introduce real-time monitoring and analysis of
      clinical information, which includes measurement of clinical outcomes, admission
      trends, mortality, length of stay, readmissions, base costs and infection rates.
      Some plan to show individual clinicians how their performance compares to
      colleagues and other departments, while others are being more cautious.
      Independently, HSJ spoke to a selection to find out how they were implementing
      the systems and what they hoped to achieve.

PMID- 15461229
TI  - International. The card from the continent. EU nations are adopting e-health--and
      the controversial e-health card--at varied rates, with Germany emerging as chief
      cheerleader.

PMID- 15461228
TI  - GP practices-patient information. It's not about the kit. When Trent SHA went
      looking for 'imagineers', it found great ideas in GP practices.

PMID- 15461230
TI  - Product design-user involvement. Mothers of invention. The diverse needs of
      patients are driving a radical programme of R&D innovation in Barnsley.

PMID- 15461231
TI  - Materials, timing, and techniques: immediate loading in extraction and grafted
      sites. Interview.

PMID- 15461232
TI  - Did President Reagan have mild cognitive impairment while in office? Living
      longer with Alzheimer's Disease.

PMID- 15461233
TI  - Lincoln sign, the 14th eponymous sign of aortic regurgitation.

PMID- 15461234
TI  - Dietary supplements in primary care. Botanicals can affect surgical outcomes and
      follow-up.
AB  - Dietary supplements are commonly used by patients of all ages, yet few patients
      reveal use of these products to their medical providers. Certain dietary
      supplements can react or interact with frequently used surgical medications-
      including anesthesia--and may cause serious unforeseen consequences or
      complications. Arrhythmias, poor wound healing, bleeding, photosensitivity
      reaction, and prolonged sedation are among the serious reactions during and after
      surgical and diagnostic procedures that have been attributed to these products.
      This article reviews the effects of the Few Gs (feverfew, ginkgo biloba, garlic,
      ginseng, and ginger), valerian, kava, St. John's wort, ephedra (Ma huang or
      metabolite), and echinacea. We recommend that all patients be advised to stop all
      dietary supplements at least 1 week prior to major surgical or diagnostic
      procedures; if a complication is noted, continued use of these products should be
      reviewed with patients.

PMID- 15461235
TI  - Crystal arthritis. Gout and pseudogout in the geriatric patient.
AB  - Gout and pseudogout are inflammatory arthritides due to monosodium urate and
      calcium pyrophosphate dihydrate crystal formation. Both are prevalent among
      geriatric patients, and can present as acute mono- or oligoarticular disease, or
      as a chronic polyarthropathy resembling osteoarthritis or rheumatoid arthritis.
      Gout in the geriatric patient is a disease affecting women, commonly associated
      with diuretic usage, often involves the fingers, may be complicated by the
      development of masses of uric acid crystals (tophi) in soft tissues, and is
      frequently polyarticular. Pseudogout in the geriatric patient has a variety of
      clinical presentations, may be acute or chronic, and should be considered in
      evaluating any patient with osteoarthritis occurring in an atypical distribution.
      Treatment includes the use of nonsteroidal anti-inflammatory drugs, colchicine,
      or corticosteroids. Gout may be impacted by dietary factors, weight reduction,
      and avoidance of certain forms of alcohol; uric acid-lowering agents are
      effective for refractory or chronic tophaceous disease.

PMID- 15461236
TI  - Grayish discoloration in symmetrical pattern on hands. Drug used for cardiac
      condition may produce skin problem.

PMID- 15461237
TI  - Alcohol abuse and dependence. A clinical update on alcoholism in the older
      population.

PMID- 15461238
TI  - Oral sulfonylureas and CV mortality.

PMID- 15461239
TI  - If not sulfonylureas, then what?

PMID- 15461240
TI  - The effect of calcium chloride in treating hyperkalemia due to acute digoxin
      toxicity in a porcine model.
AB  - BACKGROUND: The administration of intravenous (IV) calcium to treat hyperkalemia
      resulting from digoxin poisoning is considered potentially dangerous, based on a
      body of older literature which, in sum, reported increased cardiac glycoside
      toxicity with calcium administration (increased arrhythmias, higher rate of
      death). OBJECTIVE: This pilot study sought to determine if the administration of
      calcium chloride when compared to normal saline would affect time to death when
      given to hyperkalemic, digoxin toxic swine. METHODS: Digoxin IV at 0.25 mg/kg was
      determined to be appropriately toxic for this study. When arrhythmias consistent
      with hyperkalemia developed, animals were given either IV calcium chloride (CaCl)
      bolus (10 mg/kg, Group 1, n=6) or normal saline volume equivalent (Group 2, n=6).
      Three intervals were observed: Interval 1: time interval from digoxin
      administration (T0) to when ECG changes consistent with hyperkalemia developed
      (at which point calcium chloride or normal saline was administered); Interval 2:
      time interval from the development of ECG changes consistent with hyperkalemia to
      asystole; Interval 3: time interval from digoxin administration to asystole. Both
      groups were monitored for changes in heart rhythms, serum potassium levels, and
      time to asystole. RESULTS: The intravenous digoxin dose of 0.25 mg/kg induced
      hyperkalemia, arrhythmias, and death approximately 1 h after administration in
      all animals studied. Group 1: Interval 1 averaged 18.75 (S.D. +/-7.96) min,
      Interval 2 averaged 16.75 (S.D. +/-17.17) min, and Interval 3 averaged 35.5 (S.D.
      +/-14.49) min range; Group 2: average Interval 1 24.8 (S.D. +/-4.71) min,
      Interval 2 averaged 19.5 (S.D.+/-15.92), Interval 3 averaged 44.3 (S.D. +/-13.80)
      minutes. There was no statistically significant difference between the groups at
      any time interval, Interval 1 (p=0.43), Interval 2 (p=0.65), Interval 3 (p=0.40).
      There was no difference in serum potassium throughout the study period.
      CONCLUSION: The administration of intravenous CaCl in the setting of hyperkalemia
      from acute digoxin toxicity did not affect mortality or time to death at the dose
      administered.

PMID- 15461241
TI  - Survival pattern in patients with acute organophosphate poisoning receiving
      intensive care.
AB  - BACKGROUND: Approximately 35% of patients acutely poisoned with organophosphates
      (OP) in developing countries like Sri Lanka require intensive care and mechanical
      ventilation. However, death rates remain high. OBJECTIVE: To study the outcomes
      and predictors of mortality in patients with acute OP poisoning requiring
      intensive therapy at a regional center in Sri Lanka over a period of 40 months.
      METHODS: Retrospective analysis of all intensive care records of patients with
      acute OP poisoning admitted to the Intensive Care Unit (ICU) between March 1998
      and July 2001. RESULTS: During the study period, 126 subjects were admitted to
      the ICU with acute OP poisoning. Records of 10 patients were lost and those of 37
      were incomplete and hence were excluded. All the remaining 71 patients (59 male)
      had required endotracheal intubation and mechanical ventilation for a period of
      four (median) days (range 1-27) in addition to gastric lavage and standard
      therapy with atropine and oximes and adequate hydration. Of these 71 patients, 36
      (28 male) had died. Life table analysis demonstrated a steep decline in the
      cumulative survival to 67% during the first three days. Systolic blood pressure
      of < 100 mmHg and FiO2 of >40% to maintain a SpO2 of >92% within the first 24 h
      were recognized as poor prognostic indicators among mechanically ventilated
      patients. CONCLUSION: Mortality following OP poisoning remains high despite
      adequate respiratory support, intensive care, and specific therapy with atropine
      and oximes. One-third of the subjects needing mechanical ventilation and reaching
      intensive care units die within the first 72 h of poisoning. Systolic blood
      pressure of less than 100 mmHg and the necessity of a FiO2>40% to maintain
      adequate oxygenation are predictors of poor outcome in patients mechanically
      ventilated in the ICU.

PMID- 15461242
TI  - Ecgonine methyl ester protects against cocaine lethality in mice.
AB  - BACKGROUND: Plasma cholinesterase (PChE) metabolizes cocaine to ecgonine methyl
      ester (EME). Limited data demonstrate that EME is a mild vasodilator. Exogenous
      PChE protects against cocaine-induced seizures and lethality. It is unclear
      whether this protective effect results from enhanced degradation of cocaine, the
      loss of active metabolites (benzoylecgonine, norcocaine), or the production of a
      beneficial metabolite (EME). This study was designed to further investigate the
      pharmacologic effects of EME. METHODS: All experiments used female ICR Swiss
      albino mice weighing 20-30 grams. Mice were acclimated to 12 h alternating light
      dark cycles and given food and water ad libitum. Using a randomized, blinded
      protocol, 80 mice were then pretreated with either IP EME (50 mg/kg) in a 0.9%
      sodium chloride solution or an equal volume of 0.9% sodium chloride solution as
      control. Five minutes later, all animals received 126 mg/kg of cocaine IP and
      were observed for seizures and death. Fatality was compared using a Fisher's
      exact test, and the time to seizures and death were compared using a Mann-Whitney
      U statistic. RESULTS: Pretreatment with EME increased survival following cocaine
      (9/40 vs. 2/40, for EME vs. control, respectively, p<0.05). The median times to
      seizure and death for both groups were 2.0 vs. 1.5 min (p>0.05), and 4.5 vs. 4.6
      min (p>0.05) (EME vs. control for seizures and death, respectively). CONCLUSION:
      In this animal model, EME is protective against cocaine lethality. This effect is
      consistent with the previously described vasodilatory effects of EME. Further
      studies are indicated to determine whether the increase in EME produced by
      exogenous PChE administration contributes to the benefits that occur when PChE is
      given to cocaine-poisoned animals.

PMID- 15461243
TI  - Hexafluorine vs. standard decontamination to reduce systemic toxicity after
      dermal exposure to hydrofluoric acid.
AB  - INTRODUCTION: Dermal exposure to hydrofluoric acid (HF) may cause severe burns
      and systemic toxicity. Hexafluorine (Prevor, France) is a product marketed as an
      emergency decontamination fluid for HF skin and eye exposures. Documentation
      concerning Hexafluorine is scanty, and a recent study indicates that its ability
      to reduce HF burns is at most equal to that of water. OBJECTIVE: The present
      study was conducted to evaluate Hexafluorine's capacity to reduce HF-induced
      systemic toxicity. METHODS: Sprague Dawley rats were anesthetized, catheterized
      in the left femoral artery, and shaved on their back. A filter paper (3.5 x 6 cm)
      was soaked in 50% HF and applied on the back of each rat for 3 min. Thirty
      seconds after removal of the paper, a 3-min rinsing with either 500 mL
      Hexafluorine (group H), 500 mL water (group W), or 500 mL water followed by a
      single application of 2.5% calcium gluconate gel (group Ca) was carried out.
      Blood samples were analyzed for ionized calcium and potassium (before injury and
      1, 2, 3, and 4 h after) and also for ionized fluoride (1, 2, and 4 h after
      injury). RESULTS: The animals developed hypocalcemia, hyperkalemia, and
      hyperfluoridemia after the HF exposure. The only significant difference observed
      among the groups was in serum potassium at 1 h between group Ca and group W.
      However, there was a constant trend toward milder hypocalcemia and less
      pronounced hyperkalemia in group Ca compared to the other groups. There were no
      differences in the electrolyte disturbances between the Hexafluorine-treated
      animals and those treated with water only. Five of 39 animals died before
      completion of the experiment as a result of the HF exposure, one from group Ca
      and two from each of the other two groups. CONCLUSION: In this experimental
      study, decontamination with Hexafluorine was not more effective than water
      rinsing in reducing electrolyte disturbances caused by dermal exposure to
      hydrofluoric acid.

PMID- 15461244
TI  - Repeated episodes of endosulfan poisoning.
AB  - INTRODUCTION: A number of families in a rural area of Jabalpur District (Madhya
      Pradesh), India, were affected by repeated episodes of convulsive illness over a
      period of three weeks. The aim of this investigation was to determine the cause
      of the illness. METHODS: The investigation included a house-to-house survey,
      interviews of affected families, discussions with treating physicians, and
      examination of hospital records. Endosulfan poisoning was suspected as many
      villagers were using empty pesticide containers for food storage. To confirm
      this, our team collected blood and food samples, which were transported to the
      laboratory and analyzed with GC-ECD. RESULTS: Thirty-six persons of all age
      groups had illness of varying severity over a period of three weeks. In the first
      week, due to superstitions and lack of treatment, three children died. In the
      second week, symptomatic treatment of affected persons in a district hospital led
      to recovery but recurrence of convulsive episodes occurred after the return home.
      In the third week, 10 people were again hospitalized in a teaching hospital.
      Investigations carried out in this hospital ruled out infective etiology but no
      facilities were available for chemical analysis. All persons responded to
      symptomatic treatment. The blood and food samples analyzed by our team showed
      presence of endosulfan, which was confirmed by GCMS. One of the food items
      (Laddu) prepared from wheat flour was found to contain 676 ppm of alpha
      endosulfan. CONCLUSIONS: Contamination of wheat grains or flour with endosulfan
      and its consumption over a period of time was the most likely cause of repeated
      episodes of convulsions, but the exact reason for this contamination could not be
      determined. This report highlights the unsafe disposal of pesticide containers by
      illiterate farm workers, superstitions leading to delay in treatment, and
      susceptibility of children to endosulfan.

PMID- 15461245
TI  - Drug identification: a survey of poison control centers.
AB  - OBJECTIVE: The objective of this study was to determine current practices and
      opinions of poison center staff and directors regarding drug identification (ID)
      calls. METHODS: Surveys were developed and mailed to 911 poison center staff
      members and 69 managing directors at 69 poison control centers in the United
      States in December 2001. RESULTS: Responses were received from 317 staff members
      and 33 directors from 49 centers. Nearly half of the staff respondents stated
      that they had not received drug ID training beyond how to look up the identity of
      an oral medication. About one-half of staff and director respondents stated that
      their centers had only informal (unwritten) drug ID policies, while one-fourth
      each responded they had formal written policies or had no policy at all. A
      majority of respondents indicated that their centers either allow or require
      specialists to provide ID for non-ingestion-related cases. Nearly all staff and
      director respondents routinely provide ID services to law enforcement officers
      and health care professionals regardless of whether ingestion was involved.
      Slightly more than one-half of staff respondents inquire about possible ingestion
      with almost every request, while one-third only inquire when the caller gives
      some indication that ingestion may have occurred. Case-based questions reveal
      that different practices are utilized depending on the type of medication for
      which ID is being requested. Factors such as risk of liability, patient
      confidentiality, guardianship, and the person's best interest appear to
      contribute to decisions regarding the provision of medication ID. CONCLUSION:
      Drug identification practices vary from center to center throughout the United
      States. Though the service is greatly utilized, few centers have written
      policies. In addition, training for the provision of this service appears to be
      inadequate in many centers. The development of drug identification guidelines to
      be utilized throughout poison centers would provide much needed consistency and
      guidance.

PMID- 15461247
TI  - Space shuttle Columbia disaster: utilization of poison control centers in Texas
      and Louisiana.

PMID- 15461248
TI  - Future focus.

PMID- 15461246
TI  - A case of type F botulism in southern California.
AB  - BACKGROUND: Botulism caused by type F botulinum toxin accounts for less than 0.1%
      of all human botulism cases and is rarely reported in the literature. CASE
      REPORT: A 45-year-old woman presented to an emergency department complaining of
      blurred vision, difficulty focusing, and dysphagia. The treating physician
      initially considered the possibility of paralytic shellfish poisoning due to a
      report of shellfish ingestion, which was later determined to be frozen shrimp and
      a can of tuna, but no gastroenteritis or paresthesias were present. During the
      emergency department observation, the patient developed respiratory distress with
      hypercapnea and required intubation and mechanical ventilation. Within hours,
      ptosis, mydriasis, and weakness in the arms and legs developed. Bivalent (A, B)
      botulinum antitoxin was administered approximately 24 h from the onset of initial
      symptoms, but over the next two days complete paralysis progressed to the upper
      and lower extremities. Shortly thereafter a stool toxin assay demonstrated the
      presence of type F botulinum toxin. The patient subsequently received an
      experimental heptavalent botulinum antitoxin on hospital day 7 but paralysis was
      already complete. Her three-week hospital course was complicated by nosocomial
      pneumonia and a urinary tract infection, but she gradually improved and was
      discharged to a rehabilitation facility. Anaerobic cultures and toxin assays have
      yet to elucidate the source of exposure. CONCLUSION: We report a rare case of
      type F botulism believed to be foodborne in etiology. Administration of bivalent
      botulinum antitoxin did not halt progression of paralysis.

PMID- 15461249
TI  - Manpower.

PMID- 15461250
TI  - Public image.

PMID- 15461251
TI  - Ethical dilemma #48. "Who cares for the incompetent patient".

PMID- 15461252
TI  - Oral and maxillofacial pathology case of the month. Oral lymphoepithelial cyst.

PMID- 15461253
TI  - Health savings accounts (HSA) offer new option for health insurance.

PMID- 15461254
TI  - [Effects of pyrethroids on tyrosine hydroxylase in nigrostriatum of male rats].
AB  - OBJECTIVE: To study the effects of pyrethroids on tyrosine hydroxylase in
      nigrostriatum of male rats. METHODS: Different doses of permethrin and
      deltamethrin in corn oil were administered to rats by gavage for ten days, then
      PLC-Fluorescence detection was used to analyzed the contents of dopamine (DA),
      DOPAC and HVA in the Substantial Nigra and Striatum. The activities of TH were
      also detected by HPLC-Fluorescence detection. TH mRNA or TH protein levels were
      measured by RT-PCR and immunohistochemistry method. RESULTS: Contents of DA in
      Striatum in 1/10LD50 DM group have a significant change, the contents of DOPAC
      and the turnover rate of DA all increased (P < 0.05), but DA, DOPAC and (DOPAC +
      HVA)/DA did not have any significant change in Substantial Nigra. The activities
      and mRNA level of TH had obvious decrease in two DM groups, the TH protein levels
      also significantly decreased in 1/10LD50 DM group. CONCLUSION: Deltamethrin could
      decrease the activities, mRNA and protein levels in nigraostriatum of rats.

PMID- 15461255
TI  - [Role of telomerase in silica induced human cell transformation].
AB  - OBJECTIVE: To explore the role of telomerase in silica induced human cell
      transformation in vitro. METHODS: Human telomerase catalytic subunit (hTERT) was
      transferred into human embryonic lung fibroblasts (HELF). 160 microg/cm2 silica
      dusts were added to transform HELF and hTERT transduced HELF (HELF-T+)
      respectively. The telomerase activity and the length of telomere were determined.
      The growths of the normal and transformed cells were evaluated. RESULTS: The
      hTERT gene was steadily transferred into HELF. Silica dusts caused the
      transformations of both HELF-T+ and HELF. The telomerase activities in
      transformed cells were higher and the telomere length of transformed cells was
      longer than those of HELF. CONCLUSION: The changes of telomerase activity and
      telomere length may play an important role in the silica induced human cells
      transformation.

PMID- 15461256
TI  - [Activation of ERK1/2 and Elk1 in A549 cells induced by crocidolite].
AB  - OBJECTIVE: To investigate the role of extracellular signal-regulated kinase (ERK)
      1/2 and Elk1 in pulmonary disease induced by crocidolite asbestos fiber. METHOD:
      Western blotting and Immunoprecipitation were used to detect the expression of
      phosphorylated ERK1/2 and Elk1 in human bronchial airway A549 cell line
      stimulated by crocidolite. RESULTS: The expression of phosphorylated ERK1/2 and
      Elk1 were striking higher than those of the control, the differences were
      significant (P < 0.05). CONCLUSION: Phosphorylated ERK1/2 and Elk1 probably
      involved in the process of the diseases induced by crocidolite.

PMID- 15461257
TI  - [Effects on DNA damage and apoptosis and p53 protein expression induced by
      fluoride in human embryo hepatocytes].
AB  - OBJECTIVE: To study the effects of DNA damage and apoptosis and p53 expression,
      and to explore the relationship between apoptosis and p53 expression in human
      embryo hepatocytes induced by fluoride. METHODS: The rate of DNA damage,
      apoptosis and the level of p53 expression were investigated after the cells were
      incubated with sodium fluoride for about 24 hours. The concentrations of sodium
      fluoride of the control, A, B and C group were 0 microg/ml, 40 microg/ ml, 80
      microg/ml and 160 microg/ml individually. RESULTS: The rate of DNA damage of
      every group treated with sodium fluoride were significantly higher than the
      control group (P < 0.05). The percentage of apoptosis of B and C groups increased
      apparently (P < 0.05). The level of p53 expression of B and C groups were
      significantly higher than the control group (P < 0.01). CONCLUSION: Fluoride can
      increase the rate of DNA damage, and induce apoptosis and expression of p53 in
      human embryo hepatocytes. Furthermore, both apoptosis and the level of p53
      expression, there exists a rise tendency with the increase concentration of
      fluoride.

PMID- 15461258
TI  - [Effects of three environmental estrogens on expression of proliferation and
      apoptosis-associated genes in PEO4 cells].
AB  - OBJECTIVE: This study was designed to investigate the molecular mechanisms of
      proliferation and apoptosis by environmental estrogens (n-4-nonylphenol, NP;
      Bisphenol A, BisA; Dibutyl Phthalate, DBP) in ovarian cancer PEO4 cells. METHODS:
      PEO4 cells were maintained in DMEM medium with 10% neonatal bovine serum. Five
      days before the beginning of experiments, the cells were seeded in phenol red
      free DMEM medium containing 5% charcoal dextran-treated FBS. The cells were
      harvested and seeded in 6-well culture plates or in 75ml flacks. After various
      concentration of NP, BisA and DBP treatment for 72h, the cells were harvested and
      detected mRNA and protein expression of PCNA, bcl-2 and bax by reverse
      transcription-polymerase chain reaction and immunohistochemistry, respectively.
      RESULTS: 32 x 10(-7) mol/L NP and 32 x 10(-7) mol/L BisA could significantly up
      regulate PCNA and bcl-2 mRNA expression and down-regulate the bax mRNA
      expression, and 32 x 10(-6) mol/L DBP could up-regulate PCNA mRNA expression, but
      had no effect on bax and bcl-2 mRNA expression. These results were further
      confirmed by following immunohistochemistry. CONCLUSION: PCNA, bcl-2 and bax
      pathway might involve in cell proliferation and apoptosis events by environmental
      estrogens in ovarian cancer PEO4 cells.

PMID- 15461259
TI  - [Development of coated electrode of immobilized denitrifying bacteria and bio
      electrochemical denitrifying reactor].
AB  - OBJECTIVE: A coated electrode of immobilized denitrifying bacteria was developed
      to study the feasibility of electrochemical denitrification. METHODS: The coated
      electrode of denitrifying bacteria was made by batch cultivation and PVA
      immobilization using activated carbon fiber (ACF). The coated ACF electrode was
      used as cathode, while graphite as anode in bioelectrochemical reactor. RESULTS:
      After having been acclimated in two stages, mixotrophic and autotrophic
      denitrification stages, the denitrifying bacteria could use hydrogen as electron
      donor to reduce nitrate. When the initial nitrate concentration was 30.7mg NO3- 
      N/L, the denitrification rate was 38.4% at an applied electric current of 10mA
      and a hydraulic retention time of 12 hours. CONCLUSION: With great surface area
      and a rough surface, it was very easy to develop a biofilm on ACF. The membrane
      of PVA gel could adhere to the surface of ACF firmly. After having been
      acclimated, the denitrifying bacteria could use hydrogen generated by the
      electrolysis of water to be treated as electron donor to reduce nitrate.

PMID- 15461260
TI  - [Construction of the subtracted cDNA library in hypothalamus of the seasickness
      adaptive rats].
AB  - OBJECTIVE: To construct subtracted cDNA library in hypothalamus of the
      seasickness adaptive rats for providing theoretical basis for effective adaptive
      training against seasickness. METHODS: Suppression subtract hybridization
      technique was used, and forward and reverse hybridization was performed on the
      hypothalamus of seasickness adaptive rats and that of normal rats so that to
      construct subtracted cDNA library. Dot blot was used for differential screening
      the subtracted library. RESULTS: 23 fragments of differentially expressed genes
      was obtained including 10 up-regulating and 13 down-regulating fragments.
      CONCLUSION: Many played role in adaptability formation to seasickness such as
      SAM, vasopressin, and heme oxygenase.

PMID- 15461261
TI  - [Development and evaluation of a composite structural filter for removal of
      arsenic in drinking water].
AB  - OBJECTIVE: To develop a composite structural filter and evaluate its performance
      on-site for removal of high level arsenic in drinking water. METHODS: Composite
      filters were manufactured using iron loaded carbon powder and superfine PE resin
      as main components. Test water was prepared by spiking arsenic in raw drinking
      water. The filter application safety and removal effects on arsenic and other
      parameters were tested. RESULTS: The composite structural filter made of iron
      loaded carbon powder and superfine PE resin in equal quantity was safe for
      drinking water treatment and reached a capacity of 2.56mgAs/g for water with
      arsenic concentration of 0.4mg/L, and improved water turbidity and chemical
      oxygen demand apparently. CONCLUSION: The composite filter manufactured using
      iron loaded carbon powder and superfine PE resin as main components was
      appropriate for removal of arsenic in rural drinking water with high level of
      arsenic.

PMID- 15461262
TI  - [Study on the distributive regulation of Legionella pneumophila in different
      water].
AB  - OBJECTIVE: To grasp the distributive regulation and typing characters of
      Legionella pneumophila (Lp) in water. METHODS: Take water samples from the
      natural and living environment, Suspect strains were cultivated routinely from
      condensed water samples, then dual identification of serology identification and
      16S rRNA semi-nested PCR technology were used to identify typings of Legionella
      and Lp. RESULTS: 28 water samples were detected Legionella positive of the whole
      126 sampling sites (21 Lp positive among those). The legionella positive rates of
      sampling sites chosen in the natural and living environment were 32.1% and 22.2%
      respectively (Lp positive rates were 21.4% and 16.7% respectively); 36 samples
      were legionella positive of the 430 samples through a year (23 samples were Lp
      positive). The detection of positive rates were higher in summer and autumn, and
      also higher in air-conditioner cooling tower water, shower water and lake water
      in park. CONCLUSION: Lps are widely distributed over all kinds of water of the
      natural and living environment; the ambient temperature is an important factor
      for Lp's contamination, summer and autumn are the seasons with high incidence
      when Legionella contaminate and Legionellosis emit, and they also could be found
      in spring and winter. People contact closely with these water, such as park
      water, air-conditioner cooling tower water, shower water etc., which are high
      risks of legionella contamination and legionellosis transmission. Necessary
      measures should be taken promptly to protect public health.

PMID- 15461263
TI  - [Safety assessment and effect of new-type drinking water on immunity in mice].
AB  - OBJECTIVE: To assess the safety of four kinds new-type drinking water and explore
      its effect on immunologic function in mice. METHODS: Its acute oral toxicity and
      Genotoxicity were detected using acute toxicity test, Ames test, micronucleus
      assay of mice bone marrow cell and mice sperm malformation test. Its effects on
      cellular, humoral immune function were assessed respectively by metatarsus
      thickening method, Jerne-improved slide method. RESULTS: Its acute oral LD50 in
      mice were greater than 10000mg/kg BW, three genetic toxicity tests showed
      negative results, the metatarsal injected with SRBC and number of antibody
      forming cells were no evidently thicker in test group than in control group.
      CONCLUSION: The result did not indicate the genotoxicity of the four kinds new
      type drinking water and they couldn't effect immunologic function in mice.

PMID- 15461264
TI  - [Impact of extra waters on immunosystem in mice].
AB  - OBJECTIVE: To study impact of extra waters on immunosystem in mice-alkaline
      ionized water, mineral-ecology water, activated water, and pure water. METHODS:
      According to Function Assessment and Experiment for Function Food, 1996, the
      ratio of spain and body weight, the ratio of thymus and body weight, the delayed
      type hypersensitivity (DTH), the phagocytosing functions by cock RBC, the plaque
      forming cell (PFC) and HC50 testing were assessment with 120 male Balb/c mice of
      17.8 - 23.3 g (group I), the mice were divided into four group, and drank daily
      the four kinds of waters respectively until 50 days. The lymph cell
      transformation by ConA and NK cell activity were assessment with other l20 male
      Balb/c mice of 17.8 - 23.3 g (group II), the mice were divided into four group
      and drank daily the four kinds of waters respectively until 50 days. The
      phagocytosing functions by carbon powder were assessment with other 120 female
      Balb/c mice of 16.7 - 22.0 g (group III) were divided into four group and drank
      daily the four kinds of waters respectively until 50 days. The data were
      statisticed by Stata soft. RESULTS: Other three waters compared with the pure
      water: (1) Alkaline ionized water and activated water can alleviate the body
      weight increase of male Balb/c mouse (P < 0.01 & P < 0.05), but alkaline ionized
      water, mineral-ecology water, activated water don't impact on the female Balb/c
      mouse body weight (P > 0.05). (2) Activated water can remarkably increase the
      ratio of thymus and body weight (P < 0.05), and increase the phagocytosing
      ability by cock RBC (P < 0.01), and increase the NK cell activity (P < 0.01). (3)
      The three extra waters don't impact on other items for the Balh/c mouce.
      CONCLUSION: The study must be continued to impact on immunosystem in mice for
      extra waters.

PMID- 15461265
TI  - [Tenax TA adsorption/thermal desorption/capillary gas chromatography for
      monitoring BTX in the ambient air].
AB  - OBJECTIVE: A method for monitoring low concentration of benzene, toluene, p
      xylene, o-xylene (BTX) in ambient air is set up. The optimum of desorption and
      analysis parameter is selected. METHODS: Tenax TA adsorption/thermal
      desorption/capillary gas chromatography is used. RESULTS: The relative standard
      deviation of benzene, toluene, p-xylene, o-xylene in ambient air are from 4.30%
      to 10.81%, which shows this method has good repeatability. The recoveries of BTX
      are more than 94%. The minimum detectable concentration to benzene, toluene, p
      xylene, o-xylene is 0.09, 0.12, 0.23, 0.26 microg/m3 respectively. CONCLUSION:
      This method can be used to determinate low concentration of BTX in ambient air.

PMID- 15461266
TI  - [Effect of 900MHz electromagnetic fields on energy metabolism of cerebral
      cortical neurons in postnatal rat].
AB  - OBJECTIVE: To investigate the effects of low intensity microwave (900MHz)
      electromagnetic fields (EMF) on energy metabolism of cerebral cortical neurons in
      postnatal rat. METHODS: Neurons were exposed to low intensity 900MHz continuous
      microwave EMF (9mW/cm2, SAR = 3.22mW/g) for 2 hours per day in 4 or 5 consecutive
      days and for 12 hours at a time. The authors chose cytochrome oxidase (CCO) as
      the biological end. RESULTS: The results of cytochemistry showed that compared to
      the sham-exposed, a significant decrease of cytochrome oxidase activity in
      neurons exposed for 2 hours per day and the neurons exposed for 12 hours to be
      immediately experimented (P < 0.001). CONCLUSION: Down-regulation of CCO should
      be classified as 'non-thermal effects'. Cumulated power effect were observed in
      neuronal response to the microwave. The influence on the CCO of the chosen
      microwave EMF could be recovered to some extent. The effects had no close
      relation between the first exposure and the cultured age of neurons.

PMID- 15461267
TI  - [Inhibition of grape procyanidin on the expression of SSTR-2 mRNA in the hepatic
      cells induced by N-nitroso compounds].
AB  - OBJECTIVE: To study the effect of grape procyanidin (GPC) on the expression of
      somatostatin receptor 2 mRNA induced by N-nitroso compounds in the hepatic cells
      of rats. METHODS: NaNO2 was fed to Wistar rats to induce hepatocytes' mutation,
      and GPC was given in dose of 100mg/kg and 10mg/kg respectively through mouths to
      the rats of the two experimental groups at the same time. After eight weeks, situ
      hybridization was applied to measure the expression level of SSTR-2 mRNA in rats'
      hepatic cells. RESULTS: The positive cells rate of SSTR-2 mRNA expressed in the
      injury comparison group and the high-dose GPC group were 19.89% and 7.83%
      respectively and the difference between the two groups had statistical
      significance (P < 0.05). CONCLUSION: GPC had inhibitory effect on N-nitroso
      compounds-induced abnormal expression of SSTR-2 mRNA in hepatic cells of rats.

PMID- 15461268
TI  - [Stability of protein to digestion in vitro].
AB  - OBJECTIVE: To establish test model of stability of different protein to digestion
      in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). METHODS:
      The component of SGF and SIF being from the United States Pharmacopeia, the
      stability of various proteins were tested. The concentration of protein in
      SGF/SIF was 0.5mg/ml. At intervals of 0s, 15s, 30s, 60s, 2min, 4min, 8min, 15min,
      30min and 60min, the samples were taken out. According to the results of SDS
      PAGE, the stability of various proteins to digestion in SGF/SIF was observed.
      RESULTS: The experiment showed that trypsin inhibitor from soybean, beta
      lactoglobulin A from bovine milk and beta-lactoglobulin B from bovine milk were
      stable within 60min in SGF. Peanut lectin was digested within 8min. Most soybean
      lectin was digested within 8min, but the degraded fragments still existed.
      Ovalbumin, ovomucoid, BSA, soybean lipoxygenase and potato acid phosphatase were
      digested within 15s. The results in SGF were not consistent with the results in
      SIF. Trypsin inhibitor from soybean, beta lactoglobulin A from bovine milk, beta
      lactoglobulin B from bovine milk, BSA, ovalbumin, ovomucoid, soybean lectin and
      peanut lectin were stable for 60min in SIF. The degraded fragments of soybean
      lipoxygenase and potato acid phospatase exited within 60min. CONCLUSION:
      Different proteins showed different stability to SGF/SIF. According to the
      difference, model of evaluating the stability of protein to SGF/SIF was
      established.

PMID- 15461269
TI  - [Preparation and application of monoclonal antibodies against cowpea trypsin
      inhibitor].
AB  - OBJECTIVE: To detect cowpea trypsin inhibitor (CpTI) in transgenic rice leaves
      and build a possible method to assay transgenic plant with CpTI. METHODS:
      Nowadays gene assay is the most useful method to detect transgenic plants. But
      false positive may be got in gene assay and effective protein may not be
      produced. So assay of foreign protein is the most direct and conformable method.
      Monoclonal antibodies were got through traditional method of preparation.
      RESULTS: Three monoclonal antibodies were got. Detection of CpTI in transgenic
      rice leaves with these three antibodies mixes through Western blotting was
      conducted and the result was satisfying. CONCLUSION: The method of using the
      mixes of three antibodies to detect the CpTI in plants through Western blotting
      was satisfying.

PMID- 15461270
TI  - [Effect of chronic alcohol administration on pancreatic islets and oxidative
      stress of rats].
AB  - OBJECTIVE: To study the role of reactive oxygen species (ROS) and nitric oxide
      (NO) in the effect of chronic alcohol administration on pancreatic islets.
      METHODS: A oral administration of alcohol (6ml/kgBW) in different concentration
      (10%, 30% and 50%) was given to rats for 90 days. RESULTS: The fasting serum
      glucose was markedly increased while fasting serum insulin was markedly reduced
      in high dose alcohol group in comparison with that in control group. Compared
      with control rats, we observed the significant decrease of the ratio of insulin
      immune active product area to pancreas area as well as that to islets area in
      high dose alcohol group. Compared with control rats, there were significant
      increase of ROS level, NO content and malondialdehyde (MDA) content, and
      significant decrease of total superoxide dismutase (T-SOD) activity in serum and
      pancreas homogenate in high dose alcohol group. Our observations indicate that
      ROS and NO play an important role in the effect of chronic alcohol administration
      on pancreatic islets of rats. CONCLUSION: Free radicals in pancreas induced by
      chronic administration of high dose alcohol caused oxidative injuries of
      pancreatic islets.

PMID- 15461271
TI  - [Study on the relationship between the polymorphism of P22phox C242T, vitamin E
      and coronary heart disease].
AB  - OBJECTIVE: To study the C242T mutation frequency of the cytochrome b4 (P22phox)
      in Chinese and to further ascertain the relationship between the polymorphism of
      P22Phphox C242T, vitamin E and coronary heart disease (CHD). METHODS: 151
      patients with CHD and 254 controls were genotyped for the P22phox C242T
      polymorphism by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) analysis, the concentrations of the vitamin E in plasma
      were measured by reversed-phase high performance liquid chromatography (RP-HPLC).
      RESULTS: The study shows that the allele frequency of C and T is 92.72% and 7.28%
      in the whole people and the polymorphism of P22phox C242T is associated with CHD
      in Chinese. Vitamin E is protective against CHD and there is effect on the
      progress of CHD in the interaction of the polymorphism of P22phox C242T and
      vitamin E. By stepwise Logistic regression analysis the results suggest that
      male, smoking, non-drinking, hypertension, diabetes, stroke of parents and low
      concentration of vitamin E in plasma are the possible risk factors in CHD.
      CONCLUSION: The polymorphism of P22phox C242T is associated with CHD in Chinese.
      Vitamin E is protective against CHD and there is effect on the progress of CHD in
      the interaction of the polymorphism of P22phox C242T and vitamin E.

PMID- 15461272
TI  - [Effect of dietary mineral nutrients and vitamins on metabolism of rat fed with
      high fat].
AB  - OBJECTIVE: To explore dietary mineral nutrients (calcium, magnesium, zinc,
      ferric, chromium) and vitamins (vitamin A, B1, B2, C, D, E) on the effect of
      metabolic disorder of Wistar rat fed with high fat diet. METHODS: Fifty obesity
      prone male rats were randomly divided into 5 groups: A group were fed with basic
      diet, B group were fed with high fat diet and normal minerals and vitamins, C
      group were fed with high fat diet with lower minerals and vitamins, D group were
      fed with high fat diet with higher minerals and vitamins, E group were fed with
      high fat diet with only higher calcium. After 8 weeks, blood glucose, serum
      insulin and leptin, serum triglycerides, cholesterol and high-density lipoprotein
      were measured respectively. RESULTS: The body weight and fat content in B group
      were significantly higher than those of other groups. The body weight in D, E
      group decreased significantly compared with B group, both of which are similar
      with A group. In the case of blood glucose, serum insulin, leptin,triglycerides,
      cholesterol and high-density lipoprotein, they all have the tendency of
      decreasing in D group compared with E group. CONCLUSION: In addition to reducing
      body weight and fat content, dietary mineral nutrients and vitamins can also
      ameliorate the blood glucose and improve hyperinsulinemia and hyperleptinemia,
      modify the metabolic disordor of rat fed with high fat diet.

PMID- 15461273
TI  - [Effect of different dosage of vitamin A supplement on anti-oxidative activity
      and the fluidity of erythrocyte membrane in rats].
AB  - OBJECTIVE: To investigating the effect of vitamin A (VA)at different dosage of
      vitamin A on anti-oxidative activity and the fluidity of erythrocyte membrane in
      rats and safe dosage. METHODS: Wistar rats selected for VA supplement trial were
      randomly divided into four groups. The first group was no VA supplement as a
      control, and the second, third, forth groups were daily supplemented with VA
      11.43, 42.86 and 142.86 microg RE/kg respectively. The trial lasted 8 weeks.
      Vitamin A was dissolved in soybean oil and daily given to animals by gavage. The
      blood samples were collected at the end of the trial. The level of plasma VA was
      analyzed by fluorescent spectrometry. SOD, GSH and MDA in plasma were analyzed.
      The blood erythrocyte membrane fluidity was detected by fluorescence polarization
      method. RESULTS: The results showed that plasma retinol levels increased with
      increase of vitamin A. After 8 week supplement, SOD activities in the second and
      the third groups were lower than those of the first and the fourth group (P <
      0.01), which was the highest in the four groups (P < 0.01). The level of plasma
      MDA in the third was the lowest (P 0.01). GSH-Px activity was higher in the third
      group than other three groups (P < 0.01). Moreover, P (fluorescence polarization)
      was lower in 42.86 microg RE/kg group than other three groups, and P
      significantly increased in the fourth group (P < 0.01), which indicates that the
      erythrocyte membrane fluidity increased significantly after 42.86 microg RE/kg
      vitamin A supplement. CONCLUSION: The supplement of 42.86 microg RE/kg VA could
      improve anti-oxidative activity and enhance erythrocyte membrane fluidity.
      Overtake vitamin A could produce a poisoning effect and a stronger oxidative
      damage.

PMID- 15461274
TI  - [Effect of Ginkgo biloba L leaves on oxidation of human low density lipoproteins
      in vitro].
AB  - OBJECTIVE: To study the effects of Ginkgo biloba L leave on oxidation of human
      low density lipoproteins (LDL) induced by Fe2+ or Cu2+ in vitro. METHODS: LDL was
      oxidized by Fe2+ or Cu2+ for 1, 2, 4, 6h, while it was protected by extracts from
      leaves of Ginkgo biloba L. ( EGB761), ginkgo flavonids(GF) and ginkgo
      terpenlactones (GT). Lipofusion (LF), malondialdehyde (MDA) and vitamin E (VitE)
      were measured as the index of the oxidation of LDL by means of Fluorescence
      spectroscopy methods. RESULTS: Each extract can inhibit the oxidation of LDL, the
      inhibition of each extract is increasing during the first 4 hours and
      subsequently decrease, after 6 hours all the inhibitor have almost lost their
      ability on antioxidation. CONCLUSION: EGB761, GF and GT are effective antioxidant
      and the anti-oxidation vary with time.

PMID- 15461275
TI  - [Experimental studies of lycopene in inhibiting tumor growth in S180-bearing
      mice].
AB  - OBJECTIVE: To observe the effect of lycopene (LP) on tumor in mice. METHODS: S180
      bearing mice were used as animal model. The mice were given LP by oral. The
      effects of LP on tumor weight, immune function and antioxidative enzyme were
      measured respectively. RESULTS: LP group could promote spleen lymphocyte
      proliferation, NK activity and increase activity of SOD, GSH-Px and decreased the
      concentrations of MDA significantly compared with model group (P < 0.05).
      CONCLUSION: LP could inhibit the growth of S180 tumor. The antitumor effect may
      be related to its immune function and antioxidative effect.

PMID- 15461276
TI  - [Correlation comparison of uterotrophic assay and E-SCREEN assay for estrogenic
      activities].
AB  - OBJECTIVE: To evaluate the correlation of uterotrophic assay in immature mice and
      E-SCREEN assay for estrogenic activities using 17beta-estradiol (17beta-E2) and
      four botanical extracts (Fructus Foeniculi, Fructus Psoraleae, Radix Cyathulae
      and Radix Sophorae Tonkinensis). METHODS: Weanling female Kunming mice weighed 10
      - 12 g were given botanical extracts (10 g/kg BW, i.g) and 17beta-E2 (0.5 mg/kg
      BW, s.c), respectively, for 9 days. Uterine and ovary weights of mice were
      measured after killed. Human breast cancer MCF-7 cells were cultured and treated
      with botanical extracts (final concentration: 10 mg/L) and 17beta-E2 (final
      concentration: 0.3 micromol/L) for 120 h, respectively. The doubling time of cell
      growth was calculated and analyzed its correlation with average uterine weights
      obtained from uterotrophic assay. Results Four botanical extracts, as well as
      17beta-E2, increased uterine weights of mice significantly (P < 0.05 or P < 0.01)
      and shortened the doubling time of cell growth. And uterine weights were
      inversely correlated with the doubling time of cell growth (r = -0.967, P <
      0.01). CONCLUSION: The result of uterotrophic assay in immature mice was
      consistent with that of E-SCREEN assay when evaluating estrogenic activities.

PMID- 15461277
TI  - [Effect of iron and zinc levels in diet on development of bone in growing rats
      exposed to lead].
AB  - OBJECTIVE: The purpose of this paper was to explore the effect of iron and zinc
      in diet on development of bone in growing rats exposed to lead and observed the
      change of bone mineral content (BMC) and bone mineral density (BMD). METHODS: The
      growing rats were fed with diet added with different levels of iron, zinc and
      lead for 12 weeks. RESULTS: Long-term exposure to lead may inhibit the
      development of bone and reduce BMC and BMD, it can be improved the weight and
      length of bone and increased BMC and BMD following the increased in iron and zinc
      levels in the diets, but the lead level of bone increases. CONCLUSION:
      Supplementary suitable iron or/and zinc could improve the BMC and BMD, the
      mechanism of iron and zinc in diets on bone exposed to lead should be further
      research.

PMID- 15461278
TI  - [Effects of genistein on bone mineral density and biomechanical properties and
      morphometric parameters in ovariectomized rats].
AB  - OBJECTIVE: To investigate the effects of genistein on bone mineral density and
      biomechanical properties and morphometric parameters in ovariectomized rats.
      METHODS: Forty-seven Wistar rats were randomly allocated into six groups: sham
      operated (sham), ovarietomized (ovx), ovarietomized supplied with diethyl
      stilbestrol (E, 20 microg/kg BW) or genistetin (25, 50, 100 mg/kg BW). After the
      rats had been fed for three months, the bone mineral density and biomechanical
      properties and histomorphometric parameters of the rats was analysed. RESULTS:
      The trabecular bone volume and the mean trabecular plate density and bone density
      of ovariectomized rats were significantly decreased, while the mean trabecular
      plate space increased compared with sham animals. After three months
      supplementation to ovariectomized rats, trabecular bone volume and mean
      trabecular plate density increased. CONCLUSION: Genistein can reduced bone loss
      on ovariecromized rats.

PMID- 15461279
TI  - [Effects of genistein on NOS, GSH-Px activities and NO, GSH, MDA contents in MCF
      human breast cancer cells].
AB  - OBJECTIVE: To investigate the mechanism that the genistein inhibit the MCF human
      breast cancer cell. METHODS: The activities of glutathione peroxidase (GSH-Px),
      nitric oxide synthetase (NOS) and the contents of nitric oxide (NO), glutathione
      (GSH), malondialdehyde (MDA) both in culture supernatant and cells were examined
      by enzyme method and spectrophotometry respectively. RESULTS: With genistein
      increasing, the activities of GSH-Px, NOS and the contents of NO increased
      significantly (P < 0.05), while the contents of GSH, MDA decreased both in
      culture supernatant and cells (P < 0.05). CONCLUSION: Genistein can affect NO
      synthesis and antioxidation in MCF breast cancer cells. It may be one of the
      mechanisms that the genistein inhibit the MCF breast cancer cells growth.

PMID- 15461280
TI  - [Digestive and absorptive characteristic of starches determined in vitro and in
      vivo].
AB  - OBJECTIVE: To compare the different digestive and absorptive characteristic of
      digestible starch (DS) and resistant starch (RS), using both in vitro and in
      vitro methods. METHODS: Firstly, DS and RS content in four starchy samples were
      determined in vitro according to Englyst's method. Secondly, DS and RS digestion
      and absorption were evaluated by determination of four-hour blood glucose level,
      after direct injection of DS and RS solution into rats' duodenum. And in another
      animal test, the effect of RS on apparatus absorption rate of carbohydrate and
      nitrogen and secretion of gastric acid and pepsin was observed. RESULTS: In
      vitro, it was showed that general cornstarch was rich of DS, while 76% of potato
      starch was RS. In vitro, it was tested that after injection of DS into duodenum,
      most of DS could be absorbed in 120 min with high peak value of plasma glucose.
      While, RS needed more time to complete its absorption, and its apparatus
      absorption was up to 96%. It was also showed that RS could increase fecal
      nitrogen excretion, decrease nitrogen apparatus absorption rate and change
      gastric acid and pepsin excretion. CONCLUSION: By both in vitro and in vitro
      methods, RS is identified to be absorbed slowly but completely. The results
      partly support Englyst's method, which regards 120min as the time point to
      separate DS with RS in vitro.

PMID- 15461281
TI  - [Survey on the cadmium levels in fish, crustaceans and bivalve mollusks in China
      of 2002].
AB  - A survey on the cadmium content of fresh water, marine fish bivalve mollusks and
      crustaceans in China was carried out by the National Institute of Nutrition and
      Food Safety, Chinese Center for Disease Control and Prevention in 2002. The fish
      from fresh water (n = 193), marine (n = 367), crustaceans (n = 318) and bivalve
      mollusks (n = 512) were collected from 14 provinces and cities and analyzed by
      AAS. It was found that the samples with mean concentration between 0.06-0.53
      mg/kg. However, some of samples were up to 8 mg/kg, indicating that the cadmium
      content of some fishes exceeded the maximum level of national standards.

PMID- 15461282
TI  - [Contamination source identification study of organochlorines pesticides in 2000
      Chinese total diet study].
AB  - The third Chinese total diet study to estimate dietary intake of contaminants was
      carried out in 2000. The levels of HCH and DDT residues were less significant in
      most of foodstuffs, but the level of HCH residues of aquatic foods in South 2 and
      in North 1 is respectively 75.99microg/kg and 170.72microg/kg, and the ratio of
      gamma-HCH is 90% of the total HCHs residues. To identify the contamination source
      of gamma-HCH, the individual province composite samples and the individual
      samples of aquatic foods from individual province were further analyzed. The
      level of gamma-HCH in bream (Megalobrama amblycephala) sample in Hubei province
      is 546.4microg/kg, which is 98.3% of all HCHs (exceeding the 0.1mg/kg HCHs EMRL
      in fish), the level of gamma-HCH in carp (Cyprinus carpio Linnaeus) sample in
      Heilongjiang province is 602.4microg/kg, which is 98.5% of all HCHs. The two
      samples polluted by Lindane were confirmed by GC-MS. The result suggests that
      Lindane has been used irregularly in some areas in China.

PMID- 15461283
TI  - [Analysis on main factors for successful quitting--study on the one-year follow
      up for Chinese 'Quit and Win' in 2002].
AB  - OBJECTIVE: China took part in the fifth 'Quit & Win in 2002 which was held by WHO
      and KTL in Finland. 27398 participants from eleven cities in China took part in
      the contest. Then we had a one-year follow-up research from May to June in 2003.
      METHODS: A random sample of 1298 was surveyed by mailing, telephone and visiting.
      RESULTS: One year were 27.71%. Main factors for successful quitting in one year
      included "intention to stop smoking completely by participating the contest",
      "age", "marriage", et al. But some factors had no effect on the successful
      quitting, such as cessation measures, helping from others, et al. CONCLUSION: It
      is important for smokers to make a decision and perseverance to stop smoking.

PMID- 15461284
TI  - [Status of perfluorochemicals in adult serum and umbilical blood in Shenyang].
AB  - OBJECTIVE: To study the status of perfluorooctane sulfonate (PFOS), and
      Perfluorooctanoic acid (FOA) pollution in serum and umbilical blood among general
      people in Shenyang area. METHODS: Concentration of PFOS and PFOA in adult serum
      and umbilical blood samples was measured by means of liquid phase
      chromatography/mass spectrograph selective iron monitoring (PFOS: m/z = 499,
      PFOA: m/z = 413). RESULTS: It was showed that geometric mean of serum
      concentration of PFOS of male was 40.73microg/L and that of female was
      45.46microg/L, PFOA is 11.53microg/L and 8.97microg/L. Geometric mean
      concentration of PFOS and PFOA in umbilical blood was 2.214microg/L and
      0.264microg/L. There was no correlativity between concentration of PFOS, PFOA and
      age in adult serum and umbilical blood. CONCLUSION: It was suggested that there
      was PFOS contamination in common group in Shenyang. Also, fetus was exposed in
      PFOS and PFOA during its embryonic period. There were also PFOS and PFOA
      pollution in human umbilical blood samples.

PMID- 15461285
TI  - [A case-control study of risk factors of low birth weight at term].
AB  - OBJECTIVE: To analyze the risk factors of low birth weight, the authors conducted
      a matched case-control study. METHODS: 155 women which infants were singleton
      term SGA cases and 155 with singleton term non-SGA controls were interviewed.
      Cases and controls were matched by infant sex and maternal age. Analyses were
      performed by conditional logistic regression. RESULTS: Low prepregnancy weight (<
      or = 52kg), low weight gain (< or = 16kg), passive smoking and drinking tea
      during pregnancy, dying hair, marcel or curium oil three month before pregnancy
      and during pregnancy, low husband height (< 173cm), and maternal BMI (> or = 19)
      were associated with risk of term SGA. The odds ratio of those risk factors were
      2.08, 2.83, 3.07, 2.94, 3.42, 2.72, 5.67, 2.92 and 0.41 respectively. CONCLUSION:
      It was also found significant positive interactions between low maternal weight
      and low weight gain, and dying hair, marcel or curium oil three month before
      pregnancy and during pregnancy, and low husband's height, and passive smoking
      during pregnancy.

PMID- 15461286
TI  - [Feasibility of telephone screening interview in a validity and reliability study
      of telephone interview to assess dietary intake in Beijing, Shanghai and Hong
      Kong].
AB  - OBJECTIVE: To understand the feasibility of telephone interviews to achieve
      recruitment of subjects to assess the validity and reliability of the telephone
      interview in eliciting dietary intake. METHODS: A multi-phase study was conducted
      in Beijing, Shanghai and Hong Kong in 2002. RESULTS: Three hundred eligible women
      aged from 20 to 49 years old were recruited in those cities. In the screening
      interview, 2462 random telephone numbers were dialed with 95% of dials completed
      within 5 times of attempts. The average number of dial for the completion was two
      calls, the rates of completion and refusal conversion were not improved
      remarkably by the increase of calls although some calling attempts reached 20
      times. Regarding the processing of the sampling pools in those three cities,
      Beijing had a lower efficiency rate but a satisfactory completion rate, Shanghai
      was good in both indicators, and Hong Kong had a good efficiency rate but lower
      completion rate. The overall telephone screening interview completion rate was
      42%, with Hong Kong having the lowest rate (32%) compared with Beijing and
      Shanghai (47% and 50%, respectively, P < 0.001). CONCLUSION: The telephone
      interview method could successfully reach the target of urban Chinese women and
      earn their cooperation with a satisfactory completion rate.

PMID- 15461287
TI  - [Study on analysis of thioglycolic acid in cosmetics by ion chromatography].
AB  - OBJECTIVE: An analytical method of determinating thioglycolic acid in cosmetics
      by ion-exchange chromatography suppressed conductivity detection has been
      developed. METHODS: A high capacity anion exchange column, IonPacAS11-HC column
      was used. 25mmol/L NaOH + 1% methanol was used as eluent, and the flow rate was
      set up at 0.85ml/min. Samples were pretreated by extraction with CHCl3 to remove
      some organic substance, and then upper clean liquid was injected. RESULTS: The
      influence of samples' pH, coexist anion and the concentration of methanol in
      eluent on determination was discussed. The method enjoyed a wide linear range and
      good precision. The detection limit was 2.3mg/kg. The average recoveries were
      91.5% - 10.0%, and the relative standard deviation (RSD%) was less 0.941.
      CONCLUSION: The results showed that the method was simple, accurate and might be
      good for application.

PMID- 15461288
TI  - [Comparison between effects of mechanical mince on the DNA damages of spleen,
      liver and kidney cells in mice].
AB  - OBJECTIVE: To study whether there are differences between effects of the DNA
      damages of the spleen, liver and kidney cells in mice caused by mechanical mince
      and the spleen, liver and kidney in mice can be dissociated into single cells by
      mechanical mince or not. METHODS: No drug was administrated to the tested group
      mice, and Cyclophosphamide was administrated to the control group mice with 150
      mg/kg doses. Then the three kinds of single cell suspensions were prepared by
      mechanical mince. The cell livabilities were detected by trypanblau coloration,
      and effects of mechanical mice on the DNA damages of the three kinds of cells
      were detected by single cell gel electrophoresis. RESULTS: The single cell
      quantity prepared from spleen, liver and kidney in short time by mechanical mince
      can meet completely the needs of comet assay. The percentages of cells with
      comets of the tested group were respectively 3.20%, 6.21%, 9.22% and the DNA
      migrations were respectively 27.30microm, 28.45microm, 47.10microm. There were
      significant differences between the percentages of cells with comets in the
      tested groups (P < 0.05). In the DNA migration test, there were significant
      differences between the spleen cells and kidney cells or between liver cells and
      kidney cells of the three tested groups (P < 0.05). The percentages of cells with
      comets and the DNA migrations of the three types cells in tested groups were low
      significantly (P < 0.01, P < 0.001) compared with the corresponding positive
      control groups. CONCLUSION: The effects of mechanical mince on the DNA damages of
      spleen, liver and kidney cells became stronger and stronger orderly. Spleen and
      liver can be dissociated into single cells by mechanical mince more
      appropriately.

PMID- 15461289
TI  - [Identification of types of yeast polluting the foodstuff sold in Beijing].
AB  - OBJECTIVE: To investigate and to specify types of yeasts polluting the foodstuff
      sold in Beijing market. METHODS: The yeasts strains isolated from the samples
      delivered was identified by API 20C AUX. Combining the results obtained from API
      20C AUX tests and morphological observation of yeasts. RESULTS: There were 29
      strains, and 15 species. In the 29 strains, the Pichia membranaefaciens was the
      mostly prevalent, accounting for 20.69% followed by Zygosaccharomyces bailii
      (17.24%) and Candida krusei (10.34%). Totally, there were spoilage yeasts of 7
      species 19 strains, accounting for a percentage of 65.52. Foodstuff made of bean
      and sauce were the mostly polluted by yeasts. CONCLUSION: Relevant supervision
      and inspection work should be strengthened.

PMID- 15461291
TI  - [Methods of hygromycin B phosphotransferase activity assay in transgenic plant].
AB  - Hygromycin B phosphotransferase (HPT) is a widely used selectable marker protein
      of transgenic plant. Detection of its activity is critical to studies on the
      development of various transgenic plants, silence of inserted gene, marker-free
      system development and safety assessment of transgenic food. In this paper,
      several methods for detecting the activity of this enzyme were reviewed.

PMID- 15461290
TI  - [Determination of hydrogenated terphenyls by ultraviolet spectrophotometer in the
      air of work place].
AB  - OBJECTIVE: To determine Hydrogenated terphenyls in the air of work place.
      METHODS: Hydrogenated terphenyls in the air was collected with 40% alcohol
      solution and determined by ultraviolet spectrophotometer. RESULTS: The detectable
      limit was 0.87mg/m3. When the concentration of standard solution was 0 - 20mg/L,
      the relative standard deviation (RSD) was 4.6% - 2.3%. The sampling efficiency
      was 97.3%. The samples were stable for 7 days. CONCLUSION: It was proved that the
      method was fast, simple and accurate. It was suitable for the determination of
      hydrogenated terphenyls in the air of work place.

PMID- 15461292
TI  - [Applications of flow cytometry in toxicological test].
AB  - Flow cytometry (FC) gained attention as a powerful high-throughput and
      multiparameter technology for the analysis of molecular and cell events in
      biological testing. With the developing of the instrument capability and the
      improving of the detection methods. FC has been becoming a more important tool
      both for research and clinical testing practice. FC has also been used in many
      toxicological experiments, which greatly promotes the progress of toxicological
      techniques. In this paper, the recent progress on the flow cytometric approach
      used in toxicological detection was reviewed.

PMID- 15461293
TI  - [Mechanism and prevention measures of gene silencing].
AB  - With the widely application of transgene technology in the fields of high-level
      biologies, more and more attention was payed to gene silence. Gene silence can
      take place at the phase of transcription and post-transcription. With the results
      of methylation, repeated copies and homologous sequence of inner genes, trans
      gene are silenced. There are many kinds of mechanisms of gene silencing and here,
      the mechanisms explaining the gene silence and some prevention measures were
      summarized in this paper.

PMID- 15461294
TI  - [Structural basis of alpha-tocopherol succinate as an antineoplastic agent].
AB  - Alpha-tocopherol succinate is a redox-silent analog of alpha-tocopherol which is
      the major component of vitamin E. Recently, the research findings showed that, as
      a kind of pro-vitamin E, alpha-tocopherol succinate possesses antineoplastic
      activity which alpha-tocopherol lacks of. In this review paper, the link between
      the structure and antineoplastic activity of alpha-tocopherol succinate was
      focused.

PMID- 15461295
TI  - [In vitro alternatives to Draize eye irritation test].
AB  - For reasons of animal welfare and better science, a series of in vitro methods,
      including assays based isolated eye or cornea, Chorioallantoic membrane, cultured
      tissue or cell, had been established and evaluated to replace the Draize eye
      irritation test. This paper provides a brief review of the recent progress in the
      in vitro alternatives to Draize eye irritation test, and the principles of
      scientific validation of these alternatives were also discussed.

PMID- 15461296
TI  - [Development on study of zinc deficiency and immunity].
AB  - In this paper, the progress on study of zinc deficiency and immunity including
      the relationship between zinc deficiency and the apoptosis of T cell, B cell, the
      expression of MT, immunological function of red cell, and non-specific immune
      system were reviewed.

PMID- 15461297
TI  - CT in your clinical practice.
AB  - This report presents the results of a survey of 500 U.S.-based radiologists on
      critical issues associated with the use of CT. The survey represents a
      collaboration between the American Roentgen Ray Society (ARRS) and Philips
      Medical Systems. An outside firm, ICR/International Communications Research,
      conducted the survey. Survey questions were designed to elicit opinions about the
      past, present and future of CT, especially MDCT imaging, in various practice
      environments. Most radiologists (69%) indicated that CT has had a major influence
      on their specialty, more than any other medical advance, and that they expected
      this influence to increase. The idea that MDCT radically improves diagnostic
      quality was not universal, and opinions were mixed about the expansion of CT into
      new applications such as cardiac imaging. A number of concerns were attributed to
      the advent of MDCT and expansion in the number of slices-a phenomenon commonly
      referred to as a "slice war." These concerns revolved around managing the data
      explosion, excessive patient irradiation, bottlenecks in patient throughput, the
      ability of CT staffs to keep up with the rapidly evolving technology and the
      costs of keeping up with these changes. Nevertheless, most radiologists (78%) who
      were surveyed indicated that they used MDCT and that MDCT has had a positive
      effect on their practices in the past five years (90%); most (77%) expected that
      the number of slices would increase by two to 10 times the current level. Fifty
      six percent said that they would be adding one to two scanners to their practices
      in the next five years.

PMID- 15461298
TI  - CT usage.

PMID- 15461299
TI  - The use of PACS.

PMID- 15461300
TI  - Effect of advances in CT on practice.

PMID- 15461301
TI  - Effect of CT on competitiveness, productivity and diagnostic accuracy.

PMID- 15461302
TI  - The future of CT.

PMID- 15461303
TI  - Allocation of financial resources for CT in a practice.

PMID- 15461304
TI  - Allocation of financial resources for CT in the field of radiology.

PMID- 15461305
TI  - Factors warranting increased spending for CT.

PMID- 15461306
TI  - Procedures that may be replaced by CT.

PMID- 15461307
TI  - Prospects for patient procedural volume.

PMID- 15461308
TI  - Achieving greater patient throughput.

PMID- 15461309
TI  - Issues affecting CT.

PMID- 15461310
TI  - Referring physicians' awareness of CT benefits.

PMID- 15461311
TI  - Introduction to sertindole in clinical practice.

PMID- 15461312
TI  - Current issues in schizophrenia: overview of patient acceptability, functioning
      capacity and quality of life.
AB  - The increasing interest in the subjective wellbeing and quality of life (QoL) of
      patients with schizophrenia represents a conceptual extension of therapeutic
      outcome criteria. For a long time, the reduction of positive symptoms alone was
      the most important outcome parameter, but the development of atypical
      antipsychotic drugs in the early 1990s resulted in the adoption of more wide
      reaching measures of therapeutic outcome. Patient satisfaction appears to be
      strongly related to their willingness to be or stay engaged in psychosocial and
      pharmacological treatment, and therefore to the symptomatic and functional
      outcome. Existing studies that deal with QoL and subjective wellbeing differ in
      their methodology and are difficult to compare because of varying underlying
      concepts of QoL or subjective wellbeing, different assessment scales or small
      sample sizes. Although QoL is a heterogeneous concept, it is clearly correlated
      with a number of factors, including illness, medication and stress process
      related variables. Various protective factors have been identified; among these
      are personality traits, the degree of social support and treatment interventions.
      In clinical studies, atypical antipsychotic agents are associated with greater
      improvements in QoL and subjective wellbeing than are conventional agents. The
      reason for this is probably the ability of atypical agents to have a positive
      impact on factors most associated with QoL, such as negative and affective
      symptoms and drug tolerability. The most appropriate clinical approach to
      maximize QoL and subjective wellbeing for patients with schizophrenia is to use
      atypical antipsychotic drugs as a first-line treatment approach. Ideally, an
      atypical drug which is known not to have a negative effect on attention, affect
      or motivation should be chosen.

PMID- 15461313
TI  - A review of the efficacy, tolerability and safety of sertindole in clinical
      trials.
AB  - Sertindole is a non-sedating atypical antipsychotic agent with high selectivity
      for dopaminergic neurons in the mesolimbic system. In pivotal clinical trials,
      sertindole has demonstrated significantly greater efficacy than placebo against
      both the positive and negative symptoms of schizophrenia. In addition, sertindole
      has had at least similar efficacy to haloperidol and risperidone against positive
      symptoms, and significantly greater efficacy than haloperidol and risperidone
      against negative symptoms. The incidence of extrapyramidal symptom (EPS)-related
      adverse events and the rate of medication used to treat EPS in patients receiving
      clinically effective doses of sertindole in clinical trials were similar to those
      observed in placebo recipients and significantly less than those in haloperidol
      recipients. The incidence of QTc interval prolongation of 500 ms or greater with
      therapeutic dosages of sertindole has also been low. In general, sertindole has
      been well tolerated in clinical trials. Unlike other antipsychotic agents,
      sertindole has not been associated with cognitive impairment, and can actually
      improve cognitive function. Observational studies have shown that the efficacy
      and tolerability of sertindole observed in the clinical trial situation are
      emulated in a naturalistic setting. Large cohort analyses (N > 8000) have shown
      that all-cause and cardiovascular mortality is no greater with sertindole than
      with risperidone or olanzapine.

PMID- 15461315
TI  - [Speech understanding in post-lingual adults with cochlear implants].
AB  - It is well recognised that multi-channel cochlear implants are highly effective
      in gaining or regaining auditory perceptual skills of severe to profound hearing
      impaired people. Research shows that adults rapidly improve in speech
      understanding after cochlear implantation. This study reports on speech
      understanding from two Spanish Clinics. 32 post-lingually deafened adults were
      fitted with either a MED-EL COMBI 40 or COMBI 40+ cochlear implant at the
      Hospital Universitario San Cecilio, at the Granada or Hospital Universitario La
      Fe, Valencia Clinic, Spain. Subjects were assessed at 1, 3, 6 and 12 months post
      fitting on a number of speech perception tests. Results showed a highly
      significant improvement on all speech perception tests over the time. These
      ratify other studies in saying that cochlear implantation is a viable and
      successful treatment in post-lingually deafened adults.

PMID- 15461316
TI  - [Geniculate ganglion tumors. Therapeutic and reconstructive management].
AB  - We present five cases of patients diagnosed of a facial nerve tumoral lesion
      localised at the Geniculate Ganglion and all of which underwent surgical
      resection. The initial symptoms were in four cases of peripheral facial nerve
      paralysis and in the fifth case facial paresis. Two trans-mastoid
      extralabyrinthine approaches were performed and one through a combined path
      (middle fossa and trans-mastoid) with reconstruction of the facial nerve through
      a termino-terminal graft. In the fourth case, an approach through fossa media was
      done, and did not include nerve reconstruction but palliative treatment with a
      palpebral gold plaque. In the fifth case, a modified trans-labyrinthine approach
      with facial-hypoglossus termino-terminal anastomosis. Histological diagnosis was
      3 neurinomas and 2 hemangiomas. Of the termino-terminal grafts two managed a
      functional Grade III of the House-Brackmann classification. The third one
      sustained a Grade VI and therefore a suspension with temporal muscle was carried
      out. The patient with facial-hypoglossus anastomosis is in a functional Grade IV.
      Geniculate ganglion tumors are in their majority benign and their treatment is
      the total resection of the tumor. Nerve reconstruction can be primary or deferred
      with the aid of a nerve graft or anastomosis, being necessary palliative
      techniques when resection is not possible.

PMID- 15461318
TI  - [Stapedectomy as day case surgery].
AB  - Day case surgery is increasing and a large proportion of procedures in
      otolaryngology are already being performed as day cases. There is less experience
      in otologic surgery and the reports are specially referred to chronic otitis
      media. A retrospective study of stapedectomy as a day-case procedure is presented
      in this report. The inclusion criteria: anaesthesic risk: ASA I, II or III; if
      the patient has a chronic disease it must be well controlled; they must not have
      postoperative hemorrhagic history; the patient must be accompanied by an adult
      the first 24 hours postsurgery; must have a vehicle; distance to hospital must
      not be more than an hour and they must have a telephone. Between October 1998 and
      December 2002 71 ambulatory stapedectomies were performed in our institution.
      91.2% were discharged home the same day of the procedure. Audiological findings
      obtained six months after surgery that: 87.5% of the patients have an air-bone
      Uda of 10 dB or less.

PMID- 15461319
TI  - [Paranasal sinus osteomas. Revision of 14 cases].
AB  - OBJECTIVE: To present our experience in the management of paranasal sinus
      osteomas. MATERIAL AND METHODS: We review 14 patients with frontoethmoidal
      osteomas removed in our hospital between 1988-2001. The initial symptoms, site
      and size of the lesions, surgical approaches and short and long term
      complications were assesed. RESULTS: The most common symptom in our series was
      headache (57%); most of the tumors were located in frontal (35%) and
      frontoethmoidal (35%) regions with a mean size of 4.2 cm (maximum diameter) at
      the time of surgery. All symptomatic osteomas were resected by classic external
      surgical approaches but two cases were removed by endonasal surgery. DISCUSSION:
      Although osteomas are benign tumors, they may enlarge progressively and produce
      complications. Their resection is not free of risks, so there is some controversy
      about the management of asymptomatic patients. Endonasal surgery reduces the
      morbidity of the treatment but the location and size of the lesions do not allow
      to employ this technique in all cases.

PMID- 15461317
TI  - [Prevalence of the A1555G mutation in the mitochondrial DNA in patients with
      cochlear or vestibular damage due to aminoglycoside-induced ototoxicity].
AB  - OBJECTIVE: To determine the frequency of the A1555G mutation in the mitochondrial
      genome among Spanish patients with aminoglycoside-induced ototoxicity. PATIENTS
      AND METHODS: We screened 25 unrelated cases, totalling 39 individuals with
      cochlear or vestibular damage due to aminoglycoside-induced ototoxicity. This
      group was made up of 18 subjects from 4 unrelated families with a history of
      aminoglycoside ototoxicity in more than one relative, 8 subjects from 8 families
      that also had other relatives with hearing loss in absence of aminoglycoside
      exposure, and 13 sporadic cases. Among the 13 sporadic cases, there were 3
      patients with vestibular involvement. Detection of the A1555G mutation was seen
      by mean of techniques for molecular diagnosis. RESULTS: The A1555G mutation was
      identified in all of the individuals from 4 families with aminoglycoside-induced
      cochlear damage and in 6 of 8 individuals with familial hearing loss. None of the
      sporadic cases carried the mutation. CONCLUSIONS: A high proportion of patients
      with cochlear damage due to aminoglycoside ototoxicity and having a familial
      history of hearing loss, related or not to aminoglycoside exposure, harbor the
      A1555G mutation.

PMID- 15461314
TI  - Case histories illustrating the utility of sertindole in clinical practice.
AB  - Many conventional and atypical antipsychotic agents are available for the
      treatment of schizophrenia. Matching individual patients to the medication that
      suits them best is often a matter of trial and error. Controlled clinical trials
      and extensive post-marketing research have shown that the atypical antipsychotic
      agent sertindole is a broadly efficacious and safe choice for the treatment of
      schizophrenia. Individual case reports emerging from the ongoing sertindole post
      marketing clinical programme illustrate how, under normal conditions of clinical
      practice, a switch to sertindole can benefit patients who have, for various
      reasons, previously not been satisfactorily managed on conventional or other
      atypical antipsychotic agents. Such case reports have shown that a switch to
      sertindole has the potential to provide greater relief from positive, negative
      and affective symptoms than has been achieved with conventional and certain other
      atypical agents. Cognitive dysfunction evident during therapy with conventional
      antipsychotic agents has also been seen to improve in individuals switched to
      sertindole. These improvements have occurred without evidence of extrapyramidal
      symptoms or other poorly tolerated adverse events. After switching to sertindole,
      the five patients described in this report complied well with therapy, were
      generally able to perform daily activities more efficiently, and also had
      improved personal relationships and vocational potential, all of which
      contributed to improvements in their overall quality of life.

PMID- 15461320
TI  - [Evolution study in children with suspected obstructive sleep apnea].
AB  - INTRODUCTION: Obstructive sleep apnea syndrome is a common disorder in childhood
      with an uncertain evolution. OBJECTIVES: Study of children's clinical evolution
      with suspected diagnosis of OSAS, which was carried out after two years of an
      overnight polisomnogram. PATIENTS AND METHODS: 73 children were studied. We
      evaluated if they had been operated and what type of surgery was performed,
      Brouillete Scale and subjective impressions. We have correlated: age, clinical
      evolution and surgery. RESULTS: Age was inversely correlated with changes in
      Brouillete (r=-0.39, p=0.002), standing out that children that underwent surgery
      were younger (4.1 vs. 7.0 years, Student t: -4.22, p=0.00009). Without the
      influence of age, the difference between evolution in operated and not operated
      ones was not significative, statistically speaking, but it was if we analysed the
      different types of surgery by themselves (Snedecor F: 3.9, p=0.007),
      tonsillectomy was the larger. CONCLUSION: The middle-term evolution in children
      with OSAS is good if we use the correct treatment.

PMID- 15461321
TI  - [Second hemithyroidectomy for thyroid carcinoma. Our experience].
AB  - Carcinomas as casual findings can be found in thyroid surgery. After the
      definitive AP result of malignant pathology, if a partial technique was
      performed, we can face problem of completing or not to a total thyroidectomy. We
      are reporting our 12 years experience about reinterventions because a diagnosis
      of thyroid carcinoma (hemithyroidectomies on previous one) was made after an
      anatomopathologic (AP) study on a sample from the first surgery for a supossed
      benign pathology. 18 patients have been studied, all of them were women, 45 year
      old average and we have analysed the initial symptoms, results of basical
      complementary tests, diagnosis AP for first surgery and final result for second
      one. The incidence of malignancy showed in our series after the second
      intervention was 40% so we feel that a total thyroidectomy must be performed
      after a casual finding of thyroid carcinoma, because this allows oncological
      safety and a better control of the patient.

PMID- 15461322
TI  - [Primary nasal tuberculosis: a forgotten disease?].
AB  - Nasal tuberculosis represents a rare manifestation of infection by Mycobacterium
      tuberculosis. Clinically, it appeared to resemble cancer presenting as a
      nasopharyngeal mass with concomitant enlarged lymph nodes. It is important to
      consider tuberculosis in the differential diagnosis of all nasopharyngeal lesions
      and take biopsy samples for histological and bacteriological studies.
      Antituberculosis treatment is satisfactory with standard anti-tuberculous
      chemotherapy. Although this is a rare finding, it should be considered when a
      patient presents with nasal obstruction.

PMID- 15461323
TI  - [Insertion of Montgomery salivary bypass tube under local anesthesia in patients
      with pharyngocutaneous fistula following total laryngectomy].
AB  - Montgomery salivary bypass tube is an effective therapeutic option in the
      treatment of the pharyngocutaneous fistulas following laryngectomy. The original
      insertion technique requires general anesthesia to introduce the tube with direct
      vision of the hypopharynx. In this paper we present an insertion method based in
      the Seldinger technique that allows the placement of the tube under local
      anesthesia in a rapid fashion and well tolerated by the patients.

PMID- 15461324
TI  - Immunohistochemical study of human xanthoma.
AB  - Specimens of human tuberous xanthomas obtained from two hyper-beta
      lipoproteinemic patients were prepared with HE and Sudan III stain and by direct
      immunofluorescence with fluorescein isothiocyanate labeled antihuman beta
      lipoprotein rabbit serum. In some histiocytes and foam cells in early stages,
      lipids were stained in granular patterns and specific fluorescence was observed.
      In some foam cell nests, specific fluorescence was weak or absent, and orange
      colored lipid autofluorescence was present. The foam cells in such nests were
      probably late foam cells and corresponded to the large cytoplasmic foam cells
      stained densely and amorphously for lipids. It was concluded that at early stages
      of xanthoma formation, serum lipoproteins were incorporated into dermal
      histiocytes and early foam cells. The apoproteins of the incorporated
      lipoproteins were probably degraded and lipid residues accumulated in the cells.
      Specimens of tuberous xanthoma covered by plane xanthoma showed lipids and bright
      specific fluorescence at the basement membrane zone. A faint fluorescence was
      observed in the upper dermis and even in parts of the epidermal intercellular
      spaces.

PMID- 15461325
TI  - Phenylalanine hydroxylase deficiency in the peripheral lymphocytes from
      phenylketonuria.
AB  - A radiograph of the incorporation of 3H-phenylalanine and 3H-tyrosine into
      cultured lymphocytes in a phenylketonuria patient indicates phenylalanine
      hydroxylase deficiency in the peripheral lymphocytes. Cultured lymphocytes from
      the patient showed much less uptake of 3H-phenylalanine and a slightly higher
      incorporation of 3H-tyrosine than the control. It is possible that a lack of
      phenylalanine hydroxylase in the peripheral lymphocytes of PKU patients prevents
      oxidation of phenylalanine to tyrosine.

PMID- 15461326
TI  - Orthopedic symptoms in pustular bacterid (pustulosis palmaris et plantaris):
      Tietze's syndrome and arthritis of manubriosternal joint due to focal infection.
AB  - Painful orthopedic symptoms in the sternal area, such as arthritis of the
      manubriosternal and sternoclavicular joint or Tietze's syndrome, were found in 14
      of 132 cases of pustulosis palmaris et plantaris. The majority of the pustulosis
      palmaris et plantaris patients with orthopedic symptoms had skin eruptions not
      only on the palms and soles, but also on the backs of the hands and feet, the
      arms, the legs and the trunk. Such cases were usually accompanied by elevation of
      the erythrocyte sedimentation rate, leucocytosis, changes in serum globulin, and
      also pyrexia at the time of exacerbation. The skin and orthopedic symptoms often
      worsened after acute exacerbation of the focal infection, and occasionally
      responded to tonsillectomy or chemotherapy with antibiotics, which is suggestive
      of the probable cause of the bacterid.

PMID- 15461327
TI  - Tissue fibrinolytic activity of allergic contact dermatitis.
AB  - One of our co-workers was sensitized with a 1% DNCB solution in acetone. Biopsies
      were obtained from skin lesions 1, 2, 4, 8, 12, 24, 30, 36 and 48 hours after a
      challenge with 0.1% DNCB solution. In the upper dermis, a rapid decrease of
      tissue fibrinolytic activity was found which disappeared after 30 hours. In the
      lower dermis, biphasic changes were observed. Tissue fibrinolytic activity
      increased one hour and 12-36 hours after challenge, whereas at 48 hours, when
      erythema was most intensive, it decreased in comparison to the normal activity.
      Erythema and histological changes of the epidermis and the dermis appeared after
      approximately 12 hours. As for lymphocytes, T-cells were seen at first.
      Furthermore, B-cells were noted after approximately 30 hours when marked
      infiltration began to appear.

PMID- 15461328
TI  - Staphylococcal scalded skin syndrome. II. Serum level of anti exfoliatin and anti
      alpha-toxin in patients with staphylococcal scalded skin syndrome or bullous
      impetigo.
AB  - In order to study the differences between staphylococcal scalded skin syndrome
      (SSSS) and bullous impetigo, the anti exfoliatin level was assessed in the sera
      from both groups of patients, and no significant difference in the level was
      found. However a significant difference was noted in the anti alpha-toxin levels
      in sera from both group of patients; that of SSSS patients was much lower than
      that of impetigo patients and of children in a control group. Five out of 6
      patients with SSSS showed an unchaged level of anti alpha-toxin at the second
      examination, while an increased anti exfoliatin level was noted in 4 out of 6
      SSSS patients.

PMID- 15461329
TI  - Dermatitis gangrenosa infantum.
AB  - A case of a 4-month-old girl with dermatitis gangrenosa infantum is reported. The
      lesions were seen on the cheeks and later at the site of blood examination on the
      earlobes. The patient was successfully treated with antibiotics and then by skin
      grafting.

PMID- 15461330
TI  - A case of minocycline-induced fixed drug eruption.
AB  - A case of fixed drug eruption induced by minocycline on the glans penis of a 26
      year-old man is reported. Later oral administration of minocycline reproduced the
      same type of eruption, but tetracycline, possessing the same starting structure
      as minocycline, did not induce the eruption. Laboratory findings were normal.
      This seems to be the first case of fixed drug eruption induced by minocycline to
      appear in the literature.

PMID- 15461331
TI  - Xanthoma-inducing beta-lipoprotein immune complexes.
AB  - Untreated rabbits and rabbits sensitized with human beta-lipoproteins were
      intracutaneously injected with either human or rabbit beta-lipoproteins (2 mg as
      protein). Forty-eight hours later, at the human beta-lipoprotein injection site,
      dense cell infiltrations stood out sharply demarcated from the surrounding
      region. The infiltrating cells were composed of polymorphonuclear cells, nuclear
      dust and histiocytes. Foam cell nests were observed in sensitized rabbit dermis
      one week after human beta-lipoprotein injection. Direct immunofluorescence
      employing fluorescein isothiocyanate labeled antihuman beta-lipoprotein antiserum
      showed that the injected human beta-lipoproteins were incorporated into the
      infiltrating cells of sensitized rabbit dermis up to 48 hours after injection.
      Specific fluorescence was greatly reduced but lipid autofluorescence remained in
      mature foam cells. During the 3-week examination period, no trace of foam cell
      nests was found at the site of human beta-lipoprotein injection on non-sensitized
      rabbits. Intracutaneous rabbit beta-lipoprotein injection revealed no histiocytic
      infiltrations in either sensitized or non-sensitized rabbits. These findings
      indicated that intracutaneously injected human beta-lipoporteins were
      incorporated into rabbit dermal histiocytes more easily in aggregated immune
      complex form than in their natural state. These histiocytes were easily
      transformed to foam cells. Apoproteins of the incorporated lipoproteins were
      degraded, and lipid residues accumulated in mature foam cells.

PMID- 15461332
TI  - Erythropoietic protoporphyria--report of a family and clinical review.
AB  - Three cases of erythropoietic protoporphyria are reviewed. The three patients
      constitute members of one family. The protoporphyrin content of the red blood
      cells was high, but porphyrins and their precursors in the urine and faeces were
      not excessive. Other normal members of the family did not reveal high
      protoporphyrin content in the red blood cells. Clinical symptoms were itching,
      swelling, shallow depressed scars and waxy yellow discoloration on the face and
      brown pigmentation and thickness on the back of the hands after exposure to the
      sun. The microscopic findings from skin biopsy specimens of the lesions resembled
      changes of the lipoid proteinosis.

PMID- 15461333
TI  - Heliotherapy of pityriasis lichenoides chronica.
AB  - Fifteen patients with pityriasis lichenoides chronica (parapsoriasis guttata)
      were treated with sunlight irradiation during the summer months at seaside
      resorts under the supervision of the authors. Complete clearing occurred in 1 of
      the patients, almost complete clearing in 8, definte improvement in 4, temporary
      clearing in 2. All patients responded beneficially and no worsening was noted in
      these 15 cases. In an additional six cases who were instructed to expose
      themselves to sunlight similar results were obtained.

PMID- 15461334
TI  - A case of lichen myxedematosus associated with immunological abnormalities.
AB  - A 33-year-old male consulted us with symptoms of band-like infiltration,
      thickenning and subcutaneous induration occurring in the face, chest, back,
      shoulder and upper extremities. In the following time he developed arthralgia,
      fever and ocular symptoms. Laboratory tests revealed normal thyroid functions and
      a normal bone marrow picture, but there were immunological abnormalities such as
      reduced cellular immunity, decrease in C 3 (beta 1c/la) and positive antinuclear
      antibody. Histologically, there was an increase in fibroblasts and deposits of
      hyaluronic acid were revealed histochemically. A diagnosis of lichen
      myxedematosus was established. At present, all symptoms and signs including skin
      rash have disappeared following corticosteroid therapy and the patient is being
      followed up. So far as we have been able to trace, reports on lichen
      myxedematosus associated with immunological abnormalities as described here have
      not been found. The relationship between this pathology and immunological
      abnormalities are discussed.

PMID- 15461335
TI  - A peculiar acantholytic dermatosis.
AB  - This paper reports a peculiar case seen in a 36-year-old woman who every summer
      since the age of 30 has developed numerous solitary vesicles or crusted papules
      with intense pruritus in the seborrheic zones. There are no general symptoms and
      no hereditary relations. The individual rash disappears completely in a week to a
      month and there is no eruption in winter. The clinical picture resembles that of
      Darier's disease, but histopathological tests reveal intraepidermal cleft or
      bulla formation due to acantholysis but no dyskeratosis. Clinicopathological
      consideration indicates a disease akin to familial benign chronic pemphigus, but
      as our case does not correspond to any known disease, it is therefore reported as
      a peculiar acantholytic dermatosis.

PMID- 15461336
TI  - Exfoliative dermatitis from Chinese herbs (decoction)--an example of purely
      epidermal contact-type hypersensitivity to ingested medicines.
AB  - A patient, aged 78, with exfoliative dermatitis due to the ingestion of Chinese
      herbs (decoction) was presented. Provocative medication showed that he was
      sensitive to 4 composite materials (Radix angelicae acutilobae, Rhizoma
      zingiberis, Radix paeoniae and Radix glycyrrhizae). Patch tests were positive to
      each of these materials while the intradermal test was negative. These results
      indicate that systemic contact-type hypersensitivity to the ingested medicines is
      involved in evoking the exfoliative dermatitis lesion and that, in addition,
      purely epidermal contact sensitivity as defined by S. Epstein and Baer plays an
      important role.

PMID- 15461337
TI  - Colloid degeneration of the skin--a case report.
AB  - A patient with multiple nodules on the chin and scalp is presented.
      Histologically, the nodules were composed of amorphous materials which also
      completely filled up the whole dermis. Histochemical observation indicated that
      the amorphous material in the nodule was a kind of glycoprotein. Electron
      microscopic examination revealed that the material consists of short wavy
      fibrils, 60 to 100 A in diameter, and of a low electron-dense amorphous
      substance. Biochemical examination supported the view that the amorphous material
      is so-called sialomucoid. The nodules were finally diagnosed as colloid
      degeneration of the skin (nodular type).

PMID- 15461338
TI  - Immunological aspects of staphylococcal skin infection.
AB  - Patients with staphylococcal infection of the skin were examined for
      immunological status. All cases examined in the present study had gamma-globulin
      levels within the normal range. The proliferative response of peripheral blood
      lymphocytes to staphylococcal antigen was significantly depressed in patients
      with furunculosis as compared with that in patients with common furuncle or in
      healthy controls. All patients with furunculosis showed higher titers of anti
      Staphylococcus aureus antibody than did those with furuncle. The dissociation
      between cellular and humoral immunity in furunculosis seems to be explained in
      terms of immune deviation.

PMID- 15461339
TI  - Electron microscopic observations on the lesions of herpes zoster with topical
      application of interferon.
AB  - The lesions of herpes zoster in three patients were investigated electron
      microscopically before and after topical application of interferon. In the
      blister, on the 5th to 7th day after its formation, the following were seen:
      acantholytic cells with virus particles in the nucleus and cytoplasm,
      multinucleated cells derived from keratinocytes, edematous and degenerated
      keratinocytes containing virus particles and tonofibrillar materials, macrophages
      with many large vacuoles, neutrophils, lymphocytes and Langerhans's cells. After
      the first application of interferon, the findings for keratinocytes were the same
      as those of before application and keratinocytes were frequently found adjacent
      to macrophages. The macrophages were large and had numerons large vacuoles in the
      cytoplasm. After the second application of interferon, virus particles were often
      seen in the vacuoles of the macrophages in comparison with that before
      application. In the cytoplasm of macrophages, acantholytic keratinocytes and
      tonofibrillar materials were phagocytized. Many virus particles were seen in the
      vacuoles of some acantholytic keratinocytes. It was concluded from these findings
      that the macrophages accelerated the phagocytotic activity of the virus
      particles.

PMID- 15461340
TI  - The effects of castration and testosterone administration on mast cells and
      hydroxyproline in rat skin.
AB  - In rat skin of both sexes, significantly higher concentrations of mast cells were
      observed in the genital area as compared with the skin of the back. The
      hydroxyproline (HPL) value in the preputial skin was half that in the dorsal
      skin. The influence of castration and the administration of testosterone on male
      rat skin mast cells and HPL were investigated. A possible relationship was
      pointed out between HPL value and the mast cell population of the skin.

PMID- 15461341
TI  - Nevus cells observed in the sebaceous glands.
AB  - Of sebaceous gland-containing specimens of melanocytic nevi, a total of 79
      specimens from 70 cases of nevocellular nevus (consisting of 10 cases of compound
      nevus and 60 of intradermal nevus), four cases of juvenile melanoma and three of
      blue nevus were examined light-microscopically in detail for the presence or
      absence of nevus cells or dermal melanocytes in the sebaceous glands. As a
      result, clusters of cells that appeared to be nevus cells were found in the
      sebaceous glands of specimens from a total of three cases, that is, two cases of
      nevocellular nevus i.e. compound nevus, and one of the cases of juvenile
      melanoma. Two cases were infantile and one case was the age of puberty. The
      origin of the nevus cells found in the sebaceous glands is discussed.

PMID- 15461342
TI  - Erythrokeratodermia variabilis.
AB  - The case of a 10 year-old Japanese boy with erythrokeratodermia variabilis is
      reported in addition to a review of the Japanese literature. The patient was
      first examined in our clinic on October 21, 1965, because of generalized
      hyperkeratotic lesions and erythematous lesions which had persisted since he was
      3 months old. Hyperkeratotic and verrucous lesions were noted on his auricles and
      trunk, on which there were also sharply demarcated erythematous lesions of
      various sizes and shapes which were not elevated from the adjacent skin.
      Laboratory findings were within normal limits. Histopathological examination
      revealed a remarkable hyperkeratosis with a basket weave appearance, moderate
      acanthosis and a slightly thickened granular layer. Polyethylenglycol 400 and
      corticosteroid ointment were slightly beneficial to the hyperkeratotic lesions.

PMID- 15461343
TI  - Purine phosphoribosyltransferase activities in guinea pig epidermis.
AB  - Purine phosphoribosyltransferase activities in normal and experimental
      hyperkeratotic epidermis of guinea pig skin were demonstrated quantitatively by a
      new microassay method. The ratio of HGPRTase with hypoxanthine as a substrate to
      APRTase activity in normal and hyperkeratotic epidermis was found to be 0.94 and
      0.60, respectively. The HGPRTase and APRTase activities expressed as micromoles
      per gram wet weight per min. were increased in experimental hyperkeratotic
      epidermis and it is suggested that the salvage pathway for purine nucleotide
      biosynthesis is activated in experimental hyperkeratotic epidermis. The pH
      optimum of these enzymes and their stability in the frozen state were also
      demonstrated.

PMID- 15461344
TI  - Severe pyoderma following corticosteroid occlusion.

PMID- 15461345
TI  - Evaluation of tonsillectomy as a treatment for pustulosis palmaris et plantaris.
AB  - Two hundred and eighty five cases of pustulosis palmaris et plantaris (PPP), of
      which 73 cases (25.6%) underwent tonsillectomy, were studied to evaluate the
      effectiveness of tonsillectomy as a treatment for PPP. The group of
      tonsillectomized patients showed significantly better results than a group which
      received other methods of treatment. A tendency to leukocytosis was observed in
      PPP which normalized, in many cases, after tonsillectomy. The shorter the period
      between the onset of PPP and tonsillectomy the better the results, and the
      quicker the response. A transient worsening of PPP after tonsillectomy did not
      after the prognosis. In order to determine if tonsillectomy was indicated, an
      ultrashort wave direct provocation test was conducted in which ultrashort wave
      was applied to the tonsil. Leukocytosis and worsening of PPP after the test was
      considered as an indication for tonsillectomy. In some cases, there were
      considerable changes in plasma cortisol levels and NBT test values after the
      provocation test. Improvement of PPP after the Impretol test (one of the
      annulation tests) in which Impretol was injected into the tonsil, appears to
      support the focal infection origin of PPP in these cases. There is a possibility
      that the Impretol test could be used as a treatment for PPP.

PMID- 15461346
TI  - Pityriasis lichenoides et varioliformis acuta immunohistopathologic study.
AB  - Immunoglobulin M and complement (Clq, C3 and C9) were found to be deposited
      together in the walls of affected blood vessels and also in the basement membrane
      zone of skin lesions from two patients with pityriasis lichenoides et
      varioliformis acuta (PLVA). The fluorescence appeared to be most intensely
      distributed in blood vessels which were affected by inflammatory infiltrates and
      frequently showed hyaline or fibrinoid changes of their walls. Deposits of C3
      activator, fibrin and albumin were not observed. These findings suggest that the
      disease process in PLVA is the result of a vasculitis mediated by an immune
      complex and possibly by activation of the classical complement pathway. In
      addition, serum IgM was slightly increased in both patients.

PMID- 15461347
TI  - Composition and mechanism of deposition of the intercellular substance in
      parakeratotic psoriatic epidermis.
AB  - In order to elucidate both the mechanism of deposition and the composition of the
      substance that is observed mainly the intercellular spaces (ICS) and to a lesser
      extent in the cytoplasm of psoriatic epidermis, five cases of psoriasis vulgaris
      were examined using conventional histology and histochemistry, electron
      microscopy, and direct immunofluorescence technique with or without incubation in
      acid citrate buffer or digestion by fibrinolysin. The substance was found by
      electron microscopy to be rather dense and finely granular, and that in the
      parakeratotic horny layer was diastase-resistant PAS positive, and showed
      positive immunofluorescence for immunoglobulins, complement, and fibrinogen. The
      fluorescence was not significantly altered by pre-incubation of the tissue
      sections in acid citrate buffer, but was significantly diminished by predigestion
      of tissue sections with fibrinolysin. From these findings, we concluded that the
      substance is likely to consist of and be derived from the components of plasma
      protein, and to play a role in the formation of the parakeratotic psoriatic horny
      layer. It also seems that the deposition of this substance is rather the result
      of the coagulation of plasma protein than that of antigen-antibody reactions.

PMID- 15461348
TI  - Unspecific increase of antistreptolysin-O titer in acute guttate psoriasis.
AB  - An acute streptococcal infection is well-known to be a predisposing factor in
      acute guttate psoriasis. This study also revealed a high ASO titer in 11 of 13
      patients at first examination. However, a non-specific ASO increase due to non
      immunological reaction of serum lipoproteins with antistreptolysin-O, was found
      in 5 of these patients who visited our clinic at the evolving phase, 2 or 3 weeks
      after onset of the eruption but was no longer observed at 5-6 weeks and
      thereafter. On the other hand, specific ASO increase, which was not related to
      lipoproteins, was observed first in some patients at 3-4 weeks and at 7-10 weeks
      in all patients examined. These observations suggest the role of streptococcal
      lipoprotein alteration in the occurrence of this disease.

PMID- 15461349
TI  - A study on the characterization of Corynebacterium acnes.
AB  - Forty-nine strains of anaerobic gram-positive rods were used in a systematic
      study of their biochemical and physiological reactions and morphological
      characteristics and were also subjected to gas chromatographic analyses in an
      effort to classify them as strains of Corynebacterium acnes (C. acnes). The
      strains were isolated both from lesions in acne vulgaris and from normal skin.
      According to their biochemical and physiological characters, these 49 strains
      were divided into six subgroups (Subgroup A-F). They were also separated into two
      morphological types. The larger of these two types included gram-positive,
      unevently staining pleomorphic rods (35 strains); the smaller type contained
      shorter coccal rods similar to Peptostreptococci (14 strains). The macroscopic
      appearance of the colonies of both types was the same. All strains of the smaller
      type showed the same biochemical and physiological characteristics which were of
      the saccharolytic type (Subgroup B) suggesting a close relationship between the
      microscopic appearance of the strains and their biochemical and physiological
      characteristics. Upon microscopical observation, the changing the pH of the media
      did not cause any transformation of the organism from one type to another.
      Between pH 6.0 and 6.5 all strains grew well but above pH 8.0 growth was poor.
      The gas chromatographic analyses demonstrated that selected sample strains from
      each of the six subgroups showed the same characteristic chromatograph,
      suggesting that they could be of the same species, i.e., C. acnes.

PMID- 15461350
TI  - A case of Schonlein-Henoch-purpura: an immunopathological study.
AB  - A case of Schonlein-Henoch-purpura is presented. The immunofluorescent study of
      skin lesions of the patient showed granular deposits of IgA and C3 in the blood
      vessel walls perivascular deposits of plasminogen and diffuse localization of
      fibrin and fibrinogen in the upper dermis. Complement activation via the
      alternative pathway through IgA, C3 and plasminogen deposits was suggested.

PMID- 15461351
TI  - A case of eosinophilic lymphfolliculosis of the skin (Kimura's disease).
AB  - Eosinophilic lymphfolliculosis of the skin (Kimura's disease) in a 31-year-old
      male is reported. He had two subcutaneous tumors, 10 x 9 x 3 cm and 9 x 7 x 2 cm
      in size, in the right retroauricular and submaxillary areas respectively.
      Histopathologic examination of the tumors showed marked infiltration of
      eosinophils, mast cells and lymphocytes, and angiomatous proliferation of blood
      vessels from the dermis to the skeletal muscular tissue. In subcutaneous adipose
      tissue, there were numerous lymphfollicles with germinal centers in which IgE
      deposition with reticular appearance was observed by immunofluorescent technique.
      Study of the peripheral blood showed marked eosinophilia and an increase of serum
      IgE level. These findings suggest the possibility that Type 1 allergic reaction
      may be involved in the histogenesis of eosinophilic lymphfolliculosis of the
      skin, although there is no direct evidence for the existence of antigens which
      react to IgE antibody in the skin lesion.

PMID- 15461353
TI  - An ultrastructural observation of intracytoplasmic desmosomes in Darier's
      disease.
AB  - In a typical case of Darier's disease, intracytoplasmic desmosomes, gap junctions
      and many vesicles were observed in the cytoplasm of epidermal keratinocytes.
      Intracytoplasmic desmosomes were found in the cytoplasm of the excessively
      keratinized cells, vacuolated cells and acantholytic cells. They were not
      associated with tonofilaments as much as with ordinal intercellular desmosome
      tonofilament complexes, and some of them lacked a central strip and looked
      similar to the denatured intercellular desmosomes in the morphology of the
      abnormal keratinocytes of Darier's disease. These intracytoplasmic desmosomes
      were long and undulating and some of the showed a "tennis racket" image (Caputo).
      Furthermore, some were combined with the gap junction and the intermediate
      junction, forming a bounded vesicle in the cytoplasm.

PMID- 15461352
TI  - Evaluation of RAST in atopic dermatitis.
AB  - Eighty-two patients with atopic dermatitis were examined for specific IgE
      antibodies by RAST. A higher number of positive RAST reactions were found in
      patients with high serum IgE values and with coexisting asthma and/or allergic
      rhinitis. Positive RAST reactions against mite and house dust were found in many
      of these patients and even in about one-half of patients with atopic dermatitis
      only. The comparisons between intradermal tests and RAST were made with various
      allergens and the mite extract showed the best agreement between these two tests.

PMID- 15461354
TI  - Treatment of mycosis fungoides with OK-432.
AB  - Up to the present no other therapeutic means besides local X-ray or beta-ray
      irradiation and anticancer drugs for the treatment of patients with mycosis
      fungoides, especially when the condition has progressed to secondary involvement
      of the lymph nodes, has been found. A recent clinical trial of OK-432 injected
      locally into cutaneous tumors of a patient with this disease resulted in a
      conspicuous contraction not only of the tumors injected but of other tumors as
      well along with significant regression of lymphadenomas. No serious adverse
      reaction was observed other than low-grade fever and heavy-headedness. These
      results suggest host-mediated and direct antitumor effects of OK-432 as the
      possible underlying mechanisms. The efficacy of OK-432 in reducing the size of
      the tumors without causing any serious adverse effects indicate the potential
      usefulness of this drug for the treatment of mycosis fungoides.

PMID- 15461355
TI  - Inactivation mechanism of tyrosinase in mouse melanoma.
AB  - Tyrosinase [EC 1.14.18.1] isolated from mouse melanoma was inactivated during the
      dopa-tyrosinase reaction. When ascorbate was added to the reaction system, in
      which dopa-quinone is immediately converted back to dopa by ascorbate thus
      preventing the formation of melanin, tyrosinase inactivation similarly occurred.
      If superoxide anions (O2-) or singlet oxygens (1O2), are generated during the
      reaction they can attack the enzyme protein to be inactivated. Therefore an
      estimate was made with scavengers for oxygen radicals and with a liquid
      scintillation counter but neither was detectable. Thus the inactivation involved
      is not due to reaction products nor oxygen

PMID- 15461356
TI  - Studies on the dinitrophenylated lymphocytes in guinea pig painted with DNCB.
AB  - The number of DNP group-bearing lymphocytes in the regional lymph node, thoracic
      duct and peripheral blood was determined at various time intervals after painting
      normal guinea pigs with DNCB by the immunofluorescent method using anti-DNP
      antibody. The incidence of such cells in the regional node was maximal at 12
      hours whereas in the thoracic duct and peripheral blood the maximum incidence was
      found at 0.1-2 hours after painting. Unreacted DNCB was demonstrated in both the
      thoracic lymph duct and the blood at least for 12 or 24 hours respectively
      following exposure to DNCB. The authors therefore suggest that DNCB reacts
      directly in vivo with the lymphocyte cell membrane of guinea pig following
      epicutaneous application of the chemical.

PMID- 15461357
TI  - Angiolipoma in brothers.
AB  - Two brothers with angiolipoma are presented. The patients, 33- and 37-year-old
      men, have multiple subcutaneous nodules on the trunk and extremities. Skin
      biopsies have confirmed the diagnosis of angiolipoma.

PMID- 15461358
TI  - Clinical course of atrophie blanche.
AB  - Lesions of atrophie blanche which developed in 2 patients with systemic lupus
      erythematosus have been followed up for 3 years. The observation was made that
      atrophie blanche was not always preceded by ulcers but healed directly as scars.
      It was assumed that atrophie blanche might not be a terminal stage of necrotizing
      angitis but an intermediate one in the healing process.

PMID- 15461359
TI  - Part B premium for 2005 will rise by 17.4 percent...

PMID- 15461360
TI  - Perspectives. Bad news on private coverage, good news--for now--on public.

PMID- 15461361
TI  - Collaborating to tackle the problem of anthelmintic resistance.

PMID- 15461362
TI  - Survey of condition-based prescribing of antimicrobial drugs for dogs at a
      veterinary teaching hospital.
AB  - A database of the prescriptions of antimicrobial drugs for the treatment of
      common infectious diseases in dogs at the Finnish Veterinary Teaching Hospital
      was searched to determine to what extent national guidelines were being followed.
      Twenty-two per cent of 5918 dogs were treated orally with antimicrobial drugs.
      The most commonly used drugs were beta-lactams (49 per cent) of which cephalexin
      and amoxycillin-clavulanate were most widely prescribed. The usage of
      fluoroquinolones was only 2.8 per cent. The prescription of antimicrobials for
      pyoderma was contrary to Finnish guidelines, but the use of cephalexin or
      amoxycillin-clavulanate as first-line drugs instead of macrolides or lincosamides
      or trimethoprim-sulphonamides was acceptable because of the presence of
      resistance by canine staphylococci. The drug most commonly used to treat acute
      urinary tract infections was trimethoprim-sulphonamide, in agreement with the
      guidelines. Antimicrobial drugs were used excessively after surgical procedures,
      and for treating acute gastrointestinal disturbances and small wounds and
      traumas.

PMID- 15461363
TI  - Investigation of calf health and welfare on dairy farms in south-west England.
AB  - A questionnaire was designed to investigate calf health and welfare on dairy
      farms in the south west of England with regard to the degree of compliance with
      the Welfare of Farmed Animals (England) Regulations 2000. The level of veterinary
      involvement in calf rearing and management on dairy farms in the south west of
      England was also assessed. The questionnaire was sent to 32 large animal
      practices in the catchment area of the Veterinary Laboratories Agency--Langford.
      Compliance with the regulations was found to be variable. The requirements for
      the isolation of sick calves, provision of bovine colostrum within six hours of
      birth, the provision of fresh, clean water and restrictions concerning tethering
      were not well complied with. However, the requirements for twice-daily feeding
      and inspection, visual and tactile contact between calves, access to forage and
      the provision of clean, dry bedding were well complied with. The results also
      suggested that there was some lack of veterinary input into the health and
      welfare of calves on dairy farms visited by the practices routinely and non
      routinely.

PMID- 15461364
TI  - Comparative haematology and blood chemistry of endangered lizards (Gallotia
      species) in the Canary Islands.
AB  - Blood samples were taken from the ventral coccygeal vein of 15 El Hierro giant
      lizards (Gallotia simonyi) (seven females and eight males), six La Gomera giant
      lizards (Gallotia bravoana) (four males and two females) and four Tenerife giant
      lizards (Gallotia intermedia) (two males and two females), and 31 blood
      parameters were measured. Among the haematological parameters there were
      significant differences between the three species in heterophils, azurophils and
      lymphocytes, but no significant differences in red blood cell count, white blood
      cell count, haemoglobin, packed-cell volume, monocytes, eosinophils and
      basophils. In terms of blood chemistry there were significant differences between
      the three species in cholesterol, triglycerides, glucose, sodium, chloride, urea,
      uric acid, total proteins, prealbumin, albumin and gamma globulins, but no
      significant differences in calcium, potassium, aspartate aminotransferase,
      alanine aminotransferase, creatine kinase, bile acids, alpha-1 and alpha-2
      globulins and beta globulins.

PMID- 15461365
TI  - Survey of clinical problems identified in pet pigs in the UK.

PMID- 15461366
TI  - Clinical and computed tomographic findings in a heifer with vestibular syndrome
      caused by bullous empyema.

PMID- 15461367
TI  - Hydropericardium syndrome in Japanese quail (Coturnix coturnix japonica).

PMID- 15461369
TI  - Nandrolone metabolites in racing greyhounds.

PMID- 15461368
TI  - Problems associated with twin pregnancies in dairy cows.

PMID- 15461370
TI  - CLA survey in Scotland.

PMID- 15461371
TI  - Diagnostic anaesthesia of the equine lower limb: a comparison of lidocaine and
      lidocaine with epinephrine.
AB  - The anaesthetic potency, onset of action, duration of action, and side effects of
      lidocaine and lidocaine plus epinephrine for proximal metacarpal block of the
      lateral and medial palmar nerves were determined. Ten horses were used and legs
      were injected using a cross-over model with three test solutions: 1) solvent and
      lidocaine (2%) plus epinephrine (SLE); 2) solvent and lidocaine (2%) without
      epinephrine (SL); and 3) solvent only (S). The contra-lateral leg was injected
      with saline (placebo; P). In both the SL and SLE groups, the onset of anaesthesia
      occurred between 5 and 15 minutes after injection. In the SL group the effect was
      short-lived, lasting 60 minutes, with a maximum effect at 15 minutes. SLE induced
      long-lasting anaesthesia in most animals moderate or total anesthesia lasted 6
      hours, and in two horses more than 9 hours. The maximum effect was achieved at 60
      and 90 minutes. Swelling, the main side effect, was seen halfway between the
      injection site and the fetlock joint. Swelling on day 1 was minimal in the legs
      injected with P (105.3%) but was progressively greater with S (129%), SL (136%),
      and SLE (172%). On day 1 and day 2 the differences between SLE and SL, and
      between SLE and S were significant (P < 0.05). The difference between S and SL
      was not significant. On day 3, the swelling had subsided and differences were no
      longer significant.

PMID- 15461372
TI  - [Help when helping].

PMID- 15461373
TI  - [Do consumers trust their food?].

PMID- 15461374
TI  - [Predecessors: veterinarians from earlier times (55). Daniel Elmer Salmon (1850
      1914)].

PMID- 15461375
TI  - [Severe adverse effects of certain veterinary drugs in collies and collie-like
      dogs].

PMID- 15461376
TI  - [Efficient negotiating, how a cow catches a rabbit].

PMID- 15461377
TI  - [West Nile virus also in the Netherlands?].

PMID- 15461378
TI  - [More clarity about the new law pertaining domestic animal travel and the EU
      passport].

PMID- 15461379
TI  - [Veterinary 'rights'].

PMID- 15461380
TI  - [Avian influenza and reality].

PMID- 15461381
TI  - [Henriette Vrieling veterinarian-dentist].

PMID- 15461382
TI  - [Motion during general meeting KNMvD on October 1, 2004. BPL (Belangengroup
      Practiserende Dierenartsen) wants to join KNMvD membership interest group
      employees/employers].

PMID- 15461383
TI  - Antigenic mixture of synthetic peptides for the immunodiagnosis of HTLV I/II
      infection.
AB  - Monomeric and chimeric synthetic peptides were used as coating antigens in four
      different mixtures in a solid phase immunoassay to select an optimal combination
      for the detection of antibodies to human T-cell lymphotropic virus (HTLV) in
      serum samples. The peptides, P-13 (gp21 I), Q5 (gp21 II)-GG-(gp46 II), and Q
      (gp46 I)-GG-(p19 I), represent immunodominant sequences from transmembrane
      protein (gp21), envelope protein (gp46), and core protein (p19) of HTLV I/II
      viruses; they were the most antigenic and specific peptides in previous studies.
      The sequences of the chimeric peptides were separated by two glycine residues. An
      indirect UltramicroEnzyme-linked immunosorbent assay (UMELISA) was used to
      evaluate the antigenicity of these peptide mixtures by using samples from anti
      HTLV I/II PRP205(M), (n = 20), HTLV I-infected individuals from Cuba (n = 7), and
      HTLV I-positive sera from Colombia and Chile (n = 9). The specificity was
      evaluated with healthy blood donor sera (n = 300), anti-HIV 1-positive samples (n
      = 10), and other seropositive samples to different infectious agents. The highest
      sensitivity and specificity was obtained with mixture 1, which could be very
      useful in the immunodiagnostic of HTLV infection.

PMID- 15461384
TI  - Incorporation of different bridge length linkers in enzyme and its use in the
      preparation of enzyme conjugates for immunoassay.
AB  - An enzyme horseradish peroxidase (HRP), as a starting material, has been used to
      introduce different bridge length linkers, and its use in the preparation of
      enzyme conjugates for immunoassay is described. HRP was conjugated to adipic acid
      dihydrazide (ADH), gamma amino butyric acid (GABA), followed by ADH and 6-amino
      caproic acid (6ACA) followed by ADH. The different bridge length linkers
      incorporated enzyme was coupled to a carboxylic derivative of cortisol. Four
      enzyme conjugates with different bridge length were prepared, such as cortisol-21
      hemisuccinate-HRP (cortisol-21-HS-HRP), cortisol-21-HS-ADH-HRP, cortisol-21-HS
      ADH-GABA-HRP, and cortisol-21-HS-ADH-6ACA-HRP. The influence of linker on
      sensitivity and specificity of the cortisol assay was studied. The study revealed
      that incorporation of a linker between hapten and enzyme increases the
      sensitivity and specificity of the assay.

PMID- 15461385
TI  - Enzyme-linked immunosorbent assay detection of microcystins using new monoclonal
      antibodies.
AB  - New monoclonal antibodies (mAbs) against the microcystin-leucine-arginine variant
      (microcystin-LR), a cyclic peptide toxin of the freshwater cyanobacterium
      Microcystis aeruginosa, were prepared from cloned hybridoma cell lines. Using
      these mAbs, an enzyme-linked immunosorbent assay (ELISA) experiment was made for
      the detection of cyanobacterial hepatotoxins, microcystins in water sampled in
      Soyang Lake, Korea. The performance of the ELISA test with mAbs established in
      this study was evaluated. The ELISA detection was compared with HPLC detection.
      Since the detection limit of HPLC is several orders of magnitude higher than with
      ELISA, attention was also paid to concentration of samples with solid phase
      extraction cartridges.

PMID- 15461386
TI  - Immuno-quantitative polymerase chain reaction for detection and quantitation of
      prion protein.
AB  - Immuno-polymerase chain reaction (PCR) is an extremely sensitive detection
      method, combining the specificity of antibody detection and the sensitivity of
      PCR. We have developed an immuno-quantitative PCR (iqPCR), exploiting real-time
      PCR technology, in order to improve this immuno-detection method and make it
      quantitative. To illustrate the advantages of iqPCR, we have compared it with a
      conventional enzyme linked immuno sorbent assay (ELISA) technique in experiments
      aimed at detecting the cellular and the resistant form of prion protein in bovine
      brain extract. The iqPCR technique proved to be more sensitive than ELISA, so it
      could be a technique of choice for the diagnosis of infected animals both at an
      ante mortem and post-mortem stage.

PMID- 15461387
TI  - Statistical correction for non-parallelism in a urinary enzyme immunoassay.
AB  - Our aim was to develop a statistical method to correct for non-parallelism in an
      estrone-3-glucuronide (E1G) enzyme immunoassay (EIA). Non-parallelism of serially
      diluted urine specimens with a calibration curve was demonstrated in an EIA for
      E1G. A linear mixed-effects analysis of 40 urine specimens was used to model the
      relationship of E1G concentration with urine volume and derive a statistical
      correction. The model was validated on an independent sample and applied to 30
      menstrual cycles from American women. Specificity, detection limit, parallelism,
      recovery, correlation with serum estradiol, and imprecision of the assay were
      determined. Intra-and inter-assay CVs were less than 14% for high- and low-urine
      controls. Urinary E1G across the menstrual cycle was highly correlated with serum
      estradiol (r= 0.94). Non-parallelism produced decreasing E1G concentration with
      increase in urine volume (slope = -0.210, p < 0.0001). At 50% inhibition, the
      assay had 100% cross-reactivity with E1G and 83% with 17beta-estradiol 3
      glucuronide. The dose-response curve of the latter did not parallel that of E1G
      and is a possible cause of the non-parallelism. The statistical correction
      adjusting E1G concentration to a standardized urine volume produced parallelism
      in 24 independent specimens (slope = -0.043+/-0.010), and improved the average CV
      of E1G concentration across dilutions from 19.5%+/-5.6% before correction to
      10.3%+/-5.3% after correction. A statistical method based on linear mixed effects
      modeling is an expedient approach for correction of non-parallelism, particularly
      for hormone data that will be analyzed in aggregate.

PMID- 15461388
TI  - Development of liposome immune lysis assay for the herbicide atrazine.
AB  - A homogeneous complement-mediated liposome immune lysis assay (LILA) was
      developed for determination of the herbicide atrazine. To dispose the antigen on
      the surface of lipid bilayer the atrazine was conjugated to a
      dimirystoylphosphatidylethanolamine (DMPE) carrier. Calcein was compared with
      sulforhodamine 101 as a fluorophore label for entrapping into the antigen
      sensitized liposomes. The liposomes were incubated with rabbit anti-atrazine
      antibodies in the presence of guinea pig complement. Formation of the antigen
      antibody complexes on the liposomal surface initiated the lytic action of the
      complement. As free competing atrazine inhibited the lytic reaction, the amount
      of calcein released was inversely proportional to the atrazine content in the
      probe. Concentration and kinetic dependences of the immunoassay were
      characterized to reach its maximal sensitivity. The developed assay allows
      detecting atrazine in concentrations up to 0.13 ng mL(-1) in the sample (0.04 ng
      mL(-1) in the final reaction mixture). The named sensitivity is two orders higher
      than those for the microplate enzyme-linked immunosorbent assay (ELISA) with the
      same antibodies which allows us to recommend LILA for environmental monitoring.

PMID- 15461389
TI  - Carbodiimide or periodate method to prepare peroxidase hydrazide for its use in
      immunoassay.
AB  - Peroxidase hydrazides were prepared by conjugating horseradish peroxidase (HRP)
      to adipic acid dihydrazide (ADH) by carbodiimide or periodate oxidation method.
      The resulting HRP hydrazides (ADH-HRP) were conjugated to cortisol-21
      hemisuccinate (cortisol-21-HS) by forming diimide bonds using the N
      hydroxysuccinimide (NHS) carbodiimide mediated reaction. The prepared cortisol-21
      HS-ADH-HRP enzyme conjugates were utilized for the development of an enzyme
      linked immunosorbent assay (ELISA) for direct estimation of cortisol. To the
      cortisol antibody coated microtiter wells, standard or serum sample (50 microL),
      along with 100 microL of cortisol-21-HS-ADH-HRP enzyme conjugate (ADH-HRP used is
      prepared by either carbodiimide or periodate oxidation method), was incubated for
      1 hr at 37 degrees C. Bound enzyme activity was measured by using tetramethyl
      benzidine/hydrogen peroxide (TMB/H202) as substrate. The sensitivity,
      specificity, and recovery of the assays were found to be identical when ELISAs
      were employed with cortisol enzyme conjugates prepared by conjugating cortisol-21
      HS to HRP hydrazide, made either by the carbodiimide method or periodate
      oxidation method.

PMID- 15461390
TI  - Outbreak news.

PMID- 15461391
TI  - Special campaigns to eliminate leprosy: improving services.

PMID- 15461392
TI  - "A good education is ...." The development of evaluative thought across the life
      span.
AB  - The author uses a cognitive developmental approach to investigate educational
      conceptions, addressing the question, How does evaluative reasoning about
      education change over the course of cognitive development? The author conducted
      independent analyses of the developmental level and conceptual content of 246
      interview performances of individuals aged 5 to 86 years. The developmental level
      of the interview performances was assessed with a content-general scoring system,
      the Hierarchical Complexity Scoring System. A Rasch analysis of the results
      revealed 6 developmental levels and provided support for invariant sequence,
      developmental spurts and plateaus, and similar developmental patterns for
      childhood and adulthood levels. The results of the subsequent analysis of the
      propositional content of the same interview texts were used to produce
      qualitative descriptions of changes in evaluative reasoning about education
      across the 6 levels identified in the data. Finally, descriptions constructed in
      this way, although richer and less prone to reification, were shown to be
      conceptually analogous to the stage definitions produced by other cognitive
      developmental researchers. The implications of the method and findings are
      discussed.

PMID- 15461393
TI  - Modelling carbon oxidation in pulp mill activated sludge systems: calibration of
      Activated Sludge Model No 3.
AB  - Activated Sludge Model No 3 (ASM3) was chosen to model an activated sludge system
      treating effluents from a mechanical pulp and paper mill. The high COD
      concentration and the high content of readily biodegradable substrates of the
      wastewater make this model appropriate for this system. ASM3 was calibrated based
      on batch respirometric tests using fresh wastewater and sludge from the treatment
      plant, and on analytical measurements of COD, TSS and VSS. The model, developed
      for municipal wastewater, was found suitable for fitting a variety of
      respirometric batch tests, performed at different temperatures and food to
      microorganism ratios (F/M). Therefore, a set of calibrated parameters, as well as
      the wastewater COD fractions, was estimated for this industrial wastewater. The
      majority of the calibrated parameters were in the range of those found in the
      literature.

PMID- 15461394
TI  - Multi-component kinetics of activated sludge treatment of bleached kraft mill
      effluent.
AB  - This study investigated the discrepancies between the BOD removal rates measured
      during short term assays and those measured during continuous activated sludge
      treatment of bleached kraft mill effluent (BKME). A combination of batch tests
      and fed batch tests with oxygen uptake rate (OUR), chemical oxygen demand (COD),
      biochemical oxygen demand (BOD), and mixed liquor volatile suspended solids
      (MLVSS) measurements were used to characterize the degradation rates for the
      activated sludge treatment of BKME and to divide the soluble readily
      biodegradable substrate into two to five separate fractions based on
      biodegradation rates. The removal rates varied by over an order of magnitude
      between the most readily degradable substrates (1 x 10(-3) mg COD/mg MLVSS
      minute), and the more slowly degradable substrates (2 x 10(-5) mg COD/mg MLVSS
      minute). If the readily biodegradable fraction of BKME was modeled as one
      substrate, initial rate kinetic measurements from batch tests were heavily
      influenced by the fractions with the greatest degradation rates, while any
      remaining BOD in the treated effluent was predominantly from the slowly
      degradable fraction, giving inconsistent results. Taking the multi-component
      nature of the wastewater into account, batch test results can be used to predict
      fed-batch and continuous activated sludge reactor performance.

PMID- 15461395
TI  - The fate of metals in forest industry wastewater treatment systems.
AB  - The capture/removal of a range of metals was estimated for a number of pulp and
      paper wastewater treatment systems. Both long-term wastewater data and
      accumulated sludge data were examined. Only copper and lead were effectively
      captured (greater than 50%) by all sites and estimate methods. Zinc capture
      exceeded 50% in all but one case. Qualitatively, iron, aluminium, cadmium, and
      cobalt were usually captured to a significant extent. The sludge inventory-based
      approach and the wastewater system inlet-outlet approach gave reasonably similar
      capture estimates.

PMID- 15461396
TI  - Occurrence and control of filamentous bulking in aerated wastewater treatment
      plants of the French paper industry.
AB  - The occurrence of filamentous bacteria was investigated in 15 French pulp and
      paper activated sludge wastewater treatment plant (WWTP). Large filamentous
      populations were present in most of the plants. Identification carried out with
      conventional methods based on morphological features and staining techniques
      showed that the four main filamentous bacteria encountered in these industrial
      WWTP and responsible for bulking belong to the genera Thiothrix sp., Type 021 N,
      Haliscomenobacter hydrossis and Type 0092. During two years a specific survey was
      performed for three of these WWTP showing recurrent bulking phenomena. Data from
      WWTP performance, chemical data and filaments characterization were compared to
      correlate the presence of specific filaments with process operating conditions.

PMID- 15461397
TI  - Occurrence and significance of filamentous bacteria in pulp and paper activated
      sludge systems.
AB  - A microbial survey of 27 activated sludge (AS) systems included 16 conventional
      activated sludge (CAS) systems, five sequential batch reactors (SBR) and six
      oxygen-activated sludge (OAS) systems, all treating pulp and paper effluents. The
      most prevalent filaments observed were Thiothrix (26%) and Type 021N (22%). The
      designs of the activated sludge systems seemed to have an effect on the filament
      types. We found Thiothrix to be the most common filament associated with bulking.
      For CAS systems, a completely mixed mode of operation promoted Thiothrix and Type
      021N growth. Type 021N was favoured in CAS systems with food to microorganism
      (F/M) ratios higher than 0.2, and with dissolved oxygen (DO) residuals higher
      than 2 ppm, while Thiothrix generally proliferated at lower F/M ratio and DO
      residuals. Nutrient deficiencies as well as nutrient dosage variations were
      suspected in most of the systems having Thiothrix and Type 021N as the most
      prevalent filaments. Thiothrix appeared to prefer polyphosphate and/or ammonia
      rather than urea/phosphoric acid as N and P sources. Systems with aerobic
      selectors showed the lowest filament counts, while systems with no selectors
      showed the highest filament counts.

PMID- 15461398
TI  - Common stresses affecting activated sludge health and performance--what the four
      assay set can tell us.
AB  - Previously, we developed a novel biological early warning (BEW) system for
      directly monitoring the health and performance of activated sludge, the "four
      assay set". In the present work, the four-assay set has been used to measure the
      effects of four common stresses on activated sludge biomass: high temperature;
      pH; anoxia; and starvation. The results demonstrate both the utility of the
      Paprican four-assay set as a biomass-evaluating and BEW tool, and the tolerances
      of a typical kraft mill activated sludge for these four stresses.

PMID- 15461399
TI  - Organic matter balance in ECF kraft mill fiberline.
AB  - Organic matter balances of an ECF kraft mill fiberline were studied in three
      different operational conditions of the oxygen delignification stage by
      implementing mill measurements, collecting routine mill data and combining them
      in a modified PROCELL steady state model. Dissolved volatile solids was the basic
      measurement for organic matter in liquid streams. Normal operation of the
      O2D0E(O)D1E(OP)D2 fiberline was described successfully. It was also possible to
      describe exceptional operating situations in the oxygen delignification stage and
      their effects on other parts of the production process reasonably well in order
      to focus studies on aspects requiring further attention. The existence of organic
      matter lost through complete degradation and volatile organic compounds in unit
      processes as well as its sensitivity to yield and operational situations is
      shown. The different perspectives of pulp production and wastewater treatment can
      be brought closer to each other using the approach in this study. The variation
      in the fractions discharged to wastewater treatment, although a relatively small
      share of the overall organic matter balance, will continue to become more
      important also for pulp production when effluent streams are increasingly turned
      back to the production line through further closure. Studies like the one
      presented here, can contribute to the evaluation of this development.

PMID- 15461400
TI  - The assessment of different operating strategies for minimising activated sludge
      deflocculation under temperature transient conditions.
AB  - Three operating strategies were tested for decreasing activated sludge
      deflocculation due to temperature shifts from 30 degrees to 45 degrees C:
      magnesium sludge enrichment, increased sludge retention time (33 d), and spikes
      of an easily degradable substrate (methanol). The temperature shifts were
      conducted sequentially in 4 parallel lab-scale sequencing batch reactors (SBRs)
      treating kraft pulp mill effluent. Three SBRs operated at an SRT = 20 days, and
      in one of them the sludge was not manipulated, thus, serving as a reference SBR.
      The temperature shift was associated with decreased soluble chemical oxygen
      demand (SCOD) removals, decreased sludge settleability and substrate removal
      capacity, and increased effluent suspended solids (ESS) and turbidity levels. The
      shift also increased the sludge specific respiration rates and reduced the sludge
      substrate removal capacity. Sludge deflocculation was assessed as floc
      solubilisation (increased effluent SCOD levels) and floc fragmentation (increase
      in effluent solids smaller than 50 microm). Mg enrichment of the sludge and
      methanol spikes reduced the ESS levels (in 9 and 25%), and the three operating
      strategies decreased effluent turbidity (in 22-35%) compared to the maximum
      levels from the non-manipulated reactor (44 mg ESS/L). The stronger sludge floc
      structure achieved by magnesium enrichment and a high sludge age of 33 days was
      unsuccessful in significantly decreasing deflocculation. The mechanisms involved
      in sludge deflocculation require further fundamental research.

PMID- 15461401
TI  - Evaluation of total phosphorus and total nitrogen methods in pulp mill effluents.
AB  - Under the Clean Water Action Plan, the US Environmental Protection Agency is
      requiring states to establish numeric criteria for phosphorus and nitrogen. In
      preparation for the development of nutrient criteria NCASI undertook a research
      project to conduct a comparative study of methods for the determination of total
      phosphorus and total nitrogen in pulp and paper mill matrices. This paper
      presents results of a single laboratory method evaluation and comparative study
      of digestion techniques and analytical methods for the determination of total
      phosphorus (TP) and total nitrogen (TN) in pulp and paper mill secondary treated
      effluents. Analytical methods included EPA Methods 365.2 and 365.4 for TP. TN and
      total kjeldahl nitrogen (TKN) methods included EPA Methods 351.2, 351.4, and
      353.2. Examinations of sample preservation and storage stability were conducted.
      Substitution of mercuric sulfate with copper sulfate during block digestion
      resulted in higher blank levels and method detection limits. TP measurements
      using EPA Method 365.4 (autoanalyzer) were found to be accurate with a positive
      bias as determined using matrix spike experiments. Sample digestion by acidic
      persulfate oxidation or mercuric sulfate block digestion in conjunction with EPA
      Method 365.4 yielded low blank levels (averages of 0.01 and 0.02 mg/L,
      respectively), precision of 2.1 and 2.4% relative standard deviations,
      respectively, and accuracy expressed as an average recovery (%R) of 117% for
      both. EPA Method 351.2 (autoanalyzer) was more precise than EPA Method 351.4
      (ammonia probe). Accuracy (%R) for EPA Method 351.2 ranged from 81 to 95%,
      depending on the digestion technique applied, and was 55% when EPA Method 351.4
      was utilized. Investigation of a method utilizing basic to acidic persulfate
      oxidation for the simultaneous determination of TN and TP using only two
      analytical techniques was found to be effective at concentrations above 1 mg/L in
      pulp mill effluents.

PMID- 15461402
TI  - The formation of colour during biological treatment of pulp and paper wastewater.
AB  - Colour discharges are gaining renewed focus in the pulp and paper industry as
      increasingly strict regulatory limits are placed on wastewater quality and
      aesthetics. In-mill process improvements, such as ECF bleaching and oxygen
      delignification, have decreased wastewater colour loadings. However, a survey of
      12 pulp and paper mill systems found that effluent treatment using aerated
      stabilisation basins (ASB) leads to average increases in colour of 20-40%. In
      some instances, this phenomenon may even double the influent colour levels.
      Activated sludge systems did not produce a colour increase. The measured
      increases that follow ASB secondary treatment may be sufficient for a mill to
      fail prescribed discharge standards. A detailed field survey focusing on sections
      of an integrated bleached kraft mill ASB treatment system was undertaken. The
      average increase in colour at the final point of discharge was 45%. The major
      changes in colour concentration occurred in the inlet to the main treatment pond,
      and in polishing ponds that followed the main treatment pond. Both of these areas
      receive little or no aeration. No significant change was observed in the highly
      aerated main pond. These results, along with literature reports, suggested that
      redox conditions play a major role in influencing colour behaviour. To test this,
      two series of paired continuously stirred reactors were used to treat whole mill
      effluent from two ECF bleached kraft mills in parallel. The first series
      initially treated under anaerobic conditions, followed by an aerobic reactor,
      while the second series reversed this order. With the initial anaerobic stage,
      effluent colour increased by 18% and 19% for the first and second series
      respectively. Subsequent treatment by aerobic bacteria further increased colour
      by 14% and 6%, for a total increase of 32% and 25%. Initial aerobic treatment,
      however, did not lead to any significant change in colour for either effluent.
      Further anaerobic treatment following aerobic conditions produced only small
      increases in colour. These results are consistent with the ASB and activated
      sludge system survey, suggesting that anaerobic conditions at the head of
      treatment systems initiate the observed increases in effluent colour in ASB
      treatment systems.

PMID- 15461403
TI  - Pilot-scale comparison of thermophilic aerobic suspended carrier biofilm process
      and activated sludge process in pulp and paper mill effluent treatment.
AB  - Thermophilic aerobic treatment of settled pulp and paper mill effluent was
      studied under mill premises with two comparative pilot processes; suspended
      carrier biofilm process (SCBP) and activated sludge process (ASP). Full-scale
      mesophilic activated sludge process was a reference treatment. During the runs
      (61 days) hydraulic retention times (HRTs) were kept 13+/-5 h and 16+/-6 h for
      SCBP and ASP, respectively. Corresponding volumetric loadings rates (VLR) were
      2.7+/-0.9 and 2.2+/-1.0 kg CODfilt m(-3)d(-1). Temperatures varied between 46 to
      60 degrees C in both processes. Mesophilic ASP was operated with HRT of 36 h,
      corresponding VLR of 0.7 kg CODfilt m(-3)d(-1). Both SCBP and ASP achieved
      CODfilt (GF/A filtered) removals up to 85%, while the mesophilic ASP removal was
      89+/-2%. NTU values were markedly higher (100-300) in thermophilic effluents than
      in mesophilic effluent (30). Effluent turbidity was highly dependent on
      temperature; in batch experiment mesophilic effluent sample had NTU values of 30
      and 60 at 35 degrees C and 55 degrees C, respectively. As a conclusion, both
      thermophilic treatments gave high CODfilt removals, which were close to
      mesophilic process removal and were achieved with less than half of HRT.

PMID- 15461404
TI  - A comparison of conventional activated sludge and low sludge production
      strategies for advanced treatment of kraft pulp mill effluent.
AB  - Parallel laboratory investigations were conducted to examine aspects of two
      distinct but related bioprocess strategies for low sludge production in the
      treatment of the same TCF kraft pulp mill effluent. The purpose of this article
      has been to compare the performance results from these two bench-scale trials
      with respect to nutrient demands, nutrient discharge, COD removal, and waste
      sludge characteristics. The LSP (Low Sludge Production) process can be used to
      significantly reduce sludge yield with excellent sludge characteristics. These
      sludge characteristics seemed to be related to elevated protozoan grazing
      pressures. The BAS (Biofilm-Activated Sludge) process achieves similar reduced
      sludge yields and sludge characteristics while at the same time significantly
      reducing the nutrient demands and discharge levels. For both LSP and BAS process
      optimization, the selector nutrient loading is critical to the overall process
      performance. Selector nutrient requirements are distinct from the overall process
      nutrient requirements.

PMID- 15461405
TI  - Nutrient minimisation in the pulp and paper industry: an overview.
AB  - This paper reviews nutrient issues within the pulp and paper industry
      summarising: nitrogen and phosphorus cycles within treatment systems; sources of
      nutrients within pulping and papermaking processes; minimising nutrient
      discharge; new approaches to nutrient minimisation; and the impact of nutrients
      in the environment. Pulp and paper industry wastewaters generally contain
      insufficient nitrogen and phosphorus to satisfy bacterial growth requirements.
      Nutrient limitation has been linked to operational problems such as sludge
      bulking and poor solids separation. Nutrients have been added in conventional
      wastewater treatment processes to ensure optimum treatment performance.
      Minimising the discharge of total nitrogen and phosphorus from a nutrient limited
      wastewater requires both optimised nutrient supplementation and effective removal
      of suspended solids from the treated wastewater. In an efficiently operated
      wastewater treatment system, the majority of the discharged nutrients are
      contained within the biomass. Effective solids separation then becomes the
      controlling step, and optimisation of secondary clarification is crucial.
      Conventional practice is being challenged by the regulatory requirement to reduce
      nitrogen and phosphorus discharge. Two recent developments in pulp and paper
      wastewater treatment technologies can produce discharges low in nitrogen and
      phosphorus whilst operating under conventionally nutrient limited conditions: i)
      the nutrient limited BAS process (Biofilm-Activated Sludge) which combines
      biofilm and activated sludge technologies under nutrient limited conditions and
      ii) an activated sludge process based on the use of nitrogen-fixing bacteria.
      Aerated stabilisation basins often operate without nutrient addition, relying on
      settled biomass in the benthal zone feeding back soluble nutrients, or the
      fixation of atmospheric nitrogen. Thus effective nutrient minimisation strategies
      require a more detailed understanding of nutrient cycling and utilisation. Where
      it is not possible to meet discharge constraints with biological treatment alone,
      a tertiary treatment step may be required. In setting nutrient control
      guidelines, consideration should be given to the nutrient limitations of the
      receiving environment, including other cumulative nutrient impacts on that
      environment. Whether an ecosystem is N or P limited should be integrated with
      wastewater treatment considerations in the further design and development of
      treatment technology and regulatory guidelines. End-of-pipe legislation alone
      cannot predict environmental effects related to nutrients and must be
      supplemented by an effects-based approach.

PMID- 15461406
TI  - Full scale implementation of the nutrient limited BAS process at Sodra Cell Varo.
AB  - A combination of the suspended carrier biofilm process and the activated sludge
      process (biofilm-activated sludge--BAS) has been shown to be very successful for
      the treatment of different types of pulp and paper mill effluents. The robust
      biofilm pre-treatment in combination with activated sludge results in a stable,
      compact and highly efficient process. Recent findings have shown that nutrient
      limited operation of the biofilm process greatly improves the sludge
      characteristics in the following activated sludge stage, while minimising sludge
      production and effluent discharge of nutrients. The nutrient limited BAS process
      was implemented at full scale at the Sodra Cell Varo kraft mill and taken into
      operation in July 2002. After start-up and optimisation over about 5 months, the
      process meets all effluent discharge limits. The removal of COD is close to 70%
      and the removal of EDTA greater than 90%. Typical effluent concentrations of
      suspended solids and nutrients during stable operations have been 20-30 mg/L TSS,
      0.3-0.5 mg/L phosphorus and 3-5 mg/L nitrogen. The sludge production was 0.09
      kgSS/kg COD removed and the sludge volume index was 50-100 mL/g.

PMID- 15461407
TI  - N-ViroTech--a novel process for the treatment of nutrient limited wastewaters.
AB  - As pulp and paper wastewaters are mostly deficient in nitrogen and phosphorus,
      historical practice has dictated that they cannot be effectively treated using
      microbiological processes without the addition of supplementary nutrients, such
      as urea and phosphoric acid. Supplementation is a difficult step to manage
      efficiently, requiring extensive post-treatment monitoring and some degree of
      overdosing to ensure sufficient nutrient availability under all conditions. As a
      result, treated wastewaters usually contain excess amounts of both nutrients,
      leading to potential impacts on the receiving waters such as eutrophication. N
      ViroTech is a highly effective alternative treatment technology which overcomes
      this nutrient deficiency/excess paradox. The process relies on communities of
      nitrogen-fixing bacteria, which are able to directly fix nitrogen from the
      atmosphere, thus satisfying their cellular nitrogen requirements. The process
      relies on manipulation of growth conditions within the biological system to
      maintain a nitrogen-fixing population whilst achieving target wastewater
      treatment performance. The technology has significant advantages over
      conventional activated sludge operation, including: Improved environmental
      performance. Nutrient loadings in the final treated effluent for selected
      nitrogen and phosphorus species (particularly ammonium and orthophosphate) may be
      reduced by over 90% compared to conventional systems; Elimination of nitrogen
      supplementation, and minimisation of phosphorus supplementation, thus achieving
      significant chemical savings and resulting in between 25% and 35% savings in
      operational costs for a typical system; Self-regulation of nutrient requirements,
      as the bacteria only use as much nitrogen as they require, allowing for
      substantially less operator intervention and monitoring. This paper will
      summarise critical performance outcomes of the N-ViroTech process utilising
      results from laboratory-, pilot-scale and recent alpha-adopter, full-scale
      trials.

PMID- 15461408
TI  - Degradation of EDTA and DTPA in chlorine dioxide bleaching conditions.
AB  - The decomposition of EDTA and DTPA was studied in simulated chlorine dioxide
      bleaching conditions. Under the investigated conditions EDTA and DTPA decomposed
      readily. Accordingly, feeding the chelating agents to the first chlorine dioxide
      stages (D0) should be reconsidered, when successful metal removal is desired. On
      the other hand, chlorine dioxide water may be utilized to degrade the chelating
      agents.

PMID- 15461409
TI  - Integrated biological treatment of recalcitrant effluents from pulp mills.
AB  - This work aimed at determining the degree of depuration of a recalcitrant
      effluent (weak black liquor, WBL) achieved in a series treatment consisting of a
      first stage methanogenic fluidised bed reactor followed by a second stage
      aerobic, upflow reactor packed with "biocubes" of Trametes versicolor immobilised
      onto small cubes of holm oak wood. The mesophilic, lab scale methanogenic
      fluidised bed reactor contained a microbial consortium immobilised onto granular
      activated carbon 500 microm average size. The process removed decreasing amounts
      of organic matter at decreasing hydraulic retention times (HRT), eventually
      reaching an average of 50% at 0.5 day HRT. Colour and ligninoid removals also
      decreased with decreasing HRT. Although the methanogenic fluidised bed reactor
      provided an effective treatment for the degradable organic matter, important
      concentrations of recalcitrant organic matter and colour still remained in the
      anaerobic effluent. This anaerobic effluent was fed to the aerobic packed bed
      reactor. Two HRT were tested in this unit, namely 5 and 2.5 days. The reactor
      averaged an organic matter removal in the range of 32% COD basis, during an
      experimental run of 95 days. Colour and ligninoid contents were removed in high
      percentages (69% and 54%, respectively). There was no significant difference in
      reactor performance at 5- and 2.5-day HRT. There was a positive correlation
      between pollutant removal efficiencies and Laccase activity in crude extracts of
      the reactor liquor. No supplemental soluble carbohydrate was required to sustain
      the fungus activity and the consistent reactor performance. Overall, the two
      stage treatment achieved approximately a 78% removal of the original organic
      matter of the WBL (COD basis) and ca. 75% of colour and ligninoid contents.

PMID- 15461410
TI  - Spectroscopic evidence of silica-lignin complexes: implications for treatment of
      non-wood pulp wastewater.
AB  - This research examined the hypothesis that lignin compounds form aqueous
      complexes with silica increasing its solubility, thereby inhibiting its
      precipitation. An experimental program using four lignin model compounds was
      conducted to test the hypothesis. Laser Raman spectroscopy (LRS) was used to
      characterize, qualitatively, the interaction between lignin and aqueous silica,
      and to identify the possibility of silica-lignin complexation. Solubility studies
      were then performed by analyzing the solubility of silica in presence and absence
      of lignin within the relevant pH range to confirm the results of LRS, and to
      obtain a quantitative assessment of the relative solubility. The findings have
      established the formation of silica-ferulic, silica-vanillic, and silica-4
      methoxycinnamic acid complexes, but no evidence was detected for the formation of
      silica-veratryl alcohol complex. In fact, the black liquor undoubtedly contains
      much more complex lignin materials than the simple model compounds used in this
      work. The more complex lignin compounds are likely to have an even greater
      tendency to form silica complexes, thus contributing to the initial hypothesis.
      This finding provides a fundamental understanding as to why previous efforts to
      precipitate silica by lowering the pH from 10-11 (for black liquor) to less than
      9 did not achieve satisfactory silica separation, and why alternative strategies
      need to be investigated.

PMID- 15461411
TI  - Ozonolysis mechanism of lignin model compounds and microbial treatment of organic
      acids produced.
AB  - Treatment methods comprising ozonolysis and microbial treatment of lignin
      discharged from the pulp manufacture industries were investigated by using a
      sulfite pulp wastewater and a lignin model compound, i.e. sodium lignosulfonate.
      Dynamic behaviors for the formations of intermediate derivatives such as muconic
      acid, maleic acid, and oxalic acid produced from the ozonolysis of sulfite pulp
      wastewater were observed from data of UV absorption at 280 nm by a
      spectrophotometer and at 210 nm by high performance liquid chromatography. The
      microorganisms that were isolated by the enrichment culture method were used to
      degrade the organic acids such as oxalic acid and acetic acid. Time courses of
      biological degradation of these organic acids indicated diauxic growth, which was
      found in a culture with mixed substrates. In the treatment of sodium
      lignosulfonate, the ozonolysis and microbial treatment using activated sludge
      converted sodium lignosulfonate into carbon dioxide and water almost completely.

PMID- 15461412
TI  - Using ozone to reduce recalcitrant compounds and to enhance biodegradability of
      pulp and paper effluents.
AB  - The effect of ozone based oxidation on removing recalcitrant organic matter (ROM)
      and enhancing the biodegradability of alkaline bleach plant effluent was
      investigated. A bubble column ozonation tower was used in the study. The
      experiments were carried out at different temperatures (20 degrees C and 60
      degrees C) and pH (9 and 11), with a number of biological and chemical parameters
      being monitored including BOD5, COD, TC, pH, color, and molecular weight
      distribution of organics (nominal cut off of 1,000 Da). Biodegradability of the
      effluent was determined based on BOD5/COD of the wastewater throughout the
      process. For all the experiments, ozonation enhanced the biodegradability of the
      effluent by 30-40%, which was associated with noticeable removal of ROM including
      high molecular weight (HMW) and color-causing organics by about 30% and 60%,
      respectively. While the biodegradability of HMW fraction increased by about 50%,
      there was no biodegradability improvement for low molecular weight (LMW) portion,
      which was originally readily biodegradable (with BOD5/COD of about 0.5).
      Statistical analysis of variance (ANOVA) revealed neither pH nor temperature
      played significant role on the ozonation process at 95% confidence level.

PMID- 15461413
TI  - Pulp mill process closure: a review of global technology developments and mill
      experiences in the 1990s.
AB  - The impact of effluent discharges continues to be an important issue for the pulp
      manufacturing industry. Considerable progress has been made in pollution
      prevention to minimize waste generation, so-called manufacturing "process
      closure." Since the mid-1980s many important technologies have been developed and
      implemented, many of these in response to organochlorine concerns. Zero effluent
      operation is now a reality for a few bleached chemi-thermomechanical pulp (BCTMP)
      pulp mills. In kraft pulp manufacturing, important developments include
      widespread adoption of new cooking techniques, oxygen delignification, closed
      screening, improved process control, new bleaching methods, and systems that
      minimize pulping liquor losses. Coupled to this is a commitment to reduce water
      use and maximize reuse of in-mill process streams. Some companies pursued bleach
      plant closure, and many have been successful in eliminating a portion of their
      bleaching wastewaters. However, the difficulties inherent in closing bleach
      plants are considerable. For many mills the optimal solution has been found to be
      a high degree of closure coupled with external biological treatment of the
      remaining process effluent. No bleach plants at papergrade bleached kraft mills
      are known to be operating effluent-free on a continuous basis. This paper reviews
      the important worldwide technological developments and mill experiences in the
      1990s that were focused on minimizing environmental impacts of pulp manufacturing
      operations.

PMID- 15461414
TI  - Biological treatment of whitewater in a laboratory process in order to determine
      kinetic parameters for model development.
AB  - Implementation of an in-mill biological treatment plant is one solution to the
      problems associated with closure of whitewater systems. It is, however, important
      to operate the treatment with low concentration of nutrients in the effluent. The
      effect on the COD reduction from decreased additions of NH4-N and PO4-P were
      investigated in three parallel aerobic suspended carrier reactors during
      treatment at 46 to 48 degrees C of whitewater from a recycled paper mill
      producing liner and fluting. In the reference reactor, a COD reduction of 89% was
      achieved and 45.6 mg NH4-N/(g COD reduced) and 11.6 mg PO4-P/(g COD reduced) was
      consumed at an organic load around 20 kg COD/(m3 x d). Reduced additions of NH4-N
      decreased the COD reduction. Addition of 56% of the consumption of NH4-N in the
      reference reactor resulted in a COD reduction of 80%. The response from decreased
      addition of PO4-P was different compared to NH4-N but it could not be determined
      if this is due to unsuitable experimental design or a different reaction
      mechanism. Reducing the addition of PO4-P to 26% of the consumption of PO4-P in
      the reference reactor, decreased the COD reduction to 83%. The main conclusion
      from the experiment is: biological treatment has the potential of treating
      whitewater from recycled paper mills with low effluent nutrient concentrations.

PMID- 15461415
TI  - New method for measuring potential secondary stickies in deinked pulp filtrates.
AB  - Secondary stickies refer to sticky material in recycled fiber process streams,
      which has been dissolved in one part of process, but turned to solid phase due to
      changes in process conditions. The material that can later form secondary
      stickies is called potential secondary stickies. A new, fast, and simple method
      for measuring the amount of potential secondary stickies was developed to measure
      the purification result in the deinked pulp (DIP) filtrates. The new method, now
      called potential secondary stickies method, was tested with process waters from a
      recycled fiber (RCF) plant. The method was found to be reliable. Several
      chemicals and chemical combinations were tested in laboratory scale and compared
      as coagulation-flocculation agents in two dissolved air flotations (DAF) used as
      internal water treatment units at the RCF plant. With potential secondary
      stickies method, significant differences between the effectiveness of the
      chemicals were found, whereas no difference was seen in the quality of purified
      process water with traditional measuring methods. The measurement method was also
      used in mill during a two-week measuring period. As a conclusion, it can be said
      that this method can be used to monitor the quality and to predict the changes in
      DIP process water.

PMID- 15461416
TI  - Water circuit closure with membrane technology in the pulp and paper industry.
AB  - In this study, membrane filtration as an internal purification method, "the
      kidney", in the pulp and paper industry is discussed. Membrane filtration is
      economically competitive and a very versatile process. It can be used to remove
      the enriched organic and/or inorganic loads either partially or totally from, for
      example, the mechanical pulping and paper making water circuits and it can be
      applied to various points within the process. With the so-called shear enhanced
      membrane modules very high fluxes, in ultrafiltration about 400 L/(m2h) and in
      nanofiltration fluxes almost 200 L/(m2h), have been obtained. Depending on the
      membrane, suspended solids (microfiltration), polysaccharides, extractives and
      high molar mass lignous substances (ultrafiltration) and multivalent salts
      (nanofiltration) can be removed. Ultrafiltration permeate can well be used in
      paper machine showers to replace fresh water. The quality of the nanofiltration
      permeate is significantly higher than that of ultrafiltration. The membrane
      processes can be enhanced by various pre-treatment techniques to produce higher
      permeate fluxes and to eliminate membrane fouling. Such pre-treatment methods
      are, e.g., chemical treatment, ozonation and biological treatment. The most cost
      effective processes were chemical flocculation, pH adjustment and thermophilic
      aerobic biological treatment.

PMID- 15461417
TI  - Ultrafiltration and nanofiltration in the pulp and paper industry using cross
      rotational (CR) filters.
AB  - Ultra- and nanofiltration with high shear CR-filters have been utilized for
      cleaning of clear filtrates and effluents from the pulp and paper industry. The
      aim was to find out how different nanofiltration membranes operate at high shear
      conditions. The filtration efficiency of the membranes was evaluated by measuring
      flux, retention and fouling at various recovery and pH conditions. High fluxes
      (approximately 100 L/(m2h)) for nanofiltration membranes were measured when
      circulation waters from the paper machine were filtered at neutral conditions. In
      the filtration of discharge of external activated sludge treatment plants we
      measured fluxes around 150 L/(m2h) even at a concentration factor of 12. The best
      NF membranes removed over 80% of the organic carbon and of the conductivity and
      almost completely eliminated the color. With acidic waters fluxes and retentions
      were significantly lower. The NF270 membrane from Dow and the Desal-5 membranes
      from Osmonics had the highest flux and retention properties. However, the Desal-5
      membrane lost its retention properties slowly, which restricts its use in the
      high shear CR-filter. CR-nanofiltration can be used in the pulp and paper
      industry without feed pre-treatment by ultrafiltration. This increases the
      attractiveness of high shear CR-nanofiltration.

PMID- 15461418
TI  - Investigation of heavy metals transportation from soil to the pine tree.
AB  - The Scots pine (Pinus sylvestris L.) is the most common tree in Lithuanian
      forests. Research on the impact of pollutants on pines allows us to evaluate
      pollutants in a major part of Lithuanian forests. Heavy metals (HMs) are among
      the major pollutants entering forest ecosystems in different ways: in their wet
      and dry form they come from local or distant sources of emission by being
      transported from seas alongside with nutrients and sea salt, washed up from the
      dead plants accumulated in soil, and together with mineral particles brought by
      wind or water. During the period of investigation, a decrease in the Cr
      concentration in pine rings is seen. High Zn concentrations (in 1987--1989 Zn
      concentration was 27.6 mg x kg(-1)) in the pine may be caused by emissions from
      heavy traffic. The results have shown that Mn has the highest concentration as
      compared with that of other HMs in the soil around the pine (at the depth of 30
      40 cm, Mn concentration is 780 mg x kg(-1)). In comparison with other HMs, Cu and
      Zn have the largest factor of transport from the soil to the wood (0.39 and 0.49
      respectively).

PMID- 15461419
TI  - Advanced treatment by anaerobic process followed by aerobic membrane bioreactor
      for effluent reuse in paper mill industry.
AB  - The operation of an activated sludge process at a paper mill (AIPM) in Hedera,
      Israel, was often characterized by disturbances. As part of a research and
      development project, a study on new biological treatment was initiated. The study
      included the operation of three pilot units: a. anaerobic treatment by upflow
      anaerobic sludge blanket (UASB); b. aerobic treatment by two pilot units
      including activated sludge and membrane bioreactor (MBR), which have been
      operated in parallel for comparison reasons. The pilot plant working on anaerobic
      treatment performed COD reduction from 2,365 to 755 mg/L, expressed as average
      values. Based on the pilot study, a full scale anaerobic treatment system has
      been erected. During a period of 100 days, after achieving steady state, the MBR
      system provided steady operation performance, while the activated sludge produced
      effluent characterized by oscillatory qualities. The following results, based on
      average values, indicate much lower suspended solids concentrations in the MBR
      effluent, 2.5 mg/L, as compared to 25 mg/L in the activated sludge. The ability
      to develop and maintain a concentration of over 11,000 mg/L of mixed liquor
      volatile suspended solids in the MBR enabled an intensive bioprocess at
      relatively high cell residence time. This study demonstrates that the anaerobic
      process, followed by aerobic MBR can provide effluent of high quality which can
      be considered for economic reuse in the paper mill industry.

PMID- 15461420
TI  - Evidence for recombination in the microcystin synthetase (mcy) genes of toxic
      cyanobacteria Microcystis spp.
AB  - Recombination has been suggested to be an important factor for the genetic
      variation of bacterial genes, but few studies have dealt with intragenic
      recombination between the same or closely related species of cyanobacteria. Here
      we provide strong evidence for recombination in the microcystin synthetase (mcy)
      gene cluster of the toxic cyanobacteria Microcystis spp. This gene cluster
      contains 10 genes (mcyA to J) that encode a mixed polyketide synthase
      (PKS)/nonribosomal peptide synthetase (NRPS) complex. mcy gene sequences were
      determined for four selected regions (within mcyA, D, G, and J) within the mcy
      gene cluster from 1 Canadian and 10 Asian toxic Microcystis and compared with
      previously published mcy sequences. Split decomposition analysis indicated a
      reticulate phylogeny of mcyA, and several potential recombination tracts of mcyA
      were identified by the RDP analysis and a runs test implemented in GENECONV. In
      contrast, no recombination was detected in the mcyD, G, and J sequences. However,
      discrepancies among the four mcy gene genealogies were evident from the results
      of independent split decomposition analyses, which were further supported by
      incongruence length difference (ILD) tests. Taken together, these findings
      suggest that both intragenic and intergenic recombination within the mcy gene
      cluster contributes to the genetic diversity of the mcy genes of Microcystis spp.

PMID- 15461421
TI  - Linkage of the beta-like omega-globin gene to alpha-like globin genes in an
      Australian marsupial supports the chromosome duplication model for separation of
      globin gene clusters.
AB  - The structure, function, and evolutionary history of globin genes have been the
      subject of extensive investigation over a period of more than 40 years, yet new
      globin genes with highly specialized functions are still being discovered and
      much remains uncertain about their evolutionary history. Here we investigate the
      molecular evolution of the beta-globin gene family in a marsupial species, the
      tammar wallaby, Macropus eugenii. We report the complete DNA sequences of two
      beta-like globin genes and show by phylogenetic analyses that one of these genes
      is orthologous to embryonically expressed epsilon-globin genes of marsupials and
      eutherians and the other is orthologous to adult expressed beta-globin genes of
      marsupials and eutherians. We show that the tammar wallaby contains a third
      functional beta-like globin gene, omega-globin, which forms part of the alpha
      globin gene cluster. The position of omega-globin on the 3' side of the alpha
      globin cluster and its ancient phylogenetic history fit the criteria, originally
      proposed by Jeffreys et al. (1980), of a "fossil" beta-globin gene and suggest
      that an ancient chromosome or genome duplication preceded the evolution of
      unlinked clusters of alpha- and beta-globin genes in mammals and avians. In
      eutherian mammals, such as humans and mice, omega-globin has been silenced or
      translocated away from the alpha-globin locus, while in marsupials omega-globin
      is coordinately expressed with the adult alpha-globin gene just prior to birth to
      produce a functional hemoglobin (alpha2 omega2).

PMID- 15461422
TI  - The decline of isochores in mammals: an assessment of the GC content variation
      along the mammalian phylogeny.
AB  - Whether isochores, the large-scale variation of the GC content in mammalian
      genomes, are being maintained has recently been questioned. It has been suggested
      that GC-rich isochores originated in the ancestral amniote genome but that
      whatever force gave rise to them is no longer effective and that isochores are
      now disappearing from mammalian genomes. Here we investigated the evolution of
      the GC content of 41 coding genes in 6 to 66 species of mammals by estimating the
      ancestral GC content using a method which allows for different rates of
      substitution between sites. We found a highly significant decrease in the GC
      content during early mammalian evolution, as well as a weaker but still
      significant decrease in the GC content of GC-rich genes later in at least three
      groups of mammals: primates, rodents, and carnivores. These results are of
      interest because they confirm the recently suggested disappearance of GC-rich
      isochores in some mammalian genomes, and more importantly, they suggest that this
      disappearance started very early in mammalian evolution.

PMID- 15461423
TI  - Bayesian estimation of positively selected sites.
AB  - In protein-coding DNA sequences, historical patterns of selection can be inferred
      from amino acid substitution patterns. High relative rates of nonsynonymous to
      synonymous changes (omega = dN/dS) are a clear indicator of positive, or
      directional, selection, and several recently developed methods attempt to
      distinguish these sites from those under neutral or purifying selection. One
      method uses an empirical Bayesian framework that accounts for varying selective
      pressures across sites while conditioning on the parameters of the model of DNA
      evolution and on the phylogenetic history. We describe a method that identifies
      sites under diversifying selection using a fully Bayesian framework. Similar to
      earlier work, the method presented here allows the rate of nonsynonymous to
      synonymous changes to vary among sites. The significant difference in using a
      fully Bayesian approach lies in our ability to account for uncertainty in
      parameters including the tree topology, branch lengths, and the codon model of
      DNA substitution. We demonstrate the utility of the fully Bayesian approach by
      applying our method to a data set of the vertebrate beta-globin gene. Compared to
      a previous analysis of this data set, the hierarchical model found most of the
      same sites to be in the positive selection class, but with a few striking
      exceptions.

PMID- 15461424
TI  - All roads lead to arginine: the squid protamine gene.
AB  - The protamine of squid is one of the most arginine-rich protamines (77%,
      mol/mol). It possesses a leading sequence that is posttranslationally removed
      during spermatogenesis in a manner that is analogous to that observed in some of
      its vertebrate protamine counterparts. In this paper we describe the gene
      sequence of the protamine of the squid Loligo opalescens. This represents the
      first complete gene sequence ever reported for an invertebrate protamine. Like
      those of vertebrate protamines, the messenger RNA is polyadenylated but the gene
      does not contain an intron. The promoter region contains the major
      transcriptional regulatory elements (CRE, TATA box, and CAP) that are also
      characteristic of the vertebrate protamine genes. It is unclear whether the
      similarities of protamines in species from both the deuterostome and the
      protostome branches represent the result of phylogenetic conservation or
      evolutionary convergence.

PMID- 15461425
TI  - The robustness of naturally and artificially selected nucleic acid secondary
      structures.
AB  - Thermodynamic stability and mutational robustness of secondary structure are
      critical to the function and evolutionary longevity of RNA molecules. We
      hypothesize that natural and artificial selection for functional molecules favors
      the formation of structures that are stable to both thermal and mutational
      perturbation. There is little direct evidence, however, that functional RNA
      molecules have been selected for their stability. Here we use thermodynamic
      secondary structure prediction algorithms to compare the thermal and mutational
      robustness of over 1000 naturally and artificially evolved molecules. Although we
      find evidence for the evolution of both types of stability in both sets of
      molecules, the naturally evolved functional RNA molecules were significantly more
      stable than those selected in vitro, and artificially evolved catalysts
      (ribozymes) were more stable than artificially evolved binding species
      (aptamers). The thermostability of RNA molecules bred in the laboratory is
      probably not constrained by a lack of suitable variation in the sequence pool
      but, rather, by intrinsic biases in the selection process.

PMID- 15461426
TI  - Cytosine methylation is not the major factor inducing CpG dinucleotide deficiency
      in bacterial genomes.
AB  - CpG dinucleotide deficiency has been found in viruses, mitochondria, prokaryotes,
      and eukaryotes. The consensual explanation is that it is due to deamination of
      methylated cytosines, as established for vertebrate and plants. However, we still
      do not know whether C5 cytosine methylation is also the major cause of CpG
      deficiency in bacteria. By combining annotation and experimental data identifying
      the presence of C5 cytosine methyltransferases with analysis of CpG relative
      abundance in 67 bacterial species, we found that CpG relative abundance in most
      bacterial genomes that have cytosine C5 methyltransferases tends to be in the
      normal range (observed/expected values between 0.82 and 1.21). In contrast, many
      bacterial species likely to be lacking C5 cytosine methylation showed CpG
      deficiency. Furthermore, when comparing genomes with one another, TpG and CpA
      relative abundances were found to be independent from CpG relative abundance.
      This contrasted with intragenome analyses, where C3pG1 relative abundance (the
      subscripts refer to position of a nucleotide in a codon) was found to be
      generally positively correlated with T3pG1 relative abundances when plotted
      against GC content in protein coding sequences (CDSs). This suggests the
      existence of alternative mechanisms contributing to CpG deficiency in bacteria.

PMID- 15461427
TI  - Evolution of programmed ribosomal frameshifting in the TERT genes of Euplotes.
AB  - A number of recent studies indicate that programmed + 1 ribosomal frameshifting
      is frequently required for the expression of genes in species of the genus
      Euplotes. In E. crassus, three genes encoding the telomerase reverse
      transcriptase (TERT) subunit have been previously found to possess one or two + 1
      frameshift sites. To examine the origin of frameshift sites within the Euplotes
      group, we have isolated segments of the TERT gene from five Euplotes species.
      Coupled with phylogenetic analysis, the results indicate that one frameshift site
      in the TERT gene arose late in the evolution of the group. In addition, a novel
      frameshift site was identified in the TERT gene of E. minuta, a species where
      frameshifting has not been previously reported. Coupled with other studies, the
      results indicate that frameshift sites have arisen during the diversification of
      the euplotids. The results also are discussed in regard to the mutations
      necessary to generate frameshift sites, and the specialization of TERT protein
      function that has apparently occurred in E. crassus.

PMID- 15461428
TI  - Presequence acquisition during secondary endocytobiosis and the possible role of
      introns.
AB  - Targeting of nucleus-encoded proteins into chloroplasts is mediated by N-terminal
      presequences. During evolution of plastids from formerly free-living
      cyanobacteria by endocytobiosis, genes for most plastid proteins have been
      transferred from the plastid genome to the nucleus and subsequently had to be
      equipped with such plastid targeting sequences. So far it is unclear how the gene
      domains coding for presequences and the respective mature proteins may have been
      assembled. While land plant plastids are supposed to originate from a primary
      endocytobiosis event (a prokaryotic cyanobacterium was taken up by a eukaryotic
      cell), organisms with secondary plastids like diatoms experienced a second
      endocytobiosis step involving a eukaryotic alga taken up by a eukaryotic host
      cell. In this group of algae, apparently most genes encoding chloroplast proteins
      have been transferred a second time (from the nucleus of the endosymbiont to the
      nucleus of the secondary host) and thus must have been equipped with additional
      targeting signals. We have analyzed cDNAs and the respective genomic DNA
      fragments of seven plastid preproteins from the diatom Phaeodactylum tricornutum.
      In all of these genes we found single spliceosomal introns, generally located
      within the region coding for the N-terminal plastid targeting sequences or
      shortly downstream of it. The positions of the introns can be related to the
      putative phylogenetic histories of the respective genes, indicating that the
      bipartite targeting sequences in these secondary algae might have evolved by
      recombination events via introns.

PMID- 15461429
TI  - Comparative analysis of Alu insertion sequences in the APP 5' flanking region in
      humans and other primates.
AB  - Overexpression of the amyloid precursor protein gene (APP) may play a role in the
      neuropathology of Alzheimer's disease. Therefore, elucidating the mechanisms
      involved in APP gene regulation is of primary importance, and various cis-acting
      regulatory elements located in 5' distal regions are known to play a main role.
      Some of them lie within Alu elements, one of which (Alu1) is only found in humans
      and apes while the other (Alu2) has a much older history and is also found in
      rhesus. These Alu insertions harbor sequence motifs that may act as cis
      regulatory elements, which may cause differences in APP regulation among primate
      species and whose functionality may be ascertained through their conservation in
      a comparative analysis. We have performed a comparative analysis of the region
      comprising the two Alu elements of the APP promoter in several primates,
      including humans. We have found a significant decrease in nucleotide diversity in
      the Alu2 element (inserted in all the species analyzed) compared to the Alu1
      (inserted only in apes). This finding can be interpreted as a constriction in the
      Alu2 sequence variation as a consequence of a functional role of this element in
      the APP expression. The present results suggest a wider extension of the
      regulatory elements than the known short consensus regulatory sequences.
      Moreover, the different conservation of two highly similar and neighboring
      sequences suggests that, besides the importance of the sequence motifs, their
      position in relation to the gene suggests that they have played a role in being
      recruited as regulatory elements.

PMID- 15461430
TI  - Molecular basis of the size polymorphism of the first intron of the Adh-1 gene of
      the mediterranean fruit fly, Ceratitis capitata.
AB  - The first intron of the gene encoding one of the alcohol dehydrogenase isoenzymes
      (ADH-1) in Ceratitis capitata is highly polymorphic in size. Five size variants
      of this intron were isolated from different strains and populations and
      characterized. Restriction map and sequence analysis showed that the intron size
      polymorphism is due to the presence or absence of (a) a copy of a defective
      mariner-like element, postdoc; (b) an approximately 550-bp 3' indel which
      exhibits no similarity to any known sequence; and (c) a central duplication of
      704 bp consisting of part of the 3' end of the postdoc element, the region
      between postdoc and the 3' indel, and the first 20 bp of the 3' indel. The
      homologous Adh-1 intron was amplified from the congeneric species, Ceratitis
      rosa, in order to obtain an outgroup for comparative and phylogenetic analyses.
      The C. rosa introns were polymorphic in size, ranging from about 1100 to 2000 bp,
      the major difference between them being the presence or absence of a mariner-like
      element Crmar2, unrelated to the postdoc element. Phylogenetic analysis suggests
      that the shorter intron variants in C. capitata may represent the ancestral form
      of the intron, the longest variants apparently being the most recent.

PMID- 15461431
TI  - Episodic molecular evolution of pituitary growth hormone in Cetartiodactyla.
AB  - The sequence of growth hormone (GH) is generally strongly conserved in mammals,
      but episodes of rapid change occurred during the evolution of primates and
      artiodactyls, when the rate of GH evolution apparently increased substantially.
      As a result the sequences of higher primate and ruminant GHs differ markedly from
      sequences of other mammalian GHs. In order to increase knowledge of GH evolution
      in Cetartiodactyla (Artiodactyla plus Cetacea) we have cloned and characterized
      GH genes from camel (Camelus dromedarius), hippopotamus (Hippopotamus amphibius),
      and giraffe (Giraffa camelopardalis), using genomic DNA and a polymerase chain
      reaction technique. As in other mammals, these GH genes comprise five exons and
      four introns. Two very similar GH gene sequences (encoding identical proteins)
      were found in each of hippopotamus and giraffe. The deduced sequence for the
      mature hippopotamus GH is identical to that of dolphin, in accord with current
      ideas of a close relationship between Cetacea and Hippopotamidae. The sequence of
      camel GH is identical to that reported previously for alpaca GH. The sequence of
      giraffe GH is very similar to that of other ruminants but differs from that of
      nonruminant cetartiodactyls at about 18 residues. The results demonstrate that
      the apparent burst of rapid evolution of GH occurred largely after the separation
      of the line leading to ruminants from other cetartiodactyls.

PMID- 15461433
TI  - Effects of anesthesia and vehicle injection on circulating blood elements in
      C3H/HeN male mice.
AB  - The induction and maintenance of general anesthesia can lead to profound
      alterations of many organ systems, especially the cardiovascular, pulmonary, and
      nervous systems. Moreover, distinct from their cardiopulmonary effects, certain
      anesthetics can induce physiologic and behavioral changes, which may persist
      after recovery from anesthesia. Knowledge of the effects of anesthesia and
      anesthetic agents on hematologic measurements is important. Although the effects
      of anesthesia were clinically unapparent, the effect on levels of circulating
      blood elements was an important determinant for the results of our study. We
      sought to evaluate the effect of anesthesia and vehicle injection on the levels
      of circulating blood elements in C3H/HeN male mice. We used an automated
      hematology system to obtain complete blood counts with differentials in
      anesthetized and unanesthetized mice receiving subcutaneous injections of
      polyethylene glycol (PEG-400). Two days after a 30-min exposure to isoflurane
      anesthesia, mean white blood cell counts had deceased by 15.4%, mean neutrophil
      counts had decreased by 26.9%, and mean platelet counts by 11.2% compared with
      levels in unanesthetized mice. Our results indicate that the effect of anesthesia
      is an important consideration when circulating blood elements in mice must be
      measured.

PMID- 15461432
TI  - Genetic divergence in the cacophony IVS6 intron among five Brazilian populations
      of Lutzomyia longipalpis.
AB  - Genes involved in the reproductive isolation are particularly useful as molecular
      markers in speciation studies. Lutzomyia longipalpis (Diptera: Psychodidae:
      Phlebotominae), a putative species complex, is a vector of visceral leishmaniasis
      in Latin America. We isolated from this species a fragment homologous to
      cacophony, a Drosophila gene that encodes features of the lovesong, an acoustic
      signal that is important in the sexual isolation of closely related species and
      known to vary considerably among L. longipalpis putative siblings species. Using
      an intron of the sandfly cacophony as a marker, we analyzed the molecular
      variation and sequence divergence among five populations of L. longipalpis from
      Brazil, three allopatric (Jacobina, Lapinha and Natal) and two putative sympatric
      sibling species from the locality of Sobral. A high level of polymorphism was
      found and analysis of the data indicates that very little gene flow is occurring
      among the populations of Jacobina, Lapinha, and Natal. A high level of
      differentiation was also observed between the two putative sympatric species of
      Sobral, one of which seems to be the same sibling species found in Natal, while
      the other is somewhat more related to Jacobina and Lapinha. However, the amount
      of estimated gene flow among the Sobral siblings is about seven times higher than
      the previously estimated for period, another lovesong gene, perhaps indicating
      that introgression might be affecting cacophony more than period. The results
      suggest that L. longipalpis is not a single species in Brazil, but it is yet not
      clear whether the different populations studied deserve species status rather
      than representing an incipient speciation process.

PMID- 15461434
TI  - Comparison of body surface temperature measurement and conventional methods for
      measuring temperature in the mouse.
AB  - Temperature is a valuable parameter used to judge wellness of animals in a
      research setting; therefore, reliable, noninvasive, and inexpensive methods for
      monitoring temperature are becoming a necessity in research laboratories. A new
      method for obtaining temperature in mice, the measurement of body surface
      temperature via an external probe, was compared to two more common methods, the
      rectal probe and telemetry. The comparisons of the temperature measuring devices
      were performed in mice made hypothermic via prolonged anesthesia and in mice made
      hyperthermic by injection of endotoxin. The results demonstrated good correlation
      between the surface temperature measurements and the temperatures obtained by
      both telemetry and the rectal probe. The correlations were particularly
      significant when core body temperatures were below normal. In addition, the
      surface probe compared favorably with the other methods with regard to animal
      stress, observed complications, and initial cost. These results suggest that the
      surface probe could provide an efficient means for obtaining valuable
      physiological data and determining humane endpoints.

PMID- 15461435
TI  - Persistent shedding of mouse hepatitis virus in mouse lines selected for genetic
      differences in alcohol sensitivity.
AB  - Two replicate lines of mice, selected for hyperactivity and hypoactivity after
      ethanol administration, had been enzootically infected with mouse hepatitis virus
      (MHV) for over a decade. A cessation of breeding program (also known as a
      "burnout") was implemented to eradicate the virus and was successful in only one
      of the four lines. Subsequent investigation demonstrated persistent shedding of
      MHV in two lines of mice for at least 7 weeks. To the author's knowledge, this is
      the first documented case of clinically inapparent persistent shedding of MHV in
      mice that are not genetically engineered.

PMID- 15461436
TI  - Multi-phase approach to eradicate enzootic mouse coronavirus infection.
AB  - Infections with mouse coronavirus (also known as mouse hepatitis virus, MHV) are
      common and prompt concern because the adverse research effects of infection have
      been well documented. The animal facility we describe had contained an enzootic
      infection of mouse coronavirus for more than a decade. Eradication of the virus
      had been tried with limited success in the past. With an increase in the
      populations of immune-compromised and transgenic animals elsewhere in the
      facility, eradication of the virus became a high priority. The affected animals
      were in multiple breeding colonies comprising more than 4000 mice representing
      more than 50 site-specific strains, lines, and sublines. A task force designed to
      ensure representation of all interested parties developed a multi-phase approach
      which included (a) culling of nonessential animals, (b) cessation of breeding,
      (c) testing and culling of individual animals, and (d) cross-fostering to clean
      dams. To date, all of the strains, lines, and sublines manipulated through this
      multi-phase eradication approach continue to test negative for mouse coronavirus.
      This multi-phase approach may be useful for other institutions attempting to
      eradicate mouse coronavirus.

PMID- 15461437
TI  - Euthanasia of mouse fetuses and neonates.
AB  - We sought to determine whether any of the common methods of euthanasia for adult
      rodents would lead to an acceptable death for fetuses or neonates. We wanted to
      identify a method that was rapid, free of signs of pain or distress, reliable,
      and minimally distressful to the person performing the procedure and that
      minimized the amount of handling required to perform the procedure. We evaluated
      six methods of euthanasia, with and without anesthesia, in three age groups of
      mice: gravid mice (E14-20) and neonatal pups (P1-P7 and P8-P14). Euthanasia
      methods included: halothane inhalation, carbon dioxide inhalation,
      intraperitoneal sodium pentobarbital, intravenous potassium chloride, and
      cervical dislocation with and without anesthesia. Noninvasive echocardiography
      was used to assess heartbeat during euthanasia. With cardiac arrest as the
      definition of death, no method of euthanasia killed fetal mice. Halothane
      inhalation (5% by vaporizer) was not an acceptable method of euthanasia for mice
      of the age groups tested. Intraperitoneal administration of sodium pentobarbital
      for euthanasia required a higher dose than the previously established dose, and
      there is a risk of reduced efficacy in pregnant animals due to potential
      intrauterine injection. Carbon dioxide asphyxiation was the most efficient method
      of euthanasia for neonatal mouse pups P1-14. For pregnant adult mice, intravenous
      potassium chloride under anesthesia, carbon dioxide asphyxiation, and cervical
      dislocation alone or under anesthesia were excellent methods of euthanasia.

PMID- 15461438
TI  - The use of the hairless guinea pig in tattoo research.
AB  - The study and optimization of tattoo removal continues to be of importance in the
      dermatology community. Robust animal models whose skin is physiologically similar
      to humans and who are easily handled are desirable. To this end, we report on our
      experience with the hairless guinea pig as a model for tattoo research. This
      research was conducted as part of a larger study toward increased efficacy of
      laser tattoo removal. Here we report on procedures for both placement and
      aftercare of tattoos which result in superior tattoo quality and retention.

PMID- 15461439
TI  - Comparison of pH measurement devices for determining vaginal pH in cynomolgus
      macaques.
AB  - When designing, developing, and testing pharmaceutical compounds, scientists rely
      on available data about the environmental pH of the target organ--in this case,
      the vaginal tract--for determining maximum absorption. In this study, we compared
      two commercially available pH papers with a handheld digital pH meter to assess
      their viability as methods for measuring vaginal pH in cynomolgus monkeys. We
      sedated 17 female cynomolgus monkeys (Macaca fascicularis) and measured their
      vaginal pH by using the three described devices. The results were comparable, and
      there were no significant difference among the three methods used; however, the
      color and consistency of the vaginal fluid and the visual acuity of the user did
      not affect the results measured using the handheld digital pH meter. We conclude
      that the handheld digital pH meter is a viable method for measuring vaginal pH in
      cynomolgus monkeys.

PMID- 15461440
TI  - Fostering procedures for orphaned infants in a breeding colony of African green
      monkeys.
AB  - We developed procedures to foster orphaned African green monkey infants to
      females with natural infants of a similar age to the foster infant (< 1 month).
      Our purpose was to assess the feasibility of fostering additional infants to
      females with natural infants. The subjects were 4 infants (age 1 to 5 days) that
      were removed from the natural mother because of neglect or trauma. The recipient
      females varied in parity (0 to 7 previous infants). Within 24 h of removal from
      the natural mother, the foster infants were presented to a group of potential
      recipient females by placing the foster infant directly into the cage of the
      female that demonstrated positive behavior toward the foster infant (reaching
      toward the infant and lip-smacking). Analysis of the behavioral data collected
      when the infants were 3 to 6 months of age indicated that foster mothers spent
      significantly more time nursing the natural infant alone, but the percentage time
      spent nursing both infants simultaneously was not significantly different than
      the time spent nursing either infant individually. No significant differences
      between weaning weight of the natural and foster infants or single infants were
      observed at 6 months of age. Overall our success rate at weaning (75%) suggests
      that fostering additional infants on females with a natural infant may be a
      viable strategy for raising orphaned African green monkeys and may prevent the
      development of abnormal behaviors that typically are manifested by nursery-reared
      infants.

PMID- 15461441
TI  - Hebb-Williams mazes.

PMID- 15461442
TI  - Topological and conformational analysis of the initiation and elongation complex
      of t7 RNA polymerase suggests a new twist.
AB  - The N-terminal domain of T7 RNA polymerase undergoes large conformational changes
      in the transition from transcription initiation to elongation. The rigid body
      displacement of parts of the N-terminal domain (residues 72-152 and 204-258) has
      been described as a screw motion composed of a rotation by 140 degrees and a
      translation of >20 A along the rotation axis. Protein-protein interactions
      between residues 23-42 and the C-terminal domain are present in both the
      initiation and the elongation complex. Assuming that these interactions are
      retained during the transition between the two states, we find that topological
      constraints require a right-handed 220 degrees screw motion of the N-terminal
      rigid body rather than the proposed 140 degrees left-handed screw motion. In the
      initiation complex, a loop (residues 153-203) extruding from the N-terminal rigid
      domain wraps around the N-terminal 30 residues. Assuming the N-terminal rigid
      domain stays folded during the transition, the N-terminus has to pass through
      this loop before the rigid domain can undergo the translation leading to the
      elongation complex. On the basis of these topological constraints, we suggest an
      alternate sequence of conformational changes leading from transcription
      initiation to elongation in T7 polymerase.

PMID- 15461443
TI  - Topogenesis of membrane proteins at the endoplasmic reticulum.
AB  - Most eukaryotic membrane proteins are cotranslationally integrated into the
      endoplasmic reticulum membrane by the Sec61 translocation complex. They are
      targeted to the translocon by hydrophobic signal sequences, which induce the
      translocation of either their N- or their C-terminal sequence. Signal sequence
      orientation is largely determined by charged residues flanking the apolar
      sequence (the positive-inside rule), folding properties of the N-terminal
      segment, and the hydrophobicity of the signal. Recent in vivo experiments suggest
      that N-terminal signals initially insert into the translocon head-on to yield a
      translocated N-terminus. Driven by a local electrical potential, the signal may
      invert its orientation and translocate the C-terminal sequence. Increased
      hydrophobicity slows down inversion by stabilizing the initial bound state. In
      vitro cross-linking studies indicate that signals rapidly contact lipids upon
      entering the translocon. Together with the recent crystal structure of the
      homologous SecYEbeta translocation complex of Methanococcus jannaschii, which did
      not reveal an obvious hydrophobic binding site for signals within the pore, a
      model emerges in which the translocon allows the lateral partitioning of
      hydrophobic segments between the aqueous pore and the lipid membrane. Signals may
      return into the pore for reorientation until translation is terminated.
      Subsequent transmembrane segments in multispanning proteins behave similarly and
      contribute to the overall topology of the protein.

PMID- 15461444
TI  - On the solution structure of the T4 sliding clamp (gp45).
AB  - Examination by time-resolved fluorescence spectroscopy of the trimeric
      bacteriophage T4 clamp protein labeled across its three subunit interfaces with a
      fluorescence resonance energy transfer (FRET) pair indicates that the clamp
      exists in just one state in solution, with one open and two closed interfaces.
      This is in contrast to what is observed in the X-ray crystal structure. The
      population distribution of the trFRET distance is bimodal, giving 67% as 17 A and
      33% as 42 A. This leads to the conclusion that gp45 exists in an asymmetric open
      state in solution. The further increase in the separation of the FRET pair in the
      presence of the clamp loader and ATP may be ascribed to either further opening of
      the open interface or the opening of a closed interface. The ramifications for
      replisome remodeling by this pathway are discussed.

PMID- 15461445
TI  - Kinetics and thermodynamics of RRF, EF-G, and thiostrepton interaction on the
      Escherichia coli ribosome.
AB  - Ribosome recycling factor (RRF) and elongation factor-G (EF-G) are jointly
      essential for recycling bacterial ribosomes following termination of protein
      synthesis. Here we present equilibrium and rapid kinetic measurements permitting
      formulation of a minimal kinetic scheme that accounts quantitatively for RRF and
      EF-G interaction on the Escherichia coli ribosome. RRF and EF-G (a) each form a
      binary complex on binding to a bare ribosome which undergoes isomerization to a
      more stable complex, (b) form mixed ternary complexes on the ribosome in which
      the affinity for each factor is considerably lower than its affinity for binding
      to a bare ribosome, and (c) each bind to two sites per ribosome, with EF-G having
      considerably higher second-site affinity than RRF. Addition of EF-G to the
      ribosome-RRF complex induces rapid RRF dissociation, at a rate compatible with
      the rate of ribosome recycling in vivo, but added RRF does not increase the
      lability of ribosome-bound EF-G. Added thiostrepton slows the initial binding of
      EF-G, and prevents both formation of the more stable EF-G complex and EF-G
      induced RRF dissociation. These findings are relevant for the mechanism of post
      termination complex disassembly.

PMID- 15461446
TI  - High-resolution protein-DNA contacts for the yeast RNA polymerase II general
      transcription machinery.
AB  - We used site-specific protein-DNA photo-cross-linking to define contact points
      between Saccharomyces cerevisiae RNA polymerase II (RNAP II) and the general
      transcription factors TBP, TFIIB, and TFIIF on promoter DNA. We present three key
      findings: (i) the overall pattern of cross-link sites is remarkably similar
      between the yeast and the previously described human system, even though
      transcription initiates downstream of the DNA-TBP-TFIIB-RNAP II-TFIIF complex in
      the S. cerevisiae system; (ii) the yeast Rpb7 subunit of RNAP II forms strong and
      reproducible cross-links to both strands of promoter DNA; and (iii) a TFIIB
      arginine-78 to cysteine replacement (R78C), which shifts start site selection
      downstream of normal, does not affect TFIIB-DNA cross-links prior to promoter
      melting but instead affects downstream TFIIF-DNA interactions. These results
      support the premise that the overall structure of the RNAP II preinitiation
      complex is similar in all eukaryotes and imply that yeast RNAP II is able to scan
      template DNA downstream of the preinitiation complex for acceptable start sites.
      The novel Rpb7-DNA contact sites imply that either promoter DNA does not follow a
      straight path from TATA to the initiation site or the topology of Rpb7 within the
      DNA-TBP-TFIIB-RNAP II-TFIIF complex is different from that defined in the 12
      subunit RNAP II X-ray structure. We discuss the implications of these results for
      the mechanism of preinitiation complex assembly and promoter melting.

PMID- 15461447
TI  - Assembly of major histocompatibility complex (MHC) class II transcription
      factors: association and promoter recognition of RFX proteins.
AB  - Major histocompatibility complex (MHC) class II genes are regulated at the
      transcriptional level by coordinate action of a limited number of transcription
      factors that include regulatory factor X (RFX), class II transcriptional
      activator (CIITA), nuclear factor Y (NF-Y), and cyclic AMP-response element
      binding protein (CREB). Here, the MHC class-II-specific transcription factors and
      CREB were expressed in insect cells with recombinant baculoviruses, isolated, and
      characterized by biochemical and biophysical methods. Analytical
      ultracentrifugation (AUC) has demonstrated that RFX is a heterotrimer. A
      heterodimer of RFX5 and RFX-AP was also observed. A high-affinity interaction
      (K(d) = 25 nM) between RFX5 and RFX-AP was measured by isothermal titration
      calorimetry (ITC), while the interaction between RFX-AP and RFX-ANK is at least
      an order of magnitude weaker. The biophysical data show that the interaction
      between RFX-AP and RFX5 is a key event in the assembly of the heterotrimer.
      Fluorescence anisotropy was used to determine protein-nucleic acid binding
      affinities for the RFX subunits and complexes binding to duplex DNA. The RFX5
      subunit was found to drive recognition of the promoter, while the auxiliary RFX
      AP and RFX-ANK subunits were shown to contribute to the specificity of binding
      for the overall complex. AUC experiments demonstrate that in the absence of
      additional subunits, monomeric RFX5 binds to X-box DNA with a 1:1 stoichiometry.
      Interactions between CREB, CIITA, and RFX in the absence of DNA were demonstrated
      using bead-based immunoprecipitation assays, confirming that preassociation with
      DNA is not required for forming the macromolecular assemblies that drive MHC
      class II gene expression.

PMID- 15461448
TI  - A novel antioxidant role for ligandin behavior of glutathione S-transferases:
      attenuation of the photodynamic effects of hypericin.
AB  - Hypericin (HYP) is a major constituent of the herbal antidepressant St. John's
      wort with potential utility as an antitumor photodynamic sensitizer and antiviral
      agent. Upon irradiation at 540-600 nm, HYP generates reactive oxygen species
      (ROS) and induces oxidative stress. Here, human glutathione S-transferase (GST)
      isoforms GSTP1-1 (P1-1) and GSTA1-1 (A1-1) are shown to bind with high affinity
      to HYP and to differentially quench its photodynamic properties. In steady-state
      turnover studies, HYP inhibits A1-1 and P1-1 with IC(50) values of 160 and 190
      nM, respectively. Fluorescence titration experiments and fitting of the data to
      the Hill equation yield apparent K(D)s for binding to A1-1 and P1-1 of 0.65 and
      0.51 microM, respectively. The recovered Hill coefficients are 1.8 for both GSTA1
      1 and GSTP1-1, indicating that multiple HYPs bind to each isoform. This behavior
      is reminiscent of classic "ligandin" activity of GSTs, wherein nonsubstrate
      planar aromatic anions are sequestered on, and inhibit, the enzyme. However, HYP
      complexed with P1-1 is photodynamically attenuated, with minimal protein
      oxidation. In contrast, light-dependent, oxygen-dependent, oxidation of A1-1 was
      modest and oxidation of human albumin was extensive in the presence of HYP, as
      monitored by electrospray mass spectrometry (ESI-MS). A peptide "trap" of
      diffusive ROS was oxidized extensively upon irradiation of HYP in the presence of
      albumin but very little in the presence of P1-1 or A1-1. Solute quenching studies
      were used to probe the accessibility of the bound HYP in each of the protein
      complexes. The fluorescence of HYP complexed with albumin, A1-1, or P1-1 was
      quenched by I(-) with quenching rate constants (k(q)) of 1.1 x 10(9), 2.4 x 10(9)
      and 0.5 x10(9) M(-1) s(-1), respectively, indicating that small molecules such as
      O(2) have similar diffusional access to the complexed HYP in each of the
      proteins, eliminating the possibility of differential accessibility of oxygen as
      the source of a different yield of ROS. This is the first demonstration of a
      possible antioxidant role for the ligandin activity of GSTs and a striking
      example of protein-specific effects on hypericin photodynamic activity. Even
      highly homologous protein isoforms can differentially promote or inhibit
      photosensitizer activity.

PMID- 15461449
TI  - X-ray crystal structure of the hypothetical phosphotyrosine phosphatase MDP-1 of
      the haloacid dehalogenase superfamily.
AB  - The haloacid dehalogenase (HAD) superfamily is comprised of structurally
      homologous enzymes that share several conserved sequence motifs (loops I-IV) in
      their active site. The majority of HAD members are phosphohydrolases and may be
      divided into three subclasses depending on domain organization. In classes I and
      II, a mobile "cap" domain reorients upon substrate binding, closing the active
      site to bulk solvent. Members of the third class lack this additional domain.
      Herein, we report the 1.9 A X-ray crystal structures of a member of the third
      subclass, magnesium-dependent phosphatase-1 (MDP-1) both in its unliganded form
      and with the product analogue, tungstate, bound to the active site. The secondary
      structure of MDP-1 is similar to that of the "core" domain of other type I and
      type II HAD members with the addition of a small, 28-amino acid insert that does
      not close down to exclude bulk solvent in the presence of ligand. In addition,
      the monomeric oligomeric state of MDP-1 does not allow the participation of a
      second subunit in the formation and solvent protection of the active site. The
      binding sites for the phosphate portion of the substrate and Mg(II) cofactor are
      also similar to those of other HAD members, with all previously observed contacts
      conserved. Unlike other subclass III HAD members, MDP-1 appears to be equally
      able to dephosphorylate phosphotyrosine and closed-ring phosphosugars. Modeling
      of possible substrates in the active site of MDP-1 reveals very few potential
      interactions with the substrate leaving group. The mapping of conserved residues
      in sequences of MDP-1 from different eukaryotic organisms reveals that they
      colocalize to a large region on the surface of the protein outside the active
      site. This observation combined with the modeling studies suggests that the
      target of MDP-1 is most likely a phosphotyrosine in an unknown protein rather
      than a small sugar-based substrate.

PMID- 15461450
TI  - Narrowing substrate specificity in a directly evolved enzyme: the A293D mutant of
      aspartate aminotransferase.
AB  - Several mutant Escherichia coli aspartate aminotransferases (eAATases) have been
      characterized in the attempt to evolve or rationally redesign the substrate
      specificity of eAATase into that of E. coli tyrosine aminotransferase (eTATase).
      These include HEX (designed), HEX + A293D (design followed by directed
      evolution), and SRHEPT (directed evolution). The A293D mutation realized from
      directed evolution of HEX is here imported into the SRHEPT platform by site
      directed mutagenesis, resulting in an enzyme (SRHEPT + A293D) with nearly the
      same ratio of k(cat)/K(m)(Phe) to k(cat)/K(m)(Asp) as that of wild-type eTATase.
      The A293D substitution is an important specificity determinant; it selectively
      disfavors interactions with dicarboxylic substrates and inhibitors compared to
      aromatic ones. Context dependence analysis is generalized to provide quantitative
      comparisons of a common substitution in two or more different protein scaffolds.
      High-resolution crystal structures of ligand complexes of HEX + A293D, SRHEPT,
      and SRHEPT + A293D were determined. We find that in both SRHEPT + A293D and HEX +
      A293D, the additional mutation holds the Arg 292 side chain away from the active
      site to allow increased specificity for phenylalanine over aspartate. The
      resulting movement of Arg 292 allows greater flexibility of the small domain in
      HEX + A293D. While HEX is always in the closed conformation, HEX + A293D is
      observed in both the closed and a novel open conformation, allowing for more
      rapid product release.

PMID- 15461451
TI  - Phosphorylation of calmodulin fragments by protein kinase CK2. Mechanistic
      aspects and structural consequences.
AB  - Calmodulin is phosphorylated in vivo and in vitro by protein kinase CK2 in a
      manner that is unique among CK2 substrates for being inhibited by the regulatory
      beta-subunit of the kinase and dramatically enhanced by polybasic peptides. Using
      synthetic fragments of calmodulin variably encompassing the CK2 phosphorylation
      sites here we show that individual phosphorylation of Thr79, Ser81, Ser101, and
      Thr117 is critically influenced by the size and composition of the peptides and
      that the C-terminal domain of calmodulin is implicated both in down-regulation of
      calmodulin phosphorylation by the beta-subunit and in its abnormal responsiveness
      to polylysine. A far-Western blot analysis discloses polylysine-dependent
      interaction between calmodulin and the N-terminal domain of the beta-subunit. We
      also show that phosphorylation of Ser81 hampers subsequent phosphorylation of
      Thr79 and by itself promotes the unfolding of the central helix, whose
      flexibility is instrumental to the interaction with calmodulin-dependent enzymes.
      Collectively taken, our data are consistent with a multifaceted regulation of
      calmodulin phosphorylation through the concerted action of distinct CaM domains,
      the catalytic and regulatory subunits of CK2, and polycationic effectors
      mimicking in vivo the effect of polylysine.

PMID- 15461452
TI  - Rates of the phthalate dioxygenase reaction with oxygen are dramatically
      increased by interactions with phthalate and phthalate oxygenase reductase.
AB  - The phthalate dioxygenase system, which catalyzes the dihydroxylation of
      phthalate to form its cis-dihydrodiol (DHD), has two components: phthalate
      dioxygenase (PDO), a multimer with one Rieske-type [2Fe-2S] and one Fe(II) center
      per monomer, and phthalate dioxygenase reductase (PDR), which contains flavin
      mononucleotide (FMN) and a plant-like ferredoxin [2Fe-2S] center. PDR is
      responsible for transferring electrons from NADH to the Rieske center of PDO, and
      the Rieske center supplies electrons to the mononuclear center for the
      oxygenation of substrate. Reduced PDO (PDO(red)) that lacks Fe(II) at the
      mononuclear metal site (PDO-APO) reacts slowly with O(2) (1.4 x 10(-3) s(-1) at
      125 microM O(2) and 22 degrees C), presumably in a direct reaction with the
      Rieske center. Binding of phthalate and/or PDR(ox) to reduced PDO-APO increases
      the reactivity of the Rieske center with O(2). When no PDR or phthalate is
      present, the oxidation of the Rieske center in native PDO(red) [which contains
      Fe(II) at the mononuclear site] occurs in two phases (approximately 1 and 0.1 s(
      1) at 125 mM O(2), 23 degrees C), both much faster than in the absence of Fe(II),
      presumably because in this case O(2) reacts at the mononuclear Fe(II). Addition
      of PDR(ox) to native PDO(red) resulted in a large fraction of the Rieske center
      being oxidized at 5 s(-1), and the addition of phthalate resulted in about 70% of
      the reaction proceeding at 42 s(-1). With both PDR(ox) and phthalate present,
      most of the PDO(red) (approximately 80-85%) oxidizes at 42 s(-1), with the
      remaining oxidizing at approximately 5 s(-1). Thus, the binding of phthalate or
      PDR(ox) to PDO(red) each results in greater reactivity of PDO with O(2). The
      presence of both the substrate and PDR was synergistic, making PDO fully
      catalytically active. A model that explains the observed effects is presented and
      discussed in terms of PDO subunit cooperativity. It is proposed that, during
      oxidation of reduced PDO, each of two Rieske centers on separate subunits
      transfers an electron to the Fe(II) mononuclear center on a third subunit. This
      explanation is consistent with the observed multiphasic kinetics of the oxidation
      of the Rieske center and is being further tested by product analysis experiments.

PMID- 15461453
TI  - Role of arginine-82 in fast proton release during the bacteriorhodopsin
      photocycle: a time-resolved FT-IR study of purple membranes containing 15N
      labeled arginine.
AB  - Arginine-82 has long been recognized as an important residue in bacteriorhodopsin
      (bR), because its mutation usually results in loss of fast H(+) release, an
      important step in the normal light-induced H(+) transport mechanism. To help to
      clarify the structural changes in Arg-82 associated with the H(+)-release step,
      we have measured time-resolved FT-IR difference spectra of wild-type bR
      containing either natural-abundance isotopes ((14)N-Arg-bR) or all seven
      arginines selectively and uniformly labeled with (15)N at the two eta-nitrogens
      ((15)N-Arg-bR). Comparison of the spectra from the two isotopic variants shows
      that a 1556 cm(-1) vibrational difference band due to the M photocycle
      intermediate of (14)N-Arg-bR loses substantial intensity in (15)N-Arg-bR.
      However, this isotope-sensitive arginine vibrational difference band is only
      observed at pH 7 and not at pH 4 where fast H(+) release is blocked. These
      observations support the earlier conclusion, based on site-directed mutagenesis
      and chemical labeling, that a strong C-N stretch vibration of Arg-82 can be
      assigned to a highly perturbed frequency near 1555 cm(-1) in the M state of wild
      type bR [Hutson et al. (2000) Biochemistry 39, 13189-13200]. Furthermore,
      alkylguanidine model compound spectra indicate that the unusually low arginine C
      N stretch frequency in the M state is consistent with a nearly stoichiometric
      light-induced deprotonation of an arginine side chain within bR, presumably
      arginine-82.

PMID- 15461454
TI  - Deuterium NMR structure of retinal in the ground state of rhodopsin.
AB  - The conformation of retinal bound to the G protein-coupled receptor rhodopsin is
      intimately linked to its photochemistry, which initiates the visual process. Site
      directed deuterium ((2)H) NMR spectroscopy was used to investigate the structure
      of retinal within the binding pocket of bovine rhodopsin. Aligned recombinant
      membranes were studied containing rhodopsin that was regenerated with retinal
      (2)H-labeled at the C(5), C(9), or C(13) methyl groups by total synthesis.
      Studies were conducted at temperatures below the gel to liquid-crystalline phase
      transition of the membrane lipid bilayer, where rotational and translational
      diffusion of rhodopsin is effectively quenched. The experimental tilt series of
      (2)H NMR spectra were fit to a theoretical line shape analysis [Nevzorov, A. A.,
      Moltke, S., Heyn, M. P., and Brown, M. F. (1999) J. Am. Chem. Soc. 121, 7636
      7643] giving the retinylidene bond orientations with respect to the membrane
      normal in the dark state. Moreover, the relative orientations of pairs of methyl
      groups were used to calculate effective torsional angles between different planes
      of unsaturation of the retinal chromophore. Our results are consistent with
      significant conformational distortion of retinal, and they have important
      implications for quantum mechanical calculations of its electronic spectral
      properties. In particular, we find that the beta-ionone ring has a twisted 6-s
      cis conformation, whereas the polyene chain is twisted 12-s-trans. The
      conformational strain of retinal as revealed by solid-state (2)H NMR is
      significant for explaining the quantum yields and mechanism of its ultrafast
      photoisomerization in visual pigments. This work provides a consensus view of the
      retinal conformation in rhodopsin as seen by X-ray diffraction, solid-state NMR
      spectroscopy, and quantum chemical calculations.

PMID- 15461455
TI  - Stability of loops in the structure of lactose permease.
AB  - Structural analysis of peptide fragments has provided useful information on the
      secondary structure of integral membrane proteins built from a helical bundle (up
      to seven transmembrane segments). Comparison of those results to recent X-ray
      crystallographic results showed agreement between the structures of the fragments
      and the structures of the intact proteins. Lactose permease of Escherichia coli
      (lac Y) offers an opportunity to test that hypothesis on a substantially larger
      integral membrane protein. Lac Y contains a bundle of 12 transmembrane segments
      connected by 11 loops. Eleven segments, each corresponding to one of the loops in
      this protein, were studied. Five of these segments form defined structures in
      solution as determined by multidimensional nuclear magnetic resonance. Four
      peptides form turns, and one peptide reveals the end of one of the transmembrane
      helices. These results suggest that some loops in helical bundles are stabilized
      by short-range interactions, particularly in smaller bundles, and such
      intrinsically stable loops may contribute to protein stability and influence the
      pathway of folding. Greater conformational flexibility may be found in large
      integral membrane proteins.

PMID- 15461456
TI  - Calcium-induced conformational changes in the C-terminal half of gelsolin
      stabilize its interaction with the actin monomer.
AB  - The basic mechanism for the nucleating effect of gelsolin on actin polymerization
      is the formation of a complex of gelsolin with two actin monomers. Probably due
      to changes in the C-terminal part of gelsolin, a stable ternary complex is only
      formed at [Ca(2+)] >10(-5) M [Khaitlina, S., and Hinssen, H. (2002) FEBS Lett.
      521, 14-18]. Therefore, we have studied the binding of actin monomer to the
      isolated C-terminal half of gelsolin (segments 4-6) over a wide range of calcium
      ion concentrations to correlate the conformational changes to the complex
      formation. With increasing [Ca(2+)], the apparent size of the C-terminal half as
      determined by gel filtration was reduced, indicating a transition into a more
      compact conformation. Moreover, Ca(2+) inhibited the cleavage by trypsin at Lys
      634 within the loop connecting segments 5 and 6. Though the inhibitory effect was
      observed already at [Ca(2+)] of 10(-7) M, it was enhanced with increasing
      [Ca(2+)], attaining saturation only at >10(-4) M Ca(2+). This indicates that the
      initial conformational changes are followed by additional molecular transitions
      in the range of 10(-5)-10(-4) M [Ca(2+)]. Consistently, preformed complexes of
      actin with the C-terminal part of gelsolin became unstable upon lowering the
      calcium ion concentrations. These data provide experimental support for the role
      of the type 2 Ca-binding sites in gelsolin segment 5 proposed by structural
      studies [Choe et al. (2002) J. Mol. Biol. 324, 691]. We assume that the observed
      structural transitions contribute to the stable binding of the second actin
      monomer in the ternary gelsolin-actin complex.

PMID- 15461457
TI  - SERCA structural dynamics induced by ATP and calcium.
AB  - We have used time-resolved phosphorescence anisotropy (TPA) to probe rotational
      dynamics of the rabbit skeletal sarcoplasmic reticulum Ca-ATPase (SERCA), to test
      the hypothesis, generated from X-ray crystallography, that large-scale structural
      changes are induced by Ca in this system. Previous TPA studies on SERCA used
      primarily erythrosin 5'-isothiocyanate (ErITC), which binds to the nucleotide
      binding domain and inactivates the enzyme. To investigate rotational dynamics of
      the active enzyme, we labeled SERCA with erythrosin 5'-iodoacetamide, which binds
      to the phosphorylation domain and has a minimal effect on the calcium-dependent
      ATPase activity. In the absence of nucleotide and the presence of calcium, TPA
      results were similar to those observed previously with ErITC, consistent with the
      global uniaxial rotation of SERCA monomers and oligomers and small amplitude
      internal protein dynamics. The removal of Ca had only a slight effect, while the
      addition of adenosine 5'-triphosphate (ATP) increased the amplitude of internal
      dynamics and changed the probe's orientation, corresponding to tilting of the
      phosphorylation domain by at least 20 degrees . Ca partially reversed the ATP
      effects. A nonhydrolyzable ATP analogue had the same effects as ATP, showing that
      the observed changes were not dependent on active ion transport. Computational
      analysis indicates that these ligands affect primarily the internal dynamics of
      the enzyme, with negligible effects on global dynamics and enzyme association.
      Melittin, which has been shown to aggregate and inhibit SERCA, eliminated the
      nucleotide-induced internal dynamics and increased the final anisotropy. We
      propose that (i) the large Ca-dependent structural changes suggested by SERCA
      crystallography are more dependent on ATP than on Ca and (ii) aggregation-induced
      inhibition of SERCA is due to the functional coupling between global and internal
      protein dynamics.

PMID- 15461458
TI  - Thermal unfolding of Apo and Holo Desulfovibrio desulfuricans flavodoxin:
      cofactor stabilizes folded and intermediate states.
AB  - We here compare thermal unfolding of the apo and holo forms of Desulfovibrio
      desulfuricans flavodoxin, which noncovalently binds a flavin mononucleotide (FMN)
      cofactor. In the case of the apo form, fluorescence and far-UV circular dichroism
      (CD) detected transitions are reversible but do not overlap (T(m) of 50 and 60
      degrees C, respectively, pH 7). The thermal transitions for the holo form follow
      the same pattern but occur at higher temperatures (T(m) of 60 and 67 degrees C
      for fluorescence and CD transitions, respectively, pH 7). The holoprotein
      transitions are also reversible and exhibit no protein concentration dependence
      (above 10 microM), indicating that the FMN remains bound to the polypeptide
      throughout. Global analysis shows that the thermal reactions for both apo and
      holo forms proceed via an equilibrium intermediate that has approximately 90%
      nativelike secondary structure and significant enthalpic stabilization relative
      to the unfolded states. Incubation of unfolded holoflavodoxin at high
      temperatures results in FMN dissociation. Rebinding of FMN at these conditions is
      nominal, and therefore, cooling of holoprotein heated to 95 degrees C follows the
      refolding pathway of the apo form. However, FMN readily rebinds to the apoprotein
      at lower temperatures. We conclude that (1) a three-state thermal unfolding
      behavior appears to be conserved among long- and short-chain, as well as apo and
      holo forms of, flavodoxins and (2) flavodoxin's thermal stability (in both native
      and intermediate states) is augmented by the presence of the FMN cofactor.

PMID- 15461459
TI  - Factors affecting thermodynamic stabilities of RNA 3 x 3 internal loops.
AB  - Internal loops in RNA are important for folding and function. The 3 x 3
      nucleotide internal loops are the smallest size symmetric loops with a potential
      noncanonical base pair (middle pair) flanked on both sides by a noncanonical base
      pair (loop-terminal pair). Thermodynamic and structural insights acquired for 3 x
      3 loops should improve approximations for stabilities of 3 x 3 and larger
      internal loops. Most natural 3 x 3 internal loops are purine rich, which is also
      true of other internal loops. A series of oligoribonucleotides containing
      different 3 x 3 internal loops were studied by UV melting and imino proton NMR.
      Both loop-terminal and middle pairs contribute to the thermodynamic stabilities
      of 3 x 3 loops. Extra stabilization of -1.2 kcal/mol was found for a GA middle
      pair when flanked by at least one non-pyrimidine-pyrimidine loop-terminal pair. A
      penalty of approximately 1 kcal/mol was found for loops with a single loop
      terminal GA pair that has a U 3' to the G of the GA pair. A revised model for
      predicting stabilities of 3 x 3 loops is derived by multiple linear regression.

PMID- 15461460
TI  - Cysteine-rich secretory protein 3 is a ligand of alpha1B-glycoprotein in human
      plasma.
AB  - Human cysteine-rich secretory protein 3 (CRISP-3; also known as SGP28) belongs to
      a family of closely related proteins found in mammals and reptiles. Some
      mammalian CRISPs are known to be involved in the process of reproduction, whereas
      some of the CRISPs from reptiles are neurotoxin-like substances found in lizard
      saliva or snake venom. Human CRISP-3 is present in exocrine secretions and in
      secretory granules of neutrophilic granulocytes and is believed to play a role in
      innate immunity. On the basis of the relatively high content of CRISP-3 in human
      plasma and the small size of the protein (28 kDa), we hypothesized that CRISP-3
      in plasma was bound to another component. This was supported by size-exclusion
      chromatography and immunoprecipitation of plasma proteins. The binding partner
      was identified by mass spectrometry as alpha(1)B-glycoprotein (A1BG), which is a
      known plasma protein of unknown function and a member of the immunoglobulin
      superfamily. We demonstrate that CRISP-3 is a specific and high-affinity ligand
      of A1BG with a dissociation constant in the nanomolar range as evidenced by
      surface plasmon resonance. The A1BG-CRISP-3 complex is noncovalent with a 1:1
      stoichiometry and is held together by strong electrostatic forces. Similar
      complexes have been described between toxins from snake venom and A1BG-like
      plasma proteins from opossum species. In these cases, complex formation inhibits
      the toxic effect of snake venom metalloproteinases or myotoxins and protects the
      animal from envenomation. We suggest that the A1BG-CRISP-3 complex displays a
      similar function in protecting the circulation from a potentially harmful effect
      of free CRISP-3.

PMID- 15461461
TI  - Aminobacter aminovorans NADH:flavin oxidoreductase His140: a highly conserved
      residue critical for NADH binding and utilization.
AB  - Homodimeric FRD(Aa) Class I is an NADH:flavin oxidoreductase from Aminobacter
      aminovorans. It is unusual because it contains an FMN cofactor but utilizes a
      sequential-ordered kinetic mechanism. Because little is known about NADH-specific
      flavin reductases in general and FRD(Aa) in particular, this study aimed to
      further explore FRD(Aa) by identifying the functionalities of a key residue. A
      sequence alignment of FRD(Aa) with several known and hypothetical flavoproteins
      in the same subfamily reveals within the flavin reductase active-site domain a
      conserved GDH motif, which is believed to be responsible for the enzyme and NADH
      interaction. Mutation of the His140 in this GDH motif to alanine reduced FRD(Aa)
      activity to <3%. An ultrafiltration assay and fluorescence quenching demonstrated
      that H140A FRD(Aa) binds FMN in the same 1:1 stoichiometric ratio as the wild
      type enzyme, but with slightly weakened affinity (K(d) = 0.9 microM). Anaerobic
      stopped-flow studies were carried out using both the native and mutated FRD(Aa).
      Similar to the native enzyme, H140A FRD(Aa) was also able to reduce the FMN
      cofactor by NADH although much less efficiently. Kinetic analysis of anaerobic
      reduction measurements indicated that the His140 residue of FRD(Aa) was essential
      to NADH binding, as well as important for the reduction of the FMN cofactor. For
      the native enzyme, the cofactor reduction was followed by at least one slower
      step in the catalytic pathway.

PMID- 15461462
TI  - Interstrand loops CD and EF act as pH-dependent gates to regulate fatty acid
      ligand binding in tear lipocalin.
AB  - Tear lipocalin (TL), a major component of human tears, shows pH-dependent
      endogenous ligand binding. The structural and conformational changes associated
      with ligand release in the pH range of 7.5-3.0 are monitored by circular
      dichroism spectroscopy and site-directed tryptophan fluorescence. In the
      transition from pH 7.5 to pH 5.5, the ligand affinity for 16-(9
      anthroyloxy)palmitic acid (16AP) and 8-anilino-1-naphthalenesulfonic acid is
      reduced. At pH 4.0 these ligands no longer bind within the TL calyx. From pH 7.3
      to pH 3.0, the residues on loops CD and EF, which overhang the calyx entrance,
      show reduced accessibility to acrylamide. In addition resonance energy transfer
      is enhanced between residues on the two loops; the distance between the loops
      narrows. These findings suggest that apposition of the loops at low pH excludes
      the ligand from the intracavitary binding site. The conformational changes
      observed in transition from pH 7.3 to pH 3.0 for loops CD and EF are quite
      different. The CD loop shows less population reshuffling than the EF loop with an
      acidic environment, probably because backbone motion is restrained by the
      adjacent disulfide bond. The Trp fluorescence wavelength maximum (lambda(max))
      reflects internal electrostatic interactions for positions on loops CD and EF.
      The titration curves of lambda(max) for mutants on the EF loop fit the Hendersen
      Hasselbalch equation for two apparent pK(a) values, while the CD loop positions
      fit satisfactorily with one pK(a) value. Midpoints of transition for the binding
      affinity of TL tryptophan mutants to 16AP occur at pH 5.5-6.1. Replacement of
      each amino acid on either loop by single tryptophan mutation does not disrupt the
      pH-dependent binding affinity to 16AP. Taken together the data suggest that pH
      driven ligand release involves ionization changes in several titratable residues
      associated with CD and EF loop apposition and occlusion of the calyx.

PMID- 15461463
TI  - Dependence of tyrosine oxidation in highly oxidizing bacterial reaction centers
      on pH and free-energy difference.
AB  - The pH and temperature dependences of tyrosine oxidation were measured in
      reaction centers from mutants of Rhodobacter sphaeroides containing a tyrosine
      residue near a highly oxidizing bacteriochlorophyll dimer. Under continuous
      illumination, a rapid increase in the absorption change at 420 nm was observed
      because of the formation of a charge-separated state involving the oxidized dimer
      and reduced primary quinone, followed by a slow absorption decrease attributed to
      tyrosine oxidation. Both the amplitude and rate of the slow absorption change
      showed a pH dependency, indicating that, at low pH, the rate of tyrosine
      oxidation is limited by the transfer of the phenolic proton to a nearby base.
      Below 17 degrees C, the rate of the slow absorption change had a strong
      exponential dependence on the temperature, indicating a high activation energy.
      At higher pH and temperature, the overall rate of tyrosyl formation appears to be
      limited by a proposed conformational change in the reaction center that is also
      observed in reaction centers that do not undergo tyrosine oxidation. The yield of
      tyrosyl formation measured using electron paramagnetic resonance spectroscopy
      decreased significantly at 4 degrees C compared to 20 degrees C and was lower at
      both temperatures in mutants expected to have a slightly smaller driving force
      for tyrosyl formation.

PMID- 15461464
TI  - Protein/lipid interaction in the bacterial photosynthetic reaction center:
      phosphatidylcholine and phosphatidylglycerol modify the free energy levels of the
      quinones.
AB  - The role of characteristic phospholipids of native membranes, phosphatidylcholine
      (PC), phosphatidylglycerol (PG), and cardiolipin (CL), was studied in the
      energetics of the acceptor quinone side in photosynthetic reaction centers of
      Rhodobacter sphaeroides. The rates of the first, k(AB)(1), and the second,
      k(AB)(2), electron transfer and that of the charge recombination, k(BP), the free
      energy levels of Q(A)(-)Q(B) and Q(A)Q(B)(-) states, and the changes of charge
      compensating protein relaxation were determined in RCs incorporated into
      artificial lipid bilayer membranes. In RCs embedded in the PC vesicle, k(AB)(1)
      and k(AB)(2) increased (from 3100 to 4100 s(-1) and from 740 to 3300 s(-1),
      respectively) and k(BP) decreased (from 0.77 to 0.39 s(-1)) compared to those
      measured in detergent at pH 7. In PG, k(AB)(1) and k(BP) decreased (to values of
      710 and 0.26 s(-1), respectively), while k(AB)(2) increased to 1506 s(-1) at pH
      7. The free energy between the Q(A)(-)Q(B) and Q(A)Q(B)(-) states decreased in PC
      and PG (DeltaG degrees (Q)A-(Q)B(-->)(Q)A(Q)B- = -76.9 and -88.5 meV,
      respectively) compared to that measured in detergent (-61.8 meV). The changes of
      the Q(A)/Q(A)(-) redox potential measured by delayed luminescence showed (1) a
      differential effect of lipids whether RC incorporated in micelles or vesicles,
      (2) an altered binding interaction between anionic lipids and RC, (3) a direct
      influence of PC and PG on the free energy levels of the primary and secondary
      quinones probably through the intraprotein hydrogen-bonding network, and (4) a
      larger increase of the Q(A)/Q(A)(-) free energy in PG than in PC both in
      detergent micelles and in single-component vesicles. On the basis of recent
      structural data, implications of the binding properties of phospholipids to RC
      and possible interactions between lipids and electron transfer components will be
      discussed.

PMID- 15461465
TI  - Exchangeability of mammalian DNA ligases between base excision repair pathways.
AB  - In mammalian cells, DNA ligase IIIalpha and DNA ligase I participate in the short
      and long-patch base excision repair pathways, respectively. Using an in vitro
      repair assay employing DNA ligase-depleted cell extracts and DNA substrates
      containing a single lesion repaired either through short-patch (regular abasic
      site) or long-patch (reduced abasic site) base excision repair pathways, we
      addressed the question whether DNA ligases are specific to each pathway or if
      they are exchangeable. We find that immunodepletion of DNA ligase I did not
      affect the short-patch repair pathway but blocked long-patch repair, suggesting
      that DNA ligase IIIalpha is not able to substitute DNA ligase I during long-patch
      repair. In contrast, immunodepletion of DNA ligase IIIalpha did not significantly
      affect either pathway. Moreover, repair of normal abasic sites in wild-type and X
      ray cross-complementing gene 1 (XRCC1)-DNA ligase IIIalpha-immunodepleted cell
      extracts involved similar proportions of short- and long-patch repair events.
      This suggests that DNA ligase I was able to efficiently substitute the XRCC1-DNA
      ligase IIIalpha complex during short-patch repair.

PMID- 15461466
TI  - Inhibition of protein kinase CK2 by condensed polyphenolic derivatives. An in
      vitro and in vivo study.
AB  - ATP site-directed inhibitors that can target individual kinases are powerful
      tools for use in signal transduction research, all the more so in the case of a
      pleiotropic, constitutively active protein kinase such as CK2, which is not
      turned on in response to specific stimuli. By screening a library of more than
      200 derivatives of natural polyphenolic compounds, we have identified 16
      molecules which inhibit CK2 with IC(50) values of <or=1 microM. They belong to
      the classes of anthraquinones (six compounds), xanthenones (two compounds),
      fluorenones (one compound), and coumarins (seven compounds), and their inhibitory
      potency correlates with the presence of nitro, amino, or halogen substituents at
      specific positions. Three of the most potent inhibitors, MNX (1,8-dihydroxy-4
      nitroxanthen-9-one), NBC (8-hydroxy-4-methyl-9-nitrobenzo[g]chromen-2-one), and
      DBC (3,8-dibromo-7-hydroxy-4-methylchromen-2-one), whose IC(50) values range
      between 0.13 and 0.36 microM, are quite specific toward CK2 within a panel of 33
      protein kinases tested. Treatment of Jurkat cells with these compounds promotes
      inhibition of endogenous CK2 and induction of apoptosis. A correlation is
      observed between their efficacy as CK2 inhibitors (as judged from IC(50) values)
      and their capacity to induce cell death (DC(50) values). Mutations of the unique
      CK2alpha residues Val66 and/or Ile174 to alanine have a detrimental effect on
      inhibition by these compounds with 16-67-fold increases in IC(50) values. The
      combined usage of these reagents can be exploited to gain information about
      cellular functions mediated by CK2.

PMID- 15461467
TI  - Single-molecule dynamics reveal an altered conformation for the autoinhibitory
      domain of plasma membrane Ca(2+)-ATPase bound to oxidatively modified calmodulin.
AB  - We used single-molecule polarization modulation methods to investigate the
      activation of the plasma membrane Ca(2+)-ATPase (PMCA) by oxidized calmodulin
      (CaM). Oxidative modification of methionine residues of CaM to their
      corresponding sulfoxides is known to inhibit the ability of CaM to activate PMCA.
      Single-molecule polarization methods were used to measure the orientational
      mobility of fluorescently labeled oxidized CaM bound to PMCA. We previously
      identified two distinct populations of PMCA-CaM complexes characterized by high
      and low orientational mobilities, with the low-mobility population appearing at a
      subsaturating Ca(2+) concentration [Osborn, K. D., et al. (2004) Biophys. J. 87,
      1892-1899]. We proposed that the high-mobility population corresponds to PMCA-CaM
      complexes with a dissociated (and mobile) autoinhibitory domain, whereas the low
      mobility population corresponds to PMCA-CaM complexes where the autoinhibitory
      domain is not dissociated and therefore the enzyme is not active. In the present
      experiments, performed with PMCA complexed with oxidatively modified CaM at a
      saturating Ca(2+) concentration, we found a large population of molecules with an
      orientationally immobile autoinhibitory domain. In contrast, native CaM bound to
      PMCA was characterized almost entirely by the more orientationally mobile
      population at a similar Ca(2+) concentration. The addition of 1 mM ATP to
      complexes of oxidized CaM with PMCA reduced but did not abolish the low-mobility
      population. These results indicate that the decline in the ability of oxidized
      CaM to activate PMCA results at least in part from its reduced ability to induce
      conformational changes in PMCA that result in dissociation of the autoinhibitory
      domain after CaM binding.

PMID- 15461469
TI  - High-resolution technique for fabricating environmentally sensitive hydrogel
      microstructures.

PMID- 15461468
TI  - Characterization of peptides corresponding to the seven transmembrane domains of
      human adenosine A2a receptor.
AB  - Human adenosine A(2)a receptor is a member of the G-protein-coupled receptor
      (GPCR) superfamily of seven-helix transmembrane (TM) proteins. To test general
      models for membrane-protein folding and to identify specific features of folding
      and assembly for this representative member of an important and poorly understood
      class of proteins, we synthesized peptides corresponding to its seven TM domains.
      We assessed the ability of the peptides to insert into micelles and vesicles and
      measured secondary structure for each peptide in aqueous and membrane-mimetic
      environments. CD spectra indicate that each of the seven TM peptides form
      thermally stable, independent alpha-helical structures in both micelles and
      vesicles. The helical content of the peptides depends on the nature of the
      membrane-mimetic environment. Four of the peptides (TM3, TM4, TM5, and TM7)
      exhibit very high-helical structure, near the predicted maximum for their TM
      segments. The TM1 peptide also adopts relatively high alpha-helical structures.
      In contrast, two of peptides, TM2 and TM6, display low alpha helicity. Similarly,
      the ability of the peptides to insert into membrane-mimetic environments, assayed
      by intrinsic tryptophan fluorescence and fluorescence quenching, varied markedly.
      Most peptides exhibit higher alpha helicity in anionic sodium dodecyl sulfate
      than in neutral dodecyl-beta-D-maltoside micelles, and TM2 was disordered in
      zwiterionic DMPC but was alpha-helical in negatively charged DMPC/DMPG vesicles.
      These findings strongly suggest that electrostatic interactions between lipids
      and peptides control the insertion of the peptides and may be involved in
      membrane-protein-folding events. The measured helical content of these TM domains
      does not correlate with the predicted helicity based on amino acid sequence,
      pointing out that, while hydrophobic interactions can be a major determinant for
      folding of TM peptides, other factors, such as electrostatic interactions or
      helix-helix interactions, may play significant roles for specific TM domains. Our
      results represent a comprehensive analysis of helical propensities for a human
      GPCR and support models for membrane-protein folding in which interactions
      between TM domains are required for proper insertion and folding of some TM helix
      domains. The tendency of some peptides to self-associate, especially in aqueous
      environments, underscores the need to prevent improper interactions during
      folding and refolding of membrane proteins in vivo and in vitro.

PMID- 15461470
TI  - Electric-field-induced layer-by-layer fabrication of second-order nonlinear
      optical films with high thermal stability.

PMID- 15461471
TI  - Tuning intermolecular interactions in a rodlike polymer assembled at surfaces and
      in solution.
AB  - The isolation of single polyelectrolyte chains of water-soluble
      poly(isocyanodipeptide)s (PICs) bearing carboxylic acid terminated side chains
      occurring both at surfaces and in solution was accomplished by reducing the
      intermolecular interactions through complexation with cations or positively
      charged surfactants. Scanning force microscopy and viscosity analyses revealed
      that this method allows to tune the conformation of the macromolecule, which is
      of importance for tailoring the physicochemical properties of the material. This
      is particularly significant for the use of these polymer chains as seed for
      biomineralization processes.

PMID- 15461472
TI  - Probing the hydration of lipid bilayers using a solvent isotope effect on
      phospholipid mixing.
AB  - Nearest-neighbor recognition experiments, which have been carried out using
      exchangeable dimers derived from 1,2-dimyristoyl-sn-glycero-3
      phosphoethanolamine, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine,and 1
      palmitoyl-2-oleoyl-sn-glycerophosphoethanolamine, indicate that replacement of
      H2O by D2O can significantly influence phospholipid mixing, but only in bilayers
      that are saturated and devoid of cholesterol. These findings, together with those
      of previous electron spin resonance spin-labeling studies,indicate that mammalian
      membranes, which are rich in cholesterol and unsaturated phospholipids, are ideal
      hydrophobic barriers.

PMID- 15461473
TI  - Protein deformation of lipid hybrid bilayer membranes studied by sum frequency
      generation vibrational spectroscopy.
AB  - Structural deformations of lipid hybrid bilayer membranes induced by signal
      peptideless (SPL) proteins have been studied for the first time using the
      inherently surface specific nonlinear optical technique of sum frequency
      generation vibrational spectroscopy. Specifically, deformations of 1,2
      distearoylphosphatidylglycerol(DSPG) membranes induced by interaction with FGF-1,
      a SPL protein which is released asa function of cellular stress through a
      nonclassical pathway, have been investigated. FGF-1 was found to induce lipid
      alkyl chain deformations in previously highly ordered DSPG membranes at the
      extremely low concentration of 1 nM at 60 degrees C. The deformation process was
      shown to exhibit a degree of reversibility upon removal of the protein by rinsing
      with buffer solution.

PMID- 15461474
TI  - Monitoring the simultaneous ostwald ripening and solubilization of emulsions.
AB  - The simultaneous Ostwald ripening of an emulsion and the solubilization of its
      oil droplets by added micellar surfactant solutions are monitored by measurements
      of time-averaged scattered intensities. A simple computer simulation model for
      the interpretation of the measurements is presented. Experimental data are
      analyzed with this model using one single parameter: an effective ratio of oil to
      surfactant molecules involved in the withdrawal of oil from the Ostwald ripening
      process by the added micelles. The fitted value of this parameter appears to be
      more than twice the one that can be predicted from the equilibrium solubilization
      of oil by the surfactant micelles, indicating that more oil is involved in the
      nonequilibrium exchange of oil and surfactant between micelles and droplets.

PMID- 15461475
TI  - Effects of organic solvents on the scission energy of rodlike micelles.
AB  - The linear viscoelastic response of erucyl bis(hydroxyethyl) methylammonium
      chloride with added KCl has been studied as a function of temperature and
      nonpolar solvent addition. The plateau modulus is independent of temperature from
      25 to 40 degrees C, in contrast to previous studies with salicylate counterions
      that showed a plateau modulus increasing with temperature over this range. The
      average micelle length, L, predicted by the model of Cates, depends
      experimentally on Escis/kBT, where Escis is the scission energy of the chain and
      kBT is the Boltzmann constant times the absolute temperature. With ethanol
      addition, the calculated average contour length, L, decreases by a factor of 4 as
      ethanol concentration varies from 0 to 1.3 M. This corresponds to an apparent
      energy for scission, Escis, decrease from 81 +/- 8 to 74 +/- 7 kJ/mol. On the
      other hand, only 80 mM of hexane is required to cause a decrease in Escis to the
      same level, and for hexane addition levels above 70 mM a disruption in the
      plateau modulus indicates the disruption of the rodlike structure. The
      correspondence between the effect of temperature and the effect of solvent
      addition allows the development of "solvent/temperature" superposition rules to
      predict the rheology of these viscoelastic fluids at elevated temperatures.

PMID- 15461476
TI  - A neutron scattering study of the structure and water partitioning of selectively
      deuterated copolymer micelles.
AB  - We present a scattering study of a selectively deuterated micelle-forming diblock
      copolymer. The copolymer comprises a partially deuterated polystyrene (d,h-PS)
      block and an imidazolium-functionalized PS (IL) block. In toluene solutions, the
      copolymers assemble into elongated micelles where the IL block forms the micelle
      core. Through dynamic light scattering (DLS) measurements, we obtain the overall
      size of the micelles. In our small-angle neutron scattering (SANS) studies, we
      use contrast matching to characterize the IL core and the PS shell of the
      micelles independently. The PS block forming the micelle shell exhibits either a
      starlike or brushlike conformation depending upon the size of the core to which
      it is tethered. We find the IL block to be in an extended conformation, driving
      the formation of slightly elongated and relatively stiff micelle cores. The
      elongated micelle core cross-sectional radius and length depend linearly on the
      length of the IL block. We find that the micelles can sequester a few water
      molecules for each IL repeat unit; the addition of water slightly increases the
      cross section of the elongated micelles.

PMID- 15461477
TI  - Complexation between dodecyl sulfate surfactant and zein protein in solution.
AB  - Interactions between sodium dodecyl sulfate and zein protein, a model system for
      the understanding of the effect of surfactants on skin, were investigated using a
      range of techniques involving UV-vis spectroscopy, TOC (total organic carbon
      analysis), electrophoresis, and static and dynamic light scattering. Zein protein
      was solubilized by SDS. The adsorption of SDS onto insoluble protein fraction
      caused the zeta potential of the complex to become more negative. From these
      values, we calculated the Gibbs energy of absorption, which decreases when the
      SDS concentration is raised. Finally the structure of the complex, based on the
      analysis by static and dynamic light scattering, is proposed to be rod like.

PMID- 15461478
TI  - Synthesis and characterization of novel pH-responsive microgels based on tertiary
      amine methacrylates.
AB  - Emulsion polymerization of 2-(diethylamino)ethyl methacrylate (DEA) in the
      presence of a bifunctional cross-linker at pH 8-9 afforded novel pH-responsive
      microgels of 250-700 nm diameter. Both batch and semicontinuous syntheses were
      explored using thermal and redox initiators. Various strategies were evaluated
      for achieving colloidal stability, including charge stabilization, surfactant
      stabilization, and steric stabilization. The latter proved to be the most
      convenient and effective, and three types of well-defined reactive macromonomers
      were examined, namely, monomethoxy-capped poly(ethylene glycol) methacrylate
      (PEGMA), styrene-capped poly[2-(dimethylamino)ethyl methacrylate] (PDMA50-St),
      and partially quaternized styrene-capped poly[2-(dimethylamino)ethyl
      methacrylate] (10qPDMA50-St). The resulting microgels were pH-responsive, as
      expected. Dynamic light scattering and 1H NMR studies confirmed that reversible
      swelling occurred at low pH due to protonation of the tertiary amine groups on
      the DEA residues. The critical pH for this latex-to-microgel transition was
      around pH 6.5-7.0, which corresponds approximately to the known pKa of 7.0-7.3
      for linear PDEA homopolymer. The microgel particles were further characterized by
      electron microscopy and aqueous electrophoresis studies. Their swelling and
      deswelling kinetics were investigated by turbidimetry. The PDEA-based microgels
      were compared to poly[2-(diisopropylamino)ethyl methacrylate] (PDPA) microgels
      prepared with identical macromonomer stabilizers. These PDPA-based microgels had
      a lower critical swelling pH of around pH 5.0-5.5, which correlates with the
      lower pKa of PDPA homopolymer. In addition, the kinetics of swelling for the PDPA
      microgels was somewhat slower than that observed for PDEA microgels; presumably
      this is related to the greater hydrophobic character of the former particles.

PMID- 15461479
TI  - Influence of natural organic matter and ionic composition on the kinetics and
      structure of hematite colloid aggregation: implications to iron depletion in
      estuaries.
AB  - The stability and aggregation behavior of iron oxide colloids in natural waters
      play an important role in controlling the fate, transport, and bioavailability of
      trace metals. Time-resolved dynamic light scattering experiments were carried out
      in a study of the aggregation kinetics and aggregate structure of natural organic
      matter (NOM) coated hematite colloids and bare hematite colloids. The aggregation
      behavior was examined over a range of solution chemistries, by adjusting the
      concentration of the supporting electrolyte-NaCl, CaCl2, or simulated seawater.
      With the solution pH adjusted so that NOM-coated and bare hematite colloids were
      at the same zeta potential, we observed a significant difference in colloid
      stability which results from the stability imparted to the colloids by the
      adsorbed NOM macromolecules. This enhanced stability of NOM-coated hematite
      colloids was not observed with CaCl2. Aggregate form expressed as fractal
      dimension was determined for both NOM-coated and bare hematite aggregates in both
      NaCl and CaCl2. The fractal dimensions of aggregates formed in the diffusion
      limited regime indicate slightly more loosely packed aggregates for bare hematite
      than theory predicts. For NOM-coated hematite, a small decrease in fractal
      dimension was observed when the solution composition changed from NaCl to CaCl2.
      For systems in the reaction-limited regime, the measured fractal dimensions
      agreed with those in the literature. Colloid aggregation was also studied in
      synthetic seawater, a mixed cation system to simulate estuarine mixing. Those
      results describe the important phenomena of iron oxide aggregation and
      sedimentation in estuaries. When compared to field data from the Mullica Estuary,
      U.S.A., it is shown that collision efficiency is a good predictor of the iron
      removal in this natural system.

PMID- 15461480
TI  - Stability of suspensions, emulsions, and foams studied by a novel automated
      analyzer.
AB  - The stability of dilute and concentrated dispersions (suspensions, emulsions, and
      foams) has been studied by a newly developed automated dispersion stability
      analyzer, DiStA 24. The analyzer operates by taking consecutive images of the
      samples studied and analyzing them by a personal computer (PC). As a result, the
      vertical profile of light scattered from each sample is obtained, recorded, and
      analyzed at time intervals preset by the computer software. In this way, the
      destructive processes in dispersions (sedimentation, creaming, and coalescence)
      can be detected well before it is possible by the naked eye and monitored
      automatically in the temperature range 0-50 degrees C. The new analyzer differs
      from the existing instruments by its simplicity and high productivity, allowing
      24 samples to be measured simultaneously.

PMID- 15461481
TI  - Salt effect on the complex formation between cationic gemini surfactant and
      anionic polyelectrolyte in aqueous solution.
AB  - Salt effect on the interaction of anionic polyelectrolyte sodium
      carboxymethylcellulose (NaCMC) with cationic gemini surfactant hexamethylene-1,6
      bis(dodecyldimethylammonium bromide) [C12H25(CH3)2N(CH2)6N(CH3)2C12H25]Br2
      (C12C6C12Br2) has been investigated using turbidimetric titration, steady-state
      fluorescence, and mobility measurement. It is found that the critical aggregation
      concentration(cac) for C12C6C12Br2/NaCMC complexes depends little on addition of
      sodium bromide (NaBr). However, in the presence of nonionic surfactant Triton X
      100 (TX100), the critical ionic surfactant mole fraction for the onset of complex
      formation (Yc) increases markedly with increasing NaBr concentration. These salt
      effects are supposed as the overall result from competition between the increase
      of interaction and the screening of interaction. The increase of interaction is
      referred to as the effect that the larger micelle with higher surface charge
      density induced by salt has a stronger interaction with oppositely charged
      polyelectrolyte. The screening of interaction is referred to as the salt
      screening of electrostatic attraction between the polymer chain and the
      surfactant. For complex formation between C12C6C12Br2 and NaCMC, the increase of
      interaction probably compensates the screening of interaction, leading to
      constant cac values at different salt concentrations. For complex formation
      between the C12C6C12Br2/TX100 mixed micelle and NaCMC, the screening of
      interaction probably plays a dominant role, leading to higher suppression of
      electrostatic binding of micelles to polyelectrolyte.

PMID- 15461482
TI  - Mixed self-assembly of poly(ethylene oxide)-b-poly(epsilon-caprolactone)
      copolymers and sodium dodecyl sulfate in aqueous solution.
AB  - Interaction of amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone)
      copolymers with anionic sodium dodecyl sulfate (SDS) has been investigated in
      aqueous solution. Formation of mixed micelles has been confirmed by surface
      tension measurements, whereas the influence of the surfactant on the copolymer
      self-assembling has been studied by measurement of the 1H NMR self-diffusion
      coefficients and by small-angle neutron scattering. As a rule, the surfactant
      decreases the heterogeneity of the micellar structures formed by the copolymer in
      water. Moreover, increasing the content of SDS results in the increasingly more
      important extension of the poly(ethylene oxide) (PEO) corona chains and the
      copolymer micelle deaggregation. The stability of the micelles against SDS
      increases with the length of the hydrophobic block. Preliminary two-dimensional
      NMR measurements with nuclear Overhauser enhancement have confirmed the spatial
      vicinity between SDS and the constitutive blocks of the copolymer.

PMID- 15461483
TI  - Effect of N-glycinylmaleamic acid on microstructural characteristics and
      solubilization properties of sodium dodecyl sulfate micellar assemblies.
AB  - The cosurfactant activity of N-glycinylmaleamic acid (NGMA) in sodium dodecyl
      sulfate (SDS) micelles has been demonstrated. The complementary techniques of
      electron spin resonance (ESR) and fluorescence spectroscopy have been used to
      draw information on hydration index (H), microviscosity (eta), and aggregation
      number (N) of micellar assemblies. The estimate of the critical micelle
      concentration of SDS in the presence of NGMA suggests a synergistic effect of
      NGMA. The enhanced solubilization of butyl propionate in the presence of NGMA in
      SDS micelles is explained on the basis of availability of larger interfacial area
      calculated from a simple spherical geometric model, combined with a low
      hydrophilicity index as estimated from ESR. Thus, addition of NGMA contributes to
      an increase of about 50% in ratio of area of polar shell (AP)/volume of hydration
      (Vh) ratio. The decrease in H accompanied by a decrease in eta with the
      incorporation of butyl propionate probably arises from solubilization of a butyl
      component inside the core with the adsorption of propionate ester on the
      interface.

PMID- 15461484
TI  - Two-phase channel structures based on alpha-cyclodextrin-polyethylene glycol
      inclusion complexes.
AB  - Wide-angle X-ray scattering observations of alpha-cyclodextrin (CD)-poly(ethylene
      glycol) (PEG) inclusion complexes (ICs) have shown for the first time that two
      crystalline columnar modifications (forms I and II) are produced in the process
      of their formation. This was made possible by precise azimuthal X-ray diffraction
      scanning of oriented IC samples. Form I is characterized by CDs threaded onto PEG
      chains and arranged along channels in the order head-to-head/tail-to-tail, while
      form II is formed by unbound CDs also arranged into columns in a head-to-tail and
      also possibly a head-to-head/tail-to-tail manner, probably as a result of
      template crystallization on the form I IC crystals. It was shown that similar
      structural peculiarities are inherent for channel structures based on ICs
      obtained with PEG with a wide range of molecular weights (MWs). The
      characteristic feature of ICs based on PEG, especially with MW > 8000, is the
      presence of unbound polymer in the composition of the complex. The amount of
      unbound PEG was shown to rise with increasing MW of PEG, resulting in greater
      imperfections in the IC crystalline structure. The polyblock structure of ICs
      based on alpha-CD and PEG was therefore proposed.

PMID- 15461485
TI  - Interfacial micellar structures from novel amphiphilic star polymers.
AB  - An amphiphilic heteroarm star polymer containing 12 alternating
      hydrophobic/hydrophilic arms of polystyrene (PS) and poly(acrylic acid) (PAA)
      connected to a well-defined rigid aromatic core was studied at the air-water and
      the air-solid interfaces. At the air-water interface, the molecules spontaneously
      form pancakelike micellar aggregates which measure up to several microns in
      diameter and 5 nm in thickness. Upon reduction of the surface area per molecule
      to 7 nm2, the two-dimensional micelles merged into a dense monolayer. We suggest
      that confined phase separation of dissimilar polymer arms occurred upon their
      segregation on the opposite sides of the rigid disklike aromatic core, forcing
      the rigid cores to adopt a face-on orientation with respect to the interface.
      Upon transfer onto solid supports the PS chains face the air-film interface
      making it completely hydrophobic, and the PAA chains were found to collapse and
      form a thin flattened underlayer. This study points toward new strategies to
      create large 2D microstructures with facial amphiphilicity and suggests a
      profound influence of star molecular architecture on the self-assembly of
      amphiphiles at the air-water interface.

PMID- 15461486
TI  - Imaging forster resonance energy transfer measurements of transmembrane helix
      interactions in lipid bilayers on a solid support.
AB  - We utilize supported lipid/protein bilayers to probe the dimerization of
      transmembrane (TM) helices in a membrane environment. The bilayers are formed by
      incubating substrates with liposomes containing the proteins, and are
      characterized using fluorescence recovery after photobleaching and imaging
      Forster resonance energy transfer (FRET). We show that the FRET signal, as a
      measure of TM helix dimerization, is the same in suspended liposomes and in
      surface-supported bilayers. This work is the first step toward the development of
      a new tool for probing the association of TM helices in lipid bilayers.

PMID- 15461487
TI  - Effect of the hydrophilic size on the structural phases of aqueous nonionic
      gemini surfactant solutions.
AB  - Aggregate structures of aqueous nonionic Gemini surfactant solutions,
      alpha,alpha'-[2,4,7,9-tetramethyl-5-decyne-4,7-diyl]bis[omega-hydroxyl
      polyoxyethylene] with three different length polyoxyethylenes (i.e., 10, 20, and
      30 ethylene oxide monomers, denoted from now on as S-10, S-20, and S-30,
      respectively), are investigated using small angle neutron scattering, dynamic
      light scattering, and fluorescence spectroscopy. For S-10 at low surfactant
      concentrations (Cs < 0.9 wt %), large "clusters", with an average hydrodynamic
      radius (RH) > 40 nm, are found to coexist with monomers. At intermediate Cs (0.9
      < Cs < 2 wt %), some clusters break down forming micelles, with an (RH)
      approximately 2-3 nm, while the remaining clusters coexist with micelles.
      Increasing Cs further (>2 wt %) results in a pure micellar phase with little or
      no clusters present. S-20 and S-30 mixtures, on the other hand, differ from S-10
      in that irrespective of surfactant concentration, large clusters and small
      monomers/dimers are found to coexist, while there is no direct evidence for the
      presence of micelles.

PMID- 15461488
TI  - Crystallization of silver stearate from sodium stearate dispersions.
AB  - Silver carboxylates, the common silver source used for photothermographic imaging
      materials, are normally obtained from the reaction between sodium soap (e.g.,
      sodium stearate) and silver nitrate. They form platelet-like crystals with a
      lamellar structure in water at room temperature. Light microscopy investigations
      reveal that the formation of silver stearate (AgSt) crystals follows a diffusion
      controlled mechanism. The reaction between the sodium soap and silver nitrate
      preferentially occurs in solution rather than on the soap fiber solid interface.
      Cryogenic transmission electron microscopy, together with an on-the-grid reaction
      technique, provides a useful tool to directly image silver stearate
      microstructures at the initial stages of AgSt precipitation. The AgSt reaction
      product first forms particles about 5 nm in size, which is similar to the d
      spacing of final AgSt crystals. Those particles aggregate to produce larger and
      loosely packed embryonic crystals, the precursors to the ultimate silver stearate
      crystals.

PMID- 15461489
TI  - Changing surface hydro- and oleophobicity with resorcinarene multilayers-a simple
      water/oil proofing process.
AB  - Resorcinarenes (resorcinol-aldehyde tetramers) of appropriate structures have
      been shown to change the hydro- and oleophilicities of a variety of surfaces. The
      phenomenon results from attachment of the rim of the bowl-like molecules to
      hydrophilic surfaces. Hydrophobic (alkyl) and oleophobic (perfluoro alkyl) "legs"
      attached to the bowls then determine the immediate surface property. Amounts
      required to modify surfaces are only between 2 and 10 mg m(-2) treated, and there
      is evidence of multilayer formation. Penetration of surfaces by a variety of
      liquids has been studied and cannot easily be understood as a function of
      density, viscosity, or surface tension.

PMID- 15461490
TI  - Patterning multiple aligned self-assembled monolayers using light.
AB  - This work describes a method for patterning a gold substrate with multiple,
      aligned self-assembled monolayers (SAMs) using light at different wavelengths. It
      describes the synthesis and characterization of an alkanethiolate SAM that is
      photosensitive to light at both 220 and 365 nm. A photomask acts as an area
      selective filter for light at 220 and 365 nm, and a single set of exposures at
      these two wavelengths through one photomask, without steps of alignment between
      the exposures, can produce three aligned SAMs on one gold substrate. We
      demonstrate the versatility of this method of photopatterning by modifying
      individual aligned SAMs chemically to produce surfaces having different
      properties. We characterize the modified SAMs using immunolabeling, matrix
      assisted laser desorption/ionization time-of-flight mass spectroscopy, and
      surface plasmon resonance spectroscopy. We also describe the patterning of two
      aligned SAMs that resist the adsorption of proteins and a third region that does
      not resist the adsorption of proteins. The ability to produce multiple, aligned
      patterns of SAMs in a single step, without alignment of photomasks in separate
      steps, increases the versatility of SAMs for studying a range of physical
      phenomena.

PMID- 15461491
TI  - Influence of the foundation layer on the layer-by-layer assembly of poly-L-lysine
      and poly(styrenesulfonate) and its usage in the fabrication of 3D microscale
      features.
AB  - The layer-by-layer (LBL) assembly of a polypeptide, poly-L-lysine (PLL), with
      poly(styrenesulfonate) sodium salt (PSS) on flat template-stripped gold (TSG)
      surfaces precoated with a self-assembled monolayer of alkanethiols terminated
      with positive (pyridinium), negative (carboxylic acid), and neutral
      [hexa(ethylene glycol)] groups is investigated. Both the topography and the rate
      of film thickness growth are found to be strongly dependent on the initial
      surface foundation layer. LBL assembly of PLL and PSS on patterned TSG surfaces
      produced by micro contact printing leads to structurally distinct microscale
      features, including pillars, ridges, and wells, whose height can be controlled
      with nanometer precision.

PMID- 15461492
TI  - Effects of template and precursor chemistry on structure and properties of
      mesoporous TiO2 thin films.
AB  - Mesoporous TiO2 thin films were synthesized by sol-gel processing using an
      aqueous-based, inexpensive, and environmentally friendly precursor and cationic
      surfactants as templates under mild reaction conditions. The films were prepared
      by spin-coating on glass substrates followed by calcination to remove the
      surfactant. N2 sorption, X-ray diffraction, and transmission electron microscopy
      were used to characterize the porosity, pore size, and pore structure before and
      after calcination. Films were found to have wormlike pore structures after
      calcination and surface areas on the order of 200 m2/g. These results show that
      the mesostructure and porosity of the thin films can be controlled by the
      surfactant template chemistry such as surfactant/Ti ratio, pH, and rate of
      solvent evaporation.

PMID- 15461493
TI  - Metachromatic effects and photodegradation of basic blue on nanocrystalline
      titania films.
AB  - Titania nanocrystalline films have been deposited on solid substrates by a sol
      gel procedure carried out in Triton X-100 reverse micelles. When the dye Basic
      Blue is adsorbed on these films, it demonstrates a strong metachromatic effect;
      that is, it aggregates, resulting in a blue shift of its absorption spectrum.
      Metachromasy in this system is related to the hydrophilicity of the film surface
      and to the humidity of the film environment. Films composed of 67% titania and
      33% silica gave an intense and reversible metachromatic effect that can be
      exploited to make a handy humidity sensor. Photodegradation of Basic Blue on
      titania films is faster in humid environments than in dry environments, and this
      goes in parallel with metachromatic effects.

PMID- 15461494
TI  - Molecular modeling of alkyl monolayers on the Si(100)-2 x 1 surface.
AB  - Molecular modeling was used to simulate various surfaces derived from the
      addition of 1-alkenes and 1-alkynes to Si=Si dimers on the Si(100)-2 x 1 surface.
      The primary aim was to better understand the interactions between adsorbates on
      the surface and distortions of the underlying silicon crystal due to
      functionalization. Random addition of ethylene and acetylene was used to
      determine how the addition of an adduct molecule affects subsequent additions for
      coverages up to one molecule per silicon dimer, that is, 100% coverage.
      Randomization subdues the effect that the relative positions of the adsorbates
      have on the enthalpy of the system. For ethylene and acetylene, the enthalpy of
      reaction changes less than 3 and 5 kcal/mol, respectively, from the first reacted
      species up to 100% coverage. As a result, a (near-)complete coverage is
      predicted, which is in line with experimental data. When 1-alkenes and 1-alkynes
      add by [2 + 2] addition, the hydrocarbon chains interact differently depending on
      the direction they project from the surface. These effects were investigated for
      four-carbon chains: 1-butene and 1-butyne. As expected, the chains that would
      otherwise intersect bend to avoid each other, raising the enthalpy of the system.
      For alkyl chains longer than four carbons, the chains are able to reorient
      themselves in a favorable manner, thus, resulting in a steady reduction in
      reaction enthalpy of about 2 kcal/mol for each additional methylene unit.

PMID- 15461495
TI  - Parameters influencing the templated growth of colloidal crystals on chemically
      patterned surfaces.
AB  - The influence of various experimental parameters on the vertical deposition and
      structure formation of colloidal crystals on chemically patterned surfaces, with
      hydrophilic and hydrophobic areas, was investigated. The pattern dimensions range
      from about 4 to 400 microm, which is much larger than the individual particle
      size (255 nm), to control the microscopic crystal shape rather than influencing
      the crystal lattice geometry (as achieved in colloidal epitaxy). The deposition
      resolution and selectivity were tested by varying the particle concentration in
      the suspension, the substrate withdrawing speed, pattern size and orientation,
      and wetting contrast between the hydrophilic and hydrophobic regions. The
      evolution of colloidal crystal thickness with respect to the pattern dimensions
      and deposition parameters was further studied. Our results show that the pattern
      size has a rather strong influence on the deposited number of colloid layers and
      on the crystal quality. Better results are obtained when the lines of a stripe
      pattern are oriented parallel to the withdrawing direction rather than
      perpendicular. The deposition resolution (defined as the minimum feature size on
      which particles can be deposited) depends on the wetting contrast and increases
      with lower average hydrophobicity of the substrate.

PMID- 15461496
TI  - Formation of a supramolecular gel between alpha-cyclodextrin and free and
      adsorbed PEO on the surface of colloidal silica: effect of temperature, solvent,
      and particle size.
AB  - Aqueous solutions of alpha-cyclodextrin (alpha-CD) complex spontaneously with
      poly(ethylene oxide) (PEO), forming a supramolecular structure known as
      pseudopolyrotaxane. We have studied the formation of the complex obtained from
      the threading of alpha-CD onto PEO, both free in solution and adsorbed on
      colloidal silica. The kinetics of the reaction were studied by gravimetric
      methods and determined as a function of temperature and solvent composition for
      the PEO free in solution. PEO was then adsorbed on the surface of colloidal
      silica particles, and the monomers were displaced by systematically varying the
      degree of complexation, the concentration of particles, and the molecular weight
      of the polymer. The effect of the size of the silica particles on the yield of
      the reaction was also studied. With the adsorbed PEO, the complexation was found
      to be partial and to take place from the tails of the polymer. The formation of a
      gel network containing silica at high degrees of complexation was observed. Small
      angle X-ray and neutron scattering experiments were performed to study the
      configuration of the polymeric chains and confirmed the partial desorption of the
      polymer from the surface of the silica upon complexation.

PMID- 15461497
TI  - CO2 adsorption over Si-MCM-41 materials having basic sites created by
      postmodification with La2O3.
AB  - Moderate basic sites could be created onto mesoporous Si-MCM-41 materials by
      postsynthesis modification with highly dispersed La2O3. The La2O3-modified MCM-41
      materials (designated here as LaM) have been characterized by Fourier transform
      infrared spectroscopy, temperature-programmed desorption, X-ray photoelectron
      spectroscopy, X-ray diffraction (XRD), and N2 adsorption/desorption and have been
      tested as model adsorbents for CO2 adsorption. XRD and N2 adsorption results
      showed that all LaM materials still maintained their uniform hexagonal mesoporous
      structure even after postsynthesis modification with La2O3 loading up to 20 wt %.
      Although the surface area, pore size, and pore volume of LaM materials decreased
      with increasing La2O3 loading, their capacity for CO2 storage could be
      significantly improved when La2O3 loading was increased from 0 to 10 wt %.
      Unidentate and bidentate carbonates have been identified by in situ FTIR as the
      two types of CO2 species adsorbed on LaM surface. The LaM material also possesses
      good thermal stability, allowing the model adsorbent to be regenerated at high
      temperature and recyclable.

PMID- 15461498
TI  - Electron scattering cross section on the surface of thin ag and au films induced
      by atomic deuterium adsorption.
AB  - The electron scattering cross section on the surface of thin silver and gold
      films induced by adsorption of atomic deuterium under conditions when a single
      adsorption state is formed was determined. Adsorption of atomic deuterium carried
      out at 78 K on sintered thin silver (gold) films deposited on Pyrex glass under
      ultrahigh vacuum conditions was studied measuring the resistance changes DeltaR
      "in situ". The adsorption runs performed at various exposures were followed by
      thermal desorption. This allowed establishment of a correlation between DeltaR
      and the uptake of the adsorbate. BET measurements were performed to determine the
      real area of the thin films and calculate the density of the adsorbate on their
      surface. It was found that in agreement with Wissmann's equation1 a linear
      dependence of DeltaR on the density of the adsorbate nads exists within a large
      interval of the population (nads < or = 1 x 10(15) D adatoms/cm2 on silver and 7
      x 10(14) D adatoms/cm2 on gold) available under our experimental conditions. On
      the basis of this equation the electron scattering cross section Aads induced by
      adsorption of atomic deuterium on sintered thin silver and gold films was
      calculated as reaching 4.75 x 10(-16) and 4.46 x 10(-16) cm2, respectively. A
      small isotope effect in the electron scattering cross section for adsorption of
      hydrogen on silver was observed: Aads = 5.48 x 10(-16) cm2.

PMID- 15461499
TI  - In situ deprotection and assembly of s-tritylalkanethiols on gold yields
      monolayers comparable to those prepared directly from alkanethiols.
AB  - In this paper we describe a systematic study comparing the properties of self
      assembled monolayers (SAMs) formed by in situ deprotection and assembly of S
      triphenylmethyl (trityl)- and thiolacetate-protected alkanethiols to those of
      SAMs formed from the parent alkanethiols. The two in situ deprotections were
      carried out in trifluoroacetic acid and THF/ammonium hydroxide, respectively.
      Monolayers of octadecanethiol (ODT) and the peptide-containing alkanethiol 3
      mercapto-N-n-pentadecylpropionamide (1ATC15) were assembled on gold using the two
      in situ methods and characterized by contact angle goniometry, X-ray
      photoelectron spectroscopy, polarization modulation infrared reflection
      absorption spectroscopy, and electrochemical characterization methods to assess
      how the monolayer properties compare to those of monolayers prepared by
      traditional methods. The results for the in situ deprotection of the trityl
      protected molecules demonstrate that this method can afford high-quality
      monolayers that are nearly indistinguishable from those prepared directly from
      alkanethiols. The quality of the monolayers prepared using this method is shown
      to depend on the solubility of the trityl-protected compound in trifluoroacetic
      acid. The results for the in situ deprotection of acetyl-ODT indicate this method
      yields low-quality monolayers that contain mixtures of adsorbates bound as
      thiolates and thiolacetates. In situ trityl deprotection is a useful approach for
      monolayer formation that greatly simplifies the purification, handling, and
      assembly of thiol-containing monolayer precursors.

PMID- 15461500
TI  - Effect of phloretin on the dipole potential of phosphatidylcholine,
      phosphatidylethanolamine, and phosphatidylglycerol monolayers.
AB  - The effect of phloretin on the potential of phosphatidylcholine (PC),
      phosphatidylethanolamine (PE,) and phosphatidylglycerol (PG) monolayers below and
      above the phase transition in mixtures of different PC/PE ratios with and without
      cholesterol of ester and ether phospholipids have been determined. The
      effectiveness of phloretin to decrease the dipole potential of monolayers in the
      fluid state is lessened by the moieties esterified to the phosphate group in the
      sequence choline > ethanolamine > glycerol. These effects on the dipole potential
      of monolayers are independent of the presence of carbonyls. In addition, in the
      gel state phloretin does not affect the dipole potential on
      dimyristoylphosphatidylethanolamine, although it is very pronounced in
      dimyristoylphosphatidylcholine. The changes of the dipole potential induced by
      phloretin were correlated with the packing of the lipids and with the formation
      of intermolecular hydrogen bonds between adjacent phospholipid molecules. These
      results may be indicative of the different distribution of polarized water around
      the phosphate groups imposed by the surrounding environment.

PMID- 15461501
TI  - Subcritical failure of soft acrylic adhesives under tensile stress.
AB  - The mechanisms of failure over time of a series of model acrylic pressure
      sensitive adhesives under a moderate level of stress has been investigated with a
      probe method. Two competing mechanisms of failure have been observed: a
      progressive nucleation of cavities under stress and the propagation of existing
      cavities at the interface between the probe and the adhesive layer. Homogeneous
      creep of the adhesive was never observed as the only failure mechanism. In
      situations where the resistance to crack propagation was good relative to the
      resistance to cavitation, extensive nucleation of cavities was observed until a
      material-dependent and stable value of stress was achieved. On the other hand in
      situations were the resistance to crack propagation was weak, propagation led
      invariably to a complete failure of the adhesive bond. In addition to the stress
      relaxation, the energy dissipation was studied allowing to distinguish the
      different adhesives even further. This allowed determination of the optimal
      amount of a comonomer (acrylic acid) that had to be added to improve the long
      term resistance of the adhesives under study. Further more we investigate the
      compliance of the confined adhesive layers and compare the obtained results to
      predictions from theoretical models.

PMID- 15461502
TI  - Adsorption of poly(vinyl alcohol) from water to a hydrophobic surface: effects of
      molecular weight, degree of hydrolysis, salt, and temperature.
AB  - The adsorption of poly(vinyl alcohol) (PVOH) from aqueous solutions to a silicon
      supported fluoroalkyl monolayer is described. Thickness, wettability, and
      roughness of adsorbed films are studied as a function of polymer molecular
      weight, degree of hydrolysis (from the precursor, poly(vinyl acetate)), polymer
      concentration, salt type and concentration, and temperature. The data suggest a
      two-stage process for adsorption of the polymer: physisorption due to a
      hydrophobic effect (decrease in interfacial free energy) and subsequent
      stabilization of the adsorbed layer due to crystallization of the polymer.
      Adsorption of lower-molecular-weight polymers results in thicker films than those
      prepared with a higher molecular weight; this is ascribed to better
      crystallization of more mobile short chains. Higher contents of unhydrolyzed
      acetate groups on the poly(vinyl alcohol) chain lead to thicker adsorbed films.
      Residual acetate groups partition to the outermost surface of the films and
      determine wettability. Salts, including sodium chloride and sodium sulfate,
      promote adsorption, which results in thicker films; at the same time, their
      presence over a wide concentration range leads to formation of rough coatings.
      Sodium thiocyanate has little effect on PVOH adsorption, only slightly reducing
      the thickness in a 2 M salt solution. Increased temperature promotes adsorption
      in the presence of salt, but has little effect on salt-free solutions. Evidently,
      higher temperatures favor adsorption but cause crystallization to be less
      thermodynamically favorable. These competing effects result in the smoothest
      coatings being formed in an intermediate temperature range.

PMID- 15461503
TI  - Effect of a modification site on the electron-transfer reaction of glucose
      oxidase hybrids modified with phenothiazine via a poly(ethylene oxide) spacer.
AB  - Glucose oxidase [GOx-(PT-PEONH2)] hybrids are synthesized by attaching
      phenothiazine (PT) groups to aspartic and glutamic acid residues on the enzyme
      surface via poly(ethylene oxide) (PEO) spacers of different molecular weights. A
      fast oxidation of FADH2/FADH by PT+ with the aid of the local motion of a
      hydrophilic, long, flexible PEO spacer is achieved for the GOx-(PT-PEONH2)
      hybrids and yields greater electron-transfer (ET) rates than that for GOx-(PTNH2)
      hybrids, in which the PT groups are directly bonded to the GOx surface. The ET
      rate of GOx-(PT-PEONH2) hybrids depends on the molecular weight of PT-PEONH2, and
      the maximum is obtained at a molecular weight of 3000. The ET rates of GOx
      hybrids are compared in terms of the location of the PT modification and the
      length and structure of the spacer chain connection of the PT mediator to a
      surface amino acid residue. Greater ET rates are obtained for the modification at
      aspartic and glutamic acid residues than for the lysine modification when the PT
      groups are bonded directly or via a short PEO spacer chain. In contrast, no
      advantage of aspartic and glutamic acid residues over lysine residues in
      generating a fast oxidation of FADH2/FADH by PT+ is observed for GOx hybrids in
      which the PT groups are attached via longer PEO spacers. The long PEO spacer is
      able to compensate the disadvantage of lysine residues locating far from the FAD
      center in GOx hybrids whose mediation reactions are based on the so-called wipe
      mechanism.

PMID- 15461504
TI  - Chemical surface modification of poly(p-xylylene) thin films.
AB  - Electrophilic aromatic substitution reactions were studied at poly(p-xylylene)
      (PPX) film surface-reaction medium interfaces. The extent of the reactions (depth
      of penetration and degree of substitution) was determined by the interaction of
      the polymer with the reaction solution. Reaction with chlorosulfonic acid to
      produce sulfonyl chloride and sulfone functionalities occurred readily in the
      bulk of PPX, and yields were sensitive to time and temperature. Confinement of
      this reaction to the PPX surface was achieved by controlling the concentration of
      the acid. Functionalization of PPX with N-methylol-2-chloroacetamide in sulfuric
      acid to produce the chloroamidomethylated derivative occurred in high yield and
      was confined to the surface region of PPX. Hydrolysis of the amide to generate
      aminomethylated PPX was assessed by XPS and a derivatization reaction. Friedel
      Crafts type chemistry (acylation and alkylation reactions) also produced
      functionalized surfaces, but with lower degrees of substitution than the other
      two reactions and was strictly surface-confined.

PMID- 15461505
TI  - Stabilization of phospholipid multilayers at the air-water interface by
      compression beyond the collapse: a BAM, PM-IRRAS, and molecular dynamics study.
AB  - Compression beyond the collapse of phospholipid monolayers on a modified Langmuir
      trough has revealed the formation of stable multilayers at the air-water
      interface. Those systems are relevant new models for studying the properties of
      biological membranes and for understanding the nature of interactions between
      membranes and peptides or proteins. The collapse of 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC), 1,2-di[cis-9-octadecenoyl]-sn-glycero-3-[phospho-l-serine]
      (DOPS), 1,2-di[cis-9-octadecenoyl]-sn-glycero-3-phosphocholine (DOPC), and 1,2
      di[cis-9-octadecenoyl]-sn-glycero-3-[phospho-1-rac-glycerol] (DOPG) monolayers
      has been investigated by isotherm measurements, Brewster angle microscopy (BAM),
      and polarization modulation infrared reflection-absorption spectroscopy (PM
      IRRAS). In the cases of DMPC and DOPS, the collapse of the monolayers revealed
      the formation of bilayer and trilayer structures, respectively. The DMPC bilayer
      stability has been analyzed also by a molecular dynamics study. The collapse of
      the DOPC and DOPG systems shows a different behavior, and the Brewster angle
      microscopy reveals the formation of luminous bundles, which can be interpreted as
      diving multilayers in the subphase.

PMID- 15461506
TI  - Fullerene adlayers on various single-crystal metal surfaces prepared by transfer
      from L films.
AB  - Fullerene adlayers prepared by the simple Langmuir-Blodgett (LB) method onto
      various well-defined single-crystal metal surfaces were investigated by in situ
      scanning tunneling microscopy (STM). The surface morphologies of fullerene
      adsorbed onto metal surfaces depended largely on the adsorbate-substrate
      interactions, which are governed by the types of surfaces. Too weak adsorption of
      C60 molecules onto iodine-modified Au(111) (I/Au(111)) allows surface migration
      of the molecules, and then, STM cannot visualize the C60 molecules. Stronger and
      appropriate adsorption onto bare Au(111) leads to highly ordered arrays
      relatively easily due to the limited surface migration of C60. On iodine-modified
      Pt(111) (I/Pt(111)) and bare Pt(111) surfaces, which have stronger adsorption,
      randomly adsorbed molecular adlayers were observed. Although C60 molecules on
      Au(111) were visualized as a featureless ball due to the maintenance of the rapid
      rotational motion (perturbation) of C60 on the surface at room temperature, those
      on I/Pt(111) revealed the intramolecular structures, thus indicating that the
      perturbation motion of molecules on the surface was prohibited.

PMID- 15461507
TI  - Nonlinear optical probe of biopolymer adsorption on colloidal particle surface:
      poly-L-lysine on polystyrene sulfate microspheres.
AB  - A nonlinear optical technique--second harmonic generation (SHG)--has been applied
      to characterize the adsorption of poly-L-lysine on micrometer size polystyrene
      particles, whose surface is covered with negatively charged sulfonate groups, in
      aqueous solutions. Adsorption behavior of the biopolymer with two chain lengths
      (14 and 75 amino acid units; PL14 and PL75) has been examined. Centrifugation
      experiments were also performed to support the adsorption measurements made using
      SHG. The adsorption free energies of the two polymers PL75 and PL14 are
      determined as -16.57 and -14.40 kcal/mol, respectively. The small difference in
      the adsorption free energies of the two chain lengths, however, leads to dramatic
      difference in the concentration needed for saturated surface coverage: nearly 50
      times higher concentration is needed for the smaller polymer. Under acidic
      colloidal conditions, polylysine is found to adsorb in a relatively flat
      conformation on the surface. The surface area that each polylysine molecule
      occupies is nearly 1 order of magnitude larger than the size of the molecule in
      its extended form. The low adsorption density is likely a result from Coulombic
      repulsion between the positive charges on the amino acid units of PL. The
      measurements demonstrate the utility of SHG as an efficient and sensitive
      experimental approach for measuring adsorption characteristics of
      bio/macromolecules on colloidal particles and define surface and colloidal
      conditions for achieving maximum surface coverage of a widely used biopolymer.

PMID- 15461509
TI  - Ozonation of naphthalenesulphonic acid in the aqueous phase in the presence of
      basic activated carbons.
AB  - The present study aimed to explore the possibility of increasing the purification
      efficacy of ozone in the removal of high-toxicity contaminants by using carbons
      of basic character and to analyze the mechanism involved in this process. These
      carbons were prepared by treating a commercial activated carbon (Witco, W) with
      ammonia (W-A), ammonium carbonate (W-C), or urea (W-U), under high pressure and
      temperature. The ammonia and carbonate treatments slightly increased the
      mesoporosity and, to a greater degree, the macroporosity of carbon W, whereas the
      urea treatment produced an increase in the porosity across the whole range of
      pore sizes. In addition, treatment of the activated carbon with these
      nitrogenating agents produced a marked change in the chemical nature of its
      surface. Thus, according to the pH of the point of zero charge (pHPZC) values
      obtained for each sample, carbon W was neutral (pHPZC = 7.12), but the treated
      carbons were basic, especially carbon W-U (pHPZC = 8.85). This basicity results
      from an increased concentration of basic oxygenated and nitrogenated surface
      functional groups, as confirmed by the results of elemental and XPS analyses. An
      increase in the degradation of 1,3,6-naphthalenetrisulfonic acid was observed
      when the activated carbon samples were added to the system. This degradation was
      especially enhanced in the presence of carbon W-U. The increased NTS degradation
      rate in the presence of the activated carbon is due to an increased concentration
      of highly reactive radicals in the system. When the catalytic activity of the
      activated carbon samples was related to their chemical and textural
      characteristics, it was found that: (i) The catalytic activity increased with an
      increase in the surface basicity. Interestingly, in the sample with greatest
      catalytic activity in NTS ozonation, carbon W-U, most of the nitrogenated surface
      groups introduced were pyrrol groups. These groups increase the electronic
      density of the basal plane of the activated carbon, thereby enhancing the
      reduction of ozone on the surface and the generation of highly reactive radicals
      in the system. (ii) The greater catalytic activity of carbon W-U may also be
      partly related to its greater surface area and higher volume of mesopores and
      macropores; these large pores facilitate access of the ozone to the surface
      active centers of the carbon, increasing its catalytic activity. The presence of
      the activated carbon samples during NTS ozonation also favored the removal of
      total organic carbon present in the solution, due to (a) transformation of
      organic matter into CO2 through the generation of highly reactive species
      catalyzed by the presence of the activated carbons (catalytic contribution) and
      (b) adsorption of NTS oxidation byproducts on the activated carbon (adsorptive
      contribution). The results obtained show that activated carbons treated with
      nitrogenating agents are very promising catalysts for application in the
      ozonation of aromatic compounds.

PMID- 15461508
TI  - Sacrificial adhesion promotion layers for copper metallization of device
      structures.
AB  - The adhesion of copper films to adjacent device layers including TiN, Ta, and TaN
      diffusion barriers is a crucial reliability issue for integrated circuits. We
      report that ultrathin layers of poly(acrylic acid) (PAA) prepared on barrier
      surfaces or on the native oxide of Si wafers dramatically increase the
      interfacial adhesion of Cu films deposited by the H2 assisted reduction of
      bis(2,2,7-trimethyloctane-3,5-dionato)copper in supercritical carbon dioxide.
      Similar improvements were achieved on Si wafers using a simple vapor phase
      exposure of the substrate to acrylic acid prior to metallization. The deposited
      films and the substrate/Cu interfaces were analyzed by X-ray photoelectron
      spectroscopy (XPS), electron microscopy, atomic force microscopy, and variable
      angle spectroscopic ellipsometry. No trace of the adhesion layer was detected at
      the interface, indicating it was sacrificial at the deposition conditions used.
      Moreover, the presence and subsequent decomposition of the PAA layer during
      deposition substantially reduced or eliminated metal oxides at the substrate
      interface. For depositions on PAA-treated Si wafers, copper was present primarily
      as Cu0 at the interface and Si was present only as Si0. On PAA-treated Ta
      substrates, XPS analysis indicated Ta was present primarily as Ta0 at the
      metallized interface whereas Ta2O5 dominated the interface of samples prepared
      without the adhesion layers. The technique can be extended to patterned
      substrates using adsorption of acrylic acid or thermal/UV polymerization of
      acrylic acid.

PMID- 15461510
TI  - Geometry-driven wetting transition.
AB  - Wetting states are quantitatively described by the number of inflection points on
      the liquid-vapor interface and by the macroscopic contact angle. The number of
      inflection points required for complete, partial, and pseudopartial wetting is
      determined for geometries with positive, zero, and negative capillary pressures.
      The wetting state of a material system is not always independent of the magnitude
      of the capillary pressure; for example, the wetting state of a fluid inside a
      capillary tube may depend on the capillary radius. In particular, a fluid that
      pseudopartially wets the inside of a tube exhibits a transition to partial
      wetting (or complete wetting) as the capillary radius is decreased.

PMID- 15461511
TI  - Structural characterization of organic multilayers on silicon(111) formed by
      immobilization of molecular films on functionalized Si-C linked monolayers.
AB  - Silicon(111)-H surfaces were derivatized with omega-functionalized alkenes in UV
      mediated and thermal hydrosilylation reactions to give Si-C linked monolayers.
      Additional molecular layers of organic compounds were coupled either directly or
      via linker molecules to the functionalized alkyl monolayers. In the first
      instance, amino-terminated monolayers were prepared from a tert-butoxycarbonyl
      protected omega-aminoalkene followed by removal of the protecting group. Various
      thiols were coupled to the monolayer using a heterobifunctional linker, which
      introduced maleimide groups onto the surface. In the second system, N
      hydroxysuccinimide (NHS) ester-terminated monolayers were formed by reaction of
      Si-H with N-succinimidyl undecenoate. The reactivity of the NHS ester groups was
      confirmed by further modification of the monolayer. The stepwise assembly of
      these multilayer structures was characterized by X-ray reflectometry and X-ray
      photoelectron spectroscopy.

PMID- 15461512
TI  - New approach to writing and simultaneous reading of micropatterns: combining
      surface plasmon resonance imaging with scanning electrochemical microscopy
      (SECM).
AB  - This work establishes the compatibility of surface plasmon resonance imaging (SPR
      i) with the visualization of localized electropolymerization. The "writing" of
      polypyrrole and polypyrrole-oligonucleotide patterns onto thin gold films is
      demonstrated using scanning electrochemical microcopy (SECM), while an optical
      method, SPR-i, simultaneously detected the formed micropatterns. The combination
      of these two methods, SECM/SPR-i, has the advantage of not only controlling the
      patterning process but also providing unique information on the micropattern
      formation. The influence of the pulsing time and the monomer concentration on the
      spot size and its characteristics has been investigated in detail using SPR-i.
      Fluorescence microscopy and atomic force microscopy have also been used to
      support the data obtained by SPR-i.

PMID- 15461513
TI  - Self-assembled monolayers of Ru/Os dinuclear complexes: probing monolayer
      structure and interaction energies by electrochemical means.
AB  - Monolayers of [Ru(bpy)2(micro-1)M2][PF6]4 salts (M = Os, Ru; bpy = 2,2'
      bipyridine, 1 = 4'-(2,2'-bipyridin-4-yl)-2,2':6',2' '-terpyridine, tpy =
      2,2':6',2' '-terpyridine, and 2 = 4'-(4-pyridyl)-2,2':6',2' '-terpyridine) were
      self-assembled on platinum and investigated by fast-scan electrochemistry. The
      electrochemistry of the complexes in solution and confined to the surface in self
      assembled monolayers (SAMs) exhibited an almost ideal behavior. Scan-rate
      dependent measurements of the peak current density (jp) were used to determine
      interaction energies within the monolayer. It is shown that the tpy coordination
      sites of the dinuclear complexes interact more strongly within the SAM than the
      bipyridine-coordinated fragments. This result was supported by peak potential
      shifts, which are due to interaction forces in SAMs. The alignment of the rodlike
      complexes relative to the surface is discussed, and the results of molecular
      mechanics calculations indicate that the species adopt a tilted orientation.

PMID- 15461514
TI  - Molecular orbital theory study on surface complex structures of phosphates to
      iron hydroxides: calculation of vibrational frequencies and adsorption energies.
AB  - Quantum mechanical calculations were applied to resolve controversies about
      phosphate surface complexes on iron hydroxides. Six possible surface complexes
      were modeled: deprotonated, monoprotonated, and diprotonated versions of bridging
      bidentate and monodentate complexes. The calculated frequencies were compared to
      experimental IR frequency data (Persson et al. J. Colloid Interface Sci. 1996,
      177, 263-275; Arai and Sparks J. Colloid Interface Sci. 2001, 241, 317-326.).
      This study suggests that the surface complexes change depending on pH. Four
      possible species are a diprotonated bidentate complex at pH 4-6, either a
      deprotonated bidentate or a monoprotonated monodentate complex at pH 7.5-7.9, and
      a deprotonated monodentate complex at pH 12.8. In addition, reaction energies
      were calculated for adsorption from aqueous solution to determine relative
      stability to form a monoprotonated monodentate complex and a deprotonated
      bidentate complex. According to these results, the monoprotonated monodentate
      complex should be favored. Vibrational frequencies of the monoprotonated
      monodentate and deprotonated bidentate complexes were analyzed with electronic
      effects on the Fe-OP and H-OP bonds.

PMID- 15461515
TI  - Interaction of primary amphipathic cell-penetrating peptides with phospholipid
      supported monolayers.
AB  - The mesoscopic organization adopted by two primary amphipathic peptides, P(beta)
      and P(alpha), in Langmuir-Blodgett (LB) films made of either the pure peptide or
      peptide-phospholipid mixtures was examined by atomic force microscopy. P(beta), a
      potent cell-penetrating peptide (CPP), and P(alpha) mainly differ by their
      conformational states, predominantly a beta-sheet for P(beta) and an alpha-helix
      for P(alpha), as determined by Fourier transform infrared spectroscopy. LB films
      of pure peptide, transferred significantly below their collapse pressure, were
      characterized by the presence of supramolecular structures, globular aggregates
      for P(beta) and filaments for P(alpha), inserted into the monomolecular film. In
      mixed peptide-phospholipid films, similar structures could be observed, as a
      function of the phospholipid headgroup and acyl chain saturation. They often
      coexisted with a liquid-expanded phase composed of miscible peptide-lipid. These
      data strongly suggest that primary amphipathic CPP and antimicrobial peptides may
      share, to some extent, common mechanisms of interaction with membranes.

PMID- 15461516
TI  - Diffraction techniques for nonlamellar phases of phospholipids.
AB  - A neutron diffraction method applicable to nonlamellar phases of substrate
      supported lipid membranes is described and validated. When prepared on a flat
      substrate, the resulting nonlamellar phases have layered symmetry which provides
      some advantages over powder diffraction for detailed structure determination.
      This approach recently led to the detection of a rhombohedral phase and a
      distorted hexagonal phase of lipids. Here the determination of intensity and
      phase information for such phases is demonstrated by application to the hexagonal
      phase of diphytanoyl phosphatidylcholine (DPhPC). The hexagonal symmetry is used
      to verify the data reduction procedure for the intensities of the diffraction
      peaks. Diffraction intensities measured while varying the D2O/H2O ratio in the
      relative humidity was used to solve the phase problem. The neutron scattering
      length density distribution of the hexagonal phase was constructed and analyzed
      to elucidate the packing of the lipid molecules. The structure of DPhPC in the
      hexagonal phase is of interest in connection with its stalk structure in the
      rhombohedral phase. We also found that the incorporation of tetradecane into the
      DPhPC hexagonal phase is limited, similar to the case for dioleoyl
      phosphatidylethanolamine.

PMID- 15461517
TI  - Aminoglycoside antibiotics aggregate to form starch-like fibers on negatively
      charged surfaces and on phage lambda-DNA.
AB  - The water-soluble (> 200 mg/mL) antibiotics tobramycin, kanamycin, and neomycin
      spontaneously produce rigid fibers on negatively charged surfaces (mica,
      graphite, DNA). Atomic force microscopy showed single strands of tobramycin on
      mica at pH 7 with a length of several hundred nanometers and a diameter of 0.5 nm
      and double helices with a diameter of 1.0 nm and a helical pitch of 7 nm. At pH
      13 (NaOH) up to 15 microm long, rigid fibers with a uniform height of 2.4 nm and
      an apparent helical pitch of 30 nm were formed along the sodium silicate channels
      on the surface of mica. Kanamycin and neomycin behaved similarly. Fibers of
      similar length and width, but without secondary structure, were obtained from
      aqueous solutions at pH 7 on amorphous, hydrophilized carbon and characterized by
      transmission electron microscopy. Overstretched phage lambda-DNA strands with a
      height of 1.0 nm on mica did not interact with tobramycin coils at pH 7. After
      treatment with EDTA, however, the height of the magnesium-free lambda-DNA strands
      grew from 1.0 to 3.8 nm after treatment with tobramycin, which suggests a
      wrapping by the supramolecular fibers. Such fibers may interact with F-actin
      fibers in biological cells, which would explain the known aggressiveness of
      aminoglycosides toward bacterial cell membranes and their ototoxicity.

PMID- 15461518
TI  - Silver-colloid-nucleated cytochrome c superstructures encapsulated in silica
      nanoarchitectures.
AB  - We recently discovered that self-organized superstructures of the heme protein
      cytochrome c (cyt. c) are nucleated in buffer by gold nanoparticles. The protein
      molecules within the superstructure survive both silica sol-gel encapsulation and
      drying from supercritical carbon dioxide to form air-filled biocomposite aerogels
      that exhibit gas-phase binding activity for nitric oxide. In this investigation,
      we report that viable proteins are present in biocomposite aerogels when the
      nucleating metal nanoparticle is silver rather than gold. Silver colloids were
      synthesized via reduction of an aqueous solution of Ag+ using either citrate or
      borohydride reductants. As determined by transmission electron microscopy and UV
      visible absorption spectroscopy, the silver nanoparticles vary in size and shape
      depending on the synthetic route, which affects the fraction of cyt. c that
      survives the processing necessary to form a biocomposite aerogel. Silver colloids
      synthesized via the citrate preparation are polydisperse, with sizes ranging from
      1 to 100 nm, and lead to low cyt. c viability in the dried bioaerogels
      (approximately 15%). Protein superstructures nucleated at approximately 10-nm Ag
      colloids prepared via the borohydride route, including citrate stabilization of
      the borohydride-reduced metal, retain significant protein viability within the
      bioaerogels (approximately 45%).

PMID- 15461519
TI  - Effect of cholesterol and phospholipid on the behavior of dialkyl polyoxyethylene
      ether surfactant (2C18E12) monolayers and bilayers.
AB  - Surface pressure-area isotherm, neutron specular reflection, and small-angle
      neutron scattering studies have been carried out to determine the effects of
      added cholesterol and distearoylphosphatidylcholine (DSPC), on the molecular
      structures of monolayers and vesicles containing the dialkyl polyoxyethylene
      ether surfactant, 1,2-di-O-octadecyl-rac-glyceryl-3-(alpha-dodecaethylene glycol)
      (2C18E12). Previous neutron reflectivity studies on 2C18E12 monolayers at the
      air/water interface have shown them to possess a thickness of approximately 24
      angstoms and highly disordered structure with significant intermixing of the
      polymer headgroups and alkyl chains. SANS studies of 2C18E12 vesicles gave a
      bilayer thickness of approximately 51 angstroms. Addition of cholesterol to
      2C18E12 monolayers (1:1 molar ratio), produced a marked condensing effect coupled
      with an increased the layer thickness of approximately 7 angstroms, and in
      vesicles, increased bilayer thickness by approximately 16 angstroms. Monolayers
      consisting of 2C18E12:DSPC:cholesterol (1:1:2 molar ratio), showed a layer
      thickness of approximately 31 angstroms, whereas in vesicles, three-component
      bilayer was found to be only approximately 9 angstroms thicker than those
      possessed by vesicles composed solely of 2C18E12. Mixing between the molecules in
      three-component monolayers was shown to be ideal through analysis of the neutron
      reflectivity data. These findings are discussed in relation to increased ordering
      and decreased headgroup/hydrophobe intermixing within both monolayers and vesicle
      bilayers containing 2C18E12. The inferred increase in molecular order within
      vesicles composed of 2C18E12 with additional cholesterol and phospholipid is used
      as a model for explaining theoretical differences in bilayer permeability.

PMID- 15461520
TI  - Interaction of gramicidin derivatives with phospholipid monolayers.
AB  - A study of the interaction of gramicidin A (gA), tert-butyloxycarbonyl-gramicidin
      (g-BOC), and desformyl gramicidin (g-des) with dioleoyl phosphatidylcholine
      (DOPC) and DOPC/phosphatidylserine (PS) mixed monolayers on a mercury electrode
      is reported in this paper. Experiments were carried out in electrolytes KCl (0.1
      mol dm(-3)) and Mg(NO3)2 (0.05 mol dm(-3)). The channel-forming properties of the
      gramicidins were studied by following the reduction of Tl(I) to Tl(Hg). The
      frequency dependence of the complex impedance of coated electrode surfaces in the
      presence and absence of the gramicidins was estimated between 65,000 and 0.1 Hz
      at potentials of -0.4 V versus Ag/AgCl with 3.5 mol dm(-3) KCl. Epifluorescence
      microscopy was used to qualitatively correlate the interaction of the gramicidin
      peptides with dipalmitoyl phosphatidylcholine (DPPC) and dipalmitoyl
      phosphatidylglycerol (DPPG) at the air-water interface. gA was shown to form Tl+
      conducting channels in a DOPC monolayer, while g-BOC and g-des did not. In DOPC
      30% PS (DOPC-0.3PS) layers, there is a marked increase in channel activity of all
      three gramicidin derivatives. None of the peptides facilitate the permeability of
      the DOPC-0.3PS layer to Cd2+. All three peptides interact with the layer as shown
      by capacitance-potential curves and impedance spectroscopy indicated by
      penetration of the peptide into the dielectric, an increase in surface
      "roughness", and an increased significance of low-frequency relaxations. The
      order of interaction is gA > g-des > g-BOC. The epifluorescence study of DPPC and
      DPPG layers at the air-water interface shows a selective action of the different
      gramicidins.

PMID- 15461521
TI  - Viscoelastic properties of single polysaccharide molecules determined by analysis
      of thermally driven oscillations of an atomic force microscope cantilever.
AB  - We report on single molecule measurements of the viscoelastic properties of the
      polysaccharide dextran using a new approach which involves acquiring the power
      spectral density of the thermal noise of an atomic force microscope cantilever
      while holding the single molecule of interest under force-clamp conditions. The
      attractiveness of this approach when compared with techniques which use forced
      oscillations under constant loading rate conditions is that it is a near
      equilibrium measure of mechanical response which provides a more relevant probe
      of thermally driven biomolecular dynamics. Using a simple harmonic oscillator
      model of the cantilever-molecule system and by subtracting the response of the
      free cantilever taking into account hydrodynamic effects, the effective damping
      zetamol and elastic constant kmol of a single molecule are obtained. The
      molecular elasticity measured by this new technique shows a dependence on applied
      force that reflects the chair-boat conformational transition of the pyranose
      rings of the dextran molecule which is in good agreement with values obtained
      directly from the gradient of a conventional constant loading rate force
      extension curve. The molecular damping is also seen to follow a nontrivial
      dependence on loading which we suggest indicates that it is internal friction and
      not work done on the solvent that is the dominant dissipative process.

PMID- 15461522
TI  - Formation of dispersed nanostructures from poly(ferrocenyldimethylsilane-b
      dimethylsiloxane) nanotubes upon exposure to supercritical carbon dioxide.
AB  - While incompatible block copolymers commonly assemble into several established
      classical or complex morphologies, highly asymmetric
      poly(ferrocenyldimethylsilane-b-dimethylsiloxane) (PFS-b-PDMS) diblock copolymers
      can also self-organize into high-aspect-ratio nanotubes with PDMS corona in the
      presence of PDMS-selective organic solvents. Exposure of these nanotubes on a
      carbon substrate to supercritical carbon dioxide (scCO2), also a PDMS-selective
      solvent, appears to promote partial dissolution of the copolymer molecules. At
      sufficiently high copolymer concentrations, the dissolved molecules subsequently
      re-organize within the scCO2 environment to form new copolymer nanostructures
      that redeposit on the substrate upon scCO2 depressurization. Transmission
      electron microscopy reveals that micelles form under all the conditions examined
      here, whereas nanotubes coalesce and vesicles develop only at relatively high
      temperatures. The extent to which the copolymer nanotubes dissolve and the size
      distribution of the replacement micelles are sensitive to exposure conditions.
      These results suggest that the phase behavior of PFS-b-PDMS diblock copolymers in
      scCO2 may be remarkably rich and easily tunable.

PMID- 15461523
TI  - Probing the dielectric environment surrounding poly(N-isopropylacrylamide) in
      aqueous solution with covalently attached spirobenzopyran.
AB  - The dielectric environment surrounding poly(N-isopropylacrylamide) in aqueous
      solution was investigated by probing with spirobenzopyran covalently attached as
      a side chain to the polymer main chain. Inherent characteristics of the
      spirobenzopyran chromophore were analyzed, and the chromophore was confirmed to
      be suitable to probe the local polar condition around the polymer. Measurements
      for an aqueous polymer solution at various temperatures elucidated that the
      dielectric environment surrounding the polymer changed continuously even in the
      temperature range far below the lower critical solution temperature. This result
      suggested that the local and weak orientation of water molecules around the
      polymer diminished continuously in a preliminary stage of shifting to thermally
      induced phase separation. The dielectric environment surrounding thermoresponsive
      polymer in aqueous solution was investigated by probing with spirobenzopyran
      covalently attached as a side chain to the polymer main chain.

PMID- 15461524
TI  - Interactions of poly(amidoamine) dendrimers with the surfactants SDS, DTAB, and
      C12EO6: an equilibrium and structural study using a SDS selective electrode,
      isothermal titration calorimetry, and small angle neutron scattering.
AB  - Interactions in aqueous solutions of different generations of poly(amidoamine)
      (PAMAM) dendrimers containing amine, hydroxyl, or delta-glucolactone functional
      groups at the periphery with the anionic surfactant sodium dodecyl sulfate (SDS)
      were investigated. We used a SDS-specific electrode (EMF) for SDS monomer
      concentration monitoring, isothermal titration calorimetry (ITC) for binding
      information, and small angle neutron scattering (SANS) for structural studies.
      ITC experiments monitoring the interaction of the dendrimers with cationic
      dodecyltrimethylammonium bromide (DTAB) and nonionic hexaethylene glycol mono-n
      dodecyl ether (C12EO6) showed no significant binding effects. In contrast, SDS
      binds to all of the above dendrimers. EMF and ITC data demonstrated a regular
      trend for both the onset of binding and binding saturation as the generation in
      each family of dendrimers increased. In addition, generation G6 exhibited a
      noncooperative binding process at very low SDS concentrations. Furthermore, the
      onset of cooperative binding in the EMF experiments started at lower
      concentrations as the weight % (w/v), the size, and the numbers of the internal
      or surface groups increased. On the other hand, the binding capacity of the
      dendrimers showed only a small dependence on the above parameters. At SDS
      concentrations approaching the binding limit and also at selective concentrations
      within the binding range, SANS measurements indicated that in all cases the bound
      surfactant is in the micellar form. From the electromotive force (EMF)
      measurements, ITC data, and SANS data, the stoichiometry of the supramolecular
      complexes was determined.

PMID- 15461525
TI  - Synthesis of titania-supported platinum catalyst: the effect of pH on morphology
      control and valence state during photodeposition.
AB  - Solid-supported metal catalysts have been widely used in industrial processes.
      The morphology of coated metal on the support is usually an important factor
      affecting the efficiency of the catalyst. In this study, a photocatalytic process
      is utilized to control the morphology of platinum particles deposited on titania
      (Degussa P-25). More specifically, the effect of pH on the morphology and the
      valence state of platinum nanoparticles was systemically investigated. It is
      found that, via a simple pH-controlled process, various states of platinum (Pt0,
      PtIIO, or PtIVO2) can be deposited onto the support directly at will. In this
      paper, the mechanism of morphology control and the key influencing factors at
      different pH regimes will be discussed. Followed by photodeposition, a H2 thermal
      treatment process was employed to convert the oxides into metal platinum with
      narrow size distribution and even coverage on the supporting titania. Various
      techniques such as transmission electron microscopy, high-resolution transmission
      electron microscopy, energy-dispersive analysis of X-rays, and X-ray
      photoelectron spectroscopy were employed to characterize the prepared titania
      supported platinum particles.

PMID- 15461526
TI  - Nanoscale chemical patterns fabricated by using colloidal lithography and self
      assembled monolayers.
AB  - A method for preparing surfaces with well-defined nanoscale chemical patterns is
      described. The fabrication strategy involves creating nanoscale Au pits
      surrounded by a TiO2 matrix, or vice versa, using colloidal lithography, followed
      by selective functionalization of the Au areas by CH3-terminated alkanethiols.
      Using AFM force spectroscopy with chemically modified tips (OH, CH3), we show
      that the nanopatterned surfaces display strong chemical contrast, in the form of
      hydrophobic CH3 nanopatches surrounded by a hydrophilic TiO2 surface, or vice
      versa. The nanofabrication approach presented here offers several advantages over
      existing patterning technologies, among which are easiness (no sophisticated
      instrumentation is required), versatility (patterns with a range of surface
      functionalities can be prepared), and the possibility to produce patterns over
      large areas at low cost.

PMID- 15461527
TI  - Synthesis and redox behavior of biferrocenyl-functionalized ruthenium(II)
      terpyridine gold clusters.
AB  - Spectroscopic and electrochemical characterizations of ferrocene- and biferrocene
      functionalized terpyridine octanethiolate monolayer-protected clusters were
      investigated and reported. The electrochemical measurements of Ru2+ coordinated
      with 4'-ferrocenyl-2,2':6',2' '-terpyridine and 4'-biferrocenyl-2,2':6',2' '
      terpyridine complexes were dominated by the Ru2+/Ru3+ redox couple (E(1/2) at
      approximately 1.3 V), Fe(2+)/Fe(3+) redox couples (E(1/2) from approximately 0.6
      to approximately 0.9 V), and terpy/terpy-/terpy2- redox couples (E(1/)(2) at ca. 
      1.2 and ca. -1.4 V). The substantial appreciable variations detected in the
      Ru2+/Ru3+ and Fe2+/Fe3+ oxidation potentials indicate that there is an
      interaction between the Ru2+ and Fe2+ metal centers. The coordination of the Ru2+
      metal center with 4'-ferrocenyl-2,2':6',2' '-terpyridine and 4'-biferrocenyl
      2,2':6',2' '-terpyridine leads to an intense 1[(d(pi)Fe)6] -->
      1[d(pi)Fe)5(pi*terpyRu)1] transition in the visible region. The 1[(d(pi)Fe)6] -
      >1[d(pi)Fe)5(pi*terpyRu)1] transition observed at approximately 510 nm revealed
      that there was a qualitative electronic coupling between metal centers. The
      coordination of the Ru2+ transition metal center lowers the energy of the
      pi*terpy orbitals, causing this transition.

PMID- 15461528
TI  - Self-assembly of water-soluble dendrimers into thermoreversible hydrogels and
      macroscopic fibers.
AB  - Hydrogels and macroscopic fibers are formed through the salt-induced self
      assembly of water-soluble polycationic phosphorus dendrimers. Interestingly, the
      hydrogels are thermoreversible and the sol-gel transition temperature can be
      easily tuned in a wide range of temperatures (approximately 2-80 degrees C). The
      effects of different parameters, such as salt nature, dendrimer generation,
      concentration, and temperature, on dendrimer aggregation are examined. The
      macroscopic fibers are prepared by flocculation under flow and observed using
      scanning electron microscopy (SEM) which reveals a microscopic fibrillar
      substructure. We interpret the gelation and flocculation of the polycationic
      dendrimers in terms of colloidal flocculation.

PMID- 15461529
TI  - Crystal structure of a methylamine sorption complex of fully dehydrated fully
      Ca2+ -exchanged zeolite X, |Ca46(CH3NH2)16|[Si100Al92O384]-FAU.
AB  - The structure of a methylamine sorption complex of fully dehydrated fully Ca2+
      exchanged zeolite X, |Ca46(CH3NH2)16|[Si100Al92O384]-FAU, has been determined in
      the cubic space group Fd3 at 21(1) degrees C (a = 24.994(4) angstroms) by single
      crystal X-ray diffraction techniques. The crystal was prepared by ion exchange in
      a flowing stream of 0.05 M aqueous Ca(NO3)2 for 3 days, followed by dehydration
      at 480 degrees C and 2 x 10(-6) Torr for 2 days, and exposure to 160 Torr of
      zeolitically dry methylamine gas at 21(1) degrees C. The structure was determined
      in this atmosphere and was refined, using the 739 reflections for which I > 0, to
      the final error indices R1 = 0.152 and R2 = 0.061. In this structure, Ca2+ ions
      occupy three crystallographic sites. Sixteen Ca2+ ions fill the octahedral site
      at the centers of hexagonal prisms (Ca-O = 2.429(7) angstroms). The remaining 30
      Ca2+ ions are found at two nonequivalent sites II (in the supercages) with
      occupancies of 14 and 16 ions. Each of these Ca2+ ions coordinates to three
      framework oxygens, either at 2.296(7) or 2.334(7) angstroms, respectively.
      Sixteen methylamine molecules have been sorbed per unit cell, two per supercage.
      Each coordinates to one of the latter 16 site-II Ca2+ ions: N-Ca = 2.30(9)
      angstroms. The imprecisely determined N-C bond length, 1.48(23) angstroms,
      differs insignificantly from that in methylamine(g), 1.474(5) angstroms. The
      positions of the hydrogen atoms were calculated. One of the amino hydrogen atoms
      hydrogen bonds to a 6-ring oxygen, and the other forms a bifurcated hydrogen bond
      to two other 6-ring oxygens. The methyl group does not hydrogen bond to anything.

PMID- 15461530
TI  - Cluster size analysis of two-dimensional order in colloidal gold nanoparticle
      arrays.
AB  - A protocol for cluster size distribution analysis was developed in order to
      parametrize local two-dimensional (2D) order in a quantitative manner, using mean
      cluster sizes and fractional hcp cluster formation (fhcp). Cluster size analysis
      was performed on 2D arrays of Au nanoparticles encapsulated in resorcinarene
      tetrathiol, which were organized into close-packed films at aqueous interfaces.
      The degree of monolayer formation and 2D order within the self-assembled
      nanoparticle arrays was observed to be strongly dependent on the amount and type
      of electrolyte (chloride and/or citrate) adsorbed on the nanoparticle surface,
      prior to encapsulation and extraction to the solvent interface. Increasing the
      concentration of adsorbed electrolyte could promote monoparticulate film
      formation but had a variable effect on local 2D order.

PMID- 15461531
TI  - Hydrogen-bonding-directed layer-by-layer assembly of poly(4-vinylpyridine) and
      poly(4-vinylphenol): effect of solvent composition on multilayer buildup.
AB  - This paper describes the buildup of hydrogen-bonding-directed poly(4
      vinylpyridine)/poly(4-vinylphenol) (PVPy/PVPh) multilayer film that was
      fabricated by layer-by-layer (LbL) assembly of PVPy and PVPh from an ethanol
      solution. UV-visible spectroscopy and Fourier transform infrared (FT-IR)
      spectroscopy revealed a uniform deposition process. The interaction between PVPy
      and PVPh was identified as hydrogen bonding through FT-IR spectroscopy and
      temperature-dependent IR spectral changes of the hydrogen-bonded multilayer.
      Notably, we discussed the effect of solvent conditions on the growth of PVPy/PVPh
      multilayer films monitored by UV-visible spectroscopy. It was found that
      increasing the ratio of N,N-dimethylformamide (DMF) in the mixed ethanol/DMF
      solvents resulted in a marked decrease of the amount of polymers adsorbed, which
      was attributed to the increased polarity of the adsorption solutions.
      Furthermore, the solvent stability of PVPy/PVPh multilayer film in mixed
      ethanol/DMF solvents with different DMF ratios was also investigated. As a
      result, a new method for tuning the structure of hydrogen-bonding-directed
      multilayer film was developed.

PMID- 15461532
TI  - On the influence of different surfaces in nano- and submicrometer particle based
      fluorescence immunoassays.
AB  - Recently, numerous attempts have been made to improve the performance of
      fluorescence immunoassays. One way pursued is the substitution of labeling
      molecules by micro- or nanocrystalline dyes. The surfaces of these particulate
      structures are typically engineered by a layerwise assembly of oppositely charged
      polyelectrolytes, the outer layer being constituted of biorecognition molecules,
      for example, immunoglobulins. In this study, we show that amphiphilic polymers
      such as alkylated poly(ethylene imine)s and 1,2-distearoyl-sn-glycero-3
      phosphatoethanolamine-N-[amino(poly(ethylene glycol))] can fully substitute the
      more intricate layer-by-layer technique and evaluate the influence of surface
      charge and particle size on the overall performance of these assays.

PMID- 15461533
TI  - Steric stabilization of core-shell nanoparticles in liquid carbon dioxide at the
      vapor pressure.
AB  - Nondilute nanoparticle dispersions were stabilized in liquid CO2 at 25 degrees C
      at pressures as low as the vapor pressure for greater than 30 min. By modifying
      hydrophilic silica with a trifunctional silylating agent, (heptadecafluoro
      1,1,2,2-tetrahydrodecyl)triethoxy silane, a cross-linked polymer shell was formed
      around the silica core. The presence of the shell led to weaker Hamaker
      interactions between approaching fluoro-silica composite particles and enabled
      dispersibility at weaker solvent conditions (low pressures) than for metals with
      larger Hamaker constants. Steric stabilization of the nanoparticles was provided
      by low-molecular-weight perfluorodecane side chains at the surface of the fluoro
      silica composite shell. Compared to polymeric chains, the perfluorodecane side
      chains are more easily solvated and thus stabilize nanoparticle dispersions in
      CO2 at much lower pressures, even down to the vapor pressure.

PMID- 15461534
TI  - Physicochemical characterization of degradable thermosensitive polymeric
      micelles.
AB  - Amphiphilic AB block copolymers consisting of thermosensitive poly(N-(2
      hydroxypropyl) methacrylamide lactate) and poly(ethylene glycol), pHPMAmDL-b-PEG,
      were synthesized via a macroinitiator route. Dynamic light scattering
      measurements showed that these block copolymers form polymeric micelles in water
      with a size of around 50 nm by heating of an aqueous polymer solution from below
      to above the critical micelle temperature (cmt). The critical micelle
      concentration as well as the cmt decreased with increasing pHPMAmDL block
      lengths, which can be attributed to the greater hydrophobicity of the
      thermosensitive block with increasing molecular weight. Cryogenic transmission
      electron microscopy analysis revealed that the micelles have a spherical shape
      with a narrow size distribution. 1H NMR measurements in D2O showed that the
      intensity of the peaks of the protons from the pHPMAmDL block significantly
      decreased above the cmt, indicating that the thermosensitive blocks indeed form
      the solidlike core of the micelles. Static light scattering measurements
      demonstrated that pHPMAmDL-b-PEG micelles with relatively large pHPMAmDL blocks
      possess a highly packed core that is stabilized by a dense layer of swollen PEG
      chains. FT-IR analysis indicated that dehydration of amide bonds in the pHPMAmDL
      block occurs when the polymer dissolved in water is heated from below to above
      its cmt. The micelles were stable when an aqueous solution of micelles was
      incubated at 37 degrees C and at pH 5.0, where the hydrolysis rate of lactate
      side groups is minimized. On the other hand, at pH 9.0, where hydrolysis of the
      lactic acid side groups occurs, the micelles started to swell after 1.5 h of
      incubation and complete dissolution of micelles was observed after 4 h as a
      result of hydrophilization of the thermosensitive block. Fluorescence
      spectroscopy measurements with pyrene loaded in the hydrophobic core of the
      micelles showed that when these micelles were incubated at pH 8.6 and at 37
      degrees C the microenvironment of pyrene became increasingly hydrated in time
      during this swelling phase. The results demonstrate the potential applicability
      of pHPMAmDL-b-PEG block copolymer micelles for the controlled delivery of
      hydrophobic drugs.

PMID- 15461535
TI  - New insights in the c(4 x 2) reconstruction of hexadecanethiol on Au(111)
      revealed by grazing incidence X-ray diffraction.
AB  - The c(4 x 2) structure of C16H33SH alkanethiol monolayers self-assembled on
      Au(111) has been studied by grazing incidence X-ray diffraction. This structure
      coexists on the surface with the (radical3x radical3)R30 degrees phase. The
      structural refinement of the c(4 x 2) phase has been accomplished by omitting the
      fractional order reflections common to both structures. The surface unit cell
      consists of four symmetry-independent molecules with atomic displacements related
      by couples, such that only two nonequivalent chains are present in the surface
      cell. The stability between neighbor chains is due to van der Waals interactions.
      The substrate plays an important and non-negligible role in the c(4 x 2)
      reconstruction. The lateral and normal substrate relaxations to the surface plane
      are small, and gold atom displacements are lower than 0.25 angstroms but
      contribute very strongly to the fractional order intensities. The molecular
      chains form a close packed structure tilted by 37 degrees from the surface normal
      with no indications of dimer formation between closest S atoms.

PMID- 15461536
TI  - Incorporation and manipulation of coronene in an organic template structure.
AB  - A two-dimensional molecular template structure of 1,3,5-benzenetricarboxylic acid
      (trimesic acid, TMA) was formed on a highly oriented pyrolytic graphite surface
      (HOPG) by self-assembly at the liquid-solid interface. Scanning tunneling
      microscopy (STM) investigations show high-resolution images of the porous
      structure on the surface. After the host structure was created, coronene
      molecules were inserted as guest molecules into the pores. STM results indicate
      that some of the guest molecules rotate inside their molecular bearing. Further
      investigations show that single coronene molecules can be directly kicked out of
      their pores by means of STM.

PMID- 15461537
TI  - Computational study of the self-organization of bidisperse nanoparticles.
AB  - We study computationally the self-organization of bidisperse mixtures of thiol
      stabilized gold particles in two dimensions through random sequential adsorption
      (RSA) coupled with the Metropolis algorithm for determining surface diffusion. It
      was previously shown [Doty et al. Phys. Rev. E 2002, 65, 061503] that ordered
      lattices of bidisperse particles cannot form with hard sphere interactions. Here
      we include the effects of interparticle forces. Osmotic and steric interactions
      provide a repulsive force at close distances, while at longer ranges the van der
      Waals interaction leads to attraction. Two size ratios (sigma) of 0.375 and
      0.577, determined experimentally to form LS (the two-dimensional NaCl analogue)
      and LS2 (the two-dimensional AlB2 analogue) lattices, were studied. The
      calculated jamming limits for RSA fall well below the minimum surface coverage
      necessary for stable ordering as determined by melting simulations. Uniform
      compression of the particles' positions, as a model of the convection and lateral
      capillary forces that would be experienced during solvent evaporation, allowed
      this critical surface coverage to be achieved, and LS lattice formation was
      observed for sigma = 0.375. No LS2 lattice formation was observed for sigma =
      0.577 with compression. The melting coverage of the LS2 lattice far exceeds the
      coverage observed experimentally and so is not observed.

PMID- 15461538
TI  - Electrophoresis of a membrane-coated sphere in a spherical cavity.
AB  - The boundary effect on the electrophoresis of particles covered by a membrane
      layer is discussed by considering a spherical particle in a spherical cavity
      under the conditions where the effect of double-layer polarization can be
      significant. The influence of the key parameters of the system under
      consideration on the electrophoretic mobility of a particle is investigated.
      These include the surface potential; the thickness of the double layer; the
      relative size of the cavity; and the thickness, the fixed charge density, and the
      friction coefficient of the membrane layer. The fixed charge in the membrane
      layer of a particle is found to have a significant influence on its
      electrophoretic behavior. For instance, depending upon the amount of fixed charge
      in the membrane layer, the mobility of a particle may exhibit a local minimum as
      the thickness of the double layer varies.

PMID- 15461540
TI  - Selective serotonin re-uptake inhibitor augmentation in the treatment of negative
      symptoms of schizophrenia.
AB  - Negative symptoms are core features of schizophrenia that respond poorly to first
      generation antipsychotics and present a major obstacle in rehabilitation.
      Patients may be somewhat more responsive to clozapine and second-generation
      antipsychotics but even then, considerable impairment remains. This paper reviews
      the use of selective serotonin re-uptake inhibitor (SSRI) augmentation of
      antipsychotics in the treatment of negative symptoms in schizophrenia. Important
      methodological issues particular to the study of negative symptoms are also
      discussed. Current evidence indicates that at least two SSRIs, fluvoxamine and
      fluoxetine, can ameliorate primary negative symptoms in chronic schizophrenic
      patients treated with first-generation antipsychotics. Onset of improvement may
      be detected within 2 weeks of starting treatment. The combination is well
      tolerated, although as antipsychotic drug concentrations may rise, close
      monitoring of drug doses and possibly drug concentrations is needed. So far,
      evidence regarding SSRI augmentation of second-generation antipsychotics is
      limited and in view of the increasing use of these newer agents, controlled
      studies are urgently needed. SSRI augmentation may be a useful addition to the
      treatment of schizophrenic patients with persistent negative symptoms. The
      paradoxical findings that both clozapine, a serotonin antagonist, and an SSRI
      antidepressant added to antipsychotics, can improve negative symptoms suggests
      that these pharmacologically distinct treatments may share common final
      mechanisms. A better understanding of these mechanisms can shed light on the
      pathogenesis of negative symptoms and provide new targets for drug development.

PMID- 15461541
TI  - Pharmacological augmentation strategies for treatment-resistant obsessive
      compulsive disorder.
AB  - First-line treatment for obsessive-compulsive disorder (OCD) has been well
      established for over a decade, although newer medications, such as citalopram and
      venlafaxine, have emerged to take a place among the older, more established
      serotonin re-uptake inhibitors (SRIs). Unfortunately, as many as 50% of all
      patients with OCD will have symptoms refractory to a single medication treatment
      trial, and a smaller percentage will remain refractory after two or more trials.
      The optimal dosage and duration for first-line trials have been established. Many
      strategies exist for patients who do not respond to first- or second-line
      medication trials, including behavioural therapy, switching to newer SRIs, and
      augmentation with additional medications. This review will focus on medication
      strategies for augmenting SRI treatment response in OCD treatment, including
      neuroleptic and serotonergic agents. Future investigations should include more
      controlled studies and investigate medications that are less likely to trigger
      extrapyramidal symptoms, diabetes mellitus and weight gain.

PMID- 15461542
TI  - Somnambulism (sleepwalking).
AB  - Somnambulism is an arousal parasomnia consisting of a series of complex
      behaviours that result in large movements in bed or walking during sleep. It
      occurs in 2-14% of children and 1.6-2.4% of adults. Occasional benign episodes
      are managed conservatively. However, recurrent sleepwalking with a risk of injury
      to self or others mandates immediate treatment with pharmacotherapy while
      awaiting work-up. The most commonly used medications are benzodiazepines,
      particularly clonazepam, with tricyclic antidepressants and serotonin selective
      re-uptake inhibitors also administered. Treatment of underlying causes such as
      obstructive sleep apnoea, upper airway resistance syndrome, restless legs
      syndrome and periodic limb movements, is currently the best approach and usually
      eliminates somnambulism in children and adults.

PMID- 15461543
TI  - Assessing the efficacy of medical treatments for alcohol use disorders.
AB  - Alcohol use disorders (AUDs) are common health problems that have a significant
      impact on society as a whole. There is a need for more effective treatments. In
      the last two decades, evidence for the efficacy of pharmacological approaches to
      treatment has increased. Although it has long been clear that medications are
      needed for the treatment of the alcohol withdrawal syndrome, the important role
      of medications in the longer-term treatment of AUDs has only recently been
      appreciated. In particular, naltrexone, acamprosate and topiramate appear to be
      efficacious treatments, especially when combined with psychosocial interventions
      that emphasise compliance with medication and encourage treatment retention. The
      goal of this review is to bring together the existing literature supporting the
      usefulness of pharmacological treatments for the alcohol withdrawal syndrome, for
      longer-term treatment of AUDs, and for comorbid AUDs and other psychiatric
      disorders. In addition, opportunities for future research will be identified.

PMID- 15461544
TI  - Pharmacological alternatives for the alleviation of back pain.
AB  - Drugs constitute a convenient option for low back pain and are commonly used.
      However, evidence for their efficacy is meagre. Many drugs used for back pain are
      no more, or only slightly more, effective than placebos. Others have side effects
      that outweigh their usefulness in relieving pain. On the basis of the evidence,
      no drug regimen can be legitimately recommended for back pain. The management of
      back pain requires measures other than drugs. One exception is the use of willow
      (Salix) bark for acute exacerbation of pain. Ironically, for chronic low back
      pain, the most effective and long-lasting outcomes have been documented for
      normal saline by injection into tender points in the lumbar spine.

PMID- 15461545
TI  - Topical 0.05% cyclosporin in the treatment of dry eye.
AB  - Dry eye disease is a common and often underdiagnosed condition that affects > 10%
      of the adult population, > 65 years of age in the US. This condition has been
      classified into two separate, but overlapping, categories--aqueous deficiency and
      evaporative loss. Diagnosis is confused by the lack of a single diagnostic test.
      Fluorescein break-up time is one of the best screening tests and is augmented by
      Lissamine green supravital staining. New concepts of pathogenesis have shown that
      dry eye disease appears to be caused by inflammation mediated by T-cell
      lymphocytes. This finding led to the study and FDA-approval of topical 0.05%
      cyclosporin A (Restasis) for the treatment of dry eye disease. 0.05% Cyclosporin
      A offers the first therapeutic treatment for patients with moderate-to-severe dry
      eye disease due to aqueous deficiency.

PMID- 15461546
TI  - A cost-benefit analysis of chemotherapy for gastric cancer.
AB  - Gastric cancer is the second most common cause of cancer-related deaths
      worldwide. Surgery remains the mainstay of any curative treatment; however, those
      patients who are considered not amenable of curative resection generally receive
      chemotherapy, in order to obtain palliation of symptoms and improved survival.
      Many drugs have been tested in several combination regimens yielding higher
      response rates. In spite of the fact that chemotherapy has been extensively used
      in advanced gastrointestinal cancer, there are few studies that focus on its
      economic costs. The aim of this paper is to review the results of the main
      studies regarding the relationship between the cost of chemotherapy and its
      effectiveness in advanced gastric and gastrointestinal cancer patients.

PMID- 15461548
TI  - Tacrolimus ointment: the treatment of atopic dermatitis and other inflammatory
      cutaneous disease.
AB  - Topical tacrolimus (FK506, Protopic) has been developed and marketed for the
      treatment of atopic dermatitis (AD). Tacrolimus works as an inhibitor of
      calcineurin, which creates a downregulation of the inflammatory cascade. Numerous
      trials have shown the efficacy and safety of tacrolimus in treating AD in both
      adults and children. Additionally, comparison data with other medications
      commonly used for AD, such as topical steroids and pimecrolimus, show improved
      efficacy of tacrolimus. A comprehensive review of the off-label uses of
      tacrolimus in other dermatoses, including psoriasis, lichen planus and
      seborrhoeic dermatitis, is provided. The efficacy of tacrolimus in treating these
      diseases is based on Phase IV clinical trials and on case reports or series in
      the literature. Overall, tacrolimus has proven to be a safe and useful topical
      therapy for many inflammatory dermatological conditions, with AD being the
      principal indication.

PMID- 15461547
TI  - Pharmacoeconomic considerations of multiple sclerosis therapy with the new
      disease-modifying agents.
AB  - Multiple sclerosis (MS) represents the second most common cause of neurological
      disability in young adults. The introduction of treatments that can change the
      natural course of the disease has focused attention on the economic burden of MS.
      There have been fears that the newly approved treatments for MS will ruin
      healthcare systems. Other published economic evaluations stress that the economic
      burden of a disease should be seen in a global perspective and that new
      treatments offer an opportunity to reduce the burden of the disease in the long
      term. This paper reviews a number of key health economic studies in MS, which
      reveal the burden of MS on society and the cost-effectiveness of the new disease
      modifying drugs, and highlight some unresolved issues. All relevant costs,
      including indirect costs and costs of informal care, should be taken into account
      for a global estimation of the cost/benefit balance. Further rigorous economic
      evaluations, focusing on the comparison of different available alternatives, are
      necessary. A major task will be the collection of data on the impact of the new
      disease-modifying therapies in reducing disability progression over the long
      term, outside clinical trials. Gathering this kind of information is of critical
      importance in order to improve the precision of cost-effectiveness estimates in
      the future.

PMID- 15461549
TI  - Etanercept in psoriasis.
AB  - Psoriasis is a chronic skin disorder that affects approximately 2% of the US and
      European populations. Several lines of evidence have demonstrated the correlation
      between elevated levels of TNF and psoriasis, suggesting that interfering with
      the inflammatory effects of TNF may help resolve psoriatic lesions. The
      biological agent, etanercept, is a fully human soluble TNF-receptor fusion
      protein with proven efficacy in the treatment of rheumatoid arthritis, ankylosing
      spondylitis, juvenile rheumatoid arthritis, and psoriatic arthritis. In several
      well-controlled clinical trials, etanercept showed sustained efficacy in reducing
      the signs and symptoms of psoriasis in patients with moderate-to-severe disease.
      With the exception of injection site reactions, adverse event rates were similar
      to placebo and did not increase across higher doses. No opportunistic infections,
      including tuberculosis, were reported. From analysis of the available clinical
      trials, etanercept appears to be an effective and well-tolerated agent for the
      treatment of moderate-to-severe psoriasis.

PMID- 15461550
TI  - Docetaxel as adjuvant and neoadjuvant treatment for patients with breast cancer.
AB  - Developments in the role of adjuvant and neoadjuvant chemotherapy for the
      treatment of patients with breast cancer have focused on the taxes, in
      particular, docetaxel. This paper discusses the rationale for the introduction of
      docetaxel into the management of patients following surgery and also its role in
      those patients with locally-advanced disease, focussing on key clinical trials.
      The addition of docetaxel to standard adjuvant chemotherapeutic regimens does
      seem to result in an increased survival in some patients with early-stage
      disease. In the neoadjuvant setting, the addition of docetaxel to standard
      regimens does increase pathological response rates, which is a surrogate marker
      of eventual outcome.

PMID- 15461551
TI  - A review of oxaliplatin and its clinical use in colorectal cancer.
AB  - Colorectal cancer is one of the leading causes of death from malignant diseases
      in the Western world. Worldwide, approximately 50% of patients who present with
      colorectal cancer will develop metastatic disease and eventually die from this
      malignancy. Recently, significant advances have been made in the medical
      treatment of advanced colorectal cancer with the introduction of novel cytotoxic
      drugs, such as irinotecan and oxaliplatin. Based on the results of recent Phase
      III trials, combination regimens of infusional 5-fluorouracil/leucovorin and
      oxaliplatin (FOLFOX) have emerged as a new standard of care in the palliative and
      adjuvant treatment of colorectal cancer. The addition of biological agents
      targeting angiogenesis or oncogenes such as epidermal growth factor receptor
      (EGFR) to FOLFOX will conceivably further enhance the activity of treatment
      regimens. Making use of all available active therapeutic options in the course of
      disease has significantly improved median overall survival of metastatic
      colorectal cancer into a chronic disease, with implications for treatment
      strategies and pharmacoeconomic considerations.

PMID- 15461552
TI  - Abarelix: the first gonadotrophin-releasing hormone antagonist for the treatment
      of prostate cancer.
AB  - The high incidence of prostate cancer makes it a major healthcare problem and the
      second leading cancer-related cause of death among men in developed countries.
      The hormonal treatment of prostate cancer is indicated for the palliation of
      symptomatic and metastatic disease in older patients, and as neoadjuvant
      treatment of different modalities of radiotherapy. This hormonal treatment is
      based on the study conducted by Huggins in 1940 and consists of androgen
      suppression. Since the clinical availability of the first luteinising hormone
      releasing hormone (LHRH) agonist, no significant improvement has been made in the
      field of medical castration. Taking these data into consideration, the recent
      approval of abarelix by the FDA, the first gonadotrophin-releasing hormone (GnRH)
      antagonist, appears to be promising news. The pharmacology of the molecule and
      the clinical studies that led to FDA approval will be reviewed. The place of GnRH
      antagonists in the treatment modalities of prostate cancer will then be
      discussed.

PMID- 15461553
TI  - Is vasopressin-receptor antagonism an advancement in the treatment of heart
      failure?
AB  - Despite diuretics being used to relieve the fluid retention/congestion associated
      with heart failure (HF), patients with HF are commonly hospitalised due to
      progressive volume retention with an increase in body weight and the
      deterioration of symptoms. Arginine vasopressin acts at vasopressin V2 receptors
      in the kidney as an antidiuretic. Tolvaptan is an orally-active selective V2
      receptor antagonist. In the Acute and Chronic Therapeutic Impact of a Vasopressin
      antagonist in Congestive Heart Failure trial of patients hospitalised with HF,
      tolvaptan 30 mg/day increased urine volume and induced a weight loss of 3.3 kg at
      discharge (placebo; 1.9 kg). In post hoc analyses, mortality was lower with
      tolvaptan in patients with renal impairment and severe congestion, compared to
      placebo. Thus, it seems that tolvaptan is an advancement in the treatment of
      severely decompensated HF.

PMID- 15461554
TI  - Perspectives on cognitive domains, H3 receptor ligands and neurological disease.
AB  - Histamine H(3) receptor agonists and antagonists have been evaluated in numerous
      in vitro and in vivo animal models to better understand how H(3) receptors
      modulate neurotransmitter function in the central nervous system. Likewise,
      behavioural models have explored the hypothesis that changes in neurotransmitter
      release could enhance cognitive function in human diseases. This review examines
      the reported effects of H(3) receptor ligands and how they influence cognitive
      behaviour. These data are interpreted on the basis of different cognitive domains
      that are relevant to neuropsychiatric diseases. Because of the diversity of H(3)
      receptors, their function and their influence on neurotransmitter systems,
      considerable promise exists for H(3) ligands to treat diseases in which aspects
      of learning and memory are impaired. However, because of the complexities of the
      histaminergic system and H(3) receptors and the lack of clinical data so far,
      proof of principle for use in human disease remains to be established.

PMID- 15461555
TI  - The therapeutic potential of Na+ and Ca2+ channel blockers in pain management.
AB  - Chronic pain affects a large percentage of the population, representing a socio
      economic burden. Current treatments are characterised by suboptimal efficacy
      and/or side effects that limit their use. Among several approaches to treating
      chronic pain, voltage-sensitive Ca(2+) and Na(+) channels are promising targets.
      This review evaluates the preclinical evidence that supports the involvement of
      these targets, with specific attention to those subtypes that appear more
      strictly correlated with pain generation and sustainment, as well as those
      compounds that modulate the activity of Ca(2+) and/or Na(+) channels that are
      currently in clinical development for chronic pain conditions.

PMID- 15461556
TI  - Recent advances in the development of multifactorial therapies for the treatment
      of traumatic brain injury.
AB  - Traumatic brain injury (TBI) is one of the leading causes of death and disability
      in the industrialised world and remains a major health problem with serious
      socioeconomic consequences. So far, despite encouraging preclinical results,
      almost all neuroprotection trials have failed to show any significant efficacy in
      the treatment of clinical TBI. This may be due, in part, to the fact that most of
      the therapies investigated have targeted an individual injury factor. It is now
      recognised that TBI is a very heterogeneous type of injury that varies widely in
      its aetiology, clinical presentation, severity and pathophysiology. The
      pathophysiological sequelae of TBI are mediated by an interaction of acute and
      delayed molecular, biochemical and physiological events that are both complex and
      multifaceted. Accordingly, a successful TBI treatment may have to simultaneously
      attenuate many injury factors. Recent efforts in experimental TBI have,
      therefore, focused on the development of neuropharmacotherapies that target
      multiple injury factors and thus improve the likelihood of a successful outcome.
      This review will focus on three such novel compounds that are currently being
      assessed in clinical trials; progesterone, dexanabinol and dexamethasone, and
      provide an update on the progress of both magnesium and cyclosporin A.

PMID- 15461557
TI  - The role of growth factors in the pathogenesis of diabetic retinopathy.
AB  - Diabetic retinopathy (DR) is the most severe of several ocular complications of
      diabetes. The earliest clinical signs of DR are microaneurysms and haemorrhages.
      Later signs include dilated, tortuous irregular veins and retinal non-profusion,
      leading to retinal ischaemia that ultimately results in neovascularisation.
      Diabetic macular oedema, which involves the breakdown of the blood-retinal
      barrier, also occurs and is responsible for a major part of vision loss,
      particularly in Type 2 diabetes. The pathogenesis of DR is very complex. Many
      biochemical mechanisms have been proposed as explanations for the development and
      progression of DR. Chronic hyperglycaemia leads to oxidative injury, microthrombi
      formation, cell adhesion molecule activation, leukostasis and cytokine
      activation. Next, ischaemia-mediated overexpression of growth factors and
      cytokines occurs. These factors include vascular endothelial growth factor,
      insulin-like growth factor-1, angiopoetin-1 and -2, stromal-derived factor-1,
      fibroblast growth factor-2 and tumour necrosis factor. Because of the complex
      interplay between these factors, targeting a single growth factor will be
      unlikely to result in therapeutic inhibition of angiogenesis. These growth
      factors no doubt act in synergy to mediate the steps of angiogenesis, including
      protease production, endothelial cell proliferation, migration and tube
      formation. This review attempts to provide an overview of perspectives regarding
      the pathogenesis of this disease. The focus, however, is on describing the unique
      features of selected relevant factors and how each growth factor may act in a
      synergistic manner with other factors.

PMID- 15461558
TI  - Recent advances in the treatment of polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder that
      presents a challenge for clinical investigators. It is the most common endocrine
      disorder of reproductive-aged women, yet the optimal therapeutic approach is
      unknown because the pathophysiological and molecular basis of the syndrome is not
      fully understood. Currently, the treatment is targeted to the patient's primary
      complaint. Treatment strategies focus on the reduction of clinical manifestations
      of hyperandrogenism (e.g., hirsutism), restoration of regular menses and
      achieving pregnancy. Pharmacological agents available for the treatment of
      hirsutism include androgen suppressors and peripheral androgen blockers. Combined
      oral contraceptive pills are the most commonly used androgen suppressor and the
      treatment of choice for menstrual dysfunction in PCOS patients who do not desire
      pregnancy. The first-line treatment for infertility in PCOS is clomiphene
      citrate, whereas parenteral gonadotropins are commonly used in clomiphene
      resistant patients. The benefits of insulin-sensitising agents for PCOS patients
      have become increasingly clear over the last decade. Metabolic disturbances
      associated with PCOS appear to have important long-term health implications and
      require further attention. This review summarises the current and emerging
      therapeutic strategies for the management of PCOS.

PMID- 15461559
TI  - Beta-lactamase inhibitors: evolving compounds for evolving resistance targets.
AB  - The many and diverse beta-lactamases produced by bacteria, particularly by Gram
      negative pathogens, are increasingly posing a serious threat to the clinical
      utility of beta-lactams. First-generation inhibitors (clavulanic acid, sulbactam,
      tazobactam) focus on Ambler class A enzymes. However, recent structural upgrades
      of class A beta-lactamases (e.g. TEM, SHV) have extended their spectrum (extended
      spectrum beta-lactamases and carbapenemases [Sme, NMC-A, IMI-1]) and have brought
      about the possibility of beta-lactamase-inhibitor resistance. Furthermore, the
      mobilisation and spread of originally chromosomal class C enzymes (CMY, MIR), the
      growing clinical importance of class B enzymes (IMP, VIM), the emergence of
      inhibitor-resistant, broad spectrum class D (OXA) enzymes and the co-existence of
      different classes of beta-lactamases in the same pathogen have spurred research
      toward universal inhibitors. A complicating issue is target accessibility in Gram
      negative bacteria, particularly in Enterobacter, Acinetobacter, Pseudomonas,
      Stenotrophomonas and other organisms, which is necessary in order for the
      inhibitor to synergise with vulnerable beta-lactam antibiotics. Several new,
      broad-spectrum inhibitors have emerged: cephem sulfones and oxapenems are
      upgrades of penam sulfones and oxapenams, respectively, with cephem sulfones
      possibly extending their inhibition to class B metallo-enzymes; and boronates and
      phosphonates are designed de novo, based on common structural and mechanistic
      features of serine beta-lactamases.

PMID- 15461560
TI  - Pharmacological revascularisation in coronary and peripheral vascular disease.
AB  - Therapeutic angiogenesis is a novel approach to the treatment of ischaemic or
      occlusive coronary and peripheral vascular disease. The therapeutic concept is
      based on the restoration of distal blood flow by the enlargement of existing
      vessels and tissue perfusion by the induction of new capillaries. Initial studies
      have focused on the direct application of endothelial growth factors, vascular
      endothelial growth factor and fibroblast growth factor, or the delivery of genes
      using either a plasmid or adenoviral vector. Recently, new angiogenic agents such
      as hypoxia inducible factor-1alpha, fibroblast growth factor-4, Del-1 and
      hepatocyte growth factor have entered clinical testing. Moreover, stem-cell
      therapy or factors mobilising bone marrow progenitor cells have provided evidence
      for a new avenue for therapeutic angiogenesis. Numerous preclinical studies and
      several initial clinical trials have provided encouraging data in support of the
      feasibility of promoting biological revascularisation by the administration of
      angiogenic factors or cells.

PMID- 15461561
TI  - From chemoprevention to chemotherapy: common targets and common goals.
AB  - Three decades of research have revealed that cancer is easier to prevent than to
      treat and that consumption of certain fruits and vegetables can reduce the risk
      of cancer. Whereas chemotherapy is designed to destroy cancer after it appears,
      chemoprevention involves the abrogation or delay in the onset of cancer.
      Regardless of whether a chemopreventive or chemotherapeutic approach is taken,
      cancer is a multifactorial disease that requires modulation of multiple pathways
      and multiple targets. Various molecular targets of chemoprevention are also
      relevant to the therapy of cancer. These targets include the activation of
      apoptosis; suppression of growth factor expression or signalling; downregulation
      of antiapoptotic proteins; suppression of phosphatidylinositol-3'-kinase/Akt, NF
      kappaB, Janus kinase-signal transducer and activator of transcription and
      activator protein-1 signalling pathways; and downregulation of angiogenesis
      through inhibition of vascular endothelial growth factor expression,
      cyclooxygenase-2, matrix metalloproteinase-9, urokinase-type plasminogen
      activator, adhesion molecules and cyclin D1. Pharmacologically safe
      phytochemicals that have been identified from plants or their variant forms can
      modulate these molecular targets. These phytochemicals include genistein,
      resveratrol, dially sulfide, S-ally cysteine, allicin, lycopene, capsaicin,
      curcumin, 6-gingerol, ellagic acid, ursolic acid, betulinic acid, flavopiridol,
      silymarin, anethol, catechins and eugenol. Recent work has shown that these
      phytochemicals also can reverse chemoresistance and radioresistance. Because of
      their pharmacological safety, these agents can be used alone to prevent cancer
      and in combination with chemotherapy to treat cancer.

PMID- 15461562
TI  - The emerging role of solifenacin in the treatment of overactive bladder.
AB  - Although antimuscarinic drug therapy has been proven to be effective in the
      management of patients with symptoms of the overactive bladder syndrome,
      compliance with medication is often affected by the antimuscarinic adverse
      effects of dry mouth, constipation, somnolence and blurred vision. The
      development of bladder-selective M(3)-specific antagonists offers the possibility
      of increasing efficacy whilst minimising adverse effects. At present there are no
      M(3)-specific antagonists currently available although solifenacin and
      darifenacin are both under development and are due to be launched in 2004. The
      purpose of this article is to review the pharmacology and clinical trial data
      available for solifenacin, in addition to examining its role in the treatment of
      the overactive bladder syndrome.

PMID- 15461563
TI  - Ciclesonide: a novel inhaled corticosteroid.
AB  - Inhaled corticosteroids (ICS) are a mainstay in the treatment of persistent
      asthma, a disease with increasing prevalence and cost implications worldwide.
      However, long-term use of currently available ICS is associated with local
      adverse effects that include hoarseness and oral candidiasis. In addition,
      systemic adverse effects including adrenal cortical suppression, osteoporosis,
      growth retardation, cataracts and glaucoma are also present. Ciclesonide is a
      novel ICS, which promises to provide airway anti-inflammatory efficacy that is
      comparable with that of the available ICS in addition to reducing the risk for
      local and systemic adverse events. Ciclesonide is an agent that is inactive until
      it reaches its target site, the lung, where it is converted to its active
      metabolite desisobutyryl-ciclesonide. In addition, other favourable
      pharmacokinetic and pharmacodynamic characteristics such as high protein binding,
      low oral bioavailability and rapid clearance contribute to the efficacy and
      improved systemic safety profile of ciclesonide.

PMID- 15461564
TI  - Suramin: potential in acute liver failure.
AB  - Apoptosis is the first cellular response of the liver to many toxic events,
      including viral hepatitis, alcohol-induced liver disease and
      ischaemia/reperfusion injury. When apoptosis is induced with an antibody to APO
      1, suramin is antiapoptotic in a variety of cell lines (e.g., Jurkat cells,
      HepG2). Jo2 is an antibody to mouse CD95, which kills C57Bl/6 mice, and was used
      as a model of fulminant liver failure in mice. Suramin protected 40% of Jo2
      treated mice from death and delayed death in the other mice. In mice, D
      galactosamine and endotoxin cause apoptotic liver damage, which is mediated by
      TNF. Suramin reduced this liver damage as assessed by serum aminotransferase
      levels, gross liver appearance and apoptosis levels. In contrast, suramin does
      not inhibit necrotic cell death in a rat model of liver transplantation.
      Inhibition of apoptosis with suramin or other more selective agents is an
      approach that should be further investigated in liver failure.

PMID- 15461565
TI  - Raising high-density lipoprotein cholesterol with inhibitors of cholesteryl ester
      transfer protein - a new approach to coronary artery disease.
AB  - Although the low-density lipoprotein (LDL) cholesterol-lowering statins reduce
      the mortality and morbidity associated with coronary artery disease, considerable
      mortality and morbidity remains. Increasing high-density lipoprotein (HDL)
      cholesterol reduces coronary artery disease mortality and morbidity. In healthy
      subjects with mild dyslipidaemia, treatment with JTT-705 decreased cholesteryl
      ester transfer protein (CETP) activity, increased HDL-cholesterol and decreased
      LDL-cholesterol. Similarly, another CETP inhibitor, torcetrapib 120 mg/day has
      recently been shown to increase HDL-cholesterol by 46%, decrease LDL-cholesterol
      by 8% and have no effect on triglycerides in subjects with HDL-cholesterol < 1
      mmol/l. In subjects treated with atorvastatin to lower their LDL-cholesterol
      levels, torcetrapib further lowered LDL-cholesterol while increasing HDL
      cholesterol. In conclusion, raising HDL-cholesterol with inhibitors of CETP is a
      new approach to coronary artery disease that requires further investigation,
      especially in patients with coronary artery disease.

PMID- 15461566
TI  - SMi 4th Annual Conference on Neurodegenerative Disorders: a focus on Alzheimer's
      and Parkinson's disease.
AB  - This was a small (approximately 50 people) focused meeting on neurodegenerative
      disorders, with most of the speakers being from biotechnology or major
      pharmaceutical companies. The meeting covered a range of topics including
      introductions to Alzheimer's disease and Parkinson's disease, examples of
      targeting particular receptors/pathways, animal models and preclinical studies,
      clinical trial design and the use of biomarkers and imaging modalities. The major
      focus in the Alzheimer's disease area was finding symptomatic treatments that are
      superior to acetylcholinesterase inhibitors and the extensive efforts that are
      ongoing to develop disease-modifying therapies. In terms of Parkinson's disease
      there are now several reports examining the effects of dopamine agonists versus
      3,4-dihydroxyphenylalanine on disease progression, and ongoing work with growth
      factors (e.g., glial cell line-derived neurotrophic factor) and mixed lineage/c
      Jun N-terminal kinase inhibitors, such as CEP-1347. Small molecules that enhance
      endogenous signalling and repair pathways were also discussed.

PMID- 15461567
TI  - Transgenic plant-derived pharmaceuticals - the practical approach?
AB  - Production of biopharmaceuticals in transgenic plants would involve the creation
      of a new industry. Those transgenic plants, including staple food crops, could
      provide many benefits to people all over the world. However, the new industry
      might require a strict regulation system. It is probable that such a strict
      system would not be acceptable to Japan or to most developing countries. Many
      countries should use non-food crops for production of biopharmaceuticals and take
      on more simple systems. The new industry must develop strategies for promoting
      the benefits of transgenic plant-derived biopharmaceuticals on both the domestic
      and worldwide scales.

PMID- 15461568
TI  - Immunopathogenesis and immunotherapeutic approaches to type 1A diabetes.
AB  - It is now clear that type 1A (immune-mediated) diabetes develops in genetically
      susceptible individuals where, prior to the onset of overt hyperglycaemia, there
      is usually a long prodrome characterised by the presence of autoimmunity directed
      at islet beta cells. It is the destruction of these insulin-producing cells that
      results in loss of metabolic regulation and the resultant hyperglycaemia and
      severe sequelae of type 1A diabetes. An extensive body of animal data and a
      developing body of human studies are now addressing therapies directed at this
      root immune cause of type 1A diabetes. Therapies can be considered in terms of
      the disease stage at which they are applied and in terms of their effects on the
      immune system (e.g., generalised immunosuppression, immunomodulation, antigen
      specific therapies and tolerance-inducing therapies). As T cells are the primary
      mediators of islet beta cell destruction, it is likely that improved therapies
      and monitoring of T cell autoimmunity will be necessary to develop a safe and
      effective therapy for type 1A diabetes.

PMID- 15461569
TI  - B7-H1-targeted immunotherapy for head and neck cancer.
AB  - Manipulation of defined costimulatory pathways may provide a means to direct the
      immune response against head and neck cancer. Three broad hurdles serve as
      relative obstacles to effective clinical translation of reagents designed to
      alter costimulatory function. First is an expanding, but still limited,
      understanding of the biological function of each individual costimulatory
      pathway. Second is the paucity of reagents suitable for clinical application.
      Third is the limited number of valid model systems to evaluate the utility of
      these novel reagents prior to clinical intervention. This review focuses on the
      role of a recently discovered costimulatory molecule, B7-H1, as a model for the
      development of novel strategies for immunotherapy of head and neck cancer.

PMID- 15461570
TI  - Orally delivered malaria vaccines: not too hard to swallow.
AB  - Vaccines offer efficient and cost-effective protection against a wide range of
      infectious diseases. Unfortunately, no effective vaccine is yet available against
      malaria, and this infection remains one of the most important causes of human
      morbidity and mortality in the developing world. Over the past two decades a
      number of candidate proteins for inclusion in a subunit vaccine have been
      identified. Malariologists believe that an effective malaria vaccine will need to
      include multiple proteins that induce protective immune responses against
      different stages of the Plasmodium life cycle. The construction of such
      multivalent vaccines is beset by considerable logistical difficulties, not least
      of which is how to deliver them to a population living in endemic areas. Compared
      with other routes of vaccine administration, oral delivery has several advantages
      that make it an attractive strategy for vaccine development. This review
      summarises the progress towards an oral vaccine delivery system for malaria and
      discusses the feasibility of this approach.

PMID- 15461571
TI  - Human cancer gene therapy with cytokine gene-modified cells.
AB  - Cytokines can impede tumour growth and activate innate and adaptive immune
      responses, leading to elimination of cancer cells. For many years, it was
      believed that systemic administration of recombinant cytokines might become a
      standard treatment of different cancer types. However, due to a high toxicity of
      therapeutic doses and a low efficacy, even in combination with chemotherapy, this
      strategy is generally not accepted. On the other hand, cancer gene therapy
      approaches utilising cells modified with cytokine genes seem to represent a novel
      promising approach. For the last decade, numerous Phase I and II clinical trials
      evaluating different therapies based on cytokine gene-modified cells have been
      carried out. In the early studies, several strategies have been shown to improve
      clinical outcomes and induce strong antitumour immune responses. Recently, a few
      prospective, randomised, Phase III clinical trials have been initiated in order
      to finally determine the efficacy of particular cancer immunogene therapy
      strategies. This article reviews the present status and perspectives of clinical
      trials of cancer immunotherapies utilising cytokine gene-modified cells.

PMID- 15461572
TI  - Cytokine gene therapy for malignant glioma.
AB  - Despite advances in surgical and adjuvant therapy, the prognosis for malignant
      gliomas remains dismal. Malignant gliomas, like other malignancies, are able to
      overcome host immune defences through a variety of mechanisms that have become
      increasingly well-characterised over the past decade. However, this
      'immunologically privileged' status of the brain is not absolute. Systemic
      immunisation with brain-specific antigens can induce immune responses that are
      manifested in the CNS, such as experimental allergic encephalomyelitis. The
      efficacy of peripheral immunisation against brain tumours has also been
      demonstrated in preclinical models. Based on these observations, clinical trials
      of peripheral immunisations with brain tumour-derived antigens have been
      initiated. A limitation of this approach is that the immunological environment
      within brain tumours is suboptimal for functions of antitumour immune effector
      cells. As a means to overcome this issue, delivery of cytokine genes to the
      tumour site may reverse the inhibitory immunological environment of the brain
      tumours and enhance the efficacy of peripheral vaccine-induced immune effector
      cells. The brain tumour environment may also be rendered more immunologically
      favourable by the delivery of additional antigen-presenting cells that can
      provide infiltrating effector cells with secondary activation signals. Indeed,
      the authors' recent data indicate that the injection of intracranial tumours with
      dendritic cells secreting interferon-alpha enhances the efficacy of peripheral
      vaccinations with tumour-specific antigens by cross-priming tumour antigen
      specific T cells in the cervical lymph nodes. This review highlights the recent
      literature on cytokine gene therapy for brain tumours, and proposes the effective
      use of cytokine gene delivery both at the site of vaccines (i.e., the site of
      antigen presentation) and within the target brain tumours (i.e., the site where
      the effector cells exert their antitumour immunity). Successful immunogene
      therapy for brain tumours requires detailed understanding of cytokine functions
      and the use of them at the appropriate stages/sites of the immunological milieu.

PMID- 15461573
TI  - Applications of gene therapy for familial amyloidotic polyneuropathy.
AB  - Familial amyloidotic polyneuropathy (FAP), caused by mutated transthyretin (TTR),
      is the common form of hereditary generalised amyloidosis. As TTR is predominantly
      synthesised in the liver, liver transplantation is now considered an effective
      treatment for FAP to halt the production of variant TTR. However, this invasive
      therapy has several problems, leading to a requirement for a non-invasive
      treatment to be developed. At present, gene therapy for FAP has focused on two
      therapeutic strategies for suppressing variant TTR gene expression. The first is
      inhibition of variant TTR mRNA expression by antisense or ribozymes, and the
      other is the repair of mutated TTR gene by chimaeraplasts or single-stranded
      oligonucleotides. In particular, targeted gene repair is considered to be a
      promising tool for gene therapy because the effect can last permanently and the
      method is more suitable for proteins with a short plasma half-life. This article
      summarises the general concept of gene therapy and reviews the recent data on
      gene therapy for FAP.

PMID- 15461574
TI  - Medicinal application of long synthetic peptide technology.
AB  - This review covers the latest developments of long synthetic peptide technology
      for the rapid identification and development of malaria vaccine candidates and
      immunological modulators. A brief description of the two most common solid-phase
      synthetic procedures, together with the latest advances in optimisation of
      peptide chain assembly and analytical instrumentation, is given, with special
      attention to non-specialists. Several examples of vaccine candidates developed in
      the authors' or their collaborators' laboratories are also provided.

PMID- 15461575
TI  - Regulatable aptamers in medicine: focus on antithrombotic strategies.
AB  - Proteins generally execute the key physiological activities required for normal
      growth and homeostasis. As such, many different classes of proteins, including
      proteases, kinases, cellular receptors and signalling proteins, represent
      attractive targets for diagnosis or therapy. Aptamers are small nucleic acid
      molecules that function as direct protein inhibitors, much like monoclonal
      antibodies. After a decade of intensive research, technology development and
      initial clinical evaluation, aptamers have now demonstrated broad potential as
      direct protein ligands and inhibitors, and thus represent an exciting class of
      compounds for the development of new therapeutic and diagnostic agents. This
      review will discuss the basic properties and isolation of aptamers, their use in
      animals and the clinic, and describe an exciting recent advance in the
      development of antidotes to certain aptamers, which will add a repertoire of new
      agents with regulatable activity for clinical use.

PMID- 15461576
TI  - Inhibition of hepatitis viral replication by siRNA.
AB  - Small interfering RNA (siRNA)-mediated sequence-specific gene silencing is a
      powerful tool to inhibit endogenous and exogenous gene expression, and it holds
      great potential to prevent and eradicate viral infection, for which existing
      therapy is inadequate, such as HIV, hepatitis B virus (HBV) and hepatitis C virus
      (HCV). A number of studies have documented the effectiveness of siRNA against HBV
      or HCV at various regions of the viral genome in infected human hepatoma cell
      lines. Selected siRNA may reduce the production of viral replicons, as well as
      structural or non-structural proteins by > 90%. Only a few in vivo studies that
      demonstrated the efficacy of siRNA in the suppression of HBV replication in mice
      are available. Thus, reliable models of HBV and HCV infection in small animals or
      non-human primates are needed to evaluate the delivery and efficacy of siRNA as a
      therapeutic modality for viral hepatitis.

PMID- 15461577
TI  - DNA vaccines against anthrax.
AB  - DNA vaccination is vaccination at its simplest. Due to renewed interest in
      vaccination against anthrax and other biothreat agents, a genetic immunisation
      approach offers attractive possibilities for rapid, responsive vaccine
      development. DNA vaccination against anthrax is an active area of research
      showing promising results at present, which in the short-term and in the future
      could form the basis for new advances in multi-agent vaccine development. The
      anthrax 'model' constitutes an important experimental system for genetic
      immunisation technology development.

PMID- 15461578
TI  - Pertussis vaccination for adolescents and adults.
AB  - Following the introduction of vaccines, the incidence of pertussis declined;
      however, since 1990, a progressive increase was noted, even in highly immunised
      populations. Periodic pertussis outbreaks are due to suboptimal efficacy of the
      vaccine and waning immunity with increasing age. A significant proportion of
      adolescents and adults with a prolonged cough present Bordetella pertussis, and
      infection is often transmitted to infants too young to be vaccinated. A high
      vaccination coverage in the whole population would be necessary to interrupt the
      circulation of B. pertussis, but immunisation programmes for adolescents and
      adults have been introduced recently and are accepted with difficulty. The lack
      of cost-benefit analysis and consistent epidemiological data makes it difficult
      to assess the role of pertussis elimination among public health priorities. At
      present, programmes targeted at risk groups for close contacts with infants are
      the most convenient for adult population, as more epidemiological and economic
      evidence is needed before a universal strategy can be discussed.

PMID- 15461579
TI  - Immunological monitoring of cancer vaccine therapy.
AB  - Immunological treatment of malignant diseases in humans aiming at the induction
      and proliferation of antigen-specific T cells has made rapid progress in recent
      years. A growing number of tumour-associated antigens, potentially synergistic
      combinations with adjuvants, and various routes of application provide new
      opportunities for cancer vaccination. Therefore, a highly accurate assessment of
      vaccine-induced T cell responses is required. Three T cell assays (tetramers,
      intracellular cytokine flow cytometry and ELISPOT assay) have emerged as first
      line methods for monitoring T cell induction during vaccination. These assays are
      relatively easy to perform, reliable, sensitive and allow an ex vivo T cell
      analysis at the single cell level. Although at this stage assays are not a
      defined surrogate marker for clinical efficacy, they already provide information
      concerning the immunological potency of a given vaccine. In particular, comparing
      immune responses under various treatment conditions will help to develop more
      clinically efficient tumour vaccination. Novel assays, such as CD107 staining,
      human leukocyte antigen/green fluorescent protein-antigen-presenting cells or
      microarrays, and assays determining functions, such as proliferation assays, are
      beginning to complement first-line monitoring assays.

PMID- 15461580
TI  - Oncolytic measles viruses for cancer therapy.
AB  - New strategies using biological agents are being developed to treat cancer. Live
      viruses are among these new agents. Virotherapy uses replication-competent viral
      vectors with strong oncolytic properties. With the use of molecular virology
      techniques, viruses have been genetically engineered to replicate selectively in
      tumour cells and are under preclinical and clinical investigation at present.
      Measles virus (MV) is being used for this purpose. Replication-competent
      attenuated Edmonston B measles vaccine strain (MV-Edm) is non-pathogenic and has
      potent antitumour activity against several human tumours. The virus is
      selectively oncolytic in tumour cells, eliciting extensive cell-to-cell fusion
      and ultimately leading to cell death. Therefore, MV-Edm is a safe and efficient
      means to kill tumour cells. Further improvements in existing MV vectors may
      increase tumour selectivity and oncolytic activity. This review discusses the
      discovery and development of replication-competent oncolytic MV for cancer
      therapy.

PMID- 15461581
TI  - Breaking dogmata to help patients: non-myeloablative haematopoietic stem cell
      transplantation.
AB  - Various dogmata have been broken as a consequence of the evolution of knowledge
      in the area of allogeneic haematopoietic stem cell (HSC) transplantation. The
      following is now clear: for the successful engraftment of allogeneic HSC, bone
      marrow ablation of the recipient is not required; HSCs create their own space
      through graft-versus-host reactions; several malignancies can be eradicated by
      the graft-versus-tumour effect; HSC allografting can be conducted on an out
      patient basis; HSC allografting can be done in aged or debilitated individuals;
      HSC allografting can be achieved without transfusion of blood products; and the
      costs of the allografting procedures can be substantially diminished. Despite the
      fact that HSC allografting with reduced intensity conditioning may be related to
      several disadvantages, such as mixed chimaerism and relapse of the malignancy,
      breaking these dogmata has resulted in availability of HSC allografting to a
      larger number of individuals worldwide, thus offering true curative therapeutic
      options to patients who otherwise would not qualify to be given these
      opportunities.

PMID- 15461582
TI  - Cloning, expression and characterization of a sialidase gene from Arthrobacter
      ureafaciens.
AB  - Sialidases have recently been used in the processing of clinically relevant
      asialoproteins. The Arthrobacter ureafaciens sialidase (EC 3.2.1.18) exhibits
      broad substrate specificity and is often used in such applications. We have
      employed an expression cloning strategy to isolate the A. ureafaciens sialidase.
      The clone encodes a 990-amino-acid 104 kDa open-reading-frame protein containing
      three domains: an N-terminal catalytic domain, a linker domain with an
      immunoglobulin-like fold and a C-terminal domain of unknown function. Expression
      in Escherichia coli indicates that the sialidase promoter was active in E. coli.
      Overexpression in E. coli resulted in several truncated forms. A 54 kDa truncated
      variant was generated, expressed and purified, and its feasibility for use in an
      erythropoietin desialylation process was demonstrated.

PMID- 15461583
TI  - Stimulation of hepatocytic AMP-activated protein kinase by okadaic acid and other
      autophagy-suppressive toxins.
AB  - Autophagic activity in isolated rat hepatocytes is strongly suppressed by OA
      (okadaic acid) and other PP (protein phosphatase)-inhibitory toxins as well as by
      AICAR (5-aminoimidazole-4-carboxamide riboside), a direct activator of AMPK (AMP
      activated protein kinase). To investigate whether AMPK is a mediator of the
      effects of the toxin, a phosphospecific antibody directed against the activation
      of phosphorylation of the AMPK alpha (catalytic)-subunit at Thr172 was used to
      assess the activation status of this enzyme. AICAR as well as all the toxins
      tested (OA, microcystin-LR, calyculin A, cantharidin and tautomycin) induced
      strong, dose-dependent AMPKalpha phosphorylation, correlating with AMPK activity
      in situ (in intact hepatocytes) as measured by the AMPK-dependent phosphorylation
      of acetyl-CoA carboxylase at Ser79. All treatments induced the appearance of
      multiple, phosphatase-sensitive, low-mobility forms of the AMPK alpha-subunit,
      consistent with phosphorylation at several sites other than Thr172. The flavonoid
      naringin, an effective antagonist of OA-induced autophagy suppression, inhibited
      the AMPK phosphorylation and mobility shifting induced by AICAR, OA or
      microcystin, but not the changes induced by calyculin A or cantharidin. AMPK may
      thus be activated both by a naringin-sensitive and a naringin-resistant
      mechanism, probably involving the PPs PP2A and PP1 respectively. Neither the
      Thr172-phosphorylating protein kinase LKB1 nor the Thr172-dephosphorylating PP,
      PP2C, were mobility-shifted after treatment with toxins or AICAR, whereas a
      slight mobility shifting of the regulatory AMPK beta-subunit was indicated.
      Immunoblotting with a phosphospecific antibody against pSer108 at the beta
      subunit revealed a naringin-sensitive phosphorylation induced by OA, microcystin
      and AICAR and a naringin-resistant phosphorylation induced by calyculin A and
      cantharidin, suggesting that beta-subunit phosphorylation could play a role in
      AMPK activation. Naringin antagonized the autophagy-suppressive effects of AICAR
      and OA, but not the autophagy suppression caused by cantharidin, consistent with
      AMPK-mediated inhibition of autophagy by toxins as well as by AICAR.

PMID- 15461585
TI  - Measurement of critical lower limb tissue hypoxia by coupling chemical and
      optical techniques.
AB  - It has been a long-term goal to develop non-invasive methods that can detect
      critical levels of tissue hypoxia to help in the management of chronic lower limb
      ischaemia. In the present study, skeletal muscle oxygenation was measured using a
      new Clark-type TCPO2 [transcutaneous PO2 (partial pressure of O2)]/PCO2 (partial
      pressure of CO2) monitoring system and optical NIRS (near-infrared spectroscopy)
      at graded levels of hypoxaemia using a rabbit model (n=6). The TCPO2/PCO2 probe
      was placed on the shaved hindlimb to record SPO2 (skin PO2) and SPCO2 (skin PCO2)
      continuously. A pair of NIRS probes were placed on the limb to monitor HbO2
      (oxyhaemoglobin) and Hb (deoxyhaemoglobin). Graded hypoxaemia was achieved by
      stepwise reductions of FiO2 (fraction of inspired O2) from 30% to 6%. Animals
      were allowed to recover after each episode of hypoxia at an FiO2 of 30% as
      indicated by normalized arterial blood PO2. There was a significant (P<0.05)
      decrease in SPO2 with all grades of hypoxaemia and no significant changes in
      SPCO2. There was a significant (P<0.05) increase in muscle Hb with all grades of
      hypoxaemia and a significant (P<0.05) decrease in HbO2 when FiO2 was below 15%. A
      significant correlation was found between the SPO2 and HbO2 (r=0.92, P<0.001) and
      both were significantly correlated with arterial blood PO2 (P<0.001). The new
      TCPO2/PCO2 system, in addition to its application for the assessment of
      conditions such as chronic venous insufficiency where alteration in skin
      oxygenation occurs solely, also has potential in conditions such as peripheral
      vascular disease where both skin and muscle oxygenation may be affected.

PMID- 15461584
TI  - Direct oxidation of polymeric substrates by multifunctional manganese peroxidase
      isoenzyme from Pleurotus ostreatus without redox mediators.
AB  - VPs (versatile peroxidases) sharing the functions of LiP (lignin peroxidase) and
      MnP (manganese peroxidase) have been described in basidiomycetous fungi Pleurotus
      and Bjerkandera. Despite the importance of this enzyme in polymer degradation,
      its reactivity with polymeric substrates remains poorly understood. In the
      present study, we first report that, unlike LiP, VP from Pleurotus ostreatus
      directly oxidized two polymeric substrates, bovine pancreatic RNase and Poly R
      478, through a long-range electron pathway without redox mediators. P. ostreatus
      produces several MnP isoenzymes, including the multifunctional enzyme MnP2 (VP)
      and a typical MnP isoenzyme MnP3. MnP2 (VP) depolymerized a polymeric azo dye,
      Poly R-478, to complete its catalytic cycle. Reduction of the oxidized
      intermediates of MnP2 (VP) to its resting state was also observed for RNase.
      RNase inhibited the oxidation of VA (veratryl alcohol) in a competitive manner.
      Blocking of the exposed tryptophan by N-bromosuccinimide inhibited the oxidation
      of RNase and VA by MnP2 (VP), but its Mn2+-oxidizing activity was retained,
      suggesting that Trp-170 exposed on an enzyme surface is a substrate-binding site
      both for VA and the polymeric substrates. The direct oxidation of RNase and Poly
      R by MnP2 (VP) is in sharp contrast with redox mediator-dependent oxidation of
      these polymers by LiP from Phanerochaete chrysosporium. Molecular modelling of
      MnP2 (VP) revealed that the differences in the dependence on redox mediators in
      polymer oxidation by MnP2 (VP) and LiP were explained by the anionic
      microenvironment surrounding the exposed tryptophan.

PMID- 15461586
TI  - Human xylosyltransferase I: functional and biochemical characterization of
      cysteine residues required for enzymic activity.
AB  - XT-I (xylosyltransferase I) is the initial enzyme in the post-translational
      biosynthesis of glycosaminoglycan chains in proteoglycans. To gain insight into
      the structure-function relationship of the enzyme, a soluble active form of human
      XT-I was expressed in High Five insect cells with an apparent molecular mass of
      90 kDa. Analysis of the electrophoretic mobility of the protein under non
      reducing and reducing conditions indicated that soluble XT-I does not form
      homodimers through disulphide bridges. In addition, the role of the cysteine
      residues was investigated by site-directed mutagenesis combined with chemical
      modifications of XT-I by N-phenylmaleimide. Replacement of Cys471 or Cys574 with
      alanine led to a complete loss of catalytic activity, indicating the necessity of
      these residues for maintaining an active conformation of soluble recombinant XT-I
      by forming disulphide bonds. On the other hand, N-phenylmaleimide treatment
      showed no effect on wild-type XT-I but strongly inactivated the cysteine mutants
      in a dose-dependant manner, indicating that seven intramolecular disulphide
      bridges are formed in wild-type XT-I. The inhibitory effect of UDP on the XT-I
      activity of C561A (Cys561-->Ala) mutant enzyme was significantly reduced compared
      with all other tested cysteine mutants. In addition, we tested for binding to UDP
      agarose beads. The inactive mutants revealed no significantly different
      nucleotide-binding properties. Our study demonstrates that recombinant XT-I is
      organized as a monomer with no free thiol groups and strongly suggests that the
      catalytic activity does not depend on the presence of free thiol groups,
      furthermore, we identified five cysteine residues which are critical for enzyme
      activity.

PMID- 15461587
TI  - Depletion of iNOS-derived nitric oxide by prostaglandin H synthase-2 in
      inflammation-activated J774.2 macrophages through lipohydroperoxidase turnover.
AB  - PGHS-2 (prostaglandin H synthase-2) is induced in mammalian cells by pro
      inflammatory cytokines in tandem with iNOS [high-output ('inducible') nitric
      oxide synthase], and is co-localized with iNOS and nitrotyrosine in human
      atheroma macrophages. Herein, murine J774.2 macrophages incubated with
      lipopolysaccharide and interferon gamma showed induction of PGHS-2 and generated
      NO using iNOS that could be completely depleted by 12(S)-HPETE [12(S)
      hydroperoxyeicosatetraenoic acid; 2.4 muM] or hydrogen peroxide (500 microM)
      (0.42+/-0.084 and 0.38+/-0.02 nmol x min(-1) x 10(6) cells(-1) for HPETE and H2O2
      respectively). COS-7 cells transiently transfected with human PGHS-2 also showed
      HPETE- or H2O2-dependent NO decay (0.44+/-0.016 and 0.20+/-0.04 nmol x min(-1) x
      10(6) cells(-1) for 2.4 microM HPETE and 500 microM H2O2 respectively). Finally,
      purified PGHS-2 consumed NO in the presence of HPETE or H2O2 (168 and 140 microM
      x min(-1) x microM enzyme(-1) for HPETE and H2O2 respectively), in a haem
      dependent manner, with 20 nM enzyme consuming up to 4 microM NO. K(m) (app)
      values for NO and 15(S)-HPETE were 1.7+/-0.2 and 0.45+/-0.16 microM respectively.
      These data indicate that PGHS-2 catalytically consumes NO during peroxidase
      turnover and that pro-inflammatory cytokines simultaneously upregulate NO
      synthesis and degradation pathways in murine macrophages. Catalytic NO
      consumption by PGHS-2 represents a novel interaction between NO and PGHS-2 that
      may impact on the biological effects of NO in vascular signalling and
      inflammation.

PMID- 15461588
TI  - Identification of filamin C as a new physiological substrate of PKBalpha using
      KESTREL.
AB  - We detected a protein in rabbit skeletal muscle extracts that was phosphorylated
      rapidly by PKBa (protein kinase Ba), but not by SGK1 (serum- and glucocorticoid
      induced kinase 1), and identified it as the cytoskeletal protein FLNc (filamin
      C). PKBa phosphorylated FLNc at Ser2213 in vitro, which lies in an insert not
      present in the FLNa and FLNb isoforms. Ser2213 became phosphorylated when C2C12
      myoblasts were stimulated with insulin or epidermal growth factor, and
      phosphorylation was prevented by low concentrations of wortmannin, at which it is
      a relatively specific inhibitor of phosphoinositide 3-kinase. PD 184352 [an
      inhibitor of the classical MAPK (mitogen-activated protein kinase) cascade]
      and/or rapamycin [an inhibitor of mTOR (mammalian target of rapamycin)] had no
      effect. Insulin also induced the phosphorylation of FLNc at Ser2213 in cardiac
      muscle in vivo, but not in cardiac muscle that does not express PDK1 (3
      phosphoinositide-dependent kinase 1), the upstream activator of PKB. These
      results identify the muscle-specific isoform FLNc as a new physiological
      substrate for PKB.

PMID- 15461589
TI  - Exploitation of KESTREL to identify NDRG family members as physiological
      substrates for SGK1 and GSK3.
AB  - We detected a protein in rabbit skeletal muscle extracts that was phosphorylated
      rapidly by SGK1 (serum- and glucocorticoid-induced kinase 1), but not by protein
      kinase Ba, and identified it as NDRG2 (N-myc downstream-regulated gene 2). SGK1
      phosphorylated NDRG2 at Thr330, Ser332 and Thr348 in vitro. All three residues
      were phosphorylated in skeletal muscle from wild-type mice, but not from mice
      that do not express SGK1. SGK1 also phosphorylated the related NDRG1 isoform at
      Thr328, Ser330 and Thr346 (equivalent to Thr330, Ser332 and Thr348 of NDRG2), as
      well as Thr356 and Thr366. Residues Thr346, Thr356 and Thr366 are located within
      identical decapeptide sequences GTRSRSHTSE, repeated three times in NDRG1. These
      threonines were phosphorylated in NDRG1 in the liver, lung, spleen and skeletal
      muscle of wild-type mice, but not in SGK1-/- mice. Knock-down of SGK1 in HeLa
      cells using small interfering RNA also suppressed phosphorylation of the
      threonine residues in the repeat region of NDRG1. The phosphorylation of NDRG1 by
      SGK1 transformed it into an excellent substrate for GSK3 (glycogen synthase
      kinase 3), which could then phosphorylate Ser342, Ser352 and Ser362 in the repeat
      region. Incubation of HeLa cells with the specific GSK3 inhibitor CT 99021
      increased the electrophoretic mobility of NDRG1 in HeLa cells, demonstrating that
      this protein is phosphorylated by GSK3 in cells. Our results identify NDRG1 and
      NDRG2 as physiological substrates for SGK1, and demonstrate that phosphorylation
      of NDRG1 by SGK1 primes it for phosphorylation by GSK3.

PMID- 15461592
TI  - Abstracts submitted for the 69th Annual Scientific Meeting of the American
      College of Gastroenterology. October 29-November 3, 2004, Orlando, Florida, USA.

PMID- 15461591
TI  - The antagonistic regulation of human MUC4 and ErbB-2 genes by the Ets protein
      PEA3 in pancreatic cancer cells: implications for the
      proliferation/differentiation balance in the cells.
AB  - The human transmembrane mucin MUC4 is aberrantly expressed in 75% of pancreatic
      ductal adenocarcinomas, whereas no expression is found in normal pancreas.
      Therefore MUC4 appears as a useful biological marker for the diagnosis of ductal
      adenocarcinomas. Since rat Muc4 was shown to interact with ErbB-2 tyrosine kinase
      receptor and to either promote cell survival and differentiation or cell
      proliferation, it is postulated that MUC4 may also participate in pancreatic
      carcinogenesis. Our aim was to investigate in parallel the role of the Ets factor
      PEA3 in MUC4 and ErbB-2 transcriptional regulation in pancreatic cancer cells.
      Two MUC4-expressing WD (well-differentiated) (CAPAN-1 and -2) and one MUC4-non
      expressing poorly differentiated (PANC-1) cell lines were used. The three cell
      lines express ErbB-2 at different levels. By co-transfection and site-directed
      mutagenesis, we show that PEA3 is a transactivator of the MUC4 promoter and that
      the -216 and -2368 PEA3 binding sites of the MUC4 promoter are essential. We also
      demonstrate that PEA3 acts in synergy with c-Jun and specificity protein 1 to
      transactivate the proximal region of the MUC4 promoter and increase MUC4 mRNA
      levels in WD cells. These results suggest that MUC4 is a new target gene of the
      Ets factor PEA3 in pancreatic cancer cells. In contrast, PEA3 represses the
      transcriptional activity of two fragments of the ErbB-2 promoter in a dose
      dependent manner and decreases the endogenous ErbB-2 mRNA levels in WD cell
      lines. Thus, PEA3, by its capacity to up-regulate the epithelial marker MUC4 and
      to down-regulate the ErbB-2 oncogene, appears as a key regulator of the
      differentiation/proliferation balance in pancreatic cancer cells.

PMID- 15461590
TI  - Lipid phosphate phosphatase-1 regulates lysophosphatidic acid-induced calcium
      release, NF-kappaB activation and interleukin-8 secretion in human bronchial
      epithelial cells.
AB  - LPA (lysophosphatidic acid), a potent bioactive phospholipid, elicits diverse
      cellular responses through activation of the G-protein-coupled receptors LPA1
      LPA4. LPA-mediated signalling is partially regulated by LPPs (lipid phosphate
      phosphatases; LPP-1, -2 and -3) that belong to the phosphatase superfamily. This
      study addresses the role of LPPs in regulating LPA-mediated cell signalling and
      IL-8 (interleukin-8) secretion in HBEpCs (human bronchial epithelial cells).
      Reverse transcription-PCR and Western blotting revealed the presence and
      expression of LPP-1-3 in HBEpCs. Exogenous [3H]oleoyl LPA was hydrolysed to [3H]
      mono-oleoylglycerol. Infection of HBEpCs with an adenoviral construct of human
      LPP-1 for 48 h enhanced the dephosphorylation of exogenous LPA by 2-3-fold
      compared with vector controls. Furthermore, overexpression of LPP-1 partially
      attenuated LPA-induced increases in the intracellular Ca2+ concentration,
      phosphorylation of IkappaB (inhibitory kappaB) and translocation of NF-kappaB
      (nuclear factor-kappaB) to the nucleus, and almost completely prevented IL-8
      secretion. Infection of cells with an adenoviral construct of the mouse LPP-1
      (R217K) mutant partially attenuated LPA-induced IL-8 secretion without altering
      LPA-induced changes in intracellular Ca2+ concentration, phosphorylation of
      IkappaB, NF-kappaB activation or IL-8 gene expression. Our results identify LPP-1
      as a key regulator of LPA signalling and IL-8 secretion in HBEpCs. Thus LPPs
      could represent potential targets in regulating leucocyte infiltration and airway
      inflammation.

PMID- 15461593
TI  - Neurogenic mechanisms in bronchial inflammatory diseases.
AB  - Neurogenic inflammation encompasses the release of neuropeptides from airway
      nerves leading to inflammatory effects. This neurogenic inflammatory response of
      the airways can be initiated by exogenous irritants such as cigarette smoke or
      gases and is characterized by a bi-directional linkage between airway nerves and
      airway inflammation. The event of neurogenic inflammation may participate in the
      development and progression of chronic inflammatory airway diseases such as
      allergic asthma or chronic obstructive pulmonary disease (COPD). The molecular
      mechanisms underlying neurogenic inflammation are orchestrated by a large number
      of neuropeptides including tachykinins such as substance P and neurokinin A, or
      calcitonin gene-related peptide. Also, other biologically active peptides such as
      neuropeptide tyrosine, vasoactive intestinal polypeptide or endogenous opioids
      may modulate the inflammatory response and recently, novel tachykinins such as
      virokinin and hemokinins were identified. Whereas the different aspects of
      neurogenic inflammation have been studied in detail in laboratory animal models,
      only little is known about the role of airway neurogenic inflammation in human
      diseases. However, different functional properties of airway nerves may be used
      as targets for future therapeutic strategies and recent clinical data indicates
      that novel dual receptor antagonists may be relevant new drugs for bronchial
      asthma or COPD.

PMID- 15461594
TI  - Diagnosis of nonimmediate reactions to beta-lactam antibiotics.
AB  - Nonimmediate manifestations (i.e. occurring more than 1 h after drug
      administration), particularly maculopapular and urticarial eruptions, are common
      during beta-lactam treatment. The mechanisms involved in most nonimmediate
      reactions seem to be heterogeneous and are not yet completely understood.
      However, clinical and immunohistological studies, as well as analysis of drug
      specific T-cell clones obtained from the circulating blood and the skin, suggest
      that a type-IV (cell-mediated) pathogenic mechanism may be involved in some
      nonimmediate reactions such as maculopapular or bullous rashes and acute
      generalized exanthematous pustulosis. In the diagnostic work-up, the patient's
      history is fundamental; patch testing is useful, together with delayed-reading
      intradermal testing. The latter appears to be somewhat more sensitive than patch
      testing, but also less specific. In case of negative allergologic tests,
      consideration should be given to provocation tests, and the careful
      administration of the suspect agents. With regard to in vitro tests, the
      lymphocyte transformation test may contribute to the identification of the
      responsible drug. Under the aegis of the European Academy of Allergology and
      Clinical Immunology (EAACI) interest group on drug hypersensitivity and the
      European Network for Drug Allergy (ENDA), in this review we describe the general
      guidelines for evaluating subjects with nonimmediate reactions to beta-lactams.

PMID- 15461595
TI  - Blomia tropicalis, a mite whose time has come.

PMID- 15461596
TI  - Practice evidence to put evidence into practice.

PMID- 15461597
TI  - A clinical survey on compliance in the treatment of rhinitis using nasal
      steroids.
AB  - BACKGROUND: In the treatment of persistent rhinitis, the observed efficacy with
      intranasal steroids in clinical practice often falls short of that reported in
      clinical trials. We postulate that this could be due to patient non-compliance
      and thus designed this study to evaluate the impact of patient compliance on the
      efficacy of treatment in patients with persistent rhinitis. METHODS: Sixty-three
      consecutive adult patients with allergic and non-allergic rhinitis, treated with
      intranasal triamcinolone acetonate, were included in the study. Compliance was
      determined both by direct questioning and by measuring the weight of medication
      consumed (WMC) after 30 days of therapy. Nasal symptom scores were used to
      determine treatment efficacy. RESULTS: Forty-nine patients (77.8%) reported a
      forgetfulness of using medication for a few times (1-5 times) during the
      treatment period. Less than 50% compliance was reported by one patient (1.6%) but
      detected in seven patients (11%) by WMC. There was a significant (P < 0.001)
      improvement in mean total symptom score before (7.45 +/- 1.99) and after (3.59 +/
      2.72) treatment in patients with WMC of at least 50%, but not when WMC was <50%
      (8.43 +/- 1.72 vs 6.29 +/- 2.43; P = 0.114). With >50% WMC, the positive
      predictive values for relief of each symptom were rhinorrhoea: 78%, nasal itch:
      70%, nasal obstruction: 67% and sneezing: 65%. CONCLUSION: Patients compliance
      has a significant impact on treatment efficacy with intranasal steroids. There is
      a discrepancy between reported and actual compliance. It is thus important to
      establish the actual compliance when evaluating patients who fail to respond to
      therapy.

PMID- 15461598
TI  - Cross-reactivity to eel, eelpout and ocean pout in codfish-allergic patients.
AB  - Fish allergy is one of the most common food allergies in both children and adults
      and patients with allergic reactions to one fish species have in many cases been
      given the advice to avoid all fish, without further evaluation. The possible
      common reactivity between different fish species is not well studied. Because of
      this and a possible exploitation of fish species hitherto not much used in the
      Scandinavian diet ocean pout, eelpout and eel were evaluated. We examined the
      serological and biological cross-reactivity of these species in double-blind
      challenged-confirmed codfish-allergic patients using CAP, Maxisorp-radio
      allergosorbent test (RAST) inhibition, western blot, skin prick test (SPT) and
      histamine release (HR). All 18 codfish allergic patients had specific IgE to
      ocean pout, eelpout and eel determined by Maxisorp-RAST. All four fish species
      could induce basophil HR using blood from 16 of 18 patients and all patients
      tested reacted in SPT. This study demonstrates that patients with a verified
      clinical allergy to codfish in a high frequency express biological cross
      reactivity to other fish species. By RAST inhibition this common reactivity was
      shown to be a true cross-reactivity.

PMID- 15461599
TI  - Allergenicity and cross-reactivity of Russian olive pollen (Eleagnus
      angustifolia).
AB  - BACKGROUND: The purposes of this study were: to determine the prevalence of
      sensitization and immunochemical characterization of Eleagnus angustifolia pollen
      (Russian olive) that belongs to the family Eleagnaceae. METHODS: A total of 134
      patients with rhinoconjunctivitis and/or asthma were studied. Its allergenicity,
      cross-reactivity with olive pollen and the presence of Ole e 1 and Ole e 4-like
      molecules were evaluated. RESULTS: Eleagnus angustifolia pollen was detected from
      May to June. Seventy-three of 134 (30.5%) had positive skin test to E.
      angustifolia, all of them were positive to olive. There was a good correlation
      between specific immunoglobulin (Ig)E levels to E. angustifolia and Olea europaea
      (r = 0.77, P = 0.002). Sodium dodecyl sulphate polyacrylamide gel electrophoresis
      (SDS-PAGE) immunoblots revealed major IgE-binding bands in the E. angustifolia
      extract of 43 and 63.7 kDa. The E. angustifolia extract was not able to inhibit
      olive, whereas O. europaea inhibited E. angustifolia up to 41%. The presence of
      Ole e 1- and Ole e 4-like allergens in E. angustifolia extract was confirmed by
      enzyme-linked immunosorbent (ELISA) inhibition assays. Nasal challenge with E.
      angustifolia was positive in three of six patients with positive skin test to
      both pollens and negative in five patients with positive skin test only to O.
      europaea. CONCLUSIONS: This study confirms that E. angustifolia is capable of
      sensitizing individuals in Madrid. A minimal-to-moderate cross-reactivity with
      olive pollen was established, suggesting some cross-reactivity but not excluding
      co-sensitization.

PMID- 15461600
TI  - Allergy to jackfruit: a novel example of Bet v 1-related food allergy.
AB  - BACKGROUND: Jackfruit allergy has been reported just once. It is unknown whether
      this food allergy is caused by direct sensitization or cross-sensitization to
      pollen allergens. OBJECTIVE: Establish whether jackfruit allergy is linked to
      birchpollen allergy. METHODS: Two jackfruit allergic patients and five patients
      with birchpollen-related apple allergy were recruited. Sensitization to pollen
      and plant foods was assessed by skin prick test (SPT), radio-allergosorbent test
      (RAST) and immunoblot. RAST analysis was performed for Bet v 1 and Mal d 1. Cross
      reactivity was evaluated by RAST and immunoblot-inhibition. Biological activity
      of immunoglobulin E (IgE) was measured by basophil histamine release. Allergy to
      jackfruit was evaluated by double-blind placebo-controlled food challenge
      (DBPCFC) or open challenge (OC). RESULTS: In both patients DBPCFC confirmed the
      reported jackfruit allergy. SPT was 41 and 27 mm2 and specific IgE to jackfruit
      was 5.9 and 0.8 IU/ml, respectively. Immunoblot analysis revealed IgE reactivity
      at Mr of approximately 17 kDa. The Bet v 1-related nature of this allergen in
      jackfruit was demonstrated by RAST and immunoblot inhibition. To assess whether
      jackfruit allergy might be common in patients with combined birchpollen-fruit
      allergy, five such patients underwent an OC with jackfruit. All five had OA-like
      symptoms. CONCLUSIONS: Jackfruit allergy can be added to the list of birchpollen
      related food allergies. Increased consumption of this fruit will result in a rise
      in allergic reactions.

PMID- 15461601
TI  - Assessment of the relation between short and intermediate term growth in children
      with asthma treated with inhaled glucocorticoids.
AB  - OBJECTIVE: To assess the relation between short-term growth and intermediate term
      growth in children with asthma treated with inhaled glucocorticoids. DESIGN: An
      open 12 months parallel group trial with visits to the clinic on day 1, after 2,
      4, 8, 12, 20, 28, 36, 44 and 52 weeks. SETTING: Outpatient clinic in a secondary
      referral centre. SUBJECTS: Sixteen children with asthma aged 9 (6-13) years; 16
      matched healthy subjects. METHODS: Knemometry and stadiometry. INTERVENTIONS: Dry
      powder inhaled budesonide 200 microg twice daily. PRIMARY OUTCOME MEASURES: Intra
      group comparisons of mean lower leg growth rates. SECONDARY OUTCOME MEASURES:
      Inter-group comparisons of mean lower leg growth rates and intra-group
      comparisons of mean height-standard deviation scores. RESULTS: One year mean
      lower leg growth rate (0.36 mm/week) did not differ from the rates during the 2
      (0.27 mm/week; P = 0.23), 4 (0.33 mm/week; P = 0.54), 8 (0.36 mm/week; P = 0.79)
      or 12 (0.33 mm/week; P = 0.49) weeks intervals in the asthma group. Similarly, in
      the healthy children 2 (0.56 mm/week; P = 0.63), 4 (0.46 mm/week; P = 0.36), 8
      (0.43 mm/week; P = 0.49) and 12 (0.43 mm/week; P = 0.66) weeks mean growth rates
      did not vary statistically significantly from the 1 year growth rate (0.42
      mm/week). Mean lower leg growth rates, however, were consistently lower during
      all periods in the children with asthma (P = 0.02-0.03). At completion of the
      study mean height-standard deviation score in the asthma group (-0.19) was
      significantly suppressed as compared with the score at study entry (-0.03) (P =
      0.02), whereas no statistically significant variation was detected in the control
      group. CONCLUSIONS: Short-term lower leg growth rates are consistent with
      intermediate term growth rates in group studies in children with asthma treated
      with inhaled dry powder budesonide 400 microg/day. Short-term group knemometry
      should be an integral part of growth evaluations of new inhaled glucocorticoids,
      doses and inhalation devices in children with asthma.

PMID- 15461602
TI  - Evaluation of the Asthma Life Quality test for the screening and severity
      assessment of asthma.
AB  - BACKGROUND: Asthma Life Quality (ALQ) test, a 20-question questionnaire developed
      by the American College of Allergy, Asthma and Immunology, has been shown to be
      useful for asthma diagnosis. We aimed to determine the relation between ALQ
      scores and (a) diagnosis of asthma; (b) physician's classification of asthma
      severity according to National Institutes of Health/Global Initiative for Asthma
      (GINA). METHODS: Standard translation and cultural adaptation to Portuguese was
      performed. Patients self-administered the ALQ in the waiting room; the attending
      allergist classified them, blindly for the test. The scores of nonasthmatics were
      compared with those of asthma patients. Asthma patients were analyzed in two
      severity groups: intermittent and mild persistent asthma (IMPA), and moderate and
      severe persistent asthma (MSPA); sensitivity, specificity, positive and negative
      predictive values were calculated and receiver operating characteristic curve
      plotted. Logistic regression analysis models were computed. RESULTS: From 283
      patients, 237 tests were analyzed. Non-asthmatic patients ALQ scores (mean +/-
      SD) were 6 +/- 4 and, for asthmatics, 10 +/- 5 [mean difference 4.6 (95%CI 3.3
      5.9)]. The odds of positive diagnosis increased 1.27 times (95%CI 1.17-1.38) for
      each one-unit increase in the test. For asthma severity ALQ scores were 9 +/- 4
      for IMPA, 15 +/- 3 for MSPA [difference 6.0 (95%CI 4.8-7.1)]; with a sensitivity
      of 88% and specificity of 74% for a score of 12. The odds of MSPA increased 1.49
      times (95%CI 1.28-1.74) per unit increase in ALQ. CONCLUSIONS: ALQ can help both
      to identify patients with asthma and to differentiate those more likely to have
      moderate/severe asthma. These are relevant characteristics for the possible use
      of this simple, self-administered questionnaire in the assessment of asthma
      patients needing additional medical management.

PMID- 15461603
TI  - Randomized controlled open study of sublingual immunotherapy for respiratory
      allergy in real-life: clinical efficacy and more.
AB  - BACKGROUND: Some aspects of sublingual immunotherapy (SLIT) still need to be
      addressed: magnitude of the clinical efficacy, effect on the bronchial
      hyperreactivity adherence to treatment, preventive effect. We attempted to
      clarify these points in a randomized open, controlled, two parallel group study
      in a real-life setting. METHODS: Five hundred and eleven patients with allergic
      rhinitis with or without intermittent asthma were randomized to drugs only or
      drugs + SLIT (rate 2 : 3) for 3 years. The clinical score (symptoms + drug
      intake) was measured each year during the allergen exposure. Pulmonary function
      test, methacholine challenge and skin tests were performed at the beginning and
      at the end of the study. Adherence to treatment was assessed by measuring the
      consumed extract. RESULTS: Three hundred and nineteen patients received SLIT and
      192 drugs only. Dropouts were 15% in the SLIT group and 12% in the controls.
      There was a significant improvement of clinical scores in the SLIT group:
      baseline 147 +/- 3.3, first year 72.9 +/- 1.3, second year 68.3 +/- 1.8, third
      year 54.7 +/- 2.8 (P < 0.0001 vs baseline). CONTROL GROUP: baseline 138 +/- 2.3,
      first year 124.1 +/- 3.7, second year 111 +/- 3.3, third year 121 +/- 3.8 (P =
      NS). Only four patients reported systemic itching. Adherence was >80% in 72% and
      >60% in 18% of patients. The number of patients with a positive MCh challenge
      decreased significantly after 3 years only in the SLIT group. New skin
      sensitizations appeared in 38% of the controls and in 5.9% of the SLIT patients
      (P = 0.01). CONCLUSION: Sublingual immunotherapy approximately halved the
      clinical scores and significantly reduced the bronchial hyperreactivity.
      Similarly to subcutaneous immunotherapy, SLIT displayed a preventive effect on
      the onset of new skin sensitizations. The adherence rate was quantitatively
      satisfactory.

PMID- 15461604
TI  - Preferential expression of IgG2b in nose draining cervical lymph nodes and its
      putative role in mucosal tolerance induction.
AB  - Induction of intranasal tolerance prevents the body from eliciting unwanted
      immune responses against harmless antigens that enter the body through the nasal
      mucosa. To study the intrinsic capacities of the cervical, nose draining lymph
      nodes (CLN), which are essential for tolerance induction, genes that are
      differentially expressed in CLN and not in peripheral lymph nodes (PLN) were
      characterized. The gene that is predominantly overexpressed in CLN codes for
      IgG2b. This is confirmed by a higher percentage of IgG2b+ B220+ cells in CLN
      compared with any PLN. However, this predominance of IgG2b-positive B cells in
      the CLN is not specific for the lymph node itself but rather determined by the
      region drained by lymph nodes at the cervical site, as transplanted PLN at these
      locations show a comparable predominance. It was demonstrated that IgG2b, when
      compared with IgG1, led to differential activation of dendritic cells (DC)
      through Fc receptor signalling. The results point to a unique local combination
      of cells and factors in the nose draining CLN leading to highly specialized
      immune reactivity. The results point out that predominance of a distinct IgG
      isotype in a lymphoid environment may lead to highly specialized immune
      reactivity.

PMID- 15461605
TI  - Is secondary lymphoid-organ chemokine (SLC/CCL21) much more than a constitutive
      chemokine?
AB  - Chemokines are a superfamily of small cytokines with activities ranging from
      leukocyte traffick to hematopoiesis, angiogenesis, and tissue organogenesis.
      Secondary lymphoid-organ chemokine (SLC/CCL21) was originally reported as a
      chemokine constitutively expressed by stromal cells and high endothelial venules
      in secondary lymphoid tissues and endothelium of afferent lymphatics, directing
      CCR7+ cells. More recently, others and we have demonstrated that SLC/CCL21 is up
      regulated in different skin inflammatory conditions. Thereafter, this molecule is
      much more than a constitutive chemokine, which could play a role in effector and
      regulatory immune functions.

PMID- 15461606
TI  - Effect of immunotherapy on asthma progression, BHR and sputum eosinophils in
      allergic rhinitis.
AB  - BACKGROUND: Bronchial hyperresponsiveness (BHR) and airway inflammation are
      frequently associated with allergic rhinitis, and may be important risk factors
      for the development of asthma. Specific immunotherapy (SIT) reduces symptom in
      subjects with allergic rhinitis, but the mechanisms are not clear. AIMS OF THE
      STUDY: To assess the effect of Parietaria-SIT on asthma progression, rhinitic
      symptoms, BHR, and eosinophilic inflammation. METHODS: Nonasthmatic subjects with
      seasonal rhinitis were randomly assigned to receive Parietaria pollen vaccine (n
      = 15) or matched placebo (n = 15). Data on symptoms and medication score, BHR to
      methacholine, eosinophilia in sputum were collected throughout the 3-year study.
      RESULTS: By the end of the study, in the placebo group, symptoms and medication
      scores significantly increased by a median (interquartile range) of 121% (15-280)
      and 263% (0-4400) respectively (P < 0.01), whereas no significant difference was
      observed in the SIT group. We found no significant changes in sputum eosinophils
      and BHR to methacholine in both groups throughout the study. Nine of 29
      participants developed asthma symptoms during the study; of these, only two
      subjects (14%) in the SIT-treated group (P = 0.056). CONCLUSIONS: Parietaria-SIT
      reduces symptom and rescue medication scores, but no changes in BHR to
      methacholine or sputum eosinophilia were observed. Moreover, Parietaria-SIT
      appears to prevent the natural progression of allergic rhinitis to asthma,
      suggesting that SIT should be considered earlier in the management of subjects
      with allergic rhinitis.

PMID- 15461607
TI  - IgE binding to pepsin-digested water soluble and insoluble wheat proteins.
AB  - BACKGROUND: Positive skin prick tests to wheat are a common finding among atopic
      patients, but only a minor fraction of these patients show immediate clinical
      symptoms after wheat ingestion. The aim of this study was to evaluate the
      allergenicity of wheat proteins after pepsin treatments. METHODS: Six patients
      with positive specific IgE and/or skin prick test to soluble wheat proteins and
      to gluten were studied. Five of them had no symptoms after wheat ingestion and
      showed a negative oral challenge test. All sera were analysed with extracts
      obtained after pepsin hydrolysis during different time periods of water-soluble
      and insoluble wheat proteins by IgE immunoblotting. RESULTS: A pepsin-sensitive
      allergen of around 35 kDa was recognized by the five atopic negative wheat oral
      challenge patients in the undigested water-insoluble extract. A patient showing
      immediate urticaria after wheat ingestion detected a pepsin-resistant allergen
      with similar molecular weight. Finally, an inhalation-induced asthma patient
      recognized water-soluble proteins (of around 14 kDa) that could correspond to the
      alpha-amylase inhibitors. CONCLUSIONS: Our immunoblotting method shows better
      correlation with the clinical symptoms than skin prick test and CAP results.
      Pepsin resistance of the acetic acid-soluble wheat proteins may be responsible
      for the immediate symptoms of the patient who presented immediate urticaria.

PMID- 15461608
TI  - Safety of rush hymenoptera venom immunotherapy.

PMID- 15461609
TI  - Pharaoh Menes' death after an anaphylactic reaction--the end of a myth.

PMID- 15461610
TI  - The frequency of mouse and rat allergy among allergic individuals in Izmir (a
      preliminary report).

PMID- 15461611
TI  - Skin prick test with hen's egg: whole egg or egg white?

PMID- 15461612
TI  - Severe respiratory allergy induced by indirect exposure to rabbit dander: a case
      report.

PMID- 15461613
TI  - Anaphylaxis to raw carrot not linked to pollen allergy.

PMID- 15461614
TI  - Allergic suture material contact dermatitis induced by ethylene oxide.

PMID- 15461616
TI  - Meningeal extramedullar haematopoiesis.

PMID- 15461617
TI  - Mycobacterium fortuitum infection in a patient with chronic lymphocytic
      leukaemia.

PMID- 15461618
TI  - New insights into the pathophysiology and management of osteoporosis in patients
      with beta thalassaemia.
AB  - Osteoporosis represents an important cause of morbidity in adult patients with
      thalassaemia major (TM). The pathogenesis of osteoporosis in TM is
      multifactorial, and includes bone marrow expansion, endocrine dysfunction and
      iron overload. Additional genetic factors, such as the COLIA 1 gene polymorphism,
      seem to play an important role in the development of low bone mass in these
      patients. However, the mechanisms through which these factors lead to bone loss
      have not been completely clarified. The diminished osteoblast function is
      accompanied by a comparable or even greater increase in osteoclast activity. The
      receptor activator of nuclear factor-kappa B (RANK)/RANK ligand
      (RANKL)/osteoprotegerin (OPG) pathway has been recently recognized as the final,
      dominant mediator of osteoclast proliferation and activation. There is increased
      evidence that this pathway interferes in the pathogenesis of thalassaemia-induced
      osteoporosis. Currently, bisphosphonates that are potent inhibitors of osteoclast
      function have been used in TM patients with encouraging results. This review
      attempts to summarize all the novel data for the biology of bone damage in TM. It
      also describes the results of all major studies that have investigated the
      effects of different treatment modalities for TM-induced osteoporosis, their mode
      of action, and the future implications of their use.

PMID- 15461619
TI  - Bone marrow histopathology in peripheral T-cell lymphomas.
AB  - Peripheral T-cell lymphomas (PTCL) account for 10-15% of all lymphoproliferative
      disorders in the western hemisphere. In PTCL, bone marrow biopsy is performed to
      establish the diagnosis, rule out other pathology, assess the extent of disease
      and monitor treatment response. The frequency and histology of bone marrow
      involvement varies greatly between different clinicopathological entities
      recognized by the World Health Organisation (WHO) classification, reflecting the
      differences in the underlying biology. Some lymphomas, such as angioimmunoblastic
      T-cell lymphoma, show nodular and/or interstitial pattern of infiltration with
      accompanying reactive changes. Others, including hepatosplenic T-cell lymphoma
      and large granular lymphocyte leukaemia, are characterized by intrasinusoidal
      infiltration. In many instances the pathological features are subtle and
      immunohistochemical and molecular studies are required for the diagnosis.
      Histological appearances may overlap with a variety of reactive T-cell
      proliferations and other malignancies. Furthermore PTCL frequently induce
      secondary changes in the marrow that may obscure the neoplastic infiltrate. The
      diagnosis often requires critical integration of the information obtained from
      clinical features, peripheral blood, bone marrow aspirate and biopsy findings. In
      this article we review the histopathology of bone marrow biopsy in PTCL within
      the context of the new WHO classification.

PMID- 15461620
TI  - Low intensity warfarin: is it clinically useful in venous thromboembolism
      management?
AB  - Therapy for a first episode of venous thromboembolism (VTE) typically includes a
      vitamin K antagonist, such as warfarin, for 3-6 months at an international
      normalized ratio (INR) of 2-3. After the cessation of warfarin therapy,
      unprovoked VTE is associated with a recurrence rate of 5-15% per year. Prolonging
      initial therapy does not reduce the recurrence risk once warfarin is discontinued
      and is not routinely recommended for such patients. The Prevention of Recurrent
      Venous Thromboembolism (PREVENT) and Extended Low-Intensity Anticoagulation for
      Thromboembolism (ELATE) trials were undertaken to evaluate the efficacy and
      safety of low-intensity warfarin (INR 5-2) in this population. While both trials
      demonstrated that low-intensity warfarin offers substantial protection against
      recurrent VTE, only the ELATE trial included a standard intensity arm; this arm
      showed a significantly lower recurrence rate and a major bleed rate that,
      surprisingly, was similar to the low-intensity arm. There still remains no
      consensus that long-term warfarin at an INR of 2-3 should be recommended for all
      patients who sustain a first unprovoked venous thromboembolic event, which
      largely stems from our current inability to reliably identify those patients most
      likely to develop recurrences. Given that an individualized approach is required
      in deciding the duration of anticoagulation, it is the author's belief that low
      intensity warfarin, which the PREVENT trial demonstrated could be monitored every
      other month, is a useful option for some patients with a first episode of VTE.

PMID- 15461621
TI  - Randomized comparison of dexamethasone combined with melphalan versus melphalan
      with prednisone in the treatment of elderly patients with multiple myeloma.
AB  - Melphalan-prednisone (MP) has been the gold standard treatment for more than 30
      years in elderly multiple myeloma (MM) patients. In order to assess whether the
      combination of dexamethasone with melphalan (MD) could improve on the efficacy of
      MP, we have carried out a randomized trial comparing both treatment approaches. A
      total of 201 patients >/=70 years old were included in the study. The overall
      response rate was similar after six cycles (MP: 67.9%versus MD: 64.5%) and after
      12 cycles (MP: 49.4%versus MD: 46.1%). However, the proportion of complete
      responses (CR) was higher in the MD arm, particularly after 12 cycles (MD:
      22.4%versus MP: 9.1%; P < 0.05). There was no significant difference in event
      free survival (MP: 15.9 months versus MD: 23.3 months). The median overall
      survival in both arms was almost identical (MP: 29.4 months versus MD: 27.2
      months; P = 0.63). No significant differences in haematological toxicity were
      observed, but non-haematological toxicity was significantly higher in the MD arm.
      According to these results MP remains as the gold standard for treatment of MM
      and should be the reference for comparison of new therapeutic approaches
      involving novel agents.

PMID- 15461622
TI  - A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma.
AB  - In a phase 2 open-label study of the novel proteasome inhibitor bortezomib, 54
      patients with multiple myeloma who had relapsed after or were refractory to
      frontline therapy were randomized to receive intravenous 1.0 or 1.3 mg/m(2)
      bortezomib twice weekly for 2 weeks, every 3 weeks for a maximum of eight cycles.
      Dexamethasone was permitted in patients with progressive or stable disease after
      two or four cycles respectively. Responses were determined using modified
      European Group for Blood and Marrow Transplantation criteria. The complete
      response (CR) + partial response (PR) rate for bortezomib alone was 30% [90%
      confidence interval (CI), 15.7-47.1] and 38% (90% CI, 22.6-56.4) in the 1.0
      mg/m(2) (8 of 27 patients) and 1.3 mg/m(2) (10 of 26 patients) groups
      respectively. The CR + PR rate for patients who received bortezomib alone or in
      combination with dexamethasone was 37% and 50% for the 1.0 and 1.3 mg/m(2)
      cohorts respectively. The most common grade 3 adverse events were
      thrombocytopenia (24%), neutropenia (17%), lymphopenia (11%) and peripheral
      neuropathy (9%). Grade 4 events were observed in 9% (five of 54 patients).
      Bortezomib alone or in combination with dexamethasone demonstrated therapeutic
      activity in patients with multiple myeloma who relapsed after frontline therapy.

PMID- 15461623
TI  - Intravascular lymphoma: clinical presentation, natural history, management and
      prognostic factors in a series of 38 cases, with special emphasis on the
      'cutaneous variant'.
AB  - Despite its recognition as a distinct, extremely rare entity, no large studies of
      intravascular lymphoma (IVL) have been reported. The clinico-pathological
      characteristics of 38 human immunodeficiency virus-negative patients with IVL
      diagnosed in Western countries were reviewed to better delineate clinical
      presentation, clinical variants, natural history and optimal therapy. The IVL is
      an aggressive and usually disseminated disease (Ann Arbor stage IV in 68% of
      cases) that predominantly affects elderly patients (median age 70 years, range:
      34-90; male:female ratio 0.9), resulting in poor Eastern Cooperative Oncology
      Group Performance Status (ECOG-PS >1 in 61%), B symptoms (55%), anaemia (63%) and
      high serum lactate dehydrogenase level (86%). The brain and skin are the most
      common sites of disease. In contrast to previous reports, hepatosplenic
      involvement (26%) and bone marrow infiltration (32%) were found to be common
      features in IVL, while nodal disease was confirmed as rare (11% of cases).
      Patients with disease limited to the skin ('cutaneous variant'; 26% of cases)
      were invariably females with a normal platelet count, and exhibited a
      significantly better outcome than the remaining patients, which deserves further
      investigation. Overall survival was usually poor; however, the early use of
      intensive therapies could improve outcome in young patients with unfavourable
      features. ECOG-PS >1, 'cutaneous variant', stage I and chemotherapy use were
      independently associated with improved survival.

PMID- 15461624
TI  - Expression of two type 2N von Willebrand disease mutations identified in exon 18
      of von Willebrand factor gene.
AB  - Type 2N von Willebrand disease (VWD) is characterized by a markedly decreased
      affinity of von Willebrand factor (VWF) for factor VIII (FVIII). The FVIII
      binding site has been localized within the first 272 amino acid residues of
      mature VWF, encoded by exons 18-23. Two substitutions in exon 18 of VWF gene,
      inducing candidate mutations Y795C and C804F were identified in the heterozygous
      state in two French patients who also displayed the frequent R854Q mutation in
      exon 20. Expression studies in Cos-7 cells showed that these abnormalities, which
      implicate cysteine residues, induced secretion, multimerization and FVIII binding
      defects of corresponding recombinant VWF. Results from transfection experiments
      with R854Q, performed to reproduce the hybrid VWF present in patient plasma, were
      in agreement with those obtained for patient's plasma VWF. These findings confirm
      the importance of the VWF D' domain in FVIII binding. In addition, this work
      shows that exon 18 should preferentially be sequenced in type 2N VWD patients
      when the frequent R854Q mutation in exon 20 has been excluded or detected in the
      heterozygous state.

PMID- 15461625
TI  - Mutations within the protein Z-dependent protease inhibitor gene are associated
      with venous thromboembolic disease: a new form of thrombophilia.
AB  - Protein Z-dependent protease inhibitor (ZPI) is a serpin that inhibits the
      activated coagulation factors X and XI. The precise physiological significance of
      ZPI in the control of haemostasis is unknown although a deficiency of ZPI may be
      predicted to alter this balance. The coding region of the ZPI gene was screened
      for mutations using denaturing high-performance liquid chromatography. 16
      mutations/polymorphisms within the coding region of ZPI were identified including
      two mutations, which generated stop codons at residues R67 and W303. We observed
      nonsense mutations within the ZPI gene in 4.4% of thrombosis patients (n = 250)
      compared with 0.8% of controls (n = 250). The difference in distribution of stop
      codon mutations between thrombosis patients and controls was significant (P =
      0.02) with an odds ratio of 5.7 (95% confidence interval, 1.25-26.0). Our results
      suggest an association between ZPI deficiency and venous thrombosis and we
      propose that ZPI deficiency is potentially a new form of thrombophilia.

PMID- 15461626
TI  - Ex vivo evaluation of erythrocytosis-enhanced platelet thrombus formation using
      the cone and plate(let) analyzer: effect of platelet antagonists.
AB  - Red blood cells (RBC) contribute significantly to haemostasis and thrombosis
      under oscillatory flow conditions, and erythrocytosis has been associated with
      increased thrombotic risk. To measure the dynamic influences of RBC on platelets,
      we used a recently described cone and plate(let) analyzer (CPA), evaluating the
      effect of haematocrit (Hct) on platelet function in whole blood under arterial
      flow conditions (1800/s, 2 min, 25 degrees C). Anticoagulated blood,
      reconstituted to varying haematocrits with autologous RBC, demonstrated a
      significant increase in adherent platelet aggregate formation at Hct levels >45%.
      This increase was not affected by pretreatment of blood with 0.05 mmol/l aspirin,
      but was prevented by antagonists of P2Y1, P2Y12, or P2X1, ADP and ATP receptors,
      and by converting exogenous ADP to ATP with creatine phosphate/creatine
      phosphokinase. As negligible platelet granule secretion was measured during CPA
      analysis, but metabolic inhibition of RBC with sodium azide or glutaraldehyde
      fixation inhibited erythrocytosis-enhanced increases in platelet aggregate size,
      adenine nucleotides contributing to shear-induced platelet aggregate formation
      appear to be derived from erythrocytes. These findings support the use of CPA for
      ex vivo evaluation of the contribution of RBC to platelet function and its
      inhibition under physiological shear conditions.

PMID- 15461627
TI  - The effects of folic acid supplements on coagulation status in pregnancy.
AB  - Thromboembolic disease remains the leading cause of maternal death in the UK.
      Recent literature has proposed that folate status is a strong predictor for
      venous thrombosis. Using thrombelastography (TEG((R))), we tested the hypothesis
      that folic acid supplementation is associated with a reduction in whole blood
      coagulability. Blood samples and questionnaire data were obtained at a mean
      gestation of 13.6 weeks (SD: 3.8, range: 6-38 weeks) from unselected consecutive
      women attending for their antenatal booking scan. Of 588 patients, 439 (74.7%)
      took folic acid. All TEG((R)) parameters were less hypercoagulable in women that
      had taken folic acid compared with those that had not: mean maximum amplitude
      (MA) 60.3 versus 62.1; mean difference 1.8; 95% confidence interval 0.8, 2.8; P =
      0.0001; mean coagulation index (CI) 0.54 versus 0.85; mean difference 0.31; 95%
      confidence interval 0.11, 0.5; P = 0.002. There was no difference in the
      incidence of the homozygous MTHFR mutation in patients taking folic acid (5.53%)
      compared with those that were not (4.08%). This study suggests that benefit may
      be derived from longer-term treatment, although large multicentre studies are
      required to determine whether the relative hypocoagulability is associated with a
      reduction in risk of venous thrombosis.

PMID- 15461628
TI  - Acquired Glanzmann's thrombasthenia without thrombocytopenia: a severe acquired
      autoimmune bleeding disorder.
AB  - Acquired Glanzmann's thrombasthenia (GT) is an uncommon accompaniment to immune
      thrombocytopenic purpura. Rarely, GT may present as an acquired autoimmune
      disorder of platelet function, with rapid onset of a moderate-to-severe bleeding
      tendency, a prolonged bleeding time, but with a normal platelet count and normal
      platelet glycoprotein (GP) expression. This is caused by an autoantibody with
      specificity for platelet GP IIb/IIIa or an epitope close to that of the GP,
      resulting in partial or complete refractoriness of the patient's platelets to
      ADP, collagen and arachidonic acid. We describe two patients with acquired GT and
      a normal platelet count, who presented with severe bleeding. The first patient
      responded gradually to immunosuppressive treatment but eventually developed non
      Hodgkin's lymphoma. The second patient had no other underlying conditions and
      remitted spontaneously within 2 years.

PMID- 15461629
TI  - PRV-1, erythroid colonies and platelet Mpl are unrelated to thrombosis in
      essential thrombocythaemia.
AB  - Females with the monoclonal type of essential thrombocythaemia (ET), based on the
      X-chromosome inactivation pattern (XCIP), have previously been shown to present a
      higher incidence of thrombosis than polyclonal ones. We aimed to assess
      correlations between XCIP, thrombosis, and three epigenetic markers of ET, namely
      PRV-1 overexpression, endogenous erythroid colony (EEC) formation, and reduced
      platelet Mpl content. Fifty-three (60%) of 88 subjects studied had monoclonal
      myelopoiesis and presented a 32% incidence of major thrombosis compared with 6%
      of polyclonal subjects (P = 0.009). The frequency of abnormalities of PRV-1, EEC,
      or Mpl was similar in monoclonal and polyclonal subjects (respectively, 28%, 48%,
      75%, and 37%, 27%, 63%), and none of them correlated with thrombosis. We conclude
      that the exploited epigenetic markers constitute independent phenotypic
      variations and are not clustered according to monoclonality of myelopoiesis in
      ET; none of them could serve as a surrogate marker of thrombotic risk in male
      subjects with ET.

PMID- 15461630
TI  - Severe prekallikrein deficiency associated with homozygosity for an Arg94Stop
      nonsense mutation.
AB  - An elderly patient with no abnormal bleeding presented with prolongation of the
      activated partial thromboplastin time (aPTT). Preincubation of plasma with aPTT
      reagent caused shortening of the abnormal clotting time. Plasma prekallikrein
      (PK) activity and antigen were <5 u/dL. Molecular analysis showed a homozygous
      Arg94Stop substitution in the PK gene, predicted to prevent expression of the
      mutant allele. The five heterozygous offspring of the proband each showed a
      normal aPTT but reduced PK activity and antigen. This is the first description of
      a kindred in which absence of expression of one or both PK alleles has been
      confirmed by genotype.

PMID- 15461631
TI  - Hemojuvelin (HJV) mutations in persons of European, African-American and Asian
      ancestry with adult onset haemochromatosis.
AB  - Mutations in the chromosome 1q-linked gene hemojuvelin (HJV) have recently been
      found to be a cause of juvenile haemochromatosis. We addressed the question of
      whether hemojuvelin mutations may influence the phenotype of patients with adult
      onset haemochromatosis with or without mutations of the HFE gene. We sequenced
      the complete coding region of 133 subjects with iron overload. To screen a large
      number of patients, we also developed conditions for analysis by denaturing high
      performance liquid chromatography (dHPLC). This diagnostic modality detects many
      mutations of the HJV gene. One patient with severe iron overload was found to be
      a compound heterozygote for HJV mutations, one of which had previously been
      identified in patients with juvenile haemochromatosis (G320V) and the other was
      novel (C321W). A number of other mutations were identified, but none were clearly
      associated with increases in the body iron burden. Notable among these was a DNA
      triplet insert, predicting an insertion of glycine, found in two African-American
      subjects, one with and one without iron storage disease.

PMID- 15461633
TI  - Bone marrow examination in obese patients: CAT or not to CAT!

PMID- 15461632
TI  - Haemostasis.com: clinical experiences in the investigational use of rFVIIa in the
      management of severe haemorrhage.

PMID- 15461635
TI  - Severe cutaneous papillomavirus disease after haematopoietic stem-cell
      transplantation in patients with severe combined immunodeficiency.

PMID- 15461636
TI  - Lumbar puncture in thrombocytopenic children.

PMID- 15461638
TI  - Validating PCR for detecting invasive aspergillosis.

PMID- 15461639
TI  - Down-regulation of BCL-2 and its prevention by interleukin-4 in cultured chronic
      lymphocytic leukaemia cells is a methodological artefact caused by failure of
      protein detection/extraction following the onset of cell death.

PMID- 15461640
TI  - Fludarabine, cytosine arabinoside, granulocyte-colony stimulating factor with or
      without idarubicin in the treatment of high risk acute leukaemia or
      myelodysplastic syndromes.

PMID- 15461642
TI  - Abstracts of the European Sleep Research Society. Prague, Czech Republic. 2004.

PMID- 15461643
TI  - Psychological size and distance: a step towards better defining the human
      elements critical to learning.

PMID- 15461644
TI  - New approaches to learning clinical skills.

PMID- 15461645
TI  - Of course you don't mind being seen by the students.

PMID- 15461646
TI  - Self-reflection on the quality of decisions in health care.

PMID- 15461647
TI  - The effect of outcome information on doctors' evaluations of their own diagnostic
      decisions.
AB  - BACKGROUND: Outcome bias is a psychological tendency to use outcome information
      in order to evaluate the quality of a previous decision, where decisions with bad
      outcomes are undervalued and decisions with good outcomes are overvalued. In some
      circumstances, being affected by outcome when evaluating a diagnostic decision
      might have important educational consequences: bad diagnostic decisions
      resulting, by chance, in good outcomes might be repeated in the future, whilst
      good diagnostic decisions with bad outcomes might be abandoned. However, no
      previous studies have tested whether outcome bias affects doctors' evaluations of
      their own diagnostic decisions. METHODS: A total of 91 practising Italian doctors
      (69 general practitioners, 22 neurologists) chose a diagnosis for a neurological
      case and then evaluated it after receiving outcome information (positive outcome,
      adverse outcome or no outcome). RESULTS: Outcome information affected the doctors
      in many ways: the quality of the decision was overrated following good outcomes,
      and underrated following bad outcomes; the difficulty of making the diagnosis was
      underrated after good outcomes and overrated after bad outcomes, and the memory
      of weightings assigned to signs and symptoms consistent with the diagnosis was
      overrated after good outcomes and underrated after bad outcomes (and vice versa
      for the weighting of evidences inconsistent with the diagnosis). CONCLUSIONS:
      Outcome bias in medical decisions is discussed in terms of its possible adverse
      effects on doctors' learning and knowledge revision processes: although
      sensitivity to outcomes may be desirable in some circumstances, in other
      circumstances it can cause either the fixing of incorrect knowledge or the
      improper revision of correct knowledge.

PMID- 15461648
TI  - The role of encapsulated knowledge in clinical case representations of medical
      students and family doctors.
AB  - BACKGROUND: Previous studies on the development of medical expertise,
      predominantly using measures of free recall and pathophysiological explanations,
      have shown ambiguous results concerning the relationship between expertise level
      and encapsulated knowledge. PURPOSE: To investigate differences in clinical case
      representations by medical students and family doctors. In particular, the role
      of encapsulated knowledge in clinical case representations was investigated.
      METHODS: Year 2 (n = 15) and Year 4 (n = 15) medical students and family doctors
      (n = 15) were instructed to study carefully 2 case descriptions associated with a
      particular disease. After each case description participants were asked to
      provide a diagnosis. Subsequently, they judged whether or not a target item
      presented on a computer screen was related to the case description. Target items
      consisted of literally stated signs and symptoms, inferred encapsulated items and
      filler items. RESULTS: Family doctors provided more accurate diagnoses than Year
      2 and Year 4 medical students. Furthermore, family doctors were faster and made
      fewer errors in judging the relatedness of all item types than Year 2 and 4
      medical students. In particular, family doctors showed their best performance on
      the encapsulated items. CONCLUSIONS: The present study showed that encapsulated
      knowledge becomes increasingly more prominent as expertise develops. For
      experienced doctors, encapsulated concepts function as the most important
      building blocks of clinical case representations.

PMID- 15461649
TI  - The effects of deliberate practice in undergraduate medical education.
AB  - INTRODUCTION: Ericsson and colleagues introduced the term 'deliberate practice'
      to describe training activities that are especially designed to maximise
      improvement. They stressed that how much one practises is as important as how one
      practises. Essential aspects of deliberate practice are the presence of well
      defined tasks, informative feedback, repetition, self-reflection, motivation and
      endurance. Deliberate practice is often difficult, laborious, and even
      unpleasant. Previous studies in the fields of sports and music have shown a
      positive relation between deliberate practice and level of expertise. PURPOSE:
      The present study investigated the relationship between several aspects of
      deliberate practice and study achievements among undergraduate medical students.
      METHODS: A questionnaire was developed to measure important aspects of deliberate
      practice. It was filled out by 777 medical students at Maastricht University
      Medical School (response rate 90%). Scores on 3 regular tests were used to define
      student levels of expertise. RESULTS: Positive correlations between aspects of
      deliberate practice (self-study, study resources, planning, study style and
      motivation) and study achievements were found. Furthermore, high achieving
      students showed more characteristics of deliberate practice than low achieving
      students. CONCLUSION: Some important aspects of deliberate practice appear to
      contribute to the performance of medical students.

PMID- 15461650
TI  - Psychological size and distance: emphasising the interpersonal relationship as a
      pathway to optimal teaching and learning conditions.
AB  - BACKGROUND: Positive interpersonal relationships between teachers and learners
      increase the quality of learning. The purpose of this study was to investigate
      psychological size (perceived status) and psychological distance (perceived
      emotional connectedness) in medical teaching interactions and their impact on the
      teaching and learning process. METHOD: A total of 45 paediatric
      preceptor/resident pairs engaged in longitudinal continuity training experiences
      at different sites were surveyed about teaching effectiveness, satisfaction with
      teaching, and the psychological size and distance in the relationship between
      each pair. RESULTS: Both residents and preceptors perceived the resident as
      having a smaller psychological size compared to the preceptor. Residents
      perceived greater psychological distance in the relationship than did preceptors,
      and this distance was significantly related to both residents' satisfaction with
      particular preceptors and their perception of the preceptors' effectiveness.
      CONCLUSIONS: Psychological size and distance contribute to effective and
      satisfactory teaching. Investigating additional aspects of the teaching-learning
      relationship should help identify optimal educational conditions.

PMID- 15461651
TI  - Interpreting course evaluation results: insights from thinkaloud interviews with
      medical students.
AB  - PURPOSE: To determine whether some of the fundamental assumptions that frequently
      underlie interpretation of course evaluation results are justified by
      investigating what medical students are thinking as they complete a typical basic
      science course evaluation. METHODS: A total of 24 students participated in
      thinkaloud cognitive interviews, voicing their thoughts while completing a
      typical evaluation instrument that included items on overall course design,
      educational materials and methods, and faculty teaching. Students' responses were
      organised to consider how they interpreted questions, formed judgements and
      selected response options. Major themes relevant to the meaningful interpretation
      of course evaluation data were identified. RESULTS: Medical students understood
      educational terms such as 'independent learning' in different ways from both one
      another and common usage. When formulating responses, students' judgements were
      sometimes based on unique or unexpected criteria, and they described editing
      their judgements by considering factors such as effort or caring on the part of
      teaching faculty. Students tended to avoid using the lower end of the rating
      scale, used the highest rating option selectively, but chose the second highest
      category indiscriminately. CONCLUSIONS: These results call into question
      fundamental assumptions that frequently underlie interpretation of course
      evaluation results, such as whether students understand the intended meanings of
      terms used in items; whether faculty members who receive the same rating are
      perceived similarly; whether ratings actually reflect teaching effectiveness, and
      whether 'positive' ratings reflect positive opinions. This study also
      demonstrates how thinkaloud interviews can be used in validity studies, providing
      information to supplement statistical and psychometric analyses.

PMID- 15461652
TI  - The patient as text: a challenge for problem-based learning.
AB  - OBJECTIVES: To explore the values and assumptions underlying problem-based
      learning (PBL) cases through narrative analysis, in order to consider the ways by
      which paper cases may affect student attitudes and values. METHODS: Randomly
      chosen PBL cases from the first year curriculum at Dalhousie University medical
      school (n = 10) were coded by 3 independent reviewers attending to narrative
      components. RESULTS: The cases generally used spare, objective language, used the
      passive voice, eliminated agency, and employed linguistic markers to encode
      scepticism about patient reports. There was almost no sense of the presence of
      the patient as person in these cases in terms of their words, feelings, or their
      social and cultural context. The almost complete exclusion of the preferences and
      priorities of the patient was striking. CONCLUSION: The sample is small, the
      results only suggestive. Yet it appears that the cases used in PBL may
      unnecessarily, even unintentionally, encourage student detachment from the
      messiness of real patients' lives and emotions. Positioning a particular way of
      seeing - the doctor's gaze - as normative renders less visible the choices that
      are being made whenever an account is constructed. Including multiple voices in a
      case would complicate that tidy reduction of choices. Ongoing attempts to enrich
      the case format should be encouraged. At the same time, students may benefit from
      being taught the skills for critical analysis of the case itself.

PMID- 15461653
TI  - Comparison of computer-assisted instruction (CAI) versus traditional textbook
      methods for training in abdominal examination (Japanese experience).
AB  - PURPOSE: This study aimed to compare the effects of computer-assisted, text-based
      and computer-and-text learning conditions on the performances of 3 groups of
      medical students in the pre-clinical years of their programme, taking into
      account their academic achievement to date. A fourth group of students served as
      a control (no-study) group. METHOD: Participants were recruited from the pre
      clinical years of the training programmes in 2 medical schools in Japan, Jichi
      Medical School near Tokyo and Kochi Medical School near Osaka. Participants were
      randomly assigned to 4 learning conditions and tested before and after the study
      on their knowledge of and skill in performing an abdominal examination, in a
      multiple-choice test and an objective structured clinical examination (OSCE),
      respectively. Information about performance in the programme was collected from
      school records and students were classified as average, good or excellent.
      Student and faculty evaluations of their experience in the study were explored by
      means of a short evaluation survey. RESULTS: Compared to the control group, all 3
      study groups exhibited significant gains in performance on knowledge and
      performance measures. For the knowledge measure, the gains of the computer
      assisted and computer-assisted plus text-based learning groups were significantly
      greater than the gains of the text-based learning group. The performances of the
      3 groups did not differ on the OSCE measure. Analyses of gains by performance
      level revealed that high achieving students' learning was independent of study
      method. Lower achieving students performed better after using computer-based
      learning methods. CONCLUSION: The results suggest that computer-assisted learning
      methods will be of greater help to students who do not find the traditional
      methods effective. Explorations of the factors behind this are a matter for
      future research.

PMID- 15461654
TI  - Performance-related stress symptoms in simulated patients.
AB  - INTRODUCTION: During the first 4 years of the 6-year undergraduate medical
      curriculum at Maastricht University, the Netherlands, students practise clinical
      skills in simulated patient (SP) encounters at the Skillslab. Generally, these
      encounters are instructive and enjoyable for both students and SPs. However, in
      conversations with SP trainers, some SPs have mentioned experiencing adverse
      symptoms due to performing a patient role. Some published studies have reported
      similar findings in SPs. We explored the seriousness of this problem by surveying
      SPs on the occurrence and severity of stress symptoms related to performing
      patient roles. We also examined by which variables the symptoms were influenced.
      METHODS: An anonymous questionnaire was developed to investigate factors related
      to stress symptoms and the frequency and severity of stress symptoms. A burnout
      scale was also included in the questionnaire. All SPs who had performed between
      March 2000 and March 2001 were asked to participate. RESULTS: The response rate
      was 84%. Of the SPs, 73% were found to have experienced stress symptoms, with a
      mean of 4 symptoms per SP. No significant correlations were found between the
      occurrence of symptoms on the one hand and factors that might influence symptoms
      or the burnout scale on the other hand. DISCUSSION: An unexpectedly high number
      of SPs reported symptoms. Fortunately, the symptoms were relatively mild (2.2 on
      a 5-point scale). Future studies should address the connection between work as an
      SP and symptoms, and measures should be taken to prevent and treat the symptoms.
      Debriefing sessions might play a role in this respect.

PMID- 15461655
TI  - Simulation and clinical practice: strengthening the relationship.
AB  - INTRODUCTION: This discussion paper argues for a creative synthesis between
      simulation and clinical practice, where an iterative process of continual
      interaction ensures that skills are learned and reinforced within the context of
      everyday professional life. BACKGROUND: Evidence is mounting that long
      established approaches to surgical training are no longer acceptable in the
      current ethical and professional climate. This paper considers alternatives to
      the traditional approach of 'learning by doing' in a clinical context, focusing
      on recent developments in the technology of simulation and virtual reality.
      Clinical expertise is a complex phenomenon and no single theory can account for
      its acquisition. After a brief contextualising overview, Vygotsky's 'zone of
      proximal development' is proposed as a conceptual framework for task-based
      surgical learning that takes place within skills laboratories. The discussion is
      located within a wider context of educational theory, drawing on current thinking
      about situated learning and apprenticeship. The notion of 'legitimate peripheral
      participation' in a complex professional environment places technical skill
      alongside a range of other competencies that are necessary to safe practice.
      CONCLUSIONS: Simulation offers a safe environment within which learners can
      repeatedly practise a range of clinical skills without endangering patients.
      Comprehensive simulated environments allow a move away from isolated tasks to
      more complex clinical situations, recreating many of the challenges of real life.
      Such simulations, however, can operate in isolation from their clinical context,
      ignoring the learning needs of individuals within a real health care environment.
      To realise its full potential as a learning aid, simulation must be used
      alongside clinical practice and linked closely with it.

PMID- 15461656
TI  - Assessing undergraduate palliative care education: validity and reliability of
      two scales examining perceived efficacy and outcome expectancies in palliative
      care.
AB  - BACKGROUND: Medical students have traditionally received little education in
      palliative care. However, in 1999, as part of a revised medical curriculum, Year
      4 undergraduates at Liverpool University participated in a 2-week programme of
      education in palliative care. To assess the effect of the education programme, 2
      assessment scales were identified: the Self-efficacy in Palliative Care Scale
      (SEPC) (assessing efficacy in communication, patient management and
      multiprofessional teamworking) and the Thanatophobia Scale (assessing attitudes
      towards palliative care). The aim of this study was to examine the psychometric
      properties of these scales. METHODS: The scales were examined by 5 palliative
      care doctors for content validity and appropriate wording. Following this, the
      SEPC and Thanatophobia Scales were completed by the undergraduates (n = 139)
      prior to and after completion of the education programme. RESULTS: Both scales
      were analysed independently on pre- and post-test scores. Cronbach's alphas of
      0.84-0.85 and 0.92-0.95 were recorded, respectively, indicating high reliability.
      Varimax rotated principal components analysis of the SEPC Scale suggested 3
      distinct factors, as theoretically expected, with high factor loadings of 0.45
      0.89 at pre- and post-test. Principal components analysis of the Thanatophobia
      Scale suggested only 1 factor underlies the scale, as theoretically expected. All
      7 items had high factor loadings of 0.60-0.81 at pre- and post-test. CONCLUSIONS:
      The results suggest that the SEPC and Thanatophobia Scales are valid and reliable
      assessment scales that may be of use when evaluating the impact of an education
      programme.

PMID- 15461657
TI  - Comprehensive undergraduate medical assessments improve prediction of clinical
      performance.
AB  - OBJECTIVES: This study aimed to compare an essay-style undergraduate medical
      assessment with modified essay, multiple-choice question (MCQ) and objective
      structured clinical examination (OSCE) undergraduate medical assessments in
      predicting students' clinical performance (predictive validity), and to determine
      the relative contributions of the written (modified essay and MCQ) assessment and
      OSCE to predictive validity. DESIGN: Before and after cohort study. SETTING: One
      medical school running a 6-year undergraduate course. PARTICIPANTS: Study
      participants included 137 Year 5 medical students followed into their trainee
      intern year. MAIN OUTCOME MEASURES: Aggregated global ratings by senior doctors,
      junior doctors and nurses as well as comprehensive structured assessments of
      performance in the trainee intern year. RESULTS: Students' scores in the new
      examinations predicted performance significantly better than scores in the old
      examinations, with correlation coefficients increasing from 0.05-0.44 to 0.41
      0.81. The OSCE was a stronger predictor of subsequent performance than the
      written assessments but combining assessments had the strongest predictive
      validity. CONCLUSION: Using more comprehensive, more reliable and more authentic
      undergraduate assessment methods substantially increases predictive validity.

PMID- 15461658
TI  - Portfolios for assessment of paediatric specialist registrars.
AB  - INTRODUCTION: In 1997 the Royal College of Paediatrics and Child Health
      introduced portfolios to guide and monitor the learning of specialist registrars.
      We studied their value for assessment. METHODS: Using Bigg's SOLO criteria we
      devised a marking scheme based on 6 domains of competence: clinical,
      communication, teaching and learning, ethics and attitudes, management and
      evaluation, and creation of evidence. We rated portfolios according to quality of
      evidence presented and expectations by year of training. We similarly assessed
      trainee performance in the annual record of in-training assessment (RITA)
      interview. Specific advice based on the results of the first portfolio
      assessments was circulated to all trainees, instructing them to increase the
      structure and decrease the bulk of portfolios. A second sample of portfolios was
      reviewed a year later, using similar evaluations, to determine the effects.
      RESULTS: A total of 76 portfolios were assessed in year 1 by a single rater; 30
      portfolios were assessed in year 2 by 2 independent raters. The quality of
      documentation improved from year 1 to year 2 but there was no significant
      increase in portfolio scores. The inter-rater correlation coefficient of the
      portfolio assessment method was 0.52 (Cohen's kappa 0.35). The inter-rater
      correlation coefficient of the RITA interview was 0.71 (Cohen's kappa 0.38).
      There was moderate inter-assessment correlation between portfolios and RITA
      interviews (kappa 0.26 in year 1 and 0.29 in year 2). Generalisability analysis
      suggested that 5 successive ratings by a single observer or independent ratings
      by 4 observers on the same occasion would be needed to yield a generalisability
      coefficient > 0.8 for overall portfolio rating. CONCLUSIONS: This method of
      portfolio assessment is insufficiently reliable as a sole method for high stakes,
      single-instance assessment, but has a place as part of a triangulation process.
      Repeated portfolio assessment by paired observers would increase reliability.
      Longer term studies are required to establish whether portfolio assessment
      positively influences learner behaviour.

PMID- 15461659
TI  - Structural basis for distinct roles of Lys63- and Lys48-linked polyubiquitin
      chains.
AB  - Ubiquitination, a modification in which single or multiple ubiquitin molecules
      are attached to a protein, serves as a signalling function that controls a wide
      variety of cellular processes. To date, two major forms of polyubiquitin chain
      have been functionally characterized, in which the isopeptide bond linkages
      involve Lys48 or Lys63. Lys48-linked polyubiquitin tagging is mostly used to
      target proteins for degradation by the proteasome, whereas Lys63-linked
      polyubiquitination has been linked to numerous cellular events that do not rely
      on degradative signalling via the proteasome. Apparently linkage-specific
      conformations of polyubiquitin chains are important for these cellular functions,
      but the structural bases distinguishing Lys48- and Lys63-linked chains remain
      elusive. Here, we report NMR and small-angle X-ray scattering (SAXS) studies on
      the intersubunit interfaces and conformations of Lys63- and Lys48-linked di- and
      tetraubiquitin chains. Our results indicate that, in marked contrast to Lys48
      linked chains, Lys63-linked chains are elongated molecules with no stable non
      covalent intersubunit interfaces and thus adopt a radically different
      conformation from that of Lys48-linked chains.

PMID- 15461660
TI  - A cryptic lysis gene near the start of the Qbeta replicase gene in the +1 frame.
AB  - The maturation/lysis (A2) protein encoded by the group B single-stranded RNA
      bacteriophage Qbeta mediates lysis of host Escherichia coli cells. We found a
      frameshift mutation in the replicase (beta-subunit) gene of Qbeta cDNA causes
      cell lysis. The mutant has a single base deletion 73 nucleotides (nt) 3' from the
      start of the replicase gene with consequent translation termination at a stop
      codon 129-131 nt further 3'. The 43-amino acid C-terminal part of the 67-amino
      acid product encoded by what in WT (wild-type) is the +1 frame, is rich in basic
      amino acids This 67-aa protein can mediate cell lysis whose characteristics
      indicate that the protein may cause lysis by a different mechanism and via a
      different target, than that caused by the A2 maturation/lysis protein. Synthesis
      of a counterpart of the newly discovered lysis product in wild-type phage
      infection would require a hypothetical ribosomal frameshifting event. The lysis
      gene of group A RNA phages is also short, 75 codons in MS2, and partially
      overlaps the first part of their equivalently located replicase gene, raising
      significant evolutionary implications for the present finding.

PMID- 15461661
TI  - Local exposure of phosphatidylethanolamine on the yeast plasma membrane is
      implicated in cell polarity.
AB  - Cell surface phosphatidylethanolamine (PE) of the yeast cell was probed by
      biotinylated Ro09-0198 (Bio-Ro), which specifically binds to PE and was
      visualized with fluorescein-labelled streptavidin. In Saccharomyces cerevisiae,
      the signals were observed at the presumptive bud site, the emerging small bud
      cortex, the bud neck of the late mitotic large-budded cells and the tip of the
      mating projection. In Schizosaccharomyces pombe, the signals were observed at one
      end or both ends of mono-nucleated cells and the division plane of the late
      mitotic cells. These sites were polarized ends in the yeast cells, implying that
      PE is exposed on the cell surface at cellular polarized ends. Treatment of S.
      cerevisiae cells with Ro09-0198 resulted in aberrant F-actin accumulation at the
      above sites, implying that limited surface exposure of PE is involved in the
      polarized organization of the actin cytoskeleton. Furthermore, S. cerevisiae
      ros3, dnf1 and dnf2 null mutants, which were known to be defective in the
      internalization of fluorescence-labelled PE, as well as the combinatorial
      mutants, were stained with Bio-Ro at the enlarging bud cortex, in addition to the
      Bio-Ro-staining sites of wild-type cells, suggesting that Ros3p, Dnf1p and Dnf2p
      are involved in the retrieval of exposed PE at the bud cortex.

PMID- 15461662
TI  - DNA topoisomerase II is required for the G0-to-S phase transition in Drosophila
      Schneider cells, but not in yeast.
AB  - We previously reported that DNA topoisomerase II (topo II) is required for the
      G(0)-to-S phase transition in mammalian cells [Hossain et al. (2002) ICRF-193, a
      catalytic inhibitor of DNA topoisomerase II, inhibits re-entry into the cell
      division cycle from quiescent state in mammalian cells. Genes Cells 7, 285-294].
      In this study, we examined whether the requirement for topo II is evolutionarily
      conserved in Drosophila and yeast. ICRF-193, a catalytic inhibitor of topo II,
      inhibited DNA synthesis in Drosophila Schneider cells released from the G(0)
      (stationary) phase, whereas the drug did not inhibit DNA synthesis in Schneider
      cells released from the M phase. Depletion of topo II mRNA by RNA-interference
      (RNAi) in G(0)-phase Schneider cells resulted in significant inhibition of DNA
      synthesis after release from G(0)-arrest. In the yeast topo II temperature
      sensitive (ts) mutant, the initial cycle of DNA synthesis occurred at a
      restrictive temperature after release from starvation-induced G(0) phase and
      doubling of the DNA content in the cells was confirmed by both flow cytometry and
      fluorescence spectrophotometry. DNA synthesis in yeast cells after release from
      the G(0) phase was also observed in the presence of ICRF-193. Doubling of the DNA
      content was observed during spore germination of topo II ts mutant yeast at a
      restrictive temperature as determined by fluorescence spectrophotometry. These
      results indicate that topo II is required for the G(0)-to-S phase transition in
      Drosophila Schneider cells, but not in yeast.

PMID- 15461663
TI  - Characterization of multiple transcripts and isoforms derived from the mouse
      protein tyrosine phosphatase gene Ptprr.
AB  - The use of alternative splice sites, promoters and translation start sites
      considerably adds to the complexity of organisms. Four mouse cDNAs (PTPBR7, PTP
      SL, PTPPBSgamma+ and PTPPBSgamma-) have been cloned that contain different 5'
      parts but encode identical protein tyrosine phosphatase PTPRR catalytic domains.
      We investigated the genomic origin and coding potential of these transcripts to
      elucidate their interrelationship. Mouse gene Ptprr exons were identified within
      a 260 kbp segment on chromosome 10, revealing PTP-SL- and PTPPBSgamma-specific
      transcription start sites within introns two and four, respectively, relative to
      the 14 PTPBR7 exons. Northern and RT-PCR analyses demonstrated differential
      expression patterns for these promoters. Furthermore, transfection studies and
      AUG codon mutagenesis demonstrated that in PTP-SL and PTPPBSgamma messengers
      multiple translation initiation sites are being used. Resulting 72, 60, 42 and 37
      kDa PTPRR protein isoforms differ not only in the length of their N-terminal part
      but also in their subcellular localization, covering all major PTP subtypes;
      receptor-like, membrane associated and cytosolic. In summary, mouse gene Ptprr
      gives rise to multiple isoforms through the use of distinct promoters,
      alternative splicing and differential translation starts. These results set the
      stage for further investigations on the physiological roles of PTPRR proteins.

PMID- 15461664
TI  - DREF is required for EGFR signalling during Drosophila wing vein development.
AB  - The DNA replication-related element binding factor (DREF) has been suggested as
      being involved in regulation of DNA replication- and proliferation-related genes
      in Drosophila. Recently, by searching the Drosophila genome database, we also
      found DRE-like sequences in the 5'-flanking regions of many genes with other
      functions. In addition, immunostaining of polytene chromosomes with an anti-DREF
      monoclonal antibody revealed that DREF can bind to a hundred regions of polytene
      chromosomes, suggesting regulation of multiple genes and multiple roles in vivo.
      When we over-expressed DREF protein or inverted repeat RNA of the DREF gene in
      wing imaginal discs using the GAL4-UAS targeted expression system in Drosophila,
      the results were veins of increased width and a loss of veins, respectively. With
      DREF over-expression, Rolled, a Drosophila MAPK homologue, was ectopically
      activated. Furthermore, half reduction of the D-raf gene dose suppressed this
      DREF-induced vein of increased width phenotype. In addition, when DREF
      transcripts were reduced by introducing double-stranded RNA of the DREF gene into
      S2 cells, the D-raf gene promoter activity was diminished to 4%. These data
      indicate that DREF is involved in regulation of vein formation through the
      activation of EGFR signalling in the Drosophila wing imaginal discs.

PMID- 15461665
TI  - Propagation of gammaPKC translocation along the dendrites of Purkinje cell in
      gammaPKC-GFP transgenic mice.
AB  - To elucidate spatial and temporal profiles of the protein kinase C (PKC)
      activation in relation to neuronal functions including synaptic plasticity, we
      tried to detect PKC translocation in living brain slices. We first developed
      brain region-specific and inducible gammaPKC-GFP transgenic mice using a
      tetracycline (tet)-regulated system. In the transgenic mice, the expression of
      gammaPKC-GFP was region-specifically regulated by the promoter and abolished by
      the administration of doxycycline. Cerebellar slices from the mice were utilized
      for intracellular recording and fluorescence imaging of gammaPKC-GFP in Purkinje
      cells. GFP fluorescence was uniformly distributed from soma to dendritic arbor.
      When mGluR agonists were applied, the intensity was transiently increased at the
      edge of the dendrite and concomitantly decreased in the cytoplasm, indicating
      that gammaPKC translocated to the plasma membrane. This transient change in the
      pattern of GFP fluorescence simultaneously occurred throughout the Purkinje cell
      dendrites by agonist stimulation. Translocation of gammaPKC-GFP was also induced
      by electrical stimulation of parallel fibres. However, the event was not
      restricted at the distal dendrites, propagated forwardly along the dendritic tree
      and reached to the proximal trunk close to the soma. Time course of the
      propagation was slower than the electrical signal and Ca(2+) waves and faster
      than conveying molecules through microtubules. The present results indicate that
      PKC signals activated locally by parallel fibre input could propagate to the soma
      through dendrites in living Purkinje neurones. The findings may provide us with a
      new insight for understanding molecular mechanisms of the synaptic plasticity
      including cerebellar long-term depression.

PMID- 15461666
TI  - SR proteins preferentially associate with mRNAs in the nucleus and facilitate
      their export to the cytoplasm.
AB  - Different classes of RNA are exported to the cytoplasm by distinct mechanisms.
      Each class of RNA forms distinct complexes with nuclear proteins prior to its
      export to the cytoplasm. In our attempt to obtain comprehensive information of
      protein factors that specifically associate with mRNAs in the nucleus, we
      performed in vivo UV-crosslinking analysis after microinjection of various RNAs
      into Xenopus oocyte nucleus. We found a group of proteins preferentially
      crosslinked to mRNAs. Immunoprecipitation experiments revealed that some of the
      crosslinked signals corresponded to SR (serine/arginine-rich) proteins, a family
      of essential RNA-binding proteins involved in pre-mRNA splicing. It was
      previously suggested that some members of SR protein family are involved in
      export of a specific intronless mRNA, histone H2A mRNA and some spliced mRNAs.
      However, it is still to be clarified if SR proteins are involved in export of
      general mRNAs, especially general intronless mRNAs that do not contain specific
      RNA export elements. When we microinjected an antibody against SR proteins into
      the nucleus, export of mRNAs was severely inhibited, regardless of whether the
      mRNAs were produced via pre-mRNA splicing or not, whereas export of other RNAs
      was not affected. These results unequivocally showed that SR proteins are
      involved in export of both general intronless and spliced mRNAs.

PMID- 15461667
TI  - Harp (harmonin-interacting, ankyrin repeat-containing protein), a novel protein
      that interacts with harmonin in epithelial tissues.
AB  - Mutations in the triple PDZ domain-containing protein harmonin have been
      identified as the cause of Usher deafness syndrome type 1C. Independently, we
      identified harmonin in a screen for genes expressed in pancreatic beta cells.
      Using a yeast two-hybrid assay, we show that the first PDZ domain of harmonin
      interacts with a novel protein, designated harp for harmonin-interacting, ankyrin
      repeat-containing protein. This interaction was confirmed in an over-expression
      system and in mammalian cells, and shown to be mediated by the three C-terminal
      amino acids of harp. Harp is expressed in many of the same epithelia as harmonin
      and co-localization of native harp and harmonin was demonstrated by confocal
      microscopy in pancreatic duct epithelium and in a pancreatic beta-cell line.
      Harp, predicted molecular mass 48 kDa, has a domain structure which includes
      three ankyrin repeats and a sterile alpha motif. Human harp maps to chromosome
      16, and its mouse homologue to chromosome 7. Sequences with similarity to harp
      include the sans gene, mutations of which are responsible for deafness in the
      Jackson shaker 2 (js) mutant mouse and in human Usher syndrome type 1G. The
      functional domain structures of harp and harmonin, their interaction under native
      conditions and their co-localization suggest they constitute a scaffolding
      complex to facilitate signal transduction in epithelia.

PMID- 15461668
TI  - In vivo potentiation of human oestrogen receptor alpha by Cdk7-mediated
      phosphorylation.
AB  - Phosphorylation of the Ser(118) residue in the N-terminal A/B domain of the human
      oestrogen receptor alpha (hERalpha) by mitogen-activated protein kinase (MAPK),
      stimulated via growth factor signalling pathways, is known to potentiate ERalpha
      ligand-induced transactivation function. Besides MAPK, cyclin dependent kinase 7
      (Cdk7) in the TFIIH complex has also been found to potentiate hERalpha
      transactivation in vitro through Ser(118) phosphorylation. To investigate an
      impact of Cdk7 on hERalpha transactivation in vivo, we assessed activity of
      hERalpha in a wild-type and cdk7 inactive mutant Drosophila that ectopically
      expressed hERalpha in the eye disc. Ectopic expression of the wild-type or mutant
      receptors, together with a green fluorescent protein (GFP) reporter gene, allowed
      us to demonstrate that hERalpha expressed in the fly tissues was
      transcriptionally functional and adequately responded to hERalpha ligands in the
      patterns similar to those observed in mammalian cells. Replacement of Ser(118)
      with alanine in hERalpha (S118A mutant) significantly reduced the ligand-induced
      hERalpha transactivation function. Importantly, while in cdk7 inactive mutant
      Drosophila the wild-type hERalpha exhibited reduced response to the ligand;
      levels of transactivation by the hERalpha S118A mutant were not affected in these
      inactive cdk7 mutant flies. Furthermore, phosphorylation of hERalpha at Ser(118)
      has been observed in vitro by both human and Drosophila Cdk7. Our findings
      demonstrate that Cdk7 is involved in regulation of the ligand-induced
      transactivation function of hERalphain vivo via Ser(118) phosphorylation.

PMID- 15461669
TI  - XXVIth International Congress of the World Federation of Hemophilia. Bangkok,
      Thailand, 17-21 October 2004. Abstracts.

PMID- 15461670
TI  - Navigating toward fetal and maternal health: the challenge of treating epilepsy
      in pregnancy.
AB  - A rational approach to the treatment of women of childbearing potential with
      epilepsy has been hampered by the lack of conclusive data on the comparative
      teratogenic potential of different antiepileptic drugs (AEDs). Although, several
      cohort studies on birth defects associated with AED use during pregnancy have
      been published, these have generally failed to demonstrate differences in
      malformation rates between AEDs, probably mainly due to insufficient power. In
      particular, pregnancies with new generation AEDs have been too few. In recent
      years, pregnancy registries have been introduced to overcome this problem--EURAP
      (an international collaboration), the North American, and the U.K. AED and
      pregnancy registries are observational studies that prospectively assess
      pregnancy outcome after AED exposure using slightly different methods. Each has
      enlisted 3-5,000 pregnancies in women with epilepsy, and the North American and
      the U.K. have released preliminary observations. Thus the U.K. registry reported
      a higher malformation rate with valproate, 5.9% (4.3-8.2%; 95% CI), than with
      carbamazepine, 2.3% (1.4-3.7%), and lamotrigine, 2.1% (1.0-4.0%). Most of the
      more recent cohort studies have also identified a nonsignificant trend toward a
      higher teratogenicity with valproate. These signals need to be interpreted with
      some caution since none of the studies to date have fully assessed the impact of
      possible confounders, such as type of epilepsy, family history of birth defects,
      etc. However, with increasing number of pregnancies it should be possible in the
      near future for the pregnancy registries to take such confounding factors into
      account and thus make more reliable assessments of the causal relationship
      between exposure to specific AEDs and teratogenic risks. While awaiting more
      conclusive results, it appears reasonable to be cautious in prescribing valproate
      to women considering to become pregnant if other suitable treatment alternatives,
      and with less teratogenic potential, are available. Any attempt to change
      treatment should, however, be accomplished well before conception. The importance
      of maintained seizure control must also be kept in mind, and the woman who needs
      valproate to control her seizures should not be discouraged from pregnancy,
      provided that counseling at the best of available knowledge is given.

PMID- 15461671
TI  - Isobolographic and subthreshold analysis of interactions among felbamate and four
      conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice.
AB  - PURPOSE: Despite possibility of idiosyncratic reaction development, felbamate
      (FBM) is recommended in Lennox-Gastaut syndrome and partial refractory epilepsy.
      The aim of this study was to evaluate the profile of interactions between FBM and
      four conventional antiepileptic drugs (AEDs): clonazepam (CZP), ethosuximide
      (ESM), phenobarbital (PB), and valproate (VPA), in pentylenetetrazole (PTZ)
      induced convulsions in mice, a model of myoclonic seizures in humans. METHODS:
      Data obtained from PTZ-evoked seizures were compared by use of two basic
      procedures, the subthreshold method and isobolographic analysis. Results of the
      chimney test (evaluating motor coordination) also were elaborated
      isobolographically. Thus it was possible to determine both median toxic dose
      (TD50) and protective index (PI) for each drug combination. RESULTS: FBM reduced
      the clonic seizure activity [with an ED50 of 9.7 mg/kg; TD50, 439.1 mg/kg; and
      PI, 45.3]. FBM at the dose of 10 mg/kg, but not 7.5 mg/kg, significantly reduced
      PTZ-induced convulsions in mice. In the subthreshold method, FBM (7.5 mg/kg) did
      not affect the protective activity of conventional AEDs used in the study.
      However, when applied at 10 mg/kg, it enhanced the protective activity of PB and
      ESM, but not that of VPA or CZP. The nature of these interactions could not be
      precisely estimated with this method. The exact profile of drug interactions was
      determined with the use of isobolography. In terms of seizure inhibition,
      antagonism was found between FBM and VPA applied at the fixed-dose ratio of 3:1.
      Synergy was detected between FBM and PB (1:3). Combinations of FBM with VPA (1:3,
      1:1), PB (1:1, 3:1), and ESM or CZP (1:3, 1:1, 3:1) led to additive interactions.
      As regards motor impairment, the combinations of FBM with VPA (1:3) or CZP (1:1,
      3:1) were synergistic. Remaining combinations exhibited pure additivity.
      Pharmacokinetic events may influence FBM/ESM and FBM/CZP interactions, because
      FBM lowered the brain concentration of ESM and increased that of CZP.
      CONCLUSIONS: The profitable benefit index was found only for the combination of
      FBM with PB (1:3). Conversely, the combinations of FBM with either VPA (1:3) or
      CZP (1:1, 3:1) do not seem promising for the therapy of refractory myoclonic
      convulsions. Isobolographic analysis provides more reliable clues to be
      considered by the clinicians willing to introduce AED combinations for the
      therapy of epilepsy.

PMID- 15461672
TI  - Selective antiepileptic effects of N-palmitoylethanolamide, a putative
      endocannabinoid.
AB  - PURPOSE: The purpose of this study was to determine whether N
      palmitoylethanolamide (PEA), a putative endocannabinoid, would be effective
      against kindled amygdaloid seizures. For a comparison with earlier work, we also
      tested the effectiveness of PEA against pentylenetetrazol (PTZ)-induced
      convulsions. METHODS: Kindling electrodes were implanted bilaterally in the
      amygdala in 32 Long-Evans rats. After the kindling of generalized (stage 5)
      seizures, the effects of PEA administration [i.p.; 1, 10, 100 mg/kg in
      dimethylsulfoxide (DMSO)] were evaluated for anticonvulsant activity. PEA (40
      mg/kg, i.p. in DMSO) also was tested for anticonvulsant activity against PTZ
      induced convulsions (75 mg/kg, i.p.). RESULTS: After i.p. administration of PEA,
      kindled rats displayed an increased latency to clonus at the 1-mg/kg dose. No
      other dose-dependent effects were noted. When tested against PTZ-induced
      convulsions, PEA protected against tonic convulsions and prolonged the latency
      between convulsive episodes. CONCLUSIONS: PEA produces antiepileptic effects, but
      does not completely suppress seizures. The mechanism of action of PEA remains to
      be defined.

PMID- 15461673
TI  - Calcium extrusion protein expression in the hippocampal formation of chronic
      epileptic rats after kainate-induced status epilepticus.
AB  - PURPOSE: The plasma membrane Ca2+ -adenosine triphosphatase (ATPase) (PMCA) and
      (potassium-dependent) sodium-calcium exchange [NC(K)X] represent two main calcium
      extrusion mechanisms that are important for the restoration of [Ca2+]i levels
      after electrical activity. We investigated whether the expression of these
      calcium-extrusion proteins is altered in the course of epileptogenesis. METHODS:
      Hippocampal-parahippocampal protein expression of NCX1, 2, and 3, PMCA1-4, and
      NCKX2 at an early and late stage after kainate-induced status epilepticus (SE)
      was compared with that in control rats by using immunocytochemistry. RESULTS:
      Several alterations were found in chronic epileptic rats: (a) NCX1 expression was
      permanently decreased in the inner molecular layer (IML) of the dentate gyrus
      (DG) and entorhinal cortex layer III (ECIII), related to neuronal loss in hilus
      and ECIII, respectively; (b) PMCA and NCKX2 expression was transiently
      upregulated in the IML, and decreased in several areas where cell loss had
      occurred, (c) NCX3 expression, which in control rats is abundant in presynaptic
      terminals of mossy fibers (MF), was extensively and permanently decreased in
      stratum lucidum and hilar region. In addition, newly formed MF sprouts that
      project to the DG iml did not noticeably express NCX3; (d) NCX2 and NCKX2 were
      (transiently) upregulated in astrocytes of epileptic rats throughout the
      hippocampal formation, including ECIII. CONCLUSIONS: These region-specific
      changes in calcium-extrusion proteins reflect a change in calcium regulation.
      Whether these regional-specific changes of calcium-extrusion proteins are
      associated with an abnormal calcium homeostasis must be determined. Because some
      alterations of calcium-extrusion protein expression are already present at an
      early stage of epileptogenesis, they could be involved in this process.

PMID- 15461674
TI  - Mitochondrial dysfunction and ultrastructural damage in the hippocampus during
      kainic acid-induced status epilepticus in the rat.
AB  - PURPOSE: Prolonged and continuous epileptic seizure (status epilepticus) results
      in cellular changes that lead to neuronal damage. We investigated whether these
      cellular changes entail mitochondrial dysfunction and ultrastructural damage in
      the hippocampus, by using a kainic acid (KA)-induced experimental status
      epilepticus model. METHODS: In Sprague-Dawley rats maintained under chloral
      hydrate anesthesia, KA (0.5 nmol) was microinjected unilaterally into the CA3
      subfield of the hippocampus to induce seizure-like hippocampal EEG activity. The
      activity of key mitochondrial respiratory chain enzymes in the dentate gyrus
      (DG), or CA1 or CA3 subfield of the hippocampus was measured 30 or 180 min after
      application of KA. Ultrastructure of mitochondria in those three hippocampal
      subfields during KA-induced status epilepticus also was examined with electron
      microscopy. RESULTS: Microinjection of KA into the CA3 subfield of the
      hippocampus elicited progressive build-up of seizure-like hippocampal EEG
      activity. Enzyme assay revealed significant depression of the activity of
      nicotinamide adenine dinucleotide cytochrome c reductase (marker for Complexes
      I+III) in the DG, or CA1 or CA3 subfields 180 min after KA-elicited temporal lobe
      status epilepticus. Conversely, the activities of succinate cytochrome c
      reductase (marker for Complexes II+III) and cytochrome c oxidase (marker for
      Complex IV) remained unaltered. Discernible mitochondrial ultrastructural damage,
      varying from swelling to disruption of membrane integrity, also was observed in
      the hippocampus 180 min after hippocampal application of KA. CONCLUSIONS: Our
      results demonstrated that dysfunction of Complex I respiratory chain enzyme and
      mitochondrial ultrastructural damage in the hippocampus are associated with
      prolonged seizure during experimental temporal lobe status epilepticus.

PMID- 15461675
TI  - Epilepsy and synaptic reorganization in a perinatal rat model of hypoxia
      ischemia.
AB  - PURPOSE: One of the potential consequences of perinatal hypoxia-ischemia (H-I) is
      the development of epilepsy, and synaptic reorganization in the hippocampus has
      been associated with epilepsy after an injury. We tested the hypothesis that
      perinatal H-I will induce spontaneous motor seizures, hippocampal lesions, and
      synaptic reorganization in the dentate gyrus. METHODS: The right common carotid
      artery of 7-day-old rats was permanently ligated, and the rats were placed for
      120 min into a chamber filled with 8% oxygen (37 degrees C). Animals were
      directly observed for chronic motor seizures for 7 to 24 months after the H-I
      insult. RESULTS: Nearly half of the rats (i.e., eight of 20) were seen to have
      spontaneous motor seizures after the H-I injury. The ipsilateral hippocampi from
      both the rats with seizures and the rats not seen to have seizures had
      hippocampal lesions and increased amounts of Timm stain in the inner molecular
      layer (IML) compared with controls. The contralateral hippocampi from the rats
      with seizures, but not the hippocampi from the rats not seen to have seizures,
      had significantly increased amounts of Timm stain in the IML. CONCLUSIONS: These
      results suggest that perinatal H-I can induce epilepsy, ipsilateral hippocampal
      lesions, and mossy fiber sprouting in the lesioned and contralateral hippocampus.

PMID- 15461676
TI  - Aging alters electroencephalographic and clinical manifestations of kainate
      induced status epilepticus.
AB  - PURPOSE: The elderly exhibit an increased risk for developing status epilepticus
      and status-related morbidity and mortality. However, it is unclear how aging
      alters the progression of electroencephalographic (EEG) activity and behavioral
      manifestations during status epilepticus. METHODS: A repetitive low-dose kainate
      treatment protocol (2.5 mg/kg/h; i.p.) was used in this study in conjunction with
      EEG and behavioral monitoring from freely behaving adult (7-8 months) and aged
      (22-25 months) Fischer 344 rats to assess the effects of aging on status
      epilepticus. RESULTS: During kainate treatment, both groups exhibited an increase
      in EEG power that corresponded with the time course of kainate treatment.
      However, visual inspection and spectral analysis revealed a reduction of the
      faster frequencies (12.5-35 Hz) in the EEGs of aged rodents. A similar
      progression of behavioral manifestations was observed in adult and aged rodents
      during kainate treatment, although the frequency of preseizure manifestations
      (e.g., wet-dog shakes; aged rats, 110 events/h vs. adults, 25 events/h; median
      values) was greater, and latency to onset for any given behavioral manifestation
      (e.g., class V seizures; aged median, 60 min, vs. adult median, 145 min) was
      consistently shorter within the aged group. CONCLUSIONS: These data reveal that
      aged Fischer 344 rats exhibit altered EEG activity (reduction of higher
      frequencies) and clinical manifestations during kainate-induced status
      epilepticus. Taken together, these data indicate an age-related change in seizure
      onset and spread after exposure to glutamate analogues.

PMID- 15461677
TI  - Anticonvulsant efficacy of the low-affinity partial benzodiazepine receptor
      agonist ELB 138 in a dog seizure model and in epileptic dogs with spontaneously
      recurrent seizures.
AB  - PURPOSE: Ataxia, sedation, amnesia, ethanol and barbiturate potentiation, loss of
      efficacy (tolerance), development of dependence, and the potential for drug abuse
      limit the clinical use of benzodiazepines (BZDs) for long-term treatment of
      epilepsy or anxiety. BZD ligands that are in current use act as full allosteric
      modulators of gamma-aminobutyric acid (GABA)-gated chloride channels and, on long
      term administration, trigger a functional uncoupling between the GABAA and BZD
      recognition sites. Partial allosteric modulators, which have a low intrinsic
      activity at the BZD recognition site of the GABAA receptor, might eventually
      overcome the limitations of full agonists such as diazepam (DZP). METHODS: In the
      present study, the new low-affinity partial BZD-receptor agonist ELB 138 [former
      name AWD 131-138; 1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one] was evaluated
      in a dog seizure model and in epileptic dogs with spontaneously recurrent
      seizures. RESULTS: ELB 138 was shown to increase potently the pentylenetetrazole
      (PTZ) seizure threshold in dogs. Prolonged oral administration with twice-daily
      dosing of ELB 138 with either 5 or 40 mg/kg over a 5-week period was not
      associated with loss of anticonvulsant efficacy in the PTZ dog model. To study
      whether physical dependence developed during long-term treatment, the BZD
      antagonist flumazenil was injected after 5 weeks of treatment with ELB 138.
      Compared with prolonged treatment with DZP, only relatively mild abstinence
      symptoms were precipitated in dogs treated with ELB 138, particularly at the
      lower dosage (5 mg/kg, b.i.d.). In a prospective trial in dogs with newly
      diagnosed epilepsy, ELB 138 markedly reduced seizure frequency and severity
      without significant difference to standard treatments (phenobarbital or
      primidone) but was much better tolerated than the standard drugs. In dogs with
      chronic epilepsy, most dogs exhibited a reduction in seizure frequency and
      severity during add-on treatment with ELB 138. CONCLUSIONS: The data demonstrate
      that the partial BZD receptor agonist ELB 138 exerts significant anticonvulsant
      efficacy without tolerance in a dog seizure model as well as in epileptic dogs
      with spontaneously recurrent seizures. These data thus substantiate that partial
      agonism at the BZD site of GABAA receptors offers advantages versus full agonism
      and constitutes a valuable approach for treatment of seizures.

PMID- 15461678
TI  - fMRI of generalized absence status epilepticus in conscious marmoset monkeys
      reveals corticothalamic activation.
AB  - PURPOSE: A nonhuman primate model of generalized absence status epilepticus was
      developed for use in functional magnetic resonance imaging (fMRI) experiments to
      elucidate the brain mechanisms underlying this disorder. METHODS: Adult male
      marmoset monkeys (Callithrix jacchus) were treated with gamma-butyrolactone (GBL)
      to induce prolonged absence seizures, and the resulting spike-wave discharges
      (SWDs) were analyzed to determine the similarity to the 3-Hz SWDs that
      characterize the disorder. In addition, blood-oxygenation-level-dependent (BOLD)
      fMRI was measured at 4.7 Tesla after absence seizure induction with GBL. RESULTS:
      Electroencephalographic recordings during imaging showed 3-Hz SWDs typical of
      human absence seizures. This synchronized EEG pattern started within 15 to 20 min
      of drug administration and persisted for >60 min. In addition, pretreatment with
      the antiepileptic drug, ethosuximide (ESM), blocked the behavioral and EEG
      changes caused by GBL. Changes in BOLD signal intensity in the thalamus and
      sensorimotor cortex correlated with the onset of 3-Hz SWDs. The change in BOLD
      signal intensity was bilateral but heterogeneous, affecting some brain areas more
      than others. No significant negative BOLD changes were seen. CONCLUSIONS: The
      BOLD fMRI data obtained in this marmoset monkey model of absence status
      epilepticus shows activation within the thalamus and cortex.

PMID- 15461679
TI  - Dynamic cortical activity during spasms in three patients with West syndrome: a
      multichannel near-infrared spectroscopic topography study.
AB  - PURPOSE: To investigate spatial and temporal cortical activity during clusters of
      naturally occurring epileptic spasms in patients with West syndrome (WS) by using
      multichannel near-infrared spectroscopy (mNIRS). METHODS: Conventional magnetic
      resonance imaging (MRI) and interictal and ictal single-photon emission computed
      tomography (SPECT) were carried out in three patients with WS. Thereafter,
      cortical hemodynamics during naturally occurring epileptic spasms were measured
      by mNIRS with simultaneous video/electroencephalographic (EEG) monitoring.
      RESULTS: Ictal SPECT revealed multiple hyperperfused areas within the cortex.
      With the use of mNIRS, an increase in regional cerebral blood volume (CBV) was
      observed in these areas, which is representative of cortical activation. The
      increase in CBV was accompanied by an increase in the concentrations of both oxy-
      and deoxyhemoglobin. The following heterogeneous regional changes in CBV during
      ictus were observed: (a) transient increases that were synchronized with spasms;
      (b) a gradual increase during an ictal event that fluctuated in synchrony with
      spasms; and (c) a combination of transient and gradual increases. An increase in
      regional CBV occurred in multiple areas that were activated either simultaneously
      or sequentially during an ictal event. Topographic changes in CBV were closely
      correlated with the phenotype of the spasm. CONCLUSIONS: During ictal events,
      multiple cortical areas were activated simultaneously or sequentially. The
      pattern of cortical activation closely affected the phenotype of the spasm, which
      suggested that the cortex was involved in the generation of spasms.

PMID- 15461680
TI  - Autosomal dominant early childhood seizures associated with chondrocalcinosis and
      a mutation in the ANKH Gene.
AB  - We describe the pattern of early childhood seizures within a family with
      autosomal dominant chondrocalcinosis (CCAL, which causes adult-onset arthritis).
      All affected family members with CCAL experienced seizures in early childhood,
      usually, but not always, associated with fever. Similarities exist to the
      syndrome of generalized epilepsy with febrile seizures plus (GEFS+). A mutation
      within the ANKH gene on chromosome 5p has been found previously in this family;
      other patients with familial CCAL (but without seizures) have mutations in the
      same gene. ANKH codes for a transmembrane protein involved in the regulation of
      extracellular pyrophosphate ion levels, although its precise mechanism of action
      remains unclear. It is highly expressed in the brain, and its expression may be
      influenced by seizure activity. The mutation within this family creates a
      premature initiation codon, adding four amino acids to the N-terminus of the
      protein. We postulate that this may lead to a gain of function, causing seizure
      susceptibility as well as chondrocalcinosis. Mutations within this gene may
      underlie other forms of genetic epilepsy and febrile seizures.

PMID- 15461682
TI  - Psychopathology and pediatric complex partial seizures: seizure-related,
      cognitive, and linguistic variables.
AB  - PURPOSE: This study examined the role of cognition, language, seizure-related,
      and demographic variables in the psychopathology of children with complex partial
      seizure disorder (CPS) of average intelligence. METHODS: One-hundred one CPS and
      102 normal children, aged 5.1 to 16.9 years, had a structured psychiatric
      interview and cognitive and language testing. Parents provided demographic,
      perinatal, and seizure-related information, as well as behavioral information
      through the Child Behavior Checklist (CBCL) and a structured psychiatric
      interview about the child. RESULTS: Significantly more CPS patients had
      psychopathology, cognitive deficits, and linguistic deficits than did those in
      the normal group. Among the patients, Verbal IQ predicted the presence of a
      psychiatric diagnosis, as well as CBCL scores in the borderline/clinical range.
      Seizure, linguistic, and demographic variables were unrelated to psychopathology.
      The cognitive and linguistic deficits of the CPS group, however, were predicted
      by seizure factors (e.g., prolonged seizures/febrile convulsions; seizure
      frequency/number of antiepileptic drugs) and demographic factors (e.g., minority
      status). CONCLUSIONS: Because subtle verbal cognitive deficits predict behavioral
      disturbances in pediatric CPSs, the study's findings highlight the importance of
      assessing behavior, cognition, and language in these children. They also
      underscore the negative impact of prolonged seizures, febrile convulsions,
      seizure frequency, and antiepileptic drug polytherapy on cognition and language
      in pediatric CPSs.

PMID- 15461681
TI  - Neuropsychological predictors of academic underachievement in pediatric epilepsy:
      moderating roles of demographic, seizure, and psychosocial variables.
AB  - PURPOSE: Academic underachievement is common in pediatric epilepsy. Attempts to
      identify seizure and psychosocial risk factors for underachievement have yielded
      inconsistent findings, raising the possibility that seizure and psychosocial
      variables play a complex role in combination with other variables such as
      neuropsychological functioning. This study cross-validated a neuropsychological
      measurement model for childhood epilepsy, examined the relation between
      neuropsychological functioning and academic achievement, and tested the degree to
      which demographic, seizure, and psychosocial variables moderate that relation.
      METHODS: Children with chronic epilepsy (N = 173; ages 8 to 15 years; 49% girls;
      91% white/non-Hispanic; 79% one seizure type; 79% taking one medication; 69% with
      active seizures) completed a comprehensive neuropsychological battery. Children
      diagnosed with mental retardation were excluded. RESULTS: Structural equation
      modeling identified a three-factor measurement model of neuropsychological
      function: Verbal/Memory/Executive (VME), Rapid Naming/Working Memory (RN/WM), and
      Psychomotor (PM). VME and RN/WM were strongly related to reading, math, and
      writing; PM predicted writing only. Family environment moderated the impact of
      neuropsychological deficits on writing (p < or = 0.01) and possibly for reading
      (p = 0.05); neuropsychological deficits had a smaller impact on achievement for
      children in supportive/organized homes compared with children in
      unsupportive/disorganized homes. CONCLUSIONS: These findings lend partial support
      for our theoretical model showing direct effects of neuropsychological function
      on achievement and the moderating role of family factors. This study suggests
      that a subgroup of children with epilepsy (those who have not only
      neuropsychological deficits but also disorganized/unsupportive home environments)
      are particularly at risk for adverse academic outcomes. Implications for
      intervention are discussed.

PMID- 15461683
TI  - Worsening of seizures by oxcarbazepine in juvenile idiopathic generalized
      epilepsies.
AB  - PURPOSE: Several studies have shown that carbamazepine (CBZ) may aggravate
      idiopathic generalized epilepsy (IGE). Oxcarbazepine (OXC) is a new drug
      chemically related to CBZ. We report six cases of juvenile IGE with a clear
      aggravation by OXC. METHODS: We retrospectively studied all patients with IGE
      first referred to our epilepsy department between January 2001 and June 2003 and
      treated with OXC. RESULTS: During this period, six patients were identified. All
      had an aggravation of their epilepsy in both clinical and EEG activities. OXC had
      been used because of an incorrect diagnosis of focal epilepsy or generalized
      tonic-clonic seizures (GTCSs) of undetermined origin (no syndromic classification
      of the epilepsy). Before OXC, only one patient had experienced a worsening of
      seizures with an inadequate drug (CBZ). Four had juvenile myoclonic epilepsy, one
      had juvenile absence epilepsy, and one had IGE that could not be classified into
      a precise syndrome. OXC (dosage range, 300-1,200 mg/day) was used in monotherapy
      in all of them except for one patient. Aggravation consisted of a clear
      aggravation of myoclonic jerks (five cases) or de novo myoclonic jerks (one
      case). Three patients had exacerbation of absence seizures. One patient had
      worsened dramatically and had absence status, and one had de novo absences after
      OXC treatment. The effects of OXC on GTCSs were less dramatic, with no worsening
      in frequency in three and a slight increase in three. CONCLUSIONS: OXC can be
      added to the list of antiepileptic drugs that can exacerbate myoclonic and
      absence seizures in IGE.

PMID- 15461684
TI  - Successful management of intractable epilepsy with lidocaine tapes and continuous
      subcutaneous lidocaine infusion.
AB  - PURPOSE: We report the successful management of a 10-year-old girl with
      intractable frontal lobe epilepsy by using lidocaine tapes and continuous
      subcutaneous lidocaine infusion. METHODS: This patient's seizures were refractory
      to conventional antiepileptic drugs (AEDs) and mexiletine, but they responded
      well to the intravenous infusion of lidocaine. The intravenous infusion of
      lidocaine was replaced by lidocaine tape therapy, and subsequently by continuous
      subcutaneous lidocaine infusion therapy. The lidocaine tape (Penles, Nihon
      Lederle, Tokyo Japan) used was a stamp-sized (30.5 x 50.0 mm) tape containing 18
      mg of lidocaine. We used 25 lidocaine tapes every 12 h (50 tapes/day). Lidocaine
      hydrochloride (10%) was administered continuously at a dose of 1.5 mg/kg/h (0.3
      ml/hour) through a 27-G needle that was inserted in the subcutaneous tissue.
      RESULTS: Lidocaine tape therapy showed good efficacy for 1 year. After that, six
      lidocaine tapes were added 6 h after the exchange of 25 lidocaine tapes [62
      tapes/day (25,6,25,6)], because the seizures became frequent when the lidocaine
      tapes were being exchanged. The seizures were then well controlled, but
      dermatitis due to the lidocaine tapes grew serious, and lidocaine tape therapy
      had to be stopped. Continuous subcutaneous infusion of lidocaine applied in place
      of lidocaine tapes provided long-term seizure control without remarkable side
      effects. CONCLUSIONS: Lidocaine tape therapy and continuous subcutaneous
      lidocaine infusion therapy were considered to be useful for controlling this
      patient's seizures. This is the first report to describe the efficacy of
      continuous subcutaneous lidocaine infusion therapy for epilepsy.

PMID- 15461685
TI  - The prevalence of epilepsy in patients with celiac disease.
AB  - PURPOSE: The relation between celiac disease and epilepsy is uncertain. Previous
      studies have suggested an association, whereas others have not. METHODS: We
      ascertained the prevalence of active epilepsy in a cohort of 801 celiac patients
      by patient interviews and retrospective case note review. All the celiac patients
      had diagnostic confirmation by small bowel biopsy. RESULTS: Twenty-one patients
      had a history of epileptic seizures, but only nine (1.1%) had active epilepsy. No
      specific epileptic syndrome was identified. CONCLUSIONS: This study suggests that
      a causal relation between gluten sensitivity and active epilepsy is unlikely.

PMID- 15461686
TI  - Biparental inheritance in idiopathic generalized epilepsy.

PMID- 15461688
TI  - Getting research into practice.

PMID- 15461689
TI  - Falls risk assessment, multitargeted interventions and the impact on hospital
      falls.
AB  - There is an urgent need for inquiry to validate existing scales in the accurate
      assessment of falls risk. Moreover, where fall prevention projects have targeted
      specific risk factors of falling, such as cognitive impairment, few have measured
      the impact of their intervention on fall outcomes. A comparative design compared
      and described differences in falls data within and between two study cohorts
      before and after a multitargeted intervention was introduced. A cut-off score of
      > or = 50 using the Morse Scale was a good baseline indicator for accurate
      identification of fall risk and outcomes verify that the modified Morse Falls
      Scale, in combination with other risk factors, more accurately profiled fall risk
      among this population. Fall incidence among the intervention cohort did not
      increase significantly despite a rise in the number of hospital admissions and a
      significantly higher reported fall risk potential.

PMID- 15461690
TI  - Geriatric rehabilitation nursing: developing a model.
AB  - In this paper, we describe a geriatric rehabilitation nursing model developed on
      the basis of the nursing and rehabilitation literature. That literature comprised
      some 120 articles addressing the rehabilitation of elderly patients and the work
      done by nurses in that process, various philosophical questions and the results
      of geriatric rehabilitation. One-third of these articles has been evaluated on
      the strength of the articles' evidence, and these are discussed in this paper.
      The findings show that the main factors in geriatric rehabilitation nursing are
      the patient with health or functional problems and the nurse with professional
      values, knowledge and skills. The patient is part of a family and the nurse works
      as part of a multidisciplinary team. In the geriatric rehabilitation process, the
      patient and the nurse work in close interaction. The aims of rehabilitation
      depend upon the patient's commitment to the objective and upon the nurse's
      commitment to help the patient achieve that objective. A health orientation, goal
      oriented work, nursing decision-making and a rehabilitative approach to work are
      all central to this effort. Work is organized in multidisciplinary teams where
      nurses have equal responsibilities with other professional staff. Testing and
      development of the model is ongoing.

PMID- 15461691
TI  - Errors in body temperature assessment related to individual variation, measuring
      technique and equipment.
AB  - Errors in body temperature measurement might seriously influence the evaluation
      of an individual's health condition. We studied individual variation, measurement
      technique and the equipment used when assessing body temperature. In the first
      part of the study, three volunteers performed repeated measurements for five
      mornings. In the second part, the morning rectal, oral, ear and axillary
      temperatures were measured once in 84 men and women (19-59 years). The repeated
      measurements showed a daily temperature difference of 0.1-0.4 degrees C in rectal
      and oral temperatures, 0.2 degrees C-1.7 degrees C in the ear and 0.1-0.9 degrees
      C in the axillary temperatures. In the sample of 84 subjects, men and
      postmenopausal women had a lower mean body temperature compared to premenopausal
      women. The mean deviation between rectal temperature, and oral, ear and axillary
      temperatures, respectively, was > 0.5 degrees C, with a large individual
      variation. In conclusion, in order to improve the evaluation of body temperature,
      the assessment should be based on the individual variation, the same site of
      measurement and no adjustment of oral, ear or axillary temperatures to the rectal
      site.

PMID- 15461692
TI  - The effectiveness of a multidisciplinary pain management programme managing
      chronic pain.
AB  - The aim of this study was to develop and evaluate the effects of a
      multidisciplinary pain management programme on coping, health-related quality of
      life and pain intensity. Seventy-six outpatients suffering from chronic pain
      completed this eight-week programme with the primary aims to increase coping, as
      measured by the Ways of Coping Checklist, and health-related quality of life, as
      measured by the Short Form-36 Health Survey. Therapeutic dialogues and education,
      combined with physical activity, were given in order to increase understanding of
      and attention to non-medical factors that might affect pain perception. The
      programme was active, time-limited and structured on the basis of
      multidisciplinary pain management programmes based on a cognitive-behavioural
      approach. The findings suggest that this programme has the potential to improve
      coping skills and health-related quality of life. Additionally, pain intensity,
      as measured by the Visual Analogue Scale, was reduced. Age and disability were
      revealed as the prominent predictors of change after treatment. The differences
      in this sample indicated that the drop-outs tended to be older and reported more
      health problems, although these findings were non-significant. Clinical and
      research implications are discussed.

PMID- 15461693
TI  - Predictors of patients' experiences of nursing care in medical-surgical wards.
AB  - The purposes of this study were to explore patients' opinions of nursing care and
      to identify predictors of patients' experiences of nursing care in medical
      surgical wards. The sample of the study was 225 adult patients in medical
      surgical wards in a major teaching hospital in Jordan. The experiences of nursing
      care total score in this study was relatively high. The findings showed that the
      majority of the participants had positive experiences regarding the time nurses
      spent with them as well as the respect nurses provided to patients' relatives and
      friends. Although the amount of information nurses provided to patients was found
      to be a significant predictor of patients' experiences, the provided information
      was perceived by the majority of the patients as inadequate. Identifying factors
      that enhance patients' experiences of nursing care is crucial as it assists
      nurses to provide better care.

PMID- 15461694
TI  - Establishing prevention, education and community awareness through a
      comprehensive diabetes, hypertension and hypercholesterolaemia screening
      programme: The Smith Island, Maryland, USA experience.
AB  - Glucose screening is essential in providing early detection for diabetes.
      Screening for hypertension and hypercholesterolaemia in diabetics can help
      identify clients at an increased risk for morbidity and mortality. Free health
      screening clinics, which included components based on the ABCs of Diabetes, were
      set up on Smith Island, Maryland, USA in January 2001. An extensive health
      history was performed on each clinic attendee and baseline assessment data were
      collected. To date, 273 residents have been screened at the clinics. Clinic
      education adopted from the National Diabetes Education Program was provided to
      all attendees. This programme provided members of the community with a baseline
      assessment and general information on diabetes prevention, detection and
      treatment. Positive lifestyle strategies were introduced within the community.
      Barriers to future disease prevention were identified during the programme.

PMID- 15461696
TI  - PTH revisited.
AB  - Recent investigations of parathyroid hormone (PTH) have advanced our
      understanding of its circulating forms as well as its action. It is now clear
      that first-generation immunoradiometric assays of so-called intact "PTH" not only
      measured full-length PTH(1-84) but also recognized large PTH fragments lacking
      the amino-terminus. New, second generation assays detect only full-length PTH.
      Under diverse pathological settings, second generation assays display lower
      levels of PTH (1-84). By measuring full-length PTH (bioactive PTH) and the
      combined full-length plus amino-terminal PTH fragments, the amount of non-PTH(1
      84) in circulation can be estimated. The primary amino-terminal fragment is
      likely to be PTH(7-84). A considerable controversy surrounds the pathological
      significance of PTH(7-84) and its relation to adynamic bone disease. While these
      findings were emerging, other work uncovered the apparent basis by which PTH
      receptors signal through cAMP in some instances but through Ca/inositol phosphate
      in others. This signaling switch is dictated by the cytoplasmic adapter protein
      NHERF1 (EBP50), which is expressed in a cell-selective fashion. Other provocative
      findings may provide a means of unifying determinations of PTH(7-84) with the
      effects of NHERF1 on PTH receptor signaling. These latter studies reveal that in
      cells expressing NHERF1, PTH(7-84) has no effect on PTH receptor signaling or
      internalization. However, in cells lacking or expressing low levels of NHERF1,
      PTH(7-84) internalizes the PTH receptor without accompanying activation.
      Together, these findings suggest that the accumulation of PTH(7-84) in renal
      failure may lead to PTH resistance by internalizing and down-regulating PTH
      receptors.

PMID- 15461698
TI  - Renal water reabsorption: a physiologic retrospective in a molecular era.
AB  - The cloning and sequencing of the aquaporin water channels has been an enormous
      advance in the biomedical sciences, as recognized by the award of the Nobel Prize
      to Peter Agre last year. Among many other examples, expression of aquaporin
      proteins in Xenopus oocytes and other heterologous expression systems has
      confirmed two important models of renal function: the increase in the water
      permeability of the collecting duct by antidiuretic hormone (ADH), and the
      mechanism of near isosmotic volume reabsorption by the proximal tubule. These
      mechanisms were the subjects of intensive investigation by numerous
      investigators, including Thomas E. Andreoli, who is being honored by this
      symposium, and who developed many of the key concepts in these areas. His early
      work with artificial lipid bilayer membranes and the pore-forming antibiotic
      amphotericin provided the rigorous foundation in experimental and conceptual
      modeling techniques that he later applied to physiologic and pathophysiologic
      mechanisms in the kidney, which are summarized in this retrospective. Dr.
      Andreoli and his colleagues proposed a water channel mechanism for the action of
      ADH, which has been confirmed by the cloning and heterologous expression of
      aquaporin-2. They also proposed that volume reabsorption by the proximal tubule
      depended on a very high hydraulic conductivity and the development of luminal
      hypotonicity produced by active solute reabsorption. This model has also been
      confirmed in mice in which aquaporin-1 expression is knocked out, resulting in a
      low proximal tubule water permeability that exaggerates the development of
      luminal hypotonicity.

PMID- 15461699
TI  - Calcium and salinity sensing by the thick ascending limb: a journey from mammals
      to fish and back again.
AB  - The roles of the CaSR in endocrine, epithelial, CNS, and other cells have been
      reviewed previously [17-19, 20, 27-30, 31-33]. This brief review focuses on the
      roles of the CaSR in the thick ascending limb of Henle (TAL), and is written in
      honor of my mentor and long-term friend and colleague, Thomas E. Andreoli, on the
      occasion of his retirement. My early studies of TAL function with Tom Andreoli
      were the inspiration for this work.

PMID- 15461700
TI  - Romancing the macula densa at UAB.
AB  - The Nephrology Research and Training Center, established in 1977 at the
      University of Alabama at Birmingham by Thomas E. Andreoli, served as a catalyst
      to stimulate multiple areas of investigations in renal physiology and nephrology.
      Individuals with backgrounds in biophysics, membrane transport, renal
      hemodynamics, structural biology, and nephrology interacted with each other, thus
      providing an exciting and collegial environment. The laboratory of renal
      hemodynamics focused on the control of renal blood flow, glomerular filtration
      rate in normal and hypertensive models, and on the important role of the macula
      densa in providing communication from the tubules to the vascular elements.
      Studies initially focused on the role of the macula densa feedback mechanism in
      mediating renal autoregulatory behavior. Subsequent experiments examined various
      aspects of the feedback system, including the identification and characterization
      of membrane transport events that sense changes in tubular fluid concentration
      and transfer information to intracellular signaling mechanisms. More recent
      investigations have focused on the capability of the macula densa cells to
      synthesize and release various vasoactive mediators that can influence vascular
      tone of the glomerular arterioles. In particular, the ability of the macula densa
      cells to secrete ATP has stimulated continued interest in the hypothesis that ATP
      may serve an important role in mediating signals to afferent arteriolar vascular
      smooth muscle cells.

PMID- 15461702
TI  - Kinase-mediated transcription, activators of nongenotropic estrogen-like
      signaling (ANGELS), and osteoporosis: a different perspective on the HRT dilemma.
AB  - Studies in bone, as well as other nonreproductive target tissues of sex steroid,
      like the cardiovascular and the central nervous system (CNS), have elucidated a
      previously unappreciated mechanism of sex steroid action involving the rapid
      activation of mitogen-activated protein kinases and/or phosphatidyl inositol 3
      kinase, and consequent potent regulatory affects on the transcription of a set of
      genes that is distinct from that regulated through classic (genotropic) control
      of transcription. These actions stem from an unexpected function of the classic
      nuclear receptors outside the nucleus, most probably from receptor interactions
      within distinct signal transduction pathways in preassembled scaffolds.
      Importantly, these nongenotropic actions are mediated by the ligand-binding
      domain of the receptor and can be functionally dissociated from classic
      transcriptional activation with synthetic ligands, termed activators of
      nongenotropic estrogen-like signaling (ANGELS). We highlight this evidence and
      discuss its pharmacotherapeutic implications vis a vis the dilemmas posed by the
      recently appreciated shortfalls of postmenopausal hormone replacement therapy.

PMID- 15461703
TI  - Novel aspects in regulated expression of the renal type IIa Na/Pi-cotransporter.
AB  - Proximal tubular phosphate (P(i)) reabsorption is a key element in overall
      phosphate homeostasis; physiologic/pathophysiologic alterations are related to
      the control of brush border membrane expression (regulated endocytosis) of the
      type IIa sodium (Na)/phosphate(P(i))-cotransporter (NaPi-IIa). The carboxy
      terminus of NaPi-IIa contains sequences important for its apical
      delivery/expression; the last three amino acids are involved in PSD95/DglA/ZO-1
      (PDZ) interactions involving NaPi-IIa, Na/H exchanger-regulatory factor 1
      (NHERF1/2), and PDZK1/2 (apical scaffold). Regulated endocytosis of NaPi-IIa
      [e.g., parathyroid hormone (PTH)-induced] is reduced in megalin-deficient mice;
      internalization occurs via clathrin-coated structures, early endosomes, and
      finally leads to lysosomal degradation. NaPi-IIa contains, in the third
      intracellular loop, a sequence motif required for internalization. Different
      hormonal [e.g., PTH, atrial natriuretic peptide (ANP), also nitric oxide (NO)]
      and nonhormonal factors activate a variety of intracellular signaling cascades
      [protein kinase A (PK-A), protein kinase C (PK-C), protein kinase G (PK-G),
      extracellular receptor kinase (ERK)-1/2] leading (by unknown mechanisms) to NaPi
      IIa internalization. Different phosphatonins [e.g., fibroblast growth factor
      (FGF)-23, frizzled related protein (FRP)-4, matrix
      extracellularphosphoglycoprotein (MEPE)], associated with different
      pathophysiologic states of renal P(i)-handling, seem also to control apical
      expression of NaPi-IIa. Internalization of NaPi-IIa first requires its removal
      from the apical scaffold. This scaffold can also be considered as a regulatory
      scaffold containing also protein kinase A (PK-A)-anchoring proteins (AKAPs,
      ezrin) and the apical PTH receptor. The role of the different components of the
      regulatory scaffold in regulated endocytosis of NaPi-IIa is at present unknown.

PMID- 15461704
TI  - Oxidants and iron in chronic kidney disease.
AB  - Oxidants derived either from leukocytes in proliferative glomerular nephritis or
      from resident glomerular cells in nonproliferative glomerulonephritis have been
      shown to have several biologic effects relevant to chronic kidney disease. These
      include: the ability of oxidants to damage glomerular basement membrane (GBM) and
      to directly induce proteinuria; effects that would lead to a fall in the
      glomerular filtration rate; and effects that would account for the morphologic
      changes observed in chronic kidney disease. In experimental models the role of
      oxidants has been demonstrated in both proliferative glomerulonephritis (e.g.,
      anti-GBM antibody disease) as well as experimental models of minimal change
      disease and membranous nephropathy. Oxidants have also been shown to be an
      important mediator of the various pathways that have been implicated in diabetic
      nephropathy. Antioxidants and iron chelators have also been shown to retard
      functional and morphologic changes observed in progressive kidney disease. Taken
      together, these experimental studies suggest an important role of oxidants in
      chronic kidney disease.

PMID- 15461705
TI  - Inflammatory cytokines in acute renal failure.
AB  - A growing body of evidence indicates that inflammatory mechanisms contribute to
      toxin-induced acute renal failure as well as ischemia/reperfusion injury. A role
      for tumor necrosis factor-alpha (TNF-alpha) in mediating the inflammatory injury
      in cisplatin-induced acute renal failure has recently been established. Cisplatin
      induces the expression of TNF-alpha and TNF receptor subtype 2 (TNFR2) within the
      kidney. Genetic deletion of either TNF-alpha or TNFR2 substantially reduces
      cisplatin-induced renal failure and also necrosis and apoptosis within the
      kidney. Studies will be required to determine if pharmacologic inhibition of TNF
      alpha might reduce cisplatin-induced renal failure in humans.

PMID- 15461706
TI  - Acute renal failure: from renal physiology to the renal transcriptome.
AB  - Acute renal failure (ARF) is defined as an abrupt fall in glomerular filtration
      rate. Fully 5% of all patients admitted to the hospital undergo ARF with an
      attendant increase in morbidity and mortality. We have studied murine models of
      ischemia/reperfusion and cisplatin-induced renal failure in detail to determine
      the physiologic and molecular events that are responsible for the syndrome. Both
      forms of treatment induce necrosis of the proximal tubules, as well as more
      subtle changes in distal nephron viability, including apoptosis. Both forms are
      characterized by reduced renal blood, reduced glomerular filtration rate, and a
      urine-concentrating defect. Simultaneous with the onset of these morphologic and
      functional features is the commitment of cells to DNA synthesis and cell
      division, which is preceded by activation of signal transduction pathways and
      gene transcription that presumably underlie the morphologic and functional
      changes responsible for the syndrome. We describe a functional genomic approach
      using microarray data and available database searches to attempt to predict new
      targets for investigation of the pathogenesis and treatment of this disease.

PMID- 15461709
TI  - Anatomic and electrophysiological differences between chronic and paroxysmal
      forms of common atrial flutter and comparison with controls:.
AB  - Whether chronic typical atrial flutter differs from paroxysmal atrial flutter
      regarding electrophysiological properties of reentry pathways and cardiac
      function remains unknown. If so, can remodeling due to long duration of
      persistently rapid atrial or ventricular rates explain these changes? The aim of
      the study was to compare RA local conduction velocities and heart function
      parameters between three groups: (1) chronic atrial flutter, (2) paroxysmal
      atrial flutter, and (3) controls. The study evaluated 52 patients undergoing
      radiofrequency ablation for typical atrial flutter. There were 35 patients with
      chronic atrial flutter (62.7 +/- 14 years) and 17 patients with paroxysmal atrial
      flutter (62.7 +/- 10 years). Underlying structural heart disease was present in
      20 (57%) of 35 chronic atrial flutter patients and in 7 (41%) of 17 paroxysmal
      atrial flutter patients (P = 0.1). Chronic atrial flutter duration was 10.9 +/-
      17 months and paroxysmal atrial flutter duration was 8.5 +/- 10 (P = 0.06). RA
      conduction velocity measurements were carried out before ablation during sinus
      rhythm under pacing (600-ms cycle length) with a 12-pole steerable catheter
      positioned in the high lateral RA (poles 11-12 [H6]), mid-lateral RA (poles 9-10
      [H5]), and along the inferior vena caval tricuspid isthmus (poles 7-8 [H4]; 5-6
      [H3]; 3-4 [H2]) with its distal electrode pair at the coronary sinus origin (pole
      1-2 [H1]). Counter-clockwise RA conduction velocities were assessed from H6 to H1
      and clockwise RA conduction velocities from H1 to H6. After successful ablation,
      RA and LA areas, LV volumes, LVEF, inferior vena caval tricuspid annulus, and
      coronary sinus tricuspid annulus (septal isthmus) lengths were measured by two
      dimensional echocardiography. The control group included 12 patients without
      structural heart disease, referred for electrophysiological evaluation of AVN
      reentry. Counter-clockwise RA conduction velocities at the inferior vena caval
      tricuspid isthmus were lower in chronic atrial flutter than in paroxysmal atrial
      flutter (H4, 1.19 +/- 0.4 vs 1.89 +/- 1 m/s, P = 0.0051; H3, 1.14 +/- 0.4 vs 1.6
      +/- 0.7 m/s, P = 0.0015; H2, 1.16 +/- 0.4 vs 1.53 +/- 0.5 m/s, P < 0.0056 and H1,
      1.2 +/- 0.4 vs 1.5 +/- 0.4 m/s, P = 0.03, respectively). Counter-clockwise RA
      conduction velocities were identical at the high and mid-lateral RA. Counter
      clockwise caval isthmus RA conduction velocities from H3 to H1 were significantly
      different between chronic atrial flutter and controls (H3, 1.14 +/- 0.4 vs 1.7 +/
      0.3 m/s, P = 0.0014; H2, 1.16 +/- 0.4 vs 1.83 +/- 0.4 m/s, P < 0.0001 and H1,
      1.2 +/- 0.4 vs 1.94 +/- 0.4 m/s, P < 0.0001, respectively). A difference was
      found regarding clockwise isthmus RA conduction velocities between the two groups
      of atrial flutter and controls but not between chronic atrial flutter and
      paroxysmal atrial flutter. Respectively, chronic atrial flutter had greater RA
      and LA areas (24.5 +/- 5 vs 13 +/- 2 cm2; P < 0.0001 and 23 +/- 5 vs 16 +/- 3
      cm2, P < 0.0001), LV end-systolic and end-diastolic volumes (50 +/- 25 vs 32 +/-
      13 cm3, P = 0.0084 and 112 +/- 40 vs 85 +/- 25 cm3, P = 0.01), septal isthmus
      length (21 +/- 3 vs 13 +/- 2 mm, P < 0.0001), and inferior vena caval tricuspid
      isthmus length (39 +/- 6 vs 23 +/- 5 mm; P < 0.0001). Chronic common atrial
      flutter is characterized by more prolonged counter-clockwise conduction times and
      larger anatomic conduction pathways than the paroxysmal form, the causal
      relationship between electrophysiological and anatomic characteristics remains to
      be demonstrated.

PMID- 15461710
TI  - Clinical significance of preserving spontaneous QRS wave in the therapy of DDD
      pacing for sick sinus syndrome.
AB  - The aim of this clinical crossover study was to elucidate the effects of
      atrioventricular (AV) synchronous pacing on cardiac function in patients with
      sick sinus syndrome (SSS). Thirty SSS patients, each with dual chamber pacemaker
      (DDD), were enrolled and divided into two groups based on echocardiographic
      findings. Group A (n = 16) had hypertensive heart disease (wall thickness 11
      approximately 12 mm) or mitral or aortic regurgitation (Grade I or II). Group B
      (n = 14) had no organic heart disease. Three successive 3-month pacing periods
      were tested. For the first 3 months, long AV delay that achieved > 80%
      ventricular sensing was chosen. For the next 3 months, AV delay was abbreviated
      to achieve > 80% ventricular pacing at an optimal AV interval. For the final 3
      months, the first setting was resumed. At the end of each period, M mode
      echocardiography, pulsed-Doppler study, and measurement of plasma brain
      natriuretic peptide (BNP) level were conducted. In both groups, echocardiographic
      parameters were not significantly changed during the evaluation. In group A,
      plasma BNP level was significantly higher at the end of the short AV delay period
      than at the long AV delay period (P = 0.009), while in group B it did not differ
      during each period. AV synchronous pacing (> 80% ventricular pacing) in the SSS
      patients with a DDD pacemaker implanted could increase the ventricular load, and
      it is better to preserve the spontaneous QRS with the DDD mode with prolonged AV
      delay in patients with mild hypertensive or valvular disease.

PMID- 15461711
TI  - Assessment of ventricular repolarization in a large group of children with early
      onset deafness.
AB  - This study examined the ECG traces of 397 deaf children (age 12.5 +/- 2.9 years,
      range 6-19 years), after exclusion of cases with Jervell and Lange-Nielsen
      syndrome (JLNS), and compared them to those of 361 normal hearing counterparts
      (age 12.5 +/- 2.7 years; range 7-18 years). An observer, who was unaware of the
      hearing status of the subjects, measured QT and QTc intervals and calculated
      dispersions of QT and QTc from standard 12-lead ECGs recorded at a speed of 25
      mm/s at rest. Although the mean QT was found to be longer in deaf children than
      that observed in the control group (P < 0.0001), the mean QTc was significantly
      shorter (P < 0.0001). The mean heart rate was significantly lower in deaf
      children. When QT and QTc data were recompared after the children were grouped
      according to the heart rate, the observed difference became less significant or
      disappeared. In conclusion, there are no major abnormalities for repolarization
      parameters in children with congenital sensorineural deafness, when compared to
      hearing counterparts, if heart rates are similar. Based on these results, routine
      ECG screening of deaf children for repolarization abnormalities may be
      unnecessary unless they have a history of syncope or positive family history of
      syncope and/or early sudden death.

PMID- 15461712
TI  - Far-field R wave oversensing in dual chamber pacemakers designed for atrial
      arrhythmia management: effect of pacing site and lead tip to ring distance.
AB  - INAMA, G., et al.: Far-Field R Wave Oversensing in Dual Chamber Pacemakers
      Designed for Atrial Arrhythmia Management: Effect of Pacing Site and Lead Tip to
      Ring Distance. The aim of the study was to determine the incidence and practical
      implications of far-field R wave oversensing (FFRWO) and its association with
      pacing site and lead tip to ring spacing (TTRS) in implantable devices designed
      to diagnose and treat atrial tachyarrhythmias and programmed with a fixed and
      short postventricular blanking period. The study included 395 patients who were
      implanted with a DDDRP pacemaker and prospectively followed. At implant and
      follow-up visits FFRWO was assessed by analyzing lead electrical measures and
      atrial tachyarrhythmic episodes collected in the device diagnostics. During a
      median follow-up of 12 months 11 (2.8%) of 395 patients showed a clinically
      significant FFRWO that induced inappropriate detection or pacemaker
      malfunctioning. The atrial pacing site of these 11 patients was right atrium
      appendage (RAA) for 3 patients, representing 1.1% of 254 RAA patients, coronary
      sinus ostium (CSO) for 7 patients, representing 7.4% of 94 CSO patients (P <
      0.005 vs RAA), and lateral wall (LW) for 1 (2.9%) of 34 LW patients. The minimal
      value of the FFRWO to P wave ratio, measured at implant, associated with a
      clinically significant FFRWO was 0.6; therefore, a value of 0.5 was used as a
      cutoff to identify patients at risk of undesirable device behavior induced by
      FFRWO: there were 11 (9.6%) of 114 of RAA patients with short (< or = 10 mm)
      TTRS, 22 (18.8%) of 117 of RAA patients with long (> or = 17 mm) TTRS (P < 0.05
      vs short TTRS), 21 (30.6%) of 64 of CSO patients short TTRS (P < 0.001 vs RAA
      patients with short TTRS) and 3 (30%) of 10 of CSO patients with long TTRS. The
      analysis showed that, despite the short postventricular blanking time, FFRWO
      inducing undesired functioning in AT500 pacemakers is infrequent (2.8% of
      patients). Compared to RAA, the CSO lead position was more frequently associated
      with FFRWO.TTRS < 10 mm was associated with lower risk of clinically significant
      FFRWO in RAA. (PACE 2004; 27:1221-1230).

PMID- 15461714
TI  - Prevalence and characteristics of idiopathic outflow tract tachycardia with QRS
      alteration following catheter ablation requiring additional radiofrequency
      ablation at a different point in the outflow tract.
AB  - Subtle variations in QRS morphology occurs during idiopathic outflow tract
      ventricular tachycardia (OTVT), but no studies have clarified the prevalence and
      characteristics of the OTVT with altered QRS morphology following radiofrequency
      catheter ablation (RFA), which then require an additional RF application at a
      different portion of the outflow tract to abolish OTVT. Of 202 patients with a
      monomorphic VT or premature ventricular contraction (PVC) originating from the
      outflow tract, 6 (3%) showed changes in QRS morphology in the OTVT following RFA,
      requiring an additional RF application to the outflow tract at a different
      portion. In all six patients, RFA was applied for the first or second OTVT to a
      right or left ventricular endocardial site, with the other site being the left
      sinus of Valsalva. In each patient, OTVT before or after the changes in QRS
      morphology had characteristic ECG findings originating from a particular portion
      of the outflow tract. Changes in QRS morphology consistently included an increase
      or decrease in R wave amplitude in all inferior leads. Detailed continuous
      observation of QRS morphology in OTVT, especially R wave amplitude in inferior
      leads, is important for identifying changes of QRS morphology during catheter
      ablation. Mapping and ablation at a different portion of the outflow tract is
      then needed for cure.

PMID- 15461713
TI  - Electrophysiological mechanisms and catheter ablation of complex atrial
      arrhythmias from crista terminalis:.
AB  - Paroxysmal atrial fibrillation (PAF) can be initiated by ectopic activation from
      the crista terminalis. The crista terminalis conduction gap is also a critical
      isthmus in atrial reentrant arrhythmias like upper and lower loop reentry. The
      aim of this study was to investigate the mechanism and results of catheter
      ablation for complex atrial arrhythmias originating from the crista terminalis
      using the noncontact mapping system (NCM). The study population consisted of six
      patients (5 men, 1 woman; 70 +/- 9 years) with drug refractory PAF and
      typical/atypical atrial flutter. NCM identified the earliest ectopic activation
      originating from the crista terminalis in these six patients. The reentry circuit
      of atypical atrial flutter propagated around the upper crista terminalis in five
      patients, and lower crista terminalis in one patient. The reentry circuit of
      atypical atrial flutter and the initial reentry circuit of AF conducted through
      the crista terminalis gap in all patients. Radiofrequency applications were
      delivered on the sites of ectopy, which initiated AF. Substrate modification was
      also performed over the crista terminalis gap (six patients) and cavotricuspid
      isthmus (three patients) responsible for the reentry. During a mean follow-up of
      9 +/- 5 months (range 5-18 months), five patients were free of AF without
      antiarrhythmic drugs, and one patient did not have AF or atrial flutter using
      propafenone. NCM demonstrated the mechanism of crista terminalis ectopy
      initiating AF and associated typical/atypical atrial flutter. Catheter ablation
      of crista terminalis ectopy and substrate for the reentry guided by NCM
      successfully eliminated these atrial arrhythmias.

PMID- 15461715
TI  - Electrophysiological characteristics of accessory pathways with prolonged
      retrograde conduction.
AB  - Electrophysiological characteristics of an accessory pathway (AP) with a long
      ventriculoatrial (VA) interval (arbitrarily defined as > or = 50 ms and absence
      of continuous electrical activity) and no retrograde decremental property are
      described in this study. Fifteen patients (group 1) were compared with 171
      patients with normal VA conduction (group 2). Mean VA conduction time was 77 +/-
      24 versus 34 +/- 12 ms in group 1 versus group 2, respectively. Group 1 patients
      were older (55 +/- 14 vs 40 +/- 14 years), the male to female ratio was higher
      (2.8 vs 1.6), and APs were more prevalent on the right (60%) but manifest APs
      were lower (20% vs 54%) compared to group 2 patients (P < 0.05 in all cases). QRS
      morphology during induced atrioventricular reciprocating tachycardia was
      identical in both groups but the tachycardia cycle length was longer in group 1
      (373 +/- 29 vs 344 +/- 50 ms, P < 0.05). Retrograde AP block cycle length and
      effective refractory period were greater in group 1 (362 +/- 59 vs 293 +/- 57 ms;
      330 +/- 58 vs 273 +/- 55 ms, both P < 0.05). Adenosine (up to 18 mg) and
      verapamil (5-10 mg) failed to block the VA conduction via AP during ventricular
      pacing. In group 1 the number of radiofrequency lesions for a successful ablation
      were significantly less (3 +/- 2 vs 6 +/- 5, P < 0.05). In conclusion, APs with a
      long VA interval and no decremental retrograde conduction have
      electrophysiological characteristics that are different from those with a short
      VA interval. Role of aging deserves further exploration.

PMID- 15461716
TI  - Electroconvulsive therapy in patients with cardiac pacemakers and implantable
      cardioverter defibrillators.
AB  - Electroconvulsive therapy (ECT) is used to treat major depressive illness,
      especially in elderly and medically frail patients. Not uncommonly, these
      patients have cardiac pacemakers or implantable cardioverter defibrillators
      (ICDs). Only a few case reports in the literature describe the use of ECT in such
      patients. Herein we review our ECT experience treating 26 pacemaker patients and
      3 ICD patients. All patients obtained significant antidepressant benefits with
      ETC. Only one serious cardiac event occurred, a case of supraventricular
      tachycardia (SVT) requiring a stay on the cardiac intensive care unit. The SVT
      resolved and the patient went on to receive further uncomplicated ECT treatments.
      We conclude from this experience that with proper pre-ECT cardiac and
      pacemaker/defibrillator assessment, ECT can be safely and effectively
      administered to patients with an implanted cardiac device.

PMID- 15461717
TI  - Effects of transvenous pacing on cardiac troponin release.
AB  - Cardiac troponins are invaluable tools for the detection of minimal myocardial
      injury. No study to date has analyzed the effect of permanent cardiac pacing on
      minimal myocardial injury detection by cardiac troponin I (cTnI) measurement. We
      investigated 76 clinically stable patients (mean age 75 years, range 31-93 years,
      59% men) listed for elective endocardial permanent pacemaker insertion. Patients
      were required to have normal levels of cardiac cTnI, aspartate transaminase (AST)
      and creatinine kinase (CK) on a venous blood sample taken immediately prior to
      elective pacemaker implantation. Repeat measurements of AST, CK, and cTnI were
      performed at a mean of 19.2 post implantation. There was a detectable small rise
      in cTnI levels above normal in 21% of patients in a second blood sample taken 18
      21 hours later (mean cTnI 0.39 +/- 0.37 microg/L, normal < 0.15 microg/L). The
      only factor that correlated with this rise was prolonged x ray screening time for
      lead implantation.

PMID- 15461718
TI  - Relation between history of paroxysmal atrial fibrillation and
      electrophysiological abnormalities of atrial muscle.
AB  - Although electrophysiological abnormalities of atrial muscle have been evaluated
      in patients with paroxysmal atrial fibrillation (PAF), no prior study has
      determined the contribution of the patient's history of PAF to
      electrophysiological abnormalities. The study population consisted of 108
      patients (71 men; mean age, 57 +/- 14 years) with symptomatic and idiopathic PAF
      who underwent electrophysiological study. Before electrophysiological study,
      histories of frequency, number of PAF episodes per month, and duration, a time
      interval from the first episode of PAF to electrophysiological study, were
      examined. At electrophysiological study, endocardial electrograms from 12 right
      atrial sites were recorded during sinus rhythm, and the right atrial effective
      refractory period was determined. Longest duration of atrial electrograms,
      maximal number of fragmented deflections, and number of abnormal atrial
      electrograms recorded at the right atrial sites were significantly greater in the
      frequent group (> 1 PAF episode per month, n = 57) than in the infrequent group
      (< 1 PAF episode per month, n = 51) (98 +/- 18 ms vs 88 +/- 16 ms, P < 0.005; 8.7
      +/- 2.6 vs 7.5 +/- 2.6, P < 0.05; and 2.2 +/- 2.2 vs 1.4 +/- 1.6, P < 0.05,
      respectively). Indices of atrial vulnerability were also greater in the frequent
      group. Duration of PAF history was significantly correlated with longest duration
      r = 0.52, P < 0.0001), maximal number of fragmented deflections r = 0.51, P <
      0.0001), and number of abnormal atrial electrograms r = 0.58, P < 0.0001). More
      frequent episodes and longer history of PAF significantly increased the
      electrophysiological abnormalities of the atrial muscle, suggesting that PAF
      results in gradual electrical remodeling of the atrial muscle.

PMID- 15461719
TI  - Quantification of atrial tachyarrhythmia burden with an implantable pacemaker
      before and after pulmonary vein isolation.
AB  - Long-term efficacy of pulmonary vein (PV) ostial isolation for paroxysmal atrial
      fibrillation is difficult to assess. We evaluated the net duration of atrial
      tachyarrhythmia episodes (burden), atrial tachyarrhythmia episode frequency, and
      quality-of-life (QOL) before and after PV isolation in patients with an existing
      pacemaker featuring extensive diagnostic capabilities. Due to frequent
      recurrences of paroxysmal atrial fibrillation, PV isolation was performed 21 +/-
      10 months following pacemaker implantation on 12 patients (57 +/- 5 years) with
      normal left ventricular function. Atrial tachyarrhythmia burden (ATB) and episode
      frequency were monitored daily by the device both pre- and postablation. QOL
      questionnaires were collected at ablation and 1, 3, and 6 months thereafter.
      Patients were followed for 20 +/- 9 and 11 +/- 9 months pre- and postablation,
      respectively. Membrane-active antiarrhythmic medications were discontinued after
      ablation in 8 of 12 patients. PV isolation resulted in a significant reduction of
      ATB from a median of 3.2 hours/day (preablation) to 0.2 hours/day (postablation,
      P < 0.01, Wilcoxon signed-rank test). The median tachyarrhythmia frequency was
      6.4 episodes/day (preablation) and 0.3 episodes/day (postablation, P = 0.09). QOL
      measures significantly improved over the data collection intervals (P < 0.05).
      Tachyarrhythmia burden was positively associated with Symptom Checklist frequency
      and severity (P < 0.01). Significant long-term reductions in total ATB
      (symptomatic and asymptomatic) were observed. Furthermore, reductions in ATB were
      associated with improvements in QOL measures. Extensive monitoring capabilities
      in implantable devices help provide complete disclosure on the effect of PV
      isolation in paroxysmal atrial fibrillation patients.

PMID- 15461720
TI  - Assessment of regional wall motion by strain Doppler during biventricular pacing
      in patients with conventional indications for a pacemaker.
AB  - Biventricular pacing therapy is effective in patients with severe congestive
      heart failure. Strain Doppler imaging (SDI) is a new tool for measuring regional
      myocardial deformation. We evaluated regional wall motion by strain Doppler
      imaging in 13 patients who had conventional indications for a pacemaker (74 +/- 6
      years old) and in six with NYHA Class III or IV heart failure with a
      biventricular pacemaker (HF-RV: during right ventricular pacing, HF-BV: during
      biventricular pacing). The other seven patients had normal LV function (N-RV).
      Wall motion was assessed by strain of the myocardium, and the interval between
      the Q wave of the surface ECG and the peak strain (QPSI) was measured in three
      septal and three lateral segments. Interventricular contraction delay was
      determined as the interval between the onset of the left and right ventricular
      outflow waves. Intraventricular contraction delay was determined as the time
      difference between minimum and maximum QPSI. Strain of HF-RV was significantly
      greater than that of N-RV (-9.6%+/- 2.5% vs -14.4%+/- 2.3%, P < 0.0001).
      Intraventricular contraction delay of HF-RV was significantly greater than that
      of N-RV (273 +/- 12 vs 151 +/- 69 ms, P = 0.0004). Strain of HF-RV was not
      significantly greater than that of HF-BV (-9.6% +/- 2.5% vs -10.6% +/- 2.9%).
      Interventricular contraction delay of HF-RV was greater than that of HF-BV (37.2
      +/- 44.7 vs 16.2 +/- 47.4 ms, P < 0.0001). Intraventricular contraction delay of
      HF-RV was significantly greater than that of HF-BV (322 +/- 101 vs 209 +/- 88 ms,
      P = 0.0006). In conclusion, biventricular pacing improves both interventricular
      contraction delay and intraventricular contraction delay in patients with
      conventional indications for a pacemaker with severe congestive heart failure,
      and SDI is useful to predict the efficacy of biventricular pacing.

PMID- 15461721
TI  - Antitachycardia pacing for ventricular tachycardia using implantable cardioverter
      defibrillators:.

PMID- 15461722
TI  - Heart failure and pulmonary embolism:.

PMID- 15461723
TI  - On being a patient.

PMID- 15461724
TI  - Brugada electrocardiographic pattern elicited by inadvertent flecainide overdose.
AB  - In a 70-year-old man, without clinical suggestion of the hereditary form of the
      Brugada syndrome, severe flecainide overdose resulted in profound widening of the
      QRS complex and the development of ST-T abnormalities typical of the Brugada
      sign. Serial ECGs recorded over a 5-day period revealed a parallel pattern of
      dynamic intraventricular conduction defect and ST-segment elevation. Resolution
      of ST-segment elevation lagged behind resolution of the QRS widening by 16-20
      hours. Despite the marked Brugada abnormality no arrhythmia occurred and the
      patient recovered without complications.

PMID- 15461725
TI  - Resumption of atrioventricular conduction by levosimendan after radiofrequency
      ablation of the AV node:.
AB  - We report the case of a patient in whom radiofrequency catheter ablation of the
      AV node was initially successfully performed for persistent atrial fibrillation
      with fast ventricular rate, but in whom atrioventricular conduction transiently
      resumes following therapy with levosimendan. Plausible hypothesis are discussed
      as well as potential implications.

PMID- 15461726
TI  - Inappropriate implantable cardioverter defibrillator discharge following
      consumption of a dietary weight loss supplement.
AB  - This report describes the clinical course of a 40-year-old female who experienced
      repetitive ICD firing after consuming Metabolife 356, a multicomponent dietary
      weight loss supplement. Following the initiation of Metabolife 356, the patient
      experienced four shocks over a 3 day period with two 30 J shocks being delivered
      sequentially. Interrogation of the device revealed atrial tachycardia with 1:1 AV
      conduction at a rate of 240 beats/min. Metabolife 356 was discontinued and the
      dosage of sotalol was increased to 120 mg twice daily without recurrence of ICD
      discharge.

PMID- 15461727
TI  - Total failure to sense ventricular fibrillation with inappropriate defibrillator
      sensitivity adjustment.
AB  - Automatic Sensitivity Control, unique to St. Jude defibrillators, allows for
      programmable sensitivity threshold and refractory periods. However, inappropriate
      programming can lead to marked undersensing and potentially lethal complications.
      We report a case of complete failure to sense ventricular fibrillation with
      inappropriate sensitivity adjustments. Detailed review of the parameters with
      induction of ventricular fibrillation must be performed to assure adequate
      safety.

PMID- 15461728
TI  - Recurrent syncope triggered by inappropriate sinus tachycardia.
AB  - A 25-year-old woman with daily episodes of syncope and several related traumatic
      injuries was referred for electrophysiological study. Structural heart disease
      was excluded. Electrophysiological study revealed inappropriate sinus tachycardia
      with heart rates up to 190 beats/min. A sinus node modulation was performed.
      However, 5 days later the patient again developed syncope during sinus
      tachycardia at rates of 140 beats/min with systolic blood pressure of 60 mmHg.
      The patient subsequently underwent AVN ablation and implantation of a dual
      chamber pacemaker. The patient has remained asymptomatic during a 12-month follow
      up. This article reports on the first case of a moderate sinus tachycardia in a
      structurally normal heart as an underlying mechanism of recurrent episodes of
      syncope. While moderate supraventricular tachycardia in a structurally normal
      heart alone is unlikely to explain the severe symptoms, additional sympathovagal
      or humoral mechanisms induced by sinus tachycardia may contribute to syncopal
      events in this patient.

PMID- 15461729
TI  - Transvenous biventricular defibrillation can improve defibrillation threshold.
AB  - A case report of a patient with a high defibrillation threshold at initial
      implantation that was improved by the insertion of a shocking coil in the left
      lateral cardiac vein is discussed.

PMID- 15461730
TI  - Interference between pacemaker and video capsule endoscopy.
AB  - The wireless capsule video endoscopy is useful in patients with occult blood
      loss, but is contraindicated in patients with cardiac pacemaker (PM). No case of
      interference has been published. We report the case of a patient with a PM
      implanted in the abdominal wall. After capsule ingestion, cardiac monitoring
      showed no modification of the PM compartment (VOO, unipolar mode) but the capsule
      recording reveal more than 3 hours of loss of image. The wireless capsule
      endoscopy is safe in patients with PMs in VOO mode. Nevertheless important
      interference was noted in the recording when the capsule was near the PM.

PMID- 15461731
TI  - Thebesian valve imaging with electron beam CT angiography: implications for
      resynchronization therapy.
AB  - We report visualization of a prominent coronary sinus os valve (Thebesian valve),
      by electron beam computed tomographic angiography, which impeded an endocardial
      approach to left ventricular pacing. Resynchronization therapy was therefore
      performed with an epicardial approach to left ventricular lead placement.
      Electron beam computed tomographic angiography can provide detailed information
      for coronary sinus instrumentation, including anomalies potentially affecting the
      approach to resynchronization therapy.

PMID- 15461733
TI  - Heart rate variability and diastolic heart failure.

PMID- 15461735
TI  - Antioxidant therapy in uremia: evidence-based medicine?
AB  - Because of correlations between cardiovascular disease, inflammation, and renal
      failure, many investigators are pursuing nontraditional risk factors and
      therapies in order to reduce cardiovascular morbidity and mortality in the end
      stage renal disease (ESRD) population. Despite the disappointing lack of clinical
      effects with antioxidative therapies seen in large studies of the general
      population, some studies suggest a diminished cardiovascular risk in individuals
      with renal failure. This expanding new line of evidence is promising as a method
      to help alleviate the more than 20-fold increase in risk of cardiovascular events
      in the ESRD population. Most of the current available studies have evaluated
      laboratory or physiologic endpoints, such as endothelial function and measures of
      oxidative burden, and have evaluated relatively small numbers of patients.
      However, it is currently premature to initiate widespread clinical therapy with
      antioxidants. Further investigation in this area should be supported to see if
      reported benefits can be duplicated in more widespread study populations, and to
      more accurately define the most appropriate choice of therapy, mode of therapy,
      and dose.

PMID- 15461736
TI  - Hemodialysis-induced hypotension: impact of technologic advances.
AB  - Hemodialysis-induced hypotension is one of the most serious complications in
      renal replacement therapy. The main cause of intradialytic hypotension is
      hypovolemia due to an imbalance between the amount of fluid removed and the
      refilling capacity of the intravascular compartment. Hypotension occurs when
      compensatory mechanisms for hypovolemia are overwhelmed by excessive fluid
      removal. As long as renal replacement therapy is limited to only a few hours per
      week, intradialytic hypotension will continue to be a relevant problem. Research
      has mainly focused on enlarging the compensatory capacity for ultrafiltration
      induced hypovolemia. This article critically discusses the technical approaches
      that have been introduced into therapy in recent years with the promise of
      reducing dialysis-induced hypotensive episodes.

PMID- 15461737
TI  - Serum ferritin in chronic kidney disease: reconsidering the upper limit for iron
      treatment.
AB  - Intravenous iron treatment in hemodialysis patients improves the response to
      recombinant human erythropoietin (rHuEPO) and facilitates achievement of targets
      for hemoglobin and hematocrit. Excessive treatment, however, could expose
      patients to risks related to iron overload and oxidative stress. Therefore
      international treatment guidelines generally recommend that intravenous iron be
      discontinued when serum ferritin is greater than 500-1000 ng/ml. In this article
      we explore the relevant issues that inform the decisions as to what levels of
      serum ferritin are used as the upper limit for treatment. We conclude that the
      current published literature is inadequate for developing evidence-based
      guidelines. Clinical judgment is critical to properly weigh the risks and
      benefits of intravenous iron treatment in the context of the individual patient.

PMID- 15461738
TI  - Inadequate treatment of cardiovascular disease and cardiovascular disease risk
      factors in dialysis patients: a commentary.
AB  - Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in
      patients with end-stage renal disease (ESRD). Despite its significant impact on
      health outcomes, which would imply a need for aggressive intervention, both CVD
      and CVD risk factors are inadequately treated in this patient population. The
      reasons for this inadequate treatment are unclear. This article reviews the
      contribution of traditional risk factors to the burden of CVD in ESRD patients,
      outlines the evidence regarding undertreatment of CVD and traditional CVD risk
      factors, and identifies potential factors that may be responsible for inadequate
      cardiovascular care in ESRD patients.

PMID- 15461740
TI  - K/DOQI guidelines for bone metabolism and disease in chronic kidney disease
      patients: some therapeutic implications.
AB  - The National Kidney Foundation (NKF) has recently published clinical practice
      guidelines for bone metabolism and disease in chronic kidney disease (CKD)
      patients (the Kidney Disease Outcomes Quality Initiative [K/DOQI]). Data from the
      literature show that the majority of dialysis patients treated with traditional
      calcium-containing phosphorus binders and vitamin D or vitamin D analogue
      preparations have serum parathyroid hormone (PTH), calcium, and phosphorus levels
      outside these strict K/DOQI target ranges. In fact, it appears that achieving and
      maintaining the targets values set by these guidelines is virtually impossible
      without the simultaneous use of the new calcimimetic agents and non-calcium
      containing binders, agents that have significant cost barriers to their use in
      many patients. These guidelines are welcome, but they may be impractical for the
      majority of dialysis patients. The impact of these guidelines in improving the
      parameters of bone metabolism and disease among dialysis patients remains to be
      determined.

PMID- 15461745
TI  - Use of insulin and oral hypoglycemic medications in patients with diabetes
      mellitus and advanced kidney disease.
AB  - Diabetes mellitus is recognized as a leading cause of chronic kidney disease
      (CKD) and end-stage renal disease (ESRD) in the United States. There is a vast
      array of medications used to treat diabetes, including insulin and the
      sulfonylureas, as well as newer classes of drugs such as the thiazolidinediones
      and biguanides. In patients with reduced glomerular filtration rate (GFR), it is
      necessary to decrease the dosage of some of these drugs, while others are best
      avoided altogether. Accumulation of either the parent compound or its metabolites
      can result in symptomatic hypoglycemia, or in the case of metformin, significant
      lactic acidosis. In this article we will review the use of insulin and the
      various classes of oral medications used to treat type 2 diabetes mellitus,
      focusing on their pharmacokinetic properties and dosing in patients with advanced
      kidney disease.

PMID- 15461741
TI  - What unique acid-base considerations exist in dialysis patients?

PMID- 15461746
TI  - Metabolic acidosis and malnutrition in dialysis patients.
AB  - Acidosis is a classic uremic toxin that causes protein catabolism, mainly by
      selective breakdown of skeletal muscle protein. However, the importance of
      acidosis is often overlooked in dialysis patients. In the presence of acidosis,
      there is activation of the ubiquitin-proteasome machinery as well as the branched
      chain keto acid dehydrogenase, resulting in catabolism of muscle protein.
      Acidosis acts synergistically with other catabolic factors, such as inflammatory
      cytokines and insulin resistance, in inducing protein catabolism. There is ample
      laboratory evidence showing that correction of acidosis prevents the up
      regulation of the ubiquitin-proteasome machinery and reduces protein degradation.
      Randomized control trials further show that acidosis in dialysis patients can be
      treated successfully by a higher dialysate bicarbonate or lactate concentration,
      or by oral bicarbonate supplement. Correction of mild acidosis in dialysis
      patients is effective in improving nutritional status and reducing the duration
      of hospitalization.

PMID- 15461747
TI  - Measuring quality of dying in end-stage renal disease.
AB  - Palliative medicine operates under the presumption that it is possible to improve
      the quality of a patient's death. Nephrology has justifiably taken pride in its
      reliance on internal benchmarking and the use of quality targets to shape
      clinical practice innovations, and this article discusses the efforts that are
      being made to measure end-of-life care of dialysis patients. A tool called the
      Dialysis Quality of Dying Apgar is described that examines five domains (pain,
      nonpain symptoms, advance care planning, peacefulness, and time) which are scored
      and then summed. A recent interdisciplinary workgroup of renal professionals has
      commissioned a series of focus groups that have attempted to ascertain patient
      and family values and preferences for the management of terminal situations. The
      results are summarized, and they should hopefully form a basis for the
      development of additional research and clinical measurement tools.

PMID- 15461748
TI  - Improving outcomes in CKD and ESRD patients: carrying the torch from training to
      practice.
AB  - Practicing nephrologists are spending more time caring for end-stage renal
      disease (ESRD) and chronic kidney disease (CKD) patients. Despite this focus, and
      considerable advances in the understanding of those aspects of care that impact
      on clinical outcomes, morbidity, mortality, and quality of life for these
      patients has not improved substantially over the past decade. One of the possible
      explanations for this lack of progress is the structure of current nephrology
      training programs, where ESRD and CKD patient care is not emphasized. To address
      this issue, we developed a short preceptorship for second-year nephrology
      fellows, including didactic lectures and workshops. Of 67 participating fellows,
      50% were from programs offering 3 or fewer months of exposure to outpatient
      hemodialysis, and 25% reported no exposure to peritoneal dialysis. Of more
      concern, 25% reported no "official rounds" with an attending nephrologist on
      dialysis patients. If nephrologists are to take their appropriate place as
      leaders of the care delivery team, nephrology fellowships must be restructured
      with appropriate emphasis placed on the comprehensive care of ESRD and CKD
      patients.

PMID- 15461749
TI  - Peritoneal dialysis access-related procedures by nephrologists.
AB  - Traditionally the placement of a peritoneal dialysis (PD) catheter in a patient
      with end-stage renal disease (ESRD) has been accomplished by a surgeon and using
      general anesthesia. This approach often introduces delays in starting PD, incurs
      additional costs in utilizing an operating room as well as anesthesia services,
      and introduces the mortality risk associated with general anesthesia. Recent data
      have emphasized that interventional nephrologists can safely and successfully
      perform PD access procedures. In this context, operating room facilities and
      staff and anesthesia services are not required and catheter insertion can be
      performed in a procedure room using local anesthesia, thereby reducing costs and
      completely bypassing the mortality risk associated with general anesthesia. When
      performed by a nephrologist, the catheter insertion can be accomplished swiftly
      and dialysis therapy initiated in a timely manner. Once begun, the success of PD
      hinges on reliable and long-term access to the peritoneal cavity. Prospective
      randomized and nonrandomized studies have shown that PD catheters
      peritoneoscopically placed by nephrologists have fewer complications (infection,
      exit site leak) and longer catheter survival rates than those inserted
      surgically. Although PD offers a variety of advantages, it remains an
      underutilized form of renal replacement therapy. To counteract PD
      underutilization, at least two separate centers have demonstrated a positive
      impact on the growth of the PD population when catheter insertion is performed by
      nephrologists. This article presents PD access-related procedures currently
      performed by interventional nephrologists. Furthermore, some of the complicating
      issues (bowel perforation, catheter migration, prior abdominal surgery) related
      to PD catheter insertion and management are also discussed.

PMID- 15461750
TI  - Percutaneous technique of presternal peritoneal dialysis catheter placement.
AB  - Presternally exiting peritoneal dialysis (PD) catheters have been described as
      advantageous compared to abdominally exiting catheters with regard to infection,
      wound healing, and other complications. Placement of such catheters has only been
      described with open surgical techniques and not by percutaneous means. In this
      article we describe 15 patients who received percutaneously placed PD catheters
      with a presternal exit site. These patients received their procedures in an
      outpatient procedure room performed by an interventional nephrologist. In all but
      one case, immediate technical success was achieved. In only one case was
      peritonitis documented. All catheters are still functional, including some with
      follow-up as long as 15 months. Percutaneous placement of presternally exiting PD
      catheters is technically straightforward and can avoid an open surgical
      procedure.

PMID- 15461751
TI  - Use of low molecular weight heparins and glycoprotein IIb/IIIa inhibitors in
      patients with chronic kidney disease.
AB  - Despite aggressive intervention, cardiac causes of death, including acute
      coronary syndrome (ACS), continue to be a major source of mortality in patients
      with chronic kidney disease (CKD), including end-stage renal disease (ESRD).
      Multiple large prospective trials have demonstrated the clinical benefits of both
      low molecular weight heparin (LMWH) and glycoprotein (Gp) IIb/IIIa inhibitors in
      treating patients with ACS. Unfortunately patients with significant impairment of
      kidney function have generally been excluded from these major clinical trials.
      Consequently relatively little is known about the pharmacokinetics, appropriate
      dosing, efficacy, and safety of these medications in patients with CKD of various
      stages. This article examines the available literature regarding the
      pharmacokinetics, dosing, efficacy, and safety of LMWH and Gp IIb/IIIa inhibitors
      in patients with CKD.

PMID- 15461752
TI  - Shortness of breath and abdominal pain within minutes of starting hemodialysis.
AB  - A 45-year-old woman on hemodialysis without significant problems for 6 years
      developed acute onset of anxiety, shortness of breath, and abdominal pain within
      minutes of initiating her hemodialysis treatment. Her blood pressure was stable
      throughout the episode. The treatment was discontinued and she was admitted to
      the hospital. Routine blood chemistries were unremarkable except for mild
      eosinophilia (5%). An ethylene oxide reaction was suspected. She was dialyzed the
      following day after rinsing the dialyzer with 2 L of saline. A similar reaction
      occurred. The following day she was dialyzed on an ethylene oxide-free dialyzer
      and the hemodialysis treatment was uneventful.

PMID- 15461755
TI  - The spectrum of cutaneous lymphomas in patients less than 20 years of age.
AB  - Cutaneous lymphomas are rare in young patients and are mostly represented by
      mycosis fungoides and its variants and CD30+ lymphoproliferative disorders
      (lymphomatoid papulosis [LYP] and anaplastic large T-cell lymphoma). We report
      our observations in a series of 69 patients less than 20 years of age who
      presented either with primary cutaneous lymphoma (n = 62) or with secondary
      manifestations of extracutaneous disease (n = 7). Clinicopathologic features
      permitted classification of the cases into the following diagnostic categories:
      mycosis fungoides (n = 24, all primary cutaneous), anaplastic large T-cell
      lymphoma (n = 13, all primary cutaneous), LYP (n = 11, all primary cutaneous),
      subcutaneous "panniculitis-like" T-cell lymphoma (n = 1, primary cutaneous),
      small-medium pleomorphic T-cell lymphoma (n = 2, all primary cutaneous), natural
      killer (NK)/T-cell lymphoma, nasal-type (n = 1, secondary cutaneous), follicle
      center cell lymphoma (n = 1, primary cutaneous), marginal zone B-cell lymphoma (n
      = 7, all primary cutaneous), B-lymphoblastic lymphomas (n = 6, 3 primary and 3
      secondary cutaneous), specific cutaneous manifestations of Hodgkin disease (n =
      1, secondary cutaneous), and acute myeloid leukemia (n = 2, both secondary
      cutaneous). Cutaneous lymphoma in children should be differentiated from benign
      skin disorders that may simulate them. In particular, mycosis fungoides and LYP
      in this age group may present with clinicopathologic features reminiscent of
      inflammatory disorders such as pityriasis alba, vitiligo, pityriasis rosea, and
      pityriasis lichenoides et varioliformis acuta. Even in secondary cutaneous
      lymphomas, skin manifestations may be the first sign of the systemic disease, and
      a diagnosis may be achieved on examination of histopathologic specimens of a
      cutaneous lesion. Our study illustrates the wide spectrum of cutaneous lymphomas
      and leukemias in patients less than 20 years of age and underlines the need for
      proper interpretation of these lesions by dermatologists and dermatopathologists.

PMID- 15461756
TI  - Eyelash length in children and adolescents with allergic diseases.
AB  - Long eyelashes may be congenital, acquired in association with certain systemic
      diseases, or drug induced. In the past, long eyelashes were considered an
      external sign found in children with allergic diseases. However, this claim has
      never been examined in a controlled study. We compared the eyelash lengths of
      allergic children and adolescents with perennial allergic rhinitis, with or
      without bronchial asthma and atopic dermatitis (n = 60) to those of age- and sex
      matched nonallergic controls (n = 80). The eyelashes of the allergic patients
      were found to be significantly longer than those of the controls: 9.43 +/- 1.39
      mm versus 8.45 +/- 1.30 mm (p < 0.001). Eyelash length did not differ between
      patients with allergic rhinitis only (n = 31; 9.65 +/- 1.43 mm) and patients with
      allergic rhinitis and other allergic diseases (n = 29; 9.19 +/- 1.31 mm) (p =
      0.196). These results indicate that children and adolescents with allergic
      diseases have longer eyelashes compared to nonatopic controls and that long
      eyelashes may be a part of the phenotype of the allergic patient.

PMID- 15461757
TI  - Lipodystrophia centrifugalis abdominalis in Korea.
AB  - Lipodystrophia centrifugalis abdominalis infantilis is a rare disorder described
      exclusively in Asians. Thirty Korean patients (4 women, 20 girls, and 6 boys)
      with a clinical and/or histopathologic diagnosis of this disorder were evaluated.
      The mean age of onset was 6.2 years. Infantile or congenital onset was seen in
      only three girls and two boys. In 50% of females, onset was after 5 years of age.
      All patients had involvement of the lower abdomen and groin both as the site of
      onset and as the main site. Histopathologic analysis showed loss of fat with or
      without an infiltrate of lymphocytes and histiocytes in the subcutis. Only one
      patient responded to treatment, an adult female who received photochemotherapy
      with softening of the lesions and symptomatic improvement. In previous reports,
      the age of onset of this disorder was at an age younger than 5 years but older
      than infants, making the term lipodystrophia centrifugalis abdominalis juvenilis
      more appropriate. In our series, 50% of females had onset after 5 years of age
      and 12.5% after 18 years of age. In one woman, the lesion that developed at 4
      years of age progressed until adulthood. Our study of affected Korean patients
      showed a fourfold female predilection and later onset in female patients.

PMID- 15461758
TI  - The diagnostic criteria of Gianotti-Crosti syndrome: are they applicable to
      children in India?
AB  - In order to evaluate the applicability of the diagnostic criteria to children
      with Gianotti-Crosti syndrome (GCS) in India we retrieved all clinical records of
      children with a definite diagnosis of this syndrome seen over 30 months in a
      private dermatology practice. The controls were children for whom Gianotti-Crosti
      had been suspected but the final diagnosis was not this syndrome, and children in
      whom it was not suspected but who were diagnosed with any of the differential
      diagnoses of the syndrome. We documented the presence or absence of the positive
      and negative clinical features for all patients and controls. The clinical
      records of 23 children with GCS and 74 controls were retrieved. The three
      positive clinical features--1) papules or papulovesicles 1-10 mm in diameter on
      at least three of the following four sites: cheeks, buttocks, extensor surfaces
      of the forearms, extensor surfaces of legs; 2) being symmetrical; 3) lasting for
      at least 10 days--were sensitive and positively correlated with GCS. Both
      negative clinical features--extensive truncal lesions and scaly lesions--are
      negatively correlated with this syndrome. All 23 children with GCS and none of
      the controls fulfilled the set of diagnostic criteria. We concluded that the
      Gianotti-Crosti diagnostic criteria are applicable to affected children in India.

PMID- 15461759
TI  - Infantile acute hemorrhagic edema and rotavirus infection.
AB  - Infantile acute hemorrhagic edema (AHE) is a benign condition characterized by a
      dramatic onset of inflammatory edema and ecchymotic purpura in a target or
      cockade pattern. It is considered an uncommon form of cutaneous vasculitis
      occurring in children younger than 2 years of age. The outbreak is frequently
      preceded by an immunization or various infections. We describe an 11-month-old
      girl with rosette-shaped purpuric plaques on the face and limbs, clinically
      consistent with a diagnosis of AHE of the skin, associated with fever and
      diarrhea. Laboratory investigations showed a rotavirus infection, which has not
      previously been reported in association with AHE of the skin. The disease had a
      benign course without relapses. Appropriate microbiologic investigations are
      advisable to confirm the possible etiologic role of rotavirus.

PMID- 15461760
TI  - Transient myeloproliferative disorder causing a vesiculopustular eruption in a
      phenotypically normal neonate.
AB  - We report an unusual congenital vesiculopustular eruption arising in a neonate as
      the result of the transient myeloproliferative disorder (TMD) associated with
      trisomy 21. In this instance, the neonate was phenotypically normal, making the
      diagnosis more elusive. Initially the lesions were clinically suspicious for
      herpetic infection. The clinical scenario quickly became highly suggestive of
      leukemia cutis, given the infant's extremely high white blood cell count. Further
      examination revealed trisomy 21 in the leukemic cells and disomy 21 in the buccal
      keratinocytes, and a diagnosis of self-resolving TMD was made. Biopsy specimens
      of the lesions showed a sparse, perivascular, atypical, mononuclear infiltrate.
      We suggest that examination for a TMD be undertaken in neonates with a
      vesiculopustular eruption and leukemic white blood cell counts.

PMID- 15461761
TI  - Hydroa vacciniforme with oral mucosal involvement.
AB  - We report the occurrence of oral ulcers in a 6-year-old girl with hydroa
      vacciniforme. This finding has not hitherto been reported in the literature.

PMID- 15461762
TI  - Unilesional (segmental) mycosis fungoides presenting in childhood.
AB  - Mycosis fungoides is rare in children, and a unilesional presentation is also
      rare. A 13-year-old Kuwaiti boy with unilesional mycosis fungoides is described.
      Clinically he had a single indurated large plaque on the left shoulder with
      histopathologic features typical of cutaneous T-cell lymphoma. The diagnosis was
      further supported by the presence of a T-cell clone discovered through molecular
      biology studies of paraffin-embedded material. No other lesions were detected.
      The lesion showed a favorable response to local radiotherapy.

PMID- 15461763
TI  - An infantile Cushing syndrome due to misuse of topical steroid.
AB  - Chronic low-dose exogenous steroid therapy in children can result in hypothalamic
      pituitary-adrenal axis dysfunction. However, the development of Cushing syndrome
      from topical steroid therapy is unusual. A 9-month-old girl with a diagnosis of
      Cushing syndrome caused by long-term topical clobetasol propionate application
      was evaluated. The patient was found to have severe adrenal suppression. Limiting
      the use of steroid-containing drugs, prescription of less potent agents,
      especially during infancy, and warning of parents about potential side effects
      are very important.

PMID- 15461764
TI  - Dermatitis herpetiformis presenting as chronic urticaria.
AB  - Childhood dermatitis herpetiformis (DH) is an immunobullous disease associated
      with gluten-sensitive enteropathy. This disease is rare in children and is
      typically characterized by intensely pruritic vesicles on the extensor surfaces.
      Definitive diagnosis of DH depends on the direct immunofluorescence finding of
      granular or fibrillar IgA deposits along the basement membrane zone of biopsied
      perilesional skin. We report an 11-year-old boy with an unusual presentation of
      DH characterized by a 7-month history of chronic urticaria-like skin lesions. He
      had evanescent, largely asymptomatic, urticarial wheals on his trunk, face, and
      extremities that were unresponsive to conventional therapy for urticaria. Skin
      biopsy specimen findings were consistent with DH and direct immunofluorescence of
      perilesional skin was diagnostic. The patient had no symptoms of gluten-sensitive
      enteropathy at the time of diagnosis, and his skin lesions rapidly cleared with
      dapsone therapy. This patient serves to highlight an unusual presentation of
      childhood DH and the need to consider this diagnosis when evaluating chronic
      urticarial lesions in children.

PMID- 15461765
TI  - Mutation in the ED1 gene, Ala349Thr, in a Korean patient with X-linked
      hypohidrotic ectodermal dysplasia developing de novo.
AB  - Hypohidrotic ectodermal dysplasia (HED) is a very rare disease characterized by
      the virtual absence of eccrine glands, dry skin, scanty hair, and dental
      abnormalities. It is transmitted by an X-linked recessive gene or rarely an
      autosomal recessive gene. Therefore it is only males who fully express the
      condition. It is caused by mutations within the ED1 gene, which encodes a
      protein, ectodysplasin-A (EDA). Typically there is frontal bossing, saddle nose,
      pointed chin, a prominent supraorbital ridge with periorbital hyperpigmentation,
      and absence of teeth. Those affected show great intolerance to heat. In the
      current absence of effective treatment for many hereditary skin diseases,
      comprehensive, accurate prenatal or postnatal genetic counseling can provide
      information to parents at risk of having affected children. We report HED in a 6
      year-old boy with an Ala349Thr (GCA --> ACA) missense mutation developed de novo.
      Both parents and a 16-week gestational age fetus were healthy. We thought direct
      sequencing analysis for the ED1 gene using peripheral blood or amniotic fluid was
      preferable for an accurate diagnosis of this disease, although there was some
      risk of not detecting the mutation. After the results of this study were
      communicated to the parents, the mother was freed of her guilty feelings of the
      past 6 years and has now delivered a healthy male infant.

PMID- 15461766
TI  - The harlequin color change and association with prostaglandin E1.
AB  - The harlequin color change is an unusual cutaneous phenomenon observed in newborn
      infants as transient, benign episodes of a sharply demarcated erythema on half of
      the infant, with simultaneous contralateral blanching. In this report, two
      newborns with congenital heart anomalies demonstrated the harlequin color change,
      one whose skin findings showed a course related to the dose of systemic
      prostaglandin E1, suggesting a possible association. The benign, self-limited
      nature of the color change mandates that prostaglandin E1 not be discontinued for
      this reason. The entity is likely more common than the paucity of reports in the
      world literature suggests, and all physicians should recognize its graphic
      appearance to avoid unnecessary exposure to agents in an effort to treat it.

PMID- 15461767
TI  - Concomitant vitiligo and psoriasis in a patient treated with interferon alfa-2a
      for chronic hepatitis B infection.
AB  - Well-known cutaneous side effects of interferon (IFN)-alfa therapy include dry
      skin, pruritus, hair loss, and psoriasis. Presumably because of its potent
      immunomodulatory activity, the use of IFN-alfa has also led to the development of
      autoimmune diseases in susceptible individuals. Vitiligo, an autoimmune cutaneous
      disease, has been reported to occur during IFN-alfa therapy. We report a 10-year
      old girl with chronic hepatitis B infection in whom IFN-alfa treatment induced de
      novo development of vitiligo and psoriasis. Neither skin condition improved after
      withdrawal of interferon treatment. Concomitant occurrence of vitiligo and
      psoriasis due to IFN-alfa has not been reported previously.

PMID- 15461768
TI  - A pruritic linear urticarial rash, fever, and systemic inflammatory disease in
      five adolescents: adult-onset still disease or systemic juvenile idiopathic
      arthritis sine arthritis?
AB  - The characteristic rash of systemic juvenile idiopathic arthritis is a transient
      erythematous eruption associated with a quotidian spiking fever. Usually
      asymptomatic, it can be pruritic, with dermatographism at sites of scratching or
      pressure. An illness similar to this entity in adults is designated adult-onset
      Still disease. The relationship between the pediatric and adult disease is
      uncertain and differences in case definition have evolved. Specifically, a
      sustained arthritis for at least 6 weeks is required for a diagnosis of systemic
      juvenile idiopathic arthritis, whereas transient arthritis and arthralgia are
      accepted criteria in adult-onset Still disease. We describe five patients less
      than 16 years of age who presented with an acute illness characterized by fever
      and a distinctive skin eruption. Intense pruritus and linear erythematous lesions
      flared with a spiking fever, usually in the late afternoon and evening.
      Periorbital edema/erythema and nonlinear urticarial lesions were also seen. Two
      children had splinter hemorrhages of the nail beds and one girl developed a
      fixed, scaling, pigmented, linear eruption. Severe malaise, myalgia, arthralgia,
      and leukocytosis were present in every patient. Other systemic manifestations
      included sore throat, transient arthritis, abdominal pain, lymphadenopathy,
      hepatomegaly, splenomegaly, hyperferritinemia, and hepatic dysfunction. No
      patient had a sustained arthritis. The course of the disease was variable. One
      patient, diagnosed with macrophage activation syndrome, recovered on oral
      naproxen. Two patients responded to systemic corticosteroid therapy. One girl
      developed status epilepticus and died from aspiration and asphyxia. A boy with
      severe hepatitis developed renal failure and thrombotic thrombocytopenic purpura
      and was treated with plasmapheresis, dialysis, and systemic corticosteroids; he
      had recurrent episodes of rash and fever into adult life. These children did not
      fulfill the case definition of systemic juvenile idiopathic arthritis because
      they lacked a persistent arthritis. Adolescent and adult patients with the same
      clinical and laboratory findings are described under the rubric of adult-onset
      Still disease. Recognition of the distinctive urticarial skin eruption and
      spiking fever is important in the diagnosis of a disease with severe morbidity
      and potentially life-threatening complications.

PMID- 15461769
TI  - Videomicroscopy of venular malformations (port-wine stain type): prediction of
      response to pulsed dye laser.
AB  - Videomicroscopy has been found to be useful in determining the depth of ectasia
      of vascular malformations. Different patterns that hypothetically could predict
      the response of a vascular malformation to pulsed dye laser have been described.
      Our purpose was to determine if the dermoscopy pattern was able to predict the
      response to pulsed dye laser therapy and if it was independent of other known
      clinical variables. Thirty-three consecutive children presenting for evaluation
      or treatment of vascular malformations underwent videomicroscopy previous to
      pulsed dye laser therapy. Sixty-nine representative areas were evaluated before
      and after laser therapy. Other clinical factors, including location of the
      malformation, the patient's age and sex, and previous therapy, were also included
      in the analysis. We found that the dermoscopy pattern was differently distributed
      depending on the anatomic area. A superficial pattern was not present in the
      centrofacial area. An undefined pattern was most often present when a previously
      treated area was imaged. A superficial pattern independently predicted a good
      response to laser. The location of the lesion was another independent factor
      influencing the outcome. A new pattern consisting of a pale circular area
      surrounding a central brownish dot is described as negatively influencing the
      response to laser therapy. We concluded that videomicroscopy is a good tool for
      assessing which vascular malformations can be adequately treated with laser
      therapy, although other anatomic factors can influence the response.
      Videomicroscopy is particularly helpful in deciding when to end the treatment
      because it objectively shows when no further response can be expected, and is
      helpful for demonstrating this to patients and their parents.

PMID- 15461770
TI  - Reversible neurotoxicity after an overdose of topical lindane in an infant.
AB  - Lindane (gamma benzene hexachloride) is a widely prescribed topical scabicide
      because of its efficacy and cost-effectiveness. Although toxicity from a single
      proper application of lindane is generally not observed, the hazards of repeated
      applications, industrial exposure, and accidental ingestion have been well
      documented. We herein describe an infant with reversible neurotoxicity following
      repeated applications of 1% lindane for the treatment of scabies. The role of
      factors predisposing to increased absorption and the recommendations to minimize
      potential neurotoxicity are emphasized.

PMID- 15461771
TI  - Extensive fixed drug eruption secondary to vancomycin.
AB  - Fixed drug eruption is an infrequent but well-known adverse event most commonly
      associated with antibiotics and nonsteroidal anti-inflammatory medications. We
      herein describe a second reported instance of vancomycin-induced fixed drug
      eruption involving an extensive area of the body surface.

PMID- 15461772
TI  - What syndrome is this? Olmsted syndrome.

PMID- 15461773
TI  - A painless palmar nodule.

PMID- 15461775
TI  - Woolly hair nevus.

PMID- 15461776
TI  - Use of duct tape occlusion in the treatment of recurrent molluscum contagiosum.

PMID- 15461777
TI  - Chronic bullous dermatosis of childhood in north India.

PMID- 15461778
TI  - Cutaneous pili migrans in a 3-year-old child.

PMID- 15461779
TI  - Bullous recurrent eruption of incontinentia pigmenti.

PMID- 15461780
TI  - Multiple pyogenic granuloma involving female genitalia: a rare entity?

PMID- 15461781
TI  - Eosinophilic pustular folliculitis in infancy in a Japanese neonate.

PMID- 15461782
TI  - RNA integrity as a quality indicator during the first steps of RNP purifications
      : a comparison of yeast lysis methods.
AB  - BACKGROUND: The completion of several genome-sequencing projects has increased
      our need to assign functions to newly identified genes. The presence of a
      specific protein domain has been used as the determinant for suggesting a
      function for these new genes. In the case of proteins that are predicted to
      interact with mRNA, most RNAs bound by these proteins are still unknown. In
      yeast, several protocols for the identification of protein-protein interactions
      in high-throughput analyses have been developed during the last years leading to
      an increased understanding of cellular proteomics. If any of these protocols or
      similar approaches shall be used for the identification of mRNA-protein
      complexes, the integrity of mRNA is a critical factor. RESULTS: We compared the
      effect of different lysis protocols on RNA integrity. We report dramatic
      differences in RNA stability depending on the method used for yeast cell lysis.
      Glass bead milling and French Press lead to degraded mRNAs even in the presence
      of RNase inhibitors. Thus, they are not suitable to purify intact mRNP complexes
      or to identify specific mRNAs bound to proteins. CONCLUSION: We suggest a novel
      protocol, grinding deep-frozen cells, for the preparation of protein extracts
      that contain intact RNAs, as lysis method for the purification of mRNA-protein
      complexes from yeast cells.

PMID- 15461783
TI  - On the emergence of multifocal cancers.
AB  - Several tumors can exist as multiple lesions within a tissue. The lesions may
      either arise independently, or they may be monoclonal. The importance of multiple
      lesions for tumor staging, progression, and treatment is subject to debate. Here
      we use mathematical models to analyze the emergence of multiple, clonally related
      lesions within a single tissue. We refer to them as multi-focal cancers. We find
      that multifocal cancers can arise through a dynamical interplay between tumor
      promoting and inhibiting factors. This requires that tumor promoters act locally,
      while tumor inhibitors act over a longer range. An example of such factors may be
      angiogenesis promoters and inhibitors. The model further suggests that multifocal
      cancers represent an intermediate stage in cancer progression as the tumor
      evolves away from inhibition and towards promotion. Different patterns of
      progression can be distinguished: (i) If tumor inhibition is strong, the initial
      growth occurs as a unifocal and self contained lesion; progression occurs through
      bifurcation of the lesion and this gives rise to multiple lesions. As the tumor
      continues to evolve and pushes the balance between inhibition and promotion
      further towards promotion, the multiple lesions eventually give rise to a single
      large mass which can invade the entire tissue. (ii) If tumor inhibition is weaker
      upon initiation, growth can occur as a single lesion without the occurrence of
      multiple lesions, until the entire tissue is invaded. The model suggests that the
      sum of the tumor sizes across all lesions is the best characteristic which
      correlates with the stage and metastatic potential of the tumor.

PMID- 15461784
TI  - A novel approach to treatment of hypertension in diabetic patients - a
      multicenter, double-blind, randomized study comparing the efficacy of combination
      therapy of Eprosartan versus Ramipril with low-dose Hydrochlorothiazide and
      Moxonidine on blood pressure levels in patients with hypertension and associated
      diabetes mellitus type 2 - rationale and design [ISRCTN55725285].
AB  - Hypertension and diabetes mellitus are closely interrelated and coexist in as
      many as two-thirds of patients with type 2 diabetes. The consequent risk of such
      an association is an accelerated development of atherosclerotic cardiovascular
      disease and nephropathy complications.In choosing an antihypertensive agent,
      effectiveness needs to be accompanied by favourable metabolic, cardioprotective,
      and nephroprotective properties. Given the multifactorial nature of hypertension,
      the approach that has gained widespread agreement is treatment with more than one
      agent. Agents with different mechanisms of action increase antihypertensive
      efficacy because of synergistic impacts on the cardiovascular system. Combination
      therapy allows the use of lower doses of each antihypertensive agent which
      accounts for the excellent tolerability of combination products.The aim of the
      present study is to quantify the efficacy of combination therapy of Eprosartan
      600 mg respectively Ramipril 5 mg with low-dose Hydrochlorothiazide and
      Moxonidine on blood pressure levels in patients with essential hypertension and
      associated diabetes mellitus type 2.The use of monotherapy (Eprosartan or
      Ramipril) followed by addition of low-dose Hydrochlorothiazide as second agent
      and of Moxonidine as a third agent will be individualized to the severity of
      hypertension in the particular patient and to his/her degree of response to
      current treatment.

PMID- 15461785
TI  - Surface structure, model and mechanism of an insect integument adapted to be
      damaged easily.
AB  - BACKGROUND: Several sawfly larvae of the Tenthredinidae (Hymenoptera) are called
      easy bleeders because their whole body integument, except the head capsule,
      disrupts very easily at a given spot, under a slight mechanical stress at this
      spot. The exuding haemolymph droplet acts as a feeding deterrent towards
      invertebrate predators. The present study aimed to describe the cuticle surface,
      to consider it from a mechanistic point of view, and to discuss potential
      consequences of the integument surface in the predator-prey relationships.
      RESULTS: The integument surface of sawfly larvae was investigated by light
      microscopy (LM) and scanning electron microscopy (SEM) which revealed that the
      cuticle of easy bleeders was densely covered by what we call "spider-like"
      microstructures. Such microstructures were not detected in non-easy bleeders. A
      model by finite elements of the cuticle layer was developed to get an insight
      into the potential function of the microstructures during easy bleeding. Cuticle
      parameters (i.e., size of the microstructures and thickness of the epi-versus
      procuticle) were measured on integument sections and used in the model. A shear
      force applied on the modelled cuticle surface led to higher stress values when
      microstructures were present, as compared to a plan surface. Furthermore, by
      measuring the diameter of a water droplet deposited on sawfly larvae, the
      integument of several sawfly species was determined as hydrophobic (e.g., more
      than Teflon(R)), which was related to the sawfly larvae's ability to bleed
      easily. CONCLUSION: Easy bleeders show spider-like microstructures on their
      cuticle surface. It is suggested that these microstructures may facilitate
      integument disruption as well as render the integument hydrophobic. This latter
      property would allow the exuding haemolymph to be maintained as a droplet at the
      integument surface.

PMID- 15461786
TI  - Mapping medical careers: questionnaire assessment of career preferences in
      medical school applicants and final-year students.
AB  - BACKGROUND: The medical specialities chosen by doctors for their careers play an
      important part in the workforce planning of health-care services. However, there
      is little theoretical understanding of how different medical specialities are
      perceived or how choices are made, despite there being much work in general on
      this topic in occupational psychology, which is influenced by Holland's RIASEC
      (Realistic-Investigative-Artistic-Social-Enterprising-Conventional) typology of
      careers, and Gottfredson's model of circumscription and compromise. In this
      study, we use three large-scale cohorts of medical students to produce maps of
      medical careers. METHODS: Information on between 24 and 28 specialities was
      collected in three UK cohorts of medical students (1981, 1986 and 1991 entry), in
      applicants (1981 and 1986 cohorts, N = 1135 and 2032) or entrants (1991 cohort, N
      = 2973) and in final-year students (N = 330, 376, and 1437). Mapping used
      Individual Differences Scaling (INDSCAL) on sub-groups broken down by age and
      sex. The method was validated in a population sample using a full range of
      careers, and demonstrating that the RIASEC structure could be extracted. RESULTS:
      Medical specialities in each cohort, at application and in the final-year, were
      well represented by a two-dimensional space. The representations showed a close
      similarity to Holland's RIASEC typology, with the main orthogonal dimensions
      appearing similar to Prediger's derived orthogonal dimensions of 'Things-People'
      and 'Data-Ideas'. CONCLUSIONS: There are close parallels between Holland's
      general typology of careers, and the structure we have found in medical careers.
      Medical specialities typical of Holland's six RIASEC categories are Surgery
      (Realistic), Hospital Medicine (Investigative), Psychiatry (Artistic), Public
      Health (Social), Administrative Medicine (Enterprising), and Laboratory Medicine
      (Conventional). The homology between medical careers and RIASEC may mean that the
      map can be used as the basis for understanding career choice, and for providing
      career counselling.

PMID- 15461787
TI  - ImageParser: a tool for finite element generation from three-dimensional medical
      images.
AB  - BACKGROUND: The finite element method (FEM) is a powerful mathematical tool to
      simulate and visualize the mechanical deformation of tissues and organs during
      medical examinations or interventions. It is yet a challenge to build up an FEM
      mesh directly from a volumetric image partially because the regions (or
      structures) of interest (ROIs) may be irregular and fuzzy. METHODS: A software
      package, ImageParser, is developed to generate an FEM mesh from 3-D tomographic
      medical images. This software uses a semi-automatic method to detect ROIs from
      the context of image including neighboring tissues and organs, completes
      segmentation of different tissues, and meshes the organ into elements. RESULTS:
      The ImageParser is shown to build up an FEM model for simulating the mechanical
      responses of the breast based on 3-D CT images. The breast is compressed by two
      plate paddles under an overall displacement as large as 20% of the initial
      distance between the paddles. The strain and tangential Young's modulus
      distributions are specified for the biomechanical analysis of breast tissues.
      CONCLUSION: The ImageParser can successfully exact the geometry of ROIs from a
      complex medical image and generate the FEM mesh with customer-defined
      segmentation information.

PMID- 15461788
TI  - Role of primary surgery in advanced ovarian cancer.
AB  - BACKGROUND: Major issues in surgery for advanced ovarian cancer remain
      unresolved. Existing treatment guidelines are supported by a few published
      reports and fewer prospective randomized clinical trials. METHODS: We reviewed
      published reports on primary surgical treatment, surgical expertise, inadequate
      primary surgery/quality assurance, neoadjuvant chemotherapy, interval debulking,
      and surgical prognostic factors in advanced ovarian cancer to help resolve
      outstanding issues. RESULTS: The aim of primary surgery is a well-planned and
      complete intervention with optimal staging and surgery. Surgical debulking is
      worthwhile as there are further effective treatments available to control
      unresectable residual disease. Patients of gynecologic oncology specialist
      surgeons have better survival rates. This may reflect a working 'culture' rather
      than better technical skills. One major problem though, is that despite pleas to
      restrict surgery to experienced surgeons, specialist centers are often left to
      cope with the results of inadequate primary surgical resections. Patients with
      primary chemotherapy or those who have had suboptimal debulking may benefit from
      interval debulking. A proposal for a better classification of residual tumor is
      given. CONCLUSIONS: Optimal surgical interventions have definite role to play in
      advanced ovarian cancers. Improvements in surgical treatment in the general
      population will probably improve patients' survival when coupled with
      improvements in current chemotherapeutic approaches.

PMID- 15461789
TI  - ArrayD: a general purpose software for microarray design.
AB  - BACKGROUND: Microarray is a high-throughput technology to study expression of
      thousands of genes in parallel. A critical aspect of microarray production is the
      design aimed at space optimization while maximizing the number of gene probes and
      their replicates to be spotted. RESULTS: We have developed a software called
      'ArrayD' that offers various alternative design solutions for an array given a
      set of user requirements. The user feeds the following inputs: type of source
      plates to be used, number of gene probes to be printed, number of replicates and
      number of pins to be used for printing. The solutions are stored in a text file.
      The choice of a design solution to be used will be governed by the spotting
      chemistry to be used and the accuracy of the robot. CONCLUSIONS: ArrayD is a
      software for standard cartesian robots. The software aids users in preparing a
      judicious and elegant design. ArrayD is universally applicable and is available
      at http://www.igib.res.in/scientists/arrayd/arrayd.html.

PMID- 15461790
TI  - Extraabdominal fibromatosis in retroperitoneal space.
AB  - BACKGROUND: Fibromatosis or desmoid tumor covers a broad spectrum of benign
      fibrous tissue proliferations. It is characterized by infiltrative growth and a
      tendency towards recurrence; however, unlike sarcoma, it never metastasizes. CASE
      PRESENTATION: We report on a case of extraabdominal fibromatosis originating from
      the retroperitoneal space in a 43-year-old woman. Seven years earlier she had
      undergone ureterolysis and ureteroureterostomy for ureteral obstruction. Computed
      tomography revealed a tumor between the iliocostalis and the psoas muscle.
      Histopathological evaluation revealed uniform proliferation of spindle cells,
      with a moderate amount of collagen fibers, suggesting extraabdominal fibromatosis
      (desmoid tumor). The tumor was surgically resected, and since then, the patient
      has remained asymptomatic without any restrictions of daily living activities and
      without any signs of tumor recurrence during the two-year follow-up. CONCLUSIONS:
      Complete resection is the treatment of choice. Adjuvant therapy using non
      steroidal anti-inflammatory agents, tamoxifen, interferon, anti-neoplastic
      agents, and radiotherapy, either alone or in combination finds application for
      unresectable or recurrent cases.

PMID- 15461792
TI  - A comprehensive transcript index of the human genome generated using microarrays
      and computational approaches.
AB  - BACKGROUND: Computational and microarray-based experimental approaches were used
      to generate a comprehensive transcript index for the human genome.
      Oligonucleotide probes designed from approximately 50,000 known and predicted
      transcript sequences from the human genome were used to survey transcription from
      a diverse set of 60 tissues and cell lines using ink-jet microarrays. Further,
      expression activity over at least six conditions was more generally assessed
      using genomic tiling arrays consisting of probes tiled through a repeat-masked
      version of the genomic sequence making up chromosomes 20 and 22. RESULTS: The
      combination of microarray data with extensive genome annotations resulted in a
      set of 28,456 experimentally supported transcripts. This set of high-confidence
      transcripts represents the first experimentally driven annotation of the human
      genome. In addition, the results from genomic tiling suggest that a large amount
      of transcription exists outside of annotated regions of the genome and serves as
      an example of how this activity could be measured on a genome-wide scale.
      CONCLUSIONS: These data represent one of the most comprehensive assessments of
      transcriptional activity in the human genome and provide an atlas of human gene
      expression over a unique set of gene predictions. Before the annotation of the
      human genome is considered complete, however, the previously unannotated
      transcriptional activity throughout the genome must be fully characterized.

PMID- 15461793
TI  - Variation in alternative splicing across human tissues.
AB  - BACKGROUND: Alternative pre-mRNA splicing (AS) is widely used by higher
      eukaryotes to generate different protein isoforms in specific cell or tissue
      types. To compare AS events across human tissues, we analyzed the splicing
      patterns of genomically aligned expressed sequence tags (ESTs) derived from
      libraries of cDNAs from different tissues. RESULTS: Controlling for differences
      in EST coverage among tissues, we found that the brain and testis had the highest
      levels of exon skipping. The most pronounced differences between tissues were
      seen for the frequencies of alternative 3' splice site and alternative 5' splice
      site usage, which were about 50 to 100% higher in the liver than in any other
      human tissue studied. Quantifying differences in splice junction usage, the
      brain, pancreas, liver and the peripheral nervous system had the most distinctive
      patterns of AS. Analysis of available microarray expression data showed that the
      liver had the most divergent pattern of expression of serine-arginine protein and
      heterogeneous ribonucleoprotein genes compared to the other human tissues
      studied, possibly contributing to the unusually high frequency of alternative
      splice site usage seen in liver. Sequence motifs enriched in alternative exons in
      genes expressed in the brain, testis and liver suggest specific splicing factors
      that may be important in AS regulation in these tissues. CONCLUSIONS: This study
      distinguishes the human brain, testis and liver as having unusually high levels
      of AS, highlights differences in the types of AS occurring commonly in different
      tissues, and identifies candidate cis-regulatory elements and trans-acting
      factors likely to have important roles in tissue-specific AS in human cells.

PMID- 15461794
TI  - Alternative splicing of mouse transcription factors affects their DNA-binding
      domain architecture and is tissue specific.
AB  - BACKGROUND: Analyzing proteins in the context of all available genome and
      transcript sequence data has the potential to reveal functional properties not
      accessible through protein sequence analysis alone. To analyze the impact of
      alternative splicing on transcription factor (TF) protein structure, we
      constructed a comprehensive database of splice variants in the mouse
      transcriptome, called MouSDB3 containing 461 TF loci. RESULTS: Our analysis
      revealed that 62% of these loci in MouSDB3 have variant exons, compared to 29% of
      all loci. These variant TF loci contain a total of 324 alternative exons, of
      which 23% are in-frame. When excluded, 80% of in-frame alternative exons alter
      the domain architecture of the protein as computed by SMART (simple modular
      architecture research tool). Sixty-eight % of these exons directly affect the
      coding regions of domains important for TF function. Seventy-five % of the
      domains affected are DNA-binding domains. Tissue distribution analyses of variant
      mouse TFs reveal that they have more alternatively spliced forms in 14 of the 18
      tissues analyzed when compared to all the loci in MouSDB3. Further, TF isoforms
      are homogenous within a given single tissue and are heterogeneous across
      different tissues, indicating their tissue specificity. CONCLUSIONS: Our study
      provides quantitative evidence that alternative splicing preferentially adds or
      deletes domains important to the DNA-binding function of the TFs. Analyses
      described here reveal the presence of tissue-specific alternative splicing
      throughout the mouse transcriptome. Our findings provide significant biological
      insights into control of transcription and regulation of tissue-specific gene
      expression by alternative splicing via creation of tissue-specific TF isoforms.

PMID- 15461795
TI  - A scale of functional divergence for yeast duplicated genes revealed from
      analysis of the protein-protein interaction network.
AB  - BACKGROUND: Studying the evolution of the function of duplicated genes usually
      implies an estimation of the extent of functional conservation/divergence between
      duplicates from comparison of actual sequences. This only reveals the possible
      molecular function of genes without taking into account their cellular
      function(s). We took into consideration this latter dimension of gene function to
      approach the functional evolution of duplicated genes by analyzing the protein
      protein interaction network in which their products are involved. For this, we
      derived a functional classification of the proteins using PRODISTIN, a
      bioinformatics method allowing comparison of protein function. Our work focused
      on the duplicated yeast genes, remnants of an ancient whole-genome duplication.
      RESULTS: Starting from 4,143 interactions, we analyzed 41 duplicated protein
      pairs with the PRODISTIN method. We showed that duplicated pairs behaved
      differently in the classification with respect to their interactors. The
      different observed behaviors allowed us to propose a functional scale of
      conservation/divergence for the duplicated genes, based on interaction data. By
      comparing our results to the functional information carried by GO annotations and
      sequence comparisons, we showed that the interaction network analysis reveals
      functional subtleties, which are not discernible by other means. Finally, we
      interpreted our results in terms of evolutionary scenarios. CONCLUSIONS: Our
      analysis might provide a new way to analyse the functional evolution of
      duplicated genes and constitutes the first attempt of protein function
      evolutionary comparisons based on protein-protein interactions.

PMID- 15461796
TI  - Genomic neighborhoods for Arabidopsis retrotransposons: a role for targeted
      integration in the distribution of the Metaviridae.
AB  - BACKGROUND: Retrotransposons are an abundant component of eukaryotic genomes. The
      high quality of the Arabidopsis thaliana genome sequence makes it possible to
      comprehensively characterize retroelement populations and explore factors that
      contribute to their genomic distribution. RESULTS: We identified the full
      complement of A. thaliana long terminal repeat (LTR) retroelements using
      RetroMap, a software tool that iteratively searches genome sequences for reverse
      transcriptases and then defines retroelement insertions. Relative ages of full
      length elements were estimated by assessing sequence divergence between LTRs: the
      Pseudoviridae were significantly younger than the Metaviridae. All retroelement
      insertions were mapped onto the genome sequence and their distribution was
      distinctly non-uniform. Although both Pseudoviridae and Metaviridae tend to
      cluster within pericentromeric heterochromatin, this association is significantly
      more pronounced for all three Metaviridae sublineages (Metavirus, Tat and
      Athila). Among these, Tat and Athila are strictly associated with pericentromeric
      heterochromatin. CONCLUSIONS: The non-uniform genomic distribution of the
      Pseudoviridae and the Metaviridae can be explained by a variety of factors
      including target-site bias, selection against integration into euchromatin and
      pericentromeric accumulation of elements as a result of suppression of
      recombination. However, comparisons based on the age of elements and their
      chromosomal location indicate that integration-site specificity is likely to be
      the primary factor determining distribution of the Athila and Tat sublineages of
      the Metaviridae. We predict that, like retroelements in yeast, the Athila and Tat
      elements target integration to pericentromeric regions by recognizing a specific
      feature of pericentromeric heterochromatin.

PMID- 15461797
TI  - Insertion bias and purifying selection of retrotransposons in the Arabidopsis
      thaliana genome.
AB  - BACKGROUND: Genome evolution and size variation in multicellular organisms are
      profoundly influenced by the activity of retrotransposons. In higher eukaryotes
      with compact genomes retrotransposons are found in lower copy numbers than in
      larger genomes, which could be due to either suppression of transposition or to
      elimination of insertions, and are non-randomly distributed along the
      chromosomes. The evolutionary mechanisms constraining retrotransposon copy number
      and chromosomal distribution are still poorly understood. RESULTS: I investigated
      the evolutionary dynamics of long terminal repeat (LTR)-retrotransposons in the
      compact Arabidopsis thaliana genome, using an automated method for obtaining
      genome-wide, age and physical distribution profiles for different groups of
      elements, and then comparing the distributions of young and old insertions.
      Elements of the Pseudoviridae family insert randomly along the chromosomes and
      have been recently active, but insertions tend to be lost from euchromatic
      regions where they are less likely to fix, with a half-life estimated at
      approximately 470,000 years. In contrast, members of the Metaviridae
      (particularly Athila) preferentially target heterochromatin, and were more active
      in the past. CONCLUSION: Diverse evolutionary mechanisms have constrained both
      the copy number and chromosomal distribution of retrotransposons within a single
      genome. In A. thaliana, their non-random genomic distribution is due to both
      selection against insertions in euchromatin and preferential targeting of
      heterochromatin. Constant turnover of euchromatic insertions and a decline in
      activity for the elements that target heterochromatin have both limited the
      contribution of retrotransposon DNA to genome size expansion in A. thaliana.

PMID- 15461798
TI  - Bioconductor: open software development for computational biology and
      bioinformatics.
AB  - The Bioconductor project is an initiative for the collaborative creation of
      extensible software for computational biology and bioinformatics. The goals of
      the project include: fostering collaborative development and widespread use of
      innovative software, reducing barriers to entry into interdisciplinary scientific
      research, and promoting the achievement of remote reproducibility of research
      results. We describe details of our aims and methods, identify current
      challenges, compare Bioconductor to other open bioinformatics projects, and
      provide working examples.

PMID- 15461799
TI  - Development of a method for screening short-lived proteins using green
      fluorescent protein.
AB  - We have developed a screening technology for the identification of short-lived
      proteins. A green fluorescent protein (GFP)-fusion cDNA library was generated for
      monitoring degradation kinetics. Cells expressing a subset of the GFP-cDNA
      expression library were screened to recover those in which the fluorescence
      signal diminished rapidly when protein synthesis was inhibited. Thirty clones
      that met the screening criteria were characterized individually. Twenty-three
      (73%) proved to have a half-life of 4 hours or less.

PMID- 15461800
TI  - Genome-wide mutagenesis of Zea mays L. using RescueMu transposons.
AB  - Derived from the maize Mu1 transposon, RescueMu provides strategies for maize
      gene discovery and mutant phenotypic analysis. 9.92 Mb of gene-enriched sequences
      next to RescueMu insertion sites were co-assembled with expressed sequence tags
      and analyzed. Multiple plasmid recoveries identified probable germinal insertions
      and screening of RescueMu plasmid libraries identified plants containing probable
      germinal insertions. Although frequently recovered parental insertions and
      insertion hotspots reduce the efficiency of gene discovery per plasmid, RescueMu
      targets a large variety of genes and produces knockout mutants.

PMID- 15461801
TI  - A reverse genetic screen in Drosophila using a deletion-inducing mutagen.
AB  - We report the use of the cross-linking drug hexamethylphosphoramide (HMPA), which
      introduces small deletions, as a mutagen suitable for reverse genetics in the
      model organism Drosophila melanogaster. A compatible mutation-detection method
      based on resolution of PCR fragment-length polymorphisms on standard DNA
      sequencers is implemented. As the spectrum of HMPA-induced mutations is similar
      in a variety of organisms, it should be possible to transfer this mutagenesis and
      detection procedure to other model systems.

PMID- 15461802
TI  - A genome annotation-driven approach to cloning the human ORFeome.
AB  - We have developed a systematic approach to generating cDNA clones containing full
      length open reading frames (ORFs), exploiting knowledge of gene structure from
      genomic sequence. Each ORF was amplified by PCR from a pool of primary cDNAs,
      cloned and confirmed by sequencing. We obtained clones representing 70% of genes
      on human chromosome 22, whereas searching available cDNA clone collections found
      at best 48% from a single collection and 60% for all collections combined.

PMID- 15461804
TI  - Twilight of a hero.
AB  - The hope for those afflicted with Parkinson's is embryonic stem cell therapy,
      which depends on research that the Bush administration is doing its best to
      strangle.

PMID- 15461803
TI  - Complete genome sequence of the industrial bacterium Bacillus licheniformis and
      comparisons with closely related Bacillus species.
AB  - BACKGROUND: Bacillus licheniformis is a Gram-positive, spore-forming soil
      bacterium that is used in the biotechnology industry to manufacture enzymes,
      antibiotics, biochemicals and consumer products. This species is closely related
      to the well studied model organism Bacillus subtilis, and produces an assortment
      of extracellular enzymes that may contribute to nutrient cycling in nature.
      RESULTS: We determined the complete nucleotide sequence of the B. licheniformis
      ATCC 14580 genome which comprises a circular chromosome of 4,222,336 base-pairs
      (bp) containing 4,208 predicted protein-coding genes with an average size of 873
      bp, seven rRNA operons, and 72 tRNA genes. The B. licheniformis chromosome
      contains large regions that are colinear with the genomes of B. subtilis and
      Bacillus halodurans, and approximately 80% of the predicted B. licheniformis
      coding sequences have B. subtilis orthologs. CONCLUSIONS: Despite the
      unmistakable organizational similarities between the B. licheniformis and B.
      subtilis genomes, there are notable differences in the numbers and locations of
      prophages, transposable elements and a number of extracellular enzymes and
      secondary metabolic pathway operons that distinguish these species. Differences
      include a region of more than 80 kilobases (kb) that comprises a cluster of
      polyketide synthase genes and a second operon of 38 kb encoding plipastatin
      synthase enzymes that are absent in the B. licheniformis genome. The availability
      of a completed genome sequence for B. licheniformis should facilitate the design
      and construction of improved industrial strains and allow for comparative
      genomics and evolutionary studies within this group of Bacillaceae.

PMID- 15461806
TI  - Hotspots of homologous recombination in the human genome: not all homologous
      sequences are equal.
AB  - Homologous recombination between alleles or non-allelic paralogous sequences does
      not occur uniformly but is concentrated in 'hotspots' with high recombination
      rates. Recent studies of these hotspots show that they do not share common
      sequence motifs, but they do have other features in common.

PMID- 15461805
TI  - Genomic and proteomic adaptations to growth at high temperature.
AB  - Most positively selected mutations cause changes in metabolism, resulting in a
      better-adapted phenotype. But as well as acting on the information content of
      genes, natural selection may also act directly on nucleic acid and protein
      molecules. We review the evidence for direct temperature-dependent natural
      selection acting on genomes, transcriptomes and proteomes.

PMID- 15461807
TI  - Global nucleosome distribution and the regulation of transcription in yeast.
AB  - Recent studies show that active regulatory regions of the yeast genome have a
      lower density of nucleosomes than other regions, and that there is an inverse
      correlation between nucleosome density and the transcription rate of a gene. This
      may be the result of transcription factors displacing nucleosomes.

PMID- 15461809
TI  - Can we find the genes involved in complex traits?

PMID- 15461808
TI  - Gene-dosage effects in Down syndrome and trisomic mouse models.
AB  - The abnormalities found in human Down syndrome (trisomy 21) have been thought to
      result from increased expression of genes on chromosome 21 because of their
      higher gene dosage. Now, several groups have shown this to be generally the case,
      but some inter-individual variability and other exceptions were found.

PMID- 15461810
TI  - New pulses in plant research.

PMID- 15461811
TI  - The lords of the genomes.

PMID- 15461812
TI  - Apolipoprotein M.
AB  - Apolipoprotein M (apoM) is a 26-kDa protein that is mainly associated with high
      density lipoprotein (HDL) in human plasma, with a small proportion present in
      triglyceride-rich lipoproteins (TGRLP) and low-density lipoproteins (LDL). Human
      apoM gene is located in p21.31 on chromosome 6 (chromosome 17, in mouse). Human
      apoM cDNA (734 base pairs) encodes 188-amino acid residue-long protein. It
      belongs to lipocalin protein superfamily. Human tissue expression array study
      indicates that apoM is only expressed in liver and in kidney and small amounts
      are found in fetal liver and kidney. In situ apoM mRNA hybridization demonstrates
      that apoM is exclusively expressed in the hepatocytes and in the tubule
      epithelial cells in kidney. Expression of apoM could be regulated by platelet
      activating factor (PAF), transforming growth factors (TGF), insulin-like growth
      factor (IGF) and leptin in vivo and/or in vitro. It has been demonstrated that
      apoM expression is dramatically decreased in apoA-I deficient mouse. Hepatocyte
      nuclear factor-1alpha (HNF-1alpha) is an activator of apoM gene promoter.
      Deficiency of HNF-1alpha mouse shows lack of apoM expression. Mutations in HNF
      1alpha (MODY3) have reduced serum apoM levels. Expression of apoM is
      significantly decreased in leptin deficient (ob/ob) mouse or leptin receptor
      deficient (db/db) mouse. ApoM concentration in plasma is positively correlated to
      leptin level in obese subjects. These may suggest that apoM is related to the
      initiation and progression of MODY3 and/or obesity.

PMID- 15461813
TI  - Idiopathic isolated clitoromegaly: A report of two cases.
AB  - BACKGROUND: Clitoromegaly is a frequent congenital malformation, but acquired
      clitoral enlargement is relatively rare. METHODS: Two acquired clitoromegaly
      cases treated in Ataturk Training Hospital, Izmir, Turkey are presented. RESULTS:
      History from both patients revealed clitoromegaly over the last three years.
      Neither gynecological nor systemic abnormalities were detected in either patient.
      Karyotype analyses and hormonal tests were normal. Abdominal and gynaecological
      ultrasound did not show any cystic lesion or other abnormal finding. Computerized
      tomography scan of the adrenal glands was normal. Clitoroplasty with preservation
      of neurovascular pedicles was performed for the treatment of clitoromegaly.
      CONCLUSION: The patients were diagnosed as "idiopathic isolated" clitoromegaly.
      To the best of our knowledge, there has been no detailed report about idiopathic
      clitoromegaly in the literature.

PMID- 15461814
TI  - Intravascular ultrasound to guide the management of intracoronary thrombus: a
      case report.
AB  - Percutaneous coronary intervention can be associated with distal embolization of
      thrombotic material causing myocardial necrosis and infarction. We discuss the
      role of intravascular imaging to guide the use of a distal protection device by
      describing the outcome of a young woman presenting with non-ST elevation
      myocardial infarction. Coronary angiography demonstrated an isolated minor
      stenosis in the proximal left anterior descending coronary artery with slight
      haziness beyond the lesion. Intravascular ultrasound confirmed an extensive
      thrombus overlying a bulky atherosclerotic plaque. A distal filter wire was
      therefore successfully used to reduce the risk of distal embolization. The use of
      intravascular ultrasound in patients presenting with acute coronary syndrome may
      reveal large thrombi that are difficult to image using conventional angiographic
      techniques. Intravascular ultrasound can therefore be used as a tool to select
      lesions requiring distal protection.

PMID- 15461815
TI  - Tuberculous peritonitis in a case receiving continuous ambulatory peritoneal
      dialysis(CAPD) treatment.
AB  - BACKGROUND: Tuberculosis continues to be an important health problem in the
      world. Besides pulmonary involvement extrapulmonary involvement becomes an affair
      in developing countries, even in developed countries. CASE PRESENTATION: A thirty
      six year old male patient was admitted with abdominal pain, diarrhea, nausea,
      vomiting and fever which had started one week before. The patient had been
      followed up with predialisis Chronic Renal Failure(CRF) diagnosis for 4 years and
      receiving continuous ambulatory peritoneal dialysis (CAPD) treatment for 4
      months. In peritoneal fluid, 1600/mm3 cells were detected and 70% of them were
      polymorphonuclear leukocytosis. The patient begun nonspesific antibiotherapy but
      no benefit was obtained after 12 days and peritoneal fluid bacterial cultures
      remained negative. Peritoneal smear was positive for Asid-fast basilli (AFB), and
      antituberculosis therapy was started with isoniazid, rifampicine, ethambutol and
      pyrazinamide. After 15 days his peritoneal fluid cell count was decreased and his
      symptoms were relieved. Peritoneal fluid tuberculosis culture was found positive.
      CONCLUSION: Considering this case, we think that in patients with CAPD catheter
      and peritonitis; when peritoneal fluid leukocytes are high and PMNL are dominant,
      AFB and tuberculosis culture must be investigated besides bacterial culture
      routinely.

PMID- 15461816
TI  - Association of changes in health-related quality of life in coronary heart
      disease with coronary procedures and sociodemographic characteristics.
AB  - BACKGROUND: Few studies have focused on the association between the
      sociodemographic characteristics of a patient with the change in health-related
      quality of life (HRQOL) following invasive coronary procedures, and the results
      remain inconclusive. The objective of the present study was to measure the
      temporal changes in HRQOL of patients with coronary heart disease, and assess how
      these changes are associated with invasive coronary procedures and
      sociodemographic characteristics. METHODS: This was a prospective study of 254
      patients with angina pectoris and 90 patients with acute coronary syndrome. HRQOL
      was assessed with the multi-item scales and summary components of the SF-36, both
      6 weeks and 2 years after baseline hospitalization in 1998. Paired t-tests and
      multiple regression analyses were used to assess temporal changes in HRQOL and to
      identify the associated factors. RESULTS: Physical components of HRQOL had
      improved most during the 2 years following invasive coronary procedures. Our
      findings indicated that patients with angina pectoris who were younger, male, and
      more educated were most likely to increase their HRQOL following invasive
      coronary procedures. When adjusting for baseline HRQOL scores, invasive coronary
      procedures and sociodemographic characteristics did not explain temporal changes
      in patients with acute coronary syndrome, possibly due to higher comorbidity.
      CONCLUSION: Sociodemographic characteristics should be taken into account when
      comparing and interpreting changes in HRQOL scores in patients with and without
      invasive coronary procedures.

PMID- 15461817
TI  - Mechanisms underlying fatigue: a voxel-based morphometric study of chronic
      fatigue syndrome.
AB  - BACKGROUND: Fatigue is a crucial sensation that triggers rest, yet its underlying
      neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of
      chronic fatigue syndrome, which is used as a model to study the mechanisms
      underlying fatigue. METHODS: Using magnetic resonance imaging, we conducted voxel
      based morphometry of 16 patients and 49 age-matched healthy control subjects.
      RESULTS: We found that patients with chronic fatigue syndrome had reduced gray
      matter volume in the bilateral prefrontal cortex. Within these areas, the volume
      reduction in the right prefrontal cortex paralleled the severity of the fatigue
      of the subjects. CONCLUSION: These results are consistent with previous reports
      of an abnormal distribution of acetyl-L-carnitine uptake, which is one of the
      biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Thus,
      the prefrontal cortex might be an important element of the neural system that
      regulates sensations of fatigue.

PMID- 15461818
TI  - Day-to-day variations during clinical drug monitoring of morphine, morphine-3
      glucuronide and morphine-6-glucuronide serum concentrations in cancer patients. A
      prospective observational study.
AB  - BACKGROUND: The feasibility of drug monitoring of serum concentrations of
      morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) during
      chronic morphine therapy is not established. One important factor relevant to
      drug monitoring is to what extent morphine, M6G and M3G serum concentrations
      fluctuate during stable morphine treatment. METHODS: We included twenty-nine
      patients admitted to a palliative care unit receiving oral morphine (n = 19) or
      continuous subcutaneous (sc) morphine infusions (n = 10). Serum concentrations of
      morphine, M6G and M3G were obtained at the same time on four consecutive days. If
      readmitted, the patients were followed for another trial period. Day-to-day
      variations in serum concentrations and ratios were determined by estimating the
      percent coefficient of variation (CV = (mean/SD) x100). RESULTS: The patients'
      median morphine doses were 90 (range; 20-1460) mg/24 h and 135 (range; 30-440)
      mg/24 h during oral and sc administration, respectively. Intraindividual
      fluctuations of serum concentrations estimated by median coefficients of day-to
      day variation were in the oral group for morphine 46%, for M6G 25% and for M3G
      18%. The median coefficients of variation were lower in patients receiving
      continuous sc morphine infusions (morphine 10%, M6G 13%, M3G 9%). CONCLUSION:
      These findings indicate that serum concentrations of morphine and morphine
      metabolites fluctuate. The fluctuations found in our study are not explained by
      changes in morphine doses, administration of other drugs or by time for
      collection of blood samples. As expected the day-to-day variation was lower in
      patients receiving continuous sc morphine infusions compared with patients
      receiving oral morphine.

PMID- 15461820
TI  - Under-representation of developing countries in the research literature: ethical
      issues arising from a survey of five leading medical journals.
AB  - BACKGROUND: It is widely acknowledged that there is a global divide on health
      care and health research known as the 10/90 divide. METHODS: A retrospective
      survey of articles published in the BMJ, Lancet, NEJM, Annals of Internal
      Medicine & JAMA in a calendar year to examine the contribution of the developing
      world to medical literature. We categorized countries into four regions: UK, USA,
      Other Euro-American countries (OEAC) and (RoW). OEAC were European countries
      other than the UK but including Australia, New Zealand and Canada. RoW comprised
      all other countries. RESULTS: The average contribution of the RoW to the research
      literature in the five journals was 6.5%. In the two British journals 7.6% of the
      articles were from the RoW; in the three American journals 4.8% of articles were
      from RoW. The highest proportion of papers from the RoW was in the Lancet (12%).
      An analysis of the authorship of 151 articles from RoW showed that 104 (68.9%)
      involved authorship with developed countries in Europe or North America. There
      were 15 original papers in these journals with data from RoW but without any
      authors from RoW. CONCLUSIONS: There is a marked under-representation of
      countries in high-impact general medical journals. The ethical implications of
      this inequity and ways of reducing it are discussed.

PMID- 15461819
TI  - Evolution and distribution of RNA polymerase II regulatory sites from RNA
      polymerase III dependant mobile Alu elements.
AB  - BACKGROUND: The primate-specific Alu elements, which originated 65 million years
      ago, exist in over a million copies in the human genome. These elements have been
      involved in genome shuffling and various diseases not only through
      retrotransposition but also through large scale Alu-Alu mediated recombination.
      Only a few subfamilies of Alus are currently retropositionally active and show
      insertion/deletion polymorphisms with associated phenotypes. Retroposition occurs
      by means of RNA intermediates synthesised by a RNA polymerase III promoter
      residing in the A-Box and B-Box in these elements. Alus have also been shown to
      harbour a number of transcription factor binding sites, as well as hormone
      responsive elements. The distribution of Alus has been shown to be non-random in
      the human genome and these elements are increasingly being implicated in diverse
      functions such as transcription, translation, response to stress, nucleosome
      positioning and imprinting. RESULTS: We conducted a retrospective analysis of
      putative functional sites, such as the RNA pol III promoter elements, pol II
      regulatory elements like hormone responsive elements and ligand-activated
      receptor binding sites, in Alus of various evolutionary ages. We observe a
      progressive loss of the RNA pol III transcriptional potential with concomitant
      accumulation of RNA pol II regulatory sites. We also observe a significant over
      representation of Alus harboring these sites in promoter regions of signaling and
      metabolism genes of chromosome 22, when compared to genes of information pathway
      components, structural and transport proteins. This difference is not so
      significant between functional categories in the intronic regions of the same
      genes. CONCLUSIONS: Our study clearly suggests that Alu elements, through
      retrotransposition, could distribute functional and regulatable promoter
      elements, which in the course of subsequent selection might be stabilized in the
      genome. Exaptation of regulatory elements in the preexisting genes through Alus
      could thus have contributed to evolution of novel regulatory networks in the
      primate genomes. With such a wide spectrum of regulatory sites present in Alus,
      it also becomes imperative to screen for variations in these sites in candidate
      genes, which are otherwise repeat-masked in studies pertaining to identification
      of predisposition markers.

PMID- 15461821
TI  - The fallacy of enrolling only high-risk subjects in cancer prevention trials: is
      there a "free lunch"?
AB  - BACKGROUND: There is a common belief that most cancer prevention trials should be
      restricted to high-risk subjects in order to increase statistical power. This
      strategy is appropriate if the ultimate target population is subjects at the same
      high-risk. However if the target population is the general population, three
      assumptions may underlie the decision to enroll high-risk subject instead of
      average-risk subjects from the general population: higher statistical power for
      the same sample size, lower costs for the same power and type I error, and a
      correct ratio of benefits to harms. We critically investigate the plausibility of
      these assumptions. METHODS: We considered each assumption in the context of a
      simple example. We investigated statistical power for fixed sample size when the
      investigators assume that relative risk is invariant over risk group, but when,
      in reality, risk difference is invariant over risk groups. We investigated
      possible costs when a trial of high-risk subjects has the same power and type I
      error as a larger trial of average-risk subjects from the general population. We
      investigated the ratios of benefit to harms when extrapolating from high-risk to
      average-risk subjects. RESULTS: Appearances here are misleading. First, the
      increase in statistical power with a trial of high-risk subjects rather than the
      same number of average-risk subjects from the general population assumes that the
      relative risk is the same for high-risk and average-risk subjects. However, if
      the absolute risk difference rather than the relative risk were the same, the
      power can be less with the high-risk subjects. In the analysis of data from a
      cancer prevention trial, we found that invariance of absolute risk difference
      over risk groups was nearly as plausible as invariance of relative risk over risk
      groups. Therefore a priori assumptions of constant relative risk across risk
      groups are not robust, limiting extrapolation of estimates of benefit to the
      general population. Second, a trial of high-risk subjects may cost more than a
      larger trial of average risk subjects with the same power and type I error
      because of additional recruitment and diagnostic testing to identify high-risk
      subjects. Third, the ratio of benefits to harms may be more favorable in high
      risk persons than in average-risk persons in the general population, which means
      that extrapolating this ratio to the general population would be misleading. Thus
      there is no free lunch when using a trial of high-risk subjects to extrapolate
      results to the general population. CONCLUSION: Unless the intervention is
      targeted to only high-risk subjects, cancer prevention trials should be
      implemented in the general population.

PMID- 15461822
TI  - Vaccine candidates derived from a novel infectious cDNA clone of an American
      genotype dengue virus type 2.
AB  - BACKGROUND: A dengue virus type 2 (DEN-2 Tonga/74) isolated from a 1974 epidemic
      was characterized by mild illness and belongs to the American genotype of DEN-2
      viruses. To prepare a vaccine candidate, a previously described 30 nucleotide
      deletion (Delta30) in the 3' untranslated region of DEN-4 has been engineered
      into the DEN-2 isolate. METHODS: A full-length cDNA clone was generated from the
      DEN-2 virus and used to produce recombinant DEN-2 (rDEN-2) and rDEN2Delta30.
      Viruses were evaluated for replication in SCID mice transplanted with human
      hepatoma cells (SCID-HuH-7 mice), in mosquitoes, and in rhesus monkeys.
      Neutralizing antibody induction and protective efficacy were also assessed in
      rhesus monkeys. RESULTS: The rDEN2Delta30 virus was ten-fold reduced in
      replication in SCID-HuH-7 mice when compared to the parent virus. The rDEN-2
      viruses were not infectious for Aedes mosquitoes, but both readily infected
      Toxorynchites mosquitoes. In rhesus monkeys, rDEN2Delta30 appeared to be slightly
      attenuated when compared to the parent virus as measured by duration and peak of
      viremia and neutralizing antibody induction. A derivative of rDEN2Delta30,
      designated rDEN2Delta30-4995, was generated by incorporation of a point mutation
      previously identified in the NS3 gene of DEN-4 and was found to be more
      attenuated than rDEN2Delta30 in SCID-HuH-7 mice. CONCLUSIONS: The rDEN2Delta30
      and rDEN2Delta30-4995 viruses can be considered for evaluation in humans and for
      inclusion in a tetravalent dengue vaccine.

PMID- 15461823
TI  - Radiotherapy fractionation for the palliation of uncomplicated painful bone
      metastases - an evidence-based practice guideline.
AB  - BACKGROUND: This practice guideline was developed to provide recommendations to
      clinicians in Ontario on the preferred standard radiotherapy fractionation
      schedule for the treatment of painful bone metastases. METHODS: A systematic
      review and meta-analysis was performed and published elsewhere. The Supportive
      Care Guidelines Group, a multidisciplinary guideline development panel,
      formulated clinical recommendations based on their interpretation of the
      evidence. In addition to evidence from clinical trials, the panel also considered
      patient convenience and ease of administration of palliative radiotherapy.
      External review of the draft report by Ontario practitioners was obtained through
      a mailed survey, and final approval was obtained from the Practice Guidelines
      Coordinating Committee. RESULTS: Meta-analysis did not detect a significant
      difference in complete or overall pain relief between single treatment and
      multifraction palliative radiotherapy for bone metastases. Fifty-nine Ontario
      practitioners responded to the mailed survey (return rate 62%). Forty-two percent
      also returned written comments. Eighty-three percent of respondents agreed with
      the interpretation of the evidence and 75% agreed that the report should be
      approved as a practice guideline. Minor revisions were made based on feedback
      from the external reviewers and the Practice Guidelines Coordinating Committee.
      The Practice Guidelines Coordinating Committee approved the final practice
      guideline report. CONCLUSION: For adult patients with single or multiple
      radiographically confirmed bone metastases of any histology corresponding to
      painful areas in previously non-irradiated areas without pathologic fractures or
      spinal cord/cauda equine compression, we conclude that: Where the treatment
      objective is pain relief, a single 8 Gy treatment, prescribed to the appropriate
      target volume, is recommended as the standard dose-fractionation schedule for the
      treatment of symptomatic and uncomplicated bone metastases. Several factors
      frequently considered in clinical practice when applying this evidence such as
      the effect of primary histology, anatomical site of treatment, risk of
      pathological fracture, soft tissue disease and cord compression, use of
      antiemetics, and the role of retreatment are discussed as qualifying
      statements.Our systematic review and meta-analysis provided high quality evidence
      for the key recommendation in this clinical practice guideline. Qualifying
      statements addressing factors that should be considered when applying this
      recommendation in clinical practice facilitate its clinical application. The
      rigorous development and approval process result in a final document that is
      strongly endorsed by practitioners as a practice guideline.

PMID- 15461824
TI  - Polyadenylation of ribosomal RNA by Candida albicans also involves the small
      subunit.
AB  - BACKGROUND: Candida albicans is a polymorphic fungus causing serious infections
      in immunocompromised patients. It is capable of shifting from yeast to
      germinating forms such as hypha and pseudohypha in response to a variety of
      signals, including mammalian serum. We have previously shown that some of the
      large 25S components of ribosomal RNA in Candida albicans get polyadenylated, and
      this process is transiently intensified shortly after serum exposure just prior
      to the appearance of germination changes. RESULTS: We now present data that this
      process also involves the small 18S subunit of ribosomal RNA in this organism.
      Unlike the large 25S subunit, polyadenylation sites near the 3' end are more
      variable and no polyadenylation was found at the reported maturation site of 18S.
      Similar to 25S, one or more polyadenylated mature sized 18S molecules get
      intensified transiently by serum just prior to the appearance of hypha.
      CONCLUSIONS: The transient increase in polyadenylation of both the large and the
      small subunits of ribosomal RNA just prior to the appearance of hypha, raises the
      possibility of a role in this process.

PMID- 15461825
TI  - Morphine for elective endotracheal intubation in neonates: a randomized trial
      [ISRCTN43546373].
AB  - BACKGROUND: Elective endotracheal intubations are still commonly performed
      without premedication in many institutions. The hypothesis tested in this study
      was that morphine given prior to elective intubations in neonates would decrease
      fluctuations in vital signs, shorten the duration of intubation and reduce the
      number of attempts. METHODS: From December 1999 to September 2000, infants of all
      gestations admitted to a level III neonatal intensive care unit and requiring an
      elective endotracheal intubation were randomly assigned to receive morphine 0.2
      mg/kg IV or placebo 5 minutes before intubation. Duration of severe hypoxemia
      (HR< 90/min and Sp02<85%), duration of procedure, duration of hypoxemia
      (Sp02<85%), number of attempts and change in mean blood pressure were compared
      between groups. RESULTS: 34 infants (median 989 g and 28 weeks gestation) were
      included. The duration of severe hypoxemia was similar between groups. Duration
      of procedure, duration of hypoxemia, number of attempts and increases in mean
      blood pressure were also similar between groups. 94% of infants experienced
      bradycardia during the procedure. CONCLUSION: We failed to demonstrate the
      effectiveness of morphine in reducing the physiological instability or time
      needed to perform elective intubations. Alternatives, perhaps with more rapid
      onset of action, should be considered.

PMID- 15461826
TI  - Psychosocial correlates with depressive symptoms six years after a first episode
      of psychosis as compared with findings from a general population sample.
AB  - BACKGROUND: Depression is frequently occurring during and after psychosis. The
      aim of this study was to analyze if the psychosocial characteristics associated
      with depression/depressive symptoms in the late phase of a first episode
      psychosis (FEP) population were different compared to persons from the general
      population. METHODS: A questionnaire was sent out to all individuals six years
      after their FEP and to a general population sample. Depressive symptoms were
      recorded using a self-rating scale, the Major Depression Inventory. RESULTS:
      Formerly FEP persons had a higher representation of depressive
      symptoms/depression, unemployment, financial problems and insufficient social
      network. Depressive symptoms/depression were found to be associated with
      psychosocial problems. An age and gender effect was found in the general
      population, but not in the FEP sample. When the psychosocial characteristics were
      taken into account there were no association between having had FEP and
      depressive symptoms. CONCLUSIONS: The association between having been a FEP
      patient and depressive symptoms/depression disappeared when negative social
      aspects were taken into account.

PMID- 15461827
TI  - [Study on the method of first-aid for critical care on spot of disasters should
      be strengthened].

PMID- 15461828
TI  - [Comment on contentious problems of multiple organ dysfunction syndrome].

PMID- 15461829
TI  - [Application of corticosteroid in the treatment of septic shock].

PMID- 15461830
TI  - [Studies on the expression of mRNA of anti- and pro-inflammatory cytokines in
      acute lung injury induced by lipopolysaccharide in rat].
AB  - OBJECTIVE: To study the role of pro-inflammatory cytokines including tumor
      necrosis factor-alpha(TNF-alpha), interleukin-1beta(IL-1beta), IL-6, and anti
      inflammatory cytokines including IL-4, IL-10, and IL-13 in acute lung
      injury(ALI). METHODS: Reverse transcription-polymerase chain reaction(RT-PCR)
      were used to assess the expressions of mRNA of TNF-alpha, IL-1beta, IL-6, IL-4,
      IL-10 and IL-13 in the lung tissue after lipopolysaccharide challenge. RESULTS:
      The expression of TNF-alpha mRNA was seen to peak at 1 hour and IL-6 mRNA at 4
      hours in lung tissue after the challenge. The highest expression of mRNA of other
      cytokines, such as IL-1beta, IL-4, IL-10 and IL-13 in lung tissue appeared 2
      hours after LPS-induced lung injury. CONCLUSION: TNF-alpha is an early presenting
      cytokine in ALI, and IL-6 may play an important role in delayed development of
      ALI. The over-expression of anti-inflammatory cytokines IL-4, IL-10 and IL-13 may
      act as promoters rather than protectors in amplification of inflammatory process.

PMID- 15461832
TI  - [Establishment of a mobile intensive care unit].
AB  - OBJECTIVE: To discuss the experience of establishment of a mobile intensive care
      unit (ICU) for emergency treatment following astronaut flight, disaster, and
      regional war. METHODS: The data from both foreign and our countries as well as
      our own clinical experience of first-aid were reviewed, and a mobile ICU was
      established, including the equipment, supply of drugs, training, and
      organization. RESULTS: The mobile ICU was set up at the site of landing of the
      first Chinese astronaut, and proved to be efficient. The new model could be
      expected to be prompt in first-aid for casualties in disasters and warfare.
      CONCLUSION: The first-aid on spot of casualties might reduce the rates of
      invalidity and mortality during disasters and regional war.

PMID- 15461833
TI  - [High mobility group box-1 protein activates Janus kinase-signal transducer and
      activator of transcription pathway in rat peritoneal macrophages].
AB  - OBJECTIVE: To investigate the potential signal transduction mechanism in high
      mobility group box-1 protein (HMGB1)-induced inflammatory response in rat
      peritoneal macrophages. METHODS: Peritoneal macrophages obtained from male Wistar
      rats were incubated for 3 days before they were stimulated by HMGB1 (10
      microg/ml). At various time points after HMGB1 stimulation, macrophages were
      denatured directly in cell culture flasks to detect activation of Janus kinase-2
      (JAK2), signal transducer and activator of transcription-1 (STAT1) and STAT3 by
      immunoprecipitation, Western blotting and electrophoretic mobility shift assay,
      respectively. RESULTS: HMGB1 stimulation could activate STAT1 and STAT3 in
      peritoneal macrophages in 2 hours, among them the activation of STAT3 appeared to
      be the quickest, peaking as early as 10 minutes after stimulation. But no marked
      change in JAK2 activity was observed within 2 hours following HMGB1 stimulation.
      CONCLUSION: These data suggest that Janus kinase-signal transducer and activator
      of transcription pathway might be involved in regulation of HMGB1-induced
      inflammatory response in peritoneal macrophages.

PMID- 15461835
TI  - [Effect of alpha-melanocyte stimulating hormone on the apoptosis of the vascular
      endothelial cell of the lung in two-hit acute respiratory distress syndrome in
      rat].
AB  - OBJECTIVE: To investigate the effect of alpha-melanocyte stimulating hormone
      (alpha-MSH) on the apoptosis of the vascular endothelial cells of the lung in
      acute respiratory distress syndrome (ARDS) reproduced with acute hemorrhagic
      shock followed by intratracheal lipopolysaccharide (LPS, two-hit model) in rat.
      METHODS: Ten male Sprague Dawley rats, weighing (33.7+/-2.5) g, were randomly
      divided into two groups (A and B) with 5 in each group. All rats were
      anesthesized and ventilated mechanically with fractional concentration of
      inspired oxygen(FiO(2)) of 0.5, breath rate 100 times/min, tidal volume(V(T)) 12
      ml/kg and inspiratory/expiratory ratio (I/E) 1:15. The blood was withdrawn to
      induce hemorrhagic shock via the carotid artery until blood pressure reached
      (45+/-5) mm Hg (1 mm Hg=0.133 kPa), which was maintained for 1 hour, and the shed
      blood and Ringer's lactate in volume equal to the shed blood were reinfused in 2
      hours for resuscitation. Afterwards, LPS was given via the tracheal (200
      microg/kg, in 500 microl normal saline) to establish the ARDS model. Group A was
      ARDS control group, group B was alpha-MSH administration group. alpha-MSH was
      intravenously administrated simultaneously, 3 hours and 6 hours after LPS given,
      the dosage was 17 mg/kg at each time point. The rats were sacrificed at 9 hours
      after LPS challenge, and the lung tissue was examined with microscope and
      electron microscope to observe the pathological changes and apoptosis of the
      vascular endothelial cells. RESULTS: In ARDS control group, remarkable
      infiltration of inflammatory cells was found in the alveoli, and the apoptosis of
      the vascular endothelial cells had developed to late stage. In alpha-MSH
      treatment group, few inflammatory cells were found in the alveoli, and the
      apoptosis of the endothelial cells was still in an early stage. CONCLUSION: alpha
      MSH could inhibit the apoptosis of the vascular endothelial cells of the lung in
      the two-hit ARDS in rats. Therefore, it might have a protective effect on the
      lung after hemorrhagic shock and endotoxin challenge.

PMID- 15461836
TI  - [Value of blinded sampling methods in the pathogenic diagnosis of ventilator
      associated pneumonia].
AB  - OBJECTIVE: To evaluate the diagnostic value of blinded protected specimen brush
      and quantitative culture (BPSB-QC) in the pathogenic diagnosis of ventilator
      associated pneumonia (VAP). METHODS: A prospective, self-controlled clinical
      trial was conducted during a 36-month period. QC of paired samples of BPSB and
      PSB via a fiberoptic bronchoscopy (FOB- PSB) in a total of 54 patients during 125
      suspected episodes of VAP was compared. The sensitivity and accuracy, as well as
      the concordance between BPSB-QC and FOB-PSB-QC result in 48 patients with 106
      episodes of VAP were assessed. Both BPSB-QC and FOB-PSB-QC greater than 103
      cfu/ml (positive cutoff) was considered diagnostic of VAP. RESULTS: Forty-eight
      patients with 106 episodes were considered to have VAP (84.8%). The accuracy of
      BPSB-QC and FOB-PSB-QC were 80.8% (101/125) and 83.2% (104/125), respectively.
      The rate of complete concordant results was high (75.2%) for BPSB-QC and FOB-PSB
      QC. The pathogenic diagnostic agreement between the two techniques was 84.8%
      (106/125). There were no significant differences with regard to site of pneumonia
      and positive diagnostic rate between the two techniques. CONCLUSION: BPSB-QC has
      similar accuracy and same feasibility compared with FOB-PSB-QC which was commonly
      primarily used in the pathogenic diagnosis of VAP, and that its use is
      substantially simpler, safe and cost saving, especially when FOB technique is not
      available.

PMID- 15461837
TI  - [Effect of sustained inflation on inflammatory response of extra pulmonary organs
      in acute respiratory distress syndrome in rabbit].
AB  - OBJECTIVE: To evaluate the influence of sustained inflation (SI) on inflammatory
      response of extra pulmonary organs in acute respiratory distress syndrome (ARDS)
      in rabbit. METHODS: The ARDS rabbit model were replicated by saline alveoli
      lavage. The rabbits were randomly divided into four groups: 1. normal group; 2.
      ARDS group; 3. low-volume(V(T)) + best end-expiratory pressure group (LVBP): V(T)
      6 ml/kg, PEEP 2 cm H(2)O(1 cm H(2)O=0.098 kPa) greater than the pressure of lower
      inflection point in pressure-volume curve (Pinf); 4. SI group: same settings as
      LVBP group plus SI performed every hour. After 4 hours of ventilation, liver and
      intestine homogenates were prepared to assay tumor necrosis factor (TNF)-alpha
      and interleukin(IL)-10 levels by enzyme-linked immunoadsorbent assay and their
      mRNA expression by reverse transcription-polymerase chain reaction.
      Myeloperoxidase (MPO) and malondialdehyde (MDA) were assessed at the same time.
      RESULTS: In SI group, TNF-alpha mRNA expression in the liver and intestine
      tissues (24.82+/-7.88 and 25.06+/-10.57) were decreased significantly compared
      with ARDS (36.88+/-6.83 and 36.48+/-8.23) and LVBP groups (42.34+/-8.55 and
      37.59+/-10.63, all P<0.05). The expression of IL-10 mRNA in the liver and
      intestine of rabbits in SI group (17.31+/-5.72 and 10.90+/-3.30) was lower than
      that of ARDS (24.64+/-3.85 and 24.31+/-7.69) and LVBP group (25.03+/-9.38 and
      21.83+/-7.34, all P<0.05) significantly. In SI group, the levels of TNF-alpha and
      IL-10 in liver and intestine tissue were similar to that of the other groups. The
      contents of MPO and MDA had no difference compared with the other groups too.
      CONCLUSION: SI can down-regulate inflammatory mediator expression of extra
      pulmonary organs in rabbits with ARDS, and it may inhibit the inflammatory
      response in extra pulmonary organs.

PMID- 15461840
TI  - [Inflammatory injurious effect of angiotensin II on pulmonary microvascular
      endothelium in rat].
AB  - OBJECTIVE: To investigate the effects of angiotensin II (AngII) and its receptors
      on monolayer permeability of pulmonary microvascular endothelial cells in rat.
      METHODS: The following examinations were done on cultured rat pulmonary
      microvascular endothelial cells (RPMVECs). 1. Micro-filter was used to assay the
      variations of lipopolysaccharide (LPS)-induced increased RPMVECs monolayer
      permeability coefficient (Kf) in different periods. 2. Effect of angiotensin II
      on LPS-induced permeability injury to the endothelium, and preventive effects of
      angiotensin II type 1 receptor antagonist (Sar1, Ile8)-Ang II. RESULTS: LPS
      increased RPMVECs monolayer permeability compared with normal control, and AngII
      exacerbated LPS-induced RPMVECs monolayer permeability significantly. This
      synergistic effect was significantly prevented by the addition of (Sar1, Ile8 )
      Ang II. CONCLUSION: AngII and LPS have synergistic injurious effects to the
      pulmonary microvascular endothelium in rat, and AngII exacerbates increase in LPS
      induced RPMVECs monolayer permeability. This synergistic effect is significantly
      prevented by the addition of (Sar1, Ile8)-Ang II.

PMID- 15461841
TI  - [Protective effect of N-acetylcysteine on acute lung injury caused by exposure to
      rocket liquid propellant].
AB  - OBJECTIVE: To investigate the protective effect and its mechanisms of N
      acetylcysteine (NAC) on acute lung injury (ALI) caused by exposure to high
      concentration rocket liquid propellants asymmetrical dimethylhydrazine (UDMH) and
      dinitrogen tetroxide (N(2)O(4)). METHODS: Forty-two rats were randomly divided
      into three groups: the control group, the exposure group and the exposure plus
      the treatment group (NAC group). The rats of the latter two groups were exposed
      to UDMH 0.98 mg/L for 10 minutes and then N(2)O(4) 0.19 mg/L for another 10
      minutes. After the exposure, the NAC group rats received immediately 150 mg/kg of
      NAC intravenously, and rein forced by intraperitoneal injection of NAC with a
      dose of 50 mg/kg 3 hours after the intravenous injection. The rats of other group
      were treated with saline in equal volume. All rats were killed after 6 hours. The
      lung wet to dry ratio (W/D ), the contents of lactate dehydrogenase (LDH) and
      total protein in bronchoalveolar lavage fluid (BALF), the activities of
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissue,
      and the malondialdehyde (MDA) of plasma were measured. Pathological examination
      was performed. RESULTS: The lung W/D ratio, the LDH and total protein in BALF,
      and the MDA of plasma were increased in the exposure group, while the activities
      of SOD and GSH-Px in lung tissue were decreased. The histopathology of the rats
      of exposure groups showed that there was exudation within alveolar spaces and
      prominent interstitial thickening of septa. In the NAC group, the values of the
      above findings were lowered, and the degree of lung injury was alleviated in
      histopathology. The lung W/D were negatively correlated with the activities of
      SOD and GSH-Px in lung tissue, and the correlation coefficient were-0662 (P<0.01)
      and -0707(P<0.01) respectively. CONCLUSION: The administration of NAC appears to
      attenuate the injury to the lung after an exposure to UDMH and N(2)O(4) in high
      concentration, and the antioxidant activity of NAC may be responsible for the
      protective effect.

PMID- 15461843
TI  - [Clinical investigation of application of lung biopsy in the diagnosis of diffuse
      pulmonary interstitial disease].
AB  - OBJECTIVE: To evaluate the application of lung biopsy in the diagnosis of diffuse
      pulmonary interstitial disease (DPID). METHODS: The data of lung biopsy from 17
      cases with uncertain DPID obtained during the period of July 1997 and December
      2002 were retrospectively analysed. RESULTS: All the cases were diagnosed by
      pathology. Three of them were diagnosed as sarcoidosis. Two were pulmonary
      alveolar proteinosis. One with usual interstitial pneumonia (UIP), one with
      bronchiolitis obliterans and organizing pneumonia, one with nonspecific
      pneumonia, one with Castleman's disease, one with pulmonary lymph angio
      leiomyomatosis, two with bronchioalveolar carcinoma, one as rheumatoid pulmonary
      fibrosis complicated with pulmonary squamous cancer and locally metastasis in
      lungs, two as pulmonary lymphangitic carcinomatosis, one as lung squamous cancer
      with pulmonary lymphangitic metastasis, and one with primary pulmonary
      paraganglioma. CONCLUSION: Harvest of lung tissue directly by biopsy could be the
      most useful diagnostic method for DPID, and it is a highly valuable diagnostic
      tool for those patients whose diagnosis is uncertain with routine chest film and
      high resolution computed tomography.

PMID- 15461845
TI  - [Study on effect of dexamethasone on the expression of matrix metalloproteinase
      and its tissue inhibitors in hyperoxia-induced lung injury].
AB  - OBJECTIVE: To observe the effect of dexamethasone on the mRNA expression of
      matrix metalloproteinase (MMPs) and tissue inhibitor of metalloproteinase (TIMPs)
      in the lung tissue and to explore the protective mechanism of dexamethasone in
      hyperoxia-induced lung injury. METHODS: Thirty-two two-week old Wistar rats were
      randomly divided into atmospheric-air group (n=16) and hyperoxia group (n=16).
      After 7 days of continuous exposure to high concentration O (2)(>95%), the lung
      wet/dry(W/D) ratio, the protein content in bronchoalveolar lavage fluid(BALF) and
      histopathological changes of the lung were measured in 16 rats(8 in each group).
      The lung tissue specimens of the other 16 rats were cultured, 8 among which
      served as atmospheric-air control group, the remainder in the hyperoxia group
      were divided into hyperoxia control group,hyperoxia+dexamethasone (1 x 10(-8)
      mol/L) group, hyperoxia+dexamethasone (1 x 10(-6) mol/L) group, and
      hyperoxia+dexamethasone (1 x 10(-4) mol/L) group. Eight samples were examined in
      each group. After cultured for 24 hours, the lung tissue were collected and its
      mRNA expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 were determined by reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: 1. Pulmonary edema,
      hemorrhage and extensive inflammatory cells infiltration were observed in
      hyperoxia group, but no such changes were found in the atmospheric-air group. The
      lung W/D and the protein content in BALF in hyperoxia group were significantly
      higher than those in atmospheric air groups. 2. The mRNA expressions of MMP-2,
      MMP-9, TIMP-1, TIMP-2 and the ratio of MMP-2/TIMP-2, MMP-9/TIMP-1 were
      significantly higher in the hyperoxic group than those in the atmospheric-air
      group. 3. Dexamethasone could down-regulate the mRNA expressions of MMP-2 and MMP
      9 in a concentration dependent manner. The mRNA expressions of TIMP-1, TIMP-2
      also could be reduced by dexamethasone. Decreasing ratios of MMP-2/TIMP-2 and MMP
      9/TIMP-1 were found in correlation with increasing concentration of
      dexamethasone. CONCLUSION: Dexamethasone can reduce the mRNA expressions of MMPs
      as well as regulate the balance of MMPs/TIMPs, which may be one of the mechanism
      of its protective effect on hyperoxia-induced lung injury.

PMID- 15461846
TI  - [Change in Toll-like receptor 4 expression on interstitial macrophages in acute
      lung injury].
AB  - OBJECTIVE: To observe changes in the level of Toll-like receptor 4 (TLR4) mRNA
      and the expression of TLR4 protein in interstitial macrophages in serious
      thoracic injury. METHODS: A rat model of severe thoracic trauma was
      reproduced,then interstitial macrophages were isolated and collected by enzymatic
      digestion before and after trauma cultured. TLR4 mRNA and the expression of TLR4
      protein were measured by Northern and Western blotting before trauma and 2, 4, 8,
      16, 24 hours after trauma. RESULTS: A stable and reliable severe thoracic trauma
      model was successfully reproduced with 400 kPa impact on the up-right chest of
      rat by a multiple-function collision apparatus. The expression was up-regulated
      by trauma and the highest expression of interstitial macrophages occurred 8, 16
      hours after the trauma, and returned to normal range at 24 hours. CONCLUSION: The
      up-regulation of TLR4 might participate in the pathological process of excessive
      inflammation after trauma to the lung.

PMID- 15461847
TI  - [Study on molecular mechanisms of indirect suppression of albumin mRNA expression
      of hepatocytes by lipopolysaccharide in rat].
AB  - OBJECTIVE: To explore the molecular mechanisms of relationship between the
      decreased expression of albumin gene of the cultured hepatocytes by
      lipopolysaccharide (LPS) and cytokines. METHODS: As an inhibitor of protein
      synthesis, cycloheximide (CHX) could inhibit the LPS-induced synthesis of
      cytokines. Therefore, the culture system pretreated with CHX could exclude the
      influence of cytokines on the regulation of albumin gene expression, then it
      might prove that LPS induced down-regulation of expression of albumin gene was a
      through cytokine-dependent pathway. The concentrations of interleukin (IL-6) and
      tumor necrosis factor-alpha(TNF -alpha) in the supernatant were also assayed.
      RESULTS: The expression of albumin mRNA is inhibited significantly by LPS. CHX
      could block the pathway of LPS-induced down-regulation of expression of albumin
      gene at least at the transcription level. And the prevention was in a dose
      related manner. The increase of IL-6 and TNF-alpha induced by LPS was inhibited
      by CHX(both P<0.05). CONCLUSION: The results suggest that LPS can indirectly
      inhibit the transcription of albumin gene through cytokines such as IL-6 and TNF
      alpha.

PMID- 15461848
TI  - [Effects of norepinephrine on the therapeutic effect of nitric oxide inhalation
      in the treatment of acute respiratory distress syndrome in goat].
AB  - OBJECTIVE: To observe effects of norepinephrine (NE) on the therapeutic effects
      of nitric oxide (NO) inhalation in goats with endotoxin-induced acute respiratory
      distress syndrome (ARDS). METHODS: A model of septic ARDS was reproduced by an
      intravenous infusion of low dose endotoxin in six goats, and then these animals
      were treated with 40 x 10(-6) NO inhalation. After 30 minutes, intravenous
      infusion of NE in dose of 0.5 microg x kg(-1) x h(-1) was given. The dynamic
      changes in gas exchange and hemodynamics were measured with the aid of Swan-Ganz
      catheter and arterial blood gas analysis before and after the onset of ARDS, 30
      minutes after NO inhalation and administration of NE. RESULTS: Inhalation of NO
      rapidly reduced mean pulmonary arterial pressure (MPAP), increased PaO(2),
      decreased alveolar-arterial partial pressure of oxygen difference (P (A-a) O(2))
      and intrapulmonary shunt fraction (Qs/Qt) in septic ARDS goats. These changes
      were more pronounced when NE was given compared with NO inhalation alone. The
      combination of NO inhalation and NE infusion resulted in an increase in mean
      arterial pressure. CONCLUSION: Norepinephrine enhances the beneficial effect of
      nitric oxide inhalation on lung gas exchange in goats with endotoxin induced
      acute respiratory distress syndrome.

PMID- 15461855
TI  - Cytokines and the brain.

PMID- 15461856
TI  - Cytokines and allergic disorders: revisited study.

PMID- 15461857
TI  - Alternative sources of fibrinolytic, anticoagulative, antimicrobial and
      anticancer molecules.
AB  - The medicinal properties of earthworms in various remedies date back to 1340 A.D.
      and have been extended to other countries and cultures. Assays of tissue
      homogenates of earthworm (Eisenia foetida) have revealed a glycolipoprotein
      mixture referred to as G-90 that is composed of macromolecules with medical and
      pharmaceutical applications. There are several functions attributed to G-90:
      possession of several growth factors that: stimulate proliferation in cell
      cultures, contain an insulin like growth factor (IGF like), an immunoglobulin
      like growth factor (IgFG-like), possess two serine peptidases with a tyrosine
      code and epidermal growth factor (EGF). In contrast, G-90 exerts strong
      fibrinolytic and anticoagulative activity capable of lysing fibrin clots. Actions
      of these two properties are dependent upon concentration. Anti-coagulative
      activity also depends upon the kind of anticoagulants (G-90, PI, PII). G-90 can
      also act as antioxidant, exert antimicrobial activities in vitro and in vivo. The
      bacteriostatic effect is significantly greater for non-pathogenic species.
      Finally G-90 also participates in tissue regeneration and wound healing. Taken
      together, components of earthworms could be tested in certain clinical trials.

PMID- 15461859
TI  - Development of a clinical grade procedure for generation of mRNA transfected
      dendritic cells from purified frozen CD34(+) blood progenitor cells.
AB  - Enriched CD34(+) peripheral blood progenitor cells (PBPC) are frequently used as
      stem cell support in cancer patients following high dose therapy. Since precursor
      dendritic cells (DCs) originate from haematopoietic progenitor cells, purified
      CD34(+) cells might also serve as starting cells for ex- vivo production of DC.
      In the present study we developed a clinical grade procedure for ex- vivo
      production of DC derived from enriched CD34(+) cells. Different concentrations of
      CD34(+) cells were grown in gas-permeable Teflon bags with different serum-free
      and serum-containing media supplemented with GM-CSF, IL-4, TNF-alpha, SCF, Flt-3L
      and INF-alpha. Serum-free CellGroSCGM medium for 7 days followed by CellGroDC
      medium in 7 days gave the same results as serum-containing medium. After
      incubation the cultured cells containing immature DCs were concentrated and
      transfected with tumour mRNA from human prostate cancer cell lines employing a
      highly efficient electroporation procedure. Thawed transfected DCs were able to
      elicit primary T-cell responses in vitro against antigens encoded by the prostate
      cancer mRNA as shown by ELISPOT assay using mock-transfected DCs as control. Our
      results show that frozen enriched CD34(+) cells can be an alternative and
      efficient source for production of DCs for therapeutic purpose.

PMID- 15461858
TI  - Photodynamic therapy targeted to pathogens.
AB  - Photodynamic therapy (PDT) employs a non-toxic dye termed a photosensitizer (PS)
      together with low intensity visible light, which, in the presence of oxygen,
      produce cytotoxic species. PS can be targeted to its destination cell or tissue
      and, in addition, the irradiation can be spatially confined to the lesion giving
      PDT the advantage of dual selectivity. This promising approach can be used for
      various applications including microbial inactivation and the treatment of
      infections. Resistance to PDT has not been shown and multiantibiotic-resistant
      strains are as easily killed as naive strains. It is known that Gram (+) bacteria
      are more sensitive to PDT as compared to Gram (-) species. However, the use of
      cationic PS or agents that increase the permeability of the outer membrane allows
      for the effective killing of Gram (-) organisms. Some PS have an innate positive
      charge, but our approach is to link PS to a cationic molecular vehicle such as
      poly-L-lysine. This modification dramatically increases PS binding to and
      penetrating through the negatively charged bacterial permeability barrier. Due to
      focused light delivery the use of PDT is possible only for localized infections.
      Nonetheless numerous diseases can be treated. Selectivity of the PS for microbes
      over host cells, accurate delivery of the PS into the infected area, and PDT dose
      adjustment help minimize side effects and give PDT an advantage over conventional
      therapy. There are only a few reports about the use of antimicrobial PDT in
      animal models and clinical trials. We have used genetically modified
      bioluminescent bacteria to follow the effect of PDT in infected wounds, burns,
      and soft tissue infections in mice. Not only were bacteria infecting wounds,
      burns, and abscesses killed, but mice were saved from death due to sepsis and
      wound healing was improved.

PMID- 15461860
TI  - A scavenger role for nitric oxide in the aged rat kidney.
AB  - Progressive ageing is associated with an increment of biomolecules modified
      through oxidation as a result of the action of free radicals deriving from
      reactive oxygen species that attack biomolecules. During ageing many alterations
      of renal functions have been reported. Renal ageing is associated with a
      progressive decline of glomerular filtration, renal blood flow and augmented
      vascular resistance. The kidney is a very important source of inducible nitric
      oxide synthase (iNOS) in both epithelial and vascular structures. In this study
      we have investigated mRNA and protein iNOS expression and localization and nitric
      oxide (NO) production in young and aged rats. An increased expression of iNOS
      occurs in rat kidney during ageing. In the aged rat, an increase in the values of
      both iNOS-RNA and iNOS protein was observed through rtPCR and Western blot
      analysis. The activities of three isoforms of NOS were also seen. In the aged rat
      kidney the production of NO decreased, due to the reduction of the activities of
      the three NOS. This suggests that in the aged rat a progressive increase of
      superoxide anion does not imply an increase in the production of NO which
      functions as a scavenger molecule, causing oxidative stress with accumulation of
      reactive oxygen species (ROS).

PMID- 15461861
TI  - Cyclooxygenase-2 expression in oral squamous cell carcinoma.
AB  - Cyclooxygenase (COX), the key enzyme in prostaglandin cascade, is expressed in
      two isoforms: the constitutive COX-1 and the inducible COX-2. Hyper-expression of
      COX-2 has been implicated in the pathogenesis of colon-rectal cancer in humans
      but it appears to play a significant role as a tumour progression factor also in
      other forms of human cancer, including oral cancer. The aim of this study was to
      analyze the expression of COX-2, at the protein level, in 45 cases of oral
      squamous cell carcinoma. Standard immunohistochemical streptavidin-biotin
      peroxidase analysis was carried out with highly specific antibody against human
      COX-2 and cell specific markers, in 45 oral squamous cell carcinomas. Our study
      revealed a moderate to high COX-2 expression in 35 out of the 45 oral squamous
      cell carcinoma specimens (77.8%). COX-2 expression appeared particularly abundant
      in the superficial ulcerated layers of relatively well differentiated carcinomas.
      However, we were unable to assess any statistically significant association
      between COX-2 hyper-expression and tumor site, tumor grading, tumor size,
      presence of lymph node metastases, tumor stage and age at onset, respectively.
      Interestingly, COX-2 expression was detected not only in areas of epithelial
      dysplasia adjacent to the primary layers (86% of the cases) but also in normal
      appearing epithelium at the boundaries of squamous cell carcinoma (77%),
      indicating a possible involvement in tumour progression by the apparently normal
      tissue surrounding the lesion. Moreover, intense COX-2 staining was observed in
      endothelial cells of intra-tumour vessels and extra-tumour vessels adjacent to
      the tumour nests, in a high proportion of cases (82%). COX-2 positivity was
      associated with CD34 and VEGF positivity, indicating that these vessels were
      probably neo-formed ones. From this study as well as from other works, it appears
      that indeed COX-2 is over-expressed in this important human malignancy. However,
      further studies are necessary to understand the exact magnitude of this over
      expression and, mostly, the possible role of COX-2 in the pathogenesis and
      progression of oral cancer.

PMID- 15461862
TI  - Augmentation of macrophage phagocytosis by modified arabinoxylan rice bran (MGN
      3/biobran).
AB  - MGN-3/Biobran, modified arabinoxylan rice bran, has been shown to be a potent
      biological response modifier (BRM) as manifested by stimulation of different arms
      of the immune system such as NK, T and B cells; however, its effect on
      macrophages has not yet been studied. The effects of MGN-3 on macrophage function
      was examined in vitro using 3 models: human macrophage cell line U937, murine
      macrophage cell line RAW264.7, and murine peritoneal macrophages (P-M phi).
      Treatment with MGN-3 resulted in an increase in the percentages of attachment and
      phagocytosis of yeast by macrophages. The effect depends on the type of
      macrophage and the dose of MGN-3 applied. Macrophages also demonstrated
      enhancement in their spreading ability, post treatment with MGN-3. Results also
      showed that MGN-3, in a dose dependent manner (1, 10,100 microg/ml),
      significantly induced high levels of production of cytokines: TNF-alpha; and IL
      6. In addition, MGN-3 significantly increased nitric oxide (NO) production. This
      data demonstrates that MGN-3 is a potent inducer of phagocytic function by
      macrophage, and suggests that MGN-3 is a useful agent for fighting microbial
      infection.

PMID- 15461863
TI  - Sphingolipid microdomains mediate CD38 internalization: topography of the
      endocytosis.
AB  - Plasma membranes of several cell types contain specialized microdomains (or lipid
      rafts) enriched in sphingolipids, cholesterol, sphingomyelin, and glycosyl
      phosphatidylinositol-anchored proteins. These membrane domains are characterized
      by detergent insolubility at low temperatures and low buoyant density. Human CD38
      is the prototype of a gene family encoding surface molecules endowed with
      multiple functional activities. The endocytosis of the human CD38 molecule has
      been investigated in normal lymphocytes and in a number of leukemia- and lymphoma
      derived cell lines demonstrating that internalization after CD38 ligation is a
      reproducible event involving only a fraction of the whole amount of the surface
      molecule. This study reports the results obtained by conventional, confocal, and
      electron microscopy on the effects induced by the engagement of the molecule with
      agonistic mAb, reproducing the signals mediated by its natural ligand. The
      results demonstrate that the endocytosis induced as consequence of CD38 ligation
      is preceded by a thorough rearrangement of the cell surface with formation of
      glycosphingolipid- and cholesterol-rich plasma membrane microdomains. These data
      suggest that specialized raft microdomains might be the plasma membrane structure
      through which CD38 translocates at intracellular level. The CD38/lipid
      interactions during the coated pit formation trigger a process that generate
      membrane curvature, considered as the first step of CD38 endocytosis. Moreover,
      ultrastructural studies show that early CD38(+) endosomes are pleiomorphic and
      contain cisternal and vesicular regions. Late endosomes exhibit a complex
      organisation, containing uncoupled CD38-ligand multivesicular- or multilamellar
      regions.

PMID- 15461864
TI  - Detection of Chlamydia pneumoniae in atherosclerotic coronary arteries.
AB  - Chlamydia pneumoniae has recently been associated with the development of
      coronary heart diseases by sero-epidemiological studies and by direct detection
      of the organism in atherosclerotic tissues. The aim of our study was to employ a
      semi-nested PCR approach to investigate the presence of C. pneumoniae in both
      normal and atherosclerotic coronary arteries of humans obtained at autopsy.
      Moreover, we have evaluated the role of infection with C. pneumoniae in relation
      to the extent of coronary atherosclerosis. One hundred and eighty coronary artery
      specimens were collected at autopsy from 60 consecutive subjects (three arterial
      segments from each subject). Atherosclerosis in each arterial segment was graded
      histologically by the Stary classification. Thirty normal coronary arteries were
      also taken at autopsy as control. PCR results evidenced the presence of C.
      pneumoniae DNA in atherosclerotic coronary arteries in 19 (31.7%) of 60 subjects
      examined, while none of the 30 subjects with non-atherosclerotic tissues was
      positive (p=0.001). Moreover, of the 180 atherosclerotic specimens examined, C.
      pneumoniae DNA was detected in 3.4% (2/59) of mild atherosclerotic lesions, and
      in 14.0% (17/121) of advanced atherosclerotic lesions (p=0.05). Our results
      demonstrate that the presence of C. pneumoniae DNA may be associated with the
      severity of coronary atherosclerosis.

PMID- 15461865
TI  - HLA and hypocomplementemia: the disadvantage of carrying the HLA-B35 and the
      silent alleles of the C4 complement component.
AB  - Hypocomplementemia is an extremely complex phenomenon: we devoted our attention
      to its immunogenetic basis, particularly to the HLA haplotypes involved and to
      the study of C4 polymorphic genes. With this in mind we analyzed a group of
      unrelated patients with hypocomplementemia and 15 families suffering from
      specific C4 deficiency. Firstly, we performed a population analysis in order to
      identify a statistically significant association: HLA-B35 and C4BQ0 alleles, in
      the total group of hypocomplementemic individuals, seem to be associated with the
      primary disease. Secondly, we defined HLA haplotypes clear-cut segregation in the
      hypocomplementemic families and we identified the most common HLA haplotypes
      carrying B35 and C4 null allele associated with this condition. With the aid of
      correspondence analysis and the Transmission Disequilibrium Test (TDT), we
      measured the strength of this association. In this work, mainly through family
      analysis, we envisaged a potentially interesting genomic trait, within HLA, close
      to B locus, that seems to be involved in hypocomplementemia itself and perhaps in
      hypocomplementemia-related disorders.

PMID- 15461866
TI  - Comparison between flurbiprofen and its nitric oxide-releasing derivatives HCT
      1026 and NCX-2216 on Abeta(1-42)-induced brain inflammation and neuronal damage
      in the rat.
AB  - Brain inflammation is an underlying factor in the pathogenesis of Alzheimers
      disease (AD). We investigated, in vivo, whether differences exist in the anti
      inflammatory and neuroprotective actions of flurbiprofen and its two nitric oxide
      donor derivatives, HCT-1026 and NCX-2216, and the ability of these two
      derivatives to release nitric oxide in the brain. In adult rats injected into the
      nucleus basalis with preaggregated Abeta(1-42) we investigated glia reaction, the
      induction of inducible nitric oxide synthase (iNOS), the activation of p38
      mitogen-activated protein kinase (p38MAPK) pathway and the number of choline
      acetyltransferase (ChAT)-positive neurons and, in naive rats we investigated, by
      microdialysis, cortical extracellular levels of nitrite. Injection of Abeta(1-42)
      induced iNOS and activation of p38MAPK 7 days after injection and an intense
      microglia and astrocyte reaction along with a marked reduction in the number ChAT
      positive neurons, persisting up to at least 21 days. Flurbiprofen, HCT-1026 and
      NCX-2216 (15 mg/kg) significantly attenuated the Abeta(1-42)-induced glia
      reaction, iNOS induction and p38MAPK activation 7 days after treatment and
      astrocytes reaction 21 days after treatment. On an equimolar basis, HCT-1026
      resulted the most active agent in reducing the Abeta(1-42)-induced microglia
      reaction. The cholinergic cell loss was also significantly reduced by 21 days of
      HCT-1026 treatment. No differences in body weight were found between the animals
      treated for 21 days with 15 mg/kg of either HCT-1026 or NCX-2216 and the
      controls. Oral administration of HCT-1026 (15 mg/kg) or NCX-2216 (100 mg/kg) to
      naive rats was followed by significant and long lasting increases in cortical
      nitrite levels. These findings indicate that the addition of a nitric oxide donor
      potentiates the anti-inflammatory activity of flurbiprofen in a model of brain
      inflammation.

PMID- 15461867
TI  - Omeprazole induces apoptosis in jurkat cells.
AB  - We report for the first time a potent apoptotic effect of omeprazole (OM).
      Apoptosis was induced in Jurkat cells in a time and concentration-dependent mode.
      Caspase 3 and PARP were rapidly cleaved in response to OM, but apoptosis was only
      partially inhibited by the caspase 3 inhibitor DEVD-CHO. OM also induced an early
      lysosomal destabilization which increased progressively and was correlated with a
      parallel increase in apoptotic cells. The cysteine protease inhibitor E64d gave
      strong protection against apoptosis thus proving the involvement of lysosomal
      enzymes in OM-induced apoptosis whereas, it did not impede the caspase 3
      cleavage. Instead ZVAD-fmk, a general caspase inhibitor, also able to inhibit
      cathepsin activity, protected cells completely from OM-induced apoptosis. It
      therefore seems that both caspases and cysteine cathepsins are involved in the
      execution stage of OM-induced apoptosis.

PMID- 15461868
TI  - Dendritic cells pulsed with peptides of gp63 induce differential protection
      against experimental cutaneous leishmaniasis.
AB  - The need for a vaccine against Leishmania spp., a major cause of worldwide
      morbidity and mortality, is urgent. We tested the efficacy of an experimental
      vaccination in murine models of cutaneous leishmaniasis, using dendritic cells
      (DCs) pulsed with synthetic or native parasite antigens. DCs pulsed with peptide
      154-169aa of gp63 or soluble promastigote lysate (SPL) triggered antigen-specific
      immune responses and efficiently reduced lesion formation and parasite load of
      genetically susceptible BALB/c mice infected with Leishmania major. This effect
      was accompanied by a modulation of the cellular immune response towards a Th1
      profile. Vaccination of genetically resistant CBA mice with DCs pulsed with
      peptide 154-169aa or SPL did not affect the course of the disease, whereas
      pulsing with the epitope 467-482aa of gp63 resulted in disease exacerbation,
      accompanied by a switch to a Th2 profile. In view of our continuously growing
      knowledge about the immunobiology of DCs, these findings suggest that vaccination
      with DCs pulsed with defined peptides could be a strategy against infectious
      diseases. Peptide selection is a prerequisite as they can differentially regulate
      the type of immune response in susceptible or resistant hosts.

PMID- 15461869
TI  - AIT-082 and methylprednisolone singly, but not in combination, enhance functional
      and histological improvement after acute spinal cord injury in rats.
AB  - Extracellular non-adenine based purines are neuroprotective. Preliminary studies
      indicate that administration of the synthetic purine 4-[[3-(1,6 dihydro-6-oxo-9
      purine-9-yl)-1-oxypropyl] amino] benzoic acid (AIT-082, leteprinim potassium) to
      rats immediately after acute spinal cord injury (SCI), improves functional
      outcome. The effects of potential new agents are often compared to
      methylprednisolone (MPSS). We evaluated the effects of AIT-082 and MPSS,
      separately and in combination, on the functional and morphological outcome of
      acute SCI in adult rats. After standardized T11-12 spinal cord compression rats
      were given intraperitoneally one of the following: vehicle (saline); MPSS (30
      mg/kg or 60 mg/kg body weight, first dose 15 min after crush); AIT-082 (60 mg/kg
      body weight daily, first dose 15 min after crush); or AIT-082 plus MPSS. After 1,
      3, or 21 days, the rats were perfused for histological analysis. AIT-082
      administrations significantly reduced locomotor impairment from 121 days post
      operatively. At 1 and 3 days post injury, AIT-082-treatment reduced tissue
      swelling, tissue loss and astrogliosis at the injured cords but did not alter the
      extent of hemorrhage and the number of macrophages and/or microglia. MPSS reduced
      hemorrhage and the number of macrophages and/or microglia, but did not alter
      astrogliosis. At 21 days, either AIT-082 or MPSS administration improved function
      and morphology similarly (less tissue loss and astrogliosis). In contrast,
      administration of AIT-082 and MPSS together abolished the beneficial effects
      observed when either drug was given individually. These results suggest that MPSS
      and AIT-082 may exert their beneficial effects through different and potentially
      antagonistic pathways.

PMID- 15461870
TI  - Ultradian variation of nerve growth factor plasma levels in healthy and
      schizophrenic subjects.
AB  - Some studies in animal models showed that several neurotrophins may be implicated
      in the regulation of light-dependent suprachiasmatic pacemaker and in other
      functions implicated in long-term memory acquisition during sleep. However, no
      data are known about the role played by NGF in ultradian regulation in humans.
      The aim of this study was to investigate whether or not there is a natural
      diurnal fluctuation during daytime in healthy and schizophrenic subjects with a
      normal light/dark cycle. In a sample of 33 subjects (10 male schizophrenics and
      23 healthy subjects) an ELISA assay was used to study the ultradian NGF cycle in
      blood samples at 9.00, 13.00 and 20.00 hours. The study showed an ultradian
      rhythm of NGF in healthy subjects with a "V" trend: higher at 9:00 and 20:00 and
      lower at 13:00. We also show significant differences between male and female
      controls. No NGF ultradian rhythm among schizophrenic patients compared to
      healthy subjects was found. The results of this study lead to a rhythmic NGF
      regulation that appears altered in schizophrenics, where higher levels in the
      morning and lower levels in the evening were observed, compared to the controls,
      and support the hypothesis of a role played by NGF in schizophrenia.

PMID- 15461871
TI  - Infliximab monotherapy for refractory psoriasis: preliminary results.
AB  - Tumour necrosis factor (TNF)-alpha plays an important role in the pathogenesis of
      psoriasis. Infliximab is an anti-TNF-alpha chimeric monoclonal antibody, which is
      licensed for the treatment of rheumatoid arthritis and Crohn's disease. Some
      reports have shown the efficacy of infliximab, either in monotherapy or in
      combination with methotrexate, for the treatment of psoriatic arthropathy and
      psoriasis. The efficacy and tolerability of infliximab monotherapy was evaluated
      in 29 patients with moderate to severe psoriasis, unresponsive to conventional
      treatments. Fourteen patients suffered from concomitant arthropathy. Patients
      received intravenous infliximab, 5mg/kg, at weeks 0, 2, and 6. After this 3-dose
      induction regimen, patients were followed-up at monthly intervals and retreated
      with a single-dose infusion in case of relapse of signs and symptoms. Clinical
      assessment was performed using the psoriasis area and severity index (PASI) to
      monitor psoriasis activity; pruritus and joint pain were assessed on a scale of 0
      to 3. A marked improvement of skin lesions and subjective symptoms was noted in
      the majority of patients; an excellent reduction of PASI score (> or =75%) was
      observed in 13.8% of cases at week 2, 71.4% at week 6 and 78.6% at week 10.
      During the follow-up period, some patients maintained satisfactory clinical
      results without requiring any additional infusions. In general, skin lesions
      showed a trend towards a more prolonged and sustained improvement as compared
      with subjective symptoms. Treatment was well tolerated and no serious adverse
      events occurred.

PMID- 15461872
TI  - Novel evidence of PLC delta2 involvement in the regulation of the differential
      evolution of human aneurysms.
AB  - The biological and molecular mechanisms which are responsible for the formation
      and possible evolution of human aneurysms are unknown. Previous investigations
      have pointed to the possible involvement of inositol specific-phospholipase C
      (PLC) in the mechanisms related to the formation or evolution of intracranial
      aneurysms, but, thus far, a relationship of one or more PLC isoforms with the
      biological signals influencing the fate of this lesion has not been demonstrated.
      The aim of this study was to investigate the expression, activity and possible
      modification of PLC isoforms in intracranial aneurysms in patients undergoing
      elective surgical repair after casual identification of unruptured aneurysms, or
      during emergency surgical repair of ruptured aneurysms. PLC and proliferating
      cell nuclear antigen (PCNA) expressions were detected by immunohistochemical
      analysis; PLC activity was obtained by measuring its hydrolytic activity on
      labelled PIP(2); PKC activity was measured by total kinase activity assay.
      Results indicated no substantial differences between controls and aneurysms, with
      the only exception being PLC delta2 which was nearly absent in controls and
      ruptured aneurysms, while strongly expressed and functionally active in almost
      all unruptured aneurysms. In addition, its expression always correlated with the
      proliferation cell marker PCNA, while its specific activity always correlated to
      PKC activity. PLC delta2 distribution, regulation and role in human tissues are
      still unknown Therefore, although preliminary, these data provide a novel insight
      into the signalling machinery influencing the aneurismal progression.

PMID- 15461873
TI  - Influence of cigarette smoking on vitamin E, vitamin A, beta-carotene and
      lycopene concentrations in human pre-ovulatory follicular fluid.
AB  - Increasing evidence suggests that fat soluble vitamins and micronutrients have
      the potential for local modulation of follicular development. Cigarette smoking
      has been associated with accelerated follicular depletion and derangement of
      reproductive functions. The present study was initiated to investigate the impact
      of cigarette smoking on follicular and plasma concentrations of vitamin A,
      vitamin E, lycopene and beta-carotene. Samples were collected from 17 smokers and
      43 non-smoking women undergoing assisted reproduction techniques. Assays were
      carried out by a reverse-phase high-pressure liquid chromatography (HPLC) method.
      Smokers had significantly (P < 0.05) lower levels of follicular fluid beta
      carotene in comparison to non-smokers (0.02 +/- 0.02 vs. 0.09 +/- 0.02,
      respectively). No other significant influences on follicular and plasma
      concentrations were noted. Smokers showed a significantly (P < 0.05) lower
      fertilization rate in comparison to non-smokers, (55.9 % vs. 71.5 % ,
      respectively). It is postulated that follicular depletion of the antioxidant beta
      carotene occurs in response to oxidative stress imposed by cigarette smoke.

PMID- 15461874
TI  - Association of myasthenia gravis and antisynthetase syndrome: a case report.
AB  - Myasthenia gravis is a chronic disease of neuromuscular transmission caused by
      loss of acetylcholine receptors. It can be found in association with other
      autoimmune disorders. We report the case of a 47-yr-old woman affected by
      Myasthenia gravis who complained of fever, progressive weakness of proximal limb
      muscle, arthritis and Raynauds phenomenon and dyspnea. Chest X-rays and CT scan
      showed an interstitial lung disease; laboratory data indicated an inflammatory
      picture and increased serum muscle enzymes. Evaluation for infectious, metabolic,
      iatrogenic and neoplastic aetiologies was unrevealing. The patients clinical
      condition together with positive results on antisynthetase antibody assay lead to
      the diagnosis of antisynthetase syndrome. To our knowledge, this is the first
      report on the association of Myasthenia gravis with antisynthetase syndrome.

PMID- 15461875
TI  - Association of cyclosporine and 311 nM UVB in the treatment of moderate to severe
      forms of psoriasis: a new strategic approach.
AB  - Psoriasis is a T-lymphocyte mediated autoimmune disease. The response to
      therapies targeting T-lymphocytes suggest that the latter is a key cell in the
      pathogenesis of the disease. Cyclosporine (CsA) inhibits the proliferation and
      the IL-2 dependent expansion of T-lymphocytes. Ultraviolet radiation is an
      effective treatment for psoriasis. Several studies have demonstrated a
      significant improvement of the therapeutic response when narrow-band radiation is
      issued by TL-01 fluorescent lamp compared to broad- band UVB issued by other
      fluorescent sources. The effects of UVB on the immune system appear to be limited
      to the cell-mediated compartment of the immune response. In order to reduce the
      cumulative dose of UVB and limit the toxicity of drugs in the therapy of
      psoriasis, phototherapy with UVB has been used as treatment in association with
      other standard therapies. The purpose of the study is to evaluate, in patients
      with moderate to severe psoriasis a combined therapy with Cyclosporine A and 311
      nm UVB phototherapy.

PMID- 15461876
TI  - Clinical effectiveness and cost-effectiveness of clopidogrel and modified-release
      dipyridamole in the secondary prevention of occlusive vascular events: a
      systematic review and economic evaluation.
AB  - OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of two
      alternative antiplatelet agents, clopidogrel and modified-release (MR)
      dipyridamole, relative to prophylactic doses of aspirin for the secondary
      prevention of occlusive vascular events. DATA SOURCES: Electronic databases.
      REVIEW METHODS: A total of 2906 titles and abstracts were rigorously screened and
      441 studies were assessed in detail. Two RCTs were identified. For the assessment
      of cost-effectiveness, eight reviews were identified. The results were presented
      in structured tables and as a narrative summary. No additional clinical
      effectiveness data were presented in either of two company submissions. All
      economic evaluations (including accompanying models) included in the company
      submissions were assessed. Following this analysis, if the existing models
      (company or published) were not sufficient, a de novo model or modified versions
      of the models were developed. RESULTS: In the CAPRIE trial the point estimate for
      the primary outcome, i.e. ischaemic stroke, myocardial infarction (MI) or
      vascular death, favoured clopidogrel over aspirin, but the boundaries of the
      confidence intervals raise the possibility that clopidogrel is not more
      beneficial than aspirin. In terms of the secondary outcomes reported, there was a
      non-significant trend in favour of clopidogrel over aspirin but the boundaries of
      the confidence intervals on the relative risks all crossed unity. There was no
      difference in the number of patients ever reporting any bleeding disorder in the
      clopidogrel group compared with the aspirin group. The incidences of rash and
      diarrhoea were statistically significantly higher in the clopidogrel group than
      the aspirin group. Patients in the aspirin group had a higher incidence of
      indigestion/nausea/vomiting than patients in the clopidogrel group.
      Haematological adverse events were rare in both the clopidogrel and aspirin
      groups. No cases of thrombotic thrombocytopenic purpura were reported in either
      group. Treatment with MR-dipyridamole alone did not significantly reduce the risk
      of any of the primary outcomes reported in ESPS-2 compared with treatment with
      aspirin. ASA-MR-dipyridamole was significantly more effective than aspirin alone
      in patients with stroke or transient ischaemic attacks (TIAs) at reducing the
      outcome of stroke and marginally more effective at reducing stroke and/or death.
      Treatment with ASA-MR-dipyridamole did not statistically significantly reduce the
      risk of death compared to treatment with aspirin. The number of strokes was
      statistically significantly reduced in the ASA-MR-dipyridamole group compared
      with the MR-dipyridamole group. In terms of the other primary outcomes, stroke
      and/or death and death, the results favoured treatment with ASA-MR-dipyridamole
      but the findings were not statistically significant. There was no difference in
      the number of bleeding complications between the ASA-MR-dipyridamole and aspirin
      groups. The incidence of bleeding complications was significantly lower in the MR
      dipyridamole treatment group. More patients in the MR-dipyridamole treatment
      groups experienced headaches compared to patients receiving treatment with
      aspirin alone. The York model assessed the cost-effectiveness of differing
      combinations of treatment strategies in four patient subgroups, under a number of
      different scenarios. The results of the model were sensitive to the assumptions
      made in the alternative scenarios, in particular the impact of therapy on non
      vascular deaths. CONCLUSIONS: Clopidogrel was marginally more effective than
      aspirin at reducing the risk of ischaemic stroke, MI or vascular death in
      patients with atherosclerotic vascular disease, however, it did not statistically
      significantly reduce the risk of vascular death or death from any cause compared
      with aspirin. There was no statistically significant difference in the number of
      bleeding complications experienced in the clopidogrel and aspirin groups. MR
      dipyridamole in combination with aspirin was superior to aspirin alone at
      reducing the risk of stroke and marginally more effective at reducing the risk of
      stroke and/or death. Compared with treatment with MR-dipyridamole alone, MR
      dipyridamole in combination with aspirin significantly reduced the risk of
      stroke. Treatment with MR-dipyridamole in combination with aspirin did not
      statistically significantly reduce the risk of death compared with aspirin.
      Compared with treatment with MR-dipyridamole alone, bleeding complications were
      statistically significantly higher in patients treated with aspirin and MR
      dipyridamole in combination with aspirin. Due to the assumptions that have to be
      made, no conclusions could be drawn about the relative effectiveness of MR
      dipyridamole, alone or in combination with aspirin, and clopidogrel from the
      adjusted indirect comparison. The following would apply for a cost of up to
      GBP20,000-40,000 per additional quality-adjusted life-year. For the stroke and
      TIA subgroups, ASA-MR-dipyridamole would be the most cost-effective therapy given
      a 2-year treatment duration as long as all patients were not left disabled by
      their initial (qualifying) stroke. For a lifetime treatment duration, ASA-MR
      dipyridamole would be considered more cost-effective than aspirin as long as
      treatment effects on non-vascular deaths are not considered and all patients were
      not left disabled by their initial stroke. In patients left disabled by their
      initial stroke, aspirin is the most cost-effective therapy. Clopidogrel and MR
      dipyridamole alone would not be considered cost-effective under any scenario. For
      the MI and peripheral arterial disease subgroups, clopidogrel would be considered
      cost-effective for a treatment duration of 2 years. For a lifetime treatment
      duration, clopidogrel would be considered more cost-effective than aspirin as
      long as treatment effects on non-vascular deaths are not considered. It is
      suggested that the combination of clopidogrel and aspirin should be evaluated for
      the secondary prevention of occlusive vascular events. Also randomised, direct
      comparisons of clopidogrel and MR-dipyridamole in combination with aspirin are
      required to inform the treatment of patients with a history of stroke and TIA,
      plus trials that compare treatment with clopidogrel and MR-dipyridamole for the
      secondary prevention of vascular events in patients who demonstrate a genuine
      intolerance to aspirin.

PMID- 15461877
TI  - Pegylated interferon alpha-2a and -2b in combination with ribavirin in the
      treatment of chronic hepatitis C: a systematic review and economic evaluation.
AB  - OBJECTIVES: To assess the clinical-effectiveness and cost-effectiveness of
      pegylated interferon-alpha combined with ribavirin in the treatment of chronic
      hepatitis C. DATA SOURCES: Electronic databases, reference lists of retrieved
      reports, and the industry submissions to the National Institute for Clinical
      Excellence. REVIEW METHODS: Sources were rigorously searched and studies were
      selected that met the inclusion criteria of being randomised controlled trials
      (RCTs) involving comparisons between pegylated interferon-alpha plus ribavirin
      and non-pegylated interferon plus ribavirin (two trials) or pegylated interferon
      alone and non-pegylated interferon alone (four trials). The primary outcome in
      all trials was sustained virological response (SVR) at follow-up. The trials were
      generally of good quality, although reporting of methodological details could
      have been more thorough in places. A cost-effectiveness model followed a
      hypothetical cohort of 1000 individuals with chronic hepatitis C over a 30-year
      period. RESULTS: In the two trials that tested pegylated interferon plus
      ribavirin against non-pegylated interferon plus ribavirin the combined percentage
      of sustained virological response was 55%. The relative risk (RR) for remaining
      infected was reduced by 17% for pegylated interferon plus ribavirin compared with
      non-pegylated interferon plus ribavirin. Response to therapy varied according to
      viral genotype. Patients with genotype 1 had the lowest levels of sustained
      virological response and patients with genotype 2 or 3 had the highest. In the
      four trials that evaluated pegylated interferon monotherapy against non-pegylated
      interferon the combined sustained virological response rates were 31% for
      pegylated interferon and 14% for non-pegylated interferon. The RR for remaining
      infected with hepatitis C was reduced by 20% with the use of pegylated
      interferon. Patients with genotype 1 had the lowest levels of sustained
      virological response. There were also variations in sustained virological
      response according to other prognostic variables such as baseline viral load.
      Regimens involving pegylated interferon appear to be fairly well tolerated.
      Adverse events were been reported, but they did not differ substantially from
      levels of adverse events in regimens involving non-pegylated interferon. The
      incremental discounted cost per QALY for comparing no active treatment to 48
      weeks of dual therapy with pegylated interferon and ribavirin (PEG + RBV) was
      6045 pounds sterling. When moving from 48 weeks of dual therapy with non
      pegylated interferon and ribavirin (IFN + RBV) to 48 weeks of dual therapy with
      PEG + RBV the figure was 12,123 pounds sterling. Subgroup analyses for dual PEG +
      RBV therapy demonstrated that the most favourable incremental discounted cost per
      QALY estimates were for patients infected with genotypes 2 and 3, and with low
      baseline viral load (3921 pounds sterling) compared with no active treatment.
      Results of one-way sensitivity analyses showed that the estimates varied
      according to differences in SVRs, drug costs and discount rates. In general
      estimates remained under 30,000 pounds sterling per QALY. The incremental
      discounted cost per QALY when moving from no active treatment to 48 weeks of
      monotherapy with pegylated interferon was 6484 pounds sterling. When moving from
      48 weeks of monotherapy with IFN to 48 weeks of monotherapy with PEG the figure
      was 8404 pounds sterling. As with dual therapy, the lowest incremental cost per
      QALY was for patients with genotypes 2 and 3 and low baseline viral load, in the
      range 2641-4194 pounds sterling. The highest estimates were for patients with
      genotype 1 and high baseline viral load, around 30,000 pounds sterling.
      CONCLUSIONS: Well-designed RCTs show that patients treated with pegylated
      interferon, both as dual therapy and as monotherapy, experience higher sustained
      viral response rates than those treated with non-pegylated interferon. Patients
      with genotypes 2 and 3 experience the highest response, with rates in excess of
      80%. Patients with the harder to treat genotype 1 nevertheless benefit, with up
      to 46% of patients experiencing an SVR in one of the trials. Pegylated interferon
      also appears to be relatively cost-effective in both monotherapy and dual
      therapy, with cost per QALY estimates remaining generally under 30,000 pounds
      sterling. The most favourable estimates were for patients with genotypes 2 and 3.
      Pegylated interferon is a relatively new intervention in the treatment of
      hepatitis C and therefore there are areas where further research is needed. These
      include: efficacies of therapy with PEG-alpha-2a vs PEG-alpha-2b; retreatment of
      previous non-responders using pegylated interferon; efficacy of treatments and
      long-term outcomes in patients who have other co-morbidities; prospective tests
      of rules governing stopping treatment; treating patients with acute hepatitis C;
      problems that may occur in a minority of patients with hepatitis C, such as
      cryoglobulinaemia and vasculitis; additional psychological effects on quality of
      life due to hepatitis C and also on the treatment of children and adolescents
      with hepatitis C.

PMID- 15461878
TI  - Clopidogrel used in combination with aspirin compared with aspirin alone in the
      treatment of non-ST-segment-elevation acute coronary syndromes: a systematic
      review and economic evaluation.
AB  - OBJECTIVES: To review systematically the clinical effectiveness and the cost
      effectiveness of clopidogrel used in combination with standard therapy including
      aspirin, compared with standard therapy alone for the treatment of non-ST-segment
      elevation acute coronary syndromes (ACS). DATA SOURCES: Electronic databases.
      Manufacturers' submissions. REVIEW METHODS: Studies were selected using rigorous
      criteria. The quality of randomised controlled trials (RCTs) was assessed
      according to criteria based on NHS CRD Report No. 4, and the quality of
      systematic reviews was assessed according to the guidelines for the Database of
      Reviews of Effect (DARE) criteria. The quality of economic evaluations was
      assessed according to a specifically tailored checklist. The clinical
      effectiveness and cost-effectiveness of clopidogrel in combination with standard
      therapy compared with standard therapy alone were synthesised through a narrative
      review with full tabulation of the results of the included studies. In the
      economic evaluations, a cost-effectiveness model was constructed using the best
      available evidence to determine cost-effectiveness in a UK setting. RESULTS: One
      RCT (the CURE trial) was a randomised, double-blind, placebo-controlled trial of
      high quality and showed that clopidogrel in addition to aspirin was significantly
      more effective than placebo plus aspirin in patients with non-ST-segment
      elevation ACS for the composite outcome of death from cardiovascular causes, non
      fatal myocardial infarction or stroke over the 9-month treatment period. However,
      clopidogrel was associated with a significantly higher number of episodes of both
      major and minor bleeding. The results from the five systematic reviews that
      assessed the adverse events associated with long-term aspirin use showed that
      aspirin was associated with a significantly higher incidence of haemorrhagic
      stroke, extracranial haemorrhage and gastrointestinal haemorrhage compared with
      placebo. Of the cost-effectiveness evidence reviewed, only the manufacturer's
      submission was considered relevant from the perspective of the NHS. The review of
      this evidence highlighted potential limitations within the submission in its use
      of data and in the model structure used. These limitations led to the development
      of a new model with the aim of providing a more reliable estimate of the cost
      effectiveness from the perspective of the UK NHS. This model indicated that
      clopidogrel appears cost-effective compared with standard care alone in patients
      with non-ST-elevation ACS as long as the NHS is willing to pay GBP6078 per
      quality of life year (QALY). The results were most sensitive to the inclusion of
      additional strategies that assessed alternative treatment durations with
      clopidogrel. Although treatment with clopidogrel for 12 months remained cost
      effective for the overall cohort, provisional findings indicate that the shorter
      treatment durations may be more cost-effective in patients at low risk.
      CONCLUSIONS: The results of the CURE trial indicate that clopidogrel in
      combination with aspirin was significantly more effective than placebo combined
      with aspirin in a wide range of patients with ACS. This benefit was largely
      related to a reduction in Q-wave myocardial infarction. There was no
      statistically significant benefit in relation to mortality. The trial data
      suggested that a substantial part of the benefit derived from clopidogrel is
      achieved by 3 months, with a further small benefit over the remaining 9 months of
      chronic treatment. The results from the base-case model suggest that treatment
      with clopidogrel as an adjunct to standard therapy (including aspirin) for 12
      months, compared with standard therapy alone, is cost-effective in non-ST
      elevation ACS patients as long as the health service is willing to pay GBP6078
      per additional QALY. However, although treatment with clopidogrel for 12 months
      remained cost-effective for the overall cohort, provisional findings indicate
      that the shorter treatment durations may be more cost-effective in patients at
      low risk. To estimate the exact length of time that clopidogrel in addition to
      standard therapy should be prescribed for patients with non-ST-segment ACS would
      require a prospective trial that randomised patients to various durations of
      therapy. This would accurately assess whether a 'rebound' phenomenon occurs in
      patients if clopidogrel were stopped after 3 months of treatment.

PMID- 15461879
TI  - Provision, uptake and cost of cardiac rehabilitation programmes: improving
      services to under-represented groups.
AB  - OBJECTIVES: To estimate UK need for outpatient cardiac rehabilitation, current
      provision and identification of patient groups not receiving services. To conduct
      a systematic review of literature on methods to improve uptake and adherence to
      cardiac rehabilitation. To estimate cost implications of increasing uptake of
      cardiac rehabilitation. DATA SOURCES: Hospital Episode Statistics (England).
      Hospital Inpatient Systems (Northern Ireland). Patients Episode Database for
      Wales. British Association for Cardiac Rehabilitation/British Heart Foundation
      surveys. Cardiac rehabilitation centres. Patients from general hospitals.
      Electronic databases. REVIEW METHODS: The study analysed hospital discharge
      statistics to ascertain the population need for outpatient cardiac rehabilitation
      in the UK. Surveys of cardiac rehabilitation programmes were conducted to
      determine UK provision, uptake and audit activity, and to identify local
      interventions to improve uptake. Data were also examined from a trial estimating
      eligibility for cardiac rehabilitation and non-attendance. A systematic review of
      interventions to improve patient uptake, adherence and professional compliance in
      cardiac rehabilitation was conducted. Estimated costs of improving uptake were
      identified from national survey, systematic review and sampled cardiac
      rehabilitation programmes. RESULTS: In England, Wales and Northern Ireland nearly
      146,000 patients discharged from hospital with primary diagnosis of acute
      myocardial infarction, unstable angina or following revascularisation were
      potentially eligible for cardiac rehabilitation. In England in 2000, 45-67% of
      these patients were referred, with 27-41% attending outpatient cardiac
      rehabilitation. If all discharge diagnoses of ischaemic heart disease were
      considered, nearly 299,000 patients would be potentially eligible and in England
      rates of attendance and referral would be 22-33% and 13-20% respectively. Rates
      of referral and attendance were similar in Wales, but somewhat lower in Northern
      Ireland. It was found that referral and attendance of older people and women at
      cardiac rehabilitation tended to be low. It was also suggested that patients from
      ethnic minorities and those with angina or heart failure were less likely to be
      referred to or join programmes. A wide range of local interventions suggested
      awareness of the problem of uptake. In an NHS-funded randomised controlled trial,
      possibly representing more optimal protocol-led care, medical and nursing staff
      identified 73-81% of patients with acute myocardial infarction as eligible for
      cardiac rehabilitation. Excluded patients tended to be older with more severe
      presentation of cardiac disease. Experiences of patients suggested that uptake
      may be improved by addressing issues of motivation and relevance of
      rehabilitation to future well-being, co-morbidities, site and time of programme,
      transport and care for dependents. Systematic review of studies supported the use
      of letters, pamphlets or home visits to motivate patients and the use of trained
      lay visitors. Self-management techniques showed some value in promoting adherence
      to lifestyle changes. Studies examining professional compliance found that
      professional support for practice nurses may have value in the coordination of
      postdischarge care. Average costs in 2001 of cardiac rehabilitation to the health
      service per patient completing a cardiac rehabilitation programme were about
      GBP350 (staff only) and GBP490 (total). If services were modelled on an
      intermediate multidisciplinary configuration with three to five key staff,
      approximately 13% more patients could be treated with the same budget. Depending
      on staffing configuration an approximate 200-790% budget increase would be
      required to provide cardiac rehabilitation to all potentially eligible patients.
      CONCLUSIONS: Provision of outpatient cardiac rehabilitation in the UK is low and
      little is known about the capacity of cardiac rehabilitation centres to increase
      this provision. There is an uncoordinated approach to audit data collection and
      few interventions aimed at improving the situation have been formally evaluated.
      Motivational communications and trained lay volunteers may improve uptake of
      cardiac rehabilitation, as may self-management techniques. Experience of low-cost
      interventions and good practice exists within rehabilitation centres, although
      cost information frequently is not reported. Increased provision of outpatient
      cardiac rehabilitation will require extra resources. Further trials are required
      to compare the cost-effectiveness of comprehensive multidisciplinary
      rehabilitation with simpler outpatient programmes, also research is needed into
      economic and patient preference studies of the effects of different methods of
      using increased funding for cardiac rehabilitation. An evaluation of a range of
      interventions to promote attendance in all patients and under-represented groups
      would also be useful. The development of standards is suggested for audit methods
      and for eligibility criteria, as well as regular and comprehensive data
      collection to estimate the need for and provision of cardiac rehabilitation.
      Further areas for intervention could be identified through qualitative studies,
      and the extension of low-cost interventions and good practice within
      rehabilitation centres. Regularly updated systematic reviews of relevant
      literature would also be useful.

PMID- 15461880
TI  - Bats in the Belfry or Bugs in the Brain: Is Mental Illness an Infection?

PMID- 15461881
TI  - Zoonoses.

PMID- 15461882
TI  - Herd Immunity from Meningococcal Serogroup C Conjugate Vaccination.

PMID- 15461883
TI  - Trends in Sepsis-related Neonatal Mortality.

PMID- 15461884
TI  - Decline in Invasive Pneumococcal Disease after Use of Protein-polysaccharide
      Conjugate Vaccine.

PMID- 15461885
TI  - Advances in Sepsis Treatment.
AB  - Investigations of novel sepsis treatments have proven ineffective in the past.
      Despite advances in overall care of critically ill patients, therapies
      specifically designated for sepsis were lacking. However, research unveiled a
      complex interaction between the coagulation and inflammation systems, which has
      served as an impetus for innovative pharmacologic therapies in the treatment of
      patients with sepsis. This article summarizes the results of trials involving
      drotrecogin alfa (activated), or recombinant human activated protein C, the only
      medicine currently approved by the US Food and Drug Administration for the
      treatment of severe sepsis. In addition, the beneficial effects of early, goal
      directed resuscitation, guided by continuous central venous oxygen saturations,
      are discussed, with the issues involved in the use of corticosteroids in a subset
      of patients with septic shock. This article also reviews the beneficial effects
      of tight glycemic control in postoperative critically ill patients and considers
      whether the data can be extrapolated to medical patients.

PMID- 15461886
TI  - Toll-like Receptors and Sepsis.
AB  - Recent evidence suggests that Toll-like receptors (TLRs) play a major role in
      innate immunity to recognize specific molecular patterns derived from pathogens,
      including lipid, protein, DNA, and RNA, and to fight against pathogens. Each TLR
      displays a difference in the expression pattern, intracellular localization, and
      signaling pathway, resulting in the distinct immune responses. The resultant
      immune activation augments host resistance to a variety of infectious organisms.
      However, such responses may exceed the threshold to maintain host homeostasis in
      the case of sepsis. TLR-mediated innate immune activation also induces several
      molecules shown to negatively regulate TLR signaling. Thus, TLRs may play an
      important role in positive and negative regulation of immune responses during
      sepsis.

PMID- 15461888
TI  - Foot Infections in Diabetic Patients.

PMID- 15461887
TI  - Genetic Susceptibility to Sepsis: A Possible Role for Mannose-binding Lectin.
AB  - Sepsis is an increasing problem in modern medicine and the leading cause of death
      in noncoronary intensive care unit patients. Over the past few years, several
      studies have provided data indicating that relatively common polymorphisms in
      genes encoding proteins of importance for innate immune recognition, the
      inflammatory response, and for coagulation and fibrinolysis, are associated with
      susceptibility for and outcome of sepsis. Recently, several studies have shed
      light on the importance of deficiency of mannose-binding lectin (MBL) as a
      susceptibility factor for sepsis. This review summarizes the evidence that
      critically ill patients carrying MBL-variant alleles may be at increased risk for
      severe sepsis. The prospect for the future is that genetic profiling may guide in
      identifying critically ill patients at increased risk for sepsis and poor
      outcome, and in tailoring a more individual and effective therapy.

PMID- 15461889
TI  - Bacterial and Lyme Arthritis.
AB  - Septic arthritis is an infectious disease emergency, requiring aggressive joint
      drainage and prompt antibiotic therapy. Because age and joint damage are major
      risk factors, septic arthritis may become more common as the baby-boom generation
      reaches senescence. Bacteremic joint infections have a high mortality, and long
      term disability from joint damage is common. Lyme arthritis has a negligible
      mortality and low morbidity but causes disproportionate popular anxiety. Most
      patients with Lyme arthritis respond well to oral antibiotic regimens and recover
      completely. A few patients develop antibiotic-resistant Lyme arthritis, which is
      probably autoimmune in nature and responds to immunosuppressive therapy. This
      paper reviews the presentation, diagnosis, and management of bacterial and Lyme
      arthritis. Septic arthritis caused by Streptococcus pneumoniae and group B
      streptococci may be increasing in prevalence. Prospective studies are required to
      determine whether there is any benefit of surgical or arthroscopic joint drainage
      in septic arthritis, compared with serial arthrocentesis, and to determine the
      role of corticosteroid therapy in septic arthritis in adults, if any.

PMID- 15461890
TI  - Infections Associated with Prosthetic Knee and Prosthetic Hip.
AB  - Arthroplasty of the knee and hip is a common procedure. There is a risk of
      infection with primary arthroplasty, with an incidence of 1% to 2%. Significant
      cost and morbidity are associated with infection of the prosthetic joint. Most
      infections (60% to 70%) are caused by staphylococci, but approximately 10% are
      caused by streptococci and/or enterococci, whereas the remainder are caused by
      gram-negative enteric aerobes or anaerobic flora. Surgical revision is often
      required for cure because the biofilm that adheres to the infected prosthesis
      precludes antibiotic therapy from being effective. Biofilm formation occurs
      consistently as a consequence of host protein deposition on the prostheses, which
      serve as ligands for bacterial receptors. Once established, biofilm infections
      require removal of the prosthesis in order to effect a cure. Clinical and
      radiologic features are not specific for the diagnosis. Culture is specific but
      not sensitive enough to establish a pathogen in all cases. Surgical approaches
      are varied and range from debridement with retention of the prostheses to
      amputation of the limb. The most favored approach is the two-stage delayed
      reimplantation, in which patients receive specific antibiotic therapy for 6 weeks
      or more. Several additional antibiotics other than vancomycin are available for
      methicillin-resistant staphylococcal infection, but these are still unproven in
      the treatment of osteomyelitis or prosthetic joint infection.

PMID- 15461891
TI  - Bacterial Pyomyositis.
AB  - Bacterial pyomyositis has been defined as a subacute, deep bacterial infection of
      the soft tissues. The entity was originally described only in tropical climates,
      but it is increasing in incidence in temperate climates, such as in the United
      States. This is mainly attributed to the presence of immunocompromising states
      such as HIV/AIDS or liver disease. The etiology of pyomyositis remains a mystery,
      but its characteristics are well-described. If untreated, the disease process
      progresses through three distinct stages. The first stage is defined by vague
      complaints, muscle pain, and a low-grade fever. The second stage presents as
      worsening pain, swelling, fever, and actual abscess formation in the muscle. If
      the patient remains untreated, pyomyositis progresses to the third stage, which
      includes septicemia and possible septic shock. Large muscles around the pelvis
      are most commonly affected, and Staphylococcus aureus is the bacteria seen in
      most documented cases. To make a timely diagnosis and prevent serious sequelae,
      physical examination, laboratory results, imaging studies, and a high clinical
      suspicion must all be combined. Magnetic resonance imaging is the diagnostic
      study of choice, but it may be inconclusive early in the disease process.
      Definitive diagnosis must be made with aspiration or surgical drainage. Once
      diagnosed, treatment consists of appropriate intravenous antibiotics and possible
      surgical intervention. A full recovery is expected if appropriate treatment is
      initiated early in the process.

PMID- 15461892
TI  - International Travel: Recommendations for the HIV-infected Patient.
AB  - In order to prevent travel-related diseases in patients infected with HIV,
      pretravel planning that includes vaccination, chemoprophylaxis, and behavioral
      modification is recommended. Many HIV-infected individuals successfully treated
      with highly active antiretroviral therapy may travel safely. However, patients
      with reduced CD4 lymphocyte counts are at increased risk for bacterial,
      mycobacterial, viral, fungal, and parasitic infections. Recommendations for
      vaccination and chemoprophylaxis are based on immune status and risk of
      infection. The efficacy of vaccination is dependant on CD4 lymphocyte count;
      inactivated and polysaccharide vaccines are considered safe in this population.
      Behavioral modifications to prevent food- and waterborne disease are an important
      component of disease prevention. A travel-health practitioner should review
      travel duration, destination, and activities, and assess the risk-benefit ratio
      of vaccination and chemoprophylaxis, in order to reduce the likelihood of travel
      associated illness.

PMID- 15461893
TI  - The HIV Epidemic Among Individuals with Mental Illness in the United States.
AB  - People with depression and other mental illness comprise a growing proportion of
      individuals living with HIV in the United States; at the same time, the
      prevalence of HIV among mentally ill individuals is at least seven times higher
      than in the general population. Individuals with mental illness are particularly
      vulnerable to infection with HIV because of several factors, including the higher
      prevalence of poverty, homelessness, high-risk sexual activities, drug abuse,
      sexual abuse, and social marginalization found in this population. Nevertheless,
      mentally ill individuals are often not screened for HIV and may not be
      appropriately targeted in current HIV prevention efforts. Moreover, despite
      widespread access to antiretroviral treatment in the United States, HIV outcomes
      among mentally ill individuals continue to be poor. This disparity can be
      explained by several interrelated factors, including lower rates of highly active
      antiretroviral therapy (HAART) utilization, lower rates of adherence to HAART,
      and immunologic changes associated with mental illness itself. We need to improve
      our design of prevention, screening, and treatment programs to better reach
      individuals with comorbid HIV and mental illness.

PMID- 15461894
TI  - Diabetes and obesity: medical diseases, surgical cure?

PMID- 15461896
TI  - Combination therapy of dyslipidemia in non-insulin-dependent diabetes mellitus
      and the metabolic syndrome.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) and the metabolic syndrome
      separately and additively increase the risk for atherosclerotic cardiovascular
      disease. Considering the high cardiovascular risk associated with NIDDM and the
      metabolic syndrome, aggressive therapy of dyslipidemia with tailored combination
      therapy should be considered given informed consent and discussion of risks. In
      addition to statins, niacin, and fibrates, therapies shown to decrease the risk
      for atherosclerotic cardiovascular disease include omega-3 fatty acids, diet,
      exercise, and optimal blood pressure control with thiazides and blockers of the
      renin-angiotensin system. These therapies should also be considered to reduce the
      high cardiovascular risk associated with NIDDM and the metabolic syndrome.

PMID- 15461897
TI  - Waiting to inhale: noninjectable insulin, are we there yet?
AB  - Subcutaneous injection has been the only route of insulin administration for
      patients with type 1 or type 2 diabetes for the past 80 years. Although research
      and development in this time has improved the insulin treatments themselves, it
      is only now that alternative routes of insulin administration are becoming
      viable. Many avenues of insulin administration have been explored, including
      oral, buccal, and pulmonary routes. However, these methods of noninvasive insulin
      delivery are not free from difficulties and only preliminary data are available
      for oral insulin pills and buccal insulin sprays. The most promising alternative
      route of delivery appears to be inhaled insulin and two devices are already in
      phase III testing. Nevertheless, inhaled insulin devices will still have to
      overcome some problems and recent studies show that these challenges are
      currently being confronted. It appears that years of research into noninvasive
      methods of insulin administration are close to fruition and this review outlines
      the most recent findings in this area.

PMID- 15461898
TI  - Basal insulin therapy.
AB  - The initiation of insulin therapy is a significant event for patients with
      diabetes and the physicians who care for them. Reluctance to begin insulin is
      multifactorial, with a major stumbling block being the perceived complexity of
      insulin. However, this complexity can be easily overcome by separation of insulin
      administration into its two components: basal and bolus therapy. An understanding
      of the role of basal insulin in the regulation of glucose and the development of
      strategies to implement basal insulin therapy can provide a transition that is
      rational and highly effective in most patients. The strategy also offers a unique
      approach to diabetes education, which permits a focused and patient-specific
      correction to glucose abnormalities.

PMID- 15461899
TI  - Inpatient management of hospitalized patients with type 2 diabetes.
AB  - Over the past 4 years, the scientific literature addressing issues relevant to
      inpatient hyperglycemia and its management has grown dramatically but remains
      incomplete. The growing interest in inpatient diabetes management is particularly
      pertinent given the epidemic rise in the prevalence of type 2 diabetes and the
      associated increase in the proportion of inpatients carrying this diagnosis. The
      benefits of aggressive glucose control are well-established in certain admission
      categories. These benefits likely apply to many other admission diagnoses, but
      remain unproven at this time. Similarly, the best methods of glucose control
      remain uncertain in the various inpatient settings. Intensive insulin infusion
      therapy is becoming the standard care in the intensive care unit setting. Its use
      is also growing in less acute inpatient settings but requires further study.
      Inpatient subcutaneous insulin recommendations are general based on experience
      gained in the outpatient setting but offer a practical, physiologic approach.

PMID- 15461900
TI  - The use of bolus insulin and advancing insulin therapy in type 2 diabetes.
AB  - Attention to meal-related insulin replacement in type 2 diabetes is important as
      insulin deficiency progresses. The physiology in type 2 and type 1 diabetes
      differs, and optimal use of basal-bolus therapy in type 2 diabetes requires
      attention to such issues as the role for oral medications, residual endogenous
      insulin, and differing meal patterns in older and more obese individuals.

PMID- 15461901
TI  - Is weight loss the best lifestyle intervention for type 2 diabetes?

PMID- 15461902
TI  - Women, type 2 diabetes, and fracture risk.
AB  - Older women with type 2 diabetes have an increased risk of nonspine fractures.
      The higher risk of falling associated with diabetes partially accounts for this
      increased risk. Current evidence suggests that there may also be impairments of
      bone strength in type 2 diabetes that are not well captured by bone mineral
      density testing. There is limited observational evidence that poor glycemic
      control and the associated complications of peripheral neuropathy and retinopathy
      may increase fractures, falls, and bone loss. However, this hypothesis has not
      been tested in a randomized trial. It remains to be elucidated whether treating
      diabetes and diabetic complications aggressively can alter skeletal health either
      directly or by preventing diabetic complications that contribute to falls and
      fractures. Health care professionals should be aware of the increased fracture
      risk among older women with diabetes and should ensure screening, treatment, and
      fall prevention strategies are appropriately implemented.

PMID- 15461903
TI  - Lactation, diabetes, and nutrition recommendations.
AB  - Human milk is recommended for infants throughout at least the first year of life.
      Breastfeeding is also recommended for infants of women with preexisting diabetes
      or gestational diabetes. Dietary Reference Intakes (DRIs) 2002 provides
      recommendations for energy and macronutrients for all ages and for pregnancy and
      lactation. During the first 6 months, infants receive an average of 500 kcal/d
      from human milk, and during the second 6 months 400 kcal/d. To cover this need
      for the first 6 months of lactation, women need an additional energy intake of
      330 kcal/d plus the approximately 170 kcal/d that is supplied by the women's
      tissue stores, and for the second 6 months 400 kcal/d. The DRIs also set
      recommended levels for both the infant and mother for carbohydrate, protein, and
      fats. Women with type 1 diabetes may have problems initiating breastfeeding, and
      with hypo- and hyperglycemia during lactation. Breastfeeding may have long-term
      beneficial effects on glycemia in women with gestational diabetes. More research
      is needed on all aspects of lactation in women with diabetes.

PMID- 15461904
TI  - Gestational diabetes and nutritional recommendations.
AB  - The goals of medical nutrition therapy for gestational diabetes mellitus (GDM)
      are to meet the maternal and fetal nutritional needs, as well as to achieve and
      maintain optimal glycemic control. Nutrition requirements during pregnancy are
      similar for women with and without GDM. The American Diabetes Association and the
      American College of Obstetrics and Gynecology recommend nutrition therapy for GDM
      that emphasizes food choices to promote appropriate weight gain and normoglycemia
      without ketonuria, and moderate energy restriction for obese women. Current
      controversies in GDM nutrition therapy involve manipulation of dietary
      composition (amounts and types of carbohydrates and fats), gestational weight
      gain, and energy and carbohydrate restriction. Randomized controlled trials are
      needed to determine which dietary compositions and patterns promote normoglycemia
      as well as optimal maternal and infant outcomes. Until better evidence is
      available, nutrition therapy will remain a cornerstone of GDM management with
      potential benefits that cannot be fully realized in clinical practice.

PMID- 15461905
TI  - Effectiveness of weight loss and maintenance interventions in women.
AB  - Overweight and obesity in women contribute to increased risk of many health
      problems, including type 2 diabetes. A systematic review of the weight loss
      literature found 17 articles in which women were the sole subjects and studies
      were a minimum of 1 year or longer in duration. Data were pooled and average
      weight loss and maintenance for women at 6 and 12 months was determined for each
      of the six interventions. Diet as the primary intervention resulted in a weight
      loss of approximately 7 kg at 6 months (approximately 13% of their initial
      weight), which was maintained to 12 months. When specific goals for physical
      activity or weight loss medications were combined with diet, better outcomes were
      experienced. Regardless of the intervention, at approximately 6 months a weight
      loss plateau occurred. All of the studies included at least monthly follow-up.

PMID- 15461906
TI  - Which patients are good candidates for synthetic mid-urethral slings?

PMID- 15461908
TI  - A review of quality-of-life questionnaires for urinary incontinence and
      overactive bladder: which ones to use and why?
AB  - Overactive bladder (OAB) and stress urinary incontinence have a profound impact
      on patients' health-related quality of life (HRQL). The purpose of this article
      is to identify and describe condition-specific HRQL measures validated among
      patients with symptoms of OAB or stress urinary incontinence. A Medline
      literature search was performed to identify published articles or abstracts
      focusing on the development and psychometric validation of relevant instruments.
      Target populations and psychometric properties (reliability, validity,
      responsiveness to change) of 16 questionnaires are reviewed. A range of well
      validated, condition-specific HRQL measures are available. Recommendations are
      provided regarding which measures to use in different situations. When choosing
      among instruments, psychometric evidence and the match of an instrument to the
      study population should be considered.

PMID- 15461909
TI  - Urodynamics in the era of tension-free slings: defining the role.
AB  - The role of urodynamics in the routine preoperative evaluation of women with
      stress urinary incontinence is controversial. The introduction of tension-free
      mid-urethral sling procedures has created a new paradigm in surgical management.
      The capability of performing these procedures on an ambulatory basis has created
      more uncertainty about the use of urodynamic testing. The long-term results of
      these procedures in patients with intrinsic sphincteric deficiency, mixed
      incontinence, and voiding dysfunction are not clearly known. This article reviews
      the mechanism of action and results of tension-free slings and proposes a
      rational role for urodynamic testing in patients considered for these procedures.

PMID- 15461910
TI  - Cerebral control of bladder function.
AB  - Symptoms such as overactive bladder represent disorders of bladder control.
      Functional brain scanning by positron emission tomography and functional magnetic
      resonance imaging suggest that normal control is exerted by a network of regions
      in the emotional nervous system, including periaqueductal gray, thalamus, insula,
      anterior cingulate, and prefrontal cortex. The network receives afferent signals,
      converts them to bladder sensations, and brings them to conscious attention,
      together with an unpleasant affect (desire to void) that motivates bladder
      emptying and thus maintains homeostasis. In patients with poor control, brain
      response to bladder filling differs; cerebral control is abnormal, even in the
      absence of involuntary detrusor contraction. Behavioral therapy and electrical
      stimulation appear to be possible treatments.

PMID- 15461911
TI  - Detrusor after-contraction: is this important?
AB  - A sudden increase in detrusor pressure after cessation of voiding detrusor
      contraction and in the absence of flow can be recorded in some cystometric
      tracings and has been defined as detrusor after-contraction. Although it has been
      described in medical literature since the late 19th century, no common definition
      had been found by the authors of the relatively few articles published on the
      subject. This review was conducted by analyzing the available literature on the
      topic in an attempt to understand its real significance and clinical impact and
      has revealed several controversial aspects to the problem of detrusor after
      contraction. These aspects include its prevalence in various groups of patients
      studied urodynamically, its definition, and its clinical significance.

PMID- 15461912
TI  - Preview of new drugs for overactive bladder and incontinence: darifenacin,
      solifenacin, trospium, and duloxetine.
AB  - This year, the US Food and Drug Administration will approve four new drugs
      indicated for the treatment of lower urinary tract dysfunction. Darifenacin,
      solifenacin, and trospium are antimuscarinic agents aimed at relieving the
      symptoms of overactive bladder and urge incontinence in men and women. Duloxetine
      will be the first drug approved for the treatment of female stress urinary
      incontinence. This article presents current data on the efficacy and tolerability
      of these new agents and invites the reader to decide whether they offer any
      potential advantages over existing therapies.

PMID- 15461916
TI  - Synthetic sling options for stress urinary incontinence.
AB  - In the past decade, sling surgery has become the preferred technique for the
      management of female stress urinary incontinence. A greater understanding of the
      pathogenesis of stress urinary incontinence and a greater durability and
      effectiveness for sling surgery has allowed this technique to become the
      benchmark for treatment of female stress urinary incontinence. As a consequence,
      a multitude of products have been developed using various techniques and
      materials to perform sling surgery. This article reviews the materials and
      techniques available and the complications associated with each. Most
      importantly, the outcomes are discussed so that the readers can best understand
      the impact of these surgeries on our patients.

PMID- 15461917
TI  - Urologic applications of botulinum toxin therapy for voiding dysfunction.
AB  - Botulinum toxin is primarily a presynaptic neuromuscular blocking agent inducing
      selective and reversible muscle weakness up to several months when injected
      intramuscularly in small quantities. The clinical use of botulinum toxin type-A
      has gained widespread acceptance and application for numerous adult and pediatric
      spasticity syndromes. This has led to the urologic adoption of this minimally
      invasive therapy for the treatment of idiopathic and neurogenic detrusor
      overactivity, interstitial cystitis, detrusor-sphincter dyssynergia, urinary
      retention, and prostatic conditions. Outlined below is an overview of the
      clinical adoption of this therapy for the treatment of various dysfunctions of
      the lower urinary tract.

PMID- 15461918
TI  - Sling failures: what's next?
AB  - The pubovaginal sling has been used to treat anatomic, functional, and recurrent
      stress urinary incontinence for decades with excellent results. Nevertheless,
      enthusiasm for the pubovaginal sling is tempered by the surgical morbidity and
      postoperative voiding dysfunction associated with it. New modifications such as
      alternative sling materials, bone anchor suspension, and midurethral slings have
      been developed to reduce operating time and surgical morbidity. The less invasive
      approaches are now well recognized and midurethral slings have become the most
      common procedure performed for stress urinary incontinence. Despite the ubiquity
      of sling procedures in all of their forms, there is no consensus on the
      management of sling failures. Recent literature suggests that similar to primary
      genuine stress incontinence, recurrent stress urinary incontinence as a result of
      sling failure is being successfully managed with less invasive techniques.

PMID- 15461919
TI  - The use of graft materials in anterior compartment pelvic reconstruction.
AB  - Since 1996, the number of reports in the urologic and gynecologic literature
      using synthetic and allograph prosthetics to enhance the durability of anterior
      compartment repairs have increased significantly. Central to the use of these
      prosthetics is long-term follow-up to demonstrate that their use actually confers
      a benefit to patients and surgeons alike. This review attempts to catalog those
      reports and the outcomes, with an emphasis on the cadaveric prolapse repair with
      sling, which is used by the authors for repair of anterior compartment prolapse
      with overt or occult genuine stress urinary incontinence.

PMID- 15461920
TI  - Female sexual dysfunction following vaginal surgery: myth or reality?
AB  - This article reviews the mechanisms by which vaginal surgery affects female
      sexual function and related pathophysiology to potential causes. The anatomy,
      neurovascular supply of the clitoris and introitus, and intrapelvic nerve supply
      are discussed as they apply to vaginal surgery. Methods to avoid neurovascular
      damage during pelvic floor surgery have been corroborated by supporting
      literature. The incidence of female sexual dysfunction after various transvaginal
      procedures for indications such as stress urinary incontinence and pelvic organ
      prolapse, anterior/posterior colporrhaphy, perineoplasty, and vaginal vault
      prolapse has been discussed. Current literature regarding female sexual
      dysfunction following other procedures such as vaginal hysterectomy, Martius flap
      interposition, and vesicovaginal and rectovaginal fistula repair also are
      reviewed.

PMID- 15461921
TI  - Management of Primary Hypertensive Hemorrhage of the Brain.
AB  - Intracerebral hemorrhage (ICH) can be prevented by adequate treatment of
      hypertension. Angiotensin-converting enzyme inhibitors, angiotensin receptor
      blockers, and calcium channel blockers seem particularly effective. ICH also is
      associated with apolipoprotein E 4 genotype and with low cholesterol, but not
      statin therapy for high cholesterol. Microbleeds identified on magnetic resonance
      imaging scans also confer increased risk of ICH. Experimental drug regimens that
      target metalloproteinases and inflammation reduce damage in animal models of ICH,
      but none are proven effective in humans. Cerebral edema after ICH has varied
      mechanisms and significance, and may be another target for therapy. Cerebral
      blood flow is not substantially reduced in most patients with ICH. Lowering
      systolic blood pressure below 160 mm Hg in the first hours after ICH may prevent
      additional bleeding. Activated factor 7 is a promising new therapy to limit
      hematoma enlargement and consequently reduce morbidity and mortality after ICH.
      Dosages of 80 to 160 MUg/kg given within the first 3 to 4 hours after symptom
      onset, or in patients at risk of additional bleeding such as those with
      coagulopathy, is logical but is unapproved. The role of activated factor 7
      hopefully will be clarified by additional study. Open surgical evacuation of most
      spontaneous supratentorial hematomas has been shown to be ineffective in reducing
      mortality or disability except in certain circumstances, such as large or
      enlarging superficially located clots in patients who are awake. Stereotactic and
      endoscopic clot aspiration, often using instillation of lytic agents to liquefy
      the hematoma, is the most active area of surgical intervention research. Such
      minimally invasive approaches have been shown to safely produce more rapid
      removal of blood compared with standard treatment. This is particularly true for
      intraventricular hemorrhages. Future research will focus on the use of stem cells
      to restore the damaged architecture around the hematoma. The impressive scope and
      progress of ongoing clinical and basic research show that there is no longer a
      place for nihilism in the approach to ICH.

PMID- 15461922
TI  - Type 2 Diabetes Mellitus and Insulin Resistance: Stroke Prevention and
      Management.
AB  - Clinically recognized disorders of glucose metabolism include impaired fasting
      glucose, impaired glucose tolerance (both termed prediabetes), and diabetes
      mellitus. Type 2 diabetes mellitus affects 6% to 13% of adults in the United
      States. Among patients with recent stroke, 70% will have known diabetes, occult
      diabetes (detectable on an oral glucose tolerance test), or prediabetes. Type 2
      diabetes mellitus is associated with a two- to six-fold increased risk for first
      or recurrent ischemic stroke. The mechanisms for the association are myriad and
      include the effects of hyperglycemia on vascular tissues and coagulation, and
      aberrations in blood pressure regulation, lipid metabolism, endothelial function,
      vascular inflammation, lipid metabolism, smooth muscle cell proliferation, and
      fibrinolysis. The most effective strategies to prevent stroke among people with
      diabetes include blood pressure control, antiplatelet therapy, and statin
      therapy. Tight glycemic control is recommended to prevent microvascular disease,
      but the effect on macrovascular disease, including stroke, has not been proven.
      Target blood pressure should be less than 130/80. Antiplatelet therapy may be
      accomplished with 81 to 325 mg of aspirin daily or 75 mg of clopidogrel daily.
      Statins should be given in dosages effective to reduce low-density lipoprotein
      cholesterol to less than 100 mg/dL. For glycemic control, first line therapy for
      most patients is metformin, starting at 500 mg daily. With time, most patients
      will need two or three oral medications from different classes and many
      eventually will require insulin therapy. Prevention of diabetes may be best
      accomplished by identifying those at risk and modifying diet, weight, and
      exercise habits. Screening for prediabetes and diabetes is appropriate for men
      and women older than 45 years and all individuals with vascular disease. Insulin
      resistance and impaired insulin secretion is the major underlying defect in type
      2 diabetes mellitus. It also affects 50% of nondiabetic subjects with a recent
      ischemic stroke. Emerging evidence has linked insulin resistance to the
      pathophysiologic derangements in type 2 diabetes mellitus that accelerate
      atherosclerosis. Treatment of insulin resistance with weight loss, exercise, or
      medication can correct these derangements, and represents a promising approach to
      stroke prevention.

PMID- 15461923
TI  - Treatment Options for Unruptured Cerebral Aneurysm.
AB  - The management of unruptured cerebral aneurysm is controversial. Because the
      natural history of unruptured cerebral aneurysm is not well defined, the best
      management strategy is unclear. The current consensus on the management of
      unruptured cerebral aneurysm includes observation, microsurgical clipping, and
      endovascular treatment. The methodologies used to follow up a known unruptured
      aneurysm are controversial and may be dependent on the preferences of the
      treating physician. Most aneurysms are managed by the neurosurgeons and
      interventional neuroradiologists, but neurologists often are the first to
      discover the unruptured aneurysms when screening the patients for other
      neurologic disorders. Therefore, the knowledge on when to screen patients for and
      how to best manage an unruptured aneurysm will have a direct impact on their
      daily practices. Unruptured aneurysms often cause other neurologic symptoms
      including ischemic events, seizures, and headache. These symptoms may prompt more
      interventional treatment. Without a thoughtfully designed, true population-based
      study or randomized trial, the current best management will be based on the
      available literature and the temporal profile of each patient.

PMID- 15461924
TI  - Estrogens and Stroke: Use of Oral Contraceptives and Postmenopausal Use of
      Estrogen: Current Recommendations.
AB  - Stroke in women is a major medical problem. More than half of all strokes occur
      in women and women account for nearly 60% of stroke-related deaths. The current
      generation of oral contraceptives may be associated with an increased risk for
      stroke. However, the absolute risk is small (less than the mortality associated
      with pregnancy). Women older than 35 years who use oral contraceptives,
      especially women with hypertension, smoking, or migraines, seem to be the group
      at greatest risk for stroke. Some guidelines advise against the use of oral
      contraceptives in these groups. Postmenopausal hormone therapy is not effective
      for reducing the risk of a first stroke. It also is not effective for reducing
      the risk of a recurrent myocardial infarction, death, and/or stroke among women
      with myocardial infarction. Postmenopausal hormone therapy is not effective for
      reducing the risk of a recurrent stroke or death among women with a recent TIA or
      stroke. Among women who have had a stroke and are taking hormone replacement
      therapy, there may be an increased risk of fatal (recurrent) stroke. There also
      may be a more severe impairment after a recurrent stroke among women using
      hormone replacement therapy. Results similar to those for cerebrovascular disease
      have been found with cardiovascular disease for primary and secondary prevention
      (no evidence for efficacy). Physician judgment is required with nonvascular
      indications for postmenopausal hormone therapy. The reported absolute reported
      rates of stroke, myocardial infarction, and vascular death although low can help
      inform physicians to make a more realistic assessment of the risks and benefits
      of hormone therapy among postmenopausal women.

PMID- 15461925
TI  - Overview of Pediatric Headache.
AB  - There is a high prevalence of headache disorders in children and adolescents.
      Headache in pediatric population is substantially underdiagnosed and
      undertreated. The recently revised International Headache Society criteria are a
      step in the right direction to improve our diagnostic accuracy. The recent
      increases in evidence-based data in the pediatric headache population will help
      to outline appropriate management strategies for acute and preventive treatment.
      In this article, diagnostic and treatment issues related to the pediatric
      headache patient will be reviewed.

PMID- 15461926
TI  - Menstrual Migraine.
AB  - The initial treatment of menstrual migraine (MM) should be the same as that of
      migraine that occurs at any other time during the month and should include
      lifestyle modifications and the use of appropriate acute therapies aimed at
      decreasing attack symptoms, duration, and disability. If results of acute therapy
      are incomplete or unsatisfactory, then preventive strategies may be required.
      Comorbidities may, however, influence choice of preventive therapy or accelerate
      initiation of preventive therapy. Comorbid dysmenorrhea, menometrorrhagia, and
      endometriosis argue for early use of hormonal therapies. Hormonal strategies may
      be appropriate because the premenstrual decline in estradiol concentration
      predictably precipitates MM, and targeting and preventing this decline can
      decrease headache occurrence. Continuous combined hormonal contraceptives can
      reduce hormone fluctuations and, for some MM sufferers, can deliver more than
      contraceptive benefits. Nonsteroidal anti-inflammatory drugs are appropriate for
      treatment of co-occurring dysmenorrhea or when hormonal strategies are
      contraindicated; their efficacy may be caused partly by the role of
      prostaglandins in MM and dysmenorrhea. As with the use of hormonal therapy, use
      of nonsteroidal anti-inflammatory drugs allows for treatment of breakthrough
      headache with triptans. Results of clinical trials suggest that daily use of
      triptans in the menstrual window may bring about as much as 50% reduction in
      headache frequency, but such use still requires acute treatment of breakthrough
      headache and adherence to daily triptan limits. Use of this strategy requires
      that headache occurrence be highly predictable.

PMID- 15461927
TI  - Headache Caused by Giant Cell Arteritis.
AB  - Giant cell arteritis (GCA) is the most common primary systemic vasculitis in
      older adults. Patients usually are older than 50 years and have an erythrocyte
      sedimentation rate (Westergren) greater than 50 mm/h. Headache is a common
      symptom, occurring in approximately 90% of patients. However, the most serious
      complications of GCA, blindness and stroke, may occur in the absence of headache.
      Nonspecific constitutional symptoms such as weight loss, fever, and malaise may
      dominate the clinical presentation. Currently, corticosteroids are the mainstay
      of therapy for GCA. Treatment is initiated at 0.7 to 1 mg/kg mg of prednisone (or
      equivalent) per day as soon as the diagnosis is suspected. The medication is
      tapered based on laboratory parameters and symptoms. Relapse is common,
      especially during the first year of therapy. Side effects from steroids in the
      elderly are common and often serious. Steroid resistance (manifesting as
      continued high dose requirements after 3 to 6 months) may complicate therapy and
      place patients at increased risk of side effects. Methotrexate and azathioprine
      have been used as steroid-sparing agents based on anecdotal evidence. More
      recently, evidence is emerging that antitumor necrosis factor-alpha agents may be
      efficacious and act as steroid-sparing agents. New-onset headache or worsening
      headache in a patient older than 50 years should raise the possibility of GCA and
      appropriate therapeutic and diagnostic measures should be begun promptly.

PMID- 15461928
TI  - Posttraumatic Headache.
AB  - Posttraumatic headache (PTH) is divided into acute and chronic groups whose
      management and prognosis are clearly different. Although IHS criteria stipulate
      that PTH should have an onset within 2 weeks of the trauma, it has been observed
      that a headache linked to the trauma can start later. PTH can be clinically
      divided into the following groups: migraine-like headache, tension-type-like
      headache, cluster-like headache, cervicogenic-like headache, and others. Based on
      these clinical distinctions, therapy can be administered accordingly. However,
      the distinction is relative and numerous clinical features may be common to all.
      There seems to be a weak inverse relationship between the severity of the head
      trauma and the occurrence of a PTH, especially chronic. A holistic approach is
      not only useful but it is necessary for a therapeutic success. Early and
      aggressive treatment and empathy are essential to the patient's improvement.
      Prompt recognition and treatment of laceration, peripheral nociceptive sources
      such as cervical joint displacement, vascular factors, may diminish chronicity.
      Neuromodulation of pain with prophylactic agents is recommended early. Although
      it is less necessary for the acute PTH, it will be crucial for the chronic form
      and should be initiated no later than 2 months cut-off time between acute and
      chronic PTH. Recognition and treatment of psychiatric factors such as depression
      and anxiety will lessen the risk of chronicity. Analgesic rebound-withdrawal
      headache commonly is seen in chronic PTH. This must be corrected rapidly because
      it can protract the headache and render other inappropriate therapeutic measures
      inefficient.

PMID- 15461930
TI  - Arsenic trioxide liposomes: encapsulation efficiency and in vitro stability.
AB  - The use of arsenic-containing compounds in cancer therapy is currently being re
      considered, after the recent approval of arsenic trioxide (Trisenox) for the
      treatment of relapsed promyelocytic leukemia (PML). In an attempt to prepare a
      carrier system to minimize the toxicity of this drug, the aim of this study is to
      prepare and characterize liposomes encapsulating arsenic trioxide (ATO). For
      this, we prepared different types of liposomes entrapping ATO: large
      multilamellar (MLV), sonicated (SUV) and dried reconstituted vesicles (DRV). The
      techniques used were: thin film hydration, sonication and the DRV method,
      respectively. Two lipid compositions were studied for each liposome type,
      EggPC/Chol (1:1) and DSPC/Chol (1:1). After liposome preparation, drug
      encapsulation was evaluated by measuring arsenic in liposomes. For this, energy
      dispersive X-ray fluorescence spectroscopy or atomic absorption was used. In
      addition, the retention of the drug in the liposomes was evaluated after
      incubating the liposomes in buffer at 37 degrees C. The experimental results
      reveal that encapsulation of ATO in liposomes ranges between 0.003 and 0.506 mol/
      mol of lipid, and is highest in the DRV vesicles and lowest in the small
      unilamellar vesicles, as anticipated. Considering the in vitro stability of ATO
      encapsulating liposomes: 1) For the PC/Chol liposomes (DRV and MLV), after 24
      hours of incubation, more than 70% (or 90% in some cases) of the initially
      encapsulated amount of ATO was released. 2) The liposomes composed of DSPC/Chol
      could retain substantially higher amounts of ATO, especially the DRV liposomes
      (54% retained after 24 h). 3) In the case of PC/Chol, temperature of incubation
      has no effect on the ATO release after 24 hours, but affects the rate of ATO
      release in the MLV liposomes, while for the DSPC/Chol liposomes there is a slight
      increase (statistically insignificant) of ATO release at higher temperature.

PMID- 15461929
TI  - Transendothelial movement of liposomes in vitro mediated by cancer cells,
      neutrophils or histamine.
AB  - A two-chamber culture system has been used to examine the ability of small
      liposomes to cross an endothelial cell barrier in response to various stimuli.
      Transendothelial transit of liposomes was almost negligible in the presence of
      intact, healthy endothelial cells (EC). Addition of histamine induced a
      concentration-dependent increase in the movement of liposomes across the EC
      monolayer. In the presence of polymorphonuclear neutrophils (PMNs), migrating in
      response to a chemotactic gradient of N-Formil-Met-Leu-Phe (fMLP), both liposomes
      and IgG crossed EC monolayer by a paracellular pathway, largely independent of an
      association with the PMNs. The presence of cancer cell, growing in the lower
      chamber or the presence of cancer cell-conditioned media, also resulted in the
      passage of liposome across the EC. We conclude that EC monolayers are
      sufficiently disrupted by several physiologically relevant stimuli to allow for
      the transendothelial passage of liposomes. These results have important
      implications for the therapeutic use of liposome in the treatment of cancer or
      other inflammatory processes.

PMID- 15461931
TI  - Dipalmitoylphosphatidylcholine (DPPC) and DPPC/cholesterol liposomes as
      predictors of the cytotoxicity of bis-GMA related compounds.
AB  - In light of recent development, dental materials such as 2, 2-bis [4-2(-hydroxy-3
      methacryloyloxypropoxy)phenyl] propane, ( bis-GMA); 2, 2-bis [4-(1-hydroxymethyl
      2-methacryloxy)phenyl] propane, (iso-bis-GMA); and triethyleneglycol
      dimethacrylate, (TEGDMA) were investigated to determine whether their phase
      transition properties (phase transition temperature, temperature width,
      cooperativity) could be induced in samples of DPPC or DPPC/cholesterol (CHOL)
      liposomes using differential scanning calorimetry (DSC). The changes in phase
      transition properties of DPPC liposomes caused by addition of TEGDMA were greater
      than those caused by addition of bis-GMA or iso-bis-GMA, but the extent of
      changes in the properties of DPPC/CHOL (10:1 or 4:1) liposomes declined in the
      order of bis-GMA > iso-bis-GMA > TEGDMA. The degree of alteration was related to
      the cytotoxicity of these compounds. DPPC/CHOL liposomes were found to be better
      predictors of cytotoxicity than DPPC liposomes. Whether the computational
      approach to studying the molecular mechanism of alteration is applicable using
      descriptors such as reactivity of energy of the highest occupied molecular
      orbital (HOMO) and/or lowest unoccupied molecular orbital (LUMO) was
      investigated, and the data suggested that these descriptors are useful for
      studying the interactive roles of dental materials.

PMID- 15461932
TI  - Influence of liposomal local anesthetics on platelet aggregation in vitro.
AB  - We assessed the effect of local anesthetics (LA) from different families such as
      esters (benzocaine), linear aminoamides (lidocaine) and cyclic aminoamides
      (bupivacaine) on the platelet aggregation induced by ADP. Liposomal formulations
      of the three LA, prepared with egg phosphatidylcholine:cholesterol alpha
      tocopherol, were also tested. The three LA were able to inhibit platelet
      aggregation induced by ADP, in the following order: bupivacaine > lidocaine >
      benzocaine. After encapsulation into liposomes the inhibitory effect increased
      for all anesthetics studied, showing that aggregation tests could be used to
      assess the toxicity of new drug formulations.

PMID- 15461933
TI  - Electron cryo-microscopy reveals mechanism of action of propranolol on artificial
      membranes.
AB  - The pharmacological activity of several amphiphilic drugs is often related to
      their ability to interact with biological membranes. Propranolol is an efficient
      multidrug resistance (MDR) modulator; it is a nonselective beta-blocker and is
      thought to reduce hypertension by decreasing the cardiac frequency and thus blood
      pressure. It is used in drug delivery studies in order to treat systemic
      hypertension. We are interested in the interaction of propranolol with artificial
      membranes, as liposomes of controllable size are used as biocompatible and
      protective structures to encapsulate labile molecules, such as proteins, nucleic
      acids or drugs, for pharmaceutical, cosmetic or chemical applications. We present
      here a study of the interaction of propranolol, a cationic surfactant, with pure
      egg phosphatidylcholine (EPC) vesicles. The gradual transition from liposome to
      micelle of EPC vesicles in the presence of propranolol was monitored by time
      resolved electron cryo-microscopy (cryo-EM) under different experimental
      conditions. The liposome-drug interaction was studied with varying drug/lipid
      (D/L) ratios and different stages were captured by direct thin-film
      vitrification. The time-series cryo-EM data clearly illustrate the mechanism of
      action of propranolol on the liposome structure: the drug disrupts the lipid
      bilayer by perturbing the local organization of the phospholipids. This is
      followed by the formation of thread-like micelles, also called worm-like micelles
      (WLM), and ends with the formation of spherical (globular) micelles. The overall
      reaction is slow, with the process taking almost two hours to be completed. The
      effect of a monovalent salt was also investigated by repeating the lipid
      surfactant interaction experiments in the presence of KCl as an additive to the
      lipid/drug suspension. When KCl was added in the presence of propranolol the
      overall reaction was the same but with slower kinetics, suggesting that this
      monovalent salt affects the general lipid-to-micelle transition by stabilizing
      the membrane, presumably by binding to the carbonyl chains of the
      phosphatidylcholine.

PMID- 15461934
TI  - Encapsulation of enrofloxacin in liposomes I: preparation and in vitro
      characterization of LUV.
AB  - Liposomes are effectively used in the treatment of microbial infections. Higher
      cellular uptake has been reported when antibiotics are encapsulated in liposomes.
      In this study, enrofloxacin (ENF) was encapsulated in large unilamellar vesicles
      (LUVs) and the effects of formulation variables on the liposome characteristics
      were investigated. Liposomes were prepared using dry lipid film method. A number
      of variables such as molar ratios of phospholipid (DPPC; DL-alpha
      phosphatidylcholine dipalmitoyl), cholesterol, ENF and amount of alpha-tocopherol
      and the volumes of internal (chloroform) and external phases [phosphate buffered
      saline PBS (pH 7.4)] were studied. In vitro characterization of the liposomes
      including the encapsulation capacity, size and drug release properties were
      carried out. Using of this method, spherical LUV liposomes with high drug content
      could be produced. Particle size of liposomes changed between 3.12 and 4.95
      microm. The molar ratios of DPPC, cholesterol and ENF affected the size of the
      liposome (p < 0.05). The drug encapsulation capacities were high and changed
      between 37.1% and 79.5%. The highest ENF encapsulation was obtained with the
      highest cholesterol content. An increase in the drug encapsulation capacity of
      the liposome was found with increasing molar ratios of DPPC, cholesterol and ENF
      (p < 0.05). Furthermore, the release of ENF from the liposomes decreased as the
      molar ratios of DPPC, cholesterol and ENF increased (p < 0.05). In conclusion, a
      convenient colloidal carrier for the controlled release of ENF can be prepared by
      changing the formulation parameters of LUVs.

PMID- 15461935
TI  - Novel camptothecin analogue (gimatecan)-containing liposomes prepared by the
      ethanol injection method.
AB  - Small-sized liposomes have several advantages as drug delivery systems, and the
      ethanol injection method is a suitable technique to obtain the spontaneous
      formation of liposomes having a small average radius. In this paper, we show that
      liposomal drug formulations can be prepared in situ, by simply injecting a drug
      containing lipid(s) organic solution into an aqueous solution. Several parameters
      should be optimized in order to obtain a final suitable formulation, and this
      paper is devoted to such an investigation. Firstly, we study the liposome size
      distributions determined by dynamic light scattering (DLS), as function of the
      lipid concentration and composition, as well as the organic and aqueous phases
      content. This was carried out, firstly, by focusing on POPC (1-palmitoyl-2-oleoyl
      sn-glycero-3-phosphocholine) then on the novel L-carnitine derivative PUCE
      (palmitoyl-(R)-carnitine undecyl ester chloride), showing that it is possible to
      obtain monomodal size distributions of rather small vesicles. In particular,
      depending on the conditions, it was possible to achieve a population of liposomes
      with a mean size of 100 nm, when a 50 mM POPC ethanol solution was injected in
      pure water; in the case of 50 mM PUCE the mean size was around 30 nm, when
      injected in saline (0.9% NaCl). The novel anticancer drug Gimatecan, a
      camptothecin derivative, was used as an example of lipophilic drug loading by the
      injection method. Conditions could be found, under which the resultant liposome
      size distributions were not affected by the presence of Gimatecan, in the case of
      POPC as well as in the case of PUCE. To increase the overall camptothecin
      concentration in the final liposomal dispersion, the novel technique of "multiple
      injection method" was used, and up to a final 5 times larger amount of liposomal
      drug could be reached by maintaining approximately the same size distribution.
      Once prepared, the physical and chemical stability of the liposome formulations
      was satisfactory within 24, as judged by DLS analysis and HPLC quantitation of
      lipids and drug. The Gimatecan-containing liposomes formulations were also tested
      for in vitro and in vivo activity, against the human nonsmall cell lung carcinoma
      NCI-H460 and a murine Lewis lung carcinoma 3 LL cell lines. In the in vitro
      tests, we did not observe any improvement or reduction of the Gimatecan
      pharmacological effect by the liposomal delivery system. More interestingly, in
      the in vivo Lewis lung carcinoma model, the intravenously administration of
      liposomal Gimatecan formulation showed a mild but significant increase of Tumor
      Volume Inhibition with respect to the oral no-liposomal formulation (92% vs. 86
      %, respectively; p < 0.05). Finally, our study showed that the liposomal
      formulation was able to realize a delivery system of a water-insoluble drug,
      providing a Gimatecan formulation for intravenous administration with a preserved
      antitumoral activity.

PMID- 15461937
TI  - [Spanish scientific publications on hepatitis C virus. A Medline study (1980
      2002)].
AB  - BACKGROUND: To analyze the scientific publications on hepatitis C virus infection
      from Spanish hospitals between 1980 and 2002. METHOD: Articles published from
      January 1980 to December 2002 and contained in the Medline database were selected
      using the following key words: "Hepatitis C" [MeSH] AND ((Spain [AD] OR Espana
      [AD] OR Spanien [AD] OR Espagne [AD] OR Espanha [AD]) OR (Spanish [LA]) OR
      Spain)). Geographical and institutional distribution, national or international
      publication, subject matter of the article, and date of publication were
      recorded. Bibliometric indicators of output and impact were estimated. RESULTS: A
      total of 1.051 articles were studied, of which 346 were excluded. The number of
      articles published increased from 0 in 1980 to 121 in 1998 and decreased to 36 in
      2002. More articles were published in international journals than in Spanish
      journals (59.2% versus 40.8%). The main topic was epidemiology (28.6%) in the
      first decade and treatment (20.2%) in the second. Original articles were the most
      common type of article (80.5%). The centers with the greatest output were
      Hospital Clinic in Barcelona (11.6%), Vall d'Hebron Hospital (8.9%) in Barcelona
      and Fundacion Jimenez Diaz in Madrid (8.9%). The mean impact factor increased
      linearly from 0 in 1980 to 3 in 2002. CONCLUSIONS: The number and impact factor
      of scientific publications on hepatitis C virus by Spanish authors has grown
      significantly during the last 2 decades.

PMID- 15461936
TI  - [Evaluation of Helicobacter pylori susceptibility to rifaximin].
AB  - INTRODUCTION: Helicobacter pylori infection affects more than half the world's
      population. It is a major cause of chronic gastritis and there is a strong
      association with peptic ulceration and gastric adenocarcinoma. Rifaximin is a new
      nonabsorbable broad-spectrum antimicrobial agent that reaches high concentrations
      in the gastrointestinal tract. AIM: To evaluate the in vitro activity of
      rifaximin against H. pylori isolates. METHODS: Thirty-one H. pylori strains were
      analyzed by the agar dilution method. Clarithromycin was used as the control
      antibiotic. Staphylococcus aureus and Streptococcus pneumoniae were used as
      quality control strains. Plates were read at days 4 and 7 of incubation. The
      MIC50 and MIC90 of each antibiotic were calculated. Strains with a clarithromycin
      MIC of > 1 microg/ml were considered resistant. RESULTS: The MIC50 of
      clarithromycin at days 4 and 7 was 0.125 microg/ml and the MIC90 at days 4 and 7
      ranged from 8 to 16 microg/ml, respectively. The MIC50 of rifaximin at days 4 and
      7 ranged from 1 to 2 microg/ml, respectively, and the MIC90 was 4 microg/ml at
      both days 4 and 7. Twenty percent of H. pylori strains were resistant to
      clarithromycin. All clarithromycin-resistant strains were inhibited at a maximal
      rifaximin concentration of 4 microg/ml. CONCLUSION: These results indicate that
      this new antibiotic may be useful for eradication of H. pylori infection. Because
      rifaximin is active against H. pylori strains resistant to clarithromycin, it
      could be useful in combination with this drug or in the treatment of therapeutic
      failure.

PMID- 15461938
TI  - [Utility of endoscopy in digestive hemorrhage due to vasculitis].
AB  - Vasculitides constitute a heterogeneous group of diseases characterized by
      inflammation of blood vessels. The skin is mainly affected, although the
      gastrointestinal tract mucosa can also be involved. The contribution of endoscopy
      in these cases has not been clearly determined. We report three cases of systemic
      vasculitis (polyarteritis nodosa, Schonlein-Henoch purpura and Behcet's disease)
      presenting with acute digestive bleeding. Endoscopy was an effective technique
      for completing the diagnosis and in establishing an effective nonsurgical
      therapeutic approach in these potentially lethal cases of gastrointestinal
      hemorrhage.

PMID- 15461939
TI  - [Chronic hepatitis C and celiac sprue: an infrequent association].
AB  - Celiac sprue (CS) has been described in association with hepatitis C virus (HCV)
      as another immunologic manifestation of this infectious disease. We report 2
      patients, a 42-year-old woman and a 59-year-old man, with chronic HCV hepatitis.
      Upper digestive endoscopy and duodenal biopsy were performed to investigate
      diverse symptoms. The results of histological analysis and serological study were
      compatible with CS. The association between both diseases, including
      immunological aspects and the implications of anti-HCV treatment, is discussed.

PMID- 15461940
TI  - [Endoscopic resection with polypectomy snare and argon plasma coagulation in
      early gastric adenocarcinoma in a patient at high surgical risk].
AB  - We report a patient at high surgical risk with an early gastric adenocarcinoma.
      Due to the size of the tumor, endoscopic mucosal resection alone was not feasible
      and consequently a combination of endoscopic resection with polypectomy snare and
      argon plasma coagulation was applied. Four years later the patient remains
      asymptomatic.

PMID- 15461941
TI  - [Hemoperitoneum secondary to spontaneous rupture of the umbilical vein].
AB  - Patients with ascites can develop spontaneous hemoperitoneum after injury or as a
      complication of diagnostic or therapeutic techniques. Spontaneous rupture of
      intra-abdominal varices is a rare complication of portal hypertension and an
      infrequent cause of hemoperitoneum that causes high mortality (75%). We present a
      new case of spontaneous hemoperitoneum secondary to umbilical vein rupture in a
      male patient with liver cirrhosis and review the cases previously described in
      the literature.

PMID- 15461942
TI  - [Osteopenia and osteoporosis in inflammatory bowel disease].

PMID- 15461943
TI  - [Liver transplantation in patients with HIV infection].

PMID- 15461944
TI  - [Gastric stromal tumor].

PMID- 15461945
TI  - [Infliximab as treatment for a severe outbreak of ulcerative colitis].

PMID- 15461946
TI  - [Giant esophageal fibrovascular polyp].

PMID- 15461947
TI  - [Safety and efficacy of of adefovir dipivoxil in the treatment of patients with
      chronic hepatitis B-related liver disease].

PMID- 15461948
TI  - [Spontaneous bacterial peritonitis due to Streptococcus salivarius in cirrhotic
      man].

PMID- 15461950
TI  - [Redefinition of the concept of gene].

PMID- 15461949
TI  - [Peripheral facial paralysis during interferon treatment in hepatitis C: recovery
      without antiviral therapy withdrawal].

PMID- 15461952
TI  - [The frog who wished to be as big as an ox: characterization in amphibians of a
      novel neuropeptide that stimulates appetite in mammals].

PMID- 15461953
TI  - [Ascorbic acid: a first generation drug for Charcot-Marie-Tooth disease].

PMID- 15461954
TI  - [Dissecting cytokinesis: proteomic and genomic approaches].

PMID- 15461955
TI  - [mtDNA mutator mice: an ageing model].

PMID- 15461956
TI  - [Clinical application of gene-expression profiling in lymphome].

PMID- 15461958
TI  - [Axon guidance at the midline gets more complex].

PMID- 15461959
TI  - [Three DNA strands in the catalytic center of DNA polymerases].

PMID- 15461960
TI  - [The multiple roles of FOXO transcription factors].

PMID- 15461961
TI  - [These 1.4% which separate us from the chimpanzees!].

PMID- 15461963
TI  - [Contributions and limits of the diagnosis of human African trypanosomiasis].
AB  - Human African trypanosomiasis, or sleeping sickness, is still a worrying problem
      in Africa. Sleeping sickness is a disease for which a systematic monitoring is
      necessary, particularly for the trypanosomiasis caused by Trypanosoma brucei
      gambiense, which is characterized by a long asymptomatic stage. In the absence of
      specific clinical signs, mass screening of populations remains the only way to
      control the disease and to avoid its spreading. The lack of sensitivity and
      specificity of the diagnosis tests classically used led to the development of
      molecular tools. PCR amplification of parasite specific sequences has
      considerably improved the diagnostic of the parasitic infection, the stage
      diagnosis as well as the post-therapeutic follow-up. But there are limits with a
      use in routine and research is still necessary to make PCR a real tool for
      control of sleeping sickness.

PMID- 15461964
TI  - [Envelope capture by retroviruses].
AB  - Retroelement transposition is a major source of diversity in genome evolution.
      Among the retrotransposable elements, the retroviruses are distinct in that their
      "transposition" extends from their initial host cells to neighboring cells and
      organisms. A determining step in the conversion of a retrotransposable element
      into an infectious retrovirus is the acquisition of an envelope glycoprotein,
      designated Env. Here, we review some examples of envelope "capture" by mammal
      retroviruses and provide evidence for such a mechanism by HTLV. This phenomenon
      may explain the notable conservation of env genes observed between
      phylogenetically distant retroviruses. Elucidation of these recombination
      processes should help to clarify retroviral phylogeny, better understand
      retroviral pathogenesis, and may lead to the identification of new retroelements.

PMID- 15461965
TI  - [HIV drug resistance and optimization of antiviral treatment in resource-poor
      countries].
AB  - HIV drug resistance has been associated with treatment failure in Western
      countries but the lessons learned can be useful in optimization of highly active
      antiretroviral treatment (HAART) in resource-poor settings. There is a need to
      improve access to HAART in such regions, but appropriate strategies must be
      rapidly implemented, such as adapted programs to facilitate adherence to therapy,
      rational use of genotypic drug resistance monitoring in specific situations, and
      use of alternative treatment regimens. The implications of HIV genetic diversity
      must also be considered in management of drug resistance.

PMID- 15461966
TI  - [Applications of congenic strains in the mouse].
AB  - The sequencing of the human and the mouse genomes has shown that the chromosomes
      of these two species contain approximately 30,000 genes. The biological systems
      that can be studied in an individual or in a tissue result from complex
      interactions within this multitude of genes. Before describing these
      interactions, it is necessary to understand the function of each gene. In the
      mouse, congenic strains are developed to introduce a chromosomal segment in a
      given inbred genetic background. One can then compare the biological effects of
      different alleles at the same locus in the same genetic background or the effect
      of a given allele in different genetic backgrounds. One can also introduce into
      different congenic strains with the same genetic background genes which control a
      complex genetic trait, then combine these genes by appropriate crosses to study
      their interactions. Although the chromosomal segment transferred into a congenic
      strain usually contains up to several hundreds of genes, molecular markers can be
      used to reduce this number as well as the number of crosses required for the
      development of congenic strains.

PMID- 15461967
TI  - [MicroRNAs: a new class of gene expression regulators].
AB  - MicroRNAs (miRs) are small non coding RNA, about 21-25 nucleotides in length,
      that direct post transcriptional regulation of gene expression through
      interaction with homologous mRNAs. Hundreds miR genes have been identified in
      animals and 40 in plants. Many of them are conserved between related species, and
      in some cases across phyla. Two mechanisms for regulation of gene expression by
      miRs have been reported. As described for lin-4 and let-7 miR of C.elegans, miRs
      can inhibit translation, which seems to represent the major mode of regulation in
      animals, or can direct cleavage of target mRNAs, which seems to represent the
      major mode of regulation in plants.

PMID- 15461968
TI  - [Patched/Sonic Hedgehog pathway and basal cell carcinoma].
AB  - The recent discovery of the role of the Patched Sonic Hedgehog pathway in the
      physiopathogeny of BCC (basocellular carcinoma) and Gorlin's syndrome has greatly
      improved our knowledge on the mechanism of development of these tumors. For the
      first time, murine models have been developed allowing to further understand
      other molecular events implicated in such tumors as well as providing in vivo
      models to search for new curative or preventive therapeutical strategies which
      would be helpful to control CBC multiple forms, that are often disabling.

PMID- 15461969
TI  - [Amphibians as a model system for the investigation of respiratory control
      development].
AB  - Recent medical advances have made it possible for babies to survive premature
      birth at increasingly earlier developmental stages. This population requires
      costly and sophisticated medical care to address the problems associated with
      immaturity of the respiratory system. In addition to pulmonary complications,
      respiratory instability and apnea reflecting immaturity of the respiratory
      control system are major causes of hospitalization and morbidity in this highly
      vulnerable population. These medical concerns, combined with the curiosity of
      physiologists, have contributed to the expansion of research in respiratory
      neurobiology. While most researchers working in this field commonly use rodents
      as an animal model, recent research using in vitro brainstem preparation from
      bullfrogs (Rana catesbeiana) have revealed the technical advantages of this
      animal model, and shown that the basic principles underlying respiratory control
      and its ontogeny are very similar between these two groups of vertebrates. The
      present review highlights the recent advances in the area of research with a
      focus on intermittent (episodic) breathing and the role of serotonergic and
      GABAergic modulation of respiratory activity during development.

PMID- 15461970
TI  - [Bibliometric indicators realities, myth and prospective].
AB  - The impact factor of scientific reviews, calculated by the Institute for
      Scientific Information (ISI), is increasingly used to evaluate the performance of
      scientists and programmes. Bibliometric indicators, originally designed for other
      purposes than individual evaluation, are very useful tools provided their
      interpretation is not extrapolated beyond their limits of validity. Here we
      present a critical analysis of appropriate uses and misuses of bibliometric data
      based on case studies. We also outline anticipated consequences of new
      information technologies, such as electronic journals or open access schemes, on
      the mode of science production, evaluation and dissemination in biomedical
      sciences.

PMID- 15461971
TI  - [Scandinavian eugenics: Nordic historians provide new approaches].
AB  - Late disclosure of the large scale of sterilization practices in the Nordic
      countries created an outburst of scandal: did these policies rely on coercion? To
      what extent? Who in the end was responsible? Sterilization practices targeted
      underpriviledged people first. The mentally retarded and women were their first
      victims. Operations were very frequently determined by other people's
      manipulative or coercive influences. Should the blame be put on the Social
      Democrats in power throughout the period (except in Finland and Estonia)? Apart
      from Denmark, perhaps, local physicians and local services, more than
      governments, seemed to have strongly supported sterilization practices.
      Teetotalers and feminists shared responsibilities. How can one explain that
      eugenics finally declined? Based on a sound application of the Hardy-Weinberg
      law, the science of the eugenicists was correct. Was it politics? But uncovering
      of the Nazi crimes had only a very small impact on eugenics. Some authors
      underline the fact that the Nordic scientific institutions were particularly
      suited to liberal values. Others point to the devastating effect on eugenics once
      hereditarist psychiatry fell from favour in the middle of the sixties.

PMID- 15461972
TI  - [Prevention in France, 2004: first elements for reflection].
AB  - Prevention has been underdeveloped in the public health arena, at least in
      France. It is a complex discipline, relying both on strong scientific methodology
      as well as social and economical considerations, which may be sometimes a source
      of conflicts.

PMID- 15461974
TI  - [Genetic information and the risk of collective stigmatization. The case of the
      Saguenay-Lake St. John region (Quebec)].

PMID- 15461975
TI  - [Scientific research and therapeutic innovation: an ambition-sharing].

PMID- 15461973
TI  - [MAOB: a modifier gene in phenylketonuria?].
AB  - Phenylketonuria (PKU), the most frequent inborn error of metabolism (1/15,000
      live births), is an autosomal recessive condition caused by phenylalanine
      hydroxylase deficiency. Despite early and strict dietary control, some PKU
      children still exhibit behavioral and cognitive difficulties suggestive of a
      partly prenatal brain injury. The reported variability between the cognitive and
      clinical phenotypes within the same family raises the question of modifying genes
      in PKU. We suggest here that monoamine oxidase type B, MAOB, an enzyme degrading
      phenylethylamine, a very toxic metabolite of phenylalanine, could act as a
      modifying gene since a variant enzymatic activity of MAOB in PKU patients with
      similar phenylalanine levels would result in different phenylethylamine levels
      and different clinical outcomes. Finally the report of low MAOB, and consequently
      expectedly high phenylethylamine levels in neonates is consistent with a
      phenylethylamine-mediated brain injury possibly causing irreversible damages in
      PKU newborns prior to onset of the low protein diet.

PMID- 15461976
TI  - [The knowledge tree bear innovation fruit...].

PMID- 15461977
TI  - [Health translational research, a new paradigm].

PMID- 15461978
TI  - Endovascular repair of abdominal aortic aneurysm in a patient with renal
      transplant.
AB  - Patients with functioning renal transplant who develop abdominal aortic aneurysm
      can safely be treated with endovascular repair. Endovascular repair of aneurysm
      avoids renal ischemia associated with cross-clamping of aorta.

PMID- 15461979
TI  - Stenting of a spontaneous dissection of the superior mesenteric artery: a new
      therapeutic approach?
AB  - Spontaneous dissection of the superior mesenteric artery (SMA) is rare and has
      been reported only sporadically. Therapeutic options are either a surgical
      approach, which is the more frequently adopted, or a simple observation. We
      report a case of spontaneous dissection of the SMA with a review of the
      literature and present a new therapeutic approach.

PMID- 15461980
TI  - Stenting of the superior mesenteric artery as a preoperative treatment for total
      pancreatectomy.
AB  - The patient was 58-year-old male with mucinous cyst adenocarcinoma of the
      pancreas. Prior to total pancreatectomy, preoperative CT and angiography showed a
      high-grade arteriosclerotic stenosis of about 1.0 cm in length in the ostium of
      the superior mesenteric artery (SMA), as well as the development of collateral
      vessels in the area around the head of the pancreas. A stent was placed in the
      SMA stenosis to preserve intestinal blood flow in the SMA region after total
      pancreatectomy, which was performed 25 days after stent placement. The
      postoperative SMA blood flow was favorable, with no postoperative intestinal
      ischemia, and the patient had an uneventful postoperative course.

PMID- 15461981
TI  - Acute renal failure after uterine artery embolization.
AB  - Renal failure is a potential complication of any endovascular procedure using
      iodinated contrast, including uterine artery embolization (UAE). In this report
      we present a case of acute renal failure (ARF) following UAE performed as a
      treatment for uterine fibroids. The likely causes of ARF in this patient are
      explored and the possible etiologies of renal failure in patients undergoing UAE
      are reviewed.

PMID- 15461982
TI  - Ileocolic arteriovenous fistula with superior mesenteric vein aneurysm:
      endovascular treatment.
AB  - We report a case of a venous aneurysm secondary to an acquired ileocolic
      arteriovenous fistula in a 64-year-old woman with recurrent abdominal pain and
      history of appendectomy. The aneurysm was diagnosed by ultrasound and computed
      tomography. Angiography showed an arteriovenous fistula between ileocolic
      branches of the superior mesenteric artery and vein. This vascular abnormality
      was successfully treated with coil embolization.

PMID- 15461983
TI  - Dual balloon-occluded retrograde transvenous obliteration of gastric varix
      draining into the left adrenal vein and left inferior phrenic vein.
AB  - A 66-year-old woman with a gastric varix, draining into a dilated left adrenal
      vein and a left inferior phrenic vein, was treated with dual balloon-occluded
      retrograde transvenous obliteration (B-RTO). Under balloon occlusion of the left
      adrenal vein and the left inferior phrenic vein, retrograde injection of a
      sclerosant (5% ethanolamine oleate) into the gastric varix was performed. Two
      weeks later, disappearance of flow in the gastric varix was confirmed on
      endoscopic ultrasound examination.

PMID- 15461984
TI  - Clifford J. Woolf, M.B., B,Ch., Ph.D. Recipient of the 2004 Excellence in
      Research Award.

PMID- 15461985
TI  - Schizophrenia molecular pathway emerges.

PMID- 15461986
TI  - Joubert syndrome may provide clues about human evolution.

PMID- 15461987
TI  - Stem cells show promise as stroke therapy.

PMID- 15461988
TI  - Parkinson's disease: alpha-synuclein build-up explained.

PMID- 15461989
TI  - Mouse model provides support for amyloid-cascade hypothesis.

PMID- 15461990
TI  - Role of reticulon proteins in Alzheimer's disease.

PMID- 15461993
TI  - Traction splints in EMS.

PMID- 15461991
TI  - Understanding autism: parents relate.

PMID- 15461996
TI  - Eagle Creek report: results of the 2-day consensus retreat on leading
      controversies in EMS.

PMID- 15461995
TI  - Short- and long-term effects of a single bout of exercise on heart rate
      variability: comparison between constant and interval training exercises.
AB  - Heart rate variability (HRV) was assessed during the short- (within 1 h) and long
      (within 48 h) term recovery following a single bout of either constant (CST) or
      interval training (SWEET) exercise performed at the same total physical work [9.4
      (0.3) kJ kg(-1)]. R-R intervals, systolic (SAP) and diastolic (DAP) arterial
      pressures were recorded in supine and upright positions before and 1, 24 and 48 h
      after the termination of the exercises in ten male subjects [mean (SEM), age 24.6
      (0.6) years, height 177.2 (1.1) cm and body mass 68.5 (0.9) kg]. The parameters
      were also recorded in the supine position during the first 20 min following the
      end of the exercise. Spectral analysis parameters of HRV [total (TP), low- (LF),
      and high- (HF) frequency power, and LF/TP, HF/TP and LF/HF ratios] were
      determined over 5 min during each phase. Except for higher HF values in both
      supine and upright positions during the first hour following CST compared with
      SWEET, cardiovascular and HRV analysis responses were of the same magnitude after
      their termination. R-R intervals, TP, and HF/TP were significantly decreased
      while LF/TP and LF/HF were significantly increased during the early recovery,
      when compared with control values. This could be a response to the significant
      decrease in SAP and DAP at this time. Twenty-four and 48 h after the end of the
      exercise, HRV parameters were at the same levels as before exercises in the
      supine posture, but a persistent tachycardia continued to be observed in the
      upright posture, together with reduced TP values, showing that cardiovascular
      functions were still disturbed. The short-term HRV recovery seemed dependent on
      the type of exercise, contrary to the long-term recovery.

PMID- 15461997
TI  - Close up: Eagles explain the rationale for change. Interview by David LaCombe.

PMID- 15461999
TI  - International Society for Biomedical Research on Alcoholism, 12th World Congress
      on Biomedical Alcohol Research, September 29 - October 2, 2004,
      Heidelburg/Mannheim, Germany. Abstracts.

PMID- 15461998
TI  - Current & future direction for the resuscitation of cardiac arrest patients.

PMID- 15462000
TI  - Antiretroviral therapy; where are we going?

PMID- 15462001
TI  - Public health service recommendations for the treatment of AIDS.

PMID- 15462002
TI  - Opportunistic infections in the age of highly active antiretroviral therapy.

PMID- 15462004
TI  - Strategies for long-term patient management.

PMID- 15462003
TI  - Phenotypic and genotypic testing in clinical practice.

PMID- 15462005
TI  - Approaches to salvage therapy.

PMID- 15462006
TI  - Controversies in AIDS treatment. Proceedings from CME conference sponsored by
      Cornell University Medical College and the American Foundation for AIDS Research
      (AmFAR). November 8, 1997. Faculty roundtable discussion.

PMID- 15462007
TI  - Controversies in AIDS treatment. Proceedings from CME conference sponsored by
      Cornell University Medical College and the American Foundation for AIDS Research
      (AmFAR). November 8, 1997. Question and answer session.

PMID- 15462008
TI  - Abdominal presentation of Burkitt's lymphoma in an HIV-positive patient.
AB  - The incidence of non-Hodgkin's lymphoma (NHL) has greatly increased in the AIDS
      population. It has been estimated that 8% to 27% of newly diagnosed cases of NHL
      are related to AIDS. The vast majority are clinically aggressive B cell-derived
      lymphomas. AIDS-associated NHLs are classified according to their anatomic site
      of location into three classes: (1) systemic (both nodal as well as extranodal),
      (2) primary central nervous system, and (3) body cavity-based lymphomas. We
      present a case report of a patient with HIV infection who presented with
      abdominal pain and distension and was found to have an intraabdominal type of
      Burkitt's lymphoma. This case underlines the following points: 1. In the
      evaluation of acute abdominal disease in a patient with AIDS, both AIDS-related
      infections as well as malignancies should be sought in the differential
      diagnosis. 2. Computed tomographic scanning of the abdomen is the modality of
      choice for characterization of disease as well as direction of appropriate
      therapy. 3. AIDS-related NHL remains an important biologic model for
      investigating the development and progression of lymphomas in the immune
      deficient host. 4. With the improved survival of patients with AIDS secondary to
      better prevention and treatment of infections, there may be an increase in AIDS
      associated malignancies; therefore, further research pertaining to the
      development and characterization of therapy modalities of such malignant tumors
      is mandatory.

PMID- 15462009
TI  - HIV-AIDS case histories: diagnostic problems. Diagnosis: Pseudomonas aeruginosa
      pneumonia.

PMID- 15462010
TI  - The validity of clinical examination in adolescent spinal deformities.
AB  - STUDY DESIGN: retrospective study on the accuracy and reliability of two clinical
      tests for scoliosis in young patients. AIM: to evaluate the inter-observer
      reliability of three non-invasive clinical measurements: hump height (HH), axial
      trunk rotation (ATR), and distance of the spinous process from the plumb line
      (DP) in standing; to compare these results with the corresponding radiographic
      measurements, the Cobb angles (CA). POPULATION: 116 patients, 78 females and 38
      males; 410 examinations have been performed (144 patients with brace and 266
      without). METHODS: a database was created using the measurements of different
      clinical parameters obtained from two examiners that measured them independently
      and in the same conditions. The Cobb method has been used as a gold standard.
      RESULTS: our results show a very high inter-rater reliability for HH and ATR
      measurements. The DP shows a different inter-rater reliability for the thoracic
      (C7) and lumbar (L3) spine, in both cases lower than that in the frontal plane;
      the ICC of the thoracolumbar DP (D12) was very low. The correlation with the
      radiographic value was weak.

PMID- 15462011
TI  - [Curative effect of preservation of femoral neck in total hip arthroplasty].

PMID- 15462013
TI  - Influence of light polarization on dynamics of all-fiber Raman lasers:
      theoretical analysis.
AB  - Using Stokes-vectors formalism, we present a simple model describing steady and
      dynamic characteristics of all-fiber Raman lasers. This model allows us to
      describe experimental behaviors that are not yet understood in Raman lasers. In
      lasers made with standard fibers we show theoretically that weak birefringence
      and the optical Kerr effect lead to the emergence of unstable regimes similar to
      those recently observed in experiments [Opt. Lett. 28, 2464 (2003)]. However, the
      model shows that lasers made with polarization-maintaining fibers are always
      stable, as evidenced in experiments.

PMID- 15462014
TI  - Abstracts from the First Congress of the French Nutrition Society. November 17
      19, 2003. Clermont-Ferrand, France.

PMID- 15462016
TI  - Proceedings of a symposium on osteoarthritic joint pain held at the Novartis
      Foundation. July 1-3, 2003. London, United Kingdom.

PMID- 15462015
TI  - Abstracts from the 13th Annual Meeting of the Japanese Society of Clinical
      Neuropsychopharmacology. October 1-3, 2--3. Hirosaki, Japan.

PMID- 15462017
TI  - Proceedings of the XV Lancefield International Symposium on Streptococci and
      Streptococcal Diseases. October 6-11, 2002. Goa, India.

PMID- 15462018
TI  - Proceedings of the Joint Nutrition Symposium of the European Society of
      Veterinary and Comperative Nutrition, the European College of Veterinary and
      Comperative Nutrition, the American Academy of Veterinary Nutrition, the American
      College of Veterinary Nutrition, the European Zoo Nutrition Research Group, and
      the Comperative Nutrition Society. August 21-25, 2002. Antwerp, Belgium.

PMID- 15462019
TI  - The pathology of amniotic fluid, from diagnosis to therapy. Proceedings of a
      conference. Parma, Italy, 14-15 November 2003.

PMID- 15462021
TI  - [Consensus conference on the rationale for use of anti-inflammatory agents in
      otorhinolaryngology].

PMID- 15462020
TI  - Stop taking uncivil liberties with DNA.

PMID- 15462022
TI  - Microscopy and Microanalysis 2004. Savannah, Georgia, USA, August 1-5, 2004.
      Abstracts.

PMID- 15462023
TI  - Libertarian bioethics and religion: the case of H. Tristram Engelhardt, Jr.
AB  - This paper is a critique of certain moral perspectives that are found in the
      second edition of Engelhardt's Foundation of Bioethics. These views are spelled
      out in explicit detail in his second edition, and follow on the heels of a
      profound religious conversion. Engelhardt is an eminent bioethicist with strong
      religious convictions that overlay much of his writing. The author wishes to
      question some of the conclusions that Engelhardt reaches as they touch upon moral
      frameworks, pluralism, and a 'secular' bioethics.

PMID- 15462024
TI  - Research ethics committees: differences and moral judgement.
AB  - Many people argue that disagreements and inconsistencies between Research Ethics
      Committees are morally problematic and there has been much effort to 'harmonise'
      their judgements. Some inconsistencies are bad because they are due to
      irrationality, or carelessness, or the operation of conflicting interests, an so
      should be reduced or removed. Other inconsistencies, we argue, are not bad and
      should be left or even encouraged. In this paper we examine three arguments to
      reject the view that we should strive for complete consistency between
      committees. The first argument is that differences in judgement are not
      necessarily incompatible with ideas of justice for patients who are potential
      participants of research reviewed by different committees. We call this 'the
      justice argument.' The second argument is that such committees do not have access
      to a single moral truth, to which their judgement is supposed to correspond. We
      call this the 'moral pluralism argument.' The third argument is that the process
      of ethics committee review is also morally relevant and not solely the outcome.
      We call this the 'due process argument.' While we fall short of establishing
      exactly how much variation and on what substantive issues would ethical
      permissible, we show that it is largely inevitable and that a certain amount of
      variation could be seen as a desirable part of the institution of medical
      research.

PMID- 15462025
TI  - When hope makes us vulnerable: a discussion of patient-healthcare provider
      interactions in the context of hope.
AB  - When hope is discussed in bioethics' literature, it is most often in the context
      of 'false hopes' and/or how to maintain hope while breaking bad news to patients.
      Little or no time is generally devoted to the description of hope that supports
      these analyses. In this paper, I present a detailed description of hope, one
      designed primarily for the healthcare context. Noting that hope is an emotional
      attitude, four key aspects are explored. In particular, the function of
      imagination in hope is discussed in depth. Through an examination of the
      relationship between hope and vulnerability, I demonstrate how adequately
      describing hope can broaden the normative inquiry into the role of hope in
      healthcare. Three ways in which persons with hope can be vulnerable are
      illustrated, and the challenge of how healthcare providers can attend in moral
      ways to the hopes of patients is identified.

PMID- 15462026
TI  - Focus group interviews examining attitudes toward medical research among the
      Japanese: a qualitative study.
AB  - OBJECTIVES: the purpose of ths study is to explore laypersons' attitudes towards
      and experiences of medical research, and to compare them with those of physicians
      in Japan. Designs and Participants: fourteen Japanese adults from the general
      public and seven physicians participated in one of three focus interviews.
      SETTING: Osaka, Japan. RESULTS: trust and distrust in the physician by whom the
      participants were invited to participate in research played a considerable role
      in their decisions about participation. That the participants felt an obligation
      to participate was also expressed. The lay participants perceived medical
      research as something entirely outside of their world. A greater willingness to
      volunteer for research was expressed if there were direct benefits to themselves
      or their families. Research methods such as use of placebos, double blinds, and
      randomisations seemed to cause negative attitudes to medical research. All
      physicians were convinced of the need for medical research, including double
      blinded randomised control trials, and its significant role in medical progress.
      Most physicians thought that the greater awareness of the need for medical
      research in the community and a better understanding of the psychology of
      potential research participants were necessary and urgent. CONCLUSIONS: there is
      a good possibility that the lay public and medical professionals have sharply
      different beliefs about and attitudes towards every aspect of medical research.
      Building up a better and equal patient-doctor relationship based on trust is a
      key issue in medical research, and it is mandatory to fill the gap in perception
      regarding medical research between them through fully informed debates.

PMID- 15462027
TI  - Reproductive autonomy rights and genetic disenhancement: sidestepping the
      argument from backhanded benefit.
AB  - John Robertson has famously argued that the right to reproductive autonomy is
      exceedingly broad in scope. That is, as long as a particular reproductive
      preference such as having a deaf child is "determinative" of the decision to
      reproduce then such preferences fall under the protective rubric of reproductive
      autonomy rights. Importantly, the deafness in question does not constitute a harm
      to the child thereby wrought since unless the child could be born deaf he or she
      would otherwise never have existed--his or her prospective parents would simply
      have chosen to abort. As such, for this child, being born deaf counts as a
      benefit, albeit of the "backhanded" variety, since the only other practical
      alternative is nonexistence. In what follows, I want to investigate this argument
      in detail. The target of my investigation will be the possible future use of gene
      therapy technology to "disenhance" one's offspring. I intend to show that the
      apparently unlimited right to reproductive autonomy, that is, the right to choose
      both the quantity and qualities of future offspring, entailed by the argument
      from backhanded benefit can in fact be "sidestepped" through considering what
      sorts of reproductive practices we as a society ought to allow.

PMID- 15462028
TI  - Right to life, right to die and assisted suicide.
AB  - In 2002 Diane Pretty went to the European Court of Human Rights to gain a ruling
      about assisted suicide. In the course of this she argued that the right to life
      implied a right to die. This paper will consider, from an ethical rather than a
      legal point of view, how the right to life might imply (or not) a right to die,
      and whether this includes either a right that others shall help us die, or a
      right against non-interference if others are willing to help us. It does this by
      comparing the right to life to conceptions of property rights. This is not
      because I think human life is property, but because some of our ways of talking
      and thinking about our control over our own lives seem to be similar to our
      thoughts about our control over our own property. The right to life has
      traditionally been taken as a negative right, that is a right that others not
      deprive us of life. Pretty's argument, however, seems to be moving towards a
      positive right, not just to remain alive, but to be enabled in doing what we want
      to with our lives, and thus disposing of them if we so choose. The comparison
      with property rights suggests that the right to die only applies if our lives are
      ours absolutely, and may itself be modified by the suggestion that suicide harms
      all of us by devaluing human life in general.

PMID- 15462029
TI  - Integrating justice and care in animal ethics.
AB  - In this paper I argue that the standoff between justice and care approaches to
      animal ethics presents us with a false dilemma. We should take justice's focus on
      reasoning from principles, and care's use of sympathetic awareness, as two
      integrated deliberative capacities necessary for the consideration of arguments
      for extending moral concern to animals. Such an integrated approach rests on a
      plausible account of the psychology of moral deliberation. I develop my argument
      as follows. Section I summarizes the nature of the debate between justice and
      care approaches to animal ethics, focusing on Brian Luke's arguments against
      justice approaches. Section II provides pro-justice rebuttals to Luke's
      objections. These rebuttals, while largely successful against Luke's objections,
      do not account for the intuition that sympathy does play a central
      epistemological role in animal ethics. Section III explains how sympathy
      cognitively simulates the perspective of the other, and thus can play an
      epistemological role in animal ethics. I argue that the abilities to simulate the
      perspective of the other and to reason from moral principles can complement each
      other. In section IV, I argue that though it may not be desirable to use both
      sympathy and reasoning from principles in all moral deliberation, it is a
      desirable aim when offering, and considering, moral arguments for what I will
      term the "extensionist project" of extending over moral concern to animals. I
      make this idea plausible by elucidating the claim that arguments for this project
      are best thought of as second-order deliberations about our first-order
      deliberative life.

PMID- 15462030
TI  - The specificity of the structure of photosynthetic reaction centers, which makes
      them efficient in excitation trapping and conversion.

PMID- 15462031
TI  - Cohen and kinds: a response to Nathan Nobis.

PMID- 15462032
TI  - Subjective character of experience in medical ethics: a reply to Atkins.
AB  - In a recent issue of this Journal Kim Atkins argued that Thomas Nagel's argument
      regarding a bat's phenomenal experience is important for understanding the value
      placed on patient autonomy in medical ethics. In this reply to her paper, I
      demonstrate that Atkin's argument (a) is based on her misinterpretations of
      Nagel's argument, and (b) can be established without appealing to such a
      controversial assumption as that which she makes.

PMID- 15462033
TI  - Regulations, ethics, and research with children.

PMID- 15462034
TI  - Financial conflicts of interest and protection of human research subjects.

PMID- 15462035
TI  - Institution announces that only one health human subject died in research.

PMID- 15462036
TI  - Effect of film thickness on the retention index of nitro and cyano compounds.
      Interpretation of the logarithmic equation.
AB  - Recently, a minimum was observed on the temperature dependence of retention
      indices in case of polar solutes chromatographed on apolar stationary phases.
      Physical significance is attributed to the equation constants describing the
      minimum. The equation constants are explained using a thermodynamic and a kinetic
      approach. Statistical properties of the models for different film thicknesses are
      compared. Chemical potential for one methylene unit is calculated in different
      ways for various film thicknesses and compared with literature values. The
      activation enthalpy attributed to the solvation process decreases as the carbon
      atom number (molecular mass) of the compounds decreases. The activation
      enthalpies for cyanoalkanes are always higher than those for the respective
      nitroalkanes. The interpretation of the equation constants does not change if the
      film thickness of the stationary phase increases (it is varied). This fact
      eliminates adsorption on the surface of the column wall from the possible causes
      responsible for the minimum on the retention index versus temperature curve.

PMID- 15462037
TI  - Mammaglobin-based strategies for treatment of breast cancer.
AB  - Mammaglobin is a gene that is expressed almost exclusively in the normal breast
      epithelium and human breast cancer. It is a member of the secretoglobin gene
      family and forms a heterodimer with lipophilin B. We have focused on the tissue
      specificity of mammaglobin as a potential mechanism for the specific killing of
      breast cancer cells. By elucidating the promoter region of mammaglobin, we hope
      to utilize this site as a method for turning on the apoptosis inducer gene, Bax,
      in breast cancer cells. The Bax gene will only be expressed at levels necessary
      to induce apoptosis in mammaglobin positive cells. This would include > 80% of
      all breast cancers and some normal breast epithelium. This type of targeted
      killing could be conceptualized as a biochemical mastectomy, that is, genetic
      ablation of breast tumor cells and perhaps non-malignant breast epithelium while
      preserving the adipose and stromal components of the breast. Work is also being
      done to address the binding specificity of the secreted mamaglobin protein. There
      is early evidence that the mammaglobin heterodimer may in fact bind to breast and
      breast cancer cells. If this finding is validated, this creates the possibility
      that mammaglobin can be tagged with radioisotope or toxin, so that binding of the
      tagged-mammaglobin complex results in the specific killing of that breast cancer
      cell. Finally, mammaglobin is being explored as a target for immune-based
      interventions. In vitro studies have demonstrated that T cell-mediated immune
      responses can be induced against mammaglobin-derived peptides expressed by MHC
      molecules on tumor cells and antigen-presenting cells.

PMID- 15462038
TI  - Distributive justice and rural healthcare: a case for e-health.
AB  - People living in rural areas make up 20 percent of the U.S. population, but only
      9 percent of physicians practice there. This uneven distribution is significant
      because rural areas have higher percentages of people in poverty, elderly people,
      people lacking health insurance coverage, and people with chronic diseases. As a
      way of ameliorating these disparities, e-health initiatives are being
      implemented. But the rural e-health movement raises its own set of distributive
      justice concerns about the digital divide. Moreover, even if the digital divide
      is overcome, e-health services may be of an inferior quality compared to face-to
      face medical encounters. In this paper, I argue that before we can fully
      understand the distributive justice implications of e-health, we must first
      understand what distributive justice means. I argue that five elements--fairness,
      quality, accessibility, availability, and efficiency--constitute a general
      conception of justice and that all of these elements must be considered when
      evaluating e-health for rural health profession shortage areas. In doing so, it
      may be necessary to make important tradeoffs among these elements. I then examine
      the development of e-health programs in light of Rawls's principle of equal
      opportunity and Daniel's notion of species-typical functioning. I conclude that
      in the context of e-health, Rawls's principle should be expanded to include
      geography as a prima facie morally relevant criterion for allocating healthcare
      benefits. I also conclude that Daniel's notion of species-typical functioning
      provides grounds for thinking of health and some healthcare services as special
      goods.

PMID- 15462039
TI  - Psychiatry in pictures. Mania (artist unknown, 1837).

PMID- 15462040
TI  - History and personal observations of electrical cardioversion of atrial
      fibrillation.
AB  - Electrical cardioversion of atrial fibrillation was initially very controversial.
      The procedure was carefully developed by Bernard Lown and his associates who
      experimented first on animals and then on postoperative patients using a direct
      current technique designed to avoid the vulnerable period. Their results,
      published in 1963, were soon accepted, and the procedure became a major
      therapeutic advance in the treatment of heart disease.

PMID- 15462041
TI  - Lethal sex: conditions of disclosure in counseling sexually active clients with
      HIV.
AB  - Confidentiality in psychological counseling is necessary if clients are to feel
      comfortable in revealing their darkest secrets. But this bond of trust has its
      moral limits. These limits are crossed in some cases in which HIV positive
      clients are sexually active with unsuspecting third parties. Distinguishing
      between Type 1 and Type 2 cases, the author shows how he has used applied ethics
      in drafting and defending a model rule for the American Counseling Association's
      Code of Ethics that permits, and sometimes morally requires disclosure in the
      former cases, but not in the latter.

PMID- 15462042
TI  - Patenting genes: a fast and furious primer.
AB  - Patents have been issued in the United States for genes and gene sequences since
      1980. Patent protection has provided incentives to aggressively probe the genome
      of humans and non-humans alike in search of profitable applications. Yet it is
      not clear that patent protection should have been afforded to genes and gene
      sequences and it is increasingly clear that patent protection, as currently
      formulated, is not an appropriate means to realize the full benefits of genetic
      research. As we stand on the threshold of a genetically enhanced future, in which
      we shall have the power to consciously steer our evolution as a species, we need
      to carefully consider how to shape the benefits of genetic research and how to
      recognize and contain its detriments.

PMID- 15462043
TI  - "The least of these": a Christian moral appraisal of vital organ procurement from
      "brain-dead" patients.

PMID- 15462044
TI  - [Venous catheterization in oncology. Statement of professional methodology].

PMID- 15462045
TI  - Ethical concerns of American Evangelical Christians relative to genetic
      interventions and the Human Genome Project, 1974 to the present.

PMID- 15462046
TI  - Holy dying, assisted dying?: an Anglican perspective on physician-assisted
      suicide.

PMID- 15462047
TI  - Limited information technology for patient care in physician offices.
AB  - Evidence of physicians' use of information technology (IT) to support patient
      care has been sketchy and anecdotal to date. However, new findings from the
      Center for Studying Health System Change (HSC) show wide variation in information
      technology adoption across physician practices, particularly by physician
      practice size. In 2001, nearly 60 percent of physicians in traditional practice
      settings--primarily solo or relatively small group practices where the vast
      majority of Americans receive care--reported that their practice used information
      technology in no more than one of the five following clinical functions:
      obtaining treatment guidelines, exchanging clinical data with other physicians,
      accessing patient notes, generating treatment reminders for the physician's use
      and writing prescriptions. Highest levels of IT support for patient care were
      found in staff- and group-model health maintenance organization (HMO) practices,
      followed by medical school faculty practices and large group practices. Overall
      rates of information technology adoption may have increased since 2001, but the
      variation in IT adoption by practice setting is unlikely to have changed

PMID- 15462048
TI  - [Potentialities of magnetic resonance imaging in the complex of prenatal
      radiation diagnosis of fetal malformations].
AB  - The purpose of the study was to investigate the potentialities of magnetic
      resonance imaging (MRI) in the complex of prenatal radiation diagnosis of fetal
      malformations. Twenty-eight female patients with suspected fetal malformations
      were examined. Ultrasound study was supplemented by MRI according to a specially
      developed protocol. Various fetal CNS malformations were diagnosed. These
      included the Arnold-Chiari syndrome, the Dandy-Walker syndrome, occlusive
      hydrocephaly, lobular holoprosencephaly, porencephaly, diaphragmatic hernias,
      anomalies of the abdomen and retroperitoneal space, as well as anomalies of
      facial structures, including median clefts, and dacryocystocele. The use of MRI
      in the complex prenatal radiation diagnosis makes it possible to visualize fetal
      malformation more clearly, contributes to the more adequate prediction of the
      outcome of pregnancy and to the choice of a management policy for a female
      patient.

PMID- 15462049
TI  - [Temporal bone CT in the diagnosis of acquired diseases of the external auditory
      canal].
AB  - CT was used to examine 50 patients (100 temporal bones) aged 10 days to 60 years
      who had no signs of lesion of the external auditory canal (EAC) and 23 patients
      (27 temporal bones) aged 13 to 65 years who had clinical manifestations of
      acquired stenosis or obturation of the EAC. Polypositional CT of the temporal
      bone is the most informative technique of visualization of the osseous part of
      the EAC, at the same time the anterior and posterior EAC walls were evaluated in
      the axial projection and the upper and lower EAC walls were assessed in the
      coronary projection. According to CT data, formation of the osseous part of the
      EAC occurs within the first 7 years of a child's life. In the presence of EAC
      changes, CT may assess their pattern (a soft tissue or osseous one), their
      magnitude and location along the walls of the canal, the tympanic membrane, and
      other structures of the temporal bone. CT reveals the causes of acquired EAC
      obturation, stenosis, and atresia: osteocartilaginous exostoses, osteomas, polyps
      of the EAC, tumors of the temporal bone, as well as obturative keratosis and
      posttraumatic stenosis of the EAC. The detected EAC changes determine further
      management policy in a patient.

PMID- 15462050
TI  - [Potentialities of temporal bone CT in the diagnosis of chronic purulent otitis
      media and its complications].
AB  - Temporal bone CT was used to examine a group of 87 patients with chronic purulent
      otitis media (103 temporal bones). The patients' age ranged from 2 to 74 years. A
      scheme was developed and proposed to evaluate the temporal bone by CT. The CT
      signs of chronic purulent otitis media uncomplicated by cholesteatoma and those
      of cholesteatomic purulent otitis were identified. The CT symptomatology of
      chronic purulent otitis includes: sclerotic changes in the bone tissue of the
      mastoid process, impaired pneumatization of the cavities of the middle ear,
      including the tympanic cavity, destructive changes in auditory ossicles, carious
      changes in the walls of the cavities of the middle ear. The CT semiotics of
      cholesteatoma depends on its site and spread into the temporal bone and includes
      as follows: deformation of the epitympanum due to soft tissue mass-induced
      destruction of the lateral wall; the dilated entrance into the antrum; the
      presence of a cavity with the sclerosed walls in the antromastoid area; carious
      changes in the auditory ossicles; the displacement of a chain of ossicles
      medially or laterally in relation to the initial site of cholesteatoma. CT
      reflects carious changes in the walls of the cavities of the middle ear,
      including the roof and labyrinthine wall of the tympanum, which allows
      labyrinthine fistula and intracranial cholesteatomic complications. The study of
      the temporal bone by the proposed scheme may reveal anomalies and the specific
      features of its structure: the presentation of the sigmoid sinus, the high
      elevation of the bulb of the jugular vein, diverticulum of the latter, the low
      standing of the bottom of the ACH.

PMID- 15462051
TI  - [Current approaches to estimating the sizes of the thyroid in neonates and
      infants from ultrasonographic data].
AB  - The thyroid was ultrasonographically studied in 384 pre-term babies aged 4-8 days
      of life. The sizes of thyroid lobes were determined; the echogenicity of the
      thyroid was compared with that of the parotid salivary gland. The infants were
      born by apparently healthy mothers and females with iodine deficiency. An
      original procedure for neonatal ultrasound study was developed. Data statistical
      processing yielded a formula of the individual standard of a thyroid volume,
      which allows neonatal goiter and thyroid hypoplasia to be established at early
      stages of life.

PMID- 15462052
TI  - [Complex radiation diagnosis of nephroptosis in children].
AB  - This paper analyzes a comprehensive study of 45 children treated at the Unit of
      Urology, Children's Republican Clinical Hospital One, Ministry of Health of the
      Russian Federation. Twenty children operated on for second- and third-degree
      nephroptosis made up an individual group. Clinical, laboratory, and radiation
      studies were performed 8-25 years after surgical treatment, by using radiation
      diagnostic techniques, such as excretory urography, ultrasonography, dynamic
      scintigraphy, aortography, Doppler color mapping ultrasonography. The authors
      have analyzed the capacities of complex radiation diagnosis of orthostatic renal
      dysfunctions in children with nephroptosis and the long-term results of
      nephropexy.

PMID- 15462054
TI  - [Evaluation of renal blood flow by Doppler study in children and adolescents with
      type 1 diabetes].
AB  - Renal blood flow was ultrasonographically studied in 220 children, adolescents,
      and young, postpubertal patients who had fell ill with type 1 diabetes mellitus
      (DM) in childhood (of them there were 111 (49.8%) males and 112 (50.2%) females
      with a disease history of 1 to 27 years (73 patients with diabetic nephropathy
      (DN) and 150 without DN). Thirty apparently healthy children and adolescents made
      up a comparison group. Doppler duplex scanning and Doppler pulse-wave study
      (DPWS) were made at the level of the great renal artery, segmental, interlobar,
      and arcuate arteries. With DPWS, the values of peripheral resistance were lower
      than the normal values at the level of interlobar and arcuate arteries in all
      patients with microangiopathies. There were significant differences between the
      groups of patients with different types of microangiopathies, the group of
      patients with DM without DMA, and the control group. Echography was used to
      determine the volumes of the kidneys in 220 patients. In patients with DM, renal
      volume was significantly greater than that in the control patients (p<0.05).

PMID- 15462053
TI  - [X-ray control of the kidneys and their development in the long-term period after
      surgical correction of hydronephrosis in children].
AB  - After surgical correction of hydronephrosis, the development of the kidneys was
      studied in 40 patients (44 hydronephroses) operated on at the age of 8 months to
      12 years. Postoperative follow-ups lasted at least 10 and 25 years. X-ray
      planimetric studies made it possible to quantitatively characterize the growth of
      the kidney, the increase or decrease in its parenchymal area, the appearance or
      progression of prior nephrosclerosis. X-ray studies could yield an objective
      assessment of the trend in renal development. By supplementing the data of
      excretory urography, radiological techniques and ultrasonography provided
      additional data on the kidney and its parenchyma. Analysis of the results of the
      X-ray planimetric studies have indicated that 28 patients (32 kidneys) had a
      uniform increase in the areas of the kidney and its parenchyma by 50-100%; in 9
      patients, the parenchyma increased by 2.5-4 times, the area of the kidney became
      only 50-100% larger. There was progression of nephrosclerosis with a 3-10%
      decrease in the area of parenchyma along with a 24-80% growth of the organ only
      in 3 cases after a quite satisfactory growth in the organ. These data show it
      necessary to perform long-term follow-ups of patients under the control of X-ray
      study as the most objective radiation diagnostic technique.

PMID- 15462055
TI  - [X-ray diagnosis of the causes of chronic constipation in children].
AB  - The genesis of chronic constipation in children remains the subject of discussion
      so far. A programme for examining patients with this condition has not been fully
      developed. X-ray studies of more than 300 children with chronic constipation from
      different age groups established that colonoproctodefecography was the most
      informative technique. The authors revealed that intestinal transit suffered
      slightly impaired and the cause of chronic constipation was impaired defecation
      due to the asynergy of the structures of the pelvic bottom. Dysfunction of the
      muscular structures of the pelvic diaphragm manifested itself as three main
      variants and their combinations.

PMID- 15462056
TI  - [New methods of X-ray surgical diagnosis and treatment of varicocele in children
      and adolescents].
AB  - The authors studied 520 patients with left-sided varicocele by left-sided
      phleborenotesticulography of Doppler ultrasonography, tensiometry of the left
      renotesticular venous system, blood gas composition, hormonal parameters, and
      etc. They present rationale for and evidence illustrations of aortomesenteric
      compression of the left renal vein, left-sided phleborenal hypertension prior to
      and after surgery for endovascular occlusion of the left testicular vein, before
      and following intervenous proximal testiculoiliac venous bypass surgery. The data
      of andrological dysfunction in patients with varicosis of the pampiniform plexus
      and spermatic cord (varicocele) are presented. An algorithm of examination and
      treatment of this cohort of patients, by using both miniinvasive techniques (for
      X-ray endovascular occlusion of the temporal veins under local anesthesia) and
      high tech operations using microsurgical techniques (testiculoiliac venous
      anastomosis), is outlined.

PMID- 15462057
TI  - [Magnetic resonance characteristics of minor focal cortical dysplasia in
      children].
AB  - The paper presents data on rare "obscure" forms of cortical dysplasias that play,
      nevertheless, an important role in the genesis of epilepsy in children.
      Pseudoschizencephalic phenomena of cortical organization (the straightened
      sulcus) and two dismigration defects (annular convolution and local
      simplifications of the pattern of sulci) are characterized. General information
      on the essence of this problem in Russian and foreign publications is presented.

PMID- 15462058
TI  - [Computed tomography of the nose and its accessory sinuses in the diagnosis of
      atresia of choanae].

PMID- 15462059
TI  - [Neuroradiological characteristics of pontocerebellar dysplasia or a type of
      Joubert's syndrome].

PMID- 15462060
TI  - [Facial skull bone malformations in children].

PMID- 15462061
TI  - History of burn medicine.

PMID- 15462062
TI  - Nutrition in patients with burn injuries in the intensive care unit.
AB  - Authors discuss the choices of nutritional support in patient after severe burn
      injury during the last three decades. Severe burn injury presents one of the most
      critical states of starvation under a severe stress to the organism. Timely and
      appropriate metabolic intervention can positively influence the hypermetabolism,
      which is a common reaction after an injury. Burn injury causes a long-term
      reaction with a great risk of multiple organ dysfunction (requirement to perform
      repeated dressing changes under general anesthesia, repeated surgeries, and
      infections). Incorporation of a nutritional support is based on the knowledge of
      pathophysiology and metabolic response to injury, and is influenced by choice of
      nutrition substrates and by possibility of its administration.

PMID- 15462063
TI  - Care for children after burn injury.
AB  - Authors are summing up basic approach in the treatment of severe burn injury in
      children. Thorough evaluation of severity of the injury is essential and
      determines further therapy. In this phase connection between care prior to
      hospitalization and in hospital is important. During the course of therapy in
      hospital, interdisciplinary teamwork is essential for the solution of various
      complications after burn injury. Important part of the care is cooperation with
      family of the child.

PMID- 15462064
TI  - Inhalation trauma in burns, cytology and biochemical findings.
AB  - We have followed in a pilot study a group of patients for cytological and
      biochemical changes of lavage in the upper and lower respiratory system. Into the
      study patients with respiratory burns confirmed by bronchoscopy and skiagraphy
      were included. We divided patients according to the Lung Injury Scores (LIS). We
      obtained the values in our sample group between intubation and last swab (before
      extubation). Listed are the risk factors, probability of survival, and lung
      histology results are listed for patients who died.

PMID- 15462065
TI  - Bacteriological monitoring after burn injury.
AB  - The most frequent and serious complication after burn injury is infection.
      Bacteriological monitoring of patients after burn injury is part of complex care.
      The algorithm of bacteriological checkups is set. Burned areas are
      microbiologically monitored by semi quantitative imprint method. Colonization is
      proportional to the length of patient's hospital stay. Resistance of the bacteria
      to antibiotics is usually higher in burn units than in other departments. That is
      why it is important to consider antibiotic treatment and strictly observe
      sensitivity by obtaining bacteriological results and current epidemiological
      situation. Burned patients are in danger of infection from the burned areas,
      respiratory tract, urinary tract and central venous catheters. Attending doctor
      should daily be in contact with the bacteriological laboratory.

PMID- 15462066
TI  - The role of skin bank in the treatment of severely burnt patients.
AB  - The accessibility of suitable temporary covers plays the key role in the
      treatment of severe skin losses. Biological covers have got the longest tradition
      in the wound healing. Skin banks are engaged in their production and
      distribution. Already in 1973 J. Moserova developed the methodology of harvesting
      pig xenografts. Later on, the short-term and the long-term method of storage were
      verified (Bohm, Konickova, Vogtova). In 1986, the Skin Bank in the Prague Burn
      Centre was established. In Prague Burn Centre the allografts are used very
      rarely, usually from the living donors, family members of the patients.
      Therefore, in our bank, we specialized in harvesting porcine xenografts. They are
      produced in three different forms--fresh, deep frozen in vapours of liquid
      nitrogen, and glycerolized. Porcine xenografts serve as a biological cover; they
      make barrier against infection and evaporation and protect the wound against
      desiccation. They are used namely for the treatment of superficial burn wounds,
      as a temporary coverage of excised wounds and as a dressing on release incision.
      Every year more than 10,000 strips have been used in our Burn Centre, it
      represents the area 200 m2. Since 1991 cultivation laboratory has been a part of
      our Skin Bank. We are interested in cultivation of human epidermal cells-
      keratinocytes. Cultured epidermal grafts became the first human in vitro prepared
      tissue, which was successfully transplanted to the patient. For the treatment of
      deep dermal skin losses we use either autologous keratinocytes, which can create
      permanent cover, or allogeneic cells, which stimulate spontaneous healing.
      Cultured keratinocytes are used in the treatment of burnt patients as well as in
      the trophic defects.

PMID- 15462067
TI  - The relation between emergency and burn medicine.
AB  - Emergency Medicine (EM) has evolved since 1950s--in the Czech Republic as well as
      abroad--from Anaesthesiology and Resuscitation in parallel with the Burn Medicine
      which has separated from Plastic Surgery. EM creates a link between the laymen
      first aid and the specialized hospital care, which is realized by the Emergency
      Medical Service (EMS). The EMS interventions for serious burn patients comprise
      the early professional prehospital medical care: establishing free airway and
      breathing, establishing intravenous/intraosseous access into the blood
      circulation, early shock therapy, early pharmacotherapy and analgesia, aseptic
      covering of damaged body surface, releasing escharotomies of circumferential
      burns of the chest and neck and optimal transport of patients into burn centres.

PMID- 15462068
TI  - The medical mission in NATO operations.
AB  - Medical support during crisis response operations should follow state-of-the-art
      standards of medicine, but at the same time to take into account more difficult
      conditions for medical care providing. The results of treatment of patients
      during crisis response operations should lead to results as close as possible to
      peacetime treatment. Multinationality has been working well in the Sipovo
      Multinational Integrated Medical Unit (MIMU) in Bosnia and Herzegovina until now.
      The mutual co-operation of nations results in a reduction in terms of personnel
      and material for all participants. It allows efficient use of resources and could
      be a model for Role 3 care in other hospitals. It has proven to be greater than
      the sum of its parts. The MIMU concept can be considered a cornerstone that
      guarantees the required continuity and stability.

PMID- 15462069
TI  - Inherited ichthyosiform dermatoses in childhood.

PMID- 15462070
TI  - Adenosine diphosphate ribose pyrophosphohydrolase in human skin.
AB  - Adenosine diphosphate ribose (ADPR) pyrophosphohydrolase (ADPR-PPase), which
      catalyzes the hydrolysis of ADPR to yield adenosine monophosphate (AMP) and
      ribose-5'-phosphate, was assayed in human penile foreskin. Since ADPR is formed
      from nicotinamide adenine dinucleotide (NAD) by NAD glycohydrolase (NADase),
      NADase was also assayed in human skin. The skin tissue obtained by circumcision
      was separated into three layers; epidermis of the outer prepuce, epidermis of the
      inner prepuce, and dermis. ADPR-PPase was found to be present in all of the three
      layers with nearly equal activity. NADase was also present in the epidermis of
      both the outer and inner prepuce, being about two times higher in the latter, but
      no activity was found in the dermis. When expressed in units of the same specific
      activity; i.e., micromoles product formed per hour per mg protein, the ADPR-PPase
      of human skin had two to five times greater activity than did NADase. The ADPR
      PPase of human skin was activated by Mg(+2), but inhibited by AMP and ATP. These
      results suggest that the breakdown of NAD occurs in human skin via ADPR to AMP
      and ribose-5'-phosphate by sequential action of NADase and ADPR-PPase.

PMID- 15462071
TI  - Nevoid basal cell epithelioma syndrome in Japan.
AB  - A 49-year-old Japanese man with typical features of nevoid basal cell epithelioma
      syndrome is reported. The patient had cystic lesions of the jaw bone, multiple
      basal cell epitheliomas of the scalp and face, pits on the palms and soles, bifid
      ribs, scoliosis and calcification of the falx cerebri. In Japan five certain
      cases have been reported previously. We added one new case and reviewed the other
      five cases briefly.

PMID- 15462072
TI  - Subcutaneous fat necrosis associated with pancreatitis and gastric carcinoma.
AB  - Subcutaneous fat necrosis associated with acute pancreatitis in a 54-year-old man
      was reported. The acute pancreatitis was proved histologically after gastrectomy
      for coincident early gastric carcinoma. The patient was successfully treated with
      prednisolone and his skin lesions subsided within a month.

PMID- 15462073
TI  - Pseudopyogenic granuloma: effects of corticosteroid on newly-formed vessels.
AB  - Papular lesions of pseudopyogenic granuloma were examined before and during
      treatment with systemic corticosteroid using both light and electron microscopy.
      Before treatment, these lesions showed a proliferation of vessels lined with
      plump endothelial cells and heavy lymphohistiocytic infiltrates with numerous
      eosinophils in the dermis. During treatment, flattened papules showed a
      dilatation of vessels lined with flattened endothelial cells, extravasation of
      red cells, discontinuity of endothelial basal lamina, and, ultimately,
      discontinuity of the endothelial cells themselves. Eosinophils were rarely found.
      From these findings, it can be said that the morphological effects of
      corticosteroid on microvasculature have in part been elucidated.

PMID- 15462074
TI  - Organ culture of adult human skin.
AB  - Proliferation and differentiation of the epidermis in organ culture of adult
      human skin by the sponge matrix method were studied histologically and
      autoradiographically, and the following results were obtained: 1) On the first
      day of culture, mitotic figures were already observable in the epidermis. The
      outgrowth of epidermal cells at the margins of the explants started. On the
      second day, there was transformation to a zone that will be referred to as the
      newly formed stratum corneum in the upper epidermis. 2) On the third and fourth
      days, the increased growth of epidermal cells caused thickening of the epidermis.
      Simultaneously, Malpighian cells progressively differentiated into a cornified
      layer. 3) On and after the fifth day, the basospinous cell layer was reduced in
      thickness in most of explants. On the ninth and tenth days, DNA synthesis in the
      basal layer was still obvious, although the epidermis showed a thickness of only
      one or two cells overlaid with a large number of horny layers. 4) In the culture
      medium supplemented with corticosteroid, the epidermal growth was slightly
      depressed with lessened formation of stratum corneum in the early stages of
      culture as compared with the explants cultured in the basic medium. The reduction
      of the basospinous layer was scarcely notable after the fifth day. Even after 10
      11 days, epidermal cells were well preserved and their stratified squamous
      architecture was less disorganized. It seemed that corticosteroid could prolong
      the survival of adult human skin in vitro. These findings indicate that this
      culture technique could be used as a model for organ culture of adult human skin.

PMID- 15462075
TI  - Incontinentia pigmenti achromians (Ito).
AB  - A patient with incontinentia pigmenti achromians was reported. She displayed
      other abnormalities such as a saddle nose, malformed auricles, growth
      retardation, convulsions and abnormal EEG. Histopathologically, a partial
      decrease in melanin granules in the basal layer and the presence of melanocytes
      which showed a weak dopa reaction were the main findings. The hypofunction of
      melanin production was detected by electron microscopy.

PMID- 15462076
TI  - Psoriatic arthritis: a clinico-radiological study.
AB  - A less documented entity of psoriatic arthritis was studied in 238 cases of
      psoriasis and it was detected in 5.1 % of cases. The prevalence of arthritis was
      found in the population over 40 years of age and was 2.7% of the males and 8.2%
      of the females. Psoriatic arthritis was much more common in females (male to
      female ratio = 1:2) in contrast to male predominance in psoriasis (male to female
      ratio = 1.6:1. Skin lesions usually precede the arthritis (50%); in others the
      onset is synchronous (41.7%) and in few of them the arthritis may come first
      (8.3%). Athritis is commonly encountered with moderate to severe involvement of
      skin (75%). In deforming type of arthritis the psoriasis was extensive and
      exfoliative (17%). The nails are more frequently involved at the onset of the
      arthritis. Rose-Waaler Test was negative in all of them. Anaemia (41.6%) and
      raised ESR (25%) was a feature in the active phase of the disease. Hyperurecaemia
      was noted in 41.6% of cases, indicating towards the extensive involvement of
      skin. The importance of radiological evaluation of spine, sterno-clavicular and
      sacro-iliac joints in all patients is stressed. Certain unusual features noted in
      the presented series of cases are; calcaneal spur (17%), spondylolisthesis (8.5%)
      and presence of LE cells (8.3%).

PMID- 15462077
TI  - Dermatological survey of onchocerciasis in Guatemala.
AB  - A comprehensive survey of onchocerciasis was performed on 1259 inhabitants in San
      Vicente Pacaya and the surrounding area. The total number of inhabitants examined
      was 1259, 763 males and 496 females. An examination of microfilarial density was
      carried out by the skin snip method. There were 610 microfilarial positives
      (50.4%) out of 1211 persons, 448 males (60.9%), and 162 females (34.1%). Nodules
      were examined by palpation, and there were 404 (32.8%) positives for nodule out
      of 1232 persons, 299 males (40.3%), and 105 females (21.4%). Eczematous
      dermatitis was seen in 149 persons, the generalized type in 13, and other types
      in 136. Depigmentation on the lower extremities was seen in 290 persons, the
      severity was graded from 0 to 4, and grade 1 depigmentation was seen in 91; grade
      2, in 143; grade 3, in 52 and grade 4 in 4 persons out of 1159 individuals
      examined. The positives for lymphadenopathy (above grade 2) were 464 (41.2%) out
      of 1127 individuals. Itching was seen in 129 (18.3%) of 705 individuals examined
      by the inquiry card method. The correlation between skin changes and
      onchocerciasis was also analyzed. Those individuals who were microfilarial
      positive in the skin snip and eyes, and who had palpable nodules were defined as
      being onchocerciasis patients. There was a high frequency of eczematous
      dermatitis, depigmentation on the lower extremities and lymphadenopathy in the
      onchocerciasis infected group, compared with the non-infected group, but there
      was no difference in the rate of itching between them. Hanging groin,
      elephantiasis and "erisipela de la costa" were not seen in this endemic area, and
      the degree of skin changes was slight, compared with that reported in Africa thus
      far.

PMID- 15462078
TI  - Psoriasis occuring in young monozygotic twins.
AB  - Psoriasis occuring in monozygotic twins is reported. Although these patients had
      a different living environment since birth the similarity in psoriatic pattern
      and its time of onset suggested the strong influence of genetic factors. However
      the major histocompatibility antigens A2, A11, Bw(16), found in these patients
      were not those, which have been reported to be significantly increased among
      Japanese psoriatics.

PMID- 15462079
TI  - Delayed hypersensitivity cross-reactions among Sporothrix species in
      sporotrichotic patients.
AB  - Cutaneous delayed hypersensitivity to antigens prepared from Sporothrix
      schenckii, S. schenckii var. luriei (atypical S. schenckii), S. curziconia, S.
      inflata and S. ghanensis was tested in eleven cutaneous sporotrichotic patients.
      Cross-reactions were observed in various degrees. Five normal controls were not
      reactive.

PMID- 15462080
TI  - Spectral sensitivity of ultraviolet photography.

PMID- 15462081
TI  - HLA haplotypes in affected siblings with leprosy.

PMID- 15462082
TI  - Turning chaos into opportunity.

PMID- 15462083
TI  - Plunket nurse proud to make a difference.

PMID- 15462084
TI  - Who is accountable for inadequate staffing?

PMID- 15462085
TI  - Canterbury nurse to stand for district health board.

PMID- 15462086
TI  - Nursing leaders must 'shout from the rooftops'.

PMID- 15462087
TI  - NZNO launches campaign for safe staffing ratios.

PMID- 15462088
TI  - Mereana Tangata--the first Maori registered nurse.

PMID- 15462089
TI  - Northland student pursues her dream.

PMID- 15462090
TI  - Nursing registration--a time to celebrate?

PMID- 15462091
TI  - Regulating New Zealand nurses.

PMID- 15462092
TI  - Centenary of registration celebrated in style.

PMID- 15462093
TI  - Preserving and valuing nursing history.

PMID- 15462094
TI  - The changing face of nursing registration.

PMID- 15462095
TI  - Meanings behind the nursing medal.

PMID- 15462096
TI  - Glimpses of history through Kai Tiaki's pages.

PMID- 15462097
TI  - Are double shifts and overtime professional practice?

PMID- 15462098
TI  - Urinary guanidinoacetic acid excretion as an indicator of gentamicin
      nephrotoxicity in rats.
AB  - The kidney is the main site of guanidinoacetic acid synthesis and excretion. The
      aim of this study was to examine whether urinary guanidinoacetic acid is a
      sensitive indicator for diagnosis of early-stage gentamicin nephrotoxicity. Early
      stage renal injury was induced in rats by a single intravenous injection of 5,
      10, or 30 mg/kg body weight gentamicin. Twenty-four hours after injection all
      rats were killed. Blood, urine and tissue guanidino compound concentrations were
      determined by high performance liquid chromatography. Glycine amidinotransferase
      activity in tissues was assayed according to the method of Pilsum. Urinary
      guanidinoacetic acid excretion was decreased in 5 mg/kg gentamicin-treated rats
      in comparison to that in control rats, whereas urine N-acetyl-beta-D
      glucosaminidase activity and beta2-microglobulin were unchanged. Guanidinoacetic
      acid concentration and glycine amidinotransferase activity in the kidney were
      significantly decreased in 5, 10, and 30 mg/kg gentamicin-treated rats; the
      decreases were dose-dependent. These results suggest that the urine
      guanidinoacetic acid concentration is a more sensitive indicator of renal injury
      than conventional indicators such as urine N-acetyl-beta-D-glucosaminidase and
      beta2-microglobulin.

PMID- 15462099
TI  - The influence of intravenous 1,25(OH)2D3 therapy on glucose metabolism in
      hemodialyzed patients with secondary hyperparathyroidism.
AB  - Glucose intolerance, insulin resistance and hyperinsulinemia are common findings
      in end-stage renal disease patients. Parathormone (PTH) and vitamin D3 are linked
      with disturbances of glucose metabolism. Glycated hemoglobin (HbA1c) reflects
      long-term glycemic control. HbA1c is a marker of increased risk of death in
      diabetic patients but also in general population. The aim of the study was to
      investigate the influence of 1,25(OH)2D3 therapy on long-term control of glycemia
      in hemodialyzed (HD) patients with severe secondary hyperparathyroidism (SHP).
      Eight HD patients with SHP (PTH=1088.6+/-472.2) were given intravenous
      1,25(OH)2D3 1-2 microg thrice a week, for 12 weeks (mean dose 4.5 microg/week).
      At baseline and after 12 weeks fasting blood was sampled for: glucose, insulin,
      HbA1c, PTH. Insulin/glucose ratio (I/G) was calculated as marker of insulin
      resistance. Results were compared with 14 healthy volunteers (controls) matched
      for age, sex and BMI. At baseline I/G was higher in HD vs controls 0.110+/-0.045
      vs 0.073+/-0.021 (p = 0.02), and of borderline significance at follow-up (0.106+/
      0.053, p=0.05 vs controls). PTH decreased significantly to 506.1+/-646.3 (p<0.02)
      during therapy. Significant decrease of HbA1c in HD patients was observed (5.84+/
      0.40 vs 5.13+/-0.51; p=0.01), while fasting glucose, insulin and I/G did not
      change significantly. Intravenous 1,25(OH)2D3 therapy is successful, even in
      patients with severe secondary hyperparathyroidism. Significant decrease in HbA1c
      with stable insulin concentration may indicate positive impact of intravenous
      1,25(OH)2D3 therapy on long-term glucose metabolism.

PMID- 15462100
TI  - Most common intoxication in nephrology ward organophosphate poisoning.
AB  - OBJECTIVES: In Taiwan, the widespread use of organophosphates (OPs) in
      agricultural and household environments results in numerous OP poisoning. To
      better understand the clinical significance of associated parameters on
      respiratory failure and patient outcome, we evaluate patients admitted to the
      Nephrology ward in our hospital with OP intoxication. PATIENTS AND METHODS: Over
      a period of 2 years, a total of 42 consecutive patients with OP poisoning
      admitted to the nephrology ward or the Intensive Care Unit of Chang-Gung Memorial
      Hospital were the subjects in the study. The diagnosis of poisoning was based on
      history of ingestion and characteristic clinical features of anticholinesterase
      agent poisoning. Prior to treatment, all symptoms recorded at emergency room and
      blood samples for blood chemistry including plasma amylase and plasma acetyl
      cholinesterase were collected from each patient immediately after the admission.
      RESULTS: As clinical manifestations of OP show, nausea and vomiting and
      salivation were the leading manifestations, 45.2% and 33.3%, respectively.
      Patients who developed respiratory failure were older than those who did not
      (54.3+/-6.9 vs. 43.1+/-5.6, p<0.05). The dosage of atropine administered for
      treatment was significantly higher in the patient group with respiratory failure
      compared to those without respiratory failure (29.7+/-14.5 vs. 9.1+/-10.2,
      p<0.05). Plasma amylase level of the patient group with respiratory failure was
      significantly higher than those without respiratory failure (436.1+/-87.1 vs.
      181.3+/-29.6, p<0.01). Of course, mean days of hospitalization in the respiratory
      failure group are significantly longer than the other group (12.1+/-2.1 vs. 5.4+/
      1.9, p<0.05). Based on univariant analysis, bradycardia, hypotension,
      fasciculation and coma were significant factors associated with respiratory
      failure. The dose of atropine administered for treatment was significantly higher
      in the oral exposure group compared to nonoral exposure group (23.6+/-12.6 vs.
      10.6+/-6.4, p<0.05). The same is true for the pralidoxime treatment (9.6+/-1.9
      vs. 5.3+/-1.4, p<0.05). As for mean days of hospitalization (11.6+/-3.9 vs. 6.4+/
      2.1, p<0.05) and fatality (2 vs. 0, p<0.05), those of oral exposure patients were
      significantly longer and higher than those with nonoral exposure. CONCLUSIONS: We
      demonstrate that elevated plasma amylase concentration was related to the
      development of respiratory failure in OP intoxication. It also provided us
      various important risk factors to identify those patients with OP poisoning who
      would ultimately require ventilatory support.

PMID- 15462101
TI  - Outcome prediction for critically ill children with acute renal failure requiring
      continuous hemofiltration.
AB  - Continuous hemofiltration has been used with increasing frequency for treating
      volume overload and acute renal failure in critically ill, hemodynamically
      unstable pediatric patients. This retrospective report investigates continuous
      hemofiltration in pediatric patients, and their survival rate. Sixty children
      treated between 1999 and 2001 with a diagnosis of acute renal failure and
      requiring continuous hemofiltration were admitted to this study to determine if
      pediatric risk of mortality III (PRISM III) scores were an accurate prediction of
      mortality. PRISM III scores were calculated on the day continuous hemofiltration
      commenced; mean PRISM III scores of non-survivors were significantly higher than
      mean scores of survivors. PRISM III scores may be a useful indicator of outcome
      in children receiving continuous hemofiltration.

PMID- 15462102
TI  - Expression of apoptosis-related proteins bcl-2 and bax along with transforming
      growth factor (TGF-beta1) in the kidney of patients with glomerulonephritides.
AB  - BACKGROUND: Apoptosis, a gene-directed form of cell death, has been involved in
      the resolution of renal injury but also in the development of scarring. Bcl-2 and
      bax are proteins related to apoptotic process that either provides a survival
      advantage to rapidly proliferating cells (bcl-2) or promote cell death by
      apoptosis (bax). Various cytokines and growth factors are involved in this
      process. This study investigates the expression of bcl-2 and bax and the presence
      of apoptotic bodies in relation to the TGF-beta1 expression at the time of
      diagnosis in the renal biopsies of patients with glomerulonephritis (GN).
      METHODS: Fifty patients with various types of GN and ten controls were included
      in the study. Bcl-2, bax and Transforming Growth Factor (TGF-beta1) positive
      cells were detected in kidney biopsies by immunohistochemistry, while apoptotic
      cells were detected by in situ end labeling of fragmented DNA (ISEL).
      Morphometric analysis was used for quantitation of immunostaining. RESULTS: The
      intensity of bcl-2, bax and TGF-beta1 immunostaining in the renal tissue of
      patients with GN was significantly more to the observed in the control biopsies.
      Bcl-2 and bax were expressed within the epithelial cells of proximal, distal and
      collecting tubules and in the renal interstitium. Bax and bcl-2 proteins were
      also identified within the glomeruli in a few patients but their distribution was
      not related to the type of GN. TGF-beta1 was expressed in the cytoplasm of
      tubular epithelial cells and to a lesser extent in the renal interstitium and
      glomeruli. A positive correlation of TGF-beta1 with the extent of bax
      immunostaining (r=0.498, p<0.05) and an inverse correlation with that of bcl-2
      (r= -0.490, p<0.05) were identified. Apoptotic bodies were identified only in the
      renal tissue of patients with GN and were mainly localized among tubular
      epithelial and interstitial cells. CONCLUSION: The intensity of bcl-2 and bax
      proteins expression and the presence of apoptotic bodies in the renal tissue of
      patients with GN suggest that apoptotic process is ongoing during the evolution
      of renal disease. The correlation of TGF-beta1 expression with that of apoptosis
      related proteins might represent an implication of this growth factor with
      apoptotic process in the human diseased kidney.

PMID- 15462103
TI  - Influence of hemodialysis procedure on HCV RNA detection in serum and peripheral
      blood mononuclear cells.
AB  - AIM: To assess whether hemodialysis procedure induces qualitative or quantitative
      changes in hepatitis C virus (HCV) RNA. METHODS: We obtained blood samples in the
      10 HCV RNA-positive patients of our hemodialysis unit before (sample I) and 5 min
      after a dialysis session (sample II), and before the next dialysis session
      (sample III). HCV RNA was tested by PCR in serum and peripheral blood mononuclear
      cells (PBMC). Serum viral load was measured by branched-DNA assay. RESULTS: Serum
      HCV RNA was positive in samples I, II and III of the 10 patients. PBMC HCV RNA
      was detected in samples I, II and III of seven patients. Mean viral load was
      1.43+/-0.99 Meq genome/mL in sample I, 0.86+/-0.40 Meq genome/mL in sample II and
      1.27+/-0.56 Meq genome/mL in sample III. CONCLUSIONS: HCV load was low in most
      HCV RNA-positive patients. It had a downward trend during dialysis procedure but
      HCV RNA remained detectable in all serum samples and in most PBMC samples.
      Therefore, qualitative HCV RNA seems to be better than viral load to assess HCV
      infection in hemodialysis patients.

PMID- 15462104
TI  - Pretransplant cardiac investigations in the Irish renal transplant population-
      the effectiveness of our current screening techniques in predicting cardiac
      events.
AB  - BACKGROUND: Coronary artery disease (CAD) is prevalent among endstage renal
      failure patients and remains the major cause of mortality following renal
      transplantation. Death with a functioning transplant institute remains the most
      common cause of kidney graft failure. In this study we attempt to evaluate the
      effectiveness of the clinical history and current screening techniques available
      in predicting posttransplant CAD and also assess the role of coronary angiography
      as a pretransplant screening technique. METHODS: Clinical data of 190 renal
      transplant patients was analyzed. Any clinical history of cardiac disease and all
      preoperative cardiac screening data was recorded for each patient. The study
      endpoints were the subsequent development of myocardial infarction (MI),
      undergoing coronary artery bypass graft (CABG) or death. RESULTS: Factors that
      were significantly associated with reaching a study endpoint included: age at
      transplant [Hazard Ratio (HR) 1.91, P<0.001], history of heart failure (HR 8.22,
      P<0.001), presence of CAD on coronary angiography (HR 5.55, P=0.033), anterior Q
      wave on electrocardiograph (ECG) (HR 8.6, P<0.001), carotid artery disease (HR
      3.74, P=0.030) and history of a cerebrovascular accident (HR of 4.32, P=0.008).
      The screening techniques of exercise stress testing and echocardiography were not
      conclusive as predictive variables of outcome. CONCLUSION: Clinical history and
      ECG results are good, practical and low-cost screening methods. In our study
      exercise stress testing and echocardiography were found to be of limited value.
      Coronary angiography is appropriate in certain high-risk groups but not necessary
      as part of screening in all potential renal transplant recipients.

PMID- 15462105
TI  - Effects of celecoxib on high-sensitivity C-reactive protein in chronic peritoneal
      dialysis patients.
AB  - To evaluate the effects of celecoxib, a cyclooxygenase-2 inhibitor, on the level
      of high-sensitivity C-reactive protein (hs-CRP), D-dimer, von Willebrand factor
      (vWF) and troponin-T, 46 chronic peritoneal dialysis (CPD) patients with hs-CRP
      equal or greater than 0.25 mg/dL were randomized to the treatment group who took
      200 mg of celecoxib daily for 4 weeks or to the control group who did not take
      the medication. The levels of hs-CRP, albumin, D-dimer, vWF and troponin-T were
      measured at baseline and at 4 weeks of the study. Baseline values of all the
      parameters were not significantly different between the two groups. In the
      control group, the levels of hs-CRP, albumin, D-dimer, vWF and troponin-T did not
      change. In the treatment group, administration of celecoxib for 4 weeks
      significantly reduced hs-CRP from median 0.77 (range 0.25-7.08) to 0.39 mg/dL
      (range 0.11-5.22, p<0.05). The levels of albumin, D-dimer, vWF and troponin-T
      levels were not affected by the administration of celecoxib. These results showed
      that celecoxib had an antiinflammatory effect in usual dosage in CPD patients.

PMID- 15462106
TI  - Does urinalysis predict acute renal failure after heart surgery?
AB  - Acute renal failure (ARF) usually develops in 5% to 30% of patients undergoing
      heart surgery and is associated with a more complicated clinical evolution course
      and with an excessive mortality of up to 80%. The objective of this study was to
      verify the frequency of ARF in postoperative coronary artery bypass surgery with
      and without cardiopulmonary bypass, by the evaluation of renal function markers'
      performance [plasma creatinine, plasma urea, urinalysis, fractional excretion of
      sodium, creatinine clearance and Alpha-glutathione S-transferase (alpha-GST)],
      besides to verify possible relations between clinical variables involved in
      postoperative heart surgery and the occurrence of renal insufficiency.

PMID- 15462107
TI  - Gabapentin versus levodopa for the treatment of Restless Legs Syndrome in
      hemodialysis patients: an open-label study.
AB  - BACKGROUND: Restless Legs Syndrome (RLS), a common problem increasing morbidity
      and mortality in hemodialysis (HD) patients, affects 20-30% of uremic patients.
      Our aim was to find the efficacy of gabapentin in the treatment of RLS in HD
      patients by comparing a largely used drug, levodopa. METHODS: Patients with RLS
      answered three questionnaires (RLS rating scale proposed by IRLSSG, the Short
      Form (SF)-36 and the Pittsburgh Sleep Quality Index) for the evaluation of
      severity of RLS, effects on quality of life and quality of sleep. RESULTS:
      Fifteen patients (4.7%) (5 F, 10 M) with a mean age of 45.8+/-15.3 years got RLS
      diagnosis. When we compare the two drugs for severity of RLS symptoms relief, the
      effect of gabapentin was more significant (p<0.001). Gabapentin significantly
      improved general health, body pain and social functions (p<0.001). Moreover,
      regarding sleep parameters, gabapentin was significantly superior to levodopa for
      sleep quality, sleep latency (p<0.001) and sleep disturbance (p<0.000).
      CONCLUSION: To our knowledge this was the first study comparing gabapentin and
      levodopa efficacy for the treatment of RLS in HD patients. Our results suggested
      that gabapentin is an effective drug for the management of RLS in hemodialysis
      patients.

PMID- 15462108
TI  - Comparative effects of fosinopril and irbesartan on hematopoiesis in essential
      hypertensives.
AB  - OBJECTIVE: To compare the response of erythropoiesis to an angiotensin receptor
      blocker, irbesartan with an angiotensin conversing enzyme inhibitor, fosinopril,
      in essential hypertensive patients with normal renal function. DESIGN AND
      METHODS: Thirty patients were randomized to receive either irbesartan (150 mg
      once daily) (n = 15, mean age 65.2+/-8.7 years) or fosinopril (20 mg once daily)
      (n = 15, mean age 57.4+/-11.5 years, difference is not significant) during 12
      weeks. Plasma erythropoietin, hemoglobin (Hb) and hematocrit (Hc) levels were
      measured at start and monthly after receiving the treatment. All values are
      expressed as mean+/-1SD. RESULTS: Irbesartan decreased erythropoietin levels
      (baseline 20.7+/-1.3 vs. 18.1+/-3.7 mU/mL, p=0.019), but they remained unchanged
      with fosinopril (baseline 18.8+/-1.3 vs. 18.6+/-1.6 mU/mL). Hb levels lowered in
      irbesartan group (baseline 13.8+/-1.2 vs. 13.5+/-1.1 g/dL, p=0.029), but they did
      not change in fosinopril-treated patients (baseline 14.6+/-1.3 vs. 14.5+/-1.3
      g/dL). Hc did not show any change neither in irbesartan group (baseline 40.9+/
      3.7 vs. 40.8+/-3.3 %) nor in fosinopril group (baseline 14.6+/-1.3 vs. 14.5+/-1.3
      %). CONCLUSIONS: Irbesartan lowered erythropoietin secretion and hemoglobin
      levels in essential hypertensives. Fosinopril can neither influence
      erythropoietin secretion nor decrease hemoglobin levels. Angiotensin receptor
      blockers seem to get higher efficacy for antagonism angiotensin effects. Safety
      of angiotensin receptor blockers in anemic hypertensive patients should be
      studied.

PMID- 15462109
TI  - Should the preservation of residual renal function cost volume overload and its
      consequence left ventricular hypertrophy in new hemodialysis patients?
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is an important predictor of
      mortality in dialysis patients. The loss of residual renal function (RRF) appears
      to occur more rapidly in hemodialysis than continuous ambulatory peritoneal
      dialysis (CAPD). It is more likely that volume expansion in patients on CAPD may
      preserve RRF. The aim of this study was to investigate whether there is a cause
      effect relationship between volume overload and preserving RRF in new
      hemodialysis patients. METHODS: Nineteen patients with end-stage renal disease
      (ESRD) starting hemodialysis therapy were included in the study. At the
      beginning, their elevated blood pressures (BP) were treated with antihypertensive
      drugs. Thereafter, until normovolemia and normal BP were obtained, strict volume
      control was applied. The effects of both treatment modalities on the loss of RRF
      and LVH were evaluated prospectively. RESULTS: At the initial examination, all of
      the patients were hypertensive and had markedly increased left ventricular mass
      index (LVMI). The daily urine production was 1575+/-281 mL. At the end of drug
      treatment period lasting three months, although BP significantly decreased, daily
      urine production and LVMI only decreased by 12% and 6%, respectively. At the end
      of the period in which strict volume control was applied, the body weight
      significantly decreased (from 60+/-5 to 55+/-8 kg, p<0.0001). This decrease in
      body weight was accompanied by marked decreases in dilated cardiac chamber size
      and more importantly daily urine production. At the end of this period, while 7
      of 19 patients had no residual urine production, residual urine production was
      below 200 mL/d in the remaining 12 patients. Although the period of volume
      control was short, there was significant reduction in the LVMI (decreased from
      251+/-59 to 161+/-25 gr/m2, p<0.0001). CONCLUSION: The results of our prospective
      study have clearly shown that the persistence of residual renal function in
      patients with ESRD starting hemodialysis therapy may largely depend on volume
      overload. Equally interesting was the finding that despite significantly reduced
      BP level with hypotensive drugs, there was no marked regression in LVMI. In the
      contrary, after the volume control period, LVMI was significantly decreased. Our
      results support the hypotheses that decrease in volume may be more important than
      pressure reduction in regressing the left ventricular hypertrophy.

PMID- 15462110
TI  - Safety and efficacy of fluvastatin in hyperlipidemic patients with chronic renal
      disease.
AB  - BACKGROUND: There are few reports on the safety and efficacy of long-term
      treatment with statins in patients with chronic renal disease and hyperlipidemia.
      We evaluated these subjects treated with fluvastatin. METHODS: After a 4-week run
      in period, a total of 80 patients with diabetic nephropathy or chronic
      glomerulonephritis were randomly allocated to receive dietary therapy and
      fluvastatin 20 mg/day (n=39), or dietary therapy alone (n=41) for a period of 48
      weeks. Lipid parameters, rhabdomyolysis-related indicators, 24-hour urinary
      albumin excretion and creatinine clearance were measured. The pharmacokinetics of
      fluvastatin was examined in 8 patients. RESULTS: Creatinine clearance and 24-hour
      urinary albumin excretion did not differ between the two groups. The peak serum
      fluvastatin concentration (Cmax) was 141+/-67 microg/L and the mean AUC0-6 h was
      341+/-149 microgh/L. Fluvastatin treatment significantly lowered serum total
      cholesterol, low-density lipoprotein (LDL) cholesterol and apo-lipoprotein B
      concentrations by 16%, 25%, and 22%, respectively, compared with patients
      receiving dietary therapy alone. There were no significant differences in serum
      triglyceride and high-density lipoprotein (HDL) cholesterol concentrations
      between the two treatment groups. Serum creatine kinase and aldolase
      concentrations did not change throughout treatment in both groups. CONCLUSIONS:
      Fluvastatin treatment significantly improved lipid parameters in patients with
      chronic renal disease. Fluvastatin was well tolerated, with no adverse effects on
      renal function and no muscular toxicity. However, the drug showed no direct
      renoprotective effects.

PMID- 15462111
TI  - Lactobacillus peritonitis: a rare cause of peritonitis in peritoneal dialysis
      patients.
AB  - Lactobacilli are part of the normal gastrointestinal and female genitourinary
      flora in humans and they are seldom pathogenic and rarely cause human disease. In
      the literature, Lactobacillus peritonitis was most common in immunocompromised
      patients, including patients under chronic peritoneal dialysis. We also suspect
      that the presence of Lactobacillus spp. in the peritoneal fluid might indicate
      the leakage of normal flora from a perforated intraabdominal hollow organ. To
      access the versatile clinical pictures of Lactobacillus peritonitis, this
      investigation retrospectively reviewed the medical records for Lactobacillus spp.
      isolated from peritoneal fluid from July 1998 to January 2002 at Chang-Gung
      Memorial Hospital, Taipei, Taiwan. A total of 10 patients were enrolled in the
      study. Six of these 10 patients had concomitant intraabdominal hollow organ
      perforation, and peritoneal fluid cultures in these six patients also contained
      bacteria other than Lactobacillus spp. All six patients had recently experienced
      either abdominal surgery or blunt abdominal trauma. The remaining four patients
      who had not undergone surgery had decompensated liver cirrhosis with ascites and
      spontaneous bacterial peritonitis. The results suggested that the presence of
      Lactobacillus spp. in the peritoneal fluid other than immunocompromised patients
      should raise the suspicion of hollow organ perforation in patients with recent
      abdominal surgery or blunt abdominal trauma.

PMID- 15462112
TI  - Association between activated renin angiotensin system and bone formation in
      hemodialysis patients: is the bone mass genetically determined by ACE gene
      polymorphism?
AB  - BACKGROUND: Angiotensin II (ang II) receptor subtype I binding sites has been
      recently demonstrated on bone cell precursors. Ang II stimulates DNA and collagen
      synthesis in human adult bone cells. The aim of this study is to evaluate the
      role of renin angiotensin system in the bone metabolism and to address the
      genetic influence of angiotensin converting enzyme (ACE) gene polymorphism on
      bone mass in hemodialysis patients. METHODS: Forty-eight end-stage renal disease
      patients (28 male, 20 female mean age 42+/-13 years,) on maintenance hemodialysis
      were included in the study. Bone mineral density (BMD) was estimated at lumbar
      spine and T score worse than -1.5 were considered as osteopenia. Serum
      parathyroid hormone (iPTH) and osteocalcin (OC), bone alkaline phosphatase (bAP)
      and carboxy terminal propeptide type 1 collagen (PICP) levels were measured as
      markers of bone metabolism. Plasma renin activity (PRA), serum ACE activity and
      ACE gene polymorphism (II, ID, DD) were determined. RESULTS: Bone mineral density
      and T score of the hemodialysis patients were 0.92+/-0.17 g/cm2 and -1.36+/-1.50,
      respectively. Twenty-one patients (43,7%) were osteopenic (T score worse than 
      1.5) and mean T score of osteopenic patients was -2.72+/-0.72. T score of
      nonosteopenic group was -0.29+/-0.99. Serum calcium, serum, phosphorus, serum OC,
      serum bAP, serum PCIP, serum PTH levels were similar in osteopenics and
      nonosteopenics. No difference was observed in predialysis PRA and in both pre-
      and postdialysis serum ACE activity of patients in both groups. PRA after
      hemodialysis in nonosteopenic group was higher than osteopenics (p<0.05). Percent
      increment in PRA in hemodialysis patients was correlated with T score (R=0.48 p
      <0.05). Serum ACE activity was positively correlated with serum iPTH (R=0.29,
      p=0.02), serum OC (R=0.35, p=0.01), serum bAP (R=0.34, p=0.01), serum PCIP
      (R=0.36, p=0.01). T score (-0.7+/-1.5, vs -1.7+/-1.3 p <0.05) was higher in DD
      group (n=19) compared to II+ID group (n=29). CONCLUSIONS: Association of
      biochemical and radiological signs of increased bone formation with activated RAS
      in hemodialysis patients might be an evidence for the involvement of this system
      in the regulation of bone metabolism.

PMID- 15462113
TI  - Ankle brachial index independently predicts early kidney disease.
AB  - INTRODUCTION: Chronic kidney disease (CKD) and atherosclerotic cardiovascular
      disease (CVD) are often both present in selected populations. The independent
      association of early renal disease and atherosclerosis has not been studied in
      the general population. We hypothesized that the presence of low ankle brachial
      index (ABI), a surrogate measure of atherosclerotic cardiovascular disease, is
      associated with a low estimated glomerular filtration rate (GFR). METHODS: The
      study population consisted of 14,917 middle-aged black and white men and women
      from the Atherosclerosis Risk in Communities (ARIC) Study. An ABI<0.90 was
      defined as the exposure, and an estimated GFR<90 mL/min/1.73 m2 was defined as
      the outcome. Logistic regression analysis was performed cross-sectionally using
      an ABI of 1.00-1.19 as the reference, and was adjusted for the usual
      cardiovascular risk factors. RESULTS: The presence of an ABI<0.90 was associated
      with an increased odds of having an estimated GFR<90 (OR: 1.80; 95% C.I.: 1.40
      2.32) compared to the reference group. After adjustment, an ABI<0.90 remained
      significant, and increased the odds of having an estimated GFR<90 (OR: 1.54; 95%
      C.I.: 1.17-2.04) compared to the reference group. The odds ratio for GFR<90 was
      higher among African Americans than Whites, 1.88 versus 1.36 respectively.
      DISCUSSION: This study gives support to the independent association of early CKD
      and atherosclerotic CVD. The relationship appears to be stronger among African
      Americans than among Whites. It will be necessary to investigate this observation
      more fully with prospective studies given the rising incidence of CKD.

PMID- 15462114
TI  - The role of myofibroblasts and interstitial fibrosis in the progression of
      membranous nephropathy.
AB  - Renal interstitial fibrosis has been observed in a large number of nephropathies
      and contributes to the progressive deterioration of renal function.
      Myofibroblasts have been implicated in the reparative process of tissue injury,
      including renal scarring secondary to glomerular diseases. We performed a
      retrospective study on 28 patients with biopsy-proven primary membranous
      nephropathy, to determine whether interstitial myofibroblasts and
      tubulointerstitial lesions correlated with renal function at follow-up.
      Tubulointerstitial pathology was evaluated by morphometric and semiquantitative
      methods. Interstitial myofibroblasts were counted; 24-hour urinary protein and
      serum creatinine at the time of diagnosis and at the end of follow-up were
      available for all the patients. There were 20 males and 8 females, age 2-67 years
      (mean 42.3+/-15.3), most of them with nephrotic syndrome (78.6%). The final renal
      function had deteriorated in 16 patients (57.1%) and in 5 patients (17.8%)
      reached end-stage. The renal outcome was correlated with histological changes. We
      found a positive correlation between the severity of tubulointerstitial damage
      and the deterioration of the final serum creatinine (r2=0.185; p=0.016).
      Myofibroblasts did not predict impaired renal function at the final follow-up.
      The current data do not support previous suggestions that myofibroblasts are a
      useful a predictor of end-stage renal disease.

PMID- 15462115
TI  - Treatment of severe IgA nephropathy with omega-3 fatty acids: the effect of a
      "very low dose" regimen.
AB  - BACKGROUND: The effect of a "very low dose" of purified omega-3 fatty acids (PFA)
      in the progression of severe IgA nephropathy (IgAN) was tested, in a randomized,
      prospective, controlled trial. METHODS: Fourteen patients were assigned to
      receive a "very low dose" of PFA (0.85 g EPA and 0.57 g PHA) and 14 patients were
      treated symptomatically and used as controls. Both groups were similar in terms
      of serum creatinine (Scr) and glomerular filtration rate (GFR) at baseline.
      Patients were treated for 4 years. The primary end-points were an increase of 50%
      or more in Scr or a decrease of 50% or more in GFR at the end of the study.
      RESULTS: During treatment, 1 patient (7%) in the PFA group and 6 (43%) in the
      control group had an increase of 50% or more in their Scr (p<0.01). Also, 1
      patient (7%) in the PFA group and 7 (50%) in the control group had a decrease of
      50% or more in GFR (p<0.007). The mean annual change in Scr was 0.2 mg/dL in the
      PFA group and 1.0 mg/dL in the control group (p<0.01). The mean annual change in
      GFR was -1.4 mL/min in the PFA group and -3.0 mL/min in the control group (p
      <0.001). One patient in the PFA group (7%) and 6 patients in the control group
      (43%) (p<0.01) developed end-stage renal disease during the period of
      observation. CONCLUSIONS: A "very low dose" of PFA is also effective in slowing
      renal progression in high-risk patients with IgAN and particularly those with
      advanced renal disease.

PMID- 15462116
TI  - Thyroid hormone transport is disturbed in erythrocytes from patients with chronic
      renal failure on hemodialysis.
AB  - AIMS: To now, there are no studies reporting whether thyroid hormones (THs)
      transport play a role in thyroid hormone dysfunction observed in chronic renal
      failure (CRF). Therefore, the aim of this study was to investigate the transport
      of THs in erythrocytes from patients with CRF on hemodialysis (HD). METHODS:
      [125I]-L-triiodothyronine ([125I]T3) and [125I]-L-thyroxine ([125I]T4)
      erythrocytes uptake was measured at 1 min and 5 min. To study L-triiodothyronine
      (LT3) and L-thyroxine (LT4) efflux from erythrocytes, we preloaded the cells
      during 180 min with [125I]T3 or [125I]T4 and measured their [125I]T3 or [125I]T4
      efflux during 60 min. RESULTS: [125I]T3 uptake in erythrocytes from uremic
      patients pre-HD was higher than control subjects by 50% at 1 min and by 55% at 5
      min. However, [125I]T4 uptake in erythrocytes from uremic patients was
      significantly lower at 1min (88%) and at 5 min (63%). LT3 efflux rate was lower
      and LT4 efflux was significantly higher than in control subjects. After 60-min of
      efflux, LT3 remained in erythrocytes was 80% higher and LT4 was 57% lower than in
      normal individuals. Neither [125I]T3 and [125I]T4 uptake, nor efflux rates were
      changed by hemodialysis. CONCLUSION: Despite the fact that uremic patients on
      hemodialysis show low serum levels of LT3, changes in LT3 influx and efflux could
      act as a compensatory mechanism that neutralize thyroid hormone dysfunction in
      order to maintain the euthyroid state.

PMID- 15462117
TI  - Plugging the gap--critical care skills are the current universal commodity.

PMID- 15462118
TI  - British Association of Critical Care Nurses position statement on the use of
      restraint in adult critical care units.
AB  - Critical care nurses in the United Kingdom have become increasingly concerned
      about the use, potential abuse and risks associated with physical restraint of
      patients. Restraint in critical care is not only confined to physical restraint
      but can also encompass chemical and psychological methods. There are concerns
      regarding the legal and ethical issues relating to the (ab)use of physical
      restraint techniques in critical care. The aim of this article was to present the
      British Association of Critical Care Nurses (BACCN) position statement on the use
      of restraint in adult critical care units and to provide supporting evidence to
      assist clinical staff in managing this process.

PMID- 15462119
TI  - A study exploring factors which influence the decision to commence nurse-led
      weaning.
AB  - Nurse-led weaning can improve patient outcome. Exploration of the factors that
      influence the commencement of weaning. Themes of decision-making,
      pathophysiological and multidisciplinary team factors emerged. Experience was a
      key factor in the decision to wean. The use of protocol-led weaning may not be
      useful in the decision to wean.

PMID- 15462120
TI  - The planning, organising and delivery of a memorial service in critical care.
AB  - The Intensive Care Society (1998) recommends that facilities should be available
      to follow up bereaved relatives. As part of bereavement follow up, a memorial
      service has been held at Royal Preston Hospital for the last three years. Over
      300 people attended in 2003. A memorial service is often referred to as a ritual.
      Rituals seem to meet certain universal needs, such as confirming the reality of
      the death, assisting in the expression of feelings, stimulating memories of the
      deceased and providing support to the family and friends of the deceased. An
      audit in 2003 has confirmed the value of the service: 97% of attendees were glad
      they attended the service and 72% would like to be invited to the service again
      next year.

PMID- 15462121
TI  - Learning portfolios--evidence of learning: an examination of students'
      perspectives.
AB  - There is a lack of evaluative literature on the use of learning portfolios in
      nursing. Many students are still unclear on the benefit of using a learning
      portfolio, and fulfilling the criteria for the portfolios remains low priority.
      Over a 5-year period, tutors on the Specialist Practitioner Qualification in
      Critical Care found that there was a wide variety of practice in portfolio use.
      There is comparatively little known about how the students perceive the use of
      portfolios. Therefore, a small descriptive survey took place in 2001/2002
      involving 22 previous students, to identify the value of portfolios from the
      student perspective. Recommendations from this study are given on how to improve
      portfolio use.

PMID- 15462122
TI  - Standardizing the assessment of clinical competence: an overview of intensive
      care course design.
AB  - Rationale for the development of the Certificate in Health Studies: Intensive
      Care and High Dependency for Adults course developed at Queens University
      Belfast, Northern Ireland. Structure and content of clinical module reviewed.
      Clinical assessment strategy discussed. Focus on the utilization of a
      standardized portfolio, individualized learning contract and objective structured
      clinical examination (OSCE) to evaluate clinical competence. Evaluation of OSCE
      as an assessment tool and of the course provision.

PMID- 15462123
TI  - Testing for B-type natriuretic peptide in the diagnosis and assessment of heart
      failure: what are the nuances?

PMID- 15462124
TI  - New guidelines on acute otitis media: an overview of their key principles for
      practice.

PMID- 15462125
TI  - From principles to practice: case-based applications of the acute otitis media
      guidelines.

PMID- 15462126
TI  - The microbiology of cocoa fermentation and its role in chocolate quality.
AB  - The first stage of chocolate production consists of a natural, seven-day
      microbial fermentation of the pectinaceous pulp surrounding beans of the tree
      Theobroma cacao. There is a microbial succession of a wide range of yeasts,
      lactic-acid, and acetic-acid bacteria during which high temperatures of up to 50
      degrees C and microbial products, such as ethanol, lactic acid, and acetic acid,
      kill the beans and cause production of flavor precursors. Over-fermentation leads
      to a rise in bacilli and filamentous fungi that can cause off-flavors. The
      physiological roles of the predominant micro-organisms are now reasonably well
      understood and the crucial importance of a well-ordered microbial succession in
      cocoa aroma has been established. It has been possible to use a synthetic
      microbial cocktail inoculum of just 5 species, including members of the 3
      principal groups, to mimic the natural fermentation process and yield good
      quality chocolate. Reduction of the amount of pectin by physical or mechanical
      means can also lead to an improved fermentation in reduced time and the juice can
      be used as a high-value byproduct. To improve the quality of the processed beans,
      more research is needed on pectinase production by yeasts, better depulping,
      fermenter design, and the use of starter cultures.

PMID- 15462127
TI  - Biopolymer-based antimicrobial packaging: a review.
AB  - The term antimicrobialpackaging encompasses any packaging technique(s) used to
      control microbial growth in a food product. These include packaging materials and
      edible films and coatings that contain antimicrobial agents and also techniques
      that modify the atmosphere within the package. In recent years, antimicrobial
      packaging has attracted much attention from the food industry because of the
      increase in consumer demand for minimally processed, preservative-free products.
      Reflecting this demand, the preservative agents must be applied to packaging in
      such away that only low levels of preservatives come into contact with the food.
      The film or coating technique is considered to be more effective, although more
      complicated to apply. New antimicrobial packaging materials are continually being
      developed. Many of them exploit natural agents to control common food-borne
      microorganisms. Current trends suggest that, in due course, packaging will
      generally incorporate antimicrobial agents, and the sealing systems will continue
      to improve. The focus of packaging in the past has been on the appearance, size,
      and integrity of the package. A greater emphasis on safety features associated
      with the addition of antimicrobial agents is perhaps the next area for
      development in packaging technology.

PMID- 15462128
TI  - Milk proteins for edible films and coatings.
AB  - Due to the recent increase in ecological consciousness, research has turned
      toward finding edible materials. Viable edible films and coatings have been
      produced using milk proteins. These films and coatings may retard moisture loss,
      are good oxygen barriers, show good tensile strength and moderate elongation, are
      flexible, and generally have no flavor or taste. Incorporation of lipids in
      protein films, either in an emulsion or as a coating, improve their properties as
      barriers to moisture vapor. Interactions between chemical, structural properties,
      as well as film-forming conditions and functional properties of edible milk films
      are elucidated. Some potential uses of milk protein packaging, which are hinged
      on film properties, are described with examples.

PMID- 15462129
TI  - Comprehensive study on vitamin C equivalent antioxidant capacity (VCEAC) of
      various polyphenolics in scavenging a free radical and its structural
      relationship.
AB  - Antioxidant capacity for a wide range of natural or synthetic polyphenolics was
      comprehensively evaluated by vitamin C equivalent antioxidant capacity (VCEAC)
      assay using free blue/green ABTS radicals. The polyphenolics tested are grouped
      into the following categories: vitamins (beta-carotene, alpha-tocopherol, vitamin
      A, and vitamin C), phenolic acids (benzoic acid, phenylacetic acid, cinnamic
      acid, and their derivatives), flavonoids (anthocyanidin, flavanol, chalcone,
      flavanone, flavone, flavonol, isoflavone, and their derivatives), synthetic food
      additives (BHA, BHT, TBHQ, and PG), and other miscellaneous polyphenolics
      (ellagic acid, sesamol, eugenol, thymol, etc.). A positive linear relationship
      between VCEAC and the number of free OH groups around the flavonoid framework was
      found, whereas, for phenolic acids, the linear relationship was not as good as
      with the flavonoid aglycones. Groups of chemicals having comparable structures
      generally showed similar trends. Polyphenolics commonly showed a higher VCEAC
      compared to monophenolics. Compounds like gallic acid with 3 vicinal hydroxy
      substitutions on the aromatic ring in phenolic acids or like epigallocatechin
      with 3 vicinal hydroxy substitutions on the B ring in flavonoids showed the
      highest antioxidant capcity among the groups. In the flavonoids, 2 characteristic
      chemical structures were very important, the catechol moiety in the B ring and
      the 3-OH functional group in a chroman ring. Glycosylated flavonoids showed less
      potent antioxidant capacity than their aglycone alone. Synthetic antioxidant food
      additives (BHA, TBHQ, and BHT) conventionally used in the food industry were less
      effective antioxidants than ascorbic acid. Other naturally occurring
      polyphenolics tested followed the expected general trends of phenolic acids and
      flavonoids.

PMID- 15462130
TI  - Antioxidants and prevention of chronic disease.
AB  - The generation of reactive oxygen species (ROS) and other free radicals (R)
      during metabolism is a necessary and normal process that ideally is compensated
      for by an elaborate endogenous antioxidant system. However, due to many
      environmental, lifestyle, and pathological situations, excess radicals can
      accumulate, resulting in oxidative stress. Oxidative stress has been related to
      cardiovascular disease, cancer, and other chronic diseases that account for a
      major portion of deaths today. Antioxidants are compounds that hinder the
      oxidative processes and thereby delay or prevent oxidative stress. This article
      examines the process of oxidative stress and the pathways by which it relates to
      many chronic diseases. We also discuss the role that endogenous and exogenous
      antioxidants may play in controlling oxidation and review the evidence of their
      roles in preventing disease.

PMID- 15462131
TI  - International trends in bioassay use for effluent management.
AB  - The use of effluent bioassays in various international jurisdictions is reviewed,
      resulting in an analysis of themes and trends in: regulatory use, different uses
      of bioassays in meeting protection goals, different types of bioassays, bioassay
      test variability, statistical design, use of effluent bioassays to predict
      receiving environment effects, and uptake of effluent bioassay testing by
      developing countries. Current effluent bioassay use by jurisdictions in North
      America, the European Union, and Asia/Pacific is described. The historical trend
      for many jurisdictions has been to start with chemical hazard-based systems, then
      add effluent bioassays (first lethal, then sublethal measures) and then use
      receiving environment evaluations to predict or measure impacts. For
      jurisdictions adopting effluent bioassays over the past decade, policies about
      the use of in vivo vertebrate tests appear to be influencing the types of
      bioassays that are used and there is also a trend towards micro-scale tests. In
      countries where regulations relating to effluent management do not require
      effluent bioassays, uptake of bioassays is relatively slow. Good practice for
      effluent bioassay applications can only be defined with regard to the regulatory
      regime, as differences between jurisdictions (e.g., hazard-based versus risk
      based regimes, policies on in vivo vertebrate testing) will result in different
      choices.

PMID- 15462132
TI  - A regulatory framework for controlling effluent discharges using toxicity testing
      in the UK.
AB  - Legislation designed to regulate effluent discharges is expressed in terms of
      minimising the risk of harm of that discharge to the environment. Practical
      implementation is usually based on the control and measurement of a limited
      number of individual chemicals. However, this is not always effective because of
      the complex nature of some discharges or the lack of data for some chemicals,
      preventing the definition of acceptable levels in the environment. Direct
      Toxicity Assessment (DTA) clearly has a role in such circumstances because it
      avoids the need for a comprehensive chemical characterisation of effluent
      discharges. Several scenarios in which DTA can play a useful role in water
      quality management under current legislation have been identified. A 'generic'
      framework for the implementation of bioassays for effluent control is proposed.
      This provides a number of options in terms of the level of environmental
      protection afforded and the 'starting point' for a DTA programme (i.e. whether it
      is based on local measurable impacts on water quality or directed from the outset
      towards the risk assessment of particular discharges). A DTA programme can be
      developed that meets both the technical and regulatory requirements of these
      different scenarios. Guidance on the design of such programmes for different
      scenarios is provided.

PMID- 15462133
TI  - Hazardous chemicals in complex mixtures--a role for direct toxicity assessment.
AB  - Whole sample toxicity assessment can help identify, diagnose and control impacts
      in the environment arising from the release of hazardous chemicals in complex
      mixtures. This role for direct toxicity assessment is considered against a
      background of increased international activity in the regulation of chemicals and
      reported improvements in the quality of surface waters in England and Wales.
      International legislation is largely focussed on the regulatory control of
      chemicals as individual substances although the majority of substances released
      to the environment enter in complex mixtures either as point source discharges or
      diffuse inputs. Whole sample measures of biological effect support the
      traditional substance by substance approach and provide a diagnostic capability
      to direct investigation into the likely chemicals or groups of chemicals of
      concern. Reported improvements in surface water quality in England and Wales are
      considered in the context of current impacts associated with hazardous
      substances.

PMID- 15462134
TI  - The use of direct toxicity assessment in the assessment and control of complex
      effluents in the UK: a demonstration programme.
AB  - This paper outlines the background, objectives, methodology, findings, outputs
      and recommendations from the Direct Toxicity Assessment (DTA) Demonstration
      Programme. This was a trial of a suite of bioassay methods and a seven-step
      protocol designed to deliver water quality improvements in catchments with well
      defined water quality problems, where ecotoxicity from effluents was a
      contributing factor. The trial was run as a collaborative venture between the
      environmental regulators and water and manufacturing industries in the UK and was
      conducted at three project sites: -a reach of the river Aire near the city of
      Bradford in Yorkshire; -a reach of the River Esk near the town of Langholm on the
      border between Scotland and England; and -the lower Tees estuary on the north
      east coast of England. The outcomes of each project are summarised in this paper.
      The learning points delivered by the programme were used to make recommendations
      to the regulators on how best to use bioassays for the assessment and control of
      complex effluents in the UK. Guidance was provided on how to carry out the
      bioassays and on how to use the data generated for regulatory decision-making.
      The programme also demonstrated how the regulators and the regulated can
      successfully work together to tackle environmental issues and deliver effective
      and workable solutions.

PMID- 15462135
TI  - Bioassay selection, experimental design and quality control/assurance for use in
      effluent assessment and control.
AB  - In the UK Direct Toxicity Assessment Programme, carried out in 1998-2000, a
      series of internationally recognised short-term toxicity test methods for algae,
      invertebrates and fishes, and rapid methods (ECLOX and Microtox) were used
      extensively. Abbreviated versions of conventional tests (algal growth inhibition
      tests, Daphnia magna immobilisation test and the oyster embryo-larval development
      test) were valuable for toxicity screening of effluent discharges and the
      identification of causes and sources of toxicity. Rapid methods based on
      chemiluminescence and bioluminescence were not generally useful in this
      programme, but may have a role where the rapid test has been shown to be an
      acceptable surrogate for a standardised test method. A range of quality assurance
      and control measures were identified. Requirements for quality control/assurance
      are most stringent when deriving data for characterising the toxic hazards of
      effluents and monitoring compliance against a toxicity reduction target. Lower
      quality control/assurance requirements can be applied to discharge screening and
      the identification of causes and sources of toxicity.

PMID- 15462136
TI  - Estimating spatial patterns of effluent exposure concentrations in direct
      toxicity assessment studies.
AB  - Hydrodynamic models of differing scale and complexity were used to estimate
      spatial patterns of effluent concentration in discharge plumes in the River Esk
      and the Lower Tees Estuary. The output from the Tees model was used, in
      conjunction with measurements of toxicity determined in short-term oyster embryo
      tests, to predict contours/zones of toxicity in the estuary associated with
      effluent discharges from four chemical processing sites. One of the discharges
      also combined the input from a municipal sewage treatment works. The models
      appeared to be effective in predicting patterns of dilution and dispersion of the
      effluent discharges in the respective receiving environments. Confirmation of the
      predictive capabilities of the Tees model was achieved by comparing predicted and
      measured toxicity in different regions of the plumes associated with the four
      discharges. Differences between predicted and measured toxicity for two of the
      four discharges were explicable in terms of failure to take account of the
      effects of real-time wind conditions when test samples were collected or overlap
      of adjacent discharge plumes. Suggested refinements to the models and measurement
      of effluent toxicity would further enhance the utility of this approach for
      determining the extent and significance of the effects of effluent discharges in
      receiving environments.

PMID- 15462137
TI  - Risk characterisation in direct toxicity assessment of the River Esk and the Tees
      Estuary.
AB  - This paper illustrates the use of deterministic and probabilistic approaches to
      the ecotoxicological risk assessment of effluents through two simple examples
      taken from the UK Direct Toxicity Assessment Demonstration Programme. In this
      study, the direct protection objective for the River Esk in Scotland was the
      prevention of short-term lethal toxicity to invertebrates from exposure to
      effluent containing insecticides. Both a deterministic and a probabilistic risk
      characterisation show that such toxicity is very unlikely to occur. The
      protection objectives for the Lower Tees Estuary were more complex, due to a
      variety of discharges and potentially sensitive species. A deterministic risk
      assessment using the most sensitive species suggests that toxicity will be high
      at all times. In contrast, a probabilistic risk assessment suggests that,
      although acute toxicity is considerable, it is not likely to occur at all times
      or affect all species, and discharge scenarios do exist in which acute toxicity
      could be relatively low. These two case studies illustrate the use of
      probabilistic risk assessment in achieving more realistic assessments of effluent
      toxicity through use of all available data.

PMID- 15462138
TI  - Toxicity reduction evaluation, toxicity identification evaluation and toxicity
      tracking in direct toxicity assessment.
AB  - Toxicity reduction evaluations (TREs) in the River Esk and Lower Tees Estuary
      were based on the approach described by USEPA, but adapted to tackle the specific
      problems of the two sites. A combination of toxicity tracking and toxicity
      identification evaluation (TIE) was used at both locations to enhance the
      understanding of source and type of toxicants present. The assessment of toxicity
      at Langholm focussed on pesticides present in the sewerage network. The TIE
      programme indicated that the most likely toxic agents within the effluent were
      the organophosphate pesticides diazinon and to lesser extent propetamphos,
      although these did not account for all of the observed toxicity. The exact source
      of these toxicants was not clear although toxicity tracking identified two
      potential candidates. The TRE undertaken on the discharge to the lower Tees
      utilised high-throughput methods with standard test organisms to generate
      toxicity information throughout a complex sewerage network. The toxicity tracking
      information was used in conjunction with TIEs to identify a number of key sources
      of toxicity. Substantial toxicity was associated with a currently untreated
      industrial effluent. Chemical analysis and TIE highlighted cyanide as the likely
      toxicant in this effluent and its possible significance in the final discharge.

PMID- 15462139
TI  - Managing complex mixtures of chemicals--a forward look from the regulators'
      perspective.
AB  - The key findings to emerge from the successful Direct Toxicity Assessment
      Demonstration Programme are reviewed. At present, whole sample toxicity tests can
      identify and help control releases of complex mixtures that are likely to cause
      short-term toxic effects. Protection of aquatic organisms from the many hazardous
      chemicals that enter the environment, usually as complex mixtures, will require
      the introduction of new and improved techniques that are affordable and provide
      rapid turnaround of information. A number of bioassays were rigorously tested
      during the DTA programme. Further developments are suggested and other methods,
      including biosensors, biomarkers, and biological survey are briefly reviewed.

PMID- 15462140
TI  - Design of vector quantizer for image compression using self-organizing feature
      map and surface fitting.
AB  - We propose a new scheme of designing a vector quantizer for image compression.
      First, a set of codevectors is generated using the self-organizing feature map
      algorithm. Then, the set of blocks associated with each code vector is modeled by
      a cubic surface for better perceptual fidelity of the reconstructed images. Mean
      removed vectors from a set of training images is used for the construction of a
      generic codebook. Further, Huffman coding of the indices generated by the encoder
      and the difference-coded mean values of the blocks are used to achieve better
      compression ratio. We proposed two indices for quantitative assessment of the
      psychovisual quality (blocking effect) of the reconstructed image. Our
      experiments on several training and test images demonstrate that the proposed
      scheme can produce reconstructed images of good quality while achieving
      compression at low bit rates. Index Terms-Cubic surface fitting, generic
      codebook, image compression, self-organizing feature map, vector quantization.

PMID- 15462141
TI  - Automatic foveation for video compression using a neurobiological model of visual
      attention.
AB  - We evaluate the applicability of a biologically-motivated algorithm to select
      visually-salient regions of interest in video streams for multiply-foveated video
      compression. Regions are selected based on a nonlinear integration of low-level
      visual cues, mimicking processing in primate occipital, and posterior parietal
      cortex. A dynamic foveation filter then blurs every frame, increasingly with
      distance from salient locations. Sixty-three variants of the algorithm (varying
      number and shape of virtual foveas, maximum blur, and saliency competition) are
      evaluated against an outdoor video scene, using MPEG-1 and constant-quality MPEG
      4 (DivX) encoding. Additional compression radios of 1.1 to 8.5 are achieved by
      foveation. Two variants of the algorithm are validated against eye fixations
      recorded from four to six human observers on a heterogeneous collection of 50
      video clips (over 45 000 frames in total). Significantly higher overlap than
      expected by chance is found between human and algorithmic foveations. With both
      variants, foveated clips are, on average, approximately half the size of
      unfoveated clips, for both MPEG-1 and MPEG-4. These results suggest a general
      purpose usefulness of the algorithm in improving compression ratios of
      unconstrained video.

PMID- 15462142
TI  - Indexing of multidimensional lookup tables in embedded systems.
AB  - The proliferation of color devices and the desire to have them accurately
      communicate color information has led to a need for embedded systems that perform
      color conversions. A common method for performing color space conversions is to
      characterize the device with a multidimensional lookup table (MLUT). To reduce
      cost, many of the embedded systems have limited computational abilities. This
      leads to a need for the design of efficient methods for performing MLUT indexing
      and interpolation. This paper examines and compares two methods of MLUT indexing
      within embedded systems. The comparison is made in terms of colorimetric accuracy
      and computational cost.

PMID- 15462143
TI  - Fast and robust multiframe super resolution.
AB  - Super-resolution reconstruction produces one or a set of high-resolution images
      from a set of low-resolution images. In the last two decades, a variety of super
      resolution methods have been proposed. These methods are usually very sensitive
      to their assumed model of data and noise, which limits their utility. This paper
      reviews some of these methods and addresses their short-comings. We propose an
      alternate approach using L1 norm minimization and robust regularization based on
      a bilateral prior to deal with different data and noise models. This
      computationally inexpensive method is robust to errors in motion and blur
      estimation and results in images with sharp edges. Simulation results confirm the
      effectiveness of our method and demonstrate its superiority to other super
      resolution methods.

PMID- 15462144
TI  - Noise removal using smoothed normals and surface fitting.
AB  - In this work, we use partial differential equation techniques to remove noise
      from digital images. The removal is done in two steps. We first use a total
      variation filter to smooth the normal vectors of the level curves of a noise
      image. After this, we try to find a surface to fit the smoothed normal vectors.
      For each of these two stages, the problem is reduced to a nonlinear partial
      differential equation. Finite difference schemes are used to solve these
      equations. A broad range of numerical examples are given in the paper.

PMID- 15462145
TI  - Markov random field models for directional field and singularity extraction in
      fingerprint images.
AB  - A Bayesian formulation is proposed for reliable and robust extraction of the
      directional field in fingerprint images using a class of spatially smooth priors.
      The spatial smoothness allows for robust directional field estimation in the
      presence of moderate noise levels. Parametric template models are suggested as
      candidate singularity models for singularity detection. The parametric models
      enable joint extraction of the directional field and the singularities in
      fingerprint impressions by dynamic updating of feature information. This allows
      for the detection of singularities that may have previously been missed, as well
      as better aligning the directional field around detected singularities. A
      criteria is presented for selecting an optimal block size to reduce the number of
      spurious singularity detections. The best rates of spurious detection and missed
      singularities given by the algorithm are 4.9% and 7.1%, respectively, based on
      the NIST 4 database.

PMID- 15462146
TI  - A Bayesian filtering technique for SAR interferometric phase fields.
AB  - SAR interferograms are affected by a strong noise component which often prevents
      correct phase unwrapping and always impairs the phase reconstruction accuracy. To
      obtain satisfactory performance, most filtering techniques exploit prior
      information by means of ad hoc, empirical strategies. In this paper, we recast
      phase filtering as a Bayesian estimation problem in which the image prior is
      modeled as a suitable Markov random field, and the filtered phase field is the
      configuration with maximum a posteriori probability. Assuming the image to be
      residue free and generally smooth, a two-component MRF model is adopted, where
      the first component penalizes residues, while the second one penalizes
      discontinuities. Constrained aimulated annealing is then used to find the optimal
      solution. The experimental analysis shows that, by gradually adjusting the MRF
      parameters, the algorithm filters out most of the high-frequency noise and, in
      the limit, eliminates all residues, allowing for a trivial phase unwrapping.
      Given a limited processing time, the algorithm is still able to eliminate most
      residues, paving the way for the successful use of any subsequent phase
      unwrapping technique.

PMID- 15462147
TI  - A downstream algorithm based on extended gradient vector flow field for object
      segmentation.
AB  - For object segmentation, traditional snake algorithms often require human
      interaction; region growing methods are considerably dependent on the selected
      homogeneity criterion and initial seeds; watershed algorithms, however, have the
      drawback of over segmentation. A new downstream algorithm based on a proposed
      extended gradient vector flow (E-GVF) field model is presented in this paper for
      multiobject segmentation. The proposed flow field, on one hand, diffuses and
      propagates gradients near object boundaries to provide an effective guiding force
      and, on the other hand, presents a higher resolution of direction than
      traditional GVF field. The downstream process starts with a set of seeds scored
      and selected by considering local gradient direction information around each
      pixel. This step is automatic and requires no human interaction, making our
      algorithm more suitable for practical applications. Experiments show that our
      algorithm is noise resistant and has the advantage of segmenting objects that are
      separated from the background, while ignoring the internal structures of them. We
      have tested the proposed algorithm with several realistic images (e.g., medical
      and complex background images) and gained good results.

PMID- 15462148
TI  - Design and statistical analysis of a hash-aided image watermarking system.
AB  - This paper develops a joint hashing/watermarking scheme in which a short hash of
      the host signal is available to a detector. Potential applications include
      content tracking on public networks and forensic identification. The host data
      into which the watermark is embedded are selected from a secret subset of the
      full-frame discrete cosine transform of an image, and the watermark is inserted
      through multiplicative embedding. The hash is a binary version of selected
      original image coefficients. We propose a maximum likelihood watermark detector
      based on a statistical image model. The availability of a hash as side
      information to the detector modifies the posterior distribution of the marked
      coefficients. We derive Chernoff bounds on the receiver operating characteristic
      performance of the detector. We show that host-signal interference can be
      rejected if the hash function is suitably designed. The relative difficulty of an
      eavesdropper's detection problem is also determined; the eavesdropper does not
      know the secret key used. Monte Carlo simulations are performed using
      photographic test images. Finally, various attacks on the watermarked image are
      introduced to study the robustness of the derived detectors. The joint
      hashing/watermarking scheme outperforms the traditional "hashless" watermarking
      technique.

PMID- 15462149
TI  - Health effects of diazinon on a family.
AB  - There is increasing evidence of permanent sequalae from acute organophosphate
      poisoning. We report on accidental diazinon overexposure with acute
      organophosphate poisoning through cutaneous absorption and inhalation followed by
      persistent neurological effects. In addition, we observed skeletal and endocrine
      effects likely attributable to the diazinon poisoning. A family of seven was
      exposed to diazinon in June 1999 over a two-day period. The pesticide company
      mistakenly used diazinon to heavily spray the inside of the home instead of
      permethrin. The applicator applied the pesticide over the entire surface of the
      floor, carpeting, furniture, and clothing in closets to eradicate an infestation
      of fleas. Acute symptoms in the family members included headaches, nausea, skin
      irritation, runny nose, and vomiting. The family was first evaluated at 3 months
      and then 3 years after the acute poisoning. There were persisting neurological
      symptoms of memory loss, decreased concentration, irritability, and personality
      changes of varying degrees in all family members. Objective neurological findings
      of impaired balance, reaction time, color vision, slotted pegboards and trials
      making were present in the three older children who could be tested.
      Neuropsychological evaluation revealed evidence of organic brain dysfunction in
      all seven family members. Bone growth difficulties are present in four of five
      children. One child has delayed menarche.

PMID- 15462150
TI  - Retrospective review of Tizanidine (Zanaflex) overdose.
AB  - BACKGROUND: Tizanidine is a centrally acting muscle relaxant with a novel
      mechanism of action and structurally related to clonidine. There are no large
      case series of tizanidine exposure. METHODS: Retrospective review of all
      ingestions involving tizanidine reported to a poison control center from January
      2000 through February 2003. Exclusion criteria were polydrug ingestion, no follow
      up or lost to follow-up. RESULTS: There were 121 cases of which 45 patients met
      entrance criteria. Mean age was 32 years (range 1 to 80). Thirty-seven patients
      were evaluated in a health care facility of which 27 were admitted for medical
      care. Clinical effects included lethargy (n = 38), bradycardia (n = 14),
      hypotension (n = 8), agitation (n = 7), confusion (n = 5), vomiting (n = 3), and
      coma (n = 2). Mean dose ingested by history was 72 mg (S.D. + 86). The lowest
      dose associated with hypotension was 28mg, which occurred in a 63-year-old female
      with a BP of 88/52 and a HR of 54. The lowest dose associated with coma was
      between 60 mg and 120 mg, which occurred in a 30-year-old female with a HR of 30
      and BP of 81/48. There were 6 patients < 6 yrs. The lowest dose with bradycardia
      and drowsiness in a small child was 16 mg in a 2 YO (weight unknown). All other
      cases in children < 6 yrs involved ingestion of a single tablet (2 or 4 mg) with
      only mild drowsiness reported. Therapy in this series was primarily supportive
      and included pressors in 3 cases and intubation in 3 cases. Naloxone was
      administered to 7 patients. There was no response to naloxone in 5 patients, poor
      documentation of response in one, and arousal in one patient. All patients
      recovered without residual complications. CONCLUSION: Clinical manifestations of
      tizanidine overdose include alterations of mental status, bradycardia, and
      hypotension. In this series, outcome was good with supportive therapy.

PMID- 15462151
TI  - Analysis of moonshine for contaminants.
AB  - OBJECTIVES: In the past, some moonshine products contained potentially toxic
      contaminants. Although moonshine production continues in the United States, no
      studies have analyzed the content of moonshine since the early 1960s. We
      hypothesize that moonshine continues to contain potentially toxic concentrations
      of contaminants. METHODS: Forty-eight samples of illicitly distilled moonshine
      were obtained from law enforcement agencies. An independent laboratory, blinded
      to both the moonshine source and a control sample of ethanol, conducted the
      analysis. Lead content was determined using atomic absorption spectrophotometry
      with a graphite tube atomizer. Alcohol content, including ethanol, acetone,
      isopropanol, methanol, and ethylene glycol, was determined using gas liquid
      chromatography with flame ionization detection. RESULTS: Ethanol content ranged
      from 10.5% to 66.0% with a mean value of 41.2%. Lead was found in measurable
      quantities in 43 of 48 samples with values ranging from 5 to 599 parts per
      billion (ppb) with a mean value of 80.7 ppb. A total of 29 of 48 (60%) of samples
      contained lead concentrations above or equal to the EPA water guideline of 15
      ppb. Methanol was found in only one sample at a concentration of 0.11%. No
      samples contained detectable concentrations of acetone, isopropanol, or ethylene
      glycol. CONCLUSIONS: Many moonshine samples contain detectable concentrations of
      lead. Extrapolations based on the described moonshine lead content suggest that
      chronic consumers of moonshine may develop elevated lead concentrations.
      Physicians should consider lead toxicity in the differential diagnosis when
      evaluating patients consuming moonshine.

PMID- 15462152
TI  - Compliance with poisons center referral advice and implications for
      toxicovigilance.
AB  - BACKGROUND: When Poisons Information, or Poisons Control Centers (PCC) give
      directive advice in response to general public calls it is usually assumed that
      the advice will be followed, but it is difficult to measure the actual compliance
      of callers to a PCC. Epidemiological data regarding the incidence of poisoning
      incidents (Toxicovigilance) often utilizes reports of calls to a PCC. METHODS:
      Retrospective review of advice given to all callers to the New Zealand National
      Poisons Centre (NZNPC) from a defined area for the calendar year 2001. Callers to
      the NZNPC telephone hotlines who were advised to attend or not to attend the
      hospital Emergency Department (ED) were subsequently matched with actual ED
      visits. RESULTS: The compliance rate for those advised to attend the ED was
      76.1%, whereas those advised not to attend had a compliance rate of 98.7%. The
      overall compliance rate was 94.1%. Of the patients presenting to the ED with a
      potential poisoning, only 10.2% were referred by the PCC. The callers referred by
      PCC and direct ED visitors appeared to differ in some respects. CONCLUSIONS:
      Compliance with PCC telephone advice is similar to the compliance rates in many
      other health interventions. Comparisons between populations calling a PCC and
      those self-presenting to an ED show that PCC data may not reflect the true burden
      of poisoning to health care systems.

PMID- 15462153
TI  - Doctors and nurses estimation of the weight of patients: A preventable source of
      systematic error.
AB  - BACKGROUND: Although accurate determination of body weight is important in the
      management of the poisoned patient, many patients have their weight estimated
      rather than formally measured. OBJECTIVE: To determine how good medical staff are
      at estimating patients*** body weights. METHODS: Medical staff were asked to
      estimate the weight of six patients on a poisons ward. Estimated and actual
      patient weights were statistically compared. RESULTS: Medical staff produced a
      large range of estimated weights for all patients. Patient weight was incorrectly
      estimated by greater than 10% in 61% of individual estimations. There was poor
      statistical correlation between actual and estimated weight. CONCLUSIONS: All
      patients administered medication based on body weight and those treated following
      an overdose of any substance should have formal body weight determined as part of
      their standard management.

PMID- 15462154
TI  - The effects of fresh frozen plasma on cholinesterase levels and outcomes in
      patients with organophosphate poisoning.
AB  - OBJECTIVE: The aim of this study is to determine the effects of fresh frozen
      plasma, as a source of cholinesterase, on butyrylcholinesterase (BuChE; plasma or
      pseudo cholinesterase) levels and outcomes in patients with organophosphate
      poisoning. MATERIALS AND METHODS: This prospective study was performed at the
      Department of Intensive Care of Erciyes University Medical School. Over 2 yrs,
      patients admitted to the ICU for OP poisoning were entered into the study. OP
      poisoning was diagnosed on the basis of history and BuChE levels. All patients
      received atropine. Fresh frozen plasma was given to 12 patients. The study was
      approved by the Ethical Committee, and verbal informed consent was obtained.
      RESULTS: Thirty-three patients were included in the study. BuChE levels measured
      at admission and the pralidoxime and atropine doses administered were not
      different between groups (p>0.05). Although intermediate syndrome developed in
      28.6% of patients receiving pralidoxime, there were no intermediate syndrome
      cases in patients receiving plasma prior to developing intermediate syndrome. The
      mortality rates were 14.3% in the pralidoxime group and 0% in the
      plasma+atropine+pralidoxime group. Two patients received plasma after developing
      the intermediate syndrome, and one patient who received only atropine died. BuChE
      levels of fresh frozen plasma were 4069.5 +/- 565.1 IU/L. Every two bags of
      plasma provided an increase in BuChE levels of approximately 461.7 +/- 142.1
      IU/L. CONCLUSION: Fresh frozen plasma therapy increases BuChE levels in patients
      with organophosphate poisonings. The administration of plasma may also prevent
      the development of intermediate syndrome and related mortality. Plasma (fresh
      frozen or freshly prepared) therapy may be used as an alternative or adjunctive
      treatment method in patients with organophosphate pesticide poisoning, especially
      in cases not given pralidoxime. Further randomized controlled and animal studies
      are required to infer a definitive result.

PMID- 15462155
TI  - Regional variations in the use and awareness of the California Poison Control
      System.
AB  - PURPOSE: To investigate regional variations in public awareness and utilization
      of the services of Poison Control Centers (PCC) before and after an intervention.
      METHODS: This study examines call rates of different California regions based on
      the final five regional PCCs prior to the consolidation of these services under a
      single statewide California Poison Control System (CPCS) and interventions to
      increase utilization. Awareness surveys were performed before and after a media
      campaign that was directed primarily to the Los Angeles basin and to a lesser
      extent other high Hispanic concentration areas. Focus groups were also utilized
      to better define specific areas of poison knowledge and awareness of CPCS
      services. FINDINGS: Large differences in regional California call rates were
      seen, with the Los Angeles basin showing the lowest utilization of CPCS services
      compared with the rest of California. Significant seasonal variation in
      utilization was also found, with the highest average call rates observed in
      August and the lowest in February. Focus groups demonstrated that urban awareness
      of PCC was lower than suburban awareness, particularly in monolingual Hispanic
      households. An improvement was seen after the institution of a media education
      campaign that included use of Spanish language material and radio spots. Similar
      increases in call rates were also seen in Fresno county category, with a higher
      percentage of Hispanic population that was not as aggressively targeted by the
      awareness campaign. CONCLUSIONS: Significant regional variations in CPCS call
      rates were found and an increased awareness and utilization was seen in the Los
      Angeles basin after a directed media campaign compared with most areas of
      California. Further efforts to increase CPCS utilization in the Los Angeles
      region, primarily among urban monolingual Hispanics, are needed.

PMID- 15462156
TI  - Rattlesnake bites in Europe--experiences from southeastern France and northern
      Germany.
AB  - INTRODUCTION: Rattlesnakes are indigenous to the New World and hence their
      envenomations are a significant percentage of all poisonings in North and South
      America. Some years ago rattlesnake bites were virtually unknown in Europe. But
      the biodiversity of European household fauna has changed: cats and dogs are
      increasingly replaced by stingrays, tarantulas, fire fish, and rattlesnakes. This
      phenomenon is the background of a French-German cooperation to evaluate the
      relevance of rattlesnake bites for European doctors. MATERIAL AND METHODS: In a
      retrospective study all consultations of the GIZ-Nord poison centre in Gottingen
      and the Centre Antipoison in Marseille concerning bites of poisonous snakes in a
      20-yr time period were analyzed. RESULTS: Altogether 671 cases of poisonous snake
      bites were registered. Rattlesnake bites came up to 21 (3.1% of all consultations
      due to poisonous snake bites). Over the years the number increased constantly.
      All patients were adult men with a mean age of 37.2 (20-64) years. There were no
      females and no pediatric patients involved. According to the Poisoning Severity
      Score there were 8 minor, 5 moderate, and 8 severe envenomations; no fatalities.
      The leading clinical symptoms consisted of rhabdomyolysis, neurological, and
      coagulational disorders. In 5 cases antivenom therapy was applied, and in 4
      patients surgical therapy was performed. CONCLUSION: Rattlesnake bites are rare
      in Europe, but the incidence is rising. The patients' profile is different from
      large American case series. European doctors should be aware of the increase in
      these infrequent envenomations.

PMID- 15462157
TI  - Characteristics of patients with no underlying toxicologic syndrome evaluated in
      a toxicology clinic.
AB  - BACKGROUND: A significant number of patients seek medical evaluation for chronic
      subjective symptoms they presume to be associated with a single toxic trigger.
      This report describes our clinic experience with these patients. CASE SERIES:
      Twenty patients (of a total of 261 patients) with a mean age of 41 years (median
      age 42 years; range: 4 to 65 years) were evaluated over an 8 month period. All
      describe a single past toxic exposure triggering their nonspecific (usually
      vaguely neurologic) symptoms. Zero of 20 (0%) describe other chemical
      sensitivities; 2/20 (10%) report ongoing exposure, 18/20 (90%) had a limited
      exposure dating 1 month to 6 yrs prior to toxicology clinic evaluation; 9/20
      (45%) are currently employed; 6/20 (30%) sought alternative medical therapy prior
      to toxicologist evaluation; 6/20/(30%) have attempted litigation. CONCLUSION:
      Despite repeatedly normal toxicologic and medical evaluations, all data refuting
      an underlying toxic cause are not accepted by this series of patients, and their
      search for a diagnostic linkage persists. Specific toxin identification or
      treatment for these patients is unlikely to occur.

PMID- 15462158
TI  - Forearm compartment syndrome after intravenous mannitol extravasation in a
      carbosulfan poisoning patient.
AB  - We report a case of forearm compartment syndrome caused by extravasation of
      mannitol in an intoxicated patient. The pathophysiology and management of a
      forearm compartment syndrome from extravasation of mannitol are discussed in this
      case.

PMID- 15462159
TI  - Iron bezoar retained in colon despite 3 days of whole bowel irrigation.
AB  - Concretion formation is a documented complication of large iron ingestions. The
      generally accepted treatment is supportive care, whole bowel irrigation, and
      intravenous deferoxamine for systemic toxicity. Laparotomy and gastrotomy have
      also been used in patients with a high iron burden and bezoar formation. Though
      experiments suggest that iron is poorly absorbed in the colon, there are no case
      reports of iron overdose without systemic toxicity, despite a retained colonic
      bezoar. We report the case of a 16-month-old who presented to an Emergency
      Department 19 h after an iron ingestion. Initial laboratory studies revealed an
      anion gap of 14 mEq/L, and a 20 h serum iron concentration of 429 mcg/dL. An
      abdominal radiograph revealed multiple pills throughout the stomach and small
      bowel; whole bowel irrigation was initiated. Deferoxamine was administered at 10
      mg/kg/h and then stopped when the serum iron level reached 27 mcg/dL, 36 h later.
      At this time, the abdominal radiograph showed an iron bezoar remaining in the
      ascending colon despite a clear rectal effluent from whole bowel irrigation.
      Despite whole bowel irrigation over the next 36 h, the iron bezoar was not
      removed and actually migrated proximally in the colon. Treatment was stopped on
      the third day and a normal diet was instituted with prompt passage of the bezoar.

PMID- 15462160
TI  - Acute poisoning with emamectin benzoate.
AB  - BACKGROUND: Emamectin benzoate is the 4'-deoxy-4'-epi-methyl-amino benzoate salt
      of avermectin B1 (abamectin), which is similar structurally to natural
      fermentation products of Streptomyces avermitilis. Emamectin benzoate is being
      developed as a newer broad-spectrum insecticide for vegetables and has a very low
      application rate. The mechanism of action involves stimulation of high-affinity
      GABA receptors and a consequent increase in membrane chloride ion permeability.
      Animal studies indicate a wide margin of safety because mammalian species are
      much less sensitive due to lower GABA receptor affinities and relative
      impermeability of the blood-brain barrier. Notably, the literature has not
      reported human exposure resulting in toxicity. CASE REPORT: This paper describes
      a case of acute poisoning with Proclaim insecticide (Syngenta, Taiwan),
      consisting of 2.15% w/w emamectin benzoate in 2, 6-bis (1, 1-dimethylethyl)-4
      methyl-phenol and 1-hexanol. The clinical manifestation was transient
      gastrointestinal upset with endoscopy-proven gastric erosion and superficial
      gastritis, mild central nervous system depression, and aspiration pneumonia. No
      specific antidote exists for emamectin benzoate intoxication; this patient was
      treated successfully with gastric lavage, administration of activated charcoal,
      and empiric antibiotics. Drugs that enhance GABA activity such as barbiturates
      and benzodiazepines were avoided.

PMID- 15462161
TI  - The oral toxicity of resorcinol during pregnancy: a case report.
AB  - Resorcinol (1,3 benzenediol; m-dihydroxybenzene: resorcin) is a pharmaceutical
      agent used topically in dermatological treatments such as acne and related skin
      conditions. It could also be used in combination with the other acne treatment
      agents such as sulphur. It could be very hazardous if taken orally and there are
      limited reports on its toxic effects in human. The present work aimed to report a
      resorcinol poisoning case in which resorcinol was taken accidentally by a woman
      at 30 weeks of pregnancy. The major clinical findings were unconsciousness,
      drowsiness, and respiratory failure that required mechanical ventilation along
      with tonic-clonic seizures and hypothermia. In addition, the laboratory findings
      were leucocytosis, high bilirubin levels, severe metabolic acidosis, and green
      colored urine. The fetus was considered dead 24 h after delivery; however,
      mother's prognosis was well with supportive management. It could be concluded
      that the basic approach to the patient with resorcinol poisoning should include
      the initial stabilization of immediate life-threatening problems and elimination
      of the toxin. This is the first report on resorcinol poisoning in pregnant women,
      indicating its major clinical and laboratory findings.

PMID- 15462162
TI  - Severe bone marrow depression induced by an anticancer herb Cantharanthus roseus.
AB  - We report a 67-yr-old woman with hepatitis C-related liver cirrhosis and hepatoma
      who had developed severe bone marrow suppression after taking Cantharanthus
      roseus as an alternative anticancer treatment. The patient developed severe
      pancytopenia with initial presentations of vomiting, diarrhea, oral ulcer, and
      fever about 1 week after taking 5-days' course of Cantharanthus roseus. Bone
      marrow biopsy showed autolysis, which indicated massive necrosis of the
      hematopoietic cells. There was no malignant cell infiltration. The patient also
      had severe gastrointestinal disturbances, bacteremia, urinary tract infection,
      and impaired renal and liver function. Supportive care with broad-spectrum
      antibiotics, granulocyte colony-stimulating factor, repeated blood transfusions,
      and albumin supplement was given. She recovered and was discharged after 48 days
      hospitalization. Coadministration of Cantharanthus roseus and cisapride was
      noted, and these two drugs are both substrates of cytochrome P450 3A4 enzymes
      (CYP 3A4). Because the vinca alkaloids are extensively metabolized by the liver
      cytochrome P450 enzymes, poor hepatic function and drug-herb interaction might
      predispose the patient to develop the bone marrow toxicity. This case report
      demonstrated possible effect of oral dose of vinca alkaloids and also hinted that
      all the substrates and inhibitors of CYP 3A4 have propensity to interfere with
      metabolism of vinca alkaloids.

PMID- 15462163
TI  - Methanol toxicity in a newborn.
AB  - BACKGROUND: Methanol poisoning during human pregnancy rarely has been described.
      We report the first human newborn with a documented methanol concentration
      resulting from maternal exposure. CASE REPORT: A 28-year-old pregnant woman EGA
      30 weeks with HIV infection and asthma presented to the emergency department in
      respiratory distress. She was acidotic (pH 7.17) with an anion gap of 26, and
      fetal bradycardia was noted. Her son was delivered by emergent C-section
      (birthweight 950 g, Apgars 1 and 3) and required aggressive resuscitation. During
      his hospital course, acidosis (initial pH 6.9) persisted despite fluid, blood,
      and bicarbonate administration. His mother also had persistent metabolic acidosis
      despite fluids, bicarbonate, and dopamine. Results of other laboratory tests on
      the mother included undetectable ethanol and salicylates and an osmolar gap of
      41. An ethanol drip was initiated for the mother 36 h after admission when a
      methanol level of 54 mg/dL was reported. When consulted on hospital day 3, our
      regional poison center recommended hemodialysis for the mother and administering
      fomepizole and testing the methanol level of the newborn (61.6 mg/dL). Because
      the infant developed a grade 4 intraventricular bleed, no further therapy was
      offered, and he died on day 4. His mother died on day 10. CONCLUSION: Fatal
      neonatal methanol toxicity can result from transplacental exposure.

PMID- 15462164
TI  - Comprehensive toxicology drug screening data in a pediatric population.

PMID- 15462165
TI  - [Recurrences of pleomorphic adenomas of the parotid: development of concepts].
AB  - OBJECTIVES: The aim of this study was to examine the surgical and pathological
      factors that led to recurrent parotid pleomorphic adenomas. The study also tried
      to determine best practice for the treatment of recurrence. In addition the study
      looked at the correlation between fine needle cytology and definitive histology.
      MATERIAL AND METHOD: Histological study was undertaken on 100 pleomorphic
      adenomas surgically removed from patients in our institution between 1992 and
      2002. Study of diagnostic value of fine needle cytology aspiration and MRI for
      pleomorphic adenoma diagnosis was performed in 181 patients operated on for
      parotid tumors. RESULTS: Hypocellular pleomorphic adenomas often have a thin
      capsule and constitute the most frequently encountered histological type in
      recurrence. Pseudopodias are considered as an additional factor in recurrence. In
      our series, cytological study had an excellent diagnostic value with a
      sensitivity of 92% and a PPV of 96%. MRI study had a sensitivity of 83% and a PPV
      of 89%. CONCLUSIONS: According to these findings, enucleation surgery on a
      pleomorphic adenoma should not be performed anymore. Parotidectomy techniques
      (total or lateral) constitute the surgical treatment of choice. Fine needle
      aspirate cystology in a useful diagnostic procedure. Management of recurrences is
      based on surgery with total parotidectomy and facial nerve preservation. Role of
      radiotherapy is still indeterminate.

PMID- 15462166
TI  - [Induction chemotherapy and laryngeal preservation in pharyngolaryngeal
      carcinomas. Study of a 124 serie's patients and patient's follow up with
      laryngeal preservation].
AB  - OBJECTIVE: To try and determine the value of chemotherapy and its subsequent
      effect on laryngeal preservation in patients presenting with laryngeal and
      pharyngeal carcinomas. One group was initially treated with surgery and
      radiotherapy. The second group was treated with chemotherapy and subsequent
      salvage surgery and/or radiotherapy. Their survival rates and laryngeal
      preservation rates were compared. PATIENTS AND METHODS: From 251 patients the
      authors have retrospectively studied 124 patients with induction chemotherapy.
      The survival rate has been compared with a control group of 127 patients who was
      treated by initial surgery and radiotherapy. RESULTS: The survival rate at 5
      years for the patients initially treated by surgery and radiotherapy was 64.1%.
      The survival for patients with a total clinical response following chemotherapy
      was 49.8% at 5 years. Survival with no total clinical response following
      chemotherapy treated by secondary radiotherapy was 25.7% at 3 years. The initial
      rate of laryngeal preservation is 32.2% but this rate fell to 22% after local
      recurrencies. CONCLUSION: The group with total clinical response after induction
      chemotherapy with laryngeal preservation have a non significantly difference in
      their survival compared with the group initially treated by surgery and
      radiotherapy. In contrary patients with non complete clinical response have a
      survival of 25.7% at 3 years. The rate of local recurrency of patients with
      laryngeal preservation is 32.5% and gives a finally rate of laryngeal
      preservation of 21%. These recurrencies decrease the survival rate.

PMID- 15462167
TI  - [Vocal rehabilitation with tracheoesophageal prosthesis. Study of peri-prosthetic
      leakages].
AB  - OBJECTIVES: Peri-prosthetic leakages are a frequent complication of
      tracheoesophageal prosthesis used in the vocal rehabilitation of laryngectomized
      patients. The authors examine the effect of pre or post operative radiotherapy
      upon the incidence of this complication. MATERIALS AND METHOD: In a retrospective
      study of 67 patients rehabilited with a phonatory prosthesis between 1993 and
      2002, pre or post-operative radiotherapy was carried out in 61 patients. RESULTS:
      A peri-prosthetic leakage occured in 38.8% of the cases. The pre or post
      operative radiotherapy was not a statistically significant cause of leakage, as
      the age of the patient and the surgical procedure. CONCLUSION: Although not
      supported by the statistical study because of a lack of cases, the radiotherapy
      remains for the authors a factor determining in the mechanism of the peri
      prosthetic leakages and bad forecast for their treatment. Realized before the
      surgery, it contra-indicates the phonatory prosthesis at the time of the tumor
      resection. In case of post-operative radiotherapy, the risks must be clearly
      explained to the patient.

PMID- 15462168
TI  - [Pharyngolaryngectomy for advanced and recurrent cancer: prognostic factors and
      complications].
AB  - INTRODUCTION: The aim of this study was to evaluate the results of the initial
      surgical treatment and salvage treatment for advanced laryngopharyngeal cancer.
      METHODS: From 1984 to 1997, primary surgical treatment was undertaken in 60
      patients. 75 patients underwent surgical salvage following radiotherapy. RESULTS:
      55/135 patients (40.7%) experienced local regional relapse. The overall survival
      at 5 years was 43.9% in the first group of patients treated initially with
      surgery. In the group of patients treated with salvage surgery, the overall
      survival at 5 years was 40.2%. A multivariate analysis showed that involved lymph
      nodes (p = 0.0004), a nutritional score inferior to 5 (p = 0.03), positive
      resection margins (hazard ratio 2.05; 95% c.i. 1.03 to 4.04 ; p = 0.03), a local
      regional relapse (p = 0.04) and appearance of metastasis (p = 0.03) were
      independent risk factors for overall survival. Survival is dependent from each
      factor, and each factor is independent from each other Stenosis was rare: 5.1% in
      the present series. A pharyngocutaneous fistula developed in 49.6% of patients.
      After a multivariate analysis, the site of the tumor (odds 2.26; 95% c.i. 1.05 to
      4.85; p = 0.03) had an influence for apparition of a fistula. CONCLUSION: Initial
      surgical surgery and salvage surgery of respectively 43.9% and 40.2% overall
      survival compares favorably with the literature. Despite progress made with
      reconstruction, morbidity is still elevated in a selected group defined after
      analysis of pronostic factors.

PMID- 15462169
TI  - [The verrucous laryngeal carcinoma. A rare tumor with a difficult diagnosis].
AB  - OBJECTIVES: The authors report a single case of laryngeal verrucous carcinoma and
      review the literature. MATERIALS AND METHOD: The delay of the diagnosis, the
      difficulties in its establishment and the therapeutic methods are discussed in a
      review of the literature. RESULTS: Histopathological diagnosis remains difficult.
      This may explain a great number of mistakes and the subsequent delay of in
      treatment. The role of radiotherapy is discussed. CONCLUSION: The diagnosis and
      management of the laryngeal verrucous carcinoma is difficult.

PMID- 15462170
TI  - [Laryngeal papillomatosis in adults: report on 4 cases].
AB  - Laryngeal papillomatosis is well-known as one part of benign lesions of the
      larynx in children under 15 years. Cases of papillomatosis are extremely rare in
      adults. OBJECTIVES: To report our experience about 4 cases. MATERIAL AND METHOD:
      It concerns 3 females and 1 male, who are in good health and without any disease
      in relation of upper respiratory tract or viruses. For all patients there is no
      familiar viral disease (especially cutaneous or genital). The age of patients is
      between 28 and 72 years. All clinical signs at the diagnosis aren't specific and
      are observed in other laryngeal diseases. Direct micro-laryngoscopy is mandatory
      in order to establish the right diagnosis and to perform the first stage of local
      treatment. Micro-instruments are used to remove these benign nipple-like without
      CO2 laser or local medicines or injections. RESULTS: Our study mentions a
      frequent association of gastro-oesophageal reflux (3 cases). The average follow
      up is 5 years and half and in this period, there is no malignant evolution.
      CONCLUSION: The authors also review the literature and in particular the
      potential cause of laryngeal papillomatosis and new ideas on treatment of this
      unusual condition.

PMID- 15462171
TI  - [The supracricoid laryngectomy with cricohyoidopexy. Carcinological and
      functional results. 23 cases report of the Centre A. Lacassagne (Nice)].
AB  - OBJECTIVE: This study is to estimate the survival results, the morbidity and the
      functional consequences of the supracricoid laryngectomy with cricohyoidopexy (SL
      CHP). PATIENTS AND METHODS: Between 1990 and 2001, 23 patients had a SL-CHP in
      Centre Antoine Lacassagne of Nice. The average age was of 59 years. Patients were
      classified as follow: 1 T1, 11 T2, 10 T3 and 1 T4 (invasion of the thyroid
      cartilage without involving of anterior soft tissues). 17 patients were NO
      (73.9%). A bilateral radical neck dissection was performed in 10 cases, a radical
      neck dissection was associated to a functional neck dissection (1 case) and a
      homolateral functional neck dissection (10 cases). RESULTS: The limits were
      insufficient for a patient. Six patients were N+ (28.5%) of which 4 N+R+. The
      average delay was 21 days and 32.7 days to remove respectively the tracheotomy
      and the nasogastric tube. A functional total laryngectomy was done in two cases.
      We noted two cases of local recurrence. Survivals according to the method of
      Kaplan-Meier are 81% in 3 years and 75% in 5 years. CONCLUSION: The SL-CHP
      represents an alternative to the total laryngectomy for the supraglottic and
      transglottic carcinomas.

PMID- 15462172
TI  - [Newborn and infant nasal dyspnea].
AB  - OBJECTIVE: The aim of this study is to report our experience of causes of newborn
      and infant nasal obstruction. METHODS: Four cases (3 newborns, 1 infant) of nasal
      dyspnea are reported. For each of them, background circumstances, diagnostic and
      therapeutic methods and outcomes are reported. Based on a review of the
      literature, the main causes of nasal obstruction and their treatments are
      discussed. RESULTS: In all cases, the diagnosis was made by the rhinoscopy with
      an endoscope and CT-Scan. Choanal atresia, infectious rhinitis, bilateral lacrymo
      nasal cyst and nasopharyngeal hamartoma were diagnosed, and associated with
      respiratory distresses or difficulties in feeding. The treatment consisted of
      simple removal of the nasopharyngeal hamartoma, marsupialization for the lacrymo
      nasal cysts, antibiotherapy and stenting for a few weeks for the infectious
      rhinitis and permeabilization by puncture and stenting for the choanal atresia.
      The outcome was successful in all cases. CONCLUSION: Newborn and infant nasal
      dyspnea is a serious disease. This study underlines the importance of efficient
      and rapid management. Knowledge of the possible causes grouped in three
      categories--malformative, tumoral and infectious--is mandatory to make the
      appropriate choice.

PMID- 15462173
TI  - [Viral assumption and inverted papilloma: role of human herpes viridae n 8].
AB  - INTRODUCTION: The aetiology of inverted papillomas is still not known. Current
      thinking favours a viral agent in particular OBJECTIVE: To widen viral research
      to "Human Herpes Viridae n 8" (HHV 8). MATERIAL AND METHOD: 14 patients were
      included in a prospective study over a 38 months period. The average age was 49.6
      years. The technique used is the PCR. RESULTS: No samples revealed the presence
      of HHV n8. CONCLUSION: The virus "human herpes viridae" was found in no samples,
      but as long as the etiopathogeny of the inverted papilloma is unknown. Further
      viral research is needed.

PMID- 15462174
TI  - Mucormycosis--early diagnosis and treatment.
AB  - OBJECTIVE: The aim of this retrospective study was to analyse the data of
      patients with rhino-orbital-cerebral mucormycosis for predisposing factors,
      diagnosis, treatment and survival rate. The role of frozen section in early
      diagnosis and use of nasal endoscopy in diagnosis, treatment and follow-up of
      patients has also been examined. DESIGN: Retrospective case series. SETTING:
      University Teaching Hospital. METHODS: The case notes of 9 patients with
      diagnosis of mucormycosis who presented from 1973 to 2001 were examined. The data
      for predisposing factors, signs/symptoms, histological diagnosis, radiological
      intervention, medical and surgical treatment and final outcome was analysed.
      RESULTS: There were 9 patients with mucormycoses. Early diagnosis was made by
      endoscopic examination and frozen section in 5 patients, which was later
      confirmed by histology. Treatment included parental and/or local amphotericin,
      hyperbaric oxygen and debridement either by endoscopic or external approach, with
      or without orbital exenteration. This resulted in an overall survival of 5
      patients. CONCLUSION: Frozen section diagnosis allows for early therapy since
      successful treatment depends on systemic amphotericin, surgical debridement and
      treatment of underlying predisposing factors. Nasal endoscopy is useful in
      diagnosis, endoscopic debridement and follow up of patients.

PMID- 15462175
TI  - [Sphenochoanal polyp: report of two cases].
AB  - OBJECTIVE: Report of 2 cases of sphenochoanal polyp. MATERIAL AND METHOD: We
      present two cases of sphenochoanal polyp aged of 22 and 53. They were operated by
      endonasal endoscopic approach. They are still free of symptoms and no recurrence
      are observed after 13 and 56 months of follow-up. CONCLUSION: The clinical,
      radiological and pathological features of the sphenochoanal polyp are reviewed.
      Different etiopathogenic hypothesis are discussed and particular the
      gastroesophageal reflux. The treatment is surgical.

PMID- 15462176
TI  - Monoamine oxidase inhibitors, their structural analogues, and neuroprotection.
AB  - Monoamine oxidase (MAO) inhibitors have been used for many years in the treatment
      of psychiatric and neurological disorders. More recently, some of these drugs and
      their analogues have been shown to have neuroprotective and neurorescue effects
      in several models of neurologic insult, including in vitro and in vivo models of
      cerebral ischemia. This review will discuss current evidence regarding these
      aspects of l-deprenyl, tranylcypromine, phenelzine, and some structurally related
      drugs.

PMID- 15462177
TI  - Development of preincubated chicken eggs following exposure to 50 Hz
      electromagnetic fields with 1.33-7.32 mT flux densities.
AB  - The effects of applying extremely low-frequency (50 Hz) electromagnetic fields
      (ELF-EMF) for 24 hr and different densities (1.33-7.32 mT) were examined on
      healthy, freshly fertilized white leghorn chicken eggs (55-65 g). Results showed
      no increase in the rate of abnormalities in exposed groups, but were only
      significant in 4.19, 5.32 and 5.86, 6.65 mT densities. Alizarin red S and alcian
      blue 8GX staining showed some embryos with extra ribs, defects in ribs and
      vertebrae, anuria and abnormal beaks. Study of egg weight, after 9 days of
      incubation, showed no significant differences between control, sham-exposed and
      experimental groups. Analysis of crown-rump, beak-occipital length and weight of
      embryo, showed significant decrease in weight at 4.39 and 5.52 mT intensities,
      comparing with control and sham-exposed groups. These results revealed that 50 Hz
      electromagnetic fields can even induce developmental alterations in preincubated
      chick embryos and confirm that its strength could be a determinant factor for the
      embryonic response to extremely low frequency EMFs (window effects) prior to
      incubation.

PMID- 15462178
TI  - Effect of low-power helium-neon laser irradiation on 13-week immobilized
      articular cartilage of rabbits.
AB  - Influence of low-power (632.8 nm, Helium-Neon, 13 J/cm2, three times a week)
      laser on 13-week immobilized articular cartilage was examined with rabbits knee
      model. Number of chondrocytes and depth of articular cartilage of experimental
      group were significantly higher than those of sham irradiated group. Surface
      morphology of sham-irradiated group had rough prominences, fibrillation and
      lacunae but surface morphology of experimental group had more similarities to
      control group than to sham irradiated group. There were marked differences
      between ultrastructure features of control group and experimental group in
      comparison with sham irradiated group. Low-power Helium-Neon laser irradiation on
      13-week immobilized knee joints of rabbits neutrilized adverse effects of
      immobilization on articular cartilage.

PMID- 15462179
TI  - Vitamin E prevents deleterious effects of di (2-ethyl hexyl) phthalate, a
      plasticizer used in PVC blood storage bags.
AB  - Vitamin E administration prevented DEHP induced deleterious effects like (i)
      degenerative changes in the brain and thyroid, (ii) decrease in the activity of
      neuronal membrane Na+ - K+ ATPase, (iii) decrease in the concentration of
      insulin, cortisol and TSH, and (iv) the increase in T3 and T4 in female Albino
      rats. The results suggest use of vitamin E to prevent harmful effects of repeated
      transfusion of DEHP containing blood as in thalassemia patient. The possibility
      of using vitamin E to prevent the harmful effects of repeated transfusion of DEHP
      containing blood, as in thalassemia patients, is discussed.

PMID- 15462180
TI  - Effectiveness of ethylene glycol bis (2-aminoethyl ether) tetraacetic acid (EGTA)
      against cerium toxicity.
AB  - Therapeutic efficacy of EGTA (ethylene glycol bis (2-aminoethyl ether)
      tetraacetic acid) against cerium intoxicated mice was studied. Administration of
      cerium showed significant decrease in haemoglobin percentage, RBC counts and
      blood glucose level with an increase in the activity of serum transaminases and
      WBC counts. Decrease in the activity of alkaline phosphatase and glycogen content
      was noted in liver and kidney after cerium exposure. Light and electron
      microscopical investigations showed that these changes were recouped considerably
      with the administration of EGTA suggesting its therapeutic efficacy against
      cerium toxicity.

PMID- 15462182
TI  - Evaluation of antimitotic activity of Rotula aquatica (Lour): a traditional herb
      used in treatment of cancer.
AB  - Rotula aquatica was extensively used by vaidyas (Ayurvedic practioners) in
      holistic treatment of cancer. In the present study, an attempt has been made to
      evaluate the antimitotic activity of R. aquatica. Preliminary antimitotic
      screening was done using Allium cepa root tip assay. The mitotic index of the
      root tips markedly decreased with increasing concentration of the aqueous
      extract. The different fractions obtained by successive extraction of R. aquatica
      using solvents of increasing polarity were also evaluated for their antimitotic
      activity. Tannins were isolated which showed a better activity than the non
      tannin fraction. Experiments were also carried out with incorporation of folic
      acid in the aqueous extract. Folic acid inhibited the antimitotic activity of
      aqueous extract of R. aquatica in a dose dependent manner. The results obtained
      were compared with methotrexate--a known drug available in market as anti-cancer
      agent. The studies were extended to human cells using 3 pancreatic cancer cell
      lines, viz: HPAF-II, BxPC-3, and CAPAN-2. Extract of R. aquatica was found to be
      extremely effective in the prevention of cell proliferation of the pancreatic
      cancer cell lines. The phytochemical evaluation revealed presence of polyphenols
      (tannins) and steroids. A HPTLC fingerprinting was developed and studied. Two
      compounds were isolated and subjected to spectral studies like UV, IR and mass
      spectrums. The empirical formula was derived by considering this data with
      elemental analysis of the compounds.

PMID- 15462181
TI  - Oxyradicals under UV-b stress and their quenching by antioxidants.
AB  - Formation of oxyradicals under UV-B stress was investigated using cucumber
      cotyledons. UV-B radiation induced production of free radicals which were
      analyzed by ESR spectroscopy. Evidence was obtained for the formation of
      superoxide and hydroxyl radicals in the tissues by comparing PBN-adducts formed
      with radicals obtained by chemical autooxidation of KO2 and Fenton's reaction.
      Addition of superoxide dismutase (SOD) to the reaction mixture partially reduced
      the intensity of signals confirming the production of superoxide radical as well
      as hydroxyl radicals. These radicals were quenched in vitro by the natural
      antioxidants alpha-tocopherol, ascorbic acid and benzoquinone. Changes in the
      level of antioxidants were also monitored under UV-B stress. The endogenous level
      of ascorbic acid was enhanced and alpha-tocopherol level was reduced in the
      tissue after exposure to UV-B radiation. The present report happens to be the
      first direct evidence obtained for the formation of superoxide and hydroxyl
      radicals in plant tissues exposed to UV-B radiation.

PMID- 15462183
TI  - Dietary intervention with iron and black tea infusion in reducing cytotoxicity of
      arsenic.
AB  - The relative efficacy of infusion of black tea leaf, Camellia sinensis (Linn.) O.
      Kuntze, (Theaceae), and iron as freshly prepared aqueous solution of ferrous
      sulphate in reducing the cytotoxic effects of arsenic, was tested in bone marrow
      cells of laboratory bred Swiss albino mice. Ferrous sulphate and tea given alone
      did not induce chromosomal breakage to any appreciable extent. Tea decreased
      chromosome damage induced by arsenic to a significant extent, while the addition
      of ferrous sulphate did not alter the protective action of tea against arsenic.
      Such protection against arsenic cytotoxicity by prolonged dietary administration
      of black tea infusion--a common routine beverage--is of importance in view of
      widespread exposure of human populations to arsenic damage through drinking water
      from tubewells in Eastern India and Bangladesh.

PMID- 15462184
TI  - Hypocholesterolemic effect of protein prepared from Phaseolus aconitifolius
      (Jacq.).
AB  - Hypocholesterolemic effect of protein concentrate (PC) prepared from moth bean
      (Phaseolus aconitifolius Jacq.) seeds relative to that of pigeon pea PC and
      casein were investigated in rats fed on hypercholesterolemic diet containing two
      per cent cholesterol. The test diets containing casein and legume PCs at 10%
      protein level were fed to albino rats (Wistar strain) for 45 days. Compared to
      casein, the two legume PCs produced significantly lower levels of liver total
      lipid and cholesterol levels except that pigeon pea PC produced only non
      significant decrease of total cholesterols in the heart. In addition, the legume
      PCs produced significantly lower levels of serum triglycerides and total lipids
      as well as lower levels of total and low-density lipoprotein cholesterol.
      Moreover, only moth bean PC produced a significantly higher level of serum high
      density lipoprotein cholesterol. Generally, PC of moth bean seemed to be more
      potent at lowering the elevated hepatic and serum lipids and cholesterol levels,
      which were attributed to the amino acid profile of this lesser-known legume as
      these indices well correlated with serum cholesterol levels.

PMID- 15462185
TI  - Hypolipidemic effect of Coriandrum sativum L. in triton-induced hyperlipidemic
      rats.
AB  - In the biphasic model of triton-induced hyperlipidemia, C. sativum at a dose of
      1g/kg body weight reduced cholesterol and triglycerides levels in both synthesis
      and excretory phases in rats, and the results were comparable with that of
      Liponil, a commercially available herbal hypolipidemic drug. The results suggest
      that coriander decreases the uptake and enhances the breakdown of lipids. From
      the study it can be assumed that coriander has the potential to be popularized as
      a household herbal remedy with preventive and curative effect against
      hyperlipidemia.

PMID- 15462186
TI  - Evaluation of tocolytic efficacy of selective beta2 adrenoceptor agonists on
      buffalo uterus.
AB  - Present study was conducted on prostaglandin F2alpha (PGF2alpha), oxytocin, (OT),
      potassium chloride (KCI) and barium chloride (BaCl2) pre-contracted perimetrial
      uterine strips of dioestrus and pregnant buffaloes to evaluate the tocolytic
      efficacy of selective beta2 adrenoceptor agonists-albuterol (salbutamol) and
      terbutaline. Cumulative concentration-response curves of both the beta2
      adrenoceptor agonists were constructed and the mean effective concentration
      (EC50) values determined and compared statistically. Based on the comparative
      EC50 values in relaxing the pre-contracted uterine strips with different
      spasmogens, the rank order potency of albuterol was found to be--PGF2alpha >
      BaCl2 > OT > KCl on uterine strips from dioestrus animals, while OT> BaCl2>
      PGF2alpha >KCl on the uterine strips of pregnant buffaloes. The rank order
      potency of terbutaline on uterine strips from dioestrus stage animals was- BaCl2
      > OT > KCl > PGF2alpha, while BaCl2 > PGF2alpha > KCl > OT on uterine tissues of
      pregnant animals. Thus, irrespective of the state of uterus, whether gravid or
      non-gravid, KCl-depolarized uterine tissues required comparatively higher
      concentrations of albuterol or terbutaline to produce tocolytic effect. High
      concentrations of K+ in biophase may have interfered with the beta2 adrenoceptor
      agonists-induced outward K+ current and hyperpolarization. From the results of
      present study, it was evident that selective beta2 adrenergic agonists had good
      tocolytic efficacy on the uterus of buffaloes. Further, indirectly the
      possibility of existence and activation of K(Ca) channels by selective beta2
      adrenoceptor agonists in mediating tocolysis of buffalo myometrium can not be
      ruled out, however, detailed studies using specific K(Ca) channel blockers are
      required for characterizing the nature of such channels in buffalo uterus.

PMID- 15462187
TI  - Ondansetron amelioration of scopolamine induced cognitive deficits in three-panel
      runway apparatus in rats.
AB  - Effect of ondansetron (5-HT3-receptor antagonist) was studied on the working
      memory deficits induced by scopolamine, a muscarinic receptor antagonist in rats
      using a three-panel runway apparatus. Varying doses of scopolamine (0.1
      0.56mg/kg, ip) were administered alone or in combination with ondansetron (0.01
      1.0 mg/kg, ip) and memory errors and latency period of the session were recorded
      on a three-panel runway apparatus. Treatment with scopolamine (0.56 mg/kg)
      produced working memory deficits in rats. Treatment with ondansetron (1.0 mg/kg)
      significantly reduced the scopolamine-induced working memory deficits.

PMID- 15462188
TI  - In vitro and in vivo antimycobacterial activity of antiinflammatory drug,
      diclofenac sodium.
AB  - The non-steroidal antiinflammatory drug diclofenac sodium exhibited remarkable
      inhibitory action against both drug sensitive and drug resistant clinical
      isolates of Mycobacterium tuberculosis, as well as other mycobacteria. This agent
      was tested in vitro against 45 different strains of mycobacteria, most of which
      were inhibited by the drug at 10-25 microg/ml concentration. When tested in vivo,
      diclofenac, injected at 10 mg/kg body weight of a Swiss strain of white mice,
      could significantly protect them when challenged with a 50 median lethal dose of
      M. tuberculosis H37 Rv102. According to Chi-square test, the in vivo data were
      highly significant (P<0.01).

PMID- 15462189
TI  - Isolation, characterization and optimization of antifungal activity of an
      actinomycete of soil origin.
AB  - About 312 actinomycetes were isolated from soil samples on chitin agar. All these
      isolates were purified and screened for their antifungal activity against
      pathogenic fungi. Out of these, 22% of the isolates exhibited activity against
      fungi. One promising isolate with strong antifungal activity against pathogenic
      fungi was selected for further studies. This isolate was from Pune, and was
      active against both yeasts and molds. Various fermentation parameters were
      optimized. Based on morphological and biochemical parameters, the isolate was
      identified as Streptomyces. The correlation of antifungal activity with growth
      indicated growth dependent production of antimetabolite. Maximum antifungal
      metabolite production (600 units/ml) was achieved in the late log phase, which
      remained constant during stationery phase, and it was extracellular in nature.

PMID- 15462190
TI  - Isolation of Mycoplasma bovoculi from genitally diseased bovines and its
      experimental pathogenicity in pregnant guinea pigs.
AB  - Thirteen strains of M. bovoculi, 6 from frozen bull-semen (3.5% of 168), 3 from
      neat bull-semen (3.0% of 100), one each from heart blood and stomach contents of
      aborted foetus of 85 (1.18%) bovine-abortions, one each from stomach contents and
      pooled internal organs of 9 (11.1%) stillborn calves, were isolated. All the
      isolates were resistant to ampicillin and sensitive to spiramycin, vibramycin,
      demeclocyclin, oxytetracycline, lincomycin and tylosin. However, variation in
      resistance to tetracycline, erythromycin, neomycin, kanamycin and streptomycin
      was observed. The gross lesions like congestion of lungs, liver, kidney and
      spleen were noted only in stillborn calf. However, significant microscopic
      lesions were encountered in internal tissues of both the aborted bovine fetuses
      and stillborn calf. Thickened alveolar wall, congestion of blood vessels,
      mesenchymal cell proliferation along with infiltration of lymphocytes and
      macrophages were observed in lungs. The liver showed mild infiltration of
      lymphocytes, macrophages in hepatic triad and necrosis of hepatic cells. The
      kidney tissues had focal lymphocytic infiltration in the interstitium. One strain
      of M. bovoculi (isolate # SBC-7/84,IO) isolated from a stillborn calf was found
      abortigenic upon experimental inoculation in pregnant guinea pigs.

PMID- 15462191
TI  - (CTG)n expansion at DMPK locus seen only in muscle tissue: a novel case.
AB  - Triplet repeat expansion in 3 untranslated region of myotonic dystrophy protein
      kinase (DMPK) gene has been implicated as causative in myotonic dystrophy (DM).
      In cases of DM, high levels of somatic instability have been reported, in which
      inter-tissue repeat length differences as large as 3000 repeats have been
      observed. This study highlights the inter-tissue (CTG)n expansion variability at
      the DMPK locus. Molecular analysis of DMPK gene, encompassing the triplet repeat
      expansion, was carried out in 31 individuals (11 clinically identified DM
      patients, 20 controls). All controls showed a 2.1kb band (upto 35 CTG repeats),
      while four cases exhibited an expansion (>50 repeats). A novel observation was
      made in one case, wherein the DNA from lymphocytes showed a normal 2.1kb band
      while the muscle tissue DNA from the same patient was heterozygous for normal and
      4.3 kb band (>700 repeats). Our results suggested that because inter-tissue
      variability existed in the (CTG)n repeat number at DMPK locus, an attempt should
      be made to evaluate affected tissue along with blood wherever possible prior to
      making a final diagnosis. This is important not only for diagnosis and prenatal
      analysis, but also while providing genetic counseling to families.

PMID- 15462192
TI  - Effect of chlorpromazine, imipramine and lithium on MAO-A and MAO-B activity in
      rat brain mitochondria.
AB  - Drugs with efficacy in psychiatric disorders affect the function of central
      neurotransmitter amines, which are inactivated primarily by monoamine oxidase
      (MAO). Effect of these drugs on the two types of MAO (MAO-A and MAO-B) has been
      studied in rat brain. The result showed that chlorpromazine (CPZ) and imipramine
      (IMI) at concentrations of 1x10(-2), 5x10(-3) and 2.5x10(-3) M inhibited rat
      brain mitochondrial MAO-A activity in vitro by 82, 50, 39 and 86, 74, 38 %,
      respectively. CPZ at concentrations of 5x10(-3), 2.5x10(-3), 1x10(-3) M inhibited
      rat brain mitochondrial MAO-B activity in vitro by 83, 55, 39 %, respectively,
      while IMI at concentrations of 5x10(-4), 2.5x10(-4), 1x10(-4) M inhibited the in
      vitro enzyme activity by 43, 35, 21 %, respectively. Lithium at concentration of
      5x10(-3) M could not either inhibit MAO-A or MAO-B in the mitochondrial fraction
      of rat brain.

PMID- 15462193
TI  - [Genomic, molecular biology and malaria: new medical perspectives?].
AB  - The knowledge of genomic structure of man, of Plasmodium falciparum and of its
      main vector Anopheles gambiae has led to great progress in the understanding of
      malaria pathophysiology. It may also offer new perspectives for malaria therapy
      vaccines or control of mosquito-borne transmission. In pathophysiology, genes
      encoding adhesion plasmodial proteins of their receptors were identified, as well
      as other genes controlling the patient immune response or the antigenic parasite
      variability. From a therapeutic point of view, new targets for future
      antimalarial drugs were identified, mainly in apicoplast (a vestige of vegetal
      structure incorporated by the parasite during its phylogenic evolution) and
      several enzymes, particularly proteases. It will be now necessary among these
      "promising new molecules" to select a few ones (probably no more than 5 or 6) for
      a pre clinical and clinical pharmaceutical development. Indeed, the industrial
      possibilities for developing new antimalarial drugs are evidently limited and
      several other antimalarial drugs are already under development. For future
      malaria vaccines, several new targets and antigenic proteins were also
      identified. As for new drugs, a complete evaluation of these antigens is
      absolutely necessary to select few of them for clinical development. Particularly
      for malaria, ADN vaccines may offer very promising perspectives with the
      possibility to obtain both humoral and cellular immunity and to use at the same
      time a panel of plasmodial antigens. It could be thus possible to obtain a
      simultaneous immunization against different stages of Plasmodium falciparum
      (sporozoites, merozoites, gametocytes) and to use, as an adjuvant, a gene
      encoding a viral protein or a cytokine (GMCSF). In Anopheles gambiae genome,
      several genes encoding for key-proteins, particularly odorant receptors necessary
      for blood meals, were identified. Non biting-non transmitting mosquitoes were
      obtained by genetic manipulation and, from an academic viewpoint, offer a very
      attractive new perspective for the interruption of malaria transmission.
      Unfortunately several practical problems remain unsolved and genetically modified
      mosquitoes do not survive long enough among "wild" strains. On the whole genomic
      and proteomic gave very exciting scientific results in malaria and, very probably
      the post-genomic phase will even give more new data. From a practical, medical
      viewpoint, it is still too early and speculative to imagine their possible
      applications for malaria control.

PMID- 15462194
TI  - [Study of antigen HBs and antivirus antibodies of hepatitis C during
      hepatopathies in Mali].
AB  - A prospective study carried out in Bamako, Mali between July 1998 and January
      1999 has assessed the seroprevalence of hepatitis C virus (HCV) in 91 carrier
      patients of chronic hepatopathy at a cirrhrosis stage (53) or of hepato-cellular
      carcinoma (38) and to compare with in 92 blood donors as a control population.
      Only seroprevalence confirmed by a complementary test has been taken into account
      (RIBA). HCV seroprevalence reached 25% including all hepatopathies, 24% in
      cirrhrosis and 26% in hepato-cellular carcinomae (HCC) versus 4% in blood donors.
      Antigen HBs of hepatitis B virus has been found in 55% of patients, versus 25% of
      the control cases (p = 0.0006). On the whole, the two markers have been notified
      a little more often in HCC than in cirrhosis and the combination of the two
      markers has been more frequent during cirrhosis as well. The role of HCV played
      in cirrhosis and HCC onset in Mali appears to be important.

PMID- 15462195
TI  - [Prevalence of hepatitis A, B, C and E virus markers among patients with elevated
      levels of Alanine aminotransferase and Aspartate aminotransferase in Phnom Penh
      (Cambodia) and Nha Trang (Central Vietnam)].
AB  - In order to describe the respective part of viral hepatitis in liver diseases
      observed in Cambodia and Vietnam, ninety consecutive patients with Aspartate
      aminotransferase (AST) and Alanine aminotransferase (ALT) > or = 100 Ul/l were
      tested for hepatitis A, B, C and E markers in Phnom Penh and Nha Trang. The
      markers were IgM antibodies to hepatitis A virus (anti-HAV IgM), hepatitis B
      surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCVAb) and IgG
      antibodies to hepatitis E virus (anti-HEV IgG). Recruited patients were
      predominantly adults and male (sex ratio 76%). Among these patients, 81% were
      tested positive to at least one marker in Nha Trang and 79% in Phnom Penh. In Nha
      Trang, HBsAg was more frequent (73%) than anti-HCV Ab (9%) while in Phnom Penh
      both markers were closely similar (HBsAg: 41%, anti-HCV Ab: 39%). In both
      population samples, HBsAg was more prevalent among young people whereas anti-HCV
      Ab were only detected in adults. No case of acute HAV infection was diagnosed in
      Nha Trang while anti-HAV IgM were detected in 20% of Cambodian patients. Anti-HEV
      IgG were infrequent (2% in Nha Trang, 5.5% in Phnom Penh). Only one case was
      notified, a male Vietnamese patient probably suffering from acute hepatitis E.
      More studies would be useful to improve the control measures against viral
      hepatitis in the public health programs.

PMID- 15462196
TI  - [Contribution of phage typing and ribotyping in investigating a typhoid fever
      outbreak in Tunisia].
AB  - A study was carried out to investigate an outbreak of typhoid fever that occurred
      in Sousse city and in the vicinity of Sousse (Tunisia) during summer 1999. Twenty
      four isolates of Salmonella enterica serotype Typhi were isolated in hospitalized
      patients with a typhoid fever in two hospitals (Farhat Hached Sousse and M'saken)
      and were studied with the help of two molecular typing methods: phage typing and
      automated ribotyping. Twenty one isolates with the Vi antigen had profile DVS
      (Degraded Vi Strain), one isolate with the Vi antigen belonged to phage type A
      and two isolates were non phage typable (no Vi antigen). The same ribotype was
      found in 22 out of 24 isolates. The results suggested that ribotyping is more
      discriminative than phage typing in this case in distinguishing strains and the
      strains shared the same source of the contamination. Unfortunately the precise
      source of the contamination could not be determined.

PMID- 15462197
TI  - [Major hypoglycemia during malaria outburst treated by quinine: importance of
      glucagon].
AB  - An efficient quinine therapy administered for the treatment of severe malaria has
      induced a major hypoglycemia in a pregnant woman. Glycemia varied from 0.3 to 0.6
      g/l (normal: 0.7-1.1 g/l) despite symptoms correction by infusion of 2.51 of
      hypertonic glucose serum at 30% per day. The continuous infusion of glucagon: 1
      mg diluted in 50 cm3 of physiological saline solution, at 0.5 to 6 ml/h rate has
      allowed a normal glycemia value and quinine therapy was carried on until the 7th
      day.

PMID- 15462198
TI  - [Therapeutic efficiency of chloroquine in the savannah region in the north of
      Cote d'Ivoire (1997)].
AB  - We evaluated from August to December 1997 the therapeutic effect of chloroquine
      (CQ) in treatment of mild malaria. Five villages of the savannah area of Cote
      d'Ivoire were selected for this study In this area and season, the transmission
      of malaria is of hyper-endemic type. The 14-day protocol of WHO was used and all
      the patients were treated with CQ 25 mg/kg over three days. 360 febrile children
      between 6 and 83 months old out of 545 were selected, and 286 were fully
      followed. At the beginning of the study axillary temperatures and parasitemia
      showed no difference in the 5 villages. The average therapy failure rate was
      11.5% (IC to 95%; 7.8-15.2) with a maximum of 18.5%. The failure rates estimated
      in the various villages showed a hardly significant difference (p = 0.05). In the
      North of Cote d'Ivoire, the good efficiency of CQ can be explained by the low
      drugs pressure related to the behaviour of populations who use traditional
      phytotherapy in first resort to treat the fevers.

PMID- 15462199
TI  - [In vivo evaluation of sulfadoxine-pyrimethamine efficacy during uncomplicated
      falciparum malaria in children of Yopougon (Abidjan, Cote d'Ivoire)].
AB  - The malaria, deadly parasite infection in its severe form, is widely spread in
      tropical zone where it rages in an endemic way. The emergence and the extension
      of Plasmodium resistance contributed to increase the morbidity and the mortality
      of this pathology in children under 5 years old. Facing the extend of this
      phenomenon, a monitoring of the expansion of the chemosensitivity proves to be
      necessary. The goal of the present study was to assess the sulfadoxine
      pyrimethamine (S-P) efficacy according to the in vivo test WHO protocol of 14
      days-follow-up. Children are treated to the S-P at the rate of 1/2 tablet per 10
      kg of body weight in unique dose, then controls are done days 3, 7 and 14. At the
      end of this work, 179 on 475 subjects were effectively carriers of asexual
      parasites. So, the general plasmodic index and Plasmodium falciparum rate
      infection were respectively 37.7% and 100%. Among the 89 children followed until
      J14, those aged of 13 to 24 months represented 38% of the population of children
      suffering from Plasmodium malaria, against 7% of those aged between 49 and 59
      months. In terms of therapeutic efficacy, 76.4% of adequate clinical and
      parasitological response (ACR) have been reached against 23.6% of therapeutic
      failure (TF).

PMID- 15462200
TI  - [Outbreak of meningitis in the province of Logone occidental (Chad): descriptive
      study using health ministry data from 1998 to 2001].
AB  - Outbreaks of meningitis are a public health problem in sub-Saharan Africa where
      more than thousand cases are declared every year In Chad, the last outbreak
      happened between 1998 and 2001. The objective of this study is to describe
      epidemiologic profile of meningitis in the province of Logone Occidental from
      1998 to 2001. METHODS: Study used epidemiologic data of surveillance's tools from
      years 1998 to 2001 in Chad. RESULTS: Data of the study indicated a two-yearly
      cycle with outbreaks in 1998 and 2000 occurring in endemic background during 1999
      and 2001. The first cases began in January with an incidence rate close to 30 for
      100.000/week. The epidemic peak occurred on the 11th week (1999-2001), on the
      12th week (1998-2000) during dry season. Outbreak continued 9 weeks and stopped
      on the 16th week (April-May). The lethality average was 12% and reached 30% at
      the beginning of the outbreak. DISCUSSION: Despite vaccination campaigns during
      outbreaks, epidemiology did not change in Chad. Quality of epidemiological
      surveillance is not sufficient and political reaction is too slow. Moreover,
      human, material and financial deficiency add to these difficulties. Integrated
      vaccination against meningitis into the immunization preventive program was
      evocated but would not permit enough collective immunity. Biotope changes
      generated by human activity could contribute to perpetuating outbreaks. New
      outbreak of W135 meningitis in Burkina Faso (2002) may change the epidemiological
      profile of the meningitis in sub-Saharan Africa. CONCLUSION: Meningitis outbreaks
      control using vaccination after the first cases appears to be limited, however
      this strategy must be evaluated in Chad to know vaccination covering, target
      population and protection after vaccination.

PMID- 15462201
TI  - [Chagas disease in a rural area of Northeast Brazil].
AB  - A serological and medical survey on Chagas disease was carried out between
      December 1997 and June 2000 in four villages of the semi-arid rural Northeast
      Brazil. The average human serological prevalence rate of 11.8% was strongly
      linked with age: 1.1% for people under 25, 13.7% for people aged of 26 to 49,
      29.5% for people aged of 50+. The clinical form was indeterminate for 57% of the
      infected population, cardiac for 35%, digestive or mixed for 8%. The infected
      patients under 55 received at home an etiologic treatment with benznidazol. The
      survey confirms the drastic reduction of Trypanosoma cruzi transmission during
      the last decades, especially since 25 years. This situation is the result jointly
      of the antivectorial activities, improvement of education level and changes in
      the way of life. However Chagas disease is still a serious problem, especially
      for numerous middle-aged infected adults. The situation could be improved by
      increasing the serologic screening in the field as well as the counselling and
      the treatment of the patients.

PMID- 15462202
TI  - [Rickettsia africae, the agent of African tick-bite fever: an emerging pathogen
      in the West Indies and Reunion Island (Indian Ocean)].
AB  - Rickettsia africae is the agent of African tick bite fever, an emerging disease
      transmitted by Amblyomma ticks in sub-Saharan Africa. In 1998, we reported the
      first documented case of R. africae in the New World, in a patient who had
      returned from Guadeloupe. In order to confirm the presence of R. africae in the
      West Indies, entomologic surveys were conducted from 1999 to 2003 to collect
      Amblyomma, which are considered as potential vectors and reservoirs of the
      bacteria. Ticks were used as epidemiological tools to detect R. africae by
      molecular tools and/or cultivate the bacteria in shell-vial cell culture. This
      paper summarizes the results obtained in the West Indies. R. africae was detected
      and isolated for the first time in Guadeloupe, and then detected by molecular
      tools in Martinique and St-Kitts and Nevis. These last results confirm our first
      hypotheses--that is R. africae is prevalent on all the Caribbean islands where A.
      variegatum ticks have been introduced from Africa in the 18th and 19th centuries.
      We also present the results of a study conducted on the Reunion Island, a French
      island in the Indian Ocean. For the first time there, R. africae was detected in
      A. variegatum ticks, which were probably introduced from the African mainland or
      Madagascar with the human colonization during the 17th century Thus, clinicians
      should be aware that patient presenting in the West Indies or on Reunion Island
      (or after a trip over there) with fever, eschar (often multiple), regional
      lymphadenopathy and a rash, might be infected by R. africae.

PMID- 15462203
TI  - [Epidemics of Ebola haemorrhagic fever in Gabon (1994-2002). Epidemiologic
      aspects and considerations on control measures].
AB  - Based on the description of the four Ebola haemorrhagic fever epidemics (EHF)
      occurred in Gabon between 1994 and 2002, the authors are considering the cultural
      and psycho-sociological aspects accounting for the difficulty to implement
      control measures. On the whole, the result of these raging epidemics came up to
      207 cases and 150 dead (lethality: 72%). Analysing precisely the aspects of the
      third epidemic and pointing up the possible factors explaining its spreading far
      beyond its epicentre, the authors bring about the limits of measures not always
      understood by local populations. The discussion will deal with the possibilities
      of a better surveillance, a quick management of intervention means including a
      regional permanent pre-alert and taking into account the issue raised by the
      possible Ebola virus endemic.

PMID- 15462204
TI  - [Bacterial and viral epidemics of zoonotic origin; the role of hunting and
      cutting up wild animals].
AB  - Since the Prehistoric times hunting has been a vital activity for man. However,
      this may account for the contamination of the hunter, his family and relatives.
      Infections may occur by direct contact with blood or tissues of infected animal
      during handling and cutting up preys and when preparing or eating meat, or also
      when bitten by injured animal. Apes and antelopes hunting in sub-Saharan Africa
      proves to be particularly important since it has been well established that the
      recent or previous emergence of some viral zoonosis (Ebola, Aids, T lymphotropic
      viruses and Monkeypox) resulted from hunting and poaching. Moreover predation
      among different species of non human primates such as that practised by
      chimpanzees against monkeys, has led to the construction of recombinant simian
      Lentiviruses, such as SIV cpz able to infect man and then spread over the entire
      mankind as it was the case with HIV-1. SARS is another possible example of the
      zoonotic risks represented by the sale, handling and cutting up Chinese wild
      animals such as Himalayan civets for culinary purposes.

PMID- 15462205
TI  - [Dopamine synthesis by non-dopaminergic neurons of the rat fetus arquate
      nucleus].
AB  - Our hypothesis was tested in respect to dopamine synthesis by non-dopaminergic
      neurons expressing individual complementary enzymes of the DA synthetic pathway.
      According to the hypothesis, L-dihydroxyphenylalanine (L-DOPA) synthesised in
      tyrosine hydroxylase(TH)-expressing neurons for conversion to dopamine. The
      mediobasal hypothalamus of rats on the 21st embryonic day was used as an
      experimental model. The fetal substantia nigra containing dopaminergic neurons
      served as control. Dopamine and L-DOPA were measured by high performance liquid
      chromatography in cell extracts and incubation medium in presence or absence of L
      tyrosine. L-tyrosine administration increased L-DOPA synthesis in the mediobasal
      hypothalamus and substantia nigra. Moreover, L-tyrosine provoked an increase of
      dopamine synthesis in substantia nigra and a decrease in the mediobasal
      hypothalamus. This is, probably, due to an L-tyrosine-induced competitive
      inhibition of the L-DOPA transport to monoenzymatic AADC neurons after its
      release from the monoenzymatic TH neurons. This study provides a convincing
      evidence of dopamine synthesis by non-dopaminergic neurons expressing TH or AADC,
      in cooperation.

PMID- 15462206
TI  - [Tetrodotoxine-dependent glycine release in the rat nucleus accumbens during
      correction of feeding behaviour].
AB  - Presence of a tone previously paired with a foot-shock in rats during food intake
      increases the glycine extracellular level in the n. accumbens. The increase will
      be completely prevented by intra-accumbal infusion of Na-channel blocking agent
      tetrodotoxine. The findings suggest that glycine mechanisms in the n. accumbens
      are involved in the correction of feeding behaviour.

PMID- 15462207
TI  - [Peculiarities of interhemisphere interaction at different levels of
      consciousness].
AB  - Transition from wakefulness to drowsiness was used as a model of a gradual
      decrease in the consciousness level. Subjects' self-reported changes in the
      contents of consciousness, namely: the intensity and quality of involuntary
      mental processes, served as an indicator of the consciousness level. Each
      observed level of consciousness was shown to be characterised by a certain EEG
      profile. It was also shown that the state in which the subject signals of a
      slowdown of the "internal speech" or the "lapse of thoughts" corresponds to the
      lowest level of activation. In this case, the interhemisphere connections
      involving the main mechanism of cognitive information transmission, i.e. the EEG
      high-frequency rhythms, becomes suppressed.

PMID- 15462208
TI  - [The long-term memory retrieval following kainic acid administration].
AB  - Effect of the neurotoxin kainic acid to the food-procuring task were studied in
      Wistar rats. A single injection of the acid in subconvulsive dose (8 mg/kg)
      impaired the task performance within some weeks but not immediately after the
      treatment. Higher doses of kainic acid (10 mg/kg) impaired the task performance
      within a few hours after treatment for up to 10 days. The treatment did not
      prevent rat's learning of a new task in the same experimental chamber. The
      revealed deficit in the long-term memory retrieval might be explained by specific
      effects of kainic acid upon the hippocampal system.

PMID- 15462209
TI  - [Analysis of spontaneous unit activity of the lateral vestibular nucleus' neurons
      in norm and after effects of vibration].
AB  - Changes of spontaneous unit activity in the lateral vestibular nucleus of the rat
      following 5-, 10- and 15-day vibration (60 Hz, 2 hrs. Daily), were studied.
      Averaged histogramz and autocorrelograms were analysed following computerized
      interspike intervals. The data obtained revealed a variety of the unit activity
      in its direct or mediated effects exerted through several structures of the
      central nervous system.

PMID- 15462210
TI  - [Water permeability of the OMCD and IMCD cells' basolateral membrane under the
      conditions of dehydration and dDAVP action].
AB  - Water permeability of the basolateral membrane was estimated in isolated
      fragments of OMCD or IMCD in the Wistar rats. Apical surface of the fragments was
      blocked with oil injected into the lumen. Apparent water permeability coefficient
      (Pf) was measured by the rate of epithelium swelling following transition from
      hypertonic to isotonic medium (600 mOsm to 300 mOsm). Water deprivation caused
      significant increase in the Pf value in OMCD and IMCD fragments. Desmopressin
      (10(-8) M) increased water permeability in hydrated rats both in OMCD and IMCD.
      Mercury chloride decreased the Pf and abolished the effect of desmopressin in
      reversible manner. Estimation of aquaporins 2, 3, 4 mRNA content in the renal
      medulla was performed by semi-quantitative RT-PCR. Content of AQP4 and AQP2 mRNA
      in dehydrated animals was significantly higher than in hydrated ones both in
      outer medulla and inner medulla. Expression of AQP3 increased during dehydration
      only in the inner medulla. The findings reveal that water permeability of OMCD
      and IMCD can be increased by physiological stimuli, e.g. water deprivation. The
      activation of gene expression of the key elements of vasopressin signal system
      seems to contribute to this reaction.

PMID- 15462211
TI  - [The effect of various stage maturity of erythrocytes upon proliferatio rate of
      erythroid cells in "crown" of erythroblastic islands].
AB  - Joint cultivation of small amounts of young and mature erythrocytes with bone
      marrow erythroblastic islands during 24 hours in liquid culture system results in
      erythropoiesis stimulation due to increase of number of cells in the state of
      mitosis in island's "crown". Prolonged joint cultivation and/or joint cultivation
      with plenty of premature and mature erythrocytes leads to inhibition of the
      erythropoiesis in the state of mitosis in the island's "crown". The maximum of
      the inhibitory effect was shown by erythrocytes from polycythemia rats.

PMID- 15462212
TI  - [the effect of colonystimulating macrophage factor on activity of the nuclear
      organisers in central macrophages of the cultures of the bone marrow
      erythroblastic islands].
AB  - Erythroblastic islands of the bone marrow are morpho-functional units of
      erythropoiesis. The functional state of erythroblastic islands' cells of the bone
      marrow was for the first time defined by estimation of activity of the nuclear
      organisers of the central macrophages in the erythroblastic islands cultivated
      for 24 hrs in presence of various doses of the colony-stimulating macrophage
      factor. The findings indicate that increased doses of the colonystimulating
      macrophage factor was accompanied by a respective enhancement of the activity of
      nucleolar organisers in central macrophages of erythroblastic islands.

PMID- 15462213
TI  - [Some mechanisms of adenosine protective effect in the "calcium paradox"].
AB  - A possibility of preventing the "calcium paradox" with the aid of adenosine was
      studied as well as some mechanisms of adenosine effect upon the heart in case of
      the "calcium paradox". Adenosine was found to suppress release of amino acids
      from the heart in perfusion with calcium-free medium, to efficiently prevent
      disorders in the energy-dependent functions of mitochondrion and myoglobin
      release from the heart in reperfusion with Ca2+ -containing solution. Adenosine
      was also found to increase 2-10-fold lactate release from the heart. Adenosine
      seems to be able to activate glycolysis. Iodine acetate was shown to completely
      suppress the adenosine ability to decrease amino acid release from the heart
      perfused with calcium-free medium. Under conditions of iodine acetate blocking of
      glycolysis was found to possess no protective properties against cytolysis in the
      "calcium paradox". The heart mitochondria isolated in the end of the experiment
      revealed low values of free or phosphorylating respiration and complete
      dissociation of oxidation. Also a protective effect of adenosine in inhibition of
      Na+, K+ -ATPhase with Strophantinum, was studied.

PMID- 15462214
TI  - [Restoration of the heart activity in deep hypothermia with the aid of
      norepinephrine and no warming of the heart].
AB  - A possibility of restoration and stimulation of the rat isolated heart
      contractions in deep hypothermia by means of norepinephrine (6 microM) was
      studied. Following a complete arrest of the heart at a retrograde perfusion with
      the Krebs-Henseleit buffer ([K+] 5.9 mM), norepinephrine was found to restore the
      heart beats and to lower the heart arrest temperature from 8.2 +/- 0.5 degrees to
      6.6 +/- 0.3 degrees. At the perfusion with the Krebs-Henseleit buffer, the heart
      rate dropped to below 10 min(-1) at 13.0 +/- 0.9 degrees. Reduction of [K+] to
      2.95 mM intensified the heart rate. At a progressing cooling, the heart rate
      lower than 10 min(-1) occurred at 10.9 +/- 0.6 degrees. When adding
      norepinephrine (6 microM) to the perfusion fluid with [K+] 2.95 mM, the heart
      rate increased once again (on the average to 23.1 +/- 5.3 min(-1)) despite the
      fact that the heart temperature continued to be lowered. The heart rate lower
      than 10 min(-1) was reached at the progressing cooling to, on the average, 9.6 +/
      0.7 degrees. The findings show norepinephrine to exert a stimulating effect on
      the heart activity even at such low heart temperatures as 7-10 degrees with no
      preliminary warming of the heart.

PMID- 15462216
TI  - [Ivan Mikhailovich Sechenov (on the 175th anniversary) 1 (14) August 1829--2 (15)
      November 1905].

PMID- 15462215
TI  - [Effect of chronic administration of aminoguanidine on the reactivity of
      pulmonary vessels in rats with monocrotaline-induced pulmonary hypertension].
AB  - Monocrotaline (MCT)-induced pulmonary hepertension (PH) is associated with
      impaired endothelium-dependent relaxation and increased activity of inducible NO
      synthase (iNOS). To examine the role of iNOS in MCT-induced PH, we used iNOS
      inhibitor: aminoguanidine (AG). The PH was simulated with a subcutaneous
      injection of 60 mg/kg MCT to Wistar rats; control rats were injected with saline.
      Then each group was separated into 2 subgroups: the 1st one was given drinking
      water (MCT-C and C-C groups) whereas the 2nd one was given AG in drinking water
      (15 mg/(kg(-1) x day(-1)) (MCT-AG and C-AG groups). In 4 weeks, the perfusion
      pressure (PP) responses of isolated pulmonary arteries to acetylcholine (Ach) and
      activator of soluble guanylate cyclase (sGC), FPTO, were examined. In the MCT-C
      group, a decrease of relative PP to perfusion of 1 x 10(-8) M and 5 x 10(-8) M
      Ach and 1 x 10(-8) M FPTO was diminished. This reduction of relaxant responses in
      MCT-treated rats was prevented by AG treatment. The findings suggest that AG
      administration restores the impaired endothelium-dependent and sGC-dependent
      relaxation of the pulmonary artery at MCT-induced PH.

PMID- 15462217
TI  - [Academician Natalia Petrovna Bechtereva: a distinguished scientist and science
      organizer (on the jubilee date)].

PMID- 15462218
TI  - Epiduroscopy--a review.

PMID- 15462219
TI  - Carotenaemia in children is common and benign: most can stay at home.
AB  - We identified children with elevated plasma carotene levels who attended the
      Royal Hospital for Sick Children, Glasgow, between July 1998 and April 2001 and
      carried out a retrospective case record review. Thirty-one children were
      identified (7 boys; 14 girls) with a median age at presentation of 13 months
      (range 7m- 11yrs). Twenty-seven (87%) children had simple diet-related
      carotenaemia and were well. In four cases the hypercarotenaemia reflected
      nutritional problems with associated failure to thrive. In only one case did the
      family doctor recognise the condition before referral. Many who attended hospital
      had laboratory confirmation of the benign diagnosis despite a clear dietary
      origin. Some had repeat laboratory tests to confirm resolution. Diet-related
      carotenaemia appears common in our community. The condition appears poorly
      recognised within primary care and hospital investigations may be over
      enthusiastic.

PMID- 15462220
TI  - The impact of specialist management of jaundiced alcoholic liver disease
      patients.
AB  - BACKGROUND: Patients with alcoholic liver disease (ALD) presenting with jaundice
      have advanced chronic ALD and/or acute alcoholic hepatitis. Their prognosis is
      poor. These patients may be managed by General Medical physicians (GM) or by
      Gastroenterologists (GE). AIM: This study aimed to retrospectively assess the
      differences in management and outcome of jaundiced ALD between GM and GE.
      PATIENTS AND METHODS: Patients with a serum bilirubin greater than 80 mmol/l on
      admission and a history of alcohol excess until within three weeks of admission
      were identified retrospectively. In particular the use of corticosteroids (CS),
      nutritional support (N) and the use of broad-spectrum antibiotics (A/b) were
      noted. RESULTS: 97 patients were identified, 62 managed by GE. Differences were
      apparent between GE and GM managed patients with respect to CS (p = 0.017), N (p
      < 0.001) and A/b (p < 0.001). The overall mortality was 27.8%, 34.0%, and 37.1%
      at 28, 56, and 84 days respectively. Mortality for patients with a Discriminant
      Function approximately 32 was greater in GM managed patients compared with GE at
      28 (p = 0.006), 56 (p = 0.013), and 84 days (p = 0.036). CONCLUSION: Differences
      exist between the management of jaundiced ALD between GM and GE. Such differences
      may translate into improved outcomes.

PMID- 15462221
TI  - The Scotland Leukaemia Registry audit of incidence, diagnosis and clinical
      management of new patients with chronic myeloid leukaemia in 1999 and 2000.
AB  - The management of CML has recently become increasingly complex. The Scotland
      Leukaemia Registry (SLR) sent questionnaires to all 26 Scottish haematology
      units, of which 18 (69%) responded. From January 1999 to December 2000, 64 new
      cases of CML were identified by the audit (incidence 0.64/100,00/yr), of which 46
      were registered with the SLR. At diagnosis, all 18 units combined bone marrow
      examination with cytogenetics/FISH, but only 13 performed RT-PCR. Of four units
      that calculated the Hasford Score, only two used it to inform clinical decisions.
      52% of patients entered clinical trials, 57% involving imatinib mesylate (IM). Of
      the 23 patients who were tissue typed, suitable donors were found for 18, 11
      sibling, and 7 unrelated, representing 28% of the total patient population. Only
      13/64 patients (20%) did not have a BMT donor identified or enter a clinical
      trial. Although 38% of units would consider reduced intensity allografting in
      patients > 60 years, no centres currently routinely tissue-type such patients.
      For first line therapy 56% of patients received hydroxyurea +/- interferon. Of
      the newer agents, 83% of units believed imatinib mesylate should be reserved for
      clinical trials, 83% would consider using oral ara-C and 89% pegylated
      interferon.

PMID- 15462222
TI  - Outcome of halo immobilisation of 104 cases of cervical spine injury.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVES: To present and discuss the
      outcome of halo jacket immobilisation of cervical spine injuries. SETTING:
      National Spinal Injuries Unit in a Scottish University teaching Hospital.
      METHODS: Retrospective review of case-notes and radiographs of all patients
      treated with halo jacket both as primary means of immobilisation or as adjunct to
      surgical stabilisation between 1992-1999 and followed up at a weekly halo clinic.
      RESULTS: Out of a total one hundred and four patients with cervical spine injury,
      eighty-six were treated with Halo jacket as primary means of cervical
      immobilisation. Halo was used as adjunct to surgical stabilisation for the rest.
      There were nine cases of true failure. This is a failure rate of 10% for primary
      halo immobilisation. Of the nine patients who had failure of bony healing, four
      had fibrous healing, three had surgery to stabilise spine, two were subsequently
      lost to follow-up. The highest incidence of recurrence of subluxation occurred in
      patients with fracture/subluxation with a healing rate of 85%. Patients with
      ankylosing spondylitis did well. Odontoid fractures had 18% failure rate. The
      commonest complication was loss of reduction, followed by pin-site infection.
      CONCLUSION: Halo is an effective non-surgical treatment for the injured cervical
      spine at both upper and lower levels.

PMID- 15462223
TI  - How should we train physicians for remote and rural practice? What the present
      incumbents say.
AB  - OBJECTIVE: To obtain the views of the current remote and rural consultant
      physicians with regards to their opinion on components of an ideal training
      programme for an aspirant remote and rural physician. DESIGN: A questionnaire was
      designed to elicit information in three main areas: experience and training prior
      to appointment, current pattern of service provision and opinions on components
      of an ideal training programme for remote and rural physicians. SETTING: Five
      Scottish rural hospitals in Shetland, Wick, Stornoway, Fort William and Oban.
      SUBJECTS: Thirteen consultant physicians based in the five rural hospitals
      chosen. RESULTS: The response rate to the questionnaire was 85%. All had previous
      experience in acute general medicine, and most in one of a variety of
      subspecialties. Each physician had developed interests and skills in other
      branches of medicine following appointment in order to meet local service needs.
      Most felt that there was a need for expansion of consultant numbers in the
      future, 45% citing the European Working Time Directive as the major reason. There
      was an encouraging degree of commonality between the current consultants as to
      what they felt should be included in a training programme for remote and rural
      physicians. CONCLUSION: There are challenges in meeting training needs for
      consultant physicians intending to work in a remote setting. Development of
      broader-based training than offered by most current dual training programmes is
      essential. Only imaginative approaches to training will produce physicians who
      are fit for purpose.

PMID- 15462224
TI  - Erectile dysfunction: a significant health need in patients with coronary heart
      disease.
AB  - BACKGROUND AND AIMS: Erectile dysfunction (ED) is a common condition, which
      negatively affects quality of life, and shares similar risk factors with Coronary
      Heart Disease (CHD). Studies from the pre - sildenafil era confirm a higher risk
      of ED in patients with cardiovascular disease. The high profile and success of
      sildenafil therapy has made it easier for some men to discuss erectile
      difficulties with healthcare professionals. Our aim therefore was to estimate the
      prevalence of ED in our cardiac rehabilitation patients . METHODS AND RESULTS: We
      surveyed 150 random male cardiac rehabilitation patients using the International
      Index of Erectile Function (IIEF) questionnaire. 61% of all respondents had
      erectile difficulties, rising to 75% in the over 55 age group. 48% of respondents
      indicated their wish to discuss erectile problems with the healthcare team.
      CONCLUSION: ED and CHD commonly co-exist. A large proportion of our respondents
      wished further discussion of erectile insufficiency. We recommend that cardiac
      rehabilitation programmes should adopt a proactive approach to detection and
      treatment of ED.

PMID- 15462225
TI  - Constipation and soiling--outcome of treatment at one year.
AB  - AIM: To assess the outcome at one year of a cohort of patients referred to
      outpatient clinics with soiling. METHOD: Retrospective case note audit of 34
      children referred to hospital outpatients over a four month period with soiling
      stated as the main problem in the referral letter. RESULTS: After one year, 29%
      of the 34 children studied were discharged to patient satisfaction, 38% defaulted
      from follow up, 24% were still attending outpatient clinics and 9% had been
      referred back to source. Coexisting pathologies, in particular enuresis and
      family stress, were found in several of the children. At the time of referral,
      44% of new patients and 89% of re-referrals bad symptoms present for longer than
      12 months. Only 18% of the children were receiving treatment at the time referral
      was made. CONCLUSION: Constipation is often undiagnosed until the problem is well
      established with soiling present, which makes treatment a long and often
      difficult process. It is necessary to consider the wider social and family issues
      when managing a child with constipation and soiling. Hospital based general
      medical and surgical outpatient clinics may not be the ideal setting in which to
      deal with these problems.

PMID- 15462226
TI  - Epidemiology of multiple sclerosis in Glasgow.
AB  - STUDY OBJECTIVE: The objectives of the study were to establish the prevalence and
      incidence of multiple sclerosis in Glasgow and to assess the epidemiological
      importance of deprivation and ethnicity. DESIGN: The study was a descriptive
      cross-sectional study. Multiple sources of ascertainment were used to identify
      cases. SETTING AND PATIENTS: The study was carried out in the population of three
      Local Health Care Cooperatives (LHCCs) in the area of Greater Glasgow NHS Board.
      The total population was approximately 169,000. MAIN RESULTS: In total, 245
      patients with multiple sclerosis were identified. The mean age of patients was
      49.8 years, the female to male ratio was 3.2:1, and the mean duration of disease
      was 16 years. The overall prevalence was 14.5 per 10,000, and the overall
      incidence 5.7 per 100,000 per year. Both the prevalence and incidence of multiple
      sclerosis were higher in the more affluent population. The crude prevalence in
      the Asian population was 6.3 per 20,000. CONCLUSIONS: The epidemiology of
      multiple sclerosis in Glasgow was similar, in most respects, to the epidemiology
      described in other parts of the U.K. There was evidence for the importance of
      deprivation as a determinant of both incidence and prevalence of disease. The
      reasons for the higher incidence and prevalence of multiple sclerosis in less
      deprived populations are not clear.

PMID- 15462227
TI  - Emergency presentation of an elderly female patient with profound hypoglycaemia.
AB  - We present the case of an elderly non-diabetic female who was admitted to
      hospital as an emergency due to loss of consciousness. Her clinical presentation
      was consistent with hypoglycaemia due to a massive insulin overdose. However, the
      patient refuted the possibility of insulin administration, and the circumstances
      were reported to the police for investigation. This case demonstrates the
      clinical and biochemical characteristics of insulin overdose. Furthermore, it
      serves to illustrate the sequence of events that may be created when foul play is
      suspected, and the factors related to patient confidentiality that require
      consideration by the responsible physician.

PMID- 15462228
TI  - Case of a late presentation of cor triatriatum in a woman born with an
      imperforate anus.
AB  - Cor triatriatum and imperforate anus are rare. We describe, for the first time,
      the coexistence of these conditions in a 43 year old woman.

PMID- 15462229
TI  - Fatal calcific uraemic arteriolopathy (CUA): a case report and review of the
      literature.
AB  - Calciphylaxis, now better known as Calcific uraemic arteriolopathy (CUA), is an
      uncommon condition characterised by small vessel calcification and occlusion with
      resultant painful violaceous skin lesions that typically ulcerate to form non
      healing gangrenous ulcers. The syndrome is usually found in patients with renal
      failure. In this report we describe a 61 year old lady who developed lower limb
      ulceration secondary to calciphylaxis and discuss the current treatment options
      for this serious condition.

PMID- 15462230
TI  - Hans Christian Andersen's visit to James Young Simpson.
AB  - Preparations are currently underway in Denmark for the celebration in 2005 of the
      200th anniversary of the birth of that country's illustrious son Hans Christian
      Andersen. The renowned author of fairy tales had a passion for travel and
      recorded in his diary and in the several editions of his autobiography his
      encounters with the dignitaries and celebrities of his day. On this anniversary
      we recall the little-known occasion on which Hans Andersen was entertained to
      dinner and to a demonstration of the effects of inhalation of ether at the home
      of James Y. Simpson.

PMID- 15462231
TI  - Personality traits in relation to alcohol dependence and abuse and psychiatric
      comorbidity among women: a population-based study.
AB  - This study investigates relationships between personality traits, alcohol
      dependence and abuse (ADA), and psychiatric comorbidity in a general population
      sample of women. The study is based on data from a previous study by this group
      titled "Women and Alcohol in Goteborg." Altogether, 316 women were interviewed.
      Personality traits were assessed with the Karolinska Scales of Personality (KSP)
      and lifetime psychiatric diagnoses given according to The Diagnostic and
      Statistical Manual of Mental Disorders, Third Revised Edition (DSM-III-R).
      Compared with the reference group, women with a lifetime diagnoses of ADA were
      more anxious, tense, socially conformist, impulsive, and irritable. They were
      also more easily fatigued, and less satisfied with their present life situation
      and childhood experiences. This was more marked among women with current ADA than
      in women with resolved ADA. Women with other psychiatric diagnoses resembled
      women with ADA, according to the KSP. The results indicate that personality
      interacts with all diagnoses included, and possibly influences the development of
      ADA.

PMID- 15462232
TI  - Life stress events and alcohol misuse: distinguishing contributing stress events
      from consequential stress events.
AB  - This study examined the relationship between life stress events and level of
      alcohol misuse using two stress indices. The first index consisted of stress
      events that are not likely to be caused by alcohol misuse (i.e., alcohol
      uncontaminated stress events). The second stress index consisted of items that
      were judged as being likely consequences of alcohol misuse (i.e., alcohol
      contaminated stress events). Results based on a questionnaire study of 378
      undergraduates in 2000 showed that level of alcohol misuse was much more strongly
      related to alcohol contaminated life stress events than alcohol uncontaminated
      life events. Comparative analysis of the coefficients of determination indicated
      the effect size of the association to alcohol contaminated life stress events was
      240% larger than the corresponding effect size for the association to alcohol
      uncontaminated life events. Results suggest that studies, which are tests of the
      tension reduction hypothesis, should employ greater methodological rigor to
      ensure measures of life stress events are not inadvertently assessing the
      consequences of alcohol misuse. The results highlight the need to distinguish
      between stressful life events that contribute to alcohol misuse and stressful
      life events that are consequential to alcohol misuse.

PMID- 15462233
TI  - Psychological correlates of comorbid gambling in psychiatric outpatients: a pilot
      study.
AB  - This study compared psychiatric outpatients with and without lifetime gambling
      problems on clinical disorder and personality disorder scales, and the
      relationship of these scales with involvement in gambling. One hundred and sixty
      two adults (females = 112) in an urban, outpatient psychiatric setting completed
      the South Oaks Gambling Screen (SOGS; Lesieur, H. R., Blume, S. B. (1987). The
      south oaks gambling screen (SOGS): a new instrument for the identification of
      pathological gamblers. Am. J. Psychiatry 144(9):1184-1188) and the Millon
      Clinical Multiaxial Inventory-II (MCMI-II; Millon, T. (1987). Manual for the MCMI
      II: 2nd Edition. Minneapolis, MN: National Computer Systems, Inc.) after their
      initial psychiatric evaluation in 1999. Avoidant and compulsive personality
      features were significantly related to gambling problem status. The Self
      Defeating and Dysthymic Disorder scales were positively associated with gambling
      involvement. The Alcohol Dependence scale was predictive of gambling involvement
      for males only. Findings are somewhat consistent with the literature examining
      comorbidity in pathological gamblers seeking treatment, although no association
      was found with antisocial personality disorder.

PMID- 15462234
TI  - Characteristics of heroin addicts entering methadone maintenance treatment:
      quality of life and gender.
AB  - STUDY OBJECTIVE: To provide information on MMP patient's characteristics,
      particularly those related with Health Related Quality of Life (HRQoL) and
      gender. DESIGN: Cross-sectional study. Data were collected on socio-demographic,
      toxicological variables, HIV risk behaviors, and HRQoL through the Nottingham
      Health Profile (NHP). PATIENTS AND SETTING: Over a 30-month period (1996--1999)
      Barcelona's Municipal Drug Care Centres recruited 586 patients. MAIN RESULTS:
      Mean age of patients was 31 years, 70% were males and 25% were HIV-infected.
      Rates of unemployment, criminal records and low educational level were high. Most
      poly-drug users used cocaine. NHP mean score was related with poly-drug use,
      educational level and HIV status. Consistent condom use was related with HIV
      status. Females' route of administration was less likely to be injection, even
      though they were more frequently HIV-positive and manifested contemporary poorer
      general health. CONCLUSIONS: Patients QoL was poor. Nowadays harm reduction
      health strategies would need to face cocaine use, and sexual risk behaviors
      mainly among females and sexual partners.

PMID- 15462235
TI  - Motivational interviewing and treatment retention among drug user patients: a
      pilot study.
AB  - The effect of motivational interviewing (MI) on retention in the context of an
      outpatient and drug-free heroin-program is evaluated. Heroin users (N=40) seeking
      treatment were randomly assigned to MI or to control conditions. Results
      indicated that participants who received MI significantly increased retention
      rates in comparison to the control group six months after the commencement of the
      treatment program (50%, as against 20%). These results suggest that MI could be a
      useful instrument for improving retention rates in drug-free treatment programs
      during the initial phases of treatment, when the majority of "drop-outs" from
      these programs are recorded.

PMID- 15462236
TI  - In-home continuing care services for substance use affected families.
AB  - The role of in-home work with substance use affected family members has great
      potential for addressing family and personal issues that are often not well
      addressed by continuing care interventions that involve limited contact with the
      family and the impact alcohol and other drug "abuse" has on the family
      environment. This article reviews the importance of involving the family in the
      recovery process and offers comparative advantages of an in-home visitation
      approach for assisting the substance user with maintaining substance use
      avoidance, reintegrating with the family, and addressing unresolved family issues
      affecting children and spousal relationships.

PMID- 15462237
TI  - Simultaneous drinking and gambling: a risk factor for pathological gambling.
AB  - The aim of the current study was to determine the effect of simultaneous drinking
      and gambling on negative consequences from gambling. Data was analyzed from a
      national telephone survey of 2631 US residents aged 18 or older. Males were more
      likely than females to drink while gambling. Simultaneous drinking and gambling
      was more closely associated with video keno, pull tabs, dice (not in a casino)
      and casino gambling than with other types of gambling. Those who drank while
      gambling were more likely to be problem gamblers, even when holding constant
      frequency of gambling, size of the average win or loss, and average alcohol
      consumption. Those gamblers who are drinkers, but did not drink while gambling,
      had a prevalence of problem gambling of close to zero. They had a lower
      prevalence of problem gambling than gamblers who didn't drink alcohol at all in
      the past year, and a much lower prevalence than those who drank while gambling.
      These results were interpreted to mean that simultaneous drinking and gambling is
      an indicator of a more reckless gambler. The results did not support the theory
      that gambling while under the influence of alcohol causes more risky gambling
      behavior.

PMID- 15462238
TI  - Pleasure: from onthogenesis to addiction.
AB  - Among the various models proposed for understanding the dynamics of addiction to
      psychoactive substances, no single one succeeds in explaining how the three
      dimensions--biological, psychological, and social--interact. The physio
      pathological models proposed so far suffer from too reductive a vision of the
      notion of pleasure to hope to supply this explanation. Studies in the
      neurosciences and genetics indicate that cerebral function, and hence pleasure
      itself, is determined less by our genes than by the continuous interaction that
      occurs between every organism and its environment, including other individuals.
      These indications make it possible to propose an integrated model capable of
      answering the main questions posed by all types of addiction.

PMID- 15462239
TI  - Preventing suicide in young schizophrenics who are substance "abusers".

PMID- 15462240
TI  - HRSA's failures, drug overcharges lead to overhaul of 340B agency.

PMID- 15462243
TI  - New drugs and dosage forms.

PMID- 15462242
TI  - Conference sheds light on supply chain challenges.

PMID- 15462244
TI  - Recent changes to FDA-approved labeling.

PMID- 15462245
TI  - Urgent care pharmacotherapy clinic.

PMID- 15462246
TI  - Hospital-based emergency contraception.

PMID- 15462247
TI  - Visual compatibility of bivalirudin with selected drugs.

PMID- 15462248
TI  - Harvey A. K. Whitney Lecture. The discontent of professionalism: a call in the
      night.

PMID- 15462249
TI  - Leadership with conscience, compassion, and commitment.

PMID- 15462250
TI  - Long-acting risperidone injection.
AB  - PURPOSE: The pharmacology, pharmaceutics, clinical efficacy, adverse effects,
      cost, and dosage and administration of long-acting risperidone injection are
      reviewed. SUMMARY: Risperidone is the first atypical antipsychotic available in a
      long-acting injectable formulation. After a single injection, significant plasma
      levels of the drug are achieved at week 3 and sustained through week 6, subsiding
      by weeks 7-8. Steady state is achieved after four injections. Peak levels are
      less than those seen with comparable doses of oral risperidone. A 12-week double
      blind placebo-controlled study and a one-year open-label study demonstrated the
      efficacy, safety, and tolerability of long-acting risperidone injection in
      patients with schizophrenia and schizoaffective disorder. Those who were
      considered stable on their previous medication showed continued clinical
      improvement and an increase in health-related quality of life during a year of
      treatment with long-acting risperidone injection. In the 12-week study,
      risperidone was well tolerated, with adverse-effect rates similar to those seen
      with placebo. Weight gain with long-acting risperidone injection is similar to
      that found with oral treatment. Extrapyramidal symptom ratings have shown
      improvement from baseline following administration of this agent. Individuals
      with schizophrenia who previously received oral risperidone therapy have shown a
      reduction in prolactin levels after a switch to the long-acting formulation.
      CONCLUSION: With its unique tolerability and efficacy, long-acting risperidone
      injection has the potential to extend the benefits of assured medication delivery
      and improved long-term outcomes to more patients with schizophrenia.

PMID- 15462251
TI  - Current approaches to the management of osteoporosis in men.
AB  - PURPOSE: The epidemiology, pathophysiology, diagnosis, and management of
      osteoporosis in men are reviewed. SUMMARY: Men with osteoporosis account for
      approximately one fifth of all patients with osteoporosis, and their morbidity
      and mortality rates from this disease are higher than in other patients.
      Guidelines specifically addressing the management of osteoporosis in men are not
      available. Lifestyle modifications, including smoking cessation, limited alcohol
      consumption, routine exercise, and fall prevention strategies, are beneficial to
      maintain bone health. Appropriate calcium and vitamin D intakes are critical
      components of any osteoporosis management strategy. Drug therapy should be
      initiated in all men at high risk for fracture. Alendronate is indicated for the
      treatment of osteoporosis. It is considered first-line therapy because of its
      efficacy and safety profiles. Teriparatide is indicated for the management of
      osteoporosis in high-risk men, but the drug's cost, complex administration
      schedule, and potential risks have caused it to be restricted to a second-line
      therapy. Other options reserved for select patients include calcitonin and
      testosterone. Further studies are needed to better understand the distinctive
      features and management strategies for men with osteoporosis. CONCLUSION: While
      the rate of osteoporosis in men is lower than in women, the consequences are
      possibly more devastating. Evaluation of secondary causes, especially
      hypogonadism, is important, as they can play a significant role in the
      development of osteoporosis in men. All men should be educated to improve
      modifiable risk factors and maintain recommended daily intakes of calcium and
      vitamin D. Bone mineral density should be evaluated in high-risk men using
      central dual energy x-ray absorptiometry, and drug treatment should be considered
      in those with a history of low-trauma fracture or significant bone loss.

PMID- 15462252
TI  - Vancomycin dosing in high flux hemodialysis: a limited-sampling algorithm.
AB  - PURPOSE: The feasibility of using a limited-sampling algorithm for administration
      of vancomycin for treatment of vascular-access-related bacteremia in outpatient
      high flux hemodialysis was investigated. METHODS: The original vancomycin-dosing
      algorithm used at our hemodialysis unit required stat orders for serum vancomycin
      concentrations before each hemodialysis session to determine the dose of
      vancomycin to be administered posthemodialysis. Vancomycin concentration data
      obtained using this original algorithm from January through September 2001 were
      retrospectively analyzed to determine how many vancomycin concentrations measured
      5-20 microg/mL and identify potential clinical predictors of vancomycin removal.
      RESULTS: A total of 409 serum vancomycin concentrations were drawn during the
      study period. Ninety-seven percent of concentrations drawn were within 5-20
      microg/mL. Twenty-eight patients had data evaluable to determine pharmacokinetic
      parameters. Mean +/- S.D. vancomycin removal was 39% +/- 13%. Body weight and
      duration of dialysis alone, blood flow rate, and dialysate flow rate were not
      predictive of vancomycin removal. Based on these data, a revised algorithm with
      limited vancomycin sampling data was initiated in December 2002. Retrospective
      analysis of concentrations obtained and achieved by this algorithm demonstrated a
      70% reduction in the number of vancomycin concentration determinations, with 93%
      of these concentrations within 5-20 microg/mL. The estimated annual cost saving
      to the hemodialysis unit with the revised algorithm was 7552 dollars. CONCLUSION:
      A vancomycin-dosing algorithm using limited concentration monitoring for
      hemodialysis patients achieved comparable vancomycin concentrations to those
      found with more frequent monitoring and resulted in significant cost savings.

PMID- 15462253
TI  - Pharmacist-facilitated enrollment in medication assistance programs in a private
      ambulatory care clinic.
AB  - PURPOSE: Efforts to reduce patients' out-of-pocket expenses for prescription
      drugs by incorporating pharmaceutical manufacturer assistance programs (PMAPs)
      into a private ambulatory care facility's pharmaceutical services are described.
      SUMMARY: From March 2001 through March 2002, the clinic's pharmacist
      prospectively evaluated patients for PMAP enrollment. The pharmacist completed
      the pharmaceutical manufacturer's application forms for patients identified as
      candidates for PMAP assistance and helped them obtain documentation. Some
      companies sent medications directly to patients, and others sent them to the
      clinic, where they were stored until the patients picked them up. The patients
      informed the pharmacist when refills were needed, which allowed the pharmacist to
      review patient records, verify compliance, and ensure proper follow-up. Forty
      four patients were enrolled in 22 PMAPs during the year. The mean +/- S.D. annual
      household income for all patients was 15,631 dollars +/- 7,845 dollars. A total
      of 115 medication orders were processed for the patients. The mean +/- S.D.
      number of medications per patient obtained through PMAPs was 2.5 +/- 1.8, and the
      mean +/- S.D. number of refills was 1.8 +/- 1.0. The total cost of the
      medications was 48,143 dollars. The pharmacist needed an average of 15-20 minutes
      to perform the initial patient interview, 10-15 minutes to complete each initial
      application, and 5-15 minutes to complete a renewal application. Total pharmacist
      time needed to process each medication order was estimated at about one hour per
      year. CONCLUSION: A pharmacist in a private ambulatory care facility helped
      patients enroll in PMAPs and reduced the patients' expenses for prescription
      drugs.

PMID- 15462254
TI  - Proposal to improve MedWatch: decentralized, regional surveillance of adverse
      drug reactions.

PMID- 15462255
TI  - Immunocytochemical analysis of AE1/AE3, CK 14, Ki-67 and p53 expression in
      benign, premalignant and malignant oral tissue to establish putative markers for
      progression of oral carcinoma.
AB  - Squamous cell carcinoma (SCC) is the most common form of oral malignancy and is
      often preceded by premalignant lesions, some of which are more likely to progress
      to carcinoma than others. In this study, a panel of monoclonal antibodies
      (AE1/AE3, cytokeratin [CK] 14, Ki-67 and p53) is applied to 10 cases of human
      oral tissue in each of six categories to establish staining patterns indicative
      of which lesions are more likely to progress to malignancy. The six tissue
      categories are normal tissue; abnormal benign lesions; mild, moderate and severe
      dysplasia; and SCC. A statistical analysis of Ki-67 and p53 immunoexpression is
      performed. The results showed that AE1/AE3 and CK 14 expression was reduced as a
      late event in oral carcinogenesis, particularly in poorly differentiated SCC.
      Expression of Ki-67 and p53 proved to be a weak but statistically significant
      predictor of malignant progression in oral tissue.

PMID- 15462256
TI  - In vitro cytotoxicity testing of a nanocrystalline silver dressing (Acticoat) on
      cultured keratinocytes.
AB  - Acticoat is a polyethylene mesh coated with nanocrystalline silver. It has been
      used widely as a dressing for chronic wounds, acute partial-thickness burn wounds
      and donor sites. In this study, the in vitro cytotoxicity of Acticoat on cultured
      keratinocytes is tested. Human keratinocytes are cultivated on a pliable
      hyaluronate-derived membrane (Laserskin) using dermal fibroblasts as the feeder
      layer. When the cultured Laserskin (CLS) is subconfluent it is covered by
      Acticoat, which is exposed to water (Group 1), phosphate-buffered saline (Group
      2) or culture medium (Group 3). The control group is not exposed to the Acticoat.
      After 30 minutes incubation at 37 degrees C, the inhibitory effect of the
      nanocrystalline silver on keratinocyte growth is measured by an MTT assay.
      Compared with the control, the relative viability of the CLS dropped to 0%, 0%
      and 9.3%, respectively. Thus, Acticoat is cytotoxic to cultured keratinocytes and
      should not be applied as a topical dressing on cultured skin grafts.

PMID- 15462258
TI  - Evaluation of the continuing professional development scheme of the Institute of
      Biomedical Science.
AB  - As part of a review of the Continuing Professional Development (CPD) scheme of
      the Institute of Biomedical Science (IBMS), 10 years after it started, a survey
      was conducted. A questionnaire was distributed to all Institute members in July
      2002. By the end of September, replies had been received from 777 biomedical
      scientists, representing a range of ages, grades and disciplines, and working for
      a variety of employers throughout the UK and overseas. The majority of
      respondents (n = 687) were current participants in the IBMS CPD scheme, but 74
      replies were received from members who had not previously taken part. Half the
      respondents who were both scheme participants and Associate members of the IBMS
      and one-third of participating Fellows had yet to claim a diploma. The results
      showed that the IBMS CPD scheme was well respected among biomedical scientists,
      but many reported some difficulties in obtaining study leave and financial
      support to attend credited activities. Although respondents felt that an
      individual's own time should not be spent on CPD, activities that are performed
      when off duty (e.g., journal-based learning) are popular, especially among staff
      in younger age groups and among junior biomedical scientist grades. Respondents
      suggested that the scheme could be improved by provision of more resources at
      departmental level to allow regular participation for individual biomedical
      scientists. They also recommended inclusion of competency testing within CPD and
      a simplified diploma system. The IBMS scheme has been well received and has the
      potential to evolve into a good scheme to serve the profession's needs into the
      21st century.

PMID- 15462257
TI  - Synthetic organic food colouring agents and their degraded products: effects on
      human and rat cholinesterases.
AB  - Most synthetic coloured additives are carcinogenic; teratogenic and cause
      allergic reactions. In this study, the effects of synthetic azo dyes (sunset
      yellow FCF and carmoisine), as well as their degraded products (sulphanilic acid
      and naphthionic acid), on both true and pseudo-cholinesterases (ChEs) are
      studied. The results indicate that the synthetic azo dyes and their degraded
      products inhibit both human true and pseudo-ChE activities in vitro. The
      concentration of coloured additive that cause 50% inhibition (IC50) and enzyme
      inhibitor dissociation constant (Ki) show that sunset yellow FCF produces greater
      inhibition of both true and pseudo-ChEs than does carmoisine and sulphanilic
      acid, while naphthionic acid produces greater inhibition of pseudo-ChE only. Ki
      indicates that the affinity of sulphanilic acid for both true and pseudo-ChEs is
      higher than the other three inhibitors. Inhibition of both true and pseudo-ChEs
      by sunset yellow FCF is of mixed (competitive and non-competitive) type, but
      carmoisine and sulphanilic acid are non-competitive. Naphthionic acid produces a
      competitive inhibition kinetic with plasma ChE only. This inhibition is abolished
      by dialysis, indicating that their effects are reversible. The effects of sunset
      yellow FCF, carmoisine, sulphanilic acid and naphthionic acid on rat true and
      pseudo-ChEs are investigated. The data clearly show that there is a significant
      decrease in enzyme activity. Sulphanilic acid and sunset yellow FCF are the most
      potent in vivo inhibitors of true ChE and pseudo-ChE, respectively.

PMID- 15462259
TI  - Effect of aestivation of Biomphalaria pfeifferi on the survival and infectivity
      of Schistosoma mansoni cercariae.
AB  - Schistosoma mansoni cercariae from post-aestivated Biomphalaria pfeifferi remain
      motile for 20 hours after release. Thereafter, their activity decreases with age.
      The difference in mortality rate of cercariae from aestivated and non-aestivated
      B. pfeifferi studied here proved to be statistically significant (P < 0.05)
      within the first 10 hours of the experimental period. Results of the percentage
      recovery of worms from different mouse organs infected with cercariae from
      aestivated and non-aestivated snails varied. The two main organs infected were
      the liver and intestine. In conclusion, the penetration, migration and maturation
      of cercariae into adult worms were not affected by the aestivation of B.
      pfeifferi.

PMID- 15462260
TI  - An oligonucleotide microarray for the detection of vaccinia virus.
AB  - Vaccinia virus is a member of the orthopoxvirus group, to which also belongs
      variola virus, one of the most hazardous pathogens known to man. To establish a
      model system to detect orthopoxviruses, a vaccinia oligonucleotide microarray is
      designed, produced and tested. Vaccinia virus is used to test the prepared
      microarrays. The virus DNA samples in different propagation phases are extracted
      and hybridised with the oligonucleotide microarray. The results showed that the
      oligonucleotide microarray can detect vaccinia virus with high specificity and
      sensitivity.

PMID- 15462261
TI  - Reduction in neutrophil elastase concentration by recombinant alphal-antitrypsin
      (recAAT) does not alter bacterial loading in the sputum of cystic fibrosis
      patients.

PMID- 15462262
TI  - Molecular (PCR) detection of Pseudomonas spp. other than P. aeruginosa directly
      from the sputum of adults and children with cystic fibrosis.

PMID- 15462263
TI  - Life-threatening post-partum hypercalcaemia.

PMID- 15462264
TI  - A case of 'crouching' triglyceride and 'hidden' cholesterol.

PMID- 15462265
TI  - Molecular typing of Dientamoeba fragilis.

PMID- 15462266
TI  - Improved efficiency of a hepatitis C virus antibody testing algorithm in blood
      donors from Saudi Arabia.

PMID- 15462267
TI  - Factor V Leiden: association with venous thromboembolism in pregnancy and
      screening issues.
AB  - Disturbances of the natural balance between procoagulant and anticoagulant
      mechanisms can result in bleeding or thrombotic tendencies. Factor V, on
      activation by thrombin to factor Va, forms an essential component of the
      prothrombinase complex, in which it demonstrates its cofactor activity for factor
      Xa. Down-regulation of factor Va by activated protein C (APC) occurs through
      cleavage of specific peptide bonds in the heavy chain of the molecule. Factor V
      Leiden (FV Leiden) is a mutation of factor V that renders factor Va resistant to
      APC, due to loss of one of these cleavage sites. This mutation predisposes the
      patient to thrombosis. Prevalence of FV Leiden varies; however, heterozygosity
      for the FV Leiden mutation is recognised as the most common heritable
      thrombophilic defect in Caucasian populations. The association this inherited
      thrombophilia has with venous thromboembolism (VTE) is well established.
      Pregnancy is notably an acquired hypercoagulable state, due in part to
      physiological changes that occur in the coagulation system. This seems to have
      potential for interaction with FV Leiden to cause adverse experiences. A role has
      been suggested for FV Leiden in VTE events during pregnancy. At present only
      selected women are screened for FV Leiden. Pregnant women with a history of VTE
      or with a family history of the mutation are investigated. Whether or not the
      introduction of a routine screening plan for this mutation is justified remains a
      matter for debate.

PMID- 15462268
TI  - Don't forget about hydrogen sulphide.

PMID- 15462269
TI  - Antiglobulin tests.

PMID- 15462270
TI  - Zambian dilemma, American solution.

PMID- 15462271
TI  - A medical school dropout.

PMID- 15462272
TI  - Brown Medical School: class of 2004.

PMID- 15462273
TI  - The meta-curriculum in medical education.

PMID- 15462274
TI  - The history of urethral catheterization.

PMID- 15462275
TI  - Rhode Island Hospital Morbidity and Mortality Conference, a case of persistent
      fever and odynophagia.

PMID- 15462276
TI  - Recognition and treatment of depression in long-term care facilities.

PMID- 15462277
TI  - Trends and patterns in hospital inpatient utilization, 2000-2002.

PMID- 15462278
TI  - Evidence of effective screening mammography among Rhode Island women: trends by
      socioeconomic status.

PMID- 15462279
TI  - Sexual boundary violations in the physician-patient relationship.
AB  - Sexual misconduct with a patient violates the physician-patient relationship.
      Such behavior maybe an isolated event in the professional life of a physician,
      but more frequently is part of a pattern of predatory behavior. Such behavior on
      the part of any physician adversely affects all physicians and the public
      welfare.

PMID- 15462280
TI  - A seniority in words.

PMID- 15462281
TI  - Effect of an oral therapeutic HIV-1 vaccine on AIDS patients with CD4 count above
      250 cells/mm3.
AB  - A simple delivery route, e.g. oral, would greatly facilitate the acceptance of an
      AIDS vaccine by a large target population. We developed a vaccine that took
      advantage of inherent properties of mucosal immunity in response to oral antigen
      challenge, namely the V-1 Immunitor vaccine (V1), which is a polyvalent oral
      Human immunodeficiency virus 1 (HIV-1) vaccine. The vaccine, currently
      manufactured in Thailand, contains pooled, inactivated viral antigens. In order
      to compare this vaccine with HIV-1 therapeutic vaccines reported earlier we
      analyzed retrospectively 13 HIV-1-positive patients that had the baseline CD4 T
      cell counts greater than 250 cells/mm3 (range 270-605 cells/mm3). The patients
      self-administered one 850 mg vaccine tablet at breakfast and dinnertime for an
      average of 32 weeks (median 26 weeks). The treatment was well tolerated without
      any toxic effect. Twelve of thirteen patients (92%) and 9 of 13 patients (69%)
      experienced an elevation in CD4 and CD8 cells. The mean increase in absolute CD4
      and CD8 cell counts across this group was 98 (22%; P = 0.02) and 324 (26%; P =
      0.05) cells/mm3, respectively. Viral plasma load was measured by PCR in six
      patients. The observed viremia reduction was within 1 log unit. Subjective
      parameters, i.e., appetite, energy, and sense of well-being were reported by
      patients as being markedly improved, reflected in a mean body weight gain of 2.75
      kg (P = 0.0008). Oral administration of HIV-1 immunogens provides compelling
      clinical response, especially when patients are treated earlier.

PMID- 15462282
TI  - Molecular characterization of an Infectious bursal disease virus isolate from
      Iran.
AB  - The segment A of an Infectious bursal disease virus (IBDV) isolate from Iran was
      amplified by reverse transcription-polymerase chain reaction (RT-PCR), sequenced
      and compared with published sequences of 26 IBDV isolates from other parts of the
      world. The Iranian isolate showed 8 unique amino acid differences. In addition, 9
      common amino acid differences, namely 3 in VP2, (222 Ala, 256 lIe and 294 lIe), 3
      in VP4 (685 Asn/Ser, 715 Ser and 751 Asp), 2 in VP3 (990 Val and 1005 Ala), and 1
      in VP5 (49 Arg) were found. Phylogenetic analysis indicated that the Iranian
      isolate is closely related to highly virulent (hv) IBDV isolates from Asian
      countries. Nevertheless, it may share a common origin with hv isolates from other
      parts of the world.

PMID- 15462283
TI  - Genetic diversity of chicken anemia virus following cell culture passaging in MSB
      1 cells.
AB  - It has been shown that a chicken anemia virus (CAV) isolates which had undergone
      60 passages in MSB-1 cells (SMSC-1/P60, 3-1/P60) acquired 33-66 nucleotide
      substitutions at the coding region resulting in 13-16 amino acid changes as
      compared to the CAV isolates passaged only 5 times in MSB-1 cells (SMSC-1 and 3
      1) (Chowdhury et al., Arch. Virol. 148, 2437-2448, 2003). In this study we found
      that a low CAV (BL-5) and a high CAV passage (BL-5/P90) differed by only 15
      nucleotide substitutions resulting in 11 amino acid changes. Phylogenetic
      analysis based on VP1 also revealed that both isolates were close to each other
      but not to other CAV isolates from Malaysia, namely SMSC-1 and 3-1.

PMID- 15462284
TI  - Pathogenetical characterization of isolate MHV-60 of mouse herpesvirus strain 68.
AB  - Infection of mice with mouse herpesvirus strain 68 (MHV-68) is an excellent small
      animal model of gammaherpesvirus pathogenesis in a natural host. We carried out
      comparative studies on MHV-60, another isolate of MHV-68. The acute infection of
      BALB/c mice inoculated intranasally (i.n.) with MHV-60 as well as its impact on
      tumor development were investigated. During the acute phase of infection the
      lungs were the main tissues infected. Our results show that MHV-60 has similar
      pathological features like other 4 isolates so far examined, namely MHV-72, MHV
      78, MHV-Sumava inclusive of MHV-68. Nevertheless, MHV-60 differed from other
      isolates in following features: (i) the acute phase of infection was established
      very soon and lasted 10 days post infection (p.i.) in contrast to 14-28 days p.i.
      in the abovementioned isolates with a peak on days 3-5 p.i. The virus could also
      be recovered from the spleen, thymus and kidneys but not in other investigated
      organs. A lymphoproliferative response was associated with splenomegaly. At this
      time an increase in the number of leukocytes and appearance of atypical
      leukocytes in peripheral blood were observed. (ii) the infection was localized in
      the lungs and spleen, while in other isolates it was detected in a much broader
      scale of organs, and (iii) the acute phase of infection was accompanied by a
      massive splenomegaly, which was characteristic for the chronic phase of
      infection. Despite the fact that after clearance of the acute infection the virus
      was hardly detected, the tumor formation was later observed in 22% of infected
      mice as compared to 5% in control non-infected mice.

PMID- 15462285
TI  - Expression of herpes simplex virus 1 glycoprotein D in prokaryotic and eukaryotic
      cells.
AB  - Recombinant plasmids encoding either the full-length glycoprotein D (FLgD) or
      truncated gDs were constructed. The recombinant plasmids were expressed in
      Escherichia coli and BHK-21 cells. The strongest expression was obtained with the
      recombinant plasmid encoding a truncated gD which corresponded to the gD
      ectodomain. The cells transformed with this plasmid showed good exponential
      growth ensuring satisfactory yields of the expressed polypeptide in the form of
      the fusion protein. The fusion protein was biotinylated and efficiently purified.
      The shortest truncated gD, which contained the main continuous antigenic locus
      VII binding neutralization antibody and additional continuous antibody binding
      epitopes, still reacted with specific antibody as proven by immunoblot analysis.
      In addition, a shuttle vector for expression of FLgD in mammalian cells was
      constructed. This vector-transfected BHK-21 cells expressed gD for 40 days during
      9 consecutive passages. The expression of gD began on day 2 and culminated at day
      9 post transfection (p.t.).

PMID- 15462286
TI  - The role of hemagglutinins in the midgut extracts of two lines of Aedes aegypti
      in their susceptibility to Dengue-2 virus.
AB  - Hemagglutinin activity (HA) was studied in the midgut extracts from highly (h)
      and lowly susceptible strains of Aedes aegypti mosquitoes to Dengue-2 virus (DEN
      2). HA in the midgut extracts from these two isofemale strains of mosquitoes was
      high in as compared to (h) mosquitoes. HA was found to be higher with chicken red
      blood cells (RBCs) than with rabbit and human RBCs of O group. Larval midgut
      extracts showed higher activity than those from adult female mosquitoes. Exposure
      of midgut extracts to 100 degrees C for 10 mins destroyed the activity. The
      activity was observed between pH 6 and pH 10. HA in midgut extracts was also
      studied using twenty different carbohydrates; five of them showed an inhibition
      of HA. The inhibitory carbohydrates, when incorporated into DEN-2-infected
      bloodmeal, showed a reduction in the susceptibility of mosquitoes to the virus as
      compared to the control ones fed on the virus alone. Similarly, when these
      carbohydrates were incorporated in the DEN-2-infected inoculum, the inoculated
      mosquitoes showed a reduction in the susceptibility to the virus. HA in the virus
      infected midgut extracts was higher than that in the uninfected controls. These
      results suggest that the presence of HA in the midgut may be one of the factors
      that affect the susceptibility of Ae. aegypti mosquitoes to DEN-2.

PMID- 15462287
TI  - Genetic stability of the attachment glycoprotein of human respiratory syncytial
      viruses during serial passages in cell cultures.
AB  - Thirteen isolates of human respiratory syncytial viruses (HRSV) of groups A and B
      were isolated in HEp-2 cells from nasopharyngeal aspirates (NPA) from the
      children with acute respiratory infections. Three isolates of HRSV of group A
      were propagated in HEp-2 cells in 20 serial passages. Nucleotide sequences of the
      products obtained by RT-PCR from the glycoprotein (G) hypervariable region of the
      original virus isolates in NPA and those after one or several passages were
      compared. All the isolates analyzed showed no changes during passaging in HEp-2
      cells.

PMID- 15462288
TI  - Interaction between genomes of infectious bronchitis and Newcastle disease
      viruses studied by reverse transcription-polymerase chain reaction.
AB  - Reverse transcription-polymerase chain reaction (RT-PCR) with specific primers
      for the S1 gene of IBV and for the fusion protein cleavage site of NDV was used
      for detection of Infectious bronchitis virus (IBV, the family Coronaviridae) and
      Newcastle disease virus (NDV) genomes. The sensitivity of IBV and NDV RT-PCR was
      10(3.7) and 10(3.0) EID50, respectively. Although a multiplex RT-PCR could detect
      and differentiate NDV and IBV genomes present in the same sample, there was a
      slight inhibition of the IBV PCR if a high amount of NDV genome was present in
      the sample. To overcome this problem a separate PCR for each virus was used to
      assess the interaction between vaccine IBV and NDV either inoculated singly or
      together into chickens. In the group vaccinated with the Newcastle disease (ND)
      vaccine alone, the viral genome was detected on days 2, 4 and 7 post vaccination
      (p.v.), while in the chickens given the infectious bronchitis (IB) vaccine alone,
      the viral genome was detected only on day 4 p.v. In the group inoculated with
      both vaccine viruses there was a 10(3)-fold reduction in the cDNA dilution factor
      on day 4 p.v. for both IBV and NDV genomes. This demonstrated clearly that when
      both these vaccines are administered there is a transient reduction in the
      replication of both viruses, probably due to their competition for the same
      target epithelial cells in the respiratory tract.

PMID- 15462289
TI  - A pokeweed antiviral protein gene in roots of Phytolacca americana.

PMID- 15462290
TI  - Growth and chemical defense in relation to resource availability: tradeoffs or
      common responses to environmental stress?
AB  - One aspect of plant defense is the production of constitutive secondary compounds
      that confer toxicity on herbivores and pathogens. The purpose of this study was
      to compare patterns of plant tissue toxicity across gradients of irradiance and
      nutrient content. We measured the potential toxicity (1/LC50) of extracts of six
      species of herbaceous Asteraceae grown under controlled conditions of temperature
      (25 degrees C), humidity (80%), photoperiod (16 h/day), in a range of
      concentrations of a modified Hoagland hydroponic solution (full-strength, 1/5
      dilute, 1/10 dilute, and 1/50 dilute) and under two different light intensities
      (250 and 125 micromol/m2/s). The plants grew from seed for 42 days post
      germination, and randomly chosen plants were harvested each 7 days. We did a
      general measure of potential phytochemical toxicity using an alcohol extraction
      of secondary compounds followed by brine shrimp (Artemia sp.) bioassay. Contrary
      to the carbon/nutrient balance hypothesis, tissue toxicity generally increased
      with decreasing irradiance and nutrient levels, so that plants whose growth was
      most restricted had tissues that were most toxic, although there were species
      specific differences in this trend.

PMID- 15462291
TI  - Food resources sustaining the fish fauna in a section of the upper Sao Francisco
      River in Tres Marias, MG, Brazil.
AB  - With the purpose of determining the principal food resources responsible for
      maintaining the fishery yield in a section of the Sao Francisco River, 6 sampling
      of the fish fauna were made downstream from the Tres Marias Dam, from September
      1996 to July 1997. A total of 1,127 individuals of 35 species were captured,
      using gillnets with mesh sizes varying from 3 to 16 cm. The stomach contents of
      33 species were examined in order to determine their diets. Five trophic guilds
      were established, in the following order of importance: ilyophagous, herbivorous,
      piscivorous, terrestrial invertebrates feeders, and aquatic invertebrates
      feeders. The resources sustaining the fish fauna were mainly of allochthonous
      origin. The ichthyonenosis appears to be mainly dependent on the detritus chain.
      The ciliary forest and seasonal flooding pulses are the main suppliers of food
      for the fish fauna.

PMID- 15462292
TI  - Floristic, frequency, and vegetation life-form spectra of a cerrado site.
AB  - We used Raunkiaer's system to classify in life-forms the vascular plants present
      in 12 random 25 m2 quadrats of a cerrado site. The study area is covered by
      cerrado sensu stricto and is located in the Valerio fragment, at about 22 degrees
      13'S and 47 degrees 51'W, 760 m above sea level, in the Itirapina Ecological and
      Experimental Station, Sao Paulo State, southeastern Brazil. The floristic
      spectrum considers the life-form of each species, while in the frequency
      spectrum, each species is weighted by its frequency. The vegetation spectrum does
      not consider the species at all, but only the individuals in each life-form
      class. In the floristic spectrum, the most represented life-forms were the
      phanerophytes and the hemicryptophytes, as in other cerrado sites. This spectrum
      differed significantly from Raunkiaer's normal spectrum, mainly due to under
      representation of therophytes and over-representation of phanerophytes. The
      floristic and frequency spectra were similar, but both differed from the
      vegetation spectrum. We recommend the floristic spectrum when working at larger
      scales and a description of the phytoclimate is wanted. The vegetation spectrum
      is preferable when working at smaller scales and wanting a quantitative
      description of the physiognomy. The frequency spectrum is not recommended at all.

PMID- 15462293
TI  - Steroid metabolism in vitro during final oocyte maturation in white croaker
      Micropogonias furnieri (Pisces: Sciaenidae).
AB  - Final oocyte maturation (FOM) is a process involving a complex set of genetical,
      biochemical, and morphological mechanisms. FOM involves the shift of a post
      vitellogenic follicle to a pre-ovulated oocyte, which is necessary for
      fertilization by spermatozoan to occur. This process is regulated by a maturation
      inducing steroid (MIS) at the follicular level. In other species of scienids fish
      the MIS, a hydroxilated derivatives of progestagen 17, 20beta, 21-trihydroxy-4
      pregnen-3-one (20beta-S), was identified. Although Micropogonias furnieri is the
      second fishery resource of Uruguay, basic knowledge about its endocrine process
      is very scarce. The aim of this work was to investigate what steroids are
      synthesized in vitro by the oocyte follicle of M. furnieri during the maturation
      process. Fragments of ovary (1 g) in three stages: post-vitellogenic (PV),
      maturing (Mtg), and mature (M) were incubated with 1 microg x g(-1) of tritiated
      progesterone (P) at 30, 60, and 180 min. After extraction with ethanol and
      dichloromethane, steroid metabolites were purified by TLC and rpHPLC. Two
      progesterone derivatives with identical chromatographic properties of 20beta-S
      and 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P) were purified. In other
      Teleost fish these steroids are biologically active as MIS. The 17,20beta-P was
      clearly detected in Mtg and M stages and confirmed by enzymatic oxidation with
      enzyme 20beta-HSD. The 20beta-S was strongly detected in all Mtg oocytes. The
      results do not corroborate 20beta-S as a major hormone synthesized in the ovary
      in FOM as occurs in other scienid fish. A differential steroid synthesis in the
      advanced oocyte stages suggests that the 20beta-S is acting as a MIS in M.
      furnieri.

PMID- 15462294
TI  - Macrothrix flabelligera, a newly-recorded Cladocera Macrothricidae in Brazilian
      freshwaters.
AB  - A short characterization of Macrothrix flabelligera Smirnov, 1992 (Cladocera,
      Macrothricidae) is presented, following a recent record of this species in
      Brazil. General aspects and morphological details of the body of parthenogenetic
      and ephippial females, as well as of males, are described and illustrated.

PMID- 15462295
TI  - Comparative biology of two populations of Lutzomyia umbratilis (Diptera:
      Psychodidae) of Central Amazonia, Brazil, under laboratory conditions.
AB  - Lutzomyia umbratilis is the main vector of cutaneous leishmaniasis due to
      Leishmania guyanensis in northern South America. It has been found naturally
      infected with this species of Leishmania only east of the Rio Negro and north of
      the Rio Amazonas. However, populations of this sand fly species are also present
      in areas south of the Amazon river system, which may act as a geographical
      barrier to the Leishmania guyanensis cycle. With the aim of looking for possible
      biological differences between populations of L. umbratilis from each side of
      this river system, their biology in the laboratory was investigated. Progenitors
      collected on tree bases in Manaus and Manacapuru (east and west, respectively, of
      the Rio Negro) were reared in the laboratory. Results from observations of the
      life cycle, fecundity, fertility, and adult longevity at 27 degrees C and 92% RH
      were analyzed by descriptive statistics and z, t, U, and chi2 tests. Although the
      Manaus and Manacapuru colonies showed a longer developmental time than most
      Lutzomyia species reared at similar temperatures, length of time of egg and 4th
      instar larva of the two populations differed significantly (p < 0.01). Females of
      the latter retained significantly (p < 0.001) less mature oocytes, and the
      general productivity (% adults from a known number of eggs) of the colony was
      significantly (p < 0.01) higher than that of the former. These results show that
      the L. umbratilis population of Manaus is more productive, and thus a better
      candidate for future mass-rearing attempts. The two populations differ in their
      life cycle, fecundity, fertility, adult longevity, and emergence. These
      differences may reflect some divergence of intrinsic biological features evolved
      as a result of their geographical isolation by the Rio Negro. It is expected that
      further investigations on morphometry, cuticular hydrocarbon, isoenzyme,
      molecular and chromossomal analyses, infection, and cross-mating experiments with
      these and other allopatric populations of both margins of the Amazon river system
      will help reveal whether or not L. umbratilis has genetically diverged into two
      or more reproductively isolated populations of vectors or non-vectors of
      Leishmania guyanensis.

PMID- 15462296
TI  - Development and reproduction of Podisus distinctus (Heteroptera: Pentatomidae)
      fed on larva of Bombyx mori (Lepidoptera: Bombycidae).
AB  - Biological control has been reducing the use of chemical products against insect
      pests, especially predatory Pentatomidae. Species of this group can present high
      variations in their life cycle as a result of their diet. Thus, the objective of
      this research was to study nymph development and reproduction of Podisus
      distinctus (Stal, 1860) (Heteroptera: Pentatomidae) fed on Bombyx mori L., 1758
      (Lepidoptera: Bombycidae) larvae (T1), compared to those fed on Tenebrio molitor
      L., 1758 (Coleoptera: Tenebrionidae) (T2) and Musca domestica L., 1758 (Diptera:
      Muscidae) larvae (T3) at a temperature of 25 +/- 0.5 degrees C, relative humidity
      of 70 +/- 2%, and photophase of 12 h. Predators fed on B. mori showed duration of
      the nymph phase (18.68 +/- 1.02) similar to those fed on T. molitor (18.32 +/-
      1.49). Pre-oviposition and oviposition periods and number of egg masses, besides
      eggs and nymphs per female, were higher with B. mori (5.83 +/- 2.02; 15.00 +/-
      7.40; 8.42 +/- 1.84; 296.69 +/- 154.75; and 228.55 +/- 141.04, respectively)
      while longevity of males and females of P. distinctus was 25.76 +/- 16.15 and
      35.00 +/- 16.15 days with T. molitor, and 20.57 +/- 13.60 and 23.46 +/- 12.35
      days with B. mori, respectively.

PMID- 15462297
TI  - Behaviour of dispersion indices in pattern detection of a population of angico,
      Anadenanthera peregrina (Leguminosae).
AB  - In this paper we calculate the values of eight pattern detection indices, using
      different quadrat sizes where individuals of angico above 1.5 m were located, in
      order to examine their statistical behaviour with increasing sample size. It was
      concluded that the best index is the standardized Morisita index (Ip) which is
      completely independent of sample size.

PMID- 15462298
TI  - Marking with pigments for identification of flies in experimental populations of
      Megaselia scalaris Loew.
AB  - The insect marking technique of Tadei & Mourao (1976) is until now the only
      experimental method allowing real-age determination of each individual in a
      population and, consequently, determination of age structure in a given
      population. We propose an improvement of this technique, used here to determine
      the population age structure of the geographical strain SR of the Megaselia
      scalaris Loew (Diptera; Phoridae), maintained by serial transfer technique at
      constant temperatures 25 +/- 1.0 degree C and 20 +/- 1.0 degree C. Determining
      the age structure allowed the calculation of the real longevity of the flies and
      the identification of the effect of temperature decisive factors in these are the
      technique of marking insects, because otherwise we would only have an estimate,
      and depending on mistakes there in, the effect of the determinant factor
      (temperature) cannot be detected.

PMID- 15462299
TI  - Age, growth and yield per recruit analysis of the pintado Pseudoplatystoma
      corruscans (Agassiz, 1829) in the Cuiaba River basin, Pantanal Matogrossense,
      Brazil.
AB  - The age and growth of the pintado Pseudoplatystoma corruscans were studied during
      the period from May 1994 to May 1995. The standard length ranged from 52 to 145
      cm and the weight from 1.3 to 41 kg. The biometric relationship between the
      standard length (Ls) and total length (Ltotal) and between the total weight (Wt)
      and the standard length (Ls) were obtained for the species, being respectively:
      Ltotal = 3.296 + 1.069 * Ls and Wt = 0.00624 * Ls(3.134). The condition factor
      calculated monthly suggests the spawning season to be between the months of
      February and March. The age was estimated by counting growth rings present in the
      spines of the pectoral fins, and 10 age classes were detected. The mean distance
      of the last ring until the border of the spine suggests that the period of least
      growth is between July and September (dry period). Von Bertalaffy's equation
      describing the growth of the pintado is: Lt= 183 * [1 - exp - 0.085 * (t +
      3.274)]. Total mortality was Z = 0.24 year(-1) and natural mortality M = 0.20
      year(-1). As the present level of exploitation, F = Z - M = 0.04 year(-1), we
      conclude that the pintado stock was still underexploited in the Pantanal in the
      sampled period.

PMID- 15462300
TI  - Ureotelism is inducible in the neotropical freshwater Hoplias malabaricus
      (Teleostei, Erythrinidae).
AB  - Increased environmental pH decreases ammonia transport through the gills,
      impairing nitrogenous waste. The consequent toxicity is usually drastic to most
      fishes. A few species are able to synthesize urea as a way to detoxify plasma
      ammonia. We studied three teleosts of the family Erythrinidae living in distinct
      environments, and assumed the biochemical behaviors would be different in spite
      of their being closely related species. Adult fish collected in the wild were
      submitted to alkaline water and the urea excretion rate was determined. The
      specific activity of urea cycle enzymes was determined in liver samples of fish
      from neutral waters. The studied species Hoplias lacerdae, Hoplerithrynus
      unitaeniatus, and Hoplias malabaricus are ureogenic. Urea synthesis is not a
      metabolic way to detoxify ammonia in H. lacerdae and Hoplerithrynus unitaeniatus
      exposed to an alkaline environment. The plasma ammonia profile of both species
      showed two distinct biochemical responses. Urea excretion of H. malabaricus was
      high in alkaline water, and the transition to ureotelism is proposed. The
      nitrogen excretion rate of H. malabaricus was among the highest values reported
      and the high urea excretion leads us to include this species as ureotelic in
      alkaline water.

PMID- 15462301
TI  - NADP-dependent isocitrate dehydrogenase of Astyanax scabripinnis (Pisces,
      Characidae) from three altitudes at Grande Stream, Campos do Jordao, SP.
AB  - Electrokinetic, thermic, and kinetic properties of products of NADP-dependent
      isocitrate dehydrogenase (IDHP; EC 1.1.1.42) loci of Astyanax scabripinnis
      (Pisces, Characidae) collected at three different altitudes (700 m, 1,800 m, and
      1,920 m) of Grande Stream at Campos do Jordao, State of Sao Paulo, Brazil, were
      analyzed. Two IDHP bidirectionally divergent loci, a single skeletal muscle, the
      IDHP-A*, and a single liver IDHP-B*, both polymorphic, were detected in the three
      different altitude populations. The variant allele *128 at the IDHP-A* locus, had
      its highest frequency detected in the 1,920 m population (0.494). Among the nine
      variant alleles detected at the IDHP-B* locus (*37, *57, *69, *79, *85, *114,
      *119, *124, and *140), the *37 and 79 were detected only in 1,800 m population.
      Chi-square values showed that only the 700 m population is not in Hardy-Weinberg
      equilibrium for the IDHP-A* locus, while for the IDHP-B* locus, no population is.
      Homogeneity Chi2 test indicated that the populations are significantly different
      in their A and B phenotype frequencies. Wright's FST mean value (0.036 and 0.32,
      IDHP-A* and IDHP-B*, respectively) was 0.178 for the three altitude populations
      which means that 82% of total genetic diversity was found among individuals of
      each one of the populations. Stability at environmental temperatures (16 degrees
      to 21 degrees C), and apparent Km and Vmax values of each A-phenotype skeletal
      muscle crude extract suggest different roles of A-isoforms during the increased
      lipogenesis that occurs in fish at low temperatures.

PMID- 15462302
TI  - Feeding behavior of the cirratulid Cirriformia filigera (Delle Chiaje, 1825)
      (Annelida: Polychaeta).
AB  - Observations of the feeding behavior of Cirriformia filigera (Delle Chiaje, 1825)
      (Annelida: Polychaeta) from the intertidal zone of Sao Francisco and Engenho
      D'agua beaches (Sao Sebastiao, State of Sao Paulo) were made in the laboratory.
      This species, like other cirratulids, is a deposit feeder, feeding mainly on
      sediment surface with the aid of its grooved and ciliated palps, which are used
      to capture food particles. The worm lies just beneath the substrate surface in a
      J-shaped tube. When feeding, it extends up to 4 palps over the sediment surface,
      capturing food particles which pass down the groove of each palp directly to the
      mouth. Only fine sand grains are ingested. The worm frequently extends 4
      branchial filaments into the overlying water for aeration. When it moves with the
      prostomium sideways, it collects and transports sand grains that pass backwards
      along its ventral region until reaching the middle part of its body. Next, the
      parapodia and palps move the sand grains to the dorsal posterior end of the
      animal, covering this area with sand. Some sand grains are also ingested as the
      worm moves.

PMID- 15462303
TI  - Diel vertical migration of copepods in a Brazilian lake: a mechanism for
      decreasing risk of Chaoborus predation?
AB  - A comparison between two studies on diel vertical migration of two cyclopoid
      copepod species, in Lake Monte Alegre, undertaken in 1985/86 and 1999, revealed a
      change in their migratory behavior. In summer, during a period of marked
      stratification with low dissolved oxygen near the bottom, the organisms avoided
      the deepest layers, and migration was nocturnal or undetectable, in both periods.
      On other occasions, with partial or total circulation in the lake, a weak
      twilight migration of copepodites and adults in 1985 was replaced by the reverse
      in 1999. Differences were found among stages, with the weakest or undetectable
      migration being observed for nauplii. The migratory pattern change for
      copepodites and adults might be related with a recent predation pressure increase
      by Chaoborus larvae on copepods, after the virtual disappearance of their main
      cladoceran prey.

PMID- 15462304
TI  - Worldwide patterns in species richness of Falconiformes: analytical null models,
      geometric constraints, and the mid-domain effect.
AB  - Recently, the hypothesis that the geographic distribution of species could be
      influenced by the shape of the domain edges, the so-called Mid-Domain Effect
      (MDE), has been included as one of the five credible hypotheses for explaining
      spatial gradients in species richness, despite all the unsuccessful current
      attempts to prove empirically the validity of MDE. We used data on spatial
      worldwide distributions of Falconiformes to evaluate the validity of MDE
      assumptions, incorporated into two different sorts of null models at a global
      level and separately across five domains/landmasses. Species richness values
      predicted by the null models of the MDE and those values predicted by Net Primary
      Productivity, a surrogate variable expressing the effect of available energy,
      were compared in order to evaluate which hypothesis better predicts the observed
      values. Our tests showed that MDE continues to lack empirical support, regardless
      of its current acceptability, and so, does not deserve to be classified as one
      possible explanation of species richness gradients.

PMID- 15462305
TI  - Functional response of Cosmoclopius nigroannulatus (Hem.: Reduviidae) to
      different densities of Spartocera dentiventris (Hem.: Coreidae) nymphae.
AB  - This study evaluated the functional response of the predator Cosmoclopius
      nigroannulatus on first instar nymphae of Spartocera dentiventris, both species
      associated with Nicotina tabacum. The experiment was carried out in laboratory
      conditions: 27 +/- 1 degree C; 80 +/- 5%, RH; 12 h, photophase. Ten newly emerged
      adults of each sex of C. nigroannulatus were used in each of five densities (5,
      15, 25, 35, and 45 individuals) of S. dentiventris nymphae. The predators were
      observed every 24 h for five days, when the number of dead and/or consumed
      nymphae was recorded. The results showed a positive correlation between the
      number of ingested nymphae and the increase in prey density. Females ingested
      more nymphae than the males. The estimated handling time per prey (Th) was higher
      in males (3.07 h) than in females (1.93 h), with total handling time (Th x Na)
      increased with density. Other components of the functional response, such as
      attack rate (a'), searching time (Ts), and search efficiency (E) showed, in
      neither males nor females, a negative correlation regarding density. The results
      indicated a higher predatory efficiency in the females. The components of the
      functional response fitted significantly the randomic model of the Holling discs
      equation (Na = N [1 - exp[- a'(T - ThNa)]]), evidencing a functional response of
      type II.

PMID- 15462306
TI  - Evaluation of biochemical and serological methods to identify and clustering
      yeast cells of oral Candida species by CHROMagar test, SDS-PAGE and ELISA.
AB  - The purpose of this work was to evaluate biochemical and serological methods to
      characterize and identify Candida species from the oral cavity. The strains used
      were five Candida species previously identified: C. albicans, C. guilliermondii,
      C. parapsilosis, C. krusei, C. tropicalis, and Kluyveromyces marxianus, as a
      negative control. The analyses were conducted through the SDS-PAGE associated
      with statistical analysis using software, chromogenic medium, and CHROMagar
      Candida (CA), as a differential medium for the isolation and presumptive
      identification of clinically important yeasts and an enzyme-linked
      immunoabsorbent assay (ELISA), using antisera produced against antigens from two
      C. albicans strains. This method enabled the screening of the three Candida
      species: C. albicans, C. tropicalis, and C. krusei, with 100% of specificity. The
      ELISA using purified immunoglobulin G showed a high level of cross-reaction
      against protein extracts of Candida species. The SDS-PAGE method allowed the
      clustering of species-specific isolates using the Simple Matching coefficient,
      S(SM) = 1.0. The protein profile analysis by SDS-PAGE increases what is known
      about the taxonomic relationships among oral yeasts. This methodology showed good
      reproducibility and allows collection of useful information for numerical
      analysis on information relevant to clinical application, and epidemiological and
      systematical studies.

PMID- 15462307
TI  - Differentiation and genetic variability in natural populations of Anopheles (N.)
      triannulatus (Neiva & Pinto, 1922) of Brazilian Amazonia.
AB  - Populations of Anopheles triannulatus from Macapa (AP), Aripuana (MT), Ji-Parana
      (RO), and Manaus-Janauari Lake (AM) were studied using 16 enzymatic loci. The
      results of the isozyme analysis showed that the population of Macapa presented
      higher polymorphism (56.3%). The lowest variability was observed in the
      population of Manaus (p = 25.0; Ho = 0.077 +/- 0.046). The results of Wright's F
      statistics showed unbalance due to excess of homozygotes (F(is) > F(st)),
      denoting a certain intrapopulational differentiation. Although the populations
      are genetically very close (D = 0.003-0.052), the dendrogram separates the
      populations in two groups: Macapa separated from that of Manaus, Ji-Parana, and
      Aripuana. This result may suggest a reduction in the genic flow, which possibly
      had some influence in the substructuration of the populations.

PMID- 15462308
TI  - A study of the fish community structure in a tidal creek.
AB  - The fish assemblage in a mangrove tidal creek was studied in monthly collections
      between August 1998 and July 1999 in the quadrature low tide and high tide, using
      a fyke net of 30 m x 1.5 m and meshes of 8 and 10 mm. Simultaneously with the
      biological collections, temperature, salinity, pH, water transparency, and
      current speed data were obtained. The collections resulted in the capture of
      36,873 fish representing 22 families and 52 species. Immature individuals
      abounded (63.8%), and among the adult specimens there was a larger number of
      females. The species Anchoa parva, Harengula clupeola, Genidens genidens, and
      Bairdiella ronchus, contributed to 84.9% of the total capture of fish, however
      the contribution in mass was of 55.2%, indicating a predominance of small
      individuals. A smaller number of fish and species seem to occupy the area in the
      period between August and December, in comparison to the period between February
      and July, when the larger aggregations appear, mainly of the species Anchoa
      parva, Harengula clupeola, Opisthonema oglinum, Genidens genidens, Diapterus
      rhombeus, and Bairdiella ronchus. The environmental factors, pH, water
      transparency, and rainfall seem to have an influence in the structure of the
      observed biological patterns.

PMID- 15462309
TI  - Natural history of the lizard Enyalius brasiliensis (Lesson, 1828) (Leiosauridae)
      from an Atlantic forest of southeastern Brazil.
AB  - Information on the ecology of lizard species from the Brazilian Atlantic Forest
      is scarce and almost nothing is known about the ecology of lizards of the genus
      Enyalius. In this study, we provide information about some aspects of the natural
      history of E. brasiliensis from an area of Atlantic Forest in Ilha Grande, RJ.
      Enyalius brasiliensis (N = 15) feeds mainly on arthropods. The most frequent food
      items were insect larvae, orthopterans, and ants; in terms of volume, larvae and
      termites were the most important food items; ants and termites were the most
      numerous prey categories. Two females were reproductive (one had 10 and the
      other, five vitellogenic follicles); the smallest measured 92.4 mm in SVL. Seven
      lizards were found on forest leaf litter. The other microhabitats used were
      vines, fallen logs, branches, and a crevice on a slope.

PMID- 15462310
TI  - Nest spacing and architecture, and swarming of males of Dinoponera quadriceps
      (Hymenoptera, Formicidae) in a remnant of the Atlantic forest in Northeast
      Brazil.
AB  - Dinoponera quadriceps is a queenless neotropical ponerinae ant. Nest spacing and
      abundance were investigated in a remnant of the Atlantic forest in Northeast
      Brazil. Males were captured with a light trap between August 1994 and July 1996.
      Nest density varied from 15 to 40 ha(-1). An overdispersion of nests suggests
      that the intraspecific competition may be an important factor regulating their
      spatial arrangement. Territory size was correlated with worker population size of
      the colonies. The nests had up to 16 chambers, with variations in their
      architecture closely related to habitat diversification. Populations varied from
      12 to 97 adult workers per nest, with a mean density of 1,618 workers ha(-1) and
      a live biomass of 461 g ha(-1) (n = 13 nests). Males swarm continually throughout
      almost all months of the year, suggesting that production and swarming are more
      influenced by mechanisms that regulate the sexual activity of workers than by
      climatic factors.

PMID- 15462311
TI  - Seasonality of the activity pattern of Callithrix penicillata (Primates,
      Callitrichidae) in the cerrado (scrub savanna vegetation).
AB  - Two wild groups of Callithrix penicillata, the Black Pincelled Marmoset, were
      observed from January to September 1998, in two areas, one an area of dense scrub
      savanna vegetation (cerrado) and the other, a semidecidual woodland (cerradao),
      both within the boundaries of the Ecological Reserve of IBGE (Brazilian Institute
      of Geography and Statistics), in an environmentally protected area, the APA
      (Portuguese abbreviation for "environmental protected area") Gama/Cabeca-de
      Veado, Brasilia, DF. The behavioral data collected during the rainy (January 15
      to April 15) and dry season (June 1 to September 15) were compared. Because of
      the proximity to the Reserve facilities, the group from the dense scrub savanna
      vegetation (CD) was submitted to antropic impacts different from the group in the
      semidecidual woodland (CE), which was using as territory an area that had been
      suffering from man-made fires every two years as part of a long-term experimental
      project on fire impacts. The behavioral data was quantified by instantaneous
      cross-section ("scan sampling") every ten minutes with records of locomotion,
      rest, foraging for insects, use of exudate, and feeding. During the whole year,
      the greatest percentage of time spent by CE and CD was in foraging for insects,
      with 44% and 39%, respectively. It was evident when comparing the data for the
      two seasons that, for both groups, foraging for insects was more intense during
      the dry season, possibly to complement the shortage of food, and locomotion
      increased during the rainy season. The greater the availability and distribution
      of fruit in the areas, the greater the locomotion of the groups to obtain these
      resources. None of the other behavioral patterns, including the use of exudates,
      presented significant differences between the two seasons. Both groups foraged
      more frequently during the dry season and locomoted more during the rainy one.

PMID- 15462312
TI  - [Combination of cholelithiasis and duodenal ulcer: general nature of pathogenetic
      mechanisms].
AB  - Studies have shown that patients with cholelithiasis include a large group of
      people having associated duodenal ulcer as well. Duodenal ulcer also precedes
      cholelithiasis quite often (the ratio being 4:1), which makes it possible to
      consider duodenal ulcer as one of the risk factors for the duodenal ulcer
      development.

PMID- 15462313
TI  - [Clinical and pharmacoeconomic substantiation of the modification of eradication
      therapy regimens for Helicobacter pylori-associated diseases].

PMID- 15462314
TI  - [Microbiocenosis of the bowels in patients with gastroduodenal ulcers].
AB  - Gastroduodenal ulcer is accompanied by the bowels dysbacteriosis irrespective of
      the Helicobacter pylori infection. Any variant of ulcer treatment aggravates the
      bowels dysbacteriosis intensity. Eradication therapy destroys Bifidobacteria
      mostly.

PMID- 15462315
TI  - [Pharmacoeconomic aspects of Helicobacter pylori-associated duodenal ulcer].

PMID- 15462316
TI  - [Assessment of the dental status, acid-base balance in the oral cavity and Ph of
      the gastric medium during the use of the Dirol chewing gum].
AB  - The goal of our research was to study the short-term and long-term effects of the
      Dirol chewing gum on the oral cavity state and acid-forming stomach function in
      patients with hyperchlorhydria. It was revealed that the rational use of this
      chewing gum by patients with increased gastric secretion can normalize the
      gastric acidity. Another result of the use of this chewing gum is the improvement
      of the oral cavity hygienic state and reduced growth of dental caries.

PMID- 15462317
TI  - [Experience of application of Esomeprazole in patients with chronic hepatic
      diseases associated with acid-dependent diseases].
AB  - Esomeprazole is efficient for acid-dependent diseases of the gastrointestinal
      tract in patients with chronic hepatitis and hepatic cirrhosis as it can reduce
      the disease symptoms and cause the epithelization of erosive and ulcerative
      defects of the mucous coat. The terms of the cicatrisation of erosive and
      ulcerative defects of the mucous coat of the esophagus, stomach and duodenum are
      comparable in patients with liver diseases and in the population (without chronic
      hepatic diseases). The simultaneous application of Nexium and modern hepatotropic
      drugs does not cause the development of hepatotoxic reactions.

PMID- 15462318
TI  - [Causes of the growth of complicated gastroduodenal forms of ulcer].

PMID- 15462319
TI  - [Determination of the hereditary and constitutive predisposition to peritoneal
      commissures].
AB  - The determination of the hereditary and constitutive predisposition to peritoneal
      commissures before an abdominal operation and preventive introduction of an
      anticommissural drug into the abdominal cavity after the operation (in case such
      a predisposition is revealed) will make it possible to avoid repeated operations
      caused by commissures. Moreover, economic benefit of the introduction of
      anticommissural drugs and methods for the determination of the constitutive
      predisposition to peritoneal commissures before abdominal operations will make up
      about 20 billion USD for the whole Russia only owing to the reduction of cases of
      peritoneal commissures.

PMID- 15462320
TI  - [A case of the surgery of cholelithiasis complicated with choledocholithiasis and
      formation of a cholecystoduodenal fistula in an elderly female patient].

PMID- 15462321
TI  - [Association between the level of serum pepsinogen I and markers of the
      Helicobacter pylori infection in teenagers].
AB  - The concentration of pepsinogen I as well as antibodies to Helicobacter pylori
      and CagA protein were determined in the blood serum in 84 schoolchildren at the
      age of 14-17 using the immune-enzyme analysis. The level of pepsinogen I did not
      depend on the sex, age, gastroenterological symptoms and ulcer occurrence in
      parents. However, the concentration of pepsinogen was higher in teenagers
      infected with H. pylori (89.6 ug/l) than in non-infected ones (69.4 ug/l, p =
      0.012), this increase taking place mostly due to strains containing CagA.

PMID- 15462322
TI  - [Dynamics of markers of blood inflammation against the background of
      antibacterial therapy in children with mucoviscidosis, with the various regimens
      of intake of pancreatic enzymes].
AB  - The results of the studies show that patients with mucoviscidosis diagnosed for
      the first time who do not receive any adequate replacement pancreatic therapy
      should not be prescribed high doses of pancreatic enzymes along with
      antibacterial therapy when they are hospitalized on account of exacerbation of
      the bronchopulmonary process. Sharply increased lipid absorption can cause an
      aggravation of oxidative stress and impair the patient's state instead of
      improving it. In our opinion, such patients should be prescribed delayed adequate
      pancreatic therapy with immediate introduction of high doses of antioxidants
      (vitamins E, A, C, beta-carotene, etc.). There is no doubt that it is necessary
      to conduct further research into the problem for a greater number of patients.

PMID- 15462323
TI  - [Particular features of application of proton pump inhibitors (Rabeprazole) in
      children with the gastroesophageal reflux disease].

PMID- 15462324
TI  - [Method of proton magnetic resonance spectroscopy of the blood serum in the
      forecasts of the clinical course and diagnostics of suppurative complications in
      patients with pancreatonecrosis and pancreatogenic infiltration].

PMID- 15462325
TI  - [Burrill Crohn (1884-1983)--an outstanding gastroenterologist of the XX Century].

PMID- 15462326
TI  - [Description of the process of disablement of the population in the Republic of
      Uzbekistan].

PMID- 15462327
TI  - [Gastroesophageal disease: state of the problem and issues for discussion].

PMID- 15462328
TI  - Unearthing the subject of mining waste.

PMID- 15462329
TI  - Incorporation of sewage sludge in clay brick and its characterization.
AB  - This study reports the use of sewage sludge generated from sewage treatment plant
      (STP) as raw material in a clay brick-making process. The physico-chemical and
      mineralogical characterization of the sewage sludge and clay were carried out in
      order to identify the major technological constraints and to define the sludge
      pretreatment requirements if necessary. Moreover, the effects on processing
      conditions and/or on changes of typical final characteristics are also evaluated.
      Bricks were produced with sewage sludge additions ranging from 10 to 40% by dry
      weight. The texture and finishing of the surface of sludge-amended clay bricks
      were rather poor. As for the physical and chemical properties, bricks with a
      sludge content of up to 40 wt.% were capable of meeting the relevant technical
      standards. However, bricks with more than 30 wt.% sludge addition are not
      recommended for use since they are brittle and easily broken even when handled
      gently. A tendency for a general degradation of brick properties with sludge
      additions was observed due to its refractory nature. Therefore, sludge bricks of
      this nature are only suitable for use as common bricks, which are normally not
      exposed to view, because of poor surface finishing.

PMID- 15462330
TI  - An alternative method for the treatment of waste produced at a dye and a metal
      plating industry using natural and/or waste materials.
AB  - The aim of this study was to develop cost-effective, appropriate solidification
      technologies for treating hazardous industrial wastes that are currently disposed
      of in ways that may threaten the quality of local groundwater. One major
      objective was to use materials other than cement, and preferably materials that
      are themselves wastes, as the solidification additives, namely using wastes to
      treat wastes or locally available natural material. This research examines the
      cement-based and lime-based stabilization/solidification (S/S) techniques applied
      for waste generated at a metal-plating industry and a dye industry. For the lime
      based S/S process the following binder mixtures were used: cement kiln dust/
      lime, bentonite/lime and gypsum/lime. For the cement-based S/S process three
      binder mixtures were used: cement kiln dust/cement, bentonite/cement and
      gypsum/cement. The leachability of the wastes was evaluated using the toxicity
      characteristic leaching procedure. The applicability and optimum weight ratio of
      the binder mixtures were estimated using the unconfined compressive strength
      test. The optimum ratio mixtures were mixed with waste samples in different
      ratios and cured for 28 days in order to find the S/S products with the highest
      strength and lowest leachability at the same time. The results of this work
      showed that the cement-and lime-based S/S process, using cement kiln dust and
      bentonite as additives can be effectively used in order to treat industrial
      waste.

PMID- 15462331
TI  - Recent trends and current practices for secondary processing of zinc and lead.
      Part I: lead recovery from secondary sources.
AB  - Implementation of stricter environmental laws and economic reasons has forced all
      the metallurgical industries to go for eco-friendly technologies to produce metal
      and other related products. However, generation of wastes is an integral part of
      metallurgical industries. If the wastes/residues are hazardous in nature, they
      generally have to be treated or/and disposed of in safe and designated dumping
      sites. If these wastes/residues are non-hazardous in nature, then they may be
      suitable for use as secondary raw material to recover metals such as lead, copper
      etc., which are in growing demand all over the world. The processing of lead
      secondaries is important because of their relative high metal content, as well as
      the low energy and cost involved in recovering the metal. This paper mainly
      focuses on the current practices and recent trends in the secondary processing of
      lead. Various processes, particularly hydrometallurgical ones, already developed
      or in the development stages, are discussed. Attempts made by various Council of
      Scientific and Industrial Research (CSIR) Laboratories including the National
      Metallurgical Laboratory (NML) and industries such as Binani Zinc to develop eco
      friendly processes for the recovery of lead from secondary raw materials are also
      described.

PMID- 15462332
TI  - Recent trends and current practices for secondary processing of zinc and lead.
      Part II: zinc recovery from secondary sources.
AB  - Almost all metallurgical processes are associated with the generation of wastes
      and residues that may be hazardous or non-hazardous in nature depending upon the
      criteria specified by institutions such as the US Environment Protection Agency,
      etc. Wastes containing heavy and toxic metals such as arsenic, cadmium, chromium,
      nickel, lead, copper, mercury, zinc, etc., that are present beyond permissible
      limits deemed to be treated or disposed of, and non-hazardous wastes can be
      utilized for metal recovery or safe disposal. Zinc is in growing demand all over
      the world. In India, a major amount of zinc is imported and therefore processing
      of zinc secondaries will assist in satisfying the gap between demand and supply
      to some extent. This report mainly focuses on the current practices and recent
      trends on the secondary processing of zinc. Attempts made by various laboratories
      to develop ecofriendly processes for the recovery of zinc from secondary raw
      materials are also described and discussed.

PMID- 15462333
TI  - Effect of sintering temperature on the properties and leaching of incinerator
      bottom ash.
AB  - The fine particle size fraction of municipal solid waste incinerator bottom ash
      is often problematic because reuse applications for this material are limited. In
      these experiments incinerator bottom ash with a particle size of less than 8 mm
      was processed using conventional ceramic production techniques involving wet
      milling, drying, compacting and sintering. The effect of sintering temperature on
      the sintered density, microstructure, acid neutralization capacity (ANC) and the
      release of metal ions as a function of leachate pH are reported. Sintering at
      1080 degrees C produced samples with maximum density. This material contained
      diopside (CaMgSi2O6), clinoenstatite (Mg2Si2O6) and wollastonite (CaSiO3) as the
      major crystalline phases. The acid neutralization capacity of sintered samples is
      significantly lower than milled bottom ash, and further reduces as the sintering
      temperature increases. This is associated with reduced leaching of Ca from
      sintered ash samples under all leachate pH conditions. Heavy metals present in
      the incinerator bottom ash included Cr, Cu, Ni, Zn, Cd and Pb. Sintering under
      optimum conditions reduced the leachable fraction of these metals under
      aggressive acid conditions (leachate pH 3) by factors ranging from 90% for Ni to
      greater than 99% for Cr, Cd, Zn and Pb.

PMID- 15462334
TI  - Characteristics variation of coal combustion residues in an Indian ash pond.
AB  - Coal-fired power plants all over the world are cited as one of the major sources
      that generate huge quantities of coal combustion residues (CCRs) as solid wastes.
      Most frequently CCRs are collected through electrostatic precipitators, mixed
      with bottom ash by hydraulic systems and deposited in ash ponds. The quality of
      the CCRs at different locations in one of the ash ponds in Central India was
      evaluated to understand the variation in characteristics with a view to effective
      utilization. Results revealed that the presence of fine particles (< 50 mocrom)
      increased with increasing distance from the ash slurry inlet zone in the ash
      pond. Wide variations in the bulk density (800-980 kg m(-3)), porosity (45-57%)
      and water-holding capacity (57.5-75.7%) of CCRs were recorded. With increasing
      distance the pH of the CCRs decreased (from 9.0 to 8.2) and electrical
      conductivity increased (from 0.25 to 0.65 dS m(-3)). The presence of almost all
      the heavy metals in CCRs exhibited an increase with distance from the ash slurry
      discharge zone due to the increase in surface area (from 0.1038 to 2.3076 m2 g(
      1)) of CCRs particles. The present paper describes the variation of
      characteristics of CCRs deposited in the ash pond and their potential
      applications.

PMID- 15462335
TI  - Degradation of fats during thermophilic composting of organic waste.
AB  - The degradation of fats during thermophilic composting was investigated by adding
      lard of four different mixing ratios (0, 33.3, 42.9 and 50% on a dry weight
      basis) to dog food used as a model substrate for organic waste. The lard added at
      the mixing ratio of 33.3% did not inhibit the decomposition of organic matter in
      the dog food, with lard itself beginning decomposition after decay of more easily
      decomposable organic compounds of the dog food, 84 h from the start of
      composting. The percentage of lard decomposition reached as high as 29.3% by the
      end of 8 days of composting. By contrast, the decomposition of organic matter in
      the processed dog food was apparently inhibited when the portion of lard was
      greater than 33.3%, especially at the earliest stage of composting. It is
      possible, however, that lard would decompose vigorously once decomposition has
      begun, even when the ratio of lard is as high as 50%. The percentages of lard
      decomposition in composting mixtures with 42.9 and 50% lard were 15.7 and 9.50%,
      respectively, thus the higher the mixing ratio of lard, the lower the percentage
      of lard decomposition. However, it was found that the maximum decomposition rate
      of the lard was similar for all of the ratios tested; that is, approximately 5.0
      x 10(-3) g carbon h(-1).

PMID- 15462336
TI  - Functional relationships of landfill and landraise capacity with design and
      operation parameters.
AB  - Solid waste management presses for effective landfill design and operation. While
      planning and operating a landfill (LF) or a landraise (LR), choices need to be
      made regarding: (1) LF-LR morphology (base shape, side slopes, final cover
      thickness, LR/LF height/depth); (2) cell geometry (height, length, slopes); and
      (3) operation parameters (waste density, working face length, cover thicknesses).
      These parameters affect LF/LR capacity, operation lifespan and construction/
      operation costs. In this paper, relationships are generated between capacity (C,
      space available for waste) and the above parameters. Incorporating real data into
      simulation kgamma A1.38, runs, two types of functions are developed: first, C =
      where A is the LF/LR base area size and kgamma a base shape-dependent
      coefficient; and second, C = alpha(p,gamma,A) + delta(p,gamma,A)Xp for every
      parameter p, where Xp is the value of p and alpha(p,gamma,A) and delta(p,gamma,A)
      are parameter- and base (shape/size)-specific coefficients. Moreover, the
      relationship between LF depth and LR height that balances excavation volume with
      cover material, is identified. Another result is that, for a symmetrical
      combination of LF/LR, with base surface area shape between square and 1:2
      orthogonal, and final density between 500 and 800 kg m(-3), waste quantity placed
      ranges from 1.76A1.38 to 2.55A1.38 tons. The significance of such functions is
      obvious, as they allow the analyst to investigate alternative LF/LR schemes and
      make trade-off analyses.

PMID- 15462337
TI  - Assessing the use of poplar tree systems as a landfill evapotranspiration barrier
      with the SHAW model.
AB  - The use of poplar tree systems (PTS) as evapotranspiration barriers on
      decommissioned landfills is gaining attention as an option for leachate
      management. This study involved field-testing the Simultaneous Heat and Water
      (SHAW) model for its ability to reliably estimate poplar transpiration,
      volumetric soil water content, and soil temperature at a landfill located in
      southern Ontario, Canada. The model was then used to estimate deep drainage and
      to ascertain the influence of a young PTS on the soil water balance of the
      landfill cover. The SHAW model tended to underestimate poplar transpiration [mean
      difference (MD) ranged from 0.33 to 3.55 mm on a daily total basis] and
      overestimate volumetric soil water content by up to 0.10 m3 m(-3). The model
      estimated soil temperature very well, particularly in the upper 1 m of the
      landfill cover (MD ranged from -0.1 to 1.6 x degrees C in this layer). The SHAW
      model simulations showed that deep drainage decreased appreciably with the
      presence of a young PTS largely through increased interception of rainfall, and
      that PTS have a good potential to act as effective evapotranspiration barriers in
      northern temperate climate zones.

PMID- 15462338
TI  - A historical context of municipal solid waste management in the United States.
AB  - Municipal solid waste management (MSWM) in the United States is a system
      comprised of regulatory, administrative, market, technology, and social
      subcomponents, and can only be understood in the context of its historical
      evolution. American cities lacked organized public works for street cleaning,
      refuse collection, water treatment, and human waste removal until the early
      1800s. Recurrent epidemics forced efforts to improve public health and the
      environment. The belief in anticontagionism led to the construction of water
      treatment and sewerage works during the nineteenth century, by sanitary engineers
      working for regional public health authorities. This infrastructure was capital
      intensive and required regional institutions to finance and administer it. By the
      time attention turned to solid waste management in the 1880s, funding was not
      available for a regional infrastructure. Thus, solid waste management was
      established as a local responsibility, centred on nearby municipal dumps. George
      Waring of New York City organized solid waste management around engineering unit
      operations; including street sweeping, refuse collection, transportation,
      resource recovery and disposal. This approach was adopted nationwide, and was
      managed by City Departments of Sanitation. Innovations such as the introduction
      of trucks, motorized street sweepers, incineration, and sanitary landfill were
      developed in the following decades. The Resource Conservation and Recovery Act of
      1976 (RCRA), is the defining legislation for MSWM practice in America today. It
      forced the closure of open dumps nationwide, and required regional planning for
      MSWM. The closure of municipal dumps caused a 'garbage crisis' in the late 1980s
      and early 1990s. Private companies assumed an expanded role in MSWM through
      regional facilities that required the transportation of MSW across state lines.
      These transboundary movements of MSW created the issue of flow control, in which
      the US Supreme Court affirmed the protection of garbage under the Commerce Clause
      of the Constitution. Thus MSWM in America today is largely managed by
      municipalities, and operated by a relatively small number of private companies.
      It consists of a mixture of landfill, incineration, recycling, and composting,
      and is regulated under RCRA, the Clean Air Act and other related federal and
      state laws.

PMID- 15462340
TI  - [Successful staged repair of a symptomatic neonate of tetralogy of Fallot with
      severe absent pulmonary valve syndrome].
AB  - Tetralogy of Fallot with absent pulmonary valve has been classified to a few
      groups. The most severe one is characterized by symptomatic onset immediately
      after birth. The others are no or slightly symptomatic at least during their
      neonatal period. In a severely symptomatic 12-day-old neonate of tetralogy of
      Fallot with absent pulmonary valve who had required intubation immediately after
      birth, tight pulmonary banding and left side modified Blalock-Taussig shunt were
      performed on emergency basis. Consequently, prior massive pulmonary regurgitation
      was decreased significantly. Forty-five days after this first stage operation, he
      weaned from respiratory management. At 1-year-old, radical repair based on
      conotruncal repair, which consisted of patch closure of ventricular septal defect
      preserving the tricuspid septal leaflet function, resection of anterior wall of
      enlarged left pulmonary artery, and right ventricular outflow tract
      reconstruction using autologous tissue and a pericardial patch was performed.
      Bicuspid pulmonary valve, posterior one of procured autologous pulmonary wall and
      anterior one of polytetrafluoroethylene (PTFE) respectively, was created to
      minimize deterioration of the pulmonary insufficiency. Although postoperative
      cardiac function was kept feasible showing his central venous pressure of 7 mmHg
      in the main, postoperative general course was eventful especially regarding the
      respiratory function. The patient was weaned from the prolonged ventilator
      management 5 months after this radical repair eventually. Generally, to diminish
      the massive pulmonary regurgitation in early lifetime period could reduce a
      progressive airway obstruction and minimize pulmonary tissue damage. However,
      even after the total correction in this case, considerable peripheral segmental
      pulmonary obstructive lesions were persistent according to the perfusion lung
      scanning with 99mTc macroaggregated albumin and 99mTechnegas ventilation lung
      scanning studies. This persistent, supposed to be innate, pulmonary obstructive
      lesions might prevent ordinal recovery after cardiac radical repair for this most
      severe subtype of absent pulmonary valve syndrome.

PMID- 15462339
TI  - [Preoperative evaluation for lung resection using right ventricular hemodynamic
      functions by unilateral pulmonary arterial occlusion test].
AB  - We performed a unilateral pulmonary arterial occlusion (UPAO) test for the
      preoperative evaluation of right ventricular functions as a loading test in
      patients undergoing a lung resection without cardiac complications
      preoperatively. We investigated the relationship between changes in right
      ventricular hemodynamic functions and postoperative cardiac complications, namely
      right heart failure or arrhythmia. To evaluate the right ventricular hemodynamic
      function test, we measured the mean pulmonary arterial pressure, cardiac index,
      right ventricular ejection fraction end-diastolic volume, and stroke volume
      before and during the UPAO test using the thermodilution method, and calculated
      the total pulmonary vascular resistance and right ventricular stroke work
      indexes. The incidence of postoperative cardiac complications was not related to
      the changes in the total pulmonary vascular resistance index. However, the
      postoperative cardiac complications were common in patients whose right
      ventricular end-diastolic volume index was increased by more than 20% during the
      UPAO test. These results suggest that the changes in the right ventricular end
      diastolic volume index during the UPAO test can predict postoperative cardiac
      complications in patients undergoing a pulmonary resection.

PMID- 15462341
TI  - [Long survival with chronic ventricular fibrillation under support of uni-left
      ventricular assist system].
AB  - Few minutes of suspended malignant ventricular arrhythmia may be permitted for
      the patient with left ventricular assist system (LVAS). However, longer and
      continuous ventricular arrhythmia, especially ventricular fibrillation (Vf), may
      induce the low output of LVAS, which leads circulatory collapse immediately. Our
      presenting case is a female dilated cardiomyopathy patient who has been supported
      with LVAS. Four months after the LVAS installation, her electrocardiogram has
      changed to Vf without any symptoms. Her ventricular function has never recovered,
      even ventricular tachycardia. She has been a candidate of heart transplantation
      for more than 19 months with this rare hemodynamic condition (LVAS+Vf), like the
      Fontan circulation. Her performance status is limited due to deceasing of the
      LVAS flow, which caused by the change of her position: 2.5-2.9 l/min (lie down)
      to 2.0 l/min (rise). Her peak VO2/W is 6.9 ml/min/kg measured by the cardio
      pulmonary exercise test. However, she has developed her general status by doing
      rehabilitation program and is able to walk for more than 100-150 meters.

PMID- 15462342
TI  - [Liposarcoma originating in the neck and the mediastinum after removal of
      mediastinal lipoma].
AB  - A 47-year-old man, who had undergone removal of an upper mediastinal lipoma 9
      years previously, was referred to our hospital for swelling of the right neck and
      wheezing. The chest X-ray showed enlargement of the upper mediastinum. Contrast
      enhanced chest computed tomography and magnetic resonance imaging demonstrated a
      tumor with fatty density extended from the upper mediastinim to the right side of
      the neck. Two-stage tumor resection was carried out. On gross pathological
      examination the tumor was soft and fatty. Microscopic examination revealed well
      differentiated liposarcoma. Postoperative radiation therapy (50 Gy) was carried
      out. The patient remains free of disease 3 years after radiation therapy.

PMID- 15462343
TI  - [Surgical treatment of pulmonary metastases from colon and rectal cancer].
AB  - We retrospectively studied the surgical treatment for pulmonary metastases from
      colon and rectal cancer. A total of 24 patients (9 males and 15 females; mean age
      61 years) underwent 29 thoracotomies for metastatic colon carcinoma, while 22
      patients (16 males and 6 females; mean age 63 years) underwent 29 thoracotomies
      for metastatic rectal cancer. The median interval between the primary procedure
      and lung resection for metastases was 26 months in the patients with colon
      carcinoma and 32 months in the patients with rectal cancer. In the patients with
      colon carcinoma, 16 underwent wedge resection or segmentectomy (including 4 video
      assisted procedures) and 13 (54%) underwent lobectomy or pneumonectomy. In the
      patients with rectal cancer, 15 underwent wedge or segmentectomy (including 1
      video-assisted procedure), 13 (59%) underwent lobectomy or pneumonectomy, and 1
      underwent exploratory thoracotomy. All procedures except exploratory thoracotomy
      were curative operations. There was no mortality. Overall 5-year survival was 56%
      (n=46). Five-year survival was 65% for patients with colon metastases (n=24) and
      45% for patients with rectal metastases (n=22), and there was no significant
      difference. Recurrent sites were 4 lungs (36%), 4 livers (36%), 1 bone, 1 uterus,
      and 1 peritoneum in patients with colon carcimoma, and 10 lungs (43%), 5 brains
      (22%), 3 livers (13%), 1 bone, and 1 vagina in patients with rectal cancer.
      Pulmonary resection for metastases from colon carcinoma may have better prognosis
      than that from rectal cancer. However, further investigation may be required to
      obtain convincing conclusions.

PMID- 15462344
TI  - [Operation on acute type A aortic dissection using transapical aortic
      cannulation].
AB  - We experienced a case of operation for acute type A aortic dissection using
      transapical aortic cannulation (TAC). A 62-year-old male with chest and back pain
      admitted to our hospital. The chest computed tomography (CT) showed the
      dissection of total aorta. Hemiarch repair (circulatory arrest time: 64 min, pump
      time: 152 min) was performed by cardiopulmonary bypass (CPB) established with
      bicaval cannulation and TAC in this case. The reason why we use TAC is that
      retrograde perfusion by femoral artery has a high-risk of malperfusion and
      cerebral embolism because of atheromatous change in aorta, and the use of the
      axillary artery can be troublesome because of the vessel's small diameter. We
      considered that in cases of acute aortic dissection, TAC is much safer and
      simpler than femoral or axillary cannulation.

PMID- 15462345
TI  - [Thoracic surgical approach for traumatic diaphragmatic hernia].
AB  - Four patients with traumatic diaphragmatic hernias are reported and are discussed
      from the view point of surgical approach for the repair of diaphragm. All hernias
      were caused by car accidents and the diagnoses were made by routine radiography,
      computed tomography (CT) and magnetic resonance imaging (MRI) examinations. All
      patients were diagnosed clinically and radiologically. There was no associated
      intraabdominal trauma and the surgical approach was through the chest in all
      cases. All but 1 of the patients survived. Abdominal approach at surgery has been
      considered preferable because associated injuries to intra-abdominal organs have
      frequently been encountered in the United States. The outcomes in our series
      indicate that the surgical approach should be based on the clinical and
      radiographic findings in each indicated patient.

PMID- 15462346
TI  - [Observation of the right atrial wall suture line after tricuspid valve supra
      annular implantation].
AB  - Strength of the right atrial wall suture line after tricuspid valve supra-annular
      implantation (TVSI) is controversial. We observed the right atrial supra-annular
      position of a 63-year-old male during his third mitral operation who underwent
      mitral valve replacement (MVR) and TVSI 15 years ago. Eight years later, he
      received the second MVR and removal of the bioprosthetic valve from the tricuspid
      position due to primary tissue failures. The annular size of the tricuspid valve
      had decreased enough to be fixed by tricuspid annuloplasty (TAP) and re-TVSI was
      not needed at that time. In this operation, 7 years following bioprosthetic valve
      removal, the circularly bulging atrial wall still remained and seemed to have
      enough strength for holding the prosthetic valve. This finding may support the
      conclusion that the right atrial wall has enouth strength for holding a
      prosthetic valve in position.

PMID- 15462347
TI  - [Chest wall epithelioid sarcoma].
AB  - Two relatively rare cases of epithelioid sarcoma located in the chest wall are
      reported herein. The first was a tumor, 3.8 x 5.5 x 2.4 cm in size, originating
      in the left erector spinae muscle of a man 64 years of age. He experienced local
      recurrence 3 times even after wide resections, and he died of systemic metastasis
      22 months after the initial surgery. The second was a tumor, 2.2 x 2.0 x 1.5 cm
      in size, originating in the left seventh intercostal muscle of a woman 24 years
      of age. A metastatic tumor occurred in the same muscle, and wide resection
      including the seventh and eighth intercostal muscles was performed. There has
      been no recurrence for 1.5 years since surgery. Metastasis of chest wall
      epithelioid sarcoma in the muscle in which the primary lesion resides should be
      considered, even if the primary lesion is small.

PMID- 15462348
TI  - [Case of systolic anterior motion of mitral valve after mitral valve repair].
AB  - A 56-year-old woman was underwent mitral valve repair for prolapse of the
      posterior mitral leaflet. Intraoperative transesophageal echocardiography (TEE)
      showed systolic anterior motion (SAM) of the mitral valve at the weaning from
      cardiopulmonary bypass (CPB). Sliding technique was easily performed at the
      second pump run. Intraoperative TEE demonstrated no SAM or residual mitral
      regurgitation after the second pump run.

PMID- 15462349
TI  - [Infective endocarditis caused by methicillin resistant Staphylococcus aureus
      following corticosteroid pulse therapy; report of a case].
AB  - A 51-year-old man, with a history of corticosteroid pulse therapy 3 weeks
      previously, developed infective endocarditis of the mitral valve due to
      methicillin resistant Staphylococcus aureus, and underwent mitral valve
      replacement. Since the second postoperative day, clinical course was seriously
      complicated because of recurrent abdominal pain corresponding with commencement
      of oral intake, unremitting spike fever, and renal and hepatic dysfunction.
      Various examinations except angiography failed to demonstrate the etiology. Two
      months later, the patient developed panperitonitis due to perforation of ischemic
      ulcer of the cecum and underwent ileo-cecal resection. After this operation, he
      convalesced very quickly. Ischemia is one of the main causes of abdominal
      complication following cardiac surgery. Angiography should be positively
      considered in cases like the present one.

PMID- 15462350
TI  - [Valvuloplasty for mitral regurgitation immediately following Kawasaki disease
      without abnormal coronary arteries lesion; report of a case].
AB  - It is not uncommon that valve disease is complicated with Kawasaki disease (KD).
      However, it is rare to show normal coronary arteries simultaneously. We
      experienced a case of valvuloplasty towards the mitral regurgitation (MR)
      followed immediately after KD showing normal coronary arteries. A 3 year-old
      female, with a diagnosis of KD at 4 months after birth, was referred to our
      hospital 5 months after birth. The echocardiography detected a moderate MR. The
      preoperative catheterization at 2.5 years old showed grade III MR, enlargement of
      left atrium and left ventricle, pulmonary capillary wedge pressure (PCWP) = 12
      mmHg, left ventricular ejection fraction (LVEF) = 675, and normal coronary
      arteries. Pulmonary hypertention was not revealed. The operative findings showed
      mitral valve prolapse due to the elongation of the chordae of the anterior
      leaflet. She underwent artificial chordal reconstruction using expanded
      polytetrafluoroethylene sutures and mitral annuloplasty by Kay-Reed method. The
      postoperative course was uneventful, and she was discharged on postoperative day
      19.

PMID- 15462351
TI  - [Total arch replacement with reconstruction of non-coronary sinus for acute type
      A aortic dissection after previous coronary artery bypass grafting; report of a
      case].
AB  - A 73-year-old man, who underwent coronary artery bypass grafting (CABG) 2 years
      previously, had suffered from acute type A aortic dissection with concomitant
      mild to moderate aortic regurgitation. A median resternotomy was performed.
      Arterial and venous cannulae were inserted into the femoral artery and vein to
      institute a cardiopulmonary bypass. The intimal tear was existed just above the
      sino-tubular junction. As the non-coronary sinus was involved in the dissection
      severely, it was resected in a scallop-shaped configuration. The aortic graft was
      tailored accordingly and anastomosis was performed in a curviliner fashion
      following the edge of scallop and the horizontally between the right and left
      coronary sinuses. Next, total arch replacement was performed using an aortic arch
      branched graft. Postoperative course was uneventful. Aortography revealed no
      aortic regurgitation and good patency of bypass graft.

PMID- 15462352
TI  - [Bentall operation for a 90-year-old man with root aneurysm; report of a case].
AB  - Open heart surgery in nonagenarians is not common. We reported a successful
      Bentall operation in a 90-year-old man with aortic root aneurysm and aortic
      regurgitation. He has lived healthfully and independently without a big problem.
      He was referred to our hospital for acute heart failure. The aortic root enlarged
      as a diameter of 60 mm and moderate aortic regurgitation were recognized by
      echocardiography and aortogram. We excised the aneurysm, implanted a composite
      graft, directly attached the coronary arteries to the aortic graft (Carrel patch
      technique), and made the distal anastomosis to the divided aorta. Postoperative
      course was uneventful. To our knowledge, this is the first successful case of
      Bentall operation for nonagenarians in Japan. If selective criteria identifying
      risks and benefits for individual patients is applied, the nonagenarian can
      safely undergo cardiac surgery.

PMID- 15462353
TI  - [Lung cancer with an extrapericardial single trunk as the left pulmonary vein;
      report of a case].
AB  - A left lower lobectomy was successfully performed in a lung cancer patient with
      anatomical variation in which the left superior and inferior pulmonary veins were
      connected to the left atrium after forming an extrapericardial single trunk. This
      variation is surgically important because ligation and division of the left
      inferior pulmonary vein may result in blockage of upper lobe vein drainage at the
      time of a left lower lobectomy. The ligation of the pulmonary vein leads to
      severe lung edema, which may cause infection, respiratory distress, or
      postoperative complications that could be life-threatening. Surgeons must always
      pay attention to this variation when performing a left lower lobectomy.

PMID- 15462354
TI  - [Thoracoscopic repair of diaphragmatic thinning for pleuroperitoneal
      communication; report of a case].
AB  - A 53-year-old man presented with massive right hydrothorax just after
      introduction of continuous ambulatory peritoneal dialysis (CAPD). Because the
      glucose concentration of pleural fluid was markedly high compared with that of
      serum, we diagnosed pleuroperitoneal communication. Thoracoscopic surgery was
      performed and thinning of the diaphragm was found. We sutured the diaphragm to
      repair the thin portion and performed pleurodesis with 50% glucose solution. He
      restarted CAPD 1 month post-operatively and continued at home without pleural
      effusion. Eight months post-operatively, he experienced dyspnea again and chest X
      ray showed right hydrothorax. Although the cause of recurrent hydrothorax is
      unknown, it may be that not only surgical repair but also more intense
      pleurodesis is needed.

PMID- 15462355
TI  - [Removal of a steel bar after Nuss procedure for pectus excavatum; report of a
      case].
AB  - Recently, an increasing number of patients have been treated with the Nuss
      procedure for pectus excavatum. One of the merits is that this surgical procedure
      is less invasive and leads to good cosmetic results compared with the former
      traditional procedures such as sternal turn over. We have repaired 60 cases of
      pectus excavatum using the Nuss procedure at our institute since July 1999. We
      have experienced the removal of a steel bar, which was the first case of Nuss
      procedure at our institute.

PMID- 15462356
TI  - [Castleman's disease in the interlobar fissure resected by video-assisted
      thoracoscopic surgery; report of a case].
AB  - An abnormal shadow was detected on the chest X-ray of a 33-year-old man in a
      medical check-up. Chest computed tomography (CT) showed a 2 x 2 x 3 cm tumor
      which was enhanced, round, homogeneous, and adjacent to the pulmonary artery in
      the right interlobar fissure. Video-assisted thoracoscopic surgery was performed
      in August 2002 for diagnosis and treatment. The tumor was surgically removed and
      grossly round, elastic and hard. The histopathological diagnosis was hyaline
      vascular type of Castleman's disease. Postoperative course was uneventful, and
      the patient was discharged on the third postoperative day. Interlobar Castleman's
      disease successfully resected by video-assisted thoracoscopic surgery is rare.

PMID- 15462357
TI  - [Tension hemopneumothorax complicated by severe hepatic and renal disorder;
      report of a case].
AB  - A 46-year-old man was admitted to our hospital because of dyspnea and chest pain.
      We diagnosed tension hemopneumothorax and chest tube drainage was performed. A
      large volume of bloody pleural fluid (1,200 ml) was removed, but severe liver and
      renal dysfunction were then recognized. He was treated conservatively because
      there was no more bleeding. Despite administration of methylprednisolone, re
      expansion pulmonary edema occurred after 6 hours of drainage, but this was also
      treated conservatively. After 3 days, his pneumothorax recurrenced. It was
      successfully managed by video-assisted thoracoscopic surgery (VATS).

PMID- 15462358
TI  - [Recent problem in neurosurgical society].

PMID- 15462359
TI  - [Preoperative embolization of metastatic spinal tumors].
AB  - The authors reviewed their clinical experience with preoperative embolization of
      metastatic spinal tumors. Between October 2000 and September 2003, 20 patients
      (13 men and 7 women; average age 68.3 years, range 44-82 years) underwent 24
      spinal operations for 22 spinal metastatic tumors. Nineteen spinal operations
      (79%) were planned preoperative embolization with polyvinyl alcohol particles. In
      3 cases, there was no tumor stain. Fifty percent of the C4-T2 lesions and 76% of
      the T3-L3 lesions were embolized preoperatively. The level of lesions determined
      which embolization procedure should be used. With C7-T2 or sacral lesions,
      feeding arteries were superselectively catheterized, then particles were injected
      via a microcatheter. With T3-L3 lesions, selective catheterization of the
      corresponding segmental arteries was performed. Particles were injected via 4 or
      5Fr catheters. No complications were encountered during embolization. Embolizing
      from the origin of the segmental arteries is effective for reducing
      intraoperative blood loss because feeding vessels in the anterior part of the
      spinal body are able to be embolized. Preoperative embolization is not a very
      complicated procedure and careful catheterization can avoid complications. Based
      on tumor histology, size of the spinal body, depth of the operative field and
      operative approach, preoperative embolization can be performed with positive
      results.

PMID- 15462360
TI  - [Better understanding of microcatheters in neuroendovascular surgery: product
      properties with steam shaping].
AB  - Microcatheters for neuroendovascular procedure especially for embolization of
      aneurysms are essential tools. Each catheter has it's own property for use.
      However there is very little literature about the character and mechanism of
      microcatheters. With steam shaping, they are often deformed and shortened. We
      herein present technical problems associated with the shaping of microcatheters.
      We have to understand the potential risk of complications related to
      microcatheters.

PMID- 15462361
TI  - [Micro-tourniquet method: a substitute or supporting technique for aneurysm
      clipping].
AB  - The micro-tourniquet method is designed as a substitute and/or supporting
      technique for obliterating aneurysms that are difficult to operate on using the
      conventional clipping technique. This method is useful for squeezing the aneurysm
      neck and making a detour around the neck to spare the branching vessels. These
      micro-tourniquet instruments are a ligature with both ends attached to a ligature
      guide, a guide holder, a silastic sheath, and a hemostatic clip or a small
      aneurysm clip set. The ligature is a 20cm long GORE-TEX suture CV-3, and is
      attached on both ends to a ligature guide. These ligature guides are made of 7mm
      wire, and are malleable enough to be bent intentionally during surgery. However,
      they are also rigid enough to be used as a micro dissector. The silastic sheath
      is made of a 20G infusion needle, and is cut to a length of 2cm. After branching
      vessels and perforators are dissected and spared with the aid of the ligature
      guide, the ligature is passed around the aneurysm neck, both ends of the ligature
      are passed through the sheath, the aneurysm neck is squeezed, and a clip is
      applied as a stopper on the ligatures adjacent to the distal end of the sheath.
      By gently displacing the distal end of the sheath, a conventional aneurysm clip
      is applied on the aneurysm neck just distal or proximal to the ligature on the
      neck. Then, the ligature is removed. Two demonstrable cases are presented and the
      usefulness of the micro-tourniquet method is discussed.

PMID- 15462362
TI  - [Dissecting vertebral aneurysm with subarachnoid hemorrhage after ischemic onset
      on the same day: a case report].
AB  - We report a case of a dissecting vertebral aneurysm with subarachnoid hemorrhage
      (SAH) after ischemic onset on the same day. A 48-year-old man had abrupt vertigo
      and nausea. CT & MRI on admission showed no abnormality, but he complained of
      left hemiparesis after admission. Twelve hours after the ischemic onset he
      suddenly complained of severe headache and his consciousness deteriorated. The
      follow-up CT showed diffuse SAH. Cerebral angiography showed occlusion of the
      right vertebral artery at the origin of the posterior inferior cerebellar artery
      (PICA) and segmental stenosis of the left vertebral artery at the portion distal
      to the vertebral PICA junction. We treated the patient conservatively. Four days
      later, he suddenly fell into a coma, but CT showed no bleeding. Because of this
      we suspected brain stem ischemia due to deterioration of vertebral dissection.
      The patient died 8 hours after the ischemic reattack. We report difficulty of
      treatment of a dissecting vertebral aneurysm with simultaneous ischemia and
      subarachnoid hemorrhage.

PMID- 15462363
TI  - [Currarino triad: a case report].
AB  - The authors report a case of Currarino triad with a combination of anterior
      sacral meningocele and mature teratoma, sacral body deformity, anorectal
      stenosis, and tethered cord. A newborn girl suffered from vomiting, abdominal
      distension and constipation. Initially, a diverting colostomy was performed at
      the age of one month. 7 months later, at the age of 8 months, we performed
      posterior sagittal anorectoplasty (PSARP): As a result, extirpation of teratoma,
      excision of meningocele, untethering of the spinal cord, and anorectoplasty were
      achieved simultaneously without complication. We suggest the use of an MRI to
      specify the presence of anosacral and spinal cord anomalies in patients with
      intractable constipation and we recommend combined pediatric and neurosurgical
      assessment and management for all cases of Currarino triad.

PMID- 15462364
TI  - [Direct carotid approach for carotid angioplasty and stenting with a small
      incision: a technical case report].
AB  - Direct carotid puncture is an important option in endovascular surgery when a
      guiding catheter is not advanced into the common carotid artery because of
      arterial tortuosity. However, hemostasis after the procedure is not easy and
      hematoma formation from the puncture site sometimes causes serious complications.
      We present our carotid angioplasty and stenting (CAS) method with a direct
      carotid puncture and a small incision. An 85-year-old male with transient
      ischemic attack had severe left carotid artery stenosis. CAS was planned
      considering his age, but arterial tortuosity prevented a guiding catheter from
      being introduced into the left common carotid artery. Following this, the left
      common carotid artery was exposed with a small skin incision under local
      anesthesia, and a direct carotid puncture was made. A 7-French short sheath was
      carefully advanced and positioned into the left common carotid artery and a self
      expandable stent was delivered through it. Upon completion of the procedure, the
      puncture point of the vascular wall was sutured with 6-0 proline immediately
      after withdrawing the sheath, and the skin was closed. A direct carotid puncture
      with a small incision can be performed safely. This method can reliably stop
      bleeding from the puncture site and also avoid the need for prolonged manual
      compression of the carotid artery under systemic anticoagulation and antiplatelet
      therapy. We think our method is useful for accessing corotid artery stenosis when
      the transfemoral approach is difficult.

PMID- 15462365
TI  - [Case of painful tic convulsif: discussion of the underlying mechanisms and
      review of the literature].
AB  - The combination of trigeminal neuralgia and ipsilateral hemifacial spasm, known
      as painful tic convulsif (PTC), is a relatively rare entity in neurovascular
      compression syndrome. A case of PTC attributable to different offending arteries
      is described, the mechanisms and characteristics of PTC are discussed, and a
      review of the literature is presented. This 80-year-old woman had a 10-year
      history of left trigeminal neuralgia and ipsilateral hemifacial spasm. She
      presented with intermittent left facial twitching and pain, especially upon
      swallowing. MRI revealed compression of the left trigeminal nerve by the left
      anterior inferior cerebellar artery and of the ipsilateral facial nerve by the
      posterior inferior cerebellar artery. Microvascular decompression of the lesions
      via left lateral suboccipital craniotomy resulted in immediate and complete
      symptom improvement. Our case demonstrates that different arteries can affect the
      trigeminal and facial nerve at a stage that precedes compression by a tortuous
      vertebrobasilar artery. We suggest that the presence of PTC should be considered
      in patients with a tortuous vertebrobasilar artery, irrespective of the offending
      arteries.

PMID- 15462366
TI  - [Joint therapy of a dural arteriovenous fistula in the transverse-sigmoid sinus
      using surgical excision and direct sinus packing: a case report].
AB  - Combined therapy of direct sinus packing and surgical excision for intracranial
      dural arteriovenous fistula (dAVF) has not been reported in the literature. A 53
      year-old male was admitted to our hospital due to sudden onset of seizure and
      consciousness disturbance. Plain CT scan showed subcortical hematoma in the right
      temporal lobe. Cerebral angiography revealed dAVF involved in the right
      transverse and sigmoid sinuses. The lesion was associated with retrograde venous
      drainage into the right cerebellum, temporal, and occipital lobes. Positron
      emission tomography (PET) showed typical findings of venous hypertension in the
      involved areas. MRI also demonstrated a high intensity lesion in the medulla
      oblongata, suggesting critical venous congestion. First, we aimed to pack the
      involved sinus through a minor craniotomy, but cannulation into the sinus was
      impossible probably because of a marked fibrosis in the involved sinus. Then, we
      completely exposed the involved sinus through craniotomy. Through a microcatheter
      inserted into the sinus, the lower part of the sigmoid sinus was directly packed,
      and the remaining lesion was excised. Postoperative course was uneventful.
      Disappearance of dAVF resolved the findings on PET and MRI. Combined therapy
      would be a safe, non-invasive, and useful option for patients with a complex
      intracranial dAVF.

PMID- 15462367
TI  - [Superior sagittal sinus occlusion caused by a compound depressed skull fracture:
      a case treated by emergency surgery].
AB  - Depressed skull fractures compressing major venous sinuses are rare, and the
      treatment is a matter of controversy. The majority of depressed fractures are
      treated conservatively for fear of bleeding from venous sinuses, but surgical
      intervention was conducted in a few cases. We report a case of a 59-year-old man
      with a compound depressed fracture occluding the superior sagittal sinus (SSS).
      The patient was struck on the head by a heavy iron bar and admitted to our
      emergency center because of deterioration of consciousness. A computed
      tomographic scan showed depressed skull fracture overlying the SSS with
      hemorrhagic lesions in the bilateral parietal lobes and an acute epidural
      hematoma at the right temporoparietal convexity. Digital subtraction angiography
      (DSA) showed an occlusion of the SSS and compensatory venous drainage associated
      with poor capillary filling in the left parietal lobe. On an emergency basis,
      bone fragments compressing the SSS were surgically removed piece-by-piece to
      resolve severe venous congestion and to avoid infection. A small tear in the SSS
      was treated by head elevation and compressing the SSS with Gelfoam. Postoperative
      DSA confirmed the patency of the SSS and normal blood flow in the left parietal
      lobe. The patient exhibited slight disorientation and was transferred to another
      hospital for further rehabilitation. Because of symptomatic severe venous
      congestion, we had to perform emergency surgical decompression and removal of
      bone fragments. Treatment strategy for depressed skull fracture with SSS
      involvement was discussed with review of the literature.

PMID- 15462368
TI  - [Chronic electrical stimulation of the globus pallidus for treatment of
      Parkinson's disease].

PMID- 15462369
TI  - [Clinico-pathology of skull tumor: hemangioma, chordoma, hemangioendothelioma].

PMID- 15462370
TI  - [Elucidation of the pathogenesis of Parkinson's disease].

PMID- 15462371
TI  - [Progress in Parkinson's disease].
AB  - There has been lots of progress in Parkinson's disease. First of all, in Japan, a
      guideline for the treatment of Parkinson's disease was published. This guideline
      contains both EBM based systematic review of every drugs being used in the
      treatment of Parkinson's disease including those drugs for the management of side
      effects and other problems arising during the course of the treatment and an
      algorithm of the practical treatment of Parkinson's disease patients. This is an
      official publication of Japanese Neurological Society. In the diagnosis of
      Parkinson's disease, many specialists in Parkinson's disease have recognized the
      usefulness of MIBG SPECT of the cardiac sympathetic endings. MIBG uptake shows
      remarkable decrease in Lewy body positive Parkinson's disease patients from the
      early stage except for some of the stage I patients. In the basic aspect, studies
      on familial forms of Parkinson's disease have contributed a lot to the
      understanding of the pathogenesis of sporadic Parkinson's disease. Mutations of
      alpha-synuclein cause autosomal dominant Parkinson's disease. Recently,
      triplication of one of the alpha-synuclein genes was found as the third mutation
      of PARK1. Thus just overproduction of normal alpha-synuclein is toxic to nigral
      neurons. In this form and sporadic Parkinson's disease, oxidative damage plays an
      important role in nigral neurodegeneration. PARK2 is caused by mutations of the
      parkin gene. Parkin protein is an ubiquitin-protein ligase. In this form also,
      oxidative damage appears to be operating in neurodegeneration. Thus a common
      mechanism appears to be present in different forms of Parkinson's disease. Future
      investigation to find neuroprotective drugs should take this concept of common
      mechanism into their research strategies.

PMID- 15462372
TI  - [Parkinson's disease: the disease concept, etiology and diagnostic bases].
AB  - Parkinson's disease (PD) is caused by degeneration of nigral dopaminergic
      neurons. This results in dysfunction of the basal ganglia, thereby exhibiting
      movement disorders. The four cardinal signs of PD include bradykinesia, rigidity,
      resting tremor and postural instability. In the majority of patients with PD, the
      four cardinal signs are ameliorated by levodopa. In addition to anti-parkinson
      medication, surgery of the basal ganglia for PD has been applied. Local
      electrical stimulation of particular nuclei of the basal ganglia (deep brain
      stimulation) for PD has also proved to give satisfactory outcome. Both genetic
      and environment factors are considered to contribute to the initiation of PD.
      Some mutations of particular genes (e.g., alpha-synuclein) are found to link to
      parkinsonian families.

PMID- 15462373
TI  - [Essential points to differentiate various diseases causing parkinsonism].
AB  - This review article deals with the cardinal features to differentiate various
      conditions which present with parkinsonism other than Parkinson's disease.
      Special attention is paid to the distinctive clinical features, laboratory data
      and neuroimaging findings of frequent diseases as well as important ones
      including multiple system atrophy, progressive supranuclear palsy, corticobasal
      degeneration, Lewy body disease, drug-induced parkinsonism, vascular pseudo
      parkinsonism, normal pressure hydrocephalus and manganese intoxication due to
      parenteral nutrition. MRI is useful to diagnose MSA, vascular pseudo-parkinsonism
      and manganese intoxication. Benzamide derivatives including sulpiride and
      metoclopramide are the main causes of drug-induced parkinsonism in recent years
      in Japan.

PMID- 15462374
TI  - [Molecular biology for familial Parkinson's disease].
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorders.
      Recently, several forms of familial PD have been reported so far. Among them,
      several causative genes such as alpha-synuclein, UCH-L1, PINK1, and DJ-1 have
      been identified. Functional analysis on these causative genes may help us to
      explore the molecular mechanisms of nigral neuronal death in not only FPD but
      also sporadic form of PD. Thus, the identification of FPD gives us good
      information of etiologies of PD.

PMID- 15462375
TI  - [Analysis of alpha-synuclein and its significance].
AB  - Filamentous alpha-synuclein deposition is the defining hallmark of
      neurodegenerative synucleinopathies. The onset and progression of these diseases
      are thought to be related the formation of the alpha-synuclein filaments. We have
      analyzed posttranslational modifications of the filamentous alpha-synuclein in
      synucleinopathy brains by biochemical and protein chemical techniques. Mass
      spectrometric analysis revealed that deposited alpha-synuclein is highly
      phosphorylated at Ser129. We also found that alpha-synuclein is ubiquitinated in
      several synucleinopathy brains. The ubiquitination sites of soluble and
      filamentous alpha-synuclein were determined. These data have important
      implications for understanding the formation of alpha-synuclein filaments in
      synucleinopathy brains.

PMID- 15462376
TI  - [Mechanism of specific dopaminergic neuronal death in Parkinson's disease].
AB  - Parkinson's disease (PD) is characterized by progressive degeneration of
      dopaminergic (DAergic) neurons of the nigrostriatal system, with resulting
      reduction in striatal dopamine (DA) concentration. Various mechanisms have been
      implicated in the pathogenesis and progression of PD. Among them, mitochondrial
      dysfunction, inflammation and oxidative stress had been accepted as the most
      plausible mechanism of disease progression. The free radicals/oxidative stress
      produced by MPTP, 6-hydroxydopamine, rotenone, activated microglias, and
      disturbances in mitochondrial respiratory enzymes provide a common pathway for
      the progression of all kinds of neurons. On the other hand, numerous studies on
      DA-induced neurotoxicity have been reported recently, and DA itself exerts
      cytotoxicity in DAergic neurons mainly due to the generation of highly reactive
      DA -quinones which are DAergic neuron-specific cytotoxic molecules. DA quinones
      may irreversibly alter protein function through the formation 5-cysteinyl
      dopamine on the protein. For example, the formation of DA quinone-alpha-synuclein
      complex consequently increases cytotoxic protofibrils and covalent modification
      of functional enzymes. Thus, DA quinones play an important role in 'specific'
      DAergic neuro-degeneration of PD.

PMID- 15462377
TI  - [Searching genetic risk factors for sporadic Parkinson's disease].
AB  - Multiple genetic and environmental factors are thought to cause idiopathic
      Parkinson's disease (PD). To identify the genetic factors, we are carrying case
      control association studies by genome-wide MS (microsatellite) markers and SNP
      (single nucleotide polymorphism) markers on the candidate genes, and sib-pair
      analysis. We investigated 27,000 MS markers and found 8% of them were
      significantly associated with PD in the first screening. In the candidate gene
      approach, of 267 SNPs on 122 candidate genes, 22 SNPs on 16 genes showed
      significant p-values (less than 0.05) by chi-square statistics. The further
      analysis is necessary to identify causative genes for PD.

PMID- 15462378
TI  - [ES cell therapy for Parkinson's disease].
AB  - Neural transplantation, as a treatment for advanced Parkinson's disease (PD), has
      been studied for more than a decade due to the potential replacement of
      degenerated dopaminergic (DA) neurons. Several open-label studies on implantation
      of fetal nigral neurons revealed improvement in motor functions. However, the
      benefits were incomplete in double-blind trials. Progressive neural or embryonic
      stem (ES) cell research has raised hopes of creating novel cell replacement
      therapies for PD. DA neurons have been efficiently produced from primate ES cells
      in astrocyte-conditioned medium. Transplantation of neuronal stem cells derived
      from primate ES cells into a primate model of PD restored striatal DA function,
      suggesting ES cells are suitable donor cells.

PMID- 15462379
TI  - [Gene therapy for Parkinson's disease].
AB  - Recent advances in gene transfer methods, especially development of a high titer
      recombinant adeno-associated viral (AAV) vector, are making gene therapy for
      Parkinson's disease (PD) a feasible therapeutic option in the clinical arena.
      Efficient and long-term expression of genes for dopamine (DA)-synthesizing
      enzymes in the striatum restored local DA production and allowed behavioral
      recovery in animal models of PD. Moreover, sustained expression of a glial cell
      line-derived neurotrophic factor gene in the striatum rescued nigral neurons and
      led to functional recovery in a rat model of PD, even when treatment was delayed
      until after the onset of progressive degeneration. A clinical trial to evaluate
      the efficacy of subthalamic transduction to produce inhibitory transmitters is
      underway.

PMID- 15462380
TI  - [The pharmacological and rational theory for the drug development of Parkinson's
      disease].
AB  - The basal ganglia in the brain contains glutamate, dopamine, serotonin,
      noradrenaline, CCK, adenosine, opioid, cannabinoid, etc. These agents contribute
      to keep motor control and modulation of the agent may be a cue to the treatment
      of movement disorders. D1 or D2 dopamine receptor agonists increase locomotor
      activity in MPTP-treated common marmosets which showed decreased locomotor
      activity and decreased number of dopamine neurons in the substantia nigra. Using
      this model of parkinsonism, NMDA receptor antag-onists, antimuscarinic receptor
      antagonists, 5-HT1A receptor agonists, adenosine receptor antagonists were showed
      to reverse the impaired movement of the model animals. The results may contribute
      to the development of new drugs for the treatment of Parkinson's disease.

PMID- 15462381
TI  - [Depression in Parkinson's disease].
AB  - Depression is a common symptom in Parkinson's disease (PD) and its frequency is
      about 40%. But, frequency of major depression in PD is about 2.2-7.7% and similar
      to age-matched aged group. Depressive state (depression), not major depression,
      is an essential feature of PD derived from impairment of mesocortico-frontal
      dopaminergic pathway. But, PD has many impaired neurotransmitter systems
      including dopamine, serotonin and noradrenaline. As a neurochemical background is
      complicated, we have not yet drugs for depression in PD.

PMID- 15462382
TI  - [Sleep disorders in Parkinson's disease].
AB  - Approximately 74-94% patients with Parkinson's disease have sleep disorders: such
      as frequent awakening, excessive daytime sleepiness, nightmares, nocturnal
      cramps, REM sleep behavior disorders and so on. In contrast, the relationship
      between physiological mechanism of sleep and the dopamine systems are still
      obscure, because the dopamine systems are not directly related neither initiating
      or maintaining sleep system nor awaking system. However, most of all the
      dopaminergic drugs were reported to induce sleepiness or sleep attacks in the
      patients with Parkinson's disease. So, physicians must inform patients with
      Parkinson's disease warning the excessive daytime sleepiness and sleep attack. In
      this article, I suggest the mechanisms of sleep disorders on Parkinson's disease
      from the physiological points of view, and how to manage these problems.

PMID- 15462383
TI  - [Behavioral impairments in Parkinson's disease].
AB  - Behavioral impairments in parkinsonian patients include agitation,
      hypersexuality, stereotypic movement, pathological gambling, abuse of
      antiparkinsonian drugs, REM sleep behavioral disorder, and restless legs
      syndrome. Dementia, psychoses, and emotional disorders, such as depression and
      anxiety/panic disorder, also impair behavior. Symptoms may be produced by
      dysfunction of the central nervous system, medication, and/or the psychosocial
      problems associated with Parkinson's disease. Treatment therefore should be based
      on the cause of the symptoms seen. In some cases, the reduction or change of
      antiparkinsonian drugs, or both, may be effective. Treatment of the motor
      symptoms of Parkinson's disease, including motor fluctuations, may reduce the
      risk of panic attacks being evoked in the 'off' period. Use of antidepressants,
      sedatives, and neuroleptics may often be effective. Physicians should identify
      the causes of the symptoms of behavioral impairment and select appropriate
      treatments.

PMID- 15462384
TI  - [The cognitive dysfunction in Parkinson's disease].
AB  - Parkinson's disease (PD) is a slowly progressive disorder which begins with motor
      symptoms. Several cognitive deficits can be observed in nondemented patients with
      PD during their history. The core symptom in the cognitive deficits in PD is the
      executive dysfunction. Neuropsychological tests such as Wisconsin Card Sorting
      Test, Trail Making Test are used to measure the degree of this dysfunction.
      Executive dysfunction is thought related to abnormalities in the dorsolateral
      prefrontal circuit which largely passes through the caudate nucleus. The
      dysfunction emerges as the pathology spreads to the nigrocaudate project
      corresponding to Hoehn & Yahr stage II-III. Effective therapy for cognitive
      dysfunction in PD remains elusive, however donepezil, Attention Process Training,
      Music therapy and Transcranial magnetic stimulation have been reported to have
      partial efficacy.

PMID- 15462385
TI  - [Stereotactic operation for Parkinson's disease].
AB  - The aim of stereotactic operation for Parkinson's disease is to improve or keep
      daily activity or quality of life by ablation or improvement of some parkinsonian
      symptoms. All of parkinsonian symptoms are not improved by stereotactic operation
      and classify roughly into three categories. The symptoms which are definitely
      improved are tremor, rigidity, L-dopa-induced dyskinesia, bradykinesia (secondary
      bradykinesia caused by rigidity) and wearing off phenomenon. Freezing gait,
      postural instability or postural abnormality is improved in some patients, but
      not always. Disturbance of speech or swallowing, L-dopa non-responsive akinesia,
      psychiatric symptoms or autonomic disturbances are not expected to be improved.
      Before stereotactic operation symptoms which cause disabilities of patients
      should be carefully examined. Aim of stereotactic operation should make clear and
      not ambiguous.

PMID- 15462386
TI  - [Indication of surgical therapy for Parkinson's disease].
AB  - We review the current status of surgical treatment of Parkinson's disease (PD).
      The advantages of deep brain stimulation (DBS) over ablative surgery include
      reversibility and controllability of stimulation. In addition, DBS carries a
      smaller risk of side effects, especially when employed bilaterally. DBS of the
      thalamus is useful to control tremor which is unresponsive to medication. DBS of
      the globus pallidus internus (GPi) or the subthalamic nucleus (STN) is useful to
      control wearing off of motor symptoms which is difficult to manage with
      medication alone. DBS of STN and GPi improves motor function mainly during the
      off-period. DBS of STN attenuates levodopa-induced dyskinesia through reduction
      of dopa requirement, whereas DBS of GPi attenuates dopa-induced dyskinesia
      directly. DBS of STN is also useful to control symptoms of PD in patients who are
      intolerant to dopa. However, DBS of either STN or GPi cannot reverse advanced
      symptoms of PD, which are unresponsive to dopa.

PMID- 15462387
TI  - [Quality of life in Parkinson's disease].
AB  - Assessing quality of life (QOL) is now essential for making clinical, economic,
      social, and political decisions. QOL is multi-dimensional, subjective, and
      context-dependent. It can encompass physical aspects of living, activities in
      daily life, communication with other people, spiritual existence, and more.
      Parkinson's disease is a chronic progressive disease that affects many organ
      systems. Complete descriptions of QOL outcomes in patients with Parkinson's
      disease include both qualitative-narrative methods and quantitative scales.
      Assessing QOL in clinical practice can help clinicians improve patients' lives.

PMID- 15462388
TI  - [Treatment for patients with early Parkinson's disease].
AB  - Ad hoc committee of Japanese Neurological Society made a guideline for the
      treatment of Parkinson's disease in 2002. Based on the chapter of treatment for
      early Parkinson's disease, starting drugs were discussed in this article. Three
      points should be considered in initiating the drug treatment, that is,
      neuroprotection, motor complications, and side effects. In order to demonstrate
      neuroprotection of dopamine agonists by using neuroimaging techniques, CALM-PD
      CIT study (pramipexole) and REAL-PET study (ropinirole) were done. There are,
      however, many controversies concerning neuroprotection and no definite conclusion
      was drawn. On the contrary, the inhibitory effects of dopamine agonists on the
      appearance of motor complications were clearly elucidated by several large-scale
      studies. For the present, although the side effects were reported more frequently
      in those treated by dopamine agonists than by levodopa, starting the treatment by
      dopamine agonists were recommended except in patients with dementia and in
      elderly patients, for whom levodopa should be used first.

PMID- 15462389
TI  - [Medical treatment of dyskinesia].
AB  - Dyskinesia and dystonia are common complications of long-term levodopa therapy.
      Because peak-dose dyskinesia is due to excessive dopaminergic stimulation by anti
      parkinsonian drugs, it is solved by reducing the whole dose or by taking frequent
      small doses of levodopa in order to keep relatively stable serum levels. It may
      be attenuated by dopamine receptor agonists or amantadine which acts as an N
      methyl-D-aspartate (NMDA) receptor agonist. On the other hand, since early
      morning dystonia is related to the decline in the level of levodopa, it is
      initially treated by adding a small dose of levodopa in bedtime. Other patterns
      of dystonia are often treated accordingly to the treatment of wearing-off
      phenomenon.

PMID- 15462390
TI  - [The therapy of wearing-off].
AB  - Wearing-off, predictable end of dose deterioration, is one of the major problems
      of long-term levodopa treatment for Parkinson's disease. The mechanisms of
      wearing-off are (1) loss of striatal dopamine storage, (2) change in the
      peripheral pharmacokinetics of levodopa and (3) modification of dopamine
      receptors. The main therapeutic strategy for wearing-off is continuous
      stimulation of dopamine system. For this purpose, we increase frequency of
      levodopa doses and use long half-life dopamine agonist(continuous stimulation of
      dopamine receptors), COMT inhibitor and MAOB inhibitor (prolongation of the half
      life of levodopa and dopamine), and zonisamide (long-term increase of dopamine
      synthesis).

PMID- 15462391
TI  - [Prevention and treatment of malignant syndrome in patients with Parkinson's
      disease].
AB  - This article summarizes the prevention and treatment of malignant syndrome (MS)
      in Parkinson's disease. MS is often induced by sudden withdrawal of levodopa.
      However, many other events can be responsible for the induction of MS, including
      concomitant infections, dehydration, hot weather, discontinuation of other
      antiparkinsonian drugs, and 'wearing off' phenomenon. MS should be suspected when
      the body temperature rises above 38 degrees C without an apparent cause. The
      early detection and its prompt commencement of treatment are essential for
      improving the prognosis of the disease. The treatment consists of ample
      intravenous fluid, cooling the body, antiparkinsonian drugs (particularly,
      levodopa and bromocriptine), dantrolene sodium, and antibiotics if infection is
      present.

PMID- 15462392
TI  - [The recent advance of treatment of Parkinson's disease].
AB  - The primary pathology of Parkinson's disease is the degeneration of dopaminergic
      neurons in the nigrostriatal pathway, resulting in a significant reduction in
      striatum dopamine concentration which is responsible for the altered motor
      functions. With time and disease progression, efficacy of dopaminergic therapy
      becomes unpromising. We herein review the recent advance of treatment of
      Parkinson's disease to prevent ongoing progressive nature of Parkinson's disease.

PMID- 15462393
TI  - [Support of home care and rehabilitation].
AB  - With the aging of society in Japan, the figure of Parkinson's disease is
      gradually increasing and the percentage of patients with severe disease has also
      increased. Among intractable neurological diseases, the possibility of bed
      confinement is the highest for this disease. Therefore, in addition to
      appropriate control of the disease using anti-parkinsonism drugs, maintenance of
      QOL, rehabilitation, the daily life therapy and treatment at home are necessary
      in terms of long-term management. Treatment at home combined with persons who
      care for the patient and in cooperation with other welfare resources may improve
      the patient's QOL. In diseases that require long-term care such as Parkinson's
      disease, a comprehensive care management system should be established from the
      aspect of the patient's QOL.

PMID- 15462394
TI  - [Diagnostic use of functional imaging in Parkinson's disease and related
      disorders].
AB  - We reviewed the roles of functional neuroimaging in the diagnosis of Parkinson's
      disease and related disorders. Positron emission tomography or single photon
      emission computed tomography measurements in combination with various markers for
      brain metabolism and pre- and post-synaptic dopamine systems have a potential to
      enhance an accurate pre-mortem diagnosis of akinetic-rigid syndrome. Using
      information from magnetic resonance imaging technique seems helpful, too.
      Furthermore, these methods appear to be useful in pre-morbid diagnosis of
      Parkinson's disease and longitudinal follow-up for reassessing the rationality of
      treatment. The sensitivity and specificity of these diagnostic tools still wait
      for future evaluation, and we foresee further refinement of imaging and analytic
      methods.

PMID- 15462395
TI  - [Inhibition of relapse in leukemia by using molecular targeting therapy].
AB  - Leukemias are generally chemosensitive, and a majority of leukemia patients
      undergo remission. However, since chemotherapy after remission generally causes
      gross systemic toxicity, patients cannot be administered enough anti-cancer drugs
      to be completely cured; thus, the rate of long-term disease-free survival remains
      low. Improved survival requires new strategies to prevent relapse. Molecular
      targeting therapies are remarkably specific and have been demonstrated to cause
      no gross systemic toxicity. Molecular targeting drugs for leukemia such as all
      trans retinoic acid and imatinib are presently being used in clinical settings,
      and many other molecular targeting drugs are being evaluated in phase I/II
      clinical trials. This review presents an overview of some of these drugs.

PMID- 15462396
TI  - [Improvement of QOL by drug delivery systems].
AB  - The objectives of the medical advancements made in recent years are i) the cure
      of diseases and relief of their symptoms, ii) expansion of life expectancy, iii)
      improvement of QOL (quality of life), and iv) prevention of diseases. Most
      importantly, the therapy should maintain the dignity of patients. DDS is defined
      as a highly-functional dosage form for improving the medical usefulness of drugs
      by potentiating their efficacy, reducing their toxicity, and making them a
      'patient-friendly medicine'. DDS is strongly expected for achieving 1) the
      controlled release, 2) new alternative mucosal absorption, and 3) targeting to
      the action site of drugs. The improvements of QOL by devising novel DDS such as
      Lupron Depot, Imigran Nasal Spray, Durotep Patch and Pegasys were reviewed.

PMID- 15462397
TI  - Antisense targeting in cell culture with radiolabeled DNAs--a brief review of
      recent progress.
AB  - The promise of antisense targeting that any tissue with a unique genetic
      expression can be specifically localized with radioactivity in the living subject
      is the holy grail that drives this research today. If antisense targeting were to
      achieve even a fraction of its promise, the results could well lead a revolution
      in diagnostic nuclear medicine. Despite its obvious complexities, antisense
      targeting with radiolabeled oligomers such as DNA is making considerable progress
      in cell culture. As is documented in this brief review, evidence is becoming
      overwhelming that an antisense mechanism is probably responsible for the
      accumulation in tumor cells in culture of radiolabeled DNAs with base sequences
      antisense to target messenger RNAs (mRNAs). That an increased accumulations of
      these DNAs compared to control DNAs has now been seen in a substantial number of
      tumor cell types and mRNA targets largely eliminates any possibility of an
      aptameric effect being responsible for these specific accumulations. In addition,
      the number of antisense DNAs accumulating specifically in cells in culture has
      been shown to be orders of magnitude larger than that expected on the basis of
      steady state mRNA levels. Thus, two of the main concerns regarding antisense
      targeted, namely that the mechanism of localization may not be attributed to
      antisense and that the degree of accumulation will be impractically low for
      imaging, have been addressed in recent research. The remaining obstacle to
      successful targeting may be delivery. This review will provide a brief review of
      recent results, primarily from the laboratory of one of the authors (DJH),
      obtained in tissue culture in studies of antisense targeting and will conclude
      with several suggestions for future approaches.

PMID- 15462398
TI  - Clinical significance of cerebrovascular reserve in acetazolamide challenge 
      comparison with acetazolamide challenge H2O-PET and Gas-PET.
AB  - OBJECTIVE: The response of cerebral blood flow (CBF) to acetazolamide (ACZ)
      challenge is frequently determined in clinical settings to evaluate
      cerebrovascular reserve (CVR). A reduced CVR can indicate patients with occlusive
      cerebrovascular disease and compromised hemodynamics who may be at increased risk
      of cerebral ischemia. However, how precisely ACZ reflects cerebral hemodynamic
      impairment remains obscure. The present study aims to clarify the pathological
      significance of CVR in patients with occluded carotid arteries. METHODS: We
      recruited seventeen patients with occlusive lesions in the internal carotid
      artery (ICA) or middle cerebral artery (MCA). We assessed these patients in terms
      of resting cerebral blood flow (CBF) and the CVR response to ACZ challenge using
      H20 positron emission tomography (PET). In addition, we evaluated hemodynamic
      parameters including oxygen extraction fraction (OEF) using Gas-PET. RESULTS: We
      identified a significant negative correlation between the CVR and OEF or the
      cerebral blood volume (CBV)/CBF ratio, as a potential index of cerebral perfusion
      pressure. Although the CVR values were reduced in all regions with elevated OEF
      (Stage II), these values were highly variable regardless of the CBV/CBF ratios.
      The cut-off value of CVR alone could not detect Stage II, but when combined with
      resting CBF, misery perfusion accompanied by increased OEF was detected with high
      sensitivity (6/7) and specificity (61/62). CONCLUSION: CVR could be applied as an
      index reflecting both autoregulatory capacity and OEF. The present study also
      supported the notion that SPECT with ACZ challenge can be clinically applied to
      detect misery perfusion.

PMID- 15462399
TI  - Clinical usefulness of ECG-gated 18F-FDG PET combined with 99mTC-MIBI gated SPECT
      for evaluating myocardial viability and function.
AB  - OBJECTIVES: This study sought to evaluate an imaging approach using gated 99mTc
      MIBI (MIBI) SPECT and gated 18F-FDG (FDG) PET for assessment of myocardial
      viability and cardiac function. METHODS: Forty-eight patients (38 men, mean age
      68.1 +/- 9.6 years) underwent ECG-gated FDG PET and MIBI SPECT within a week. The
      baseline diagnoses were coronary artery disease (31), mitral regurgitation (1),
      paroxysmal arrhythmia (10), and dilated cardiomyopathy (6). The gated FDG PET
      data were analyzed using pFAST software, and the gated MIBI SPECT data were
      analyzed using QGS software. Fifteen patients were diagnosed with myocardial
      infarction, and follow-up study was performed to assess the functional outcome
      four months later. An improvement in LVEF of >5% was defined as significant. The
      LV myocardium was divided into 17 segments, and regional defect scores were
      visually assessed using a 4-point scale for each segment (0 = normal, 1 = mildly
      reduced, 2 = moderately reduced, 3 = absent). A segment with a greater defect
      score on MIBI SPECT than on FDG PET was defined as a mismatch. The patients were
      divided into two groups: those with at least two mismatched segments (MM-group),
      and those with none or one (M-group). RESULTS: LVEF, EDV and ESV measured by
      gated FDG PET were highly correlated with those obtained by gated MIBI SPECT (r =
      0.848, 0.855 and 0.911, p < 0.0001, respectively). The mean values of LVEF did
      not differ significantly, but EDV and ESV obtained by gated FDG PET were
      significantly grater than those obtained by gated MIBI SPECT (p < 0.0001). In 15
      patients diagnosed with myocardial infarction, a significant association (p <
      0.05) was found between the relative uptake of FDG PET and MIBI SPECT and the
      functional outcome 4 months later. Global LV function improved in 6 of the 8
      patients showing mismatch but in only 1 of the 7 patients with matched defects,
      resulting in a sensitivity of 86% and specificity of 75%. The overall accuracy to
      predict global functional outcome was high (80%). CONCLUSION: This imaging
      approach allows accurate evaluation of myocardial viability. Furthermore, the
      high correlations of gated FDG PET and gated MIBI SPECT measurements hold promise
      for the assessment of left ventricular function using gated FDG PET.

PMID- 15462400
TI  - Attenuation correction using combination of a parallel hole collimator and an
      uncollimated non-uniform line array source.
AB  - Attenuation correction is very important for quantitative SPECT imaging. We
      designed an uncollimated non-uniform line array source (non-uniform LAS) for
      attenuation correction based on transmission computed tomography (TCT) using Tc
      99m and compared its performance with an uncollimated uniform line array source
      (uniform LAS) in a thorax phantom study. This non-uniform LAS was attached to one
      camera head of a dual-head gamma camera, and transmission data were acquired with
      another camera head with a low-energy, general purpose, parallel-hole collimator
      at 50 cm-distance apart from the source. The modified TEW using a subtraction
      factor of 1.0 was employed to correct scattered Tc-99m photons for transmission
      data. In the phantom experiment, eight TCT data were acquired with the scanning
      time changed from 2 minutes to 20 minutes for each LAS. The Tc-99m attenuation
      coefficient (mu) maps with the non-uniform LAS and uniform LAS improved the
      statistical count variation in the mediastinum filled with water as the scanning
      time got longer. The Tc-99m mu-map with the non-uniform LAS and 6 minutes of
      scanning time had equal quality at the center of the thorax phantom to that with
      the uniform LAS and 16 minutes of scanning time. In conclusion, for the TCT
      imaging with combination of the parallel hole collimator and uncollimated Tc-99m
      external source the non-uniform LAS can reduce the Tc-99m radioactivity or the
      TCT scanning time compared with the uniform LAS.

PMID- 15462401
TI  - Lung hilar Ga-67 uptake in patients with lymphoma following chemotherapy.
AB  - Scintigraphic characteristics of lung hilar Ga-67 uptake (HU) and their
      relationship with the etiology (benign vs. malignant) of the hilar lesions in
      lymphoma patients following chemotherapy were retrospectively investigated. A
      total of 161 lymphoma patients were included in the study. The presence/absence
      of HU and if present, symmetry/asymmetry and intensity of HU (on the basis of a 3
      scale grading system) were visually and semiquantitatively assessed on transaxial
      sections of thorax Ga-67 SPECT. By drawing ROIs over right and left hilum,
      asymmetry index (AI%) was also calculated. HU was categorized as benign or
      malignant depending on the radiological correlation and clinical follow-up. In
      the malignant group, the majority of patients (85.7%) had grade 2 or grade 3
      uptake and all had asymmetric pattern. However, in the benign group, grade 1
      uptake was more common (66%) and was mainly symmetric (94.6%) in appearance. AI%
      in the malignant group (73.7 +/- 36.6) was significantly higher than in the
      benign group (5.7 +/- 4.9) confirming the marked asymmetry in malignant patients.

PMID- 15462402
TI  - Evaluation of mandibular invasion by head and neck cancers using 99mTc-methylene
      diphosphonate or 99mTc-hydroxymethylene diphosphonate and 201Tl chloride dual
      isotope single photon emission computed tomography.
AB  - Whether a patient with head and neck cancer has mandibular invasion or not is
      important in determining the method of resection surgery. But, no modality is
      adequately reliable when used alone in the evaluation of mandibular invasion.
      Therefore, to more accurately diagnose mandibular invasion in head and neck
      cancer, we used a new modality, namely, 99mTc methylene diphosphonate (MDP) or
      99mTc hydroxymethylene diphosphonate (HMDP) and 201Tl chloride dual isotope
      single photon emission computed tomography (Tc/Tl SPECT). The aim of this study
      is to disclose the usefulness of Tc/Tl SPECT in the assessment of mandibular
      invasion by head and neck cancers. 99mTc-MDP or -HMDP SPECT (Tc SPECT)s and 201Tl
      chloride SPECT (Tl SPECT)s were performed in 34 patients with suspected
      mandibular involvement of head and neck cancer. Thirty of 34 cases underwent both
      TcMTl SPECT and CT examination. Tc/Tl SPECT fusion images were obtained using the
      Automatic Registration Tool (ART, TOSHIBA, Japan) system. In the diagnosis of
      mandibular invasion on Tc/Tl SPECT fusion images, a problem was that the range of
      Tc and Tl uptake was changed by the condition of display used in the
      reconstruction and expression of the images. Then, prior to clinical evaluation,
      to reveal the most appropriate upper window level for display, a phantom study
      was performed. In a clinical study, the upper window level was set at 40 or 50%,
      which were verified to be the proper values in the preliminary study. The
      diagnostic accuracy obtained using Tc SPECT, TcMTl SPECT and CT was compared with
      the histopathological findings. Tc/Tl SPECT at 40 and 50% upper window level had
      higher specificity, accuracy, and positive predictive value (73.3%, 85.3%, 81.8%)
      than Tc SPECT alone (21.4%, 67.6%, 64.5%) and higher sensitivity and negative
      predictive value (94.7%, 91.7%) than CT (70.6%, 72.2%) for detecting mandibular
      invasion. Tc/Tl SPECT was a useful diagnostic procedure for the assessment of
      mandibular invasion by head and neck cancers.

PMID- 15462403
TI  - Positron emission tomographic imaging with 11C-choline in differential diagnosis
      of head and neck tumors: comparison with 18F-FDG PET.
AB  - The aim of this study was to evaluate the clinical value of positron emission
      tomography (PET) with 11C-labeled choline (CHOL) for the differential diagnosis
      of malignant head and neck tumors from benign lesions as compared with 18F
      fluorodeoxyglucose PET. METHODS: We studied 45 patients (28 males, 17 females,
      age range, 29-84 years) with suspected lesions in the head and neck region using
      both CHOL and FDG PET within a 2-week period on each patient. All patients fasted
      for at least 6 hours for both the CHOL and FDG studies. PET imaging was performed
      5 min and 50-60 min after intravenous injection of CHOL and FDG, respectively.
      After data acquisition, PET images were corrected for attenuation, and the
      reconstructed images were analyzed by visual interpretation. Then, the
      standardized uptake value (SUV) was calculated for semiquantitative evaluation of
      tumor tracer uptake. Finally the results of PET scans were compared with the
      histological diagnoses from surgical specimens or biopsies. RESULTS: With CHOL
      PET, malignant tumors were correctly detected in 24 (96%) of 25 patients, and
      benign lesions in 14 (70%) of 20 patients with an accuracy of 84.4%. With FDG
      PET, malignancy was correctly diagnosed in 23 (92%) of 25 patients, and benign
      lesions in 13 (65%) of 20 patients resulting an accuracy of 80%. A significant
      positive correlation between CHOL and FDG SUVs was found for all lesions (r =
      0.677, p = 0.004, n = 45). Malignant tumors showed significantly higher tracer
      accumulation than the benign lesions in both CHOL and FDG studies (5.69 +/- 1.61,
      n = 25 vs. 2.98 +/- 2.13, n = 20, p < 0.0001; 9.21 +/- 4.23, n = 25 vs. 3.60 +/-
      2.57, n = 20, p < 0.0001). The cutoff SUV for differentiating malignant and
      benign lesions was 3.5 for CHOL and 3.9 for FDG. CHOL showed slightly better
      differentiation between malignant and benign lesions than FDG although some
      overlap existed on both studies. But the difference was not statistically
      significant. CONCLUSION: The results of this study indicate that CHOL PET may be
      feasible clinically for head and neck tumor imaging. PET imaging with CHOL seems
      to be able to detect malignant head and neck tumors as effectively as FDG PET.
      The advantages of CHOL PET were shorter examination period and low uptake in the
      muscle. However, both CHOL and FDG have some limitations in the evaluation of
      salivary gland lesions.

PMID- 15462404
TI  - Assessment of the optimal time interval and background region of interest in the
      measurement of differential renal function in Tc-99m-EC renography.
AB  - BACKGROUND: Differential renal function (DRF) measurements are routinely
      corrected for background, which mainly affects the reproducibility and accuracy
      of the measurement. The present study was conducted to identify the most
      appropriate background ROI and optimal time interval in the calculation of DRF
      for EC renography. MATERIALS AND METHODS: Nineteen patients were studied. For
      determination of DRF in EC renography, the selected time intervals were 0.5-1.5;
      0.5-2; 1-2; 1.5-2.5; 2-3 min, and the background ROI types were inferolateral
      crescent, lateral crescent, and perirenal shaped. The reference DRF was obtained
      through DMSA study. For low functioning kidney of each patient, relative uptake
      differences between the DMSA and EC scans were calculated. Then, the mean
      differences and the standard deviations were found. RESULTS: The highest
      correlation was between the DRF values obtained using inferolateral background
      ROI in 0.5-2 minutes of EC scintigraphy and the DRF values obtained through
      posterior DMSA images (r = 0.9889). However, there were no statistically
      significant differences between the mean DRF values obtained for each time
      interval with each ROI type (p > 0.05). For all the time intervals and background
      ROIs, the mean of the differences was <0.9%. In conclusion, in obtaining
      comparable DRF values from EC and DMSA studies, none of the background types
      proved superior. Also our research for optimal time interval showed that EC
      scintigraphy underestimates the DRF when compared to DRF obtained from DMSA
      study. The DRF has a tendency to decrease as the later time intervals are used.
      The time intervals less than 2.5 minutes show lower underestimation of DRF
      values.

PMID- 15462406
TI  - Semi-quantitative assessment of oral cavity squamous cell carcinoma using 201Tl
      SPECT for evaluating effectiveness of preoperative radiotherapy.
AB  - The aim of this study is to reveal the usefulness of semi-quantitative assessment
      using 201Tl chloride (Tl) single photon emission computed tomography (SPECT) (Tl
      SPECT) to evaluate the effectiveness of radiotherapy in 15 patients with oral
      cavity squamous cell carcinma (SCC). Fifteen patients were diagnosed with SCC by
      biopsy. All 15 patients enrolled in this study were planned to undergo
      preoperative radiotherapy with or without chemotherapy using carboplatin (CBDCA)
      and received reduction operation. Tl SPECTs were performed 15 minutes after
      intravenous administration of 111 MBq 201Tl chloride. Regions of Interest (ROI)
      were set up around tumor (T), and non-lesion (N) at the part of contralateral
      scalp at the height of the cerebellum. The ratios of mean counts in ROI of the
      tumor to those in non-lesion were measured as pre- and post-treatment T/N ratios
      (pre T/N, post T/N). Furthermore, reduction rate (RR) was obtained by calculating
      [(pre T/N - post T/N)/(pre T/ N)] x 100%. Each parameter (pre T/N, post T/N, and
      RR) was compared to histopathological grade of surgical specimen based on the
      Oboshi and Shimosato classification (grade I-IV). RR showed significantly higher
      values in grade III and IV than in grade I and II (p = 0.0008). In conclusion,
      semi-quantitative assessment using Tl SPECT, especially calculating RR, is useful
      to evaluate the effectiveness of preoperative radiotherapy.

PMID- 15462405
TI  - An application of a new planar positron imaging system (PPIS) in a small animal:
      MPTP-induced parkinsonism in mouse.
AB  - OBJECTIVE: Recent animal PET research has led to the development of PET scanners
      for small animals. A planar positron imaging system (PPIS) was newly developed to
      study physiological function in small animals and plants in recent years. To
      examine the usefulness of PPIS for functional study in small animals, we examined
      dopaminergic images of mouse striata in MPTP-induced parkinsonism. METHODS: Male
      C57BL/6NCrj mice were treated with MPTP 7 days before the PPIS study. Scans were
      performed to measure dopamine D1 receptor binding and dopamine transporter
      availability with [11C]SCH23390 (about 2 MBq) and [11C]beta-CFT (about 2 MBq),
      respectively. After the PPIS study, dopamine content in the striatum was measured
      by HPLC. RESULTS: The MPTP treatment significantly reduced dopamine content in
      the striatum 7 days after treatment. In the MPTP-treated group, [11C]beta-CFT
      binding in the striatum was significantly decreased compared with the control
      group, while striatal [11C]SCH23390 binding was not affected. Dopamine content in
      the striatum was significantly correlated with the striatal binding of [11C]beta
      CFT. CONCLUSION: The present results suggest that PPIS is able to determine brain
      function in a small animal. Using PPIS, high throughput imaging of small animal
      brain functions could be achieved.

PMID- 15462407
TI  - Metastatic insular thyroid carcinoma: visualized on Tc-99m pertechnetate, Tc-99m
      MDP and iodine-131 scintigraphy; a review of the literature for other
      radionuclide agents.
AB  - Poorly differentiated insular thyroid carcinoma is classified as a separate
      entity among other tumors of the thyroid gland. Its histological pattern and
      clinical course are regarded as intermediate between well-differentiated and
      anaplastic thyroid cancer. The authors report Tc-99m pertechnetate, Tc-99m MDP
      and radioiodine imaging features in a 33-year-old male patient with metastatic
      insular carcinoma of the thyroid. The extent of involvement was almost identical
      in all three studies. Insular carcinoma of the thyroid was shown by biopsy, and
      the patient received a cumulative dose of 14,800 MBq (400 mCi) radioactive I-131.
      Other radionuclide imaging agents are also reviewed.

PMID- 15462408
TI  - Comparison of FDG-PET and IMP-SPECT in patients with dementia with Lewy bodies.
AB  - OBJECTIVES: To investigate regional differences in cerebral glucose metabolism
      and blood flow of dementia with Lewy bodies (DLB), we studied 7 subjects with DLB
      and 20 normal controls using F-18 fluorodeoxyglucose (FDG) and positron emission
      tomography (PET) and then examined the same 7 subjects and 20 other normal
      controls with I-123 iodoamphetamine (IMP) and single photon emission computed
      tomography (SPECT). METHODS: The anatomically standardized images were produced
      with NEUROSTAT and the regional relative metabolic and perfusional values were
      calculated. RESULTS: The mean reduction ratios of FDG uptake in the DLB group
      relative to the mean normal controls in the parietal lobe and occipital lobe were
      0.72 and 0.83, respectively, while the corresponding mean reduction ratios of IMP
      uptake were 0.81 and 0.88, respectively. In the DLB group, parietal FDG uptake
      was significantly lower than parietal IMP uptake (p < 0.05), occipital FDG uptake
      was significantly lower than occipital IMP uptake (p < 0.05), and parietal IMP
      uptake was significantly lower than occipital IMP uptake (p < 0.01), but there
      was no difference between parietal and occipital FDG uptake. CONCLUSIONS: Our
      findings suggest that parietal metabolism and perfusion are severely affected in
      DLB patients, though the occipital metabolic and perfusional reduction is thought
      to be a feature of DLB. FDG-PET is thought to be superior to IMP-SPECT in
      detecting functional changes in the DLB brain.

PMID- 15462409
TI  - Mapping QTLs for traits measured as percentages.
AB  - Many quantitative traits are measured as percentages. As a result, the assumption
      of a normal distribution for the residual errors of such percentage data is often
      violated. However, most quantitative trait locus (QTL) mapping procedures assume
      normality of the residuals. Therefore, proper data transformation is often
      recommended before statistical analysis is conducted. We propose the probit
      transformation to convert percentage data into variables with a normal
      distribution. The advantage of the probit transformation is that it can handle
      measurement errors with heterogeneous variance and correlation structure in a
      statistically sound manner. We compared the results of this data transformation
      with other transformations and found that this method can substantially increase
      the statistical power of QTL detection. We develop the QTL mapping procedure
      based on the maximum likelihood methodology implemented via the expectation
      maximization algorithm. The efficacy of the new method is demonstrated using
      Monte Carlo simulation.

PMID- 15462410
TI  - Sex-specific selection on the human X chromosome?
AB  - Genes involved in major biological functions, such as reproductive or cognitive
      functions, are choice targets for natural selection. However, the extent to which
      these genes are affected by selective pressures remains undefined. The apparent
      clustering of these genes on sex chromosomes makes this genomic region an
      attractive model system to study the effects of evolutionary forces. In the
      present study, we analysed the genetic diversity of a X-linked microsatellite in
      1410 X-chromosomes from 10 different human populations. Allelic frequency
      distributions revealed an unexpected discrepancy between the sexes. By evaluating
      the different scenarios that could have led to this pattern, we show that sex
      specific selection on the tightly linked VCX gene could be the most likely cause
      of such a distortion.

PMID- 15462411
TI  - Use of regression methods to identify motifs that modulate germline transcription
      in Drosophila melanogaster.
AB  - Identification of cis-regulatory motifs has been difficult due to the short and
      variable length of the sequences that bind transcription factors. Using both
      sequence and microarray expression data, we present a method for identifying cis
      regulatory motifs that uses regression trees to refine results from simple linear
      regression of expression levels on motif counts. Analysis of expression patterns
      from two separate datasets for genes showing significant differences in
      expression between the sexes in Drosophila melanogaster resulted in a model that
      identified known binding sites upstream of genes that are differentially
      expressed in the germline. We obtained a strong result for motif TCGATA, part of
      the larger, characterized binding site of dGATAb protein. We also identified an
      uncharacterized motif that is positively associated with sex-biased expression
      and was assembled from smaller motifs grouped by our model. A regression tree
      model provides a grouping of independent variables into multiple linear models,
      an advantage over a single multivariate model. In our case, this grouping of
      motifs suggests binding sites for cooperating factors in sex-specific expression,
      as well as a way of combining smaller motifs into larger binding sites.

PMID- 15462412
TI  - Insecticide resistance genes confer a predation cost on mosquitoes, Culex
      pipiens.
AB  - Newly occurring adaptive genes, such as those providing insecticide resistance,
      display a fitness cost which is poorly understood. In order to detect subtle
      behavioural changes induced by the presence of resistance genes, we used natural
      predators and compared their differential predation on susceptible and resistant
      Culex pipiens mosquitoes, using strains with a similar genetic background.
      Resistance genes were either coding an overproduced detoxifying esterase (locus
      Ester), or an insensitive target (locus ace-1). Differential predation was
      measured between susceptible and resistant individuals, as well as among
      resistant mosquitoes. A backswimmer, a water measurer, a water boatman and a
      predaceous diving beetle were used as larval predators, and a pholcid spider as
      adult predator. Overall, the presence of a resistance gene increased the
      probability of predation: all resistance genes displayed predation costs relative
      to susceptible ones, at either the larval or adult stage, or both. Interestingly,
      predation preferences among the susceptible and the resistance genes were not
      ranked uniformly. Possible explanations for these results are given, and we
      suggest that predators, which are designed by natural selection to detect
      specific behavioural phenotypes, are useful tools to explore non-obvious
      differences between two classes of individuals, for example when they differ by
      the presence or absence of one recent gene, such as insecticide resistance genes.

PMID- 15462413
TI  - Simultaneous mapping of epistatic QTL in chickens reveals clusters of QTL pairs
      with similar genetic effects on growth.
AB  - We used simultaneous mapping of interacting quantitative trait locus (QTL) pairs
      to study various growth traits in a chicken F2 intercross. The method was shown
      to increase the number of detected QTLs by 30 % compared with a traditional
      method detecting QTLs by their marginal genetic effects. Epistasis was shown to
      be an important contributor to the genetic variance of growth, with the largest
      impact on early growth (before 6 weeks of age). There is also evidence for a
      discrete set of interacting loci involved in early growth, supporting the
      previous findings of different genetic regulation of early and late growth in
      chicken. The genotype-phenotype relationship was evaluated for all interacting
      QTL pairs and 17 of the 21 evaluated QTL pairs could be assigned to one of four
      clusters in which the pairs in a cluster have very similar genetic effects on
      growth. The genetic effects of the pairs indicate commonly occurring dominance-by
      dominance, heterosis and multiplicative interactions. The results from this study
      clearly illustrate the increase in power obtained by using this novel method for
      simultaneous detection of epistatic QTL, and also how visualization of genotype
      phenotype relationships for epistatic QTL pairs provides new insights to
      biological mechanisms underlying complex traits.

PMID- 15462414
TI  - Segregation of QTL for production traits in commercial meat-type chickens.
AB  - This study investigated whether quantitative trait loci (QTL) identified in
      experimental crosses of chickens provide a short cut to the identification of QTL
      in commercial populations. A commercial population of broilers was targeted for
      chromosomal regions in which QTL for traits associated with meat production have
      previously been detected in extreme crosses. A three-generation design,
      consisting of 15 grandsires, 608 half-sib hens and over 15 000 third-generation
      offspring, was implemented within the existing breeding scheme of a broiler
      breeding company. The first two generations were typed for 52 microsatellite
      markers spanning regions of nine chicken chromosomes and covering a total of 730
      cM, approximately one-fifth of the chicken genome. Using half-sib analyses with a
      multiple QTL model, linkage was studied between these regions and 17 growth and
      carcass traits. Out of 153 trait x region comparisons, 53 QTL exceeded the
      threshold for genome-wide significance while an additional 23 QTL were
      significant at the nominal 1% level. Many of the QTL affect the carcass
      proportions and feed intake, for which there are few published studies. Given
      intensive selection for efficient growth in broilers for more than 50 generations
      it is surprising that many QTL affecting these traits are still segregating.
      Future fine-mapping efforts could elucidate whether ancestral mutations are still
      segregating as a result of pleiotropic effects on fitness traits or whether this
      variation is due to new mutations.

PMID- 15462415
TI  - The clinical potential of intensity modulated proton therapy.
AB  - Intensity Modulated Proton Therapy (IMPT) differs from conventional proton
      therapy in its ability to deliver depth-shifted, arbitrarily complex proton
      fluence maps from each incident field direction. As the individual Bragg peaks
      delivered from any field can be distributed in three-dimensions throughout the
      target volume, IMPT provides many more degrees of freedom for designing dose
      distributions than IMRT or conventional proton therapy techniques. So how can the
      flexibility of IMPT best be exploited? Here we argue that IMPT has two main
      advantages over photon IMRT and conventional proton therapy: the ability to
      better 'sculpt' the dose to the target and around neighbouring critical
      structures, and the ability to find clinically acceptable solutions whilst
      simultaneously reducing the sensitivity of the treatments to potential delivery
      errors. The concept of IMPT as a tool for generating 'safer' plans opens an
      interesting new avenue of research from the point of view of plan optimisation,
      the potential of which is only just beginning to be explored.

PMID- 15462416
TI  - [Dependence of uniformity on the radionuclide in SPECT: test methods].
AB  - The aim of this study was to investigate test methods to clarify whether the non
      uniformity of a gamma camera depends on individual radionuclides, and whether it
      is necessary to measure a separate correction matrix for each radionuclide used
      in single photon emission computed tomography (SPECT). Two methods were devised
      to verify the nuclide-dependence of the gamma camera. In order to test the energy
      correction of the detectors, the first approach was based on the evaluation of
      the intrinsic non-uniformity and on the production of images with asymmetrical
      energy window. The second method was based on the production of correction
      matrices for different radionuclides, as well as on the subsequent application to
      phantom data that were also generated with different radionuclides. The
      investigation of a dualhead gamma camera produced the same results with both
      methods. One detector head was found to be weakly dependent on the radionuclide,
      due to the insufficient quality of energy correction. In this case, the phantom
      or patient data should be corrected using a uniformity correction matrix measured
      with the same radionuclide. The second detector remained nuclide-independent; in
      this case the uniformity correction matrix acquired for only one radionuclide was
      sufficient.

PMID- 15462417
TI  - Basic treatment planning parameters for a 90Sr / 90Y source train used in
      endovascular brachytherapy.
AB  - Working groups of the AAPM, DGMP, and ESTRO have published recommendations for
      endovascular brachytherapy, introducing concepts of relevant parameters for dose
      specification and treatment planning. However, the procedures for this treatment
      remain often mainly based on trial protocols and manufacturer instructions.
      Treatment planning requires the essential knowledge of the radial and
      longitudinal dose distribution, as well as information about geometrical
      uncertainties. The present study includes a whole data set for daily clinical
      practice using a commercially available device for endovascular brachytherapy
      (Novoste Betacath). The dose distribution around the 90Sr seed train was
      calculated with Monte-Carlo algorithms and verified by film dosimetry. The radial
      dose profile was determined starting from the surface of the delivery catheter
      Calculated dose profiles were in good agreement to measured values. The
      geometrical uncertainties were estimated with a retrospective analysis of 51
      patient treatments. This shows the importance of using a safety margin of at
      least 10 mm between Intervention Length and Reference Isodose Length. Based on
      the longitudinal dose profile and the necessary safety margins, the maximum
      treatable intervention length is 25 mm and 45 mm for a 40 mm and 60 mm source
      train, respectively.

PMID- 15462418
TI  - Fetal dose reduction in head and neck radiotherapy of a pregnant woman.
AB  - BACKGROUND AND PURPOSE: A pregnant woman was referred for post-operative
      radiotherapy of a malignant schwannoma in the head and neck region. A best
      treatment plan was devised in order to minimize the fetal dose. MATERIAL AND
      METHODS: The fetal dose resulting from radiological examinations was determined
      according to international protocols, that resulting from radiotherapy was
      calculated according to Recommendation 36 of the American Association of
      Physicists in Medicine (AAPM) Task Group. Pre-treatment dosimetry was performed
      with an anthropomorphic phantom. Several alternative treatment plans were
      evaluated. The use of a multileaf collimator (MLC) and a virtual wedge (VW) was
      compared to cerrobend blocks (CB) and physical wedge (PW). In-vivo dosimetry was
      performed using a vaginal probe containing thermoluminescent dosimeters (TLD).
      RESULTS: The total fetal dose resulting from diagnostic and radiotherapy
      procedures was estimated to be 36 mGy. The technique based on MLC and VW was
      elected for patient treatment. Measurements for this configuration resulted in
      afetal dose reduction of 82%. The shielding of the patient's abdomen further
      reduced the fetal dose by 42%. CONCLUSION: The use of VW and MLC for the
      treatment of a pregnant woman is highly recommended. Each case should be
      individually studied with pre-treatment and in-vivo dosimetry.

PMID- 15462419
TI  - [Spatial and temporal control of ultrasonic fields via optoacoustic holography].
AB  - The present paper presents a new method for generating ultrasound, based on the
      interaction of laser-induced ultrasound generation and ultrasonic holography. An
      ultrasonic field generated in a water tank via the optoacoustic effect is
      spatially and temporally controlled: In order to produce defined ultrasonic
      frequencies in the MHz range, the laser pulses incident on a light-absorbing
      layer are modulated in time using an electro-optic modulator (EOM). Additionally,
      a high-resolution liquid crystal spatial light modulator (SLM) is used to imprint
      a pre-calculated phase front to the laser beam. A computer-generated binary
      hologram is also displayed at the SLM. The expanded laser beam projects the
      corresponding pattern to the plane absorptive layer in the water tank. The
      projection of specific patterns for the generation of ultrasonic beams resembles
      the use of, diffractive optical elements" in optics. Optical ultrasound
      generation with holographic steering is a flexible tool with promising numerous
      new applications in medical and technical ultrasound diagnostics.

PMID- 15462420
TI  - The simultaneous integrated boost with proton beams in head and neck patients.
AB  - The potential benefit of the simultaneous integrated boost (SIB) concept in
      proton therapy was investigated in a planning study. The proposed fractionation
      strategy consisted of a SIB treatment following a first phase of conventional
      fractionation to the elective volume (named SEQ/SIB). The novel method was
      compared to a conventional sequential fractionation and to a full SIB approach.
      Treatment plans were designed for five patients on the proton planning system
      developed for spot scanning at the Paul Scherrer Institute of Villigen (CH).
      Three to five beams were applied for all plans and fractionations. All effective
      dose distributions were corrected using biological models to take into account
      repopulation and time at repopulation onset. Corrected and uncorrected plans were
      compared on the basis of dosimetry criteria and dose-volume histograms. The
      results showed a dosimetric advantage for the SEQ/SIB approach in terms of target
      coverage, without significant disadvantages for risk structures and healthy
      tissue. Considering the high logistic impact and the limited availability of
      radiation facilities, the clinical exploitation of accelerated SIB treatment with
      protons appears promising.

PMID- 15462421
TI  - Combining magnetic and optical tracking for computer aided therapy.
AB  - A fast and accurate magnetic tracking system was developed for applications in
      real-time tumor tracking, computer-aided surgery, and endoscopy. The tracking is
      based on the application of miniaturized sensors. Once implanted in the patient,
      the sensors receive signals from an external field generator. The fast evaluation
      of the signals allows the online determination of position and orientation of
      each sensor. With the help of optical tracking, the sensor coordinates are
      transformed in the reference system used by the clinician. The effects of eddy
      currents in nearby electrically-conducting objects are taken into account using
      special computational methods. The present paper presents the results of a first
      experiment in a canine model.

PMID- 15462422
TI  - External targets for the production of 211At--review and status of the target
      development at the Hannover cyclotron.
AB  - 211At is an alpha emitter which can be produced with cyclotrons capable of
      accelerating helium-4 ions to at least 28 MeV in case of external targets.
      Different targets were used and improved to increase the yield of 211At to
      amounts considered to be suitable for alpha therapy of tumours.

PMID- 15462423
TI  - Comments to the forum of M. Goitein.

PMID- 15462424
TI  - Vacancy, turnover rates stable in face of staffing challenges.

PMID- 15462425
TI  - Clinical ladders ramp up staff's enthusiasm and participation.

PMID- 15462426
TI  - JCAHO issues 2005 Patient Safety Goals.

PMID- 15462427
TI  - Fewer staffing challenges for ASCs.

PMID- 15462428
TI  - "Hardy nurses" less likely to burn out.

PMID- 15462429
TI  - "Smart" wristbands tested for patient ID.

PMID- 15462430
TI  - What to know about ASC benchmarking.

PMID- 15462431
TI  - Adaptive neural network control for a class of MIMO nonlinear systems with
      disturbances in discrete-time.
AB  - In this paper, adaptive neural network (NN) control is investigated for a class
      of multiinput and multioutput (MIMO) nonlinear systems with unknown bounded
      disturbances in discrete-time domain. The MIMO system under study consists of
      several subsystems with each subsystem in strict feedback form. The inputs of the
      MIMO system are in triangular form. First, through a coordinate transformation,
      the MIMO system is transformed into a sequential decrease cascade form (SDCF).
      Then, by using high-order neural networks (HONN) as emulators of the desired
      controls, an effective neural network control scheme with adaptation laws is
      developed. Through embedded backstepping, stability of the closed-loop system is
      proved based on Lyapunov synthesis. The output tracking errors are guaranteed to
      converge to a residue whose size is adjustable. Simulation results show the
      effectiveness of the proposed control scheme.

PMID- 15462432
TI  - On combining support vector machines and simulated annealing in stereovision
      matching.
AB  - This paper outlines a method for solving the stereovision matching problem using
      edge segments as the primitives. In stereovision matching, the following
      constraints are commonly used: epipolar, similarity, smoothness, ordering, and
      uniqueness. We propose a new strategy in which such constraints are sequentially
      combined. The goal is to achieve high performance in terms of correct matches by
      combining several strategies. The contributions of this paper are reflected in
      the development of a similarity measure through a support vector machines
      classification approach; the transformation of the smoothness, ordering and
      epipolar constraints into the form of an energy function, through an optimization
      simulated annealing approach, whose minimum value corresponds to a good matching
      solution and by introducing specific conditions to overcome the violation of the
      smoothness and ordering constraints. The performance of the proposed method is
      illustrated by comparative analysis against some recent global matching methods.

PMID- 15462433
TI  - Inference of reversible tree languages.
AB  - In this paper, we study the notion of k-reversibility and k-testability when
      regular tree languages are involved. We present an inference algorithm for
      learning a k-testable tree language that runs in polynomial time with respect to
      the size of the sample used. We also study the tree language classes in relation
      to other well known ones, and some properties of these languages are proven.

PMID- 15462434
TI  - Face recognition using fuzzy integral and wavelet decomposition method.
AB  - In this paper, we develop a method for recognizing face images by combining
      wavelet decomposition, Fisherface method, and fuzzy integral. The proposed
      approach is comprised of four main stages. The first stage uses the wavelet
      decomposition that helps extract intrinsic features of face images. As a result
      of this decomposition, we obtain four subimages (namely approximation,
      horizontal, vertical, and diagonal detailed images). The second stage of the
      approach concerns the application of the Fisherface method to these four
      decompositions. The choice of the Fisherface method in this setting is motivated
      by its insensitivity to large variation in light direction, face pose, and facial
      expression. The two last phases are concerned with the aggregation of the
      individual classifiers by means of the fuzzy integral. Both Sugeno and Choquet
      type of fuzzy integral are considered as the aggregation method. In the
      experiments we use n-fold cross-validation to assure high consistency of the
      produced classification outcomes. The experimental results obtained for the
      Chungbuk National University (CNU) and Yale University face databases reveal that
      the approach presented in this paper yields better classification performance in
      comparison to the results obtained by other classifiers.

PMID- 15462435
TI  - Multioriented and curved text lines extraction from Indian documents.
AB  - There are printed artistic documents where text lines of a single page may not be
      parallel to each other. These text lines may have different orientations or the
      text lines may be curved shapes. For the optical character recognition (OCR) of
      these documents, we need to extract such lines properly. In this paper, we
      propose a novel scheme, mainly based on the concept of water reservoir analogy,
      to extract individual text lines from printed Indian documents containing
      multioriented and/or curve text lines. A reservoir is a metaphor to illustrate
      the cavity region of a character where water can be stored. In the proposed
      scheme, at first, connected components are labeled and identified either as
      isolated or touching. Next, each touching component is classified either straight
      type (S-type) or curve type (C-type), depending on the reservoir base-area and
      envelope points of the component. Based on the type (S-type or C-type) of a
      component two candidate points are computed from each touching component.
      Finally, candidate regions (neighborhoods of the candidate points) of the
      candidate points of each component are detected and after analyzing these
      candidate regions, components are grouped to get individual text lines.

PMID- 15462437
TI  - Using distributed partial memories to improve self-organizing collective
      movements.
AB  - Past self-organizing models of collectively moving "particles" (simulated bird
      flocks, fish schools, etc.) have typically been based on purely reflexive agents
      that have no significant memory of past movements. We hypothesized that giving
      such individual particles a limited distributed memory of past obstacles they
      encountered could lead to significantly faster travel between goal destinations.
      Systematic computational experiments using six terrains that had different
      arrangements of obstacles demonstrated that, at least in some domains, this
      conjecture is true. Furthermore, these experiments demonstrated that improved
      performance over time came not only from the avoidance of previously seen
      obstacles, but also (surprisingly) immediately after first encountering obstacles
      due to decreased delays in circumventing those obstacles. Simulations also showed
      that, of the four strategies we tested for removal of remembered obstacles when
      memory was full and a new obstacle was to be saved, none was better than random
      selection. These results may be useful in interpreting future experimental
      research on group movements in biological populations, and in improving existing
      methodologies for control of collective movements in computer graphics, robotic
      teams, particle swarm optimization, and computer games.

PMID- 15462436
TI  - Generating high-speed dynamic running gaits in a quadruped robot using an
      evolutionary search.
AB  - Over the past several decades, there has been a considerable interest in
      investigating high-speed dynamic gaits for legged robots. While much research has
      been published, both in the biomechanics and engineering fields regarding the
      analysis of these gaits, no single study has adequately characterized the
      dynamics of high-speed running as can be achieved in a realistic, yet simple,
      robotic system. The goal of this paper is to find the most energy-efficient,
      natural, and unconstrained gallop that can be achieved using a simulated
      quadrupedal robot with articulated legs, asymmetric mass distribution, and
      compliant legs. For comparison purposes, we also implement the bound and canter.
      The model used here is planar, although we will show that it captures much of the
      predominant dynamic characteristics observed in animals. While it is not our goal
      to prove anything about biological locomotion, the dynamic similarities between
      the gaits we produce and those found in animals does indicate a similar
      underlying dynamic mechanism. Thus, we will show that achieving natural,
      efficient high-speed locomotion is possible even with a fairly simple robotic
      system. To generate the high-speed gaits, we use an efficient evolutionary
      algorithm called set-based stochastic optimization. This algorithm finds open
      loop control parameters to generate periodic trajectories for the body. Several
      alternative methods are tested to generate periodic trajectories for the legs.
      The combined solutions found by the evolutionary search and the periodic-leg
      methods, over a range of speeds up to 10.0 m/s, reveal "biological"
      characteristics that are emergent properties of the underlying gaits.

PMID- 15462438
TI  - Sparse kernel density construction using orthogonal forward regression with leave
      one-out test score and local regularization.
AB  - This paper presents an efficient construction algorithm for obtaining sparse
      kernel density estimates based on a regression approach that directly optimizes
      model generalization capability. Computational efficiency of the density
      construction is ensured using an orthogonal forward regression, and the algorithm
      incrementally minimizes the leave-one-out test score. A local regularization
      method is incorporated naturally into the density construction process to further
      enforce sparsity. An additional advantage of the proposed algorithm is that it is
      fully automatic and the user is not required to specify any criterion to
      terminate the density construction procedure. This is in contrast to an existing
      state-of-art kernel density estimation method using the support vector machine
      (SVM), where the user is required to specify some critical algorithm parameter.
      Several examples are included to demonstrate the ability of the proposed
      algorithm to effectively construct a very sparse kernel density estimate with
      comparable accuracy to that of the full sample optimized Parzen window density
      estimate. Our experimental results also demonstrate that the proposed algorithm
      compares favorably with the SVM method, in terms of both test accuracy and
      sparsity, for constructing kernel density estimates.

PMID- 15462439
TI  - An evolutionary algorithm for large traveling salesman problems.
AB  - This work proposes an evolutionary algorithm, called the heterogeneous selection
      evolutionary algorithm (HeSEA), for solving large traveling salesman problems
      (TSP). The strengths and limitations of numerous well-known genetic operators are
      first analyzed, along with local search methods for TSPs from their solution
      qualities and mechanisms for preserving and adding edges. Based on this analysis,
      a new approach, HeSEA is proposed which integrates edge assembly crossover (EAX)
      and Lin-Kernighan (LK) local search, through family competition and heterogeneous
      pairing selection. This study demonstrates experimentally that EAX and LK can
      compensate for each other's disadvantages. Family competition and heterogeneous
      pairing selections are used to maintain the diversity of the population, which is
      especially useful for evolutionary algorithms in solving large TSPs. The proposed
      method was evaluated on 16 well-known TSPs in which the numbers of cities range
      from 318 to 13509. Experimental results indicate that HeSEA performs well and is
      very competitive with other approaches. The proposed method can determine the
      optimum path when the number of cities is under 10,000 and the mean solution
      quality is within 0.0074% above the optimum for each test problem. These findings
      imply that the proposed method can find tours robustly with a fixed small
      population and a limited family competition length in reasonable time, when used
      to solve large TSPs.

PMID- 15462440
TI  - A controlled genetic programming approach for the deceptive domain.
AB  - Traditional genetic programming (GP) randomly combines subtrees by applying
      crossover. There is a growing interest in methods that can control such
      recombination operations in order to achieve faster convergence. In this paper, a
      new approach is presented for guiding the recombination process for genetic
      programming. The method is based on extracting the global information of the
      promising solutions that appear during the genetic search. The aim is to use this
      information to control the crossover operation afterwards. A separate control
      module is used to process the collected information. This module guides the
      search process by sending feedback to the genetic engine about the consequences
      of possible recombination alternatives.

PMID- 15462441
TI  - Reliable LQ fuzzy control for continuous-time nonlinear systems with actuator
      faults.
AB  - This paper deals with the reliable linear quadratic (LQ) fuzzy control problem
      for continuous-time nonlinear systems with actuator faults. The Takagi-Sugeno (T
      S) fuzzy model is employed to represent a nonlinear system. By using multiple
      Lyapunov functions, an improved linear matrix inequality (LMI) method for the
      design of reliable LQ fuzzy controllers is investigated, which reduces the
      conservatism of using a single Lyapunov function. The different upper bounds on
      the LQ performance cost function for the normal and different actuator fault
      cases are provided. A suboptimal reliable LQ fuzzy controller is given by means
      of an LMI optimization procedure, which can not only guarantee the stability of
      the closed-loop overall fuzzy system for all cases, but also provide an optimized
      upper bound on a weighted average LQ performance cost function. Finally,
      numerical simulations on the chaotic Lorenz system are given to illustrate the
      application of the proposed design method.

PMID- 15462442
TI  - Recognizing plankton images from the shadow image particle profiling evaluation
      recorder.
AB  - We present a system to recognize underwater plankton images from the shadow image
      particle profiling evaluation recorder (SIPPER). The challenge of the SIPPER
      image set is that many images do not have clear contours. To address that, shape
      features that do not heavily depend on contour information were developed. A soft
      margin support vector machine (SVM) was used as the classifier. We developed a
      way to assign probability after multiclass SVM classification. Our approach
      achieved approximately 90% accuracy on a collection of plankton images. On
      another larger image set containing manually unidentifiable particles, it also
      provided 75.6% overall accuracy. The proposed approach was statistically
      significantly more accurate on the two data sets than a C4.5 decision tree and a
      cascade correlation neural network. The single SVM significantly outperformed
      ensembles of decision trees created by bagging and random forests on the smaller
      data set and was slightly better on the other data set. The 15-feature subset
      produced by our feature selection approach provided slightly better accuracy than
      using all 29 features. Our probability model gave us a reasonable rejection curve
      on the larger data set.

PMID- 15462443
TI  - Phase-based dual-microphone robust speech enhancement.
AB  - A dual-microphone speech-signal enhancement algorithm, utilizing phase-error
      based filters that depend only on the phase of the signals, is proposed. This
      algorithm involves obtaining time-varying, or alternatively, time-frequency (TF),
      phase-error filters based on prior knowledge regarding the time difference of
      arrival (TDOA) of the speech source of interest and the phases of the signals
      recorded by the microphones. It is shown that by masking the TF representation of
      the speech signals, the noise components are distorted beyond recognition while
      the speech source of interest maintains its perceptual quality. This is supported
      by digit recognition experiments which show a substantial recognition accuracy
      rate improvement over prior multimicrophone speech enhancement algorithms. For
      example, for a case with two speakers with a 0.1 s reverberation time, the phase
      error based technique results in a 28.9% recognition rate gain over the single
      channel noisy signal, a gain of 22.0% over superdirective beamforming, and a gain
      of 8.5% over postfiltering.

PMID- 15462444
TI  - Fuzzy utility and equilibria.
AB  - A decision maker is frequently confronted with fuzzy constraints, fuzzy utility
      maximization, and fuzziness about the state of competitors. In this paper we
      present a framework for fuzzy decision-making, using techniques from fuzzy logic,
      game theory, and micro-economics. In the first part, we study the rationality of
      fuzzy choice. We introduce fuzzy constraints, and show that this can easily be
      combined with maximizing a fuzzy utility. The second part of the paper analyzes
      games with uncertainty about the state of the competitors. We implement fuzzy
      Cournot adjustment, define equilibria, and study their stability. Finally, we
      show how a play progresses where the players have uncertainty about the state of
      the other players, and about their utility. For a likely procedure of utility
      maximization, the equilibria are the same as for the game without utility
      maximization.

PMID- 15462445
TI  - A hybrid fuzzy logic/constraint satisfaction problem approach to automatic
      decision making in simulation game models.
AB  - Possible techniques for representing automatic decision-making behavior
      approximating human experts in complex simulation model experiments are of
      interest. Here, fuzzy logic (FL) and constraint satisfaction problem (CSP)
      methods are applied in a hybrid design of automatic decision making in simulation
      game models. The decision processes of a military headquarters are used as a
      model for the FL/CSP decision agents choice of variables and rulebases. The
      hybrid decision agent design is applied in two different types of simulation
      games to test the general applicability of the design. The first application is a
      two-sided zero-sum sequential resource allocation game with imperfect information
      interpreted as an air campaign game. The second example is a network flow
      stochastic board game designed to capture important aspects of land manoeuvre
      operations. The proposed design is shown to perform well also in this complex
      game with a very large (billionsize) action set. Training of the automatic FL/CSP
      decision agents against selected performance measures is also shown and results
      are presented together with directions for future research.

PMID- 15462446
TI  - Development of a biomimetic robotic fish and its control algorithm.
AB  - This paper is concerned with the design of a robotic fish and its motion control
      algorithms. A radio-controlled, four-link biomimetic robotic fish is developed
      using a flexible posterior body and an oscillating foil as a propeller. The
      swimming speed of the robotic fish is adjusted by modulating joint's oscillating
      frequency, and its orientation is tuned by different joint's deflections. Since
      the motion control of a robotic fish involves both hydrodynamics of the fluid
      environment and dynamics of the robot, it is very difficult to establish a
      precise mathematical model employing purely analytical methods. Therefore, the
      fish's motion control task is decomposed into two control systems. The online
      speed control implements a hybrid control strategy and a proportional-integral
      derivative (PID) control algorithm. The orientation control system is based on a
      fuzzy logic controller. In our experiments, a point-to-point (PTP) control
      algorithm is implemented and an overhead vision system is adopted to provide real
      time visual feedback. The experimental results confirm the effectiveness of the
      proposed algorithms.

PMID- 15462447
TI  - Online monitoring by dynamically refining imprecise models.
AB  - Model-based monitoring determines faults in a supervised system by comparing the
      available system's measurements with a priori information represented by the
      system's mathematical model. Especially in technical environments, a monitoring
      system must be able to reason with incomplete knowledge about the supervised
      system, to process noisy and erroneous observations and to react within a limited
      time. We present MOSES, a model-based monitoring system which is based on
      imprecise models where the structure is known and the parameters may be
      imprecisely specified by numerical intervals. As a consequence, only bounds on
      the trajectories can be derived with imprecise models. These bounds are computed
      using traditional numerical integration techniques starting from individual
      points on the external surface of the model's uncertainty space. When new
      measurements from the supervised system become available, MOSES checks the
      consistency of this new information with the model's prediction and refutes
      inconsistent parts from the uncertainty space of the model. A fault in the
      supervised system is detected when the complete model's uncertainty space has
      been refuted. MOSES bridges and extends methodologies from the FDI and DX
      communities by refining the model's uncertainty space conservatively through
      refutation, by applying standard numerical techniques for deriving the
      trajectories of imprecise models and by exploiting the measurements as soon as
      possible for online monitoring. The performance of MOSES is evaluated based on
      examples and by online monitoring a complex heating system.

PMID- 15462448
TI  - An adaptive, self-organizing dynamical system for hierarchical control of bio
      inspired locomotion.
AB  - In this paper, dynamical systems made up of locally coupled nonlinear units are
      used to control the locomotion of bio-inspired robots and, in particular, a
      simulation of an insect-like hexapod robot. These controllers are inspired by the
      biological paradigm of central pattern generators and are responsible for
      generating a locomotion gait. A general structure, which is able to change the
      locomotion gait according to environmental conditions, is introduced. This
      structure is based on an adaptive system, implemented by motor maps, and is able
      to learn the correct locomotion gait on the basis of a reward function. The
      proposed control system is validated by a large number of simulations carried out
      in a dynamic environment for simulating legged robots.

PMID- 15462449
TI  - Fast and reliable active appearance model search for 3-D face tracking.
AB  - This paper addresses the three-dimensional (3-D) tracking of pose and animation
      of the human face in monocular image sequences using active appearance models.
      The major problem of the classical appearance-based adaptation is the high
      computational time resulting from the inclusion of a synthesis step in the
      iterative optimization. Whenever the dimension of the face space is large, a real
      time performance cannot be achieved. In this paper, we aim at designing a fast
      and stable active appearance model search for 3-D face tracking. The main
      contribution is a search algorithm whose CPU-time is not dependent on the
      dimension of the face space. Using this algorithm, we show that both the CPU-time
      and the likelihood of a nonaccurate tracking are reduced. Experiments evaluating
      the effectiveness of the proposed algorithm are reported, as well as method
      comparison and tracking synthetic and real image sequences.

PMID- 15462450
TI  - Fuzzy dynamic output feedback control with adaptive rotor imbalance compensation
      for magnetic bearing systems.
AB  - This paper presents a dynamic output feedback control with adaptive rotor
      imbalance compensation based on an analytical Takagi-Sugeno fuzzy model for
      complex nonlinear magnetic bearing systems with rotor eccentricity. The rotor
      mass-imbalance effect is considered with a linear in the parameter approximator.
      Through the robust analysis for disturbance rejection, the control law can be
      synthesized in terms of linear matrix inequalities. Based on the suggested fuzzy
      output feedback design, the controller may be much easier to implement than
      conventional nonlinear controllers. Simulation validations show that the proposed
      robust fuzzy control law can suppress the rotor imbalance-induced vibration and
      has excellent capability for high-speed tracking and levitation control.

PMID- 15462451
TI  - Hybrid compensation control for affine TSK fuzzy control systems.
AB  - The paper proposes a way of designing state feedback controllers for affine
      Takagi-Sugeno-Kang (TSK) fuzzy models. In the approach, by combining two
      different control design methodologies, the proposed controller is designed to
      compensate all rules so that the desired control performance can appear in the
      overall system. Our approach treats all fuzzy rules as variations of a nominal
      rule and such variations are individually dealt with in a Lyapunov sense.
      Previous approaches have proposed a similar idea but the variations are dealt
      with as a whole in a robust control sense. As a consequence, when fuzzy rules are
      distributed in a wide range, the stability conditions may not be satisfied. In
      addition, the control performance of the closed-loop system cannot be anticipated
      in those approaches. Various examples were conducted in our study to demonstrate
      the effectiveness of the proposed control design approach. All results illustrate
      good control performances as desired.

PMID- 15462452
TI  - An intelligent service-based network architecture for wearable robots.
AB  - We are developing a novel robot concept called the wearable robot. Wearable
      robots are mobile information devices capable of supporting remote communication
      and intelligent interaction between networked entities. In this paper, we explore
      the possible functions of such a robotic network and will present a distributed
      network architecture based on service components. In order to support the
      interaction and communication between the components in the wearable robot
      system, we have developed an intelligent network architecture. This service-based
      architecture involves three major mechanisms. The first mechanism involves the
      use of a task coordinator service such that the execution of the services can be
      managed using a priority queue. The second mechanism enables the system to
      automatically push the required service proxy to the client intelligently based
      on certain system-related conditions. In the third mechanism, we allow the system
      to automatically deliver services based on contextual information. Using a fuzzy
      logic-based decision making system, the matching service can determine whether
      the service should be automatically delivered utilizing the information provided
      by the service, client, lookup service, and context sensors. An application
      scenario has been implemented to demonstrate the feasibility of this distributed
      service-based robot architecture. The architecture is implemented as extensions
      to the Jini network model.

PMID- 15462453
TI  - Multisensor optimal information fusion input white noise deconvolution
      estimators.
AB  - The unified multisensor optimal information fusion criterion weighted by matrices
      is rederived in the linear minimum variance sense, where the assumption of normal
      distribution is avoided. Based on this fusion criterion, the optimal information
      fusion input white noise deconvolution estimators are presented for discrete time
      varying linear stochastic control system with multiple sensors and correlated
      noises, which can be applied to seismic data processing in oil exploration. A
      three-layer fusion structure with fault tolerant property and reliability is
      given. The first fusion layer and the second fusion layer both have netted
      parallel structures to determine the first-step prediction error cross-covariance
      for the state and the estimation error cross-covariance for the input white noise
      between any two sensors at each time step, respectively. The third fusion layer
      is the fusion center to determine the optimal matrix weights and obtain the
      optimal fusion input white noise estimators. The simulation results for Bernoulli
      Gaussian input white noise deconvolution estimators show the effectiveness.

PMID- 15462454
TI  - Evolutionary design of a fuzzy classifier from data.
AB  - Genetic algorithms show powerful capabilities for automatically designing fuzzy
      systems from data, but many proposed methods must be subjected to some minimal
      structure assumptions, such as rule base size. In this paper, we also address the
      design of fuzzy systems from data. A new evolutionary approach is proposed for
      deriving a compact fuzzy classification system directly from data without any a
      priori knowledge or assumptions on the distribution of the data. At the beginning
      of the algorithm, the fuzzy classifier is empty with no rules in the rule base
      and no membership functions assigned to fuzzy variables. Then, rules and
      membership functions are automatically created and optimized in an evolutionary
      process. To accomplish this, parameters of the variable input spread inference
      training (VISIT) algorithm are used to code fuzzy systems on the training data
      set. Therefore, we can derive each individual fuzzy system via the VISIT
      algorithm, and then search the best one via genetic operations. To evaluate the
      fuzzy classifier, a fuzzy expert system acts as the fitness function. This fuzzy
      expert system can effectively evaluate the accuracy and compactness at the same
      time. In the application section, we consider four benchmark classification
      problems: the iris data, wine data, Wisconsin breast cancer data, and Pima Indian
      diabetes data. Comparisons of our method with others in the literature show the
      effectiveness of the proposed method.

PMID- 15462455
TI  - Robust image segmentation using FCM with spatial constraints based on new kernel
      induced distance measure.
AB  - Fuzzy c-means clustering (FCM) with spatial constraints (FCM_S) is an effective
      algorithm suitable for image segmentation. Its effectiveness contributes not only
      to the introduction of fuzziness for belongingness of each pixel but also to
      exploitation of spatial contextual information. Although the contextual
      information can raise its insensitivity to noise to some extent, FCM_S still
      lacks enough robustness to noise and outliers and is not suitable for revealing
      non-Euclidean structure of the input data due to the use of Euclidean distance
      (L2 norm). In this paper, to overcome the above problems, we first propose two
      variants, FCM_S1 and FCM_S2, of FCM_S to aim at simplifying its computation and
      then extend them, including FCM_S, to corresponding robust kernelized versions
      KFCM_S, KFCM_S1 and KFCM_S2 by the kernel methods. Our main motives of using the
      kernel methods consist in: inducing a class of robust non-Euclidean distance
      measures for the original data space to derive new objective functions and thus
      clustering the non-Euclidean structures in data; enhancing robustness of the
      original clustering algorithms to noise and outliers, and still retaining
      computational simplicity. The experiments on the artificial and real-world
      datasets show that our proposed algorithms, especially with spatial constraints,
      are more effective.

PMID- 15462457
TI  - Guaranteed robust stability of the closed-loop systems for digital controller
      implementations via orthogonal hermitian transform.
AB  - In this paper, an approach for robust stability analysis of a digital closed-loop
      system for digital controller implementations subject to finite word length (FWL)
      effects is proposed. Uncertainties caused by the roundoff and computational
      errors subject to FWL effects are expressed in function of mantissa bit number
      when the mode of floating-point arithmetic is used in the process. Then, based on
      the Small Gain Theorem and the Bellman-Grownwall Lemma, a sufficient stability
      criterion for the digital closed-loop system is derived. The eigenvalue
      sensitivity of the closed-loop system is developed in terms of mixed matrix
      2/Frobenius norms. Then, by minimizing this eigenvalue sensitivity and using
      orthogonal Hermitian transform as well, an optimal similarity transformation can
      be obtained. By substituting this optimal transformation into the stability
      criterion, a minimum mantissa bit number used for implementing the stabilizing
      digital controllers can be determined. The main contributions are that this
      approach provides an analytical closed-form solution for obtaining the optimal
      transformation and, in addition to the stability criterion, leads to the
      implementation of the stabilizing controllers with a lower mantissa bit number
      when using this optimal one. Finally, detailed numerical design processes and
      simulation results are used to illustrate the effectiveness of the proposed
      scheme.

PMID- 15462456
TI  - Task-independent robotic uncalibrated hand-eye coordination based on the extended
      state observer.

PMID- 15462458
TI  - Patterns of agent interaction scenarios as use case maps.
AB  - A use case map (UCM) presents, in general, an abstract description of a complex
      system and, as such, is a good candidate for representing scenarios of autonomous
      agents interacting with other autonomous agents. The "gang of four" design
      patterns are intended for object-oriented software development but at least eight
      of the patterns illustrate structure, or architecture, that is appropriate for
      interacting agents, independent of software development. This study presents
      these particular patterns in the form of UCMs to describe abstract scenarios of
      agent interaction. Seven of the patterns attempt to balance the decentralized
      nature of interacting agents with an organized structure that makes for better,
      cleaner interactions. An example performance analysis is provided for one of the
      patterns, illustrating the benefit of an early abstraction of complex agent
      behavior. The original contribution here is a UCM presentation of the causal
      paths in agent behavior as suggested by software design patterns.

PMID- 15462459
TI  - Geriatric depression: a challenge for the 21st century.

PMID- 15462460
TI  - Depression in the elderly: new concepts and therapeutic approaches.
AB  - Depression is one of the leading causes of suffering in the elderly, but it is
      often under-diagnosed and under-treated, partly due to the false belief that
      depression is a common aspect of aging. Depression in the elderly is frequently
      comorbid with medical illnesses, may often be expressed by somatic complaints,
      and may be a risk factor for other diseases such as dementia and coronary artery
      disease. Depression decreases the quality of life and increases disability and
      the risk of mortality, also due to suicide. Although several effective
      antidepressant drugs are available, with a favorable therapeutic index, non
      pharmacological treatments, such as psychotherapy and exercise, should receive
      greater attention, since combination therapy is probably more effective.

PMID- 15462461
TI  - Adult aging and the perceived intensity of emotions in faces and stories.
AB  - BACKGROUND AND AIMS: Experience of emotions changes with age: older adults report
      fewer intense negative emotional experiences, and are less accurate in labelling
      facial expressions of some negative emotions. However, there is little empirical
      evidence as to the effect of age on perception of intensity of emotions. This
      study aims to investigate whether younger and older adults differ in their
      ratings of the intensity of others' emotions as presented in photographs of faces
      and descriptions in text. METHODS: Age effects on intensity ratings of emotions
      (happiness, fear, anger, sadness) from photographs of facial expressions and
      verbal descriptions of emotions in text were investigated in 91 healthy adult
      participants. Relationships of these intensity ratings with measures of cognitive
      ability and current mood were also examined. RESULTS: Older participants
      perceived lower levels of emotional intensity in sad and happy faces. Compared
      with the older group, younger adults perceived neutral faces as showing high
      anger levels. Younger adults also rated protagonists in stories as experiencing
      high levels of fear. Most of the age differences could be statistically explained
      in terms of anxiety, depression, and intelligence test scores. CONCLUSIONS: Older
      adults rate some aspects of emotions portrayed in facial expressions and written
      text as less intense. This may partly reflect better emotional adjustment with
      age, as reflected in lower levels of anxiety and depression.

PMID- 15462462
TI  - Unspecific clinical presentation of bowel ischemia in the very old. Digitalis
      treatment--a reason for higher mortality?
AB  - BACKGROUND AND AIMS: Ischemic bowel disease predominantly affects the elderly
      (>65 years). Early diagnosis and treatment are of vital importance for the
      outcome. The vague symptoms of ischemic bowel disease entail a risk of delayed
      diagnosis, with a subsequent risk of increased mortality. The aims of this
      retrospective study were to identify symptoms and prodromes, to study factors
      associated with mortality in ischemic bowel disease, and to describe the
      influence of age, by comparing patients <80 and > or = 80 years. METHODS: The
      subjects of the study were 135 patients, mean age 77 years, admitted to Malmo
      University Hospital, Sweden, between 1987 and 1996, with a ICD-9 diagnosis of
      acute or chronic splanchnic ischemia. RESULTS: Patients aged 80 years or more
      presented with a significantly higher prevalence of confusion (29% vs 12%),
      hematemesis (57% vs 14%), vomiting (82% vs 65%) and dehydration (58% vs 36%) at
      admission compared with patients aged under 80 years, and presented a higher
      mortality (87% compared with 65%, p=0.003). The prevalence of digitalis treatment
      was 34%, which was high compared with other Swedish cohort studies. Digitalis,
      adjusted for age, congestive heart failure and atrial fibrillation, was
      associated with increased mortality (odds ratio 4.6, 95% CI 1.3-16.1). Prodromal
      signs predicted poor outcome, and were found in one out of 4 patients, without
      any age differences. CONCLUSIONS: Bowel ischemia in the very old is associated
      with a different clinical presentation and a higher mortality compared with
      younger patients. Digitalis treatment seems to be associated with increased
      mortality in ischemic bowel disease. Prodromal signs are prognostically
      unfavorable.

PMID- 15462463
TI  - Is pulse pressure a predictor of cardiovascular complications in a frail elderly
      nursing home population?
AB  - BACKGROUND AND AIMS: Previous studies have focused on systolic blood pressure
      (SBP), diastolic pressure (DBP), and more recently pulse pressure (PP) as risk
      factors for adverse cardiovascular (CV) endpoints in elderly people. However, the
      relation between these pressures and CV complications in the frail nursing home
      population has not been well studied. The aims of this project are to determine
      the value of PP in predicting CV complications in a nursing home population, and
      to compare its predictive value with SBP, DBP, and mean arterial pressure (MAP).
      METHODS: This study is a retrospective 2-year review of the medical charts of 248
      residents of the Hebrew Rehabilitation Center for the Aged, a long-term care
      facility in Boston, MA, USA. During the review process, data were collected about
      past medical history and new onset CV events, in addition to blood pressure and
      medication use. RESULTS: The results showed, with 95% confidence, that within a 2
      year period, the odds ratio for the occurrence of the selected CV outcomes
      (myocardial infarction, congestive heart failure, angina, stroke, renal failure,
      syncope, death) included 1.0 for PP, SBP, DBP, MAP, and changes in these values.
      After adjusting for medication use, pulse pressure was still not an independent
      risk factor for CV complications. CONCLUSIONS: PP, SBP, DBP or MAP cannot serve
      as predictors of CV outcomes in the nursing home population. The presence of
      multiple medical problems in this frail population may have resulted in CV
      morbidity and mortality, independent of blood pressure effects.

PMID- 15462464
TI  - Predictors of quality of life in older people living at home and in institutions.
AB  - BACKGROUND AND AIMS: Health-related quality of life (QOL) is considered to be the
      key goal for health promotion in older people. The aim of this study was to
      describe the correlates of QOL in home-dwelling and institutionalized elderly.
      METHODS: One hundred and fifty-two elderly residents of long-term care homes and
      160 community-dwelling elderly participated in the study. Assessment included
      demographic and social variables, health status, nutritional state, physical and
      cognitive function. Physical activity (PA) was assessed by two PA questionnaires:
      the Seven Day Recall PA Questionnaire and the Stanford Usual Activity
      Questionnaire. QOL was assessed with the Euroqol 5D questionnaire. RESULTS:
      Depression was the most powerful predictor of QOL in both community-dwelling and
      institutionalized elderly. Complaints associated with the musculoskeletal system
      in community-dwelling elders and manifestations of atherosclerosis and
      cardiovascular diseases in institutionalized elders were the most important
      concomitant diseases. Regular participation in PA, preventing obesity and
      maintaining an adequate level of physical and cognitive function, contributed
      more to overall QOL in community-dwellers than in older and frailer
      institutionalized elderly adults. CONCLUSIONS: The relative contribution of
      functional and medical comorbidities, as well as health-promoting behaviors to
      QOL, may be different in community-dwelling and institutionalized elders.
      Physical and cognitive function deficits, overweight/obesity, and lack of regular
      PA are among primary predictors of decreased QOL in home-dwelling elders. In
      institutionalized subjects, these functional/behavioral data seem to be of lesser
      importance, the role of concomitant diseases becoming dominant.

PMID- 15462465
TI  - Allergic contact sensitivity in elderly patients.
AB  - BACKGROUND AND AIMS: Aging has been shown to be correlated with the rate and type
      of contact sensitization, but only a few studies have evaluated patch test
      reactivity in elderly subjects with an adequately large population. METHODS: The
      response patterns to patch testing in 1444 elderly subjects (>65 years) with
      suspected allergic contact dermatitis were studied, and the results compared with
      a control group of individuals with suspected allergic contact dermatitis, aged
      between 20 and 40 years. RESULTS: The prevalence of the positive patch test to at
      least one hapten was significantly lower in the group of elderly patients
      compared with adult patients (40.7 vs 47.8%, p<0.0001). However, some allergens,
      i.e., primin, diaminodiphenylmethane, neomycin, lanolin alcohols, paraben mix,
      Euxyl K400 and quinoline mix, showed an increased sensitization rate in elderly
      patients compared with adult patients. These allergens are now less frequently
      employed in the workplace, or are substances particularly used in the formulation
      of topical treatment of age-related diseases, i.e., leg ulcer and xerosis. It was
      also found that the intensity of positive patch test reactions was significantly
      lower in elderly patients compared with younger subjects, with higher proportions
      of weak (+) positive reactions. Moreover, elderly patients showed a dynamic
      pattern of increasing intensity of patch test reactions at the second reading
      after 3 days compared with the first reading after 2 days more frequently than
      younger patients (60 vs 53%, p<0.0001). CONCLUSIONS: These findings suggest an
      age-dependent decline of overall positive patch test reactions, but a higher
      sensitization rate to some allergens frequently used in the composition of
      topical treatments. The development of an allergic response in elderly patients
      was found to be delayed, and this may require an additional reading after 7 days
      and the interpretation of even weak reactions as valid positive patch test
      reactions.

PMID- 15462466
TI  - Do severity and duration of depressive symptoms predict cognitive decline in
      older persons? Results of the Longitudinal Aging Study Amsterdam.
AB  - BACKGROUND AND AIMS: Some prospective studies show that depression is a risk
      factor for cognitive decline. So far, the explanation for the background of this
      association has remained unclear. The present study investigated 1) whether
      depression is etiologically linked to cognitive decline; 2) whether depression
      and cognitive decline may be the consequence of the same underlying subcortical
      pathology, or 3) whether depression is a reaction to global cognitive
      deterioration. METHODS: A cohort of 133 depressed and 144 non-depressed older
      persons was followed at eight successive observations over 3 years. All subjects
      were participants in the Longitudinal Aging Study Amsterdam (LASA). Depression
      symptoms were measured by means of the CES-D at eight successive waves. Cognitive
      function (memory function, information processing speed, global cognitive
      functioning) was assessed at baseline and at the last CES-D measurement. RESULTS:
      The severity and duration of depressive symptoms were not associated with
      subsequent decline in memory functioning or global cognitive decline. There was
      an association between both chronic mild depression and chronic depression, and
      decline in speed of information processing. CONCLUSIONS: These results support
      the hypothesis that, in older persons, chronic depression as well as cognitive
      decline may be the consequence of the same underlying subcortical pathology.

PMID- 15462467
TI  - The effect of aging on functional decline among older Japanese living in a
      community: a 5-year longitudinal data analysis.
AB  - BACKGROUND AND AIMS: Using longitudinal data analyses, we examined the effects of
      aging on functional decline, based on activities of daily living (ADL) and
      instrumental activities of daily living (IADL) during a 5-year follow-up among
      older people living in a community in Japan. METHODS: The baseline survey in July
      1988 involved all elderly residents aged 60 or older in Saku City, Nagano, Japan
      (N=13418). All survivors of this cohort were asked to participate in follow-up
      surveys conducted in 1989, 1990, 1991, 1992 and 1993. Five items of ADL and five
      of IADL were measured on each survey. A generalized estimating equations (GEE)
      analysis was used to examine the effects of aging on the increase of the
      proportion of subjects with functional dependence. RESULTS: These results
      indicated that the proportion of subjects who were dependent in ADL increased
      during the 5-year period by 2.2 times (p<0.001) and the proportion of those who
      were dependent in either ADL or IADL increased during the same period by 1.8
      times (p<0.001). Gender did not appear to be significantly associated with
      functional decline. CONCLUSIONS: The GEE analysis in this study identified the
      statistically significant effect of aging on the increase of the proportion of
      subjects with functional dependence based on ADL and IADL.

PMID- 15462468
TI  - A flame burning within.
AB  - Inflammation is a human being's primary defense against threats to homeostasis
      that are encountered every day. Especially in old age, when regulatory mechanisms
      responsible for inflammatory responses may be ineffective or damaged, the result
      can be adverse pathological conditions, and an increased risk of morbidity and
      mortality. The inflammation response is a plastic network composed of redundant
      signaling among several different mediators. These mediators have a reciprocal
      relationship with other biological sub-systems, including hormone regulation, the
      autonomic nervous system, and oxidative/anti-oxidant balance. Studying this
      complex architecture requires parallel and multiple research strategies from
      epidemiological to biochemical level, from observational studies to innovative
      intervention approaches. Given that the inflammatory response is a critical age
      related process, understanding its regulatory action is essential in avoiding
      hazardous consequences in old age.

PMID- 15462470
TI  - Decreased cell proliferation and altered cytokine production in frail older
      adults.
AB  - BACKGROUND AND AIMS: Frailty is a geriatric syndrome that predicts increased
      morbidity and mortality. In order to investigate specific immune system
      modulations that may contribute to frailty, eleven age- and sex-matched pairs of
      community-dwelling frail and non-frail older adults were identified. METHODS:
      Peripheral blood mononuclear cells (PBMC) were isolated and PBMC proliferation
      and production of IL-6, tumor necrosis factor (TNF)-alpha, and IL-10 in the
      presence and absence of lipopolysaccharide (LPS) were examined. RESULTS: We found
      that frail subjects had a significantly lower LPS-induced PBMC proliferation
      ratio compared with non-frail subjects (2.1+/-0.9 vs 3.11+/-1.9, p<0.03). In
      addition, frail subjects had higher IL-6 production by PBMC at 48 hours after LPS
      stimulation (35678+/-15637 vs 25178+/-6342 pg/mL, p<0.03). No significant
      differences were observed in TNF-alpha, and IL-10 production between groups.
      CONCLUSIONS: These results suggest that, compared with non-frail controls, frail
      older adults have both decreased LPS-induced proliferation and increased IL-6
      production by PBMC.

PMID- 15462469
TI  - Association between longevity and cytokine gene polymorphisms. A study in
      Sardinian centenarians.
AB  - BACKGROUND AND AIMS: Human longevity seems to be directly correlated with optimal
      functioning of the immune system, suggesting that some genetic determinants of
      longevity reside in those polymorphisms for the immune system genes which
      regulate immune-inflammatory responses, in particular cytokine gene
      polymorphisms. The frequency of -174C single nucleotide polymorphism (SNP) in the
      promoter region of the interleukin (IL)-6 gene is increased in Italian male
      centenarians. Moreover, the frequency of -1082G SNP at the 5' flanking region of
      the IL-10 gene coding sequence is increased among male centenarians, and that of
      +874A SNP at the interferon (IFN)-gamma gene was found more frequently in female
      centenarians. These findings indicate that different alleles at different
      cytokine gene codings for pro- (IL-6, IFN-gamma) or anti-inflammatory (IL-10)
      cytokines may affect the individual life-span expectancy, influencing the type
      and intensity of immune-inflammatory responses against environmental stressors.
      METHODS: In the present study, we analyzed these IL-6, IL-10 and IFN-gamma gene
      polymorphisms in 112 (36 male, 76 female) centenarians from the island of
      Sardinia, whose population shows a genetic background quite different from that
      of mainland Italy, as well as in 137 sixty-year-old controls from the same
      geographic area. RESULTS: No significant differences were observed on analyzing
      IL-6, IL-10 and IFN-gamma polymorphism frequencies among centenarians and
      controls, either on the whole and when the data were analyzed according to
      gender. CONCLUSIONS: These data indicate that gene polymorphisms of cytokines
      playing a major regulatory role in the inflammatory response do not affect life
      expectancy in the Sardinian population. Thus, cytokine/longevity associations
      have a population-specific component, being affected by the population-specific
      gene pool as well as by gene-environment interactions, behaving as survival
      rather than longevity genes.

PMID- 15462471
TI  - Osteophyte-induced dysphagia: an intruding facet of cervical spondylosis in the
      elderly.

PMID- 15462472
TI  - Vitamin B12 deficiency: an unusual cause of falls in the elderly.

PMID- 15462473
TI  - [Imaging methods in liver diseases].
AB  - Imaging methods in liver diseases. The author reviews the diagnostic imaging
      procedures applied most commonly in liver disease in this day and age- with
      special attention to ultrasound imaging. She describes the possibilities,
      performance and disadvantages of the imaging procedures. She makes a
      recommendation for a generally applicable optimal investigative sequence.

PMID- 15462474
TI  - [Comparison of clinical data of two autopsy series, 1938-1951 and 1990-2002, at
      the Debrecen University Department of Neurology].
AB  - BACKGROUND: The clinical parameters of autopsied brains in two periods (1938-1951
      and 1990-2002) were analyzed and compared. METHODS: Gender distribution, age,
      clinical diagnosis, treatment length of 695 (1938-1951) and 1378 (1990-2002)
      autopsies of Department of Neurology, Debrecen, Hungary were investigated.
      RESULT: Between 1938-1951 mean 49.6 +/- 15.5 autopsies/year were performed while
      in the 1990-2002 the autopsies raised to 106 +/- 19.6 /year. In the first period
      almost all deceased patient has been autopsied, but the ratio decreased on 68.9%
      between 1990-2002. The average age of autopsied patients (39.1 +/- 2.9 years)
      almost doubled after 40 years (69.5 +/- 2.0 years). In the first period (1938
      1951) the infectious and tumorous cases were most frequent (33.6% and 31.2%),
      while in the second one, the cerebrovascular diseases dominated (84.5%). There
      was no significant difference between the treatment lengths of two periods (18.1
      and 14.5 days, respectively). CONCLUSIONS: While the absolute number of autopsies
      raised after 40 years, the ratio decreased at our department (from 100% to
      68.9%), similarly to the worldwide trends. The significantly higher age of
      autopsied patients and the different spectrum of clinical diagnosis reflects the
      decrease of infectious diseases and increase of stroke frequency and the ageing
      of the Hungarian population. Authors sustain with literary data that autopsy
      should not be ignored, and are convinced, together with professor Mohr, that
      "autopsy is the ultimate audit of medicine, the yardstick of clinical care and
      research. To dispence with autopsy is an unfortunate trend that certainly
      endangers the value of clinical research."

PMID- 15462475
TI  - [Travel medicine and its correlations with insurance medicine].
AB  - The author describes the basic ideas and skills of travel medicine, as a new
      discipline of medical science in Hungary. He also emphasizes the importance of
      the knowledge of assistance medicine (as a substructure of the travel medicine).
      The author points out that travel medicine should be assigned to the discipline
      of insurance medicine in Hungary. In respect of Hungary's joining the European
      Union, Hungarian doctors should be fully aware of the importance of the
      traveller's medical treatment.

PMID- 15462476
TI  - [Artistic creativity and bipolar mood disorder].
AB  - BACKGROUND: Several studies and theories propose a connection between
      psychopathology and artistic creativity i.e. madness and genius characters share
      common roots. OBJECTIVE: Employing scientific research data, the objective of
      this review is to elucidate the frequency of psychopathological alterations among
      writers and artists and to analyse the possible influence of bipolar mood
      disorder spectrum on the artistic creativity. METHOD: Reviewing studies a) on
      retrospective investigations, based on biographies of famous persons with high
      creative achievements, b) on psychiatric examinations of living writers and
      artists, c) on individual examples of geniuses in the light of their mental
      status and work output correlations, and d) on creative traits and skills of
      diagnosed psychiatric patient populations. RESULTS: Beyond the practical
      experiences and impressions being held for ages from ancient times, the
      scientific observations and surveys indicate that psychopathological symptoms,
      especially those belonging to the bipolar mood disorder (bipolar I and II), major
      depression and cyclothymia categories occur more frequently among writers, poets,
      visual artists and composers, compared to the rates in the general population.
      Self-reports of writers and artists describe symptoms in their intensively
      creative periods which are reminiscent and characteristic of hypomanic states.
      Further, cognitive styles of hypomania (e.g. overinclusive thinking, richness of
      associations) and originality-prone creativity share many common as indicated by
      several authors. Among the eminent artists showing most probably manic-depressive
      or cyclothymic symptoms were: E. Dickinson, E. Hemingway, N. Gogol, A.
      Strindberg, V. Woolf, Lord Byron (G. Gordon), J. W. Goethe, V. van Gogh, F. Goya,
      G. Donizetti, G. F. Handel, O. Klemperer, G. Mahler, R. Schumann, and H. Wolf.
      Based on biographies and other studies, brief descriptions are given in the
      present article on the personality character of Gogol; Strindberg, Van Gogh,
      Handel, Klemperer, Mahler, and Schumann. Further example is the enigmatic silence
      and withdrawal from opera composing of Gioacchino Rossini (1792-1868), which is
      still a matter of various theories and explanations. Until his life of 37 years
      he composed 39 operas and lived almost another 40 years without composing any new
      one. Biographies show that severe depressive sufferings played a role in that
      withdrawal and silence, while in his juvenile years most probably hypomanic
      personality traits contributed to the extreme achievements and very fast
      composing techniques. Analysing the available biographies of Rossini and the
      character of music he composed (e.g. opera buffa, Rossini crescendo) strongly
      suggests the medical diagnosis of a bipolar affective illness. CONCLUSION:
      Comparing to the general population, bipolar mood disorder is highly
      overrepresented among writers and artists. The cognitive and other psychological
      features of artistic creativity resemble many aspects of the hypomanic
      symptomatology. It may be concluded that bipolar mood traits might contribute to
      highly creative achievements in the field of art. At the same time, considering
      the risks, the need of an increased medical care is required.

PMID- 15462477
TI  - [Metastatic endophthalmitis following lung transplantation].
AB  - Intraocular septic--bacterial, viral or fungal--metastasis originating from an
      infectious focus is very rare but serious complication. The authors performed one
      enucleation and one evisceration on two patients because of endophthalmitis
      secondary to pulmonary infection following lung transplantation. The pathogens
      were Pseudomonas aeruginosa and Mycobacterium xenopi respectively. With this case
      report the authors aim to draw attention to a rare, but serious ophthalmic
      complication of organ transplantation: endophthalmitis; its early care, to help
      prevent the need for enucleation.

PMID- 15462478
TI  - [Treatment of patients with high cardiovascular risk in general practice].

PMID- 15462479
TI  - Provider-focused asthma interventions that get results.

PMID- 15462480
TI  - New tool helps physicians get on the front end of CVD.
AB  - While there are already a number of ways to assess whether patients are at risk
      for CAD, the literature suggests these tests may be too burdensome to be done as
      often as they should. However the FDA has just approved a new screening procedure
      that could remove at least some of the barriers. Additionally, early data suggest
      that the new screening test--which measures cholesterol in the skin--gives
      physicians new information that can help them make more informed decisions on
      which patients need further tests or intervention.

PMID- 15462481
TI  - Physician-friendly strategies boost the power and reach of DM.
AB  - Why? Because physicians have a powerful influence over patient behavior, and you
      can accomplish much more with their active and enthusiastic support. Further,
      while physicians may be skeptical or even antagonistic toward DM interventions at
      first, you can take steps to win their confidence and cooperation.

PMID- 15462482
TI  - New program applies principles of DM to transplant patients.
AB  - One of the most common and costly complications related to transplant patients is
      organ rejection due to patient non-compliance. It's a huge issue because of the
      complicated medication regimens transplant patients must learn to deal with, and
      the numerous side-effects involved. For this reason, Aetna decided to offer
      transplant patients extra support in the form of a DM program that focuses on
      medication management, and early indications are the approach is having a
      positive effect.

PMID- 15462483
TI  - Coronary heart disease (CHD) in lupus: round up the usual suspects?

PMID- 15462484
TI  - Relationship between adherence to study and clinic visits in systemic lupus
      erythematosus patients: data from the LUMINA cohort.
AB  - The aim of this study was to examine the relationship between nonadherence with
      study visits and with regularly scheduled clinic visits after adjusting for other
      patient and disease characteristics. One hundred and forty-one LUMINA patients
      with appointment data in the institutions' computerized systems (UAB and UTH)
      were studied. 'No shows' were assessed as the percentage of appointments not
      attended for either rheumatology, other clinics and LUMINA visits (from zero to
      100%). Eighty-nine percent of the patients were women, 40% were Caucasians, 55%
      African-Americans and 5% Hispanics. 'No shows' to rheumatology were associated
      with non-Caucasian ethnicity, younger age, single marital status, lack of home
      ownership, 'no shows' to other clinics and to the LUMINA study, greater disease
      activity and to some disease manifestations (serositis, renal involvement,
      positive anti-dsDNA antibodies). In multivariable analyses, features predictive
      of rheumatology 'no shows' were lack of home ownership, 'no shows' to LUMINA
      study visits, renal involvement and serosal manifestations. Nonadherence with
      study visits and with regularly scheduled care at rheumatology clinics were
      associated. Other factors predictive of nonadherence to recommended care were
      lack of home ownership (a measurement of low socioeconomic status) and the
      presence of disease manifestations (i.e., renal or serosal involvement). These
      data should be considered when caring for patients with SLE.

PMID- 15462485
TI  - Risk of ovarian failure and pregnancy outcome in patients with lupus nephritis
      treated with intravenous cyclophosphamide pulse therapy.
AB  - This study was designed to investigate the risk of ovarian failure and the
      pregnancy outcomes in women treated with intravenous cyclophosphamide (IVCYC)
      pulse therapy for lupus nephritis. Sixty-seven women with proliferative lupus
      nephritis were studied. The clinical and laboratory data, SLEDAI and damage
      indices at IVCYC initiation, doses and numbers of IVCYC pulses, pregnancy and
      fetal outcomes were evaluated. During a follow-up of 74.4+/-20.6 months,
      amenorrhea occurred in 25 (37.3%) and was sustained permanently in 10 patients
      (14.9%). Thirteen women became pregnant with a total of 19 pregnancies. Seventeen
      pregnancies ended without complications and all babies were born healthy without
      any congenital anomalies or perinatal illnesses. Two pregnancies were terminated
      by induced abortion but no congenital anomaly was noted in these cases. Logistic
      regression analysis showed that old age, high damage index at the initiation of
      IVCYC pulse therapy and high cumulative dosage of IVCYC were the independent risk
      factors of ovarian failure, and that the presence of amenorrhea, regardless of
      its duration, was the risk factor of pregnancy failure. Pregnancy was possible
      with a favorable outcome after the withdrawal of IVCYC pulse therapy, unless
      amenorrhea develops.

PMID- 15462486
TI  - Analysis of molecular heterogeneity of prolactin in human systemic lupus
      erythematosus.
AB  - Hyperprolactinemia without clinical manifestations has been reported in some
      patients with systemic lupus erythematosus (SLE) because an increase of prolactin
      (PRL) is produced due to the BIG/BIG molecular variant (molecular variant < 150
      kD). This research project aimed to determine levels of PRL: its bioactive form,
      the little nonglycosylated form (NGPRL) and variants with decreased bioactivity
      such as the BIG/BIG and the little glycosylated (GPRL), in 29 women and five men
      with SLE. PRL was assayed by IRMA with a kit from Immunotech Laboratory, the
      BIG/BIG form by precipitation with polyethyleneglycol 6000, and the NGPRL and
      GPRL by chromatography on Concanavalin-A- Sepharose. Increased PRL was detected
      in seven patients (20.6%) of whom three had increased BIG/BIG, six had increased
      GPRL and only four had increased NGPRL. The three cases with increased BIG/BIG
      were contrasted by chromatography on Sephadex G-100. No increased PRL or any of
      the other variants assayed were found in men. Results were similar when PRL was
      evaluated in the same blood samples by a different IRMA (DPC Laboratory). The
      etiology of the hyperprolactinemia in some of these patients is unknown, but
      their lack of symptoms (galactorrhea or amenorrhea) could be due to the BIG/BIG
      forms and basically to the glycosylation of the hormone. As for the relation
      between PRL and SLE activity, we found that hyperprolactinemic patients were
      younger, had a shorter history of illness, although it was not statistically
      significant, and a higher SLEDAI score. This would indicate a relation between
      hyperprolactinemia and lupus activity. The patients with increased BIG/BIG form
      also had a very active illness at the time of the study.

PMID- 15462487
TI  - Antineutrophil autoantibodies and their target antigens in systemic lupus
      erythematosus.
AB  - Various autoantibodies have been identified in sera from patients with systemic
      lupus erythematosus (SLE) and autoantibodies against neutrophil have been
      reported. It was suggested that antineutrophil autoantibodies might be involved
      in the pathogenesis of neutrocytopenia; however, the role of autoantibodies
      against neutrophil precursors and their specific target autoantigen(s) remained
      further characterized. The objective was to investigate the target antigens and
      clinical associations of autoantibodies against neutrophils and neutrophil
      precursors in patients with SLE. Sera were collected from 92 patients with SLE
      and renal biopsy proven lupus nephritis. Cell lysates of peripheral neutrophils
      (as mature neutrophils) from a normal blood donor and white blood cells from a
      patient with blast crisis of chronic granulocytic leukemia (CGL) (as neutrophil
      precursors) were used as antigens in Western blot analysis to detect
      autoantibodies in sera from patients with SLE. The clinical significance of
      antineutrophil autoantibodies that recognized different antigens were further
      analysed. Using normal peripheral neutrophils as antigens, two bands could be
      blotted: 64 kD (33/92, 35.9%) and 50 kD (13/92, 14.1%). The prevalence of anti-64
      kD autoantibody in patients with positive rheumatic factor was significantly
      higher than that in patients without (54.5 versus 18.8%, P < 0.05). Using CGL
      white cells as antigen, five bands could be blotted: 60 kD (34/92, 37.0%), 50 kD
      (32/92, 34.8%), 29 kD (27/92, 29.3%), 42 kD (19/92, 20.7%) and 18 kD (16/92,
      17.4%). The prevalence of anti-60 kD autoantibody was significantly higher in
      patients with neutrocytopenia than that in patients without neutrocytopenia (100
      versus 48.3%, P < 0.01). The prevalence of anti-29 kD autoantibody was
      significantly higher in patients with alopecia than that in patients without
      alopecia (45.8 versus 20.8%, P < 0.05). Furthermore, the prevalences of anti-60
      kD, anti-50 kD and anti-42 kD autoantibodies were significantly higher in
      patients with anti-Ro autoantibody than those in patients without; the
      prevalences of anti-29 kD and anti-18 kD autoantibodies were significantly higher
      in patients with anti-Sm autoantibody than those in patients without. We conclude
      that there are heterogeneous autoantibodies against both neutrophils and their
      precursors in sera from patients with SLE. Different autoantibodies may have
      different clinical significance.

PMID- 15462488
TI  - Impaired brachial artery endothelium dependent flow mediated dilation in systemic
      lupus erythematosus: preliminary observations.
AB  - Our objective was to compare brachial artery endothelium dependent and
      independent vasodilation in lupus patients and healthy females, by means of high
      resolution noninvasive brachial artery ultrasound. Endothelially mediated
      vasodilation was estimated noninvasively by examination of brachial artery
      responses to postischemic reactive hyperemia and endothelial independent
      vasodilation from response to sublingual glycerlynitrate (GTN) using high
      resolution external vascular ultrasound. Five patients with known coronary artery
      disease (CAD), five with subclinical CAD, five with no CAD and five control
      subjects were assessed. Endothelium dependent vasodilation was significantly
      blunted in lupus patients with CAD as compared with healthy female controls (0.11
      versus 11.1%, P = 0.018). Corresponding values for lupus patients with
      subclinical CAD and no CAD were 11 and 9.6%, respectively. For each subject,
      endothelium dependent vasodilation (EDV) was related to endothelium independent
      vasodilation (EIV) to adjust for varying vascular smooth muscle responses to GTN
      in individual subjects. This ratio was markedly depressed in lupus patients with
      CAD as compared with control subjects (0.12 versus 1.15). The corresponding
      EDV/EIV ratios for patients with subclinical CAD and no CAD were similar at 0.69
      and 0.65, respectively. The conclusion was that flow mediated vasodilation in
      lupus patients with coronary artery disease is markedly depressed as compared to
      healthy subjects.

PMID- 15462489
TI  - The basement membrane zone in patients with systemic lupus erythematosus:
      immunofluorescence studies in the skin, kidney and amniochorion.
AB  - Histological studies suggest that the basement membrane zone (BMZ) is the main
      target of tissue pathology in cutaneous lupus erythematosus (LE). The BMZ is
      characteristically thickened and is the site of deposition of autoantibodies in
      LE. Alteration of some (BMZ) macromolecules is implicated in the pathology of
      several bullous skin diseases. A major component of BMZ is heparan sulphate
      proteoglycan (HSPG) which was found reduced in the skin of some patients with
      systemic lupus erythematosus (SLE) and in the kidney of mice with lupus
      nephritis. Similar to the skin, amnion is derived from the ectodermal germ layer
      during embryogenesis and expression of BMZ components of amniochorion was not
      previously studied in SLE. The aim of the present study was to investigate the
      expression of major BMZ macromolecules in the skin, kidney and amnioplacentae
      obtained from patients with SLE and compare these findings with organ biopsies
      from unaffected individuals. In addition, determining whether the differences in
      composition and distribution of BMZ macromolecules in these organs correlate with
      certain patterns of deposition of immunoreactants could contribute to our
      understanding of the mechanism of deposition of immunoreactants in SLE. In some
      patients with SLE, reduced expression of HSPG in nonlesional skin was reported
      previously. These changes of heparan sulphate might be important in the
      pathogenesis of LE. Therefore, the aims of this study are to confirm the previous
      finding and to compare HSPG expression between lesional and nonlesional LE skin.
      The unique features of each BMZ could contribute to the deposition or binding of
      positively charged immune complexes and explain the different patterns of
      immunofluorescence. Frozen sections of skin, kidney and amniochorion obtained
      from patients with SLE were investigated by indirect immunofluorescence technique
      using monoclonal antibodies (Moab) to determine the expression of major
      components of the BMZ. Heparan sulfate expression is reduced in the skin and, to
      a lesser extent, in the kidney in patients with SLE. There was no correlation
      between the kidney and skin heparan sulfate expression within the same patient.
      The BMZ composition in amniochorionic membrane ofplacentae from women with SLE
      was normal. Heparan sulfate may be one of the major targets for immunoglobulin
      deposition in the skin of patients with SLE. The processes of immunoglobulin
      deposition in SLE may be more complex in that there was no correlation between
      heparan sulfate expression in the skin and kidney of the same patient.

PMID- 15462490
TI  - Double-blind, randomized, placebo-controlled pilot study of leflunomide in
      systemic lupus erythematosus.
AB  - Twelve systemic lupus erythematosus (SLE) patients with mild to moderate disease
      activity (SLEDAI of > or = 6 and on prednisolone < 0.5 mg/kg/day) were included
      in a prospective, randomized, double-blind, placebo-controlled pilot study for 24
      weeks. Six were randomized to receive oral leflunomide and six received placebo.
      Primary outcome of this study included the mean change of SLEDAI at 24 weeks.
      Secondary outcomes included the changes in proteinuria, complement levels, anti
      ds-DNA binding, and prednisolone dosage. The mean age of the 12 patients was 41+/
      9 years, and the mean disease duration was 8.5+/-5.8 years. All were female
      except one patient. The disease activity of both groups of patients decreased
      significantly after six months of treatment (14.7+/-6.0 to 3.7+/-2.3 in
      leflunomide group, P = 0.028, and 9.7+/-3.4 to 5.2+/-4.1 in placebo group, P =
      0.027). Reduction in the SLEDAI from baseline to 24 weeks was significantly
      greater in the leflunomide group than the placebo group (11.0+/-6.1 in the
      leflunomide group and 4.5+/-2.4 in the placebo group respectively, P = 0.026).
      Minor adverse events included transient elevation in ALT, hypertension and
      transient leucopenia. In summary, leflunomide was more effective than placebo in
      treating SLE patients with mild to moderate disease activity and was safe and
      well-tolerated.

PMID- 15462491
TI  - IL-1RA in refractory systemic lupus erythematosus.
AB  - There is evidence from animal and human studies that IL-1 might play an important
      role in the development and maintainence of inflammation in systemic lupus
      erythemathosus (SLE). We hypothesized that, in SLE, there might be a relative
      deficiency in the physiologic antagonist of IL-1, IL-1 receptor antagonist (IL
      1RA). We therefore treated three patients with active SLE in whom conventional
      therapy has failed with the human IL-1RA, Anakinra. In two of the three patients
      there was a transient effect on muscle pain and/or polyarthritis. In one patient
      with lupus myositis there was no effect at all. The therapy was well tolerated
      and the only significant side effect was a transient drop in complement levels
      (C3 and C4) without clinical or laboratory signs of increased SLE activity in all
      three patients.

PMID- 15462492
TI  - Susac's syndrome or catastrophic antiphospholipid syndrome?
AB  - Susac's syndrome is a microangiopathic disorder of unknown pathogenesis
      presenting with encephalopathy, hearing loss and branch retinal artery
      occlusions. The term 'catastrophic' antiphospholipid syndrome (APS) is used to
      define a subset of the APS characterized by thrombotic microangiopathy with
      clinical evidence of three or more organ involvement developed in a short period
      of time. We describe a patient with typical features of Susac's syndrome, that
      appeared in less than a week, in whom aPL were detected, thus fulfilling criteria
      for 'probable' catastrophic APS.

PMID- 15462493
TI  - Nephrogenic fibrosing dermopathy in two patients with systemic lupus
      erythematosus.
AB  - Nephrogenic fibrosing dermopathy (NFD) is a novel fibrosing disorder of the skin
      with characteristic histopathology. It affects patients with impaired renal
      function and appears to be independent from the type of kidney disease. Its
      aetiopathology is unknown and presently no standard therapy exists. We report a
      patient with systemic lupus erythematosus (SLE) and glomerulonephritis who
      developed diffuse indurated erythematous plaques covering nearly the entire legs
      and trunk. She had never received dialysis. The second patient suffered from SLE
      and antiphospholipid syndrome related thrombotic glomerulopathy. After 10 weeks
      of haemodialysis she developed the same skin condition. To the best of our
      knowledge, these are the first reports of NFD occurring in patients with SLE.

PMID- 15462494
TI  - Systemic lupus erythematosus in Kuwaiti children: organ system involvement and
      serological findings.
AB  - The course and severity of systemic lupus erythematosus (SLE) in children is
      generally similar to the adult form with potential serious organ system
      involvement, there are, however, factors that influence the prevalence and
      clinical behavior of the disease. Our objective was to analyse the organ system
      involvement and immunological findings in Kuwaiti children with SLE in relation
      to gender and age of onset and compare these findings to that in published
      reports. Organ system involvement and serologic profiles were analysed in 35
      children with SLE. The major organ systems studied were: renal, hematological,
      cardiac, pulmonary, hepatic and the central nervous system. The prevalence of
      ANA, anti-dsDNA, anti-Sm, SSA, SSB and anti-cardiolipin antibodies were studied
      in addition to complement C3 and C4 levels. The results showed that a high
      percentage of children had hematological involvement (34%); thrombocytopenia
      (23%) and hemolytic anemia (20%). Renal involvement was proven by biopsy in only
      10 children (29%). Neuropsychiatric manifestations were seen in five (14%) of
      patients. Males had a tendency for major organ involvement relative to females.
      All patients had positive ANA tests. All males had positive anti-dsDNA tests
      compared to 86% of female patients. The most significant finding in this study is
      the high frequency of hematological manifestations and the relatively low
      incidence of renal disease and neuropsychiatric abnormalities in Kuwaiti children
      with SLE.

PMID- 15462495
TI  - Factors associated with chloroquine-induced retinopathy in rheumatic diseases:
      comments on the article by Araiza-Casillas et al.

PMID- 15462496
TI  - Augmented expression of chromogranin A and serotonin in peri-malignant benign
      prostate epithelium as compared to adenocarcinoma.
AB  - There is a growing body of evidence that the occurrence of neuroendocrine (NE)
      differentiation in prostate carcinoma correlates with poor prognosis, tumor
      progression, and androgen-independence. In the present study, the expression of
      common NE markers, i.e., chromogranin A (ChGA), serotonin (5HT), neuron-specific
      enolase (NSE) and adrenomedullin (AM), was retrospectively examined in formalin
      fixed, paraffin-embedded prostate tissue samples obtained from patients with
      adenocarcinoma and from patients with nodular hyperplasia of the prostatic gland
      (NHPG) (33 and 28, respectively). The statistical analysis of the results (tested
      the equality of matched pairs of observations using the Wilcoxon matched-pairs
      signed ranks test) revealed a more prominent expression of ChGA in benign
      epithelial cells adjacent to adenocarcinomatic lesions (Peri-PAC) than in the
      adenocarcinoma (PAC) (p = 0.0049). A similar pattern of expression was detected
      for 5HT (p = 0.000). When comparing the expression of ChGA and 5HT in tissue
      samples originating in cancer patients with those obtained from NHPG samples,
      more ChGA and 5HT were expressed in Peri-PAC than in NHPG (p = 0.0004 and 0.002,
      respectively). The results obtained raise the possibility that adenocarcinoma
      cells urge some adjacent benign epithelial cells to differentiate into NE cells,
      which, in turn, may promote tumor growth and invasion.

PMID- 15462497
TI  - Prognostic significance of anaplasia and angiogenesis in childhood
      medulloblastoma: a pediatric oncology group study.
AB  - The purpose of this study was to investigate whether quantitative assessment of
      cytologic anaplasia and angiogenesis may predict the clinical prognosis in
      medulloblastoma and stratify the patients to avoid both undertreatment and
      overtreatment. Medulloblastomas from 23 patients belonging to the Pediatric
      Oncology Group were evaluated with respect to some prognostic variables,
      including histologic assessment of nodularity and desmoplasia, grading of
      anaplasia, measurement of nuclear size, mitotic cell count, quantification of
      angiogenesis, including vascular surface density (VSD) and microvessel number
      (NVES), and immunohistochemical scoring of vascular endothelial growth factor
      (VEGF) expression. Univariate and multivariate analyses for prognostic indicators
      for survival were performed. Univariate analysis revealed that extensive
      nodularity was a significant favorable prognostic factor, whereas the presence of
      anaplasia, increased nuclear size, mitotic rate, VSD, and NVES were significant
      unfavorable prognostic factors. Using multivariate analysis, increased nuclear
      size was found to be an independent unfavorable prognostic factor for survival.
      Neither the presence of desmoplasia nor VEGF expression was significantly related
      to patient survival. Although care must be taken not to overstate the importance
      of the results of this single-institution preliminary report, pathologic grading
      of medulloblastomas with respect to grading of anaplasia and quantification of
      nodularity, nuclear size, and microvessel profiles may be clinically useful for
      the treatment of medulloblastomas. Further validation of the independent
      prognostic significance of nuclear size in stratifying patients is required.

PMID- 15462498
TI  - The HOPE-technique permits Northern blot and microarray analyses in paraffin
      embedded tissues.
AB  - There is an increasing demand for tissue samples that, after having been used for
      conventional histologic examination, are also suited for molecular analyses. As
      to formalin-fixed, paraffin embedded (FFPE) tissue, the latter applications are
      very limited. The HOPE (Hepes-Glutamic acid buffer mediated Organic solvent
      Protection Effect) technique comprises a new protection-solution with an organic
      buffer, with acetone as the only dehydrating agent, and pure paraffin of 52-54
      degrees C melting temperature, allowing for all pathologic routine
      investigations. In contrast to FFPE tissue, the HOPE-technique allows for the
      application of molecular methods, such as high molecular DNA and RNA isolation,
      which can be used for PCR and reverse transcription PCR (RT-PCR). In this study,
      we investigated whether RNA from HOPE-fixed tissue samples is suitable for
      Northern blot and microarray analyses. RNAs of two HOPE-fixed breast cancer
      specimens of different histologic grade were used to carry out an array
      experiment. It turned out that RNA from HOPE-fixed tissue is of high quality and
      can be successfully used for array experiments. In addition, by detecting GAPDH
      and high mobility group protein gene B1 (HMGB1)-specific transcripts, we were
      able to demonstrate that RNA from HOPE-fixed tissue can also be used for Northern
      blot hybridization.

PMID- 15462499
TI  - Growth pattern correlates with the distribution of basement membrane and
      prognosis in lung adenocarcinoma.
AB  - Lung adenocarcinoma frequently has a histologic heterogeneity, particularly with
      regard to its cell morphology and growth pattern, with or without stromal
      desmoplasia. However, little is known about the relationship between morphologic
      heterogeneity and the destruction of BM. We selected 147 foci showing different
      growth patterns studied in 76 patients with lung adenocarcinoma and examined
      immunohistochemically the distribution of BM antigens, as well as the expression
      of MMPs and TIMP-2. BM antigens were more highly preserved in foci of the BAC
      growth pattern (94.7%) than in those of the papillary/acinar (24.5%) and solid
      patterns (16.1%) (p<0.01). MMP-2-positive cancer cells were significantly more
      frequent in poorly preserved foci of BM antigens than in preserved foci (p<0.05).
      The population of TIMP-2-positive cancer cells showed a positive correlation with
      BM preservation (p<0.05). However, no significant relationship between growth
      pattern and expression of MMP-9 and -14 was found. BM antigens had almost totally
      disappeared in desmoplastic foci. Multivariate analyses revealed that pathologic
      stage and high expression of TIMP-2 were independent prognostic factors. These
      findings indicate that the histologic heterogeneity of lung adenocarcinomas is
      partly related to the cancer cell-stromal interaction, in particular through BM
      preservation or destruction, which was mainly affected by cancer cell expression
      of MMP-2 and TIMP-2 in lung adenocarcinomas.

PMID- 15462500
TI  - A comparative histopathological evaluation of sacs from boys and girls with
      inguinal hernia.
AB  - The purpose of this study is to determine and to compare histopathologic
      alterations of hernia sacs obtained from patients with inguinal hernia with those
      of the peritoneal tissue from patients operated on for other abdominal disorders.
      Samples were obtained from 42 pediatric patients with uni- or bilateral hernias,
      and from 30 pediatric control patients without hernia. Sections were stained with
      hematoxylin-eosin, Gomori's trichrome, and Gomori's reticulin. Furthermore, they
      were immunohistochemically stained with anti-synaptophysin for the quantification
      of neural structures. All the slides were examined for six parameters, including
      variations in tissue and collagen types, the presence of inflammation and
      proliferation of vessels, neural plexus, and mesothelial cells. The results were
      evaluated statistically using the independent T-test and the Mann-Whitney-U test.
      Parametric tests revealed a higher presence of large neural plexus (p = 0.003),
      increased proliferation of mesothelial cells (p = 0.009), and
      hypervascularization (p = 0.003) in sacs of the hernia group. There were also
      major changes that were dependent on the sex of the patients. Most part of hernia
      sacs tissue was found to be fibrous and adipose in most boy patients, but was
      fibro-muscular in girls with inguinal hernia (male/female p = 0.03), while the
      tissues were fibro-adipose in both sexes in the control group (inguinal
      hernia/control p = 0.016). Similarly, vascular proliferation was mainly
      encountered in hernia sacs of girls (p = 0.013). These features were not observed
      in the control groups. Therefore, on the basis of sex, we determined whether or
      not these findings could indicate the difference between the etiopathologic
      mechanisms of inguinal hernias. Furthermore, we went into the question of whether
      or not the comprehensive examination of hernia sacs sufficed to enlighten the
      etiology of hernias.

PMID- 15462501
TI  - Spindle cell rhabdomyosarcoma of the tongue in an infant: a case report with
      emphasis on differential diagnosis of childhood spindle cell lesions.
AB  - Malignant tumors are extremely uncommon in infants, specifically in the head and
      neck region. We present a three-day-old infant with a large, polypoid, soft
      tissue mass arising from the floor of the mouth. Histologically, this neoplasm
      consisted of hypercellular and myxoid areas. A mixture of poorly oriented, small,
      undifferentiated, hyperchromatic, and round to elongate spindle cells was seen. A
      high degree of striated muscle differentiation was present, along with areas
      marked by a herringbone pattern, as well as hemangiopericytic vessels and rare
      mitosis. Immunohistochemical examinations revealed strong nuclear staining for
      myogenin and diffuse cytoplasmic staining for desmin and muscle-specific actin
      (HHF-35). The tumor did not stain for S-100. Based on histologic results and
      immunostains, this lesion was diagnosed as spindle cell rhabdomyosarcoma. This
      type of lesion involving the tongue is rarely seen in females, neither in
      association with a herringbone pattern nor with hemangiopericytic vessels.
      Furthermore, rare benign and malignant spindle lesions, such as cellular
      fibromatosis, fetal rhabdomyoma, infantile hemangiopericytoma, infantile
      rhabdomyofibrosarcoma, and infantile fibrosarcoma, should be in the differential
      diagnosis and excluded.

PMID- 15462502
TI  - Epithelioid variant of pleomorphic liposarcoma: report of a case.
AB  - A case of an epithelioid variant of pleomorphic liposarcoma (PL) arising in the
      back of a 72-year old male is presented. The lesion was a well-circumscribed but
      unencapsulated, yellowish white mass measuring 11 x 10 x 9 cm in the subcutis and
      muscle. Histologically, the tumor consisted of three elements; an epithelioid
      cell element occupying about 50%, a lipogenic and mixed lipogenic and epithelioid
      cell element occupying 40%, and a malignant fibrous histiocytoma-like element.
      The lipogenic area was composed of uni- and multivacuolated pleomorphic
      lipoblasts. Immunohistochemically, the tumor was positive for vimentin,
      epithelial membrane antigen, and CD10. It was negative for desmin, alpha-smooth
      muscle actin, muscle actin, S-100 protein, and cytokeratins 8 and 18. The
      epithelioid variant of PL should be differentiated from metastatic renal cell
      carcinoma and adrenal cortical adenocarcinoma.

PMID- 15462503
TI  - Bone marrow metastasis of angiosarcoma.
AB  - We report a rare finding of bone marrow metastasis from an angiosarcoma. The
      patient was a 36-year-old man who initially presented with a high-grade
      angiosarcoma of the spleen and was treated with splenectomy and chemotherapy. He
      developed leukoerythroblastic anemia three years after splenectomy. Bone marrow
      biopsy revealed extensive infiltrate by angiosarcoma with typical features of
      spindle tumor cells and anastomosing vascular channels. The immunohistochemistry
      showed tumor cells positive for the endothelial markers of CD31, CD34, and von
      Willebrand factor. Angiosarcomas are rare and aggressive tumors. Although
      metastases occur commonly, bone marrow findings have been rarely documented. We
      have found in the literature two other cases of bone marrow metastasis of
      angiosarcoma, and all these patients had a primary tumor of the spleen. It would
      seem that splenic angiosarcomas have a virtually unique propensity for
      infiltration in the bone marrow.

PMID- 15462504
TI  - Follicular lymphoma of the skin and superficial soft tissues associated with a
      prominent follicular dendritic cell proliferation: an unusual pattern which may
      represent a diagnostic pitfall.
AB  - We describe two elderly patients with follicular lymphoma (FL) involving the skin
      and superficial soft tissues, with a striking proliferation of follicular
      dendritic cells (FDC). In addition, one patient had bone marrow involvement by
      FL. Histopathologically, the most remarkable feature in both cases seen at low
      magnification was a striking pallor of the constituent cells, which were arranged
      in fascicles, whorls, and round islands. The majority of the cells had the
      typical cytologic features of FDCs. They were intimately intermingled with
      centroblasts and centrocytes. A large amount of the clear cytoplasm and the pale
      nuclei of FDCs, which predominated in the tumors, caused the striking overall
      pallor of the lesions. Small reactive lymphocytes were scattered between the
      fascicles. A vague follicular growth pattern was seen only focally. The mantle
      zones were markedly reduced or absent so that the follicles were seen lying
      unseparated. The close intermixture of the FDCs and the germinal center cells was
      responsible for the FDCs appearing to be decorated with B-associated marker, and
      the germinal center cells seemed to be stained to some degree with FDC-markers.
      The tumor bulk demonstrated a diffuse and strong reaction with CD10, CD20, CD21,
      CD35, and stained weakly with CD79a. Fascin and CD23 showed only a weak and focal
      staining pattern. Bcl-2 decorated large centroblasts and small reactive T-cells.
      The tumor bulk was negative for actin, EMA, cytokeratins, vimentin, desmin, and
      factor XIIIa. The proliferative index was rather low; MIB-1 mainly decorated
      large centroblasts. No monoclonal rearrangement of IgH genes was detected.
      Epstein-Barr virus was not identified. Electron microscopy revealed typical
      features of FDCs intermingled with germinal center cells. Such cases may
      represent a diagnostic pitfall, as FDC overgrowth can mask FL and give the
      neoplasm the appearance of FDC sarcoma/tumor. We believe that, in both cases, the
      FDC proliferation had a reactive character.

PMID- 15462505
TI  - Mucoepidermoid carcinoma of the thymus: a case presentation and a literature
      review.
AB  - Mucoepidermoid carcinoma of the thymus is an unusual, but well-recognized variant
      of thymic malignant tumors. Its biologic behavior generally depends on the degree
      of differentiation and the amount of cellular atypia. High grade tumors can be
      aggressive neoplasms with a tendency to invade and develop metastases. We report
      on a case of a 53-year-old man, who presented chest discomfort, dyspnea, and
      weakness. As heart function tests were normal, the patient underwent radiologic
      examination, which showed a well-demarcated mass in the anterior mediastinum.
      Histologic examination of the surgically resected mass showed features of a
      mucoepidermoid carcinoma with associated infiltration of the pleural tissue.
      Postoperative radiotherapy and chemotherapy were performed, and the patient died
      two months after initial diagnosis. In case of the absence of metastatic disease
      or other common primary neoplasms of the thymus, the diagnosis of a
      mucoepidermoid thymic carcinoma should be taken into consideration, although this
      tumor is rare.

PMID- 15462506
TI  - Acinic cell carcinoma with follicular pattern of the soft palate.
AB  - Acinic cell carcinoma (ACC) is an uncommon low-grade malignancy of the salivary
      glands. Most cases occur in the major salivary gland, but a few cases affecting
      the minor salivary gland have also been described. Although various growth
      patterns have been reported in the literature, a few cases have been diagnosed as
      ACC with follicular pattern. We present a rare case of ACC with follicular
      pattern of the soft palate in a 60-year-old man. The occurrence of ACC in this
      area is extremely rare, and its striking thyroid-like appearance may cause
      confusion in the differential diagnosis.

PMID- 15462507
TI  - Excellent outcome following transplantation of a domino donor liver with high
      grade macrosteatosis.
AB  - Severe macrosteatosis in the donor liver is considered a major predictive factor
      of primary graft non-function. Such livers are usually discarded despite an ever
      growing need for donor livers. We report our recent experience in a patient (#1)
      who had an excellent outcome following liver transplantation (LT) of a 65-70%
      macrosteatotic graft and compare his findings with those of two other (#2 and #3)
      recipients of moderate to severe macrosteatotic grafts. Both patients (#2 and #3)
      had initial diminished function, with recovery in patient #2 but delayed graft
      non-function requiring re-LT (day 24) in patient #3. Patient #1 had no intra
      operative complications, while patient #2 had mild complications due to prior
      adhesions and graft capsular laceration. In patient #3, extensive intra-abdominal
      adhesions resulting in excessive bleeding occurred during recipient hepatectomy.
      Total ischemic times: 2.48, 6.10, and 8.18 h; total blood product usage: 43, 81,
      and 223 units; post-LT hospital stay: 9, 21, and 69 days were seen in patients
      #1, #2 and #3, respectively. In conclusion, post-LT excellent graft function was
      seen in one recipient of 65-70% macrosteatotic graft. Transplantation of grafts
      with moderate/severe macrosteatosis may be inadvisable in patients with extensive
      intra-abdominal adhesions with expectant excessive bleeding and long ischemia
      times.

PMID- 15462509
TI  - (18f)fluoro-deoxyglucose positron emission tomography in patients with fever of
      unknown origin.

PMID- 15462508
TI  - Transplantation as a therapeutic option for diabetic nephropathy.
AB  - Diabetic nephropathy affects both type 1 and type 2 diabetic patients with a
      frequency of 20-30%. The first sign is microalbuminuria within a range of 30-300
      mg/24h, frequently evolving towards frank proteinuria and renal failure. Tight
      glucose control, control of arterial hypertension with the use of ACEi or ARB can
      retard progression. Once renal failure is established, kidney transplantation can
      be considered for type 1 and type 2 diabetic patients. Quality of life and
      survival are improved with this procedure. In type 1 diabetes, simultaneous
      grafting of a kidney and pancreas considerably improves quality of life and
      diabetic complications. Surgical and infectious complications are sporadic
      drawbacks of this procedure. Pancreas transplantation alone (PTA) remains
      controversial, since a retrospective study in 2003 by Venstrom concluded that
      survival for PTA patients is worse than for comparable patients remaining on the
      waiting list. PTA can be considered for type 1 diabetic patients without advanced
      renal failure with severe and frequent metabolic instability (hypoglycaemia,
      ketoacidosis). Islet transplantation is still an experimental but promising
      procedure in highly selected patients, avoiding major abdominal surgery.

PMID- 15462510
TI  - 18-fluoro-deoxyglucose positron emission tomography may contribute to the
      diagnosis and follow-up of malakoplakia.
AB  - Malakoplakia is a rare inflammatory disease involving most frequently the urinary
      tract. We present a case of bilateral renal malakoplakia, in which FDG-PET
      contributed to diagnosis. We made this diagnosis on the basis of clinical
      presentation, renal biopsy showing a mixed cellular infiltrate with granuloma
      formation and possible Michaelis-Gutmann bodies, resolution of the lesions after
      prolonged antibiotic therapy and evidence of leukocyte dysfunction. We briefly
      discuss the pathophysiology and therapy of this rare and difficult to prove
      disease and the role of FDG-PET in the diagnosis of inflammatory and infectious
      diseases.

PMID- 15462511
TI  - Clinical and pathological features of 14 non-Hodgkin's lymphomas associated with
      coeliac disease.
AB  - BACKGROUND: It is well established that enteropathy associated T-cell lymphoma is
      associated with malabsorption which is due to gluten sensitivity (coeliac
      disease). Our study was performed to define the clinical features, histological
      subtypes, response to treatment, and outcome of the association of coeliac
      disease and T-cell lymphoma. PATIENTS AND METHODS: A retrospective study was
      performed in the UCL Group of Hematology to collect data on patients with a
      diagnosis of non-Hodgkin's lymphoma and coeliac disease. Fifteen cases were
      observed between 1985 and 1999. Case records for all but one patient were
      available and the pathological specimens of 14 patients were reviewed by two
      pathologists. RESULTS: Six previously diagnosed coeliac patients developed
      lymphoma; interval between coeliac symptoms and onset of the lymphoma ranged from
      2 to 48 years (median 16 years). Five patients had coeliac disease and non
      Hodgkin's lymphoma diagnosed concomitantly or less than 6 months before the
      symptoms leading to the diagnosis of lymphoma. Three patients had the diagnosis
      of coeliac disease after lymphoma diagnosis (1, 8 and 10 years later
      respectively). Ten non-Hodgkin's lymphomas were of T-cell origin and 4 were B
      cell lymphomas. Eight out of 14 presented on a surgical emergency. Thirteen were
      treated using chemotherapy. The median survival from the diagnosis of enteropathy
      associated T-cell lymphoma was 12 months (range 1-126). CONCLUSIONS: Lymphomas
      associated with coeliac disease are heterogeneous and their diagnosis is
      difficult. The enteropathy-associated T-cell lymphoma is the most frequent,
      aggressive and fatal complication of coeliac disease but it is not rare to
      observe association with B-cell lymphoma. Chemotherapy is highly toxic in those
      patients. Despite a poor prognosis, long-term survival can be expected in a
      fraction of these patients.

PMID- 15462512
TI  - Antimicrobial drug resistance in nontyphoid human Salmonella in Belgium: trends
      for the period 2000-2002.
AB  - In order to assess antimicrobial resistance in nontyphoid human Salmonella in
      Belgium, the six most important serovars, representing together more than 90% of
      laboratory confirmed cases, were randomly sampled. From June 2000 until December
      2002, a total of 1756 isolates were screened for their antimicrobial resistance
      profile by the disc diffusion method. S. Hadar strains showed the highest level
      of antimicrobial resistance. Simultaneous resistance to ampicillin, nalidixic
      acid, tetracycline and streptomycin was observed in 81.5, 58 and 76.1% of these
      isolates in 2000, 2001 and 2002, respectively. All S. Hadar isolates resistant to
      nalidixic acid also displayed decreased susceptibility to ciprofloxacin (MIC50
      values of 0.25 microg/mL in 2000-2001 and 0.19 microg/mL in 2002). In 2000, 2001
      and 2002, respectively 44.6, 46 and 36.5% of S. Typhimurium isolates were
      multiresistant (resistant to 4 or more antimicrobial agents). These
      multiresistant isolates were preferably associated with a few phage types, such
      as DT104. Complete resistance to ciprofloxacin was detected in three S.
      Typhimurium isolates and sequencing of the gyrA gene revealed for each isolate
      two mutations at codons corresponding to Ser-83 and Asp-87. Multiresistance was
      also common in S. Virchow (7.7%, 15.9% and 29.7%, in 2000, 2001 and 2002,
      respectively). Resistance to nalidixic acid in S. Virchow isolates increased from
      46.2% in 2000 to 80.9% in 2002 and six S. Virchow isolates were detected as
      cefotaxime resistant. In contrast, the vast majority of S. Enteritidis, S.
      Brandenburg and S. Derby isolates remained sensitive to almost all antimicrobial
      agents tested.

PMID- 15462514
TI  - Klebsiella and E. coli liver abscess associated with aerobilia: a case report.
AB  - Pyogenic liver abscesses are commonly caused by biliary tract infections. We
      report here a case of liver abscess developed secondary to a biliary-enteric
      fistula. A 83 year old diabetic woman was admitted because of sepsis due to
      Klebsiella pneumoniae and E. Coli and with upper right quadrant pain. Six months
      before admission, a laparoscopic cholecystectomy was performed. The abdominal
      sonography showed a liver abscess associated with an important aerobilia. The
      Magnetic Resonance Cholangiography showed a choledocho-colic fistula with an
      important inflammatory background. There was no evidence of neoplasia or
      inflammatory bowel disease. The evolution was marked by the development of
      urinary and bronchial tract infection due to Klebsiella. Septic metastasis are
      characteristics of Klebsiella liver abscesses. Percutaneous drainage associated
      with a intravenous antibiotherapy was performed.

PMID- 15462513
TI  - Atypical systemic lupus erythematosus or Castleman's disease.
AB  - Collagen vascular diseases and malignancies have common systemic and immune
      features. We report a case of a 21 year old female patient with constitutional
      symptoms, polyserositis, spontaneous rupture of the spleen, leukocytoclastic
      vasculitis and acute renal failure. The tentative diagnosis of SLE was made
      because she developed a positive antinuclear factor (1/640), with anti-SSA
      antibodies and a positive lupus anticoagulans. Two months later a cervical
      lymphadenopathy occurred while recieving treatment with prednisolone. A lymph
      node biopsy revealed morphologic features of a SLE, similar to those observed in
      multicentric Castleman's disease (MCD). MCD is a distinct type of a
      lymphoproliferative disorder of unknown etiology. The difficulties in
      differential diagnosis of these two diseases are discussed.

PMID- 15462515
TI  - [An unusual case in Belgium of intestinal myiasis due to Eristalis tenax].
AB  - We report an unusual case in Belgium of indigenous intestinal myiasis caused by
      Eristalis tenax during canicular summer 2003 in a 36 year old man living in
      Belgium. This patient complain near its general practitioner about diarrhea and
      intestinal rumbles. Larvae emitted on several occasions were identified as
      Eristalis tenax larvae. Socio-economical status of the patient and atmospheric
      conditions seems to be related to this observation. Clinical evolution has been
      spontaneously and quickly positive. An empirical treatment with an association of
      metronidazole and nifuroxazide was however prescribed.

PMID- 15462516
TI  - Occurrence of Puccinia isiacae on Phragmites australis in Saudi Arabia and its
      possibility as a biological control agent.
AB  - During the summer of 2002, symptoms of rust disease were observed for the first
      time on Phragmites australis in Saudi Arabia. Light brown lesions of regular
      shape indicating uredinia of Puccinia isiacae appeared on the leaves. The
      morphology and characteristics of the fungus were described in detail with both
      light and scanning electron microscopy. The possibility of using this fungus as a
      biological control agent was also discussed.

PMID- 15462517
TI  - Genotypic analysis of strains of mutans streptococci by pulsed-field gel
      electrophoresis.
AB  - The species and serotypes of various strains of S. mutans and S. sobrinus were
      characterized by pulsed-field gel electrophoresis after the genomic DNA from the
      various strains had been digested with five restriction enzymes (EcoR I, Xba I,
      Hind III, Sfi I and BssH II) separately. Among these restriction enzymes, BssH II
      was very useful for the characterization of species and serotypes and, in
      particular, digestion discriminated between serotypes d and g. The restriction
      patterns obtained from the genomic DNA of isolates isolated from children's
      saliva were essentially identical to those from the genomic DNA of the standard
      laboratory strains. Patterns of BssH II digests of the genomic DNA of 10 isolates
      identified as S. sobrinus were characteristic of serotype g of the standard
      laboratory strains. Our results indicate that digestion with BssH II and
      subsequence analysis by pulsed-field gel electrophoresis should be useful for the
      characterization of species and serotypes and for epidemiological studies of
      mutans streptococci.

PMID- 15462518
TI  - Characterization of the metabolite produced by Mycosphaerella pinodes, the causal
      agent of mycosphaerella blight on field peas (Pisum sativum L.).
AB  - The metabolite produced by Mycosphaerella pinodes, the causal agent of
      mycosphaerella blight on field peas, was detected by thin layer chromatography
      (TLC) and was analyzed for its chemical and pathogenic characteristics. One blue
      dot was detected using 254nm UV light on TLC plate, and a spray of rho
      anisaldehyde (110 degrees C, 30 min) also produced a blue dot. The solvent
      systems used for TLC analysis were ethyl acetate/water/acetone (5/2/5),
      chloroform/methanol/glacial acetic acid (19/10/2), toluene/ethyl acetate/90%
      formic acid (6/3/1), diethylether/methanol/water/90% formic acid (95/4/1/1), and
      bezene/methanol/acetic acid (24/2/1), with R(f) values (min-max) of 0.09-0.18,
      0.88-0.95, 0.06-0.15, 0.39-0.47 and 0.05-0.12, respectively. The recovered
      metabolite from the TLC plate displayed UV absorption peaks at 212, 244, 250, 256
      and 261 nm. The proposed formula of the main component of the metabolite was
      C16H12N3O6. The TLC-purified metabolite induced symptom of discoloration on
      detached pea leaves.

PMID- 15462519
TI  - Butachlor inhibits production and oxidation of methane in tropical rice soils
      under flooded condition.
AB  - In laboratory incubation experiments, application of a commercial formulation of
      the herbicide butachlor (N-butoxymethyl-2-chloro-2',6'-diethyl acetanilide) to
      three tropical rice soils, widely differing in their physicochemical
      characteristics, under flooded condition inhibited methane (CH4) production. The
      inhibitory effect was concentration dependent and most remarkable in the alluvial
      soil. Thus, following application of butachlor at 5, 10, 50 and 100 microg g(-1)
      soil, respectively, cumulative CH4 production in the alluvial soil was inhibited
      by 15%, 31%, 91% and 98% over unamended control. Since CH4 production was less
      pronounced in the sandy loam and acid sulfate soil, the impact of amendment with
      butchalor, albeit inhibitory, was less extensive than the alluvial soil.
      Inhibition of CH4 production in butachlor-amended alluvial soil was related to
      the prevention in the drop in redox potential as well as low methanogenic
      bacterial population especially at high concentrations of butachlor. CH4
      oxidation was also inhibited in butachlor-amended alluvial soil with the
      inhibitory effect being more prevalent under flooded condition. Inhibition in CH4
      oxidation was related to a reduction in the population of soluble methane
      monooxygenase producing methanotrophs. Results demonstrate that butachlor, a
      commonly used herbicide in rice cultivation, even at very low concentrations can
      affect CH4 production and its oxidation, thereby influencing the biogeochemical
      cycle of CH4 in flooded rice soils.

PMID- 15462520
TI  - Genetic variability and taxonomic position of ectomycorrhizal fungus Pisolithus
      from India.
AB  - Eight ectomycorrhizal fungal isolates of Pisolithus associated with Eucalyptus
      species in different parts of India were collected and the genetic variability of
      these isolates was studied by ITS-RFLP and ITS sequencing. All the isolates
      showed same RFLP patterns with each restriction enzyme, indicating all these
      isolates of Pisolithus are of the same genotype. The sequence comparison of KN6
      of Indian isolate showed high sequence similarities with the isolates of
      Pisolithus associated with Eucalyptus from Australia. Phylogeny analysis showed
      that all the isolates compared in this study clustered into four main groups The
      Indian isolate (KN6) clustered with Pisolithus albus isolates of group I, which
      are associated with Eucalyptus. These results suggested that Pisolithus isolates
      found in India are P. albus.

PMID- 15462521
TI  - Homologies among three Bacillus licheniformis plasmids and molecular
      characterization of their replication module.
AB  - To assess to what extent three Bacillus licheniformis plasmids had the same
      molecular organization a physical map of the 9.34, 8.40 and 7.90 kb plasmids was
      achieved by using seventeen restriction enzymes. Southern hybridization was
      performed on plasmids using restriction fragments of the smallest plasmid as
      probes. Data from different hybridization patterns show a close homology among
      the three plasmids hypothesizing a similar molecular organization. The lack of
      plasmid diversity observed, seem to support the hypothesis of a similar phylogeny
      among these plasmids. This investigation provides more information concerning
      phylogeny, interrelationships and level of diversity among Bacillus plasmids and
      a molecular characterization of three plasmids useful for the construction of
      cloning vectors.

PMID- 15462522
TI  - Effect of soil bradyrhizobia on the success of soybean inoculant strain CB 1809.
AB  - Four decades of soybean [Glycine max (L.) Merr.] cultivation in South Africa has
      resulted in the establishment of populations of bradyrhizobia against which the
      recently introduced inoculant strain CB 1809 must compete. Serological and DNA
      fingerprinting methods were used to study the diversity of nodule isolates from
      soils at Bergville, Koedoeskop and Morgenzon. Dominant serogroups included
      Bradyrhizobium elkanii serotype 76 at Bergville (67%), Bradyrhizobium japonicum
      serotype 123 at Morgenzon (81%) and B. japonicum serotype 135 at Koedoeskop
      (100%). Their origin is unknown as they do not correspond in serotype to strains
      used in previous inoculants. A small percentage of isolates from Bergville (13%)
      and Morgenzon (16%) were serologically homologous to strain WB 1 (serotype
      31/76), applied for two decades before CB 1809 (serotype 122). Nitrogen-fixing
      effectiveness of CB 1809 was superior to 60% of the isolates tested from
      Bergville and Morgenzon, but similar to 73% of the Koedoeskop isolates. Seed and
      liquid-in-furrow application methods increased CB 1809 nodule occupancy at least
      three-fold above background levels at Bergville (pH 5.16) and Morgenzon (pH
      6.33). Inoculation did not, however, increase CB 1809 nodule occupancy at
      Koedoeskop (pH 7.76), possibly because alkaline soil conditions favoured the
      serotype 135 population predominant at this site.

PMID- 15462523
TI  - Occurrence of Gluconacetobacter diazotrophicus in tropical and subtropical plants
      of Western Ghats, India.
AB  - Endophytic bacteria were isolated from the tissues of surface sterilized roots,
      stems, and leaves of fifty different crop plants. Phenotypic, biochemical tests
      and species-specific PCR assay permitted identification of four isolates of
      Gluconacetobacter diazotrophicus from root tissues of carrot (Daucus carota L.),
      raddish (Raphanus sativus L.), beetroot (Beta vulgaris L.) and coffee (Coffea
      arabica L.). Further the plant growth promoting traits such as nitrogenase
      activity, production of phytohormone indole acetic acid (IAA), phosphorus and
      zinc solubilization were assessed. Significant nitrogenase activity was recorded
      among the isolates and all the isolates produced IAA in the presence of
      tryptophan. Though all the four isolates efficiently solubilized phosphorus, the
      zinc solubilizing ability differed among the isolates.

PMID- 15462524
TI  - RAPD-PCR analysis of Staphylococcus aureus strains isolated from bovine and human
      hosts.
AB  - Staphylococcus aureus is one of the most important pathogens in humans and
      animals. In this study eighty strains were analyzed by RAPD-PCR to assess the
      genetic relationship between S. aureus isolates from bovine and human hosts.
      Results were compared with those obtained by biotyping. Fifty-two percent of the
      S. aureus isolates belonged to a host specific biotype (human, bovine and
      poultry). Bovine and human ecovars were the most prevalent. Dendrogram obtained
      by RAPD results showed that all the isolates clustered into eleven groups (A-K)
      at a relative genetic similarity of less than 30% when analyzed with the three
      primers. Group A clustered 95% of the human host isolates and the remaining
      groups (B-K) clustered the bovine host isolates. Principal coordinate analysis
      also showed that the isolates could be arbitrarily divided into two groups,
      bovine and human, by the second coordinate. Only 9 isolates (11%) were not
      clustered into these groups. The genetic diversity among the S. aureus isolates
      from bovine hosts is relatively low compared to that of isolates from human
      hosts. There were no statistically significant differences among isolated from
      bovine and human hosts. This study shows that RAPD-PCR assayed with three primers
      can be successfully applied to assess the genetic relationship of S. aureus
      isolates from different hosts.

PMID- 15462525
TI  - FT-IR spectroscopic characteristics of differently cultivated Bacillus subtilis.
AB  - Bacillus subtilis is an aerobic endospore forming bacterium widely spread in
      different environments. Because it represents a biological agent of some health
      relevance, its rapid detection and identification is highly desirable. By using
      FT-IR spectroscopy for this purpose slightly different characteristics were
      obtained from cell mass grown in differently composed cultural media, and
      harvested in different phases of bacterial growth. If cultivated uniformly, i.e.,
      24h at 30 degrees C in a minimum-strength nutrient broth, cell mass of B.
      subtilis delivered a well differentiated spectrum with major absorption bands of
      nucleic acid structures at 3300cm(-1), cell wall constituents at 3000-2800cm(-1),
      proteinaceous structures at 1660, 1544 and 1235cm(-1), and some aliphatic
      structural units at 1080cm(-1). Attenuated total reflectance, and
      absorption/transmission scanning techniques, delivered structurally identical
      spectra but those obtained by the former technique were more expressed.

PMID- 15462528
TI  - Rhizosheath of sinai desert plants is a potential repository for associative
      diazotrophs.
AB  - Among 42 plant species representing the flora of north Sinai, two possessed sand
      grain sheath encasing the roots. They are Panicum turgidum Forssk. and
      Stipagrostis scoparia (Trin.and Rupr.) deWinter. Rhizosheaths, compared to
      surrounding free sand, accommodated higher population density of microorganisms
      including associative diazotrophs. Isolates secured belonged to the species of
      Bacillus circulans, Paenib. macerans (Bacillus macerans), Enterobacter
      agglomerans, Agrobacterium radiobacter and Chryseomonas luteola (Pseudomonos
      luteola). The rhizosheath potentiality in re-vegetating sand dunes and arid
      lands, through nitrogen fixation, plant-water relationship and root continuity
      for nutrient uptake, are discussed.

PMID- 15462527
TI  - Comparison of PCR and culture for detection of Nocardia asteroides in brain
      specimens from experimentally infected BALB/c mice.
AB  - Systemic infection of BALB/c mice with Nocardia asteroides strain GUH-2 results
      in widespread replication of the organism in the brain, followed by its immune
      mediated clearance. The present study compared the sensitivity of polymerase
      chain reaction (PCR) to bacterial culture for detection of cerebral nocardial
      infection in this experimental system. Mice (n=4/time point) were administered N.
      asteroides by intravenous injection, and brain specimens were evaluated for
      Nocardia by PCR and culture at post-infection days 2, 7, 14 and 21. Nocardia was
      detected by PCR in all infected animals on post-infection days 2, 7, and 14, and
      in one of four mice on post-infection day 21; in contrast, the organism was
      detected by culture only on post-infection days 2 and 7. These findings suggest
      that PCR may be more sensitive than culture for the detection of low numbers of
      Nocardia in the brain.

PMID- 15462529
TI  - Antifungal activity of Tagetes patula extracts on some phytopathogenic fungi:
      ultrastructural evidence on Pythium ultimum.
AB  - Methanol extract, obtained from Tagetes patula plant, was assayed against three
      phytopathogenic fungi: Botrytis cinerea, Fusarium moniliforme and Pythium
      ultimum. The antifungal activity was tested both in the dark and in the light,
      using two different lighting systems. The data showed that the extract proved to
      have a dose-dependent activity on all the fungi with a marked difference between
      treatments in the light than in the dark. Good growth inhibition was observed in
      fungi only when these were treated with the highest dose of the extract and
      irradiated, whereas the same dose gave only a modest inhibition when the
      experiment was conducted in the dark. At 5 and 10 microg/ml in the dark, growth
      increased. The results indicated that the presence of a luminous source enhances
      the antifungal activity, with small differences between UV-A and solar spectrum
      light. SEM and TEM observations on Pythium ultimum revealed that the Tagetes
      patula extract induced alterations on cell fungal membranes with a
      photoactivation mechanism possibly involving the production of free radicals and
      leading to a premature aging of the mycelium.

PMID- 15462530
TI  - Purification and biochemical characterization of polygalacturonase II produced in
      semi-solid medium by a strain of Fusarium moniliforme.
AB  - A strain of Fusarium moniliforme isolated from a tropical mangrove ecosystem near
      Mumbai, India and deposited in the National Collection of Industrial
      Microorganisms (NCIM) as F. moniliforme NCIM 1276. The organism produced a single
      extracellular polygalacturonase (PG I) [EC 3.2.1.15] at pH 5 and a single pectate
      lyase (PL) [EC 4.2.2.2] at pH 8 in liquid medium containing 1% citrus pectin.
      Growth on semi-solid medium containing wheat bran and orange pulp resulted in a
      three-fold increase in PG production and a two-fold increase in PL production in
      comparison with that in liquid medium. The increased production of PG on semi
      solid media, as compared to production in liquid media was investigated. The
      increased production of PG was partly due to the expression of a second
      polygalacturonase (PG II) isoenzyme by the fungus which was biochemically
      different from the one produced in liquid medium. The second PG II was a 30.6kDa
      enzyme, had an alkaline pI of 8.6, the Km was 0.166mg ml(-1), Vmax 13.33 micromol
      min(-1) mg(-1) and the kcat was 403 min(-1). It had a specific activity of 18.66U
      mg(-1). The differences between the PGs (PG I and PG II) suggest that the two
      enzymes are the products of different genes. The fungus also produced the same
      two PGs when it infected Lycopersicon esculentum (tomato). Only one PL was
      produced irrespective of growth conditions.

PMID- 15462531
TI  - Effects of active sunscreen ingredient combinations on the topical penetration of
      the herbicide 2,4-dichlorophenoxyacetic acid.
AB  - Sunscreen use can reduce the incidence of certain skin cancers. However, a number
      of commercially available formulations have been shown to enhance the transdermal
      penetration of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). Most of the
      active ingredients used in these compounds can individually act as penetration
      enhancers. Commercial sunscreens frequently contain multiple active ingredients
      in order to provide broad sunscreen protection. The purpose of this study was
      therefore to examine the effect of these active ingredient combinations on the
      transdermal absorption of 2,4-D in vitro. All six of the combinations tested
      resulted in increased cumulative penetration (P <0.01) and faster lag times (P
      <0.05). The 2,4-D cumulative penetration in the presence of the OFF! Deepwoods
      combination was significantly greater than the absorption with either the
      individual ingredients or their average (P <0.05). A systematic study designed to
      isolate the chemicals responsible for this enhancement demonstrated that with UV
      absorbers DEET synergistically increased the 2,4-D penetration and that DEET's
      cumulative enhancement properties correlate with its concentration. By contrast,
      octocrylene significantly slowed the lag time when used in combinations and was
      the only active ingredient that showed any antagonistic effects on 2,4-D
      penetration. Because none of the active ingredient combinations were able to
      inhibit dermal uptake of 2,4-D, it seems that proper selection of inert
      ingredients may be the most feasible solution for reducing penetration
      enhancement.

PMID- 15462532
TI  - Sunscreens containing physical UV blockers can increase transdermal absorption of
      pesticides.
AB  - People are encouraged to wear sunscreens because of their effectiveness at
      reducing the risk of skin cancer. The dermal penetration of the herbicide 2,4-D
      can be enhanced by commercial formulations containing chemical ultraviolet (UV)
      absorbers, the absorbers themselves and the insect repellent DEET. This work has
      been extended to determine whether commercially available sunscreens containing
      the physical UV absorbers titanium dioxide (TiO2) or zinc oxide (ZnO) enhance the
      transdermal absorption of pesticides. Hairless mouse skin was pretreated with
      either commercially available sunscreens or the UV absorbers themselves,
      dissolved in phenyl trimethicone. In vitro permeability studies were performed
      with the pesticides 2,4-D, paraquat, parathion or malathion. The data demonstrate
      that pretreatment with five of the nine sunscreens tested increased the
      transdermal absorption of 2,4-D (P<0.05). Transdermal studies using paraquat,
      parathion and malathion pretreated with a representative sunscreen all
      demonstrated significant penetration enhancement when compared to controls
      (P<0.05). Repeated 2,4-D and sunscreen applications resulted in either no change
      between pulses or an increase in absorption after the second pulse depending on
      the washing regimen. Examining penetration of individual UV absorbers formulated
      in phenyl trimethicone showed that that ZnO can impede 2,4-D penetration and TiO2
      had no effect. Combining UV absorbers in the presence of trimethicone resulted in
      'sunscreens' that could actually inhibit 2,4-D penetration. Inert ingredients
      therefore control the increased absorption seen in commercial sunscreen products
      and this enhancement can be eliminated by substituting phenyl trimethicone as the
      solvent. Sunscreen use must still be encouraged even with the undesirable side
      effect of increased penetration through the skin.

PMID- 15462533
TI  - Effect of haemoperfusion on plasma paraquat concentration in vitro and in vivo.
AB  - This study was to observe the paraquat (PQ) reduction rate after haemoperfusion
      (HP) on the groups of a relatively large number: 50 survivors out of 105 patients
      with acute PQ poisoning. We started off by measuring the clearance of
      haemodialysis (HD) and HP for the PQ in vitro. At the blood flow of 250 mL/min,
      the PQ clearance was greater in HP than in HD during the first 90 minutes: 215
      versus 175 mL/min at 30 minutes, 213 versus 201 mL/min at 60 minutes, and 199
      versus 179 mL/min at 90 minutes. The clearance in HP decreased rapidly after two
      hours. By the end of the dialysis, however, the final concentration in container
      decreased to 5.7 microg/mL in HD and 1.5 microg/mL in HP, which implied that
      although HD was cleared more effectively during the later stages, the overall
      elimination was greater in HP. Following this preliminary investigation, we
      performed HP on all the patients in order to assess the extracorporeal
      elimination. One hundred and five patients who had swallowed one to three
      mouthfuls of PQ (24.5% w/v) solution were subjected to the in vivo study. The
      reduction rate of PQ was checked out by measuring the PQ concentration in plasma
      before and after four hours of HP. Seeing the reduction rate was significantly
      higher in the survivors group than in the nonsurvivors group (80.3+/-19.9 versus
      67.2+/-19.2%, P <0.01), we concluded that adequate HP appears to be an
      indispensable treatment for patients with acute PQ poisoning.

PMID- 15462534
TI  - The concentration, dry deposition, composition study of ambient air particulate
      and metallic pollutants at a traffic sampling site.
AB  - Aerosol samples were collected by total suspended particulate (TSP) and dry
      deposition plate (downward, upward) from August to November in 2003 in central
      Taiwan. The particulate metallic elements (Fe, Pb, Zn, Cu, Mg and Mn) were also
      measured in this study during the summer and autumn periods of 2003. The results
      obtained in this study indicated that the ambient air particulate mass
      concentrations in the daytime period (averaged 975.4 microg/m3) were higher than
      the night-time period (averaged 542.1 microg/m3). And the downward dry deposition
      fluxes (averaged 58.12 microg/m2-sec) were about 2.2 times that of upward dry
      deposition fluxes (averaged 26.37 microg/m2-sec) in the daytime period.
      Furthermore, the average downward dry deposition fluxes (averaged 26.54 microg/m2
      sec) were also about 2.3 times that of upward dry deposition fluxes (averaged
      11.52 microg/m2-sec) in the night-time period. Moreover, the average downward dry
      deposition fluxes are greater than the upward dry deposition fluxes for all the
      heavy metals in either daytime or night-time period. In addition, the deposition
      velocity for mass, metallic elements (Fe, Pb, Zn, Cu, Mg and Mn) during daytime
      and night-time period were also calculated. In addition, the average TSP
      composition (mg/g) in the daytime period of the metallic elements (Fe, Pb, Zn,
      Cu, Mg and Mn) is 1.73, 0.26, 1.16, 0.28, 0.43 and 0.12 mg/g, respectively. And
      the average TSP composition in the night-time period of the metallic elements
      (Fe, Pb, Zn, Cu, Mg and Mn) is 3.02, 0.33, 1.57, 0.41, 0.58 and 0.13 mg/g,
      respectively at traffic sampling site of central Taiwan.

PMID- 15462526
TI  - Molecular identification of yeasts from soils of the alluvial forest national
      park along the river Danube downstream of Vienna, Austria ("Nationalpark
      Donauauen").
AB  - We analysed the diversity of yeasts from different soils in a river-floodplain
      landscape at the river Danube downstream of Vienna, Austria ("Nationalpark
      Donauauen"). 136 strains were isolated, identification of species was done with
      molecular methods. Partial sequencing of the 26S rRNA gene resulted in 36
      different sequences, they could be assigned to 16 genera, apart from two sequence
      types (from three isolates), which were not clearly assigned to any genus. 18
      species were identified and confirmed by means of PCR fingerprinting. The most
      frequently isolated genus was Cryptococcus (61 isolates and 12 sequence types).
      Basidiomycetes dominated with about 60% above the members of the Ascomycetes.
      About half the yeasts was isolated from the litter, the quantity decreased with
      soil depth.

PMID- 15462535
TI  - Postdisaster PTSD over four waves of a panel study of Mexico's 1999 flood.
AB  - Samples of adults representative of Tezuitlan, Puebla and Villahermosa, Tobasco
      (combined N = 561), were interviewed 6, 12, 18, and 24 months after the
      devastating 1999 floods and mudslides in Mexico. Current DSM-IV PTSD and major
      depressive disorder (MDD) were assessed with the Composite International
      Diagnostic Interview. At Wave 1, PTSD was highly prevalent (24% combined),
      especially in Tezuitlan (46%), which had experienced mass casualties and
      displacement. Both linear and quadratic effects of time emerged, as PTSD symptoms
      initially declined but subsequently stabilized. Differences between cities
      lessened as time passed. Comorbidity between PTSD and MDD was substantial. The
      findings demonstrate that the international health community needs to be prepared
      for epidemics of PTSD when disasters strike developing areas of the world.

PMID- 15462536
TI  - PTSD symptoms, demographic characteristics, and functional status among veterans
      treated in VA primary care clinics.
AB  - We hypothesized that PTSD symptomatology would have an inverse relationship with
      functional status and would vary as a function of sociodemographic variables.
      Primary care patients (N = 513) at two VA Medical Centers were randomly selected
      and recruited to participate. After adjustment for other demographic variables,
      PTSD symptom levels were significantly related to age (younger patients had more
      severe symptoms), employment status (disabled persons had higher symptom levels),
      war zone experience, and clinic location. PTSD symptomatology was inversely
      related to mental and physical functioning, even after control for potential
      confounding. These findings have implications for screening and service delivery
      in VA primary care clinics, and support the more general finding in the
      literature that PTSD is associated with impaired functioning.

PMID- 15462537
TI  - A mediational model of PTSD in World War II veterans exposed to mustard gas.
AB  - Structural equation modeling (SEM) was used to examine associations among trauma
      related contextual factors, initial psychological reactions, social support, and
      subsequent disclosure on posttraumatic stress disorder (PTSD) symptoms in a
      sample of World War II (WWII) veterans exposed to mustard gas (N = 305). A
      structural model suggested that initial psychological reaction mediated the
      relationship between variables related to the context of mustard gas exposure and
      severity of PTSD symptoms 50 years later. Unexpectedly, social support appeared
      to be positively related to PTSD symptoms, and not related to the contextual
      variables or initial psychological reactions. These findings contribute to our
      understanding of PTSD in older veterans, and have relevance for early
      intervention services to prevent PTSD among those at risk for exposure to toxic
      agents.

PMID- 15462538
TI  - Posttraumatic stress disorder symptoms and parenting satisfaction among a
      national sample of male vietnam veterans.
AB  - This study examined relationships between posttraumatic stress disorder (PTSD)
      symptoms and parenting satisfaction. Total PTSD severity scores and avoidance and
      emotional numbing symptoms were significantly associated with parenting
      satisfaction. These associations remained significant even after controlling for
      partner violence, major depression, and alcohol abuse/dependence. Results suggest
      that higher levels of PTSD symptoms and avoidance and emotional numbing symptoms
      in particular may have a deleterious effect on parent-child relationship
      satisfaction.

PMID- 15462539
TI  - Evaluation of initial posttrauma cardiovascular levels in association with acute
      PTSD symptoms following a serious motor vehicle accident.
AB  - The present study examined the relationship between heart rate (HR) and blood
      pressure (BP) levels assessed at multiple time points posttrauma and subsequent
      acute posttraumatic stress disorder (PTSD) symptoms present at a 1-month follow
      up. HR and BP levels were measured in 65 motor vehicle accident (MVA) survivors
      during Emergency Medical Service transport, upon admission to the trauma unit,
      for the first 20 min postadmission and on the day of discharge. Hierarchical
      linear modeling analyses revealed no significant relationships between
      cardiovascular levels and acute PTSD symptoms. Given the small sample size, these
      results should be interpreted with caution. However, the present results question
      the use of initial cardiovascular levels as predictors of subsequent acute PTSD
      in seriously injured MVA victims.

PMID- 15462540
TI  - Changes in mothers' basic beliefs following a child's bone marrow
      transplantation: the role of prior trauma and negative life events.
AB  - This longitudinal study examined the relation between life stress and basic
      beliefs about self-worth and the benevolence and meaningfulness of the world
      among mothers of children undergoing bone marrow transplantation (BMT). One
      hundred mothers completed study measures during the child's hospitalization for
      BMT and 1 year later. Prior trauma and recent negative events were associated
      with basic beliefs during hospitalization and also with changes in basic beliefs
      in the subsequent year, with distress mediating some of these relations. Findings
      also demonstrated relations between basic beliefs and physical and mental
      functioning. However, each basic belief exhibited different relations with study
      variables, suggesting the need to investigate them separately.

PMID- 15462541
TI  - Posttraumatic growth in child survivors of a road traffic accident.
AB  - Although the negative consequences of trauma have been well researched and
      described, posttraumatic growth has only recently come to the attention of
      researchers. This paper considers whether children (aged 7-18 years) who have
      been involved in a road traffic accident can experience posttraumatic growth
      outcomes. From 158 children who took part in an interview, qualitative analysis
      of interview notes found that 67 (42%) reported some aspect of posttraumatic
      growth, most notably in terms of their philosophy of life. Of these, 25 (37%)
      were also assessed as experiencing posttraumatic stress disorder.

PMID- 15462542
TI  - Cognitive-Behavioral Couple's Treatment for posttraumatic stress disorder:
      initial findings.
AB  - This pilot study was an initial investigation of Cognitive-Behavioral Couple's
      Treatment (CBCT) for posttraumatic stress disorder (PTSD). Seven couples in which
      the husband was diagnosed with PTSD secondary to Vietnam combat experiences
      completed the treatment. According to independent clinician assessment and
      partner report, the veterans had substantial improvements in their PTSD symptoms.
      The veterans reported less dramatic improvements in their PTSD symptoms, but
      endorsed significant improvements in their depression and anxiety. The partners
      reported improved relationship satisfaction, whereas the veterans' relationship
      satisfaction was unchanged across treatment. The current findings are compared
      with findings on other forms of empirically validated treatment for PTSD and
      previous studies of CBCT for various individual problems. Theoretical
      implications and future directions are offered.

PMID- 15462543
TI  - Social acknowledgment as a victim or survivor: a scale to measure a recovery
      factor of PTSD.
AB  - The development and validation of a new measure of social acknowledgment as a
      victim or survivor is presented, whose items were derived from previous research
      on social recovery factors of post-traumatic stress disorder. The Social
      Acknowledgment Questionnaire (SAQ) was administered to nontreatment seeking
      traumatized persons--178 former political prisoners in East Germany and 151
      recently traumatized interpersonal crime victims. Principal components analysis
      yielded three factors--Recognition as victim, General disapproval, and Family
      disapproval. The factors showed high internal consistency and good test-retest
      reliability; correlated moderately to strong with measures of PTSD severity,
      social support, and reluctance to talk about the trauma. In comparison to a
      conventional measure of social support, the SAQ predicted comparably better
      between persons with high- and low-PTSD severity.

PMID- 15462544
TI  - Are reports of posttraumatic growth positively biased?
AB  - This study examines positivity bias in reports of growth following exposure to
      traumatic events. Participants (N = 276) from an urban university and a superior
      court jury pool were randomly assigned to one of two methodological groups. In
      one, participants responded to the Posttraumatic Growth Inventory (PTGI) in
      relation to a specific stressful event. In the other, PTGI questions were not
      linked to specific events. Findings indicate that current methods for assessing
      posttraumatic growth (PTG) may actually underestimate growth. That is, linking
      questions about growth to specific stressors may have led participants to be
      cautious about attributing their growth experiences to a traumatic event. These
      findings contradict notions that current methods of measuring PTG create a
      positivity bias. Suggestions for future research include the use of prospective
      designs and corroborating reports of growth.

PMID- 15462545
TI  - [Attitudes and hierarchy of medical values in a gynecology and obstetrics
      department].
AB  - BACKGROUND: The current practice of medicine is suffering a deep crisis of values
      due to the process of super-specialization, marketing tendencies, growing and the
      practice of a defensive medicine. OBJECTIVE: To examine the attitudes and
      hierarchy of medical values in undergraduate students, residents and faculty
      physicians in an obstetrics and gynecology department. MATERIAL AND METHODS: A
      descriptive, open, observational and transversal study was done, in which a
      questionnaire including a demographic data-record and 22 questions related to
      values and attitudes was applied to 29 individuals belonging to the medical staff
      of the gynecology and obstetrics service at Hospital General Dr. Manuel Gea
      Gonzalez. RESULTS: Medical knowledge, honesty and respect were consistently
      mentioned as the most emphasized characteristics across the examination.
      Benevolence and compassion were frequently indicated in undergraduate students,
      but not in third year residents and specialists. Respect for the right of
      individual patients to make their own choices about their health care, in some
      doctors, is a problematic issue. CONCLUSIONS: The teaching of professionalism is
      important in residency training and is expected to be an equal partner in the
      triad of knowledge, skills and values.

PMID- 15462547
TI  - [Current criterion for diagnosing polycystic ovary syndrome].
AB  - The current consensus on diagnostic criteria of polycystic ovary syndrome has
      concluded that it is a syndrome of ovarian dysfunction along with
      hyperandrogenism and morphology of polycystic ovary. The clinical manifestations
      may include irregular menses, androgen excess, and obesity, but insulin
      resistance is also a common feature. There is an increased risk of type 2
      diabetes mellitus. Treatment of polycystic ovary includes ovulation induction,
      amelioration of androgen signs and correction of insulin resistance.

PMID- 15462546
TI  - [Comparison of the evolution of women with cervical intraepithelial neoplasia
      degree III treated with cervical cone: negative vs positive surgical margin].
AB  - BACKGROUND: Incidence of positive surgical margins in patients submitted to
      conization is 25%. OBJECTIVE: To know the clinical evolution of women with
      cervical high grade squamous intraepithelial lesion subjected to surgical
      handling with cervical cone, and expectant handling, comparing positive margins,
      with negative margins. MATERIAL AND METHODS: We included women subjected to
      conization for high grade squamous intraepithelial lesion and subsequent
      expectant handling, in a period of five year. They were included in two groups:
      I. Patients with negative margins and II. Patients with positive margins. Cure
      approaches settled down with two cytologic-colposcopic negative controls;
      persistence, when the first control was positive and recurrence, when some
      appeared positive after two negatives. It was used binomial analysis and square
      Chi. RESULTS: Forty-seven women were studied with conization; 10 of positive
      margins and 37 of negative. In the group with positive margins there were eight
      cures (80%) and two recurrences (20%); while in the group of negative margins
      there were 35 cures (94%) and two recurrences (6%). There was not significant
      difference in both groups (p > 0.05). CONCLUSIONS: The expectant handling is a
      good alternative in patients subjected to conization with positive margins, since
      it is high the percentage of spontaneous regression of the lesion.

PMID- 15462548
TI  - [Painful acute syndrome due to functional tumors of the ovary. 1949].

PMID- 15462549
TI  - [General recommendations for improving the obstetric care quality].

PMID- 15462550
TI  - A new era of oral health promotion for special needs dentistry.

PMID- 15462551
TI  - Priorities for oral health goals in a sample of older adults.
AB  - This study was conducted to identify oral health factors that are important to
      people who are elderly. By identifying factors valued by patients who are older,
      dental professionals can gain better insights into the preferences and priorities
      that patients use in making dental treatment decisions. To determine which
      factors are important to this population, we compiled a list of oral health goals
      identified through a literature review. To supplement this initial list, we
      undertook line-by-line (open) coding of transcripts of two sets of semi
      structured interviews. The first set of interviews explored the decision of older
      adults to seek treatment in response tooth pain. The second set of interviews
      elicited anticipated responses to three scenarios involving extensive restoration
      and one scenario involving extraction and prosthetic replacement among older
      patients at a dental school.

PMID- 15462552
TI  - Dental characteristics of the Wolf-Hirschhorn syndrome: a case report.
AB  - Little attention in the dental literature has been given to the dental
      characteristics of patients with the Wolf-Hirschhorn Syndrome (WHS). The syndrome
      is caused by deletions of the terminal portion of the short arm of chromosome 4.
      This case report provides information on dental anomalies noted in a child with
      WHS. The dental findings include agenesis of multiple permanent teeth,
      particularly premolars and molars, taurodontism, and over-retained primary teeth.
      This syndrome exhibits variable clinical expressivity, possibly due to the extent
      and the specific locus of the chromosomal deletion. Further studies are required
      to obtain a clearer view of the clinical oral/dental manifestations of this
      syndrome.

PMID- 15462553
TI  - Use of cryotherapy to enhance mouth opening in patients with cerebral palsy.
AB  - This study was conducted to assess the effect of cryotherapy on masseter
      spasticity on mouth opening, which is required for oral hygiene and dental
      treatment. The inter-incisal distance was measured before cryotherapy in 24
      patients with cerebral palsy who had spasticity of the tetraparesis type. Ice was
      then applied on the skin surface with sliding movements over the masseter,
      bilaterally for one minute. Inter-incisal distance was then measured again. The
      results showed a significant increase of the inter-incisal distance after the
      application of cold to the masseter. We conclude that the action of cryotherapy
      on the masseter muscle produced a temporary reduction of spasticity, facilitating
      access to the occlusal and palatal surfaces of the maxillary molars. This
      improved access can be useful during dental treatment as well as preventive
      dental care such as oral hygiene.

PMID- 15462554
TI  - Treatment of muscle spasticity in patients with cerebral palsy using BTX-A: a
      pilot study.
AB  - This study was designed to verify the safety and efficacy of botulinum toxin type
      A (BTX-A) used as a neuromuscular block on spastic masticatory musculature of
      children with cerebral palsy. Six patients who had spastic-tetraplegic cerebral
      palsy, aged 5 to 20 years were selected. All patients had spasticity of the jaw
      muscles, bruxism, lower lip trauma, limited mouth opening, and difficulties in
      cleaning the oral cavity. The patients were sedated under general anesthesia,
      while the dentist injected the masseter and temporalis muscles bilaterally with
      150 and 75 units of BTX-A each. Clinical examinations were conducted at 7, 14,
      30, and 90 days after the initial appointment. We found statistically significant
      decreases in muscle spasticity and bruxism (p = 0.002), improved inter-incisal
      opening (p = 0.002), improved oral hygiene (p = 0.031), and less lower lip trauma
      (p = 0.060) after the neuromuscular blocking.

PMID- 15462555
TI  - How I spent my summer vacation.

PMID- 15462556
TI  - A constant presence: the volunteer dental clinics of Minnesota.

PMID- 15462558
TI  - Tobacco cessation program: resources to help organize a dental office program.
AB  - When dentists and dental office team members assist their patients in becoming
      tobacco free, they are eliminating causative/contributing factors for a number of
      oral conditions, including cancer and periodontal diseases. These tobacco
      cessation services, when successful, can also improve the outcome of dental
      treatment and at the same time add quality and years to patients' lives. Dental
      offices that would like to provide and document tobacco cessation services will
      find the University of Minnesota School of Dentistry web site www.umn.edu/
      perio/tobacco a useful resource. For some tobacco-using patients who are
      interested in quitting, our Individual Counseling Clinic at (612) 626-0440 is a
      possible option, and referrals are welcome. For further information, please
      contact Dr. Stafne at stafn001@umn.edu.

PMID- 15462559
TI  - Almost 44,000 children with disabilities in Minnesota.

PMID- 15462557
TI  - New initiatives in the diagnosis and prevention of oral cancer.

PMID- 15462560
TI  - What's a dentist to do?

PMID- 15462561
TI  - "The proof is in the pudding".

PMID- 15462562
TI  - Minnesota's Programs 2004 for Allied Dental Education.

PMID- 15462563
TI  - Histomorphological and quantitative immunohistochemical changes in the rat
      pancreas during aging.
AB  - Although the endocrine pancreas is the purpose of several deep investigations,
      morphological data referred to the effect of aging on the gland are not
      homogeneous. The purpose of the current work was to analyze the changes occurring
      in the pancreas of aged rats, with especial reference to the islet cell
      populations. Six young (Y), old (O) and senescent (S) male Sprague-Dawley rats
      were used. The pancreas tails were processed for light microscopy and studied by
      means of routine stains as well as by immunohistochemical identification of
      insulin-, glucagon-, somatostatin-, and pancreatic polypeptide- secreting cells
      (Dako Envision System, DAB as chromogen). A progressive pancreatic
      histoarchitecture distortion was found among the aged animals. Even when the
      alterations were not uniformly observed, they appeared more evident and severe in
      the S group. The S rats showed significantly increased volume density and cell
      density of the B cell population, as well as larger number of islet profiles,
      when compared to O rats. A significant progressive increment of adipose tissue
      was also evident in aged animals. No abnormal changes were detected in the non-B
      cell populations of the different groups. The quantitative changes found in aged
      animals suggest a possible compensatory reaction of the B cell population in an
      attempt to curb the influence of diabetogenic factors mounting with advanced age.

PMID- 15462564
TI  - Study of the myenteric and submucous plexuses after BAC treatment in the
      intestine of rats.
AB  - A morphological and quantitative study in the ileal and colonic myenteric and
      submucous plexuses of rats after BAC denervation was performed. Four groups were
      employed: SI--ileum control; CBI--denervated ileum; SC--colon control; and CBC-
      denervated colon. We used the Myosin-V immunohistochemistry technique to study
      the myenteric and submucous plexuses. In the submucous plexus of the ileum and
      colon there was not a significant decrease in the number of neurons/mm2 and of
      ganglia/mm2. The denervation of the myenteric plexus in the group CBI was 44.7%
      and in the group CBC, 68.3%. In the myenteric plexus there was also a significant
      decrease in the number of ganglia/mm2 (13.8% in group CBI and 52.14% in group
      CBC) and in the number of neurons/ganglion (33.9% in group CBI and 39.6% in group
      CBC). The morphological analyses showed that there was an alteration in the shape
      of the ganglia of the ileal and colonic myenteric plexus. The area of the cell
      bodies had a significant increase both in the myenteric and the submucous plexus
      in groups CBI and CBC. These data demonstrate that the BAC treatment causes
      morphologic and quantitative changes in the myenteric plexus and quantitative
      changes in the cell body area of the submucous plexus.

PMID- 15462566
TI  - Fine-structural details of the photoreceptor membranes in the ocellus of the
      scale-insect parasite Centrodora sp. (Hymenoptera; Aphenelidae): a case of gene
      transfer between host and parasite?
AB  - Only one insect (the scale insect Eriococcus sp.) is known, in which
      photoreceptive lamellae appear to have replaced the usual arthropod rhabdom
      microvilli. We are now reporting the presence of photoreceptive membranes, which
      also appear to resemble lamellae rather than microvilli, but they are in the
      ocellus of the tiny wasp Centrodora sp., which parasitizes scale insect eggs. The
      apparently optically homogenous lens of the Centrodora ocellus measures
      approximately 10 microm in diameter and, thus, operates at the limits of
      diffraction. We calculated that the lens is capable of focusing a parallel bundle
      of rays on the retina of the ocellus.

PMID- 15462565
TI  - Probiotics enhance the recovery of gut atrophy in experimental malnutrition.
AB  - AIM: The aim of this study was to evaluate the effect of probiotics on the
      recovery of the bowel atrophy induced by malnutrition in rats. METHODS: Twenty
      and-six Wistar rats (200-250g) were fed with either a normoproteic (sham group,
      n=6) or a free-protein diet (n=20) during 12 days. Twelve malnourished rats were
      randomized to recover during 15 days with either a hydrolyzed diet (control
      group, n=6) or the same diet enriched with probiotics (Streptococcus thermophilus
      and Lactobacillus helveticus; probiotic group, n=6). RESULTS: Probiotic group
      showed similar gain of body, liver and bowel weight than controls. At the
      jejunum, both the villus height (383+/-49 vs. 321+/-46mm; p=0.04) and crypt depth
      (157+/-31 vs. 125+/-10mm; p=0.04) were greater in probiotic group than in
      controls. The crypt depth at the cecum (214+/-22 vs. 169+/-43 mm; p=0.05) and the
      wall width at both the cecum (410+/-18 vs. 340+/-61 mm; p=0.02) and sigmoid
      (479+/-130 vs. 330+/-62 mm; p=0.03) were higher in probiotic than in control
      group. CONCLUSION: Streptococcus thermophilus and Lactobacillus helveticus
      enhance the recovery of gut atrophy induced by malnutrition. Probiotics can be
      useful as oral adjuvants during the recovery of malnutrition.

PMID- 15462568
TI  - Ultrastructure of the Lyonet's glands in larvae of Diatraea saccharalis Fabricius
      (Lepidoptera: Pyralidae).
AB  - The Lyonet's gland is found in Lepidoptera larvae, close to the excretory duct of
      the silk gland. The role played by this gland is still uncertain. This work aims
      to describe the ultrastructure of the Lyonet's gland in Diatraea saccharalis
      larvae, offering suggestions regarding its possible function. The insects were
      reared under laboratory-controlled conditions. The glands were conventionally
      prepared for transmission (TEM) and scanning (SEM) electron microscopy. SEM
      showed that Lyonet's glands are paired small structures located in the ventral
      side of the head. They are composed by clustered long cells resembling leaves.
      Under TEM observations, each cell is surrounded by a thin basal lamina and
      contains large stellate nucleus. The cytoplasm presents large and empty
      canaliculi with small microvilli. The basal plasma membrane forms numerous
      infoldings where numerous and well-developed mitochondria are concentrated. The
      cytoplasmic membrane system is poorly developed. Our ultrastructural results
      suggest that the Lyonet's gland in D. saccharalis larvae may be involved in the
      uptake of small molecules from the hemolymph; no morphological evidences of
      macromolecules synthesis and secretion were noticed. The detection of nerve
      fibers in the gland suggest a neural control for the glandular cell function.

PMID- 15462567
TI  - Intrahost distribution and transmission of a new species of cyclopoid copepod
      endosymbiotic to a freshwater snail, Pomacea canaliculata (Caenogastropoda,
      Ampullariidae), from Argentina.
AB  - A new species of cyclopoid copepod, Ozmana huarpium, is described as a symbiont
      to Pomacea canaliculata (Lamarck 1822) (Caenogastropoda, Ampullariidae). Rather
      large numbers (about one hundred copepods per snail) were found, although there
      was no evidence of harm to the host. To our knowledge, O. haemophila (symbiont to
      P. maculata), and the currently described species, O. huarpium, are the only
      copepod species ever recorded as endosymbionts to freshwater invertebrates. While
      O. haemophila is restricted to the haemocoel of its host, O. huarpium predominate
      in the penis sheath, the ctenidium and the mantle cavity, figuring in these
      pallial organs 63-65% of total mature forms. The sex ratio of the symbiont is
      skewed to the female side in these organs, specially in male hosts. The
      hypothesis that a special female tropism for the male host's pallial organs might
      ensure interindividual transmission of the symbiont was tested, with indications
      that the symbiont is mainly transmitted during copulation.

PMID- 15462569
TI  - Roadblocks along the way.

PMID- 15462570
TI  - Immunization issues in the 21st Century, part II.

PMID- 15462571
TI  - A 6-week-old girl with Group B streptococcal meningitis.

PMID- 15462572
TI  - Vaccine shortages eliminate possibility for excess capacity in stockpiles.
AB  - The ability to provide vaccines to the entire population stands as one of the
      greatest achievements of the past century. Many new antigens have been developed,
      and now more antigens are offered as part of combination vaccines, reducing the
      number of injections. Vaccines that are routinely administered protect against 11
      common childhood diseases. In addition, through herd immunity, immunization even
      offers some benefit to those who are not immunized. Providing additional
      protection has come at some additional cost, however. Immunizing a child with the
      20 doses of recommended vaccines increased in price from 200 dollars to 400
      dollars, (at the discounted government price) between 1997 and 2001. In spite of
      this impressive record, vaccines shortages have occurred for eight of the
      routinely recommended vaccines, and the conjugate pneumococcal vaccine is still
      in short supply, mandating deferral of doses three and four. These shortages have
      resulted in some harm to the system. Several temporary changes to recommendations
      were made, and it is not at all clear to what extent children for whom doses were
      deferred have been called back. School immunization requirements have been
      modified in 48% of states. Concern has been raised that we may see a reversal in
      the trend toward improved vaccine coverage, and the possibility of outbreaks is
      seen as very real. Some, but not all, of the immediate factors that led to the
      vaccine shortages of 2 years ago have been resolved. Longstanding factors that
      contributed to the shortages remain. Undervaluation by society, inadequate
      communication between involved parties, attrition of manufacturers, and the
      threat of frivolous litigation have not been addressed and may once again
      threaten the vaccine supply. Currently, four manufacturers are responsible for
      almost all of the routinely recommended vaccines used in this country. Five
      vaccines are produced by a single manufacturer. Only one vaccine, conjugate
      Haemophilus influenzae type b, is produced by three. It will take between 4 and 5
      years to improve vaccine stockpiles to the desired levels. With fewer
      manufacturers, there is no possibility for "excess" capacity that may provide a
      cushion to augment stockpiles or address any unanticipated shortfalls in supply.
      In short, the potential for additional shortages remains substantial, and the
      ability to respond to shortages may actually have worsened. We must hope the
      return of widespread shortages or even outbreaks will not be necessary before
      real solutions are implemented.

PMID- 15462573
TI  - Live viral vaccines in the control of highly infectious diseases: measles and
      varicella.
AB  - It is possible that by the end of this decade, measles and varicella two of the
      most infections and previously universal diseases of children, with massive
      levels of morbidity and significant mortality, may become of historical interest
      only. To accomplish this success, it is imperative that all involved parties do
      what is required. The vaccine supply must be assured, parents must be
      appropriately educated and reinforced by the media to bring their children to be
      immunized, and healthcare personnel must both aggressively ascertain and
      administer needed immunizations.

PMID- 15462574
TI  - Rates of Neisseria meningitidis increasing in young adults.
AB  - The burden of meningococcal disease has remained unchanged in the United States
      for the past 4 decades. The currently available meningococcal vaccine is safe and
      effective, however, due to immunogenic limitations inherent to polysaccharide
      vaccines, it has been available only for high-risk populations older than 2.
      Incorporation of a more immunogenic and effective conjugated vaccine into the
      routine immunization schedule offers an opportunity to substantially affect the
      incidence of meningococcal disease. The routine use of a meningococcal conjugate
      vaccine in the United States will save lives and prevent significant morbidity in
      children and young adults.

PMID- 15462575
TI  - The role of the Vaccine Adverse Event Reporting system (VAERS) in monitoring
      vaccine safety.
AB  - The role of the health professional in supporting the national passive
      surveillance system is essential, as the first hint of a potential problem
      usually originates with the astute clinician who reports a case to the
      appropriate source. The investigation that resulted in the voluntary withdrawal
      of rotavirus vaccine was triggered by nine reports to VAERS of intussuception,
      eight of which had occurred within 1 week of the first dose of this vaccine.
      Health professionals have access to the most complete information related to
      adverse events experienced by their patients. Any index of suspicion that a
      serious event or death may be related to vaccination is reason for the health
      professional to submit a VAERS report. Determination of whether an event was
      caused by the vaccine is not a prerequisite for filing a VAERS report. When in
      doubt, providers should report to VAERS. VAERS solicits reports for all events
      temporally related to vaccination, some of which may be coincidental and some of
      which may merely indicate a change in the frequency of expected events. Post
      marketing surveillance relies on health professionals to report suspicious
      events, thus improving the quality of reported data and contributing
      significantly to safeguarding public health. Recommendations for healthcare
      professionals to report to VAERS recently have been incorporated into the
      Standards for Pediatric Immunization Practices, which are endorsed by multiple
      professional organizations. Despite the limitations of spontaneous reports, VAERS
      provides vital information of clinical importance. The identification of signals
      in adverse event surveillance may initiate further investigation of potential
      problems in vaccine safety or efficacy, and facilitate subsequent dissemination
      of safety-related information to the scientific community and the public. This
      process begins with voluntary submission of reports of possible vaccine
      associated events to VAERS by the informed and conscientious health professional.

PMID- 15462576
TI  - Tracking Immunization.
AB  - Immunization registries are critical to our ability to maintain high levels of
      immunization, particularly as new vaccines are introduced and immunization
      schedules become more complex. In the future, immunization registries
      increasingly will become components of integrated child health information
      systems. The lessons learned in developing immunization registries will
      facilitate development of these larger, more comprehensive systems.

PMID- 15462577
TI  - Current and preferred housing of psychiatric consumers/survivors.
AB  - As part of a participatory action research project, we surveyed 300 psychiatric
      consumers/survivors from southwestern Ontario regarding their housing preferences
      and housing satisfaction. We found that, while 79% of the sample preferred
      independent living, 76% were living in some other type of setting (e.g.,
      temporary shelter, supportive housing, sheltered care). Those living in temporary
      shelters reported the lowest levels of housing satisfaction, and those who were
      living in the type of housing that they preferred had the highest levels of
      housing satisfaction. This information is being used by stakeholder groups
      involved in the project to help build the capacity of the community to provide
      the types of housing that are preferred by consumers/survivors.

PMID- 15462578
TI  - Growing older: the lived experience of older persons with serious mental illness.
AB  - The purpose of this qualitative paper is to describe, from the consumers'
      perspective, the complex factors involved as persons with serious mental illness
      grow older in the community. The results consisted of seven major themes subsumed
      under three categories. The first category, across the lifespan, included three
      themes: (a) older but wiser, (b) one day at a time, and (c) echoes from the past.
      The second category, factors impeding participation in the life of the community,
      also included three themes: (a) on the outside looking in, (b) walk a mile in my
      shoes, and (c) without a voice. The final category, factors which enhance
      participation in community life, included only one theme: meaningful activities
      and productive roles. Findings suggest that service providers must actively
      involve consumers as primary members of the rehabilitation team to deliver
      effective, individualized services which are designed around the particular
      future needs and resources of older persons with serious mental illness.
      Furthermore, stigma reduction through advocacy and education at the community
      level must be strengthened.

PMID- 15462580
TI  - Investigating issues surrounding depression in adolescent girls across Ontario: a
      participatory action research project.
AB  - This study gathered data from adolescent girls in four regions (Ottawa, North
      Bay, Toronto, Windsor) concerning key issues in the prevention of depression in
      young women. Using a participatory methodology, a team of young women worked with
      researchers to design and conduct focus groups with 48 adolescent girls across
      Ontario. Major themes emerging from the focus group data fell into five
      categories: (a) symptoms, (b) contributing factors, (c) alleviating depression,
      (d) prevention, and (e) barriers to receiving help. These findings should be
      considered when designing programs targeting depression in young women in order
      to maximize the accessibility and effectiveness of such initiatives.

PMID- 15462579
TI  - [Social and professional rehabilitation for people presenting with severe mental
      disorders].
AB  - Supported employment programs for people with severe mental disorders offered by
      2 agencies in the Quebec City area were assessed after 10 years of operation. The
      study, which followed 30 participants over a period of 10 months, found gains in
      the areas of improved self-esteem, greater capacity to deal with daily stress,
      enhancement of quality of life and acquisition of vocational skills. Results are
      discussed in the light of existing knowledge on integration into the workplace.

PMID- 15462581
TI  - Community resilience or unidentified health risk?: health professional
      perceptions on the impact of the Swissair Flight 111 disaster on surrounding
      communities.
AB  - On September 2nd, 1998 Swissair Flight 111 crashed in Saint Margaret's Bay, Nova
      Scotia. Surrounding coastal communities were immediately transformed into
      disaster response sites. Sixteen community health professionals were interviewed
      that identified several types of individual and community exposure, including
      exposure to human remains. The interviews revealed that the coastal communities
      have responded with silence and stoicism. This silence has been viewed by some
      health professionals as resilience. The interface of a major disaster, community
      silence, low help-seeking behaviours, and limited disaster health responses
      raises the critical question whether this is a profile of resilience or a
      community silently enduring.

PMID- 15462582
TI  - [The Better Beginnings, Better Futures Project: short-term effects on the
      children of Cornwall].
AB  - The Ontario Better Beginnings, Better Futures Project is a prevention project for
      young children and their families living in 8 disadvantaged neighbourhoods
      throughout the province. The Cornwall site of Better Beginnings, Better Futures
      ("Partir d'un bon pas pour un avenir meilleur"), the only francophone site of the
      project, has focused on children aged 4 to 8 in 4 francophone schools. This
      article presents the short-term effects of the programs on the children of
      Cornwall after 4 years of operation. Results showed a decrease in teacher ratings
      of behaviour problems and an increase in teacher ratings of prosocial behaviour.
      There was also a significant improvement in nutrition and health care. Finally,
      results showed a decrease in the number of students receiving special education
      services for learning disabilities or behavioural problems. However, results
      failed to show significant improvements in cognitive functioning or academic
      achievement.

PMID- 15462583
TI  - A process and outcome evaluation of a shelter for homeless young women.
AB  - To evaluate the processes and outcomes of a short-term shelter, both quantitative
      and qualitative data were gathered via participant observation, focus group
      interviews with shelter staff and residents, and individual interviews with a
      sample of 40 young women who had been homeless prior to using the shelter. The
      process evaluation showed that the shelter staff strived to utilize an
      empowerment philosophy in their relationships with residents, but that there were
      many challenges to implementing this philosophy. The outcome evaluation showed
      that, at a 3-month follow-up, the participants reported significant improvements
      in housing, income, independence, and life satisfaction, but most continued to
      experience poverty and a number of other difficulties. The results were discussed
      in terms of the implications for future research and the valueand limitations of
      shelters for dealing with homeless youth. The need for more sustained and
      comprehensive program interventions and supportive social policies was
      underscored.

PMID- 15462584
TI  - Substance use among persons with serious mental illness in eastern Ontario.
AB  - One hundred and eighty persons with serious mental illness (SMI) in eastern
      Ontario, receiving services from assertive community treatment teams in
      Brockville and Kingston were interviewed about substance use. Data were compared
      to survey findings for the Ontario population. Tobacco use was higher among both
      men and women in the SMI sample, but use of alcohol and drugs in the past 12
      months was lower than population data. The frequency of alcohol use was
      significantly greater than drug use among the SMI sample.

PMID- 15462585
TI  - Investigation of photon beam models in heterogeneous media of modern
      radiotherapy.
AB  - This study investigates the performance of photon beam models in dose
      calculations involving heterogeneous media in modern radiotherapy. Three dose
      calculation algorithms implemented in the CMS FOCUS treatment planning system
      have been assessed and validated using ionization chambers, thermoluminescent
      dosimeters (TLDs) and film. The algorithms include the multigrid superposition
      (MGS) algorithm, fast Fourier Transform Convolution (FFTC) algorithm and Clarkson
      algorithm. Heterogeneous phantoms used in the study consist of air cavities, lung
      analogue and an anthropomorphic phantom. Depth dose distributions along the
      central beam axis for 6 MV and 10 MV photon beams with field sizes of 5 cm x 5 cm
      and 10 cm x 10 cm were measured in the air cavity phantoms and lung analogue
      phantom. Point dose measurements were performed in the anthropomorphic phantom.
      Calculated results with three dose calculation algorithms were compared with
      measured results. In the air cavity phantoms, the maximum dose differences
      between the algorithms and the measurements were found at the distal surface of
      the air cavity with a 10 MV photon beam and a 5 cm x 5 cm field size. The
      differences were 3.8%. 24.9% and 27.7% for the MGS. FFTC and Clarkson algorithms.
      respectively. Experimental measurements of secondary electron build-up range
      beyond the air cavity showed an increase with decreasing field size, increasing
      energy and increasing air cavity thickness. The maximum dose differences in the
      lung analogue with 5 cm x 5 cm field size were found to be 0.3%. 4.9% and 6.9%
      for the MGS. FFTC and Clarkson algorithms with a 6 MV photon beam and 0.4%. 6.3%
      and 9.1% with a 10 MV photon beam, respectively. In the anthropomorphic phantom,
      the dose differences between calculations using the MGS algorithm and
      measurements with TLD rods were less than +/-4.5% for 6 MV and 10 MV photon beams
      with 10 cm x 10 cm field size and 6 MV photon beam with 5 cm x 5 cm field size,
      and within +/-7.5% for 10 MV with 5 cm x 5 cm field size, respectively. The FFTC
      and Clarkson algorithms overestimate doses at all dose points in the lung of the
      anthropomorphic phantom. In conclusion, the MGS is the most accurate dose
      calculation algorithm of investigated photon beam models. It is strongly
      recommended for implementation in modern radiotherapy with multiple small fields
      when heterogeneous media are in the treatment fields.

PMID- 15462586
TI  - Peristaltic transport of a Casson fluid in an asymmetric channel.
AB  - The peristaltic transport of a Casson fluid in a two-dimensional asymmetric
      channel is studied under long- wavelength and low-Reynolds number assumption. The
      asymmetry in the channel is created by considering the peristaltic waves imposed
      on the boundary walls to possess different amplitude and phase. The analysis of
      the flow is carried out in a wave frame of reference moving with the velocity of
      the wave. Due to the asymmetry in the channel two yield planes exist and they are
      calculated by solving the transcendental equation in terms of the core width. In
      an asymmetric channel the yield planes are skewed towards the boundary with
      higher amplitude or a phase difference in relation to the other boundary. While
      in a symmetric channel the yield planes are located symmetrically on either side
      of the axis of the channel. The phenomena of trapping and reflux have been
      discussed in the symmetric case of the channel. It is noticed that trapping of
      fluid occurs and the trapping zone extends for an increase in the time average
      flux. It is found that reflux occurs for higher values of amplitude of the
      peristaltic wave and the reflux zone extends for increased amplitudes.

PMID- 15462587
TI  - Prostate dosimetry in an anthropomorphic phantom.
AB  - Four field prostate treatments are a standard treatment procedure in
      radiotherapy. Dose in the prostate and rectum region were calculated for 6MV and
      18MV photon beams on an anthropomorphic phantom with a collapsed cone convolution
      method using a 3-D planning system. Validation has been performed with
      radiographic film and thermoluminescent dosimeters. Results have shown that the
      pinnacle planning system has accurately modelled doses delivered to a
      heterogeneous phantom with calculations and measurements agreeing within +/-3%
      over most areas. When treating clinically, considerations such as the volume of
      bowel gas should be taken into account when planning. A sample of patient CT
      scans showed that in the absence of a heterogeneity correction, the error in
      estimated dose through the rectum could be as high as 8% in the presence of large
      volumes of rectal gas. Considerations, such as whether the patient undergoes
      another CT scan, the bowel gas volume ignored or assigned a specific density
      needs to be taken into account and brought to the attention of the radiation
      oncologists for accurate treatment.

PMID- 15462588
TI  - A CMOS image sensor method of focal spot size measurement.
AB  - A phosphor opto-coupled monochrome CMOS image sensor with a slit diaphragm was
      used to investigate focal spot characteristics. Images were captured during x-ray
      exposure with a triggered frame grabber and subsequently enhanced. Dimensions of
      the focal spot width (1.39mm) and length (1.92mm) were determined from the focal
      spot intensity profiles and their corresponding Full Width at Half Maxima (FWHM)
      in two orthogonal orientations. The CMOS image sensor measurements demonstrated
      differences in the measured width and length dimensions when compared to film
      measurements. The obtained nominal focal spot values however showed that image
      sensor determined focal spot dimensions agreed with the direct film and film
      screen methods when based on the AS/NZS defined nominal focal spot values. The
      CMOS image sensor tested appears to lack the measurement accuracy required for
      the measurement of small focal spot sizes due in part to its limited camera
      sensitivity.

PMID- 15462589
TI  - Compensation of limb weight on interfaced raw torque signals from a KIN-COM
      dynamometer to an AMLAB workstation.
AB  - The effect of gravity should be considered when using isokinetic devices to
      measure human movement performance. In most isokinetic dynamometers gravity
      compensation is controlled by software through a gravity correction option.
      However in some complex research protocols the dynamometer signal acquisition and
      processing capability is not adequate to effectively synchronize or process a
      wide range of captured signals. Therefore when the force/torque signals from a
      commonly used dynamometer such as KIN-COM are interfaced into a signal processing
      workstation such as AMLAB, it is necessary to further process the received raw
      signals for gravity correction. The aim of this study was to evaluate the
      effectiveness of an AMLAB-based instrument designed for gravity compensation of
      raw torque signals acquired from a KIN-COM dynamometer. To check the accuracy of
      weight compensation within the AMLAB, environment, torque signals produced by a
      known weight during a 180-degree range of KIN-COM lever arm movement were
      compared with and without weight compensation. The results indicated that this
      technique is an accurate means for weight compensation when raw torque signals
      from a KIN-COM dynamometer are interfaced to an AMLAB workstation.

PMID- 15462590
TI  - [Legal implications of human genome].

PMID- 15462591
TI  - [Effects of hyperthyroidism on bone mass in women of reproductive age].
AB  - INTRODUCTION: Hyperthyroidism is one of the most frequent endocrinopathies in
      women of reproductive age. Consequently, increased risk of osteoporosis may be
      expected. MATERIAL AND METHODS: The research has included a group of 30
      hyperthyroid women and a control group of 30 healthy women of reproductive age.
      Age and some clinical characteristics were analyzed, as well as some
      anthropometric parameters. Bone mass parameters were determined by measuring bone
      mineral density using ultrasound devices (SAHARA-Hologic). RESULTS: Bone mass
      parameters in hyperthyroid women are significantly lower than in controls (BUA:
      63.25+/-12.17; 69.73+/-10.02 dB/MHz respectively; SOS: 1523.90+/-24.47; 1540.19+/
      26.59 m/s respec. QUI/STIFF 79.78+/-13.95; 89.09+/-13.99% respec.) Duration of
      hyperthyroidism affects bone density and reduces it. DISCUSSION: Obtained results
      were expected, having in mind that hyperthyroidism is a condition characterized
      by increased bone catabolic rate. Also, negative correlation between the duration
      of hyperthyroidism and bone mass parameters (BUA, SOS) was expected, because it
      is logical that consolidation of bone mass in adult life cannot be maintained in
      circumstances in which metabolic rate is increased. During hyperthyroidism, bone
      loss is expected. In order to confirm this, future studies of bone markers are
      necessary. CONCLUSION: Based on results obtained in the study, the following
      conclusions were made: hyperthyroidism is accompanied by decreased values of bone
      mass parameters; this effect depends on duration of hyperthyroidism. We confirmed
      that hyperthyroidism may be the cause of decrease in bone mass, particularly if
      it lasts more than a year. To prevent osteoporosis in women of reproductive age
      with hyperthyroidism and involutional osteoporosis later in life, early diagnosis
      and effective therapy of hyperthyroidism is imperative.

PMID- 15462592
TI  - [Sexual behaviour of adolescents].
AB  - INTRODUCTION: Numerous studies have shown that sexual behaviour increases among
      adolescents. Disharmony between biological and psychosocial maturity among young
      people may cause risky behavior, and endanger psychophysical and reproductive
      health of young persons. MATERIAL AND METHODS: A questionnaire on sexual
      behaviour was completed by 169 adolescents, 1st and 4th year high school
      students. RESULTS: Every 6th first grade and every 2nd fourth grade adolescent is
      sexually active. Male adolescents begin sexual activities significantly earlier
      (at the age of 15.6) than female adolescents (16.5). Also, young men have
      significantly more partners (3.6) than girls (1.3), and more parallel sexual
      relations than girls. Only 1/3 of sexually active adolescents always use some
      kind of contraception, more frequently boys (41.9%) than girls (26.7%).
      DISCUSSION: Early commencement of sexual activity results with longer active
      period before realization of the reproductive function, which increases risk for
      reproductive health disorders. Unprotected sexual intercourse and large number of
      partners also present significant risk factors. CONCLUSION: Sexual life of
      adolescents begins at the age of 16, on average, and only every third always uses
      contraceptive protection, which points to a need for better education on
      reproductive health by using contemporary methods. It is also necessary to
      increase availability of contraceptives (condoms) at all places where adolescents
      spend time (in schools, bars, cinemas, disco clubs etc.) in order to achieve
      responsible sexual behavior and protection of reproductive health among youth.

PMID- 15462593
TI  - The role of cellular development and cell death in neurochemical organization and
      integrative brain functions--normal and pathological.
AB  - In terms of systemic aspects of common molecular mechanisms of development,
      important part of which is the process of cellular death and integrative activity
      of nervous system, a complex clinical-experimental study of effects of various
      neurotrophic and apoptotic factors (proteins S100b, HLDF, brain lectins CSL and
      R1) on learning and memory and ischemic stroke was performed. Data concerning
      specific and heterochronic participation of these factors in neurochemical
      mechanisms of learning and memory in mechanisms of ischemic stroke formation were
      established. Changes of examined factors and their antibodies as well as the
      dynamics of changes in sera and cerebrospinal fluid can be considered as
      prognostic markers of ischemic stroke and efficiency of therapy.

PMID- 15462594
TI  - The role of laparoscopy in gynecologic oncology.
AB  - In some patients and when performed by a skillful surgeon, gynecologic oncologist
      familiar with advanced laparoscopic techniques, laparoscopy results with less
      surgical trauma, reduced blood loss and hospitalization, and faster recovery. The
      complication rate has been found to increase as the complexity of the operation
      rises, but it is not higher than in open surgery. Preliminary studies show that
      recurrence and survival rates are comparable to those reported for patients
      treated by a standard abdominal approach. Future randomised trials are necessary
      to deal with long term recurrences and survival data and benefits of laparoscopy
      in management of gynecologic malignancies. At our institution 97 cancer patients
      underwent laparoscopic procedures, without complications: explorative and staging
      laparoscopies with biopsies of ovaries, peritoneal biopsies, retroperitoneal and
      mesenteric tumours; second look laparoscopy, ovariectomy, laparoscopic assisted
      vaginal hysterectomy (LAVH). Advanced ovarian cancer was found in 3 patients and
      laparotomy was performed. No complications were established.

PMID- 15462595
TI  - [Early diagnosis of cytomegalovirus infections in organ recipients].
AB  - INTRODUCTION: Cytomegalovirus (CMV) infections and acute rejection of organs are
      the commonest complications in the early posttransplantation period. Clinical
      picture of CMV reactivation in organ recipients may have a dramatic course,
      occasionally even with a fatal outcome. DIAGNOSIS OF CMV: In order to prevent
      acute rejection of organs in the posttransplantation period, patients are
      subjected to immunosuppressive therapy, which sustains reactivation of CMV. Thus,
      early diagnosis of CMV infections before clinical assay of CMV, is of crucial
      importance. Early diagnosis allows preventive antiviral therapy. Conventional and
      contemporary diagnostic tests are presented, with particular review on their
      interpretation and significance in prevention of CMV infections. Present
      serologic tests are positive a few weeks after infection, which is late for organ
      recipients. Cytopathogenic effects characteristic for CMV occur several weeks
      later. Antigenemia assay is a fast, quantitative test for detection of early CMV
      antigen pp65. Methods of molecular biology represent the latest innovation in the
      laboratory diagnosis of posttransplantation CMV infections. However, they have
      been in use only lately, and therefore their use and significance are still not
      sufficiently experienced. Standardization is thus required, in order to provide
      comparison between various diagnostic centres.

PMID- 15462596
TI  - [Histological characteristics of oral leukoplakia].
AB  - INTRODUCTION: Leukoplakia (LKP) is defined as a white patch or plaque on the
      mucosa of oral cavity, vulva, vagina etc., which cannot be removed and cannot be
      clinically or microscopically explained by presence of a disease. LKP is included
      in the group of lesions with malignant potential. MICROSCOPIC CHARACTERISTICS:
      Basic microscopic characteristics of oral LKP include hyperkeratosis of ortho- or
      parakeratotic type and acanthosis of the epithelium, with various degrees of
      chronic inflammatory infiltrates in lamina propria. Also, various degrees of
      epithelial dysplasia may occur. Some of the most important microscopic
      characteristics of dysplasia are: loss of polarity of basal cells, increased
      nuclear cytoplasmic ratio, irregular epithelial stratification, increased number
      of abnormal mitotic figures and their presence in the superficial epithelium,
      cellular and nuclear pleomorphism, keratinization of single cell groups.
      MALIGNANT POTENTIAL: LKP is the most common oral mucosal lesion (evident in 3% of
      adults). At the same time, up to 85% of all precancerous lesions are manifested
      as LKP. Overall malignant potential of LKP does not exceed 4%, but some authors
      found that even 16% LKP with some degree of dysplasia, have a potential to
      transform to carcinoma. MICROSCOPIC DIFFERENTIAL DIAGNOSIS: The most important
      differential diagnostic criteria are listed for lesions with similar microscopic
      appearance. CONCLUSION: Nowdays LKP is diagnosed more frequently than before,
      probable due to a better patients' education and dentists' caution, but not due
      to real increase in incidence.

PMID- 15462597
TI  - [Pregnancy as a psychological event].
AB  - INTRODUCTION: Apart from physiological and somatic changes, pregnancy is a
      complex phenomenon which also includes psychological and social changes.
      Pregnancy, especially the first one, represents a powerful psychological event.
      This paper deals with pregnancy as a psychological event, considering
      psychological changes in the course ofpregnancy as a stressful event.
      PSYCHOLOGICAL CHANGES DURING PREGNANCY: Pregnancy is always associated with
      changes in psychological functioning of pregnant women. It is usually associated
      with ambivalence, frequent mood changes, varying from anxiety, fatigue,
      exhaustion, sleepiness, depressive reactions to excitement. During pregnancy,
      changes include body appearance, affectivity and sexuality, whereas the position
      and role of women attains a new quality. Even thoughts of pregnancy can bring
      about numerous worries about its course and outcome, and especially of the
      delivery itself, which may be so intense that they acquire a features of phobia
      (which may be the reason for avoiding pregnancy). PREGNANCY AS A STRESSFUL EVENT:
      Pregnancy is identified as a potent stressor that can seriously affect the
      psychic status of pregnant women, perinatal outcome, but also psychic functioning
      of the new-born individual. Appropriate relationship of partners and support of
      the society play an important role in overcoming stress during pregnancy.
      CONCLUSION: Pregnancy is an event that involves numerous somatic and
      psychological changes. However, pregnancy can also be a potent stressor.
      Existence of prenatal maternal stress may lead to different perinatal
      complications that may have long-term consequences on the newborn. In prevention
      of maternal stress emphasis has to be put on partner's emotional support, as well
      as empathy of the social environment. However, in certain cases, professional
      psychotherapeutic support is necessary, in form of short supportive treatment.
      Preventive measures should include adequate psychological support during
      pregnancy, especially the first one, provided for all pregnant women, but also
      for those women that plan to get pregnant in the near future.

PMID- 15462599
TI  - [Occupational stress and arterial hypertension].
AB  - INTRODUCTION: Arterial hypertension is an important medical, social and economic
      problem in the working population. Factors of occupational exposure lead to a
      much faster and more frequent occurrence of this disease and its consequential
      complications. Among these factors the following take an important place: noise,
      carbon monoxide, job dissatisfaction, microclimate conditions, chemical agents,
      shift work night work monotonous work and so on. The purpose of this study was to
      analyze working conditions, working environment, work demands and identification
      of occupational stressors and their influence on development of arterial
      hypertension. MATERIAL AND METHODS: This investigation included 3470 workers and
      it examined technological processes, working time, job sastisfaction,
      interpersonal relations and physical and chemical hazards of their workplaces.
      The exposed group consisted of 2270 workers occupationally exposed to stressors.
      Control group included 1200 workers whose workplaces were without stressors.
      Workers of exposed group were divided into 14 subgroups in regard to presence of
      occupational hazards. RESULTS: Arterial hypertension was established in 39.9% of
      workers of exposed group, which is statistically significantly more than in
      controls (25.7%). The highest prevalence of arterial hypertension was at workers
      who were dissatisfied with the job and who were at the same time occupationally
      exposed to noise and carbon monoxide. Family predisposition and smoking have
      cumulative effects with occupational hazards. DISCUSSION: Possible mechanisms of
      arterial hypertension development include activation of adrenergic nervous
      system, renin-angiotensin aldosterone system, higher concentrations of steroids,
      catecholamines and free radicals caused by occupational hazards. CONCLUSION:
      Occupational stressors are significant factors in development of arterial
      hypertension of exposed workers. The most important stressors are noise, carbon
      monoxide and job dissatisfaction.

PMID- 15462598
TI  - [Predictors of mortality in dialysis patients--association between malnutrition,
      inflammation and atherosclerosis (MIA syndrome)].
AB  - INTRODUCTION: Numerous recent studies have shown increased comorbidity and
      mortality in dialysis patients with malnutrition. Protein-energy malnutrition
      with muscle wasting occurs in a large proportion of patients with chronic renal
      failure and is, in addition to atherosclerosis, a strong risk factor for
      mortality in patients undergoing dialysis. Malnutrition is also associated with
      increased cardiovascular mortality in dialysis patients. PATHOGENIC FACTORS OF
      MALNUTRITION IN DIALYSIS PATIENTS: Malnutrition is associated with a number of
      metabolic and vascular abnormalities. These factors include hypoalbuminemia,
      dyslipidemia with raised triglyceride concentrations, low-density lipoprotein and
      very low-density lipoprotein concentrations, insulin resistance and high
      concentrations of acute-phase proteins. Low serum albumin concentration, usually
      used as an index of malnutrition, is highly associated with increased mortality
      risk in dialysis patients. However, serum albumin is affected by factors other
      than malnutrition and high concentrations of acute-phase proteins, such as C
      reactive protein (CRP), which correlate with low serum albumin in malnourished
      patients on dialysis. Oxidative stress has emerged as an important cofactor for
      development of endothelial dysfunction as premature atherosclerosis. In this
      context, malnutrition, inflammation and markers of oxidative stress are
      associated with vascular diseases. ETIOLOGY OF MALNUTRITION IN DIALYSIS PATIENTS:
      In recent studies several reports have suggested that inflammation, alone or in
      combination with low protein intake, plays a significant role in etiology of
      malnutrition in uremic patients. Lipid abnormalities may not only be a
      consequence of renal disease, but also contribute to its progression. Lipoprotein
      (a) is also associated with various atherosclerotic diseases. THERAPY OPTIONS:
      New treatment strategies, such as high protein/energy vs. standard protein/energy
      nutritional regimens, are necessary as well as food intake and dietary
      supplements. Intensive supplementation of (1.5 g protein/kg/d and 45 kcal/kg/d)
      is necessary to improve nutritional status of dialysis patients. CONCLUSION:
      Cellular basis of pathogenetic factors in malnutrition is unclear. It is,
      however, now recognized that oxidative stress and inflammatory cytokine
      aggravates the nutritional status of these patients.

PMID- 15462600
TI  - [Possibilities of endoscopic treatment of primary vesicoureteral reflux].
AB  - INTRODUCTION: Vesicoureteral reflux, urinary infection and pyelonephritic
      scarring represent a well known triad in pediatric practice that may lead to
      severe scarring of kidneys, and development of so called reflux nephropathy.
      Apart from standard therapeutic options (conservative treatment and surgical
      therapy), endoscopic correction of refluxing vesicoureteral junction has been
      introduced into clinical practice. MATERIAL AND METHODS: This study included
      endoscopically treated patients with primary vesicoureteral reflux over a 9-year
      period, as well as certain clinical parameters. RESULTS: Endoscopic correction of
      primary vesicoureteral reflux with teflon paste has been successful in up to
      93.5% of patients. After one application vesicoureteral reflux disappeared in
      58.8% of cases. After two applications 86.0% of ureters were cured, whereas the
      third application had no further effect on existing reflux. Improvement with
      spontaneous regression of reflux was established in 7.5% of treated ureters.
      DISCUSSION: Endoscopic correction should be performed in all patients with third
      grade vesicoureteral reflux, and in selected patients with second and fourth
      grade reflux. First grade reflux should be treated conservatively, and fifth
      grade reflux should be treated surgically. CONCLUSION: Endoscopic treatment of
      primary vesicoureteral reflux is an easy, simple, fast and safe procedure that
      prevents regurgitation of urine from bladder to upper parts of the urinary system
      in most of cases.

PMID- 15462601
TI  - [Sense of smell in patients with bilateral nasal polyposis].
AB  - INTRODUCTION: Sense of smell is susceptible to various changes, both in
      physiological and in numerous pathological conditions. Of quantitative disorders
      of smell, hyposmia and anosmia are quite common, whereas of qualitative disorders
      parosmia is most frequent. The aim of this paper was to examine impact of
      bilateral nasal polyposis on olfactory function. MATERIAL AND METHODS: The
      research was carried out at the Nose, Ear and Throat Clinic in Novi Sad. It
      included 80 examinees, 40 (20 male, 20 female) with bilateral nasal polyposis,
      while 40 examinees belonged to the control group (20 male, 20 female) without
      symptoms of nasal polyposes. Fortunato-Niccolini olfactometer was used for this
      examination. RESULTS AND DISCUSSION: In patients with bilateral nasal polyposis
      the average perception threshold values for examined odors were 15.50 ccm of
      odorous air, while in the control group they were 10.20 ccm of odorous air. The
      average identification threshold values for examined odors in patients with
      bilateral nasal polyposis were 18.80 ccm of odorous air, while in the control
      group they were 13.55 ccm of scented air. T-test showed that values of both
      thresholds were statistically significantly higher (p<0.01) in patients with
      bilateral nasal polyposis in relation to the control group. CONCLUSION: Olfactory
      deficit in patients with bilateral nasal polyposis is explained by difficult or
      impossible passage of odors into the olfactory region.

PMID- 15462602
TI  - [Treatment of metastatic neck squamous cell carcinomas with unknown primary].
AB  - INTRODUCTION: Treatment of metastatic neck squamous cell carcinomas of unknown
      primary is one of the most serious problems in head and neck oncology. MATERIAL
      AND METHODS: Fifty-one patients were analyzed during the period 1977-1997. All
      patients underwent clinical examination of head and neck, hematological and
      laboratory tests, X-ray of paranasal sinuses, esophagus and lungs, scintigraphy
      of the thyroid gland, epipharyngoscopy, esophagoscopy and
      laryngotracheobronchoscopy, biopsy of suspected changes and blind biopsy of
      suspected regions (epipharynx, tongue base, piriform sinus), ipsilateral
      tonsillectomy (17 patients), examination of gastrointestinal tract, kidneys,
      prostate, testicles, and breasts and ovaries, respectively. RESULTS: Almost half
      of metastases developed in the II level of the neck (49.01%; 25/51). Most
      metastases were 3-6 cm in diameter (N2)--60.76% (31/51). Forty patients were
      surgically treated by various neck dissection methods and postoperative
      radiotherapy (60 Gy). Palliative radiotherapy was applied in patients with
      inoperable metastases. Eighteen patients had a five-year disease free survival
      (35.29%). DISCUSSION: Metastases localized in the II and III levels of the neck
      and in the upper two-thirds of the V level, should be primarily treated by neck
      dissection. Lymph nodes up to 3 cm in diameter (N1) are operated by a modified
      radical neck dissection. Lymph nodes over 3 cm (N2) and 6 cm in diameter (N3) are
      operated by radical or extended radical neck dissection. CONCLUSION: Primary
      surgery plus postoperative radiotherapy provide satisfactory results in therapy
      of metastatic squamous cell carcinomas of the neck with unknown primary.

PMID- 15462603
TI  - [Heredity of psoriasis].
AB  - INTRODUCTION: Epidemiological studies of twins show that there is a genetic
      predisposition to psoriasis. Researches conducted so far show that psoriasis is a
      multifactorial polygenetic disease with reduced gene penetration. They also show
      that heredity is more significant than the "trigger" factor whose influence is
      limited to the exchange of phenotypes. Researches in USA, Canada and Europe
      identified four most important loci (psoriasis susceptibility--1-4). At least one
      is in MHC (major histocompatibility complex) due to the connection between
      psoriasis and alleles of human leukocyte antigen (HLA). OBJECTIVE: Our study
      included 117 patients and examined the indicators of genetic predisposition to
      psoriasis: frequency of psoriasis among relatives of psoriatic probands;
      frequency of psoriasis among relatives (I and II degree) of psoriatic patients;
      age of probands and other relatives at the onset of illness. MATERIAL AND
      METHODS: We have used a structured questionnaire for collection of data about
      existence of psoriasis in relatives of I and II degree of psoriatic probands and
      about the age of probands and relatives at the time of onset. RESULTS AND
      DISCUSSION: Twenty six (21.85%) probands have at least one ill relative. The
      examined patients who have diseased relatives get ill much earlier than those who
      do not. Probands with two or more diseased relatives get ill much earlier than
      those who have just one diseased relative. Analysis of our sample shows a
      significant statistical difference regarding the onset of illness of diseased
      parents and their children. Children get ill earlier. CONCLUSIONS: We have
      concluded that in our sample there is a hereditary component which is related to
      frequency and onset of psoriasis.

PMID- 15462604
TI  - [Effects of systematic lymphadenectomy on length of survival in patients with
      gastric carcinoma].
AB  - INTRODUCTION: In the last few years there have been arguments between the
      Japanese and West European surgeons about benefits of systematic
      lymphadenectomies in surgery of gastric cancer. In this paper we would like to
      point out effects of systematic lymphadenectomies on survival of patients with
      gastric carcinoma. MATERIAL AND METHODS: This investigation included two groups
      of patients. The first group of 126 patients with gastric carcinoma underwent
      peritumor lymphadenectomy D1. The second group of 114 patients with gastric
      carcinoma underwent more radical types of lympadenectomy (D2, D2+, D3). Survival
      analysis included investigation of the following: 1. depth of tumor invasion, 2.
      metastatic involvement of the lymph nodes 3. tumor stage, 4. tumor recurrence.
      RESULTS: Most of examined patients presented with invasion and serosal and
      subserosal penetration (about 75% in both groups). More than 42% of lymph nodes
      had metastases and patients with systematic lymphadenctomy had better survival.
      Patients without subserosal invasion did not have metastatic lymph nodes in II,
      III, IV drianaged groups. There was no difference in regard to length of survival
      between the two analyzed group. 5-year survival rate was highest in stage I of
      gastric carcinoma (86%), but in stage IV 5-year survival rate was only 3.8%.
      Local recurrence (26%) and lymph node metastases (53%) were common causes of
      tumor recurrence in group with peritumor lymphadenectomy. In all groups of
      patients with advanced gastric cancer patients undergoing systematic
      lymphadenectomy presented with higher survival rate. DISCUSSION: Patients with
      advanced gastric cancer presented with higher number of metastatic lymph nodes in
      III and IV drainaged groups. In this stage systematic lympadenectomy played the
      main role. In the group of early gastric cancer there were no patients with
      metastatic lymph nodes in drainaged groups. CONCLUSION: D2 lympahedenectomy is a
      standard procedure for a great number of patients with gastric carcinoma, with
      high survival rate. Only in the group of advanced gastric cancer, patients
      undergoing more radical types of lymphadenectomies (D2+, D3) presented with
      better survival rates.

PMID- 15462605
TI  - [Osteomas of the middle ear].
AB  - INTRODUCTION: Osteomas of the middle ear are small, single, usually unilateral,
      peduncular growths, off-white in colour, with smooth or multilobular surface,
      asymptomatic or causing functional disorders (progressive hearing loss,
      pathological appearance of the eardrum, vertigo and otorrhea), of unclear or
      unknown etiology. Fleury described three types of osteomas: massive, diffuse
      atticoantral and localized type. The therapy is surgical. Small and asymptomatic
      ones are followed-up. Cremers suggests surgical intervention in cases of
      progressive growth and increased hearing loss. CASE DESCRIPTION: Discharge and
      pain in the left ear started twelve years ago, accompanied by impaired hearing
      and tinnitus. Four months ago the symptoms aggravated and discharge and pain
      increased Otomicroscopic findings revealed: perforation in the posterior attic
      and a prominent polypous, clustered bright red formation. Schuller X-ray showed
      total absence of pneumocyte cells, with distinct sclerotic changes.
      Retroauricular access showed a biventricular bony formation in the cavum and
      partly in the antrum. A cholesteatoma extended from the cavum into the antrum,
      above the osteatoma. The bony formation was separated transmeatally from the grip
      in the posterior attic using a chisel, partially removing the bone wall of the
      exterior aural tube, removing it completely through the mastoid antrum. The
      removed bony mass, sized 5 x 8 x 8 mm, included also the incus. DISCUSSION:
      Osteoma was discovered accidentally. Regarding clinical features, it belonged to
      the second group, due to progressive hearing loss, recurrent episodes of
      otorrhea, pain, biventricular shape and association with cholesteatoma. It was
      removed using a combined method. It was not possible to establish when the
      osteoma exactly started generating. It is possible that the initial complaints
      twelve years ago were the first signs of illness, and chronic otitis may have
      occurred as a consequence of the tumor.

PMID- 15462606
TI  - Costs and benefits of genomics patents.
AB  - Genomics patents are controversial on religious, ethical, legal, and economic
      grounds. An economic approach is desirable for valuing the patent system
      generally, and genomics patents in particular, in terms of its stated
      constitutional objective, which is to 'promote progress'. Several types of
      criticisms and warnings have been issued regarding the suitability of genomics
      inventions for patent protection; here these are evaluated in the context of more
      general concerns about the efficacy of the patent system. As with the patent
      system more generally, it is difficult to specify an alternative mechanism for
      producing inventions that has attributes (such as decentralized resource
      allocation, speed of therapeutic discovery, and financing by beneficiaries) that
      are predictable enough to serve as a benchmark against which to judge the current
      regime, which is dominated by genomics patents. The current patent regime can be
      expected to produce commercializable therapies reasonably reliably, while many
      proposed alternatives hearken back to a regime that did not produce
      commercializable therapies with as great speed or variety. Therefore, the onus
      appears to lie on the critics to create a model with the desirable properties of
      the patent system, but with fewer of its acknowledged weaknesses, such as
      'monopoly' pricing and 'patent thickets'.

PMID- 15462607
TI  - Human genetics and responses to influenza vaccination: clinical implications.
AB  - Influenza A and B viruses are negative-strand RNA viruses that cause regular
      outbreaks of respiratory disease and substantially impact on morbidity and
      mortality. Our primary defense against the influenza virus infection is provided
      by neutralizing antibodies that inhibit the function of the virus surface coat
      proteins hemagglutinin and neuraminidase. Production of these antibodies by B
      lymphocytes requires help from CD4+ T cells. The most commonly used vaccines
      against the influenza virus comprise purified preparations of hemagglutinin and
      neuraminidase, and are designed to induce a protective neutralizing antibody
      response. Because of regular antigenic change in these proteins (drift and shift
      mutation), the vaccines have to be administered on an annual basis. Current
      defense strategies center on prophylactic vaccination of those individuals who
      are considered to be most at risk from the serious complications of infection
      (principally individuals aged >65 years and those with chronic respiratory,
      cardiac, or metabolic disease). The clinical effectiveness of influenza virus
      vaccination is dependent on several vaccine-related factors, including the
      quantity of hemagglutinin within the vaccine, the number of doses administered,
      and the route of immunization. In addition, the immunocompetence of the
      recipient, their previous exposure to influenza virus and influenza virus
      vaccines, and the closeness of the match between the vaccine and circulating
      influenza virus strains, all influence the serologic response to
      vaccination.However, even when these vaccines are administered to young fit
      adults a proportion of individuals do not mount a significant serologic response
      to the vaccine. It is not clear whether these nonresponding individuals are
      genetically pre-programmed to be nonresponders or whether failure to respond to
      the vaccine is a random event. There is good evidence that nonresponsiveness to
      hepatitis B vaccine, another purified protein vaccine, is at least partially
      modulated by an individual's human leucocyte antigen (HLA) alleles. Because CD4+
      T cells, which control the neutralizing antibody response to influenza virus,
      recognize antigens in association with HLA class II molecules, we recently
      conducted a small study to investigate whether there was any association between
      HLA class II molecules and nonresponsiveness to influenza virus vaccination. This
      work revealed that the HLA-DRB1*0701 allele was over represented among persons
      who fail to mount a neutralizing antibody response. This preliminary finding is
      important because it potentially identifies a group who may not be protected by
      current vaccination strategies. Further investigation into the role of HLA
      polymorphisms and nonresponse to influenza virus vaccination, and vaccination
      against viruses in general, is clearly required.

PMID- 15462608
TI  - Microarray expression profiling reveals candidate genes for human uterine
      receptivity.
AB  - The endometrium undergoes cyclic changes in response to circulating ovarian
      steroid hormones as it prepares for implantation. This dynamic tissue is well
      suited to microarray expression profiling for elucidation of molecular players
      participating in the maturation of the endometrium and during the process of
      implantation. Recent advances in sequencing the human and mouse genomes and the
      availability of microarray technology and bioinformatic analyses have made
      elucidating these molecular participants and dialogs a reality. Analysis of the
      window of implantation, a temporal and spatially unique period in which the
      endometrium is receptive to embryonic implantation, has revealed numerous
      processes to be occurring simultaneously or sequentially. These include cell
      cycle regulation, angiogenesis, immune modulation of implantation, defense
      mechanisms put into place by antibacterial agents and detoxicants, secretion of
      unique products, transport of ions and water, growth factor actions, steroid
      hormone action and metabolism, and production of extracellular matrix proteins,
      unique cell surface glycoproteins, and a variety of transcription factors, to
      name a few. Several groups have recently conducted studies with human
      endometrium, and remarkable similarities exist with mouse. Also, many genes and
      gene families involved in the unique differentiation process of stromal cell
      decidualization are conserved. In addition, infertility associated with
      endometriosis is partly implantation-based, and gene profiling of such tissue
      during the window of implantation has revealed additional insight into mechanisms
      underlying infertility in this disorder. Global profiling of genes in the
      endometrium, decidua, and at the interface between the trophoblast and the
      decidua, has provided remarkable in sight into endometrial maturation and
      implantation.

PMID- 15462609
TI  - Chemical genomics: probing protein function using small molecules.
AB  - Chemical genomics is concerned with the effects of both genetic variation and
      chemical perturbation on the cellular effects of small molecules. Chemical
      genomics relies on selecting biological networks for study, such as those
      represented by different cell types or disease models, in order to build the
      desired specificity into the experimental design. The most relevant network
      property for such experiments is the global connectivity of all cellular proteins
      comprising the functional ensemble, as illustrated by case studies of the
      evolution of cyclooxygenase inhibitors and heat-shock protein modulators. Recent
      examples of chemical genomic profiling, particularly of different cell types,
      highlight the power of carefully planned experimental approaches in chemical
      genomics. These new approaches demonstrate the use of the genome to find new
      targets or new modes of biological interaction.

PMID- 15462610
TI  - Analysis of microglial gene expression: identifying targets for CNS
      neurodegenerative and autoimmune disease.
AB  - Microglia are the tissue macrophage of the central nervous system (CNS) and their
      activation is among the earliest signs of CNS dysfunction and disease. Because
      microglia express many macrophage markers, they are presumed to act primarily as
      effectors of CNS inflammation and destruction. While such responses are
      beneficial to the extent that they destroy CNS pathogens, these responses do have
      the potential to have neurotoxic outcomes. Consequently, therapies for many CNS
      neurodegenerative and inflammatory diseases have been directed at suppressing
      microglial function. There is evidence to suggest that microglia play an
      important role during CNS development and maintenance of CNS function that may go
      beyond simple defense against pathogens. Molecular analysis of microglial
      phenotypes and function has revealed three striking findings: (i) that microglia
      are a unique CNS-specific type of tissue macrophage; (ii) that they are highly
      heterogeneous within the healthy CNS; and (iii) that microglial responses are
      exquisitely tailored to specific regions of the CNS and specific pathological
      insults. We suggest that ubiquitous suppression (rather than targeted
      manipulation) of microglial function may fail to fully ameliorate CNS pathology
      and may even ultimately promote maladaptive outcomes.

PMID- 15462611
TI  - Polymorphisms in genes involved in the corticosteroid response and the outcome of
      childhood acute lymphoblastic leukemia.
AB  - BACKGROUND: Considerable variability in sensitivity to corticosteroids (CS) has
      been observed among individuals with regard to both the natural and synthetic
      compounds. The role of genetic polymorphisms in modulating CS function, and hence
      in disease susceptibility, has been extensively analyzed. Their impact on
      therapeutic response still remains to be explored. The role of cytochrome P450
      (CYP) 3A4 in corticosteroid metabolism, and that of the glucocorticoid receptor
      (NR3C1) in regulation of responsive genes, renders CYP3A4 and NR3C1 polymorphisms
      as potential candidates for pharmacogenetic analysis. AIM: The aim of the study
      was to analyze the role of these polymorphisms in the outcome of a disease
      treated with CS drugs. METHODS: Towards this aim we analyzed the CYP3A4-290A/G
      substitution and three NR3C1 polymorphisms (200G/A, 1220A/G and BclI RFLP) in 222
      children with acute lymphoblastic leukemia (ALL) whose treatment protocols, among
      other components, contained corticosteroid drugs. RESULTS: The analysis of
      survival probabilities in relation to the indicated genotypes showed only an
      association between homozygosity for allele G of the NR3C1 BclI RFLP polymorphism
      and overall survival (univariate and multivariate hazard ratio [HR] 2.7, 95%
      confidence interval [CI] 1.0, 7.6 and 5.2, 95% CI 1.4, 18.9, respectively). The
      association reflects a correlation with disease progression and prognosis, and
      may vary depending on risk of relapse. CONCLUSION: A reduction in survival
      probability in children with ALL was associated with homozygosity for G allele of
      the NR3C1BclI RFLP polymorphism, particularly in certain patient subgroups.
      Further analysis is required to replicate this finding and to understand the
      mechanism underlying the observed association.

PMID- 15462614
TI  - Towards an ideal rowing technique for performance : the contributions from
      biomechanics.
AB  - At international standard, sculling (two oars) and rowing (one oar) are competed
      on-water over 2000 m. Race time is the critical measure of performance and is
      determined from mean skiff velocity during a race. Although a high proportion of
      race training is completed on-water, rowing ergometers are commonly used for
      performance testing, technique coaching, crew selection or for training during
      poor weather. Rowing biomechanics research has aimed to identify characteristics
      of successful sculling and sweep rowing strokes; however, biomechanical
      predictors of 2000 m rowing performance are indistinct in the literature. If
      specific biomechanical parameters distinguish between ability levels and
      successful or unsuccessful techniques, these attributes can be considered when
      modifying technique or predicting future rowing performance. The kinematics and
      kinetics of the sculling and rowing movements have been described on ergometers,
      on-water and for novice and elite male and female rowers, but there is limited
      research on the ideal technique or how a rower's anthropometry or boat set-up
      could help improve/optimise their rowing performance. Currently viewing the
      technique and providing verbal feedback is the primary tool used by a coach to
      help improve a rower's technique and performance. The greater use of customised
      telemetered sensors on the rowing skiff can assist the coach and biomechanist
      with judging when performance (skiff velocity) improves with some form of
      intervention.

PMID- 15462612
TI  - Are cardiovascular disease and osteoporosis directly linked?
AB  - For years, osteoporosis and cardiovascular disease were thought to be two
      independent consequences of aging; however, mounting evidence supports an
      association between these diseases. Recently, a widespread class of cholesterol
      lowering drugs known as statins have demonstrated (in rodents and cell cultures)
      the ability to induce bone formation. This finding is significant since current
      therapies are limited to the prevention or slowing down of bone loss rather than
      (enhancing/improving) bone formation. In humans, the ability of statins to
      generate new bone has not been consistent; however, several investigations have
      demonstrated a dramatic decrease in fracture risk. Although it has been proposed
      that statins induce new bone via increased bone morphogenetic protein-2, other
      conditions affected by statins such as dyslipidaemia, vascular calcification,
      endothelial dysfunction and impaired nitric oxide expression, may also contribute
      to the cardiovascular and bone health paradigm. Furthermore, the role of physical
      activity and its influence on cardiovascular and bone health, especially in
      postmenopausal women, may contribute to the discrepancy of findings in human
      data. In summary, it remains to be determined if statins contribute to bone
      health via improvements in vascular health or by pleiotropic properties unique to
      their pharmacology. This review provides information on our current understanding
      of the bone and cardiovascular association, as well as on novel areas of research
      to further our current understanding of these conditions.

PMID- 15462615
TI  - Incidence of injury in junior and senior rugby league players.
AB  - Rugby league is an international collision sport played at junior, amateur, semi
      professional and professional levels. Due to the high numbers of physical
      collisions and tackles, musculoskeletal injuries are common. A large percentage
      of injuries result in long-term employment and study limitations, medical costs
      and loss of income. Review articles addressing the applied physiology of rugby
      league and common rugby league injuries have been published. However, both of
      these review articles have focused on the professional rugby league player. This
      review addresses the extent of the injury problem in rugby league in all levels
      of competition (i.e. junior, amateur, semi-professional and professional). The
      incidence of rugby league injuries typically increases as the playing level is
      increased. The majority of studies have shown that the head and neck is the most
      common site of match injuries in senior rugby league players, while knee injuries
      are the most common site of injury in junior rugby league players. Muscular
      injuries are the most common type of injury sustained by senior rugby league
      players, while junior rugby league players more commonly sustain fractures.
      Injuries are most commonly sustained in tackles, by the tackled player. Thigh and
      calf strains are the most common injuries sustained during rugby league training,
      while overexertion is the most common cause of training injuries. Player fatigue
      may influence the incidence of injury, with most sub-elite (amateur and semi
      professional) rugby league injuries occurring in the second half of matches or
      the latter stages of training sessions. The majority of training injuries occur
      in the early stages of the season, while match injuries occur in the latter
      stages of the season, suggesting that changes in training and playing intensity
      may influence the incidence of injury in rugby league. Injury prevention studies
      are required to reduce the incidence, severity and cost of rugby league injuries.
      These injury prevention strategies could include coaching on defensive skills,
      correct tackling technique, correct falling technique and methods to minimise the
      absorption of impact forces in tackles. Game-specific attacking and defensive
      drills practised before and during fatigue may also encourage players to make
      appropriate decisions under fatigued conditions and apply learnt skills during
      the pressure of competitive matches. Further studies investigating risk factors
      for injury in junior and senior rugby league players, injuries sustained by
      specific playing positions and the influence of injuries on playing performance
      are warranted.

PMID- 15462613
TI  - Effects of aging on muscle fibre type and size.
AB  - Aging has been associated with a loss of muscle mass that is referred to as
      'sarcopenia'. This decrease in muscle tissue begins around the age of 50 years,
      but becomes more dramatic beyond the 60th year of life. Loss of muscle mass among
      the aged directly results in diminished muscle function. Decreased strength and
      power contribute to the high incidence of accidental falls observed among the
      elderly and can compromise quality of life. Moreover, sarcopenia has been linked
      to several chronic afflictions that are common among the aged, including
      osteoporosis, insulin resistance and arthritis. Loss of muscle fibre number is
      the principal cause of sarcopenia, although fibre atrophy--particularly among
      type II fibres--is also involved. Several physiological mechanisms have been
      implicated in the development of sarcopenia. Denervation results in the loss of
      motor units and thus, muscle fibres. A decrease in the production of anabolic
      hormones such as testosterone, growth hormone and insulin-like growth factor-1
      impairs the capacity of skeletal muscle to incorporate amino acids and synthesise
      proteins. An increase in the release of catabolic agents, specifically
      interleukin-6, amplifies the rate of muscle wasting among the elderly. Given the
      demographic trends evident in most western societies, i.e. increased number of
      those considered aged, management interventions for sarcopenia must become a
      major goal of the healthcare profession.

PMID- 15462617
TI  - Developing intuition for prices in euros: rescaling or relearning prices?
AB  - This article examines how numerical intuition for prices develops after a major
      change in currency. University students in Portugal (Study 1) and Austria (Study
      2) made price estimates for 40 different items from November 2001 to June 2002,
      surrounding the time at which these countries switched to the euro. Overall
      results are more in accordance with a relearning hypothesis, considering that
      price estimates become progressively more accurate by a process that is related
      to buying frequency and, hence, is faster for frequently bought items. An
      alternative global rescaling hypothesis received mixed support. Results also
      suggest that price estimations in euros have not yet reached a level of accuracy
      comparable with estimations in the former national currency.

PMID- 15462616
TI  - Eyewitness identification accuracy and response latency: the unruly 10-12-second
      rule.
AB  - Data are reported from 3,213 research eyewitnesses confirming that accurate
      eyewitness identifications from lineups are made faster than are inaccurate
      identifications. However, consistent with predictions from the recognition and
      search literatures, the authors did not find support for the "10-12-s rule" in
      which lineup identifications faster than 10-12 s maximally discriminate between
      accurate and inaccurate identifications (D. Dunning & S. Perretta, 2002).
      Instead, the time frame that proved most discriminating was highly variable
      across experiments, ranging from 5 s to 29 s, and the maximally discriminating
      time was often unimpressive in its ability to sort accurate from inaccurate
      identifications. The authors suggest several factors that are likely to moderate
      the 10-12-s rule.

PMID- 15462618
TI  - Confidence-accuracy calibration in absolute and relative face recognition
      judgments.
AB  - Confidence-accuracy (CA) calibration was examined for absolute and relative face
      recognition judgments as well as for recognition judgments from groups of stimuli
      presented simultaneously or sequentially (i.e., simultaneous or sequential mini
      lineups). When the effect of difficulty was controlled, absolute and relative
      judgments produced negligibly different CA calibration, whereas no significant
      difference was observed for simultaneous and sequential mini-lineups. Further,
      the effect of difficulty on CA calibration was equivalent across judgment and
      mini-lineup types. It is interesting to note that positive (i.e., old)
      recognition judgments demonstrated strong CA calibration whereas negative (i.e.,
      new) judgments evidenced little or no CA association. Implications for eyewitness
      identification are discussed.

PMID- 15462619
TI  - The influence of memory for prior instances on performance in a conflict
      detection task.
AB  - In 3 experiments, the authors examined the role of memory for prior instances for
      making relative judgments in conflict detection. Participants saw pairs of
      aircraft either repeatedly conflict with each other or pass safely before being
      tested on new aircraft pairs, which varied in similarity to the training pairs.
      Performance was influenced by the similarity between aircraft pairs. Detection
      time was faster when a conflict pair resembled a pair that had repeatedly
      conflicted. Detection time was slower, and participants missed conflicts, when a
      conflict pair resembled a pair that had repeatedly passed safely. The findings
      identify aircraft features that are used as inputs into the memory decision
      process and provide an indication of the processes involved in the use of memory
      for prior instances to make relative judgments.

PMID- 15462620
TI  - Effects of prolonged work on data entry speed and accuracy.
AB  - In 2 experiments, participants used a keyboard to enter 4-digit numbers presented
      on a computer monitor under conditions promoting fatigue. In Experiment 1,
      accuracy of data entry declined but response times improved over time, reflecting
      an increasing speed-accuracy trade-off. In Experiment 2, the (largely cognitive)
      time to enter the initial digit decreased in the 1st half but increased in the
      2nd half of the session. Accuracy and time to enter the remaining digits
      decreased across though not within session halves. The (largely motoric) time to
      press a concluding keystroke decreased over the session. Thus, through a
      combination of facilitation and inhibition, prolonged work affects the component
      cognitive and motoric processes of data entry differentially and at different
      points in practice.

PMID- 15462621
TI  - Virtually no evidence for virtually perfect time-sharing.
AB  - An examination of previous claims for virtually perfect time-sharing in dual-task
      situations reveals confounding effects that may have obscured dual-task
      interference. Two experiments are conducted in which these confounding effects
      are minimized, revealing statistically significant dual-task interference. These
      results support the hypothesis that human information processing is dominated by
      a structural central capacity limitation and call into question the hypothesis
      that dual-task interference can be eliminated by meeting the 5 conditions
      outlined by D. Meyer and D. Kieras (1999).

PMID- 15462622
TI  - Perceiving virtual geographical slant: action influences perception.
AB  - In 4 experiments, the authors varied the extent and nature of participant
      movement in a virtual environment to examine the influence of action on estimates
      of geographical slant. Previous studies showed that people consciously
      overestimate hill slant but can still accurately guide an action toward the hill
      (D. R. Proffitt, M. Bhalla, R. Gossweiler, & J. Midgett, 1995). Related studies
      suggest that one's potential to act may influence perception of slant and that
      distinct representations may independently inform perceptual and motoric
      responses. The authors found that in all conditions, perceptual judgments were
      overestimated and motoric adjustments were more accurate. The virtual environment
      allowed manipulation of the effort required to walk up simulated hills. Walking
      with the effort appropriate to the visual slant led to increased perceptual
      overestimation of slant compared with active walking with the effort appropriate
      to level ground, while visually guided actions remained accurate.

PMID- 15462623
TI  - Experience, context, and the visual perception of human movement.
AB  - Why are human observers particularly sensitive to human movement? Seven
      experiments examined the roles of visual experience and motor processes in human
      movement perception by comparing visual sensitivities to point-light displays of
      familiar, unusual, and impossible gaits across gait-speed and identity
      discrimination tasks. In both tasks, visual sensitivity to physically possible
      gaits was superior to visual sensitivity to physically impossible gaits,
      supporting perception-action coupling theories of human movement perception.
      Visual experience influenced walker-identity perception but not gait-speed
      discrimination. Thus, both motor experience and visual experience define visual
      sensitivity to human movement. An ecological perspective can be used to define
      the conditions necessary for experience-dependent sensitivity to human movement.

PMID- 15462624
TI  - Demands on attention and the role of response priming in visual discrimination of
      feature conjunctions.
AB  - This study examined how response mapping of features within single- and multiple
      feature targets affects decision-based processing and attentional capacity
      demands. Observers judged the presence or absence of 1 or 2 target features
      within an object either presented alone or with distractors. Judging the presence
      of 2 features relative to the less discriminable of these features alone was
      faster (conjunction benefits) when the task-relevant features differed in
      discriminability and were consistently mapped to responses. Conjunction benefits
      were attributed to asynchronous decision priming across attended, task-relevant
      dimensions. A failure to find conjunction benefits for disjunctive conjunctions
      was attributed to increased memory demands and variable feature-response mapping
      for 2- versus single-feature targets. Further, attentional demands were similar
      between single- and 2-feature targets when response mapping, memory demands, and
      discriminability of the task-relevant features were equated between targets.
      Implications of the findings for recent attention models are discussed.

PMID- 15462625
TI  - Adding drift to the decomposition of simple isochronous tapping: an extension of
      the Wing-Kristofferson model.
AB  - The Wing-Kristofferson model (A. M. Wing & A. B. Kristofferson, (1973a, 1973b)
      decomposes the variance of isochronous finger tapping into 2 components: a
      central clock component and a peripheral motor component. The method assumes that
      there is no drift in the intertap intervals. A new method is introduced that
      further decomposes the clock component drift and drift-free clock variance. The
      method was studied through simulation and empirical analyses. Clock variance was
      the most prominent, followed by drift, and then motor variance. Individual and
      group differences were larger for the motor and drift variances than for the
      drift-free clock variance, so that group differences observed in the past may
      have been partially due to the failure to fully remove drift. The authors argue
      that the methods presented and extensions thereon show great promise in extending
      a method in wide use since 1973.

PMID- 15462626
TI  - Contributions of oral and extraoral facial movement to visual and audiovisual
      speech perception.
AB  - Seeing a talker's face influences auditory speech recognition, but the visible
      input essential for this influence has yet to be established. Using a new
      seamless editing technique, the authors examined effects of restricting visible
      movement to oral or extraoral areas of a talking face. In Experiment 1, visual
      speech identification and visual influences on identifying auditory speech were
      compared across displays in which the whole face moved, the oral area moved, or
      the extraoral area moved. Visual speech influences on auditory speech recognition
      were substantial and unchanging across whole-face and oral-movement displays.
      However, extraoral movement also influenced identification of visual and
      audiovisual speech. Experiments 2 and 3 demonstrated that these results are
      dependent on intact and upright facial contexts, but only with extraoral movement
      displays.

PMID- 15462627
TI  - Forward and backward number translation requires conceptual mediation in both
      balanced and unbalanced bilinguals.
AB  - It is much debated whether translation is semantically mediated or based on word
      word associations at the lexical level. In 2 experiments with Dutch (L1)-French
      (L2) bilinguals, the authors showed that there is a semantic number magnitude
      effect in both forward and backward translation of number words: It takes longer
      to translate number words representing large quantities (e.g., acht, huit
      [eight]) than small quantities (e.g., twee, deux [two]). In a 3rd experiment, the
      authors replicated these effects with number words that had been acquired only
      just before the translation task. Finally, it was shown that the findings were
      not due to the restricted semantic context of the stimuli. These findings
      strongly suggest that translation processes can be semantically mediated in both
      directions, even at low levels of L2 proficiency.

PMID- 15462628
TI  - Analysis of a constraint on perception, cognition, and development: one object,
      one place, one time.
AB  - It has become increasingly common for theories to rely on a constraint that 1
      object cannot be in more than 1 place at the same time. Analysis suggests that a
      1 object-1 place-1 time constraint as literally stated is false, that a modified
      constraint is biased toward the visual modality, that it may not be a correct
      description of the physical world, is not true of how objects must appear on
      sensory surfaces, and does not mean that 2 simultaneous spatially separated
      samples must be interpreted as 2 different objects, even for vision. However,
      once such object numerosity or identity is determined in some other way, then a
      modified constraint can be used to trigger learning, such as prism adaptation. A
      far-removed implication is that "Where is an object?" may be a misleading
      question.

PMID- 15462629
TI  - Repetition blindness: out of sight or out of mind?
AB  - Does repetition blindness represent a failure of perception or of memory? In
      Experiment 1, participants viewed rapid serial visual presentation (RSVP)
      sentences. When critical words (C1 and C2) were orthographically similar, C2 was
      frequently omitted from serial report; however, repetition priming for C2 on a
      postsentence lexical decision task was equivalent whether or not C1 was similar
      to C2. In Experiment 2, participants monitored RSVP sentences for a predetermined
      target. Participants frequently failed to detect the target when it was preceded
      by an orthographically similar word. In Experiment 3, the authors investigated
      the role of the attentional blink in this effect. These experiments suggest that
      repetition blindness is a failure of conscious perception, consistent with
      predictions of the token-individuation hypothesis.

PMID- 15462631
TI  - What do letter migration errors reveal about letter position coding in visual
      word recognition?
AB  - Dividing attention across multiple words occasionally results in
      misidentifications whereby letters apparently migrate between words. Previous
      studies have found that letter migrations preserve within-word letter position,
      which has been interpreted as support for position-specific letter coding. To
      investigate this issue, the authors used word pairs like STEP and SOAP, in which
      a letter in 1 word could migrate to an adjacent letter in another word to form an
      illusory word (STOP). Three experiments show that both same-position and adjacent
      position letter migrations can occur, as well as migrations that cross 2 letter
      positions. These results argue against position-specific letter coding schemes
      used in many computational models of reading, and they provide support for coding
      schemes based on relative rather than absolute letter position.

PMID- 15462632
TI  - Control over the time course of cognition in the tempo-naming task.
AB  - Five experiments are reported in which standard naming and tempo-naming tasks
      were used to investigate mechanisms of control over the time course of lexical
      processing. The time course of processing was manipulated by asking participants
      to time their responses with an audiovisual metronome. As the tempo of the
      metronome increased, results showed that (a) the rate of lexical errors
      increased, whereas the rate of regularization errors remained constant; (b) onset
      errors increased at a faster rate than body errors; (c) stimulus effects weakened
      on latencies, whereas they strengthened on durations and errors; and (d) naming
      durations decreased more slowly when stimuli were presented prior to the response
      cue. These results constitute evidence that time pressure in the tempo-naming
      task caused a compression in the time course of lexical processing. Compression
      is discussed in terms of threshold mechanisms and rate mechanisms of control.

PMID- 15462633
TI  - The role of melodic and temporal cues in perceiving musical meter.
AB  - A number of different cues allow listeners to perceive musical meter. Three
      experiments examined effects of melodic and temporal accents on perceived meter
      in excerpts from folk songs scored in 6/8 or 3/4 meter. Participants matched
      excerpts with 1 of 2 metrical drum accompaniments. Melodic accents included
      contour change, melodic leaps, registral extreme, melodic repetition, and
      harmonic rhythm. Two experiments with isochronous melodies showed that contour
      change and melodic repetition predicted judgments. For longer melodies in the 2nd
      experiment, variables predicted judgments best at the beginning of excerpts. The
      final experiment, with rhythmically varied melodies, showed that temporal
      accents, tempo, and contour change were the strongest predictors of meter. The
      authors' findings suggest that listeners combine multiple melodic and temporal
      features to perceive musical meter.

PMID- 15462634
TI  - Face recognition is affected by similarity in spatial frequency range to a
      greater degree than within-category object recognition.
AB  - Previous studies have suggested that face identification is more sensitive to
      variations in spatial frequency content than object recognition, but none have
      compared how sensitive the 2 processes are to variations in spatial frequency
      overlap (SFO). The authors tested face and object matching accuracy under varying
      SFO conditions. Their results showed that object recognition was more robust to
      SFO variations than face recognition and that the vulnerability of faces was not
      due to reliance on configural processing. They suggest that variations in
      sensitivity to SFO help explain the vulnerability of face recognition to changes
      in image format and the lack of a middle-frequency advantage in object
      recognition.

PMID- 15462635
TI  - The nature of change detection and online representations of scenes.
AB  - This article provides evidence for implicit change detection and for the
      contribution of multiple memory sources to online representations. Multiple eye
      movement measures distinguished original from changed scenes, even when college
      students had no conscious awareness for the change. Patients with amnesia showed
      a systematic deficit on 1 class of eye-movement measures of change detection,
      even though conscious awareness was not required for the effect to be observed.
      The authors' findings suggest that online representations of scenes are (a) built
      up across viewings, (b) composed of activated information from both long-term and
      working memory, and (c) directly compared with currently processed information
      regarding the external world. Subsequent online processing is influenced by these
      representations even when the results of the comparison are not accessible for
      verbal report.

PMID- 15462636
TI  - Suicide and mental health in rural, remote and metropolitan areas in Australia.
AB  - OBJECTIVES: To compare the prevalence of mental health disorders and the use of
      professional help by area of residence, age and sex; and to determine whether the
      differences parallel differences in suicide rates. DESIGN: Retrospective cross
      sectional analysis of Australian national mortality data (1997-2000) and the
      National Survey of Mental Health and Wellbeing (1997), using broad area-of
      residence classifications based on the Rural, Remote and Metropolitan Area (RRMA)
      index. MAIN OUTCOME MEASURES: (a) Suicide rates; (b) prevalence of depression,
      anxiety and substance-use disorders; and (c) use of health professionals for
      mental health problems - by age, sex and area of residence. RESULTS: Higher
      suicide rates were evident for men, particularly young men in rural (40.4 per 100
      000; z, 3.2) and remote (51.7 per 100 000; z, 7.2) populations compared with
      metropolitan (31.8 per 100 000) populations. Although the proportion of young men
      reporting mental health disorders did not differ significantly between rural
      (23.5%; z, -0.5) and remote (18.8%; z, -1.6) areas compared with metropolitan
      (25.6%) areas, young men with a mental health disorder from non-metropolitan
      areas were significantly less likely than those from metropolitan areas to seek
      professional help for a mental health disorder (11.4% v 25.2%; z, -2.2).
      CONCLUSIONS: There is a need to investigate why young men in non-metropolitan
      areas, the population with the greatest suicide risk, do and do not engage with
      mental health services.

PMID- 15462637
TI  - General practitioners' response to depression and anxiety in the Australian
      community: a preliminary analysis.
AB  - OBJECTIVES: To examine the uptake by general practitioners (GPs) of the five key
      components of the Better Outcomes in Mental Health Care (BOiMHC) initiative:
      education and training for GPs; the three-step mental health process; focussed
      psychological strategies; access to allied health services; and access to
      psychiatrist support. SETTING: All Australian states and territories during the
      first 15 months of the initiative (1 July 2002 - 30 September 2003). DESIGN:
      Retrospective survey of de-identified registration data held by the General
      Practice Mental Health Standards Collaboration (training uptake), de-identified
      Health Insurance Commission (HIC) billing data (provision of the three-step
      mental health process, focussed psychological strategies and case conferences
      with psychiatrists), and reports from "access to allied health services" projects
      to the Australian Department of Health and Ageing (project participation). MAIN
      OUTCOME MEASURES: Number and percentage of Australian GPs certified as eligible
      to participate in the initiative; provision of the three-step mental health
      process and focussed psychological strategies by GPs; participation in allied
      health pilot projects; and access to psychiatrist support. RESULTS: Within 15
      months of the BOiMHC initiative commencing, 3046 GPs (about 15% of Australian
      GPs) had been certified as eligible to participate, including 387 who had
      registered to provide focussed psychological strategies. GPs had completed 11 377
      three-step mental health processes and 6472 sessions of focussed psychological
      strategies. Sixty-nine "access to allied health services" projects had been
      funded, with the original 15 pilot projects enabling 346 GPs to refer 1910
      consumers to 134 individual allied health professionals and 10 agencies. In
      contrast, the "access to psychiatrist support" component was less successful,
      with the HIC billed for 62 case conferences at which a psychiatrist and a GP were
      present. CONCLUSION: The level of uptake of the main components of the BOiMHC
      initiative has expanded the national capacity to respond to the needs of people
      with common mental disorders, such as depression and anxiety.

PMID- 15462638
TI  - Making new choices about antidepressants in Australia: the long view 1975-2002.
AB  - OBJECTIVE: To examine trends in types of antidepressant medications prescribed in
      Australia between 1975 and 2002. DESIGN: Sales data from the Australian
      pharmaceutical industry were used to examine trends in overall antidepressant
      prescribing and changes in the types of antidepressants prescribed between 1975
      and 2002. MAIN OUTCOME MEASURES: Antidepressant sales were expressed as defined
      daily doses (DDDs) per 1000 people per day, using the estimated Australian
      population for each year obtained from the Australian Bureau of Statistics.
      RESULTS: Average annual growth in the sales of antidepressants was 1.1% per year
      from 1975 to 1990, after which growth rose steeply to reach 29% in 1995. By 2002
      the rate of growth had slowed to 6.6%. Eighty per cent of total sales were
      accounted for by four drugs in 1975, 1980 and 1985; five in 1990; seven drugs in
      1995 and 2000; and six drugs in 2001 and 2002. CONCLUSIONS: The rapid growth in
      antidepressant prescribing that was characteristic of the early 1990s, and
      reflected the emergence of new classes of agents, did not continue into the late
      1990s. Selective serotonin reuptake inhibitors now dominate antidepressant
      prescribing in Australia.

PMID- 15462639
TI  - Overdose in young people using heroin: associations with mental health,
      prescription drug use and personal circumstances.
AB  - OBJECTIVE: To identify patterns of mental health, prescription drug use and
      personal circumstances associated with heroin overdose in young people. DESIGN:
      Linkage of data on use of Pharmaceutical Benefits Scheme (PBS) prescription drugs
      with data from a self-report questionnaire. SETTING: Inner metropolitan
      Melbourne, Australia. SUBJECTS: 163 young people, 15-30 years, using heroin. MAIN
      OUTCOME MEASURES: Personal circumstances, mental health (as measured by various
      scales), and PBS-listed prescription drug use. RESULTS: Young people using heroin
      reported high rates of feelings of hopelessness, depression, antisocial
      behaviour, self-harm and diagnosed mental illness. A prior history of overdose
      was associated with previous mental illness, which in turn was associated with
      being female, having poor social support, being dissatisfied with relationships,
      and living alone or in temporary accommodation. While feelings of hopelessness
      and antisocial behaviour were strongly associated with overdose history, the
      number of PBS prescription drugs used had a very strong relationship with
      overdose, particularly benzodiazepines, other opioids, tricyclic antidepressants
      and tranquillisers. CONCLUSIONS: Further research to explore causal relationships
      between prescription drugs and heroin overdose is warranted. Improved data
      linkage to PBS records for general practitioners may facilitate safer prescribing
      practices.

PMID- 15462640
TI  - Effectiveness of complementary and self-help treatments for anxiety disorders.
AB  - OBJECTIVES: To review the evidence for the effectiveness of complementary and
      self-help treatments for anxiety disorders. DATA SOURCES: Systematic literature
      search using PubMed, PsycLit, and the Cochrane Library. DATA SYNTHESIS: 108
      treatments were identified and grouped under the categories of medicines and
      homoeopathic remedies, physical treatments, lifestyle, and dietary changes. We
      give a description of the 34 treatments (for which evidence was found in the
      literature searched), the rationale behind the treatments, a review of studies on
      effectiveness, and the level of evidence for the effectiveness studies.
      CONCLUSIONS: The treatments with the best evidence of effectiveness are kava (for
      generalised anxiety), exercise (for generalised anxiety), relaxation training
      (for generalised anxiety, panic disorder, dental phobia and test anxiety) and
      bibliotherapy (for specific phobias). There is more limited evidence to support
      the effectiveness of acupuncture, music, autogenic training and meditation for
      generalised anxiety; for inositol in the treatment of panic disorder and
      obsessive-compulsive disorder; and for alcohol avoidance by people with alcohol
      use disorders to reduce a range of anxiety disorders.

PMID- 15462641
TI  - Reducing the burden of depression: are we making progress in Australia?

PMID- 15462642
TI  - Experience with treatment services for people with bipolar disorder.
AB  - OBJECTIVE: To describe the experiences of people with bipolar disorder with
      primary care and specialist mental health services. DESIGN AND SETTING: Focus
      groups and indepth interviews were conducted in seven Australian capital cities
      between July 2002 and April 2003. Thematic analyses were conducted using the QSR
      NUD*IST software package for qualitative data. PARTICIPANTS: Forty-nine people
      with bipolar disorder participated in the focus groups and four participated in
      the interviews. RESULTS: Thematic analyses highlighted eight key themes. Most
      notably, respondents identified a lack of awareness and understanding about
      bipolar disorder within the Australian community, which contributed to apparent
      delays in seeking medical assessment. The burden of illness was exacerbated by
      difficulties experienced with obtaining an accurate diagnosis and optimal
      treatment. The healthcare system responses were described as inadequate and
      included inappropriate crisis management, difficulties accessing hospital care,
      inappropriate exclusion of carers and families from management decisions, and
      frequent discontinuities of medical and psychological care. CONCLUSIONS: People
      with extensive experience of bipolar disorder report barriers to optimal care
      because of lack of community understanding and healthcare system shortcomings.
      These barriers exacerbate the social, interpersonal and economic costs of this
      illness.

PMID- 15462643
TI  - A National Depression Index for Australia.
AB  - OBJECTIVE: To develop a National Depression Index for measuring the depression
      status of the Australian population. DESIGN: Cross-sectional data were analysed
      from two random samples of the Australian adult population - the National Survey
      of Mental Health and Wellbeing (2000) and the National Health Survey (2001).
      PARTICIPANTS: The National Survey of Mental Health and Wellbeing (2000) - 10 641
      participants; and the National Health Survey (2001) - 17 918 participants. MAIN
      OUTCOME MEASURES: Selected items from the Kessler Psychological Distress Scale
      (K10); and diagnoses of a major depressive episode according to DSM-IV criteria
      using a computerised interview. RESULTS: Six items from the K10 that were most
      closely related to the DSM-IV diagnosis of "major depressive episode" were
      identified. Scores on an index calculated from these items were rescaled to form
      an index reflecting relative risk of depression and having a value of 100 for the
      Australian adult population. Taking into account sex, employment status and
      income, index values were higher in younger people, females, unemployed people
      and those socioeconomically disadvantaged. This pattern provides additional
      support for the validity of the index, as well as establishing benchmark levels
      to which index values from future surveys and in other groups may be compared.
      CONCLUSIONS: The proposed National Depression Index is a valid indicator of
      depression and level of depressive symptoms. It is suitable for monitoring
      depression at the population level. The scaling characteristics of the measure
      ensure that it can be interpreted by members of the general public.

PMID- 15462644
TI  - How much more can we lose?": carer and family perspectives on living with a
      person with depression.
AB  - OBJECTIVE: To explore the experiences of carers and families of people with
      depression. DESIGN AND SETTING: Structured focus groups conducted in six
      Australian capital cities between February 2002 and July 2002. Thematic analyses
      were conducted using the QSR NUD*IST software package for qualitative data.
      PARTICIPANTS: Thirty-seven carers or family members. RESULTS: Thematic analyses
      highlighted five key themes. Most notably, the carer's role is made more
      difficult by the lack of community awareness about depression, and, in some
      instances, an unwillingness of other family and friends to provide ongoing
      support. Carers experience a resulting sense of isolation, often exacerbated by
      adverse experiences with healthcare providers. Carers and family members are
      frequently excluded when key decisions are made, and report that emergency
      services are relatively unresponsive to their concerns. By contrast, community
      support organisations usually provided a sense of inclusion and common purpose.
      CONCLUSIONS: The experiences of carers and families of people with depression
      highlight the urgent need for more extensive community education about the
      illness and more productive collaboration within the healthcare system.

PMID- 15462645
TI  - Doctors' health and wellbeing: taking up the challenge in Australia.
AB  - Promoting psychological wellness in doctors requires tailored interventions.

PMID- 15462646
TI  - Understanding the stresses and strains of being a doctor.
AB  - Stress in doctors is a product of the interaction between the demanding nature of
      their work and their often obsessive, conscientious and committed personalities.
      In the face of extremely demanding work, a subjective lack of control and
      insufficient rewards are powerful sources of stress in doctors. If demands
      continue to rise and adjustments are not made, then inevitably a "correction"
      will occur, which may take the form of "burnout" or physical and/or mental
      impairment. Doctors need to reclaim control of their work environment and
      employers need to recognise the need for doctors to participate in decisions
      affecting their working lives. All doctors should be aware of predictors of risk
      and signals of impairment, as well as available avenues of assistance. Relevant
      medical organisations (eg, the Colleges, hospital administrations, and medical
      defence organisations) need to develop and rehearse effective response pathways
      for assisting impaired doctors.

PMID- 15462647
TI  - The thin line.

PMID- 15462649
TI  - Burnout and psychiatric morbidity in new medical graduates.
AB  - OBJECTIVE: To determine the prevalence of psychiatric morbidity and burnout in
      final-year medical students, and changes in these measures during the intern
      year. DESIGN: Prospective longitudinal cohort study over 18 months, with
      assessment of psychiatric morbidity and burnout on six occasions. PARTICIPANTS:
      All 117 students in the first graduating cohort of the University of Sydney
      Graduate Medical Program were invited to participate in the study; 110 consented.
      OUTCOME MEASURES: Psychiatric morbidity assessed with the 28-item General Health
      Questionnaire and burnout assessed with the Maslach Burnout Inventory. RESULTS:
      The point prevalence of participants meeting criteria for psychiatric morbidity
      and burnout rose steadily throughout the study period. CONCLUSIONS: Internship
      remains a stressful time for medical graduates, despite initiatives to better
      support them during this period. The implications for the doctors themselves and
      for the communities they serve warrant further attention, including programs
      specifically aimed at reducing the rate of psychological morbidity and burnout
      during internship.

PMID- 15462650
TI  - Balancing work, family and other lifestyle aspects: a qualitative study of
      Australian medical students' attitudes.
AB  - OBJECTIVE: To explore the attitudes of Australian medical students to the balance
      between work, family and other aspects of lifestyle, within a broader exploration
      of the issues that they regard as important to their decisions about future
      career. DESIGN: Qualitative study using semistructured focus groups and
      individual interviews. SETTING: The three medical schools in New South Wales and
      a national conference for students interested in rural practice. PARTICIPANTS:
      First- and final-year medical students who volunteered for focus groups held
      between March and August 2002 (82 students in 10 groups) or for individual
      interviews held between July and December 2003 (48 students). MAIN OUTCOME
      MEASURES: Emergent themes relating to the balance of work, family and other
      aspects of lifestyle. RESULTS: Most students referred to a balance of work,
      family and lifestyle as an important factor in their career decisions. While
      indicating they were committed to medicine, they were unwilling to work to the
      exclusion of all else. Most saw family commitments as a high priority, and many
      saw "time out" as important in maintaining their health. Female students spoke of
      part-time work as essential for future happiness, while some male students
      expressed a preference for working part-time. They would seek to achieve balance
      by choosing to work in disciplines, locations and structures where limited-hours
      work is available, and would negotiate support from their partners and parents in
      caring for children. CONCLUSIONS: It is important that the medical profession
      continue to develop working and training structures that allow a balance of work,
      family and lifestyle.

PMID- 15462651
TI  - A call for community values in medical institutions.

PMID- 15462652
TI  - Surgeon, test (and heal) thyself: sharps injuries and hepatitis C risk.
AB  - Sharps injuries experienced by surgeons are common, but are under-recognised and
      under-reported. The overall risks of transmission of blood-borne viruses to
      surgeons are low, with hepatitis C posing the greatest transmission risk. Recent
      trials show that early treatment of acute hepatitis C results in a cure rate
      approaching 100%. Surgeons and theatre staff should be encouraged to report and
      follow up sharps injuries to allow early detection and treatment. Additionally,
      because exposures to blood-borne viruses may be unrecognised, surgeons should
      have regular tests for blood-borne viruses. There should be no restriction of
      practice in the "window period" between potential exposure and obtaining results
      of testing, because of the overall low risk of transmission.

PMID- 15462653
TI  - Doctors do not adequately look after their own physical health.
AB  - Studies of doctors' health have emphasised psychological health, and limited data
      have been collected on their physical health status. Doctors often fail to follow
      current preventive health guidelines for their physical health. About half of
      doctors do not have an established relationship with an independent general
      practitioner. This would enhance their health and provide a means of ready access
      to the healthcare system should a problem arise.

PMID- 15462655
TI  - Coeliac disease: the great imitator.

PMID- 15462656
TI  - Critical decision points in the management of impaired doctors: the New South
      Wales Medical Board program.
AB  - The New South Wales Medical Board has developed the Impaired Registrants Program
      to deal with impaired registrants (doctors and medical students) in a
      constructive and non-disciplinary manner; the program is now well established.
      The Program enables the Board to protect the public, while maintaining doctors in
      practice whenever possible. Disorders that commonly lead to referral of impaired
      doctors include alcohol and drug misuse, major depression, bipolar disorder,
      cognitive impairment and, less commonly, psychotic and personality disorders and
      anorexia nervosa. Pathways in the program are individualised according to the
      impact of the specific disorder, the registrant's career stage, stage of
      involvement in the program, insight and motivation. Critical points in the
      program include entry, easing of conditions, breach of conditions, return to work
      after suspension, and exit from the program. Decision-making at these points
      takes into account the nature of the impairment, compliance, professional and
      personal support available and the registrant's insight and motivation.

PMID- 15462657
TI  - The Victorian Doctors Health Program: the first 3 years.
AB  - The Victorian Doctors Health Program (VDHP) was established in November 2000 to
      provide a confidential and compassionate service for doctors and medical students
      with health concerns, including alcohol, other drug and mental health problems.
      Although funded by the Medical Practitioners Board of Victoria, the VDHP is
      completely independent of the Board. Its staff include a director with experience
      of North American Physician Health Programs and a case manager/psychologist. In
      its first 3 years of operation, the VDHP had 438 contacts: 218 requests for
      advice and information, and 220 contacts resulting in provision of services (to
      92 doctors and students with alcohol or other drug problems, 82 with psychiatric
      problems, and 40 with stress-related or emotional problems). 99 participants
      received standard care (assessment, referral and up to two consultations with the
      program) and 56 extended care (three or more consultations with the program). 65
      participants (most with substance use disorder) entered the more intensive Case
      Management, Aftercare and Monitoring Program (CAMP); 57 of these have had
      outcomes considered satisfactory, with 50 returned to work.

PMID- 15462658
TI  - Crossing professional boundaries in medicine: the slippery slope to patient
      sexual exploitation.
AB  - While some cases of sexual exploitation involve predatory doctors, many other
      cases represent the culmination of a series of boundary crossings (non
      exploitative departures from usual practice). The deliberate move to reduce
      formality in medicine has increased the likelihood of boundary crossings and
      violations. There are also individual doctor risk factors; boundary violations
      appear more likely when doctors are under stress, with insufficient emotional
      support. Preventive strategies include continuing education about ethics and the
      management of professional boundaries, along with appropriate psychological
      support structures for doctors. Doctors are often involved in other professional
      relationships as teachers, supervisors and team leaders; inappropriate sexual
      behaviour in these relationships is harassment. Public pressure for more punitive
      responses is likely if the profession is not seen to be doing all it can to deal
      with these issues effectively, and to be cooperating with other responsible
      agencies.

PMID- 15462659
TI  - The personal cost of medical litigation.

PMID- 15462660
TI  - An invisible workforce?

PMID- 15462661
TI  - Canada responds: an explosion in doctors' health awareness, promotion and
      intervention.

PMID- 15462662
TI  - Services for sick doctors in the UK.

PMID- 15462663
TI  - Physicians' health programs--what's happening in the USA?

PMID- 15462664
TI  - Medical marriages and other intimate relationships.
AB  - Marital challenges are ubiquitous in the relationships of doctors. Common issues
      include overwork, a need for control, self-neglect, perceived and felt stigma,
      being a "wounded healer", trouble with boundaries, chemical dependency,
      depression, and more. Knowing the hallmarks of a healthy relationship,
      recognising warning signals of trouble, and taking action through suggested
      strategies can be salutary.

PMID- 15462666
TI  - Staying human in the medical family: the unique role of doctor-parents.
AB  - Issues confronting doctor-parents include the impact of parenting on career
      choice, special challenges faced by women doctor-parents, leave entitlements, and
      the unique strengths and challenges of two-doctor families. Experience from one
      Canadian doctors' health program suggests that unique themes include
      communication within doctor-families, insight into doctor-parent dynamics, the
      relationship between doctor-parents and their child's doctor, and potential
      boundary crossings and violations within the doctor-family. The relationships
      between medical workforce sustainability, medical human resources, and issues
      related to doctor-parents need further consideration and analysis.

PMID- 15462667
TI  - Helping addicted colleagues.

PMID- 15462668
TI  - The black hole of depression: a personal perspective.

PMID- 15462669
TI  - Diabetes, my constant companion.

PMID- 15462670
TI  - Neural stem cells and cell replacement therapy: making the right cells.
AB  - The past few years have seen major advances in the field of NSC (neural stem
      cell) research with increasing emphasis towards its application in cell
      replacement therapy for neurological disorders. However, the clinical application
      of NSCs will remain largely unfeasible until a comprehensive understanding of the
      cellular and molecular mechanisms of NSC fate specification is achieved. With
      this understanding will come an increased possibility to exploit the potential of
      stem cells in order to manufacture transplantable NSCs able to provide a safe and
      effective therapy for previously untreatable neurological disorders. Since the
      pathology of each of these disorders is determined by the loss or damage of a
      specific neural cell population, it may be necessary to generate a range of NSCs
      able to replace specific neurons or glia rather than generating a generic NSC
      population. Currently, a diverse range of strategies is being investigated with
      this goal in mind. In this review, we focus on the relationship between NSC
      specification and differentiation and discuss how this information may be used to
      direct NSCs towards a particular fate.

PMID- 15462671
TI  - Syncollin is required for efficient zymogen granule exocytosis.
AB  - Syncollin is a 13 kDa protein that is present in the exocrine pancreas, where the
      majority of the protein is tightly attached to the luminal surface of the zymogen
      granule membrane. We have addressed the physiological role of syncollin by
      studying the phenotype of syncollin KO (knockout) mice. These mice show
      pancreatic hypertrophy and elevated pancreatic amylase levels. Further,
      secretagogue-stimulated amylase release from pancreatic lobules of syncollin KO
      mice was found to be reduced by about 45% compared with wild-type lobules, and
      the delivery of newly synthesized protein to zymogen granules was delayed,
      indicating that the mice have a pancreatic secretory defect. As determined by two
      photon imaging, the number of secretagogue-stimulated exocytotic events in acini
      from syncollin KO mice was reduced by 50%. This reduction was accounted for
      predominantly by a loss of later, 'secondary' fusion events between zymogen
      granules and other granules that had already fused with the plasma membrane. We
      conclude that syncollin is required for efficient exocytosis in the pancreatic
      acinar cell, and that it plays a particularly important role in compound
      exocytosis.

PMID- 15462672
TI  - A simple promoter containing two Sp1 sites controls the expression of sterol
      regulatory-element-binding protein 1a (SREBP-1a).
AB  - The mammalian gene for SREBP-1 (sterol-regulatory-element-binding protein 1)
      contains two promoters that control the production of two proteins, SREBP-1a and 
      1c, and each contains a unique N-terminal transcriptional activation domain, but
      they are otherwise identical. The relative level of each mRNA varies from tissue
      to tissue and they respond differently to regulatory stimuli. SREBP-1c is more
      abundantly expressed in liver, where its level is also regulated by insulin and
      liver X receptor activators, and it is also autoregulated by SREBPs. In contrast,
      SREBP-1a mRNA levels are relatively low and constant in different tissues and few
      studies have specifically analysed its pattern of expression and regulation. In
      the present study, we show that the promoter for SREBP-1a is contained in a very
      small promoter-proximal region containing two Sp1 sites. The small and relatively
      simple structure for its promoter provides an explanation for the low level of
      SREBP-1a expression. Additionally, since Sp1 has been implicated in the modest
      regulation of several genes by insulin, its involvement in the expression of the
      SREBP-1a promoter provides an explanation for the modest insulin regulation
      observed in animal experiments.

PMID- 15462674
TI  - Diagnostic polymorphisms in the mitochondrial cytochrome b gene allow
      discrimination between cattle, sheep, goat, roe buck and deer by PCR-RFLP.
AB  - BACKGROUND: As an alternative to direct DNA sequencing of PCR products, random
      PCR-RFLP is an efficient technique to discriminate between species. The PCR-RFLP
      method is an inexpensive tool in forensic science, even if the template is
      degraded or contains only traces of DNA from various species. RESULTS:
      Interspecies-specific DNA sequence polymorphisms in the mitochondrial cytochrome
      b gene were analyzed using PCR-RFLP technology to determine the source (i.e.,
      species) of blood traces obtained from a leaf. CONCLUSIONS: The method presented
      can be used for the discrimination of cattle (Bos taurus), sheep (Ovis aries),
      goat (Capra hircus), roe buck (Capreolus capreolus) and red deer (Cervus
      elaphus).

PMID- 15462675
TI  - Emphysematous cystitis: an unusual disease of the Genito-Urinary system suspected
      on imaging.
AB  - Emphysematous cystitis is a rare disease entity caused by gas fermenting
      bacterial and fungal pathogens. Clinical symptoms are nonspecific and diagnostic
      clues often arise from the unanticipated imaging findings. We report a case of 52
      year-old male who presented with fever, dysuria and gross hematuria who was found
      to have emphysematous cystitis.

PMID- 15462673
TI  - The expression of the human neuronal alpha3 Na+,K+-ATPase subunit gene is
      regulated by the activity of the Sp1 and NF-Y transcription factors.
AB  - The Na+,K+-ATPase is a ubiquitous protein found in virtually all animal cells
      which is involved in maintaining the electrochemical gradient across the plasma
      membrane. It is a multimeric enzyme consisting of alpha, beta and gamma subunits
      that may be present as different isoforms, each of which has a tissue-specific
      expression profile. The expression of the Na+,K+-ATPase alpha3 subunit in humans
      is confined to developing and adult brain and heart, thus suggesting that its
      catalytic activity is strictly required in excitable tissues. In the present
      study, we used structural, biochemical and functional criteria to analyse the
      transcriptional mechanisms controlling the expression of the human gene in
      neurons, and identified a minimal promoter region of approx. 100 bp upstream of
      the major transcription start site which is capable of preferentially driving the
      expression of a reporter gene in human neuronal cell lines. This region contains
      the cognate DNA sites for the transcription factors Sp1/3/4 (transcription
      factors 1/3/4 purified from Sephacryl and phosphocellulose columns), NF-Y
      (nuclear factor-Y) and a half CRE (cAMP-response element)-like element that binds
      a still unknown protein. Although the expression of these factors is not tissue
      specific, co-operative functional interactions among them are required to direct
      the activity of the promoter predominantly in neuronal cells.

PMID- 15462676
TI  - Tracking of physical activity, fitness, body composition and diet from
      adolescence to young adulthood: The Young Hearts Project, Northern Ireland.
AB  - BACKGROUND: The assumption that lifestyles formed early in life track into
      adulthood has been used to justify the targeting of health promotion programmes
      towards children and adolescents. The aim of the current study was to use data
      from the Northern Ireland Young Hearts Project to ascertain the extent of
      tracking, between adolescence and young adulthood, of physical activity, aerobic
      fitness, selected anthropometric variables, and diet. METHODS: Males (n 245) and
      females (n 231) were assessed at age 15 y, and again in young adulthood [mean
      (SD) age 22 (1.6) y]. At both timepoints, height, weight and skinfold thicknesses
      were measured, and physical activity and diet were assessed by questionnaire and
      diet history method respectively. At 15y, fitness was assessed using the 20 metre
      shuttle run, while at young adulthood, the PWC170 cycle ergometer test was used.
      For each measurement made at 15y, subjects were ranked into 'low' (L1; lowest
      25%), 'medium' (M1; middle 50%) or 'high' (H1; highest 25%) categories. At young
      adulthood, similar categories (L2, M2, H2) were created. The extent of tracking
      of each variable over time was calculated using 3 x 3 matrices constructed using
      these two sets of categories, and summarised using kappa (kappa) statistics.
      RESULTS: Tracking of diet and fitness was poor (kappa </= 0.20) in both sexes,
      indicating substantial drift of subjects between the low, medium and high
      categories over time. The tracking of physical activity in males was fair (kappa
      0.202), but was poor in females (kappa 0.021). In contrast, anthropometric
      variables such as weight, body mass index and sum of skinfolds tracked more
      strongly in females (kappa 0.540, kappa 0.307, kappa 0.357 respectively) than in
      males (kappa 0.337, kappa 0.199, kappa 0.216 respectively). CONCLUSIONS: The poor
      tracking of fitness and diet in both sexes, and physical activity in females,
      suggests that these aspects of adolescent lifestyle are unlikely to be predictive
      of behaviours in young adulthood. In contrast, the fair to moderate tracking of
      anthropometric variables, particularly in females, suggests that attempts to
      reduce the ever increasing incidence of overweight and obesity in adults, should
      probably begin in earlier life.

PMID- 15462677
TI  - Effect of smoking on vitamin A, vitamin E, and other trace elements in patients
      with cardiovascular disease in Bangladesh: a cross-sectional study.
AB  - BACKGROUND: Data regarding the impact of cigarette smoking on trace elements are
      scarce and inconsistent. In this study, we evaluated the effect of smoking on
      serum concentrations of trace elements among adult males with heart disease.
      METHODS: This cross-sectional study included 100 adults hospitalized with heart
      disease in Bangladesh. The major variables of interest included mean serum
      concentrations of trace elements and proportion of subjects with bacterial growth
      on throat swab culture. RESULTS: Smokers had significantly lower serum
      concentrations of retinol, alpha-tocopherol, selenium, and zinc and increased
      concentrations of copper. Throat swab cultures were more often positive for
      Streptococcus beta-hemolyticus in smokers than controls. CONCLUSIONS: Smoking
      decreases serum concentrations of trace elements. Smoking control programs are
      needed in Bangladesh to improve health and nutrition of the people who are
      already nutritionally deficient.

PMID- 15462678
TI  - Reduced proviral loads during primo-infection of sheep by Bovine Leukemia virus
      attenuated mutants.
AB  - BACKGROUND: The early stages consecutive to infection of sheep (e.g. primo
      infection) by Bovine leukemia virus mutants are largely unknown. In order to
      better understand the mechanisms associated with this period, we aimed at
      analyzing simultaneously three parameters: B-lymphocytosis, cell proliferation
      and viral replication. RESULTS: Sheep were experimentally infected either with a
      wild type BLV provirus or with selected mutants among which: a virus harboring an
      optimalized LTR promoter with consensus cyclic AMP-responsive elements, two
      deletants of the R3 or the G4 accessory genes and a fusion-deficient
      transmembrane recombinant. Seroconversion, as revealed by the onset of an anti
      viral antibody response, was detected at 3 to 11 weeks after inoculation. At
      seroconversion, all sheep exhibited a marked increase in the numbers of
      circulating B lymphocytes expressing the CD5 and CD11b cluster of differentiation
      markers and, interestingly, this phenomenon occurred independently of the type of
      virus. The net increase of the absolute number of B cells was at least partially
      due to accelerated proliferation as revealed, after intravenous injection of
      bromodeoxyuridine, by the higher proportion of circulating BrdU+ B lymphocytes.
      BLV proviral DNA was detected by polymerase chain reaction in the leucocytes of
      all sheep, as expected. However, at seroconversion, the proviral loads were lower
      in sheep infected by the attenuated proviruses despite similar levels of B cell
      lymphocytosis. CONCLUSIONS: We conclude that the proviral loads are not directly
      linked to the extent of B cell proliferation observed during primo-infection of
      BLV-infected sheep. We propose a model of opportunistic replication of the virus
      supported by a general activation process of B lymphocytes.

PMID- 15462679
TI  - Perceived personal, social and environmental barriers to weight maintenance among
      young women: A community survey.
AB  - BACKGROUND: Young women are a group at high risk of weight gain. This study
      examined a range of perceived personal, social and environmental barriers to
      physical activity and healthy eating for weight maintenance among young women,
      and how these varied by socioeconomic status (SES), overweight status and
      domestic situation. METHODS: In October-December 2001, a total of 445 women aged
      18-32 years, selected randomly from the Australian electoral roll, completed a
      mailed self-report survey that included questions on 11 barriers to physical
      activity and 11 barriers to healthy eating (relating to personal, social and
      environmental factors). Height, weight and socio-demographic details were also
      obtained. Statistical analyses were conducted mid-2003. RESULTS: The most common
      perceived barriers to physical activity and healthy eating encountered by young
      women were related to motivation, time and cost. Women with children were
      particularly likely to report a lack of social support as an important barrier to
      physical activity, and lack of social support and time as important barriers to
      healthy eating. Perceived barriers did not differ by SES or overweight status.
      CONCLUSIONS: Health promotion strategies aimed at preventing weight gain should
      take into account the specific perceived barriers to physical activity and
      healthy eating faced by women in this age group, particularly lack of motivation,
      lack of time, and cost. Strategies targeting perceived lack of time and lack of
      social support are particularly required for young women with children.

PMID- 15462680
TI  - Electroesophagogram in gastroesophageal reflux disease with a new theory on the
      pathogenesis of its electric changes.
AB  - BACKGROUND: In view of the disturbed esophageal peristaltic activity and abnormal
      esophageal motility in gastroesophageal reflux disease, (GERD), we investigated
      the hypothesis that these changes result from a disordered myoelectric activity
      of the esophagus. METHODS: The electric activity of the esophagus
      (electroesophagogram, EEG) was studied in 27 patients with GERD (16 men, 11
      women, mean age 42.6 +/- 5.2 years) and 10 healthy volunteers as controls (6 men,
      4 women, mean age 41.4 +/- 4.9 years). According to the Feussner scoring system,
      7 patients had a mild (score 1), 10 a moderate (score 2) and 10 a severe (score
      3) stage of the disease. One electrode was applied to the upper third and a
      second to the lower third of the esophagus, and the electric activity was
      recorded. The test was repeated after the upper electrode had been moved to the
      mid-esophagus. RESULTS: The EEG of the healthy volunteers showed slow waves and
      exhibited the same frequency, amplitude and conduction velocity from the 2
      electrodes of the individual subject, regardless of their location in the upper,
      middle or lower esophagus. Action potentials occurred randomly. In GERD patients,
      score 1 exhibited electric waves' variables similar to those of the healthy
      volunteers. In score 2, the waves recorded irregular rhythm and lower variables
      than the controls. Score 3 showed a "silent" EEG without waves. CONCLUSION: The
      electric activity in GERD exhibited 3 different patterns depending on the stages
      of GERD. Score 1 exhibited a normal EEG which apparently denotes normal
      esophageal motility. Score 2 recorded irregular electric waves variables which
      are presumably indicative of decreased esophageal motility and reflux clearance.
      In score 3, a "silent" EEG was recorded with probably no acid clearance. It is
      postulated that the interstitial cells of Cajal which are the electric activity
      generators, are involved in the inflammatory process of GERD. Destruction of
      these cells appears to occur in grades that are in accordance with GERD scores.
      The EEG seems to have the potential to act as an investigative tool in the
      diagnosis of GERD stages.

PMID- 15462681
TI  - Underweight is independently associated with mortality in post-operative and non
      operative patients admitted to the intensive care unit: a retrospective study.
AB  - BACKGROUND: Low and high body mass index (BMI) have been recently shown to be
      associated with increased and decreased mortality after ICU admission,
      respectively. The objective of this study was to determine the impact of BMI on
      mortality and length of stay in patients admitted to the intensive care unit
      (ICU). METHODS: In this retrospective cohort study, the Acute Physiology and
      Chronic Health Evaluation (APACHE) III database of patients admitted to the ICUs
      of a tertiary academic medical center, from January 1997 to September 2002, was
      crossed with a Hospital Rule-based Systems database to obtain the height and
      weight of the patients on admission to the ICU. The cohort was divided in post
      operative and non-operative groups. We created the following five subgroups based
      on the BMI: <18.5, 18.5 to 24.9, 25 to 29.9, 30.0 to 39.9, >/= 40.0 Kg/m2. A
      multiple logistic regression analysis was used to determine the independent
      impact of BMI on hospital mortality. The ICU length of stay ratio was defined as
      the ratio of the observed to the predicted LOS. P-value < 0.05 was considered
      significant. The 95% confidence interval (CI) was calculated for the odds ratio
      (OR). RESULTS: BMI was available in 19,669 of the 21,790 patients in the APACHE
      III database; 11,215 (57%) of the patients were admitted post-operatively. BMI <
      18.5 was associated with increased mortality in both post-operative (OR = 2.14,
      95% CI, 1.39 to 3.28) and non-operative (OR = 1.51, 95% CI, 1.13 to 2.01)
      patients. Post-operative patients with a BMI between 30.0 to 39.9 had a lower
      mortality rate (OR = 0.68, 95% CI, 0.49 to 0.94). Post-operative patients with
      BMI <18.5 or BMI >/= 40 had an ICU length of stay ratio significantly higher than
      patients with BMI between 18.5 to 24.9. The addition of BMI < 18.5 did not
      improve significantly the accuracy of our prognostic model in predicting hospital
      mortality. CONCLUSIONS: Low BMI is associated with higher mortality in both post-
      and non-operative patients admitted to the ICU. LOS is increased in post
      operative patients with low and high BMIs.

PMID- 15462682
TI  - Patients' perspectives on high-tech home care: a qualitative inquiry into the
      user-friendliness of four technologies.
AB  - BACKGROUND: The delivery of technology-enhanced home care is growing in most
      industrialized countries. The objective of our study was to document, from the
      patient's perspective, how the level of user-friendliness of medical technology
      influences its integration into the private and social lives of patients.
      Understanding what makes a technology user-friendly should help improve the
      design of home care services. METHODS: Four home care interventions that are
      frequently used and vary in their technical and clinical features were selected:
      Antibiotic intravenous therapy, parenteral nutrition, peritoneal dialysis and
      oxygen therapy. Our qualitative study relied on the triangulation of three
      sources of data: 1) interviews with patients (n = 16); 2) interviews with carers
      (n = 6); and 3) direct observation of nursing visits of a different set of
      patients (n = 16). Participants of varying socioeconomic status were recruited
      through primary care organizations and hospitals that deliver home care within
      100 km of Montreal, the largest urban area in the province of Quebec, Canada.
      RESULTS: The four interventions have both a negative and positive effect on
      patients' lives. These technologies were rarely perceived as user-friendly, and
      user-acceptance was closely linked to user-competence. Compared with acute I.V.
      patients, who tended to be passive, chronic patients seemed keener to master
      technical aspects. While some of the technical and human barriers were managed
      well in the home setting, engaging in the social world was more problematic. Most
      patients found it difficult to maintain a regular job because of the high
      frequency of treatment, while some carers found their autonomy and social lives
      restricted. Patients also tended to withdraw from social activities because of
      social stigmatization and technical barriers. CONCLUSIONS: While technology
      contributes to improving the patients' health, it also imposes significant
      constraints on their lives. Policies aimed at developing home care must clearly
      integrate principles and resources supporting the appropriate use of technology.
      Close monitoring of patients should be part of all technology-enhanced home care
      programs.

PMID- 15462683
TI  - Renal outcome in adults with renal insufficiency and irregular asymmetric
      kidneys.
AB  - BACKGROUND: The commonest cause of end-stage renal failure (ESRF) in children and
      young adults is congenital malformation of the kidney and urinary tract. In this
      retrospective review, we examine whether progression to ESRF can be predicted and
      whether treatment with angiotensin converting enzyme inhibitors (ACEI) can delay
      or prevent this. METHODS: We reviewed 78 patients with asymmetric irregular
      kidneys as a consequence of either primary vesico-ureteric reflux or renal
      dysplasia (Group 1, n = 44), or abnormal bladder function (Group 2, n = 34).
      Patients (median age 24 years) had an estimated GFR (eGFR) < 60 ml/min/1.73 m2
      with at least 5 years of follow up (median 143 months). 48 patients received
      ACEI. We explored potential prognostic factors that affect the time to ESRF using
      Cox-regression analyses. RESULTS: At start, mean (SE) creatinine was 189 (8)
      mumol/l, mean eGFR 41 (1) ml/min 1.73 m2, mean proteinuria 144 (14) mg/mmol
      creatinine (1.7 g/24 hrs). Of 78 patients, 36 (46%) developed ESRF, but none of
      19 with proteinuria less than 50 mg/mmol and only two of 18 patients with eGFR
      above 50 ml/min did so. Renal outcome between Groups 1 and 2 appeared similar
      with no evidence for a difference. A benefit in favour of treatment with ACEI was
      observed above an eGFR of 40 ml/min (p = 0.024). CONCLUSION: The similar outcome
      of the two groups supports the nephrological nature of progressive renal failure
      in young men born with abnormal bladders. There is a watershed GFR of 40-50
      ml/min at which ACEI treatment can be successful at improving renal outcome.

PMID- 15462684
TI  - Extreme conservation of noncoding DNA near HoxD complex of vertebrates.
AB  - BACKGROUND: Homeotic gene complexes determine the anterior-posterior body axis in
      animals. The expression pattern and function of hox genes along this axis is
      colinear with the order in which they are organized in the complex. This
      'chromosomal organization and functional correspondence' is conserved in all
      bilaterians investigated. Genomic sequences covering the HoxD complex from
      several vertebrate species are now available. This offers a comparative genomics
      approach to identify conserved regions linked to this complex. Although the
      molecular basis of 'colinearity' of Hox complexes is not yet understood, it is
      possible that there are control elements within or in the proximity of these
      complexes that establish and maintain the expression patterns of hox genes in a
      coordinated fashion. RESULTS: We have compared DNA sequence flanking the HoxD
      complex of several primate, rodent and fish species. This analysis revealed an
      unprecedented conservation of non-coding DNA sequences adjacent to the HoxD
      complex from fish to human. Stretches of hundreds of base pairs in a 7 kb region,
      upstream of HoxD complex, show 100% conservation across the vertebrate species.
      Using PCR primers from the human sequence, these conserved regions could be
      amplified from other vertebrate species, including other mammals, birds,
      reptiles, amphibians and fish. Our analysis of these sequences also indicates
      that starting from the conserved core regions, more sequences have been added on
      and maintained during evolution from fish to human. CONCLUSION: Such a high
      degree of conservation in the core regions of this 7 kb DNA, where no variation
      occurred during approximately 500 million years of evolution, suggests critical
      function for these sequences. We suggest that such sequences are likely to
      provide molecular handle to gain insight into the evolution and mechanism of
      regulation of associated gene complexes.

PMID- 15462685
TI  - Managing patients with recurrent acute exacerbations of chronic bronchitis: a
      common clinical problem.
AB  - Chronic obstructive pulmonary disease (COPD) affects 15 million people and is the
      fourth leading cause of death in the United States. It places a considerable
      burden on the healthcare system, with exacerbations contributing to a significant
      proportion of this burden. Patients with recurrent exacerbation, who experience
      more than 2 exacerbations per year, are especially difficult to manage. Several
      potential host, pathogen, and treatment factors can be identified that contribute
      to recurrent exacerbation. Patients with recurrent exacerbations are often
      exposed to frequent courses of antimicrobials. Therefore, antimicrobial
      resistance among common bacterial pathogens is likely to be prevalent in this
      group of patients, and further complicates therapy in this already difficult-to
      treat patient population. In the management of patients with recurrent
      exacerbation, one goal should be to decrease the frequency of exacerbations, for
      which several strategies are suggested. In this article, we will review available
      literature identified through an extensive search of Medline and PubMed on the
      characteristics and approach to management of these difficult-to-treat patients.
      There is a substantial need for more research to understand the etiology and
      identify efficacious interventions to reduce the frequency of exacerbations of
      COPD.

PMID- 15462686
TI  - A randomized controlled study comparing rofecoxib, diclofenac sodium, and placebo
      in post-bunionectomy pain.
AB  - OBJECTIVE: The relative efficacy of rofecoxib, diclofenac sodium, and placebo
      were compared in the treatment of acute pain after bunionectomy surgery. RESEARCH
      DESIGN AND METHODS: This was a double-blind, randomized, two-part study of 252
      patients with moderate-to-severe pain the day after first metatarsal
      bunionectomy. Patients were treated with a single dose of rofecoxib 50 mg (N =
      85), enteric-coated diclofenac sodium 100 mg (N = 85), or placebo (N = 82) on
      study Day 1 (Part I), and subsequently with daily rofecoxib 50 mg or placebo
      (diclofenac patients switched to placebo) over study Days 2-5 (Part II). Patients
      rated their pain at 16 time points over the first 24 h. Primary endpoint was
      total pain relief over 8 h (TOPAR8). Pre-specified secondary endpoints on Day 1
      included onset of analgesia, peak pain relief, and duration of response. For Part
      II, supplemental analgesia use with rofecoxib compared to placebo was pre
      specified for analysis over Days 2-5, with the focus on Days 2-3. Adverse
      experiences were recorded over Days 1-5. RESULTS: For TOPAR8 scores, rofecoxib 50
      mg was significantly more effective than placebo (9.5 vs. 3.7, p < 0.001) and
      diclofenac (9.5 vs. 5.0, p < 0.001). Onset of analgesia was more rapid with
      rofecoxib than placebo (p = 0.003) and diclofenac (p = 0.019); proportion of
      patients achieving onset within 4 h with rofecoxib, diclofenac, and placebo was
      46%, 27%, and 23%, respectively. Peak pain relief was greater with rofecoxib
      (1.8) than diclofenac (1.2, p = 0.004) and placebo (1.0, p < 0.001). Diclofenac
      and placebo patients required supplemental analgesia sooner than rofecoxib
      patients (2:03 h vs. 4:02 h, p < 0.001 and 1:41 h vs. 4:02 h, p < 0.001).
      Rofecoxib patients used significantly less (p < 0.001) supplemental analgesia
      than placebo patients over Days 2-3 (1.1 tablets/day vs. 2.1 tablets/day) and
      Days 2-5 (0.9 tablets/day vs. 1.8 tablets/day). No significant differences in
      adverse experiences between treatments were seen. CONCLUSION: Rofecoxib 50 mg was
      significantly more effective than placebo on all measures of treatment of post
      bunionectomy pain. Rofecoxib 50 mg was significantly more effective than
      diclofenac sodium 100 mg based on Day 1 endpoints of total pain relief, onset
      time, and duration of response. All study medications were generally well
      tolerated.

PMID- 15462687
TI  - The upper gastrointestinal safety of rofecoxib vs. NSAIDs: an updated combined
      analysis.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are nonspecific cyclo
      oxygenase (COX-1/COX-2) inhibitors and are associated with gastrointestinal (GI)
      toxicity attributable to COX-1 inhibition. Rofecoxib, a COX-2 specific inhibitor,
      was developed to provide similar efficacy and less GI toxicity than NSAIDs.
      OBJECTIVE: To update the results of a previously performed analysis of the
      incidence of upper GI perforations, symptomatic gastroduodenal ulcers, and upper
      GI bleeding (PUBs) with rofecoxib compared with non-selective NSAIDs. RESEARCH
      DESIGN AND METHODS: We compared the incidence of PUBs in a combined analysis of
      20 randomized, double-blind, clinical trials of rofecoxib versus NSAIDs. Men and
      women (N = 17,072) from multinational trial sites with osteoarthritis or
      rheumatoid arthritis were studied. There was no upper age limit in any of the
      trials. Investigator-reported PUBs were reviewed by a blinded, external
      adjudication committee using pre-specified criteria. The incidence of confirmed
      PUBs, the main outcome measure, among patients treated with rofecoxib 12.5 mg, 25
      mg, or 50 mg (combined, N = 10 026) was compared to that among patients treated
      with ibuprofen, diclofenac, nabumetone, or naproxen (combined, N = 7046).
      RESULTS: The incidence of PUBs over 24.8 months was significantly lower with
      rofecoxib vs. NSAIDs (cumulative incidence 1.6% vs. 3.1%, p < 0.001; rate/100
      patient-years 0.74 vs. 1.87; relative risk 0.36, 95% CI 0.24, 0.54). Results of
      subgroup analyses and comparisons of rofecoxib with individual NSAID comparators
      were consistent with the primary result, as was an analysis in patients with no
      PUB risk factors. DISCUSSION: The analysis demonstrated a consistently lower
      incidence of confirmed PUBs with rofecoxib than with NSAIDs over 24.8 months.
      These results confirm those of a previous smaller combined analysis of clinical
      trials with rofecoxib vs. non-selective NSAIDs in OA patients only, in which the
      risk reduction for confirmed PUBs was approximately 50%. In addition, this
      analysis demonstrated risk reductions with rofecoxib vs. NSAIDs in risk subgroups
      and in patients who did not have any known risk factors for PUBs consistent with
      the primary result. Some of the studies in this analysis required scheduled
      endoscopies. Asymptomatic upper GI ulcers or bleeding diagnosed during scheduled
      procedures were not included in the primary endpoint, which may have caused a
      bias against rofecoxib. CONCLUSIONS: Treatment with rofecoxib was associated with
      a statistically significantly (p < 0.001) lower incidence of PUBs than was
      treatment with NSAIDs. The difference was maintained in subgroups of patients
      with risk factors, as well as in those with no risk factors, for PUBs.

PMID- 15462688
TI  - The effect of montelukast on rhinitis symptoms in patients with asthma and
      seasonal allergic rhinitis.
AB  - OBJECTIVE: The objective of this study was to evaluate montelukast 10 mg daily as
      treatment for allergic rhinitis in patients with symptomatic allergic rhinitis
      and active asthma during the allergy season. METHODS: This was a multicenter
      study of 831 patients (ages 15 years-85 years) with seasonal allergen
      sensitivity, active symptoms of seasonal allergic rhinitis, and active asthma.
      Following a single-blind, placebo run-in period of 3 days-5 days, patients were
      randomized to oral montelukast 10 mg (n = 415) or placebo (n = 416) daily during
      the 2-week, double-blind, active-treatment period. MAIN OUTCOME MEASURES: The
      primary endpoint was Daily Rhinitis Symptoms score, average of Daytime Nasal
      Symptoms and Nighttime Symptoms, as self-rated by patients on a 0-3 scale on
      daily diaries. RESULTS: Montelukast reduced the Daily Rhinitis Symptoms score:
      difference between montelukast and placebo in mean change from baseline was -0.12
      [95% CI -0.18, -0.06; p < or = 0.001]. Similar improvements were seen in Daytime
      Nasal Symptoms (-0.14 [-0.21, -0.07; p < or = 0.001]) and Nighttime Symptoms (
      0.10 [-0.16, -0.04; p < or = 0.001]). Improvements (p < 0.05) were seen in
      Daytime Eye Symptoms and in the secondary endpoints of Global Evaluations of AR
      by Patient and by Physician, and Rhinoconjunctivitis Quality of Life. In
      exploratory analyses, improvement in rhinitis symptoms was numerically (though
      not statistically) larger in patients with greater levels of asthma at study
      start. Montelukast provided benefit in the Global Evaluations of Asthma by
      Patient and by Physician: mean differences were -0.24 [-0.41, -0.06; p = 0.008]
      and -0.17 [-0.33, -0.01; p = 0.037]. Similarly, as-needed beta-agonist use
      (puffs/day) was reduced with montelukast (p < or = 0.005). CONCLUSION:
      Montelukast provides significant relief from symptoms of seasonal allergic
      rhinitis, while also conferring a benefit for asthma, in patients with both
      allergic rhinitis and asthma.

PMID- 15462689
TI  - Provision of cardiovascular protection by ACE inhibitors: a review of recent
      trials.
AB  - This paper reports the rationale for the cardiovascular protective effects of ACE
      inhibitors (ACEI) and reviews the overall results of recent randomized clinical
      trials. ACEI improve the vasoconstrictive/vasodilatory balance by blocking the
      formation of angiotensin II and preventing the degradation of bradykinin. In
      vitro, animal and human experimental studies have shown that ACEI have several
      properties: They promote vasodilation, limit neurohormonal activation and
      vasoconstriction during ischemia, improve endothelial function by reducing
      oxidative stress, slow down the development of atherosclerosis; improve
      fibrinolytic balance, inhibit platelet activation and reverse negative vascular
      remodelling. Previous trials have shown that ACEI reduced cardiovascular events
      in patients with heart failure or ventricular dysfunction. These findings have
      recently been extended to trials using lipophilic ACEI with high affinity for
      tissue ACE i.e. those most likely to have high antiatherosclerotic efficacy. In
      PROGRESS (n = 6105), a perindopril-based regimen reduced recurrent stroke by 28%
      and substantially reduced cardiac outcomes among individuals with cerebrovascular
      disease. In HOPE (n = 9297), ramipril reduced the composite outcome
      (cardiovascular death, myocardial infarction and cerebrovascular accident) by 22%
      in patients with high cardiovascular risk. EUROPA (n = 12 218) showed that
      perindopril reduced cardiovascular mortality, myocardial infarction and cardiac
      arrest by 20% in coronary artery disease patients whatever their level of risk.
      The central role of long-acting lipophilic ACEI for cardiovascular protection has
      been clearly established and they should now be considered as a routine treatment
      for secondary prevention as aspirin, beta blockers and statins.

PMID- 15462690
TI  - Lipid-modifying effects of rosuvastatin in postmenopausal women with
      hypercholesterolemia who are receiving hormone replacement therapy.
AB  - OBJECTIVE: To evaluate the efficacy and safety of rosuvastatin in postmenopausal
      women with hypercholesterolemia who are receiving hormone replacement therapy
      (HRT) in a randomized, double-blind, placebo-controlled trial. METHODS: After a 6
      week dietary lead-in period, 135 postmenopausal women who had been taking a
      stable HRT regimen for at least 3 months were randomized to receive rosuvastatin
      5 mg, 10 mg or placebo for 12 weeks. Fasting levels of low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total
      cholesterol (TC), and triglycerides (TG) were assessed at weeks 0, 2, 6, 10, and
      12; apolipoprotein (Apo) B and Apo A-I were measured at weeks 0 and 12. RESULTS:
      Rosuvastatin 5 mg and 10 mg significantly reduced LDL-C by 38% (SE = 2.1) and 49%
      (SE = 2.1), respectively, compared with placebo (1% [SE = 2.1]; p < 0.001). TC,
      TG, Apo B, and all lipid ratios examined (LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C,
      and Apo B/Apo A-I) were also reduced significantly by both rosuvastatin doses (p
      < 0.001). HDL-C levels increased significantly in the rosuvastatin groups (11%
      and 8% for 5 mg and 10 mg, respectively, vs. -0.5% for placebo; p < 0.001), as
      did Apo A-I levels (p < 0.05). The combination of rosuvastatin plus HRT was well
      tolerated with no apparent differences among treatments in the numbers or types
      of adverse events reported. CONCLUSIONS: Rosuvastatin 5 mg or 10 mg once daily is
      a well-tolerated and highly efficacious lipid-lowering therapy in postmenopausal
      women receiving HRT.

PMID- 15462691
TI  - The place of inhaled corticosteroids in chronic obstructive pulmonary disease.
AB  - The role of systemic corticosteroids in the treatment of exacerbations of chronic
      obstructive pulmonary disease (COPD) is well established. However, despite being
      frequently prescribed for the treatment of COPD, the clinical utility of inhaled
      corticosteroids (ICS) is less clearly defined. This review article seeks to
      clarify the role of ICS in the clinical management of COPD through a review of
      key pivotal short-, medium- and long-term studies in this field. Studies for
      inclusion in this review were identified by means of a computerised search of
      several databases (including MEDLINE, BIOSIS and EMBASE) from 1980 to 2003. While
      individual clinical and epidemiological studies have yielded conflicting results,
      meta-analysis of available data suggests that ICS may reduce the frequency and
      severity of exacerbations, the number of hospitalisations and the mortality rate,
      as well as yielding improvements in lung function and health-related quality of
      life (HRQL) in some subgroups of COPD patients. More recently, clinical trials
      evaluating the effect of combination therapy with ICS and long-acting beta2
      agonists (LABA) have shown significant effects on the prevention of exacerbations
      and HRQL. Emerging data are expected to clarify the role of ICS in the management
      of patients with COPD of different severities as well as the place of treatment
      with ICS/LABA combinations in the management of this chronic and disabling
      disorder.

PMID- 15462692
TI  - The impact of migraine on work, family, and leisure among young women -- a
      multinational study.
AB  - OBJECTIVE: To assess the impact of migraine on work, family, and leisure among
      young women who were employed full or part time, or as a full-time student.
      RESEARCH DESIGN AND METHODS: This cross-sectional telephone survey with 6-month
      recall was conducted in Israel and eight European countries (Finland, Germany,
      Greece, Italy, Norway, Spain, Sweden, and The Netherlands). Random-digit dialing
      was used to identify study participants: women 18-35 years of age with migraine,
      who used medication to treat their migraine, and who were employed or full-time
      students. RESULTS: Of 1810 participants, 42% self-reported having a physician
      diagnosis of migraine. During the prior 6 months, 46% of participants missed at
      least 1 day of work or school and 74% were prevented from functioning fully at
      work or school because of migraine. Mean work/school absenteeism due to migraine
      was 1.9 days over 6 months (range, 0.8 days in Sweden to 2.8 days in Norway).
      Over half of participants reported one or more occurrences of being unable to
      spend time with family or friends (62%) or being unable to enjoy recreational or
      leisure activities (67%) because of migraine. The percentage of study
      participants using triptans was lowest in southern Europe and highest in the
      Nordic countries, ranging from 1% in Greece to 50% in Sweden. Country, age,
      marital status, physician diagnosis of migraine, and number of migraines or
      severe headaches in the prior year were independent predictors of the mean number
      of days of migraine-related work loss. Migraine-related work loss was lowest in
      Sweden and greatest in Greece, Israel, and The Netherlands. Higher work loss was
      recorded for those 18-24 years of age; those who were separated, widowed, or
      divorced; those with migraine diagnosed by a physician; and those with more
      frequent migraines or severe headaches (> or =24/year). The 6-month recall period
      used when estimating patient-reported work loss, and identifying participants
      with migraine based on self-reported migraine or severe headache, were the most
      important limitations of the study. CONCLUSIONS: We found substantial migraine
      related impairment of productivity at work and school as well as of family and
      leisure time among young women in Israel and eight European countries.

PMID- 15462694
TI  - Efficacy and tolerability of an ulcer compression stocking for therapy of chronic
      venous ulcer compared with a below-knee compression bandage: results from a
      prospective, randomized, multicentre trial.
AB  - OBJECTIVE: To investigate the possibility of improving healing rates in ulcus
      cruris venosum by using an ulcer compression stocking (U-Stocking) (Venotrain
      ulcertec) as compared to compression bandages. RESEARCH DESIGN AND SETTING:
      Prospective, multicentre, open-labelled, randomized, active-controlled study with
      blinded assessment of the primary endpoint. Sixteen phlebology outpatient clinics
      in Germany or the Netherlands or German medical practices specialized in
      phlebology. PATIENTS AND METHODS: 134 patients with venous leg ulcers entered the
      study. Among others, patients with infected ulcer or obesity were excluded. 121
      patients were eligible for primary efficacy analyses. U-Stocking or bandages
      applied for at least eight hours per day and for up to 12 weeks. The primary
      endpoint was the healing rate after 12 weeks as assessed by planimetric measures.
      The secondary outcome variables were time to healing, changes in ulcer size
      (planimetry), experience of use and patient compliance. MAIN OUTCOME MEASURES:
      Therapy with the U-Stocking produced a significantly higher rate of complete
      healing of 47.5% (29/61) versus 31.7% (19/60) with bandages, 1-sided p = 0.0129
      [CI: 95% for differences: 4.3% to 28.5%]. Mean time to healing was 46 days in
      both groups. Time required for application of the U-Stocking was a mean of 5.4
      min (SD 5.4) versus 8.5 min (SD 6.5) for bandages, p = 0.0001. Around three
      patients in each treatment group were affected by serious adverse events. All
      treatment-related adverse events are known for compression therapy. CONCLUSIONS:
      The U-Stocking was superior to bandages in compression therapy for venous ulcer.
      This is of significance to new treatment standards as well as to future studies
      of longer term therapy (> 12 weeks) for unhealed ulcers or prevention of
      recurrence.

PMID- 15462693
TI  - Long-term effects of rivastigmine treatment on neuropsychiatric and behavioral
      disturbances in nursing home residents with moderate to severe Alzheimer's
      disease: results of a 52-week open-label study.
AB  - OBJECTIVES: To evaluate the safety and efficacy of long-term treatment with
      rivastigmine (3-12 mg/day) and its effects on neuropsychiatric and behavioral
      disturbances in nursing home patients with moderate to severe probable
      Alzheimer's disease (AD). METHODS: A prospective, multicenter 26-week open-label
      extension to a 26-week open-label study (52 week results) of rivastigmine
      treatment in patients with Mini-Mental State Examination (MMSE) scores of 6-15
      inclusive, residing in nursing homes at 13 centers in the US. Effects of
      treatment with rivastigmine for up to 52 weeks on neuropsychiatric and behavioral
      symptoms were examined using the Neuropsychiatric Inventory-Nursing Home (NPI-NH)
      scale. Cognitive function was assessed by the MMSE, and the Naming Objects and
      Fingers Test (NOFT) subset of the Alzheimer's Disease Assessment Scale --
      Cognitive subscale (ADAS-Cog). Global functioning was assessed using the
      simplified Clinician's Interview-Based Impression of Change Plus Caregiver Input
      (CIBIC-Plus). RESULTS: Rivastigmine (3-12 mg/day) significantly improved
      neuropsychiatric and behavioral symptoms compared to baseline (in patients with
      specific behavioral disturbances at baseline) in observed cases (OC) and last
      observation carried forward (LOCF) analyses. Over 52 weeks, treatment with
      rivastigmine significantly improved 10 of 12 individual NPI-NH domains from
      baseline in LOCF patients with symptoms present at baseline. Cognitive function
      was stable, indicated by the lack of decline in MMSE and the NOFT. Global
      function was stabilized or improved in greater than half of the patients as
      indicated by the simplified CIBIC-Plus scores. CONCLUSION: Rivastigmine showed
      potential benefit in the long-term treatment of behavioral symptoms as well as
      cognitive and global functioning in nursing home residents with moderate to
      severe AD with concurrent behavioral symptoms present at baseline. Although these
      results suggest that treatment with rivastigmine may have beneficial behavioral
      effects and cognitive benefits on patients with moderate to severe AD, they are
      subject to the limitations of an open-label study.

PMID- 15462695
TI  - The effect of irbesartan in reducing cardiovascular risk in hypertensive type 2
      diabetic patients: an observational study in 16,600 patients in primary care.
AB  - OBJECTIVES: As arterial hypertension substantially increases the risk of
      premature death, cardiovascular disease and renal insufficiency in patients with
      type 2 diabetes, effective and safe antihypertensive therapy is of importance.
      Therefore, the effect of irbesartan as monotherapy, or in fixed combination with
      hydrochlorothiazide, on blood pressure, metabolic parameters and microalbuminuria
      and the safety and tolerability of the drug were assessed. RESEARCH DESIGN AND
      METHODS: Multicentric, prospective, open phase IV study over 3 months in 16,600
      patients with the clinical diagnoses of hypertension and type 2 diabetes. Blood
      pressure was measured sphygmometrically and albuminuria was assessed with semi
      quantitative urine dipsticks. MAIN OUTCOME MEASURES: Systolic (SBP) and diastolic
      (DBP) blood pressure reduction, proportion of patients with microalbuminuria and
      cardiovascular risk calculated based on the SCORE score, each after a follow-up
      of 3 months compared to baseline. Number and nature of adverse events (AEs).
      RESULTS: The sample consisted of 51.3% men, mean age was 62.2+/-10.7 years, 53.9%
      of patients were overweight and 26.4% were obese. Mean SBP/DBP decrease after 3
      months was 22.3/11.2 mmHg. The BP lowering effect was similar in the analyses of
      various subgroups (according to age group, sex, presence of micro- or
      macrovascular complications). Irbesartan treatment reduced the percentage of
      patients with microalbuminuria from 45.6% to 30.6% at 3 months (32.9% relative
      reduction). Metabolic parameters (lipids, blood glucose, HbA1c) and weight were
      improved significantly or showed trends for improvement, respectively. The mean
      10-year cardiovascular risk as calculated with the SCORE score was decreased from
      a baseline value of 9.8% to 5.7% (-58% relative reduction). Tolerability was
      excellent: only 0.3% experienced an AE. CONCLUSIONS: Treatment with irbesartan in
      patients with concomitant hypertension and type 2 diabetes led to large blood
      pressure reductions. In view of the renoprotective effect documented by the
      reduced rate of patients with albuminuria, and the improvement of further
      metabolic parameters, these changes translate into a reduction of cardiovascular
      risk.

PMID- 15462696
TI  - Healthcare costs and prescription adherence with introduction of
      thiazolidinedione therapy in Medicaid type 2 diabetic patients: a retrospective
      data analysis.
AB  - OBJECTIVES: Outcomes in patients with type 2 diabetes may vary depending on the
      antidiabetic medication used. Observational studies of outcomes of diabetes
      pharmacotherapy are needed to understand the implications of choice of controller
      in different populations. This study compared differences in total health care
      costs, medication adherence, and persistence in patients with type 2 diabetes
      enrolled in the North Carolina Medicaid Program that were newly started on
      thiazolidinedione (TZD) therapy with patients starting other oral antidiabetics
      during the same period. In addition differences among the TZDs with respect to
      these outcomes were examined. METHODS: A total of 1774 patients newly starting
      TZD therapy between July 2001 and June 2002 were compared to 1709 patients
      starting other oral antidiabetic medication (metformin or sulfonylureas) for
      health care costs and outcomes in the post-medication start year. In addition, a
      sub-group analysis of health care costs in patients starting either TZD
      (pioglitazone [n = 1086] versus rosiglitazone [N = 688]) was compared. All
      included patients had complete enrollment for the 24 months of follow-up.
      Multivariate techniques incorporating health care utilization in the year prior
      to start of new therapy were utilized to determine the cost impact of one therapy
      versus another. RESULTS: Results of multiple regression analyses suggest that
      patients starting TZD have better treatment adherence and persistence in the post
      medication start year compared to patients starting other oral antidiabetics (13%
      increase in Medication Possession Ratios, and 10% increase in therapy persistence
      index, both p < 0.001). In addition, patients starting TZDs had 16.1% lower total
      annual health care costs (p < 0.01) compared to patients starting other oral
      antidiabetics. There were no differences in adherence and cost outcomes between
      the 2 TZDs. CONCLUSIONS: Introduction of thiazolidinedione therapy in a Medicaid
      enrolled type 2 diabetic population was associated with significantly improved
      treatment adherence, persistence, and lower annual health care costs in the post
      start year compared to patients starting other oral antidiabetics.

PMID- 15462697
TI  - Rationale for a non-inferiority clinical trial design focused on subpopulations.
AB  - Although double-blind, placebo-controlled clinical trials are utilized
      extensively to characterize the efficacy and safety of new treatment options, the
      characteristics of the trial participants often do not reflect those of the wider
      patient population. In most cases, one or more patient subgroups (whether defined
      by race, ethnicity, co-morbidity, concomitant medication, age, or gender) will be
      under-represented. Understanding treatment responses in these subpopulations is a
      vital component of the overall therapeutic profile of a medication. Several
      different approaches to subgroup analyses within a single trial have been
      described. In addition, meta-analytic and data pooling approaches utilize results
      from multiple clinical trials of similar design to increase the number of
      patients within a targeted subgroup. If the results from exploratory analyses are
      suggestive of a clinically relevant difference in treatment response for a
      particular subgroup, then implementation of a prospectively designed clinical
      trial may be warranted. In this commentary, we discuss the design and results of
      various studies that include subgroup analyses. In addition, we describe a novel
      study design with a non-inferiority subpopulation analysis (NISA) that may
      provide new insights with respect to subgroup analyses. The NISA study design
      relies on characterization of the dominant group of patients recruited to date in
      placebo-controlled trials. In the NISA study, the group of patients with those
      same characteristics is referred to as the Core group. The other key features of
      the NISA design include non-inferiority analyses comparing subgroups to the Core
      group and study conditions closely aligned with routine clinical practice
      (heterogeneous study population and open-label drug administration without
      placebo). Limitations of the NISA design include the requirement of previously
      conducted placebo-controlled trials, the inability to compare treatment response
      to placebo, and that NISA has yet to be validated in practice. We also describe
      the implementation of the NISA study design in two ongoing clinical trials. After
      completion of these two studies, the practical value of the NISA design can be
      more thoroughly evaluated.

PMID- 15462698
TI  - Comment on Hyperprolactinaemia and antipsychotic therapy in schizophrenia.

PMID- 15462699
TI  - Montelukast in asthmatic patients 6 years-14 years old with an FEV1 > 75%.
AB  - OBJECTIVES: Montelukast is a potent leukotriene receptor antagonist effective for
      treating asthma symptoms in adult and pediatric patients. The purpose of this
      analysis was to assess the clinical efficacy of montelukast, a potent leukotriene
      receptor antagonist, in a subgroup analysis of patients aged 6 years-14 years
      with milder asthma, defined as a percentage predicted forced expiratory volume in
      1 s (FEV1) > 75% using data from a clinical trial of pediatric patients with a
      broad range of asthma severities. RESEARCH DESIGN AND METHODS: The original
      previously published clinical trial was an 8-week multi-center, randomized,
      double-blind, parallel-group study conducted in 47 centers in the United States
      and Canada. The study compared the efficacy of once daily montelukast 5 mg to
      placebo in patients 6 years-14 years old with persistent asthma and an FEV1
      ranging from 50% to 85% of predicted. A total of 87 patients in the montelukast
      group and 51 patients in the placebo group were selected from the original cohort
      of 336 patients based on percentage predicted FEV1 of > 75%. The primary endpoint
      was percentage change in FEV1 from baseline compared with placebo over 8 weeks of
      active treatment. RESULTS: Montelukast significantly improved the primary
      endpoint of percentage change in FEV1 compared with placebo (p = 0.005). Other
      efficacy endpoints were significantly improved on montelukast similar to efficacy
      in the original study. CONCLUSION: Montelukast significantly improved FEV1,
      clinic measured peak expiratory flow (PEF), reduced nocturnal awakenings, and
      improved quality of life in children with milder persistent asthma defined as an
      FEV1 > 75% of predicted.

PMID- 15462700
TI  - The role of cilostazol in the treatment of intermittent claudication.
AB  - This paper represents a review, by experts, of current opinion and information on
      intermittent claudication (IC) and the role that cilostazol plays in its
      treatment. IC is a common and debilitating condition that has a significant
      adverse impact on health-related quality of life (HR-QoL). It is currently under
      recognised as a powerful marker of increased cardiovascular (CV) risk. The
      clinical priority is secondary prevention -- sometimes referred to as best
      medical therapy aimed at reducing CV risk. However, the priority for most
      patients (often overlooked by clinicians) is symptom relief: an increase in
      walking distance leading to an improvement in HR-QoL. The symptoms of IC may be
      improved by exercise, pharmacotherapy, and when these are unsuitable or
      unsuccessful, endovascular or surgical intervention. Cilostazol is indicated for
      the improvement of maximal and pain-free walking distance in patients with IC who
      do not have rest pain or tissue necrosis. In clinical trials, cilostazol improved
      symptoms both objectively and subjectively, and also improved HR-QoL. Cilostazol
      is usually well tolerated, with adverse events being generally mild to moderate
      in intensity, and transient or resolved after symptomatic treatment (e.g. non
      prescription analgesics). Such events only infrequently require permanent drug
      withdrawal. There are no interactions with other drugs commonly prescribed in
      patients with IC, such as statins and anti-platelet agents. Cilostazol also has a
      range of potentially beneficial effects that may in the future be proven to
      decrease CV risk and modify the underlying process of atherosclerosis. Cilostazol
      represents the best evidence-based pharmacological therapy available for the
      symptoms of IC and should be the first-line treatment for symptom improvement in
      appropriate patients. Based on the available treatment strategies, the paper
      presents a suggested algorithm for the management of IC highlighting the role of
      cilostazol.

PMID- 15462701
TI  - An economic evaluation of adjustable and fixed dosing with budesonide/formoterol
      via a single inhaler in asthma patients: the ASSURE study.
AB  - BACKGROUND: The severity of asthma varies between individuals and over time. As a
      result individuals may have marked variation in their need for asthma treatment.
      Adjustable dosing enables patients to assume greater involvement in managing
      their own condition. OBJECTIVE: To compare the costs and effectiveness of fixed
      dosing of budesonide/formoterol (Symbicort Turbohaler) with adjustable
      maintenance dosing. METHODS: A cost-effectiveness analysis was conducted from the
      perspective of the UK NHS. Adults with established asthma currently maintained on
      > or =400 microg per day inhaled corticosteroid were enrolled in 365 primary care
      centres in the UK. Patients were run-in on 2 inhalations twice daily of
      budesonide/formoterol 80/4.5 microg or budesonide/formoterol 160/4.5 microg
      (depending on steroid requirement) for 4 weeks and were then randomised to the
      Symbicort adjustable maintenance dosing plan (SAMD) (n = 782;
      budesonide/formoterol 1-4 inhalations twice daily depending on symptoms) or
      Symbicort fixed dosing (n = 771; 2 inhalations twice daily) for a further 12
      weeks. The primary effectiveness variable was clinically meaningful change in
      quality of life (QoL) assessed by the miniasthma quality of life questionnaire
      (AQLQ). Secondary effectiveness measures included symptom-free days with no short
      acting beta-agonist use. We assessed the costs of study medication, asthma
      related concomitant medication, primary care and hospital contacts. Confidence
      intervals were generated by nonparametric boot-strapping. RESULTS: Clinically
      meaningful improvement in QoL during the first 4 weeks was reported by 40.8% of
      enrolled patients. During the following 12 weeks, a net 1% (95% CI: -4%, 6%) of
      SAMD patients and 6% (95% CI: 1%, 10%) of fixed dosing patients reported further
      improvement. Effectiveness parameters did not differ significantly between groups
      during the study period. Mean daily cost per patient was pound sterling 1.13 (95%
      CI: pound sterling 1.08, pound sterling 1.18) in the SAMD group and pound
      sterling 1.31 (95% CI: pound sterling 1.27, pound sterling 1.34) in the fixed
      dosing. The difference in mean daily cost resulted in an annual per patient cost
      difference of pound sterling 65.70. Adjustable maintenance dosing with
      budesonide/formoterol provided equivalent QoL to fixed dosing at significantly
      lower cost.

PMID- 15462702
TI  - Risk factors for osteoporosis in postmenopausal African-American women.
AB  - BACKGROUND: Although postmenopausal African-American women are at lower risk for
      osteoporosis-related fractures compared with white women, fractures in African
      American women are associated with significantly higher morbidity and mortality.
      Therefore, early diagnosis and treatment of osteoporosis in this population is
      just as important as it is for other ethnic groups and worthy of the attention of
      physicians and healthcare organizations. OBJECTIVE: The purpose of this study was
      to evaluate risk factors for osteoporosis in postmenopausal African-American
      women. DESIGN: This was a retrospective, case-control study in 201 postmenopausal
      African-American women at a community-based osteoporosis center. Spine and hip
      bone mineral density measurements were obtained by dual-energy x-ray
      absorptiometry. Patient and family medical history, past and present
      pharmaceutical use, and dietary and exercise habits were collected using a
      patient self-administered questionnaire. RESULTS: Using the manufacturer's
      African-American referent database, 56 women had osteoporosis, 99 had osteopenia,
      and 46 had normal bone mineral density. Risk factors more common in the
      osteoporotic group compared with the normal group included sedentary lifestyle (P
      < 0.03), family history of osteoporosis (P < 0.03), low body mass index (P <
      0.05), and history of bilateral oophorectomy (P < 0.03). Polyarthritis was more
      prevalent in the normal versus the osteoporotic group (P < 0.001). In addition,
      premenopausal use of oral contraceptives (P < 0.005) and postmenopausal use of
      estrogen therapy (P < 0.05) were more common in the normal compared with the
      osteoporotic group. CONCLUSIONS: Many risk factors for osteoporosis in African
      American women are similar to those in white women and can aid in the selection
      of patients in need of bone density testing.

PMID- 15462703
TI  - The fungal phenomenon.

PMID- 15462707
TI  - Pediatric asthma: a look at adherence from the patient and family perspective.
AB  - Although extensive research has been done in an effort to understand and promote
      adherence in pediatric asthma, little progress has been made in reducing the
      prevalence of nonadherence. Some researchers argue that a paradigm shift is
      necessary to advance the adherence field. Despite the recent trend for increasing
      the role of families in determining treatment plans, a patient-centered approach
      has been lacking in adherence to a daily regimen. It is clear that, although
      patients and families show evidence of inadvertent nonadherence (eg,
      forgetfulness), they also engage in volitional or intentional nonadherence, via
      reasoned and purposeful decisions. Patients conduct "experiments" with their
      regimen components in an effort to balance the burden of disease with the burden
      of treatment. These experiments typically involve some degree of nonadherence.
      Perhaps, if researchers strive to better understand the decision-making process
      involved in these experiments, health care providers can guide families in making
      adherence decisions that would lead to attainment of treatment goals, improvement
      in quality of life, and realization of positive clinical outcomes.

PMID- 15462708
TI  - Risk factors for food allergy.
AB  - Food allergy is a common problem that often affects young children. Numerous
      factors affect the development of food allergy both prenatally and postnatally.
      These factors are genetic and environmental. Although little can be done post
      conception to alter a child's genetic risk for developing food allergy, early
      identification may permit alterations of the environment in which food allergy
      develops. Environmental factors operate both prenatally and postnatally. By
      understanding how these factors affect development of food allergy, it may be
      possible for parents to modulate the development of this difficult problem in
      their children.

PMID- 15462709
TI  - Evidence-based strategies for treatment of allergic rhinitis.
AB  - In this review, an evidence-based medicine approach to diagnosis and treatment
      for allergic rhinitis is reviewed. We performed a search of the medical
      literature for randomized, placebo-controlled trials of nonsedating
      antihistamines, intranasal corticosteroids, montelukast, azelastine, allergen
      immunotherapy, and anti-IgE. The mean numbers needed to treat were: nonsedating
      antihistamines--15.2; nasal corticosteroids--4.4; montelukast--14.3; azelastine-
      5.0; allergen immunotherapy--4.6; and anti-IgE--12.4. Treatment thresholds for
      use were: antihistamines--23%; nasal corticosteroids--8%; azelastine--16%;
      montelukast--8%; anti-IgE--50%; and immunotherapy--25%. When used appropriately,
      this information could become very useful for clinicians, particularly if cost,
      convenience, and other indirect factors can be included.

PMID- 15462710
TI  - Update on side effects from common vaccines.
AB  - Vaccines have had a tremendous impact on public health by reducing morbidity and
      mortality from a variety of virulent pathogens. However, unintended side effects
      continue to pose a potential risk that may outweigh the vaccine's protective
      attributes. In this review, we discuss recent articles and controversies
      pertaining to vaccine-associated adverse events. Included in the discussion are
      influenza, hepatitis B, measles-mumps-rubella, diphtheria-tetanus-pertussis,
      polio, Haemophilus influenzae type b, and rotavirus vaccines. The importance and
      contribution of vaccine constituents (such as thimerosal) to side effects is also
      reviewed.

PMID- 15462711
TI  - Exhaled nitric oxide in the clinical management of asthma.
AB  - Management of asthma has gradually evolved from the concept of controlling
      bronchial hyperresponsiveness to focusing on control of inflammation. The
      awareness of airway remodeling, and the emergence of data suggesting
      irreversibility of some of these changes, despite standard-of-care
      pharmacotherapies such as inhaled steroids, has highlighted the need for early
      detection; effective diagnosis and treatment; monitoring responses and adhering
      to treatment; and predicting exacerbations. Pre-clinical intervention strategies
      targeted toward picking up early suggestions of asthma before irreversible airway
      changes occur may open the door to primary prevention approaches. Although
      invasive methods, such as bronchial biopsy, remain the gold standard to
      understanding and treating asthma, there is a preference for noninvasive
      techniques for reasons of convenience, ease of use, and patient comfort. In this
      article, recent data that support the use of exhaled nitric oxide as a
      noninvasive biomarker of inflammation in clinical practice are reviewed.

PMID- 15462714
TI  - Treatment options for acute sinusitis in children.
AB  - Much controversy exists regarding the best diagnostic method for acute sinusitis,
      the efficacy of antibiotics, the best choice of antibiotics, the most appropriate
      duration of therapy, and the efficacy of ancillary measures and nasal
      corticosteroids. The therapeutic goal is to identify those children who are more
      likely to have bacterial sinusitis and unlikely to resolve spontaneously, who may
      require treatment with antibiotics. The inaccuracy of clinical signs and symptoms
      complicates further the management of these children. Acute sinusitis is expected
      to resolve spontaneously in most cases, including many cases of bacterial
      sinusitis. Antibiotics are needed only for a minority of non-self-resolving
      infections. Based on current resistance considerations, approximately 80% of
      bacterial infections are expected to respond to standard doses of amoxicillin.
      High-dose amoxicillin, amoxicillin/clavulanate, or other b-lactam antibiotics
      should be considered for children at high risk for carrying resistant organisms.
      Evidence for the effectiveness of ancillary measures is limited.

PMID- 15462713
TI  - Allergic fungal rhinosinusitis.
AB  - The combination of nasal polyposis, crust formation, and sinus cultures yielding
      Aspergillus was first noted in 1976 by Safirstein, who observed the clinical
      similarity that this constellation of findings shared with allergic
      bronchopulmonary aspergillosis (ABPA). Eventually, this disease came to be known
      as allergic fungal rhinosinusitis (AFRS). As clinical evidence of AFRS
      accumulated, controversy regarding its etiology, pathogenesis, natural history,
      and appropriate treatment naturally emerged. Despite past and current efforts,
      many of these controversies remain incompletely resolved, but continuing clinical
      study has illuminated some aspects of the disease and has led to an improved
      understanding of AFRS and its treatment. In this article, we review current data
      and theories regarding the pathophysiology and clinical presentation of AFRS, as
      well as the roles of various surgical and nonsurgical forms of therapy.

PMID- 15462715
TI  - Pharmacologic management of chronic rhinosinusitis, alone or with nasal
      polyposis.
AB  - Patients with chronic rhinosinusitis (CRS) and chronic rhinosinusitis with nasal
      polyposis (CRSwNP) commonly present with nasal obstruction, nasal discharge,
      facial pressure/pain, and hyposmia of prolonged duration. Recent evidence
      suggests that, despite clinical similarities, CRS and CRSwNP are distinct
      entities with separate inflammatory pathways and cytokine profiles. Antibiotics
      and nasal steroids are the mainstay of treatment in CRS, whereas combination
      systemic and nasal steroids are the foundation of CRSwNP management. Allergy
      therapy may play a significant role in CRS, whereas antileukotriene therapy has
      demonstrated promise in CRSwNP. Although prolonged medical therapy is usually
      necessary with both disorders, surgery may also be required to relieve refractory
      symptoms, and to improve sinus aeration and nasal access for topical therapy.

PMID- 15462716
TI  - Surgical management of chronic rhinosinusitis and nasal polyposis: a review of
      the evidence.
AB  - Functional endoscopic sinus surgery is a common adjunct to medical therapy in the
      management of chronic rhinosinusitis and nasal polyposis. As with most surgical
      procedures, there is a paucity of randomized, controlled clinical trials
      examining the use of functional endoscopic sinus surgery in the management of
      chronic rhinosinusitis and nasal polyposis. This is primarily a result of the
      physical and ethical conundrums faced in performing a study that involves
      comparing a surgical procedure with a placebo. However, there is documentation of
      the marked impact that chronic rhinosinusitis can have on the overall quality of
      life and evidence that this improves following combined surgical and medical
      intervention. There are many case series with large patient populations that have
      shown significant improvement in short- and long-term patient symptoms following
      surgery. These outcomes are expected to improve with even greater refinement of
      technology, experience, and instrumentation, and the quality of future studies
      may be improved by determining and using objective measures of success and,
      possibly, by the use of control groups.

PMID- 15462719
TI  - Hyperreactive malarious splenomegaly (tropical splenomegaly syndrome).
AB  - Hyperreactive malarious splenomegaly (HMS), formerly known as tropical
      splenomegaly syndrome (TSS), was recognized some 20 years ago as an entity
      distinct from the splenic enlargement resulting directly from malarial
      parasitaemia. Its basis appears to be a disturbance in the T-lymphocyte control
      of the humoral response to recurrent malaria, possibly linked to particular HLA
      Class II antigens. Gross overproduction of IgM antibodies leads to the formation
      of high molecular weight immune complexes, persistent gross splenomegaly
      recurrent episodes of profound anaemia and increased susceptibility to
      infections. Those with gross disease experience a high mortality, which
      constitutes a major public health problem in communities where the syndrome
      affects a majority of adults.

PMID- 15462718
TI  - Animal models of sinusitis: relevance to human disease.
AB  - Experimental animal models are necessary to assess the efficacy of both medical
      and surgical procedures. The researcher who wishes to confirm and publish his
      results must overcome controversies concerning the validity of his model and,
      therefore, needs guidelines for standardization. Various models are offered in
      the literature. In this article, the rabbit and murine models of experimental
      sinusitis and their relevance to human disease with anatomical, histopathologic,
      and microbiologic aspects are discussed.

PMID- 15462717
TI  - Health-related quality of life in patients with sinusitis.
AB  - The goal of treatment for patients with sinusitis is the prompt and complete
      relief of symptoms and consequent improvement in health-related quality of life
      (HRQL). HRQL has been defined as the component of overall quality of life,
      determined primarily by the person's health, which can be influenced by clinical
      interventions. HRQL is especially useful for conditions like sinusitis in which
      there is no gold-standard diagnostic test, and "objective" tests correlate poorly
      with disease severity and outcomes. Patients with sinusitis have measurable,
      significant decrements in HRQL. Many studies evaluating treatment efficacy in
      patients with sinusitis have used unvalidated HRQL measures, making their
      findings, at best, difficult to interpret or, at worst, potentially biased. In
      this article, we review the definition of HRQL, the meaning and importance of
      validating HRQL measures, the impact of sinusitis on HRQL, and validated measures
      of HRQL for use in research and in clinical practice.

PMID- 15462720
TI  - The reproductive biology of schistosomes.

PMID- 15462721
TI  - Selective expression of surface antigen genes in African trypanosomes.

PMID- 15462722
TI  - Insecticide resistance in the onchocerciasis control programme.

PMID- 15462723
TI  - Environmental monitoring of rivers in the onchocerciasis control programme.

PMID- 15462725
TI  - Autoimmunity in Chagas disease: the debate goes on.

PMID- 15462726
TI  - Eosinophilia in Isospora infections.

PMID- 15462727
TI  - Amblyomma variegatum and acute bovine dermatophilosus.

PMID- 15462728
TI  - Marginal notes on hormones.

PMID- 15462729
TI  - New approaches to schistosome identification.

PMID- 15462730
TI  - Insecticidal ear tags control cattle ectoparasites.

PMID- 15462731
TI  - Pathology in tropical medicine.
AB  - The pathology o f a parasitic disease is a major link between the investigating
      parasitologist and those concerned with its epidemiology, socioeconomic impact,
      clinical treatment and control. The epidemiologist requires information about the
      incidence and prevalence of major pathological lesions attributable to on
      infection, which in turn will determine the social and economic impact of the
      disease and thus its priority for control. For both diagnosis and treatment, the
      clinician requires an understanding of the pathological mechanisms, and the
      potential for new drugs or vaccine development largely depends on such
      understanding. Recent years have seen remarkable improvements in determining the
      nature of pathology associated with parasitic infections. and in understanding
      their causative mechanisms. With this issue, Parasitology Today begins a series
      of special reviews designed to bring together these insights into parasite
      pathology (see pages 271-282). In this introductory overview. Charles Mackenzie
      traces the origins and development of the science.

PMID- 15462732
TI  - Cell-mediated immunity in experimental cutaneous Leishmaniasis.
AB  - Forms of cutaneous leishmaniasis are caused by Leishmania major, L. tropica, L.
      mexicana, L. amazonensis and L. panamensis. Like all leishmanial species, these
      are obligate intracellular parasites of the mononuclear phagocyte system, with a
      restricted range of vertebrate hosts including humans, dogs, rodents and arboreal
      animals. The disease evolves chronically, usually with slow healing, but can
      sometimes become nonhealing, diffuse disseminating or relapsing. The parasite
      exists within the macrophages of the vertebrate host in the amastigote form.
      These transform into extracellular flagellated promastigotes in the gut of the
      sandfly vectors. The promastigotes can then be injected into new vertebrate hosts
      as the insects feed. Promastigotes, and to a lesser extent amastigotes, can now
      be grown in tissue culture. This, together with the use of inbred mouse strains
      that are susceptible to most of the Leishmania species which are pathogenic for
      man, has facilitated great advances in our understanding of the immunological
      control of leishmaniasis. However, as Eddy Liew points out, there are still many
      unanswered questions.

PMID- 15462733
TI  - The pathophysiology of severe falciparum malaria.
AB  - By the end of the 1940s, the clinical and pathological features of severe
      falciparum malaria had been well described by military physicians and
      pathologists working in theatres of war where the disease was endemic. From that
      time serious efforts were made to discover the pathophysiology of the severe
      manifestations of malaria because an understanding of these mechanisms forms an
      important basis for the clinical management of affected patients. Recently, after
      a period of neglect, there has been a revival of interest in malaria as a subject
      for clinical and laboratory research. In this article, Rodney Phillips and David
      Warrell review aspects of that work and attempt to unravel the mysteries of the
      pathophysiology of severe malaria in man.

PMID- 15462734
TI  - Host specificity of avian coccidia.

PMID- 15462735
TI  - Periodic reproduction of Onchocerca volvulus.

PMID- 15462737
TI  - Trends in Louse-Borne typhus.

PMID- 15462736
TI  - Echinococcus multilocularis not yet in Australia.

PMID- 15462738
TI  - Cyclosporin A: immune suppressant and antiparasitic agent.

PMID- 15462739
TI  - Vector control by electrodynamic spraying.

PMID- 15462741
TI  - Trichinosis outbreaks associated with horsemeat.

PMID- 15462740
TI  - No evidence for arthropod transmission of AIDS.

PMID- 15462742
TI  - Immunopathology of granuloma formation and fibrosis in schistosomiasis.
AB  - In schistosomiasis the deposition of parasite ova within host tissues is the
      initial event in a complex pathophysiological cascade which is characterized by
      granuloma formation, and may terminate in fibrosis and related sequelae (Fig. 1).
      In spite of intensive study, the complex relationship between infection and
      morbidity remains poorly understood. In this article, Michael Phillips and
      Patrick Lammie review current concepts of the mechanisms of granuloma formation
      and its regulation in schistosome infections.

PMID- 15462743
TI  - History, biology and control of sheep scab.
AB  - Sheep scab is one of the oldest known diseases of sheep. It is caused by either
      of the mange mites Psoroptes ovis (Fig. 1 and cover) or Sarcoptes scabiei. P.
      ovis causes irritation so intense that sheep become preoccupied with scratching,
      cease to feed and rapidly become emaciated. It should be eradicated on welfare
      grounds alone (Fig. 2).

PMID- 15462744
TI  - The chromosomes of Onchocerca volvulus.

PMID- 15462745
TI  - L-Glutamine influx in malaria-infected erythrocytes: a target for antimalarials?
AB  - When malaria parasites enter red blood cells they precipitate on influx of
      substrates necessary for their development. For example, intraerythrocytic
      trophozoites of Plasmodium falciparum use exogenous t-glutamine in increasing
      amounts during maturation from the ring-stage. This is made possible by a marked
      and selective increase in the permeability of the host cell membrane. Several
      compounds have now been identified as inhibitors of the l-glutamine influx
      induced by P. falciparum; they are all natural products - either analogues of l
      glutamine, or related to indigenous traditional remedies for malaria. In this
      article, Barry El ford shows that although these compounds may not be of
      immediate practical value as antimolarials, they can provide valuable insight
      into the mechanisms underlying the regulation of these parasite-mediated
      transport processes.

PMID- 15462746
TI  - Chronic infection as a major force in the evolution of the suppressor T-cell
      system.

PMID- 15462747
TI  - Hapantotypes: a possible solution to some problems of parasite nomenclature.
AB  - Parasites usually have several morphologically distinct stages in their life
      cycles. Some infect different host species at different stages of their
      development, and many are distinguished partly by the lesions caused in their
      hosts. Molecular techniques, seeking to clarify host-parasite relationships,
      often attempt definition o f species or subspecies in terms of enzyme profiles,
      DNA 'finger-prints', or other subcellulor characteristics. So, under the
      International Code of Zoological Nomenclature, what carries the species name?
      Which 'specimen' represents the unique name-bearing reference for a specific
      name? The problem is particularly daunting for parasitologists. In this article,
      Ray Williams discusses the idea that instead of a single 'type specimen', a suite
      of specimens - the hapontotype - representing several stages in the life cycle of
      a species would be a more useful concept.

PMID- 15462748
TI  - Fact and fiction in mosquito attraction and repulsion.

PMID- 15462749
TI  - Fluorescence recovery after photobleaching: applications to parasite surface
      membranes.

PMID- 15462750
TI  - Health of the urban poor in developing countries.
AB  - The urban poor are at the interface between underdevelopment and
      industrialization and their disease patterns reflect the problems of both. From
      the first they carry a heavy burden of infectious diseases and malnutrition,
      while from the second they suffer the typical spectrum of chronic and social
      diseases.

PMID- 15462752
TI  - The case for 'plant medicines'.

PMID- 15462751
TI  - WHO programme in environmental health in rural and urban development and housing.

PMID- 15462753
TI  - The mode of action of chloroquine and related malarial schizontocides.
AB  - Use of fast-acting blood schizontocidal drugs such as chloroqune, amodiaquine,
      mepacrine or quinine, is essential for the treatment of acute malaria infections.
      The spread of resistance in Plasmodium falciparum to chloroquine, the most useful
      of these drugs, has been a serious problem since the 1960s, and the resistant
      strains show various degrees of cross-resistance to other drugs. Design of
      replacement drugs requires knowledge of their modes of action and mechanisms of
      resistance. At present, there are two theories to explain the mode of action of
      chloroquine (Box 1). In this debate, Coy Fitch advances the hypothesis that
      chloroquine acts by delaying the sequestration of Ferriprotoporphyrin IX (FP)
      into malaria pigment, thereby allowing FP to exert its intrinsic cellular
      toxicity. In contrast, David Warhurst proposes a new 'Permease theory' suggesting
      that chloroquine is imported into the parasite cytoplasm on a membrane carrier
      (the permease) under the influence of a proton gradient; the drug would then
      interfere with lysosomal digestion of haemoglobin, thus starving the parasite of
      amino acids for protein synthesis.

PMID- 15462754
TI  - Antimalarial schizontocides: ferriprotoporphyrin IX interaction hypothesis.

PMID- 15462755
TI  - Antimalarial schizontocides: why a permease is necessary.

PMID- 15462756
TI  - Epidemiology of reindeer parasites.
AB  - Every Christmas we sing about Rudolph the red-nosed Reindeer, but do we give much
      thought to why his nose is red? The general consensus is that Rudolf has caught a
      cold, but as far as I know no proper diagnosis has been made of his abnormal
      condition. I think that, rather than having a cold, Rudolf is suffering from a
      parasitic infection of his respiratory system. To some this may seem a bit far
      fetched as one would not expect an animal living with Santa Claus at the North
      Pole to be plagued by parasites, but I shall show otherwise.

PMID- 15462757
TI  - The Organization of schistosomiasis control programmes.
AB  - A major constraint to the control of communicable diseases in developing
      countries is the lack of adequate institutionalization of public health
      activities. The usual political perception is that the public will benefit more
      from economic and social development than from public health interventions.
      Planners and politicians generally hold that investment in rural electrification,
      roads and education will bring more long-term benefit than equivalent investments
      in public health. Sadly therefore, public health interventions have usually been
      designed and implemented as short-term, high-return activities in an atmosphere
      of unrealistic optimism. This criticism can be applied to most tropical diseases,
      but the potential of new weapons against many of the most widespread parasitic
      diseases places some urgency on an analysis of the most effective way to
      implement these interventions. In an attempt to identify and begin to resolve
      some of these issues, The World Bank, WHO and McConnell Clark Foundation
      sponsored a workshop on the Organization and Management of Schistosomiasis and
      other Tropical Disease Control Programmes. The meeting addressed general issues
      of the organization of public health services, but focused on schistosomiasis
      where the development of effective, single oral dose chemotherapy (using
      oxamniquine or praziquantel) is seen as a realistic intervention for large-scale
      control throughout the 74 endemic countries. In this article, Bernhard Liese
      reviews the institutional questions, drawing examples from the often cited
      control programmes in Brazil, Ghana, Egypt, Morocco, Sudan and the Philippines.

PMID- 15462758
TI  - The physiology of itch.
AB  - The perception of itch is associated with many parasites and their vectors,
      especially following penetration of the skin by the parasites themselves, as in
      cercarial dermatitis of schistosome infections, or penetration of arthropod
      mouthparts during blood feeding. Many ectoparasites such as scabies, lice and
      fleas, provoke sensations of itch - even when the insects are no longer (or have
      never been) present, giving rise to the phenomenon of delusory parasitosis. Itch,
      and the host 'grooming' responses with which it is associated, is increasingly
      recognized as an important factor in modulating vector feeding behaviour, which
      can have profound effects on the transmission dynamics of vector borne parasites.
      As a background to future reviews of this developing subject, we asked John
      Alexander, author of the classic Arthropods and Human Skin (Springer-Verlag,
      1984), to explain what is itch, and to discuss what is known about its underlying
      Physiology.

PMID- 15462760
TI  - Traditional antiparasitic drugs in China.

PMID- 15462759
TI  - The potential of antispermatogenic drugs against trypanosomatids.
AB  - In recent years, two antispermatogenic drugs - gossypol and lonidamine (Fig. I) -
      have been reported to inhibit the growth of Trypanosoma cruzi in culture. In this
      article, Julio Turrens discusses the biochemical similarities between
      trypanosomatids and spermatozoa. and the potential o f these antispermatogenic
      drugs against the parasites.

PMID- 15462762
TI  - Phytoalexins: antiparasitics of higher plants.

PMID- 15462761
TI  - Novel antimalarial drugs from plants?
AB  - In all countries where malaria is endemic, plants are used in traditional
      medicine for treatment of the disease. Examples are numerous - the plant product
      data base napralert (Box I) lists 152 genera which are allegedly used for the
      treatment of malaria. But with the urgent need to develop new, safe and effective
      drugs against malaria, it is vital that such claims be fully investigated. In
      this article, David Phillipson and Melanie O'Neill discuss the potential of plant
      products for new antimoloriols, drawing attention particularly to the quassinoids
      - a diverse group of terpenoids from the family Simoroubaceoe.

PMID- 15462763
TI  - Traditional healers in Swaziland.

PMID- 15462764
TI  - Future policy of the Wellcome trust.

PMID- 15462766
TI  - Advances in the biochemistry of filariae.

PMID- 15462765
TI  - Wellcome Filariasis seminar '85.

PMID- 15462767
TI  - Advances in filarial chemotherapy and screening.

PMID- 15462769
TI  - Genes, vaccines and variation in malaria.

PMID- 15462768
TI  - Chemotherapy of malaria.

PMID- 15462770
TI  - Shellfish parasites.

PMID- 15462771
TI  - Snail collection to detect schistosome transmission sites.

PMID- 15462772
TI  - Cercariometry and the epidemiology of schistosomiasis.

PMID- 15462773
TI  - In vitro screens in the experimental chemotherapy of leishmaniasis and
      trypanosomiasis.
AB  - The search for more effective drugs for the treatment of leishmaniasis and
      trypanosomiasis has increasingly involved the use of in vitro screens. These
      possess the immediate advantages of requiring only a few mg of compound for
      tests, providing for a large through-put of compounds with rapid results at lower
      costs, and requiring fewer animals. Models for the cultivation or maintenance in
      vitro of 'mammalian stages' of Leishmania and Trypanosoma cruzi have been
      available for many years but only in the last decade have satisfactory techniques
      for the cultivation of bloodstream forms of T. brucei been developed.

PMID- 15462775
TI  - Ivermectin: fleas, fungi and pharmacology.

PMID- 15462774
TI  - Rats, mice and men - models for immune effector mechanisms against
      schistosomiasis.
AB  - Experimental studies have demonstrated the diversity of immune effector
      mechanisms against schistosomes. Among the various animal models, the rat appears
      as an excellent experimental system for investigation of antibody-mediated
      immunity to Schistosoma mansoni. Rat monoclonal antibodies have allowed the
      identification of effector and regulatory mechanisms operating in human
      infection, together with the characterization of protective antigens, leading to
      promising approaches to vaccine development.

PMID- 15462776
TI  - Fansidar-one man's warning.

PMID- 15462777
TI  - Is chagasic cardiopathy associated with HLA haplotype?

PMID- 15462778
TI  - Old world blowflies in the new world.
AB  - Human activity, particularly migration and the export of live animals, can
      provide vehicles for the dispersal of many parasites and their vectors. These
      movements, often overlooked until too late, provide potential for epidemic
      outbreaks and can profoundly alter accepted ideas on the geographic distribution
      and epidemiological status of particular species. In this review, Brian Laurence
      discusses the recent rapid spread of blowflies into the americas; these
      conspicious green flies transport a variety of gastro-intestinal pathogens
      between their favoured environments of latrines and exposed food, and some
      species are important parasites of flesh wounds, causing cutaneous myiasis.

PMID- 15462779
TI  - Chemotherapy of resistant falciparum malaria.

PMID- 15462780
TI  - Development of vaccines against equine helminths.

PMID- 15462781
TI  - Quantitative egg counts in schistosomiasis surveys.
AB  - Methods for urine filtration and quantitative egg counts play a key role in
      schistosomiasis surveys, but recent WHO recommendations may be misleading. In
      this article, Reny Braun-Munzinger working in Madagascar discusses technical
      problems in the use of nytrel filters for schistosome egg counts.

PMID- 15462783
TI  - Cell sorting by continuous flow cytometry.

PMID- 15462782
TI  - The molecular biology of schistosomes.
AB  - Investigators in various laboratories have been studying the molecular biology of
      schistosome genetics for several years. A recent meeting at the Marine Biological
      Laboratory in Woods Hole, Massachusetts, USA, sponsored by the Edna McConnell
      Clark Foundation, brought together 30 scientists from 16 laboratories to share
      what they have learned from their studies and debate strategies and techniques.

PMID- 15462784
TI  - Review of expert systems.

PMID- 15462785
TI  - Community participation in tsetse control.

PMID- 15462786
TI  - Schistosomiasis in Jordan: an unwelcomed guest.

PMID- 15462787
TI  - Zymodeme characterization of Trypanosoma cruzi.

PMID- 15462788
TI  - The complexity of Trypanosoma cruzi populations revealed by schizodeme analysis.

PMID- 15462789
TI  - Liposomes as drug carriers in leishmaniasis and malaria.
AB  - Experimental studies suggest that liposomes could substantially improve the
      performance of anti-leishmanial drugs in the chemotherapy of visceral
      leishmaniasis. In this article, Carl Alving discusses the potential for
      overcoming resistance to antimonial drugs; for 'buffering' the toxicity of drugs,
      and for drug delivery under conditions where hospitalization is impossible or
      inconvenient. Liposomes can also be used experimentally to reduce the toxicity
      and increase the efficacy of parenterally-administered primaquine in the
      treatment of sporozoite-induced murine malaria.

PMID- 15462790
TI  - Replicating helminth parasites of man.
AB  - Most helminth parasites of man are unable to replicate within the human host.
      Thus, the worm burden of an infected person (on which the pathology largely
      depends - see Box 1) is a function of the number of infective forms to which the
      person is exposed. But for some species of helminths, the ability to replicate in
      man has a marked effect on the course and duration of infection, and for the
      pathogenesis of disease. In this review, David Grove discusses the mechanisms by
      which such replication may occur, and considers how this ability affects our
      approach to therapy and control.

PMID- 15462791
TI  - Progress in warble fly eradication.
AB  - Warble flies (Fig. 1) are bee-like insects, belonging to the parasitic fly family
      Oestridae, which spend their entire 10-month larval period inside the body of the
      host animal, only emerging in the summer to complete their development to the
      free-flying adult stage (Fig. 2). In 1978, when almost 40% of cattle in Britain
      were infested, the Ministry of Agriculture, Fisheries and Food (MAFF) initiated a
      warble fly eradication scheme. We are now in the final stages of this plan, with
      infestation rates down to 0.01%. This represents a massive saving to the farming
      industry in terms of less damaged hides and improved production of milk and beef.
      It also represents an enormous improvement in animal welfare; cattle in the past
      often carried 20-30 of these large (2 cm long) grubs in pus-filled 'warble' lumps
      on their backs. Now they are never seen in most parts of the country. In this
      review, David Tany discusses the progress of warble fly control, warning that the
      problem could reappear unless stringent measures are taken o eradicate remaining
      foci and o control imported cattle.

PMID- 15462792
TI  - Mozart's death attributed to parasitism.
AB  - Among the uncertainties surrounding the life of Mozart, few have been the subject
      of as much speculation as the matter of the composer's final illness and death.
      The debate has often seemed somewhat pointless, because direct medical evidence
      has been lacking and, since the body was buried in an unmarked gravesite, is
      likely to remain lacking. Indirect or circumstantial evidence, however, can
      contribute to an understanding of the matter, and it is the purpose of this
      communication to call attention to the discovery of an unexpected piece of
      circumstantial evidence which throws an entirely new light on the subject.

PMID- 15462793
TI  - The hazard of malarial nephropathy.
AB  - Renal damage in malaria occurs as a result of two distinct mechanisms:
      microcirculatory disturbance, which is confined to falciparum malaria, and
      immunological damage through the deposition of soluble immune complexes. Quartan
      malarial nephropathy, due to Plasmodium malariae, is a progressive disease ending
      in chronic, hypertensive, renal failure. The disease seems most prevalent in
      adolescents, placing a heavy burden on the health services of developing
      countries where falciparum malaria is endemic.

PMID- 15462795
TI  - Autoimmunity should not limit the search for a Chagas disease vaccine.

PMID- 15462796
TI  - Enhanced chemiluminescent enzyme immunoassays.

PMID- 15462797
TI  - Dipping to control vectors of cattle parasites.

PMID- 15462798
TI  - Tsetse control by autosterilization.

PMID- 15462799
TI  - Immunogenicity assays for clinical trials of malaria vaccines.

PMID- 15462800
TI  - Is new world onchocerciasis spreading?

PMID- 15462801
TI  - Prospects for vaccine against Schistosomiasis.

PMID- 15462802
TI  - Irridiated schistosome vaccines.

PMID- 15462803
TI  - Advances in pneumocystis biology.

PMID- 15462804
TI  - Surface antigens of African trypanosomes in the tsetse fly.

PMID- 15462806
TI  - Is Trypanosoma brucei an intracellular parasite?

PMID- 15462805
TI  - Double development cycle of Trypanosoma cruzi in the opossum.

PMID- 15462807
TI  - Macrophage-parasite interactions in vitro: potential use of extracellular matrix.

PMID- 15462808
TI  - Indigestible phytoplankton for mosquito control.

PMID- 15462809
TI  - Immunoassays of malaria sporozoites in mosquitoes.

PMID- 15462810
TI  - The case for mathematical modelling of schistosomiasis.
AB  - Large problems, such as the large-scale transmission of parasitic disease, are
      complex and difficult to predict. Understanding them, in order to make cost
      efficient choices about possible control interventions, requires knowledge from a
      very wide range of specialists. Modelling the system can help to do this, but
      must not ignore the specific requirements of administrators and executives who
      have to work with high-level decisions about disease control. To many, the
      modelling approach seems arcane and divorced from reality, unable to answer the
      decision-makers. But techniques are improving, and in this article, Norman Bailey
      puts the case for the mathematical modelling of schistosomiasis.

PMID- 15462811
TI  - Hydatidosis: changing concepts in epidemiology and speciation.
AB  - Hydatidosis, caused by dog tapeworms of the genus Echinococcus, is one of the
      most important cestode infections of man. It is widely distributed and recent
      information points to a spread of the disease into areas previously free of it.
      This article reviews recent advances in understanding the biology of
      Echinococcus, relating these developments to the epidemiology of hydatid disease
      and its control.

PMID- 15462812
TI  - Immunological approaches to the control of animal trypanosomiasis.
AB  - Control of African trypanosomiasis relies heavily on attempts to eliminate the
      tsetse fly vectors, and the use of trypanocidal drugs which are not entirely
      satisfactory. But the prospects for immunological control have a long history -
      since the last century, explorers and settlers in Africa have progressively
      exposed their horses and cattle to tsetse bites (a process known as 'salting') in
      an attempt to build up some degree of immunity to the disease. More recently,
      immunologists and biochemists have used modern techniques to explore the
      possibility of suitable vaccines. In this article, Vinand Nantuyla discusses the
      problems and possible contributions of the immunological approach.

PMID- 15462814
TI  - Sandfly diet and Leishmania.

PMID- 15462813
TI  - The role of interferons in parasitic protozoan infection.
AB  - Interferons are well-known for their role as a first line defence against viral
      attack, but they also modulate the host immune system in responses to protozoan
      infections. In this article, John Kelly explains what interferons are, and
      discusses their potential role against parasitic infection.

PMID- 15462816
TI  - Cuticular hydrocarbons distinguish sibling species of vectors.

PMID- 15462815
TI  - Microtubular cytoskeletons of parasitic protozoa.
AB  - Shape, motility and division of eukaryotic cells are all determined to some
      extent by intracellular microtubules. Parasites, particularly protozoan
      parasites, offer important models for the study of microtubule organization,
      which may also provide useful leads for novel chemotherapeutic agents against
      parasite-specific forms of these organelles. Research on the biology of
      microtubules has advanced rapidly in the last 2-3 years, from purely descriptive
      studies to on understanding of some of the genetic and biochemical aspects. In
      this article, David Russell and Jean-Francois Dubremetz summarize the progress
      and discuss the potential of tubulin as a drug target for antiprotozool
      chemotherapy.

PMID- 15462817
TI  - Discovery and control of primary amoebic meningoencephalitis (PAM).

PMID- 15462818
TI  - Molecular vaccines against parasites.
AB  - Prophylactic vaccines can be expected to be one of the major practical outputs of
      parasitology research. Various groups within Australia have pursued the vaccine
      objective for several years, with particular emphasis on blood-stage falciparum
      malaria in man, intestinal helminths of sheep and cattle, cutaneous myiasis
      (blowfly strike) in sheep, cysticercosis in sheep and cattle, bovine babesiosis,
      and cattle ticks. Other vaccine programmes are concerned with giardiasis,
      filariasis, toxoplasmosis, fascioliasis, coccidiosis in poultry, cutaneous
      leishmaniasis and schistosomiasis japonica. For many years, the only available
      vaccine against a parasite in Australia has been the attenuated Babesia bovis
      vaccine produced by the Tick Fever Research Centre of the Queensland Department
      of Primary Industries. Strategies for achieving molecular vaccines are generally
      similar within the various research groups. They involve analysis of the
      immunology and immunochemistry of a model or in-vitro system; development of
      functional monoclonal antibodies; analysis of antibody specificities in
      clinically and/or functionally defined polyclonal sera; screening of cDNA or
      genomic expression libraries; peptide synthesis; identification of an appropriate
      vaccination schedule involving adjuvants or new recombinant DNA-based antigen
      delivery systems. Outlined below are five of the major vaccine programmes.

PMID- 15462819
TI  - Non-antibody immunity against malaria.

PMID- 15462820
TI  - Allozyme electrophoresis and the genetic characterization of parasites.

PMID- 15462821
TI  - Onchocerciasis research in North Queensland.

PMID- 15462822
TI  - Anthelmintic resistance in Australia.

PMID- 15462823
TI  - Dormancy in nematode infections.

PMID- 15462824
TI  - Insecticide resistance in veterinary ectoparasites.

PMID- 15462825
TI  - Can parasites be used to control 'mouse plagues'?

PMID- 15462826
TI  - Parasites and parasitologists 'Down Under'.

PMID- 15462828
TI  - Remarkable parasites in a unique host.

PMID- 15462827
TI  - Marine parasitology in Australia.

PMID- 15462829
TI  - Parasitology in CSIRO.

PMID- 15462830
TI  - Biogeography of parasites in Australia.

PMID- 15462831
TI  - Pioneers of Australian parasitology.

PMID- 15462832
TI  - Medical parasitology in Australia.

PMID- 15462833
TI  - Sex and the single trypanosome.

PMID- 15462834
TI  - Mast cell responses to helminth infection.
AB  - Mast cells have been suggested to be major effector cells in the immune response
      to infection with helminths. It is now clear, however, that mast cells are
      heterogeneous and have a diversity of important functions. In this review,
      Timothy Lee, Mark Swieter and Dean Befus point out that much of the confusion
      about the role of mast cells in immunity stems from methods and interpretations
      which are inadequate for the diversity of roles played by these cells in host
      responses to parasites. Classical histochemistry may fail to reveal active mast
      cells, and studies using chemical antagonists are difficult to interpret until we
      know more about the action of the drugs. The authors show that current research
      is extending our knowledge of mast cell heterogeneity, and helping to define the
      powerful array of mediators that they can use to orchestrate the immune response
      to helminth infections.

PMID- 15462835
TI  - Chronobiology of schistosome development in the snail host.

PMID- 15462837
TI  - Why vaccines do not work in Chagas disease.

PMID- 15462836
TI  - Immunology of scabies.

PMID- 15462838
TI  - Immunological detection of parasite antigen in faeces.

PMID- 15462839
TI  - Urban drainage in developing countries.

PMID- 15462840
TI  - Vectorial capacity: must we measure all its components?
AB  - Following attack on an insect vector-perhaps with insecticide or by removing
      breeding sites-we need to know what reduction in disease can be expected. In
      general, reliable predictions of the epidemiological consequences of any
      entomological change are highly desirable. Such predictions require a measure of
      the capacity of an insect population to transmit disease. A popular approach is
      to try to quantify all the entomological components of transmission, in isolation
      from the parasitological components, and then calculate the maximum daily
      reproductive rate of the disease-known as the Vectorial Capacity. But to measure
      accurately all the entomological components is technically demanding. In this
      article, Chris Dye argues that epidemiological predictions could be made by
      including only the dominant entomological variables in an index-a streamlined
      Vertical Capacity-which can then be fine-tuned by closely matching entomological
      and parasitological observations.

PMID- 15462841
TI  - Biology of babesia.
AB  - Recent advances in the knowledge of the biology of the protozoan family
      Babesiidae is reviewed with special emphasis on those species which cause
      economically important diseases in cattle. The life cycle of Babesia of cattle is
      illustrated taking into account these recent advances. Areas of controversy in
      the life cycles still exist particularly over the presence or absence of a sexual
      cycle within the tick vector and of exoerythrocytic schizonts in the mammalian
      host. In the mammalian host, the major parasite division cycle occurs in
      erythrocytes and it is these stages which induce the pathogenic effects. The
      recent progress in the understanding of the biology of Babesia parasites may
      allow important developments in the control of babesiosis.

PMID- 15462842
TI  - Fluorochrome-labelled lectins reveal secreted glycoconjugates of schistosome
      larvae.

PMID- 15462843
TI  - Molecular pharmacology of protozoan parasites.

PMID- 15462845
TI  - A filter immunoplaque assay for quantification of parasite-specific antibody
      producing cells.

PMID- 15462844
TI  - Difiuoromethylornithine in the treatment of African trypanosomiasis.

PMID- 15462846
TI  - Mosquito control with larvivorous fish.

PMID- 15462847
TI  - Control of chicken coccidiosis.
AB  - Coccidiosis could potentially cause enormous economic loss to the poultry
      industry, especially in the production of broiler chickens (see Box 1). Losses
      are currently minimized by chemotherapeutic treatment but the effectiveness of
      many drugs seems to be declining. In this article, Peter Long and Tom Jeffers
      discuss the future for coccidial chemotherapy, and the potential for
      immunological control methods.

PMID- 15462848
TI  - Strongyloides stercoralis: immunobiological considerations on an unusual worm.
AB  - In the highly competitive world of parasites, where survival is indissolubly tied
      to the presence of suitable hosts in the same ecological niche, Strongyloides
      stercoralis occupies a unique position. This versatile nematode has developed a
      successful relationship with two ecosystems, the terrestrial environment and the
      mammalian body, by becoming facultatively independent of either (Box 1). It
      requires external maturation for transmission, but it also has the ability to
      multiply within a single host. It prefers man, but may infect apes, monkeys, dogs
      and cats. As a human parasite, S. stercoralis establishes self-perpetuating
      intestinal colonies and negotiates their survival with the host's defense
      mechanisms. In this article, Robert Genta reviews the immunobiological aspects of
      this unusual relationship.

PMID- 15462849
TI  - Epidemiology of scabies.

PMID- 15462850
TI  - Chicken house reservoirs of sandflies.

PMID- 15462851
TI  - Vectorial capacity.

PMID- 15462852
TI  - Kudos to the editor.

PMID- 15462853
TI  - Intrascrotal development of trypanosomes.

PMID- 15462854
TI  - Current approaches to malaria chemotherapy and prophylaxis.
AB  - Malaria continues to be one of the most serious and widespread parasitic
      diseases, still occurring in over 100 countries despite concentrated efforts to
      eradicate it from many regions. Sixty-one countries now report their malaria
      cases to the WHO, and the latest analysis of these figures' shows little
      improvement in the overall problem during the last 15 years. Some countries,
      notably India and China, continue to report downward trends, but the problem
      continues to deteriorate in rural areas where intense economic development is
      taking place, particularly in Asia and the Americas. In 1984, 5.3 million cases
      of malaria were reported to the WHO. This is believed to represent but a small
      fraction of the total number because, for example, 38 of the tropical African
      countries do not report their malaria cases. Estimates based on the degree of
      malaria endemicity suggest a total incidence o f around 100 million cases
      annually. Chloroquine-resistant falciporum malaria has been confirmed in more
      than 40 countries, often showing cross-resistance to other drugs, and attempts to
      combat resistance using combination drugs have led to disturbing reports of side
      effects as well as multidrug resistance. Vector control is also impaired in many
      areas due to insecticide resistance. Faced with these problems, we asked Dr
      Walther Wernsdorfer, head of the WHO Malaria Action Programme, what is the
      current WHO philosophy of malaria chemotherapy and prophylaxis?

PMID- 15462855
TI  - Raccoon ascarids as a cause of larva migrans.

PMID- 15462856
TI  - Will the real Trypanosoma b. gambiense please stand up.
AB  - Controversy has surrounded the differentiation of Trypanosoma brucei gambiense
      from T. b. rhodesiense (causative agents of Gambian and Rhodesian sleeping
      sickness, respectively) almost from the moment they were named. In the light of
      recent findings from biochemical and immunological characterization studies,
      Wendy Gibson reviews the status of T. b. gambiense to see if there is now a
      consensus concerning its identity.

PMID- 15462857
TI  - The control of schistosomiasis - is a vaccine necessary?

PMID- 15462858
TI  - In vitro cultivation of Sarcocystis merozoites.

PMID- 15462859
TI  - Immunization to control East Coast Fever.

PMID- 15462861
TI  - Tick control in the context of ECF immunization.

PMID- 15462862
TI  - Immunity in human schistosomiasis.
AB  - Field studies on immunity in human schistosomiasis are expensive, labour
      intensive and extremely time-consuming, requiring many years to yield even
      provisional results. In this review, Anthony Butterworth and Paul Hagan summarize
      the need for such studies, the evidence for immunity in man, the immunological
      factors that may govern the expression of immunity, and the implications of such
      work for the development of new methods of control through vaccination.

PMID- 15462863
TI  - Sarcocystosis.
AB  - Sarcocystis infections of animals are commonplace and of worldwide distribution.
      Some species can be severely pathogenic to farm animals, causing anorexia, weight
      loss, abortion and even death. But perhaps because sarcocysts are so common they
      have frequently been regarded as innocuous. Even in the USA and UK, many cases of
      abortion in farm animals go undiagnosed, and it is only now that sarcocystosis is
      being implicated as potentially of economic importance to the farm industry. In
      many cases however, the major effect is likely to be subclinical, seen in farm
      animals only as a reduction in liveweight gain. As this review shows, the history
      of research on Sarcocystis has been marked by confusion and neglect, although
      enormous progress has been made in the last decade. But until their economic
      importance is fully recognized, these widespread infections seem likely to
      continue unchallenged.

PMID- 15462864
TI  - The economics of schistosomiasis chemotherapy.
AB  - The optimal choice o f chemotherapy regime arises in the design o f every
      schistosomiasis control programme. This choice is o f particular contemporary
      interest for two reasons. At one extreme the development of effective single-dose
      oral drugs such as praziquantel and oxamniquine makes mass chemotherapy a
      practical option. At the other extreme there has been a revival o f advocacy for
      some form o f selective treatment. But all developing countries that contemplate
      schistosomiasis control face severe budget constraints, requiring careful
      analysis o f the economics o f chemotherapy. In this article, Nick Prescott
      presents a generalized framework For resource allocation in schistosomiasis
      chemotherapy, demonstrating that the optimal choice o f chemotherapy regime
      depends critically on the level of budget constraint, the unit costs o f
      screening and treatment, and rates o f compliance with screening and chemotherapy
      all factors which are usually neglected in the choice o f control strategy.

PMID- 15462865
TI  - Monoclonal antibodies for immunodiagnosis of human hydatidosis.

PMID- 15462866
TI  - Progress towards a defined vaccine for schistosomiasis.
AB  - During the last five years considerable progress has been made in studies o f
      schistosome immunology. Convergent views have emerged from the study of human and
      animal immunity which agree on the mechanisms required and the antigens involved.
      The reproducible induction of protective immunity with attenuated parasites and
      with antigenic preparations has now led to agreement that vaccination against
      schistosomiosis is on achievable goal. The evidence that led to this optimistic
      view was reviewed at a scientific working group on 'Prospects for Immunological
      Intervention in Human Schistosomiosis' held in Geneva in May 1986, under the
      auspices of the UNDP/World Bonk/WHO Special Programme.

PMID- 15462868
TI  - Radiological diagnosis of neurocysticercosis.

PMID- 15462867
TI  - Production of parasite antigen by co-transformation.

PMID- 15462869
TI  - Control of opisthorchiasis through community participation.

PMID- 15462870
TI  - Progress in in-vitro culture of the malaria life cycle.

PMID- 15462871
TI  - Antigen presentation and the response to parasitic infection.
AB  - Antigen presentation to T-cells is central to the induction and maintenance of
      the cell-mediated immune response. Many approaches have been used to define a
      complex accessory cell compartment, which performs the variety of functional
      roles encompassed by this term. Resulting from this, antigen presentation has
      become the cornerstone behind many theories of disease susceptibility and is an
      important consideration for vaccine design. In this article, Paul Kaye reviews
      aspects of antigen presentation by accessory cells with particular emphasis on
      how parasites and their antigens interact with this heterogeneous group of cells.

PMID- 15462872
TI  - Cell-mediated immunity in protection and pathology of malaria.
AB  - The stimulation of protective immunity against malaria is the goal of many
      research groups. But trials with antigens that stimulate antibodies have yet to
      fulfil these expectations, and it is increasingly recognized that non-antibody
      mediated immunity is also important in immunity to malaria - especially through
      mediators such as gamma interferon, tumour necrosis factor and reactive forms of
      oxygen. However, the host can suffer if this type of immune response is too
      exuberant, and in this review, Ian Clark argues that much of what is recognized
      as clinical malaria is caused in this way. He suggests that only when discussed
      in these terms can malaria illness and pathology be seen as a coherent,
      predictable entity instead of a sea of unconnected surprises. Moreover, these
      ideas have important implications for vaccine development that, although
      requiring more basic work, must not be neglected.

PMID- 15462873
TI  - Predator-prey interactions between ectoparasites.
AB  - Vertebrates represent a resource frequently exploited by ectoparasites. But the
      ectoporosites themselves also represent a resource that can be exploited by
      specialized predators. Some o f these predators have been classified as
      ectoparasites, but in some cases the vertebrate blood in their crops comes from
      their blood-sucking prey. In fact, as Lance Durden explains, the assemblage o f
      arthropods that inhabit the vertebrate skin surface, or pelage, seems to show a
      complete spectrum of adaptations from predators to facultative and obligate blood
      suckers, together with those feeding on other materials in this special habitat.
      The dynamics of their interactions are further complicated by responses of the
      host to the arthropods, and much further study is needed before the role o f
      predators in controlling ectoparasites can be clarified.

PMID- 15462874
TI  - Control of lymphoproliferation by Theileria annulata.
AB  - The economic importance of bovine theilerioses has prompted several new
      approaches to understanding the diseases in the hope of developing more efficient
      methods of control. Most Theileria species that infect cattle cause a lymphoproli
      ferative disease. Sporozoites, injected into the host bloodstream by the tick
      vectors, rapidly invade host lymphocytes and stimulate rapid division of infected
      cells. As these rupture, merozoites are released which invade red blood cells
      ready to infect feeding ticks again. The process by which Theileria parasites can
      control host lymphocytes, and induce them to divide in synchrony with the
      parasites themselves, is poorly understood but seems to be the key to
      pathogenesis. In this article, Michael Dyer and Andrew Tait discuss the possible
      mechanisms of cellular control in the light of recent work revealing sequences
      homologous to oncogenes in the DNA of T. annulata.

PMID- 15462875
TI  - Trypanothione metabolism: a chemotherapeutic target in trypanosomatids.
AB  - Chemotherapy of trypanosomotid infections continues to present challenges.
      Treatment of Trypanosoma cruzi infections is virtually impossible, while
      treatment of Leishmaniasis and African tryponosomiasis is, at best, difficult -
      often involving toxic drugs based on heavy metals such as antimony and arsenic.
      As with several other parasites, much recent research has focused on defining
      metabolic differences between parasite and host that could represent good targets
      for chemotherapy. As Graeme Henderson and Alan Fairlamb explain, there is
      something strange about glutothione in trypanosomotids - which seems to offer a
      very promising chemotherapeutic target.

PMID- 15462876
TI  - Rapid characterization of recombinant lambdagt11 clones expressing parasite
      antigens.
AB  - Recombinant DNA techniques allow any parasite gene to be isolated, propagated and
      analysed in great detail. The techniques are now well known and widely used in
      research on parasite diagnosis, vaccine development and identification of
      chemotherapeutic targets. There are difficulties, for example in analysing
      carbohydrate antigens, and in selecting which genes merit the intensive
      investigation required. In this article john Kelly and Mark Blaxter discuss two
      simple procedures that allow recombinant clones to be characterized rapidly on
      the basis of both the parasite DNA sequences that they carry and the parasite
      antigens that they produce. They take examples from work on antigens of
      Leishmania donovani.

PMID- 15462877
TI  - Ecological mapping to support mosquito control on the French Mediterranean coast.
AB  - Less than a century ago on the French Mediterranean coast, mosquitoes were
      responsible for a high rate of mortality from malaria. Today, mosquitoes are no
      more than a nuisance, but mosquito control is carried out actively to protect
      local residents and the economically important tourist trade. Along the
      Mediterranean coast, mosquito control makes use of environmental management:,
      biological control and insecticides. However, by use of detailed ecological maps,
      these control activities can be accurately targeted, leading to efficient
      control, reduced costs and minimal likelihood of insecticide resistance. In this
      article, Andre Gobinoud explains these techniques.

PMID- 15462878
TI  - Myxosporea: a new look at long-known parasites of fish.
AB  - With the identification of Myxosporea as agents of swimbladder inflammation (SBI)
      in carp, and proliferative kidney disease (PKD) in salmonids, this group of over
      1000 protistan species has been receiving renewed attention. Almost all species
      are parasites offish, and some can cause serious losses in commercial fish farms.
      Yet adequate control measures cannot be planned without clarification of basic
      features of the parasites' life cycles and modes of transmission. In this
      article, Jiri Lom reviews progress in understanding these biological puzzles.

PMID- 15462879
TI  - Treatment and prophylaxis for Pneumocystis carinii pneumonia.
AB  - Without treatment, Pneumocystis carinii pneumonitis is almost always fatal in the
      immunocompromised host. Here, Walter Hughes discusses proven and potential
      treatments, and methods of chemoprophylaxis in high-risk patients. Two drugs,
      pentamidine isethionate and trimethoprimsulfamethoxazole, are equally effective
      therapeutically - permitting the recovery of approximately 75% of patients - but
      the latter drug combination is preferred because of its lower toxicity and fewer
      adverse effects. The pneumonitis can be prevented by prophylactic administration
      of trimethoprim-sulfamethoxazole. Other drugs with proven efficacy or under study
      include Fansidar, dapsone, trimetrexate and difluoromethylornithine.

PMID- 15462880
TI  - Control of Chagas disease in Brazil.
AB  - Chagas disease (South American trypanosomiasis) is a chronic but often fatal
      disease endemic throughout much of Latin America. Serological surveys suggest
      around 24 million people seropositive for the causative agent, Trypanosoma cruzi
      (Fig. 1), with over 65 million living in the endemic areas and at risk to
      infection. In Brazil, over 25 million people are considered at risk, and control
      of the disease constitutes one of Brazil's public health priorities. Treatment or
      vaccination against T. cruzi is impossible at the public health level because
      suitable drugs or vaccines are not available. But it is well recognized that
      transmission can be interrupted by eliminating the domestic vectors - blood
      sucking reduviid bugs of the subfamily Triatominae. In Brazil, eradication of
      Triatoma infestans - the major domestic vector of T. cruzi - is now seen as a
      feasible target by the Ministry of Health. However, although other domestic
      vectors can also be controlled, they will retain their sylvatic ecotopes from
      which they can reinvade houses. In this article, Joao Carlos Pinto Dias explains
      the current Brazilian policy, high-lighting the successful elimination of T.
      infestans from much of the southern part of the country.

PMID- 15462881
TI  - Trematode eggshells: Novel protein biopolymers.
AB  - In the past few years recombinant DNA technology has somewhat serendipitously
      shed new light on the formation of trematode eggshells, with the publication of
      the sequences of highly expressed female-specific genes encoding protein
      components of the schistosome eggshell and with the isolation of DOPA-rich
      proteins and one of the corresponding genes from Fasciola. These proteins and
      other structural polypeptides with repetitive structures were the subject of a
      recent meeting Bioengineering for Material Applications (sponsored by the Office
      of Naval Research in Bethesda, USA, June 1987). In this article, based on that
      meeting, John Cordingley explains how the structure of trematode eggshells
      appears to show features common to several other biopolymers.

PMID- 15462882
TI  - Cachectin--Tumour necrosis factor: a cytokine that mediates injury initiated by
      invasive parasites.
AB  - The primary role for which the immune system evolved was a protective one, yet
      there is no doubt that immune mechanisms can also injure the host. Frequently
      cited examples of immune-mediated injury include complement-induced disease
      processes, diseases caused by immune complexes, or those that result from cell
      mediated hypersensitivity. During the past few years however, it has become clear
      that the immune system can also express itself through the action of various
      cytokines. Gradually, it has been appreciated that these agents may cause disease
      when produced excessively or inappropriately, and in this article Bruce Beuder
      and Anthony Cerami discuss one of the most important of these cytokines -
      cochectin or tumour necrosis factor (TNF).

PMID- 15462883
TI  - Plerocercoid growth factor: a homologue of human growth hormone.
AB  - Plerocercoids of the tapeworm, Spirometra mansonoides, produce a factor with
      characteristics similar to those of mammalian growth hormone (GH). Plerocercoid
      growth factor (PGF) stimulates growth and mimics other actions of GH but does not
      possess the anti-insulin/diabetogenic activities intrinsic to mammalian growth
      hormones. Duplication of activities unique to human GH, chemical and physical
      similarities, plus crossreactivity with strictly specific anti-hGH monoclonal
      antibodies, underlie the hypothesis that S. mansonoides has obtained and
      expresses a human gene for GH. In this article, Kirk Phares discusses the
      similarities between the two hormones.

PMID- 15462884
TI  - The potential for drug resistance in schistosomiasis.

PMID- 15462885
TI  - Schistosome economics.

PMID- 15462887
TI  - Entamoeba histolytica: zymodeme and pathogenicity.

PMID- 15462888
TI  - Entamoeba histolytica: is it necessary to characterize pathogenic strains?

PMID- 15462891
TI  - Parasites of the Christmas turkey.
AB  - In the temperate West, the turkey remains popular fare for festive feasts. It is
      a large bird, amenable to intensive rearing, and now represents one of the
      cheapest forms of poultry meat available (Box 1). In the USA alone, nearly 100
      million birds are raised annually - mainly in Minnesota and North Carolina. But
      intensive rearing can incur risks of epizootic parasitic diseases, often
      responsible for severe economic losses. Improved management and medication have
      reduced the impact of some, such as 'gapezvorm disease', histomoniasis and
      intestinal coccidiosis; leucocytozoonosis now presents less of a threat than in
      the past, but some 'newer' diseases such as cryptosporidiosis may yet present
      severe problems. In this article, Peter Long, William Current and Gayle Noblet
      review the main parasite challenges faced by the commercial turkey industry.

PMID- 15462892
TI  - Public health importance of Angiostrongylus cantonensis and its relatives.
AB  - Species of Angiostrongylus are fairly common nematode parasites of a variety of
      small mammals, but some species - particularly A. cantonensis and A.
      costaricensis - are increasingly seen as human infections. The worms make use of
      a range of aquatic, amphibious or terrestrial gastropod molluscs as intermediate
      hosts, which become infected by ingestion of eggs shed in the faeces of infected
      mammals. Porotenic hosts, including crustaceans, amphibians and reptiles, are
      known for most Angiostrongylus species, and can also be a source of the infective
      third-stage larvae that initiate mammalian infections.

PMID- 15462895
TI  - More gene libraries and more operational research.

PMID- 15462894
TI  - Interaction of malaria with mosquitoes.

PMID- 15462896
TI  - Trypanosome species-specific DNA probes to detect infection in tsetse flies.

PMID- 15462897
TI  - Detection of South American trypanosomes in insects using total parasite DNA
      probes.

PMID- 15462898
TI  - DNA probes to identify Onchocerca volvulus.

PMID- 15462899
TI  - Highly repeated DNA sequences as species-specific probes for Brugia.

PMID- 15462900
TI  - Probing the unknown.

PMID- 15462901
TI  - DNA hybridization assays for detection of malarial sporozoites in mosquitoes.

PMID- 15462902
TI  - Rural housing for control of Chagas disease in Venezuela.
AB  - The home is an important protective element for the health of its inhabitants -
      but these inhabitants often include not only the householders but also domestic
      pests and vectors of disease. This is particularly so in Latin America where
      domestic triatomine bugs thrive in many of the poorer quality rural houses,
      emerging from their crevices at night to feed and transmit Trypanosoma cruzi in
      their faeces. At the public health level, there is neither drug nor vaccine
      suitable for controlling T. cruzi - causative agent of Chagas disease - but
      transmission can be interrupted by control of the domestic vectors.
      Traditionally, vector control has involved spraying houses with residual
      insecticides, but a more long-term solution, with many colateral benefits, is to
      improve rural housing in such a way that colonization by triatomine bugs is
      inhibited. Such an approach involves development of low-cost techniques for house
      construction, and mobilization of rural communities to make use of them. In this,
      Venezuela has played a leading role, as Roberto Briceno-Leon reports.

PMID- 15462903
TI  - Effect of culture conditions and bacterial associates on the zymodemes of
      Entamoeba histolytica.

PMID- 15462904
TI  - The reliability of Entamoeba histolytica zymodemes in clinical diagnosis.

PMID- 15462905
TI  - Anisakiasis - is the sushi bar guilty?
AB  - Since 1972, Japan and some other countries such as the USA have seen a sudden
      increase in cases of anisakiasis (infection with Anisakis sp.) and codworm an
      isakiasis (infection with the codworm, Pseudoterranova [= Phocanema] decipiens).
      Larval stages of these nematodes occur in the muscles of a variety of fish and
      squid, and ingestion of raw and undercooked fish or squid is the prime route of
      human infection. Thus the Japanese style of eating sashimi (sliced raw fish
      fillet) and the increasing popularity of sushi bars where such dishes are served,
      has often been suggested as contributing to the spread of anisakid infections. In
      this article, Tomoo Oshima discusses the current status of anisakiasis and
      codworm anisakiasis, showing that the apparent increase in human cases is related
      more to advances in diagnosis than to the commercialization of sushi.

PMID- 15462906
TI  - Trypanosoma (Duttonefla) vivax.
AB  - Although Trypanosoma vivax was first discovered in 1905 (Ref. 1), the fact that
      most stocks of this parasite are restricted to ruminant hosts has retarded
      investigation of this species compared with the experimentally more amenable T.
      brucei and T. congolense. The veterinary importance of T. vivax (Box 1) and a
      recent report suggesting that T. vivax may have an even more extended range than
      previously thought (Box 2) prompts an evaluation of the current knowledge of the
      biology of this trypanosome.

PMID- 15462907
TI  - Malaria invasion of human erythrocytes.
AB  - The invasion of human red blood cells (RBC) by plosmodiol merozoites is a key
      event during malaria infection, and the inhibition o f invasion is regarded as a
      crucial goal of malaria vaccine development. For Plasmodium falciparum it has
      been suggested that the red cell sialoglycoproteins, glycophorins A, B and C, are
      receptors for invasion and that O-linked or N-linked carbohydrate structures may
      be involved as receptor sites(1-3). However, recent evidence suggests that the
      role o f these sialoglycoproteins and carbohydrates may have been overestimated.
      In this article, Peter Hermentin discusses the contradictory findings and
      presents a revised model for the invasion process.

PMID- 15462908
TI  - Helminth fecundity: density dependence or statistical illusion?
AB  - Density-dependent constraints on fecundity or survival are critical for the
      regulation and stability o f all populations. Helminth parasites are no exception
      to this rule. In medical helminthology, it has been widely assumed that the most
      effective density-dependent constraints act upon parasite fecundity and are the
      result of intra-specific parasite competition or acquired immunity to infection.
      In this article, Anne Keymer and Andrew Slater advocate a more detailed
      examination of the evidence on which this assumption rests.

PMID- 15462909
TI  - Why is ringworm called ringworm?

PMID- 15462910
TI  - Non-lymphokine mediated antileishmanial defence.

PMID- 15462911
TI  - Molecular weight separation of very large DNA.
AB  - Gel electrophoresis has many applications in parasitology, especially for the
      separation of enzymes, immunoglobulins and DNA, but the ability to separate
      molecules based on size is usually restricted to within the upper and lower
      ranges o f molecular weight. These limitations are particularly evident in
      mocromolecular DNA electrophoresis, although recent innovations in ogorose gel
      electrophoresis have substantially reduced these boundaries and are permitting
      the separation of very large DNA molecules and intact chromosomes of many
      organisms. In this article, Hugh Dawkins explains these techniques and their
      principle variants.

PMID- 15462912
TI  - Wanted: entrepreneurial parasitologists.
AB  - At the recent World Water '86 conference in London, the Director of Water Supply
      and Urban Development in the Operations Policy Department of the World Bank
      chastised the assembled engineers for behaving like religious fanatics, convinced
      that their work is good and righteous but not willing (or able) to demonstrate
      this. There must be an opening here for an entrepreneurial parasitologist.

PMID- 15462913
TI  - Sheep strike and mulesing.

PMID- 15462914
TI  - The role of molluscicides in schistosomiasis control.

PMID- 15462915
TI  - Focal mollusciciding: an effective way to augment chemotherapy of
      schistosomiasis.

PMID- 15462916
TI  - Immunological responses to parasitic arthropods.
AB  - Parasitic arthropods are responsible for enormous economic losses to livestock
      producers throughout the world. These production losses may range from simple
      irritation caused by biting and non-biting flies to deaths and/or damage to
      carcass, fleece, or skin resulting from attack by myiasis flies. The estimated
      costs of these losses are colossal but even these usually include only direct
      losses and ignore those associated with pesticide application. In the USA alone
      (in 1976), these losses were conservatively estimated at more than 650 million US
      dollars. The long term use of chemical control measures for these pests has
      resulted in many serious problems including residues in meat and milk products,
      rapid development of insecticide resistance, the destruction of non-target
      organisms, environmental pollution, and mortality and morbidity of livestock.
      These concerns have prompted researchers to seek alternative methods of arthropod
      control, including the artificial induction of immunity. In this review, R. W.
      Baron and J. Weintraub discuss several examples of ectoparasites that can induce
      immunological resistance in the host, including Sarcoptes and Demodex mites, the
      sheep ked (Melophagus ovinus), Anopluran lice and myiasis-causing flies such as
      Hypoderma.

PMID- 15462917
TI  - Haemoglobinopathies and malaria: new approaches to an old hypothesis.
AB  - It is almost 40 years since Haldane proposed that high frequencies of
      thalassaemia and other hoemoglobinopathies might result because these genetic
      disorders conferred some protection against malaria In the intervening years
      convincing clinical, epidemiological and in vitro data have been produced to
      support this 'malaria hypothesis' for haemoglobin S. However, for the numerous
      other genetic disorders of haemoglobin that are suspected to have been selected
      in this way it has been much more difficult to provide clearcut evidence. For
      example, in the case of beta-thalassaemia some but not all epidemiological
      studies support the hypothesis, while in vitro studies have failed to demonstrate
      any impairment of either invasion or growth of P. falciparum in affected red
      cells under physiological conditions.

PMID- 15462918
TI  - Flying squirrels and their ectoparasites: disseminators of epidemic typhus.
AB  - Information gathered during the past decade indicates that the eastern flying
      squirrel, Glaucomys volans, is a zoonotic reservoir of Rickettsia prowazekii -
      causative agent of louse-borne (epidemic) typhus. The sporadic cases o f typhus
      that have occurred in the USA in association with flying squirrels provide
      evidence that flying squirrels can transmit R. prowazekii infection to humons.
      Strains of R. prowazekii, isolated from flying squirrels multiply readily in
      human body lice, but flying squirrel lice, although readily infected, are very
      host specific and tend not to bite humans. It may be that the infection is spread
      to humans in infective ectoporasite faeces aerosolized when the flying squirrels
      groom themselves. As Joseph McDade emphasizes in this article, current concepts
      of typhus epidemiology and control must be re-evaluated to take into account this
      zoonotic aspect.

PMID- 15462919
TI  - Host specificity of trichodinid ectoparasites of freshwater fish.
AB  - Ciliophorons of the family Trichodinidoe comprise seven genera, all of which are
      commensolists or parasites - mainly on aquatic hosts such as other ciliophorans,
      coelenterates, planctonic crustaceans, molluscs, echinoderms, amphibians and
      fish. Although the first species of this family, Trichodina pediculus, was
      described from material collected from Hydra, most literature concerns the
      trichodinids of fish-particularly cultured freshwater fish. These ciliophorans
      have been implicated in severe disease and mortalities of fish, causing severe
      economic losses in various parts o f the world. In spite o f the confused
      taxonomy o f the Trichodinidae, it now appears that they fall into four distinct
      groups representing a line of specialization towards a more exclusive niche on
      the host fish. The more opportunistic species, with a broad host range, tend to
      be larger skin parasites, while the more specialized are smaller and usually only
      parasitize the gills o f their specific host.

PMID- 15462920
TI  - Choice of sample size in parasitological experiments.
AB  - One of the most awkward practical problems confronting a research worker setting
      up an experiment is to decide how big the experiment should be. The larger the
      number of subjects then the smaller is the degree of uncertainty in the
      conclusions; but large trials are costly and may have to be of long duration, so
      there is every incentive to keep trials as small as possible. Statistics is the
      science of coping; with uncertainty, and in this article Michael Healy explains
      the statistical basis that helps to decide how big a sample size should be - how
      to balance minimum error rates with optimal cost efficiency.

PMID- 15462922
TI  - Crude oil and parasites of fish.

PMID- 15462921
TI  - Low-cost sanitation technology for the control of intestinal helminths.

PMID- 15462923
TI  - Whatever became of Isospora bigemina?

PMID- 15462924
TI  - The Toxoplasma tangle.

PMID- 15462925
TI  - Injection versus infection: the cellular immunology of parasitism.
AB  - Parasites are immunogenic. But the variety of immune responses they can elicit is
      matched by their range of mechanisms to evade, subvert or distract these
      responses. The parasites' aim is survival and reproduction, ours is to restrict
      or eliminate them, and amplification of protective immune responses has become a
      key approach to this. But while vaccination has achieved many successes against
      the 'simpler' organisms such as viruses, the more complex protozoa and helminth
      parasites have proven much less tractable. In this article, Graham Mitchell
      discusses the differences between immune responses operated by whole parasites
      and those induced by prepared fractions.

PMID- 15462926
TI  - The pathogenesis of amoebiasis.
AB  - Amoebiasis, the infection of humans with Entamoeba histolytica, has a worldwide
      distribution; humans are the main reservoir and source of infection(1), although
      some other primates can also be infected. The motile trophozoite of E.
      histolytica (Fig. 1) lives in the lumen of the large intestine where it
      multiplies and eventually differentiates into cysts which are shed in the faeces
      and are responsible for transmission of infection. Two forms of amoebiasis are
      recognized: luminal amoebiasis where no clinical signs or symptoms are apparent,
      and invasive amoebiasis where the trophozoites invade the intestinal mucosa to
      produce dysentery or amoeboma, and can spread in blood to give extraintestinal
      lesions such as liver abscess. Isoenzyme markers for pathogenic and non
      pathogenic types of E. histolytica are well documented, but there is some debate
      (see Parasitology Today, vol. 3, 37-43) about whether the two types represent
      completely separate entities or if they can change from one type to the other
      under certain circumstances (Box 1). Nonpathogenic types produce no apparent
      symptoms; in this article Adolfo Martinez-Palomo discusses the pathology
      associated with pathogenic types.

PMID- 15462928
TI  - Laminin in chagasic autoimmunity?

PMID- 15462929
TI  - Traditional anti-malarials-Sri Lankan experience.

PMID- 15462930
TI  - Too many gene libraries?

PMID- 15462931
TI  - Summer mastitis: vector transmission or not?
AB  - Summer mastitis is on acute, suppurative infection of cattle with considerable
      importance to European agriculture. The causative bacteria are thought to be
      transmitted by the fly Hydrotaea irritans (L.) but evidence for this remains
      circumstantial. In this article, Eric Hillerton presents a working hypothesis to
      explain the transmission mechanism.

PMID- 15462932
TI  - How much Ascariasis is there in Africa?
AB  - What is the real burden of parasitic infections? How many people, for example,
      are infected with the common roundworm Ascaris lumbricoides-usually cited
      as'number one' in the 'league table' of human parasite prevalence? Extrapolations
      are often made from figures for helminth infection published in 1947 by Stoll.
      More recent estimates suggest almost unbelievable numbers of oscoriosis cases -
      about 1000 million people representing about one quarter of the world population.
      Such figures are important because they contribute to the perennial debate about:
      allocation o f scarce health resources in affected countries to infections of
      greatest public health importance. But where do such figures come from? In this
      article, David Crompton and Jim Tulley report on their appraisal of Ascaris
      prevalence data for Africa. Their figures were used to compile the geographic
      histogram on this month's cover.

PMID- 15462933
TI  - The renaissance of ascaris.

PMID- 15462935
TI  - From the diary of Puer Georgius, centurion.

PMID- 15462936
TI  - Screwworm eradication in North and Central America.
AB  - Screwworms, Cochliomyia hominivorax (Fig. 1), have been eradicated from the USA
      and now have a tenuous hold only in the Yucatan peninsula of Mexico, where
      control programmes based on massive release of sterile males have recently been
      initiated. Sterile male release operations are now underway in Guatemala and
      proposals have been made to extend the eradication procedures south to the Darien
      Gap in Panama. It is planned to extend the barrier zone to Belize and Guatemala
      later this year. This article reviews the progress and operational obstacles of
      the screwworm eradication programme.

PMID- 15462937
TI  - Genetics and trypanotolerance.
AB  - Genetic resistance to disease and its use in domestic livestock usually ranks
      last, if at all, amongst preferred disease control measures - usually preceded by
      measures such as chemotherapy, vector control and vaccination. Thus, interest in
      genetic resistance is often a reflection of dissatisfaction with other control
      strategies, and the current emphasis on trypanotolerant cattle in Africa is just
      such a case. Eighty years of tsetse fly eradication programmes have had little
      impact on tsetse distribution, although recent research with odour baited targets
      impregnated with insecticide brings hope for the future. The search for a vaccine
      has proved more arduous than anticipated and the number of drugs available for
      therapy and prophylaxis is limited. In the search for alternative solutions to
      the problem of African trypanosomiasis, attention has recently focused on genetic
      resistance - a subject normally covered by immunologists or veterinarians(3-7).
      In this article, Rosemary Dolan discusses the concept from the geneticist's
      viewpoint.

PMID- 15462938
TI  - Towards global control of cystic and alveolar hydatid diseases.
AB  - Control programmes against Echinococcus granulosus in its dog-sheep transmission
      cycle (Fig. 1) have been successful in many parts of the world'. In contrast, the
      related E. multilocularis presents a much more complex problem for control
      authorities. Unlike E. granulosus, the life cycle of E. multilocularis
      predominantly involves sylvatic hosts (e.g. rodents and foxes) (Fig. 2) and the
      control of wild life echinococcosis presents a formidable challenge to ecologists
      and epidemiologists. This review contrasts the two parasites, explaining why E.
      granulosus in its domestic dog-sheep life cycle has been so responsive to
      control, and examines the prospects for control of E. multilocularis.

PMID- 15462939
TI  - The promastigote surface protease of Leishmania.
AB  - The infective forms o f several protozoan parasites are covered with a limited
      number o f major surface proteins. In this respect, Leishmania is no exception,
      and recent investigations have demonstrated on promostigotes the presence o f a
      single surface glycoprotein. In contrast to the major surface proteins o f other
      protozoans which have no known enzymatic activities, the surface protein of
      Leishmania. is a protease which is active on living cells. In this review,
      Clement Bordier presents the current structural, functional and immunological
      information concerning this intriguing and potentially important enzyme.

PMID- 15462940
TI  - Genetic variability in endoparasitic helminths.
AB  - Biochemical genetic studies have revealed high levels o f polymorphism and
      heterozygosity in natural populations of endoporasitic helminths. With few
      exceptions, these parasitic helminths appear just as genetically variable as free
      living invertebrates. But this finding is not consistent with the idea that the
      internal environment o f the host represents a stable and homogeneous habitat
      which selects for parasite homozygosity. In this article, Steven Nadler examines
      alternative explanations drawn from the perennial 'selectionist-neutralist'
      debate-do all genes necessarily confer selective advantages or disadvantages, or
      are some effectively neutral?

PMID- 15462941
TI  - Sex attractants in nematodes.
AB  - Nematodes communicate with each other using pheromones - chemicals secreted by
      one individual that affect the behaviour of others of the same species. Chemicals
      secreted into the environment are known to influence host location, dormancy
      (dauer-larva formation), competitive interactions and mate detection; they
      benefit the nematode by reducing energy expenditure on less orientated movements.
      Of these chemicals, sex pheromones associated with mate detection and attraction
      are of particular interest as potential biological control agents. Here, Barbara
      MacKinnon discusses these developments.

PMID- 15462942
TI  - Zymodemes of Entamoeba histolytica.

PMID- 15462943
TI  - Micromotility meter: instrumentation to analyse Helminth motility.

PMID- 15462945
TI  - Human migration and the spread of malaria in Brazil.

PMID- 15462944
TI  - Financial and economic aspects of environmental management for vector control.
AB  - Short term economic benefits of resource development generally carry more weight
      in political decision-making than the adverse health effects such projects may
      have in the medium and long term. This problem is particularly acute in the case
      of water resource development projects which can often promote the prevalence and
      incidence of certain vector-borne diseases such as schistosomiasis and malaria.
      And while the agricultural sector is usually strengthened by production increase
      resulting from water resource development, the health sector may ultimately have
      to pick up the bill for disease control programmes which become necessary as a
      consequence. At its sixth meeting in Geneva, the WHO/FAO/UNEP Panel of Experts on
      Environmental Management for Vector Control (PEEM) discussed the financial and
      economic aspects of environmental management, and its cost effectiveness as a
      vector control measure. Their report is now available and in this article, Robert
      Bos and Anne Mills discuss some of the key findings.

PMID- 15462946
TI  - Epidemiology and health education in Argentina.

PMID- 15462947
TI  - Wellcome malaria exhibition.

PMID- 15462948
TI  - Arrested larval development in cattle nematodes.
AB  - Most economically important cattle nematodes are able to arrest their larval
      development within the host - entering a period of dormancy or hypobiosis.
      Arrested larvae have a low death rate, and large numbers can accumulate in
      infected cattle during the grazing season. Because of this, outbreaks of disease
      caused by such nematodes can occur at times when recent infection with the
      parasites could not have occurred, for example during winter in temperature
      northern climates when cattle are normally housed. The capacity to arrest is a
      heritable trait. It is seen as an adaptation by the parasite to avoid further
      development to its free-living stages during times when the climate is unsuitable
      for free-living survival. But levels of arrestment can vary markedly in different
      regions, in different cattle, and under different management regimes. Climatic
      factors, previous conditioning, host immune status, and farm management all seem
      to affect arrestment levels. In this article, James Armour and Mary Duncan review
      the biological basis of the phenomenon, and discuss the apparently conflicting
      views on how it is controlled.

PMID- 15462950
TI  - Trypanosome culture.

PMID- 15462949
TI  - DNA diagnosis of human leishmaniasis.
AB  - Early identification of the causal agent of human leishmaniasis is difficult even
      in a well-equipped hospital. This makes early treatment of cases more difficult,
      and also adds to the problem of accurately assessing the prevalence and incidence
      of the disease. Incrimination of vector species of sandfies and reservoir hosts
      is also complicated by difficulties in detecting and identifying the infective
      organisms. Although the importance of leishmantasis is now well-recognized,
      improved methods of diagnosis have been much in demand (Box 1). In this article.
      Douglas Barker reviews progress in developing diagnostic DNA probes for the
      parasites, that are suitable for use even in field areas.

PMID- 15462952
TI  - Infective stages of free-living amoebae.

PMID- 15462953
TI  - Immune response of fish to parasitic protozoa.
AB  - Epizootic outbreaks of fish diseases are increasingly common as a result of
      intensive aquaculture, fish farming and sea ranching. Very few drugs are
      available for treatment or prophylaxis against fish diseases, and development of
      such compounds is inhibited by different national regulations governing the use
      of chemicals in fish for human or animal consumption. Alternative approaches are
      urgently needed. But although the taxonomy and biology of fish parasites have
      been extensively studied, relatively little is known about protective immunity in
      fish and the effects of parasites on the piscine immune system. In this article,
      Patrick Woo discusses the immune responses of fish to parasitic protozoa, showing
      that vaccination is a viable control strategy, and stressing the need for a
      coordinated global research programme on fish diseases.

PMID- 15462954
TI  - Trypanosoma cruzi populations: more clonal than sexual.
AB  - The ancient question of trypanosome sexuality has recently been reactivated in
      view of important observations in the African species Trypanosoma brucie, in
      which Mendelian sexuality has been proposed as a working hypothesis on the basis
      o f indirect isozyme evidence. Subsequent experiments have confirmed that
      recombination can occur in T. brucei under defined experimental conditions and
      suggest that this parasite undergoes meiosis. In this article, Michel Tibayrenc
      and Francisco Ayala discuss the intraspecific variability of another species,
      Tyapanosoma cruzi - causative agent of american trypanosomiasis or Chagas
      disease. They interpret the variation revealed by extensive isozyme analysis and
      restriction endonuclease analysis of kinetoplast DNA, to suggest that T. cruzi is
      diploid, genetically very polymorphic, and has a clonal structure that manifests
      a lack of (or very restricted) sexuality.

PMID- 15462955
TI  - Malaria: an intra-erythrocytic neoplasm?
AB  - Drug resistance is a serious problem in malaria, and prospects for new drugs are
      not optimistic. In 1963, the US Army began a huge programme to develop new
      antimalarials; they screened over 235 000 compounds, but very few were
      sufficiently active and safe for use in humans. Part of the problem is that not
      enough is known about the biochemical properties of malaria parasites, especially
      the metabolic differences between them and their host cells which could offer
      targets for specific chemotherapy. An important characteristic of malaria
      infection is the rapid growth of the parasite population, and changes in host
      metabolism that result from this. A similar effect occurs in many cancers. In
      this article, Ya Zhang argues that malaria parasites also have metabolic
      similarities with tumour cells, and suggests that careful comparison of these two
      could provide insight for new drug development.

PMID- 15462956
TI  - Do hookworms elicit protective immunity in man?
AB  - The two main species of human hookworm, Ancylostoma duodenale and Necator
      americanus (Table 1), are together believed to infect about 900 million people -
      mainly in tropical countries where adequate sanitary facilities may be lacking.
      But interactions between the two species, and their relative contributions to
      observed age-related infection patterns and seasonal cycles of transmission,
      continue to engender controversy. People tend to remain susceptible to infection
      through-out life, even with constant exposure to the infective stages. So what
      role does human immunity or resistance play in the epidemiology and control of
      infection? In this article, Jerzy Behnke reviews the epidemiology of hookworm
      infection in the light of current understanding of mechanisms involved in host
      responses to infection and hookworm evasion of those responses. As he stresses,
      much further work is required.

PMID- 15462957
TI  - Asymptomatic malaria infections--do they matter?

PMID- 15462958
TI  - Antibacterial action of Myiasis-causing flies.
AB  - Some species of calliphorid blowflies lay their eggs in wounds; their larvae
      develop by feeding on the tissue, and the infection is known as myiasis or fly
      strike. But wounds, from whatever cause, are frequently contaminated with
      bacteria - many o f which can spread in the bloodstream causing septicaemia
      and/or toxaemia. For example, wound contamination with Clostridium welchii -
      leading to 'gas gangrene' - was a frequent cause of death amongst battlefield
      casualties. It is from such situations that early observations were made on the
      beneficial effect of some blowfly larvae in limiting the bacterial infection of
      wounds. Indeed, some military surgeons would deliberately infest wounds with
      blowfly maggots in order to prevent bacterial complications. Now, a century or
      two later, the search for new antibiotics had led researchers back to these early
      observations, and in this article, Gory Erdmann describes progress in
      understanding the antibacterial action of blowfly maggots.

PMID- 15462959
TI  - Pathology of malaria-infected mosquitoes.
AB  - Concepts of the basic case reproduction rate of malaria, or the vectorial
      capacity of malaria vectors, tend to assume that the behaviour of infected and
      non-infected mosquitoes will be similar. However, recent years have seen a series
      of studies demonstrating that mosquitoes infected with malaria or other parasites
      show many pathological features with important effects on their behaviour and on
      the transmission dynamics of the parasite. Parasitology Today will be featuring a
      series of reports discussing these effects and attempting to unravel the expected
      effects on parasite transmission dynamics; this article sets the scene.

PMID- 15462960
TI  - VIIIth Ecdysone Workshop.

PMID- 15462961
TI  - CTAB precipitation of cestode DNA.
AB  - DNA probes are proving extremely valuable in the characterization o f cestodes -
      as well as other parasites. In this article, Kok Wei Yap and Andrew Thompson
      discuss some of the problems of DNA isolation, stressing the need for a gentle
      and economical procedure such as CTAB precipitation.

PMID- 15462962
TI  - Community-based malaria control in India.
AB  - India launched its National Malaria Eradication Programme (NMEP) in 1958,
      designed to interrupt transmission with residual insecticide spraying coupled
      with chemotherapy and anti-larval methods in urban areas. The strategy produced
      spectacular results. By 1965 malaria was reduced from around 75 million cases
      annually (with 800 000 deaths) to about 100 000 cases per year. Unfortunately,
      even under the subsequent maintenance phase, malaria began to resurge in many
      foci, and in 1976 the NMEP reported 6.4 million parasite positive cases. In this
      article, V.P. Sharma looks at some of the problems faced by the NMEP strategy,
      and discusses the alternative community-based approach now being evaluated in the
      northwestern state of Gujarat.

PMID- 15462963
TI  - External debt limits health interventions.

PMID- 15462964
TI  - Sporozoite rate and malaria prevalence.

PMID- 15462965
TI  - Control of malaria and filariasis vectors in South India.
AB  - Community participation is increasingly seen as a major component of successful
      control programmes against parasitic diseases. One of the strongest exponents of
      this has been the Vector Control Research Centre (VCRC) in Pondicherry, South
      India (Fig. 1), who have successfully motivated and involved village communities
      in vector control activities with considerable success against malaria and
      filariasis vectors. Their largest single programme, the Filariasis Control
      Demonstration Project in Pondicherry Town, has now been handed to the Pondicherry
      State Government, while the VCRC's work on malaria and filariasis control is now
      expanding throughout other parts of India. As this article shows, much has been
      learnt from these projects, not just about control techniques but also about
      education, administration and decision-making.

PMID- 15462966
TI  - Spread of chloroquine resistance in Plasmodium falciparum.
AB  - Malaria resistant to chloroquine has now been confirmed in more than 40
      countries. The drug was introduced in 1934, but was not in large-scale use until
      the early 1950s. Anecdotal reports suggest that resistance emerged as early as
      1957 both in Colombia and along the then Cambodia-Thailand border area. But by
      1960, resistance in these areas was confirmed - and may represent two separate
      events. Resistance spread rapidly, with a new focus of resistance confirmed in
      East Africa by 1977. Chloroquine resistance represents a severe problem both for
      prophylaxis and treatment of malaria. In this aricle, David Payne traces the
      spread of resistance and discusses some of its implications.

PMID- 15462967
TI  - Hookworm antigens: the potential for vaccination.
AB  - Hookworms rank with Ascaris as the most prevalent soil-transmitted helminths of
      man. Up to 1000 million people may be infected. Not all suffer the life
      threatening anaemia that reflects heavy burdens of hookworms, but even mild iron
      deficiency anaemia due to hookworms can lead to intellectual and growth
      retardation - especially among infected children. Health education, mass
      chemotherapy and the sanitary disposal of faeces have been the traditional
      mainstays of hookworm control, but more recently chemotherapy targeted only to
      heavily infected individuals who appear predisposed to hookworm anaemia has
      emerged as a realistic alternative. Ultimately, however, knowledge of the
      molecular immunology of hookworm infection may provide the basis for rational
      vaccine development. Although the evidence for acquired immunity to hookworms in
      man is not strong, work is now underway to identify and to characterize antigens
      from third and fourth larval stages and adults of Necator americanus and species
      of Ancylostoma (Table 1). As this article shows, the work provides real promise
      for improved immunodiagnosis and possible vaccination.

PMID- 15462968
TI  - Beyond the oocyst: Over the molehills and mountains of coccidialand.

PMID- 15462971
TI  - Art and nature.

PMID- 15462970
TI  - Clark foundation policy.

PMID- 15462972
TI  - Falciparum nomenclature.

PMID- 15462974
TI  - Genetic resistance to haemonchosis in sheep.
AB  - Parasitic nematodes cause huge economic losses to the domestic livestock
      industry. Control requires skilled farm management and heavy use of
      anthelmintics, but breeding for resistant animals has long been held a
      possibility. For about 20 years after World War ll, the genetics of association
      between sheep breeds and Haemonchus contortus - the main parasite of importance
      in sheep - was studied in the USA and Europe. Since the early 1970s, however,
      such studies have received greater emphasis in Australia, where anthelmintic
      resistance has become widespread. In this article, Douglas Gray discusses the
      background to breeding programmes for resistance to hoemonchosis - paying homage
      to the 'Golden Ram', a Merino believed to have carried a single major gene for
      immunological resistance to Haemonchus and Trichostrongylus.

PMID- 15462975
TI  - Reversal of chloroquine resistance in falciparum malaria.
AB  - Control of falciparum malaria infections has been increasingly hampered by the
      emergence of parasites resistant to chloroquine, pyrimethomine and other standard
      anti-malarials. Chloroquine-resistant strains of Plasmodium falciparum, for
      example, which originally appeared in South-East Asia and South America are now
      found in East Asia and sub-Saharan Africa(1). Attempts to combat this alarming
      development have to date taken two main forms: (1) the judicious use of existing
      ontimalarials, preferably in combinations, in an attempt to delay the emergence
      of resistance; and (2) on aggressive research effort aimed at identifying a new
      generation of antimalarial drugs. But what i f it became possible to administer
      an antimalarial drug together with a second drug capable of overcoming resistance
      to the first? A recent report from Samuel Martin and co-workers at The Walter
      Reed Army Institute of Research in Washington DC raises just such an intriguing
      possibility.

PMID- 15462976
TI  - TDR finances improve--but not yet smooth.

PMID- 15462977
TI  - Outbreak of hydatid disease in Western Australia.

PMID- 15462978
TI  - Molecular mimicry revisited.
AB  - The host immune response is an important line of defence against parasites.
      Tactics to evade this response are therefore expected in host-parasite
      relationships, and the clearest example is the antigenic variation displayed by
      African trypanosomes. But while few other parasites seem to have quite this
      ability, many seem to display a form of antigenic convergence with the host -
      allowing them a degree of molecular camouflage against the host's immune system.
      Ideas about such antigenic convergence were developed some 30 years ago, with,
      for example, John Sprent's theory of 'adaptation tolerance', John Dineen's
      'selection for fitness antigens' and Raymond Damian's concept of 'antigen
      sharing' between host and parasite which was subsequently formulated in a now
      classical exposition on 'molecular mimicry'. Damian's theory, that one of the
      mechanisms by which parasites could avoid the host immune response was by
      mimicking host molecules, has greatly influenced both the theoretical and
      practical approaches to immunoparasitology. Earlier this year, at a UCLA
      Symposium, Professor Damian discussed how the theory had progressed since its
      original exposition. This article is based on that presentation.

PMID- 15462979
TI  - Microsporidia of mammals--widespread pathogens or opportunistic curiosities?
AB  - The microsporidia are primitive eukaryotic parasites - well known in some
      invertebrates and in fish, and increasingly recognized in mammals. One species,
      Encephalitozoon cuniculi is widespread in rodents, lagomorphs and carnivores and
      has been reported in human and non-human primates. But although clinical
      expressions of E. cuniculi infections are well substantiated in carnivores,
      evidence for its pathogeniciry in primates is less clear. Indeed, serological
      evidence suggests that latent infections may be quite common in man. Another
      species, Enterocytozoon bieneusi has now been reported several times from AIDS
      patients, associated with a severe, intractable diarrhoea. Other records of
      microsporidia in mammals have also been associated with an immunoprivileged site
      or immunocompromized host. In this article Elizabeth Canning and Wafaa Hollister
      discuss the recent findings, and consider the likelihood that microsporidial
      infections of man will be increasingly revealed following immunosuppressive
      therapy. But will they be opportunistic infections, or manifestations of common
      parasites that are otherwise held at sub-patent levels?

PMID- 15462980
TI  - False parasites in tissue sections.

PMID- 15462981
TI  - Effects of host grooming on louse populations.
AB  - Grooming behaviour by the host is increasingly recognized as an important
      determinant of feeding behaviour by blood-sucking arthropods. In general,
      grooming activity increases as a function of attack rate which, in some cases,
      provides a density-dependent limitation on the success of blood feeding. In turn
      this can lead to density dependence in population parameters of the arthropod,
      and can affect transmission of some arthropod-borne parasites in a similar way.
      But although insect-host interactions at this level are now being revealed in a
      variety of blood-sucking groups, such as mosquitoes, tsetse flies and triatomine
      bugs (see Box I), they are perhaps most clearly seen in, populations of
      ectoporositic insects such as lice, which ore permanently subject to defensive
      grooming behaviour by their hosts. As Durno Murray discusses here, host grooming
      has been a dominant factor in the evolution of lice, not only at the
      morphological level but also in terms of reproductive strategy.

PMID- 15462983
TI  - The tapeworm trap and other esoteric remedies for intestinal helminths.

PMID- 15462982
TI  - Eicosanoids as immunomodulators of penetration by Schistosome cercariae.
AB  - To infect a definitive host, schistosome cercorioe must identify and penetrate
      intact skin. This involves complex biochemical and morphological changes over a
      fairly brief time (48 hours), and possibly offers a potential point of
      intervention against infection. Attempts to define a vaccine against the invading
      organisms have so far been unsuccessful, but unravelling the complex biochemical
      interactions of schistosome penetration and transformation seems to suggest
      possible pharmacological or immunopharmacological interventions against these
      initial stages of infection.

PMID- 15462984
TI  - Shakespearian parody.

PMID- 15462985
TI  - Song of hyalomma.

PMID- 15462986
TI  - Fluorescent probes for detection of protozoan parasites.
AB  - Fluorescent probes generally provide a rapid and simple staining technique,
      valuable for the rapid diagnosis of protozoal infections. However, many of these
      staining techniques have disadvantages for clinical tests: (I) they require a
      fluorescence microscope which is not always available in clinical laboratories;
      (2) the preparations are not permanent because the fluorescent probes do not
      withstand dehydration; (3) variable quenching of the fluorescence may occur,
      unless proper preventive measures are taken. In this article, Fumihiko Kawamoto
      and Nobuo Kumodo explain some of the most widely used fluorescent probes, and
      discuss how problems in their use can be minimised.

PMID- 15462987
TI  - The impact of small dams on parasitic diseases in Cameroon.
AB  - Economic development in Africa implies the provision of vast, sparsely populated
      regions with improved road networks and agricultural techniques. Climatic
      constraints mean that control of water resources is essential in arid areas. But
      hydrogrophic modifications also have the potential for adverse impact on the
      health of local populations. The extension of water sources and their all year
      round supply of water mean that people are attracted towards them, and to the
      same places where conditions favour the spread of intermediate hosts and vectors
      of parasitic diseases such as schistosomiasis, onchocerciasis, drocunculiasis and
      malaria. Doctor, epidemiologists, and the engineers involved in rural earth-works
      must therefore work together to establish systems that impede the transmission of
      such diseases. Examples from the Cameroon typify the need for such an approach.

PMID- 15462988
TI  - Do birds use biological control against nest parasites?

PMID- 15462989
TI  - Altered drug metabolism in parasitic diseases.
AB  - While the immune system represents the main line of host defence against parasite
      infections, mixed function oxidase (MFO) systems (Box 1) offer the main line of
      defence against drugs and other biologically active substances. But, as this
      review shows, many parasites can exert a profound effect on the host MFO system
      by altering the microsomal drug-metabolizing enzymes and electron transport
      carriers such as cytochrome P-450. This can markedly affect the host's ability to
      metabolize biologically active compounds, often with adverse physiological,
      pharmacological and toxicological consequences. In mammals, drug metabolism
      occurs predominantly in the liver, and to a lesser extent in the spleen, lungs,
      kidneys, intestine and cerebral tissues. Thus those parasites that occupy sites
      in these tissues - such as amoebae, Fasciola, schistosomes and malaria - tend to
      be those with greatest effects on the host's ability to metabolize drugs. The
      effects can modify the host response to substances unrelated to the infection,
      and to drugs which may be administered under a chemotherapeutic regime.

PMID- 15462990
TI  - The treatment of falciparum malaria.
AB  - Effective treatment for falciparum malaria has been available for over 300 years,
      and for most of this time physicians have argued over the best doses and the
      methods of administering antimalarial drugs. A reasonable consensus has since
      emerged on the treatment of uncomplicated malaria, but there is still
      disagreement over the management of severe infections, and as a consequence there
      have been confusing and dangerous discrepancies in treatment recommendations. In
      this review, Nicholas White discusses the confusion, offering a rational basis
      for the clinical treatment of both uncomplicated and severe falciparum malaria.

PMID- 15462991
TI  - Blastocystis hominis, a long-misunderstood intestinal parasite.
AB  - For over 50 years, Blastocystis hominis has been held to be a harmless intestinal
      yeast-probably frequent in stool samples from man and other primates, but usually
      ignored except as a possible source of confusion with Entamoeba histolytica. More
      recently, its status as a protozoan parasite has been accepted, and it is now
      increasingly recognized as an agent of intestinal disease - usually self-limiting
      but occasionally fatal in monkeys. Here, Charles Zierdt reviews the status o f
      this intriguing protozoan, drawing attention to its unusual biochemistry.

PMID- 15462992
TI  - Polyamine metabolism of filaria and allied parasites.
AB  - Putrescine and the polyamines spermidine and spermine occur both in prokaroytes
      and in eukaryotes where they seem intimately involved in regulatory processes of
      cellular growth and differentiation. They seem to play an important role related
      to the biosynthesis of nucleic acids and proteins, although at the molecular
      level their precise function remains unclear. In general, prokaryotes utilize
      putrescine and spermidine while eukaryotes tend to have higher concentrations of
      spermidine and spermine compared to putrescine(1-3.) Differences in polyamine
      metabolism between parasites and their hosts suggest several potential targets
      for chemotherapeutic attack As Rolf Walter discusses here, such approaches have
      already been exploited for African trypanosomes and also offer some leads for the
      chemotherapy of helminth infections.

PMID- 15462993
TI  - Industrial approaches to tropical diseases.

PMID- 15462994
TI  - Origin of falciparum.

PMID- 15462996
TI  - Ivermectin and faecal degradation.

PMID- 15462997
TI  - Detection of benzimidazole resistance in trichostrongylid nematodes.
AB  - Benzimidazole anthelmintics (Box 1) have an important role in the control of
      economically-important nematode parasites of sheep and other ruminants. But
      effective control and management strategies using such compounds require a clear
      appraisal of the resistance or susceptibility of the target worms. Currently
      available tests for benzimidozole resistance in trichostrongylid nematodes tend
      to be costly, time-consuming and technically-demanding - as a result, attention
      is now turning to biochemical assays.

PMID- 15462998
TI  - Estimating LD50s without a computer.
AB  - Quantitative analysis of dose-related effects, such as mosquitoes killed by
      insecticide or parasites killed by a drug, usually involves estimating the dose
      which kills, on average, 50% of the subjects. This quantity is often termed the
      LD(50) (LD for lethal dose), or the ED(50) (ED for effective dose). Other
      specified response levels, such as the LD(90) - the dose that kills 90% of
      subjects - may also be derived. Dose-related effects of this type follow an S
      shaped curve because, clearly, doses lower than those giving zero response will
      also give zero response, while at the other end of the curve, doses above those
      giving a maximum response can also only give a maximum response. In other words
      the curve flattens out at both ends. The mathematics of fitting a suitable S
      shaped curve to such data - for example by probit analysis - is quite simple in
      principle but can be arduous and time-consuming without a suitably programmed
      computer. In this article, Michael Healy explains an alternative approach which
      is particularly applicable to field observations where computers are unavailable.

PMID- 15462999
TI  - Bednets revisited- old idea, new angle.
AB  - Bednets, especially nets impregnated with repellant or insecticide, are
      attracting increasing interest as a key intervention against mosquito-borne
      parasites. They are relatively cheap and simple to use, and if arranged correctly
      can give protection against mosquitoes and other nocturnal biting flies. Such
      ideas however, are far from new, and in this essay, Steve Lindsay and Mary Gibson
      review some historical highlights of bednet development.

PMID- 15463000
TI  - Pathophysiology of toxoplasmosis.
AB  - Toxoplasma infection in most adult animals and humans is asymptomatic because of
      effective protective immunity; this involves antibody acting extracellularly, and
      T-cell factors acting intracellularly. Whenever immunity is not acquired in a
      timely fashion, tachyzoites continue to multiply, destroying an excessive number
      of cells, producing lesions in several organs, with pneumonia and encephalitis
      the prominent causes of illness and death. However, immunity is insufficient to
      destroy the slowly multiplying bradyzoites persisting in tissue cysts in many
      organs - a parasite adaptation to await ingestion of one host by another.
      Toxoplasma cysts produce lesions when they disintegrate, because of the delayed
      type of hypersensitivity accompanying infections. In the presence of immunity,
      the released bradyzoites are destroyed, but when protective immunity fails, the
      bradyzoites can develop again into actively multiplying tachyzoites parasitizing
      and destroying cells in expanding foci, usually in the brain. In this review J.K.
      Frenkel discusses the complex interplay of immunological and parasite factors
      participating in the various lesions associated with acute and chronic Toxoplasma
      infections.

PMID- 15463001
TI  - Loa loa - a neglected filaria.
AB  - There has been considerable research on the biochemistry and immunology of many
      human, veterinary and laboratory animal filariae, with a view to understanding
      pathogenic and protective immune mechanisms and developing ways to boost them(1
      3). But, apart from a few isolated reports (eg. Refs 4,5), these aspects have
      been largely ignored for the human filarial parasite Loa loa. Obviously not all
      filariae can be studied in equal depth - almost 100 different life cycle patterns
      are documented(6) - but, as Margaret Pinder shows here, L. loa is an important
      human pathogen of considerable biological interest.

PMID- 15463002
TI  - Parasitic diarrhoeas in China.
AB  - Parasitic diseases associated with diarrhoea are increasingly recognized as
      important public health problems in China. They range from well-known intestinal
      infections such as giardiasis, to infections better known for other symptoms -
      such as malignant malaria and schistosomiosis. In this review, Dr Wang Cheng-i
      discusses recent Chinese studies on giardiasis and amoebiasis, which have been
      somewhat neglected in the past, and on cryptosporidiosis and infantile hookworm
      infection which have only recently been recognized as a health problem in China.

PMID- 15463004
TI  - Chloroquine vs malaria.

PMID- 15463003
TI  - Viruses of parasitic protozoa.
AB  - Associations are increasingly recognized between parasitic protozoa and smaller
      organisms such as bacteria (see Parasitology Today 1, 143), and viruses. Their
      revelation, originally by ultrastructural studies, may now be indicated by
      observations of 'rogue bands' on gel electrophoresis of parasite nucleic acids.
      The origins and roles of parasite 'parasites' are still uncertain, but, as
      Michael Miles suggests here, they may prove of particular importance as agents to
      introduce genes for important immunogens into non-pathogenic protozoa for vaccine
      delivery.

PMID- 15463005
TI  - Dinner sans pyrethroid.

PMID- 15463006
TI  - Reply.

PMID- 15463007
TI  - Density-dependence in parasite transmission dynamics.

PMID- 15463008
TI  - Diagnostic DNA amplification no respite for the elusive parasite.
AB  - In the [Formula: see text] years since its addition to the 'molecular biology bag
      of tricks', in vitro DNA amplification by the polymerase chain reaction has made
      a considerable impact on medical research. A breakthrough into the field of
      molecular parasitology is now imminent - especially through the use of
      thermostoble DNA polymerise. In this introduction Maarten de Brujin discusses the
      general principles of the method together with recent technical improvements,
      suggesting some potential applications for diagnosis of parasitic diseases and
      some of the pitfalls that may be anticipated.

PMID- 15463010
TI  - So long- and thanks for all the ticks.

PMID- 15463009
TI  - Saint Lucia revisited.
AB  - The eastern Caribbean island of Saint Lucia is now famous in parasitological
      history as the setting for a major programme of schistosomiasis control'. Perhaps
      less well-known are the island's effective control of many intestinal parasites,
      and elimination of malaria, such that the current patterns of mortality and other
      demographic indicators now resemble those of industrialized countries. More
      recently, the island has become the focus for another community-based health
      programme as the Caribbean region again comes to grips with Aedes aegypti and its
      recently imported relative, Aedes albopictus, important vectors of yellow fever
      and dengue viruses (see Box 1).

PMID- 15463011
TI  - Trichuris is not trivial.
AB  - There is no doubt that whipworm, Trichuris trichiura, is common - infecting up to
      800 million people throughout tropical and temperate areas. Less clear has been
      its clinical significance, largely because of the chronic insidious nature of the
      disease. Here, Ed Cooper and Don Bundy discuss the scale of disease caused by
      Trichuris, pointing to possible reasons for its neglect- under-recognition, under
      reporting, and/or uncertainty of pathogenesis.

PMID- 15463012
TI  - Parasite heat-shock proteins.
AB  - Many parasites, including most of those of medical or veterinary importance,
      experience a major increase in ambient temperature at some stage during their
      life cycle. This occurs when a cyst or free-living larval form is ingested by a
      warm-blooded host, when a poikilotherm-infecting parasite is transmitted to a
      homeotherm, or when a transiently free-living invasive larva penetrates the skin
      of a mammal. This sudden change in temperature could be expected to stress the
      intruder, as it should dramatically alter rates of metabolic reactions and of
      denaturation of proteins. This would especially affect the function of near
      equilibrium, regulatory, and membrane-bound enzymes (changes in temperature
      affect membrane fluidity). In this article George Newport, Janice Culpepper and
      Nina Agabian consider how parasites cope with this problem, emphasizing the
      possible role of heat-shock proteins (HSPs), how the expression of these
      molecules is regulate, and how HSPs interact with the host immune system.

PMID- 15463013
TI  - Clinical use of praziquantel in China.
AB  - Praziquantel, a broad-spectrum anthelmintic developed by E. Merck and Bayer AG in
      Germany in the early 1970s, was synthesized in the People's Republic of China in
      1977 and given the Chinese name Pyquiton. After a series of pharmacological and
      toxicological studies in China, praziquantel was released for clinical use in
      1978. The drug is now available for treatment of human schistosome and other
      trematode infections as well as the treatment of cestode infections including
      cysticercosis. However, much of the clinical work has been published in Chinese
      journals that may not be universally familiar. This article summarizes some of
      the key aspects of these reports, dealing with the clinical use of praziquantel
      against schistosomiasis japonica and other helminth infections in China.

PMID- 15463014
TI  - Cell motility of sporozoan protozoa.
AB  - Parasitic protozoa need to be capable of movement. This is particularly important
      for their ability to locate and invade target cells or the organs of their hosts,
      and could therefore represent a novel target for chemotherapy or immune-mediated
      attack. Unlike the crawling movement of amoebae and vertebrate fibroblasts,
      sporozoon protozoa are characterized by a 'gliding movement' in which no obvious
      changes occur in cell shape. Here Conrad King discusses cellular motility
      particularly in sporozoites of Eimeria and Plasmodium, discussing current ideas
      about the possible motor mechanisms involved.

PMID- 15463015
TI  - Differential infectivity of Plasmodium for mosquitoes.
AB  - The four human malarias - Plasmodium falciparum, P. vivax, P. ovale and P.
      malariaecan - canonly be transmitted by mosquitoes of the genus Anopheles,
      although not all species (nor all strains) of these mosquitoes are equally
      susceptible. Moreover, there are many other plasmodial parasites of other mammals
      and birds, that can infect other genera of mosquito. What determines this level
      of vector-parasite specificity? Malarial gametocytes, ingested by a feeding
      mosquito, must transform to gametes, fuse to form zygotes, and then, as
      ookinetes, migrate to the mosquito's midgut epithelium to develop as oocysts that
      release sporozoites to infect the mosquito's salivary glands. During this
      process, the blood- fed mosquito is developing its peritrophic membrane lining
      the gut. In this article, the Guthors examine these parallel processes in three
      sets of mosquito-parasite models, suggesting that parasite-vector specificity may
      depend on a balance between speed of parasite development versus speed of
      formation of the peritrophic membrane which can act as a barrier to ookinete
      migration and establishment in the midgut epithelium.

PMID- 15463016
TI  - Malaria-specific T-cell clones from non-immune donors.

PMID- 15463017
TI  - High-latitude Toxocara.

PMID- 15463019
TI  - Zoonotic Giardia - the debate goes on.

PMID- 15463020
TI  - Elaeophoriasis literature needed.

PMID- 15463022
TI  - Online searching of parasitology literature.
AB  - To keep abreast of the expanding literature on parasitology is virtually a such
      full-time pursuit of source literature becomes impossible with other commitments,
      encouraging recourse to secondary sources such as abstracting journals, Current
      Contents, and even Parasitology Today. Another approach - increasingly used since
      its faltering introduction in the 1970s- involves online searching of
      computerized databases. Here, John Eyers and Angela Taylor review the application
      of such systems to parasitology.

PMID- 15463023
TI  - The effect of Azolla on mosquito breeding.
AB  - Surface agents to smother mosquito breeding sites have been used extensively for
      mosquito larval control. Such agents range from oil films and chemical
      monolayers, to expanded polystyrene beads(1,2). Here, Lu Bao-lin discusses the
      use of Azolla - a floating fern - for a similar effect. The fern has the
      additional advantage of providing a useful source of green manure as a crop
      fertilizer.

PMID- 15463024
TI  - Onchocerciasis control programme-The human perspective.
AB  - The West African Onchocerciasis Control Programme (OCP), launched in 1974, seeks
      to interrupt transmission o f Onchocerca volvulus (Fig. I) over a vast area now
      encompassing 11 countries. The main strategy has been vector control using
      larvicides (particularly temephos) against blockfly larvae in fast-flowing rivers
      and streams. More recently, the programme has also begun to implement large-scale
      chemotherapy using ivermectin. The OCP has an operational budget approaching
      US$25 million a year. The control activities have led to a dramatic decrease in
      the incidence of new cases, while overall prevalence of infection has been
      reduced from about 25-30% to below 5%, accomponied by a similar drop in the
      numbers o f people presenting severe ocular involvement or blindness.
      Entomological, clinical and epidemiological results of the programme have been
      discussed in detail -particularly in the various reports produced by programme
      personnel and associated researchers (eg. Ref. I). Here, we asked James Senghor
      and Ebrohim Samba to discuss what the programme has meant to the people involved.

PMID- 15463025
TI  - Schistosome proteases.
AB  - While studies of schistosome antigens have proceeded rapidly over the past ten
      years, studies of schistosome enzymes have also been increasing apace. Now the
      two 'lines' of research are coming together. Parasites such as schistosomes
      hardly present antigens merely to stimulate a host immune response, so it is not
      surprising that many antigens turn out to have functions, for example, as
      enzymes. One type of antigenic schistosome enzyme - glutathione S-transferase -
      already shows promise as a vaccine candidate. Here, Jim McKerrow and Mike
      Doenhoff review another important class of enzyme, many of which are clearly
      antigenic, the schistosome proteases.

PMID- 15463026
TI  - Oxidative killing of intracellular parasites mediated by macrophages.
AB  - An important function of macrophages is to eliminate invading pathogens, and one
      of their main weapons involves the generation of lethal oxygen radicals. Yet some
      parasites and pathogens - notably Leishmania, Toxoplasma, and Listeria and
      Mycobacterium - make use of macrophages as their primary cellular hosts
      displaying a capacity to survive the oxidative killing mechanisms of these host
      cells. It is now clear that more than one pathway is involved in the activation
      of macrophages to kill intracellular pathogens. Here, Huw Hughes discusses the
      biochemistry of the oxidative metabolism of macrophages, and the steps taken by
      parasites to survive within this hostile environment.

PMID- 15463027
TI  - Chagas disease in Mexico.
AB  - Mexico - the northernmost country of Latin America - has long been thought to
      have an unusually low prevalence of Chagas disease compared with other Latin
      American countries. This has seemed unusual because of the large number of vector
      species and subspecies reported from the country, and the social and ecological
      conditions that seem to parallel those in other countries where Chagas disease is
      recognized as a major public health priority. This review seeks to clarify the
      question, and suggests that the epidemiological, parasitological, and
      entomological pattern of Chagas disease in Mexico may also parallel that of other
      endemic regions, but has been masked by poor awareness of the disease both at
      local and institutional levels.

PMID- 15463028
TI  - How do African game animals control trypanosome infections?
AB  - African trypanosomiasis is endemic over much of sub-saharan Africa. But whereas
      domestic animals - especially cattle - often succumb to the infection, wild
      mammals generally show a high degree o f resistance. Many species o f wildlife
      living in tsetse-infested areas carry trypanosome infections, and so act as
      important reservoir hosts, but generally show no obvious ill-effects. How they
      survive the infection is an important question in understanding mechanisms o f
      trypanotolerance, yet relevant data are sparse and scattered. Here, Ayub Mulla
      and Roy Rickman review some of the previous studies to illustrate how complex the
      question is.

PMID- 15463029
TI  - Immune suppressor substance in experimental chagas disease.
AB  - Specific and generalized immune suppression has been reported in several acute
      and chronic parasitic infections. In Chagas disease, soluble suppressor
      substances have been demonstrated in murine experimental models, but the nature
      and origin of these substances remain uncertain. Here, Eddy Liew reviews recent
      findings on immune suppression in inbred mouse strains infected with Trypanosoma
      cruzi. He suggests that production of suppressor substances may be an appropriate
      means to balance host-protective immunity with the possible risk of autoimmune
      disease, but, because of the apparent genetic restriction of suppressor substance
      production, raises doubts about its true biological significance.

PMID- 15463030
TI  - Polyamine biosynthesis and inhibition in Trichomonas vaginalis.
AB  - Polyomines - particularly putrescine, spermidine and spermine - are ubiquitous
      components of eukaryote and most prokaryote cells, and are essential for optimal
      cell proliferation. But since routes of polyamine synthesis may differ, for
      example between parasites and their hosts, selective inhibition of polyamine
      metabolism offers an attractive target for chemotherapy - as already shown with
      the success of difluoromethylomithine (DFMO) as an inhibitor of polyamine
      synthesis in African trypanosomes. Parasitology Today has featured a series of
      articles reviewing research on polyamine metabolism of various parasites (eg.
      vol. 3, pp 190-192, pp 312-315; vol. 4, pp 18-20) and here, Nigel Yorlett
      discusses these metabolic aspects of Trichomonas vaginalis (Fig. 1)-a common
      parasite of the urogenital tract.

PMID- 15463031
TI  - Trypanosome vaccines.

PMID- 15463032
TI  - Parasites in the press.

PMID- 15463033
TI  - Control of sheep lungworm in India.
AB  - Lungworm infections (parasitic bronchitis) of sheep and goats are widely
      prevalent in hilly regions of India and neighbouring countries. Several species
      of strongyloid nematodes are involved but the most prevalent, and most
      pathogenic, is Dictyocaulus filaria - responsible for heavy mortality in young
      animals and severe morbidity in survivors. Control of these parasites now relies
      on a gamma-attenuated D. filaria vaccine developed in India in 1971. Vaccination
      of 6-week-old lambs has since become an accepted part of the regular sheep
      husbandry practice in India, and trials are now underway to extend use of the
      vaccine to goats, and to set up similar vaccination procedures in other
      countries. In this review, the authors trace the development of the D. filaria
      vaccine, highlighting its production and application. Although imperfect, the
      vaccine is now making a substantial contribution to improved sheep rearing by
      pastoral in the northern hill areas of India.

PMID- 15463034
TI  - Control of Theileria annulata in Iran.
AB  - Tropical theileriosis or Mediterranean Coast Fever - caused by Theileria annulata
      - is a disease of cattle widely distributed across southern Europe, north Africa
      and central Asia. Its distribution broadly corresponds with that of its main
      ixodid tick vectors Hyalomma excavatum and H. detritum (Fig. 1). 'Exotic' cattle
      (Bos taurus) are particularly susceptible with mortalities up to 40-80% in some
      areas, whereas indigenous cattle (B. indicus) generally suffer much lower
      mortalities (about 10%) confined mainly to calves. But because imported non
      immune cattle are so susceptible, T. annulata represents a major constraint to
      livestock improvement programmes in many parts of the middle east and Asia.
      Cattle that recover from T. annulata infection generally show a solid, long
      lasting immunity. For many years there have been programmes to protect cattle by
      inoculation with blood from sick animals, and more recently using live attenuated
      T. annulata vaccines prepared from cultured schizont-infected lymphoid cells.
      This article reviews a 14 year immunization programme against T. annulata in
      Iran.

PMID- 15463035
TI  - T-cell clones in immunoparasitology.
AB  - Cell-mediated immunity (CMI) is important in many parasitic infections.
      Stimulation by parasite-specific antigens can induce clonal expansion of parasite
      specific T-cells which may act by direct cytotoxic action or by indirect effects
      on other cells such as natural killer cells or antibody-producing B-cells (Box
      1). In many cases however, the precise effector functions and the identity of
      antigens that elicit protective responses in parasitic infections are poorly
      defined. Analysis of proliferative and cytotoxic activities of subcloned cultures
      of T-cells stimulated with parasite antigens can provide some clues about the
      importance of CMI, but, as this review shows, much more precise information can
      be obtained by analysis of the response of cloned T-cell cultures.

PMID- 15463037
TI  - III International conference on malaria and babesiosis.

PMID- 15463036
TI  - In vitro development and antigen analysis of Sarcocystis.
AB  - During the past year considerable progress has been made in developing an in
      vitro system for growing large numbers of merozoites (the disease-causing stages)
      of Sarcocystis species that infect livestock. This system provides researchers
      with a means to study mechanisms of immunity and pathogenesis; and may eventually
      be used to develop effective diagnostic tests and vaccines against these
      economically important parasites. In this article, Carl Speer and Don Burgess
      discuss their in vitro system and show how preliminary antigen analysis has
      helped to deduce a possible mechanism for the vascular damage commonly observed
      in Sarcocystis infections.

PMID- 15463038
TI  - Leishmaniasis: the first centenary (1885-1985) new strategies for control.

PMID- 15463039
TI  - Cutaneous leishmaniasis: The prospects for a killed vaccine.
AB  - Of the various protozoal diseases for which vaccines are under development,
      cutaneous leishmaniasis (CL), in spite o f its chronic nature, may provide the
      best candidate for success. Stringent experimental models are available for both
      new and old world CL, human studies have been conducted for several years, and
      there is now considerable experience in using both attenuated and killed
      vaccines. In this article, Chuck Greenblatt discusses this experience, showing
      how it has led to current WHO-TDR plans for field trials of killed vaccines
      followed by virulent challenge (as used in Iran in the practice of
      'leishmanization').

PMID- 15463040
TI  - Controlled release devices for the delivery of anthelmintics in cattle.
AB  - Control of cattle helminths is not so much a problem of drug choice, but of drug
      delivery and livestock management. Several effective anthelmintics are available
      for domestic livestock, but their efficiency in limiting infection and disease
      attributed to important parasites such as Ostertagia and Haemonchus has been
      mainly due to good management practice and strategically timed treatment based on
      detailed epizootiological studies of parasite transmission. In most situations,
      treated animals remain fully susceptible to reinfection if continually grazed on
      contaminated pastures, and this is the rationale behind techniques for continuous
      or multiple treatment with anthelmintics. In response to these treatment
      requirements, the animal health industry has developed controlled release
      devices, or boluses, that can be implanted orally into the rumen (Fig. 1) to
      release anthelmintics over an extended period - either in a delayed or pulsed
      fashion. In this article, Gary Zimmerman and Eric Hoberg discuss same of the most
      promising of such devices.

PMID- 15463041
TI  - Small dam health studies.

PMID- 15463042
TI  - To wash or not to wash (Nytrel filters and urinary Schistosomiasis).
AB  - Nytrel polyamide mesh filters can be used in filtration of urine in order to make
      quantitative counts of eggs of Shistosoma haematobium. In this article, Ken Mott
      discussed recent criticism of the WHO recommendations for reuse of these filters.

PMID- 15463043
TI  - Pyrimethamine resistance in malaria parasites.

PMID- 15463044
TI  - Evidence that giardiasis is a zoonosis.

PMID- 15463045
TI  - Giardiasis--is it really a zoonosis?

PMID- 15463046
TI  - The Anopheles culicifacies complex and control of malaria.
AB  - Of the 50 or so species and varieties of anopheline mosquito in India, about 20
      are implicated as vectors of human malaria. Of these, perhaps the most important
      and widespread is Anopheles culicifacies s.l. For the first 10 years of
      widespread DDT spraying, An. culicifacies remained susceptible to this
      insecticide - indeed, some thought it lacked resistance genes altogether. By 1960
      however, resistance to DDT was apparent. DDT is a cheap insecticide, and its use
      is still favoured for mosquito control wherever it remains effective. But by the
      end of the late 1970s it appeared that DDT resistance in An. culicifacies (and
      other species) was a major barrier to effective vector control in several areas -
      particularly in parts of the northwestern states. Yet in other areas DDT still
      seemed to be effective. There was also increasing evidence from other studies
      suggesting differences in An. culicifacies found in different areas -
      particularly differences in seasonal prevalence and man-biting activity. We now
      know - as Sarala Subbarao discusses here - that An. culicifacies s.l. represents
      a complex of at least four sibling species. But in this case, one of the most
      important findings is that DDT resistance is mainly associated with species B
      which proves to be a very poor vector of malaria. Such findings, made possible by
      careful cytogenetic studies, have very important consequences for malaria
      epidemiology and control policies.

PMID- 15463048
TI  - Regional workshop on hydatid disease.

PMID- 15463047
TI  - Topical chemotherapy of cutaneous Leishmaniasis.
AB  - Cutaneous leishmaniasis (CL) is one of the most important causes of chronic
      ulcerative skin lesions. The disease is endemic in many parts of the world,
      presenting a range of clinical forms - acute, chronic, recurrent and diffuse(1).
      Several species of Leishmania are involved, including L. major, L. tropica and L.
      aethiopica in the Old World, and several members of the L. braziliensis and L.
      mexicana complexes in the New World. Some forms of the disease produce only mild,
      self-limited lesions, while at the other extreme are the destructive
      mucocutaneous forms caused by L. braziliensis and L. panamensis(1-7). In all
      cases, chemotherapy tends to be difficult - often requiring prolonged parenteral
      administration of toxic drugs such as pentavalent antimonials or amphotericin B.
      Such drugs are also expensive and relatively inefficient in the sense that much
      of the active ingredient is excreted by the patient before reaching its target.
      Consequently, there is renewed interest in the development of active formulations
      suitable for topical application directly onto the lesions.

PMID- 15463050
TI  - Trichinosis revisited--another look at modes of transmission.

PMID- 15463049
TI  - Reducing agents and Entamoeba histolytica.
AB  - Entamoeba histolytica remains an important but enigmatic parasite. It displays
      both non-pathogenic and invasive pathogenic types, which can be distinguished
      clinically and by isoenzyme markers. Yet as debated in Parasitology Today last
      year(1), the relationship between these two forms remains unclear. Bacterial
      associates and reducing agents are known to play on important role in the culture
      of E. histolytica, and possibly in its differentiation and invasive mechanisms.
      This article briefly reviews available information on the role o f reducing
      agents, and explores the possibility that bacteria may play a role in reduction o
      f toxic oxygen product - thereby promoting the virulence of E. histolytica. The
      review is not definitive, but should help to stimulate further research in this
      neglected area.

PMID- 15463051
TI  - Taiwan taenia and taeniasis.
AB  - Toeniids are large tapeworms, common throughout the world. Two species, Taenia
      saginata and T. solium are common parasites of man. The adult worms parasitize
      the small intestine, while immature stages (metacestodes or cysticerci) develop
      mainly in cattle in the case of T. saginata or pigs in the case of T. solium.
      Cysticerci of T. saginata rarely develop in man, although humans are easily
      infected with those of T. solium after eating raw or undercooked infected pork
      producing the disease known as cysticercosis. In Taiwan, both the pork and beef
      tapeworms have been documented among aboriginal peoples - with T. saginata
      considered the most prevalent species. But, as P.C. Fan discusses here, the
      'Taiwan Taenia' has several unusual features - not least the fact that beef is
      not part of the traditional diet of Taiwan oboriginols.

PMID- 15463052
TI  - Complement mediated evolution? April reflections on parasitic protozoa.

PMID- 15463053
TI  - Novel source of parasitological information.
AB  - Seldom if ever have parasitological insights been found in the great works of
      literature. Important observations on the transmammary transmission o f hookworm,
      however, may be found in a literary manuscript recently discovered in a Parisian
      archive. The concept of transmammary transmission is now well established, and
      while canine hookworm species are generally considered incapable of reaching
      maturity in man, they may well be capable of producing transient patent
      infections in neonates. The manuscript, to judge by its literary style, is
      clearly a fragment written by Marcel Proust (1871-1922) for his great seven-part
      masterpiece A la Recherche du Temps Perdu (Remembrance of Things Past) and
      perhaps it will appear in future editions. The manuscript was discovered by
      Professor C.A.M. Bell, who has kindly provided the following translation.

PMID- 15463054
TI  - Density-dependence in parasite transmission dynamics.
AB  - The transmission of vector-borne parasites is complex, yet to a large extent this
      complexity can be unravelled through the insights gained from simple mathematical
      models of the transmission system. The principle is simple because the key
      question is merely "what is the rate of increase in numbers of hosts affected?"
      Clearly, if this rate of increase is greater than unity then the infection can
      spread, while if it is less than unity it will decline. Ronald Ross in 1911 was
      the first to formulate this idea for malarial(1) and malaria transmission has
      since attracted most attention from modellers of parasitic diseases(2-4). But
      although it is implicitly recognized that nothing- not even parasitic
      transmission - can increase indefinitely, the importance of some degree of
      density-dependence in regulating the system tends to be neglected (see Box 1). In
      this article, Klaus Dietz explores some classical ideas of modelling parasitic
      disease transmission, emphasizing not only the importance of density dependence
      but also the importance of knowing exactly where such effects operate in the
      system.

PMID- 15463056
TI  - Arrested larval development and anthelmintic resistance in cattle nematodes.

PMID- 15463055
TI  - Immune mechanisms in insects.
AB  - Understanding immune evasion by parasites in their insect vectors requires some
      understanding of the insect immune system. Until fairly recently, technical
      difficulties in handling cells and plasma hampered laboratory investigations into
      insect immunology, but modern techniques combined with a sound knowledge of
      insect physiology are now permitting rapid advances. Rather than discussing the
      many controversies, this review aims to point out current areas of research into
      cellular and 'humoral' mechanisms that might be followed up by parasitologists.

PMID- 15463057
TI  - Ribosomal RNA for sporozoite detection.

PMID- 15463058
TI  - Ivermectin and cattle dung--a case for concern.

PMID- 15463059
TI  - Helminth eggs in blood films.

PMID- 15463061
TI  - Workshop on modelling sleeping sickness epidemiology.

PMID- 15463060
TI  - Tsetse immunity and the transmission of trypanosomiasis.
AB  - Cyclical transmission of African trypanosomes - Trypanosoma congolense and
      subspecies of T. brucei - depends on their uptake by and development within their
      tsetse fly vectors. Tsetse susceptibility to such trypanosome infection seems to
      be controlled by maternally inherited rickettsia-like organisms (RLOs) (Fig. 1)
      and it now seems that the RLOs may exert this effect by controlling midgut
      lectins in the fly. Ian Maudlin and Susan Welburn explain the latest findings.

PMID- 15463062
TI  - Did medicated salt hasten the spread of chloroquine resistance in Plasmodium
      falciparum?
AB  - With acknowledged difficulties in achieving satisfactory compliance rates for the
      large-scale delivery of many antiporositic drugs, the use of medicated salt has
      often been seen as a useful way to improve the level o f treatment in target
      populations. Iodinated salt is said to have contributed to a decline in endemic
      goitre, and salt medicated with chloroquine and/or other antimalorials, or with
      diethylcarbomazine, has been widely used in public health programmes against
      malaria and filariosis respectively. In this article, however, David Payne
      suggests that chloroquinized salt programmes may have been a major factor in
      promoting chloroquine resistance in Plasmodium falciparum.

PMID- 15463063
TI  - The status of Leishmania tarentolae/Trypanosoma platydactyli.
AB  - Taxonomic studies and classification of Leishmania species have developed rapidly
      in recent years, but controversy still surrounds the relationships between those
      species infecting lizards and those infecting mammals. Some authorities maintain
      that the leishmanias o f lizards form a sufficiently distinct group to be ranked
      as a separate genus - Sauroleishmania(1,2) - while Wallbanks et al. have gone
      further to suggest that such species might be classified within the genus
      Trypanosoma(3). This suggestion followed from work showing that promostigote
      forms of Trypanosoma platydactyli from a gecko, had similar isoenzyme profiles to
      Leishmania tarentolae, a well-known species from lizards. In this article
      however, Larry Simpson and George Holz Jr discuss conflicting evidence,
      concluding from recent studies of DNA and lipid composition that the lizard
      leishmanias are more closely related to mammalian leishmanias than to
      trypanosomes.0.

PMID- 15463064
TI  - Resistant flat oysters offer hope against Bonamiasis.

PMID- 15463065
TI  - Immunology of giardiasis.
AB  - Symptoms of giardiasis vary widely - partly owing to host characteristics and
      partly, perhaps, to different 'strains' of the parasite. In parallel, the immune
      response to Giardia also varies - involving humoral and cellular components both
      in the serum and the intestinal mucosa. In this article, Neal denHollander, Doone
      Riley and Dean Befus take a critical look at accumulating information about
      Giardia immunology, and discuss how the miscellany of factors may contribute to
      the immunopathology of the disease.

PMID- 15463066
TI  - Neurocysticercosis in Mexico.
AB  - Cysticercosis is caused by the establishment of Taenia solium larvae
      (cysticerci), mainly in the central nervous system (CNS) and skeletal muscle of
      humans and pigs, after ingestion of eggs shed in human faeces by the adult
      tapeworm (see centrepage diagram). Human neurocysticercosis - often a life
      threatening disease - is increasingly recognized as a public health problem,
      especially in developing countries. Clinical incidence of neurocysticercosis can
      reach 7% in Mexico and 18% in the Ekari population of New Guinea, while
      prevalence in autopsies ranges from 0.4% to 3.6% in several countries of Latin
      America, Asia and Africa. Many cases have also been recently reported in the USA,
      usually in immigrants. In this review, Ana Flisser focuses on the problems of
      cysticercosis in Mexico, where the disease is now recognized as a priority both
      in public health and economic terms. Recognition of the problem has been greatly
      aided in recent years by new developments in diagnosis - especially computed
      tomography (CT) to diagnose early stages of neurocysticercosis - and by improved
      drug treatment.

PMID- 15463067
TI  - Trypanosoma evansi in Asia.
AB  - Trypanosoma evansi has the widest geographical range of all the pathogenic
      trypanosome species and infects domesticated livestock in many countries of South
      America, Africa and Asia. In spite of this wide distribution, T. evansi has been
      less intensively investigated than the African tsetse-transmitted trypanosomes
      and there is correspondingly less information available on the incidence and
      economic importance of the disease that it causes. Many of the new techniques in
      immunology and molecular biology, which have provided much fundamental
      information on the tsetse-transmitted trypanosomes, have yet to be applied to T.
      evansi. Interest in T. evansi is increasing and a Working Group has now been
      established to coordinate and promote future research (Box 1). T. evansi is an
      important aetiological agent of disease in the livestock of Asia; this article
      evaluates both the historical perspective and our current knowledge of the
      epidemiology and pathology of T. evansi in this region.

PMID- 15463068
TI  - AIDS to communication.

PMID- 15463069
TI  - More parasites in the press.

PMID- 15463071
TI  - The anthelmintic action of praziquantel.
AB  - Although fairly expensive (around US$4.00 per single dose) praziquantel is now
      the most favoured drug against all forms of schistosomiasis, and against many
      other helminth infections. It is now marketed by four companies: E. Merck and
      Bayer (F.R.G.), Ames-Myers (USA), and Shin-Poon Pharmaceuticals (S. Korea).
      Administration of praziquantel typically causes paralysis of susceptible worms,
      or damage to their tegument, making them more vulnerable to host enzymes or
      antibody-dependent immune effector mechanisms. Other effects may also be
      involved. Here, Bill Harnett reviews the range of anthelmintic effects displayed
      by this remarkable drug.

PMID- 15463072
TI  - Malaria outbreaks in new foci in Sri Lanka.
AB  - During its Malaria Eradication Programme (1958-1964) Sri Lanka spectacularly
      reduced its malaria incidence from around half a million per year to 17.
      Regrettably, this magnificent achievement could not be maintained, and malaria
      once again reached epidemic proportions in some areas. Of particular concern
      however, has been the emergence of new foci of malaria around the hill capital,
      Kandy, discussed here by Manel Wijesundera. The new outbreaks seem intimately
      related to hydrological changes brought about by major irrigation and
      hydroelectric schemes on the Mahaweli river. The priority for such schemes is
      not, of course, to flush out the pools where mosquito larvae thrive, but to
      divert water for irrigation and power generation. In parallel, human migration
      between malaria endemic and non-endemic areas - stimulated by the resettlement
      required by the dam reservoirs - has contributed to increased malaria
      transmission. In a sense therefore, this story is a classic of health impact
      overlooked in favour of agricultural and industrial development. But whereas most
      documented cases relate to extensive flooding causing an increase in vector
      breeding sites and so exacerbating disease transmission, this story is just the
      opposite. Here, it is reduction in water flow that has promoted an increase in
      vector breeding.

PMID- 15463073
TI  - Parasitological clerihews.

PMID- 15463074
TI  - Parasitology Today readership survey.
AB  - Our February readership survey gave interesting information, and some fairly
      universal cris de coeur - especially about the lack of funds available to support
      field research. You were critical of the journal's delivery times - which, for
      various reasons, should now improve - but in amongst the compliments and
      undisguised flattery were some real gems. I want to thank all of you who sent in
      completed replies, and here I have attempted to summarize some of the most
      significant trends suggested by your responses.

PMID- 15463075
TI  - Non-random host selection by anopheline mosquitoes.
AB  - Malaria represents a complex system. Transmission depends on a multitude of
      factors - of which vector density may not be the most important (see Box 1). The
      classical Ross-Macdonald model of malaria transmission (Box 2) reveals two
      dominant factors: the probability that a mosquito will survive long enough for
      the parasite to develop to its infective stage, and the likelihood that the
      mosquito will feed on man. An important assumption however, is that all
      individuals will be at equal risk from mosquito attack. In fact, host-vector
      contact is far from randomly distributed. In this review, Tom Burkot explains the
      biological causes of non-random host selection by anopheline vectors, and Chris
      Dye discusses some of the epidemiological implications of this selection for
      malaria transmission (Box 3).

PMID- 15463076
TI  - The prevalence of Ascariasis.
AB  - The common roundworm, Ascaris lumbricoides, is probably the most prevalent human
      intestinal helminth. Previous estimates of world prevalence range from around 650
      million to 1000 million. By a detailed literature search, David Crompton now
      confirms the upper figure - estimating a world prevalence of 1008 million
      representing about 22% of the world population. The infection is known from 153
      out of 218 recognized countries.

PMID- 15463077
TI  - Role of the RGD sequence in parasite adhesion to host cells.
AB  - For many protozoan parasites, one of the first events in the process of infection
      is attachment to the surface of host cells. This adhesion phase usually involves
      ligand-receptor interactions, and has stimulated interest in the biochemical
      characterization of those host cell and parasite surface components involved. In
      this article, Ali Ouaissi discusses the strategy employed by pathogens such as
      Trypanosoma cruzi, Trichomonas, Leishmania and Treponema pallidum, in binding to
      their host cells' fibronectin receptors. Two systems appear available - to bind
      to the dimeric cell surface fibronectin through the Arginine-Glycine-Aspartic
      acid (RGD) sequence that is not occupied by the host cell surface receptors, or
      to present a surface antigen representing a 'fibronectin-like' molecule
      containing the RGD sequence directly to the host cell fibronectin receptors.

PMID- 15463078
TI  - Pathology of bonamiasis.
AB  - Bonamiasis is a serious disease affecting the oyster industry, particularly in
      Europe where it has caused catastrophic losses since its appearance in 1979. The
      causative agent is now recognized as a protistan, Bonamia ostreae(1,2), which
      aggressively infects Ostrea species to cause clinical disease that rapidly
      spreads through oyster stocks, usually causing heavy mortalities. The economic
      importance o f this parasite has generated wide interest but, as David Bucke
      discusses here, neither its taxonomic status nor its life cycle are clearly
      understood and there is much to be learn about its pathogenesis and possible
      means of control.

PMID- 15463079
TI  - Dominant parasites of fish in Georgia, USSR.
AB  - Intensive fish breeding in artificial freshwater reservoirs and ponds is often
      accompanied by epidemics of invasive parasitic diseases. In the USSR, much
      attention is given to the study of fish parasites and diseases, revealing a range
      of protozoan and helminth parasites that can cause significant economic losses to
      the fish industry (Table I ; Refs 1-5).

PMID- 15463080
TI  - The epidemiology of Toxocara canis.
AB  - Bred as hunter, companion and pet, the dog has a long and honourable association
      with man. Yet the domestic dog can host a wide range of parasites - many of which
      can also infect humans. One of these, the ascarid nematode Toxocara canis (Fig.
      1), is of particular interest because of retinal damage that may result from
      larvae becoming trapped in the eye. At the Hospital for Tropical Diseases in
      London, about 20-30 patients with toxocariasis are treated annually. Widespread
      fouling of public parks, playgrounds and pedestrian areas with dog faeces -
      especially in large cities - is well -recognized as one of the main sources of
      Toxocara infection. Yet as Stephen Gillespie discusses here, epidemiological
      indicators vary widely and the risk of infection is often treated too lightly.

PMID- 15463081
TI  - Pyrethroid insecticides in public health.

PMID- 15463082
TI  - Mechanisms of resistance to pyrethroid insecticides.
AB  - In the 10 years or so since the photostable pyrethroid insecticides such as
      permethrin and fenvolerate were introduced, this family of compounds has become
      widely used to control agricultural pests, and finds increasing usage to control
      arthropods of medical and veterinary importance. The synthetic pyrethroids offer
      many advantages for veterinary and public health use, particularly their
      selectivity, high toxicity to insects, and relative lack of chronic effects. They
      are also inherently stable, and so have become widely used as residual sprays on
      house walls to control insects in the domestic environment. But as with other
      classes of insecticides such as organochlorines, organophosphotes and carbamates,
      resistance to pyrethroids is now increasingly reported. In this article, Tom
      Miller explains the principle mechanisms of resistance to pyrethroids, using the
      North American horn fly (Haematobia irritans) as an example now showing many
      common resistance traits.

PMID- 15463083
TI  - Current status of pyrethroid resistance in anophelines.
AB  - Similarities between DDT and pyrethroid insecticides have led to widespread
      concern that cross-resistance between them might limit the usefulness of the
      latter. Both types of insecticide have similarities in chemical structure, both
      have a negative temperature coefficient (ie. they are more active at lower
      temperatures), both act as neurotoxins on sodium channels, and both produce the
      twin effects of knockdown and kill. As discussed by Tom Miller (see pages S8-S12)
      there is firm evidence for Pyrethroid resistance in some species of medical and
      veterinary importance - especially in the horn fly, Haemotobia irritans. But in
      the case of anopheline mosquitoes, the evidence for pyrethroid resistance is much
      less strong. As Colin Malcolm explains here, a critical analysis of available
      data indicates that true physiological resistance of anophelines to pyrethroids
      is much less widespread than previous commentaries suggest. Moreover, the risk of
      cross-resistance between pyrethroids and DDT may have been over-emphasized, since
      different resistance mechanisms appear to be involved.

PMID- 15463084
TI  - Pyrethroids in the WHO pesticide evaluation scheme (WHOPES).

PMID- 15463085
TI  - Do agricultural insecticides select for insecticide resistance in mosquitoes? A
      look at the evidence.

PMID- 15463086
TI  - Insecticidal activity of pyrethroids on insects of medical importance.
AB  - Pyrethroid insecticides, from natural pyrethrins to photostable analogues,
      represent important weapons against insect pests of both economic and medical
      importance. They share many characteristics with DDT, including a negative
      temperature coefficient, and knockdown and killing activity resulting from action
      against the sodium channels of the peripheral and central nervous systems. In
      this review, Eduardo Zerba summarizes what is known about their penetration into
      target insects, their mode of action, metabolism and excretion.

PMID- 15463089
TI  - Gender-dependent patterns of infections and disease.

PMID- 15463087
TI  - New directions in tropical health for Australia.

PMID- 15463090
TI  - Vaccination with 'concealed' antigens for tick control.
AB  - Ticks are responsible for substantial economic losses to the livestock industry,
      necessitating intensive use of chemical acoricides in many parts of the world.
      Problems of chemical residues, cost of acoricides, and development of resistance
      by ticks, have long been recognized and have helped to stimulate interest in tick
      control by immunological means (see Box 1). One approach has been to seek ways to
      enhance the natural immunity often acquired by animals in response to tick
      infestation. An alternative, discussed here by Peter Willadsen and David Kemp, is
      to vaccinate with 'concealed' tick antigens not normally encountered by the host,
      and so stimulate a different immune effector mechanism.

PMID- 15463093
TI  - Waterborne Giardia and Cryptosporidium.

PMID- 15463092
TI  - Schistosomiasis in cameroon.

PMID- 15463095
TI  - Giardiasis a zoonosis in Australia?

PMID- 15463097
TI  - Mechanisms of malarial immunity.

PMID- 15463096
TI  - Complement and evolution.

PMID- 15463098
TI  - The effects of parasitic infection on cognitive performance.

PMID- 15463099
TI  - Effect of calcium antagonists on malaria susceptibility to chloroquine.

PMID- 15463100
TI  - Mechanism of chloroquine resistance in malaria.

PMID- 15463101
TI  - Immunopathophysiology of Babesia bovis and Plasmodium falciparum infections.
AB  - Babesia bovis and Plasmodium falciparum are both vector-borne parasites primarily
      infecting the erythrocytes of their respective hosts. They have obvious
      differences, yet the diseases caused by these parasites share many common
      features. Both have generated a considerable body of research but, perhaps
      because of the classical distinction between veterinary and medical parasitology,
      many of the similarities between the two have been neglected. As this review
      shows however, many of the pathophysiological changes in B. bovis infections are
      poorly described for P. falciparum - and vice versa. Examples are the roles of
      lipid peroxidation, neutrophil adhesion and production of tumour necrosis factor
      (TNF) in malaria, which have been largely unstudied in babesiosis, or conversely
      the roles of fibronectin, immune complexes, cryofibrinogen and the complement
      cascade in babesiosis, which have been little studied (partly for ethical
      reasons) in human malaria. To clarify such questions, it may be that each of
      these diseases may serve as a partial model for the other.

PMID- 15463102
TI  - Helminth anti-oxidant enzymes: a protective mechanism against host oxidants?
AB  - Highly reactive oxygen species potentially represent a powerful effector
      mechanism against parasites. They are produced during normal cellular metabolism,
      especially by activated phagocytes, and also by some anti parasitic drugs. From
      studies to date, all protozoan and helminth parasites appear to have one or more
      anti-oxidant enzymes able to scavenge or quench the reactive oxygen species, and
      there is strong evidence that such enzymes play a crucial role in protecting
      against the host response. This detailed review, which summarizes studies on the
      major anti-oxidant enzymes of helminths, clearly illustrates that methods to
      block or overcome anti-oxidant protection may be a fertile field in the search
      for improved ways to inhibit parasite survival.

PMID- 15463103
TI  - Pharmacology of ivermectin.
AB  - Ivermectin is a semi-synthetic macrocyclic lactone (Fig. I) active in single low
      doses against many parasites - particularly nematodes and arthropods. It has been
      registered for animal health use since early 1985, and was earlier this year
      approved for human use by the French Directorate o f Pharmacy and Drugs. Of
      particular interest is ivermectin's potential as a micro filaricide for treatment
      o f onchocerciasis. Clinical trials leave little doubt about the potential o f
      ivermectin as a therapeutic tool for symptomatic relief from the effects o f
      infection with Onchocerca volvulus, and the drug is also recognized to have
      potential in reducing transmission o f the parasite. The manufacturers (Merck,
      Sharp and Dohme) recently arranged to provide the drug free o f charge to the WHO
      for mass trials against onchocerciasis in 12 African and Central American
      countries. In this article we focus on the pharmacological properties o f
      ivermectin, with a brief consideration of its absorption, fate, excretion and
      side-effects, and a discussion o f its micro filaricidal action.

PMID- 15463104
TI  - The cell biology of parasite invasion and survival.

PMID- 15463106
TI  - This wormy world.

PMID- 15463107
TI  - Entamoeba histolytica: from intestine to liver.

PMID- 15463108
TI  - Trypanosome reflections.

PMID- 15463109
TI  - Robert Michael Forde (1861-1948).

PMID- 15463110
TI  - Introduction of halofantrine for malaria treatment.

PMID- 15463111
TI  - Cuticular collagens - a concealed target for immune attack in hookworms.

PMID- 15463112
TI  - Dermatobia, the neotropical warble fly.
AB  - The neotropical warble fly, Dermatobia hominis (Fig. 1), has plagued neotropical
      America since preColombian times, and has become an economically important pest
      causing substantial losses to the meat, milk and leather industries from northern
      Mexico down to northern Argentina. Its life cycle (Box 1) is astonishingly
      complex, requiring another insect as a phoretic carrier of its eggs to the skin
      of its mammal hosts. Here Eugenio Sancho discusses factors that contribute to the
      current economic and public health importance of this myiasis-causing fly.

PMID- 15463115
TI  - Sheep flystrike and mulesing.

PMID- 15463113
TI  - Immunopathology of Entamoeba histolytica infections.
AB  - Entamoeba histolytica infects almost 10% of the world's population and results in
      about 100 000 deaths annually(1). Relatively little information is available
      concerning the immune response and the immunopathology elicited by this parasite,
      probably due in part to the lack of a truly appropriate animal model(2-4).
      However, there has been some progress - particularly concerning the interaction
      of this parasite with cells of the immune system(5,6). This review summarizes the
      salient features of the cellular immune response and immunopathology, largely
      from in vitro studies and studies using the gerbil model for invasive
      amoebiasis(7,8). Overall, the results suggest that invasive amoebtasis induces
      profound immune dysfunction both at the effector level of macrophages and on
      their accessory cell potential.

PMID- 15463116
TI  - Clerihewed taxonomy.

PMID- 15463117
TI  - Sex differences in infection.

PMID- 15463118
TI  - The lipophosphoglycan of Leishmania.
AB  - The major cell surface glycoconjugate of leishmanial parasites is
      lipophosphoglycan (LPG). Its relative abundance, unique structure, and cellular
      location suggest one or more important roles in interactions between parasites
      and host cells. In this article, Sam Turco examines current information about
      this novel glycoconjugate and its significance.

PMID- 15463119
TI  - Antigens and immunity in Theileria annulata.
AB  - About 200 million cattle are believed to be at risk from the debilitating and
      often fatal effects of tropical theileriosis, caused by Theileria annulata.
      Currently, there is no very cheap effective drug for treatment of T. annulata
      infections, although the hydroxynophthoquinones parvaquone and buparvaquone are
      reported to give good results(1-4). Control of the parasite principally involves
      vector control against the ixodid tick vectors - mainly by cattle dipping and
      spraying with acaricides - and vaccination using attenuated macroschizont
      infected leucocytes (1-17) (see Box I). In this article, Roger Hall discusses the
      nature of immunity that can be achieved against T. annulata, and progress in
      identifying the main antigens involved in this immunity.

PMID- 15463120
TI  - Differential diagnosis of eosinophilic meningitis.
AB  - Meningitis - infection o f the meninges - can be attributed to a variety o f
      agents, including bacteria, protozoa and some helminths. In helminth infections,
      but rarely in protozoal infections, eosinophilia is a common sign. Thus
      eosinophilic meningitis (EOM) is typically associated with certain helminth
      infections in which nervous system involvement occurs. Among the most important
      of these are ongiostrongyliosis, gnathostomiasis, porogonimiasis and
      cysticercosis (see Fig. 1). Here, Nibha Jaroonvesoma discusses the key
      distinctions between such infections.

PMID- 15463121
TI  - Cultivation of trematodes in chick embryos.
AB  - The chick embryo can be used as a substitute for adult animals in the cultivation
      of a variety of parasites. Bernard Fried describes its use in cultivating
      trematodes, and suggests that the system might be useful as a preliminary
      chemotherapeutic screen.

PMID- 15463122
TI  - RNA editing: new insights into the storage and expression of genetic information.
AB  - Kinetoplastid flagellates, and possibly other parasites and viruses, have evolved
      a novel form of gene regulation at different phases of their life cycle by
      'editing' their own RNA transcripts. This article discusses the significance of
      the process and proposes a hypothesis to explain how it may be done.

PMID- 15463124
TI  - Entamoeba histolytica: evasion and invasion.

PMID- 15463123
TI  - Diagnostic DNA amplification - not the complete answer?

PMID- 15463126
TI  - Bednets: the cannabis connection.

PMID- 15463128
TI  - Immunophysiology of enteric parasitism.
AB  - Capron and Dessaint have described the relationship between parasites and their
      hosts in terms of 'cell sociology'. In this review Gilbert Castro discusses the
      'sociological' aspects of functional associations among cells comprising the
      hollow organs of the gastrointestinal tract and the influence on them of enteric
      parasitism, and shows how such cells and tissues work in an integrated fashion to
      help the whole organism to maintain homeostasis under the stress of parasitic
      invasion.

PMID- 15463129
TI  - Complement and parasitic trematodes.
AB  - The complement (C) system acts as a barrier to protect our bodies against
      invading pathogens. It may react to cytophilic antibodies or directly to foreign
      molecules presented by the intruder. As well as their cytotoxic activity, C
      components can attract and attach leucocytes to the surface of the foreign body,
      and activate them to kill it. Zvi Fishelson describes various strategies used by
      a parasitic trematode to escape immune damage in the face of potent immune
      surveillance by C and other effector mechanisms.

PMID- 15463130
TI  - Immunoselection techniques for cloning DNA-encoding parasite-specific antigens.
AB  - New techniques sometimes generate a 'band- waggon' effect, with research workers
      keen to jump on and apply the technique in their own favourite field without
      always pausing to consider why. Michael Miles and Louise Clarke describe a new
      technique which they are applying to a well-defined and valuable end -
      improvement in the differential diagnosis of parasitic infections.

PMID- 15463131
TI  - Biological control of ruminant trichostrongylids by Arthrobotrys oligospora, a
      predacious fungus.
AB  - Sheep and cattle are prey to many parasitic worms, including the trichostrongylid
      nematodes. Conventional control involves the use of anthelmintic drugs, but in
      this article Hadji Ahmad Hashmi and Roger Connan discuss the possible biological
      control of these nematodes by means of a 'living lasso', the predacious fungus
      Arthrobotrys.

PMID- 15463132
TI  - New directions at the Danish Bilharziasis Laboratory.

PMID- 15463136
TI  - Parasite infections in AIDS.
AB  - 'Illnesses no one's got' was the epidemiological clue that led to the
      identification of AIDS as a new disease in 1981 when a rare infectious organism
      Pneumocystis carinii was seen in previously healthy homosexuals. Since then a
      wide range of parasite infections has been recognized in AIDS patients. However,
      these patients are not susceptible to just any passing parasite. The human
      immunodeficiency virus (HIV) produces a specific immune defect and only parasites
      that can exploit that defect will be able to flourish. In this review Diana
      Lockwood and Jonathan Weber explore the spectrum of parasite diseases recognized
      in AIDS and also consider those parasites that occur infrequently in AIDS.
      Analysis of parasitic infections that AIDS patients do not suffer from will yield
      valuable information about immune recognition and handling of these parasites.

PMID- 15463137
TI  - Genetic control of the immune repertoire in nematode infections.
AB  - Mammals vary considerably, both within and between species, in the way in which
      their innate and adaptive immune systems respond to infections. An understanding
      of the processes involved in such variability will not only contribute to
      explaining heterogeneity in susceptibility and pathology, but will also be
      relevant to vaccination. This will be particularly important for the new
      generation of vaccines that are likely to be composed of one or a few cloned or
      synthesized antigens. For helminth infections, this could have particular
      relevance to hypersensitivity responses. The adaptive immune response is
      fundamentally constrained by the genetic constitution of an individual, and the
      need to avoid reactivity to self. This will have important implications for the
      dynamic relationship between host defences and parasite evasion mechanisms at
      both physiological and evolutionary levels. In this review, Malcolm Kennedy
      examines the genetic control of the specificity of the immune response to
      nematode infections, and in particular, the role of the major histocompatibility
      complex.

PMID- 15463139
TI  - Haematoparasites and QBC analysis.

PMID- 15463140
TI  - Detoxifying esterases may limit the use of pyrethroids for malaria vector control
      in the Americas.

PMID- 15463141
TI  - Chloroquine resistance.

PMID- 15463142
TI  - Cardiac parasympathetic abnormalities: Cause or consequence of chagas heart
      disease?
AB  - The mechanisms by which Trypanosoma cruzi causes cardiomyopathy are unknown but
      are the subject o f several hypotheses. In this paper, Diego Davila, Osman
      Rossell and Jose Donis discuss the aetiology of cardiac failure in Chagas disease
      and suggest that parasympathetic abnormalities are a consequence of, rather than
      the cause of, the progressive cardiac enlargement seen in these patients.

PMID- 15463143
TI  - Methionine recycling as a target for antiprotozoal drug development.
AB  - The development of new and effective ontiprotozool drugs has been difficult
      because of the close metabolic relationship between protozoa and mammalian cells.
      In this article, Michael Riscoe, Al Ferro and john Fitchen present their
      hypothesis for chemotherapeutic exploitation of methylthioribose (MTR) kinase, an
      enzyme critical to methionine salvage in certain protozoa. They propose that
      analogues of MTR if properly designed, would be converted to toxic products in
      organisms that contain MTR kinase but not in mammalian cells, which lack this
      enzyme.

PMID- 15463144
TI  - Urinary schistosomiasis on Pemba Island: low-cost diagnosis for control in a
      primary health care setting.
AB  - In the 1970s and early 1980s indirect diagnosis of urinary schistosomiasis, using
      urinalysis reagent strips for proteinuria and haematuria, was proposed as a
      possible alternative to the more accurate but very time-consuming parasitological
      methods. The recent experience o f the Schistosomiasis Control Programme for
      Pemba Island, which used a combination of (1) observations o f grossly bloody
      urine specimens, (2) results from reagent strips for measuring haematuria, and
      (3) treatment with praziquantel, is the first large-scale example o f a simple,
      inexpensive and promising alternative for controlling the morbidity caused by
      this parasite.

PMID- 15463147
TI  - The Perils of water-resource development: Japanese encephalitis.

PMID- 15463148
TI  - Biological and immunological characteristics of Trichinella pseudospiralis.
AB  - In 1972 three new species were proposed for the genus Trichinella, which for 137
      years had contained a single species, Trichinella spiralis (Owen,1835). One of
      these proposed species, Trichinella pseudospiralis, was markedly different from
      the others in that it was smaller in size, the muscle-stage larvae were not
      surrounded by a capsule, and it was capable of parasitizing birds. Owing to a
      lack of information on the normal host range, geographic distribution,
      biochemistry, immunology and normal variation in biological characteristics of
      these organisms, several authors supported the more conservative position of
      designating them sibling species, subspecies or races of Trichinella. The summary
      statement following the session on Parasite Genetics and Speciation at the 7th
      International Conference on Trichinellosis recommended that pseudospiralis be
      accepted as a new species of Trichinella. In this article George Stewart reviews
      the available information on the biological and immunological characteristics of
      T. pseudospiralis.

PMID- 15463149
TI  - Protective immunity and vaccines to schistosomiasis.
AB  - Human schistosomiasis is a major health problem in endemic areas and it is
      estimated that world-wide more than 200 million people are infected. Active
      infection, exposure to attenuated parasites, or appropriate immunization with
      parasite extracts or purified antigens can lead to partial protection against
      challenge infections. Studies of the humoral and cellular mechanisms responsible
      for these forms of resistance, and the definition, purification or production of
      recombinant moieties responsible for the induction of immunity are currently the
      focus of considerable research efforts.

PMID- 15463150
TI  - American dog tick: vector of the Potomac horse fever Rickettsia, Ehrlichia
      risticii?

PMID- 15463152
TI  - Specific antibody response during the acute period of Chagas disease.

PMID- 15463153
TI  - Filariasis in history.

PMID- 15463154
TI  - Morphological types of Taenia solium cysticerci.
AB  - In human brain cysticercosis, there are three morphological types of cysticercus.
      Teresa Robielo, Angelica Rivas and Ana Flisser describe the appearance and
      possible taxonomic position of these forms, and discuss their relation to the
      various pathologies of neurocysticercosis.

PMID- 15463155
TI  - Infectious disease and the Unesco basic education initiative.
AB  - As part of a Basic Education for All campaign, Unesco is exploring ways to
      improve health and nutrition in school-age children in order to help them take
      advantage of the only schooling they may ever receive. At the first international
      Unesco working meeting on health, nutrition and school performance, intestinal
      helminths were identified as more appropriate immediate targets than malaria and
      other infectious diseases. Prevalence and intensity of infection in school-age
      children, the schools as vehicles of intervention, and the availability of
      interventions contributed to this choice. However, there are still many gaps in
      our knowledge of the effects of infectious diseases in schoolchildren. Through
      the improvement of understanding in this area, the parasitology community may be
      able to contribute to the Unesco project.

PMID- 15463156
TI  - The role of CD4+ T-cells in the immune response to Plasmodium chabaudi.
AB  - The development of protective immunity to Plasmodium requires the presence of T
      lymphocytes. This is obvious from many experimental models showing that
      parasitaernia cannot be controlled in T-cell-deficient animals. In addition,
      protection against plasmodia can be achieved in adoptive transfer experiments
      using specific T-cells from immune animals. In this brief article Jean Langhorne
      discusses the different responses of one particular subset of T-lymphocytes, the
      CD4(+) T-cells, to the parasite, emphasizing their role in the development of
      protective immunity to the erythrocytic stages of infection.

PMID- 15463157
TI  - Comment on the status of Echinococcus granulosus in the UK.
AB  - Echinococcus granulosus is composed of a complex of strains, the status of which
      has caused controversy and doubt. All have different characteristics which have
      arisen from animal husbandry practices, resulting in isolation and restriction of
      gene flow, and/or from the reproductive characteristics of the organisms.
      Whatever the mechanism for strain variation, Don McManus, Alan Lymbery and Andrew
      Thompson have no doubts that distinct variants occur in spite of a recent
      publication that suggests there is only one form of E. granulosus in the UK.

PMID- 15463158
TI  - Storage of filarial parasites in CsTFA and precipitation of filarial DNA using
      MTAB.
AB  - Immunological and biochemical studies on some parasite species are hampered by a
      limited availability of parasite material. Thomas Egwang Jean-Paul Akue and
      Margaret Pinder discuss a technique for preserving material from adult filarial
      worms during transport through endemic areas.

PMID- 15463160
TI  - Parasitology in Japan.

PMID- 15463161
TI  - Bovine trichomoniasis.
AB  - Although virtually unknown in Europe since the widespread adoption of artificial
      insemination (AI), infection by the sexually transmitted protozoan parasite
      Tritrichomonas foetus (Fig. 1) results in substantial economic losses throughout
      the major cattle-rearing areas of the world where natural breeding is relied
      upon. Infection by T. foetus is increasingly recognized as a significant cause of
      bovine infertility. In this review, Alex Yule, Susan Skirrow and Robert BonDurant
      summarize the current knowledge of bovine trichomoniasis and the problems of
      diagnosis and control of this economically important disease.

PMID- 15463162
TI  - Dormancy and hatching of nematode eggs.
AB  - The sequence of events during the hatching process of some parasitic nematodes
      has been the subject of recent detailed study. Certain factors, such as the
      trehalose content of the perivitelline fluid and the permeability characteristics
      of the eggshell, are influential in hatching and are also important for the
      survival of dormant, unhatched juveniles. In this review, Roland Perry examines
      some attributes of the egg that are involved in dormancy and survival of
      nematodes and details the changes that occur during the hatching process.

PMID- 15463164
TI  - Estimates of malaria incidence.

PMID- 15463165
TI  - The evolution of phylogenetic specificity among parasitic organisms.
AB  - It has long been recognized that, in some cases, the evolution of parasites seems
      to follow closely that of their hosts, yet in the literature dealing with host
      parasite evolution, the causes behind this Phylogenetic specificity (co
      evolution) are rarely addressed, the term 'parasite' is seldom clearly defined,
      and the diversity inherent in the nature of parasitism means that our
      'parasitophyletic rules' have often come under fire. In this article, Ian
      Humphery-Smith tries to give order to the discussion of this topic and outlines
      what sort of host-parasite relationships are most likely to produce Phylogenetic
      specificity.

PMID- 15463166
TI  - Schistosomiasis in Brazil: Does social development suffice?
AB  - Up to 15 years ago, when asked to identify the major public health problems of
      Brazil, there would be no hesitation in naming infant diarrhoea, Chagas disease
      and Schistosoma mansoni. While most field workers have now eliminated
      schistosomiasis from the list, now certainly headed by malaria, in academic and
      bureaucratic circles the old priorities are still maintained.

PMID- 15463167
TI  - The economics of malaria control in Thailand.
AB  - Economics has been variously described as the science concerned with the
      production, consumption and distribution of goods and services, the art of
      assessing values and, less flatteringly for economists, applied common sense.
      Irrespective of one's view, there can be little doubt about the basic issue.
      Resources available to a community are always scarce in relation to needs and
      aspirations and as a result, choices have to be made about how resources will be
      used, which requires economic evaluation. In addition, efforts have to be made to
      understand and improve the efficiency of existing operations by economic
      analysis.

PMID- 15463168
TI  - Multiple peptide synthesis (Pepscan method) for the systematic analysis of B- and
      T-cell epitopes: Application to parasite proteins.
AB  - In 1984 Mario Geysen and his colleagues described a technique for the
      simultaneous synthesis of hundreds of peptides on polyethylene rods. The
      peptides, still on the rods, could be used directly in enzyme-linked
      immunosorbent assays (ELISAs) and in this way linear parts of B-cell epitopes
      could be mapped. For the analysis of T-cell epitopes, peptides can be cleaved
      from the rods and incorporated into proliferation assays. This method, called the
      'Pepscan' procedure, has been used for the detailed characterization of epitopes
      of viruses, Chlamydia and Mycobacteria: it is a powerful new approach to the
      epitope mapping of parasite proteins.

PMID- 15463170
TI  - Malaria eradication in Chile.

PMID- 15463169
TI  - Towards standardized names for parasitic diseases.

PMID- 15463171
TI  - News from the WHO and the TDR special programme.

PMID- 15463172
TI  - George Hitchings and Gertrude Elion--nobel prizewinners.

PMID- 15463173
TI  - Glutathione S-transferases - potential components of anti-schistosome vaccines?
AB  - Graham Mitchell discusses how work in his and other laboratories has suggested
      that glutathione S-transferases may be potential candidate antigens for use in
      multicomponent anti-Schistosoma vaccines.

PMID- 15463174
TI  - Intra-specific variation in Schistosoma mansoni.

PMID- 15463175
TI  - How much malaria is there worldwide?

PMID- 15463177
TI  - The 'Ryan virus'.

PMID- 15463176
TI  - Parasitic worms in Nigerian folklore.

PMID- 15463178
TI  - Adjuvants for anti-parasite vaccines.
AB  - To date the most successful human vaccines use attenuated living pathogens, but
      the advent of techniques in genetic engineering has meant that pure antigen can
      be provided in quantity. This has allowed the development of combined vaccines
      that use only the parasite antigens that convey protective immunity. However,
      isolated antigens lose immunogenicity so to regain potency, living attenuated
      carriers like Vaccinia or Salmonella can be used. To avoid the attendant
      drawbacks of carriers as immunopotentiating agents, adjuvants are under
      investigation as alternatives for use in vaccines against parasitic infections.
      In this review, Robert Bomford describes the adjuvants currently being examined
      for use in vaccines for both protozoan and helminth infections including
      Leishmania, malaria and Schistosoma. He also points out the drawbacks of using
      adjuvants and the dilemma of needing to stimulate cell'-mediated immunity while
      avoiding the immunopathological consequences of doing so.

PMID- 15463179
TI  - Tick-host interaction: a synthesis of current concepts.
AB  - Ixodid ticks are recognized world-wide as major vectors of arboviruses,
      rickettsiae, spirochaetes and parasitic protozoa of man and domestic animals.
      Some ticks also inject a debilitating, sometimes fatal, paralytic toxin in their
      saliva. All these factors are transmitted via the salivary glands and mouthparts
      of the feeding tick. Tick feeding is a prolonged and complex process. Major
      developmental events occurring within the tick during feeding, as well as
      extensive tick-host interactions, all influence the likelihood of pathogen
      transmission. In this review, Reuben Kaufman discusses the sequence and
      complexity of these interactions.

PMID- 15463180
TI  - Biochemical resistance detection: an alternative to bioassay.
AB  - Insecticide resistance is an increasing problem in vector control programmes.
      Until recently, the usual means of detecting it has been by bioassay, requiring
      the use of relatively large numbers of insects and insecticide-impregnated test
      papers which may be difficult to prepare and store reproducibly. William Brogdon
      argues for the use of biochemical microplate assays which are cheaper and easier
      to use, permit up to 30 assays to be made on a single insect, and give more
      reproducible results.

PMID- 15463181
TI  - The dynamics of East Coast fever: a modelling perspective for the integration of
      knowledge.

PMID- 15463182
TI  - The isolation of nucleic acid from nematodes requires an understanding of the
      parasite and its cuticular structure.
AB  - As parasitology increasingly becomes the domain of molecular biologists, it is
      important to keep in mind that a fundamental understanding of the whole parasite,
      its structure and behaviour can help to solve complex problems of molecular
      biology. Hugh Dawkins and Terence Spencer discuss the preparation of DNA from
      filaform larvae of Trichostrongylus colubriformis and Ostertagia circumcincta and
      how a detailed knowledge of the morphology and life cycle of each parasite helps
      in this process.

PMID- 15463183
TI  - Iron and malaria.
AB  - Iron deficiency is common in the developing world; consequently, programmes of
      presumptive therapy and mass supplementation have been introduced in several
      countries. In this article Stephen Oppenheimer suggests caution, as recent
      evidence suggests that these practices may actually increase the likelihood of
      the subject developing patent malaria in endemic areas. This may be especially
      significant in infants, who are less likely to be immune to malaria, and in
      pregnant women, who are often routinely given iron supplements and in whom
      malaria may damage the foetus.

PMID- 15463184
TI  - The application of nuclear magnetic resonance spectroscopy to parasite
      metabolism.
AB  - Nuclear magnetic resonance (NMR) has become a valuable tool for the study of
      metabolism in a wide variety of biological systems. Its inherent advantages are
      that it is non-destructive and non-invasive. Observations can be carried out not
      only on extracts and media but also on whole cells and whole tissues under
      varying conditions and over varying times. The information gained gives
      considerable insight into cellular metabolism. There has been, to date,
      relatively little literature on the application o f NMR to the biochemistry of
      parasites, presumably reflecting the paucity of interfaces between
      parasitologists and NMR practitioners as well as the inherent difficulties in
      obtaining sufficient parasite material for NMR experiments. These difficulties
      are being overcome and William O'Sullivan, Michael Edwards and Raymond Norton
      believe that NMR has a great deal to offer those interested in parasite
      metabolism. In particular, it has the capacity to turn up the unexpected, on
      important factor as so many parasites appear to have developed their own
      variations on orthodox metabolic pathways.

PMID- 15463185
TI  - Reinfection after treatment of schistosome infections.
AB  - Today, chemotherapy has a central role in the control of schistosome infections.
      Although the costs involved may be high in relation to local expenditures on
      health, externally funded mass treatment programmes can lead to large reductions
      in the prevalence and intensity of schistosome infections. But the benefits of
      treatment to a community that has been involved in a mass chemotherapy programme,
      or to an individual patient seen in a health centre, will be limited if
      reinfection after treatment is rapid and intense. Despite the efficacy of the
      available drugs few, if any, control programmes based on mass chemotherapy have
      interrupted transmission and come anywhere near to eradicating schistosome
      infection.

PMID- 15463186
TI  - Tabanids as vectors of disease agents.
AB  - The Tabanidae are considered to be among the major Dipteran pests of man and
      animals worldwide, but this group is undoubtedly the least studied. There have
      been at least 137 genera and 4154 species of tabanids described to date. Yet,
      existing, active research programmes number, at most, 50 in systematics and
      distribution, 15 in economic entomology, and five in disease transmission. To
      redress the balance, Lane Foil discusses the entire spectrum of research on the
      transmission of infections by tabanids, both from the point of view of general
      factors affecting transmission dynamics, as well as the specific examination of
      candidate agents, from viruses to filaria.

PMID- 15463187
TI  - Rapid ribosomal RNA sequencing and the phylogenetic analysis of protists.
AB  - A newly described technique for rapidly obtaining the partial nucleotide sequence
      of ribosomal RNA is being applied to investigate phylogenetic relationships among
      living organisms. Alan Johnson and Peter Boverstock describe the importance of
      this method to parasitology in providing new information on the phylogenetic
      relationships of parasitic organisms previously placed in groups of convenience.
      The phylum Apicomplexo in particular, has been the object of much study using
      this technique, but the technology is likely to extend soon to the restructuring
      of the phylogenetic trees of many groups of parasites.

PMID- 15463188
TI  - Toxocara pteropodis and visceral Larva migrans.
AB  - The life cycle of Toxocara pteropodis is only the second in the genus to have
      been elucidated in detail as a result of its suspected role in an epidemic of
      human disease. Transmission of this species of nematode is not only faecal but
      also tronsmommory, and the third-stage larvae demonstrate a remarkable affinity
      for the host's liver. Experimental infections in primates indicate it is not
      likely to be a human pathogen, and a reappraisal of the original epidemic has
      provided an unusual alternative explanation.

PMID- 15463190
TI  - Gertrude Elion and George Hitchings.

PMID- 15463191
TI  - The scourge on the land.

PMID- 15463192
TI  - Dermatobia revisited or tickling cows with feather dusters.

PMID- 15463194
TI  - Antiparasitic drug design.

PMID- 15463193
TI  - Chagas disease: a model for the study of autoimmune diseases.
AB  - There are few natural animal model systems to study autoimmune disease caused by
      infectious agents; however, Trypanosoma cruzi infection of the mouse offers an
      excellent model for the induction of autoimmunity and its consequences. In this
      article Klaus Petty and Harvey Eisen explain that it is probably during the acute
      phase of the infection that the stage is set for the long-term pathology.

PMID- 15463195
TI  - Evolution in the pentastomids.
AB  - The Pentastomida, or tongue worms, form an aberrant group of annulated
      endoparasites little known to most parasitologists and veterinarians. Although
      there is no doubt of their affiliation to arthropods, textbooks often rank the
      Pentastomida as a separate phylum. Riley's many publications on the group have
      'promoted it from the realm of the completely unknown to the semi-obscure', but
      still much research is needed on their basic biology, as little is known about
      their biochemistry, ecology or their evolutionary relationships. This review by
      Rolf Haugerud is intended to inspire curiosity about the Pentastomida by
      discussing their evolution in relation to their phylogeny, host relationships,
      geographic distribution, transmission and impact.

PMID- 15463196
TI  - Detection of haematoparasites using quantitative buffy coat analysis tubes.

PMID- 15463198
TI  - Malaria and the major histocompatibility complex.

PMID- 15463199
TI  - Polymorphism in the circumsporozoite (CS) protein of Plasmodium falciparum.

PMID- 15463200
TI  - Ivermectin as a systemic insecticide.
AB  - Like many broad-spectrum drugs, the antiparasitic agent ivermectin is not equally
      effective in the treatment of all parasitic infestations. Predicting arthropod
      susceptibility relies not only on an understanding of insect and acarine biology,
      but also on an appreciation of the pharmacokinetic properties of the drug which
      can be profoundly influenced by host differences and pharmaceutical formulation.
      In this review, Helen Jackson attempts to explain the diverse number of
      ivermectin-induced effects observed among parasitic arthropods feeding on treated
      animals and aims to provide an overview of the current and future use of
      ivermectin in the systemic treatment and control of arthropod pests of livestock.

PMID- 15463201
TI  - Xenobiotic metabolism in helminths.
AB  - During its life cycle a parasite, like mammals and other organisms, comes into
      contact with a variety of toxic molecules. In mammals the main line of defence
      against such compounds is a group of oxidative enzymes that occur predominantly
      in the liver. Many of these oxidations are dependent on the haemoprotein
      cytochrome P-450 which serves as a terminal oxidase accepting electrons from
      NADPH and cytochrome [Formula: see text] . This review by Wendy Precious and John
      Barrett illustrates that in contrast to mammals, xenobiotic metabolism in both
      parasitic and free-living platyhelminths and nematodes is predominantly reductive
      and hydrolytic as the cytochrome P-450 system is absent. This is surprising since
      it is present in many groups including bacteria, fungi and protozoa, which
      suggests an ancient origin. The absence of the cytochrome P-450 system not only
      severely limits the ability of helminths to detoxify compounds but also limits
      their ability to activate prodrugs.

PMID- 15463202
TI  - Ryan virus and the lipovirus: Examples of Acanthamoeba (Hartmannella)
      contamination of cell cultures.

PMID- 15463203
TI  - Further contribution to giardiasis debate.

PMID- 15463204
TI  - Rice, a challenge to health.
AB  - Irrigation can bring enormous rewards to a hungry world. For example by allowing
      agriculture in arid and semi-arid areas, by extending the growing season, and by
      giving higher crop yields. The most extensively irrigated crop is rice. This is
      where problems arise, because as rice fields are usually flooded for long
      periods, they provide ideal breeding places for mosquito vectors. Here Mike
      Service discusses some o f the health hazards, in particular malaria, that are
      often associated with rice cultivation, and the environmental measures that are
      sometimes employed to combat these problems.

PMID- 15463206
TI  - The role of parasites in regulating host abundance.
AB  - It has been 11 years since Anderson and May demonstrated the theoretical ability
      of helminth parasites to regulate host population abundance. In this review we
      consider how their work has advanced our understanding of the role of parasites
      in host populations. In particular Marilyn Scott and Andy Dobson consider three
      questions. What is meant by regulation? Is there empirical evidence that
      parasites can regulate host population abundance? Is it possible to predict the
      sort of host parasite association where one is most likely to be able to detect
      parasites as a major regulatory force?

PMID- 15463205
TI  - Cellular immunity in crustaceans and the proPO system.
AB  - The molecular mechanism of cellular immunity in arthropods has until recently
      been largely unknown, but with the development of a technique to isolate and
      handle the different blood cell types of crustaceans and with the purification of
      several proteins associated with the so-called proPO system of freshwater
      crayfish the processes have now begun to be better understood. In this article
      Mats Johansson and Kenneth Soderhall discuss the function of the proPO system in
      cellular immune reactions in crustaceans and in particular the role of a protein
      with a molecular mass of 76 kDa, which has been shown to be involved in the
      communication between the different blood cell types of crayfish.

PMID- 15463207
TI  - Why do Plasmodium falciparumm-infected erythrocytes form spontaneous erythrocyte
      rosettes?
AB  - Plasmodium falciparum malaria is one o f the most widespread o f human parasitic
      diseases and is responsible for the deaths of several million people in
      subtropical and tropical regions o f the world. The interaction o f malarial
      merozoites with erythrocytes and the adherence o f infected erythrocytes to the
      endothelium are among the cellular interactions extensively studied to define
      candidate antigens for a blood stage vaccine. However, the exact mechanisms
      underlying the invasion o f erythrocytes by P. falciparum merozoites and their
      subsequent binding to endothelium are not yet understood. Here Mats Wahlgren,
      Johan Carlson, Rachonee Udomsangpetch and Peter Perlmonn discuss a novel
      cytoodherence phenomenon which may be o f great importance in this context, that
      is, the spontaneous binding o f uninfected erythrocytes to those infected with
      late-stage parasites (trophozoites/schizonts).

PMID- 15463208
TI  - Does Trypanosoma cruzi stress its vectors?
AB  - Trypanosoma cruzi seems to compete with its vector, Triatoma infestans, for
      nutrients. When starved the resistance of infected Triatoma is reduced but it is
      rarely affected i f it is given an adequate food supply. Infected individuals
      also might be more sensitive than uninfected bugs to other environmental stress
      factors. Gunter Schaub believes that the theory, that T. cruzi does not affect
      its vectors, should be re-examined.

PMID- 15463209
TI  - BCG: a modifier of immune responses to parasites.
AB  - The use of BCG (Bacille Calmette-Guerin) as an adjuvant is well-established for
      vaccination against leprosy and tuberculosis. Dominique Frommel and Phillippe
      Lagrange discuss the effects of BCG in the control of parasite infections,
      particularly leishmaniasis, and the possibility of the development of anti
      parasite recombinant BCG vaccines.

PMID- 15463210
TI  - The effects of host sex on transmission success.
AB  - A recent debate in Parasitology Today explored the causes of gender-related
      differences in parasite infection, examining epidemiological patterns on the one
      hand, and interactions between host sex hormones and the immune response on the
      other. In this article, Richard Tinsley focuses on the simplified ecology of a
      host-parasite system in a desert environment. This enables a clear separation of
      the factors determining the levels of host invasion (including host behaviour)
      from those that modulate the survival of established worm burdens (including host
      physiology).

PMID- 15463211
TI  - Methods for the determination of glycolipids as parasite antigens.

PMID- 15463213
TI  - Pre-erythrocytic stage malaria vaccine development: current status and future
      prospects.

PMID- 15463215
TI  - The mannitol cycle--a new metabolic pathway in the Coccidia.
AB  - A new metabolic pathway, known as the mannitol cycle, has been identified in the
      coccidian parasite Eimeria tenella. It appears that this pathway may be important
      for the production and utilization of energy reserves for the parasite. This
      pathway has not been found in any other animal system and was previously thought
      to be unique to fungi.

PMID- 15463216
TI  - The veterinary importance of nodular worms (Olesophagostomum spp).
AB  - The nodular worms (Oesophagostomum spp) are important parasites of food animals
      and primates. The archaic line that parasitizes pigs appears to be less
      pathogenic than the parallel evolutionary lines in ruminants and primates.
      Morphological types of O. dentatum in pigs and an apparent new host record for O.
      venulosum, which normally affects sheep and wild ruminants, in cattle suggests
      aggressive recruitment within the genus. The same Oesophagostomum spp occur in
      humans and in non-human primates but it is not clear which is the natural host.

PMID- 15463217
TI  - More about canapes.

PMID- 15463218
TI  - Mass treatment of schistosomiasis.

PMID- 15463219
TI  - More about the 'Ryan Virus'.

PMID- 15463220
TI  - Neurobiology of sleeping sickness.
AB  - The advanced stages of sleeping sickness are correlated with a spread of
      trypanosomes into the central nervous system (CNS), producing a disseminated
      encephalitis. Inflammatory reactions extend along the blood vessels causing
      perivascular cuffing, which consists of in filtrations and proliferations of
      lymphocytes and also increased numbers of astrocytes and microglia. Progress in
      our understanding of the functions of astrocytes suggests that they are efficient
      antigen-presenting cells, initiating and regulating the intracerebral
      inflammatory response and limiting parasite spread to the perivascular spaces.

PMID- 15463221
TI  - Red cell deformability and invasion by malaria parasites.
AB  - Malaria parasites enter red cells in a multi-step process involving attachment,
      membrane deformation, invagination and encapsulation. The molecular basis of red
      cell rigidity is examined by Geoff Pasvol and lain Wilson, and they discuss its
      effect on the efficiency of invasion by various Plasmodium spp.

PMID- 15463222
TI  - Diagnosis of Pneumocystis carinii pneumonia.
AB  - Pneumocystis carinii is the prime opportunistic pathogen of our time, the leading
      cause of fatal pneumonia in the increasing number of immunosuppressed subjects
      encountered on oncology and transplant programmes' and in subjects with the
      acquired immuno-deficiency syndrome (AIDS).

PMID- 15463223
TI  - Present situation of visceral leishmaniasis in China.
AB  - Visceral leishmaniasis or kala azar is a disease that is distributed world-wide
      from countries around the Mediterranean Sea to Africa, the Middle East, Asia and
      South America (Fig. 1). Visceral leishmaniasis was highly prevalent in China but
      since 1958, after a nationwide campaign, it has been brought under control. Only
      sporadic cases occur in the hilly and newly reclaimed desert areas in NW China.

PMID- 15463224
TI  - The acquisition of lipids by African trypanosomes.
AB  - Bloodstream forms of African trypanosomes are dependent on their host for fatty
      acids, choline and other components of membrane lipids. The bulk of their choline
      requirement is met by their ability to take up lysophospholipids from the host
      tissue fluids. Trypanosoma brucei has ocyltransferose and phospholipase A(1)
      activities for the metabolism of exogenous lysophospholipids. The rate of uptake
      of lysophospholipids can be controlled by changes in the extrocellulor
      concentration of fatty ocyl-coenzyme A, and this control has potential for
      chemotherapy.

PMID- 15463225
TI  - Applications of remote sensing to the identification of the habitats of parasites
      and disease vectors.
AB  - Remote sensing has been largely ignored in the identification of parasite and
      disease vector habitats. It has a number of advantages, both in improved control
      and understanding, and should be considered by more field-orientated scientists.
      Successful and potential applications involving mosquitoes, ticks, trematodes,
      and tsetse flies are briefly reviewed by Martin Hugh-Jones.

PMID- 15463226
TI  - Point mutations and pyrimethamine resistance in Plasmodium falciparum.
AB  - Pyrimethamine was first introduced as a prophylactic antimalarial in 1952, with
      the advantages of low toxicity and freedom from side-effects. As early as the mid
      1950s, parasite resistance to this compound had been reported from several areas,
      and it has since become widespread on all continents where malaria is found.
      Although it is still used for the suppression of infection, predominantly in
      conjunction with sulphone or sulphonamide drugs, even these combinations are now
      useless in many areas. Pyrimethamine resistance is less important globally than
      resistance to the major curative drug chloroquine, but it has long tantalized
      molecular parasitologists because pyrimethamine belongs to the only class of
      antimalarials for which the target molecule is unambiguously known.

PMID- 15463227
TI  - Leishmaniasis in Manaus, Brazil.

PMID- 15463228
TI  - The surface membrane 3'-nucleotidase/nuclease of trypanosomatid protozoa.
AB  - The plasma membrane of protozoan parasites has been the subject of intense
      research interest because it serves as the interface between the parasite and its
      host] This structure functions in the acquisition of nutrients, in the response
      to environmental signals, in the secretion and excretion of metabolites, in the
      recognition of host surfaces and in the avoidance of host-destructive factors
      including the components of the immune response. Recent technological advances,
      such as the use of monoclonal antibodies and recombinant DNA methodologies, have
      led to the identification of specific plasma membrane components and their
      coding; sequences, often in the absence of information regarding the
      physiological role of the component. In this article Michael Gottlieb considers
      the functional activity of o plasma membrane enzyme which has been identified in
      a number of protozoa belonging to the family Trypanosomatidae, and considers its
      adaptive significance and possible evolution in the different genera of this
      family.

PMID- 15463229
TI  - The global dispersal of Bancroftian filariasis.

PMID- 15463230
TI  - Why is malaria fever periodic? A hypothesis.
AB  - For poorly understood reasons, malaria parasites tend to develop in synchrony
      with each other in the asexual erythrocytic phase of infection, and this
      synchronization determines the periodic nature of malaria fever. There is
      evidence to suggest that fever might help to protect the host, while
      synchronization might provide counter-protection for the parasite. Dominic
      Kwiatkowski and Brian Greenwood propose that malaria fever may be of mutual
      benefit for parasite and host.

PMID- 15463231
TI  - Lung-phase immunity to Schistosomes: a new perspective on an old problem?

PMID- 15463232
TI  - Will the real target of immunity to schistosomiasis please stand up.

PMID- 15463233
TI  - Population biology of Trichostrongylus tenuis, a parasite of economic importance
      for red grouse management.
AB  - The caecal nematode, Trichostrongylus tenuis, is associated with dramatic
      decreases in the density of red grouse (Lagopus lagopus scoticus) resulting in a
      significant loss of sporting income to many upland estates in the UK. In this
      article Peter Hudson and Andrew Dobson describe the dynamics of the grouse-T.
      tenuis system, show that the parasites can cause population crashes and present
      preliminary findings from the development of new control methods.

PMID- 15463234
TI  - Sea lice--major pathogens of farmed atlantic salmon.
AB  - The most important metazoan parasites of farmed Atlantic salmon are the sea lice
      Lepeophtheirus salmonis and Caligus elongatus. Adults of these caligid copepods
      are responsible for serious damage to the skin of salmon, which may die unless
      treated with organophosphorus pesticides. Alan Pike presents what is known of the
      biology of these important pathogens and highlights the shortcomings of this
      knowledge in terms of useful insights which could lead to more effective control
      measures.

PMID- 15463235
TI  - Sandfly control: a simple method to reduce biting rates.

PMID- 15463237
TI  - Host specificity, host range and host preference.

PMID- 15463236
TI  - Blood sucking bugs.

PMID- 15463238
TI  - Leishmanicidal activity of amino acid and peptide esters.
AB  - Amino acid and dipeptide esters kill intracellular and isolated L. amazonensis
      amastigotes. Several o f the compounds also restrict the growth o f mouse lesions
      after intralesional administration. However, the esters are known to be toxic in
      vitro for monocytes and certain lymphoid cells. Michel Rabinovitch surveys the
      mechanisms o f the leishmanicidal activity, describes some structure--activity
      relationships, and discusses strategies for the design of compounds more
      selective for the parasite.

PMID- 15463239
TI  - Computer-aided identification of insect vectors.

PMID- 15463240
TI  - The evolutionary biology of parasitism.

PMID- 15463241
TI  - Laboratory models for research in vivo and in vitro on malaria parasites of
      mammals: Current status.
AB  - In research aimed at developing strategies for the eradication of human malaria,
      various species of rodent, avian and non-human primate plasmodia are used as
      laboratory models. Here Barend Mons and Robert Sinden attempt to summarize the
      most common laboratory models for mammalian malaria, and to shed some light on
      their applicability to different aspects of malaria research.

PMID- 15463242
TI  - Waterborne cryptosporidiosis.
AB  - Awareness of the importance of Cryptosporidium as a gastrointestinal parasite of
      developed countries not only stems from its prevalence in AIDS patients but also
      from its recent recognition as a possible contaminant of drinking water supplies.
      The importance of Cryptosporidium to public health has recently been revealed by
      a series of major epidemics of diarrhoeal disease in the USA and UK. In this
      review, Huw Smith and Joan Rose document what is known of the causes of some of
      these outbreaks and explain why this parasite can escape the battery of treatment
      processes normally used for drinking water supplies in these countries.

PMID- 15463243
TI  - Salmon farming in Scotland.

PMID- 15463244
TI  - Toxoplasmosis in AIDS.

PMID- 15463245
TI  - Banished bugs.

PMID- 15463247
TI  - The benefits of fish vaccines.

PMID- 15463248
TI  - The use of experimental artefacts in African trypanosome research.
AB  - When trypanosomes are removed from the field and maintained in laboratory
      conditions, phenotypic changes commonly occur such that the lines used by many
      investigators in routine work show several differences from the populations that
      affect humans and cattle in Africa. Whether these differences are important or
      irrelevant of course depends on the purpose of each particular experiment, but an
      awareness of what the differences are can be a useful aid in the interpretation
      of results. Furthermore, trypanosomes can be manipulated in the laboratory to
      possess particular characteristics that aid in the testing of hypotheses that are
      difficult to test using 'wild-type' trypanosomes. In this article, Mike Turner
      describes how some defined trypanosome lines have been created, how they differ
      from one another and several of their uses.

PMID- 15463250
TI  - A way round the 'real difficulties' of malaria sporozoite vaccine development?
AB  - Vaccines against the sporozoite stages of malaria, based on circumsporozoite (CS)
      protein epitopes, have had poor results in clinical trials. It has recently been
      suggested that attention should be switched to looking for new sporozoite, or
      hepatioc-stage proteins from which to develop vaccines. Here Francesco Sinigaglia
      and Richard Pink argue the case for reconsidering CS proteins as vaccines
      candidates.

PMID- 15463251
TI  - Interrupted feeding of blood-sucking insects: causes and effects.
AB  - The interruption of feeding of an arthropod vector can have important
      consequences for the transmission of blood parasites. In this article, Clive
      Davies explains the causes of feeding interruptions and how they are estimated,
      so as to assess the consequences to the fitness of a vector and the transmission
      success of its parasites.

PMID- 15463252
TI  - Trypanosomatid parasites of plants (phytomonas).
AB  - Trypanosomatids of the genus Phytomonas have been known as parasites of
      lactiferous plants since the beginning of the century and have been the subject
      of renewed attention in the past decade, as they are now recognized to be
      pathogenic in plants of economic interest. Nevertheless, information about these
      flagellates is still scanty. Until recently they had not been cultured, or
      studied biochemically or ultrastructurally. Phytophagous insects are their
      putative vectors but exactly which species are involved remains to be
      established. There are many unanswered questions about the taxonomic
      identification, pathogenecity and transmission of Phytomonas spp as well as about
      their natural hosts and reservoirs; this article by Erney Camargo, Pieter
      Kastelein and Isaac Roitman highlights some of them.

PMID- 15463254
TI  - Immune-facilitated drug action in schistosomiasis.

PMID- 15463253
TI  - Intestinal capillariasis.
AB  - What started out as an isolated report of an unknown intestinal parasitic disease
      has emerged as another disease of worldwide significance. Capillaria
      philippinensis was found in the intestines of a Filipino who suffered from an
      intractable diarrhoea and died in 1963. A few years later epidemics of intestinal
      cappillariasis erupted and spread to many parts of the Philippines. Thailand was
      also found to be endemic for the disease and in recent years, a few case reports
      have come from Japan, Iran and Egypt too. Since small freshwater and brackish
      water fish are considered to be the natural intermediate hosts, and fish-eating
      birds potential definitive hosts, John Cross suggests that the spread of the
      parasite may be attributable to migratory birds.

PMID- 15463255
TI  - Antigens on the Plasmodium falciparum infected erythrocyte surface are not
      parasite derived.
AB  - After invasion by Plasmodium falciparum a red blood cell undergoes marked
      alterations to its morphology and physiological properties. There are two schools
      of thought on the origin of these modifications: in the first of this pair of
      articles, Irwin Sherman and Enrique Winograd put the case for the changes to the
      surface proteins of the red cell being parasite-induced modifications to host
      proteins. They suggest that changes to naturally occurring host red cell
      proteins, especially band 3, result in subtle changes to the antigenicity,
      cytoadherence and to some extent to the morphology of infected red cells.

PMID- 15463257
TI  - Anisakis - from the platter to the microfuge.
AB  - Anisakiasis is a disease caused by the ingestion of anisakid nematodes in raw or
      improperly prepared fish dishes. Invading larvae penetrate the mucosa and
      submucosa of the gastrointestinal tract and produce lesions characterized by a
      marked inflammatory response. Judy Sakanari describes the biochemical and
      molecular studies on the proteins excreted and/or secreted by Anisakis larvae
      that are currently underway to help elucidate the role these proteins may play in
      the invasion process and the pathogenesis of anisakiasis.

PMID- 15463256
TI  - Antigens on the Plasmodium falciparum infected erythrocyte surface are parasite
      derived: a reply.
AB  - In this article Chris Newbold and Kevin Marsh describe the evidence for the co
      existence of both modified host proteins and of parasite determinants at the
      infected erythrocyte surface. The stable characteristics of infected cells may in
      part stem from parasite-induced changes in band 3 molecules, thus explaining some
      of the cytoadherence properties of uninfected, but abnormal cells (as in sickle
      cell disease and diabetes). However, Newbold and Marsh suggest that it is
      difficult to explain the astonishing diversity of antigens that have been
      observed at the surface of infected red cells unless such molecules have been
      synthesized by the parasite.

PMID- 15463258
TI  - A comparison of trans-RNA splicing in trypanosomes and nematodes.
AB  - Many aspects of the biology of kinetoplastids are unique, so it is surprising
      that they share with nematodes an unusual post-transcriptional process called
      trans-splicing. During this process, a small conserved RNA sequence is added to
      the 5' non-translated ends of transcribed RNAs of protein-encoding genes.
      Trypanosomes and nematodes are the only organisms to date in which these
      sequences have been described, and the biological significance of trans-splicing
      remains a mystery but may be of wider occurrence in invertebrates. In this
      review, John Donelson and Wenlin Zeng compare the process in nematodes and
      trypanosomes and speculate on its raison d'etre.

PMID- 15463259
TI  - Antimalarial drugs: is the lysosomotropic hypothesis still valid?
AB  - Although quinine and its congener chloroquine have been used as antimalarials for
      many years, and their analog, mefloquine, has been recently introduced, the
      precise mode of action of these quinoline-containing drugs is not fully
      understood. The lysosomotropic hypothesis is favoured and Hagai Ginsburg here
      discusses its principles and its reliability in view of both the physicochemical
      character of the drugs and new experimental evidence.

PMID- 15463260
TI  - Peter Abildgaard: forgotten pioneer of parasitology.

PMID- 15463261
TI  - National reporting of leishmaniasis: the Brazilian experience.
AB  - Leishmaniasis is one of Brazil's major disease problems. Notifications of
      cutaneous and visceral leishmaniasis given to the Ministry of Health over the
      past few years show that the problem is increasing.

PMID- 15463262
TI  - Trypanosome diversity in Lambwe Valley, Kenya-Sex or selection?

PMID- 15463263
TI  - Interpreting parasite host location behaviour.

PMID- 15463264
TI  - Intraspecific variation in parasites- what is a strain?
AB  - The use of molecular techniques in parasitology has revealed a startling degree
      of diversity within species of parasite. These discoveries have emphasized the
      need for parasitologists to define and describe accurately the organisms with
      which they work. Andrew Thompson and Alan Lymbery propose that parasite strains
      be described by a combination of genetic and biological characteristics since
      reliance on the genotype alone may confer significance on a feature of little
      biological relevance.

PMID- 15463265
TI  - Epidemiology of honey bee parasites.
AB  - The epidemiology of honey bee parasites has been somewhat neglected, but Lynn
      Royce and Philippe Rossignol describe their unique characteristics. Indeed, it
      appears that a parasite of social insects has in essence to adapt to two hosts:
      first, the individual worker within a colony, the numbers of which grow linearly
      and second, to the colony itself, the actual reproductive 'organism'.
      Transmission also has vertical and horizontal components. Analysis of tracheal
      mite populations in particular suggests that intracolony parasite levels are
      regulated by the swarming behavior of their hosts. Ironically, current and highly
      productive methods of honey bee management with movable hives curb swarming and
      may contribute to increasing the spread and the impact of some parasites. This
      insight may result in changing management practices to reduce the detrimental
      effects of bee parasites.

PMID- 15463266
TI  - In defense of behavioural host location.

PMID- 15463267
TI  - Trypanosome diversity in Lambwe Valley, Kenya-Sex or selection? Reply.

PMID- 15463268
TI  - Leaky livers, portal shunting and immunity to schistosomes.
AB  - In mice, concomitant immunity to schistosomes seems to be largely dependent on
      factors that lack immunological specificity. In this review Alan Wilson describes
      the anatomical changes stimulated in the host's vasculature after the formation
      of granulomas around schistosome eggs in the liver. The blockage of portal
      venules by the granulomas leads to portal hypertension and the development of
      anastomoses that direct blood flow, schistosomula and eggs from the liver. An
      intact portal vasculature is required for schistosome maturation; some strains of
      mice appear to be resistant to schistosome infection because they have a
      predisposition to form anastomoses in the absence of infection.

PMID- 15463269
TI  - Starlings as herbalists: countering parasites and pathogens.
AB  - The avian nest protection hypothesis explains the widespread behavior of
      incorporating fresh green plant material into an otherwise dry nest matrix as an
      evolutionary adaptation. Species that exhibit this behavior tend to breed in
      previously inhabited nest sites and experience high ectoparasite and pathogen
      loads. Metabolites in the green plants control parasite and pathogen populations
      and decrease the effects of these agents on nestlings. The choice of plants is
      not arbitrary. In the case of European starlings, a nonrandom subset of available
      vegetation is selected, and it is these plants that have the largest impact on
      ectoparasite and pathogen populations. Experimental and observational evidence
      suggests that starlings select plants on the basis of chemosensory cues.

PMID- 15463270
TI  - The peculiarities of Blastocrithidia triatomae.
AB  - Blastocrithidia triatomae parasitizes triatomine bugs, the vectors of Chagas
      disease. Co-cultivation with a host-derived cell line permits continuous culture
      but the host cells are destroyed. Removal of the reduviid cells induces the
      formation of drought-resistant cysts, but the factors that induce encystment are
      unknown. Excystment is triggered after the onset of blood digestion in the insect
      host, a transition that is associated with unusual ultrastructural alterations.
      Gunter Schaub, Dagmar Reduth and Mary Pudney believe that B. triatomae is a good
      candidate for the biological control of Chagas disease, not least because of its
      capacity to form highly resistant cysts in vitro.

PMID- 15463271
TI  - Cloning of schistosomes.
AB  - Before cloning was perfected, the only way to maintain schistosome strains was by
      sustaining the entire parasite cycle, ie. by ensuring the regular transmission of
      the parasite from the snail to the vertebrate, then from the vertebrate to the
      snail, and so on ad infinitum. Joseph Jourdane explains that by cloning the
      parasite in the snail and transplanting the larval parasite from snail to snail,
      the passage in vertebrates can be avoided indefinitely.

PMID- 15463272
TI  - Perspectives on the control of Taenia solium.

PMID- 15463273
TI  - Plasmodium falciparum surface antigen p l 90: prevalence of a nonrepetitive
      allele in humans.

PMID- 15463274
TI  - Resistance to parasitic nematodes - how is the MHC involved?

PMID- 15463275
TI  - Intestinal protozoa and epithelial cell kinetics, structure and function.
AB  - Intestinal protozoa are not only common enteric pathogens in the tropics but also
      the high incidence of infection among immunocompromised patients in northern
      countries has evoked an increased interest in these parasites. Although enteric
      protozoa are a major cause of diarrhea and malabsorption in humans and other
      animals, the pathophysiology of gut disturbances caused by them remains poorly
      understood. Clinical signs related to enteric protozoan disease commonly involve
      malabsorption, diarrhea, weight loss or retarded weight gain and anorexua. Since
      these infections are most prevalent and most severe in the young, this may
      translate into considerable illness among children and significant loss to the
      agricultural economy where domestic animals are prone to infection. In this
      review we describe the effects of intestinal protozoan diseases on the structure,
      kinetics and function of absorptive intestinal cells and other epithelial cells,
      and correlate morphological injury with physiological alterations in the
      parasitized gut. Some of the interactions between immune responses and
      pathophysiology will be discussed, but in-depth discussion of intestinal immunity
      has recently been undertaken by other authors.

PMID- 15463276
TI  - Parasitoids, polydnaviruses and endosymbiosis.
AB  - Symbiotic associations traditionally have been treated as evolutionary curios
      rather than as a major source of evolutionary innovation. Recent research on a
      wide variety of organisms is changing this view and is breaking down the barriers
      between the traditional categories of parasitism, commensalism and mutualism, to
      produce a more flexible view of multispecific interactions. An especially
      abundant, but little discussed, mutualism exists between parasitoid wasps in the
      superfamily Ichneumonoidea and a novel form of DNA viruses known as
      polydnaviruses. Mutualisms between viruses and eukaryotes are not often reported,
      although as many as 100 000 species of organisms may exhibit this unusual
      association. In this review Jim Whitfield considers what is known about the
      parasitoid-polydnavirus relationship and how (and from what) it might have
      arisen.

PMID- 15463277
TI  - Ecdysteroids in nematodes.
AB  - The occurrence of ecdysteroids (insect moulting hormones) in nematodes, albeit at
      low concentrations, has been firmly established. In addition to apparently
      stimulating moulting in a few species, exogenously applied ecdysteroids have now
      been shown to have interesting biological effects on meiotic reinitiation in
      oocytes and on microfilarial production in filariae. Although such effects
      demonstrate the feasibility of influencing nematode physiology with exogenously
      applied ecdysteroids, hitherto it has not been possible to demonstrate synthesis
      de novo of these steroids in nematodes. Thus, it remains to be established
      whether ecdysteroids are truly endogenous nematode hormones or merely represent
      compounds with strong biological activity. Nonetheless, there are indications
      that interference with the ecdysteroid system might be exploitable in the
      development of novel approaches to control of nematodes.

PMID- 15463278
TI  - Folate and cobalamin metabolism in Plasmodium falciparum.
AB  - During the past several years, Jerapan Krungkrai, H. Kyle Webster and Yongyuth
      Yuthavong have characterized the metabolic pathway of folate biosynthesis and
      folate-dependent reactions, including the cobalamin-dependent activity of
      methionine synthase, in P. falciparum grown in vitro. In this review, they
      discuss the implications of this work for understanding the mechanism of
      pyrimethamine resistance and the importance of cloning the dihydrofolate
      reductase gene. In addition, the role of cobalamin in P. falciparum will be
      considered. Interference with cobalamin use may represent a new target for
      combating the parasite.

PMID- 15463279
TI  - The major merozoite surface antigen (MSAI) of plasmodium falciparum.

PMID- 15463280
TI  - Prehistoric parasitism in Tennessee.

PMID- 15463281
TI  - Cercarial kissing marks-no superficial make-up.
AB  - In the presence of fluorochrome-conjugated lectins, the products of schistosome
      cercarial penetration glands can be visualized as distinct deposits, or 'kissing
      marks', at sites of attachment and attempted penetration of the host's skin.
      Ewert Linder has observed that 'kissing marks' are also recognized by antibodies
      present in the schistosome-infected host. This has raised the question of whether
      cercarial secretions or antigenically related products play a role within the
      infected host, and has motivated studies on the distribution of such antigens in
      the parasite at different developmental stages.

PMID- 15463282
TI  - Latin American workshop for the evaluation of DNA probes for Leishmaniasis.

PMID- 15463283
TI  - Transgenic mosquitoes: a future vector control strategy?
AB  - Transgenic mosquitoes may provide a new way of dealing with the old problem of
      diseases transmitted by insects. Although many technical, and perhaps ethical,
      problems associated with the wild-release of transgenic insects have yet to be
      overcome, Julian Crampton and colleagues explore the potential of this technology
      in the continuing battle to control insect-borne disease.

PMID- 15463285
TI  - Immune elimination of schistosomes.

PMID- 15463287
TI  - Japanese encephalitis.

PMID- 15463289
TI  - Application of remote sensing.

PMID- 15463290
TI  - Populations at risk.

PMID- 15463292
TI  - Malaria incidence.

PMID- 15463291
TI  - Schistosome surface antigens: developmental expression and immunological
      function.
AB  - It has long been held as axiomatic that antigens exposed on the surfaces of
      parasitic organisms are primary targets of protective immune responses. It is
      becoming apparent that not all protective schistosome antigens are surface
      antigens and that not all surface antigens are necessarily targets of protective
      immunity. Andy Simpson suggests that one of the factors that determines the
      immunological function of surface antigens may be developmental expression.

PMID- 15463293
TI  - Historic photograph.

PMID- 15463294
TI  - Schistosome carbohydrates.
AB  - Schistosomes are long-lived in their human hosts (with life-spans measured in
      years), despite being situated in the blood stream and therefore apparently fully
      exposed to a wide range of vigorous immunological responses. However, not only
      have these parasites evolved so as to prosper in the hostile environment of their
      definitive host, but they also have to negotiate very different environments
      during the free-living and intermediate host stages of their life cycle. At each
      stage, surface, or secreted carbohydrates appear to play an important role in the
      parasite's interaction with its environment.

PMID- 15463295
TI  - The Cytoskeleton of trypanosomes.
AB  - From the concept of cells as mere bags full of enzymes, cell biology has come a
      long way towards understanding the highly complex structural organization of
      eukaryotic cells. The cytoskeleton, ie. the complex of fibrous elements that are
      crucial for cell shape, motility and the structural organization of cytoplasm and
      cell membranes, is now recognized as vital for supporting many critical functions
      in eukaryotic cells. Surprisingly, this subject, which has provided scores of
      cell biologists with excitement and fascination, has been largely overlooked with
      respect to parasitic protozoa. A notable change of perception has taken place
      over the past few years as the cytoskeleton of parasitic protozoa has been
      increasingly recognized as a potential target for antiparasitic intervention. The
      following article by Thomas Seebeck, Andrew Hemphill and Durward Lawson
      highlights some recent developments in the analysis of what is presently the best
      studied parasite cytoskeleton, that of the trypanosome.

PMID- 15463296
TI  - The giardins of Giardia lamblia: genes and proteins with promise.
AB  - The unique evolutionary position of the genus Giardia recently came to light when
      Mitch Sogin and colleagues showed it to be the earliest diverging lineage in the
      eukaryotic line of descent by ribosomal RNA analysis. Similar in significance,
      the acquisition of a cytoskeleton was a pivotal occurrence in evolution. With an
      endoskeleton came an internal support structure for cells as well as the means to
      regulate dynamic phenomena such as muscle contraction, mitotic movement of
      chromosomes, ciliar and flagellar beating, and cell migration. Debra Peattie has
      been exploring genes that express proteins of the Giardia cytoskeleton, and from
      this work she presents predictions of their structure and some thoughts about
      their function.

PMID- 15463297
TI  - Ribosomal RNA: nature's own polymerase-amplified target for diagnosis.
AB  - The technological criteria for diagnostic tests for tropical diseases are strict
      and limited. One method of considerable potential for field use is the
      exploitation of regions of species-specific sequences of ribosomal RNA (rRNA).
      Oligodeoxynucleotide probes can be used to detect the specific RNa regions in
      question. Andy Waters and Tom McCutchan describe how simple rRNA methodologies
      for Plasmodium can detect and identify parasites as well as follow different
      stages in their development. The potential of this methodology extends to
      monitoring both epidemiological parameters and the efficacy of novel drug
      regimes.

PMID- 15463298
TI  - Polymorphism in the circumsporozoite protein and anti-sporozoite malaria
      vaccines.

PMID- 15463299
TI  - The epidemiology of schistosome infections of snails: taking the theory into the
      field.
AB  - Most field studies of the epidemiology of schistosome infections of snails have
      been essentially descriptive in nature. Although much use has been made of
      epidemiological models in the interpretation of experimental studies of
      schistosome-snail interactions, the models have had restricted application
      outside the laboratory. Here, Mark Woolhouse and Steve Chandiwana make use of a
      theoretical framework in discussing current understanding of schistisome-snail
      epidemiological patterns in the field, and then consider the implications of the
      analysis for the control of schistosomiasis.

PMID- 15463300
TI  - Genetic exchange in Trypanosoma brucei.
AB  - The discovery of genetic exchange in African trypanosomes belonging to the
      Trypanosoma brucei group is an important development in our understanding of
      these organisms. Genetic exchange is a feature of major importance in relation to
      population structure and speciation. Furthermore, a convenient laboratory-based
      mating system would be of considerable value as a tool in trypanosomiasis
      research. It is now known that although cyclical development of trypanosomes
      within the tsetse fly does not require mating to occur, genetic exchange may take
      place under Conditions in which genetically distinct trypanosomes develop within
      the same fly. During the past few years there has been a considerable body of
      research on laboratory crosses, and a number of controversial and apparently
      contradictory models of the mechanism of genetic exchange and the ploidy of
      different life cycle stages have been proposed. In this article, Andy Tait and
      Mike Turner review the present state of knowledge regarding gene exchange in T.
      brucei, and attempt to reconcile the various observations and models available.

PMID- 15463302
TI  - Polymorphism and malaria vaccines.

PMID- 15463301
TI  - Pyrimethamine resistant?

PMID- 15463303
TI  - Chloroquine as intercalator: a hypothesis revived.
AB  - The mode of action of chloroquine is still controversial. Proposed mechanisms of
      action include (1) DNA intercalation, (2) lysosome accumulation and (3) binding
      to ferriprotoporphyrin IX. Recent data suggest that intercalation into parasite
      DNA can occur at physiological concentrations of the drug. Furthermore, structure
      activity relationship studies are most consistent with the intercalation
      mechanism. Regardless of which mechanism is correct, the selective toxicity of
      chloroquine for malaria parasites is probably due to permease-mediated uptake.

PMID- 15463304
TI  - The procyclin coat of African trypanosomes (or the not-so-naked trypanosome).

PMID- 15463305
TI  - Onchocerciasis (river blindness)- can it be eradicated?
AB  - Onchocerca volvulus causes a disease of significant socio-economic importance in
      West Africa, the Arabian Peninsula and regions of South America. Brian Duke
      explains that, despite the advent of ivermectin, the prospects for the
      eradication of this potentially highly debilitating infection are remote.
      Moreover, the logistical problems associated with the control of morbidity caused
      by the parasite are considerable, and are highly dependent on the ability to
      sustain financial support and political will over many decades.

PMID- 15463306
TI  - Pulse radiolysis, free radicals and antiparasitic drugs.
AB  - Free radicals have been proposed to be of significance in several important
      aspects of parasitology because of their generation during parasitic infection
      and chemotherapy, and their potential for causing cellular damage. Roger Bisby
      describes how radiation chemical methods, and pulse radiolysis in particular, may
      be used to generate and study free radicals that are of interest in parasitology.

PMID- 15463307
TI  - Helminths: primary models for comparative biochemistry.

PMID- 15463308
TI  - Helminths as heirlooms and souvenirs: a review of new world paleoparasitology.
AB  - Evidence from studies on ancient human feces, intestinal contents and organs of
      preserved bodies has established that Enterobius vermicularis, Trichuris
      trichiura, Diphyllobothrium spp and probably Trichinella spiralis infected humans
      in the pre-Columbian New World. These species, and perhaps other common human
      helminths for which there is not yet convincing evidence, probably accompanied
      transberingeal immigrants and their dogs, and thus can be seen as heirloom
      parasites. Early humans on the American continents were affected by helminths of
      native animals such as Paragonimus and Cryptocotyle, and these have also been
      found in precontact human remains. Michael Kliks considers that the indigenous
      parasites infecting early Americans may be viewed as zoonotic souvenirs of some
      50 millennia of migrations from Alaska to Patagonia. Among the most serious
      zoonoses would have been infection by cystic hydatid larvae of echinococcid
      tapeworms, the many enzootic filarial worms, and a variety of larval trematodes
      and nematodes.

PMID- 15463309
TI  - Climate, vegetation and the distribution of Rhipicephalus appendiculatus in
      Africa.

PMID- 15463310
TI  - Benzimidazoles in a wormy world.

PMID- 15463311
TI  - The synthesis and chemistry of certain anthelmintic benzimidazoles.
AB  - A basis for interest in the benzimidazole ring system as a nucleus from which to
      develop potential chemotherapeutic agents was established in the 1950s when it
      was found that 5,6-dimethyl-l-(alpha-D-ribofuranosyl)benzimidazole (I) was an
      integral part of the [structure: see text] structure of vitamin B(12). As a
      result of these interests and extensive studies, one health related arena that
      has benefited greatly has been the treatment of parasitic diseases. The discovery
      of thiabendazole in 1961 further spurred chemists around the world to design and
      synthesize several thousand benzimidazoles for screening for anthelmintic
      activity but less than twenty of them have reached commercial use. Much of this
      work has been done by pharmaceutical companies and is only reported in the patent
      literature. In this paper, Leroy Townsend and Dean Wise review the development of
      some of the synthetic methods that have been critical to the preparation of the
      benzimidazoles of anthelmintic importance. Only a few molecules that demonstrate
      the processes are discussed here, but numerous reviews of the synthesis and
      chemistry of other benzimidazoles are available.

PMID- 15463312
TI  - Mode of action of benzimidazoles.
AB  - Benzimidazoles represent the only class of truly broad-spectrum anthelmintics,
      however, they also show activity against fungi and mammalian cells. This raises
      the question as to why benzimidazoles can selectively kill helminths and yet
      exhibit little or no mammalian toxicity. In this paper, Ernest Lacey examines
      this example of selectivity of drug action to the ubiquitous target of these
      drugs, the structural protein, tubulin.

PMID- 15463313
TI  - The metabolism of benzimidazole anthelmintics.
AB  - The benzimidazole carbamates are important broad-spectrum drugs for the control
      of helminth parasites in mammals. David Gottschall, Vassilios Theodorides and
      Richard Wang explain that the metabolism of these compounds depends heavily on
      the substituent present on carbon-5 of the benzimidazole nucleus and involves a
      wide variety of reactions. Work in vitro has shown that two major enzyme systems,
      the cytochrome P-450 family and the microsomal flavin monooxygenases are
      primarily responsible for these biotransformations. The parent compound is
      generally short-lived and its metabolites predominate in the tissues and excreta
      of treated animals. The metabolic pathways can be exploited therapeutically to
      overcome the problems of poor water solubility and adsorbtion of benzimidazoles
      by the development and use of more soluble prodrugs.

PMID- 15463314
TI  - The molecular nature of benzimidazole resistance in helminths.
AB  - The economic importance of benzimidazole (BZ) resistance has resulted in the
      isolation of resistant populations of helminths and their study (see pp 127-129
      this issue). Recent research indicates that BZs act by binding to free beta
      tubulin in the cell and inhibiting the formation of microtubules. The effects of
      BZs on other processes in the cell, such as transport and anaerobic metabolism,
      probably result from the inhibition of one or more of the functions of tubulin
      (see pp 112-115, this issue). In this article, Marleen Roos examines the evidence
      for changes in the beta-tubulin structure and the rate of its synthesis in BZ
      resistant parasitic nematodes.

PMID- 15463315
TI  - Resistance in nematode parasites of livestock to the benzimidazole anthelmintics.
AB  - The benzimidazoles have served humans well in the continual battle to control
      nematode parasites among livestock. However, the value of these drugs has been
      seriously undermined in various countries, particularly in the southern
      hemisphere, by the development of resistance in the target parasite species.
      Scientists in many countries are trying to come to grips with this problem, with
      studies both in the laboratory and the field. However, there are shortcomings
      with both approaches, particularly the former, which need to be recognized. In
      this article, Peter Waller discusses these in relation to research into the
      experimental and epidemiological aspects of benzimidazole resistance.

PMID- 15463316
TI  - Benzimidazoles: veterinary uses.
AB  - Benzimidazoles are valued for use against helminth infections in domestic
      animals. Here, Bill Campbell discusses efficacy, dosages, methods of
      administration and the species of parasite against which they are applied.

PMID- 15463317
TI  - Use of benzimidazole chemotherapy in human helminthiases: indications and
      efficacy.
AB  - The past two decades have seen some remarkable developments in anthelmintic
      chemotherapy in clinical medicine. Whereas praziquantel has revolutionized the
      management of many cestode and trematode infections, Gordon Cook explains how the
      introduction of the benzimidazoles - most importantly thiabendazole, mebendazole
      and recently albendazole (flubendazole, cambendazole, ciclobendazole, and
      triclabendazole have also been used on a very limited scale) - has had a major
      impact upon the safe and effective management of several important intestinal and
      systemic nematode and, to a leser extent, cestode infections.

PMID- 15463318
TI  - The wise eye of hindsight.

PMID- 15463319
TI  - Diagnosis of Chagas disease using recombinant DNA technology.
AB  - In this article, Alberto Frasch and Maria Reyes discuss the development of new
      tools for the serodiagnosis of Chagas disease (caused by Trypanosoma cruzi) and
      describe recombinant antigens that have proved to be of great diagnostic
      potential in distinguishing different stages of the disease. The work is
      important because different treatment strategies are needed for acute and chronic
      infection.

PMID- 15463320
TI  - Schistosome surface protein anchors.

PMID- 15463321
TI  - Ascariasis in Nigeria.
AB  - Nigeria is the most populous country in Africa and projections for the future
      indicate that the population could reach about 165 million by the year 2000(1). A
      high proportion of the population is under 15 years of age and the majority of
      people still live in rural areas(1). These characteristics, in combination with a
      socioeconomic environment influenced by poverty, poor housing, insufficient
      sanitation and a need for health education, favour the transmission of the human
      roundworm Ascaris lumbricoides. In 1986, a WHO report on the prevalence of
      ascariasis in Africa singled out Nigeria for special comment: 15 million
      Nigerians are estimated to harbour Ascaris. In this context, and that of their
      own recent field studies, Celia Holland and Samuel Asaolu review the present
      state of knowledge of ascariasis in Nigeria.

PMID- 15463323
TI  - Rosette formation?

PMID- 15463322
TI  - Entomopathogenic rhabditid nematodes and pest control.
AB  - Imagine an insecticide that is effective against insects in cryptic habitats, has
      a wide spectrum of efficacy, is cheaply produced by high technology or cottage
      industry and hence is suitable for developing and developed countries, is non
      toxic to vertebrates and plants, and persists at low levels in natural habitats.
      This is not a dream. These properties apply to a group of entomopathogenic
      nematodes belonging to the rhabditid families Steinernematidae and
      Heterorhabditidae. Bill Hominick reviews developments in the use of these
      nematodes for the control of insect pests. His article represents a departure in
      philosophy for parasitologists, in that entomophilic nematologists are devoted to
      increasing, rather than decreasing the number of nematodes in the environment.

PMID- 15463325
TI  - Filariasis discovery.

PMID- 15463327
TI  - An immunological and biochemical comparison of hookworm species.
AB  - The successful development of diagnostic tests capable of distinguishing human
      hookworm species will ultimately depend on an increase in our knowledge of their
      comparative biochemistry. Here, David Pritchard, Paul McKean and Gerry Schad
      describe some aspects of the comparative biochemistry of Necator americanus and
      Ancylostoma duodenale, and emphasize differences between the species that could
      form the basis of discriminatory diagnostic tests.

PMID- 15463328
TI  - The role of vector saliva in transmission of arthropod-borne disease.
AB  - Blood-sucking arthropod disease vectors all share one important feature: while
      probing for blood in the vertebrate host's skin they salivate into the wound they
      create. Recent studies on the pharmacological properties of vector saliva have
      revealed an array of activities that are potentially beneficial to both the
      vector and to the pathogen. These observations may help explain why certain
      vectors and pathogens have co-evolved. In this article, Richard Titus and Jose
      Ribeiro discuss the role vector saliva may play in disease transmission, and the
      prospects for its use in the control of arthropod-borne pathogens.

PMID- 15463329
TI  - Why do schistosomes have separate sexes?
AB  - Paul Basch postulates that the familiar Schistosoma of humans evolved from
      hermaphroditic blood flukes of Mesozoic reptiles as those host became warm
      blooded. The reproductive superiority that accompanied tendencies to protandry
      and protogyny in hermaphroditic blood flukes has led to subsequent sexual
      separation and dimorphism but substantial fragments of the ancestral contrasex
      genome persist in present-day males, as shown by common tendencies toward
      hermaphroditism. In present-day females the loss of the male-specific genome is
      far more complete and in the process of optimizing reproductive efficiency,
      present-day females have sacrificed many structural elements including locomotory
      and pharyngeal muscles. These losses have created dependency on the well-muscled
      male, whose primary functions seem to be compensatory; ie., physical transport of
      the female from the point of pairing to the point of egg deposition, stimulating
      growth and development by pumping blood into the female, who unpaired would
      starve, plus, less importantly, fertilization of the oocytes.

PMID- 15463330
TI  - A role for pore-forming proteins in the pathogenesis by parasites?
AB  - Over the past decade or so, pore-forming proteins (PFPs) have been isolated from
      various immune cells and nonpathogenic bacteria. It is now becoming apparent that
      PFPs may also be produced by a number of parasites. Although far from definitive,
      the evidence currently available for the role of PFPs in the survival and
      pathogenesis by parasites in briefly presented by David Ojcius and John Ding-E
      Young.

PMID- 15463331
TI  - Human schistosomiasis in India?
AB  - It was a common belief in the first half of this century that human
      schistosomiasis would not become established in India, despite the regular
      introduction of the disease by soldiers returning from active campaigns. This was
      based on the absence of known intermediate hosts for Schistosoma spp, yet in 1952
      a focus of human schistosomiasis was discovered in Gimvi village, Ratnagiri
      District, Maharashtra State. The focus seems to be in recession, but the proposed
      large irrigation schemes centering upon the Narmada River may exacerbate
      schistosomiasis in domestic stock, and possibly in humans. Here, Vaughan
      Southgate and Matesh Agrawal discuss the findings in Gimvi, and the possibilities
      of human schistosomiasis in India in the future.

PMID- 15463332
TI  - Calcium binding proteins in schistosomes.

PMID- 15463333
TI  - Water resources development policies, environmental management and human health.

PMID- 15463334
TI  - Immune mechanisms in trematode-snail interactions.
AB  - Digenetic trematodes, including several species of medical and veterinary
      significance, nearly all depend on molluscs (usually gastropods) as hosts for
      asexual reproduction. The molluscan internal defence system, although lacking
      many of the familiar features of the vertebrate immune system, may pose a
      substantial obstacle to digenean development. In this article, Wil van der Knaap
      and Eric Loker discuss the manner in which this system is mobilized to kill
      larval trematodes and the real and putative mechanisms of digenean evasion of
      molluscan immune responses. These two possible outcomes of trematode-snail
      associations make them intriguing model systems for exploring processes of
      parasite infectivity and host resistance.

PMID- 15463335
TI  - Evasion strategies of Leishmania parasites.
AB  - Leishmania have long been known to clinicians and parasitologists as the
      causative agents of a variety of acute or chronic, cutaneous or visceral diseases
      in mammalian hosts. More recently, these protozoan parasites have evoked the
      interest of immunologists, as Leishmania infections are an excellent model for
      studying T-cell dominated antiparasite immune responses. In this review,
      Christian Bogdan, Martin Rollinghoff and Werner Solbach discuss the multiple
      interactions of Leishmania with components of the host immune system that
      illustrate the variety of highly elaborate evasion strategies developed by this
      parasite.

PMID- 15463337
TI  - Population at risk.

PMID- 15463336
TI  - Interrupted feeding of vectors.

PMID- 15463339
TI  - The potential of Capillaria hepatica to control mouse plagues.
AB  - The potential of helminths as bio-control agents of mammalian pests has been
      largely ignored. However, the nematode Capillaria hepatica is currently being
      examined for its potential to control population outbreaks of house mice in
      Australia. Grant Singleton and Hamish McCallum discuss laboratory and ecological
      studies of the parasite and host, and describe the results of two models that
      explore the interaction between C. hepatica and mouse populations.

PMID- 15463340
TI  - Trichinella spiralis: the worm that would be virus.
AB  - Trichinella spiralis is one of the world's largest intracellular parasites.
      Unlike most such organisms, it does not kill the host cell, but induces
      modifications in cell structure that enhance its own survival. In this article,
      Dickson Despommier describes the ways in which the parasite uses the cell for its
      own benefit, and discusses the extent to which this behaviour has contributed to
      the parasite's success.

PMID- 15463342
TI  - Biological control of pests and vectors: pros and cons.

PMID- 15463341
TI  - Calcium metabolism in malaria-infected erythrocytes.
AB  - Changes in the concentration of free calcium regulate many intracellular
      metabolic pathways and other important aspects of cellular function. The
      erythrocyte maintains intracellular calcium concentrations within a narrow range,
      but infection by malarial parasites disrupts these homeostatic mechanisms. The
      observation that infected erythrocytes have supranormal concentrations of calcium
      raises questions about the storage and functions of calcium ions within
      parasites. These are addressed in the following review by Sanjeev Krishna and
      Laura Squire-Pollard.

PMID- 15463343
TI  - Molecular biological approaches towards immunodiagnosis of filariasis.

PMID- 15463344
TI  - Parasitology in France: future trends.

PMID- 15463345
TI  - Parasitology in France: some aspects of the present.
AB  - Numerous organizations participate and cooperate on parasitological research in
      France including the Institut national de la Sante et de la Recherche Medicale
      (INSERM), the Centre national de la Recherche Scientifique (CNRS), the Institut
      Pasteur, the Institut Francais de Recherche Scientifique pour le Developpement en
      Cooperation (ORSTOMM), the Institut national de la Recherche Agronomique (INRA),
      the Museum national d'Histoire naturelle (MNHN), the Universities, the College de
      France, the Ecole Pratique des Hautes Etudes (EPHE) as well as various commercial
      firms. Exchanges and collaborations with foreign workers are continuous and
      essential to the success of research on tropical diseases. Here, in their own
      words, Odile Bain, Daniel Camus and Jacques Prod'hon highlight some aspects of
      current parasitological research in France.

PMID- 15463346
TI  - Parasitology in France: the past.
AB  - The 'French School of Parasitology' has its roots in the thirteenth century.
      Since then, it has contributed much to our understanding of parasitic organisms,
      their biology and their role as etiological agents of disease. In many fields of
      parasitology, the names of members of this school remain associated with
      taxonomic groups or species and they include two Nobel Prize winners, yet today,
      the origins of these names and the efforts of these early parasitologists have
      too often been forgotten. Here, Ian Humphery-Smith, Jean Theodorides, Louis
      Touratier and Anne-Marie Le-Flohic outline the highlights of the French
      contribution to our knowledge of host-parasite relationships.

PMID- 15463347
TI  - Glucose transport in malaria infected erythrocytes.
AB  - Intracellular protozoan parasites of the genus Plasmodium spend much of the cell
      cycle inside the vertebrate host's erythrocytes. Recent studies on the metabolism
      of D-glucose in Plasmodium-infected erythrocytes have suggested that the parasite
      does not depend on the glycolytic activity of the host erythrocyte. Kazuyuki
      Tanabe describes how the intraerythrocytic parasite acquires extracellular D
      glucose from the host and the pathways through which the sugar crosses the
      membranes of both the parasite and the host eruthrocyte. It appears that the
      parasite adapts itself to the host's physiological environment and modifies the
      functions of the host erythrocyte to be able to complete intraerythrocytic
      development.

PMID- 15463349
TI  - Chloroquine as intercalator: should this hypothesis be revived?

PMID- 15463350
TI  - Reproductive strategies and disease susceptibility: an evolutionary viewpoint.
AB  - Arguments about which constitutes the 'weaker sex' notwithstanding, sex
      differences in mortality and disease susceptibility have been noted in many
      species of animals, including humans. In this article, Marlene Zuk examines the
      possible reasons for these differences, relating them to reproductive strategies,
      and suggests how they may have resulted from selective pressures.

PMID- 15463351
TI  - Habitat selection by helminths: a hypothesis.
AB  - How do liver worms find the liver? Why are heartworms always found in the heart?
      Attempts to answer these questions have invariably yielded inconclusive results.
      A major problem has been the use of models or hypotheses derived from studies of
      free-living organisms. The parasite's environment is distinct from free-living
      environments in several fundamental ways and these differences will impact on the
      evolution of parasite behaviours. In this article, Michael Sukhdeo outlines a
      hypothesis for habitat selection behavior of helminths that is based on the
      specific environmental conditions within the host.

PMID- 15463352
TI  - Biological methods for the control of freshwater snails.
AB  - As a result of the advent of new drugs and diagnostic techniques, the emphasis in
      the control of schistosomiasis has changed from snail control to chemotherapy for
      infected individuals. However, chemotherapy does not prevent reinfection and
      there remains a need to reduce snail densities in human water supplies. In the
      past, treatment with molluscicides has proved ineffective, expensive and has had
      environmental drawbacks. Here, Henry Madsen describes research into alternative
      methods of snail control. As yet, little is known of the predators and parasites
      of schistosome intermediate hosts, but such agents could be suitable as
      biocontrol agents. To date, the most promising results have been obtained from
      experimental introductions of competitive snail species, but this strategy still
      has its drawbacks under many environmental conditions and the development of a
      universal method of biological control for the intermediate hosts of schistosomes
      is still a long way off.

PMID- 15463353
TI  - Current concepts in stage-regulated gene expression in kinetoplastida.
AB  - The different physiological environments provided by the hosts probably generated
      a strong selective force for the evolution of differential expression of gene
      products in digenetic kinetoplastid parasites. Indeed, the sorts of molecules
      that would be predicted to be stage-regulated have been found to be
      differentially expressed. Examples include transport molecules, metabolic
      enzymes, molecules involved in cell adhesion and penetration, and molecules
      involved in evasion of host defence mechanisms. Within the life cycle,
      environmental cues provided by the host, such as temperature and nutrients, may
      also function as triggers for the differential expression of gene products.

PMID- 15463354
TI  - Trypanosomatid transfection: stable introduction of DNA into protozoa.

PMID- 15463355
TI  - Sequestration in Plasmodium falciparum malaria: sticky cells and sticky problems.
AB  - Plasmodium falciparum is unique among the human malarias in displaying the
      phenomenon of sequestration, in which mature infected erythrocytes adhere to post
      capillary and capillary venular endothelium. In this review, Tony Berendt, David
      Ferguson and Chris Newbold describe the molecular and cellular biology of
      sequestration and cytoadherence. Potential host receptors identified to date that
      are expressed on endothelial cells (CD36, thrombospondin and ICAM-1) and the
      parasite-mediated changes in the infected erythrocyte (knob formation, senescence
      and the expression of parasite-derived neoantigens) are considered as well as the
      relevance of sequestration as a virulence factor in human disease and its
      potential role in parasite biology.

PMID- 15463356
TI  - DNA-binding antibodies and parasitic diseases.
AB  - DNA-binding antibodies are produced during the course of many parasitic
      infections, including malaria, leprosy and schistosomiasis. These antibodies are
      also present in certain autoimmune diseases, such as systemic lupus
      erythematosus, and much information is available about their properties and
      contribution to related disease processes Here, Anne Wozencraft and Norman
      Staines consider how DNA-binding antibodies might arise during parasitic
      infection and discuss how an increased knowledge of their properties and
      functions could lead to a greater understanding of mechanisms of immuno-pathology
      in these diseases.

PMID- 15463357
TI  - SLE and malaria: another look at an old idea.
AB  - An alternative view of the relationship between autoimmune disease and malaria is
      provided in the following article by Geoff Butcher and Ian Clark. Here they
      reassess the evidence that favours an earlier suggestion that where parasitic
      infections are common, autoimmune disease is rare. They suggest that malaria may
      exert a protective effect against the autoimmune nephritis in systemic lupus
      erythematosus (SLE).

PMID- 15463358
TI  - Mechanisms underlying immunosuppression induced by Trypanosoma cruzi.
AB  - Trypansoma cruzi affects immune responsiveness in mammalian hosts. Studies with
      patients and infected animals have defined some of the immunological dysfunctions
      but not the underlying mechanisms. Recent work using an in vitro model system of
      T. cruzi-human lymphocyte interactions has made it possible to uncover specific
      alterations in human lymphocyte activation induced by this parasite. Felipe
      Kierzenbaum and Marcelo Sztein discuss recent advances in our understanding of
      the processes that lead to impaired human lymphocyte function and that might be
      involved in the immunosuppression seen in the acute phase of Chagas disease.

PMID- 15463359
TI  - The ecology of lizard malaria.
AB  - The lizard malarias are a taxonomically and ecologically diverse group of
      parasites that offer excellent models for research on the ecology of malaria in
      free-ranging non-human vertebrate hosts. Studies over the past decade show that
      plasmodia of lizards can play an important role in the ecology and behavior of
      their hosts. The behavior of malarial infections in lizards also reveals
      unsuspected variation in the life history of Plasmodium.

PMID- 15463361
TI  - Schistosome surface protein anchors.

PMID- 15463360
TI  - Cysteine proteinases of parasitic protozoa.
AB  - Proteinases are involved with many processes in living organisms. In recent
      years, there has been increasing interest in elucidating the functions the
      enzymes perform in parasites. These studies have revealed that one class of
      proteinases, the cysteine proteinases, predominates in many parasitic protozoa.
      In this article Mick North, Jeremy Mottram and Graham Coombs review what is known
      about the cysteine proteinases of parasitic protozoa and discuss the approaches
      being pursued in attempts to design antiparasite drugs based on inhibitors or
      substrates of these enzymes.

PMID- 15463362
TI  - Insecticide resistance.

PMID- 15463363
TI  - Are wormy people parasite prone or just unlucky?

PMID- 15463364
TI  - Regulatory peptides in parasitic platyhelminths.
AB  - Regulatory peptides are short chains of amino acids that regulate cell-to-cell
      interactions in widely divergent animal groups. Evidence is accumulating to
      suggest that they mediate many aspects of physiology and behaviour, serving as
      neurotransmitters, neuromodulators and hormones. While most data in this field
      derive from studies on the mammalian nervous and endocrine systems, the last
      decade has witnessed an upsurge of interest in invertebrate peptide biology, not
      least because it is likely that many regulatory peptides originated in the
      nervous system of invertebrates. Platyhelminths, like other invertebrate groups
      investigated, contain numerous neuropeptides, and here David Halton and
      colleagues review the evidence that these putative signalling agents serve key
      roles in parasite motility, reproduction and morphogenesis. The physicochemical
      differences between host and parasite peptides raise the possibility that
      selective disruption of peptidergic control systems in parasites could be an
      exploitable target in future chemotherapeutic strategies.

PMID- 15463365
TI  - The chemical control of livestock parasites: problems and alternatives.
AB  - Over 200 classes of chemical compounds are currently in use for the treatment of
      livestock parasites. Here Les Strong and Richard Wall review some of the problems
      arising from the total reliance on chemical control and consider some of the
      alternative methods that might be given more thought and application.

PMID- 15463366
TI  - Single sex schistosomes and chemical messengers.

PMID- 15463368
TI  - Male schistosomes: more than just muscle?

PMID- 15463370
TI  - The new trypanosomatid genetics.
AB  - The recent development of transfection systems for trypanosomatids has removed a
      major obstacle to research and provides an important tool for the biochemist,
      immunologist and molecular biologist. Obtaining expression of a foreign gene in a
      trypanosomatid has been difficult. In this review, Vivian Bellofatto describes
      the problems and pitfalls of the process and final successes achieved.

PMID- 15463371
TI  - The role of nitrogen oxides as effector molecules of parasite killing.
AB  - The many years of effort in the attempt to identify the effector molecules of
      lymphokineactivated macrophages have recently come to fruition with the discovery
      of immuneactive nitrogen oxide. Here, Stephanie James and John Hibbs discuss the
      novel mammalian biochemical pathways for the synthesis of inorganic nitrogen
      oxides that mediate antibody-independent killing of infectious agents as well as
      of tumor cells. Interaction with nitrogen oxides causes iron loss from critical
      target enzymes in invading organisms, resulting in metabolic failure of
      extracellular and even of intracellular parasites of the macrophages themselves.

PMID- 15463372
TI  - Confocal scanning laser microscopy and helminth neuroanatomy.

PMID- 15463373
TI  - Memorable responses.

PMID- 15463374
TI  - Mathematical models for nematode parasites of ruminants.

PMID- 15463375
TI  - The immune recognition of malaria antigens.
AB  - Owing to the demonstration that the immune response of inbred mice to some
      defined malaria antigens is influenced by the major histocompatibility complex
      (MHC), and the finding that only a minority of individuals living in malaria
      endemic areas appear to recognize such antigens, there are fears that synthetic
      subunit malaria vaccines will be poorly immunogenic in a substantial proportion
      of the target population. Such fears have been reinforced by the results of the
      first two human malaria vaccine trials. In this review Eleanor Riley, Olle Olerup
      and Marita Troye-Blomberg summarize the experimental evidence for MHC-related
      genetic restriction of malaria immunity and discuss some alternative explanations
      for nonresponsiveness in populations living in malaria-endemic areas.

PMID- 15463376
TI  - Nematode collagen genes.
AB  - The collagen genes of nematodes encode proteins that have a diverse range of
      functions. Among their most abundant products are the cuticular collagens, which
      include about 80% of the proteins present in the nematode cuticle. The structures
      of these collagens have been found to be strikingly similar in the free-living
      and parasitic nematode species studied so far, and the genes that encode them
      appear to constitute a large multigene family whose expression is subject to
      developmental regulation. Collagen genes that may have a role in cell-cell
      interactions and collagen genes that correspond to the vertebrate type IV
      collagen genes have also been identified and studied in nematodes.

PMID- 15463377
TI  - The immune dependence of chemotherapy.
AB  - In this review, Mike Doenhoff and colleagues discuss the immune dependency of
      chemotherapy and the consequences for drug resistance. They also consider the
      implications for the control of infections that are relatively unresponsive to
      drugs, such as opportunistic infections in immunosuppressed patients.

PMID- 15463378
TI  - Triploidy in Paragonimus westermani.
AB  - The finding of triploid and diploid forms of Paragonimus westermani in Japan has
      caused tremendous controversy over the identity and speciation of this parasite.
      Should these two genetically different forms be given different specific names?
      Hirohiso Hirai and Takeshi Agatsuma have studied the lung flukes by using
      cytogenetic techniques and zymodeme analysis. In this article, they briefly
      compare triploid P. westermani with the diploid form and develop a hypothesis for
      the mechanism and origin of triploidy.

PMID- 15463379
TI  - The pathways of energy generation in filarial parasites.
AB  - It has been commonly accepted that most adult filarial parasites use the
      glycolytic breakdown of carbohydrates to lactate as a preferred route to supply
      their energy requirements. Their ability to catabolize glucose by oxygen
      dependent pathways is rather limited. An exception to this is the rodent filarial
      species Litomosoides carinii, which requires a unique type of aerobic glucose
      metabolism to maintain motor activity and survival. However, the prominent role
      of carbohydrates as energy substrates for filariids may no longer be tenable.
      Recent studies have shown that glutamine is a major energy source in filarial
      worms and that a fully oxidative mitochondrial metabolism can be employed for the
      utilization of this substrate.

PMID- 15463380
TI  - Erythrophagocytosis in malaria: Host defence or menace to the macrophage?
AB  - Macrophages in the host's bloodstream and tissue serve as a first line of defence
      during infection with Plasmodium. While the killing effect of these cells on
      parasites has been investigated extensively, relatively little is known about the
      phagocytosis of infected red blood cells. In this article, Paolo Arese and Franca
      Turrini have joined Hagai Ginsburg to address the perplexing relationships
      between the macrophage and the malaria-infected red blood cell. They suggest that
      the same molecular mechanisms that normally operate to remove senescent or
      damaged red blood cells also operate during malaria, although the parasite may
      indirectly cause the destruction of macrophages.

PMID- 15463382
TI  - Filarial worms: targets for drugs.

PMID- 15463381
TI  - Parasites and human T-cell subsets.

PMID- 15463383
TI  - Parasites and zoos.

PMID- 15463384
TI  - Host-related DNA sequences in the schistosome genome?

PMID- 15463385
TI  - Mosquito salivary glands: Parasitological and molecular aspects.
AB  - The salivary glands of mosquitoes serve in sugar feeding and blood vessel
      location. Components have been recently identified that may function in sugar
      feeding and digestion and platelet anti-aggregation. These factors correlate with
      salivary gland structure and appear to be controlled differentially in female
      mosquitoes. Analysis of gene expression has led to the discovery of three novel
      moieties in saliva: two involved in sugar feeding and one, specific to female
      mosquitoes, which is probably involved in blood feeding. Studies of parasite
      involvement in the salivary glands and host haemostasts have shown that parasites
      target specific interactions and modify them to enhance transmission. Here,
      Anthony James and Philippe Rossignol present an overview of mosquito salivary
      gland morphology and function, discuss recent advances in salivary gland
      molecular biology that have led to the discovery of new components and describe
      how parasites may modify salivary function to enhance transmission,.

PMID- 15463386
TI  - Immunological tolerance: The key feature in human filariasis?
AB  - Filariasis is a widespread tropical disease caused by a group of nematode
      parasites that can survive for many years in immunocompetent hosts. The paradox
      of filariasis has always been the inverse association between parasite density,
      in terms of circulating microfilariae in the blood, and severe pathology. In this
      review, Rick Maizels and Rachel Lawrence argue that microfilariae and adult
      parasites induce a form of immunological tolerance which prevents both parasite
      elimination and progression to disease. The breakdown of this unresponsiveness is
      seen as the critical step towards pathogenesis. However, not every exposed
      individual progresses through infection to disease. The authors discuss evidence
      for protective immunity acting on antigens from the mosquito-borne infective
      larva, and propose that this stage represents a vulnerable target outside the
      scope of tolerance and pathogenesis. Stage-specific larval antigens, to which
      asymptomatic hosts are known to respond, may therefore represent the most
      effective and safe choice for an anti filarial vaccine.

PMID- 15463388
TI  - Viruses of parasitic protozoa.

PMID- 15463389
TI  - Why do some African children develop severe malaria?
AB  - Malaria is still a major cause of death and severe illness among children in many
      parts of tropical Africa, but only a small proportion of children, perhaps 1-2%,
      who become ill with malaria develop severe disease. Why only, some children
      experience a severe or fatal attack is not understood clearly. In this article,
      Brian Greenwood, Kevin Marsh and Robert Snow review some of those characteristics
      of the parasite and the host that may influence the outcome of a malaria
      infection. Identification of the relative importance of the many factors likely
      to be involved is needed in order to develop rational strategies for the
      prevention of deaths from malaria among children in malaria-endemic areas.

PMID- 15463390
TI  - Site-specific retrotransposons of the trypanosomatid protozoa.
AB  - Retrotransposons are mobile genetic elements that have invaded a wide variety of
      organisms. While these mobile elements share gene homologies and structural
      features with retroviruses, they have lost the ability to produce infectious
      particles. Typically these elements are 5-10 kilobases (kb) in length, are
      conserved in their structural organization and are present in many copies in the
      genomes into which they have integrated(1). Retrotransposons generally interrupt
      their host genome promiscuously and thus cause a variety of random effects. In
      general, their insertion results in mutations, inversions, deletions or
      rearrangements among host sequences. All of these changes are thought to add to
      the plasticity of the host genome and thus contribute to a faster pace of
      evolutionary development. However, because of the random nature of insertions, it
      has been difficult to attribute any one specific function to these diverse
      elements. Here, Serap Aksoy describes a newly recognized family of mobile
      elements that are different from most retrotransposons in that they have the
      ability to integrate into specific host sequences.

PMID- 15463391
TI  - Regulation of gene expression in parasitic flatworms.
AB  - Transcriptional regulation and the role of transcription factors are widely
      regarded to be the major contributors controlling gene expression in eucaryotes.
      Translational control is less well understood due to the complexity of the
      components involved in regulation of protein synthesis at this level.
      Nevertheless, considerable advances have been made recently in elucidating the
      major controlling factors within the messenger RNA (mRNA) sequence and the
      translation machinery. In this article, Ron Podesta and Afzal Siddiqui suggest
      that protein synthesis in flatworm parasites is controlled post-transcriptionally
      and that these intracellular regulatory mechanisms are activated/suppressed by
      effectors of the host's immune response.

PMID- 15463392
TI  - Control of tsetse flies and trypanosomiasis: Myth or reality?
AB  - The African trypanosomiasis are among Africa's most devastating diseases. The
      human disease, sleeping sickness, and the animal disease, nagana, are caused by
      trypanosomes, protozoan parasites transmitted by tsetse flies, Glossina spp.
      Attempts have been made to control tsetse and trypanosomiasis for over 70 years,
      supported by ever-increasing amounts of foreign aid. Although progress has been
      made in the control of sleeping sickness, this disease still persists in many
      countries. Nogono excludes cattle from many of the potentially most productive
      areas of Africa and is a major constraint on economic development. In this paper,
      Robert Dransfield, Brian Williams and Robert Brightwell review the control of
      tsetse and trypanosomiasis in the light of recent progress in our understanding
      of tsetse population dynamics, with special reference to the experience gained in
      tsetse control on a Maasai ranch at Ngurumon in the Rift Valley of Kenya, and
      make suggestions for the management and funding of future control programmes in
      relation to rural development.

PMID- 15463393
TI  - Iron in the cell.

PMID- 15463394
TI  - The evolution of virulence: experimental evidence.

PMID- 15463395
TI  - The development and spread of drug-resistant malaria.
AB  - Resistance of Plasmodium falciparum to chloroquine has emerged in the late 1950s
      and has now conquered the large majority of areas where this species is endemic.
      Resistance to alternative drugs has already occurred in several parts of the
      world and has become a particularly serious problem in Thailand. Emergence and
      spread of resistance are the result of interactions between parasite, humans,
      vector and drugs, enhanced by particular ecological features. The control of
      malaria transmission by means other than drugs would probably curb the
      propagation of resistance but current health care policies offer only limited
      prospects for the reactivation or implementation of systematic malaria control
      before the potential of the affordable antimalarials has been exhausted. In this
      article, Walther Wernsdorfer considers the epidemiological factors associated
      with the development and spread of drug-resistant malaria.

PMID- 15463396
TI  - Schistosome female reproductive development.
AB  - Schistosome parasites have evolved to produce a number of unique features in
      their life history; one of these is separate sexes. This has, in turn, led to a
      novel interplay between the male and female parasite that has been recognized for
      over 50 years: the growth and reproductive development of the female parasite is
      in some way regulated by the male schistosome. Early classical and later
      experimental studies established that the presence of the male schistosome is
      necessary not only for the initiation of female development but also for the
      maintenance of her mature state. The male parasite regulates the reproductive
      development of the female, partly by providing a stimulus that is necessary for
      the development of the vitelline gland. The cells of the vitelline gland provide
      nutrients and shell precursors for the egg. Also in this review by Philip LoVerde
      and Li-ly Chen, it is interesting to note that recent molecular studies have
      confirmed early work by showing that gene expression in the female parasite is
      developmentally regulated in a tissue-specific manner and that this gene
      expression is controlled by the presence of a male parasite.

PMID- 15463398
TI  - Spherical bodies.

PMID- 15463399
TI  - BSP malaria meeting.

PMID- 15463400
TI  - Pyronaridine: A new antimalarial drug.
AB  - The worldwide spread of strains of Plasmodium falciparum that are resistant to
      chloroquine has highlighted the urgent need for new antimalarial drugs,
      particularly in less developed tropical countries. However, in the current
      economic climate the pharmaceutical giants in the developed world are withdrawing
      from tropical disease research. Consequently, the following article from Fu Sui
      and Xiao Shuhuo is of particular interest, not only because it summarizes work on
      on alternative antimalarial drug that is efficacious against multiply resistant
      Plasmodium but also because this drug has been developed primarily from Chinese
      research efforts, the results of which have largely only been published in the
      Chinese scientific literature. The drug under scrutiny is pyronaridine, and is
      the product of 30 years of chemistry that began with the mepacrine nucleus. This
      nucleus was selected as the starting point in the search for a chloroquine
      alternative because the various derivatives synthesized were active against
      chloroquine-resistant parasites. However, mepacrine itself also needed replacing
      as it is too toxic for mass use. After synthesizing and screening a huge series
      of substitutions, the addition of an amodiaquine side-chain to this nucleus was
      found to give the greatest activity for fewest adverse effects. Being aware of
      the rapid selection of pyronaridine-resistant Plasmodium strains that occurs in
      the laboratory, the Chinese efforts have also investigated the use of drug
      combinations to circumvent or delay the development of drug resistance. In
      addition to the triple combination described here, pyronaridine and primaquine
      combinations are under trial against both P. vivax and P. falciparum.
      Pyronaridine is a highly active blood schizonticide like chloroquine and
      amodiaquine. It has already undergone extensive trials in humans against both P.
      falciparum and P. vivax. However, nothing is known of its mode of action, nor the
      basis for the development of resistance and although it is active against
      chloroquine-resistant strains of parasite, paradoxically, pyronaridine-resistant
      Plasmodium is resistant to chloroquine.

PMID- 15463401
TI  - Helper T-cell subsets in mouse trichuriasis.
AB  - The fate of a primary infection with the nematode parasite Trichuris muris varies
      between different inbred strains of mouse. Most strains are resistant to
      infection, expelling the parasite before the adult worms develop. However, a few
      strains are unable to mount a protective immune response and will harbour chronic
      infections. Mouse trichuriasis thus provides on excellent helminth model in which
      to dissect the mechanisms of immunity operating during acute versus chronic
      infection. Here, Kathryn Else and Richard Grencis describe their recent work on
      the polarization of the helper T-cell response during infection with T. muris
      giving predominantly T(H)2-type cells in resistant strains of mouse and
      predominantly T(H)1-type cells in strains of mouse unable to expel the parasite.
      They also discuss their findings in relation to polarized helper T-cell responses
      reported for other intestinal nematodes.

PMID- 15463402
TI  - Parasite prevalence and host sample size.
AB  - Parasite prevalence is a summary statistic familiar to biologists. However, that
      there is an interspecific relationship between prevalence and sample size (the
      number of host individuals examined for parasites) is not widely appreciated. In
      this article, Richard Gregory and Tim Blackburn present some examples of this
      negative relationship, explain the mechanisms that underlie this pattern and
      discuss the potential problems this association might create for biological
      studies.

PMID- 15463403
TI  - A model for the dynamics of human lymphatic filariasis.
AB  - In this paper, Bryan Gren fell, Edwin Michael and David Denham review the
      appropriateness of feline filariasis as a model of the population dynamics of
      human lymphatic filarial infection and disease. Because of the longevity of
      infection and our inability to measure the adult parasite population in humans,
      research in filariasis is particularly dependent on the use of laboratory animal
      models. We demonstrate that Brugia pahangi infection patterns in the cat closely
      parallel those of Brugia and Wuchereria in humans. Although primary infections in
      'susceptible' cats are long-lived, repeatedly infected animals show evidence of
      concomitant immunity which prevents the establishment of later cohorts of
      infective larvae. Furthermore, there is some evidence from macro filarial length
      distributions of 'stunting' of adult worms during long-term repeat infections.
      Cats can also show an 'acute' response that spontaneously eliminates infections,
      and this appears to be due to a combination of intrinsic and dynamic mechanisms.
      As in humans, pathology in cat filariasis develops as a sequel to the
      asymptomatic microfilaremic state, largely as a result of re-expression of
      immunity. The relationship between macro filarial burdens and microfilariae in
      blood is positive but portrays a high degree of variability. The cat model
      provides an important tool for elucidating the relationships between infection,
      immunity and disease dynamics in lymphatic filariasis, and we conclude by
      suggesting directions for further work in this area.

PMID- 15463404
TI  - Limited tolerance.

PMID- 15463405
TI  - The Bancroft Centre: a tradition continued.

PMID- 15463406
TI  - Proposal for a uniform genetic nomenclature in Toxoplasma gondii.

PMID- 15463407
TI  - The influence of parasites on host sexual selection.
AB  - In 1982 Hamilton and Zuk(1) proposed a provocative solution for the unexplained
      fact that the males of many species exhibit 'showy' traits such as brightly
      coloured plumage or vigorous courtship displays. They suggested that showy traits
      are fully expressed only by males who are resistant to parasites and that females
      examine such traits in order to choose resistant males as mates. Hamilton and
      Zuk's proposal has been the topic of extensive research and vigorous debate for
      nearly a decade. This article reviews the research, relevant criticisms and
      unanswered questions pertaining to the influence of parasites on sexual
      selection.

PMID- 15463408
TI  - Phagolysosomal escape by intracellular pathogens.
AB  - It has often been suggested that intracellular parasites invade cells in order to
      evade the host's immune response. Whether or not this view is correct, have
      successfully avoided excessive scrutiny by biomedical investigators. Published
      descriptions of the intracellular compartments occupied by parasites often
      contradict each other, reflecting the fact that the early events following host
      cell invasion remained, until recently, poorly understood. In this review, Norma
      Andrews and Paul Webster focus on what is now known about a dramatic transition
      that some parasites undergo after invading cells: escape from a membrane-bound
      vacuole into the cytosol. They discuss the information available on strategies
      for phagolysosomal escape of pathogens ranging from bacteria to protozoa, with
      emphasis on the cases in which the molecular mechanisms controlling this event
      have been investigated.

PMID- 15463410
TI  - Rodent malaria models.

PMID- 15463411
TI  - The endemic normal in lymphatic filariasis: A static concept.
AB  - Residents of areas endemic for lymphatic filariasis are continually exposed to
      infection with mosquito-transmitted infective larvae (L3), some of which survive
      to become adult worms and subsequently produce micro filarial (mf) transmission
      stages. The question of whether naturally acquired resistance occurs in adult
      residents of endemic areas has recently become of interest as the development of
      molecular vaccines against filarial parasites is being considered(1,2). There
      have been two epidemiological approaches to demonstrate acquired resistance to
      Filariasis in human populations. In this review Karen Day examines both
      approaches in the context of an immunoepidemiological study of bancroftian
      filariasis in Papua New Guinea (PNG). The merits of each as a conceptual
      framework for studies of protective immunity in lymphatic filariasis will be
      discussed.

PMID- 15463412
TI  - Development of a genetically engineered vaccine against poultry coccidiosis.
AB  - Coccidiosis is caused by infection with Eimeria spp. The disease is responsible
      for major economic loss to the poultry industry unless infections are controlled
      by anticoccidial drugs. John Ellis and Fiona Tomley discuss recent research on
      the characterization and cloning of antigens from Eimeria spp and advances
      towards the development of genetically engineered vaccines against poultry
      coccidiosis.

PMID- 15463413
TI  - Vaccines against gastrointestinal nematode parasites of ruminants.
AB  - A consequence of intensive livestock production is an increase in the incidence
      and impact of gastrointestinal (GI) parasites. Farmers have sought to redress
      this shift in the natural host-parasite relationship by chemotherapy. However,
      with the widespread development of resistance to anthelmintics and the current
      impetus for sustainable agricultural practices, alternatives such as vaccines are
      being sought to maintain animal productivity. In this article, David Emery and
      Barry Wagland discuss recent advances in immunity to nematode infections of
      ruminants and the development of vaccines made possible by the dogged persistence
      and ingenuity of cadres of parasitologists who have done more than 'go through
      the motions'.

PMID- 15463414
TI  - Chronotherapy of malaria: an approach to malaria chemotherapy.
AB  - Chronotherapy is the science of the timing of drug application so as to achieve
      optimal therapeutic success for the treatment of disease. Here, Irene Landau,
      Alain Chabaud, Gilles Cambie and Hagai Ginsburg show how a suitable animal model
      can be chosen, how the stage of parasite development most susceptible to the drug
      can be identified, and how this can eventually be used for the improvement of
      drug treatment.

PMID- 15463416
TI  - Ticks: Vectors and vaccines.

PMID- 15463415
TI  - Mammalian immune responses to myiasis.
AB  - Myiasis is responsible for significant losses to the livestock industry
      worldwide. Control programs have been successful in reducing the number of
      infested animals. However, serious concerns regarding the use of pesticides have
      prompted research into alternative strategies for pest control. In this article,
      Bob Baron and Doug Colwell discuss progress made towards the understanding of the
      immune response to Hypoderma spp and other myiasis-producing arthropods.
      Prospects for vaccination are discussed.

PMID- 15463418
TI  - Social and economic research in TDR: future directions.

PMID- 15463417
TI  - Parasite neurobiology.

PMID- 15463419
TI  - The epidemiology of lyme borreliosis.
AB  - The tick-transmitted bacterial infection known as Lyme disease, or Lyme
      borreliosis, has recently emerged as the leading arthropod-borne disease in
      Europe and North America. Several thousand new cases of human Lyme disease are
      reported each year from Europe and the USA. The causative agent, Borrelia
      burgdorferi, has been isolated from several species of mammals, birds, ticks and
      insects and, in this article, Thomas Jaenson discusses the geographical
      differences in the epidemiology of the infection.

PMID- 15463420
TI  - Hydatid disease in China.
AB  - Hydatid disease is one of the world's most geographically widespread zoonoses. It
      is present on all inhabited continents and occurs in tropical, subtropical,
      temperate, sub-arctic and arctic regions. The two countries with the greatest
      areas over which transmission occurs are almost certainly the Soviet Union and
      China. Until recently, however, very little information about hydatidosis in
      China was available outside the country(1). Since the 'open-door' policy over the
      past few years the great importance of hydatid disease in north and western China
      is gradually being realized.

PMID- 15463421
TI  - Vertical transmission of helminths: Hypobiosis and amphiparatenesis.
AB  - Vertical transmission has evolved in at least five lines of helminths and
      involves prenatal or, more commonly, transmammary pathways to the offspring. In
      this article, vertical transmission, hypobiosis and paratenesis are combined in a
      strategy for transmission called amphiparatenesis. Although many believe that
      vertical transmission of parasites is rare, Wesley Shoop suggests that it is not
      only significant in the evolution of certain helminths but it may have been one
      of the pivotal adaptations in the evolution of the eukaryotes and is essential in
      their continued existence.

PMID- 15463422
TI  - The epidemiology and economic impact of llama parasites.
AB  - Camelids are distributed over vast areas of South America, ranging from south
      Ecuador to north Chile, with high concentrations in Peru and Bolivia. Guillermo
      Leguio discusses the effects that parasitic infections have on the health and
      productivity of these animals.

PMID- 15463423
TI  - The functional and immunological significance of some schistosome surface
      molecules.
AB  - The molecules discussed in this review include some of the leading vaccine
      candidates in schistosomiasis: the glutathione S-transferases, triose-phosphate
      isomerase, glyceraldehyde-3-phosphate dehydrogenase and the 23 and 25 kDa surface
      integral membrane proteins. Mark Wright, Kathy Davem and Graham Mitchell
      highlight the possible biological roles and immunological relevance of these
      molecules.

PMID- 15463424
TI  - Unique roles for lipids in Schistosoma mansoni.
AB  - The dynamic interplay among lipids has been exploited by S. mansoni to evolve
      some unique processes that are vital for its long-term survival within the
      mammalian host. Lipids are required by the parasite not only to maintain its
      surface integrity and structural requirements but also for egg production and
      cell-cell signalling. However, S. mansoni is incapable of synthesizing essential
      lipids and must obtain these from its host. In this review, Stephen Furlong
      describes the roles and routes of acquisition o f lipids by this parasite.

PMID- 15463425
TI  - Urinary schistosomiasis and the coming of age in Nigeria.

PMID- 15463446
TI  - First impressions of the malaria vaccine.

PMID- 15463447
TI  - The P-glycoprotein homologues of Plasmodium falciparum: Are they involved in
      chloroquine resistance?
AB  - Chloroquine has been the mainstay of antimalarial chemotherapy but the rapid
      spread of resistance to this important drug has now compromised its efficacy. The
      mechanism of chloroquine resistance has not been known but recent evidence from
      Plasmodium falciparum, the causative agent of the most severe form of human
      malaria, suggested similarities to the multidrug resistance phenotype (MDR) of
      mammalian tumour cells which is mediated by a protein molecule termed P
      glycoprotein. Two mdr genes (pfmdr1 and pfmdr2) encoding P-glycoprotein
      homologues have been identified in P. falciparum and one of these (pfmdr1) has
      several alleles that have been linked to the chloroquine resistance phenotype. In
      contrast analysis of a genetic cross between chloroquine-resistant and -sensitive
      P. falciparum has suggested that the genes encoding the known P-glycoprotein
      homologues are not linked. This review outlines the similarities of the
      chloroquine resistance phenotype with the MDR phenotype of mammalian tumour cells
      and explores the possible role of the pfmdr genes.

PMID- 15463448
TI  - Viruses of parasitic protozoa.
AB  - Recently, specific viruses have been identified among the parasitic protozoa
      Trichomonas vaginalis, Giardia lamblia, Leishmania braziliensis, the Eimeria spp
      and the Babesia spp. These viruses share many features: they are all RNA viruses
      and most, if not all, doublestranded (ds) RNA viruses with nonsegmented genomes
      ranging between 5 and 7 kilobases (kb); they are spherical or icosahedral with an
      average diameter of 30-40 nm. The giardiavirus is one of the best characterized
      and can infect virus free G. lamblia trophozoites in its freed, pure form. The
      replicative intermediate of the giardiavirus genome has been isolated from
      infected cells, and can be introduced into G. lamblia by electroporation to
      produce giardiavirus, thus raising the possibility of its being used as a
      specific genetic transfection vector for the parasite.

PMID- 15463449
TI  - Recent contributions to new world archaeoparasitology.

PMID- 15463451
TI  - Cloning of schistosomes.

PMID- 15463452
TI  - Modulation of host cell metabolism by Trypanosoma cruzi.
AB  - Chagas disease, caused by the hemoflagellate Trypanosoma cruzi, is a complicated
      and devastating disease. It is hypothesized that an important target of infection
      may be the endothelial cell and that both the acute and chronic forms of the
      disease involve abnormalities in the microcirculation. Stephen Morris and
      colleagues suggest that endothelial cell dysfunction occurs as a consequence of
      amastigote-associated interference in host cell metabolism.

PMID- 15463453
TI  - Avian trypanosomes as models of hemoflagellate evolution.
AB  - In the 15 years since the last review on avian trypanosomes(1), there has been a
      steady accrual of information on the distribution and dynamics of trypanosome
      infections in wild bird populations. Recent immunological and biochemical studies
      provide evidence that several trypanosome species can parasitize an ecological
      guild of host species but the relative roles of avian host phylogeny and vector
      ecology remain unanswered. In this article, Victor Apanius reviews the habitat
      preferences and behavior of trypanosomes within the avian host and attempts to
      draw similarities in the strategy employed by the parasite for persistence in
      different vertebrate classes. Next, the question of host specificity is raised
      and recent evidence on the subject is examined with an eye toward understanding
      the distribution of trypanosome species in host communities.

PMID- 15463455
TI  - The puzzle of protist organelles.

PMID- 15463454
TI  - The use of antisense oligonucleotides as chemotherapeutic agents for parasites.
AB  - Although several approaches to the control of human parasites are possible, the
      prevention and therapy of the corresponding diseases still remain a difficult
      task. The development of vaccines has been hampered by the poor immunological
      response to or the high variability of parasitic antigens. Problems also arise
      for chemotherapy where differences in the biochemistry of host and parasite must
      be exploited. The increasingly difficult search for new drugs is always
      challenged by the appearance of resistance.

PMID- 15463456
TI  - Tropomyosin and molecular mimicry.

PMID- 15463457
TI  - Onchocerciasis control in Nigeria.

PMID- 15463458
TI  - On the function of repetitive domains in protein antigens of Plasmodium and other
      eukaryotic parasites.
AB  - Highly reiterated repetitive domains occur within the protein antigens of many
      parasitic taxa, including Plasmodium, Trypanosoma, Leishmania and Toxoplasma. In
      malaria it has been proposed that repeat regions may function as ligands for host
      proteins, or serve to suppress the development of immunity through a strategy of
      serological crossreactivity. In this article Louis Schofield presents a novel
      hypothesis, based on empirical evidence, that repetitive domains in antigens do
      not elicit protective immune responses and instead have evolved as a mechanism of
      immune evasion by their ability to induce thymus-independent B-cell activation.
      It is also proposed that this unusual response is associated with several forms
      of immunosuppression. The hypothesis has the added attraction of helping to
      explain several distinctive features of the molecular biology, evolution and
      immunology of repetitive regions in protein antigens of parasites.

PMID- 15463459
TI  - The evolutionary origin of glycosomes.
AB  - The glycolytic pathway of the Kinetoplastida is organized in a unique manner: the
      majority of its enzymes are contained in organelles called glycosomes. In this
      article Paul Michels and Fred Opperdoes argue that the glycosomes are equivalent
      to the microbodies and peroxisomes identified in other eukaryotic cells. They
      explore the possible evolutionary origin of the glycosome by comparing many of
      its structural and functional properties with those of other members of the
      microbody family and with some features of other organelles, the mitochondria and
      chloroplasts, which have been studied in much more detail.

PMID- 15463460
TI  - Molecular genetics of drug resistance in Plasmodium falciparum malaria.
AB  - Resistance to dihydro folate reductase inhibitors and resistance to chloroquine
      have been mapped to single genetic loci in Plasmodium falciparum. Specific point
      mutations in the dihydro folate reductase gene confer different degrees of
      resistance to two dihydro folate inhibitors, cycloguanil and pyrimethamine,
      depending on the positions of the mutations and the residues involved. The
      chloroquine resistance locus has been mapped to a 400 kilobase (kb) segment of
      chromosome 7 in a P. falciparum cross. Identification and characterization of
      genes within this segment should lead to an understanding of the rapid drug
      efflux mechanism responsible for chloroquine resistance.

PMID- 15463461
TI  - Organelles of protein transport in Giardia lamblia.
AB  - Giardia occupies a unique evolutionary position since it is considered to belong
      to the earliest known lineage to diverge from the eukaryotic line of descent.
      Although organelles of protein transport are thought to have evolved with the
      nuclear membrane, G. lamblia is reported to have no Golgi apparatus. Therefore,
      Frances Gillin, David Reiner and Michael McCaffery have investigated how it
      exports glycoproteins to the cyst wall during encystation and whether a Golgi
      might become evident during an active secretory phase. They have found both
      functional and morphological evidence of a Golgi in Giardia and have shown that
      trophozoites are capable of sophisticated protein recognition, sorting and
      trafficking. These studies suggest that membranous organelles of protein
      transport appeared early in the evolution of the eukaryotic cell.

PMID- 15463462
TI  - Do parasites express receptors for host lipoproteins?
AB  - Although cholesterol is the predominant sterol in parasite tissue, many parasites
      are unable to synthesize cholesterol or longchain fatty acids, de novo, and must
      therefore obtain these components from the host. Of particular interest are the
      plasma lipoproteins, a rich and abundant source of cholesterol, and other lipids
      that could be used by parasites inhabiting the vascular system of their host or
      with access to plasma proteins at extravascular sites. It is not inconceivable
      that parasites may have evolved a variety of receptors for lipoproteins by
      convergent evolution. Here, Mark Rogers discusses evidence for the presence of
      lipoprotein receptors in protozoan and metazoan parasites of mammals.

PMID- 15463463
TI  - Inter-individual variation in the metabolic activation of the antimalarial
      biguanides.
AB  - The aryl-biguanides proguanil and chlorproguanil were developed as part of a
      collaborative programme between ICI and the Liverpool School of Tropical Medicine
      during the 1940s. The compounds were characterized by their absence of host
      toxicity. However, the rapid development of parasite resistance to the actions of
      these drugs and the development of the 4-aminoquinoline, chloroquine, severely
      limited their use. The subsequent widespread development of parasite resistance
      to chloroquine, together with the observations that the magnitude of
      dihydrofolate reductase inhibitor resistance (the site of action of the
      biguanides) developed to pyrimethamine is not directly correlated with biguanide
      resistance(1,2). has resulted in renewed interest in these drugs. In particular,
      proguanil is now the drug of choice for malaria prophylaxis, in combination with
      chloroquine; used in combination with a suitable sulphonamide, it may be of value
      in malaria therapy.

PMID- 15463464
TI  - Memorable responses.

PMID- 15463467
TI  - Self-control.

PMID- 15463466
TI  - Biological control for freshwater snails.

PMID- 15463468
TI  - New insights into the structure of a Trypanosoma cruzi protease.

PMID- 15463469
TI  - Have malaria parasites three genomes?
AB  - Recent efforts to define the mitochondrial genome of malaria parasites have
      uncovered an unexpected complexity: there are two almost totally dissimilar
      organellar DNA molecules. lain Wilson, Malcolm Gardner, Jean Feagin and Donald
      Williamson discuss the surprising possibility that Plasmodium may have, in
      addition to the nuclear genome, two unrelated organellar genomes, one evidently
      mitochondrial and the other of unknown function.

PMID- 15463470
TI  - Rodent trypanosomes: their conflict with the immune system of the host.
AB  - Rodent trypanosome infections provide the opportunity to study major phenomena
      that are displayed in many parasite-host combinations and, therefore, the chance
      to contribute to the elucidation of those phenomena. Here, Julia and Joseph
      Albright focus on the immune responses to rodent trypanosomes and on the tricks
      the parasites play to minimize the effects of those responses.

PMID- 15463471
TI  - Immune-facilitated drug action.

PMID- 15463472
TI  - Sample size in parasitological and vector surveys.

PMID- 15463473
TI  - Cytopathogenic effect of Giardia intestinalis, in vitro.

PMID- 15463474
TI  - The survival of Plasmodium Under oxidant stress.
AB  - Oxidant stress is associated with the generation of reactive oxygen-derived
      species, which are considered as the ultimate agents responsible for the damage
      of a variety of cellular components. Transition metals such as iron ions serve as
      catalytic centers for the repeated conversion of superoxide radicals or ascorbate
      to the highly reactive and deleterious hydroxyl radicals and, indeed, increasing
      amounts of redox-active iron become available during plasmodial development
      within the parasitized erythrocytes. Thus, the survival of an intracellular
      parasite depends on the delicate balance of oxidant stress and defense
      mechanisms. This balance is continuously changing and the parasite must cope with
      increasing oxidant stress and the decline of protective capacity.

PMID- 15463475
TI  - Cloning of schistosomes.

PMID- 15463476
TI  - Transovarial transmission.
AB  - The success of a parasite depends upon its ability to transmit itself to new
      hosts. Many parasites are passed on from mother to daughter in a process known as
      vertical, or linear, transmission. Vertical transmission includes parasites
      transmitted across the placenta or via milk but in this review Judy Smith and
      Alison Dunn concentrate specifically on intracellular parasites. Transovarial
      transmission is widely used by a range of organisms but its importance,
      particularly in transmission of parasites, has rarely been studied.

PMID- 15463477
TI  - Comparison of genes encoding Trypanosoma cruzi antigens.
AB  - Trypanosoma cruzi, the causative agent of Chagas disease, simultaneously
      expresses several different surface antigens. This contrasts sharply with blood
      stream forms o f the African trypanosomes, which display only one variant surface
      glycoprotein at a time. Over the past few years, the genes coding for a number of
      T. cruzi proteins recognized by sera from patients have been cloned and at least
      partially sequenced. However, some of those discovered in more than one
      laboratory have been given different names. Here, Carlos Frasch, Juan Cazzulo,
      Lena Aslund and UIf Pettersson try to systematize the literature available on
      these antigens, including what is known about their localization and function.

PMID- 15463478
TI  - The discovery of Angiostrongylus cantonensis as a cause of human eosinophilic
      meningitis.
AB  - The theoretical and subsequent confirmation in 1961 of the rat lungworm,
      Angiostrongylus cantonensis, as the causative agent o f eosinophilic meningitis
      is one o f the remarkable parasitological findings of the twentieth century.
      Here, Joseph Alicato briefly summarizes the early history and his epidemiological
      studies on the relationship between the parasite and the epidemics o f
      encephalitis that swept through Oceania after the Second World War.

PMID- 15463479
TI  - Cattle may more safely graze.

PMID- 15463480
TI  - Circular and linear multicopy DNAs in Leishmania.

PMID- 15463481
TI  - Immunity to the liver stage of malaria.
AB  - The search for subunit vaccines against malaria has concentrated on asexual and
      sexual blood stage and sporozoite antigens. In recent years the search for the
      basis of the protection against sporozoite challenge obtained in mice immunized
      with irradiated sporozoites has focused attention on the liver or exoerythrocytic
      (EE) stage of the malaria life cycle. Here, Andreas Suhrbier looks at the various
      immune responses that appear to be active against this stage, which was once
      thought to be immunologically insignificant. The liver stage of malaria has thus
      emerged as a legitimate target for vaccine development.

PMID- 15463483
TI  - Malaria vaccine.

PMID- 15463482
TI  - The interaction between intestinal mucus glycoproteins and enteric infections.
AB  - Adherence of pathogenic enteric organisms to specific receptors on mucosal
      surfaces is widely recognized as an important first step in the initiation of
      infectious diseases. The specific interactions whereby parasites and bacteria
      exploit mucus substrates for colonization, and the host uses them as a
      nonimmunological defense mechanism, is only now being unravelled. In this review,
      Sil-King Tse and Kris Chadee discuss various hypothetical models for interaction,
      including the role of the immune system in the regulation of mucus secretion.

PMID- 15463484
TI  - Culture, in vitro, of nematodes of veterinary importance.

PMID- 15463485
TI  - Cell surface proteins of Entamoeba histolytica.
AB  - To ask what is new in Entamoeba histolytica research, one need look no further
      than the surface of this protozoan parasite. In the past year the cloning and
      partial characterization of five different surface antigens have been reported, a
      remarkable result of international research efforts against amebiosis. One of
      these proteins is the first protective immunogen identified in the animal model
      of amebic liver abscess. Barbara Mann and William Petri review these recent
      results, propose a nomenclature for the gene family of E. histolytica galactose
      lectins and discuss the roles of the different surface proteins in adhesion.

PMID- 15463486
TI  - Etymology of loa.

PMID- 15463487
TI  - Heligmosomoides polygyrus or Nematospiroides dubius?
AB  - The intestinal trichostrongylid nematode of mice, Heligmosomoides polygyrus
      bakeri, is often referred to as Nematospiroides dubius. Here, Jerzy Behnke, Anne
      Keymer and John Lewis ask the question: which is correct?

PMID- 15463488
TI  - Critical stages in the development of Plasmodium in mosquitoes.
AB  - One tool for the control of malaria that may become available to future
      generations of public health workers is the introduction of genes into the
      Anopheline vector populations that will render the mosquitoes refractory to
      Plasmodium. Insights from basic research that could transform this idea into a
      technical reality are presently lacking. In this review, Alon Warburg and Louis
      Miller focus on one crucial area of research: the identification of potentially
      vulnerable points in the developmental cycle of Plasmodium in mosquitoes.

PMID- 15463489
TI  - Parasites as biological tags.
AB  - Parasites suffer from bad public relations. In The Goodness of Parasitism: A New
      Hypothesis, Lincicome proclaimed 'Parasitism, one of life's great phenomena,
      possesses a quality of goodness that has largely been overlooked because man has
      been so possessed with the disease aspects of this association'. It has been
      twenty years since Lincicome led the call for parasites' acceptance as admirable
      organisms, apparently without much success. Here, Mike Moser offers a brief
      reminder of the virtues of parasites and the benefits of being parasitized.

PMID- 15463490
TI  - Malaria vaccines: While we are waiting.

PMID- 15463491
TI  - Pf155/RESA is not a surface antigen of Plasmodium falciparum-infected
      erythrocytes.

PMID- 15463492
TI  - Chemotherapy of filariases.
AB  - The filarial parasites that affect humans most seriously include Onchocerca
      volvulus, Wuchereria bancrofti, Brugia malayi and Loa loa. In general, these
      species cause disease that is debilitating long before it is fatal, producing
      clinical manifestations such as general malaise, pruritus and lichenification of
      the skin, lymphangitis, elephantiasis and blindness(1). As a result, infection
      with any one of these organisms is physically, as well as economically,
      devastating. Currently, the pharmacological armamentarium with which to treat
      filarial infections is very limited and many of the drugs that are known to be
      efficacious against these worms may produce side effects that cause extreme
      discomfort. Here, Elizabeth Vande Waa describes the quest for new
      chemotherapeutic approaches for the treatment of filarial infections.

PMID- 15463493
TI  - Plasmodium sexual stage antigens.
AB  - The sexual stages of the malaria parasite are highly specialized cells adapted to
      withstand major environmental changes during their development. They also induce
      immune responses that may affect the outcome of the infection in the mosquito. In
      this review Pietro Alano considers the nature and the role of the antigens
      expressed by Plasmodium sexual stages.

PMID- 15463494
TI  - Cloning of schistosomes.

PMID- 15463496
TI  - Role of lipids in Schistosoma mansoni.

PMID- 15463497
TI  - Proposed link between cytokines, nitric oxide and human cerebral malaria.
AB  - Nitric oxide (NO), also known as endothelial-derived relaxing factor (EDRF), is
      generated by a range of cell types including endothelial cells, smooth muscle
      cells and neurons, and mediates a range of different physiological functions,
      such as maintenance of vascular tone and neuro-transmission. In this article, Ian
      Clark, Kirk Rockett and Bill Cowden propose that when vascular generation of NO
      is particularly high (for example, if local intravascular levels of tumour
      necrosis factor (TNF) are markedly increased) this mediator could diffuse to
      nearby neurons, be misinterpreted as being of synaptic origin and thus interfere
      with orderly neuro-transmission. NO of vascular origin could also, through
      vasodilation of cerebral vessels, contribute to increased intracranial pressure
      and thus to certain of the clinical signs seen in cerebral malaria. As well as
      contributing to cerebral malaria, these phenomena could also lead to the
      neurological changes observed in certain other systemic diseases.

PMID- 15463498
TI  - The dynamics of antigenic variation and growth of African trypanosomes.
AB  - Antigenic variation in African trypanosomes, which is a simple strategy for
      survival in the immune host, is rendered complex by its magnitude. For protection
      from nonspecific immunity and escape from specific immunity, each trypanosome is
      covered by a replaceable surface coat composed of the variant surface
      glycoprotein (VSG), which specifies the variable antigen type (VAT) of the
      trypanosome. Antigenic variation is the process by which the trypanosome switches
      from one coat to another. Here, David Barry and Michael Turner consider this
      phenomenon within the context of the course of trypanosome infection.

PMID- 15463499
TI  - The structure and role of RNA polymerases in Plasmodium.
AB  - During the past few years the characterization of several Plasmodium falciparum
      RNA polymerase subunits has revealed potentially significant differences between
      the corresponding subunits of the host and parasite enzymes(1-3). The largest
      subunits of P. falciparum RNA polymerase II and III contain enlarged variable
      domains that separate conserved domains in these subunits. The partially
      characterized beta and beta '-like subunits of an organellar P. falciparum RNA
      polymerase also appear to be distinct from the host RNA polymerases. In this
      review David Bzik discusses the structure and role of RNA polymerases in
      Plasmodium.

PMID- 15463500
TI  - Application of 3-d computer-aided reconstruction in parasitology.
AB  - Three-dimensional (3-D) reconstruction is sometimes useful to describe the fine
      morphology of the subcellular organization of parasites. Francois Polluoult,
      Bruno Pietrzyk, Eduardo Dei-Cas and Daniel Camus show how computer-aided
      reconstruction from serial sections is done.

PMID- 15463502
TI  - Vector control: making predictions.

PMID- 15463501
TI  - Potential of microsporidia for the biological control of mosquitoes.
AB  - The use of larvicides for the control of disease vector mosquitoes is not always
      practical. Tony Sweeney and Jimmy Becnel discuss prospects for the use of
      microsporidio, particularly Edhazardia aedis, as biocontrol agents.

PMID- 15463503
TI  - Rhoptry lipids and parasitophorous vacuole formation: a slippery issue.

PMID- 15463504
TI  - Towards a population genetics of microorganisms: The clonal theory of parasitic
      protozoa.
AB  - Over the past 15 years, molecular investigations, including the study of isozymes
      and DNA markers, have provided much information on the genetic variation,
      population structure, breeding system and other population characteristics of
      parasitic protozoa. For some parasitic protozoa, but not for others, the evidence
      indicates that their reproduction is prevailingly clonal. In this article, Michel
      Tibayrenc and Francisco Ayala propose that the issue of whether the predominant
      mode of reproduction of a given micro-organism is clonal or sexual can only be
      settled by population genetics information, and they summarize evidence favoring
      a clonal population structure for a number of parasitic protozoa.

PMID- 15463505
TI  - Malaria parasites: Randomly interbreeding or 'clonal' populations?
AB  - The 'clonality' hypothesis proposed by Michel Tibayrenc and his colleagues(1) has
      stimulated a long-overdue debate on the genetic structure of populations of
      protozoan parasites. A critical aspect of the hypothesis is the role of a sexual
      phase in the life cycle of these organisms. In the malaria parasite, Plasmodium,
      the existence of a sexual phase is unquestioned and is, indeed, a compulsory part
      of the cycle in the mosquito host. For this parasite, therefore, the principal
      question to be addressed, here by David Walliker, is whether populations of this
      parasite in nature are in a state of random mating (panmixia) or whether they
      comprise a limited number of clones which only occasionally undergo crossmating.

PMID- 15463506
TI  - Population genetics of nonclonal, nonrandomly mating malaria parasites.
AB  - In a highly controversial paper(1), Tibayrenc and colleagues have argued that
      clonal (asexual) reproduction may be a general phenomenon among protozoan
      parasites. Many parasitologists would be quite comfortable with a theory applied
      to Leishmania, Trypanosoma, Entamoeba and Giardia which proposes 'that
      uniparental reproduction is ... predominant enough in natural populations to
      generate clones that are stable in space and time ...' The current view is that
      these parasites can reproduce sexually some of the time (eg. Refs 2,3) but may
      not do so most of the time. What has provoked the most controversy(4-7) is the
      suggestion that malaria parasites can be considered as bedfellows of the above,
      for Plasmodium are generally thought to undergo obligate sexual reproduction in
      each generation. Here, Christopher Dye focuses on Tibayrenc's arguments for
      clonal reproduction in Plasmodium, not only because malaria parasites are at the
      heart of the dispute but also because an analysis of his arguments about sexually
      reproducing parasites carries implications for his assertions in general.

PMID- 15463507
TI  - Development and interactions of Trypanosoma cruzi within the insect vector.
AB  - Transmission of Chagas disease or American trypanosomiasis depends on Trypanosoma
      cruzi development and differentiation within its triatomine insect vector. In
      this review, Eloi Garcia and Patricia de Azambuja aim to outline the current
      areas of research that may explain aspects of the parasite-vector interaction.

PMID- 15463508
TI  - Morbidity, due to schistosomiasis mansoni, and its control in Subsaharan Africa.
AB  - The measuring and monitoring of morbidity are essential components of
      schistosomiasis control programmes. Bruno Gryseels and Anton Polderman assess the
      objectives, difficulties and importance of morbidity control of schistosomiasis
      mansoni in subsaharan Africa.

PMID- 15463510
TI  - Trypanosomes and tomatoes.

PMID- 15463512
TI  - BSP malaria meeting.

PMID- 15463511
TI  - Bovine sarcocystosis: How parasites negatively affect growth.
AB  - Growth, though genetically encoded, is markedly influenced in healthy animals by
      the interaction of hormonal and nutritional factors. The uptake and use of
      nutrients by specific tissues is regulated by a priority system that modulates
      physiological processes. Nutritional, hormonal and immunological consequences of
      parasitism often lead to partitioning of nutrients away from growth. In this
      article, Ron Foyer and Ted Elsosser use a bovine sarcocystosis model to show that
      changes in plasma concentrations of insulin-like growth factor-I (IGF-I), growth
      hormone (GH) and somotostotin (SSN), as well as the host's immunological response
      to the parasite via cytokine interactions with the endocrine system, are
      modulators of perturbed growth.

PMID- 15463513
TI  - Nucleic acid techniques and the detection of parasitic diseases.
AB  - The detection of infectious disease-causing organisms is important for the
      initiation of effective treatment, in monitoring response to therapy and in
      epidemiological studies of disease of human or animal hosts. In this article
      Stuart Wilson primarily considers parasitic diseases, but much can be applied to
      infectious diseases in general.

PMID- 15463514
TI  - Problems with oxygen.

PMID- 15463516
TI  - Cell cycle co-ordination in trypanosomes.

PMID- 15463515
TI  - A parasitophorous duct in Plasmodium-infected red blood cells.

PMID- 15463517
TI  - Caenorhabditis elegans as a model for parasitic nematodes: a focus on the
      cuticle.
AB  - The phylum Nematoda consists of over half a million species of worms that inhabit
      astoundingly diverse environments. Nematodes can live as obligatory parasites of
      plants and animals, or alternate a parasitic with a free-living life style. The
      fact that the vast majority of species are strictly free living often surprises
      parasitology students, for obviously the highest research priorities in this
      field have involved parasites of medical, veterinary and agricultural importance.
      Here Samuel Politz and Mario Philipp contend that some basic questions concerning
      the biology of the parasite cuticle can be investigated more easily and in
      greater depth in the free-living nematode Caenorhabditis elegans than in the
      parasites themselves.

PMID- 15463518
TI  - Reinfection, exposure and immunity in human schistosomiasis.
AB  - In this review Paul Hagan will focus on the results of the reinfection studies
      that have been completed on Schistosoma mansoni in Kenya and Brazil and on S.
      haematobium in The Gambia. The review will also draw on the data from other
      immunological, molecular and epidemiological studies that have provided
      information that may be relevant to an understanding of immunity in human
      schistosomiasis. No attempt will be made to describe the latest advances that
      have been reported from studies of the animal models of schistosomiasis; these
      are adequately dealt with elsewhere.

PMID- 15463519
TI  - A parasitophorous duct in Plasmodium-infected red blood cells - reply.

PMID- 15463520
TI  - Lipid compartmentalization in erythrocytes parasitized by Plasmodium spp.
AB  - Although reasonably well protected from the host immune system by the erythrocyte
      membrane, the intraerythrocytic malaria parasite has to make that membrane
      compatible with its own requirements for development and multiplication. The
      development of Plasmodium spp brings about major changes in the lipid composition
      of the host cell membrane, as well as in its physical properties. The parasite
      itself has a lipid composition that differs from that of the host cell and an
      intense lipid trafficking seems to occur between intracellular parasite and host
      cell membrane. Here, Ana Paula Simoes, Ben Roelofsen and Jos Op den Kamp discuss
      how, despite serious methodological limitations and the existence of some
      conflicting results, an overall picture of lipid compartmentalization within the
      parasitized erythrocyte is perceived.

PMID- 15463521
TI  - Diversity and selection in Babesia bovis and their impact on vaccine use.
AB  - In the past few years the prospect of a recombinant vaccine effective against the
      cattle hoemoparosite Babesia bovis has almost become a reality. However, in
      Australia, vaccination with live parasites has been practised since before the
      turn of the century and it has recently been proposed that selection of parasites
      resistant to immunity induced by the B. bovis line Ka (since 1979 the only
      component of the live attenuated vaccine) may have occurred. Brian Dalrymple
      examines the evidence for and against this proposal and discusses examples of
      strain diversity and variation and their effect on the long-term viability of
      defined attenuated and recombinant vaccines.

PMID- 15463522
TI  - Cryptosporidiosis: Pathogenesis and immunology.
AB  - Cryptosporidium parvum is an increasingly recognized agent of intestinal
      infection in normal and immunocompromised humans, and in many other animals. The
      intraepithelial cell infection results in villous atrophy, mild submucosal
      inflammation, reduction of brush-border enzymes and a characteristic persistent
      watery diarrhea. The infection is self-limiting in immunocompetent hosts,
      probably because of specific acquired immunity; specific serum and secretory
      antibody responses develop that may be required for clearance and protection
      against reinfection. Passive milk antibody, especially i f in high titers, may be
      partially protective but severe, persistent infection in athymic rodents and
      humans with AIDS demonstrate that T cells are essential for controlling the
      infection. Specific anti-bodies and lymphocyte extracts have been tested in cases
      of cryptosporidiosis but the interpretation of the results remains controversial.
      Here, Shu-Xian Zu, Guo-Dong Fang, Ronald Foyer and Richard Guerrant emphasize
      that effective treatment and prevention remain dependent on advances in our
      understanding of the host cell-parasite relationship.

PMID- 15463523
TI  - Rhoptry organelles of apicomplexan parasites.
AB  - Rhoptries are the unifying structural feature of the intracellular, opicomplexon
      parasites and are implicated in having a central role in host cell invasion.
      Ultrastructural studies of zoites of different genera suggest that the
      participation of rhoptries in the invasion of the respective host cells is
      morphologically similar. However, biochemical analysis of their protein
      constituents reveals a considerable degree of diversity between different
      coccidion parasites. In this article Margaret Perkins asks whether there are
      common structural determinants of the rhoptry components of different genera and
      if the underlying mechanism of rhoptry function is similar in all opicomplexon
      parasites.

PMID- 15463524
TI  - Wastewater reuse in agriculture and the risk of intestinal nematode infection.
AB  - The increasing use of wastewater for crop irrigation in arid and semi-arid zones
      means that wastewater parasitology is becoming on important research area. The
      World Health Organization's (WHO) current guideline states that only treated
      wastewater containing no more than one human intestinal nematode egg per litre
      should be used for irrigation. This guideline was based on very limited
      epidemiological evidence. In this article Rachel Ayres, Rebecca Stott, Duncan
      Mara and Donald Lee describe their recent work in Yorkshire and northeast Brazil
      and suggest that their results may be the first evidence for relaxing the WHO
      guideline for restricted irrigation to no more than ten intestinal nematode eggs
      per litre.

PMID- 15463525
TI  - Which comes first in host-parasite systems: density dependence or parasite
      distribution?

PMID- 15463526
TI  - Is TNF beneficial or deleterious in toxoplasmic encephalitis?

PMID- 15463527
TI  - Can transposable elements be used to drive disease refractoriness genes into
      vector populations?
AB  - A number of biological procedures are currently being considered as alternatives
      to insecticide-based methods for the control of insect vectors of disease. Among
      these are the adaptation of various genetic mechanisms to drive genes of
      interest, such as refractoriness to malaria in mosquitoes, into natural
      populations, for vector control purposes. Here, Margaret Kidwell and Jose Ribeiro
      develop a rationale for the possible use of transposable genetic elements, one of
      these potential drive mechanisms, and some of the problems being faced in seeking
      to determine the feasibility of such a strategy are described.

PMID- 15463528
TI  - Breeding cattle and sheep for resistance to gastrointestinal nematodes.
AB  - Gastrointestinal nematodes are an important cause of reduced production of meat,
      milk and wool in domestic livestock. It is generally believed that problems
      caused by these parasites have increased owing to the intensification of animal
      husbandry(1-3) of resistance to anthelmintics, current research is focussed on
      alternative control strategies that do not rely on anthelmintics. Here, Bram
      Kloosterman, Henk Parmentier and Harm Ploeger review work on the genetic
      resistance of domestic ruminants to these nematodes and discuss the practicality
      of breeding programmes.

PMID- 15463530
TI  - Onchocerca ochengi: Mimic, model or modulator of O. volvulus?
AB  - The cattle parasite, Onchocerca ochengi, is widely distributed in West Africa.
      Significantly, Simulium darnnosum, the vector o f the important human parasite,
      O. volvulus, the cause o f river blindness, also appears to be the vector of O.
      ochengi. For epidemiological reasons it is therefore vital to be able to
      distinguish the infective larvae o f these filoriae. Here, Sandy Trees also
      describes other features of the cattle parasite that make it of significance to
      investigations of human filariases.

PMID- 15463531
TI  - Environmental factors affecting monogeneans parasitic on freshwater fishes.
AB  - The environmental factors that act on fish parasites have received increasing
      attention in recent years. The effects of changing environmental conditions on
      parasite communities can provide valuable information on the effects of pollution
      on the ecosystem as a whole. This, of course, demands that we have a detailed
      knowledge o f parasite communities and the mechanisms acting upon them in a
      variety of natural conditions. Here, Mari Koskivaaro looks at those environmental
      factors that affect monogeneans parasitic on freshwater fishes.

PMID- 15463532
TI  - Praziquantel: The enigmatic antiparasitic.
AB  - Praziquantel (PZQ), a pyrazinoisoquinoline, was introduced as a novel
      anthelmintic in 1975. PZQ is currently the drug of choice for the treatment of a
      wide range of both veterinary and human trematode and cestode infections,
      including human schistosomiasis. Current estimates suggest that 150 million
      humans are infected with schistosomes, and it is expected that PZQ will play the
      lead role in chemotherapeutic control of those infections. Despite the time that
      has passed since its introduction and its obvious importance in global health
      care, it is not yet understood why PZQ is so selective and effective. The target
      molecules for PZQ have not been defined, nor are the sites of its effects within
      the parasites known. Here, Tim Day, James Bennett and Ralph Pax summarize some of
      the progress that has been made toward reaching these objectives in recent years.

PMID- 15463533
TI  - Transformation of Caenorhabditis elegans with genes from parasitic nematodes.
AB  - Our knowledge of many aspects of the molecular biology of animal parasitic
      nematodes has rapidly expanded in recent years but the classical genetic analysis
      of this group of organisms has yet to emerge as a viable discipline. For example,
      it is not possible to routinely perform crosses between single males and females
      to examine the genetic basis of even simple phenotypes such as anthelmintic
      resistance. This has meant that the function of many cloned parasite genes can
      only be inferred from sequence comparison with genes from other organisms where
      the function is known, or by correlation of DNA polymorphisms linked to the gene
      with phenotypic differences between strains or individuals. In the absence of
      classical genetic techniques, a molecular solution is to transform a suitable
      host with the gene of interest, but what defines a suitable host? Here, Warwick
      Grant describes recent work that aims to provide such a host.

PMID- 15463534
TI  - The use of PCR to help quantify the protection provided by impregnated bednets.
AB  - Bednets impregnated with a pyrethroid insecticide are an important recent advance
      in malaria vector control. Here, Suzanne Gokool, Deborah Smith and Chris Curtis
      describe how a combination of field work with specially designed huts and DNA
      fingerprinting of mosquito bloodmeals can be used to help assess whether
      impregnated bednets would give sufficient protection to prevent infection in
      areas of intense malaria transmission.

PMID- 15463536
TI  - SPf66, a candidate synthetic malaria vaccine: Immunogenicity versus protection.

PMID- 15463535
TI  - Production of immunomodulatory neuropeptides by Schistosoma mansoni.

PMID- 15463537
TI  - Do schistosomes exploit the host pro-inflammatory cytokine TNF-alpha for their
      own survival?

PMID- 15463538
TI  - Biochemistry of irradiated parasite vaccines: suggested models for their mode of
      action.
AB  - Irradiated larvae of a remarkably wide range of parasite species induce potent
      protective immunity against subsequent challenge of experimental hosts. Ann Wales
      and John Kusel have studied the irradiated cercariae of Schistosoma mansoni and
      suggest here that the effects of irradiation on conformation and presentation of
      parasite antigens may be crucial in enhancing parasite immunogenicity so
      effectively.

PMID- 15463539
TI  - Perspectives on the bacterial control of vectors in the tropics.
AB  - Biological agents have not found wide application in the control of insects that
      transmit agents of human disease. Fungal pathogens may have a potential for field
      use, but environmental constraints, lack of knowledge of their life cycle, or
      dependence on production in vivo, have prevented their widespread use. In fact,
      sporogenous bacteria are the only biological agents used on a large scale for the
      control of mosquitoes and blackflies that transmit diseases in the tropics. Two
      bacteria, Bacillus thuringiensis sp. israelensis and B. sphaericus are very
      effective for the control of these vectors. In this article, Jean Marc Hougard
      and Christian Back discuss various factors associated with the use of bacteria
      for vector control, and the prospects for further developments.

PMID- 15463540
TI  - Drugs for parasitic diseases.

PMID- 15463541
TI  - Toxoplasmic encephalitis.

PMID- 15463542
TI  - Chitinases in trypanosomatidae and in Trypanosoma brucei brucei: Reply.

PMID- 15463543
TI  - Are antibodies important in mice infected with Plasmodium yoelii?
AB  - It is unwise to extrapolate results, even from one mouse strain to another, when
      attempting to define the mechanisms that control and effect anti-malaria
      immunity. It is important to better characterize the broad range o f possible
      responses that are likely to occur when individuals in an outbred population are
      infected. Here, Peter Sayles and Donald Wossom discuss briefly their views on the
      role of antibody in murine and human malaria infections, based on their work on
      mice infected with Plasmodium yoelii.

PMID- 15463544
TI  - Centrefold: T-cell subsets and cytokines in parasitic infections.

PMID- 15463545
TI  - Is immunity to malaria really short-lived?
AB  - Protection against Plasmodium falciparum malaria is usually considered to be the
      cumulative product of repeated exposure to parasites, and thus a function of age,
      in endemic areas. The recent outbreak of malaria in the central highlands of
      Madagascar gave Philippe Deloron and Claire Chougnet the opportunity to compare
      the incidence of malaria in children and young adults exposed to malaria for the
      first time, with that in older adults who spent their childhood in the study area
      before malaria control was introduced. Protection, as well as immune responses to
      two major P. falciparum antigens, was not related to age. Individuals older than
      40 years were more protected than were younger adults. This increased protection
      was probably due to immunological memory.

PMID- 15463547
TI  - For a few parasites more: Inoculum size, vector control and strain-specific
      immunity to malaria.
AB  - What precipitates malaria illness in an area of intense transmission? Greenwood,
      Marsh and Snow(1) and Marsh(2) have discussed the hypothesis that the severity of
      malaria depends on the size of the inoculum, that is, on the number of
      sporozoites inoculated at one time(3). According to these authors, this is
      suggested by the results of vector control trials in which parasite prevalence
      remained the same but episodes of disease were reduced. This is clearly an
      important observation, but Jo Lines and Jo Armstrong interpret it differently.
      They see the primary implication of these results as being that natural immunity
      to malaria must be largely strain specific, and only if there is strain
      specificity can inoculum size be important. Here they present arguments to
      support this view,and point out that, if there is strain specific immunity, then
      short-term evaluation o f vector control is likely to overestimate its long-term
      benefit.

PMID- 15463546
TI  - A superfamily of Trypanosoma cruzi surface antigens.
AB  - Several genes o f Trypanosoma cruzi encode surface antigens that include an amino
      acid motif that is conserved among bacterial neurominidases. Oscar Campetella,
      Daniel Sdnchez, Juan Jose Cazzulo and Alberto Carlos Frasch here suggest grouping
      these gene families in a superfamily.

PMID- 15463548
TI  - Extracellular development, in vitro, of the erythrocytic cycle of Plasmodium
      falciparum.
AB  - One way to explore the nature of the dependence o f intracellular parasites on
      their host cell is to replace the living host cell with a non-living environment
      that supports development o f the parasite. Bill Trager, Jonathan Williams and
      Gokal Gill describe their methods for obtaining extracellulor development of
      erythrocytic stages of Plasmodium falciparum.

PMID- 15463549
TI  - Guinea worm eradication: four more years to go.
AB  - In 1990, Hopkins and Ruiz-Riben stated that the target date o f the end o f 1995
      for the eradication of dracunculiasis is unrealistic only if it is judged to be
      unimportant. Here, Ralph Muller reviews the situation in each endemic country,
      and looks at possible intervention strategies.

PMID- 15463550
TI  - Malaria--revealing the ties that bind.

PMID- 15463551
TI  - Cognitive function and whipworm infection.

PMID- 15463552
TI  - Economic considerations for helminth control.
AB  - The economic literature related to the control of helminths has grappled with
      three inter-related questions: is the control of helminths a priority health
      issue at a time of increasing resource scarcity, are any of the available options
      affordable and what is the most cost-effective control strategy? In this review
      of the recent literature, Helen Guyatt and David Evans reveal that the attempts
      to answer these questions have not been entirely successful, partly because they
      have sometimes focused on inappropriate issues and partly because some of the
      potentially valuable economic techniques are still being developed. However, the
      major current impediment to the provision of satisfactory answers is the lack of
      precise detail about the nature of the morbidity associated with helminth
      infections.

PMID- 15463553
TI  - The amoeba enigma.
AB  - After more than 70 years of intermittent debate over the true relationship
      between the 'pathogenic' and 'non-pathogenic' forms of Entamoeba histolytica, the
      application of molecular biology has finally yielded an unambiguous answer: these
      are not interconvertible phenotypes of the same parasite, a kind of unicellular
      Jekyll and Hyde, but two quite distinct genetic entities that just happen to look
      the same. But given the overwhelming evidence now available from gene sequences,
      pointing to an evolutionary divergence some tens of millions of years ago, why is
      it that certain eminent workers in the field are still claiming that, at least in
      vitro, conversion between the two phenotypes can take place? In this article Bill
      Spice and John Ackers review recent developments in the molecular biology of E.
      histolytica and assess the continuing controversy over the status of this
      enigmatic parasite.

PMID- 15463554
TI  - Nematode acetylcholinesterases: molecular forms and their potential role in
      nematode behavior.
AB  - Nematode movement is reliant upon the somatic musculature that runs
      longitudinally along the body wall. Neuromuscular synapses occur in the ventral
      and dorsal cords and employ the excitatory neurotransmitter, acetylcholine (ACh),
      for modulation of muscle activity. Acetylcholine activity is terminated by
      hydrolysis by acetylcholinesterase (AChE). Here, Charles Opperman and Stella
      Chang discuss the molecular forms and potential role of this enzyme.

PMID- 15463555
TI  - Schistosomes and host TNF.

PMID- 15463558
TI  - Albendazole as a future antigiardial agent.
AB  - Albendazole, one of the more recently developed of the benzimidazole carbamate
      anthelmintics, has the broadest spectrum of activity of the benzimidazoles
      released to date. In this article, Jim Reynoldson, Andrew Thompson and John
      Horton discuss the role of this drug in the fight against giardiasis.

PMID- 15463559
TI  - RNA polymerase I-mediated protein-coding gene expression in Trypanosoma brucei.
AB  - Protein-coding genes are transcribed by RNA polymerise (pol) II in all eukaryotes
      analyzed to date, with the exception of the protozoan Trypanosoma brucei, where
      pol I can mediate expression of chloramphenicol acetyl transferase (CAT) and
      neomycin phosphotransferase (neo) reporter genes. The addition of the capped 39
      nucleotide (nt) mini-exon to the pre-messenger RNA (mRNA) by trans-splicing in T.
      brucei has presumably led to the uncoupling of the requirement for production of
      mRNA by pol II. Here Hui-min Chung, Mary G-S. Lee and Lex Van der Ploeg review
      the evidence that supports the notion that pol I also transcribes a subset of
      naturally occurring protein-coding genes in T. brucei.

PMID- 15463560
TI  - Immunity to helminths: Ready to tip the biochemical balance?
AB  - Using data from recent laboratory and field studies, Peter Brophy and David
      Pritchard here summarize our current understanding of the approximate sequence of
      events leading to protective immune responses against some chronic parasitic
      helminth infections.

PMID- 15463561
TI  - Cytokines, free radicals and resistance to Eimeria.
AB  - The cytokine, gamma-interferon (IFN-gamma), which is produced by CD4(+) T cells,
      plays a crucial role in host resistance to Eimeria infections. Karen Ovington and
      Nick Smith propose that free oxygen radical generation by leukocytes in response
      to infection with Eimeria is the result of activation by IFN-gamma. The
      functional role of free oxygen radicals is unclear but these highly reactive
      radicals are produced by the leukocytes that infiltrate the intestine in large
      numbers during infection, and the parasites,enterocytes and cells of the immune
      system may all be vulnerable to oxidative damage. Gamma-interferon also appears
      to induce the enterocytes inhabited by Eimeria to turn against the parasite. The
      authors draw from literature documenting similar effects on other protozoa,
      especially Leishmania and Plasmodium, and speculate that reactive nitrogen
      intermediates produced by enterocytes have a functional role in resistance to
      Eimeria.

PMID- 15463562
TI  - Pfl I-I and Pf332: two giant proteins synthesized in erythrocytes infected with
      Plasmodium falciparum.
AB  - Although the malaria parasite develops within erythrocytes, it has to modify the
      surrounding red blood cell membrane for its intracellular survival and
      maturation. These changes include the translocation of proteins across the
      parasite and the parasitophorous vacuole membranes to the host membrane. In this
      review, Denise Mattei, Katherine Hinterberg and Artur Scherf focus on two
      distinct giant parasite molecules of unprecedented size (approximately one MDa),
      called Pf332 and PflI-I, that are synthesized and exported into the cytoplasm of
      the host cell in the asexual and sexual blood stages of Plasmodium falciparum,
      respectively. The corresponding genes are located in genetically unstable
      subtelomeric chromosome regions.

PMID- 15463563
TI  - Health or wealth?

PMID- 15463564
TI  - HLA effects in malaria: increased parasite-killing immunity or reduced
      immunopathology?

PMID- 15463565
TI  - Effects of ultraviolet B irradiation on cutaneous leishmaniasis.
AB  - Protection against many infectious diseases is mediated by cellular immunity in
      the competent host. Ultraviolet (UV) radiation, a component of sunlight, is a
      potent suppressor of cell-mediated immune responses. Suzanne Holmes Giannini
      discusses the possible relevance of ambient levels of UVB to pathogenesis and
      immunity in infectious diseases, with special reference to cutaneous
      leishmaniasis.

PMID- 15463566
TI  - Heligmosomoides polygyrus: a model for chronic gastrointestinal helminthiasis.
AB  - Establishment of chronic infections and strain-dependent variation in resistance
      to challenge infections are well-known features of the relationship between mice
      and the intestinal nematode parasite Heligmosomoides polygyrus. Here, Fernando
      Monroy and Javier Enriquez examine host responses, immunogenic and nonimmunogenic
      antigens of the parasite, and parasite immune evasion strategies in this useful
      laboratory mouse model of nematode parasitism of mammals.

PMID- 15463570
TI  - Morbidity in schistosomiasis mansoni II.

PMID- 15463568
TI  - Morbidity in schistos mansoni I.

PMID- 15463571
TI  - HLA, malaria and dominant protective associations.

PMID- 15463572
TI  - Toxic pollution and parasitism in freshwater fish.
AB  - As aquatic habitats throughout the world are increasingly contaminated with toxic
      chemicals, toxicologist strive to determine what impact these substances will
      have an biological systems. So far, the effects of this type of pollution on fish
      parasites has received little attention, despite their important status as
      determinants of fish health. Robert Poulin discusses the many ways in which toxic
      pollution may affect infections of metazoan parasites in freshwater fish. Effects
      on fish immunity, parasites survival and intermediate host populations are not
      independent, and currently the outcome of toxic pollution and parasitism in fish
      is impossible to predict. Future research will have to answer several questions
      if we are to understand and forecast pollution-mediated changes in parasitism, an
      urgent challenge for ecotoxicologists and fish parasitologists alike.

PMID- 15463573
TI  - Travellers' malaria.
AB  - The risk of malaria poses travellers and their advisers with difficult problems
      as drug resistance spreads worldwide. Protection against infection rests on
      travellers' knowledge of the risk of malaria, on their avoidance of malaria
      vectors and on their compliant use of chemoprophylaxis. In this article, Robert
      Ste f fen and Ronald Behrens explain that one of the priorities for reducing
      malaria morbidity is to improve travellers' use of personal protection against
      mosquito bites. They show that none of the drugs, or combinations thereof,
      provide a 100% efficacy, owing to increasing drug resistance, mainly of
      Plasmodium falciparum. The commonly used drugs for malaria prophylaxis
      (mefloquine, doxycycline, chloroquine and proguanil) often cause minor side
      effects. All, except proguanil, have also been occasionally associated with
      severe adverse effects. Other drugs (pyrimethaminelsul fadoxine, amodioquine) are
      not suitable for chemoprophylaxis because of unacceptable adverse reactions. The
      use of drugs for self therapy is constrained by limitations of toxicity and
      efficacy, and the added difficulties of defining indications for safe and
      appropriate use.

PMID- 15463574
TI  - Identification of filarial larvae in vectors by DNA hybridization.
AB  - Infectivity rates of insect vectors are the best criteria by which to assess the
      transmission of filarial parasites and the efficacy of filariasis control
      programs. Currently available DNA probes can be used to estimate the proportion
      of vectors containing larvae of a given filarial species but provide no
      information on three other important variables in the transmission dynamics of
      filarial nematodes: the developmental stage, the location and the actual number
      of larvae that are present in the vector, all of which can be reliably determined
      by microscopy. However, species identification is often difficult and sometimes
      impossible by conventional microscopy, which requires morphologically intact
      specimens. DNA is tough and DNA probing can identify worms that are dead and that
      have lost morphologic integrity; it also permits multiple analyses of the same
      specimen with different probes and has the potential for simultaneous processing
      of very large numbers of samples. Here, Senaroth Dissonoyake and Willy Piessens
      outline the route to the development of species- and life cycle stage-specific
      DNA/RNA probing reagents, and simple, reliable and quantitative technologies that
      can supplement and ultimately replace microscopic dissection.

PMID- 15463575
TI  - Rapid diagnosis of malaria by fluorescence microscopy.
AB  - The routine procedure for detection of blood stages of Plasmodium spp involves
      Giemsa staining of thin and thick blood smears. This procedure, although simple,
      is time consuming, and its interpretation is dependent upon the training and
      experience of the observer. New methods for malaria diagnosis still require
      considerable financial outlay for specialist equipment and re-training of staff
      In this article, Hiko Kawamoto and Peter Billingsley discuss an efficient method
      for the detection of malaria parasites using low-cost, paired filters adapted for
      standard light microscopes and acridine orange staining.

PMID- 15463576
TI  - Phylogeny of plasmodium falciparum.

PMID- 15463577
TI  - Modeling transmission dynamics of stage-specific malaria vaccines.
AB  - Population effects of malaria vaccination programs will depend on a complex
      interaction of the stage specificity of the vaccine, its duration of
      effectiveness, whether it is responsive to natural boosting, the strategy
      implemented, the proportion vaccinated and the pre-existing endemic conditions.
      In this article, Elizabeth Halloran and Claudio Struchiner review models of
      malaria transmission that incorporate aspects of immunity relevant to studying
      the effects of stage-specific malaria vaccination programs. They discuss the
      difference in the assumptions and applicability of the models and compare their
      predictions. Experience with malaria has demonstrated the difficulty in
      eliminating transmission, so emphasis needs to be on the new host-parasite
      balance that will be induced by the vaccination program. Although Halloran and
      Struchiner advise caution in interpreting the results of such models, they
      conclude that quantitative and theoretical analysis will be important in planning
      and evaluating interventions with malaria vaccines.

PMID- 15463578
TI  - Opisthorchis viverrini and cholangiocarcinoma in Northeast Thailand.
AB  - Population-based research is beginning to show clearly the devastating impact
      that Opisthorchis viverrini infection has on the Laos-descendent population of
      Northeast Thailand who love to eat uncooked meat and fish, one of which being the
      parasite's intermediate host: cyprinoid fish. Here, Melissa Haswell-Elkins,
      Paiboon Sithithaworn and David Elkins discuss the parasite's life cycle and
      epidemiology, highlighting the close relationship between this infection and bile
      duct carcinoma, which is a major cause of death among adults in rural Northeast
      Thailand.

PMID- 15463579
TI  - Hohlzylinders.

PMID- 15463580
TI  - Heterogeneity of host-related DNA sequences in schistosomes.

PMID- 15463581
TI  - Plasmodium falciparum: birds to humans.

PMID- 15463582
TI  - Genetic variation in tsetse flies and implications for trypanosomiasis.
AB  - The role of tsetse flies in the transmission of trypanosomes has been known for
      nearly 100 years, their economic and public health impact justifying much of the
      research. About 20 years ago, no genetic variants of tsetses were known but the
      discovery of six visible mutants and the application o f protein electrophoretic
      techniques have changed the situation. During the intervening years many
      techniques have been developed to study the biology of the approximately 30 known
      species and subspecies of Glossina. Here, Ron Gooding summarizes recent
      developments in the estimation o f genetic variation in tsetse populations and
      speculates on the implications of this variation to population structure,
      vectorial capacity and disease control strategies.

PMID- 15463583
TI  - High-density lipoprotein-mediated lysis of trypanosomes.
AB  - Nearly 90 years after the discovery that certain African trypanosornes were
      killed by normal human serum, we still do not understand how this innate
      trypanocidal factor works. Biochemical studies have provided us with an unlikely
      candidate: human high-density lipoprotein (HDL). This trypanosome lytic factor
      (TLF) from human serum is important since its activity restricts the host range
      of Trypanosoma brucei brucei, and the expression of this natural killing factor
      in cattle would represent a novel approach to the control of bovine
      tryponosomiasis. Here, Steve Hajduk, Kristin Hager and Jeffrey Esko discuss
      evidence for the TLF being a minor subclass of serum HDL and propose a mechanism
      for lysis based on the binding, endocytosis and lysosomal targeting of TLF.

PMID- 15463584
TI  - Epidemiological modelling for onchocerciasis control.
AB  - Planning and evaluation of parasitic disease control is complicated by the many
      interacting factors that jointly determine the epidemiological trends under
      different control strategies. The Onchocerciasis Control Programme (OCP) of the
      World Health Organization in West Africa has recognized this problem and uses
      epidemiological modelling as on aid to addressing control questions. Dik Habbema,
      Edoh Soumbey Alley, Anton Plaisier, Gerrit van Oortmorssen and Hans Remme
      describe the organization of modelling in the OCP and summarize the most
      important achievements thus far. The experience with applied modelling in OCP is
      of considerable interest for other disease control programmes.

PMID- 15463585
TI  - Estimation of population at risk of infection and number of cases of
      Leishmaniasis.
AB  - In this paper, Dick Ashford, Philippe Desjeux and Peter deRaadt attempt to
      estimate the total number of people at risk of acquiring disease caused by
      infection with Leishmania spp. In many areas a very small risk is distributed
      among large numbers of people so, although the number of people at risk may be
      large, the number of infections may be very small. An estimate of the global
      annual incidence of new cases has also been made. This refers to reported
      clinical disease and probably grossly underestimates the number of infections.
      The methods by which the estimates have been made are specified so that they, as
      well as the estimates themselves, may be criticized and modified with some degree
      of objectivity.

PMID- 15463586
TI  - Does facilitation imply a threshold for the eradication of lymphatic filariasis?

PMID- 15463588
TI  - Immunoepidemiology of intestinal helminths: pattern and process.

PMID- 15463587
TI  - Vector competence.

PMID- 15463589
TI  - Malaria vector analysis and control.
AB  - Antivector measures in malaria control should aim for a cost-effective reduction
      of the transmission potential ideally to below the critical level for sustained
      transmission. The available measures include those that decrease vector
      abundance, vector-human contact and vector survival rate or that increase the
      length of the sporogonic cycle. These have widely different impact on malaria
      transmission, as shown by epidemiological modelling. Direct modification of
      vector receptivity to Plasmodium is also hypothetically attainable by the use of
      transmission-blocking vaccines or by genetic manipulation and replacement of the
      vector population. Vector analysis constitutes the essential prerequisite for
      basic malaria epidemiology as well as for the development, planning and
      evaluation of antivector measures. The rationale, the problems and the
      perspectives of vector analysis are reviewed here by Mario Coluzzi, on the basis
      of his experience with Afrotropical and Mediterranean malaria vectors.

PMID- 15463590
TI  - Crossreactive antigens between life cycle stages of plasmodium falciparum.
AB  - The high mortality and morbidity induced by falciparum malaria has motivated
      research to find an efficient antimalarial vaccine. The parasite has a complex
      life cycle, both in the mosquito and human hosts, and presents a number of
      potential targets for vaccine-induced immune attack. Here, Inge Moelans and John
      Schoenmakers discuss how the search for protective antigens has been complicated
      by the discovery of multiple crossreactivities between different parasite
      proteins.

PMID- 15463591
TI  - Arbovirus-mosquito interactions and vector specificity.
AB  - Mosquito-borne arboviruses cause important and expanding disease problems. In
      this article, Colin Leake reviews the increasing knowledge of the complex
      interaction of arboviruses with their mosquito vectors and mosquito cells, in
      vitro, and considers the factors influencing vector specificity and vector
      competence.

PMID- 15463592
TI  - Mathematical models for African trypanosomiasis.

PMID- 15463594
TI  - The role of pheromones in tick biology.
AB  - Ticks are important vectors of pathogens that cause human and animal disease.
      Pheromones play a role of fundamental importance in intraspecies communication.
      Here, Gordon Hamilton discusses how these chemical messengers play a role in mate
      location, host location, and survival in adverse conditions, and how manipulation
      of this chemical communication system may provide a potential method of tick
      control.

PMID- 15463596
TI  - Does immunosuppression promote drug resistance in malaria?

PMID- 15463597
TI  - Pentastomids and the immune response.
AB  - Pentastomids are a class of crustacean endoparosites that, as adults, parasitize
      the respiratory tract of vertebrates. They have evolved some unique strategies
      for long-term survival in vertebrate lungs which appear to be equally useful in
      thwarting inflammatory responses in the tissues of intermediate hosts. In this
      article, John Riley outlines the possible biological roles and immunological
      relevance of pentastomid excretory/secretory (E/S) products that may be important
      to parasite survival.

PMID- 15463598
TI  - Treatment of onchocerciasis with ivermectin in Sierra Leone.
AB  - Ivermectin chemotherapy is proving to be a major advance in the management of
      onchocerciasis. In this article, James Whitworth reviews the work done on
      onchocerciasis and ivermectin in Sierra Leone and examines the evidence that mass
      treatment might control the clinical features of the disease and its transmission
      in West Africa. Ivermectin is safe and effectively reduces microfilarial (mf)
      loads, with major improvement in some ocular manifestations o f disease. This
      alone makes mass distribution to communities at risk of blindness worthwhile,
      even though the impact on other clinical features is less clear cut. Repeated
      doses have a cumulative effect on adult worms, which may cause more reduction in
      transmission than hitherto thought likely.

PMID- 15463599
TI  - Strategies for malaria control in Colombia.
AB  - Attempts at malaria eradication this century have been highly effective but early
      successes have not been sustained. This has been ascribed to the lack of
      community involvement in these campaigns. Colombia has put huge effort into
      malaria control on a number of fronts, from vaccine development to the evaluation
      of the integrated use of more traditional methods. William Rojas, Fernando
      Penaranda and Mouricio Echavarria describe a pilot programme for integrated
      malaria control in Colombia whose success they attribute to committed community
      participation.

PMID- 15463600
TI  - Romancing the genome.

PMID- 15463601
TI  - Ivermectin-facilitated immunity.

PMID- 15463602
TI  - Electron-transfer complexes of mitochondria in Ascaris suum.
AB  - During the past ten years, studies on the respiratory chain of mitochondria in
      parasites have progressed to provide new insight into the structural organization
      and physiological significance of the mitochondrial respiratory chain. In this
      review, Kiyoshi Kita focuses on studies on the respiratory chain of Ascaris
      mitochondria in which major advances have recently been made. These include the
      identification of the unique features of anaerobic respiration, the elucidation
      of the molecular structures of the components involved and an understanding of
      the evolution of the energy transducing system and of the developmental changes
      that occur during the life cycle of this nematode.

PMID- 15463603
TI  - Sexually transmitted diseases in animals.
AB  - The sexual transmission of infectious agents is one of a suite of characteristics
      that enhance the ability of an infection to persist in low-density populations.
      Gary Smith and Andrew Dobson review the characteristics and control of sexually
      transmitted diseases in domestic animals and wildlife species.

PMID- 15463604
TI  - Serum IgE levels, helminth infection and socioeconomic change.

PMID- 15463606
TI  - Chronotherapy of malaria.

PMID- 15463607
TI  - Animal models for the study of immunity in human filariasis.
AB  - A major challenge to the development of vaccines against human lymphatic
      filariasis and onchocerciasis is to direct the immune response toward elimination
      of the early, prepathogenic larval stages and away from responses that mediate
      pathology. In this review, James Lok and David Abraham discuss the various animal
      models that have been used to investigate the pathways leading to immunity,
      immunological tolerance and chronic pathology in these diseases. Owing to the
      strict host specificities of the human-dwelling filariae, no single model serves
      to duplicate exactly all these aspects. Nevertheless, it has been possible to
      demonstrate a protective immune response invoked by and directed against incoming
      third-stage larvae of both lymphatic and skin-dwelling filariae. The fact that
      subsets of the sequelae of human filarial infection can be duplicated in animal
      systems should also aid in unravelling the mechanisms determining the course of
      infection and in ensuring that vaccine candidates do not produce an inappropriate
      immunopathological response. A proposed scheme for using animal models in
      screening candidates for a vaccine against Onchocerca volvulus is presented.

PMID- 15463608
TI  - Genetics of Biomphalaria glabrata and its effect on the outcome of Schistosoma
      mansoni infection.
AB  - The genetics of the snail Biomphalaria glabrata is better characterized than that
      of any other intermediate host of schistosomes of humans. Using techniques of
      selective breeding, several snail stocks have been developed that consistently
      display resistant or susceptible phenotypes. Investigators using these stocks
      have learned that several snail and parasite genes influence the course of
      parasite development. Here, Charles Richards, Matty Knight and Fred Lewis discuss
      the importance of the snail's genetics in categorizing resistance in this complex
      invertebrate, some recent molecular evidence that may help us understand several
      of the problems that still remain, and some challenges lying ahead for
      investigators in this field.

PMID- 15463609
TI  - Leishmania: sex, lies and karyotype.
AB  - The exploration of the genome of the tryponosomotid protozoan Leishmania has been
      difficult until recently owing to a number of obstacles, not least our ignorance
      of the ploidy and of the number of chromosomes (as in many other protozoa, the
      latter do not condense during mitosis), the uncertainty of the species concept in
      these allegedly asexual protozoa and the absence of classical genetic studies.
      Here, Patrick Bastien, Christine Bloineou and Michel Pages discuss the advances
      in this field brought about by the advent of molecular biology and its
      techniques, with on emphasis on ploidy and genetic exchange. In particular, they
      discuss the data from pulsed field gel electrophoresis (PFGE). When coupled with
      DNA restriction analysis, PFGE constitutes a powerful tool for the direct
      examination o f chromosomes of protozoa.

PMID- 15463610
TI  - Molecular diagnostics for plant nematodes.
AB  - Plant parasitic nematodes are a source of considerable economic loss to arable
      farmers. However, the cost of nematode control is also escalating, both in
      financial and environmental terms. Nevertheless, there are alternative methods of
      control in current use. As Tom Powers emphasizes in this article, to be
      effective, crop rotation and the use of resistant strains of host plant need to
      be accompanied by sensitive methods for parasite strain identification.
      Morphologically, there is little by which to separate nematode pothotypes and
      consequently technologies are being introduced to tackle these problems at the
      level of their genes.

PMID- 15463611
TI  - The clinical significance of ubiquity.

PMID- 15463612
TI  - Cysticercosis in Asian-Pacific regions.

PMID- 15463613
TI  - The specificity of chloroquine.

PMID- 15463614
TI  - The mosquito genome: organization, evolution and manipulation.
AB  - Apart from the genetic flexibility of the vectors, impediments to the control of
      vector-borne diseases include the rapid spread of drug resistance throughout
      parasite populations, the increasing movement of people to and from disease
      endemic regions and the limited funds and public health infrastructures of most
      developing countries. The widely used residual insecticides and antiparasitic
      drugs have been inadequate solutions to the problem of vector-borne disease
      control. New approaches are needed. The enormous impact of recent developments in
      molecular genetics on the understanding of basic biology and human disease has
      stimulated a re-examination of the prospects for genetic manipulation of vector
      populations as a means for reducing or eliminating vector-borne diseases,
      especially malarial. Although control scenarios that exploit this technology may
      never be realized, Nora Besansky and Frank Collins emphasize that the increase in
      knowledge of basic mosquito biology on which these ideas depend will inevitably
      stimulate novel approaches to the control of mosquito-borne diseases.

PMID- 15463615
TI  - The chromosomes of Leishmania.
AB  - Chromosome size polymorphisms occur in Leishmania such that each strain of a
      given species has a distinctive molecular karyotype. Despite this variability,
      the chromosomal similarities among closely related strains of Leishmania are
      sufficiently characteristic to permit classification of unidentified clinical
      isolates. Mechanisms generating chromosome size polymorphisms are related to
      chromosomal evolution. In this review, Geoffrey Lighthall and Suzanne Giannini
      explain that the chromosomal profiles of members of different species may be
      diverging from a conserved 'consensus' karyotype at different rates, and present
      a current understanding of the genomic organization of Leishmania with emphasis
      on chromosomal elements.

PMID- 15463616
TI  - The role of T-cell anergy in the immunomodulation of schistosomiasis.
AB  - Schistosomes are capable of causing severe tissue damage, which results from the
      granulomatous inflammation that develops around the parasite eggs. Characteristic
      of this inflammatory process is its gradual, spontaneous down-regulation
      (immunomodulation) as the disease progresses. There has been general agreement
      that the granulomatous inflammation is a consequence of T(H)-cell-mediated
      delayed-type hypersensitivity to egg antigens. However, the basis of
      immunomodulation is less clear and has been attributed to various causes. In this
      review, Miguel Stadecker proposes a novel mechanism of immunomodulation based on
      the observation that accessory cells from schistosome-infected individuals are
      capable of inducing a state of unresponsiveness or energy in a subpopulation of
      antigen-specific CD4(+) T(H)-cell clones identified with delayed-type
      hypersensitivity reactions.

PMID- 15463617
TI  - Invasion and development strategies of Ichthyophthirius multifiliis, a parasitic
      ciliate of fish.
AB  - Like many other parasites, Ichthyophthirius multifliis faces critical changes
      when moving between free-living and parasitic phases. This ciliate alternates
      between feeding in the epithelium of freshwater fishes and swimming and encysting
      in fresh water. Several organelles appear to play key roles in successful
      negotiation o f these changes. Margaret Ewing and Katherine Kocan discuss a
      variety of cellular components important in host invasion and development of the
      parasite, with particular attention given to mucocysts, extrusive organelles
      whose secretions appear to be essential to both life cycle phase changes.

PMID- 15463618
TI  - Interbreeding, monophyly and the genetic yardstick: species concepts in
      parasites.
AB  - The biological species concept defines species on the criterion of interbreeding.
      This may not be applicable to many parasites that are capable of self
      fertilization and asexual reproduction. In this review, Alan Lymbery explores
      alternative concepts that may be applied to recognize species in such groups,
      using the cestode genus Echinococcus as an example. Two conclusions can be drawn.
      First, that the applicability of the biological species concept should not be
      dismissed without some knowledge o f the frequency of interbreeding in natural
      populations. Second, that where interbreeding is absent or rare, species should
      be delimited on the basis o f both monophyletic origin and genetic distinctness.

PMID- 15463620
TI  - Made in the USA.

PMID- 15463619
TI  - Treatment of Onchocerciasis with ivermectin in Central America.
AB  - The success o f ivermectin in controlling transmission of Onchocerca volvulus in
      Guatemala suggests a broader role for this drug than morbidity control alone. In
      this article Ed Cupp reviews recent findings from a three-year pilot study in
      that country which evaluated the effects of recurrent semiannual treatment on
      several important factors associated with the biology o f river blindness. These
      results illustrate the range o f beneficial effects that occur not only for this
      disease but for other parasitisms when this drug is administered at the community
      level.

PMID- 15463621
TI  - Is culture of the entire plasmodium cycle, in vitro, now a reality?

PMID- 15463622
TI  - Towards a high-resolution map of the Plasmodium falciparum genome.
AB  - Until recently very little was known about the genome of Plasmodium falciparum.
      The situation has changed considerably with the advent of pulsed field gradient
      electrophoresis and yeast artificial chromosome technologies. It should now be
      possible to generate a high-resolution map within a few years. Here, Tony
      Triglia, Thomas Wellems and David Kemp review current knowledge.

PMID- 15463623
TI  - Surface antigen variability and variation in Giardia lamblia.
AB  - Recent studies show that Giardia isolates are heterogeneous but fall into at
      least three groups as determined by a number of complementary techniques. Giardia
      undergoes surface antigenic variation, both in vitro, and in humans and other
      animal model infections. Many of the characteristics of antigenic variation and
      the proteins involved, called variant-specific surface proteins (VSPs), are
      unique. The sequences of five VSPs reveal a family of cysteine-rich proteins.
      Here Theodore Nash reviews the relationship between antigenic variation and
      Giardia heterogeneity.

PMID- 15463625
TI  - Random amplified polymorphic DNA.

PMID- 15463627
TI  - Vaccination against warble fly?

PMID- 15463628
TI  - Interactions between Trypanosoma brucei and CD8+ T cells.
AB  - The mechanisms for several important features o f African trypanosomiasis are
      still largely unexplained. These include (1) the occurrence of parasite growth
      promoting molecules provided by the host, (2) polyclonal T- and B-cell activation
      and the development of immunosuppression and (3) neuropsychiatric signs. Here
      Tomas Olsson, Moiz Bakhiet and Krister Kristensson focus on interactive events
      between Trypanosoma brucei and CD8(+) T cells, and the release of a diffusible
      molecule from T. brucei that triggers CD8(+) T cells to produce interferon-gamma
      (IFN-gamma). This cytokine provides a growth stimulus for the parasite and
      modulates events in the host's immune and nervous systems.

PMID- 15463629
TI  - The genetic structure of malaria parasite populations.
AB  - The suggestion that a clonal population structure may typify Plasmodium
      populations has proved highly controversial. For the most part, existing
      population genetic data from wild populations contradict the idea and are
      consistent with randomly interbreeding populations. In this article, Andrew Read
      and Koren Day point out that these data could also be consistent with population
      subdivision and frequent nonrandom mating, which current sampling methods would
      be incapable of detecting.

PMID- 15463631
TI  - Biased males and detecting disease.

PMID- 15463630
TI  - Nematode surface coats: actively evading immunity.
AB  - The classical view of nematode parasites depicts their surface as the epicuticle,
      the outermost layer of a thick extracellular cuticle. However, many stages and
      species of nematode have been found to bear an electron-dense cuter envelope
      distinct from and distal to the epicuticle itself. In this review, Mark Blaxter
      and colleagues summarize some wide-ranging studies in both free-living and
      parasitic nematodes, and suggest that, in many cases, it is the surface coat
      rather than the cuticle that displays dynamic properties thought to be involved
      in immune evasion by parasites.

PMID- 15463632
TI  - The biology of the heat shock response in parasites.
AB  - The heat shock response is a general homeostatic mechanism that protects cells
      and the entire organism from the deleterious effects of environmental stress. It
      has been shown that heat shock proteins play major roles in many cellular
      processes and have a unique role in several areas of cell biology, from chronic
      degenerative diseases to immunology and from cancer research to interactions
      between host and parasite. In this review, Bruno Maresca and Luisella Carratu
      deal with some of the unique characteristics of the heat shock response in
      parasitic organisms.

PMID- 15463633
TI  - Geographic models and control of cattle liver flukes in the Southern USA.
AB  - John Malone and Stanley Zukowski describe climate forecast and soil hydrology
      based geographic information system models of snail habitat extent that provide
      an environmental context for site-specific mathematical models of fascioliasis.
      These have potential for the development of broad-scale control models that
      include a cost-benefit analysis component.

PMID- 15463634
TI  - Acquired immunity in schistosomiasis.

PMID- 15463635
TI  - Malaria diagnosis by fluorescence microscopy.

PMID- 15463637
TI  - Chitinases in trypanosomatidae: a cautionary note.

PMID- 15463638
TI  - Underestimation of Schistosoma mansoni prevalences.
AB  - Field methods used for detecting Schistosoma mansoni infection miss a certain
      proportion of the infections. Prevalences of infection appear to be far under
      estimated by faecal screening, with important consequences for control and
      research. Sake de Vlos and Bruno Gryseels investigate how the number of
      undetected infections can be statistically inferred from population surveys.

PMID- 15463639
TI  - Why does liver fibrosis occur in schistosomiasis?
AB  - Schistosomiasis is one of the most prevalent of several chronic inflammatory
      diseases in which morbidity results primarily from tissue scarring. New concepts
      regarding the molecular pathogenesis of scar formation are being applied in
      research efforts to define the basis of liver fibrosis in schistosomiasis. Such
      investigations have led to the identification of an apparently novel lymphokine,
      fibroblast stimulating factor-I (FsF-I), produced in the egg granulomas. FsF-1
      and other granulomo-derived fibrogenic cytokines may represent the molecular
      links between periovular granulomotous inflammation and hepatic fibrosis. Here,
      David Wyler postulates that the unmodified production of these f brogenic signals
      may be responsible for the development of severe hepatic fibrosis in the
      subpopulotion of infected individuals who develop this complication.

PMID- 15463640
TI  - The pathway of hemoglobin degradation in malaria parasites.
AB  - Hemoglobin degradation in malaria parasites appears to be a vital and massive
      undertaking during intraerythrocytic development. An ordered pathway exists that
      efficiently catabolizes hemoglobin to yield amino acids that the parasite uses as
      a nutrient source, and that co-ordinates the resultant heme into a remarkable
      crystalline structure called hemozoin. Daniel Goldberg and Andrew Slater explain
      that the enzymes involved are specific and present prime targets for
      chemotherapeutic intervention.

PMID- 15463641
TI  - Altered membrane permeability: a new approach to malaria chemotherapy.
AB  - During its development: in the host erythrocyte, the malarial parasite causes
      profound alterations in the permeability of the host cell membrane. Nucleoside
      transport pathways, which are induced by the parasite in the host erythrocyte
      membrane, have properties significantly different from those of the host cell.
      Here, Annette Gero and Joanne Upston review the current knowledge o f the
      parasite-induced transporters and show that they can be used to selectively
      direct cytotoxic compounds into the parasite-infected cell, thereby indicating
      their chemotherapeutic potential.

PMID- 15463642
TI  - Sexing schistosome larvae.
AB  - Biological and immunological factors may influence changes in sex ratios at
      different points of the schistosome life cycle, resulting in the fact that female
      schistosomes are significantly outnumbered by males in chronic infections of
      snails and mammalian hosts. Analysis of this phenomenon has long been hampered by
      shortcomings in the methods used to determine sex ratios. Here, Robin Gasser
      describes recently developed molecular methods for sexing schistosome larvae.
      These have opened the way towards understanding why sex ratios become male biased
      and allow a proper assessment of its consequences in the epidemiology, diagnosis
      and pathology of infection.

PMID- 15463643
TI  - Sex: why bother?

PMID- 15463644
TI  - Genetics of insecticide resistance in mosquito vectors of disease.
AB  - Early studies on the genetics of insecticide resistance showed that single major
      semi-dominant genes were generally involved, and biochemical studies defined a
      limited number of enzymes and structural nerve proteins that were encoded by
      these genes. Recent advances in resistance detection now allow the measurement of
      genotype frequencies for some of these resistance mechanisms. Molecular studies
      are in progress for most of the major resistance genes, and the amplified
      esterase B(1) gene in Culex quinquefasciatus has been cloned. Changes in
      resistance gene expression occur, with increasing age of the adult insect, by way
      of specific mechanisms, and amplified esterase-based resistance genes that are
      not expressed can occur in aphids. Here Janet Hemingway assesses current
      knowledge of the genetics of insecticide resistance in mosquitoes.

PMID- 15463645
TI  - Genes and genomes of parasitic nematodes.
AB  - Our knowledge of gene and genome organization in nematodes is growing rapidly,
      partly as a result of the Caenorhabditis elegans genome project. Here Martin
      Hammond and Ted Bianco review what is known about the organization of genes and
      genomes in parasitic nematode species, using information gained from molecular
      and cytological approaches. They suggest that there are implications not only for
      a wide range of problems in parasitology but also for our understanding of genome
      evolution in eukaryotes.

PMID- 15463646
TI  - Leishmania: sex, karyotypes and population genetics.

PMID- 15463647
TI  - Making mosquitoes harmless.

PMID- 15463649
TI  - HIV and malaria: a lesson in immunology?
AB  - HIV is now common in many areas of Africa that are also highly endemic for
      malaria. In this article, Geoff Butcher summarizes the available data on the
      possible interaction o f HIV and malaria, and shows that the course of falciparum
      malaria is virtually unaffected by the presence of HIV. This raises significant
      questions for our understanding of immunity to the asexual blood stages of human
      malaria and the use of animal models in malaria research.

PMID- 15463650
TI  - Cytokines: making the right choice.
AB  - Fred Finkelmon and Joseph Urban propose that optimal host defense against
      different classes of parasite depends upon induction of different sets of immune
      effector mechanisms, which are, in turn, dependent upon secretion of different
      sets of cytokines. The authors suggest that hosts identify characteristics common
      to parasites of a given type as those triggers that stimulate secretion of the
      proper cytokine set.

PMID- 15463651
TI  - Strongyloides fuelleborni kellyi: infection and disease in Papua New Guinea.
AB  - A series o f unexplained deaths of two-month-old babies at on isolated mission
      station in Papua New Guinea led to the description o f a parasitic disease with
      unique and intriguing features. The parasite was named Strongyloides fuelleborni
      kellyi; S. fuelleborni is normally a parasite of non-human primates in Africa and
      Asia and of humans in Africa. How did the new subspecies reach non-human primate
      free New Guinea? How do infants become infected in the first few days after
      birth? Why is the fatal disease restricted to two small areas while the infection
      itself is widespread? Ten years of study have only begun to indicate answers, as
      discussed here by Dick Ashford, Guy Barnish and Mark Viney.

PMID- 15463652
TI  - Anti-malarial antibodies in twins.

PMID- 15463653
TI  - Taxonomic status of Blastocystis hominis.

PMID- 15463654
TI  - Concomitant immunity in schistosomiasis.

PMID- 15463655
TI  - Ectoparasites: direct impact on host fitness.
AB  - Despite being restricted to the host's first line of defence (the integument,
      away from vital organs), ectoparasite damage has a pronounced impact on host
      fitness. This generalization can be explained by the reduced dependence of most
      ectoparasites on their individual host, which minimizes the fitness loss linked
      to host death. This explanation implies that permanent ectoparasites evolve less
      'aggressively' than do either nest or field ectoparasites. This, and other
      determinants of ectoparasitic virulence are discussed here by Tovi Lehmann.

PMID- 15463657
TI  - Taxonomic status of Blastocystis hominis: reply.

PMID- 15463656
TI  - Host resistance in cattle tick control.
AB  - Cattle ticks are an important constraint on the livestock industry, particularly
      in tropical and subtropical areas, mainly because of the diseases they transmit
      and the costs of control. Conventional control is by means of acaricides;
      although there are still serious drawbacks, these can be minimized by a strategic
      approach. In this review Julio de Castro and Robin Newson look at alternatives.
      One is to make use of the host's innate abilities. In the simplest situation,
      where no control measures are applied, the animals develop their own protective
      immunity against ticks and tick-borne diseases (TBDs). Alternatively, breeds of
      cattle with naturally high resistance to ticks can be used, enhanced by
      selection. Methods of immunizing cattle against ticks are also under development.
      Ideally, ticks should be managed at an economically acceptable level by a
      combination of techniques, supported where necessary by vaccination against TBDs.

PMID- 15463658
TI  - Anti-malarial antibodies in twins: reply.

PMID- 15463659
TI  - Chromosome size polymorphism and DNA rearrangements in plasmodium.

PMID- 15463660
TI  - Hookworm larval infectivity, arrest and amphiparatenesis: the Caenorhabditis
      elegans Daf-c paradigm.
AB  - Arrested development dramatically alters the life history of some species of soil
      transmitted nematodes and elicits profound variations in the epidemiology of the
      infections they cause. Here, Peter Hotez, John Hawdon and Gerhard Schad show how
      an understanding of the cellular and molecular bases of arrested development may
      lead to new approaches for the control of ancylostomiasis and related infections.

PMID- 15463661
TI  - Seasonal changes in human immune responses to malaria.
AB  - Cellular as well as humorol immune responses to malaria antigens fluctuate in
      time in individuals living in molono-endemic areas, particularly where malaria
      transmission is seasonal. The most pronounced changes are seen in association
      with clinical attacks, but osymptomatic infection can also lead to apparent
      immune depression. However, recent data have shown that seasonal variation in
      cellular immune responses may occur even in the absence of detectable
      porositaemia. Here, Lars Hviid and Thor G. Theonder review the seasonal variation
      in human immune responses to malaria, and discuss its possible causes and
      implications.

PMID- 15463662
TI  - Entamoeba histolytica as a model for the primitive eukaryotic cell.
AB  - Entamoeba histolytica is a structurally simple eukaryote lacking mitochondria,
      peroxisomes and a well-developed Golgi apparatus, also in its biochemistry, it
      deviates substantially from the more complex eukoryotes. These features have
      alternatively been interpreted as archaic, ie. the ancestor of Entamoeba branched
      off before the primitive eukaryotic cell obtained proto-mitochondria, or as
      regressive, ie. Entamoeba has lost its mitochondria in the course of its
      adaptation to a parasitic life style. Tilly Bakker-Grunwald and Claudia Wostmann
      favor the first interpretation and discuss in which respects E. histolytica may
      serve as a model for the primitive eukaryote.

PMID- 15463663
TI  - Mechanistic approaches to quantitate anthelmintic absorption by gastrointestinal
      nematodes.
AB  - In this article, David Thompson, Norman Ho, Sandra Sims and Timothy Geary look at
      the problem o f quantitating drug absorption by gastrointestinal nematodes.

PMID- 15463665
TI  - Intestinal helminth expulsion.

PMID- 15463666
TI  - Thoughts on the entrapment of nematodes by fungi.

PMID- 15463668
TI  - Nemoglobins: divergent nematode globins.
AB  - Globins are proteins commonly associated with oxygen transport in vertebrate
      blood, but the invertebrate phyla display a wide variety of globin types that
      reflect their disparate life styles and evolutionary history. It has been known
      for over 100 years that parasitic nematodes contain globins, but recent molecular
      investigations are only now beginning to shed some light on their curious
      properties. Mark Blaxter here describes the diversity of the different globins
      found in nematodes, and reviews emerging data on their evolution and function.

PMID- 15463669
TI  - Naturally occurring antibodies that react with protozoan parasites.
AB  - In this paper, Eiji Konishi reviews general features of naturally occurring
      (natural) antibodies that react with protozoan parasites. Several functions of
      natural antibodies have been identified in relation to their multireactivity, but
      reports on protozoan infection have dealt mainly with the role of natural
      antibodies in the innate immunity of the host, These antibodies lyse cells in the
      presence of complement and have opsonizing activity, in vitro. Studies of their
      origin have shown the possibilities of (1) continuous polyclonal stimulation by
      gastrointestinal bacteria, and (2) there being multireactive antibodies secreted
      by CD5(+) B cells. The protective functions of natural antibodies are important
      in the interpretation of the host range, the mode of infection, and the course of
      the disease of certain protozoan parasites.

PMID- 15463670
TI  - Cell signalling and motility in Entamoeba histolytica.
AB  - Entamoeba histolytica crawls as a polarized cell following external stimuli, with
      the translocation of signals modifying extracellular matrix interactions and the
      amoeba cytoskeleton. Nancy Guillen here describes how the gliding of E.
      histolytica cells requires the activity of the actomyosin complex, and how
      actomyosin functions related to motility are necessary for pathogenesis and for
      amoebal escape from the host immune response.

PMID- 15463671
TI  - Target antigens for asexual malaria vaccine development.

PMID- 15463672
TI  - Biosynthesis of protein-linked oligosaccharides in trypanosomatid flagellates.
AB  - In this article, Armando Parodi presents a summary of the knowledge of the
      structure and biosynthesis of mammalian Asn-linked (N-linked) oligosacchorides
      and compares this with what is known in trypanosomatids.

PMID- 15463673
TI  - Do parasitic infections break T-cell tolerance and trigger autoimmune disease?
AB  - Burnet and Fenner originally defined 'tolerance' as 'unresponsiveness against
      self'. It is now generally accepted that the phenomenon of tolerance is required
      to protect on individual from potentially autoreactive cells. Recent experiments
      have independently shown that parasite infection or interleukin 2 (IL-2) can
      reverse an established T-cell tolerance in vivo. Breaking T-cell tolerance
      restores the capacity of T cells to be stimulated by their specific antigen and,
      in the case of a self-antigen, may be followed by autoimmune disease. In this
      review, Martin Rocken and Ethan Shevach briefly describe the potential pathways
      for generating T-cell tolerance in vivo, and focus on recently described
      mechanisms by which parasitic infections may circumvent or abrogate the tolerant
      state.

PMID- 15463674
TI  - The Trypanosoma cruzi ribosomal P protein family: classification and
      antigenicity.
AB  - The multi-copy ribosomal P proteins have been identified on the ribosomes of
      prokaryotic and eukaryotic cells, and their antigenicity is an important feature
      of human Trypanosoma cruzi infection. In this review, Mariano Levin, Martin
      Vazquez, Dan Kaplan and Alejandro Schijman give a rational basis for the
      classification of these proteins, and discuss their inter-relationship.

PMID- 15463675
TI  - A Sporozoite-based vaccine for Theileria parva.
AB  - East Coast fever, which is caused by Theileria parva infection in cattle, is of
      major economic importance in eastern and central Africa. Until recently, the only
      available method of immunization against East Coast fever was the infection with
      live sporozoites and simultaneous treatment with a long-acting oxytetracycline.
      This method has two major disadvantages: (I) it uses live organisms; and (2) the
      immunity engendered is parasite strain specific. In this article, Antony Musoke,
      Vishvonath Nene and Subhosh Morzoria review the progress made in developing an
      alternative method o f immunization based on a defined sporozoite antigen.

PMID- 15463676
TI  - Genome analysis of Theileria parva.
AB  - Recent technological developments in the field of genome analyses have advanced
      our knowledge of the structures of prokaryotic and eukoryotic genomes. Examples
      of these range from small bacterial genomes, such as Escherichia coli, to the
      more complex genomes of Caenorhabditis elegans, Drosophila, humans and mouse.
      Here, Subhash Morzona and John Young review developments in mapping the genome of
      on economically important protozoan parasite o f cattle, Theileria parva. This
      map provides a framework for more detailed analysis of the genome structure o f
      this organism. The methodologies developed in constructing the map also have
      application to the mapping of other protozoan genomes.

PMID- 15463677
TI  - Development of genetic systems for Toxoplasma gondii.
AB  - The protozoan parasite Toxoplasma gondii has recently emerged as an important
      opportunistic pathogen in humans. Toxoplasma also shares a number of biological
      features with Plasmodium and Eimeria, which are important pathogens of humans and
      animals. Because o f the ease o f experimental use, David Sibley, Elmer
      Pfefferkom and John Boothroyd have undertaken the development of genetics in
      Toxoplasma as a model intracellular parasite. Toxoplasma is presently the only
      parasitic protozoan where both classical and molecular genetics are feasible. The
      recent advances in this system are highlighted here, along with potential
      applications of genetics for understanding intracellular parasitism.

PMID- 15463678
TI  - The polyprotein allergens of nematodes.
AB  - Symptoms of infection with a number of parasitic nematodes may be associated with
      IgE antibody and associated immunopathologies. This has drawn attention to
      parasite allergens and provoked discussion on the wisdom of their inclusion in
      recombinant vaccines. Here, Larry McReynolds, Malcolm Kennedy and Murray Selkirk
      review work on a prominent set of allergens recently characterized in several
      nematode species.

PMID- 15463679
TI  - SCID mice as models for parasitic infections.
AB  - Mice with severe combined immunodeficiency (SCID mice) have become a favored
      model system for the study of many parasitic diseases. In this review, Samuel
      Stanley Jr and Herbert Virgin IV provide a brief overview of the biology of the
      SCID mouse, and review some examples of how the SCID mouse model has been applied
      to the study of the immunology of a number of different parasitic diseases.

PMID- 15463680
TI  - 200 Years of lice in Glasgow: an index of social deprivation.
AB  - Who gets lice? Using detailed health records of the citizens of Glasgow over the
      past couple of centuries, Steve Lindsay shows that lice have in the past been
      associated with deprivation. This conclusion may be controversial but, with the
      demise of the nit nurses and their detailed records, we are no longer in a
      position to say whether or not the same is true today.

PMID- 15463682
TI  - Metronidazole and drug resistance.

PMID- 15463683
TI  - Maternal filarial infection - a persistent risk factor for microfilaremia in
      offspring?
AB  - The observation that children born to mothers that are infected with Wuchereria
      bancrofti ore more susceptible to filarial infection than those born to
      uninfected mothers, raises many questions, particularly regarding immune
      mechanisms. In this article, Allen Hightower, Patrick Lommie and Mark Eberhard
      discuss these issues and their implications for the epidemiology of filarial
      infection.

PMID- 15463684
TI  - Inhibition of microsporidian spore germination.
AB  - Microsporidia are obligate intracellular parasites that are increasingly
      recognized as significant causes of disease in AIDS patients. Gordon Leitch,
      Govinda Visvesvara and Qing He here describe the deployment of the microsporidian
      spore infection apparatus, the polar filament, and show how this may be a useful
      site for chemotherapeutic interdiction of the infections caused by these
      parasites.

PMID- 15463685
TI  - Mechanisms of development of immunosuppression during Trypanosoma infections.
AB  - Acute infection with Trypanosoma cruzi or its African relatives, including T.
      brucei rhodesiense, T. b. gambiense, T. b. brucei and T. congolense, is
      frequently accompanied by manifestations of immunological dysfunction. Initially
      investigators catalogued the ensuing immunologic alterations and identified a
      number of modifications in lymphoid or accessory cell properties. More recently,
      the emphasis has switched towards the molecular underpinnings of
      immunosuppression in these infections. In this article, Marcelo Sztein and Felipe
      Kierszenboum focus on recent progress made in the quest to delineate the
      mechanisms behind altered lymphocyte functions in tryponosomal infections, point
      out particular and common features of immunosuppression induced by T. cruzi and
      African trypanosomes, and outline possible directions for future research.

PMID- 15463686
TI  - Nematophagous fungi: prospective biological control agents of animal parasitic
      nematodes?
AB  - The rapidly escalating problem of anthelmintic resistance and the increasing
      concerns of chemical residues in livestock products and the environment pose
      serious threats to the future of chemotherapeutic control o f animal parasitic
      nematodes. One possible non-chemotherapeutic approach is biological control using
      nemotophagous fungi. Although Gronvold and colleagues recently described their
      experiments with two nematode-destroying fungi, Arthrobotrys and Duddingtonia,
      this alternate control option has received relatively little research attention.
      Here, Peter Waller broadens the discussion to consider the fundamental problems
      and prospects of this non-chemotheropeutic control strategy.

PMID- 15463687
TI  - Hydatid disease in Western Australia: a novel approach to education and
      surveillance.
AB  - Hydatid disease (echinococcosis) remains a public health and economic problem of
      global proportion. Treatment usually requires major surgery and the prognosis for
      some forms of the disease is poor. The variable transmission patterns exhibited
      by the causative agents of this complex zoonosis, and inadequate support both
      internationally and nationally, have resulted in the establishment of control
      campaigns that are usually organized and funded at a local level. Here, Andrew
      Thompson, Ian Robertson, Robin Gasser and Clare Constantine describe a novel,
      targeted campaign of education and surveillance that has recently been initiated
      in Western Australia, where a totally artificial cycle of transmission for
      Fchinococcus granulosus has been established as a result of human activity.

PMID- 15463688
TI  - Feeding success of vectors on infected hosts.

PMID- 15463689
TI  - Alphavirus expression systems: applications to mosquito vector studies.
AB  - In this review, Steve Higgs, Ann Powers and Ken Olson describe how alphavirus
      expression systems, based on infectious cDNA clones of Sindbis virus, constitute
      a novel RNA virus delivery system suitable for the efficient expression of
      heterologous gene products or RNA sequences in mosquito cells or adult
      mosquitoes. The technique permits ready assessment of molecular genetic-based
      methods of intracellular interference to infection and provides a powerful new
      tool for molecular biological studies in arthropods.

PMID- 15463690
TI  - Neosporosis.
AB  - Neospora caninum is a recently recognized protozoan parasite of animals, which,
      until 1988, was misdiagnosed as Toxoplasma gondii. Neospora caninum or Neospora
      like parasites, here discussed by J.P. Dubey and David Lindsay, cause paralysis
      and death in dogs and neonatal mortality and abortion in cattle, sheep, goats and
      horses.

PMID- 15463691
TI  - The role of parasites in generating evolutionary novelty.
AB  - In this review, David Bermudes and Keith Joiner discuss the interrelationship
      between parasitism and mutualism and examine the parallel mechanisms used by
      parasites and mutualists to access and persist within the intracellular
      environment. By drawing analogies with mutualistic associations, they suggest
      mechanisms by which some parasites may ultimately benefit their hosts. They
      further speculate that some hosts may even become dependent upon their parasites.

PMID- 15463692
TI  - RAPD in the genus Trichinella.

PMID- 15463693
TI  - Potential eradication of taeniasis/cysticercosis.

PMID- 15463695
TI  - RNA processing in malarial parasites.
AB  - RNA processing in malarial parasites is a relatively new focus o f scientific
      research. Although only a few transcripts have been characterized in depth, a few
      patterns are beginning to emerge. Alexandra Levitt here reviews post
      transcriptional processing in Plasmodium.

PMID- 15463694
TI  - Feeding success of vectors on infected hosts: reply.

PMID- 15463696
TI  - The lipophosphoglycan of Leishmania and macrophage protein kinase C.
AB  - Lipophosphoglycan (LPG), the major cellsurface glycoconjugate of Leishmania
      promastigotes, is on essential virulence determinant. One feature of LPG resides
      in its strong inhibitory effect on the activity of purified protein kinase C
      (PKC). In this article, Albert Descoteaux and Salvatore Turco briefly review the
      evidence that LPG effectively inhibits PKC activity in the macrophage, and
      discuss the implication of such inhibition on Leishmania intramacrophoge
      survival.

PMID- 15463697
TI  - The role of insect growth regulators in arthropod control.
AB  - Insect growth regulators (IGRs) represent a relatively new category of insect
      control agents aimed mainly at covering the need for safer compounds and
      overcoming the development o f resistance to 'classical' insecticides. The
      various types of IGR are reviewed here by Jean-Francois Graf and their mechanism
      of action, their practical application and their respective advantages and
      limitations are discussed. A comprehensive assessment is made of current and
      future prospects for IGRs in insect and ectoparasite control.

PMID- 15463699
TI  - Migration, selection and population size in Ostertagia ostertagi.

PMID- 15463698
TI  - Does the negative binomial distribution add up?
AB  - The negative binomial distribution (NBD) is widely used to describe the
      distribution of parasitic helminths in a number of host individuals and has
      proved a useful, though possibly overused, empirical and theoretical device. It
      is therefore important that the limits to the applicability of the NBD be clearly
      defined. In this paper, Alan Grafen and Mark Woolhouse consider applications of
      the NBD in situations where either the host or parasite population can be divided
      into subpopulations of different types (eg. by age, sex or genotype), and they
      describe the relationships between the frequency distributions relevant to the
      different subpopulations and those relevant to the total population.

PMID- 15463700
TI  - Unravelling the cytokine network in Malaria.

PMID- 15463701
TI  - Trypanosomiasis of domestic animals in China.
AB  - Trypanosomiasis caused by Trypanosoma evansi (surra) is a problem of great
      economic importance in livestock in China because it affects important working
      animals: buffaloes in the south and east, and horses and cattle in the north and
      west. In addition, buffaloes are an important source of meat and leather for the
      Chinese population. In the north and west, T. evansi is found mainly in camels,
      whereas in the east, the south and the southwest, it is primarily buffaloes,
      cattle and horses that are affected by this parasitic flagellate. Although
      trypanosomiasis is one of the most important parasitic diseases of domestic
      animals in China, little information on this disease has been published. In this
      article Zhao-Rong Lun, Yuang Fang, Chang-Ji Wang and Reto Brun evaluate
      trypanosomiasis of domestic animals in China and review epidemiological studies
      of the past 40 years.

PMID- 15463702
TI  - Peritrophic membranes, cell surface molecules and parasite tropisms within
      arthropod vectors.
AB  - Parasite penetration of the arthropod midgut epithelium is, in many species,
      hindered or blocked by the peritrophic membrane. Having negotiated this, the
      parasite then must develop tropisms that ensure its survival. Here, Nick Miller
      and Mike Lehane summarize existing data on the molecular mechanisms of parasite
      vector interactions.

PMID- 15463703
TI  - Merozoite surface antigen-I of plasmodium.
AB  - The merozoite is the invasive form of the asexual stage of Plasmodium species. At
      least two polymorphic glycoproteins have been found on its surface in the human
      malaria parasite Plasmodium falciparum. The best-characterized of these is known
      as merozoite surface antigen-1 (MSA1) (185-200 kDa) (Ref. 1). Similar molecules
      are found in other malaria species. The other merozoite surface antigen, MSA2 (35
      48 kDa) (Ref. 2), is distinct from MSA1 but is equally polymorphic. In this
      review, Juan Cooper condenses the body of structural information on MSA1 known to
      date. A database compiled from MSA1 sequences from several species used together
      with sequence comparisons and predicted secondary structure reveals interesting
      features of this molecule.

PMID- 15463706
TI  - Unravelling the cytokine network in malaria: reply.

PMID- 15463705
TI  - Migration, selection and population size in ostertagia ostertagi: reply.

PMID- 15463707
TI  - Man and sea urchin - more closely related than African and American trypanosomes?

PMID- 15463708
TI  - Organic acid excretion by helminths.

PMID- 15463709
TI  - Clonality in leishmania.

PMID- 15463710
TI  - Toxoplasmosis - congenital and in immunocompromised patients: a parallel.
AB  - Toxoplasmosis is a protei form disease that is particularly severe in
      congenitally infected foetuses, after transplant surgery and in patients with
      AIDS. In this review, Pierre Ambroise-Thomas and Herve Pelloux describe and
      compare the epidemiology, pathophysiology and clinical features of these three
      different forms of the disease.

PMID- 15463711
TI  - The importance of mosaic genes to trypanosome survival.
AB  - African trypanosomes possess several elegant ways to evade the immune defenses o
      f mammalian hosts. They have an extensive repertoire o f genes for a variant
      surface antigen and recent data show that this finite repertoire can be further
      amplified by mosaic gene formation and point mutation, producing an almost
      limitless capacity to vary. The significance of these mechanisms of antigenic
      diversity to trypanosome biology and the parasite-host relationship in general
      are discussed here by Anthony Barbet and Sondra Kamper.

PMID- 15463712
TI  - Atovaquone - a novel broad-spectrum anti-infective drug.
AB  - Atovoquone is a novel hydroxynaphthoquinone that is currently showing clinical
      promise for the treatment of malaria and the AIDS-associated diseases
      Pneumocystis carinii pneumonia and toxoplosmosis. The drug is the end product of
      half a century of research by numerous groups who have investigated the
      ontiporositic properties of many related compounds. Atovaquone is the only member
      of the series to show therapeutic activity in humans when taken orally. In this
      article, Alan Hudson explores the background to the discovery of this drug and
      reviews its mode of action, and biological and clinical profiles.

PMID- 15463713
TI  - A new test for infection by Entamoeba histolytica.
AB  - Entamoeba histolytica is a common parasite of the human intestine, and in a
      significant percentage of cases it invades the tissues. Virulent strains of the
      organism produce the proteinose histolysain, which almost certainly facilitates
      the invasive behaviour. Histolysoin has been isolated, a selective assay
      developed, and specific antisera raised against the enzyme. As described here by
      Alfredo Luaces, Lyda Osorio and Alan Barren, the ENZYMEBA test for infection by
      E. histolytica combines the specificities of both antibodies and enzyme assay to
      achieve a high degree of sensitivity and selectivity. Circulating antibodies to
      histolysain were detected in a solid-phase enzyme immunoassay, the results
      suggesting that a humoral immune response is induced by histolysain during the
      formation of liver abscess.

PMID- 15463714
TI  - Improved immunodiagnostic tests to monitor onchocerciasis control programmes - a
      multicenter effort.

PMID- 15463715
TI  - Secretory processes in Plasmodium.

PMID- 15463716
TI  - Avermectins in arthropod vector management - prospects and pitfalls.
AB  - The proven impact of avermectins against a wide variety of arthropod vectors
      suggests that this new family of compounds holds promise in reducing the
      incidence of vector-borne disease. Experimentally, decreased survival and
      abundance of various vector species indicate that certain vector populations may
      be so manipulated. In addition, sublethal effects on individuals include
      lengthened development, decreased fecundity and diminished parasite uptake.
      Enthusiasm must be cautious, given possible impacts on non-target species and the
      eventual development of resistance. Here Mark Wilson emphasizes that the present
      challenge is to study how this new toxin may be integrated into vector-management
      schemes that already employ multiple, diverse interventions. Ultimately, the
      value of such action must be measured not simply in terms of reduced vector
      abundance, but also with the more complex equation of reduced parasite
      transmission in mind.

PMID- 15463717
TI  - Cellular biology of Cryptosporidium parvum.
AB  - With the emergence of Cryptosporidium parvum as a major pathogen encountered in
      human and veterinary clinical practice, a need for increased knowledge of the
      cellular- and immuno-biology of this Apicomplexan parasite has developed. Initial
      work has used paradigms taken from other Apicomplexans, especially Plasmodium,
      Toxoplasma and Eimeria, as a starting point. In this article, Carolyn Petersen
      discusses the observation that in these organisms, molecular targets of
      antibodies (which have protective value, in vivo, against disease) have
      frequently been located in the apical complex or on the surface of the invasive
      stages of the parasite and appear to mediate biologically crucial processes
      including motility, attachment to the host cell, modification of the host
      membrane, and entry into the host cell. Molecular-biology approaches to the study
      of enzymes and of structural proteins which mediate motility are also considered.
      Invasion mechanisms, biochemical pathways and motility may involve molecules that
      will prove susceptible to immunotherapeutic or chemotherapeutic interruption of
      cryptosporidiosis.

PMID- 15463718
TI  - Malaria proteases and red blood cell invasion.
AB  - Studies of malaria proteases have focused on two general groups, corresponding to
      activities specific to malaria parasites: (1) proteases involved in hemoglobin
      degradation which are active in the food vacuole and which exhibit optimal
      activity at low pH; and (2) proteases specific to schizonts and/or merozoites
      which are involved in merozoite maturation and red blood cell invasion and which
      exhibit optimal activity at neutral pH. In this paper, Catherine Braun Breton and
      Luis H. Pereira da Silva will focus on those activities necessary for the release
      of infectious merozoites and the entry of the parasite into its host cell.

PMID- 15463720
TI  - The use of electrophoretic profile of RNA to differentiate Tryponosoma brucei
      from T. congolense.

PMID- 15463719
TI  - Are antibodies important in mice infected with Plasmodium yoelii?

PMID- 15463721
TI  - Producer cells of interleukin 12.

PMID- 15463722
TI  - Secretory transport in Plasmodium.
AB  - The asexual blood stage of the human malaria parasite Plasmodium falciparum
      resides within the mature erythrocyte - a cell that has no intracellular
      organelles and few biosynthetic activities. However, Plasmodium, as on actively
      growing and dividing cell, has numerous requirements for the uptake o f nutrients
      and expulsion of waste. Hence, the parasite must extensively remodel the
      erythrocyte to facilitate its survival, not only by exporting numerous proteins,
      but also by providing the requisite machinery for their .trafficking. In this
      review, Heidi Elmendorf and Kastun Haldar propose a model for secretion in P.
      falciparum.

PMID- 15463723
TI  - Entamoeba, giardia and toxoplasma: clones or cryptic species?
AB  - The availability of molecular markers has renewed interest in the taxonomy of
      parasitic protozoa at the subspecific and specific levels. Nevertheless, the
      conclusions reached are heavily dependent upon the way the data are analyzed.
      Some authors have emphasized the value of genetic distances to propose the
      creation o f new species, while others have rather favoured a population genetic
      approach to account for the intraspecific variability of parasites. In this
      article, using three illustrative cases, Michel Tibayrenc shows that dissimilar
      taxonomic approaches can be built from quite comparable sets of data.

PMID- 15463724
TI  - Epidemiological evidence for an association between chloroquine resistance of
      Plasmodium falciparum and its immunological properties.
AB  - The appearance of chloroquine-resistant genotypes o f Plasmodium falciparum has
      thwarted the goal of global eradication of malaria. Although much effort has been
      put into understanding the molecular mechanisms of chloroquine resistance, many
      questions about its distribution remain open: Why, some 30 years after the
      emergence o f chloroquine resistance, have resistant genotypes not taken over the
      population? Why have many parasites remained sensitive? Why, after its first
      appearance in Africa, has chloroquine resistance spread so rapidly through sub
      Saharan Africa? In this paper Jacob Koella reviews epidemiological data that
      suggest that an answer to these questions may involve an association between
      chloroquine resistance and immunological properties o f malaria parasites.

PMID- 15463725
TI  - In vitro assays for the study of erythrocyte invasion by malarial parasites.
AB  - In vitro assays for the study o f erythrocyte invasion by merozoites are
      available for several primate and rodent malarial species. These assays are
      essential means by which potential anti-merozoite vaccine candidates are
      identified. John Dalton, John McNally and Susan O'Donovan describe the various
      types of invasion assays that are in current use, outline the procedures for
      performing these assays and add some pointers on interpretation of data derived
      from them.

PMID- 15463726
TI  - Allergic inflammation as a hypothesis for the expulsion of worms from tissues.

PMID- 15463727
TI  - Intermediary metabolism of Leishmania.
AB  - In the course of their existence, parasites develop several metabolic pathways
      that differ significantly from those of their hosts. Despite the fairly close
      evolutionary kinship between Leishmania donovani and Trypanosoma brucei, the
      forms that live in the insect vectors have evolved different strategies for the
      disposition of available food resources. In this brief review, Joseph Blum will
      focus on the data available from studies on Leishmania spp and will largely
      ignore the information available from Trypanosoma spp.

PMID- 15463728
TI  - ATP versus pyrophosphate: glycolysis revisited in parasitic protists.
AB  - It is generally assumed that glycolysis is remarkably similar among all
      organisms, prokaryotic and eukaryotic. This view has been extended to protists.
      However, there is growing evidence that significant deviations from conventional
      glycolysis occur in protists. Very different species, some parasitic, rely on
      peculiar enzymes that use pyrophosphate as substrate. In this review, Emmanuel
      Mertens describes such unusual pyrophosphate metabolism in parasitic protists.

PMID- 15463730
TI  - FCR-3, chloroquine resistance and cross-contamination of culture lines of
      Plasmodium falciparum.

PMID- 15463731
TI  - A mosquito net by any other name.

PMID- 15463733
TI  - Immunity to helminths.

PMID- 15463734
TI  - Protective immunity in lyme borreliosis.
AB  - Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common
      vector-borne illness in the USA. Although early infection can be treated with
      antibiotics, the initial diagnosis is difficult and late disease may be
      recalcitrant to therapy. A vaccine against Lyme disease is therefore needed, and
      murine models of Lyme borreliosis have facilitated its development. In this
      review, Erol Fikrig, Fred Kantor, Stephen Barthold and Richard Flavell focus on
      the use of Borrelia surface antigens as vaccine candidates for Lyme disease.

PMID- 15463735
TI  - 'Concealed' antigens: expanding the range of immunological targets.
AB  - For many parasites, the interaction between the immunogenicity of the parasite
      and the immunological response of the host is a dynamic equilibrium that allows
      both to survive, albeit often with severe consequences for the host. Vaccines, if
      intended as a means of parasite control, are unlikely to be generally successful
      if they do no more than mimic an immunological equilibrium that would be reached
      after natural exposure to the parasites. The situation must be tipped in favour
      of the host. It has been difficult to find ways around this impasse. One approach
      has been receiving practical attention over recent years, an approach that Peter
      Willadsen, Craig Eisemann and Ross Tellam have called vaccination against
      'concealed' antigens.

PMID- 15463736
TI  - The current status of Leishmania RNA virus I.
AB  - Viruses of Leishmania have recently been identified and characterized. These
      viruses are consistently double-stranded RNA viruses of approximately 5 kb. They
      have not been shown to exist outside their protozoan host, persistently infecting
      these parasites. The laboratory of jean Patterson has been interested in
      characterizing and identifying viruses of protozoans in order to use them as
      molecular probes of the unique gene expression mechanisms of protozoan parasites.

PMID- 15463737
TI  - Nematode-trapping fungi against parasitic cattle nematodes.
AB  - Interactions between larvae of bovine gastrointestinal nematode parasites and
      nematode-trapping fungi, such as Arthrobotrys and Duddingtonia species and
      strains have been studied in Denmark. In this article Jorn Gronvold, Jens
      Wolstrup, Peter Nansen and Svend Aage Henriksen discuss how these fungi are able
      to grow, trap and kill parasitic nematode larvae, both on agar in the laboratory
      and in cattle faeces in the field.

PMID- 15463738
TI  - Epithelial ion transport - possible contribution to parasite expulsion.
AB  - Multiple local effector mechanisms contribute to host protection from
      multicellular parasites. In this article, Alan Baird and Kate O'Malley describe a
      technique for voltage clamping isolated intestinal mucosae obtained from
      previously parasitized animals. Antigen challenge evoked an ion transport
      response which is the mechanism underlying net fluid secretion that may
      contribute to repulsion of enteric-dwelling parasites.

PMID- 15463739
TI  - Axenic culture of Leishmania amastigotes.
AB  - One of the future goals in Leishmania research will be to reproduce the entire
      life cycle oxenically, in vitro. In this article, Paul Bates reviews recent
      progress in the axenic culture of amastigotes and addresses some of the remaining
      problems associated with culture methods for both amostigote and promostigote
      forms.

PMID- 15463741
TI  - Mechanisms of drug resistance in Leishmania.
AB  - The emergence of drug resistance in protozoan parasites is a major obstacle to
      their control. Since vaccines are not yet in sight for several of these
      parasites, there is on urgent need to develop new and better drugs. These
      antimicrobial agents will possibly be more expensive, and will therefore impose
      on additional burden in health-care costs and in the planning of public health
      policies of the developing countries. A better understanding of drug resistance,
      to try to circumvent or overcome it, and the search for new specific cellular
      targets of parasites are warranted. The development, in vitro, of drug-resistant
      parasite cell lines has been instrumental in our understanding of the mechanisms
      of drug resistance in parasitic protozoans. Marc Ouellette and Barbara
      Popodopoulou here present on overview of the recent progress on the elucidation
      of mechanisms of drug resistance in the protozoan parasite Leishmania, selected
      under laboratory conditions.

PMID- 15463742
TI  - Ivermectin resistance.
AB  - In this review of ivermectin resistance, Wesley Shoop discusses the definition of
      resistance, catalogs all known cases of ivermectin resistance, argues that
      overmectins and milbemycins belong in the same action family, discusses the
      possibility of resistance in the filariae, and suggests that detection of
      ivermectin resistance is the area where future research is most needed.

PMID- 15463743
TI  - Resistance to anticoccidial drugs in fowl.
AB  - Resistance has been encountered wherever drugs have been used extensively for the
      control of parasitic infections. The poultry industry is dependent upon drugs for
      the control of coccidiosis, a major disease of chickens caused by protozoan
      parasites of the genus Eimeria. In modern poultry production, drugs are used
      prophylactically for the prevention of coccidiosis by including them in the diet.
      This has inevitably led to the development of resistance. We have been fortunate
      in that new drugs have become available to replace those to which resistance has
      developed, but this situation is unlikely to continue. The problem of drug
      resistance, discussed here by David Chapman, has provided impetus for the
      development of new approaches (such as vaccination) for the control of
      coccidiosis.

PMID- 15463744
TI  - Drug resistance in schistosomes.
AB  - Drug resistance in schistosomes is confined essentially to compounds of the
      hyconthone/oxamniquine family, since no documented case of resistance has so far
      been reported for the widely used drug praziquantel. The availability of strains
      of Schistosoma mansoni that are resistant to hyconthone and oxomniquine has
      permitted a detailed genetic and biochemical study of the mechanism of action of
      these compounds. Drugs must be activated by enzymatic esterification and this
      ultimately results in the production of an electrophilic moiety capable of
      alkylating DNA and other parasite macromolecules. As reviewed here by Donato
      Cioli, Livia Pica-Mattoccia and Sydney Archer, resistance is due to the loss of a
      drug-activating enzyme that is present in sensitive schistosomes and absent in
      resistant worms and in the mammalian hosts. Further study of this enzyme may
      yield valuable clues for drug design and for a basic understanding of parasite
      metabolism.

PMID- 15463745
TI  - Reduced resources applied to antimalarial drug development.
AB  - This statement was made in 1984 (Ref. I): 'The Agency for International
      Development (AID) announced a major breakthrough in the development of a vaccine
      against the most deadly form of malaria in human beings. The vaccine should be
      ready for use around the world, especially in developing countries, within five
      years.' Since then, the spending on development of drugs against malaria has been
      on the decline. Brian Schuster and Wilbur Milhous wonder. did we declare victory
      too soon? Wouldn't the prudent approach have been to look at vaccines and drugs
      as complementary techniques rather than alternative approaches?

PMID- 15463746
TI  - Malaria: living with drug resistance.
AB  - The epidemiological factors associated with the development and spread of drug
      resistant malaria have been recently explored by Wemsdorfer in a paper in which
      he looked at parasite-drug-human-vector interactions that affect the occurrence
      and dynamics of drug resistance. The question that decision-makers must be asking
      themselves, as we face the 21st century, is: how will we live with drug
      resistance? Allan Schapira, Peter Beales and M. Elizabeth Halloran are ideally
      placed to consider this question. Extracting lessons from the past, they focus on
      drug-resistant Plasmodium falciparum in Africa. They propose a mathematical
      model, which will improve the conceptual basis for policy decisions and which has
      implications for drug development as well as for malaria-control programmes.

PMID- 15463747
TI  - Occurrence, genetics and management of insecticide resistance.
AB  - A lot has been learned about insecticide resistance in the past 40 years. The
      problem is more extensive and widespread than could have been predicted. In this
      review, Richard Roush discusses the genetics and management of resistance to
      insecticides (especially as related to arthropod vectors of human and animal
      diseases), with the objective of suggesting future directions.

PMID- 15463748
TI  - Modification of arthropod vector competence via symbiotic bacteria.
AB  - Some of the world's most devastating diseases are transmitted by arthropod
      vectors. Attempts to control these arthropods are currently being challenged by
      the widespread appearance of insecticide resistance. It is therefore desirable to
      develop alternative strategies to complement existing methods of vector control.
      In this review, Charles Beard, Scott O'Neill, Robert Tesh, Frank Richards and
      Serap Aksoy present an approach for introducing foreign genes into insects in
      order to confer refractoriness to vector populations, ie. the inability to
      transmit disease-causing agents. This approach aims to express foreign anti
      parasitic or anti-viral gene products in symbiotic bacteria harbored by insects.
      The potential use of naturally occurring symbiont-based mechanisms in the spread
      of such refractory phenotypes is also discussed.

PMID- 15463749
TI  - Metronidazole and drug resistance.
AB  - In recent years, the basis of metronidozole resistance has been examined in
      anaerobic protozoa, such as Trichomonas and Giardia, as well as anaerobic
      bacteria, such as Bacteroides and Clostridium. In this review, Patricia Johnson
      looks at a variety of mechanisms that lead to reduced susceptibility of these
      pathogens to the drug. The frequent correlation between metronidozole resistance
      and inefficient drug activation suggests that this is the level at which drug
      resistance operates.

PMID- 15463750
TI  - Drug resistance and Giardia.
AB  - Giardiasis is a worldwide disease that can cause serious morbidity. Metronidozole
      is the current recommended drug for treatment, and is mostly still effective.
      However, Giardia duodenalis, the causative agent, is capable of developing
      resistance to high levels of metronidozole and other drugs, in vitro, via a
      number of mechanisms. Resistance, in vivo, has been reported and many cases of
      treatment failure have been variously attributed to a number of causes, including
      resistance. Here, Jacqueline and Peter Upcroft ask: is this the beginning of
      another chapter of drug resistance? or is the situation likely to remain as a
      'few refractory cases'? Should we wait to find out or can we act positively to
      avert the possibility of yet another valuable drug in our limited pharmacopoeia
      becoming obsolete?

PMID- 15463752
TI  - CD8+ T cells and immunity to intracellular pathogens.

PMID- 15463751
TI  - Resistance to clinical drugs in African trypanosomes.
AB  - Drug resistance in African trypanosomes continues to confound clinicians and to
      stymy development o f equatorial Africa, taking its toll in lives and economic
      development. Drugs in current, widespread use have been employed continuously for
      over 60 years in some instances. The recent studies of Fairlamb and colleagues
      have outlined a defective purine-transport system in drug-resistant trypanosomes,
      which appears to explain resistance to several established tryponocides and
      suggests a guide for the development of new drugs. The recently developed agent
      dl-alpha-di fluoromethylornithine (DFMO) is effective against West African, but
      not East African, disease and its activity may be the result of the unregulated
      synthesis of S-odenosylmethionine in tryponosomes. In this report, Cyrus Bacchi
      outlines recent developments in the elucidation of mechanisms of resistance to
      established drugs and naturally occurring resistance to DFMO.

PMID- 15463753
TI  - Trypanosoma cruzi infection in women.

PMID- 15463754
TI  - The flagellar pocket of trypanosomatids.
AB  - The surface of the trypanosomatid forms the interface between the parasite and
      its host, and has evolved to repel a variety of host anti-microbial defences. The
      flagellar pocket constitutes a highly differentiated region of the trypanosomatid
      surface that facilitates internalization of host macromolecules, while
      restricting host access to the exposed, endocytic receptors of the parasite. In
      this review, Paul Webster and David Russell discuss the ability of this organelle
      to accumulate efficiently nutrients obtained from the host as a major factor in
      the success of this group of parasites.

PMID- 15463755
TI  - Glucose and proline transport in kinetoplastids.
AB  - The parasitic protozoa belonging to the kinetoplastids can use both sugars and
      amino acids as carbon and energy sources. In this review, Benno ter Kuile
      discusses nutrient acquisition and utilization and how the metabolic strategies
      reflect the environment encountered in host and vector. Recent genetic and
      physiological evidence suggests that facilitated diffusion may be the primary
      uptake mechanism for glucose, and possibly for proline as well, even though there
      is biochemical and genetic evidence suggesting that active transport occurs, if
      not across the plasma membrane, then across the membranes of organelles.
      Trypanosoma brucei seems to have a metabolic strategy that strives for maximum
      energy efficiency, making no storage materials and thereby limiting the control
      over its internal conditions. On the other hand, Leishmania donovani does create
      a storage buffer, entrapping glucose in the cell. In this manner, it maintains
      constant internal conditions at the expense of energy, enabling it to survive
      more adverse conditions in the macrophage and in its vector.

PMID- 15463756
TI  - Malaria sporozoites: survival, transmission and disease control.
AB  - A basic fact in malariology is that human malaria infections result from the bite
      of an infective anopheline mosquito. Without sporozoite transmission there is no
      malaria. Here, John Beier highlights our understanding of sporozoite biology from
      the perspective of how sporozoites develop and survive in mosquitoes, how they
      are transmitted during bloodfeeding, and how key elements in sporozoite-vector
      relationships present new opportunities for tackling critical questions relevant
      for disease control.

PMID- 15463758
TI  - Science of economics.

PMID- 15463759
TI  - Resistance genes at the population level.

PMID- 15463760
TI  - Surface properties, pathogenicity and differentiation of Entamoeba histolytica.

PMID- 15463761
TI  - Mosquito nets or bednets?

PMID- 15463763
TI  - Trypanosoma cruzi trans-sialidase and cell invasion.
AB  - Trypanosoma cruzi does not synthesize sialic acid but does contain a trans
      sialidase, an enzyme capable of transferring sialic acid between host
      glycoconjugates and the parasite. Sialic acids are negatively charged
      carbohydrates attached to the terminal non-reducing end of glycoproteins and
      glycolipids, and their presence can dramatically influence many cell-surface
      recognition processes. Since sialic acids have been implicated in several ligand
      receptor interactions, including the interaction of pathogenic viruses, bacteria
      and protozoans with their hosts, the expression of trans-sialidase and the
      acquisition of sialic acid by T. cruzi may be relevant to the interaction of the
      parasite with the host, and consequently may influence the pathobiology of Chagas
      disease. In this review, Sergio Schenkman and Daniel Eichinger discuss recent
      data about the structure and function of T. cruzi trans-sialidase.

PMID- 15463764
TI  - Sialidases from African trypanosomes.

PMID- 15463765
TI  - Encystation in Entamoeba invadens.
AB  - Knowledge of the biology and pathogenesis of the human parasite Entamoeba
      histolytica has been limited by the lack of efficient procedures to induce axenic
      encystation in the laboratory. However, such methods have been developed for E.
      invadens, a reptilian parasite, for which encystation can be induced by
      mechanisms that are as yet poorly defined. This has allowed the analysis of some
      morphological, physiological and biochemical events that accompany
      differentiation into cysts. Elucidation of these changes will lead to a better
      understanding of the process and therefore to the possibility of controlling it.
      Here, Everardo Lopez-Romero and Julio Cezar Villagomez-Castro emphasize the
      metabolism of cyst-wall polymers as a potential target to inhibit cyst formation
      with specific drugs that would be in principle, harmless to the host.

PMID- 15463766
TI  - ELISAs for parasitologists: or lies, damned lies and ELISAs.
AB  - The introduction in 1971, by Engvoll and Perlmann, of enzyme labels in
      immunoassays represented a significant technical advance. Their enzyme-linked
      immunosorbent assay (ELISA) proved to be as sensitive as radioimmunoossoys but
      safer to use. Since then, ELISAs have been widely used in the assay o f anti
      bodies and antigens. In this article, Pradhib Venkateson and Derek Wokelin focus
      on some o f the problems associated with ELISAs when applied to parasitic
      infections, which can modify antibody responses, by immunosuppression or
      polyclonal activation. The article also considers optimization, which is an
      essential step in the establishment o f on ELISA.

PMID- 15463767
TI  - Protection against malaria by thalassaemia and haemoglobin variants.
AB  - Recent epidemiological evidence has given increasing support to Haldane's 1949
      hypothesis that heterozygotes for such genetic disorders as thalassaemia might be
      protected against malaria, hence explaining the high gene frequencies for such
      disorders in endemic areas. As discussed here by Yongyuth Yuthavong and Prapon
      Wilairat, the possible cellular mechanisms, although still unclear, are emerging
      from in vitro studies which increasingly point to the importance of immune
      clearance mechanisms in some cases (such as alpha-thalassaemia and haemoglobin
      E). In other situations, decreased survival of the intra-erythrocytic parasite or
      decreased parasite invasion of the variant red blood cells may explain the
      protective effect. Whatever the cellular mechanisms are, the ultimate decisive
      factor is the relative fitness of the infected variant host, which may not be
      simply extrapolated from the cellular studies.

PMID- 15463768
TI  - The Phylogeny of malaria: a useful study.
AB  - Phylogenetic analyses allow an inference of the origins and evolutionary
      relationships between organisms. Andy Waters, Des Higgins and Tom McCutchan here
      discuss the benefits of an accurate understanding of these origins and
      relationships for malaria parasites to the modern fields of vaccine development,
      pathology and epidemiology.

PMID- 15463770
TI  - The current status of blastocystis hominis.

PMID- 15463769
TI  - Biochemical characterization within the genus Trichinella.

PMID- 15463771
TI  - Chitinase: a novel target for blocking parasite transmission?
AB  - In many species of blood-sucking arthropod, the internal tissues are covered by
      chitinous material that may hinder parasite invasion. To circumvent this
      potential barrier, therefore, parasites have developed mechanisms that involve
      the enzyme chitinase. In this review, Mohammed Shohobuddin and David C. Kaslow
      examine the relationship between chitinase and parasite transmission.

PMID- 15463772
TI  - Leishmania and Sandflies: interactions in the life cycle and transmission.
AB  - Leishmania infections in the vector sandfly are limited to the gut, where contact
      with tissues, secretions and the medium of sandfly food influence their cycle of
      development The parasites cope with and exploit their habitat by generating
      products that impair the function and damage the tissues of the gut In this
      review, Yosef Schlein concentrates on some of the recent advances in the limited
      knowledge of these parasite-vector interactions.

PMID- 15463773
TI  - The worm and the protozoa: stereotyped responses or distinct antigens?
AB  - Studies of parasitic diseases have provided the best in vivo correlates of the
      division of CD4+ helper T cells into distinct functional phenotypes, designated
      T(H)I and T(H)2, that mediate the balanced regulation of cellular and humoral
      immunity. In this article, Steven Reiner and Richard Locksley focus on why
      parasitic infections tend to generate such clearly polarized responses and
      emphasize that early events that mediate maturation signals towards T(H)1- or
      T(H)2-effector and memory cells remain incompletely defined. Effective
      vaccination that seeks to mold the developing immune response will need to
      consider the role of interleukins and various cell-surface molecules that have
      been identified, thus far, to influence CD4 subset differentiation.

PMID- 15463774
TI  - A method for collecting large quantities of Cryptosporidium parasites.
AB  - The intestinal mucoso may be regarded as a potential and abundant source of
      Cryptosporidium parvurn parasites from which all developmental stages might be
      collected. If intracellular stages could be recovered from the brush border, many
      of the limitations concerned with the use of oocysts and in vitro cultures may be
      overcome. Hans-Michael Muller, Lorella Ranucci, Edoordo Pozio and Andrea Crisonti
      discuss here how this can be done.

PMID- 15463775
TI  - Molecular methods for the detection and classification of Cryptosporidium.
AB  - Cryptosporidiosis is a zoonotic disease caused by a parasitic protozoan belonging
      to the coccidial genus Cryptosporidium. Current laboratory methods are adequate
      for the detection of the infection when oocysts are present in great numbers, but
      more-sensitive means of identification are urgently required. In a recent issue
      of Parasitology Today, Carolyn Petersen has presented a review of the cell
      biology of this parasite'. Here, Kath Webster draws attention to the various
      methods involved in its detection and classification.

PMID- 15463776
TI  - Distribution of tsetse and ticks in Africa: past, present and future.
AB  - The current concern over the effects of global warming has rekindled interest in
      the neglected topic of vector distribution. In order to predict the future,
      however, we must first comprehend the past and present. In this review, David
      Rogers and Sarah Randolph discuss the alternative biological and statistical
      approaches to understanding the present-day distributions of vectors, and make
      predictions about how these might change with global warming.

PMID- 15463778
TI  - Chloroquine-resistant Plasmodium falciparum and the MDR phenotype.

PMID- 15463777
TI  - Mathematical models of tick-borne disease transmission.

PMID- 15463779
TI  - Protection, pathogenesis and phenotypic plasticity in Plasmodium falciparum
      malaria.
AB  - Why does Plasmodium falciparum cause severe illness in some but not all
      infections? How is clinical immunity acquired? These questions have intrigued
      investigators since the clinical epidemiology of malaria was first described. The
      search for answers to both questions has highlighted the changes that take place
      at the surface of infected red blood cells during the last half of the
      erythrocytic cycle. These changes specify the antigenic and adhesive or
      cytoadherence phenotypes for the infected cell. Now the antigenic and adhesive
      phenotypes appear to be linked and together undergo clonal variation. In this
      article David Roberts, Beverley-Ann Biggs, Graham Brown and Christopher Newbold
      explain how clonal phenotypic variation and the linkage between adhesive and
      antigenic types contribute to our understanding of naturally acquired immunity
      and of pathogenesis of severe malaria.

PMID- 15463780
TI  - Opening the can of worms: molecular analysis of schistosome populations.
AB  - The Schistosomatidae are dioecious digenean parasites of the blood vascular
      system of vertebrates. Of the 13 genera within the family, only Sehistosoma is
      associated with humans and, of the mammalian blood flukes, this genus has
      achieved the greatest geographical distribution and diversification in terms of
      recognized species and definitive hosts parasitized. In this review, Dave
      Johnston, Emmanuel Dias Neto, Andy Simpson and David Rollinson consider some
      recent molecular research that either sheds light on the micro-evolutionary
      changes occurring within schistosome populations or provides insights into
      broader, macro-evolutionary questions.

PMID- 15463781
TI  - Recrudescence of Toxoplasma infection.

PMID- 15463782
TI  - Entamoeba dispar?

PMID- 15463785
TI  - Speciation and clonality in Entamoeba histolytica.

PMID- 15463783
TI  - Mathematical models of tick-borne disease transmission: reply.

PMID- 15463786
TI  - Molting, enzymes and new targets for chemotherapy of Onchocerca volvulus.
AB  - Parasitic nematodes do not multiply in definitive hosts, but they do molt, grow
      and mature for a certain period after infection, after which they devote their
      energies almost entirely to egg production. In this review, Sara Lustigman
      describes key metabolic enzymes that are essential to the development of the
      larval stages of Onchocerca volvulus in the host, making them potential
      therapeutic targets.

PMID- 15463787
TI  - The involvement of hemozoin toxicity in depression of cellular immunity.
AB  - Human monocyte-derived macrophages are severely impaired after ingestion of
      isolated malaria pigment (hemozoin) or hemozoin-containing red blood cells'. In
      this brief review, Franco Turrini, Evelin Schwarzer and Poolo Arese discuss
      possible pothophysiologicol consequences, outline unresolved problems and provide
      an outlook for future research.

PMID- 15463788
TI  - The major merozoite surface protein as a malaria vaccine target.
AB  - Experts gathered for two days in the summer of 1992 at the National Institutes of
      Health and the Walter Reed Army Institute of Research to discuss the potential of
      a major merozoite surface protein (MSP-1) in malaria vaccine development. The
      participants came in an exemplary spirit of co-operation, sharing ideas and
      unpublished data toward the common goal of a malaria vaccine. Their conclusions
      are presented here by Carter Diggs, Ripley Bollou and Lou Miller.

PMID- 15463789
TI  - PCR and strain identification in Plasmodium falciparum.
AB  - Anyone who has cultured Plasmodium falciparum is aware that confusion about the
      identity of commonly used strains, and inadvertent contamination of one strain
      with another have been persistent problems. These issues have been recently
      reviewed by Robson and colleagues. Jason Wooden, Susan Kyes and Carol Hopkins
      Sibley have recently adapted two methods that offer a quick, easy alternative for
      the identification of P. falciparum strains in the laboratory.

PMID- 15463790
TI  - A pocket chart to estimate true Schistosoma mansoni prevalences.
AB  - In a recent paper, Sake de Vlas and Bruno Gryseels have explored the extent and
      implications of the underestimation of Schistosoma mansoni prevalences, as
      measured by faecal screening. Together with Gernt van Oortmorssen, Anton
      Polderman and Dik Habbema, they now present a practical and generally applicable
      chart to infer 'true' prevalences from simple egg count surveys.

PMID- 15463791
TI  - MIF as a GST.

PMID- 15463792
TI  - Conservation of surface molecules in the trypanosomatids.

PMID- 15463793
TI  - The occurrence, role and evolution of chromatin diminution in nematodes.
AB  - Chromatin diminution takes place in presomatic cells of some parasitic nematodes
      during early development. This phenomenon may play an important role in somatic
      cell differentiation, since the somatic cells of these species undergo an
      extensive genome reorganization during development via chromatin diminution and
      polyploidization, as explained here by Clara Goday and Sergio Pimpinelli.

PMID- 15463794
TI  - Practical progress and new drugs for changing patterns of leishmaniasis.
AB  - The problems surrounding leishmaniasis are changing. An increase in travel, the
      Indian and Sudanese epidemics of visceral leishmaniasis, parasite resistance to
      antimony and the emergence of AIDS-related leishmaniasis have all increased the
      urgency for new drugs, and led to reappraisals of the old ones, as discussed here
      by Piero Olliaro and Anthony Bryceson.

PMID- 15463795
TI  - Pharmacokinetic disposition of benzimidazole drugs in the ruminant
      gastrointestinal tract.
AB  - Orally administered benzimidazole (BZ) drugs are ideally deposited in the rumen
      where they associate extensively with particulate digesta material, the residence
      time of this drug-digesta complex being a major influence on the subsequent rate
      and duration of BZ availability. This duration is shortened if the dose should
      bypass the rumen due to oesophageal groove closure. Benzimidazole metabolites
      flow from the rumen primarily in association with particulate digesta. In the
      abomasum, the majority of soluble metabolites result from gastric secretions.
      These metabolites flow into the small intestine where they are absorbed into the
      systemic circulation. Depending on the chemical structure a significant portion
      are secreted in bile either in a free (ie. unconjugated) or conjugated form. Free
      biliary metabolites are absorbed from the upper small intestine whereas bacteria
      in the large intestine hydrolyse the conjugated biliary metabolites to promote
      further absorption. Biliary derived metabolites are enterohepatically recycled
      but contribute little to the peripheral plasma metabolite pool. In this review,
      Des Hennessy discusses these issues in relation to the pharmacology of BZ drugs
      in the gastrointestinal tract of ruminants.

PMID- 15463796
TI  - More on unravelling the cytokine network in malaria.

PMID- 15463797
TI  - 'Concealed' antigens: expanding the range of immunological targets.

PMID- 15463798
TI  - Antimalarial resistance and health policies.

PMID- 15463799
TI  - Toxoplasmosis: the first commercial vaccine.
AB  - Infection with Toxoplasma gondii can have serious consequences in pregnant women
      and in immunocompromised individuals. For the farming industry it is a major
      cause of economic loss through neonatal mortality, particularly in sheep. In the
      following short review, David Buxton summarizes the main features of the complex
      immune response to the parasite and outlines how the first commercial vaccine was
      developed to control toxoplasmosis in pregnant sheep. Although the vaccine is
      inappropriate for use in human beings, the manner in which it induces immunity in
      sheep will prove vital to our understanding of the infection and the eventual
      development of a suitable vaccine to combat toxoplasmosis in people as well as in
      animals.

PMID- 15463800
TI  - Development of a vaccine against haemonchus contortus.
AB  - Haemonchus contortus is an economically important nematode parasite of sheep and
      the occurrence worldwide of strains resistant to anthelmintic chemicals has
      emphasized the need to develop a vaccine against it. Here, Ed Munn describes the
      approach to this problem adopted in his laboratory. The principle developed
      should be applicable to other gastrointestinal parasites.

PMID- 15463801
TI  - 5-Hydroxytryptamine and motility in Fasciola hepatica.
AB  - The study motility in Fasciola has been practically very difficult. 5
      Hydroxytryptamine (5-HT) has a strong stimulatory action on Fasciola movement,
      increasing both the amplitude and frequency of contractions, but most of the
      evidence for a transmitter role of 5-HT at the neuromuscular junction comes from
      fairly elementary pharmacological and neurochemical studies. As discussed here by
      Lindy Holden-Dye and Robert Walker, it still remains to be established that the
      effect of 5-HT on motility is mediated by 5-HT receptors actually present on the
      muscle cells. Analysis of the transmitter role of 5-HT and the delineation of the
      receptor type(s) involved in its stimulatory action will require the application
      of molecular techniques such as patch clamping of muscle cells, and cloning,
      sequencing and expression of 5-HT receptor complementary DNAs.

PMID- 15463802
TI  - Patch-clamp and chloride channels in Ascaris suum.
AB  - Single-channel electrophysiology is an invaluable tool fo the study of ion
      channels. However, it is a technique that has failed to attract widespread use by
      parasitologists. Here, Diane Dixon and Richard Martin outline the principles
      undelrying single channel recording and highlight its uses in the discovery of a
      new and unusual chloride channel in the musculature of Ascaris suum.

PMID- 15463804
TI  - CF or not CF? That is the question.

PMID- 15463805
TI  - Effects of pregnancy on health: certain aspects of importance for women with
      cystic fibrosis.
AB  - More women with cystic fibrosis (CF) now reach reproductive age and wish to
      become pregnant. Although women with CF have reduced fertility, many of them can
      become mothers. A pregnancy ought to be carefully planned since several studies
      have shown that pregnancy is well tolerated if good medical care is provided, and
      the CF woman is in a stable good condition. A short review of the implications of
      pregnancy for women with CF is presented. A suggested schedule for pregnant women
      with CF is given.

PMID- 15463806
TI  - The cystic fibrosis transmembrane conductance regulator: an intriguing protein
      with pleiotropic functions.
AB  - Cystic fibrosis is a frequent autosomal recessive disorder that is caused by the
      malfunctioning of a small chloride channel, the cystic fibrosis transmembrane
      conductance regulator. The protein is found in the apical membrane of epithelial
      cells lining exocrine glands. Absence of this channel results in imbalance of ion
      concentrations across the cell membrane. As a result, fluids secreted through
      these glands become more viscous and, in the end, ducts become plugged and
      atrophic. Little is known about the pathways that link the malfunctioning of the
      CFTR protein with the observed clinical phenotype. Moreover, there is no strict
      correlation between specific CFTR mutations and the CF phenotype. This might be
      explained by the fact that environmental and additional genetic factors may
      influence the phenotype. The CFTR protein itself is regulated at the maturational
      level by chaperones and SNARE proteins and at the functional level by several
      protein kinases. Moreover, CFTR functions also as a regulator of other ion
      channels and of intracellular membrane transport processes. In order to be able
      to function as a protein with pleiotropic actions, CFTR seems to be linked with
      other proteins and with the cytoskeleton through interaction with PDZ-domain
      containing proteins at the apical pole of the cell. Progress in cystic fibrosis
      research is substantial, but still leaves many questions unanswered.

PMID- 15463807
TI  - Subclinical anaemia of chronic disease in adult patients with cystic fibrosis.
AB  - Patients with chronic hypoxaemia develop secondary polycythaemia that improves
      oxygen-carrying capacity. Therefore, normal haemoglobin and haematocrit values in
      the presence of chronic arterial hypoxaemia in cystic fibrosis constitute
      'relative anaemia'. We sought to determine the cause of this relative anaemia in
      patients with cystic fibrosis. We studied haematological indices and oxygen
      saturation in healthy volunteers (n=17) and in adult patients with cystic
      fibrosis (n=15). Patients with cystic fibrosis had lower resting arterial oxygen
      saturation when compared with normal volunteers (P<0.0001), and exercise led to a
      greater reduction in arterial oxygen saturation (P<0.0001). However, haemoglobin
      and haematocrit values in patients with cystic fibrosis did not significantly
      differ from normal volunteers. Serum iron (P=0.002), transferrin (P=0.02), and
      total iron-binding capacity (P=0.01) were lower in patients with cystic fibrosis.
      There were no significant differences in serum ferritin, percentage iron
      saturation, serum erythropoietin or red cell volume between the groups. The data
      presented demonstrate a characteristic picture of anaemia of chronic disease in
      adult patients with cystic fibrosis, except for normal haemoglobin and
      haematocrit values. Normal haemoglobin and haematocrit values in patients with
      cystic fibrosis appear to represent a combination of the effects of arterial
      hypoxaemia promoting polycythaemia, counterbalanced by chronic inflammation
      promoting anaemia of chronic disease.

PMID- 15463808
TI  - Hypertonic saline and recombinant human DNase: a randomised cross-over pilot
      study in patients with cystic fibrosis.

PMID- 15463809
TI  - Successful pregnancy and delivery in a young woman with cystic fibrosis and
      gestational diabetes.
AB  - We describe a 23-year-old Delta F508 homozygote cystic fibrosis primigravida. At
      the onset of gestation, she had mild to moderate pulmonary involvement, exocrine
      pancreatic insufficiency, focal biliary cirrhosis, satisfactory nutritional
      status and normal fasting and post-prandial glucose blood levels. At 29 weeks,
      she developed polyhydramnion and gestational diabetes. At 37 weeks, she was
      delivered of a live 2,980 g boy by caesarean section under epidural anaesthesia.
      Insulin was subsequently discontinued and her pulmonary function improved
      spontaneously. Neither maternal nor neonatal health problems were observed during
      the 3-month follow-up.

PMID- 15463810
TI  - Optimising nutrition in cystic fibrosis.

PMID- 15463811
TI  - Nutrition in patients with cystic fibrosis: a European Consensus.
AB  - This document is the result of an European Consensus conference which took place
      in Artimino, Tuscany, Italy, in March 2001 involving 33 experts on nutrition in
      patients with cystic fibrosis, organised by the European Cystic Fibrosis Society,
      and sponsored by Axcan-Scandipharm, Baxter, Dr Falk Pharma, Fresenius, Nutricia,
      SHS International, Solvay Pharmaceuticals (major sponsor). The purpose of the
      conference was to develop a consensus document on nutrition in patients with
      cystic fibrosis based on current evidence.

PMID- 15463812
TI  - Immunopathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease
      mediated by an allergic late-phase inflammatory response to Aspergillus fumigatus
      antigens. ABPA is characterized by markedly elevated Aspergillus-specific and
      total IgE levels and eosinophilia, and manifested by wheezing, pulmonary
      infiltrates, and bronchiectasis and fibrosis, which afflict asthmatic and cystic
      fibrosis (CF) patients. We propose that ABPA develops in genetically susceptible
      CF patients due to HLA-DR2 and DR5 restriction, increased sensitivity to IL-4
      stimulation, and increased A. fumigatus allergen-specific Th2 CD4+ T-cell
      mediated responses. In addition, A. fumigatus proteases play a role in
      facilitation of antigen transport across the epithelial cell layer by damaging
      the epithelial integrity and by a direct interaction with epithelial cell surface
      receptors, resulting in pro-inflammatory cytokine production and corresponding
      inflammatory responses.

PMID- 15463813
TI  - Pilot safety study of liposomal prostaglandin (PGE1) in respiratory exacerbations
      in cystic fibrosis.
AB  - BACKGROUND: A pilot evaluation to assess the safety and possible benefits of TLC
      C-53, (prostaglandin E(1) associated with egg phosphatidylcholine liposomes) in
      acute respiratory exacerbations in children with cystic fibrosis (CF). METHODS:
      Randomised, double-blind, placebo-controlled study in 20 P. aeruginosa colonised
      patients. All received intravenous antibiotics. Subjects were given a rising dose
      of TLC C-53 (0.15-1.8 microg/kg) by 4 x 1-h infusions. Primary outcome measures
      were sputum IL-6, IL-8 and sputum neutrophil elastase. The rate of decline in
      lung function was determined at 6 weeks post-therapy as was the interval until
      the next respiratory exacerbation requiring intravenous antibiotic therapy.
      RESULTS: Analysis of primary and secondary outcome measures failed to show any
      significant differences between the two groups, although trends favoured the
      treated group. Decline in lung function over 6 weeks favoured the TLC C-53 group
      (FEV(1) mean difference 4.3%, 95% CI=-6.8, 15.4%). Time to next exacerbation also
      favoured the TLC C-53 group with a mean time to exacerbation for TLC C-53 of 26.0
      weeks against 11.9 weeks. CONCLUSIONS: A larger multi-centre trial of TLC C-53 as
      an adjunct to antibiotic therapy in respiratory exacerbations in CF would appear
      warranted.

PMID- 15463814
TI  - Fate of swallowed interleukin 8 and TNF alpha, and effect on the Wistar rat gut.
AB  - To evaluate the passage of cytokines through the gastrointestinal tract, we
      investigated the digestion of interleukin-8 (IL-8) and tumour necrosis factor
      alpha (TNF alpha), in vitro and in vivo, and their propensity to induce
      intestinal inflammation. We serially immuno-assayed IL-8 and TNF alpha solutions
      co-incubated with each of three pancreatin preparations at pH 4.5 and pH 8. We
      gavaged IL-8, TNF alpha and marker into 15 Wistar rats, and measured their faecal
      cytokine concentrations by ELISA and histologically examined their guts. IL-8
      immunoreactivity was extinguished by all pancreatin preparations after 1 h of
      incubation at 37 degrees C. TNF alpha concentration progressively fell from 1 to
      4 h with all enzyme preparations. Buffer control samples maintained their
      cytokine concentrations throughout incubation. No IL-8 or TNF alpha was detected
      in any rat faecal pellets. There was no significant proinflammatory effect of the
      gavaged cytokines on rat intestine. IL-8 and TNF alpha in aqueous solution could
      well be fully digested in the CF gut when transit time is normal and exogenous
      enzymes are provided, although cytokines swallowed in viscous sputum may be
      protected from such digestion.

PMID- 15463815
TI  - Chronic mucoid Pseudomonas aeruginosa cholangitis complicating ERCP in a CF
      patient.
AB  - We report a case of P. aeruginosa cholangitis in an adult with cystic fibrosis
      (CF). The patient had a past history of cholecystectomy and a new finding of
      intrahepatic biliary duct stricture. Evaluation and treatment with endoscopic
      retrograde cholangiopancreatography (ERCP) and percutaneous biliary tract
      drainage was complicated by post-procedure pain and fever. The only organism
      recovered from biliary drainage was P. aeruginosa. Southern blot analysis of
      respiratory and biliary cultures confirmed that the isolates were identical.
      Despite aggressive antibiotic therapy and drainage, persistent cholangitis and
      infection have not been eradicated after 6 months. The most likely mechanism of
      infection of the biliary tract was direct introduction of the upper respiratory
      tract pathogen during the diagnostic procedure.

PMID- 15463816
TI  - Cell and cytokine profile in nasal secretions in cystic fibrosis.
AB  - BACKGROUND: Nasal polyposis (NP) frequently complicates the course of cystic
      fibrosis (CF). The aim of this study was to determine the pattern of inflammatory
      cells and mediators in nasal secretions from patients with or without NP compared
      to patients with idiopathic NP and healthy controls. METHODS: Eighteen CF
      patients with NP (NP+ group: 6 untreated, 12 treated with nasal steroids), and 15
      without NP (NP- group) were included in this prospective study and compared to 9
      patients with idiopathic NP and 12 healthy controls. Differential cell count
      eosinophil cationic protein (ECP), interleukin-5 (IL-5) and IL-8 were determined
      in nasal lavage fluids. RESULTS: The total cell count, the number and the
      percentage of neutrophils and eosinophils, the levels of IL-8, IL-5 and ECP were
      significantly higher in nasal secretions from both NP+ and NP- as compared with
      controls. No difference was found between untreated and treated CF patients with
      NP. No difference was found between NP+ and NP- groups. Compared to idiopathic NP
      group, both NP+ and NP- groups had higher percentage of neutrophils and lower
      percentage of eosinophils. There were no differences according to the use of
      topical steroids, systemic antibiotherapy, or the type of mutation. CF patients
      with positive nasal culture had a higher percentage of neutrophils than those
      with negative culture. CF patients with atopy had a higher percentage of
      eosinophils than non-atopic patients. CONCLUSION: Our results demonstrate that
      nasal inflammation is a prominent feature in patients with CF and does not differ
      according to the presence of NP. IL-8 and IL-5 may play crucial roles in
      recruitment and activation of neutrophils and eosinophils in upper airways of CF
      patients.

PMID- 15463817
TI  - Peripheral muscle strength in young males with cystic fibrosis.
AB  - BACKGROUND: In children with cystic fibrosis there is a decrease in peak work
      capacity and oxygen consumption on maximal exercise testing when compared to
      controls. Previous studies have shown that peripheral muscle force is decreased
      in children with cystic fibrosis even in those with minimal changes in lung
      function. However, no studies have examined peripheral muscle strength using
      isokinetic dynamometry which permits measurement of muscle strength throughout
      range and is considered the gold standard in orthopaedics and sports medicine.
      METHODS: Isokinetic muscle strength was measured in the knee flexors and
      extensors and shoulder flexors and extensors at two speeds of movement in
      children with cystic fibrosis and matched controls. Activity levels in both
      groups were calculated. RESULTS: Thirteen subjects and 13 age and height matched
      controls were assessed. Average peak torque was calculated and expressed in terms
      of body weight. There was a significant difference in peak torque/body weight in
      children with cystic fibrosis when compared to controls. FEV1 was significantly
      correlated with knee muscle strength and shoulder flexion at 90 degrees /s in
      subjects with CF. CONCLUSION: Children with CF had lower muscle strength than
      control subjects. Airflow limitation was associated with decreased muscle
      strength. The relationship between muscle strength and exercise tolerance
      requires investigation.

PMID- 15463818
TI  - Parental fears of Pseudomonas infection and measures to prevent its acquisition.
AB  - BACKGROUND AND AIM OF THE STUDY: Chronic infection with Pseudomonas aeruginosa
      (PA) is associated with accelerated worsening of lung disease in patients with
      cystic fibrosis (CF). Fears of PA are widespread among parents of CF children,
      and many parents take precautions at home to prevent acquisition of the bacterium
      from the environment. The present study was undertaken to describe the type and
      intensity of these activities. METHODS: Parents of 21 CF children (7 without
      prior PA infection, 10 with intermittent and 4 with chronic PA infection) were
      investigated using semistructured interviews. These were analyzed descriptively
      and with respect to predominant themes. Additionally, a German personality test
      was used to evaluate the influence of psychological factors. RESULTS: The
      clinical impression of widespread parental anxieties of PA infection was
      confirmed. Misunderstandings concerning PA infections were related to a
      simplistic concept of the underlying biological mechanisms. Some parents which we
      classified as 'bacterium-focussed' thought that each contact with PA would lead
      to bacterial infection. These parents used a large variety of measures, which
      concerned both domiciliary and outdoor surroundings and activities. At the other
      end of the spectrum were parents which we classified as 'child-focussed' who
      mostly supported (and relied on) the child's defense mechanism instead of
      hygienic measures. CONCLUSIONS: Recommendations by physicians on how to prevent
      PA acquisition from the environment should take into account possible non
      intended side effects, since some parents will exaggerate daily precautions to
      the detriment of the child's (and the parent's) quality of life.

PMID- 15463819
TI  - Resting energy expenditure and lung disease in cystic fibrosis.
AB  - Optimal nutritional support is considered to be an integral part in the
      management of cystic fibrosis (CF). Several factors contribute to increased
      resting energy expenditure (REE), which itself can lead to energy imbalance and
      thus contribute to deterioration of the nutritional status. We aimed to assess
      the impact of lung parenchyma damage on REE and correlated these findings with
      forced expiratory volume in 1 s (FEV(1)). Twenty patients performed respiratory
      function testing (FEV(1)), pulmonary high-resolution computed tomography (HRCT)
      and assessment of REE with open circuit indirect calorimetry. HRCT was scored by
      using a modified Bhalla method. Mean HRCT score was 8.4 and mean REE value was
      108.4% predicted vs. 96.5% predicted of 16 healthy subjects (P<0.01). There was a
      significant correlation between HRCT score and REE (P<0.01), HRCT score and
      FEV(1) (P<0.001) and REE and FEV(1) (P<0.05). The correlations demonstrate a
      close correlation between lung damage and elevated REE in people with CF.
      Prevention of negative energy balance is an important part in follow-up of
      patients with CF. Any increase in REE should raise suspicion of progress in lung
      impairment.

PMID- 15463820
TI  - Validation of the SF-36 for the assessment of quality of life in adolescents and
      adults with cystic fibrosis.
AB  - BACKGROUND: Generic health-related quality of life measures are often applied to
      disease groups without assessment of their psychometric properties. The current
      work assesses the properties of the Short Form 36-item (SF-36) questionnaire in a
      British sample of adolescents and adults with cystic fibrosis (CF). METHODS: Two
      hundred and twenty-three adolescents and adults with CF completed the SF-36 with
      a further 185 approached and not responding by non-completion of the
      questionnaire. The structure and internal reliability of the instrument was
      assessed by principal components analysis, Cronbach alpha coefficients and item
      to domain correlations. Differences between disease severity groups were assessed
      by analysis of variance. RESULTS: Factor analysis of the SF-36 scores broadly
      confirmed domain structures for the SF-36. Cronbach alpha coefficients were high
      (range 0.82-0.91) and item-to-same domain correlations were stronger than item-to
      unrelated domain correlations. Examination of differences between mild, moderate
      and severe disease states revealed four significant main effects for: physical
      functioning, role limitation due to physical functioning, general health
      perceptions and energy and vitality. The analysis also revealed the presence of
      numerous ceiling effects across domains. CONCLUSIONS: The domain structure of the
      SF-36 was demonstrated to be robust. However, the discriminatory ability of the
      measure was disappointing. The presence of ceiling effects and the low frequency
      of differences between intermediate disease severity groups indicated that the SF
      36 was not discriminatory with respect to mild disease states or progression of
      illness.

PMID- 15463821
TI  - Falsely elevated serum tobramycin levels in a patient receiving nebulised
      tobramycin.
AB  - It is common when treating patients with respiratory exacerbations of cystic
      fibrosis to use both nebulised and intravenous antibiotics. Aminoglycoside drug
      levels are often measured from finger-prick blood samples. We describe a case of
      a 14-year-old girl treated simultaneously with IV and nebulised tobramycin in
      whom drug levels, measured from finger prick blood samples, were erroneously high
      due to finger contamination by the nebulised drug. Special precautions or direct
      venepuncture is essential when assessing antibiotic levels in such patients.

PMID- 15463822
TI  - Understanding bacterial biofilms in patients with cystic fibrosis: current and
      innovative approaches to potential therapies.
AB  - Chronic P. aeruginosa infection is characterized by production of mucoid alginate
      and formation of microcolonies (biofilm) as seen in the lungs of cystic fibrosis
      patients. Oxygen radicals produced by the inflammatory response polymorphonuclear
      leucocytes induces the alginate production. The biofilm mode of growth is the
      survival strategy of environmental bacteria and alginate biofilms are also
      protected against antibiotics and against the immune response in the lungs of the
      patient. Quorum sensing is important for early and mature biofilm formation and
      also for the severity of the infection. The new knowledge of the mechanisms
      involved in biofilm formation opens up new possibilities for therapeutic
      intervention strategies involving e.g. inhibitors of quorum sensing.

PMID- 15463823
TI  - Nebulised dornase alpha: adherence in adults with cystic fibrosis.
AB  - BACKGROUND: Dornase alpha improves sputum clearance and pulmonary function in
      patients with moderate bronchiectasis and cystic fibrosis (CF). Several studies
      have demonstrated variable adherence to treatment regimens in patients with CF.
      We aimed to compare self-reported adherence with computer based dispensing
      records of dornase alpha. METHOD: Direct interview of adherence to dornase alpha
      was compared with pharmacy-dispensing records during a 12-month period. The
      reasons for dornase alpha usage, and change in lung function in three groups of
      patients were compared (group 1 (n=42): positive trial, continuing therapy; group
      2 (n=13): positive trial, ceased therapy; group 3 (n=22): negative trial). Ninety
      patients with CF were surveyed. Patients who had ceased dornase alpha provided
      reasons for drug cessation. Lung function and anthropometric data were collected
      prior to dornase alpha treatment and at 3 years. Health care professionals rated
      adherence to therapy. RESULTS: Of the 42 patients on dornase alpha, the average
      utilisation was 197 days (54%). From dispensing records, 24% of patients were
      classified as good adherence, 46% as moderate adherence and 30% as poor
      adherence. Eighty-two percent claimed to use dornase alpha therapy more than 20
      days/month, whereas dispensing records showed that only 24% of collected
      sufficient drug supplies. Health professionals' assessment of adherence of
      therapy was often incorrect and an overestimation was more common than
      underestimation. The change in FEV(1) 3 years after trial was not significantly
      different between groups. There was a negative correlation between initial
      response to dornase alpha and baseline FEV(1) (r=-0.44, P=0.001), however,
      initial response was not related to the change in FEV(1) over 3 years (r=0.20,
      P=0.16). CONCLUSION: There is variability in adherence to dornase alpha in adults
      with CF and patient self-reporting is likely to over-estimate drug collection
      from the pharmacy. Further study of the long-term effects of dornase alpha is
      required. To date, proven interventions to enhance adherence are limited and
      require investigation in CF.

PMID- 15463824
TI  - Fecal elastase-1 cut-off levels in the assessment of exocrine pancreatic function
      in cystic fibrosis.
AB  - BACKGROUND: Fecal elastase-1 (E1) test is a sensitive and specific indirect test.
      However, there are few data on the best cut-off level in the assessment of
      exocrine pancreatic function in cystic fibrosis (CF). MATERIAL AND METHODS: In
      725 CF patients and 243 healthy subjects (HS) from Greece, Russia, Poland and the
      United Kingdom, E1 concentrations were measured. The best cut-off levels for the
      discrimination between CF and HS (for whole group as well as for individual
      countries) were calculated. RESULTS: The best cut-off level for the
      differentiation between CF pancreatic insufficiency and normal pancreatic
      function in HS was found to be 184 microg/g of feces. However, some inter-country
      differences were stated. E1 concentrations in the UK subgroup were significantly
      lower than those found in Polish and Russian CF patients. E1 concentrations in
      Greek patients were significantly higher than in the other countries. However, E1
      concentrations in Delta F508 homozygotes were very similar in all studied
      subgroups. IN CONCLUSION: In clinical practice, instead of a single best cut-off
      level for the E1 test, we suggest using a range of values (160-200 microg/g). The
      presence of different best cut-off levels within countries is a practical
      consequence of the different distribution of pancreatic function.

PMID- 15463825
TI  - Variability of fecal pancreatic elastase measurements in cystic fibrosis
      patients.
AB  - BACKGROUND: the fecal pancreatic elastase-1 (EL-1) test is a new non-invasive
      test for pancreatic function. The aim of the study was to evaluate the intra
      patient variability of the fecal EL-1 test in a cystic fibrosis (CF) population.
      METHODS: 26 CF patients were recruited. Mean patient (S.D.) age was 13.7 years
      (5.39). Nineteen patients had classical pancreatic insufficiency (PI) based on a
      clinical syndrome of malabsorption plus steatorrhea on a 72 h fecal fat balance.
      They were all treated with enzyme supplements. Four patients had classical
      pancreatic sufficiency (PS): no symptoms of malabsorption, no steatorrhea on a 72
      h fecal fat balance, no enzyme treatment. Two patients had symptoms suggestive of
      PI but had a normal 72 h fecal fat balance: (doubtful pancreatic status (PD)).
      The CF patients were asked to collect stool samples on 7 consecutive days. EL-1
      content in the samples was measured in duplicate. A cut-off of 200 microgEL-1/g
      stool was used for diagnosing PI. RESULTS: mean intra-assay variability was
      4.06%. All PI patients had EL-1 levels below detection limit. For the PS group
      maximal intra-patient variability was 35%, one stool sample EL-1 level was below
      the 200-microg cut-off. In the PD group the maximal intra-patient variability was
      37% and EL-1 levels were inconclusive for the diagnosis of PI in both patients.
      CONCLUSIONS: the EL-1 test can be used for diagnosing severe PI in CF patients
      with overt clinical symptoms of malabsorption. However, in CF patients where the
      clinical picture is less clear the EL-1 test may be inconclusive due to
      significant intra-patient variability.

PMID- 15463826
TI  - Cytokine concentrations and neutrophil elastase activity in bronchoalveolar
      lavage and induced sputum from patients with cystic fibrosis, mild asthma and
      healthy volunteers.
AB  - BACKGROUND: Induced sputum (IS) has been proposed as a non-invasive alternative
      to bronchoalveolar lavage (BAL) for the assessment and monitoring of airways
      inflammation. The aim of this study was to compare both methods in patients with
      cystic fibrosis (CF). The possible differences between subjects with CF, mild
      asthma and healthy volunteers (HV) was also assessed. METHOD: In a single centre,
      randomised, two way crossover study, 11 patients with CF, 9 mild asthmatics (MA)
      and 11 HV underwent BAL and hypertonic saline induction on consecutive days. Free
      neutrophil elastase (NE), neutrophil elastase/alpha(1)-anti-trypsin complex (NE
      AAT), tumour necrosis factor receptor (p55) and interleukin-8 (IL-8) were
      measured in cell free supernatants. RESULTS: Three CF patients reported serious
      adverse events following BAL. NE was usually undetectable in both IS or BAL
      samples and NE-AAT concentrations did not differ consistently between the two
      sampling methods. IL-8 and p55 levels in the CF patients tended to be higher in
      IS samples compared with BAL samples (median 19,860 vs. 3,855 pg/ml and 2.55 vs.
      0.29 ng/ml, respectively). There was a significant difference in mean p55
      concentrations between CF, MA and HV in IS samples (P=0.003) but not in BAL
      samples (P=0.36). The difference in mean IL-8 concentrations in IS samples
      between subject groups was statistically different (P=0.023). CONCLUSIONS: IS
      samples can be safely obtained from CF patients. Analysis of IS samples can help
      to characterize the inflammatory process in the airways of CF patients. The
      serious adverse events following BAL in 3 CF patients highlight an inherent risk
      associated with this procedure.

PMID- 15463827
TI  - Assessment of nutritional status in children with cystic fibrosis: conventional
      anthropometry and bioelectrical impedance analysis. A cross-sectional study in
      Dutch patients.
AB  - BACKGROUND: Assessment of nutritional status in children with cystic fibrosis
      (CF) is clinically relevant. Methods to measure nutritional status should be
      reliable and non-invasive, and reference values should be available. AIM: To
      compare weight and height measurements and measurements of specific body
      compartments in children with CF. METHODS: In a cross-sectional survey of 58
      children with CF (28 females), we compared height and weight (expressed as:
      weight-for-height, body mass index (BMI), height-for-age and weight-for-age) with
      fat mass (skinfold sum (SFS)), muscle mass (upper arm circumference (UAC)) and
      bioelectrical impedance analysis (BIA). Results were expressed as Z-scores, using
      Dutch reference values. RESULTS: BMI and weight-for-height were within the normal
      range (mean Z-score (range): -0.13 (-1.5, 2.7) and -0.02 (-1.7, 2.8)). Weight and
      height corrected for age were below normal (mean Z-score (range): -0.79 (-2.4, 
      0.05) and -1.2 (-2.8, 1.4) (P<0.01)). Lean body mass by skinfold sum (LBM(sfs)),
      UAC and BIA were also significantly below reference values (mean Z-score (range):
      -0.9 (-2.2, 1.8), -0.95 (-2.4, 1.8) and -1.1 (-3.6, 1.0) (P<0.01)). Lean body
      mass (LBM) by BIA correlated with LBM(sfs). BIA systematically underestimated LBM
      in both CF patients and in control subjects. CONCLUSION: Nutritional status of
      children with CF must be evaluated, using age-corrected weight and height
      expressed in Z-score. LBM estimated by SFS, UAC and by BIA appear to be useful,
      although longitudinal studies in CF children should be performed to evaluate
      their clinical significance in detecting changes in nutritional status.

PMID- 15463828
TI  - Predictors of desaturation during formal hypoxic challenge in adult patients with
      cystic fibrosis.
AB  - Assessment of the potential risk of in flight hypoxaemia in patients with cystic
      fibrosis is often based on a hypoxic challenge where individuals have saturations
      and/or blood gases taken before and after inspiring 15% normobaric oxygen. The
      aim of this study was to see if routine clinical measurements could predict the
      outcome of this test. This was a prospective study comparing the modified 6-min
      walking test, lung function, body mass index, Northern (N) and Shwachman
      Kulczycki (SK) scores with a hypoxic challenge (flight test) in 69 adults
      attending the Leeds regional CF Unit. Although, there was a significant
      correlation between post flight test PaO(2) and N score (P=0.003), SK score
      (P=0.002), FVC % predicted (P=0.01), FEV(1) % predicted (P=0.002), resting
      saturations (P<0.001), 6 min saturation on walking test (P<0.001) and baseline
      PaO(2) (P<0.001), no single parameter could accurately predict all patients who
      desaturated during the flight test. No individual clinical parameter appears to
      fully predict the need for in flight oxygen but patients most at risk appear to
      have either a low FEV(1) (<60%), high N score (>13) or low baseline PaO(2) (<10.5
      kPa).

PMID- 15463829
TI  - Creon 10,000 Minimicrospheres vs. Creon 8,000 microspheres--an open randomised
      crossover preference study.
AB  - Creon 10,000 Minimicrospherestrade mark (Creon) 10,000 MMS) is a pancreatic
      enzyme formulation that contains smaller spheres of pancreatin in a 50% smaller
      capsule than conventional microspheres (Creon) 8,000). This three-centre study
      investigated the preference of cystic fibrosis (CF) patients for these products.
      In one centre, 72 h stool fat excretion and coefficient of fat absorption (CFA)
      were also compared. Fifty-nine patients with a mean age 10 years (range 3-17)
      took Creon 8,000 ms for 14 days and were then randomised to 28 days of Creon
      8,000 ms followed by 28 days of Creon 10,000 MMS, or vice versa. Dosing was
      lipase for lipase according to the labelled declaration. At the end of the second
      treatment period, 51 of 54 patients who completed the study expressed a
      preference, with a statistically significant preference in favour of Creon 10,000
      MMS (47/51; 87%) vs. Creon 8,000 ms (4/51; 7.4%; P<0.0001). Stool fat (g/day) and
      CFA (%) were measured in 24 patients at the end of each treatment period: the
      products were therapeutically equivalent (Creon 10,000: 8.4 g/day, 91.3% CFA;
      Creon 8,000: 6.7 g/day, 93.5% CFA). Both products were well tolerated. In
      conclusion, in CF children we found a clear preference for Creon 10,000 MMS
      compared with Creon 8,000 ms with no difference in fat absorption between the two
      products. Creon 10,000s smaller capsules are easier to take and should aid
      patient compliance.

PMID- 15463830
TI  - Burkholderia cepacia genomovar III and Burkholderia vietnamiensis double
      infection in a cystic fibrosis child.
AB  - Herein we report a case of a cystic fibrosis child who was simultaneously
      infected with Burkholderia cepacia genomovar III and Burkholderia vietnamiensis.
      After antimicrobial therapy only B. cepacia genomovar III persisted.

PMID- 15463831
TI  - Comment on "Effects of pregnancy on health: certain aspects of importance for
      women with cystic fibrosis.".

PMID- 15463832
TI  - Abstracts of the 25th European Cystic Fibrosis Conference. Genoa, Italy, June 20
      23, 2002.

PMID- 15463833
TI  - Inhaled antibiotic therapy: What drug? What dose? What regimen? What formulation?
AB  - Early studies of the use of antibiotics in patients with cystic fibrosis
      suggested that they would be of benefit in preventing or reducing infection by
      Pseudomonas aeruginosa. In seeking to optimize treatment, factors such as the
      drug used, the dose, the regimen and the formulation must be considered.
      Aminoglycosides are ideal for aerosolization because they have a long post
      antibiotic effect and have an acceptable taste. Tobramycin is one of the
      aminoglycosides with the lowest systemic toxicity, which enables the aerosol
      delivery of doses high enough to overcome the antagonistic effects of the sputum.
      The most dramatic benefits from inhaled tobramycin have been shown to occur in
      the first 2-4 weeks of administration. Continual administration for longer
      periods can result in the development of resistance and loss of the improvement
      in lung function. However, this resistance is transient, and susceptibility to
      tobramycin returns after a short drug holiday. Optimal drug administration
      therefore consists of a 4-week on, 4-week off cycle. Such a cycle also helps to
      maintain patient compliance. Successful drug delivery also depends upon a
      formulation that does not provoke bronchoconstriction, which demands a
      formulation that is both preservative free, and osmotically and pH balanced. This
      research has enabled the development of a novel formulation of tobramycin
      optimized for use as an inhalation therapy in cystic fibrosis.

PMID- 15463834
TI  - The long-term use of inhaled tobramycin in patients with cystic fibrosis.
AB  - Tobramycin nebuliser solution (TNS) has been investigated in several clinical
      trials, including a large, placebo-controlled study that demonstrated efficacy
      over a 24-week period. The open-label extension phase of this trial enabled
      observations to be conducted for an additional period of almost 18 months.
      Patients from both treatment arms (n=396) entered the open-label phase and
      received up to nine 28-day on, 28-day off cycles of TNS 300 mg by aerosol twice
      daily (b.i.d.). Mean lung function in patients who had received placebo during
      the double-blind phase improved during the first three cycles of the open-label
      treatment. However, lung function in these patients did not recover to the levels
      seen in those patients who had received TNS throughout the double-blind and open
      label phases. In both groups of patients, improvement was maintained during the
      study. Greater improvements were seen in adolescents compared with older
      patients. Adverse events were generally uncommon, with a notably lower incidence
      of fever, anorexia, abdominal pain and vomiting than was observed in the double
      blind phase among patients who received placebo, and a generally low incidence of
      tinnitus. We conclude that long-term TNS administration is safe and effective.

PMID- 15463835
TI  - New clinical evidence from the European tobramycin trial in cystic fibrosis.
AB  - The major cause of morbidity and mortality in patients with cystic fibrosis (CF)
      is respiratory disease (Penketh et al., Thorax 1987; 42: 526-532). Recent studies
      in the USA have shown that intermittent administration of inhaled tobramycin is
      beneficial to patients with CF who are chronically infected with Pseudomonas
      aeruginosa (Ramsey et al., N Engl J Med 1999; 340: 23-30; Ramsey et al.,
      Proceedings of the 12th Annual North American Cystic Fibrosis Conference, 1998,
      Montreal, Canada; Ramsey et al., Abstract from 23rd European Cystic Fibrosis
      Conference, 1999, the Hague, Netherlands). In Europe, the use of nebulised
      colistin in patients chronically infected with P. aeruginosa is widespread. A
      recently published study compared the efficacy and safety of tobramycin nebuliser
      solution (TNS) and nebulised colistin in CF patients . One hundred and fifteen
      patients were randomised to receive either TNS or colistin in a multi-centre open
      labelled study that assessed change from baseline in FEV(1) and sputum P.
      aeruginosa density. TNS produced a mean 6.7% improvement in lung function
      (P=0.006), whilst there was no significant improvement in the colistin-treated
      patients. The TNS-treated patients had a significantly greater improvement in
      lung function than those treated with colistin (P=0.008). The safety profile of
      both treatments was good. We conclude that patients treated with TNS for 1 month
      experience improved lung function compared with patients treated with colistin.

PMID- 15463836
TI  - Insights into cystic fibrosis microbiology from the European tobramycin trial in
      cystic fibrosis.
AB  - The infection of the airways of cystic fibrosis patients by Pseudomonas
      aeruginosa is a complex, multistaged process that is associated with a
      deterioration of lung function. The complexity of the formation of biofilms and
      their interaction with the immune system means that treatment with antibiotics
      has been an uncertain science. Tobramycin nebuliser solution (TNS) is a novel
      formulation of the antibiotic tobramycin developed specifically for inhalation. A
      recent large trial comparing TNS with inhaled colistin provided an opportunity to
      define further the effect of antibiotic treatment on microbial infection. In the
      TNS group, the percentage of patients with a tobramycin minimal inhibitory
      concentration (MIC) > or = 4 mg l(-1) increased from 38 to 49%, and the
      percentage of patients with a colistin MIC > or = 4 mg l(-1) remained at 55%. In
      the colistin group, the percentage of patients with a colistin MIC > or = 4 mg l(
      1) remained at 34%, whereas the percentage of patients with a tobramycin MIC > or
      = 4 mg l(-1) decreased from 27 to 16%. Furthermore, clinical and bacterial
      response to TNS and colistin was independent of the MIC at baseline. Neither
      antimicrobial therapy was associated with infection by Burkholderia cepacia or
      other inherently resistant pathogens. We conclude that conventional measures of
      antimicrobial resistance may underestimate the effectiveness of tobramycin and
      colistin when delivered at the high concentrations achieved with the TNS
      formulation.

PMID- 15463837
TI  - Inhaled antibiotic therapy in evidence: what delivery device?
AB  - This paper evaluates the suitability of various compressors available in Europe
      to generate and deliver tobramycin nebulizer solution to cystic fibrosis patients
      from the PARI LC PLUS jet nebulizer. This evaluation has been undertaken (i) by
      establishing an in vitro equivalence to the DeVilbiss PulmoAide compressor
      (operating at 4.6 l/min) proven effective in US clinical trials, and (ii) by
      determining equivalent in vitro performance of the LC PLUS nebulizer driven by
      alternative airflows. Equivalent performance is judged as having both an aerosol
      output and aerosol size within +/-10% of that obtained with the LC PLUS/PulmoAide
      combination. The two different in vitro methodologies applied to this
      investigation were based on the British Standard and a European Standard to
      assess nebulizer output. The results demonstrate that a wide range of compressed
      airflow rates generate aerosol output from the PARI LC PLUS equivalent to that
      obtained from the PulmoAide compressor. This range of airflows encompasses many
      compressors commonly available in Europe.

PMID- 15463838
TI  - Sweat conductivity and chloride titration for cystic fibrosis diagnosis in 3834
      subjects.
AB  - Sweat test is the standard for cystic fibrosis (CF) diagnosis. Conductivity is an
      alternative method not yet approved, in spite of its good correlation with
      chloride concentration. The aim was to assess the capacity of sweat conductivity
      to discriminate between CF and non-CF subjects. Automated measurements of
      conductivity and chloride concentration were carried out on the same sweat
      samples from subjects with clinical suspicion of CF. Sweat samples from 3,834
      subjects, median age 1.8 years (range 1 month-54 years) were analysed, and those
      with chloride titration >60 mmol/l were considered as CF patients (n=294).
      Conductivity median values in CF and non-CF subjects were 111 mmol/l (82-148) and
      36 mmol/l (12-89), respectively. The Spearman correlation between chloride
      titration and conductivity was r=0.60 (P<0.001). The receiver operating
      characteristics (ROC) curve showed very high agreement between two methods. The
      best conductivity cut-off value to diagnose CF was > or =90 mmol/l (sensitivity
      99.7%, specificity 100%, positive and negative predictive values of 100% and
      99.97%, respectively, and kappa=0.998). Likewise, the best conductivity cut-off
      value to exclude CF was <75 mmol/l. The sweat conductivity method showed good
      correlation with chloride titration, and accurately discriminated between
      subjects with and without CF. In accordance with this, CF diagnosis might be
      confirmed for conductivity values > or =90 mmol/l and excluded for <75 mmol/l.
      Values between 75 and 89 mmol/l should correspond to an equivocal range. However,
      more studies are needed to confirm the role of conductivity in definitive CF
      diagnosis.

PMID- 15463839
TI  - The 12-min walk test as an assessment criterion for lung transplantation in
      subjects with cystic fibrosis.
AB  - Timing for the evaluation and listing of patients with cystic fibrosis who are
      candidates for lung transplantation is still uncertain. Our study goal was to
      determine the value of the 12-min walk test as a simple and easy-to-use
      adjunctive assessment tool for pre-transplant evaluation. A total of 34 cystic
      fibrosis patients (17 male, mean age 22 years) with end-stage lung disease were
      evaluated in this retrospective analysis. The 12-min walk test was carried out
      according to an established protocol. Before walking, body plethysmography was
      performed and a capillary sample was taken for blood gas analysis. Walking
      distance and SaO(2) via continuous pulse oximetry were recorded online. There was
      a strong correlation between survival time and walking distance (r=0.7, P=0.003).
      No other single parameter, such as FEV(1), SaO(2,) pCO(2) or BMI, showed a
      statistically significant correlation with survival time. Subjects who walked <
      or =700 m had a lower cumulative survival (P=0.02). There was a statistically
      significant positive correlation between walking distance and SaO(2) at rest and
      after 12 min of walking (r=0.5, P=0.001; and r=0.5, P=0.04, respectively). There
      was no correlation between walking distance and pCO(2) at rest, BMI, FEV(1), or
      degree of change in SaO(2) during the walk test. This study demonstrates that in
      CF patients with end-stage lung disease, walking distance during a 12-min walk
      test is more informative with respect to survival than single parameters such as
      SaO(2,) pCO(2), FEV(1) or BMI.

PMID- 15463840
TI  - CFTR gene mutations in Japanese individuals with congenital bilateral absence of
      the vas deferens.
AB  - Congenital bilateral absence of the vas deferens (CBAVD) is a monosymptomatic
      disease confined to the male reproductive system with similarity to the phenotype
      of cystic fibrosis (CF), and mutations in the CFTR gene are highly prevalent in
      Caucasian CBAVD patients. While CF is very rare in Japan, CBAVD is not. Our
      previous study demonstrated high prevalence of the 5T allele in the CFTR gene in
      Japanese CBAVD patients. We analyzed whole exons of the CFTR gene in 19 CBAVD
      patients and 53 normal individuals using polymerase chain reaction amplification
      single strand conformation polymorphism analysis and direct sequencing. Three
      missense mutations (W216X, G1349S, Q1352H) were found in seven CFTR alleles, and
      the 5T allele was positive in 11 of 38 CFTR patient alleles. Consequently, 47% of
      CFTR chromosomes in the patients were affected, and 11 individuals (58%) had at
      least one mutated CFTR allele. In contrast, three of 53 normal individuals (5.7%)
      had a missense mutation in one of the CFTR genes, but no 5T allele was detected
      (both P<0.0001). Mutations of the CFTR gene are closely associated with Japanese
      patients with CBAVD.

PMID- 15463841
TI  - Fosfomycin therapy for multiresistant Pseudomonas aeruginosa in cystic fibrosis.
AB  - BACKGROUND: Increasing resistance to standard antibiotics has been demonstrated
      in CF patients colonised by Pseudomonas aeruginosa. The antibiotic Fosfomycin has
      a unique mode of action against this organism, and may protect against
      aminoglycoside mediated renal and ototoxic effects. However, there is little
      published experience of this drug in IV form, and it is not licensed for use in
      the UK. METHODS: In combination with other antibiotics, we used Fosfomycin to
      treat 30 pulmonary exacerbations in 15 adult CF patients colonised by P.
      aeruginosa, mainly multiresistant strains. All patients gave informed consent. We
      cultured sputum prior to treatment and measured spirometry, renal function, and
      symptoms before and after treatment, and recorded any side effects. RESULTS: One
      patient developed nausea and Fosfomycin treatment was withdrawn. The remaining
      patients showed clinical resolution of their chest exacerbations (mean FEV1%
      predicted: pre 41.1 vs. post 49.4, P<0.001). Although there was a statistical
      increase in plasma urea (pre 3.9 mmol/l vs. post 4.3, P<0.03), this was still
      within the normal range. Plasma creatinine was unchanged. CONCLUSIONS: This study
      shows that IV Fosfomycin is well tolerated by adult patients with CF and can be
      useful in the treatment of those colonised with multiresistant P. aeruginosa.

PMID- 15463842
TI  - A pilot study of zafirlukast as an anti-inflammatory agent in the treatment of
      adults with cystic fibrosis.
AB  - BACKGROUND: Persistent endobronchial inflammation is in part responsible for the
      attrition of lung function seen in cystic fibrosis. Leukotrienes act as pro
      inflammatory mediators. The aim of this study was to assess the efficacy of the
      leukotriene receptor antagonist zafirlukast as a potential anti-inflammatory
      agent in the treatment of adult patients with cystic fibrosis. METHODS:
      Clinically stable patients were enrolled in the study if they had no history or
      clinical evidence of asthma, bronchial hyper-reactivity, or aspergillosis. They
      were randomised to receive zafirlukast 20 mg twice daily with all routine
      treatment for four months or routine treatment alone in an open cross-over
      design. Primary endpoints were changes in respiratory function tests and a
      modified NIH clinical score. RESULTS: Thirty patients were enrolled and 25
      completed. There was a significant improvement in the modified NIH clinical score
      but no significant increase in respiratory function with zafirlukast.
      CONCLUSIONS: Patients receiving a leukotriene receptor antagonist in addition to
      routine treatments showed significant improvement in a clinical score which is a
      composite of clinical wellbeing, chest radiograph appearance, and physical
      examination. Respiratory function showed a non-significant trend towards
      improvement with treatment. Zafirlukast may benefit patients with CF. An
      adequately powered study is justified on the basis of these results.

PMID- 15463843
TI  - Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in
      cystic fibrosis patients.
AB  - BACKGROUND: Patients were defined each successive month as either 'chronic' when
      more than 50% of the preceding 12 months were PA culture positive, 'intermittent'
      when < or =50% of the preceding 12 months were PA culture positive, 'free of PA',
      with no growth of PA for the previous 12 months, having previously been PA
      culture positive, or 'never infected', when PA had never been cultured. METHODS:
      Cross-sectional analysis of 146 children attending the Leeds Regional Cystic
      Fibrosis Centre was performed to assess relationship between the new definition
      and clinical scores and investigations. The response variable was regressed on
      age and sex and the residuals analysed using the Kruskal-Wallis test. RESULTS:
      The 'chronic' group (18% of patients) had significantly worse Shwachman-Kulczycki
      (SK) and Northern chest X-ray scores, and % predicted FEV(1) values than the
      'free' (28%) or 'never' (20%) categories (P<0.004). The 'intermittent' group
      (34%) had a significantly higher SK score than the 'chronic' group (P<0.0001),
      and a significantly lower % predicted FEV(1) value than the 'free' or 'never'
      groups (P<0.0003). 'Chronic' patients were significantly associated with a
      positive, and 'never' patients with a negative, PA antibody result (P<0.001).
      CONCLUSIONS: The validity and importance of identifying these four subgroups is
      demonstrated. Previous definitions may over-estimate the prevalence of chronic
      infection.

PMID- 15463844
TI  - Granulomatous diseases in a patient with cystic fibrosis.
AB  - We report the case of an adult with Crohn's disease and pulmonary sarcoidosis on
      the background of cystic fibrosis (CF). There is a recognized association between
      Crohn's colitis and CF, but cases of pulmonary sarcoidosis in CF are rare. There
      may be a pathogenic link between the two granulomatous disorders and CF with
      chronic immune stimulation leading to hyperimmunoglobulinemia, circulating immune
      complexes and subsequent granuloma formation.

PMID- 15463845
TI  - Cultural issues in cystic fibrosis.
AB  - Although current numbers of non-Caucasian CF patients are small, collectively
      they represent sizeable groups and increasingly more is becoming known about the
      spectrum of mutations in the CFTR gene in different populations. As such it is
      important to acknowledge that there will be certain sociocultural challenges in
      interacting with and managing such patients. This paper explores such
      developments and considers some of the current and future challenges facing those
      who treat the disease. Techniques applied in other illness contexts for
      establishing and maintaining effective patient-professional relationships,
      reviewing patient education, resolving treatment conflicts and improving
      adherence are discussed, as are the implications for future research.

PMID- 15463846
TI  - Patient-clinician conflict: causes and compromises.
AB  - Conflict is an everyday phenomenon, a part of everyday life. It is hardly
      surprising that it also occurs in a clinical setting, not only between clinicians
      and within teams, but also between patients, their families and clinicians. This
      is all the more the likely in a setting that deals with a chronic disease such as
      CF. The physical, emotional, social and practical burdens of the illness are such
      that coping mechanisms are stretched to their limits. Disagreements,
      misunderstandings, impaired trust and different expectations may all challenge
      the patient-clinician relationship. In a context in which children and
      adolescents form at least half the clientele, the potential for conflict is
      intensified because of the involvement of parents. This paper emphasises the
      normality of such conflicts, and using case illustrations, explains the reasons
      for conflicts and explores how best to resolve them. The basic principles of
      conflict-resolution are outlined, and useful techniques, readily applicable in
      everyday practice, are described.

PMID- 15463847
TI  - Survival against the odds.
AB  - While the majority of patients with cystic fibrosis (CF) survive well into
      adulthood, some do so against the odds. The severity of their illness, their
      psychosocial environment, or their failure to adhere to treatment are such that
      survival could not have been predicted. It appears that some patients are more
      resilient than others. Some specific components of resilience include
      comprehensibility, manageability and meaningfulness. These are defined and case
      examples provided to illustrate their significance.

PMID- 15463848
TI  - The psychosocial correlates of transplant survival.
AB  - BACKGROUND: due to the shortage of organs, half of the patients on the waiting
      list for transplantations die. Clinicians have a duty to identify those patients
      whom might benefit most. The correlation between psychosocial factors and
      survival in children who have received lung transplantation for CF has not been
      investigated. AIMS: to examine: (1) differences in physical, demographic and
      psychological factors between two groups of children with CF, those who did or
      did not survive the waiting period for transplantation. (2) Correlations between
      these factors pre-transplantation and length of survival post transplantation.
      METHODS: 81 children--mean age 11 years 6 months--and their parents underwent
      semi-structured standardised interviews and completed standardised instruments
      prior to being placed on the transplantation waiting list. The following domains
      were measured: child's disability, psychiatric status and self-esteem; quality of
      marital relationship and parental psychiatric status; and family attitudes and
      functioning. RESULTS: 20% of the children on the waiting list had a psychiatric
      disorder and 60% of the parents scored within the psychiatric disorder range. One
      third of the parents had marital difficulties, and 20% of the families showed
      chaotic functioning. Only half of the children survived to receive
      transplantation. Survivors and non-survivors were comparable with regard to all
      psychological measures. A follow up of the transplanted children, ranging from 3
      to 156 months post-transplantation, produced a group of nine survivors and 30 non
      survivors. Only two pre-transplant factors showed a significant association with
      length of survival after transplantation. Severe physical disability was
      associated with longer survival (P=0.01), and parental hostility to partner was
      associated with a shortened life span (P=0.04). No other factors were
      significantly associated with length of survival. CONCLUSION: there is no
      evidence to suggest that adverse psychosocial factors should be used as a
      contraindication to transplantation.

PMID- 15463849
TI  - Survival without transplant.
AB  - Patients with severe cystic fibrosis who face lung transplant proposal react in
      different ways to the offer of this potentially life prolonging therapy. Little
      is known about those patients who refused the operation. This article describes
      various behaviour patterns and reactions following the transplant proposal. The
      major reasons for refusal of lung transplantation are based on personal
      experiences and encounters and on psychological and medical considerations. Only
      a subgroup of patients sticks to the initial decision of refusing the operation.
      Other patients question their decision and fluctuate between refusal and
      acceptance. A third group of patients reverses the decision mostly as a result of
      a significant life event. The decision not to undergo lung transplantation needs
      to be viewed as a reversible one and in the context of extreme physical and
      psychological vulnerability on the part of the patients. Health professionals
      should recognise the potential for change, remain non-judgmental and flexible,
      and adjust their services to the respective circumstances.

PMID- 15463850
TI  - What can we learn from other illnesses?
AB  - I would like to begin by putting forward the idea that there is much to be gained
      from a more generic as opposed to a medical model in working with chronically
      sick children. I would like to consider the potential advantages of this generic
      approach, and then go on to consider more specifically what can be learned,
      firstly, from the specific example of childhood cancer and, secondly, from
      chronic illness more generally. Whether we work with children with cancer, cystic
      fibrosis or any other chronic condition, we have to be impressed by the child's
      capacity to 'survive against the odds'. While early work described the problems
      or deficits shown by sick children, it is now clear that there is huge
      variability in outcomes. Many children show extraordinary resilience and coping.
      We are increasingly concerned about quality of life (QOL) as well as quantity of
      survival. In expanding on the thesis that much can be learned from other
      diseases, I am going to use QOL as an example.

PMID- 15463851
TI  - The psychosocial and psychiatric side of cystic fibrosis in adolescents and
      adults.
AB  - Increasing numbers of cystic fibrosis (CF) patients are surviving into adulthood.
      An understanding of the psychiatric and psychosocial aspects of CF in adults and
      adolescents is therefore more important than ever. There is a large body of
      evidence indicating that the psychological and psychosocial functioning of people
      with CF is similar to that of well people, until the disease becomes severe.
      However, there is also evidence that patients do suffer an increased likelihood
      of psychiatric problems, such as depression, and of scoring poorly on physical
      functioning measures of quality of life. Studies have found conflicting evidence
      as to any association between degree of respiratory impairment and psychological
      functioning. Coping styles seem to have a large effect upon the quality of life
      of CF patients. People with cystic fibrosis can have problems with sexuality,
      platonic relationships and independence. Families of patients also suffer
      problems, which can affect the patients themselves. Non-compliance is a
      complicated problem with many patients. New treatments for people with CF are
      emerging, such as lobe transplants from live donors and gene therapy, with
      possible new psychosocial problems resulting. Furthermore, older studies are
      becoming increasingly inapplicable as treatment and prognosis changes. Therefore,
      more research is needed in this field.

PMID- 15463852
TI  - Improved lung function and body mass index associated with long-term use of
      Macrolide antibiotics.
AB  - BACKGROUND: A number of studies have suggested that the non-antimicrobial actions
      of macrolide antibiotics may be valuable in treating patients with cystic
      fibrosis. The use of long-term macrolide antibiotics for the management of CF
      patients colonised by Pseudomonas aeruginosa and progressive pulmonary disease
      was introduced into our clinic in 1997. A retrospective study was undertaken to
      assess of the impact of this therapy. METHODS: Twenty patients with progressive
      pulmonary disease (>10% fall in FEV(1) over 12 months despite optimising
      conventional therapy) were commenced on Azithromycin, 250 mg daily during a 21
      month period. At the time of assessment they had remained on therapy for a mean
      of 0.9 years. Changes in lung function, weight, body mass index (BMI) and
      frequency of pulmonary exacerbations were assessed. A group of 20 patients with
      stable lung function and matched as far as possible for age and sex was
      identified for comparison. RESULTS: Pulmonary function increased significantly in
      the Azithromycin group with FEV1% predicted increasing from a mean of 50.2-59.1%
      (P=0.001) while FVC% predicted increase from 64.5 to 76.1% (P=0.002). There was
      small but non-significant fall in lung function in the comparison group. Body
      mass index increased by a mean of 1.1 in the Azithromycin group but remained
      unchanged in the comparison group. The number of pulmonary exacerbations
      requiring intravenous antibiotics declined by 48.3% in macrolide treated subjects
      compared to the pre-treatment period (P<0.025); frequency of exacerbations in the
      control group was unchanged. CONCLUSION: Long-term Azithromycin treatment in
      patients with progressive deterioration in lung function appears to have led to
      an improvement in pulmonary function, increased body mass index and decreased the
      frequency of pulmonary exacerbations requiring intravenous antibiotics.

PMID- 15463853
TI  - Inhaled budesonide induced Cushing's syndrome in cystic fibrosis patients, due to
      drug inhibition of cytochrome P450.
AB  - Two CF patients developed Cushing's syndrome during administration of inhaled
      budesonide (400 microg/d) with oral itraconazole in one and with clarithromycin
      in the other patient. Clinical features appeared respectively after 2 and 6 weeks
      of drug co-administration, with prolonged adrenal suppression, and a slow
      recovery after ceasing the drugs. Inhibitors of the cytochrome P450 interfere
      with the metabolism of corticosteroids. Combination of these drugs even with
      moderate doses of budesonide should be closely monitored.

PMID- 15463854
TI  - Growth in prepubertal children with cystic fibrosis, homozygous for the Delta
      F508 mutation.
AB  - BACKGROUND AND METHODS: In cystic fibrosis, growth and lung function have been
      identified as prognostic markers of both severity of pulmonary disease and
      survival. Cross-sectional studies in patients with cystic fibrosis (CF) including
      all genotypes have shown that in prepubertal patients with lifetime continuous
      care within a specialised CF centre, growth can normalise. No corresponding
      improvement in lung function has been found. We used a longitudinal design to
      determine whether normalisation of growth could be found in the genetic subgroup
      of prepubertal children with CF with the homozygous Delta F508 mutation, which is
      one of the known severe mutations. METHODS: Data of all children born after 1980
      with the homozygous Delta F508 mutation, diagnosed in early childhood at the
      specialised centre of the Children's Hospital of Berne were systematically
      assessed up to the age of 11 years and retrospectively analysed. Follow-up data
      of height, weight and BMI were compared to the Swiss reference population using z
      scores. The correlations between lung function parameters (FEV1, MEF50, VC) and
      age, as well as lung function parameters and growth indices, were calculated.
      Additionally, the same correlations were examined in a cohort with the same
      mutation born 10 years earlier. RESULTS: In the study, cohort growth (height,
      weight and BMI) was significantly below that of the normal Swiss population. A
      significant decline of lung function with age was also found, however, no
      association between lung function and growth could be seen. Compared to an
      earlier cohort, an improved growth over the last decade could be shown but no
      improvement on lung function could be detected. Lung function varied widely in
      both groups. CONCLUSION: In contrast to sequential cross-sectional studies of
      children with CF, the present longitudinal study of children with homozygous for
      the Delta F508 mutation failed to confirm normalisation of growth over time.
      However, compared to the data of children born in the previous decade, improved
      growth was observed.

PMID- 15463855
TI  - Cost of care and clinical condition in paediatric cystic fibrosis patients.
AB  - BACKGROUND: The clinical course of cystic fibrosis (CF) shows considerable
      variation resulting in differences in health care utilisation. We investigated
      important clinical parameters and their relation to costs. METHODS: We collected
      clinical parameters together with health care utilisation of a representative
      paediatric CF population (n=138 patients) attending Hanover Medical School over a
      period of 1 year. 49% of the patients were chronically infected with Pseudomonas
      aeruginosa. Costs were calculated on the basis of the annual individual health
      care utilisation from the perspective of health insurance. RESULTS: Total annual
      expenditure per patient amounted to 23,989 euro (S.D. 18,026), with home drug
      treatment representing the most important single cost factor (47% of total
      costs). While costs rose with age and doubled in the first 18 years, they
      correlated foremost with P. aeruginosa airway colonisation status and lung
      function expressed as FEV(1). Costs of patients with chronic P. aeruginosa
      infection were more than three times higher than of uninfected patients.
      CONCLUSIONS: Health care expenditures for patients with CF vary with the clinical
      course. The variation can be explained to a large extend by clinical parameters.

PMID- 15463856
TI  - Assessment of vitamin K deficiency in CF--how much sophistication is useful?
AB  - BACKGROUND: Due to maldigestion of dietary lipids, fat soluble vitamins are prone
      to malabsorption in cystic fibrosis (CF) patients with pancreatic insufficiency
      (PICF). Routine supplementation of vitamin K(1) in PICF is presently subject of
      discussion. METHODS: Serum vitamin K, prothrombin time, PIVKA-II ('liver marker',
      by two different ELISAs), hydroxyapatite binding capacity (HBC, 'bone marker')
      and ApoE genotypes were measured in 32 PICF patients (age: 7 months to 25 years)
      with (PICFK) or without (PICFN) oral vitamin K(1) supplementation, all receiving
      lipase supplementation, and in 18 healthy controls (C). RESULTS: PIVKA-II was
      positive only in 4/7 PICFN. HBC medians of all groups were 57-60%. HBC values of
      PIVKA-II positive patients were below HBC median of their group. There was no
      correlation between HBC and PIVKA-II. There was no correlation between
      prothrombin time and other measurements. HBC medians with regard to ApoE were
      ApoE2/3 (62.9%)>ApoE3/3 (57.6%)>ApoE3/4+ApoE4/4=(56.65%). CONCLUSIONS: Vitamin K
      deficiency of liver or bone may occur independently. Prothrombin time is an
      insensitive marker. Individuals with ApoE4 allels might be more susceptible to
      osteopenia. As high expenditures are necessary to detect patients at risk,
      routine vitamin K supplementation for all PICF patients appears appropriate.

PMID- 15463857
TI  - Knowledge, interests and educational needs of adults diagnosed with cystic
      fibrosis after age 18.
AB  - BACKGROUND: Little is known about the knowledge, interests, or educational needs
      of those diagnosed with cystic fibrosis (CF) as adults or the extent to which
      they find available information helpful. The purpose of this inquiry was to
      address these gaps. METHODS: A mailed survey, completed by an international
      sample (N=130) recruited through internet sites and CF Centers, collected
      quantitative and qualitative data to address five research questions. A response
      rate of 74.3% was achieved. RESULTS: Most participants (67.4%) said they knew
      little or nothing about CF at diagnosis. Of the 71.5% who indicated they received
      patient education, 26.9% felt they were given 'too little'. At diagnosis, most
      wanted disease-related information about CF. Over time they expressed interest in
      topics related to quality-of-life, such as CF research efforts, alternative
      medicine and employment issues. Three-fourths (75.4%) were active information
      seekers, but 60.2% were less than satisfied with what they found. Qualitative
      responses indicated participants did not 'see themselves' in available materials,
      which many described as 'depressing'. CONCLUSIONS: Medical caregivers must be
      aware of and respond to the unique educational interests and needs of their adult
      diagnosed patients. Additional research is recommended to better understand how
      patient education benefits these adults.

PMID- 15463858
TI  - Major haemoptysis in children with cystic fibrosis: a 20-year retrospective
      study.
AB  - BACKGROUND: Major haemoptysis occurs in approximately 1% of children with cystic
      fibrosis (CF). This report describes management and follow-up of these children
      at a tertiary centre in Australia. METHODS: Retrospective review of medical
      records from 1980-1999. RESULTS: Fifty-one children (45% female) had major
      haemoptysis (102 episodes). Mean age at first episode was 15 years (range 7-19)
      and mean FEV(1) was 56% predicted (range 14-98). Massive life-threatening
      haemoptysis was not confined to those with severe lung disease (FEV1 < 50%
      predicted). Bronchial artery embolisation (BAE) was more likely to be the initial
      treatment for those with massive haemoptysis and chronic recurrent bleeding
      tended to be treated conservatively (P = 0.01). Overall, 52 BAE were performed in
      28 children with an immediate success rate of 98%; 13 children (46%) had repeated
      BAE. Four patients died as a direct result of severe haemoptysis. Mean follow-up
      was 54 months (range 0.5-183). Median survival time (Kaplan-Meier estimate) after
      first haemoptysis was 70 months, with a significantly longer survival for male
      patients independent of age (RR 3.8; 95% CI 1.7-8.8; P = 0.001). Median survival
      time following initial treatment with BAE was longer (103 months) compared to
      conservative treatment (52 months, P = 0.09). CONCLUSIONS: Massive haemoptysis
      was unrelated to the severity of lung disease and was more likely to be treated
      with embolisation. BAE was highly effective, however, 46% of the children
      required re-embolisation at some time, which is similar to the recurrence risk
      for major hemoptysis treated conservatively on longer term follow-up.

PMID- 15463859
TI  - Cytokine modulating effect of ginseng treatment in a mouse model of Pseudomonas
      aeruginosa lung infection.
AB  - The major cause of morbidity and mortality in cystic fibrosis (CF) patients is
      chronic Pseudomonas aeruginosa lung infection. In a mouse model of P. aeruginosa
      lung infection mimicking that in CF patients, the effects of ginseng treatment on
      cytokine responses and the correlation between the changes in cytokine production
      and the lung pathology were studied. Mice were challenged with alginate beads
      containing P. aeruginosa (10(9) CFU/ml). A saline extract of ginseng was injected
      subcutaneously at a dosage of 250 mg/kg of body weight/day for 7 days. Saline was
      used as a placebo control. One week after challenge, a significantly lower
      mortality was found in the ginseng treated group (P < 0.005). The lung cells from
      the ginseng treated group produced more interferon-gamma (IFN-gamma) (P < 0.04)
      and tumor necrosis factor-alpha (TNF-alpha) (P < 0.03) but less interleukin-4 (IL
      4) (P < 0 .02) with a higher ratio of IFN-gamma/IL-4 (P < 0.004) after 6 and/or
      24 h of incubation with specific and non-specific antigens as compared to the
      control group. The ginseng treated splenocytes produced more TNF-alpha (P < 0.03)
      and IFN-gamma (P0.05) than the control spleen cells. Furthermore, a significantly
      milder lung pathology (P < 0.025) and a faster bacterial clearance (P < 0.038)
      from the lungs were also found in the ginseng treated group compared to the
      control group. These results indicate a Th1-like immune response in the mice with
      P. aeruginosa lung infection after 7 days of ginseng treatment, which is an
      important mechanism accounting for ginseng's favorable action. We therefore
      believe that Th1 response might benefit the host with P. aeruginosa lung
      infection and ginseng treatment might be a promising alternative measure for the
      treatment of chronic P. aeruginosa lung infection in CF patients.

PMID- 15463860
TI  - Economic evaluation of Tobramycin nebuliser solution in cystic fibrosis.
AB  - BACKGROUND: The cost effectiveness of inhaled TOBIR tobramycin nebuliser solution
      (TNS) in CF and chronic pulmonary Pseudomonas aeruginosa infection has been shown
      in US but not in European studies. METHODS: An economic evaluation of TNS was
      undertaken in children and adults. Lung function and resource utilisation were
      recorded for 24 months before and during TNS therapy. Interventions were costed.
      RESULTS: Forty-one patients received TNS; 30 of them matched with a paired
      control on usual therapy. TNS cases received more inhaled and IV antibiotics in
      the year before TNS than controls, and were hospitalised more. In the TNS treated
      group mean days in hospital before and after (change) were 32.0, 24.2 (-7.8);
      days on IV antibiotics 55.4, 38.9 (-16.4); total cost 22,102 pounds, 28,394
      pounds (+ 6292 pounds), composed of cost of TNS 0 pounds, 10,010 pounds (+ 10,010
      pounds), cost of hospitalisation 10,897 pounds, 8552 pounds (- 2345 pounds), cost
      of drugs 11,205 pounds, 9832 pounds (- 1374 pounds). In 19 patients aged < 18 the
      change in days hospitalised was -10.7 and days on IVs -20.2. Incremental cost was
      3830 pounds. CONCLUSIONS: TNS was associated with clinically and socially
      important reductions of hospital attendances and parenteral antibiotics. This
      would improve patients' quality of life and reduce interference with work and
      schooling. Its maximal acquisition cost of 10,010 pounds may be reduced by delays
      in prescribing and dispensing, and was offset by savings of approximately 3500
      6200 pounds.

PMID- 15463861
TI  - Neutrophil recruitment and airway epithelial cell involvement in chronic cystic
      fibrosis lung disease.
AB  - The pathological hallmark of cystic fibrosis (CF) chronic inflammatory response
      is the massive neutrophil influx into the airways. This dysregulated neutrophil
      emigration may be caused by the abnormal secretion of chemoattractants by
      respiratory epithelial cells and polarised lymphocyte T-helper response.
      Neutrophils from CF patients have a different response to inflammatory mediators
      than neutrophils from normal subjects, indicating that they are primed in vivo
      before entering the CF airways. CF neutrophils secrete more myeloperoxidase and
      elastase, mobilise less opsonin receptors and release less L-selectin than non-CF
      neutrophils. Moreover, they show altered cytokine production and a dysregulated
      chemotaxis response. Laboratory studies now suggest that CFTR is involved in
      regulating some neutrophil functions and indicate that altered properties of CF
      neutrophils may depend on genetic factors. Current gene therapy approaches are
      targeted to the respiratory epithelium, but many hurdles oppose an efficient and
      efficacious CFTR gene transfer. The possibility of CFTR gene therapy-based
      approach targeting CF neutrophils at the hematopoietic stem cell level is
      discussed.

PMID- 15463862
TI  - Elemental and ion composition of exhaled air condensate in cystic fibrosis.
AB  - BACKGROUND: In cystic fibrosis (CF) the exact ion composition of the airway
      surface fluid is still debated and it is not clear if it differs from healthy
      subjects. The air that we exhale contains small droplets, which are generated by
      shear forces from the airway surface fluid and very likely mirror its ion
      composition. We hypothesized that differences between CF-patients and healthy
      controls would be reflected by differences in their exhaled air. METHODS: In
      nasally collected exhaled breath condensate from 20 children and young adults
      with cystic fibrosis and 20 healthy subjects, the elements and anions were
      determined by optical emission spectroscopy and ion-exchange chromatography.
      RESULTS: The concentrations of the major components Na and Cl- did not differ, Zn
      was higher and NO3- was lower in CF-patients. During a given time period, CF
      patients produced a slightly larger volume of breath condensate and they exhaled
      more Na, K and Zn. Fluoride was detected in half of all samples, whereas copper,
      iron, magnesium, phosphorus and sulfur were present only sporadically, with no
      differences. CONCLUSIONS: These data detail the composition of exhaled breath
      condensate and suggest a similar Na and Cl- concentration in CF-airway surface
      fluid as in healthy subjects.

PMID- 15463863
TI  - Exhaled nitric oxide increases following admission for intravenous antibiotics in
      children with cystic fibrosis.
AB  - BACKGROUND: Lack of standardisation for the measurement of exhaled nitric oxide
      (NO) (FENO) has resulted in conflicting data in cystic fibrosis (CF). The aim of
      this study was to assess whether FENO is a useful non-invasive marker of lung
      disease in CF by assessing the effect of intravenous (IV) antibiotics on FENO.
      METHODS: FENO was measured on line, according to recently published ERS/ATS
      guidelines, using a chemiluminescence analyser together with pulmonary function
      in 14 CF children prior to and following a course of IV antibiotics. RESULTS:
      There was a significant improvement in mean (S.E.M.) % FEV1 from 60.0 (6.3) to
      68.0 (5.4) (P < 0.05) and mean (S.E.M.) % FVC from 66.3 (5.5) to 75.1 (4.9) (P <
      0.01). FENO increased significantly from median (range) 5.8 (2.0-14.3) to 9.2 ppb
      (0.8-25.1) (P < 0.05). There was no correlation between FE(NO) and lung function.
      Subgroup analysis on those with chronic Pseudomonas aeruginosa infection (n = 6)
      demonstrated no significant change in FENO. CONCLUSIONS: Using a flow of 50 ml/s,
      FENO increases following admission for IV antibiotic treatment in children with
      CF but does not correlate with lung function. It is not a useful marker of lung
      diseases in CF, which has implications for clinical practice.

PMID- 15463864
TI  - Shwachman-Kulczycki score and resting energy expenditure in cystic fibrosis.
AB  - BACKGROUND: Disease severity assessed by clinical scores in cystic fibrosis (CF)
      has been a topic of investigation for many years, although a correlation of
      clinical scores with resting energy expenditure (REE) has not been described yet.
      We aimed to assess disease severity as evaluated by the Shwachman-Kulczycki (SK)
      score and to correlate these findings with REE and forced expiratory volume in 1
      s (FEV1). METHODS: Twenty-eight patients performed respiratory function testing
      (FEV1), and assessment of REE with open circuit indirect calorimetry. The SK
      score was evaluated according to general activity, physical examination,
      nutrition and conventional chest X-ray findings. RESULTS: Mean SK score was 75.3
      +/- 15.7. Mean REE was 109.1% of predicted vs. 96.5% predicted in 16 healthy
      subjects (P = 0.002). There was a significant correlation between the SK score
      and REE (P = 0.001), the SK score and FEV1 (P < 0.001) and REE and FEV1 (P =
      0.034). CONCLUSIONS: The correlations between the SK score, REE and FEV1
      demonstrate a close connection between disease severity, caloric requirement and
      lung damage. They confirm the clinical value of the SK score, which is easy to
      assess in a clinical setting.

PMID- 15463865
TI  - Ciprofloxacin-induced renal insufficiency in cystic fibrosis.
AB  - Acute renal insufficiency is known to occur in patients who are taking
      ciprofloxacin, particularly the elderly. We report two young patients with cystic
      fibrosis who presented with acute renal insufficiency after 2-3 weeks of oral
      ciprofloxacin therapy. The incidence of this adverse effect in children and young
      adults who have cystic fibrosis is unknown. Multiple mechanisms for ciprofloxacin
      induced nephrotoxicity have been proposed.

PMID- 15463866
TI  - Cystic fibrosis: presentation with other diseases, the experience in Saudi
      Arabia.
AB  - Simultaneous occurrence of Cystic fibrosis and other inherited diseases or
      congenital anomalies has been rare. This association has never been described
      before in the Arab population. In this report we describe the first report on
      cystic fibrosis in association with other diseases in the same patient such as
      sickle cell disease, Insulin dependant Diabetes mellitus, congenital adrenal
      hyperplasia, cardiac anomalies in twins and Ehler's Danlos syndrome. We also
      evaluate their effects on CF patients and review the literature in this aspect.

PMID- 15463867
TI  - Osteoporosis is cystic fibrosis.

PMID- 15463868
TI  - Role of exercise and nutrition status on bone mineral density in cystic fibrosis.
AB  - BACKGROUND: Exercise has been shown to maintain or increase bone mineral density
      (BMD) in non-CF populations. OBJECTIVES: The purpose of our study was to
      elucidate the relationship between exercise, body composition and dietary intake
      with BMD in an adult CF population with heterogeneous disease severity. DESIGN:
      We measured spinal (L1-4) and femoral (femoral neck) BMD by dual energy X-ray
      absorptiometry (DEXA) in 68 CF adults (24 female, 44 male) with a mean age
      30.8(1.7) and 27.4(1.3) (range 18-55) years. We used the average BMD Z score for
      spine and femoral neck for analyses. Differences in disease severity, exercise
      capacity, physical activity level, dietary intake, body composition, body mass
      index (BMI), glucocorticoid use were correlated with BMD scores. Exercise
      capacity was defined as the maximal amount of oxygen consumed by muscles during
      maximal exercise (Vo2max). Vertebral and non-vertebral fracture rate were also
      recorded. RESULTS: Fifty-seven patients were identified with low BMD (Z score < 
      1). Multiple linear regression identified exercise capacity and BMI as
      significant predictors of BMD. Later diagnosis of CF was also associated with low
      adult BMD. CONCLUSIONS: Low BMD is common in adult CF patients. Exercise capacity
      and BMI are predictors of low BMD.

PMID- 15463869
TI  - Treatment of urinary incontinence in cystic fibrosis.
AB  - BACKGROUND: Urinary incontinence (UI) is a newly recognised problem in cystic
      fibrosis. Whilst prevalence is well documented, there are no reports of
      assessment and treatment of the problem. METHODS: A previous study reports the
      prevalence of UI in women with CF to be 51/75 (68%). Nineteen women subsequently
      requested help for the problem and were referred to a physiotherapist
      specialising in women's health. A digital assessment was performed to measure
      pelvic floor muscle strength and endurance. An individualised programme of pelvic
      floor muscle exercises (PFME) was taught based on the assessment. A questionnaire
      addressed issues of assessment and treatment. RESULTS: 12 women were assessed.
      The median (range) age, FEV1% predicted and BMI were 20.9 (19.3-46.1) years, 45.9
      (14.8-82.7) and 20.5 (16.1-26.0), respectively. The median strength of the pelvic
      floor muscle was moderate (Oxford Scale grade 3) with a hold time (endurance) of
      5 s. At reassessment (median time 13.1 weeks), there was an improvement in
      endurance (P = 0.04), with no change in strength. This was supported by a
      subjective improvement in symptoms. Patients found the exercises were difficult
      to perform, difficult to fit into their treatment programme and adherence was
      poor. CONCLUSIONS: PFME are effective at improving endurance and reducing leakage
      over the short-term. Women are reluctant to be assessed and the CF team should
      provide support and encouragement with treatment. Long-term outcome and the
      mechanisms of UI in this group of patients need further evaluation.

PMID- 15463870
TI  - Effects of creatine supplementation in cystic fibrosis: results of a pilot study.
AB  - BACKGROUND: The CF transmembrane conductance regulator (CFTR), whose mutations
      cause cystic fibrosis (CF), depends on ATP for activation and transport function.
      Availability of ATP in the cell and even more in specific cellular
      microcompartments often depends on a functional creatine kinase system, which
      provides the 'energy buffer' phosphocreatine. Creatine supplementation has been
      shown to increase phosphocreatine levels, thus promoting muscle growth and
      strength in athletes and having protective effects in neuromuscular disorders.
      AIM: To test clinically, if creatine supplementation improves maximal isometric
      muscle strength (MIMS), lung function and CFTR channel activity in patients with
      CF, and to determine enzymatic activity of creatine kinase in respiratory
      epithelial cells. METHODS: In an open-label pilot study 18 CF patients (8-18-year
      old) with pancreatic insufficiency and mild to moderate lung disease received
      daily creatine supplementation during 12 weeks. Patients were monitored during 24
      36 weeks. Enzymatic activity of creatine kinase was measured in primary
      epithelial cell cultures. RESULTS: After creatine supplementation, there was no
      change in lung function and sweat electrolyte concentrations, possibly due to the
      very low creatine kinase activities detected in respiratory epithelia. However,
      the patients consistently showed significantly increased MIMS (18.4%; P <
      0.0001), as well as improved general well-being, as assessed by a standardized
      questionnaire. Except for one patient with transient muscle pain, no side effects
      were reported. CONCLUSIONS: Our pilot study suggests, that creatine
      supplementation should be further evaluated as a possible clinically beneficial
      adjuvant therapy for patients with CF to increase muscle strength, body-weight
      and well-being.

PMID- 15463871
TI  - DNase in stable cystic fibrosis infants: a pilot study.
AB  - OBJECTIVE: To assess the feasibility of measuring short-term effects of inhaled
      recombinant human deoxyribonuclease (rhDNase, Pulmozyme on lung function, pulse
      oximetry and symptom scores in infants and toddlers with stable cystic fibrosis.
      DESIGN: open-label randomized placebo controlled cross-over pilot study. PATIENTS
      AND METHODS: We treated nine CF patients (0.7-1.9 years) with nebulised rhDNase
      (2.5 mg) and NaCl 0.9% (10 ml) via jet nebulizer cross-over once daily during 2
      week treatment blocks. Measurements were performed at baseline and after
      treatment blocks and consisted of lung function tests (plethysmography and tidal
      rapid thoraco-abdominal compression technique), overnight pulse oximetry, and
      daily symptom scores. RESULTS: DNase treatment and the different assessments were
      well tolerated by all children and their parents. Lung function showed increased
      airway patency after treatment with rhDNase (P < 0.001), but not after NaCl 0.9%.
      Overnight pulse oximetry and daily symptom scores did not change during the study
      period. CONCLUSIONS: This pilot study indicates that objective assessment of the
      effects of rhDNase is feasible in infants with CF who have little or no
      respiratory symptoms. Our results warrant a larger randomized placebo-controlled
      trial.

PMID- 15463872
TI  - Increased expression of Interleukin-13 but not Interleukin-4 in cystic fibrosis
      patients.
AB  - BACKGROUND: Many patients with cystic fibrosis (CF) suffer from allergic disease,
      which can complicate treatment of CF lung disease. Interleukin (IL)-4 and IL-13
      have been shown to be important mediators in allergic disease. OBJECTIVE: To
      investigate the role of IL-4 and IL-13 in allergic and non-allergic CF patients.
      METHODS: Expression of IL-4 and IL-13 mRNA was investigated in peripheral blood
      mononuclear cells (PBM) of seven CF patients with allergy, of six patients
      without allergy and of nine healthy subjects as well as in BAL cells of four
      patients and of all controls. PBM from six patients were incubated with
      recombinant human IL-13 or human antiIL-13 antibody without and with LPS
      stimulation and TNFalpha levels were measured by ELISA. RESULTS: IL-13 mRNA
      expression was increased in allergic and non-allergic patients compared to
      controls. No significant difference in IL-4 expression could be found between
      patients and controls. Addition of IL-13 decreased TNFalpha in PBM culture
      supernatants. CONCLUSION: Our data suggest that IL-13 rather than IL-4 might play
      an important role in both allergic and non-allergic CF patients. IL-13 might also
      compromise host defence by decreasing TNFalpha production.

PMID- 15463873
TI  - Improved glutathione status in young adult patients with cystic fibrosis
      supplemented with whey protein.
AB  - BACKGROUND: The lung disease of cystic fibrosis is associated with a chronic
      inflammatory reaction and an over abundance of oxidants relative to antioxidants.
      Glutathione functions as a major frontline defense against the build-up of
      oxidants in the lung. This increased demand for glutathione (GSH) in cystic
      fibrosis may be limiting if nutritional status is compromised. We sought to
      increase glutathione levels in stable patients with cystic fibrosis by
      supplementation with a whey-based protein. METHODS: Twenty-one patients who were
      in stable condition were randomly assigned to take a whey protein isolate
      (Immunocal, 10 g twice a day) or casein placebo for 3 months. Peripheral
      lymphocyte GSH was used as a marker of lung GSH. Values were compared with
      nutritional status and lung parameters. RESULTS: At baseline there were no
      significant differences in age, height, weight, percent ideal body weight or
      percent body fat. Lymphocyte GSH was similar in the two groups. After
      supplementation, we observed a 46.6% increase from baseline (P < 0.05) in the
      lymphocyte GSH levels in the supplemented group. No other changes were observed.
      CONCLUSION: The results show that dietary supplementation with a whey-based
      product can increase glutathione levels in cystic fibrosis. This nutritional
      approach may be useful in maintaining optimal levels of GSH and counteract the
      deleterious effects of oxidative stress in the lung in cystic fibrosis.

PMID- 15463875
TI  - Quality of life in cystic fibrosis: the impact of gender, general health
      perceptions and disease severity.
AB  - BACKGROUND: Disease progression in cystic fibrosis (CF) is marked by
      deterioration across a number of physiological systems. In addition, there is
      evidence that females have a worse prognosis than males. The current work
      assesses the impact of both these factors on health related quality of life
      (HRQoL). METHODS: Two hundred and twenty-three adolescents and adults completed
      the cystic fibrosis quality of life (CFQoL) questionnaire with a further 185
      approached and not responding by non-completion of the questionnaire. The CFQoL
      is divided into nine domains: physical, social, treatment, chest symptoms,
      emotional functioning, concerns for the future, relationships, body image, and
      career. Measurement of objective clinical status included, body mass index (BMI),
      and percentage of predicted forced expiratory volume in one second (FEV1).
      General health perceptions (GHP) were also measured. RESULTS: Patients were sub
      divided by gender and disease severity (mild > 70% FEV1, moderate 40-69% and
      severe < 40%). Factorial analysis of variance indicated significant main effects
      for FEV1 (F = 587.98, P < or = 0.001) and BMI (F = 17.29, P < or = 0.001) as a
      function of disease severity. Post hoc tests revealed significant two-group
      differences for FEV1 and BMI between disease severity groups. No differences were
      observed for gender across FEV1 or BMI. Differences emerged across most CFQoL
      domains for disease severity, with the exception of concerns for the future,
      which was consistently low throughout. Gender differences emerged for chest
      symptoms, emotional functioning, concerns for the future, body image and career.
      With the exception of body image, females exhibited poorer HRQoL. Pearson
      correlations indicated that females' perception of health was more closely
      related to clinical status than males. CONCLUSIONS: Disease severity has an
      impact on HRQoL in adolescents and adults with CF. Some differences emerged
      between males and females, with females generally reporting poorer HRQoL.
      Evidence indicated that males and females perceived their health status
      differently, with females having a more accurate perception of objective clinical
      health status.

PMID- 15463874
TI  - Different opinions of physicians on the importance of measures to prevent
      acquisition of Pseudomonas aeruginosa from the environment.
AB  - BACKGROUND: Since chronic infection with mucoid Pseudomonas aeruginosa (PA) is
      associated with deteriorating lung function, many parents of young children with
      cystic fibrosis (CF) fear the first PA positive throat swab as a milestone in the
      progression of the disease. To reduce the risk of PA acquisition from the
      environment, they perform preventive measures at home or outdoors. METHODS: In an
      attempt to evaluate the attitude of CF physicians towards these measures and the
      respective consulting practice, we mailed a questionnaire to all 65 certified
      paediatric CF centres in Germany. RESULTS: Physicians from 54 (83%) CF clinics
      replied. They expressed widely different ideas about the impact of the
      environment for the acquisition of P. aeruginosa, and recommended a large
      spectrum of preventive measures. Some physicians proposed only few precautions,
      which focussed on the prevention of cross-infection between patients, whereas
      others suggested prevention of any contact with moist or wet places, e.g. use
      different toothbrushes for mornings and evenings, or do without air-conditioning
      in the car. CONCLUSIONS: CF physicians have different opinions on the risk of PA
      acquisition from the environment. Doctors who recommend strict precautions could
      engender a parental fear of a ubiquous threat from invisible bacteria. The
      resulting extended safety measures might impair the family's quality of life.

PMID- 15463876
TI  - Cystic fibrosis and neonatal calcified scrotal masses.
AB  - We report a case of an infant who presented with failure to thrive and in whom
      the identification of calcified scrotal masses led us to the diagnosis of cystic
      fibrosis.

PMID- 15463877
TI  - Bronchial to subclavian shunt in a CF patient. A potential pitfall for
      embolization.
AB  - Bronchial artery embolization is a well accepted and widely used technique in the
      management of massive haemoptysis in cystic fibrosis (CF). It can be a complex
      procedure requiring a deep knowledge of the bronchial artery anatomy including
      the possible bronchial anastomoses. We report a case of complex vascular anatomy
      of the left bronchial artery with multiple anastomoses with the ipsilateral
      subclavian artery as cause of non-attempted embolization.

PMID- 15463879
TI  - Foreword.

PMID- 15463878
TI  - Burkholderia cepacia complex infection in adult patients with cystic fibrosis--is
      early eradication possible?

PMID- 15463880
TI  - Dietary intakes in adult patients with cystic fibrosis--do they achieve
      guidelines?
AB  - BACKGROUND: Most patients with cystic fibrosis (CF) require a higher energy and
      protein intake than their healthy peer group. There are few data on dietary
      intakes of adult patients. The aim of this study was to determine nutritional
      intakes in an adult population with CF. The impact of nutritional intervention
      and disease on macronutrient intake was examined. METHODS: Retrospective cross
      sectional analysis of 94 unweighed food diaries at annual review (1995-2000).
      Energy and protein intakes were compared to the estimated average requirement
      (EAR) for energy and reference nutrient intake (RNI) for protein. The effect of
      diet alone, oral supplements, enteral tube feeding, and cystic fibrosis related
      diabetes (CFRD), on macronutrient intake was examined and impact of pancreatic
      sufficency (PS) and lung transplantation. RESULTS: Mean energy and protein
      intakes approached recommended CF guidelines, but in 72% of assessments these
      values were not achieved. Mean energy and protein intakes for patients on diet
      alone and protein intake for those with CFRD failed to meet recommendations. Oral
      supplementation and enteral tube feeding regimens increased energy and protein
      intake above recommended levels. No group achieved 40% total energy from fat.
      Patients receiving enteral tube feeds had the highest mean energy and protein
      intakes but lowest body mass index (BMI) and lung function. CONCLUSION: Adequate
      mean energy and protein intakes in adult patients with CF mask subgroups of
      patients who fail to meet recommendations ie. diet alone, diabetic. Oral
      supplementation and enteral tube feeding increase energy and protein intake but
      fail to achieve an adequate BMI level in subjects with a decreased clinical
      status. Individual nutritional assessment remains essential.

PMID- 15463881
TI  - Improved outcomes of patients with cystic fibrosis admitted to the intensive care
      unit.
AB  - BACKGROUND: Invasive mechanical ventilation (IMV) has been previously associated
      with a poor outcome for patients with cystic fibrosis (CF), but with improved
      survival and the availability of lung transplantation intensive care unit (ICU)
      admission is being increasingly considered. This study aimed to review the
      outcomes of adult CF patients admitted to ICU, and to identify factors that may
      have influenced outcomes. METHODS: A retrospective audit was conducted of CF
      patients admitted to ICU. Anthropometric data, spirometry, nutritional status,
      sputum microbiology, arterial blood gas tensions, and mode of ventilation used
      were recorded. Immediate and 1-year survival and lung transplantation utilisation
      were recorded. RESULTS: Twenty patients were admitted to ICU and nine (45%)
      survived to hospital discharge. Five of the nine survivors had potentially
      reversible conditions. Four patients admitted with respiratory exacerbations
      alone who survived, were maintained on non-invasive ventilation (NIV). The
      relative risk of deaths for patients with a BMI < 18 and a FEV1 < 24% predicted
      were 3.25 (1.27-3.25), and 3.68 (1.11-16.33), respectively. CONCLUSIONS: The
      outcome of patients with CF admitted to ICU has improved, with 45% of the
      patients in this study surviving to hospital discharge. Five of these survivors
      underwent successful lung transplantation. Long-term use of NIV post discharge
      may have contributed to this favourable outcome. A BMI < 18 and FEV1 < 24%
      predicted were associated with a significantly higher relative risk of death.

PMID- 15463882
TI  - Diagnosis of cystic fibrosis in adults with diffuse bronchiectasis.
AB  - We assessed the contribution of the sweat test, genotyping and nasal potential
      difference (NPD) in the diagnosis of cystic fibrosis (CF) in adults with diffuse
      bronchiectasis (DB). Among 601 adults referred for DB from 1992 to 2001, 46 were
      diagnosed with CF. The sweat test was positive in 37 patients and normal or
      intermediate in nine patients. Two CF mutations were identified in 18 patients
      (39%) by screening for 31 mutations and in 36 patients (78%) after complete
      genetic analysis. NPD was suggestive of CF in 71% of the patients. The
      combination of the sweat test and genetic analysis led to the diagnosis of CF in
      45 patients. In the nine patients with normal or intermediate sweat test, the
      diagnosis was confirmed by screening for 31 mutations in five, by complete
      genetic screening in three, and by NPD in the remaining patient. Searching for CF
      should start with sweat test. If the sweat test is normal or intermediate,
      screening for 31 mutations may help to diagnose CF. A complete genetic analysis
      is indicated when only one mutation is detected and/or when other clinical
      features, such as obstructive azoospermia or pancreatic insufficiency, are
      suggestive of CF. NPD measurement is indicated in controversial cases.

PMID- 15463883
TI  - Effect of nebulized colistin sulphate and colistin sulphomethate on lung function
      in patients with cystic fibrosis: a pilot study.
AB  - BACKGROUND: Pulmonary administration of colistin is one of the antimicrobial
      treatments used in Cystic Fibrosis (CF) patients chronically infected with
      Pseudomonas aeruginosa. Dry powder inhalation of colistin may be an attractive
      alternative to nebulization of colistin. However, nebulized colistin can cause
      bronchoconstriction in CF patients. Therefore, in the progress of developing a
      dry powder formula, the choice of the inhaler and its contents should be guided
      by optimal efficacy and the least possible side effects. To investigate the side
      effects, a study was initiated to compare the tolerability of colistin sulphate
      to colistin sulphomethate per nebulization in CF-patients. METHODS: Nine CF
      patients chronically infected with P. aeruginosa participated in a double blind,
      randomized cross over study. On two visits to the outpatient clinic, patients
      were submitted to either nebulized colistin sulphate or colistin sulphomethate
      solution. Lung function tests were performed immediately before and 15 and 30 min
      after nebulization. RESULTS: Nebulization of colistin sulphate caused a
      significant larger mean decrease in lung function compared to nebulized colistin
      sulphomethate. A significant decrease in mean changes (SD) in FEV1 at 30 min and
      FVC at 15 and 30 min after nebulization compared to baseline of -7.3% (8.6%), 
      5.7% (7.3%) and -8.4% (7.5%) respectively was seen after colistin sulphate
      nebulization compared to colistin sulphomethate (P < 0.05). Seven patients were
      not able to complete the nebulization of colistin sulphate because of throat
      irritation and severe cough. CONCLUSION: Based on these results it was concluded
      that inhalation with nebulized colistin sulphate is not suitable for treatment of
      CF patients chronically infected with P. aeruginosa. Colistin sulphomethate is
      the drug of choice for pulmonary administration of colistin.

PMID- 15463884
TI  - Validation of the Dutch cystic fibrosis questionnaire (CFQ) in adolescents and
      adults.
AB  - BACKGROUND: This study assesses the reliability and validity of the Dutch version
      of a disease-specific measure of health-related quality of life (HRQOL) for
      adolescents and adults with CF (CFQ-14+). The 47-item CFQ-14+ covers nine
      domains, three symptom scales and one health perception scale. METHODS: To assess
      psychometric characteristics of the CFQ-14+, cross-sectional (homogeneity,
      discriminative and construct validity) and test-retest designs were used. Eighty
      four adolescents and adults with CF (mean age: 21.4 years, range 14.0-46.5 years)
      and a wide range of lung function (mean FEV1: 59.9% predicted, range 15-121%)
      completed the questionnaire during a routine visit. RESULTS: Internal consistency
      was acceptable for most domains of the CFQ-14+ (alpha = 0.43-0.92) and test
      retest reliability was high for all domain scores (0.72-0.98). Several domains of
      the CFQ-14+ were able to differentiate between individuals with varying disease
      severity and between nourished and malnourished patients. Construct validity of
      the questionnaire was fair, with moderate to strong correlation between
      physically orientated domains and pulmonary function (rs = 0.36-0.62).
      CONCLUSION: The results demonstrate that the CFQ-14+ questionnaire is a well
      validated measure of HRQOL assessment in adolescents and adults with CF.

PMID- 15463885
TI  - Genotyping of Pseudomonas aeruginosa in cystic fibrosis suggests need for
      segregation.
AB  - BACKGROUND: Emerging resistance of Pseudomonas aeruginosa within cystic fibrosis
      (CF) populations is attributed to antibiotic pressure and spread of transmissible
      strains. We describe increasing resistance of P. aeruginosa isolates, resulting
      in the identification of two multiresistant strains and their impact on
      morbidity. METHODS: Susceptibility reports of all P. aeruginosa isolates since
      1998 in our unit were reviewed. Isolates were submitted for genomic finger
      printing by pulsed-field gel electrophoresis. Clinical measures and the
      consumption of treatment resources were compared between those harbouring
      resistant organisms and those with sensitive strains. RESULTS: Analysis of 407
      reports from 43 patients revealed isolation of multiresistant (MR) organisms
      increased during 1999. Those harbouring MR strains consumed more resources than
      non-MR. Strain typing showed a new 'Sheffield' strain in seven patients (100%
      MR), and the 'Liverpool' strain in 10 patients (40% MR). Individuals in these
      groups consumed significantly more resources than 23 patients with unique,
      susceptible strains (4% MR). DISCUSSION: Increasing resistance in isolates of P.
      aeruginosa may herald the arrival of a transmissible strain in CF Units which
      though sometimes sensitive, may become multiply resistant and require more
      intensive treatment. We now segregate those with transmissible strains from each
      other and from those with unique strains.

PMID- 15463886
TI  - Beta-defensins and LL-37 in bronchoalveolar lavage fluid of patients with cystic
      fibrosis.
AB  - BACKGROUND: The antimicrobial peptides human beta-defensin 1 and 2 (hBD-1 and 2)
      and the cathelicidin LL-37/hCAP-18 are key factors in innate immune responses of
      the respiratory tract. The aim of this study was to determine the concentrations
      of these peptides in airway surface fluid of CF patients with mild lung disease.
      METHODS: We measured the concentrations of hBD-1, hBD-2, and LL-37 in
      bronchoalveolar lavage fluid of 20 patients (5-34 years) participating in the
      prospective BEAT-study (bronchoalveolar lavage for the evaluation of anti
      inflammatory treatment) using an immuno-dot blot-assay. RESULTS: All three
      peptides could be detected in lavage fluid of the study population. Increased
      levels of inflammatory markers in bronchoalveolar lavage fluid were associated
      with elevated concentrations of LL-37/hCAP-18 (total cell count, P = 0.006;
      relative neutrophil count, P = 0.002). Deterioration of lung function, measured
      by MEF25 (maximal flow rate at 25% of residual forced vital capacity), correlated
      with decreased hBD-2 (P = 0.026), but increased LL-37/hCAP-18 concentrations (P =
      0.016). CONCLUSIONS: The data suggest that concentrations of antimicrobial
      peptides are correlated with severity of CF lung disease: Levels of LL-37/hCAP-18
      are associated with bronchial inflammation and, therefore disease severity,
      whereas decreased levels of beta-defensins in advanced lung disease likely
      contribute to a secondary defect of the local host defense.

PMID- 15463887
TI  - Prevalence of pain in adults with cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) may strongly condition the life of affected
      people. CF may be associated with relevant painful conditions caused by
      complications of the illness and also by therapy itself, which may represent an
      additional load of suffering. This study was aimed at evaluating the prevalence
      of pain symptoms in adult CF patients, if they are noticed and treated, and the
      influence of pain symptoms on patients' life. METHOD: Using a questionnaire, we
      examined 239 adults with CF (17% of the whole Italian adult CF population).
      RESULTS: We found a high prevalence of painful episodes among CF adult patients,
      as for both intensity and frequency. In a 2 months period 32.6% of patients
      experienced episodes of pain described as intense to severe, and 29.7% had more
      than 10 occurrences of pain in the same location. Headache, gastric pain and
      backache were the most frequently reported kind of pain. 59.8% of subjects
      perceived pain episodes as the cause of unfavorable effects on their life. Only
      42.6% of those with pain asked a CF center physician for help and another 3.5% a
      general practitioner. CONCLUSION: Painful symptoms can be the cause of a
      worsening of the quality of life for adults with CF; the relevance of pain in CF
      adult patients may often be underestimated; the assessment of pain should be
      routinely performed as a part of care in CF centers.

PMID- 15463888
TI  - Severe CF manifestation with anaemia and failure to thrive in a 394delTT
      homozygous patient.
AB  - We report on a 394delTT homozygous cystic fibrosis (CF) patient with severe
      disease progression. At the diagnosis made at the age of 2.5 months, he suffered
      from macrocytic anaemia as the most prominent symptom of CF, malnutrition,
      hypoproteinaemia and profound hypoalbuminaemia, but demonstrated only minimal
      pulmonary symptoms. Abnormal sweat chlorides confirmed the diagnosis of CF.
      Severe pulmonary and liver disease caused death after 6 years.

PMID- 15463890
TI  - "Maintaining the horizontal line": early intervention and prevention of CF lung
      disease.

PMID- 15463889
TI  - Eradication of pulmonary methicillin-resistant staphylococcus aureus (MRSA) in
      cystic fibrosis with linezolid.

PMID- 15463891
TI  - Early intervention and prevention of lung disease in cystic fibrosis: a European
      consensus.
AB  - In patients with cystic fibrosis (CF), early intervention and prevention of lung
      disease is of paramount importance. Principles to achieve this aim include early
      diagnosis of CF, regular monitoring of the clinical status, various hygienic
      measures to prevent infection and cross-infection, early use of antibiotic
      courses in patients with recurrent or continuous bacterial colonisation and
      appropriate use of chest physiotherapy.

PMID- 15463892
TI  - Clinical outcome of Burkholderia cepacia complex infection in cystic fibrosis
      adults.
AB  - BACKGROUND: The Burkholderia cepacia complex (BCC) is one of the most important
      groups of organisms infecting cystic fibrosis (CF) patients. The aim of the study
      was to examine how infection with BCC affects clinical outcome. METHODS: Nineteen
      CF adults infected with BCC and 19 controls infected with Pseudomonas aeruginosa
      were studied over a 4-year period. The best forced expiratory volume in 1 s
      (FEV(1)) and body mass index (BMI) for each year were recorded and annual rate of
      decline calculated. RESULTS: The BCC infected group displayed a significantly
      greater reduction of FEV(1) and BMI compared to the P. aeruginosa infected group
      (p=0.001 and p=0.009, respectively). Sixteen patients infected with a single
      Burkholderia cenocepacia strain had a significantly greater rate of FEV(1)
      decline compared to those infected with Burkholderia multivorans (n=3) or P.
      aeruginosa (p=0.01 and p<0.0001, respectively). The rate of BMI decline was
      significantly greater in patients infected with B. cenocepacia compared to those
      with P. aeruginosa (p=0.007), but not significantly different in those with B.
      multivorans (p=0.29). CONCLUSION: BCC infection is associated with an accelerated
      decline in pulmonary function and BMI. Infection with a single B. cenocepacia
      strain was associated with a more rapid decline in lung function than those
      infected with either B. multivorans or P. aeruginosa.

PMID- 15463893
TI  - Purinergic signaling underlies CFTR control of human airway epithelial cell
      volume.
AB  - BACKGROUND: Loss of cystic fibrosis transmembrane conductance regulator (CFTR)
      function in cystic fibrosis (CF) causes dysregulation of multiple ion channels,
      water channels, and acid-base transporters in epithelia. As such, we hypothesized
      that dysregulation of many critical ion channels and transporters may cause
      defects in human airway epithelial cell volume regulation. METHODS: Cell volume,
      regulatory volume decrease, and its regulation was assessed in real-time via
      Coulter Counter Multisizer III-driven electronic cell sizing in non-CF, CF, and
      CFTR-complemented CF human airway epithelial cells. SPQ halide fluorescence assay
      of hypotonicity-induced chloride efflux provided indirect validation of the cell
      volume assays. RESULTS: CFTR, via autocrine ATP signaling, governs human airway
      epithelial cell volume regulation. Non-CF cells and wild-type (WT)-CFTR
      transfected CF cells had normal regulatory volume decrease (RVD) responses that
      were attenuated by blockade of autocrine and paracrine purinergic signaling. In
      contrast, parental IB3-1 CF cells or IB3-1 cells expressing CFTR mutants
      (DeltaF508, G551D, and S1455X) failed to RVD. CF cell RVD was rescued by agonists
      to P2Y G protein-coupled receptors and, more robustly, by agonists to P2X
      purinergic receptor channels. CONCLUSIONS: Loss of CFTR and CFTR-driven autocrine
      ATP signaling may underlie defective cell volume regulation and dysregulated ion,
      water, and acid-base transport in CF airway epithelia.

PMID- 15463894
TI  - Glutathione and glutathione peroxidase in sputum samples of adult patients with
      cystic fibrosis.
AB  - BACKGROUND: Reduced glutathione (GSH) is a major antioxidant in the lung. In
      cystic fibrosis (CF) patients, extracellular GSH levels of lower airways,
      obtained by bronchoalveolar lavage (BAL), were reported to be lower than non-CF
      individuals. METHODS: Upper airway secretions of stable adult CF patients (29
      spontaneous and 13 induced sputum) and non-CF individuals (14 healthy and 12
      asthmatics; all induced sputum) were analyzed for total glutathione (i.e. the sum
      of reduced, GSH, and oxidized, GSSG, forms), GSH and GSSG levels by enzymatic
      kinetic assay. RESULTS: In CF, both spontaneous and induced sputum samples were
      comparable in total glutathione levels which were surprisingly high (median
      concentration of 9.2 (range 1.4-65.2) and 11.6 (1.1-69.8) microM, respectively).
      In non-CF individuals, total glutathione levels were significantly lower (healthy
      2.8 (1.0-12.3), asthmatics (5.3 (1.3-19.2) microM; p<0.001, both vs. CF). In CF,
      more than 90% of total glutathione was represented by GSH, whereas in non-CF
      controls, GSH made up less than 50% of total glutathione (p<0.001). CONCLUSIONS:
      In contrast to BAL, CF sputum contains high levels of GSH. Sputum induction is a
      potentially useful procedure to monitor antioxidant levels in upper airways of CF
      patients.

PMID- 15463895
TI  - Hepatic iodothyronine deiodinase type 1 activity is decreased in two DeltaF508
      cystic fibrosis mouse models.
AB  - BACKGROUND: Abnormal thyroid status has been reported in cystic fibrosis (CF)
      patients, and this can possibly be correlated to neuromuscular symptoms.
      Iodothyronine deiodinase type 1 (D1) activity is an important determinant of
      thyroid status, and we chose to investigate D1 activity in CF liver. METHODS: We
      have measured hepatic D1 activities in two DeltaF508 CF mouse models. RESULTS:
      Hepatic D1 activity was significantly reduced by 31% to 48% in homozygous
      DeltaF508 mice compared with wild-type genotypes. CONCLUSIONS: A decreased
      hepatic D1 activity could be the biochemical basis of some of the abnormal
      thyroid parameters observed in cystic fibrosis patients.

PMID- 15463896
TI  - Decreased interleukin-18 expression in BAL cells and peripheral blood mononuclear
      cells in adult cystic fibrosis patients.
AB  - Lymphocytes from cystic fibrosis (CF) patients secrete less interferon-gamma (IFN
      gamma) upon stimulation compared to controls. Expression of interleukin (IL)-18
      as an IFN-gamma inducing factor and of IL-10 as an IL-18 inhibiting factor were
      determined in bronchoalveolar lavage (BAL) cells from CF patients (n=5) and from
      normal control subjects (n=9) as well as in peripheral blood mononuclear cells
      (PBMC) from patients (n=12) and from control subjects (n=9) with RT-PCR. IL-18
      and IL-10 serum protein levels were measured using ELISA. BAL cells and PBMC of
      CF patients expressed significantly less IL-18 compared to controls (p<0.05).
      There was no significant difference for IL-10 in BAL cells. However, PBMC from
      patients expressed significantly more IL-10 mRNA (p<0.05). IL-18 serum protein
      levels were decreased in the patient group, whereas IL-10 serum concentrations
      were elevated. Stimulation with rhIL-10 reduced IL-18 expression in PBMC from CF
      patients. Decreased IL-18 expression in CF patients may contribute to decreased
      IFN-gamma production. IL-10 may contribute to inhibit IL-18 expression in PBMC in
      CF.

PMID- 15463897
TI  - 'Cepacia syndrome' with Burkholderia multivorans, 9 years after initial
      colonization.
AB  - A 16-year-old boy with cystic fibrosis developed 'cepacia syndrome' 9 years after
      the first isolation of Burkholderia multivorans. It is important to recognise
      that 'cepacia syndrome' is not restricted to those infected with genomovar type
      III strains and that rapid, irreversible clinical decline can occur many years
      after the 1st isolation of Burkholderia cepacia complex (Bcc).

PMID- 15463898
TI  - Cystic fibrosis presenting as metabolic alkalosis in a boy with the rare D579G
      mutation.
AB  - We report on a 10-month-old boy with hypotonic dehydration and metabolic
      alkalosis. Sweat test was borderline and genetic analysis was negative for common
      mutations. Analysis of the whole coding regions of the CFTR gene revealed the
      rare mutation D579G in homozygosity.

PMID- 15463899
TI  - Storing CF Tissues.

PMID- 15463900
TI  - Vitamin A levels in patients with CF are influenced by the inflammatory response.
AB  - BACKGROUND: Serum vitamin A, normally depressed in inflammatory conditions, is
      frequently low in people with CF. Vitamin A is important in respiratory
      epithelial regeneration and repair. We hypothesised that serum vitamin A would be
      associated with inflammation and disease severity. METHODS: Serum vitamin A (as
      retinol), C-reactive protein (CRP), vitamin E, 25-hydroxy vitamin D (25OHD), 1,25
      dihydroxy vitamin D (1,25(OH)(2)D), weight, and lumbar spine bone mineral density
      (LSBMD) were measured in 138 subjects with CF (5-56 years) and 138 control
      subjects (5-48 years). FEV(1), presence of CF liver disease (CFLD) and hospital
      admissions were recorded in those with CF. RESULTS: Serum vitamin A level was
      lower in CF subjects than in controls (mean, 95% CI: 1.29, 1.0-1.37 vs. 1.80, 1.7
      1.87 micromol/l, p < 0.0001), and inversely correlated with CRP (r(s) = -0.37, p
      < 0.0001). CF subjects with low vitamin A (45%) level had poorer FEV(1), weight z
      score, LSBMD z-score, and higher CRP compared with those with normal levels. In
      the CF group CRP, vitamin E, 1,25(OH)(2)D, presence of CFLD, admissions, and age
      were associated with vitamin A level. CONCLUSIONS: Serum vitamin A is negatively
      associated with CRP in subjects with CF, consistent with normal population
      studies. It is important to distinguish between low serum vitamin A associated
      with the inflammatory response and that due to poor nutritional stores. The role
      of vitamin A in CF warrants further study, in the contexts both of chronic
      recurrent inflammatory disease and acute pulmonary exacerbation.

PMID- 15463901
TI  - Antibiograms of resistant Gram-negative bacteria from Scottish CF patients.
AB  - BACKGROUND: Over a 19-month pilot phase, 93 multiply resistant Gram-negative
      isolates from Scottish cystic fibrosis patients were sent to a referral
      laboratory for further investigation. METHODS: In common with the referring
      diagnostic laboratories, disc diffusion testing was carried out. Antibiotic
      susceptibility testing was also established by MIC methodology. NCCLS methods
      were used throughout. Twenty antibiotics were tested. RESULTS: Comparing disc
      diffusion results against MIC results, there were 167 (14%) major errors. By MIC,
      Pseudomonas aeruginosa (n = 59), Stenotrophomonas maltophilia (n = 16),
      Burkholderia cepacia (n = 10) and Alcaligenes xylosoxidans (n = 7) were
      susceptible to 18%, 11%, 4% and 35% of the antibiotics tested, respectively.
      Colistin and tobramycin were the most active agents against P. aeruginosa with
      60% and 49%, respectively, testing susceptible. Minocycline and gentamicin were
      most active against S. maltophilia with 58% and 18%, respectively, testing
      susceptible. B. cepacia were most susceptible to co-trimoxazole (10%) and
      ciprofloxacin (10%). Five and six of the seven A. xylosoxidans isolates were
      susceptible to piperacillin and imipenem, respectively. CONCLUSIONS: Improved
      methods for susceptibility testing of such clinical isolates need to be employed
      in routine diagnostic laboratories. Levels of resistance in referred isolates
      were very high and similar to those described in the USA.

PMID- 15463902
TI  - Molecular epidemiology of Pseudomonas aeruginosa, Burkholderia cepacia complex
      and methicillin-resistant Staphylococcus aureus in a cystic fibrosis center.
AB  - Chronic pulmonary infections caused by Pseudomonas aeruginosa, Burkholderia
      cepacia complex and Staphylococcus aureus are responsible for most of the
      morbidity and mortality of patients with cystic fibrosis (CF). Little is known
      about the routes of transmission of these pathogens from environmental or
      hospital sources to the patients. We hypothesised that strains of P. aeruginosa,
      B. cepacia complex and methicillin-resistant S. aureus (MRSA) are nosocomially
      acquired by CF patients. Bacterial isolates were obtained from 164 patients
      attending the CF Centre of Florence and from the hospital environment and the
      strains typed using restriction enzymes and pulsed-field gel electrophoresis
      (PFGE). Seventy (43%) of patients were colonised by P. aeruginosa, 6 (3.6%) by B.
      cepacia complex, and 11 (7%) by MRSA. Three P. aeruginosa strains were isolated
      from the sinks of the ward. All the MRSA isolates differed from each other. The
      analysis of 83 P. aeruginosa strains showed identical genotypes in five pairs of
      patients, whereas from the six patients infected with B. cepacia complex strains,
      two patients harboured identical genotypes. These pairs of patients had no
      contact with each other outside the CF centre and P. aeruginosa genotypes from
      the hospital environment differed from these clinical isolates, suggesting a
      possible common source of infection within or outside the centre. The study
      showed that, despite isolation precautions, a minimal risk of cross-infection
      still existed in the CF centre and that hygienic standards should be increased to
      further reduce this risk.

PMID- 15463903
TI  - Exopolysaccharides produced by Burkholderia cenocepacia recA lineages IIIA and
      IIIB.
AB  - Clinical and environmental strains of Burkholderia cenocepacia belonging to the
      recA lineages IIIA and IIIB were examined for exopolysaccharide (EPS) production.
      The exopolysaccharides structure was determined using mainly gas chromatography
      coupled to mass spectrometry and NMR spectroscopy. All the strains produced
      Cepacian, a highly branched polysaccharide constituted of a heptasaccharide
      repeating unit, composed of one rhamnose, one glucose, one glucuronic acid, one
      mannose and three galactose residues. This polymer is the most common
      exopolysaccharide produced by strains of the Burkholderia cepacia (Bcc) complex.
      One clinical strain produced also another polysaccharide constituted of three
      galactose units and one 3-deoxy-D-manno-2-octulosonic acid residues, a polymer
      that was previously isolated from two strains of B. cepacia genomovar I and B.
      cenocepacia IIIA.

PMID- 15463904
TI  - Immunoglobulin allotypes and IgG subclass antibody response to Aspergillus
      fumigatus in cystic fibrosis patients.
AB  - BACKGROUND: A majority of patients with cystic fibrosis (CF) become colonised
      with Aspergillus fumigatus (Af.), but only a minority develops allergic
      bronchopulmonary aspergillosis (ABPA). ABPA is associated with increased levels
      of specific immunoglobulin G (IgG) anti-Af. antibodies with a characteristic IgG
      subclass distribution. We examined whether this characteristic immune response
      was under the influence of GM and KM allotypes, which are genetic markers
      (antigenic determinants) on gamma- and kappa-light chains, respectively. METHODS:
      Sera from 233 CF patients were typed for seven GM determinants and two KM
      determinants. The types were correlated to IgG subclass anti-Af. antibody levels
      and to the presence or absence of Af. colonisation as well as ABPA. RESULTS: The
      IgG2 antibody level was significantly higher in heterozygous GM (1,2,17 23 5,21
      and 1,3,17 23 5,21) compared to homozygous GM allotypes (p = 0.02). Patients with
      the same allotypes tended to have higher IgG1 (p = 0.051). In patients with ABPA,
      being heterozygous for G1M and G3M was linked to higher IgG4 and lower IgG3 as
      compared to the other genotypes. The KM markers did not influence the antibody
      levels. The allotype GM(3 23 5), associated with atopic bronchial asthma, tended
      to make a relatively larger group in ABPA patients compared to non-ABPA and
      patients not colonised with Af. (p = 0.09). CONCLUSIONS: An influence of the GM
      allotypes on the immune response to Af. and on the development of ABPA in
      patients with CF is suggested.

PMID- 15463905
TI  - Anti-neutrophil cytoplasmatic antibodies and lung disease in cystic fibrosis.
AB  - BACKGROUND: Bactericidal-permeability-increasing protein (BPI) is a potent anti
      microbial protein produced by neutrophil granulocytes. Anti-neutrophil
      cytoplasmatic antibodies (ANCA) directed against BPI have been detected in up to
      91% in patients with cystic fibrosis (CF). We aimed to evaluate the prevalence of
      BPI-ANCA in our CF patients and to determine whether presence of BPI-ANCA is
      correlated with organ damage. METHODS: Twenty-four patients performed respiratory
      function testing and pulmonary high-resolution computed tomography (HRCT). HRCT
      was scored by using a modified Bhalla method. Serum samples were analysed by
      direct binding enzyme-linked immunosorbent assay for BPI-ANCA. RESULTS: The
      prevalence of anti-BPI-IgG was 71% and anti-BPI-IgA 33%. Twenty-nine percent of
      our patients were positive for both BPI-ANCA isotypes. Mean HRCT score was 8.0
      ranging from 0 to 22, bronchiectasis presented the most common finding (79%).
      There was a significant correlation between BPI-ANCA and both HRCT score and
      FEV(1) (p < 0.01). High levels of BPI-ANCA were correlated to chronic Pseudomonas
      aeruginosa lung infection (p < 0.01). CONCLUSIONS: BPI-ANCA was common in our
      study group. Highly significant correlations between BPI-ANCA and parameters to
      evaluate lung disease in CF may be a consequence of the inflammation process, or
      it may indicate a pathogenic role of BPI-ANCA levels in the development of lung
      disease. More research is needed and the clinical significance of our findings
      needs further evaluation.

PMID- 15463906
TI  - Cystic fibrosis at the Reunion Island (France): spectrum of mutations and
      genotype-phenotype for the Y122X mutation.
AB  - BACKGROUND: The Reunion Island is a French administrative department located in
      the Indian Ocean between the islands of Madagascar and Mauritius. Its population
      is known to be at a high risk of cystic fibrosis (CF). METHODS: Data concerning
      all CF patients born at the Reunion Island was extracted from the French CF
      Registry. Twenty-eight DeltaF508/DeltaF508, 17 Y122X/DeltaF508, and 11
      Y122X/Y122X were included in a genotype-phenotype study. RESULTS: The detection
      rate of the CFTR mutations was 83% among the CF patients born at the Reunion
      Island. Three CFTR mutations accounted for 75% of the detected CF alleles at the
      Reunion Island (DeltaF508, Y122X, and 3120 + 1G-->A.). The DeltaF508/DeltaF508,
      DeltaF508/Y122X, and Y122X/Y122X genotypes accounted for 60.2% of the CF
      patients. Patients carrying at least one Y122X mutation were pancreatic
      insufficient, had high sweat chloride values and significantly lower
      anthropometric measures. The mean anthropometric values in all three groups were
      lower that in the whole CF population followed in "continental" France. This may
      reflect the poor compliance and even the refusal of treatment noted by the
      clinicians. CONCLUSIONS: The distribution of CFTR mutations could be explained by
      the history of the Reunion Island: admixture of French settlers, African and
      Asian populations, founder effect and isolation followed by genetic drift. The
      Y122X allele appears to be associated with a severe phenotype.

PMID- 15463907
TI  - High frequency of the R75Q CFTR variation in patients with chronic obstructive
      pulmonary disease.
AB  - We performed the complete screening of the CFTR gene in a group of 31 patients
      with COPD in order to investigate the impact of mutations and polymorphisms in
      the CFTR gene. The cumulative frequency of CFTR mutations (17.74%) was
      significantly higher than in our general population (P < 0.0001). The R75Q was
      significantly overrepresented in COPD patients (8.06%; P = 0.002). In all
      patients carrying the R75Q chronic bronchitis was a dominant symptom of COPD, and
      all were homozygous for the V470 allele. These findings suggest that R75Q
      mutation could be characteristic CFTR variant for COPD patients.

PMID- 15463908
TI  - Hepatocellular carcinoma in association with cirrhosis in a patient with cystic
      fibrosis.
AB  - BACKGROUND: Cystic fibrosis liver disease (CFLD) occurs in 37% of patients with
      CF. To date and to the best of our knowledge, there has not been a documented
      case of hepatocellular carcinoma in association with cirrhosis and CF. CASE
      REPORT: A 32-year-old lady with cystic fibrosis (CF) presented for her annual
      review. She had been diagnosed with CFLD since early adolescence. A routine
      ultrasound of her liver revealed lesions consistent with hepatocellular
      carcinoma. This was confirmed on histology. She had no risk factors for
      hepatitis, and thorough investigation revealed no other cause for her chronic
      liver disease. She was also found to be pregnant at the time of diagnosis. Her
      tumour was considered too large for resection and liver transplantation and she
      was referred to a national centre for laser ablative therapy. CONCLUSION: It is
      our concern that with the increased life expectancy of patients with CF and the
      chronic nature of CFLD that this may be an increasingly recognised complication
      amongst the CF adult population. Therefore, we have changed our practice to more
      intense surveillance of patients with established CFLD to incorporate biannual
      ultrasound imaging of the hepatic system and yearly serum concentration
      measurements of alpha-fetoprotein.

PMID- 15463909
TI  - The use of cells from cystic fibrosis patients in research. A model consent form.

PMID- 15463910
TI  - Late diagnosis of cystic fibrosis in patients with bronchiectasis.

PMID- 15463911
TI  - Diagnosis of cystic fibrosis in adults with diffuse bronchiectasis.

PMID- 15463913
TI  - Birmingham welcome.

PMID- 15463912
TI  - Sweat conductivity for the diagnosis of cystic fibrosis.

PMID- 15463917
TI  - Analysis of genomic CFTR DNA.
AB  - There are numerous methodologies available for the analysis of genomic CFTR DNA.
      We present here the basic tools to allow a thorough investigation of the CFTR
      gene, beginning with the identification of potential regulatory regions using
      DNase I hypersensitive sites, and continuing with methods for the detection of
      mutations: denaturing High Performance Liquid Chromatography (dHPLC), Single
      Strand Conformation Polymorphism (SSCP), and allele-specific oligonucleotide
      (ASO) hybridisation. Also provided is a comprehensive set of PCR primers for the
      amplification of most regions of the CFTR gene. Full details of the methodologies
      given are to be found at the European Working Group on CFTR Expression website
      http://central.igc.gulbenkian.pt/cftr/vr/transcripts.html.

PMID- 15463918
TI  - Methods for RNA extraction, cDNA preparation and analysis of CFTR transcripts.
AB  - The scope of this article is to outline some of the basic methods for good
      quality RNA preparation from mammalian tissues and cells (including epithelial
      cells). Additionally, we give an outline of common techniques of measuring CFTR
      gene expression such as quantitative and semi-quantitative reverse transcription
      (RT) PCR and ribonuclease protection assay (RPA). These methods are designed to
      detect low abundance transcripts, which apply to CFTR mRNA in most cell types and
      tissues.

PMID- 15463920
TI  - Non-PCR methods for the analysis of CFTR transcripts.
AB  - Cystic fibrosis transmembrane conductance regulator gene (CFTR) shows a complex
      mechanism of tissue-specific and temporal regulation. CFTR mRNA detection and
      measurement are extremely difficult because of the low to very low levels of its
      endogenous expression. In this paper, we describe four different non-PCR methods
      optimized to analyze CFTR transcripts in epithelial cell lines, primary cell
      lines and native tissues that express significant amounts of CFTR transcript.

PMID- 15463919
TI  - Quantitative methods for the analysis of CFTR transcripts/splicing variants.
AB  - In cystic fibrosis (CF), transcript analysis and quantification are important for
      diagnosis, prognosis and also as surrogate markers for some therapies including
      gene therapy. Classical RNA-based methods require significant expression levels
      in target samples for appropriate analysis, thus PCR-based methods are evolving
      towards reliable quantification. Various protocols for the quantitative analysis
      of CFTR transcripts (including those resulting from splicing variants) are
      described and discussed here.

PMID- 15463921
TI  - Microarray analysis in cystic fibrosis.
AB  - DNA microarrays provide a versatile platform for applications including gene
      expression analysis and genotyping. In the case of cystic fibrosis (CF), DNA
      microarrays enable the measurement of gene expression levels of thousands of
      genes in parallel, and potentially therefore, to identify non-CFTR genes down- or
      up-regulated in CF, which could lead to insights into disease pathophysiology, as
      well as novel molecular markers and therapeutic strategies. Moreover, using
      optimised microarray protocols based on either primer extension analysis (i.e.
      minisequencing) or electronic hybridisation stringency control, the potential now
      exists to detect all relevant CFTR mutations on a single DNA microarray as a
      novel platform for CF screening.

PMID- 15463923
TI  - Immunohistochemistry of CFTR in native tissues and primary epithelial cell
      cultures.
AB  - Studies on CFTR protein expression and localization in native tissues or in
      primary cultures of human epithelial cells are scarce due to the intrinsic
      instability of this protein, its low expression in most tissues and also to
      technical difficulties. However, such data are of the highest importance to
      understand the pathophysiology of CF. The purpose of this article is to outline
      several assays for the characterization of primary epithelial cultures and to
      review different CFTR immunostaining protocols.

PMID- 15463924
TI  - Assessment of CFTR localisation in native airway epithelial cells obtained by
      nasal brushing.
AB  - Reliable methods for determining the localisation of mutant CFTR protein in
      native cells from CF individuals are necessary to allow the degree of
      mislocalisation of any genotype to be defined and to assess the effect of
      therapeutic agents on CFTR trafficking. Here, we present procedures for obtaining
      ciliated epithelial cells from CF patients by nasal brushing and a description of
      protocols for immunolocalisation of CFTR. The protocols are a consensus,
      following comparison of some aspects of methods currently used in the authors'
      laboratories.

PMID- 15463925
TI  - Isolation and air-liquid interface culture of human large airway and bronchiolar
      epithelial cells.
AB  - This article describes the techniques of isolation and culture of human airway
      epithelial cells from large airways and from distal airways. Both cell types are
      obtained from lung pieces collected during surgery. The protocols start with an
      initial step of washing and dissection of the lung pieces to separate large
      airways or distal airways from the surrounding parenchyma. The second step is
      enzymatic isolation of epithelial cells from the dissected large or distal
      airways. Cells are then collected by centrifugation and then seeded onto collagen
      surfaces. Epithelial cells can be grown at an air-liquid interface and usually
      form a confluent and functional epithelial layer within days.

PMID- 15463926
TI  - Sequential monolayer-suspension culture of human airway epithelial cells.
AB  - In this article, we describe a technique for culturing human airway epithelial
      cells, developed in Leuven, as a new tool for a most reliable diagnosis for
      ciliary disorders. This technique that allows to keep both structural and
      functional primary abnormalities of inherited ciliary abnormalities, while
      avoiding the secondary ones, can also be useful to a number of other studies,
      namely in cystic fibrosis.

PMID- 15463927
TI  - Three-dimensional human airway epithelial cell cultures.
AB  - An epithelial airway-derived 3-D cell culture model is described. The long
      lifetime of this model, compared to monolayer cultures of primary cells, allows
      many experiments with material from one single patient to be performed.

PMID- 15463929
TI  - Reconstitution of human airway tissue in the humanized xenograft model.
AB  - Normal human airway epithelial tissue may be reconstituted in the humanized
      xenograft model in immunodeficient NUDE mice. Epithelial cells dissociated from
      human fetal or adult tissue are seeded on a denuded rat trachea and implanted in
      the NUDE mice. After a first step of dedifferentiation, the human epithelial
      cells adhere on the denuded basal lamina of the rat host trachea and
      progressively reconstitute a normal well-differentiated epithelium after several
      steps of migration, proliferation, stratification and redifferentiation.

PMID- 15463928
TI  - Murine epithelial cells: isolation and culture.
AB  - We describe an air-liquid interface primary culture method for murine tracheal
      epithelial cells on semi-permeable membranes, forming polarized epithelia with a
      high transepithelial resistance, differentiation to ciliated and secretory cells,
      and physiologically appropriate expression of key genes and ion channels. We also
      describe the isolation of primary murine nasal epithelial cells for patch-clamp
      analysis, generating polarised cells with physiologically appropriate
      distribution and ion channel expression. These methods enable more
      physiologically relevant analysis of murine airway epithelial cells in vitro and
      ex vivo, better utilisation of transgenic mouse models of human pulmonary
      diseases, and have been approved by the European Working Group on CFTR
      expression.

PMID- 15463931
TI  - Antibodies for CFTR studies.
AB  - For most expression studies focusing on the Cystic Fibrosis Transmembrane
      Conductance Regulator (CFTR) protein, sensitive and specific antibodies (Abs) are
      critically needed. Several Abs have been produced commercially or by research
      laboratories for CFTR detection in both cell lines with heterologous or
      endogenous expression and native cells/tissues. Here, we review the applicability
      of most Abs currently in use in CF research for the biochemical and/or
      immunocytochemical detection of CFTR.

PMID- 15463932
TI  - Biochemical methods to assess CFTR expression and membrane localization.
AB  - Detection of cystic fibrosis transmembrane conductance regulator (CFTR) protein
      is usually a difficult task to accomplish due to the low levels of expression and
      high turnover that this membrane protein is submitted to in the cell. Common
      biochemical methods can be used for the detection of CFTR but several critical
      points must be taken into account. The scope of this article is to outline
      biochemical methods commonly used to assess CFTR expression, processing and
      membrane localization.

PMID- 15463933
TI  - Methods to study CFTR protein in vitro.
AB  - CFTR is a cyclic AMP and nucleotide-related chloride-selective channel with a low
      unitary conductance. Many of the physiological roles of CFTR are effectively
      studied in intact cells and tissues. However, there are also several clear
      advantages to the application of cell-free technologies to the study of the
      biochemical and biophysical properties of CFTR. When expressed in heterologous
      cells, CFTR is processed relatively poorly, depending, however, on the cell-type
      analysed. In some cells, only 20-25% of the protein which is initially
      synthesized exits the endoplasmic reticulum to insert into the cell membrane
      [Cell 83 (1995) 121; EMBO J. 13 (1994) 6076]. Further, many of the disease
      causing mutants of CFTR result in even lower processing efficiencies. Therefore,
      several procedures have been developed to study regulated CFTR channel function
      expressed in microsomal membranes and following its purification and
      reconstitution. These experimental approaches and their application are discussed
      here.

PMID- 15463934
TI  - Proteomics techniques for cystic fibrosis research.
AB  - Numerous factors, other than mutations in the CFTR gene, affect the phenotypic
      variability of cystic fibrosis (CF). With a two-dimensional electrophoresis (2
      DE) analysis of total protein expression profiles (proteomics) of CF versus non
      CF cells it is possible to obtain an integrative picture of CF cellular
      alterations. Through this approach, proteins that interact differently with wild
      type- and mutant-CFTR can also be identified (interactomics). This can provide
      insight into CF pathophysiology as well as clues for novel therapeutic targets.
      Additionally, protein profiling can ultimately identify novel disease markers
      with the potential for a CF diagnosis not based on the analysis of CFTR gene.

PMID- 15463935
TI  - Cystic fibrosis: recent structural insights.
AB  - Cystic fibrosis (CF) is a debilitating human disease caused by mutations in the
      cystic fibrosis transmembrane conductance regulator (CFTR) gene. The recently
      solved crystal structures of the murine CFTR nucleotide binding domain (NBD)
      provide insight into the molecular basis of several CF-causing mutations. In
      addition, the NBD structures reveal several unexpected findings that may have
      implications concerning CFTR function. In this mini-review, we discuss the key
      structural features of ATP Binding Cassette (ABC) transporter NBDs, as well as
      highlight how structural information has aided our understanding of the ATP
      regulated solute transport cycle.

PMID- 15463936
TI  - Altered terminal glycosylation and the pathophysiology of CF lung disease.
AB  - Altered terminal glycosylation, with increased fucosylation and decreased
      sialylation, is a hallmark of the cystic fibrosis (CF) glycosylation phenotype.
      The glycosylation phenotype of CF airway epithelial cells has been modulated by
      the expression of wtCFTR. Understanding the effects of mutant CFTR on
      glycosylation may provide further insight into the regulation of glycoconjugate
      processing as well as new approaches to the therapy of CF.

PMID- 15463937
TI  - Methods for the study of lipid metabolites in cystic fibrosis.
AB  - Lipid studies in the context of cystic fibrosis have been addressed from two
      perspectives: the analysis of lipid metabolites in a given tissue at a particular
      time point, and the metabolic studies that involve tracing of specific molecules.
      This review summarizes the methods used to date.

PMID- 15463939
TI  - The patch-clamp and planar lipid bilayer techniques: powerful and versatile tools
      to investigate the CFTR Cl- channel.
AB  - Using the patch-clamp (PC) and planar lipid bilayer (PLB) techniques the
      molecular behaviour of the cystic fibrosis transmembrane conductance regulator
      (CFTR) Cl- channel can be visualised in real-time. The PC technique is a highly
      powerful and versatile method to investigate CFTR's mechanism of action,
      interaction with other proteins and physiological role. Using the PLB technique,
      the structure and function of CFTR can be investigated free from the influence of
      other proteins. Here we discuss how these techniques are employed to investigate
      the CFTR Cl- channel with special emphasis on its permeation, conduction and
      gating properties.

PMID- 15463940
TI  - CFTR, investigated with the two-electrode voltage-clamp technique: the importance
      of knowing the series resistance.
AB  - When the gene mutated in cystic fibrosis (CF) was identified and named the cystic
      fibrosis transmembrane conductance regulator (CFTR), it was not immediately clear
      what its function might be. Subsequent analysis showed that it is an anion
      channel, but also other functions were proposed. This protocol aims to shortly
      describe the two-electrode voltage-clamp (TEVC) technique and to highlight some
      precautions when studying CFTR with it. A short description of the series
      resistance (RS) and its influence on measurements of channel characteristics is
      given.

PMID- 15463941
TI  - Microelectrodes and their use to assess ion channel function.
AB  - Impalement of living cells with microelectrodes (MEs) is a useful approach to
      measure a variety of biological parameters such as membrane potential (Vm),
      intracellular free ion concentrations and cell-to-cell communication. Despite
      such widespread applications, the number of trained researchers capable of using
      MEs is diminishing. In this article, we describe the fundamentals of the
      preparation and the proper use of MEs to study the physiology of transepithelial
      ion transport.

PMID- 15463942
TI  - Determination of CFTR chloride channel activity and pharmacology using
      radiotracer flux methods.
AB  - Flux studies using either radioisotopes or ion-selective electrodes are a
      convenient method to assay the function of the cystic fibrosis transmembrane
      conductance regulator (CFTR) Cl- channel. Here, we described three different
      protocols to study the properties, regulation and pharmacology of the CFTR Cl-
      channel in populations of cells and artificial vesicles. These techniques are
      widely used to evaluate the function of wild-type and mutant CFTR prior to
      detailed analyses using the patch-clamp technique. Moreover, they have proved
      especially valuable in the search for new drugs to treat cystic fibrosis.

PMID- 15463943
TI  - Transepithelial electrical measurements with the Ussing chamber.
AB  - The Ussing chamber technique is a simple, but powerful technique to investigate
      ion transport. Originally designed to study vectorial ion transport through the
      frog skin, it has revolutionized our knowledge about how eletrolytes permeate
      epithelia. Here we discuss the physiological principles that underlie the
      technique and protocols to investigate the role of the cystic fibrosis
      transmembrane conductance regulator (CFTR) in transepithelial ion transport.

PMID- 15463944
TI  - Transepithelial fluctuation analysis of chloride secretion.
AB  - Transepithelial fluctuation analysis (noise analysis) provides valuable
      information about the density and single-channel properties of ion channels in
      intact epithelia. Here we investigate cystic fibrosis transmembrane conductance
      regulator (CFTR)-dependent chloride (Cl-) secretion in T84 human colonic
      epithelia by inducing noise using the diarylsulfonylurea DASU-01, a low-affinity
      open-channel blocker of CFTR. Our data indicate that the apical membrane of
      maximally stimulated T84 epithelia has a very high Cl- conductance generated by
      approximately 7000 active CFTR channels per cell with open probability (Po) of
      approximately 0.4 and single-channel amplitude (i) of approximately 0.1 pA.
      Similar experiments might provide important information about how drugs regulate
      CFTR in intact epithelia.

PMID- 15463945
TI  - ATPase assay of purified, reconstituted CFTR protein.
AB  - The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a
      phosphorylation and nucleotide regulated chloride channel. CFTR also directly
      mediates the hydrolysis of ATP and this catalytic activity is loosely coupled to
      CFTR channel gating. However, mechanistic detail regarding the role of ATP
      hydrolysis in channel function is lacking. Our further understanding of the
      molecular basis for normal channel activity requires kinetic analysis of the
      ATPase activity by the full-length protein. This article describes an effective
      assay of ATPase activity by purified, reconstituted CFTR protein.

PMID- 15463946
TI  - Measurements of airway surface liquid height and mucus transport by fluorescence
      microscopy, and of ion composition by X-ray microanalysis.
AB  - The respiratory tract is lined by a thin layer of fluid, the airway surface
      liquid (ASL), which plays a critical role in lung defense. The paper describes
      methods to determine the height of the ASL and corresponding mucus transport
      rates using fluorescent probes, and methods to determine the ionic composition of
      the ASL by X-ray microanalysis.

PMID- 15463947
TI  - Strategies to investigate the mechanism of action of CFTR modulators.
AB  - The malfunction of the cystic fibrosis transmembrane conductance regulator (CFTR)
      Cl- channel is associated with a wide spectrum of disease. In the search for
      modulators of CFTR, pharmaceutical agents have been identified that (i) act
      indirectly by regulating the protein kinases and phosphatases, which control
      CFTR, and (ii) interact directly with CFTR. Some agents modulate CFTR by altering
      the function of the nucleotide-binding domains (NBDs) that control channel
      gating, whereas others inhibit CFTR by preventing Cl- flow through the channel
      pore. Knowledge of CFTR modulators might lead to new understanding of the CFTR Cl
      channel, its physiological role and malfunction in disease.

PMID- 15463948
TI  - In-vivo and ex-vivo functional assessment.

PMID- 15463950
TI  - Intestinal current measurements to diagnose cystic fibrosis.
AB  - Electrophysiological techniques are essential for the diagnosis of cystic
      fibrosis. In the past ten years intestinal current measurements has emerged as
      valuable tool for this purpose. This overview highlights the objectives,
      methodology and current protocols to diagnose cystic fibrosis by intestinal
      current measurement on rectal biopsies.

PMID- 15463949
TI  - Basic protocol for transepithelial nasal potential difference measurements.
AB  - Transepithelial nasal potential difference (NPD) measurements assess ion
      conductance in the upper respiratory epithelium. NPD is useful in assisting in
      the diagnosis of classical and atypical cystic fibrosis (CF) and of cystic
      fibrosis transmembrane regulator (CFTR)-related disorders, as well as for
      monitoring the effect of pharmacological agents and gene transfer approaches to
      correct the abnormalities of ion transport in CF. The article summarizes the
      objectives and the principle of NPD measurements, describes a hands-on protocol
      of the procedure and provides quality control measures, practical hints and
      troubleshooting.

PMID- 15463951
TI  - Ex vivo CF diagnosis by intestinal current measurements (ICM) in small aperture,
      circulating Ussing chambers.
AB  - Intestinal current measurements (ICM) on rectal suction biopsies are a tool for
      the ex vivo diagnosis of classical and atypical cystic fibrosis (CF). We present
      the basic ICM protocol, typical tracings and their interpretation. The ICM
      technique allows the registration of CF-induced changes in electrogenic
      transepithelial ion transport (Cl-, HCO3-, K+) in a Cl- secretory epithelium, and
      on the basis of pharmacological criteria, is able to discriminate between CFTR
      mediated Cl- secretion and secretion through alternative anion channels. ICM is
      particularly useful for the classification of individuals with CF-like clinical
      features with equivocal sweat test values and/or no or one identifiable CFTR
      mutation.

PMID- 15463952
TI  - Assessment of CFTR function in rectal biopsies for the diagnosis of cystic
      fibrosis.
AB  - The Ussing chamber technique has contributed significantly to our understanding
      of the role of ion transport in the pathogenesis of human diseases like cystic
      fibrosis (CF). Here, we summarize protocols developed to study the Cl- channel
      function of the cystic fibrosis transmembrane conductance regulator (CFTR)
      protein in rectal biopsies from normal individuals and CF patients. These
      protocols can be applied to study the function and pharmacological modulation of
      wild-type and mutant CFTR in the context of the native epithelium. Together with
      sweat testing and genetic analyses, these functional measurements may aid in
      establishing a diagnosis of CF.

PMID- 15463953
TI  - Measurement of halide efflux from cultured and primary airway epithelial cells
      using fluorescence indicators.
AB  - The use of the halide-sensitive fluorescent probes (6-methoxy-N-(
      sulphopropyl)quinolinium (SPQ) and N-(ethoxycarbonylmethyl)-6-methoxyquinolinium
      bromide (MQAE)) to measure chloride transport in cells has now been established
      as an alternative to the halide-selective electrode technique, radioisotope
      efflux assays and patch-clamp electrophysiology. We report here procedures for
      the assessment of halide efflux, using SPQ/MQAE halide-sensitive fluorescent
      indicators, from both adherent cultured epithelial cells and freshly obtained
      primary human airway epithelial cells. The procedure describes the calculation of
      efflux rate constants using experimentally derived SPQ/MQAE fluorescence
      intensities and empirically derived Stern-Volmer calibration constants. These
      fluorescence methods permit the quantitative analysis of CFTR function.

PMID- 15463954
TI  - Measurement of chloride transport in nasal epithelial cells by X-ray
      microanalysis.
AB  - Nasal epithelial cells are a representative and easy to obtain system of
      epithelial cells for the study of chloride transport. X-ray microanalysis (XRMA)
      allows the direct and simultaneous measurement of several elements of biological
      interest, including chloride. Here, a method is presented for the preparation of
      nasal epithelial cells for X-ray microanalysis and for the determination of
      chloride transport by this analytical technique.

PMID- 15463956
TI  - Animal models of cystic fibrosis.
AB  - Animal models of cystic fibrosis, in particular several different mutant mouse
      strains obtained by homologous recombination, have contributed considerably to
      our understanding of CF pathology. In this review, we describe and compare the
      main phenotypic features of these models. Recent and possible future developments
      in this field are discussed.

PMID- 15463957
TI  - Established cell lines used in cystic fibrosis research.
AB  - The development of immortalized cell lines has been a significant benefit to the
      study of human disease, due to limitations in using primary cells and the
      availability of tissue. The immortalization of cells from cystic fibrosis (CF)
      patients as well as cells from non-CF individuals from tissues relevant to CF has
      been critical to enhancing our understanding of the physiological, biochemical
      and genetic mechanisms underlying CF and for the development of therapeutic
      strategies designed to manage CF pathology. A comprehensive list of immortalized
      cells from various tissue and species, with an emphasis on epithelial cells, is
      presented and discussed here.

PMID- 15463958
TI  - Airway epithelial cell-pathogen interactions.
AB  - Cystic fibrosis (CF) airway becomes colonized with only a limited number of
      bacterial pathogens. It is of paramount importance to establish in vitro and in
      vivo models to better understand bacterial-host interactions under CF-like
      conditions. In this article, in vitro methods suitable to study Pseudomonas
      aeruginosa (Pa) and Staphylococcus aureus (Sa) adherence to and uptake by airway
      epithelial cells are described. Acute and chronic respiratory infection models,
      which have been used in CF transgenic mice and mimic human CF lung pathology, are
      also taken into consideration.

PMID- 15463959
TI  - Gene delivery systems--gene therapy vectors for cystic fibrosis.
AB  - Gene delivery systems (GDS) play a central role in the development of gene
      therapy strategies for Cystic Fibrosis (CF). Further, these systems are important
      tools in studies with cultured cells and in animal models. In this review, we
      describe the properties of several viral and synthetic gene delivery systems, and
      evaluate their possible application in gene therapy of CF. While many gene
      delivery systems give satisfactory results in cultured or animal studies, none of
      these systems has been shown to fulfil all the requirements of safety and
      efficacy for use in CF patients. The intact airway epithelium, the most important
      target in CF gene therapy, proves to be well protected against invading vector
      systems.

PMID- 15463961
TI  - Autarchy, market disintegration, and health: the mortality and nutritional crisis
      in Nazi Germany, 1933-1937.
AB  - Trends in mortality, nutritional status and food supply are compared to other
      living standard indicators for the Weimar Republic (1919-1933) and for the early
      years of the Nazi regime (1933-1937). The results imply that Germany experienced
      a substantial increase in mortality rates in most age groups in the mid-1930s,
      even relative to those of 1932, the worst year of the Great Depression. Moreover,
      children's heights--an indicator of the quality of nutrition and health--were
      generally stagnating between 1933 and 1938, but had increased significantly
      during the 1920s. Persecution, by itself, does not explain such an adverse
      development in biological welfare; the non-persecuted segments of the German
      population were affected as well. The reason for this adverse development was
      caused by the fact that military expenditures increased at the expense of public
      health measures. In addition, food imports were curtailed, and prices of many
      agricultural products were controlled. There is ample evidence that this set of
      economic policies had an adverse effect on the health and nutritional status of
      the population. The highly developed areas of Germany with large urban sectors
      and the coastal regions of the Northwest were affected most from the policy of
      restricting imports of protein-rich agricultural products.

PMID- 15463962
TI  - Physical growth in a transitional economy: the aftermath of South African
      apartheid.
AB  - The economic transition in developing countries is not always the result of the
      change from a centrally-planned to a free-market economy, but may be found within
      an already existing free-market economy as a result of profound political change,
      as in South Africa. The release of Nelson Mandela in February 1990 heralded an
      end both to the political system of apartheid and to the concomitant social,
      political, and economic disenfranchisement of 30 million non-White people in
      South Africa. The first freely elected non-White government came to power in 1994
      and initiated a number of social and economic reforms aimed at alleviating the
      worst consequences of apartheid. This paper examines the effect of post-apartheid
      economic and social transition on the growth and development of urban children.
      Over 4000 children born in Soweto and Johannesburg were enrolled in the Birth to
      Ten (BTT) birth-cohort study in 1990. Whilst these children were born with lower
      birth weights than in developed countries, they did grow strongly in infancy,
      particularly in weight, to reflect normal reference values for body mass index
      (BMI) by 1 year of age. While post-apartheid social and economic changes were
      expected to take some time to affect child growth and development, the rate of
      change has been slower than expected. Data from the BTT study demonstrate that
      the growth of White children continues to be superior to that of their non-White
      peers and differences that existed at birth and during infancy have not
      diminished during childhood and early adolescence. Whatever factors are changed
      at the national or community levels during economic (and social) transition in
      South Africa appear not yet to have resulted in improved child physical growth.

PMID- 15463963
TI  - Anthropometric status of Kazakh children in the 1990s.
AB  - The 1990s were a period of considerable economic and social instability in
      Kazakhstan. The current study documents information on the growth performance of
      children living in Kazalinsk district in the far west of Kazakhstan over this
      turbulent period. Using anthropometric data of children, from random samples
      collected in 1992, 1994 and 2000, we investigate changes in body size of 4.0-4.9
      year-old children over the 8-year-study period. Between 1992 and 2000, there was
      no statistically significant change in body size of 4.0-4.9-year-old boys, but
      4.0-4.9-year-old girls became significantly smaller. This may have resulted from
      the prolonged period of economic instability in Kazakhstan. Furthermore, using
      detailed dietary intake data collected in 1994, evidence is presented to support
      a suggestion that the different responses to economic hardship, evidenced in the
      achieved body size of boys and girls, may have been influenced by gender
      discrimination in household food allocation.

PMID- 15463964
TI  - Socio-economic determinants of health and physical fitness in southern Ethiopia.
AB  - The dependence of health and physical fitness on the socio-economic factors of
      rural families in southern Ethiopia is investigated, with particular emphasis on
      the role of inequality. This paper contributes to our knowledge of the effect of
      inequality on health in several ways: it compares the results of objective and
      subjective health measures, it distinguishes between wealth inequality and
      nutrition inequality, and it evaluates the impact of nutrition inequality both at
      the village level and at the household level. The subjective health measures are
      the number of days respondents were ill during the last month, their ability to
      walk distances, their ability to carry heavy loads, and their ability to work in
      the field. The objective health measure is having Body Mass Index (BMI) lower
      than 18.5. Males are healthier than females. Height has a positive and
      significant effect on health and fitness and the same is true for per-capita
      wealth measured at the village level. Availability of satisfactory health
      facilities has a negative effect on morbidity. Per-capita wealth inequality is
      positively associated with morbidity and with a low BMI. Within-household
      nutrition inequality has a complex effect on health and physical fitness: the
      effect is negative, but only for household members whose nutritional status is
      above the household mean. The results indicate a clear positive effect of
      economic well-being on health and physical fitness. The role of inequality is
      less clear, and certainly deserves further analyses at both the theoretical and
      empirical levels.

PMID- 15463965
TI  - Non-parametric regression with BayesX: a flexible estimation of trends in human
      physical stature in 19th century America.
AB  - The recently developed computer program BayesX provides a Bayesian approach to
      the estimation of non-parametric additive models. Such models can be useful in
      applications when the effect of metrical covariates (such as time) are to be
      estimated while controlling for other factors. In an application of this
      methodology, trends in the height of West Point cadets in the 19th century are
      estimated. The results indicate that the biological standard of living of the
      "middle class" increased relative to the rest of the American society during the
      Antebellum years.

PMID- 15463966
TI  - Does bone mineralization reflect economic conditions? An examination using a
      national US sample.
AB  - BACKGROUND: Bone density is the most important determinant of osteoporotic
      fractures, which lead to significant morbidity, disability and mortality for
      older persons, particularly women. Sensitive periods for bone mineralization in
      infancy, childhood and adolescence overlap with those for height attainment.
      After peak density is reached in early adulthood, there is age-related decline.
      We ask whether bone density, as height, reflects economic conditions. SUBJECTS
      AND METHODS: Using the third National Health and Nutrition Examination Survey, a
      probability sample of the US population which over-sampled Blacks and Mexican
      Americans, we examine the associations between adult bone mineral content (BMC)
      adjusted for bone and body size and three economic indicators: education, height
      and the poverty income ratio (PIR). We compare four groups: US-born Whites,
      Blacks and Mexican Americans and Mexican-born Mexican Americans. RESULTS:
      Education is positively associated with BMC only for White women, although there
      are similar, non-significant associations for Black women and White and Black
      men. For women, BMC is more strongly associated with height for Mexican
      Americans, especially the Mexican-born, than for Whites. For men, the only
      significant association is a negative one with education for men born in Mexico.
      PIR is not significantly associated with BMC, although there is pattern of lower
      income being associated with lower BMC for Whites and Blacks and higher BMC for
      Mexican Americans. CONCLUSION: Bone density does not reflect economic conditions
      as strongly or consistently as does physical stature. However, for women there is
      evidence that lower economic status in childhood or adolescence is associated
      with lower bone density.

PMID- 15463967
TI  - The hidden penalties of gender inequality: fetal origins of ill-health.
AB  - This paper is concerned with the interconnections between gender inequality and
      maternal deprivation, on the one hand, and the health of children (of either sex)
      and of adults that the children grow into (again, of either sex). The basic
      message of the paper is that women's deprivation in terms of nutrition and
      healthcare rebounds on the society as a whole in the form of ill-health of their
      offspring-males and females alike-both as children and as adults. There are a
      variety of pathways through which women's deprivation can affect the health of
      the society as a whole. This paper focuses on the pathways that operate through
      undernourishment of the mother. Maternal deprivation adversely affects the health
      of the fetus, which in turn leads to long-term health risks that extend not just
      into childhood but into adulthood as well. There are, however, important
      differences in the way children and adults experience the consequences of
      maternal deprivation via fetal deprivation. In particular, the pathways that lead
      to their respective risk factors and the circumstances under which those risk
      factors actually translate into ill-health are very different. These differences
      are best understood through the concept of 'overlapping health transition' in
      which two different regimes of diseases coexist side by side. Gender inequality
      exacerbates the old regime of diseases among the less affluent through the
      pathway of childhood undernutrition. At the same time it also exacerbates the new
      regime of diseases among the relatively more affluent through a pathway that has
      come to be known as the 'Barker hypothesis'. Gender inequality thus leads to a
      double jeopardy-simultaneously aggravating both regimes of diseases and thus
      raising the economic cost of overlapping health transition.

PMID- 15463968
TI  - Trends in body size, diet and food availability in the Cook Islands in the second
      half of the 20th century.
AB  - The body size of adult Cook Islanders on Rarotonga for the years 1952, 1966 and
      1996 has been increasing. The rate of increase in stature of women aged 20-39
      years was 0.5cm per decade across the period 1952-1966, and 0.8cm per decade for
      the period 1966-1996. The rate of increase of weight in the 20-29 years age group
      was 0.6kg per decade in period 1, and 7.3kg per decade in period 2. In the age
      group 30-39 years, the rates were 3.2kg per decade and 5.1kg per decade
      respectively. Changing food availability for the period 1961-2000 is used to
      compare estimates of dietary energy availability with estimates of physiological
      energy requirements. There has been reduced availability of traditional staples,
      a likely reduction in consumption of fish, increased consumption of meat, and a
      decline in the availability of dietary fats and oils. Daily per capita energy
      intakes in 1952 and 1966 greatly exceed an hypothetical physiological maximum
      value for energy expenditure, suggesting a large positive energy balance in 1952
      and an even greater one in 1966, both predisposing to weight gain. Although daily
      per capita energy availability in 1996 is similar to the hypothetical
      physiological maximum value for energy expenditure, it exceeds the measured level
      of energy expenditure at that time. It is speculated that excessive energy intake
      relative to requirement is more likely to predispose to positive energy balance
      and weight gain than decline in energy expenditure, although to a lower extent
      than in 1966 and 1952.

PMID- 15463969
TI  - A history of health in Europe from the late Paleolithic era to the present.
AB  - This article briefly describes a large, multidisciplinary research project that
      combines skeletal data in Europe over the past 10,000 years with information from
      sources in history, archaeology, geography and climate history to measure and
      analyze important aspects of human health. Over this era human health was
      significantly affected by climate change, the rise of settled agriculture,
      urbanization, new technologies, global exploration and colonization, and
      industrialization.

PMID- 15463970
TI  - Economic and anthropological assessments of the health of children in Maya
      immigrant families in the US.
AB  - Immigration from developing countries to the US generally increases access to
      health care and clean water, but it also introduces some unhealthy lifestyle
      patterns, such as diets dense in energy and little regular physical activity. We
      present a transdisciplinary model of child health and examine the impact of
      immigration on the physical growth and health of Maya children in Guatemala and
      the US. Maya-American children are much taller and have longer legs, on average,
      than their counterparts in Guatemala. This suggests that immigration to the US
      improves their health. However, the Maya-American children also are much heavier
      than both Guatemalan Maya and White American children, and have high rates of
      overweight and obesity. Quantile regression analysis indicates that Maya are
      shorter except in the upper tail of the stature distribution, and have higher
      Body Mass Index (BMI) in the tails, but not in the middle of the BMI
      distribution. Leisure time spent in front of a television or computer monitor
      tends to raise BMI in the middle and lower tail of the distribution, but not in
      the upper tail.

PMID- 15463971
TI  - The secular trend in human physical growth: a biological view.
AB  - Nutritionists and anthropometric historians alike are familiar with the secular
      trend-height and weight in adults, and the rate of physical development in
      children, increasing since at least the mid 19th century. The social conditions
      which drive this trend are of interest to anthropometric historians, but the
      underlying biology is also important. Here the trends for height, weight and
      menarcheal age are summarised and contrasted. In Northern Europe, adult height
      has largely stabilised, and the age of menarche has also settled at around 13
      years, while weight continues to increase due to obesity. The increase in height
      from one generation to the next occurs mainly in the first 2 years of life, due
      to increases in leg length. The height trend has lasted for 150 years or more,
      i.e. for six generations, because the rate of catch-up from one generation to the
      next is biologically constrained to avoid the cost of too rapid catch-up.

PMID- 15463972
TI  - The ups and downs of Mexican economic growth: the biological standard of living
      and inequality, 1870-1950.
AB  - The secular change in the biological standard of living of the Mexican population
      between 1870 and 1950 is examined based on evidence on the physical stature from
      military and passport records. While Mexico industrialized and experienced rapid
      economic growth during this period, there was only a modest overall improvement
      in the height, health and nutritional status of the Mexican population. The
      average Mexican born in the 1940s was not only slightly taller than its
      compatriot of the 1870s. There were, however, considerable social differences:
      the Mexican upper class was markedly taller than the working class and the gap
      increased prior to the revolution. Economic growth with systemic inequality
      largely accounts for such a pattern.

PMID- 15463973
TI  - The biological standard of living in Taiwan under Japanese occupation.
AB  - This paper presents evidence on the biological standard of living in Taiwan from
      1842 to 1931 using Taiwanese height and weight data collected by the Japanese
      authorities from 1921 to 1931. This study shows that in the late Ch'ing adult
      heights were not increasing over time, while the adult heights of those born
      after the Japanese takeover did begin to increase rapidly. Evidence from
      children's heights confirms that this growth in height continued through the
      1920s. The body mass index of Taiwanese, however, did not increase in the 1920s.
      By most measures, the biological standard of living was better in the north of
      the island. Comparison with modern data shows that heights have continued to
      increase.

PMID- 15463974
TI  - Human capital, schooling and health.
AB  - A consensus has been forged in the last decade that recent periods of sustained
      growth in total factor productivity and reduced poverty are closely associated
      with improvements in a population's child nutrition, adult health, and schooling,
      particularly in low-income countries. Estimates of the productive returns from
      these three forms of human capital investment are nonetheless qualified by a
      number of limitations in our data and analytical methods. This paper reviews the
      problems that occupy researchers in this field and summarizes accumulating
      evidence of empirical regularities. Social experiments must be designed to assess
      how randomized policy interventions motivate families and individuals to invest
      in human capital, and then measure the changed wage opportunities of those who
      have been induced to make these investments. Statistical estimation of wage
      functions that seek to represent the relationship between wage rates and a
      variety of human capital stocks may yield biased estimates of private rates of
      return from these investments for a variety of reasons. The paper summarizes
      several of these problems and illustrates how data and statistical methods can be
      used to deal with some of them. The measures of labor productivity and the
      proxies specified for schooling and adult health are first discussed, and then
      the functional relationships between human capital and wages are described. Three
      types of estimation problem are discussed: (1) bias due to omitted variables,
      such as ability or frailty; (2) bias due to the measurement of an aggregation of
      multiple sources of human capital, e.g. genetic and socially reproducible
      variation, which may contribute to different gains in worker productivity; and
      (3) errors in measurement of the human capital stocks. Empirical examples and
      illustrative estimates are surveyed.

PMID- 15463975
TI  - Epidemiological transitions, reproductive health, and the Flexible Response
      Model.
AB  - In concert with improving standards of living since the mid-19th century, chronic
      and non-infectious diseases replaced infectious diseases as the major causes of
      mortality in more developed countries. Thus, economic development has been seen
      as one strategy to improve women's reproductive health. However, rates of two of
      the major contributors to women's illness, maternal mortality and breast cancer,
      do not correspond well with the level of economic development. Drawing upon our
      longitudinal study of reproductive functioning among rural Bolivians (Project
      Reproduction and Ecology in Provincia Aroma (REPA)), we propose an evolutionary
      model to explain variation in certain aspects of women's reproductive health. Our
      findings suggest new avenues of inquiry into the determinants of reproductive
      health and have implications for improving the well-being of women worldwide.

PMID- 15463976
TI  - Height cycles in the 18th and 19th centuries.
AB  - Spectral analysis of the physical stature of Americans and Europeans in the 18th
      and 19th centuries reveals a cyclical structure similar to the traditional view
      of the business cycle: a longer cycle with a length of 7-10 years, and a shorter
      cycle with a length of 3-5 years. The correlation between height cycles and
      cycles of economic variables such as grain prices indicates an influence of
      economic cycles on physical stature. The phase shift between the cycles indicates
      that economic conditions are especially important for growth in infancy. In part,
      this result is due to a cumulative effect: born into a recessionary period, a
      child is likely to face several cyclical downturns during the growing years.

PMID- 15463977
TI  - The effect of new drug approvals on HIV mortality in the US, 1987-1998.
AB  - After increasing steadily from 1987 to 1995, the number of US deaths caused by
      human immunodeficiency virus (HIV) declined sharply from 1995 to 1998. We analyse
      aggregate data to consider the hypothesis that this decline was due to a rapid
      increase in the number of drugs available to treat HIV. The evidence suggests
      that new drugs played a key role in the post-1995 decline in HIV mortality. The
      annual number of HIV deaths is estimated to have been reduced by over 6000, on
      average, by an additional HIV drug approval. The social return to HIV drug
      innovation appears to be extremely large.

PMID- 15463978
TI  - The making of giants in a welfare state: the Norwegian experience in the 20th
      century.
AB  - The population of Norway has become one of the tallest in the world even
      overtaking Americans during the course of the second half of the 20th century-not
      in terms of income, but in terms of physical stature and other indicators of
      biological welfare, such as longevity. This is also the case in several other
      west-European welfare states. Both income and physical stature have converged
      across Norwegian counties since the 1930s. We formulate the hypothesis that the
      west-European and Scandinavian welfare states perform well in mitigating spatial
      inequality in well being, in the sense that they translate income quite
      effectively into the biological well being of the population as a whole.

PMID- 15463980
TI  - Heights, calories and welfare: a new perspective on Italian industrialization,
      1854-1913.
AB  - The height of Italian conscripts was increasing throughout the second half of the
      19th century due primarily to an increases in food intake, but also to an
      improvement in sanitary conditions, and diffusion of primary schooling. The
      increase in food intake reflects a growth in agricultural production, contrary to
      the standard series of national accounts. We infer from an improved estimate of
      agricultural output, and from the increases in physical stature that the timing
      of the onset of modern economic growth in Italy was substantially different from
      the conventional Gerschenkronian perspective.

PMID- 15463979
TI  - The anthropometric legacy of Franz Boas.
AB  - Franz Boas was responsible for obtaining anthropometric data from approximately
      27,000 subjects living around the turn-of-the-century. The subjects are of Native
      American, Siberian and European ancestry. These data have been entered into
      databases and are available for research. This paper describes the circumstances
      under which these data were collected and discusses their research potential.

PMID- 15463981
TI  - The effects of maternal education versus cognitive test scores on child nutrition
      in Kenya.
AB  - This paper estimates dynamic random effects models for intakes by dietary energy,
      protein, calcium, iron, zinc, niacin, riboflavin, thiamin, and vitamins A, C, D,
      and E 100 of Kenyan school children (6-9 years) within a multivariate
      longitudinal framework. The explanatory variables were socioeconomic and
      background variables, children's body mass index, and maternal education,
      cognitive test scores and morbidity spells. The model parameters are estimated
      using the maximum likelihood method controlling for unobserved between-children
      differences. The main finding is that while maternal education was usually not a
      significant predictor of dietary intakes, maternal scores on cognitive tests did
      strongly predict them. Moreover, the paternal cognitive scores and maternal
      morbidity levels were not significantly associated with the intakes, but an index
      of socioeconomic status and cash income was a significant predictor. The results
      indicate the need to consider broader measures of human development and of
      devising suitable educational programs for women without formal education.

PMID- 15463982
TI  - The cost-effectiveness of health education in improving knowledge and awareness
      about intestinal parasites in rural Bangladesh.
AB  - The impact of regular health education in improving knowledge, attitude and
      practices in the control of intestinal parasites was examined in four rural areas
      of Bangladesh; two areas received health education and the other two areas were
      controls. By the end of the 18-month study households receiving health education
      showed highly significant improvements in knowledge, water and sanitation
      facilities and personal hygiene compared with households in the control areas.
      Improving knowledge by 1% cost between US dollars 0.75 and 0.82 per household,
      while a 1% improvement in personal hygiene cost between US dollars 1.10 and 1.32
      per household and water and sanitation between US dollars 1.39 and 1.52 per
      household.

PMID- 15463983
TI  - Wage rentals for reproducible human capital: evidence from Ghana and the Ivory
      Coast.
AB  - Education, child nutrition, adult health/nutrition, and labor mobility are
      critical factors in achieving recent sustained growth in factor productivity. To
      compare the contribution of these four human capital inputs, an expanded
      specification of the wage function is estimated from household (LSMS) surveys of
      the Ivory Coast and Ghana. Specification tests assess whether the human capital
      inputs are exogenous, and instrumental variable techniques are used to estimate
      the wage function. Smaller panels from the Ivory Coast imply the magnitude of
      measurement error in the human capital inputs and provide more efficient
      instruments to estimate the wage equation. The conclusion emerges that weight-for
      height and height are endogenous, particularly prone to measurement error, and
      heterogeneous in their effects on wages. Overall returns to these four forms of
      human capital are similar within each country for men and women, but education
      and migration returns are higher in the more rapidly growing Ivory Coast, and the
      wage effects of child nutrition proxied by height are greater in poorer, more
      malnourished Ghana.

PMID- 15463984
TI  - Bio-cultural effects in medieval populations.
AB  - Male skeletons from medieval archaeological sites are analysed to assess
      differences in stature and body proportions related to the bio-cultural
      environment, such as social, economic, and health factors. Environmental factors,
      such as climate change in the course of the Middle Ages, did not have
      statistically significant effect on body proportions in these samples. The
      results show a relationship between bio-cultural factors and physique in the
      analysed populations that indicate stunted growth in height and weight in a
      leprosarium population with a low socio-economic and health status. A high-status
      monastic population is characterised by a stocky build, i.e., increased weight
      for height and relatively shorter limbs, while a medieval parish population has a
      linear build, i.e., relatively long limbs for height and decreased weight for
      height. These characteristics, relative weight for height and relative limb
      length, changed during the course of the Middle Ages, as did stature.

PMID- 15463985
TI  - Perinatal mortality in Utrecht, The Netherlands, 1880-1940.
AB  - The secular trend of perinatal mortality in Utrecht between 1880 and 1940 and its
      causes are examined in this study, based on patient records of two maternity
      clinics, those of the city's academic hospital, and of its outpatient clinic. The
      sample includes 17,111 deliveries. Over the period the proportion of births in
      the city occurring in the two institutions rose from 3 to 90%. The perinatal
      mortality rate in the hospital declined and then rose slightly at the end of the
      19th century, but remained constant, even if cyclical, thereafter in both the
      hospital and the outpatient clinic. Rates differed substantially between the two
      maternity services. Logistic regression analysis reveals a cluster of factors
      related to perinatal death. Low birth weight had a powerful association with
      perinatal mortality in both samples. Most of the other factors associated with
      perinatal mortality were related to the health of the patients, to obstetric
      problems related to deliveries, and to infant sex and maternal age. Relationships
      between perinatal mortality and other measures of human welfare in The
      Netherlands are explored.

PMID- 15463986
TI  - Data: archival information available on the health of Alcatraz Federal
      Penitentiary inmates.

PMID- 15463987
TI  - Data: archival information on the physical stature and weight of American men
      during World War I and World War II.
AB  - Millions of observations are available on the height of men who participated in
      the so-called "Forth Registration" of the United States Selective Service
      Administration in World war II. The men were born between April 28, 1877 and
      February 16, 1897.

PMID- 15463988
TI  - Bio-demographic change and socio-economic trends in Bulgaria.
AB  - Recent bio-demographic change in Bulgaria is analysed in conjunction with socio
      economic trends. The exceptionally serious problem of the "ageing population" is
      outlined, and its main socio-economic consequences are discussed. The main reason
      for the population aging is the low fertility rate and the large number of
      emigrants, especially during the last decade. For the population in Bulgaria to
      grow at all, policies need to be adopted to increase the fertility rate, lower
      the emigration rate, and provide incentives for those who have already left the
      country to return. Furthermore, social policies are needed to support the family,
      in order to encourage fertility and improve the social and health status of
      population. The socio-economic crisis that began in the 1990s must be overcome
      before the standard of living can increase.

PMID- 15463990
TI  - A restricted maximum likelihood estimator for truncated height samples.
AB  - A restricted maximum likelihood (ML) estimator is presented and evaluated for use
      with truncated height samples. In the common situation of a small sample
      truncated at a point not far below the mean, the ordinary ML estimator suffers
      from high sampling variability. The restricted estimator imposes an a priori
      value on the standard deviation and freely estimates the mean, exploiting the
      known empirical stability of the former to obtain less variable estimates of the
      latter. Simulation results validate the conjecture that restricted ML behaves
      like restricted ordinary least squares (OLS), whose properties are well
      established on theoretical grounds. Both estimators display smaller sampling
      variability when constrained, whether the restrictions are correct or not. The
      bias induced by incorrect restrictions sets up a decision problem involving a
      bias-precision tradeoff, which can be evaluated using the mean squared error
      (MSE) criterion. Simulated MSEs suggest that restricted ML estimation offers
      important advantages when samples are small and truncation points are high, so
      long as the true standard deviation is within roughly 0.5 cm of the chosen value.

PMID- 15463991
TI  - Macro shocks and micro outcomes: child nutrition during Indonesia's crisis.
AB  - A survey of households in rural Java is used to assess the nutritional impact of
      Indonesia's drought and financial crisis of 1997/1998. A time-age-cohort
      decomposition reveals significant nutritional impacts. However, child weight-for
      age (WAZ) remained constant throughout the crisis, despite rapid increases in
      food prices and the consequent household consumption shock. The evidence is
      consistent with the hypothesis that within households, mothers buffered
      children's caloric intake, resulting in increased maternal wasting. However,
      reductions in the consumption of high-quality foods further resulted in increased
      prevalence of anemia for both mothers and children. The combined effects were
      particularly severe for cohorts conceived and weaned during the crisis.

PMID- 15463992
TI  - Observations on the history of Dutch physical stature from the late-Middle Ages
      to the present.
AB  - In the late-Middle Ages and at the onset of the early modern period, the Dutch
      population was taller than in the first half of the 19th century. This inference
      is partially based on skeletal evidence, mainly collected by the Dutch physical
      anthropologist George Maat and his co-workers. A spectacular increase in Dutch
      heights began in the second half of the 19th century and accelerated in the
      second half of the 20th century. At the end of the 20th century, the Dutch became
      tallest in the world.

PMID- 15463993
TI  - From the tallest to (one of) the fattest: the enigmatic fate of the American
      population in the 20th century.
AB  - Within the course of the 20th century the American population went through a
      virtual metamorphosis from being the tallest in the world, to being among the
      most overweight. The American height advantage over Western and Northern
      Europeans was between 3 and 9 cm in mid-19th century, and Americans tended to be
      underweight. However, today, the exact opposite is the case as the Dutch, Swedes,
      and Norwegians are the tallest, and the Danes, British and Germans--even the East
      Germans--are also taller, towering over the Americans by as much as 3-7 cm.
      Americans also have shorter lives. The hypothesis is worth considering that this
      adverse development is related to the greater social inequality, an inferior
      health care system, and fewer social safety nets in the United States than in
      Western and Northern Europe, in spite of higher per capita income. The Western
      and Northern European welfare states, with cradle to grave health and
      unemployment insurance currently seems to provide a more propitious environment
      for the biological standard of living than its US counterpart.

PMID- 15463994
TI  - The height of Tennessee convicts: another piece of the "antebellum puzzle".
AB  - Average height of the free population in the United States born in the mid-1830s
      began to decline despite growing per capita incomes. Explanations for this
      "antebellum puzzle" revolve around a possibly deteriorating disease environment
      promoted by urban agglomeration and increases in the relative price of protein
      rich foods. However, several groups were immune to the effect, including members
      of the middle class, whose income was high enough, and increased enough to
      overcome the adverse developments and maintain their nutritional status. Although
      at the opposite end of the social spectrum, the height of male slaves also
      increased, as it was in their owners' interest to raise their slaves' food
      allotments. The height of Tennessee convicts, analyzed in this article, also
      increased in the late-1830s, being the third exception to the "antebellum
      puzzle." Mid-19th century Tennessee was integrated into interstate commerce in
      cotton and tobacco and experienced considerable movement of people who would have
      brought with them diseases from elsewhere, hence, it would have been integrated
      into the US disease pool, and the fact that heights did not decline in the 1830s
      is therefore an indication that the antebellum puzzle cannot be explained
      exclusively by the spread of diseases. Yet, Tennessee's economy was quite
      different to that of the rest of the country. Although it did export live swine
      to the South, these exports did not increase during the antebellum decades.
      Hence, Tennessee remained self-sufficient in pork, and consumption of pork did
      not decline. Thus, the evidence presented here is consistent with the economic
      interpretation of the "antebellum puzzle": self-sufficiency in protein production
      protected even the members of the lower-classes of Tennessee from the negative
      externalities associated with the onset of industrialization.

PMID- 15463995
TI  - Socio-economic transition, inequality, and mortality in Lithuania.
AB  - The study assessed inequalities in mortality of Lithuanian urban and rural
      populations throughout the period of socio-economic transition (1990-2000).
      Mortality from major causes of death, except cancers in females, was higher among
      the rural population. Inequality in mortality increased during the period of
      transition, especially among males, mainly due to more rapidly improving health
      of the urban population. Cardiovascular diseases and external causes made the
      largest contribution to the inequality. Differences in mortality of urban and
      rural populations point to greater social and psychological stress affecting the
      rural population, unhealthy life styles, inequities in accessibility of health
      care and lack of preventive programs in rural areas.

PMID- 15463996
TI  - The effect of the economic transition on the body mass index of conscripts in
      Poland.
AB  - The political and socio-economic transition initiated in Poland in the late 1980s
      is still continuing and has affected all social classes as well as all spheres of
      daily life of the people. The impact of this change on nutrition and health is
      examined here, by comparing the body mass index (BMI) of a 10% nationally
      representative sample of male conscripts aged 19 years (18.50-19.49), in 1986 (n
      = 26,396), 1995 (n = 22,612), and 2001 (n = 26,178). Mean BMI of young men did
      not change between 1986 and 1995, but then increased slightly from 22.0 to 22.3
      between 1995 and 2001. There was also a significant and continuous increase in
      the variation of BMI in all social strata across the entire period 1986-2001.
      This effect is attributed to economic modernisation that has allowed increased
      diversity of life styles across occupational groups and between families. Sibship
      size was more important than socio-economic status in explaining variation in BMI
      after the political changes in 1990. The BMI-enhancing effect of small sibship
      size is attributed to nutritional intake, and to changes in food availability
      across the period under study.

PMID- 15463997
TI  - Social inequality and obesity in Czech school children.
AB  - This study uses logistic regressions to consider the effect of social factors,
      physical activity, meal frequency and BMI of parents on children's body mass
      index (BMI) values. Three thousand three hundred and sixty-two children aged 7-11
      years were examined in 38 schools in the Czech Republic. Six anthropometric
      characteristics were assessed in 1999-2000. Most important factors influencing
      children's BMI values were: obesity of both or at least one of the parents, being
      an only child, residence in small communities, and irregular breakfasts.

PMID- 15463998
TI  - On the incidence of diarrhoea among young Indian children.
AB  - Diarrhoea, claiming over three million young lives in the world every year, is
      the second biggest killer of children in developing countries. Using data for
      over 13,000 children in rural India, under the age of 3 years, this paper
      examines the relative effects of the different factors--inter alia the quality of
      the water supply, mother's literacy, housing conditions, and the level of
      development of the villages in which the children lived--contributing to
      diarrhoea. The paper highlights the importance of two factors: that children born
      to undernourished mothers may be more susceptible to infection than children
      whose mothers are well nourished, and that good hygienic practices within the
      home, such as washing hands with soap before feeding a child, can reduce the
      incidence of diarrhoea. The paper also quantifies the relative strength of the
      factors that determine whether mothers do so. The results emphasize the
      importance of mothers being literate, of household affluence and of institutional
      support (through the availability of trained midwives and mother and child
      centres in villages) in promoting domestic hygiene.

PMID- 15463999
TI  - Infant feeding practices and chronic child malnutrition in the Indian states of
      Karnataka and Uttar Pradesh.
AB  - As measured by degree of stunting, close to half of India's children suffer from
      chronic malnutrition and about a quarter from severe chronic malnutrition. Data
      from the 1998-1999 National Family Health Survey (NFHS) are analysed to assess
      whether recommended infant feeding practices help to alleviate the prevalence of
      stunting. The evidence supports some recommended practices, including the advice
      that mother not squeeze the colostrum from her breasts, not use a feeding bottle
      with a nipple, exclusive breastfeeding for the first 4-6 months and feeding
      supplementary foods (solids and mushy foods) at about 7 months, and suggests
      that, for some children, better feeding practices could reduce the prevalence of
      severe stunting by up to 30%. The paper also examines a range of other issues
      related to stunting--whether medical supplementations and inoculations have an
      effect, whether mothers more actively involved in health decisions have less
      stunted children, and the links between stunting, diarrhoea and anaemia. An
      explanation is offered for the positive relationship between using oral
      rehydration salts and stunting.

PMID- 15464000
TI  - Alcohol abuse and suicide attempts among youth.
AB  - This study uses the Youth Risk Behavior Survey (YRBS) and the National
      Comorbidity Survey (NCS) to explore the causal relationship between alcohol abuse
      (binge drinking and clinically defined alcohol use disorders) and suicide
      attempts among youth. We use an empirical approach that allows one to assess the
      possible existence and strength of a causal relationship without relying on
      identifying assumptions. Our results suggest that a causal relationship between
      binge drinking and suicide attempts is very unlikely. The findings, however,
      support a causal relationship between clinically defined alcohol use disorders
      and suicide attempts among girls.

PMID- 15464001
TI  - Height, income, and nutrition in the Netherlands: the second half of the 19th
      century.
AB  - This paper explores the relationship between height and its determinants, paying
      explicit attention to the dynamic nature of the velocity of the growth profile.
      The relationship between height and some measures of income and nutrition is
      characterized by a changing lag pattern in 19th century the Netherlands.

PMID- 15464002
TI  - Economic growth and the biological standard of living in China, 1880-1930.
AB  - Recent scholarship has revised the once pessimistic view of the Chinese economy
      in the late 19th and early 20th centuries, but controversy surrounds the
      distribution effects of economic growth. Did livelihoods improve? Who benefited
      from the growth? Which regions were better off? Past studies infer an improved
      standard of living based on sparse data for wages, the output of cotton textiles
      and movements in grain prices. Height data provide an additional measure of the
      change in welfare, specifically the biological standard of living. This paper
      draws on the health examination records conducted at various Chinese government
      enterprises and agencies during the 1930s and 1940s, and shows a modest
      improvement in this measure of human welfare in some regions of China from the
      1890s to the 1920s.

PMID- 15464003
TI  - Driver's licenses as a source of data on height and weight.
AB  - We investigated the feasibility of using driver's license records to obtain
      height and weight data of individuals. First, we linked Washington State driver's
      license records (DOL) to the state birth files to assess how well driver's
      licenses can be linked to a public health database. We were able to match 78.4%
      of mothers and 71.7% of fathers on birth records to driver's license records.
      Then we assessed the accuracy of DOL height and weight data by comparing them to
      heights and weights measured on control women enrolled in a cancer etiology study
      (CES). There is a close relation between CES and DOL heights, but not a close
      relation between weights. Our results suggest that driver's license files are a
      good source of information for women's heights, but are not as good for women's
      weights.

PMID- 15464004
TI  - Analyzing infant mortality with geoadditive categorical regression models: a case
      study for Nigeria.
AB  - In this paper, we analyze infant mortality in Nigeria based on the data set from
      the 1999 Nigeria Demographic and Health Survey (NDHS). We investigate spatial
      patterns at a highly disaggregated level of Nigerian states and consider non
      linear effects of mother's age at birth. Time to the occurrence of a child's
      death can intuitively be considered to be categorical in nature and the
      determinants of a child's death may differ in different age groups. Thus, it may
      be desirable to investigate separately the death of a child in the first month
      and in the remaining 11 months of the first year of life. To avoid selection
      bias, the data set used for this case study is based on information on children
      who were born 12 months preceding the survey. Inference is Bayesian and is based
      on Markov chain Monte Carlo (MCMC) techniques. We find that spatial variation and
      the determinants of death indeed differ considerably for the two age groups
      considered.

PMID- 15464005
TI  - The socio-economic effects of tropical diseases in Nigeria.
AB  - Urinary schistosomiasis is the most prevalent of the endemic tropical diseases:
      48% of the population is afflicted in the study area. The socio-economic,
      environmental and health-seeking behavioural characteristics of the population
      are conducive to the spread of urinary schistosomiasis. The attitudes considered
      include knowledge of what causes the disease and how to control it, attitude
      toward the disease, care of oneself, hygiene and sanitation. The effect of such
      social variables as stigmatisation, and environmental variables such as water
      source is also considered. We find that a unit increase in the hygiene/sanitation
      index for adult males and adult females lead to a reduction of about 7.3 and 4.0
      eggs S. haematobium in 10 ml urine sample, respectively. Thus, simple hygienic
      activities such as keeping the immediate environment of the household free from
      human wastes contribute substantially to disease control. Furthermore, prevalence
      of the disease is higher among males. Losses from work attributed to urinary
      schistosomiasis are high. Average values of key socio-economic variables-labour
      flow for land clearing, farm size and cash income-computed for farm families with
      high urinary schistosomiasis intensity in the sample are 1085 h, 1.4 ha and N
      1,432 (US dollars 65) respectively. The corresponding figures for farm families
      free from the disease are significantly higher: 1325 h, 1.9 ha and N 3,759 (US
      dollars 171), respectively.

PMID- 15464006
TI  - The relationship between maternal characteristics, birth weight and pre-term
      delivery: evidence from Germany at the end of the 20th century.
AB  - Using data from a sample of German women, this paper analyzes the relationship
      between maternal characteristics and infants' birth weight and pre-term delivery.
      Besides typical epidemiological factors that influence the weight of infants,
      such as the gestational age and maternal BMI at the beginning of the pregnancy,
      we find a West--East gradient. Within West Germany, there is a small North-South
      gradient in birth weight, with larger birth weights in the north. Better educated
      mothers give birth to heavier babies and have a somewhat decreased risk of pre
      term delivery. Income plays a minor role, while occupational status is not
      associated with the weight of infants at all.

PMID- 15464007
TI  - Height, weight and BMI of schoolchildren in Jena, Germany--are the secular
      changes levelling off?
AB  - The secular trend of body height, weight and body mass index (BMI) in 7- to 14
      year-old Jena schoolchildren measured in 1975, 1985, 1995 and 2001 is examined.
      Between 1975 and 1995, a positive trend both in height and weight is observed. In
      the decade 1985-1995, which includes the time of German reunification, weight
      shows considerably greater increases than height, resulting in an increasing
      prevalence of overweight and obesity. The changes in living conditions after
      reunification cause no remarkable intensification of the secular trend in height.
      After 1995, the increase in height of boys decelerates, while among girls even a
      decrease occurs. Girls' weight remains approximately constant between 1995 and
      2001 whereas weight among boys continues to increase. The levelling off of the
      secular increases in height at the end of the twentieth century may be attributed
      to a possible stabilisation of living conditions.

PMID- 15464008
TI  - Children's growth and socio-economic status in Hungary.
AB  - The Hungarian National Growth Study comprises data on 39,035 children and youth
      aged 3-18 years. We examine the relationship between 15 body measurements and
      nine family background variables in this data set. After multiple regression
      analysis which removed curvilinear age effects, family size and population size
      of the place of residence showed consistent associations with the body
      measurements. Children from larger families tended to be shorter on average, and
      have lower weight and skinfold thicknesses whereas children from Budapest were,
      on average, taller and heavier than children from elsewhere with bigger chest and
      calf circumferences and lower skinfold thicknesses. Paternal age, mother's
      profession and birth order showed few associations with body measurements in both
      sexes and father's profession did not associate significantly with any of the
      measurements in boys.

PMID- 15464009
TI  - Socioeconomic determinants of anthropometric trends among Hungarian youth.
AB  - The increase of physical stature in the developed countries and their socio
      economic correlates has been well documented for nearly two centuries. In this
      study, the secular changes in height, weight and the BMI of Hungarian university
      students and conscripts are analyzed for the years 1933-1998. During the first
      half of this period these body measurements changed little, while in the second
      half the rates of change accelerated rapidly: height increased by 1.7 cm among
      males and 1.8 cm among female university students per decade, and 1.8 cm among
      male conscripts. Differences were found according to the place of birth and
      residence as well as parental occupation and educational level.

PMID- 15464010
TI  - Discrete and cyclical movements: unified dynamics or separate control?
AB  - In the literature on motor control, three theoretical perspectives on the
      relation between discrete and cyclical movements may be discerned: (a) cyclical
      movements are concatenated discrete movements; (b) discrete movements are a
      limiting case of cyclical movements, and (c) discrete and cyclical movements are
      motor primitives that may be combined but are irreducible to each other. To
      examine the tenability of these perspectives, 16 participants performed cyclical
      and discrete (flexion and extension) reaching movements of various amplitudes to
      differently sized targets. The kinematic properties of the recorded movements
      were analyzed and compared in detail. The cyclical, ongoing movements differed
      markedly from the discrete movements as well as from the first and last half
      cycles of a bout of cyclical movements, especially in terms of their symmetry
      ratio. These effects were largely independent of amplitude, target size and
      movement direction (flexion-extension). The results obtained ruled out
      perspective (a) and, in principle, left open perspectives (b) and (c). However,
      the observed kinematic features were not readily accounted for by the specific
      dynamical models that have been proposed under perspectives (b) and (c). Future
      modeling attempts should explicate the dynamics of initiation and abortion of
      both discrete and cyclical movements.

PMID- 15464011
TI  - Manual pointing to remembered targets...but also in a remembered visual context.
AB  - In this paper we investigated whether visual background information available
      during target presentation influences manual pointing to remembered targets.
      Younger and older participants manually pointed with their unseen hands to
      remembered or visible targets that were presented or not over a structured
      visible background. The results indicated that a structured visual background
      biased movement planning processes, but did not influence motor control
      processes, regardless of the fact that target location and the background were
      visible or remembered. How one uses visual background information for movement
      planning is not modified by aging.

PMID- 15464012
TI  - Age-related changes in the efficiency of cognitive processing across the life
      span.
AB  - The global-speed and the specific-gain/loss hypotheses have been dominant
      theoretical frameworks in the recent literature on cognitive development and
      aging. Few attempts have been made to explicitly assess the predictive power of
      the two frameworks against each other. We evaluated the extent to which age
      changes in performance in executive function tasks (involving response selection,
      response suppression, working memory, and adaptive control) depend on age-related
      changes in global information-processing speed. Our sample consisted of children,
      adolescents, adults and seniors. Analysis of covariance and structural equation
      modeling revealed a mixed pattern of results. Controlling for global speed
      removed the child vs. adult differences in the speed of responding on the
      executive function tasks but the senior vs. adult differences remained. This
      mixed pattern of findings was interpreted to suggest that the effects of
      advancing age on the speed of responding are mediated by a global mechanism
      during childhood but during senescence the efficiency of executive functioning
      seems particularly vulnerable to the effects of age.

PMID- 15464013
TI  - Gender congruency effects in picture naming.
AB  - The analysis of speech error corpora in various gender-marked languages has shown
      that noun substitutions tend to preserve grammatical gender. This result has been
      taken as an indication that grammatical gender could play a constraining role
      during the process of lexical selection. To gain insights on the status of
      grammatical gender in the speech production system, we discuss this hypothesis
      and we report three picture naming experiments. We attempted to observe gender
      marked context effects in the course of error-free speech production.
      Participants named pictures shortly after processing a prime that was or was not
      gender marked and that was or was not congruent with the name of the picture. A
      clear congruency effect was observed, involving both facilitation in the gender
      congruent conditions and inhibition in gender incongruent conditions. Different
      interpretations of this effect and of previously reported gender context effects
      are discussed in the context of current models of speech production.

PMID- 15464014
TI  - Resolution of conflicts between internal and external information sources on a
      time reproduction task: the role of perceived information reliability and
      attributional style.
AB  - Erroneous knowledge of results (KR) that conflicts with other internal or
      external information sources is preferentially used and misguides performance on
      motor and mental timing tasks. Buekers et al. [J. Motor Behavior 26 (1994) 27]
      hypothesized that KR is used preferentially because participants deem it to be
      the most reliable information source. We tested this hypothesis in two
      experiments. We manipulated subjective reliability of information and information
      content and demonstrated that both reliability and content are assessed and used.
      In a third experiment we examined whether attributional style affected the use of
      internal and external information. While KR was present, attributional style was
      unrelated to performance. However, when erroneous KR was withdrawn, participants
      who scored high in internal attributional style or high in controllability showed
      more accurate performance. Whereas evaluation of information quality is explicit,
      information provided by the KR, whether accurate or not, may influence both
      implicit and explicit aspects of the tasks.

PMID- 15464016
TI  - A review of the mechanisms involved in the acute MDMA (ecstasy)-induced
      hyperthermic response.
AB  - The predominant severe acute adverse effect following ingestion of 3,4
      methylenedioxymethamphetamine (MDMA, ecstasy) by recreational users is
      hyperthermia which can induce other associated clinical problems and occasionally
      death. There is no pharmacologically specific treatment. MDMA also induces dose
      dependent hyperthermia in experimental animals. This review examines the
      consequences of MDMA administration on body temperature in humans and rodents. In
      rats hyperthermia results primarily from dopamine release and is influenced by
      dose, ambient temperature and other housing conditions. The response is increased
      in rats with a prior MDMA-induced neurotoxic lesion of 5-hydroxytryptamine (5-HT)
      nerve endings. Increased MDMA-induced locomotor activity appears to play no role
      in the hyperthermic response. However, the size of the acute hyperthermic
      response plays a major role in determining the severity of the subsequent
      neurotoxicity. These results suggest that any MDMA-induced hyperthermic response
      will be enhanced in hot, crowded dance club conditions and that ingesting the
      drug in such conditions increases the possibility of subsequent cerebral
      neurotoxic effect.

PMID- 15464017
TI  - Mammalian tachykinins and uterine smooth muscle: the challenge escalates.
AB  - We review the actions of mammalian tachykinins on uterine smooth muscle. Derived
      from sensory neurones and non-neuronal cells within the female reproductive
      tract, tachykinins are potent uterotonic agents. Three tachykinin receptor genes,
      and the gene encoding neprilysin, the enzyme that inactivates tachykinins, are
      present in rat, mouse and human myometrium. In rat and human, the tachykinin
      NK(2) receptor is important in mediating the uterotonic effects of tachykinins;
      actions at this receptor remain relatively stable or vary only slightly in the
      face of changing hormonal and gestational status. In contrast, ovarian steroids
      and pregnancy regulate expression of the tachykinin NK(3), and to a lesser
      extent, the tachykinin NK(1) receptor, as well as the activity of neprilysin. In
      the oestrogen primed mouse uterus, the tachykinin NK(1) receptor primarily
      mediates tachykinin uterotonic effects, but there is a switch to the tachykinin
      NK(2) receptor by late pregnancy. The possible physiological and pathological
      roles of tachykinins, including hemokinins and endokinins, in normal and
      premature labour, stress-induced abortion and menstrual disorders are briefly
      discussed.

PMID- 15464018
TI  - Sympathetic co-transmission: the coordinated action of ATP and noradrenaline and
      their modulation by neuropeptide Y in human vascular neuroeffector junctions.
AB  - The historical role of noradrenaline as the predominant sympathetic
      neurotransmitter in vascular neuroeffector junctions has matured to include ATP
      and the modulator action of neuropeptide Y (NPY). Numerous studies with isolated
      blood vessels rings demonstrate the presence of key enzymes responsible for the
      synthesis of ATP, noradrenaline and NPY, their co-storage, and their electrically
      evoked release from sympathetic perivascular nerve terminals. Functional assays
      coincide to demonstrate the integral role of these neurochemicals in sympathetic
      reflexes. In addition, the detection of the diverse receptor populations for ATP,
      noradrenaline and NPY in blood vessels, either in the smooth muscle, endothelial
      cells or nerve endings, further contribute to the notion that sympathetic
      vascular reflexes encompass the orchestrated action of the noradrenaline and ATP,
      and their modulation by NPY. The future clinical opportunities of sympathetic co
      transmission in the control of human cardiovascular diseases will be highlighted.

PMID- 15464019
TI  - Endocannabinoids and food consumption: comparisons with benzodiazepine and opioid
      palatability-dependent appetite.
AB  - The endocannabinoid system consists of several endogenous lipids, including
      anandamide and 2-arachidonoyl-glycerol (2-AG), and constitute a retrograde
      signalling system, which modulates neurotransmitter release and synaptic
      plasticity. Specific brain-type cannabinoid receptors (CB(1)) are widely
      distributed in the central nervous system, and are localized presynaptically.
      Mounting evidence, reviewed here, indicates that cannabinoids can act to increase
      food consumption, and cannabinoid CB(1) receptor antagonists/inverse agonists
      reduce food intake and suppress operant responding for food rewards. Hence,
      endocannabinoids provide the first example of a retrograde signalling system,
      which is strongly implicated in the control of food intake. Benzodiazepine and
      opioid palatability-dependent appetite are well-established processes supported
      by several sources of convergent evidence; they provide pharmacological
      benchmarks against which to evaluate the endocannabinoids. To date, evidence that
      endocannabinoids specifically modulate palatability as an affective evaluative
      process is insufficient and not compelling. Endocannabinoids may have important
      clinical utility in the treatment of human obesity and forms of eating disorders.

PMID- 15464020
TI  - Effects of glucocorticoids on gene transcription.
AB  - Glucocorticoids bind to and activate a cytoplasmic glucocorticoid receptor. The
      activated glucocorticoid receptor translocates into the nucleus and binds to
      specific response elements in the promoter regions of anti-inflammatory genes
      such as lipocortin-1 and secretory leukocyte protease inhibitor (SLPI). However,
      the major anti-inflammatory effects of glucocorticoids appear to be due largely
      to interaction between the activated glucocorticoid receptor and transcription
      factors, notably nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP
      1), that mediate the expression of inflammatory genes. NF-kappaB switches on
      inflammatory genes via a process involving recruitment of transcriptional co
      activator proteins and changes in chromatin modifications such as histone
      acetylation. This process must occur in the correct temporal manner to allow for
      effective inflammatory gene expression to occur. The interactions between NF
      kappaB and the glucocorticoid receptor result in differing effects on histone
      modifications and chromatin remodelling. Drugs that enhance glucocorticoid
      receptor nuclear translocation (long acting beta-agonists) and GR-associated
      histone deacetylases activity (theophylline) have been shown to be effective add
      on therapies. In addition, dissociated glucocorticoids that target NF-kappaB
      preferentially have also been successful in the treatment of allergic disease.

PMID- 15464021
TI  - Interleukin-18 bioactivity: a novel target for immunopharmacological anti
      inflammatory intervention.
AB  - Interleukin-18 is a member of the interleukin-1 family of cytokines with pro
      inflammatory and tumor-suppressive properties. Its ability to potently enhance
      the production of interferon-gamma indicates in particular the crucial function
      of interleukin-18 as an immunomodulatory molecule. In fact, high levels of
      interleukin-18 are detected in human diseases associated with immunoactivation
      including viral or bacterial infections and chronic inflammation. Animal models
      suggest suppression of interleukin-18 bioactivity as a novel therapeutic concept
      specifically for the treatment of chronic inflammatory diseases such as
      rheumatoid arthritis, Crohn's disease, and psoriasis. Here we introduce into the
      biology of interleukin-18 and review immunopharmacological strategies that aim at
      reducing interleukin-18 bioactivity in human disease.

PMID- 15464022
TI  - Force-frequency relationship in intact mammalian ventricular myocardium:
      physiological and pathophysiological relevance.
AB  - The force-frequency relationship (FFR) is an important intrinsic regulatory
      mechanism of cardiac contractility. The FFR in most mammalian ventricular
      myocardium is positive; that is, an increase in contractile force in association
      with an increase in the amplitude of Ca(2+) transients is induced by elevation of
      the stimulation frequency, which reflects the cardiac contractile reserve. The
      relationship is different depending on the range of frequency and species of
      animal. In some species, including rat and mouse, a 'primary-phase' negative FFR
      is induced over the low-frequency range up to approximately 0.5-1 Hz (rat) and 1
      2 Hz (mouse). Even in these species, the FFR over the frequency range close to
      the physiological heart rate is positive and qualitatively similar to that in
      larger mammalian species, although the positive FFR is less prominent. The
      integrated dynamic balance of the intracellular Ca(2+) concentration
      ([Ca(2+)](i)) is the primary cellular mechanism responsible for the FFR and is
      determined by sarcoplasmic reticulum (SR) Ca(2+) load and Ca(2+) flux through the
      sarcolemma via L-type Ca(2+) channels and the Na(+)-Ca(2+) exchanger.
      Intracellular Na(+) concentration is also an important factor in [Ca(2+)](i)
      regulation. In isolated rabbit papillary muscle, over a lower frequency range
      (<0.5 Hz), an increase in duration rather than amplitude of Ca(2+) transients
      appears to be responsible for the increase in contractile force, while over an
      intermediate frequency range (0.5-2.0 Hz), the amplitude of Ca(2+) transients
      correlates well with the increase in contractile force. Over a higher frequency
      range (>2.5 Hz), the contractile force is dissociated from the amplitude of
      Ca(2+) transients probably due to complex cellular mechanisms, including oxygen
      limitation in the central fibers of isolated muscle preparations, while the
      amplitude of Ca(2+) transients increases further with increasing frequency
      ('secondary-phase' negative FFR). Calmodulin (CaM) may contribute to a positive
      FFR and the frequency-dependent acceleration of relaxation, although the role of
      calmodulin has not yet been established unequivocally. In failing ventricular
      myocardium, the positive FFR disappears or is inverted and becomes negative. The
      activation and overexpression of cardiac sarcoplasmic reticulum Ca(2+) ATPase
      (SERCA2a) is able to reverse these abnormalities. Frequency-dependent alterations
      of systolic and diastolic force in association with those of Ca(2+) transients
      and diastolic [Ca(2+)](i) levels are excellent indicators for analysis of cardiac
      excitation-contraction coupling, and for evaluating the severity of cardiac
      contractile dysfunction, cardiac reserve capacity and the effectiveness of
      therapeutic agents in congestive heart failure.

PMID- 15464023
TI  - Regulation and cellular roles of phosphoinositide 5-kinases.
AB  - The membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP(2)), plays
      a critical role in various, apparently very different cellular processes. As
      precursor for second messengers generated by phospholipase C isoforms and class I
      phosphoinositide 3-kinases, PIP(2) is indispensable for cellular signaling by
      membrane receptors. In addition, PIP(2) directly affects the localization and
      activity of many cellular proteins via specific interaction with unique
      phosphoinositide-binding domains and thereby regulates actin cytoskeletal
      dynamics, vesicle trafficking, ion channel activity, gene expression and cell
      survival. The activity and subcellular localization of phosphatidylinositol 4
      phosphate 5-kinase (PIP5K) isoforms, which catalyze the formation of PIP(2), are
      actively regulated by membrane receptors, by phosphorylation and by small GTPases
      of the Rho and ARF families. Spatially and temporally organized regulation of
      PIP(2) synthesis by PIP5K enables dynamic and versatile PIP(2) signaling and
      represents an important link in the execution of cellular tasks by Rho and ARF
      GTPases.

PMID- 15464024
TI  - Amino terminal domain regulation of NMDA receptor function.
AB  - N-Methyl-D-aspartate (NMDA) receptor function is modulated by a wide variety of
      compounds, several of which appear to bind to globular extracellular amino
      terminal subunit domains (ATDs). This review focuses on modulators with putative
      binding sites in ATDs of NMDA receptor subunits, and potential mechanisms by
      which these compounds exert their effects on receptor function. With an overview
      that stresses several themes, we explore evidence that the ATDs of NR2 subunits
      appear to bind modulatory compounds in the cleft of a clamshell-like structure
      that is analogous to the ligand-binding domain. This modulation influences NMDA
      receptor function only partially, is dependent on extracellular pH, and affects
      receptor desensitization. Modulation of the NMDA receptor by the ATD is
      considered within a framework of functional modularity of multisubunit ion
      channels. We also consider the potential importance of the ATD in assembly of the
      receptor.

PMID- 15464025
TI  - The elusive alpha(1D)-adrenoceptor: molecular and cellular characteristics and
      integrative roles.
AB  - alpha(1)-Adrenoceptors seem to play key roles in cardiovascular, genitourinary,
      and central nervous system functions. This review will be focused on alpha(1D)
      adrenoceptors. These receptors have intrinsic activity, and many of the more
      commonly used antagonists are in reality inverse agonists. alpha(1D)
      Adrenoceptors are phosphorylated in the basal state, and the natural agonists,
      adrenaline and noradrenaline, increase their phosphorylation; similar effects are
      induced by direct activation of protein kinase C and through activation of
      nonadrenergic receptors. Interestingly, a large proportion of alpha(1D)
      adrenoceptors are located in intracellular vesicles. Such intracellular location
      can be changed to surface expression through the use of inverse agonists and
      coexpression of alpha(1B)-adrenoceptors, which seem to act as pharmacological
      chaperons for proper plasma membrane insertion. The alpha(1D)-adrenoceptor amino
      terminus seems to contain a signal that keeps the receptor intracellularly, but
      interaction with other proteins may also contribute. The precise relationship
      between the intrinsic activity, phosphorylation, and intracellular location is
      currently unknown. alpha(1D)-Adrenoceptor activation induces contraction in a
      variety of vessels, and a role in the control of blood pressure has been
      suggested. Studies using young prehypertensive and adult spontaneously
      hypertensive rats as well as knockout mice suggest that vascular alpha(1D)
      adrenoceptors are involved in the genesis/maintenance of hypertension.

PMID- 15464026
TI  - Opiate physical dependence and N-methyl-D-aspartate receptors.
AB  - The present review focused the involvement of N-methyl-D-aspartate (NMDA)
      receptors in morphine physical dependence. The increased levels of extracellular
      glutamate, NMDA receptor zeta subunit (NR1) mRNA, NMDA receptor epsilon 1 subunit
      (NR2A) protein, phosphorylated Ca(2+)/calmodulin kinase II (p-CaMKII) protein, c
      fos mRNA, c-Fos protein, are observed in the specific brain areas of mice and/or
      rats showing signs of naloxone-precipitated withdrawal. In preclinical and
      clinical studies, a variety of NMDA receptor antagonists and pretreatment with an
      antisense oligonucleotide of the NR1 have been reported to inhibit the
      development, expression and/or maintenance of opiate physical dependence. In
      contrast to data obtained in adult animals, NMDA receptor antagonists are neither
      effective in blocking the development of opiate dependence nor the expression of
      opiate withdrawal in neonatal rats. In the NMDA receptor-deficient mice, the NR2A
      knockout mice show the marked loss of typical withdrawal abstinence behaviors
      precipitated by naloxone. The rescue of NR2A protein by electroporation into the
      nucleus accumbens of NR2A knockout mice reverses the loss of abstinence
      behaviors. The activation of CaMKII and increased expression of c-Fos protein in
      the brain of animals with naloxone-precipitated withdrawal syndrome are prevented
      by NMDA receptor antagonists, whereas the increased levels of extracellular
      glutamate are not prevented by them. These findings indicate that glutamatergic
      neurotransmission at the NMDA receptor site contributes to the development,
      expression and maintenance of opiate dependence, and suggest that NMDA receptor
      antagonists may be a useful adjunct in the treatment of opiate dependence.

PMID- 15464027
TI  - Acquired QT interval prolongation and HERG: implications for drug discovery and
      development.
AB  - Putative interactions between the Human Ether-a-go-go Related Gene (HERG), QT
      interval prolongation and Torsades de Pointes (TdP) are now integral components
      of any discussion on drug safety. HERG encodes for the inwardly rectifying
      potassium channel (I(Kr)), which is essential to the maintenance of normal
      cardiac function. HERG channel mutations are responsible for one form of familial
      long QT syndrome, a potentially deadly inherited cardiac disorder associated with
      TdP. Moreover, drug-induced (acquired) QT interval prolongation has been
      associated with an increase in the incidence of sudden unexplained deaths, with
      HERG inhibition implicated as the underlying cause. Subsequently, a number of non
      cardiovascular drugs which induce QT interval prolongation and/or TdP have been
      withdrawn. However, a definitive link between HERG, QT interval prolongation and
      arrhythmogenesis has not been established. Nevertheless, this area is subject to
      ever increasing regulatory scrutiny. Here we review the relationship between
      HERG, long QT syndrome and TdP, together with a summary of the associated
      regulatory issues, and developments in pre-clinical screening.

PMID- 15464028
TI  - Effects of capsaicin on visceral smooth muscle: a valuable tool for sensory
      neurotransmitter identification.
AB  - Studying the visceral effects of the sensory stimulant capsaicin is a useful and
      relatively simple tool of neurotransmitter identification and has been used for
      this purpose for approximately 25 years in the authors' and other laboratories.
      We believe that conclusions drawn from experiments on visceral preparations may
      have an impact on studies dealing with the central endings of primary afferent
      neurons, i.e. research on nociception at the spinal level. The present review
      concentrates on the effects of capsaicin--through the transient receptor
      potential vanilloid receptor type 1 (TRPV1) receptor--on innervated
      gastrointestinal, respiratory and genitourinary smooth muscle preparations.
      Tachykinins and calcitonin gene-related peptide (CGRP) are the most widely
      accepted transmitters to mediate "local efferent" effects of capsaicin-sensitive
      nerves in tissues taken from animals. Studies more and more frequently indicate a
      supra-additive interaction of various types of tachykinin receptors (tachykinin
      NK(1), NK(2), NK(3) receptors) in the excitatory effects of capsaicin. There is
      also evidence for a mediating role of ATP, acting on P(2) purinoceptors. Non
      specific inhibitory actions of capsaicin-like drugs have to be taken into
      consideration while designing experiments with these drugs. Results obtained on
      human tissues may be sharply different from those of animal preparations.
      Capsaicin potently inhibits tone and movements of human intestinal preparations,
      an effect mediated by nitric oxide (NO) and/or vasoactive intestinal polypeptide.

PMID- 15464029
TI  - Dopamine receptors in C. elegans.
AB  - Dopamine regulates various physiological functions in the central nervous system
      and the periphery. Dysfunction of the dopamine system is implicated in a wide
      variety of disorders and behaviors including schizophrenia, addiction, and
      attention-deficit hyperactivity disorder. Medications that modulate dopamine
      signaling have therapeutic efficacy on the treatment of these disorders. However,
      the causes of these disorders and the role of dopamine are still unclear.
      Studying the dopamine system in a model organism, such as Caenorhabditis elegans,
      allows the genetic analysis in a simple and well-described nervous system, which
      may provide new insight into the molecular mechanisms of dopamine signaling. In
      this review, we summarize recent findings on pharmacological and biochemical
      properties of the C. elegans dopamine receptors and their physiological role in
      the control of behavior.

PMID- 15464030
TI  - Autonomic receptor systems in the failing and aging human heart: similarities and
      differences.
AB  - Changes in autonomic receptor systems (alpha- and beta-adrenoceptors and
      muscarinic receptors) were compared in the aging and failing human heart. In both
      settings responsiveness of beta-adrenoceptors and all other receptor systems that
      evoke their effects via cyclic AMP accumulation was diminished. Muscarinic
      receptor function, on the other hand, was decreased in the aging, but unchanged
      in the failing heart; in contrast, G protein-coupled receptor kinase activity was
      increased in the failing, but unchanged in the aging heart. alpha-Adrenoceptor
      function was unchanged or slightly decreased in the failing heart. However,
      nothing is known on alpha-adrenoceptor changes in the aging heart. These results
      indicate that in the failing human heart all autonomic receptor systems appear to
      be altered in the direction to attenuate beta-adrenoceptor responses to
      sympathetic (over)stimulation while in the aging human heart autonomic receptor
      systems appear to be altered in a direction that protects the heart against too
      pronounced reduction in beta-adrenoceptor responsiveness.

PMID- 15464031
TI  - Pharmacological effects of green tea on the gastrointestinal system.
AB  - Green tea is rich in polyphenolic compounds, with catechins as its major
      component. Studies have shown that catechins possess diverse pharmacological
      properties that include anti-oxidative, anti-inflammatory, anti-carcinogenic,
      anti-arteriosclerotic and anti-bacterial effects. In the gastrointestinal tract,
      green tea was found to activate intracellular antioxidants, inhibit procarcinogen
      formation, suppress angiogenesis and cancer cell proliferation. Studies on the
      preventive effect of green tea in esophageal cancer have produced inconsistent
      results; however, inverse relationships of tea consumption with cancers of the
      stomach and colon have been widely reported. Green tea is effective to prevent
      dental caries and reduce cholesterols and lipids absorption in the
      gastrointestinal tract, thus benefits subjects with cardiovascular disorders. As
      tea catechins are well absorbed in the gastrointestinal tract and they interact
      synergistically in their disease-modifying actions, thus drinking unfractionated
      green tea is the most simple and beneficial way to prevent gastrointestinal
      disorders.

PMID- 15464032
TI  - Striatal dopamine D2 receptors in modulation of pain in humans: a review.
AB  - We review evidence indicating that the striatum and striatal dopamine D2
      receptors are involved in the regulation of pain in humans. Painful stimulation
      produces an increase in regional cerebral blood flow in the human striatum. Pain
      is a common symptom in patients with nigrostriatal dopaminergic hypofunction.
      Positron emission tomography findings show that a low dopamine D2 receptor
      availability in the striatum of healthy subjects (indicating either a low density
      of dopamine D2 receptors or a high synaptic concentration of dopamine) is
      associated with a high cold pain threshold and a low capacity to recruit central
      pain inhibition by conditioning stimulation. Patients with chronic orofacial pain
      have higher dopamine D2 receptor availability than their age-matched controls. We
      propose that the striatal dopamine D2 receptor may be an important target for the
      diagnosis and treatment of chronic pain.

PMID- 15464033
TI  - Acetylcholine: a novel regulator of airway smooth muscle remodelling?
AB  - Increased airway smooth muscle mass is a pathological feature that asthma and
      chronic obstructive pulmonary disease (COPD) have in common. This increase has
      gained renewed interest in view of recent developments showing that airway smooth
      muscle, instead of solely being a contractile partner, is capable of interacting
      dynamically with its environment, especially under inflammatory conditions.
      Airway smooth muscle cells are able to proliferate, to migrate, and to secrete
      chemokines, cytokines, extracellular matrix proteins and growth factors, and most
      importantly, to adapt to these functions by changing its phenotype from
      contractile to proliferative/synthetic. Conversely, switching to a
      (hyper)contractile phenotype may also occur. A vast number of inflammatory
      stimuli regulate these functions and exert their effects via excitatory G(q) or
      G(i)-coupled receptors. Since acetylcholine activates muscarinic M(2) and M(3)
      receptors in the airway smooth muscle cell membrane, which are coupled to G(i)
      and G(q) proteins, respectively, and since acetylcholine release may be enhanced
      in airway inflammation, a pathophysiological role of acetylcholine related to the
      above processes and exceeding contraction could be envisaged. In this review,
      evidence in favour of this hypothesis, based on recent data that show a role for
      muscarinic receptors in modulating airway smooth muscle proliferation,
      contractility and contractile protein expression is discussed. Based on these
      findings, we postulate that endogenous acetylcholine contributes to airway
      remodeling in asthma and COPD.

PMID- 15464034
TI  - Potassium channels and pain: present realities and future opportunities.
AB  - Four families of potassium channels with different structures, functional
      characteristics and pharmacological sensitivity, are distinguished in neurons:
      voltage-gated (K(v)), calcium-activated (K(Ca)), inward rectifier (K(ir)) and two
      pore (K(2P)) K(+) channels. During the last 15 years, numerous studies have
      demonstrated that the opening of some of these K(+) channels plays an important
      role in the antinociception induced by agonists of many G-protein-coupled
      receptors (alpha(2)-adrenoceptors, opioid, GABA(B), muscarinic M(2), adenosine
      A(1), serotonin 5-HT(1A) and cannabinoid receptors), as well as by other
      antinociceptive drugs (nonsteroidal antiinflammatory drugs [NSAIDs], tricyclic
      antidepressants, etc.) and natural products. Several specific types of K(+)
      channels are involved in antinociception. The most widely studied are the ATP
      sensitive K(+) channels (K(ATP)), members of the K(ir) family, which participate
      in the antinociception induced by many drugs that activate them in both the
      central and the peripheral nervous system. The opening of G-protein-regulated
      inwardly rectifying K(+) channels (GIRK or K(ir)3), K(v)1.1 and two types of
      K(Ca) channels, the small- and large-conductance calcium-activated K(+) channels
      (SK and BK channels, respectively), also play a role in the antinociceptive
      effect of different drugs and natural products. Recently, drugs that open K(+)
      channels by direct activation (such as openers of neuronal K(v)7 and K(ATP)
      channels) have been shown to produce antinociception in models of acute and
      chronic pain, which suggests that other neuronal K(+) channels (e.g. K(v)1.4
      channels) may represent an interesting target for the development of new K(+)
      channel openers with antinociceptive effects.

PMID- 15464035
TI  - Recent pharmacological studies on natural products in China.
AB  - Natural products have been used as medicinal agents for many years. In addition,
      these compounds have also served as the starting points for semisynthetic analogs
      with improved properties. This review focuses on recent advances in the
      pharmacological studies on natural products mainly performed and published in
      China. Emphasis will be placed on those compounds that show the greatest promise
      clinically such as huperzine A (9-amino-13-ethylidene-11-methyl-4
      azatricyclo[7.3.1.0(3.8)]trideca-3(8),6,11-trien-5-one), s-(-)-3-n-butylphthalide
      (s-(-)-3-butyl-1(3H)-isobenzofuranone), (-)-clausenamide (3-hydroxy-4-phenyl-5a
      hydroxybenzyl-N-methyl-gamma-lactam) and Ginkgo biloba extract and its active
      components.

PMID- 15464036
TI  - TRPV1 and the gut: from a tasty receptor for a painful vanilloid to a key player
      in hyperalgesia.
AB  - Capsaicin, the pungent ingredient in red pepper, has been used since ancient
      times as a spice, despite the burning sensation associated with its intake. More
      than 50 years ago, Nikolaus Jancso discovered that capsaicin can selectively
      stimulate nociceptive primary afferent neurons. The ensuing research established
      that the neuropharmacological properties of capsaicin are due to its activation
      of the transient receptor potential ion channel of the vanilloid type 1 (TRPV1).
      Expressed by primary afferent neurons innervating the gut and other organs, TRPV1
      is gated not only by vanilloids such as capsaicin, but also by noxious heat,
      acidosis and intracellular lipid mediators such as anandamide and lipoxygenase
      products. Importantly, TRPV1 can be sensitized by acidosis and activation of
      various pro-algesic pathways. Upregulation of TRPV1 in inflammatory bowel disease
      and the beneficial effect of TRPV1 downregulation in functional dyspepsia and
      irritable bladder make this polymodal nociceptor an attractive target of novel
      therapies for chronic abdominal pain.

PMID- 15464037
TI  - Orphan G protein-coupled receptors and obesity.
AB  - The use of orphan G protein-coupled receptors (GPCRs) as targets to identify new
      transmitters has led over the last decade to the discovery of 12 novel
      neuropeptide families. Each one of these new neuropeptides has opened its own
      field of research, has brought new insights in distinct pathophysiological
      conditions and has offered new potentials for therapeutic applications.
      Interestingly, several of these novel peptides have seen their roles converge on
      one physiological response: the regulation of food intake and energy expenditure.
      In this manuscript, we discuss four deorphanized GPCR systems, the ghrelin,
      orexins/hypocretins, melanin-concentrating hormone (MCH) and neuropeptide
      B/neuropeptide W (NPB/NPW) systems, and review our knowledge of their role in the
      regulation of energy balance and of their potential use in therapies directed at
      feeding disorders.

PMID- 15464038
TI  - Regulation of the expression of inducible nitric oxide synthase.
AB  - The role of nitric oxide (NO) generated by the inducible isoform of nitric oxide
      synthase (iNOS) is very complex. Induction of iNOS expression and hence NO
      production has been described to have beneficial antiviral, antiparasital,
      microbicidal, immunomodulatory, and antitumoral effects. However, induced at the
      wrong place or at the wrong time, iNOS has detrimental consequences and seems to
      be involved in the pathophysiology of different human diseases. The pathways
      regulating iNOS expression seem to vary in different cells or different species.
      In general, activation of the transcription factors nuclear factor (NF)-kappaB
      and signal transducer and activator of transcription (STAT)-1alpha and thereby
      activation of the iNOS promoter seems to be an essential step in the regulation
      of iNOS expression in most cells. Also, post-transcriptional mechanisms are
      critically involved in the regulation of iNOS expression.

PMID- 15464039
TI  - Advances in pharmacogenomics and individualized drug therapy: exciting challenges
      that lie ahead.
AB  - Between the 1930s and 1990s, several dozen predominantly monogenic, high
      penetrance disorders involving pharmacogenetics were described, fueling the
      crusade that gene-drug interactions are quite simple. Then, in 1990, the Human
      Genome Project was established; in 1995, the term pharmacogenomics was
      introduced; finally, the complexities of determining an unequivocal phenotype, as
      well as an unequivocal genotype, have recently become apparent. Since 1965, more
      than 1000 reviews on this topic have painted an overly optimistic picture
      suggesting that the advent of individualized drug therapy used by the practicing
      physician is fast approaching. For many reasons listed here, however, we
      emphasize that these high expectations must be tempered. We now realize that the
      nucleotide sequence of the genome represents only a starting point from which we
      must proceed to a more difficult stage: knowledge of the function encoded and how
      this affects the phenotype. To achieve individualized drug therapy, a high level
      of accuracy and precision is required of any clinical test proposed in human
      patients. Finally, we suggest that metabonomics, perhaps in combination with
      proteomics, might complement genomics in eventually helping us to achieve
      individualized drug therapy.

PMID- 15464040
TI  - Role of the betaine/GABA transporter (BGT-1/GAT2) for the control of epilepsy.
AB  - Inactivation of gamma-aminobutric acid (GABA) as a neurotransmitter is mediated
      by diffusion in the synaptic cleft followed by binding to transporter sites and
      translocation into the intracellular compartment. The GABA transporters of which
      four subtypes have been cloned (GAT1-4) are distributed at presynaptic nerve
      endings as well as extrasynaptically on astrocytic and neuronal elements. This
      anatomical arrangement of the transporters appears to be of critical functional
      importance for the maintenance of GABAergic neurotransmission. Pharmacological
      characterization of the GABA transporters using a large number of GABA analogs
      having restricted conformation and lipophilic character has been of instrumental
      importance for elucidation of the functional importance of the different
      transporters. One such analog EF1502 (N-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3
      hydroxy-4-methylamino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol) has been shown to
      selectively inhibit GAT1 (GABA transporter 1) and GAT2/BGT-1 (betaine/GABA
      transporter). Moreover, this GABA analog exhibits an unusually high efficiency as
      an anticonvulsant suggesting a novel role of the betaine/GABA transporter in
      epileptic seizure control. It is hypothesized that extrasynaptic actions of GABA
      may be involved in this phenomenon.

PMID- 15464041
TI  - The endocannabinoid-CB(1) receptor system in pre- and postnatal life.
AB  - Recent research suggests that the endogenous cannabinoids ("endocannabinoids")
      and their cannabinoid receptors have a major influence during pre- and postnatal
      development. First, high levels of the endocannaboid anandamide and cannabinoid
      receptors are present in the preimplantation embryo and in the uterus, while a
      temporary reduction of anandamide levels is essential for embryonal implantation.
      In women accordingly, an inverse association has been reported between fatty acid
      amide hydrolase (the anandamide degrading enzyme) in human lymphocytes and
      miscarriage. Second, CB(1) receptors display a transient presence in white matter
      areas of the pre- and postnatal nervous system, suggesting a role for CB(1)
      receptors in brain development. Third, endocannabinoids have been detected in
      maternal milk and activation of CB(1) receptors appears to be critical for milk
      sucking by newborn mice, apparently activating oral-motor musculature. Fourth,
      anandamide has neuroprotectant properties in the developing postnatal brain.
      Finally, prenatal exposure to the active constituent of marihuana (Delta(9)
      tetrahydrocannabinol) or to anandamide affects prefrontal cortical functions,
      memory and motor and addictive behaviors, suggesting a role for the
      endocannabinoid CB(1) receptor system in the brain structures which control these
      functions. Further observations suggest that children may be less prone to
      psychoactive side effects of Delta(9)-tetrahydrocannabinol or endocannabinoids
      than adults. The medical implications of these novel developments are far
      reaching and suggest a promising future for cannabinoids in pediatric medicine
      for conditions including "non-organic failure-to-thrive" and cystic fibrosis.

PMID- 15464042
TI  - Vascular protection by dietary polyphenols.
AB  - Consumption of polyphenol-rich foods, such as fruits and vegetables, and
      beverages derived from plants, such as cocoa, red wine and tea, may represent a
      beneficial diet in terms of cardiovascular protection. Indeed, epidemiological
      studies demonstrate a significant inverse correlation between polyphenol
      consumption and cardiovascular risk. Among the numerous plausible mechanisms by
      which polyphenols may confer cardiovascular protection, improvement of the
      endothelial function and inhibition of angiogenesis and cell migration and
      proliferation in blood vessels have been the focus of recent studies. These
      studies have indicated that, in addition to and independently from their
      antioxidant effects, plant polyphenols (1) enhance the production of vasodilating
      factors [nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and
      prostacyclin] and inhibit the synthesis of vasoconstrictor endothelin-1 in
      endothelial cells; and (2) inhibit the expression of two major pro-angiogenic
      factors, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2
      (MMP-2) in smooth muscle cells. The mechanisms of these effects involve: (1) in
      endothelial cells, increased Ca(2+) level and redox-sensitive activation of the
      phosphoinositide 3 (PI3)-kinase/Akt pathway (leading to rapid and sustained
      activation of nitric oxide synthase and formation of EDHF) and enhanced
      expression of nitric oxide synthase; and (2) in smooth muscle cells, both redox
      sensitive inhibition of the p38 mitogen-activated protein kinase (p38 MAPK)
      pathway activation (leading to inhibition of platelet-derived growth factor
      (PDGF)-induced VEGF gene expression) and redox-insensitive mechanisms (leading to
      inhibition of thrombin-induced MMP-2 formation). The current evidence suggests
      that all these mechanisms are triggered by polyphenols with specific structures,
      although the structural requirements may be different from one effect to the
      other, and that they all contribute to the vasoprotective, anti-angiogenic, anti
      atherogenic, vasorelaxant and anti-hypertensive effects of acute or chronic
      administration of plant polyphenols found in vivo in animals and in patients.

PMID- 15464043
TI  - Calcitonin gene-related peptide and its role in migraine pathophysiology.
AB  - Migraine is a common neurological disorder that is associated with an increase in
      plasma calcitonin gene-related peptide (CGRP) levels. CGRP, a neuropeptide
      released from activated trigeminal sensory nerves, dilates intracranial blood
      vessels and transmits vascular nociception. Therefore, it is propounded that: (i)
      CGRP may have an important role in migraine pathophysiology, and (ii) inhibition
      of trigeminal CGRP release or CGRP-induced cranial vasodilatation may abort
      migraine. In this regard, triptans ameliorate migraine headache primarily by
      constricting the dilated cranial blood vessels and by inhibiting the trigeminal
      CGRP release. In order to explore the potential role of CGRP in migraine
      pathophysiology, the advent of a selective CGRP receptor antagonist was
      obligatory. The introduction of di-peptide CGRP receptor antagonists, namely
      BIBN4096BS (1-piperidinecarboxamide, N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1
      piperazinyl]carbonyl] pentyl] amino]-1-[(3,5-dibromo-4-hydroxyphenyl) methyl]-2
      oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-, [R-(R*,S*)]-), is a
      breakthrough in CGRP receptor pharmacology and can be used as a tool to
      investigate the role of CGRP in migraine headaches. Preclinical investigations in
      established migraine models that are predictive of antimigraine activity have
      shown that BIBN4096BS is a potent CGRP receptor antagonist and that it has
      antimigraine potential. Indeed, a recently published clinical study has reported
      that BIBN409BS is effective in treating acute migraine attacks without
      significant side effects. The present review will discuss mainly the potential
      role of CGRP in the pathophysiology of migraine and the various treatment
      modalities that are currently available to target this neuropeptide.

PMID- 15464044
TI  - Opioid abuse and brain gene expression.
AB  - Opiate addiction is a central nervous system disorder of unknown mechanism.
      Neuronal basis of positive reinforcement, which is essential to the action of
      opioids, relies on activation of dopaminergic neurons resulting in an increased
      dopamine release in the mesolimbic brain structures. Certain aspects of opioid
      dependence and withdrawal syndrome are also related to the activity of
      noradrenergic and serotonergic systems, as well as to both excitatory and
      inhibitory amino acid and peptidergic systems. The latter pathways have been
      recently proven to be involved both in the development of dependence and in
      counteracting the states related to relapse. An important role in neurochemical
      mechanisms of opioid reward, dependence and vulnerability to addiction has been
      ascribed to endogenous opioid peptides, particularly those acting via the mu- and
      kappa-opioid receptors. Opiate abuse leads to adaptive reactions in the nervous
      system which occur at the cellular and molecular levels. Recent research
      indicates that intracellular mechanisms of signal transmission-from the receptor,
      through G proteins, cyclic AMP, MAP kinases to transcription factors--also play
      an important role in opioid tolerance and dependence. The latter link in this
      chain of reactions may modify synthesis of target genes and in this manner, it
      may be responsible for opiate-induced long-lasting neural plasticity.

PMID- 15464045
TI  - The role of the vanilloid (capsaicin) receptor (TRPV1) in physiology and
      pathology.
AB  - The cloning of the vanilloid receptor 1 opened a floodgate for discoveries
      regarding the function of this complex molecule. It has been found that, in
      addition to heat, protons and vanilloids, this receptor also responds to various
      endogenous ligands. Furthermore, it has been also emerged that, through
      associations with other molecules, the vanilloid receptor 1 plays an important
      role in the integration of various stimuli and modulation of cellular
      excitability. Although, originally, the vanilloid receptor 1 was associated with
      nociceptive primary afferent fibres, it has been gradually revealed that it is
      broadly expressed in the brain, epidermis and visceral cells. The expression
      pattern of the vanilloid receptor 1 indicates that it could be involved in
      various physiological functions and in the pathomechanisms of diverse diseases.
      Here, we summarise the molecular, pharmacological and physiological
      characteristics, and putative functions, of the vanilloid receptor 1, and discuss
      the therapeutic potential of this molecule.

PMID- 15464046
TI  - The role of monoamines in the actions of established and "novel" antidepressant
      agents: a critical review.
AB  - Monoaminergic pathways are highly responsive to aversive stimuli and play a
      crucial role in the control of affect, cognition, endocrine secretion,
      chronobiotic rhythms, appetite, and motor function, all of which are profoundly
      disrupted in depressive states. Accordingly, a perturbation of monoaminergic
      transmission is implicated in the aetiology of depressive disorders, and all
      clinically available antidepressants increase corticolimbic availability of
      monoamines. However, their limited efficacy, delayed onset of action, and
      undesirable side effects underlie ongoing efforts to identify improved
      therapeutic agents. Sequencing the human genome has raised the hope not only of
      better symptomatic control of depression, but even of the prevention or cure of
      depressive states. In the pursuit of these goals, there is currently a tendency
      to focus on selective ligands of "novel" nonmonoaminergic targets. However,
      certain classes of novel agent (such as neurokinin(1) receptor antagonists)
      indirectly modulate the activity of monoaminergic networks. Others may act
      "downstream" of them, converging onto common cellular substrates controlling gene
      expression, synaptic plasticity, and neurogenesis. Further, by analogy to the
      broad-based actions of currently employed drugs, multitarget agents may be better
      adapted than selective agents to the management of depression-a complex disorder
      with hereditary, developmental, and environmental origins. It is, thus, important
      to continue the creative exploration of clinically validated and innovative
      monoaminergic strategies within a multitarget framework. In this light, drugs
      combining monoaminergic and nonmonoaminergic mechanisms of action may be of
      particular interest. The present article provides a critical overview of
      monoaminergic strategies for the treatment of depressive states, both established
      and under development, and discusses interactions of novel "nonmonoaminergic"
      antidepressants with monoaminergic mechanisms.

PMID- 15464047
TI  - Proteomic approaches in brain research and neuropharmacology.
AB  - Numerous applications of genomic technologies have enabled the assembly of
      unprecedented inventories of genes, expressed in cells under specific
      physiological and pathophysiological conditions. Complementing the valuable
      information generated through functional genomics with the integrative knowledge
      of protein expression and function should enable the development of more
      efficient diagnostic tools and therapeutic agents. Proteomic analyses are
      particularly suitable to elucidate posttranslational modifications, expression
      levels and protein-protein interactions of thousands of proteins at a time. In
      this review, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)
      investigations of brain tissues in neurodegenerative diseases such as Alzheimer's
      disease, Down syndrome and schizophrenia, and the construction of 2D-PAGE
      proteome maps of the brain are discussed. The role of the Human Proteome
      Organization (HUPO) as an international coordinating organization for proteomic
      efforts, as well as challenges for proteomic technologies and data analysis are
      also addressed. It is expected that the use of proteomic strategies will have
      significant impact in neuropharmacology over the coming decade.

PMID- 15464048
TI  - Cytokine-induced sickness behaviour: a neuroimmune response to activation of
      innate immunity.
AB  - Sickness refers to a coordinated set of subjective, behavioural and physiological
      changes that develop in sick individuals during the course of an infection. These
      changes are due to the effects of interleukin-1 (IL-1) and other proinflammatory
      cytokines on brain cellular targets. Sickness behaviour is mediated by
      proinflammatory cytokines that are temporarily expressed in the brain during
      infection. These centrally produced cytokines are the same as those expressed by
      innate immune cells and they act on brain receptors that are identical to those
      characterized on immune cells. Primary afferent nerves represent the main
      communication pathway between peripheral and central cytokines. Proinflammatory
      cytokines modulate learning and memory processes. The expression and action of
      proinflammatory cytokines in the brain in response to peripheral cytokines are
      regulated by various molecular intermediates including anti-inflammatory
      cytokines such as interleukin-10 (IL-10) and the IL-1 receptor antagonist (IL
      1ra), growth factors such as insulin-like growth factor-1 (IGF-1), hormones such
      as glucocorticoids and neuropeptides such as vasopressin and alpha-melanotropin.

PMID- 15464049
TI  - Modulation of GABA(A) receptor gene expression by allopregnanolone and ethanol.
AB  - Expression of specific gamma-aminobutyric acid type A (GABA(A)) receptor subunit
      genes in neurons is affected by endogenous modulators of receptor function such
      as neuroactive steroids. This effect of steroids appears to be mediated through
      modulation of GABA(A) receptor signalling mechanisms that control the expression
      of specific receptor subunit genes. Furthermore, the specific outcomes of such
      signalling appear to differ among neurons in different regions of the brain.
      Neuroactive steroids such as the progesterone metabolite allopregnanolone might
      thus exert differential effects on GABA(A) receptor plasticity in distinct
      neuronal cell populations, likely accounting for some of the physiological
      actions of these compounds. Here we summarise experimental data obtained both in
      vivo and in vitro that show how fluctuations in the concentration of
      allopregnanolone regulate both the expression and function of GABA(A) receptors
      and consequently affect behaviour. Such regulation is operative both during
      physiological conditions such as pregnancy and lactation as well as in
      pharmacologically induced states such as pseudopregnancy and long-term treatment
      with steroid derivatives or anxiolytic-hypnotic drugs. Accordingly, long-lasting
      exposure of GABA(A) receptors to ethanol, as well as its withdrawal, induces
      marked effects on receptor structure and function. These results suggest the
      possible synergic action between endogenous steroids and ethanol in modulating
      the functional activity of specific neuronal populations.

PMID- 15464050
TI  - Mechanisms underlying intestinal injury induced by anti-inflammatory COX
      inhibitors.
AB  - By far the most attention has been paid to the deleterious actions of
      nonsteroidal anti-inflammatory drugs (NSAIDs), including isoform selective agents
      that inhibit cyclooxygenase (COX), on the upper gastrointestinal tract,
      particularly the gastric and duodenal mucosa. However, recent studies confirm a
      relatively high incidence of serious clinical events, especially with the more
      established drugs of this class, involving the small intestine. Pathogenic
      factors that have been proposed from early studies in such enteropathy have
      included the enterohepatic circulation of the nonsteroidal anti-inflammatory
      drugs, inhibition of cyclooxygenase, surface epithelial changes and focal
      microvascular events. More recent work has concerned the role of infiltrating
      inflammatory cells, the relative roles of cyclooxygenase isoforms, COX-1 and COX
      2 and the key involvement of inducible nitric oxide (NO) synthase and its product
      in combination with superoxide, peroxynitrite. In the present review, evidence
      for the underlying involvement of each these processes, and their sequential
      integration in the development of the intestinal injury and ulceration promoted
      by nonsteroidal anti-inflammatory drugs has been considered.

PMID- 15464051
TI  - Anxioselective anxiolytics: can less be more?
AB  - Benzodiazepines remain widely used for the treatment of anxiety disorders despite
      a side-effect profile that includes sedation, myorelaxation, amnesia, and ataxia,
      and the potential for abuse. gamma-Aminobutyric acid(A) (GABA(A)) receptor
      partial agonists, subtype-selective agents, and compounds combining both of these
      features are being developed in an attempt to achieve benzodiazepine-like
      efficacy without these potentially limiting side effects. This article reviews
      the nonclinical and clinical studies of "anxioselective" anxiolytics that target
      GABA(A) receptors and discusses potential mechanisms subserving an anxioselective
      profile.

PMID- 15464052
TI  - Nerve growth factor and its receptors in asthma and inflammation.
AB  - Nerve growth factor (NGF) is a high molecular weight peptide that belongs to the
      neurotrophin family. It is synthesized by various structural and inflammatory
      cells and activates two types of receptors, the TrkA (tropomyosin-receptor kinase
      A) receptor and the p75(NTR) receptor, in the death receptor family. NGF was
      first studied for its essential role in neuronal growth and survival. Recent
      reports indicate that it may also help mediate inflammation, especially in the
      airways. Several studies in animals have reported that NGF may induce bronchial
      hyperresponsiveness, an important feature of asthma, by increasing sensory
      innervation. It may also induce migration and activation of inflammatory cells,
      which infiltrate the bronchial mucosa, and of structural cells, including
      epithelial, smooth muscle cells and pulmonary fibroblasts. Increased NGF
      expression and release is observed in asthma patients after bronchial provocation
      with allergen. Taken together, the data from the literature suggest that NGF may
      play a role in inflammation, bronchial hyperresponsiveness and airway remodelling
      in asthma and may help us to understand the neuro-immune cross-talk involved in
      chronic inflammatory airway diseases.

PMID- 15464053
TI  - Putative roles of kinin receptors in the therapeutic effects of angiotensin 1
      converting enzyme inhibitors in diabetes mellitus.
AB  - The role of endogenous kinins and their receptors in diabetes mellitus is being
      confirmed with the recent developments of molecular and genetic animal models.
      Compelling evidence suggests that the kinin B(2) receptor is organ-protective and
      partakes to the therapeutic effects of angiotensin 1-converting enzyme inhibitors
      (ACEI) and angiotensin AT(1) receptor antagonists. Benefits derive primarily from
      vasodilatory, antihypertensive, antiproliferative, antihypertrophic,
      antifibrotic, antithrombotic and antioxidant properties of kinin B(2) receptor
      activation. Mechanisms include the formation of nitric oxide and prostacyclin and
      the inhibition of NAD(P)H oxidase activity involving classical and novel
      signalling pathways. Kinin B(2) receptor also ameliorates insulin resistance by
      increasing glucose uptake and supply, and by inducing glucose transporter-4
      translocation either directly or through phosphorylation of insulin receptor. The
      kinin B(1) receptor, which is induced by the cytokine network, growth factors and
      hyperglycaemia, mediates hyperalgesia, vascular hyperpermeability and leukocytes
      infiltration in diabetic animals. However, emerging data highlight reno- and
      cardio-protective effects mediated by kinin B(1) receptor under chronic ACEI
      therapy in diabetes mellitus. Thus, the Janus-faced of kinin receptors needs to
      be taken into account in future drug development. For instance, locally acting
      kinin B(1)/B(2) receptor agonists if used in a safe therapeutic window may
      represent a more rationale strategy in the prevention and management of diabetic
      complications. Because kinin B(2) receptor antagonists may further increase
      insulin resistance, the persisting dogma that restricts the development of kinin
      receptor analogues to antagonists (that is still relevant to abrogate pain and
      inflammation) needs to be revisited.

PMID- 15464054
TI  - Opioid control of MAP kinase cascade.
AB  - Activation of G protein-coupled receptors (GPCRs) may result in phosphorylation
      of extracellular signal-regulated kinases 1/2 (ERK 1/2). The signaling pathway
      involves ectodomain shedding, generating epidermal growth factor (EGF)-like
      ligands, which in turn stimulate the mitogen-activated protein kinase (MAPK) via
      EGF receptors. The present study investigates into the control of MAPKs by
      opioidergic GPCRs in human embryonic kidney cells (HEK 293). Experiments were
      conducted with cells expressing opioid receptors, G protein-coupled receptor
      kinases, and ERKs. The outcome of our studies let us suggest that EGF-like
      ligands released by opioid receptor stimulation utilize different EGF receptors
      to phosphorylate ERKs, while EGF utilizes type 1 receptors. Differences between
      multiple opioid receptors are apparent with respect to the activation of ERKs.
      EGF rapidly triggers internalization of the fluorescent EGF receptor type 1, but
      we failed to observe any sequestration of this receptor type upon exposure of
      cells to an opioid, since opioids most likely trigger stimulation of a different
      EGF receptor type. In conclusion, G protein-coupled opioid receptors control the
      MAPK cascade in a similar fashion as described for non-opioid GPCRs, although
      distinct differences exist between mu-, delta- and kappa-receptors. EGF-induced
      ERK activation is mediated by EGF receptor type 1 while opioid receptor
      activation seems to brings about stimulation via EGF receptor type.

PMID- 15464055
TI  - Further evidence for the functional role of nonsynaptic nicotinic acetylcholine
      receptors.
AB  - The function of nicotinic acetylcholine receptors in the main central systems has
      been documented in the past decade. These studies focused mostly on the synaptic
      functions, although acetylcholine is released dominantly into the extrasynaptic
      space and the majority of nicotinic acetylcholine receptors on remote neurons are
      found on extrasynaptic membranes. Here, we show further evidence for the role of
      nonsynaptic nicotinic functions in the cognitive and the reward system. Dendrites
      of gamma-amino-n-butyric acid (GABA)-containing interneurons of the hippocampus
      are densely equipped with nicotinic acetylcholine receptors. These cells play an
      important role in memory processing. We analysed the effects of nicotinic
      acetylcholine receptor stimulation on the Ca(2+) dynamics of interneurons in
      different dendritic compartments. We also investigated the role of nicotinic
      receptors in the nucleus accumbens where nicotine stimulated vesicular dopamine
      release via activation of receptors located on varicosities. Nicotine produced
      comparable effects with 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) on
      dopamine release. These examples demonstrate that nonsynaptic nicotinic
      acetylcholine receptors can effectively influence activity pattern of neural
      networks in key structures of central systems.

PMID- 15464056
TI  - Therapeutic applications of chymase inhibitors in cardiovascular diseases and
      fibrosis.
AB  - Chymase activates not only angiotensin I to angiotensin II but also latent
      transforming growth factor-beta-binding protein to transforming growth factor
      beta. In dog grafted veins, chymase activity and angiotensin II concentration
      along with vascular proliferation were significantly increased, while they were
      significantly suppressed by a chymase inhibitor. After balloon injury in dog
      arteries, chymase activity was significantly increased in the injured artery, and
      a chymase inhibitor and an angiotensin AT(1) receptor antagonist were effective
      in preventing the vascular proliferation, but an angiotensin-converting enzyme
      inhibitor was ineffective. In fibrotic models, the tissue fibrosis was reduced by
      chymase inhibitors. In adhesion models, the transforming growth factor-beta
      concentration and adhesion formation were suppressed by chymase inhibitors.
      Therefore, chymase inhibitors may be useful for preventing cardiovascular
      diseases and fibrosis via inhibition of angiotensin II formation and transforming
      growth factor-beta activation.

PMID- 15464057
TI  - Cyclooxygenase inhibition in human monocytes increases endotoxin-induced TNF
      alpha without affecting cyclooxygenase-2 expression.
AB  - Human endotoxin-stimulated adherent monocytes were used in order to determine
      whether or not NSAIDs influence cyclooxygenase-2 and/or tumor necrosis factor
      (TNF)alpha expression within the range of inhibitor concentrations that are
      required to suppress prostaglandin biosynthesis. Exogenous prostaglandin E(2)
      (IC(50)<5 nM) inhibited endotoxin-induced TNFalpha mRNA and protein while, up to
      1 microM, it did not significantly affect cyclooxygenase-2 mRNA expression.
      Similar results were obtained using the membrane-permeable cAMP analogue db-cAMP,
      which caused preferential inhibition of TNFalpha expression. Indomethacin or
      lysine-acetylsalicylic acid concentration-dependently inhibited prostaglandin
      E(2) biosynthesis and, at concentrations causing near-complete inhibition,
      enhanced TNFalpha mRNA and protein expression without significantly influencing
      cyclooxygenase-2 mRNA. In addition, by facilitating endotoxin-induced TNFalpha
      expression, indomethacin or lysine-acetylsalicylic acid counteracted
      dexamethasone-induced inhibition of TNFalpha biosynthesis, thereby exhibiting an
      effect opposite to that of exogenous prostaglandin E(2). The results suggest that
      in human endotoxin-stimulated monocytes, NSAIDs can enhance TNFalpha expression
      through inhibition of cyclooxygenase and the resulting decrease in prostanoid
      biosynthesis.

PMID- 15464058
TI  - Antitumor effect of avermectins.
AB  - The effect of a mixture of naturally occurring aversectin C and avermectin B(1)
      on the growth of ascites and solid experimental tumors of mice was studied. It
      was shown for the first time that avermectins possess a pronounced antitumor
      action. When added at nontoxic doses, they significantly suppressed the growth of
      ascites Ehrlich carcinoma and P388 lympholeukemia and solid Ehrlich and 755
      carcinomata. With some administration regimens, avermectins suppressed the tumor
      growth by 70-80%. Avermectins were most effective when injected
      intraperitoneally. It was also shown that avermectins enhanced the vincristine
      induced suppression of the growth of Ehrlich carcinoma, melanoma B16, and P388
      lympholeukemia. Avermectins produced this effect only when injected after
      vincristine.

PMID- 15464059
TI  - Effect of melatonin on the generation of nitric oxide in murine macrophages.
AB  - In the present investigation, the effects of melatonin on the generation of
      nitric oxide in stimulated murine macrophages were studied by electron
      paramagnetic resonance techniques, and the underlying mechanisms were discussed.
      Upon stimulation with lipopolysaccharide/interferon-gamma, macrophages generated
      a high concentration of nitric oxide. Melatonin pretreatment significantly
      inhibited the generation of nitric oxide. Western blot and reverse transcription
      polymerase chain reaction analysis showed that melatonin decreased the expression
      of inducible nitric oxide synthase at either the protein or mRNA level. Further
      investigation showed that melatonin significantly attenuated the nitration of
      cytoplasmic IkappaB-alpha, inhibited the degradation of IkappaB-alpha, and
      blocked the translocation of p65/RelA into the nuclei. The results suggest that
      melatonin inhibits the expression of inducible nitric oxide synthase by
      modulating the nuclear factor kappaB pathway.

PMID- 15464060
TI  - The putative imidazoline receptor agonist, harmane, promotes intracellular
      calcium mobilisation in pancreatic beta-cells.
AB  - beta-Carbolines (including harmane and pinoline) stimulate insulin secretion by a
      mechanism that may involve interaction with imidazoline I(3)-receptors but which
      also appears to be mediated by actions that are additional to imidazoline
      receptor agonism. Using the MIN6 beta-cell line, we now show that both the
      imidazoline I(3)-receptor agonist, efaroxan, and the beta-carboline, harmane,
      directly elevate cytosolic Ca(2+) and increase insulin secretion but that these
      responses display different characteristics. In the case of efaroxan, the
      increase in cytosolic Ca(2+) was readily reversible, whereas, with harmane, the
      effect persisted beyond removal of the agonist and resulted in the development of
      a repetitive train of Ca(2+)-oscillations whose frequency, but not amplitude, was
      concentration-dependent. Initiation of the Ca(2+)-oscillations by harmane was
      independent of extracellular calcium but was sensitive to both dantrolene and
      high levels (20 mM) of caffeine, suggesting the involvement of ryanodine receptor
      gated Ca(2+)-release. The expression of ryanodine receptor-1 and ryanodine
      receptor-2 mRNA in MIN6 cells was confirmed using reverse transcription
      polymerase chain reaction (RT-PCR) and, since low concentrations of caffeine (1
      mM) or thimerosal (10 microM) stimulated increases in [Ca(2+)](i), we conclude
      that ryanodine receptors are functional in these cells. Furthermore, the increase
      in insulin secretion induced by harmane was attenuated by dantrolene, consistent
      with the involvement of ryanodine receptors in mediating this response. By
      contrast, the smaller insulin secretory response to efaroxan was unaffected by
      dantrolene. Harmane-evoked changes in cytosolic Ca(2+) were maintained by
      nifedipine-sensitive Ca(2+)-influx, suggesting the involvement of L-type voltage
      gated Ca(2+)-channels. Taken together, these data imply that harmane may interact
      with ryanodine receptors to generate sustained Ca(2+)-oscillations in pancreatic
      beta-cells and that this effect contributes to the insulin secretory response.

PMID- 15464061
TI  - Prodelphinidin B-2 3,3'-di-O-gallate from Myrica rubra inhibits proliferation of
      A549 carcinoma cells via blocking cell cycle progression and inducing apoptosis.
AB  - In this study, the antiproliferative activity of prodelphinidin B-2 3, 3'-di-O
      gallate (PB233'OG) isolated from the bark of Myrica rubra (Myricaceae) was
      investigated. The results showed that PB233'OG inhibited the proliferation of
      A549 by blocking cell cycle progression in the G0/G1 phase and inducing
      apoptosis. Enzyme-linked immunosorbent assay (ELISA) showed that the G0/G1 phase
      arrest is due to increase the expression of p21/WAF1. An enhancement in Fas/APO-1
      and its two form ligands, membrane-bound Fas ligand (mFasL) and soluble Fas
      ligand (sFasL), might be responsible for the apoptotic effect induced by
      PB233'OG. Our study reports here for the first time that the induction of
      p21/WAF1 and activity of the Fas/Fas ligand apoptotic system may participate in
      the anti-proliferative activity of PB233'OG in A549 cells.

PMID- 15464062
TI  - Functional pharmacology of human prostanoid EP2 and EP4 receptors.
AB  - Prostanoid EP(2) and EP(4) receptor-mediated responses are difficult to
      distinguish pharmacologically because of the lack of potent, selective
      antagonists. We describe systematic agonist fingerprints for recombinant human
      prostanoid EP(2) and EP(4) receptors expressed in CHO and HEK293 cells,
      respectively. The rank orders of potency of endogenous prostaglandins were:
      prostanoid EP(2) receptors: prostaglandin E(2)>>prostaglandin D(2)=prostaglandin
      F(2alpha)>prostaglandin I(2); prostanoid EP(4) receptors: prostaglandin
      E(2)>>prostaglandin I(2)>prostaglandin D(2)=prostaglandin F(2alpha). Butaprost
      free acid (9-oxo-11alpha,16R-dihydroxy-17-cyclobutyl-prost-13E-en-1-oic acid)
      behaved as a highly selective partial agonist at prostanoid EP(2) receptors while
      butaprost methyl ester elicited small, low potency responses. The prostanoid
      EP(1) and EP(3) receptor agonists misoprostol (9-oxo-11alpha,16-dihydroxy-16
      methyl-prost-13E-en-1-oic acid, methyl ester), sulprostone (N-(methylsulphonyl)-9
      oxo-11alpha,15R-dihydroxy-16-phenoxy-17,18,19,20-tetranor-prosta-5Z,13E-dien-1
      amide), and GR63799X ([1R-[1alpha(Z),2beta(R*),3alpha]-(-)-4-benzoylamino)phenyl
      7-[3-hydroxy-3-phenoxy-propoxy)-5-oxocyclopentyl]-4-heptenoate), and the
      prostanoid DP receptor agonist BW245C ((4S)-(3-[(3R,S)-3-cyclohexyl-3
      hydropropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid), activated both prostanoid
      EP(2) and EP(4) receptors. Prostaglandin I(2), iloprost (6,9alpha-methylene
      11alpha,15S-dihydroxy-16-methyl-prosta-5E,13E-dien-18-yn-1-oic acid, trometamol
      salt) and cicaprost (5-[(E)-(1S, 5S, 6S, 7R)-7-hydroxy-6-[(3S, 4S)-3-hydroxy-4
      methylnona-1,6-diinyl]-bicyclo[3.3.0]octan-3-yliden]-3-oxapentanoic acid;
      ZK96480) were full agonists at prostanoid EP(4) receptors. Key differentiating
      agonists are: butaprost FA, 16,16-dimethyl-prostaglandin E(2), 19-(R)-hydroxy
      prostaglandin E(2), misoprostol, BW245C, prostaglandin F(2alpha) and
      prostaglandin D(2).

PMID- 15464063
TI  - Comparative pharmacology of bovine, human and rat vasopressin receptor isoforms.
AB  - In this study, we characterized the bovine vasopressin V(1a), V(1b), V(2)
      receptor isoforms and compared their pharmacological properties to those of
      corresponding rat and human vasopressin receptor subtypes. Specific binding sites
      of high affinity for vasopressin were found in all bovine tissues tested (kidney,
      liver and pituitary). Using a large series of recent peptidic and non-peptidic
      selective vasopressin agonists or antagonists, we demonstrated the presence of
      vasopressin V(2), V(1a) or V(1b) receptors in the kidney, liver and pituitary
      bovine tissues, respectively. This extensive characterization of bovine
      vasopressin receptor isoforms validates the pharmacological vasopressin receptor
      classification earlier established for the rat and human species. As expected,
      the bovine vasopressin receptors look much more like human receptors than rat
      ones. Interestingly, among the three vasopressin receptor isoforms studied, the
      vasopressin V(1b) receptor subtype is the best conserved for the three species
      studied.

PMID- 15464064
TI  - Toosendanin, a triterpenoid derivative, acts as a novel agonist of L-type Ca2+
      channels in neonatal rat ventricular cells.
AB  - Toosendanin, a triterpenoid derivative extracted from Melia toosendan Sieb et
      Zucc, was demonstrated to be potentially useful in medical and scientific
      researches. Here, we investigated the effects of toosendanin on L-type voltage
      dependent Ca(2+) channels in cultured neonatal rat ventricular cells, using whole
      cell patch-clamp method. Toosendanin irreversibly increased L-type Ca(2+) current
      (I(Ca(L))) in a concentration-dependent manner and shifted the maximum of the
      current/voltage relationship from 8.3+/-3.7 to 1.7+/-3.7 mV, without modifying
      the threshold potential of the current. Toosendanin shifted the steady-state
      activation and inactivation curves to the left. The deactivation kinetics of the
      I(Ca(L)) was significantly slowed by toosendanin while the activation kinetics
      was not affected. The cells pretreated with 100 nM 1,4-dihydro-2,6-dimethyl-5
      nitro-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid methyl ester (S(-)
      BayK8644) still respond to further addition of 87 microM toosendanin, and vice
      versa. These results prove toosendanin to be a novel L-type Ca(2+) channel
      agonist, which possesses a distinct binding site from BayK8644.

PMID- 15464065
TI  - Involvement of adenosine A1 receptors in upregulation of nitric oxide by acyclic
      nucleotide analogues.
AB  - Acyclic nucleoside phosphonates are a novel class of virostatics effective
      against replication of both DNA-viruses and retroviruses. They are synthetic
      analogues of natural nucleotide monophosphates, and purine derivatives thus
      represent counterparts of AMP. Mono- and di-phosphorylated species are analogues
      of natural ADP and ATP, respectively. A number of these compounds are endowed
      with immunostimulatory and immunomodulatory potential. We investigated whether
      their augmenting effect on the interferon-gamma-primed production of nitric oxide
      (NO) by murine macrophages is mediated by purinoceptors. The test compounds
      comprise alterations at the N(6)-group of the heterocyclic base, i.e., adenine or
      2,6-diaminopurine, and at the N(9)-side chain, represented by 9-[2
      (phosphonomethoxy)ethyl] and 9-[2-(phosphonomethoxy)propyl] moieties: 9-[2
      (phosphonomethoxy)propyl]adenine [(R)-PMPA; tenofovir], N(6)-cyclopropyl-(R)-9-[2
      (phosphonomethoxy)propyl]2,6-diaminopurine [N(6)-cyclopropyl-(R)-PMPDAP], N(6)
      cyclopentyl-(R)-9-[2-(phosphonomethoxy)propyl]2,6-diaminopurine [N(6)-cyclopentyl
      (R)-PMPDAP], N(6)-dimethylaminoethyl-(R)-9-[2-(phosphonomethoxy)propyl]2,6
      diaminopurine [N(6)-dimethylaminoethyl-(R)-PMPDAP], N(6)-isobutyl-9-[2
      (phosphonomethoxy)ethyl]2,6-diaminopurine (N(6)-isobutyl-PMEDAP), N(6)
      cyclopentyl-9-[2-(phosphonomethoxy)ethyl]2,6-diaminopurine (N(6)-cyclopentyl
      PMEDAP), N(6)-cyclooctyl-9-[2-(phosphonomethoxy)ethyl]2,6-diaminopurine (N(6)
      cyclooctyl-PMEDAP), and N(6)-cyclohexylmethyl-9-[2-(phosphonomethoxy)ethyl]2,6
      diaminopurine (N(6)-cyclohexylmethyl-PMEDAP). The cells were cultured in the
      presence of interferon-gamma (5000 pg/ml) and test compounds (2-50 microM).
      Formation of nitrites was determined after 24 h using Griess reagent. It was
      inhibited by specific and nonspecific antagonists of adenosine A(1) receptors
      (IC(50) for 8-cyclopentyl-1,3-dipropylxanthine [CPX] was approximately 10
      microM), while all other purine P(1) and purine P(2) receptor antagonists
      remained ineffective to suppress the NO-synergistic effect of acyclic nucleoside
      phosphonates.

PMID- 15464066
TI  - Endothelins induce ETB receptor-mediated mechanical hypernociception in rat
      hindpaw: roles of cAMP and protein kinase C.
AB  - The present study assesses the capacity of endothelins to induce mechanical
      hypernociception, and characterises the receptors involved and the contribution
      of cAMP and protein kinases A (PKA) and C (PKC) to this effect. Intraplantar
      administration of endothelin-1, endothelin-2 or endothelin-3 (3-30 pmol) induced
      dose- and time-dependent mechanical hypernociception, which was inhibited by BQ
      788 (N-cys-2,6-dimethylpiperidinocarbonyl-l-gamma-methylleucyl-d-1-methoxycarboyl
      d-norleucine; endothelin ET(B) receptor antagonist), but not BQ-123 (cyclo[d-Trp
      d-Asp-Pro-d-Val-Leu]; endothelin ET(A) receptor antagonist; each at 30 pmol). The
      selective endothelin ET(B) receptor agonist BQ-3020 (N-Ac-Ala(11,15)-endothelin-1
      (6-21)) fully mimicked the hypernociceptive effects of the natural endothelins.
      Treatments with indomethacin, atenolol or dexamethasone did not inhibit
      endothelin-1-evoked mechanical hypernociception. However, endothelin-1-induced
      mechanical hypernociception was potentiated by the cAMP phosphodiesterase
      inhibitor rolipram (4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidinone) and
      inhibited by the PKC inhibitors staurosporine and calphostin C, but was
      unaffected by the PKA inhibitor H89 (N-[2-((p-bromocinnamyl)amino)ethyl]-5
      isoquinolinesulfonamide). Thus, endothelins, acting through endothelin ET(B)
      receptors, induce mechanical hypernociception in the rat hindpaw via cAMP
      formation and activation of the PKC-dependent phosphorylation cascade.

PMID- 15464067
TI  - Clonidine and guanfacine-induced antinociception in visceral pain: possible role
      of alpha 2/I2 binding sites.
AB  - Visceral pain is one of the most common forms of pain which is poorly understood.
      We now studied the influence of imidazoline/guanidinium compounds such as
      clonidine and guanfacine on visceral pain in the presence or absence of yohimbine
      and benazoline. To produce visceral pain-related behaviours, formalin (10%) was
      administered by inserting a fine cannula into the colon via the anus. Each
      experiment took 1 h. Clonidine (0.001, 0.01 and 0.1 mg/kg, i.p.) and guanfacine
      (2.5, 5 and 10 mg/kg, i.p.) produced analgesia dose dependently. The clonidine
      response was inhibited by yohimbine (0.2 mg/kg, i.p.). On the other hand,
      benazoline (5 mg/kg, i.p.) blocked the antinociceptive effect of guanfacine (5
      mg/kg). Benazoline (2.5 and 5 mg/kg) itself also induced analgesia in
      inflammatory colonic pain. In this study, we used morphine to ensure that the
      behavioural responses were pain-related. Our results showed that morphine (2.5, 5
      and 10 mg/kg, s.c.) produced a dose-dependent antinociception. The morphine (7
      mg/kg, s.c.) response was reduced by naloxone (2 mg/kg, i.p.). However, we
      concluded that both imidazoline (I(2)) and alpha(2)-adrenoceptors may play a role
      in producing analgesia in visceral pain.

PMID- 15464068
TI  - Long-term exposure of rats to tramadol alters brain dopamine and alpha 1
      adrenoceptor function that may be related to antidepressant potency.
AB  - The aim of the present study was to determine whether tramadol, which has a
      potential antidepressant efficacy, evokes, when administered repeatedly, changes
      similar to the alterations induced by conventional antidepressant drugs. Repeated
      administration of tramadol (20 mg/kg i.p. for 21 days) enhanced the d-amphetamine
      induced locomotor hyperactivity and increased the density of alpha(1)
      adrenoceptors in the rat brain cortex, as measured by saturation analysis of
      [(3)H]prazosin binding. Autoradiographic analysis of [(3)H]7-OH-DPAT and
      [(3)H]raclopride binding revealed a significant up-regulation of dopamine D2 and
      D3 receptors in the rat nucleus accumbens upon repeated treatment with tramadol.
      All the above-mentioned effects induced by repeated administration of tramadol
      resemble the effects induced by conventional antidepressants. However, tramadol
      when administered repeatedly did not increase the levels of mRNA encoding for
      brain-derived neurotrophic factor (BDNF) and its receptor, TrkB. This is what
      differs tramadol from conventional antidepressants, since neurotrophic effects of
      these drugs have recently been postulated.

PMID- 15464069
TI  - Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist.
AB  - Biological studies were conducted on (3R)-7-Hydroxy-N-[(1S)-1-[[(3R,4R)-4-(3
      hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2-methylpropyl]-1,2,3,4
      tetrahydro-3-isoquinoline-carboxamide (JDTic), the first potent kappa-selective
      opioid receptor antagonist not derived from an opiate class of compounds. In the
      mouse tail-flick test, JDTic, administered subcutaneously (s.c.), blocked
      anticociceptive activity for up to 2 weeks. When JDTic was administered either
      s.c. or p.o. 24 h before the selective KOP (kappa)-opioid receptor agonist,
      enadoline, AD(50s) of 4.1 and 27.3, respectively, were obtained. A time-course
      study of JDTic versus enadoline indicated significant antagonist p.o. activity up
      to 28 days. In contrast, JDTic, s.c., failed to antagonize the analgesic effects
      of the selective MOP mu-opioid receptor agonist, sufentanil. In the squirrel
      monkey shock titration antinociception test, JDTic given intramuscularly (i.m.)
      shifted the trans-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl)
      benzeneacetamide (U50,488) dose-effect curve to the right. In the U50,488-induced
      diuresis rat test, JDTic, s.c., suppressed diuretic activity with a greater
      potency than that of nor-binaltorphimine (nor-BNI). Thus, JDTic is a potent long-
      and orally acting selective kappa-opioid antagonist.

PMID- 15464070
TI  - Anxiolytic-like activity of MGS0039, a potent group II metabotropic glutamate
      receptor antagonist, in a marble-burying behavior test.
AB  - Glutamatergic abnormalities are involved in several psychiatric disorders.
      Clinical evidence demonstrates altered glutamatergic neurotransmission in
      patients suffering from obsessive-compulsive disorder. MGS0039, (1R,2R,3R,5R,6R)
      2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic
      acid, is a novel group II metabotropic glutamate (mGlu) receptor antagonist. We
      examined MGS0039's potential anti-obsessive-compulsive disorder activity, using
      the marble-burying behavior test as a model of obsessive-compulsive disorder.
      MGS0039 as well as LY341495 ((2S,1'S,2'S)-2-(9-xanthylmethyl)-2-(2'
      carboxycycloprolyl)glycine), another group II mGlu receptor antagonist, inhibited
      marble-burying behavior. We also demonstrated that this effect was significantly
      attenuated by a group II mGlu receptor agonist. This data indicates that group II
      mGlu receptor antagonists may exert anti-obsessive-compulsive disorder effects in
      clinical use.

PMID- 15464071
TI  - Arachidonic acid relaxes human pulmonary arteries through K+ channels and nitric
      oxide pathways.
AB  - We aimed to investigate the role of K(+) channels and nitric oxide (NO) on the
      relaxant effects of arachidonic acid in the human intralobar pulmonary arteries.
      Arachidonic acid produced a concentration-dependent relaxation (E(max)=93+/-3% of
      maximal relaxation induced by papaverine 0.1 mM;-log EC(30)=7.03+/-0.09) that was
      antagonized by the cyclooxygenase inhibitor indomethacin (1 microM), by the
      combination of cyclooxygenase blockade and cytochrome P450 (CYP) blockade with 17
      octadecynoic acid (17-ODYA, 10 microM), by the combination of cyclooxygenase
      inhibition and NO synthase (NOS) inhibition with N(omega)-nitro-l-arginine (l
      NOARG, 100 microM), by the simultaneous inhibition of CYP and NOS and by the
      simultaneous blockade of cyclooxygenase, CYP and NOS. Arachidonic acid-induced
      relaxation was significantly inhibited by glibenclamide (1 microM, ATP-dependent
      K(+) channel (K(ATP)) blocker), apamin and charybdotoxin (0.3 microM small
      (SK(Ca)) and 0.1 microM big (BK(Ca)) conductance Ca(2+)-sensitive K(+) channel
      blocker, respectively), and 4-aminopyridine (1 mM, voltage-dependent K(+) channel
      (K(V)) blocker). Indomethacin and ketoconazole suppressed the antagonistic
      effects of glibenclamide and apamin and 17-ODYA those of all the K(+) channel
      blockers tested. l-NOARG suppressed only the antagonistic effect of
      glibenclamide. We suggest that K(ATP), SK(Ca), BK(Ca) and K(V) are involved in
      the arachidonic acid-induced relaxation of human pulmonary arteries.
      Cyclooxygenase metabolites are the main relaxing agents of arachidonic acid,
      involving K(ATP) and SK(Ca) channels. CYP-dependent metabolites modulate
      arachidonic acid-induced relaxation through a pathway involving K(+) channels.
      K(ATP) channels are involved through a NOS-dependent pathway.

PMID- 15464072
TI  - A gastrointestinal lipase inhibitor reduces progression of atherosclerosis in
      mice fed a western-type diet.
AB  - To investigate whether gastrointestinal lipase inhibition reduces the progression
      of a western-type diet induced atherosclerosis, male apolipoprotein-E knockout
      (apoE KO) mice were administered orlistat ((S)-1-[[(S, 2S, 3S)-3-hexyl-4-oxo-2
      oxetanyl] methyl]dodecyl-(S)-2-formamido-4-methylvalerate) mixed with a western
      type diet for 8 weeks. Orlistat significantly reduced plasma triglyceride levels,
      but not total cholesterol levels, at 4 and 8 weeks of treatment. Increase in
      plasma triglyceride levels after oral olive oil loading in the mice fed a western
      type diet was significantly suppressed in the orlistat treated group at 4 weeks
      of treatment. After 8 weeks treatment, atherosclerotic lesion area in the aorta
      of the orlistat treated group was significantly smaller than that of the control
      group. These results suggest that gastrointestinal lipase inhibition reduces the
      progression of atherosclerosis through a triglyceride-lowering effect, via
      inhibition of fat absorption.

PMID- 15464073
TI  - Effect of cyclohexenonic long-chain fatty alcohol on rat overactive bladder
      induced by bladder neck obstruction.
AB  - We attempted to clarify the preventive effects of cyclohexenonic long-chain fatty
      alcohol on detrusor overactivity induced by mild bladder neck obstruction.
      Bladder neck obstruction was created by partial ligation of the urethra. Female
      Sprague-Dawley rats were divided into three groups: those with bladder neck
      obstruction treated without long-chain fatty alcohol, those with bladder neck
      obstruction with long-chain fatty alcohol (8 mg/kg, i.p., every day) and the sham
      operated control group (A, B, and C groups, respectively). Six weeks after the
      induction of bladder neck obstruction, voiding behavior was observed in the
      metabolic cage, and a cystometrogram was performed in the experimental animals.
      Furthermore, Hematoxylin and Eosin, Azan-Mallory, and Bodian stainings were
      performed in these bladders. Bladder weight, voiding behaviors and a cystometry
      indicated that rats in the A group showed detrusor overactivity, which was
      improved by treatment with long-chain fatty alcohol. The proportion of connective
      tissue and the density of bundles of neurofibers in the bladder of the A group
      was significantly less than that in the other bladders. Mild bladder neck
      obstruction induces detrusor overactivity, which is improved by treatment with
      long-chain fatty alcohol.

PMID- 15464074
TI  - Possible involvement of P-glycoprotein in renal excretion of pazufloxacin in
      rats.
AB  - The present study aims to investigate whether pazufloxacin, a new quinolone
      antimicrobial agent, is a substrate for P-glycoprotein in vitro, and whether it
      is excreted from kidney by P-glycoprotein and/or multidrug resistance-associated
      protein (Mrp2) in vivo. The in vitro experiments showed that the intracellular
      accumulation of pazufloxacin in adriamycin-resistant human chronic myelogenous
      leukemia cells (K562/ADR) overexpressing P-glycoprotein was significantly lower
      than that in human chronic myelogenous leukemia cells (K562/S) not expressing P
      glycoprotein. When rats received an intravenous injection of pazufloxacin in
      combination with or without cyclosporine, cyclosporine significantly delayed the
      disappearance of pazufloxacin from plasma and decreased the systemic clearance
      and volume of distribution at steady state of pazufloxacin to 50% and 70% of the
      corresponding control values, respectively. Renal handling experiments revealed
      that the renal clearance of pazufloxacin was 75% of that corresponding to the
      systemic clearance, suggesting that the main route of pazufloxacin elimination is
      the kidney. Cyclosporine significantly increased the steady-state concentration
      of pazufloxacin in plasma by decreasing the tubular secretion clearance and
      glomerular filtration rate. These results suggest the possibility that
      pazufloxacin is excreted into the urine via P-glycoprotein. No significant
      differences in the renal and tubular secretion clearances of pazufloxacin were
      observed between normal rats and Eisai hyperbilirubinemic rats (EHBR), which have
      a hereditary deficiency in Mrp2, indicating the lack of the involvement of Mrp2
      in the renal excretion of pazufloxacin. Sparfloxacin, a P-glycoprotein substrate,
      also significantly decreased the renal and tubular secretion clearances of
      pazufloxacin, suggesting that pazufloxacin and sparfloxacin share the same
      transporters, including P-glycoprotein. The present study at least suggests that
      pazufloxacin is excreted into the urine via P-glycoprotein and some active drug
      transporters other than Mrp2.

PMID- 15464075
TI  - Acute relaxation of mouse duodenum [correction of duodenun] by estrogens.
      Evidence for an estrogen receptor-independent modulation of muscle excitability.
AB  - 17-beta-Estradiol, the stereoisomer 17-alpha-estradiol and the synthetic estrogen
      diethylstilbestrol (DES), all caused a rapid (<3 min) dose-dependent reversible
      relaxation of mouse duodenal spontaneous activity, reduced basal tone and
      depressed the responses to CaCl(2) and KCl. The steroidal antiestrogen 7alpha-[9
      [(4,4,5,5,5,-pentafluoropenty)sulphinyl]nonyl]-estra-1,3,5(19)-triene-3,17beta
      diol (ICI182,780) failed to either mimic or prevent the effect of 17-beta
      estradiol. The effect of estrogens was unrelated to activation of nitric oxide
      (NO), mitogen-activated protein kinase (MAPK), protein kinase A (PKA), protein
      kinase G (PKG) or protein kinase C (PKC). Estrogen-induced relaxation was
      partially reversed by 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2
      (trifluoromethyl)phenyl]-pyridine-3-carboxilic acid methyl ester (BAY-K8644),
      depolarization, or by application of tetraethylammonium or 4-aminopyridine, but
      not by glibenclamide, apamin, charybdotoxin, paxilline or verruculogen. The
      effects of BAY-K8644 and K(+) channel blockers were synergistic, and allowed
      relaxed tissues to recover spontaneous activity and basal tone. We hypothesize
      that the rapid non-genomic spasmolytic effect of estrogens on mouse duodenal
      muscle might be triggered by an estrogen-receptor-independent mechanism likely
      involving activation of tetraethylamonium- and 4-aminopyridine-sensitive K(+)
      channels and inhibition of L-type Ca2(+) channels on the smooth muscle cells.

PMID- 15464076
TI  - The bronchodilators 8-iso-prostaglandin E2 and prostaglandin E2 induce K+ current
      suppression via thromboxane A2 receptors in porcine tracheal smooth muscle.
AB  - We examined relaxations and changes in K(+) current evoked by 8-iso-prostaglandin
      E(2) and prostaglandin E(2) in porcine tracheal smooth muscle. Both autacoids
      completely reversed cholinergic tone; blockade of thromboxane A(2) receptors had
      no effect on relaxations to either compound. 8-iso-prostaglandin E(2) and
      prostaglandin E(2) suppressed outward K(+) currents while the thromboxane A(2)
      receptor agonist U46619 (9, 11-dideoxy-9a,11a-methanoepoxy prostaglandin
      F(2alpha)) had no significant effect. During thromboxane A(2) receptor
      antagonism, however, 8-iso-prostaglandin E(2) markedly augmented K(+) currents
      while prostaglandin E(2) no longer suppressed K(+) currents, indicating that the
      inhibition of K(+) currents by both compounds was thromboxane A(2) receptor
      mediated. Furthermore, the observation that K(+) currents were augmented by 8-iso
      prostaglandin E(2) but not by prostaglandin E(2) suggests that the salutory
      effect is not exerted through a prostaglandin E receptor. Additionally, our
      observations argue against any causal role for K(+) current activation in
      mediating relaxations evoked by isoprostanes or by prostaglandin E(2). We
      conclude that 8-iso-prostaglandin E(2) relaxes porcine tracheal smooth muscle
      independent of K(+) current activity, and that 8-iso-prostaglandin E(2) may also
      act at a non-thromboxane A(2)/non-prostaglandin E receptor to augment K(+)
      currents.

PMID- 15464077
TI  - Reduced renal ClC-5 Cl- channel expression in spontaneously hypertensive rats
      with microalbuminuria.
AB  - Mutations in a renal-specific Cl(-) channel, ClC-5, result in low-molecular
      weight proteinuria. Herein we studied ClC-5 expression in the kidneys of
      spontaneously hypertensive rats (SHR) to identify possible causes of their
      increased urinary excretion of albumin. The amount of ClC-5 protein was
      significantly reduced in 3-month-old SHR as compared with normotensive
      Wistar/Kyoto (WKY) rats. The ClC-5 protein level was partially restored by short
      term administration of perindopril, an inhibitor of angiotensin-converting
      enzyme. Corresponding to the increase in ClC-5 expression, the albuminuria in SHR
      improved to the control level. These results implicate the ClC-5 Cl(-) channel
      reduction in the development of albuminuria in the early stage of essential
      hypertension.

PMID- 15464078
TI  - Enhanced ecto-apyrase activity of stimulated endothelial or mesangial cells is
      downregulated by glucocorticoids in vitro.
AB  - Endothelial as well as mesangial cells show enhanced activity of ecto-apyrase
      following pro-inflammatory stimulation in vitro. Since this ecto-enzyme appears
      to be able to regulate plasma hemopexin, which latter molecule plays a role in
      the pathogenesis of corticosteroid responsive nephrotic syndrome, the question
      was raised whether glucocorticoids are potentially able to downregulate ecto
      apyrase activity of these cells. Therefore, cell cultures of endothelial or
      mesangial were stimulated with or without lipopolysaccharide (10 ng/ml). Parallel
      cultures were supplemented with prednisolone with or without the glucocorticoid
      receptor antagonist mifepristone in various concentrations. After 24 h, cytospins
      were prepared and cytochemically stained for ecto-apyrase activity. mRNA for
      apyrase of these cells was detected using reverse transcription-polymerase chain
      reaction (RT-PCR). Apyrase activity of either cells or soluble apyrase (0.16 U/ml
      buffer) with or without supplementation of prednisolone were biochemically
      assayed for their phosphatase activity. The results show significantly decreased
      ecto-apyrase activity of lipopolysaccharide-stimulated cells after treatment with
      prednisolone as compared to non-prednisolone-treated cells. Preincubation with
      mifepristone did not inhibit the effect of prednisolone. Identical mRNA signals
      for apyrase were found in prednisolone and non-prednisolone-treated cells.
      Interestingly, soluble apyrase also showed a significant decrease of activity
      following preincubation with prednisolone. It is concluded that prednisolone is
      able to downregulate ecto-apyrase of stimulated endothelial or mesangial cells,
      which may potentially inhibit the conversion of hemopexin to its pro-inflammatory
      isoform. As blocking of the cytosolic glucocorticoid receptor showed no effect
      upon the prednisolone action, whereas prednisolone is able to affect soluble
      apyrase per se, it is felt that this particular action of prednisolone may (at
      least partly) be mediated through a non-genomic pathway.

PMID- 15464079
TI  - Anti-inflammatory drugs and tumor necrosis factor-alpha production from
      monocytes: role of transcription factor NF-kappa B and implication for rheumatoid
      arthritis therapy.
AB  - Inhibition of tumor necrosis factor-alpha (TNF-alpha) represents a relevant
      target in rheumatoid arthritis therapy. Besides inhibiting cyclooxygenase, anti
      inflammatory drugs can affect the activation of transcription factors. We
      investigated the ability of dexamethasone, indomethacin, and rofecoxib to
      modulate nuclear factor-kappaB (NF-kappaB) activation and TNF-alpha release from
      human monocytes challenged with lipopolysaccharide (LPS) or phorbol 12-myristate
      13-acetate (PMA). Both stimuli induced NF-kappaB nuclear translocation and TNF
      alpha secretion. Dexamethasone potently inhibited TNF-alpha release, indomethacin
      inhibited only PMA-evoked release, while rofecoxib had no effect. In the
      electrophoretic mobility shift assay, dexamethasone and rofecoxib dose
      dependently inhibited the DNA binding activity of NF-kappaB in stimulated
      monocytes, whereas indomethacin failed to inhibit the LPS-evoked one. These
      results were further confirmed by evaluating the drugs' ability to reduce nuclear
      NF-kappaB subunits, as well as the amount of phosphorylated IkappaBalpha in
      cytosolic fractions. In conclusion, these results indicate that anti-inflammatory
      drugs differ largely in their ability to inhibit NF-kappaB activity and/or TNF
      alpha release from human monocytes. These effects can be relevant to rheumatoid
      arthritis therapy.

PMID- 15464080
TI  - Involvement of guanylate cyclase and potassium channels on the delayed phase of
      mouse carrageenan-induced paw oedema.
AB  - Previous studies from this laboratory have shown that administration of nitric
      oxide (NO) donors reduces the early phase (which peaks at 4 h) of carrageenan
      induced paw oedema. The aim of this study was to investigate the influence of NO
      donors on the delayed phase of the mouse paw oedema, which peaks 48 h after
      carrageenan injection. Treatment of animals with sodium nitroprusside (1.5, 5 and
      10 micromol/kg, subcutaneously (s.c.)) 8 h after the subplantar carrageenan
      injection (300 microg/paw), reduced ( approximately 50%) the delayed phase of paw
      oedema and the delayed increase in plasma leakage, as assessed by Evans Blue
      extravasation. Two other NO donors, S-nitroso-N-acetyl-dl-penicillamine (SNAP) or
      glyceril trinitrate (both at 28 micromol/kg) yielded an inhibition in paw oedema
      similar to that of sodium nitroprusside. NO-induced inhibition of the delayed
      phase of paw oedema was reversed when animals were treated with 1H-[1,2,4]
      oxadiazolo-[4,3-a]quinoxalin-1 (ODQ, a soluble guanylate cyclase inhibitor, 11
      micromol/kg, s.c.) or with tetraethylammonium (TEA, a nonselective potassium
      channel blocker, 300 micromol/kg, s.c.), 30 min before the prophylactic dose of
      sodium nitroprusside. In conclusion, our results show that a brief exposure to NO
      donors, even when made several hours after the inflammatory reaction has been
      triggered, is still able to cause an important reduction on the delayed phase of
      carrageenan-induced mouse paw oedema and fluid leakage. Moreover, this long
      lasting NO antiinflammatory effect appears to be dependent on guanylate cyclase
      and potassium channels.

PMID- 15464081
TI  - Cyclosporine and bromocriptine-induced suppressions of CYP3A1/2 and CYP2C11 are
      not mediated by prolactin.
AB  - The purpose of this study was to determine if the suppression of hepatic CYP3A1/2
      (cytochrome P450 3A1/2) and CYP2C11 (cytochrome P450 2C11) by cyclosporine is
      mediated by prolactin. Male intact rats were given subcutaneous doses of either
      15 mg/kg/day of cyclosporine or 1 ml/kg/day of cyclosporine vehicle concomitantly
      with one of the following: 500 mg/kg prolactin, 1 ml/kg prolactin vehicle, 4
      mg/kg bromocriptine, or 1 ml/kg bromocriptine vehicle for 14 days. Protein
      expressions were measured using Western blot analysis and activities were
      measured using an in vitro testosterone hydroxylation assay. The administration
      of prolactin did not significantly alter CYP3A1/2 protein expression.
      Hypoprolactinemia, produced by bromocriptine, caused a significant suppression of
      CYP3A1/2 activity levels when bromocriptine was administered alone and in
      combination with cyclosporine (P<0.001, P<0.05; respectively). However, the cause
      of the suppression by bromocriptine was likely not the result of lowering
      prolactin levels. Bromocriptine administration also lowered CYP2C11 protein
      expression and activity, while prolactin administration had virtually no effect
      on CYP2C11. Chronic cyclosporine administration caused a 140% increase in
      prolactin area under the curve (AUC) (P<0.001). Bromocriptine caused a
      significant decline in endogenous prolactin secretion, however, concurrent
      cyclosporine administration did not recover these levels. Overall, while both
      cyclosporine and bromocriptine, separately, can significantly alter the fate of
      hepatic P450 enzymes, the suppression is likely not due to an alteration in
      prolactin levels.

PMID- 15464082
TI  - Hepatic glucagon receptor binding and glucose-lowering in vivo by peptidyl and
      non-peptidyl glucagon receptor antagonists.
AB  - Glucagon receptor antagonists have been actively pursued as potential
      therapeutics for the treatment of type 2 diabetes. Peptidyl and non-peptidyl
      glucagon receptor antagonists have been shown to block glucagon-induced blood
      glucose elevation in both animals and humans. How the antagonists and the
      glucagon receptor interact in vivo has not been reported and is the subject of
      the current study. Using (125)I-labeled glucagon as a radiotracer, we developed
      an in vivo glucagon receptor occupancy assay in mice expressing a human glucagon
      receptor in place of the endogenous mouse glucagon receptor (hGCGR mice). Using
      this assay, we first showed that the glucagon receptor is expressed predominantly
      in liver, to a much lesser extent in kidney, and is below detection in several
      other tissues/organs in the mice. We subsequently showed that, at 2 mg/kg body
      weight (mg/pk) dosed intraperitoneally (i.p.), peptidyl glucagon receptor
      antagonist des-His-glucagon binds to approximately 78% of the hepatic glucagon
      receptor and blocks an exogenous glucagon-induced blood glucose elevation in the
      mice. Finally, we also showed that, at 10 and 30 mg/kg dosed orally (p.o.),
      compound A, a non-peptidyl small molecule glucagon receptor antagonist, occupied
      65-70% of the hepatic glucagon receptor, and significantly diminished exogenous
      glucagon-induced blood glucose elevation in the mice. At 3 mg/kg, however,
      compound A occupied only approximately 39% of the hepatic glucagon receptor and
      did not affect exogenous glucagon-induced blood glucose elevation in the mice.
      Taken together, the results confirmed previous reports that glucagon receptors
      are present predominantly in the liver, and provide the first direct evidence
      that peptidyl and non-peptidyl glucagon receptor antagonists bind to the hepatic
      glucagon receptor in vivo, and that at least 60% receptor occupancy correlates
      with the glucose lowering efficacy by the antagonists in vivo.

PMID- 15464083
TI  - Cannabinoid receptor antagonist reduces heroin self-administration only in
      dependent rats.
AB  - Functionality of the endogenous cannabinoid system undergoes relevant changes in
      reward-related brain areas in animal models of opiate addiction. By using a
      limited access heroin self-administration paradigm we show that cannabinoid CB(1)
      receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)
      4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A, 0.03-3.0 mg/kg)
      suppresses heroin self-administration only in opiate-dependent rats but not in
      non-dependent animals. These results further support the study of cannabinoid
      CB(1) receptor antagonists for the treatment of opiate addiction.

PMID- 15464084
TI  - Antitumor activities of a novel indolin-2-ketone compound, Z24: more potent
      inhibition on bFGF-induced angiogenesis and bcl-2 over-expressing cancer cells.
AB  - The present study was designed to select the effective dosage range of Z24 [3Z-3
      [(1H-pyrrol-2-yl)-methylidene]-1-(1-piperidinylmethyl)-1,3-2H-indol-2-one], a
      novel synthetic indolin-2-ketone small-molecule compound, against tumorigenesis
      and angiogenesis in vitro and in vivo and to investigate the primary action
      mechanism of Z24 on the angiogenesis by comparing with SU5416 [3-[(2,4
      dimethylpyrrol-5-yl)methyllidenyl]-indolin-2-one] in the selective effects on
      vascular endothelial growth factor (VEGF)/basic fibroblast growth factor (bFGF)
      signaling and Bcl-2-related cell vitality because Z24 is a potential inhibitor of
      the Bcl-2 that inhibits growth of multiple tumor types in vivo in our previous
      study. Per os Z24 inhibited dose-dependently the mouse S180 xenograft tumor
      growth and angiogenesis in mouse subcutaneous (s.c.) Matrigel plugs in vivo. The
      maximum growth inhibitory rate was 56.1% by 80 mg/kg/day on S180 mouse sarcoma
      cells; however, the maximum inhibitory potency on angiogenesis in C57BL/6 mouse
      subcutaneous Matrigel plug model was 50 mg/kg/day. Z24 inhibited angiogenesis in
      chicken chorioallantoic membrane (CAM) and invasion and inhibited tube formation
      of endothelial cells in a dose-dependent manner. Compared with SU5416, the IC50
      (50% inhibition concentration) of Z24 on the proliferation of ECV-304 carcinoma
      cells induced by VEGF or bFGF was 24.4 and 17.99 microM, respectively, which is
      higher or lower, respectively, than that of SU5416 (14.2 microM for VEGF and 22.7
      microM for bFGF). Furthermore, the IC50 of Z24 on the proliferation of Bcl-2 over
      expressing HeLa cells and non-Bcl-2-expressing (wild-type) HeLa cells are 11.9
      and 24.8 microM, respectively. SU5416 did not exert such a selective inhibiting
      effect on Bcl-2 over-expressing HeLa cells. These results suggest that Z24 per os
      has dose-dependent antitumor and antiangiogenesis pharmacological activity. The
      higher selectivity of Z24 on Bcl-2 protein and on bFGF other than VEGF signaling
      path may contribute to its efficiency against tumor and tumor-associated
      angiogenesis.

PMID- 15464085
TI  - Desensitization of angiotensin-stimulated inositol phosphate accumulation in
      human vascular smooth muscle cells.
AB  - The effect of angiotensin II treatment on desensitization of phospholipase C
      (PLC)-mediated inositol phosphate accumulation has not been quantitated in human
      aortic vascular smooth muscle (HVSM) cells. We determined the angiotensin II
      pretreatment dose dependency and time course for desensitization of PLC
      activation in HVSM cells and the effect of protein kinase C (PKC) activators on
      angiotensin II-mediated inositol phosphate accumulation. Our results with PKC
      activators and direct G protein stimulators suggest that PKC activation may play
      a negative feedback role in desensitization of angiotensin II-activated signaling
      in HVSM cells by modifying the Gq transducer, PLC-beta effector, or related
      proteins in the signaling pathway. However, neither angiotensin II nor PKC
      activator affected basal phosphorylation levels of PLC-beta1 or PLC-beta3 in HVSM
      cells; PLC-beta isoenzymes were shown to be phosphorylated in unstimulated cells
      independent of PKC inhibition. We suggest that desensitization of G protein
      stimulated inositol phosphate accumulation in HVSM differs from other cell types
      in which phosphorylation of PLC-beta isoenzymes accompanies desensitization.

PMID- 15464086
TI  - Dose-dependent effect of dehydroepiandrosterone, but not of its sulphate ester,
      on angiogenesis.
AB  - Although dehydroepiandrosterone (DHEA) is widely used in the elderly to prevent
      some adverse effects of ageing, possible deleterious side effects have not been
      fully assessed. We evaluated the direct actions of DHEA and DHEA sulphate on
      angiogenesis, a critical event in pathologies that are common in the elderly
      (cancer, atherosclerosis, inflammation... etc.). At physiological concentrations
      found in human plasma following DHEA therapy (1-50 nM), DHEA had no action on
      angiogenesis in vitro. In contrast, higher concentrations of DHEA (10-100
      microM), which can be found in tissues after local administration or storage,
      inhibited in vitro endothelial cell proliferation (blockage in G2/M), migration
      and capillary tube formation and in vivo angiogenesis in the Matrigel plug assay.
      This inhibition might be due to a decreased glucose-6-phosphate dehydrogenase
      activity and to a modification of the tubulin network involved in cell
      proliferation and migration. The sulphate ester form of DHEA had no effect on
      angiogenesis.

PMID- 15464087
TI  - Stable expression and characterisation of a human alpha 7 nicotinic subunit
      chimera: a tool for functional high-throughput screening.
AB  - A chimera comprising the N-terminal region of the human alpha7 nicotinic
      acetylcholine receptor, fused to the transmembrane/C-terminal domains of the
      mouse serotonin 5-HT3 receptor, was constructed. Injection of the chimera cDNA
      into Xenopus oocytes, or transient transfection in human embryonic kidney (HEK
      293) cells, resulted in the expression of functional channels that were sensitive
      to nicotinic acetylcholine, but not serotonin receptor ligands. In both systems,
      the responses obtained from chimeric receptors inactivated more slowly than those
      recorded following activation of wild-type alpha7 receptors. A stable HEK-293
      cell line expressing the human alpha7/mouse 5-HT3 chimera was established, which
      showed that the chimera displayed a similar pharmacological profile to wild-type
      alpha7 receptors. Use of this chimera in high-throughput screening may enable the
      identification of novel pharmacological agents that will help to define further
      the role of alpha7 nicotinic receptors in physiology and disease.

PMID- 15464088
TI  - Apigenin modulates GABAergic and glutamatergic transmission in cultured cortical
      neurons.
AB  - Using the patch-clamp technique, we studied the modulation of ionotropic gamma
      aminobutyric acid (GABA) and glutamate neurotransmission by apigenin, a flavonoid
      with sedative and antidepressant activity. Apigenin reversibly reduced GABA
      evoked currents mediated by alpha1beta2gamma2 receptors expressed in HEK293
      cells. Amplitude and frequency of spontaneous postsynaptic inhibitory currents
      (sIPSCs) mediated by GABA(A) receptors were also decreased by apigenin in
      cultured cortical neurons. The flavonoid was almost inactive on alpha-amino-3
      hydroxy-5-methylisoxazolepropionic acid (AMPA) mediated currents while it reduced
      N-methyl-D-aspartate (NMDA) receptor mediated responses with a half maximal
      inhibiting concentration (IC50) of 10 microM. The flavonoid inhibited also peak
      amplitude and frequency of spontaneous postsynaptic excitatory currents (sEPSCs).
      Finally, apigenin is neuroprotective against glutamate-induced neurotoxicity in
      cerebellar and cortical neurons in culture. Our data reveal the antagonistic
      effect of apigenin on GABA and NMDA channels. While the inhibition on GABA
      receptor cannot explain the effects of the drug in vivo our data on NMDA channels
      reveal a new target of apigenin. A reduction of the network excitability could
      thus account for the sedative effects. Furthermore, our data suggest a potential
      neuroprotective activity of apigenin.

PMID- 15464089
TI  - Differential effects of endogenous and synthetic cannabinoids on voltage
      dependent calcium fluxes in rabbit T-tubule membranes: comparison with fatty
      acids.
AB  - The effects of cannabinoid receptor ligands including 2-arachidonoylglycerol, R
      methanandamide, Delta9-THC (Delta9-tetrahydrocannabinol), WIN 55,212-2 [4,5
      dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenylcarbonyl)-6H
      pyrrolo[3,2,1ij]quinolin-6-one], CP 55,940 ([1alpha,2beta-(R)-5alpha]-(-)-5-(1,1
      dimethyl)-2-[5-hydroxy-2-(3-hydroxypropyl) cyclohexyl-phenol]) and a series of
      fatty acids on depolarization-induced Ca2+ effluxes mediated by voltage-dependent
      Ca2+ channels were investigated comparatively in transverse tubule membrane
      vesicles from rabbit skeletal muscle. Vesicles were loaded with 45Ca2+ and
      membrane potentials were generated by establishing potassium gradients across the
      vesicle using the ionophore valinomycin. Endocannabinoids, 2-arachidonoylglycerol
      and R-methanandamide (all 10 microM), inhibited depolarization-induced Ca2+
      effluxes and specific binding of [3H]PN 200-110 (isradipine) to transverse tubule
      membranes. On the other hand, synthetic cannabinoids, including CP 55,940, WIN
      55,212-2, and Delta9-THC (all 10 microM), were ineffective. Additional
      experiments using endocannabinoid metabolites suggested that whereas ethanolamine
      and glycerol were ineffective, arachidonic acid inhibited Ca2+ effluxes and
      specific binding of [3H]PN 200-110. Further studies indicated that only those
      fatty acids containing two or more double bonds were effective in inhibiting
      depolarization-induced Ca2+ effluxes and specific binding of [3H]PN 200-110.
      These results indicate that endocannabinoids, but not synthetic cannabinoids,
      directly inhibit the function of voltage-dependent calcium channels (VDCCs) and
      modulate the specific binding of calcium channel ligands of the dihydropyridine
      (DHP) class.

PMID- 15464090
TI  - Biological evaluation of novel Pt(II) and Pd(II) complexes with pyrazole
      containing ligands.
AB  - The new platinum (II) and palladium (II) complexes (2-4) with ligands 5-(2
      hydroxyphenyl)-1,3-dimethyl-4-(dimethoxy)phosphonyl-1H]-pyrazole (1a) and 5-(2
      hydroxyphenyl)-1,3-dimethyl-4-methoxycarbonyl-1H]-2-pyrazole (1b) were screened
      in a search for novel anticancer agents. Thus, alkylating activity, cytotoxicity,
      ability for induction of apoptosis and binding to DNA were tested. The cis
      [Pt(1b)2Cl2] complex (3b) was the most potent alkylating agent in a Preussmann
      test, in comparison with the other test compounds and cis-platin. The highest
      cytotoxicity against the HL-60 and NALM-6 leukemia cell lines was observed for
      complexes 3b and 4b (trans-[Pd(1b)2Cl2]), although the extent of the effect was
      lower relative to cis-platin. Moreover, both complexes were remarkably less toxic
      to human umbilical vein endothelial cells (HUVECs) with IC50 values of 3b 14 and
      20 times higher than that ones for HL-60 and NALM-6 cells, respectively.
      Complexes 3b and 4b induced caspase-3 activity. Apoptosis occurred in a strictly
      dose-dependent manner and required only low concentrations of 4b. However,
      compounds 3b and 4b showed lower binding affinity to double-stranded DNA than cis
      platin.

PMID- 15464091
TI  - Dipyrone potentiates morphine-induced antinociception in dipyrone-treated and
      morphine-tolerant rats.
AB  - Coadministration of morphine and dipyrone produces acute and chronic
      antinociceptive potentiation in drug-naive rats. In this work, the effectiveness
      of the combination was determined in rats pretreated with morphine or dipyrone.
      Nine groups of male rats received (i.v.) 3.1 mg/kg morphine, 600 mg/kg dipyrone,
      or the morphine-dipyrone combination twice a day for five administrations (three
      groups per treatment). From the 6th to the 10th administration, one group out of
      each treatment continued without change, while the other two were switched to one
      of the other two possible treatments. In morphine-tolerant rats, morphine plus
      dipyrone produced a transient antinociceptive potentiation. In dipyrone-treated
      animals, this combination produced a long-lasting potentiation. In animals only
      treated with the combination, antinociception was clear since the beginning,
      although it decreased after the 6th injection. No cross-tolerance was seen
      between morphine and dipyrone. These data suggest that dipyrone potentiates
      morphine-induced antinociception in dipyrone-treated as well as in morphine
      tolerant rats.

PMID- 15464092
TI  - Neurochemical alterations produced by daily nicotine exposure in periadolescent
      vs. adult male rats.
AB  - Chronic treatment with nicotine differentially alters behavior in adolescent rats
      compared to adult rats. It is not known, however, whether the effects of nicotine
      on the neurochemical pathways with which it interacts differ in adolescents vs.
      adults. In the current study, the effects of a 7-day treatment with nicotine on
      nicotinic, dopaminergic, and serotonergic neurochemistry were examined in the
      caudate putamen and nucleus accumbens in periadolescent vs. adult male rats.
      Nicotine treatment increased dopamine transporter densities and decreased
      serotonin transporter densities in periadolescent rats. There was no change in
      nicotinic acetylcholine receptor densities or dopamine D1 or D2 receptor
      densities in nicotine-pretreated periadolescent rats. In adult rats pretreated
      with nicotine, there was an increase in nicotinic acetylcholine densities, but no
      change in dopamine transporter, dopamine D1 or D2 receptor, or serotonin
      transporter densities. Overall, these findings show that periadolescent rats have
      neurochemical adaptations to nicotine different from adult rats. These
      alterations may explain, at least in part, the differential behavioral effects of
      chronic nicotine in adult and adolescent male rats.

PMID- 15464093
TI  - Dexmedetomidine produces its neuroprotective effect via the alpha 2A-adrenoceptor
      subtype.
AB  - Which of the three alpha2-adrenoceptor subtypes of alpha2A, alpha2B, or alpha2C
      mediates the neuroprotective effect of dexmedetomidine was examined in cell
      culture as well as in an in vivo model of neonatal asphyxia. Dexmedetomidine dose
      dependently attenuated neuronal injury (IC50=83+/-1 nM) in neuronal-glial co
      cultures derived from wild-type mice; contrastingly, dexmedetomidine did not
      exert neuroprotection in injured cells from transgenic mice (D79N) expressing
      dysfunctional alpha2A-adrenoceptors. An alpha2A-adrenoceptor subtype-preferring
      antagonist 2-[(4,5-Dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H
      isoindole maleate (BRL44408) completely reversed dexmedetomidine-induced
      neuroprotection, while other subtype-preferring antagonists 2-[2-(4-(2
      Methoxyphenyl)piperazin-1-yl)ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione
      dihydrochloride (ARC239) (alpha2B) and rauwolscine (alpha2C) had no significant
      effect on the neuroprotective effect of dexmedetomidine in neuronal-glial co
      cultures. Dexmedetomidine also protected against exogenous glutamate induced cell
      death in pure cortical neuron cultures assessed by flow cytometry and reduced
      both apoptotic and necrotic types of cell death. Likewise this neuroprotective
      effect was antagonised by BRL44408 but not ARC239 or rauwolscine. Dexmedetomidine
      exhibited dose-dependent protection against brain matter loss in vivo
      (IC50=40.3+/-6.1 microg/kg) and improved the neurologic functional deficit
      induced by the hypoxic-ischemic insult. Protection by dexmedetomidine against
      hypoxic-ischemic-induced brain matter loss was reversed by the alpha2A
      adrenoceptor subtype-preferring antagonist BRL44408; neither ARC239 nor
      rauwolscine reversed the neuroprotective effect of dexmedetomidine in vivo. Our
      data suggest that the neuroprotective effect of dexmedetomidine is mediated by
      activation of the alpha2A adrenergic receptor subtype.

PMID- 15464094
TI  - The ATP-regulated K+-channel inhibitor HMR-1372 affects synaptic plasticity in
      hippocampal slices.
AB  - Long-term potentiation (LTP) and long-term depression of synaptic transmission in
      the hippocampus are widely studied models of learning and memory processes. The
      role of ATP-regulated K+ channels (K(ATP)+ channels), which are abundant in the
      brain, has not yet been studied in long-term potentiation or long-term
      depression. We investigated whether K(ATP)+ channel inhibition by the highly
      selective K(ATP)+-channel blocker 1-[[5-[2-(5-tert-butyl-o-anisamido)ethyl]-2
      methoxyphenyl]sulfonyl]-3-methylthiourea (HMR-1372), a novel putative class III
      antiarrhythmic, affects long-term potentiation or the long-term depression
      induced by 3,5-dihydroxyphenylglycine (30 microM) in submerged rat hippocampal
      slices. HMR-1372 (10 microM) did not affect basal synaptic transmission, paired
      pulse inhibition, long-term depression or long-term potentiation elicited by a
      weak (weak long-term potentiation) tetanus, but significantly amplified the long
      term efficacy of long-term potentiation elicited by a strong tetanus (strong long
      term potentiation). The K(ATP)+-channel inhibitor glibenclamide (20 microM) also
      ameliorated only strong long-term potentiation. Our data suggest that K(ATP)+
      channels are activated during or after induction of long-term potentiation and
      play a role in controlling synaptic excitability.

PMID- 15464095
TI  - The carbonic anhydrase inhibitor acetazolamide exerts antidystonic effects in the
      dt(sz) mutant hamster.
AB  - Previous studies suggested an involvement of gamma-aminobutyric acid (GABA)
      mediated excitation by an enhanced efflux of bicarbonate ions in addition to
      retarded development of GABAergic inhibition in the syndrome of dt(sz) mutant
      hamsters, a model of paroxysmal dyskinesia in which dystonic episodes occur in
      response to stress. Acetazolamide blocks bicarbonate regeneration in neurons and
      can thereby reduce GABA-mediating excitation without affecting GABA-mediated
      inhibition. In the present study, the effects of acetazolamide (15-60 mg/kg,
      i.p.) on severity of dystonia were therefore examined in dt(sz) hamsters.
      Acetazolamide significantly reduced the severity of dystonia at a dose of 60
      mg/kg. These data are in line with several case reports from patients with
      paroxysmal dystonia, suggesting that acetazolamide can be useful in the treatment
      of this movement disorder. The mechanism of the antidystonic efficacy of
      acetazolamide has to be examined by further studies.

PMID- 15464096
TI  - The effect of tryptophan depletion on the action of haloperidol in MK-801-treated
      rats.
AB  - We investigated the effect of tryptophan depletion (tryptophan-free mixture) on
      locomotor activity in an animal model of schizophrenia, induced by acute
      administration of 5R,10S-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten
      5,10-imine hydrogen maleate (MK-801), and the influence of the tryptophan-free
      mixture on the action of the typical antipsychotic haloperidol. Male rats were
      pre-treated with haloperidol 60 min after receiving the tryptophan-free mixture
      (or water). We measured total distance travelled in an open field during a 90-min
      period. Administration of the tryptophan-free mixture resulted in decreased
      levels of tryptophan, serotonin and its metabolite 5-hydroxyindolacetic acid in
      the frontal cortex. Serotonin depletion increased the total distance travelled by
      MK-801-treated rats, modified the inhibitory effect of haloperidol and normalized
      the locomotor activity pattern in the model of schizophrenia-like behaviour. The
      effect of the tryptophan-free mixture combined with the classical antipsychotic
      haloperidol in MK-801-treated rats indicates the possibly important role of the
      serotonergic system in the action of antipsychotics.

PMID- 15464097
TI  - Comparison of sensitivity of surrogate markers of drug-induced torsades de
      pointes in canine hearts.
AB  - Given a limited information regarding the difference of the sensitivity of
      surrogate markers of drug-induced torsades de pointes, including early
      afterdepolarization, ectopic beats, phase 3 repolarization and dispersion of
      ventricular repolarization, we simultaneously analyzed them in the halothane
      anesthetized canine model (n=5). A non-specific IKr channel blocker sparfloxacin,
      which has been known to induce torsades de pointes in animals and clinical
      patients, prolonged the repolarization process in a dose-related and reverse use
      dependent manner. No significant change was detected in any of the proarrhythmic
      markers except for the backward parallel shift of phase 3 repolarization in the
      cardiac cycle with the QT interval prolongation, which would be the most
      sensitive marker in predicting the potential arrhythmogenic property of
      sparfloxacin in the "non-remodeled" normal heart.

PMID- 15464098
TI  - Activation of iberiotoxin-sensitive, Ca2+-activated K+ channels of porcine
      isolated left anterior descending coronary artery by diosgenin.
AB  - The objective of this study was to determine the vasodilating effect of 3beta
      hydroxy-5-spirostene (diosgenin), a phytoestrogen found in wild yams, using
      porcine resistance left anterior descending coronary artery. In 5
      hydroxytryptamine (3 microM) pre-contracted preparation, diosgenin caused a
      concentration-dependent (0.01 to 1 microM), endothelium-independent relaxation,
      with a maximum relaxation of approximately 72% at 1 microM. No apparent effect
      was observed with 17beta-oestradiol and progesterone with concentrations < or
      =0.3 microM, and a relaxation of approximately 15% and approximately 23% caused
      by 17beta-oestradiol (1 microM) and progesterone (1 microM), respectively.
      Diosgenin-elicited relaxation was not altered by 7alpha,17beta-[9[(4,4,5,5,5
      pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol (ICI 182,780),
      mifepristone, (+)-bicuculline, cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2
      amine (MDL 12330A), glibenclamide and scavengers of reactive oxygen species. The
      iberiotoxin-sensitive, Ca2+-activated K+ (BK(Ca)) current of single vascular
      myocytes recorded, using patch-clamp techniques, was markedly enhanced by
      diosgenin, 17beta-oestradiol and progesterone. Application of (9S, 10R, 12R)
      2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H
      diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic
      acid methyl ester (KT 5823, 300 nM) eradicated the enhancement of BK(Ca)
      amplitude. Diosgenin, 17beta-oestradiol and progesterone did not affect whereas
      phloretin, biochanin A and zearalanone (1 microM each) significantly suppressed
      [Ca2+]o-induced contraction. In oestrogen competition essay using human breast
      cancer cell (MCF-7 cells), diosgenin (0.001 nM to 10 microM) did not interact
      with oestrogen receptor-alpha, and no displacement of [3H]17beta-oestradiol was
      observed. In oestrogen receptor alpha- and beta-fluorescence polarization
      competitor assay, diosgenin (100 microM) demonstrated a greater competition with
      the beta-isoform of oestrogen receptor. These results suggest that diosgenin
      caused an acute, endothelium-independent coronary artery relaxation via protein
      kinase G signalling cascade and an activation of BK(Ca) channel of arterial
      smooth muscle cells. The oestrogen receptor (alpha and beta-isoforms) and
      progesterone receptor are probably not involved.

PMID- 15464099
TI  - Delayed preconditioning by cardiac ischemia involves endogenous calcitonin gene
      related peptide via the nitric oxide pathway.
AB  - Previous investigations have shown separately that calcitonin gene-related
      peptide (CGRP) or nitric oxide (NO) is involved in mediation of ischemic
      preconditioning. In the present study, we tested interactions of CGRP with NO in
      mediation of delayed preconditioning. In Sprague-Dawley rats, ischemia
      reperfusion injury was induced by 45-min occlusion followed by 3-h reperfusion of
      coronary artery, and preconditioning was induced by four cycles of 3-min ischemia
      and 5-min reperfusion. Infarct size, plasma creatine kinase activity, the plasma
      level of NO and CGRP, and the expression of CGRP mRNA in dorsal root ganglion
      were measured. Pretreatment with preconditioning significantly reduced infarct
      size and the release of creatine kinase during reperfusion, and caused a
      significant increase in the expression of CGRP mRNA, concomitantly with an
      elevation in the plasma level of CGRP and NO. The effects of preconditioning were
      completely abolished by administration of L-nitroarginine methyl ester (L-NAME,
      10 mg/kg, i.p.), an inhibitor of NO synthase. Pretreatment with capsaicin (50
      mg/kg, s.c.), which depletes transmitters in capsaicin-sensitive sensory nerves,
      also blocked the cardioprotection of preconditioning and reduced the synthesis
      and release of CGRP, but did not affect the concentration of NO. The present
      results suggest the delayed protection afforded by ischemic preconditioning is
      also mediated by endogenous CGRP via the NO pathway in rat heart.

PMID- 15464100
TI  - Effects of the peroxynitrite decomposition catalyst, FeTMPyP, on function of
      corpus cavernosum from diabetic mice.
AB  - Peroxynitrite, the reaction product of nitric oxide and superoxide, may
      contribute to vascular tissue oxidant stress in diabetes mellitus. The aim was to
      establish whether the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(N
      methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) could improve nitric oxide
      dependent autonomic nerve and microvascular penile function in the diabetic
      mouse. Diabetes was induced by streptozotocin; duration was 6 weeks. Intervention
      FeTMPyP treatment (25 mg kg(-1) day(-1)) was given for 2 weeks following 4 weeks
      untreated diabetes. Corpus cavernosum were isolated in organ baths for
      measurement of agonist or electrical stimulation-evoked nerve-mediated tension
      responses. Maximum nitrergic nerve-mediated relaxation of phenylephrine
      precontracted cavernosum was approximately 35% reduced by diabetes; FeTMPyP
      treatment reversed this deficit by 45%. The concentration response-curve for
      nitric oxide-mediated endothelium-dependent relaxation to acetylcholine was
      attenuated by diabetes; FeTMPyP restored the deficit to the nondiabetic range.
      Sensitivity (EC50) to the nitric oxide donor, sodium nitroprusside, was reduced
      by approximately 0.56 log10 M units in diabetes; however, FeTMPyP treatment
      failed to significantly reverse this deficit. Therefore, the peroxynitrite
      mechanism contributes to nitric oxide-dependent diabetic autonomic neuropathy and
      vasculopathy and may be a potential target for clinical trials using
      peroxynitrite decomposition catalysts.

PMID- 15464101
TI  - Segment-selective absorption of lysozyme in the intestine.
AB  - Absorption of fluorescein isothiocyanate-labeled lysozyme (FITC-lysozyme) was
      examined in rat small intestine. Messenger RNA of megalin, an endocytic receptor
      for lysozyme in the kidney, was expressed in the lower but not in the upper
      intestine. In in situ closed loop and recirculation methods, absorption of FITC
      lysozyme from the upper intestine was much higher than from the lower intestine.
      The absorption rate of FITC-lysozyme in the upper intestine was significantly
      higher than FITC-dextran and was inhibited by unlabeled lysozyme in a
      concentration-dependent manner. The absorption of FITC-lysozyme was also
      inhibited by spermine and phenylarsine oxide. These results indicate that the
      intestinal absorption of lysozyme is segment-selective and occurs preferentially
      from the upper intestine. Megalin expressed in the lower intestine appears not to
      have a significant role in the absorption of lysozyme. In the upper intestine,
      lysozyme appears to be absorbed by an endocytic pathway, and cationic charge may
      be important for lysozyme absorption.

PMID- 15464103
TI  - Trends in tobacco use.
AB  - The use of tobacco can be traced back to ancient times. Its popularity grew
      exponentially during the twentieth century, surging during wartime and with the
      advent of mass media. The tobacco industry in the United States has been under
      constant legal pressure during the past 40 years. Despite the well-known and
      continually increasing morbidity and mortality related to smoking, it continues
      to be a prominent feature in worldwide culture and health.

PMID- 15464104
TI  - Metabolism and biochemical effects of nicotine for primary care providers.
AB  - Nicotine is a colorless and volatile liquid alkaloid naturally occurring in the
      leaves and stems of Nicotiana tabacum and Nicotiana rustica. Nicotine, the
      primary component of tobacco, is responsible for both tobacco product addiction
      (with chronic exposure) and the odor associated with tobacco. In addition to
      cigarettes, nicotine is found in chewing gum, transdermal patches, nasal spray,
      and sublingual tablets. Following its inhalation and absorption, nicotine and its
      metabolic products exert diverse physiologic and pharmacologic effects. This
      article covers the absorption and metabolism of nicotine, nicotine toxicity,
      pharmacologic effects of nicotine, nicotine-drug interactions, and the use of
      nicotine for the treatment of disease.

PMID- 15464105
TI  - Pulmonary and cardiovascular consequences of smoking.
AB  - The extensive worldwide disease burden attributable to tobacco smoking is
      reviewed, with particular attention to the epidemiologic and clinical aspects,
      molecular and cellular mechanisms, and pathophysiology of a variety of smoking
      related pulmonary diseases, and the epidemiology and clinical presentation of
      smoking-related atherosclerotic disease as it affects the cardiovascular system
      cerebral circulation, the aorta, and the peripheral arterial tree.

PMID- 15464106
TI  - Smoking and systemic disease.
AB  - Cigarette smoking is associated with a number of adverse health effects,
      including well-established links to cardiopulmonary disease and several cancers.
      Some of the other important systemic diseases associated with smoking are the
      subjects of this article, such as diabetes mellitus and insulin resistance and
      thyroid diseases. Also reviewed here is the negative impact of smoking on male
      and female infertility, on selected dermatologic conditions, and on
      gastrointestinal diseases including peptic ulcer and inflammatory bowel diseases.

PMID- 15464107
TI  - Cigarette smoking and nicotine dependence.
AB  - Tobacco use is the single most preventable cause of death, disability, and
      disease in the United States and is projected to be the leading cause of death
      and disability across all developed countries by the year 2020. Understanding
      nicotine dependence, its causes, consequences, and effective treatments is
      critical to the nation's public health agenda. This article presents a brief
      overview of nicotine dependence with particular emphasis placed on understanding
      what nicotine dependence is, why it occurs, how it is measured, and how it can be
      managed through effective treatments.

PMID- 15464108
TI  - Women and tobacco dependence.
AB  - Millions of American girls and women have been drawn to smoking by an industry
      that has been clearly and systematically targeting women of all ages and life
      circumstances. Tobacco marketing strategies skillfully link cigarette use to
      typical female values. Biologically speaking, women are especially vulnerable to
      the legion of health problems of tobacco use. Smoking is a critical hazard for
      women in their reproductive years, particularly when they are pregnant.

PMID- 15464109
TI  - Smoking and depression.
AB  - The relationship between smoking and depression is bidirectional. Recent research
      has focused on nicotine's neurobiologic impact on the brain as it relates to
      depression. Genetic factors are also important and may account for up to 67% of
      smoking initiation, maintenance, and dependence. Because nicotine withdrawal may
      mimic and induce depression, appropriate clinical evaluation and treatment are
      essential to reduce the high morbidity and mortality associated with smoking and
      depression and maximize smoking cessation rates.

PMID- 15464110
TI  - Smoking in adolescence: what a clinician can do to help.
AB  - Approximately 4400 adolescents try their first cigarette every day in the United
      States. Trying a few cigarettes or using tobacco more regularly as an adolescent
      significantly increases the risk of smoking in adulthood. Adolescents can develop
      nicotine dependency after smoking relatively few cigarettes. This article points
      out the prevalence and unique aspects of teenage tobacco use. In addition,
      current recommendations for treating nicotine dependence in adolescents are
      reviewed.

PMID- 15464111
TI  - Pharmacotherapy of tobacco dependence.
AB  - Smoking cessation activities and support for its implementation should be
      integrated into the health care system. The outcome of smoking cessation has
      improved with the availability of proper behavior approaches and medications.
      Incorporating these guidelines into daily clinical practice ensures that health
      care providers provide the opportunity for patients to quit smoking. The best
      hope of improved treatment comes from combining existing and new
      pharmacotherapies with effective behavioral therapy.

PMID- 15464112
TI  - Respiratory health consequences of environmental tobacco smoke.
AB  - Over the last several decades there has been a growing interest in examining the
      health consequences of environmental tobacco smoke (ETS). As a result of a wide
      body of research, ETS is now considered an unacceptable and entirely preventable
      public health hazard, and public policy increasingly discourages the presence of
      tobacco smoke in the public domain. This article provides an overview of the
      composition of ETS and the major diseases and disorders strongly linked to ETS,
      emphasizing the effects of ETS on pulmonary function, asthma, and lung cancer.

PMID- 15464113
TI  - Promoting tobacco cessation and relapse prevention.
AB  - Although there is no single cure for tobacco dependence, there are numerous
      effective treatments for promoting cessation. Using the chronic disease model of
      advising and counseling, this article outlines a model for helping patients
      overcome tobacco dependence. This model consists of the five A's: Ask, Advise,
      Assess, Assist, and Arrange. Although most of this article focuses on how
      clinicians who are bound by time constraints can be effective in promoting
      tobacco cessation, key elements for more intensive interventions are briefly
      discussed and suggestions for dealing with the less motivated patient are
      offered.

PMID- 15464114
TI  - Smoking and sleep disorders.
AB  - Cigarette smoking is the most important cause of preventable disease, disability,
      and premature death in the United States. In addition to adverse effects on
      respiratory, cardiovascular, cerebrovascular, and other systems, accumulating
      evidence indicates that cigarette smoking may also increase morbidity by
      adversely affecting sleep. This article focuses on the effects of cigarette
      smoking, nicotine, and pharmacologic agents used for smoking cessation on
      neuronal systems regulating sleep and clinically apparent sleep disorders.

PMID- 15464115
TI  - Smokeless tobacco: an emerging addiction.
AB  - Smokeless tobacco (ST) use is an important health issue in the United States, and
      chronic use leads to significant morbidity. ST users are exposed to levels of
      nicotine comparable with smokers and experience symptoms of nicotine withdrawal
      when attempting to stop. Clinical treatment of ST users requires an understanding
      of the unique characteristics of ST. This article reviews ST products,
      epidemiology, pharmacology, health risks, and treatment approaches.

PMID- 15464116
TI  - Alternative therapies for tobacco dependence.
AB  - For both hypnotherapy and acupuncture, the evidence of any effect is anecdotal.
      There are insufficient rigorous studies that are homogeneous in design or results
      to allow a reliable conclusion on whether or not these therapies are effective.
      At best, individual smokers who choose one of these interventions for preference
      should not be discouraged provided that they are informed about the state of the
      evidence.

PMID- 15464117
TI  - Office-based intervention for tobacco dependence.
AB  - A successful office approach for any behavior change, including for tobacco,
      makes the intervention part of the everyday work of the medical practice. This
      article recommends how to integrate tobacco treatments efficiently into clinical
      practice. Specific ways to think systematically about smoking cessation and
      intervene with patients are discussed. Strategies to implement office-based
      changes to improve tobacco intervention are then presented.

PMID- 15464118
TI  - Cigarette smoking in interstitial lung disease: concepts for the internist.
AB  - Cigarette smoking is a common cause of lung disease. It is clearly implicated in
      the development of chronic obstructive pulmonary disease and lung cancer.
      Importantly, cigarette smoking has also been implicated in the development of
      interstitial lung diseases such as respiratory bronchiolitis interstitial lung
      disease, desquamative interstitial pneumonia, pulmonary Langerhans' cell
      histiocytosis,and idiopathic pulmonary fibrosis. The exact role of cigarette
      smoking in the development of interstitial lung diseases is still being defined;
      the relatively low prevalence of interstitial lung disease makes epidemiologic
      studies difficult.

PMID- 15464119
TI  - Overview of smoking and all cancers.
AB  - Tobacco consumption has been clearly implicated in the causation of many cancer
      types, with irrefutable evidence to support the association in multiple organ
      systems. Tobacco cessation leads to reduced cancer risk and improved survival of
      those under treatment for their already established cancers. As understanding of
      the mechanisms by which tobacco products cause cancer increases, clinicians may
      be able to identify those at highest risk for tobacco-related malignancies and
      allow for more focused interventions toward risk reduction among current tobacco
      users. This article reviews the carcinogens present in tobacco products, the
      mechanisms by which tobacco causes cancer, and the various tumor types causally
      related to tobacco use.

PMID- 15464121
TI  - The addicted human brain viewed in the light of imaging studies: brain circuits
      and treatment strategies.
AB  - Imaging studies have provided evidence of how the human brain changes as an
      individual becomes addicted. Here, we integrate the findings from imaging studies
      to propose a model of drug addiction. The process of addiction is initiated in
      part by the fast and high increases in DA induced by drugs of abuse. We
      hypothesize that this supraphysiological effect of drugs trigger a series of
      adaptations in neuronal circuits involved in saliency/reward, motivation/drive,
      memory/conditioning, and control/disinhibition, resulting in an enhanced (and
      long lasting) saliency value for the drug and its associated cues at the expense
      of decreased sensitivity for salient events of everyday life (including natural
      reinforcers). Although acute drug intake increases DA neurotransmission, chronic
      drug consumption results in a marked decrease in DA activity, associated with,
      among others, dysregulation of the orbitofrontal cortex (region involved with
      salience attribution) and cingulate gyrus (region involved with inhibitory
      control). The ensuing increase in motivational drive for the drug, strengthened
      by conditioned responses and the decrease in inhibitory control favors emergence
      of compulsive drug taking. This view of how drugs of abuse affect the brain
      suggests strategies for intervention, which might include: (a) those that will
      decrease the reward value of the drug of choice; (b) interventions to increase
      the saliency value of non-drug reinforcers; (c) approaches to weaken conditioned
      drug behaviors; and (d) methods to strengthen frontal inhibitory and executive
      control. Though this model focuses mostly on findings from PET studies of the
      brain DA system it is evident that other neurotransmitters are involved and that
      a better understanding of their roles in addiction would expand the options for
      therapeutic targets.

PMID- 15464122
TI  - The role of DARPP-32 in the actions of drugs of abuse.
AB  - The dopamine- and cAMP-regulated phosphoprotein, M(r) 32 kDa (DARPP-32), plays a
      key role in dopaminoceptive neurons in the neostriatum (and likely in other brain
      regions) in signal transduction pathways regulated by a variety of
      neurotransmitters, neuromodulators, and neuropeptides. Phosphorylation at Thr34
      by protein kinase A converts DARPP-32 into a potent inhibitor of the
      multifunctional serine/threonine protein phosphatase, PP-1. Phosphorylation at
      Thr75 by Cdk5 converts DARPP-32 into an inhibitor of protein kinase A. The state
      of phosphorylation of DARPP-32 at Thr34 also depends on the phosphorylation state
      of Ser102 and Ser137, which are phosphorylated by CK2 and CK1, respectively. By
      virtue of its regulation of its four phosphorylation sites by a large number of
      physiological and pharmacological stimuli, and through its ability to modulate
      the activity of PP-1 and protein kinase A, DARPP-32 plays a key role in
      integrating a variety of electrophysiological, transcriptional, and behavioral
      responses. This review focuses on the critical role that DARPP-32 plays in
      mediating the actions of a broad range of drugs of abuse.

PMID- 15464123
TI  - Molecular mechanisms of drug addiction.
AB  - Regulation of gene expression is one mechanism by which drugs of abuse can induce
      relatively long-lasting changes in the brain to cause a state of addiction. Here,
      we focus on two transcription factors, CREB (cAMP response element binding
      protein) and DeltaFosB, which contribute to drug-induced changes in gene
      expression. Both are activated in the nucleus accumbens, a major brain reward
      region, but mediate different aspects of the addicted state. CREB mediates a form
      of tolerance and dependence, which dampens an individual's sensitivity to
      subsequent drug exposure and contributes to a negative emotional state during
      early phases of withdrawal. In contrast, DeltaFosB mediates a state of relatively
      prolonged sensitization to drug exposure and may contribute to the increased
      drive and motivation for drug, which is a core symptom of addictive disorders. A
      major goal of current research is to identify the many target genes through which
      CREB and DeltaFosB mediate these behavioral states. In addition, future work
      needs to understand how CREB and DeltaFosB, acting in concert with numerous other
      drug-induced molecular changes in nucleus accumbens and many other brain regions,
      interact with one another to produce the complex behavioral phenotype that
      defines addiction.

PMID- 15464124
TI  - Structural plasticity associated with exposure to drugs of abuse.
AB  - Persistent changes in behavior and psychological function that occur as a
      function of experience, such those associated with learning and memory, are
      thought to be due to the reorganization of synaptic connections (structural
      plasticity) in relevant brain circuits. Some of the most compelling examples of
      experience-dependent changes in behavior and psychological function, changes that
      can last a lifetime, are those that accrue with the development of addictions.
      However, until recently, there has been almost no research on whether potentially
      addictive drugs produce forms of structural plasticity similar to those
      associated with other forms of experience-dependent plasticity. In this paper we
      summarize evidence that, indeed, exposure to amphetamine, cocaine, nicotine or
      morphine produces persistent changes in the structure of dendrites and dendritic
      spines on cells in brain regions involved in incentive motivation and reward
      (such as the nucleus accumbens), and judgment and the inhibitory control of
      behavior (such as the prefrontal cortex). It is suggested that structural
      plasticity associated with exposure to drugs of abuse reflects a reorganization
      of patterns of synaptic connectivity in these neural systems, a reorganization
      that alters their operation, thus contributing to some of the persistent sequela
      associated with drug use--including addiction.

PMID- 15464125
TI  - Understanding the neurobiological consequences of early exposure to psychotropic
      drugs: linking behavior with molecules.
AB  - Children receive significant exposure to psychotropic drugs. Some psychiatric
      disorders are diagnosed and treated in children as young as 2 years old,
      resulting in exposure to prescription stimulants, antidepressants, and mood
      stabilizers during brain development. Difficulties in diagnoses at such young
      ages increase the likelihood that children who are not affected by these
      disorders receive drug exposure inadvertently. Additionally, the increased
      availability of caffeine-containing beverages in schools has facilitated exposure
      to this stimulant in children. However, the consequences of exposure to
      psychotropic drugs during brain development are not understood. When we exposed
      rats to the prescription stimulant methylphenidate during early adolescence, we
      discovered long-lasting behavioral and molecular alterations that were consistent
      with dramatic changes in the function of brain reward systems. In future work, it
      will be important to determine if other classes of psychotropic drugs cause these
      same effects, and whether these effects will also occur if drug exposure begins
      during other periods of development. Moreover, it will be critical to use more
      powerful behavioral methods that are sensitive to high-level aspects of
      motivation and cognitive function, and to establish causal links between
      developmental exposure-related alterations in these complex behaviors and
      specific alterations in the molecular biology of key brain regions. This approach
      may identify classes of psychotropic drugs that have high or low propensities to
      cause behavioral and molecular adaptations that endure into adulthood. It may
      also identify periods of development during which administration of these agents
      is particularly safe or risky.

PMID- 15464126
TI  - Psychomotor stimulants and neuronal plasticity.
AB  - Considerable evidence suggests that neuroadaptations leading to addiction involve
      the same glutamate-dependent cellular mechanisms that enable learning and memory.
      Long-term potentiation (LTP) and long-term depression (LTD) have therefore become
      an important focus of addiction research. This article reviews: (1) basic
      mechanisms underlying LTP and LTD, (2) the properties of LTP and LTD in ventral
      tegmental area, nucleus accumbens, dorsal striatum and prefrontal cortex, (3)
      studies demonstrating that psychomotor stimulants influence LTP or LTD in these
      brain regions. In addition, we discuss our recent work on cellular mechanisms by
      which dopamine may influence LTP and LTD. Based on evidence that AMPA receptors
      are inserted into synapses during LTP and removed during LTD, we investigated the
      effects of D1 receptor stimulation on AMPA receptor trafficking using primary
      cultures prepared from nucleus accumbens and prefrontal cortex. Our results
      suggest that activation of the D1 receptor-protein kinase A signaling pathway
      leads to externalization of AMPA receptors and promotes LTP. This provides a
      mechanism to explain facilitation of reward-related learning by dopamine. When
      this mechanism is activated in an unregulated manner by psychostimulants,
      maladaptive forms of neuroplasticity may occur that contribute to the transition
      from casual to compulsive drug use.

PMID- 15464127
TI  - Rapid regulation of the dopamine transporter: role in stimulant addiction?
AB  - Dopamine (DA) and the DA transporter (DAT) play important roles in psychomotor
      stimulant behavioral activation and reward. By understanding how DAT activity is
      regulated, we will better appreciate its contribution to normal neurotransmission
      and to brain diseases like drug addiction. DAT is regulated long-term by chronic
      drug administration. It is also regulated in a rapid, dynamic fashion by many
      factors--including brief exposure to DAT substrates, e.g. DA and amphetamine, and
      inhibitors, e.g. cocaine. We found that individual differences in the initial and
      sensitized locomotor responsiveness of rats to cocaine reflect differences in in
      vivo DAT function. Our ex vivo studies have further suggested that differences in
      basal and/or rapid cocaine-induced expression of functional DATs in striatum
      contribute to the differences in initial responsiveness. Studies in model systems
      have demonstrated that short-term DAT regulation occurs by altered transporter
      trafficking, and thereby cell surface expression. For example, a rapid, complex
      regulation of DAT by DA is suggested. Amphetamine causes DAT internalization into
      early endosomal compartments whereas cocaine appears to up-regulate surface
      expression of DAT. Future studies are needed to confirm these observations in
      neurons, as well as to elucidate the mechanisms of rapid DAT endocytic
      trafficking at neuronal synapses.

PMID- 15464128
TI  - The methamphetamine experience: a NIDA partnership.
AB  - The neurotoxic properties of the amphetamines such as methamphetamine (METH) were
      originally described about the time of the National Institute on Drug Abuse's
      organization, in the early 1970s. It required more than 20 years to confirm these
      neurotoxic properties in humans. Much like Parkinson's disease, multiple high
      dose administration of METH somewhat selectively damages the nigrostriatal
      dopamine (DA) projection of the brain. This effect appears to be related to the
      intracellular accumulation of cytosolic DA and its ability to oxidize into
      reactive oxygen species. Both the dopamine plasmalemmal transporter and the
      vesicular monoamine transporter-2 seem to play critical roles in this
      neurotoxicity. METH and related analogs such as methylenedioxymethamphetamine
      (MDMA) can also damage selective CNS serotonin neurons. The mechanism of the
      serotonergic neurotoxicity is not as well characterized, but also appears to be
      related to the formation of reactive oxygen species and monoamine transporters.
      Studies examining the pharmacological and neurotoxicological properties of the
      amphetamines have helped to elucidate some critical features of monoamine
      regulations as well as helped to improve our understanding of the processes
      associated with degenerative disorders such as Parkinson's disease.

PMID- 15464129
TI  - Genetic and genomic approaches to reward and addiction.
AB  - Drug addiction is recognized as a mental disease affecting the brain's natural
      reward system. Drugs of abuse strongly activate reward structures in the brain
      and induce lasting changes in behavior that reflect changes in neuron physiology
      and biochemistry. With the ultimate goal of developing therapeutic interventions,
      it is of interest to determine the molecular and cellular components of
      motivation and reward, and identify those gene products that contribute to the
      process of drug addiction. Our laboratory has chosen three general genetic
      approaches to examine reward and addiction: reverse genetics to assess the role
      of candidate genes in drug responsiveness, forward genetics to discover novel
      regulators of dopamine transmission, and gene expression profiling to define gene
      sets in different brain structures that contribute to the molecular and
      neurobiological basis of reward.

PMID- 15464130
TI  - The search for the neurobiological basis of vulnerability to drug abuse: using
      microarrays to investigate the role of stress and individual differences.
AB  - Basic neurobiological studies have led to great progress in our understanding of
      the mechanisms of action of drugs of abuse. Much has been learned about the brain
      response from the moment a psychoactive drug enters the organism onwards,
      including the psychological, neurobiological and peripheral effects of repeated
      drug administration, withdrawal and re-exposure. However, to relate this
      knowledge to the human experience requires further research on the antecedents of
      drug-taking behavior and the factors that predispose particular individuals to
      drug seeking and drug abuse. Thus, it is important to address several issues at
      the fundamental level: (1) Why are some individuals more vulnerable to drugs of
      abuse more than others? Is there a broader dimension or dimensions of emotional
      reactivity that contribute to this difference in vulnerability? (2) What is the
      effect of psychosocial stress on drug-seeking and drug-taking behavior, and are
      the effects distinct across individuals? (3) Since both drug-taking behavior and
      stress have sustained and pervasive effects on the brain, can we use microarrays
      to discern the "neural signature" or "neural phenotype" associated with these
      processes, and can we distinguish this signature across individuals with
      differing propensities to taking drugs? In the present paper, we summarize some
      of our early attempts at addressing these questions. We rely on animal studies
      aimed at characterizing the emotional and stress reactivity of rats with
      different propensities to self-administer drugs (high responders and low
      responders); we briefly describe the effect of a psychosocial stressor on these
      animals; we then detail a study using microarray technology aimed at
      investigating the "neural phenotype" associated with social defeat stress in the
      high vs. low responder animals. This "discovery" approach is used as a starting
      place for identifying novel mechanisms that might alter the vulnerability of
      different individuals to drug-seeking behavior. The power and limits of this
      approach, and its future directions, are discussed within this general framework.

PMID- 15464131
TI  - Addiction research in a simple animal model: the nematode Caenorhabditis elegans.
AB  - Genetic analysis in the nematode C. elegans has provided important insights into
      many aspects of neuronal cell biology, including functions related to addiction.
      Specifically, genetic and molecular screens to have been used to identify
      molecules involved in long-term responses to drugs of abuse and to analyze the
      mechanisms underlying their effects on nervous system development, plasticity,
      and behavior. This review presents a personal view of addiction-related research
      in C. elegans, and includes a discussion of technical innovations that have
      facilitated neurobiological analyses in C. elegans and a look at future prospects
      drug addiction research in simple animal models.

PMID- 15464132
TI  - Beta2-subunit-containing nicotinic acetylcholine receptors are critical for
      dopamine-dependent locomotor activation following repeated nicotine
      administration.
AB  - Activation of the mesolimbic dopamine system is a critical component underlying
      addictive behaviors, including smoking. It has been hypothesized that the initial
      effect of nicotine on the dopamine system is to activate high affinity nicotinic
      acetylcholine receptors (nAChRs) containing the beta2 subunit, but that these
      receptors rapidly desensitize and are not critical for ongoing dopaminergic
      activation. To clarify the role of beta2-subunit-containing (beta2*) nAChRs in
      activation of the dopamine system and subsequent locomotor activation by repeated
      nicotine administration, C57BL/6J (B6) mice were administered 200 microg/ml of
      nicotine in the drinking water and the onset of locomotor activation was
      measured. B6 mice showed an increase in locomotor activity in response to chronic
      nicotine which was blocked by oral administration of the dopamine receptor
      antagonist pimozide. Knockout mice lacking the beta2 subunit of the nAChR did not
      show locomotor activation in response to chronic nicotine exposure, suggesting
      that beta2* nAChRs are critical for ongoing activation of the dopamine system by
      chronic nicotine administration and the resulting locomotor activation in mice.

PMID- 15464133
TI  - Molecular genetic underpinnings of human substance abuse vulnerability: likely
      contributions to understanding addiction as a mnemonic process.
AB  - Classical genetic studies document strong complex genetic contributions to abuse
      of multiple addictive substances. These genetic influences are more prominent in
      the later phases of individuals' progressions toward substance dependence.
      Individual differences in human addiction vulnerability could thus derive, in
      part, from individual differences in mnemonic systems. These variations could add
      to allelic variations that could produce effects on addiction vulnerability
      phenotypes by other routes that could include (1) differences in drug metabolism
      or biodistribution, (2) differences in drug's rewarding properties, (3)
      differences in traits manifest by the addict, including personality differences
      and (4) differences in the addict's psychiatric comorbidities. Data from linkage
      and association genome scans now identify chromosomal regions that are likely to
      contain allelic gene variants that contribute to human addiction vulnerability.
      Converging positive results are found in several different substance-abusing
      populations studied in several laboratories. This convergence supports the idea
      that common allelic variants contribute to individual differences in
      vulnerability to substance dependence. Genomic markers that identify allelic
      variants that reproducibly alter addiction vulnerability in several populations
      provide tools for research in addictions, tools to improve addiction treatments,
      tools to improve addiction prevention, clues to the genetic bases of individual
      differences in mnemonic processes and clues to the genetic bases of individual
      differences in the other traits and disorders that co-occur with substance
      dependencies.

PMID- 15464134
TI  - Recent advances in neuroproteomics and potential application to studies of drug
      addiction.
AB  - The rapidly growing field of proteomics seeks to track changes in protein
      expression function that underlie the growth and differentiation of individual
      cell types, both during normal development and during the onset and progression
      of disease. Recent years have seen great strides in mRNA expression analysis, and
      the development of new technologies for protein profiling. However, current
      methods are limited to analysis of the relative expression level of only a few
      hundred to perhaps 2000 proteins, well below the ability of DNA microarrays to
      potentially interrogate the mRNA expression of more than 25,000 genes. Proteomics
      faces a special challenge in studies of the nervous system, where cellular and
      sub-cellular architecture is among the most complex in the body. This article
      presents an overview of current proteomic profiling technologies, reviews the
      recent use of some of these approaches in studies of the nervous system, and
      discusses the potential application of neuroproteomics to studies of drug
      addiction.

PMID- 15464135
TI  - Brain substrates for increased drug seeking during protracted withdrawal.
AB  - Studies are reviewed indicating that both increased anxiety and altered hedonic
      processing accompany protracted withdrawal from opiates. Increased anxiety may be
      most apparent in response to stress, whereas decreased motivation for natural
      rewards but increased interest in drugs reveals substantial alterations in
      hedonic values. Our recent work indicates that increased norepinephrine (NE)
      release in the bed nucleus of the stria terminalis (BNST) may underlie anxiety
      associated with protracted withdrawal. Altered plasticity in afferents to the
      ventral tegmental area (VTA; accumbens, amygdala and lateral hypothalamus), or in
      the VTA itself, may be involved in the altered hedonic processing that occurs
      during protracted withdrawal. We hypothesize that conditioned release of NE in
      the BNST in response to stressors (including drug-associated stimuli) may elevate
      anxiety which then augments the reward value of drugs by a negative reinforcement
      mechanism. We also propose that plasticity in VTA neurons and their afferents
      during chronic drug exposure and protracted withdrawal decreases the valence of
      natural rewards whereas sensitization occurs to the motivational effects of drugs
      that increases their motivational valence. The combination of anxiety, decreased
      valence of natural rewards, and sensitized incentive for drugs make a potent
      formula for relapse and drug seeking during protracted withdrawal.

PMID- 15464136
TI  - Nucleus accumbens cell firing and rapid dopamine signaling during goal-directed
      behaviors in rats.
AB  - The nucleus accumbens (Acb) is a key neural substrate underlying goal-directed
      behaviors for both drugs of abuse as well as 'natural' rewards. Here, I review
      electrophysiological and electrochemical studies completed in our laboratory that
      examined Acb cell firing and rapid dopamine signaling during behaviors directed
      toward reward procurement. Electrophysiological studies are reviewed showing that
      Acb neurons exhibit patterned discharges relative to operant responding for
      intravenous self-administration of cocaine versus 'natural' reinforcement in
      rodents. Importantly, subsequent studies showed that discrete subsets of Acb
      neurons are selectively activated during multiple schedules for a natural reward
      (water or food) versus cocaine self-administration. These later findings indicate
      that separate neural circuits selectively process information about goal-directed
      behaviors for cocaine versus natural reward. In addition, recent findings are
      reviewed showing that reinforcer selective firing of Acb neurons is not a direct
      consequence of chronic drug exposure. Next, electrochemical studies are
      summarized that used fast scan cyclic voltammetry to measure rapid (subsecond)
      changes in dopamine in the Acb during cocaine self-administration as well as
      'natural' reinforcement in rodents. These findings are considered with respect to
      the role of dopamine in modulating the activity of Acb neurons that encode goal
      directed behaviors, the functional organization of the Acb on a microcircuit
      level, and proposed directions for future studies.

PMID- 15464137
TI  - Mapping of chemical trigger zones for reward.
AB  - Addictive drugs are thought to activate brain circuitry that normally mediates
      more natural rewards such as food or water. Drugs activate this circuitry at
      synaptic junctions within the brain; identifying the junctions at which this
      occurs provides clues to the neurochemical and anatomical characteristics of the
      circuitry. One approach to identifying the junctions at which drugs interact with
      this circuitry is to determine if animals will lever-press for site-specific
      microinjections of addictive drugs. This approach has identified GABAergic,
      dopaminergic, glutamatergic, and cholinergic trigger zones within meso
      corticolimbic circuitry important for natural reward function.

PMID- 15464138
TI  - Conditioned reinforcing properties of stimuli paired with self-administered
      cocaine, heroin or sucrose: implications for the persistence of addictive
      behaviour.
AB  - Conditioned environmental stimuli are known to be important determinants of drug
      seeking. Traditional models of drug seeking under the control of conditioned
      stimuli have focused on the ability of conditioned reinforcers either to
      reinstate extinguished responding or to maintain prolonged chains of drug seeking
      under second-order schedules. These models have consistently suggested that it is
      the conditioned reinforcing, rather than other, effects of Pavlovian drug stimuli
      that most profoundly influence drug seeking. However, the impact of drug
      associated conditioned reinforcers has not been studied directly and in
      isolation, not least because the instrumental seeking response is invariably the
      same as that which was previously reinforced with the drug itself. The purpose of
      the present study was, therefore, to investigate the conditioned reinforcing
      properties of drug-paired CSs using an acquisition of a new response procedure in
      which an animal learns to make a new instrumental response reinforced solely by
      the CS. It was found that CSs paired with either cocaine, heroin or sucrose
      supported the rapid acquisition of lever pressing for the CS that persisted over
      months of repeated, intermittent testing. Furthermore, rats did not acquire the
      lever press response when the CS was not paired with drug, suggesting that for
      this stimulus to acquire conditioned reinforcing properties, it must be
      predictively associated with the drug's effect. Moreover, lever pressing for the
      CS could not be explained as coincidental to an over-riding Pavlovian approach
      response to the location of the lever, since animals also acquired discriminated
      lever pressing when the CS was above the opposite, inactive lever. Extinction
      decreased responding with conditioned reinforcement, but only when the CS-US
      association was devalued prior to, and not after, acquisition of the lever press
      response, providing evidence for the establishment of habitual CS-maintained
      responding that may explain the persistence of drug-seeking responses in animal
      models of addiction and relapse.

PMID- 15464139
TI  - Incubation of cocaine craving after withdrawal: a review of preclinical data.
AB  - Using a rat model of drug craving and relapse, we recently found that cocaine
      seeking induced by re-exposure to drug-associated cues progressively increases
      over the first 2 months after withdrawal from cocaine self-administration,
      suggesting that drug craving incubates over time [Nature 412 (2001) 141]. Here,
      we summarize data from studies that further characterized this incubation
      phenomenon and briefly discuss its implications for drug addiction. The main
      findings of our ongoing research are: 1. Incubation of cocaine craving is long
      lasting, but not permanent: cocaine seeking induced by exposure to cocaine cues
      remains elevated for up to 3 months of withdrawal, but decreases after 6 months.
      2. Incubation of reward craving is not drug specific: sucrose seeking induced by
      re-exposure to the reward cues also increases after withdrawal, but for a time
      period that is shorter than that of cocaine. 3. Incubation of cocaine craving is
      not evident after acute re-exposure to cocaine itself: cocaine seeking induced by
      cocaine priming injections remains essentially unchanged over the first 6 months
      of withdrawal. 4. Incubation of cocaine craving after withdrawal is associated
      with increases in the levels of brain-derived neurotrophic factor (BDNF) in
      mesolimbic dopamine areas.

PMID- 15464140
TI  - Dopamine and drug addiction: the nucleus accumbens shell connection.
AB  - Microdialysis studies in animals have shown that addictive drugs preferentially
      increase extracellular dopamine (DA) in the n. accumbens (NAc). Brain imaging
      studies, while extending these finding to humans, have shown a correlation
      between psychostimulant-induced increase of extracellular DA in the striatum and
      self-reported measures of liking and 'high' (euphoria). Although a correlate of
      drug reward independent from associative learning and performance is difficult to
      obtain in animals, conditioned taste avoidance (CTA) might meet these
      requirements. Addictive drugs induce CTA to saccharin most likely as a result of
      anticipatory contrast of saccharin over drug reward. Consistently with a role of
      DA in drug reward, D2 or combined D1/D2 receptor blockade abolishes cocaine,
      amphetamine and nicotine CTA. Intracranial self-administration studies with
      mixtures of D1 and D2 receptor agonists point to the NAc shell as the critical
      site of DA reward. NAc shell DA acting on D1 receptors is also involved in
      Pavlovian learning through pre-trial and post-trial consolidation mechanisms and
      in the utilization of spatial short-term memory for goal-directed behavior.
      Stimulation of NAc shell DA transmission by addictive drugs is shared by a
      natural reward like food but lacks its adaptive properties (habituation and
      inhibition by predictive stimuli). These peculiarities of drug-induced
      stimulation of DA transmission in the NAc shell result in striking differences in
      the impact of drug-conditioned stimuli on DA transmission. It is speculated that
      drug addiction results from the impact exerted on behavior by the abnormal DA
      stimulant properties acquired by drug-conditioned stimuli as a result of their
      association with addictive drugs.

PMID- 15464141
TI  - Regulation of drug-taking and -seeking behaviors by neuroadaptations in the
      mesolimbic dopamine system.
AB  - Previous studies have identified several neuroadaptations to chronic drug use,
      but relatively few have been functionally linked to addiction-related changes in
      drug-taking and -seeking behaviors. This article summarizes our past and present
      studies on the contribution of drug-induced neuroadaptations in the mesolimbic
      dopamine system to addiction-related changes in drug self-administration and the
      propensity for relapse in drug withdrawal. Our studies suggest that drug-induced
      up-regulation in cyclic AMP (cAMP)-protein kinase A (PKA) signaling in the
      nucleus accumbens (NAc) contributes to escalating drug intake and a propensity
      for relapse by differentially altering the sensitivity of D1 and D2 dopamine
      receptors that regulate drug-taking and -seeking behaviors. In addition, our
      studies suggest that drug-induced neuroplasticity at excitatory synapses in both
      the ventral tegmental area (VTA) and the NAc also facilitates drug-seeking
      behavior and the propensity for relapse. Finally, the role of both transient and
      enduring neuroadaptations in regulating drug-seeking behavior is discussed in
      view of different learning- and memory-based interactions.

PMID- 15464142
TI  - Effects of dopamine indirect agonists and selective D1-like and D2-like agonists
      and antagonists on cocaine self-administration and food maintained responding in
      rats.
AB  - A procedure is described for comprehensive evaluation of the effects of acute
      drug pretreatments on the reinforcing effects of cocaine using the rat self
      administration assay in combination with a novel control assay of liquid-food
      maintained responding. In sessions comprised of five 20-min components, either
      complete dose-effect functions for cocaine self-administration or complete
      concentration-effect functions for liquid-food maintained responding were
      evaluated. The schedule of reinforcement (FR 5 TO 20-s), drug pretreatment doses
      and time intervals (0-30 min), and duration of sessions (108 min) were identical
      for cocaine- and food-reinforced test sessions. Whereas acute pretreatment with
      indirect dopamine agonists (D-amphetamine, GBR 12909) and D2-like agonists (7-OH
      DPAT, quinelorane) produced dose-dependent leftward shifts in dose-effect
      functions for cocaine self-administration, D1-like agonists (SKF 82958, R-6-Br
      APB) and dopamine antagonists (D1-like, SCH 39166; D2-like, eticlopride) shifted
      dose-effect functions for cocaine downward and rightward, respectively.
      Interestingly, with the indirect dopamine agonists but not the D2-like agonists,
      increased responding maintained by low cocaine doses was paralleled by increased
      responding maintained by low food concentrations. Moreover, three of the four
      direct agonists were moderately selective (< or =5-fold more potent) in
      decreasing cocaine self-administration relative to food maintained responding.
      When data were analyzed according to alterations in total cocaine intake, all of
      the agonists uniformly decreased total cocaine intake, whereas both antagonists
      increased total cocaine intake. Overall, this procedure was sensitive to
      leftward, downward and rightward shifts in cocaine dose-effect functions and
      should be useful for evaluating the nature of pharmacological interactions
      between novel compounds and self-administered cocaine, as well as the potential
      for altering cocaine self-administration selectively with candidate treatments
      for cocaine abuse and dependence.

PMID- 15464143
TI  - Opiate receptors and beyond: 30 years of neural signaling research.
AB  - Identification of opiate receptors some 30 years ago provided tools that brought
      major new insights into how these drugs act and led to the discovery of a novel
      group of atypical neurotransmitters, the peptide enkephalins being the first. The
      ligand binding techniques that were used to identify opiate receptors were
      employed to characterize receptors for all of the major neurotransmitters in the
      brain leading to additional insights into the actions of many drugs, such as
      neuroleptics. These techniques also permitted characterization of intracellular
      signaling systems such as the IP3 receptor and immunophilins. Even more novel
      than the enkephalins have been the gaseous neurotransmitters NO and CO and D
      serine.

PMID- 15464144
TI  - A cell biologist's perspective on physiological adaptation to opiate drugs.
AB  - Opiate drugs such as morphine and heroin are among the most effective analgesics
      known but are also highly addictive. The clinical utility of opiates is limited
      by adaptive changes in the nervous system occurring after prolonged or repeated
      drug administration. These adaptations are believed to play an important role in
      the development of physiological tolerance and dependence to opiates, and to
      contribute to additional changes underlying the complex neurobehavioral syndrome
      of drug addiction. All of these adaptive changes are initiated by the binding of
      opiate drugs to a subfamily of G protein-coupled receptors that are also
      activated by endogenously produced opioid neuropeptides. It is increasingly
      evident that opiate-induced adaptations occur at multiple levels in the nervous
      system, beginning with regulation of opioid receptors themselves and extending to
      a complex network of direct and indirect modifications of "downstream" signaling
      machinery. Efforts in my laboratory are directed at understanding the biochemical
      and cell biological basis of opiate adaptations. So far, we have focused
      primarily on adaptations occurring at the level of opioid receptors themselves.
      These studies have contributed to defining a set of membrane trafficking
      mechanisms by which the number and functional activity of opioid receptors are
      controlled. The role of these mechanisms in affecting adaptation of "downstream"
      neurobiological substrates, and in mediating opiate-induced changes in whole
      animal physiology and behavior, are exciting questions that are only beginning to
      be explored.

PMID- 15464145
TI  - Secrets of the opium poppy revealed.
AB  - Studies concerning drugs of abuse have made major contributions in defining the
      circuitry, as well as cellular and molecular substrates that underlie certain
      behaviors. Opiate drugs for example, have revealed important insights concerning
      pain perception and reward. Up to the late 1960s, opiate drugs were suspected to
      work by mysteriously perturbing lipid membrane structure. We now know the
      following: the sequence and neuroanatomy of the G-protein coupled receptors that
      mediate opiate effects; that many proteins interact with opioid receptors such as
      G-protein sub-unit combinations, G-protein receptor kinases, arrestins and
      calmodulin; that many signaling molecules are modulated by opioid receptors,
      including ion channels, kinase cascades and adenyl cyclase. More than 20
      different peptides, excised from three precursor proteins by specific proteases,
      have been shown to be endogenous ligands for opioid receptors. Revealing the
      molecules of the endogenous opioid system has inspired efforts for developing new
      opioid analgesics with the hope of minimizing abuse potential. This article will
      detail the current rationale for searching for less-addictive opiate analgesics
      and speculate on the future of drug abuse research in furthering our
      understanding of neural plasticity and the underpinnings of addictive behavior.

PMID- 15464146
TI  - Insights into the receptor transcription and signaling: implications in opioid
      tolerance and dependence.
AB  - Drug addiction has great social and economical implications. In order to resolve
      this problem, the molecular and cellular basis for drug addiction must be
      elucidated. For the past three decades, our research has focused on elucidating
      the molecular mechanisms behind morphine tolerance and dependence. Although there
      are many working hypotheses, it is our premise that cellular modulation of the
      receptor signaling, either via transcriptional or post-translational control of
      the receptor, is the basis for morphine tolerance and dependence. Thus, in the
      current review, we will summarize our recent work on the transcriptional and post
      translational control of the opioid receptor, with special emphasis on the mu
      opioid receptor, which is demonstrated to mediate the in vivo functions of
      morphine.

PMID- 15464147
TI  - Multiple opiate receptors: deja vu all over again.
AB  - The concept of multiple opioid receptors has changed dramatically since their
      initial proposal by Martin nearly 40 years ago. Three major opioid receptor
      families have now been proposed: mu, kappa and delta. Most of the opioid
      analgesics used clinically selectively bind to mu opioid receptors. Yet,
      clinicians have long appreciated subtle, but significant, differences in their
      pharmacology. These observations suggested more than one mu opioid receptor
      mechanism of action and led us to propose multiple mu opioid receptors over 20
      years ago based upon a range of pharmacological and receptor binding approaches.
      A mu opioid receptor, MOR-1, was cloned about a decade ago. More recent studies
      have now identified a number of splice variants of this clone. These splice
      variants may help explain the pharmacology of the mu opioids and open interesting
      directions for future opioid research.

PMID- 15464148
TI  - Evolving perspectives on neurobiological research on the addictions: celebration
      of the 30th anniversary of NIDA.
AB  - The roots of the Laboratory of the Biology of the Addictive Diseases are in the
      development of methadone maintenance for the treatment of opiate addiction.
      Methadone maintenance therapy continues to be one of the major effective forms of
      addiction pharmacotherapy and underscores the importance of biological factors in
      the physiology and treatment of the addictive diseases. Recent work in the
      Laboratory has focused on the neurobiological, neurochemical, neuroendocrine and
      behavioral aspects of addictive diseases (principally cocaine and the opiate
      addictions), using an interdisciplinary approach. The models we have focused on
      range from in vitro molecular biology and neuroscience, to in vivo animal models,
      to experiments in normal human populations and patients with specific addictive
      diseases, and most recently to the human molecular genetics of different
      addictive diseases. Two long-term corollary hypotheses have guided the
      Laboratory's work: (1) That the endogenous opioid peptide/receptor systems play a
      central role in the addictive states and therefore in their treatment. (2) That
      atypical responsivity to stressors (e.g., in the hypothalamic-pituitary-adrenal
      axis) plays a role in vulnerability and relapse to specific addictive diseases.
      This atypical responsivity may be drug-induced, environmentally acquired, and/or
      due to genetic variation.

PMID- 15464149
TI  - Cannabinoid physiology and pharmacology: 30 years of progress.
AB  - Delta9-Tetrahydrocannabinol from Cannabis sativa is mimicked by cannabimimetic
      analogs such as CP55940 and WIN55212-2, and antagonized by rimonabant and
      SR144528, through G-protein-coupled receptors, CB1 in the brain, and CB2 in the
      immune system. Eicosanoids anandamide and 2-arachidonoylglycerol are the
      "endocannabinoid" agonists for these receptors. CB1 receptors are abundant in
      basal ganglia, hippocampus and cerebellum, and their functional activity can be
      mapped during behaviors using cerebral metabolism as the neuroimaging tool. CB1
      receptors couple to G(i/o) to inhibit cAMP production, decrease Ca2+ conductance,
      increase K+ conductance, and increase mitogen-activated protein kinase activity.
      Functional activation of G-proteins can be imaged by [35S]GTPgammaS
      autoradiography. Post-synaptically generated endocannabinoids form the basis of a
      retrograde signaling mechanism referred to as depolarization-induced suppression
      of inhibition (DSI) or excitation (DSE). Under circumstances of sufficient
      intracellular Ca2+ (e.g., burst activity in seizures), synthesis of
      endocannabinoids releases a diffusible retrograde messenger to stimulate
      presynaptic CB1 receptors. This results in suppression of gamma-aminobutyric acid
      (GABA) release, thereby relieving the post-synaptic inhibition. Tolerance
      develops as neurons adjust both receptor number and cellular signal transduction
      to the chronic administration of cannabinoid drugs. Future therapeutic drug
      design can progress based upon our current understanding of the physiology and
      pharmacology of CB1, CB2 and related receptors. One very important role for CB1
      antagonists will be in the treatment of craving in the disease of substance
      abuse.

PMID- 15464150
TI  - The endogenous cannabinoid system and the treatment of marijuana dependence.
AB  - The active principle of marijuana, Delta9-tetrahydrocannabinol (Delta9-THC),
      exerts its pharmacological effects by binding to selective receptors present on
      the membranes of neurons and other cells. These cannabinoid receptors are
      normally engaged by a family of lipid mediators, called endocannabinoids, which
      are thought to participate in the regulation of a diversity of brain functions,
      including pain, mood, appetite and memory. Marijuana use may lead to adaptive
      changes in endocannabinoid signaling, and these changes might contribute to
      effects of marijuana as well as to the establishment of marijuana dependence. In
      the present article, I outline current views on how endocannabinoid substances
      are produced, released, and deactivated in the brain. In addition, I review
      recent progress on the development of pharmacological agents that interfere with
      endocannabinoid deactivation and discuss their potential utility in the treatment
      of marijuana dependence and other aspects of drug abuse.

PMID- 15464151
TI  - Modification of flavonoid biosynthesis in crop plants.
AB  - Flavonoids comprise the most common group of polyphenolic plant secondary
      metabolites. In plants, flavonoids play an important role in biological
      processes. Beside their function as pigments in flowers and fruits, to attract
      pollinators and seed dispersers, flavonoids are involved in UV-scavenging,
      fertility and disease resistance. Since they are present in a wide range of
      fruits and vegetables, flavonoids form an integral part of the human diet.
      Currently there is broad interest in the effects of dietary polyphenols on human
      health. In addition to the potent antioxidant activity of many of these compounds
      in vitro, an inverse correlation between the intake of certain polyphenols and
      the risk of cardiovascular disease, cancer and other age related diseases has
      been observed in epidemiological studies. The potential nutritional effects of
      these molecules make them an attractive target for genetic engineering strategies
      aimed at producing plants with increased nutritional value. This review describes
      the current knowledge of the molecular regulation of the flavonoid pathway and
      the state of the art with respect to metabolic engineering of this pathway in
      crop plants.

PMID- 15464152
TI  - Vitis vinifera terpenoid cyclases: functional identification of two sesquiterpene
      synthase cDNAs encoding (+)-valencene synthase and (-)-germacrene D synthase and
      expression of mono- and sesquiterpene synthases in grapevine flowers and berries.
AB  - Valencene is a volatile sesquiterpene emitted from flowers of grapevine, Vitis
      vinifera L. A full-length cDNA from the cultivar Gewurztraminer was functionally
      expressed in Escherichia coli and found to encode valencene synthase (VvVal). The
      two major products formed by recombinant VvVal enzyme activity with farnesyl
      diphosphate (FPP) as substrate are (+)-valencene and (-)-7-epi-alpha-selinene.
      Grapevine valencene synthase is closely related to a second sesquiterpene
      synthase from this species, (-)-germacrene D synthase (VvGerD). VvVal and VvGerD
      cDNA probes revealed strong signals in Northern hybridizations with RNA isolated
      from grapevine flower buds. Transcript levels were lower in open pre-anthesis
      flowers, flowers after anthesis, or at early onset of fruit development. Similar
      results were obtained using a third probe, (-)-alpha-terpineol synthase, a
      monoterpenol synthase. Sesquiterpene synthase and monoterpene synthase
      transcripts were not detected in the mesocarp and exocarp during early stages of
      fruit development, but transcripts hybridizing with VvVal appeared during late
      ripening of the berries. Sesquiterpene synthase transcripts were also detected in
      young seeds.

PMID- 15464153
TI  - Biosynthesis of 1-deoxynojirimycin in Commelina communis: a difference between
      the microorganisms and plants.
AB  - 1-Deoxynojirimycin is a glycosidase-inhibitory alkaloid obtained from several
      plants and microorganisms. Administration experiments using [1-(13C)] glucose in
      the higher plant Commelina communis and 13C NMR spectroscopic analyses of
      products suggested that 1-deoxynojirimycin was biosynthesized through a different
      route compared with that in Streptomyces and Bacilli microorganisms.

PMID- 15464154
TI  - The biosynthetic pathway to abscisic acid via ionylideneethane in the fungus
      Botrytis cinerea.
AB  - The biosynthetic pathway to abscisic acid (ABA) from isopentenyl diphosphate in
      the fungus, Botrytis cinerea, was investigated. Labeling experiments with (18)O2
      and H2(18)O indicated that all oxygen atoms at C-1, -1, -1' and -4' of ABA were
      derived from molecular oxygen, and not from water. This finding was inconsistent
      not only with the known carotenoid pathway via oxidative cleavage of carotenoids,
      but also with the classical direct pathway via cyclization of farnesyl
      diphosphate. The fungus produced new C15-compounds, 2E,4E-alpha-ionylideneethane
      and 2Z,4E-alpha-ionylideneethane, along with 2E,4E,6E-allofarnesene and 2Z,4E,6E
      allofarnesene, but did not apparently produce carotenoids except for a trace of
      phytoene. The C15-compounds labeled with 13C were converted to ABA by the fungus,
      and the incorporation ratio of 2Z,4E-alpha-ionylideneethane was higher than that
      of 2E,4E-alpha-ionylideneethane. From these results, it was concluded that
      farnesyl diphosphate was reduced at C-1, desaturated at C-4, and isomerized at C
      2 to form 2Z,4E,6E-allofarnesene before being cyclized to 2Z,4E-alpha
      ionylideneethane; the ionylideneethane was then oxidized to ABA with molecular
      oxygen. This direct pathway via ionylideneethane means that the biosynthetic
      pathway to fungal ABA, not only before but also after isopentenyl diphosphate,
      differs from that to ABA in plants, since plant ABA is biosynthesized using the
      non-mevalonate and carotenoid pathways.

PMID- 15464155
TI  - Labeling of major plant lipids and jasmonic acid using [1-(14C)] lauric acid.
AB  - A medium chain length fatty acid, [1-(14C)] lauric acid (12:0) was administered
      to the detached leaves of Artemisia and was incorporated into major lipids,
      including phospholipids and galactolipids. [1-(14C)]12:0 was elongated and
      desaturated into linolenic acid (18:3). In detached leaves of both Artemisia and
      Arabidopsis thaliana ecotype Columbia, radioactivity from [14C]18:3 was
      incorporated into jasmonic acid (JA) and methyl jasmonate (MJ). Higher amounts of
      [14C]JA were measured in Artemisia than Arabidopsis leaves. In Artemisia, [14C]JA
      was actively metabolized into [14C]MJ. Extracts prepared from the leaves of
      Artemisia, exhibited higher in vitro JA methyltransferase activity than those
      from Arabidopsis.

PMID- 15464157
TI  - Identification of unusual fatty acids of four alpine plant species from the
      Pamirs.
AB  - Fatty acid composition and structure in total lipids from the green above-ground
      parts of four alpine plants, Oxygraphis glacialis, Primula macrophylla, Rhodiola
      pamiroalaica, and Swertia marginata, were established by GC and GC-MS. A total of
      55 fatty acids was detected, and 48 of them were identified. Ubiquitous
      palmitate, linoleate, and linolenate predominated in the lipids accounting for
      about 72-90% of the total fatty acids. At the same time, the latter contained
      numerous species, which were unusual for higher plants and included saturated odd
      numbered n-acids (six C15-C25 species, 0.26-1.40%), saturated even-numbered very
      long-chain n-acids (six C20-C30 species, 1.00-2.49%), iso-acids (nine C15-C26
      species, 0.64-1.53%), anteiso-acids (four C15-C20 species, 0.08-1.57%), certain
      uncommon mono- and dienoic acids, as well as 16:3omega3, 18:3omega6, and
      18:4omega3 acids that are absent from the most higher plants. Nine fatty acids
      were found here for the first time in higher plants and two may be new to
      science. The evidence on the unusual fatty acids is discussed with respect to
      their distribution in living organisms, pathways of biosynthesis, and
      chemotaxonomic role.

PMID- 15464156
TI  - Detoxification of the cruciferous phytoalexin brassinin in Sclerotinia
      sclerotiorum requires an inducible glucosyltransferase.
AB  - The phytoalexins, brassinin, 1-methoxybrassinin and cyclobrassinin, were
      metabolized by the stem rot fungus Sclerotinia sclerotiorum into their
      corresponding glucosyl derivatives displaying no detectable antifungal activity.
      Importantly, co-incubation of S. sclerotiorum with camalexins, various
      phytoalexin analogs, and brassinin indicated that a synthetic camalexin
      derivative could slow down substantially the rate of brassinin detoxification.
      Furthermore, inducible brassinin glucosyltransferase (BGT) activity was detected
      in crude cell-free extracts of S. sclerotiorum. BGT activity was induced by the
      phytoalexin camalexin, and the brassinin analogs methyl tryptamine
      dithiocarbamate and methyl 1-methyltryptamine dithiocarbamate. The overall
      results suggest that the fungus S. sclerotiorum in its continuous adaptation and
      co-evolution with brassinin producing plants, has acquired efficient
      glucosyltransferase(s) that can disarm some of the most active plant chemical
      defenses.

PMID- 15464158
TI  - Isolation and characterization of limonoate and nomilinoate A-ring lactones.
AB  - A method combining solid-phase extraction and reversed-phase high-performance
      liquid chromatography is described for the isolation of two key metabolites in
      the limonoid biosynthetic pathway critical to citrus quality. Potassium salts of
      limonoate A-ring lactone and nomilinoate A-ring lactone were isolated from young
      Chandler pummelo seedlings and characterized on the basis of proton and carbon
      NMR data.

PMID- 15464159
TI  - NMRShiftDB -- compound identification and structure elucidation support through a
      free community-built web database.
AB  - Compound identification and support for computer-assisted structure elucidation
      via a free community-built web database for organic structures and their NMR data
      is described. The new database NMRShiftDB is available on . As the first NMR
      database, NMRShiftDB allows not only open access to the database but also open
      and peer reviewed submission of datasets, enabling the natural products community
      to build its first free repository of assigned 1H and 13C NMR spectra. In
      addition to the open access, the underlying database software is built solely
      from free software and is available under an open source license. This allows
      collaborating laboratories to fully replicate the database and to create a highly
      available network of NMRShiftDB mirrors. The database contains about 10,000
      structures and assigned spectra, with new datasets constantly added. Its
      functionality includes (sub-) spectra and (sub-) structure searches as well as
      shift prediction of 13C spectra based on the current database material.

PMID- 15464160
TI  - Antioxidant dehydrotocopherols as a new chemical character of Stemona species.
AB  - From the roots of various Stemona species four new dehydrotocopherols
      (chromenols) were isolated and their structures and stereochemistry elucidated by
      spectroscopic methods. The double bond between C-3 and C-4 proved to be a typical
      chemical character of the genus found in most of the species. Various C
      methylations of the aromatic ring reflect differences in methyltransferase
      activities and agreed with the current species delimitations showing an exclusive
      accumulation of dehydro-delta-tocopherol for the Stemona tuberosa group, whereas
      different provenances of Stemona curtisii were characterized by dehydro-gamma
      tocopherol accompanied by small amounts of dehydro-alpha-tocopherol. From Stemona
      collinsae all four tocopherols were isolated with a clear preponderance of
      dehydro-delta-tocopherol accompanied by smaller amounts of the rare dehydro-beta
      tocopherol. Stemona burkillii and a group of unidentified species showed a weak
      accumulation trend towards dehydro-alpha-tocopherol, whereas Stemona
      cochinchinensis and especially Stemona kerrii clearly differed by a preponderance
      of chromanol derivatives. In Stemona cf. pierrei no tocopherols could be detected
      at all. Based on TLC tests and microplate assays with the free radical 2,2
      diphenyl-1-picrylhydrazyl (DPPH*) the antioxidant capacities of all chromenol
      derivatives were comparable with that of alpha-tocopherol showing no significant
      differences among each other, except for a more rapid kinetic behaviour of the
      5,7,8-methylated dehydro-alpha-tocopherol.

PMID- 15464161
TI  - Ratification of tobacco treaty needed now.

PMID- 15464162
TI  - How would you like to be treated when you are 75?

PMID- 15464163
TI  - Vitamins to prevent cancer: supplementary problems.

PMID- 15464164
TI  - Pathomechanisms and molecular basis of membranous glomerulopathy.

PMID- 15464165
TI  - Testing for prions: a novel protocol for vCJD prevalence studies.

PMID- 15464166
TI  - Calcium supplementation for preventing colorectal cancer: where do we stand?

PMID- 15464167
TI  - Studies of nuclear workers: the pros and cons.

PMID- 15464168
TI  - Implications of the draft European Union services directive for health care.

PMID- 15464169
TI  - Obesity and culture.

PMID- 15464170
TI  - Evidence-based action needed on health systems.

PMID- 15464171
TI  - Historial keywords: resuscitation.

PMID- 15464172
TI  - AD2000: design and conclusions.

PMID- 15464173
TI  - Muller's ratchet hypothesis.

PMID- 15464174
TI  - AD2000: design and conclusions.

PMID- 15464175
TI  - AD2000: design and conclusions.

PMID- 15464176
TI  - AD2000: design and conclusions.

PMID- 15464179
TI  - Mercury in vaccines and potential conflicts of interest.

PMID- 15464180
TI  - Monkey malaria in man.

PMID- 15464181
TI  - Sir Arthur, Sir James, Sir Percivall, soot, and skin cancer.

PMID- 15464182
TI  - Antioxidant supplements for prevention of gastrointestinal cancers: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Oxidative stress can cause cancer. Our aim was to establish whether
      antioxidant supplements reduce the incidence of gastrointestinal cancer and
      mortality. METHODS: With the Cochrane Collaboration methodology, we reviewed all
      randomised trials comparing antioxidant supplements with placebo for prevention
      of gastrointestinal cancers. We searched electronic databases and reference lists
      (February, 2003). Outcome measures were incidence of gastrointestinal cancers,
      overall mortality, and adverse effects. Outcomes were analysed with fixed-effect
      and random-effects model meta-analyses and were reported as relative risk with
      95% CIs. FINDINGS: We identified 14 randomised trials (n=170,525). Trial quality
      was generally high. Heterogeneity of results was low to moderate. Neither the
      fixed-effect (relative risk 0.96, 95% CI 0.88-1.04) nor random-effects meta
      analyses (0.90, 0.77-1.05) showed significant effects of supplementation with
      beta-carotene, vitamins A, C, E, and selenium (alone or in combination) versus
      placebo on oesophageal, gastric, colorectal, pancreatic, and liver cancer
      incidences. In seven high-quality trials (n=131727), the fixed-effect model
      showed that antioxidant significantly increased mortality (1.06, 1.02-1.10),
      unlike the random-effects meta-analysis (1.06, 0.98-1.15). Low-quality trials
      showed no significant effect of antioxidant supplementation on mortality. The
      difference between the mortality estimates in high-quality and low-quality trials
      was significant (Z=2.10, p=0.04 by test of interaction). beta-carotene and
      vitamin A (1.29, 1.14-1.45) and beta-carotene and vitamin E (1.10, 1.01-1.20)
      significantly increased mortality, whereas beta-carotene alone only tended to
      increase mortality (1.05, 0.99-1.11). In four trials (three with unclear or
      inadequate methodology), selenium showed significant beneficial effect on the
      incidence of gastrointestinal cancer. INTERPRETATION: We could not find evidence
      that antioxidant supplements can prevent gastrointestinal cancers; on the
      contrary, they seem to increase overall mortality. The potential preventive
      effect of selenium should be studied in adequate randomised trials.

PMID- 15464183
TI  - Reduction of postoperative chemotherapy in children with stage I intermediate
      risk and anaplastic Wilms' tumour (SIOP 93-01 trial): a randomised controlled
      trial.
AB  - BACKGROUND: Present treatment for Wilms' tumour is very successful. Now, efforts
      are aimed at reducing toxicity and burden of treatment by shortening schedules
      without loss of effectiveness. The objective of this randomised trial was to
      assess whether postoperative chemotherapy for patients with stage I intermediate
      risk and anaplastic Wilms' tumour could be shortened to only 4 weeks from the
      standard 18 weeks, while maintaining equivalent event-free survival. METHODS:
      Between June, 1993, and June, 2000, 410 patients were randomly assigned after
      four doses of vincristine plus one course of dactinomycin postoperatively either
      to stop further adjuvant chemotherapy (no further chemotherapy group, n=200), or
      to receive a further two courses of the same chemotherapy (standard group,
      n=210). Previous treatment consisted of chemotherapy before nephrectomy of four
      doses of vincristine and two courses of dactinomycin followed by surgical
      resection of the tumour. Eligible patients were at least 6 months old and had
      stage I tumours with either intermediate-risk histology or anaplasia. The primary
      endpoint of this equivalence trial was 2-year event-free survival. Both per
      protocol and intention-to-treat analyses were done. FINDINGS: By 2 years, 18
      recurrences were reported in the standard group, and 22 in the no further
      chemotherapy group. Event-free survival was 91.4% (95% CI 87.5-95.2) for the no
      further chemotherapy group and 88.8% (84.3-93.2) for the standard group
      (difference=2.6%, upper 97.5% confidence limit 8.4%). The null hypothesis, that
      experimental treatment is less effective than standard treatment, could be
      rejected (p=0.008). CONCLUSIONS: Shortening duration of chemotherapy could reduce
      acute and late side-effects and inconvenience for patient and parents while
      maintaining effectiveness, and could be beneficial in terms of health costs.

PMID- 15464184
TI  - Mortality of infected and uninfected infants born to HIV-infected mothers in
      Africa: a pooled analysis.
AB  - BACKGROUND: HIV contributes substantially to child mortality, but factors
      underlying these deaths are inadequately described. With individual data from
      seven randomised mother-to-child transmission (MTCT) intervention trials, we
      estimate mortality in African children born to HIV-infected mothers and analyse
      selected risk factors. METHODS: Early HIV infection was defined as a positive HIV
      PCR test before 4 weeks of age; and late infection by a negative PCR test at or
      after 4 weeks of age, followed by a positive test. Mortality rate was expressed
      per 1000 child-years. We investigated the effect of maternal health, infant HIV
      infection, feeding practices, and age at acquisition of infection on mortality
      assessed with Cox proportional hazards models, and allowed for random effects for
      trials grouped geographically. FINDINGS: 378 (11%) of 3468 children died. By age
      1 year, an estimated 35.2% infected and 4.9% uninfected children will have died;
      by 2 years of age, 52.5% and 7.6% will have died, respectively. Mortality varied
      by geographical region, and was associated with maternal death (adjusted odds
      ratio 2.27, 95% CI 1.62-3.19), CD4+ cell counts <200 per microL (1.91, 1.39
      2.62), and infant HIV infection (8.16, 6.43-10.33). Mortality was not associated
      with either ever breastfeeding and never breastfeeding in either infected or
      uninfected children. In infected children, mortality was significantly lower for
      those with late infection than those with early infection (0.52, 0.39-0.70). This
      effect was also seen in analyses of survival from the age at infection (0.74,
      0.55-0.99). INTERPRETATION: These findings highlight the necessity for timely
      antiretroviral care, for support for HIV-infected women and children in
      developing countries, and for assessment of prophylactic programmes to prevent
      MTCT, including child mortality and infection averted.

PMID- 15464185
TI  - Two 8-month regimens of chemotherapy for treatment of newly diagnosed pulmonary
      tuberculosis: international multicentre randomised trial.
AB  - BACKGROUND: A WHO-recommended 8-month regimen based on ethambutol and isoniazid
      was evaluated in a randomised clinical trial against a 6-month standard regimen.
      METHODS: 1355 patients with newly diagnosed smear-positive pulmonary tuberculosis
      were randomly assigned one of three regimens: daily ethambutol, isoniazid,
      rifampicin, and pyrazinamide for 2 months, followed by ethambutol and isoniazid
      for 6 months (2EHRZ/6HE); the same drugs but given three times weekly in the
      initial intensive phase (2[EHRZ]3/6HE); or the same initial intensive phase as
      the first regimen, followed by 4 months of daily rifampicin and isoniazid
      (2EHRZ/4HR). Follow-up was to 30 months after the start of chemotherapy. Sputum
      was regularly examined by microscopy and culture. Unfavourable outcome was
      defined as failure during treatment or relapse afterwards. Analyses were by
      intention to treat. FINDINGS: At 2 months, a significantly higher proportion of
      patients assigned the daily intensive phase than of those assigned the three
      times-weekly regimen were culture negative (700/828 [85%] vs 333/433 [77%],
      p=0.001). 12 months after the end of chemotherapy, the proportions of
      unfavourable outcomes were 36 of 346 (10%) with 2EHRZ/6HE, 48 of 351 (14%) with
      2(EHRZ)3/6HE, and 17 of 347 (5%) with 2EHRZ/4HR. Both 8-month regimens were
      significantly inferior to the control 6-month standard regimen (difference
      between control and 2EHRZ/6HE 5.5% [95% CI 1.6 to 9.4]; between control and
      2(EHRZ)3/6HE 8.8% [4.5 to 13.0]). Adverse effects leading to interruption of
      treatment for 7 days or longer occurred in 28 patients (12 2EHRZ/6HE, five
      2[EHRZ]3/6HE, 11 2EHRZ/4HR). INTERPRETATION: The results of this study must be
      taken into account in recommendations on management of new cases of smear
      positive tuberculosis.

PMID- 15464186
TI  - Role of truncating mutations in MME gene in fetomaternal alloimmunisation and
      antenatal glomerulopathies.
AB  - BACKGROUND: Membranous glomerulonephritis is an immune-mediated disease. In a
      recent case of antenatal membranous glomerulonephritis, we identified neutral
      endopeptidase (NEP) as the podocyte target antigen of circulating antibodies
      produced by the mother who failed to express NEP on granulocytes. We aimed to
      investigate whether the disease could affect other families, to search for
      mutations in the metallomembrane endopeptidase (MME) gene for NEP, and to analyse
      the outcome of the antenatal renal insult. METHODS: From three families with a
      case of neonatal membranous glomerulopathy, we detected mutations by direct
      sequencing of genomic PCR products. Single nucleotide polymorphism (SNP) analysis
      was undertaken with five SNPs located in the MME gene. IgG subclasses with anti
      NEP activity were determined by western blotting. FINDINGS: In five mothers, we
      identified two compound heterozygous or homozygous mutations in the MME gene. The
      first, a 1342C-->T nonsense mutation, was detected in one family. The second,
      446delC, was detected in all three families; all chromosomes bearing this
      mutation had the same alleles for the five SNPs. Severity of neonatal renal
      disease was determined by the mothers' IgG response to fetal NEP antigens
      expressed on glomerular podocytes. The oldest affected individual, now aged 20
      years, has developed severe chronic renal failure. INTERPRETATION: Truncating
      mutations in the MME gene are the cause of alloimmunisation during pregnancy.
      Idiopathic renal failure in early adulthood might be caused by immune-mediated
      fetal nephron loss. We show that disease caused by fetomaternal alloimmunisation
      secondary to a genetic defect is not restricted to blood cells. RELEVANCE TO
      CLINICAL PRACTICE: During pregnancy, the absence of the NEP protein induces an
      alloimmunisation process against NEP presented by fetal cells, including
      syncytiotrophoblasts. The fetal podocyte insult and ensuing nephron loss could
      lead to chronic renal failure in early adulthood. Alloimmunisation against NEP
      should be considered as a leading cause of membranous glomerulopathy early in
      life. Concentrations of circulating anti-NEP antibodies should be carefully
      monitored during subsequent pregnancies, and specific therapeutic approaches
      developed. This new disease might also account for idiopathic chronic renal
      failure detected during adolescence, in individuals who can be identified by
      searching for anti-NEP antibodies in their mother and by MME gene mutation
      analysis. NEP deficiency should also be considered in patients developing de-novo
      membranous glomerulopathy after renal transplantation.

PMID- 15464187
TI  - Analysis of 2000 consecutive UK tonsillectomy specimens for disease-related prion
      protein.
AB  - Variant Creutzfeldt-Jakob disease (CJD) is thought to be caused by dietary or
      other exposure to bovine spongiform encephalopathy (BSE) prions. The prevalence
      of preclinical or subclinical prion infection in the UK is currently unknown.
      Since clinical variant CJD is uniformly associated with tonsillar prion
      infection, we screened 2000 anonymous surgical tonsillectomy specimens for
      disease-associated prion protein. Analysis by both high sensitivity
      immunoblotting and immunohistochemistry detected no positive cases. However, this
      negative result cannot provide reassurance that relevant community infection is
      unlikely because of the fairly small sample size, demographic and age-related
      factors, and unknown test sensitivity during the prolonged incubation period.
      Nevertheless, our findings establish a protocol for prevalence screening on a
      national scale.

PMID- 15464188
TI  - Elder abuse.
AB  - Elder abuse has received increasing attention over the past decade as a common
      problem with serious consequences for the health and wellbeing of old people. Our
      aim is to assist clinicians by summarising recent international research and
      clinical findings about elder abuse, and to assess their quality, relevance, and
      feasibility for health-care providers in clinical practice. This seminar includes
      issues of definition and frequency of elder abuse and a summary of major known
      risk factors. The advantages and disadvantages of screening for elder abuse are
      discussed. We review clinical manifestations and diagnosis of elder abuse, and
      propose a protocol for medical assessment of a patient with confirmed or
      suspected abuse. Suggestions for treatment are offered on the basis that elder
      abuse is multifactorial and needs individual medical and social intervention
      strategies, preferably in the context of a multidisciplinary team.

PMID- 15464189
TI  - Making health systems more equitable.
AB  - Health systems are consistently inequitable, providing more and higher quality
      services to the well-off, who need them less, than to the poor, who are unable to
      obtain them. In the absence of a concerted effort to ensure that health systems
      reach disadvantaged groups more effectively, such inequities are likely to
      continue. Yet this situation need not be accepted as inevitable, for there are
      many promising measures that might be pursued: establishment of goals for
      improved coverage in the poor, rather than in entire populations, and use of
      those goals to direct planning toward the needs of the disadvantaged; use of one
      or more of the several techniques that seem to have been effective in at least
      some of the settings where they have been tried; and empowerment of poor clients
      to have a more central role in health system design and operation.

PMID- 15464190
TI  - Take the side-effects of drugs into account.

PMID- 15464191
TI  - A drug user with a sore throat.

PMID- 15464192
TI  - Influence of nociceptin(1-17) fragments and its tyrosine-substituted derivative
      on morphine-withdrawal signs in rats.
AB  - Our previous studies demonstrated that endogenous ligand of nociceptin (NOP)
      receptor, nociceptin(1-17) (also known as orphanin FQ), inhibits morphine
      withdrawal syndrome measured as wet dog shakes in rats [Life Sci. 66 (2000)
      PL119]. This peptide is metabolized in the spinal cord, both in vitro and in
      vivo, to shorter fragments, including nociceptin(1-11) and nociceptin(1-6). These
      fragments, formed after cleavage by endogenous peptidase, are behaviorally active
      and modulate nociception in a bi-phasic process [Peptides 20 (1999) 239]. As
      these peptides induced transient naloxone-reversible analgesia in behavioral
      tests [Peptides 20 (1999) 239], in the present study we tested the influence of
      nociceptin(1-11) (10 and 20 microg) and nociceptin(1-6) (10, 20 and 40 microg) on
      the morphine-withdrawal syndrome in rats. Furthermore, the modified fragment of
      nociceptin(1-6) with an opioid-message domain achieved by replacement of Phe1
      with Tyr was tested. Morphine-withdrawal syndrome was precipitated by the i.p.
      injection of naloxone hydrochloride (2 mg/kg), 72 h after implantation of
      morphine pellets. The wet-dog shakes were chosen for statistical analyses of the
      abstinence signs. The results show that nociceptin(1-11) and (1-6) attenuate this
      morphine-withdrawal symptom. The replacement of Phe1 with Tyr in nociceptin(1-6)
      fragment did not potentiate the influence of nociceptin(1-6) on wet dog shakes
      precipitated by naloxone in morphine-dependent rats.

PMID- 15464193
TI  - Genotype-dependent effect of ACTH1-24 on grooming and yawning in two inbred
      strains of rats.
AB  - It has long been known that the intracerebroventricular administration of ACTH1
      24 increases the duration of grooming episodes and the frequency of yawning in
      rats. The objective of this study was to investigate in what way these episodes
      are prolonged and whether and to what extent genotype influences such effects. We
      compared the effect of increasing doses of intracerebroventricular injections of
      ACTH1-24 on grooming and yawning in males of two inbred strains of Sprague-Dawley
      rats with distinct yawning frequency, high-yawning (HY) and low-yawning (LY). In
      LY rats the duration of grooming episodes increased, while in HY rats grooming
      episodes augmented both in number and duration. In LY rats the duration of
      grooming components increased likewise, in HY rats however, neither the number
      nor the duration of the components changed. The grooming rate in both strains of
      rats was slowed, though more so in LY than in HY rats. Yawning increased in LY
      rats but not in HY rats. We conclude therefore that ACTH1-24 increases the
      duration of grooming episodes by slowing the grooming rate according to genotype,
      and may or may not alter the frequency of yawning.

PMID- 15464194
TI  - Coronary vascular effects of vasoactive intestinal peptide in the isolated
      perfused rat heart.
AB  - The potency and mechanism of action of vasoactive intestinal peptide (VIP) for
      producing coronary vasodilation was investigated in the isolated perfused heart
      of the rat. VIP reduced coronary vascular resistance in a dose-dependent manner,
      starting at 1 x 10(-10) M, and maximally reduced coronary vascular resistance by
      49% at 1 x 10(-8) M. The potency of VIP for reducing coronary vascular resistance
      (EC50=3.02 x 10(-10) M) was considerably greater than that of adenosine
      (EC50=6.17 x 10(-8) M) and sodium nitroprusside (EC50=2.45 x 10(-6) M). The
      vasodilatory action of VIP was more easily observed after increasing vascular
      tone by perfusion of the hearts with a modified physiological solution containing
      reduced concentrations of potassium (3.2 mM) and calcium (1.2 mM). Under these
      conditions, VIP maximally reduced coronary resistance by 54% at 7 x 10(-9) M. The
      potency of VIP for reducing coronary resistance in these hearts, however,
      decreased 16-fold (EC50=4.90 x 10(-9) M) while that of SNP remained unaltered
      (EC50=3.39 x 10(-6) M), compared with hearts perfused with higher levels of
      potassium (5.9 mM) and calcium (2.5 mM). The vasodilatory effect of VIP occurred
      without a significant change in heart rate, myocardial contractility or oxygen
      consumption. In additional studies, the dose-dependent effect of VIP on cyclic
      nucleotide release from the heart was determined by infusing VIP into the
      coronary circulation in a cumulative fashion to produce final concentrations
      between 1 x 10(-11) and 1 x 10(-9) M. VIP increased cyclic AMP at 1 x 10(-9) M
      but did not increase cyclic GMP. Studies using RT-PCR and immunohistochemistry
      clearly demonstrated the presence of two VIP receptor subtypes, VPAC1 and VPAC2,
      in the arteries and arterioles of the heart. In conclusion, VIP is a potent
      vasodilator in the coronary circulation of the rat and the role of VIP in the
      control of coronary vascular resistance depends on the circulating levels of
      potassium and calcium. This vasodilatory effect involves binding to specific
      coronary cell surface receptors, VPAC1 and/or VPAC2, and is dependent on cyclic
      AMP only during maximal vasodilation.

PMID- 15464195
TI  - Met-enkephalin modulates resistance to oxidative stress in mouse brain.
AB  - The purpose of this study was to investigate the effect of opioide peptide Met
      enkephalin (MENK) on resistance to oxidative stress in the brain of 4, 10 and 18
      months old CBA mice of both sexes. This was done by determination of oxidant
      status via lipid peroxidation (LPO) and antioxidant status by determination of
      total superoxide dismutase (tSOD), catalase (CAT) and glutathione peroxidase
      (Gpx). Results showed that brain of adult male mice is less resistant to
      oxidative stress than brain of adult females. The difference is mainly due to
      higher CAT activity and lower LPO activity in female brain. MENK decreased
      resistance to stress in the brain of both sexes but the effect appeared earlier
      in males (10 months of age) than in females (18 months of age). Also, MENK could
      pronounce its effect on resistance to oxidative stress in a gender-related
      manner: in female mice via regulation of antioxidant enzyme activities and in
      male mice via regulation of oxidant processes respectively.

PMID- 15464196
TI  - Endothelin ETB receptor signaling in the median eminence and subfornical organ of
      the rat brain.
AB  - We investigated the effect of endothelins (ETs) on receptor-mediated
      phosphoinositides (PI) turnover in whole subfornical organ (SFO) and median
      eminence (ME). Consistent with the presence of a high density of binding sites in
      the SFO and the ME of the rat brain, our results show an increase in PI
      hydrolysis induced by ETs in each structure, in a dose-dependent manner and with
      similar ED50 values. In addition, IRL 1620, a selective ETB receptor agonist,
      increased the inositol monophosphate (InsP1) accumulation in the SFO and the ME
      in a similar degree as ETs. With the use of selective agonists and antagonists of
      both endothelin receptor subtypes, we characterized the receptor subtype involved
      in ET-induced phosphoinositide metabolism. The addition of two selective ETA
      receptor antagonists, BQ 123 or BQ 610, did not alter the ETs-induced increase in
      the PI metabolism. While, IRL 1620- and ET3-induced InsP1 accumulation was
      completely blocked by BQ 788, a selective ETB receptor antagonist, in both brain
      structures evaluated. Our results demonstrate that in the SFO and the ME of the
      rat brain, stimulation of phosphoinositide turnover constitutes one of the
      signaling pathways of ETs, and this action is mediated through ETB receptor
      activation. These results support the concept that endothelin could play a role
      in the regulation of brain functions.

PMID- 15464197
TI  - Stereological analysis of the hypothalamic hypocretin/orexin neurons in an animal
      model of depression.
AB  - Affective disorders often occur in combination with disrupted sleep-wake cycles
      and abnormal fluctuations in hypothalamic neurotransmitters. Hypocretin (orexin)
      is a hypothalamic neuropeptide linked to narcolepsy, a sleep-related disorder
      characterized by profound disturbances in the normal sleeping pattern and
      variable degrees of depression. Wistar-Kyoto (WKY) rats exhibit depressive
      characteristics and patterns of sleep disruption similar to that observed in
      depressed human patients. In this study we sought to determine whether the total
      number or the size of hypothalamic hypocretin neurons in WKY rats differ from
      their control, Wistar (WIS) rats. Immunocytochemical and stereological methods
      were applied to quantify hypocretin-1 containing neurons in the hypothalamus. The
      study revealed 18% fewer hypocretin-1 positive neurons as well as a 15% decrease
      in average neuronal soma size of hypocretin-1 producing cells in the hypothalamus
      of WKY rats compared to WIS rats. These findings support the view that reduced
      number or size of hypothalamic hypocretinergic neurons may underlie the disrupted
      sleep pattern associated with depressive characteristics in WKY rats.

PMID- 15464198
TI  - Targeting of antisense PNA oligomers to human galanin receptor type 1 mRNA.
AB  - In this work, we have targeted positions 18-38 of the human galanin receptor type
      1 (GalR1) mRNA coding sequence with different peptide nucleic acid (PNA)
      oligomers. This region has previously been shown to be a good antisense region
      and therefore we aimed to identify the subregions and/or thermodynamic parameters
      determining the antisense efficacy. Nine different PNA oligomers were conjugated
      to a cell-penetrating peptide, transportan, to enhance their cellular uptake.
      Concentration-dependent down-regulation of GalR1 protein expression in human
      melanoma cell line Bowes was measured by radioligand binding assay. No reduction
      of GalR1 mRNA level was observed upon PNA treatment, thus, the effect was
      concluded to be translational arrest. Judging from the EC50 values, antisense PNA
      oligomers targeting regions 24-38 (EC50=70 nM) or 27-38 (EC50=80 nM) were the
      most potent suppressors of protein expression. No parameter predicted by M-fold
      algorithm was found to correlate with the measured antisense activities. Presence
      of some subregions was found not to increase antisense efficiency of PNA.
      Presence of a short unpaired triplet between nucleotides 33 and 35 in the target
      region was, on the other hand, found to be the most critical for efficient GalR1
      down-regulation. Thus, the results are of high impact in designing antisense
      oligomers. Specific results of this study demonstrate 20-fold more efficient
      antisense down-regulation of GalR1 as achieved before.

PMID- 15464199
TI  - Plasma levels of alpha-melanotropin and ACTH-like immunoreactivities do not vary
      by season or skin type in women from southern and central Europe.
AB  - Melanotropins (MSH) are involved in tanning by stimulating melanocytes via the
      activation of the melanocortin-1 receptor to melanin production. Its main site of
      production is the pituitary gland, but alpha-MSH and related ACTH peptides are
      produced at other sites, including the skin. It has been hypothesized that
      systemic levels of alpha-MSH are controlled by a varying UV radiation (UVR)
      exposure. A seasonal rhythm of plasma levels has been proposed by some authors.
      We investigated healthy females in southern Spain and central Austria in summer
      and winter. The alpha-MSH and ACTH-like immunoreactivity plasma levels did not
      present marked differences between the groups of Malaga and Linz, dark and light
      skin and between seasons. An association of alpha-MSH to ACTH or cortisol levels
      could not be observed. Individual values of alpha-MSH were shown to be relatively
      constant at both times of measurement (p<0.05 by rank correlation) indicating an
      independent personal disposition for individual systemic alpha-MSH
      immunoreactivity levels. Our data do not support the concept of a marked
      involvement of melanotropins of pituitary origin in tanning, and no seasonal
      rhythm was observed.

PMID- 15464200
TI  - Editorial.

PMID- 15464201
TI  - Evolution of nociception in vertebrates: comparative analysis of lower
      vertebrates.
AB  - Nociception is an important sensory system of major fundamental and clinical
      relevance. The nociceptive system of higher vertebrates is well studied with a
      wealth of information about nociceptor properties, involvement of the central
      nervous system and the in vivo responses to a noxious experience are already
      characterised. However, relatively little is known about nociception in lower
      vertebrates and this review brings together a variety of studies to understand
      how this information can inform the evolution of nociception in vertebrates. It
      has been demonstrated that teleost fish possess nociceptors innervated by the
      trigeminal nerve and that these are physiologically similar to those found in
      higher vertebrates. Opioid receptors and endogenous opioids are found in the
      brain and spinal cord of the fishes and morphine blocks avoidance learning using
      electric shock as well as reducing nociceptive behavioural and physiological
      responses to noxious stimulation. Comparative analysis of the fishes and higher
      vertebrates show that fish possess less C fibres than higher vertebrates. The
      electrophysiological properties of fish nociceptors are almost identical to those
      found in higher vertebrates suggesting the evolution of these properties occurred
      before the emergence of the fish groups.

PMID- 15464202
TI  - Abeta-fiber nociceptive primary afferent neurons: a review of incidence and
      properties in relation to other afferent A-fiber neurons in mammals.
AB  - The existence of nociceptors with Abeta-fibers has often been overlooked, and
      many textbooks endorse the view that all nociceptors have either C- or Adelta
      fibers. Here we review evidence starting from the earliest descriptions of A
      fiber nociceptors, which clearly indicates that a substantial proportion of
      cutaneous/somatic afferent A-fiber nociceptors conduct in the Abeta conduction
      velocity (CV) range in all species in which CV was carefully examined, including
      mouse, rat, guinea pig, cat and monkey. Reported proportions of A-fiber
      nociceptors with Abeta-fibers vary from 18% to 65% in different species, usually
      >50% in rodents. In rat, about 20% of all somatic afferent neurons with
      Aalpha/beta-fibers were nociceptive. Distributions of CVs of A-fiber nociceptors
      usually appear unimodal, with a median/peak in the upper Adelta or lower Abeta CV
      range. We find no evidence to suggest discontinuous differences in
      electrophysiological or cytochemical properties of Adelta and Abeta nociceptors,
      rather there are gradual changes in relation to CV. However, some functional
      differences have been reported. In cat, A-fiber nociceptors with lower mechanical
      thresholds (moderate pressure receptors) tend to have faster CVs [P.R. Burgess,
      D. Petit, R.M. Warren. Receptor types in cat hairy skin supplied by myelinated
      fibers. J. Neurophysiol. 31 (1968) 833-848]. In primate (monkey) A-fiber
      nociceptors that responded to heat were divided into type I A mechano-heat (AMH)
      units (Adelta and Abeta CVs) with lower mechanical and higher heat thresholds and
      may include moderate pressure receptors, and type II AMH units (Adelta CVs) with
      higher mechanical/lower heat thresholds. It is important that the existence of
      Abeta nociceptors is recognised, because assumptions that fast conducting, large
      diameter afferents are always low threshold mechanoreceptors might lead/have led
      to misinterpretations of data.

PMID- 15464203
TI  - Mechano-chemical nociceptors in the avian trigeminal mucosa.
AB  - This study characterised and compared the properties of chemically sensitive
      nociceptors in the avian nasal and oral epithelia recorded from either
      microelectrode stabs of the trigeminal ganglion (nasal mucosa) or microdissected
      twigs of the nasopalatine nerve (palatine mucosa) in urethane anaesthetized hens.
      A total of 146 slowly and rapidly adapting nasal and palate mechanically
      sensitive receptors were identified exhibiting von Frey thresholds to mechanical
      stimulation ranging from 0.2 to 8.3 g (mean 3.21+/-2.28 g, n=39) in the nasal
      cavity and <0.1 to 15 g (mean 2.17+/-2.69 g, n=62) in the palate. Receptive
      fields were situated throughout the nasal cavity and palate. A subset of
      receptors (classified as polymodal nociceptors) exhibited chemical sensitivity
      when exposed to noxious levels of ammonia gas, and some polymodal afferents also
      responded to acetic acid vapour or carbon dioxide exposure. Responses to ammonia
      were characterised by delayed onset, rapid prolonged discharge patterns usually
      outlasting the chemical stimulation. Clear concentration-response relationships
      were apparent for chemically receptive afferents in both the nasal and oral
      cavities, although curve shape varied considerably between receptors. Statistical
      comparisons of the responses of polymodal nociceptors in each mucosal region
      revealed no significant difference between their mechanical thresholds, but nasal
      afferents exhibited lower chemical (ammonia) thresholds and higher maximal firing
      rates. These response characteristics highlight distinct sensitivities to
      potentially painful chemical stimulation between epithelial areas. These effects
      may be due to the inherent properties of the nociceptors in each region but are
      also likely to reflect the role of the perireceptor environment in mediating
      peripheral nociception.

PMID- 15464204
TI  - Putative nociceptor responses to mechanical and chemical stimulation in skeletal
      muscles of the chicken leg.
AB  - Electrophysiological responses of nociceptive sensory afferent fibres in the
      skeletal muscle of the chicken (Gallus domesticus) were examined using mechanical
      and chemical stimulation. The activity of single nociceptive afferent fibres was
      recorded from micro-dissected filaments of the fibular and lateral tibial nerves,
      which innervate the fibularis longus and lateral gastrocnemius muscles. Seventeen
      putative nociceptive fibres were identified by mechanical stimulation (muscle
      compression). Conduction velocities (CVs) ranged from 2.8 to 11.3 m/s (mean 5.8;
      S.E.M.+/-0.9 m/s). Response thresholds to tissue compression ranged from 38 to
      126 kPa (mean 81; S.E.M.+/-4 kPa). Increases in pressure intensity, above
      individual fibre thresholds (x2 moderate; x3 noxious), produced intensity
      dependent increases in discharge rates. Fibres exhibited slowly adapting,
      irregular discharges lasting the duration of the stimulus and showed no
      spontaneous activity in the absence of mechanical stimulation. Intramuscular
      injection of acetic acid (1% v/v in isotonic saline; pH 2.8) in to the receptive
      field area stimulated discharge activity in 13 of the 17 (76%) pressure sensitive
      fibres. Acid injection resulted in prolonged irregular single or intermittent
      clustered discharges, which continued beyond the 15-min recording period. This
      study demonstrates the existence of nociceptive sensory fibres in chicken
      skeletal muscle that are able to respond to and encode acute tissue threatening
      and subjectively painful stimuli. The physiological characteristics of these
      nociceptive afferents are consistent with mammalian group III skeletal muscle
      nociceptors. These findings support the suggestion of a common, acute nociceptive
      response function in skeletal muscle in avians and other vertebrate classes.

PMID- 15464205
TI  - The organization of motor responses to noxious stimuli.
AB  - Withdrawal reflexes are the simplest centrally organized responses to painful
      stimuli, making them popular models for the study of nociception. Until recently,
      it was believed that withdrawal was a single reflex response involving excitation
      of all flexor muscles in a limb with concomitant inhibition of extensors.
      However, recent findings suggest that withdrawal reflexes are tailored to produce
      the most appropriate movement according the site at which the stimulus is
      applied, which could require extensors to act as the primary movers. This idea is
      supported by new evidence obtained from the direct measurement of limb movements,
      although these data indicate that differentiation of withdrawal reflexes is most
      readily seen from stimuli applied to the plantar surface of the foot. Injurious
      stimuli augment the protective function of reflexes by enhancing (sensitizing)
      reflexes that protect the injured site and inhibiting those reflexes that might
      exacerbate the insult. The areas from which a reflex can be sensitized closely
      match those from which the reflex itself can be evoked, provided that the spinal
      cord is intact. If descending pathways are interrupted, sensitization can be
      evoked from a much wider area. Thus, the exact movement made in a withdrawal
      reflex is determined by the location of the evoking stimulus and whether the
      reflex sensitized or inhibited after an injury depends on the relationship
      between the site of the injury and the movement made by the reflex. The factors
      should be borne in mind when designing experiments in which reflexes are used as
      the end point in studies of nociception.

PMID- 15464206
TI  - Spinal dorsal horn neurone targets for nociceptive primary afferents: do single
      neurone morphological characteristics suggest how nociceptive information is
      processed at the spinal level.
AB  - It has become increasingly clear that nociceptive information is signalled by
      several anatomically distinct populations of primary afferents that target
      different populations of neurones in the spinal cord. It is probable that these
      different systems all give rise to the sensation pain and hence, an understanding
      of their separate roles and the processes that they employ, may offer ways of
      selectively targeting pain arising from different causes. The review focuses on
      what is known of the anatomy of neurones in LI-III of the spinal dorsal horn that
      are implicated in nociception. The dendritic geometry and synaptic input of the
      large LI neurones that receive input from primary afferents containing substance
      P that express neurokinin 1 (NK(1)) receptors suggests that these neurones may
      monitor the extent of injury rather than the specific localisation of a discrete
      noxious stimulus. This population of neurones is also critically involved in
      hyperalgesia. In contrast neurones in LII with the morphology of stalked cells
      that receive primary afferent input from glomerular synapses may be more suitable
      for fine discrimination of the exact location of a noxious event such as a sting
      or parasite attack. The review focuses as far as possible on precisely defined
      anatomy in the belief that only by understanding these anatomical relationships
      will we eventually be able to interpret the complex processes occurring in the
      dorsal horn. The review attempts to be an accessible guide to a sometimes complex
      and highly specialised literature in this field.

PMID- 15464207
TI  - A model of organotypic rat spinal slice culture and biolistic transfection to
      elucidate factors that drive the preprotachykinin-A promoter.
AB  - The tachykinin substance P (SP) is a neuropeptide that is expressed in some
      nociceptive primary sensory afferents and in discrete populations of spinal cord
      neurons. Expression of spinal SP and the preprotachykinin-A (PPT-A) gene that
      encodes SP exhibits plasticity in response to conditions such as peripheral
      inflammation but the mechanisms that regulate expression are poorly understood.
      We have developed a spinal cord organotypic culture system that is suitable for
      the analysis of PPT-A gene promoter activity following biolistic transfection of
      recombinant DNA constructs. Spinal cord organotypic slices showed good viability
      over a 7-day culture period. Immunostaining for phenotypic markers such as NeuN
      and beta-III tubulin demonstrated preservation of neurons and their structure,
      although there was evidence of axotomy-induced down-regulation of NeuN in certain
      neuronal populations. Neurokinin-1 receptor (NK-1R) immunostaining in laminae I
      and III was similar to that seen in acute slices. Biolistic transfection was used
      to introduce DNA constructs into neurons of these organotypic cultures. Following
      transfection with a construct in which expression of enhanced green fluorescent
      protein (EGFP) is controlled by the PPT-A promoter, we showed that induction of
      neuronal activity by administration of a forskolin analogue/high K(+) (10
      microM/10 mM) for 24 h resulted in a fourfold increase in the number of EGFP
      positive cells. Similarly, a twofold increase was obtained after treatment with
      the NK-1R-specific agonist [Sar(9),Met (O(2))(11)]-substance P (10 microM). These
      data demonstrate the usefulness of this model to study physiological and
      pharmacological factors relevant to nociceptive processing that can modulate PPT
      A promoter activity.

PMID- 15464209
TI  - Nociception in vertebrates: key receptors participating in spinal mechanisms of
      chronic pain in animals.
AB  - Our view of vertebrate nociceptive processing is ever changing with the discovery
      of novel molecules that differentially affect sensory responses to noxious and
      innocuous stimulation and might be involved specifically in chronic pain states.
      In order to understand the physiology of nociception and design novel analgesics
      for intractable chronic pain, it is essential to uncover precisely what changes
      occur between a normal nociceptive processing state and hypersensitive chronic
      pain states in the spinal cord following different types of injury. An important
      area of focus for future work in this area will be the cellular and molecular
      mechanisms of neuronal plasticity that occur.

PMID- 15464208
TI  - Opioid research in amphibians: an alternative pain model yielding insights on the
      evolution of opioid receptors.
AB  - This review summarizes the work from our laboratory investigating mechanisms of
      opioid analgesia using the Northern grass frog, Rana pipiens. Over the last dozen
      years, we have accumulated data on the characterization of behavioral effects
      after opioid administration on radioligand binding by using opioid agonist and
      antagonist ligands in amphibian brain and spinal cord homogenates, and by cloning
      and sequencing opioid-like receptor cDNA from amphibian central nervous system
      (CNS) tissues. The relative analgesic potency of mu, delta, and kappa opioids is
      highly correlated between frogs and other mammals, including humans. Radioligand
      binding studies using selective opioid agonists show a similar selectivity
      profile in amphibians and mammals. In contrast, opioid antagonists that are
      highly selective for mammalian mu, delta, and kappa opioid receptors were not
      selective in behavioral and binding studies in amphibians. Three opioid-like
      receptor cDNAs were cloned and sequenced from amphibian brain tissues and are
      orthologs to mammalian mu, delta, and kappa opioid receptors. Bioinformatics
      analysis of the three types of opioid receptor cDNAs from all vertebrate species
      with full datasets gave a pattern of the molecular evolution of opioid receptors
      marked by the divergence of mu, delta, and kappa opioid receptor sequences during
      vertebrate evolution. This divergence in receptor amino acid sequence in later
      evolved vertebrates underlies the hypothesis that opioid receptors are more type
      selective in mammals than in nonmammalian vertebrates. The apparent order of
      receptor type evolution is kappa, then delta, and, most recently, the mu opioid
      receptor. Finally, novel bioinformatics analyses suggest that conserved
      extracellular receptor domains determine the type selectivity of vertebrate
      opioid receptors.

PMID- 15464210
TI  - Discovering genes: the use of microarrays and laser capture microdissection in
      pain research.
AB  - The DNA microarray is a powerful, high throughput technique for assessing gene
      expression on a system-wide genomic scale. It has great potential in pain
      research for determining the network of gene regulation in different pain
      conditions, and also for producing detailed gene expression maps in anatomical
      areas that process nociceptive stimuli. However, for the potential of this high
      throughput technology to be realised in pain research, microarrays need to be
      combined with other technologies. Laser capture microdissection is capable of
      isolating small populations of homogenous cells, allowing distinct areas involved
      in nociceptive processing to be examined. In combination with sophisticated PCR
      based amplification protocols this technique provides sufficient amounts of
      messenger RNA (mRNA) for application to microarrays. Aside from the technological
      issues, a difficult task in any microarray study is the analysis of the resulting
      enormous data set to reveal the key genes, whose regulation is central to the
      phenotypic changes observed. For this to be achieved, the methods of data
      analysis, pattern searching and feature recognition, and bioinformatics have to
      be properly deployed all within the context of an appropriate statistical design.
      These issues are especially relevant to pain research where interindividual and
      interpopulation variation is likely to be high, and where polymorphisms can
      greatly affect nociceptive sensitivity and susceptibility to pain conditions.
      Methods for assessing the function of new candidate genes identified in
      microarray screening experiments are also discussed.

PMID- 15464211
TI  - Allodynia in rats infected with varicella zoster virus--a small animal model for
      post-herpetic neuralgia.
AB  - The most common complication of herpes zoster is post-herpetic neuralgia (PHN),
      which has been defined as severe pain occurring 1 month after rash onset or
      persisting for greater than 3 months. PHN is classed as a neuropathic pain that
      is associated with mechanical allodynia where normally innocuous tactile stimuli
      are perceived as painful. The development of therapies to treat PHN has been
      hampered by the lack of animal models, which mimic the clinical situation. We
      have previously reported that varicella zoster virus (VZV) infection in the rat
      results in mechanical allodynia and thermal hyperalgesia. Here, we report that
      following VZV infection of the left footpad rats develop a chronic mechanical
      allodynia, which is present for longer than 60 days post-infection and which
      resolves by 100 days PI. The model is robust and reproducible with animals
      consistently developing allodynia by 3 days PI and continuing to present with
      symptoms for at least 30 days. The reproducible nature of the induction and
      course of the allodynia allows the use of this model to determine the effect of
      various compounds on, and to investigate the pathogenic mechanisms underlying the
      development of VZV-induced allodynia. Comparative studies using HSV-1 show that
      the induction of the chronic allodynia is VZV-specific and is not a result is of
      virus replication-induced tissue damage or accompanying inflammation. Therefore,
      we propose that the rat VZV infection model could prove useful in studying the
      mechanisms underlying post-herpetic neuralgia.

PMID- 15464212
TI  - Loss of glial glutamate transporters and induction of neuronal expression of GLT
      1B in the hypoxic neonatal pig brain.
AB  - The homeostasis of glutamate is critical to normal brain function; deficiencies
      in the regulation of extracellular glutamate are thought to be a major
      determinant of damage in hypoxic brains. Extracellular levels of glutamate are
      regulated mainly by plasmalemmal glutamate transporters. We have evaluated the
      distribution of the glutamate transporter GLAST and two splice variants of GLT-1
      in the hypoxic neonatal pig brain using this as model of neonatal humans. In
      response to severe hypoxic insults, we observe a rapid loss of two glial
      glutamate transporters from specific brain regions, such as the CA1 region of the
      hippocampus, but not the dentate gyrus. The spatial distribution of loss accords
      with patterns of damage in these brains. Conversely, we demonstrate that hypoxia
      evokes the expression of a splice variant of GLT-1 in neurons. We suggest that
      this expression may be induced in response to elevated extracellular glutamate
      around these neurons, and that this splice variant may represent a useful marker
      for direct quantification of the extent of likely neuronal damage in hypoxic
      brains.

PMID- 15464213
TI  - Role of allopregnanolone on cerebellar granule cells neurogenesis.
AB  - The role of allopregnanolone on immature cerebellar granule cells (CGC)
      proliferation was studied. Allopregnanolone (0.1-1 microM) increased
      [(3)H]thymidine incorporation and cell number determined by neuronal counting and
      by an MTT colorimetric assay. The effect of the neurosteroid was completely
      prevented by preincubation with 10 mM MgCl(2), 10 microM nifedipine, 10 microM
      picrotoxin or by 50 microM bicuculine. We conclude that ALLO affects cerebellar
      neurogenesis by increasing calcium influx through voltage-gated calcium channels
      and GABA(A) receptors activation.

PMID- 15464214
TI  - Mouse neural progenitor cells differentiate into oligodendrocytes in the brain of
      a knockout mouse model of Canavan disease.
AB  - Canavan disease (CD) is an autosomal recessive disorder that leads to spongy
      degeneration in the white matter of the brain. Aspartoacylase (ASPA) synthesizing
      cells, oligodendrocytes, are lost in CD. Transplantation of neural progenitor
      cells (NPCs) offers an interesting therapeutic approach for treating
      neurodegenerative diseases by replacing the lost cells. Therefore, the NPCs
      transplantation to the brain of the CD mouse was studied. Injection of mouse NPCs
      to the striatum and cerebellum of juvenile CD mouse showed numerous BrdU positive
      cells at 1 month after injection. The same result was also observed in the adult
      CD mouse brain after 5 weeks of post-transplantation period. The implanted cells
      differentiated into oligodendrocytes and fibrous astrocytes, as observed using
      glial cell marker. This is the first report to describe the survival,
      distribution and differentiation of NPCs within the brain of CD mouse and a first
      step toward the potential clinical use of cell therapy to treat CD.

PMID- 15464215
TI  - Distribution and postnatal development of alpha 7 nicotinic acetylcholine
      receptors in the rodent lower auditory brainstem.
AB  - The distribution and quantity of the alpha 7 nicotinic acetylcholine receptor
      (nAChR) were mapped in the nuclei of the superior olivary complex, lateral
      lemniscus, and inferior colliculus in the developing and mature rat brain.
      Radioactive in situ hybridization and (125)I-alpha-bungarotoxin receptor binding
      were used to measure alpha 7 transcript and membrane-bound protein, respectively.
      The highest transcript and protein levels were found in the external nucleus of
      the inferior colliculus and paraolivary nucleus. More moderate levels of
      transcript and protein were measured in the ventral, intermediate, and dorsal
      nuclei of the lateral lemniscus, lateral and medial ventral posterior olivary
      nuclei, rostral periolivary region, lateral periolivary nucleus, caudal
      periolivary region, ventral and dorsal trapezoid nuclei, medial superior olive,
      and the lateral superior olive. Peak receptor expression generally occurred
      before the onset of hearing. The significant overlap of transcript and protein in
      these regions suggests that the alpha 7 nAChR is predominantly localized
      postynaptically on somata or proximal dendrites. In a separate experiment, alpha
      7 transcript was quantified in the superior olivary complex, lateral lemniscus,
      and inferior colliculus of +/+ and null mutant (-/-) mice for the
      acetylcholinesterase (AChE) gene. The distribution and quantity of alpha 7 nAChR
      were not different in +/+ and -/- mice, suggesting that AChE may not induce or
      regulate alpha 7 transcription during the early postnatal period.

PMID- 15464216
TI  - The differentiation potential of human foetal neuronal progenitor cells in vitro.
AB  - Previously, this laboratory has shown that human foetal progenitor cells derived
      from ventral mesencephalon (VM) can be developmentally directed towards a
      dopaminergic lineage. In the present study, the effects are reported of several
      as yet untested differentiation/survival factors on the controlled conversion of
      neural progenitor cells to dopaminergic neurons. Positive immunoreactivity to
      tyrosine hydroxylase (TH) and raised levels of dopamine (DA) and its metabolite,
      3,4-dihydroxyphenylacetic acid (DOPAC), secreted into culture medium, were used
      to indicate the presence of the dopaminergic neuronal phenotype, i.e., active TH.
      Incubation with retinoic acid (RA) (0.5 microM) lead to an increase in the number
      of cultured cells showing positive immunoreactivity for the neuronal marker,
      microtubule-associated protein (MAP)-2ab. A concomitant increase in TH-positive
      immunoreactivity was also demonstrated. The brain-derived neurotrophic factor
      (BDNF) (50 ng/ml), glial-derived neurotrophic factor (GDNF) (10 ng/ml) and
      interleukin-1 beta (IL-1 beta) (10 ng/ml) also had positive effects in promoting
      neural progenitor cell differentiation towards the dopaminergic phenotype in the
      presence of dopamine (10 microM) and forskolin (Fsk) (10 microM). There was no
      synergy in this effect when progenitor cells were incubated with all of these
      agents simultaneously. The trans-differentiation potential of the progenitor
      cells to be directed towards other neurotransmitter phenotypic lineages was also
      investigated. It was found that, with the right cocktails of agents, serotonin
      (Ser) (75 microM), acidic fibroblast growth factor (aFGF) (10 ng/ml), BDNF (50
      ng/ml) and forskolin (10 microM), these same cells could be directed down the
      serotonergic cell lineage pathway (as judged by the appearance of tryptophan
      hydroxylase (TPH) positive immunoreactivity, and synthesis of 5-HT and its
      metabolites, secreted into the culture medium). However, no cocktail containing
      noradrenaline (10 nM-500 microM), BDNF (50 ng/ml) and forskolin (10 microM) was
      found which promoted differentiation towards the noradrenergic cell phenotype as
      judged by the absence of any TH or D beta H positive immunoreactivity, and no
      formation of 3,4-dihydroxyphenylethyleneglycol (DOPEG), the principal metabolite
      of noradrenaline. The controlled trans-differentiation potential of these cell
      could pave the way for development and harvesting of large numbers of neurons of
      the appropriate neurotransmitter phenotype for future transplantation therapies
      for the treatment of neurodegenerative diseases such as Parkinson's disease (PD)
      and Alzheimer's disease.

PMID- 15464217
TI  - Induced fetal depressor or pressor responses associated with c-fos by intravenous
      or intracerebroventricular losartan.
AB  - Previous fetal studies have indicated depressor responses of intravenous (i.v.)
      administration of angiotensin antagonists. However, little is known of central
      effects of angiotensin blockers on fetal cardiovascular controlling. The
      cardiovascular effects of central administration of the angiotensin-1 (AT(1)) and
      angiotensin-2 (AT(2)) receptor antagonists, losartan and PD123319, were
      investigated in the chronically catheterized near-term ovine fetuses. Intravenous
      losartan produced within 1.5 min a significant and persistent depressor response
      [maximum Delta mean arterial pressure (MAP)=9 mm Hg] without altering fetal heart
      rate. Intracerebroventricular (i.c.v.) administration of losartan (1-5 mg/kg)
      increased fetal arterial pressures (Delta MAP=9-14 mm Hg). Central application of
      losartan (1 mg/kg) also increased fetal heart rate (maximum Delta heart rate=33
      beat per minute). Losartan increased c-fos expression in the median preoptic
      nucleus and paraventricular nuclei in the forebrain, and the tractus solitarius
      nuclei, the lateral parabrachial nuclei, and the ventrolateral medullabrain.
      These brain sectors are with abundant AT(1) receptors and have been demonstrated
      in the involvement in cardiovascular regulation. In contrast,
      intracerebroventricular injection of the AT(2) receptor antagonist PD123319 had
      no effect on fetal arterial pressure and heart rate. The results demonstrate
      strikingly functional differences of losartan on the fetal cardiovascular
      regulation in central and peripheral sides.

PMID- 15464218
TI  - Maternal vitamin D3 deprivation and the regulation of apoptosis and cell cycle
      during rat brain development.
AB  - Recently, it has been shown that the prenatal vitamin D(3) depletion is
      associated with altered brain development. Given the antiproliferative and pro
      apoptotic properties of vitamin D(3) in various cell types, we examined the
      effects of maternal vitamin D(3) deprivation on cell proliferation and apoptosis
      within the rat cortex at several developmental stages. Our results confirm that
      vitamin D(3) regulates these processes in the developing brain at both cellular
      and molecular levels. Compared to control animals, the embryos and pups from
      vitamin D(3) depleted mothers had significantly less apoptotic cells, this
      finding being most pronounced at birth. Additionally, there were significantly
      more mitotic cells but this was not associated with any particular developmental
      period. Targeted gene arrays specific for apoptosis and cell cycle genes
      confirmed a pattern of transcription deregulation in the deplete group consistent
      with the known properties of vitamin D(3). While most current vitamin D(3)
      research is focussed on the pro-apoptotic and prodifferentiating properties of
      vitamin D(3) as adjuncts for the treatment of cancers, our findings highlight the
      important role that this hormone plays in normal development via these same
      properties specifically in the brain.

PMID- 15464219
TI  - Behavioural consequences of hypergravity in developing rats.
AB  - Gravity represents a stable reference for the nervous system. When the individual
      is increasing in size and weight, gravity may influence several aspects of the
      sensory and motor developments. To clarify this role, we studied age-dependent
      modifications of several exteroceptive and proprioceptive reflexes in five groups
      of rats conceived, born and reared in hypergravity (2 g). Rats were transferred
      to normal gravity (1 g) at P5 (post-natal day 5), P10, P15, P21, and P27. Aspects
      of neural development and adaptation to 1 g were assessed until P40. Hypergravity
      induced a delay in growth and a retardation in the development of contact
      righting, air-righting, and negative geotaxis. However, we found an advance in
      eye opening by about 2-3 days in HG-P5 and HG-P10 rats and an increase in grip
      time. No differences were found in tail and grasp reflexes. Our results show that
      hypergravity leads to a retarded development of motor aspects which are mainly
      dependent upon the vestibular system.

PMID- 15464220
TI  - Recovery, innervation profile, and contractile properties of reinnervating fast
      muscles following postnatal nerve crush and administration of L-Dopa.
AB  - Muscle and peripheral nerve development is clearly dependent on their interaction
      during early postnatal life. Furthermore, muscle or peripheral nerve activity
      plays a crucial role in the maturation of the neuromuscular system. In this
      study, the possible involvement of spinal catecholamines in fast muscle recovery
      after nerve crush is investigated. Sciatic nerve crush was performed on the
      fourth to fifth postnatal day. Following that, L-Dopa was administered daily [150
      mg/kg body weight (BW)] i.p., until the 21st day after birth. L-Dopa-treated and
      control groups were then examined electrophysiologically for the contractile
      properties of extensor digitorum longus (EDL) muscles. Two experimental groups
      were included in this study: (i) rats whose sciatic nerve was crushed and were
      treated with L-Dopa and (ii) rats whose sciatic nerve was crushed and were not
      treated with L-Dopa. The number of motoneurones for both groups was estimated by
      HRP retrograde labelling. The results showed that the operated L-Dopa-treated EDL
      muscles of the rats exhibited limited atrophy, slighter impairment of maximal
      tetanic tension, lesser resistance to fatigue, and polyneuronal innervation than
      the controls. The number of motoneurones was the same for the operated muscles in
      both groups of animals and was within the normal ranges. Our findings suggest
      that catecholamines of locomotion during the early stages of development may have
      a beneficial effect on fast muscle recovery following nerve crush. The action of
      L-Dopa is attributed to noradrenaline, which acts through descending spinal
      noradrenergic pathways, possibly via a(2)-adrenergic receptors at the spinal
      level.

PMID- 15464221
TI  - Properties of cortical precursor cells cultured long term are similar to those of
      precursors at later developmental stages.
AB  - In vitro cultures of neural precursor cells are useful experimental tools for
      studies on the mechanisms of brain development, as well as for generating
      renewable sources in cell therapy for neurodegenerative disorders. The systematic
      characterization of cultured neural precursors is a prerequisite for obtaining
      basic information on brain development. Here, we examine the cell survival,
      proliferation, and differentiation potential of cultured neural precursors from
      different embryonic ages and those of the precursors expanded in vitro for
      different periods of time. Precursor cells were isolated at rat embryonic days 14
      (E14) and 19 (E19) and cultured in the presence of a mitogen basic fibroblast
      growth factor (bFGF). The numbers of TUNEL+ and BrdU+ cells in E19 cortical
      precursor cultures were significantly lower than those in E14 cultures,
      indicating that the programmed cell death and proliferation potential of neural
      precursors are reduced during the progression of brain development. E14 cells
      tended to differentiate into neurons, and E19 cells into astrocytes. To determine
      whether the intrinsic properties of neural precursors are similarly altered
      during in vitro culture, E14 precursor cells were expanded for different periods.
      Precursor cells expanded for longer periods displayed lower apoptotic and
      proliferation indices, as well as astrogenic developmental potential. Clonal
      analysis data confirmed the transition of precursor differentiation potential
      from neurogenic to astrogenic over the culture period. Our findings collectively
      suggest that neural precursor cells undergo time-dependent changes in properties
      via an intrinsic program, both in vivo and in vitro.

PMID- 15464222
TI  - Developmental changes of transient potassium currents in large aspiny neurons in
      the neostriatum.
AB  - Developmental regulation of the potassium conductance is important for the
      maturation of neuronal excitability and the formation of functional circuitry in
      the central nervous system (CNS). The rapidly inactivating A-type current is a
      major component of the voltage-dependent outward potassium currents in the large
      aspiny (LA) neurons in the neostriatum. The large aspiny neurons play important
      roles in the function of neostriatum in physiological and pathological
      conditions. Whole-cell patch-clamp recording was performed on acutely dissociated
      neurons and brain slices to investigate the postnatal development of A-type
      current in the large aspiny neurons. The current density of A-type current in
      large aspiny neurons was the highest at postnatal 1-3 days and gradually
      decreased during the development with the lowest levels in adult animals. In
      comparison to postnatal 1-3 days, the steady-state inactivation curve shifted in
      depolarizing direction in mature neurons. No significant changes in the voltage
      dependence of steady-state activation were observed during development.
      Consistent with the decrease in the current density of A-type current during
      development, the latency to the first spike was dramatically shortened in mature
      large aspiny neurons. These results suggest that the decrease of rapidly
      inactivating A-type potassium current during development might contribute, at
      least in part, to the maturation of the membrane excitability of large aspiny
      neurons in the neostriatum.

PMID- 15464223
TI  - Hypothyroidism alters the development of radial glial cells in the term fetal and
      postnatal neocortex of the rat.
AB  - Alterations of thyroid function during human development are known to produce
      extensive damage to the central nervous system including severe mental
      retardation. Using immunohistochemistry to identify the intermediate filament
      nestin, we have studied the possible influence of fetal and neonatal
      hypothyroidism on neocortical neuronal migration by arresting the normal
      development of the radial glial scaffold. By embryonic day 21 (E21), hypothyroid
      animals had a significant decrease in the number of nestin immunoreactive
      processes in the presumptive visual cortex. By postnatal day 5 (P5), hypothyroid
      animals showed a significant increase in the number of glial processes in
      relation with controls, although only in the upper layers of the visual cortex.
      Moreover, by P10, there was a marked increase in the number of radial glial
      processes in hypothyroid animals in superficial and deep zones of the visual
      cortex with respect to control animals. Our data indicate an important delay in
      the formation of the radial glial scaffold during the embryonic stage in
      hypothyroid animals that was interestingly accompanied by the later presence of
      abundant nestin immunoreactive fibers at P10. This impairment in the evolution of
      radial glia during development might be affecting the normal neuronal migratory
      pattern in the neocortex of hypothyroid rats.

PMID- 15464224
TI  - Expression of the winged helix/forkhead gene, foxn4, during zebrafish
      development.
AB  - The winged-helix/forkhead transcription factor gene, foxn4, is expressed in the
      nervous system of developing and adult zebrafish. Prominent expression sites
      include the olfactory placode, the basal layer of the olfactory epithelium, the
      neuroepithelium of the developing retina, the germinal zone of the differentiated
      eye, regions of motoneuron development in the neural tube and periventricular
      regions of the brain. The adult thymus is the only major site of foxn4 expression
      outside of the nervous system.

PMID- 15464225
TI  - Developmental expression of glial fibrillary acidic protein mRNA in mouse
      forebrain germinal zones--implications for stem cell biology.
AB  - Postnatal neural stem cells (NSCs) express the "traditional" astrocyte marker,
      glial fibrillary acidic protein (GFAP). Here, we analyze the ontogeny of GFAP
      mRNA in mouse forebrain germinal zones (GZ). On embryonic day 15, mRNA
      distribution is highly restricted. Subsequently, expression expands to include
      many cells in the GZ regions adjacent to the cortex and septum but not to the
      striatum. Double immunostaining for GFAP and nestin did not demonstrate extensive
      overlap in the GZ of adult rats, suggesting that either few of the GFAP
      expressing cells are stem cells, or that nestin is not a reliable marker for stem
      cells in the adult rat brain. The current findings indicate that while some GFAP
      expressing cells in the GZ may be NSCs, most are not likely to function in a
      neurogenic capacity.

PMID- 15464226
TI  - Preweaning cocaine exposure alters brain glucose metabolic rates following
      repeated amphetamine administration in the adult rat.
AB  - Developmental cocaine exposure produces long-term alterations in function of many
      neuronal circuits. This study examined glucose metabolic rates following repeated
      amphetamine administration in adult male and female rats pretreated with cocaine
      during postnatal days (PND) 11-20. PND11-20 cocaine increased the response to
      amphetamine in many components of the motor system and the dorsal caudate
      putamen, in particular, and decreased the metabolic response in the hypothalamus.
      While amphetamine alone produced widespread increases in metabolism, there were
      no cocaine-related effects in the mesolimbic, limbic or sensory structures. These
      data suggest that a brief cocaine exposure during development can alter ontogeny
      and result in abnormal neuronal responses to repeated psychostimulant
      administration in adulthood.

PMID- 15464227
TI  - Expression of Btcl2, a novel member of Btcl gene family, during development of
      the central nervous system.
AB  - Cell-cell interactions are primarily mediated by secreted and transmembrane
      proteins which play essential roles in the neuronal circuit formation. However,
      molecular mechanisms underlying neuronal circuit formation, which is mediated by
      the cell-cell interactions, remain largely elusive. We isolated and characterized
      a novel gene, Btcl2 (brain-specific transmembrane protein containing CUB
      [complement subcomponent C1r/C1s, sea urchin protein Uegf, and BMP-1] and LDLa
      [low-density lipoprotein receptor domain class A] domains 2), using the signal
      sequence trap (SST) method. The extracellular domain of BTCL2 contains two CUB
      domains and an LDLa domain. BTCL2 and BTCL1 have similar domain structures,
      sharing 51% overall identity. The CUB1, CUB2, and LDLa domains of these two
      proteins share 63%, 72%, and 84% identity, respectively. The CUB domains of BTCL1
      and BTCL2 share significant identity with those of neuropilins. Btcl2 mRNA was
      detected as a single 6-kb transcript in Northern blot analysis. In situ
      hybridization (ISH) analysis revealed that both Btcl1 and Btcl2 mRNAs were
      observed restrictively in brain throughout embryonic and postnatal stages. Btcl1
      and Btcl2 mRNAs were expressed uniquely in the pontine nucleus and subplate,
      which are required for establishing the neuronal circuit formation. These results
      will aid in resolving the mechanisms underlying neuronal circuit formations
      (e.g., pontocerebellar and thalamocortical axon guidance) and permit more precise
      studies aimed at understanding the role of BTCL1 and BTCL2 in the central nervous
      system.

PMID- 15464228
TI  - Identification of chick and mouse Daam1 and Daam2 genes and their expression
      patterns in the central nervous system.
AB  - Genes controlling the planar cell polarity (PCP) pathway have recently been
      described in Drosophila. Although a number of PCP-related genes were identified,
      it remains unknown whether the same genetic programs found in invertebrate
      embryos operate in vertebrate embryos, especially with regard to central nervous
      system development. To gain insights into the roles played by vertebrate PCP
      related genes, we cloned and examined the expression patterns of chick and mouse
      homologues of the Xenopus Daam gene, an essential component of the PCP pathway
      and involved in the convergent extension movement of cells. The observed
      expression patterns in developing central nervous tissues suggested that
      vertebrate Daam genes were involved in pivotal steps in neuronal cell
      differentiation and movement.

PMID- 15464230
TI  - Virologically compromised donor grafts in liver transplantation.

PMID- 15464231
TI  - Spontaneous bacterial peritonitis: a historical perspective.

PMID- 15464232
TI  - cAMP stimulates the secretory and proliferative capacity of the rat intrahepatic
      biliary epithelium through changes in the PKA/Src/MEK/ERK1/2 pathway.
AB  - BACKGROUND/AIMS: To evaluate if increased cholangiocyte cAMP levels alone are
      sufficient to enhance cholangiocyte proliferation and secretion. METHODS: Normal
      rats were treated in vivo with forskolin for two weeks. Cholangiocyte apoptosis,
      proliferation and secretion were evaluated. Purified cholangiocytes from normal
      rats were treated in vitro with forskolin in the absence or presence of Rp-cAMPs
      (a PKA inhibitor), PP2 (an Src inhibitor) or PD98059 (a MEK inhibitor).
      Subsequently, we evaluated cholangiocyte proliferation by determination of
      proliferating cellular nuclear antigen (PCNA) protein expression by immunoblots.
      We evaluated if the effects of forskolin on cholangiocyte functions are
      associated with changes in the cAMP/PKA/Src/MEK/ERK1/2 pathway. RESULTS: Chronic
      administration of forskolin to normal rats increased the number of ducts, cAMP
      levels, and secretin-induced choleresis compared to controls. Forskolin-induced
      increases in cholangiocyte proliferation and secretion were devoid of
      cholangiocyte necrosis, inflammation and apoptosis. In vitro, in pure isolated
      cholangiocytes, forskolin increased cholangiocyte proliferation, which was
      ablated by Rp-cAMPs, PP2 and PD98059. The effects of forskolin on cholangiocyte
      proliferation were associated with increased activity of PKA, Src Tyrosine 139
      (Tyr 139) and ERK1/2. CONCLUSIONS: Modulation of the PKA/Src/MEK/ERK1/2 pathway
      may be important in the regulation of cholangiocyte growth and secretion observed
      in cholestatic liver diseases.

PMID- 15464233
TI  - Up-regulation of the high-affinity pyrimidine-preferring nucleoside transporter
      concentrative nucleoside transporter 1 by tumor necrosis factor-alpha and
      interleukin-6 in liver parenchymal cells.
AB  - BACKGROUND/AIMS: Concentrative nucleoside transporter 1 (CNT1), a high affinity
      transporter for pyrimidine nucleosides, is responsible for their Na+-dependent
      concentrative uptake into hepatocytes. Though CNT1 protein amounts increase in
      rat liver soon after partial hepatectomy, the physiological regulators of CNT1
      expression have not yet been identified. METHODS: Rat hepatoma cell lines and
      hepatocytes isolated from fetuses and adult rats were used to identify single
      agents able to up-regulate CNT1 expression and activity in liver. TNF-alpha
      receptor-I (TNFRI) and IL-6 knock-out mice were also used to study CNT1
      regulation in vivo. RESULTS: TNF-alpha and IL-6 independently induced CNT1
      protein expression in cultured liver parenchymal and FAO hepatoma cells by PI-3
      kinase- and ERK-dependent mechanisms, respectively. In vivo data showed that
      transporter protein levels were low in livers from TNFRI knock-out mice, but not
      in those from IL-6 deficient animals. However, IL-6 administration only partially
      restored CNT1 expression in the former model. CONCLUSIONS: This study identifies
      TNF-alpha as a major in vivo modulator of the nucleoside transporter CNT1 and
      suggests a secondary role for IL-6 in mediating CNT1 up-regulation by TNF-alpha
      in vivo. Evidence is provided that two independent pathways are involved in the
      up-regulation of CNT1 by TNF-alpha and IL-6.

PMID- 15464234
TI  - Basic fibroblast growth factor promotes the trans-differentiation of mouse bone
      marrow cells into hepatic lineage cells via multiple liver-enriched transcription
      factors.
AB  - BACKGROUND/AIMS: Evidence that bone marrow cells have trans-differentiating
      potential to hepatocytes has been described in recent reports. However, the
      molecular mechanism underlying this phenomenon is unclear. To address this issue,
      we investigated the parameters involved in the trans-differentiation of bone
      marrow cells into a hepatic lineage. METHODS: Mouse BM cells were cultured in a
      collagen gel without or with growth factors including basic fibroblast growth
      factor. The expression of hepatocyte-specific markers, cholangiocyte-specific
      marker and liver-enriched transcription factors was identified by RT-PCR and
      immunohistochemistry. RESULTS: Basic fibroblast growth factor was found to be the
      most effective for inducing albumin in cultured BM cells. Furthermore, on
      stimulation of basic fibroblast growth factor, BM cells were found to express
      other hepatocyte-specific markers and a cholangiocyte-specific marker. This
      conversion was found to be associated with the induction of transcription factors
      including hepatocyte nuclear factors and GATA family proteins. CONCLUSIONS: We
      established an in vitro culture system in which mouse bone marrow cells could
      trans-differentiate to hepatic lineage cells in response to growth factors,
      without cell fusion. In particular, basic fibroblast growth factor has the
      ability to induce the trans-differentiation into hepatic lineage cells from BM
      cells.

PMID- 15464235
TI  - Bleeding ectopic varices--treatment with transjugular intrahepatic porto-systemic
      shunt (TIPS) and embolisation.
AB  - BACKGROUND/AIMS: Bleeding ectopic varices due to cirrhosis can be difficult to
      manage. We report our experience of uncontrolled bleeding from ectopic varices
      treated with transjugular intrahepatic porto-systemic shunt (TIPS). METHODS: We
      selected the 21 cirrhotics who underwent TIPS for bleeding ectopic varices from
      our database: Child-Pugh grade A (2), B (11) and C (8). Site of bleeding was
      rectal (11), colonic (2), ileal 1, jejunal 1, duodenal 1, and stomal (5).
      RESULTS: TIPS was performed successfully in 19/21 (90%) patients. All except 1
      had either a reduction in portosystemic pressure gradient < or = 12 mmHg (n=12)
      or reduction by 25-50% of baseline (n=6). TIPS alone was used in 12/19: 7 of
      these 12 had no further bleeding; 5 (42%) rebled within 48 h, and had
      embolisation, 4 without further bleeding. In 7 of 19, TIPS and embolisation were
      performed together: 2 patients (28%) rebled; further embolisation stopped the
      bleeding. CONCLUSIONS: Ectopic varices do rebleed despite a reduction of porto
      systemic pressure gradient < or = 12 mmHg or by 25-50% of baseline, following
      TIPS. Embolisation stopped bleeding in all but 1 patient. We recommend performing
      embolisation at the time of the initial TIPS to control bleeding from ectopic
      varices.

PMID- 15464236
TI  - Superoxide-induced apoptosis of activated rat hepatic stellate cells.
AB  - BACKGROUND/AIMS: During liver injury, reactive oxygen species (ROS) are produced
      by the resident macrophages (Kupffer cells) and infiltrating blood cells such as
      neutrophils. ROS cause transformation of desmin-positive quiescent hepatic
      stellate cells (HSCs) into the proliferating activated phenotype that expresses
      alpha-smooth muscle actin (alpha-SMA). The highly fibrogenic and contractile
      activated HSCs (aHSCs) produce various cytokines and growth factors, and play
      important role in the pathophysiology of chronic liver disease. However,
      apoptotic aHSCs are also observed during active fibrogenesis in the injured
      liver. Therefore, we investigated the mechanisms of apoptosis of aHSCs in
      relation to ROS. METHODS: HSCs, isolated from normal rat liver, were activated in
      culture and effects of superoxide were determined between subcultures 3 and 5.
      RESULTS: Treatment with superoxide caused apoptosis of aHSCs as determined by
      flow cytometry, TUNEL assay and DNA laddering analysis. The mechanisms of
      superoxide-induced apoptosis involved release of cytochrome c, increased Bax
      expression, increased caspase-3 activity, and hydrolysis of polyADP-ribose
      polymerase. Superoxide also increased the expression of antiapoptotic Bcl-xL and
      nuclear translocation of NFkappaB. Caspase-3 inhibitor (DEVD-fmk) and
      antioxidants (N-acetylcysteine, vitamin E and superoxide dismutase) inhibited
      superoxide-induced apoptosis. CONCLUSIONS: Superoxide-induced apoptosis of aHSCs
      may be a novel mechanism of limiting chronic fibrotic liver injury.

PMID- 15464237
TI  - Serum markers of hepatic fibrogenesis in cystic fibrosis liver disease.
AB  - BACKGROUND/AIMS: Hepatic fibrosis contributes to adverse outcome in cystic
      fibrosis (CF). Early detection of CF liver disease (CFLD) may identify patients
      at risk of significant complications. To evaluate the utility of serum markers to
      detect hepatic fibrosis in children with CFLD vs. CF patients without liver
      disease (CFnoLD) and controls. METHODS: Sera from 36 CFLD, 30 CFnoLD and 39
      controls were assessed for tissue inhibitor of matrix metalloproteinase (MMP)
      (TIMP)-1, collagen (CL)-IV, MMP-2, hyaluronic acid (HA) and prolyl hydroxylase
      (PH) by enzyme immunoassay and were correlated with hepatic fibrosis score in
      CFLD. RESULTS: TIMP-1, PH and CL-IV were increased in CFLD vs. CFnoLD and
      controls. Fibrosis score was negatively correlated with TIMP-1 (r=-0.34, P=0.06)
      and PH (r=-0.48, P=0.008). Receiver-operating characteristics analysis showed CL
      IV (AUC 0.785, P<0.0001) and TIMP-1 (AUC 0.765, P<0.0001) differentiated CFLD
      from CFnoLD and controls, while PH (AUC 0.814, P<0.0001) predicted early
      fibrogenesis. Diagnostic accuracy improved using logistic regression combining
      (i) CL-IV, TIMP-1, PH to identify CFLD (AUC 0.831, P<0.0001) and (ii) TIMP-1, PH
      to identify CFLD patients with no fibrosis (AUC 0.852, P<0.02). CONCLUSIONS:
      Elevated TIMP-1, CL-IV, PH may be indicators of hepatic fibrogenesis in CF.
      Increased TIMP-1, PH may be early markers of CFLD.

PMID- 15464238
TI  - Japanese herbal medicine Inchin-ko-to as a therapeutic drug for liver fibrosis.
AB  - BACKGROUND/AIMS: Inchin-ko-to (TJ-135) is an herbal medicine used in Japan for
      treatment of icteric patients with cirrhosis. Its efficacy as an anti-fibrogenic
      drug was evaluated in relation to stellate cell activation. METHODS/RESULTS:
      Liver fibrosis was induced in rats by repeated injections of carbon tetrachloride
      (CCl4) or pig-serum. Oral administration of TJ-135 improved the mortality of rats
      given CCl4 with reduced extents of liver necrosis and fibrosis. Similar
      improvement of liver fibrosis was found in rats given pig-serum showing no liver
      necrosis. DNA synthesis of stellate cells activated in vitro after isolation from
      normal rat liver was decreased by culture with TJ-135 in a dose-related manner,
      accompanied by decreased smooth muscle alpha actin expression and contractility.
      Such attenuation was not found in the cells cultured with geniposide, an iridoid
      compound of TJ-135, but genipin, an aglycone of geniposide formed in the gut by
      action of bacterial flora, markedly decreased stellate cell activation without
      affecting synthesis of proteins other than collagen. CONCLUSIONS: TJ-135 may be
      useful for treatment of liver fibrosis and portal hypertension through
      suppression of activated hepatic stellate cell function by genipin, an absorbed
      form of its component.

PMID- 15464239
TI  - Pentoxifylline attenuates steatohepatitis induced by the methionine choline
      deficient diet.
AB  - BACKGROUND/AIMS: Feeding mice a methionine choline deficient (MCD) diet serves as
      a nutritional model of non-alcoholic steatohepatitis (NASH). NASH and alcohol
      induced steatohepatitis are histologically similar, suggesting a similar
      pathogenesis. Pentoxifylline (PTX) attenuates TNF-alpha production, acts as an
      antioxidant and decreases mortality in alcoholic steatohepatitis. The aim of our
      study is to determine if PTX attenuates MCD diet induced steatohepatitis and
      determine the mechanism of this effect. METHODS: Mice were placed on an MCD or
      control diet for 2 weeks and were treated with or without PTX. Serum ALT, liver
      histology, and inflammatory mechanisms were evaluated. RESULTS: PTX attenuates
      MCD diet induced steatohepatitis, decreasing both serum ALT levels and hepatic
      inflammation. Serum ALT levels were reduced approximately 50% in the MCD+PTX
      group compared to the MCD group. Hepatic glutathione levels were significantly
      higher in the MCD+PTX group compared to the MCD group. There was also a reduction
      in TNF-alpha mRNA in female mice treated with PTX. MCD+PTX mice had increased
      hepatic triglyceride content compared to the MCD mice, but less histologic
      evidence of inflammation despite the increased steatosis. Serum lipid and bile
      salt levels also were similar in PTX and vehicle control treated mice.
      CONCLUSIONS: PTX decreases serum ALT levels and hepatic inflammation in the MCD
      model of steatohepatitis, likely via increasing glutathione levels or reducing
      TNF-alpha expression.

PMID- 15464240
TI  - Improvement of C3A cell metabolism for usage in bioartificial liver support
      systems.
AB  - BACKGROUND/AIMS: The use of cell lines in bioartificial liver support systems
      (BALSS) to treat fulminant hepatic failure (FHF) is hindered by their reduced
      metabolic functions, which could be further decreased by the patient's
      serum/plasma. Hence, the aim of this study was to (i) test the effect of the FHF
      serum on C3A cell metabolism; (ii) precondition the cells to improve their
      metabolic capacity. METHODS: C3A cells were preconditioned in a medium developed
      at the University of Edinburgh (UoE) or a 10% FHF serum medium. Metabolism
      capacity was assessed on days 3, 7 and 10 and compared with primary porcine
      hepatocytes. Preconditioned-cell metabolism was reassessed after (i) passage and
      (ii) incubation with 10% FHF serum. RESULTS: UoE-preconditioned cells showed time
      dependent increase in gluconeogenesis (500%), ureogenesis (200%), galactose
      elimination (240%) albumin synthesis (250%). These results were in the same order
      of magnitude as the ones obtained with primary porcine hepatocytes and were
      further enhanced by cell passage. UoE-preconditioning prevented the decrease of
      metabolism induced by acute incubation with FHF serum on control C3A cells.
      Preconditioning with FHF serum did not improve cell metabolism. CONCLUSIONS: Cell
      preconditioning with UoE-medium increases metabolic capacity and would greatly
      improve BALSS efficacy.

PMID- 15464241
TI  - Thalidomide salvages lethal hepatic necroinflammation and accelerates recovery
      from cirrhosis in rats.
AB  - BACKGROUND/AIMS: The authors investigated the feasibility of thalidomide employed
      to treat liver fibrosis. METHODS: A cirrhotic model was established using Sprague
      Dawley rats fed thioacetamide. Thalidomide-treated group was given thalidomide
      (10mg/kg/day) intraperitoneally for 10 consecutive days. Mortality,
      histopathological changes, TNFalpha, TGFbeta1, TIMP-1 and TIMP-2 were determined.
      Expression of TNFalpha and TGFbeta1 mRNA of Kupffer's cells derived from the
      experimental rats were determined. RESULTS: The mortality rates of thalidomide
      treated group and vehicle-treated group were 8 and 32%, respectively. The total
      Knodell score of thalidomide-treated rats was lower than those of vehicle-treated
      rats. Micro-nodular cirrhosis resolved grossly in thalidomide-treated rats on day
      28; while vehicle-treated rats continued to display uneven liver surface on day
      28. Expression of TNFalpha, TGFbeta1, TIMP-1, and TIMP-2 was decreased in
      thalidomide-treated rats compared to those treated with vehicles. Finally, the
      expression of TNFalpha and TGFbeta1 mRNA of Kupffer's cells derived from rats
      treated with thalidomide were much lower than those treated with vehicle.
      CONCLUSIONS: Thalidomide salvages lethal hepatic necroinflammation, accelerates
      recovery from cirrhosis in rats, and works by suppressing of TNFalpha and
      TGFbeta1 production of Kupffer's cells.

PMID- 15464242
TI  - Pathogenesis of intracranial hypertension in acute liver failure: inflammation,
      ammonia and cerebral blood flow.
AB  - BACKGROUND/AIMS: The study aims were to determine the role of inflammation in the
      pathogenesis of increased intracranial pressure (ICP) in patients with acute
      liver failure (ALF) and its interplay with cerebral blood flow (CBF) and ammonia.
      METHODS: Twenty-one patients with ALF were studied from the time they were
      ventilated for grade 4 encephalopathy until receiving specific treatment for
      increased ICP. Depending upon the ICP, the patients were divided into two groups;
      those that required specific treatment (ICP>20 mmHg, group 1: n=8, ICP: 32 (28
      54) mmHg); and those that did not (ICP< or =20 mmHg, group 2: n=13, ICP: 15 (10
      20) mmHg). RESULTS: Inflammatory markers, arterial ammonia and CBF were
      significantly higher in the group 1 patients. TNFalpha levels correlated with CBF
      (r=0.80). Four patients from group 2 developed surges of increased ICP (32 (15
      112) hours from enrolment). These were associated increases in markers of
      inflammation and TNFalpha, and an increase in CBF. There was no change in these
      inflammatory markers, CBF or ICP in the other 9 group 2 patients. CONCLUSIONS:
      The results of this study suggest that inflammation plays an important
      synergistic role in the pathogenesis of increased ICP possibly through its
      effects on CBF.

PMID- 15464243
TI  - Increased expression of toll-like receptor 4 enhances endotoxin-induced hepatic
      failure in partially hepatectomized mice.
AB  - BACKGROUND/AIMS: Liver failure associated with infections after hepatectomy
      remains a cause of mortality. It has recently been reported that toll-like
      receptor 4 (TLR4) is involved in recognizing lipopolysaccharides (LPS). The aim
      of this study was to investigate the role of TLR4 in endotoxin-induced liver
      injury after hepatectomy. METHODS: C3H/HeN and C3H/HeJ mice underwent 70%
      hepatectomy or sham surgery, and LPS was administered 48 h after surgery.
      Expression of TLR4 mRNA, nuclear factor-kappaB (NF-kappaB) activation, tumor
      necrosis factor-alpha (TNF-alpha) and serum ALT levels, histological findings,
      and myeloperoxidase content were examined. Survival after LPS administration was
      also determined. RESULTS: Hepatic expression of TLR4 was significantly increased
      6-72 h after hepatectomy. In mice with endotoxemia after hepatectomy, hepatic NF
      kappaB activation was greatly increased. Hepatic mRNA and serum levels of TNF
      alpha, and ALT levels were significantly elevated compared with sham operated
      controls. Focal necrosis with neutrophil infiltration was apparent, which is
      consistent with increased myeloperoxidase contents in endotoxemia after
      hepatectomy in C3H/HeN mice. These were completely absent in C3H/HeJ mice.
      Survival of C3H/HeN mice with endotoxemia after hepatectomy was significantly
      lower than that of C3H/HeJ mice. CONCLUSIONS: Upregulated TLR4 expression and
      function after hepatectomy plays a pivotal role in endotoxin-induced liver injury
      after hepatectomy.

PMID- 15464244
TI  - Overexpression of cortactin is involved in motility and metastasis of
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The molecular basis of the metastasis of hepatocellular
      carcinoma (HCC) is not fully understood. The aim of this study was to elucidate
      the crucial genes involved in metastasis of HCC. METHODS: We compared expression
      profiles among highly metastatic HCC cell lines and non-metastatic HCC cell lines
      by using oligonucleotide array to identify genes associated with metastasis. We
      further investigated the effect of identified gene on cell motility and
      metastasis in vitro and in vivo. Finally, we examined immunohistochemistry in
      human tissue samples. RESULTS: We identified 39 genes whose expression levels
      were significantly correlated with metastatic ability (P<0.05). Of these genes,
      we further investigated cortactin, because this cortical actin-associated protein
      is a substrate of Src, whose activation has been shown to be involved in HCC cell
      migration and metastasis. Overexpression of cortactin in a non-metastatic HCC
      cell line increased cell motility, and resulted in metastasis in an orthotopic
      model. Furthermore, immunohistochemical expression of cortactin revealed its
      significant overexpression in HCC with intrahepatic metastasis compared with HCC
      without intrahepatic metastasis (P<0.005). CONCLUSIONS: Overexpression of
      cortactin may play a role in the metastasis of HCC by influencing cell motility,
      and cortactin could be a sensitive marker for HCC with intrahepatic metastasis.

PMID- 15464245
TI  - Ninjurin1 increases p21 expression and induces cellular senescence in human
      hepatoma cells.
AB  - BACKGROUND/AIMS: Ninjurin1 is a novel adhesion molecule that has a role in
      promoting nerve regeneration. Although ninjurin1 is ubiquitously expressed in
      various human tissues, including the liver, the biologic functions of ninjurin1
      in tissues other than the nervous system remain unknown. The aim of this study
      was to investigate the function of ninjurin1 in hepatocytes. METHODS: The effect
      of ninjurin1 overexpression was examined in Huh-7 hepatoma cells. Ninjurin1
      expression was examined by Western blot in human hepatocellular carcinoma tissues
      as well as their adjacent liver tissues. RESULTS: Ninjurin1-overexpressing clones
      exhibited strong growth inhibition due to G1 cell cycle arrest, which is
      associated with a posttranscriptional increase in p21WAF1/Cip1, a decrease of
      cyclin-dependent kinase 2 activity and the hypophosphorylation of Rb. The
      ninjurin1-overexpressing clones had increased senescence-associated beta
      galactosidase activity and autofluorescent pigment, characteristic features of
      cellular senescence. The levels of ninjurin1 expression were higher in
      hepatocellular carcinoma tissues than those in adjacent liver tissues.
      CONCLUSIONS: The present study provides the first evidence that ninjurin1 is able
      to induce the senescence program. Ninjurin1 may be involved in the regulation of
      cellular senescence in the liver during carcinogenesis.

PMID- 15464246
TI  - Alcohol is an important co-factor for both steatosis and fibrosis in Northern
      Italian patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: Steatosis in patients with chronic hepatitis C (CHC) may be the
      result of both viral and host factors. To evaluate: (1) the relationship between
      steatosis and either host or viral factors; (2) the correlation between steatosis
      and fibrosis in patients with CHC. METHODS: A consecutive series of 349 patients
      were evaluated for steatosis. At liver biopsy, patients were tested for
      virological, and laboratory analysis and questioned for alcohol consumption.
      RESULTS: Logistic regression analysis demonstrated that steatosis was
      independently associated with genotype 3a (odds ratio, OR 3.5), alcohol intake at
      the time of biopsy (OR 2.6) and age >35 years (OR 2.7). In multivariate analysis
      the presence of fibrosis was associated with past alcohol abuse (OR 3.7), and age
      older than 44 years (OR 2.2). Overall, a weak correlation was found between grade
      of steatosis and fibrosis score (r=0.861, P=0.05), which disappeared excluding
      patients without past or current alcohol intake. A direct correlation emerged
      between grade of steatosis and both 'grading' and 'staging' only in patients with
      genotypes other than 3a. CONCLUSIONS: Genotype 3a is the main risk factor for
      steatosis in patients with CHC. The grade of steatosis correlated with both
      grading and staging only in patients with genotypes other than 3a and this
      relationship is strictly linked to alcohol consumption.

PMID- 15464247
TI  - Influence of interleukin 12B (IL12B) polymorphisms on spontaneous and treatment
      induced recovery from hepatitis C virus infection.
AB  - BACKGROUND/AIMS: Interleukin-12 (IL-12) governs the Th1-type immune response,
      affecting the spontaneous and treatment-induced recovery from HCV-infection. We
      investigated whether the IL12B polymorphisms within the promoter region (4 bp
      insertion/deletion) and the 3'-UTR (1188-A/C), which have been reported to
      influence IL-12 synthesis, are associated with the outcome of HCV infection.
      METHODS: We analyzed 186 individuals with spontaneous HCV clearance, 501
      chronically HCV infected patients, and 217 healthy controls. IL12B 3'-UTR and
      promoter genotyping was performed by Taqman-based assays with allele-specific
      oligonucleotide probes and PCR-based allele-specific DNA-amplification,
      respectively. RESULTS: The proportion of IL12B promoter and 3'-UTR genotypes did
      not differ significantly between the different cohorts. However, HCV genotype 1
      infected patients with high baseline viremia carrying the IL12B 3'-UTR 1188-C
      allele showed significantly higher sustained virologic response (SVR) rates
      (25.3% vs. 46% vs. 54.5% for A/A, A/C and C/C) due to reduced relapse rates
      (24.2% vs. 12% vs. zero % for A/A, A/C and C/C). CONCLUSIONS: IL12B 3'-UTR 1188-C
      allele carriers appear to be capable of responding more efficiently to antiviral
      combination therapy as a consequence of a reduced relapse rate. No association of
      IL12B polymorphisms and self-limited HCV infection could be demonstrated.

PMID- 15464248
TI  - Quantification and genotyping of hepatitis B virus in a single reaction by real
      time PCR and melting curve analysis.
AB  - BACKGROUND/AIMS: Both viral titer and genotype of hepatitis B virus (HBV) play
      critical roles in determining clinical outcome and response to antiviral
      treatment in hepatitis B patients. In this study, a method was developed to
      determine both parameters in a single-tube reaction. METHODS: The method contains
      two consecutive steps, the first step used real-time PCR for quantification and
      second step used melting curve analysis for genotyping. For accurate
      quantification, the PCR primers and hybridization probes were selected from
      highly conserved regions to ensure the equivalent amplification and hybridization
      of all genotypes of HBVs. Within the sensor probe there exists signature single
      nucleotide polymorphisms (SNPs), which could effectively differentiate different
      HBV genotypes by showing different melting temperatures. RESULTS: The
      quantification results showed great consistency with the commercial assays in
      linear range from 10(2) to 10(11) copies/ml. By comparison with the traditional
      restriction fragment length polymorphism (RFLP) methods, 99% of samples were
      accurately genotyped by current assay, and with a higher detection rate. In
      addition, this method can detect mixed HBV infections. CONCLUSIONS: Currently,
      this methodology can be applied to areas prevalent with HBV genotypes B and C,
      providing an efficient alternative for clinical diagnosis and large-scaled
      longitudinal studies.

PMID- 15464249
TI  - Interferon-alpha stimulation of liver cells enhances hepatitis delta virus RNA
      editing in early infection.
AB  - BACKGROUND/AIMS: RNA editing controls the formation of hepatitis-delta-antigen-S
      and -L and therefore plays a central role in the hepatitis-delta-virus (HDV) life
      cycle. Editing is catalyzed by the enzyme Adenosine-deaminase-acting-on-RNA1
      (ADAR1) of which two different forms, ADAR1-L and ADAR1-S, exist. As ADAR1-L is
      induced by interferon (IFN)-alpha, we examined the influence of IFN-alpha
      stimulation of host cells on HDV-RNA editing. METHODS: Editing was studied in Huh
      7-cells transfected with HDV-RNA on days 7, 14, 21 and 28 after transfection.
      ADAR1-L mRNA was measured by RT-PCR. RESULTS: IFN-alpha-treatment led to a 5-fold
      higher expression of ADAR1-L and to an increase in editing from 14+/-2% (SD) in
      unstimulated controls to 27+/-4% (SD) on day 7 after transfection. Editing
      further increases over time to the same maximum level of 35% in IFN-alpha-treated
      as well as untreated cells. CONCLUSIONS: By IFN-alpha-stimulation both ADAR1-L
      expression and editing are increased in Huh-7-cells at day 7, and the maximum
      level of edited antigenomes is reached earlier with IFN-alpha-treatment as
      compared to untreated cells. Thus, ADAR1-L appears to be able to increase
      editing, but the HDV genome apparently has an intrinsic negative feed-back
      regulation mechanism that limits editing to roughly a third of the genomes.

PMID- 15464250
TI  - Restoring balance to liver stem cell research.

PMID- 15464251
TI  - Liver autoimmune serology: a consensus statement from the committee for
      autoimmune serology of the International Autoimmune Hepatitis Group.

PMID- 15464252
TI  - Images in Hepatology. Metastatic hepatocellular carcinoma.

PMID- 15464253
TI  - Association of non-alcoholic steatohepatitis without significant fibrosis with
      hepatocellular carcinoma.

PMID- 15464254
TI  - Hepatotoxicity due to a formulation of Ganoderma lucidum (lingzhi).

PMID- 15464255
TI  - Orthotopic liver transplantation and hereditary hemorrhagic telangiectasia: do
      hepatic vascular malformations relapse? A long term follow up study on two
      patients.

PMID- 15464256
TI  - Waldenstrom's macroglobulinemia presenting as new-onset ascites.

PMID- 15464257
TI  - Yin Zhi Huang and other plant-derived preparations: where herbal and molecular
      medicine meet.
AB  - A traditional herbal medicine enhances bilirubin clearance by activating the
      nuclear receptor CAR. Yin Zhi Huang, a decoction of Yin Chin (Artemisia
      capillaris) and three other herbs, is widely used in Asia to prevent and treat
      neonatal jaundice. We recently identified the constitutive androstane receptor
      (CAR, NR1I3) as a key regulator of bilirubin clearance in the liver. Here we show
      that treatment of WT and humanized CAR transgenic mice with Yin Zhi Huang for 3
      days accelerates the clearance of intravenously infused bilirubin. This effect is
      absent in CAR knockout animals. Expression of bilirubin glucuronyl transferase
      and other components of the bilirubin metabolism pathway is induced by Yin Zhi
      Huang treatment of WT mice or mice expressing only human CAR, but not CAR
      knockout animals. 6,7-Dimethylesculetin, a compound present in Yin Chin,
      activates CAR in primary hepatocytes from both WT and humanized CAR mice and
      accelerates bilirubin clearance in vivo. We conclude that CAR mediates the
      effects of Yin Zhi Huang on bilirubin clearance and that 6,7-dimethylesculetin is
      an active component of this herbal medicine. CAR is a potential target for the
      development of new drugs to treat neonatal, genetic, or acquired forms of
      jaundice. [Abstract reproduced by permission of J Clin Invest 2004;113:137-143].

PMID- 15464258
TI  - Treatment of patients with hepatic failure: the difficult place of liver support
      systems.
AB  - Prospective, randomized, multicenter, controlled trial of a bioartificial liver
      in treating acute liver failure. Demetriou AA, Brown RS Jr, Busuttil RW, Fair J,
      McGuire BM, Rosenthal P, Am Esch JS 2nd, Lerut J, Nyberg SL, Salizzoni M, Fagan
      EA, de Hemptinne B, Broelsch CE, Muraca M, Salmeron JM, Rabkin JM, Metselaar HJ,
      Pratt D, De La Mata M, McChesney LP, Everson GT, Lavin PT, Stevens AC, Pitkin Z,
      Solomon BA. Liver Support Unit, Department of Surgery, Cedars-Sinai Medical
      Center, 8700 Beverly Boulevard, Suite 8215, North Tower, Los Angeles, CA 90048,
      USA. OBJECTIVE: The HepatAssist liver support system is an extracorporeal porcine
      hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL
      were evaluated in a prospective, randomized, controlled, multicenter trial in
      patients with severe acute liver failure. SUMMARY BACKGROUND DATA: In
      experimental animals with acute liver failure, we demonstrated beneficial effects
      of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients
      yielded promising results. METHODS: A total of 171 patients (86 control and 85
      BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and
      primary nonfunction following liver transplantation were included. Data were
      analyzed with and without accounting for the following confounding factors: liver
      transplantation, time to transplant, disease etiology, disease severity, and
      treatment site. RESULTS: For the entire patient population, survival at 30 days
      was 71% for BAL versus 62% for control (P=0.26). After exclusion of primary
      nonfunction patients, survival was 73% for BAL versus 59% for control (n=147;
      P=0.12). When survival was analyzed accounting for confounding factors, in the
      entire patient population, there was no difference between the 2 groups (risk
      ratio=0.67; P=0.13). However, survival in fulminant/subfulminant hepatic failure
      patients was significantly higher in the BAL compared with the control group
      (risk ratio=0.56; P=0.048). CONCLUSIONS: This is the first prospective,
      randomized, controlled trial of an extracorporeal liver support system,
      demonstrating safety and improved survival in patients with
      fulminant/subfulminant hepatic failure. [Abstract reproduced by permission of Ann
      Surg 2004;239:660-667; discussion 667-670].

PMID- 15464259
TI  - Age-dependent enhancement of hippocampal long-term potentiation in knock-in mice
      expressing human apolipoprotein E4 instead of mouse apolipoprotein E.
AB  - Human apolipoprotein E (apoE) comprises three isoforms, apoE2, apoE3 and apoE4,
      and apoE4 has been reported as a risk factor of Alzheimer's disease (AD). One of
      the clinical symptoms of AD is disorder of memory that has been suggested to be
      related with synaptic plasticity such as long-term potentiation (LTP). Here, we
      show the enhancement of hippocampal LTP at younger age in knock-in mice lacking
      mouse apoE, but instead expressing human apoE4. The enhancement of LTP in apoE4
      knock-in mice is age-dependent, and it disappears in adult apoE4 knock-in mice.
      In apoE3 knock-in mice LTP is unaltered, thus human apoE4, but not apoE3,
      specifically modulates synaptic plasticity at younger age. Since basal synaptic
      transmission and distribution of glutamate receptors, as well as presynaptic
      functions, are intact in apoE4 knock-in mice, postsynaptic functional
      modification of LTP through lipid homeostasis is suggested. ApoE4 knock-in mice
      would be a useful animal model of human apoE4 carriers, and our finding that LTP
      is enhanced in younger apoE4 knock-in mice is in accord with the previous report
      showing higher intelligence in young human apoE4 carriers.

PMID- 15464260
TI  - On the rhythmicity of quadratic phase coupling in the trace alternant EEG in
      healthy neonates.
AB  - The time-variant quadratic phase coupling (QPC) in trace alternant (TA) EEG
      patterns in healthy full-term neonates (quiet sleep) was investigated by means of
      time-variant bispectral analysis. The frequency plain 1-1.5 Hz <=> 3.5-4.5 Hz was
      used as the region-of-interest. QPC rhythms with a frequency of approximately 0.1
      Hz were found in all neonates (n = 6). It can be demonstrated that the QPC rhythm
      of the TA is generated by a pattern-spanning time-variant phase-locking process
      characterising early functional interactions in the immature brain.

PMID- 15464261
TI  - The tau H2 haplotype is almost exclusively Caucasian in origin.
AB  - We have assessed the distribution of the tau H1/H2 haplotype in the publicly
      available reference series of samples with representatives of most racial groups.
      This analysis shows that the H2 haplotype is probably exclusively Caucasian in
      origin and its marginal occurrence in other racial groups is likely to reflect
      admixture. We discuss this observation in terms of the origin of the H2 haplotype
      and the epidemiology of the tauopathies.

PMID- 15464262
TI  - Upregulation and colocalization of p75 and Nav1.8 in Purkinje neurons in
      experimental autoimmune encephalomyelitis.
AB  - Recent studies have indicated that, in addition to demyelination and axonal
      degeneration, a third factor, dysregulated ion channel expression, contributes to
      the pathophysiology of experimental autoimmune encephalomyelitis (EAE) and
      multiple sclerosis (MS). Consistent with this suggestion, upregulated expression
      of sodium channel Na(v)1.8 is observed in Purkinje neurons in EAE and MS, and
      biophysical studies indicate that aberrant expression of Na(v)1.8 produces
      abnormal Purkinje cell firing which may contribute to the development of
      cerebellar ataxia. However, the molecular mechanisms that contribute to the
      upregulation of Na(v)1.8 in Purkinje cells in EAE and MS have not yet been
      determined. Previous studies have shown that neurotrophic factors can modulate
      sodium channel expression and that elevated levels of NGF are present in EAE and
      MS. Using immunocytochemical methods, we examined the relationship between the
      upregulation of Na(v)1.8 and the expression of the NGF receptors p75 and TrkA in
      EAE. Here we demonstrate that upregulation of Na(v)1.8 is associated with
      expression of p75 and low levels of TrkA in the majority of Purkinje cells in
      EAE. These findings, together with previous studies demonstrating a modulatory
      role of NGF on sodium channel expression, suggest that NGF acting via p75
      contributes to the upregulation of Na(v)1.8 in Purkinje cells in EAE.

PMID- 15464263
TI  - Regulation of neuronal nitric oxide synthase mRNA expression in the rat
      magnocellular neurosecretory system.
AB  - We examined the activation of nNOS mRNA expression within the supraoptic and
      paraventricular nuclei (SON and PVN) of the hypothalamus. In salt-loaded rats
      nNOS mRNA expression was significantly increased in both nuclei. In rats given
      i.p. injections of 1.5 M NaCl (4 ml/kg), a small but significant increase in nNOS
      mRNA expression in the SON and PVN was found 6 h after injection; no change was
      detected 2 or 4 h after injection. In rats in which hyponatraemia had been
      induced experimentally, nNOS mRNA was downregulated in the SON, and expression
      levels were not increased within 4 h after intense acute osmotic stimuli.
      Finally, neurons of the SON were antidromically-activated by neural stalk
      stimulation for 2 h. No increase of nNOS mRNA expression in the SON was observed
      2 h after stimulation. Thus, increased electrical activity is not directly
      coupled to rapidly increased expression of nNOS mRNA, and hence acute increases
      in nNOS mRNA expression are unlikely to play a role in short-term adaptation of
      the magnocellular system to osmotic stimulation.

PMID- 15464264
TI  - Age differences in estimating arrival-time.
AB  - The present study examined the accuracy in extrapolating an occluded trajectory
      in relation to observer age. Adults and children aged 7, 10, and 13 were tested
      in a prediction-motion task which consisted of judging, after the occlusion of
      the final part of its path, the moment of arrival of a moving stimulus towards a
      specified position. Results showed that children as young as 7 years old are able
      to use the same strategy as adults in the extrapolation of an occluded moving
      object. However, accuracy in responses improves most significantly for occlusion
      times equal to or more than 400 ms and this improvement occurs mainly between 7
      and 10 years of age. This confirms that children are less efficient in performing
      the computations necessary to extrapolate in time an occluded trajectory.

PMID- 15464265
TI  - Regulation of tyrosine hydroxylase gene transcription by Sry.
AB  - Testes determining factor Sry is encoded by the Sry locus on the Y chromosome and
      may be involved in the regulation of blood pressure. Here we tested the
      hypothesis that Sry regulates transcription of tyrosine hydroxylase (TH), the
      rate-limiting enzyme in the biosynthesis of catecholamines. Sry was found to be
      expressed in catecholaminergic regions, in male but not female rats. Co
      transfection of PC12 cells with expression vector for Sry and the reporter
      construct [p5'TH(-773/+27)/Luc], containing 773 of the proximal nucleotides of
      the TH promoter directing luciferase reporter activity, led to elevation of
      reporter activity. The reporter activity of a shorter construct [p5'TH(
      272/+27)/Luc] lacking putative Sry sites also responded to Sry. However, mutation
      of the AP1 site in the TH promoter greatly reduced induction by Sry, indicating
      that the regulation is primarily at this motif. The remaining, significantly
      increased expression with the mutated TH promoter construct may reflect Sry
      function at other sites in addition to the AP1 motif. These results reveal that
      Sry can regulate TH transcription and suggest that this may be one of the
      mechanisms of Sry mediated regulation of catecholamine biosynthesis in
      catecholaminergic neurons in males.

PMID- 15464266
TI  - Methamidophos transiently inhibits neuronal nicotinic receptors of rat substantia
      nigra dopaminergic neurons via open channel block.
AB  - The use of acetylcholinesterase (AChE) inhibitors is the primary therapeutic
      strategy in the treatment of Alzheimer's disease. However, these drugs have been
      reported to have effects beyond the simple stimulation of neuronal acetylcholine
      receptors (AChRs) by elevated acetylcholine (ACh), interfering directly with the
      nAChR. Therefore, a pure pharmacological blockade of AChE is not usually
      obtained. In this study, the patch-clamp technique was utilized to determine the
      effects of methamidophos, a pesticide that is considered a selective AChE
      inhibitor, on nAChRs of substantia nigra dopaminergic neurons. In spite of the
      fact that methamidophos has been reported to be devoid of direct nicotinic
      actions, our main observation was that it selectively and reversibly blocked
      nAChR responses, without directly affecting the holding current. Methamidophos
      produced a downward shift in the dose response curve for nicotine; the mechanism
      accounting for this non-competitive antagonism was open channel block, in view of
      its voltage dependence. Pre-treatment with vesamicol did not prevent the
      reduction of nicotine-induced currents, indicating that the effect on nAChRs was
      independent from the activity of methamidophos as a cholinesterase inhibitor. Our
      results conclude that methamidophos has a complex blocking action on neuronal
      nAChRs that is unlinked to the inhibition of AChE. Therefore, it should not be
      considered a selective AChE inhibitor and part of its toxic effects could reside
      in an interference with the nicotinic neurotransmission.

PMID- 15464267
TI  - Position coding in a video-controlled pointing task with a rotated visual
      display: evidence for individual differences in visuo-proprioceptive interaction.
AB  - In video-controlled tasks, visuomotor performance is generally initially poor
      with rotated visual display, but improves through trial-by-trial learning. We
      hypothesise that the inaccurate processing of the visual hand-to-target vector
      mainly results from the persistent influence of non-visual information relating
      to arm posture. To test this hypothesis, arm-related proprioceptive and visual
      information were independently manipulated in a video-controlled pointing task.
      Analysis of movement vectors revealed that the target was located according to
      the visual hand but its proprioceptive orientation (Allelocentric(1) system of
      reference, N = 10), or according to the proprioceptive hand location and
      orientation (Egocentric system of reference, N = 8). The prevalence of one system
      of reference correlated with the accuracy of proprioceptive signals informing
      about arm posture. One obstacle in mastering video-controlled task results thus
      from the persistent influence of proprioceptive information in the spatial coding
      of visual goals for action, which however differs across individuals.

PMID- 15464268
TI  - Possible association of mitochondrial transcription factor A (TFAM) genotype with
      sporadic Alzheimer disease.
AB  - Mitochondrial transcription factor A (TFAM) is essential for transcription and
      replication of mammalian mitochondrial DNA (mtDNA). Disturbance of maintenance of
      mtDNA integrity or mitochondrial function may underlay neurodegenerative
      disorders such as Alzheimer disease (AD). TFAM, the gene encoding TFAM maps to
      chromosome 10q21.1, a region that showed linkage to late-onset AD in several
      study samples. We screened TFAM for single nucleotide polymorphisms (SNPs) and
      genotyped the G>C SNP rs1937, coding for S12T in mitochondrial signal sequence of
      TFAM, and the A>G SNP rs2306604 (IVS4+113A>G) in 372 AD patients and 295
      nondemented control subjects. There was an association of genotype rs1937G/G with
      AD in females and an association of a TFAM haplotype with AD both in the whole
      sample and in females. The findings suggest that a TFAM haplotype containing
      rs1937 G (for S12) may be a moderate risk factor for AD.

PMID- 15464269
TI  - Astrocytic and neuronal biochemical markers in the sera of subjects with diabetes
      mellitus.
AB  - To determine if clinical diabetes is associated with disruption of the blood
      brain barrier (BBB) and/or brain injury, enzyme-linked immunoassays and Western
      blots were used to measure serum levels of S100B, NSE and their auto-antibodies
      in type 1 and type 2 diabetic subjects. Serum S100B concentrations in type 2
      diabetic subjects, but not in type 1 diabetic subjects, were significantly lower
      than those found in healthy controls. There were no significant differences in
      serum NSE levels of either type 1 or type 2 diabetics compared to healthy
      controls. However, there was a significant increase in antibodies to NSE in both
      type 1 and type 2 diabetic subjects compared to controls, whereas diabetics and
      controls had equally very low levels of anti S100B auto-antibodies. These studies
      suggest that diabetes in humans may be associated with alterations in the BBB
      integrity that allow the emergence of antibodies against neuronal antigens.

PMID- 15464270
TI  - Association of DAAO with schizophrenia in the Chinese population.
AB  - Recently, the gene called DAAO was reported to be associated with schizophrenia
      in the French Canadian populations. Here, we report a result obtained in the
      study of our large collection of 547 schizophrenia cases and 536 controls in the
      Chinese population. Six single-nucleotide polymorphisms (SNPs) were genotyped at
      and around the DAAO locus, covering a 10-kb region entirely encompassing the
      complementary DNA sequences of DAAO. We found statistically significant
      differences in allele distributions on one marker: SNP rs3741775 (P = 0.0000001).
      In the haplotype analysis based on the information of linkage-disequilibrium
      block across this gene locus, we demonstrated a highly significant association
      between schizophrenia and a DAAO haplotype (P = 2.0173 x 10(-21)), which
      therefore provides an independent statistical support for association of the DAAO
      gene with schizophrenia and indicates that the DAAO gene may play a significant
      role in the etiology of schizophrenia in the Han Chinese.

PMID- 15464271
TI  - Acupuncture-mediated inhibition of ethanol-induced dopamine release in the rat
      nucleus accumbens through the GABAB receptor.
AB  - Clinical trials are currently underway to determine the effectiveness of
      acupuncture in the treatment of drug abuse. However, there are still many
      unanswered questions about the basic mechanisms of acupuncture. Studies have
      shown that the GABA(B) receptor system may play a significant modulatory role in
      the mesolimbic system in drug abuse, including ethanol. The in vivo microdialysis
      study was designed to investigate the effect of acupuncture on acute ethanol
      induced dopamine release in the nucleus accumbens and the potential role of the
      GABA(B) receptor system in acupuncture. Male Sprague-Dawley rats were
      administered with the highly selective GABA(B) antagonist SCH 50911 (3 mg/kg,
      i.p.) 1h prior to an intraperitoneal injection of ethanol (1 g/kg). Immediately
      after ethanol treatment, acupuncture was given at bilateral Shenmen (HT7) points
      for 1min. Acupuncture at the specific acupoint HT7, but not at control points
      (PC6 or tail) significantly decreased dopamine release in the nucleus accumbens.
      Inhibition of dopamine release by acupuncture was completely prevented by SCH
      50911. These results suggest that stimulation of specific acupoints inhibits
      ethanol-induced dopamine release by modulating GABA(B) activity and imply that
      acupuncture may be effective in blocking the reinforcing effects of ethanol.

PMID- 15464272
TI  - Crossed-withdrawal reflex in a rat model of neuropathic pain: implications in
      neural plasticity.
AB  - Recently we developed a neuropathic rat model employing a distal sciatic nerve
      branch injury, in which rats show vigorous behavioral signs of neuropathic pain.
      This study was performed to evaluate the crossed-withdrawal reflex in which any
      stimuli applied to the uninjured side produces allodynic signs on the injured
      side in our neuropathic pain model. Rats that received neuropathic surgery
      developed behavioral signs of neuropathic pain. In addition, these rats developed
      pain responses of the injured paw to stimuli applied to the contralateral
      uninjured paw, therefore, demonstrating 'the crossed-withdrawal reflex.'
      Moreover, electrical stimulation of the uninjured paw developed evoked potentials
      in the ventral root on the injured side. These results suggest that information
      processing from input on the uninjured side to output on the injured side, can be
      facilitated in rats with a nerve injury and that neuroplasticity may contribute
      to the crossed-withdrawal reflex.

PMID- 15464273
TI  - Intracerebroventricularly administered galanin does not alter operant reaction
      time or differentially reinforced high rate schedule operant responding in rats.
AB  - Galanin (Gal) is a 29/30 amino acid neuroendocrine peptide that impairs learning
      and memory processes, stimulates feeding, and modulates somatosensory, sex, and
      stress responses. Anatomical markers for Gal are found throughout the brain,
      including in the caudate-putamen and substantia nigra motor regions. Many of the
      behavioral tests that have been used to study the involvement of Gal in complex
      behavioral processes are motorically demanding, but no research has specifically
      investigated the involvement of Gal in response initiation or the maintenance of
      fine motor action. Therefore, the present study examined the effects of
      intraventricularly administered Gal on two highly sensitive operant tasks
      designed to detect alteration of these response properties. Response initiation
      was studied using a light-dark discrimination reaction time task that required a
      correct response within 2.5s of a spatially and temporally uncertain stimulus
      onset. The ability to perform high local rates of responding was studied using an
      operant differential reinforcement of high rate (DRH) of responding task. Gal (10
      20 microg, i.c.v.) did not alter reaction time or inter-response time
      distributions in either task, though did substantially reduce the total number of
      responses and reinforcers obtained on the DRH schedule. These results are
      consistent with a Gal-induced reduction of reinforcer efficacy rather than Gal
      disruption of response initiation or response patterning.

PMID- 15464274
TI  - Thimerosal decreases TRPV1 activity by oxidation of extracellular sulfhydryl
      residues.
AB  - TRPV1, a receptor for capsaicin, plays a key role in mediating thermal and
      inflammatory pain. Because the modulation of ion channels by the cellular redox
      state is a significant determinant of channel function, we investigated the
      effects of sulfhydryl modification on the activity of TRPV1. Thimerosal, which
      oxidizes sulfhydryls, blocked the capsaicin-activated inward current (I(cap)) in
      cultured sensory neurons, in a reversible and dose-dependent manner, which was
      prevented by the co-application of the reducing agent, dithiothreitol. Among the
      three cysteine residues of TRPV1 that are exposed to the extracellular space, the
      oxidation-induced effect of thimerosal on I(cap) was blocked only by a point
      mutation at Cys621. These results suggest that the modification of an
      extracellular thiol group can alter the activity of TRPV1. Consequently, we
      propose that such a modulation of the redox state might regulate the
      physiological activity of TRPV1.

PMID- 15464275
TI  - Recovery after chronic stress fails to reverse amygdaloid neuronal hypertrophy
      and enhanced anxiety-like behavior.
AB  - The hippocampus and amygdala are important components of the neural circuitry
      mediating stress responses. While structural plasticity in the hippocampus may
      mediate cognitive aspects of behavioral impairments caused by severe stress,
      changes in the amygdala are more likely to contribute to the affective aspects of
      stress disorders. Recent reports have identified cellular and molecular
      correlates of stress-induced amygdaloid plasticity that may underlie anxiety.
      Hence, we examined the impact of chronic stress, in terms of its duration, at the
      cellular and behavioral levels in rats. We found that, even after 21 days of
      stress-free recovery, animals exposed to chronic immobilization stress (CIS)
      continue to exhibit enhanced anxiety, as manifested by a significant reduction in
      open-arm exploration and risk-assessment behavior in the elevated plus-maze. At
      the cellular level, we tested if CIS-induced dendritic remodeling in the amygdala
      is also as long-lasting as enhanced anxiety after 21 days of recovery. Indeed,
      long-lasting facilitation of CIS-induced anxiety is accompanied by a persistent
      increase in dendritic arborization of basolateral amygdala (BLA) spiny neurons.
      Moreover, CIS-induced BLA hypertrophy is distinct from hippocampal CA3 atrophy,
      which is reversible within the same period of stress-free recovery. These
      findings on persistent dendritic remodeling in the amygdala, in addition to
      highlighting important differences with hippocampal structural plasticity, may
      provide a cellular basis for examining anxiety and mood disorders triggered by
      chronic stress.

PMID- 15464276
TI  - Social stress and corticosterone regionally upregulate limbic N-methyl-D
      aspartatereceptor (NR) subunit type NR(2A) and NR(2B) in the lizard Anolis
      carolinensis.
AB  - Social aggression in the lizard Anolis carolinensis produces dominant and
      subordinate relationships while elevating corticosterone levels and monoaminergic
      transmitter activity in hippocampus (medial and mediodorsal cortex). Adaptive
      social behavior for dominant and subordinate male A. carolinensis is learned
      during aggressive interaction and therefore was hypothesized to involve
      hippocampus and regulation of N-methyl-d-aspartate (NMDA) receptors. To test the
      effects of social stress and corticosterone on NMDA receptor subunits (NR), male
      lizards were either paired or given two injections of corticosterone 1 day apart.
      Paired males were allowed to form dominant-subordinate relationships and were
      killed 1 day later. Groups included isolated controls, dominant males,
      subordinate males and males injected with corticosterone. Brains were processed
      for glutamate receptor subunit immunohistochemistry and fluorescence was analyzed
      by image analysis for NR(2A) and NR(2B) in the small and large cell divisions of
      the medial and mediodorsal cortex. In the small granule cell division there were
      no significant differences in NR(2A) or NR(2B) immunoreactivity among all groups.
      In contrast, there was a significant upregulation of NR(2A) and NR(2B) subunits
      in the large pyramidal cell division in all three experimental groups as compared
      with controls. The results revealed significantly increased NR(2A) and NR(2B)
      subunits in behaving animals, whereas animals simply injected with corticosterone
      showed less of an effect, although they were significantly increased over
      control. Upregulation of NR(2) subunits occurs during stressful social
      interactions and is likely to be regulated in part by glucocorticoids. The data
      also suggest that learning social roles during stressful aggressive interactions
      may involve NMDA receptor-mediated mechanisms.

PMID- 15464277
TI  - Expression of the secreted factors noggin and bone morphogenetic proteins in the
      subependymal layer and olfactory bulb of the adult mouse brain.
AB  - The antagonism between noggin and the bone morphogenetic proteins (BMPs) plays a
      key role during CNS morphogenesis and differentiation. Recent studies indicate
      that these secreted factors are also widely expressed in the postnatal and adult
      mammalian brain in areas characterized by different types of neural plasticity.
      In particular, significant levels of noggin and BMP expression have been
      described in the rodent olfactory system. In the mammalian forebrain, the
      olfactory bulb (OB) and associated subependymal layer (SEL) are documented as
      sites of adult neurogenesis. Here, using multiple approaches, including the
      analysis of noggin-LacZ heterozygous mice, we report the expression of noggin and
      two members of the BMP family, BMP4 and BMP7, in these regions of the adult
      mammalian forebrain. We observe that along the full extent of the SEL, from the
      lateral ventricle to the olfactory bulb, noggin and BMP4 and 7 are mainly
      associated with the astrocytic glial compartment. In the OB, BMP4 and 7 proteins
      remain primarily associated with the SEL while strong noggin expression was also
      found in cells located in different OB layers (i.e. granule, external plexiform,
      glomerular layers). Taken together our data lead us to hypothesize that within
      the SEL the antagonism between noggin and BMPs, both produced by the glial tubes,
      act through autocrine/paracrine inductive mechanisms to maintain a neurogenetic
      environment all the way from the lateral ventricle to the olfactory bulb. In the
      OB, their expression patterns suggest multiple regulatory roles on the unusual
      neural plasticity exhibited by this region.

PMID- 15464279
TI  - Galectin-1 expression correlates with the regenerative potential of rubrospinal
      and spinal motoneurons.
AB  - Axotomized spinal motoneurons are able to regenerate to their peripheral targets,
      whereas injured rubrospinal neurons that lie completely within the CNS fail to
      regenerate. The differing cell body reactions to axotomy of these two neuronal
      populations have been implicated in their disparate regenerative ability.
      Recently, the lectin galectin-1 has been shown to be involved in both spinal
      motoneurons and primary afferent regeneration. Using in situ hybridization, we
      compared the endogenous galectin-1 mRNA expression in spinal motoneurons and
      rubrospinal neurons after axotomy. We found that 7 and 14 days after axotomy,
      galectin-1 mRNA increased in spinal motoneurons but decreased in rubrospinal
      neurons. Infusion of the brain-derived neurotrophic factor into the vicinity of
      the injured rubrospinal nucleus, which we have previously shown to increase the
      regenerative capacity of rubrospinal neurons, significantly increased galectin-1
      mRNA compared with uninjured control levels. Thus, the expression of galectin-1
      in neurons correlates with the regenerative propensity.

PMID- 15464278
TI  - Cooperation in signal transduction of extracellular guanosine 5' triphosphate and
      nerve growth factor in neuronal differentiation of PC12 cells.
AB  - Guanosine 5' triphosphate (GTP), acting synergistically with the nerve growth
      factor (NGF), enhances the proportion of neurite-bearing cells in cultures of
      PC12 rat pheochromocytoma cells. We studied the transduction mechanisms activated
      by GTP in PC12 cells and found that addition of GTP (100 microM) increased
      intracellular calcium concentration ([Ca(2+)](i)) in cells that were between 60
      and 70% confluent. Addition of GTP also enhanced activation of NGF-induced
      extracellular regulated kinases (ERKs) and induced Ca(2+) mobilization. This
      mobilization, due to the activation of voltage-sensitive and ryanodine-sensitive
      calcium channels, as well as pertussis toxin-sensitive purinoceptors, modulates
      Ca(2+)-activated K(+) channels not involved in activation of ERKs. The results
      presented here indicate that GTP-triggered [Ca(2+)](i) increase may be a key
      event in GTP signal transduction, which can modulate activity of ERKs. The
      physiological importance of the GTP effect lies in its capacity to interact with
      the NGF-activated pathway to enhance neurite outgrowth from PC12 cells.

PMID- 15464280
TI  - Ascorbate modulates pentylenetetrazol-induced convulsions biphasically.
AB  - Ascorbate is an antioxidant vitamin that is found in high concentrations in the
      brain which seems to have neuroprotective properties in some experimental models
      of excitotoxic neurological disorders, including convulsive behavior and reactive
      species-related damage. In this study we tested whether ascorbate (30, 100 or 300
      mg/kg, i.p.) protects against the convulsions, protein carbonylation and
      inhibition of Na(+),K(+)-ATPase activity induced by pentylenetetrazol (PTZ; 1.8
      micromol/striatum), a classical convulsant agent that has been fairly used for
      the study of epilepsy and screening of new compounds with antiepileptic activity.
      The intrastriatal injection of PTZ caused convulsive behavior in a dose-dependent
      manner and an increase in the total protein carbonyl content of the injected
      striatum. However, duration of PTZ-induced convulsive episodes did not correlate
      with protein carbonyl content of the injected striatum. Ascorbate, at high doses
      (300 mg/kg), protected against PTZ-induced convulsions, protein carbonylation and
      inhibition of Na(+),K(+)-ATPase activity in the rat striatum, further suggesting
      a anticonvulsant and neuroprotective role for this vitamin. Conversely,
      intermediate doses of ascorbate (100 mg/kg) potentiated the duration of the
      convulsive episodes, but had no additive effects on protein carbonylation or
      Na(+),K(+)-ATPase activity inhibition induced by PTZ. Low doses of ascorbate (30
      mg/kg) prevented PTZ-induced increase of total striatal carbonyl protein content,
      but did not alter PTZ-induced convulsions and Na(+),K(+)-ATPase activity
      inhibition. Collectively, these data indicate that the anticonvulsant activity of
      ascorbate is not related to its antioxidant action and support a dual role for
      this compound as a neuroprotective agent, since while it protects against PTZ
      induced cellular oxidative damage, it has a biphasic effect on PTZ-induced
      convulsions.

PMID- 15464281
TI  - Na(+) and Ca(2+) homeostasis pathways, cell death and protection after oxygen
      glucose-deprivation in organotypic hippocampal slice cultures.
AB  - Intracellular ATP supply and ion homeostasis determine neuronal survival and
      degeneration after ischemic stroke. The present study provides a systematic
      investigation in organotypic hippocampal slice cultures of the influence of
      experimental ischemia, induced by oxygen-glucose-deprivation (OGD). The pathways
      controlling intracellular Na(+) and Ca(2+) concentration ([Na(+)](i) and
      [Ca(2+)](i)) and their inhibition were correlated with delayed cell death or
      protection. OGD induced a marked decrease in the ATP level and a transient
      elevation of [Ca(2+)](i) and [Na(+)](i) in cell soma of pyramidal neurons. ATP
      level, [Na(+)](i) and [Ca(2+)](i) rapidly recovered after reintroduction of
      oxygen and glucose. Pharmacological analysis showed that the OGD-induced
      [Ca(2+)](i) elevation in neuronal cell soma resulted from activation of both N
      methyl-d-aspartate (NMDA)-glutamate receptors and Na(+)/Ca(2+) exchangers, while
      the abnormal [Na(+)](i) elevation during OGD was due to Na(+) influx through
      voltage-dependent Na(+) channels. In hippocampal slices, cellular degeneration
      occurring 24 h after OGD, selectively affected the pyramidal cell population
      through apoptotic and non-apoptotic cell death. OGD-induced cell loss was
      mediated by activation of ionotropic glutamate receptors, voltage-dependent Na(+)
      channels, and both plasma membrane and mitochondrial Na(+)/Ca(2+) exchangers.
      Thus, we show that neuroprotection induced by blockade of NMDA receptors and
      plasma membrane Na(+)/Ca(2+) exchangers is mediated by reduction of Ca(2+) entry
      into neuronal soma, whereas neuroprotection induced by blockade of AMPA/kainate
      receptors and mitochondrial Na(+)/Ca(2+) exchangers might result from reduced
      Na(+) entry at dendrites level.

PMID- 15464282
TI  - Polyamines increase in sympathetic neurons and non-neuronal cells after axotomy
      and enhance neurite outgrowth in nerve growth factor-primed PC12 cells.
AB  - Following axonal damage, sympathetic neurons are capable of regenerating and
      reinnervating their target tissues. Some years ago exogenous administration of
      polyamines was shown to enhance this regeneration. Recently, it was found that
      axonal injury leads to a dramatic up-regulation of the expression of arginase I
      in sympathetic neurons. This enzyme catalyzes the conversion of arginine to
      ornithine, which can subsequently be converted to the diamine putrescine and,
      ultimately, to the polyamines spermidine and spermine. In the present study,
      using an antiserum that reacts with both spermidine and spermine, we have found
      an increase in polyamine levels in both neurons and non-neuronal cells in the
      superior cervical ganglion 2 and 5 days following transection of the ganglion's
      postganglionic trunks. Using PC12 cells primed with nerve growth factor and then
      stripped off the culture dish and replated as a model system for axotomized
      sympathetic neurons, we found that spermidine treatment, with or without nerve
      growth factor, resulted in an increased percentage of cells with a neurite whose
      length was at least twice the diameter of the neuron's cell body. These increases
      could be seen within 48 h and were still evident after 8 days. Together, these
      data support the possibility that endogenous polyamines are involved in the
      normal regeneration which occurs following sympathetic axonal damage.

PMID- 15464283
TI  - Aspartate release from rat hippocampal synaptosomes.
AB  - Certain excitatory pathways in the rat hippocampus can release aspartate along
      with glutamate. This study utilized rat hippocampal synaptosomes to characterize
      the mechanism of aspartate release and to compare it with glutamate release.
      Releases of aspartate and glutamate from the same tissue samples were quantitated
      simultaneously. Both amino acids were released by 25 mM K(+), 300 microM 4
      aminopyridine (4-AP) and 0.5 and 1 microM ionomycin in a predominantly Ca(2+)
      dependent manner. For a roughly equivalent quantity of glutamate released,
      aspartate release was significantly greater during exposure to elevated [K(+)]
      than to 4-AP and during exposure to 0.5 than to 1 microM ionomycin. Aspartate
      release was inefficiently coupled to P/Q-type voltage-dependent Ca(2+) channels
      and was reduced by KB-R7943, an inhibitor of reversed Na(+)/Ca(2+) exchange. In
      contrast, glutamate release depended primarily on Ca(2+) influx through P/Q-type
      channels and was not significantly affected by KB-R7943. Pretreatment of the
      synaptosomes with tetanus toxin and botulinum neurotoxins C and F reduced
      glutamate release, but not aspartate release. Aspartate release was also
      resistant to bafilomycin A(1), an inhibitor of vacuolar H(+)-ATPase, whereas
      glutamate release was markedly reduced. (+/-) -Threo-3-methylglutamate, a non
      transportable competitive inhibitor of excitatory amino acid transport, did not
      reduce aspartate release. Niflumic acid, a blocker of Ca(2+)-dependent anion
      channels, did not alter the release of either amino acid. Exogenous aspartate and
      aspartate recently synthesized from glutamate accessed the releasable pool of
      aspartate as readily as exogenous glutamate and glutamate recently synthesized
      from aspartate accessed the releasable glutamate pool. These results are
      compatible with release of aspartate from either a vesicular pool by a "non
      classical" form of exocytosis or directly from the cytoplasm by an as-yet
      undescribed Ca(2+)-dependent mechanism. In either case, they suggest aspartate is
      released mainly outside the presynaptic active zones and may therefore serve as
      the predominant agonist for extrasynaptic N-methyl-D-aspartate receptors.

PMID- 15464285
TI  - Astrocytes in injured adult rat spinal cord may acquire the potential of neural
      stem cells.
AB  - It has been well documented that in adult rats astrocytes in the subventricular
      zone and subgranular layer of the dentate gyrus are neural stem cells. Elsewhere
      in the CNS astrocytes are not generally recognized as stem cells. Here we
      describe nestin expression in a population of astrocytes in the spinal cord of
      adult rat following cord injury. In either hemitransectioned or longitudinally
      cut spinal cord, there was widespread nestin expression in astrocytes of both the
      gray and white matters. Isolation of the lateral part of the spinal cord from the
      central canal region, where stem cells may reside, could not block the appearance
      of nestin-immunoreactive astrocytes in the lateral cord, and none of them showed
      Fast DiI labeling after the central canal ependyma had been labeled by the dye,
      indicating that the nestin-immunoreactive astrocytes can evolve locally in the
      lateral cord. They were found to be undergoing a process of de-differentiation.
      Culture of the nestin-immunoreactive astrocytes of the lateral cord generated
      neurospheres, the cells of which had the ability of self-renewal, and were able
      to differentiate into neurons, astrocytes, or oligodendrocytes. Taken together,
      the results indicate that the astrocytes in injured adult rat spinal cord may
      acquire the potential of neural stem cells.

PMID- 15464284
TI  - Alterations of N-ethylmaleimide-sensitive atpase following transient cerebral
      ischemia.
AB  - Neuronal repair following injury requires recruitment of large amounts of
      membranous proteins into synaptic and other cell membranes, which is carried out
      by the fusion of transport vesicles to their target membranes. A critical
      molecule responsible for assemblage of membranous proteins is N-ethylmaleimide
      sensitive factor (NSF) which is an ATPase. To study whether NSF is involved in
      ischemic neurological deficits and delayed neuronal death, we investigated
      alterations of NSF after transient cerebral ischemia by means of biochemical
      methods, as well as confocal and electron microscopy. We found that transient
      cerebral ischemia induced depletion of free NSF and concomitantly relocalization
      of NSF into the Triton X-100-insoluble fraction including postsynaptic densities
      in CA1 neurons during the postischemic period. The NSF alterations are
      accompanied by accumulation of large quantities of intracellular vesicles in CA1
      neurons that are undergoing delayed neuronal death after transient cerebral
      ischemia. Therefore, permanent depletion of free NSF and relocalization of NSF
      into the Triton X-100-insoluble fraction may disable the vesicle fusion machinery
      necessary for repair of synaptic injury, and ultimately leads to synaptic
      dysfunction and delayed neuronal death in CA1 neurons after transient cerebral
      ischemia.

PMID- 15464286
TI  - Molecular profiling indicates avian branchiomotor nuclei invade the hindbrain
      alar plate.
AB  - It is generally believed that the spinal cord and hindbrain consist of a motor
      basal plate and a sensory alar plate. We now have molecular markers for these
      territories. The relationship of migrating branchiomotor neurons to molecularly
      defined alar and basal domains was examined in the chicken embryo by mapping the
      expression of cadherin-7 and cadherin-6B, in comparison to genetic markers for
      ventrodorsal patterning (Otp, Pax6, Pax7, Nkx2.2, and Shh) and motoneuron
      subpopulations (Phox2b and Isl1). We show cadherin-7 is expressed in a complete
      radial domain occupying a lateral region of the hindbrain basal plate. The
      cadherin-7 domain abuts the medial border of Pax7 expression; this common limit
      defines, or at least approximates, the basal/alar boundary. The hindbrain
      branchiomotor neurons originate in the medial part of the basal plate, close to
      the floor plate. Their cadherin-7-positive axons grow into the alar plate and
      exit the hindbrain close to the corresponding afferent nerve root. The cadherin-7
      positive neuronal cell bodies later translocate laterally, following this axonal
      trajectory, thereby passing through the cadherin-7-positive basal plate domain.
      Finally, the cell bodies traverse the molecularly defined basal/alar boundary and
      move into positions within the alar plate. After the migration has ended, the
      branchiomotor neurons switch expression from cadherin-7 to cadherin-6B. These
      findings demonstrate that a specific subset of primary motor neurons, the
      branchiomotor neurons, migrate into the alar plate of the chicken embryo.
      Consequently, the century-old concept that all primary motor neurons come to
      reside in the basal plate should be revised.

PMID- 15464287
TI  - Developmental stage-dependent modulation of synapses by postsynaptic expression
      of activated calcium/calmodulin-dependent protein kinase II.
AB  - In Drosophila neuromuscular junctions, there is a unique system which consists of
      two neighboring muscles (M6 and M7) innervated by the same neurons and a gene of
      interest can be expressed in only M6 or in both muscles by GAL4-upstream
      activating sequence expression system. By using this system, we previously
      demonstrated that expression of activated calcium/calmodulin-dependent protein
      kinase II (CaMKII) in the muscle cell promotes coordinated maturation of pre- and
      postsynaptic sites of larvae just after hatching (JAH larvae) in a synapse
      specific manner. Here we show that the promotive effects are no longer seen in
      the older larvae, 8-10 h after hatching (8 h AH larvae). Morphological studies
      indicate that CaMKII activation in fact reduces postsynaptic sites at 8 h AH.
      This is opposite to the effect observed in JAH larvae. These results suggest that
      the mode of CaMKII function switches during development, and that regulation of
      postsynaptic CaMKII activity is necessary for normal synaptic development.
      Finally, we report that in 8 h AH but not in JAH larvae, synapses on M7, in which
      CaMKII activity is not manipulated, are affected by the expression of activated
      CaMKII in M6. This suggests the interesting possibility that at certain
      developmental stages only, modification of synapses on one target cell can
      influence the synapses on another target cell innervated by the same neurons.

PMID- 15464288
TI  - Adult neural stem cells from the mouse subventricular zone are limited in
      migratory ability compared to progenitor cells of similar origin.
AB  - The subventricular zone (SVZ) in the forebrain is the largest source of neural
      stem cells and progenitor cells in the adult CNS. To assess the ability of adult
      neural stem cells to survive, differentiate and migrate, we have compared the
      behavior of dissociated, neurosphere-derived stem cells with that of progenitor
      cells in transplantation experiments. This ability was first tested in vivo,
      offering the stem cells the possibility to migrate along the rostral migratory
      stream (RMS), their specific pathway. In addition, the differential behaviors of
      the two classes of cells were also compared in vitro by grafting them into
      organotypic slice cultures containing either tangential (embryonic cerebral
      cortex) or radial (early postnatal cerebellar cortex) migratory routes. Most of
      the grafted adult neurosphere-derived stem cells survived and integrated in vivo,
      and a proportion of them differentiate into neurons, oligodendrocytes or
      astrocytes. However, they were unable to migrate along the RMS and remained in
      the vicinity of the injection site. In contrast, SVZ progenitor cells were able
      to migrate toward the olfactory bulb and, once there, to acquire the phenotype of
      granule cells, as previously reported. In vitro, neural stem cells exhibited a
      better migratory ability, although they only migrated for short distances,
      particularly, in forebrain slices. Nevertheless, the average distance covered by
      progenitor cells was a two-fold longer than that covered by neural stem cells,
      corroborating that this class of more specified cells has higher migratory
      ability. These results suggest that the in vitro conditions of expanding SVZ
      derived stem cells, required to maintain them in an immature stage might modify
      their intrinsic properties, preventing their differentiation into neuroblasts and
      their subsequent migration.

PMID- 15464289
TI  - Spaceflight alters the fiber composition of the aortic nerve in the developing
      rat.
AB  - Hydrostatic pressure gradients due to the gravitational force in blood vessels
      disappear under conditions of microgravity during spaceflight, and the ability of
      the baroreceptor reflex to control arterial pressure and blood distribution may
      be altered. We hypothesized, on the basis of the results obtained in our previous
      experiments using the head-down tilt method in rats and rabbits, that the range
      of increase in arterial pressure caused by animal behavior narrows under
      conditions of microgravity, affecting the development of high-threshold
      unmyelinated fibers in the rat aortic nerve which sends signals from
      baroreceptors located in the aortic wall to the reflex center. We verified this
      hypothesis using 9-day-old rat neonates housed with their dams for 16 days on the
      space shuttle Columbia in outer space (STS-90, Neurolab Mission). Age-matched
      neonatal rats with the dams remained on the ground as controls. After breeding
      was carried out in the three experimental groups (FLT, spaceflight; AGC,
      asynchronous ground control; VIV, vivarium ground control), specimens of the 25
      day-old rats were excised and five left aortic nerves in each group were examined
      by electron microscopy. The number of aortic unmyelinated fibers was
      significantly less in the FLT group than in each ground control (mean+/-S.D.;
      139+/-37 in the FLT, 207+/-36 in the AGC, 283+/-121 in the VIV; P<0.05), which
      may be related to the weakness of the baroreceptor reflex under conditions of
      microgravity in space. This result may contribute to understanding of the several
      cardiovascular issues which occur under microgravity and after reexposure to
      gravity in human.

PMID- 15464290
TI  - R-type voltage-gated Ca(2+) channel interacts with synaptic proteins and recruits
      synaptotagmin to the plasma membrane of Xenopus oocytes.
AB  - It is well established that syntaxin 1A, synaptosomal-associated protein of 25
      kDa (SNAP-25) and synaptotagmin either alone or in combination, modulate the
      kinetic properties of voltage-gated Ca(2+) channels Ca(v)1.2 (Lc-channel)
      Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type). The interaction interface was found to
      reside at the cytosolic II-III domain of the alpha1 subunit of the channels. In
      this study, we demonstrated a functional coupling of human neuronal Ca(v)2.3 (R
      type channel) with syntaxin 1A, SNAP-25 and synaptotagmin in BAPTA injected
      Xenopus oocytes. The kinetic properties of Ca(v)2.3 assembled with syntaxin 1A,
      SNAP-25 or synaptotagmin individually differed from Ca(v)2.3 associated with
      binary complexes syntaxin 1A/SNAP-25, syntaxin 1A/synaptotagmin or SNAP
      25/synaptotagmin. Co-expression of Ca(v)2.3 with syntaxin 1A, SNAP-25 and
      synaptotagmin together, produced a channel with distinctive kinetic properties
      analogous to excitosome multiprotein complex generated by Ca(v)1.2 and Ca(v)2.2.
      Exchanging the current-carrying ions altered the kinetics of channel/synaptic
      proteins interaction, indicating a tight crosstalk formed between the permeation
      pathway of Ca(v)2.3 and the fusion apparatus during membrane depolarization. This
      putative coupling could predict how the release site might be organized to allow
      a rapid communication between the channel and the release machinery. In vivo
      confocal imaging of oocytes revealed GFP-synaptotagmin at the plasma membrane
      when the channel was present, as opposed to random distribution in its absence,
      consistent with Ca(2+)-independent molecular link of synaptotagmin and the
      channel. Synaptotagmin was detected at the membrane also in oocytes co-expressing
      the soluble N-ethylmaleimide-sensitive factor attachment protein receptors
      (SNAREs). Both imaging studies and protein-protein interactions in Xenopus
      oocytes show that channel linkage to synaptotagmin precedes Ca(2+) influx.
      Altogether, the R-type channel appears to associate with synaptic proteins to
      generate a multiprotein excitosome complex prior to Ca(2+)-entry. We propose that
      the distinct kinetics of the Ca(2+)-channel acquired by the close association
      with the vesicle and the t-SNAREs within the excitosome complex may be essential
      for depolarization evoked transmitter release.

PMID- 15464291
TI  - An immunocytochemical mapping of methionine-enkephalin-Arg(6)-Gly(7)-Leu(8) in
      the human brainstem.
AB  - Using an indirect immunoperoxidase technique, we studied the distribution of
      immunoreactive fibers and cell bodies containing methionine-enkephalin-Arg(6)
      Gly(7)-Leu(8) in the adult human brainstem. Immunoreactive cell bodies were found
      in the reticular formation of the medulla oblongata (in which we observed the
      highest density of immunoreactive cell bodies) and the pons, the solitary
      nucleus, the hypoglossal nucleus, the medial and spinal vestibular nuclei, the
      lateral cuneate nucleus, the nucleus prepositus, the central gray of the pons and
      mesencephalon, the central and pericentral nuclei of the inferior colliculus, the
      superior colliculus, ventral to the superior olive and in the midline region of
      the pons and mesencephalon. The highest density of immunoreactive fibers
      containing methionine-enkephalin-Arg(6)-Gly(7)-Leu(8) was found in the spinal
      trigeminal nucleus, the central gray and the reticular formation of the medulla
      oblongata, pons and mesencephalon, the solitary nucleus, the spinal vestibular
      nucleus, the dorsal accessory olivary nucleus, the raphe obscurus, the substantia
      nigra and in the interpeduncular nucleus. The widespread distribution of
      immunoreactive structures containing methionine-enkephalin-Arg(6)-Gly(7)-Leu(8)
      in the human brainstem indicates that this neuropeptide might be involved in
      several physiological mechanisms, acting as a neurotransmitter and/or
      neuromodulator.

PMID- 15464292
TI  - Spatial distribution of functional superficial-deep connections in the adult
      ferret superior colliculus.
AB  - Numerous studies have identified connections between the superficial visual and
      deeper multisensory layers of the superior colliculus (SC), but the functional
      distribution of the superficial-deep projection has not been mapped. This
      question was assessed in the present study using extracellular
      electrophysiological stimulation and recording techniques. In vitro slices from
      adult ferrets were used to functionally map the rostro-caudal, medio-lateral, and
      dorso-ventral distribution of these superficial-deep connections. For each
      coronal (n=6) or parasagittal (n=10) slice, single and multi-unit responses to
      electrical stimulation of a point in the superficial layers were systematically
      recorded at different locations along a grid (approximately 300 microm intervals)
      across the slice. Recording sites with similar activation thresholds were grouped
      on the histological reconstruction of each slice to plot the functional access of
      superficial stimulation site to the deeper layers. Low intensity stimulation
      (defined as a current threshold < or =75 microA) activated areas of the subjacent
      intermediate layers in most cases (75%; 12/16). Higher intensity stimuli (> 75
      600 microA) accessed larger areas which, in 50% of the slices, extended into the
      deepest layers of the SC. However, regardless of the rostro-caudal or medio
      lateral position of the superficial layer stimulation site, the proportion of the
      deeper layers activated remained remarkably constant, although the volume of
      activated deep layer tissue was shifted in each case toward the central regions
      of the SC. This last observation argues against the precise alignment of the
      superficial and deep layer visual maps, suggesting instead that the arrangement
      of the superficial layer projection may more closely relate to the organization
      of deep layer auditory and/or somatosensory representations.

PMID- 15464293
TI  - Tonotopic and heterotopic projection systems in physiologically defined auditory
      cortex.
AB  - Combined physiological and connectional studies show significant non-topographic
      extrinsic projections to frequency-specific domains in the cat auditory cortex.
      These frequency-mismatched loci in the thalamus, ipsilateral cortex, and
      commissural system complement the predicted topographic and tonotopic
      projections. Two tonotopic areas, the primary auditory cortex (AI) and the
      anterior auditory field (AAF), were electrophysiologically characterized by their
      frequency organization. Next, either cholera toxin beta subunit or cholera toxin
      beta subunit gold conjugate was injected into frequency-matched locations in each
      area to reveal the projection pattern from the thalamus and cortex. Most
      retrograde labeling was found at tonotopically appropriate locations within a 1
      mm-wide strip in the thalamus and a 2-3 mm-wide expanse of cortex (approximately
      85%). However, approximately 13-30% of the neurons originated from frequency
      mismatched locations far from their predicted positions in thalamic nuclei and
      cortical areas, respectively. We propose that these heterotopic projections
      satisfy at least three criteria that may be necessary to support the magnitude
      and character of plastic changes in physiological studies. First, they are found
      in the thalamus, ipsilateral and commissural cortex; since this reorganization
      could arise from any of these routes and may involve each, such projections ought
      to occur in them. Second, they originate from nuclei and areas with or without
      tonotopy; it is likely that plasticity is not exclusively shaped by spectral
      influences and not limited to cochleotopic regions. Finally, the projections are
      appropriate in magnitude and sign to plausibly support such rearrangements; given
      the rapidity of some aspects of plastic changes, they should be mediated by
      substantial existing connections. Alternative roles for these heterotopic
      projections are also considered.

PMID- 15464294
TI  - The contribution of autophosphorylated alpha-calcium-calmodulin kinase II to
      injury-induced persistent pain.
AB  - Increases in neuronal activity in response to tissue or nerve injury can lead to
      prolonged functional changes in the spinal cord resulting in an
      enhancement/sensitization of nociceptive processing. To assess the contribution
      of alpha-calcium-calmodulin kinase II (alpha-CaMKII) to injury-induced
      inflammation and pain, we evaluated nociceptive responses in mice that carry a
      point mutation in the alpha-CaMKII gene at position 286 (threonine to alanine).
      The mutated protein is unable to autophosphorylate and thus cannot function
      independently of calcium and calmodulin. Responses to acute noxious stimuli did
      not differ between alpha-CaMKII T286A mutant and wild type mice. However, the
      ongoing pain produced by formalin injury was significantly reduced in the mutant
      mice, as was formalin-evoked spinal Fos-immunoreactivity. In contrast, the
      decreased mechanical and thermal thresholds associated with nerve injury,
      Complete Freund's Adjuvant-induced inflammation or formalin-evoked tissue injury
      were manifest equally in wild-type and mutant mice. Double-labeling
      immunofluorescence studies revealed that in the mouse alpha-CaMKII is expressed
      in the superficial dorsal horn as well as in a population of small diameter
      primary afferent neurons. In summary, our results suggest that alpha-CaMKII,
      perhaps secondary to an N-methyl-D-aspartate-mediated calcium increase in
      postsynaptic dorsal horn nociresponsive neurons, is a critical contributor to the
      spontaneous/ongoing component of tissue-injury evoked persistent pain.

PMID- 15464295
TI  - Differential expression of purinergic receptor subtypes in the outer hair cells
      of the guinea pig.
AB  - ATP acts as a neuro-modulator through purinoceptors in many different tissues.
      Many subtypes of these receptors have been identified in the inner ear, but so
      far only two types have been shown to be present in the membrane of the isolated
      outer hair cells (OHCs). The aim of this study was to detect and visualize the
      existence and distribution of purinoceptor subtypes as well as to study the
      [Ca(2+)](i) response of these cells in response to stimulation with ATP. Four P2X
      and three P2Y receptor subtypes were identified with different expression pattern
      in the membrane of guinea pig outer hair cells. Whereas intense labeling was
      observed for P2X1, P2X2, P2X4, P2Y1, P2Y2, and P2Y4, the labeling for the subtype
      P2X7 was weak. There was a marked difference in the distribution of the receptors
      along the surface of the cells with a homogenous distribution in cases of P2X1,
      P2X4, and P2Y1. In contrast, P2X2 and P2Y2 receptor density was high mainly at
      the apical, while P2X7 and P2Y4 at the basal pole of the cells. Similarly a
      heterogeneity was observed in the ATP-induced transient elevation in [Ca(2+)](i),
      which had either fast kinetics without desensitization or slow rise with
      desensitization.

PMID- 15464296
TI  - RNA expression induced by cisplatin in an organ of Corti-derived immortalized
      cell line.
AB  - Cisplatin [cis-diamminedichloroplatinum(II)] (CDDP) is an organic compound that
      is widely used for the treatment of a large number of tumors. Its clinical use is
      limited by the presence of some undesired side effects, like as oto- and nephro
      toxicity, whose mechanisms of action are not understood. One of the possible CDDP
      toxicity mechanism seems to involve the generation of reactive oxygen species
      (ROS), that can impair morphology and function of hair cells (HC) in the organ of
      Corti. To test this hypothesis we evaluated the effect of CDDP treatment on RNA
      steady-state levels of 15,000 genes by microarray analysis, using, as a
      experimental model, the OC-k3 cell line, obtained from the organ of Corti of
      transgenic mice and constitutively expressing the large SV40 T antigen. We have
      found overexpression of several genes related to arachidonate mobilization
      including phospholipase A2, group IV and V, phospholipase A2 activating protein
      and lysophospholipase I and III, as well as lipoxygenation like arachidonate 12
      lipoxygenase and arachidonate 5-lipoxygenase activating protein. In addition, we
      found significant transcription of genes regulating cell respiration, including
      cyt c oxidase, as well as genes involved in xenobiotic detoxification and lipid
      peroxidation such as cyt P450, and other oxidases including spermine oxidase and
      monoamine oxidase. As a whole, overexpression of the group of different genes
      seems to indicate that an oxidative burst could take place during cisplatin
      administration. We therefore searched for evidences of superoxide anion and
      hydrogen peroxide by means of electron paramagnetic resonance (EPR) spectroscopy
      and flow cytometry, but failed to detect them. On the other hand, we found an
      increase of malondialdehyde (MDA) synthesis and protein carbonylation products,
      indicating the occurence of lipid peroxidative degradation. When we tested the
      effectiveness of butylated hydroxytoluene (BHT), dithiothreitol (DTT) and N
      acetylcysteine (N-Ac) as cytoprotectants, all of them reduced protein
      carbonylation to control levels and significantly protected OC-k3 from CDDP
      induced cell death, with an higher protection when using the lipophylic
      antioxidant BHT. The same antioxidants prevented also the onset of protein
      carbonylation, which extent was decreased to basal levels. These data indicate
      that CDDP is able to stimulate gene expression up to 12 h after the beginning of
      the treatment. This increase in gene transcription involves a large number of
      genes potentially able to increase the level of cell ROS. Consistently, cells
      survival is improved by cotreatment with antioxidants, in particular lipophilics.

PMID- 15464297
TI  - Trophic effects of insulin-like growth factor-I (IGF-I) in the inner ear.
AB  - Insulin-like growth factors (IGFs) have a pivotal role during nervous system
      development and in its functional maintenance. IGF-I and its high affinity
      receptor (IGF1R) are expressed in the developing inner ear and in the postnatal
      cochlear and vestibular ganglia. We recently showed that trophic support by IGF-I
      is essential for the early neurogenesis of the chick cochleovestibular ganglion
      (CVG). In the chicken embryo otic vesicle, IGF-I regulates developmental death
      dynamics by regulating the activity and/or levels of key intracellular molecules,
      including lipid and protein kinases such as ceramide kinase, Akt and Jun N
      terminal kinase (JNK). Mice lacking IGF-I lose many auditory neurons and present
      increased auditory thresholds at early postnatal ages. Neuronal loss associated
      to IGF-I deficiency is caused by apoptosis of the auditory neurons, which
      presented abnormally increased levels of activated caspase-3. It is worth noting
      that in man, homozygous deletion of the IGF-1 gene causes sensory-neural
      deafness. IGF-I is thus necessary for normal development and maintenance of the
      inner ear. The trophic actions of IGF-I in the inner ear suggest that this factor
      may have therapeutic potential for the treatment of hearing loss.

PMID- 15464298
TI  - The usefulness of computerized dynamic posturography for the study of equilibrium
      in patients with Meniere's disease: correlation with clinical and audiologic
      data.
AB  - The use of computerized dynamic posturogaphy (CDP) in the evaluation of patients
      with balance alterations not only allows quantification of the subject's capacity
      to maintain a stable centre of gravity, but also analysis of the degree to which
      the subject is able to use different types of sensory information. The present
      study investigated the possible use of CDP for clinical staging of vestibular
      diseases, specifically Meniere's disease (MD). We applied CDP sensory
      organization tests to 75 patients with definitive MD (AAO-HNS 1995 criteria). A
      total of 98 CDP sessions were included in the analysis, which focused on four CDP
      parameters specifically related to vestibular function (condition-5 score,
      condition-6 score, overall balance score, and VEST, a measure of the relative
      importance of vestibular information for maintenance of balance). We found a
      statistically significant relationship between audiometric hearing threshold and
      CDP scores, especially in patients with audiometrically advanced disease. In
      addition, CDP scores showed statistically significant variation with time elapsed
      since the last typical vertigo attack, suggesting that patients can be usefully
      grouped into three MD activity-level categories: recent post-attack (less than 1
      week since last vertigo attack), late post-attack (1 week - 60 days since last
      attack), and inactive MD (more than 60 days since last attack). On the basis of
      these results, we propose expected ranges for each of the four CDP parameters in
      each of the three MD activity-level categories, allowing staging in terms of
      balance and posture. This staging system complements existing staging systems
      (based on audiometric criteria, and on subjective assessment of the severity of
      vertigo attacks and their implications for quality of life).

PMID- 15464299
TI  - Changes of 2-deoxyglucose uptake in the rat auditory pathway after bilateral
      ablation of the cochlea.
AB  - It has been reported that the area of decreased glucose metabolism in the FDG-PET
      of prelingually deaf children correlates significantly with speech performance
      after cochlear implantation. In this study, we undertook to confirm changes of
      glucose metabolism in the cerebral cortex using an animal model with age-matching
      groups to completely exclude the influence of age differences between the deaf
      and normal-hearing groups. The cochlea was ablated bilaterally at a postnatal 10
      14 days in the deaf groups; 3-4 deaf and normal rats were included at each time
      point at 1, 2, 4 and 8 weeks and 7 months after ablation. After injecting 2
      deoxyglucose intraperitoneally, digitalized autoradiographic images were
      obtained, and analyzed by using two different methods; 3-dimensional voxel-wise
      statistical analysis and conventional 2-dimensional densitometry. The
      hypometabolic area analyzed using 3-dimensional analysis and the differences of
      optical density between normal and deaf as determined by densitometry were widest
      and most prominent between 4 and 8 weeks after ablation. Differences were not
      significant before 2 weeks or after 7 months after ablation. This result shows
      that the hypometabolic area becomes prominent after a critical period and it
      decreases as the duration of deafness increases. We believe that cross-modal
      plasticity may be the mechanism of changes in glucose metabolism and that this
      result reinforced the usefulness of evaluating hypometabolic area using FDG-PET
      in deaf children.

PMID- 15464300
TI  - Localization of the mitochondrial uncoupling protein family in the rat inner ear.
AB  - Uncoupling proteins (UCPs) are a proton transporter family located in the
      mitochondrial inner membrane. The molecular expression and activity of UCPs in
      brown adipose tissue and skeletal muscle are regulated by factors as diverse as
      chronic overeating and cold exposure, suggesting roles in energy expenditure and
      heat production. Although UCP2, UCP4 and brain mitochondrial carrier protein-1
      (BMCP-1, i.e. UCP5) mRNAs are expressed in the central nervous system, their
      central function is unknown. This study presents the first evidence on
      localization and quantitative expression of UCPs in the rat inner ear by real
      time PCR and immunohistochemistry. Real-time PCR studies revealed that UCP2 mRNA
      was expressed in the vestibular and spiral ganglia more abundantly than any other
      UCP. Neocortex, by contrast, contained UCP2 and UCP4 equally. Notably, UCP3 and
      UCP4 mRNAs were expressed in inner ear ganglia, but brain UCP3 mRNA expression
      level was undetectable by simple PCR. Immunohistochemical studies confirmed that
      both UCP2- and UCP3-like immunoreactivities were detected in vestibular and
      spiral ganglion cells and co-localized with a mitochondrial marker,
      MitoFluorGreen. According to previous reports, UCP2 and UCP3 are thermogenic in
      yeast and brain UCP2 has been suggested to modulate pre- and post-synaptic events
      by axonal thermogenesis. It has also been reported recently that UCP2 and UCP3
      responses to superoxide application may be an antioxidant protective mechanism.
      Therefore, it is suggested that mitochondrial UCPs (UCP2, UCP3, UCP4) may play
      both a protective role against oxidative damage and a thermal signaling role in
      the eighth nerve.

PMID- 15464301
TI  - Pulse rate discrimination with deeply inserted electrode arrays.
AB  - Pulse rate difference limen (PRDL) and amplitude modulation difference limen
      (AMDL) were assessed as a function of base rate and cochlear electrode location
      in seven (three for AMDL) subjects implanted with the MED-EL COMBI 40+ implant.
      The MED-EL COMBI 40+ electrode array allows deep insertion of the electrode up to
      the apex of the cochlea to minimize the rate/place mismatch for pulse rates below
      500 pps. A three interval, two alternative forced-choice procedure with feedback
      was used to measure the difference limen. The base rate was in the range between
      200 and 800 pps. The carrier rate for the AMDL measurement was 5081 pps. The PRDL
      increased with increasing base pulse rate. At 200 pps the average PRDL measured
      at the apical electrode amounted to 48.7 pps, at 400 pps the average PRDL reached
      206.6 pps. No significant difference between PRDL obtained from apical or basal
      electrodes could be observed. AMDL was higher than PRDL at all tested base rates.
      The ability to discriminate rate changes is limited to base rates up to about 283
      pps. The results indicate that rate changes smaller than a major third do not
      elicit distinguishable auditory perceptions in electrical hearing. The absence of
      a difference between apical and basal electrode locations indicates that a
      reduction of the rate/place mismatch does not improve discrimination performance.

PMID- 15464302
TI  - Direct inner ear infusion of dexamethasone attenuates noise-induced trauma in
      guinea pig.
AB  - The protective effect of dexamethasone (DEX) against noise-induced trauma, as
      reflected in hair cell destruction and elevation in auditory brainstem response
      (ABR) sensitivity, was assessed in guinea pigs. The animals were administered DEX
      (1, 10, 100, and 1000 ng/ml) or artificial perilymph (AP) via a mini-osmotic pump
      directly into scala tympani and, on the fourth day after pump implantation,
      exposed to 120 dB SPL octave band noise, centered at 4 kHz, for 24 h. Animals
      receiving DEX demonstrated a dose-dependent reduction in noise-induced outer hair
      cell loss (significant at 1, 10 and 100 ng/ml DEX animals compared to AP control
      animals) and a similar attenuation of the noise-induced ABR threshold shifts,
      observed 7 days following exposure (significant at 100 ng/ml DEX animals compared
      to AP control animals). These physiological and morphological results indicate
      that direct infusion of DEX into the perilymphatic space has protective effects
      against noise-induced trauma in the guinea pig cochlea.

PMID- 15464303
TI  - Quantitative analysis of apoptotic and necrotic outer hair cells after exposure
      to different levels of continuous noise.
AB  - We have reported that by 2 days after noise exposure the size of cochlear lesion
      was expanding by outer hair cells (OHCs) dying either by apoptosis or necrosis.
      The current study was designed to compare the prevalence of the two cell death
      pathways as a function of time after exposure to noises of different levels.
      Chinchillas were exposed to a narrow band noise at either 104 or 108 dB SPL for 1
      h. At three time points (1, 4 and 30 days) after the noise exposure, the numbers
      of missing, apoptotic and necrotic OHCs in the cochleas were identified and
      documented with a combination of TUNEL, caspase-3 and propidium iodide labeling.
      The subjects exposed to the 108-dB noise showed significantly more apoptotic OHCs
      than necrotic OHCs in the cochleas examined at days 1 and 4 after the noise
      exposure. By day 30, apoptotic and necrotic pathologies continued, although in
      small quantity, with no significant difference in quantity between two types of
      cell death. The subjects exposed to the 104-dB noise showed a significant
      difference in the numbers of apoptotic and necrotic OHCs at day 1 after the noise
      exposure, whereas the difference became statistically insignificant at day 4 and
      day 30 after the noise exposure. The results of the study indicate that the early
      expansion of cochlear lesion is attributed primarily to apoptosis, whereas the
      later stage of lesion expansion is likely the result of an equal contribution
      from apoptosis and necrosis.

PMID- 15464304
TI  - N1m recovery from decline after exposure to noise with strong spectral contrasts.
AB  - Comb-filtered noise (CFN, derived from white noise by suppressing regularly
      spaced frequency regions) was presented for 3 s followed by two types of test
      stimuli. One test stimulus (SB) was comprised of spectra centered in the stop
      band regions of the CFN and the other test stimulus (PB) of spectra centered in
      the band pass regions of the CFN. Magnetoencephalographically recorded N1m
      responses evoked by SB stimuli were decreased relative to the N1m response evoked
      by PB stimuli. This effect was maximal when the interval between the CFN and test
      stimuli was short (0.5 s) but was detected at intervals up to 2 s. The results
      suggest lateral inhibition in the auditory cortex and point to a decay of
      inhibition lasting on the order of seconds.

PMID- 15464305
TI  - Prevalence of the GJB2 mutations and the del(GJB6-D13S1830) mutation in Brazilian
      patients with deafness.
AB  - Mutations in the GJB2 gene are the most common cause of sensorineural non
      syndromic deafness in different populations. One specific mutation, 35delG, has
      accounted for the majority of the mutations detected in the GJB2 gene in many
      countries. The aim of this study was to determine the prevalence of GJB2
      mutations and the del(GJB6-D13S1830) mutation in non-syndromic deaf Brazilians.
      The 33 unrelated probands were examined by clinical evaluation to exclude
      syndromic forms of deafness. Mutation analysis in the GJB2 gene and the testing
      for the del(GJB6-D13S1830) were performed in both the patients and their family
      members. The 35delG mutation was found in nine of the probands or in 14 of the
      mutated alleles. The V37I mutation and the del(GJB6-D13S1830) mutation were also
      found in two patients, both are compound heterozygote with 35delG mutation. These
      findings strengthen the importance of genetic diagnosis, providing early
      treatment, and genetic counseling of deaf patients.

PMID- 15464306
TI  - Temporary DPOAE level shifts, ABR threshold shifts and histopathological damage
      following below-critical-level noise exposures.
AB  - DPOAE temporary level shift (TLS) at 2f(1)-f(2) and f(2)-f(1), ABR temporary
      threshold shift (TTS), and detailed histopathological findings were compared in
      three groups of chinchillas that were exposed for 24 h to an octave band of noise
      (OBN) centered at 4 kHz with a sound pressure level (SPL) of 80, 86 or 92 dB
      (n=3,4,6). DPOAE levels at 39 frequencies from f(1)=0.3 to 16 kHz
      (f(2)/f(1)=1.23; L(2) and L(1)=55, 65 and 75 dB, equal and differing by 10 dB)
      and ABR thresholds at 13 frequencies from 0.5 to 20 kHz were collected pre- and
      immediately post-exposure. The functional data were converted to pre- minus post
      exposure shift and overlaid upon the cytocochleogram of cochlear damage using the
      frequency-place map for the chinchilla. The magnitude and frequency place of
      components in the 2f(1)-f(2) TLS patterns were determined and group averages for
      each OBN SPL and L(1), L(2) combination were calculated. The f(2)-f(1) TLS was
      also examined in ears with focal lesions equal to or greater than 0.4 mm. The
      2f(1)-f(2) TLS (plotted at f(1)) and TTS aligned with the extent and location of
      damaged supporting cells. The TLS patterns over frequency had two features which
      were unexpected: (1) a peak at about a half octave above the center of the OBN
      with a valley just above and below it and (2) a peak (often showing enhancement)
      at the apical boundary of the supporting-cell damage. The magnitudes of the TLS
      and TTS generally increased with increasing SPL of the exposure. The peaks of the
      TLS and TTS, as well as the peaks and valleys of the TLS pattern moved apically
      as the SPL of the OBN was increased. However, there was little consistency in the
      pattern relations with differing L(1), L(2) combinations. In addition, neither
      the 2f(1)-f(2) nor f(2)-f(1) TLS for any L(1), L(2) combination reliably detected
      focal lesions (100% OHC loss) from 0.4 to 1.2 mm in size. Often, the TLS went in
      the opposite direction from what would be expected at focal lesions. Recovery
      from TLS and TTS was also examined in seven animals. Both TLS and TTS recovered
      partially or completely, the magnitude depending upon exposure SPL.

PMID- 15464307
TI  - Auditory evoked magnetic fields in relation to interaural cross-correlation of
      band-pass noise.
AB  - Auditory evoked magnetic fields of the human brain were analyzed in relation to
      the magnitude of the inter-aural cross-correlation (IACC). IACC of the stimuli
      was controlled by mixing diotic bandpass and dichotic independent bandpass noise
      in appropriate ratios. The auditory stimuli were binaurally delivered through
      plastic tubes and earpieces inserted into ear canals of the nine volunteers with
      normal hearing who took part in this study. All source signals had the same sound
      pressure level. Auditory evoked fields (AEFs) were recorded using a
      neuromagnetometer in a magnetically shielded room. Combinations of a reference
      stimulus (IACC=1.0) and test stimuli (IACC=0.2, 0.6, 0.85) were presented
      alternately at a constant interstimulus interval of 0.5 s and MEGs recorded. The
      results showed that the N1m latencies were not affected by IACC; however, the
      peak amplitude of N1m significantly decreased with increasing IACC.

PMID- 15464308
TI  - Screening for monogenetic del(GJB6-D13S1830) and digenic del(GJB6-D13S1830)/GJB2
      patterns of inheritance in deaf individuals from Eastern Austria.
AB  - Genetically caused congenital deafness is a common trait affecting 1 in 2000
      newborn children and is predominantly inherited in an autosomal recessive
      fashion. Genes such as the gap junction protein beta 2 (GJB2) encoding for
      Connexin (Cx26) and GJB6 (Cx30) are known to cause sensorineural deafness.
      Autosomal recessive deafness has been linked both to the monogenetic occurrence
      of mutated GJB2 or the GJB6 deletion del(GJB6-D13S1830) and digenic GJB2/del(GJB6
      D13S1830) inheritance. Monogenetic GJB2 alterations are responsible for 25.5% of
      deafness in the eastern Austrian population. An additional 9.8% are heterozygous
      carriers of a single GJB2 mutation which is not responsible for deafness alone.
      Del(GJB6-D13S1830) and GJB2/del(GJB6-D13S1830) mutations have been shown to be
      the second most frequent cause of deafness in different populations. To address
      the question of the relevance of mutations in GJB6 either as a monogenetic or a
      digenic GJB2/del(GJB6-D13S1830) cause of deafness in this population, 76
      unrelated individuals (33 families and 43 sporadic cases) were screened using PCR
      strategies. Similar to studies in other hard of hearing populations with similar
      or lower carrier frequencies of single GJB2 mutations, the presence of del(GJB6
      D13S1830) was not detected in any individual within the patient group. Data
      therefore exclude a digenetic association of del(GJB6-D13S1830) with heterozygous
      GJB2 mutations as a cause of deafness in a representative sample of the
      population from Eastern Austria.

PMID- 15464309
TI  - Stimulus dependence of spectro-temporal receptive fields in cat primary auditory
      cortex.
AB  - The frequency-tuning curve is a static representation of the neuron's sensitivity
      to stimulus frequency. The temporal aspects of the frequency sensitivity can be
      captured in the spectro-temporal receptive field (STRF), often presented as the
      average spectrogram of the stimulus preceding a spike but also as the average
      frequency-dependent post-stimulus time histogram (PSTH). The temporal envelope of
      the stimulus produces considerable smoothing, and as a consequence the PSTH
      representation is finer-grained than the spectrogram representation. Here we
      compare STRFs for 1/s and 20/s single-frequency stimuli with 120/s steady-state
      multi-frequency stimuli for 87 recording sites in primary auditory cortex of
      cats. For the 672 estimated STRFs, which for multi-frequency stimuli were mostly
      obtained at 55 dB SPL, we found lateral inhibition in 17% of the cases, in 32%
      post-activation suppression, and in 51% only excitation. In 35% of the recordings
      the excitatory frequency-tuning curves were very similar for single and multi
      frequency stimuli, in the remaining 65% the common finding was the emergence of
      an intensity independent bandwidth for the multi-frequency stimuli. Comparison of
      the 20/s and 120/s stimuli showed that the resulting increase in inhibition was
      strongest in the center of the STRF.

PMID- 15464310
TI  - The renal patient with coronary artery disease: current concepts and dilemmas.
AB  - The patient with chronic kidney disease and coronary artery disease (CAD)
      presents special challenges. This report reviews the scope of the challenge, the
      hostile internal milieu predisposing to CAD and cardiac events, management
      issues, unresolved dilemmas, and the need for randomized trials to allow for
      evidence-based treatment.

PMID- 15464311
TI  - The evolving challenge of chronic heart failure management: a call for a new
      curriculum for training heart failure specialists.
AB  - Chronic heart failure (HF) is a growing epidemic, and therapy options are
      becoming more complex. Specifically, device management of HF represents a new
      "class" of therapy that can reduce mortality and alleviate morbidity of the
      disease syndrome. Heart failure training programs seldom provide structured
      opportunities for trainees to gain competence in device implantation and
      management. This curriculum outlines a new approach to training interventional HF
      cardiologists and internal medicine HF specialists to meet the growing demands
      for specially trained health care providers.

PMID- 15464312
TI  - Does it make sense to train plumbers as electricians?
AB  - There is an expanded need for implantable cardioverter-defibrillators and cardiac
      resynchronization pacemakers as part of the treatment of patients with left
      ventricular dysfunction. A large number of such patients present to heart failure
      (HF) specialists for recommendations related to their care. In this paper, a
      pathway is presented that would combine training in HF/transplantation and
      cardiac implantable electrical devices.

PMID- 15464313
TI  - Heart failure training: a call for an integrative, patient-focused approach to an
      emerging cardiology subspecialty.
AB  - The coming years will see continued growth in the epidemic of heart failure (HF)
      and increasingly complex pharmacologic, interventional, and device-based
      therapies, effective in reducing HF morbidity and mortality. Highly trained
      clinician-specialists are needed to assist in optimally evaluating and managing
      patients with HF. The patient is the central element defining the skills needed
      within this cardiology subspecialty. Primary care education, disease management
      strategies, and effective communication among HF specialists and other clinicians
      are key systemic elements needed to deliver the increasingly complex array of
      treatments to the expanding population of patients with HF.

PMID- 15464314
TI  - Actinomycin-eluting stent for coronary revascularization: a randomized
      feasibility and safety study: the ACTION trial.
AB  - OBJECTIVES: We sought to demonstrate the safety and performance of the
      actinomycin D-coated Multilink-Tetra stent(Guidant Corp., Santa Clara,
      California) in the treatment of patients with single de novo native coronary
      lesions. BACKGROUND: Drug-eluting stents (DES) releasing sirolimus or paclitaxel
      dramatically reduce restenosis. The anti-proliferative drug, actinomycin D, which
      is highly effective in reducing neointimal proliferation in preclinical studies,
      was selected for clinical evaluation. METHODS: The multi-center, single-blind,
      three-arm ACTinomycin-eluting stent Improves Outcomes by reducing Neointimal
      hyperplasia (ACTION) trial randomized 360 patients to receive a DES (2.5 or 10
      microg/cm(2) of actinomycin D) or metallic stent (MS). The primary end points
      were major adverse cardiac events (MACE) at 30 days, diameter stenosis by
      angiography, tissue effects, and neointimal volume by intravascular ultrasound
      (IVUS) at six months. When early monitoring revealed an increased rate of repeat
      revascularization, the protocol was amended to allow for additional follow-up for
      DES patients. Angiographic control of MS patients was no longer mandatory.
      RESULTS: The biased selection of DES patients undergoing IVUS follow-up
      invalidated the interpretation of the IVUS findings. The in-stent late lumen loss
      and that at the proximal and distal edges were higher in both DES groups than in
      the MS group and resulted in higher six-month and one-year MACE (34.8% and 43.1%
      vs. 13.5%), driven exclusively by target vessel revascularization without excess
      death or myocardial infarction. CONCLUSIONS: The results of the ACTION trial
      indicate that all anti-proliferative drugs will not uniformly show a drug class
      effect in the prevention of restenosis.

PMID- 15464315
TI  - High-dose 7-hexanoyltaxol-eluting stent with polymer sleeves for coronary
      revascularization: one-year results from the SCORE randomized trial.
AB  - OBJECTIVES: The Study to COmpare REstenosis Rate between QueST and QuaDDS-QP2
      (SCORE) trial was a multicenter, randomized, open-label trial comparing the
      safety and performance of 13- and 17-mm QuaDDS stents (n = 126) (Quanam Medical
      Corp., Santa Clara, California/Boston Scientific Corp., Natick, Massachusetts)
      versus uncoated control stents (n = 140) in focal, de novo coronary lesions.
      BACKGROUND: The pioneering drug-delivery QuaDDS stent used four to six acrylate
      polymer sleeves, each loaded with 800 microg of the paclitaxel derivative 7
      hexanoyltaxol. METHODS: Clinical end points were assessed at 1, 6, and 12 months
      post procedure. Quantitative coronary angiography and intravascular ultrasound
      were performed post procedure and at six-month follow-up. RESULTS: In the QuaDDS
      group, early stent thrombosis and myocardial infarction (MI) rates were
      significantly higher, leading to premature cessation of enrollment. For the
      QuaDDS group, the stent thrombosis rate increased from 3.2% to 10.3% between 1
      and 12 months, associated with increased non-Q-wave MI and death rates. The
      angiographic restenosis rate at six months was reduced from 32.7% (control) to
      7.4% (p < 0.0001). However, the primary end point was not met with six-month
      target vessel revascularization (TVR) rate as well as the composite major adverse
      cardiac event rates (cardiac death, MI, and TVR) comparable between groups.
      CONCLUSIONS: Despite angiographic indications of potential anti-restenotic
      benefit, increased rates of stent thrombosis, MI, and cardiac death associated
      with the QuaDDS stent show an unacceptable safety profile.

PMID- 15464316
TI  - Preclinical restenosis models and drug-eluting stents: still important, still
      much to learn.
AB  - Percutaneous coronary intervention continues to revolutionize the treatment of
      coronary atherosclerosis. Restenosis remains a significant problem but may at
      last be yielding to technologic advances. The examination of neointimal
      hyperplasia in injured animal artery models has helped in our understanding of
      angioplasty and stenting mechanisms, and as drug-eluting stent (DES) technologies
      have arrived, they too have been advanced through the study of animal models.
      These models are useful for predicting adverse clinical outcomes in patients with
      DESs because suboptimal animal model studies typically lead to problematic human
      trials. Similarly, stent thrombosis in animal models suggests stent
      thrombogenicity in human patients. Equivocal animal model results at six or nine
      months occasionally have been mirrored by excellent clinical outcomes in
      patients. The causes of such disparities are unclear but may result from
      differing methods, including less injury severity than originally described in
      the models. Ongoing research into animal models will reconcile apparent
      differences with clinical trials and advance our understanding of how to apply
      animal models to clinical stenting in the era of DESs.

PMID- 15464317
TI  - Oral rapamycin to inhibit restenosis after stenting of de novo coronary lesions:
      the Oral Rapamune to Inhibit Restenosis (ORBIT) study.
AB  - OBJECTIVES: The aim of this study was to establish safety and feasibility of oral
      Rapamycin at two doses-2 mg and 5 mg-in achieving low rates of repeat target
      lesion revascularization (TLR) in de novo native coronary artery lesions.
      BACKGROUND: Drug-eluting stents have shown the ability to limit restenosis. Oral
      Rapamycin is an alternative strategy that can target multiple coronary lesions
      suitable for treatment with any approved metal stent and at potentially lower
      cost. METHODS: The Oral Rapamune to Inhibit Restenosis (ORBIT) study is an open
      label study of 60 patients with de novo lesions treated with bare metal stents in
      up to two vessels. After a loading dose of 5 mg, patients received a daily dose
      of 2 mg (n = 30) and 5 mg (n = 30) for 30 days. Six-month angiographic,
      intravascular ultrasound (IVUS), and clinical follow-up were conducted. RESULTS:
      Baseline clinical and procedural characteristics were similar: 10% of patients in
      the 2-mg group and 30% in the 5-mg group did not complete the course; 43% in the
      2-mg group and 66% in the 5-mg group had side effects. At six-month follow-up,
      late loss (0.6 +/- 0.5 mm vs. 0.7 +/- 0.5 mm; p = NS), in-stent binary restenosis
      (7.1% vs. 6.9%; p = NS), in-stent percent volume obstruction by IVUS (29% vs.
      24%; p = NS), and clinically driven TLR (14.3% vs. 6.9%; p = NS) were similar in
      2-mg and 5-mg groups. CONCLUSIONS: Oral Rapamycin for the prevention of
      restenosis is safe, feasible, and associated with low rates of repeat
      revascularization. Although associated with certain side effects, it may be
      considered for patients undergoing multivessel stents if proven in larger
      randomized studies.

PMID- 15464318
TI  - A simple risk score for prediction of contrast-induced nephropathy after
      percutaneous coronary intervention: development and initial validation.
AB  - OBJECTIVES: We sought to develop a simple risk score of contrast-induced
      nephropathy (CIN) after percutaneous coronary intervention (PCI). BACKGROUND:
      Although several risk factors for CIN have been identified, the cumulative risk
      rendered by their combination is unknown. METHODS: A total of 8,357 patients were
      randomly assigned to a development and a validation dataset. The baseline
      clinical and procedural characteristics of the 5,571 patients in the development
      dataset were considered as candidate univariate predictors of CIN (increase
      >or=25% and/or >or=0.5 mg/dl in serum creatinine at 48 h after PCI vs. baseline).
      Multivariate logistic regression was then used to identify independent predictors
      of CIN with a p value <0.0001. Based on the odds ratio, eight identified
      variables (hypotension, intra-aortic balloon pump, congestive heart failure,
      chronic kidney disease, diabetes, age >75 years, anemia, and volume of contrast)
      were assigned a weighted integer; the sum of the integers was a total risk score
      for each patient. RESULTS: The overall occurrence of CIN in the development set
      was 13.1% (range 7.5% to 57.3% for a low [<or=5] and high [>or=16] risk score,
      respectively); the rate of CIN increased exponentially with increasing risk score
      (Cochran Armitage chi-square, p < 0.0001). In the 2,786 patients of the
      validation dataset, the model demonstrated good discriminative power (c statistic
      = 0.67); the increasing risk score was again strongly associated with CIN (range
      8.4% to 55.9% for a low and high risk score, respectively). CONCLUSIONS: The risk
      of CIN after PCI can be simply assessed using readily available information. This
      risk score can be used for both clinical and investigational purposes.

PMID- 15464319
TI  - Procedural success versus clinical risk status in determining discharge of
      patients after primary angioplasty for acute myocardial infarction.
AB  - OBJECTIVES: We evaluated whether patients' clinical status, angioplasty success,
      or both, should guide discharge after primary angioplasty (i.e., percutaneous
      coronary intervention [PCI]) for acute myocardial infarction (AMI). BACKGROUND:
      Current guidelines do not address a discharge strategy for AMI patients
      undergoing successful PCI. METHODS: Patients who underwent PCI in Primary
      Angioplasty in Myocardial Infarction (PAMI) studies (N = 3,188) were classified
      as "high clinical risk" if they had either age >70 years, Killip class >1, heart
      rate >100 beats/min, systolic blood pressure <100 mm Hg, anterior MI, or left
      bundle branch block, and as "low clinical risk" if none was present. Successful
      PCI patients were compared with those with unsuccessful PCI in both groups for 30
      day major adverse cardiac events (MACE). RESULTS: Percutaneous coronary
      intervention was successful in 668 (90%) of 745 low-risk clinical and 2,104 (86%)
      of 2,443 high-risk clinical patients. Regardless of clinical risk status,
      patients with successful PCI had lower 30-day MACE than those with unsuccessful
      PCI (low-risk group: 4.6% vs. 22%, p < 0.0001; high-risk group: 7% vs. 21%; p <
      0.0001). Moreover, successful PCI patients with either risk status had few MACE
      after day 4, whereas unsuccessful PCI patients had more MACE. The success of PCI
      was the strongest independent predictor of 30-day MACE (odds ratio [OR] 3.7, 95%
      confidence interval [CI] 2.8 to 5.0). A constellation of three or more high-risk
      clinical features also predicted higher 30-day MACE (OR 2.25, 95% CI 1.62 to
      3.12). CONCLUSIONS: The success of PCI is the prime determinant of clinical
      outcome after PCI for AMI. The majority of AMI patients with less than three high
      risk clinical features who undergo successful PCI may be discharged from the
      hospital by day 4. In contrast, patients with more than two high-risk clinical
      features or unsuccessful PCI may need longer observation.

PMID- 15464320
TI  - Cilostazol inhibits leukocyte integrin Mac-1, leading to a potential reduction in
      restenosis after coronary stent implantation.
AB  - OBJECTIVES: The aim of this study was to confirm clinically a hypothesis that
      cilostazol inhibits leukocyte Mac-1, leading to prevention of post-stent
      restenosis. BACKGROUND: The platelet phosphodiesterase III inhibitor called
      cilostazol also inhibits alpha-granule release of P-selectin in platelets. The P
      selectin-mediated platelet-leukocyte interaction promotes activation and
      upregulation of leukocyte Mac-1 after coronary stenting, which plays a key role
      on the mechanism of restenosis. Thus, cilostazol's potential inhibition of this
      process may lead to prevention of restenosis. METHODS: Using flow cytometric
      analysis of whole blood obtained from the coronary sinus, the expression of
      platelet membrane glycoproteins and neutrophil adhesion molecules was observed in
      70 consecutive patients undergoing coronary stenting. The patients were randomly
      assigned to either a cilostazol or ticlopidine group before stent placement.
      RESULTS: The restenosis rate was lower (15% vs. 31%, p < 0.05) in the cilostazol
      group (n = 34) than in the ticlopidine group (n = 32). A stent-induced increase
      in platelet P-selectin (CD62P) expression and an increase in neutrophil Mac-1
      (CD11b) expression were suppressed in the cilostazol group compared with the
      ticlopidine group. Angiographic late lumen loss was correlated with the relative
      changes in platelet P-selectin and neutrophil Mac-1 at 48 h after coronary
      stenting. CONCLUSIONS: Cilostazol may have effects on suppression of P-selectin
      mediated platelet activation, platelet-leukocyte interaction, and subsequent Mac
      1-mediated leukocyte activation, which might lead to a reduced restenosis rate
      after coronary stent implantation.

PMID- 15464321
TI  - Brachytherapy: potential therapy for refractory coronary spasm.
AB  - OBJECTIVES: We sought to demonstrate that brachytherapy reduces coronary spasm in
      refractory and highly symptomatic variant angina. BACKGROUND: In some patients
      with variant angina due to extensive vasoconstriction, intensive drug therapy
      fails to sufficiently relieve symptoms. METHODS: In 18 patients with frequent
      angina episodes despite triple anti-anginal therapy, coronary spasm was induced
      by intracoronary acetylcholine (ACh) infusion. Five patients had spasm in a
      second vessel. Intracoronary radiation (20 Gy) was applied to vasospastic
      segments using a beta-emitting ((32)P) wire source centered within a Galileo
      balloon. Parameters of vessel function before and after brachytherapy were
      investigated. RESULTS: Before brachytherapy, artery diameters decreased (p <
      0.0001) from 2.8 +/- 0.4 mm to 1.0 +/- 0.4 mm for the first vessels and from 3.1
      +/- 0.3 mm to 1.0 +/- 0.2 mm for the second vessels. After brachytherapy (143 +/-
      106 and 80 +/- 52 days for first and second vessels, respectively), ACh-induced
      vasoconstriction was significantly reduced. The ACh-induced changes in artery
      diameter before and after brachytherapy were -1.5 +/- 0.5 mm and -0.5 +/- 0.3 mm
      (p < 0.0001) for the first vessels and -1.4 +/- 0.3 mm and -0.4 +/- 0.2 mm (p <
      0.01) for the second vessels, respectively. In non-irradiated spastic vessels,
      ACh-induced vasoconstriction remained unchanged (e.g., -1.7 +/- 0.6 mm, -1.6 +/-
      0.3 mm, and -1.5 +/- 0.5 mm for second vessels, at first investigation, first
      follow-up, and immediately before brachytherapy, respectively). Angina frequency
      decreased from 15.6 +/- 6.0 to 2.2 +/- 2.4 angina episodes/week (p < 0.001) in
      treated patients. CONCLUSIONS: Brachytherapy is a potential therapy in patients
      with highly symptomatic variant angina.

PMID- 15464322
TI  - Identification of less-irradiating tube angulations in invasive cardiology.
AB  - OBJECTIVES: We sought to identify tube angulations in invasive cardiology, which
      promise minimal radiation exposure to patients and operators. BACKGROUND:
      Radiation exposure in invasive cardiology is high. METHODS: We mapped the
      fluoroscopic dose-area product per second (DAP/s), applied to an anthropomorphic
      Alderson-Rando phantom and, in absence of radiation protection devices, the mean
      personal dose in the operator's position in 10 degrees steps from the 100 degrees
      right anterior oblique (RAO) to the 100 degrees left anterior oblique (LAO)
      projection, as well as for all geometrically feasible craniocaudal tube
      angulations. RESULTS: For our specific setting conditions RAO 20 degrees /0
      degrees tube angulation generated the lowest DAP/s and operator's personal dose.
      The mean patient DAP/s and operator personal dose for all postero-anterior (PA)
      projections, cranialized and caudalized together, rose significantly: 3.7 and
      10.6 times the PA 0 degrees baseline values toward LAO 100 degrees and 3.7 and
      2.4 times toward RAO 100 degrees , respectively. Patient and operator values for
      all PA projections, angulated to the right and left, increased approximately 2.5
      times toward 30 degrees craniocaudal angulations. Caudal PA 0 degrees /30 degrees
      - angulation instead of caudal LAO 60 degrees /20 degrees - angulation for the
      left coronary main stem and cranial PA 0 degrees /30 degrees + view in place of
      cranial LAO 60 degrees /20 degrees + view for the left anterior descending
      coronary artery bifurcation enable 2.6-fold dose reductions to the patient and
      eight- and five-fold dose reductions to the operator, respectively. CONCLUSIONS:
      The PA views and RAO views >or=40 degrees , heretofore unconventional in clinical
      routine, should be favored over steep LAO projections >or=40 degrees whenever
      possible. Tube angulations that are radiation intensive to the patient
      exponentially increase the operator's radiation risk.

PMID- 15464323
TI  - A novel apoA-I mutation (L178P) leads to endothelial dysfunction, increased
      arterial wall thickness, and premature coronary artery disease.
AB  - OBJECTIVES: We investigated the consequences of an apolipoprotein A-I (apoA-I)
      gene defect with regard to lipid metabolism, endothelial function, arterial wall
      thickness, and coronary artery disease (CAD) risk. BACKGROUND: Due to limited
      numbers of carriers of the apoA-I defects, data on the consequences of such
      defects have remained inconclusive. METHODS: Lipids and lipoproteins were
      measured in 54 apoA-I (L178P) carriers and 147 nonaffected siblings. Flow
      mediated dilation (FMD) was assessed in 29 carriers and 45 noncarriers, and
      carotid intima-media thickness (IMT) could be determined in 33 heterozygotes and
      40 controls. Moreover, CAD risk was evaluated for all apoA-I mutation carriers.
      RESULTS: Heterozygotes exhibited lower plasma levels of apoA-I (-50%; p < 0.0001)
      and high-density lipoprotein cholesterol (-63%; p < 0.0001). In addition,
      carriers had impaired FMD (p = 0.012) and increased carotid IMT (p < 0.001),
      whereas multivariate analysis revealed that heterozygotes had a striking 24-fold
      increase in CAD risk (p = 0.003). CONCLUSIONS: Heterozygosity for a novel apoA-I
      mutation underlies a detrimental lipoprotein profile that is associated with
      endothelial dysfunction, accelerated carotid arterial wall thickening, and
      severely enhanced CAD risk. Importantly, the extent of atherosclerosis in these
      subjects was similar to the burden of premature arterial wall abnormalities seen
      in patients with familial hypercholesterolemia. These data illustrate the pivotal
      role in humans of apoA-I in the protection against CAD.

PMID- 15464324
TI  - Apolipoprotein A-I and high-density lipoprotein: is this the beginning of the era
      of noninvasive angioplasty?

PMID- 15464325
TI  - Surgical ventricular restoration in the treatment of congestive heart failure due
      to post-infarction ventricular dilation.
AB  - OBJECTIVES: The purpose of this study was to test how surgical ventricular
      restoration (SVR) affects early and late survival in a registry of 1,198 post
      anterior infarction congestive heart failure (CHF) patients treated by the
      international Reconstructive Endoventricular Surgery returning Torsion Original
      Radius Elliptical shape to the left ventricle (RESTORE)team. BACKGROUND:
      Congestive heart failure may be caused by late left ventricular (LV) dilation
      after anterior infarction. The infarcted segment is often akinetic rather than
      dyskinetic because early reperfusion prevents transmural necrosis. Previously,
      only dyskinetic areas were treated by operation. Surgical ventricular restoration
      reduces LV volume and creates a more elliptical chamber by excluding scar in
      either akinetic or dyskinetic segments. METHODS: The RESTORE group applied SVR to
      1,198 post-infarction patients between 1998 and 2003. Early and late outcomes
      were examined, and risk factors were identified. RESULTS: Concomitant procedures
      included coronary artery bypass grafting in 95%, mitral valve repair in 22%, and
      mitral valve replacement in 1%. Overall 30-day mortality after SVR was 5.3% (8.7%
      with mitral repair vs. 4.0% without repair; p < 0.001). Perioperative mechanical
      support was uncommon (<9%). Global systolic function improved postoperatively.
      Ejection fraction (EF) increased from 29.6 +/- 11.0% preoperatively to 39.5 +/-
      12.3% postoperatively (p < 0.001). The left ventricular end-systolic volume index
      (LVESVI) decreased from 80.4 +/- 51.4 ml/m(2) preoperatively to 56.6 +/- 34.3
      ml/m(2) postoperatively (p < 0.001). Overall five-year survival was 68.6 +/-
      2.8%. Logistic regression analysis identified EF <or=30%, LVESVI >or=80 ml/m(2),
      advanced New York Heart Association (NYHA) functional class, and age >or=75 years
      as risk factors for death. Five-year freedom from hospital readmission for CHF
      was 78%. Preoperatively, 67% of patients were NYHA functional class III or IV and
      postoperatively, 85% were class I or II. CONCLUSIONS: Surgical ventricular
      restoration improves ventricular function and is highly effective therapy in the
      treatment of ischemic cardiomyopathy with excellent five-year outcome.

PMID- 15464326
TI  - Outcomes in heart failure patients after major noncardiac surgery.
AB  - OBJECTIVES: The purpose of this study was to evaluate mortality and readmission
      rates of heart failure (HF) patients after major noncardiac surgery. BACKGROUND:
      There is a lack of generalizable outcome data on HF patients undergoing major
      noncardiac surgery because previous studies have been limited to a few academic
      centers or have not focused on this group of patients. METHODS: Using the 1997 to
      1998 Standard Analytic File 5% Sample of Medicare beneficiaries, we identified
      patients with HF who underwent major noncardiac surgery. A multivariable logistic
      regression model was used to provide adjusted mortality and readmission rates in
      patients after noncardiac surgery. Patients with coronary artery disease (CAD)
      and all other remaining patients (Control) who had similar surgery served as
      reference groups. RESULTS: Of 23,340 HF patients and 28,710 CAD patients, 1,532
      (6.56%) HF patients and 1,757 (6.12%) CAD patients underwent major noncardiac
      surgery. There were 44,512 patients in the Control group with major noncardiac
      surgery. After accounting for demographic characteristics, type of surgery, and
      comorbid conditions, the risk-adjusted operative mortality (death before
      discharge or within 30 days of surgery) was HF 11.7%, CAD 6.6%, and Control 6.2%
      (HF vs. CAD, p < 0.001; CAD vs. Control, p = 0.518). The risk-adjusted 30-day
      readmission rate was HF 20.0%, CAD 14.2%, and Control 11.0% (p < 0.001).
      CONCLUSIONS: In patients 65 years of age and older, HF patients undergoing major
      noncardiac surgery suffer substantial morbidity and mortality despite advances in
      perioperative care, whereas patients with CAD without HF have similar mortality
      compared with a more general population.

PMID- 15464327
TI  - Ultrasound energy improves myocardial perfusion in the presence of coronary
      occlusion.
AB  - OBJECTIVES: We evaluated whether ultrasound improves myocardial tissue perfusion
      in 14 animals with coronary artery occlusion. BACKGROUND: A recent study
      demonstrated that low-frequency ultrasound improves tissue perfusion in the
      rabbit ischemic limb, but there are no data on ultrasound enhancement of
      myocardial perfusion. METHODS: Fourteen animals (9 dogs, 5 pigs) underwent
      thoracotomy and occlusion of a diagonal branch of the left anterior descending
      coronary artery. Myocardial tissue perfusion units (TPUs) and pH were measured
      before coronary occlusion, after occlusion, and after direct exposure of the
      ischemic myocardium in the presence of fixed occlusion to low-frequency
      ultrasound (27 kHz). RESULTS: The TPU decreased from 100.9 +/- 13 at baseline to
      71.1 +/- 13 (p < 0.01) after 60 min occlusion but rose by 19.7% to 85.1 +/- 8 (p
      < 0.01) after ultrasound exposure for 60 min. After 60-min coronary occlusion,
      myocardial pH fell from 7.43 +/- 14 to 7.05 +/- 0.15 (p < 0.01) but then improved
      to normal (7.46 +/- 0.32) after ultrasound for 60 min. Administration of L-Nomega
      nitro-arginine methyl esther (L-NAME), an inhibitor of nitric oxide synthase,
      before ultrasound exposure, blocked improvement in myocardial tissue perfusion
      and pH by ultrasound. Quantitative histomorphology showed a significant increase
      in the capillary area of myocardium exposed to ultrasound versus non-exposed
      myocardium (16.2 +/- 7.9 vs. 8.2 +/- 2.1, p < 0.02). CONCLUSIONS: Low-frequency,
      low-intensity ultrasound improves myocardial tissue perfusion and pH in the
      presence of a fixed coronary artery occlusion.

PMID- 15464328
TI  - Tissue Doppler-derived myocardial acceleration for evaluation of left ventricular
      diastolic function.
AB  - OBJECTIVES: Our purpose was to evaluate a tissue Doppler-based index-peak
      myocardial acceleration (pACC)-during isovolumic relaxation and in evaluating
      left ventricular (LV) diastolic function. BACKGROUND: Simple, practical indexes
      for diastolic function evaluation are lacking, but are much desired for clinical
      evaluation. METHODS: We examined eight sheep by using tissue Doppler ultrasound
      images obtained in the apical four-chamber views to evaluate mitral valve annular
      velocity at the septum and LV wall. The pACC thus derived was analyzed during
      isovolumic relaxation (IVRT) and during the LV filling period (LVFP). We then
      changed the hemodynamic status of each animal by blood administration,
      dobutamine, and metoprolol infusion. We compared the pACC values during IVRT and
      LVFP over the four different hemodynamic conditions with a peak rate of drop in
      LV pressure (-dP/dt(min)) and the time constant of LV isovolumic pressure decay
      (tau), as measured with a high-frequency manometer-tipped catheter. RESULTS: The
      pACC of the septal side of the mitral valve annulus during IVRT showed a good
      correlation with -dP/dt(min) (r = -0.80, p < 0.0001) and tau (r = -0.87, p <
      0.0001). The mean left atrial pressure (LAP) correlated well with the septal side
      pACC during LVFP (r = 0.81, p < 0.0001). There was a weak correlation between the
      mitral valve annulus pACC at the LV lateral wall and mean LAP. CONCLUSIONS: The
      pACC during IVRT is a sensitive, preload-independent marker for evaluation of LV
      diastolic function. In addition, pACC during LVFP correlated well with mean LAP.

PMID- 15464329
TI  - Prevalence and severity of paravalvular regurgitation in the Artificial Valve
      Endocarditis Reduction Trial (AVERT) echocardiography study.
AB  - OBJECTIVES: The purpose of this study was to determine the prevalence and
      severity of paravalvular regurgitation (PVR) in the Artificial Valve Endocarditis
      Reduction Trial (AVERT) cohort. BACKGROUND: The initial AVERT cohort consisted of
      807 patients randomized to receive either a Silzone-coated prosthetic valve or a
      conventional prosthetic valve; early clinical reports showed higher rates of
      valve explant caused by PVR for Silzone-coated prosthetic valve. METHODS: Of the
      678 eligible patients, 575 (85%) underwent postoperative transthoracic
      echocardiograms. The presence and severity of PVR were identified by color flow
      Doppler. Reviewers were blinded to the type of prosthetic valve and the
      demographic and clinical variables. RESULTS: Among those who underwent
      echocardiography (Silzone-coated prosthetic valve, n = 285 and conventional
      prosthetic valve, n = 290), 59% had prosthetic aortic valves, 32% prosthetic
      mitral valves, and 9% had both; demographic and clinical findings (i.e.,
      prosthetic valve endocarditis, thromboembolism, bleeding, and all-cause death)
      were similar for the two groups. Echocardiographically determined PVR was present
      in 50 valves: Silzone-coated prosthetic valve, 29 of 285 (10%) and conventional
      prosthetic valve, 21 of 290 (7%, p = NS); the severity of PVR was similar in both
      groups. Kaplan-Meier analysis showed no significant differences in PVR at 24
      months from valve implantation between the two groups (24-month event-free rate:
      93% Silzone-coated prosthetic valve vs. 94% conventional prosthetic valve, p =
      NS). CONCLUSIONS: Excluding those patients who had initial prosthetic valve
      explant, the two-year echocardiographic follow-up of the AVERT cohort shows no
      statistically significant differences in the prevalence or severity of PVR in the
      Silzone-coated prosthetic valve compared with the conventional prosthetic valve.
      Further monitoring is warranted to determine whether these clinical outcomes
      remain similar on long-term follow-up.

PMID- 15464330
TI  - Quantitative hyperemic reactivity in opposed limbs during myocardial perfusion
      imaging: a new marker of coronary artery disease.
AB  - OBJECTIVES: We sought to evaluate the feasibility and validity of a new method to
      quantify the hyperemic response of the forearms that can be incorporated into a
      rest myocardial perfusion protocol. BACKGROUND: Evaluation of the hyperemic
      response could provide useful clinical information in the detection and risk
      stratification of atherosclerotic vascular disease. METHODS: Patients with proven
      coronary artery disease (CAD) (n = 46) were compared with low-risk subjects
      without such evidence (n = 47). A regular dose of Myoview was injected after 5
      min of right arm ischemia. Three dimensionless parametric ratios (right/left)
      were derived from the analysis of activity-time curves of the hyperemic right
      forearm and that of the contralateral left forearm. RESULTS: The maximal ingress
      upslope ratio was 40% lower in the CAD group (3.0 +/- 0.2 vs. 4.2 +/- 0.3, p <
      0.0005), and the integral to peak ratio was also lower (23 +/- 4 vs. 52 +/- 11, p
      < 0.01), whereas the peak activity ratio was nonsignificantly lower (3.0 +/- 0.3
      vs. 3.8 +/- 0.3, p = 0.07). Using a value of 3.55 for the maximal upslope ratio,
      this approach could predict the presence of CAD with a sensitivity of 0.70 and a
      specificity of 0.60. CONCLUSIONS: This simple and noninvasive method is feasible
      and can discriminate between patients with known CAD and those at low risk of
      atherosclerosis. Refinements of this approach and its inclusion in larger
      clinical trials are needed to determine whether it could provide additional value
      to myocardial scintigraphic imaging.

PMID- 15464331
TI  - A novel technique to assess flow-mediated vasodilation.

PMID- 15464332
TI  - QT interval variability and spontaneous ventricular tachycardia or fibrillation
      in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II
      patients.
AB  - OBJECTIVES: This study aimed to determine whether increased QT interval
      variability is associated with an increased risk for ventricular tachycardia (VT)
      or ventricular fibrillation (VF), documented by interrogation of the implantable
      cardioverter-defibrillator (ICD), in patients enrolled in the Multicenter
      Automatic Defibrillator Implantation Trial (MADIT) II. BACKGROUND: Unstable
      repolarization has been proposed as a risk factor for re-entrant arrhythmias, but
      confirmatory data from clinical trials are lacking. METHODS: The QT variability
      was assessed in 10-min, resting high-resolution electrocardiogram recordings at
      study entry using a semiautomated algorithm that measured beat-to-beat QT
      duration in 817 MADIT II patients. The incidence of VT/VF requiring device
      therapy was determined by ICD interrogation. RESULTS: Median normalized QT
      variability (QTVN) was 0.179 and 0.125, respectively, in patients with VT/VF
      versus those without VT/VF (p = 0.001); QTVI (QTVN adjusted for heart rate
      variance) also was significantly (p < 0.05) higher in VT/VF patients than in
      those without VT/VF. Either QTVN or QTVI was linked with a significantly higher
      probability of VT/VF: two-year risk of VT/VF from Kaplan-Meier curves was 40% in
      highest quartile versus 21% in lower quartiles for QTVN, and 37% versus 22% for
      QTVI (p < 0.05 for each). In multivariate Cox regression models adjusting for
      clinical covariates (race, New York Heart Association functional class, time
      after myocardial infarction), top-quartile QTVI and QTVN were independently
      associated with VT/VF (hazard ratio for QTVN 2.18, 95%confidence interval [CI]
      1.34 to 3.55, p = 0.002; hazard ratio for QTVI 1.80, 95% CI 1.09 to 2.95, p =
      0.021). CONCLUSIONS: In postinfarction patients with severe left ventricular
      dysfunction, increased QT variability, a marker of repolarization lability, is
      associated with an increased risk for VT/VF.

PMID- 15464333
TI  - Differences in hemodynamic and oxygenation responses to three different
      phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension:
      a randomized prospective study.
AB  - OBJECTIVES: We sought to compare the short-term impact of three different
      phosphodiesterase-5 (PDE5) inhibitors on pulmonary and systemic hemodynamics and
      gas exchange parameters in patients with pulmonary arterial hypertension (PAH).
      BACKGROUND: The PDE5 inhibitor sildenafil has been reported to cause pulmonary
      vasodilation in patients with PAH. Vardenafil and tadalafil are new PDE5
      inhibitors, recently being approved for the treatment of erectile dysfunction.
      METHODS: Sixty consecutive PAH patients (New York Heart Association functional
      class II to IV) who underwent right heart catheterization received short-term
      nitric oxide (NO) inhalation and were subsequently assigned to oral intake of 50
      mg sildenafil (n = 19), 10 mg (n = 7) or 20 mg (n = 9) vardenafil, or 20 mg (n =
      9), 40 mg (n = 8), or 60 mg (n = 8) tadalafil. Hemodynamics and changes in
      oxygenation were assessed over a subsequent 120-min observation period. RESULTS:
      All three PDE5 inhibitors caused significant pulmonary vasorelaxation, with
      maximum effects being obtained after 40 to 45 min (vardenafil), 60 min
      (sildenafil), and 75 to 90 min (tadalafil). Sildenafil and tadalafil, but not
      vardenafil, caused a significant reduction in the pulmonary to systemic vascular
      resistance ratio. Significant improvement in arterial oxygenation (equally to NO
      inhalation) was only noted with sildenafil. CONCLUSIONS: In PAH patients, the
      three PDE5 inhibitors differ markedly in their kinetics of pulmonary
      vasorelaxation (most rapid effect by vardenafil), their selectivity for the
      pulmonary circulation (sildenafil and tadalafil, but not vardenafil), and their
      impact on arterial oxygenation (improvement with sildenafil only). Careful
      evaluation of each new PDE5 inhibitor, when being considered for PAH treatment,
      has to be undertaken, despite common classification as PDE5 inhibitors.

PMID- 15464334
TI  - Pulmonary arteriovenous shunting in the normal fetal lung.
AB  - OBJECTIVES: We hypothesized that pulmonary arteriovenous shunting (PAVS) is
      normally present in fetal lungs and that cavopulmonary anastomosis-induced PAVS
      may represent a return to an earlier morphologic stage of development.
      BACKGROUND: The surgical superior cavopulmonary anastomosis is performed as part
      of the staged Fontan pathway to treat univentricular forms of congenital heart
      disease; PAVS is a known sequela after superior cavopulmonary anastomosis and may
      have important clinical consequences. Although the etiology and true morphology
      of the structures responsible for PAVS are unknown, a leading theory is that PAVS
      is caused by absence of normal hepatic venous drainage to the pulmonary
      circulation. METHODS: To determine whether normal fetal lungs demonstrate PAVS,
      we performed contrast echocardiograms on 13 fetal lambs, 8 neonatal lambs, 4
      juvenile lambs, and 4 adult sheep using a blended mixture of saline and blood
      injected directly into the proximal pulmonary artery. RESULTS: Pulmonary
      arteriovenous shunting was detected by direct epicardial echocardiography in all
      fetal lambs (n = 13) and neonatal animals studied at one and three days of life
      (n = 4) and in two of four animals studied at six to nine days of life. Pulmonary
      arteriovenous shunting was not present in animals studied at four weeks of life
      (n = 2) and in adult sheep (n = 5). CONCLUSIONS: These studies demonstrate that
      PAVS is normally present in late gestation fetal and early neonatal lambs but
      then disappears during the later neonatal period. Furthermore, these findings
      suggest that PAVS associated with cavopulmonary anastomosis or other processes
      affecting the developing pulmonary circulation may represent a return to an
      earlier morphologic stage of development.

PMID- 15464335
TI  - The effects of carbon dioxide on oxygenation and systemic, cerebral, and
      pulmonary vascular hemodynamics after the bidirectional superior cavopulmonary
      anastomosis.
AB  - OBJECTIVES: We investigated the effects of different CO(2) tensions on
      oxygenation, pulmonary blood flow (Qp), cerebral blood flow, and systemic blood
      flow (Qs) after the bidirectional superior cavopulmonary anastomosis (BCPA).
      BACKGROUND: Hypoxemia refractory to management of a high pulmonary vascular
      resistance index (PVRI) may complicate recovery from the BCPA. METHODS: After
      BCPA, CO(2) was added to the inspired gas of mechanically ventilated patients.
      The Qp, Qs, PVRI, and systemic vascular resistance index (SVRI) were calculated
      from oxygen consumption, intravascular pressures, and oxygen saturations.
      Cerebral blood flow was estimated by near infrared spectroscopy and transcranial
      Doppler. RESULTS: In nine patients (median age 7.1, range 2 to 23 months),
      arterial oxygen tension increased significantly (p < 0.005) from 36 +/- 6 mm Hg
      to 44 +/- 6 to 50 +/- 7 mm Hg at arterial carbon dioxide tensions (PaCO(2)) of
      35, 45, and 55 mm Hg, respectively and decreased to 40 +/- 8 mm Hg at PaCO(2) 40
      mm Hg. At a PaCO(2) of 55 and 45 compared with 35 mm Hg, Qp, cerebral blood flow,
      and Qs increased significantly, PVRI, Qp/Qs, and the ratio of Qp to inferior vena
      caval blood flow were unchanged, but SVRI decreased. CONCLUSIONS: We have
      demonstrated that after the BCPA, systemic oxygenation, Qp, Qs, and cerebral
      blood flow increased and SVRI decreased at CO(2) tensions of 45 and 55 mm Hg
      compared with 35 mm Hg. We suggest that hypoxemia after the BCPA is ameliorated
      by a higher PaCO(2) and that low PaCO(2) or alkalosis may be detrimental.
      Hypercarbic management strategies may allow earlier progression to the BCPA,
      which may contribute to reducing the interval morbidity in patients with a
      functional single ventricle.

PMID- 15464336
TI  - Effect of granulocyte-macrophage colony-stimulating factor inducer on left
      ventricular remodeling after acute myocardial infarction.
AB  - OBJECTIVES: We sought to determine the influence of granulocyte-macrophage colony
      stimulating factor (GM-CSF) induction on post-myocardial infarction (MI)
      remodeling, especially in relation to the inflammatory response and myocardial
      fibrosis. BACKGROUND: Granulocyte-macrophage colony-stimulating factor modifies
      wound healing by promoting monocytopoiesis and infiltration of monocytes and
      macrophages into injured tissue; however, the effect of GM-CSF induction on the
      infarct healing process and myocardial fibrosis is unclear. METHODS: A model of
      MI was produced in Wistar rats by ligation of the left coronary artery. The MI
      animals were randomized to receive GM-CSF inducer (romurtide 200 microg/kg/day
      for 7 consecutive days) (MI/Ro) or saline (MI/C). RESULTS: Echocardiographic and
      hemodynamic studies on day 14 revealed increased left ventricular (LV) end
      diastolic dimension, decreased fractional shortening, elevated LV end-diastolic
      pressure, and decreased LV maximum rate of isovolumic pressure development in
      MI/Ro compared with MI/C. Immunoblotting showed that expression of transforming
      growth factor (TGF)-beta1 in the infarcted site on day 3 after MI was decreased
      in MI/Ro compared with MI/C. In the infarcted site, TGF-beta1, collagen type I
      and type III messenger ribonucleic acid (mRNA) expression on day 3, and collagen
      content on day 7 were reduced in MI/Ro compared with MI/C, in association with
      marked infarct expansion. In MI/Ro, monocyte chemoattractant protein-1 mRNA level
      and the degree of infiltration of monocyte-derived macrophages (ED-1
      positive)were greater in the infarcted site on day 7 than those in MI/C.
      CONCLUSIONS: The GM-CSF induction by romurtide facilitated infarct expansion in
      association with the promotion of monocyte recruitment and inappropriate collagen
      synthesis in the infarcted region during the early phase of MI.

PMID- 15464337
TI  - Mobilizing cells to the injured myocardium: a novel rescue strategy or an
      unwelcome intrusion?

PMID- 15464338
TI  - President's page: Exercise your vote: Health care central to election 2004.

PMID- 15464340
TI  - High-protein diets: putting rumors to rest.

PMID- 15464342
TI  - Mechanism of a hypertensive response to exercise.

PMID- 15464343
TI  - Brain natriuretic peptide as a predictor of sudden cardiac death in patients with
      myocardial infarction.

PMID- 15464344
TI  - Does nondipping blood pressure profile contribute to vascular inflammation during
      sleep deprivation?

PMID- 15464347
TI  - Neuroimaging of interval timing.
AB  - Exactly how the brain is able to measure the durations of events lasting from
      seconds to minutes while maintaining time-scale invariance remains largely a
      mystery. Neuroimaging studies are only now beginning to unravel the nature of
      interval timing and reveal whether different timing mechanisms are required for
      the perception and production of sub- and supra-second intervals that can be
      defined by different stimulus modalities. We here review the impact that
      neuroimaging studies have had on the field of timing and time perception and
      outline the major challenges that remain to be addressed before a physiologically
      realistic theory of interval timing can be established involving cortico-striatal
      circuits.

PMID- 15464348
TI  - Cortico-striatal circuits and interval timing: coincidence detection of
      oscillatory processes.
AB  - Humans and other animals demonstrate the ability to perceive and respond to
      temporally relevant information with characteristic behavioral properties. For
      example, the response time distributions in peak-interval timing tasks are well
      described by Gaussian functions, and superimpose when scaled by the criterion
      duration. This superimposition has been referred to as the scalar property and
      results from the fact that the standard deviation of a temporal estimate is
      proportional to the duration being timed. Various psychological models have been
      proposed to account for such responding. These models vary in their success in
      predicting the temporal control of behavior as well as in the neurobiological
      feasibility of the mechanisms they postulate. A review of the major interval
      timing models reveals that no current model is successful on both counts. The
      neurobiological properties of the basal ganglia, an area known to be necessary
      for interval timing and motor control, suggests that this set of structures act
      as a coincidence detector of cortical and thalamic input. The hypothesized
      functioning of the basal ganglia is similar to the mechanisms proposed in the
      beat frequency timing model [R.C. Miall, Neural Computation 1 (1989) 359-371],
      leading to a reevaluation of its capabilities in terms of behavioral prediction.
      By implementing a probabilistic firing rule, a dynamic response threshold, and
      adding variance to a number of its components, simulations of the striatal beat
      frequency model were able to produce output that is functionally equivalent to
      the expected behavioral response form of peak-interval timing procedures.

PMID- 15464349
TI  - Frontal-striatal circuitry activated by human peak-interval timing in the supra
      seconds range.
AB  - Functional magnetic resonance imaging (fMRI) was used to measure the location and
      intensity of brain activations when participants time an 11-s signal duration.
      The experiment evaluated six healthy adult male participants who performed the
      peak-interval timing procedure in variants of stimulus modality (auditory or
      visual) and condition (foreground or background: i.e., whether the presence or
      absence of the stimulus is the signal to be timed). The complete experimental
      design called for each signal variant to be used across four behavioral tasks
      presented in the following order: control, timing+motor, timing, and motor. In
      the control task, participants passively experienced the stimuli. The
      timing+motor and timing tasks were preceded by five fixed-time training trials in
      which participants learned the 11-s signal they would subsequently reproduce. In
      the timing+motor task, participants made two motor responses centered around
      their subjective estimate of the criterion time. For the timing task,
      participants were instructed to time internally without making a motor response.
      The motor task had participants make two cued responses that were not determined
      by the participant's sense of the passage of time. Neuroimaging data from the
      timing+motor and timing tasks showed activation of the frontal cortex, striatum
      and thalamus--none of which was apparent in the control or motor tasks. These
      results, combined with other peak-interval procedure data from drug and lesion
      studies in animals as well as behavioral results in human patient populations
      with striatal damage, support the involvement of frontal-striatal circuitry in
      human interval timing.

PMID- 15464350
TI  - Neural systems supporting timing and chronometric counting: an FMRI study.
AB  - At least two strategies are available to humans for estimating multisecond
      intervals. One depends on an interval timing system that is common to many
      species. The other is the language-based strategy of chronometric counting. These
      two strategies are easily distinguished by the psychophysical properties of their
      behavioral correlates: counting supports substantially more precise estimates
      than are possible using the more general interval timing system. The present
      study investigates the neural systems that underlie the execution of these
      different strategies. Eighteen adults reproduced a 16-s interval either by
      internally timing or covertly counting the duration. Comparison of counting and
      timing to a resting baseline suggested that these strategies engage some
      nonoverlapping neural systems. Counting, but not timing, strongly activated
      Broca's area, primary motor cortex in the mouth region, and right cerebellum, all
      of which are associated with internal speech. Counting also activated parts of
      the medial premotor circuit, including the putamen, supplementary motor area
      (SMA) proper, and cingulate motor area (CMA), that have been associated with
      reproducing isochronous and syncopated rhythms of elements lasting hundreds of
      milliseconds. During timing, only a portion of this circuit, the SMA proper and
      CMA, was engaged. Both timing and counting interfered with semantic processing
      during the resting state, evidenced by task-related decreases in the left
      inferior and middle frontal gyri, right superior frontal gyrus, left angular
      gyrus, and bilateral posterior cingulate cortex. This study suggests that
      counting activates a corticostriatal network associated with millisecond,
      rhythmic timing. In contrast, timing long durations without the benefit of
      linguistic strategies for subdividing counts reduces activity in this circuitry.

PMID- 15464351
TI  - Neural representation of interval encoding and decision making.
AB  - Our perception of time depends on multiple psychological processes that allow us
      to anticipate events. In this study, we used event-related functional magnetic
      resonance imaging (fMRI) to differentiate neural systems involved in formulating
      representations of time from processes associated with making decisions about
      their duration. A time perception task consisting of two randomly presented
      standard intervals was used to ensure that intervals were encoded on each trial
      and to enhance memory requirements. During the encoding phase of a trial,
      activation was observed in the right caudate nucleus, right inferior parietal
      cortex and left cerebellum. Activation in these regions correlated with timing
      sensitivity (coefficient of variation). In contrast, encoding-related activity in
      the right parahippocampus and hippocampus correlated with the bisection point and
      right precuneus activation was associated with a measure of memory distortion.
      Decision processes were studied by examining brain activation during the decision
      phase of a trial that was associated with the difficulty of interval
      discriminations. Activation in the right parahippocampus was greater for easier
      than harder discriminations. In contrast, activation was greater for harder than
      easier discriminations in systems involved in working memory (left middle-frontal
      and parietal cortex) and auditory rehearsal (left inferior-frontal and superior
      temporal cortex). Activity in the auditory rehearsal network correlated with
      memory distortion. Our results support the independence of systems that mediate
      interval encoding and decision processes. The results also suggest that
      distortions in memory for time may be due to strategic processing in cortical
      systems involved in either encoding or rehearsal.

PMID- 15464352
TI  - Timing functions of the supplementary motor area: an event-related fMRI study.
AB  - Two previous studies in which we recorded slow brain potential shifts over the
      scalp revealed performance-dependent effects that sustained one prominent model
      of timing mechanisms. These effects seemed to be derived from the supplementary
      motor area (SMA). Event-related functional magnetic resonance imagery (fMRI) was
      used to check this hypothesis. Brain activations were contrasted in Time
      production and (control) Force production tasks involving left-hand responding.
      These tasks, presented in mixed order, were designed to be of equivalent
      difficulty and involve comparable levels of attention. Several brain areas were
      activated in both tasks relative to baseline: the SMA, the putamen, and the
      lateral cerebellum. Contrasts between tasks gave clear-cut differences.
      Activations specific to the Time task were found in the SMA proper and the left
      primary motor cortex. The Force task activated the right sensorimotor cortex and
      the left cerebellum, and, bilaterally, the infero-parietal cortex and the insula.
      The main result, i.e. prominent activation of the SMA proper in relation to
      temporal production, corroborates our previous studies based on slow cortical
      potentials. The data are referred to current evidence suggesting that timing
      processes are subtended by a striato-thalamo-cortical pathway including the SMA.

PMID- 15464353
TI  - fMRI studies of temporal attention: allocating attention within, or towards,
      time.
AB  - Attention is distributed in time as well as space. Moreover, attention can be
      actively directed both within, and towards, time. This review article summarises
      behavioural and neuroanatomical correlates of temporal aspects of attention.
      Orienting attention to particular moments in time, or selectively attending to
      temporal rather than non-temporal stimulus features, improves behavioural
      measures of performance. These effects are accompanied by specific increases in
      activity of functionally specialised, and anatomically discrete, brain regions.
      Left parietal cortex is associated with orienting attention to specific moments
      in time. Pre-supplementary motor area (SMA) is associated with selectively
      attending to, and estimating, time. Frontal operculum is associated with all of
      these processes as well as being activated when attentional resources are limited
      by time itself. The frontal operculum therefore plays a pivotal role in the multi
      faceted interaction between time and attention.

PMID- 15464354
TI  - Timing in the baby brain.
AB  - Ten-month-old infants and adults were tested in an auditory oddball paradigm in
      which 50-ms tones were separated by 1500 ms (standard interval) and occasionally
      500 ms (deviant interval). Both infants and adults showed marked brain responses
      to the tone that followed a deviant inter-stimulus interval (ISI). Specifically,
      the timing-deviance event-related-potential (ERP) difference waves (deviant-ISI
      ERP minus standard-ISI ERP) yielded a significant, fronto-centrally distributed,
      mismatch negativity (MMN) in the latency range of 120-240 ms post-stimulus for
      infants and 110-210 ms for adults. A robust, longer latency, deviance-related
      positivity was also obtained for infants (330-520 ms), with a much smaller and
      later deviance-related positivity observed for adults (585-705 ms). These results
      suggest that the 10-month-old infant brain has already developed some of the same
      mechanisms as adults for detecting deviations in the timing of stimulus events.

PMID- 15464355
TI  - Electrophysiological correlates of interval timing in the Stop-Reaction-Time
      task.
AB  - Scalp-recorded event-related potentials were recorded while participants
      completed an auditory or a visual Stop-Reaction-Time task (Stop-RT task).
      Participants were asked to listen to a sequence of tones (Experiment 1) or view a
      sequence of LED flashes (Experiment 2) that had a constant stimulus onset
      asynchrony (SOA) of either 470 or 770 ms, and to respond as soon as the sequence
      ended. Sequence length varied across trials, so counting the tones or light
      flashes did not permit determination of sequence end. Instead, participants had
      to time the SOA, even though they were not explicitly instructed to do so, and
      respond when the SOA had been exceeded. At sequence end, a biphasic negative
      positive ERP response was emitted following the point in time when a stimulus
      would have occurred had the sequence continued. The negative component of this
      omission potential (OP) had a right fronto-central focus, whereas the positive
      component had a parietal focus; a pattern that held across SOA duration and
      signal modality. Moreover, the mean peak latency of the negative OP was
      equivalent in the visual and auditory modalities, even though the behavioral Stop
      RTs obtained in the auditory experiment were 200 ms faster than those obtained in
      the visual experiment. The amodal negative OP appears to be a correlate of an
      interval-timing process that precedes response initiation, whereas the positive
      OP is most likely a target P300.

PMID- 15464356
TI  - What is common to brain activity evoked by the perception of visual and auditory
      filled durations? A study with MEG and EEG co-recordings.
AB  - EEG and MEG scalp data were simultaneously recorded while human participants were
      performing a duration discrimination task in visual and auditory modality,
      separately. Short durations were used ranging from 500 to 900 ms, among which
      participants had to discriminate a previously memorized 700-ms "standard"
      duration. Behavioral results show accurate but variable performance within and
      between participants with expected modality effects: the percentage of responses
      was greater and the mean response time was shorter for auditory than for visual
      signals. Sustained electric and magnetic activities were obtained correlatively
      to duration estimation, but with distinct spatiotemporal properties. Electric CNV
      like potentials showed fronto-central negativity in both modalities, whereas
      magnetic sustained fields were distributed with respect to the modality of the
      interval to be timed. Time courses of these slow brain activities were found to
      be dependent on stimulus duration but not on its modality nor on the recording
      signal (EEG or MEG). Source reconstruction demonstrated that these sustained
      potentials/fields were generated by superimposed contributions from visual and
      auditory cortices (sustained sensory responses, SSR) and from prefrontal and
      parietal regions. By using these two complementary techniques, we thus
      demonstrated the involvement of frontal and parietal cerebral cortex in human
      timing.

PMID- 15464357
TI  - Timing speech: a review of lesion and neuroimaging findings.
AB  - Time is a fundamental dimension of behavior and as such underlies the perception
      and production of speech. This paper reviews patient and neuroimaging studies
      that investigated brain structures that support temporal aspects of speech. The
      left-frontal cortex, the basal ganglia, and the cerebellum represent structures
      that have been implicated repeatedly. A comparison with the structures involved
      in the timing of non-speech events (e.g., tones, lights, finger movements)
      suggests both commonalities and differences: while the basal ganglia and the
      cerebellum contribute to the timing of speech and non-speech events, the
      contribution of left-frontal cortex seems to be specific to speech or rapidly
      changing acoustic information. Motivated by these commonalities and differences,
      this paper presents assumptions about the function of basal ganglia, cerebellum,
      and cortex in the timing of speech.

PMID- 15464358
TI  - From the Editor's desk.

PMID- 15464359
TI  - Endostatin/collagen XVIII--an inhibitor of angiogenesis--is expressed in
      cartilage and fibrocartilage.
AB  - Aim of the study was to get a deeper insight in the mechanisms regulating
      avascularity of cartilaginious tissues. In the center of our interest was the
      expression of the anti-angiogenic fragment of collagen XVIII and its potency to
      inhibit angiogenesis. We observed a strong endostatin/collagen XVIII production
      in articular and fibrocartilage and an inhibitory potency concerning the VEGF
      signalling pathway. INTRODUCTION: Cartilaginous tissue is mainly avascular and
      shows a limited intrinsic capacity for healing. Aim of this study was to
      investigate the expression of the antiangiogenic peptide endostatin/collagen
      XVIII in cartilage and fibrocartilage. RESULTS: In fetal epiphyseal cartilage of
      humans high endostatin/collagen XVIII levels could be detected by ELISA whereas
      significantly lower levels were found in articular cartilage of adults. In the
      fibrocartilaginous tissue of the menisci, there was no significant difference in
      the endostatin/collagen XVIII concentrations between samples of fetuses and
      adults. But in the menisci of adults, endostatin/collagen XVIII concentrations
      were higher in the internal avascular two thirds of the meniscus whereas in the
      fetal menisci higher endostatin/collagen XVIII concentrations were found in the
      external third. Endostatin/collagen XVIII immunostaining of rat articular
      cartilage shows that endostatin/collagen XVIII downregulation starts soon after
      birth. In fetal cartilage and fibrocartilage of rats and humans,
      endostatin/collagen XVIII could be immunostained in the extracellular matrix and
      in the pericellular matrix of endothelial cells, fibrochondrocytes and
      chondrocytes. In adult cells, weak endostatin/collagen XVIII immunostaining was
      restricted to the pericellular matrix of fibrochondrocytes and chondrocytes. The
      detection of endostatin/collagen XVIII could be verified by in situ
      hybridization. Chondrocytes in vitro released measurable amounts of
      endostatin/collagen XVIII into culture supernatants. Stimulation of chondrocytes
      with EGF, as an example of a growth factor, or dexamethasone had no influence on
      endostatin/collagen XVIII expression. Endostatin inhibited VEGF-induced
      phosphorylation of MAPK in chondrocytes. CONCLUSIONS: The spatial and temporal
      expression of endostatin/collagen XVIII in cartilaginous tissue and its potency
      regarding inactivation of VEGF signalling suggests that this antiangiogenic
      factor is important not only for the development but also for the maintenance of
      avascular zones in cartilage and fibrocartilage. EXPERIMENTAL PROCEDURES: We
      analyzed the spatial and temporal expression of endostatin/collagen XVIII--an
      endogenous angiogenesis inhibiting factor--in cartilage and fibrocartilage of
      humans and rats by immunohistochemical and biochemical (ELISA) methods and by in
      situ hybridization. To elucidate possible factors responsible for the induction
      or suppression of endostatin/collagen XVIII in cartilaginous tissues,
      chondrocytes (cell line C28/I2) were exposed to EGF and dexamethason. To study
      the possible interaction of endostatin/collagen XVIII with angiogenic factors,
      the immortalized human chondrocytes (C28/I2) have been incubated with VEGF and
      the phosphorylation of the MAPK Erk 1/2 (extracellular-regulated kinases), a
      known signal transduction pathway for VEGF has been determined under the
      influence of endostatin.

PMID- 15464360
TI  - Expression and localization of reelin in human odontoblasts.
AB  - Reelin is a large extracellular matrix (ECM) glycoprotein strongly expressed
      during embryonic development in the central nervous system and involved in
      architectonic brain development. It could participate in axon plasticity
      processes or adhesion-recognition between nerve fibers in adulthood. Previously
      identified from a subtractive cDNA library of fully differentiated human
      odontoblasts, reelin might be involved in the relationship between dental nerves
      and odontoblasts in as so far the latter are in close association with pulpal
      nerve fibers. Here, we show by in situ hybridization and immunohistochemistry
      that reelin is specifically expressed by human odontoblasts in vivo and in vitro
      and that an intense expression of the reelin gene is detected in odontoblasts in
      comparison with pulpal cells (PC). Co-cultures of rat trigeminal ganglion (TG)
      and odontoblasts allow to mimic odontoblast innervation and demonstrate that
      neurites contact these cells with reelin molecules as observed in vivo in human
      dental pulp. Moreover, by RT-PCR, we show that both reelin receptors (namely
      apolipoprotein E receptor [ApoER-2], very low density lipoprotein receptor
      [VLDLR] and cadherin-related neuronal receptor [CNR]) and the cytoplasmic adapter
      Disabled-1 implicated in the reelin signal transduction, were expressed by
      trigeminal ganglion. On the basis of these data, we suggest that reelin might be
      an extracellular matrix molecule involved in the terminal innervation of the
      dentin-pulp complex, promoting adhesion between dental nerve endings and
      odontoblasts.

PMID- 15464362
TI  - A transcriptional profile of human fetal cartilage.
AB  - Cartilage plays a central role in the patterning and growth of the skeletal
      elements, and mutations in genes expressed in cartilage are responsible for at
      least 250 distinct clinical conditions, the osteochondrodysplasias. While recent
      progress has been made in characterizing the genes that define cartilage biology,
      there are only limited data describing the gene expression profile of human
      cartilage. Here we describe the sequences and identities of 6266 clones from an
      18-20-week human fetal cartilage cDNA library. Among the sequences, BLAST
      analysis identified 2404 individual transcripts. Of these, 1775 were defined as
      derived from characterized genes and the remaining 629 were classified as
      representing the products of uncharacterized genes. Analysis of the relative
      representation of each individual transcript showed that the 186 most abundant
      cDNAs in the library accounted for almost half (47.7%) of the clones. The most
      highly expressed gene was COL2A1, accounting for 4.15% of all cDNA clones. The
      cDNAs identified included clones derived from 27 genes which, when mutated,
      result in disorders of skeletal patterning, development and growth. There were
      cDNAs representing 22 genes encoding collagen subunits. The genes encoding the
      identified cDNAs represent candidates for the approximately 100
      osteochondrodysplasias for which the causative gene has not yet been identified.
      Moreover, these data provide an extensive profile of human fetal cartilage gene
      expression at this developmental stage.

PMID- 15464361
TI  - Lp3/Hapln3, a novel link protein that co-localizes with versican and is
      coordinately up-regulated by platelet-derived growth factor in arterial smooth
      muscle cells.
AB  - Link proteins (LPs) belong to the link-module superfamily, which can stabilize
      and enhance the binding of lecticans to hyaluronan. We report here the
      identification and characterization of a novel rat link protein gene
      (Lp3/Hapln3). The deduced protein sequence shares the typical modular elements of
      link proteins and has an estimated mass of 39 kDa. Examination of the rat genomic
      DNA sequence revealed that Lp3/Hapln3 and aggrecan genes were paired on
      chromosome 1q31. Another LP gene and the lectican gene were also paired at a
      different locus, as they are in the human and mouse genomes. Immunohistochemical
      analysis showed the prominent expression of Lp3/Hapln3 in the smooth muscle
      tissues of the vascular wall and gastrointestinal tract. Further comparative
      studies revealed that Lp3/Hapln3 was well co-localized with versican around the
      smooth muscle cells of blood vessels but not around endothelial cells. In vitro
      experiments using primary cultured rat arterial smooth muscle cells (ASMCs)
      demonstrated the coordinated up-regulation of Lp3/Hapln3 and versican by platelet
      derived growth factor (PDGF). These data were supported by in vivo studies of a
      mechanical vascular injury model in mice. Altogether, our results suggest that
      Lp3/Hapln3 is involved, together with versican and hyaluronan, in the formation
      of the pericellular matrix of vascular smooth muscle cells.

PMID- 15464363
TI  - A highly conserved enhancer in mammalian type X collagen genes drives high levels
      of tissue-specific expression in hypertrophic cartilage in vitro and in vivo.
AB  - Previously we have identified a cis-acting regulatory domain in the human type X
      collagen gene upstream of the transcription start site which acts as a strong
      enhancer in hypertrophic, but not in resting chondrocytes. Here we show that this
      enhancer is highly conserved also in the murine and bovine Col10a1 genes, but not
      found in the known promoter sequences of chicken Col10a1. It contains a
      functionally active AP-1 site (TPA Responsive Element, TRE) which is essential
      for the high transcriptional activity of the COL10A1 enhancer in transiently
      transfected hypertrophic chondrocytes. Gel-shift experiments with nuclear
      extracts of hypertrophic chondrocytes revealed FosB and Fra-1 as candidates
      regulating AP-1 factors binding to the TRE site. In fact, coexpression of FosB
      and Fra-1 in reporter gene assays greatly stimulated transcriptional activity of
      enhancer bearing reporter genes. Quantitative analysis of AP-1 factor mRNA levels
      in distinct fractions of fetal bovine epiphyseal chondrocytes by real-time PCR
      confirmed significant levels of FosB and Fra-1 mRNA besides other AP-1 factors in
      hypertrophic chondrocytes. A key role of the enhancer element in regulating
      tissue-specific expression of the Col10a1 gene was shown by establishing
      transgenic mouse lines with a reporter gene containing a 4.6 kb murine Col10a1
      promoter fragment which included the enhancer, exon 1, part of exon 2 and the
      first intron. Reporter gene expression was seen exclusively in hypertrophic
      cartilages in the growth plates of long bones, ribs, vertebrae, sternum and
      mandibles of 17.5-18.5 dpc embryos, confirming that the 4.6 kb promoter is able
      to drive specific expression of Col10a1 in hypertrophic cartilage. These
      established transgenic lines should facilitate the genetic analysis of regulatory
      pathways of chondrocyte maturation and Col10a1 gene expression in the future.

PMID- 15464364
TI  - The combined regulation of estrogen and cyclic tension on fibroblast biosynthesis
      derived from anterior cruciate ligament.
AB  - Female athletes are two to eight times more likely to suffer a knee or ankle
      ligament injury than male athletes, and sex hormones have been considered to play
      an important role in the injury. Because ligaments are always under mechanical
      loading during sports, mechanical force is also a critical factor in ligament
      injuries. In this study, the effects of estrogen and mechanical loading on the
      gene expression of three major components of ligament--collagen type I, type III,
      and biglycan--in primary cultured porcine anterior cruciate ligament (ACL)
      fibroblasts were investigated individually and collectively using reverse
      transcript-polymerase chain reaction (RT-PCR). The results revealed that cyclic
      tensile loading alone increased the messenger RNA expression of collagen I but
      did not affect that of collagen III and biglycan, and estrogen alone increased
      the gene expression of collagen I and III but not of biglycan. However, combined
      administration of estrogen and cyclic loading inhibited the mRNA expression of
      all the three genes. These results suggested that the inhibition of the gene
      expression of major extracellular matrix component molecules caused by the
      combined effects of estrogen and mechanical loading, unique to females, might be
      responsible for the increased incidence of ligaments injury in female athletes.

PMID- 15464365
TI  - Tissue and cell engineering.

PMID- 15464366
TI  - Approaches for trigger-inducible viral transgene regulation in gene-based tissue
      engineering.
AB  - Recent advances in mammalian transgene expression dosing have resulted in a
      portfolio of mutually compatible systems that can adjust therapeutic transgene
      levels in response to antibiotics, hormone analogues, quorum-sensing messengers
      and secondary metabolites. The molecular merger of trigger-inducible expression
      technology with the latest generation of virus-derived transduction systems has
      enabled unmatched clinical interventions to shape desired therapeutic cell and
      tissue phenotypes for the treatment of complex human diseases.

PMID- 15464367
TI  - Protein-based tissue engineering in bone and cartilage repair.
AB  - Bioactive proteins signal host or transplanted cells to form the desired tissue
      type. Matrix systems are utilized to locally deliver the proteins and to maintain
      effective protein concentrations. For some indications, a matrix is required to
      define the physical form of the regenerated tissue. Substantial progress has been
      made in bone tissue engineering in recent years, based on the results of
      controlled clinical studies using bone morphogenetic proteins. Ongoing research
      in this area centers on the design of additional delivery matrices to expand the
      clinical indications, using synthetic delivery systems that mimic biological
      qualities of the natural materials currently in use. Although a similar rationale
      exists for the regeneration of articular cartilage with bioactive factors,
      advancement in this area has not been as substantial.

PMID- 15464368
TI  - Protein- and gene-based tissue engineering in bone repair.
AB  - A tissue engineering approach to bone regeneration includes the use of a
      scaffold, cells and bioactive factors alone or in various combinations. Several
      investigators have demonstrated enhanced bone formation when the tissue
      engineered construct possesses traits inherent to autogenic bone grafts, namely
      osteoconductivity, osteoinductivity and osteogenicity. Use of the biodegradable
      polymer poly(lactide-co-glycolide) in combination with bone morphogenetic protein
      or primary cells genetically modified to release osteogenic protein have
      demonstrated the ability to induce osteogenic differentiation of, and subsequent
      mineralization by, muscle-derived cells and mesenchymal stem cells in both in
      vitro and in vivo applications.

PMID- 15464369
TI  - Tissue engineering through autologous mesenchymal stem cells.
AB  - The regeneration of damaged cartilage in different pathological situations is a
      major goal for the future and could be achieved through cell and/or gene therapy.
      Mesenchymal stem cells (MSCs) are the progenitors of multiple lineages, including
      bone, cartilage, muscle, fat, and astrocytes. MSCs seem to be the best candidates
      for cell therapy to regenerate injured tissue, as they are easily isolated from
      bone marrow and can be rapidly amplified. Full healing is extremely demanding,
      however, and includes integration of the regenerated tissue within the
      surrounding host tissue and true differentiation through pathways involved in
      embryonic development. This goal might be reached through the combined use of
      scaffolds, MSC-mediated therapy and the expression of selective differentiating
      factors. The long-term behavior of MSCs associated with biomaterials and
      implanted in pathological joints remains to be investigated before clinical
      application in osteoarthritis or rheumatoid arthritis.

PMID- 15464370
TI  - Current strategies for cell delivery in cartilage and bone regeneration.
AB  - Several cell-based tissue-engineering therapies are emerging to regenerate
      damaged tissues. These strategies use autologous cells in combination with
      bioresorbable delivery materials. Major functions of a delivery scaffold are to
      provide initial mechanical stability, homogenous three-dimensional cell
      distribution, improved tissue differentiation, suitable handling and properties
      for delivery and fixation into patients. Delivery of cells can be achieved using
      injectable matrices, soft scaffolds, membranes, solid load-bearing scaffolds or
      immunoprotective macroencapsulation. Thus, to expand the clinical potential, next
      generation therapies will depend on smart delivery concepts that make use of the
      regenerative potential of stem cells, morphogenetic growth factors and biomimetic
      materials.

PMID- 15464371
TI  - Tissue engineering with muscle-derived stem cells.
AB  - Tissue engineering and cell therapy approaches aim to take advantage of the
      repopulating ability and plasticity of multipotent stem cells to regenerate lost
      or diseased tissue. Researchers continue to investigate stem cells in mature
      tissues and demonstrate the potential ability of organ-specific cells to
      differentiate into multiple lineages. One stem cell that displays such promise is
      the muscle-derived stem cell (MDSC). Data supporting the existence of MDSCs have
      emerged as part of investigations to improve myoblast cell transplantation for
      the treatment of muscular dystrophies. As these efforts continue, the potential
      for MDSC-based therapy for other musculoskeletal injuries, as well as for cardiac
      and smooth muscle injuries, is currently being explored.

PMID- 15464372
TI  - Tissue engineering of angiogenesis with autologous endothelial progenitor cells.
AB  - Adult bone marrow and peripheral blood contain small subsets of mononuclear cells
      that can be differentiated into endothelial-like cells in vitro. Experimental and
      clinical transplantation of such cell isolates--often referred to as endothelial
      stem/progenitor cells--into ischaemic or infarcted areas shows their
      incorporation into sites of new vessel growth along with improvement of regional
      blood flow. Emerging evidence suggests that these beneficial effects on vascular
      growth can be attributed to the paracrine activation of resident endothelial
      cells, rather than their integration into new endothelium. Autologous endothelial
      progenitor cells can also substitute for native vessel-derived endothelial cells
      in tissue-engineered vascular autografts.

PMID- 15464373
TI  - Cardiac tissue engineering: regeneration of the wounded heart.
AB  - New solutions are needed to regenerate hearts damaged by myocardial infarction,
      to overcome bad prognosis of patients with heart failure, and to address the
      shortage of heart donors. In the past few years, cardiac tissue engineering has
      emerged as a new and ambitious approach that combines knowledge from material
      chemistry with cell biology and medicine. In this short review, we present an
      overview on the most promising materials and cell-therapy strategies used in the
      past few years for the regeneration of the wounded heart.

PMID- 15464374
TI  - Islet- and stem-cell-based tissue engineering in diabetes.
AB  - New sources of insulin-producing cells are needed to overcome the limited
      availability of islet tissue for transplantation to diabetic patients. The
      engineering of murine or human transformed beta-cell lines and of non beta-cells
      has progressed slowly in recent years, while significant achievements have been
      claimed in the differentiation of insulin-producing cells from embryonic and
      adult stem cells. Some of the results have been questioned, however, and the
      generated cells lack many characteristics of differentiated beta-cells. A much
      better understanding of the processes that govern the expansion and
      differentiation of stem cells is needed.

PMID- 15464375
TI  - Biochemical engineering.

PMID- 15464376
TI  - Using functional genomics to improve productivity in the manufacture of
      industrial biochemicals.
AB  - Recent developments in the field of functional genomics have been used to
      increase productivity in the manufacture of industrial biochemicals. Technologies
      like transcriptomics and proteomics have profited from the increasing number of
      genome sequencing projects. Meanwhile functional genomics has evolved from
      several isolated technologies, such as DNA chip technology and proteomics, to
      combined approaches that can help us to understand why organisms produce a
      certain product. The combination of expression studies and kinetic studies, such
      as carbon flux determination or metabolite measurements, has significantly
      improved productivity in production processes.

PMID- 15464377
TI  - The use of enzyme mixtures for complex biosyntheses.
AB  - Biocatalysis is currently employed to produce known substances more economically
      and for the synthesis of new compounds. Increased production or novel product
      synthesis can be achieved through the use of mutant organisms, tailored enzymes
      or novel combinations of enzymes in reactors. These complex biosyntheses, once
      only in the realm of the biopharmaceutical industry, have now been embraced by
      the food and textile industries and are finding geochemical and environmental
      applications. New uses are dictating novel methods of manufacture that utilize
      knowledge of systems level biology. Increased understanding of the functional
      interaction of proteins and protein-protein networks is also altering the
      practice of in vitro biosynthesis.

PMID- 15464378
TI  - Production technologies for monoclonal antibodies and their fragments.
AB  - In recent years, monoclonal antibodies have emerged as an increasingly important
      class of human therapeutics. A variety of forms of antibodies, including
      fragments such as Fabs, Fab'2s and single-chain Fvs, are also being evaluated for
      a range of different purposes. A variety of expression systems and improvements
      within these systems have been developed to address these growing and diverse
      needs.

PMID- 15464379
TI  - Membrane bioreactors for the removal of anionic micropollutants from drinking
      water.
AB  - Biological treatment processes allow for the effective elimination of anionic
      micropollutants from drinking water. However, special technologies have to be
      implemented to eliminate the target pollutants without changing water quality,
      either by adding new pollutants or removing essential water components. Some
      innovative technologies that combine the use of membranes with the biological
      degradation of ionic micropollutants in order to minimize the secondary
      contamination of treated water include pressure-driven membrane bioreactors, gas
      transfer membrane bioreactors and ion exchange membrane bioreactors.

PMID- 15464380
TI  - Alternative bioseparation operations: life beyond packed-bed chromatography.
AB  - Chromatography is undoubtedly the workhorse of downstream processes, affording
      high resolution for bioseparations. At the same time, it has the notoriety of
      being the single largest cost center in downstream processing and of being a low
      throughput operation. Consequently, 'chromatography alternatives' are an
      attractive proposition, even if only a reduction in the extent of use of packed
      beds can be realized. This paper reviews the current state of unit operations
      posing as chromatography alternatives--including membrane filtration, aqueous two
      phase extraction, three-phase partitioning, precipitation, crystallization,
      monoliths and membrane chromatography--and their potential to do the unthinkable.

PMID- 15464381
TI  - Downstream processing of recombinant proteins from transgenic feedstock.
AB  - The search for inexpensive production systems capable of producing large
      quantities of recombinant protein has resulted in the development of new
      technology platforms based on transgenic plants and animals. Over the past
      decade, these transgenic systems have been used to produce several products and
      potential therapeutic proteins. Improvements continue to be made, not only in how
      the proteins are expressed but also in how the end products are obtained. As
      improvements in expression are realized, cost-saving measures will increasingly
      focus on downstream processing.

PMID- 15464382
TI  - Folding and refolding of proteins in chromatographic beds.
AB  - The correct folding of solubilized recombinant proteins is of key importance for
      their production in industry. On-column refolding of proteins is mainly achieved
      by three methods: size-exclusion chromatography, ion exchange chromatography and
      affinity chromatography using immobilized metal chelates. The principles of these
      methods were first laid down in the 1990s, but many recent improvements have been
      made to these processes including sophisticated changes to the mobile phase
      composition and the recycling of aggregates to improve yield. Advances have also
      been made in the use of immobilized metal affinity chromatography and by
      mimicking the natural folding process with artificial chaperones.

PMID- 15464383
TI  - Quorum sensing and bacterial cross-talk in biotechnology.
AB  - Only a decade ago, the secretion and perception of small signalling molecules
      that in turn are transduced to coordinate behaviour of a 'minimal unit' of
      microorganisms was termed quorum sensing by EP Greenberg and colleagues. Since
      then, an explosion (or exponential growth) in understanding and prevalence of
      quorum-sensing systems has ensued, with sightings ranging from virulence in human
      and plant pathogens to degradative capacity of activated sludge. Not
      surprisingly, regulatory mechanisms span traditional inducer/repressor motifs
      homologous to the lac operon to the recently discovered interfering RNAs. Further
      characterisation of signalling circuits, coupled with creative niche
      applications, suggest a wealth of opportunity for advancing commercial
      biotechnology.

PMID- 15464384
TI  - Metabolism of 3'-deoxy-3'-[F-18]fluorothymidine in proliferating A549 cells:
      validations for positron emission tomography.
AB  - 3'-Deoxy-3'-[F-18]fluorothymidine (FLT) is under clinical evaluation as a
      metabolic probe for imaging cell proliferation in vivo using positron emission
      tomography (PET). As part of our validation effort, we followed the short-term
      metabolism of FLT in exponentially growing tumor cells to demonstrate the enzyme
      activities within the DNA salvage pathway that influence retention of
      radioactivity. In A549 cells, thymidine kinase-1 (TK1) activity produced FLTMP,
      which dominated the labeled nucleotide pool. Subsequent nucleotide
      phosphorylations by thymidylate kinase (TMPK) and nucleotide diphosphate kinase
      (NDPK) led to FLTTP. After 1h, the cellular metabolic pool contained
      approximately 30% FLTTP. A putative deoxynucleotidase (dNT), which degrades FLTMP
      to FLT, provided the primary mechanism for tracer efflux from cells. In contrast,
      FLTTP was resistant to degradation and highly retained. The uptake and retention
      characteristics of FLT were also compared to those of thymidine, FMAU (2'-arabino
      fluoro-TdR) and FIAU (2'-arabino-fluoro-5-iodo-2'-dexoyuridine). Despite the fact
      that FLT lacks the 3'-hydroxy necessary for its incorporation into DNA it out
      performed both FMAU and FIAU in terms of uptake and retention.

PMID- 15464385
TI  - Synthesis and evaluation of a thymidine analog for positron emission tomography
      study of tumor DNA proliferation in vivo.
AB  - This study describes the synthesis, radiolabelling and biological evaluation of 5
      (2,4-difluoro-5-[18F]fluoromethyl-phenyl)-2-hydroxymethyl-tetrahydrofuran-3-ol,
      13. Radiolabelling was achieved by reaction of the tosylate 3 with K[18F] in the
      presence of Kryptofix 222. Good stability in saline and serum solutions at
      physiological temperatures in vitro was observed. A cell incorporation study of
      13 using SW1222 tumor cells showed a linear uptake, unfortunately, in vivo
      studies indicated that 13 was undergoing defluorination. Rapid defluorination of
      the radiotracer was confirmed by an in vitro stability study in blood plasma.
      Finally, a comparison between the DNA uptake of 13 and tritiated thymidine was
      performed in vitro to asses the potential utility of more stable analogs. These
      studies showed that 13 and its analogs are unsuitable as potential tracers to
      image DNA proliferation and highlighted the difficulty in predicting the in vivo
      stability of novel radiotracers.

PMID- 15464386
TI  - Synthesis and preclinical evaluation of the choline transport tracer deshydroxy
      [18F]fluorocholine ([18F]dOC).
AB  - 11C-labeled choline ([11C]CHO) and 18F-fluorinated choline analogues have been
      demonstrated to be valuable tracers for in vivo imaging of neoplasms by means of
      positron emission tomography (PET). The objective of the present study was to
      evaluate whether deshydroxy-[18F]fluorocholine, ([18F]dOC), a non-metabolizable
      [18F]fluorinated choline analogue, can serve as a surrogate for cholines that are
      able to be phosphorylated and thus allow PET-imaging solely by addressing the
      choline transport system. The specificity of uptake of [18F]dOC was compared with
      that of [11C]choline ([11C]CHO) in cultured rat pancreatic carcinoma and PC-3
      human prostate cancer cells in vitro. In addition, biodistribution of [18F]dOC
      and [11C]CHO was compared in AR42J- and PC-3 tumor bearing mice. The in vitro
      studies revealed that membrane transport of both compounds can be inhibited in a
      concentration dependent manner by similar concentrations of cold choline (IC50
      [18F]dOC= 11 microM; IC50 [11C]CHO=13 microM. In vitro studies with PC-3 and
      AR42J cells revealed that the internalized fraction of [18F]dOC after 5 min
      incubation time is comparable to that of [11C]CHO, whereas the uptake of [11C]CHO
      was superior after 20 min incubation time. As for [11C]CHO, kidney and liver were
      also the primary sites of uptake for [18F]dOC in vivo. Biodistribution data after
      simultaneous injection of both tracers into AR42J tumor bearing mice revealed
      slightly higher tumor uptake for [18F]dOC at 10 min post-injection, whereas
      [11C]CHO uptake was higher at later time points. In conclusion, [18F]dOC is taken
      up into AR42J rat pancreatic carcinoma and PC-3 human prostate cancer cells by a
      choline specific transport system. Similar transport rates of [18F]dOC and
      [11C]CHO result in comparable cellular uptake levels at early time points. In
      contrast to [18F]dOC, which is transported but not intracellularly trapped, the
      choline kinase substrate [11C]CHO is transported into tumor cells and retained.
      Thus, the signal obtained by imaging early after injection is mainly reflecting
      transport, whereas a valid quantification of choline kinase activity needs
      imaging at later time points. Further studies have to clarify whether
      quantification of the transport capacity or the choline kinase activity result in
      a better pathophysiological correlate and thus is the more useful process for
      tumor characterization.

PMID- 15464387
TI  - Radiolabeled choline as a proliferation marker: comparison with radiolabeled
      acetate.
AB  - [11C]Choline is a potential tracer to detect tumors, especially brain and
      prostate cancers. The metabolism of [11C]choline defines the accumulation pattern
      of [11C]choline in tumors depicted by positron emission tomography. Choline is a
      precursor of phosphatidylcholine that is a major constituent of membrane lipids.
      Membrane lipid synthesis as well as DNA synthesis is activated during cell
      proliferation. We investigated the relation between [14C]choline metabolism and
      proliferative activity using 10 tumor cell lines and fibroblasts. [14C]Choline
      uptake was higher in tumor cells than in fibroblasts and was correlated with the
      proliferative activity, though the sensitivity of [14C]choline uptake to
      proliferative activity was less than that of [1-14C]acetate. [14C]Phosphocholine
      produced from [14C]choline by phosphorylation mainly contributed to this
      accumulation. [11C]Choline can be used for the evaluation of tumor proliferation
      through estimating choline kinase activity.

PMID- 15464388
TI  - Effects of 2-methoxyestradiol on proliferation, apoptosis and PET-tracer uptake
      in human prostate cancer cell aggregates.
AB  - The purpose of this study was to investigate the potential use of PET in vivo to
      record cytotoxic effects of 2-methoxyestradiol (2-ME), an endogenous metabolite
      of 17beta-estradiol. The anti-proliferative and pro-apoptotic effects of 2-ME on
      human prostate cancer cell (PC3) aggregates in vitro, were correlated with the
      uptake of fluoro-deoxy-D-glucose, FMAU and choline labelled with 18F, 11C, or 3H.
      2-ME clearly reduced growth of PC3 aggregates and induced apoptosis in a dose
      dependent manner. However, the uptake of the putative proliferation markers 11C
      FMAU or 3H-choline failed to record the growth inhibitory effects of 2-ME on PC3
      cell aggregates. The uptake of 18F-FDG was used as a marker for effects on
      cellular metabolism and also failed to show any dose-dependent effects in PC3
      aggregates. The use of these PET-tracers in vivo is therefore not recommended in
      order to evaluate the cytotoxic effects of 2-ME on human prostate cancer cells.

PMID- 15464390
TI  - Impact of reversible trapping of tracer and the presence of blood metabolites on
      measurements of myocardial glucose utilization performed by PET and 18F
      fluorodeoxyglucose using the Patlak method.
AB  - In this study we demonstrated that significant egress of FDG from myocardium
      occurs within the first hour after tracer injection leading to nonlinear Patlak
      plots. There are also significant amounts of acidic FDG metabolites present in
      the blood. However, the impact of these metabolites on the estimates of
      myocardial glucose utilization (MGU) is negligible. Although further studies will
      be required to elucidate the reason for the egress of tracer from myocardium, not
      accounting for it will result in erroneous estimates of MGU.

PMID- 15464389
TI  - Influence of ceftriaxone treatment on FDG uptake--an in vivo [18F]
      fluorodeoxyglucose imaging study in soft tissue infections in rats.
AB  - Our aim was to determine the influence of antibiotic treatment using ceftriaxone
      on [18F]-fluorodeoxyglucose (FDG) uptake in experimental soft tissue infections.
      PET scans were performed in two groups (treated n=4; non-treated n=4) at days 3,
      5, and 6 after inoculation of the infection. Additional autoradiography was
      performed in four animals at day 7 and in three animals at day 11. The difference
      of FDG uptake on day 5 (after three days of antibiotic treatment) between both
      groups proved to be significant (df=6; T=2.52; p=0.045). FDG uptake determined at
      the other days did not reveal significant difference between the two groups. It
      seems to be possible that the effect of antibiotic treatment on FDG uptake is
      less evident than reported for therapy monitoring of cancer treatment. The change
      of FDG uptake over time in treated and untreated infections is complex and
      further in vivo experiments have to be initiated to investigate the potential
      value of clinical FDG PET in therapy monitoring of infection.

PMID- 15464391
TI  - 99mTc-labeled mannosyl-neoglycoalbumin for sentinel lymph node identification.
AB  - 99mTc-labeled mannosyl-neoglycoalbumin (NMA) was prepared and evaluated as a
      radiopharmaceutical for sentinel lymph node (SLN) identification, since 99mTc
      labeled human serum albumin (HSA) rapidly cleared from injection sites. NMA was
      conjugated with 6-hydrazinopyridine-3-carboxylic acid (HYNIC) and reacted with
      [99mTc](tricine)2 to prepare [99mTc](HYNIC-NMA)(tricine)2. After subcutaneous
      injection of [99mTc](HYNIC-NMA)(tricine)2 from murine foot pad, radioactivity
      levels in the popliteal and lumbar lymph nodes, the injection site and other
      tissues were compared with those of [99mTc](HYNIC-HSA)(tricine)2 and 99mTc
      labeled colloidal rhenium sulfate ([99mTc]colloid). [99mTc](HYNIC-NMA)(tricine)2
      demonstrated significantly higher radioactivity levels in the popliteal lymph
      node, the SLN in this model, than did [99mTc](HYNIC-HSA)(tricine)2 and
      [99mTc]colloid at 0.5, 1, and 6 h post-injection. [99mTc](HYNIC-NMA)(tricine)2
      showed a dose-dependent decrease in the popliteal accumulation while the
      radioactivity levels in the blood, liver and spleen increased with an increase in
      the molar dose of NMA. [99mTc]colloid registered a decrease in the radioactivity
      levels in the popliteal lymph node, blood, liver, and spleen with dilution.
      However, the radioactivity levels at the injection site increased with dilution
      of [99mTc] colloid. Both [99mTc](HYNIC-NMA)(tricine)2 and [99mTc](HYNIC
      HSA)(tricine)2 showed the radioactivity levels at the injection site similar each
      other. These findings indicated that an addition of a macrophage binding function
      to 99mTc-labeled HSA provided high and selective accumulation of the
      radioactivity in the SLN without affecting the elimination rate from the
      injection site. Such characteristics render [99mTc](HYNIC-NMA)(tricine)2
      attractive as a radiopharmaceutical for SLN identification. This study also
      demonstrated that the number of non-radiolabeled colloidal particles and the
      molar dose of mannosylated compounds play a crucial role in the SLN accumulation.

PMID- 15464392
TI  - 227Th-EDTMP: a potential therapeutic agent for bone metastasis.
AB  - The biodistribution of 227Th-EDTMP and retention of its daughter nuclide 223Ra
      were examined. 227Th-EDTMP was found to show high uptake and long-term retention
      in bone. The clearance of 227Th-EDTMP from blood and soft tissues was rapid and
      the femur-to-tissue uptake ratios reached more than 100 within 30 min for all
      tissues except the kidney. Seven and 14 days after injection of 227Th-EDTMP, the
      retention index of 223Ra in bone showed high values, and the differences between
      these time points were not significant. Therefore, 227Th-EDTMP is a potential
      radiotherapeutic agent for bone metastasis.

PMID- 15464393
TI  - Evaluation of an internalizing monoclonal antibody labeled using N-succinimidyl 3
      [131I]iodo-4-phosphonomethylbenzoate ([131I]SIPMB), a negatively charged
      substituent bearing acylation agent.
AB  - Monoclonal antibodies such as L8A4, reactive with the epidermal growth factor
      receptor variant III, internalize after receptor binding resulting in proteolytic
      degradation by lysosomes. Labeling internalizing mAbs requires the use of
      methodologies that result in the trapping of labeled catabolites in tumor cells
      after intracellular processing. Herein we have investigated the potential utility
      of N-succinimidyl-3-[131I]iodo-4-phosphonomethylbenzoate ([131I]SIPMB), an
      acylation agent that couples the corresponding negatively charged acid
      [131I]IPMBA to the protein, for this purpose. Biodistribution studies
      demonstrated that [131I]IPMBA cleared rapidly from normal tissues and exhibited
      thyroid levels < or =0.1% injected dose, consistent with a low degree of
      dehalogenation. Biodistribution experiments in athymic mice bearing subcutaneous
      D-256 human glioma xenografts were performed to compare L8A4 labeled using
      [131I]SIPMB to L8A4 labeled with 125I using both the analogous positively charged
      acylation agent N-succinimidyl-4-guanidinomethyl-3-[125I]iodobenzoate
      ([125I]SGMIB) and Iodogen. Tumor uptake of [131I]SIPMB-L8A4 (41.9+/-3.5% ID/g)
      was nearly threefold that of L8A4 labeled using Iodogen (14.0+/-1.1% ID/g) after
      2 days, and tumor to tissue ratios remained uniformly high throughout with
      [131I]SIPMB-L8A4. Thyroid uptake increased for the Iodogen labeled mAb (3.55+/
      0.36 %ID at 5 days) whereas that of [131I]SIPMB labeled mAb remained low (0.21+/
      0.04% ID at 5 days). In the second biodistribution, L8A4 labeled using
      [131I]SIPMB and [125I]SGMIB showed no difference in normal tissue uptake and had
      nearly identical tumor uptake ([131I]SIPMB, 41.8+/-14.2% ID/g; [125I]SGMIB,
      41.6+/-15.8% ID/g, at 4 days). These results suggest that [131I]SIPMB may be a
      viable acylation agent for the radioiodination of internalizing mAbs.

PMID- 15464394
TI  - Backbone metal cyclization: novel 99mTc labeled GnRH analog as potential SPECT
      molecular imaging agent in cancer.
AB  - Gonadotropin-releasing hormone (GnRH) is a decapeptide secreted to the pituitary
      where it binds to specific receptors on the gonadotropes to regulate gonadotropic
      hormones (luteinizing hormone (LH) and follicle-stimulating hormone (FSH))
      synthesis and secretion. Specific GnRH receptors are overexpressed in breast,
      prostatic, ovarian, and other tumors. The aim of this study was to synthesize a
      cyclic GnRH analog with high affinity to GnRH receptors that can be radiolabeled
      with 99mTc. A precyclic GnRH analog, [Cys-Gly]1[D-Ala]6[N(alpha)(eta-Cys-amino
      hexyl)]10GnRH (Gn-2), containing two hemi-chelator groups was synthesized. It was
      cyclized applying the recently reported backbone metal cyclization (BMC)
      approach, to obtain cyclo(Re(O)1-10)[Cys-Gly]1[D-Ala]6[N(alpha)(eta-Cys-amino
      hexyl)]10GnRH (cyclo[Re(O)-Gn-2]). For comparative evaluations, Gn-2 was oxidized
      on-resin to yield cyclo(S-S,1-10)[Cys-Gly]1[D-Ala]6[N(alpha)(eta-Cys-amino
      hexyl)]10GnRH, (cyclo[S-S-Gn-2]). The binding affinity of cyclo[Re(O)-Gn-2] to
      rat pituitary membranes showed IC50 of 50 nM, compared to IC50 = 10 nM in the
      native GnRH. Cyclo(99mTc(O)1-10)[Cys-Gly]1[D-Ala]6[N(alpha)(eta-Cys-amino
      hexyl)]10GnRH (cyclo[99mTc(O)-Gn-2]) was synthesized from Gn-2 and showed similar
      chromatographic behavior to its rhenium surrogate.

PMID- 15464395
TI  - A facile no-carrier-added radioiodination procedure suitable for radiolabeling
      kits.
AB  - A simple, straightforward radioiodination procedure has been developed that is
      ideal for use in the construction of radioiodination kits. Isolation of no
      carrier-added radioiodinated products from the ionic precursors is readily
      achieved using simple Sep-Pak filtrations.

PMID- 15464396
TI  - In vivo evaluation of [11C]N-(2-chloro-5-thiomethylphenyl)-N'-(3-methoxy-phenyl)
      N'-methylguanidine ([11C]GMOM) as a potential PET radiotracer for the PCP/NMDA
      receptor.
AB  - The development of imaging methods to measure changes in NMDA ion channel
      activation would provide a powerful means to probe the mechanisms of drugs and
      device based treatments (e.g., ECT) thought to alter glutamate neurotransmission.
      To provide a potential NMDA/PCP receptor PET tracer, we synthesized the
      radioligand [11C]GMOM (ki = 5.2 +/-0.3 nM; log P = 2.34) and evaluated this
      ligand in vivo in awake male rats and isoflurane anesthetized baboons. In rats,
      the regional brain uptake of [11C]GMOM ranged from 0.75+/-0.13% ID/g in the
      medulla and pons to 1.15+/-0.17% ID/g in the occipital cortex. MK801 (1 mg/kg
      i.v.) significantly reduced (24-28%) [11C]GMOM uptake in all regions. D-serine
      (10 mg/kg i.v.) increased [11C]GMOM %ID/g values in all regions (10-24%) reaching
      significance in the frontal cortex and cerebellum only. The NR2B ligand RO 25
      6981 (10 mg/kg i.v.) reduced [11C]GMOM uptake significantly (24-38%) in all
      regions except for the cerebellum and striatum. Blood activity was 0.11+/-0.03
      %ID/g in the controls group and did not vary significantly across groups. PET
      imaging in isoflurane-anesthetized baboons with high specific activity [11C]GMOM
      provided fairly uniform regional brain distribution volume (VT) values (12.8-17.1
      ml g(-1)). MK801 (0.5 mg/kg, i.v., n = 1, and 1.0 mg/kg, i.v., n = 1) did not
      significantly alter regional VT values, indicating a lack of saturable binding.
      However, the potential confounding effects associated with ketamine induction of
      anesthesia along with isoflurane maintenance must be considered because both
      agents are known to reduce NMDA ion channel activation. Future and carefully
      designed studies, presumably utilizing an optimized NMDA/PCP site tracer, will be
      carried out to further explore these hypotheses. We conclude that, even though
      [11C]GMOM is not an optimized PCP site radiotracer, its binding is altered in
      vivo in awake rats as expected by modulation of NMDA ion channel activity by
      MK801, D-serine or RO 25-6981. The development of higher affinity NMDA/PCP site
      radioligands is in progress.

PMID- 15464397
TI  - Potential of [11C]TMSX for the evaluation of adenosine A2A receptors in the
      skeletal muscle by positron emission tomography.
AB  - We examined the potential of [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7
      trimethylxanthine ([11C]TMSX) for the assessment of adenosine A2A receptors in
      muscle. In rodents, specific binding of [11C]TMSX was observed in muscle and
      heart by blockade with A2A-selective CSC and non-selective theophylline, but not
      with A1-selective DPCPX. Swimming exercise fluctuated radioligand-receptor
      binding in these tissues. In a PET study of two subjects, theophylline-infusion
      slightly deceased the distribution volume of [11C]TMSX in the heart (20%
      reduction) and muscle (10% reduction), which suggested the specific binding.

PMID- 15464398
TI  - Facile synthesis and initial PET imaging of novel potential heart
      acetylcholinesterase imaging agents [11C]pyridostigmine and its analogs.
AB  - A series of 11C-labeled analogs of the acetylcholinesterase (AChE) inhibitor
      pyridostigmine have been synthesized for evaluation as new potential positron
      emission tomography (PET) imaging agents for heart AChE. The appropriate
      precursors for radiolabeling were slightly modified from commercial reagents. The
      new tracers [11C]pyridostigmine (1), [11C]para-pyridostigmine (2) and [11C]ortho
      pyridostigmine (3) were prepared by N-[11C]methylation of the precursors using
      [11C]methyl triflate. Pure target compounds were isolated by a solid-phase
      extraction (SPE) purification procedure with 60-85% radiochemical yields (decay
      corrected to end of bombardment), and a synthesis time of 10-15 min. The initial
      PET dynamic studies of compounds (1-3) in rat heart showed rapid heart uptake and
      blood pool clearance to give high quality heart images. These results suggest the
      new tracers delineate the heart very clearly and could be potential heart AChE
      imaging agents.

PMID- 15464399
TI  - In vivo measurement of circulating leucocyte activation in patients following
      cardiopulmonary bypass.
AB  - We have developed a simple technique to measure in vivo activation of circulating
      leucocytes and assessed it in 6 patients undergoing cardiopulmonary bypass (CPB).
      Arterial, mixed venous, and jugular bulb blood samples were taken following i.v.
      [18F]FDG, before and after CPB. [18F]FDG uptake in leucocytes was measured by
      phosphor imaging of spun blood-filled capillary tubes. Leucocyte radioactivity
      was quantified ([(leucocytes-plasma)/plasma radioactivity] and normalised to
      leucocyte counts. [18F]FDG uptake (mean+/-SEM)) before CPB was undetectable,
      being -0.014+/-0.007, -0.011+/-0.003, -0.012+/-0.006, -0.010+/-0.005, whereas
      increased uptake was demonstrated following CPB, 0.006+/-0.006, 0.009+/-0.005,
      0.021+/-0.005, 0.034+/-0.006, at 20, 40, 60, and 80 min, respectively. There was
      no significant difference in activation between sampling sites before or after
      CPB. This method gives a sensitive index of activation of circulating leucocytes
      in whole blood, enabling investigation of activation of circulating white cells
      without the influence of sample handling or the requirement for time-consuming
      cell separation procedures.

PMID- 15464401
TI  - Multiple memory systems.

PMID- 15464402
TI  - Memory systems of the brain: a brief history and current perspective.
AB  - The idea that memory is composed of distinct systems has a long history but
      became a topic of experimental inquiry only after the middle of the 20th century.
      Beginning about 1980, evidence from normal subjects, amnesic patients, and
      experimental animals converged on the view that a fundamental distinction could
      be drawn between a kind of memory that is accessible to conscious recollection
      and another kind that is not. Subsequent work shifted thinking beyond dichotomies
      to a view, grounded in biology, that memory is composed of multiple separate
      systems supported, for example, by the hippocampus and related structures, the
      amygdala, the neostriatum, and the cerebellum. This article traces the
      development of these ideas and provides a current perspective on how these brain
      systems operate to support behavior.

PMID- 15464403
TI  - What, if anything, is the medial temporal lobe, and how can the amygdala be part
      of it if there is no such thing?
AB  - Should the medial temporal lobe (MTL) of primates--which includes allocortical
      structures such as the hippocampus, neocortical structures such as the
      parahippocampal cortex, and nuclear structures such as the basolateral amygdala-
      be considered a single "thing"? According to the prevailing view, here termed the
      reification theory, the answer is yes. According to this theory, the MTL
      functions as an amalgamated entity that provides the neuronal mechanisms for
      declarative memory; the greater the damage to the MTL or any of its components,
      the greater the deleterious effects on declarative memory. A countervailing view,
      here called the balkanization theory, holds that the various components of the
      MTL process and store different kinds of information. According to this theory,
      damage to each part of the MTL causes a unique set of behavioral deficits-some
      involving memory, others involving perception, and yet others involving response
      selection. The empirical neuropsychological evidence favors the balkanization
      theory, as do some new concepts in theoretical neuroanatomy.

PMID- 15464404
TI  - An analysis of independence and interactions of brain substrates that subserve
      multiple attributes, memory systems, and underlying processes.
AB  - It is proposed that memory is organized into event-based, knowledge-based, and
      rule-based memory systems. Furthermore, each system is composed of the same set
      of multiple attributes and characterized by a set of process oriented operating
      characteristics that are mapped onto multiple neural regions and interconnected
      neural circuits. Based on this theoretical model of memory, it is possible to
      investigate the independence and interaction among brain regions between any two
      systems for any of the proposed attributes or processes. This applies also to the
      investigation of independence and interactions between any two attributes within
      a system and between processes associated with a system for any of the proposed
      attributes. In this article, research evidence is presented to suggest that there
      are both dissociations and interactions between the hippocampus and caudate
      nucleus in mediating spatial and response attributes within the event-based
      memory system, between the hippocampus and the parietal cortex in subserving the
      spatial attribute within the event-based and knowledge-based memory systems, and
      between the hippocampus and the prefrontal cortex in subserving the spatial
      attribute within the event-based and rule-based memory systems.

PMID- 15464405
TI  - The role of stimulus ambiguity and movement in spatial navigation: a multiple
      memory systems analysis of location discrimination.
AB  - This paper reviews recent findings about how rats navigate by learning to
      discriminate among locations. The assumption underlying the experiments and their
      interpretation is that the information required to do this is learned by three
      independent, parallel memory systems. One system processes cognitive information
      (or "knowledge"), a second system processes reinforced stimulus-response
      associations and a third processes Pavlovian conditioned responses in the form of
      stimulus-affect associations. The information stored in each system produces
      behavior that, in some cases, results in a location discrimination. The present
      experiments focus on three factors that influence what each system learns and
      whether the resulting memory produces behavior that results in a location
      discrimination. One factor is whether the locations to be discriminated can be
      identified by unique, unambiguous stimuli or whether they are ambiguously
      associated with the same stimuli. The second factor is whether the stimuli are
      observed passively or whether the rats move among them, voluntarily or
      involuntarily. The third factor is whether or not the rats perform specific
      reinforced responses in the presence of the stimuli. Instances of co-operative
      behavioral outputs from memory systems that facilitate location discriminations
      and of competitive outputs that impede discriminations are described.

PMID- 15464406
TI  - Coordination of multiple memory systems.
AB  - On the basis of lesions of different brain areas, several neural systems appear
      to be important for processing information regarding different types of learning
      and memory. This paper examines the development of pharmacological and
      neurochemical approaches to multiple memory systems from past studies of
      modulation of memory formation. The findings suggest that peripheral
      neuroendocrine mechanisms that regulate memory processing may target their
      actions toward those neural systems most engaged in the processing of learning
      and memory. In addition, measurements of acetylcholine release in different
      memory systems reveals extensive interactions between memory systems, some
      cooperative and some competitive. These results imply that many neural systems,
      often characterized as relatively independent, may in fact interact extensively,
      blurring the dependencies of different memory tasks on specific neural systems.

PMID- 15464407
TI  - Amygdala and "emotional" modulation of the relative use of multiple memory
      systems.
AB  - The basolateral amygdala modulates the cognitive and habit memory processes
      mediated by the hippocampus and caudate nucleus, respectively. The present
      experiments used a plus-maze task that can be acquired using either hippocampus
      dependent "place" learning or caudate-dependent "response" learning to examine
      whether peripheral or intra-basolateral amygdala injection of anxiogenic drugs
      would bias rats towards the use of a particular memory system. In Experiment 1,
      adult male Long-Evans rats were trained to swim from the same start point to an
      escape platform located in a consistent goal arm, and received pre-training
      peripheral injections of the alpha(2)-adrenoceptor antagonists yohimbine (2.5 or
      5.0 mg/kg), RS 79948-197 (0.05, 0.1, or 0.2 mg/kg), or vehicle. On a drug-free
      probe trial from a novel start point administered 24h following acquisition,
      vehicle treated rats predominantly displayed hippocampus-dependent place
      learning, whereas rats previously treated with yohimbine (2.5, 5.0 mg/kg) or RS
      79948-197 (0.1 mg/kg) predominantly displayed caudate-dependent response
      learning. In Experiment 2, rats receiving pre-training intra-basolateral amygdala
      infusions of RS 79948-197 (0.1 microg/0.5 microl) also predominantly displayed
      response learning on a drug-free probe trial. The findings indicate (1)
      peripheral injections of anxiogenic drugs can influence the relative use of
      multiple memory systems in a manner that favors caudate-dependent habit learning
      over hippocampus-dependent cognitive learning, and (2) intra-basolateral amygdala
      infusion of anxiogenic drugs is sufficient to produce this modulatory influence
      of emotional state on the use of multiple memory systems.

PMID- 15464408
TI  - Hippocampus, cortex, and basal ganglia: insights from computational models of
      complementary learning systems.
AB  - We present a framework for understanding how the hippocampus, neocortex, and
      basal ganglia work together to support cognitive and behavioral function in the
      mammalian brain. This framework is based on computational tradeoffs that arise in
      neural network models, where achieving one type of learning function requires
      very different parameters from those necessary to achieve another form of
      learning. For example, we dissociate the hippocampus from cortex with respect to
      general levels of activity, learning rate, and level of overlap between
      activation patterns. Similarly, the frontal cortex and associated basal ganglia
      system have important neural specializations not required of the posterior cortex
      system. Taken together, this overall cognitive architecture, which has been
      implemented in functioning computational models, provides a rich and often subtle
      means of explaining a wide range of behavioral and cognitive neuroscience data.
      Here, we summarize recent results in the domains of recognition memory,
      contextual fear conditioning, effects of basal ganglia lesions on stimulus
      response and place learning, and flexible responding.

PMID- 15464409
TI  - Learning-induced activation of transcription factors among multiple memory
      systems.
AB  - Experimental evidence for multiple memory systems grew initially from reports
      that integrity of the medial temporal lobes is necessary for some, but not all,
      types of memory formation. A primary inference from many studies of multiple
      memory systems is that they operate independently during encoding, storage, and
      retrieval of information. An accumulation of recent evidence, however, suggests
      that multiple memory systems may interact under some conditions. At the cellular
      level of analysis, it is accepted widely that protein synthesis is necessary for
      the formation of long-term memory and recent efforts have focused on the
      mechanisms by which learning-induced gene transcription and translation are
      regulated. The present review examines learning-induced activation of
      transcription factors among multiple memory systems. The results indicate that
      studies of transcriptional regulation, in conjunction with other experimental
      approaches, can provide complementary lines of evidence to further understanding
      of the extent to which multiple memory systems are independent or interactive.

PMID- 15464410
TI  - Parallel processing across neural systems: implications for a multiple memory
      system hypothesis.
AB  - A common conceptualization of the organization of memory systems in brain is that
      different types of memory are mediated by distinct neural systems. Strong support
      for this view comes from studies that show double (or triple) dissociations
      between spatial, response, and emotional memories following selective lesions of
      hippocampus, striatum, and the amygdala. Here, we examine the extent to which
      hippocampal and striatal neural activity patterns support the multiple memory
      systems view. A comparison is made between hippocampal and striatal neural
      correlates with behavior during asymptotic performance of spatial and response
      maze tasks. Location- (or place), movement, and reward-specific firing patterns
      were found in both structures regardless of the task demands. Many, but not all,
      place fields of hippocampal and striatal neurons were similarly affected by
      changes in the visual and reward context regardless of the cognitive demands.
      Also, many, but not all, hippocampal and striatal movement-sensitive neurons
      showed significant changes in their behavioral correlates after a change in
      visual context, irrespective of cognitive strategy. Similar partial
      reorganization was observed following manipulations of the reward condition for
      cells recorded from both structures, again regardless of task. Assuming that
      representations that persist across context changes reflect learned information,
      we make the following conclusions. First, the consistent pattern of partial
      reorganization supports a view that the analysis of spatial, response, and
      reinforcement information is accomplished via an error-driven, or match-mismatch,
      algorithm across neural systems. Second, task-relevant processing occurs
      continuously within hippocampus and striatum regardless of the cognitive demands
      of the task. Third, given the high degree of parallel processing across allegedly
      different memory systems, we propose that different neural systems may
      effectively compete for control of a behavioral expression system. The strength
      of the influence of any one neural system on behavioral output is likely
      modulated by factors such as motivation, experience, or hormone status.

PMID- 15464411
TI  - The use of acute ethanol administration as a tool to investigate multiple memory
      systems.
AB  - The discovery of multiple memory systems supported by discrete brain regions has
      been one of the most important advances in behavioral neuroscience. A wealth of
      studies have investigated the role of the hippocampus and related structures in
      supporting various types of memory classifications. While the exact
      classification that best describes hippocampal function is often debated, a
      specific subset of cognitive function that is focused on the use of spatial
      information to form hippocampal cognitive maps has received extensive
      investigation. These studies frequently employ a variety of experimental
      manipulations including brain lesions, temporary neural blockade due to cooling
      or discrete injections of specific drugs. While these studies have provided
      important insights into the function of the hippocampus, they are limited due to
      the invasive nature of the manipulation. Ethanol is a drug that is easily
      administered in a non-invasive fashion, is rapidly absorbed and produces effects
      only in specific brain regions. The hippocampus is one brain region affected by
      acute ethanol administration. The following review summarizes research from the
      last 20 years investigating the effects of acute ethanol administration on one
      specific type of hippocampal cognitive function, namely spatial memory. It is
      proposed that among its many effects, one specific action of acute ethanol
      administration is to produce similar cognitive and neurophysiological effects as
      lesions of the hippocampus. Based on these similarities and the ease of its use,
      it is concluded that acute ethanol administration is a valuable tool in studying
      hippocampal function and multiple memory systems.

PMID- 15464412
TI  - Role of estrogen in balancing contributions from multiple memory systems.
AB  - In addition to modulating memory per se, estrogen alters the learning strategy
      used to solve a task, thereby regulating the quality of information processed by
      the brain. This review discusses estrogen's actions on cognition within a memory
      systems framework, highlighting our work with a variety of paradigms showing that
      learning strategy is sensitive to estrogen even when learning rate is not.
      Specifically, high levels of gonadal steroids, in particular, elevations in
      estrogen, bias female rats toward using hippocampal-sensitive approaches while
      low levels of gonadal steroids promote the use of non-hippocampal sensitive
      strategies. In light of findings from a variety of approaches involving the
      hippocampus in allocentric and the striatum in egocentric response patterns, it
      is likely that estrogen alters the relative participation of these, and most
      undoubtedly other, neural systems during cognition. Changes in neuromodulators
      such as acetylcholine that regulate other processes such as inhibitory tone and
      excitability reflect one mechanism by which estrogen may orchestrate learning and
      memory.

PMID- 15464413
TI  - How do memory systems interact? Evidence from human classification learning.
AB  - Studies of human classification learning using functional neuroimaging have
      suggested that basal ganglia and medial temporal lobe memory systems may interact
      during learning. We review these results and outline a set of possible mechanisms
      for such interactions. Effective connectivity analyses suggest that interaction
      between basal ganglia and medial temporal lobe are mediated by prefrontal cortex
      rather than by direct connectivity between regions. A review of possible
      neurobiological mechanisms suggests that interactions may be driven by
      neuromodulatory systems in addition to mediation by interaction of inputs to
      prefrontal cortical neurons. These results suggest that memory system
      interactions may reflect multiple mechanisms that combine to optimize behavior
      based on experience.

PMID- 15464414
TI  - Multiple memory systems: the power of interactions.
AB  - Two relatively simple theories of brain function will be used to demonstrate the
      explanatory power of multiple memory systems in your brain interacting
      cooperatively or competitively to directly or indirectly influence cognition and
      behaviour. The view put forth in this mini-review is that interactions between
      memory systems produce normal and abnormal manifestations of behaviour, and by
      logical extension, an understanding of these complex interactions holds the key
      to understanding debilitating brain and psychiatric disorders.

PMID- 15464415
TI  - Gaucher disease: complexity in a "simple" disorder.
AB  - Gaucher disease, the recessively inherited deficiency of the enzyme
      glucocerebrosidase and the most common sphingolipidosis, has both non
      neurological and neuronopathic forms and a continuum of diverse clinical
      manifestations. Studies of genotype-phenotype correlations reveal significant
      genotypic heterogeneity among clinically similar patients, and vastly different
      phenotypes among patients with the same mutations. The region surrounding the
      glucocerebrosidase gene (GBA) on chromosome 1q is particularly gene-rich, with a
      highly homologous pseudogene sequence 16 kb downstream. Recombination events
      within the GBA locus contribute to the etiology of some mutations in Gaucher
      disease. Studies of patients with Gaucher disease and atypical manifestations,
      including parkinsonism, myoclonic epilepsy, cardiac involvement and collodion
      skin, seek to define other genetic or environmental factors contributing to the
      phenotypes. Recent reports demonstrating an association between Gaucher disease
      and parkinsonism provide an example of heterozygosity for a Mendelian disorder
      acting as a risk factor for a complex disease. There are rare patients with
      Gaucher disease and differing genotypes who develop early onset, treatment
      refractory parkinsonism. Neuropathology in a group of these patients showed alpha
      synuclein-reactive Lewy bodies in brain regions specifically associated with
      Gaucher disease. Family studies of these probands suggested that the incidence of
      parkinsonism might be more frequent in obligate heterozygotes. In a complementary
      finding, the examination of GBA in autopsy samples from individuals with sporadic
      Parkinson disease identified alterations in the GBA sequence in 14% of the
      cohort. These studies provide evidence that altered glucocerebrosidase may
      contribute to a vulnerability to parkinsonism. Moreover, this research
      demonstrates how insights from rare, single gene disorders like Gaucher disease
      can provide a window into the etiology of more common, multifactorial genetic
      diseases.

PMID- 15464416
TI  - Peroxisomes, lipid metabolism, and peroxisomal disorders.
AB  - Peroxisomes catalyse a large variety of different cellular functions of which
      most have to do with lipid metabolism. This paper deals with the role of
      peroxisomes in three key pathways of lipid metabolism, including: (1)
      etherphospholipid biosynthesis, (2) fatty acid beta-oxidation, and (3) fatty acid
      alpha-oxidation. Apart from a brief description of the peroxisomal enzymes
      involved in each of these pathways, the interaction between peroxisomes and other
      subcellular organelles, notably microsomes and peroxisomes, will be discussed.
      Finally, the current state of knowledge with respect to the different disorders
      of peroxisomal lipid metabolism will be described.

PMID- 15464417
TI  - Propionic acidemia: mutation update and functional and structural effects of the
      variant alleles.
AB  - Mutations in the PCCA or PCCB genes, encoding both subunits of propionyl-CoA
      carboxylase, result in propionic acidemia, a life-threatening inborn error of
      metabolism with autosomal recessive inheritance. To date, 41 mutations in the
      PCCA gene and 54 in the PCCB gene have been reported, most of them single base
      substitutions causing amino acid replacements, and a variety of small insertions
      and deletions and splicing defects. A greater heterogeneity is observed in the
      PCCA gene, specially in Caucasians, with no prevalent mutations, while in the
      Japanese population three mutations account for more than half of the alleles
      studied. For the PCCB gene a limited number of mutations is responsible for the
      majority of the alleles characterized in both Caucasian and Oriental populations.
      These two populations show a different mutational spectrum, only sharing some
      involving CpG dinucleotides probably as recurrent mutational events. Functional
      characterization of the mutant missense alleles has been accomplished using
      different prokaryotic and eukaryotic systems, and the structural consequences
      have been analyzed in the available crystal models. For the PCCA gene, the main
      molecular effect of the expressed mutations is related to protein instability,
      except two mutations in the active site predictably affecting ATP binding. In the
      PCCB gene the majority of the analyzed mutations are predicted to alter the
      active site conformation resulting in diminished activity. A few carboxy-terminal
      PCCB mutations affect the interaction between subunits and the assembly with PCCA
      to form a functional PCC oligomer. The amount of normal transcripts resulting
      from some PCCA and PCCB splicing mutations has also been analyzed. Overall, the
      data generated from the expression analysis reveal potential genotype-phenotype
      correlations for this clinically heterogeneous disorder.

PMID- 15464418
TI  - Genetic heterogeneity in primary hyperoxaluria type 1: impact on diagnosis.
AB  - Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disease
      characterized by progressive kidney failure due to renal deposition of calcium
      oxalate. The disease is caused by a deficiency of alanine:glyoxylate
      aminotransferase (AGT) which catalyzes the conversion of glyoxylate to glycine.
      When AGT is absent, glyoxylate is converted to oxalate which forms insoluble
      calcium salts that accumulate in the kidney and other organs. In the most common
      phenotype there is a unique phenomenon wherein AGT is mis-targeted to the
      mitochondria instead of the peroxisomes. The diagnosis of PH1 is complicated by
      heterogeneity of clinical presentation, course of the disease, biochemical
      markers, AGT enzymatic activity and genotype. More than 50 mutations and
      polymorphisms have been reported in the AGT gene; three common mutations
      accounting for almost 50% of PH1 alleles. The mutations are of all types, with
      missense making up the largest fraction. There are some mutations with apparent
      ethnic associations and at least one that appears to be pan-ethnic. Although
      correlations can in some cases be made between biochemical phenotype and
      genotype, correlation with clinical phenotype is complicated by the involvement
      of other genetic and non-genetic factors that affect disease severity. A number
      of polymorphisms have been described in the AGT gene some of which cause missense
      changes and, in some cases, alter enzyme activity. As DNA testing becomes more
      commonly used for diagnosis it is important to correlate observed sequence
      changes with previously documented changes as an aid to assessing their potential
      significance.

PMID- 15464419
TI  - A renaissance of "biochemical genetics"? SNPs, haplotypes, function, and complex
      diseases.
AB  - We have made remarkable progress in understanding the molecular bases of many
      Mendelian diseases over the past 2-3 decades. The current interest in discovering
      the molecular basis of complex diseases uses either linkage or candidate gene
      approaches. The latter often uses case/control (or case/cohort) study designs. We
      believe it is critically important to have a thorough understanding of SNP
      (single nucleotide) and haplotype function in such endeavors. Functionally
      neutral SNPs and haplotypes are probably best suited for linkage studies (far
      away from the locus of interest). Functionally relevant SNPs and haplotypes seem
      best suited for candidate gene approaches. The need for functional data may
      result in a renaissance of biochemical genetics with a new twist in the genomic
      era. We propose that the functional characterization of SNPs and haplotypes be
      advanced with great vigor for those genes with defined assayable phenotypes.
      These systematic investigations will involve classical biochemistry, modern
      genetics, and genomics and will probably also draw on newer technologies such as
      microarrays. In short, a renaissance of biochemical genetics will advance our
      understanding of complex diseases.

PMID- 15464420
TI  - Recent advances in Dyggve-Melchior-Clausen syndrome.
AB  - Dyggve-Melchior-Clausen (DMC) is a rare autosomal-recessive disorder
      characterized by the association of a progressive spondylo-epi-metaphyseal
      dysplasia and mental retardation ranging from mild to severe. Electron microscopy
      studies of both DMC chondrocytes and fibroblasts reveal an enlarged endoplasmic
      reticulum network and a large number of intracytoplasmic membranous vesicles,
      suggesting that DMC syndrome may be a storage disorder. Indeed, DMC phenotype is
      often compared to that of type IV mucopolysaccharidosis (Morquio disease), a
      lysosomal disorder due to either N-acetylgalactosamine-6-sulphatase or beta
      galactosidase deficiency. To date, however, the lysosomal pathway appears normal
      in DMC patients and biochemical analyses failed to reveal any enzymatic
      deficiency or accumulated substrate. Linkage studies using homozygosity mapping
      have led to the localization of the disease-causing gene on chromosome 18q21.1.
      The gene was recently identified as a novel transcript (Dym) encoding a 669-amino
      acid product (Dymeclin) with no known domains or function. Sixteen different Dym
      mutations have now been described in 21 unrelated families with at least five
      founder effects in Morocco, Lebanon, and Guam Island. Smith-MacCort syndrome
      (SMC), a rare variant of DMC syndrome without mental retardation, was shown to be
      allelic of DMC syndrome and to result from mutations in Dym that would be less
      deleterious to the brain. The present review focuses on clinical, radiological,
      and cellular features and evolution of DMC/SMC syndromes and discusses them with
      regard to identified Dym mutations and possible roles of the Dym gene product.

PMID- 15464421
TI  - Molecular mechanisms of DAX1 action.
AB  - DAX1 (dosage sensitive sex reversal (DSS), adrenal hypoplasia congenita (AHC)
      critical region on the X chromosome, gene 1) encoded by the gene NR0B1, is an
      unusual orphan nuclear receptor that when mutated causes AHC with associated
      hypogonadotropic hypogonadism (HH), and when duplicated causes DSS. DAX1
      expression has been shown in all regions of the hypothalamic-pituitary-adrenal
      gonadal (HPAG) axis during development and in adult tissues, suggesting a
      critical role for DAX1 in the normal development and function of this axis.
      Steroidogenic factor 1 (SF1, NR5A1) knockout mice show similar developmental
      defects as AHC and HH patients, but paradoxically, DAX1 is a negative coregulator
      of SF1 transactivation. The function of DAX1 as an antagonist of SF1 in gonadal
      development is consistent with the fact that in humans, duplication of the region
      of the X chromosome containing DAX1 causes a similar phenotype as mutations in
      SF1. However, how disruption of DAX1 leads to adrenal, hypothalamic, and
      pituitary developmental defects similar to SF1 disruption remains to be
      clarified. The exact mechanism of DAX1 action in each of these tissues during
      adulthood and critical stages of development are not fully understood. Recent
      evidence suggests a broader functional role for DAX1 as a negative coregulator of
      estrogen receptor (ER, NR3A1-2), liver receptor homologue-1 (LRH-1, NR5A2),
      androgen receptor (AR, NR3C4), and progesterone receptor (PR, NR3C3), each by
      distinct repression mechanisms. DAX1 may have pleiotropic roles in addition to
      its function as a negative regulator of steroidogenesis during the development
      and adult function of the HPAG axis.

PMID- 15464422
TI  - Genetic screening methods for the detection of mutations responsible for multiple
      endocrine neoplasia type 1.
AB  - Identification of mutations, which cause genetic diseases can be difficult when
      the disease is caused by the mutation of a large gene, which contains multiple
      exons. Detection of these mutations by DNA sequencing can be made more efficient
      by using mutation detection methods for pre-screening to identify the affected
      exon and to screen for the presence of already identified mutations in family
      members. These screening methods include denaturing gradient gel electrophoresis
      (DGGE), temperature gradient gel electrophoresis (TGGE), single-strand
      conformation polymorphism, conformation-sensitive gel electrophoresis (CSGE),
      heteroduplex analysis and denaturing high-performance liquid chromatography
      (DHPLC). We discuss the advantages and shortcomings of these methods by reviewing
      the results of studies screening for mutations causing multiple endocrine
      neoplasia type 1 (MEN 1) syndrome, an autosomal dominant disorder characterized
      by endocrine tumours of the anterior pituitary gland, parathyroid glands, and
      pancreas. MEN 1 is caused by mutations of the MEN1 gene, a tumour suppressor
      gene, which contains one untranslated exon and nine exons. Previous studies have
      identified more than 400 germline and somatic mutations spreading across all the
      encoding sequence, and found no mutational "hot spot" or genotype-phenotype
      correlation. The wide diversity of mutations in the entire coding region of the
      MEN1 gene makes mutation screening time-consuming and expensive. We conclude that
      combination of mutation detection methods with DNA sequencing enhances the
      efficiency of identifying pathogenic mutations. However, it should be considered
      that experimental determination of the optimal electrophoresis conditions, such
      as using perpendicular electrophoresis to optimise DGGE or TGGE, is more useful
      than computerized algorithms to calculate these parameters.

PMID- 15464423
TI  - Death effectors of beta-cell apoptosis in type 1 diabetes.
AB  - While it is generally agreed that apoptosis of pancreatic beta-cells is the most
      important and final step in the progression of type 1 diabetes without which
      clinical diabetes does not develop, it has not been elucidated which molecule(s)
      are the real culprit(s) in type 1 diabetes. Perforin, FasL, TNFalpha, IL-1,
      IFNgamma, and NO have been claimed as the effector molecules; however, they, as a
      single agent, might explain only part of beta-cell death in type 1 diabetes.
      While FasL was initially considered as a strong candidate for the most important
      death effector, following experiments cast doubt on such a hypothesis.
      Combinations or synergism between IFNgamma and TNFalpha or IL-1beta are being
      revisited as the death effectors, and molecular mechanism explaining such a
      synergism was addressed in several recent papers. The role of NF-kappaB for
      pancreatic beta-cell death in type 1 diabetes is also controversial. While NF
      kappaB plays anti-apoptotic roles in most other death models, its role in type 1
      diabetes might be different probably due to the involvement of multiple cytokines
      at different stages of the disease progression and the peculiarity of pancreatic
      beta-cells. Recent papers also suggested a role for Ca2+ in cytokine-mediated
      pancreatic beta-cell death. Such participation of Ca2+ in beta-cell death appears
      to have a close relevance to the mitochondrial events or ER stress that
      constitutes an important part of cell death machinery recently identified.

PMID- 15464424
TI  - Impact of genetic variation of PPARgamma in humans.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription
      factor with a key role in adipocyte differentiation. Since 1997, studies of rare
      mutations and common polymorphisms of the PPARgamma gene have enabled us to
      expand our knowledge of the role of this transcription factor in humans. Rare
      monogenic mutations in PPARgamma have a limited impact on the health of the
      population due to their low frequency but are associated with severe phenotypes
      such as severe insulin resistance, partial lipodystrophy, type 2 diabetes and
      hypertension. Conversely, common polymorphisms of PPARgamma with a relatively
      high frequency can have a significant impact on the general population. Although
      they may modulate the risk of developing type 2 diabetes, obesity and
      cardiovascular diseases, the data remains controversial. This review details and
      discusses results obtained for PPARgamma variants, whose effects sometimes appear
      discordant.

PMID- 15464425
TI  - Differential roles of the Leloir pathway enzymes and metabolites in defining
      galactose sensitivity in yeast.
AB  - The metabolism of galactose via enzymes of the Leloir pathway: galactokinase,
      galactose-1-P uridylyltransferase, and UDP galactose-4'-epimerase, is a process
      that has been conserved from Escherichia coli through humans. Impairment of this
      pathway in patients results in the disease galactosemia. Despite decades of
      study, the underlying pathophysiology in galactosemia remains unknown. Here we
      have defined the functional and metabolic implications of impaired galactose
      metabolism in yeast, by asking two questions: (1) What is the impact of loss of
      each of the three Leloir enzymes on the ability of cells to metabolize galactose,
      and on their sensitivity to galactose, and (2) what is the relationship between
      gal-1P and galactose-sensitivity in yeast? Our results demonstrate that only
      transferase-null cells are able to deplete their medium of galactose; deletion of
      kinase or epimerase halts this process. In contrast, only kinase-null cultures
      grow well in glycerol/ethanol medium despite the addition of galactose; both
      transferase and epimerase-null yeast arrest growth under these conditions.
      Indeed, epimerase-null yeast arrest growth at galactose concentrations 10-fold
      lower than do their transferase-null counterparts. Secondary deletion of kinase
      relieves growth arrest in both strains. Finally, rather than a continuous
      relationship between gal-1P and growth arrest, we observed a threshold level of
      gal-1P (approximately 10 nmol/mg cell DM) above which both transferase-null and
      epimerase-null cultures could not grow. These results both confirm and
      significantly extend prior knowledge of galactose metabolism in yeast, and set
      the stage for future studies into the mediators and mechanism of Leloir-impaired
      galactose sensitivity in eukaryotes.

PMID- 15464426
TI  - X-linked adrenoleukodystrophy: role of very long-chain acyl-CoA synthetases.
AB  - The principal biochemical abnormality in the neurodegenerative disorder X-linked
      adrenoleukodystrophy (X-ALD) is elevated plasma and tissue levels of very long
      chain fatty acids (VLCFA). Enzymes with very long-chain acyl-CoA synthetase
      (VLACS) activity are required for VLCFA metabolism, including degradation by
      peroxisomal beta-oxidation or incorporation into complex lipids, and may also
      participate in VLCFA synthesis. Two enzymes with VLACS activity, ACSVL1 and BG1,
      were investigated for their potential role in X-ALD biochemical pathology. Skin
      fibroblast mRNA levels for ACSVL1, an enzyme previously shown to be in
      peroxisomes and to participate in VLCFA beta-oxidation, were not significantly
      different between normal controls, patients with childhood cerebral X-ALD, and
      patients with adrenomyeloneuropathy. Similar results were obtained with mRNA for
      BG1, a non-peroxisomal enzyme that is highly expressed in nervous system, adrenal
      gland, and testis, the principal tissues pathologically affected in X-ALD. No
      significant differences in the immunohistochemical staining patterns of tissues
      expressing either ACSVL1 or BG1 were observed when wild-type and X-ALD mice were
      compared. Western blot analysis of BG1 protein levels showed no differences
      between fibroblasts from controls, cerebral X-ALD, or adrenomyeloneuropathy
      patients. BG1 protein levels were similar in wild-type and X-ALD mouse brain,
      spinal cord, testis, and adrenal gland. We hypothesized that one function of BG1
      was to direct VLCFA into the cholesterol ester synthesis pathway. However, BG1
      depletion in Neuro2a cells using RNA interference did not decrease incorporation
      of labeled VLCFA into cholesterol esters. We conclude that the role, if any, of
      ACSVL1 and BG1 in X-ALD biochemical pathology is indirect.

PMID- 15464427
TI  - Electroretinographic and clinicopathologic correlations of retinal dysfunction in
      infantile neuronal ceroid lipofuscinosis (infantile Batten disease).
AB  - Infantile neuronal ceroid lipofuscinosis (INCL) is an autosomal recessive disease
      that results from deficiency of palmitoyl-protein thioesterase-1 (PPT1). INCL
      leads to retinal blindness, neurodegeneration, and early death. We studied the
      clinical features and electroretinogram (ERG) in three patients and
      histopathologic and immunofluorescence analyses of the retina in the third
      patient, who died at 3 years 2 months of age. The ERGs for the 2 youngest
      patients (ages 1.7 and 2.3 years) showed normal scotopic bright flash a-wave
      amplitudes with severe loss of b-wave (electronegative ERG), indicating
      dysfunction at or proximal to the photoreceptor inner segments. The third patient
      at 2.9 years of age showed subnormal a-wave amplitudes and even greater loss of b
      wave amplitudes. Histopathology revealed reduced cell numbers in all retinal
      layers, including the inner nuclear layer (INL), and a central epiretinal
      membrane. Autofluorescent lipofuscin granules were present in all neuronal cell
      types in the retina. Cones and rods in the parafoveal area were labeled with a
      cone cytoplasmic marker, mAb 7G6, and anti-rhodopsin, respectively, and had
      extremely short outer segments. The periphery showed better preservation but
      photoreceptor outer segments were short. Immunofluorescence revealed degenerate
      rods and cones throughout the retina with better preservation in the periphery.
      Autofluorescent lipofuscin was found in all cell types, including cone inner
      segments, to a greater degree than seen in normal ageing. The ERG findings
      support the existence early in the disease of a relative pre- or post-synaptic
      block of effective neurotransmission from photoreceptor inner segments to the
      second order bipolar neurons.

PMID- 15464428
TI  - Chronic treatment of mitochondrial disease patients with dichloroacetate.
AB  - Clinical features are reported for 37 patients with various mitochondrial
      disorders, treated with sodium dichloroacetate (DCA) for 3 weeks to 7 years (mean
      3.25 years) at 11-50 mg/kg/day (34.6+/-13.1) in an open-label format. DCA
      pharmacokinetics showed half-times approximately 86 min for the first intravenous
      dose of 50 mg/kg, 3.2 h for a subsequent intravenous dose 4-6 h later, and 11 h
      after continued oral dosing of 12.5-25 mg/kg twice daily. Basal blood and CSF
      lactate (mean values at entry 29.6 and 46.8 mg/dL, respectively) decreased at 3
      months (to 18.1 and 34.2, respectively) and 12 months (to 17.7 and 33.1,
      respectively). There was some attenuation of the blood lactate response to oral
      fructose but not glucose, although the baseline lactate was lower with DCA. A
      standardized neurologic inventory showed stabilization or improvement over one
      year. The subjective impression of overall disease course was worsening in 21.6%,
      improvement in 48.6%, and no discernable effect in 29.7%. Among 8 patients who
      had 17 stroke-like events in 0.25-5 years prior to study entry, there were a
      total of 2 events over 3-6 years of treatment. In two cases institution of DCA
      resulted in dramatic relief of severe headaches which had been refractory to
      narcotics. Given variability of symptoms and limited understanding of natural
      history of mitochondrial disease, it is difficult to determine the efficacy of
      DCA in this open-label study, but there did appear to be some cases in which
      there were at least temporary benefits.

PMID- 15464429
TI  - Wild-type phenylalanine hydroxylase activity is enhanced by tetrahydrobiopterin
      supplementation in vivo: an implication for therapeutic basis of
      tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency.
AB  - We previously proposed a novel disease entity, tetrahydrobiopterin (BH4)
      responsive phenylalanine hydroxylase (PAH) deficiency, in which administration of
      BH4 reduced elevated levels of serum phenylalanine [J. Pediatr. 135 (1999) 375
      378]. Subsequent reports indicate that the prevalence of BH4-responsive PAH
      deficiency is much higher than initially anticipated. Although growing attention
      surrounds treatment with BH4, little is known about the mechanism of BH4
      responsiveness. An early report indicates that BH4 concentration in rat liver was
      5 microM where Km for BH4 of rat PAH was estimated to be 25 microM in an
      oxidation experiment using a liver slice, suggesting relative insufficiency of
      BH4 in liver in vivo. In the present study, we developed a breath test for mice
      using [1-13C]phenylalanine in order to examine the BH4 responsiveness of normal
      PAH in vivo. The reliability of the test was verified using BTBR mice and its
      mutant strain lacking PAH activity, Pahenu2. BH4 supplementation significantly
      enhanced 13CO2 production in C57BL/6 mice when phenylalanine was pre-loaded.
      Furthermore, BH4 apparently activated PAH in just 5 min. These observations
      suggest that submaximal PAH activity occurs at the physiological concentrations
      of BH4 in vivo, and that PAH activity can be rapidly enhanced by supplementation
      with BH4. Thus, we propose a possible hypothesis that the responsiveness to BH4
      in patients with PAH deficiency is due to the fact that suboptimal physiological
      concentrations of BH4 are normally present in hepatocytes and the enhancement of
      the residual activity may be associated with a wide range of mutations.

PMID- 15464430
TI  - Tetrahydrobiopterin responsiveness: results of the BH4 loading test in 31 Spanish
      PKU patients and correlation with their genotype.
AB  - Tetrahydrobiopterin (BH4) responsiveness in patients with mutations in the
      phenylalanine hydroxylase (PAH) gene is a recently recognized subtype of
      hyperphenylalaninemia characterized by a positive BH4 loading test. According to
      recent estimates, this phenotype may be quite common, suggesting that a large
      group of individuals may benefit from BH4 substitution, eliminating the need of
      life-long dietary restrictions. This underscores the importance of identifying
      BH4-responsive patients in each population, establishing the association with
      specific PAH mutations. In this work, we describe the results of a pilot study
      performed with 31 Spanish PAH-deficient patients subjected to a BH4 loading test.
      Overall, 11/31 (37%) showed a positive response with a 30% decrease in blood Phe
      levels 8 h after the BH4 challenge, and three additional patients, considered
      slow responders, showed this decrease only after 12-16 h. We report for the first
      time a patient homozygous for a splicing mutation with a slow response,
      suggesting an effect of BH4 supplementation on PAH gene expression. Most of the
      responsive patients belong to the mild hyperphenylalaninemia (MHP) or mild
      phenylketonuria phenotypic groups. In MHP patients we report for the first time
      the results of parallel single Phe doses confirming the utility of these analyses
      for a better evaluation of the response. Genotype analysis confirms the
      involvement in the response of specific mutations (D415N, S87R, R176L, E390G, and
      A309V) present in hemizygous patients, and provide relevant information for the
      discussion of the potential mechanisms underlying BH4 responsiveness.

PMID- 15464431
TI  - Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and
      meninges of the canine model of MPS I.
AB  - Enzyme replacement therapy (ERT) has been developed for several lysosomal storage
      disorders, including mucopolysaccharidosis I (MPS I), and is effective at
      reducing lysosomal storage in many tissues and in ameliorating clinical disease.
      However, intravenous ERT does not adequately treat storage disease in the central
      nervous system (CNS), presumably due to effects of the blood-brain barrier on
      enzyme distribution. To circumvent this barrier, we studied whether intrathecal
      (IT) recombinant human alpha-L-iduronidase (rhIDU) could penetrate and treat the
      brain and meninges. An initial dose-response study showed that doses of 0.46-4.14
      mg of IT rhIDU successfully penetrated the brain of normal dogs and reached
      tissue levels 5.6 to 18.9-fold normal overall and 2.7 to 5.9-fold normal in deep
      brain sections lacking CSF contact. To assess the efficacy and safety in treating
      lysosomal storage disease, four weekly doses of approximately 1 mg of IT rhIDU
      were administered to MPS I-affected dogs resulting in a mean 23- and 300-fold
      normal levels of iduronidase in total brain and meninges, respectively.
      Quantitative glycosaminoglycan (GAG) analysis showed that the IT treatment
      reduced mean total brain GAG to normal levels and achieved a 57% reduction in
      meningeal GAG levels accompanied by histologic improvement in lysosomal storage
      in all cell types. The dogs did develop a dose-dependent immune response against
      the recombinant human protein and a meningeal lymphocytic/plasmacytic infiltrate.
      The IT route of ERT administration may be an effective way to treat the CNS
      disease in MPS I and could be applicable to other lysosomal storage disorders.

PMID- 15464432
TI  - Lowered DHCR7 activity measured by ergosterol conversion in multiple cell types
      in Smith-Lemli-Opitz syndrome.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of
      cholesterol metabolism characterized by multiple congenital anomalies and mental
      retardation. SLOS results from mutations in 7-dehydrocholesterol Delta7 reductase
      (DHCR7), the gene encoding the final enzyme involved in cholesterol biosynthesis.
      The resulting cholesterol deficiency and excessive 7- and 8-dehydrocholesterol (7
      DHC, 8-DHC) in plasma and tissues are almost always diagnostic for SLOS. We
      measured DHCR7 activity in fibroblasts, amniocytes, and chorionic villi from
      controls, heterozygotes, and SLOS subjects. The enzyme activity (expressed as
      percent conversion of substrate) was significantly lower in untransformed
      fibroblasts from SLOS subjects (4.47%+/-0.72) compared to untransformed
      fibroblasts from heterozygotes (26.6%+/-4.6, p<0.01) or controls (50.6%+/-5.3,
      p<0.001). We also measured plasma cholesterol and 7-DHC, determined the severity
      score and identified DHCR7 mutations for most of the subjects. There was no
      significant correlation of enzyme activity with severity score, plasma
      cholesterol level, plasma 7-DHC level, or the 7-DHC:cholesterol ratio. We
      conclude that even though enzyme activity as measured by the ergosterol assay may
      not correlate with severity, this assay has the potential to distinguish SLOS
      cells from carrier or unaffected cells in a variety of cell types, and should
      prove useful in confirming a diagnosis in atypical cases where sterol levels are
      equivocal. Additionally, it may be important to measure residual enzyme activity
      in SLOS subjects being considered for a trial of statins, as this treatment could
      theoretically be detrimental in subjects with little or no DHCR7 activity.
      Finally, the data suggest a threshold enzyme activity of 8% conversion, below
      which disease occurs.

PMID- 15464433
TI  - T0901317 is a dual LXR/FXR agonist.
AB  - We characterize the ability of the liver X receptor (LXRalpha [NR1H3] and LXRbeta
      [NR1H2]) agonist, T0901317, to activate the farnesoid X receptor (FXR [NR4H4]).
      Although T0901317 is a much more potent activator of LXR than FXR, this ligand
      actually activates FXR more potently than a natural bile acid FXR ligand,
      chenodeoxycholic acid. Thus, the FXR activity of T0901317 must be considered when
      utilizing this agonist as a pharmacological tool to investigate LXR function.

PMID- 15464434
TI  - Novel troponin T mutation in familial dilated cardiomyopathy with gender
      dependant severity.
AB  - Mutations in sarcomeric proteins can lead to either hypertrophic or dilated
      cardiomyopathy depending on their effects on the structural and functional
      properties of the contractile unit of the heart. Mutations in cardiac troponin T,
      which binds the calcium-responsive troponin complex to alpha-tropomyosin, have
      been shown to result in cardiac hypertrophy or cardiac dilatation and heart
      failure, depending on the nature of the specific mutation. In this study, we
      report the identification of a novel cardiac troponin T mutation (A171S) leading
      to dilated cardiomyopathy and sudden cardiac death. In contrast to prior
      described mutations, the A171S mutation results in a significant gender
      difference in the severity of the observed phenotype with adult males (over 20
      years of age) demonstrating more severe ventricular dilatation [left ventricular
      end diastolic dimension (LVEDD) 7.1 vs. 5.1cm; P=0.01, t test] and left
      ventricular dysfunction [left ventricular shortening fraction (LVSF) 21 vs. 34%;
      P=0.04, t test] than adult females. The described mutation substitutes a
      hydrophilic amino acid for a hydrophobic one in a highly conserved domain
      involved in the interaction between troponin T and alpha-tropomyosin.
      Interestingly, four previously described mutations within 12 amino acids of A171
      lead to a hypertrophic phenotype, suggesting that further characterization of the
      functional consequences of the A171S mutation may lead to a better understanding
      of the pathophysiology of DCM and of the functional differences between HCM- and
      DCM-causing mutations in cardiac troponin T.

PMID- 15464435
TI  - Vitamin D 25-hydroxylase deficiency.

PMID- 15464436
TI  - The genes encoding cAMP-dependent protein kinase catalytic subunit homologues of
      the microsporidia Encephalitozoon intestinalis and E. cuniculi: molecular
      characterisation and phylogenetic analysis.
AB  - A gene encoding a protein kinase was identified by homology-based PCR
      amplification in Encephalitozoon intestinalis, a microsporidian parasite
      pathogenic to humans, and its orthologue has been identified by database mining
      in the genome of the related species E. cuniculi, whose sequence has been
      recently published. Phylogenetic analysis revealed that the proteins encoded by
      these genes are homologues of the cAMP-dependent protein kinase catalytic
      subunits (PKAc). Southern blot analysis indicated that the EiPKAc gene is present
      in two copies in the E. intestinalis genome, whereas the E. cuniculi orthologue
      (EcPKAc) is a single copy gene. RT-PCR data showed that the EiPKAc gene is
      expressed in at least one of the intracellular stages during infection of the
      mammalian host cell by E. intestinalis.

PMID- 15464437
TI  - Anthelmintic efficacy of genistein, the active principle of Flemingia vestita
      (Fabaceae): alterations in the free amino acid pool and ammonia levels in the
      fluke, Fasciolopsis buski.
AB  - The crude root-peel extract of Flemingia vestita, its active principle genistein
      and the reference flukicide oxyclozanide were tested against Fasciolopsis buski,
      the giant intestinal trematode. The amino acid composition of F. buski was
      demonstrated using HPLC and it was observed that the free amino acid (FAA) pool
      of the control worm consisted of aspartate, threonine, serine, glutamic acid,
      glutamine, proline, glycine, alanine, valine, methionine, isoleucine, leucine,
      tyrosine, lysine, histidine, arginine, phosphoserine, taurine, citrulline,
      ornithine, beta-alanine, and gamma-amino butyric acid (GABA). Of the amino acids
      detected valine was found to be the maximum in quantitative analysis. In
      qualitative analysis the FAA pool of the parasites under various treatments
      remained same as that of the control; however, quantitatively the level of
      various FAAs in the parasite was significantly affected. The treated parasites
      showed a marked decrease in the levels of arginine, ornithine, tyrosine, leucine,
      isoleucine, valine, alanine, glycine, proline, serine, threonine, and taurine
      following treatment with 20 mg/ml of crude peel extract, 0.5 mg/ml of genistein
      and 20 mg/ml of the reference drug, though an increase in the levels of glutamic
      acid, glutamine, phosphoserine, citrulline and GABA was noticeable. Enhanced
      levels of GABA and citrulline under the influence of genistein may be implicated
      in alterations of nitric oxide release and consequent neurological change (e.g.
      paralysis) in the parasite. Ammonia in the tissue homogenate as well as in the
      incubation medium showed a quantitative increase compared to the controls after
      treatment with the various test materials. The ammonia level increased by 40.7%,
      66.4% and 18.16% in treatments with F. vestita, genistein and oxyclozanide,
      respectively, at the mentioned dosages. The changes in the levels of the amino
      acids and nitrogen components post treatment suggest that the amino acid
      metabolism in the parasite may have been altered under the influence of the test
      materials.

PMID- 15464438
TI  - The miniature pig: a unique experimental model for Schistosoma japonicum
      infection.
AB  - As part of a search for good animal models for human schistosomiasis, two
      miniature pigs of the CLAWN strain (C-1, C-2) were inoculated percutaneously with
      200 Schistosoma japonicum cercariae of the Chinese strain, and the subsequent
      infection was monitored parasitologically, pathologically and serologically. Egg
      excretion into feces began at 5 weeks post-infection (p.i.) and became pronounced
      from 8 weeks to 17-20 weeks p.i. The average number of eggs in 1 g feces of each
      pig at the peak period between 8 and 20 weeks were 288 and 277, respectively. C-1
      and C-2 were killed and perfused at 27 and 47 weeks p.i. and adult worm numbers
      recovered were 35 and 15, respectively. C-2 had at least four pairs of viable
      mature worms but no detectable fecal eggs for a month before perfusion,
      suggesting that any produced eggs were not excreted into the feces during this
      period. Egg deposits associated with inflammatory reactions were observed by
      histological examination of the liver, spleen, pancreas, mesenteric lymph nodes,
      lung, and small intestine. This suggests that reduced fecal excretion of eggs
      into the feces did not correlate to reduced parasite numbers in the chronic phase
      of schistosomiasis. This is the first report showing the miniature pig to be a
      potential model for human S. japonicum infection.

PMID- 15464439
TI  - Growth and development of Massaliatrema misgurni (Trematoda: Heterophyidae) in
      mice and its metacercarial morphology.
AB  - The morphology of metacercariae of Massaliatrema misgurni Ohyama et al. (Ohyama
      et al., Parasitol Int 2001; 50; 267-71) was described, and their infectivity, egg
      output, growth and development in mice until day 35 post infection (PI) were
      studied. Metacercarial cysts from loaches imported from China to Japan were 199
      349 microm in diameter and consisted of a very thick translucent outer layer and
      a refractile inner layer. Excysted metacercariae basically had the shape of
      miniature adults, and a pair of pre-developed testes but no other genital organs
      were recognized. The worm recovery rate from mice was 36.7-51.7% during days 3-7
      PI, and decreased remarkably to 2.5 and 1.7% at days 28 and 35 PI. The prepatent
      period was 3-4 days, and the egg output quickly increased and sustained high
      levels at days 5-7 PI, then decreased suddenly at day 8 PI, and continued at a
      low level until day 28 PI. The size of the body and inner organs such as the oral
      sucker, pharynx, acetabulum, testes, ovary and seminal receptacle quickly
      increased until day 3 PI, and sustained at a plateau level until day 21 PI except
      testes which gradually decreased until 21 PI. The number of the uterine eggs
      increased with a short time lag compared to other genital organs and sustained a
      plateau level until day 21 PI. Compared with other Heterophyidae species, M.
      misgurni was characterized by the remarkably fast growth and development.

PMID- 15464440
TI  - Flight muscle-specific expression of act88F: GFP in transgenic Culex
      quinquefasciatus Say (Diptera: Culicidae).
AB  - A strategy to engineer a strain of Culex mosquitoes refractory to filarial
      transmission is described. A requirement for success of the strategy is
      identification of a flight muscle-specific promoter that functions in the
      mosquito. A GFP marker gene under the control of the promoter region of the
      Drosophila melanogaster act88F gene was inserted into the genome of Culex
      quinquefasciatus. Transformation was confirmed by Mendelian genetics.
      Hybridization of a genomic Southern blot to a radiolabeled probe verified that
      the entire donor plasmid integrated into the mosquito genome. GFP expression in
      the transgenic mosquitoes was restricted to the flight muscles.

PMID- 15464441
TI  - Effect of treatment with free and liposomized albendazole on selected
      immunological parameters and cyst growth in mice infected with Echinococcus
      multilocularis.
AB  - Selected immunological parameters in healthy mice and mice infected with
      Echinococcus multilocularis and the effect of free and liposomized albendazole
      (lip.ABZ) upon these parameters in relation to the reduction of parasite growth
      were investigated over 26 weeks. Proliferative response of splenic T and B
      lymphocytes, number of CD4+ and CD8+ spleen T cell subpopulations, serum
      concentration of IFN-gamma and IL-5, and generation of superoxide anion (O2-) by
      peritoneal macrophages were the chosen parameters. Both drug forms were given to
      mice at a dose of 10 mg kg(-1) twice a week from week 4 to week 10 post infection
      (p.i.) (6 weeks in total). The reduction of cyst growth after treatment with ABZ
      and lip.ABZ was similar up to week 4 after last dose, but the parasitostatic
      effect of lip.ABZ lasted 4 weeks longer than the effect of free drug. After
      administration of both drug forms, the proliferative responses of T and B cells
      were restored, and also the number of CD4+ and CD8+ increased markedly. In
      lip.ABZ-treated mice, stimulation of mentioned lymphocyte parameters, except that
      of CD8+ numbers, persisted for longer period than after ABZ therapy, where values
      peaked at week 12 p.i., then declined more rapidly. A very strong stimulatory
      effect was seen on B lymphocytes during the period of lip.ABZ administration,
      although interestingly, numbers of CD8+ cells were higher in free ABZ-treated
      group. Low concentrations of IFN-gamma (Th1 response) were present in infected,
      untreated mouse serum. Only moderate IFN-gamma elevation was observed after
      treatment with free ABZ. A profound increase of its concentration was seen
      shortly after administration of lip.ABZ, and persisted until the experiment
      ended. In infected untreated mice, concentration of IL-5 (Th2 response) was
      highest on week 2 p.i. Significantly more IL-5 was recorded in serum of mice
      treated with free ABZ treatment than with lip.ABZ from week 12 to 18 p.i. (weeks
      2-8 after the last dose). After the initial increase of superoxide anions (weeks
      4-11 p.i.), generation of O2- by peritoneal macrophages was gradually inhibited
      by E. multilcoularis infection. In general, treatment abolished this suppression
      and macrophages from lip.ABZ-treated mice produced elevated amounts of O2- over a
      longer period than macrophages from ABZ-treated mice. Our data indicate that
      anthelmintic potency of ABZ could be increased after incorporation into
      liposomes, not only because of improved pharmacokinetics and consequent
      bioavailability, but also because of significant stimulation of Th1-type cytokine
      IFN-gamma response and effector macrophage functions.

PMID- 15464442
TI  - Two new blood flukes (Digenea: Sanguinicolidae) from Epinephelinae (Perciformes:
      Serranidae) of the Pacific Ocean.
AB  - Pearsonellum pygmaeus n. sp. is described from Cromileptes altivelis
      (Serranidae), the Barramundi Cod, from Heron Island (southern Great Barrier Reef)
      and Lizard Island (northern Great Barrier Reef). This new species differs from
      Pearsonellum corventum (type and only species) in the combination of smaller
      overall body size, the relative distance of the brain from the anterior end, the
      relative lengths of both the oesophagus and the testis, the degree to which the
      testis extends outside the intercaecal field, the shape of the testis, the shape
      and size of the ovary and the extent to which the uterus loops around the ovary.
      There are in addition, 20 base pair differences between the ITS2 rDNA sequence of
      P. pygmaeus n. sp. and that of P. corventum. Three new host records for P.
      corventum are reported. Adelomyllos teenae n. g., n. sp. is described from
      Epinephelus coioides (Serranidae), the Estuary Cod, from Moreton Bay, southeast
      Queensland. The new genus differs from the 22 other sanguinicolid genera in the
      combined possession of two testes, a cirrus-sac, separate genital pores, a post
      ovarian uterus and an H-shaped intestine. A. teenae n. sp. is the third
      sanguinicolid described from the Epinephelinae. Sanguinicolids have now been
      reported from 11 species of Serranidae.

PMID- 15464443
TI  - Genotypic variation among lineages of Trypanosoma cruzi and its geographic
      aspects.
AB  - Isozyme analysis with 18 enzyme loci was conducted on 146 isolates of Trypanosoma
      cruzi from Mexico, Guatemala, Colombia, Ecuador, Peru, Brazil, Bolivia, Paraguay
      and Chile. Forty-four different MLGs (groups of isolates with identical
      multilocus genotypes) were identified and a phylogeny was constructed. The
      phylogenetic tree consisted of two main groups (T. cruzi I, T. cruzi II), and the
      latter was further divided into two subgroups (T. cruzi IIa, T. cruzi IIb-e).
      Evidence of hybridization between different MLGs of T. cruzi II was found, which
      means that genetic exchanges seem to have occurred in South American T. cruzi. On
      the other hand, the persistence of characteristic T. cruzi I and T. cruzi II
      isozyme patterns in single small villages in Bolivia and Guatemala suggested that
      genetic exchange is very rare between major lineages. A significant difference in
      genetic diversity was shown between T. cruzi I and T. cruzi II from several
      indices of population genetics. Two possibilities could explain this genetic
      variation in the population: differences in evolutionary history and/or different
      tendencies to exchange genetic material. Broad-scale geographic distributions of
      T. cruzi I and T. cruzi IIb-e were different; T. cruzi I occurred in Central
      America and south to Bolivia and Brazil, while T. cruzi IIb-e occurred in the
      central and southern areas of South America, overlapping with T. cruzi I in
      Brazil and Bolivia.

PMID- 15464445
TI  - Some like it hot: curcumin and CFTR.
AB  - The activation of mutant forms of the cystic fibrosis transmembrane conductance
      regulator (CFTR), particularly the most frequent mutant allele (DeltaF508), is a
      potential strategy for the treatment of the disease cystic fibrosis (CF).
      Therefore, it is of great interest that curcumin, a component of the spice
      turmeric, is reported to restore function to this allele, both in heterologous
      expression systems and in DeltaF508 CF mice. Although other laboratories have not
      been able to confirm the initial observations, activating DeltaF508 CFTR could
      have such important therapeutic implications that a thorough investigation of the
      potential of curcumin is warranted.

PMID- 15464444
TI  - Anthelmintic efficacy of Flemingia vestita (Fabaceae): alterations in glucose
      metabolism of the cestode, Raillietina echinobothrida.
AB  - The root-tuber peel of Flemingia vestita and its active component, genistein,
      were tested in respect of glucose metabolism in the cestode, Raillietina
      echinobothrida. Live R. echinobothrida, collected from the intestine of freshly
      slaughtered domestic fowl, were incubated at 39+/-1 degrees C in defined
      concentrations of the root-peel crude extract (5 mg/ml), genistein (0.2 mg/ml)
      and praziquantel (1 microg/ml) in phosphate buffered saline with 1% of dimethyl
      sulphoxide with simultaneous maintenance of controls. In the treated worms, there
      was a significant decrease in the glycogen concentration accompanied with the
      decrease of glucose by 14-32%, whereas the malate concentration increased by 49
      134% as compared to controls. Both in controls and treated parasites, however,
      the pyruvate content was not measurable. While alanine and lactate contents
      showed a decline by 7-25% in the parasites exposed to all test materials, the
      lactate efflux into the incubation medium showed 37-71% increase in treatments
      indicating an overall increase of lactate production in comparison to controls.
      The results showing a decline in the glycogen and glucose contents and a
      significant rise in the malate content and lactate efflux under treatment
      conditions suggest that the energy demand in the parasites possibly got enhanced
      under stress, though it did not influence a switch over towards aerobic
      degradation of glucose in the parasites.

PMID- 15464446
TI  - Dual role of DENN/MADD (Rab3GEP) in neurotransmission and neuroprotection.
AB  - DENN/MADD is a component of a signalling protein complex that is localized to the
      cytosol and exerts multiple functions by using different binding partners. Human
      DENN/MADD is physically the same death-domain protein as rat Rab3 GDP/GTP
      exchange protein (Rab3GEP). DENN/MADD regulates the recycling of Rab3 small G
      proteins under normal conditions and has an essential role in Ca(2+)-dependent
      neurotransmitter release and exocytosis. It is also involved in blocking the
      apoptosis of neuronal cells under conditions of cytotoxic stress. Recent research
      supports an important role for DENN/MADD in neuroprotection: reduced endogenous
      DENN/MADD expression and enhanced pro-apoptotic signalling has been found in
      brains affected by Alzheimer's disease.

PMID- 15464447
TI  - Mutations and addiction to EGFR: the Achilles 'heal' of lung cancers?
AB  - The epidermal growth factor receptor (EGFR) gene product is a receptor tyrosine
      kinase (TK) that affects many important downstream pathways. The recent finding
      that mutations in EGFR predict the response of lung cancers to therapies that
      target the TK domain of the gene product has generated considerable interest. The
      mutations are associated with adenocarcinoma histology, oriental origin, female
      gender and never-smoker status. Most mutations target structures in the TK domain
      that appear to be essential for the phosphorylation function of the gene. Cancer
      cells with mutant EGFR genes might become physiologically dependent on the
      continued activity of the gene for the maintenance of their malignant phenotype;
      however, this might also be a target for therapy.

PMID- 15464448
TI  - Targeting Plasmodium host cells: survival within hepatocytes.
AB  - Upon entering their host, Plasmodium sporozoites travel directly to the liver.
      Once there, they migrate through several hepatocytes before they infect a final
      one. During migration, sporozoites breach the plasma membrane of traversed
      hepatocytes, but to infect they must form a parasitophorous vacuole, in which the
      intra-hepatic form of the parasite grows and multiplies. During this period there
      is a remarkable parasite multiplication, but little is known about the
      requirements and strategies that are developed to be successful. Hepatocyte
      growth factor and its receptor on hepatocytes might enhance early Plasmodium
      development within these cells. We anticipate that this might be the basis for
      further studies on host-cell requirements for Plasmodium development.

PMID- 15464449
TI  - Interleukin-4 receptor signaling pathways in asthma pathogenesis.
AB  - Asthma is a chronic allergic inflammatory disease, the initiation and progression
      of which is dependent on the cytokines interleukin (IL)-4 and IL-13 acting
      through related receptor complexes. Disease pathogenesis is effected by
      intracellular signaling pathways that couple primarily to specific motifs within
      the intracellular domain of the IL-4 receptor alpha chain (IL-4Ralpha), a subunit
      that is common to the IL-4 and IL-13 receptor complexes. Recent studies using
      genetic approaches have identified distinct functions for the respective IL
      4Ralpha-coupled signaling pathways in regulating both early and chronic stages of
      asthma. Polymorphisms in components of the IL-4 and IL-13 cytokine-receptor axes
      are associated with allergy and asthma, suggesting that variations among
      individuals in the activity of this pathway contribute to disease susceptibility
      and manifestations.

PMID- 15464450
TI  - MLL: a histone methyltransferase disrupted in leukemia.
AB  - Rearrangements of the MLL gene, which is located at chromosome 11q23, are
      associated with aggressive acute leukemias in both children and adults. MLL
      regulates Hox gene expression through direct promoter binding and histone
      modification. MLL rearrangements occurring in leukemia include MLL fusion genes,
      partial tandem duplications of MLL and MLL amplification. MLL fusions and
      amplification upregulate Hox expression, apparently resulting in a block of
      hematopoietic differentiation. Future therapies for MLL-associated leukemia might
      involve blocking Hox gene upregulation by using fusion proteins or inhibiting the
      activity of Hox proteins themselves.

PMID- 15464451
TI  - Retinoic-acid-induced apoptosis in leukemia cells.
AB  - Retinoic acid (RA) cures more than 75% of patients with acute promyelocytic
      leukemia (APL). Here, we review the various anti-cancer activities of retinoids
      and rexinoids, alone and in combination with other drugs, with emphasis on the RA
      dependent induction of a cancer-cell-selective apoptosis signaling pathway to
      which multiple anti-cancer signals converge. These findings identify the TRAIL
      (tumor-necrosis-factor-related apoptosis-inducing ligand) pathway as a central
      cell-autonomous anti-cancer weapon that can act independently of the immune
      system.

PMID- 15464452
TI  - New therapies for muscular dystrophy: cautious optimism.
AB  - The quest for a therapy for muscular dystrophy has been the driving force behind
      the past 40 years of advances in this field. Numerous results, such as the
      identification of satellite cells and gene mutations that are responsible for
      most forms of dystrophies, advances in gene transfer and modification technology
      and, more recently, stem cells, have fueled hopes. However, administering
      corticosteroids still remains the only effective treatment available. Several
      recent advances have uncovered a diversity of possible therapeutic approaches,
      from pharmacological treatments to gene therapy (exon-skipping and adeno
      associated viruses) and cell therapy with different types of newly identified
      stem cells. Importantly, a combination of these strategies might greatly enhance
      the possibility of successful therapy.

PMID- 15464453
TI  - Combined late diagnosed right main bronchial disruption and chylothorax from
      blunt chest trauma.
AB  - Both main bronchial disruption and chylothorax are uncommon injuries associated
      with blunt thoracic trauma. We report the case of a patient who presented late
      after traumatic rupture of the right main bronchus who also had a traumatic
      chylothorax.

PMID- 15464454
TI  - Robotically-assisted left atrial fibrillation ablation and mitral valve repair
      through a right mini-thoracotomy.
AB  - A combined robotic-assisted left atrial ablation and mitral valve repair was done
      through a 5-cm right anterior mini-thoracotomy. The patient was a 54-year-old man
      with severe mitral regurgitation and a 10-month history of persistent atrial
      fibrillation. The patient underwent off-pump, beating heart epicardial
      peripulmonary vein microwave ablation using the FLEX 10 catheter (AFx Inc,
      Fremont, CA), followed by supplemental on-pump endocardial lesions. The procedure
      was done using the da Vinci surgical robot (Intuitive Surgical Inc, Sunnyvale,
      CA). The mitral valve repair consisted of a No. 38 Cosgrove annuloplasty band
      implantation (Edwards Life Sciences, LLC, Irvine, CA). The postoperative recovery
      was uneventful, and the patient maintained normal sinus rhythm.

PMID- 15464455
TI  - Aneurysm of the mitral valve: a rare complication of aortic valve endocarditis.
AB  - A 45-year-old man presented to our hospital with severe dyspnea 4 months after
      antibiotic treatment for aortic valve endocarditis. Transesophageal
      echocardiography revealed severe aortic regurgitation and an aneurysm of the
      anterior leaflet of the mitral valve. In addition to aortic valve replacement, we
      excised the aneurysm and repaired the anterior leaflet of the mitral valve.
      Clinical suspicion, appropriate preoperative imaging, and timely surgical
      intervention are essential to recognize and treat this rare complication of
      bacterial endocarditis.

PMID- 15464456
TI  - Pulmonary artery dissection and rupture associated with aortopulmonary window.
AB  - A 31-year-old man with uncorrected aortopulmonary window and fixed pulmonary
      hypertension experienced dissection of the pulmonary artery, rapidly complicated
      by a fatal spontaneous rupture into the pericardium. In the setting of pulmonary
      hypertension, the diagnosis of dissection and rupture of the pulmonary artery
      should be considered in cases of thoracic pain or cardiogenic shock.

PMID- 15464457
TI  - Complete atrioventricular canal and tetralogy of Fallot with pulmonary atresia.
AB  - Our patient was diagnosed with complete atrioventricular canal and Tetralogy of
      Fallot with pulmonary atresia at the age of 1 month. Then he underwent right and
      left Blalock-Taussig shunts at the ages of 2 months and 5 years, respectively.
      His cyanosis had increased at 20 years of age. Cardiac catheterization showed
      occlusion of the left Blalock-Taussig shunt and absence of the left pulmonary
      artery. Lung perfusion scintigram showed late phase perfusion in the left lung.
      Chest computed tomographic scan demonstrated the left pulmonary artery. We
      describe the operative technique of total correction.

PMID- 15464458
TI  - Right ventricular pseudoaneurysm after modified Norwood procedure.

PMID- 15464459
TI  - Pleural partition with intrathoracic muscle transposition (muscle tent) to manage
      residual spaces after subtotal pulmonary resections.
AB  - The concept of separating the pleural cavity to better control residual spaces
      has been revisited by introducing a technique of pleural partition through
      transposed chest wall muscles (muscle tent). This technique has been successfully
      used in 3 patients with severe lung destruction due to chronic infections who
      required subtotal pulmonary resections.

PMID- 15464460
TI  - Mentorship, women thoracic surgeons, and the thoracic surgery foundation for
      research and education.

PMID- 15464461
TI  - Are thoracic surgeons ethically obligated to serve as expert witnesses for the
      plaintiff? Pro.

PMID- 15464462
TI  - J. Maxwell Chamberlain Memorial Paper. Early fundoplication prevents chronic
      allograft dysfunction in patients with gastroesophageal reflux disease.
AB  - BACKGROUND: Chronic allograft dysfunction limits the long-term success of lung
      transplantation. Increasing evidence suggests nonimmune mediated injury such as
      due to reflux contributes to the development of bronchiolitis obliterans
      syndrome. We have previously demonstrated that fundoplication can reverse
      bronchiolitis obliterans syndrome in some lung transplant recipients with reflux.
      We hypothesized that treatment of reflux with early fundoplication would prevent
      bronchiolitis obliterans syndrome and improve survival. METHODS: A retrospective
      analysis of 457 patients who underwent lung transplantation from April 1992
      through July 2003 was conducted. Patients were stratified into four groups: no
      history of reflux, history of reflux, history of reflux and early (< 90 days)
      fundoplication and history of reflux and late fundoplication. RESULTS: Incidence
      of postoperative reflux was 76% (127 of 167 patients) in pH confirmed subgroups.
      In 14 patients with early fundoplication, actuarial survival was 100% at 1 and 3
      years when compared with those with reflux and no intervention (92% +/- 3.3, 76%
      +/- 5.8; p < 0.02). Further, those who underwent early fundoplication had
      improved freedom from bronchiolitis obliterans syndrome at 1 and 3 years (100%,
      100%) when compared with no fundoplication in patients with reflux (96% +/- 2.5,
      60% +/- 7.5; p < 0.01). CONCLUSIONS: Reflux is a frequent medical complication
      after lung transplantation. Although the number of patients undergoing early
      fundoplication is small, our results suggest early aggressive surgical treatment
      of reflux results in improved rates of bronchiolitis obliterans syndrome and
      survival. Further research into the mechanisms and treatment of nonalloimmune
      mediated lung allograft injury is needed to reduce rates of chronic lung failure.

PMID- 15464463
TI  - Utility of PET, CT, and EUS to identify pathologic responders in esophageal
      cancer.
AB  - BACKGROUND: This study evaluates the utility of positron emission tomography
      (PET), endoscopic ultrasonography (EUS), and computed tomographic (CT) scans to
      predict pathologic response and survival following preoperative chemoradiation
      (CRT) in esophageal cancer. METHODS: One hundred three sequential patients with
      locoregionally advanced esophageal cancer, who were treated with CRT and
      esophageal resection between May 2001 and November 2003 at the University of
      Texas M.D. Anderson Cancer Center, were retrospectively reviewed. PET, EUS, and
      CT were performed before (pre) or after (post) CRT and before surgical resection.
      PET standardized uptake value (SUV) was defined as maximal uptake in primary
      tumor. RESULTS: Most patients were male (91 [88%]) with adenocarcinoma (90
      [87%]). Pretreatment clinical stages were: IIA (42 [41%]), IIB (5 [5%]), III (50
      [49%]), and IVA (6 [6%]). At the time of surgery, 58 patients (56%) had a
      pathologic response to CRT (< or =10% viable cells). Post-CRT measurements that
      correlated with pathologic response were: CT esophageal wall thickness (13.3 vs
      15.3 mm, p = 0.04), EUS mass size (0.7 vs 1.7 cm, p = 0.01) and PET SUV (3.1 vs
      5.8, p = 0.01). Post-CRT PET SUV equal to or greater than 4 had the highest
      accuracy for pathologic response (76%). Univariate and multivariate Cox
      regression analysis demonstrated that a post-CRT PET SUV equal to or greater than
      4 was an independent predictor of survival (HR, 3.5, p = 0.04). CONCLUSIONS: The
      FDG-PET SUV is the most accurate noninvasive test to predict long-term survival
      after preoperative CRT and before surgical resection. Post-CRT FDG-PET cannot,
      however, rule out residual microscopic disease so esophagectomy should remain a
      therapeutic option even if the post-CRT imaging modalities are normal.

PMID- 15464464
TI  - The prognostic importance of immunohistochemically detected node metastases in
      resected esophageal adenocarcinoma.
AB  - BACKGROUND: The number or ratio of lymph node metastases detected by hematoxylin
      & eosin (H&E) staining is the most important predictor of survival in esophageal
      cancer. The survival effect of lymph node metastases detected on
      immunohistochemistry (IHC) is controversial. My colleagues and I hypothesized
      that the extent of nodal disease determined by both H&E and IHC examination would
      more accurately predict survival than either technique alone. METHODS: The study
      population consisted of 37 patients who underwent en bloc esophagectomy as
      primary therapy for esophageal adenocarcinoma 5 or more years ago. All had
      mediastinal and upper abdominal lymphadenectomy. No patient received neoadjuvant
      or adjuvant therapy. Tissue blocks were sectioned for H&E staining to confirm the
      initial histology, and a second slide was stained with monoclonal antibodies AE1
      and CAM 5.2, which are directed at a number of cytokeratin antigens. The slides
      were reviewed by an investigator blinded to clinical outcome. The effect of IHC
      staining on prognosis was assessed by comparing 5-year survival based on H&E and
      IHC findings. RESULTS: A total of 1,970 nodes were examined in the 37 patients.
      Routine H&E staining detected metastases in 29 patients (78%); the remaining 8
      with N0 disease all survived at least 5 years after operation (median not
      reached). In the 29 patients with N1 disease, survival was 41% at 5 years. In 20
      of the 29 N1 patients, metastases were detected by H&E in less than 10% of the
      nodes removed; 55% of the patients survived 5 years, and 39% survived 8 years.
      Nine of the 29 patients had metastases detected in more than 10% of the nodes
      removed, and all died at a median of 17 months. IHC staining was performed on the
      nodes from the 8 N0 patients and the 20 patients with less than 10% nodal
      involvement (a total of 28 patients). Additional nodal metastases, not identified
      on H&E examination, were found in 51 nodes from 17 patients (60.7%). Of the 8
      patients who were node negative on H&E examination, 3 had metastases detected by
      IHC, and all survived 5 years or more free of disease. Of the 20 patients with
      less than 10% nodal metastases on H&E, 14 (70%) had additional metastases
      detected by IHC (median, 2 nodes per patient). When combined with the results of
      H&E staining, the node ratio remained less than 10% in 13 patients and exceeded
      10% in 7. Survival in patients whose ratio remained less than 10% was
      significantly better than in those whose ratio exceeded 10% (actual 5-year
      survival, 77% vs 14%; chi2 = 4.662; p = 0.03). CONCLUSIONS: IHC staining
      techniques can identify nodal metastases missed by routine H&E examination in a
      large number of patients. The combination of H&E and IHC examination is useful in
      patients with less than 10% nodal involvement by H&E examination in that IHC
      detection of micrometastases allows classification into low-risk (> 75% survival)
      and high-risk (< 15% survival) groups. IHC-detected micrometastases are not of
      prognostic importance in N0 patients or those with greater than 10% nodal
      metastases on H&E.

PMID- 15464465
TI  - Reducing hospital morbidity and mortality following esophagectomy.
AB  - BACKGROUND: Esophagogastrectomy (EG) is a formidable operation with significant
      morbidity and mortality rates. Risk factor analyses have been performed, but few
      studies have produced strategies that have improved operative results. This study
      was performed in order to identify prognostic variables that might be used to
      develop a strategy for optimizing outcomes after EG. METHODS: The records of all
      patients (n = 379) who underwent EG patients at a tertiary medical center between
      1996 and 2002 were retrospectively reviewed. Thirty-day morbidity and mortality
      were determined, and multivariable logistical regression analysis assessed the
      effect of preoperative and postoperative variables on early mortality. RESULTS:
      Operations included Ivor Lewis (n = 179), transhiatal (n = 130), and other
      approaches (n = 70). Operative mortality was 5.8%; 64% experienced complications,
      including respiratory complications (28.5%), anastamotic strictures (25%), and
      leak (14%). Increasing age, anastomotic leak, Charlson comorbidity index 3, worse
      swallowing scores, and pneumonia were associated with increased risk of mortality
      by univariate analysis. However, only age (p = 0.002) and pneumonia (p = 0.0008)
      were independently associated with mortality by multivariable analysis. Pneumonia
      was associated with a 20% incidence of death. Patients with pneumonia had
      significantly worse deglutition and anastomotic integrity on barium esophagogram
      compared with patients without pneumonia (p < 0.001, Mann-Whitney rank sum test).
      CONCLUSIONS: Morbidity and mortality of EG are significant, but most
      complications, including anastomotic leak, are not independent predictors of
      mortality. The most important complication after EG is pneumonia. Strategies to
      decrease postoperative mortality should include careful assessment of swallowing
      abnormalities and predisposition to aspiration by cineradiography or fiberoptic
      endoscopy. After EG, acceptable pharyngeal function and airway protection should
      be verified before resuming oral intake.

PMID- 15464466
TI  - Factors affecting postoperative course and survival after en bloc resection for
      esophageal carcinoma.
AB  - BACKGROUND: To identify factors affecting postoperative course and survival after
      esophagectomy for cancer and reasons for improved survival over time. METHODS:
      Complete esophageal resection was attempted for middle and lower third esophageal
      carcinomas in 386 consecutive patients between January 1982 and January 2002. Two
      study periods were analyzed: 1982 to 1993 and 1994 to 2002. Prognostic factors
      were identified by multivariate analysis and the two periods compared. RESULTS:
      Hospital mortality rate decreased from 5.4% to 2.9% (p = 0.245). Both anastomotic
      leakage and pulmonary complications rates decreased from 9.8% to 2.2% (p = 0.001)
      and 24.1% to 19.3% (p = 0.295), respectively. An increased proportion of patients
      had R0 resection in the latter period, 78.5% versus 67.0%, (p = 0.028). Five-year
      survival rate after R0 resection increased from 29% to 46% (p = 0.001), with a
      decreased recurrence rate from 65.8% to 44.3% (p = 0.002). Three favorable
      prognostic factors were identified: low pT stage, pN0 stage, and operation during
      the 1994 to 2002 study period. CONCLUSIONS: Short-term outcome and survival of
      patients with resected esophageal cancer have improved over time. Advances in
      perioperative technique, staging methods, and surgical management combined with
      higher patient selection and use of neoadjuvant chemoradiation may be responsible
      for this progress.

PMID- 15464467
TI  - Combined resection of superior vena cava for lung carcinoma: prognostic
      significance of patterns of superior vena cava invasion.
AB  - BACKGROUND: Combined resection of the superior vena cava (SVC) for lung carcinoma
      remains challenging in terms of technical aspect and prognosis. We attempted to
      clarify the surgical outcome of combined resection and reconstruction of the SVC
      for lung carcinoma. METHODS: Between March 1980 and May 2001, among 3,499 lung
      resections, 40 (1.1%) patients underwent combined resection of the SVC. Thirty
      four were men and 6 were women. Ages ranged from 37 to 77 years, with median of
      64 years. Lobectomy and pneumonectomy was performed in 19 and 21 patients,
      respectively. The SVC system was totally resected and reconstructed with grafts
      in 11 patients, and partially resected in 29 patients. For the latter patients,
      autologous pericardial patches were used in 8 patients, and a running direct
      suture was performed in 21 patients. The survival curves were constructed by the
      method of Kaplan-Meier, and the curves were compared using the log-rank test.
      RESULTS: Thirty-day mortality was 10%. The 5-year survival rate was 24%, with the
      median follow-up period for living patients 67 months (actual 5-year survivors
      were 7). The prognoses were compared between patients with SVC invasion by
      metastatic nodes (n = 15) and those with SVC invasion by a direct tumor extension
      (n = 25), and the survival difference was statistically significant (5-year
      survival rate, 6.6% versus 36%; p = 0.05). CONCLUSIONS: The pattern of SVC
      invasion was considered to be a significant prognostic factor, and this factor
      should be taken into consideration for evaluating the outcome of clinical trials
      for T4 lung cancer.

PMID- 15464468
TI  - Imprint cytology for detecting metastasis of lung cancer in mediastinal lymph
      nodes.
AB  - BACKGROUND: Lymph node metastasis of lung cancer has been evaluated with
      histologic examination. We studied the usefulness of cytologic diagnosis for
      detecting metastasis of lung cancer in mediastinal nodes. METHODS: Five hundred
      twelve stations of mediastinal nodes in 157 patients with lung cancer were
      excised for staging of the disease through mediastinoscopy or thoracoscopy. Among
      them, 474 stations of mediastinal nodes in 151 patients were examined for
      metastasis both with imprint cytology and with hematoxylin-eosin histology
      independently. The final diagnostic decision was made by overall pathologic
      information, including cytology and histology. The diagnostic accuracies were
      compared between cytologic and histologic examinations. RESULTS: Cytologic
      examination identified 66 positive stations and 2 suspicious stations in 45
      patients, whereas histologic examination identified 61 positive stations in 42
      patients. The final pathologic diagnosis was 70 positive stations and 1
      suspicious station in 45 patients. The sensitivity, accuracy, and negative
      predictive value of cytologic examination for node metastasis were 95.7%, 99.4%,
      and 99.3%, respectively, and those of histologic examination were 87.1%, 98.1%,
      and 97.7%, respectively. On a patient basis the sensitivity, accuracy, and
      negative predictive value of cytologic examination were 100%, 100%, and 100%,
      respectively, whereas those of histologic examination were 93.8%, 98.0%, and
      97.2%, respectively. An additional 3 patients (2.0%) who had contralateral
      mediastinal node metastasis diagnosed only with cytology were identified with
      upstaged disease. CONCLUSIONS: Imprint cytology for detecting metastasis of lung
      cancer in mediastinal nodes has high sensitivity and accuracy and is no less
      useful than histologic examination.

PMID- 15464469
TI  - Surgical treatments for multiple primary adenocarcinoma of the lung.
AB  - BACKGROUND: The aim of this study was to identify the clinical characteristics of
      multiple primary adenocarcinomas and to evaluate the efficacy of surgical
      treatments. METHODS: Three-hundred sixty-nine patients who underwent pulmonary
      resection for adenocarcinoma from January 1994 to December 2002 were reviewed.
      RESULTS: Thirty-one patients (8.4%) were determined to have multiple primary
      adenocarcinomas that could be detected on chest x-rays or computed tomography
      (CT). Twenty-six patients were synchronous and five patients were metachronous
      with a median interval of 59.0 months. Forty-nine (72.1%) of the total 68 lesions
      exhibited ground-glass opacity on high-resolution CT (HRCT). Pathologically well
      differentiated adenocarcinoma with mixed bronchioloalveolar pattern was the most
      common subtype (39.7%). Taking into consideration pulmonary function, size,
      location, and HRCT findings of the lesions the procedures performed were
      lobectomy with mediastinal lymph-node dissection for 32 patients, segmentectomy
      with hilar node dissection for 8 patients, and wedge resection for 28 patients.
      Of 17 patients with bilateral synchronous cancers, simultaneous bilateral
      pulmonary resection was performed in 14 patients including simultaneous bilateral
      video-assisted thoracic surgery (VATS) in 11 patients. After a median follow-up
      period of 27.7 months, the 3-year overall survival rate was 92.9% and the 3-year
      disease-free survival rates of synchronous cancer and metachronous cancer were
      77.9% and 100%, respectively. CONCLUSIONS: The incidence of multiple primary
      adenocarcinomas was relatively common. Early radiographic detection and surgical
      excision could yield a favorable prognosis. The use of VATS, even for synchronous
      bilateral patients, was a safe and beneficial procedure.

PMID- 15464470
TI  - Pulmonary resection after curative intent radiotherapy (>59 Gy) and concurrent
      chemotherapy in non-small-cell lung cancer.
AB  - BACKGROUND: Pulmonary resection after chemotherapy and concurrent full-dose
      radiotherapy (>59 Gy) has previously been associated with unacceptably high
      morbidity and mortality. Subsequently neoadjuvant therapy protocols have used
      reduced and potentially suboptimal radiotherapy doses of 45 Gy. We report a
      series of 40 patients with locally advanced non-small-cell lung cancer who
      successfully underwent pulmonary resection after receiving greater than 59 Gy
      radiation and concurrent chemotherapy. Operative results and midterm survival
      follow-up are presented. METHODS: Data were reviewed from 40 consecutive patients
      who underwent lung resection after receiving high-dose radiotherapy and
      concurrent platinum-based chemotherapy between January 1994 and May 2000. The
      follow-up closing interval for this study was until August 2003 or time of death.
      RESULTS: Preoperative stage was IIb (7 patients), IIIA (21 patients), IIIB (10
      patients), and IV (2 patients with isolated brain metastasis). Thirteen patients
      exhibited Pancoast tumors. Median time from completion of induction therapy to
      surgery was 53 days. Twenty-nine lobectomies and 11 pneumonectomies (7 right, 4
      left) were performed. There were no postoperative deaths. Intercostal muscle
      flaps were used prophylactically in all but one pneumonectomy patient. Seven
      patients required perioperative transfusions. Median intensive care unit (ICU)
      time averaged 2 days and the total length of stay was 6 days. One patient
      exhibited postpneumonectomy pulmonary edema and a bronchopleural fistula
      developed in another patient (not receiving an intercostal muscle flap). Thirty
      four of 40 patients (85%; 95% CI: 70%-94%) were downstaged pathologically, 33 out
      of 40 patients (82.5%, 95% confidence interval [CI]: 67%-93%) indicated no
      residual lymphadenopathy, and 18 out of 40 patients (45%, 95% CI: 29%-61%)
      exhibited a complete pathologic response. Median follow-up was 2.8 years. The 1-,
      2-, and 5-year overall survival rates were 92.4%, 66.7%, and 46.2%, respectively.
      Disease-free 1-, 2-, and 5-year survival rates were 73.0%, 67.2%, and 56.4%,
      respectively. Median disease-free survival has not been reached. CONCLUSIONS:
      Pulmonary resection may be performed safely after curative intent concurrent
      chemotherapy and radiotherapy to greater than 59 Gy. High pathologic complete
      response rates and sterilization of mediastinal lymph nodes were observed
      accompanied by highly favorable survival rates. This experience, though
      promising, will require confirmation in a prospective multiinstitutional clinical
      trial.

PMID- 15464472
TI  - Proteasome inhibition sensitizes non-small-cell lung cancer to gemcitabine
      induced apoptosis.
AB  - BACKGROUND: My colleagues and I have previously shown that chemotherapy activates
      the antiapoptotic transcription factor nuclear factor (NF)-kappaB in non-small
      cell lung cancer (NSCLC). We hypothesized that inhibition of NF-kappaB by using
      the proteasome inhibitor bortezomib (Velcade) would sensitize NSCLC to
      gemcitabine-induced apoptosis. METHODS: Tumorigenic NSCLC cell lines (H157 and
      A549) were treated with nothing, gemcitabine, bortezomib, or both compounds. NF
      kappaB activity was determined by nuclear p65 protein levels, electrophoretic
      mobility shift assays, and reverse transcription-polymerase chain reaction of the
      NF-kappaB-regulated genes interleukin-8, c-IAP2, and Bcl-xL. The p21 and p53
      protein levels were determined in similarly treated cells. Cell-cycle
      dysregulation was assessed by fluorescence-activated cell sorting analysis. Cell
      death and apoptosis were quantified by clonogenic assays, caspase-3 activation,
      and DNA fragmentation. NSCLC A549 xenografts were generated and treated as noted
      previously. Tumor growth was assessed over a 4-week treatment period. Statistical
      analysis was performed with analysis of variance. RESULTS: Gemcitabine enhanced
      nuclear p65 levels, NF-kappaB binding to DNA, and transcription of all NF-kappaB
      regulated genes. Bortezomib inhibited each of these effects. Combined gemcitabine
      and bortezomib enhanced p21 and p53 expression and induced S-phase and G2/M cell
      cycle arrests, respectively. Combined treatment killed 80% of the NSCLC cells and
      induced apoptosis, as determined by caspase-3 activation (p = 0.05) and DNA
      fragmentation (p = 0.02). NSCLC xenografts treated with combination therapy grew
      significantly slower than xenografts treated with gemcitabine alone (p = 0.02).
      CONCLUSIONS: Bortezomib inhibits gemcitabine-induced activation of NF-kappaB and
      sensitizes NSCLC to death in vitro and in vivo. This combined treatment strategy
      warrants further investigation and may represent a reasonable treatment strategy
      for select patients with NSCLC given the current clinical availability of both
      drugs.

PMID- 15464473
TI  - Use of quantitative lung scintigraphy to predict postoperative pulmonary function
      in lung cancer patients undergoing lobectomy.
AB  - BACKGROUND: In patients with non-small cell lung cancer, the only realistic
      chance of cure is surgical resection. However, in some of these patients there is
      such poor respiratory reserve that surgery can result in an unacceptable quality
      of life. In order to identify these patients, various pulmonary function tests
      and scintigraphic techniques have been used. The current American College of
      Physicians and British Thoracic Society guidelines do not recommend the use of
      quantitative ventilation-perfusion scintigraphy to predict postoperative function
      in lung cancer patients undergoing lobectomy. These guidelines may have been
      influenced by previous scintigraphic studies performed over a decade ago. Since
      then there have been advances in both surgical techniques and scintigraphic
      techniques, and the surgical population has become older and more female
      represented. METHODS: We prospectively performed spirometry and quantitative
      ventilation-perfusion scintigraphy on 61 consecutive patients undergoing
      lobectomy for lung cancer. Spirometry was repeated one-month postsurgery. Both a
      simple segment counting technique alone and scintigraphy were used to predict the
      postoperative lung function. RESULTS: There was statistically significant
      correlation (p < 0.01) between the predicted postoperative lung function using
      both the simple segment counting technique and the scintigraphic techniques.
      However, the correlation using simple segment counting was of negligible
      difference compared to scintigraphy. CONCLUSIONS: In keeping with current
      American Chest Physician and British Thoracic Society guidelines, our results
      suggest that quantitative ventilation-perfusion scintigraphy is not necessary in
      the preoperative assessment of lung cancer patients undergoing lobectomy. The
      simple segmenting technique can be used to predict postoperative lung function in
      lobectomy patients.

PMID- 15464474
TI  - Chest-wall desmoid tumors: results of surgical intervention.
AB  - BACKGROUND: We are analyzing our experience with treatment of desmoid tumors of
      the chest wall and adjacent structures. METHODS: A retrospective review was
      undertaken of the records of all patients who underwent surgical management for a
      desmoid tumor of the chest between January 1980 and December 2001 at one
      institution. Fifty-three patients (24 men and 29 women) were identified, whose
      median age was 39 years (range 10 to 78 years). RESULTS: The desmoid tumor
      involved the chest wall exclusively in 25 patients (47%) and both the chest wall
      and adjacent structures in 28 (53%). Twenty-eight patients (53%) had previous
      resections for a desmoid tumor. Three patients also had previous radiation
      therapy. A wide radical resection was attempted in all 53 patients; resection was
      complete in 44. Seven patients had positive microscopic margins and 2 had gross
      residual disease. Complications were noted in 6 patients (11%); no operative
      deaths occurred. Median hospitalization was 6 days (range 1 to 124 days).
      Nineteen patients (36%) had postoperative radiation therapy (12 had complete
      resection and 7 had positive margins). Follow-up was complete in 51 patients
      (96%) and ranged from 2 weeks to 21 years (median 53 months). At the end of the
      review 46 patients were alive with no recurrence; 3 were alive with local
      recurrence and 2 died (1 from metastatic breast cancer and 1 from unknown cause).
      Five-year overall probability of developing a local recurrence was 37.5% (95%
      confidence interval, 20.2% to 53.3%). Recurrence occurred in 8 of 9 patients with
      positive margins (89%) and 8 of 44 with negative margins (18%). Factors adversely
      affecting the rate of postoperative recurrence were reoperation (p = 0.0199),
      positive margins (p < 0.0001), and postoperative radiation therapy (p = 0.0027).
      Eleven patients (22%) required reoperation at a median of 24.6 months
      postoperatively (range 11 to 78 months). CONCLUSIONS: Desmoid tumors involving
      the chest and adjacent structures are locally aggressive tumors with a high
      recurrence rate. Wide radical resection should be attempted whenever possible.
      Positive margins at resection, reoperation and postoperative radiation are
      associated with a high risk of local recurrence.

PMID- 15464475
TI  - Short- and long-term outcomes after large pulmonary resection for germ cell
      tumors after bleomycin-combination chemotherapy.
AB  - BACKGROUND: Treatment of nonseminomatous germ cell tumors frequently requires
      bleomycin-combination chemotherapy followed by resection of residual disease.
      Bleomycin administration however raises concerns with respect to postoperative
      respiratory complications, particularly for patients undergoing large pulmonary
      resections. We undertook an institutional review to determine the outcome of
      large pulmonary resections after bleomycin-combination chemotherapy. METHODS:
      Between 1981 and 2001, 530 patients presented to our institution for resection of
      residual intrathoracic disease for either metastatic testicular or primary
      mediastinal nonseminomatous germ cell tumors. We subsequently reviewed 32 of
      these patients who required pneumonectomy (n = 19; RIGHT = 9, LEFT = 10) or
      bilobectomy (n = 13) after bleomycin-combination chemotherapy. RESULTS: There
      were four operative deaths (13%). All postoperative deaths occurred in patients
      undergoing right-sided resections (pneumonectomy, n = 2; bilobectomy, n = 2) as a
      consequence of pulmonary complications. Operative survivors had a pulmonary
      morbidity of 18%. Fourteen of 20 long-term survivors were found to have a
      satisfactory performance status at follow-up. CONCLUSIONS: Otherwise young and
      healthy male nonseminomatous germ cell tumors patients requiring large pulmonary
      resections after bleomycin-combination chemotherapy appear to be at higher than
      anticipated risk for pulmonary-related morbidity and mortality. However long-term
      survivors report an acceptable functional status.

PMID- 15464477
TI  - Extracorporeal membrane oxygenation after lung transplantation: evolving
      technique improves outcomes.
AB  - BACKGROUND: Severe pulmonary graft failure (PGF) is the most common cause of
      death within the first 30 days after lung transplantation. Extracorporeal
      membrane oxygenation (ECMO) may provide lifesaving temporary support; however,
      its longer-term efficacy is controversial. METHODS: We reviewed the use of ECMO
      for severe PGF after lung transplantation, and compared the outcomes between our
      early (1990 to 1999) and recent (2000 to 2003) experience utilizing improved
      initiation timing, oxygenator technology, and surgical technique. RESULTS: Ten
      transplant recipients from a total of 481 (2.1%) were managed for PGF on ECMO by
      a multidisciplinary team at The Alfred Hospital. Four single-lung, 3 bilateral
      single-lung, and 3 heart-lung recipients were supported for a mean of 96 hours
      (range 14 to 212 hours). In the early group (operation from 1990 to 1999, n = 4)
      ECMO was initiated 21 days (range 7 to 40 days) after lung transplantation and in
      the recent group (operation from 2000 to 2003, n = 6) after 0 to 2 days (p =
      0.01). Radial-arterial blood gas analysis 12 hours after initiation of ECMO
      showed significantly better oxygenation in the recent group (341 +/- 90 mm Hg)
      than in the early group (90 +/- 23 mm Hg, p = 0.03). Four deaths occurred as a
      result of bleeding (two in each group). In the early group only 1 patient was
      weaned from ECMO but died. In the recent group 3 were successfully weaned and
      were discharged from the intensive care unit; of these patients, 2 were
      discharged from hospital. CONCLUSIONS: Extracorporeal membrane oxygenation
      results have improved with advances in oxygenator technology and surgical
      techniques. The procedure can allow resolution of early PGF after lung
      transplantation.

PMID- 15464478
TI  - Training residents in mitral valve surgery.
AB  - BACKGROUND: The safety of training residents in complex procedures has not been
      elucidated. In particular, the impact of resident-performed mitral valve surgery
      on patient outcomes is unknown. METHODS: All mitral valve procedures performed by
      residents between 1998 and 2003 were compared with those performed by staff
      surgeons. Operative mortality and a composite morbidity (reoperation for
      bleeding, myocardial infarction, infection, stroke, or ventilation > 24 hours)
      were compared using multivariate analysis. Individual outcomes were compared with
      the use of propensity scores. RESULTS: There were 1020 cardiac surgeries
      performed by residents, including 165 mitral valve procedures (86 replacements,
      79 repairs). In the same period, the staff surgeons performed 261 mitral
      procedures. Crude operative mortality for isolated mitral procedures was 5.4% and
      4.7% (resident and staff, respectively, p = 1.00). Mitral valve repair including
      combined procedures had an operative mortality of 3.8% and 4.3% (resident and
      staff, respectively, p = 1.00). The composite morbidity outcome was 29.7% and
      35.3% for resident and staff-performed cases, respectively (p = 0.24). In
      multivariate analysis, resident was not associated with the adverse outcomes
      examined (OR 0.80, 95% CI, 0.47, 1.37). The incidence of major adverse outcomes
      for propensity score-matched mitral valve cases, including combined procedures,
      were similar between residents and staff, respectively: mortality, 7.4% versus
      8.7% (p = 0.67), stroke, 4.0% versus 6.7% (p = 0.30), and reoperation for
      bleeding, 4.7% versus 9.4% (p = 0.11). CONCLUSIONS: There were no significant
      differences in morbidity and mortality in patients undergoing mitral valve
      surgery between resident and staff surgeons. It is possible to train residents to
      perform complex cardiac cases without adversely affecting outcomes.

PMID- 15464479
TI  - Survival after mitral valve replacement: rationale for surgery before occurrence
      of severe symptoms.
AB  - BACKGROUND: This study was undertaken to evaluate survival after mitral valve
      replacement, with a focus on the impact of age and preoperative symptoms.
      METHODS: Survival was analyzed in 784 patients undergoing mitral valve
      replacement from 1980 through 2000. Relative survival was estimated by relating
      the observed survival to the expected survival in a cohort, comparable regarding
      sex, age group, and calendar period, in the general Swedish population. RESULTS:
      Early mortality was 9.7%. Relative survival rates after 5, 10, and 15 years were
      83%, 70%, and 54%, respectively. The corresponding rates for observed survival
      were 75%, 56%, and 36%. Advanced New York Heart Association class, but not high
      age, was a risk factor for early mortality, whereas both factors decreased
      survival. An association between age and New York Heart Association class was
      found, the majority of old patients also being severely symptomatic. Patients in
      New York Heart Association classes I and II showed excellent relative survival.
      CONCLUSIONS: Survival is reduced after mitral valve replacement in patients with
      severe preoperative symptoms, whereas patients with less-severe symptoms show
      excellent survival. Older patients were more often severely symptomatic at the
      time of surgery. Irrespective of age, surgery before the occurrence of advanced
      symptoms should improve the long-term outcome.

PMID- 15464480
TI  - The dynamic anterior mitral annulus.
AB  - BACKGROUND: The anterior mitral annulus is considered a fixed structure. Recent
      data suggest otherwise. This study tested the hypothesis that the size of the
      anterior annulus varies with hemodynamic loading and ventricular contractility.
      METHODS: Sonomicrometry array localization measured annular area, total annular
      circumference, anterior circumference, and posterior circumference in 6 sheep
      before and after neosynephrine increased systolic blood pressure by at least 150%
      during atrial pacing at 120 beats/min. In 6 additional animals the same
      dimensions were measured during atrial pacing (at 120 and 150 beats/min) and
      during isoproteronol infusions to increase heart rate to 120 and 150 beats/min.
      RESULTS: Neosynephrine increased systolic total annular circumference from 99.7
      +/- 5.5 mm to 106.9 +/- 9.6 mm. Anterior circumference increased from 40.8 +/-
      4.0 mm to 45.3 +/- 5.7 mm whereas posterior circumference only increased from
      59.0 +/- 5.5 mm to 61.6 +/- 7.0 mm. Low isoproteronol infusion decreased systolic
      total annular circumference from 107.5 +/- 8.3 mm to 101.9 +/- 10.6 mm. Most of
      this change occurred in the posterior circumference. Higher infusions of
      isoproteronol decreased total annular circumference from 106.8 +/- 8.3 mm to 98.3
      +/- 9.7 mm. At this higher inotropic state the decrease in annular size was
      similar in the anterior and posterior annulus. CONCLUSIONS: In sheep, the
      anterior annulus is a dynamic structure that varies in size in response to
      changes in hemodynamic loading and ventricular contractility.

PMID- 15464481
TI  - Initial results after combined repair of aortic arch aneurysms by sequential
      transposition of the supra-aortic branches and consecutive endovascular stent
      graft placement.
AB  - BACKGROUND: To evaluate safety and efficacy of a combined repair of aortic arch
      aneurysms by sequential transposition of the supra-aortic branches and
      endovascular stent-graft placement. METHODS: Between October 2002 and September
      2003, 5 patients (mean age, 79.5 years) presented with aortic arch aneurysms
      involving the origin of the left carotid artery. Treatment was made by sequential
      transposition of the left carotid artery into the brachiocephalic trunk and
      transposition of the left subclavian artery into the already transposed left
      common carotid artery with consecutive endovascular stent-graft placement into
      the aortic arch. RESULTS: All patients survived both procedures. At completion
      angiography, a small type 1a endoleak was observed in 1 patient. After 1 week,
      the patient was readmitted for completion three-dimensional computed tomographic
      scan. The leak had already occluded spontaneously. Mean follow-up was 10 months
      (range, 4 to 16 months). At follow-up, all patients had normal computed
      tomographic scans with regular perfusion of the supra-aortic branches without any
      signs of endoleaks. CONCLUSIONS: Combined repair of aortic arch aneurysms by
      sequential transposition of the supra-aortic branches with consecutive
      endovascular stent-graft placement is feasible. Extended application of this
      technique will enable safe and effective treatment of a highly selected subgroup
      of patients with aortic aneurysms by avoiding conventional arch aneurysm repair
      in deep hypothermia and circulatory arrest.

PMID- 15464482
TI  - Emergency endovascular stent-grafting for life-threatening acute type B aortic
      dissections.
AB  - BACKGROUND: There is still a considerable controversy regarding optimal treatment
      for patients with acute type B aortic dissection. Patients with complicated
      disease are particularly challenging for cardiovascular treatment. Early surgery
      for acute dissections of the descending aorta with life-threatening complications
      is known to carry a high mortality. Endovascular stent grafting is developing as
      an alternative treatment mainly for chronic stages of type B aortic dissection.
      It is not clear whether endovascular stent grafting is safe and effective in
      emergency treatment of acute type B aortic dissection. METHODS: In 10 patients (7
      men, 3 women; mean age, 59.2 years; range, 46 to 65 years), endovascular stent
      grafting was performed within 11.0 +/- 5.9 hours (range, 4 to 24 hours) of
      diagnosis of complications. Indications for acute intervention included contained
      rupture, hematothorax, life-threatening malperfusion, and refractory pain. Using
      a retrograde endovascular route after surgical exposure of the femoral artery,
      self-expanding stent prostheses consisting of polyester-covered Nitinol (Talent,
      World Medical; mean diameter, 40 +/- 4 mm; length, 10 cm) were placed into the
      descending aorta distal to the subclavian artery. Before discharge and on follow
      up visits, imaging of the aorta was performed using computed tomography. RESULTS:
      In 9 of 10 patients (90%), the primary entry could be completely occluded with
      the endovascular stent. Early mortality was 20% (2 of 10): 1 patient died after
      disruption of the intimal layer distal to the stent, and 1 patient died in
      hemorrhagic shock after surgical fenestration of the abdominal aorta for
      persistent malperfusion. Three patients (30%) required consecutive surgical
      treatment: indications included acute development of retrograde type A aortic
      dissection, acute stent dislocation by fractured wires and secondary leakage, and
      late formation of an aneurysm of the descending aorta 6 months after endovascular
      stent grafting. There were no surgical or late deaths. CONCLUSIONS: Our
      experience provides some evidence that early mortality of life-threatening acute
      type B aortic dissection may be reduced by emergency endovascular stent grafting
      and that this form of treatment is a promising therapeutic option. Refinements,
      especially in stent design and application, may further improve the prognosis of
      patients in the life-threatening situation of complicated acute type B aortic
      dissection.

PMID- 15464484
TI  - Long-term outcome and prognostic predictors of medically treated acute type B
      aortic dissections.
AB  - BACKGROUND: The purpose of this study was to examine the long-term outcome and
      the prognostic predictors related to the development of complications associated
      with acute type B aortic dissection. METHODS: Seventy-six medically treated
      patients with acute type B aortic dissection were examined between 1990 and 2001.
      The events associated with aortic dissection included dissection-related death,
      rupture, visceral ischemia, lower limb ischemia, an increase in the maximum
      aortic diameter greater than 50 mm, and a mean enlargement rate of greater than 5
      mm per year. RESULTS: Among the 76 patients 10 (13%) underwent chronic phase
      surgery and 25 (33%) presented with an event. A statistically significant
      difference was observed between patients with and without events with regard to
      atherosclerotic factors, blood flow status in the false lumen, maximum aortic
      diameter upon admission, mean aortic enlargement rate, and blood pressure control
      during follow-up. Of these factors a patent false-lumen and a maximum aortic
      diameter greater than 40 mm upon admission were the most strongly associated
      factors with regard to the development of events. Patients with a patent false
      lumen and a maximum aortic diameter greater than 40 mm upon admission were
      determined to exhibit significantly higher event rates than other patients.
      CONCLUSIONS: In determining the appropriate therapeutic approach for acute type B
      aortic dissection, it is important to pay careful attention to the predictors of
      a patent false-lumen and a maximum aortic diameter greater than 40 mm at onset to
      improve the long-term outcome.

PMID- 15464485
TI  - Does the arterial cannulation site for circulatory arrest influence stroke risk?
AB  - BACKGROUND: We investigated whether axillary/subclavian artery inflow with a side
      graft decreases the risk of stroke versus cannulation at other sites during
      hypothermic circulatory arrest. METHODS: Between January 1993 and May 2003, 1,352
      operations with circulatory arrest were performed for complex adult cardiac
      problems. A single arterial inflow cannulation site was used in 1,336 operations,
      and these formed the basis for comparative analyses. Cannulation sites were
      axillary plus graft in 299 operations, direct cannulation of the aorta in 471,
      femoral in 375, innominate in 24, and axillary or subclavian without a side graft
      in 167. Retrograde brain perfusion was used in 933 (69%). A total of 272 (20%)
      were for emergencies, 432 (32%) were reoperations, and 439 (32%) were for
      dissections. A total of 617 (46%) had aortic valve replacement and 1,160 (87%)
      ascending, 415 arch (31%), and 248 descending (18%) aortic replacements.
      Indications also included arteriosclerosis (n = 301) and calcified aorta (n =
      278). Primary comparisons were made by using propensity matching, and,
      secondarily, risk factors for stroke or hospital mortality were identified by
      multivariable logistic regression. RESULTS: Stroke occurred in 6.1% of patients
      (81/1,336): 4.0% (12/299) of those had axillary plus graft and 6.7% who had
      direct cannulation (69/1,037; p = 0.09; p = 0.05 among propensity-matched pairs).
      Operative variables associated with stroke included direct aortic cannulation,
      aortic arteriosclerosis, descending aorta repair, and mitral valve replacement.
      The risk of hospital mortality was higher (11%; 42/375) for patients who had
      femoral cannulation than axillary plus graft (7.0%; 21/299; p = 0.06; p = 0.02
      among propensity-matched pairs). CONCLUSIONS: Axillary inflow plus graft reduces
      stroke and is our method of choice for complex cardiac and cardioaortic
      operations that necessitate circulatory arrest. Retrograde or antegrade perfusion
      is used selectively.

PMID- 15464486
TI  - Femoral cannulation is safe for type A dissection repair.
AB  - BACKGROUND: Recently, surgeons have embraced axillary artery cannulation for type
      A aortic dissection repair out of concern for malperfusion phenomena with
      traditional femoral artery cannulation. My colleagues and I sought to determine
      whether these concerns are justified. METHODS: Records of 86 consecutive patients
      (51 men and 35 women; age, 30 to 86 years; mean, 62 years) undergoing surgical
      repair for acute type A dissection were reviewed. Cannulation site, specific
      operative repair, and complications related to cannulation were noted. RESULTS:
      Seventy-nine cannulations were performed in the femoral artery (47 left, 23
      right, and 9 unspecified), 3 in the axillary artery (1 left and 2 right), and 4
      in the ascending aorta or arch. Deep hypothermic arrest was used in 64
      operations. Seven involved re-sternotomy. Seventy patients had supracoronary
      grafts (2 with valve replacement and 10 with valve resuspension), and 16
      underwent aortic root replacement. Fourteen patients were in shock from cardiac
      tamponade. Eighty patients survived the operation, and 71 were hospital
      survivors. Malperfusion on initiation of cardiopulmonary bypass was noted in 3
      patients. In 1, the original cannulation site was the ascending aorta, and the
      cannula was moved to the femoral artery for correction. In 2, the original
      cannulation site was the femoral artery, and the cannula was moved to the
      ascending aorta. Malperfusion on clamping of the aorta or on resumption of aortic
      flow was noted in no patient. Postoperative ischemia of any vascular bed was
      noted locally only in 3 (cannulated) lower extremities. CONCLUSIONS: Straight
      femoral cannulation for all phases of type A dissection repair is appropriate and
      yields excellent clinical results. The anticipated malperfusion events are
      actually rare (2 of 79 with femoral artery cannulation, or 2.5%).

PMID- 15464487
TI  - Flow dynamics of the internal thoracic and radial artery T-graft.
AB  - BACKGROUND: Complex use of arterial conduits has resurrected concerns about the
      adequacy of conduit flow. The T-graft is the extreme example of this trend. Our
      purpose was to identify the limitation of single source inflow and to compare
      flow capacity with completion coronary flow. METHODS: Between February 1999 and
      November 2001, 372 patients underwent total arterial revascularization with the T
      graft alone. Intraoperative flows were recorded for each limb of the T-graft
      before and after distal anastomoses in 204 patients. Independent predictors of T
      graft flow were identified by multivariate analysis. RESULTS: Free flow for the
      radial arterial (RA) limb was 161 +/- 81 mL/min, the internal thoracic artery
      (ITA) limb 137 +/- 57 mL/min (combined 298 +/- 101 mL/min) versus simultaneous
      limb flow of 226 +/- 84 mL/min giving a flow restriction of 24% +/- 14%.
      Completion coronary flow was 88 +/- 49 mL/min for the RA, 60 +/- 45 mL/min for
      the ITA, and 140 +/- 70 mL/min for both limbs simultaneously to give a flow
      reserve (vs simultaneous free flow) of 160% or 1.6. Independent predictors of
      completion RA limb flow are RA proximal diameter (p = 0.005), number of
      anastomoses (p = 0.018), and target stenosis (p = 0.005). CONCLUSIONS: A flow
      reserve of 1.6 compares favorably with an ITA flow reserve of 1.8 at 1-month
      postoperatively and 1.8 for both the ITA T-graft and the ITA/RA T-graft at 1-week
      postoperatively as reported by others. Proximal RA diameter and competitive
      coronary flow influence completion T-graft flow. These data quantitate the
      limitation of single source inflow of the T-graft configuration and support its
      continued use.

PMID- 15464488
TI  - Papaverine delivery to the internal mammary artery pedicle effectively treats
      spasm.
AB  - BACKGROUND: Left internal mammary artery spasm is well recognized during coronary
      artery bypass operations. Papaverine has been used by many surgeons to maximize
      mammary artery flow perioperatively, but the best delivery method is not known.
      We analyzed two techniques used at our institution. METHODS: Fifty-eight patients
      were randomized into three groups to compare papaverine's ability to prevent
      spasm and to treat established spasm. Group 1 was control and no treatment was
      employed. In group 2, papaverine was injected with a blunt needle through the
      endothoracic fascia parallel to the mammary artery before harvest to assess spasm
      prevention. In group 3, papaverine was delivered perivascular in an identical
      manner to group 2 but after the mammary artery was dissected from the chest wall.
      This group was an evaluation of spasm treatment. Drug dosage was the same for
      both groups and routine bypass grafting was performed. Before anastomosing the
      mammary artery to the left anterior descending artery, blood flow was recorded
      for 15 seconds and flow per minute calculated. Cardiopulmonary bypass pressures
      were maintained at 70 mm Hg during collection. RESULTS: Mean blood flows were:
      group 1 = 86.2 mL/min, group 2 = 122.5 mL/min, and group 3 = 139.7 mL/min. Left
      internal mammary artery flow in group 3 was statistically different from control
      (p = 0.0457). Group 2 flow approached but did not reach statistical significance
      (p = 0.0874). Mammary artery dissection times for the three groups were not
      different. CONCLUSIONS: Papaverine delivery to the left internal mammary artery
      after dissection treats spasm effectively, improves blood flow at the time of its
      anastamosis to the left anterior descending artery, and avoids any risk of
      intimal injury. Injection of papaverine before mammary artery harvest does not
      shorten dissection time, and flow is not statistically improved.

PMID- 15464489
TI  - Prostacyclin reduces incidence of myocardial damage after coronary
      endarterectomy.
AB  - BACKGROUND: After coronary endarterectomy, patients have an increased incidence
      of perioperative myocardial infarction. This study was undertaken to evaluate the
      possible reduction of perioperative myocardial damage after coronary
      endarterectomy by intravenous utilization of prostacyclin. METHODS: Elective
      coronary artery bypass grafting was performed in 1,190 patients with diffuse and
      distal coronary artery disease, in whom endarterectomy of one or more vessels was
      used as a treatment. All procedures were done with cardiopulmonary bypass. There
      were 584 patients in the prostacyclin-treated group, and 606 patients in the
      control group. Prostacyclin (10 ng x kg(-1) x min(-1)) was started 20 minutes
      before the cross-clamp removal, or at the time of rewarming, and was continued
      during the first 24 hours after surgery. The incidence of perioperative
      myocardial damage was detected by creatine kinase-MB enzyme measurement, and
      electrocardiographic and left ventricular function changes. RESULTS: A
      significant decrease in perioperative myocardial damage was detected in the group
      treated with prostacyclin with respect to the control group. CONCLUSIONS:
      Prostacyclin infusion initiated during revascularization and continued in the
      early postoperative course could be successfully employed for the prevention of
      thrombocyte aggregation and potentially decrease the overall incidence of
      significant myocardial damage after coronary endarterectomy.

PMID- 15464490
TI  - Total arterial off-pump coronary artery bypass grafting for revascularization of
      the total coronary system: clinical outcome and angiographic evaluation.
AB  - BACKGROUND: We assessed the clinical outcome and conducted an angiographic study
      of total arterial off-pump coronary artery bypass grafting for revascularization
      of the total coronary system. METHODS: Of 382 consecutive patients who underwent
      off-pump coronary artery bypass between April 2000 and December 2002, 235
      patients (193 men and 42 women, mean age 66 +/- 9 years) with three-vessel
      disease underwent off-pump coronary artery bypass with all arterial grafts. A
      total of 872 vessels were bypassed (average number of grafts 3.7 +/- 0.8). The
      internal thoracic arteries, radial arteries, and gastroepiploic arteries were
      used for revascularization of 306, 542, and 24 coronary arteries, respectively.
      Two hundred twenty-five patients underwent revascularization with composite
      grafts that were connected to the in situ internal thoracic artery (Y
      configuration 181, I configuration 55, K configuration 27, X configuration 3, T
      configuration 1); 10 patients underwent revascularization with all in situ
      grafts. RESULTS: Three (1.3%) hospital deaths and 1 late death occurred. There
      were no occurrences of clinical underperfusion syndrome or new intraaortic
      balloon pump insertion. Cerebral infarction occurred in 2 patients (0.8%). Early
      postoperative angiography was performed on 833 grafts in 223 patients (95%); the
      overall patency rate was 98%. Stratified by coronary distribution, the patency
      rate was 99% (218/221) in the left anterior descending artery, 97% (84/87) in the
      diagonal artery, 99% (70/71) in the obtuse marginal artery, 98% (262/268) in the
      posterolateral artery, 98% (167/170) in the posterior descending artery, and 100%
      (16/16) in the right coronary artery. CONCLUSIONS: Total arterial off-pump
      coronary artery bypass yielded good clinical results and an excellent patency
      rate of revascularization for the total coronary system.

PMID- 15464491
TI  - Intimal hyperplasia and expression of transforming growth factor-beta1 in
      saphenous veins and internal mammary arteries before coronary artery surgery.
AB  - BACKGROUND: The development of fibromuscular intimal hyperplasia and subsequent
      graft failure remains an urgent problem in cardiac surgery. Transforming growth
      factor-beta1 (TGF-beta1) is involved in the pathogenesis of arteriosclerosis
      through induction of extracellular matrix proteins. We tested the hypothesis that
      intimal hyperplasia is already present in human saphenous veins and left internal
      mammary arteries before coronary artery bypass surgery and is associated with an
      increased expression of TGF-beta1. METHODS: Forty-six segments of saphenous veins
      and 27 of left internal mammary arteries were collected from 50 patients
      undergoing coronary artery bypass surgery. Morphometric analysis was performed by
      microscopic computer analysis. Immunohistochemistry was performed with antibodies
      directed against TGF-beta1, its latent binding protein (LTBP-1) and its type 2
      receptor (RII). RESULTS: The incidence of intimal hyperplasia was significantly
      higher in saphenous veins (67.4%) than in mammary arteries (29.6%; p < 0.05).
      Saphenous veins and mammary arteries with intimal hyperplasia expressed more TGF
      beta1 (endothelial and intimal layers) and LTBP-1 (intimal and medial layers)
      when compared with corresponding vessels without hyperplasia (both groups p <
      0.05). Endothelial and intimal RII expression was significantly higher in
      saphenous veins with intimal hyperplasia as compared with saphenous veins without
      hyperplasia (p < 0.05). Transforming growth factor-beta1 staining in the intima
      correlated with the presence of an intimal hyperplasia in saphenous veins (rho =
      0.317) and mammary arteries (rho = 0.428). CONCLUSIONS: Local TGF-beta1
      expression is associated with the presence of intimal hyperplasia in the examined
      vessels. Preexisting intimal hyperplasia is more prevalent and serious in
      saphenous veins than in left internal mammary arteries, giving further
      explanation to the superior long-term results of left internal mammary grafts.

PMID- 15464492
TI  - Harvesting techniques affect the integrity of the radial artery: an electron
      microscopic evaluation.
AB  - BACKGROUND: Four methods of radial artery harvesting were evaluated with
      transmission electron microscopy and tissue lipid peroxidation to determine the
      degree of damage to the artery. METHODS: Radial artery samples from 4 groups of
      patients (10 samples from each group) who underwent coronary artery surgery were
      evaluated. In groups I and II, radial arteries were stored in a solution
      containing 100 mL patients' own heparinized oxygenated blood and 5 mg
      nitroglycerine. The grafts were distended in group II. In groups III and IV, side
      branches of the grafts were occluded and left in situ until the coronary
      anastomosis. In group III, the distal end of the graft was also occluded, while
      in group IV, both ends were open. RESULTS: The least degree of endothelial damage
      and disruption of arterial wall integrity were in group IV according to electron
      microscopic evaluation. The grafts in group III were relatively in good condition
      compared to groups I and II. Tissue lipid peroxidation was also lowest in group
      IV. Tissue lipid peroxide levels correlated with ischemic preservation period of
      the radial artery (r = 0.426). Total semiquantitative transmission electron
      microscopic scores of the radial artery samples correlated with the lipid
      peroxide levels (r = 0.581) and ischemia times (r = 0.734). CONCLUSIONS: All
      arterial grafts, including the radial artery that will be used for coronary
      artery surgery should not be left ischemic during harvesting to prevent
      endothelial damage. Ischemia of the conduits for coronary artery grafting can be
      prevented by leaving them in their anatomic position until the distal coronary
      artery anastomosis.

PMID- 15464493
TI  - What is the optimal channel density for transmyocardial laser revascularization?
AB  - BACKGROUND: Transmyocardial laser revascularization (TMR) has demonstrated
      reproducible relief of angina in patients with end-stage coronary disease.
      However, the optimum dose or channel density has not been elucidated. METHODS:
      Using a porcine model of chronic myocardial ischemia, 14 animals were treated
      with CO2 TMR and randomized as follows: group 1 was 1 channel per 2 cm2; group 2
      was 1 channel per 1 cm2; and group 3 was 2 channels per 1 cm2. Left ventricular
      myocardial viability and function were assessed by magnetic resonance imaging
      (MRI) and echocardiography pretreatment, and repeated 6 weeks later. RESULTS: The
      MRI assessment of group 1 (1 channel/2 cm2) and group 2 (1 channel/cm2)
      demonstrated similar improvement in segmental contractility posttreatment of
      12.11% +/- 5.15% and 12.47% +/- 9.51%, respectively. In contrast, group 3 (2
      channels/cm2) showed significantly worse segmental contractility posttreatment: 
      18.52% +/- 7.16% (p = 0.01). Echocardiographic imaging revealed significant
      improvements in wall thickening in the ischemic zone for group 1 at 0.91 +/- 0.07
      cm pretreatment versus 1.30 +/- 0.09 cm posttreatment, (p = 0.01); and for group
      2 at 0.93 +/- 0.11 cm versus 1.42 +/- 0.18 cm, (p = 0.01). No significant
      improvement in wall thickening was seen in group 3 (0.84 +/- 0.06 cm versus 0.88
      +/- 0.09 cm, p = n.s.). CONCLUSIONS: These data corroborate the empiric finding
      of an effective therapeutic dose range for TMR, 1 channel per 1 to 2 cm2. These
      results also demonstrate a detrimental effect when channel density is increased
      above the clinical standard of 1 channel per cm2 to a density of 2 channels per 1
      cm2.

PMID- 15464494
TI  - Fenoldopam prophylaxis of postoperative acute renal failure in high-risk cardiac
      surgery patients.
AB  - BACKGROUND: Acute renal failure requiring replacement therapy occurs in 1% to 2%
      of patients who have undergone cardiac surgery with cardiopulmonary bypass and is
      associated with a very high mortality rate. The aim of this study was to
      determine if prophylactic treatment with fenoldopam mesylate of patients at high
      risk of postoperative acute renal failure reduced the incidence of this event.
      METHODS: This was a multicenter, prospective, cohort study in which 108 patients
      at high risk of postoperative acute renal failure and undergoing cardiac surgery
      with cardiopulmonary bypass were treated with fenoldopam mesylate (0.08 microg x
      kg(-1) x min(-1)) starting at the induction of anesthesia and throughout at least
      the next 24 hours. A homogeneous control group of 108 patients was created using
      a propensity-score analysis. RESULTS: Fenoldopam prophylaxis was significantly
      associated with a reduction in acute renal failure incidence (from 22% to 11%, p
      = 0.028), a less pronounced creatinine clearance decrease (p = 0.05), and a lower
      mortality rate (6.5% versus 15.7%, p = 0.03) by the univariate analysis, but
      these results were not confirmed by a multivariable analysis. Within the subgroup
      of patients who suffered a postoperative low output syndrome, fenoldopam
      prophylaxis was an independent protective factor for postoperative renal failure
      (odds ratio, 0.14; 95% confidence interval, 0.03 to 0.7; p = 0.017). CONCLUSIONS:
      Given the limitations of a nonrandomized prospective trial, our results support
      the hypothesis that fenoldopam may reduce the risk of acute renal failure in
      patients in whom endogenous and exogenous cathecolamines action may induce a
      renal vascular constrictive condition.

PMID- 15464496
TI  - Clinical effectiveness of leukocyte filtration during cardiopulmonary bypass in
      patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: We tested the hypothesis that leukocyte filtration during pulmonary
      reperfusion preserves pulmonary function and results in improved oxygenation
      after cardiopulmonary bypass (CPB) in patients with chronic obstructive pulmonary
      disease (COPD). METHODS: In a prospective, randomized study, the treatment group
      consisted of 20 patients with COPD from consecutive open-heart procedures. A
      primed leukocyte filter was connected to the arterial line downstream of the
      standard arterial filter but was excluded from circulation. Circulated blood was
      directed through the leukocyte filter approximately 10 minutes before aortic
      cross-clamp removal and at early reperfusion for up to 30 minutes. These patients
      were compared to 20 additional COPD patients (controls) on whom systemic
      leukocyte filtration was not used during open-heart surgery. RESULTS: There was
      no significant difference in gender, age, left ventricular ejection fraction,
      type of procedure, aortic cross-clamp time, perfusion time, preoperative FEV1 and
      preoperative respiratory index (Pao2/FiO2 ratio) between treatment and control
      groups. The respiratory index changed in the treatment group by +9.8% of baseline
      after completion of CPB, by -14.2% upon arrival in the intensive care unit (ICU),
      and by -19.6% 12 hours later, whereas in the control group, it changed by -14.5%
      (p < 0.05), -27.7%, and -24%, respectively. Leukocyte-depleted patients required
      shorter intubation time (20.4 +/- 16.1 hours), ICU stay (46.2 +/- 40.1 hours) and
      length of hospitalization (8.3 +/- 2.8 days) than controls (29.5 +/- 21.9 hours,
      p < 0.05; 75.5 +/- 34.9 hours, p < 0.005; and 10.4 +/- 3.5 days, p < 0.05,
      respectively). Surgical (30-day) mortality was zero in both groups. CONCLUSIONS:
      In COPD patients having CPB, systemic leukocyte depletion at early reperfusion
      was associated with better oxygenation, shorter intubation time, and shorter ICU
      and hospital stays. Leukocyte filtration during CPB most likely preserves
      pulmonary function by ameliorating pulmonary reperfusion injury.

PMID- 15464497
TI  - Heterotopic heart transplantation: an expanding role in the twenty-first century?
AB  - BACKGROUND: Heterotopic heart transplantation was first performed in humans in
      1974, the main advantage being the continuing function of the patient's native
      heart, in the event of life-threatening acute rejection. The effect of
      cyclosporine on acute rejection saw the heterotopic transplantation technique
      wane. Our unit revisited heterotopic transplantation in response to a growing
      number of waiting list patients with high pulmonary artery pressures. We also
      anticipated an increased cardiac allograft utilization, and improvement of our
      waiting list times. METHODS: We retrospectively analyzed 151 patients undergoing
      heart transplantation by our unit between August 1997 and September 2003. Twenty
      received allografts in the heterotopic position. This cohort was compared with
      the 131 contemporary orthotopic heart transplant recipients with respect to their
      outcomes. RESULTS: The indication for transplantation was ischemic cardiomyopathy
      in 14 (70%) of the heterotopic cohort and 47 (36%) of the orthotopic cohort (p =
      0.004), and dilated cardiomyopathy in 3 (15%) and 48 (37%) in the heterotopic and
      orthotopic groups, respectively (p = 0.06). Heterotopic recipients were
      significantly older than orthotopic recipients, and they had higher pulmonary
      artery pressures. The heterotopic donors were also older and the ischemic times
      were longer. A subgroup analysis was made among those patients who had high
      pulmonary artery pressures as these groups were better matched. Major morbidity
      in the heterotopic heart transplantation group consisted of reversible allograft
      dysfunction in 4 patients, renal dysfunction requiring hemofiltration in 3
      patients, profound myopathy in 4 patients, and cerebrovascular events in 2
      patients. There were two early deaths in the heterotopic transplant group and
      eight in the orthotopic group (p = 0.87). Kaplan-Meier survival analysis of
      survival was performed. CONCLUSIONS: Heterotopic heart transplantation is a
      viable transplant option for selected high-risk heart transplant recipients in
      spite of somewhat poorer outcomes.

PMID- 15464499
TI  - Trends and outcomes in transplantation for complex congenital heart disease: 1984
      to 2004.
AB  - BACKGROUND: Cardiac transplantation for patients with complex congenital heart
      disease poses several anatomic and physiologic challenges for the transplant
      surgeon. We undertook the current single center study to evaluate surgical
      outcomes and lessons learned through a nearly twenty year experience with cardiac
      transplantation for complex congenital heart disease. METHODS: A retrospective
      review was performed to evaluate all patients undergoing cardiac transplantation
      from January 1, 1984 through January 1, 2004. Donor and recipient demographic and
      intraoperative and postoperative variables were acquired and correlated with
      perioperative (30-day) and late mortality in both univariate and multivariate
      analyses, and with Kaplan-Meier survival estimates. RESULTS: One hundred and six
      patients underwent transplantation for complex congenital heart disease and were
      followed for a median of 56 months. Thirty-seven (34.9%) patients died. Male
      gender and later year of transplantation were protective, and neonatal age and
      pulmonary artery reconstruction detrimental in multivariable modeling of overall
      mortality. Transplantation to a physiologic or anatomic single lung did not
      impact on survival. Patients in the study cohort had comparable survival
      estimates when compared with all those in the entire cohort without complex
      congenital heart disease. When comparing patients by era of transplantation, both
      cohorts demonstrated improved survival with later transplantation. CONCLUSIONS:
      Outcomes with transplantation for complex congenital heart disease have improved
      annually over the past twenty years. Transplantation to an anatomic or
      physiologic single lung did not impair overall survival. Pulmonary artery
      reconstruction imparted an increase in mortality both short and long term, a
      finding which merits further investigation.

PMID- 15464500
TI  - Optimizing donor heart outcome after prolonged storage with endothelial function
      analysis and continuous perfusion.
AB  - BACKGROUND: By minimizing tissue ischemia, continuous perfusion (CP) during organ
      transport may increase the safety of "marginal donors." My colleagues and I
      investigated whether an analysis of donor heart viability predicts recovery of
      grafts challenged with a 24-hour preservation interval. METHODS: Dog hearts
      underwent cold static storage (CS) for 8 hours (n = 8) or 24 hours (n = 2) or CP
      for 24 hours with cold asanguinous, oxygenated solution (n = 8). Myocardial
      systolic and diastolic function and oxygen and lactate consumption were assessed
      at base line, during CP, and after Langendorff blood reperfusion. Base line
      endothelial function was evaluated by the percentage transcoronary change
      ([coronary sinus - aorta]/aorta) in myeloperoxidase and by platelet function and
      coronary flow reserve after 20 seconds of coronary artery occlusion. During CP,
      the endothelium was assessed by transcoronary protein release and coronary
      resistance. Edema was assessed by weight gain and histology. RESULTS: Base line
      systolic and metabolic functions showed no relation to post-Langendorff function.
      Compared with CS, CP resulted in a greater recovery in systolic function (87% +/-
      35% vs 65% +/- 15% of baseline; p = 0.05) and a shorter interval required for
      lactate consumption to exceed production (7.0 +/- 6.8 minutes vs 15.0 +/- 8.9
      minutes; p = 0.06). Endothelial function was heterogeneous: coronary flow
      reserve, 2.7 +/- 0.7; percentage change in myeloperoxidase, -8.4% +/- 6.8%; and
      change in platelet function, 4.3% +/- 3.5%, as determined by thromboelastography
      angle at base line. Protein release during CP for 24 hours was 8.3 +/- 7.1 g. Two
      factors predicted more than 75% systolic pressure generation recovery: use of CP
      and normal endothelial function (p = 0.05; Fisher's exact test). However, CP led
      to edema according to histology, weight gain (72 +/- 29 g), and impaired
      diastolic function versus CS (end-diastolic pressure-volume relationship, 1.4 +/-
      0.4 mm Hg/mL vs 0.8 +/- 0.3 mm Hg/mL; p = 0.08). CONCLUSIONS: Better systolic
      function despite 16 hours' more preservation than cold storage corroborates the
      idea that CP supports aerobic metabolism at physiologically important levels.
      Viability analysis focused on endothelial function and identified organs that
      were able to tolerate this 24-hour preservation interval.

PMID- 15464501
TI  - Reevaluation of histomorphometric analysis of lung tissue in decision making for
      better patient selection for fontan-type operations.
AB  - BACKGROUND: The various types of cavopulmonary connection are occasionally
      unsuccessful even when the indications have been strictly fulfilled based on
      preoperative hemodynamic studies. We performed a detailed study of lung specimens
      from 60 patients who were judged to be candidates for the modified Fontan
      procedures based on a catheterizaton study in order to reevaluate the role of
      histologic studies of the pulmonary vasculature and to determine histologic
      criteria for the Fontan-type operation. METHODS: We performed a histomorphometric
      analysis of specimens from 53 biopsy and 7 autopsy cases (0.5 to 23 years of
      age), with single ventricle physiology. Twenty-eight cases were treated with a
      bidirectional Glenn shunt (BDGS) and 32 cases were treated by means of total
      cavopulmonary connections (TCPC) with or without fenestration, on the basis of
      the clinical and hemodynamic findings. To evaluate the medial thickness of small
      pulmonary arteries (SPAs), we used a measurement, D(R = 100 microm), that is
      unaffected by various degrees of vasoconstriction of the media or the age of the
      patients and that is representative of all SPAs in a section. Other variables,
      such as intimal lesions, SPA density, and the percentage of vessels containing a
      thrombus, were also measured. RESULTS: There was a significant difference in D(R
      = 100 microm) values between the BDGS cases with good and bad outcomes at p =
      0.0007 (8.9 +/- 2.4 versus 13.4 +/- 1.9 microm), and the cutoff point for the
      success of BDGS was 13.7 microm. The same was true of the TCPC cases at p less
      than 0.0001 (8.4 +/- 1.7 versus 14.7 +/- 1.5 microm), and the cutoff point was
      11.6 microm. There were no significant differences in other histomorphometric
      variables. Investigation of the relationship to hemodynamic data revealed a
      correlation between D(R = 100 microm) and mean pulmonary artery pressure at p =
      0.028. There were no statistically significant correlations between other
      variables. CONCLUSIONS: The study revealed marked differences in D(R = 100
      microm) values between patients with good and bad outcomes and provided D(R = 100
      microm) cutoff points for BDGS and TCPC. In some cases, there were discrepancies
      between the results of the preoperative hemodynamic data and of the
      histomorphometric analysis; and because some patients were wrongly assessed based
      on clinical and hemodynamic criteria, histomorphometric study might be a useful
      method of supplementing the variety of clinical data used to determine the
      indications for this operation.

PMID- 15464502
TI  - Bovine valved xenograft in pulmonary position: medium-term follow-up with
      excellent hemodynamics and freedom from calcification.
AB  - BACKGROUND: This study was designed to evaluate the outcome of Contegra xenograft
      valved conduit (Contegra, Medtronic Inc, Minneapolis, MN). METHODS: From April
      1999 to December 2003, 67 patients with a mean age of 16.1 +/-15.0 years (2
      months to 53 years) and a mean weight of 39.7 +/- 27.1 kg (4 to 95 kg) were
      discharged after implantation of a Contegra conduit. The diagnosis contained the
      following: pulmonary valve replacement during Ross operation (n = 27), pulmonary
      valve regurgitation (n = 9), tetralogy of Fallot (n = 7), pulmonary atresia with
      ventricular septal defect (n = 7), double outlet right ventricle (n = 7), truncus
      arteriosus (n = 5), Taussig-Bing (n = 2), obstructed conduit (n = 2), and double
      discordance (n = 1). Conduit size was 14 mm in 2, 16 mm in 7, 18 mm in 12, 20 mm
      in 13, and 22 mm in 33 patients. Mean cardiopulmonary bypass was 155 +/- 48 min
      (65 to 337 min) and mean aortic cross clamping was 69 +/- 38 min (0 to 146 min).
      All patients underwent echocardiography, 23 of 67 (34%) patients had cardiac
      catheterization, and 23 of 67 (34%) patients had electrocardiograph-gated
      multislice computer tomography. RESULTS: In a mean follow-up of 26.4 months (1 to
      56 months) there was one late death (1 of 67 patients; 1.5% mortality) unrelated
      to the conduit. Five patients underwent reoperation; four were nonconduit-related
      and one was to replace a twisted conduit. Five patients underwent interventional
      cardiology; three were nonconduit-related and two were to stent a twisted or
      stenotic conduit. Echocardiography showed absent valve regurgitation in 30 of 67
      (45%) patients, trivial in 21 of 67 (31%) patients, mild in 16 of 67 (24%)
      patients. The transconduit pressure gradient remained stable during follow-up,
      with peak pressure gradient 17 +/- 11 mm Hg and mean gradient 8 +/- 6 mm Hg.
      Internal diameters corresponded to 110% +/- 20% of the implanted diameter at
      level of proximal anastomosis, 112% +/- 18% at valve level, and 110% +/- 14% at
      distal anastomosis. Calcifications were not found, with the exception of a
      minimal (2.3 mm) parietal calcification. CONCLUSIONS: The Contegra valved conduit
      provided excellent morphology and hemodynamics, and freedom from calcification in
      a medium-term follow-up.

PMID- 15464503
TI  - An analysis of oxygen consumption and oxygen delivery in euthermic infants after
      cardiopulmonary bypass with modified ultrafiltration.
AB  - BACKGROUND: The balance between systemic oxygen consumption (VO2) and delivery
      (DO2) is impaired after cardiopulmonary bypass (CPB) and is related to systemic
      inflammatory response syndrome. We sought to assess VO2 and DO2 and their
      relationship with proinflammatory cytokines after CPB with the use of modified
      ultrafiltration (MUF) in infants. METHODS: Sixteen infants, aged 1-11.5 months
      (median, 6.3 months), undergoing hypothermic CPB with MUF were studied during the
      first 12 hours after arrival in the intensive care unit (ICU). The central
      temperature was maintained at 36.8-37.1 degrees C using external cooling or
      warming. VO2 was continuously measured using respiratory mass spectrometry.
      Arterial blood samples for the tumor necrosis factor (TNF), interleukin-6 (IL-6),
      and interleukin-8 (IL-8) were taken and DO2 was calculated using the Fick
      principle on arrival at the ICU, and 2, 4, 8, and 12 hours postoperatively.
      Cytokines were additionally measured after induction of anesthesia and at the end
      of MUF. RESULTS: VO2 significantly decreased by 18.8% during the study period.
      DO2 was depressed throughout this period and reached a nadir at 8 hours (357.1 +/
      136.2 ml x min(-1) x m(-2)). The decrease in cytokines was accompanied with the
      decrease in VO2 despite varied relationships between the levels of each of the
      cytokines and VO2 measurements. CONCLUSIONS: Our data indicate an unusual
      continuous decrease in VO2 during the first 12 hours after CPB in infants.
      Control of body temperature to maintain euthermia in addition to the use of MUF
      may be beneficial to the balance between VO2 and DO2 in the early postoperative
      period.

PMID- 15464504
TI  - Evaluation of epicardial microwave ablation lesions: histology versus
      electrophysiology.
AB  - BACKGROUND: Pulmonary vein isolation is a hallmark in current surgical ablation
      for atrial fibrillation. However, validation of isolation remains cumbersome. We
      evaluated electrophysiologic and not histologic means to test isolation. METHODS:
      In 16 mongrel dogs, robot-assisted epicardial beating-heart microwave ablation
      (FLEX 10) was performed around the pulmonary veins. Electrophysiologic isolation
      was tested by pacing at 4 times threshold values inside and outside the pulmonary
      veins (exit and entrance block). The histology of lesions was studied for
      transmurality and continuity of the lesion lines. In 5 dogs, lesions were studied
      at various time intervals. RESULTS: Histologic evaluation of the lesions showed
      incomplete (48% +/- 20%) circumferential myocardial damage in all dogs with acute
      lesions. Electrophysiologic evaluation showed completion of the box (entrance and
      exit block) in 8 dogs and in another 5 dogs after repeated ablation (p < 0.01
      compared with histologic evaluation). Electrophysiologic evaluation of the dogs
      with chronic lesions showed completed lesions in 4 of 5 dogs directly after
      ablation. At follow-up (1 to 3 weeks), the isolations remained
      electrophysiologically complete. Histologic evaluation of the lesions 1 to 3
      weeks after ablation showed complete (100%) circumferential lesions in all 4 dogs
      (p < 0.001 compared with the histology of dogs with acute lesions). CONCLUSIONS:
      Directly after treatment, ablation lesions are best evaluated
      electrophysiologically, because complete (transmural and circumferential) lesions
      are not shown by histologic evaluation in the acute stage. After 1 to 3 weeks,
      the histology is in accordance with the electrophysiology. To obtain a complete
      isolation, online electrophysiologic evaluation during pulmonary vein microwave
      ablation is necessary to optimize the results.

PMID- 15464505
TI  - Current status of surgery for rheumatic carditis in children.
AB  - BACKGROUND: The incidence of rheumatic heart disease (RHD) has increased recently
      in the western United States. We reviewed our 18-year surgical experience with
      RHD in children to examine current surgical techniques and results. METHODS: From
      1985 until 2003, 596 children (<21 years) with rheumatic fever were seen at
      Primary Children's Medical Center. Rheumatic carditis was diagnosed in 366
      patients (61.4%). Twenty-six with carditis (26/366, 7.1%) required operation for
      rheumatic valve disease including 8 for mitral regurgitation, 7 for mitral and
      aortic regurgitation, 4 for aortic regurgitation, 4 for mitral regurgitation and
      stenosis, 2 for combined mitral stenosis and regurgitation with aortic
      insufficiency, and 1 for mitral and tricuspid regurgitation. RESULTS: Mean age at
      operation was 13.5 +/- 4 years. Three patients required operation during the
      acute phase of rheumatic fever (< 6 weeks), 2 during the subacute phase (< 6
      months), and 21 during the chronic phase after the episode of rheumatic fever
      (6.7 +/- 3 years). Mitral valve repair was possible in 19 of 22 patients who
      required mitral operation. Aortic valve repair was possible in 4 patients whereas
      replacement was necessary in 9, including 2 Ross procedures. No operative deaths
      were recorded and 2 late deaths occurred at 4.6 and 10 years. Actuarial survival
      was 94% at 5 years and 78% at 10 years. Six patients required reoperation;
      actuarial freedom from reoperation was 78% at 5 years, 65% at 10 years, and 49%
      at 15 years. All survivors are in New York Heart Association class I or II.
      CONCLUSIONS: Children with RHD in the United States uncommonly require valve
      operation. Mitral repair with a technique that allows annular growth is possible
      in most children with good long-term functional results. Long-term surveillance
      of children with RHD is necessary because of the possible need for late valve
      operation.

PMID- 15464506
TI  - Repair of myocardial infarction by epicardial deposition of bone-marrow-cell
      coated muscle patch in a murine model.
AB  - BACKGROUND: Myocardial infarction results in irreversible myocyte loss. In a
      murine model, we tested the feasibility of a novel repair technique combining
      bone marrow cell (BMC) transplantation and cardiomyoplasty. METHODS: Myocardial
      infarction was induced cryogenically in backcrossed ROSA 26 transgenic x C57BL/6J
      mice (n = 75). Thirty days later, surviving mice (n = 69) were randomized to sham
      treatment (rethoracotomy only; n = 11), patch only treatment (n = 29), or patch +
      BMC treatment (n = 29). Abdominal muscle patches were harvested from donor
      littermates not expressing the beta-galactosidase reporter gene and sutured on
      the epicardium directly above the infarct zone. Patch only-treated mice received
      uncoated patches. Patch + BMC-treated mice received patches coated with 5 x 10(6)
      beta-galactosidase-expressing BMCs embedded in a collagen-rich three-dimensional
      matrix. RESULTS: Mortality rate was 52% after muscle patch implantation. Bone
      marrow cells were able to migrate from muscle patch into the infarct zone, as
      demonstrated by beta-galactosidase immunostaining, and ultimately constituted 8%
      of all cells in scar tissue (mean +/- standard deviation, 219 +/- 111/mm2).
      Angiogenesis and cell survival in the scar were improved by patch + BMC
      treatment. Left ventricular geometry and cardiac function were improved by patch
      treatment, with or without BMC, although the effects were stronger after patch +
      BMC treatment. CONCLUSIONS: Epicardial deposition of a BMC-coated muscle patch is
      a promising approach to restoring cardiac function after myocardial infarction.

PMID- 15464507
TI  - Increased transcription factor expression and permeability of the blood brain
      barrier associated with cardiopulmonary bypass in lambs.
AB  - BACKGROUND: The pathophysiology of neurocognitive dysfunction and developmental
      delay after cardiopulmonary bypass (CPB) in infants is not known. It is known
      that head trauma, stroke, and seizures cause dysfunction of the blood brain
      barrier (BBB) that is associated with increased inducible transcription factor
      gene expression in the cells of the barrier. The purpose of this study was to
      determine the effects of CPB and hypothermic circulatory arrest on expression of
      the transcription factor FOS and the function of the BBB in an infant animal
      model. METHODS: Infant lambs (n = 36; 10-12 days) were exposed to 0, 15, 30, 60,
      or 120 minutes of normothermic (38 degrees C) CPB or 2 hours of hypothermic
      circulatory arrest at 16 degrees C. After terminating bypass 15 animals had their
      brains perfusion-fixed and removed for immunohistochemical analysis of expression
      of the transcription factor FOS. The other animals were perfused with fluorescent
      albumin to visualize the brain microvasculature. Brain sections were analyzed
      with a laser scanning confocal microscope. RESULTS: Control animals (n = 6, sham
      operated and cannulated) exhibited normal vasculature with negligible leakage and
      no FOS protein expression in neurons or endothelial cells anywhere in the brain.
      Significant FOS expression in barrier-associated structures including the blood
      vessels, choroid plexus, and ependyma but not neurons occurred at all times on
      bypass. CPB caused leakage of fluorescent albumin from blood vessels in all
      animals. Two hours of normothermic CPB (n = 4) caused significant (p < 0.01)
      leakage in the cerebellum, cortex, hippocampus, and corpus callosum. Animals
      exposed to circulatory arrest experienced severe leakage throughout the brain (p
      < 0.001) and FOS expression in all cells. CONCLUSIONS: These experiments indicate
      that the BBB is dysfunctional after all time points on normothermic CPB, BBB
      dysfunction is worsened by hypothermic circulatory arrest, and BBB dysfunction is
      associated with intense molecular activity within the barrier-forming cells.
      Dysfunction of the BBB may contribute to neurologic complications after heart
      surgery.

PMID- 15464508
TI  - Intraaortic balloon pumping improves hemodynamics and right ventricular
      efficiency in acute ischemic right ventricular failure.
AB  - BACKGROUND: Left ventricular unloading has a potentially deleterious effect in
      right ventricular failure as a result of altered septal interplay. However, a
      positive effect of an intraaortic balloon pump during right ventricular failure
      has been suggested. We investigated the impact of intraaortic balloon pumping on
      hemodynamics and both left and right ventricular function in an experimental
      model of isolated right ventricular failure. METHODS: Sixteen anesthetized pigs
      (25 to 34 kg) were used in an in vivo model. Pressure-conductance catheters
      assessed right and left ventricular pressure-volume relationships. Acute right
      ventricular failure was induced by right coronary microembolization, and led to
      severely impaired right ventricular function, reduced cardiac output and arterial
      pressure, and an increased pulmonary vascular resistance and pulmonary arterial
      elastance. Animals were then randomized to balloon pump or control groups and
      evaluated with respect to hemodynamics and ventricular function after 1 hour.
      RESULTS: Intraaortic balloon pumping did not alter right or left ventricular
      contractility. However, balloon pump-treated animals had significantly improved
      cardiac output (+18% +/- 18% versus -6% +/- 7%; p = 0.003) and mean arterial
      pressure (+36% +/- 30% versus -7% +/- 14%; p = 0.004) compared with controls.
      Animals in the balloon pump group had lower pulmonary vascular resistance (795 +/
      63 versus 912 +/- 259 dynes . sec . cm(-5); p < 0.01) and pulmonary arterial
      elastance (1.14 +/- 0.20 versus 1.69 +/- 0.65 mm Hg/mL; p < 0.01), and increased
      stroke volume (22.3 +/- 4.7 versus 17.9 +/- 4.7 mL; p = 0.016). Right ventricular
      efficiency was also improved in the balloon pump group (stroke work per pressure
      volume area = 0.60 +/- 0.14 versus 0.41 +/- 0.12; p < 0.01). CONCLUSIONS:
      Intraaortic balloon pump support does not alter right or left ventricular
      function in acute right ventricular failure. However, arterial pressure, cardiac
      output, and right ventricular efficiency are improved, possibly because of a
      balloon pump-induced reduction in pulmonary arterial resistance.

PMID- 15464510
TI  - New tubular bioabsorbable knitted airway stent: feasibility assessment for
      delivery and deployment in a dog model.
AB  - PURPOSE: The aim of this study was to determine whether it is possible to deliver
      and deploy a new device, a poly-L-lactic acid (PLLA) tubular knitted airway
      stent, under bronchoscopic guidance in a dog model. DESCRIPTION: The delivery
      system consisted of a flexible balloon catheter (controlled radial expansion
      balloon dilator, M00558440, Boston Scientific Corporation, MA, USA) preloaded
      with a stent. A delivery catheter preloaded with a stent was advanced to a target
      point in the trachea under bronchoscopic guidance. Once the stent was positioned,
      the balloon was inflated for sixty seconds. The stent was in full contact with
      the tracheal wall upon deflation of the balloon. EVALUATION: The stents were
      successfully delivered into the tracheal lumen and successfully deployed in all
      dogs. CONCLUSIONS: This is the first study to prove the feasibility of delivering
      and deploying the PLLA stents in a dog model, using a balloon expansion
      technique. Further investigation with large numbers of subjects and long-term
      follow-up will be necessary to assess the utility of the bioabsorbable knitted
      tubular stent before clinical applications begin.

PMID- 15464509
TI  - Effects of a new phosphodiesterase enzyme type V inhibitor (UK 343-664) versus
      milrinone in a porcine model of acute pulmonary hypertension.
AB  - BACKGROUND: Perioperative pulmonary hypertension remains a clinical challenge.
      The phosphodiesterase enzyme type III inhibitor milrinone produces pulmonary
      vasodilation but lacks selectivity. Sildenafil, a phosphodiesterase enzyme type V
      inhibitor, can also induce relaxation of the pulmonary vasculature; however, only
      the oral formulation is presently available. This study evaluated the effects of
      a new intravenous sildenafil analogue--UK 343-664--compared with milrinone during
      acute pulmonary hypertension in a porcine model of thromboxane-induced pulmonary
      hypertension. METHODS: After acute pulmonary hypertension, 24 adult swine were
      randomized to 3 groups. Group 1 (n = 9) received an intravenous dose of 500
      microg of UK 343-664, group 2 (n = 8) received milrinone 50 mg/kg, and group 3 (n
      = 7) received 10 mL of normal saline solution. All agents were administered for
      more than 5 minutes. Data were recorded continuously for 30 minutes. RESULTS:
      Both milrinone and UK 343-664 partially reversed thromboxane-induced pulmonary
      hypertension, with a notable decrease in mean pulmonary artery pressure and
      pulmonary vascular resistance and a concomitant increase in cardiac output. In
      addition, milrinone improved right ventricular contractility but produced marked
      systemic vasodilatation. In contrast, the administration of UK 343-664 was
      associated with pulmonary vasodilatation, without appreciable changes in systemic
      arterial pressure or vascular resistance. CONCLUSIONS: Milrinone and UK 343-664
      were equally effective as pulmonary vasodilators; however, only UK 343-664
      exhibited a high degree of pulmonary selectivity. Potential uses for this new
      phosphodiesterase enzyme type V inhibitor warrant further study.

PMID- 15464511
TI  - Multivessel, all-arterial, off-pump surgical revascularization without disruption
      of the thoracic skeleton.
AB  - PURPOSE: To evaluate the feasibility of performing multivessel off-pump surgical
      revascularization without manipulation of the thoracic cage. DESCRIPTION: The
      technique consists of bilateral thoracoscopic internal mammary artery harvesting
      followed by a nonrib-spreading, muscle-sparing opening in the soft tissue of the
      thorax. An endoscopic cardiac positioner and stabilizers exposes and steadies the
      target arteries beneath a small opening. Anastomoses are constructed off-pump
      through the natural width of the intercostal space without the need for rib
      spreading. EVALUATION: Fifty-two patients underwent all-arterial, off-pump
      revascularization through incisions avoiding manipulation of the thoracic
      skeleton. The mean number of grafts per patient was 2.2 +/- 0.4. Transit time
      flow measurements verified graft patency before closure in all cases. The mean
      operating time was 4.4 hours (range, 3.4 to 5.6). Hospital length of stay was 2.6
      +/- 1.9 days. There was no early or late mortality. Postoperative angiography
      performed in 63.8% of the grafts (74 of 116) revealed an overall patency rate of
      98.6%. CONCLUSIONS: A grafting approach that avoids any manipulation of the
      thoracic skeleton offers significant patient value and may not be limited to
      single-graft cases.

PMID- 15464513
TI  - Extratracheal biodegradable splint to treat life-threatening tracheomalacia.
AB  - A 9-month-old girl presented with life-threatening acute respiratory failure 1
      week after the surgical correction of a double aortic arch, which was due to a
      severe bulging of the pars membranacea into the lumen of the trachea that
      produced a complete obstruction of the lower trachea. Under cardiopulmonary
      bypass, a Y-shaped posterior biodegradable splint was placed behind the trachea
      and sutured to the posterior trachea, and a simultaneous right aortic arch
      aortopexy was performed. Thereafter, the child recovered normal respiratory
      function. Follow-up bronchoscopy showed a posterior dip at the splint level and
      an asymptomatic persistent posterior compression of the right main bronchus.

PMID- 15464514
TI  - Primary solitary endobronchial plasmacytoma.
AB  - Twenty-two cases of pulmonary plasmacytoma have been reported in the literature
      and verified by immunohistochemistry or other diagnostic tests. The treatment for
      this rare tumor has included various combinations of surgical resection,
      chemotherapy, and radiation therapy. We report a case of a middle-age man who
      underwent endoscopic debulking followed by laser ablation for a pulmonary
      plasmacytoma, which showed a prominent endobronchial location with clinical and
      histopathologic verification.

PMID- 15464515
TI  - Management of bronchovascular mucormycosis in a diabetic: a surgical success.
AB  - Although cases of pulmonary mucor are scarce, diabetics account for a large
      percentage of these patients. The synergism of diabetes mellitus and mucormycosis
      poses potentially devastating bronchopulmonary complications, warranting urgent
      intervention. This report reviews the efficient workup, along with successful
      medical and surgical management, of a patient with pulmonary mucormycosis, with
      evidence of superior vena cava invasion.

PMID- 15464516
TI  - Bland-White-Garland syndrome in a 39-year-old mother.
AB  - We report the case of a 39-year-old mother of 3 children presenting with exertion
      fatigue. Coronary angiography revealed an anomalous left coronary artery arising
      from the pulmonary artery. The patient underwent an operation with the direct
      implantation of the left coronary artery into the ascending aorta. This less
      symptomatic course stands in contrast to the high risk for sudden death in
      untreated adults.

PMID- 15464517
TI  - Aspergillus endocarditis in a native valve after amphotericin B treatment.
AB  - Systemic infection with Aspergillus fumigatus is an opportunistic disease that
      affects mainly immunocompromised hosts and is associated with a high mortality
      rate. We report a case of A. fumigatus endocarditis after an episode of
      thrombotic thrombocytopenic purpura. Diagnosis was established after sudden
      rupture of posterior papillary muscle of the normal native mitral valve. Soon
      after mitral valve replacement, Aspergillus endocarditis recurred, associated
      with multiple peripheral emboli, which necessitated a second operation.

PMID- 15464518
TI  - Mycotic aortocoronary saphenous vein graft aneurysm presenting with unstable
      angina pectoris.
AB  - We report the case of a 60-year-old man with a history of coronary bypass surgery
      20 years prior who had a fever, chest pain, and a mediastinal mass develop after
      a complicated postoperative course of abdominal aortic aneurysm resection. A
      mycotic aneurysm of the saphenous vein graft to his left anterior descending
      coronary artery was diagnosed based on blood culture results and visualization of
      the aneurysm before resection. A summary of the saphenous vein graft aneurysm and
      pseudoaneurysm cause, diagnosis, and management is detailed.

PMID- 15464519
TI  - Selective arterialization of the coronary venous system.
AB  - The idea of myocardial revascularization by means of grafting the coronary venous
      system is more than a century old; in cases of diffuse coronary artery disease,
      this may represent a valid therapeutic option. We present a challenging case in
      which a patient with an aberrant left coronary system and unstable angina
      underwent this type of procedure with good clinical results.

PMID- 15464520
TI  - OPCAB surgery in a cirrhotic hepatocellular carcinoma patient awaiting liver
      transplant.
AB  - Cirrhosis was once thought of as an absolute contraindication to cardiac surgery
      with the risk of liver decompensation following the use of cardiopulmonary
      bypass. With the advent of off-pump coronary artery bypass grafting, the
      possibility of reducing the risk of decompensation may make this type of surgery
      suitable for patients who will eventually undergo orthotopic liver
      transplantation. We present the strategy used in a patient with multifocal
      hepatocellular carcinoma and cirrhosis who underwent coronary artery bypass
      grafts for unstable angina, in order to allow him to undergo liver
      transplantation at a future date.

PMID- 15464521
TI  - Combined surgical and endovascular approach to treat a complex aortic coarctation
      without extracorporeal circulation.
AB  - Various therapeutic approaches have been proposed to treat complex coarctation of
      the aorta (eg, recoarctation, which requires repetitive interventions, or
      coarctation with a hypoplastic aortic arch). Resection followed by end-to-end
      anastomosis or by graft interposition is technically demanding and exposes the
      patient to considerable perioperative risks. Cardiopulmonary bypass and deep
      hypothermic circulatory arrest may be necessary to control the distal aortic
      arch. The role of stent technology in treating this type of lesion has not yet
      been defined. We present a 21-year-old woman with a recurrent coarctation of the
      aorta associated with a hypoplastic aortic arch and a pseudoaneurysm of the
      proximal descending aorta. She had undergone 4 previous interventions. Treatment
      consisted of a combined surgical and endovascular approach without
      cardiopulmonary bypass and included extraanatomic aortic bypass, partial
      debranching of the supraaortic vessels, and stent-graft insertion to exclude the
      aneurysm.

PMID- 15464522
TI  - Atresia of the right vertebral artery in a patient with acute aortic dissection.
AB  - A 49-year-old man had severe neurocognitive dysfunction after urgent operation
      for acute type A aortic dissection. Complete aortic arch replacement with single
      reimplantation of the arch branches was performed with the patient under deep
      hypothermic circulatory arrest. Retrospectively, my colleagues and I consider the
      atresia of the right vertebral artery to be responsible for this complication and
      discuss whether knowledge of the anomaly and adapting the operative strategy
      accordingly would have improved the neurologic outcome.

PMID- 15464523
TI  - Replacement of a regurgitant pulmonary valve with a stentless bioprosthesis.
AB  - Acquired surgical disease of the pulmonary valve is rare. We report a 72-year-old
      man who presented with subacute endocarditic pulmonary regurgitation. This lesion
      was surgically corrected with a stentless bioprosthesis. Previously, homografts
      and various xenografts have been used for replacement of the pulmonary valve both
      in the pediatric population and in adult patients with congenital heart disease.
      Pulmonary regurgitation is a rare lesion, but if it is encountered our case
      demonstrates that it can be successfully and easily treated with pulmonary valve
      replacement by using a stentless bioprosthesis.

PMID- 15464524
TI  - Cardiac angiosarcoma arising from pulmonary artery: endovascular treatment.
AB  - We report a case of unusual origin of cardiac angiosarcoma rising from the
      pulmonary trunk. The tumor caused severe obstruction of the right ventricular
      outflow tract with serious symptoms of right ventricular failure and tricuspid
      insufficiency. The angiosarcoma was surgically unresectable because of
      infiltration of the pulmonary artery and cardiac structures. To relieve the
      patient's symptoms we chose an endovascular stent treatment to dilate the right
      ventricular outflow tract obstruction. Consequently this palliative treatment
      changed the short-term prognosis of the patient, improving his quality of life,
      and at 6 months follow-up he remains asymptomatic.

PMID- 15464525
TI  - Combined radiofrequency ablation and myxoma resection through a port access
      approach.
AB  - Myxomas are common cardiac tumors that are traditionally managed by complete
      excision through a median sternotomy approach with the use of cardiopulmonary
      bypass. We discuss a patient with left atrial myxoma and chronic atrial
      fibrillation who underwent surgical excision and combined irrigated
      radiofrequency ablation for atrial fibrillation through a Port Access approach.
      Minimally invasive operations constitute an expanding field for the treatment of
      many cardiac diseases and may be an alternative for the treatment of this
      pathology because of less surgical trauma and cosmetic superiority. In this case,
      both excision of the myxoma and radiofrequency ablation were feasible through
      this minimally invasive approach. The combination of direct and endoscopic views
      enabled both procedures to be performed safely and efficiently.

PMID- 15464526
TI  - Recurrent pericardial tamponade from atrial hemangioma.
AB  - We encountered a 72-year-old woman with a left atrial hemangioma arising in the
      appendage and growing like an extracardiac mass. Life-threatening cardiac
      tamponade, recurrent over a 5-year clinical course, was the only sign of this
      rare tumor. The extraatrial growth pattern of the tumor made it difficult to
      distinguish the cardiac origin from a paracardiac mass. With the aid of
      cardiopulmonary bypass, the tumor was removed from the left atrium at the base of
      the appendage. Pathologic diagnosis was a combination of cavernous- and venous
      type hemangioma. The postoperative course was uneventful, and the patient was
      doing well with no pericardial effusion at the 10-month follow-up.

PMID- 15464527
TI  - HLHS with severe aortic insufficiency in a patient with 45,X/46,XY mosaicism.
AB  - Aortic insufficiency is not a part of the hypoplastic left heart syndrome. This
      report describes a rare case of congenital aortic insufficiency from a detached
      leaflet in a patient with hypoplastic left heart syndrome and 45,X/46XY
      mosaicism. The patient was subsequently treated with the modified Norwood
      procedure along with suture closure of aortic valve.

PMID- 15464528
TI  - False aneurysm in pulmonary sequestration.

PMID- 15464529
TI  - Pseudoaneurysm after Bentall operation diagnosed by transesophageal
      echocardiography.

PMID- 15464531
TI  - The use of aortic connector as shunt during endarterectomy of innominate artery.
AB  - The St. Jude aortic connector system (St. Jude Medical, Inc, St. Paul, MN) is
      being increasingly used for the construction of vein proximal anastomosis in
      coronary artery bypass grafting. We suggest a possible use of the connected vein
      as temporary shunt during open endarterectomy of the innominate artery and at the
      same time as graft for coronary artery bypass grafting.

PMID- 15464530
TI  - Simple modification of "T. David-V" valve-sparing aortic root replacement to
      create graft pseudosinuses.
AB  - The absence of sinuses of Valsalva is postulated to perturb coronary flow
      patterns and to create abnormal leaflet stresses, which theoretically may limit
      the long-term durability of valve-sparing aortic root replacement with the
      original Tirone David-I reimplantation technique with a cylindrical tube graft.
      David developed the "T. David-V" procedure in 2001; it creates large billowing
      Dacron pseudosinuses while retaining the reimplantation concept. To illustrate a
      simple modification of the T. David-V technique, we describe a patient with
      Marfan's syndrome who underwent valve-sparing aortic root replacement with 1
      large and 1 small graft to create pseudosinuses in the Dacron graft, to
      facilitate suturing the valve inside the graft, and to make the distal graft-to
      aorta anastomosis a better size match.

PMID- 15464532
TI  - A method to avoid annular downsizing during knot tying.
AB  - Pericardial annuloplasty has been used as an alternative to prosthetic
      annuloplasty. One drawback of pericardial annuloplasty is the risk of cinching of
      tissues during knot tying, possibly leading to uncontrolled downsizing and to
      complications such as mitral stenosis and systolic anterior motion of the
      anterior leaflet. A simple modification of the sequence of knot tying is
      described to avoid this complication.

PMID- 15464533
TI  - Tricuspid valve repair with papillary muscle shortening for severe tricuspid
      regurgitation in children.
AB  - We describe tricuspid valve repair using papillary muscle shortening for severe
      tricuspid regurgitation due to leaflet prolapse in children combined with De Vega
      annuloplasty. The papillary muscle was shortened until the prolapsed leaflet was
      at the same height as the other nonprolapsed leaflets. Although echocardiographic
      tricuspid regurgitation tends to increase over time, it rarely requires long-term
      intervention.

PMID- 15464534
TI  - The Ross II procedure: pulmonary autograft in the mitral position.
AB  - The surgical management of mitral valve disease in women of childbearing age,
      young patients, and children with congenital mitral valve defects is made
      difficult by the prospect of lifelong anticoagulation. We suggest the use of a
      pulmonary autograft in the mitral position (Ross II procedure) as an alternative
      surgical technique. We present a review of the literature, historical
      perspectives, indications, selection criteria, and surgical technique for the
      Ross II procedure. Our literature search identified 14 studies that reported
      results from the Ross II operation. Performed in 103 patients, the overall in
      hospital mortality was 7 (6.7%), with a late mortality of 10 (9%). Although
      further research is needed, current evidence suggests the Ross II operation is a
      valuable alternative in low-risk young patients where valve durability and the
      complication rate from other procedures is unsatisfactory and anticoagulation not
      ideal.

PMID- 15464535
TI  - Sildenafil: emerging cardiovascular indications.
AB  - The discovery in 1989 of sildenafil, a highly selective inhibitor of
      phosphodiesterase-5 (PDE-5), was the result of extensive research on chemical
      agents targeting PDE-5 that might potentially be useful in the treatment of
      coronary heart disease. Initial clinical studies on sildenafil in the early 1990s
      were not promising with respect to its antianginal potential. However, the
      incidental discovery of its antiimpotence effect led to its approval of for the
      treatment of erectile dysfunction. Thereafter, several reports of adverse cardiac
      events in patients on sildenafil raised concerns about its safety in
      cardiovascular disorders. Novel therapeutic indications are emerging for
      sildenafil with the recent discovery that PDE-5 is expressed in various other
      tissues such as the arterial vasculature, including pulmonary and coronary
      arteries, venous vasculature, skeletal muscles, platelets, and visceral and
      tracheobronchial muscles. In this review we briefly summarize the pharmacology of
      sildenafil and the current available evidence on its potential therapeutic
      applications in cardiovascular disorders.

PMID- 15464536
TI  - Adenosquamous carcinoma of the lung and visceral pleural invasion.

PMID- 15464538
TI  - Tracheal ring regeneration.

PMID- 15464539
TI  - Octreotide in bronchobiliary fistula management.

PMID- 15464541
TI  - Apparent reduction of cerebral microemboli during off-pump operations.

PMID- 15464544
TI  - The quality of the coronary arteries influences the outcome of bypass surgery.

PMID- 15464546
TI  - Cause of degenerative disease of the trileaflet aortic valve.

PMID- 15464549
TI  - Diagnosis of phrenic nerve injury after cardiac surgery.

PMID- 15464550
TI  - Lasers in clinical dentistry.

PMID- 15464551
TI  - Fundamentals of dental lasers: science and instruments.
AB  - This article provides the reader with an understanding of the essential physical
      science of a laser device. Various dental tissues have unique interactions with
      laser light, and the principles of safe and effective use of this unique
      instrument are presented. Each wavelength's applications for treatment are
      outlined.

PMID- 15464552
TI  - The biologic rationale for the use of lasers in dentistry.
AB  - Dentists have a variety of wavelengths to choose from when purchasing a laser.
      Each wavelength has a unique interaction with the target tissues of the oral
      cavity. This article gives a rationale, grounded in sound biologic principles,
      for the use of different wavelengths in the oral cavity. Advantages and
      disadvantages of the various wavelengths for specific procedures are discussed.

PMID- 15464553
TI  - Dental laser safety.
AB  - The purpose of this article is to inform the reader about dental laser safety and
      to suggest practical guidelines. The laser safety officer plays a major role,
      ensuring that the instrument is used safely and effectively. With adequate
      precautions and proper training, dental lasers can be used to deliver excellent
      care.

PMID- 15464554
TI  - Lasers in endodontics.
AB  - With the rapid development of laser technology, new lasers with a wide range of
      characteristics are now available and being used in various fields of dentistry.
      In the past two decades, much experience and knowledge has been gained. This
      article provides an overview of the current and possible future clinical
      applications of lasers in endodontics, including their use in alleviating
      dentinal hypersensitivity, modification of the dentin structure, pulp diagnosis,
      pulp capping and pulpotomy, cleaning and shaping of the root canal system, and
      endodontic surgery. Endodontic procedures for which conventional treatments
      cannot provide comparable results or are less effective are emphasized.

PMID- 15464555
TI  - Lasers in aesthetic dentistry.
AB  - This article focuses on lasers and aesthetic dentistry and their unique parallel
      in history from their early development to their present day usage and
      application. The demand for aesthetic dentistry has had a major impact not only
      on treatment planning but also on the choice of materials, techniques, and
      equipment. It is this demand that has married the use of lasers with aesthetic
      dentistry. A short literature review on the five basic laser types precedes the
      basic premise of smile design and its critical importance in attaining the
      desirable aesthetic end result. A short review on biologic width and biologic
      zone reinforces their importance when manipulating gingival tissue. Four case
      reports highlight the use of diode, erbium, and carbon dioxide lasers. The end
      results show the power of proper treatment planning and the use of a smile design
      guide when using these instruments and confirm a conservative, aesthetic
      treatment without compromising the health and function of the patients.

PMID- 15464556
TI  - Lasers in contemporary oral and maxillofacial surgery.
AB  - The practice of oral and maxillofacial surgery has included the use of lasers
      since the 1960s. Over the past few decades, the use of lasers among oral and
      maxillofacial surgeons has grown dramatically. Their evolution within the
      specialty not only has enhanced current surgical options for treatment, but also
      contributed to a variety of new procedures that are now commonplace in oral and
      maxillofacial surgery. The management of patients with sleep apnea,
      temporomandibular joint derangements, dental implants, premalignant lesions, and
      posttraumatic facial scarring has improved significantly with the advent of laser
      surgery. As the number of laser systems grows and their technology becomes more
      advanced, a thorough understanding regarding the principles of their use is
      paramount to providing safe and effective patient care.

PMID- 15464557
TI  - Lasers in pediatric dentistry.
AB  - Pediatric dentistry's mission in delivering care to our young patients is simple:
      provide optimal preventive, interceptive, and restorative dental care in a stress
      free environment. Lasers such as argon, diode, Nd:YAG, CO2, and now the erbium
      family enable minimally invasive dentistry for hard- and soft-tissue procedures.
      This article offers an understanding of treatment planning in the pediatric
      practice and demonstrates the procedures that dental lasers can perform on
      younger patients.

PMID- 15464558
TI  - Lasers for initial periodontal therapy.
AB  - With a greater understanding of the components that initiate the host into the
      downward spiral of periodontal disease, the clinician must look for better
      treatment and therapy options. Clinical observations and studies show good
      results, making incorporation of the laser into the first phase of nonsurgical
      periodontal therapy an excellent choice.

PMID- 15464559
TI  - Lasers in surgical periodontics and oral medicine.
AB  - Surgical lasers rapidly are becoming part of the periodontal armamentarium. This
      article discusses the different lasers that are suitable for use on the soft
      tissues of the periodontium. Various laser-assisted periodontal surgical
      procedures and laser treatment of diseases of the oral mucosa are discussed.

PMID- 15464560
TI  - Clinical applications of lasers during removable prosthetic reconstruction.
AB  - The successful construction of removable full and partial dentures depends mainly
      on the preoperative evaluation of the supporting hard and soft tissue structures
      and their proper preparation. Stability, retention, function, and esthetics of
      removable prostheses may be enhanced by proper laser manipulation of the soft
      tissues and underlying osseous structure. Compared with conventional techniques,
      laser treatment has many advantages. More predictable postoperative healing
      results and shortened treatment time may be achieved when lasers are integrated
      into the treatment plan for construction of removable prosthetic devices.

PMID- 15464561
TI  - The use of lasers in fixed prosthodontics.
AB  - The delivery of fixed prosthodontics demands of the clinician a responsible level
      of skill, accuracy, and predictability commensurate with previous experience and
      ability. The patient often demands speed and cosmetics. The appropriate
      employment of laser wavelengths, when indicated and supported by scientific
      evidence, can enhance the applicable factors favorable to the clinician and
      patient.

PMID- 15464562
TI  - Lasers in dental implantology.
AB  - The parallels in the expansion of implant dentistry and laser dentistry in
      clinical practice are apparent. As advocates for laser dentistry continue to seek
      new ways to use the technology and as more practitioners become involved in
      implant dentistry, it is logical to see the concurrent use of both technologies
      in clinical practice. This article provides data that clearly support the value
      of dental lasers in the practice of implant dentistry. The challenge for the
      practitioner is the same as for any other area of dentistry: knowing when, where,
      and what armamentarium to use in any given situation. Not all dental laser
      wavelengths are necessarily useful in every dental implant situation. After
      clinicians know the characteristics of the wavelengths available to them, the
      application of the technology to the specific situation certainly is warranted.

PMID- 15464563
TI  - Erbium lasers in dentistry.
AB  - Erbium hard tissue lasers have the capability to prepare enamel, dentin, caries,
      cementum, and bone in addition to cutting soft tissue. The ability of hard tissue
      lasers to reduce or eliminate vibrations, the audible whine of drills,
      microfractures, and some of the discomfort that many patients fear and commonly
      associate with high-speed handpieces is impressive. In addition, these lasers can
      be used with a reduced amount of local anesthetic for many procedures. Today,
      these instruments have evolved from their initial use for all classes of cavity
      preparations to their ability for removing soft tissue, their usefulness in the
      disinfection of bacteria within endodontic canals, and most recently, as an
      alternative to the high speed handpiece for the removal of bone in oral and
      maxillofacial surgery. In addition, recent research has centered on the value of
      the erbium family of laser wavelengths in periodontics, including the removal of
      calculus.

PMID- 15464564
TI  - Low-level laser therapy in dentistry.
AB  - Low-level laser therapy (LLLT) is a newly developing technique in dentistry,
      although it has been used among medical, dental, physiotherapy, and veterinary
      professions in some parts of the world for decades. LLLT can offer tremendous
      therapeutic benefits to patients, such as accelerated wound healing and pain
      relief. There is much to be learned about the mechanisms, recognition of the
      therapeutic window, and how to properly use these cellular phenomena to reach the
      treatment goals.

PMID- 15464565
TI  - Dental laser research: selective ablation of caries, calculus, and microbial
      plaque: from the idea to the first in vivo investigation.
AB  - One of the current dental laser research tracks is selective ablation, which is
      the removal of disease while not harming adjacent healthy structures. This
      article describes the scientific path from the first basic laboratory study of
      the absorption characteristics of caries to selective ablation of bacteria,
      microbial plaque, and calculus with a blue laser and the first in vivo safety
      studies in dogs. This article is an example of a typical research path for future
      studies of the uses of lasers in dentistry.

PMID- 15464566
TI  - Laser dentistry practice management.
AB  - Laser treatment in promoting dental care is present in many areas and
      disciplines. The public has an expectation that their dentist should be up to
      date with the most modern and advanced care possible. The future of lasers in
      dentistry is promising. New applications and procedures are constantly being
      developed. Dentists who position themselves to provide and manage these new
      technologies stand to be rewarded from clinical and financial aspects. Proper
      practice management strategies are key to achieving this success.

PMID- 15464567
TI  - Evaluating dental lasers: what the clinician should know.
AB  - According to the Institute for Advanced Dental Technologies, dental lasers have
      obtained approximately a 6% market penetration in the United States.
      Unfortunately, a small percentage of doctors have been disappointed with the
      technology. This article has been written as a guide for clinicians to use before
      purchasing a dental laser. It is the hope of the authors that this material will
      allow the clinicians to have a better appreciation of this technology and
      maximize its successful integration into practice.

PMID- 15464568
TI  - Induction of the neural crest and the opportunities of life on the edge.
AB  - The neural crest is a multipotent population of migratory cells unique to the
      vertebrate embryo. Neural crest arises at the lateral edge of the neural plate
      and migrates throughout the embryo to give rise to a wide variety of cell types
      including peripheral and enteric neurons and glia, craniofacial cartilage and
      bone, smooth muscle, and pigment cells. Here we review recent studies that have
      addressed the role of several signaling pathways in the induction of the neural
      crest. Work in the mouse, chick, Xenopus, and zebrafish have shown that a complex
      network of genes is activated at the neural plate border in response to neural
      crest-inducing signals. We also summarize some of these findings and discuss how
      the differential activation of these genes may contribute to the establishment of
      neural crest diversity.

PMID- 15464569
TI  - Receptor protein tyrosine phosphatases regulate neural development and axon
      guidance.
AB  - The regulation of tyrosine phosphorylation is recognized as an important
      developmental mechanism. Both addition and removal of phosphate moieties on
      tyrosine residues are tightly regulated during development. Originally, most
      attention focused on the role of tyrosine kinases during development, but more
      recently, the developmental importance of tyrosine phosphatases has been gaining
      interest. Receptor protein tyrosine phosphatases (RPTPs) are of particular
      interest to developmental biologists because the extracellular domains of RPTPs
      are similar to those of cell adhesion molecules (CAMs). This suggests that RPTPs
      may have functions in development similar to CAMs. This review focuses on the
      role of RPTPs in development of the nervous system in processes such as axon
      guidance, synapse formation, and neural tissue morphogenesis.

PMID- 15464571
TI  - Cranial sensory neuron development in the absence of brain-derived neurotrophic
      factor in BDNF/Bax double null mice.
AB  - To investigate the role of brain-derived neurotrophic factor (BDNF) in
      differentiation of cranial sensory neurons in vivo, we analyzed development of
      nodose (NG), petrosal (PG), and vestibular (VG) ganglion cells in genetically
      engineered mice carrying null mutations in the genes encoding BDNF and the
      proapoptotic Bcl-2 homolog Bax. In bax(-/-) mutants, ganglion cell numbers were
      increased significantly compared to wild-type animals, indicating that naturally
      occurring cell death in these ganglia is regulated by Bax signaling. Analysis of
      bdnf(-/-)bax(-/-) mutants revealed that, although the Bax null mutation
      completely rescued cell loss in the absence of BDNF, it did not rescue the
      lethality of the BDNF null phenotype. Moreover, despite rescue of BDNF-dependent
      neurons by the bax null mutation, sensory target innervation was abnormal in
      double null mutants. Vagal sensory innervation to baroreceptor regions of the
      cardiac outflow tract was completely absent, and the density of vestibular
      sensory innervation to the cristae organs was markedly decreased, compared to
      wild-type controls. Moreover, vestibular afferents failed to selectively
      innervate their hair cell targets within the cristae organs in the double
      mutants. These innervation failures occurred despite successful navigation of
      sensory fibers to the peripheral field, demonstrating that BDNF is required
      locally for afferent ingrowth into target tissues. In addition, the bax null
      mutation failed to rescue expression of the dopaminergic phenotype in a subset of
      NG and PG neurons. These data demonstrate that BDNF signaling is required not
      only to support survival of cranial sensory neurons, but also to regulate local
      growth of afferent fibers into target tissues and, in some cells, transmitter
      phenotypic expression is required.

PMID- 15464570
TI  - Rat kinesin light chain 3 associates with spermatid mitochondria.
AB  - We recently discovered that in rat spermatids, kinesin light chain KLC3 can
      associate with outer dense fibers, major sperm tail components, and accumulates
      in the sperm midpiece. Here, we show that mitochondria isolated from rat
      elongating spermatids have bound KLC3. Immunoelectron microscopy indicates that
      the association of KLC3 with mitochondria coincides with the stage in
      spermatogenesis when mitochondria move from the plasma membrane to the developing
      midpiece. KLC3 is able to bind in vitro to mitochondria from spermatids as well
      as somatic cells employing a conserved kinesin light chain motif, the tetratrico
      peptide repeats. Expression of KLC3 in fibroblasts results in formation of large
      KLC3 clusters close to the nucleus, which also contain mitochondria: no other
      organelles were present in these clusters. Mitochondria are not present in KLC3
      clusters after deletion of KLC3's tetratrico-peptide repeats. Our results
      indicate that the rat spermatid kinesin light chain KLC3 can associate with
      mitochondria.

PMID- 15464572
TI  - Spatiotemporal regulation of morphogenetic molecules during in vitro branching of
      the isolated ureteric bud: toward a model of branching through budding in the
      developing kidney.
AB  - In search of guiding principles involved in the branching of epithelial tubes in
      the developing kidney, we analyzed branching of the ureteric bud (UB) in whole
      kidney culture as well as in isolated UB culture independent of mesenchyme but in
      the presence of mesenchymally derived soluble factors. Microinjection of the UB
      lumen (both in the isolated UB and in the whole kidney) with fluorescently
      labeled dextran sulfate demonstrated that branching occurred via smooth tubular
      epithelial outpouches with a lumen continuous with that of the original
      structure. Epithelial cells within these outpouches cells were wedge-shaped with
      actin, myosin-2 and ezrin localized to the luminal side, raising the possibility
      of a "purse-string" mechanism. Electron microscopy and decoration of heparan
      sulfates with biotinylated FGF2 revealed that the basolateral surface of the
      cells remained intact, without the type of cytoplasmic extensions (invadopodia)
      that are seen in three-dimensional MDCK, mIMCD, and UB cell culture models of
      branching tubulogenesis. Several growth factor receptors (i.e., FGFR1, FGFR2, c
      Ret) and metalloproteases (i.e., MT1-MMP) were localized toward branching UB
      tips. A large survey of markers revealed the ER chaperone BiP to be highly
      expressed at UB tips, which, by electron microscopy, are enriched in rough
      endoplasmic reticulum and Golgi, supporting high activity in the synthesis of
      transmembrane and secretory proteins at UB tips. After early diffuse
      proliferation, proliferating and mitotic cells were mostly found within the
      branching ampullae, whereas apoptotic cells were mostly found in stalks. Gene
      array experiments, together with protein expression analysis by immunoblotting,
      revealed a differential spatiotemporal distribution of several proteins
      associated with epithelial maturation and polarization, including intercellular
      junctional proteins (e.g., ZO-1, claudin-3, E-cadherin) and the subapical
      cytoskeletal/microvillar protein ezrin. In addition, Ksp-cadherin was found at UB
      ampullary cells next to developing outpouches, suggesting a role in epithelial
      mesenchymal interactions. These data from the isolated UB culture system support
      a model where UB branching occurs through outpouching possibly mediated by wedge
      shaped cells created through an apical cytoskeletal purse-string mechanism.
      Additional potential mechanisms include (1) differential localization of growth
      factor receptors and metalloproteases at tips relative to stalks; (2) creation of
      a secretory epithelium, in part manifested by increased expression of the ER
      chaperone BiP, at tips relative to stalks; (3) after initial diffuse
      proliferation, coexistence of a balance of proliferation vs. apoptosis favoring
      tip growth with a very different balance in elongating stalks; and (4)
      differential maturation of the tight and adherens junctions as the structures
      develop. Because, without mesenchyme, both lateral and bifid branching occurs
      (including the ureter), the mesenchyme probably restricts lateral branching and
      provides guidance cues in vivo for directional branching and elongation as well
      as functioning to modulate tubular caliber and induce differentiation. Selective
      cadherin, claudin, and microvillar protein expression as the UB matures likely
      enables the formation of a tight, polarized differentiated epithelium. Although,
      in vivo, metanephric mesenchyme development occurs simultaneously with UB
      branching, these studies shed light on how (mesenchymally derived) soluble
      factors alone regulate spatial and temporal expression of morphogenetic molecules
      and processes (proliferation, apoptosis, etc.) postulated to be essential to the
      UB branching program as it forms an arborized structure with a continuous lumen.

PMID- 15464573
TI  - Maintenance of sister chromatid attachment in mouse eggs through maturation
      promoting factor activity.
AB  - Mammalian eggs naturally arrest at metaphase of the second meiotic division,
      until sperm triggers a series of Ca(2+) spikes that result in activation of the
      anaphase-promoting complex/cyclosome (APC/C). APC/C activation at metaphase
      targets destruction-box containing substrates, such as cyclin B1 and securin, for
      degradation, and as such eggs complete the second meiotic division. Cyclin B1
      degradation reduces maturation (M-phase)-promoting factor (MPF) activity and
      securin degradation allows sister chromatid separation. Here we examined the
      second meiotic division in mouse eggs following expression of a cyclin B1
      construct with an N-terminal 90 amino acid deletion (Delta 90 cyclin B1) that was
      visualized by coupling to EGFP. This cyclin construct was not an APC/C substrate,
      and so following fertilization, sperm were incapable of stimulating Delta 90
      cyclin B1 degradation. In these eggs, chromatin remained condensed and no
      pronuclei formed. As a consequence of the lack of pronucleus formation, sperm
      triggered Ca(2+) spiking continued indefinitely, consistent with a current model
      in which the sperm-activating factor is localized to the nucleus. Because Ca(2+)
      spiking was not inhibited by Delta 90 cyclin B1, the degradation timing of
      securin, visualized by coupling it to EGFP, was unaffected. However, despite
      rapid securin degradation, sister chromatids remained attached. This was a direct
      consequence of MPF activity because separation was induced following application
      of the MPF inhibitor roscovitine. Similar observations regarding the ability of
      MPF to prevent sister chromatid separation have recently been made in Xenopus egg
      extracts and in HeLa cells. The results presented here show this mechanism can
      also occur in intact mammalian eggs and further that this mechanism appears
      conserved among vertebrates. We present a model in which metaphase II arrest is
      maintained primarily by MPF levels only.

PMID- 15464574
TI  - Role of programmed cell death in patterning the Drosophila antennal arista.
AB  - Programmed cell death is a critical process for the patterning and sculpting of
      organs during development. The Drosophila arista, a feather-like structure at the
      tip of the antenna, is composed of a central core and several lateral branches. A
      homozygous viable mutation in the thread gene, which encodes an inhibitor of
      apoptosis protein, produces a branchless arista. We have found that mutations in
      the proapoptotic gene hid lead to numerous extra branches, suggesting that the
      level of cell death determines the number of branches in the arista. Consistent
      with this idea, we have found that thread mutants show excessive cell death
      restricted to the antennal imaginal disc during the middle third instar larval
      stage. These findings point to a narrow window of development in which regulation
      of programmed cell death is essential to the proper formation of the arista.

PMID- 15464575
TI  - Early requirement of the transcriptional activator Sox9 for neural crest
      specification in Xenopus.
AB  - The neural crest is a multipotent population of cells that arises at the neural
      plate border in the vertebrate embryo. We have previously shown that a member of
      the Sox family of transcription factors, Sox9, is a regulator of neural crest
      formation in Xenopus, as Sox9-depleted embryos failed to form neural crest
      progenitors. Here, we describe experiments that further investigate Sox9 function
      during neural crest development. Induction of neural crest progenitors in Xenopus
      is regulated by Wnt signaling. We show that this process is largely dependent on
      Sox9 function as Wnt-mediated neural crest induction is inhibited in the context
      of Sox9-depleted embryos. Moreover, we demonstrate that Sox9 functions as a
      transcriptional activator during neural crest formation. Expression of a
      construct in which Sox9 DNA-binding domain (HMG box) is fused to the repressor
      domain of Drosophila engrailed blocked neural crest formation, thereby mimicking
      the phenotype of Sox9-depleted embryos. Finally, using a hormone-inducible
      inhibitory mutant of Sox9, lacking the transactivation domain, we show that Sox9
      function is required for neural crest specification but not for its subsequent
      migration.

PMID- 15464576
TI  - The orphan COUP-TF nuclear receptors are markers for neurogenesis from cnidarians
      to vertebrates.
AB  - In bilaterians, COUP-TF nuclear receptors participate in neurogenesis and/or CNS
      patterning. In hydra, the nervous system is formed of sensory mechanoreceptor
      cells (nematocytes) and neuronal cells, both lineages deriving from a common stem
      cell. The hydra COUP-TF gene, hyCOUP-TF, which encodes highly conserved DNA
      binding and ligand-binding domains, belongs to the monophyletic COUP-TFs orphan
      receptor family (NR2F). In adult polyps, hyCOUP-TF is expressed in nematoblasts
      and a subset of neuronal cells. Comparative BrDU labeling analyses performed on
      cells expressing either hyCOUP-TF or the paired-like gene prdl-b showed that prdl
      b expression corresponded to early stages of proliferation, while hyCOUP-TF was
      detected slightly later. HyCOUP-TF and prdl-b expressing cells disappeared in sf
      1 mutants becoming "nerve-free". Moreover hyCOUP-TF and prdl-b expression was
      excluded from regions undergoing developmental processes. These data suggest that
      hyCOUP-TF and prdl-b belong to a genetic network that appeared together with
      neurogenesis during early metazoan evolution. The hyCOUP-TF protein specifically
      bound onto the evolutionarily conserved DR1 and DR5 response elements, and
      repressed transactivation induced by RAR:RXR nuclear receptors in a dose
      dependent manner when expressed in mammalian cells. Hence, a cnidarian
      transcription factor can be active in vertebrate cells, implying that functional
      interactions between COUP-TF and other nuclear receptors were evolutionarily
      conserved.

PMID- 15464577
TI  - Retinoic-acid-concentration-dependent acquisition of neural cell identity during
      in vitro differentiation of mouse embryonic stem cells.
AB  - Retinoic acid (RA) is one of the most important morphogens, and its embryonic
      distribution correlates with neural differentiation and positional specification
      in the developing central nervous system. To investigate the concentration
      dependent effects of RA on neural differentiation of mouse embryonic stem cells
      (ES cells), we investigated the precise expression profiles of neural and
      regional specific genes by ES cells aggregated into embryoid bodies (EBs) exposed
      to various concentrations of RA or the BMP antagonist Noggin. RA promoted both
      neural differentiation and caudalization in a concentration-dependent manner, and
      the concentration of RA was found to regulate dorso-ventral identity, i.e.,
      higher concentrations of RA induced a dorsal phenotype, and lower concentrations
      of RA induced a more ventral phenotype. The induction of the more ventral
      phenotype was due to the higher expression level of the N-terminus of sonic
      hedgehog protein (Shh-N) when treated with low concentration RA, as it was
      abrogated by an inhibitor of Shh signaling, cyclopamine. These findings suggest
      that the concentration of RA strictly and simultaneously regulates the
      neuralization and positional specification during differentiation of mouse ES
      cells and that it may be possible to use it to establish a strategy for
      controlling the identity of ES-cell-derived neural cells.

PMID- 15464578
TI  - Hedgehog signaling is required for commitment but not initial induction of slow
      muscle precursors.
AB  - In zebrafish, skeletal muscle precursors can adopt at least three distinct fates:
      fast, non-pioneer slow, or pioneer slow muscle fibers. Slow muscle fibers develop
      from adaxial cells and depend on Hedgehog signaling. We analyzed when precursors
      become committed to their fates and the step(s) along their differentiation
      pathway affected by Hedgehog. Unexpectedly, we find that embryos deficient in
      Hedgehog signaling still contain postmitotic adaxial cells that differentiate
      into fast muscle fibers instead of slow. We show that by the onset of
      gastrulation, slow and fast muscle precursors are already spatially segregated
      but uncommitted to their fates until much later, in the segmental plate when slow
      precursors become independent of Hedgehog. In contrast, pioneer and non-pioneer
      slow muscle precursors share a common lineage from the onset of gastrulation. Our
      results demonstrate that slow muscle precursors form independently of Hedgehog
      signaling and further provide direct evidence for a multipotent muscle precursor
      population whose commitment to the slow fate depends on Hedgehog at a late stage
      of development when postmitotic adaxial cells differentiate into slow muscle
      fibers.

PMID- 15464579
TI  - Maintenance of mouse trophoblast stem cell proliferation by TGF-beta/activin.
AB  - Mouse trophoblast stem (TS) cells can be grown indefinitely in vitro with FGF4
      and embryonic fibroblast conditioned media (EFCM). Here, we report that the
      active protein components of EFCM include TGF-beta and the related factor
      activin, and that long-term continuous TS cell proliferation is possible in media
      supplemented with only serum, FGF4, and TGF-beta. As trophoblasts are an
      epithelial cell type, the promotion of TS cell proliferation represents an
      unusual function for TGF-beta and activin since TGF-beta in particular is well
      known as an inhibitor of nontransformed epithelial cell proliferation. Our data
      suggest that constitutive FGF signaling in TS cells selectively inhibits the
      ability of TGF-beta to repress c-myc expression, a central component of the TGF
      beta cytostatic transcriptional response previously observed to be lost in other
      epithelial cell types upon oncogenic Ras transformation.

PMID- 15464580
TI  - Increased sensitivity and clustering of elementary Ca2+ release events during
      oocyte maturation.
AB  - The universal signal for egg activation at fertilization is a rise in cytoplasmic
      Ca(2+) with defined spatial and temporal kinetics. Mammalian and amphibian eggs
      acquire the ability to produce such Ca(2+) signals during a maturation period
      that precedes fertilization and encompasses resumption of meiosis and progression
      to metaphase II. In Xenopus, immature oocytes produce fast, saltatory Ca(2+)
      waves that can be oscillatory in nature in response to IP(3). In contrast, mature
      eggs produce a single continuous, sweeping Ca(2+) wave in response to IP(3) or
      sperm fusion. The mechanisms mediating the differentiation of Ca(2+) signaling
      during oocyte maturation are not well understood. Here, I characterized
      elementary Ca(2+) release events (Ca(2+) puffs) in oocytes and eggs and show that
      the sensitivity of IP(3)-dependent Ca(2+) release is greatly enhanced during
      oocyte maturation. Furthermore, Ca(2+) puffs in eggs have a larger spatial
      fingerprint, yet are short lived compared to oocyte puffs. Most interestingly,
      Ca(2+) puffs cluster during oocyte maturation resulting in a continuum of Ca(2+)
      release sites over space in eggs. These changes in the spatial distribution of
      elementary Ca(2+) release events during oocyte maturation explain the continuous
      nature and slower speed of the fertilization Ca(2+) wave.

PMID- 15464581
TI  - Rho-associated kinases play a role in endocardial cell differentiation and
      migration.
AB  - Development of the endocardial cushions in the heart involves cell migration and
      cell differentiation, which is known as epithelial-mesenchymal transformation
      (EMT). These processes are regulated by cell signaling systems. Yet, the roles of
      intracellular GTPases and their effectors on these cellular activities remain to
      be addressed. This study investigated the role Rho GTPase-associated kinases
      (ROCKs) in endocardial cushion development. Using reverse transcription (RT) and
      polymerase chain reaction (PCR), expression of the rock1 and rock2 genes was
      found in the endocardial cushions during development. To investigate the role of
      ROCKs in development, the ROCK inhibitor Y27632 and adenoviruses containing a
      dominant negative form of the rock gene were used to treat cultured endocardial
      cushions and cells. In monolayer cell culture and three-dimensional tissue
      culture, blockade of ROCK inhibited EMT development. Using three-dimensional
      collagen gel assays and confocal microscopy, we also observed inhibition of cell
      migration with ROCK inhibition. Examination of cell morphology and actin
      cytoskeleton revealed that inhibition of ROCK activity disturbed cytoskeletal
      organization and blocked the formation of lamellipodia and filopodia.
      Collectively, these data show that ROCKs play an essential role in endothelial
      cell differentiation and migration during endocardial cushion development.

PMID- 15464582
TI  - At most three ES cells contribute to the somatic lineages of chimeric mice and of
      mice produced by ES-tetraploid complementation.
AB  - Chimeric or entirely embryonic stem (ES) cell-derived mice ("ES mice") can be
      produced by injecting ES cells into diploid (2n) or tetraploid (4n) host
      blastocysts, respectively. Usually, between 10 and 15 ES cells are injected into
      the host blastocyst, but it is not clear how many of the injected cells
      contribute to the somatic lineages, thus serve as "founder cells" of the embryo
      proper. We have used genetically labeled ES cells to retrospectively determine
      the number of founder ES cells that generate the somatic lineages of chimeric and
      of ES mice. ES cell clones individually labeled with provirus were mixed in equal
      numbers and injected into 2n or 4n blastocysts to generate chimeric or ES mice.
      Southern analysis of DNA from the resulting animals indicated that the somatic
      lineages were most often derived from one or two and sometimes from up to three
      founder ES cells. The number of founder cells was independent of the total number
      of cells injected into the host blastocysts. Our results are consistent with the
      notion that constraints of the host embryo restrict the number of ES cells that
      can contribute to a chimeric or an ES mouse.

PMID- 15464583
TI  - Inhibition of integrin-mediated adhesion and signaling disrupts retinal
      development.
AB  - Integrins are the major family of cell adhesion receptors that mediate cell
      adhesion to the extracellular matrix (ECM). Integrin-mediated adhesion and
      signaling play essential roles in neural development. In this study, we have used
      echistatin, an RGD-containing short monomeric disintegrin, to investigate the
      role of integrin-mediated adhesion and signaling during retinal development in
      Xenopus. Application of echistatin to Xenopus retinal-derived XR1 glial cells
      inhibited the three stages of integrin-mediated adhesion: cell attachment, cell
      spreading, and formation of focal adhesions and stress fibers. XR1 cell
      attachment and spreading increased tyrosine phosphorylation of paxillin, a focal
      adhesion associated protein, while echistatin significantly decreased
      phosphorylation levels of paxillin. Application of echistatin or beta(1) integrin
      function blocking antibody to the embryonic Xenopus retina disrupted retinal
      lamination and produced rosette structures with ectopic photoreceptors in the
      outer retina. These results indicate that integrin-mediated cell-ECM interactions
      play a critical role in cell adhesion, migration, and morphogenesis during
      vertebrate retinal development.

PMID- 15464584
TI  - Totipotent migratory stem cells in a hydroid.
AB  - Hydroids, members of the most ancient eumetazoan phylum, the Cnidaria, harbor
      multipotent, migratory stem cells lodged in interstitial spaces of epithelial
      cells and are therefore referred to as interstitial cells or i-cells. According
      to traditional understanding, based on studies in Hydra, these i-cells give rise
      to several cell types such as stinging cells, nerve cells, and germ cells, but
      not to ectodermal and endodermal epithelial cells; these are considered to
      constitute separate cell lineages. We show here that, in Hydractinia, the
      developmental potential of these migratory stem cells is wider than previously
      anticipated. We eliminated the i-cells from subcloned wild-type animals and
      subsequently introduced i-cells from mutant clones and vice versa. The mutant
      donors and the wild-type recipients differed in their sex, growth pattern, and
      morphology. With time, the recipient underwent a complete conversion into the
      phenotype and genotype of the donor. Thus, under these experimental conditions
      the interstitial stem cells of Hydractinia exhibit totipotency.

PMID- 15464585
TI  - Pur alpha and Sp8 as opposing regulators of neural gata2 expression.
AB  - Gata2 is an essential hematopoietic transcriptional factor that is also expressed
      prominently in the nervous system. The early lethality of knockout mice due to
      severe anemia has largely precluded studies of gata2 neural regulation and
      function. In this report, we describe the identification of zebrafish Pur alpha
      and Sp8 orthologs as two factors that function to regulate neuronal expression of
      gata2. During embryogenesis, Pur alpha is expressed widely, whereas Sp8 has an
      overlapping pattern of expression with gata2 in the nervous system. Knockdown and
      ectopic expressions of Pur alpha and Sp8 indicate that these factors function,
      respectively, as a repressor and an activator of gata2 gene expression in the
      nervous system. With consideration given to the previously established roles for
      these factors, we propose a model for how the transcriptional regulation of
      neural gata2 expression may be involved in controlling cellular proliferation in
      the nervous system.

PMID- 15464586
TI  - GATA4 is a dosage-sensitive regulator of cardiac morphogenesis.
AB  - Normal heart development is orchestrated by a set of highly conserved
      transcription factors that includes GATA4, Nkx2-5, and Tbx5. Heterozygous
      mutation of each of these genes causes congenital heart disease in humans. In
      mouse models, haploinsufficiency for Nkx2-5 or Tbx5 resulted in an increased
      incidence of structural heart disease, confirming that normal heart development
      is sensitive to small changes in expression levels of Nkx2-5 and Tbx5. However,
      mice haploinsufficient for GATA4 have not been reported to have cardiac
      abnormalities. We generated two new GATA4 alleles, GATA4(H) and GATA4(flox).
      GATA4(flox/flox) embryos expressed 50% less GATA4 protein in the heart and
      survived normally. In contrast, GATA4(H/H) embryos expressed 70% less GATA4
      protein in the heart and died between days 13.5 and 16.5 of gestation. These
      embryos had common atrioventricular canal (CAVC), double outlet right ventricle
      (DORV), hypoplastic ventricular myocardium, and normal coronary vasculature.
      Myocardial hypoplasia was associated with diminished cardiomyocyte proliferation.
      Hemodynamic measurements demonstrated that these embryos had normal systolic
      function, severe diastolic dysfunction, and atrioventricular regurgitation.
      Surprisingly, expression levels of the putative GATA4 target genes ANF, BNP,
      MEF2C, Nkx2-5, cyclin D2, and BMP4 were unchanged in mutant hearts, suggesting
      that GATA4 is not a dose-limiting regulator of the expression of these genes
      during later stages of embryonic cardiac development. These data demonstrate that
      multiple aspects of embryonic cardiac morphogenesis and function are exquisitely
      sensitive to small changes in GATA4 expression levels.

PMID- 15464587
TI  - The Drosophila transmembrane protein Fear-of-intimacy controls glial cell
      migration.
AB  - Development of complex organs depends on intensive cell-cell interactions, which
      help coordinate movements of many cell types. In a genetic screen aimed to
      identify genes controlling midline glia migration in the Drosophila nervous
      system, we have identified mutations in the gene kastchen. Here we show that
      during embryogenesis kastchen is also required for the normal migration of
      longitudinal and peripheral glial cells. During larval development, kastchen non
      cell autonomously affects the migration of the subretinal glia into the eye disc.
      During embryonic development, kastchen not only affects glial cell migration but
      also controls the migration of muscle cells toward their attachment sites. In all
      cases, kastchen apparently functions in terminating or restricting cell
      migration. We identified the molecular nature of the gene by performing
      transgenic rescue experiments and by sequence analysis of mutant alleles.
      Kastchen corresponds to the recently described gene fear-of-intimacy (foi) that
      was identified in screen for genes affecting germ cell migration, suggesting that
      Foi-Kastchen is more generally involved in regulating cell migration. It encodes
      a member of an eight-transmembrane domain protein family of putative Zinc
      transporters or proteases. We determined the topology of the Foi protein by using
      antisera against luminal and intracellular domains of the protein and provide
      evidence that it does not act as a Zinc transporter. Genetic evidence suggests
      that one of the functions of foi may be associated with hedgehog signaling.

PMID- 15464588
TI  - XSIP1 is essential for early neural gene expression and neural differentiation by
      suppression of BMP signaling.
AB  - Neural differentiation is induced by inhibition of BMP signaling. Secreted
      inhibitors of BMP such as Chordin from the Spemann organizer contribute to the
      initial step of neural induction. Xenopus Smad-interacting protein-1 gene (XSIP1)
      is expressed in neuroectoderm from the early gastrula stage through to the
      neurula stage. XSIP1 is able to inhibit BMP signaling and overexpression of XSIP1
      induces neural differentiation. To clarify the function of XSIP1 in neural
      differentiation, we performed a loss-of-function study of XSIP1. Knockdown of
      XSIP1 inhibited SoxD expression and neural differentiation. These results
      indicate that XSIP1 is essential for neural induction. Furthermore, loss-of
      function experiments showed that SoxD is essential for XSIP1 transcription and
      for neural differentiation. However, inhibition of XSIP1 translation prevented
      neural differentiation induced by SoxD; thus, SoxD was not sufficient to mediate
      neural differentiation. Expression of XSIP1 was also required for inhibition of
      BMP signaling. Together, these results suggest that XSIP1 and SoxD
      interdependently function to maintain neural differentiation.

PMID- 15464589
TI  - The clinical relevance of adrenomedullin: a promising profile?
AB  - Adrenomedullin (AM) is a peptide that possesses potentially beneficial
      properties. Since the initial discovery of the peptide by Kitamura et al. in
      1993, the literature has been awash with reports describing its novel mechanisms
      of action and huge potential as a therapeutic target. Strong evidence now exists
      that AM is able to act as an autocrine, paracrine, or endocrine mediator in a
      number of biologically significant functions, including the endothelial
      regulation of blood pressure, protection against organ damage in sepsis or
      hypoxia, and the control of blood volume through the regulation of thirst. Its
      early promise as a potential mediator/modulator of disease was not, however,
      entirely as a result of the discovery of physiological functions but due more to
      the observation of increasing levels measured in plasma in direct correlation
      with disease progression. In health, AM circulates at low picomolar
      concentrations in plasma in 2 forms, a mature 52-amino acid peptide and an
      immature 53-amino acid peptide. Plasma levels of AM have now been shown to be
      increased in a number of pathological states, including congestive heart failure,
      sepsis, essential hypertension, acute myocardial infarction, and renal
      impairment. These earliest associations have been further supplemented with
      evidence of a role for AM in other pathologies including, most intriguingly,
      cancer. In this review, we offer a timely review of our current knowledge on AM
      and give a detailed account of the putative role of AM in those clinical areas in
      which the best therapeutic opportunities might exist.

PMID- 15464590
TI  - GPCR interacting proteins (GIP).
AB  - G protein-coupled receptors (GPCR) interact not only with heterotrimeric G
      proteins but also with accessory proteins called GPCR interacting proteins (GIP).
      These proteins have important functions. They are implicated in GPCR targeting to
      specific cellular compartments, in their assembling into large functional
      complexes called "receptosomes," in their trafficking to and from the plasma
      membrane, and in the fine-tuning of their signaling properties. There are several
      types of GIPs. Some are transmembrane proteins such as another GPCR
      (homodimerization and heterodimerization), ionic channels, ionotropic receptors,
      and single transmembrane proteins. The latter is implicated in the fine-tuning of
      receptor pharmacology or signaling. Other GIPs are soluble proteins interacting
      mainly with the "magic" C-terminal tail. Among them, PDZ domain-containing
      proteins are the most abundant. They generally, but not always, interact with the
      extreme C-terminal domain of GPCRs. Some GIPs interact with specific sequences of
      the C-terminal such as the Homer binding sequence (-PPxxFR-), the dopamine
      receptor interacting protein (DRIP) binding sequence (-FxxxFxxxF-), etc. Finally,
      only few GIPs have been found thus far to interact with the third intracellular
      loop of GPCRs. The future will tell us if this situation is only due to technical
      reasons.

PMID- 15464591
TI  - Emerging roles of urotensin-II in cardiovascular disease.
AB  - Urotensin-II (UII) is a highly potent endogenous peptide within the
      cardiovascular system. Through stimulation of Galphaq-coupled UT receptors, UII
      mediates contraction of vascular smooth muscle and endothelial-dependent
      vasorelaxation, and positive inotropy in human right atrium and ventricle. A
      pathogenic role of the UT receptor system is emerging in cardiovascular disease
      states, with evidence for up-regulation of the UT receptor system in patients
      with congestive heart failure (CHF), pulmonary hypertension, cirrhosis and portal
      hypertension, and chronic renal failure. In vitro and in vivo studies show that
      under pathophysiological conditions, UII might contribute to cardiomyocyte
      hypertrophy, extracellular matrix production, enhanced vasoconstriction, vascular
      smooth muscle cell hyperplasia, and endothelial cell hyper-permeability. Single
      nucleotide polymorphisms of the UII gene may also impart a genetic predisposition
      of patients to diabetes. Therefore, the UT receptor system is a potential
      therapeutic target in the treatment of cardiac, pulmonary, and renal diseases. UT
      receptor antagonists are currently being developed to prevent and/or reverse the
      effects of over-activated UT receptors by the endogenous ligand. This review
      describes UII peptide and converting enzymes, and UT receptors in the
      cardiovascular system, focusing on pathophysiological roles of UII in the heart
      and blood vessels.

PMID- 15464592
TI  - Novel functions of proteins encoded by viral stress-inducible genes.
AB  - The interferon (IFN) system is the first line of defense against viral infection
      in vertebrates. It is well known that IFN synthesis is induced by viral infection
      and secreted IFN act upon as yet uninfected neighboring cells to prepare them for
      combating oncoming virus infection. The products of IFN-stimulated genes (ISG),
      which number in hundreds, mediate this antiviral action of IFN. Recent evidence
      suggests that many of these genes are also induced directly by double-stranded
      RNA (dsRNA), a common byproduct of virus infection, or by other viral products.
      We refer to this family of genes, on which this article is focused, as viral
      stress-inducible genes (VSIG). First, we will discuss the different signaling
      pathways that lead to induce transcription of these genes in response to
      different agents. Second, we will review the available information about the
      inducibility of different VSIG by IFN, dsRNA, and viruses. In this article, we
      will review the functions of proteins encoded by selected members of the VSIG
      family. Because most of these proteins affect many aspects of cellular
      physiology, the information presented here is important for understanding not
      only the nature of host response to virus infection but also cellular responses
      to cytokines, such as IFN and exogenous dsRNA, which is known to signal through
      Toll-like receptor 3 (TLR3). Finally, we will present a future perspective and
      point out the main gaps of our knowledge in the field.

PMID- 15464593
TI  - Cloning and overexpression of the old yellow enzyme gene of Candida
      macedoniensis, and its application to the production of a chiral compound.
AB  - The gene encoding old yellow enzyme (OYE), which catalyzes the conversion of
      ketoisophorone (KIP; 2,6,6-trimethyl-2-cyclohexen-1,4-dione) to (6R)-levodione
      (2,2,6-trimethylcyclohexane-1,4-dione), of Candida macedoniensis was cloned and
      sequenced. A 1212bp nucleotide fragment (oye) was confirmed to be the gene
      encoding OYE based on the agreement of internal amino acid sequences. Oye encodes
      a total 403 amino acid residues, and the deduced amino acid sequence shows a high
      degree of similarity to those of other microbial OYE family proteins. An
      expression vector, pETOYE, that contains the full length of oye was constructed.
      Escherichia coli harboring pETOYE exhibited an about six-fold increase in
      specific KIP-reducing activity under the control of the T7 promoter as compared
      with that of C. macedoniensis. (6R)-Levodione formed with washed cells of the
      transformant and a cofactor regeneration system amounted to 638 mM (98.2 mg ml(
      1)), the a molar yield being 96.9%. The asymmetric reduction of KIP to (6R)
      levodione with E. coli cells, which co-expressed both oye and the glucose
      dehydrogenase gene (gdh), as a catalyst was investigated. The (6R)-levodione
      formed amounted to 627 mM (96.6 mg ml(-1)), the a molar yield being 95.4%. Since
      the use of E. coli BL21 (DE3) cells co-expressing oye and gdh as a catalyst is
      simple and does not require the addition of glucose dehydrogenase, it is highly
      advantageous for the practical synthesis of (6R)-levodione.

PMID- 15464594
TI  - Escherichia coli detection by GFP-labeled lysozyme-inactivated T4 bacteriophage.
AB  - Escherichia coli has been used as an indicator of the fecal contamination of
      water and food, identifying potential health hazards. In this study, an E. coli
      specific bacteriophage, T4, was used to detect E. coli bacteria. The T4 phage
      small outer capsid (SOC) protein was used to present green fluorescent protein
      (GFP), an easily detectable marker protein, on the phage capsid. To inactivate
      phage lytic activity, we used the T4e(-) phage, which does not produce the
      lysozyme responsible for host cell lysis. Infection of E. coli K12 cells with the
      GFP-labeled T4e(-) phage (T4e(-)/GFP) enabled the visualization and distinction
      of E. coli K12 cells from T4 phage-insensitive cells, Pseudomonas aeruginosa.
      Prolonged incubation of E. coli K12 cells with the T4e(-)/GFP phage did not lead
      to cell lysis. Propagation of T4e(-)/GFP in host cells increased the intensity of
      green fluorescence, making the distinction of E. coli cells from other cells
      simple and effective. This method enables the rapid, conclusive quantitation of
      E. coli cells within an hour.

PMID- 15464595
TI  - Amino-terminal anchored surface display in insect cells and budded baculovirus
      using the amino-terminal end of neuraminidase.
AB  - Methods currently used for surface display on insect cells and budded
      baculovirus, all utilize the sequences from class I transmembrane proteins. This
      gives rise to some problems when handling unknown genes or cDNAs encoding full
      length proteins. First, the stop codon from the cloned gene will be located
      upstream of the sequence for the transmembrane region. Second, the chance of
      getting the sequences encoding the signal peptide and the transmembrane region in
      frame with the cloned gene is small. To minimize these problems, we here present
      a method by which cDNAs or genes of interest can be cloned and fused to the
      codons for the signal peptide and transmembrane region of neuraminidase (NA), a
      class II transmembrane protein of the influenza virus. By placing both the signal
      peptide and transmembrane region at the amino-terminal, potential problems
      regarding stop codons are eliminated and errors in frame-shift minimized. To
      obtain proof of principle, the gene encoding enhanced green fluorescent protein,
      EGFP, was subcloned into a shuttle vector downstream of the neuraminidase
      sequence and the fusion product was then transferred to a baculovirus vector and
      transfected into insect cells (Sf9). Using this method, EGFP was found to be
      expressed on the surface of both infected cells and budded virus in an accessible
      manner.

PMID- 15464596
TI  - A diffusion-reaction model for DNA microarray assays.
AB  - DNA microarrays are extensively used for the quantification of the degree of
      differential mRNA expression. The assay involves hybridization of mobile DNA
      strands with immobilized complementary DNA strands to form duplexes. The overall
      duplex formation rate depends on the rate of transport of strands in solution to
      the corresponding spot on the surface, and the rate of the hybridization
      reaction. We present a theoretical model that incorporates both kinetics of the
      reversible hybridization reaction and diffusional transport of the labeled
      strands, and analyze DNA microarray hybridization using this model. Simulations
      are carried out in a geometrically realistic domain for labeled DNA
      concentrations corresponding to rare and abundant transcripts for typical assay
      conditions. The rate of strand diffusion in solution is shown to strongly affect
      the overall hybridization rate. We compute the minimum inter-spot spacing for
      replicate spots to enhance sensitivity. We also determine the hybridization time
      for which reliable estimates of the relative mRNA abundance of two species can be
      obtained using total fluorescence intensities. An analytical solution for the
      concentration distribution of mobile strands at intermediate hybridization times
      provides a convenient tool to calculate the mobile strand concentration profiles.
      This model provides a framework for the process analysis of all microarray assays
      currently used for genomic transcriptional analysis.

PMID- 15464597
TI  - Entropy production mapping on stretched DNA interacted with proteins.
AB  - This paper presents an entropy production mapping (EPM) method for detecting a
      higher-order structure change of a stretched and immobilized DNA molecule on a
      cover slip through measuring and mapping an increment of the orientational
      entropy (defined as "entropy production") of the Watson-Crick base pairs by the
      interaction of biological factors such as proteins; the stretched DNA molecule
      undergoes a higher-order structure change by the interaction, so that the
      orientational entropy at the interaction regions increases because the alignment
      of the base pairs is reduced at the regions. We demonstrated the utility of this
      "EPM method" by using a histone-lambda DNA system. It is revealed that the
      histone interaction region is clearly distinguished from no interaction regions
      on a stretched lambda DNA molecule immobilized on a cover slip.

PMID- 15464598
TI  - Efficient isolation of cDNA clones encoding rheumatoid arthritis autoantigens by
      lambda phage surface display.
AB  - Bacteriophage lambda surface display was used to isolate cDNA clones encoding
      autoantigens recognized by synovial fluid (SF) or sera from patients with
      rheumatoid arthritis (RA). We constructed cDNA libraries from human synovial
      sarcoma cells and synovial tissue, using the surface display vector lambdafoo.
      The cDNA libraries were screened by affinity selection using 40 SF and 44 sera as
      probes separately immobilized in microtiter wells. Phage clones isolated encode
      13 different autoantigens; an unknown protein, two proteins previously unanalyzed
      as autoimmune antigens, three proteins previously unknown to be recognized by RA
      sera, and seven known RA antigens. When analyzed their sensitivity and
      specificity for RA by phage enzyme-linked immunosorbent assay, frequencies of
      sera that recognize the newly-isolated autoantigens ranged from 20.5 to 6.8% of a
      panel of RA sera, and 13.6-0% of other autoimmune disease sera. These results
      indicate that the lambda phage surface display may be powerful for the isolation
      of cDNA clones encoding autoantigens recognized by SF or sera from patients with
      not only RA but also other autoimmune diseases.

PMID- 15464599
TI  - High-throughput S-SAP by fluorescent multiplex PCR and capillary electrophoresis
      in plants.
AB  - The inherent replicative mode of transposition endows retrotransposons with
      considerable advantages as genetic tools in plant genome analysis. Here we
      present a high-throughput sequence-specific amplification polymorphism (S-SAP)
      method based on copia-like retrotransposons to fulfill the increasing desire of
      screening large numbers of samples in plants. Classic approach for digestion,
      ligation and pre-amplification was combined with optimized fluorescent multiplex
      PCR for simultaneously selective amplifying S-SAP fragments, and multiple S-SAPs
      were subsequently detected by capillary electrophoresis using ABI PRISM 3700
      capillary instruments. Comparisons of results from multiplex PCR with simplex
      PCR, and from capillary electrophoresis with slab-gel electrophoresis
      demonstrated that this method is an efficient, economical, and accurate means for
      high-throughput and large-scale genotyping retrotransposon variation in plants.

PMID- 15464600
TI  - Molecular cloning and expression in yeast of caprine prochymosin.
AB  - We cloned and characterized a preprochymosin cDNA from the abomasum of milk-fed
      kid goats. This cDNA contained an open reading frame that predicts a polypeptide
      of 381 amino acid residues, with a signal peptide and a proenzyme region of 16
      and 42 amino acids, respectively. Comparison of the caprine preprochymosin
      sequence with the corresponding sequences of lamb and calf revealed 99 and 94%
      identity at the amino acid level. The cDNA fragment encoding the mature portion
      of caprine prochymosin was fused in frame both to the killer toxin signal
      sequence and to the alpha-factor signal sequence-FLAG in two different yeast
      expression vectors. The recombinant plasmids were transformed into Kluyveromyces
      lactis and Saccharomyces cerevisiae cells, respectively. Culture supernatants of
      both yeast transformants showed milk-clotting activity after activation at acid
      pH. The FLAG-prochymosin fusion was purified from S. cerevisiae culture
      supernatants by affinity chromatography. Proteolytic activity assayed toward
      casein fractions indicated that the recombinant caprine chymosin specifically
      hydrolysed kappa-casein.

PMID- 15464601
TI  - Cephamycin C production is regulated by relA and rsh genes in Streptomyces
      clavuligerus ATCC27064.
AB  - The effects of growth rate and nutrient uptake rate on the production of
      cephamycin C were determined in the parental strain, deltarelA mutant, and
      deltarsh null mutant of S. clavuligerus. Production of cephamycin C was inversely
      related to mycelium growth and the phosphate feed rate was more critical for the
      production of cephamycin C. On the contrary, the production of cephamycin C was
      completely abolished in the deltarelA mutant, but not in deltarsh mutant. The
      changes in the cephamycin C production by disruption of the relA and rsh genes
      are presumably associated with the consequent ability of the mutants to
      accumulate (p)ppGpp under nutrient starvation. Therefore, it is concluded that
      the stringent response of S. clavuligerus to starvation for nutrients is governed
      mainly by RelA rather than Rsh and that the response is more apparently regulated
      by the limitation of phosphate.

PMID- 15464602
TI  - Adenoviral vector mediates high expression levels of human growth hormone in the
      milk of mice and goats.
AB  - The production of large quantities of complex proteins with biopharmaceutical
      purposes is the main drawback for their more extensive use. Here we demonstrated
      that a direct instillation of a recombinant adenoviral vector containing an
      expression cassette for the human growth hormone gene into the mammary gland of
      mice and goats allowed for the efficient secretion of human growth hormone in the
      milk. Through this approach we were able to express human growth hormone at
      maximal levels of 2.8 mg/ml in the milk of mice and up to 0.3 mg/ml in goat milk.
      We found that the expression levels were closely dependent on both the degree of
      differentiation of the secretory epithelium and on the adenoviral dose used. Here
      we demonstrated that the direct transduction of mammary epithelial cells by means
      of a recombinant adenovirus could be a suitable alternative to transgenic
      technology for the production of recombinant proteins of biopharmaceutical
      interest.

PMID- 15464603
TI  - Overexpression and affinity chromatography purification of the Type III
      restriction endonuclease EcoP15I for use in transcriptome analysis.
AB  - The Type III restriction endonuclease EcoP15I is a multifunctional hetero
      oligomeric enzyme that recognizes the non-symmetric DNA sequence 5'-CAGCAG. For
      efficient cleavage, EcoP15I needs the interaction with two copies of the
      recognition sequence that have to be inversely oriented in the DNA double strand.
      The enzyme cuts the upper DNA strand 25-26 bp and the lower DNA strand 27-28 bp,
      respectively, downstream of the recognition sequence-a distinct feature that
      makes the enzyme particularly valuable for gene expression profiling methods
      relying on the SAGE procedure (Matsumura et al., PNAS 100, 15718, 2003). Because
      the broader use of this transcriptome analysis method requires the availability
      of larger amounts of restriction endonuclease EcoP15I and the enzyme is not
      commercially available, we have cloned the genes coding for the EcoP15I
      restriction endonuclease into pQE-16 plasmid vector that provides the enzyme with
      a C-terminal 6xHis-tag. After Ni-NTA affinity chromatography and ion exchange
      chromatography on heparin sepharose, we obtained 5mg homogeneous EcoP15I per gram
      cell pellet within 1-2 day(s). Moreover, the C-terminally 6xHis-tagged EcoP15I
      restriction endonuclease shows comparable enzymatic activity as the untagged
      enzyme.

PMID- 15464604
TI  - Gene expression profiling of Escherichia coli expressing double Vitreoscilla
      haemoglobin.
AB  - In a recent investigation, expression of a double Vitreoscilla haemoglobin (two
      fused VHb molecules) in Escherichia coli grown in shake flasks resulted in higher
      final cell density and considerably higher levels of ribosomes and tRNA. In this
      study, we have investigated the E. coli transcriptome in cells expressing native
      VHb, double VHb and control cells lacking VHb by hybridising mRNA from the
      different constructs to high-density oligonucleotide arrays. Within the 95%
      confidence interval, 4 and 5% of all detected genes in native VHb cells were up-
      and down-regulated, respectively; in double VHb cells the corresponding numbers
      were 6 and 10%, respectively. Dividing the data into different functional groups
      revealed that genes involved in energy metabolism, central intermediary
      metabolism and cell processes were the most affected at the mRNA level.
      Particularly, the up-regulation of genes involved in translation and
      posttranslational modification observed in double VHb cells demonstrates a strong
      relationship between the regulation of ribosomal genes and the actual number of
      ribosomes.

PMID- 15464605
TI  - Peptidylpropyl isomerase B (PPIB): a suitable reference gene for mRNA
      quantification in peripheral whole blood.
AB  - Quantitative real-time RT-PCR is a very powerful technique for measuring gene
      expression at the mRNA level. In order to compare mRNA expression in different
      experimental or clinical conditions, expression of a target gene has to be
      normalized to an appropriate internal standard, which is generally a housekeeping
      gene. In our study, we have tested several housekeeping genes in peripheral whole
      blood of healthy volunteers and patients suffering from inflammatory diseases. A
      first analysis of 91 samples illustrated that the mRNA expression of
      peptidylpropyl isomerase B (PPIB) encoding for cyclophilin B protein, is more
      stable than beta actin and glyceraldehyde-3-phosphate dehydrogenase, which are
      both commonly selected as internal standard. Among the three genes tested, beta
      actin displayed the highest inter-sample variation of expression. The constancy
      of PPIB mRNA expression was further confirmed by 214 additional samples. In
      conclusion, we showed that PPIB, in contrast to beta actin and glyceraldehyde-3
      phosphate dehydrogenase, is a suitable housekeeping gene in human peripheral
      blood.

PMID- 15464606
TI  - Transglycosylation reaction of xylanase B from the hyperthermophilic Thermotoga
      maritima with the ability of synthesis of tertiary alkyl beta-D-xylobiosides and
      xylosides.
AB  - The recombinant xylanase B (XynB) of Thermotoga maritima MSB8 was characterized
      and was found to cleave p-nitrophenyl beta-D-xyloside via the transglycosylation
      reaction in the previous study. XynB was activated in the presence of alcohols,
      and XynB activity was increased by iso-propanol (2M) to 2.1-fold. This type of
      activation was investigated and was shown to be due to the transglycosylation
      activity with p-nitrophenyl beta-D-xylobioside being converted to alkyl beta-D
      xylobiosides in the presence of XynB and alcohols. Through the transglycosylation
      reaction, alkyl beta-xylosides and xylobiosides were simultaneously produced in
      the presence of xylan and alcohols. Primary alcohols were found to be the best
      acceptors. The highest yields of alkyl beta-xylosides and xylobiosides were 33%
      and 50% of the total sugar, respectively. XynB showed a great ability to transfer
      xylose and xylobiose to secondary alcohol acceptors, and was unique for being
      able to synthesize the tertiary alkyl beta-xylosides and xylobiosides with high
      yields of 18.2% and 11.6% of the total sugar, respectively. This is the first
      report of a xylanase with the ability to synthesize tertiary alkyl beta-xylosides
      and xylobiosides. The specificity of the beta-linkage was confirmed by the proton
      nuclear magnetic resonance ((1)H NMR). Thus, XynB of T. maritima appears to be an
      ideal enzyme for the synthesis of useful alkyl beta-xylosides and xylobiosides.

PMID- 15464607
TI  - Refolding kinetics of denatured-reduced lysozyme in the presence of folding aids.
AB  - The refolding kinetic behavior of denatured-reduced lysozyme in the presence of
      folding aids (acetamide, acetone, thiourea, L-arginine or glycerol) was studied
      utilizing a simplified model describing the competition between first-order
      folding reaction and third-order aggregation. It was found that the protein
      folding aids could be categorized into two groups. One of them at proper
      concentrations, such as acetamide, acetone, thiourea and L-arginine, stabilized
      unfolded protein or folding intermediates. In the presence of these additives,
      the folding rate decreased with increasing their concentration, and there existed
      a concentration where the aggregation rate constant was minimized. So, there was
      an optimum concentration for the folding aids to produce a high yield. The other
      group was protein stabilizers such as glycerol. In the presence of this kind of
      folding aids, both the refolding rate and yield were enhanced by increasing their
      concentration to a proper value. Moreover, their effect on improving protein
      refolding was additive to those of the first group. So the cooperative
      application of the two kinds of folding aids could result in favorable refolding
      rate and yield of protein.

PMID- 15464608
TI  - The effect of light intensity on hydrogen production by sulfur-deprived
      Chlamydomonas reinhardtii.
AB  - The effect of light intensity on hydrogen production by sulfur-deprived
      Chlamydomonas reinhardtii was studied in situ using either long- or short-term
      experiments, or alternatively, with samples withdrawn from the photobioreactor.
      Overall hydrogen production by S-deprived culture was shown to depend on the
      light intensity and to exhibit regions of light limitation and light inhibition.
      The optimal incident light intensity for hydrogen production was independent of
      the method of sulfur deprivation or the initial acetate concentration in the
      medium (12-34 mM). However, it varied with the Chl concentration and the
      thickness of the photobioreactor. To calculate the average light intensity in the
      photobioreactor under different experimental conditions, a special mathematics
      approach was developed. The optimal average light intensity for H(2) production
      appeared to be 30-40 microE m(-2)s(-1) and was independent of the Chl or acetate
      concentrations and the method of S deprivation. The inhibitory effect of high
      light intensity was related to the enhanced O(2) evolution activity during the
      photosynthetic stage of sulfur deprivation and to the high activity of
      photosystem II at the beginning of the H(2)-production phase. Data support the
      major role of photosystem II in supplying reductants through photosystem I to the
      hydrogenase throughout the H(2)-production phase.

PMID- 15464609
TI  - Links between morphology and physiology of Ganoderma lucidum in submerged culture
      for the production of exopolysaccharide.
AB  - Ganoderma lucidum was grown in submerged culture in shake flasks on a medium
      containing peptone, yeast extract and glucose. In pre-cultures, inoculated from
      an agar-grown culture, morphological and metabolic events were linked: the
      pellets originally produced protuberances when glucose was present in the medium,
      although glucose was not consumed. The protuberances were then liberated into the
      medium as second-generation pellets, at which time glucose consumption began and
      the rate of exopolysaccharide (EPS) production increased. The synchrony between
      events was repeated in cultures fed with either glucose or peptone and yeast
      extract. In main cultures, inoculated from a 16-day-old pre-culture, the biomass
      concentration increased linearly, while glucose consumption and EPS production
      were initially slow but then accelerated. Protuberances were produced and
      liberated similarly to the pre-culture, but there was less synchrony amongst the
      pellets. When glucose was added to such a culture on day 10, an EPS concentration
      of 5.7 g L(-1) was achieved on day 13, this being the highest reliable EPS
      concentration yet reported for submerged culture of G. lucidum. We conclude that
      a greater understanding of the morphological and physiological events during the
      culture of G. lucidum will allow the proposal of culture strategies to improve
      EPS production.

PMID- 15464610
TI  - Expression and trafficking of fluorescent viral membrane proteins in baculovirus
      transduced BHK cells.
AB  - Baculovirus vectors show promise as a novel tool for gene delivery into mammalian
      cells and gene transfer with wild-type baculovirus has been demonstrated both in
      vitro and in vivo. To study expression and intracellular trafficking of foreign
      viral membrane proteins in baculovirus-transduced mammalian cells, the envelope
      proteins, E1 and E2, of rubella virus (RV) were chosen as a model. The enhanced
      green fluorescent protein (EGFP) and a red fluorescent protein (RFP) were fused
      to the C-terminus of E1 and E2, respectively. The proteins were cloned under a
      cytomegalovirus (CMV) promoter and expressed as fluorescent fusion proteins in
      baculovirus-transduced baby hamster kidney (BHK) cells. Expression of the
      chimeric proteins in these cells showed that E1 was retained within the ER and
      cis-Golgi when expressed alone. In contrast, E2 was efficiently transported to
      the trans-Golgi network (TGN). However, when expressed together, E1 co-localized
      with E2 in TGN and to some extent in the lysosomes. The recombinant baculovirus
      vectors were able to transduce the BHK cells efficiently and the fluorescent
      fusion constructs allowed easy detection of the trafficking events in the
      transduced mammalian cells. Consequently, this technique should have wide
      applications when intracellular analysis of protein synthesis and maturation is
      under study.

PMID- 15464611
TI  - Modelling of glucoamylase thermal inactivation in the presence of starch by
      artificial neural network.
AB  - Thermal inactivation is suspected to be a limiting factor for use of glucoamylase
      in starch saccharification at elevated temperatures. Thus, inactivation of the
      enzyme has been studied in the presence of reagents (enzyme, substrate and
      product in wide range of concentrations, and moderate stirring). The influence of
      substrate and glucose as stability modulators showed the complexity of the
      studied system. Hence, one might expect multilateral correlations that could
      depreciate some efforts for phenomenological modelling. These obstacles forced to
      apply artificial neural network (ANN) modelling to map the enzyme activity
      decays. For this purpose, a dynamic network with four hidden neurons was
      selected. The database containing 42 data vectors was used for neural model
      training and verification process. The standard error of calculations and
      correlation coefficient (0.997-0.999) for dynamic simulations has proved
      correctness of the developed ANN.

PMID- 15464612
TI  - Kinetic study of detoxification of dilute-acid hydrolyzates by Ca(OH)2.
AB  - Detoxification of dilute-acid hydrolyzates by addition of Ca(OH)(2) (overliming)
      and cultivation of the detoxified hydrolyzates by Saccharomyces cerevisiae were
      examined. The examined overliming involves increasing the pH of the hydrolyzates
      to 9, 10, 11 or 12, keeping up to 90 min at different temperatures of 30, 45 and
      60 degrees C, followed by readjustment of the pH to 5. Increasing the pH, time
      and/or temperature resulted in more effective degradation of furans and resulted
      in better fermentability for both of the tested hydrolyzates, but higher loss of
      the sugars was observed as well. Overliming of glucose and furfural solution at
      pH 12 showed a rapid decrease in concentration of these chemicals followed by a
      slow degradation process. Therefore, a kinetic model was proposed for the
      detoxification, where the sugars or furans make transient complexes with calcium
      ions and this complex will then be converted to the degradation product. The
      ANOVA analysis of the model resulted in an average R(2) of 0.99 for the model
      fitted to all the experimental data points.

PMID- 15464613
TI  - On-line cell mass monitoring of Saccharomyces cerevisiae cultivations by multi
      wavelength fluorescence.
AB  - The catalyst in bioprocesses, i.e. the cell mass, is one of the most challenging
      and important variables to monitor in bioprocesses. In the present study, cell
      mass in cultivations with Saccharomyces cerevisiae was monitored on-line with a
      non-invasive in situ placed sensor measuring multi-wavelength culture
      fluorescence. The excitation wavelength ranged from 270 to 550 nm with 20 nm
      steps and the emission wavelength range was from 310 to 590 nm also with 20 nm
      steps. The obtained spectra were analysed chemometrically with the multi-way
      technique, parallel factor analysis (PARAFAC), resulting in a decomposition of
      the multivariate fluorescent landscape, whereby underlying spectra of the
      individual intrinsic fluorophors present in the cell mass were estimated.
      Furthermore, gravimetrically determined cell mass concentration was used together
      with the fluorescence spectra for calibration and validation of multivariate
      partial least squares (PLS) regression models. Both two- and three-way models
      were calculated, the models behaved similarly giving root mean square error of
      prediction (RMSEPs) of 0.20 and 0.19 g l(-1), respectively, when test set
      validation was used. Based on this work, it is evident that on-line monitoring of
      culture fluorescence can be used for estimation of the cell mass concentration
      during cultivations.

PMID- 15464614
TI  - Synthesis of levan in water-miscible organic solvents.
AB  - The synthesis of levan using a levansucrase from a strain of Bacillus subtilis
      was studied in the presence of the water-miscible solvents: acetone, acetonitrile
      and 2-methyl-2-propanol (2M2P). It was found that while the enzyme activity is
      only slightly affected by acetone and acetonitrile, 2M2P has an activating effect
      increasing the total activity 35% in 40-50% (v/v) 2M2P solutions at 30 degrees C.
      The enzyme is highly stable in water at 30 degrees C; however, incubation in the
      presence of 15 and 50% (v/v) 2M2P reduced the half-life time to 23.6 and 1.8
      days, respectively. This effect is reversed in 83% 2M2P, where a half-life time
      of 11.8 days is observed. The presence of 2M2P in the system increases the
      transfer/hydrolysis ratio of levansucrase. As the reaction proceeds with 10%
      (w/v) sucrose in 50/50 water/2M2P sucrose is converted to levan and an aqueous
      two-phase system (2M2P/Levan) is formed and more sucrose can be added in a fed
      batch mode. It is shown that high molecular weight levan is obtained as an
      hydrogel and may be easily recovered from the reaction medium. However, when high
      initial sucrose concentrations (40% (w/v) in 50/50 water/2M2P) are used, an
      aqueous two-phase system (2M2P/sucrose) is induce, where the synthesized levan
      has a similar molecular weight distribution as in water and remains in solution.

PMID- 15464615
TI  - Synthesis by microwave irradiation of a substituted benzoxazine parallel library
      with preferential relaxant activity for guinea pig trachealis.
AB  - An efficient, facile, and practical parallel combinatorial synthesis of
      substituted-benzoxazines under microwave irradiation was described. The procedure
      involved the use of a microwave oven especially designed for organic synthesis
      suitable for parallel synthesis of solution libraries. A demonstration 19
      membered library of substituted N,N-dimethyl- and N-methyl-benzoxazine amide
      derivatives, structurally related to the potassium channel opener cromakalim, was
      generated by both conventional and microwave procedures, achieving a reduction
      from 7 h to 30-36 min in library generation time for the microwave approach. All
      the synthesized compounds were tested using the in vitro models of rat aorta and
      guinea pig trachea rings pre-contracted with phenylephrine and carbachol,
      respectively. All N,N-dimethyl amide derivatives showed a relaxant activity
      higher on guinea pig trachea rings than on rat aorta rings.

PMID- 15464616
TI  - Esters, amides and substituted derivatives of cinnamic acid: synthesis,
      antimicrobial activity and QSAR investigations.
AB  - A series of esters (I(a-k)), substituted derivatives (II(a-d)) and amides (III(a
      q)) of cinnamic acid were synthesized and evaluated as antibacterial and
      antifungal agents. All the derivatives belonging to the series I, II and III
      showed antimicrobial activity comparable to the standard. Compounds I(f) and
      II(c) proved to be the most effective compounds. Quantitative structure-activity
      relationship (QSAR) investigation with multiple linear regression analysis was
      applied to find a correlation between different calculated physicochemical
      parameters of the compounds and biological activity. The quantitative models
      relating the structural features of cinnamic acid derivatives I(a-k), II(a-d) and
      III(a-q) and their antimicrobial activity showed that Gram negative Escherichia
      coli and Candida albicans (fungus) were the most sensitive microorganisms.

PMID- 15464617
TI  - Investigation of structure-activity relationships in a series of glibenclamide
      analogues.
AB  - In this study, the synthesis of 15 new glibenclamide analogues is described. The
      conformational trends of these analogues were investigated using Monte Carlo
      conformational analysis. The conformational analysis results resolved the
      discrepancy between previous molecular modelling simulations of glibenclamide and
      allowed rationalizing the effect of aqueous environment on the overall
      conformation. The 3D-QSAR study was carried out with respect to the compounds'
      ability to antagonize the [(3)H]-glibenclamide binging in rat cerebral cortex.
      Superimposition of the antagonists was performed using the conformations derived
      from atom-by-atom fit to the glibenclamide crystal structure and this alignment
      was used to develop CoMFA models. CoMFA provided a good predictability: number of
      PLS components = 2, q(2) = 0.876, R(2) = 0.921, SEE = 0.455 and F = 70. Best
      CoMFA models showed the steric and lipophilic properties as the major interacting
      forces whilst the electrostatic property contribution was a minor factor.

PMID- 15464618
TI  - Synthesis and anti-tuberculosis activity of N-aryl-C-nitroazoles.
AB  - Twelve N-aryl derivatives of 4-nitroimidazole, 2-methyl-4-nitroimidazole, 4
      nitropyrazole or 3-nitro-1,2,4-triazole have been synthesized either by a
      degenerated ring transformation reaction of 1,4-dinitroimidazoles with 4
      substituted anilines or by a condensation of fluoronitrobenzenes with salts
      prepared from C-nitro-1H-azoles and 1,8-diazabicyclo[5.4.0]-7-undecene. The
      Tuberculosis Antimicrobial Acquisition and Coordinating Facility has provided
      anti-mycobacterial data concerning inhibition activity of 12 compounds.

PMID- 15464619
TI  - Synthesis of 2-amino-3-heteroaroylthiophenes and evaluation of their activity as
      potential allosteric enhancers at the human A1 receptor.
AB  - 2-Amino-3-benzoylthiophenes are allosteric enhancers of agonist binding to the
      adenosine A(1) receptor. New compounds bearing an heteroaroyl instead of the
      benzoyl moiety at the 3-position of the thiophene were synthesized. The phenyl
      ring was replaced with heterocycles that possess heteroatoms able to form
      hydrogen bonds (2-furanyl, 2-benzofuranyl, 2-pyridinyl in compounds 2-13) or with
      a thienyl moiety as isoster of the phenyl ring (2-thienyl, 3-thienyl and 5-halo-2
      thienyl in compounds 14-29). The effect of several alkyl substituents at
      positions 4 and 5 of the thiophene ring to increase enhancer activity was
      determined. The ability of the new molecules to reduce the cAMP content in CHO
      cells expressing the human adenosine A(1) receptor was evaluated. Compounds 2-13
      with hydrogen bond-forming heteroatoms did not show significant activity as
      allosteric enhancers. On the other hand, compounds 15-16 and 19-20 with an
      unsubstituted thienyl moiety as replacement for the phenyl ring were nearly as
      efficacious as PD 81,723, the prototypical A(1) allosteric enhancer. Alkyl
      substituents at positions 4 and 5 of the thiophene ring were tolerated while a
      substituted piperidine ring was not tolerated. We conclude that hydrogen bonds
      could not be formed in the domain of the receptor that accommodates the phenyl
      ring of 2-amino-3-benzoylthiophene derivatives, indicating that this domain is
      hydrophobic.

PMID- 15464620
TI  - Synthesis of some new 5-(2-substituted-1,3-thiazol-5-yl)-2-hydroxy benzamides and
      their 2-alkoxy derivatives as possible antifungal agents.
AB  - The 2-hydroxy-5-(1,3-thiazol-5-yl) benzamide (4a), 5-(2-amino-1, 3-thiazol-5-yl)
      2-hydroxy benzamide (4b), 2-hydroxy-5-(2-alkyl-1,3-Thiazol-5-yl) benzamide (4c
      and 4d), 5-(2-[(N-substituted aryl)amino]-1,3-thiazol-5-yl)2-hydroxy benzamides
      (6a-j) were prepared by reacting 5-(bromoacetyl) salicylamide (2) with thiourea,
      thioformamide, thioalkylamide (3c-d) and substituted thioureas (5a-j) in absolute
      ethanol. These compounds were converted to 5-(2-substituted-1,3-thiazol-5-yl)-2
      alkoxybenzamides and 5-(2-N-(substituted aryl)-1,3-thiazol-5-yl)-2-alkoxy
      benzamides (8a-g) by reacting with n-alkylbromides (7a-b) in presence of a base.
      The newly synthesized compounds were characterized by IR, (1)H-NMR and mass
      spectral data. Compounds were also screened for their antifungal activity.

PMID- 15464621
TI  - Synthesis and biological activity of new derivatives of 3-(3,4-diaryl-1,2,4
      triazole-5-yl)propenoic acid.
AB  - New 3-(3,4-diaryl-1,2,4-triazole-5-yl)propenoic acid derivatives (8-14) were
      synthesized by condensation of N(3)-substituted amidrazones (1-7) with maleic
      anhydride. Molecular structure of obtained compounds was confirmed by an
      elemental analysis, IR and (1)H NMR spectra, and the X-ray crystallography for
      compound 11. The influence of the compound 9 on the central nervous system (CNS)
      of mice in some behavioural test was examined. The investigated compound showed
      anticonvulsive activity and potent antinociceptive action.

PMID- 15464622
TI  - 8-Substituted-9-deazaxanthines as adenosine receptor ligands: design, synthesis
      and structure-affinity relationships at A2B.
AB  - A number of 8-substituted-9-deazaxanthine derivatives (1,3-dialkyl-6-substituted
      1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-diones) were prepared and tested for their
      antagonistic activity at the recombinant human adenosine receptors, in particular
      at the A(2B) and A(2A) receptor subtypes. Compounds endowed with micromolar to
      nanomolar binding affinities, but with poor A(2B)/A(2A) selectivity, were
      obtained. Preliminary quantitative structure-affinity relationships suggested
      that the binding potency at the A(2B) receptor is mainly modulated by the
      electronic and lipophilic properties of the ligands.

PMID- 15464623
TI  - Synthesis and GABA uptake inhibitory properties of 6-aryl iminoxymethyl
      substituted nipecotic acids.
AB  - Nipecotic acid derivatives bearing an aryl iminoxymethyl side chain at the
      position 6 were synthesised and tested for their GABA uptake inhibitory
      properties. Contrarily to the N-substituted derivatives 2, 3 the introduction of
      the oxime function in the side chain of analogues of the active nipecotic
      derivative 4 does neither increase, nor maintain the activity.

PMID- 15464624
TI  - Editorial.

PMID- 15464625
TI  - Regionally contaminated aquifers--toxicological relevance and remediation options
      (Bitterfeld case study).
AB  - Large-scale contaminated megasites like Bitterfeld in eastern Germany are
      characterized by a regional contamination of soil, surface water and groundwater
      as a result of a long and varied history of chemical production. While the
      contaminants in soils and sediments mostly represent a localized problem,
      pollutants in groundwater may spread to uncontaminated areas and endanger
      receptors like surface water and drinking water wells according to the site
      specific hydrologic regime. From the toxicological point of view, the
      contaminants at the Bitterfeld megasite represent a dangerous cocktail of various
      harmful substances coming from a multitude of sources. Appropriate remediation
      techniques must be able to remedy the specific problems arising from hot spot
      areas within the megasite in addition to preventing a further extension of the
      contaminated zone towards uncontaminated compartments. Therefore, a combination
      of specifically designed remediation technologies based on the pump and treat
      principle with in situ technologies, such as reactive walls and
      monitored/enhanced natural attenuation, is necessary to efficiently address the
      miscellaneous challenges at this megasite. In this paper, the currently known
      contaminant distribution, the associated problems for human health and the
      environment and possible remediation strategies are presented for the Bitterfeld
      megasite.

PMID- 15464626
TI  - Ecotoxicological and environmental problems associated with the former chemical
      plant in Tarnowskie Gory, Poland.
AB  - The environmental problems related to the former chemical plant in Tarnowskie
      Gory, with respect to the Quaternary and Triassic groundwater as main receptors,
      are described and the eco-toxicological impact is discussed. The historical use
      of that site included industrial mining of ores (Ag, Pb, Zn) and use of Ba, B,
      Sr, Al, Cu during production of pigment. The majority of used and produced
      substances were toxic or hazardous. The applied technologies resulted in
      generation of waste which were mostly dumped without any elementary protection
      principles. Hydrodynamic modelling showed potential hazard to water-intakes. The
      variations of spatial distributions of selected contaminants within the Triassic
      carbonate series indicate that the chemical waste dumped in vicinity of the plant
      are the sources of groundwater contamination of boron. The results of soil and
      groundwater monitoring at the constructed landfill show significant
      contamination, mainly due to leaching from dumped waste, but also from
      infiltration of non-operating underground installations, and spills of toxic
      substances during the plant operation. The Quaternary aquifers are heavily
      contaminated due to the leaching out of chemical compounds from dumping sites.
      This is hazardous to the Triassic reservoirs--the main sources of potable water
      for the region. The characteristics of the key contaminants (As, B, Ba and Sr)
      are provided, including their transport, fate and toxicity. The spatial and
      temporal distribution of contaminants in groundwater is presented, and observed
      trends of groundwater quality decrease, mainly with respect to the Triassic
      aquifers, are discussed. The groundwater risk assessment being developed for the
      Tarnowskie Gory site should consider the present situation, and provide an
      approach towards evaluation and assessment of the required remediation measures.

PMID- 15464627
TI  - Transport behaviour and natural attenuation of organic contaminants at spill
      sites.
AB  - Organic contaminants pose a significant threat to groundwater resources. These
      contaminants are often released as non-aqueous phase liquids (NAPLs) during
      spills of, for example, gasoline, crude oil, creosote, coal tar or chlorinated
      solvents. Once released, the liquids seep downward and dissolve into the
      groundwater. In many cases, the impacted groundwater contains a mixture of
      contaminants, either due to the complexity of the NAPL (e.g., gasoline) or due to
      co-disposal/co-spillage (e.g., landfill leachates). Many organic contaminants are
      hazardous to human health and the environment and therefore threaten our potable
      water resources and natural ecosystems. Active remediation of contaminated
      groundwater is often very expensive so that cost-effective alternatives have to
      be found. If natural attenuation is intended to be used as a means of achieving
      specific remedial objectives at a contaminated site, it will require a sound
      understanding of the ongoing processes as well as careful control and monitoring
      ("monitored natural attenuation" (MNA)). Therefore, a major goal of remediation
      research today is to develop methods to predict the mass fate of multiple organic
      compounds in heterogeneous aquifers under natural conditions.

PMID- 15464628
TI  - Risk potentials for humans of original and remediated PAH-contaminated soils:
      application of biomarkers of effect.
AB  - Contaminated soils represent a potential health risk for the human population.
      Risk assessment for humans requires specific methods, which must reflect the
      peculiarities of human behaviour, physiology and biochemistry with respect to
      contaminant uptake and processing. Biomarkers of effect or exposure have become
      an appropriate tool. Organic pollutants influence the expression profile of
      cytochromes P450 (CYP), and CYP1A1 has been shown to be a suitable biomarker for
      polycyclic aromatic hydrocarbons (PAH). The latter are widely distributed in
      soils and constitute an important soil contamination. Upon intake of PAH
      contaminated soils, CYP1A1 is induced in various organs of rats and minipigs.
      Increased CYP1A1-levels in lung, kidney and spleen, after oral soil intake,
      indicate that contaminants escape the primary duodenal and hepatic metabolism and
      reach further organs. Dose-response relationships reveal that induction effects
      are to be expected in children based on known exposure conditions. Generally,
      CYP1A1-induction does not correlate with results of toxicity tests with lower
      organisms, performed with the same soils. The organic carbon content is largely
      responsible for this discrepancy. It severely affects the toxicity of soil bound
      PAH for microorganisms, but obviously affects the mobilization efficiency for PAH
      in the gastro-intestinal tract of mammals to a minor extent. Soil remediation by
      different methods may result in a significant reduction of the PAH content and of
      toxicity. Ingestion of remediated soils by rats shows, however, that the
      induction potential for CYP1A1 is only slightly decreased after remediation. This
      means that the major inducing components resist biological remediation or soil
      washing and remain in the soil. Because data obtained with experimental animals
      form the guiding principle for in vitro tests to be developed, the suitability of
      the animal model used for extrapolations to humans has to be proven. Upon soil
      ingestion, minipigs show a tissue-specific response pattern, which substantially
      differs from that of rats, which are widely used as animal models. It is not
      known which response pattern resembles that of man. In summary, cytochromes P450,
      in particular CYP1A1, are suitable biomarkers to assess the bioavailability of
      soil bound contaminants and their effects on mammalian species. There are,
      however, a number of questions to be answered in order to develop an in vitro
      test for human risk assessment. This concerns, for example, the identification of
      the suitable animal model, the identification of biomarkers for other
      contaminants and concepts to transpose the in vivo data to in vitro technologies
      or to mathematical modelling.

PMID- 15464629
TI  - Hazard identification for contaminants.
AB  - In recent years, the recognition of generation of large quantities of toxicants
      and their by-products due to the industrial and/or cultural activities and
      transport and their persistence in the environment and biological activities
      brings out the necessity and importance of their assessment of risk they pose to
      the ecosystems (e.g. aquatic environment-coastal waters, rivers, lakes and ground
      water). Indeed, understanding the impacts of contaminants on the environment,
      including the organisms which live in it, is rather complicated. Nevertheless,
      the need for protection of the scarce natural resources in the environment and
      wiser use of them brings the necessity and importance of focusing more attention
      to the issue. Accordingly the process of ecological risk assessment (ERA) has
      evolved rapidly since the Environmental Protection Agency (EPA) issued a
      framework for ecological risk assessment in 1992. The ecological risk assessment
      involves three stages in a continuous process: (1) problem formulation (problem
      identification-hazard identification), (2) the analysis of exposure and effects
      and (3) risk characterisation. Risk management follows the risk characterisation.
      Of these stages, problem identification is the most critical one which
      establishes the direction and scope of the ecological risk assessment. The stage
      involves identifying the actual environmental value(s) to be protected
      (assessment endpoints) and selecting ways in which these can be measured and
      evaluated (measurement endpoints). The accuracy of the risk estimation is largely
      based on the availability of the key information about the contaminant
      characteristics, ecosystem at risk and ecological effects and the less
      uncertainty associated with them. The key information required during this phase
      of the risk assessment process are as follows: (a) potential/actual contaminant
      of concern, (b) source of contaminant; current and historic use, (c) mode of
      action of the contaminant, (d) contaminant characteristics (e.g.
      physical/chemical properties and environmental behaviour, persistence in the
      ecosystem, transformation products and bioaccumulation), (e) ecosystem
      potentially at risk and (f) areas of uncertainty. Finally based on these
      information a conceptual model has to be developed to define the possible
      exposure and assessment scenarios. Herein, the aforementioned key issues
      concerning the problem-hazard identification stage of ecological risk assessment
      for contaminants have been briefly reviewed.

PMID- 15464630
TI  - Enhancement of the biodegradability of aromatic groundwater contaminants.
AB  - Groundwater (GW) from the Bitterfeld industrial region, Central Germany, is
      contaminated mainly with monochlorobenzene (MCB). Accordingly, current research
      addresses the development of feasible in situ groundwater remediation
      technologies. Although easily degradable under aerobic conditions, MCB persists
      in the essentially anaerobic Bitterfeld aquifer. Therefore, we focused on primary
      oxidation of MCB and the subsequent anaerobic biodegradability of MCB oxidation
      products by the indigenous microbial community. In groundwater microcosms, most
      efficient MCB removal was observed upon treatment with Fenton's reagent (H2O2 +
      Fe2+), which produces the highly reactive hydroxyl radical and Fe3+
      simultaneously. Phospholipid fatty acid analysis following different treatments
      suggested respective shifts of the microbial community compositions, and
      indicated that Fenton's reagent had a rather beneficial than an adverse effect on
      biomass development. Potential metabolites of hydroxyl radical attack on MCB such
      as chlorohydroquinone, hydroquinone, catechol, resorcinol, and phenol were
      anaerobically degraded by the groundwater microbial community under Fe3+ 
      reducing conditions.

PMID- 15464631
TI  - Applying whole water samples to cell bioassays for detecting dioxin-like
      compounds at contaminated sites.
AB  - Methodology was developed in order to rapidly and cost-efficiently screen whole
      water samples without extraction for the presence of dioxin-like compounds using
      a cell bioassay approach. Presence of dioxin-like compounds was indicated by the
      induction in the rainbow trout (Oncorhynchus mykiss) liver cell line, RTL-W1, of
      cytochrome CYP1A, which was measured as 7-ethoxyresorufin-O-deethylase (EROD)
      activity. Two simple culture media, L-15/ex and Earle's-G, prepared in tissue
      culture water and supplemented with 5% serum, proved suitable for supporting RTL
      W1 cell viability and induction of EROD activity by the model inducers, 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and benzo[a]pyrene (BaP). Preparation of the
      same simplified media using whole surface and ground water instead of tissue
      culture water again allowed EROD induction by spiked TCDD and BaP to be detected
      but higher concentrations of inducers were necessary. Despite this reduced
      sensitivity, RTL-W1 cells responded to 4 out of 40 ground water samples from a
      former oil and lignite processing site with significant EROD induction. In the
      future, the value of the bioassay is as an inexpensive means of quickly screening
      ground and surface water samples to identify high contaminant levels particularly
      at industrial sites, where detailed site-investigations and long-term monitoring
      programs are required.

PMID- 15464632
TI  - Ecotoxicological effects at contaminated sites.
AB  - Contamination sites pose significant environmental hazards for terrestrial and
      aquatic ecosystems. They are important sources of pollution and may result in
      ecotoxicological effects on terrestrial, groundwater and aquatic ecosystems. At
      severely contaminated sites, acute effects occur, but the core problem lies in
      long-term chronic effects. Ecotoxicological effects occur at all levels of
      biological organization, from the molecular to the ecosystem level. Not only
      certain organisms may be affected, but the ecosystems as a whole, both
      terrestrial and aquatic, in its function and structure. Contaminants at large
      contaminated sites often share critical properties such as high acute and/or
      chronic toxicity, high environmental persistence, often high mobility leading to
      contamination of groundwater, and high lipophilicity leading to bioaccumulation
      in food webs. Contaminants present at polluted sites occur as mixtures, therefore
      interactions between individual compounds are of importance. The bioavailability
      is a key factor for ecotoxicological effects of contaminants. This is
      demonstrated by a case study on organotins. Organotins belong to the most toxic
      pollutants known so far for aquatic life. Widespread contamination of harbor
      sediments occurs globally due to the ongoing use of organotins in antifouling
      paints in large ships. In lake sediments, tributyl- and triphenyltin are very
      persistent and bioavailable to biota even after a long time. Bioavailability of
      these compounds is dependent on pH and organic matter. Organotins are accumulated
      in sediments, but remobilization occurs when contaminated sediments are disturbed
      and dredged. A key question in dealing with contaminated sites is the assessment
      and evaluation of the toxicity of contaminants to the environment. Usually,
      established OECD tests and whole effluent toxicity tests are performed for an
      ecotoxicological evaluation and for hazard assessment. However, these assays are
      often expensive, laborious and sometimes not sensitive enough. As a consequence,
      we have used fast and reliable in vitro systems such as fish cell lines for the
      evaluation of sediments and landfill leachates contaminated by polychlorinated
      hydrocarbons (PAH). Determination of cytotoxicity as a measure for acute
      toxicity, and induction of cytochrome P4501A (CYP1A) as a biomarker of exposure
      and toxicity were found to be important measures, which can be used for hazard
      and risk assessment. We have developed a concept for the ecotoxicological
      evaluation of PAH contamination based on induction equivalents, which can be
      applied for aquatic and terrestrial ecosystems. One of the key question and
      present gaps, however, includes the long-term chronic ecotoxicological effects on
      soil and aquatic biota, which are largely unknown.

PMID- 15464633
TI  - Economic valuation through cost-benefit analysis--possibilities and limitations.
AB  - The economic approach used to evaluate effects on human health and the
      environment centres around cost-benefit analysis (CBA). Thus, for most
      economists, economic valuation and CBA are one and the same. However, the
      question of the possibilities and limitations of cost-benefit analysis is one of
      the most controversial aspects of environmental research. In this paper, the
      possibilities and limitations of CBA are analysed. This is done not only by
      explaining the central elements of CBA, but also by commenting on criticism of
      it. What becomes clear is that CBA is not only a mere mechanism of
      monetarisation, but a heuristic model for the whole process of valuation. It can
      serve as a guideline for collecting the necessary data in a systematic way. The
      limits of CBA can be mainly seen in the non-substitutability of essential goods,
      irreversibility, long-term effects and inter-generational fairness.

PMID- 15464634
TI  - Epilepsy surgery for tuberous sclerosis.
AB  - Tuberous sclerosis complex is often associated with medically refractory epilepsy
      secondary to cortical tubers. Previous studies have identified an association
      between early seizure onset, greater seizure burden, and mental retardation in
      childhood. Early effective seizure control could therefore significantly reduce
      the adverse developmental effects of chronic epilepsy in tuberous sclerosis
      complex. In medically intractable epileptic patients, surgical treatment has been
      demonstrated to reduce or abolish seizures and the associated burden for the
      child and its environment. Epilepsy surgery has not been widely used in patients
      with tuberous sclerosis complex thus far, mostly because of the concern that the
      multifocal nature of the cortical lesions could be associated with the
      development of independent epileptogenic zones. Advances in
      electroencephalographic techniques, functional neuroimaging, and invasive
      cortical mapping are changing this view and allowing an increased number of
      tuberous sclerosis complex patients to be evaluated for resective surgery.
      Additional techniques emerging in the neurosurgical field may add further
      treatment options to the current state of the art.

PMID- 15464635
TI  - Age and antiepileptic drugs influence topiramate plasma levels in children.
AB  - The influence of age and comedication on the dose-to-level ratio of topiramate
      was examined in 91 children with epilepsy treated with topiramate. The topiramate
      dosing and plasma concentrations, as well as those of their concomitant
      antiepileptic drugs were examined retrospectively. The dose-to-level ratio was
      used as a measure of clearance and was calculated as the weight-normalized
      topiramate dose (mg/kg/day) divided by the steady-state trough plasma drug level
      in the child. The children were classified in age groups and treatment groups;
      topiramate was administered with an enzyme inducer (n = 32), with a nonenzyme
      inducer (n = 49), or as monotherapy (n = 10). The topiramate clearance in
      children aged 0-8 years compared with those aged 9-17 years was more than twofold
      higher if treated with an enzyme-inducing antiepileptic drug and 1.5-fold higher
      if treated with a nonenzyme inducer. Children receiving enzyme inducers had a
      more than twofold higher clearance compared with those who did not. Within all
      age groups, significant differences in topiramate clearance were observed between
      those receiving enzyme inducers and those receiving nonenzyme inducers or
      monotherapy. Thus younger age and concomitant enzyme inducers, both acting
      independently, significantly increased the clearance of topiramate in children.
      This effect has to be considered to optimize treatment in the individual patient.

PMID- 15464636
TI  - A new model of stroke and ischemic seizures in the immature mouse.
AB  - Ischemic brain injury from stroke is an important cause of disability in infants
      and children, but current experimental models for the disorder are complex. These
      preparations require occlusion of small intracerebral vessels or common carotid
      artery ligation combined with exposure to reduced levels of oxygen. Unilateral
      carotid artery ligation alone was sufficient to cause brain injury in more than
      70% of 12-day-old CD1 mice. Using a blinded behavioral rating scale of seizure
      activity in mice, a direct, highly significant correlation between the severity
      of seizures over the 4-hour period after ligation and the severity of histologic
      brain injury 7 days later (Spearman's rho = 0.835, P < 0.001) was documented.
      This study presents the first model of stroke in immature mice produced by
      unilateral carotid artery ligation alone, and the first to demonstrate a clear
      correlation between acute ischemia-induced seizures and brain injury. This new
      model should be useful for examining the pathogenesis of stroke in the immature
      brain and the potential contribution of seizures to final outcome.

PMID- 15464637
TI  - Lymphocyte subsets in Bell's palsy: immune pathogenesis and outcome prediction.
AB  - The aim of this prospective study is to define the prognostic significance of
      lymphocyte subset analysis in children with Bell's palsy. Lymphocyte subgroup
      analysis in peripheral blood was performed in 17 children with Bell's palsy by
      using flow cytometry. Before a standard protocol of corticosteroid treatment,
      patients were categorized into two groups for facial nerve impairment on the
      basis of the clinical findings: Group 1 (mild to moderate impairment), 7
      patients; and Group 2 (severe impairment), 10 patients. Outcome of the patients
      was evaluated at the end of 3 months follow-up and categorized as satisfactory
      recovery (n = 12) or unsatisfactory recovery (n = 5). Decreased percentages of B
      cells (CD19) and T helper/inducer (CD4) subsets were measured in patients with
      Bell's palsy compared with age-matched healthy control patients. Patients with
      severe impairment had significantly lower percentages of CD4 and CD19 subsets,
      whereas patients with mild to moderate impairment had only decreased percentage
      of CD19 subsets. There was no statistically significant difference in the
      percentage of lymphocyte subsets between the patients with satisfactory and
      unsatisfactory recovery. These results provide additional support for cell
      mediated immunopathogenesis in patients with Bell's palsy, without any prognostic
      significance for the outcome.

PMID- 15464638
TI  - The clinical and surgical aspects of spinal tumors in children.
AB  - A series of 20 pediatric patients underwent surgery for spinal tumor at the
      Department of Neurosurgery, Gulhane Military Medical Academy between 1995 and
      2003. Motor weakness and reflex changes were the main initial signs in these
      patients. Epidural tumors and intradural-extramedullary tumors were in equal
      number, and total tumor removal was achieved in most of the patients without
      adjuvant treatment. Laminotomy was the main surgical method in 60% of the
      patients with spinal tumor, especially in children younger than 3 years of age.

PMID- 15464639
TI  - Hypoxic-ischemic encephalopathy: correlation of serial MRI and outcome.
AB  - Twenty-four patients with hypoxic-ischemic encephalopathy were examined with
      serial magnetic resonance imaging up to 4 years of age. Magnetic resonance
      imaging studies were performed in the neonatal period, at the fourth month and
      the fourth year of age, and the findings were compared with the patients'
      neurodevelopmental outcome at the fourth year of age. Periventricular signal
      alterations and deep gray matter involvement were usually evident in the initial
      magnetic resonance imaging studies, and encephalomalacia, periventricular
      leukomalacia, and atrophy were the common findings on follow-up magnetic
      resonance imaging studies. In the patients with hypoxic-ischemic encephalopathy,
      some correlation between magnetic resonance imaging findings and
      neurodevelopmental outcome was recognized. The patients with deep gray matter
      involvement on the initial magnetic resonance imaging had a poor prognosis, and
      the ones with normal magnetic resonance imaging findings had a favorable
      neurodevelopmental outcome. On the follow-up magnetic resonance imaging findings,
      encephalomalacia and periventricular leukomalacia were associated with poor
      neurodevelopmental outcome. In predicting the neurologic outcome at 4 years of
      age, magnetic resonance imaging findings of the neonatal period had the highest
      negative predictive value, whereas magnetic resonance imaging findings at 4
      months of age and 4 years of age had the highest positive predictive value.

PMID- 15464640
TI  - Benign opsoclonus in preterm infants.
AB  - Opsoclonus is a rare childhood ocular motility disorder characterized by
      irregular, chaotic, involuntary bursts of high amplitude, back-and-forth
      oscillations of the eyes,without pause intervals. Although this disorder is
      associated with neuroblastoma and other neural crest tumors, as well as with
      other neurologic abnormalities, it was also reported in healthy infants. The
      purpose of this study was to prospectively investigate the prevalence of
      opsoclonus in preterm infants, and to find any conditions associated with this
      disorder. Between August 2000 and April 2003, 528 consecutive preterm infants
      with gestation of less than 33 weeks or birth weight of less than 1500 gm were
      examined in accordance with our medical centers' retinopathy of prematurity
      screening policy. Opsoclonus was identified in three patients (0.6%), who were
      all otherwise physically and neurologically intact. One patient developed
      threshold retinopathy of prematurity that resolved after laser treatment. On
      follow-up examinations, the opsoclonus gradually disappeared by the age of 6
      months in all infants,with no other complications. This study suggests that
      opsoclonus can be a benign, self-limiting phenomenon in preterm infants as was
      previously reported in term infants. However, because of the risk of severe
      associated illnesses, it is prudent to perform several diagnostic procedures and
      to continue careful follow-up until this phenomenon spontaneously resolves.

PMID- 15464641
TI  - Effect of carbamazepine and valproate on bone mineral density.
AB  - The objective of this study was to examine the effect of carbamazepine and
      valproate monotherapy on bone mineral density in children. Femoral neck area bone
      mineral density was measured by dual-energy x-ray absorptiometry in 31 healthy
      children and 33 children with idiopathic epilepsy treated with either
      carbamazepine (n = 17) or valproate (n = 16) for more than 6 months. There were
      no significant differences between the control and study patients in age, height,
      weight, and physical activity. No patient had dietary restrictions or neurologic
      impairment. Serum levels (as mean +/- S.D.) of valproate and carbamazepine were
      53.75 +/- 23.94 microg/mL and 6.26 +/- 2.00 microg/mL, respectively, and the
      duration of treatment for each drug was 24.38 +/- 10.58 months and 31.76 +/-
      16.33 months, respectively. Calcium intake in the diet was similar in both the
      control and study groups. In the valproate-treated group, 25% of the patients
      were hypocalcemic, 6% had elevated alkaline phosphatase levels, and 50% were
      hypophosphatemic. In the carbamazepine-treated group, 17.6% of the patients were
      hypocalcemic and 35.3% were hypophosphatemic. Children treated with valproate had
      31.9% reduction in bone mineral density at the femoral neck area (P < 0.05); the
      20% reduction in bone mineral density in this anatomic location in carbamazepine
      treated children was not significant. In conclusion, valproate monotherapy, but
      not carbamazepine therapy, significantly reduces femoral neck area bone mineral
      density in children with idiopathic epilepsy.

PMID- 15464642
TI  - Ictus emeticus (ictal vomiting).
AB  - Vomiting is rarely the main ictal manifestation of epilepsy, and it is likely
      associated with more than one type of epilepsy. Its possible mechanism involves
      the spread of abnormal electrical activity through descending insular or limbic
      circuits. This report describes a child with difficult-to-control ictal vomiting
      arising from a left temporal epileptic focus. Ictus emeticus is a specific
      epileptic presentation which can have a chronic, intractable nature requiring
      repetitive therapeutic trials with antiepileptic medications. In the patient
      described here, the disease posed a diagnostic dilemma in its early stages. The
      ictal electroencephalogram is crucial for the diagnosis.

PMID- 15464643
TI  - Malignant migrating partial seizures in infancy.
AB  - Malignant migrating partial seizures in infancy is a rare, age-specific epileptic
      encephalopathy. It is characterized by onset before age 6 months, virtually
      continuous multifocal seizures with ictal electrical encephalographic activity
      shifting from one hemisphere to the other, no identifiable immediate or remote
      causes, intractability to antiepileptic drugs, and developmental arrest. This
      report adds two patients to the 21 previously described in the literature. One
      infant, microcephalic at birth, developed at age 4 months clusters of nearly
      continuous multifocal seizures with secondary generalization, refractory to
      antiepileptic drugs. By age 4.5 years she was seizure-free but remains without
      any cognitive or motor function. Patient 2, born with a normal head
      circumference, began seizures at age 3 months, never became seizure-free, and
      died at age 18 months. Electroencephalograms of both children were
      characteristic, and the neuroimaging finding was one of progressive cortical and
      subcortical atrophy. It has been hypothesized that neurotransmitter dysfunction
      with persistent, pronounced excitatory or cytotoxic mechanisms may explain the
      continuous, erratic epileptic activity. Awareness of malignant migrating partial
      seizures in infancy and research focused on its pathophysiologic mechanisms may
      reveal innovative treatments of this devastating, age-specific disorder.

PMID- 15464644
TI  - Familial subacute sclerosing panencephalitis in two siblings.
AB  - Subacute sclerosing panencephalitis is a form of chronic persistent measles
      encephalitis in childhood which rarely manifests after wild virus infection. One
      previous case of familial subacute sclerosing panencephalitis in two siblings and
      a number of reports of subacute sclerosing panencephalitis in one member of
      monozygous twins have been reported in the literature. This report describes a
      second sibling set who both contracted subacute sclerosing panencephalitis after
      concurrent sporadic measles infection. Two nonimmunized brothers developed
      neuropsychological decline and progressive myoclonic and complex partial seizures
      after earlier measles infection. Stereotyped periodic 5- to 8-second complexes in
      the electroencephalogram suggested the diagnosis of subacute sclerosing
      panencephalitis, subsequently confirmed by intrathecal and serum measles-specific
      immunoglobulin G synthesis and the presence of rubeola nucleocapsid protein and
      ribonucleic acid in the biopsied brain. The viral genome has not been further
      subtyped in either patient at this point. Although a rare event, subacute
      sclerosing panencephalitis cases involving familial and singular monozygous twins
      may shed light on a variety of host susceptibility factors and specific viral
      genotype features predisposing to this disease.

PMID- 15464645
TI  - The use of ultrasound for the diagnosis of spinal hemorrhage in a newborn.
AB  - We present a case of an unusually large spinal epidural hematoma in an infant
      after a total breech extraction, which was diagnosed by high-resolution
      ultrasonography. The lesion appeared unusually large, homogeneous, and isoechoic
      to the spinal cord. This case demonstrates the ability of ultrasound to diagnose
      the nature of the lesion, its exact location and full extent. Magnetic resonance
      imaging was used in this case only as a secondary modality to demonstrate the
      hemorrhagic nature of the lesion.

PMID- 15464646
TI  - Misdiagnoses in children with dopa-responsive dystonia.
AB  - Dystonia is a state of continuous contraction of groups of agonist and antagonist
      muscles resulting in a sustained abnormal posture. Dopa-responsive dystonia was
      first described in 1976 by Segawa. Patients typically have diurnal variation of
      their symptoms with worsening at the end of the day and a dramatic response to
      low-dose L-dopa. This report presents five consecutive children with dopa
      responsive dystonia who were misdiagnosed initially as spastic diplegic cerebral
      palsy, intractable epilepsy, hereditary spastic paraplegia, or a
      neurodegenerative disorder. There were two males and three females aged 3-13
      years (mean 8.6 years). They were monitored for up to 2 years (mean 14.8 months).
      One had focal, one axial, one segmental, and two generalized dystonia. The
      dystonia was paroxysmal in two (tiptoe walking and opisthotonus), and all had a
      progressive course. All children responded dramatically to L-dopa (mean 200
      mg/day), including three who were wheelchair-bound for several years. The
      difficulties in early diagnosis, variability of clinical presentation, and
      dramatic response to L-dopa will be illustrated. To conclude, dopa-responsive
      dystonia should be considered in any child who presents with paroxysmal or
      progressive hypertonia of unknown etiology, because it responds so dramatically
      to L-dopa.

PMID- 15464647
TI  - Pediatric tick paralysis: discussion of two cases and literature review.
AB  - This report describes two cases of tick paralysis in children diagnosed within a
      3-month period (May-July 2002) in rural South Carolina. Differing presenting
      symptoms consisted of acute onset of ataxia in one patient and acute ascending
      paralysis in the other. Ticks were present on the scalp of both patients and were
      removed immediately. Both girls demonstrated improvement of signs and symptoms
      within hours and complete recovery within 24 hours of tick removal. The diagnosis
      of tick paralysis must be considered in any patient, particularly children, who
      present with either acute ataxia or acute ascending paralysis. As in any clinical
      encounter, careful history and thorough general and neurologic examinations must
      be performed to exclude the possibility of tick attachment.

PMID- 15464649
TI  - How to attract students to child neurology.

PMID- 15464651
TI  - CSF ferritin as a marker for bacterial meningitis.

PMID- 15464653
TI  - Hemochromatosis.
AB  - Hemochromatosis is a common genetic disease with a wide range of clinical
      expression: from no symptoms to cirrhosis of the liver. The discovery of the gene
      has led to a genetic blood test useful in the diagnosis of hemochromatosis.
      Treatment by phlebotomy is simple and efficient and can prevent the development
      of cirrhosis, leading to a normal life expectancy.

PMID- 15464654
TI  - Pathogenesis of hereditary hemochromatosis.
AB  - Hereditary hemochromatosis comprises several inherited disorders of iron
      homeostasis characterized by increased gastrointestinal iron absorpstion and
      resultant tissue iron deposition. The identification of HFE and other genes
      involved in iron metabolism has greatly expanded our understanding of hereditary
      hemochromatosis. Two major hypotheses have been proposed to explain the
      pathogenesis of HFE-related hereditary hemochromatosis: the hepcidin hypothesis
      and the duodenal crypt cell programming hypothesis.

PMID- 15464655
TI  - Iron, the HFE gene, and hepatitis C.
AB  - Intrahepatic iron overload is commonly seen in chronic hepatitis C infection.
      High levels of intrahepatic iron may lead to accelerated liver injury and
      development of fibrosis and cirrhosis. This is frequently seen in hereditary
      hemochromatosis, which in most of the cases is caused by homozygous mutations in
      the HFE gene. In patients suffering from chronic hepatitis C, the presence of
      heterozygous HFE mutations associates with higher hepatic iron scores and
      advanced stages of fibrosis. HFE mutations must therefore be considered as
      important comorbidity factors in chronic hepatitis C infection.

PMID- 15464656
TI  - Wilson disease: pathophysiology, diagnosis, treatment, and screening.
AB  - Wilson disease is an autosomal recessive condition of copper metabolism that was
      once considered fatal. The identification of the gene for Wilson disease has led
      to a better understanding of the molecular defect underlying this disorder and
      has impacted on disease diagnosis for some individuals. Medical therapy with
      chelating agents or zinc salts remains the mainstay of therapy for most patients,
      and liver transplant is lifesaving for those with advanced disease refractory to
      medical therapy or with fulminant hepatic failure. Future cell-based and genetic
      therapies may provide a cure for this disorder.

PMID- 15464657
TI  - Hepatic porphyrias: diagnosis and management.
AB  - Porphyrias are a group of metabolic disorders in which there are defects in the
      normal pathway for the biosynthesis of heme, the critical prosthetic group for
      numerous hemoproteins. The clinical manifestations of the porphyrias can be
      highly varied, and patients may present to general physicians and be referred to
      a wide variety of subspecialists because of these manifestations. However, two
      major clinical forms are represented by the so-called "acute" porphyrias, in
      which patients suffer recurrent bouts of pain, especially pain in the abdomen,
      and the "cutaneous" porphyrias, in which patients have painful skin lesions.
      Knowledge of the factors chiefly responsible for regulating the rate of synthesis
      of heme has helped to explain how drugs and other factors may cause porphyria.
      Knowledge of the physical and chemical properties of porphyrins also forms an
      important part of the foundation for understanding the clinical manifestations of
      these diseases. Thus, the porphyrias can best be understood after reviewing the
      chemical properties of porphyrins and heme and the control of their biosynthesis.

PMID- 15464658
TI  - Alpha-1-antitrypsin deficiency: diagnosis and treatment.
AB  - Alpha-1-antitrypsin (AT) deficiency was first described in the late 1960s in
      patients with severe pulmonary emphysema. The recognition of AT deficiency as a
      cause of emphysema then led to what is still the prevailing theory for the
      pathogenesis of emphysema, the protease-antiprotease theory. Soon it was found
      that AT deficiency accounted for a significant number of cases of neonatal liver
      disease that were previously categorized as idiopathic. We now know that AT
      deficiency is the most common genetic cause of neonatal liver disease and the
      most frequent diagnosis necessitating liver transplantation. It has also been
      shown to cause chronic liver disease, cryptogenic cirrhosis, and hepatocellular
      carcinoma in adults never previously known to have liver disease in infancy or
      childhood. Observations indicate that genetic traits unlinked to the AT gene or
      environmental factors predispose to or protect AT-deficient individuals from
      liver disease.

PMID- 15464659
TI  - Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a well-recognized form of chronic
      liver disease affecting both children and adults that has gained increased
      recognition. Recently NAFLD has been associated with insulin resistance and its
      incidence and prevalence is likely increasing, paralleling the rise in obesity
      and diabetes mellitus in the United States. The article includes current thoughts
      on the natural history and pathogenesis of NAFLD and describes current trends in
      the diagnosis and treatment of this condition.

PMID- 15464660
TI  - Hepatitis C and steatosis.
AB  - Steatosis is a common finding in patients with chronic hepatitis C (CHC) due to a
      combination of the direct steatogenic effect of hepatitis C virus (HCV) and the
      prevalence of metabolic risk factors in the HCV population. Steatosis is now
      established as a risk factor for disease progression in CHC and significantly
      impacts therapeutic response. Research efforts should continue to focus on
      defining the complex viral and host interactions involved in the pathogenesis of
      HCV-related steatosis so that future therapeutic strategies may be accurately and
      appropriately targeted.

PMID- 15464661
TI  - Liver disease due to parenteral and enteral nutrition.
AB  - Liver disease due to parenteral and enteral nutrition is a well-recognized
      iatrogenic phenomenon, but its cause and pathogenesis have not been clearly
      elucidated. Various mechanisms have been postulated, but it is likely that the
      cause is multifactorial with significant interplay among several factors. A
      preventive approach to management is ideal but awaits a more complete
      understanding of the pathophysiology. A variety of management strategies has been
      proposed in small case series, but level 1 evidence-based guidelines have yet to
      be established. Although an abundance of both clinical and animal studies exist
      regarding liver disease associated with parenteral nutrition (PN), there is a
      paucity of data regarding enteral nutrition (EN)-associated hepatic disease. The
      latter probably reflects differences in the frequency and severity of PN- versus
      EN-associated liver disease. This article addresses the two routes of nutritional
      support individually, with the major focus on PN-associated liver disease.

PMID- 15464662
TI  - Metabolic storage diseases: amyloidosis.
AB  - This article provides an overview of the current concepts in pathogenesis,
      epidemiology, clinical significance, and treatment options for amyloidosis.
      Emphasis is given to hepatic amyloidosis, which ranges from a clinically
      insignificant histologic curiosity to a harbinger of widespread disease
      accompanied by a poor prognosis. Clinical characteristics and clues to the
      diagnosis are discussed as well as the importance of histologic confirmation and
      the controversy surrounding liver biopsy.

PMID- 15464663
TI  - Relation of clinical success in coronary brachytherapy to dose.
AB  - Intravascular brachytherapy is the primary treatment for coronary in-stent
      restenosis. Variations in dose in the treated artery may represent a potential
      cause of treatment failure. We compared dose distributions in patients who had
      developed recurrent restenosis (treatment failure) with those in patients who
      remained event free at 9 months (treatment success). We followed 140 patients who
      were receiving brachytherapy for in-stent restenosis with 4 radiation delivery
      devices to identify treatment failures and successes. Through a nested case
      control construct, treatment failures (n = 14) were compared 1:2 with treatment
      successes (n = 28) matched by radiation delivery system and in-stent restenosis
      lesion pattern. The dose absorbed by 90% of the artery encompassed by the
      external elastic membrane (D(90)EEM) was calculated by applying intravascular
      ultrasound at 2-mm intervals along the treated lesion. Dose calculations were
      performed using dose kernel integration techniques generated from Monte Carlo
      simulations. The mean minimum D(90)EEM in treatment failures was 7.46 +/- 1.98
      Gy, and that in treatment successes was 8.87 +/- 1.13 Gy (p = 0.007). Using a
      minimum dose threshold of 8.4 Gy, a minimum D(90)EEM <or=8.4 Gy occurred in 13
      patients (93%) whose treatment failed but only in 9 patients (32%) whose
      treatment was a success (p <or=0.001). No confounding variables were found to be
      statistically significant between treatment failures and successes. In
      conclusion, current brachytherapy dose prescriptions allow for inter- and
      intralesion variations in dose. Arteries that receive <or=8.4 Gy at any point
      along the external elastic membrane are more likely to result in treatment
      failures. Dosimetry guided by intravascular ultrasound may be critical to ensure
      adequate dose delivery and outcomes.

PMID- 15464664
TI  - Utility of the Safe-Cross-guided radiofrequency total occlusion crossing system
      in chronic coronary total occlusions (results from the Guided Radio Frequency
      Energy Ablation of Total Occlusions Registry Study).
AB  - The Safe-Cross radiofrequency guidewire (IntraLuminal Therapeutics, Carlsbad,
      California) combines 3 capabilities: (1) steerability of a conventional 0.014-in
      intermediate-stiffness guidewire, (2) optical coherence reflectometry to warn the
      operator when the wire tip approaches within 1 mm of the vessel wall, and (3)
      delivery of radiofrequency energy pulses to the wire tip to facilitate passage
      through an occluded segment. The Guided Radio Frequency Energy Ablation of Total
      Occlusions Registry was a prospective, nonrandomized, multicenter registry that
      enrolled 116 patients who had long-term coronary total occlusions and in whom a
      >10-minute good-faith attempt to cross the occlusion using conventional
      guidewires had failed. The median known duration of occlusion was 22 months (32%;
      >1 year), and the median length of the occluded segment was 25 mm (25%; >30 mm).
      Device success was achieved in 63 of 116 of patients (54.3%), and major adverse
      events occurred in 6.9%, consisting predominantly of isolated increases in
      cardiac enzymes with no procedure-related deaths, Q-wave myocardial infarctions,
      or emergency bypass operations. Clinical perforation occurred in 2.6% of
      patients; of these, perforation in only 1 patient (0.9%) was adjudicated to be
      directly related to the Safe-Cross radiofrequency wire rather than to the stiff
      and/or hydrophilic wires used after an inability to advance with the Safe-Cross.
      Based on these data, the device has been approved in Europe and was recently
      (January 2004) granted 510K clearance by the Food and Drug Administration.

PMID- 15464665
TI  - ST-segment resolution 60 minutes after combination treatment of abciximab with
      reteplase or reteplase alone for acute myocardial infarction (30-day mortality
      results from the resolution of ST-segment after reperfusion therapy substudy).
AB  - The combination of abciximab with thrombolytic therapy when treating acute ST
      elevation myocardial infarction has been hypothesized to enhance microvascular
      perfusion. Resolution of ST-segment elevation after thrombolytic therapy is
      believed to be a marker of myocardial reperfusion and to predict mortality rate.
      Among 16,588 patients enrolled in the Fifth Global Use of Strategies to Open
      Occluded Arteries in Acute Myocardial Infarction trial, 1,764 consecutive
      patients from selected centers had their study electrocardiograms evaluated by a
      core laboratory for ST-segment deviation resolution 60 minutes after treatment.
      Patients were categorized into 4 groups: complete resolution (>70%), partial
      resolution (<70% to 30%), no resolution (<30%), and worsening ST-segment
      deviation. Patients treated with reteplase or a combination of reteplase plus
      abciximab had similar rates of complete resolution (32% vs 34%), partial
      resolution (29% vs 27%), no resolution (15% vs 16%), and worsening ST-segment
      elevation (23 vs 23%; p = 0.59). The 30-day mortality rates in these 4 groups
      were 2.1%, 5.2%, 5.5%, and 8.1% (p <0.001). Even after accounting for baseline
      variables, incomplete ST-segment resolution (<70%) was associated with an
      increased risk of death within 30 days (adjusted hazard ratio 2.41, 95%
      confidence interval 1.25 to 4.63, p <0.008). Thus, ST-segment resolution at 60
      minutes was no different in patients treated with full-dose reteplase from those
      treated with a combination of abciximab and reteplase. Patients with >70% ST
      segment resolution within 60 minutes had markedly decreased mortality rates,
      irrespective of treatment.

PMID- 15464666
TI  - A change in serum myoglobin to detect acute myocardial infarction in patients
      with normal troponin I levels.
AB  - We sought to determine the sensitivity of a change in myoglobin for acute
      myocardial infarction (AMI) in patients who had normal levels of troponin I at
      presentation. Myoglobin increases as soon as 1 to 2 hours after symptom onset in
      AMI. The change in myoglobin may help identify AMI in patients with normal
      cardiac levels of troponin I on admission. A total of 817 consecutive patients
      who were examined in the emergency department for possible AMI were studied. In
      patients whose electrocardiograms were nondiagnostic, we measured levels of
      myoglobin and cardiac troponin I at presentation, at 90 minutes, and at 3 and 9
      hours. Patients whose initial levels of myoglobin (<200 ng/ml) and cardiac
      troponin I (<0.4 ng/ml) were normal underwent receiver-operating characteristic
      curve analysis to determine the best cutpoint for a myoglobin increase from 0 to
      90 minutes. Overall, 75 patients (9%) were diagnosed with AMI, including 27
      patients with normal cardiac levels of troponin I at presentation. An increase of
      20 ng/ml of myoglobin from 0 to 90 minutes provided maximal diagnostic utility in
      patients who did not have increased levels of myoglobin or cardiac troponin I at
      presentation. In the absence of an increased level of cardiac troponin I or
      myoglobin at presentation in the emergency department, a change >or=20 ng/ml of
      myoglobin at 90 minutes produced 83.3% sensitivity, 88.6% specificity, and 99.5%
      negative predictive value for AMI. The combined sensitivity of levels of cardiac
      troponin I and myoglobin and a change >or=20 ng/ml of myoglobin over 90 minutes
      was 97.3%. In emergency department patients with normal cardiac levels of
      troponin I at presentation, a change in myoglobin provides a highly accurate
      diagnosis of AMI within 90 minutes.

PMID- 15464667
TI  - Comparison of ankle-brachial pressure index and pulse wave velocity as markers of
      the presence of coronary artery disease in subjects with a high risk of
      atherosclerotic cardiovascular disease.
AB  - Recently, a measurement device that can simultaneously measure the ankle-brachial
      pressure index (ABI) and brachial-ankle pulse wave velocity (PWV) has become
      available. The present study compares the applicability of ABI and PWV as markers
      for predicting the prevalence of coronary artery disease (CAD) in subjects with a
      high risk of atherosclerotic cardiovascular disease. The ABI and brachial-ankle
      PWV were measured in 472 consecutive subjects who subsequently underwent coronary
      angiography for diagnosis or exclusion of CAD. The prevalence of CAD in the
      lowest ABI quartile was higher than those in the other 3 ABI quartiles, whereas
      the prevalence in the lowest brachial-ankle PWV quartile was lower than those in
      the other 3 brachial-ankle PWV quartiles. A multivariate logistic regression
      analysis demonstrated that the lowest ABI quartile was a significant independent
      variable for the prevalence of CAD and that the lowest brachial-ankle PWV
      quartile was a significant independent variable for the absence of CAD in a
      population. Thus, a low ABI is an independent marker for an additive risk of CAD,
      whereas a low brachial-ankle PWV may be used as an independent marker for
      excluding the risk of CAD among subjects with a high risk of atherosclerotic
      cardiovascular disease.

PMID- 15464668
TI  - Impact of contemporary guideline compliance on risk stratification models for
      acute coronary syndromes in The Registry of Acute Coronary Syndromes.
AB  - We compared the predictive value of the Rush score with the Thrombolysis In
      Myocardial Infarction (TIMI) risk score in unselected patients with an acute
      coronary syndrome and evaluated the effect of compliance with established
      guidelines on the accuracy of these models. The Registry of Acute Coronary
      Syndromes is a retrospective registry of 3,754 consecutive patients (38% women;
      mean age 67 years) who presented with acute coronary syndrome to the emergency
      department between April 1, 1999, and December 31, 2000, at 9 hospitals. The
      primary end point was death, myocardial infarction, or urgent revascularization
      during hospitalization. Rush classification was based on quartiles of predicted
      risk of cardiac complication (<2% for class I vs >15% for class IV). The TIMI
      score was implemented as published. Compliance with guidelines for acute coronary
      syndrome was assessed with a 4-point scale based on the aggregate use of aspirin,
      beta blockers, heparin, and glycoprotein IIb/IIIa inhibitors. Fifteen percent of
      patients met the primary end point. The primary end point rates for TIMI scores
      0/1, 2, 3, 4, 5, and 6/7 were 11%, 14%, 13%, 11%, 14%, and 12%, respectively (p =
      NS). The primary end point rates for Rush classes I, II, III, and IV were 6%, 8%,
      9%, and 17%, respectively (p <0.001). After controlling for compliance with
      established guidelines, the odds ratio of an event increased by 46% for each unit
      increase in Rush score (p <0.001). After adjusting for the Rush score, the odds
      ratio decreased by 54% for each unit increase in compliance (p <0.001). Thus,
      compliance with current American College of Cardiology/American Heart Association
      guidelines significantly improves prognosis, regardless of the risk score. The
      use of established risk scores may overestimate event rates in unselected
      populations.

PMID- 15464669
TI  - Cardiac troponin T elevation after coronary artery bypass grafting is associated
      with increased one-year mortality.
AB  - The results of the present study extend the value of assessing troponin T for the
      prediction of mortality rate 1 year after coronary artery bypass grafting; this
      study supports previous work that demonstrated the value of postoperative
      assessment of troponin T for the prediction of in-hospital adverse outcome after
      coronary artery bypass grafting.

PMID- 15464670
TI  - Safety of rosuvastatin.
AB  - The safety and tolerability of rosuvastatin were assessed (as of August 2003)
      using data from 12,400 patients who received 5 to 40 mg of rosuvastatin in a
      multinational phase II/III program, which represented 12,212 patient-years of
      continuous exposure to rosuvastatin. An integrated database was used to examine
      adverse events and laboratory data. In placebo-controlled trials, adverse events,
      irrespective of causality assessment, occurred in 57.4% of patients who received
      5 to 40 mg of rosuvastatin (n = 744) and 56.8% of patients who received placebo
      (n = 382). In fixed-dose trials with comparator statins, 5 to 40 mg of
      rosuvastatin showed an adverse event profile similar to those for 10 to 80 mg of
      atorvastatin, 10 to 80 mg of simvastatin, and 10 to 40 mg of pravastatin.
      Clinically significant elevations in alanine aminotransferase (>3 times the upper
      limit of normal) and creatine kinase (>10 times the upper limit of normal) were
      uncommon (<or=0.2%) in the groups that received rosuvastatin and comparator
      statins. Myopathy (creatine kinase >10 times the upper limit of normal with
      muscle symptoms) that was possibly related to treatment occurred in <or=0.03% of
      patients who took rosuvastatin at doses <or=40 mg. A positive finding of
      proteinuria with dipstick testing at rosuvastatin doses <or=40 mg was comparable
      to that seen with other statins, and the development of proteinuria was not
      predictive of acute or progressive renal disease. No deaths in the program were
      attributed to rosuvastatin, and no rhabdomyolysis occurred in patients who
      received 5 to 40 mg of rosuvastatin. Rosuvastatin was well tolerated by a broad
      range of patients who had dyslipidemia, and its safety profile was similar to
      those of the comparator statins investigated in this extensive clinical program.

PMID- 15464671
TI  - Comparison of the impact of atrial fibrillation on the risk of stroke and
      cardiovascular death in women versus men (The Copenhagen City Heart Study).
AB  - The Copenhagen City Heart Study is a population-based cohort study. Using
      baseline data from 3 cohort examinations (1976 to 1978, 1981 to 1983, and 1991 to
      1994), we analyzed the gender-specific effect of atrial fibrillation (AF) on the
      risk of stroke and cardiovascular death during 5 years of follow-up. Baseline
      data from 29,310 subjects were included. AF was documented in 276 subjects (110
      women and 166 men). During a mean follow-up of 4.7 years, 635 strokes were
      identified, 35 of which occurred in subjects who had AF (22 women and 13 men).
      After adjustment for age and co-morbidity, the effect of AF on the risk of stroke
      was 4.6-fold greater in women (hazard ratio 7.8, 95% confidence interval 5.8 to
      14.3) than in men (hazard ratio 1.7, 95% confidence interval 1.0 to 3.0).
      Cardiovascular death occurred in 1,122 subjects, 63 of whom had AF (28 in women
      and 35 in men). The independent effect of AF on cardiovascular mortality rate was
      2.5-fold greater in women (hazard ratio 4.4, 95% confidence interval 2.9 to 6.5)
      than in men (hazard ratio 2.2, 95% confidence interval 1.6 to 3.1). Our results
      indicate that AF is a much more pronounced risk factor for stroke and
      cardiovascular death in women than in men.

PMID- 15464672
TI  - Determinants of atrial fibrillation development in patients with hypertrophic
      cardiomyopathy.
AB  - Predictors of the development of atrial fibrillation (AF) in patients who have
      hypertrophic cardiomyopathy (HC) have not been extensively studied, although, in
      these patients, AF contributes to the exacerbation of symptoms and the
      development of heart failure. The present study determined the role of left
      atrial (LA) function in the development of AF in patients who have HC. One
      hundred fifty consecutive patients who had HC, had no history of AF, and who were
      followed for 5.2 +/- 2.9 years constituted the study population. Using M-mode
      echocardiography, we measured LA function as global LA fractional shortening and
      LA diameter. LA volume was measured from 2-dimensional 4-chamber views by the
      method of disks. During follow-up, 20 patients developed AF. LA function was an
      independent predictor of AF (odds ratio 0.716, p = <0.001), whereas LA diameter
      and volume were predictors in addition to age. Kaplan-Meier analysis showed that
      LA dysfunction carried a high risk of AF. Thus, in patients who have HC, LA
      function is a strong predictor of AF development and is independent of age.

PMID- 15464673
TI  - Long-term cardiovascular risk with protease inhibitors and management of the
      dyslipidemia.
AB  - This report reviews current data pertaining to the development of dyslipidemia
      during treatment with protease inhibitors and the associated risk for
      cardiovascular disease in patients who have the human immunodeficiency virus.
      Most protease inhibitors used to manage the human immunodeficiency virus and the
      acquired immunodeficiency syndrome are associated with prompt, marked, and
      sustained increases in serum lipid levels that are consistent with an increased
      10-year risk for coronary heart disease as determined in the Framingham Heart
      Study. Management of lipid elevations in patients who use protease inhibitors is
      discussed. Novel protease inhibitors, which have minimal effects on lipid
      profiles, may have a role in the long-term management of the human
      immunodeficiency virus.

PMID- 15464675
TI  - Effectiveness of sirolimus-eluting stent implantation for the treatment of
      coronary artery disease in octogenarians.
AB  - Sirolimus-eluting stent (SES) implantation has been shown to reduce repeat
      revascularization in various randomized trials. The present study evaluated the
      outcomes after SES implantation in 46 octogenarian patients. SES implantation in
      octogenarians appears to be feasible and is associated with very small subsequent
      need for repeat target vessel revascularization at 1 year.

PMID- 15464674
TI  - Acute angiographic analysis of non-ST-segment elevation acute myocardial
      infarction.
AB  - Most revascularization studies on acute myocardial infarction have included
      patients who have ST-segment elevation or new-onset left bundle branch block.
      However, the characteristics of patients who have non-ST-segment elevation acute
      myocardial infarction and who have undergone angiographic analysis of their
      infarct-related arteries have not been adequately described. This study suggests
      that these patients are likely to have had coronary bypass surgery (odds ratio
      4.58, 95% confidence interval 1.83 to 11.5, p = 0.0012) and that circumflex
      artery occlusions are more likely to present as non-ST-segment elevation than as
      acute myocardial infarction with ST-segment elevation and/or left bundle branch
      block (odds ratio 2.91, 95% confidence interval 1.62 to 5.22, p = 0.0003).

PMID- 15464677
TI  - Comparison of acute and long-term results and underlying mechanisms from
      sirolimus-eluting stent implantation for the treatment of in-stent restenosis and
      recurrent in-stent restenosis in patients in whom intracoronary radiation failed
      as assessed by intravascular ultrasound.
AB  - In-stent restenosis (ISR), especially after vascular brachytherapy, is a
      therapeutic challenge. Sirolimus-eluting stent implantation is a promising new
      option for the treatment of patients with ISR. The efficacy of sirolimus-eluting
      stent implantation for the treatment of patients with their first episodes of ISR
      and with recurrent ISR due to the failure of vascular brachytherapy was compared
      using intravascular ultrasound imaging.

PMID- 15464676
TI  - Simultaneous kissing stents (SKS) technique for treating bifurcation lesions in
      medium-to-large size coronary arteries.
AB  - The treatment of bifurcation lesions (BLs) is associated with high procedural
      complication and restenosis rates. Two techniques of BL interventions were
      compared: the simultaneous kissing stents (SKS) technique, involving 2 stents, 1
      in the main vessel and 1 in the side branch (n = 100), and the conventional stent
      strategy (CSS) technique, involving a stent in the main vessel and provisional
      stenting for the side branch (n = 100). In-hospital and 30-day major adverse
      cardiac events were greater in the CSS group, with significantly less procedure
      time with the SKS technique. The incidence of target lesion revascularization was
      5% in the SKS group and 18% in the CSS group (p = 0.007). Therefore, the SKS
      technique seems to be rapid, safe, and effective for the treatment of medium- to
      large-size BLs, with a trend toward fewer acute complications and promising mid
      term results.

PMID- 15464678
TI  - Usefulness of high-pressure post-dilatation to optimize deployment of drug
      eluting stents for the treatment of diffuse in-stent coronary restenosis.
AB  - Drug-eluting stents (DESs) may represent a simple, effective treatment for in
      stent restenosis (ISR); however, the underexpansion of stents is a significant
      cause of target vessel failure. It was hypothesized that high-pressure
      postdilatation would be necessary to optimize DES expansion and minimize the risk
      for restenosis when treating patients with ISR. Fifteen patients with diffuse ISR
      were treated by predilatation (including cutting balloons), DES deployment, and
      high-pressure postdilatation, with the measurement of luminal and stent
      dimensions by intravascular ultrasound after each intervention. After initial
      deployment, DES underexpansion was present in 10 of 15 patients (66%); after high
      pressure postdilatation, there was a significant increase in luminal dimensions,
      including minimum luminal area (4.3 +/- 0.3 to 5.6 +/- 0.4 mm(2), p <0.001) and a
      doubling in the proportion of patients with optimal stent expansion. At long-term
      follow-up (median 11 months), target lesion revascularization occurred in 1
      patient (7%) because of edge restenosis; there was no restenosis within the DES.

PMID- 15464679
TI  - Optimal duration of eptifibatide infusion in percutaneous coronary intervention
      (an ESPRIT substudy).
AB  - Although randomized trials have clearly demonstrated the clinical efficacy with
      regimens of platelet glycoprotein IIb/IIIa antagonists that result in >80%
      inhibition of baseline platelet aggregation in percutaneous coronary intervention
      (PCI), there are no data available concerning the optimal duration of infusion of
      these agents. In an era when the length of hospitalization has a major impact on
      health care costs, the determination of the optimal duration of the infusion of
      these drugs after PCI is of great relevance. The investigators therefore sought
      to determine the optimal length of the infusion of eptifibatide after PCI by
      analyzing the outcomes of patients enrolled in the Enhanced Suppression of the
      Platelet IIb/IIIa Receptor With Integrilin Therapy trial who were randomized to
      treatment with eptifibatide.

PMID- 15464680
TI  - Evaluation of whole left ventricular systolic performance and local myocardial
      systolic function in patients with prior myocardial infarction using global long
      axis myocardial strain.
AB  - Left ventricular (LV) global strain along its long axis during systole, which is
      obtained by dividing mitral annular excursion by the distance from the mitral
      annulus to the LV apex at end-diastole, can be used to assess whole LV systolic
      performance. The evaluation of LV wall function using this parameter suggests
      that previous myocardial infarction (MI) causes long-axis myocardial function in
      remote normal LV walls, as well as in walls with MI, to deteriorate.

PMID- 15464681
TI  - Effect of hyperuricemia upon endothelial function in patients at increased
      cardiovascular risk.
AB  - The aim of the present study was to evaluate the effect of increased serum uric
      acid (UA) levels and their therapeutic reduction with allopurinol on endothelium
      dependent dilation in subjects with a high cardiovascular (CV) risk but who were
      free from clinical CV disease. Patients with hyperuricemia had impaired flow
      mediated dilation (FMD) compared with matched controls with normal UA levels and
      elevated CV risk. Three-month therapy with allopurinol improved FMD in
      hyperuricemic subjects, showing an intrinsic negative effect of elevated UA
      levels on the arterial wall; conversely, FMD remained unchanged in controls, thus
      suggesting that the reduction of UA to less than a certain value does not affect
      endothelial function.

PMID- 15464682
TI  - Risk of adverse events with fibrates.
AB  - An increased risk for adverse events was observed with gemfibrozil relative to
      fenofibrate, predominantly driven by an increased rate of rhabdomyolysis. This
      difference was especially noticeable in patients taking the combination of
      gemfibrozil and a statin, particularly cerivastatin.

PMID- 15464683
TI  - Effects of ventricular rate regularization pacing on quality of life and symptoms
      in patients with atrial fibrillation (Atrial fibrillation symptoms mediated by
      pacing to mean rates [AF SYMPTOMS study]).
AB  - The aim of this study was to investigate the effect of the Ventricular Response
      Pacing (VRP) algorithm, which regularizes ventricular rate during atrial
      fibrillation (AF), on symptoms, quality of life, and functional capacity. VRP
      regularizes the ventricular rate during AF without increasing the mean
      ventricular rate, thereby reducing the severity of AF-related symptoms in
      patients with persistent AF. However, VRP did not improve general quality of life
      (Medical Outcomes Study 36-item Short-Form General Health Survey), the
      performance of routine activities (Duke Activity Status Index), or functional
      capacity (hall walk) in patients with AF.

PMID- 15464684
TI  - Simultaneous biplane single-beat assessment of left ventricular systolic function
      in patients with atrial fibrillation.
AB  - Left ventricular systolic function was studied in 40 patients with atrial
      fibrillation using a matrix-array transducer, which enables 2 simultaneous
      orthogonal views to be obtained in a biplane mode. Bland-Altman analysis showed
      excellent correlation and agreement between the systolic parameters of a single
      beat with identical RR1 and RR2 intervals and the measured average value over all
      cardiac cycles.

PMID- 15464685
TI  - Circumferential pulmonary vein ablation for treatment of atrial fibrillation
      using an irrigated-tip catheter.
AB  - In this study, a series of 52 consecutive patients with atrial fibrillation from
      1 institution underwent circumferential pulmonary vein ablation using an
      irrigated-tip catheter. The technique was safe, and 81% of the patients
      maintained sinus rhythm at 6 months. However, 1/3 of them required additional
      antiarrhythmic drug therapy.

PMID- 15464686
TI  - Warfarin and aspirin use and the predictors of major bleeding complications in
      atrial fibrillation (the Framingham Heart Study).
AB  - The Framingham Heart Study records of participants with atrial fibrillation (AF)
      during 1980 and 1994 were retrospectively reviewed to determine the prevalence of
      warfarin and aspirin use in AF. Anticoagulant use increased significantly in the
      393 men and women (mean ages 72.5 and 79.0 years, respectively) who developed AF
      over the observation period: aspirin use increased from 14% to 39% in men and
      from 19% to 33% in women, and warfarin use increased from 10% to 39% in men and
      from 17% to 38% in women. There were no significant gender differences in
      anticoagulant use (p = 0.61), but participants using warfarin were younger. A
      total of 65 participants (17%) had major bleeding complications <or=5 years after
      initial AF. Age was not a significant predictor of bleeding.

PMID- 15464687
TI  - Usefulness of intracardiac Doppler assessment of left atrial function immediately
      post-pulmonary vein antrum isolation to predict short-term recurrence of atrial
      fibrillation.
AB  - Doppler assessments of pulmonary venous (PV) and left atrial appendage flows are
      useful surrogates of left atrial (LA) function, but it is unknown if these can
      predict atrial fibrillation (AF) recurrence after pulmonary vein antrum
      isolation. We compared Doppler surrogates of LA function immediately after
      pulmonary vein antrum isolation in patients with AF recurrence versus matched
      patients without recurrence. Patients with a 6-month recurrence had significantly
      lower LA appendage peak emptying velocity (19 +/- 10 vs 29 +/- 11 cm/s) and lower
      peak PV systolic wave velocity (36 +/- 17 vs 46 +/- 22 cm/s) compared with those
      without, suggesting that intracardiac Doppler assessment of LA function after AF
      ablation predicts AF recurrence.

PMID- 15464688
TI  - Prognostic stratification of patients with right bundle branch block using
      dobutamine stress echocardiography.
AB  - The presence of a right bundle branch block (RBBB) is associated with increased
      mortality. We studied the role of dobutamine stress echocardiography for the
      prognostic stratification of patients with RBBB. The presence of an abnormal
      dobutamine stress echocardiography was the strongest predictor of cardiac events
      and provided incremental prognostic information to clinical and stress test data.

PMID- 15464689
TI  - Effect of elevated admission serum creatinine and its worsening on outcome in
      hospitalized patients with decompensated heart failure.
AB  - Renal insufficiency (RI), as represented by elevated serum creatinine (>1.5
      mg/dl) on admission, is common and found in almost half of patients hospitalized
      with decompensated heart failure. This finding is associated with prolongation of
      length of stay and rate of rehospitalizations after discharge and also has an
      independent unfavorable effect on 6-month mortality. Similarly, an increase in
      serum creatinine (>0.5 mg/dl) in the hospital results in a significantly longer
      length of stay and has an independent effect on long-term mortality.

PMID- 15464690
TI  - Usefulness of spatial dispersion of QRS duration in predicting mortality in
      patients with mild to moderate chronic heart failure.
AB  - To prospectively evaluate the prognostic significance of spatial dispersion of
      QRS duration (S-QRSd) on a signal-averaged electrocardiogram in patients with
      chronic heart failure (CHF), we studied 114 consecutive stable outpatients with
      radionuclide left ventricular ejection fraction <40%. Cardiac and sudden deaths
      were significantly more often observed in patients with than without abnormal S
      QRSd. S-QRSd is a powerful prognostic marker of the mortality in patients with
      mild to moderate CHF.

PMID- 15464691
TI  - Usefulness of real-time three-dimensional echocardiography for evaluation of
      myectomy in patients with hypertrophic cardiomyopathy.
AB  - Real-time 3-dimensional echocardiography was performed in 10 patients with
      obstructive hypertrophic cardiomyopathy (HC) before and after myectomy and in 6
      controls. The exact location of systolic anterior motion of the mitral leaflet
      was shown in all patients with HC with a predominant involvement of the medial
      portion in 4 patients and the middle portion in 6 patients. The smallest area of
      the left ventricular outflow tract was significantly smaller in patients with HC
      than in controls (1.4 +/- 0.7 vs 5.1 +/- 1.2 cm(2), p <0.01), significantly
      increased after myectomy (4.8 +/- 1.8 cm2, p <0.01) and was associated with a
      reduction of the pressure gradient at rest from 63 +/- 41 to 15 +/- 5 mm Hg (p
      <0.01).

PMID- 15464692
TI  - Usefulness of multislice computed tomography angiography to evaluate
      intravascular stents and transcatheter occlusion devices in patients with d
      transposition of the great arteries after mustard repair.
AB  - Percutaneous interventions can treat long-term complications after Mustard atrial
      switch operation in patients with d-transposition of the great arteries (d-TGA),
      but follow-up for these procedures has not been established. Four patients with d
      TGA and previous Mustard operation underwent percutaneous placement of covered
      stents to relieve superior and inferior vena caval baffle obstructions and leaks.
      At 6 to 13 months, assessment with 16-slice spiral computed tomography identified
      stent patency as well as lead placement and visualization of additional devices.

PMID- 15464693
TI  - Regional differences in right ventricular systolic function as determined by cine
      magnetic resonance imaging after infundibulotomy.
AB  - The right ventricle of subjects after infundibulotomy (n = 20) and of subjects
      free of right ventricular disease (n = 19) was partitioned into the infundibular
      and sinus segments to examine the relative size and function of each. Excellent
      agreement was found between observers for measuring regional volume and ejection
      fraction. Although the surgical subjects had lower infundibular ejection fraction
      and higher indexed volumes, most had preserved sinus ejection fraction.

PMID- 15464694
TI  - Recurrent pain without objective evidence of disease in patients with previous
      idiopathic or viral acute pericarditis.
AB  - Recurrent pain without clinical evidence of acute pericarditis was recorded in 27
      of 275 patients (9.8%; mean age 55.6 +/- 16.0 years, female/male ratio 20/7) with
      previous viral or idiopathic acute pericarditis. Female gender (odds ratio [OR]
      4.3, 95% confidence interval [CI] 1.8 to 10.6), previous use of corticosteroids
      (OR 5.2, 95% CI 2.2 to 12.3), and previous recurrent pericarditis (OR 3.7, 95% CI
      1.3 to 10.2) were identified as risk factors for this syndrome. After a mean
      follow-up of 40 months, a higher recurrence rate was recorded in these patients
      (33.3% vs 14.1%; p = 0.02) as well as a nonsignificant trend to a higher rate of
      constrictive pericarditis.

PMID- 15464695
TI  - Association of aspirin use with vitamin B12 deficiency (results of the BACH
      study).
AB  - We examined the prevalence of vitamin B(12) deficiency and its association with
      medication use and characteristics, including infection with Helicobacter pylori
      (H. pylori), in 255 patients hospitalized for cardiovascular disease. In almost
      half of the study population, vitamin B(12) deficiency was found; patients using
      acetylsalicylic acid were more frequently vitamin B(12) deficient in comparison
      to nonusers (p = 0.02). Fifty-one percent of the patients were infected with H.
      pylori, and fewer infected patients were vitamin B(12) deficient.

PMID- 15464696
TI  - Prevalence of diabetes mellitus and related conditions in Asian Indians living in
      the United States.
AB  - This study is the first attempt to evaluate the prevalence of diabetes mellitus
      and related conditions in Asian Indians living in the United States. A community
      based survey of 1,046 Asian Indian immigrants living in and around the Atlanta
      metro area of Georgia was conducted and found an overall prevalence of diabetes
      mellitus of 18.3% (22.5% in men and 13.6% in women). This prevalence of diabetes
      mellitus in Asian Indians is much higher than in whites, blacks, and Hispanics
      living in the United States.

PMID- 15464697
TI  - Wake up and smell the caffeine.

PMID- 15464698
TI  - High iron stores and ischemic heart disease in rheumatoid arthritis and systemic
      lupus erythematosus.

PMID- 15464699
TI  - Apical hypertrophic cardiomyopathy in Japan and the United States in brothers but
      not identical twins.

PMID- 15464700
TI  - Conservative management of complete heart block complicating percutaneous
      transluminal septal myocardial ablation for patients with obstructive
      hypertrophic cardiomyopathy.

PMID- 15464701
TI  - Association of beta-adrenergic receptor polymorphisms and progression to heart
      failure in patients with idiopathic dilated cardiomyopathy.
AB  - PURPOSE: Increased sympathetic nervous system activation via the beta-adrenergic
      pathway influences the evolution of idiopathic dilated cardiomyopathy. We
      assessed the effects of beta-adrenergic receptor variants on heart failure in
      idiopathic dilated cardiomyopathy. METHODS: We prospectively analyzed 171
      consecutive patients (mean [+/- SD] age, 49 +/- 14 years; 129 men) with
      idiopathic dilated cardiomyopathy who were receiving conventional treatment. All
      were characterized by polymerase chain reaction-restriction fragment length
      polymorphism analysis for Ser49Gly and Arg389Gly in the beta1-adrenergic
      receptor; the 5' leader cistron (LC) Arg19Cys, Arg16Gly, Gln27Glu, and Thr164Ile
      in the beta2-adrenergic receptor; and Arg64Trp in the beta3-adrenergic receptor.
      The endpoint was heart failure, defined as a worsening of clinical condition
      leading to hospitalization for heart failure, cardiac transplantation, or death
      from heart failure. RESULTS: During a median follow-up of 33 months, 24 patients
      had heart failure. In a Cox univariate analysis, the beta1Gly49 and beta2 5'LC
      Cys19, Arg16, and Gln27 alleles were associated with a lower risk of heart
      failure. In a multivariate analysis that considered age, functional class, left
      ventricular ejection fraction, and beta-blocker use, three beta2-adrenergic
      receptor alleles were associated with lower risk: 5'LC-Cys19 (hazard ratio [HR]:
      0.15; 95% confidence interval [CI]: 0.05 to 0.42), Arg16 (HR: 0.12; 95% CI: 0.04
      to 0.35), and Gln27 (HR: 0.15; 95% CI: 0.05 to 0.42). CONCLUSION: The Gly49
      allele in the beta1-adrenergic receptor and the 5' LC-Cys19, Arg16, and Gln27
      alleles in the beta2-adrenergic receptor were associated with a lower risk of
      heart failure in idiopathic dilated cardiomyopathy, suggesting that the beta1-
      and beta2-adrenergic receptor genes are modifier genes.

PMID- 15464702
TI  - Application of U.S. guidelines in other countries: aspirin for the primary
      prevention of cardiovascular events in Japan.
AB  - PURPOSE: Clinical guidelines developed in the United States are used frequently
      in other countries without assessment of their appropriateness in non-U.S.
      populations. We explored the relevance of recent U.S. guidelines for the use of
      aspirin for the primary prevention of cardiovascular events in the Japanese
      population. METHODS: From a systematic search of published data, estimates were
      derived for rates of coronary heart disease, hemorrhagic stroke, and major
      gastrointestinal bleeding for the Japanese population and for subgroups with
      different risk factors. Odds ratios derived from meta-analyses were used to
      assess the potential benefits and risks of aspirin use. RESULTS: The estimated
      incidence of coronary heart disease in middle-aged men in Japan is lower than in
      the United States (1.57 vs. 6.0 per 1000 person-years), while that of hemorrhagic
      stroke is higher (1.14 vs. 0.37 per 1000 person-years). Because of higher
      baseline rates of hemorrhagic diseases, the expected reduction in cardiovascular
      events with aspirin use would be offset by a greater increase in hemorrhagic
      complications for women and most men in Japan, except for those with both
      hypertension and diabetes. To achieve the same 2:1 ratio of coronary heart
      disease events avoided to hemorrhagic events caused that is implied by the 3%
      threshold for 5-year coronary disease risk in U.S. guidelines, a 6% to 14% risk
      threshold, depending on patient age, seems appropriate for recommending aspirin
      in Japanese patients. CONCLUSION: The thresholds of antiplatelet therapy for
      Asian populations should be two to five times higher than those for the U.S.
      population because of higher risks of hemorrhagic complications. The assumptions
      and implications of U.S. guidelines should be evaluated before use in other
      countries.

PMID- 15464703
TI  - Blunted circadian variation in autonomic regulation of sinus node function in
      veterans with Gulf War syndrome.
AB  - PURPOSE: To test the hypothesis that subtle abnormalities of the autonomic
      nervous system underlie the chronic symptoms reported by many Gulf War veterans,
      such as chronic diarrhea, dizziness, fatigue, and sexual dysfunction. METHODS:
      Twenty-two ill Gulf War veterans and 19 age-, sex-, and education-matched control
      veterans underwent measurement of circadian rhythm of heart rate variability by
      24-hour electrocardiography, ambulatory blood pressure recording, Valsalva ratio
      testing, sympathetic skin response evaluation, sweat imprint testing, and
      polysomnography. Investigators were blinded to case- or control-group status.
      RESULTS: High-frequency spectral power of heart rate variability increased
      normally 2.2-fold during sleep in controls but only 1.2-fold in ill veterans (P
      <0.0001). In ill veterans as compared with controls, it was lower at night (P =
      0.0006), higher during the morning (P = 0.007), but no different during the rest
      of the day (P = 0.8). The mean heart rate of ill veterans also declined less at
      night (P = 0.0002), and their corrected QT intervals tended to be longer over the
      full 24 hours (P = 0.07), particularly at night (P = 0.03). Blunting of the
      nocturnal heart rate dip in ill veterans was confirmed by 24-hour automatic
      ambulatory blood pressure monitoring (P = 0.05) and polysomnography (P = 0.03).
      These differences remained significant after adjusting for potential confounders.
      Cases and controls were similar on measures of sympathetic adrenergic and
      sudomotor function, sleep architecture, respiratory function, and circadian
      variation in blood pressure and body temperature. CONCLUSION: Some symptoms of
      Gulf War syndrome may be due to subtle autonomic nervous system dysfunction.

PMID- 15464704
TI  - Effects of increased primary care access on process of care and health outcomes
      among patients with asthma who frequent emergency departments.
AB  - PURPOSE: Many asthmatic patients discharged from emergency departments do not
      have timely follow-up visits with a primary care physician. This study was
      conducted to determine the effectiveness of a health professional-based
      intervention in improving process of care and health outcomes among asthmatic
      patients discharged from emergency departments. METHODS: We enrolled 125
      asthmatic patients, aged 5 through 50 years, from the emergency department of a
      community-based hospital; 62 patients were assigned to usual care and 63 to
      enhanced care. Enhanced care consisted of usual care plus employment of a
      coordinator to make follow-up appointments with the patient's primary care
      physician with at least one reminder telephone call to the patient. RESULTS: At 6
      months of follow-up, mean (+/- SD) asthma and pediatric quality-of-life scores
      were higher in the enhanced care group than in the usual care group (5.7 +/- 1.2
      units vs. 5.0 +/- 1.3 units, P = 0.01). The enhanced care group also had a higher
      rate of follow-up office visits (78% [n = 44] vs. 60% [n = 33], P = 0.003), were
      more likely to have written action plans (46% [n = 26] vs. 25% [n = 14], P =
      0.02), and had fewer asthma symptoms (1.8 +/- 1.1 units vs. 2.2 +/- 1.3 units, P
      = 0.09). However, these differences disappeared by 12 months of follow-up.
      CONCLUSION: A simple intervention wherein a health professional facilitates
      follow-up visits can improve the process of care and health outcomes of high-risk
      asthmatic patients. However, the effect of this intervention is time limited and
      largely wears off by 12 months.

PMID- 15464705
TI  - The development of insidious disability in activities of daily living among
      community-living older persons.
AB  - PURPOSE: To determine how often disability in essential activities of daily
      living develops insidiously, and to evaluate whether the likelihood of insidious
      disability differs on the basis of physical frailty. METHODS: We conducted a
      prospective study of 754 nondisabled, community-living persons aged 70 years or
      older. Participants were categorized according to the presence or absence of
      physical frailty, which was defined on the basis of gait speed. Participants were
      subsequently followed with monthly telephone interviews for 3 years to determine
      the occurrence of disability in bathing, dressing, walking, or transferring, and
      to ascertain exposure to precipitating events, which included acute hospital
      admissions and other illnesses, injuries, or problems leading to restricted
      activity. RESULTS: For first episodes of disability, 73 (36%) of 203 developed
      insidiously among the 322 participants who were physically frail and 26 (18%) of
      141 developed insidiously among the 432 participants who were not physically
      frail (P <0.001). Physical frailty was the only factor that was associated
      significantly with the development of insidious disability, with an adjusted odds
      ratio of 2.4 (95% confidence interval: 1.4 to 4.1). The likelihood that an
      episode of disability was insidious increased progressively, from 29% of the 344
      first episodes to 65% of the 155 fourth or higher episodes (P for trend <0.001).
      CONCLUSION: Disability in essential activities of daily living often occurs
      insidiously, particularly among older persons who are physically frail or who
      have had prior episodes of disability.

PMID- 15464706
TI  - Death certificate completion: how well are physicians trained and are
      cardiovascular causes overstated?
AB  - PURPOSE: To determine the ability of residents in completing death certificates
      correctly. METHODS: A total of 4800 residents were asked to complete a survey and
      cause-of-death statement using a sample case of in-hospital death due to
      urosepsis, of whom 590 residents (12%) responded. A scoring scale designed based
      on instructions from the National Association of Medical Examiners and the
      American College of Pathologists was used to measure responses quantitatively.
      RESULTS: Overall performance was poor, with only 23% (n = 137) of responses in
      the optimal scoring range. The average score was influenced significantly by
      level of residency training, as well as previous experience, prior formal
      training, and awareness of the guidelines regarding death certificate completion.
      Optimal scores correlated with level of residency training and prior formal
      training in death certificate completion, suggesting the benefits of experience
      and instruction. Forty-five percent (n = 267) of respondents incorrectly
      identified a cardiovascular event as the primary cause of death. CONCLUSION: The
      residents in this study demonstrated suboptimal performance in death certificate
      completion. Cardiovascular events were often incorrectly identified as the
      primary cause of death. Formal training can improve performance and should be
      emphasized in medical schools and residencies.

PMID- 15464707
TI  - C-reactive protein: from innocent bystander to pivotal mediator of
      atherosclerosis.
AB  - There is compelling evidence that C-reactive protein is a sensitive marker for
      the development of cardiovascular disease in the general population. Recent
      studies suggest that C-reactive protein is not only a biomarker but also an
      active mediator in the pathogenesis of atherosclerosis. We review the evidence
      and suggest mechanisms by which C-reactive protein can damage arterial
      endothelium and promote the development of atherosclerotic lesions, including the
      effects of C-reactive protein on arterial endothelial activation, macrophage
      recruitment, and foam cell generation. The direct role of C-reactive protein in
      sustaining a proinflammatory and procoagulant milieu within the arterial
      neointima is emphasized. We also discuss the evidence that C-reactive protein can
      injure arterial endothelium. Finally, we review therapies that target C-reactive
      protein for primary prevention and for the treatment of atherosclerotic diseases.

PMID- 15464708
TI  - Adverse effects of thalidomide administration in patients with neoplastic
      diseases.
AB  - Thalidomide, a glutamic acid derivative, was withdrawn from clinical use in 1962
      due to its severe teratogenic effects. Its recent reinstitution in clinical
      practice was related to its benefits in leprosy and multiple myeloma. Moreover,
      the antiangiogenic and immunomodulatory properties of thalidomide have led to its
      evaluation in several malignant diseases, including myelofibrosis, renal cell
      cancer, prostate cancer, and Kaposi sarcoma. However, thalidomide use is
      associated with several side effects: somnolence and constipation are the most
      common, while deep vein thrombosis and peripheral neuropathy are the most
      serious. A combination of thalidomide with steroids or chemotherapy is being
      evaluated in several phase 2 studies. While it is not yet clear whether these
      combinations will enhance efficacy, they appear to increase the toxicity of
      thalidomide, and thalidomide analogs are being developed to minimize this
      toxicity. Ongoing studies will clarify the potential advantages of these agents
      in the treatment of neoplastic diseases.

PMID- 15464709
TI  - Necrotizing vasculitis associated with familial Mediterranean fever.

PMID- 15464710
TI  - Low sensitivity of ultrasonography for the early diagnosis of amebic liver
      abscess.

PMID- 15464711
TI  - Cases from the Osler Medical Service at Johns Hopkins University. Cryptosporidium
      parvum.

PMID- 15464712
TI  - Polymorphisms of beta-adrenergic receptors in heart failure.

PMID- 15464713
TI  - Assessing the risk/benefit profile before recommending aspirin for the primary
      prevention of cardiovascular events.

PMID- 15464714
TI  - Cardiac autonomic dysfunction in Gulf War syndrome: veterans' hearts don't rest
      at night.

PMID- 15464715
TI  - Hypercalcemia in isolated hypothalamic-pituitary Langerhans cell histiocytosis
      with no bone lesions.

PMID- 15464717
TI  - Systematic reviews of herbal medicines.

PMID- 15464718
TI  - Dyspnea in a woman with a permanent pacemaker.

PMID- 15464719
TI  - Caring for our future selves.

PMID- 15464720
TI  - The metal-binding motif of dipeptidyl peptidase III directly influences the
      enzyme activity in the copper derivative of dipeptidyl peptidase III.
AB  - The zinc-binding motif (HELLGH) of dipeptidyl peptidase III (DPP III) is
      different from the common zinc-binding motif (HExxH) of metallopeptidases. To
      clarify the importance of the zinc-binding motif part of DPP III for enzymatic
      activity, we measured the recovery of the enzyme activity of apo-Leu(453)-deleted
      dipeptidyl peptidase III (apo-Leu(453)-del-DPP III), which has a motif (HELGH)
      like that of the common peptidase (HExxH), in the presence of various metal ions.
      The enzyme activity of apo-Leu(453)-deleted DPP III could not be recovered by the
      addition of cupric ions, while apo-DPP III could be easily reactivated by the
      addition of cupric ions. The visible and electron paramagnetic resonance spectra
      of the isolated Cu(II)-Leu(453)-del DPP III clearly show that the cupric ions of
      Cu(II)-Leu(453)-del-DPP III bound to the motif part (HELGH) but did not exhibit
      any enzyme activity. The motif part of DPP III directly influences the expression
      of the enzyme activity in the copper derivative of DPP III. The competitive
      inhibitor that is not at all digested by DPP III, Hisprophen (His-Pro-Phe-His-Leu
      d-Leu-Val-Tyr), has been determined. The inhibition constant (K(i)) of Hisprophen
      for DPP III or Cu(II)-DPP III was 4.1x10(-5) or 3.8x10(-5)M, respectively. In the
      presence of the competitive peptide inhibitor, Hisprophen, the EPR spectra of
      Cu(II)-DPP III were completely different from that of Cu(II)-DPP III itself. This
      result clearly indicates that the metal ions of DPP III are located in the active
      site and directly interact with the substrate.

PMID- 15464721
TI  - Identification of three phosphorylation sites in the alpha7 subunit of the yeast
      20S proteasome in vivo using mass spectrometry.
AB  - The 26S proteasome complex, which consists of a 20S proteasome and a pair of 19S
      regulatory particles, plays important roles in the degradation of ubiquitinated
      proteins in eukaryotic cells. The alpha7 subunit of the budding yeast 20S
      proteasome is a major phosphorylatable subunit; serine residue(s) in its C
      terminal region are phosphorylated in vitro by CKII. However, the exact in vivo
      phosphorylation sites have not been identified. In this study, using electrospray
      ionization quadrupole time-of-flight mass spectrometry analysis, we detected a
      mixture of singly, doubly, and triply phosphorylated C-terminal peptides isolated
      from a His-tagged construct of the alpha7 subunit by nickel-immobilized metal
      affinity chromatography. In addition, we identified three phosphorylation sites
      in the C-terminal region using MS/MS analysis and site-directed mutagenesis:
      Ser258, Ser263, and Ser264 residues. The MS/MS analysis of singly phosphorylated
      peptides showed that phosphorylation at these sites did not occur successively.

PMID- 15464722
TI  - Unequivocal estrogen receptor-binding affinity of phthalate esters featured with
      ring hydroxylation and proper alkyl chain size.
AB  - The effect of plasticizers phthalate esters (PEs) on health is a controversial
      subject. PEs are likely to be estrogenic, but the results on the potency obtained
      by many investigators are still inconsistent and the endocrine disrupting
      mechanism remains to be clarified. Here, we show that PEs acquire unequivocal
      binding affinities for human estrogen receptors (ERs) through ring hydroxylation
      that is possible in the environment and through metabolism. Unexpectedly, the
      acquired affinities of hydroxylated PEs (PEs-OH) were enhanced by elongation and
      branching of the ester alkyl chains. PEs-OH with alkyl chains more than six
      carbons may grope for a new binding site, which is inaccessible to PEs-OH with
      short chains. The strongest ER-binding affinity among the tested PEs-OH was close
      to that of diethylstilbestrol, the most potent synthetic ER-binder. Ring
      hydroxylation would be a new clue to the clarification of the endocrine
      disruption mechanism of PEs.

PMID- 15464723
TI  - Flavonoid biosynthesis in the tea plant Camellia sinensis: properties of enzymes
      of the prominent epicatechin and catechin pathways.
AB  - Leaves of tea (Camellia sinensis L.) contain extraordinary large amounts of (-)
      epigallocatechin, (-)-epicatechin, (+)-gallocatechin, and (+)-catechin and
      derivatives of these compounds that show positive effects on human health. The
      health-promoting effects of flavan 3-ols, especially those of green tea, are of
      scientific and public interest. Furthermore, they play a crucial role in defense
      against pathogens of tea. Therefore, biosynthesis of these flavonoid compounds
      was investigated. The anthocyanidin reductase enzyme recently described from
      Arabidopsis and Medicago was shown to be present in tea with very high activity
      and produces epicatechin as well as epigallocatechin from the respective
      anthocyanidins, thus explaining the very high contents of these compounds. A
      strong combined dihydroflavonol 4-reductase/leucoanthocyanidin 4-reductase
      activity was demonstrated and catalyzes the key steps in catechin and
      gallocatechin formation. Together with the enzyme activities and substrate
      specificities of the preceding enzymatic reactions, the biosynthesis of the most
      prominent flavonoids of tea is elucidated.

PMID- 15464724
TI  - Kidney ischemia-reperfusion regulates expression and distribution of tubulin
      subunits, beta-actin and rho GTPases in proximal tubules.
AB  - Ischemic injury is characterized by a loss of cell polarity and a release of
      proximal tubule epithelial cells resulting from cytoskeletal reorganization. This
      study used a reversible unilateral renal ischemia-reperfusion model to
      investigate the expression and distribution of cytoskeletal components and Rho
      GTPases at protein and mRNA levels in proximal tubule fractions. Ischemia
      strongly increased beta-actin and alpha-tubulin expressions that were
      predominantly found in nuclear fractions. Rho GTPases and caveolin-1 expression
      were upregulated by ischemia and were enriched mainly in Triton-soluble
      membranes. Rac1 expression was stimulated in the soluble fractions during
      reperfusion. Rho GTPases mRNA levels were similarly regulated by ischemia
      reperfusion suggesting that changes in their expressions could occur at gene or
      mRNA levels. ERM protein expression and distribution were unaffected by ischemia
      reperfusion. Together, these data show that renal ischemia-reperfusion induced
      expression and redistribution of actin and microtubule cytoskeleton components in
      addition to Rho GTPases in proximal tubules, suggesting that they participate in
      an adaptive response to cellular lesions.

PMID- 15464725
TI  - Identification of the region required for the antiapoptotic function of the
      cyclin kinase inhibitor, p21.
AB  - The CDK inhibitor, p21, exhibits an antiapoptotic or proapoptotic effect, in
      addition to its anti-proliferative effect, depending on the conditions. To define
      the apoptosis-regulatory function of p21, we constructed cells that stably
      express C-terminal deletion mutants of p21 (full length 164aa), 1-157, 1-147 or 1
      128, and evaluated the apoptotic response of these cells. The AnnexinV positive
      cell fraction after gamma-irradiation did not increase in cells expressing 1-157.
      Consistently, an increase of caspase3 activity or the active form of caspase3 was
      not observed in cells expressing 1-157, but was prominent in cells expressing 1
      128 and 1-147. Further, the activity of caspase9 was suppressed in gamma
      irradiated cells expressing 1-157. The antiapoptotic effect of 1-157 was weaker
      in Fas-induced apoptosis. Our data indicate that the 1-157 region of p21 inhibits
      apoptosis caused by gamma-irradiation by reducing the activity of caspase9 and
      caspase3, and the 148-157 region is critical for its inhibiting activity.

PMID- 15464726
TI  - Human myeloperoxidase catalyzes an oscillating peroxidase-oxidase reaction.
AB  - We have studied the peroxidase-oxidase reaction catalyzed by human
      myeloperoxidase in an open system where both substrates-molecular oxygen and NADH
      are supplied continuously to the reaction mixture. The reaction shows oscillatory
      kinetics at pH values around 5, provided that the reaction medium in addition to
      the enzyme and the substrates also contains an aromatic electron mediator such as
      melatonin or 4-hydroxybenzoic acid and chloride ions at concentrations >1mM. The
      experimental findings can be simulated by a detailed model of the reaction. The
      results are important for our understanding of oxidant production in neutrophils.

PMID- 15464727
TI  - Heterologous expression and biophysical characterization of soluble
      oligosaccharyl transferase subunits.
AB  - Oligosaccharyl transferase (OT) catalyzes the first committed step in N-linked
      protein glycosylation, a co-translational process that occurs in the lumen of the
      endoplasmic reticulum. The yeast Saccharomyces cerevisiae enzyme complex
      comprises nine integral membrane proteins, five of which are essential for
      catalysis. Due to the challenges with purifying the active enzyme complex for
      detailed biophysical studies, a systematic study to express, isolate, and
      characterize the soluble domains of three of the largest subunits in the complex
      (Nlt1p, Wbp1p, and Swp1p) is reported. The proteins are expressed using the lytic
      baculovirus expression system and the new constructs are well behaved, monomeric
      in solution, and glycosylated. Two of the proteins interact with each other as
      seen by gel filtration and circular dichroism. This study provides a framework to
      study the roles of these three essential subunits of the eukaryotic OT complex.

PMID- 15464729
TI  - Structural roles of the active site iron(III) ions in catechol 1,2-dioxygenases
      and differential secondary structure changes in isoenzymes A and B from
      Acinetobacter radioresistens S13.
AB  - The reversible active site metal ion removal process for two catechol 1,2
      dioxygenase isoenzymes (IsoA and IsoB) isolated from Acinetobacter radioresistens
      S13 has been monitored using circular dichroism and fluorescence spectroscopic
      techniques. IsoA and IsoB are homodimers, containing one iron(III) ion per
      subunit. Their amino acid sequence identity is 48.4%. Previous experiments
      suggested that structural diversities could be responsible for the differential
      thermal and pH stabilities of the two isoenzymes and of their distinct
      demetallation kinetics. The far-UV CD spectra of IsoA and IsoB catechol 1,2
      dioxygenases from A. radioresistens S13 provide information on their secondary
      structures. IsoB appears to have a content of alpha-helices higher than IsoA.
      Upon metal ion removal, both proteins reversibly lose part of their secondary
      structure following distinct pathways. CD spectra simulations allowed us to
      estimate the content of alpha-helices, beta-sheets, and turns for each isoenzyme
      and to monitor the secondary structure rearrangements. The metal ion withdrawal
      has large influence on the secondary structure: in particular a significant
      reduction of alpha-helices content is observed for both isoenzymes. Intrinsic
      fluorescence emission spectra clearly support such results, adding information on
      the local environment changes of the tryptophan residues. The positioning of
      Trp250 in IsoB has been shown to be of particular interest for monitoring the
      local structure changes occurring upon metal ion removal. For the first time
      these studies allow to underline the role of active site iron ions on
      dioxygenases folding and stability, further evidencing the differences in
      structural assembling between the two isoenzymes from A. radioresistens S13.

PMID- 15464728
TI  - Requirement of c-jun transcription factor on the mouse mast cell protease-6
      expression in the mast cells.
AB  - Mast cell tryptases may be a key mediator in mast cell-mediated inflammatory
      reactions, and these expressions can be regulated by microenvironmental factors
      of tissues, particularly stem cell factor. In the present study, we investigated
      whether the transcription of mouse mast cell protease-6 (mMCP-6) gene was caused
      by SCF-mediated c-jun. We observed that mMCP-6 mRNA was expressed by
      overexpression of c-jun in the immature mast cell line in which both mMCP-6 and c
      kit receptor are negative. The c-jun increased synergistically the luciferase
      activity of mMCP-6 promoter through the direct interaction with mi transcription
      factor (MITF). The synergic effect of c-jun with MITF was abolished by deletion
      of sequence between nt -171 and -151 in the mMCP-6 promoter. Furthermore, the
      level of mMCP-6 mRNA in mast cells was attenuated by the introduction of dominant
      negative c-jun (TAM-67) and the treatment of Jun N-terminal kinase inhibitor,
      SP600125. These results show that c-jun might play a role in regulating the
      transcription of mMCP-6 gene in mast cells stimulated by SCF.

PMID- 15464730
TI  - ATP, histidine or magnesium ions can protect DNA against sisomicin-induced
      damage, following stray Cu(II) binding.
AB  - The oxidative DNA damage by the cupric complexes of sisomicin was investigated in
      the presence of varying amounts of histidine, ATP, Mg(II) ions or phosphates. We
      found that by very low concentrations, the amino acid is able to inhibit the
      cleavage totally. This occurs both by its competition with antibiotic for
      copper(II) binding, what was proved by spectroscopic measurements, as well as by
      ROS scavenging by the imidazole ring. ATP and magnesium also exert an influence
      on the yield of the DNA destruction by decreasing the amount of the single strand
      breaks, however only their significant excess is able to break this process. The
      influence of ATP on the plasmid damage has in this case a similar chemical
      mechanism to that one observed for histidine. Mg(II) ions, however, interact with
      DNA and thus prevent the complex binding. Only phosphate anions, in the range of
      their physiological concentrations, exert no influence on the cleavage process.

PMID- 15464731
TI  - E2F1 regulation of the human myo-inositol 1-phosphate synthase (ISYNA1) gene
      promoter.
AB  - Human myo-inositol 1-phosphate synthase (IP synthase; E.C. 5.5.1.4), encoded by
      ISYNA1, catalyzes the de novo synthesis of inositol 1-phosphate from glucose 6
      phosphate. It is a potential target for mood-stabilizing drugs such as lithium
      and valproate. But, very little is known about the regulation of human IP
      synthase. Here, we have characterized the minimal promoter of ISYNA1 and show
      that it is upregulated by E2F1. Upregulation occurs in a dose-dependent fashion
      and can be suppressed by ectopic expression of Rb. EMSA and antibody supershift
      analysis identified a functional E2F binding motif at -117. Complex formation at
      this site was competed by an excess of unlabeled Sp1 oligo consistent with the 
      117 E2F site overlapping an Sp1 motif. Because the -117 E2F motif is not a high
      affinity binding site, we propose that the upregulation of ISYNA1 occurs through
      the cooperative interaction of several low-affinity E2F binding motifs present in
      the minimal promoter.

PMID- 15464732
TI  - Aromatic hydroxamic acids and hydrazides as inhibitors of the peroxidase activity
      of prostaglandin H2 synthase-2.
AB  - The cyclooxygenase activity of the bifunctional enzyme prostaglandin H(2)
      synthase-2 (PGHS-2) is the target of non-steroidal anti-inflammatory drugs.
      Inhibition of the peroxidase activity of PGHS has been less studied. Using Soret
      absorption changes, the binding of aromatic hydroxamic acids to the peroxidase
      site of PGHS-2 was examined to investigate the structural determinants of
      inhibition. Typical of mammalian peroxidases, the K(d) for benzhydroxamic acid
      (42mM) is much greater than that for salicylhydroxamic acid (475microM). Binding
      of the hydroxamic acid tepoxalin (25microM) resulted in only minor Soret changes.
      However, tepoxalin is an efficient reducing cosubstrate, indicating that it is an
      alternative electron donor rather than an inhibitor of the peroxidase activity.
      Aromatic hydrazides are metabolically activated inhibitors of peroxidases. 2
      Naphthoichydrazide (2-NZH) caused the time- and concentration-dependent
      inhibition of both PGHS-2 peroxidase and cyclooxygenase activities. H(2)O(2) was
      required for the inactivation of both PGHS-2 activities and indomethacin (which
      binds at the cyclooxygenase site) did not affect the peroxidase inhibitory
      potency of 2-NZH. A series of aromatic hydrazides were found to be potent
      inhibitors of PGHS-2 peroxidase activity with IC(50) values in the 6-100microM
      range for 13 of the 18 hydrazides examined. Selective inhibition of PGHS-2 over
      myeloperoxidase and horseradish peroxidase isozyme C was increased by certain
      ring substitutions. In particular, a chloro group para to the hydrazide moiety
      increased the PGHS-2 selectivity relative to both myeloperoxidase and horseradish
      peroxidase isozyme C.

PMID- 15464733
TI  - Perchlorate-induced conformational transition of Staphylococcal nuclease:
      evidence for an equilibrium unfolding intermediate.
AB  - The sodium perchlorate-induced conformational transition of Staphylococcal
      nuclease has been monitored by both circular dichroism (CD) and fluorescence
      spectroscopy. The perchlorate-induced transition is cooperative as observed by
      both spectroscopic signals. However, the protein loses only about one-third of
      its native far-UV CD signal at high perchlorate concentrations, indicating that a
      significant amount of secondary structure remains in the post-transition state.
      The remaining CD signal can be further diminished in a cooperative manner by the
      addition of the strong denaturant, urea. Near-UV CD spectra clearly show that the
      protein loses its tertiary structure in the perchlorate-induced denatured state.
      The perchlorate-induced transition curves were fit to the standard two-state
      model and the standard free energy change and m value of the transition are
      2.3kcal/mol and 1.8kcal/(molM), respectively. By comparison, the urea-induced
      unfolding of Staphylococcal nuclease (in the absence of perchlorate) yields an
      unfolding free energy change, DeltaG(0,un), of 5.6kcal/mol and an m value of
      2.3kcal/(molM). Thus, the thermodynamic state obtained in the post-transition
      region of perchlorate-induced conformation transition has a significantly lower
      free energy change, a high content of secondary structure, and diminished
      tertiary structure. These results suggest that the perchlorate-induced denatured
      state is a partially folded equilibrium state. Whether this intermediate is
      relevant to the folding/unfolding path under standard conditions is unknown at
      this time.

PMID- 15464734
TI  - Evidence for the involvement of cAMP-GEF (Epac) pathway in amylase release from
      the rat parotid gland.
AB  - Amylase release from the rat parotid gland is mainly mediated in a cAMP-dependent
      protein kinase (PKA)-dependent manner. In the present study, amylase release
      mediated in cAMP-dependent and PKA-independent manners was investigated with a
      cAMP-regulated guanine nucleotide exchange factor (cAMP-GEF: Epac)-selective cAMP
      analogue, 8CPT-2Me-cAMP. The Epac was localized in the intracellular and the
      plasma membrane fractions. PKA activation by 8CPT-2Me-cAMP was 100-fold lower
      than that by cAMP. The amylase release (% of the total) from the intact parotid
      acinar cells was 16 and 3.6% by isoproterenol (1microM) and 8CPT-2Me-cAMP
      (200microM), respectively, and that from the saponin-permeabilized cells was 15
      and 3% by cAMP (100microM) and 8CTP-2Me-cAMP (10microM), respectively. H-89
      inhibited cAMP-induced amylase release, but did not inhibit 8CPT-2Me-cAMP-induced
      amylase release. These results indicated that amylase release by beta-adrenergic
      stimulation is mediated through both the cAMP/PKA and cAMP/Epac signal pathways.

PMID- 15464735
TI  - Inactivation of neutrophil NADPH oxidase upon dilution and its prevention by
      cross-link and fusion of phox proteins.
AB  - Activation of the phagocyte NADPH oxidase involves assembly of p47(phox),
      p67(phox), Rac, and flavocytochrome b(558), and the activation can be triggered
      in a cell-free system with an anionic amphiphile. We find that the activated
      oxidase in a pure cell-free system was rapidly inactivated upon dilution. When
      the activated oxidase was treated with a chemical cross-linker, 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide, the half-life of the oxidase in dilution was
      extended from 1min to 4h at 25 degrees C. The cross-linked oxidase was resistant
      to inhibition by inactive flavin analogs, indicating that cross-linking prevents
      flavin exchange. When a fusion protein p67N-p47N plus RacQ61L was added,
      flavocytochrome b(558) became spontaneously active. Cross-linking of this mixture
      produced an oxidase that was extremely stable to dilution (t(1/2)=6.6h). Western
      blotting analysis showed the presence of a cross-link between p67N-p47N and
      RacQ61L. These results suggest that covalently linked phox components prevents
      FAD loss and stabilizes the longevity of the stoichiometric complex, extending
      the lifespan of the active oxidase.

PMID- 15464736
TI  - Detection of hydrogen peroxide with Amplex Red: interference by NADH and reduced
      glutathione auto-oxidation.
AB  - We report here that reduced pyridine nucleotides and reduced glutathione result
      in an oxidation of Amplex Red by dioxygen that is dependent on the presence of
      horseradish peroxidase (HRP). Concentrations of NADH and glutathione typically
      found in biological systems result in the oxidation of Amplex Red at a rate
      comparable to that produced, for example, by respiring mitochondria. The effects
      of NADH and glutathione in this assay system are likely to be the result of
      H(2)O(2) generation via a superoxide intermediate because both catalase and
      superoxide dismutase prevent the oxidation of Amplex Red. These results suggest
      caution in the assay of H(2)O(2) production in biological systems using the
      Amplex Red/HRP because the assay will also report the mobilization of NADH or
      glutathione. However, the interruption of this process by the addition of
      superoxide dismutase offers a simple and reliable method for establishing the
      source of the oxidant signal.

PMID- 15464737
TI  - Protein proteinase inhibitor genes in combat against insects, pests, and
      pathogens: natural and engineered phytoprotection.
AB  - The continual need to increase food production necessitates the development and
      application of novel biotechnologies to enable the provision of improved crop
      varieties in a timely and cost-effective way. A milestone in this field was the
      introduction of Bacillus thuringiensis (Bt) entomotoxic proteins into plants.
      Despite the success of this technology, there is need for development of
      alternative strategies of phytoprotection. Biotechnology offers sustainable
      solutions to the problem of pests, pathogens, and plant parasitic nematodes in
      the form of other insecticidal protein genes. A variety of genes, besides (Bt)
      toxins that are now available for genetic engineering for pest resistance are
      genes for vegetative insecticidal proteins, proteinase inhibitors, alpha-amylase
      inhibitors, and plant lectins. This review presents a comprehensive summary of
      research efforts that focus on the potential use and advantages of using
      proteinase inhibitor genes to engineer insect- and pest-resistance. Crop
      protection by means of PI genes is an important component of Integrated Pest
      Management programmes.

PMID- 15464738
TI  - Quantitative autoradiography of adenosine receptors and NBTI-sensitive adenosine
      transporters in the brains of mice deficient in the preproenkephalin gene.
AB  - There is a large body of evidence indicating important interactions between the
      adenosine and the opioid systems in regulating pain, opioid dependence and
      withdrawal. Mice lacking the proenkephalin gene and therefore lacking the
      endogenous enkephalin peptides have been successfully developed and exhibit
      decreased locomotor activity, are hyperalgesic and show enhanced anxiety and
      aggression. In addition, an upregulation of mu and delta receptors was also
      observed in the brains of knockout mice. To investigate if there are any
      compensatory alterations in adenosine systems in the brains of mutant mice, we
      have carried out quantitative autoradiographic mapping of A(1) and A(2A)
      adenosine receptors and nitrobenzylthioinosine (NBTI)-sensitive adenosine
      transporters in the brains of wild-type and homozygous enkephalin knockout mice.
      Adjacent coronal brain sections were cut from brains of +/+ and -/- mice for the
      determination of binding of [(3)H]1,3-dipropyl-8-cyclopentylxanthine
      ([(3)H]DPCPX), [(3)H]2-[p-(2-carbonylethyl)phenylethylamino]-5'-N
      ethylcarboxamidoadenosine ([(3)H]CGS21680) or [(3)H]NBTI to A(1) and A(2A)
      adenosine receptors and NBTI-sensitive adenosine transporters, respectively. A
      small but significant increase in [(3)H]DPCPX and [(3)H]NBTI binding but no
      significant change in [(3)H]CGS21680 binding was detected in enkephalin knockout
      brains. The results provide further evidence of functional interactions in the
      brain between opioid receptors and A(1) adenosine receptors as well as NBTI
      sensitive adenosine transporters but not A(2A) receptors.

PMID- 15464739
TI  - Acute social defeat reduces neurotrophin expression in brain cortical and
      subcortical areas in mice.
AB  - Acute social defeat in mice activates the hypothalamic-pituitary-adrenal axis
      (HPA) and induces long-term behavioral changes, including exaggerated fear
      responses and inhibition of territorial behavior. Stress-induced hormonal and
      neurotransmitter release may contribute to disruption of expression of genes
      important for cell survival, neuronal plasticity, and neuronal remodeling. Brain
      derived neurotrophic factor (BDNF) is a neurotrophic factor associated with
      structural cellular changes that occur during nervous system development and
      contributes to neural plasticity in the adult brain. In rats, acute (1-2 h)
      restraint stress transiently reduces BDNF mRNA expression in the hippocampus, a
      region important in the memory and in HPA regulation; restraint stress also
      decreases BDNF expression in the basolateral amygdala (BLA), a region important
      for fear consolidation and emotional memory. We hypothesized that a brief (10
      min) exposure to intense social stress, a more naturalistic stressor than
      restraint stress, would also reduce BDNF mRNA in the hippocampus and BLA of mice.
      In the present study, we examined the time course of expression of BDNF mRNA
      expression in the hippocampus and amygdala, as well as other subcortical and
      cortical brain regions, following acute social stress. In situ hybridization
      analysis for BDNF mRNA expression showed that there was a significant decrease in
      BDNF mRNA expression in all regions studied in mice 24 h after social defeat when
      compared to control (naive) mice (P<0.05). These findings support our hypothesis
      that BDNF mRNA levels are reduced by social stress, and may have implications for
      brain plasticity and behavioral changes following social stress.

PMID- 15464740
TI  - Effects of repeated injections of the neurotensin analog NT69L on dopamine
      release and uptake in rat striatum in vitro.
AB  - The effect of five daily intraperitoneal (i.p.) injections of NT69L on in vitro
      dopamine release, uptake, and [(3)H]NT binding in rat striatal tissue was
      investigated. NT69L perfusion increased K(+)-evoked and electrically evoked
      [(3)H]DA release. NT receptor-1 antagonist SR48692 inhibited the stimulatory
      effect of NT69L on K+-evoked [(3)H]DA release, but not on electrical
      depolarization. Pretreatment with NT69L, in vivo, daily for 5 days, did not cause
      significant change in K(+) evoked [(3)H]DA release, but reduced electrically
      evoked [(3)H]DA release induced by NT69L perfusion. Repeated perfusion with NT69L
      in vitro caused marked reduction on K(+)-evoked [(3)H]DA release and no change in
      electrically evoked [(3)H]DA release. [(3)H]NT binding was not significantly
      changed by one injection but was decreased after five injections of NT69L.
      Desensitization to the effects of NT69L in vitro was different depending upon
      whether tissue was preexposed to the compound in vivo or in vitro. These results
      provide further proof for the involvement of different NT receptor subtypes in
      mediating the effect of NT69L on dopamine release evoked by K(+) or electrical
      depolarization.

PMID- 15464741
TI  - EPR evidence of hydroxyl radical generation as an initiator of lipid peroxidation
      in amyloid beta-protein-stimulated PC12 cells.
AB  - Recent data from several groups suggest that the primary mechanism of amyloid
      beta-protein (Abeta) neurotoxicity may be mediated by free radicals. To evaluate
      this hypothesis, our aim is to make the mechanism of Abeta neurotoxicity clear,
      especially in the formation of free radicals. In this study, rat pheochromocytoma
      (PC12) cells were exposed to Abeta25-35 and confirmed free radical generations
      using two kinds of spin trap agents, 5,5-dimethyl-1-pyrroline-N-oxide; DMPO and
      alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; POBN. DMPO spin adduct revealed
      that hydroxyl radical (OH), while POBN spin adduct identified a lipid radical (L)
      as electron paramagnetic resonance (EPR) evidence of lipid peroxidation in the
      process of cell damage by Abeta25-35 exposure. An Abeta cytotoxicity assay also
      was performed by using WST-8 reduction system and histochemical analysis. These
      analyses showed cell damage induced by Abeta. This study provides EPR evidence
      that Abeta neurotoxicity is derived from hydrogen abstraction from
      polyunsaturated lipid acid by hydroxyl radical as a cause of lipid peroxidation.

PMID- 15464742
TI  - Crush injury induces NMDA-receptor-dependent delayed nerve cell death in rat
      entorhinal-hippocampal slice cultures.
AB  - The aim of the present study was to develop an in vitro model that produces an
      injury-induced delayed nerve cell death. We used entorhinal-hippocampal slices
      from 12-day-old rats, which were cultured for 14 days before experiments prior to
      a crush injury in the middle layers of the entorhinal cortex. Crush injury
      increased specific propidium iodide (PI) fluorescence at the site of primary
      injury at day 1. Specific PI fluorescence decreased over the following days, with
      a slower decrease taking place at days 4-7. At days 4-7, PI fluorescence
      increased in CA1 and CA3. Treatment with 30 microM MK-801 for 2 h at the time of
      crush injury prevented the increase in PI fluorescence at days 4-7 at the site of
      injury, in CA1, and in CA3. Crush injury induced TUNEL-positive cells at the site
      of injury at days 1 and 5. MK-801 markedly reduced the number of TUNEL-positive
      cells observed at day 5, but had no effect on the number of TUNEL-positive cells
      at day 1. The present data indicate that crush injury may induce two types of
      secondary cell death. The first, early, type of cell death is induced quickly and
      is maximal at day 1, after which the dead cells are gradually removed. The
      second, delayed, type of cell death appears at day 4. NMDA receptor antagonism
      prevents the induction of the delayed cell death but has no effect on the early
      cell death.

PMID- 15464743
TI  - Peripheral oxidative biomarkers constitute a valuable indicator of the severity
      of oxidative brain damage in acute cerebral infarction.
AB  - Oxidative stress contributes to post-ischemic brain damage. We assessed the
      correlation between plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a marker of
      oxidative DNA damage, and progressive brain damage in rats subjected to transient
      or permanent ischemia. Male Wistar rats were subjected to permanent- and 0.5-, 1
      , 2-h middle cerebral artery occlusion (MCAO). At various times thereafter, the
      infarct volume, 8-OHdG levels in plasma and brain tissue, DNA fragmentation, and
      immunohistochemical observations on their brains were recorded and compared. At
      12 h after 2-h MCAO-reperfusion, the cortical infarct volume was increased; it
      peaked at 24 h. DNA degeneration expanded from the caudate putamen into the
      cortical region at 12 h. 8-OHdG-containing cells in the cortical infarct zone
      were observed at 12 h, the number of 8-OHdG-positive cells was highest at 24 h
      and they co-localized with DNA single-strand breaks. Plasma 8-OHdG significantly
      increased at 12 h, and peaked at 24 h after reperfusion (1.1+/-0.7 ng/ml (mean+/
      S.D.); controls 0.3+/-0.1; p<0.01). This increase was in step with increased
      infarct volume, DNA degradation, and reflected immunohistochemical findings in
      the cortical region but not the caudate putamen. In the permanent MCAO model,
      plasma 8-OHdG levels were associated with the brain contents of 8-OHdG. Plasma 8
      OHdG and the cortical infarct volume were lower in the 0.5- and 1-h than the 2-h
      MCAO model. Our findings suggest that 8-OHdG as a peripheral biomarker may be an
      indicator of oxidative brain damage in acute cerebral infarction.

PMID- 15464744
TI  - Disinhibition of maternal behavior following neurotoxic lesions of the
      hypothalamus in primigravid rats.
AB  - Virgin female rats do not respond maternally to foster pups due to an endogenous
      neural circuit that actively inhibits the display of maternal behavior. Once
      pregnant, primigravid rats will continue to avoid foster pups until just prior to
      or at parturition. Anosmia or lesions of the olfactory tract, medial amygdala,
      and areas of the hypothalamus will stimulate virgin females to display maternal
      behavior rapidly, but little is known of the effect of these lesions in
      primigravid rats. The objective of the present study was to determine if
      neurotoxic lesions of the dorsomedial (DMH) and ventromedial nuclei (VMH) of the
      hypothalamus will advance the onset of maternal behavior in primigravid rats.
      Nulliparous Sprague-Dawley female rats were mated and then on day 8 of gestation
      bilaterally infused with N-methyl-d-aspartic acid (NMDA; 8 microg/0.2
      microl/side) or vehicle directed toward either the DMH or VMH. Beginning on day
      15 of gestation until parturition, females were tested daily for maternal
      responsiveness. DMH and VMH lesions significantly advanced the onset of maternal
      behavior (5-6 days vs. 0-1 day before parturition) in first-time pregnant rats.
      These results indicate that the DMH and VMH are involved in the regulation of
      maternal behavior and may be part of an endogenous neural circuit that inhibits
      maternal behavior during pregnancy.

PMID- 15464745
TI  - Distinct patterns of Fos expression induced by systemic amphetamine in the
      striatal complex of C57BL/6JICo and DBA/2JICo inbred strains of mice.
AB  - Mice from the inbred strains C57BL/6 and DBA/2 are characterized by striking
      differences in their behavioral response to addictive drugs. We used Fos
      expression as a tool to reveal strain differences in the postsynaptic effects of
      amphetamine (AMPH; 2.5 mg/kg) within the nucleus accumbens (NAc) (core and shell)
      and the dorsal caudate (dorsomedial and dorsolateral). AMPH stimulated Fos
      expression in all striatal regions of mice from both strains. However, while
      C57BL/6 showed a higher Fos response than DBA/2 mice in both NAc shell and core,
      the opposite was true for the dorsolateral caudate. The effects of AMPH were
      prevented by D1 blockade in all striatal regions of both strains and mimicked by
      the D1 agonist, SKF82958 (0.1 mg/kg), in both regions of the caudate and in the
      NAc shell, but not in the core. Our results suggest that the functional
      heterogeneity of the striatal complex is under genetic control and that this
      control may implicate DA transmission and corticostriatal interactions.

PMID- 15464746
TI  - Role of nociceptin in the modulation of nociception in the arcuate nucleus of
      rats.
AB  - Neuropeptide nociceptin/orphanin FQ is the endogenous ligand for the opioid
      receptor-like receptor 1 (ORL1), mediating essential functions in the central and
      peripheral nervous systems. The present study was performed to investigate the
      role of nociceptin and ORL1 receptor in nociception and morphine-induced
      antinociception in the arcuate nucleus of hypothalamus in rats. Hindpaw
      withdrawal latencies (HWL) were measured by hot-plate and Randall Selitto tests.
      The HWL to both thermal and mechanical stimulation decreased significantly after
      intra-arcuate nucleus injection of nociceptin in a dose-dependent manner. The
      effect of nociceptin was blocked significantly by subsequent intra-arcuate
      nucleus administration of [Nphe(1)]nociceptin(1-13)-NH(2), an ORL1 receptor
      antagonist. Furthermore, an intra-arcuate nucleus injection of nociceptin
      dramatically attenuated the antinociceptive effect induced by morphine either
      injected in the same site or applied intraperitoneally. These results suggest
      that nociceptin in the arcuate nucleus induces a hyperalgesic effect by acting on
      ORL1 receptors. The present study also demonstrates an interaction between
      nociceptin and opioids in the arcuate nucleus of the hypothalamus.

PMID- 15464747
TI  - Regional brain cholecystokinin changes as a function of friendly and aggressive
      social interactions in rats.
AB  - Cholecystokinin (CCK) is the most abundant neuropeptide in the mammalian brain,
      and has been implicated in the regulation of a diversity of emotions and
      motivations including negative affect and stress responses. In this experiment,
      we assayed levels of CCK (CCK4/5 and CCK8) from tissue homogenates in intruder
      animals 6 h after resident-intruder inter-male aggression. Intruder animals that
      demonstrated submissive behavior (freezing and 22-kHz ultrasonic vocalizations)
      had higher levels of CCK in the tegmentum and posterior cortex as compared to non
      submissive (i.e., "Friendly") intruder animals. Ultrasonic vocalizations (22-kHz)
      were positively correlated with CCK levels in the tegmentum, posterior cortex and
      pituitary. These data suggest that CCK may play a role in the generation of
      negative affective states indexed by 22-kHz ultrasonic calls in certain regions
      of the brain.

PMID- 15464748
TI  - Influence of season and environment on adult neurogenesis in the central
      olfactory pathway of the shore crab, Carcinus maenas.
AB  - In most vertebrates hitherto examined including humans, certain brain areas
      retain the capacity to build new neurons during adult life. In some arthropods,
      above all in crustaceans, continuous genesis of brain neurons has also been
      shown, namely for soma clusters of the olfactory brain. Several factors as, e.g.,
      sensory input, living conditions, or stress, are known to influence the rate of
      cell proliferation, survival, and cell differentiation. The present study was
      undertaken to test whether seasonal changes and/or captivity would influence the
      proliferation of cells in the lateral cluster (LC) of the olfactory lobe (OL) and
      in the cluster of the hemiellipsoid body (HB) of the eyestalk of shore crabs.
      During a period of more than a year, 5-bromo-deoxyuridine (BrdU) injections were
      administered to freshly caught animals and to animals kept for 12 weeks after
      capture under artificial conditions. Counts of BrdU-labeled cells showed that
      animal size, seasonal changes as well as captivity had an influence on the number
      of proliferating cells. Further, in the lateral soma cluster and the soma cluster
      of the hemiellipsoid body, cell proliferation is most likely regulated
      independently. While the lateral soma cluster showed two peaks of cell
      proliferation (spring and late summer), the soma cluster of the hemiellipsoid
      body had only one peak in early summer. Furthermore, proliferation decreased with
      size and hence age of the animal only in the lateral soma cluster but not in the
      soma cluster of the hemiellipsoid body. Although captivity reduced the number of
      newborn cells in general, cell proliferation remained synchronous with the
      seasons of the year, indicating that an endogenous circannual rhythm regulates
      neurogenesis.

PMID- 15464749
TI  - Binding of two potential imaging agents targeting amyloid plaques in postmortem
      brain tissues of patients with Alzheimer's disease.
AB  - In vivo imaging of amyloid plaques may be useful for evaluation and diagnosis of
      Alzheimer's disease (AD) patients. Towards that end, we have developed 6-iodo-2
      (4'-dimethylamino-)phenyl-imidazo[1,2]pyridine (IMPY), and 4-N-methylamino-4'
      hydroxystilbene (SB-13) as ligands for specifically targeting amyloid plaques.
      These ligands can be readily radiolabeled with I-123 or C-11, for in vivo imaging
      using single photon emission computerized tomography (SPECT) or positron emission
      tomography (PET), respectively. However, in order to be useful in vivo, probes
      must show selective high affinity binding to a sufficiently abundant binding site
      on amyloid plaques. Therefore, as a prelude to in vivo imaging studies, we
      evaluated the binding properties of these two potential imaging agents to amyloid
      plaques present in human brain tissues. In vitro binding studies were carried out
      with [(125)I]IMPY and [(3)H]SB-13 in homogenates prepared from postmortem samples
      of affected cortex and cerebellum of pathologically confirmed AD patients and age
      matched controls. Binding parameters such as K(d) and B(max) were estimated.
      Competition study was designed to evaluate the amyloid plaque binding specificity
      using human brain tissues. Plaque binding was confirmed by thioflavin-S staining.
      Specific [(125)I]IMPY or [(3)H]SB-13 binding can be clearly measured in the
      cortical gray matter, but not in the white matter of AD cases. There was a very
      low specific binding in cortical tissue homogenates of control brains. Cerebellar
      homogenates prepared from either AD or control brains did not show any specific
      [(125)I]IMPY or [(3)H]SB-13 binding. The K(d) values of AD cortical homogenates
      were 5.3+/-1.0 and 2.4+/-0.2 nM for [(125)I]IMPY and [(3)H]SB-13, respectively.
      High binding capacity and comparable values were observed for both ligands (14-45
      pmol/mg protein). The location and density of specific signal detected by
      [(125)I]IMPY or [(3)H]SB-13 correlated with the distribution of amyloid plaques
      in these brain specimens, as confirmed by thioflavin-S staining. Competition
      profiles of known ligands suggest that the binding is highly selective and
      comparable to that reported by using preformed Abeta peptide aggregates.
      [(125)I]IMPY and [(3)H]SB-13 show an abundant binding capacity with high binding
      affinities for amyloid plaques in affected cortical regions of AD brains. These
      properties suggest that when labeled with I-123 or C-11, these two ligands may be
      useful to quantitate amyloid plaque burdens in the living AD patients.

PMID- 15464750
TI  - Cardiovascular responses to microinjection of L-glutamate into the NTS in AV3V
      lesioned rats.
AB  - The excitatory amino acid L-glutamate injected into the nucleus of the solitary
      tract (NTS) in unanesthetized rats similar to peripheral chemoreceptor activation
      increases mean arterial pressure (MAP) and reduces heart rate. In this study, we
      investigated the effects of acute (1 day) and chronic (15 days) electrolytic
      lesions of the preoptic-periventricular tissue surrounding the anteroventral
      third ventricle (AV3V region) on the pressor and bradycardic responses induced by
      injections of L-glutamate into the NTS or peripheral chemoreceptor activation in
      unanesthetized rats. Male Holtzman rats with sham or electrolytic AV3V lesions
      and a stainless steel cannula implanted into the NTS were used. Differently from
      the pressor responses (28+/-3 mm Hg) produced by injections into the NTS of sham
      lesioned rats, L-glutamate (5 nmol/100 nl) injected into the NTS reduced MAP (
      26+/-8 mm Hg) or produced no effect (2+/-7 mm Hg) in acute and chronic AV3V
      lesioned rats, respectively. The bradycardia to l-glutamate into the NTS and the
      cardiovascular responses to chemoreflex activation with intravenous potassium
      cyanide or to baroreflex activation with intravenous phenylephrine or sodium
      nitroprusside were not modified by AV3V lesions. The results show that the
      integrity of the AV3V region is essential for the pressor responses to L
      glutamate into the NTS but not for the pressor responses to chemoreflex
      activation, suggesting dissociation between the central mechanisms involved in
      these responses.

PMID- 15464751
TI  - Age-related changes in growth hormone (GH)-releasing hormone and somatostatin
      neurons in the hypothalamus and in GH cells in the anterior pituitary of female
      mice.
AB  - We have observed growth hormone-releasing hormone (GHRH)-immunoreactive (ir)
      neurons in the arcuate nucleus (ARC), somatostatin (SS)-ir neurons in the
      periventricular nucleus (PeN), and pituitary growth hormone (GH)-ir cells in
      female C57BL/6J mice at 2 months old (2 M), 4, 12 and 23 M, using
      immunocytochemical and morphometric methods. The number of GHRH-ir neurons
      decreased with age. The number of SS-ir neurons increased from 2 to 4 M, but
      decreased after 4 M. The volume of the anterior pituitary and the number of
      adenohypophysial parenchymal cells fell from 12 to 23 M. The proportion of GH-ir
      cells decreased significantly from 2 to 4 M and decreased in number from 12 to 23
      M as well as in size from 2 to 4 M and from 12 to 23 M. Our results show that
      both GHRH-ir neurons and SS-ir neurons are fewer in old female mice, but the
      ratio of the number of SS-ir neurons to GHRH-ir neurons increases in old females.
      We suggest that the fall in the number and size of GH-ir cells in the pituitary
      gland with age may be involved in the increase in the ratio of the number of SS
      ir neurons to GHRH-ir neurons in the hypothalamus in female mice, as well as in
      males.

PMID- 15464752
TI  - Interactions of allosteric modulators of AMPA/kainate receptors on spreading
      depression in the chicken retina.
AB  - The functional role of AMPA and kainate receptors in spreading depression (SD)
      was investigated in the isolated chicken retina. Competitive (NBQX) and non
      competitive (GYKI 52466, GYKI 53405 and GYKI 53655) antagonists of the AMPA
      receptor inhibited AMPA-induced SD in a concentration-dependent manner.
      Concentrations of drugs caused 50% inhibition (IC(50) values) are 0.2, 16.6, 7.0
      and 1.4 microM, respectively. AMPA receptor positive modulator cyclothiazide was
      more effective in the potentiation of SD evoked by AMPA than by kainate. Slight
      potentiation of either AMPA- or kainate-induced SD was observed only at high
      concentration (1 mg/ml) by the kainate receptor modulator concanavalin A.
      Compounds that positively modulate AMPA receptor function (cyclothiazide, IDRA
      21, S 18986, 1-BCP and aniracetam) caused a concentration-dependent potentiation
      in SD. Concentrations of drugs that caused 50% potentiation (estimated EC(50)
      values) are 9, 135, 142, 450 and 1383 microM, respectively. Interaction between
      cyclothiazide, aniracetam or S 18986 administered with each other, or with GYKI
      52466, respectively, was also investigated. When cyclothiazide and S 18986 were
      co-applied, their effects seemed to be additive. However, lack of additivity was
      obtained when S 18986 was added together with aniracetam. Positive modulators
      applied at equiactive concentrations reduced the inhibitory action of GYKI 52466
      and differently shifted its concentration-response curve. In this respect, S
      18986 was the most effective (IC(50) of GYKI 52466 changed from 16.6 to 51.9
      microM). Our findings indicate the contribution of AMPA rather than kainate
      receptors in the mediation of retinal spreading depression. Our data further
      support the idea that multiple positive modulatory sites are present on the AMPA
      receptor complex in addition to a negative modulatory site.

PMID- 15464753
TI  - The size of the whisker barrel field in adult rats: minimal nondirectional
      asymmetry and limited modifiability by chronic changes of the sensory input.
AB  - We have evaluated quantitatively the whisker barrel field (posteromedial barrel
      subfield, PMBSF) size in rats raised in standard cages and in rats chronically
      exposed to an enriched sensory environment. Some animals were subjected to either
      chronic trimming of the right whiskers, or permanent transection of the right
      infraorbital nerve. Coronal brain sections were Nissl-stained or reacted for
      cytochrome oxidase. All, except the IoN-transected rats, showed +/-5% variation
      in mean PMBSF thickness, with no consistent side bias. In the transected animals,
      however, the left PMBSF was a significant 3.1% shallower than the right. This
      denervation-dependent radial shrinkage was consistent with an 11% volume
      shrinkage of the deafferented PMBSF. The mean volume of the PMBSF ranged between
      8.7 and 9.5 mm(3), with moderate interindividual variability (3.5% to 11%). No
      significant differences in PMBSF volume were found between groups in the right
      hemisphere, nor in the right vs. left ratios. However, the PMBSF volume was a
      significant 6.6% larger in the enriched animals without whisker trimming. The
      PMBSF volume correlated positively with neocortical volume, and with PMBSF cortex
      thickness, in rats exposed to enriched environment. These data show that: (1)
      there is a moderate interanimal and lateral variability in the PMBSF volume, with
      no side preference; (2) exposing young adult rats to an enriched environment
      induces a discrete but significant enlargement of the PMBSF; (3) the effects of
      whisker trimming on the contralateral PMBSF, if any, are lost in the interanimal
      and lateral variability; and (4) such changes reach significance, however, when
      studied in combination with exposure to an enriched environment.

PMID- 15464754
TI  - The pattern of brain c-fos mRNA induced by a component of fox odor, 2,5-dihydro
      2,4,5-trimethylthiazoline (TMT), in rats, suggests both systemic and processive
      stress characteristics.
AB  - Predators to rodents and their associated odors are increasingly chosen to study
      the neural mechanisms of stress and anxiety. Specifically, predatory odors are
      believed to elicit responses based on the perceived threat (psychological or
      processive), rather than to any direct systemic effects (pain, blood loss,
      infection, etc.) of the stimulus, which are mediated by distinct neural pathways.
      The hypothesis that a chemical component from fox feces, 2,5-dihydro-2,4,5
      trimethylthiazoline (TMT), elicits stress responses by specific activation of
      processive neural pathways was tested. Different amounts of TMT (range: 0-600
      micromol) or the control odor butyric acid (0-1200 micromol) were presented to
      male Sprague-Dawley rats for 30 min. Immediately after odor presentation, rats
      were sacrificed, blood levels of adrenocorticotropic hormone (ACTH) and
      corticosterone were measured, and brains were rapidly harvested to measure
      regional brain c-fos mRNA induction by in situ hybridization. Presentation of TMT
      (> or =75 micromol), but not butyric acid (up to 1200 micromol), significantly
      increased ACTH and corticosterone release. TMT presentation, especially with
      amounts (> or =75 micromol) producing endocrine activation, induced c-fos mRNA in
      several brain areas, including the olfactory bulb, lateral septal nucleus,
      septohypothalamic nucleus, anteromedial and oval nuclei of the bed nucleus of the
      stria terminalis, the central nucleus of the amygdala, the anteroventral,
      anterodorsal, and medial preoptic nuclei, the anterior, dorsomedial, lateral,
      supramammillary, dorsal premammillary and paraventricular hypothalamic nuclei,
      the external lateral parabrachial nucleus, the locus coeruleus, and the nucleus
      of the solitary tract. Interestingly, these brain regions represent a mix of
      regional c-fos mRNA induction pattern not reported previously with any other
      single stressor. These results suggest that TMT elicits stress responses through
      a relatively unique and complex mix of brain regions associated with both
      processive and systemic neural pathways, unlike those seen in response to cat
      odors.

PMID- 15464755
TI  - Galanin over-expression decreases the development of neuropathic pain-like
      behaviors in mice after partial sciatic nerve injury.
AB  - The neuropeptide galanin may have a role in modulation of nociception,
      particularly after peripheral nerve injury. Here we assessed the development of
      neuropathic pain-like behaviors in mice overexpressing galanin under the dopamine
      beta-hydroxylase promoter. Unoperated galanin over-expressing mice exhibited a
      moderately reduced sensitivity to noxious heat. Both galanin over-expressing mice
      and wild-type controls developed mechanical and heat hypersensitivity after
      photochemically induced partial sciatic nerve ischemic injury. The magnitude and
      persistence of such pain-like behaviors were significantly less, and recovery was
      faster in galanin over-expressing mice compared to wild types. However, the
      recovery from toe-spread deficits did not differ between galanin over-expressing
      and wild-type mice after a crush injury to the sciatic nerve. Thus, early
      recovery in pain-like response is unlikely to result from accelerated
      regeneration in the galanin over-expressing mice. Immunohistochemical analysis
      showed that galanin is over-expressed both in small and large dorsal root
      ganglion cells in the transgene mouse, whereas large galanin-positive neurons
      were never seen in wild-type mice. The present results in general support an
      inhibitory role of galanin in nociception and indicate that increased
      availability of galanin in spinal dorsal horn at the time or shortly after nerve
      injury may reduce the development of pain-like behaviors in mice.

PMID- 15464756
TI  - Serotonergic neurons of the caudal raphe nuclei activated in response to
      hemorrhage in the rat.
AB  - The response to a sudden, severe loss of blood volume is complex and results in a
      drastic fall in arterial blood pressure and sympathoinhibition. The present study
      examines the distribution of serotonergic neurons in the caudal raphe involved in
      the mediation of the response to severe hemorrhage. Hemorrhage was performed in
      rats anesthetised with urethane by withdrawal of blood at a rate of 1 ml/min for
      approximately 4 min until blood pressure fell to 50 mm Hg. Sections through the
      brainstem were processed immunohistochemically to identify Fos, the protein
      product of the proto-oncogene c-fos expressed in the nucleus of neurons activated
      during the hemorrhage stimulus, and double-labeled to identify serotonin (5
      hydroxytryptamine; 5-HT) content of cells. In response to hemorrhage, double
      labeled Fos/5-HT neurons were located in the B3 region which includes the raphe
      magnus (RM) and its lateral extension. Hemorrhage-induced Fos-positive neurons
      that were not serotonergic were located in raphe pallidus (RP), parapyramidal
      cell group (PP), and the B3 region. Serotonergic neurons not activated by
      hemorrhage were located in the nucleus raphe pallidus, the parapyramidal cell
      group, the raphe obscurus (RO), and the B3 region. The specific rostrocaudal
      distribution of activated neurons may indicate different functions of groups of
      neurons in the response to hemorrhage.

PMID- 15464757
TI  - Nociceptive stimuli induce changes in somatosensory responses of rat dorsal
      column nuclei neurons.
AB  - Accumulating evidence suggest that the dorsal column nuclei (DCN) neurons play a
      role in nociception. To evaluate DCN neuronal responses to nociceptive stimuli,
      unit recordings were performed in urethane-anesthesized rats. Neurons selected
      for this analysis displayed a low spontaneous firing rate and some of them were
      antidromically activated by electrical stimulation of the ventral posterolateral
      thalamic nucleus. Formalin injections into receptive fields (RFs) of DCN cells,
      or applications of short-lasting and long-lasting thermal nociceptive stimuli
      were used. DCN neurons displayed smaller responses when long-lasting nociceptive
      thermal stimuli were applied to their RFs in comparison with values obtained from
      the innocuous cutaneous stimulation (5.2+/-1.0 and 4.0+/-0.6 spikes/stimuli,
      respectively; p=0.02). Formalin also decreased the responses to innocuous
      cutaneous stimuli when these stimuli were applied to the formalin injection site
      (2.6+/-0.3 spikes/stimuli in control conditions and 1.8+/-0.3 spikes/stimuli 20
      min after formalin; p=0.002). In contrast, responses to sensory stimuli applied
      at the periphery of the RF after formalin injection increased (2.2+/-0.2 to 2.8+/
      0.3 spikes/stimuli; p=0.005). In some cases, DCN neurons expanded their RF. Fiber
      input to the DCN did not modify their somatosensory responses when nociceptive
      stimuli were applied. Results demonstrate that thermal and formalin nociceptive
      stimuli modify the somatosensory responses of DCN neurons. Thus, decreasing
      somatosensory responses at the pain induction site or the generation of allodynia
      may be due to the activity of DCN neurons.

PMID- 15464758
TI  - Functional correlates of somatostatin receptor 2 overexpression in the retina of
      mice with genetic deletion of somatostatin receptor 1.
AB  - Somatostatin-14 (SRIF) and its receptors (sst(1-5)) are found in the mammalian
      retina. However, scarce information is available on the role of the
      somatostatinergic system in retinal physiology. We have recently used gene
      knockout technology to gain insights into the function of sst(1) and sst(2)
      receptors in the mouse retina. The sst(1) receptor localizes to SRIF-containing
      amacrine cells, whereas the sst(2) receptor localizes to several retinal cell
      populations including rod bipolar cells (RBCs). Molecular data indicate that, in
      retinas with deletion of the sst(1) receptor (sst(1) KO), sst(2) receptors become
      overexpressed in concomitance with an increased level of retinal SRIF. To test
      whether this up-regulation of sst(2) receptors correlates with altered sst(2)
      receptor physiology, we studied the effect of sst(2) receptor activation on
      potassium current (I(K)) in isolated RBCs and glutamate release in retina
      explants. Both I(K) and glutamate release are known to be negatively modulated by
      sst(2) receptors in the mammalian retina. We used octreotide, a SRIF analogue, to
      activate selectively sst(2) receptors. Patch-clamp recordings from isolated RBCs
      indicated that the sst(2) receptor-mediated inhibition of I(K) was significantly
      larger in sst(1) KO than in control retinas. In addition, HPLC measurements of
      glutamate release in sst(1) KO retinal explants demonstrated that the sst(2)
      receptor-mediated inhibition of K(+)-evoked glutamate release was also
      significantly larger than in control retinas. As a whole, these findings indicate
      that the overexpression of sst(2) receptors in sst(1) KO retinas can be
      correlated to an enhanced function of sst(2) receptors. The level of expression
      of sst(2) receptors may therefore represent a key step in the regulation of
      sst(2) receptor-mediated responses, at least in the retina.

PMID- 15464759
TI  - Microglial reactivity to beta-amyloid is modulated by astrocytes and
      proinflammatory factors.
AB  - The brains of Alzheimer's disease (AD) patients present activated glial cells,
      amyloid plaques and dystrophic neurites. The core of amyloid plaques is composed
      of aggregated amyloid peptide (Abeta), a peptide known to activate glial cells
      and to have neurotoxic effects. We evaluated the capability of glial cells to
      mediate Abeta(1-42) cytotoxicity in hippocampal cultures. Conditioned media
      obtained from microglial cultures exposed to Abeta induced apoptosis of
      hippocampal cells. This pro-apoptotic effect was not observed in hippocampal
      cultures exposed to conditioned media obtained from mixed glial (astrocytes and
      microglia) cultures that had been exposed to Abeta. Microglia exposed to Abeta
      responded with reactive morphological changes, induction of iNOS, elevated nitric
      oxide production and decreased reductive metabolism. All these responses were
      attenuated by the presence of astrocytes. This astrocyte modulation was however,
      not observed when glial cells were exposed to proinflammatory factors
      (LPS+Interferon-gamma) alone or in combination with Abeta. Our results suggest
      that astrocytes and proinflammatory molecules are determining factors in the
      response of microglia to Abeta.

PMID- 15464760
TI  - Post-stress changes in BDNF and Bcl-2 immunoreactivities in hippocampal neurons:
      effect of chronic administration of olanzapine.
AB  - In the present study, we used a repeated restraint stress animal model to observe
      the changes in the expression of brain-derived neurotrophic factor (BDNF) and B
      cell lymphoma protein-2 (Bcl-2) in hippocampal neurons of rats, monitored the
      time course of the expression over 3 weeks post-stress period, and examined the
      effects of the chronic administration of olanzapine on the time course.
      Olanzapine is an atypical antipsychotic drug that has been shown to be
      neuroprotective in previous in vitro studies. We found: (1) the repeated
      restraint stress decreases the levels of expression of BDNF and Bcl-2 in
      hippocampal neurons; (2) the stress-induced decreases spontaneously recover to
      their pre-stress levels in 3 weeks after the last stress exposure; (3)
      administration of olanzapine for 1 week returns the expression of Bcl-2 to its
      pre-stress level, and the administration for 3 weeks causes an excessive
      expression of BDNF in hippocampal neurons. In the context of the lower levels of
      BDNF and Bcl-2, and structural brain abnormalities observed in patients with
      schizophrenia, our findings suggest that BDNF and Bcl-2 may be involved in the
      pathophysiology of schizophrenia and in the therapeutic action of atypical
      antipsychotic drugs.

PMID- 15464761
TI  - Amygdala-kindling does not induce a persistent loss of GABA neurons in the
      substantia nigra pars reticulata of rats.
AB  - GABAergic inhibition of the substantia nigra pars reticulata (SNR) has been shown
      to suppress seizures in most models of epilepsy, including the amygdala-kindling
      model of temporal lobe epilepsy (TLE). A dysfunction of this seizure gating
      mechanism of the SNR may lead to facilitation of seizure propagation in such
      models. In post-status epilepticus models of TLE, GABAergic neurons in the SNR
      are damaged, but it is not known whether such damage also occurs in kindling. By
      using stereological techniques for cell counting in amygdala-kindled rats, we
      determined the density of SNR neurons that were labeled for GABA by
      immunohistochemistry or for the two isoforms of the GABA-synthesizing enzyme
      glutamate decarboxylase (GAD), GAD65 and GAD67, by in situ hybridization (ISH).
      In addition, GABA neurons in the basolateral amygdala (BLA) were counted. While
      there was a significant reduction of GAD65 mRNA expressing neurons in the BLA of
      kindled rats, no alteration in the density of neurons was observed in the
      anterior or posterior SNR when cells were counted 6 weeks after the last kindled
      seizure. Our previous finding of reduced GAD and GABA levels in synaptosomes
      isolated from the SN of kindled rats together with the present observation of
      unchanged density of SNR neurons in such rats suggest that kindling affects the
      GABAergic projections from the striatum or globus pallidus to the SNR rather than
      directly affecting GABA neurons in the SNR.

PMID- 15464762
TI  - Immunocytochemical localization of TNF type 1 and type 2 receptors in the rat
      spinal cord.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is secreted in numerous
      pathophysiological situations by a variety of cell types. Tactile
      hypersensitivity (allodynia) is one component of a constellation of "illness
      behaviors" triggered by TNF-alpha. TNF-alpha is also implicated in neuropathic
      pain after peripheral nerve injury and apoptosis after spinal cord injury (SCI).
      It is possible that SCI, illness- and peripheral injury-induced hypersensitivity
      may share a similar spinal mediated etiology. These studies identify the locus of
      type-1 TNF (TNFR1 or p55) and type-2 TNF (TNFR2 or p75) receptors within the
      spinal cord. At all spinal levels, TNFR1 receptor immunoreactivity (TNFR1-ir) was
      constitutively expressed on cells and afferent fibers within the dorsal root
      ganglia, afferent fibers of the dorsal root, dorsal root entry zone (REZ) and
      within lamina I and II of the dorsal horn. Unilateral dorsal rhizotomy eliminated
      the characteristic pattern of TNFR1-ir at the rhizotomized REZ. In contrast,
      TNFR2-ir was consistently absent from dorsal root fibers and the region of the
      root entry zone. Consistent with our previous report, medullary afferent fibers
      in the solitary tract and spinal trigeminal tract labelled for TNF1-ir, but did
      not express TNFR2-ir. The presence TNFR1-ir on dorsal horn afferents, suggests
      that TNF-alpha may be a mechanism responsible for tactile hypersensitivity during
      illness. The presence of TNFR1 receptors, and perhaps their long-term activation
      or plasticity, may also play a critical role in the chronic allodynia and
      hyperreflexia observed after SCI or peripheral nerve damage.

PMID- 15464763
TI  - Increased c-fos-like immunoreactivity in the superior colliculus and lateral
      geniculate nucleus of the rd mouse.
AB  - In most subcortical visual centers in normal mice maintained for a period in the
      dark, very few neurons express fos-like immunoreactivity (FLI), most likely
      reflecting c-fos expression, but if an animal is exposed to a flashing light,
      there is transient increase in the number of FLI-expressing cells. In dark
      maintained retinal degeneration (rd) mice, with an inherited photoreceptor
      defect, numbers of FLI-positive cells, identified immunohistochemically, are
      anomalously elevated in the superior colliculus (SC) and lateral geniculate
      nucleus (LGN). Eye removal largely prevents the elevated counts. The difference
      in number of FLI-positive cells in the SC of rd mice and nondystrophic controls
      is highly significant (p<0.001). Because we have previously found a similar
      phenomenon in Royal College of Surgeons (RCS) rats, in which photoreceptor loss
      is caused by a retinal pigment cell defect, it argues for an effect related to
      photoreceptor loss rather than its cause.

PMID- 15464764
TI  - Age-related susceptibility to oxygen and glucose deprivation damage in rat
      hippocampal slices.
AB  - Aging is an important risk factor for stroke. We evaluated the effects of aging
      on cell susceptibility to oxygen and glucose deprivation (OGD) in slices of the
      hippocampus from Wistar rats aged 2, 11 and 24 months. Lactate dehydrogenase
      (LDH) released to the incubation media and free radical content were markedly
      increased in the 24-month group submitted to OGD. These results confirm that
      hippocampal tissue from old animals is more susceptible to ischemia-reoxygenation
      injury.

PMID- 15464765
TI  - Presumptive FMRF-amide-like immunoreactive retinopetal fibres in Crocodylus
      niloticus.
AB  - A small contingent of 30-50 of centrifugal visual fibres, showing FMRF-amide-like
      immunoreactivity, has been identified in C. niloticus; these fibres extend from
      the chiasmatic region into the retina. They do not take the marginal optic tract,
      but pass medially to the chiasmatic fascicles, from the preoptic region. The
      cells of origin of these fibres have not been identified. However, none of the
      retinopetal neurons of the brainstem [M. Medina, J. Reperant, R. Ward, D. Miceli,
      Centrifugal visual system of Crocodylus niloticus : a hodological, histochemical
      and immunocytochemical study, J. Comp. Neurol. 468 (2004) 65-85], labelled by
      retrograde transport of rhodamine beta-isothiocyanate after intraocular injection
      of this tracer, show FMRF-amide-like immunoreactivity; neither are any of the
      FMRF-amide-like immunopositive neurons in the crocodile brain, particularly those
      of the complex involving the terminal nerve and the septo-preoptic region,
      labelled by rhodamine after its intraocular injection.

PMID- 15464766
TI  - Hypersensitivity to pentylenetetrazol-induced convulsion in mice lacking the PLC
      related inactive protein-1.
AB  - In the present study, we investigated the effects of pentylenetetrazol (PTZ), a
      chemical convulsant that interacts with the GABA(A) receptor, in mice lacking the
      phospholipase C (PLC)-related inactive protein-1 (PRIP-1). PRIP-1 knockout mice
      did not develop spontaneous behavioral seizure. PRIP-1 knockout mice had markedly
      shorter latencies until the first clonic convulsion (CL) and tonic extensor (TE)
      following PTZ administration and increased incidence of convulsion compared to
      those in wild-type mice. Furthermore, the mortality rate by PTZ in mice lacking
      the PRIP-1 was also significantly increased in comparison with that in wild-type
      mice. These findings suggested that mice lacking the PRIP-1 were hypersensitive
      to PTZ-induced convulsion, and PRIP-1 might play roles in suppressing excessive
      excitability via interactions with the GABA(A) receptor.

PMID- 15464767
TI  - Sublingual misoprostol versus methylergometrine for active management of the
      third stage of labor.
AB  - OBJECTIVE: To compare the efficacy and side effects of sublingual misoprostol and
      intravenous methylergometrine for active management of third stage of labor.
      METHOD: One hundred twenty low risk pregnant women at term with spontaneous onset
      of labor were included in the study. The women were randomized to receive either
      two tablets of misoprostol (200 microg/tablet) sublingually or 1 ml of
      methylergometrine (200 microg) intravenous injection, after the delivery of the
      anterior shoulder of the baby. The main outcome measures were: need for
      additional oxytocic drugs, blood loss >or=500 ml, change in hemoglobin levels and
      side effects. RESULTS: Postpartum hemorrhage as defined by hemorrhage >or=500 ml
      occurred in 3.1% of the women in the sublingual misoprostol group but none of the
      women in the methylergometrine group (P > 0.05). There was a need for additional
      oxytocic drugs in 5.0% and 8.3% after methylergometrine and misoprostol,
      respectively (P > 0.05). The change in hemoglobin levels at 24 h postpartum were
      0.8 and 0.7 gm% in methylergometrine and misoprostol group, respectively(P >
      0.05). In the misoprostol group, 6.6% women developed fever >or=38 degrees C and
      21.6% had shivering while in methylergometrine group none experienced these side
      effects. However, the incidence of other side effects like nausea, vomiting,
      headache and giddiness were similar in both groups. CONCLUSION: Sublingual
      misoprostol appears to be as effective as intravenous methylergometrine in the
      prevention of postpartum hemorrhage. However, larger randomized studies are
      needed to advocate its routine use.

PMID- 15464768
TI  - High and low dose oxytocin in augmentation of labor.
AB  - OBJECTIVE: To compare the efficacy and safety of high dose oxytocin in the
      augmentation of labor. METHOD: Two hundred pregnant women requiring augmentation
      of labor were randomly assigned to receive oxytocin by either a low dose protocol
      (1.5 microm/min initially, increased by 1.5 microm/min every 30 min) or a high
      dose protocol (4.5 microm/min initially, increased by 4.5 microm/min every 30
      min). RESULTS: High dose of oxytocin was associated with a significant shortening
      of labor 4 (1.10-10) vs. 6 (1-10) h, p<0.0001 without a significant difference in
      cesarean delivery rate, neonatal and maternal outcome. CONCLUSION: The use of
      high dose oxytocin is associated with significantly shorter labor without any
      adverse fetal and maternal effects.

PMID- 15464769
TI  - Mode of delivery after one cesarean section.
AB  - OBJECTIVES: To investigate labor patterns and mode of delivery of aginal births
      after cesarean (VBAC) versus unsuccessful trial of labor after cesarean (TOLAC)
      in a South African district hospital, and the influence of the indication for the
      primary cesarean section (C-section) on the subsequent mode of delivery. METHODS:
      Retrospective audit of the partogram of 202 VBAC and 382 repeat C-section. There
      were 108 elective repeat cesarean deliveries (ERCD) and 274 emergency repeat C
      sections after unsuccessful TOLAC. The indication of the primary C-section was
      known in 127: 43 (33.9%) VBAC and 84 (66.1%) repeat C-sections. RESULTS: The
      indication for the primary C-section in terms of recurrent/non-recurrent did not
      affect the subsequent mode of delivery (chi(2)=3.5; P=0.06; OR 0.49, 95% CI 0.23
      1.04). The indication of the primary C-section in terms of dysfunctional/non
      dysfunctional labor did not reoccur in the same parturients (chi(2)=0.01; P=0.91;
      OR 0.94, 95% CI 0.35-2.55). CONCLUSION: Dysfunctional labor accounted for most
      primary and repeat emergency C-sections, but not as a recurrent condition in the
      same parturients.

PMID- 15464770
TI  - Acute effects of maternal smoking on fetal hemodynamics.
AB  - OBJECTIVE: To investigate acute effects of cigarette smoking on fetal
      hemodynamics. METHOD: Sixty seven women between 32nd to 40th weeks of gestation
      were evaluated. Maternal blood pressure and heart rate, fetal heart rate (FHR)
      tracing, umbilical and fetal middle cerebral arterial (MCA) color Doppler
      measurements were evaluated. Pre- and postsmoking results were compared with
      paired t-test. RESULTS: Maternal heart rate significantly increased after
      smoking. Baseline FHR and FHR variability remained unchanged. The number of
      participants who had a reactive NST was 60 in 67 before smoking (89.5%) and
      decreased to 47 after smoking (70.1%) (p=0.009). There were no significant
      changes between maximum and minimum flow velocities, pulsatility index (PI),
      resistance index (RI) and systolic/diastolic flow ratio (S/D) of umbilical and
      middle cerebral arteries. CONCLUSION: The nicotine load of a single cigarette may
      be inadequate to cause a detectable decrease in utero-placental blood flow;
      however, smoking prior to the FHR recording may alter the FHR reactivity.

PMID- 15464771
TI  - A comparison of abdominal and vaginal hysterectomy for the large uterus.
AB  - OBJECTIVE: To compare the perioperative outcomes of women with an enlarged uterus
      (>or=250 g) who had abdominal and vaginal hysterectomies. METHOD: Retrospective
      study of the perioperative outcomes of 288 consecutive women with an enlarged
      uterus, of whom 200 underwent an abdominal hysterectomy and 88 a vaginal
      hysterectomy, all for benign gynecological conditions. RESULTS: Among the
      perioperative complications, only the risk of ileus was significantly higher in
      the group that underwent abdominal hysterectomy. Although the need for blood
      transfusions was similar between the groups, mean perioperative hemoglobin change
      was significantly lower for women who had the abdominal approach. Vaginal
      hysterectomy shortened the length of hospitalization significantly but did not
      affect the operative time. All of these differences remained significant after
      adjusting for uterine weight (P<0.05). Baseline characteristics were similar
      between the groups, except for uterine weight. CONCLUSIONS: For women with a
      uterus weighing 250 g or more, vaginal hysterectomy shortens the hospital stay
      without significantly increasing perioperative morbidity when compared with the
      abdominal route.

PMID- 15464772
TI  - Gonadotrophin dynamics during reproductive life.
AB  - OBJECTIVE: To evaluate the follicle-stimulating hormone (FSH) and luteinizing
      hormone (LH) levels in early follicular phase throughout the reproductive years.
      METHOD: FSH and LH concentrations were determined by radioimmunoassay (RIA).
      Linear and polynomial regressions were carried out considering basal FSH as the
      dependent and age as the independent variable. RESULTS: FSH levels increased
      throughout the reproductive years (P<0.025). A positive correlation between age
      and basal FSH levels was detected (P<0.05). The Pearson squared coefficient of
      r(2)=0.889 was obtained. Using polynomial regression, the inclination of the
      parabole (Y=7.97-0.009x+0.057x(2)) was 0.359 and the generalized correlation
      coefficient was r=0.795. The goodness of fit analysis showed that the parabole
      may better represent the phenomenon (F=4.7; P<0.05). The LH levels remained
      constant, increasing only beyond 40 years of age. CONCLUSION: The FSH levels rose
      in a nonlinear way during the reproductive life and the LH concentrations
      increased discreetly only in patients over 40 years of age.

PMID- 15464773
TI  - Finasteride versus cyproterone acetate-estrogen regimens in the treatment of
      hirsutism.
AB  - OBJECTIVES: To compare the clinical and hormonal effects of finasteride and a
      combination regimen of cyproterone acetate (CPA) plus ethinyl estradiol (EE2) in
      the treatment of hirsutism. METHODS: Forty hirsute women were enrolled in a
      prospective randomized trial. Twenty-nine had polycystic ovary syndrome (PCOS)
      and 11 had idiopathic hirsutism. Patients were randomly treated with finasteride
      (5 mg/day; n=20) or CPA plus EE2 [CPA (25 mg/day on days 5-14) plus EE2 (20
      microg/day on days 5-25) n=20] for 9 months. Main outcome measurement was a
      reduction in hair growth. Hirsutism score and hormone levels were measured at the
      beginning and at the end of the study. The student t-test and Mann-Whitney U
      tests were used for analysis of the data. RESULTS: The modified Ferriman-Gallwey
      scores for hirsutism decreased significantly at the end of the study from a
      mean+/-SD of 23.7+/-4.4 to 11.3+/-1.5; P=<0.001 in finasteride group and from
      22.3+/-4.2 to 11.4+/-1.2; P=<0.001 in CPA plus EE2 group. Improvement of
      hirsutism induced by the two treatment methods was similar (47.6 % vs. 51.1%;
      P=0.2). Treatment with CPA plus EE2 significantly decreased serum total and free
      T, A, DHEAS, and DHT and increased SHBG levels. Finasteride significantly
      increased total T but reduced DHT levels. CONCLUSION: Finasteride and CPA plus
      EE2 are equally effective in decreasing hirsutism, despite significantly
      different effects on serum hormone levels.

PMID- 15464774
TI  - Urethral avulsion injury during vacuum extraction delivery.

PMID- 15464775
TI  - Pre-pregnancy weight, low pregnancy weight gain, and preterm delivery.

PMID- 15464776
TI  - Last menstrual period versus ultrasound for pregnancy dating.

PMID- 15464777
TI  - Dinoprostone intracervical gel for cervical ripening.

PMID- 15464778
TI  - Rupture in an unscarred uterus during second trimester pregnancy termination with
      mifepristone and misoprostol.

PMID- 15464779
TI  - Lack of effectiveness of CO2 cryotherapy for treatment of CIN.

PMID- 15464780
TI  - Vaginal anterior colposuspension (VACS) for cystocele.

PMID- 15464781
TI  - Secondary occupational amenorrhea.

PMID- 15464782
TI  - Massive ascites secondary to ovarian schistosomiasis.

PMID- 15464783
TI  - Effects of finasteride on the morphology of polycystic ovaries.

PMID- 15464785
TI  - Pakistani obstetricians' recognition of and attitude towards domestic violence
      screening.
AB  - OBJECTIVE: Our study assesses Pakistani obstetricians knowledge of the prevalence
      of domestic violence in clinical practice and attitudes towards instituting
      screening protocols during routine antenatal care. METHODS: One hundred
      obstetricians, all Karachi residents, were randomly drawn from a stratified
      sampling list taken from membership lists. A structured questionnaire assessing
      prevalence, attitudes, and beliefs on training and domestic violence screening
      protocols was administered. RESULTS: Nearly 70% of obstetricians reported that
      more than 30% of Pakistani women are victims of domestic abuse. Sixty-two
      obstetricians specified that they had identified a physically abused woman within
      the past year. Almost half of the respondents were favorably inclined to screen
      patients. Professional, personal and patient-related barriers were identified as
      the main hurdles preventing instituting screening. CONCLUSIONS: The desire for
      instituting routine screening despite the recognition of major hurdles by
      Pakistani obstetricians should propel reproductive health stakeholders to raise
      awareness about appropriately modifying standard antenatal care protocols.

PMID- 15464784
TI  - Management of the third stage of labor in an Egyptian teaching hospital.
AB  - OBJECTIVES: The study describes normal labor practices in an Egyptian teaching
      hospital for the first time, where postpartum hemorrhage is the leading cause of
      maternal mortality. Third-stage management patterns are described and compared to
      evidence-based medicine. Reasons for third-stage practices observed are explored.
      STUDY DESIGN: 176 normal births were directly observed. Women were interviewed
      postpartum and study findings were shared with providers. RESULTS: Third-stage
      active management was correctly done for 15% of women observed. Most common
      deviations for the remaining 85% were: giving uterotonic drugs after placental
      delivery (65%) and without cord traction (49%). Passive management was not done
      for any observed delivery. CONCLUSIONS: The preventive role actively managing the
      third stage can provide against postpartum hemorrhage was lost to the majority of
      the deliveries observed. Obstacles to adopting protocols shown to reduce
      hemorrhage should be explored, given the contribution of postpartum hemorrhage to
      maternal deaths in Egypt.

PMID- 15464786
TI  - The Diabetes and Pre-eclampsia Intervention Trial.
AB  - OBJECTIVE: Rates of pre-eclampsia in women with type 1 diabetes are two to four
      times higher than in normal pregnancies. Diabetes is associated with antioxidant
      depletion and increased free radical production, and an increasing body of
      evidence suggests that oxidative stress and endothelial cell activation may be
      relevant to disease pathogenesis in pre-eclampsia. The Diabetes and Pre-eclampsia
      Intervention Trial (DAPIT) aims to establish if pregnant women with type 1
      diabetes supplemented with vitamins C and E have lower rates of pre-eclampsia and
      endothelial activation compared with placebo treatment. METHODS: DAPIT is a
      randomised multicentre double-blind placebo-controlled trial that will recruit
      756 pregnant women with type 1 diabetes from 20 metabolic-antenatal clinics in
      the UK over 4 years. Women are randomised to daily vitamin C (1000 mg) and
      vitamin E (400 IU) or placebo at 8-22 weeks of gestation until delivery. Maternal
      venous blood is obtained at randomisation, 26 and 34 weeks, for markers of
      endothelial activation and oxidative stress and to assess glycaemic control. The
      primary outcome of DAPIT is pre-eclampsia. Secondary outcomes include endothelial
      activation (PAI-1/PAI-2) and birthweight centile.

PMID- 15464787
TI  - Obstetric fistula: the challenge to human rights.
AB  - Obstetric fistula can be explained to result from different causes. These holes
      in the tissue wall between the vagina and bladder and/or rectum are most
      prevalent in resource-poor countries, attributable to prolonged obstructed labour
      and absent or inaccessible remedial prenatal services. Obstructed labour is often
      due to small pelvic size, resulting from women's youth and premature childbearing
      and/or malnutrition. Poverty at national health-service and family levels often
      predisposes pregnant populations to suffer high rates of fistula. Global
      estimates showing up to 100,000 new cases each year and 2 million affected girls
      and women are probably gross underestimates. Fistula devastates lives of
      sufferers, who are often expelled by husbands and become isolated from their
      families and communities. Failures of states to provide prenatal preventive care
      (including medically indicated cesarean deliveries) and timely fistula repair
      violate women's internationally recognized human rights, especially to healthcare
      in general and reproductive healthcare in particular.

PMID- 15464788
TI  - Editor's comment.

PMID- 15464789
TI  - FIGO Save the Mothers Initiative: the Pakistan-UK collaboration.
AB  - The pilot study in Punjab, Pakistan was one of the five paired demonstration
      projects sponsored by FIGO in the "Save the Mothers" maternal mortality project.
      The goal of the project was to bring basic and comprehensive emergency obstetric
      care (EmOC) to a semiurban and rural area some 30 km from Lahore, where
      effectively there was none. The aim was to achieve this by using the existing
      facilities within the rural health system without the deployment of extra
      specialist staff other than as initial facilitators. This report shows trebling
      of some performance indicators and an improvement in met need. There is
      coincidentally a similar increase in the uptake of general medical services.
      Reducing maternal mortality requires building local capacity for EmOC; the
      essential components being the premises, trained personnel, equipment, and
      availability of drugs and blood. Availability and provision of EmOC coupled with
      changes in the attitude of the population resulted in marked improvement of
      process indicators.

PMID- 15464790
TI  - Managing equipment for emergency obstetric care in rural hospitals.
AB  - In resource-poor countries, substantial sums of money from governments and
      international donors are used to purchase equipment for health facilities. WHO
      estimates that 50-80% of such equipment remains non-functional. This article is
      based on experience from various projects in developing countries in Asia and
      Africa. The key issues in the purchase, distribution, installation, management
      and maintenance of equipment for emergency obstetric care (EmOC) services are
      identified and discussed. Some positive examples are described to show how common
      equipment management problems are solved.

PMID- 15464791
TI  - Complicated deliveries, critical care and quality in emergency obstetric care in
      Northern Tanzania.
AB  - Our objective was to determine the availability and quality of obstetric care to
      improve resource allocation in northern Tanzania. We surveyed all facilities
      providing delivery services (n=129) in six districts in northern Tanzania using
      the UN Guidelines for monitoring emergency obstetric care (EmOC). The three last
      questions in this audit outline are examined: Are the right women (those with
      obstetric complications) using emergency obstetric care facilities (Met Need)?
      Are sufficient quantities of critical services being provided (cesarean section
      rate (CSR))? Is the quality of the services adequate (case fatality rate (CFR))?
      Complications are calculated using Plan 3 of the UN Guidelines to assess the
      value of routine data for EmOC indicator monitoring. Nearly 60% of the expected
      complicated deliveries in the study population were conducted at EmOC qualified
      health facilities. 81.2% of the expected complicated deliveries are conducted in
      any facility (including facilities not qualifying as EmOC facilities). There is
      an inadequate level of critical services provided (CSR 4.6). Voluntary agencies
      provide most of these services in rural settings. All indicators show large
      variations with the setting (urban/rural location, level and ownership of
      facilities). Finally, there is large variation in the CFR with only one facility
      meeting the minimum accepted level. Utilization and quality of critical obstetric
      services at lower levels and in rural districts must be improved. The potential
      for improving the resource allocation within lower levels of the health care
      system is discussed. Given the small number of qualified facilities yet
      relatively high Met Need, we argue that it is neither the mothers' ignorance nor
      their lack of ability to get to a facility that is the main barrier to receiving
      quality care when needed, but rather the lack of quality care at the facility.
      Little can be concluded using the CFR to describe the quality of services
      provided.

PMID- 15464792
TI  - Use of the BET adsorption isotherm equation to examine styrene adsolubilization
      by nonionic surfactants at the water-silica interface.
AB  - A modified BET adsorption isotherm equation was used to explain adsolubilization
      at the water-silica interface, producing a method for understanding
      adsolubilization that is independent of admicelle structure. The two constants k1
      and k2 provide a measure of the surfactant-solute and solute-solute interactions,
      respectively. As predicted, k1 changed with various factors including surfactant
      structure, the presence and quantity of added lipophilic linker and hexane. On
      the other hand, k2 was fairly constant for all examined systems having the same
      solute. Commonly used partition coefficients can be easily related to the model
      and adsolubilization isotherms may be reproduced by the developed equation.
      Inferences about solute distribution at the interface and its location within the
      admicelle may be extracted from the results. The model is useful in explaining
      trends in adsolubilization and in predicting adsolubilization behavior for
      similar systems.

PMID- 15464793
TI  - Effects of carboxyl groups on the adsorption behavior of low-molecular-weight
      substances on a stainless steel surface.
AB  - The adsorption isotherms of various carboxylic acids and several amines on a
      stainless steel surface were taken as a function of pH and the ionic strength of
      the solution at 30 degrees C. In particular, the effect of the number of carboxyl
      groups on the adsorption behavior was investigated. Monocarboxylic acids such as
      benzoic acid and n-butyric acid were reversibly adsorbed on the stainless steel
      particles and showed a Langmuir-type adsorption isotherm, i.e., Q=KqmC/(1+KC),
      where Q and C are, respectively, the amount of adsorbate adsorbed and the
      equilibrium concentration in the bulk solution, qm, the maximum adsorbed amount,
      and K is the adsorption equilibrium constant. Carboxylic acids having plural
      carboxyl groups had much higher affinity to the surface and were adsorbed in both
      reversible and irreversible modes. The adsorption isotherms for the carboxylic
      acids having plural carboxyl groups could be expressed by a modified Langmuir
      type adsorption isotherm, i.e., Q=q(irrev)+Kq(rev)C/(1+KC), where q(irrev) and
      q(rev) are, respectively, the maximum amounts adsorbed irreversibly and
      reversibly. The K and q(irrev) values increased with an increase in the number of
      carboxyl groups except for isophthalic acid and terephthalic acid. On the basis
      of the pH dependencies of K, qm, q(irrev), and q(rev) as well as the surface
      properties of the stainless steel, both reversible and irreversible adsorptions
      were considered to occur through the electrostatic interaction between negatively
      charged carboxyl groups and the positively charged sites on the surface. The
      dependency of the q(irrev) value on ionic strength was discussed on the basis of
      the differences in their adsorbed state with the interaction forces to the
      surface and repulsive forces among the adsorbed molecules. The adsorption of
      amine components was quite weak. The RA-IR and molecular dynamics calculation
      were done to investigate the adsorption states of phthalic acid, trimellitic
      acid, and mellitic acid.

PMID- 15464794
TI  - Kinetics and equilibrium adsorption study of lead(II) onto activated carbon
      prepared from coconut shell.
AB  - Removal of lead from aqueous solutions by adsorption onto coconut-shell carbon
      was investigated. Batch adsorption experiments were performed to find out the
      effective lead removal at different metal ion concentrations. Adsorption of Pb2+
      ion was strongly affected by pH. The coconut-shell carbon (CSC) exhibited the
      highest lead adsorption capacity at pH 4.5. Isotherms for the adsorption of lead
      on CSC were developed and the equilibrium data fitted well to the Langmuir,
      Freundlich, and Tempkin isotherm models. At pH 4.5, the maximum lead adsorption
      capacity of CSC estimated with the Langmuir model was 26.50 mg g(-1) adsorbent.
      Energy of activation (Ea) and thermodynamic parameters such as DeltaG, DeltaH,
      and DeltaS were evaluated by applying the Arrhenius and van't Hoff equations. The
      thermodynamics of Pb(II) on CSC indicates the spontaneous and endothermic nature
      of adsorption. Quantitative desorption of Pb(II) from CSC was found to be 75%
      which facilitates the sorption of metal by ion exchange.

PMID- 15464795
TI  - Gallium(III) adsorption on carbonates and oxides: X-ray absorption fine structure
      spectroscopy study and surface complexation modeling.
AB  - Adsorption of Ga on calcite, magnesite, amorphous silica, and manganese oxide as
      a function of pH and gallium concentration in solution was studied using a batch
      adsorption technique. Adsorbed complexes of Ga on calcite, magnesite, and delta
      MnO2 were further characterized using XAFS spectroscopy. At high surface loadings
      from supersaturated solutions, Ga is likely to form a polymeric network at the
      surface (edge- and corner-sharing octahedra). At low surface loadings, Ga
      presents as isolated octahedra, probably attached to the Me-O sites on the
      surface, and coordinated by water molecules and hydroxide groups at 1.90-1.94 A.
      At pH>6, Ga therefore changes its coordination from 4 to 6 when adsorbing from
      solution (Ga(OH)(-)4(aq)) onto metal surface sites (MeOGa(OH)n(H2O)2-n(5-n), Me =
      Ca, Mg, or Mn, and n=1 and 2 for carbonate minerals and MnO2, respectively).
      Because the EXAFS is not capable of seeing hydrogen atoms, the protonation of
      surface complexes was determined by fitting the experimental pH-dependent Ga
      adsorption edge. A surface complexation model which assumes the constant
      capacitance of the electric double layer (CCM) and postulates the formation of
      positively charged, neutral and negatively charged surface complexes for
      carbonates, manganese oxide and silica, respectively, was used to describe the
      dependence of adsorption equilibria on aqueous solution composition in a wide
      range of pH and Ga concentration.

PMID- 15464796
TI  - Interaction of poly(ethylene oxide) with fumed silica.
AB  - Interaction of poly(ethylene oxide) (PEO, 600 kDa) with fumed silica A-300 (SBET
      = 316 m2/g) was investigated under different conditions using adsorption,
      infrared (IR), thermal analysis (TG-DTA), AFM, and quantum chemical methods. The
      studied dried silica/PEO samples were also carbonized in a flow reactor at 773 K.
      The structural characteristics of fumed silica, PEO/silica, and pyrocarbon/fumed
      silica were investigated using nitrogen adsorption-desorption at 77.4 K. PEO
      adsorption isotherm depicts a high affinity of PEO to the fumed silica surface in
      aqueous medium. PEO adsorbed in the amount of 50 mg per gram of silica (PEO
      monolayer corresponds to CPEO approximately 190 mg/g) can disturb approximately
      70% of isolated surface silanols. However, at the monolayer coverage, only 20% of
      oxygen atoms of PEO molecules take part in the hydrogen bonding with the surface
      silanols. An increase in the PEO amount adsorbed on fumed silica leads to a
      diminution of the specific surface area and contributions of micro- (pore radius
      R < 1 nm) and mesopores (1 < R < 25 nm) to the pore volume but contribution of
      macropores (R > 25 nm) increases with CPEO. Quantum chemical calculations of a
      complex of a PEO fragment with a tripple bond SiOH group of a silica cluster in
      the gas phase and with consideration for the solvent (water) effect show a
      reduction of interaction energy in the aqueous medium. However, the complex
      remains strong enough to provide durability of the PEO adsorption complexes on
      fumed silica; i.e., PEO/fumed silica nanocomposites could be stable in both
      gaseous and liquid media.

PMID- 15464797
TI  - Adsorption equilibrium modeling and solution chemistry dependence of fluoride
      removal from water by trivalent-cation-exchanged zeolite F-9.
AB  - Fluoride in drinking water above permissible levels is responsible for human
      dental and skeletal fluorosis. In this study, therefore, the large internal
      surface area of zeolite was utilized to create active sites for fluoride sorption
      by exchanging Na+-bound zeolite with Al3+ or La3+ ions. Fluoride removal from
      water using Al3+- and La3+-exchanged zeolite F-9 particles was subsequently
      investigated to evaluate the fluoride sorption characteristics of the sorbents.
      Equilibrium isotherms such as the two-site Langmuir (L), Freundlich (F), Langmuir
      Freundlich (LF), Redlich-Peterson (RP), Toth (T), and Dubinin-Radushkevitch (DR)
      were successfully used to model the experimental data. Modeling results showed
      that the isotherm parameters weakly depended on the solution temperature. From
      the DR isotherm parameters, it was considered that the uptake of fluoride by Al3+
      exchanged zeolite proceeded by an ion-exchange mechanism (E = 11.32-12.13
      kJ/mol), while fluoride-La3+-exchanged zeolite interaction proceeded by physical
      adsorption (E = 7.41-7.72 kJ/mol). Factors from the solution chemistry that
      affected fluoride removal from water were the solution pH and bicarbonate
      content. The latter factor buffered the system pH at higher values and thus
      diminished the affinity of the active sites for fluoride. Natural groundwater
      samples from two Kenyan tube wells were tested and results are discussed in
      relation to solution chemistry. In overall, Al3+-exchanged zeolite was found to
      be superior to La3+-exchanged zeolite in fluoride uptake within the tested
      concentration range.

PMID- 15464798
TI  - Electrical properties of multilayers from low- and high-molecular-weight
      polyelectrolytes.
AB  - The formation of stable multilayer films by using as constituents sodium poly(4
      styrene sulfonate) (PSS) and poly(4-vinyl pyridine) (PVP) was studied by
      electrooptics. A strong increase in basicity of the pyridine rings in the
      electrical field of the oppositely charged PSS chains was suggested to be the
      driving force for multilayer film formation. A linear increase in the film
      thickness was registered after deposition of the first three layers, with no
      dependence on the polyelectrolyte molecular weight. The electrooptical effect was
      found to increase with increasing area of each next layer, but depended on the
      molecular weights of both polymers. Polarization of "condensed" counterions along
      the chains of the last-adsorbed layer was suggested to explain this dependence.
      Following the counterion dynamics, we come to the conclusion that the electrical
      properties of the top layer govern the electrooptical behavior of the PSS/PVP
      film.

PMID- 15464799
TI  - Phenol adsorption onto powdered and granular activated carbon, prepared from
      Eucalyptus wood.
AB  - Eucalyptus grandis sawdust, a major waste from the growing Uruguayan wood
      industry, was used in previous work to prepare powdered activated carbon (PAC).
      In the present work, granular activated carbon (GAC) was prepared by mixing PAC,
      carboxymethyl cellulose as a binder, and kaolin as reinforcer. Ultimate analysis
      and surface characterization of GAC and PAC were performed. Phenol adsorption was
      used as a way to compare the characteristics of different PAC and GAC
      preparations. Kinetics and isotherms of the different GAC and PAC were performed
      in a shaking bath at 100 rpm and 298 K. Phenol concentrations were determined by
      UV spectroscopy. Some kinetics parameters were calculated; from kinetics results,
      external resistance to mass transfer from the bulk liquid can be neglected as the
      controlling step. Isotherms were fitted to Langmuir and Freundlich models, and
      corresponding parameters were determined. Maximum phenol uptakes for all carbons
      were determined and correlated with carbon characteristics. Thermogravimertic
      analysis (TGA) determinations were performed in order to study adsorption
      characteristics and conditions for GAC regeneration after its use. The results
      showed that phenol is preferentially physisorbed on the carbon of the granules,
      though some chemisorption was detected. No adsorption was detected in the kaolin
      carboxymethyl cellulose mixture.

PMID- 15464800
TI  - Surface properties and structures of diblock and random copolymers with
      perfluoroalkyl side chains.
AB  - Polymers with perfluoroalkyl side chains have recently attracted a great deal of
      interest as additives to surface hydrophobicity to values higher than these
      corresponding to polytetrafluoroethylene. The structure and surface free energy
      of random and diblock copolymers of methyl methacrylate and 2-perfluorooctylethyl
      methacrylate (PMMA-r-PFEMA and PMMA-b-PFEMA, respectively) were compared using
      dynamic contact angle, X-ray photoelectron spectroscopy, X-ray diffraction, and
      reflection-adsorption FT-IR spectroscopy. The PMMA-b-PFEMA solution cast film
      showed a surface free energy of 7.8 mJ/m2. This value was lower than that of PMMA
      r-PFEMA solution cast film (13.4 mJ/m2) but is comparable to the lowest value
      (6.7 mJ/m2) reported in literature. The surface of PMMA-b-PFEMA was almost
      covered with the CF3 groups of self-assembled perfluoroalkyl side chains. On the
      other hand, more CF2 groups and methacrylate main chain were exposed on the PMMA
      r-PFEMA film surface due to parallel orientation of the perfluoroalkyl side
      chains, which determined the relatively higher surface free energy of the PMMA-r
      PFEMA film.

PMID- 15464801
TI  - Preparation and characterization of nanocomposite polyurethane.
AB  - Polyurethane/nanosilica composites were prepared using polyester
      polyol/nanosilica composite resins obtained from in situ polymerization or
      blending methods and investigated by Fourier transform infrared spectra (FTIR),
      dynamical mechanical analysis (DMA), transmittance electron microscopy (TEM),
      contact angle measurement, X-ray photoelectron spectroscopy (XPS), and atomic
      force microscopy (AFM), respectively. It was found that more polyester segments
      had chemically bonded with silica particles during in situ polymerization than
      during blending, introducing nanosilica increased the Tgs of polyurethanes, and
      different preparation methods and different particle sizes caused various impact
      on Tg. Contact angle measurement and XPS analyses indicated that nanosilica
      tended to move towards the surfaces and interfaces of polyurethane coats,
      decreasing the free energies of the surfaces and interfaces, but the nanosilica
      particles were just observed at interfaces not surfaces by AFM.

PMID- 15464802
TI  - Temperature and concentration effects on supramolecular aggregation and phase
      behavior for poly(propylene oxide)-b-poly(ethylene oxide)- b-poly(propylene
      oxide) copolymers of different composition in aqueous mixtures, 1.
AB  - The phase behavior (temperature vs composition) and microstructure for the two
      binary systems Pluronic 25R4 [(PO)19(EO)33(PO)19]-water and Pluronic 25R2
      [(PO)21(EO)14(PO)21]-water have been studied by a combined experimental approach
      in the whole concentration range and from 5 to 80 degrees C. The general phase
      behavior has been identified by inspection under polarized light. Precise phase
      boundaries have been determined by analyzing 2H NMR line shape. The
      identification and microstructural characterization of the liquid crystalline
      phases have been achieved using small-angle X-ray scattering (SAXS). The
      isotropic liquid solution phases have been investigated by self-diffusion
      measurements (PGSE-NMR method). 25R2 does not form liquid crystals and is
      miscible with water in the whole concentration range; with increasing
      temperature, the mixtures split into water-rich and a copolymer-rich solutions in
      equilibrium. 25R4 shows rich phase behavior, passing, with increasing copolymer
      concentration, from a water-rich solution to a lamellar and copolymer-rich
      solution. A small hexagonal phase, completely encircled in the stability region
      of the water-rich solution, is also present. In water-rich solutions, at low
      temperatures and low copolymer concentrations, the copolymers are dissolved as
      independent macromolecules. With increasing copolymer concentrations an
      interconnected network of micelles is formed in which micellar cores of
      hydrophobic poly(propylene oxide) are interconnected by poly(ethylene oxide)
      strands. In copolymer-rich solutions water is molecularly dissolved in the
      copolymer. The factors influencing the self-aggregation of Pluronic R copolymers
      (PPO-PEO-PPO sequence) are discussed, and their behavior in water is compared to
      that of Pluronic copolymers (PEO-PPO-PEO sequence).

PMID- 15464803
TI  - Metal ion reduction and resultant deposition on viologen-functionalized LDPE
      films and viologen-containing microporous membranes.
AB  - Photo-induced reduction of gold and platinum metal salt solutions was carried out
      using viologen graft copolymerized on low-density polyethylene (LDPE) films and
      viologen-containing poly(vinylidene fluoride) (PVDF-PVBV) microporous membranes.
      The effects of the UV irradiation time and concentration of the metal salt
      solutions on the metal ion reduction process and the resultant metal deposition
      on the polymeric substrates were investigated. The metal-polymer composites were
      characterized using X-ray photoelectron spectroscopy (XPS), scanning and
      transmission electron microscopy (SEM and TEM), atomic force microscopy (AFM),
      energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and UV
      visible absorption spectroscopy. The amount of metal uptake, the state of the
      metal, and the size of the metal particles were found to be strongly dependent on
      the UV irradiation time and the type and concentration of the metal salt
      solution. The microporous structure and the high viologen content of the PVDF
      PVBV membrane constitute an effective matrix for metal ion reduction and
      preparation of metal nanoparticles.

PMID- 15464804
TI  - Investigating porcine pancreatic phospholipase A2 action on vesicles and
      supported planar bilayers using a quartz crystal microbalance with dissipation.
AB  - We present an investigation of the activity of porcine pancreatic phospholipase
      A2 towards phospholipids. The phospholipids are presented in three different
      ways, namely as tethered vesicles, intact surface-bound vesicles, and supported
      planar bilayers (SPBs). The process is followed using a quartz crystal
      microbalance which measures both the frequency shift and the energy dissipation
      factor. This technique is very sensitive not only to the mass of the material
      deposited on the crystal, but also to its viscoelasticity. The breakdown of the
      phospholipid vesicles and bilayers consequently gives rise to very large signal
      changes. Enzyme binding is separated from vesicle hydrolysis using
      nonhydrolyzable ether lipids. Intact and tethered vesicles give rise to the same
      profile, indicating that direct immobilization of the vesicles does not affect
      hydrolysis significantly. The data fit well to a Voight-based model describing
      the change in film structure with time. Initial enzyme binding to intact vesicles
      is accompanied by a significant increase in layer thickness as well as a decrease
      in viscosity and shear modulus. This effect, which is less pronounced in SPBs, is
      probably mainly due to the accumulation of hydrolysis products in the vesicle
      prior to rupture of the vesicles and release of bound water, since it disappears
      when lysolipid is included in the vesicles prior to hydrolysis.

PMID- 15464805
TI  - Significance of cell electrokinetic properties determined by soft-particle
      analysis in bacterial adhesion onto a solid surface.
AB  - The influence of extracellular polymeric substances (EPSs) on bacterial cell
      electrokinetic properties and on cell adhesion onto glass beads in connection
      with bacterial cell electrokinetic properties was investigated using 12
      heterotrophic bacterial strains. Bacterial cell surface properties such as the
      softness 1/lambda and charge density ZN were determined by Ohshima's soft
      particle analysis using the measured electrophoretic mobility as a function of
      ionic strength. In 10 of 12 strains, when EPSs covering the cell surface were
      removed, the softness of the cell decreased, indicating that EPS adsorption
      enhanced the ease of liquid fluid in the ion-penetrable layer on the cell
      surface. On the other hand, the negative charge density of the cell surface
      increased for 9 of 12 strains, suggesting that EPSs covering the cell surface
      decreased the negative charge density of the cell surface layer. In addition, the
      characteristics of bacterial cell adhesion onto glass beads were evaluated by the
      packed-bed method and the data were interpreted to indicate cell adhesiveness. As
      a result, the efficiency of cell adhesion onto glass beads increased as negative
      cell surface potential psi0 decreased, whereas there seemed to be no correlation
      between zeta potential and cell adhesiveness. Cell surface potential psi0, which
      was derived by taking the bacterial polymer layer with EPSs into consideration,
      provided a more detailed understanding of the electrokinetic properties of
      bacterial cells.

PMID- 15464806
TI  - Use of analytical microscopy to analyze the speciation of copper and chromium
      ions onto a low-cost biomaterial.
AB  - In this paper, we present our study of the speciation of copper and hexavalent
      chromium sorbed onto a lignocellulosic substrate, using analytical microscopy.
      The lignocellulosic substrate constitutes a low-cost biomaterial that can be used
      in wastewater treatment. Transmission electron microscopy (TEM) coupled with
      energy-dispersive X-ray spectroscopy (EDXS) was used to determine the speciation
      of the two metal ions on the constitutive moieties of the lignocellulosic
      substrate. The use of a staining agent sensitive to carbon unsaturation allowed
      us to differentiate between the microstructures rich in lignin entities and those
      rich in cellulose entities. The EDX analysis showed that metal ions are
      preferentially sorbed onto microstructures rich in lignin moieties. The energy
      electron loss spectroscopy (EELS) was used to determine the oxidation states of
      chromium in association with lignocellulosic moieties. We showed that the
      sorption process of hexavalent chromium requires the reduction of Cr(VI) into
      Cr(III) and the probable oxidation of lignin moieties.

PMID- 15464807
TI  - Fishing of beta-amylase with a SAM of alpha-cyclodextrin-poly- (ethylene glycol)
      conjugate.
AB  - Alpha-cyclodextrin (alpha-CD) with an amino group was conjugated to an alpha,
      omega-dicarboxylated poly(ethylene glycol) (PEG). The inhibition constant (Ki) of
      the alpha-CD-PEG conjugate for the catalysis by beta-amylase was larger than that
      of alpha-CD, due to a steric obstruction of the PEG moiety to the binding of
      alpha-CD moiety to beta-amylase. alpha-CD-PEG was further modified with cystamine
      (CD-PEG-Cys) or cysteamine methyl disulfide (CD-PEG-MDS), and the disulfide
      carrying alpha-CD-PEG was accumulated on a gold surface as a self-assembled
      monolayer (SAM). The binding of beta-amylase to the alpha-CD-PEG SAM was followed
      by a decrease in cathodic peak current in the voltammogram of hydroquinone as a
      probe using a cyclic voltammetry (CV). The beta-amylase bound to the alpha-CD-PEG
      SAM was desorbed by the addition of free alpha-CD, and the ratio of desorbed beta
      amylase from the SAM of alpha-CD-PEG-Cys to the total amount of the enzyme bound
      to the SAM was 40% whereas that from the alpha-CD-PEG-MDS SAM was 83-85%. The
      percentage of desorption was increased to 100% by the treatment of the alpha-CD
      PEG-MDS SAM-carrying electrode with 2-hydroxyethyldisulfide prior to the
      immersion in the enzyme solution. Adsorption and desorption processes of beta
      amylase to the surface of alpha-CD-PEG-MDS SAM were clearly observed using
      localized surface plasmon resonance absorption spectroscopy. The binding constant
      of the enzyme to the surface-confined alpha-CD-PEG was much larger than that to
      free alpha-CD, probably due to a large local concentration of the alpha-CD moiety
      on the gold surface.

PMID- 15464808
TI  - Synthesis of Ag/Pd nanoparticles via reactive micelles as templates and its
      application to electroless copper deposition.
AB  - Ag/Pd nanoparticles have been synthesized with a reactive alcohol-type
      surfactant, sodium dodecyl sulfate (SDS), without the presence of an external
      reducing agent. Both UV-vis absorption spectra and X-ray diffraction patterns for
      the bimetallic and physical mixtures of individual nanoparticles revealed the
      formation of a bimetallic structure. Based on this method, an ordered 3D
      grapelike nanostructure was formed, possibly due to transformation of the liquid
      crystal phase of the micelles. Data from the energy-dispersive X-ray analysis
      show that the composition of bimetallic nanoparticle is approximately equal to
      the feeing solution. Furthermore, the Ag/Pd nanoparticles exhibit distinct
      catalyst for electroless copper deposition and may be a substitute for the
      conventional palladium system, which is expensive and unstable in operation.

PMID- 15464809
TI  - Aggregate restructuring by polymer solvency effects.
AB  - This study investigates the aggregation in cyclohexane of silica particles
      initially stabilized by grafted polystyrene and destabilized by temperature
      reduction. It complements an earlier study by Zhu and Napper (P.W. Zhu, D.H.
      Napper, Phys. Rev. E 50 (1994) 1360) in which the aggregation of polystyrene
      latex particles with tethered poly(N-isopropyl acrylamide) (PNIPAM) in water was
      investigated. Their dynamic light scattering results showed that both the rate of
      aggregation and the aggregate fractal dimension increased with a sufficient
      decrease in the PNIPAM adlayer solvency, achieved by means of either salt (NaNO3)
      addition or temperature rise. This result stands in contrast to those obtained
      when an electrostatically stabilized colloid is destabilized, i.e., that the more
      rapidly aggregates are formed, the lower the resulting fractal dimension. The
      authors explained their results in terms of the effects of both salt effects and
      increased temperature on the extent of the hydrophobic interactions between the
      adlayer-covered surfaces in the water. The present study examines a sterically
      stabilized colloid in a nonaqueous solvent, where neither salt effects nor
      hydrophobic effects play a role. Temperature is decreased to bring the system
      from better-than-theta-conditions to worse-than-theta-conditions. Power-law
      aggregation kinetics are observed at 15.7 degrees C by dynamic light scattering.
      The particles first undergo reduced rate aggregation, producing low-fractal
      dimension aggregates, which after some time, restructure into more compact aged
      clusters. The fractal dimension of these aged clusters increases with increasing
      initial aggregation rate, consistent with results seen by Zhu and Napper, but
      without the presence of hydrophobic effects. The ability of the polymer-grafted
      particles to rearrange suggests aggregation into a secondary minimum, with the
      ability to slide over one another to achieve a more energetically favorable,
      denser configuration. The reversible nature of the aggregation is verified by
      additional experiments gradually bringing the system from worse-than-theta
      conditions back to better-than-theta-conditions, with an attendant decrease in
      aggregate fractal dimension, and ultimately full redispersion.

PMID- 15464810
TI  - Colloid-polymer mixtures in solution with refractive index matched acrylate
      colloids.
AB  - Colloid-polymer (CP) mixtures extend between two limiting cases, the colloid
      limit with the polymer coil size small compared to the colloid radius Rcol and
      the protein limit with the colloidal particles much smaller in size than the
      radius of gyration of the polymer chains Rg. In the present work, model systems
      are developed for the protein limit. The colloid-solvent pairs are optimized in
      terms of their isorefractivity in order to facilitate the characterization of
      large polystyrene chains in suspensions of small colloids. The degree of
      isorefractivity of colloidal particles was successfully evaluated in terms of a
      reduced scattering intensity. Two polystyrene samples with radii of gyration of
      Rg = 96 nm and Rg = 78 nm, respectively, are used. The radii of the colloidal
      particles are close to Rcol = 12 nm, leading to size ratios of Rg/Rcol = 8 and
      Rg/Rcol = 6.5. Four colloid solvent systems were found to be suitable for polymer
      characterization by light scattering, one based on silica particles and three
      systems with acrylate particles. The present investigation is focused on the
      three acrylate systems: poly(methyl methacrylate) in ethyl benzoate (ETB) at 7
      degrees C, poly(ethyl methacrylate) in toluene at 7 degrees C and poly(ethyl
      methacrylate) in ETB at 40 degrees C. Characterization of PS chains is for the
      first time performed in colloid concentrations up to 2.5% by weight. In all
      cases, the size and shape of the polymer chains remain unchanged. A slight
      mismatch of the colloid scattering or a limited colloid solubility prevented
      investigation of PS chains at higher colloid concentration.

PMID- 15464811
TI  - In situ approaches to establish colloidal growth kinetics.
AB  - A technique based on the back scattering phenomenon of dynamic light scattering
      has been employed to monitor the kinetics of gold and platinum metal nanoparticle
      growth and silver nanoparticle oxidation as well as in the determination of
      particle sizes ranging from 1 to 200 nm in diameter. The systems were chosen to
      examine the applicability of dynamic light scattering to nanoresearch over a
      broad range of sizes as well as both metallic and nonmetallic systems. The
      advantages of this instrumentation over traditional instruments such as X-ray
      diffraction (XRD), transmission electron microscopy (TEM), and scanning electron
      microscopy (SEM) have been highlighted.

PMID- 15464812
TI  - Dispersion polymerization of methyl methacrylate with a novel bifunctional
      polyurethane macromonomer as a reactive stabilizer.
AB  - A novel macromonomer of vinyl-terminated bifunctional polyurethane was
      synthesized and applied to the dispersion polymerization of MMA in ethanol. The
      existence of the vinyl terminal groups and the grafted macromonomer with PMMA was
      verified using 1H NMR and 13C NMR. The stable and monodisperse PMMA microspheres
      having a weight-average diameter of 5.09 microm and a good uniformity of 1.01
      were obtained with 20 wt% polyurethane macromonomer. The molecular weight
      increased, but the size of the synthesized PMMA microspheres decreased with the
      macromonomer concentration since the macromonomer acts as a reactive stabilizer
      in dispersion polymerization. Furthermore, the molecular weight of the PMMA
      prepared by the use of the macromonomer was approximately twofold higher than
      that prepared by a conventional stabilizer, poly(N-vinylpyrrolidone). The higher
      molecular weight is thought to originate from the grafting and a possibly slight
      crosslinking of PMMA molecules due to the bifunctional reactive groups at the
      ends of macromonomer chains.

PMID- 15464813
TI  - Three-dimensional colloidal crystals with a well-defined architecture.
AB  - Monodisperse silica spheres with diameters of 220-1100 nm were prepared by
      hydrolysis of tetraethyl orthosilicate (TEOS) in an alcoholic medium in the
      presence of water and ammonia. By grafting vinyl or amino groups onto silica
      surfaces using the coupling agents allyltrimethoxysilane and
      aminopropyltriethoxysilane, respectively, amphiphilic silica spheres were
      obtained and could be organized to form a stable Langmuir film at the air-water
      interface. The controlled transfer of this monolayer of particles onto a solid
      substrate gave us the ability to build three-dimensional regular crystals with a
      well-defined thickness and organization. These colloidal crystals diffract light
      in the UV, the visible, and the near-infrared (NIR) spectral regions, depending
      on the size of the silica spheres and according to Bragg's law. The depth of the
      photonic stop band can be tuned by varying the number of deposited layers of
      particles. By using successive depositions, we could prepare multilayered films
      with silica spheres of different sizes. The thickness of each slab in the binary
      crystals can be tuned at the layer level, while the crystalline order of each
      layer is well preserved.

PMID- 15464814
TI  - Correlation between dispersion properties of TiO2 colloidal sols and
      photoelectric characteristics of TiO2 films.
AB  - TiO2 film for use as dye-sensitized solar cell was prepared using the TiO2
      colloidal sols (unpeptized sol and peptized sol). The optical properties and
      photocurrent-voltage characteristics of the resultant films were investigated.
      The optical transmittance of TiO2 thin film prepared from the peptized colloidal
      sol was over 90%, while that of TiO2 film from the unpeptized sol was under 80%.
      The TiO2 photoelectrode prepared from the peptized colloidal sol showed low
      photoelectric conversion efficiency (eta), 1.30%, whereas the efficiency of
      photoelectrode from the unpeptized sol was 2.21%. The high optical transmittance
      and low conversion efficiency of TiO2 film from the peptized sol are discussed in
      terms of dense microstructure due to the drying nature of well-dispersed
      colloidal sol.

PMID- 15464815
TI  - Poly(ethylene oxide) thin films produced by electrospray deposition: morphology
      control and additive effects of alcohols on nanostructure.
AB  - Nanostructured thin films were prepared by electrospray deposition (ESD) from
      poly(ethylene oxide) (PEO) aqueous solution. The surface morphologies of the
      deposited films were observed using scanning electron microscopy (SEM). The SEM
      images revealed the correlations between the morphologies and the ESD conditions.
      By changing the applied voltage and solution properties such as viscosity,
      surface tension, conductivity, and molecular weight, PEO thin films with diverse
      nanostructures--from nanospheres to nanofibers--were fabricated. It was also
      revealed that the addition of alcohols to polymer solution, which enables
      simultaneously changing the viscosity, the surface tension, and the conductivity,
      enhanced the formation of the fibrous structure. These results indicate that the
      ESD method is potentially a useful option for producing nanoengineered polymer
      surface.

PMID- 15464816
TI  - Contact angle measurements with liquids consisting of bulky molecules.
AB  - Well-measured contact angles with different solid-liquid systems fall
      approximately on smooth patterns when plotted versus liquid surface tension.
      However, there are deviations of 1 degrees -3 degrees , which are outside the
      error limits. It is the purpose of this paper to elucidate the reasons for such
      deviations. Two types of liquids were selected for advancing contact angle
      measurements on Teflon AF 1600 coated surfaces: a series of n-alkanes ranging
      from n-hexane to n-hexadecane and five liquids consisting of bulky molecules,
      octamethylcyclotetrasiloxane (OMCTS), methyl salicylate, tetralin, cis-decalin,
      and octamethyltrisiloxane (OMTS). It was found that contact angles of the liquids
      with bulky molecules fall on a perfectly smooth curve corresponding to a solid
      surface tension of 13.64 +/- 0.1 mJ/m2. However, contact angles of n-alkanes
      deviated from this curve by up to 3 degrees in a complicated fashion. The
      observed trend suggests that more than one mechanism is responsible for the
      deviations. Substrate-induced rearrangement of liquid molecules in the close
      vicinity of the surface in the case of long-chain n-alkanes and adsorption of
      vapor onto the solid surface in the case of short-chain n-alkanes are the most
      likely explanations. The results suggest that liquids with bulky molecules appear
      to be suitable for contact angle measurements to characterize energetics of
      polymeric surfaces.

PMID- 15464817
TI  - Synchronized motion of a mobile boundary driven by a camphor fragment.
AB  - The synchronized self-motion of a camphor fragment and a mobile boundary on a
      water surface depending on the initial conditions and the asymmetry of the
      boundary was investigated. When a camphor fragment, which showed unidirectional
      rotation, was surrounded by a circular ring as a symmetric mobile boundary on a
      water surface, the circular ring also rotated but in the direction opposite to
      that of the camphor fragment. The velocity of the rotation of the mobile ring
      varied depending on the anisotropy of the shape of the ring. When a camphor
      fragment was placed on the inside of a circular ring floating on the water
      surface, the ring and camphor fragment exhibited translational motion without
      rotation. These characteristics of synchronized self-motion are discussed in
      relation to the surface tension as the driving force and convective flow due to
      the gradient of the surface-active camphor layer.

PMID- 15464818
TI  - Surface free energies of silica fillers and their relation to the adsorption of
      poly(ethylene terephthalate).
AB  - The surface free energy of modified silica as well as of PET oligomers was
      evaluated through measurements of specific retention volumes of several probe
      molecules by use of the adsorption and adhesion principles in inverse gas
      chromatography. The nondispersive component of surface free energy of most silica
      fillers was larger than the dispersive component and the acidic component was
      much larger than the basic one, which indicated that the surfaces of most silica
      fillers were rather acidic. These methods were also applied to PET oligomer and
      it was found that the surface free energy of PET oligomer, regardless of
      preparation method, consisted of an almost dispersive component, suggesting that
      the surface of PET was neutral. The amount of PET oligomer adsorbed for the heat
      treated silica fillers in acidic solvent increased linearly with increased acidic
      component of the surface free energy, which indicates that the acidic component
      of the surface free energy may be responsible for the adsorption. However, the
      adsorption amount on modified silica is much smaller than that for the heat
      treated silica fillers because of steric hindrance caused by the attached organic
      chain, suggesting that the adsorption cannot be determined only by the surface
      free energy.

PMID- 15464819
TI  - Wetting kinetics of modified polyimide surfaces: interactions with polar
      solvents.
AB  - Contact angle relaxation studies were performed on a base hydrolyzed PMDA-ODA
      polyimide surface using methanol, pyridine and 1-methyl-2-pyrrolidinone (NMP) as
      probe liquids. The results were fitted parametrically to the molecular-kinetic
      theory to obtain the relevant molecular parameters that govern wetting rates. The
      probe liquid NMP appeared to have the greatest interaction of the three solvents
      studied with the modified polyimide surface. The differences in wetting rates are
      explained to result from the hydrogen bonding capability of the probe liquids
      with the modified polyimide surface and due to the difference between bulk and
      surface pKa of the modified polyimide.

PMID- 15464820
TI  - Physicochemical characteristics of reverse micelles of polyoxyethylene nonyl
      phenol in different organic solvents.
AB  - The association of polyoxyethylene nonyl phenol (Igepal) in four different
      organic solvents such as chloroform, carbon tetrachloride, cyclohexane, and
      heptane has been studied. The critical micellar concentration of the reverse
      micelle (RM) formed in different nonaqueous media has been determined using four
      different techniques: UV-visible spectroscopy, fluorescence spectroscopy, Stokes
      shift, and NMR spectroscopic studies. From the correlation of cmc with hydrophile
      lipophile balance (HLB), we have found that cmc decreases with decrease in HLB.
      The obtained cmc values using different methods have been found to be consistent
      and facilitate the determination of DeltaG values associated with the
      micellization. The association constant of the dye molecule Safranine T (ST) with
      the reverse micelle, aggregation number of the surfactant monomer, and location
      of fluorophore in the RM have been determined. The vertical ionization potential
      of Igepal, electron affinity of the dye, and the degree of charge transfer have
      been estimated by the theoretical AM1 calculations. A linear relationship has
      been obtained between cmc(s) and the ionization potential of the solvents. The
      polarity of the micelle solubilization sites has been determined from the
      solvatochromic shift, Kosower Z value, and ET(30) value.

PMID- 15464821
TI  - Mixed micelles of sodium 4-decyl naphthalene sulfonate with Triton X-100 and
      sodium dodecyl sulfonate analyzed by 1H NMR.
AB  - The characteristics of sodium 4-decyl naphthalene sulfonate (SDNS)/Triton X-100
      (TX-100) and sodium dodecyl sulfonate (SDSN)/SDNS mixed micelles with different
      molar ratios were studied by 1D and 2D 1H NMR. In the mixed micelle of SDNS/TX
      100 the phenoxy rings of the TX-100 are embedded in the near vicinity of the
      alkyl chains of SDNS and its polyoxyethylene segments, but the first oxyethylene
      group, to which the phenoxy ring is adjacent, are located near the naphthyl
      rings. In the mixed micelle of the SDNS/SDSN system the sulfonate groups of SDSN
      are embedded in the naphthyl rings of SDNS; i.e., they are located more
      internally in the mixed hydrophobic micellar core than those of SDNS. Moreover,
      the naphthyl rings of SDNS separating these sulfonate groups of SDSN may play an
      active role in weakening the electrostatic repulsion of the negatively charged
      sulfonate groups, which favors the mixed micelle aggregation.

PMID- 15464822
TI  - Defoaming effect of calcium soap.
AB  - The effect of calcium oleate on foam stability was studied for aqueous solutions
      of two commonly used surfactants (anionic and nonionic) under alkaline conditions
      in the absence of oil. For the anionic surfactant, defoaming by calcium oleate
      appears to involve two mechanisms. One is that oleate and calcium ions are
      presumably incorporated into the surfactant monolayers with a resulting decrease
      in the maximum of the disjoining pressure curve and therefore produces less
      stable thin films. The other is bridging of the films by calcium oleate
      particles. The latter mechanism was especially important in freshly made
      solutions where precipitation in the aqueous phase was still occurring when the
      foam was generated. Foams generated after aging (hours) when precipitation was
      nearly complete were more stable even though solution turbidities were greater.
      Foams of the nonionic surfactant were less stable than those of the anionic
      surfactant but were also destabilized by sufficient amounts of calcium oleate and
      exhibited a similar aging effect. A simplified model was developed for estimating
      the sodium oleate concentration at which precipitation commences in solutions of
      the anionic surfactant containing dissolved calcium. It includes enhancement of
      calcium content in the electrical double layers of the surfactant micelles.
      Predictions of the model were in agreement with experiment.

PMID- 15464823
TI  - Synthesis and properties of N-hexadecyl ethylenediamine triacetic acid.
AB  - A new kind of surfactant named N-hexadecyl ethylenediamine triacetic acid (HED3A)
      was synthesized from anhydrous ethylenediamine, 1-bromohexadecane, and
      chloroacetic acid. Testing showed stability of HED3A in hard water, wetting
      power, dispersing power, and surface tension increased along with pH value.
      Stability in hard water of trisodium N-hexadecyl ethylenediamine triacetate
      (3NaHED3A) was at level 4, which was better than that of sodium dodecylsulfate
      (SDS) and sodium dodecylbenzene sulfonate (LAS). Other properties of 3NaHED3A
      including wetting power, dispersing power, emulsifying power, and surface tension
      had intermediate value between SDS, LAS, AES, peregal-O, and
      cetyltrimethylammonium chloride (CTAC). The ethylenediamine triacetic acid (ED3A)
      group in 3NaHED3A can chelate many kinds of metal ions, which indicates a
      promising application prospect in many fields including metal anticorrosion,
      corrosion control agent, additives in electroplating solution, and ore selection
      and solid surface treatment.

PMID- 15464824
TI  - Semifluorinated chains in 2D-(perfluorododecyl)-alkanes at the air/water
      interface.
AB  - Langmuir monolayers of a homologous series of perfluorododecyl-n-alkanes (general
      formula F(CF2)12(CH2)nH, abbreviated as F12Hn, where n = 6-20) are investigated
      through isotherms of surface pressure (pi) and electric surface potential
      (DeltaV) versus area (A) and quantitative Brewster angle microscopy. The
      investigated monolayers are found to be liquid in nature. The negative sign of
      the measured surface potential evidences the orientation of all the investigated
      molecules with their perfluorinated parts directed toward the air regardless of
      the length of the hydrogenated unit. Analysis of the direction of the molecular
      dipole moment with respect to the main axis indicates that the minimum effective
      dipole moment is achieved for a molecule oriented at an angle of about 35 degrees
      to the surface normal. The film thickness was evaluated from the relative
      intensity measurements. The results suggest that the F12Hn molecules are tilted
      to the interface in the vicinity of collapse, which is in accordance with the
      liquid character of their monolayers.

PMID- 15464825
TI  - Solubilization of negatively charged DPPC/DPPG liposomes by bile salts.
AB  - The interactions of the bile salts sodium cholate (NaC) and sodium deoxycholate
      (NaDC) in 0.1 M NaCl (pH 7.4) with membranes composed of 1,2-dipalmitoyl-sn
      glycero-3-phosphatidylcholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3
      phosphatidylglycerol (DPPG) and mixtures of DPPC and DPPG at molar ratios of 3:1
      and 1:1 were studied by means of high-sensitivity isothermal titration
      calorimetry (ITC), dynamic light scattering (DLS), and differential scanning
      calorimetry (DSC). The partition coefficients and the transfer enthalpies for the
      incorporation of bile salt molecules into the phospholipid membranes were
      determined by ITC. The vesicle-to-micelle transition was investigated by ITC,
      DLS, and DSC. The phase boundaries for the saturation of the vesicles and their
      complete solubilization established by ITC were in general agreement with DLS
      data, but systematic differences could be seen due to the difference in detected
      physical quantities. Electrostatic repulsion effects between the negatively
      charged bile salt molecules and the negatively charged membrane surfaces are not
      limiting factors for the vesicle-to-micelle transition. The membrane packing
      constraints of the phospholipid molecules and the associated spontaneous
      curvature of the vesicles play the dominant role. DPPG vesicles are transformed
      by the bile salts into mixed micelles more easily or similarly compared to DPPC
      vesicles. The saturation of mixed DPPC/DPPG vesicles requires less bile salt, but
      to induce the solubilization of the liposomes, significantly higher amounts of
      bile salt are needed compared to the concentrations required for the
      solubilization of the pure phospholipid systems. The different solubilization
      behavior of DPPC/DPPG liposomes compared to the pure liposomes could be due to a
      specific "extraction" of DPPG into the mixed micelles in the coexistence region.

PMID- 15464826
TI  - Influence of 8-bromo-cyclicAMP on interleukin -6 and -8 mRNA levels in A549 human
      lung epithelial cells exposed to organic dust: a time-kinetic study.
AB  - Exposure in a swine confinement building of previously unexposed subjects leads
      to an intense inflammatory reaction with increased number of inflammatory cells
      and mediators in the upper and lower respiratory tract. In vitro the organic dust
      induces cytokine release from respiratory epithelial cells. Whether the dust
      induced release of IL-6 and IL-8 protein from A549 lung epithelial cells is a
      result of sustained mRNA expression during the 24 h exposure generally applied is
      unknown. Furthermore, it is not known if the previously demonstrated effects on
      basal and dust-induced IL-6 and IL-8 protein production by 8-bromo-cyclicAMP are
      time-dependent, since only cumulative effects are observed by measurement of
      cytokine release. In the present study reverse transcription- (RT-) PCR was
      applied to investigate expression of IL-6 and IL-8 mRNA in A549 cells exposed to
      organic dust in a time-kinetic manner. The dust increased IL-6 and IL-8 mRNA
      expression at all times tested (1 h-48 h). The IL-6 mRNA expression peaked at 1
      1.5 h and was reduced with time, whereas the dust-induced IL-8 mRNA expression
      remained elevated. At 1-1.5 h, 8-bromo-cAMP stimulated basal and dust-induced IL
      6 mRNA expression and attenuated dust-induced IL-8 mRNA expression by activation
      of protein kinase A- (PKA), as assessed with the PKA inhibitor H-89. On prolonged
      exposure (>3 h), the dust-induced IL-6 mRNA was PKA-dependently decreased,
      whereas at 17 h and longer the IL-8 mRNA expression induced by a dust-suspension
      with 8-bromo-cAMP was similar to, or enhanced, relative to the dust-induced IL-8
      mRNA. Thus, 8-bromo-cAMP exerted opposite action on dust-induced IL-6 and IL-8
      mRNA expression with time.

PMID- 15464827
TI  - Attenuation of cocaine-induced conditioned place preference by Polygala
      tenuifolia root extract.
AB  - A recent investigation indicated that Polygala tenuifolia Willdenow extract (PTE)
      possesses a potential antipsychotic effect. In this study, we examined the
      effects of PTE on the cocaine-induced changes in locomotor activity, conditioned
      place preference (CPP), fos-related antigen-immunoreactivity (FRA-IR), and
      activator protein (AP)-1 DNA binding activity. Cocaine-induced behavioral effects
      (hyperlocomotion and CPP) occurred in parallel with increases in FRA-IR and AP-1
      DNA binding activity in the nucleus accumbens. These responses induced by cocaine
      were consistently attenuated by concurrent treatment with PTE (25 mg or 50
      mg/kg/day, i.p. x 7). The adenosine A2A receptor antagonist, 1,3,7-trimethyl-8-(3
      chlorostyrl)xanthine (0.5 or 1.0 mg/kg, i.p.), reversed the PTE-mediated
      pharmacological action in a dose related manner; neither the adenosine A(1)
      receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (0.5 or 1.0 mg/kg, i.p.)
      nor the A2B receptor antagonist, alloxazine (1.5 or 3.0 mg/kg, i.p.)
      significantly affected this pharmacological action. Our results suggest that PTE
      prevents cocaine-induced behavioral effects, at least in part, via the activation
      of the adenosine A2A receptor.

PMID- 15464828
TI  - Peroxynitrite but not nitric oxide donors destroys epinephrine: HPLC measurement
      and rat aorta contractility.
AB  - Nitric oxide (NO) and peroxynitrite (ONOO) have been reported to destroy
      catecholamines. We compared the ability of NO donors and peroxynitrite to
      decompose epinephrine in both chemical and pharmacological experiments.
      Epinephrine (1 microM) was incubated with NO donors (SNAP and MAHMA NONOate) and
      ONOO at a concentration of 0.1 mM in phosphate buffer (pH 7.4; 0.1 M) or Krebs
      solution for 10 minutes at 37 degrees C. HPLC revealed that the concentration of
      epinephrine in the presence of NO donors was unaltered. In contrast,
      peroxynitrite decreased epinephrine concentration more than 20 fold. Similar
      relationships were obtained in the study of rat thoracic aorta ring contraction.
      The contractile activity (EC50) of epinephrine in control solutions and after
      incubation of NE with NO donors did not change. EC50 was measured at 8-10 nM in
      control solutions and after preincubation with NO donors. However when
      epinephrine was preincubated with peroxynitrite, no contractile effect was
      evoked. Therefore, under these experimental conditions peroxynitrite, but not NO
      donors, was capable of destroying epinephrine.

PMID- 15464829
TI  - DHEAS improves learning and memory in aged SAMP8 mice but not in diabetic mice.
AB  - Dehydroepiandrosterone sulfate (DHEAS) has been reported to improve memory in
      aged animals and suggested as a treatment for age-related dementias. The SAMP8
      mouse, a model of Alzheimer's disease, has an age-related impairment in learning
      and memory and an increase in brain levels of amyloid precursor protein (APP) and
      amyloid beta protein (Abeta). Male SAMP8 mice also have a decrease in
      testosterone, to which DHEA is a precursor. Diabetes has been suggested as a
      model of aging and to be linked to Alzheimer's disease. Diabetics can have memory
      deficits and lower DHEAS levels. Here, we examined the effects of chronic oral
      DHEAS on acquisition and retention for T-maze footshock avoidance in 12 mo male
      SAMP8 mice and in CD-1 mice with streptozocin-induced diabetes. Learning and
      memory were improved in aged SAMP8 mice, but not in CD-1 mice with streptozocin
      induced diabetes. These findings suggest that DHEAS is more effective in
      reversing the cognitive impairments associated with overexpression of Abeta than
      with diabetes.

PMID- 15464830
TI  - Anxiolytic-like effects of extracts from Albizzia julibrissin bark in the
      elevated plus-maze in rats.
AB  - The purpose of the this study was to characterize the putative anxiolytic-like
      effects of the aqueous extract of Albizzia julibrissin stem bark using the
      elevated plus maze (EPM) in rats. The water extract of Albizzia julibrissin was
      orally administered at 10, 50, 100 or 200 mg/kg to adult male SD rats, 1 h before
      behavioral evaluation in an EPM, respectively. Control rats were treated with an
      equal volume of saline, and positive control rats buspirone (1 mg/kg). Single or
      repeated treatment (for 7 days) of the water extract of Albizzia julibrissin (at
      100 or 200 mg/kg) significantly increased time-spent and arm entries into the
      open arms of the EPM, and decreased time-spent and arm entries in the closed arms
      of the EPM versus saline controls (P < 0.05). However, no changes in the
      locomotor activity and myorelaxant effect were seen in any group versus the
      saline control. In addition, the anxiolytic-like effects of Albizzia julibrissin
      extract were abolished by pindolol (10 mg/kg, i.p), a 5-HT(1A/1B) receptor
      antagonist. These results suggest that Albizzia julibrissin might proved to be an
      effective anxiolytic agent, and that it acts via the serotonergic nervous system.

PMID- 15464831
TI  - Streptozotocin-induced diabetes in the pregnant rat reduces 11 beta
      hydroxysteroid dehydrogenase type 2 expression in placenta and fetal kidney.
AB  - Several epidemiological and animal studies have shown that the offsprings of
      diabetic mothers have higher incidences of glucose intolerance, obesity, insulin
      resistance, and hypertension in later life. It is well known that glucocorticoid
      metabolism plays a crucial role on several adult disease originated from fetal
      environment. The aim of this study was to investigate the relation between
      diabetic pregnancy and glucocorticoid metabolism of both mother and fetus,
      focusing on the 11 beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2. A model
      of diabetic pregnancy was made by intravenous injection of streptozotocin (35
      mg/kg body weight) to Sprague-Dawley rats, and blood and tissue samples were
      collected on day 20 of pregnancy. In the diabetic group, expression of 11 beta
      hydroxysteroid dehydrogenase type 2 in placentas and fetal kidneys was decreased
      remarkably. Corticosterone levels of diabetic mothers were lower than those of
      control rats. Despite the differences in maternal corticosterone levels, fetal
      levels of corticosterone did not differ between the groups. Our results lend
      support to the concept that diabetic pregnancy imprints glucocorticoid regulation
      in these fetuses, which may contribute to their increased incidence of higher
      blood pressure as adults.

PMID- 15464832
TI  - Prevention by celecoxib of secondary hyperalgesia induced by formalin in rats.
AB  - Administration of formalin in rat paws results in stimulation of nociceptive
      pathways, which leads to an increase in the excitability of neurons present in
      dorsal horn. This increased neuron excitability, described as central
      sensitization, may result in development of inflammatory pain at a distant site
      of injury application, known as secondary hyperalgesia. The aim of the present
      study was to verify whether formalin injection in rat paws would lead to
      secondary hyperalgesia development, as measured by the tail-flick test. We also
      aimed to investigate whether celecoxib, a specific cyclooxygenase 2 (COX-2)
      inhibitor, would affect secondary hyperalgesia. Formalin injected into the rat
      paws significantly reduced the latency for a flick response in the rat tail,
      which characterized development of secondary hyperalgesia. In addition, formalin
      induced secondary hyperalgesia was locally prevented by pre-but not post
      celecoxib treatment. However, celecoxib administered spinally inhibited formalin
      induced secondary hyperalgesia, either administered previously or following
      formalin. In contrast, piroxicam, an unspecific COX inhibitor which displays an
      increased selectivity towards COX-1, only prevented secondary hyperalgesia to
      formalin at a high dose following spinal administration. Taken together, these
      results suggest that COX-2 plays an important role both in the central and in the
      peripheral nerve sensitization following formalin administration in rat paws.
      They also suggested that once central sensitization starts it can no longer be
      blocked by a specific COX-2 inhibitor administered locally. Notwithstanding,
      spinal administration of a specific COX-2 inhibitor still blocks ongoing
      sensitization and prevents maintenance of central sensitization.

PMID- 15464833
TI  - The effect of various liposome formulations on insulin penetration across Caco-2
      cell monolayer.
AB  - The aim of the study was to determine the penetration properties of various
      insulin containing liposome formulations through Caco-2 cell monolayer and to
      compare the in vitro test results with in vivo tests. The effect of sodium
      taurocholate as a penetration enhancer when it was added to the liposome
      formulation was also investigated. In vitro permeation experiments were performed
      in diffusion cells with the Caco-2 cell monolayer used as the membrane.
      Permeability values of various insulin containing liposome formulations through
      Caco-2 cells were determined (log k(insulin-solution) = -2.217 +/- 0.0723 cm.h(
      1), log k(insulin-liposome) = -2.141 +/- 0.0625 cm.h(-1), log k(insulin-sodium
      tauroholate liposome)= -1.952 +/- 0.0623 cm.h(-1)). In vivo tests were performed
      in mice. Formulations were administered orally and blood glucose levels were
      determined and penetrations were compared with the Caco-2 cell experiment
      results. In conclusion, the permeability of insulin was increased across Caco-2
      cell monolayer when the liposome sodium taurocholate (NaTC) formulation was used.
      The oral administration of insulin and NaTC incorporated liposomes significantly
      decreased blood glucose levels. Furthermore, it was shown that a high in vitro/in
      vivo correlation was observed using the Caco-2 cell monolayer model.

PMID- 15464834
TI  - G2/M cell cycle arrest and induction of apoptosis by a stilbenoid, 3,4,5
      trimethoxy-4'-bromo-cis-stilbene, in human lung cancer cells.
AB  - Stilbenoids, including resveratrol (3,5,4'-trihydroxy-trans-stilbene) which is a
      naturally occurring phytoalexin abundant in grapes and several plants, have been
      shown to be active in inhibiting proliferation and inducing apoptosis in human
      cancer cell lines. Using resveratrol as the prototype, we have synthesized
      various analogs and evaluated their growth inhibitory effects in cultured human
      cancer cells. In the present study, we show that one of the stilbenoids, 3,4,5
      trimethoxy-4'-bromo-cis-stilbene (BCS), was more effective than its corresponding
      trans-isomer and resveratrol on the inhibition of cancer cell growth. Prompted by
      the strong growth inhibitory activity of BCS (IC50; 0.03 microM) compared to its
      trans-isomer (IC50; 6.36 microM) and resveratrol (IC50; 33.0 microM) in cultured
      human lung cancer cells (A549), we investigated its mechanism of action. BCS
      induced arrest at the G2/M phase cell cycle in the early time and subsequently
      increased in the sub-G1 phase DNA contents in a time-dependent manner, indicating
      induction of apoptosis. Morphological observation with round-up shape and DNA
      fragmentation was also revealed the apoptotic phenomena. BCS treatment elevated
      the expression levels of the pro-apoptotic protein p53, the cyclin-dependent
      kinase inhibitor p21, and the release of cytochrome c in the cytosol. The down
      regulation of checkpoint protein cyclin B1 by BCS was well correlated with the
      cell cycle arrest at G2/M. These data suggest the potential of BCS to serve as a
      cancer chemotherapeutic or chemopreventive agent by virtue of arresting the cell
      cycle and induction of apoptosis of human lung cancer cells.

PMID- 15464835
TI  - Hyperforin depletes synaptic vesicles content and induces compartmental
      redistribution of nerve ending monoamines.
AB  - Hyperforin, a phloroglucinol derivative found in Hypericum perforatum (St. John's
      wort) extracts has antidepressant properties in depressed patients. Hyperforin
      has a unique pharmacological profile and it inhibits uptake of biogenic
      monoamines as well as amino acid transmitters. We have recently showed that the
      monoamines uptake inhibition exerted by hyperforin is related to its ability to
      dissipate the pH gradient across the synaptic vesicle membrane thereby
      interfering with vesicular monoamines storage. In the present study we
      demonstrate that hyperforin induces dose-dependent efflux of preloaded [3H]5HT
      and [3H]DA from rat brain slices. Moreover, we show that hyperforin attenuates
      depolarization- dependent release of monoamines, while increasing monoamine
      release by amphetamine or fenfluramine. It is also demonstrated that
      preincubation of brain slices with reserpine is associated with dose- dependent
      blunting of efflux due to hyperforin. Our data indicate that hyperforin-induced
      efflux of [3H]5HT and [3H]DA reflect elevated cytoplasmic concentrations of the
      two monoamines secondary to the depletion of the synaptic vesicle content and the
      compartmental redistribution of nerve ending monoamines.

PMID- 15464836
TI  - Specific packaging of APOBEC3G into HIV-1 virions is mediated by the nucleocapsid
      domain of the gag polyprotein precursor.
AB  - In cells infected by HIV-1 mutants lacking a functional Vif protein, APOBEC3G is
      specifically packaged into progeny virions and then interferes with the process
      of virus infection. Here, we show that incorporation of APOBEC3G into HIV-1
      virions is mediated by the specific interaction of APOBEC3G with the carboxy
      terminal nucleocapsid/p6 domain of the Gag polyprotein precursor. As a result,
      HIV-1 virus-like particles that lack the nucleocapsid domain fail to package
      APOBEC3G. Surprisingly, RNA was also found to be essential for formation of the
      nucleocapsid--APOBEC3G complex in vitro, thus raising the possibility that RNA
      may form a bridge between these two proteins.

PMID- 15464837
TI  - The genome sequence analysis of H5N1 avian influenza A virus isolated from the
      outbreak among poultry populations in Thailand.
AB  - In this report, the genome of the Thai avian influenza virus A (H5N1);
      A/Chicken/Nakorn-Pathom/Thailand/CU-K2/04, isolated from the Thai avian influenza
      A (AI) epidemic during the early of 2004 was sequenced. Phylogenetic analyses
      were performed in comparison to AI viruses from Hong Kong 1997 outbreaks and
      other AI (H5N1) isolates reported during 2001-2004. Molecular characterization of
      the Thai AI (H5N1) HA gene revealed a common characteristic of a highly
      pathogenic AI (HPAI), a 20-codon deletion in the neuraminidase gene, a 5-codon
      deletion in the NS gene and polymorphisms of the M2 and PB2 genes. Moreover, the
      HA and NA genes of the Thai AI displayed high similarity to those of the AI
      viruses isolated from human cases during the same epidemic. Finally, our results
      demonstrated that the Thai AI emerged as a member of 2000's AI lineage with most
      of the genetic sequences closely related to the Influenza A/Duck/China/E319.2/03
      (H5N1).

PMID- 15464838
TI  - A C-terminal basic amino acid motif of Zaire ebolavirus VP35 is essential for
      type I interferon antagonism and displays high identity with the RNA-binding
      domain of another interferon antagonist, the NS1 protein of influenza A virus.
AB  - The ebolavirus VP35 protein antagonizes the cellular type I interferon response
      by blocking phosphorylation of IRF-3, a transcription factor that turns on the
      expression of a large number of antiviral genes. To identify the domain of VP35
      responsible for interferon antagonism, we generated mutations within the VP35
      gene and found that a C-terminal basic amino acid motif is required for
      inhibition of ISG56 reporter gene expression as well as IFN-beta production.
      Remarkably, this basic amino acid motif displayed high sequence identity with
      part of the N-terminal RNA-binding domain of another interferon-antagonist, the
      NS1 protein of influenza A virus.

PMID- 15464839
TI  - Potato virus X TGBp1 induces plasmodesmata gating and moves between cells in
      several host species whereas CP moves only in N. benthamiana leaves.
AB  - Experiments were conducted to compare the plasmodesmal transport activities of
      Potato virus X (PVX) TGBp1 and coat protein (CP) in several plant species.
      Microinjection experiments indicated that TGBp1 gates plasmodesmata in Nicotiana
      tabacum leaves. These results support previous microinjection studies indicating
      that TGBp1 gates plasmodesmata in Nicotiana benthamiana and Nicotiana clevelandii
      leaves. To study protein movement, plasmids expressing the green fluorescent
      protein (GFP) gene fused to the PVX TGBp1 or CP genes were biolistically
      bombarded to leaves taken from four different PVX host species. GFP/TGBp1 moved
      between adjacent cells in N. tabacum, N. clevelandii, N. benthamiana, and
      Lycopersicon esculentum, whereas GFP/CP moved only in N. benthamiana leaves.
      Mutations m12 and m13 were introduced into the TGBp1 gene and both mutations
      eliminated TGBp1 ATPase active site motifs, inhibited PVX movement, reduced
      GFP/TGBp1 cell-to-cell movement in N. benthamiana leaves, and eliminated
      GFP/TGBp1 movement in N. tabacum, N. clevelandii, and L. esculentum leaves.
      GFP/TGBp1m13 formed aggregates in tobacco cells. The ability of GFP/CP and mutant
      GFP/TGBp1 fusion proteins to move in N. benthamiana and not in the other PVX host
      species suggests that N. benthamiana plants have a unique ability to promote
      protein intercellular movement.

PMID- 15464840
TI  - Human hematopoietic (CD34+) stem cells possess high-affinity receptors for
      adenovirus type 11p.
AB  - Gene transfer into human hematopoietic stem cells using Ad5 is inefficient due to
      lack of the primary receptor CAR and the secondary receptors alphavbeta3 integrin
      and alphavbeta5 integrin, and due to the high seroprevalence of Ad5 antibodies in
      most adults, resulting in diminished gene transduction. In the present study, we
      screened six species (species A-F) of adenovirus, displaying different tropisms
      for interaction with CD34+ cells, at the level of virus attachment and
      expression. Virus particles were biotinylated and their binding capacity was
      determined by FACS analysis using streptavidin-FITC. Ad11p, Ad35, and Ad3
      (species B) showed high binding affinity, while Ad7, Ad11a (species B), and Ad37
      (species D) displayed intermediate affinity. Virions of Ad4 (species E), Ad5
      (species C), Ad31 (species A), and Ad41 (species F) hardly bound to hematopoietic
      progenitor cells. Using a double-labeling system, we demonstrated that
      adenoviruses bind to quiescent CD34+ cells. Ad11p virions showed the highest
      affinity among the adenoviruses detected. We further confirmed that virus fiber
      specific receptors were present on the hematopoietic progenitor cell surface,
      because both recombinant fiber of Ad11p and specific antiserum against rfiber
      could block virus attachment. The ability of the adenoviruses to infect
      hematopoietic cells was studied by immunofluorescence staining. The adenoviruses
      from species B and Ad37 showed higher infectivity than Ad31, Ad5, Ad4, and Ad41.
      Among the studied species B adenoviruses, Ad11p manifested a superior
      infectivity. Thus, we have confirmed that these cells have high-affinity
      receptors for species B:2 human adenovirus, Ad11p, and this virus may be used as
      candidate vector to target therapeutic genes to hematopoietic stem cells.

PMID- 15464841
TI  - The RNA helicase, nucleotide 5'-triphosphatase, and RNA 5'-triphosphatase
      activities of Dengue virus protein NS3 are Mg2+-dependent and require a
      functional Walker B motif in the helicase catalytic core.
AB  - The nonstructural protein 3 (NS3) of Dengue virus (DV) is a multifunctional
      enzyme carrying activities involved in viral RNA replication and capping:
      helicase, nucleoside 5'-triphosphatase (NTPase), and RNA 5'-triphosphatase
      (RTPase). Here, a 54-kDa C-terminal domain of NS3 (DeltaNS3) bearing all three
      activities was expressed as a recombinant protein. Structure-based sequence
      analysis in comparison with Hepatitis C virus (HCV) helicase indicates the
      presence of a HCV-helicase-like catalytic core domain in the N-terminal part of
      DeltaNS3, whereas the C-terminal part seems to be different. In this report, we
      show that the RTPase activity of DeltaNS3 is Mg2+-dependent as are both helicase
      and NTPase activities. Mutational analysis shows that the RTPase activity
      requires an intact NTPase/helicase Walker B motif in the helicase core,
      consistent with the fact that such motifs are involved in the coordination of
      Mg2+. The R513A substitution in the C-terminal domain of DeltaNS3 abrogates
      helicase activity and strongly diminishes RTPase activity, indicating that both
      activities are functionally coupled. DV RTPase seems to belong to a new class of
      Mg2+-dependent RTPases, which use the active center of the helicase/NTPase
      catalytic core in conjunction with elements in the C-terminal domain.

PMID- 15464842
TI  - BZLF1, an Epstein-Barr virus immediate-early protein, induces p65 nuclear
      translocation while inhibiting p65 transcriptional function.
AB  - We have previously demonstrated that the Epstein-Barr virus immediate-early BZLF1
      protein interacts with, and is inhibited by, the NF-kappaB family member p65.
      However, the effects of BZLF1 on NF-kappaB activity have not been intensively
      studied. Here we show that BZLF1 inhibits p65-dependent gene expression. BZLF1
      inhibited the ability of IL-1, as well as transfected p65, to activate the
      expression of two different NF-kappaB-responsive genes, ICAM-1 and IkappaB-alpha.
      BZLF1 also reduced the constitutive level of IkappaB-alpha protein in HeLa and
      A549 cells, and increased the amount of nuclear NF-kappaB to a similar extent as
      tumor necrosis factor-alpha (TNF-alpha) treatment. In spite of this BZLF1
      associated increase in the nuclear form of NF-kappaB, BZLF1 did not induce
      binding of NF-kappaB to NF-kappaB responsive promoters (as determined by
      chromatin immunoprecipitation assay) in vivo, although TNF-alpha treatment
      induced NF-kappaB binding as expected. Overexpression of p65 dramatically
      inhibited the lytic replication cycle of EBV in 293-EBV cells, confirming that NF
      kappaB also inhibits BZLF1 transcriptional function. Our results are consistent
      with a model in which BZLF1 inhibits the transcriptional function of p65,
      resulting in decreased transcription of IkappaB-alpha, decreased expression of
      IkappaB-alpha protein, and subsequent translocation of NF-kappaB to the nucleus.
      This nuclear translocation of NF-kappaB may promote viral latency by negatively
      regulating BZLF1 transcriptional activity. In situations where p65 activity is
      limiting in comparison to BZLF1, the ability of BZLF1 to inhibit p65
      transcriptional function may protect the virus from the host immune system during
      the lytic form of infection.

PMID- 15464843
TI  - HPV-18 confers resistance to TNF-alpha in organotypic cultures of human
      keratinocytes.
AB  - The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) inhibits
      normal keratinocytes proliferation. However, many human papillomavirus (HPV)
      immortalized or transformed cell lines are resistant to TNF-alpha
      antiproliferative effect. The present study analyzes the effects of TNF-alpha on
      organotypic cultures of primary human keratinocytes (PHKs) that express HPV-18
      oncogenes. Raft cultures prepared with PHKs acutely transfected with HPV-18 whole
      genome or infected with recombinant retroviruses containing only E6/E7 or E7 were
      treated with 2 nM TNF-alpha. While BrdU incorporation into basal/parabasal cells
      of normal PHKs cultures was markedly inhibited by TNF-alpha cultures transfected
      with HPV-18 whole genome showed proliferation in all cell strata. Furthermore,
      BrdU incorporation into cultures expressing E6/E7 or E7 was not significantly
      reduced, indicating that E7 alone confers partial resistance to TNF-alpha.
      Besides, TNF-alpha treatment did not alter p16ink4a, p21cip1, p27kip1, or cyclin
      E levels, but did reduce cyclin A and PCNA levels in sensitive cells.

PMID- 15464844
TI  - Identification of syncytial mutations in a clinical isolate of herpes simplex
      virus 2.
AB  - Small polykaryocytes resulting from cell fusion are found in herpes simplex virus
      (HSV) lesions in patients, but their significance for viral spread and
      pathogenesis is unclear. Although syncytial variants causing extensive fusion in
      tissue culture can be readily isolated from laboratory strains, they are rarely
      found in clinical isolates, suggesting that extensive cell fusion may be
      deleterious in vivo. Syncytial mutations have previously been identified for
      several laboratory strains, but not for clinical isolates of HSV type 2. To
      address this deficiency, we studied a recent syncytial clinical isolate, finding
      it to be a mixture of two syncytial and one nonsyncytial strain. The two
      syncytial strains have novel mutations in glycoprotein B, and in vitro cell
      fusion assays confirmed that they are responsible for syncytium formation. This
      panel of clinical strains may be ideal for examining the effect of increased cell
      fusion on pathogenesis.

PMID- 15464845
TI  - The vaccinia virus B1R kinase induces p53 downregulation by an Mdm2-dependent
      mechanism.
AB  - Poxvirus infection has a strong effect on cellular functions. To understand viral
      pathogenesis, it is necessary to know how viral proteins interact with host
      proteins. The B1R kinase is an early viral gene required for vaccinia virus DNA
      synthesis and replication, but no cellular substrate is known for this viral
      kinase. B1R is able to hyperphosphorylate p53 in several residues in the N
      terminal transactivation domain, including Ser15 and Thr18. B1R does not
      phosphorylate Mdm2. B1R promotes an increase in p53 ubiquitination and a
      reduction of p53 acetylation by p300. The over-expressed B1R protein induces the
      degradation of p53 in a concentration-dependent manner and is lost when Ser15 and
      Th18 are changed to alanine or when the B1R kinase is inactivated by introducing
      the K149Q substitution. The B1R-induced downregulation of p53 requires Mdm2. The
      hyperphosphorylated p53 is transcriptionally active, and this activity also falls
      as B1R increases. The BAX gene promoter is more sensitive to this reduction of
      transcription than p21 or 14-3-3 gene promoters. This effect of B1R on p53 can be
      one of the mechanisms by which vaccinia virus exerts its role in infected cells.

PMID- 15464846
TI  - Enhanced mucosal and systemic immunogenicity of human papillomavirus-like
      particles encapsidating interleukin-2 gene adjuvant.
AB  - Here, we report the enhanced mucosal and systemic immunogenicity of human
      papillomavirus type (HPV) 16 L1 virus-like particles (VLP) encapsidating a
      cytokine genetic adjuvant. Plasmid DNA expressing interleukin-2 (pIL2) was
      encapsidated in VLP using the reassembly property of VLP from disassembled L1
      capsomeres. pIL2 in reassembled VLP showed stability against DNase I, indicating
      encapsidation. After intramuscular immunization into mice, the highest vaginal
      and salivary HPV16 L1-specific IgA titers were observed in pIL2-encapsidated VLP,
      followed by VLP plus pIL2 in separate plasmid, and VLP alone. Similar to mucosal
      responses, serum IgG, IgG1, and IgG2a antibody titers were the highest in the
      group treated with pIL2-encapsidated VLP. Moreover, the adjuvanticity of pIL2
      encapsidated in VLP was stronger in IgG2a antibody relative to IgG1 antibody. Our
      results indicate that the encapsidation of a genetic cytokine adjuvant pIL2 would
      be beneficial for more effective induction of mucosal and systemic immune
      responses to VLP vaccines.

PMID- 15464847
TI  - Comparison of immune responses against foot-and-mouth disease virus induced by
      fusion proteins using the swine IgG heavy chain constant region or beta
      galactosidase as a carrier of immunogenic epitopes.
AB  - Previously, we demonstrated that a fusion protein (Gal-FMDV) consisting of beta
      galactosidase and an immunogenic peptide, amino acids (141-160)-(21-40)-(141
      160), of foot-and-mouth disease virus (FMDV) VP1 protein induced protective
      immune responses in guinea pigs and swine. We now designed a new potential
      recombinant protein vaccine against FMDV in swine. The immunogenic peptide, amino
      acids (141-160)-(21-40)-(141-160) from the VP1 protein of serotype O FMDV, was
      fused to the carboxy terminus of a swine immunoglobulin G single heavy chain
      constant region and expressed in Escherichia coli. The expressed fusion protein
      (IgG-FMDV) was purified and emulsified with oil adjuvant. Vaccination twice at an
      interval of 3 weeks with the emulsified IgG-FMDV fusion protein induced an FMDV
      specific spleen proliferative T-cell response in guinea pigs and elicited high
      levels of neutralizing antibody in guinea pigs and swine. All of the immunized
      animals were efficiently protected against FMDV challenge. There was no
      significant difference between IgG-FMDV and Gal-FMDV in eliciting immunity after
      vaccination twice in swine. However, when evaluating the efficacy of a single
      inoculation of the fusion proteins, we found that IgG-FMDV could elicit a
      protective immune response in swine, while Gal-FMDV only elicited a weak
      neutralizing activity and could not protect the swine against FMDV challenge. Our
      results suggest that the IgG-FMDV fusion protein is a promising vaccine candidate
      for FMD in swine.

PMID- 15464848
TI  - Role for a region of helically unstable DNA within the Epstein-Barr virus latent
      cycle origin of DNA replication oriP in origin function.
AB  - The minimal replicator of the Epstein-Barr virus (EBV) latent cycle origin of DNA
      replication oriP is composed of two binding sites for the Epstein-Barr virus
      nuclear antigen-1 (EBNA-1) and flanking inverted repeats that bind the telomere
      repeat binding factor TRF2. Although not required for minimal replicator
      activity, additional binding sites for EBNA-1 and TRF2 and one or more auxiliary
      elements located to the right of the EBNA-1/TRF2 sites are required for the
      efficient replication of oriP plasmids. Another region of oriP that is predicted
      to be destabilized by DNA supercoiling is shown here to be an important
      functional component of oriP. The ability of DNA fragments of unrelated sequence
      and possessing supercoiled-induced DNA duplex destabilized (SIDD) structures, but
      not fragments characterized by helically stable DNA, to substitute for this
      component of oriP demonstrates a role for the SIDD region in the initiation of
      oriP-plasmid DNA replication.

PMID- 15464849
TI  - DNA vaccines expressing soluble CD4-envelope proteins fused to C3d elicit cross
      reactive neutralizing antibodies to HIV-1.
AB  - DNA vaccines expressing the envelope (Env) of the human immunodeficiency virus
      type 1 (HIV-1) have been relatively ineffective at generating high-titer, long
      lasting, neutralizing antibodies in a variety of animal models. In this study,
      DNA vaccines were constructed to express a fusion protein of the soluble human
      CD4 (sCD4) and the gp120 subunit of the HIV-1 envelope. To enhance the
      immunogenicity of the expressed fusion protein, three copies of the murine C3d
      (mC3d3) were added to the carboxyl terminus of the complex. Monoclonal antibodies
      that recognize CD4-induced epitopes on gp120 efficiently bound to sCD4-gp120 or
      sCD4-gp120-mC3d3. In addition, both sCD4-gp120 and sCD4-gp120-mC3d3 bound to
      cells expressing appropriate coreceptors in the absence of cell surface hCD4.
      Mice (BALB/c) vaccinated with DNA vaccines expressing either gp120-mC3d3 or sCD4
      gp120-mC3d3 elicited antibodies that neutralized homologous virus infection.
      However, the use of sCD4-gp120-mC3d3-DNA elicited the highest titers of
      neutralizing antibodies that persisted after depletion of anti-hCD4 antibodies.
      Interestingly, only mice vaccinated with DNA expressing sCD4-gp120-mC3d3 had
      antibodies that elicited cross-protective neutralizing antibodies. The fusion of
      sCD4 to the HIV-1 envelope exposes neutralizing epitopes that elicit broad
      protective immunity when the fusion complex is coupled with the molecular
      adjuvant, C3d.

PMID- 15464850
TI  - Complete genome analysis and molecular characterization of Usutu virus that
      emerged in Austria in 2001: comparison with the South African strain SAAR-1776
      and other flaviviruses.
AB  - Here we describe the complete genome sequences of two strains of Usutu virus
      (USUV), a mosquito-borne member of the genus Flavivirus in the Japanese
      encephalitis virus (JEV) serogroup. USUV was detected in Austria in 2001 causing
      a high mortality rate in blackbirds; the reference strain (SAAR-1776) was
      isolated in 1958 from mosquitoes in South Africa and has never been associated
      with avian mortality. The Austrian and South African isolates exhibited 97%
      nucleotide and 99% amino acid identity. Phylogenetic trees were constructed
      displaying the genetic relationships of USUV with other members of the genus
      Flavivirus. When comparing USUV with other JEV serogroup viruses, the closest
      lineage was Murray Valley encephalitis virus (nt: 73%, aa: 82%) followed by JEV
      (nt: 71%, aa: 81%) and West Nile virus (nt: 68%, aa: 75%). Comparison of the
      genomes showed that the conserved structural elements and putative enzyme motifs
      were homologous in the two USUV strains and the JEV serogroup. The factors that
      determine the severe clinical symptoms caused by the Austrian USUV strain in
      Eurasian blackbirds are discussed. We also offer a possible explanation for the
      origins and dispersal of USUV, JEV, and MVEV out of Africa.

PMID- 15464851
TI  - Multihormonal control of vitellogenesis in lower vertebrates.
AB  - The comparative approach on how and when vitellogenesis occurs in the diverse
      reproductive strategies displayed by aquatic and terrestrial lower vertebrates is
      presented in this chapter; moreover, attention has been paid to the multihormonal
      control of hepatic vitellogenin synthesis as it is related to seasonal changes
      and to vitellogenin use by growing oocytes. The hormonal mechanisms regulating
      vitellogenin synthesis are also considered, and the effects of environmental
      estrogens on the feminization process in wildlife and humans have been reported.
      It is then considered how fundamental nonmammalian models appear to be, for
      vitellogenesis research, addressed to clarifying the yolkless egg and the
      evolution of eutherian viviparity.

PMID- 15464852
TI  - Structure, evolutionary conservation, and functions of angiotensin- and
      endothelin-converting enzymes.
AB  - Angiotensin-converting enzyme, a member of the M2 metalloprotease family, and
      endothelin-converting enzyme, a member of the M13 family, are key components in
      the regulation of blood pressure and electrolyte balance in mammals. From this
      point of view, they serve as important drug targets. Recently, the involvement of
      these enzymes in the development of Alzheimer's disease was discovered. The
      existence of homologs of these enzymes in invertebrates indicates that these
      enzyme systems are highly conserved during evolution. Most invertebrates lack a
      closed circulatory system, which excludes the need for blood pressure regulators.
      Therefore, these organisms represent excellent targets for gaining new insights
      and revealing additional physiological roles of these important enzymes. This
      chapter reviews the structural and functional aspects of ACE and ECE and will
      particularly focus on these enzyme homologues in invertebrates.

PMID- 15464853
TI  - Cell and molecular biology of nucleolar assembly and disassembly.
AB  - Nucleoli disassemble in prophase of the metazoan mitotic cycle, and they begin
      their reassembly (nucleologenesis) in late anaphase?early telophase. Nucleolar
      disassembly and reassembly were obvious to the early cytologists of the
      eighteenth and nineteenth centuries, and although this has lead to a plethora of
      literature describing these events, our understanding of the molecular mechanisms
      regulating nucleolar assembly and disassembly has expanded immensely just within
      the last 10-15 years. We briefly survey the findings of nineteenth-century
      cytologists on nucleolar assembly and disassembly, followed by the work of Heitz
      and McClintock on nucleolar organizers. A primer review of nucleolar structure
      and functions precedes detailed descriptions of modern molecular and microscopic
      studies of nucleolar assembly and disassembly. Nucleologenesis is concurrent with
      the reinitiation of rDNA transcription in telophase. The perichromosomal sheath,
      prenucleolar bodies, and nucleolar-derived foci serve as repositories for
      nucleolar processing components used in the previous interphase. Disassembly of
      the perichromosomal sheath along with the dynamic movements and compositional
      changes of the prenucleolar bodies and nucleolus-derived foci coincide with
      reactivation of rDNA synthesis within the chromosomal nucleolar organizers during
      telophase. Nucleologenesis is considered in various model organisms to provide
      breadth to our understanding. Nucleolar disassembly occurs at the onset of
      mitosis primarily as a result of the mitosis-specific phosphorylation of Pol I
      transcription factors and processing components. Although we have learned much
      regarding nucleolar assembly and disassembly, many questions still remain, and
      these questions are as vibrant for us today as early questions were for
      nineteenth- and early twentieth-century cytologists.

PMID- 15464854
TI  - MAPping the eukaryotic tree of life: structure, function, and evolution of the
      MAP215/Dis1 family of microtubule-associated proteins.
AB  - The MAP215/Dis1 family of proteins is an evolutionarily ancient family of
      microtubule-associated proteins, with characterized members in all major kingdoms
      of eukaryotes, including fungi (Stu2 in S. cerevisiae, Dis1 and Alp14 in S.
      pombe), Dictyostelium (DdCP224), plants (Mor1 in A. thaliana and TMBP200 in N.
      tabaccum), and animals (Zyg9 in C. elegans, Msps in Drosophila, XMAP215 in
      Xenopus, and ch-TOG in humans). All MAP215/Dis1 proteins (with the exception of
      those in plants) localize to microtubule-organizing centers (MTOCs), including
      spindle pole bodies in yeast and centrosomes in animals, and all bind to
      microtubules in vitro and?or in vivo. Diverse roles in regulating microtubule
      assembly and organization have been proposed for individual family members, and a
      substantial body of evidence suggests that MAP215/Dis1-related proteins play
      critical roles in the assembly and function of the meiotic/mitotic spindles
      and/or cell division. An extensive search of public databases (including both EST
      and genome databases) identified partial sequences predicted to encode more than
      three dozen new members of the MAP215/Dis1 family, including putative MAP215/Dis1
      related proteins in Giardia lamblia and four other protists, sixteen additional
      species of fungi, six plants, and twelve animals. The structure and function of
      MAP215/Dis1 proteins are discussed in relation to the evolution of this ancient
      family of microtubule-associated proteins.

PMID- 15464855
TI  - The supramedullary neurons of fish: present status and goals for the future.
AB  - In this paper, we report the recent findings on supramedullary neurons of fish,
      with special attention to the studies, which made the nature of this neuronal
      system clear. Indeed, immunohistochemical, physiological and neuroanatomical
      data, taken together, point out that this neuronal system is a component of the
      autonomic nervous system. New goals have been opened by the more recent research,
      especially in comparative neurobiology. Indeed, the supramedullary neurons, owing
      to some characteristics, like the DNA endoreplication, the large size, the
      accessible localization and the relationship with glial cells, may be utilised as
      a very suitable model in several fields of neurobiology of vertebrates, such as
      molecular genetic, electrophysiology, nervous system ageing, glial-neuron
      interactions.

PMID- 15464856
TI  - Rat estrous cycle influences the sexual diergism of HPA axis stimulation by
      nicotine.
AB  - We previously reported that female rats had significantly greater hypothalamic
      pituitary-adrenal (HPA) axis responses to cholinergic stimulation by nicotine
      (NIC) than did male rats. Females in defined estrous cycle stages, however, were
      not studied because of sample size limitations. We further explored this finding
      by determining HPA axis responses to two doses of NIC in female rats (N = 101)
      during different estrous cycle stages, and in males (N = 69). NIC doses were: 0.3
      mg/kg, which provided the greatest female-male difference in the earlier study,
      and 0.5 mg/kg, which stimulated the HPA axis similarly in the two sexes. Plasma
      AVP, ACTH, and corticosterone were measured. Proestrous and estrous females had
      higher ACTH responses to NIC (0.3 mg/kg) compared to metestrous and diestrous
      females, and compared to males. ACTH responses to NIC (0.5 mg/kg) were similar,
      regardless of estrous cycle stage or sex. Males had higher AVP responses to both
      NIC doses compared to females in all estrous cycle stages. Corticosterone
      responses followed the ACTH responses, except that females in all estrous stages
      started from a higher corticosterone baseline compared to males. These results
      are similar to our earlier findings across the estrous cycle with non-specific
      cholinergic stimulation by physostigmine and suggest that the nicotinic system
      contributes to the differential HPA axis responses to cholinergic challenge
      across the estrous cycle.

PMID- 15464857
TI  - Diurnal variation in the genital reflexes and hormone levels induced by
      paradoxical sleep deprivation and cocaine in male rats.
AB  - The purpose was to ascertain whether the genital reflexes induced by paradoxical
      sleep deprivation (PSD) in male rats show diurnal variation, and whether the
      hormonal rhythm of testosterone and progesterone is involved in these behaviors.
      Genital reflexes (penile erection -- PE, and ejaculation -- EJ) and hormone
      levels were assessed during a 24 h period at four testing times (0900, 1600, 2100
      and 0400 h) in PSD rats injected with saline or cocaine. Results indicated that
      PE in PSD rats given saline or cocaine did not show diurnal variation while EJ
      responses were significantly reduced at 0400 h in the PSD-cocaine group. The home
      cage control group testosterone concentrations were lower at 1600, 2100 and 0400
      h than at 0900 h. At 0900 h, testosterone levels were significantly lower in the
      PSD groups than in the control group. In contrast, progesterone levels were
      significantly higher in PSD groups in relation to the control group at the four
      testing times. Thus, we observed strong diurnal variation in testosterone and
      progesterone in control rats whereas only EJ responses in PSD-cocaine seemed to
      be influenced by the time of day. These results suggest that progesterone may
      influence the modulation of male genital reflexes displayed by sleep-deprived
      rats.

PMID- 15464858
TI  - Effect of a high-salt diet on gamma-aminobutyric acid-mediated responses in the
      nucleus tractus solitarius of Sprague-Dawley rats.
AB  - Previous study using an indirect gamma-aminobutyric acid (GABA) agonist indicated
      that high salt intake enhances sensitivity of nucleus tractus solitarius (NTS)
      projecting inhibitory input to rostral ventrolateral medulla sympathoexcitatory
      neurons. We further investigated the relationship between salt intake and the
      GABA system in NTS. Sprague-Dawley (S-D) rats consuming high dietary salt (8%) or
      low dietary salt (0.3%) for 3 weeks were used. Under chloralose-anesthesia,
      baseline arterial pressure (AP) and heart rate (HR) were similar in both groups.
      Bilateral injection into NTS of nipecotic acid, GABA(A) receptor agonist
      (muscimol), or GABA(B) receptor agonist (baclofen) elicited greater pressor
      responses in high-salt group. GABA(A) receptor antagonist, bicuculline and
      GABA(B) receptor antagonist, CGP-35348 elicited greater depressor responses.
      Phenylephrine or nitroprusside (i.v.) elicited similar respective increases or
      decreases in AP in both groups. Baroreflex sensitivity was similar. Thus, high
      salt intake enhances both GABA(A) receptor- and GABA(B) receptor-mediated
      responses within NTS, thereby inhibiting elevation of AP.

PMID- 15464859
TI  - Alpha7 nicotinic acetylcholine receptors targeted by cholinergic developmental
      neurotoxicants: nicotine and chlorpyrifos.
AB  - Alpha7 nicotinic acetylcholine receptors (nAChRs) play a role in axonogenesis,
      synaptogenesis and synaptic plasticity, and are therefore potential targets for
      developmental neurotoxicants. We administered nicotine to neonatal rats during
      discrete periods spanning the onset and peak of axonogenesis/synaptogenesis,
      focusing on three brain regions with disparate distributions of cell bodies and
      neural projections: brainstem, forebrain and cerebellum. Nicotine treatment on
      postnatal days (PN) 1-4 had little or no effect on alpha7 nAChRs but treatment
      during the second (PN11-14) or third (PN21-24) weeks elicited significant
      decrements in receptor expression in brainstem and cerebellum, regions containing
      cell bodies that project to the forebrain. Exposure to chlorpyrifos, a
      neurotoxicant pesticide that acts partially through cholinergic mechanisms, also
      elicited deficits in alpha7 nAChRs during the second postnatal week but not the
      first week. For both nicotine and chlorpyrifos, the effects on alpha7 nAChRs were
      distinct from those on the alpha4beta2 subtype. Continuous prenatal nicotine
      exposure, which elicits subsequent, postnatal deficits in axonogenesis and
      synaptogenesis, also produced delayed-onset changes in alpha7 nAChRs,
      characterized by reductions in the forebrain and upregulation in the brainstem
      and cerebellum, a pattern consistent with impaired axonogenesis/synaptogenesis
      and reactive sprouting. Males were more sensitive to the persistent effects of
      prenatal nicotine exposure on alpha7 nAChRs, a pattern that mimics
      neurobehavioral deficits resulting from this treatment. The present findings
      reinforce the mechanistic involvement of alpha7 nAChRs in the actions of
      developmental neurotoxicants, and its biomarker potential for neuroteratogens
      that target neuritic outgrowth.

PMID- 15464861
TI  - CPP and amlodipine alter the decrease in basal acetylcholine and choline release
      by audiogenic stimulus in hippocampus of ethanol-withdrawn rats in vivo.
AB  - Effects of N-methyl-D-aspartate (NMDA) receptor and Ca2+ channel antagonists on
      extracellular acetylcholine and choline release in the hippocampus of ethanol
      withdrawn rats were investigated by in vivo microdialysis. Ethanol was
      administered to Wistar rats in a liquid diet for 28 days. Basal acetylcholine and
      choline levels significantly increased at the 24th hour of ethanol withdrawal
      syndrome (EWS). Either an NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4
      yl)-propyl-1-phosphonic acid (CPP) or a calcium channel antagonist amlodipine was
      administered, and 15 min later, an audiogenic stimulus (100 dB, 1 min) was
      applied to rats. While audiogenic stimulus increased acetylcholine and had no
      effect on choline release in control rats, it decreased acetylcholine and
      increased choline release in ethanol-withdrawn rats. CPP (15 mg/kg) and
      amlodipine (20 mg/kg) reversed the decrement in acetylcholine and increment in
      choline release in EW rats. Their effects on acetylcholine and choline release
      were not different from saline in control rats. Therefore, our findings suggest
      that, (a) because of adaptive changes in EWS, decrease of the acetylcholine
      release following audiogenic stimulus may play a role in the triggering of
      seizures, (b) hippocampal glutamatergic pathway may play a role in the audiogenic
      stimulus induced decrement of acetylcholine release in EWS, (c) inhibition of
      this pathway by NMDA receptor and calcium channel antagonists may prevent
      triggering of the seizures.

PMID- 15464860
TI  - Biochemical brain markers and purinergic parameters in rat CSF after seizure
      induced by pentylenetetrazol.
AB  - Cellular and molecular mechanisms involved in the generation of seizures and the
      magnitude of neural cells injury are not fully understood. We evaluated astrocyte
      and/or neuronal injury in rats in the pentylenetetrazol model of acute seizures
      by measuring S100B and NSE levels in cerebrospinal fluid. Additionally, we
      determined ADP and GDP hydrolysis by soluble nucleoside triphosphate
      diphosphohydrolase in the cerebrospinal fluid, and the concentration of
      nucleosides adenosine, inosine and guanosine as putative markers of brain injury.
      After pentylenetetrazol-induced seizures: (i) S100B values increased from 10 to
      30 min, returning to control levels at 24 h; NSE levels presented a biphasic
      increase: an increase at 10 to 30 min returning to control levels, and again at
      240 min followed by a decline at 24 h; (ii) nucleotidase activities increased
      from 10 min, returning to control levels at 240 min; (iii) guanosine and inosine
      levels increased exclusively after 30 min. In summary, this study showed
      biochemical changes in the cerebrospinal fluid occurring after seizures induced
      by pentylenetetrazol. Such events may have a modulating effect upon seizure
      expression, particularly nucleoside triphosphate diphosphohydrolase activities
      and nucleoside concentrations, but are nevertheless followed by neural death as
      evidenced by the increase in NSE and S100B levels.

PMID- 15464862
TI  - Characterization of hemizygous SOD1/wild-type transgenic mice with the SHIRPA
      primary screen and tests of sensorimotor function and anxiety.
AB  - SOD1 is one of several overexpressed genes in Down's syndrome. In order to
      dissect genetic causes of the syndrome, hemizygous human wild-type SOD1
      transgenic mice were compared to FVB/N non-transgenic controls at 3 months of age
      in the SHIRPA primary screen of neurologic function as well as in tests of motor
      activity and coordination. The responsiveness of SOD1/wt transgenic mice to
      visual and somatosensory stimuli was reduced in placing, pinna, corneal, and toe
      pinch tests. In addition, SOD1/wt transgenic mice crossed fewer segments on a
      stationary beam. On the contrary, there was no intergroup difference for motor
      activity and anxiety in open-field and emergence tests and for latencies before
      falling on the stationary beam, coat-hanger, and rotorod. These results indicate
      mild deficits in sensorimotor responsiveness in a mouse model expressing human
      SOD1 and that the overexpressed gene may be responsible for some Down symptoms.

PMID- 15464863
TI  - Long-term follow-up study with repetitive transcranial magnetic stimulation
      (rTMS) in Parkinson's disease.
AB  - Several studies have claimed the effectiveness of repetitive transcranial
      magnetic stimulation (rTMS) in Parkinson's disease (PD). The rTMS therapy has to
      be repeated regularly to achieve a permanent effect but the side effects of long
      term administration of low frequency rTMS are not known. Further, there is no
      information about its influence on the development of Parkinson's disease. Two
      different groups of patients with PD were compared in a retrospective study for 3
      years. The first group (A) was treated with drugs, the second group (B) was
      treated with drugs + rTMS (1 Hz, 0.6 T, 100 stimuli per day for 7 days using a
      round coil). rTMS was repeated at least twice each year for 3 years. Symptoms of
      PD were assessed using the Graded Rating Scale. Although at the onset of the
      study group B patients had greater disease severity and were receiving higher
      doses of levodopa, this group (receiving rTMS) showed no deterioration in these
      parameters, whereas those in group A receiving drugs alone showed a marked
      deterioration. Hoehn-Yahr (H-Y) stages at the onset of the study and 3 years
      later were: group A: 1.93 +/- 0.75, 3.03 +/- 1.01; group B: 2.50 +/- 0.83, 2.45
      +/- 0.62. The dose of levodopa (mg/day) was at the onset of trial and 3 years
      later was: group A: 124.4 +/- 144.0, 555.5 +/- 247.2; group B: 287.7 +/- 217.1,
      333.4 +/- 181.0. The yearly increment in the scores was: group A: 1.308 +/- 0.307
      (P < 0.001), group B: 0.642 +/- 0.389 (P < 0.1). Accordingly, this retrospective
      study using regularly repeated rTMS with 1 Hz for 7 days, at least twice yearly
      for 3 years, significantly slowed the development of Parkinson's disease.
      Unwanted side effects were not observed during the 3 years.

PMID- 15464864
TI  - Responses of primary vestibular neurons to galvanic vestibular stimulation (GVS)
      in the anaesthetised guinea pig.
AB  - Previous studies in humans and animals which have shown that DC galvanic
      vestibular stimulation (GVS) induces horizontal and torsional eye movements have
      been interpreted as being due to a preferential activation of primary vestibular
      afferents innervating the horizontal semicircular canals and otoliths by GVS. The
      present study sought to determine in guinea pigs whether GVS does indeed
      selectively activate primary horizontal canal and otolith afferents. Constant
      current GVS was passed between electrodes implanted in the tensor-tympani muscle
      of each middle ear or between electrodes on the skin over the mastoid. During
      this stimulation, responses from single primary vestibular neurons were recorded
      extracellularly by glass microelectrodes in Scarpa's ganglion. Afferents from all
      vestibular sensory regions were activated by both surface and tensor-tympani
      galvanic stimulation. Tensor tympani GVS was approximately 10 times more
      effective than surface GVS. At larger current intensities irregularly discharging
      afferents showed an asymmetrical response: cathodal stimulation resulted in a
      larger change in firing (increase) than anodal stimulation (decrease), whereas
      regularly discharging afferents responded symmetrically to the two polarities of
      GVS. Across all afferents tuned for different types of natural vestibular
      stimulation, neuronal sensitivity for GVS was found to increase with discharge
      variability (as indexed by CV*). Anterior canal afferents showed a slightly
      higher sensitivity than afferents from other vestibular sensory regions. Hence,
      the present study concluded that GVS activates primary vestibular afferents
      innervating all sensory regions in a uniform fashion. Therefore, the specific
      pattern of GVS-induced eye movements reported in previous studies are not due to
      differential sensitivity between different vestibular sensory regions, but are
      likely to reflect an involvement of central processing.

PMID- 15464865
TI  - Suppressive effect of Saiko-ka-ryukotsu-borei-to, a herbal medicine, on excessive
      release of glutamate in the hippocampus.
AB  - Glutamate is the major excitatory neurotransmitter in the brain, and the excess
      of glutamate concentration in the synaptic cleft is a cause of neuronal injury or
      death. To find out a drug suppressing the excess of extracellular glutamate
      concentration, the effect of Saiko-ka-ryukotsu-borei-to, a herbal medicine, was
      examined in the control and zinc-deficient rats, a neurological disease model, by
      using in vivo microdialysis. The excessive increase in extracellular glutamate in
      the hippocampus was induced by perfusion with 100 mM KCl for 40 min.
      Administration of Saiko-ka-ryukotsu-borei-to did not appreciably influence the
      increase in body weight of the control rats and the retarded increase in body
      weight of zinc-deficient rats. However, administration of Saiko-ka-ryukotsu-borei
      to to the control rats completely suppressed the increase in glutamate
      concentration in the hippocampal extracellular fluid during stimulation with high
      K+. The suppressive effect of Saiko-ka-ryukotsu-borei-to was also observed in
      zinc-deficient rats, in which extracellular glutamate concentration was markedly
      increased during stimulation with high K+. These results suggest that Saiko-ka
      ryukotsu-borei-to is a useful drug for prevention or cure of excitotoxicity of
      glutamate.

PMID- 15464866
TI  - Effects of NMDA glutamate receptor antagonist drugs on the volitional consumption
      of ethanol by a genetic drinking rat.
AB  - The ability of drugs that reduce NMDA receptor activity on the volitional
      consumption of ethanol in the genetic drinking rat, mHEP line, was investigated.
      After the consumption of ethanol solutions and water by each male or female mHEP
      rat had stabilized on its preferred concentration, different doses of LY 274614,
      a competitive NMDA antagonist, MK 801, a non-competitive NMDA antagonist, (+)-HA
      966 or ACPC (1-aminocyclopropane-1-carboxylic acid), antagonists of the glycine
      site were administered daily for three days. The dose of 3.0 mg/kg i.p. LY 274614
      reduced the consumption of ethanol by 64% compared to the pre-treatment baseline,
      while 0.3 mg/kg of MK 801 reduced consumption by 44%, 20 mg/kg (+)-HA-966 reduced
      consumption by 47% and 300 mg/kg of ACPC reduced consumption by 30%. These doses
      of LY 274614 and MK 801 reduced the ability of Sprague-Dawley rats to walk on a
      rotorod. Effects of these drugs on food intake were small except for the 20 mg/kg
      dose of (+)-HA-966. Therefore, the drugs did not have an anti-caloric effect and
      manipulations of the glutamatergic system through NMDA receptors may modify the
      consumption of ethanol. This interaction should be explored further for its
      therapeutic potential and to better understand the control by central neuronal
      systems of the consumption of ethanol.

PMID- 15464867
TI  - New polymers for drug delivery systems in orthopaedics: in vivo biocompatibility
      evaluation.
AB  - The use of biodegradable polymers for drug delivery systems excluded the need for
      a second operation to remove the carrier. However, the development of an
      avascular fibrous capsule, reducing drug release, has raised concern about these
      polymers in terms of tissue-implant reaction. Five novel polymers were evaluated
      in vivo after implantation in the rat dorsal subcutis and compared to the
      reference polycaprolactone (PCL). Poly(cyclohexyl-sebacate) (PCS), poly(L-lactide
      b-1,5-dioxepan-2-one-b-L-lactide) (PLLA-PDXO-PLLA), two 3-hydroxybutyrate-co-3
      hydroxyvalerate copolymers (D400G and D600G), and a poly(organo)phosphazene (POS
      PheOEt:Imidazole) specimens were histologically evaluated in terms of the
      inflammatory tissue thickness and vascular density at 4 and 12 weeks from
      surgery. The highest values of inflammatory tissue thickness were observed in
      D600G (P < 0.01), PCS (P < 0.001) and PLLA-PDXO-PLLA (P < 0.001) at 4 weeks,
      while POP-PheOEt:Imidazole showed the lowest value of inflammatory tissue
      thickness (P < 0.05) at 12 weeks. D400G, D600G, PLLA-PDXO-PPLA and POP
      PheOEt:Imidazole showed higher (P < 0.001) values of vascular density near the
      implants in comparison to PCL at 4 weeks. Finally, D400G and D600G increased
      their vessel densities while POP-PheOEt:Imidazole and the synthetic polyester
      PLLA-PDXO-PLLA presented similar vessel density values during experimental times.
      These different behaviours to improve neoangiogenesis without severe inflammatory
      tissue-responses could be further investigated with drugs in order to obtain time
      programmable drug delivery systems for musculoskeletal therapy.

PMID- 15464868
TI  - Adsorption of cationic antibacterial on collagen-coated titanium implant devices.
AB  - Two different cationic antimicrobial molecules, chlorhexidine (CH) and
      poly(hexamethylenebiguanide) (PH), were adsorbed from aqueous solution to
      titanium implant devices surface-modified by the covalent coupling of collagen on
      a polyanionic acrylic acid overlayer. Results show that more antimicrobial was
      adsorbed on surface modified implants as compared to control titanium devices.
      Moreover, the kinetic of release was affected by the interaction between the
      polyanionic overlayer and the cationic antimicrobial, leading to slower kinetic
      of release in the case of CH and stable adsorption in the case of polycationic PH
      . These data indicate that biochemically modified collagen coated surfaces could
      be endowed also by antimicrobial properties, in the spirit of present researches
      on multifunctional implant surfaces.

PMID- 15464869
TI  - An in vitro study of the peroxyl and hydroxyl radical scavenging capacity of the
      calcium antagonist amlodipine.
AB  - Amlodipine has been reported to improve endothelial function in patients with
      arterial hypertension and to significantly limit the progression of carotid
      atherosclerosis. The aim of this study was to assess the total antioxidant
      activity of amlodipine. We measured the in vitro antioxidant activity of
      amlodipine as its ability to antagonize the oxidation of alpha-keto-gamma
      methiolbutyric acid by both hydroxyl and peroxyl radicals. The results are
      expressed as Total Oxyradical Scavenging Capacity (TOSC) units. Reduced
      glutathione, uric acid and trolox were used as the reference antioxidants.
      Amlodipine showed an efficiency as scavenger of peroxyl radicals (TOSC: 5945 +/-
      544 units/mg) significantly higher (>50%, P <0.001) than that of GSH (2733 +/-
      636 units/mg), and 70% lower (P < 0.0001) than the value obtained with uric acid
      (18144 +/- 696 units/mg) and trolox (17522 +/- 734 units/mg). Of interest, the
      scavenging capacity of amlodipine towards hydroxyl radicals (1455 +/- 154
      units/mg) was 320% higher (P < 0.00001) than that of GSH (358 +/- 112 units/mg),
      20% higher than that of uric acid (1198 +/- 121 units/mg), and 100% higher than
      that of trolox (759 +/- 143 units/mg). Amlodipine has intrinsic antioxidant
      activity with both anti-hydroxyl and anti-peroxyl radicals activity.

PMID- 15464870
TI  - Skin microcirculation in peripheral arterial obliterative disease.
AB  - The important role of microcirculation in the pathophysiology and symptoms of
      peripheral arterial obliterative disease (PAOD) has been progressively emphasized
      during the past twenty years, thanks to the use of different non-invasive
      methods, such as capillaroscopy, laser Doppler (LD) fluxmetry and transcutaneous
      measurement of oxygen tension (tcPO2). Basally, in the diseased leg of stage II
      PAOD patients, leg skin perfusion recorded by means of LD fluxmetry is
      quantitatively normal. However, spectral analysis of skin LD tracing shows an
      abnormal flowmotion, with increased amplitude of the flowmotion waves related to
      endothelial, neurogenic and myogenic activities, suggesting a relatively early
      skin microcirculatory adaptation in this PAOD stage. Following ischemia, an
      impaired total skin LD hyperemia and a reduced skin capillary nutritional blood
      flow at capillaroscopy, concomitantly with a reduced increase of flowmotion waves
      related to endothelial, myogenic and sympathetic activities, have been observed
      in the diseased leg of stage II PAOD patients. In critical limb ischemia (CLI), a
      more advanced cutaneous microcirculatory deterioration has been clarified, with a
      more severely impaired post-ischemic hyperemia, a reduced tcPO2 and a severely
      perturbed skin flowmotion in the diseased leg. This integrated skin
      microcirculatory diagnostic approach can be used for a better management of PAOD
      patients.

PMID- 15464871
TI  - Plasma antioxidant activity and cutaneous microvascular endothelial function in
      athletes and sedentary controls.
AB  - Aging is associated with endothelial dysfunction in both conduit arteries and
      peripheral microcirculation. Furthermore, aging is associated with an increased
      susceptibility to free radical mediated tissue damage. The aim of this study was
      to assess the relationship between age, regular aerobic-endurance training,
      plasma antioxidant activity and microcirculatory skin blood flow in healthy
      individuals. Thirty-six male athletes (range: 22-74 years; VO2max 54.3 +/- 5.2
      ml/kg/min) and 36 age-sex-matched sedentary controls (range: 20-75 years; VO2max
      34.2 +/- 3.4 ml/kg/min) were studied. Each group was divided into a younger (<30
      years) and an older (>60 years) subgroup. Hand and foot baseline and stimulated
      skin blood flow (SBF) was measured by laser-Doppler flowmetry. Plasma free
      radicals antioxidant capacity against both peroxyl and hydroxyl radicals was also
      evaluated as Total Oxyradical Scavenging Capacity (TOSC) units. Baseline SBFs
      were not significantly different between athletes and sedentary groups, while
      plasma TOSC values against peroxyl radicals (18.4 +/- 3.1 vs. 13.8.0 +/- 3.4
      units/ml, P < 0.001) and hydroxyl radicals (8.7 +/- 2.5 vs 4.9 +/- 2.3 units/ml,
      P <0.001) was higher in athletes. Hand SBF after heating and ischemia and foot
      SBF after heating were higher in athletes (P <0.0001) than in the sedentary
      group. In the sedentary groups, the lowest tertile of age had higher plasma TOSC
      values than the highest tertile of age (ROO- 18.2 +/- 2.2 vs 8.8 +/- 1.4
      units/ml; HO- 9.2 +/- 1.3 vs 3.7 +/- 0.5 units/ml, P < 0.001). Among athletes,
      the lowest and the highest tertile of age did not show significantly different
      plasma TOSC (young: ROO- 20.3 +/- 1.5 and HO-: 9.7 +/- 1.4 units/ml; older: ROO-:
      17.1 +/- 1.3 and HO-: 9.0 +/- 0.8 units/ml, n.s.). Resting SBF was similar in all
      the subgroups; stimulated SBFs were lower in both subgroups of untrained respect
      to trained individuals (P <0.001). In the sedentary subjects, SBF was inversely
      related to age (r = -0.63; P <0.0001) and directly related to TOSC against
      peroxyl (r = 0.59, P <0.001) and hydroxyl radicals (r = 0.47, P <0.01). In
      athletes SBF was related only to VO2max (r = 0.36; P <0.05) and TOSC vs ROO. (r =
      0.41, P <0.01). In conclusion, these results suggest that regular physical
      activity is associated with a better microvascular endothelial function in older
      athletes probably due to increased antioxidant defenses.

PMID- 15464872
TI  - Left ventricular diastolic function and carotid artery wall in elderly athletes
      and sedentary controls.
AB  - Advancing age is characterized by structural and functional change of left
      ventricle (LV) and large elastic arteries. Recent advances in tissue Doppler
      imaging (TDI) and integrated backscatter (IBS), new ultrasound tools, have
      allowed non-invasive assessment of structural and functional characterization of
      myocardium and artery wall. Our aim was to compare LV diastolic function and
      carotid artery remodeling in elderly athletes and sedentary controls. Twenty-five
      elderly athletes (males, aged 68.6 +/- 4.2 years) were compared to 25 age-sex
      matched sedentary controls. All the subjects underwent either conventional
      Doppler echocardiography with pulsed TDI to evaluate LV diastolic function, and
      conventional ultrasonography and integrated backscatter (IBS) analysis to
      evaluate the carotid wall. Corrected IBS values (C-IBS) were obtained by
      subtracting the IBS value of the adventitia. Body mass index and blood pressure
      were not different in the two groups; athletes showed lower heart rate (P <
      0.0001) and, as expected, higher LV mass than sedentary subjects (P < 0.0001).
      Transmitral Doppler analysis showed in trained subjects a significantly lower
      peak A and a higher E/A ratio (P < 0.001). On regards to TDI measurements,
      athletes exhibited a higher Em, a lower Am, and, subsequently, an increased Em/Am
      ratio of both lateral wall and septum (P < 0.0001). The IVRTm was shorter in
      trained subjects (P < 0.001). Athletes showed a lower C-IBS (-26.8 +/- 2.9 vs. 
      23.4 +/- 3.8 dB, P < 0.001) and a smaller intima-media thickness (IMT: 0.66 +/-
      0.14 vs. 0.80 +/- 0.18 mm, P < 0.001) respect to sedentary controls. Moreover, a
      significant direct correlation was found between Em/Am of LV septal and lateral
      wall and C-IBS values (respectively, r = 0.62 and r = 0.56, P < 0.001). Thus the
      aging heart manifests structural and functional changes in response to physical
      activity. The expected pattern of cardiac and arterial alterations normally seen
      in response to age is modified in the older athletes, suggesting the exercise
      training is an effective stimulus in shaping arterial structure and left
      ventricular function in older heart. It would appear that pulsed TDI and IBS
      analysis may play an important role in detecting training-induced LV and carotid
      artery structural and functional modifications.

PMID- 15464873
TI  - Responses to Tilt test in young and elderly patients with syncope of unknown
      origin.
AB  - The aim of the present study was to assess the cardiovascular autonomic function
      and responses to tilt test in young and elderly patients with syncope of unknown
      origin. We evaluated two groups of patients with previous unexplained syncope:
      192 older subjects (112 males, 80 females, mean age 67.2 +/- 6.8 years) and 188
      young subjects (102 males, 86 females, mean age 25 +/- 9 years). All patients
      underwent ambulatory electrocardiogram (ECG) monitoring, to evaluate time domain
      indices of heart rate variability (HRV), and head-up tilt test in the morning
      after an overnight fast. The responses of positive tilt test were classified
      using the VAsovagal Syncope International Study (VASIS) criteria: mixed (VASIS
      1), cardioinhibition (VASIS-2A), severe cardioinhibition/asystole (VASIS-2B),
      pure vasodepression (VASIS-3). All the time-domain HRV indexes were lower in the
      older than in young subjects. The rate of positive responses was not different in
      the two groups. In elderly group the positive head-up tilt test responses showed:
      a pure vasodepressive response (VASIS 3) in 126 patients (65%), a mixed (VASIS-1)
      response in 25 patients (13%), a cardioinhibitory (VASIS-2A) response in 13
      patients (7%). Only 28 (14.6%) of elderly group patients had negative head-up
      tilt test response. In contrast, in young group the positive head-up tilt test
      responses showed: 114 patients (61.2%) a mixed (VASIS-1) vasovagal response, 40
      patients (22.3%) a cardioinhibitory (VASIS-2A) response, four (2.1%) patients a
      severe cardioinhibitory (VASIS-2B) and four (2.1%) patients a pure vasodepression
      (VASIS-3) response, respectively. The tilt test was negative in response in 26
      young patients (12.2%). Our results confirm that the head-up tilt test may be
      useful in assessing unexplained syncope, since it is seen to be positive in 85%
      of elderly patients and 86% in young patients. In our subjects, vasodepressive
      response was the most frequent cause of syncope in older subjects, while
      vasovagal response is the commonest cause of syncope of young patients. This
      different behaviour in the elderly may be is explained with physiological aging,
      which is associated with a reduction of sympathetic-parasympathetic control on
      the cardiac rhythm, demonstrated by reduction in all the time domain HRV indices.

PMID- 15464874
TI  - Oral low-dose cyclophosphamide in metastatic hormone refractory prostate cancer
      (MHRPC).
AB  - The chemotherapeutic approach to hormone-refractory metastatic prostate cancer
      (MHRPC) for a long time included only estramustine. Then, attempts have been made
      with other various agents as cyclophosphamide, vinblastine, etoposide, taxanes
      and carboplatinum. Although the new drugs and combinations have increased the
      response rate of MHRPC, they have had no impact on the natural history of MHRPC,
      which is about 1 year as median time of survival. After an occasional observation
      of prolonged response in a patient with MHRPC treated with a very well tolerated
      oral low-dose of cyclophosphamide, from February 1996 to October 2002, seven more
      patients with MHRPC and progressive disease were consecutively recruited.
      Response to treatment was evaluated by conventional radiological procedures
      and/or serial serum PSA measurements. The decline of PSA value was considered to
      assess the response consistent with the response guidelines from the prostate
      specific antigen-working group. All eight studied patients continuously received
      oral low dose cyclophosphamide until progression or the occurrence of significant
      toxicity. So far three patients (37.5%) progressed (PD), two (25%) showed PR and
      the three remaining SD. Response rate was 25%, and clinical benefit occurred in
      62.5% of the studied patients. In the five patients with clinical benefit on
      cyclophosphamide median duration of clinical benefit, PR and SD were 9, 24+ and 8
      months, respectively. In these five patients median overall survival times from
      cyclophosphamide and from the first regimen of chemotherapy were 17 and 33+
      months respectively, while in the three patients with PD they were 4 and 13
      months. The same interval times in patients with > or =50% decline of serum PSA
      were 29 and 50.5 months, while in those with <50% decline of the same marker,
      they were 13 and 32 months, respectively. Grade 2 or 3 neutropenia were observed
      in all the studied patients. In four (50%) of them pulmonary and urinary
      infections that were easily cured by the common antibiotics occurred. These data
      suggest that the metronomic use of cyclophosphamide, given alone, has similar or
      higher activity with lower toxicity than when administered with other active
      drugs. So it can be an useful option before or after the use of other single or
      combined potentially active chemotherapeutic agents.

PMID- 15464875
TI  - Restaging after neoadjuvant chemoradiotherapy for rectal adenocarcinoma: role of
      F18-FDG PET.
AB  - Multimodality treatment of loco-regional advanced rectal cancer has demonstrated
      to improve local control and overall survival. Proctoscopy, digital rectal
      examination (DRE), computer tomography (CT), endorectal ultrasound (ERUS), and
      magnetic resonance imaging (MRI) cannot correctly detect downstaging in rectal
      tumors after chemo radiation therapy (CRT). New imaging techniques, like 18F-FDG
      PET, may play some role in predicting the pathologic response to CRT before
      surgical resection. Aim of the present study was to further investigate the
      accuracy and predictive value of 18F-FDG PET in a large series of patients with
      rectal cancer treated with preoperative intensified CRT. Between January 2000 and
      December 2003, 81 patients with histologically proven adenocarcinoma in clinical
      stage II-III disease, according to criteria of TNM classification, were included
      in this study. All patients were submitted to diagnostic staging workup with DRE,
      proctoscopy with biopsy, ERUS, CT scan of the abdomen and pelvis or pelvic MRI
      plus liver ultrasonography, coloscopy or barium colonic enema. One month later
      the end of CRT all patients were submitted to diagnostic restaging work-up (DRW)
      and 18F-FDG PET. Surgery was performed 8-9 weeks after the end of CRT and
      pathologic stage was defined. Moreover a pathologic assessment of tumor
      regression was made with tumor regression grade score (TRG). PET correctly
      identified 22/28 (79% specificity) patients with complete pathologic response
      (pCR). However, sensitivity was 45% (24/53) while PPV, and NPV were equal to 77
      and 43%, respectively. Total PET accuracy rate was 56%. PET sensitivity increased
      from 45 to 56% if the end-point was pCR, or TRG score, respectively. The best
      correlation was found between PET findings and pathologic stage (P <0.01) or TRG
      score (P <0.01). The accurate identification of rectal cancer patients with major
      pathological response after preoperative CRT further supports the necessity of
      designing prospective studies with new and more accurate was imaging technologies
      with the main object of offering conservative treatment in responder patients.

PMID- 15464876
TI  - Defining a new annotation object for DICOM image: a practical approach.
AB  - In this article, we present a new way of creating annotation objects for DICOM
      images, using the redundant data channel. Various types of annotations, including
      types containing color information, are possible and annotation objects can
      overlap the original DICOM image on a screen. Annotation objects can be created
      easily using a digital pen. Scanned images used in an electronic patient record
      can be added to objects. Although there are various ways of manipulating
      annotation objects, such as insertion, addition and modification of annotation
      objects in the DICOM image, the original clinical image is not affected because a
      redundant data channel is used for the annotation. The proposed method is
      expected to be very useful to medium and small clinics that cannot afford picture
      archiving and communication systems, as the DICOM standard makes provision for
      the annotation of clinical images in various ways.

PMID- 15464877
TI  - 3D long bone reconstruction based on level sets.
AB  - In medical imaging a three-dimensional (3D) object must often be reconstructed
      from serial cross-sections to aid in the comprehension of the object's structure
      as well as to facilitate its automatic manipulation and analysis. The most
      popular interpolation scheme for a sequence of image slices is the shape-based
      method, where object information extracted from a given 3D volume image is used
      in guiding the interpolation process. The paper presents a level set
      reformulation of the well-known shape-based method as well as a new automatic
      level set method, which offers better performance. In particular, we focus on X
      ray examinations of long bones, which also requires us to deal with the problem
      of an optimal slice positioning. To this aim, a 2D version of the proposed
      algorithm will be used to localize a subset of slices from the entire volume
      image. A number of experiments were performed on computed tomographic real images
      to evaluate the proposed approach. The experimental results show a substantial
      improvement of visual effects (qualitative evaluation) using the proposed method
      in comparison to both the conventional gray-level interpolation scheme and the
      shape-based method. Compared with the shape-based interpolation scheme the
      proposed method has much lower computational cost.

PMID- 15464878
TI  - Digital subtraction CT angiography based on efficient 3D registration and
      refinement.
AB  - A novel method for fast, automatic 3D digital subtraction CT angiography (DS-CTA)
      is presented to generate artifact-free angiograms. The proposed method consists
      of two steps: 3D registration to align a CT image to the CT angiography (CTA)
      image and subtraction-and-refinement to extract blood vessels only. For efficient
      and accurate 3D registration in the first step, an normalized mutual information
      (NMI) based algorithm is adopted, and its fast version is developed by
      introducing a new measure. To further improve the subtracted image quality in the
      second step, a novel 3D refinement algorithm is suggested to effectively remove
      unwanted residuals. Experimental results of seven clinical CT/CTA head datasets
      demonstrate that cerebral vessels are well extracted from CTA images with almost
      no loss. The typical processing time is 3-9 min depending on the image size in a
      PC with a 2.4 GHz CPU.

PMID- 15464879
TI  - Image processing for craniofacial landmark identification and measurement: a
      review of photogrammetry and cephalometry.
AB  - Facial surface anthropometry and cephalometry have been used for many years for
      the diagnosis of malformations, surgical planning and evaluation, and growth
      studies. These disciplines rely on the identification of craniofacial landmarks.
      Methods for 3D reconstruction of landmarks have been introduced, as have image
      processing algorithms for the automation of landmark extraction. This paper
      reviews facial surface anthropometry and cephalometry with reference to the image
      processing algorithms that have been applied and their effectiveness.

PMID- 15464880
TI  - Computerised planning of the acquisition of cardiac MR images.
AB  - A method to automatically plan acquisition of magnetic resonance images aligned
      with the cardiac axes is presented. Localiser images are acquired with a mean
      short axis orientation calculated from a group of (n=50) adult patients. These
      images are segmented using the expectation maximization algorithm. The borders of
      the ventricular blood pools are found and used to provide an estimate of the
      orientation of the cardiac axes. These estimated orientations are compared with
      corresponding manually aligned orientations. The method has been tested on n=12
      volunteers showing an error of within 12 degrees which is sufficiently accurate
      for clinical use.

PMID- 15464881
TI  - Modeling the growth plates in the pediatric knee: implications for anterior
      cruciate ligament reconstruction.
AB  - The authors develop 3-D models of the pediatric knee from magnetic resonance
      imaging (MRI) image files, with the goal of minimizing injury to the pediatric
      growth plate during surgery. Computerized tomography (CT) scans have better
      resolution and contrast between bone and soft tissue than MRI scans; however,
      surgeons rely upon MRI scans to plan knee-joint surgeries such as anterior
      cruciate ligament (ACL) reconstruction. Surgeons can use the virtual models to
      plan and verify surgical procedures such as hole drilling and ligament
      attachments, and to determine volume removed from a growth plate due to different
      drill-hole placements with various drill sizes.

PMID- 15464882
TI  - Imaging diagnosis of congenital uterine malformation.
AB  - Congenital anomaly of the female reproductive system is associated with higher
      rate of infertility, spontaneous abortion, intrauterine growth retardation,
      premature birth and postpartum bleed. Because of the variable clinical pictures
      of obstruction of menstrual flow in adolescence to hypomenorrhea, vaginal
      discharge, dyspareunia, and fertility problems in adult life, early and accurate
      diagnosis is difficult. Complete uterine and vaginal septum can be easily
      confused with uterus didelphys. Management of these two mullerian duct anomalies
      is different. With improved treatment methods for complete relief of symptoms and
      prevention of further sequelae, comprehensive evaluation is important to identify
      the underlying problem and formulate appropriate therapeutic plan. The
      embryology, classification, and clinical presentation of uterine malformation,
      advantages and limitations of diagnostic methods including hysterosalpingogram,
      ultrasound, magnetic resonance imaging, laparoscopy, and hysteroscopy are
      discussed. The imaging features of different types of uterine anomalies are
      illustrated.

PMID- 15464884
TI  - Regulation of exocytosis in neurons and neuroendocrine cells.
AB  - Neurons communicate with one another through the release of molecules from
      synaptic vesicles and large dense core granules through the process of
      exocytosis. During exocytosis, molecules are released to the extracellular space
      through a fusion pore, which can either dilate, resulting in full fusion, or
      close, resulting in incomplete exocytosis, often referred to as 'kiss and run'
      exocytosis. Recently, there has been much interest in the regulation of this
      process in both neurons and neuroendocrine cells. There has been much recent work
      that addresses the existence of incomplete exocytosis in neurons and
      neuroendocrine cells, as well as recent work probing the molecular components and
      modulation of the fusion pore.

PMID- 15464885
TI  - Ephaptic interactions within a chemical synapse: hemichannel-mediated ephaptic
      inhibition in the retina.
AB  - The two best-known types of cell-cell communication are chemical synapses and
      electrical synapses, which are formed by gap junctions. A third, less well known,
      form of communication is ephaptic transmission, in which electric fields
      generated by a specific neuron alter the excitability of neighboring neurons as a
      result of their anatomical and electrical proximity. Ephaptic communication can
      be present in a variety of forms, each with their specific features and
      functional implications. One of these is ephaptic modulation within a chemical
      synapse. This type of communication has recently been proposed for the cone
      horizontal cell synapse in the vertebrate retina. Evidence indicates that the
      extracellular potential in the synaptic terminal of photoreceptors is modulated
      by current flowing through connexin hemichannels at the tips of the horizontal
      cell dendrites, mediating negative feedback from horizontal cells to cones. This
      example can be added to the growing list of cases of ephaptic communication in
      the central nervous system.

PMID- 15464886
TI  - Spatial and temporal control of signaling through lipid rafts.
AB  - Sphingolipid- and cholesterol-dependent microdomains (rafts) order proteins at
      biological membranes and have been implicated in most signaling processes at the
      cell surface, but the principles and mechanisms through which lipid rafts
      influence signaling are not well understood. Recent studies have revealed how
      lipid rafts are rapidly redistributed and assembled locally in response to
      extracellular signals, and how components of raft-based signaling domains undergo
      rapid and regulated rearrangements influencing signal quality, duration, and
      strength. These findings highlight the exquisitely dynamic properties of
      signaling domains based on lipid rafts, and suggest that processes of raft
      trafficking and assembly take central roles in mediating spatial and temporal
      control of signaling.

PMID- 15464887
TI  - Intrinsic neuronal regulation of axon and dendrite growth.
AB  - Neurons extend long axons and highly branched dendrites, and our understanding of
      the essential regulators of these processes has advanced in recent years. In the
      past year, investigators have shown that transcriptional control,
      posttranslational degradation and signaling cascades may be master regulators of
      axon and dendrite elongation and branching. Thus, evidence is mounting for the
      importance of the intrinsic growth state of a neuron as a crucial determinant of
      its ability to grow, or to regenerate, axons and dendrites.

PMID- 15464888
TI  - Neurotrophin action on a rapid timescale.
AB  - Mechanisms underlying the fast action of neurotrophins include intracellular
      Ca(2+) signaling, neuronal excitation, augmentation of synaptic excitation by
      modulation of N-methyl-d-aspartate receptor activity and control of synaptic
      inhibition through the regulation of the K(+)-Cl(-) cotransporter KCC2. The
      fastest action of brain-derived neurotrophic factor and neurotrophin-4/5 occurs
      within milliseconds, and involves activation of TrkB and the opening of the Na(+)
      channel Na(v)1.9. Through these rapid actions, neurotrophins shape neuronal
      activity, modulate synaptic transmission and produce instructive signals for the
      induction of long-term changes in the efficacy of synaptic transmission.

PMID- 15464889
TI  - Molecular motors in neuronal development, intracellular transport and diseases.
AB  - Molecular motors such as kinesin superfamily proteins (KIFs), dynein superfamily
      proteins and myosin superfamily proteins have diverse and fundamental roles in
      many cellular processes, including neuronal development and the pathogenesis of
      neuronal diseases. During neuronal development, KIFs take significant roles in
      the regulation of axon-collateral branch extension, which is essential for brain
      wiring. Cytoplasmic dynein together with LIS1 takes pivotal roles in neocortical
      layer formation. In axons, anterograde transport is mediated by KIFs, whereas
      retrograde transport is mediated mainly by cytoplasmic dynein, and dysfunction of
      motors results in neurodegenerative diseases. In dendrites, the transport of NMDA
      and AMPA receptors is mediated by KIFs, and the motor has been shown to play a
      significant part in establishing learning and memory.

PMID- 15464890
TI  - Binding proteins for mRNA localization and local translation, and their
      dysfunction in genetic neurological disease.
AB  - Neurons utilize mRNA transport and local translation as a means to influence
      development and plasticity. The molecular mechanisms for this mRNA sorting
      involve the recognition of cis-acting sequences by distinct mRNA binding proteins
      that have a dual role, acting in both mRNA transport and translational
      regulation. Other proteins play a part in the assembly of messenger
      ribonucleoprotein complexes into transport granules. mRNA binding proteins are
      crucial targets of phosphorylation signals that regulate local translation.
      Fragile X syndrome and spinal muscular atrophy have emerged as two genetic
      neurological diseases that could result, in part, from impaired assembly,
      localization, and translational regulation of these messenger ribonucleoproteins.

PMID- 15464891
TI  - Amyloid-beta precursor protein processing in neurodegeneration.
AB  - The amyloid-beta precursor protein is proteolytically cleaved by secretases,
      resulting in a series of fragments, including the amyloid-beta peptide of
      Alzheimer's disease. The amyloid precursor protein, when membrane anchored, could
      operate as a receptor. After cleavage, the soluble ectodomain exerts a trophic
      function in the subventricular zone. The amyloid-beta peptide itself has a
      depressant role in synaptic transmission, with both physiological and
      pathological implications. During the past two years, much time has been invested
      in determining the molecular pathways that regulate the processing and the signal
      transduction of the amyloid precursor protein. However, the absence of consistent
      and informative phenotypes in different loss of function animal models make
      elucidating the molecular actions of the amyloid-beta precursor protein an
      ongoing challenge.

PMID- 15464893
TI  - Novel techniques in electron microscopy.
AB  - Emerging techniques in electron microscopy promise to yield a wide range of new
      information about the nervous system. Aided by the development of detectors,
      electron optics, energy filters, computer automation and preparative methods,
      electron tomography now provides three-dimensional structures over a scale
      ranging from single receptor molecules to synapses and neurons. To relate
      structure to function, a variety of correlative methods are being developed,
      including protein tags observable both by light microscopy of living cells and,
      subsequently, by electron microscopy. It is also becoming possible to measure
      functionally important ions like Ca(2+) in cellular compartments at a scale of
      about 10 nm by exploiting new advances in electron energy loss and X-ray
      spectroscopic imaging.

PMID- 15464894
TI  - Concepts for nanoscale resolution in fluorescence microscopy.
AB  - Spatio-temporal visualization of cellular structures by fluorescence microscopy
      has become indispensable in biology. However, the resolution of conventional
      fluorescence microscopy is limited by diffraction to about 180 nm in the focal
      plane and to about 500 nm along the optic axis. Recently, concepts have emerged
      that overcome the diffraction resolution barrier fundamentally. Formed on the
      basis of reversible saturable optical transitions, these concepts might
      eventually allow us to investigate hitherto inaccessible details within live
      cells.

PMID- 15464895
TI  - Nonlinear microscopy: new techniques and applications.
AB  - Nonlinear microscopy, a general term that embraces any microscopy technique based
      on nonlinear optics, is further establishing itself as an important tool in
      neurobiology. Recent advances in labels, labeling techniques, and the use of
      native or genetically encoded contrast agents have bolstered the capacity of
      nonlinear microscopes to image the structure and function of not just single
      cells but of entire networks of cells. Along with novel strategies to image over
      exceptionally long durations and with increased depth penetration in living
      brains, these advances are opening new opportunities in neurobiology that were
      previously unavailable.

PMID- 15464897
TI  - Biophysical models of fMRI responses.
AB  - Functional magnetic resonance imaging (fMRI) is used to investigate where the
      neural implementation of specific cognitive processes occurs. The standard
      approach uses linear convolution models that relate experimentally designed
      inputs, through a haemodynamic response function, to observed blood oxygen level
      dependent (BOLD) signals. Such models are, however, blind to the causal
      mechanisms that underlie observed BOLD responses. Recent developments have
      focused on how BOLD responses are generated and include biophysical input-state
      output models with neural and haemodynamic state equations and models of
      functional integration that explain local dynamics through interactions with
      remote areas. Forward models with parameters at the neural level, such as dynamic
      causal modelling, combine both approaches, modelling the whole causal chain from
      external stimuli, via induced neural dynamics, to observed BOLD responses.

PMID- 15464898
TI  - Fluorescent proteins as sensors for cellular functions.
AB  - The exploitation of green fluorescent protein-based biosensors promises to
      revolutionize functional imaging of the nervous system. Various approaches have
      created a multitude of reporters of neuronal activity and of activation of
      biochemical signaling pathways. Although the number of different probes has
      increased significantly, the critical step remains to bring these probes from the
      cuvette through the imaging of single cells to the imaging of whole organisms in
      vivo. The recent development of new genetically encoded sensors and their
      functional expression in model organisms are encouraging signs that the field is
      moving ahead in this direction.

PMID- 15464896
TI  - Fiber optic in vivo imaging in the mammalian nervous system.
AB  - The compact size, mechanical flexibility, and growing functionality of optical
      fiber and fiber optic devices are enabling several new modalities for imaging the
      mammalian nervous system in vivo. Fluorescence microendoscopy is a minimally
      invasive fiber modality that provides cellular resolution in deep brain areas.
      Diffuse optical tomography is a non-invasive modality that uses assemblies of
      fiber optic emitters and detectors on the cranium for volumetric imaging of brain
      activation. Optical coherence tomography is a sensitive interferometric imaging
      technique that can be implemented in a variety of fiber based formats and that
      might allow intrinsic optical detection of brain activity at a high resolution.
      Miniaturized fiber optic microscopy permits cellular level imaging in the brains
      of behaving animals. Together, these modalities will enable new uses of imaging
      in the intact nervous system for both research and clinical applications.

PMID- 15464899
TI  - Labeling neurons in vivo for morphological and functional studies.
AB  - Increasingly sophisticated strategies for labeling cells in vivo are providing
      unprecedented opportunities to study neurons in living animals. Transgenic
      expression of genetically encoded reporters enables us to monitor changes in
      neuronal activity in response to sensory stimuli, and the labeling of single
      neurons with fluorescent proteins allows the dynamics of neuronal connectivity to
      be observed in transgenic animals over periods ranging from minutes to months.
      Advances in transient labeling techniques such as viral infection and
      electroporation provide a rapid means by which to analyze neuronal gene function
      in vivo. These new approaches to labeling, manipulating and imaging neurons in
      intact organisms are transforming the way in which the nervous system is studied.

PMID- 15464900
TI  - Genetic mosaic analysis in the nervous system.
AB  - Genetic mosaic techniques provide a powerful tool for dissecting gene function in
      the intricate genetic networks that underlie the formation and function of
      nervous systems. For instance, it is possible to make individual cells or groups
      of cells homozygous for mutations of interest at specific points during an
      organism's development. It is also possible to resolve lineage relationships and
      to characterize cellular morphology and connectivity. Current techniques for
      creating genetically mosaic organisms incorporate improved controls over clone
      induction, identification, and/or mosaic tissue characterization.

PMID- 15464903
TI  - Kinase inhibitors in leukemia.

PMID- 15464901
TI  - Post-transcriptional gene silencing in neurons.
AB  - The techniques evolving from the rapidly developing field of small RNAs promise
      accessible approaches to dissecting cellular and molecular mechanisms of higher
      brain function. Here, a current overview of the technology is presented, along
      with an outline of how these approaches might help neuroscientists to more
      rapidly uncover the cellular and molecular bases of behavior.

PMID- 15464904
TI  - Therapy of acute promyelocytic leukemia.

PMID- 15464905
TI  - Investigational agents in myeloid disorders.

PMID- 15464906
TI  - Methodologic issues in investigation of targeted therapies in acute myeloid
      leukemia.

PMID- 15464907
TI  - Purine analogs in leukemia.

PMID- 15464908
TI  - Monoclonal antibody therapy in lymphoid leukemias.

PMID- 15464909
TI  - Native antibody and antibody-targeted chemotherapy for acute myeloid leukemia.

PMID- 15464910
TI  - Radioimmunotherapy of leukemia.

PMID- 15464911
TI  - Immunotoxins and toxin constructs in the treatment of leukemia and lymphoma.

PMID- 15464912
TI  - Antibody therapy of lymphoma.

PMID- 15464913
TI  - Vaccines in leukemia.

PMID- 15464914
TI  - Therapeutic idiotype vaccines for non-Hodgkin's lymphoma.

PMID- 15464915
TI  - Cytokine modulation of the innate immune system in the treatment of leukemia and
      lymphoma.

PMID- 15464916
TI  - Donor lymphocyte infusions.

PMID- 15464917
TI  - Somatic cell engineering and the immunotherapy of leukemias and lymphomas.

PMID- 15464918
TI  - Combination therapy with capecitabine and interferon alfa-2A in patients with
      advanced renal cell carcinoma: a phase II study.
AB  - Capecitabine is a fluoropyrimidine carbamate capable of exploiting the high
      concentrations of thymidine phosphorylase in tumor tissue to achieve activation
      preferentially at the tumor site. Thymidine phosphorylase activity is high in
      renal cell carcinoma tissue. Interferon alfa has been proved to be the agent for
      standard therapy in metastatic renal cell carcinoma. The purpose of the study was
      to assess the efficacy and toxicity of combining capecitabine and interferon alfa
      2A in patients with advanced renal cell carcinoma. Twenty-five patients with
      advanced renal cell carcinoma and no prior systemic therapy were treated with the
      combination of capecitabine at a dose of 1,250 mg/m2 twice daily for 2 weeks
      after every 21 days and interferon alfa-2A 6 million U three times a week. The
      overall response rate was 24.0% (95% CI, 9.4-45.1%), from 6 responded patients 5
      had partial responses and 1 complete response. Stable disease status was achieved
      in 9 patients (36.0% with 95% CI 18.0-57.5%). The median survival time was 248
      days (95% CI, 173-265 days). The median time to progression was 126 days (95% CI,
      49-165 days). Grade 3-4 toxicities occurred in 12 patients and included fatigue
      (33.3%), nausea, hand-foot syndrome (both 12.5%), anorexia (8.3%), vomiting,
      anemia and neutropenia (all 4.2%). The capecitabine and interferon alfa-2A
      combination has clinical activity and an acceptable toxicity profile in patients
      with metastatic renal cell carcinoma. The importance of adding capecitabine to
      interferon alfa needs to be confirmed in a randomized trial.

PMID- 15464919
TI  - A multi-institutional phase II trial of gemcitabine plus paclitaxel in patients
      with locally advanced or metastatic urothelial cancer.
AB  - The purpose of the study was to evaluate response and survival in patients with
      metastatic urothelial cancer treated with combination gemcitabine and paclitaxel
      administered on a biweekly schedule at doses of 3000 mg/m2 and 150 mg/m2,
      respectively. Patients with adequate organ function and performance status were
      accrued through 7 institutions, stratified by prior therapy status, and treated
      as noted. Response was evaluated by 1979 bi-dimensional World Health Organization
      (WHO) criteria. Of 55 eligible patients, 17 had a partial and 5 had a complete
      response rate for an overall response rate of 40% (27-54%). One complete response
      and one partial response were observed in the 6 previously treated patients.
      Overall median survival was 11.8 months (11.9 months in the chemonaive cohort).
      Grade 3 or 4 myelosuppression occurred in 56%, but only 4 serious infections were
      observed. We conclude that because of a lower than expected complete response
      rate, even when corrected for prognostic groupings, this regimen is not
      recommended for routine use in patients with metastatic urothelial cancer.
      Insufficient patients with poor renal function or prior therapy were accrued to
      reach conclusions regarding its utility in these subgroups.

PMID- 15464921
TI  - Surgical treatment for local control of female urethral carcinoma.
AB  - We reviewed 53 patients (mean age 63 years) who underwent partial urethrectomy (n
      = 26) or radical extirpation (n = 27) for primary female urethral cancer from
      1948 through 1999. Clinical stage, histology, high pathologic stage (3 or 4) and
      grade, tumor location, nodal status, surgery type, adjuvant therapy, and
      treatment decade were candidate outcome predictors. The predominant carcinomas
      were squamous cell (n = 21), transitional cell (TCC) (n = 15), and adenocarcinoma
      (n = 14). For adjuvant therapy, 20 patients had radiation (8 preoperatively), 2
      had radiation + chemotherapy, and 1 had chemotherapy alone. During mean follow-up
      of 12.8 years, 27 patients had recurrence; 15 local only, 2 distant only and 10
      local + distant. Of patients undergoing partial urethrectomy for pT1-3 tumors,
      6/27 (22%) had urethral recurrence. Overall, there were no bladder recurrences.
      Recurrence-free survival +/- standard error (SE) at 10 years was 45 + 8%. Those
      who recurred had a cancer mortality rate of 71% at 5 years postrecurrence. The
      estimated 10-year cancer-specific survival (CSS) and crude survival (CS) rates
      were 60 +/- 8% and 42 +/- 7%, respectively. Pathologic stage was predictive for
      local recurrence (P = 0.02) and CSS (P = 0.01). Positive nodes on pathology were
      related to local and distant recurrence and CSS (P = 0.01). Upon review, partial
      urethrectomy resulted in a high urethral recurrence rate (22%) with no bladder
      recurrences. These patients may be better served with radical urethrectomy and
      creation of continent catheterizable stoma.

PMID- 15464920
TI  - 9-Nitrocamptothecin as second line chemotherapy for men with progressive,
      metastatic, hormone refractory prostate cancer: Results of the CALGB 99901.
AB  - BACKGROUND: Institution of early hormone therapy in the PSA era coupled with
      demonstration of clinical benefit with chemotherapy in hormone refractory
      prostate cancer (HRPC) and acceptance of PSA decline as a surrogate for response
      has resulted in introduction of chemotherapy earlier in the natural history of
      disease. There now exists a need to identify, effective agents for second line
      chemotherapy. 9-nitrocamptothecin (9-NC) a novel, oral camptothecin analogue was
      tested as second line chemotherapy for patients with progressive hormone
      refractory prostate cancer. PATIENTS AND METHODS: Eligible patients had
      metastatic hormone refractory prostate cancer with performance status (0-1)
      following progression on at least 1 prior cytotoxic chemotherapy. 9-NC was
      administered orally at the dose of 1.5 mg/m2/d for 5 days each week for 3 weeks,
      followed by rest for 1 week. Response was evaluated after 2 cycles according to
      the guidelines set forth for Phase II trials in HRPC by the PSA working group.
      RESULTS: Thirty-five patients were recruited to the study within a period of 6
      months; 33 were evaluable for analysis. No patients had a >50% decline in PSA
      levels. Two out of 8 (25%) patients with measurable disease and 5/25 (20%)
      patients with nonmeasurable disease showed stable disease. The median time to
      disease and PSA progression was 2 months [95% confidence interval (CI), 0.9-2.8].
      The median overall survival was 10 months (95% CI = 5-12). Seven patients are
      alive after a median follow-up of 23 months. CONCLUSIONS: 9-nitrocamptothecin
      failed to elicit clinical or PSA responses. Further study in pretreated HRPC
      patients is not warranted.

PMID- 15464922
TI  - Cystic renal cell carcinoma: biology and clinical behavior.
AB  - The purpose of the study was to evaluate unilocular and multilocular cystic renal
      cell carcinoma (cRCC). These tumors are a rare entity, comprising approximately 1
      to 2% of all renal tumors, and their true biologic behavior is not well-known.
      Initial review of renal cell carcinoma (RCC) cases treated at our institution
      between 1989 and 2001 identified 39 cases of cRCC. However, histopathologic
      review of these cases by 2 pathologists revealed that only 18 cases met the
      criteria that all tumors have a cystic component that constitutes at least 75% of
      the total lesion without evidence of necrosis. These cases were compared to 614
      conventional clear cell RCC cases with regards to clinical outcomes. All 18
      patients presented with localized (N0M0) disease. Thirteen (72%) of the tumors
      were Fuhrman Grade 1, while the remaining 5 (28%) were Fuhrman Grade 2. By
      comparison, only 60% of the clear cell RCC tumors were Grade 1 or 2. Similarly,
      83% of cRCC were pT1 tumors compared to only 35% of conventional clear cell
      tumors. Mean tumor size for the cRCC tumors was 4.9 cm compared to 7.4 cm for
      conventional clear cell tumors. Cystic RCC patients had an 82% four-year disease
      specific survival (DSS). Unilocular and multilocular cRCC is a distinct subtype
      of clear cell RCC. Its biology appears to be more favorable with regards to
      important prognostic factors such as metastatic presentation, Fuhrman grade, 1997
      T stage, and tumor size. These findings suggest that cRCC patients may benefit
      from nephron sparing surgery.

PMID- 15464923
TI  - Lycopene: a novel drug therapy in hormone refractory metastatic prostate cancer.
AB  - OBJECTIVE: In a prospective study we evaluated the efficacy of lycopene for the
      treatment of patients with metastatic hormone refractory prostate cancer.
      MATERIAL AND METHODS: Between January 2001 and December 2002, 20 consecutive
      patients (median age 72; range 56-90) with metastatic HRPC were enrolled in the
      study. Lycopene in the dose of 10 mg/day was administered for a period of 3
      months. Inclusion criteria were patients previously treated with hormonal therapy
      now with clinical and biochemical evidence of disease progression. A complete
      response (CR) was defined as a normalization of PSA (<4 ng/mL) and the
      disappearance of any sign of disease for at least 8 weeks. A partial response was
      defined as a >50% decrease in PSA level for at least 8 weeks associated with
      improvement (or no worsening) in ECOG PS and relief of bone pain if present.
      Stable disease (SD) was defined as a <50% decrease or <25% increase in the PSA
      level associated with no worsening of ECOG PS and/or bone pain for at least 8
      weeks. RESULTS: One patient (5%) had complete response. Partial response was
      achieved in 6 (30%), disease remained stable in 10 (50%) and progressed in three
      (15%) patients. ECOG PS was Grade 0 in five, Grade I in 10 and Grade II in five
      of the 20 patients. It improved from Grade I to 0 in seven and Grade II to I in
      three patients. It deteriorated in three and remained unchanged in the rest seven
      patients. Bone pain was present in 16 (Grade 1 in six and Grade 2 in 10) of the
      20 patients. Grade 1 changed to Grade 0 in five and Grade II changed to Grade 1
      in five patients. Bone pain remained unchanged in 5 (31%) and worsened in 1 (6%).
      Ten (62%) patients managed to cut down the dose of analgesics on daily basis.
      Eighteen patients had associated LUTS, which improved (Q max > or = 12 mL/sec) in
      11 (61%) patients. The median duration of response was 25 weeks (range 12-72
      weeks). No drug intolerance or toxicity was encountered in any patient.
      CONCLUSIONS: Lycopene therapy appears to be effective and safe in the treatment
      of HRPC. It not only takes care of the rising PSA but also improves the ECOG
      performance status, bone pain and LUTS. Because of its relative innocuousness it
      should be tried before the use of more toxic substances.

PMID- 15464924
TI  - Familial primary mediastinal nonseminomatous germ-cell tumors.
AB  - In this article, we describe the case of 4 brothers, 2 of which had primary
      mediastinal nonseminomatous germ cell tumors (PMNSGCT), while the other 2 had
      benign mediastinal disease. We discuss the relationship between these diseases of
      the mediastinum and the thymic microenvironment. Additionally, we suggest that a
      genetic predisposition for germ-cell tumors (GCT) may be involved since the
      parents were relatives.

PMID- 15464925
TI  - Renal angiomyolipoma with liposarcomatous transformation: a case report and
      review of the literature.
AB  - Renal angiomyolipoma is generally benign, although an uncommon subtype
      (epithelioid angiomyolipoma) may behave more aggressively. Sarcomatous
      transformation of the disease is exceedingly rare. We report the first case of a
      high grade round cell liposarcoma arising in a renal angiomyolipoma.

PMID- 15464926
TI  - The importance of re-evaluation in patients with cystitis glandularis associated
      with pelvic lipomatosis: a case report.
AB  - Pelvic lipomatosis is a rare, proliferative disease involving an overgrowth of
      normal fat in the pelvic retroperitoneal space. Cystitis glandularis, cystitis
      cystica, or cystitis follicularis can be observed in 75% of patients with pelvic
      lipomatosis. We describe a 58-yr-old man with pelvic lipomatosis in whom
      adenocarcinoma of the bladder was diagnosed in the second transurethral resection
      of the bladder 1 month after the first operation. This proliferative disease can
      cause obstruction of the bladder drainage leading to a proliferative cystitis
      because of an altered environment rich in protein fluid. Because the association
      of this proliferative disease with adenocarcinoma of the bladder is frequent, we
      recommend close follow-up of these patients to detect the associated
      adenocarcinoma of the bladder.

PMID- 15464941
TI  - Elevated troponin-I after percutaneous coronary interventions: incidence and risk
      factors.
AB  - BACKGROUND: Percutaneous coronary interventions (PCIs) are often complicated by
      postprocedural myocardial necrosis as manifested by elevated cardiac markers.
      PURPOSE: To assess the incidence and risk factors of elevated troponin-I (TnI)
      after PCI. METHODS AND RESULTS: We performed a retrospective analysis on 522 PCI
      cases over a 1-year period at a single center. An elevated postprocedural TnI
      (>1.0 ng/ml) occurred in 213 patients (40.8%). Overall, glycoprotein (GP)
      IIb/IIIa inhibitors were used in 52% of cases. Baseline clinical characteristics
      were similar between the positive and the negative TnI groups. A univariate
      analysis revealed that patients with elevated TnI post-PCI had significantly more
      multivessel (28% vs. 15%, P = .001) and multilesion interventions (44% vs. 27%,
      P<.0001). The lesions were longer, more often angulated and involving
      bifurcations, and more complex in the TnI-positive group. Stent use and number of
      stents was higher in the TnI-positive group, and longer inflation times (>30 s)
      or higher inflation pressures (>14 atm) were used more often in the TnI-positive
      group. GP IIb/IIIa inhibitor use was higher in the TnI-positive group (61% vs.
      45%, P = .0007). After multivariable analysis, independent predictors of elevated
      TnI after PCI included multilesion intervention, lesion length, lesion
      angulation, and GP IIb/IIIa inhibitor use. CONCLUSION: TnI is elevated in
      approximately 40% of cases after PCI. TnI is more likely to be elevated after
      intervention on multiple lesions, angulated or long lesions.

PMID- 15464942
TI  - Addition of heparin to contrast media is associated with increased bleeding and
      peripheral vascular complications during percutaneous coronary intervention with
      bivalirudin and drug-eluting stents.
AB  - BACKGROUND: Nonionic radiographic contrast media (CM) is reported to be
      thrombogenic while performing diagnostic or interventional procedures. To avoid
      thrombosis, heparin is often added to the CM. Bivalirudin, used to replace
      heparin during percutaneous coronary intervention (PCI), is reported to be
      associated with reduced bleeding complications. We aimed to evaluate the impact
      of adding heparin to the CM during PCI in patients (pts) who underwent sirolimus
      eluting stent (SES) implantation when bivalirudin was utilized as the sole
      antithrombotic agent. METHODS: A total of 664 pts with 756 lesions underwent
      standard PCI with SES for various coronary artery lesions. Pts were treated with
      either bivalirudin only (the bivalirudin group; 0.75 mg/kg bolus and 1.75 mg/kg/h
      infusion, n = 323 pts) or bivalirudin (same dose) plus low-dose heparin added to
      the CM (the heparin mix group; mean dose = 2101.8+/-882.5 U, n = 341 pts) during
      PCI. The periprocedural, in-hospital, and 30-day clinical outcomes were compared.
      RESULTS: Baseline clinical and angiographic parameters were similar between both
      groups. Periprocedural, in-hospital, and 1-month clinical outcomes, including
      thrombotic complications, were similar between the two groups. There was no
      difference in the periprocedural thrombosis rate between the groups. In the
      heparin mix group, the overall incidence of hematoma was significantly higher
      (3.8% vs. 8.5%, P = .01), there was a trend toward higher rates of blood
      transfusion (2.6% vs. 6.6%, P = .06) and overall vascular complications (0.01%
      vs. 5.3%, P <.001), including pseudoaneurysm (PSA; 0.0% vs. 2.6%, P = .004), and
      pts who required surgical repair (0.3% vs. 1.8%, P = .07). CONCLUSIONS: The
      routine addition of low-dose heparin to CM during contemporary PCI does not add
      any protection value and is associated with higher rates of bleeding and vascular
      complications.

PMID- 15464943
TI  - Transcoronary sinus administration of autologous bone marrow in patients with
      chronic refractory stable angina Phase 1.
AB  - PURPOSE: Based on our preclinic studies with autologous unfractionated bone
      marrow (AUBM) via coronary sinus with transitory occlusion, a clinic study in
      patients with chronic stable angina was designed. The objectives were to evaluate
      safety, tolerance and feasibility. METHODS AND MATERIALS: A multicenter
      prospective study with inclusion and exclusion criteria defined by an Independent
      Clinical Committee was carried out. Fourteen patients underwent transcoronary
      sinus administration of freshly aspirated and filtered AUBM (60-120 ml). Safety
      and tolerance were evaluated. Feasibility was evaluated with Seattle Angina
      Questionnaire (SAQ), Canadian Cardiovascular Society (CCS) angina classification
      (baseline-Day 180), myocardial perfusion (baseline-Day 90) with independent core
      laboratory and coronary angiography (baseline and Day 30). RESULTS: There were no
      changes in the safety and tolerance parameters. Preliminary clinical efficacy at
      Day 180 disclosed a significant improvement of 38%, evaluated by the SAQ. The CCS
      angina classification shows that the mean angina class was 3.0+/-0.55 at baseline
      and improved to 2.0+/-0.00 at Day 180 (P <.001). Semiquantitative radionuclide
      perfusion imaging (core lab) showed a significant improvement at Day 90 in 13/14
      patients, with a mean improvement of 24% at rest (P <.01) and 33% at stress (P
      <.05). Coronary angiography showed more collateral vessels in 9/14 patients.
      CONCLUSIONS: We can conclude that AUBM via coronary sinus with transitory
      occlusion is tolerable and safe. Significant improvement in the myocardial
      perfusion at Day 90 and in the quality of life at Day 180 was observed.

PMID- 15464944
TI  - Predictors of 32P beta brachytherapy failure in patients with high-risk in-stent
      restenosis.
AB  - BACKGROUND: The effectiveness of coronary radiation therapy for the treatment of
      in-stent restenosis (ISR) has been established in several randomized clinical
      trials. The efficacy of this treatment in the general population is less well
      established. METHODS AND MATERIALS: We report our experience in 118 consecutive
      patients with nonselected high-risk ISR who had undergone successful percutaneous
      coronary intervention and brachytherapy with (32)P beta-irradiation and who were
      prospectively enrolled in a quantitative angiographic and clinical follow-up
      protocol at 7 months after the index procedure. The aim of this study was to
      investigate the independent predictor of angiographic restenosis after (32)P
      brachytherapy treatment. RESULTS: Of the patients, 28.8% were diabetics. The mean
      lesion and mean radiated lengths were, respectively, 30.1 +/- 17.2 and 43.8 +/-
      16.9 mm. The ISR pattern was diffuse in 96% of the treated lesions; in
      particular, 22.1% presented an occlusive pattern and 37.1% a proliferative
      pattern. At follow-up angiographic, restenosis and major adverse cardiac events
      (MACE) rates were, respectively, 20.8% and 29.6%. The univariate predictors of
      angiographic restenosis were procedural geographic miss, pattern IV ISR, manual
      pullback maneuver of the radiation source, preprocedural lesion percentage
      stenosis and preprocedural lesion MLD. At logistic regression analysis, only
      geographic miss and pattern IV ISR were independent predictors of post
      intracoronary radiation therapy (IRT) angiographic restenosis. CONCLUSION: These
      data indicate that 7-month angiographic restenosis after (32)P IRT in complex
      patients with ISR is not a frequent event and is predicted mainly by an occlusive
      lesion at baseline and by procedural geographical miss.

PMID- 15464945
TI  - New perspectives in the treatment of damaged myocardium using autologous skeletal
      myoblasts.
AB  - Autologous skeletal myoblast transplantation may be used to ameliorate the
      healing process following myocardium infarct and, hopefully, cardiomyopathies.
      Despite successful animal experimentation, several issues need to be addressed in
      clinical settings, i.e., the impact of the delivery route, the extent of short-
      and long-term survival, and differentiation of the injected skeletal myoblasts.
      The authors offer some new hypotheses resulting from basic research, i.e., where
      and when to inject the myogenic cells, whatever their source, how to decrease new
      myofiber atrophy and improve their regeneration. Although these new hypotheses
      still need to be tested in humans, they may be decisive for future experimental
      studies and will lead to making endovascular cell implantation a more effective
      way to treat ischemic heart disease and failure.

PMID- 15464946
TI  - Effects of off-centering on dose uniformity along and around blood vessels
      undergoing catheter-based intravascular brachytherapy.
AB  - PURPOSE: In intravascular brachytherapy, either photon or beta emitters are often
      used in a linear arrangement so that blood vessels of lengths in the range of
      several centimeters can be treated. With a line source, the dose uniformity and
      the range of doses that various components of the blood vessels receive depend
      not only on the type of radionuclides used in the treatment but also on the
      geometric position of radioactive source relative to the blood vessel walls. The
      aim of this study is to investigate the dose uniformity around the blood vessel
      and the effects on the uniformity due to the changes of the off-centering of
      different photon and beta emitters within the lumen. MATERIALS AND METHODS: Dose
      distributions were calculated on a cylindrical blood vessel of various radii. The
      radioactive sources of (192)Ir, (125)I, (103)Pd, (188)Re, (32)P, and (90)Y/Sr
      were studied. All the sources were assumed to be in the form of a line and had a
      length of 2 cm. The dose rate at a point in space produced by a radioactive
      source was computed by integrating the point dose rate kernel of the
      corresponding radionuclide over the 2-cm-long radioactive line. The point dose
      rate kernel was computed with Monte Carlo simulation of radiation transport.
      Dosimetric calculations were performed for both concentric and nonconcentric
      radioactive line source locations. Off-centering effects on the dosimetry were
      characterized with two newly defined quantities LDU and ADU: LDU describes the
      longitudinal dose uniformity along blood vessels and ADU describes the azimuthal
      dose uniformity, i.e., the dose deviation from the expected delivery dose around
      blood vessels. RESULTS: The longitudinal dose uniformity did not change
      significantly with the off-center distance. The azimuthal dose uniformity around
      the blood vessel deteriorated as the off-center distance increased. The ADU was
      worse for nonconcentric beta emitters than the photon emitters. For example, if
      the off-center distance was 1 mm and the radial distance was 1.5 mm, the range of
      dose around the blood vessel on the central transverse plane (normalized to the
      corresponding dose under the concentric condition) was from 0.55 to 3.3, 0.56 to
      3.3, 0.53 to 3.4, 0.43 to 6.0, 0.38 to 4.3, and 0.31 to 4.7 for (192)Ir, (125)I,
      (103)Pd, (90)Y/Sr, (188)Re, and (32)P sources, respectively. However, it appeared
      that there existed a lower limit of underdosing (about 40% of desired delivery
      dose) caused by the off-centering for the photon emitters. It was also found that
      both ADU and LDU became almost independent of source length when the length was
      longer than or equal to 20 mm. CONCLUSIONS: A generalized formalism for
      expressing the dose uniformity along and around blood vessels generated with a
      linear source was developed and used to study the longitudinal and azimuthal dose
      uniformity for different types of radionuclides. Although concentric beta
      emitters provide uniform dose coverage along blood vessels, nonconcentric beta
      emitters produced larger dose deviations and worse dose uniformity around the
      blood vessels than photon emitters. The off-centering introduced significantly
      higher dose on proximal vessel walls for both beta and photon emitters; however,
      the underdosing at distal points due to off-centering was somewhat limited for
      the high-energy photon emitters. The magnitude of off-centering effects for the
      low-energy photon emitters ((103)Pd) was less than that for beta emitters but
      more than that for higher energy photon emitters ((125)I and (192)Ir).

PMID- 15464947
TI  - Peroxisome proliferator-activated receptor gamma: its role in metabolic syndrome.
AB  - Here we review PPARgamma function in relation to human adipogenesis, insulin
      sensitization, lipid metabolism, blood pressure regulation and prothrombotic
      state to perhaps provide justification for this nuclear receptor remaining a key
      therapeutic target for the continuing development of agents to treat human
      metabolic syndrome.

PMID- 15464948
TI  - Development of a nanoparticle-based surface-modified fluorescence assay for the
      detection of prion proteins.
AB  - A nanoparticle-based immunoassay for the detection of recombinant bovine prion
      protein (PrP) was developed as a step in the development of screening tools for
      the prevention of the spread of transmissible spongiform encephalopathies. The
      assay is based on the competitive binding between PrP and a peptide-fluorophore
      to a nanoparticle-labeled antibody which is specific for a conserved prion
      sequence. The fluorophore, when bound to the antibody, is subject to surfaced
      modified fluorescence, enabling detection of changes in the concentration of
      bound fluorophore in the presence of prion protein. Important factors considered
      during the development of the assay were ease of use, robustness, and detection
      level. The effects of pH and nanoparticle conjugation chemistry on surface
      modified fluorescence observed in the assay were explored. Effects of
      concentrations of antibody and fluorophore on reproducibility and detection
      limits were examined. At present, the detection limits of the system are
      approximately equal to the antibody-peptide fluorophore equilibrium dissociation
      constant, which is near one nanomolar concentration. Improved assay performance
      could be obtained by optimization of the nanoparticle surface resonance effects.
      The simplicity of the assay and ease of use may make the type of assay described
      in this report attractive for screening purposes in the food industry.

PMID- 15464949
TI  - Comparative analysis of inducible expression systems in transient transfection
      studies.
AB  - Ectopic protein expression in mammalian cells is a valuable tool to analyze
      protein functions. Increasingly, inducible promoters are being used for regulated
      gene expression. Here, we compare expression maxima, induction rates, and
      "leakiness" of the following promoter systems: (I) two tetracycline-responsive
      Tet systems (Tet-On, Tet-Off), (II) the glucocorticoid-responsive mouse mammary
      tumor virus promoter (MMTVprom), (III) the ecdysone-inducible promoter (EcP), and
      (IV) the T7 promoter/T7 RNA polymerase system (T7P). The systems were analyzed by
      expressing an enhanced green fluorescent protein (EGFP) luciferase fusion
      reporter protein in transiently transfected cells. Expression was assessed
      qualitatively by fluorescence microscopy of the EGFP component and quantitatively
      by measuring the enzymatic activity of the luciferase component of the fusion
      protein. Basal expression levels ("leakiness") were ranked Tet-On>Tet
      Off>MMTVprom>EcP>T7P. Induction rates were EcP>MMTVprom>T7P>Tet-Off>Tet-On.
      Expression maxima were ranked. Tet-On>Tet-Off>MMTVprom>EcP>T7P. To increase T7
      promoter-mediated expression we inserted an internal ribosomal entry site element
      into the T7 expression cassette. In presence of T7 RNA polymerase this modified
      T7 promoter achieved expression levels of 42% of a Rous Sarcoma virus promoter,
      while keeping basal expression extremely low.

PMID- 15464950
TI  - Profiling the morphological distribution of O-linked oligosaccharides.
AB  - The morphological distribution of oligosaccharides is determined in the egg jelly
      surrounding Xenopus laevis eggs. This biological system is used to illustrate a
      method for readily identifying and quantifying oligosaccharides in specific
      tissues. The extracellular matrix surrounding X. laevis eggs consists of a
      vitelline envelope and a jelly coat. The jelly coat contains three
      morphologically distinct layers designated J1, J2, and J3 from the innermost to
      the outermost and is composed of 9-11 distinct glycoproteins. Each jelly layer is
      known to have specific functions in the fertilization of the egg. We developed a
      rapid method to separate and identify the oligosaccharides from X. laevis egg
      jelly layers. Identification was based on the retention times in high-performance
      liquid chromatography (porous graphitized carbon column), exact masses, and
      tandem mass spectrometry. Over 40 neutral and 30 sulfated oligosaccharides were
      observed in the three jelly layers. Neutral oligosaccharide structures from
      different jelly layers were both unique and overlapping, while sulfated
      oligosaccharides were detected only in layers J1 and J2. Neutral oligosaccharides
      unique to jelly layer J3 and the combined layers J1+J2 had similar core
      structures and similar residues. However, differences between these two sets of
      unique oligosaccharides were also observed and were primarily due to the
      branching carbohydrate moieties rather than the core structures.

PMID- 15464951
TI  - Fluorescence polarization as an analytical tool to evaluate galectin-ligand
      interactions.
AB  - Galectins are a family of beta-galactose binding lectins associated with
      functions such as immunological and malignant events. To study the binding
      affinity of galectins for natural and artificial saccharides and glycoconjugates
      we have developed an assay using fluorescence polarization. A collection of
      fluorescein-conjugated saccharides was synthesized and used as probes with
      galectins-1 and -3 and the two carbohydrate recognition domains of galectin-4.
      Direct binding of a fixed probe amount with different amounts of each galectin
      defined specificity and selectivity and permitted selection of the optimal probe
      for inhibition studies. Then fixed amounts of galectin and selected probe were
      used to screen the inhibitory potency of a library of nonfluorescent compounds.
      As the assay is in solution and does not require separation of free and bound
      probe, it is simple and rapid and can easily be applied to different unlabeled
      galectins. As all interaction components are known, K(d) values for galectin
      inhibitor interaction can be directly calculated without approximation other than
      the assumption of a simple one-site competition.

PMID- 15464952
TI  - Identification of alternative products and optimization of 2-nitro-5
      thiocyanatobenzoic acid cyanylation and cleavage at cysteine residues.
AB  - The reagent 2-nitro-5-thiocyanatobenzoic acid (NTCB) is commonly used to
      cyanylate and cleave proteins at cysteine residues, but this two-step reaction
      requires lengthy incubations and produces highly incomplete cleavages. In
      previous reports, incomplete cleavage was attributed to a competing beta
      elimination reaction that converts cyanylated cysteine to dehydroalanine. In this
      study, previously unidentified side reactions of the NTCB cleavage were
      discovered and beta-elimination was not the major reaction competing with peptide
      bond cleavage. A major side reaction was identified as carbamylation of lysine
      residues. Carbamylation could be minimized by desalting the cyanylation reaction
      before cleavage or by reducing the reactant concentrations, but both methods
      suffered from further reductions in cleavage efficiency. Based on model peptide
      studies, poor cleavage was primarily caused by a mass neutral rearrangement of
      the cyanylated cysteine which produced a cleavage-resistant, nonreducible
      product. The formation of this product could be minimized by using stronger
      nucleophiles for the cleavage reaction. We discovered that base-catalyzed
      nucleophilic cleavage could be achieved with many amino-containing compounds.
      Most notably, glycine is capable of promoting efficient cleavage. In addition,
      efficient NTCB cleavage can be performed in a simple one-step method without a
      prior cyanylation step, rather than the previously described two-step reaction.

PMID- 15464953
TI  - Potentiometric characterization of ethidium bromide and of its reactions with
      nucleic acids.
AB  - A liquid membrane electrode that allows the concentration of ethidium ion (Ed(+))
      to be measured selectively and accurately in the range of 0.1 microM to 5 mM is
      made. For Ed(+) concentrations less than 1 microM or more than 0.1 mM, the trend
      is no longer linear, and the causes of this behavior are discussed. The mean
      activity coefficient of ethidium bromide exhibits deviations from the Debye
      Huckel limiting law that are interpreted in terms of aggregate formation. The
      stability constants for Ed(2)(2+) and Ed(2)Br(+) are 230 kg mol(-1) and 3.0 x
      10(4) kg(2) mol(-2), respectively. In NaCl solutions, clusters involving up to 4
      Ed(+) units are detected and their stability constants are evaluated. The
      intercalation of ethidium into poly(A).poly(U) in 1M NaCl is investigated by the
      above electrode, and the results are compared with those obtained by
      spectrophotometry. The data are analyzed in terms of Scatchard plots. The
      potentiometric method is more accurate than the spectrophotometric one at low
      values of the binding degree (r) where negative deviations from linearity are
      observed. The deviations are ascribed to a cooperative behavior rather than to
      artifacts caused by minor systematic errors.

PMID- 15464954
TI  - Fluorescence resonance energy transfer-based detection of analytes using
      antiidiotypic affinity protein pairs.
AB  - A new method for specific detection of proteins based on fluorescence resonance
      energy transfer (FRET) using affinity proteins (affibodies) derived from
      combinatorial engineering of Staphylococcal protein A has been developed.
      Antiidiotypic affibody pairs were used in a homogeneous competitive binding
      assay, where the idiotypic, target-specific affibody was labeled with fluorescein
      and the antiidiotypic affibody was labeled with tetramethylrhodamine.
      Intermolecular FRET between the two fluorescent probes was observed in the
      antiidiotypic affibody complex, but upon addition of target protein the
      antiidiotypic affibody was displaced, which was monitored by a shift in the
      relative emission of the donor and acceptor fluorophores. The feasibility of the
      system was demonstrated by the detection of IgA and Taq DNA polymerase with high
      specificity, using two different antiidiotypic affibody pairs. Detection of Taq
      DNA polymerase in 25% human plasma was successfully carried out, demonstrating
      that the method can be used for analysis of proteins in samples of complex
      composition.

PMID- 15464955
TI  - Chip-based gel electrophoresis method for the quantification of half-antibody
      species in IgG4 and their by- and degradation products.
AB  - The inter-heavy-chain disulfide bonds of the IgG4 subclass can be described as
      being at equilibrium with the intra-chain disulfide bonds. This means that a
      fraction of IgG4 has noncovalently linked heavy chains (half-antibody). The
      percentage of half-antibodies produced depends upon the expression system used.
      Nondenaturing assays fail to separate the half-antibodies from the native form
      because two half-molecules are held together by noncovalent forces. The
      pharmaceutical industry needs a reliable denaturing assay for checking batch-to
      batch consistency. Until now sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) has been the standard method used to detect the
      presence of half-antibodies. However, this technique is laborious and cannot be
      automated. Furthermore, cumbersome densitometric measurements are necessary for
      quantification. To overcome these disadvantages a chip-based gel electrophoresis
      method was investigated. In the nonreduced format the separation profile is
      compared with that from SDS-PAGE. The limit of quantification as a percentage of
      the amount applied, repeatability, reproducibility, and linearity are compared
      with those of SDS-PAGE. The amounts of half-antibody and of by- and degradation
      products were determined for several batches by using area percentage and by
      external calibration with IgG4 as a reference standard. Both methods allow
      avoidance of error introduction for the quantification as is the case by
      application of myosin as reference concentration. Both sets of results are
      compared with each other and with the results from SDS-PAGE. In the reduced
      format it is noted that the reduction of the inter-heavy-chain disulfide bridges
      proceeds faster than the reduction of the heavy-light-chain bonds. Therefore
      optimized conditions are necessary to obtain a complete reduction.

PMID- 15464956
TI  - Simultaneous fluorometric measurement of histamine and tele-methylhistamine
      levels in rodent brain by high-performance liquid chromatography.
AB  - An improved high-performance liquid chromatography (HPLC) method was developed
      for simultaneous analysis of histamine (HA) and tele-methylhistamine (tele-MHA)
      levels in mouse and rat brain. The method consists of a solid-phase extraction
      (SPE) and subsequent HPLC with postcolumn derivatization of the amines with o
      phthalaldehyde. The recovery rates of HA and tele-MHA during the SPE procedure
      were 82.8+/-3.4 and 86.0+/-1.7%, respectively. The detection limits for HA and
      tele-MHA were 8 and 12pg, respectively, with sufficient linearity up to 30pg.
      Using this newly developed system, we observed that the brain tele-MHA levels in
      H3 receptor knockout mice were significantly higher than those of wild-type mice
      by 2.1-fold. Furthermore, we also observed that the brain HA and tele-MHA levels
      in Zucker rats were significantly lower than those of lean rats by 76.6+/-5.3 and
      77.8+/-5.0%, respectively. These observations coincided well with those of
      previous studies using radioimmunoassay or HPLC with precolumn OPA
      derivatization, confirming the utilization of the assay system.

PMID- 15464957
TI  - Changes in structure and stability of calbindin-D(28K) upon calcium binding.
AB  - Calbindin-D(28K) is a biologically important protein required for normal neural
      function and for the transport of calcium in epithelial cells of the intestine
      and kidney. We have used fluorescence and circular dichroism (CD) spectroscopy to
      characterize the effects of calcium binding on the structure and stability of
      calbindin. Ca(2+) titration monitored by fluorescence spectroscopy reveals the
      presence of two classes of calcium-binding sites with association constants
      approximately 10(7.5) and approximately 10(8.9)M(-1). CD spectra in the far-UV
      spectral range show minor changes upon Ca(2+) titration, implying that the
      secondary structure of calbindin-D(28K) is not greatly affected. On the basis of
      the CD spectra in the near-UV spectral range, we conclude that the tertiary
      structure is more sensitive to Ca(2+) addition. The most significant change
      occurs between pCa 7.0 and pCa 8.0. The variations in the protein thermostability
      are correlated with those in the near-UV CD spectra. The enthalpy changes upon
      heat denaturation of calbindin in the apo-state are characteristic of proteins
      containing several weakly interacting domains with similar thermodynamical
      properties. Thus, calcium binding by calbindin-D(28K) largely affects the local
      structure around the aromatic residues and the thermal stability of the protein;
      the changes in the secondary structure are insignificant.

PMID- 15464958
TI  - Catching and separating protein ligands by functional affinity electrophoresis.
AB  - A new kind of affinity electrophoresis called functional affinity electrophoresis
      (FAEP) is a technique used to separate and/or capture proteins according to their
      functions in a native polyacrylamide gel. Protein A:immunoglobulin G,
      avidin:biotin, antibody:antigen, and concanavalin A:glycoprotein interactions are
      used to demonstrate this technique. Protein A, avidin, monoclonal anti-bovine
      serum albumin (BSA) antibody, and concanavalin A are embedded in distinct regions
      of a 7.5% native polyacrylamide gel. Some of each of the embedded proteins get
      covalently and/or noncovalently incorporated into the gel matrix network. Under
      electrophoresis conditions, these proteins do not show significant
      electrophoretic mobility or they migrate in a direction opposite to the protein
      analytes, as in avidin. We clearly observe that polyclonal anti-human myoglobin
      antibody, biotinylated insulin, BSA, and ovalbumin (glycoprotein) are captured
      and separated in distinct regions of a FAEP gel by protein A, avidin, monoclonal
      anti-BSA antibody, and concanavalin A, respectively.

PMID- 15464959
TI  - On-chip micro-flow polystyrene bead-based immunoassay for quantitative detection
      of tacrolimus (FK506).
AB  - Tacrolimus (FK506) is a widely used immunosuppressant for preventing allograft
      rejection and the treatment of atopic dermatitis. FK506 necessitates therapeutic
      drug monitoring because of inter- and intrapatient variability and the lack of
      correlation between the administered dose and the blood concentration. Previous
      immunoassay-based methods required a relatively long assay time and troublesome
      liquid-handling procedures. In the present study, we aimed to establish a rapid
      monitoring method for FK506 determination by using a poly(dimethylsiloxane)
      (PDMS)-based microfluidic device. Polystyrene beads were coated with mouse anti
      FK506 antibody and placed in the flow channel. As a competitive assay, sample
      solution was allowed to react in the flow channel. After the addition of the
      fluorogenic substrate, the fluorescent signal was observed under a microscope. As
      a result, the developed assay allowed a short detection time of approximately 15
      min per each sample and a high sensitivity even by using only a single bead. The
      feasibility of performing a competitive assay using a PDMS-based antibody chip
      gives promising results over the existing immunoassay-based methods.

PMID- 15464960
TI  - Noninvasive methods to determine the critical micelle concentration of some bile
      acid salts.
AB  - In this work the critical micelle concentrations (cmc) of four bile salts, sodium
      cholate, sodium glycocholate, sodium deoxycholate, and sodium glycodeoxycholate,
      are determined and presented. Three independent noninvasive methodologies
      (potentiometry, derivative spectrophotometry, and light scattering) were used for
      cmc determination, at 25 degrees C with ionic strength adjusted to 0.10 M with
      NaCl. Spectrophotometric and potentiometric studies of some bile salts were also
      executed at various ionic strength values, thus allowing the influence of the
      ionic strength on the cmc value of the bile salt to be assessed. A critical
      comparison of the cmc values obtained with data collected from the literature is
      presented. Furthermore, this work makes an evaluation of the conceptual bases of
      different methodologies commonly used for cmc determination, since variations in
      the results obtained can be related mainly to different intrinsic features of the
      methods used (such as sensitivity or the need to include tracers or probes) or to
      the operational cmc definition applied. The undoubted definition of the
      experimental bile salt concentration that corresponds to cmc (operational cmc) is
      essential since in the case of these amphiphiles the formation of micelles is not
      as abrupt as in the case of ordinary association colloids. The biphasic nature of
      their aggregation leads to a "round-shaped" variation of the experimental
      parameters under analysis, which makes difficult the evaluation of the cmc values
      and can be responsible for the different results obtained.

PMID- 15464961
TI  - Bienzymatic amperometric biosensor for choline based on mediator thionine in situ
      electropolymerized within a carbon paste electrode.
AB  - An amperometric enzyme biosensor for the determination of choline utilizing two
      enzymes, choline oxidase (CHOD) and horseradish peroxidase (HRP), is described.
      The biosensor consisted of CHOD cross-linked onto a HRP-immobilized carbon paste
      electrode. The biosensor was prepared by in situ electropolymerization of
      poly(thionine) within a carbon paste containing the enzyme HRP and thionine
      monomer and then CHOD was immobilized by using chitosan film through cross
      linking with glutaraldehyde. The in situ electrogenerated poly(thionine) displays
      excellent electron transform efficiency between the enzyme HRP and the electrode
      surface, and the polymer enables improvement in enzyme immobilization within the
      paste. Several parameters such as the amount of thionine and enzyme, the applied
      potential, the pH, etc. have been studied. Amperometric detection of choline was
      realized at an applied potential of -0.2V vs saturated calomel electrode in 1/15M
      phosphate buffer solution (pH 7.4) with a linear response range between 5.0 x 10(
      6) and 6.0 x 10(-4)M choline and a response time of 15s. When applied to the
      analysis of phosphatidylcholine in serum samples, a 0.997 correlation was
      obtained between the biosensor results and those obtained by a hospital method.

PMID- 15464962
TI  - Ultrasensitive detection of biomolecules with fluorescent dye-doped
      nanoparticles.
AB  - Fluorescent-labeled molecules have been used extensively for a wide range of
      applications in biological detection and diagnosis. A new form of highly
      luminescent and photostable nanoparticles was generated by doping the fluorescent
      dye tris(2'2-bipyridyl)dichlororuthenium(II)hexahydrate (Rubpy) inside silica
      material. Because thousands of fluorescent dye molecules are encapsulated in the
      silica matrix that also serves to protect Rubpy dye from photodamaging oxidation,
      the Rubpy-dye-doped nanoparticles are extremely bright and photostable. We have
      used these nanoparticles successfully in various fluorescence labeling
      techniques, including fluorescent-linked immunosorbent assay,
      immunocytochemistry, immunohistochemistry, DNA microarray, and protein
      microarray. By combining the high-intensity luminescent nanoparticles with the
      specificity of antibody-mediated recognition, ultrasensitive target detection has
      been achieved. In all cases, assay results clearly demonstrated the superiority
      of the nanoparticles over organic fluorescent dye molecules and quantum dots in
      probe labeling for sensitive target detection. These results demonstrate the
      potential to apply these newly developed fluorescent nanoparticles in various
      biodetection systems.

PMID- 15464963
TI  - Kinetic analysis-based quantitation of free radical generation in EPR spin
      trapping.
AB  - Because short-lived reactive oxygen radicals such as superoxide have been
      implicated in a variety of disease processes, methods to measure their production
      quantitatively in biological systems are critical for understanding disease
      pathophysiology. Electron paramagnetic resonance (EPR) spin trapping is a direct
      and sensitive technique that has been used to study radical formation in
      biological systems. Short-lived oxygen free radicals react with the spin trap and
      produce paramagnetic adducts with much higher stability than that of the free
      radicals. In many cases, the quantity of the measured adduct is considered to be
      an adequate measure of the amount of the free radical generated. Although the
      intensity of the EPR signal reflects the magnitude of free radical generation,
      the actual quantity of radicals produced may be different due to modulation of
      the spin adduct kinetics caused by a variety of factors. Because the kinetics of
      spin trapping in biochemical and cellular systems is a complex process that is
      altered by the biochemical and cellular environment, it is not always possible to
      define all of the reactions that occur and the related kinetic parameters of the
      spin-trapping process. We present a method based on a combination of measured
      kinetic data for the formation and decay of the spin adduct alone with the
      parameters that control the kinetics of spin trapping and radical generation. The
      method is applied to quantitate superoxide trapping with 5-diethoxyphosphoryl-5
      methyl-1-pyrroline N-oxide (DEPMPO). In principle, this method is broadly
      applicable to enable spin trapping-based quantitative determination of free
      radical generation in complex biological systems.

PMID- 15464964
TI  - Determination of pyrrolized phospholipids in oxidized phospholipid vesicles and
      lipoproteins.
AB  - The Ehrlich reaction was optimized to determine pyrrolized phospholipids produced
      as a consequence of oxidative stress. The procedure consisted of the treatment of
      the modified phospholipids with p-(dimethylamino)benzaldehyde at a controlled
      acidity temperature and the spectrophotometric determination of adducts produced.
      The extinction coefficient of Ehrlich adducts was calculated by using 1-[1-(2
      hydroxyethyl)-1H-pyrrol-2-yl]propan-1-ol (compound 1) as standard and was 56,500
      M(-1)cm(-1). The response was linear and reproducible within the range of 0.051
      7.65 microM of compound 1. When the assay was applied to determination of pyrrole
      content in ethanolamine incubated in the presence of 0.25-1mM of 4,5(E)-epoxy
      2(E)-heptenal, the complete conversion of the aldehyde into the pyrrole ring was
      observed and the results obtained were similar to those found when compound 1 was
      determined by gas chromatography. When phosphatidylethanolamine was incubated in
      the presence of 0.5-40 mM of 4,5(E)-epoxy-2(E)-heptenal, the phospholipid was
      pyrrolized similarly to ethanolamine, although there was not a quantitative
      conversion and the amount of pyrroles produced depended on the pH of the media.
      Pyrrolized phospholipids were also produced when phosphatidylethanolamine
      multilamellar vesicles where oxidized in the presence of either Fe(3+)/ascorbic
      acid or ABAP (2,2'-azobis(2-methylpropionamide) dihydrochloride) and when high
      density lipoproteins were incubated in the presence of Cu(2+), thereby confirming
      that phospholipid pyrrolization is a common consequence of oxidative stress and
      that Ehrlich adducts may be valid for determining this pyrrolization.

PMID- 15464965
TI  - Optimized RNA amplification using T7-RNA-polymerase based in vitro transcription.
AB  - The use of expression profiling to explore a cell's transcriptional landscape has
      exploded in recent years. In many cases, however, the very limited amount of
      starting material poses a major problem, making the amplification of the isolated
      RNA obligatory. The most prominent amplification method used was developed by the
      Eberwine lab in 1990: cDNA synthesis is started with an oligo(dT) primer
      containing a T7 RNA polymerase promoter. After second-strand synthesis RNA is
      transcribed in vitro using T7 RNA polymerase. It has been demonstrated that
      antisense RNA amplification not only preserves the fidelity of RNA-based
      microarray analysis but even improves the sensitivity. In our aim to improve the
      yield of in vitro transcription reactions and to facilitate the use of amplified
      RNA for the construction of cDNA libraries we tested a series of T7 primers with
      different 3' flanking sequences containing restriction sites. In addition we
      tested the impact of different DNA polymerases used for synthesizing the
      templates on the efficiency of the in vitro transcription reaction. A total of 28
      different oligo(dT)-T7 promoter primers were tested. Two of them showed a
      dramatically increased yield of RNA from the in vitro transcription reaction. The
      combination of the improved second-strand synthesis with the new T7 primer
      increased the RNA yield 60-fold compared to the yield of standard procedures.

PMID- 15464966
TI  - The determination of the asymmetrical stereochemical distribution of fatty acids
      in triacylglycerols.
AB  - The fatty acid distribution in triacylglycerols (TAGs) is a factor that
      contributes to the intrinsic properties of oils from different species variants.
      Many hypotheses have been proposed to explain the specific distribution of fatty
      acids in the different naturally occurring oils. Currently, the 1,3-random-2
      random theory is more or less accepted, but it has been widely shown that most
      vegetable oils do not behave randomly in the sn-1 and sn-3 stereochemical
      positions. For this reason, complex methodologies have been developed to analyze
      the fatty acid composition of the three stereochemical positions in TAGs. In this
      article, we propose that by calculating the asymmetric alpha coefficient, the
      stereochemical asymmetry of fatty acids in TAG molecular species can be defined.
      This coefficient reflects the relative content of fatty acids at the sn-1 and sn
      3 positions and may overcome the problems found mainly with complex sn-1, sn-2,
      and sn-3 stereochemical analysis of fatty acids in TAG. The alpha coefficient is
      calculated from the fatty acid, sn-2 fatty acid, and TAG composition of the oil.
      Indeed, through this coefficient, it has been possible to show that, despite
      having the same overall content, the stearic acid distribution in the sn-1 and sn
      3 positions is not random in some oils.

PMID- 15464967
TI  - Simultaneous determination of renal clinical analytes in serum using hydrolase-
      and oxidase-encapsulated optical array biosensors.
AB  - An optical array biosensor encapsulated with hydrolase and oxidoreductase using
      sol-gel immobilization technique has been fabricated for simultaneous analysis
      and screening of multiple samples to determine the presence of multianalytes
      which are clinically important in relation to renal failure. Urease and
      creatinine deiminase were used to detect urea and creatinine, while glucose
      oxidase and uricase were coimmobilized with horseradish peroxidase to quantify
      glucose and uric acid. Moreover, the concentrations of analytes in fetal calf
      serum were measured and quantified using the developed sensing system. The array
      biosensor showed good specificity for the simultaneous analysis of multiple
      samples for multianalytes without obvious cross-interference. The analytical
      ranges of the four analytes were between 0.01 and 10mM with detection limits of
      2.5-80 microM. High precision with relative standard deviations of 3.8-9.2%
      (n=45) was also demonstrated. The reproducibility of array-to-array in 3
      consecutive months was 5.4% (n=3). Moreover, the concentrations of analytes in
      fetal calf serum were 5.9 mM for urea, 0.13 mM for creatinine, 3.3mM for glucose,
      and 0.15 mM for uric acid, which were in good agreement with results obtained
      using the traditional spectroscopic methods. These results demonstrate the first
      use of a sol-gel-derived optical array biosensor for simultaneous analysis of
      multiple samples for the presence of multiple clinically important renal
      analytes.

PMID- 15464968
TI  - Nonenzymatic preparative-scale synthesis of dityrosine and 3-bromotyrosine.

PMID- 15464969
TI  - A spectrophotometric assay for the quantification of polyethylenimine in DNA
      nanoparticles.

PMID- 15464970
TI  - An economic and efficient method of RNAi vector constructions.

PMID- 15464971
TI  - Genotyping of the triallelic variant G2677T/A in MDR1 using LightCycler with
      locked-nucleic-acid-modified hybridization probes.

PMID- 15464972
TI  - Nonlinear fitting of bisubstrate enzyme kinetic models using SAS computer
      software: application to R67 dihydrofolate reductase.

PMID- 15464973
TI  - How reliable re-adjustment is: correspondence regarding A. Fuglsang, "The
      'effective number of codons' revisited".
AB  - A. Fuglsang [Biochem. Biophys. Res. Commun. 317 (2004) 957-964] suggested that
      effective number of codons for individual amino acids (Nc-values) should be re
      adjusted to the number of synonymous codons of those amino acids, in order to
      prevent the overestimation of the effective number of codons. Here, it is shown
      that re-adjustment at the level of individual amino acids results in loss of
      considerable amounts of information. Furthermore, we have shown that theoretical
      Nc-values are functions of GC3s (and GC1s); as a result, when an amino acid Nc
      value exceeds the related theoretical Nc-value, the implication of re-adjustment
      depends on the GC composition of the gene.

PMID- 15464974
TI  - Effects of IL-1beta on gene expression in human rheumatoid synovial fibroblasts.
AB  - IL-1 is one of the key mediators involved in the pathogenesis of rheumatoid
      arthritis (RA) and is known to affect the level of gene expression in various
      settings. We investigated the effects of IL-1beta on the expression of 240 genes
      in rheumatoid synovial fibroblasts (RSFs) using a cDNA microarray. Total RNAs
      were prepared from RSFs stimulated with IL-1beta and hybridized to the
      microarray. The fluorescence intensity of each gene was compared between the
      control and IL-1beta-treated cells. To confirm the data obtained from the
      microarray analysis, the level of gene expression was also examined by ELISA,
      Northern blot, or Western blot depending on the genes to be analyzed. The genes
      whose levels were significantly changed by IL-1beta in the microarray analysis
      could be divided into three categories; inflammatory mediators, matrix-modifying
      enzymes, and apoptosis-associated molecules. The increase in the mRNA levels of
      IL-6, IL-8, MCP-1, and GRO-1 was confirmed by determining their protein levels
      from the cell culture supernatant using ELISA. The increase in the level of two
      matrix-degrading enzymes, MMP-1 and MMP-3, was reproducibly observed by an ELISA
      method, while the decrease in the level of TIMP-3, an inhibitor of MMPs, was
      confirmed by Northern blot analysis. The fluorescence intensity of two apoptosis
      related genes, caspase-3 and Bcl-xL, was significantly lowered. The decreased
      protein level of caspase-3 was also found. Our data suggested that IL-1beta could
      provoke a series of responses in RSFs leading to the pathologic status of RA,
      including enhancement of inflammatory cytokines, imbalanced production of MMPs
      and TIMPs, and dysregulation of apoptosis.

PMID- 15464975
TI  - HDACi phenylbutyrate increases bystander killing of HSV-tk transfected glioma
      cells.
AB  - Malignant glioma patients have a dismal prognosis with an urgent need of new
      treatment modalities. Previously developed gene therapies for brain tumors showed
      promising results in experimental animal models, but failed in clinical trials
      due to low transfection rates and insufficient expression of the transgene in
      tumor cells, as well as low bystander killing effects. We have previously shown
      that the histone deacetylase inhibitor 4-phenylbutyrate (4-PB) enhances gap
      junction communication between glioma cells in culture. In this study, we
      demonstrate an activation of recombinant HSV-tk gene expression, and a dramatic
      enhancement of gap junction-mediated bystander killing effect by administration
      of the HSV-tk prodrug ganciclovir together with 4-PB. These findings that 4-PB
      potentiates "suicide gene" expression as well as enhances gap junctional
      communication and bystander killing of tumor cells justify further testing of
      this paradigm as an adjunct to suicide gene therapy of malignant gliomas.

PMID- 15464977
TI  - Site-directed mutagenesis to enable and improve crystallizability of Candida
      tropicalis (3R)-hydroxyacyl-CoA dehydrogenase.
AB  - The N-terminal part of Candida tropicalis MFE-2 (MFE-2(h2Delta)) having two (3R)
      hydroxyacyl-CoA dehydrogenases with different substrate specificities has been
      purified and crystallized as a recombinant protein. The expressed construct was
      modified so that a stabile, homogeneous protein could be obtained instead of an
      unstabile wild-type form with a large amount of cleavage products. Cubic crystals
      with unit cell parameters a=74.895, b=78.340, c=95.445, and alpha=beta=gamma=90
      degrees were obtained by using PEG 4000 as a precipitant. The crystals exhibit
      the space group P2(1)2(1)2(1) and contain one molecule, consisting of two
      different (3R)-hydroxyacyl-CoA dehydrogenases, in the asymmetric unit. The
      crystals diffract to a resolution of 2.2A at a conventional X-ray source.

PMID- 15464976
TI  - Serial analysis of gene expression in sinusoidal endothelial cells from normal
      and injured mouse liver.
AB  - Here we describe gene expression profiles of mouse liver sinusoidal endothelial
      cells (LSECs) revealed by serial analysis of gene expression (SAGE). We prepared
      SAGE libraries of LSECs from normal and injured liver by CCl(4) administration,
      and we obtained 32,867 tags from normal and 37,493 tags from injured liver,
      representing 6011 unique transcripts. CCl(4) administration upregulated several
      genes related to cell growth and differentiation (Cdkn1a, Irf1, Il4ra, etc.),
      whereas it downregulated genes related to cell growth or protein transport (Kdr,
      Igfbp4, Ap1b1, etc.). To identify genes preferentially expressed in LSEC, we
      compared our SAGE libraries with 77 publicly available libraries generated from
      various mouse tissues and cell lines. We identified 23 genes, including Stab2 and
      uncharacterized genes, as possible markers for LSEC, which will be useful to
      analyze the specific role for LSECs in normal as well as regenerating liver.

PMID- 15464978
TI  - Interferon-gamma regulates ClC-2 chloride channel in lung epithelial cells.
AB  - Epithelial Cl(-) channels mediate Cl(-) and fluid secretion in the lung. In
      cystic fibrosis, aberrant Cl(-) secretion is one of the major causes for lung
      fluid imbalance. Regulation of Cl(-) channels is therefore an important issue in
      the lung. IFN-gamma regulates Na(+) and Cl(-) channels and fluid transport in the
      lung, but the mechanisms involved in these regulations are not clear. In
      expression studies, we found that IFN-gamma increased ClC-2 transcripts in Calu-3
      cells. Studies of the promoter identified a minimal promoter which interacts with
      transcription factors Sp1 and Sp3. However, reporter gene assays showed that IFN
      gamma did not activate the promoter. Instead, IFN-gamma significantly increased
      ClC-2 transcript stability. Using Ussing chamber experiments, we demonstrate that
      IFN-gamma activates a pH-regulated and Cd(2+)-sensitive short circuit current,
      characteristic properties of the ClC-2 Cl(-) channel. These data suggest that IFN
      gamma activates ClC-2 channel activity in lung epithelial cells via mRNA
      stabilization.

PMID- 15464979
TI  - Aluminum as a specific inhibitor of plant TPC1 Ca2+ channels.
AB  - In plant cells, Al ion plays dual roles as an inducer and an inhibitor of Ca(2+)
      influx depending on the concentration. Here, the effects of Al on Ca(2+)
      signaling were assessed in tobacco BY-2 cells expressing aequorin and a putative
      plant Ca(2+) channel from Arabidopsis thaliana, AtTPC1 (two-pore channel 1). In
      wild-type cells (expressing only aequorin), Al treatment induced the generation
      of superoxide, and Ca(2+) influx was secondarily induced by superoxide. Higher Al
      concentrations inhibited the Al-stimulated and superoxide-mediated Ca(2+) influx,
      indicating that Ca(2+) channels responsive to reactive oxygen species (ROS) are
      blocked by high concentration of Al. H(2)O(2)-induced Ca(2+) influx was also
      inhibited by Al. Thus, inhibitory action of Al against ROS-induced Ca(2+) influx
      was confirmed. Similarly, known Ca(2+) channel blockers such as ions of La and Gd
      inhibited the H(2)O(2)-induced Ca(2+) influx. While La also inhibited the
      hypoosmotically induced Ca(2+) influx, Al showed no inhibitory effect against the
      hypoosmotic Ca(2+) influx. The effects of Al and La on Ca(2+) influx were also
      tested in the cell line overexpressing AtTPC1 and the cell line AtTPC1
      dependently cosuppressing the endogenous TPC1 equivalents. Notably,
      responsiveness to H(2)O(2) was lost in the cosuppression cell line, thus TPC1
      channels are required for ROS-responsive Ca(2+) influx. Data also suggested that
      hypoosmotic shock induces TPC1-independent Ca(2+) influx and Al shows no
      inhibitory action against the TPC1-independent event. In addition, AtTPC1
      overexpression resulted in a marked increase in Al-sensitive Ca(2+) influx,
      indicating that TPC1 channels participate in osmotic Ca(2+) influx only when
      overexpressed. We concluded that members of TPC1 channel family are the only ROS
      responsive Ca(2+) channels and are the possible targets of Al-dependent
      inhibition.

PMID- 15464980
TI  - Molecular cloning and characterization of rat and human calpain-5.
AB  - Until today, 14 isoforms of mammalian calpains have been identified, including
      calpain-5. The C. elegans calpain-5 homologue tra-3 is reported to be essential
      for necrotic neuronal cell death. In this study, we cloned and characterized rat
      calpain-5, which is highly homologous to human and mouse sequences. The
      nucleotide sequence is 87% and 93% identical with human and mouse calpain-5,
      respectively. The protein sequence is well conserved, showing 96% identity in
      mouse and 92% in human. RT-PCR analysis revealed strong expression of calpain-5
      in rat lungs, kidneys, and brain while week expression in heart, whereas in rat
      brain regions it is ubiquitously expressed. The mRNA expression in different
      human tissues showed equal expression. However, in human brain regions calpain-5
      was strongly expressed in hypothalamus, thalamus, cerebellum, and frontal lobe.
      Western blot analysis on human neuroblastoma SH-SY5Y cells demonstrated calcium
      dependent processing of calpain-5, despite the absence of calmodulin-like domain.

PMID- 15464981
TI  - Cyclin D1 and p22ack1 play opposite roles in plant growth and development.
AB  - The plant cell division cycle, a highly coordinated process, is continually
      regulated during the growth and development of plants. In this report, we
      demonstrate how two cell-cycle regulators act together to control cell
      proliferation in transgenic Arabidopsis. To identify potential cyclin dependent
      kinase regulators from Arabidopsis, we employed an two-hybrid screening system to
      isolate genes encoding G1 specific cyclin-interacting proteins. One of these,
      p22(ack1), which encodes a novel 22kDa protein, binds to cyclin D1.
      Overexpression of p22(ack1) in transgenic Arabidopsis resulted in growth
      retardation due to a strong inhibition of cell division in the leaf primordial
      and meristematic tissue. The leaf shape of p22(ack1) transgenic Arabidopsis was
      altered from oval in wild-type to dentate. Wild-type phenotype was successfully
      restored in F1 hybrids by cross-hybridizing the p22(ackl)Arabidopsis mutants with
      cyclin D1. Taken together, these results suggest that p22(ack1) and cyclin D1,
      which act antagonistically, are major rate-limiting factors for cell division in
      the leaf meristem.

PMID- 15464982
TI  - Differential DNA methylation reprogramming of various repetitive sequences in
      mouse preimplantation embryos.
AB  - Genome-wide changes of DNA methylation by active and passive demethylation
      processes are typical features during preimplantation development. Here we
      provide an insight that epigenetic reprogramming of DNA methylation is regulated
      in a region-specific manner, not a genome-wide fashion. To address this
      hypothesis, methylation states of three repetitive genomic regions were monitored
      at various developmental stages in the mouse embryos. Active demethylation was
      not observed in the IAP sequences whereas methylation reprogramming of the
      satellite sequences was regulated only by the active mechanism. Etn elements were
      actively demethylated after fertilization, passively demethylated by the 8-cell
      stage, and de novo methylated at the morular and blastocyst stages, showing
      dynamic epigenetic changes. Thus, our findings suggest that the specific genomic
      regions or sequences may spatially/temporally have their unique characteristics
      in the reprogramming of the DNA methylation during preimplantation development.

PMID- 15464983
TI  - Beta-amyloid-derived pentapeptide RIIGLa inhibits Abeta(1-42) aggregation and
      toxicity.
AB  - Pr-IIGL(a), a derivative of the tetrapeptide beta-amyloid 31-34 (Abeta(31-34)),
      exerts controversial effects: it is toxic in a neuroblastoma culture, but it
      protects glial cells from the cytotoxic action of Abeta(1-42). For an
      understanding of this phenomenon, a new pentapeptide, RIIGL(a) was synthetized,
      and both compounds were studied by different physicochemical and biological
      methods. Transmission electron microscopic (TEM) studies revealed that Pr-IIGL(a)
      forms fibrillar aggregates, whereas RIIGL(a) does not form fibrils. Congo red
      binding studies furnished the same results. Aggregated Pr-IIGL(a) acts as a
      cytotoxic agent in neuroblastoma cultures, but RIIGL(a) does not display inherent
      toxicity. RIIGL(a) co-incubated with Abeta(1-42) inhibits the formation of mature
      amyloid fibres (TEM studies) and reduces the cytotoxic effect of fibrillar
      Abeta(1-42). These results indicate that RIIGL(a) is an effective inhibitor of
      both the aggregation and the toxic effects of Abeta(1-42) and can serve as a lead
      compound for the design of novel neuroprotective peptidomimetics.

PMID- 15464984
TI  - Functional interaction between Smad, CREB binding protein, and p68 RNA helicase.
AB  - The transforming growth factors beta control a diversity of biological processes
      including cellular proliferation, differentiation, apoptosis, and extracellular
      matrix production, and are critical effectors of embryonic patterning and
      development, including that of the orofacial region. TGFbeta superfamily members
      signal through specific cell surface receptors that phosphorylate the cytoplasmic
      Smad proteins, resulting in their translocation to the nucleus and interaction
      with promoters of TGFbeta-responsive genes. Subsequent alterations in
      transcription are cell type-specific and dependent on recruitment to the
      Smad/transcription factor complex of coactivators, such as CBP and p300, or
      corepressors, such as c-ski and SnoN. Since the affinity of Smads for DNA is
      generally low, additional accessory proteins that facilitate Smad/DNA binding are
      required, and are often cell- and tissue-specific. In order to identify novel
      Smad 3 binding proteins in developing orofacial tissue, a yeast two hybrid assay
      was employed in which the MH2 domain of Smad 3 was used to screen an expression
      library derived from mouse embryonic orofacial tissue. The RNA helicase, p68, was
      identified as a unique Smad binding protein, and the specificity of the
      interaction was confirmed through various in vitro and in vivo assays. Co
      expression of Smad 3 and a CBP-Gal4 DNA binding domain fusion protein in a Gal4
      luciferase reporter assay resulted in increased TGFbeta-stimulated reporter gene
      transcription. Moreover, co-expression of p68 RNA helicase along with Smad 3 and
      CBP-Gal4 resulted in synergistic activation of Gal4-luciferase reporter
      expression. Collectively, these data indicate that the RNA helicase, p68, can
      directly interact with Smad 3 resulting in formation of a transcriptionally
      active ternary complex containing Smad 3, p68, and CBP. This offers a means of
      enhancing TGFbeta-mediated cellular responses in developing orofacial tissue.

PMID- 15464985
TI  - Heme-dependent up-regulation of the alpha-globin gene expression by
      transcriptional repressor Bach1 in erythroid cells.
AB  - The transcriptional factor Bach1 forms a heterodimer with small Maf family, and
      functions as a repressor of the Maf recognition element (MARE) in vivo. To
      investigate the involvement of Bach1 in the heme-dependent regulation of the
      expression of the alpha-globin gene, human erythroleukemia K562 cells were
      cultured with succinylacetone (SA), a heme biosynthetic inhibitor, and the level
      of alpha-globin mRNA was examined. A decrease of alpha-globin mRNA was observed
      in SA-treated cells, which was restored by the addition of hemin. The heme
      dependent expression of alpha-globin occurred at the transcriptional level since
      the expression of human alpha-globin gene promoter-reporter gene containing
      hypersensitive site-40 (HS-40) was decreased when K562 cells were cultured with
      SA. Hemin treatment restored the decrease of the promoter activity by SA. The
      regulation of the HS-40 activity by heme was dependent on the NF-E2/AP-1 (NA)
      site, which is similar to MARE. The NA site-binding activity of Bach1 in K562
      increased upon SA-treatment, and the increase was diminished by the addition of
      hemin. The transient expression of Bach1 and mutated Bach1 lacking CP motifs
      suppressed the HS-40 activity, and cancellation of the repressor activity by
      hemin was observed when wild-type Bach1 was expressed. The expression of NF-E2
      strengthened the restoration of the Bach1-effect by hemin. Interestingly, nuclear
      localization of Bach1 increased when cells were treated with SA, while hemin
      induced the nuclear export of Bach1. These results indicated that heme plays an
      important role in the induction of alpha-globin gene expression through
      disrupting the interaction of Bach1 and the NA site in HS-40 enhancer in
      erythroid cells.

PMID- 15464986
TI  - Production of Vibrio vulnificus hemolysin in vivo and its pathogenic
      significance.
AB  - Hemolyin/cytolysin (VvhA) is one of the representative exotoxins produced by
      Vibrio vulnificus. Cytotoxic mechanism of VvhA has been extensively studied.
      However, there have been controversies concerning the pathogenic significance
      since vvhA(-) mutant showed no LD(50) change in mice. In this study, we
      investigated whether VvhA is expressed in vivo. When V. vulnificus was cultured
      in the presence of normal pooled human serum, substantial amount of VvhA was
      detected by ELISA and the transcription of vvhA was also evidently confirmed by
      RT-PCR and a transcriptional reporter assay. To investigate whether VvhA is
      expressed in vivo, mice were infected with V. vulnificus and bacterial RNAs were
      harvested from the mice. In vivo vvhA transcription was observed evidently by RT
      PCR. We hereby propose that VvhA is substantially produced in vivo and would
      contribute to the pathogenesis of V. vulnificus septicemia.

PMID- 15464987
TI  - Reduced serum dipeptidyl peptidase-IV after metformin and pioglitazone
      treatments.
AB  - Dipeptidyl peptidase-IV (DPP-IV) regulates metabolism by degrading incretins
      involved in nutritional regulation. Metformin and pioglitazone improve insulin
      sensitivity whereas glyburide promotes insulin secretion. Zucker diabetic rats
      were treated with these antidiabetic agents for 2 weeks and DPP-IV activity and
      expression were determined. Serum DPP-IV activity increased whereas tissue
      activity decreased as the rats aged. Treatment of rats with metformin,
      pioglitazone, and glyburide did not alter DPP-IV mRNA expression in liver or
      kidney. Metformin and pioglitazone significantly (P<0.05) reduced serum DPP-IV
      activity and glycosylated hemoglobin. Glyburide did not lower DPP-IV activity or
      glycosylated hemoglobin. Regression analysis showed serum DPP-IV activity
      correlated with glycosylated hemoglobin (r=0.92) and glucagon-like peptide-1
      levels (r=-0.49). Metformin, pioglitazone, and glyburide had no effect on serum
      DPP-IV activity in vitro, indicating these are not competitive DPP-IV inhibitors.
      We propose the in vivo inhibitory effects observed with metformin and
      pioglitazone on serum DPP-IV activity results from reduced DPP-IV secretion.

PMID- 15464988
TI  - Highly sensitive cell-based assay system to monitor the sialyl Lewis X
      biosynthesis mediated by alpha1-3 fucosyltransferase-VII.
AB  - The sialyl Lewis X (sLe(x)) determinant on leukocytes serves as a ligand for
      selectin family cell adhesion molecules, and selectin-carbohydrate interaction is
      considered to play an important role in the process of leukocyte extravasation
      during inflammation. Among several alpha1-3 fucosyltransferases (FucTs), FucT-VII
      plays a critical role in the biosynthesis of sLe(x)-epitopes. Therefore, small
      molecules specifically designed to inhibit the FucT-VII enzyme may have potential
      as anti-inflammatory agents. Here, we have developed a versatile cell-based assay
      system to monitor sLe(x) biosynthesis using the GeneSwitch System. This system is
      a mifepristone (MFP)-inducible mammalian expression system, and human
      transfectant T lymphoblasts expressed the mRNA of FucT-VII and the sLe(x)
      epitopes on the cell surface in a time-dependent manner in the presence of MFP,
      with very low background transcription. Furthermore, when the transfectants were
      treated with the FucT-VII inhibitor panosialin, sLe(x) expression on the induced
      cells was inhibited dose dependently without alteration at the mRNA level of FucT
      VII. These results suggest that the FucT-VII may be a major regulator of the
      biosynthesis of the sLe(x)-epitopes on T lymphoblasts, and this cell-based assay
      may be utilized for a screening system of FucT-VII inhibitors.

PMID- 15464989
TI  - Hinnuliquinone, a C2-symmetric dimeric non-peptide fungal metabolite inhibitor of
      HIV-1 protease.
AB  - HIV-1 protease is one of several key enzymes required for the replication and
      maturation of HIV-1 virus. An almost two-decade research effort by academic and
      pharmaceutical institutions resulted in the successful commercialization of seven
      drugs that are potent inhibitors of HIV-1 protease activity and which, if used
      correctly, are highly effective in managing viral load. However, identification
      of clinical viral isolates that are resistant to these drugs indicates that this
      is a significant problem and that new classes of inhibitors are continually
      needed. Screening of microbial extracts followed by bioassay-guided isolation led
      to the discovery of a natural hinnuliquinone, a C(2)-symmetric bis-indolyl
      quinone natural product that inhibited the wild-type and a clinically resistant
      (A44) strain of HIV-1 protease with K(i) values of 0.97 and 1.25microM,
      respectively. Crystallographic analysis of the inhibitor-bound HIV-1 protease
      helped explain the importance of the C(2)-symmetry of hinnuliquinone for
      activity. Details of the isolation, biological activity, and crystallographic
      analysis of the inhibitor-bound protease are herein described.

PMID- 15464990
TI  - The effect of long-term treatment with erythromycin on Th1 and Th2 cytokines in
      diffuse panbronchiolitis.
AB  - Diffuse panbronchiolitis (DPB) is a chronic progressive disease of the
      respiratory bronchioles, and has been improved by low-dose, long-term
      erythromycin (EMC) treatment. The therapeutic benefits may be derived from its
      anti-inflammatory and immunomodulatory properties rather than antimicrobial
      effect. However, there are few studies about the mechanism of immunomodulation by
      EMC treatment for patient with DPB. In this study, we quantified the changes of
      Th1 and Th2 cytokines in the bronchoalveolar lavage (BAL) fluid from patients
      with DPB after long term treatment with EMC. After the EMC treatment, a
      significant reduction in the number of lymphocytes was observed, and the CD4/CD8
      ratio was elevated as well. The IL-2 and IFN-gamma levels in the BAL fluid were
      significantly decreased and the IL-4, IL-5, and IL-13 levels were significantly
      increased after EMC treatment. Our results suggest that the therapeutic benefits
      of long-term EMC treatment may be partially due to the immune system's shift from
      Th1 to Th2 cytokine production.

PMID- 15464991
TI  - Upregulation of guanylyl cyclase expression and activity in striatum of MPTP
      induced parkinsonism in mice.
AB  - The aim of our study was to investigate the expression and the activity of
      soluble guanylyl cyclase (GC) and phosphodiesterase (PDE) activities that
      regulate cGMP level in the striatum, hippocampus, and brain cortex in an animal
      model of PD, induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We
      observed the increase of total activity and protein level of GC in striatum after
      MPTP injection. It was accompanied by an enhancement of both mRNA expression and
      protein level of GCbeta1 subunit. MPTP induces mRNA expression and elevates
      protein concentration of GCbeta1 in striatum up to 14 days after its injection,
      which in turn causes a marked enhancement of cGMP formation. Furthermore, the
      activation of GC occurs through change of maximal enzyme activity (V(max)).
      Simultaneously, no change in PDE activity has been detected in all investigated
      regions of the brain after MPTP. MPTP injection caused the elevation of GCbeta1
      protein level in both the membrane and cytosol fractions being significantly
      higher in cytosol. Western blot analysis demonstrated about 45-67% decrease of
      tyrosine hydroxylase protein content in striatum. These data suggest that NO/cGMP
      signaling pathway may at least partially contribute to dopaminergic fiber
      degeneration in the striatum, the damage attributed to PD.

PMID- 15464992
TI  - Arsenic binding to Fucus vesiculosus metallothionein.
AB  - The seaweed Fucus vesiculosus is a member of the brown algae family. Kille and co
      workers [Biochem. J. 338 (1999) 553] reported that this species contains the gene
      for metallothionein. Metallothionein is a metalloprotein having low molecular
      weight, and high cysteine content, which binds a range of metals. F. vesiculosus
      bioaccumulates arsenic from the aquatic environment [Mar. Chem. 18 (1986) 321].
      In this paper we describe arsenic binding to F. vesiculosus metallothionein,
      characterized by electrospray ionization mass spectrometry. Five arsenic-MT
      species were detected with increasing As to protein ratios. These results provide
      important information about the metal-chelation behaviour of this novel algal
      metallothionein which is a putative model for arsenic binding to F. vesiculosus
      in vivo.

PMID- 15464993
TI  - Rodent lymphocytes express functionally active glutamate receptors.
AB  - RT-PCR demonstrated that ionotropic (iGluR NR1) and metabotropic (mGluR Group
      III) glutamate receptors are expressed in rodent lymphocytes. Flow cytometry
      showed that activation of iGluR NR1 by N-methyl-D-aspartate (NMDA) increased
      intracellular free calcium and reactive oxygen species (ROS) levels and activated
      caspase-3. The latter effect was attenuated by the NMDA antagonist, 5-methyl
      10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), by the antioxidant
      N-acetylcysteine and by cyclosporin A. Treatment with L-2-amino-4
      phosphonobutyric acid (L-AP4), an mGluR Group III agonist, increased lymphocyte
      ROS levels but to a lower extent than did NMDA. Activation of lymphocytes with
      both NMDA and L-AP4 caused a synergistic increase in ROS levels and induced
      necrotic cellular death without elevating the caspase-3 activation observed in
      the presence of NMDA alone. These results show that lymphocyte iGluR NR1 and
      mGluR Group III receptors may be involved in controlling rodent lymphocyte
      functions and longevity as they regulate events in cell proliferation,
      maturation, and death.

PMID- 15464994
TI  - Coordination of oxidized protein hydrolase and the proteasome in the clearance of
      cytotoxic denatured proteins.
AB  - Intracellular accumulation of denatured proteins impairs cellular function. The
      proteasome is recognized as an enzyme responsible for the effective clearance of
      those cytotoxic denatured proteins. As another enzyme that participates in the
      destruction of damaged proteins, we have identified oxidized protein hydrolase
      (OPH) and found that OPH confers cellular resistance to various kinds of
      oxidative stress. In this study, we demonstrate the roles of the proteasome and
      OPH in the clearance of denatured proteins. The inhibition of proteasome activity
      results in the elevation of protein carbonyls in cells under oxidative stress. On
      the other hand, cells overexpressing OPH retain higher resistance to oxidative
      stress, even though the proteasome activity is inhibited. Furthermore, upon
      inhibition of the proteasome activity, OPH is recruited to a novel organelle
      termed the aggresome where misfolded or denatured proteins are processed. Thus,
      OPH and the proteasome coordinately contribute to the clearance of cytotoxic
      denatured proteins.

PMID- 15464995
TI  - Effects of flanking genes on the phenotypes of mice deficient in basigin/CD147.
AB  - The induction of null mutations by means of homologous recombination is a
      powerful technique for clarifying the biological activities of target genes.
      However, the problems of the genetic background and flanking genes should be
      borne in mind. Here we employed a breeding strategy to compare three lines of
      mice deficient in the basigin (Bsg)/CD147 gene. The first line was F2 from F1
      hybrid offspring of the 129/SV chimera and C57BL/6J. The second one was from a
      C57BL/6J congenic line. Both lines showed high embryonic lethality, sterility,
      and blindness. The third one was 'reverse F2' from 'reverse F1' hybrid offspring
      of the C57BL/6J congenic line and 129/SV. Surprisingly, this line showed a normal
      birth rate, while sterility and blindness persisted. Our results clearly separate
      the effects of the induced null mutation from those of flanking genes and the
      genetic background, and provide a useful means of investigating the biological
      functions of Bsg.

PMID- 15464996
TI  - Gangliosides of organ-confined versus metastatic androgen-receptor-negative
      prostate cancer.
AB  - Prior development of a unique androgen-receptor (AR)-negative cell line (HH870)
      from organ-confined (T2b) human prostate cancer (CaP) enabled comparison of the
      gangliosides associated with normal and neoplastic prostate epithelial cells,
      organ-confined versus metastatic (DU 145, PC-3), and AR-negative versus AR
      positive CaP cell lines. Resorcinol-HCl and specific monoclonal antibodies were
      used to characterize gangliosides on 2D-chromatograms, and to visualize them on
      the cell surface with confocal-fluorescence microscopy. AR-negative cells
      expressed GM1b, GM2, GD2, GD1a, and GM3. GM1a, GD1b, and GT1b were undetectable.
      GM1b and GD1a were more prominent in AR-negative than in AR-positive cells. PC-3
      and HH870 cells were unique in the expression of O-acetylGD2 (O-AcGD2) and two
      alpha2,3-sialidase-resistant, alkali-susceptible GMR17-reactive gangliosides.
      Expression of GD1a, GM1b, doublets of GD3, GD2, and O-AcGD2, and the presence of
      an additional alkali-labile-14.G2a-reactive ganglioside, two alkali-susceptible,
      and three alkali-resistant GMR17-reactive gangliosides makes HH870 a potential
      component of a polyvalent-vaccine for active-specific immunotherapy of CaP.

PMID- 15464997
TI  - High ER stress in beta-cells stimulates intracellular degradation of misfolded
      insulin.
AB  - Endoplasmic reticulum (ER) stress, which is caused by the accumulation of
      misfolded proteins in the ER, elicits an adaptive response, the unfolded protein
      response (UPR). One component of the UPR, the endoplasmic reticulum-associated
      protein degradation (ERAD) system, has an important function in the survival of
      ER stressed cells. Here, we show that HRD1, a component of the ERAD system, is
      upregulated in pancreatic islets of the Akita diabetes mouse model and enhances
      intracellular degradation of misfolded insulin. High ER stress in beta-cells
      stimulated mutant insulin degradation through HRD1 to protect beta-cells from ER
      stress and ensuing death. If HRD1 serves the same function in humans, it may
      serve as a target for therapeutic intervention in diabetes.

PMID- 15464998
TI  - Functional expression of human and mouse P2Y12 receptors in Saccharomyces
      cerevisiae.
AB  - DNA sequences encoding the murine ortholog of the human P2Y12 receptor were
      cloned. The human and mouse P2Y12 receptors were expressed in a yeast cell-based
      GPCR expression technology containing chimeric yeast Galpha protein (Gpa1)
      constructs in which the 5 C-terminal amino acids were identical to corresponding
      sequences from mammalian Galphai/o proteins. LacZ reporter gene assays of agonist
      induced activation of the G protein-coupled mating signal transduction pathway
      revealed murine P2Y12 functional pharmacological properties that closely
      resembled those exhibited by the human P2Y12 receptor. In NIH3T3 cells, the mouse
      P2Y12 stimulated calcium uptake monitored in FLIPR via coupling to a Galphaq/i3
      chimeric protein. Murine P2Y12 mRNA was expressed at high levels in the brain and
      at lower levels in a variety of peripheral tissues. In situ hybridization
      analysis indicated glia-specific expression within the brain.

PMID- 15464999
TI  - Inhibitory effect of organotin compounds on rat neuronal nitric oxide synthase
      through interaction with calmodulin.
AB  - Organotin compounds, triphenyltin (TPT), tributyltin, dibutyltin, and
      monobutyltin (MBT), showed potent inhibitory effects on both L-arginine oxidation
      to nitric oxide and L-citrulline, and cytochrome c reduction catalyzed by
      recombinant rat neuronal nitric oxide synthase (nNOS). The two inhibitory effects
      were almost parallel. MBT and TPT showed the highest inhibitory effects, followed
      by tributyltin and dibutyltin; TPT and MBT showed inhibition constant (IC(50))
      values of around 10microM. Cytochrome c reduction activity was markedly decreased
      by removal of calmodulin (CaM) from the complete mixture, and the decrease was
      similar to the extent of inhibition by TPT and MBT. The inhibitory effect of MBT
      on the cytochrome c reducing activity was rapidly attenuated upon dilution of the
      inhibitor, and addition of a high concentration of CaM reactivated the cytochrome
      c reduction activity inhibited by MBT. However, other cofactors such as FAD, FMN
      or tetrahydrobiopterin had no such ability. The inhibitory effect of organotin
      compounds (100microM) on L-arginine oxidation of nNOS almost vanished when the
      amount of CaM was sufficiently increased (150-300microM). It was confirmed by CaM
      agarose column chromatography that the dissociation of nNOS-CaM complex was
      induced by organotin compounds. These results indicate that organotin compounds
      disturb the interaction between CaM and nNOS, thereby inhibiting electron
      transfer from the reductase domain to cytochrome c and the oxygenase domain.

PMID- 15465000
TI  - Cytoplasmic nonsense-mediated mRNA decay for a nonsense (W262X) transcript of the
      gene responsible for hereditary tyrosinemia, fumarylacetoacetate hydrolase.
AB  - Messenger RNAs containing premature stop codons are generally targeted for
      degradation through the nonsense-mediated mRNA decay (NMD) pathway. The
      subcellular localization of the NMD process in higher eukaryotes remains
      controversial. While many mRNAs are subjected to NMD prior to their release from
      the nucleus, a few display cytoplasmic NMD. To understand the possible impact of
      NMD on the pathogenesis of hereditary tyrosinemia type I, a severe metabolic
      disease caused by fumarylacetoacetate hydrolase (FAH) deficiency, we examined the
      metabolism of FAH mRNA harboring a nonsense mutation, W262X, in lymphoblastoid
      cell lines derived from patients and their parents. W262X-FAH transcripts show a
      approximately 20-fold reduction in abundance in mutant cells, which is
      translation-dependent. Cellular fractionation shows that this down-regulation of
      the W262X transcript occurs in the cytoplasm. Thus, the W262X FAH is another
      example of nonsense mRNAs subjected to the NMD pathway in the cytoplasm.

PMID- 15465001
TI  - Medroxyprogesterone acetate attenuates estrogen-induced nitric oxide production
      in human umbilical vein endothelial cells.
AB  - We report the novel observation that medroxyprogesterone acetate (MPA) attenuates
      the induction by 17beta estradiol (E2) of both nitric oxide (NO) production and
      endothelial nitric oxide synthase (eNOS) activity in human umbilical vein
      endothelial cells. Although MPA had no effect on basal NO production or basal
      eNOS phosphorylation or activity, it attenuated the E2-induced NO production and
      eNOS phosphorylation and activity. Moreover, we examined the mechanism by which
      MPA attenuated the E2-induced NO production and eNOS phosphorylation. MPA
      attenuated the E2-induced phosphorylation of Akt, a kinase that phosphorylates
      eNOS. Treatment with pure progesterone receptor (PR) antagonist RU486 completely
      abolished the inhibitory effect of MPA on E2-induced Akt phosphorylation and eNOS
      phosphorylation. In addition, the effects of actinomycin D were tested to rule
      out the influence of genomic events mediated by nuclear PRs. Actinomycin D did
      not affect the inhibitory effect of MPA on E2-induced Akt phosphorylation.
      Furthermore, the potential roles of PRA and PRB were evaluated. In COS cells
      transfected with either PRA or PRB, MPA attenuated E2-induced Akt
      phosphorylation. These results indicate that MPA attenuated E2-induced NO
      production via an Akt cascade through PRA or PRB in a non-genomic manner.

PMID- 15465002
TI  - Identification of a novel MAGE D2 antisense RNA transcript in human tissues.
AB  - Using cDNA microarray analysis, we identified a cDNA clone, DD74, from primary
      human bronchial epithelial cells, which exhibits increased expression in vitro
      after treatment with all-trans retinoic acid. This clone corresponded to MAGE D2
      mRNA, a gene previously identified to be upregulated in several cancer tissues.
      Surprisingly, in situ hybridization of lung tissue demonstrated positive
      hybridization signals with sense, but not antisense, MAGE D2-specific cRNA
      probes. Examination of several cell lines by Northern blot hybridization
      confirmed significant expression of two RNA bands. With strand-specific
      riboprobes, we identified a 2.0kb RNA transcript with the antisense probe as
      expected and identified a 4.1kb transcript by the sense probe. Further sequence
      analysis of the 4.1kb transcript revealed at least a 509 nucleotide sequence
      exactly complementary to the 2.0kb MAGE D2 mRNA sequence. This MAGE D2i sequence
      contains unique structural features not shared with those of previously described
      antisense transcripts. Identification of this transcript potentially has
      important implications for future studies examining MAGE D2 expression patterns
      in cancer and normal tissues.

PMID- 15465003
TI  - Catabolism of heparan sulfate proteoglycans in Drosophila cell lines.
AB  - We have studied intracellular catabolism of heparan sulfate proteoglycans (HSPGs)
      in Drosophila cell lines, Kc and S2, by a series of pulse-chase experiments using
      [(35)S]sulfate as a precursor in metabolic labeling experiments. HSPGs in culture
      medium and cell layer were separately purified by serial chromatographic
      procedures using Q-Sepharose and Superose 6 for characterization. Analysis of
      intact HSPG on Superose 6 chromatography revealed that Kc and S2 cells synthesize
      one major molecular species with slightly differing in sizes (estimated to be
      54kDa in Kc and 78kDa in S2 cells). Analysis of glycosaminoglycans for (35)S
      labeled macromolecules showed that the majority of (35)S-labeled macromolecules
      in Kc and S2 cells are HSPGs ( approximately 60% and approximately 80%,
      respectively). Results from continuous labeling and 2h pulse labeling-chase
      experiments revealed that, in both cell lines, the intact HSPGs were degraded in
      multiple phases; the degradation of HSPG was rapid in the early phase (with half
      lives of approximately 6h in Kc and approximately 3h in S2 cells) and slow in the
      later phase (with half-lives >80h in both Kc and S2 cells). The rapid degradation
      appeared similar to that observed for glycosylphosphatidylinositol-anchored HSPGs
      (glypicans) in mammalian cell cultures. While the slow degradation appeared
      similar to that observed for transmembrane HSPGs (syndecans) in mammalian cell
      cultures. These experiments suggested that vertebrates and invertebrates shared
      common mechanisms for intracellular HSPG catabolism.

PMID- 15465004
TI  - Amantadine partition and localization in phospholipid membrane: a solution NMR
      study.
AB  - Quantification of membrane partition potential of drug compounds is of great
      pharmaceutical interest. Here, a novel approach combining liquid-state NMR
      diffusion measurements and fast-tumbling lipid/detergent bicelles is used to
      measure accurately the partition coefficient K(p) of amantadine in phospholipid
      bilayers. Amantadine is found to have a strong membrane partition potential, with
      K(p) of 27.6 in DMPC and 37.8 in POPC lipids. Electrostatic interaction also
      plays a major role in the drug's affinity towards biological membrane as
      introduction of negatively charged POPG dramatically increases its K(p).
      Saturation transfer difference experiments in small bicelles indicate that
      amantadine localizes near the negatively charged phosphate group and the
      hydrocarbon chain of bilayer lipid. The approach undertaken in this study is
      generally applicable for characterizing interactions between small molecules and
      phospholipid membranes.

PMID- 15465005
TI  - Butyrate response factor 1 is regulated by parathyroid hormone and bone
      morphogenetic protein-2 in osteoblastic cells.
AB  - Parathyroid hormone (PTH) exerts potent and diverse effects in bone and cartilage
      through activation of type 1 PTH receptors (PTH1R) capable of coupling to protein
      kinase A (PKA) and PKC. We have used macroarrays to identify zinc finger protein
      butyrate response factor-1 (BRF1) as a novel PTH regulated gene in clonal and
      normal osteoblasts of human and rodent origin. We further demonstrate that in
      human osteoblast-like OHS cells, biologically active hPTH(1-84) and hPTH(1-34)
      stimulate BRF1 mRNA expression in a dose- and time-dependent manner, while the
      amino-terminally truncated hPTH(3-84) which does not activate PTH1R has no
      effect. Moreover, using specific stimulators or inhibitors of PKA and PKC
      activity, the PTH-elicited BRF1 mRNA expression is mediated through the PKA
      signaling pathway. In mouse calvarial osteoblasts, BRF1 mRNA levels are
      upregulated by PTH(1-84) and reduced in response to bone morphogenetic protein 2
      (BMP-2). Hence, our data showing that BRF1 is expressed in osteoblastic cells and
      regulated by PTH and BMP-2, suggest an important role for BRF1 in osteoblasts
      within the molecular network of PTH-dependent bone remodeling.

PMID- 15465006
TI  - A novel P-I class metalloproteinase with broad substrate-cleaving activity,
      agkislysin, from Agkistrodon acutus venom.
AB  - The venom of Viperdae is a rich source of metalloproteinases, which have
      potential clinical applications for lowering plasma fibrinogen or dissolving
      thrombi. Recently, we purified a novel proteinase from Formosan Agkistrodon
      acutus venom using DEAE-Sephadex A-50 and Mono-Q HR 5/5 column chromatography.
      The purified getatinolytic component, agkislysin, is a 22kDa-monomeric protein
      without Asn-linked sugar. Functional characterization showed that agkislysin
      possessed both fibronectin- and type IV collagen-cleaving activities. In
      addition, agkislysin preferentially cleaved the Aalpha chain of fibrinogen,
      followed by the Bbeta chain, while the gamma chain was finally affected.
      Furthermore, agkislysin was also capable of cleaving prothrombin into various
      fragments, as well as suppressing ristocetin-induced platelet aggregation by
      hydrolyzing von Willebrand factor. However, the proteolytic activity of
      agkislysin was slightly enhanced by divalent metal ions and completely inhibited
      by chelating agents, but not serine proteinase inhibitor. These findings suggest
      that agkislysin is a P-I class metalloproteinase with unique biological
      properties.

PMID- 15465007
TI  - Glutathione precursors replenish decreased glutathione pool in cystinotic cell
      lines.
AB  - Cystinosis is an inherited disorder due to mutations in the CTNS gene which
      encodes cystinosin, a lysosomal transmembrane protein involved in cystine export
      to the cytosol. Both accumulation of cystine in the lysosome and decreased
      cystine in the cytosol may participate in the pathogenic mechanism underlying the
      disease. We observed that cystinotic cell lines have moderate decrease of
      glutathione content during exponential growth phase. This resulted in increased
      solicitation of oxidative defences of the cell denoted by concurrent superoxide
      dismutase induction, although without major oxidative insult under our
      experimental conditions. Finally, decreased glutathione content in cystinotic
      cell lines could be counterbalanced by a series of exogenous precursors of
      cysteine, denoting that lysosomal cystine export is a natural source of cellular
      cysteine in the studied cell lines.

PMID- 15465008
TI  - Inhibition of HIV-1 infection in cells expressing an artificial complementary
      peptide.
AB  - TLMA2993 peptide (N'-TLMALELKGKLLLAGLAPSAFLPLSFPEGL-C') which was designed by a
      computer program (MIMETIC) inhibited the activity of HIV-1 reverse transcriptase
      in a cell-free system. Therefore, we constructed a TLMA2993 expression vector
      containing an artificial cDNA for TLMA2993 to generate the peptide in cells. The
      cell lysate of transfected U937 cells contained a detectable level of TLMA2993
      peptide using competitive ELISA. The transfectants were resistant to HIV-1
      infection due to expression of TLMA2993 peptide in the cells. The use of MIMETIC
      to design an inhibitory peptide to any intracellular target molecule, followed by
      transfection of the artificial cDNA for the peptide, could afford a new approach
      for treatment and/or prevention of viral infection.

PMID- 15465009
TI  - Apoptosis in stress-induced and spontaneously senescent human fibroblasts.
AB  - Although apoptosis has been shown in vivo to be involved in the aging process, in
      vitro studies of age-dependent apoptosis are limited. In this study, apoptosis
      was examined in normal human fibroblasts exposed to H(2)O(2) to induce premature
      senescence and in spontaneously senescent human fibroblasts. Although apoptosis
      was not observed for several days after exposure to H(2)O(2), morphological
      changes indicating apoptosis were evident in about 5% of cells 7 days after
      exposure to 80microM H(2)O(2), concomitantly with expression of senescent
      phenotype. The apoptotic changes were preceded by caspase activation in majority
      of the exposed cells. As well as H(2)O(2)-induced senescent cells, spontaneously
      senescent human fibroblasts showed apoptotic changes in about 2% of cells and
      majority of the senescent cells also showed activation of caspases. The results
      indicate that the apoptosis pathway is activated in H(2)O(2)-induced and
      spontaneously senescent human fibroblasts in vitro.

PMID- 15465010
TI  - Nephrin expression is increased in anti-Thy1.1-induced glomerulonephritis in
      rats.
AB  - Nephrin is an important constituent of the glomerular filtration barrier and
      alteration of its expression is associated with severe proteinuria. In this study
      we show that injection of an anti-Thy1.1 antibody in rats not only induces a
      mesangioproliferative glomerulonephritis associated with increased proteinuria,
      but also leads to a sustained increase of nephrin mRNA and protein expression in
      renal glomeruli over a time period of 29 days. In contrast, podocin and CD2AP,
      two proteins shown to interact with nephrin in the slit diaphragm, are acutely
      downregulated at days 3-7 and, thereafter, recovered again to normal levels after
      29 days. Interestingly, immunofluorescence staining of kidney sections at day 10
      of the disease shows a highly heterogeneous pattern, in that some podocytes show
      complete absence of nephrin, whereas others show highly accumulated staining for
      nephrin compared to control sections, which in total results in an increased
      level of nephrin per glomerulus. In summary, our data show that in the course of
      mesangioproliferative glomerulonephritis in rats, an upregulation of nephrin
      expression occurs with a concomitant transient downregulation of podocin and
      CD2AP which may account for a highly dysregulated filtration barrier and
      increased proteinuria.

PMID- 15465011
TI  - N-Formylated humanin activates both formyl peptide receptor-like 1 and 2.
AB  - We have discovered that humanin (HN) acts as a ligand for formyl peptide receptor
      like 1 (FPRL1) and 2 (FPRL2). This discovery was based on our finding that HN
      suppressed forskolin-induced cAMP production in Chinese hamster ovary (CHO) cells
      expressing human FPRL1 (CHO-hFPRL1) or human FPRL2 (CHO-hFPRL2). In addition, we
      found that N-formylated HN (fHN) performed more potently as a ligand for FPRL1
      than HN: in CHO-hFPRL1 cells, the effective concentration for the half-maximal
      response (EC(50)) value of HN was 3.5nM, while that of fHN was 0.012nM. We
      demonstrated by binding experiments using [(125)I]-W peptide that HN and fHN
      directly interacted with hFPRL1 on the membrane. In addition, we found that HN
      and fHN showed strong chemotactic activity for CHO-hFPRL1 and CHO-hFPRL2 cells.
      HN is known to have a protective effect against neuronal cell death. Our findings
      contribute to the understanding of the mechanism behind HN's function.

PMID- 15465012
TI  - Human ABCA3, a product of a responsible gene for abca3 for fatal surfactant
      deficiency in newborns, exhibits unique ATP hydrolysis activity and generates
      intracellular multilamellar vesicles.
AB  - ABCA3 is highly expressed at the membrane of lamellar bodies in alveolar type II
      cells, in which pulmonary surfactant is stored. ABCA3 gene mutations cause fatal
      surfactant deficiency in newborns. We established HEK293 cells stably expressing
      human ABCA3 and analyzed the function. Exogenously expressed ABCA3 is
      glycosylated and localized at the intracellular vesicle membrane. ABCA3 is
      efficiently photoaffinity labeled by 8-azido-[alpha(32)P]ATP, but not by 8-azido
      [gamma(32)P]ATP, when the membrane fraction is incubated in the presence of
      orthovanadate. Photoaffinity labeling of ABCA3 shows unique metal ion-dependence
      and is largely reduced by membrane pretreatment with 5% methyl-beta-cyclodextrin,
      which depletes cholesterol. Electron micrographs show that HEK293/hABCA3 cells
      contain multivesicular, lamellar body-like structures, which do not exist in
      HEK293 host cells. Some fuzzy components such as lipids accumulate in the
      vesicles. These results suggest that ABCA3 shows ATPase activity, which is
      induced by lipids, and may be involved in the biogenesis of lamellar body-like
      structures.

PMID- 15465013
TI  - Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to
      deplete ATP.
AB  - A common feature of many advanced cancers is their enhanced capacity to
      metabolize glucose to lactic acid. In a challenging study designed to assess
      whether such cancers can be debilitated, we seeded hepatocellular carcinoma cells
      expressing the highly glycolytic phenotype into two different locations of young
      rats. Advanced cancers (2-3cm) developed and were treated with the alkylating
      agent 3-bromopyruvate, a lactate/pyruvate analog shown here to selectively
      deplete ATP and induce cell death. In all 19 treated animals advanced cancers
      were eradicated without apparent toxicity or recurrence. These findings attest to
      the feasibility of completely destroying advanced, highly glycolytic cancers.

PMID- 15465014
TI  - Hepatocyte growth factor induces angiogenesis in injured lungs through mobilizing
      endothelial progenitor cells.
AB  - Circulating endothelial progenitor cells (EPCs) play a pivotal role in
      angiogenesis. Hepatocyte growth factor (HGF) is known to induce proliferation and
      motility in endothelial cells, and to play a role in mitogenic and morphogenic
      actions. However, the role of HGF in EPC mobilization has not been clearly
      described yet. We investigated the effect of HGF on mobilizing EPCs and on
      angiogenesis in elastase-induced lung injury. HGF significantly increased the
      triple-positive (Sca-1(+), Flk-1(+), and c-kit(+)) fraction in peripheral
      mononuclear cells in mice. The bone marrow-derived cells were recruited into the
      injured lungs, where they differentiated to capillary endothelial cells. HGF
      induced proliferation of both bone marrow-derived and resident endothelial cells
      in the alveolar wall. In conclusion, the present study suggests that HGF induces
      EPC mobilization from the bone marrow and enhances the proliferation of
      endothelial cells in vivo. These complex effects induced by HGF orchestrate
      pulmonary regeneration in emphysematous lung parenchyma.

PMID- 15465015
TI  - Topogenesis of NHE1: direct insertion of the membrane loop and sequestration of
      cryptic glycosylation and processing sites just after TM9.
AB  - Multispanning membrane proteins are synthesized by membrane-bound ribosomes and
      integrated into the endoplasmic reticulum membrane cotranslationally. To uncover
      the topogenic process of membrane loop, of which both ends are in the same side
      of the membrane, we examined topogenesis of a relatively hydrophobic lumenal loop
      segment (H10 segment) between TM9 and TM10 of human Na(+)/H(+) exchanger isoform
      1 using an in vitro expression system. The H10 segment was translocated through
      the membrane. Any potential sites created within the H10 segment were not
      glycosylated. Just after TM9, there are potential glycosylation and signal
      peptidase processing sites. When the reporter domain of prolactin was fused at
      the position preceding the H10 segment, these sites were modified by the enzymes,
      while they were not modified in the original molecule. Thus, we concluded that
      the H10 segment was translocated through the membrane and directly inserted into
      the membrane and that its membrane insertion caused sequestration of the
      preceding processing and glycosylation sites from the lumenal modifying enzymes.
      This topogenic process shows clear contrast to that of pore loops of K(+)
      channels, which are once exposed in the lumen and accessible to glycosylation
      enzyme.

PMID- 15465017
TI  - Involvement of Rab27 in antigen-induced histamine release from rat basophilic
      leukemia 2H3 cells.
AB  - The Rab family small G proteins regulate discrete steps in vesicular transport
      pathways. Recent studies indicate that one member of the Rab family, Rab27A,
      regulates the transport of lysosome-related organelles, such as melanosome
      distribution in melanocytes, lytic granule release in cytotoxic T cells, and
      dense granule release in platelets. Here, we have examined the involvement of
      Rab27A in the exocytic transport of another lysosome-related organelle, the
      basophilic secretory granule, in basophils. We have found that Rab27A locates on
      basophilic secretory granules containing histamine in rat basophilic leukemia
      (RBL) 2H3 cells. In addition, exogenous expression of dominant active Rab27A
      reduces antigen-induced histamine release from the cells. We have moreover
      identified Munc13-4 as a Rab27A target using a CytoTrap system and found that
      exogenous expression of Munc13-4 affects antigen-induced histamine release from
      RBL-2H3 cells. These results demonstrate that Rab27A plays a crucial role in
      antigen-induced histamine release from RBL-2H3 cells.

PMID- 15465016
TI  - Post-translational modifications in the survival motor neuron protein.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by
      a progressive loss of the spinal motoneurons. The SMA-determining gene has been
      termed survival motor neuron (SMN) and is deleted or mutated in over 98% of
      patients. The encoded gene product is a protein expressed as different isoforms.
      In particular, we showed that the rat SMN cDNA produces two isoforms with M(r) of
      32 and 35kDa, both localized in nuclear coiled bodies, but the 32kDa form is also
      cytoplasmic, whereas the 35kDa form is also microsomal. To determine the
      molecular relationship between these two isoforms and potential post
      translational modifications, we performed transfection experiments with a double
      tagged rat SMN. Immunoblot and immunostaining studies demonstrated that the 32kDa
      SMN isoform derives from the full length 35kDa, through a proteolytic cleavage at
      the C-terminal. Furthermore, the 35kDa SMN isoform is physiologically
      phosphorylated in vivo. This may modulate its interaction with molecular
      partners, either proteins or nucleic acids.

PMID- 15465018
TI  - Molecular properties of Zic4 and Zic5 proteins: functional diversity within Zic
      family.
AB  - The Zic-family proteins control various developmental processes. Previous studies
      have shown that Zic1, Zic2, and Zic3 can act as transcriptional regulators, and
      that their functions are repressed by I-mfa, which has been identified as a
      repressor for basic helix-loop-helix-type transcriptional factors. Here, we
      investigated the molecular properties of the Zic4 and Zic5 proteins. Zic4/Zic5
      showed DNA-binding activity to the Gli-binding sequence, similar to
      Zic1/Zic2/Zic3 proteins. However, Zic4/Zic5 did not exhibit any significant
      transcriptional activation ability nor they bind to I-mfa differently from
      Zic1/Zic2/Zic3. The nuclear localization of Zic4/Zic5 was not affected by the
      presence of the I-mfa protein, whereas the Zic1/Zic2/Zic3 proteins were
      translocated to the cytoplasmic compartment in the presence of I-mfa. The
      difference may be attributable to the dissimilarity of the N-terminal region
      between the Zic1/Zic2/Zic3 and Zic4/Zic5 proteins, since the binding of the
      Zic1/Zic2/Zic3 proteins to I-mfa occurs through their N-terminal regions.

PMID- 15465019
TI  - Phosphorylation of mouse LASP-1 on threonine 156 by cAMP- and cGMP-dependent
      protein kinase.
AB  - LIM and SH3 domain protein (LASP-1) is a specific focal adhesion protein involved
      in cell migration. Overlay studies demonstrate that LASP-1 directly binds to the
      proline-rich domains of zyxin, lipoma preferred partner (LPP), and vasodilator
      stimulated phosphoprotein (VASP), with zyxin being the most prominent interacting
      partner. Despite the LIM/zinc-finger domain, hypothesized to be involved in
      homodimerization, LASP-1 exists as a monomer. In vitro phosphorylation of
      recombinant mouse LASP-1 by cAMP- and cGMP-dependent protein kinase (PKA and PKG,
      respectively) occurs at serine 61, serine 99, and threonine 156 whereas in intact
      cells mouse LASP-1 is phosphorylated only at threonine 156. This site is
      different from the known in vivo phosphorylation sites in human (serine 146) and
      rabbit (serine 99 and serine 146). Nevertheless, immunofluorescence of LASP-1 in
      human and mouse mesangial cells revealed no difference in subcellular
      distribution. Exposure of the cells to forskolin induced a translocation of both,
      human and mouse LASP-1, from the focal contacts to the cell interior without
      affecting F-actin structure. Immunoblotting of LASP-1 in various mouse and human
      tissues detected a similar prominent expression in non-muscle tissue. Altogether,
      our data suggest so far no functional differences between human and mouse LASP-1.

PMID- 15465020
TI  - Chemokine changes during oral wound healing.
AB  - The oral mucosa is susceptible to tissue injury from many causes, including
      infection, autoimmune disorders, surgical and accidental trauma, and gingival and
      periodontal inflammation; however, little is known about the events that
      influence wound healing in the mouth. Recent studies in non-oral tissues have
      implicated immune system-derived factors, in particular chemokines, in the wound
      healing process. Tissues from mice with experimental gingival wounds were studied
      for expression of genes for four chemokine ligands or receptors (CCL19, CCL20,
      CCL25, and CCR5) that are important in leukocyte trafficking or inflammation.
      Notably, during the peak phase of wound healing, chemokine gene expression was up
      regulated for CCL19, CCL20, and CCL25, and down-regulation of CCR5, suggesting an
      orchestrated process of chemokine-mediated recruitment or retention of
      lymphocytes and macrophages into wound areas, while simultaneously suppressing a
      potentially adverse inflammatory response. These findings have implications for
      developing therapeutic strategies aimed at promoting more effective tissue
      healing at oral surfaces.

PMID- 15465021
TI  - Akt plays a central role in the anti-apoptotic effect of estrogen in endothelial
      cells.
AB  - Estrogen has been reported to inhibit apoptosis in vascular endothelial cells.
      However, its precise mechanism still remains to be elucidated. Here we determined
      the role of Akt in the anti-apoptotic effect of estrogen. 17Beta-estradiol
      prevented the apoptosis induced by TNF-alpha in bovine aortic endothelial cells,
      as evaluated by double staining with fluorescein isothiocyanate-conjugated
      annexin V and propidium iodide. Introducing a dominant negative mutant of Akt by
      using a cell-penetrating peptide of Tat protein inhibited the anti-apoptotic
      effect of estrogen in a concentration-dependent manner, and resulted in the
      complete inhibition of the anti-apoptotic effect of 17beta-estradiol at 1nM and
      higher concentrations. The dominant negative mutant without the cell-penetrating
      peptide and Tat peptide-conjugated protein A had no effect. The intracellular
      protein transduction was confirmed by immunoblot analysis. Our observations thus
      provide first direct evidence that Akt plays a central role in the anti-apoptotic
      effect of estrogen in vascular endothelial cells.

PMID- 15465022
TI  - Reporter gene stimulation by MIDA1 through its DnaJ homology region.
AB  - MIDA1 was reported as a protein that can associate with Id1. Its N-terminus has
      homology to Z-DNA binding protein, Zuotin, that contains DnaJ motif, considered
      to interact with Hsp70s, and Id binding domain. In the present study, we found
      that MIDA1 stimulates the transcription of the co-transfected genes. This
      stimulation was independent of promoter specificity because it was observed in
      various transfected genes. MIDA1 enhanced formation of DNA-protein complexes with
      E-box or TATA box without its direct binding to DNA. Analysis with deletion
      mutants of MIDA1 showed that the short protein fragment containing DnaJ motif
      within Zuotin homology region is sufficient for the stimulation of transcription
      and we demonstrated that MIDA1 associates with Hsp70. These data suggest
      involvement of MIDA1 in the stimulation of transcription in concert with
      Hsp70/Hsc70 molecular chaperones, thus providing a link between Hsp70/Hsc70
      molecular chaperones and components of the transcriptional machinery.

PMID- 15465023
TI  - Molecular cloning and tissue-specific expression analysis of mouse spinesin, a
      type II transmembrane serine protease 5.
AB  - We have previously reported novel serine proteases isolated from cDNA libraries
      of the human and mouse central nervous system (CNS) by PCR using degenerate
      oligodeoxyribonucleotide primers designed on the basis of the serine protease
      motifs, AAHC and DSGGP. Here we report a newly isolated serine protease from the
      mouse CNS. This protease is homologous (77.9% identical) to human spinesin type
      II transmembrane serine protease 5. Mouse spinesin (m-spinesin) is also composed
      of (from the N-terminus) a short cytoplasmic domain, a transmembrane domain, a
      stem region containing a scavenger-receptor-like domain, and a serine protease
      domain, as is h-spinesin. We also isolated type 1, type 2, and type 3 variant
      cDNAs of m-spinesin. Full-length spinesin (type 4) and type 3 contain all the
      domains, whereas type 1 and type 2 variants lack the cytoplasmic, transmembrane,
      and scavenger-receptor-like domains. Subcellular localization of the variant
      forms was analyzed using enhanced green fluorescent protein (EGFP) fusion
      proteins. EGFP-type 4 fusion protein was predominantly localized to the ER, Golgi
      apparatus, and plasma membrane, whereas EGFP-type 1 was localized to the
      cytoplasm, reflecting differential classification of m-spinesin variants into
      transmembrane and cytoplasmic types. We analyzed the distribution of m-spinesin
      variants in mouse tissues, using RT-PCR with variant-specific primer sets.
      Interestingly, transmembrane-type spinesin, types 3 and 4, was specifically
      expressed in the spinal cord, whereas cytoplasmic type, type 1, was expressed in
      multiple tissues, including the cerebrum and cerebellum. Therefore, m-spinesin
      variants may have distinct biological functions arising from organ-specific
      variant expression.

PMID- 15465024
TI  - Effect of hematopoietic cytokines on renal function in cisplatin-induced ARF in
      mice.
AB  - In this study, the effect of hematopoietic cytokines, i.e., granulocyte-colony
      stimulating factor (G-CSF), stem cell factor (SCF), and granulocyte-macrophage
      colony stimulating factor (GM-CSF), on renal function was studied in cisplatin
      induced acute renal failure in mice. Treatment with G-CSF significantly
      ameliorated both BUN and serum creatinine increase induced by cisplatin
      administration with concomitant alleviation in the degree of necrotic change,
      enhancement in DNA synthesis, and decrease in apoptosis of renal tubular cells.
      There was no significant change observed among these parameters following
      treatment with SCF or with GM-CSF. Serum hepatocyte growth factor level was
      significantly lower in mice treated with cisplatin and G-CSF compared with that
      in those treated with cisplatin only. In conclusion, G-CSF, but not SCF or GM
      CSF, acts to accelerate regeneration and prevent apoptosis of renal tubular
      epithelial cells and leads to reduced renal injury in cisplatin-induced acute
      renal failure in mice.

PMID- 15465025
TI  - Potent stimulation of gene expression by histone deacetylase inhibitors on
      transiently transfected DNA.
AB  - Transcription activity of chromatin is associated with histone acetylation which
      is regulated by recruitment of histone acetyltransferases and deacetylases (HDAC)
      to specific chromatin regions. We have tested how expression of a transfected or
      stably introduced gene correlates with histone acetylation. Our results
      demonstrate that expression of transiently transfected green fluorescence protein
      (GFP) genes is significantly enhanced by HDAC inhibitors. Although HDAC treatment
      did not induce noticeable changes in the chromatin structure of genomic DNA,
      chromatin immunoprecipitation showed that more transiently transfected DNA is
      assembled into chromatin containing acetylated histones in HDAC inhibitor treated
      cells when compared to untreated cells. For stably integrated GFP, the expression
      response to HDAC inhibitors varies between independent stable cell lines.
      However, there was no difference in histone acetylation associated with the
      integrated transgene between HDAC inhibitor responsive and non-responsive cells.
      Furthermore, the overall enhancement of transgene expression by HDAC inhibitors
      was not as pronounced as in transiently transfected cells.

PMID- 15465026
TI  - STAT 5 activators can replace the requirement of FBS in the adipogenesis of 3T3
      L1 cells.
AB  - The 3T3-L1 cells differentiate into fat cells that have many properties of native
      adipocytes including: substantial lipid accumulation, insulin sensitivity, and
      the ability to secrete endocrine hormones. A substantial expense in using these
      cells is fetal bovine serum (FBS), a critical component of efficient
      adipogenesis. Our recent studies on STAT 5 proteins have revealed that these
      transcription factors are phosphorylated and translocate to the nucleus
      immediately after the initiation of differentiation. Studies by several other
      laboratories also suggest that STAT 5 proteins can have pro-adipogenic
      properties. Growth hormone (GH) and prolactin (PRL) are both potent activators of
      STAT 5A and STAT 5B proteins. Since, FBS has high concentrations of GH; we
      examined the ability of GH to replace FBS as a component of the differentiation
      cocktail for 3T3-L1 cells. Our studies revealed that FBS was not required for the
      adipogenesis of 3T3-L1 cells if GH or PRL was added to the differentiation
      cocktail. Adipogenesis was judged by Oil Red O staining and expression of
      adipocyte marker genes. Hence, we have developed a substantially less expensive
      method for differentiating 3T3-L1 cells without FBS, thiazolidinediones, or
      expensive cytokines.

PMID- 15465027
TI  - Sequence analysis of the complete mitochondrial genome in patients with
      mitochondrial encephaloneuromyopathies lacking the common pathogenic DNA
      mutations.
AB  - The purpose of this study was to identify novel mitochondrial deoxyribonucleic
      acid (mtDNA) mutations in a series of patients with clinical and/or morphological
      features of mitochondrial dysfunction, but still no genetic diagnosis. A
      heterogeneous group of clinical disorders is caused by mutations in mtDNA that
      damage respiratory chain function of cell energy production. We developed a
      method to systematically screen the entire mitochondrial genome. The sequence
      data were obtained with a rapid automated system. In the six mitochondrial
      genomes analysed we found 20 variants of the revised Cambridge reference sequence
      [Nat. Genet. 23 (1999) 147]. In skeletal muscle nineteen novel mtDNA variants
      were homoplasmic, suggesting secondary pathogenicity or co-responsibility in
      determination of the disease. In one patient we identified a novel heteroplasmic
      mtDNA mutation which presumably has a pathogenic role. This screening is
      therefore useful to extend the mtDNA polymorphism database and should facilitate
      definition of disease-related mutations in human mtDNA.

PMID- 15465028
TI  - Stable suppression of MDR1 gene expression and function by RNAi in Caco-2 cells.
AB  - Vector-based RNAi was used to establish a stable Caco-2 cell line with a
      persistent knockdown of multidrug resistant gene 1 (MDR1) and P-glycoprotein (P
      gp). Several positive clones were collected, many of which showed significantly
      reduced levels of MDR1 mRNA and P-gp compared to wt Caco-2 cells. Selected clones
      were sub-cultivated for six passages and real-time PCR showed that MDR1
      expression remained significantly reduced (up to 96%) over this period of time.
      RNAi-MDR1 clones frozen long term also kept their low MDR1 expression levels when
      re-cultured. Permeability studies were performed across RNAi-MDR1 clone cell
      monolayers, and the efflux of cyclosporine A, digoxin, vinblastine, and
      vincristine showed 58%, 61%, 91%, and 78% decrease in active transport,
      respectively, compared to wt Caco-2 cells. This stably modified Caco-2 cell line
      provides a novel tool for studies on MDR1 and other ABC transporter protein gene
      cellular functions.

PMID- 15465029
TI  - Brn-3c (POU4F3) regulates BDNF and NT-3 promoter activity.
AB  - Brn-3c is a transcription factor necessary for maturation and survival of hair
      cells in the inner ear. Mutations in Brn-3c are associated with deafness in mice
      and with hearing loss in humans. Mice lacking Brn-3c also show reduced
      innervation and loss of sensory neurons presumed to be an indirect effect of hair
      cell loss potentially through lower BDNF and NT-3 expression. Using transient
      transfection assays we show that Brn-3c is capable of activating both BDNF and NT
      3 promoters in inner ear sensory epithelial cell lines. In vitro analysis shows
      that Brn-3c binds to specific elements within the promoters of both genes and
      these elements are sufficient to confer Brn-3c regulation on a heterologous
      promoter. Additionally, BDNF expression is reduced in the inner ear of a Brn-3c
      mutant mouse during embryogenesis. Our data suggest that Brn-3c may play a role
      in regulating neurotrophin gene expression in the inner ear.

PMID- 15465030
TI  - MAP kinase phosphorylation of plant profilin.
AB  - Profilin is a small actin-binding protein and is expressed at high levels in
      mature pollen where it is thought to regulate actin filament dynamics upon pollen
      germination and tube growth. The majority of identified plant profilins contain a
      MAP kinase phosphorylation motif, P-X-T-P, and a MAP kinase interaction motif
      (KIM). In in vitro kinase assays, the tobacco MAP kinases p45(Ntf4) and SIPK,
      when activated by the tobacco MAP kinase kinase NtMEK2, can phosphorylate the
      tobacco profilin NtProf2. Mutagenesis of the threonine residue in this motif
      identified it as the site of MAP kinase phosphorylation. Fractionation of tobacco
      pollen extracts showed that p45(Ntf4) is found exclusively in the high-speed
      pellet fraction while SIPK and profilin are predominantly cytosolic. These data
      identify one of the first substrates to be directly phosphorylated by MAP kinases
      in plants.

PMID- 15465031
TI  - Functional diversity of cytochrome P450s of the white-rot fungus Phanerochaete
      chrysosporium.
AB  - The functional diversity of cytochrome P450s (P450s) of the white-rot
      basidiomycete, Phanerochaete chrysosporium, was studied. A series of compounds
      known to be P450 substrates of other organisms were utilized for metabolic
      studies of P. chrysosporium. Metabolic conversions of benzoic acid, camphor, 1,8
      cineol, cinnamic acid, p-coumaric acid, coumarin, cumene, 1,12-dodecanediol, 1
      dodecanol, 4-ethoxybenzoic acid, and 7-ethoxycoumarin were observed with P.
      chrysosporium for the first time. 1-Dodecanol was hydroxylated at seven different
      positions to form 1,12-, 1,11-, 1,10-, 1,9-, 1,8-, 1,7-, and 1,6-dodecandiols.
      The effect of piperonyl butoxide, a P450 inhibitor, on the fungal conversion of 1
      dodecanol was also investigated, indicating that hydroxylation reactions of 1
      dodecanol were inhibited by piperonyl butoxide in a concentration-dependent
      manner. With 11 substrates, 23 hydroxylation reactions and 2 deethylation
      reactions were determined and 6 products were new with the position of hydroxyl
      group incorporated. In conclusion, fungal P450s were shown to have diverse and
      unique functions.

PMID- 15465032
TI  - Sumoylation increases HIF-1alpha stability and its transcriptional activity.
AB  - HIF-1 is closely involved in various biological processes, including
      angiogenesis, energy metabolism, and cell survival. HIF-1 consists of an oxygen
      sensitive HIF-1alpha and oxygen-insensitive HIF-1beta. Oxygen-sensitive HIF
      1alpha is subjected to post-translational modifications such as hydroxylation,
      ubiquitination, and acetylation, which are related to the regulation of its
      stability. In this present study, we found that the ectopic expression of SUMO-1
      increased HIF-1alpha stability by the co-transfection study with HIF-1alpha and
      SUMO-1. Furthermore, the ectopic expression of SUMO-1 enhanced the
      transcriptional activity of HIF-1alpha. In the subsequent immunoprecipitation
      assay, SUMO-1 was co-immunoprecipitated with HIF-1alpha, implying that HIF-1alpha
      is covalently modified by SUMO-1. Thereafter, using a series of lysine mutants in
      the ODD domain, we found that HIF-1alpha was sumoylated at Lys(391) and Lys(477),
      suggesting that sumoylation at these two lysine residues enhances HIF-1alpha
      stability by possibly modulating other post-translational modifications.
      Altogether, we demonstrate that HIF-1alpha is upregulated through SUMO-1
      modification at Lys(391)/Lys(477) residues, which may stabilize HIF-1alpha and
      enhance its transcriptional activity.

PMID- 15465033
TI  - The biochemical activation of T-type Ca2+ channels in HEK293 cells stably
      expressing alpha1G and Kir2.1 subunits.
AB  - In order to investigate the currently unknown cellular signaling pathways of T
      type Ca(2+) channels, we decided to construct a new cell line which would stably
      express alpha(1G) and Kir2.1 subunits in HEK293 cells (HEK293/alpha(1G)/Kir2.1).
      Compared to cells which only expressed alpha(1G) (HEK293/alpha(1G)),
      HEK293/alpha(1G)/Kir2.1 cells produced an enormous inward rectifying current
      which was blocked by external Ba(2+) and Cs(+) in a concentration-dependent
      manner. The expression of Kir2.1 channels contributed significantly to the shift
      of membrane potential from -12.2+/-2.8 to -57.3+/-3.7mV. However, biophysical and
      pharmacological properties of alpha(1G)-mediated Ca(2+) channels remained
      unaffected by the expression of Kir2.1 subunits, except for the enlarging of the
      window current region. Biochemical activation of alpha(1G) channels using 150mM
      KCl brought about an increase in [Ca(2+)](i), which was blocked by mibefradil,
      the T-type Ca(2+) channel blocker. These data suggest that the
      HEK293/alpha(1G)/Kir2.1 cell line would have potential uses in the study of T
      type Ca(2)(+) channel-mediated signaling pathways and possibly useful in the
      development of new therapeutic drugs associated with T-type Ca(2)(+) channels.

PMID- 15465034
TI  - Hepatic flavin-containing monooxygenase activity attenuated by cGMP-independent
      nitric oxide-mediated mRNA destabilization.
AB  - To identify the novel mechanism by which nitric oxide (NO) suppresses flavin
      containing monooxygenase (FMO) activity in endotoxemic rat livers, NO
      overproducing conditions were induced in primary cultured rat hepatocytes by
      treatment with a mixture (LCM) of lipopolysaccharide and proinflammatory
      cytokines (IL-1beta, TNF-alpha, and IFN-gamma), or by the addition of a pure NO
      donor, spermine-NONOate. mRNA levels of the major hepatic form, FMO1, decreased
      via a cGMP-independent destabilizing effect of NO rather than by decreased
      transcription. The decrease in the mRNA levels caused by LCM-induced inducible NO
      synthase (iNOS) was completely blocked by co-treatment with aminoguanidine, a
      selective iNOS inhibitor. Furthermore, spermine-NONOate, but not the cGMP analog,
      8-bromo-cGMP, dose- and time-dependently attenuated FMO1 mRNA stability in
      actinomycin-D-pretreated cells, resulting in decreases in protein levels and
      biochemical activity. These results suggest that NO acts directly in a cGMP
      independent mechanism by decreasing the half-life of FMO1 mRNA, thereby inducing
      impairment of FMO-related functions in endotoxemia.

PMID- 15465035
TI  - The inhibitory effect of sodium nitroprusside on HIF-1 activation is not
      dependent on nitric oxide-soluble guanylyl cyclase pathway.
AB  - Adaptation to hypoxia and maintenance of O(2) homeostasis involve a wide range of
      responses that occur at different organizational levels in the body. One of the
      most important transcription factors that activate the expression of O(2)
      regulated genes is hypoxia-inducible factor 1 (HIF-1). Nitric oxide (NO) mediates
      a variety of biological effects including relaxation of blood vessels and
      cytotoxicity of activated macrophages. We investigated the effect of the
      clinically used nitrates nitroglycerin (NTG), isosorbide dinitrate (ISDN), and
      sodium nitroprusside (SNP) on HIF-1-mediated transcriptional responses to
      hypoxia. We demonstrate that among the three nitrates, only SNP inhibits HIF-1
      activation in response to hypoxia. In contrast, NTG or ISDN does not affect HIF-1
      activity. SNP inhibits the accumulation of HIF-1alpha, the regulatory subunit of
      HIF-1, and the transcriptional activation of HIF-1alpha via a mechanism that is
      not dependent on either NO or soluble guanylate cyclase.

PMID- 15465036
TI  - Transforming growth factor-beta induces the expression of ANF and hypertrophic
      growth in cultured cardiomyoblast cells through ZAK.
AB  - Transforming growth factor-beta (TGF-beta) has been associated with the onset of
      cardiac cell hypertrophy, but the mechanisms underlying this dissociation are not
      completely understood. By a previous study, we investigated the involvement of a
      MAP3K, ZAK, which in cultured H9c2 cardiac cells is a positive mediator of cell
      hypertrophy. Our results showed that expression of a dominant-negative form of
      ZAK inhibited the characteristic TGF-beta-induced features of cardiac
      hypertrophy, including increased cell size, elevated expression of atrial
      natriuretic factor (ANF), and increased organization of actin fibers.
      Furthermore, dominant-negative MKK7 effectively blocked both TGF-beta-and ZAK
      induced ANF expression. In contrast, a JNK/SAPK specific inhibitor, sp600125, had
      little effect on TGF-beta- or ZAK-induced ANF expression. Our findings suggest
      that a ZAK mediates TGF-beta-induced cardiac hypertrophic growth via a novel TGF
      beta signaling pathway that can be summarized as TGF-beta>ZAK>MKK7>ANF.

PMID- 15465037
TI  - The coiled-coil domain of TRAF6 is essential for its auto-ubiquitination.
AB  - Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a crucial signaling
      transducer that regulates a diverse array of physiological processes, including
      adaptive immunity, innate immunity, and bone metabolism. Importantly, it is
      essential for activating NF-kappaB signaling pathway in response to interleukin-1
      and Toll-like receptor ligands. Previously, we characterized TRAF6 to be a
      ubiquitin ligase. In combination with the ubiquitin conjugating enzyme complex
      Ubc13/Uev1A, TRAF6 could catalyze the formation on itself of unique Lys-63 linked
      polyubiquitin chain that positively regulated NF-kappaB signaling pathway.
      However, it remains unknown how this auto-ubiquitination process is regulated. In
      this study, we found that the coiled-coil domain of TRAF6 was essential for its
      auto-ubiquitination and activating NF-kappaB signaling pathway. This domain
      served not as the specific target where the polyubiquitin chain was linked, but
      as a specific bridge to recruit Ubc13/Uev1A.

PMID- 15465038
TI  - TIMP-1 stimulates proliferation of human aortic smooth muscle cells and Ras
      effector pathways.
AB  - Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a multifunctional protein,
      which is found in most tissues and body fluids. Here, we demonstrated that
      recombinant TIMP-1 but not the synthetic matrix metalloproteinase inhibitor,
      GM6001, stimulated proliferation of human aortic smooth muscle cells (AoSMC) in a
      dose-dependent manner. The mitogenic effect was associated with activation of
      Ras, increased phosphorylation of ERK, and stimulation of cyclin D1 expression.
      The phosphatidylinositol 3-kinase (PI3K) signaling pathway was also involved
      since the PI3K inhibitor, LY294002, abolished the TIMP-1-mediated growth
      stimulation. These data suggest that TIMP-1 activates Ras, which then turns on
      the ERK and PI3K signaling pathways to promote cell cycle progression of the
      AoSMC.

PMID- 15465039
TI  - Accelerated CuZn-SOD-mediated oxidation and reduction in the presence of hydrogen
      peroxide.
AB  - Copper, zinc-superoxide dismutase (CuZn-SOD) is a cytosolic, antioxidant enzyme
      that scavenges potentially damaging superoxide radical (()O(2)(-)). Under the
      proper conditions, CuZn-SOD also catalyzes the oxidation and reduction of certain
      small molecules. Here, we demonstrate that increased exposure to hydrogen
      peroxide (H(2)O(2)), a by-product of the ()O(2)(-) scavenging reaction,
      dramatically increases the ability of CuZn-SOD to oxidize melatonin and reduce S
      nitrosoglutathione (GSNO). After a 15min in vitro incubation with CuZn-SOD and
      1mM H(2)O(2), 76% of the melatonin was oxidized, compared to 52% with 0.25mM
      H(2)O(2), and just 9% without H(2)O(2). Pre-incubation with 1mM H(2)O(2) resulted
      in a 100% increase in the rate of GSNO breakdown by CuZn-SOD in the presence of
      glutathione (GSH) compared to untreated CuZn-SOD. Collectively, these data
      suggest that even small increases in intracellular H(2)O(2) levels may result in
      the oxidation and/or reduction of small molecules critical for proper cellular
      function.

PMID- 15465040
TI  - Metabolism of vitamin D by human microsomal CYP2R1.
AB  - The activation of vitamin D requires 25-hydroxylation in the liver and 1alpha
      hydroxylation in the kidney. However, it remains unclear which enzyme is relevant
      to vitamin D 25-hydroxylation. Recently, human CYP2R1 has been reported to be a
      potential candidate for a hepatic vitamin D 25-hydroxylase. Thus, vitamin D
      metabolism by CYP2R1 was compared with human mitochondrial CYP27A1, which used to
      be considered a physiologically important vitamin D(3) 25-hydroxylase. A clear
      difference was observed between CYP2R1 and CYP27A1 in the metabolism of vitamin
      D(2). CYP2R1 hydroxylated vitamin D(2) at the C-25 position while CYP27A1
      hydroxylated it at positions C-24 and C-27. The K(m) and k(cat) values for the
      CYP2R1-dependent 25-hydroxylation activity toward vitamin D(3) were 0.45microM
      and 0.97min(-1), respectively. The k(cat)/K(m) value of CYP2R1 was 26-fold higher
      than that of CYP27A1. These results strongly suggest that CYP2R1 plays a
      physiologically important role in the vitamin D 25-hydroxylation in humans.

PMID- 15465041
TI  - Lysophosphatidic acid is a mediator of Trp-Lys-Tyr-Met-Val-d-Met-induced calcium
      influx.
AB  - Intracellular calcium (Ca(2+)) homeostasis is very strictly regulated, and the
      activation of G-protein-coupled receptor (GPCR) can cause two different calcium
      changes, intracellular calcium release, and calcium influx. In this study, we
      investigated the possible role of lysophosphatidic acid (LPA) on GPCR-induced
      Ca(2+) signaling. The addition of exogenous LPA induced dramatic Ca(2+) influx
      but not intracellular Ca(2+) release in U937 cells. LPA-induced Ca(2+) influx was
      not affected by pertussis toxin and phospholipase C inhibitor (U73122), ruling
      out the involvement of pertussis toxin-sensitive G-proteins, and phospholipase C.
      Stimulation of U937 cells with Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), which binds to
      formyl peptide receptor like 1, enhanced phospholipase A(2) and phospholipase D
      activation, indicating LPA formation. The inhibition of LPA synthesis by
      phospholipase A(2)-specific inhibitor (MAFP) or n-butanol significantly inhibited
      WKYMVm-induced Ca(2+) influx, suggesting a crucial role for LPA in the process.
      Taken together, we suggest that LPA mediates WKYMVm-induced Ca(2+) influx.

PMID- 15465042
TI  - Novel protein--protein interaction between Escherichia coli SoxS and the DNA
      binding determinant of the RNA polymerase alpha subunit: SoxS functions as a co
      sigma factor and redeploys RNA polymerase from UP-element-containing promoters to
      SoxS-dependent promoters during oxidative stress.
AB  - SoxS is the transcription activator of the SoxRS regulon. Despite being
      synthesized de novo in response to oxidative stress and despite the large
      disparity between the number of SoxS binding sites and the number of SoxS
      molecules per cell, SoxS-dependent promoters are rapidly activated after the
      onset of the stress. With the usual recruitment/post-recruitment mechanisms being
      unsuitable for activating gene expression under these conditions, we previously
      proposed that SoxS functions by "pre-recruitment". In pre-recruitment, SoxS forms
      SoxS-RNA polymerase binary complexes, which use the DNA binding properties of
      SoxS and sigma(70) to distinguish SoxS-dependent promoters from housekeeping
      promoters and from the large number of sequence-equivalent but functionally
      irrelevant SoxS binding sites. With previous work in Escherichia coli having
      indicated that the most likely target on RNA polymerase for interaction with SoxS
      is the C-terminal domain of alpha, we investigated the interaction directly with
      the yeast two-hybrid system. We found that SoxS interacts with the alphaCTD and
      that SoxS positive control mutations disrupt the interaction. Moreover, single
      alanine substitutions of the alphaCTD that reduce or enhance SoxS activation in
      E.coli reduce or enhance the interaction between SoxS and the alphaCTD in yeast.
      Significantly, the critical amino acid residues lie in and around the DNA binding
      determinant of the alphaCTD, the first example of an activator contacting this
      determinant. These interactions were confirmed with an affinity immobilization
      assay. Lastly, we found that SoxS induction interferes with utilization of the UP
      element of an rRNA promoter. Thus, by functioning as a co-sigma factor that
      interacts with the DNA binding determinant of the alphaCTD, SoxS diverts RNA
      polymerase from UP-containing promoters to SoxS-activatable promoters.

PMID- 15465043
TI  - Comparison of ligand-induced conformational changes and domain closure
      mechanisms, between prokaryotic and eukaryotic dehydroquinate synthases.
AB  - Dehydroquinate synthase (DHQS) is a potential target for the development of novel
      broad-spectrum antimicrobial drugs, active against both prokaryotes and lower
      eukaryotes. Structures have been reported for Aspergillus nidulans DHQS (AnDHQS)
      in complexes with a range of ligands. Analysis of these AnDHQS structures showed
      that a large-scale domain movement occurs during the normal catalytic cycle, with
      a complex series of structural elements propagating substrate binding-induced
      conformational changes away from the active site to distal locations. Compared to
      corresponding fungal enzymes, DHQS from bacterial species are both mono
      functional and significantly smaller. We have therefore determined the structure
      of Staphylococcus aureus DHQS (SaDHQS) in five liganded states, allowing
      comparison of ligand-induced conformational changes and mechanisms of domain
      closure between fungal and bacterial enzymes. This comparative analysis shows
      that substrate binding initiates a large-scale domain closure in both species'
      DHQS and that the active site stereochemistry, of the catalytically competent
      closed-form enzyme thus produced, is also highly conserved. However, comparison
      of AnDHQS and SaDHQS open-form structures, and analysis of the putative dynamic
      processes by which the transition to the closed-form states are made, shows a far
      lower degree of similarity, indicating a significant structural divergence. As a
      result, both the nature of the propagation of conformational change and the
      mechanical systems involved in this propagation are quite different between the
      DHQSs from the two species.

PMID- 15465044
TI  - Conformational changes induced by nucleotide binding in Cdc6/ORC from Aeropyrum
      pernix.
AB  - Archaea contain one or more proteins with homology to eukaryotic ORC/Cdc6
      proteins. Sequence analysis suggests the existence of at least two subfamilies of
      these proteins, for which we propose the nomenclature ORC1 and ORC2. We have
      determined crystal structures of the ORC2 protein from the archaeon Aeropyrum
      pernix in complexes with ADP or a non-hydrolysable ATP analogue, ADPNP. Between
      two crystal forms, there are three crystallographically independent views of the
      ADP complex and two of the ADPNP complex. The protein molecules in the three
      complexes with ADP adopt very different conformations, while the two complexes
      with ADPNP are the same. These structures indicate that there is considerable
      conformational flexibility in ORC2 but that ATP binding stabilises a single
      conformation. We show that the ORC2 protein can bind DNA, and that this activity
      is associated with the C-terminal domain of the protein. We present a model for
      the interaction of the winged helix (WH) domain of ORC2 with DNA that differs
      from that proposed previously for Pyrobaculum aerophilum ORC/Cdc6.

PMID- 15465045
TI  - Systematic delineation of a calmodulin peptide interaction.
AB  - We present a comprehensive profile of amino acid side-chain constraints in a
      calmodulin (CaM) peptide complex. These data were obtained from the analysis of
      calmodulin binding to an array of all single substitution analogues as well as N-
      and C-terminal truncations of the skMLCK derived M13 peptide ligand. The
      experimentally derived binding data were evaluated with respect to the known 3D
      structure of the CaM/M13 complex. Besides an almost perfect agreement between the
      measured affinities and the structural data, the unexpected high-affine Asn5Ala
      variant of the M13(*) peptide described by Montigiani et al. could be verified.
      In contrast to other reports our data clearly support the postulate of the minor
      and major hydrophobic anchors of this calcium dependent interaction.

PMID- 15465046
TI  - A hydrophobic patch on the flap-tip helix of E.coli RNA polymerase mediates
      sigma(70) region 4 function.
AB  - The Escherichia coli RNA polymerase beta subunit contains a flexible flap domain
      that interacts with region 4 of sigma(70) to position it for recognition of the 
      35 element of promoters. We report that this function depends on a hydrophobic
      patch on one face of the short stretch of alpha helix located at the tip of the
      flap domain, called the flap-tip helix. Disruption of the hydrophobic patch by
      the substitution of hydrophilic or charged amino acids resulted in a loss of the
      interaction between the flap and sigma region 4, as determined by protease
      sensitivity assays, and impaired transcription from -35-dependent promoters. We
      suggest that contact of the flap-tip helix hydrophobic patch to the sigma region
      4 hydrophobic core is essential for stable interaction of the flap-tip helix with
      region 4. This contact allowed region 4.2 recognition of the -35 promoter element
      and appeared to stabilize region 4 interaction with the beta' Zn(2+) binding
      domain. Our studies failed to detect any role for sigma region 1.1 in
      establishing or maintaining the flap-sigma region 4 interaction, consistent with
      recent reports placing sigma region 1.1 in the downstream DNA channel.

PMID- 15465047
TI  - Conservation and developmental control of alternative splicing in maebl among
      malaria parasites.
AB  - Genes of malaria parasites and other unicellular organisms have larger exons with
      fewer and smaller introns than metaozoans. Such differences in gene structure are
      perceived to extend to simpler mechanisms for transcriptional control and mRNA
      processing. Instead, we discovered a surprisingly complex level of post
      transcriptional mRNA processing in analysis of maebl transcripts in several
      Plasmodium species. Mechanisms for internal alternative cis-splicing and exon
      skipping were active in multiple life cycle stages to change exon structure in
      the deduced coding sequence (CDS). The major alternatively spliced transcript
      utilized a less favorable acceptor splice site, which shifted codon triplet usage
      to a different CDS with a hydrophilic C terminus, changing the canonical type I
      membrane MAEBL product to a predicted soluble isoform. We found that
      developmental control of the alternative splicing pattern was distinct from the
      canonical splicing pattern. Western blot analysis indicated that MAEBL expression
      was better correlated with the appearance of the canonical ORF1 transcript.
      Together these data reveal that RNA metabolism in unicellular eukaryotes like
      Plasmodium is more sophisticated than believed and may have a significant role
      regulating gene expression in Plasmodium.

PMID- 15465049
TI  - PilV adhesins of plasmid R64 thin pili specifically bind to the
      lipopolysaccharides of recipient cells.
AB  - IncI1 plasmid R64 encodes type IV pili or thin pili, which contain PilV adhesins.
      The C-terminal segments of PilV adhesins are exchanged into seven types by
      shufflon multiple DNA inversion. PilV adhesins determine recipient specificity in
      R64 liquid matings through the recognition of lipopolysaccharides (LPSs) on the
      surface of recipient cells. Using various waa mutants of Escherichia coli R1 as
      recipient cells, liquid mating experiments suggest that PilVA adhesin recognizes
      the GlcNAc(beta1-3)Glc moiety of E.coli R1 type LPS. The direct binding of PilV
      adhesins to LPSs of the recipient bacterial strains was demonstrated using filter
      overlay assays. The specificity of PilV-LPS binding is in close agreement with
      the recipient specificity determined by R64 liquid matings. The C-terminal
      segments of PilVA, PilVC, PilVC', and PilVD' adhesins were expressed as fusion
      proteins with glutathione-S-transferase (GST). GST-A, GST-C, GST-C', and GST-D'
      proteins bound to their respective LPSs with the specificities identical with
      those determined in the R64 liquid matings, indicating that the C-terminal
      segments of PilV adhesins bind to specific moieties of LPS molecules.

PMID- 15465050
TI  - Relative flexibility of DNA and RNA: a molecular dynamics study.
AB  - State of the art molecular dynamics simulations are used to study the structure,
      dynamics, molecular interaction properties and flexibility of DNA and RNA
      duplexes in aqueous solution. Special attention is paid to the deformability of
      both types of structures, revisiting concepts on the relative flexibility of DNA
      and RNA duplexes. Our simulations strongly suggest that the concepts of
      flexibility, rigidity and deformability are much more complex than usually
      believed, and that it is not always true that DNA is more flexible than RNA.

PMID- 15465051
TI  - Processing of the dual targeted precursor protein of glutathione reductase in
      mitochondria and chloroplasts.
AB  - Pea glutathione reductase (GR) is dually targeted to mitochondria and
      chloroplasts by means of an N-terminal signal peptide of 60 amino acid residues.
      After import, the signal peptide is cleaved off by the mitochondrial processing
      peptidase (MPP) in mitochondria and by the stromal processing peptidase (SPP) in
      chloroplasts. Here, we have investigated determinants for processing of the dual
      targeting signal peptide of GR by MPP and SPP to examine if there is separate or
      universal information recognised by both processing peptidases. Removal of 30 N
      terminal amino acid residues of the signal peptide (GRDelta1-30) greatly
      stimulated processing activity by both MPP and SPP, whereas constructs with a
      deletion of an additional ten amino acid residues (GRDelta1-40) and deletion of
      22 amino acid residues in the middle of the GR signal sequence (GRDelta30-52)
      could be cleaved by SPP but not by MPP. Numerous single mutations of amino acid
      residues in proximity of the cleavage site did not affect processing by SPP,
      whereas mutations within two amino acid residues on either side of the processing
      site had inhibitory effect on processing by MPP with a nearly complete inhibition
      for mutations at position -1. Mutation of positively charged residues in the C
      terminal half of the GR targeting peptide inhibited processing by MPP but not by
      SPP. An inhibitory effect on SPP was detected only when double and triple
      mutations were introduced upstream of the cleavage site. These results indicate
      that: (i) recognition of processing site on a dual targeted GR precursor differs
      between MPP and SPP; (ii) the GR targeting signal has similar determinants for
      processing by MPP as signals targeting only to mitochondria; and (iii) processing
      by SPP shows a low level of sensitivity to single mutations on targeting peptide
      and likely involves recognition of the physiochemical properties of the sequence
      in the vicinity of cleavage rather than a requirement for specific amino acid
      residues.

PMID- 15465048
TI  - High resolution crystal structure of a key editosome enzyme from Trypanosoma
      brucei: RNA editing ligase 1.
AB  - Trypanosomatids are causative agents of several devastating tropical diseases
      such as African sleeping sickness, Chagas' disease and leishmaniasis. There are
      no effective vaccines available to date for treatment of these protozoan
      diseases, while current drugs have limited efficacy, significant toxicity and
      suffer from increasing resistance. Trypanosomatids have several remarkable and
      unique metabolic and structural features that are of great interest for
      developing new anti-protozoan therapeutics. One such feature is "RNA editing", an
      essential process in these pathogenic protozoa. Transcripts for key
      trypanosomatid mitochondrial proteins undergo extensive post-transcriptional RNA
      editing by specifically inserting or deleting uridylates from pre-mature mRNA in
      order to create mature mRNAs that encode functional proteins. The RNA editing
      process is carried out in a approximately 1.6 MDa multi-protein complex, the
      editosome. In Trypanosoma brucei, one of the editosome's core enzymes, the RNA
      editing ligase 1 (TbREL1), has been shown to be essential for survival of both
      insect and bloodstream forms of the parasite. We report here the crystal
      structure of the catalytic domain of TbREL1 at 1.2 A resolution, in complex with
      ATP and magnesium. The magnesium ion interacts with the beta and gamma-phosphate
      groups and is almost perfectly octahedrally coordinated by six phosphate and
      water oxygen atoms. ATP makes extensive direct and indirect interactions with the
      ligase via essentially all its atoms while extending its base into a deep pocket.
      In addition, the ATP makes numerous interactions with residues that are conserved
      in the editing ligases only. Further away from the active site, TbREL1 contains a
      unique loop containing several hydrophobic residues that are highly conserved
      among trypanosomatid RNA editing ligases which may play a role in protein-protein
      interactions in the editosome. The distinct characteristics of the adenine
      binding pocket, and the absence of any close homolog in the human genome, bode
      well for the design of selective inhibitors that will block the essential RNA
      ligase function in a number of major protozoan pathogens.

PMID- 15465052
TI  - The structures of inhibitor complexes of Pyrococcus furiosus phosphoglucose
      isomerase provide insights into substrate binding and catalysis.
AB  - Pyrococcus furiosus phosphoglucose isomerase (PfPGI) is a metal-containing enzyme
      that catalyses the interconversion of glucose 6-phosphate (G6P) and fructose 6
      phosphate (F6P). The recent structure of PfPGI has confirmed the hypothesis that
      the enzyme belongs to the cupin superfamily and identified the position of the
      active site. This fold is distinct from the alphabetaalpha sandwich fold commonly
      seen in phosphoglucose isomerases (PGIs) that are found in bacteria, eukaryotes
      and some archaea. Whilst the mechanism of the latter family is thought to proceed
      through a cis-enediol intermediate, analysis of the structure of PfPGI in the
      presence of inhibitors has led to the suggestion that the mechanism of this
      enzyme involves the metal-dependent direct transfer of a hydride between C1 and
      C2 atoms of the substrate. To gain further insight in the reaction mechanism of
      PfPGI, the structures of the free enzyme and the complexes with the inhibitor, 5
      phospho-d-arabinonate (5PAA) in the presence and absence of metal have been
      determined. Comparison of these structures with those of equivalent complexes of
      the eukaryotic PGIs reveals similarities at the active site in the disposition of
      possible catalytic residues. These include the presence of a glutamic acid
      residue, Glu97 in PfPGI, which occupies the same position relative to the
      inhibitor as that of the glutamate that is thought to function as the catalytic
      base in the eukaryal-type PGIs. These similarities suggest that aspects of the
      catalytic mechanisms of these two structurally unrelated PGIs may be similar and
      based on an enediol intermediate.

PMID- 15465053
TI  - Structural analysis of Arabidopsis thaliana nucleoside diphosphate kinase-2 for
      phytochrome-mediated light signaling.
AB  - In plants, nucleoside diphosphate kinases (NDPKs) play a key role in the
      signaling of both stress and light. However, little is known about the structural
      elements involved in their function. Of the three NDPKs (NDPK1-NDPK3) expressed
      in Arabidopsis thaliana, NDPK2 is involved in phytochrome-mediated signal
      transduction. In this study, we found that the binding of dNDP or NTP to NDPK2
      strengthens the interaction significantly between activated phytochrome and
      NDPK2. To better understand the structural basis of the phytochrome-NDPK2
      interaction, we determined the X-ray structures of NDPK1, NDPK2, and dGTP-bound
      NDPK2 from A.thaliana at 1.8A, 2.6A, and 2.4A, respectively. The structures
      showed that nucleotide binding caused a slight conformational change in NDPK2
      that was confined to helices alphaA and alpha2. This suggests that the presence
      of nucleotide in the active site and/or the evoked conformational change
      contributes to the recognition of NDPK2 by activated phytochrome. In vitro
      binding assays showed that only NDPK2 interacted specifically with the
      phytochrome and the C-terminal regulatory domain of phytochrome is involved in
      the interaction. A domain swap experiment between NDPK1 and NDPK2 showed that the
      variable C-terminal region of NDPK2 is important for the activation by
      phytochrome. The structure of Arabidopsis NDPK1 and NDPK2 showed that the
      isoforms share common electrostatic surfaces at the nucleotide-binding site, but
      the variable C-terminal regions have distinct electrostatic charge distributions.
      These findings suggest that the binding of nucleotide to NDPK2 plays a regulatory
      role in phytochrome signaling and that the C-terminal extension of NDPK2 provides
      a potential binding surface for the specific interaction with phytochromes.

PMID- 15465054
TI  - Structures of unliganded and inhibitor complexes of W168F, a Loop6 hinge mutant
      of Plasmodium falciparum triosephosphate isomerase: observation of an
      intermediate position of loop6.
AB  - The enzymatic reaction of triosephosphate isomerase (TIM) is controlled by the
      movement of a loop (loop6, residues 166-176). Crystal structures of TIMs from a
      variety of sources have revealed that the loop6, which is in an open conformation
      in the unliganded enzyme, adopts a closed conformation in inhibitor complexes. In
      contrast, structures with loop open conformation are obtained in most of the
      complexes of TIM from the malarial parasite Plasmodium falciparum (PfTIM). W168
      is a conserved N-terminal hinge residue, involved in different sets of
      interactions in the "open" and "closed" forms of loop6. The role of W168 in
      determining the loop conformation was examined by structural studies on the
      mutant W168F and its complexes with ligands. The three-dimensional structures of
      unliganded mutant (1.8 A) and complexes with sulfate (2.8 A) and glycerol-2
      phosphate (G2P) (2.8 A) have been determined. Loop6 was found disordered in these
      structures, reflecting the importance of W168 in stabilizing either the open or
      the closed states. Critical sequence differences between the Plasmodium enzyme
      and other TIMs may influence the equilibrium between the closed and open forms.
      Examination of the environment of the loop6 shows that its propensity for the
      open or the closed forms is influenced not only by Phe96 as suggested earlier,
      but also by Asn233, which occurs in the vicinity of the active site. This residue
      is Gly in the other TIM sequences and probably plays a crucial role in the mode
      of ligand binding, which in turn affects the loop opening/closing process in
      PfTIM.

PMID- 15465055
TI  - Substantial energetic improvement with minimal structural perturbation in a high
      affinity mutant antibody.
AB  - Here, we compare an antibody with the highest known engineered affinity (K(d)=270
      fM) to its high affinity wild-type (K(d)=700 pM) through thermodynamic, kinetic,
      structural, and theoretical analyses. The 4M5.3 anti-fluorescein single chain
      antibody fragment (scFv) contains 14 mutations from the wild-type 4-4-20 scFv and
      has a 1800-fold increase in fluorescein-binding affinity. The dissociation rate
      is approximately 16,000 times slower in the mutant; however, this substantial
      improvement is offset somewhat by the association rate, which is ninefold slower
      in the mutant. Enthalpic contributions to binding were found by calorimetry to
      predominate in the differential binding free energy. The crystal structure of the
      4M5.3 mutant complexed with antigen was solved to 1.5A resolution and compared
      with a previously solved structure of an antigen-bound 4-4-20 Fab fragment.
      Strikingly, the structural comparison shows little difference between the two
      scFv molecules (backbone RMSD of 0.6A), despite the large difference in affinity.
      Shape complementarity exhibits a small improvement between the variable light
      chain and variable heavy chain domains within the antibody, but no significant
      improvement in shape complementarity of the antibody with the antigen is observed
      in the mutant over the wild-type. Theoretical modeling calculations show
      electrostatic contributions to binding account for -1.2 kcal/mol to -3.5 kcal/mol
      of the binding free energy change, of which -1.1 kcal/mol is directly associated
      with the mutated residue side-chains. The electrostatic analysis reveals several
      mechanistic explanations for a portion of the improvement. Collectively, these
      data provide an example where very high binding affinity is achieved through the
      cumulative effect of many small structural alterations.

PMID- 15465056
TI  - Quantification of PDZ domain specificity, prediction of ligand affinity and
      rational design of super-binding peptides.
AB  - Transient macromolecular complexes are often formed by protein-protein
      interaction domains (e.g. PDZ, SH2, SH3, WW) which recognize linear sequence
      motifs with in vitro affinities typically in the micromolar range. The analysis
      of the resulting interaction networks requires a quantification of domain
      specificity and selectivity towards all possible ligands with physiologically
      relevant affinity. As representative examples, we determined specificity as a
      function of ligand sequence-dependent affinity contributions by statistical
      analysis of peptide library screens for the AF6, ERBIN and SNA1 (alpha-1
      syntrophin) PDZ domains. For this purpose, the three PDZ domains were first
      screened for binding with a peptide library comprising 6223 human C termini
      created by SPOT synthesis. Based on the detected ligand preferences, we designed
      focused peptide libraries (profile libraries). These libraries were used to
      quantify the affinity contributions of the four C-terminal ligand residues by
      means of ANOVA models (analysis of variance) relating the C-terminal ligand
      sequences to the corresponding dissociation constants. Our models agreed well
      with experimentally determined dissociation constants and allowed us to design
      super binding peptides. The latter were shown experimentally to bind to their
      cognate PDZ domains with the highest affinity. In addition, we determined
      structure-activity relationships and thereby rationalized the position-specific
      affinity contributions. Furthermore, we used the statistical models to predict
      the dissociation constants for the complete ligand sequence space and thus
      determined the specificity overlap for the three investigated PDZ domains ().
      Altogether, we present an efficient method for profiling protein-protein
      interaction domains that provides a biophysical picture of specificity and
      selectivity. This approach allows the rational design of functional experiments
      and provides a basis for simulating interaction networks in the field of systems
      biology.

PMID- 15465058
TI  - Beyond consensus: statistical free energies reveal hidden interactions in the
      design of a TPR motif.
AB  - Consensus design methods have been used successfully to engineer proteins with a
      particular fold, and moreover to engineer thermostable exemplars of particular
      folds. Here, we consider how a statistical free energy approach can expand upon
      current methods of phylogenetic design. As an example, we have analyzed the
      tetratricopeptide repeat (TPR) motif, using multiple sequence alignment to
      identify the significance of each position in the TPR. The results provide
      information above and beyond that revealed by consensus design alone, especially
      at poorly conserved positions. A particularly striking finding is that certain
      residues, which TPR-peptide co-crystal structures show are in direct contact with
      the ligand, display a marked hypervariability. This suggests a novel means of
      identifying ligand-binding sites, and also implies that TPRs generally function
      as ligand-binding domains. Using perturbation analysis (or statistical coupling
      analysis), we examined site-site interactions within the TPR motif. Correlated
      occurrences of amino acid residues at poorly conserved positions explain how TPRs
      achieve their near-neutral surface charge distributions, and why a TPR designed
      from straight consensus has an unusually high net charge. Networks of interacting
      sites revealed that TPRs fall into two unrecognized families with distinct sets
      of interactions related to the identity of position 7 (Leu or Lys/Arg).
      Statistical free energy analysis provides a more complete description of "What
      makes a TPR a TPR?" than consensus alone, and it suggests general approaches to
      extend and improve the phylogenetic design of proteins.

PMID- 15465057
TI  - The ring of the rhodopsin chromophore in a hydrophobic activation switch within
      the binding pocket.
AB  - The current view that the beta-ionone ring of the rhodopsin chromophore vacates
      its binding pocket within the protein early in the photocascade has been adopted
      in efforts to provide structural models of photoreceptor activation. This event
      casts doubt on the ability of this covalently bonded ligand to participate
      directly in later stages involving activation of the photoreceptor and it is
      difficult to translate into predictions for the activation of related G protein
      coupled receptors by diffusable ligands (e.g. neurotransmitters). The binding
      pocket fixes the formally equivalent pair of ring methyl groups (C16/C17) in
      different orientations that can be distinguished easily by (13)C NMR. Solid-state
      NMR observations on C16 and C17 are reported here that show instead that the ring
      is retained with strong selective interactions within the binding site into the
      activated state. We further show how increased steric interactions for this
      segment in the activated receptor can be explained by adjustment in the protein
      structure around the ring whilst it remains in its original location. This
      describes a plausible role for the ring in operating a hydrophobic switch from
      within the aromatic cluster of helix 6 of rhodopsin, which is coupled to
      electronic changes within the receptor through water-mediated, hydrogen-bonded
      networks between the conserved residues in G protein-coupled receptors.

PMID- 15465059
TI  - Conversion of a mechanosensitive channel protein from a membrane-embedded to a
      water-soluble form by covalent modification with amphiphiles.
AB  - Covalent modification of integral membrane proteins with amphiphiles may provide
      a general approach to the conversion of membrane proteins into water-soluble
      forms for biophysical and high-resolution structural studies. To test this
      approach, we mutated four surface residues of the pentameric Mycobacterium
      tuberculosis mechanosensitive channel of large conductance (MscL) to cysteine
      residues as anchors for amphiphile attachment. A series of modified ion channels
      with four amphiphile groups attached per channel subunit was prepared. One
      construct showed the highest water solubility to a concentration of up to 4mg/ml
      in the absence of detergent. This analog also formed native-like, alpha-helical
      homo-pentamers in the absence of detergent as judged by circular dichroism
      spectroscopy, size-exclusion chromatography and various light-scattering
      techniques. Proteins with longer, or shorter polymers attached, or proteins
      modified exclusively with polar cysteine-reactive small molecules, exhibited
      reduced to no solubility and higher-order aggregation. Electron microscopy
      revealed a homogeneous population of particles consistent with a pentameric
      channel. Solubilization of membrane proteins by covalent attachment of
      amphiphiles results in homogeneous particles that may prove useful for
      crystallization, solution NMR spectroscopy, and electron microscopy.

PMID- 15465060
TI  - The major human structural IgE epitope of the Brazil nut allergen Ber e 1: a
      chimaeric and protein microarray approach.
AB  - A protein microarray system containing different dilutions of 77 related and non
      related proteins was used to show that IgE from subjects allergic to Brazil nut
      specifically recognise the seed 2S albumin protein (Ber e 1). Further, correctly
      folded chimaeric 2S albumin proteins containing structural epitope replacement
      were constructed and directed to the secretion pathway of the methylotropic yeast
      Pichia pastoris. Through the use of a chimaeric protein microarray system
      together with sera from a panel of 18 well-characterised Brazil nut allergic
      subjects, a structural IgE epitope of Ber e 1 was mapped to a helix-loop-helix
      region. The same structural region has been previously reported as the
      immunodominant region in related food allergens by different techniques. In
      conclusion, the combination of chimaeric proteins and protein microarrays will
      greatly facilitate the screening of a large number of individuals for a
      particular structural epitope and help to further our understanding of how
      proteins are recognised by the adaptive immune system.

PMID- 15465061
TI  - Characterization of an actin-binding site within the talin FERM domain.
AB  - Talin is a large cytoskeletal protein that couples integrins to F-actin. Three
      actin-binding sites (ABS1-3) have been reported: one in the N-terminal head, and
      two in the C-terminal rod domain. Although the C-terminal ABS3 has been partially
      characterized, the presence and properties of ABS1 within the talin head are less
      well defined. We show here that the talin head binds F-actin in vitro and in vivo
      at a specific site within the actin filament. Thus, purified talin head liberated
      from gizzard talin by calpain cleavage cosediments with F-actin in a low salt
      buffer at pH 6.4 (conditions that are optimal for binding intact talin), and
      using recombinant polypeptides, we have mapped ABS1 to the FERM domain within the
      talin head. Both the F2 and F3 FERM subdomains contribute to binding, and EGFP
      tagged FERM subdomains colocalize with actin stress fibers when expressed in COS
      cells. High-resolution electron microscopy of actin filaments decorated with F2F3
      localizes binding to a site that is distinct from that recognized by members of
      the calponin-homology superfamily. Finally, we show that the FERM domain can
      couple F-actin to PIPkin, and by inference to integrins, since they bind to the
      same pocket in the F3 subdomain. This suggests that the talin FERM domain
      functions as a linker between PIPkin or integrins and F-actin at sites of cell
      matrix adhesions.

PMID- 15465062
TI  - Crystal structure of family GH-8 chitosanase with subclass II specificity from
      Bacillus sp. K17.
AB  - Crystal structures of chitosanase from Bacillus sp. K17 (ChoK) have been
      determined at 1.5 A resolution in the active form and at 2.0 A resolution in the
      inactive form. This enzyme belongs to the family GH-8, out of 93 glycoside
      hydrolase families, and exhibits the substrate specificity of subclass II
      chitosanase. The catalytic site is constructed on the scaffold of a double
      alpha(6)/alpha(6)-barrel, which is formed by six repeating helix-loop-helix
      motifs. This structure is quite different from those of the GH-46 chitosanases
      and of GH-5. Structural comparison with CelA (a cellulase belonging to the same
      family GH-8) suggests that the proton donor Glu122 is conserved, but the proton
      acceptor is the inserted Glu309 residue, and that the corresponding Asp278
      residue in CelA is inactivated in ChoK. The four acidic residues, Asp179, Glu309,
      Asp183 and Glu107, can be involved in substrate recognition through interactions
      with the amino groups of the glucosamine residues bound in the -3, -2, -1 and +1
      sites, respectively. The hydrophobic Trp235, Trp166, Phe413 and Tyr318 residues
      are highly conserved for binding of the hexose rings at the -3, -2, +1 and +2
      sites, respectively. These structural features indicate that enzymes in GH-8 can
      be further divided into three subfamilies. Different types of chitosanases are
      discussed in terms of convergent evolution from different structural ancestors.

PMID- 15465063
TI  - Type D personality, stress, and cortisol.

PMID- 15465064
TI  - Self-reported sensitivity to continuous noninvasive blood pressure monitoring via
      the radial artery.
AB  - OBJECTIVE: Many blood pressure (BP) methods common in psychosomatic research have
      salient limitations, including subject discomfort, sampling limits, and
      measurement validity concerns. This study examines the utility of the Vasotrac
      APM 205 BP monitor, which works via continuous nonocclusive compression and
      decompression of the radial artery, primarily in regard to its intrusiveness.
      METHOD: Perceptions of the device were rated by 62 university students (31
      female, 31 male) in a study involving continuous BP monitoring during an affect
      induction and film viewing. The rating scale included items assessing how
      comfortable and distracting the device was, and various sensation descriptors
      that were combined to yield compression and pain indices. RESULTS: Comfort,
      distractibility, and compression ratings clustered around the neutral midpoint of
      the 11-point scale (overall M=4.7), and pain trended toward the not at all anchor
      (M=2.2). CONCLUSIONS: Responses indicate the Vasotrac is nonintrusive during
      extended wear. Its sampling rate far exceeds that of ausculatory and
      oscillometric methods, and so it may offer further reliability and validity
      benefits for BP measurement.

PMID- 15465065
TI  - Meta-analysis of the effects of psychosocial interventions on survival time in
      cancer patients.
AB  - OBJECTIVE: To provide a quantitative summary of effects of psychosocial
      interventions on cancer survival, and to present an overview of methodological
      and reporting aspects of the studies. METHOD: Electronic searches and manual
      searches of reference lists from review articles and retrieved papers. Two coders
      independently coded study, participant, treatment, and outcome characteristics of
      the studies meeting selection criteria. RESULTS: Thirteen journal articles
      published between 1989 and 2003 reporting results from 14 controlled intervention
      studies were included. Results are based on data obtained from 2626 subjects.
      Effect sizes [hazard ratios (HR)] were heterogeneous and random effects models
      were used in the analyses. The total mean inverse-variance-weighted HR was 0.85
      (95% CI: 0.65-1.11). Randomized studies (n=8) showed no overall treatment effect
      (HR: 0.77, 95% CI: 0.56-1.06), neither did the nonrandomized studies (HR: 1.00,
      95% CI: 0.61-1.62). Interventions using individual treatment (n=3) were, however,
      found to be effective (HR: 0.55, 95% CI: 0.43-0.70) but interventions using group
      treatment (n=9) were ineffective (HR: 0.97, 95% CI: 0.73-1.27). Group treatments
      of breast cancer (n=6) were ineffective (HR: 0.95, 95% CI: 0.69-1.31).
      CONCLUSION: A definite conclusion about whether psychosocial interventions
      prolong cancer survival seems premature. Future studies should use randomization
      to avoid self-selection of patients with poor prognosis. Interventions should
      focus on a single diagnosis, take into account known risk factors, and describe
      their interventions thoroughly.

PMID- 15465067
TI  - A brief problem-solving intervention for family caregivers to individuals with
      advanced cancer.
AB  - OBJECTIVE: To evaluate a brief problem-solving intervention for family caregivers
      to individuals with advanced cancer. METHOD: Family caregivers were recruited
      through oncology clinics of a large tertiary care hospital in Canada. Those
      providing informed consent completed a baseline survey, received a brief problem
      solving intervention, received a detailed home care guide, and completed a follow
      up survey over the telephone 4 weeks after receiving the intervention. RESULTS:
      Thirty-four family caregivers completed all aspects of the study. Sixty-eight
      percent of caregivers were women, 73.5% were married to the care recipient, and
      their average age was 53.6 years. This brief intervention resulted in
      improvements in emotional tension (P<.03), caregiving confidence (P<.06), and
      positive problem-solving orientation (P<.06). CONCLUSION: These findings suggest
      that even a brief problem-solving intervention may be beneficial for family
      caregivers to individuals with advanced cancer.

PMID- 15465068
TI  - Psychosocial influences on 305 adults' survival after bone marrow
      transplantation; depression, smoking, and behavioral self-regulation.
AB  - OBJECTIVE: The role of psychological factors in adult survival after bone marrow
      transplant (BMT) has not been adequately established. BMT survival rates have
      been shown to depend largely on disease and demographic variables. With sample
      sizes no larger than 123, the majority of psychosocial studies found little
      definitive statistical evidence that mood, marital/cohabiting status, coping
      styles, or smoking affect survival. The purpose of this study was to
      comprehensively examine the relative contribution of psychological variables to
      survival after BMT in a unified model, controlling for medical and demographic
      variables. METHODS: Pre-BMT, 305 consecutive patients were psychologically
      assessed with interview and Minnesota Multiphasic Personality Inventory (MMPI).
      Transplant Evaluation Rating Scale (TERS) ratings were assigned retrospectively
      by two raters (interrater reliability r=.89). We employed a fully parametric,
      accelerated failure time regression model (Weibull), which provides richer
      extrapolation and interpretation than the semiparametric Cox proportional hazards
      regression model. RESULTS: Overall our results indicate that for a given medical
      condition, the type of BMT patient likely to survive longest was a young,
      married, educated, European-American, nonsmoker who was more defiant, better
      adjusted, and less depressed. Moreover, the longer a patient survived, the
      smaller the probability of dying in the short run. CONCLUSIONS: This study, the
      first large-scale statistical analysis using a fully parametric model (Weibull),
      provides evidence that select psychosocial variables can affect BMT survival.
      Future investigations could explore possible mediating variables, and whether
      identifying high-risk individuals pretreatment could enhance resource allocation,
      psychological intervention, and possibly even survival itself.

PMID- 15465069
TI  - Social support as a buffer in the relationship between treatment for depression
      and T-cell production of interferon gamma in patients with multiple sclerosis.
AB  - OBJECTIVE: This study examined the buffering effects of social support on the
      relationship between depression and autoaggressive immune function in multiple
      sclerosis (MS). METHODS: Fourteen participants with comorbid diagnoses of MS and
      major depressive disorder received 16 weeks of psychotherapy or antidepressant
      medications. Depression and T-cell production of interferon-gamma (IFN-gamma), a
      lynchpin in MS pathogenesis, were assessed at baseline and posttreatment. Social
      support was assessed at baseline. RESULTS: Both depression and T-cell production
      of IFN-gamma were significantly reduced over the 16 weeks of treatment. There was
      a significant interaction between change in depression, change in IFN-gamma, and
      social support (R(2)=.26, P=.03) such that social support served as a buffer.
      CONCLUSION: These results support the hypothesis that social support buffers the
      effects of change in depression on IFN-gamma production. However, these findings
      should be viewed as preliminary due to the small sample size and the absence of a
      control condition.

PMID- 15465070
TI  - Perceived importance of activities of daily living and arthritis helplessness in
      rheumatoid arthritis; a prospective investigation.
AB  - OBJECTIVE: To examine the contribution of perceived importance of activities of
      daily living (ADL) to arthritis-specific helplessness in a sample of rheumatoid
      arthritis (RA) patients over a 1-year period. METHOD: Forty-two individuals from
      an outpatient rheumatology clinic completed measures of ADL importance,
      helplessness, depression, pain, and disability; the physician's assistant
      provided objective ratings of disability. RESULTS: Time 1 importance of ADL
      predicted a significant amount of variance in Time 2 arthritis helplessness after
      statistically controlling disease and psychological covariates. Moreover,
      increased perceived ADL importance predicted decreased arthritis helplessness
      over the 1-year period. CONCLUSIONS: Results indicate that RA patients'
      experience of arthritis-specific helplessness may be minimized over time when
      performing ADL is perceived as important. Furthermore, these findings provide
      preliminary evidence for one possible antecedent to increased perceptions of
      arthritis helplessness in individuals with RA.

PMID- 15465071
TI  - The adjustment to illness in patients with generalized anxiety disorder is poorer
      than that in patients with end-stage renal disease.
AB  - Although generalized anxiety disorder (GAD) is associated with significant
      occupational disability, it has, however, received little attention with regard
      to adjustment to illness. Subjects included 102 chronic dialysis (CD) patients,
      58 kidney transplant (KT) patients, and 42 GAD patients. The evaluations included
      the Psychosocial Adjustment to Physical Illness Scale (PAIS), the Hamilton
      Anxiety Rating Scale (HAM-A) and the Hamilton Depression Rating Scale (HAM-D).
      Preanxiolytic treatment GAD patients had the most anxiety and depressive
      symptoms, followed by CD patients and KT patients. KT patients and anxiolytic
      treated GAD patients showed similar anxiety and depressive symptoms. These two
      groups were both better than CD patients. However, the adjustment to illness of
      GAD patients after treatment is still worse than the other two groups (108.0+/
      16.3(GAD), 102.0+/-14.5(CD), 81.4+/-22.2(KT); P<.001). The CD patients had a high
      rate of psychiatric morbidity and a low rate of psychiatric intervention (3%);
      however, end-stage renal disease (ESRD) patients received only one assessment
      while the GAD group received two in this study. In light of the chronicity of
      GAD, pharmacological treatment is not sufficient by itself. Clinicians should
      keep these in mind when treating either GAD or ESRD.

PMID- 15465072
TI  - Depression and lipoprotein lipids in healthy, postmenopausal women; the
      moderating effects of hormone replacement therapy.
AB  - OBJECTIVE: Naturally occurring low cholesterol levels have been related to
      increased depressive symptoms in studies conducted predominantly in men. However,
      depression is more common among women, may increase during the menopause, and may
      be impacted by hormone replacement therapy (HRT). We therefore examined the
      potential interactive relation of depressive symptoms and HRT status to
      lipoprotein lipids among postmenopausal women. METHODS: Seventy healthy,
      postmenopausal women (ages 50-70; 36% receiving HRT) completed the Center for
      Epidemiological Studies Depression Scale and provided two fasting blood samples
      for assessment of lipoprotein lipids. RESULTS: Following statistical adjustment
      for age, body mass index (BMI), HRT status, and depressive symptoms, the
      interaction of depression and HRT explained 16% variance in total cholesterol and
      17% variance in low-density lipoprotein cholesterol (Ps<.01). Greater levels of
      depressive symptoms were associated with lower cholesterol levels only among
      women who were not taking HRT. CONCLUSION: These findings suggest that HRT may
      buffer associations between naturally occurring low cholesterol levels and
      increased symptoms of depression in postmenopausal women.

PMID- 15465074
TI  - The relationship between vital exhaustion, depression and comorbid illnesses in
      patients following first myocardial infarction.
AB  - OBJECTIVE: Vital exhaustion and depression are both independent risk factors for
      cardiovascular disease, yet the relationship between these highly similar
      dimensions remains unclear. We have examined the association between depression
      and vital exhaustion and investigated the extent to which any association is the
      result of comorbid illnesses. METHODS: Three hundred and five consecutive
      patients were examined on average 3.6 days following hospital admission with
      first myocardial infarction (MI). The Maastricht Questionnaire (MQ; vital
      exhaustion) was administered together with the Hospital Anxiety and Depression
      Scale (HADS), and details of comorbid physical illness were recorded. The factor
      structure of the MQ was explored using factor analysis. RESULTS: Depression and
      vital exhaustion were highly correlated (r=.61, P<.01). This correlation did not
      diminish on controlling for age, sex, and comorbidity (r=.59, P<.01). Factor
      analysis of MQ score gave a four-factor solution: fatigue (18.2% of variance),
      depression (17.9%), lack of concentration (9.5%), and sleep difficulties (8.1%).
      The fatigue dimension of the MQ remained highly associated with HADS depression
      score (r=.50, P<.01), controlling for age, sex, and comorbidity. CONCLUSIONS:
      Depression and fatigue are highly correlated and their association is not
      attributable to comorbid physical illnesses or the tendency of the MQ to measure
      depression. Future studies should investigate fatigue instead of vital exhaustion
      as a potential risk factor for poor cardiac prognosis independent of the
      influence of depression.

PMID- 15465075
TI  - Mild acute inflammatory stimulation induces transient negative mood.
AB  - OBJECTIVE: This study aims to assess the mood changes induced by mild acute
      inflammatory stimulation (typhoid vaccination). METHODS: Using a double blind
      study design, 26 healthy volunteers underwent baseline assessments of mood,
      financial strain and work stress and were randomised to injection of Salmonella
      typhi vaccine or placebo injection. Mood, symptoms and body temperature was
      assessed by a modified version of the Profile of Mood States at 1, 2, 3, 4, 6 and
      8 h post injection. RESULTS: Typhoid vaccination induces no increases in physical
      symptoms or temperature. Mood improved over the day in the placebo but not in the
      vaccine condition. Negative changes in mood following injection were correlated
      with chronic stress (financial strain) in the vaccination condition (r=-.65,
      P<.025). CONCLUSION: A mild acute inflammatory stimulus induces transient
      negative mood, and responses were modulated by chronic stress. Implications for
      depressed mood in physical illness are discussed.

PMID- 15465076
TI  - The impact of psychological and clinical factors on quality of life in
      individuals with atopic dermatitis.
AB  - OBJECTIVE: The aim of the study was to assess the influence of general and
      dermatitis-specific psychological and clinical factors on quality of life in
      adults with atopic dermatitis (AD). METHOD: A total of 125 adults recruited
      through the National Eczema Society of U.K. (NES) completed a number of
      psychological and dermatological questionnaires, including the Dermatology Life
      Quality Index (DLQI), the Stigmatisation and Eczema Questionnaire (SEQ), the
      Hospital Anxiety and Depression Scale (HADS), the Fear of Negative Evaluation
      Scale (FNE) and the Rosenberg Self-Esteem Scale (RSE). RESULTS: Pearson's
      correlational analyses suggested that perceptions of stigma were significantly
      associated with psychological factors as well as quality of life (Ps<.01). An
      association was also found between perceived stigma and disease severity (-.28,
      P<.01). Almost 46% of participants were identified as having probable mood
      disorder. Regression analysis indicated that perceptions of stigma and depression
      accounted for 44.5% of the variance in quality of life in this sample
      [F(3,121)=34.18, P<.001], when disease severity was controlled for. CONCLUSION:
      Psychological factors and disease severity were strong predictors of quality of
      life in adults with AD. AD-related perceptions of stigma were of particular
      importance in predicting AD-related quality of life over and above more general
      psychological factors, such as depression. These findings have important
      implications for the psychological and clinical management of AD.

PMID- 15465077
TI  - Psychometric study of quality of life instruments used during hospitalization for
      stem cell transplantation.
AB  - OBJECTIVE: To test the psychometric properties of four patient-rated quality of
      life (QoL) instruments devised by the authors: three single-item instruments
      measuring (1) overall physical status, (2) overall emotional status, and (3)
      energy level, and one eight-item instrument measuring systemic symptoms. METHOD:
      In a prospective inpatient study conducted from July 1994 to August 1997, 220
      patients aged 16-65 years received hematopoietic stem cell transplantation (SCT)
      for hematologic cancer at a single institution. Patients were assessed at
      hospital admission and then on a weekly basis during hospitalization until
      discharge or death. RESULTS: Internal consistency reliability and test-retest
      reliability of the tested scales were adequate. Convergent, divergent, criterion,
      and predictive validities as well as responsiveness to change of our scales were
      demonstrated by significant associations with their tested constructs.
      CONCLUSION: Our data indicate that the four QoL instruments are reliable and
      valid for use during hospitalization for SCT.

PMID- 15465078
TI  - Optimizing an individual's treatment in acute stroke: is a magnetic resonance map
      leading us towards the holy grail?

PMID- 15465079
TI  - Influence of pretreatment MRI parameters on clinical outcome, recanalization and
      infarct size in 49 stroke patients treated by intravenous tissue plasminogen
      activator.
AB  - We hypothesized that pretreatment magnetic resonance imaging (MRI) parameters
      might predict clinical outcome, recanalization and final infarct size in acute
      ischemic stroke patients treated by intravenous recombinant tissue plasminogen
      activator (rt-PA). MRI was performed prior to thrombolysis and at day 1 with the
      following sequences: magnetic resonance angiography (MRA), T2*-gradient echo (GE)
      imaging, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI).
      Final infarct size was assessed at day 60 by T2-weighted imaging (T2-WI). The
      National Institutes of Health Stroke Scale (NIHSS) score was assessed prior to rt
      PA therapy and the modified Rankin Scale (m-RS) score was assessed at day 60. A
      poor outcome was defined as a day 60 m-RS score >2. Univariate and multivariate
      logistic regression analyses were used to identify the predictors of clinical
      outcome, recanalization and infarct size. Forty-nine patients fulfilled the
      inclusion criteria. Baseline NIHSS score was the best independent indicator of
      clinical outcome (p=0.002). A worse clinical outcome was observed in patients
      with tandem internal carotid artery (ICA)+middle cerebral artery (MCA) occlusion
      versus other sites of arterial occlusion (p=0.009), and in patients with larger
      pretreatment PWI (p=0.001) and DWI (p=0.01) lesion volumes. Two factors predict a
      low rate of recanalization: a proximal site of arterial occlusion (p=0.02) and a
      delayed time to peak (TTP) on pretreatment PWI (p=0.05). The final infarct size
      was correlated with pretreatment DWI lesion volume (p=0.025). Recanalization was
      associated with a lower final infarct size (p=0.003). In conclusion, a severe
      baseline NIHSS score, a critical level of pretreatment DWI/PWI parameters and a
      proximal site of occlusion are predictive of a worse outcome after IV rt-PA for
      acute ischemic stroke.

PMID- 15465080
TI  - Impact of aerobic training on immune-endocrine parameters, neurotrophic factors,
      quality of life and coordinative function in multiple sclerosis.
AB  - In recent years it has become clear that multiple sclerosis (MS) patients benefit
      from physical exercise as performed in aerobic training but little is known about
      the effect on functional domains and physiological factors mediating these
      effects. We studied immunological, endocrine and neurotrophic factors as well as
      coordinative function and quality of life during an 8-week aerobic bicycle
      training in a waitlist control design. In the immune-endocrine study (1) 28
      patients were included, the coordinative extension study (2) included 39
      patients. Training was performed at 60% VO(2)max after determining individual
      exertion levels through step-by-step ergometry. Metabolic (lactate), endocrine
      (cortisol, adrendocortico-releasing hormone, epinephrine, norepinephrine), immune
      (IL-6, soluble IL-6 receptor), and neurotrophic (brain-derived neurotrophic
      factor (BDNF), nerve growth factor (NGF)) parameters were compared from a
      prestudy and a poststudy endurance test at 60% VO(2)max for 30 min. In study (1),
      lowered lactate levels despite higher workload levels indicated a training
      effect. Disease-specific quality of life (as measured by the Hamburg Quality of
      Life Questionnaire for Multiple Sclerosis, HAQUAMS) significantly increased in
      the training group. No significant training effects were seen for endocrine and
      immune parameters or neurotrophins. In study (2), two out of three coordinative
      parameters of the lower extremities were significantly improved. In summary, low
      level aerobic training in MS improves not only quality of life but also
      coordinative function and physical fitness.

PMID- 15465081
TI  - Familial amyotrophic lateral sclerosis with His46Arg mutation in Cu/Zn superoxide
      dismutase presenting characteristic clinical features and Lewy body-like hyaline
      inclusions.
AB  - We evaluated the characteristic clinical features of one family of familial
      amyotrophic sclerosis (FALS) with a His46Arg mutation in the enzyme Cu/Zn
      superoxide dismutase (SOD1). Codon 46 encodes the binding site for copper and the
      His46Arg mutation may result in decreased copper binding and copper toxicity. The
      disease duration of this family was 17.8+/-13.2 years (mean+/-S.D.) with the age
      at onset being 42.9+/-4.7 years old (mean+/-S.D.). The initial sign was distal
      weakness of the unilateral lower limb, extending to the other lower limb. An
      autopsy was performed on a 62-year-old female member of the family who had the
      mutation. Her disease duration was 23 years, and she died of tonsillar herniation
      caused by metastasis of colon cancer in the cerebellum. Neuropathological
      findings showed marked loss of large anterior horn cells and very mild
      degeneration of corticospinal tracts as well as posterior columns. The number of
      nuclei of Clark's column was reduced. Lewy body-like hyaline inclusion bodies
      (LBHIs) were frequently seen in the remaining anterior horn cells. Astrocytic
      hyaline inclusions (Ast-HIs) were also seen. This is the first autopsy report of
      FALS with a His46Arg mutation presenting neuronal LBHIs and Ast-HIs. The
      formation of LBHIs and Ast-HIs may be dependent on the phenotype of the
      preferential lower motor neuron involvement in FALS with a SOD mutation and long
      disease duration.

PMID- 15465082
TI  - High frequency of allergic conjunctivitis in myasthenia gravis without thymoma.
AB  - OBJECTIVES: To investigate the frequency of allergic disorders in myasthenia
      gravis (MG) patients and characterize the features of MG associated with allergic
      disorders. METHODS: Frequencies of past and present common allergic disorders in
      160 MG patients who visited the Department of Neurology, Kyushu University
      Hospital from April 2000 to July 2003 and in 81 neurological normal controls were
      studied. RESULTS: Among various allergic disorders, the frequency of allergic
      conjunctivitis (AC) was significantly higher in MG patients (39/160, 24.4%,
      p(corr)=0.0112), especially with MG without thymoma (36/123, 29.3%,
      p(corr)=0.0016), in comparison to the controls (6/81, 7.4%). MG patients with AC
      showed a significantly higher rate of seronegative MG (43.6% vs. 17.4%, p=0.008)
      and a higher tendency of ocular MG (43.6% vs. 28.1%, p=0.071). Moreover, MG with
      AC had significantly lower anti-acetylcholine receptor antibody titers (median
      6.8 nmol/l vs. median 23.6 nmol/l, p=0.0359) as well as a lower rate of
      coexisting thymoma (7.7% vs. 17.4%, p=0.016). The incidence of myasthenic crisis
      was also lower in MG with AC than without AC, yet the difference was not
      significant (7.7% vs. 15.7%). CONCLUSION: There was a significant association of
      AC with MG especially for ocular or seronegative MG in cases without thymoma.

PMID- 15465083
TI  - Quantitative evaluation of age-related white matter microstructural changes on
      MRI by multifractal analysis.
AB  - Multifractal analysis has been applied to evaluate biological tissues, which are
      composed of complex structures. We carried out multifractal analyses in a group
      of healthy young and elderly subjects to examine age-related white matter
      microstructural changes on T2-weighted MR images without any visible abnormal
      intensity, and to correlate such changes with age-related cognitive decline.
      Comparison between the two age groups showed that Deltaalpha (established as the
      most suitable index of heterogeneity in our previous report) in the frontal
      region was significantly higher in the elderly group, but no significant group
      difference was found in Deltaalpha in the parieto-occipital region. The Trail
      Making Test score (a measure of executive dysfunction) was significantly higher
      in the elderly group. In the elderly group, the Trail-Making Test score was
      positively correlated with Deltaalpha in the frontal region, but not in the
      parieto-occipital region. These results suggest that microstructural changes in
      the white matter preferentially occur in the frontal region with normal aging,
      and these changes are associated with executive cognitive decline reflective of
      frontal-subcortical dysfunction.

PMID- 15465084
TI  - Nicotinic acetylcholine receptor immunohistochemistry in Alzheimer's disease and
      dementia with Lewy bodies: differential neuronal and astroglial pathology.
AB  - Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are common forms of
      dementia in the elderly. The neuropathology of AD and DLB is related to
      cholinergic dysfunctions, and both alpha4 and alpha7 nicotinic acetylcholine
      receptor (nAChR) subunits are decreased in several brain areas in both diseases.
      In this immunohistochemical study, we compared neuronal and astroglial alpha4 and
      alpha7 subunits in AD, DLB and age-matched controls in the hippocampal formation.
      The numbers of alpha4 reactive neurons were decreased in layer 3 of the
      entorhinal cortex of AD and DLB, whereas those of alpha7 reactive neurons were
      decreased in layer 2 of the subiculum of AD and DLB and in layer 3 of the
      entorhinal cortex of DLB. In contrast, the intensity of alpha7 reactive neuropil
      was significantly higher in AD than in controls or DLB in a number of areas of
      the hippocampus (CA3/4 and stratum granulosum), subiculum and entorhinal cortex.
      An increase in alpha7 immunoreactivity in AD was also associated with astrocytes.
      The number of astrocytes double-labelled with alpha7 and glial fibrillary acidic
      protein (GFAP) antibodies was increased in most areas of the hippocampus and
      entorhinal cortex in AD compared with controls and DLB. Increased astrocyte
      alpha7 nAChRs in AD may be associated with inflammatory mechanisms related to
      degenerative processes specific to this disease.

PMID- 15465085
TI  - Isolated cranial neuropathy associated with anti-glycolipid antibodies.
AB  - We describe seven patients with isolated cranial neuropathy in whom serum anti
      glycolipid antibodies were detected. Trigeminal sensory neuropathy was found in
      four patients, who had exhibited symptoms for 2 months to 4 years. The other
      three patients showed facial nerve palsy with or without ophthalmoparesis.
      Temporal profile analysis of anti-glycolipid antibodies revealed that titers of
      anti-glycolipid IgM antibodies against GM2 and LM1 gradually decreased in
      patients having chronic trigeminal sensory neuropathy. In patients with acute
      trigeminal sensory neuropathy, elevation of anti-LM1 antibody titers continued
      over 12 months although anti-GalNAc-GD1a antibody disappeared. On the other hand,
      titers of anti-glycolipid antibodies rapidly decreased in patients with acute
      facial nerve palsy with or without ophthalmoparesis. We conclude that anti
      glycolipid antibodies may play an important role in the development of isolated
      cranial neuropathy in some patients.

PMID- 15465086
TI  - Microarray analysis in Tourette syndrome postmortem putamen.
AB  - Gene expression patterns in the postmortem putamen of patients with Tourette
      syndrome (TS) were investigated using cDNA microarrays. A cDNA neuroarray
      comprising 1537 genes known to be related to neurological or neuropsychiatric
      disorders was used to compare patient samples (n=3) with those from control
      subjects (n=4). Z test and Z ratio were used to analyze results; seven genes were
      found to be upregulated according to our definition (P<0.1, two-tailed, for Z
      test; P<0.05 for Z ratio) and three were found to be downregulated. Validation
      experiments were performed using reverse transcription polymerase chain reaction
      (RT-PCR) and semiquantitative Western blot analyses. RT-PCR showed concordance
      with microarray in seven of nine selected genes. In contrast, Western blot
      analyses performed with five proteins showed that only two of five had similar
      trends between protein content and level of gene expression. The authors note the
      inherent difficulty in applying microarray technology to complex neurological
      disorders such as the TS and conclude that further investigations are required to
      understand how altered expression of these genes is related to the
      pathophysiology of the disorder.

PMID- 15465087
TI  - Crossed cerebellar hypoperfusion in hyperacute ischemic stroke.
AB  - OBJECTIVE: In chronic stage of cerebral hemispheric infarction, contralateral
      cerebellar blood flow and metabolism are depressed, which is known as crossed
      cerebellar diaschisis (CCD). The present study was performed to elucidate (1)
      whether the diaschisis occurs in hyperacute stage of ischemic stroke when
      computed tomography (CT) scans is not able to identify infarction, and (2) which
      site of lesion in the cerebrum is responsible for the depression in contralateral
      cerebellar blood flow. METHODS: Single photon emission computed tomography was
      performed in 21 patients with middle cerebral artery (MCA) embolic infarction
      within 6 h of the onset (3.2+/-1.1 h, mean+/-S.D.). Regions of interest (ROIs)
      were symmetrically located in the cerebral hemispheres including cerebral cortex
      and subcortex, and in the cerebellar hemispheres. RESULTS: The side-to-side ratio
      of cerebellar blood flow ipsilateral to that contralateral to cerebral infarct
      was significantly increased compared with that in normal control (P<0.001),
      indicating that contralateral cerebellar blood flow was significantly depressed.
      In hyperacute stage, the ratio of cerebellar blood flow appeared to be associated
      with the ratio of cerebral blood flow in whole hemispheres (r=0.44, P<0.05), in
      anterior frontal lobe (r=0.44, P<0.05) and in anterior temporal lobe (r=0.58,
      P<0.01), but not in infarct areas (r=0.26, P=0.3). Stepwise regression analysis
      revealed that the ratios in cerebellar hemispheres were associated with those in
      anterior temporal lobe (multiple regression analysis, r=0.58, P<0.01).
      CONCLUSIONS: Crossed cerebellar diaschisis occurs at hyperacute stage of stroke
      of the MCA infarction. It may be related to the hypoperfusion in the anterior
      frontal and anterior temporal lobes of the cerebrum where regional blood flow is
      decreased by ischemic infarction per se or by ipsilateral hemispheric depression
      from infarct area (diaschisis mechanism).

PMID- 15465088
TI  - Attack-related severity: a key factor in understanding the spectrum of idiopathic
      inflammatory demyelinating disorders.
AB  - Understanding the spectrum of idiopathic inflammatory demyelinating disorders
      (IIDD) is a fundamental issue for the diagnosis and treatment of these disorders
      as well as for the approach to their pathogenesis. The spectrum of IIDD is
      usually classified according to clinical course and lesion distribution. We
      compared the demographic features, clinical characteristics, laboratory findings,
      and genetic backgrounds between 193 Japanese patients with and without clinically
      or radiographically fulminant attacks who all satisfied the diagnostic criteria
      for multiple sclerosis (MS). "Fulminant attacks" in the current study represent
      attack-related clinically or radiologically severe relapses but do not
      necessarily mean severe disability. Patients with fulminant attacks were
      clinically and immunogenetically distinct from those free of such attacks, and
      the previously described characteristics of the opticospinal form of MS (OSMS) or
      neuromyelitis optica (NMO) were mostly shared by patients with fulminant attacks.
      HLA profiles were similar among patients with fulminant attacks irrespective of
      the lesion distributions. The GG homozygous and G alleles of the CTLA4 gene A/G
      coding SNP at position 49 in exon 1 were significantly more common in patients
      with fulminant attacks than in those without. Attack-related severity may be an
      important factor if validated by prospective studies defining criteria and
      establishing relationships to disease course and treatment regimens.

PMID- 15465090
TI  - Variation in ischemic stroke frequency in Japan by season and by other variables.
AB  - BACKGROUND AND PURPOSE: It is unclear whether acute ischemic stroke exhibits a
      seasonal pattern in Japan. The aim of the present study was to elucidate seasonal
      differences in acute ischemic stroke. METHODS: Our study enrolled 12,660 patients
      with ischemic stroke (7943 men, 4717 women; mean age, 70.1 years, S.D. 11.5;
      median 70; range 18-107). We divided the year into four parts: spring (March
      May); summer (June-August); fall (September-November); and winter (December
      February). Time of stroke onset was divided into three subgroups: daytime (08:00
      16:00), evening (16:00-24:00), and night (24:00-08:00). We examined the
      association between clinical characteristics, season, and time of stroke onset.
      RESULTS: Stroke occurred least frequently in spring (22.9%), followed by winter
      (25.3%), fall (25.8%), and summer (26.0%) (P<0.001). No differences in age,
      National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale
      (m-RS) score, history of stroke/transient ischemic attack (TIA), or risk factors
      for stroke were observed among the four seasons. Stroke in men (63.8% vs. 62.4%;
      P<0.01), lacunar stroke (LS) (41.2% vs. 39.4%, P<0.01), atherothrombotic stroke
      (ATS) (34.0% vs. 32.3%; P<0.01), and nighttime stroke (26.5% vs. 24.8%; P<0.05)
      were observed more frequently in summer compared to other seasons. This contrasts
      with the findings for stroke in women (39.0% vs. 36.7%; P<0.05), cardioembolic
      stroke (CES) (23.4% vs. 20.6%; P<0.05), and daytime stroke (47.4% vs. 45.0%;
      P<0.05), which were more frequent in winter. CONCLUSIONS: Acute ischemic stroke
      displays seasonal characteristics according to gender, stroke subtype, and time
      of stroke onset. These results may have important clinical implications in
      ischemic stroke prevention.

PMID- 15465089
TI  - CCR2-64I polymorphism and CCR5Delta32 deletion in patients with Alzheimer's
      disease.
AB  - Monocyte chemoattractant protein-1 (MCP-1) and RANTES, as well as their related
      receptors, have been shown to be involved in Alzheimer's disease (AD)
      pathogenesis. Genes for their related receptors, CCR2 and CCR5, respectively, are
      characterized by the presence of two polymorphisms: a conservative change of a
      valine with an isoleucine at codon 64 of CCR2 (CCR2-64I) and a 32-bp deletion in
      the coding region of CCR5 (CCR5Delta32), which leads to the expression of a
      nonfunctional receptor. The distribution of the CCR2-64I and CCR5Delta32
      polymorphisms was determined in 290 AD patients and in 222 controls. A decreased
      frequency and an absence of homozygous for the polymorphism CCR2-64I were found,
      thus suggesting a protective effect of the mutated allele on the occurrence of
      AD. However, these findings must be cautiously interpreted as the overall
      significance was found without adjustment for multiple comparisons and is coming
      from the complete absence of the genotype 64I/64I in AD patients. Conversely, no
      different distribution of the CCR5Delta32 deletion in the two populations was
      shown. Stratifying by the presence of ApoE varepsilon4 allele, gender or age at
      onset, no differences in either allele frequencies were observed.

PMID- 15465091
TI  - Neurophysiological and immunohistochemical studies on Guillain-Barre syndrome
      with IgG anti-GalNAc-GD1a antibodies-effects on neuromuscular transmission.
AB  - We investigated the epitopes and functional role of IgG anti-GalNAc-GD1a
      antibodies appearing in serum from a patient with Guillain-Barre syndrome (GBS)
      and IgG anti-GalNAc-GD1a antibody that was produced by immunization of a rabbit
      with GalNAc-GD1a. Both sera blocked neuromuscular transmission in muscle-spinal
      cord co-culture cells. The acetylcholine-induced potential did not reduce by
      adding sera, suggesting that the blockade is presynaptic. The effect was
      complement-independent and purified IgG from serum of the patient or the rabbit
      had the same effects. The epitope with both anti-GalNAc-GD1a antibodies was
      observed in the soma of large neurons in the anterior horns of the adult rat
      spinal cord and their motor axons of rat ventral roots. Both anti-GalNAc GD1a
      antibodies reacted strongly with the motor nerve terminals in rats. The anti
      GalNAc-GD1a antibodies may block neuromuscular transmission by attacking on
      presynaptic motor axon, probably affecting the ion channels in the presynaptic
      motor axon.

PMID- 15465092
TI  - Childhood neurological presentation of a novel mitochondrial tRNA(Val) gene
      mutation.
AB  - We describe a young girl with a novel 1659T>C mutation in the tRNA(Val) gene of
      mitochondrial DNA (mtDNA) who presented with learning difficulties, hemiplegia,
      and a movement disorder, together with a raised cerebrospinal fluid (CSF)
      lactate. The mutation, which was present at high levels of heteroplasmy in
      patient tissues, interrupts a conserved Watson-Crick basepair in the TPsiC stem
      and has not previously been described in controls. This report further confirms
      the frequent association of mitochondrial tRNA mutation with neurological
      presentations, even in paediatric cases.

PMID- 15465093
TI  - Feasibility of combining multi-channel functional neuromuscular stimulation with
      weight-supported treadmill training.
AB  - More than 3 million stroke survivors live with residual disabilities and mobility
      deficits even after rehabilitation. Therefore, it is important to develop new,
      more effective, gait training methods. The purpose of this study was twofold: (1)
      testing the feasibility of combining multi-channel functional neuromuscular
      stimulation (FNS) using intramuscular (IM) electrodes and body weight supported
      treadmill training (BWSTT) for gait training; and (2) documenting the potential
      gait practice advantages afforded by combining FNS-IM and BWSTT. Eight subjects
      with gait deficits in the chronic phase (>12 months) were enrolled. Intramuscular
      electrodes were placed in the paretic hip abductors, knee flexors and extensors,
      and ankle dorsiflexors, plantarflexors, and evertors. Subjects were treated with
      exercise and gait training using the combined technologies 1 1/2 h/week, four
      times/week, for 12 weeks. Feasibility was tested according to performance of the
      technologies, clinician skill factors, and subject satisfaction. Impairment,
      function, and quality of life were measured. Provision of practice for eight gait
      characteristics was catalogued. We found the following results for the combined
      technologies: (1) the combined technologies were safe and feasible; (2)
      clinicians required five training sessions to reach proficiency; (3) subjects
      were satisfied; (4) there were significant gains in impairment and functional
      measures; (5) a greater number of gait practice characteristics were provided
      with the combined technologies than with either alone.

PMID- 15465094
TI  - Survival-determining factors in patients with neurologic impairments who received
      home health care in Japan.
AB  - BACKGROUND: The Japanese have become the longest-lived nation population in the
      world, and numbers of elderly who require medical and nursing care are
      increasing. The capacity of nursing homes and nursing institutions is sharply
      limited in Japan; further, as a group, elderly Japanese patients prefer home care
      to institutional care. For these reasons, the home health care system in Japan
      has been increasingly important. OBJECTIVE: We sought to identify factors
      determining long-term survival in Japanese patients receiving home health care
      for neurologic disorders. PATIENTS AND METHODS: We retrospectively evaluated 180
      patients with neurologic disease, who received home health care conducted by our
      hospital between 1992 and 2001. Factors considered were age; gender; illnesses;
      prognosis; follow-up period; activities of daily living (ADL); behavioral,
      cognitive, and communicative functions; swallowing function; feeding method;
      serum nutritional values (total protein, albumin, and total cholesterol);
      hemoglobin concentration; and social care services provided at home. RESULTS:
      Variables affecting long-term survival in 180 patients with neurologic disease
      were age (P<0.0002) and severity of dysphagia (P<0.04) by Cox's proportional
      hazard test. CONCLUSION: Maintenance of swallowing function and adequate
      nutrition through a variety of feeding methods that can be provided by a home
      health care program are important for long-term survival of patients with stroke
      and also that of patients with other neurologic diseases.

PMID- 15465095
TI  - Asymptomatic hereditary Alexander's disease caused by a novel mutation in GFAP.
AB  - We report on a family with dominantly inherited asymptomatic Alexander's disease
      due to a novel Glial fibrillary acidic protein (GFAP) mutation. The proband, a 16
      month-old boy, presented with megalocephaly and brain magnetic resonance imaging
      (MRI) showing the typical findings of Alexander's disease. Molecular analysis
      showed that he was a heterozygote of the L331P mutation of GFAP. His mother and
      sister, without megalocephaly or other neurological abnormalities, were also
      heterozygotes of the mutation and their brain magnetic resonance imaging showed
      mild changes in the caudates and deep frontal white matters. These results
      suggest the existence of a forme fruste of Alexander's disease. The L331P
      mutation may be associated with the mild phenotype of Alexander's disease. To
      elucidate the genotype-phenotype correlation in Alexander's disease, molecular
      diagnosis and MRI examination are required for many patients and their families.

PMID- 15465096
TI  - Pantothenate kinase-associated neurodegeneration initially presenting as postural
      tremor alone in a Japanese family with homozygous N245S substitutions in the
      pantothenate kinase gene.
AB  - We describe a 24-year-old Japanese woman with pantothenate kinase-associated
      neurodegeneration (PKAN) whose only early symptom was postural tremor in the
      right hand at around 18 years of age, leading to a diagnosis of essential tremor
      at age 21. Although she was treated with arotinolol hydrochloride and clonazepam,
      she gradually progressed to extrapyramidal and pyramidal signs several years
      later. T2-weighted magnetic resonance images (MRI) showed bilaterally marked
      hypointensity with a central region of hyperintensity in the globus pallidus, or
      the so-called "eye-of-the-tiger" sign. Six years have passed since the initial
      appearance of postural tremor, whereas she has not shown choreoathetosis,
      retinitis pigmentosa, optic atrophy, or seizure. Direct sequencing of the
      patient's genomic DNA revealed homozygous base substitutions in the pantothenate
      kinase gene (PANK2): the A764-->G substitution (N245S) due to consanguinity of
      her parents. Although the heterozygous form of this mutation has already been
      reported among several families, this is the first report of the homozygous
      mutation in a patient with atypical-type PKAN. This detailed description of the
      clinical features of a Japanese patient with PKAN arising from homozygous N245S
      mutations in PANK2 would be useful for elucidating the pathogenesis of PKAN.

PMID- 15465097
TI  - Prediction of psychiatric response to donepezil in patients with mild to moderate
      Alzheimer's disease.
AB  - Donepezil is a selective acetylcholinesterase inhibitor approved for the
      symptomatic treatment of mild to moderate Alzheimer's disease (AD). Since
      behavioral symptoms severely affect quality of life for AD patients and their
      caregivers, predicting behavioral responses to donepezil will be useful in
      managing patients with AD. In this study, we analyzed 70 consecutive cases with
      mild to moderate AD. Caregivers were interviewed with the Neuropsychiatric
      Inventory for behavioral assessment and 4-point improvement at week 12 was
      accepted as a treatment response. Twenty-one (30.0%) patients showed a behavioral
      response, while 42 (60.0%) showed no behavioral change and 7 (10.0%) worsened.
      Dysphoria, anxiety and apathy significantly improved after treatment among the
      responder group. The baseline profile including age, sex, Mini-Mental State
      Examination (MMSE), the Alzheimer's Disease Assessment Scale (ADAS-cog) and the
      Geriatric Depression Scale did not differ significantly among the three groups.
      Statistical Parametric Mapping analysis of single photon emission computed
      tomography (SPECT) images at baseline showed that cerebral blood flow in the
      premotor and parietotemporal cortices was significantly higher in the responder
      group than in the worse group. The present study suggested usefulness of SPECT
      imaging in the prediction of behavioral response to donepezil among AD patients
      even with similar psychiatric symptoms and cognitive functions.

PMID- 15465098
TI  - An autopsied case of Sjogren's syndrome with massive necrotic and demyelinating
      lesions of the cerebellar white matter.
AB  - A 69-year-old woman developed subacute cerebellar ataxia and tremors in all four
      limbs in April 1996. Laboratory examination showed elevated antibodies against Ro
      and La. Head magnetic resonance imaging showed T(2) high-intensity lesions in the
      cerebellar white matter bilaterally and later in the pons. In April 2000, she
      died of multiple organ failure with incidental colon cancer. The autopsy showed
      atrophic parotid glands with an accumulation of lymphocytes around the ducts,
      confirming the diagnosis of Sjogren's syndrome histopathologically. The
      neuropathological examination revealed severe necrotic lesions in the cerebellar
      white matter bilaterally with several foci of perivenous demyelination in the
      periphery of the lesions and similar demyelinated areas in the pons.
      Immunohistochemistry with anti-JC virus antibody demonstrated no positive
      inclusions. A single focus of granulomatous arteritis was observed in one
      subarachnoid artery. The combination of Sjogren's syndrome, granulomatous
      angitis, and foci of perivenous demyelination suggests that an autoimmune
      mechanism played an important role in causing the necrotic lesions in the
      cerebellar white matter in this case.

PMID- 15465099
TI  - Pica-associated cerebral edema in an adult.
AB  - Acute cerebral edema due to lead intoxication is an unusual presentation in an
      adult. Here we describe an adult with pica presenting with severe encephalopathy
      due to extremely high lead levels (>200 microg/dl) with marked cerebral edema and
      mild hyperammonemia. Rapid initiation of chelation therapy led to a reduction in
      serum lead and ammonia levels and a resolution of the cerebral edema and
      encephalopathy, suggesting a close relationship between lead toxicity and hepatic
      dysfunction.

PMID- 15465100
TI  - Unusual neuro-ophthalmologic findings in a patient with anti-Yo-associated
      cerebellar degeneration.
AB  - We report a woman with anti-Yo-associated cerebellar degeneration, severe eye
      movement abnormalities, and no evidence of malignancy after 3 years of extensive
      evaluation. The prominent neuro-ophthalmologic findings suggest brainstem
      involvement, which may be a novel manifestation of anti-Yo associated
      paraneoplastic syndrome.

PMID- 15465102
TI  - Cognitive dysfunction in cholesterol embolic disease.
AB  - A patient who developed neurological and renal complications following coronary
      angiogram and coronary artery bypass grafting is reported. Neurological
      involvement was in the form of fluctuating sensorium and a subcortical pattern of
      dementia. Renal failure was seen in the form of raised urea and creatinine
      levels. Renal biopsy revealed the cause of the renal failure to be due to
      cholesterol embolic disease. While the sensorium often improved following renal
      replacement therapy (dialysis), the dementia was poorly responsive to therapy.
      The patient succumbed due to progressive renal failure. Awareness of the protean
      manifestations and a high index of suspicion are essential for appropriate
      diagnosis in order to enable the clinician to accurately prognosticate in this
      often fatal disease.

PMID- 15465101
TI  - Epilepsia partialis continua as an isolated manifestation of motor cortical
      dysplasia.
AB  - Cortical dysplasia has been increasingly recognized as a cause of epilepsy. We
      describe herein a 31-year-old female patient with epilepsia partialis continua
      (EPC) in the right extremities, which had lasted for 15 years without generalized
      seizures and other neurological deteriorations. MRI showed a focal thickening
      around the left motor area, indicative of cortical dysplasia, with adjacent
      subcortical abnormal T2 high intensity, suggestive of dysmyelination.
      Transcranial magnetic stimulation revealed low motor thresholds and markedly
      prolonged latencies of motor-evoked potentials (MEP) of the affected side,
      consistent with hyperexcitability of the cortical motoneurons accompanied by
      dysmyelination. This case demonstrates that motor cortex dysplasia can result in
      a mild and non-progressive form of epilepsia partialis continua, associated with
      the characteristic MRI and MEP abnormalities.

PMID- 15465103
TI  - Syntheses of acetylated steroid glycosides and selective cleavage of O-acetyl
      groups in sugar moiety.
AB  - Acetylated 3beta-O-beta-glycosyl steroid derivatives were synthesized by the
      reaction of a new polyhydroxysteroid 3beta,5alpha,6beta-trihydroxypregn-16-en-20
      one (2) with the peracetylated 1-bromo derivatives of d-glucose and d-galactose,
      respectively. Subsequent protection by excess acetic anhydride in pyridine
      selectively gave the 6beta-O-acetylated steroid glycosides. Deprotection of the
      acetylated steroid glycosides separately with moderate catalysis dibutyltin oxide
      in methanol selectively removed all acetyl groups of sugar moiety, whereas the
      acetyl group of the steroid part was retained. The structures of the steroid
      glycosides were confirmed by mass spectrometry, NMR and IR. The complete protocol
      was shown to be non-destructive at all stages to the sugar moieties and the
      steroid nucleus. These regioselective reactions open a route to the synthesis of
      a series of closely related isomers of 2 and other widespread polyhydroxysteroids
      and steroid glycosides in marine organisms and some terrestrial species.

PMID- 15465104
TI  - Synthesis of 3-methyl-3-hydroxy-6-oxo-androstane derivatives.
AB  - 3alpha,17beta-Dihydroxy-3beta-methyl-5alpha-androstan-6-one (1) and 3beta,17beta
      dihydroxy-3alpha-methyl-5alpha-androstan-6-one (13) were prepared by the reaction
      of methylmagnesium bromide with the 3-ketosteroids. Structures and configurations
      in position 3 were determined by NMR spectra. Substitution in the position 6
      influences the ratio of the products.

PMID- 15465105
TI  - Synthesis of phytoestrogenic isoflavonoid disulfates.
AB  - Di-O-sulfates of six phytoestrogenic isoflavonoids, daidzein (1), genistein (2),
      glycitein (3), and the reduced metabolites dihydrodaidzein (4), dihydrogenistein
      (5) and equol (6) were synthesized. These compounds are known or potential
      inhibitors of steroid sulfatase enzymes. The new compounds were characterized by
      NMR and mass spectrometry.

PMID- 15465106
TI  - Synthesis of [26,27-2H6]brassinosteroids from 23,24-bisnorcholenic acid methyl
      ester.
AB  - A number of hexadeuterated brassinosteroids (BS) containing a hydroxy group at C
      22 or a 22R,23R-diol function were prepared starting from 23,24-bisnorcholenic
      acid methyl ester for biosynthetic studies. Synthesis of the cyclic part was
      accomplished via the initial hydroboration-oxidation of Delta(5)-double bond. The
      key step in the synthesis of the side chain involved addition of (2S)-[3,4
      (2)H(6)]2,3-dimethylbutylphenyl sulfone to the corresponding C-22 aldehydes.

PMID- 15465107
TI  - Toxicity and antineoplastic effect of (24R)-1,24-dihydroxyvitamin D3 (PRI-2191).
AB  - Many efforts have been made to obtain active and less toxic Vitamin D analogs for
      new clinical applications. The results of previous studies demonstrated the
      efficacy and safety of topical treatment of psoriasis with one of these analogs,
      1,24-dihydroxyvitamin D(3), tacalcitol (1,24-(OH)(2)D(3)). In the present study,
      we evaluated the toxicity and antitumor effect of this analog. Lethal toxicity of
      1,24-(OH)(2)D(3) after s.c. injection was significantly lower than that of
      calcitriol. No significant differences were observed in the toxicity of the
      analogs when administered p.o. Calcium levels in the serum of mice treated with
      calcitriol were significantly higher (111%) than those in mice treated with 1,24
      (OH)(2)D(3) (89%) at 5 day after the first s.c. (10 microg/kg/day) administration
      in comparison to the control (healthy, untreated animals). Oral administration
      increased the calcium level by 78% for calcitriol and only to 47% over the
      control for 1,24-(OH)(2)D(3). Parallel administration of clodronate prevented the
      calcitriol- and 1,24-(OH)(2)D(3)-induced lethal toxicity and also prevented
      increase in calcium levels. Single therapy with calcitriol did not affect tumor
      growth in the 16/C mouse mammary cancer model. In contrary, 1,24-(OH)(2)D(3)
      alone reduced tumor volume to 41% of control. Cisplatin alone did not affect
      growth of 16/C tumor in these conditions. The growth of tumors in the presence of
      cisplatin was inhibited by 1,24-(OH)(2)D(3) but not by calcitriol. Interestingly,
      the inhibition of tumor growth in cisplatin-treated mice by 1,24-(OH)(2)D(3) was
      greater, than that observed in mice treated with this analog alone. In
      conclusion, 1,24-(OH)(2)D(3) revealed higher antitumor and lower calcemic
      activity and toxicity than calcitriol. Application of biphosphonates along with
      Vitamin D analogs is sufficient to overcome the calcemic and toxic side effects
      of the proposed treatment.

PMID- 15465109
TI  - Novel spironolactone-analogs as impurities in spironolactone.
AB  - Six novel spironolactone-analogs steroids (3-8) were isolated from spironolactone
      by using various chromatographic methods. Their structures were elucidated by
      spectrometric analysis. Two of the analogs (3 and 7) were confirmed by X-ray
      crystallography. The A-ring of compounds 3-7 is opened at C-2C-3 bond, and
      compound 7 is an organic polysulfide, which has a rare, nine-membered ring with a
      five sulfur atom bridge.

PMID- 15465110
TI  - Antigen-specific T cell functions are suppressed over the estrogen-dendritic cell
      indoleamine 2,3-dioxygenase axis.
AB  - Estrogen results in the suppression of experimental allergic encephalomyelitis
      (EAE), a frequently used experimental animal model of multiple sclerosis (MS).
      The mechanism by which estrogen acts in diseases with an autoimmune background is
      less clear. Here, we used splenic dendritic cells (DC) from the Lewis rats EAE
      model as target cells, and explored the pathway of estrogen in immune modulation.
      Estrogen did not affect the expression of MHC class II, CD80 and CD86 by DC, but
      inhibited the ability of DC to stimulate T cell proliferation and production of
      both Th1 and Th2 cytokines. This was accompanied by increased T cell apoptosis.
      Estrogen up-regulated DC to express indoleamine 2,3-dioxygenase (IDO) which can
      limit T cell responses. The effects of estrogen-exposed DC on T cell
      proliferation and apoptosis were partly abolished by addition of an IDO inhibitor
      (1-methyl-dl-tryptophan, 1-MT), indicating that estrogen-exposed DC induced IDO
      dependent T cell suppression. Our data support the hypothesis that the estrogen
      induced suppression of EAE, as well as the reduction in number of MS relapses
      observed during pregnancy, may be related to the estrogen-DC-IDO axis. This
      observation could open up a novel therapeutic target for influencing the course
      of MS and other diseases with an autoimmune diseases background.

PMID- 15465108
TI  - Estrogen induced changes in Akt-dependent activation of endothelial nitric oxide
      synthase and vasodilation.
AB  - OBJECTIVES: Acute administration of estrogen results in vasodilation and
      increased nitric oxide (NO) production. We examined the hypothesis that this is
      due to activation of Akt/PKB which subsequently increases eNOS activity. METHODS
      AND RESULTS: Treatment of bovine microvascular and human umbilical endothelial
      cells (HUVEC) with 17-beta-estradiol (E2) (10(-9) to 10(-5)M) increased
      phosphorylation of Akt within 1 min and this was followed by phosphorylation of
      eNOS. These effects were blocked by wortmannin, a PI(3)K inhibitor and the
      upstream activator of Akt. The estrogen receptor antagonist, ICI 182,780,
      inhibited eNOS phosphorylation. E2 increased calcium dependent NOS activity and
      nitrite production and this was inhibited by wortmannin and ICI 182,780. E2
      increased the vasodilatory response of aortic rings to acetylcholine and
      wortmannin blocked the effect. E2 (10(-9)M) dilated cerebral microvascular
      vessels under conditions of no flow, constant flow and increasing flow and this
      was blocked by wortmannin. Tamoxifen, a partial estrogen receptor antagonist,
      also dilated the microvessels. CONCLUSIONS: : E2 increases NO production through
      an Akt/PKB dependent pathway. This is associated with increased sensitivity to
      endothelial dependent dilation. In cerebral microvessels, E2 and tamoxifen
      produce significant dilation at low concentrations with and without acetylcholine
      induced stimulation of endothelial vasodilation.

PMID- 15465112
TI  - Simultaneous determination of dehydroepiandrosterone, its 7-hydroxylated
      metabolites, and their sulfates in rat brain tissues.
AB  - A method is described for simultaneous assessment of dehydroepiandrosterone
      (DHEA), its sulfate (DHEAS), and their 7-hydroxylated metabolites in cortex and
      subcortex of the rat brain. The procedure for determination of unconjugated
      steroids and DHEAS involved diethyl ether extraction of the homogenized tissue,
      solvent partition of the dry extract, and final quantification by specific
      radioimmunoassays. In addition, determination of 7-hydroxy-dehydroepiandrosterone
      sulfates required solvolysis, followed by high-performance liquid chromatography
      for separation of 7-hydroxylated metabolites from their precursor. The losses
      during this process were monitored by measurement of spiked radioactivity of
      [(3)H]testosterone or [(3)H]dehydroepiandrosterone sulfate. The content of
      dehydroepiandrosterone sulfate in both brain tissues was of the order of ten(s)
      nmol/g tissue irrespective its type (cortex or subcortex), while concentrations
      of other steroids were about 10 times lower in both tissues. In contrast to the
      ratio of sulfated/unconjugated DHEA, the levels of unconjugated 7-hydroxylated
      metabolites and their sulfates were close to each other. The reproducibility of
      the method with respect to coefficients of variation varied from 12 to 25%. An
      age-related decrease of sulfated dehydroepiandrosterone in the cortex of animals
      was also observed.

PMID- 15465111
TI  - Tamoxifen does not prevent the mobilization of body lipids elicited by oleoyl
      estrone.
AB  - Oleoyl-estrone is a powerful, slimming adipose tissue-derived signal that has
      biological effects widely opposed to those of its estrone moiety. The present
      experiment was designed to determine whether oleoyl-estrone effects on body
      energy are mediated by the estrogen receptor, blocked with the antagonist
      tamoxifen. Male Wistar rats were given daily oral doses of 10 micromol/kg d of
      oleoyl-estrone in oil containing 0 or 0.40 mg/kg d of tamoxifen. The data were
      compared with controls receiving only oil or 50 nmol/kg d of free estrone. After
      10 days, the rats were killed, and their body composition and plasma metabolites
      and hormones were analyzed. Rats receiving estrone increased their body energy
      and lipid content compared with controls. Both groups of oleoyl-estrone-treated
      rats lost body weight, energy, and lipid; the losses in the rats receiving
      tamoxifen alone were less marked than in those receiving oleoyl-estrone. No
      significant changes in plasma glucose or triacylglycerols were observed. The
      patterns of change of estrone sulphate, estradiol, and oleoyl-estrone were
      consistent with a noticeable hydrolysis of oleoyl-estrone. The lack of
      differences in the fat mass in oleoyl-estrone-treated rats irrespective of the
      presence of tamoxifen suggested that the estrogenic pathway was not responsible
      for the slimming effects observed. Thus, it can be concluded that oleoyl-estrone
      effects are not mediated through its conversion to estrone or estradiol acting
      through the estrogen receptor. Tamoxifen partly mimicked the slimming effects of
      oleoyl-estrone; this could be speculatively explained by tamoxifen acting through
      the oleoyl-estrone signalling pathway.

PMID- 15465113
TI  - Serum concentrations of androstenediol and androstenediol sulfate, and their
      relation to cytokine production during and after normal pregnancy.
AB  - Since it is known that androstenediol (ADIOL) has potent immunoregulatory
      effects, changes in ADIOL levels during and after pregnancy might affect the
      maternal immune system. We examined serum concentrations of ADIOL and
      androstenediol 3-sulfate (ADIOLS) together with IFN-gamma and IL-4 production
      levels during pregnancy and after delivery up to 10-11 months postpartum. The
      subjects were 73 normal pregnant, 76 normal postpartum, and 28 normal non
      pregnant women. ADIOL and ADIOLS were measured using EIA and GC/MS, respectively.
      The cytokine levels in the supernatant of whole-blood cultures stimulated with
      phorbol 12-myristate 13-acetate and ionomycin were measured using ELISA. ADIOL
      levels significantly decreased compared to non-pregnant levels in the first
      trimester (P < 0.05) and were reversed in the third trimester (P < 0.05). After
      pregnancy, ADIOL levels gradually declined, and a significant decrease was
      observed at 10-11 months postpartum (P < 0.05). ADIOLS levels were significantly
      lower in the third trimester (P < 0.05) and significantly higher at the first
      month postpartum (P < 0.001) compared to non-pregnant women. IFN-gamma and IL-4
      levels decreased during pregnancy and subsequently increased postpartum. On the
      other hand, we found significant negative correlations between ADIOL
      concentrations and production levels of IFN-gamma (P < 0.05) or IL-4 (P < 0.05).
      These findings suggest that ADIOL may be involved in modifying the maternal
      immune response during and after pregnancy.

PMID- 15465114
TI  - Endogenous estrogen receptor beta is transcriptionally active in primary ovarian
      cells from estrogen receptor knockout mice.
AB  - The estrogen receptor (ER) alpha is a hormone-inducible transcription factor that
      has a pivotal physiological role. Intriguingly, a clear and undisputed
      physiological function of the recently described ERbeta remains elusive, with the
      exception of the ovary where a cooperative role of ERalpha and ERbeta has been
      demonstrated. We have, therefore, investigated whether endogenous ERs, in
      particular ERbeta, act as ligand-inducible transcription factors in primary
      ovarian cells derived from wild-type, ERalpha or ERbeta knockout mice. Granulosa
      enriched cell fractions naturally expressing ERbeta and thecal cell fractions
      that express ERalpha were analyzed in transactivation assays using the
      vitellogenin A2 consensus estrogen response element and potent ER agonists
      diethylstilbestrol and S-indenestrol A. We studied also the potency-selective
      ERbeta agonist R-indenestrol A, the pure ERalpha agonist and ERbeta antagonist
      R,R-diethyl-tetrahydrochrysene and the pure ERalpha agonist propylpyrazole-triol.
      Using ER subtype-specific physiological cell models and these ER subtype-specific
      structural probes, we analyzed trans-activation of ERalpha and ERbeta. This
      analysis revealed that endogenously expressed ERbeta is indeed functional as a
      transcription factor, that it responds to estrogens appropriately, and that the
      ligands used are true ER subtype-specific probes in primary ovarian cells. In
      conclusion, this study demonstrates that endogenously expressed ERbeta is capable
      of regulating gene transcription independent of ERalpha.

PMID- 15465115
TI  - Non-invasive repeated measurement of urinary progesterone, 17beta-estradiol, and
      testosterone in developing, cycling, pregnant, and postpartum female mice.
AB  - Excretory samples from adult female mice were collected non-invasively during
      development, estrous cycling, pregnancy, and postpartum. In initial studies,
      urinary measures were statistically more dynamic over days than were fecal
      measures; thus subsequent studies focused on urine. Higher 17beta-estradiol
      levels were present in isolated females than in those exposed to males. In
      cycling females, urinary 17beta-estradiol was more variable than were measures of
      testosterone or progesterone, showing peaks with an approximate 5-day
      periodicity. When urinary estradiol and progesterone were monitored in
      conjunction with vaginal smear cell counts, patterns were idiosyncratic; most
      females showed distinct peaks in urinary steroids, not in clear synchrony with
      vaginal cell cornification. Levels of progesterone rose markedly during the first
      10 days of pregnancy, then declined before birth. Estradiol showed a substantial
      peak on days 7-8 of gestation in all females measured. Urinary testosterone was
      not dynamic during pregnancy, but rose in immediate prenatal and postpartum
      measures. During post-weaning, pre-pubertal development, urinary levels of
      progesterone remained constant but levels of estradiol rose substantially over
      time.

PMID- 15465116
TI  - A low-toxicity method for the separation of lanosterol and dihydrolanosterol from
      commercial mixtures.
AB  - We describe an inexpensive, low-toxicity and high-yielding method for the
      production of pure lanosterol and dihydrolanosterol from the commercially
      available mixture. Optimum conditions are presented for the one-pot production of
      the intermediate 24,25 vicinal diol of lanosterol acetate (via either epoxidation
      or hydroxyhalogenation) which is readily separated from the unreacted
      dihydrolanosterol acetate. The lanosterol diol can then be converted to pure
      (>97%) lanosterol. Hypophosphorous acid was used for both the conversion of the
      epoxide to the diol, and as a catalyst for the hydroxyhalogenation by N
      halosuccinimides of the olefinic bond.

PMID- 15465117
TI  - Regulation of bile acid synthesis under reconstructed enterohepatic circulation
      in rats.
AB  - Cholesterol 7alpha-hydroxylase (CYP7A1) is regulated by bile acids through the
      farnesoid X receptor (FXR) mechanism in a negative feedback fashion. However, the
      fact that CYP7A1 is down-regulated by intraduodenal administration of bile acid,
      but not by intravenous administration may not be explained only by this
      mechanism. The aim of this study was to establish a new rat model with
      reconstructed or simulated enterohepatic circulation to examine if intravenous or
      portal administration of bile acid can regulate CYP7A1. Under biliary drainage,
      taurocholate (0 or 6 micromol/h/100g body weight) was administered continuously
      for 48h into the duodenum (ID-0/ID-6), femoral vein (IV-0/IV-6), or portal vein
      (IP-0/IP-6) to create a condition in which biliary bile acids were continuously
      lost, and a similar dose of taurocholate was supplied to the liver
      simultaneously. CYP7A1 activity and mRNA expression of the ID-0 group were
      significantly increased compared with the no treatment (NT) group. CYP7A1
      activity and mRNA expression of the ID-6 group were suppressed significantly to
      41 and 46% of those of the ID-0 group, respectively. In the IV-6 and IP-6 groups,
      however, enzyme activity and mRNA expression were decreased slightly, but the
      suppression was not statistically significant. The results suggested that portal
      as well as intravenous administration of bile acids cannot suppress bile acid
      synthesis as effectively as intraduodenal administration. It was concluded that
      an unidentified regulatory factor other than the nuclear receptors may be
      involved in bile acid synthesis in vivo.

PMID- 15465118
TI  - How do sessile dioecious species cope with their males?
AB  - In terrestrial plants the segregation of male and female reproductions on
      different individuals results in the seed-shadow handicap: males do not disperse
      any seed so that the number of local patches reached by seeds is potentially
      reduced in dioecious populations in comparison to hermaphrodite populations. An
      analytical model, incorporating a lottery-based recruitment and dispersal
      stochasticity, was built. The spatially mediated cost of the seed-shadow handicap
      has been assessed considering the criterions for the invasion of a resident
      hermaphrodite species by a dioecious species and the reverse invasion, both
      species having the same demographic parameters but assuming a likely higher
      fecundity for dioecious females. The reciprocal invasion of a dioecious and
      hermaphrodite species differing only by their fecundity is never possible. The
      seed-shadow handicap disappears when the dispersal or survival rate is high
      enough. This latter point is due to dispersal stochasticity, which allows for the
      existence of empty patches. A low fecundity and an aggregated seed distribution
      increase dispersal stochasticity and increase the positive impact of a low
      mortality rate on the relative competitivity of dioecy and hermaphroditism.
      Adding a dispersal cost has a comparable effect but also requires higher
      dispersal rates for the dioecious invasion.

PMID- 15465119
TI  - Stochasticity, invasions, and branching random walks.
AB  - We link deterministic integrodifference equations to stochastic, individual-based
      simulations by means of branching random walks. Using standard methods, we
      determine speeds of invasion for both average densities and furthest-forward
      individuals. For density-independent branching random walks, demographic
      stochasticity can produce extinction. Demographic stochasticity does not,
      however, reduce the overall asymptotic speed of invasion or preclude continually
      accelerating invasions.

PMID- 15465120
TI  - The effect of unequal migration rates on FST.
AB  - Using the structured coalescent model, it is shown that unequal migration rates
      between different pairs of subpopulations can increase the value of Wright's
      coefficient F(ST) and its dependence on the mutation rate, and decrease the
      effective level of gene flow. Two specific models of population structure are
      considered: (i) an 'island model with barrier' where migration rates between
      subpopulations on the same side of the barrier are higher than migration rates
      between subpopulations on opposite sides of the barrier, and (ii) the two
      dimensional stepping-stone model with unequal migration rates in the two
      dimensions of the model.

PMID- 15465121
TI  - Slight differences among individuals and the unified neutral theory of
      biodiversity.
AB  - The unified neutral theory of biodiversity provides a very simple and
      counterintuitive explanation of species diversity patterns. By specifying
      speciation, community size and dispersal, and completely ignoring differences
      among individual organisms and species, it generates biodiversity patterns that
      remarkably resemble natural ones. Here I show that adding even slight differences
      among organisms generates very different patterns and predictions. In large
      communities with widespread dispersal, heritable differences in viability among
      individual organisms lead to biodiversity patterns characterised by the
      overdominance of a single species comprising organisms with relatively high
      fitness. In communities with local dispersal, the same differences produce rapid
      community extinction. I conclude that the unified neutral theory is not robust to
      slight deviations from its most controversial assumption.

PMID- 15465122
TI  - Competition between near and far dispersers in spatially structured habitats.
AB  - Competitive interactions and invasibility between short- and long-distance
      dispersal was investigated in a population on a heterogeneous landscape with
      spatial correlations in habitat types, and where the driving interaction between
      individuals is competition for space. Stochastic spatially explicit simulations
      were used, along with differential equation models based on pair approximations.
      Conditions under which either dispersal strategy can successfully invade the
      other were determined, as a function of the amount and clustering of suitable
      habitat and the relative costs involved in the two dispersal strategies. Long
      distance dispersal, which reduces intraspecific competition, is sometimes
      advantageous even where aggregation of suitable habitat would otherwise favor
      short-distance dispersal, although certain habitat distributions can lead to
      either strategy being dominant. Coexistence is also possible on some landscapes,
      where the spatial structure of the populations partitions suitable sites
      according to the number of suitable neighboring sites. Mutual competitive
      exclusion, where whichever strategy is established first cannot be invaded, is
      also possible. All of these results are observed even when there is no intrinsic
      difference in the two strategies' costs, such as mortality or competitive
      abilities.

PMID- 15465123
TI  - Ancestral inference on gene trees under selection.
AB  - The extent to which natural selection shapes diversity within populations is a
      key question for population genetics. Thus, there is considerable interest in
      quantifying the strength of selection. A full likelihood approach for inference
      about selection at a single site within an otherwise neutral fully linked
      sequence of sites is described here. A coalescent model of evolution is used to
      model the ancestry of a sample of DNA sequences which have the selected site
      segregating. The mutation model, for the selected and neutral sites, is the
      infinitely many-sites model where there is no back or parallel mutation at sites.
      A unique perfect phylogeny, a gene tree, can be constructed from the
      configuration of mutations on the sample sequences under this model of mutation.
      The approach is general and can be used for any bi-allelic selection scheme.
      Selection is incorporated through modelling the frequency of the selected and
      neutral allelic classes stochastically back in time, then using a subdivided
      population model considering the population frequencies through time as variable
      population sizes. An importance sampling algorithm is then used to explore over
      coalescent tree space consistent with the data. The method is applied to a
      simulated data set and the gene tree presented in Verrelli et al. (2002).

PMID- 15465124
TI  - Dispersal and the evolution of specialisation in a two-habitat type
      metapopulation.
AB  - Metapopulation theory for the evolution of specialisation is virtually absent. In
      this article, therefore, we study a metapopulation model for consumers with a
      fitness trade-off between two habitats. We focus on effects of habitat abundance,
      dispersal rate and trade-off strength on the evolution of specialisation under
      two types of trade-off. Adaptation affects either the intrinsic growth rates r or
      the carrying capacities K. Depending on dispersal rate and trade-off strength,
      evolution can result in one generalist, one specialist or two specialist types.
      Higher dispersal rate and a weaker trade-off favour the evolution of a
      generalist, for both trade-off structures. However, we also find differences
      between the two trade-off structures. Our results are qualitatively similar to
      analyses of two-patch models, suggesting that insights from such simpler models
      can be extrapolated to metapopulation models. Additional effects, however, occur
      because in classical metapopulations patch lifetime depends on extinction rate.
      Counterintuitively, this favours the evolution of specialisation when the trade
      off affects r.

PMID- 15465125
TI  - Evolution of social learning: a mathematical analysis.
AB  - Social learning is an important ability seen in a wide range of animals including
      humans. It has been argued that individual learning, social learning, and innate
      determination of behavior are favored by natural selection when environmental
      changes occur at short, intermediate, and long intervals, respectively. Only
      recently, however, has the hypothesis been examined by means of mathematical
      models. In this paper, we construct a simple model in which each organism uses
      one of three genetically determined strategies--it is an individual learner, a
      social learner or an "innate"--and the three types of organisms are in direct
      competition with each other. A reduced model, involving only the individual
      learners and innates, is effectively linear, and we show that by solving the
      eigenvalue problem of this reduced system we arrive at a good approximation to
      the global dynamics of the full model. We also study the effect of stochastic
      environmental changes and reversible mutations among the three strategies. Our
      results are consistent with the predictions of previous studies. In addition, we
      identify a critical level of environmental constancy below which only individual
      and social learners are present.

PMID- 15465126
TI  - A predator-prey model with infected prey.
AB  - A predator-prey model with logistic growth in the prey is modified to include an
      SIS parasitic infection in the prey with infected prey being more vulnerable to
      predation. Thresholds are identified which determine when the predator population
      survives and when the disease remains endemic. For some parameter values the
      greater vulnerability of the infected prey allows the predator population to
      persist, when it would otherwise become extinct. Also the predation on the more
      vulnerable prey can cause the disease to die out, when it would remain endemic
      without the predators.

PMID- 15465127
TI  - A model to explain the origin of a parasite sex-specific population structure.
AB  - A discrete time model was built to understand the origin of the sex-specific
      population structure of the human blood fluke, Schistosoma mansoni. We have
      estimated both male/female individual ratio and male/female genotype ratio of
      this parasite taking into account all the experimental published values on
      differential male and female life-history traits all along the life cycle. We
      considered in our model male and female life-history traits when both separated
      and together. The model showed that both male/female individual ratio and
      male/female genotype ratio of S. mansoni adults are biased toward males in each
      combination. This bias was more important in male/female genotype ratio than in
      the male/female individual ratio for the same initial values of cercarial
      development success. This model could explain the sex specific population
      structure of this parasite. Firstly, we showed that the male-biased individual
      ratio finds its origin in the vertebrate host. Secondly, we showed that the male
      biased genotype ratio originates prior to any interrelationship between adult
      worms and could generate by itself a sex-specific genetic structure.

PMID- 15465128
TI  - Microbial dechlorination of dioxins in estuarine enrichment cultures: effects of
      respiratory conditions and priming compound on community structure and
      dechlorination patterns.
AB  - The effect of respiratory conditions and priming compound on dechlorination
      patterns of heptachlorodibenzo-p-dioxins (HpCDD) was investigated using estuarine
      sediment-eluted cultures in the presence and absence of 20 mM sulfate, and 0.2
      microM 2-bromodibenzo-p-dioxin (2-BrDD) as a priming compound. Electron balance
      calculations based on fatty acid turnover, hydrogen production, and electron
      acceptor depletion/methane formation indicated that whereas fermentative
      processes dominated in sulfate-free incubations, sulfate-reduction was
      predominant in the sulfate-amended incubations. The dechlorination of
      1,2,3,4,6,7,8-HpCDD exhibited the following trends: (i) the relative yields of
      product formation did not exceed 30% and the presence of 2-BrDD increased the
      yield by up to 10%; (ii) sulfidogenic conditions resulted in a lower 2,3,7,8
      tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) formation, and the presence of 2-BrDD
      decreased the formation of 2,3,7,8-TCDD by additional 4-5-fold; (iii) the
      presence of 2-BrDD effected a predominance in lateral (2,3,7,8 positions) over
      peri (1,4,6,9 positions)-dechlorination. Denaturing gradient gel electrophoresis
      (DGGE) banding patterns indicated significant shifts of microbial community
      structure in response to terminal electron accepting processes as well as to the
      presence of the priming compound. The latter resulted in a similar community
      structure independent of dioxin spike, indicating that subsets of populations in
      the sediment are capable of exploiting the new niche provided by the priming
      compound.

PMID- 15465129
TI  - Acute toxicity of tributyltin to the Caprellidea (Crustacea: Amphipoda).
AB  - In order to compare the acute toxicity of tributyltin (TBT) between sexes, five
      species of caprellid amphipods were exposed to seven levels (0, 0.001, 0.01, 0.1,
      1, 10 and 100 microg l(-1)) of TBT for 48 h at 20 degrees C. The 48-h LC50 values
      in male and female were 1.3-6.4 microg TBTCl l(-1) and 1.2-8.6 microg TBTCl l(
      1), respectively. No sex-specific differences of the acute toxicity of TBT were
      observed in the caprellids. These findings suggest that the risk of survival in
      response to exposure to TBT between sexes is similar in the caprellids.

PMID- 15465130
TI  - Sublethal toxicity of orchard stormwater runoff in Sacramento splittail
      (Pogonichthys macrolepidotus) larvae.
AB  - The sublethal effects of stormwater runoff from sections of a plum orchard
      treated with esfenvalerate or diazinon were evaluated in 7-day-old Sacramento
      splittail (Pogonichthys macrolepidotus) larvae. Fish were exposed to eight runoff
      samples using the USEPA standard static renewal method for 96 h acute toxicity
      testing, then transferred to clean water for three-month to assess the survival,
      growth, histopathological abnormalities, and heat stress proteins (hsp). No
      significant mortality was observed at 96 h in exposed fish. At one week,
      histopathological abnormalities included severe glycogen depletion, cytoplasmic
      protein droplets, vacuolar degeneration, and cell necroses in liver of all
      exposure groups. Pyknotic nerve cells were seen in brain of one exposure group.
      Significantly higher cumulative mortality, lower condition factor, and elevated
      hsp60 and hsp70 levels (p < 0.05) were occurred in several exposure groups. No
      histopathological abnormalities were observed after three months in any exposure
      group. This study confirms that standard acute toxicity tests have underestimated
      the toxicity of stormwater runoff, and although splittail larvae survived the 96
      h exposure, they exhibited reduced survival and growth and showed signs of
      cellular stress even after a three month recovery period.

PMID- 15465131
TI  - Impact of exploratory offshore drilling on benthic communities in the Minerva gas
      field, Port Campbell, Australia.
AB  - Changes to benthic infauna caused by exploratory gas drilling operations in the
      Minerva field were examined experimentally using a BACI (before, after, control,
      impact) design. Analysis of 72 x 0.1 m2 Smith-McIntyre grab samples obtained from
      one pre-drilling and three post-drilling periods yielded a diverse fauna
      consisting of 196 invertebrate species and 5035 individuals. Changes to benthic
      community structure were assessed using ANOVA and nonmetric multidimensional
      scaling (MDS). The abundances of two common species (Apseudes sp. 1 and
      Prionospio coorilla) decreased significantly at the well-head site immediately
      after drilling. The size of these reductions in abundance ranged between 71% and
      88%, and persisted for less than 4 months after drilling. A third common species
      (Katlysia sp. 1) increased in abundance 200 m east of the well-head following
      drilling. Most species occurred at densities too low to be analysed individually
      and so were pooled at higher taxonomic levels. Changes in the abundance of
      species aggregated by phylum varied, but significant declines in the most
      abundant phyla (Crustaceans and Polychaetes) of 45-73% were observed at all sites
      within a 100 m radius of the well-head following drilling. In most cases these
      changes became undetectable four months after drilling following species
      recruitments. MDS ordinations confirm that drilling related changes to benthic
      community structure are most pronounced at stations located closest to the well
      head. Additionally, the ordinations indicate that modified communities persist at
      the well-head for more than 11 months following exploratory drilling.

PMID- 15465132
TI  - Effects of salinity and clay type on oil-mineral aggregation.
AB  - Effects of salinity and clay type on the aggregation process of crude oil and
      clay particles (oil-mineral aggregates--OMA) were studied in the laboratory. OMA
      were generated by shaking various oil/clay mixtures in water at 20 degrees C and
      at a pre-determined energy level. Shape, median and maximum sizes, size
      distribution and concentration of oil droplets forming OMA were measured using
      epi-fluorescence microscopy. Results showed that the median and maximum sizes and
      the concentration of mineral-stabilized droplets increase rapidly when salinity
      increases from zero to a critical aggregation salinity in the range of 1.2-3.5
      ppt. The magnitude of the increase of droplet size is controlled by clay type,
      while the increase of droplet concentration is influenced by oil type. Size
      distributions of oil droplets are self-similar, but their magnitudes depend on
      salinity and oil type. The effect of salinity on droplet size distribution is
      strongly influenced by clay type. Empirical relationships are derived to
      calculate concentration and size distribution of mineral-stabilized droplets.

PMID- 15465133
TI  - Comparison of sampling devices for the determination of polychlorinated biphenyls
      in the sea surface microlayer.
AB  - Over 30 sea surface microlayer (SML) samples from two contrasting sites in the
      North Western Mediterranean -- Barcelona (Spain) and Banyuls-sur-Mer (France) --
      were collected using three different sampling devices, namely, glass plate, metal
      screen (MS) and a surface slick sampler (SS), and compared with the corresponding
      underlying water (16 samples). The distributions of 41 polychlorinated biphenyl
      congeners (PCBs) were determined in the different phases: particulate (1.17-10.8
      SigmaPCB ng L(-1)), truly dissolved (0.080-16.7 SigmaPCB ng L(-1)) and colloidal
      matter (1.17-43.0 SigmaPCB ng L(-1)), being the last two estimated from the
      analysis of the apparently dissolved phase. Concentrations of PCBs in the SML
      were higher than those in the underlying water (ULW), giving rise to enrichment
      factors (EF=[C](SML)/[C](ULW)) up to first-order of magnitude. The ANOVA
      statistical approach was used to assess differences of bulk data (e.g. dissolved
      organic carbon, DOC; particulate organic carbon, POC; suspended particulate
      matter, SPM) among sampling devices, whilst p-tailed t paired tests were used in
      order to compare the enrichments obtained for each sampling date. In this
      respect, no significantly different enrichment factors were found among sampling
      devices (p < 0.05), although the surface SS showed lower enrichments, probably
      due to the dilution of the SML with the ULW during sampling. The MS seemed to be
      the most suitable device for the determination of PCBs in the SML in terms of
      sampling efficiency under a variety of meteorological conditions.

PMID- 15465135
TI  - Multidisciplinary approaches for investigating the mechanisms of hippocampus
      dependent memory: a focus on inbred mouse strains.
AB  - Inbred mouse strains differ in genetic makeup and display diverse learning and
      memory phenotypes. Mouse models of memory impairment can be identified by
      examining hippocampus-dependent memory in multiple strains. These mouse models
      may be used to establish the genetic, molecular, and cellular correlates of
      deficits in learning or memory. In this article, we review research that has
      characterized hippocampal learning and memory in inbred mouse strains. We focus
      on two well-established behavioral tests, contextual fear conditioning and the
      Morris water maze (MWM). Selected cellular and molecular correlates of good and
      poor memory performance in inbred strains are highlighted. These include
      hippocampal long-term potentiation, a type of synaptic plasticity that can
      influence hippocampal learning and memory. Further methods that might help to
      pinpoint the anatomical loci, and genetic and cellular/molecular factors that
      contribute to memory impairments in inbred mice, are also discussed.
      Characterization of inbred mouse strains, using multidisciplinary approaches that
      combine cellular, genetic, and behavioral techniques, can complement directed
      mutagenesis to help identify molecular mechanisms for normal and abnormal memory
      functions.

PMID- 15465136
TI  - A reaffirmation of the retrosplenial contribution to rodent navigation: reviewing
      the influences of lesion, strain, and task.
AB  - Retrosplenial cortex (RS) is situated both anatomically and functionally between
      neocortical and limbic structures involved in spatial navigation. Initial
      anatomical, electrophysiological and behavioural evidence in both humans and
      rodents strongly suggested a role for RS in spatial navigation as well. Later
      studies using more selective cytotoxic lesions in rodents, however, cast doubt on
      earlier RS studies by failing to find spatial deficits following RS lesions.
      Contrasting reports from behavioural results on spatial tasks following RS damage
      have continued to be reported during the past decade. That RS does indeed
      contribute spatial behaviour even in rodents has been recently reaffirmed. The
      ambiguity surrounding RS is shown to result from differences in the choice of
      spatial tasks and rat strains between studies that find RS deficits and those
      that do not. The reconciliation of behavioural results following RS lesions
      strengthens the view that RS forms a part of the neural circuitry that underlies
      spatial navigation.

PMID- 15465134
TI  - Mapping brain function in freely moving subjects.
AB  - Expression of many fundamental mammalian behaviors such as, for example,
      aggression, mating, foraging or social behaviors, depend on locomotor activity. A
      central dilemma in the functional neuroimaging of these behaviors has been the
      fact that conventional neuroimaging techniques generally rely on immobilization
      of the subject, which extinguishes all but the simplest activity. Ideally,
      imaging could occur in freely moving subjects, while presenting minimal
      interference with the subject's natural behavior. Here we provide an overview of
      several approaches that have been undertaken in the past to achieve this aim in
      both tethered and freely moving animals, as well as in nonrestrained human
      subjects. Applications of specific radiotracers to single photon emission
      computed tomography and positron emission tomography are discussed in which brain
      activation is imaged after completion of the behavioral task and capture of the
      tracer. Potential applications to clinical neuropsychiatry are discussed, as well
      as challenges inherent to constraint-free functional neuroimaging. Future
      applications of these methods promise to increase our understanding of the neural
      circuits underlying mammalian behavior in health and disease.

PMID- 15465137
TI  - The value of spontaneous alternation behavior (SAB) as a test of retention in
      pharmacological investigations of memory.
AB  - Because of its reliance on memory, the tendency for rats, mice and other animals
      to alternate successive choices of T- or Y-maze arms has assumed considerable
      popularity in pharmacological studies of spatial memory as a quick and simple
      measure of retention that avoids the need for extensive training and the use of
      conventional reinforcers. Two forms of this tendency have been utilized, namely
      two-trial and continuous spontaneous alternation behavior (SAB). However, as the
      behavior can also reflect drug-related changes in sensory/attentional,
      motivational and performance processes, SAB should not be unquestionably accepted
      as a measure of memory alone. While assessments of post-acquisition drug effects
      on longer term memory may be possible through the appropriate timing of drug
      administration, this is more problematic if SAB is used as a measure of shorter
      term memory. Even though SAB can be a useful index of responsiveness to novelty,
      its value as a measure of retention is less certain. In this latter respect, a
      possible alternative to SAB testing might be the recently developed form of the
      related procedure, responsiveness to change.

PMID- 15465138
TI  - The role of norepinephrine in epilepsy: from the bench to the bedside.
AB  - This article provides a brief review of the role of norepinephrine (NE) in
      epilepsy, starting from early studies reproducing the kindling model in NE
      lesioned rats, through the use of specific ligands for adrenergic receptors in
      experimental models of epilepsy, up to recent advances obtained by using
      transgenic and knock-out mice for specific genes expressed in the NE system. Data
      obtained from multiple experimental models converge to demonstrate the
      antiepileptic role of endogenous NE. This effect predominantly consists in
      counteracting the development of an epileptic circuit (such as in the kindling
      model) rather than increasing the epileptic threshold. This suggests that NE
      activity is critical in modifying epilepsy-induced neuronal changes especially on
      the limbic system. These data encompass from experimental models to clinical
      applications as recently evidenced by the need of an intact NE innervation for
      the antiepileptic mechanisms of vagal nerve stimulation (VNS) in patients
      suffering from refractory epilepsy. Finally, recent data demonstrate that NE loss
      increases neuronal damage following focally induced limbic status epilepticus,
      confirming a protective effect of brain NE, which has already been shown in other
      neurological disorders.

PMID- 15465139
TI  - Testing the importance of the retrosplenial navigation system: lesion size but
      not strain matters: a reply to Harker and Whishaw.
AB  - In their review on the retrosplenial cortex Harker and Whishaw [Neurosci Biobehav
      Rev, 2004] claim that there is continued disagreement over the importance of this
      region for navigation. They argue that discrepancies in the published effects of
      retrosplenial lesions reflect two principal variables, choice of rat strain and
      choice of spatial task. In this reply, evidence is provided showing that Harker
      and Whishaw [Neurosci Biobehav Rev, 2004] have created a misleading impression
      and, in fact, there is a clear consensus that the rat retrosplenial cortex is
      necessary for navigation. Likewise, there is no dispute that the effects of
      retrosplenial lesions will differ for different tests of spatial learning. While
      Harker and Whishaw [Neurosci Biobehav Rev, 2004] also conclude that choice of rat
      strain has a critical impact on whether a lesion-induced deficit is found, a
      comprehensive review of the published data shows no systematic strain difference.
      There is, however, growing evidence that when interpreting the effects of
      retrosplenial lesions, account should be given of the lesion method and its
      interaction with lesion size.

PMID- 15465140
TI  - Gastro-intestinal and genito-urinary morbidity after 3D conformal radiotherapy of
      prostate cancer: observations of a randomized trial.
AB  - BACKGROUND AND PURPOSE: The late morbidity of a randomized study was analyzed
      after a follow up of 2 years. The difference in intestinal morbidity was analyzed
      as a function of the treatment arm and dose volume parameters. The correlation
      with acute toxicity and (pre-existing) bowel complaints was investigated.
      PATIENTS AND METHODS: 266 T1-4N0M0 prostate cancer patients were randomized for
      conventional (open fields) and 3D conformal radiotherapy using beams eye view
      blocked fields with the same dose (66 Gy) and gross target volume-planning target
      volume margin (15 mm). Apart from the RTOG toxicity scoring system a patient self
      assessment questionnaire was used to obtain detailed information on morbidity.
      RESULTS: At 2 years there is only a trend for less rectal toxicity (grade >/=1)
      in favor of the conformal radiotherapy (grade 1, 47 versus 40% and grade 2, 10
      versus 7% for conventional and conformal radiotherapy, respectively (P=0.1). A
      significant relation was found between late rectal toxicity (grade >/=1) and the
      volume of the anus and rectum exposed to >/=90% tumor dose (TD). A highly
      significant relationship is observed between acute rectum and anal toxicity and
      late rectal toxicity. The patient self-assessment questionnaire analysis revealed
      that patients are most bothered by compliance related symptoms like urgency,
      soiling and fecal loss. In a multivariate analysis, all other variables loose
      significance, when anal volume exposed to >/=90% TD and pre-treatment defaecation
      frequency are accounted for. Late anal toxicity is low and related only to acute
      anal toxicity. Late bladder toxicity is related solely to pre-treatment frequency
      and overall urological symptoms. The incidence of grade 2 toxicity increases with
      a factor 2.5-4 when (stool or urine) frequency is unfavorable at the start of
      treatment. CONCLUSIONS: Conformal radiotherapy at the dose level of 66 Gy does
      not significantly decrease the incidence of rectal, anal and bladder toxicity
      compared to conventional radiotherapy. There is a significant relationship
      between acute and late toxicity and the anal volume exposed to 90% TD. Intestinal
      (and urological) symptoms at start have a major impact on late toxicity.

PMID- 15465141
TI  - Quality assurance of the 22961 EORTC trial. A phase III study of the optimal
      combination of hormonal adjuvant treatment by LHRH analogue and radiation therapy
      for the management of locally advanced prostate cancer: the dummy run.
AB  - PURPOSE: The EORTC trial 22961, opened in 1997, was designed to investigate the
      optimal combination of hormonal adjuvant treatment by LHRH analogue and radiation
      therapy for the management of locally advanced prostate cancer. A dummy run was
      established to assess centre compliance to the radiotherapy protocol. MATERIALS
      AND METHODS: Medical and anatomical data obtained from 37 CT slices (5mm
      thickness) of an eligible patient were sent to 19 participating centres, which
      were asked to complete a questionnaire according to their practice and plan a
      theoretical radiotherapy treatment. The Planning Target Volume 1 (PTV1) should
      include prostate, seminal vesicles, internal iliac lymph nodes and inferior part
      of common iliac lymph nodes (extended pelvic fields). Centres which usually
      irradiate with small pelvic fields (N0 patients), were allowed to include the
      prostate, seminal vesicles and internal iliac lymph nodes plus a safety margin of
      2 cm. For the Planning Target Volume 2 (PTV2), a safety margin of 1.5 to 2 cm
      should be around the prostate and seminal vesicles. Checks included patient
      positioning, treatment simulation, target volume definition, treatment set-up and
      clinical controls during treatment. RESULTS: Eleven institutions with actual 81%
      of patients' accrual in the protocol have responded. All centres used a supine
      treatment position and positioning lasers for the set-up, while 73 and 45% of the
      centres performed cystograms and used rectal contrast, respectively. Among the
      participating centres, 45% and 55% used blocks and MLC, respectively, to treat
      patients. Extended pelvic fields in terms of PTV1 were used by 63% of the
      centres. The remaining centres treated a small PTV1 with a 10-20 mm margin around
      to CTV1. All centres defined PTV2 according to protocol guidelines. Doses to PTV1
      and PTV2 were correctly prescribed. It was difficult to assess the treated
      volumes due to a lack of standardisation in DVH calculations. CONCLUSION: In
      general, centres participating in the dummy run adhered to the guidelines. The
      dummy run enhances the reliability of the conclusions of the trial.

PMID- 15465142
TI  - Fitting late rectal bleeding data using different NTCP models: results from an
      Italian multi-centric study (AIROPROS0101).
AB  - BACKGROUND AND PURPOSE: Recent investigations demonstrated a significant
      correlation between rectal dose-volume patterns and late rectal toxicity. The
      reduction of the DVH to a value expressing the probability of complication would
      be suitable. To fit different normal tissue complication probability (NTCP)
      models to clinical outcome on late rectal bleeding after external beam
      radiotherapy (RT) for prostate cancer. PATIENTS AND METHODS: Rectal dose-volume
      histograms of the rectum (DVH) and clinical records of 547 prostate cancer
      patients (pts) pooled from five institutions previously collected and analyzed
      were considered. All patients were treated in supine position with 3 or 4-field
      techniques: 123 patients received an ICRU dose between 64 and 70 Gy, 255 patients
      between 70 and 74 Gy and 169 patients between 74 and 79.2 Gy; 457/547 patients
      were treated with conformal RT and 203/547 underwent radical prostatectomy before
      RT. Minimum follow-up was 18 months. Patients were considered as bleeders if
      showing grade 2/3 late bleeding (slightly modified RTOG/EORTC scoring system)
      within 18 months after the end of RT. Four NTCP models were considered: (a) the
      Lyman model with DVH reduced to the equivalent uniform dose (LEUD, coincident
      with the classical Lyman-Kutcher-Burman, LKB, model), (b) logistic with DVH
      reduced to EUD (LOGEUD), (c) Poisson coupled to EUD reduction scheme and (d)
      relative seriality (RS). The parameters for the different models were fit to the
      patient data using a maximum likelihood analysis. The 68% confidence intervals
      (CI) of each parameter were also derived. RESULTS: Forty six out of five hundred
      and forty seven patients experienced grade 2/3 late bleeding: 38/46 developed
      rectal bleeding within 18 months and were then considered as bleeders The risk of
      rectal bleeding can be well calculated with a 'smooth' function of EUD (with a
      seriality parameter n equal to 0.23 (CI 0.05), best fit result). Using LEUD the
      relationship between EUD and NTCP can be described with a TD50 of 81.9 Gy (CI 1.8
      Gy) and a steepness parameter m of 0.19 (CI 0.01); when using LOGEUD, TD50 is
      82.2 Gy and k is 7.85. Best fit parameters for RS are s=0.49, gamma=1.69,
      TD50=83.1 Gy. Qualitative as well as quantitative comparisons (chi-squared
      statistics, P=0.005) show that the models fit the observed complication rates
      very well. The results found in the overall population were substantially
      confirmed in the subgroup of radically treated patients (LEUD: n=0.24 m=0.14
      TD50=75.8 Gy). If considering just the grade 3 bleeders (n=9) the best fit is
      found in correspondence of a n-value around 0.06, suggesting that for severe
      bleeding the rectum is more serial. CONCLUSIONS: Different NTCP models fit quite
      accurately the considered clinical data. The results are consistent with a rectum
      'less serial' than previously reported investigations when considering grade 2
      bleeding while a more serial behaviour was found for severe bleeding. EUD may be
      considered as a robust and simple parameter correlated with the risk of late
      rectal bleeding.

PMID- 15465143
TI  - Factors predicting for urinary morbidity following 125iodine transperineal
      prostate brachytherapy.
AB  - PURPOSE: To assess factors related to the risk of acute urinary retention and
      other morbidity indices in patients undergoing transperineal seed implantation of
      the prostate. MATERIALS AND METHODS: One hundred and seventy-three consecutive
      patients treated with (125)Iodine transperineal interstitial permanent prostate
      brachytherapy (TIPPB) were evaluated. Various demographic, pathological,
      symptomatic, urodynamic and dosimetric values were assessed in relation to the
      incidence of acute urinary retention as well as the International Prostate
      Symptom Score (IPSS) dynamics. Patients were routinely placed on alpha-blockade
      postimplant. Dosimetry was based on CT scan one month postimplant. RESULTS: Acute
      urinary retention developed in thirty-four patients (19.7%), at a median time of
      four days. Peak urinary flow rate was the only independent factor which varied
      significantly between those suffering retention and those not (median of 16 and
      19.5 ml/s respectively, P=0.005). Median preimplant IPSS was 4.0, with a median
      peak of 16 at 3 months. Actuarial median time to return to baseline IPSS was at
      15 months. The peak IPSS above preimplant levels was correlated significantly in
      multivariate analysis with the number of seeds implanted superior to the
      physician-nominated anatomical base level of the prostate (P<0.009), as well as
      lower preimplant IPSS values. CONCLUSIONS: In our series, preimplant urinary flow
      rate was the most important factor predictive of postimplant acute urinary
      retention. The patients' risk of having heightened IPSS change following
      implantation was correlated to a lower preimplant IPSS and an increased number of
      seeds implanted above the level of the prostatic base, possibly reflecting
      bladder base rather than urethral irritation in the development of acute urinary
      morbidity.

PMID- 15465144
TI  - Clinical and physical determinants for toxicity of 125-I seed prostate
      brachytherapy.
AB  - BACKGROUND AND PURPOSE: To assess acute as well as long-term toxicity after
      permanent prostate seed implantation. To find predictive clinical or dosimetric
      factors for side effects in order to work out strategies for improvement.
      PATIENTS AND METHODS: A group of 174 patients with localised prostate cancer was
      treated with permanent seed implantation between 1999 and 2001, either alone (140
      patients) or in combination with external radiotherapy (34 patients). For the
      majority (114/174, i.e. 66%) a CT was performed four weeks after implantation and
      analysed in the planning system VariSeed. In the postimplant analysis, dosimetric
      descriptors (doses, volumes) were determined for the prostate and rectum and
      compared with the intraoperative values. In addition, a questionnaire was sent to
      all patients to assess and quantify acute and chronic toxicity (urinary, rectal,
      sexual) and the impact on subjective acceptance and quality of life (return rate
      of questionnaires 83%). The derived score changes were correlated with clinical
      and dosimetric factors. RESULTS: In the mono-brachytherapy group 14% (16/140)
      required a bladder catheter, of them 8% (9/140) with a manifest urinary
      obstruction. Long-term rectal toxicity (<5%) and impairment of potency (<30%) are
      moderate and obviously below other treatment options. Urinary toxicity is
      dominant with an overall long-term dysuria up to 30% (at a mean observation
      interval of ten months), and a significant trend to decline with follow-up time.
      Conversely, the erectile function tends to deteriorate with follow-up time.
      Nevertheless, quality of life is not significantly reduced and acceptance is
      high. Our analysis suggests that the main factor for urinary toxicity and
      impaired erectile function is the dose load to larger portions of the prostate
      (D(50)>240 Gy), which appears to be attributed to unnecessarily high numbers of
      seeds (for a fixed activity per seed) and needles. The rectal toxicity is
      correlated with the high dose regions in the rectum (>/=145 Gy). Urinary toxicity
      is lower for combined-brachytherapy, while rectal toxicity and impairment of
      potency are slightly higher. CONCLUSIONS: Toxicity spectrum and quality of life
      after permanent seed implantation for early prostate cancer are acceptable for
      nearly all patients (98%). To further improve tolerance we should attempt to
      achieve a better dose homogeneity, i.e. by reducing D(50). Therefore, special
      attention should be given to D(50) during the real-time planning process. The
      necessity of more homogeneous dose distributions might imply a reduction of the
      activity per seed, e.g. from 0.7 mCi down to 0.6 mCi.

PMID- 15465145
TI  - Quality of permanent prostate implants using automated delivery with
      seedSelectron versus manual insertion of RAPID Strands.
AB  - BACKGROUND AND PURPOSE: To compare the quality of manually inserted RAPID Strand
      implants with automatically inserted selectSeed implants using volumetric and
      dosimetric parameters. PATIENTS AND METHODS: Patients with T1 to T2 prostate
      carcinoma were treated with brachytherapy. The (125)I seeds were implanted in the
      prostate in three different ways: manual insertion of RAPID Strands (R);
      insertion of selectSeeds using the seedSelectron (S); a combination of both
      techniques: manual insertion of RAPID Strands in the left half of the prostate
      and insertion of selectSeeds with the seedSelectron in the right half of the
      prostate (RS). The comparison is based on implant and target specific parameters.
      The implant specific parameters, V(100), homogeneity index (HI), and natural dose
      ratio (NDR), were determined at the time of implantation and four weeks later. MR
      images taken four weeks after the implantation were used for the calculation of
      the target specific parameters: D(90), HI, external index (EI), and conformation
      number (CN). RESULTS: We found no significant difference between the groups of
      implants (R, S, RS) for the implant specific parameters V(100), HI, and NDR at
      t(0) and neither at t(4w). For each group, the V(100) values decreased
      significantly with time between t(0) and t(4w). The target specific parameters
      D(90), HI, EI and CN were not significantly different between the groups. For the
      group of patients with both RAPID Strands and selectSeeds, we found a significant
      difference in D(90) between both halves of the prostate. CONCLUSIONS: The
      dosimetry parameters of a newly introduced implant technique using an automatic
      seed afterloader were not significantly different from the parameters of a manual
      insertion technique using RAPID Strands. Since either technique has its
      advantages and disadvantages regarding seed migration, physics quality assurance,
      efficiency, logistics, and ease of use, it was decided to use both techniques and
      to continue evaluations.

PMID- 15465146
TI  - Trans-perineal implantation of radio-opaque treatment verification markers into
      the prostate: an assessment of procedure related morbidity, patient acceptability
      and accuracy.
AB  - On-line imaging of prostate markers can be used to compensate for errors in
      radiation delivery. This study assessed the patient acceptability and morbidity
      associated with the trans-perineal route of implantation. A minority experienced
      acute pain or bleeding. Placement was accurate in all but one subject. An
      operator related learning curve exists. Although this is an invasive procedure
      most patients found it acceptable. Implementation for routine clinical practice
      is feasible.

PMID- 15465147
TI  - Performing daily prostate targeting with a standard V-EPID and an automated radio
      opaque marker detection algorithm.
AB  - Online prostate positioning using gold markers and a standard video-based
      electronic portal imaging device is reported. The average systematic (random)
      errors have been reduced from 2.1 mm (2.7 mm) to 0.5 mm (1.5 mm) in AP direction,
      1.1 mm (1.7 mm) to 0.7 mm (1.2 mm) SI and 1.2 mm (1.7 mm) to 0.6 mm (1.3 mm) LR.

PMID- 15465148
TI  - A comparison of forward and inverse planned conformal, multi segment and
      intensity modulated radiotherapy for the treatment of prostate and pelvic nodes.
AB  - BACKGROUND AND PURPOSE: Full inverse planned intensity modulated radiotherapy
      (IMRT) may be indicated to treat concave targets like prostate and pelvic nodes,
      because concave dose distributions cannot be generated with conformal
      radiotherapy (CRT). We investigated whether this concave dose distribution can be
      produced using simplified forward planned multi segment radiotherapy (MSRT).
      PATIENTS AND METHODS: CRT, MSRT and IMRT dose distributions were calculated and
      compared for five patients treated in our current IMRT prostate and pelvic node
      dose escalation trial. The same beam arrangement was used for CRT, MSRT and IMRT,
      increasing the number of segments. The MSRT concave dose distribution was
      realised regarding left and right pelvic nodes as two separate targets. The IMRT
      dose distribution had been used to treat the patients using a step and shoot
      delivery. RESULTS: Contrary to CRT, forward planned MSRT concave dose
      distributions had improved target coverage at lower or equivalent bowel doses
      than inverse planned IMRT. The five MSRT beams had a maximum of three segments
      per beam. Both lateral beams had two segments to deliver the two dose levels to
      prostate and nodes. The posterior field needed a third segment to avoid using a
      central block. The two anterior oblique beams needed a third segment to account
      for the different beam weighting because the nodes were irradiated partially
      using four and partially using five beams. Inverse planned IMRT used up to 15
      segments in any one beam, with an average of 11.4 per beam. CONCLUSIONS: Concave
      dose distributions for prostate and pelvic node treatment were generated using
      forward planned multi segment techniques. The plans met clinical constraints used
      in our IMRT protocol. MSRT presented a significant advantage over both CRT and
      IMRT.

PMID- 15465149
TI  - Anatomy based inverse planning in HDR prostate brachytherapy.
AB  - The purpose of this study is to evaluate anatomy based inverse planning as
      implemented in PLATO BPS 14.2 for planning of HDR prostate implants. Six patients
      were analysed. The dose distributions were optimized using geometric optimization
      followed by graphical optimization (GO), anatomy based inverse planning or
      standard inverse optimization (SIO), tuned inverse optimization (TIO) and tuned
      inverse optimization followed by graphical optimization (GOTIO). The mean target
      coverage was 93+/-4%, 53+/-11%, 74+/-8%, 90+/-3%, respectively, for GO, SIO, TIO
      and GOTIO. The conformal index COIN was 0.74+/-0.02, 0.43+/-0.15 and 0.77+/-0.07,
      respectively, for GO, SIO and GOTIO. Improved dose homogeneity was found when
      comparing GOTIO with GO.

PMID- 15465150
TI  - Dosimetric verification of a commercial collapsed cone algorithm in simulated
      clinical situations.
AB  - BACKGROUND AND PURPOSE: This work reports a detailed study carried out in two UK
      radiotherapy centres of the dosimetric accuracy of the collapsed cone algorithm
      of a commercial treatment planning system (Helax-TMS) in simulated clinical
      situations. MATERIALS AND METHODS: Initially the accuracy of the collapsed cone
      algorithm in homogeneous media is evaluated for an extensive set of simple and
      complex fields. Water, lung and bone substitute epoxy resin material were then
      used to assess the algorithm in inhomogeneous media and compare its accuracy with
      the pencil beam algorithm currently in clinical use. Finally a semi-anatomic
      phantom and an anthropomorphic phantom were employed to assess the dosimetric
      accuracy using simulated clinical set ups. Thermoluminescence dosimeter (TLD)
      measurements were made with the anthropomorphic phantom and ionisation chambers
      otherwise. Nominal 4, 6 and 15 MV photon beams were studied. RESULTS: For most
      homogeneous cases agreement between measured and calculated dose is within +/-2%
      or +/-2 mm. In cases with heterogeneities and simulated clinical situations it is
      observed that the accuracy is also generally within +/-2% or +/-2 mm. Specific
      instances where the difference between measured and calculated values exceed this
      are highlighted. CONCLUSIONS: It can be concluded that in clinical treatment
      planning situations where lung is present the collapsed cone algorithm should be
      considered in preference to pencil beam algorithms normally used but that there
      may still be some discrepancy between calculations and measurement.

PMID- 15465151
TI  - Feasibility study of entrance in vivo dose measurements with mailed
      thermoluminescence detectors.
AB  - BACKGROUND AND PURPOSE: The aim of this work is to set-up mailed entrance in vivo
      dosimetry by means of thermoluminescence dosimeters (TLDs) in the form of LiF
      powder in order to assess the overall accuracy of patient treatment delivery by
      comparing the doses delivered to patients with the doses calculated by the
      treatment planning system (TPS) in different institutions. PATIENTS AND METHODS:
      Two millimeter thick copper (for 6 MV photon beams) and 1.3 mm thick aluminium
      (for (60)Co gamma beams) build-up caps are developed. The characteristics of
      these build-up caps are tested by phantom measurements: the response of the TLD
      inside the build-up cap is compared to the ionisation chamber (IC) signal in the
      same irradiation conditions. A pilot study using the copper build-up cap is
      performed on 8 patients, treated with a 6 MV photon beam at the radiotherapy
      department of the University Hospital of Leuven. Additionally, a first run of
      mailed entrance in vivo dosimetry is performed by 18 radiotherapy centres in
      Europe. RESULTS: For 80 different phantom set-ups using copper and aluminium
      build-up caps, the mean TLD dose compared to the IC dose is 0.993+/-0.015 (1SD).
      Regarding the patient measurements in the radiotherapy department of the
      University Hospital of Leuven, the mean ratio of the measured entrance dose (TLD)
      to the entrance dose calculated by the TPS, is equal to 0.986+/-0.017 (1SD)
      (N=8), after correction of an error detected in one of the patient treatments.
      For the 18 radiotherapy centres participating in the mailed in vivo TLD study,
      the mean measured versus stated entrance dose for patients treated in a (60)Co
      and 6 MV photon beam is 1.004+/-0.021 (1SD) (N=143). CONCLUSIONS: From the
      results, it can be deduced that the build-up caps and the proposed calibration
      methodology allow the use of TLD in the form of powder to be applied in large
      scale in vivo dose audits.

PMID- 15465152
TI  - Overview of radiotherapy resources in Latin America: a survey by the
      International Atomic Energy Agency (IAEA).
AB  - BACKGROUND AND PURPOSE: An analysis of the resources for radiotherapy in Latin
      America was done to establish a baseline to help plan future development in the
      region. PATIENTS AND METHODS: The data from 19 countries were obtained during
      three International Atomic Energy Agency (IAEA) regional meetings. The survey
      covered radiotherapy centres, major equipment and personnel. The centres were
      categorised into four different levels. Data were related to economic and
      population indices. RESULTS: Four hundred and seventy centres were identified in
      18 countries. Centres were divided into 4 levels: half were included in level 1,
      25% in level 2 and 18% in level 0 (stand alone teletherapy machines). Human
      resource represents 933 radiation oncologists, 357 physicists and 2326 radiation
      therapy technologists. In general, availability of equipment and personnel was
      related to economic status of the country. CONCLUSIONS: Although there is a
      shortfall of equipment, the major restriction to patient service is an
      insufficient number of specialists in 16 of the 18 countries. An upgrade of
      standards in many centres is required to offer a comprehensive radiation oncology
      service. The information provided in this paper represents a useful base to plan
      future development in terms of equipment installation and training programs.

PMID- 15465153
TI  - Stable overall referral rates of primary radiotherapy for newly diagnosed cancer
      patients in the ageing population of South-Eastern Netherlands, 1975-1998.
AB  - BACKGROUND AND PURPOSE: To determine the primary radiotherapy (RT) consumption in
      a population of almost one million inhabitants, served by one RT centre. Primary
      RT was defined as being planned, started or finished within 4-6 months of
      diagnosis. Application was evaluated according to tumour category, stage and year
      of diagnosis during three 8-year periods: 1975-1982, 1983 -1990 and 1991-1998.
      RESULTS: Most patients were between 60 and 75 years. The number of patients
      receiving primary RT increased with 3% annually over the whole studied period,
      but remained proportionally stable for males at 30% and decreased for females
      from 36.2 to 34.6%. A decrease of referral rates for patients with gynaecological
      cancer was observed. The introduction of breast-conserving therapy in 1981 and of
      population screening for women aged 50-69 years in 1992 led to a considerable
      increase of primary RT. The eightfold increase in number of irradiated patients
      with localised prostate cancer rather reflected a higher detection rate than an
      increased referral rate. Except for an important increase of irradiated patients
      with rectal cancer, largely due to the shift to preoperative RT since 1994, and
      of patients with brain cancer, only slight alterations in referral rates were
      observed for the other cancers. CONCLUSIONS: Use of primary RT remained
      proportionally steady and modest. The marked increase in workload was mainly due
      to more and earlier detection of breast and prostate cancer and treatment changes
      in rectal cancer. Decreases were observed for each of the gynecological cancers.

PMID- 15465155
TI  - Comment on: 'Serious adverse effects of amifostine during radiotherapy in head
      and neck cancer patients' Radiother Oncol 70: 261-264, 2004 by Dr Rades et al.

PMID- 15465156
TI  - Bilateral leg amputation following chemoradiation for squamous carcinoma of the
      anus.

PMID- 15465157
TI  - [Epidemiology and prognostic significance of bladder sphincter disorders after an
      initial cerebral hemisphere vascular accident].
AB  - OBJECTIVE: To document incidence of poststroke urinary incontinence and retention
      and to determine its effect on 3 months outcome. METHODS: Prospective cohort
      study. One hundred fifty-five cases of first hemispherical stroke were classified
      by continence status, retention or incontinence, at D2 after stroke. Age, sex,
      stroke location and aetiology, hypertension, diabetes were noted. Outcome data
      collected at D15 and D90 included impairments, disabilities, quality of life and
      case fatality rates. Disabilities were measured with Barthel Index (BI), Franchay
      Arm Test (FAT), New Functional Ambulation Classification (NFAC) and quality of
      life with EuroQol. RESULTS: Of the 155 patients, 62 had initial urinary
      disorders. The incidence was 40% at D2, 32% at D15 and 19% at D90. Retention
      represented 36% of urinary disorders at D2 and D15 and only 19% at D90. Urinary
      disorders were associated with motor weakness, lower Barthel Index, dysphasia,
      aphasia, apraxia and unilateral neglect. There was no relation with sex, age,
      stroke aetiology and diabetes. At D90, patients with initial urinary disorders
      had higher case fatality rates 22% versus 16% (P < 0.0001) and greater
      disabilities: BI of 60 versus 90 (P < 0.0001), NFAC of five versus seven (P <
      0.0001), FAT of four versus six (P = 0.0019). CONCLUSION: Poststroke urinary
      disorders were associated with stroke gravity and adversely affected D90 stroke
      survival rates and functional outcome. Retention was strongly associated with D90
      survival rates.

PMID- 15465158
TI  - [Validation of the motor capacities scale: a specific evaluation of manual
      abilities in tetraplegics who undergo functional surgery of the upper limbs].
AB  - OBJECTIVE: Metrological investigation to develop a motor capacities scale (MCS)
      specifically designed for tetraplegics who undergo a functional surgery of upper
      limbs. METHODS: From diverse sources-review of literature, discussion with
      patients and therapists-, 328 daily life activities were compiled. Eighty of them
      were identified as motor capacities and correspond to basic and functional tasks
      performed by tetraplegics independently of contextual and environmental factors.
      Because of the absence of a reference test, a process of validation was required.
      In the preliminary study, patients and occupational therapists were asked to
      criticize the pertinence of the study. In the pilot study, patients were assessed
      on the basis of a protocol. Feasibility of the evaluation was also studied. The
      intermediate study was focused on the interrater reproducibility. The prefinal
      study aimed at assessing construct validity. In the final study, the external
      structure of the scale and responsiveness to change provided by functional
      surgery were analyzed. RESULTS: The preliminary and pilot studies revealed the
      good acceptability of the scale by both the patients and the therapists. Face and
      content validity were enhanced by the multidisciplinary and multicenter approach.
      Global reproducibility was found to be excellent (intraclass correlation
      coefficient = 0.99). MCS was correlated with the Sollerman test, the functional
      independence measure (FIM), the ASIA motor score, dynamometric scores of Jamar
      and Preston. No correlation was found with the interval since the onset of the
      tetraplegia, the educational level and the age at the time of the evaluation. A
      factorial analysis was performed in 125 patients (146 observations) and revealed
      one main dimension that appears to reflect manual abilities. Responsiveness to
      change was important regarding the short time following surgery. The final
      version of the MCS comprises 31 items classified in six functional categories:
      transfers, positioning on a Bobath's couch, positioning in a wheelchair,
      locomotion, motor capacities of spatial exploration and motor capacities for
      grasping and gripping. CONCLUSION: The MCS displays satisfactory metrological
      properties: a good apparent and content validity, an excellent reproducibility
      and a good construct validity. The data showed that sensitivity to change was
      good enough to consider the MCS as a valid means of assessment of the
      effectiveness of upper limb functional surgery in tetraplegics.

PMID- 15465159
TI  - [The Dijon Physical Activity Score: reproducibility and correlation with exercise
      testing in healthy elderly subjects].
AB  - PURPOSE: To validate a French physical activity score for current use in healthy
      elderly people. PATIENTS AND METHODS: A brief questionnaire was developed for
      healthy elderly subjects older than 72 years. Questions asked about self-assessed
      physical fitness (1), daily activity (2), leisure and sport activity (5) and rest
      time (1). Correlations were searched between the score and several parameters of
      physical fitness: maximal exercise stress test (peak VO(2)), six-minute walk
      test, 200-meter long walk test, timed up an go test. RESULTS: A total of 57
      subjects were studied (mean age, 77.6 +/-3.6 years; 28 females and 29 males). The
      mean time to complete the questionnaire was 3.96 minutes. Reproducibility was
      0.606, as determined by Spearman's coefficient. Correlations were found between
      the physical activity score and peak VO(2) (0.302, P <0.05) and peak power
      (0.257, P <0.10). CONCLUSIONS: This easily obtained physical activity score
      provides a new way to assess physical activity in active elderly subjects. The
      physical score correlated in part with maximal ability but must be validated in
      several diseases.

PMID- 15465160
TI  - [Treatment of focal upper limb spasticity with botulinum toxin after stroke.
      Interest of an individual approach].
AB  - INTRODUCTION: It is now demonstrated that botulinum toxin can improve upper limb
      spasticity after stroke. OBJECTIVES: This study was designed to assess the
      efficacy of botulinum toxin on upper limb spasticity with an individual approach.
      METHODS: Prospective study on 18 patients who had disabling spasticity of upper
      limb after stroke. For each patient, the treatment's target was fixed preliminary
      to botulinum toxin injection. Evaluation of efficacy (Ashworth scale and
      predefined targets) was performed at 1 month and treatment continuation was
      decided individually. RESULTS: A beneficial effect was reported by most patients
      when the treatment was aimed at improving comfort or quality of life. In one
      case, the treatment was designed to improve grasping. In that case, no effect was
      reported. For three patients, a neurotomy was performed in order to obtain a long
      lasting effect. For nine patients, repeated injections were decided. For the six
      other patients, no long-standing treatment was performed. DISCUSSION: This study
      confirms that botulinum toxin can improve comfort of patients with upper limb
      spasticity. On the base of our experience, we discussed contribution of botulinum
      toxin to enhance and optimise strategies for the treatment of focal upper limb
      spasticity with emphasis on the comparison with selective neurotomy.

PMID- 15465161
TI  - [Prospective study of the outcome at one year of patients with chronic low back
      pain in a program of intensive functional restoration and ergonomic intervention.
      Factors predicting their return to work].
AB  - OBJECTIVES: Evaluation of 1-year outcome after patients with chronic low back
      pain participated in an intensive functional restoration program associated with
      an ergonomic intervention on the workplace. Study of the factors predicts a
      return to work. METHODS: Prospective study of a cohort of 87 patients face major
      difficulties due to low back pain at work. Patients who visited a
      multidisciplinary clinic were included. Parameters, evaluating physical and
      psychological status, quality of life, presence at work, length of sick leaves,
      were determined before and after the program and at 6 and 12 months' followup.
      The correlation between these parameters and presence at work at 1 year was
      studied. RESULTS: A total of 86 patients completed the program; three were lost
      to followup at 1 year. Ergonomic interventions were tried in 53 patients. All
      parameters were improved at the end of the program and remained significantly
      improved at 12 months. A total of 90% of the patients returned to work at the end
      of the program, whereas only 17% were at work before; 72% were at work in 1 year.
      The number of sick leave days decreased by 60%. The Dallas index at the beginning
      and the end of the program, the number of sick leave days before the program and
      score on the item "feels able to work" correlated with the presence at work in 1
      year. There was no correlation between presence at work and physical parameters.
      CONCLUSION: This study shows the effect of the program and determines factors
      predictive of successful return to work for patients with chronic low back pain.
      Further data are necessary to discuss the specific effect of ergonomic
      interventions.

PMID- 15465162
TI  - [Should companies employees, managers and doctors be associated in functional
      back pain restoration programs?].

PMID- 15465163
TI  - [Pharmacology and upper limb poststroke spasticity: a review. International
      Society of Prosthetics and Orthotics].
AB  - OBJECTIVES: The present study, conducted for the consensus conference "Orthotic
      management of stroke patients", organized by the International Society of
      Prosthetics and Orthotics, on September 2003, reviews the pharmacological,
      general, or local treatments available for post-stroke upper-limb spasticity.
      METHOD: A search of the international literature in the Medline and the Reedoc
      data banks for papers related to post-stroke upper-limb spasticity. Each paper
      was given a rating of A, B, or C (in term of quality) according to the
      instructions of the organization committee. RESULTS: General pharmacological
      treatments such as use of baclofen, tizanidine and dantrolene, regional
      treatments such as intrathecal baclofen, and local treatments with use of
      chemical neurolysis and alcohol or phenol are recommended for conditions
      described in papers with a grade of B. Neuromuscular blockade with botulinum
      toxin is recommended for conditions described in papers with a grade of A.
      DISCUSSION/CONCLUSION: Despite a satisfactory grade of recommendation, general
      pharmacological treatments are limited by adverse events and lack of evidence of
      functional benefit. Intrathecal baclofen should be discussed for upper-limb
      spasticity, but further studies are needed before its use can be recommended. The
      place of chemical neurolysis with use of alcohol or phenol should be evaluated
      with surgical neurotomy and botulinum toxin therapy. The use of botulinum toxin
      is the only treatment supported by scientific results, but many questions remain
      about the site of injection, how to improve efficacy and influence on
      neurological recovery.

PMID- 15465164
TI  - How do nursing students regard their future career? Career preferences in the
      post-modern society.
AB  - This article presents findings from a study of 301 Norwegian nursing students'
      opinions of their future career. The initial survey took place 7 months after the
      commencement of nursing training in 1998/99 with a follow-up after 2 1/2 years.
      Data was collated using a questionnaire with closed questions and supplemented by
      semi-structured in-depth, audio taped interviews concerning the students'
      professional socialisation. The findings from the initial survey indicate that
      motives like human contact, helping others and job security (i.e. low risk of
      being laid off) were important. Plans for further education after finishing the
      bachelor programme in nursing were abundant. Analysis of the second data-set will
      show whether there is a change in the students' plans for their future education
      and career. For nearly 80% of the students it was very important that the
      bachelor degree could serve as a basis for further education. Multiple regression
      analysis showed that nursing students who emphasise this importance are less
      interested in giving care and help to others, and this attitude is confirmed in
      the interviews. Career preferences were often midwifery, public health or
      practice in high tech areas like anaesthetics, and not care for chronically ill
      or elderly patients; areas where there is a shortage of nurses.

PMID- 15465165
TI  - Irish nursing students' changing levels of assertiveness during their pre
      registration programme.
AB  - BACKGROUND: Stress and bullying have been found to be common problems in a number
      of studies of Irish nursing and midwifery. Victims of bullying need high levels
      of assertiveness to enable them to withstand the stress of victimization. It was
      deemed important to measure nursing students' level of assertiveness prior to,
      and near completion of, their pre-registration education programme. Aim. To
      ascertain nursing students' perceived levels of assertiveness prior to, and
      nearing the completion of, their three-year pre-registration programme. METHODS:
      Ethical approval was given. The students commencing general nurse education
      programmes in two schools in Southern Ireland agreed to take part (n=72). A
      questionnaire adapted from a number of assertiveness scales, and tested for
      validity and reliability in this population, was used to collect data. RESULTS:
      In general, students' reported assertiveness levels rose as they approached
      completion of their three-year education programme. DISCUSSION: The resource
      constrained health service of the 21st century requires nurses who are assertive
      to meet the needs of its users. Nursing students' assertiveness skills could be
      augmented through concentrated efforts from nurse educationalists and clinicians
      to reduce the communication theory practice gap in nurse education today. To
      address the multi-dimensional nature of assertiveness, strategies to increase
      assertiveness should operate at the individual, interface and organisational
      level. CONCLUSIONS: The students in this study reported an increase in levels of
      assertiveness as they approached completion of their three-year education
      programme. To function as effective, safe practitioners registered nurses need to
      be assertive, therefore education in assertiveness should be an integral part of
      their preparation. The precise composition and mode of delivery of this education
      requires exploration and evaluation.

PMID- 15465166
TI  - Keeping afloat: student nurses' experiences following assignment referral.
AB  - The retention of nursing students is an ongoing problem, both within the United
      Kingdom (UK) and internationally. While there is a plethora of literature
      relating to student attrition, there is an absence of evidence in relation to the
      experiences of those students who are struggling to meet the demands of nursing
      programmes. Using an inductive sociological enquiry based approach, this study
      sought to examine the experiences of student nurses after referral on the first
      attempt of a summative assessment. Nursing students who had failed an assignment
      (n=20) were invited to participate. Data was collected using focus groups, with
      the emergent themes collapsed into a concise format using thematic content
      analysis. Four key themes were identified: desire to succeed; acceptance of
      personal failure; recognition of personal attributes required for success; and
      responsibility for personal success and failure. Students remained on the
      programme, despite struggling with financial and personal difficulties, because
      the desire to become a qualified nurse outweighed transient hardships. This paper
      will illustrate the benefits of understanding the students' experiences, in order
      to ensure the support students receive is appropriate to their needs.
      Understanding the support strategies as perceived by the students may prevent
      further wastage from nursing programmes.

PMID- 15465167
TI  - Children's perceptions of the nursing profession in Poland.
AB  - The drawing, as a kind of artistic language, used by the child-artist to express
      his or her thoughts and opinions concerning their environment is an immensely
      interesting form of cognition for the viewers of such artistic creations. The aim
      of the study was the analysis of the presentation of the image of the nursing
      profession created by children and the application of these experiences in
      vocational education of nurses. The objects of the analysis, were 182 artistic
      creations of children living in eastern Poland. The detailed analysis of the
      works was carried out by three independent competent judges who grouped the works
      according to the accepted indicators of evaluation. The young artists created the
      image of the nurse that presents a detailed range of professional duties, the
      quality of the child-nurse relationship and the prognostic vision of the new
      activities that will be put into practice in the future. The rich content of the
      drawings was complemented by the high artistic value of the composition. The
      study material collected should be used not only by nurses participating in care
      of children, but also in vocational education of nurses for more complete
      preparation of candidates to perform their future profession.

PMID- 15465168
TI  - Learning from the experience of working with consumers in educational
      developments.
AB  - AIM: The aim of this paper is to report the experience of working with local
      parents as collaborators in an educationally focussed research study. This work
      subsequently led to the development of a new module aimed at professionals
      providing parenting support. The ensuing discussion centres on the involvement of
      healthcare consumers in the development of educational programmes. METHODS: Focus
      group interviews were held with local parents to identify their various
      experiences of parenting support services. In addition the interviews were used
      as a means of recruiting local parent volunteers willing to join the research
      advisory group. This group had the task of guiding both the research and
      development of the educational programme. FINDINGS: Involvement of the parents
      introduced fresh insights to both the understanding of the content of parent
      education module and the necessary ingredients needed for effective consumer
      involvement. CONCLUSION: Lecturers have gained first hand experience of working
      collaboratively with parents in carrying out a research study and curriculum
      development. Three key issues emerged from this experience. These included the
      identification of who the consumer is, the approaches and skills required by
      professionals and lastly the importance of resources to support this commitment.

PMID- 15465169
TI  - The development of moral judgment during nursing education in Finland.
AB  - This study describes moral judgment among first- and last-year nursing students
      in Finland and examines the effects of ethics teaching on the development of
      moral judgment. The data for this quantitative cross-sectional study were
      collected using the Defining Issues Test (DIT), which is based on Kohlberg's
      theory of moral reasoning stages. The questionnaires were sent to four
      polytechnics, which offer nursing education in southern Finland. A total of 52
      first-year students and 54 last-year students participated. The results showed
      that students who had had to deal with ethical dilemmas in their practical
      training had higher moral judgment than students who did not. Last-year students
      had higher moral judgment than first-year students. Last-year students resorted
      to principle-based thinking more often than first-year students in resolving DIT
      dilemmas. The differences between the two groups were statistically significant.
      The results indicate that nursing education may has an effect upon students'
      moral judgment.

PMID- 15465170
TI  - Information technology in health professional education: why IT matters.
AB  - This paper analyses the potential of information technology (IT) to transform the
      process of learning in higher education, particularly health professional
      education. It is argued that IT, although very much part of the infrastructure of
      the modern university has yet to make its full impact on teaching and learning
      processes. The expectations of students and demands for improved flexibility and
      access make it inevitable that IT will become an integral part of teaching and
      learning despite inherent resistance to change. The potential benefits of IT are
      identified as: transmission of high quality content, support of life-long
      learning, flexibility of access and enhanced opportunities for communication.
      These concepts are explored in the context of health professional education. It
      is argued that universities cannot survive without harnessing the power of IT to
      improve the educational experience of students but lecturers should ensure that
      this is underpinned by sound educational theory.

PMID- 15465171
TI  - Nursing doctoral education in Turkey.
AB  - Quality health care is an issue of concern worldwide, and nursing can and must
      play a major and global role in transforming the healthcare environment.
      Doctorally prepared nurses are very much needed in the discipline to further
      develop and expand the science, as well as to prepare its future educators,
      scholars, leaders, and policy makers. In 1968, the Master of Science in Nursing
      Program was initiated in Turkey, followed by the Nursing Doctoral Education
      Program in 1972. Six University Schools of Nursing provide nursing doctoral
      education. By the graduating year of 2001, 154 students had graduated with the
      Doctor of Philosophy in Nursing (Ph.D.), and 206 students were enrolled in
      related courses. Many countries in the world are systematically building various
      collaborative models in their nursing doctoral education programs. Turkey would
      like to play an active role in creating collaborative nursing doctoral education
      programs with other countries. This paper centres on the structure and model of
      doctoral education for nurses in Turkey. It touches on doctoral programs around
      the world; describes in detail nursing doctoral education in Turkey, including
      its program structure, admission process, course units, assessment strategies and
      dissertation procedure; and discusses efforts to promote Turkey as a potential
      partner in international initiatives to improve nursing doctoral education.

PMID- 15465172
TI  - Moving from novice to expert - the value of learning in clinical practice: a
      literature review.
AB  - The Fitness for Practice Report (UKCC 1999) acknowledged the importance of
      competent nursing practice and shared the responsibility for achieving this by
      making United Kingdom National Health Service employees jointly responsible for
      this with higher education teachers. This article presents a wide review of
      educational literature, to discover how both the constructivist and the
      sociocultural approach to learning will promote nursing expertise. Consideration
      of both these approaches to learning is germane to pre and post registration
      nursing courses, given that learning is both culturally situated and individually
      constructed from a variety of different sources, and the review demonstrates the
      pivotal position of the mentor and other practice teachers.

PMID- 15465173
TI  - Contributing to the theory development of preceptorship.
AB  - The purpose of the study was to clarify and analyze the concept of preceptorship
      as experienced by the preceptor. Preceptorship is a teaching method commonly used
      in many professions. The current study assists in the clarification and analysis
      of the concept of preceptorship as experienced by the preceptor. Regarding
      methodology, the literature was reviewed to compare the experience of clinical
      teaching with preceptorship. Literature was reviewed from the following
      fields/domains: nursing, medicine, education, social work, rehabilitation,
      dentistry, law, and pharmacy. Through application of the framework outlined by
      Walker, L.O., Avant, K.C., 1995. Strategies for Theory Construction in Nursing,
      third ed. Appleton & Lange, Norwalk, attributes, antecedents, consequences, and
      empirical referents were identified that help define preceptorship. There were
      three main findings: The nature of the relationship between the preceptor and
      preceptee is pivotal, evaluation is a challenge, and preceptorship is distinct
      from mentorship. The consequences of a preceptorship experience are better
      prepared and more confident preceptors, evolution into a mentorship relationship,
      and professional development of both the preceptor and the preceptee. This
      article concludes with numerous topics that could be addressed in future
      research: (a) screening tools for the preceptor; (b) evaluation of the preceptee;
      (c) the relationship between preceptee, preceptor, and faculty; (d) preparation
      of the preceptor, and (e) rewarding the preceptor.

PMID- 15465174
TI  - An evaluation of an educational programme to prepare family health nurses.
AB  - In 1998 the World Health Organisation (WHO) Europe proposed a new type of
      community based nurse called the family health nurse (FHN). Although it was
      initially envisaged that 18 European countries would take part in the development
      of the FHN role through parallel processes of education and implementation,
      Scotland has been significantly ahead of other countries in enacting this plan. A
      pilot project involving community nurses from four remote and rural regions of
      Scotland was conducted between 2001 and 2003. A Scottish University was
      commissioned to provide a degree-level course for registered nurses with a
      minimum of two years post-registration qualifying experience. This paper
      summarises the main findings and issues arising from an external research
      evaluation of this educational programme. The programme was found to differ
      substantially in focus and format from other specialist community nursing
      programmes available in Scotland. Moreover there were key differences from the
      curriculum proposed by WHO Europe, in that there was more grounding in North
      American family nursing models and less focus on management and leadership. This
      customized degree programme provides a precedent for other educational providers
      in the UK to reconsider their approach to specialist practice degree level
      education.

PMID- 15465175
TI  - Investigation of dissolved uranium content in the watershed of Seine River
      (France).
AB  - A systematic survey of dissolved uranium activity was carried out in the Seine
      and the Marne over one year. A small watershed, the Grand Morin, included in the
      Seine one, was also investigated from stream to medium-sized rivers. The
      Melarchez stream exhibits low but variable dissolved 238U levels (3.3 +/- 2.0 mBq
      l(-1)). Thereafter, uranium activities show a rapid increase to reach, from the
      Grand Morin River, a rather constant range (8-11 mBq l(-1)). On the Marne before
      the confluence with the Seine, dissolved 238U is nearly invariable (9.1 +/- 0.8
      mBq l(-1)), for flow rates comprised between 60 and 423 m3 s(-1). Dissolved 238U
      in the Seine corresponds to almost triple the global mean riverine uranium
      concentration. In the estuary of the Seine, uranium shows a gradual increase,
      resulting from conservative mixing of river with sea waters.

PMID- 15465176
TI  - Radioactivity of the soil in Vojvodina (northern province of Serbia and
      Montenegro).
AB  - The widespread public belief that during the bombardment of Vojvodina
      (Yugoslavia) this region was contaminated by depleted uranium has recently raised
      public concern with respect to the potential contamination of agricultural
      products due to soil radioactivity. Based on the gamma-spectrometric analysis of
      50 soil samples taken from the region of Vojvodina we concluded that there is no
      increase of radioactivity that could endanger the food production. Taking into
      account the transfer factors of 137Cs to plants, the measured activity
      concentrations of this isotope should not endanger the health safety of the
      produced food. No traces of depleted uranium have been found. The natural
      radioactivity levels are compared with the results form other countries.

PMID- 15465177
TI  - Seasonal variation of the radiocaesium transfer soil-to-Swiss chard (Beta
      vulgaris var. cicla L.) in allophanic soils from the Lake Region, Chile.
AB  - The transfer factor (TF) of radiocaesium from soil-to-Swiss chard (Beta vulgaris
      var. cicla L.) was studied in two different characteristic allophanic soils
      (umbric andosol and dystric fluvisol) of the Lake Region, an important
      agricultural region situated in central-south Chile. To investigate especially
      the time dependence and the effect of K-fertilisation on the TF, field
      experiments were conducted. Plots of 7.6 m2 were labelled with 100 kBq 134Cs m(
      2) at Santa Rosa Experiment Station close to the city of Valdivia characterised
      by a temperate climate and high precipitation rates. The variation in time of the
      radiocaesium TF soil-to-Swiss chard was observed during two consecutive years
      after soil contamination by sequential harvests and radiocaesium analyses of the
      plants. The TFs showed no significant ageing effect, but a pronounced seasonal
      decrease with effective half-lives of about 140 and 160 days for the umbric
      andosol without and with K-fertilisation, respectively, and of 50 and 60 days for
      the dystric fluvisol without and with K-fertilisation, respectively. The effect
      of K-fertilisation on the absolute values of the TF was determined by the ratio
      between the median TF values obtained for corresponding dates without and with
      use of K-fertiliser. A ratio of TF(without K)/TF(with K) = 1.8 for the umbric
      andosol and TF(without K)/TF(with K) = 2.9 for the dystric fluvisol was obtained,
      indicating a reduction of the TF by applying 90 kg K ha(-1). The maximal values
      of the TF to chard predicted by the equation characterising the seasonal decrease
      of the TF at the beginning of the harvest periods are 0.19 for the umbric andosol
      and 0.11 for the dystric fluvisol, both values for soil treated with common K
      fertilisation.

PMID- 15465178
TI  - Plant uptake and downward migration of 85Sr and 137Cs after their deposition on
      to flooded rice fields: lysimeter experiments with and without the addition of
      KCl and lime.
AB  - In order to study the plant uptake and downward migration of radiostrontium and
      radiocesium deposited on to a flooded rice field, 85Sr and 137Cs were applied to
      the standing water over an acidic sandy soil in planted lysimeters. The plant
      uptake was quantified with the areal transfer factor (TFa, m2 kg(-1)-dry plant).
      Following the spiking 14 days after transplanting, the TFa values for the hulled
      seeds were 3.9 x 10(-4) for 85Sr and 1.4 x 10(-4) for 137Cs, whereas those for
      the straws were 1.3 x 10(-2) and 3.2 x 10(-4), respectively. The 137Cs TFa from
      the spiking at the anthesis/milky-ripe stage was several times higher than that
      from the earlier spiking, whereas the difference was much less in the 85Sr TFa.
      Such an increase in the 137Cs TFa was attributed mainly to an enhanced plant-base
      uptake. The addition of KCl and lime after the spiking significantly reduced the
      TFa values of both radionuclides. The reducing effect was greater for the later
      spiking. An appreciable fraction of the applied activity leached out of the
      lysimeter for 85Sr, whereas a negligible fraction leached for 137Cs. The leaching
      was remarkably increased by the KCl and lime addition for both. A conspicuous
      localization of 137Cs with respect to the soil surface was observed. In a batch
      experiment, the 137Cs concentration in the standing water decreased more rapidly
      than that of 85Sr, both of which were fitted to the power functions of the
      elapsed time. To add KCl and lime slowed such decreases to lessen the
      distribution coefficients (Kd) of both 85Sr and 137Cs.

PMID- 15465179
TI  - Uptake and depuration of 131I by the edible periwinkle Littorina littorea: uptake
      from seawater.
AB  - Uptake and depuration experiments for the edible periwinkle Littorina littorea
      have been performed using 131I-labelled seawater. Throughout the experimental
      phase the winkles were fed on unlabelled Chondrus crispus. 131I concentrations in
      winkles during uptake followed linear first-order kinetics with an uptake half
      time of 11 days, whereas for depuration a triphasic sequence with biological half
      lives of 4, 23 and 56 days was determined. In general, iodine turnover in winkles
      via labelled seawater appears to be slower than observed for other molluscs (2-3
      days). Most of the activity prior to and after depuration is found to be in the
      shell, with indications that shell and soft parts accumulate and depurate 131I at
      a similar rate. The operculum displays the highest specific activity of all
      fractions with a concentration factor of 750 l kg(-1). Concentration factors for
      whole winkle, shell, soft parts and digestive gland are in the order of 40-60 l
      kg(-1), higher than the IAEA recommended CF value for iodine in molluscs of 10 l
      kg(-1). The 131I CF in winkles is closer to that of the conservative
      radionuclides 99Tc and 137Cs than the CF of the particle reactive radionuclides
      (239,240)Pu and 241Am.

PMID- 15465180
TI  - Application of activated charcoal radon collectors in high humidity environments.
AB  - Most commercially based activated charcoal radon collectors were designed for use
      in indoor environments. However, at present, they are often used for research in
      radon surveys in unique environments, such as in the bathrooms, underground
      areas, mines, caves and tunnels. In these environments, the relative humidity
      would be around 100%, and a change in the sensitivity of cpm(Bq m(-3))(-1)(radon)
      would occur. For this study, the reduction in the sensitivity of activated
      charcoal radon collector due to environmental humidity was investigated, and the
      data correction was discussed. Here, ST-100 (Pico-Rad) was selected as an example
      of a familiar activated charcoal radon collector. According to our performance
      test, the humidity of 90% (20 degrees C) resulted in a 15% reduction of the
      sensitivity for 24 h collection. The ST-100 user should discuss the necessity of
      data correction by comparing the change of sensitivity with other levels of
      estimation errors.

PMID- 15465181
TI  - Role of the fungal mycelium in the retention of radiocaesium in forest soils.
AB  - The aim of this work was to study possible binding of 137Cs to various organic
      components in the soil and fungi, by using various sequential extraction
      procedures. The retention and binding of 137Cs has been studied in two horizons
      Of/Oh and Ah/B of a Ukrainian forest soil. The exchangeable fractions 137Cs from
      soil (sum of H2O and 1 M NH4OAc fraction) were found to be 12% in the organic
      rich layer (range 11-14%) and 23% in the organic-poor (range 20-29%). The
      hydrolysis with 10% H2SO4 resulted in an additional release of 30% of 137Cs from
      the organic-rich soil (range 30-35%) and 38% from the organic-poor soil horizon
      (range 27-53%). Extraction with 30% H2O2 released 11 and 15% of the 137Cs
      activity from organic-rich and organic-poor soil horizons. The corresponding
      values for treatment with 98.8% NaOCl were about 27% in both types of soil. About
      11% of the total 137Cs activity was found in the humic acid fraction, about 5% in
      the fulvic fraction and 46% in the residue fraction. Relatively high level of
      137Cs activity in soil (ca. 50%) was thus still left unsolved in the residue
      fraction. About 29% of 137Cs activity concentration in fungal mycelia was found
      as water soluble with a range of 11 to 41%. Additionally 24% of the 137Cs
      activity from mycelia was released by 1 M ammonium acetate extraction. Together,
      water and 1 M ammonium acetate extraction released about 53% of the total 137Cs
      activity in the mycelia. In fruit bodies of mycorrhizal fungi, 68% of the total
      137Cs inventory was found to be water soluble at room temperature and 93% at 80
      degrees C.

PMID- 15465182
TI  - 40K, 137Cs, 90Sr, 238,239+240Pu and 241Am in mammals' skulls from owls' pellets
      and owl skeletons in Poland.
AB  - Skulls of small mammals belonging to two species of rodents and three species of
      insectivores collected in Eastern Poland were the subject of the present
      investigation. The skulls were separated from owl pellets. Activities of 40K,
      137Cs, 90Sr, 238,239+240Pu and 241Am were determined by means of gamma
      spectrometry as well as liquid scintillation spectrometry or alpha spectrometry
      along with relevant radiochemical procedures. A detailed description of the
      procedures is provided. The research was supplied with the analysis of three
      skeletons of owls. No measurable difference between the skulls of rodents and
      insectivorous animals with regard to activity of any of the examined
      radionuclides was found. No accumulation effect in the owl skeletons was
      detected. Though measured activities of 137Cs and 40K for the skulls were of the
      same magnitude as those found previously for large wild herbivorous animals from
      typical locations in Poland, those for 90Sr were even lower than previously
      determined. A big difference was found for activities of plutonium and americium
      isotopes. Their mean activities were higher by an order of magnitude when
      compared to the examined previously values. The maximum 239+240Pu activity was
      equal to 97.5+/-7.7 mBq/kg, with 65% of it originating from global fallout.
      Relatively high content of transuranic elements found for rodents and
      insectivorous mammals seems to be unrelated to their feeding habits and should
      rather be attributed to the living conditions. It is suggested that small
      mammals, together with tiny soil particles present in mid-soil living tunnels,
      can inhale the transuranic elements.

PMID- 15465183
TI  - Natural activities of 40K, 238U and 232Th in elephant grass (Pennisetum
      purpureum) in Ibadan metropolis, Nigeria.
AB  - Samples of elephant grass collected at some pasturing farmlands across different
      locations in Ibadan metropolis were analyzed for their natural radioactivity
      concentrations due to 40K, 238U and 232Th radionuclides. Radioactivity
      measurements were carried out using gamma-ray spectroscopy. The average
      radioactivity concentration of 40K was found to be 25.7+/-5.5 Bq kg(-1) for 238U
      and 33.4+/-3.9 Bq kg(-1) for 232Th. The radiological health implication to the
      population that may result from these values is found to be very low and almost
      insignificant. No artificial radionuclide, however, was detected in any of the
      samples, hence, measurements have been taken as representing baseline values of
      these radionuclides in the grass in the metropolis.

PMID- 15465184
TI  - An overview of an indoor radon study carried out in dwellings in India and
      Bangladesh during the last decade using solid state nuclear track detectors.
AB  - This paper reports on radon concentrations in dwellings from fifty different
      locations of India. The incorporated data were obtained using the passive solid
      state nuclear track detector technique. The estimated geometric mean value for
      India is 67.1 Bq m(-3). Chuadanga in Bangladesh had the lowest observed indoor
      radon concentration of 27.3 Bq m(-3) and Una in the northern part of India had
      the highest concentration of 281.5 Bq m(-3). This paper discusses the national
      geometrical mean value in terms of the national geometric mean values of other
      countries and also in terms of the geological influence. The estimated indoor
      radon levels are compared with the indoor radon levels as recommended by the
      International Commission on Radiation Protection (ICRP). It was observed that
      there are several locations in India where dwellings have higher indoor radon
      levels than the ICRP recommended value and requires some sort of intervention
      from regulating authorities. The mean value for indoor radon level given in the
      report of UNSCEAR 2000 for India needs to be revised.

PMID- 15465185
TI  - ASTRO's core physics curriculum for radiation oncology residents.
AB  - In 2002, the Radiation Physics Committee of the American Society of Therapeutic
      Radiology and Oncology (ASTRO) appointed an Ad-hoc Committee on Physics Teaching
      to Medical Residents. The main initiative of the committee was to develop a core
      curriculum for physics education. Prior publications that have analyzed physics
      teaching have pointed to wide discrepancies among teaching programs. The
      committee was composed of physicists or physicians from various residency program
      based institutions. Simultaneously, members had associations with the American
      Association of Physicists in Medicine (AAPM), ASTRO, Association of Residents in
      Radiation Oncology (ARRO), American Board of Radiology (ABR), and the American
      College of Radiology (ACR). The latter two organizations' representatives were on
      the physics examination committees, as one of the main agendas was to provide a
      feedback loop between the examining organizations and ASTRO. The document
      resulted in a recommended 54-h course. Some of the subjects were based on
      American College of Graduate Medical Education (ACGME) requirements (particles,
      hyperthermia), whereas the majority of the subjects along with the appropriated
      hours per subject were devised and agreed upon by the committee. For each subject
      there are learning objectives and for each hour there is a detailed outline of
      material to be covered. Some of the required subjects/h are being taught in most
      institutions (i.e., Radiation Measurement and Calibration for 4 h), whereas some
      may be new subjects (4 h of Imaging for Radiation Oncology). The curriculum was
      completed and approved by the ASTRO Board in late 2003 and is slated for
      dissemination to the community in 2004. It is our hope that teaching physicists
      will adopt the recommended curriculum for their classes, and simultaneously that
      the ABR for its written physics examination and the ACR for its training
      examination will use the recommended curriculum as the basis for subject matter
      and depth of understanding. To ensure that the subject matter and emphasis remain
      current and relevant, the curriculum will be updated every 2 years.

PMID- 15465186
TI  - Results of a survey regarding irradiation of internal mammary chain in patients
      with breast cancer: practice is culture driven rather than evidence based.
AB  - PURPOSE: To examine the self-reported practice patterns of radiation oncologists
      in North America and Europe regarding radiotherapy to the internal mammary lymph
      node chain (IMC) in breast cancer patients. METHODS AND MATERIALS: A survey
      questionnaire was sent in 2001 to physician members of the American Society for
      Therapeutic Radiology and Oncology and European Society for Therapeutic Radiology
      and Oncology regarding their management of breast cancer. Respondents were asked
      whether they would treat the IMC in several clinical scenarios. RESULTS: A total
      of 435 responses were obtained from European and 702 responses from North
      American radiation oncologists. Respondents were increasingly likely to report
      IMC irradiation in scenarios with greater axillary involvement. Responses varied
      widely among different European regions, the United States, and Canada (p <
      0.01). European respondents were more likely to treat the IMC (p < 0.01) than
      their North American counterparts. Academic physicians were more likely to treat
      the IMC than those in nonacademic positions (p < 0.01). CONCLUSION: The results
      of this study revealed significant international variation in attitudes regarding
      treatment of the IMC. The international patterns of variation mirror the
      divergent conclusions of studies conducted in the different regions, indicating
      that physicians may rely preferentially on evidence from local studies when
      making difficult treatment decisions. These variations in self-reported practice
      patterns indicate the need for greater data in this area, particularly from
      international cooperative trials. The cultural predispositions documented in this
      study are important to recognize, because they may continue to affect physician
      attitudes and practices, even as greater evidence accumulates.

PMID- 15465187
TI  - Incidence of internal mammary node metastases after a sentinel lymph node
      technique in breast cancer and its implication in the radiotherapy plan.
AB  - PURPOSE: To analyze the frequency in determining pathologically proven metastatic
      involvement of internal mammary nodes (IMN) after sentinel lymph node (SLN)
      technique in breast cancer and to evaluate the implications for radiotherapy (RT)
      management of patients. METHODS AND MATERIALS: Two hundred and twenty-five
      patients who underwent lymphatic mapping for early breast cancer treated with
      breast-conserving surgery and radiation (80%) or mastectomy (20%) were evaluated.
      There were two phases in the study: the validation phase (105 patients, 52 T1, 53
      T2 < or = 4 cm), and the application phase (120 patients, 70 T1, 50 T2 < or = 2.5
      cm). In the validation, if a drainage pathway to the IMN was identified, no
      biopsy was performed in this phase. In the application, if the study showed
      metastases in the IMNs, biopsy was performed. When histologically proven IMN
      metastases were detected, RT was included on the IMN chain planned with a 3D
      treatment system using conformal techniques. At the beginning of the study the
      injection site was subdermal and subsequently, the injection site was changed to
      peritumoral and intratumoral to search for IMN. RESULTS: In 31 patients of 225
      (14%) hot spots were observed in the internal mammary chain (11.5% and 17.2% in
      the validation and application phases, respectively). In the validation phase, in
      11 cases (11.5%) IMN drainage was observed, and in the application phase, in 20
      cases (17.2%). Sampling of the internal mammary basin based on lymphoscintigraphy
      results was successful in 69% of the cases (14 of 20) and revealed metastatic
      involvement in 14% (2 of 14). This represents incidence of only 1.7% (2 of 116)
      in early breast cancer patients with SLN study in the application phase. In both
      cases the axillary SLN was also positive. Both patients with metastatic
      involvement of the IMN area received RT on the IMN chain next to the remaining
      breast after conservative surgery. CONCLUSIONS: We can conclude that 14% of the
      patients with intraoperative drainage into the IMN surgical examination of the
      lymph nodes had pathologically positive metastases. The percentage in
      pathologically proven metastatic involvement of IMN after the SLN technique in
      early breast cancer is low, but it is not negligible. Moreover, it is expected to
      increase since the international recommendations have established a 3-cm cutoff
      for practicing the SLN technique. Although the real value of IMN irradiation in
      early breast cancer is not known, including this chain in postoperative
      radiotherapy is not recommended unless pathologically proven IMNs have been
      produced by the SLN technique. To avoid overdosage or underdosage in the joint
      between the medial tangential and IMN fields, an individualized 3D dosimetry
      study is mandatory to enhance dose distribution and reduce the heart volume to
      lessen side effects.

PMID- 15465188
TI  - Defining the clinical target volume for patients with early-stage breast cancer
      treated with lumpectomy and accelerated partial breast irradiation: a pathologic
      analysis.
AB  - BACKGROUND: This pathologic analysis was conducted to help define the clinical
      target volume (CTV) for partial breast irradiation (PBI) by analyzing the amount
      and distance of residual disease found at reexcision after an initial lumpectomy.
      MATERIALS AND METHODS: The study population consisted of 441 patients derived
      from a dataset of 607 consecutive cases of Stage I and II breast cancer (reviewed
      by one pathologist) who underwent reexcision (after lumpectomy) before radiation
      therapy (RT) as part of their standard breast-conserving therapy (BCT). The
      assumption in this analysis was that the maximal measured extension distance from
      the initial excision specimen margin (in the reexcision specimen) represents the
      minimum distance that needs to receive full-dose RT for PBI to be successful. In
      333 of the 441 cases, it was possible to measure this distance. Margins were
      classified as negative (carcinoma > 1/2 low-power field [LPF] from the margin),
      near (< 1/2 LPF from the margin), or positive. The amount of carcinoma near the
      final margin was quantified as the width of invasive carcinoma and number of
      ductal carcinoma in situ (DCIS) ducts near the margin and divided into three
      groups: least, intermediate, and greatest amount. RESULTS: Of the 333 cases, 119
      (35.7%) had no residual carcinoma in the reexcision specimen, 67 (20.1%) had
      maximum extension (invasive carcinoma or DCIS) distances of >0<5 mm beyond the
      initial excision cavity edge, 83 (24.9%) extended 5 to <10 mm, 34 (10.2%)
      extended 10 to <15 mm, and 30 (9.0%) extended > or =15 mm. In 90% of 134 patients
      with negative initial lumpectomy margins (per National Surgical Breast and Bowel
      Project criteria) at lumpectomy, if any residual disease was present (38.2% of
      cases), it was limited to <10 mm from the edge of the original lumpectomy margin.
      The initial lumpectomy margin status was then combined with the invasive
      carcinoma: specimen maximum dimension ratio to determine if these two criteria
      (when combined) could better identify patients with residual disease limited to
      <10 mm from the initial margin. Analyzed in this fashion, all 13 of the
      reexcision specimens (9.7%) with >10 mm of maximum extension by carcinoma beyond
      the edge of the initial excision specimen cavity could be identified.
      CONCLUSIONS: A margin of 10 mm around the tumor bed should be adequate in
      covering disease remaining in the breast after lumpectomy in >90% of patients
      treated with PBI. However, it is possible to accurately identify all patients
      with disease extending beyond 10 mm using more restrictive pathologic selection
      criteria. These results can also be used as a guide for defining the CTV for
      boost treatment after whole-breast RT and the amount of breast tissue to remove
      at reexcision.

PMID- 15465189
TI  - Changes in temporal patterns of local failure after breast-conserving therapy and
      their prognostic implications.
AB  - PURPOSE: The purpose of this analysis was to evaluate patterns and rates of
      ipsilateral breast tumor recurrence (IBTR) over time based on the type of failure
      (true recurrence/marginal miss [TR/MM] vs. elsewhere [E]) and to compare these to
      rates of contralateral failure in women with Stages I/II breast cancer treated
      with conservative surgery (CS) and radiation therapy (RT). METHODS AND MATERIALS:
      Between 1980 and 1997, 1448 patients with Stages I/II invasive breast carcinoma
      were treated with CS and RT to a median total dose of >60 Gy. IBTRs were analyzed
      in terms of their location as follows: TR/MM, referring to those occurring in the
      same quadrant, and E, referring to the development of a malignancy remote from
      the index lesion. Outcomes were characterized in terms of their temporal
      recurrence patterns and correlated with rates of contralateral breast failure
      (CL). The median follow-up was 8.5 years. RESULTS: A total of 79 ipsilateral and
      98 contralateral failures were observed during the follow-up period corresponding
      to 5-, 10-, and 15-year actuarial rates of 2%, 7%, and 10% and 4%, 9%, and 12%
      respectively. Fifty-nine ipsilateral failures (74.7%) were designated as TR/MM
      and 20 (25.3%) as E. The corresponding 5-, 10-, and 15-year actuarial rates of
      TR/MM and E failures were 2%, 5%, and 8% and 0.1%, 2%, and 3%, respectively. The
      median times to total ipsilateral, TR/MM, E, and contralateral failure were 6.5,
      5.7, 7.4, and 5.2 years, respectively. Between 0 and 5 years of follow-up, E
      failures represented 7% of the total ipsilateral failures observed. From 5-10 and
      10-15 years, E failures represented 39% and 27% of the total, respectively (p =
      0.01). Contralateral failure was significantly more likely to occur in the first
      5 years of follow-up than IBTR, accounting for 50 (63.3%) of the 79 failures in
      that interval (p = 0.02). No significant differences in survival rates were
      detected between any of the various failure types. On multivariate analysis, only
      reduced time to tumor recurrence was found to be adversely associated with
      overall survival. CONCLUSIONS: The rates and patterns of IBTR vary with time and,
      after 5 years, approach the rates of development of a contralateral breast
      cancer. E failures are, overall, less frequent than TR/MM but contribute
      increasingly to the IBTR rate after 5 years. Time to tumor recurrence is the most
      reliable predictor of prognosis after IBTR.

PMID- 15465190
TI  - Improved local control with higher doses of radiation in large-volume stage III
      non-small-cell lung cancer.
AB  - PURPOSE: It has been suggested that larger tumor volume is associated with poor
      survival in patients with non-small-cell lung cancer (NSCLC). We investigated
      whether high-dose radiation improved local control in patients with large-volume
      Stage III NSCLC. METHODS AND MATERIALS: Seventy-two patients with Stage III NSCLC
      and gross tumor volumes (GTV) of greater than 100 cc were treated with three
      dimensional conformal radiotherapy (3D-CRT). Patients were divided into two
      groups: those treated to less than 64 Gy (37 patients) and those treated to 64 Gy
      or higher (35 patients). RESULTS: The 1-year and 2-year local failure rates were
      27% and 47%, respectively, for Stage III patients treated to 64 Gy or higher, and
      61% and 76%, respectively, for those treated to less than 64 Gy (p = 0.024). The
      median survival time for patients treated to 64 Gy or higher was 20 months vs. 15
      months for those treated to less than 64 Gy (p = 0.068). Multivariate analysis
      revealed that dose and GTV are predictors of local failure-free survival. A 10 Gy
      increase in dose resulted in a 36.4% decreased risk of local failure.
      CONCLUSIONS: Our data suggest that administration of higher doses using 3D-CRT
      improves local control in Stage III NSCLC patients with large GTVs.

PMID- 15465191
TI  - Regional differences in lung radiosensitivity after radiotherapy for non-small
      cell lung cancer.
AB  - PURPOSE: To study regional differences in lung radiosensitivity by evaluating the
      incidence of radiation pneumonitis (RP) in relation to regional dose
      distributions. METHODS AND MATERIALS: Registered chest CT and single photon
      emission CT lung perfusion scans were obtained in 106 patients before curative or
      radical radiotherapy for non-small-cell lung cancer. The mean lung dose (MLD) was
      calculated. The single photon-emission CT perfusion data were used to weigh the
      MLD with perfusion, resulting in the mean perfusion-weighted lung dose. In
      addition, the lungs were geometrically divided into different subvolumes. The
      mean regional dose (MRD) for each region was calculated and weighted with the
      perfusion of each region to obtain the mean perfusion-weighted regional dose. RP
      was defined as respiratory symptoms requiring steroids. The incidence of RP for
      patients with tumors in a specific subvolume was calculated. The normal tissue
      complication probability (NTCP) parameter values for the TD(50), and an offset
      NTCP parameter for tumor location were fitted for both lungs and for each lung
      subvolume to the observed data using maximum likelihood analysis. RESULTS: The
      incidence of RP correlated significantly with the MLD and MRD of the posterior,
      caudal, ipsilateral, central, and peripheral lung subvolumes (p between 0.05 and
      0.002); no correlation was seen for the anterior, cranial, and contralateral
      regions Similarly, a statistically significant correlation was observed between
      the incidence of RP and the perfusion-weighted MLD and perfusion-weighted MRD for
      all regions, except the anterior lung region. For this region, the dose-effect
      relation improved remarkably after weighting the local dose with the local
      perfusion. A statistically significant difference (p = 0.01) in the incidence of
      RP was found between patients with cranial and caudal tumors (11% and 40%,
      respectively). Therefore, a dose-independent offset NTCP parameter for caudal
      tumors was included in the NTCP model, improving most correlations significantly,
      confirming that patients with caudal tumors have a greater probability of
      developing RP. CONCLUSION: The incidence of RP correlated significantly with the
      MLD and MRD of most lung regions, except for the anterior, cranial, and
      contralateral regions. Weighting the local dose with the local perfusion improved
      the dose-effect relation for the anterior lung region. Irradiation of caudally
      located lung tumors resulted in a greater risk of RP than irradiation of tumors
      located in other parts of the lungs.

PMID- 15465192
TI  - Time course of serum cytokines in patients receiving proton or combined
      photon/proton beam radiation for resectable but medically inoperable non-small
      cell lung cancer.
AB  - PURPOSE: We prospectively measured the levels of basic fibroblast growth factor
      (bFGF), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL
      10, and procollagen III peptide (P III P) in serum from non-small-cell lung
      cancer patients treated with photons combined with protons or protons alone.
      These factors were quantified because they may be extremely important in the
      development of side effects, and the treated volume integral dose may be crucial
      in inducing them. METHODS: Of the 12 participating patients, 6 with squamous cell
      carcinoma (SCC) and 3 with adenocarcinoma received combined photon/proton beam
      radiation, whereas 2 with SCC and 1 with large-cell carcinoma (LCC) received only
      proton radiation. Mean age was 73.6 years. There were 4 male and 8 female
      patients with a mean smoking history of 87.0 packyears. Nine patients had Stage
      I, 2 had Stage II, and 1 had stage IIIA lung cancer. Serum samples were obtained
      at baseline and on Days 15, 30, 45, 60, 90, 120, 150, 180, and 210 after
      initiation of radiation therapy. Injury scores for pneumonitis and fibrosis based
      on computed tomography (CT) scans were assigned. RESULTS: The percentage of lung
      volume irradiated was significantly less for patients treated with protons alone
      compared with those receiving photon plus proton therapy (p < 0.001). Injury
      scores were also lower for proton only treatment (p = 0.039). When evaluated
      collectively, bFGF, TNF-alpha, and IL-6 concentrations were significantly higher
      in the photon/proton group (p < 0.05 or less); radiation regimen, but not time
      after treatment initiation, was a significant factor in their levels. P III P
      level was also higher in the photon/proton patients (p < 0.001) and both
      radiation regimen (p = 0.027) and time after treatment (p = 0.019) had an impact.
      CONCLUSIONS: Although significant changes occurred in some of the measured
      cytokines and P III P, it was the difference in the volume integral dose that
      occurred when protons were used alone vs. mixed photon/proton therapy that
      correlated with the incidence of pneumonitis and/or fibrosis. However, it cannot
      be ruled out that differences in cytokine levels before radiotherapy initiation
      may have contributed to the outcome.

PMID- 15465193
TI  - Prostate volume measurement by transrectal ultrasound and computed tomography
      before and after permanent prostate brachytherapy.
AB  - PURPOSE: To quantify prostate volume (pvol) changes with transrectal ultrasound
      (TRUS) immediately after permanent prostate brachytherapy (PPB) and to correlate
      these changes with postimplant computed tomography (CT) volumetrics. To provide
      data relevant to evaluating the potential of TRUS-based image fusion for
      intraoperative dosimetry. METHODS AND MATERIALS: Between July 2000 and January
      2003, 177 patients underwent (125)I PPB monotherapy at our institution, and 165
      patients provided research authorization. A total of 136 patients (82%) completed
      4 imaging studies: planning TRUS, intraoperative pre- and postimplant TRUS, and
      CT. RESULTS: Mean planning TRUS pvol was 38.7 +/- 11.7 cc standard deviation
      (SD), 95% confidence interval (CI) (36.7, 40.7). Mean intraoperative TRUS pvol
      preimplant was 37.1 +/- 11.7 cc SD, 95% CI (35.1, 39.0), and postimplant was 44.5
      +/- 15.1 cc SD, 95% CI (42.0, 47.1). The mean ratio of postimplant:preimplant
      intraoperative TRUS pvols was 1.2 +/- 0.2 SD, 95% CI (1.18, 1.24), and the
      difference in mean values was 7.5 cc (p < 0.0001). CT performed within 1 day
      revealed a mean pvol of 47.9 +/- 15.7 cc SD, 95% CI (45.2, 50.5). The mean
      volumetric ratio of CT to postimplant TRUS pvol was 1.13 +/- 0.36, 95% CI (1.07
      1.19). CONCLUSIONS: Whereas mean preimplant step-section TRUS pvol measurements
      are similar, postimplant TRUS and CT measurements have greater variability that
      depend on initial pvol. CT-based pvol measurements determined a mean of 10.6
      hours after implant were more likely to be identical to those of immediate
      postimplant TRUS in prostates >33 cc. These data are relevant for establishing
      accuracy in image-fusion based approaches being investigated for real-time
      intraoperative PPB dosimetry.

PMID- 15465195
TI  - Ultrasound probe pressure as a source of error in prostate localization for
      external beam radiotherapy.
AB  - PURPOSE: A pelvic phantom was constructed to evaluate the effect of ultrasound
      probe pressure during performance of bipolar acquisition technique (BAT) for
      prostate localization for radiotherapy. METHODS AND MATERIALS: A pelvic phantom
      of a gelatin mold with a water-filled balloon representing the bladder and rectum
      and a central encapsulated clay sphere representing the prostate was constructed.
      This phantom was then scanned using planning computed tomography (CT). The
      geometric information of the phantom was outlined in two planes. The phantom was
      then scanned using the BAT system with mild and moderate ultrasound probe
      pressure. Differences in prostate depth between the CT and BAT systems were
      displayed. RESULTS: A difference of 1 cm between the phantom surface and the
      prostate could be produced with moderate ultrasound probe pressure. The
      differences were similar between the CT- and BAT-generated contours and were
      dependent on the ultrasound probe pressure. CONCLUSION: Care must be taken not to
      cause any alteration in prostate localization with increasing ultrasound probe
      pressure when using BAT localization. Increased probe pressure may introduce
      errors in prostate localization and under dose the target.

PMID- 15465194
TI  - Intensity-modulated radiotherapy as primary treatment for prostate cancer: acute
      toxicity in 114 patients.
AB  - INTRODUCTION: Dose escalation improves local control in prostate cancer. At Ghent
      University Hospital, intensity-modulated radiotherapy (IMRT) is used to increase
      the dose to the prostate and/or seminal vesicles. We report on acute toxicity in
      114 patients who received IMRT for prostate cancer. METHODS AND MATERIALS:
      Intensity-modulated radiotherapy was initiated after approval of our ethics
      committee. A class solution was used to plan all cases. Three beams (gantry 0
      degrees , 116 degrees , and 244 degrees ) and anatomy-based segmentation were
      used to create an intensity-modulated dose distribution. Maximal rectal dose was
      set at 2 Gy per fraction. Detailed dose-volume histograms for all relevant
      structures were present. For all patients, we determined the pretreatment
      morbidity by a detailed preradiotherapy, in-house developed symptom scale. All
      patients were treated with 18 MV photons of an Elekta linear accelerator.
      Patients were seen on a weekly basis during treatment, and 1 month (M1) and 3
      months (M3) thereafter. The registration of acute toxicity was standardized by a
      fixed questionnaire. The Radiation Therapy Oncology Group (RTOG) toxicity scale
      served as a basis, but additional symptoms, such as rectal blood loss, urgency,
      and incontinence, were scored as well. RESULTS: All 114 IMRT plans were delivered
      successfully without any interruption or technical problem. Daily treatment time
      was always less than 8 min and less than 6 min in 90% of the cases. Grade 1 and
      Grade 2 gastrointestinal (GI) toxicities were observed in 44% and 29% of the
      patients, respectively, during the whole period. If only the RTOG scale was used,
      Grade 1 and Grade 2 GI toxicities were noted in 39% and 27% of the patients,
      respectively, leaving 34% free of acute RTOG-scaled toxicity. Grade 3
      genitourinary (GU) toxicity was seen in 8 patients (7%), all but 1 during
      treatment. Grade 2 and Grade 1 GU toxicities were seen in 36% and 47% of the
      patients, respectively, leaving only 10% free of acute GU toxicity. DISCUSSION:
      Anatomy-based IMRT to treat prostate cancer is incorporated into our daily
      routine without any problem. Acute toxicity is very low. Most of the recorded
      symptoms decrease over time, except for GI urgency and incontinence. The
      incorporation of additional symptoms makes the scoring more detailed.

PMID- 15465196
TI  - Clinical implementation of intensity-modulated arc therapy (IMAT) for rectal
      cancer.
AB  - PURPOSE: In rectal cancer, combined radiotherapy and chemotherapy, either pre- or
      postoperatively, is an accepted treatment. Late small bowel (SB) toxicity is a
      feared side effect and limits radiation-dose escalation in a volume-dependent
      way. A planning strategy for intensity- modulated arc therapy (IMAT) was
      developed, and IMAT was clinically implemented with the aim to reduce the volume
      of SB irradiated at high doses and thus reduce SB toxicity. We report on the
      treatment plans of the first 7 patients, on the comparison of IMAT with
      conventional 3D planning (3D), and on the feasibility of IMAT delivery. METHODS
      AND MATERIALS: Seven patients, who were referred to our department for
      preoperative (n = 4) or postoperative (n = 3) radiotherapy for rectal cancer,
      gave written consent for IMAT treatment. All patients had a planning CT in prone
      position. The delineation of the clinical target volume was done after fusion of
      CT and MRI, with the help of a radiologist. For the IMAT plan, arcs were
      generated using an anatomy-based segmentation tool. The optimization of the arcs
      was done by weight optimization (WO) and leaf position optimization (LPO), both
      of which were adapted for IMAT purposes. The 3D plans used one posterior and two
      lateral wedged beams, of which the outlines were shaped to the beam's-eye view
      projection of the planning target volume (PTV). Beam WO was done by constrained
      matrix inversion. For dose-volume histogram analysis, all plans were normalized
      to 45 Gy as median PTV dose. Polymer gel dosimetry (PGD) on a humanoid phantom
      was used for the validation of the total chain (planning to delivery). IMAT
      treatments were delivered by an Elekta SliPlus linear accelerator using prototype
      software with the same interlock class as in clinical mode. RESULTS: The IMAT
      plan resulted in 3 to 6 arcs, with a mean delivery time of 6.3 min and a mean of
      456 monitor units (MU) for a 180 cGy fraction. The minimal dose in the PTV was
      not significantly different between 3D and IMAT plans. Inhomogeneity was highest
      for the IMAT plans (14.1%) and lowest for the 3D plans (9.9%). Mean dose to the
      SB was significantly lower for the IMAT plans (12.4 Gy) than for the 3D plans
      (17.0 Gy). The volume of SB receiving less than any dose level was lower for the
      IMAT plans than for 3D plans. Integral dose was lower in the IMAT plans than for
      the 3D plans (respectively 244 J and 262 J to deliver 45 Gy). Differences between
      the PGD measured dose and the calculated dose were as small for IMAT as for 3D
      treatments. CONCLUSION: IMAT plans are deliverable within a 5-10-minute time
      slot, and result in a lower dose to the SB than 3D plans, without creating
      significant underdosages in the PTV. PGD showed that IMAT delivery is as accurate
      as 3D delivery.

PMID- 15465197
TI  - Biochemical signs of impaired cobalamin status during and after radiotherapy for
      rectal cancer.
AB  - PURPOSE: The aim of the study was to investigate whether pelvic radiotherapy for
      rectal cancer had a negative impact on cobalamin status. METHODS AND MATERIALS:
      Consecutive patients receiving pelvic radiotherapy (50 Gy) for rectal cancer were
      evaluated prospectively (n = 54). Serum cobalamin, holotranscobalamin (holoTC),
      methylmalonic acid (MMA), and total homocysteine (tHcy) were measured at start
      and end of radiotherapy, at follow-up 4-6 weeks and 1 year (n = 23) after
      radiotherapy. RESULTS: Mean serum cobalamin decreased from 306 pmol/L before
      treatment to 267 pmol/L at the end of radiotherapy (p < 0.001), 247 pmol/L 4-6
      weeks after radiotherapy (p < 0.001), and 249 pmol/L 1 year after radiotherapy (p
      = 0.02). Mean serum MMA was 0.16 micromol/L pretreatment, 0.17 micromol/L at the
      end of radiotherapy (n.s.), and increased to 0.19 micromol/L after 4-6 weeks (p =
      0.007), and to 0.21 micromol/L after 1 year (p < 0.001). There was no change in
      serum tHcy. Mean serum holoTC was reduced from 111 pmol/L pretreatment to 93
      pmol/L 4-6 weeks after radiotherapy (p = 0.002). CONCLUSIONS: The data suggest
      rapid and persistent decrease in cobalamin status after radiotherapy for rectal
      cancer, as reflected by reduced serum cobalamin combined with increased serum
      MMA. This observation, though modest, may motivate routine monitoring of
      cobalamin status at follow-up after radiotherapy.

PMID- 15465198
TI  - Concurrent weekly cisplatin and radiotherapy in routine management of cervical
      cancer: a report on patient compliance and acute toxicity.
AB  - PURPOSE: To evaluate patient compliance and acute toxicity accompanying
      concurrent weekly cisplatin and radiotherapy (RT) in the routine management of
      cervical cancer. METHODS AND MATERIALS: Locally advanced or high-risk early-stage
      cervical cancer patients treated with RT and concurrent weekly cisplatin at a
      dose of 40 mg/m(2) i.v. (maximum dose, 70 mg) for five cycles. Definitive RT
      included whole pelvis external beam RT to the International Commission on
      Radiation Units and Measurements reference dose of 40 Gy plus a 10-Gy boost to
      the parametrium and two brachytherapy applications of 20 Gy to point A each.
      Postoperative RT consisted of pelvic external beam RT to the International
      Commission on Radiation Units and Measurements reference dose of 50 Gy and one
      brachytherapy application of 30 Gy at a depth of 0.5 cm from the applicator
      surface. RESULTS: Included in this analysis were 112 consecutive cervical cancer
      patients treated at one institution with concurrent cisplatin and RT between May
      1999 and September 2002. The median age was 48 years (range, 28-79 years).
      Definitive RT was administered to 57 International Federation of Gynecology and
      Obstetrics "bulky" Stage IB or IIB-IVA patients, and 53 patients underwent
      postoperative RT; 2 patients underwent RT for stump carcinoma. All but 2 patients
      (both administered definitive RT) completed RT. A total of 454 cisplatin cycles
      were administered (median 4 cycles/patient, range 1-6). Overall, 74% of patients
      received at least four cycles of cisplatin. The planned five cisplatin cycles
      were administered to 50 patients (45%); 42% were irradiated definitively and 47%
      postoperatively. The full and timely planned cisplatin dose was administered to
      29 patients (26%). For 29% of patients, the interval between cycles was prolonged
      because of toxicity (n = 11; 10%) or for reasons not related to toxicity (n = 10;
      9%). Of the 112 patients, 62 (55%) did not undergo the planned five cycles of
      cisplatin because of treatment toxicity (n = 35; 31%) or noncompliance with the
      treatment schedule because of delayed administration of the first cycle or
      omission of a cycle for reasons other than toxicity (n = 23; 21%). The most
      common side effects resulting in chemotherapy discontinuation included GI
      complications (n = 7) and impaired renal function (n = 5). Of the 112 patients,
      49 (44%) experienced Grade 1 or 2 leukopenia and 6 (5%) Grade 3 or 4 leukopenia.
      CONCLUSION: Our results show that pelvic RT combined with weekly cisplatin in
      cervical cancer patients is accompanied by considerable acute toxicity.
      Furthermore, a number of patients were unable to comply with the treatment
      schedule owing to reasons unrelated to treatment toxicity. Thus, administration
      of the full chemotherapy dose may be difficult, although the delivery of planned
      RT was generally not compromised. Additional follow-up is needed to assess the
      late toxicity of combined modality treatment.

PMID- 15465199
TI  - Differential cyclooxygenase-2 expression in squamous cell carcinoma and
      adenocarcinoma of the uterine cervix.
AB  - PURPOSE: To determine the differential expression of cyclooxygenase-2 (COX-2) in
      patients with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the
      uterine cervix and the prognostic significance of COX-2 expression in these
      histologic types. METHODS AND MATERIALS: A total of 105 International Federation
      of Gynecology and Obstetrics Stage IIB uterine cervical cancer patients were
      screened for COX-2 expression immunohistochemically. COX-2 expression was
      determined in invasive cervical SCC (n = 84) and invasive cervical ADC (n = 21).
      To determine the clinical significance of COX-2 expression by histologic type,
      the patients were arbitrarily divided into four groups: SCC/COX-2 negative (n =
      64); SCC/COX-2 positive (n = 20); ADC/COX-2 negative (n = 9); and ADC/COX-2
      positive (n = 12). The clinical response to treatment, patterns of treatment
      failure, and survival data by COX-2 expression were compared for these two major
      histologic types. Univariate and multivariate analyses were performed to identify
      the prognostic factors influencing survival. RESULTS: Immunohistochemical
      examination showed that COX-2 expression was more frequently observed in ADC than
      in SCC (57% vs. 24%, p = 0.007). Moreover, COX-2 expression was an important
      predictor of treatment response, irrespective of the histologic type. All COX-2
      negative patients achieved complete remission after initial treatment; 17% of SCC
      patients and 33% of ADC patients with COX-2 expression did not have complete
      remission after the initial treatment. The incidence of local failure for those
      with COX-2 expression was significantly greater than for COX-2-negative patients,
      regardless of histologic type. With a minimal follow-up of 60 months, the overall
      5-year actuarial survival rate for SCC and ADC patients was 79% and 62%,
      respectively (p = 0.05). The 5-year disease-free survival rate for SCC and ADC
      patients was 73% and 56%, respectively (p = 0.13). Irrespective of the pathologic
      type, COX-2-positive patients had an unfavorable prognosis. The overall 5-year
      actuarial survival rate was 57% for COX-2-positive patients and 83% for COX-2
      negative patients (p = 0.001). When patients were stratified into the four groups
      according to histologic type and COX-2 expression status, ADC/COX-2-positive
      patients had the worst prognosis, with an overall 5-year actuarial survival rate
      of 49% compared with 78% for ADC/COX-2-negative patients, 62% for SCC/COX-2
      positive, and 84% for SCC/COX-2-negative patients (p = 0.007, log-rank test).
      Irrespective of histologic type, COX-2 expression was an independent prognostic
      factor by univariate and multivariate analyses. CONCLUSION: In uterine cervical
      cancer, COX-2 was expressed in a greater proportion of ADC patients than SCC
      patients. COX-2 expression was also identified as a major determiner of a poor
      response to treatment and of an unfavorable prognosis, irrespective of the
      histologic type, reflecting the importance of the COX-2 protein in the
      acquisition of biologic aggressiveness and more malignant phenotype or increased
      resistance to the standard chemotherapy and radiotherapy in both histologic
      types. Given these observations, we believe that that ADC/COX-2-positive patients
      might be appropriate candidates for future trials of selective COX-2 inhibitor
      adjunctive therapy.

PMID- 15465200
TI  - Definitive irradiation in multidisciplinary management of localized Ewing sarcoma
      family of tumors in pediatric patients: outcome and prognostic factors.
AB  - PURPOSE: To assess the effect of radiation dose on local tumor control of the
      Ewing sarcoma family of tumors in 79 patients with localized disease treated at a
      single institution. METHODS AND MATERIALS: Thirty-seven patients received
      vincristine, actinomycin D, cyclophosphamide, and doxorubicin, and 42 received
      vincristine, actinomycin D, and cyclophosphamide, with alternating cycles of
      ifosfamide and etoposide; all underwent definitive radiotherapy (median dose,
      37.5 Gy) with either low-dose (<40 Gy) or standard dose (> or =40 Gy) radiation
      delivered according to the protocol. We calculated the cumulative incidence of
      local treatment failure, disease recurrence, and overall survival and analyzed
      the effect of known prognostic factors and radiation dose. RESULTS: The
      cumulative incidence of local treatment failure at 10 years was 30.4% and that of
      disease recurrence was 40%. The overall survival rate was 64.5%. Patient age > or
      =14 years and tumor size > or =8 cm were adverse prognostic factors for local
      treatment failure; patient age > or =14 years was also associated with worse
      survival. Although the radiation dose alone did not predict for local treatment
      failure, the cumulative incidence of local failure at 10 years was 19% when
      tumors <8 cm were treated with <40 Gy, and no patient treated with standard doses
      (> or =40 Gy) developed local recurrence (p = 0.084). CONCLUSION: Tumor size and
      patient age predict for local tumor control in patients with Ewing sarcoma family
      of tumors treated with systemic therapy and definitive radiotherapy. Patients
      treated with reduced-dose radiotherapy experienced unacceptably high rates of
      local recurrence.

PMID- 15465201
TI  - Prospective study of combined modality treatment or radiotherapy alone in the
      management of early-stage adult Hodgkin's disease.
AB  - PURPOSE: To determine the efficacy and toxicity of combined modality treatment
      (CMT) or radiotherapy (RT) alone in the management of clinical Stage I-IIA adult
      Hodgkin's disease patients. METHODS AND MATERIALS: Forty-seven patients with
      supradiaphragmatic clinical Stage I-IIA Hodgkin's disease without bulky
      mediastinal lymphadenopathy were enrolled into this prospective study between
      September 1997 and February 2002. Patients with very favorable criteria
      presenting with one or two nonbulky nodal areas involved, an erythrocyte
      sedimentation rate of <50 mm/h, age <40 years, and either lymphocyte predominant
      or nodular sclerosing histologic findings were treated by RT alone. Patients
      missing any of these favorable criteria were classified as the other favorable
      group and were treated with three courses of doxorubicin, bleomycin, vinblastine,
      and dacarbazine chemotherapy followed by involved-field RT. The median age was 36
      years (range, 19-53 years). Of the 47 patients, 15 were women and 32 were men.
      Only 3 patients were classified as the most favorable group and treated with
      mantle RT alone; the remaining 44 were treated with CMT. RESULTS: The median
      follow-up was 51 months (range, 20-74 months). Only 2 patients developed
      recurrence, both out of the irradiated field, one in the contralateral neck and
      the other in the abdomen. The 5-year relapse-free and overall survival rate was
      95.4% and 97.8%, respectively. Although none of the prognostic factors were
      statistically significant for relapse-free survival, a trend was noted for the
      response to chemotherapy (p = 0.06). Only 2 patients developed treatment-related
      complications. One patient treated with mantle RT alone developed severe ischemic
      heart disease and one in the CMT arm developed subclinical hypothyroidism.
      CONCLUSION: Despite the short follow-up, CMT or RT alone tailored according to
      the clinical prognostic factors were successful in terms of disease control in
      clinical Stage I-IIA Hodgkin's disease. Longer follow-up is required to make
      definitive conclusions.

PMID- 15465202
TI  - Pilot study of modified version of CHOP plus radiotherapy for early-stage
      aggressive non-Hodgkin's lymphoma of the head and neck.
AB  - PURPOSE: To evaluate the safety and efficacy of a modified version of
      cyclophosphamide, doxorubicin, vincristine, prednisone (pirarubicin,
      cyclophosphamide, vincristine, and prednisone [THP-COP]) plus radiotherapy for
      early-stage aggressive non-Hodgkin's lymphoma of the head and neck. METHODS AND
      MATERIALS: Between December 1993 and December 1999, 41 patients with early-stage
      non-Hodgkin's lymphoma with intermediate-grade histologic features were enrolled
      in our study. The mean patient age was 51 years. Of the 41 patients, 27 had Stage
      I and 14 Stage II disease. The primary site was Waldeyer's ring, a neck node, or
      an extranodal site in 14, 11, and 16 patients, respectively. The immunophenotype
      was B cell in 29 and T cell in 12 patients. All patients were in the low-risk
      category according to the International Prognostic Index. Chemotherapy consisted
      of 40 mg/m(2) i.v. pirarubicin (THP-Adriamycin), 750 mg/m(2) i.v.
      cyclophosphamide, and 1.0 mg/m(2) i.v. vincristine, on Day 1 and 40 mg/m(2) p.o.
      prednisone on Days 1-5. The combination chemotherapy was given twice at a 14-day
      interval. Radiotherapy was given to involved areas at a fraction size of 2.0-2.5
      Gy up to a total of 40 Gy within 4-5 weeks. The mean follow-up period was 63
      months. RESULTS: The 5-year overall survival rate was 89%. The 5-year cause
      specific survival and progression-free survival rate was 90% and 81%,
      respectively. The 5-year progression-free survival rate for patients with
      Waldeyer's ring primaries was 93%. Patients with tumor <5 cm in size had greater
      5-year progression-free survival than those with tumor >5 cm in size (85% vs.
      33%, p <0.05, log-rank test). Grade 4 neutropenia was seen in 12% of patients;
      however, 93% of patients (38 of 41) received chemotherapy as scheduled with the
      support of granulocyte colony-stimulating factor. CONCLUSION: Biweekly THP-COP
      plus radiotherapy is feasible and effective for Stage I-II low-risk non-Hodgkin's
      lymphoma.

PMID- 15465203
TI  - Randomized comparison of stereotactic radiosurgery followed by conventional
      radiotherapy with carmustine to conventional radiotherapy with carmustine for
      patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group
      93-05 protocol.
AB  - PURPOSE: Conventional treatment of glioblastoma multiforme (GBM) cures less than
      5% of patients. We investigated the effect of stereotactic radiosurgery (SRS)
      added to conventional external beam radiation therapy (EBRT) with carmustine
      (BCNU) on the survival of patients with GBM. METHODS AND MATERIALS: A total of
      203 patients with supratentorial GBM (tumor < or =40 mm) were randomly assigned
      either to postoperative SRS followed by EBRT (60 Gy) plus BCNU (80 mg/m(2) Days 1
      3 every 8 weeks for six cycles) or to EBRT with BCNU alone. The dose of
      radiosurgery was tumor size-dependent and ranged from 15 Gy for largest to 24 Gy
      for smallest tumors. RT and BCNU were identical in both arms. RESULTS: At a
      median follow-up time of 61 months, the median survival in the radiosurgery group
      was 13.5 months (95% confidence interval, 11.0-14.8) as compared with 13.6 months
      (95% confidence interval, 11.2-15.2, p = 0.5711) for the standard treatment
      group. There were also no significant differences in 2- and 3-year survival rates
      and in patterns of failure between the two arms. Quality of life deterioration
      and cognitive decline at the end of therapy, compared with baseline, were
      comparable and there was no difference in quality-adjusted survival between the
      arms. CONCLUSIONS: Stereotactic radiosurgery followed by EBRT and BCNU does not
      improve the outcome in patients with GBM nor does it change the general quality
      of life or cognitive functioning.

PMID- 15465204
TI  - Stereotactic irradiation for intracranial arteriovenous malformation using
      stereotactic radiosurgery or hypofractionated stereotactic radiotherapy.
AB  - PURPOSE: To investigate the appropriateness of the treatment policy of
      stereotactic irradiation using both hypofractionated stereotactic radiotherapy
      (HSRT) and stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs)
      located in an eloquent region or for large AVMs and using SRS alone for the other
      AVMs. METHODS AND MATERIALS: Included in this study were 75 AVMs in 72 patients,
      with a mean follow-up of 52 months. Of the 75 AVMs, 33 were located in eloquent
      regions or were >2.5 cm in maximal diameter and were given 25-35 Gy (mean, 32.4
      Gy) in four daily fractions at a single isocenter if the patient agreed to
      prolonged wearing of the stereotactic frame for 5 days. The other 42 AVMs were
      treated with SRS at a dose of 15-25 Gy (mean, 24.1 Gy) at the isocenter. The 75
      AVMs were classified according to the Spetzler-Martin grading system; 21, 23, 28,
      2, and 1 AVM were Grade I, II, III, IV, V, and VI, respectively. RESULTS: The
      overall actuarial rate of obliteration was 43% (95% confidence interval [CI], 30
      56%) at 3 years, 72% (95% CI, 58-86%) at 5 years, and 78% (95% CI, 63-93%) at 6
      years. The actuarial obliteration rate at 5 years was 79% for the 42 AVMs <2.0 cm
      and 66% for the 33 AVMs >2 cm. The 5- and 6-year actuarial obliteration rate was
      61% (95% CI, 39-83%) and 71% (95% CI, 47-95%), respectively, after HSRT and 81%
      (95% CI, 66-96%) and 81% (95% CI, 66-96%), respectively, after SRS; the
      difference was not statistically significant. Radiation-induced necrosis was
      observed in 4 subjects in the SRS group and 1 subject in the HSRT group. Cyst
      formation occurred in 3 patients in the SRS group and no patient in the HSRT
      group. A permanent symptomatic complication was observed in 3 cases (4.2%), and 1
      of the 3 was fatal. All 3 patients were in the SRS group. The annual intracranial
      hemorrhage rate was 5.5-5.6% for all patients. CONCLUSION: Our treatment policy
      using SRS and HSRT was as effective as the policy involving SRS alone. The HSRT
      schedule was suggested to have a lower frequency of radiation necrosis and cyst
      formation than the high-dose SRS schedule. The benefit of HSRT compared with
      lower dose SRS has not yet been determined.

PMID- 15465205
TI  - The efficacy of hyperbaric oxygen therapy in the treatment of radiation-induced
      late side effects.
AB  - PURPOSE: We investigated the efficacy of hyperbaric oxygen therapy (HBOT) in the
      management of patients with radiation-induced late side effects, the majority of
      whom had failed previous interventions. METHODS AND MATERIALS: Of 105 eligible
      subjects, 30 had either died or were not contactable, leaving 75 who qualified
      for inclusion in this retrospective study. Patients answered a questionnaire
      documenting symptom severity before and after treatment (using Radiation Therapy
      Oncology Group criteria), duration of improvement, relapse incidence, and HBOT
      related complications. RESULTS: The rate of participation was 60% (45/75).
      Improvement of principal presenting symptoms after HBOT was noted in 75% of head
      and-neck, 100% of pelvic, and 57% of "other" subjects (median duration of
      response of 62, 72, and 68 weeks, respectively). Bone and bladder symptoms were
      most likely to benefit from HBOT (response rate, 81% and 83%, respectively).
      Fifty percent of subjects with soft tissue necrosis/mucous membrane side effects
      improved with HBOT. The low response rate of salivary (11%), neurologic (17%),
      laryngeal (17%), and upper gastrointestinal symptoms (22%) indicates that these
      were more resistant to HBOT. Relapse incidence was low (22%), and minor HBOT
      related complications occurred in 31% of patients. CONCLUSION: Hyperbaric oxygen
      therapy is a safe and effective treatment modality offering durable relief in the
      management of radiation-induced osteoradionecrosis either alone or as an
      adjunctive treatment. Radiation soft tissue necrosis, cystitis, and proctitis
      also seemed to benefit from HBOT, but the present study did not have sufficient
      numbers to reliably predict long-term response.

PMID- 15465206
TI  - Permanent alopecia after cranial irradiation: dose-response relationship.
AB  - PURPOSE: To develop a dose-response relationship for the occurrence of permanent
      alopecia after cranial irradiation and to analyze potential confounding variables
      that may contribute to this unwanted and often unavoidable complication of
      treatment. METHODS AND MATERIALS: Twenty-six patients were enrolled in this
      study. Three reviewers independently assessed 61 scalp regions and assigned a
      score for the degree of alopecia in each region using a 4-point scale. Patient
      and treatment data were collected using a patient questionnaire and outpatient
      medical chart review. The hair follicle dose was calculated for each scalp region
      and correlated with the alopecia score for that region. A dose-response
      relationship was established using the data from these correlations. RESULTS:
      Permanent alopecia correlated significantly with the follicle dose only (p <
      0.001). A personal history of alopecia and the use of chemotherapy correlated
      with permanent alopecia with borderline statistical significance (p = 0.059 and p
      = 0.068, respectively). Patient age, family history of baldness, gender, tobacco
      use, diabetes, and beam energy did not correlate with alopecia. CONCLUSION: We
      report the first human dose-response relationship describing the effect of the
      follicle dose on the subsequent development of permanent scalp alopecia after
      cranial irradiation. This information will assist the radiation oncologist,
      physicist, and dosimetrist in designing a treatment plan that might minimize the
      risk of this untoward side effect of cranial irradiation.

PMID- 15465207
TI  - Radiotherapy vs. nonsteroidal anti-inflammatory drugs for the prevention of
      heterotopic ossification after major hip procedures: a meta-analysis of
      randomized trials.
AB  - PURPOSE: To evaluate the efficacy of radiotherapy (RT) vs. nonsteroidal anti
      inflammatory drugs (NSAIDs) in the prevention of heterotopic ossification (HO)
      after major hip procedures. METHODS AND MATERIALS: We conducted a meta-analysis
      of 7 randomized studies (n = 1143) comparing RT with NSAIDs. Data were combined
      across studies using fixed and random effects models. We conducted separate
      analyses for clinically significant HO (Brooker Grade 3 and 4) and for any HO
      (any Brooker grade). RESULTS: Overall RT tended to be more effective than NSAIDs
      in preventing Brooker 3 or 4 HO (risk ratio, 0.42; 95% confidence interval [CI],
      0.18-0.97) or any HO (risk ratio, 0.75; 95% CI, 0.37-1.71), but with significant
      between-study heterogeneity for the second analysis. The overall absolute risk
      difference for Brooker 3 or 4 HO was small (-1.18%; 95% CI, -2.45% to 0.09%).
      Subgroup analyses showed that early preoperative RT (16-20 hours before surgery)
      and acetylsalicylic acid were less effective. For postoperative RT, there was a
      significant dose-response relationship (p = 0.008): 6 Gy of RT was equally
      effective as NSAIDs, whereas increasing radiation doses were more effective.
      CONCLUSIONS: Although absolute differences may be small, postoperative RT is on
      average more effective than NSAIDs in preventing HO after major hip procedures,
      and its efficacy is dose dependent.

PMID- 15465208
TI  - Antigenic expression of human metastatic prostate cancer cell lines for in vitro
      multiple-targeted alpha-therapy with 213Bi-conjugates.
AB  - PURPOSE: Control of metastatic prostate cancer (CaP) is an elusive objective.
      Some 30% of patients with clinically localized CaP will develop micrometastatic
      disease. Defining the expression of tumor-associated antigens on CaP will enable
      appropriate selection of therapeutic targets. METHODS AND MATERIALS: The
      expression of tumor-associated antigens on CaP cell lines (PC-3, DU 145, and
      LNCaP-LN3) was detected by immunohistochemistry and flow cytometry. Test and
      control alpha-conjugates were prepared using monoclonal antibodies, an inhibitor,
      plasminogen activator inhibitor type 2, that binds to the cell-membrane-bound
      protease, urokinase plasminogen activator, and a control protein labeled with
      (213)Bi using standard methods. These were used singly or together against three
      different CaP cell lines in vitro. The cytotoxicity of the alpha-conjugates was
      assessed using the [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium, inner salt] (MTS) assay. RESULTS: The PC-3 and DU
      145 cancer cell lines expressed antigens that bind monoclonal antibodies BLCA-38
      and #394 (mouse anti-human urokinase plasminogen activator B-chain) but not J591.
      The LNCaP-LN3 cells bound J591 but not #394 or BLCA-38. For the PC-3, DU 145, and
      LNCaP-LN3 cell lines, multiple-targeted alpha-therapy combining four alpha
      conjugates (one-quarter doses of each) gave D(0) (37% cell survival) values of
      15, 17, and 27 microCi/mL compared with those of the controls of 272, 289, and
      281 microCi/mL, respectively. CONCLUSION: Metastatic prostate cancer-associated
      antigens recognized by multiple monoclonal antibodies are potential targets for
      alpha-therapy. Multiple-targeted alpha-therapy produced cytotoxicity specific to
      three CaP cell lines and may form the basis of treatment for micrometastatic CaP,
      overcoming the heterogeneity of expression of the targeted antigens.

PMID- 15465209
TI  - In vivo determination of tumor oxygenation during growth and in response to
      carbogen breathing using 15C5-loaded alginate capsules as fluorine-19 magnetic
      resonance imaging oxygen sensors.
AB  - PURPOSE: The objective was to present a method for the repeated noninvasive
      measurement of tumor oxygenation (Po(2)) over the whole period of tumor growth.
      METHODS AND MATERIALS: A mixture of tumor homogenate (GH3 prolactinoma) and
      alginate capsules loaded with perfluoro-15-crown-5-ether (15C5) was injected into
      the flanks of Wistar Furth rats. The temporal behavior of tumor Po(2) was
      monitored between Day 1 and 26 after injection using fluorine-19 ((19)F) magnetic
      resonance imaging (MRI). In addition, the response of tumor Po(2) to modifiers of
      the tumor microenvironment (carbogen [95% O(2)/5% CO(2)], nicotinamide, and
      hydralazine) was investigated. RESULTS: An initial increase of tumor Po(2),
      probably reflecting neovascularization, followed by a decrease after Week 2,
      probably indicating tumor hypoxia or necrosis, were observed. The minimum and
      maximum average Po(2) +/- SEM observed were 3.3 +/- 2.0 mm Hg on Day 2 and 25.7
      +/- 3.8 mm Hg on Day 13, respectively. Carbogen increased the tumor Po(2),
      whereas nicotinamide caused no significant change and hydralazine induced a
      significant decrease in tumor oxygenation. CONCLUSIONS: A preclinical method for
      the repeated noninvasive determination of tumor Po(2) was presented. It might
      help to investigate tumor physiology and the mechanisms of modifiers of the tumor
      microenvironment and their role in different therapeutic approaches.

PMID- 15465210
TI  - Combination of the vascular targeting agent ZD6126 with boron neutron capture
      therapy.
AB  - PURPOSE: The aim of this study was to evaluate the antitumor efficacy of the
      vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) in the rodent
      squamous cell carcinoma (SCC) VII carcinoma model, in combination with boron
      neutron capture therapy (BNCT). METHODS AND MATERIALS: Sodium borocaptate-(10)B
      (BSH, 125 mg/kg, i.p.) or l-p-boronophenylalanine-(10)B (BPA, 250 mg/kg, i.p.)
      was injected into SCC VII tumor-bearing mice, and 15 min later, ZD6126 (100
      mg/kg, i.p.) was administered. Then, the (10)B concentrations in tumors and
      normal tissues were measured by prompt gamma-ray spectrometry. On the other hand,
      for the thermal neutron beam exposure experiment, SCC VII tumor-bearing mice were
      continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P)
      cells in the tumors, followed by treatment with a (10)B-carrier and ZD6126 in the
      same manner as the above-mentioned (10)B pharmacokinetics analyses. To obtain
      almost similar intratumor (10)B concentrations during neutron exposure, thermal
      neutron beam irradiation was started from the time point of 30 min after
      injection of BSH only, 90 min after BSH injection for combination with ZD6126,
      120 min after the injection of BPA only, and 180 min after BPA injection for
      combination with ZD6126. Right after irradiation, the tumors were excised,
      minced, and trypsinized. The tumor cell suspensions thus obtained were incubated
      with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency
      in cells without BrdU labeling (quiescent [Q] cells) was determined using
      immunofluorescence staining for BrdU. Meanwhile, the MN frequency in total (P +
      Q) tumor cells was determined from the tumors that were not pretreated with BrdU.
      The clonogenic cell survival assay was also performed in mice given no BrdU.
      RESULTS: Pharmacokinetics analyses showed that combination with ZD6126 greatly
      increased the (10)B concentrations in tumors after 60 min after BSH injection and
      after 120 min after BPA injection. The concentrations of (10)B from BSH in normal
      tissues were also raised by combination with ZD6126, although not so clearly as
      those in tumors. Combination with ZD6126 had almost no effect on the
      concentrations of (10)B from BPA in normal tissues. The clonogenic surviving
      fractions of total tumor cells and the MN frequencies of both total and Q tumor
      cells were reduced and increased by combination with ZD6126, respectively,
      whether BSH or BPA was employed. However, the degrees of these changes in the
      clonogenic surviving fractions and the MN frequencies were more obviously
      observed in tumors from BSH-injected mice than from BPA-injected mice, and in Q
      tumor cells than in total tumor cells regardless of the employed (10)B-carrier.
      CONCLUSIONS: Combination with ZD6126 was regarded as more promising in BSH-BNCT
      than BPA-BNCT, and more effective for enhancing the sensitivity of the Q tumor
      cells than that of the total tumor cells. This resulted in the decrease in the
      extended difference in the sensitivity between the total and Q tumor cells caused
      by the use of (10)B-carrier for BNCT.

PMID- 15465211
TI  - Placement of 125I implants with the da Vinci robotic system after video-assisted
      thoracoscopic wedge resection: a feasibility study.
AB  - PURPOSE: To evaluate the feasibility of using the da Vinci robotic system for
      radioactive seed placement in the wedge resection margin of pigs' lungs. METHODS
      AND MATERIALS: Video-assisted thoracoscopic wedge resection was performed in the
      upper and lower lobes in pigs. Dummy (125)I seeds embedded in absorbable sutures
      were sewn into the resection margin with the aid of the da Vinci robotic system
      without complications. In the "loop technique," the seeds were placed in a
      cylindrical pattern; in the "longitudinal," they were above and lateral to the
      resection margin. Orthogonal radiographs were taken in the operating room. For
      dose calculation, Variseed 66.7 (Build 11312) software was used. RESULTS: With
      looping seed placement, in the coronal view, the dose at 1 cm from the source was
      97.0 Gy; in the lateral view it was 107.3 Gy. For longitudinal seed placement,
      the numbers were 89.5 Gy and 70.0 Gy, respectively. CONCLUSION: Robotic
      technology allows direct placement of radioactive seeds into the resection margin
      by endoscopic surgery. It overcomes the technical difficulties of manipulating in
      the narrow chest cavity. With the advent of robotic technology, new options in
      the treatment of lung cancer, as well as other malignant tumors, will become
      available.

PMID- 15465212
TI  - Measurement of lung tumor motion using respiration-correlated CT.
AB  - PURPOSE: We investigate the characteristics of lung tumor motion measured with
      respiration-correlated computed tomography (RCCT) and examine the method's
      applicability to radiotherapy planning and treatment. METHODS AND MATERIALS: Six
      patients treated for non-small-cell lung carcinoma received a helical single
      slice computed tomography (CT) scan with a slow couch movement (1 mm/s), while
      simultaneously respiration is recorded with an external position-sensitive
      monitor. Another 6 patients receive a 4-slice CT scan in a cine mode, in which
      sequential images are acquired for a complete respiratory cycle at each couch
      position while respiration is recorded. The images are retrospectively resorted
      into different respiration phases as measured with the external monitor (4-slice
      data) or patient surface displacement observed in the images (single-slice data).
      The gross tumor volume (GTV) in lung is delineated at one phase and serves as a
      visual guide for delineation at other phases. Interfractional GTV variation is
      estimated by scaling diaphragm position variations measured in gated radiographs
      at treatment with the ratio of GTV:diaphragm displacement observed in the RCCT
      data. RESULTS: Seven out of 12 patients show GTV displacement with respiration of
      more than 1 cm, primarily in the superior-inferior (SI) direction; 2 patients
      show anterior-posterior displacement of more than 1 cm. In all cases, extremes in
      GTV position in the SI direction are consistent with externally measured extremes
      in respiration. Three patients show evidence of hysteresis in GTV motion, in
      which the tumor trajectory is displaced 0.2 to 0.5 cm anteriorly during
      expiration relative to inspiration. Significant (>1 cm) expansion of the GTV in
      the SI direction with respiration is observed in 1 patient. Estimated
      intrafractional GTV motion for gated treatment at end expiration is 0.6 cm or
      less in all cases; however; interfraction variation estimates (systematic plus
      random) are more than 1 cm in 3/9 patients. CONCLUSION: Respiration-correlated CT
      can be performed with currently available CT equipment and acquisition settings.
      RCCT provides not only three-dimensional information on intrafractional tumor
      motion and deformation, but also allows estimates of interfractional tumor
      variation when combined with radiographic measurements of diaphragm position
      variation during treatment.

PMID- 15465213
TI  - Monte Carlo simulations with time-dependent geometries to investigate effects of
      organ motion with high temporal resolution.
AB  - PURPOSE: To calculate the dose in time-dependent geometry, the results of three
      dimensional calculations are usually performed separately and combined. This
      approach becomes cumbersome when high temporal resolution is required, if the
      geometry is complex, or if interplay effects between different, independently
      moving systems are to be studied. The purpose of this project was the
      implementation of continuous (four-dimensional [4D]) Monte Carlo simulation to
      study the irradiation of tumors under respiratory motion. METHODS AND MATERIALS:
      In taking advantage of object-oriented programming, we implemented 4D Monte Carlo
      dose calculation. Local dose depositions in the patient are calculated while beam
      configuration and organ positions are changed continuously. Deformable image
      registration is used to describe the CT voxel displacement over time. RESULTS:
      The 4D Monte Carlo technique is applied to a lung cancer case planned for proton
      therapy. We show that the effect of motion on the dose distribution can be
      simulated effectively based on statistical motion parameterizations acting on the
      geometry or based on patient-specific 4D CT information. CONCLUSION: We present a
      novel method able to calculate dose with underlying time-dependent geometry. The
      technique allows 4D dose calculation in arbitrary time scales in a single
      simulation even for double-dynamic systems (e.g., time-dependent beam delivery
      under organ motion).

PMID- 15465214
TI  - Correlation between the respiratory waveform measured using a respiratory sensor
      and 3D tumor motion in gated radiotherapy.
AB  - PURPOSE: The purpose of this study is to investigate the correlation between the
      respiratory waveform measured using a respiratory sensor and three-dimensional
      (3D) tumor motion. METHODS AND MATERIALS: A laser displacement sensor (LDS:
      KEYENCE LB-300) that measures distance using infrared light was used as the
      respiratory sensor. This was placed such that the focus was in an area around the
      patient's navel. When the distance from the LDS to the body surface changes as
      the patient breathes, the displacement is detected as a respiratory waveform. To
      obtain the 3D tumor motion, a biplane digital radiography unit was used. For the
      tumor in the lung, liver, and esophagus of 26 patients, the waveform was compared
      with the 3D tumor motion. The relationship between the respiratory waveform and
      the 3D tumor motion was analyzed by means of the Fourier transform and a cross
      correlation function. RESULTS: The respiratory waveform cycle agreed with that of
      the cranial-caudal and dorsal-ventral tumor motion. A phase shift observed
      between the respiratory waveform and the 3D tumor motion was principally in the
      range 0.0 to 0.3 s, regardless of the organ being measured, which means that the
      respiratory waveform does not always express the 3D tumor motion with fidelity.
      For this reason, the standard deviation of the tumor position in the expiration
      phase, as indicated by the respiratory waveform, was derived, which should be
      helpful in suggesting the internal margin required in the case of respiratory
      gated radiotherapy. CONCLUSION: Although obtained from only a few breathing
      cycles for each patient, the correlation between the respiratory waveform and the
      3D tumor motion was evident in this study. If this relationship is analyzed
      carefully and an internal margin is applied, the accuracy and convenience of
      respiratory gated radiotherapy could be improved by use of the respiratory
      sensor.Thus, it is expected that this procedure will come into wider use.

PMID- 15465215
TI  - A dynamic supraclavicular field-matching technique for head-and-neck cancer
      patients treated with IMRT.
AB  - PURPOSE: The conventional single-isocenter and half-beam (SIHB) technique for
      matching supraclavicular fields with head-and-neck (HN) intensity-modulated
      radiotherapy (IMRT) fields is subject to substantial dose inhomogeneities from
      imperfect accelerator jaw/MLC calibration. It also limits the isocenter location
      and restricts the useful field size for IMRT. We propose a dynamic field-matching
      technique to overcome these limitations. METHODS AND MATERIALS: The proposed
      dynamic field-matching technique makes use of wedge junctions for the abutment of
      supraclavicular and HN IMRT fields. The supraclavicular field was shaped with a
      multileaf collimator (MLC), which was orientated such that the leaves traveled
      along the superoinferior direction. The leaves that defined the superior field
      border moved continuously during treatment from 1.5 cm below to 1.5 cm above the
      conventional match line to generate a 3-cm-wide wedge-shaped junction. The HN
      IMRT fields were optimized by taking into account the dose contribution from the
      supraclavicular field to the junction area, which generates a complementary wedge
      to produce a smooth junction in the abutment region. This technique was evaluated
      on a polystyrene phantom and 10 HN cancer patients. Treatment plans were
      generated for the phantom and the 10 patients. Dose profiles across the abutment
      region were measured in the phantom on films. For patient plans, dose profiles
      that passed through the center of the neck lymph nodes were calculated using the
      proposed technique and the SIHB technique, and dose uniformity in the abutment
      region was compared. Field mismatches of +/- 1 mm and +/- 2 mm because of
      imperfect jaw/MLC calibration were simulated, and the resulting dose
      inhomogeneities were studied for the two techniques with film measurements and
      patient plans. Three-dimensional volumetric doses were analyzed, and equivalent
      uniform doses (EUD) were computed. The effect of field mismatches on EUD was
      compared for the two match techniques. RESULTS: For a perfect jaw/MLC
      calibration, dose profiles for the 10 patients in the 3-cm match zone had an
      average inhomogeneity range of -1.6% to +1.6% using the dynamic-matching
      technique and -3.7% to +3.8% according to the SIHB technique. Measurements showed
      that dose inhomogeneities that resulted from 1-mm and 2-mm jaw/MLC calibration
      errors were reduced from as large as 27% and 45% with the SIHB technique to less
      than 2% and 5.7% with the dynamic technique, respectively. For -1-mm, -2-mm, +1
      mm, and +2-mm jaw/MLC calibration errors, respectively, treatment plans for the
      10 patients yielded average dose inhomogeneities of -5.9%, -3.0%, +2.7%, and
      +5.8% with the dynamic technique as compared to -22.8%, -11.1%, +9.8%, and +22.1%
      with the SIHB technique. Calculation based on a dose-volume histogram (DVH)
      showed that the SIHB technique resulted in larger changes in EUD of the PTV in
      the junction area than did the dynamic technique. CONCLUSION: Compared with the
      conventional SIHB technique, the dynamic field-matching technique provides
      superior dose homogeneity in the abutment region between the supraclavicular and
      HN IMRT fields. The dynamic feathering mechanism substantially reduces dose
      inhomogeneities that result from imperfect jaw/MLC calibration. In addition,
      isocenter location in the dynamic field-matching technique can be chosen for
      reproducible patient setup and for adequate IMRT field size rather than being
      dictated by the match position. It also allows angling of the supraclavicular
      field to reduce the volume of healthy lung irradiated, which is impractical with
      the SIHB technique. In principle, this technique should be applicable to any
      treatment site that requires the abutment of static and intensity-modulated
      fields.

PMID- 15465216
TI  - Automated model-based organ delineation for radiotherapy planning in prostatic
      region.
AB  - PURPOSE: Organ delineation is one of the most tedious and time-consuming parts of
      radiotherapy planning. It is usually performed by manual contouring in two
      dimensional slices using simple drawing tools, and it may take several hours to
      delineate all structures of interest in a three-dimensional (3D) data set used
      for planning. In this paper, a 3D model-based approach to automated organ
      delineation is introduced that allows for a significant reduction of the time
      required for contouring. METHODS AND MATERIALS: The presented method is based on
      an adaptation of 3D deformable surface models to the boundaries of the anatomic
      structures of interest. The adaptation is based on a tradeoff between
      deformations of the model induced by its attraction to certain image features and
      the shape integrity of the model. To make the concept clinically feasible,
      interactive tools are introduced that allow quick correction in problematic areas
      in which the automated model adaptation may fail. A feasibility study with 40
      clinical data sets was done for the male pelvic area, in which the risk organs
      (bladder, rectum, and femoral heads) were segmented by automatically adapting the
      corresponding organ models. RESULTS: In several cases of the validation study,
      minor user interaction was required. Nevertheless, a statistically significant
      reduction in the time required compared with manual organ contouring was
      achieved. The results of the validation study showed that the presented model
      based approach is accurate (1.0-1.7 mm mean error) for the tested anatomic
      structures. CONCLUSION: A framework for organ delineation in radiotherapy
      planning is presented, including automated 3D model-based segmentation, as well
      as tools for interactive corrections. We demonstrated that the proposed approach
      is significantly more efficient than manual contouring in two-dimensional slices.

PMID- 15465217
TI  - SIFT: a method to verify the IMRT fluence delivered during patient treatment
      using an electronic portal imaging device.
AB  - PURPOSE: Radiotherapy patients are increasingly treated with intensity-modulated
      radiotherapy (IMRT) and high tumor doses. As part of our quality control program
      to ensure accurate dose delivery, a new method was investigated that enables the
      verification of the IMRT fluence delivered during patient treatment using an
      electronic portal imaging device (EPID), irrespective of changes in patient
      geometry. METHODS AND MATERIALS: Each IMRT treatment field is split into a static
      field and a modulated field, which are delivered in sequence. Images are acquired
      for both fields using an EPID. The portal dose image obtained for the static
      field is used to determine changes in patient geometry between the planning CT
      scan and the time of treatment delivery. With knowledge of these changes, the
      delivered IMRT fluence can be verified using the portal dose image of the
      modulated field. This method, called split IMRT field technique (SIFT), was
      validated first for several phantom geometries, followed by clinical
      implementation for a number of patients treated with IMRT. RESULTS: The split
      IMRT field technique allows for an accurate verification of the delivered IMRT
      fluence (generally within 1% [standard deviation]), even if large interfraction
      changes in patient geometry occur. For interfraction radiological path length
      changes of 10 cm, deliberately introduced errors in the delivered fluence could
      still be detected to within 1% accuracy. Application of SIFT requires only a
      minor increase in treatment time relative to the standard IMRT delivery.
      CONCLUSIONS: A new technique to verify the delivered IMRT fluence from EPID
      images, which is independent of changes in the patient geometry, has been
      developed. SIFT has been clinically implemented for daily verification of IMRT
      treatment delivery.

PMID- 15465218
TI  - A multileaf collimator phantom for the quality assurance of radiation therapy
      planning systems and CT simulators.
AB  - PURPOSE: The evolution of three-dimensional conformal radiation treatment has led
      to the use of multileaf collimators (MLCs) in intensity-modulated radiation
      therapy (IMRT) and other treatment techniques to increase the conformity of the
      dose distribution. A new quality assurance (QA) phantom has been designed to
      check the handling of MLC settings in treatment planning and delivery. METHODS
      AND MATERIALS: The phantom consists of a Perspex block with stepped edges that
      can be rotated in all planes. The design allows for the assessment of several MLC
      and micro-MLC types from various manufacturers, and is therefore applicable to
      most radiation therapy institutions employing MLCs. The phantom is computed
      tomography (CT) scanned as is a patient, and QA assessments can be made of field
      edge display for a variety of shapes and orientations on both radiation treatment
      planning systems (RTPS) and computed tomography simulators. RESULTS: The
      dimensions of the phantom were verified to be physically correct within an
      uncertainty range of 0-0.7 mm. Errors in leaf position larger than 1 mm were
      easily identified by multiple observers. CONCLUSIONS: The MLC geometry phantom is
      a useful tool in the QA of radiation therapy with application to RTPS, CT
      simulators, and virtual simulation packages with MLC display capabilities.

PMID- 15465219
TI  - New data on the value of alpha/beta--evidence mounts that it is low.

PMID- 15465220
TI  - In regard to Vordermark et al. (Int J Radiat Oncol Biol Phys 2004;58:1242-1250).

PMID- 15465222
TI  - In regard to Paulino and Johnstone: Use of PET and CT imaging data in radiation
      therapy planning. Int J Radit Oncol Biol Phys 2004;59:4-5.

PMID- 15465225
TI  - A history of hand surgery in New York City.
AB  - The origins of Hand Surgery in New York City are temporally centered around World
      War II. Arthur J. Barsky, MD, Condict W. Cutler, Jr, MD and Emanuel B. Kaplan, MD
      laid the groundwork for our regional specialty prior to the War. J. William
      Littler, MD, Robert E. Carroll, MD, served in the Armed Forces and were
      instrumental in the development of the specialty in the second half of the 20th
      century. Hand services evolved in each of the major academic centers in New York
      including those led by Lee Ramsey Straub, MD, at the Hospital for Special
      Surgery, Richard J. Smith, MD at the Hospital for Joint Disease, Robert W.
      Beasley, MD at New York University and Berish Strauch, MD, and Morton Spinner,
      MD, at Albert Einstein and Montefiore. Several surgeons who worked with or were
      trained by these masters formed the nucleus of the next generation of leaders
      including Richard G. Eaton, MD, Martin A. Posner, MD, Harold M. Dick, MD, and
      Charles Melone, MD. Their proteges and a relatively small number of surgeons
      trained elsewhere, like Andrew J. Weiland, MD, and Robert Hotchkiss, MD, make up
      the current leadership of Hand Surgery in New York City.

PMID- 15465226
TI  - Long-term assessment of Swanson implant arthroplasty in the proximal
      interphalangeal joint of the hand.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical results of
      Swanson silicone implant arthroplasty of the proximal interphalangeal (PIP)
      joint, specifically evaluating clinical results with long-term assessment.
      METHODS: A retrospective review of 70 silicone implants of the PIP joint in 48
      patients was performed with an average follow-up period of 6.5 years (range, 3-20
      y). Clinical assessment included motion, stability, and alignment. Radiographic
      assessment included implant fracture, deformity, and cystic bone resorption. The
      pathology consisted of degenerative joint disease in 14, posttraumatic arthritis
      (TA) in 11, rheumatoid arthritis (RA) in 13, and idiopathic arthritis (IA)
      associated with collagen disease in 12 patients. Swan neck and boutonniere
      deformities were assessed separately. Statistical analysis of preoperative risk
      factors was compared with the postoperative assessment of pain, motion, and
      function (return to work). RESULTS: There was no significant change in the active
      range of motion (ROM) before and after PIP arthroplasty (26 degrees vs 30 degrees
      ). Correction of swan neck and boutonniere deformities was difficult, usually
      leading to poor results. There was improvement in maximum active extension before
      surgery lacking 32 degrees to after surgery lacking 18 degrees . From a
      statistical standpoint rheumatoid joint involvement with PIP arthroplasty had
      poorer results than degenerative or posttraumatic arthritis with respect to pain
      relief and ROM. Pain relief was present in 70% of replaced PIP joints with
      residual pain and loss of strength in 30%. Radiographic analysis showed abnormal
      bone formation (cystic changes) in 45%. There were 11 implant fractures and 9
      joints that required revision surgery. CONCLUSIONS: Silicone replacement of the
      PIP joint is effective in providing relief of pain from arthritis but does not
      provide improvement in motion or correction of deformity. It provided a poorer
      outcome in rheumatoid disease in comparison with degenerative, posttraumatic, or
      idiopathic arthritis.

PMID- 15465227
TI  - Metacarpophalangeal joint mechanics after 3 different silicone arthroplasties.
AB  - PURPOSE: This study was performed to compare metacarpophalangeal (MCP) joint
      mechanics after arthroplasty with 3 currently available silicone implants and to
      determine how postarthroplasty mechanics compares with the mechanics of the
      intact joint. METHODS: Planar 2-dimensional kinematic analysis was performed
      using digitized radiographs on 10 isolated fingers harvested from 5 fresh-frozen
      human cadavers. Radiopaque markers were affixed to the metacarpals and proximal
      phalanges, sewn to the flexor and extensor tendons, and placed into the stems and
      hinges of the implants. Each finger was tested intact, and after MCP joint
      replacement with 3 implants (Swanson [Wright Medical, Memphis, TN], Avanta
      [Avanta Orthopaedics, San Diego, CA], and NeuFlex [DePuy Orthopaedics, Warsaw,
      IN]). The fingers were secured to the test fixture and the flexor digitorum
      profundus flexor and extensor tendons were loaded with physiologic weights.
      Lateral radiographs were taken at approximately 10 degrees intervals and were
      digitized on a high-resolution scanner. Instantaneous center of rotation (ICR),
      tendon excursion, and tendon moment arm were calculated. Statistical analysis was
      performed using repeated measures one-way analysis of variance and Dunnett post
      tests. RESULTS: The ICRs of the intact and implanted MCPs did not follow a smooth
      path. The variability of the ICRs of the intact MCP joints was 2.1 +/- 0.8 mm.
      The variations in the Avanta and DePuy implants were similar (3.1 +/- 1.0 mm and
      3.5 +/- 1.5 mm, respectively), whereas the Swanson implant was higher (4.9 +/-
      1.7 mm). Implant pistoning was most pronounced with the Swanson implant, which
      moved 2.40 +/- 0.97 mm over the full range of motion. The Avanta and DePuy
      implants pistoned significantly less than the Swanson implant (1.05 +/- 0.45 mm
      and 0.69 +/- 0.31 mm, respectively). Flexor tendon excursion was greater for the
      intact joint when compared with all 3 implants while extensor tendon excursion
      was similar for all. Flexor tendon moment arm was similar for the intact joint
      and the Avanta and NeuFlex implants whereas the Swanson implant was reduced
      significantly; extensor tendon moment arms were similar for all. CONCLUSIONS: The
      ICR of the NeuFlex implant most closely matched that of the intact MCP joint. The
      Swanson implant had greater pistoning and dorsal-volar translation when compared
      with the intact joint and the Avanta and NeuFlex implants. The block-hinge type
      design of the Avanta and NeuFlex implants improved tendon moment arm overall when
      compared with the Swanson, likely imparting greater functional ability for finger
      motion. Overall the NeuFlex implant most closely matched the ICR, tendon
      excursion, and moment arm when compared with the intact native MCP joint.

PMID- 15465228
TI  - Functional outcome after surgery for Dupuytren's contracture: a prospective
      study.
AB  - PURPOSE: The purpose of this study was to assess the functional outcome after
      surgery for Dupuytren's contracture and the correlation between the change in the
      degree of deformity of the metacarpophalangeal joint (MCPJ) and the proximal
      interphalangeal joint (PIPJ) and the change in hand function. METHODS: Hand
      function in 30 patients was assessed by Sollerman hand function tests
      prospectively both before surgery and at 6 and 12 months after surgery. The
      deformity at the MCPJ and PIPJ was measured in degrees of angulation. The results
      were analyzed using the Spearman rank correlation test. In patients with multiple
      finger involvement the data were analyzed twice: first by using the measurements
      for the finger with the worst deformity and then repeating the analysis after the
      mean deformity was calculated. RESULTS: The mean preoperative MCPJ and PIPJ
      deformity was 31 degrees (range, 30 degrees to 76 degrees ) and 35 degrees
      (range, 30 degrees to 96 degrees ), respectively. The mean correction at the MCPJ
      and PIPJ was 19.6 degrees and 16 degrees , respectively. The mean preoperative
      Sollerman score was 72.8, which improved to 77.9 at 12 months after surgery.
      There was a statistically significant correlation between the total correction,
      PIPJ correction, and hand function at 6 and 12 months, but not with MCPJ
      correction. In those patients with multiple finger involvement these correlations
      remained true regardless of whether the mean or greatest deformity was
      considered. CONCLUSIONS: We conclude that improvement in deformity in Dupuytren's
      contracture leads to an improvement in hand function and that an improvement in
      the PIPJ contracture has a greater correlation with hand function than an
      improvement in the MCPJ contracture.

PMID- 15465229
TI  - Expression of bone morphogenetic proteins by Dupuytren's fibroblasts.
AB  - PURPOSE: Dupuytren's fibroblasts, or myofibroblasts, are the primary cell type in
      Dupuytren's disease. Growth factors play a role in the differentiation of
      fibroblasts to myofibroblasts. Myofibroblasts are specialized fibroblasts that
      display morphologic and biochemical features similar to smooth muscle cells.
      Cytokines, adhesion molecules, and extracellular matrix components are all
      thought to play a role in myofibroblast transdifferentiation. Recent research has
      shown that specific cytokines, such as transforming growth factor beta1 (TGF
      beta1), can modulate myofibroblast expression. We hypothesize that bone
      morphogenetic proteins (BMPs) play a role in the modulation of Dupuytren's
      fibroblasts. METHODS: Dupuytren's fibroblasts and normal palmar fascia
      fibroblasts (control) were analyzed for messenger RNA expression of BMPs (BMP-1, 
      2, -3, -4, -5, -6, -7, -8, -9, -10 and -11), their receptors (BMPR-IA, BMPR-IB,
      and BMPR-II), and their antagonists (follistatin and noggin) by reverse
      transcription polymerase chain reaction (PCR). Western blot analysis and
      immunostaining also were used to confirm the differential expression of BMP-4.
      RESULTS: With reverse-transcription PCR the expression profile for normal palmar
      fascia fibroblasts versus Dupuytren's fibroblasts was found to show similar
      expression of BMP-1 and -11; qualitatively decreased expression of BMP-6, BMP-8,
      BMPR-IA, BMPR-IB, and BMPR-II in Dupuytren's fibroblasts; and no expression of
      BMP-4 in Dupuytren's fibroblasts. There was no expression of BMP-2, -3, -5, -7, 
      9, and -10 in both the control fibroblasts and Dupuytren's fibroblasts. In line
      with the messenger RNA expression pattern BMP-4 was detected in only the control
      fibroblasts and not in the Dupuytren's fibroblasts, whereas BMP-8 (chosen for
      comparison purposes) was detectable in both cell populations. Immunostaining for
      BMP-8 and BMP-4 confirmed our findings with reverse-transcription PCR and Western
      blot analysis. CONCLUSIONS: This study reports on the expression of BMPs in
      Dupuytren's fibroblasts. We characterized the expression of BMPs in both normal
      palmar fascia fibroblasts and in Dupuytren's fibroblasts through reverse
      transcription PCR, Western blot analysis, and immunostaining. The most
      significant difference in expression profiles was in the expression of BMP-4;
      that is, BMP-4 was expressed in the normal fibroblasts but not in the Dupuytren's
      fibroblasts. Whether BMP-4 is necessary and/or sufficient for maintaining a
      normal palmar fascia fibroblast phenotype is not yet known. Further studies are
      needed to elucidate the exact role of BMPs, and especially BMP-4, in Dupuytren's
      fibroblasts.

PMID- 15465230
TI  - Augmented external fixation versus percutaneous pinning and casting for unstable
      fractures of the distal radius--a prospective randomized trial.
AB  - PURPOSE: Many outcome studies of various surgical techniques for unstable
      fractures of the distal radius have been published but applicability of the
      results remains limited because the majority of these trials were not done in a
      prospective and/or randomized manner. In this study we evaluated 2 common
      surgical techniques used in the treatment of unstable distal radius fractures in
      a randomized prospective fashion with a 1-year radiographic and clinical follow
      up period. Our hypothesis was that external fixation with augmentation would
      provide superior results compared with percutaneous pinning and casting. METHODS:
      Fifty patients younger than 65 years of age with unstable fractures of the distal
      radius were randomized into 1 of 2 surgical treatment groups: percutaneous pins
      with casting or augmented external fixation. All surgery was performed by 1 of 3
      surgeons within 10 days of injury. Over 80% of the fractures were classified as
      AO-ASIF C2 or C3 and there was a similar distribution of fracture types in each
      group. RESULTS: The use of augmented external fixation did not improve the mean
      radiographic parameters of radial length, radial angulation, or volar tilt.
      Restoration of volar tilt of highly comminuted fractures was difficult to achieve
      regardless of the technique. Improved articular surface reduction was realized
      with the use of an external fixator but overall only 3 patients were noted to
      have steps or gaps greater than 2 mm. No significant differences in mean
      Disabilities of the Arm, Shoulder, and Hand scores, total range of motion, grip
      strength, or health-related quality of life were observed between the groups. All
      3 patients diagnosed with sympathetic dystrophy had had external fixation.
      CONCLUSIONS: Although augmented external fixation represents a popular first line
      treatment for unstable fractures of the distal radius this study suggests that
      for fractures with minimal articular displacement similar clinical results can be
      obtained with percutaneous pinning and casting.

PMID- 15465231
TI  - Corrective osteotomy of malunited distal radius fractures using carbonated
      hydroxyapatite as an alternative to autogenous bone grafting.
AB  - PURPOSE: The purpose of the present study was to report on the author's
      experience using carbonated hydroxyapatite as a bony substitute in distal radius
      corrective osteotomies. METHODS: Six patients had a corrective osteotomy for a
      malunited distal radius fracture using carbonated hydroxyapatite as an
      alternative to an autogenous bone graft. Internal fixation of the osteotomy was
      achieved by using 2 or 3 K-wires. RESULTS: At an average follow-up evaluation of
      33 months (range, 22-45 mo) all the osteotomies united. Wrist flexion-extension
      motion improved from 75 degrees to 110 degrees , forearm rotation increased from
      116 degrees to 157 degrees , and grip strength had an average increase of 140% at
      the time of the final follow-up evaluation. All patients were satisfied and there
      were no reports of persistent pain. Radiographic evaluation showed an average
      volar tilt improvement from a preoperative dorsal angulation shifting into a
      neutral position in the sagittal plane; radial lengthening improved from an
      average of 4 mm (range, 2-6 mm) before surgery to 7 mm (range, 5-9 mm) after
      surgery, ulnar plus deformity improved by 5 mm. Radiographically the carbonated
      hydroxyapatite material was integrated completely into the bone tissue with
      evidence of progressive re-absorption and bony calcification over time. The Mayo
      wrist score system, according to Cooney and Krimmer modifications, improved by an
      average of 88 and 98 points (0-100 points), respectively. CONCLUSIONS: On the
      basis of this preliminary experience it is reasonable to consider carbonated
      hydroxyapatite as a viable alternative to bone grafting in conjunction with
      surgical correction of a distal radius malunion. It must be augmented, however,
      with internal fixation.

PMID- 15465232
TI  - Ulnar variance and subchondral bone mineralization patterns in the distal
      articular surface of the radius.
AB  - PURPOSE: Based on biomechanical experiments in specimens it is accepted widely
      that ulnar length determines loading of distal articular surface of the radius
      with ulna-minus variance increasing and ulna-plus variance decreasing the loading
      of the lunate compartment. Nevertheless a direct assessment of the actual loading
      conditions in the living is currently impossible. The aim of the present study is
      therefore to evaluate subchondral bone mineralization patterns to provide further
      information about the role of ulnar length in load transmission through the
      radiocarpal joint. METHODS: Twelve wrists of healthy subjects with an average age
      of 33 years and an average congenital ulna-minus wrist of -2.8 mm (range, -4 to 
      1 mm) were examined by means of computed tomography-osteoabsorptiometry. A
      further 5 wrists in healthy subjects with an average age of 52 years and an
      average congenital ulna-plus variance of +3.0 mm (range, +2 to +4 mm) were
      examined with the same technique. Seventeen wrist joints of 9 healthy subjects
      with ulna-zero variance were examined in the control group. RESULTS: The results
      show a mainly lunate mineralization pattern in subjects with ulna-minus wrists in
      75% of the cases, which is more frequent than in subjects with ulna-zero wrists.
      The results in ulna-plus variance show a mainly scaphoid mineralization pattern
      in 100% of cases. The differences in mineralization patterns are statistically
      significant. CONCLUSIONS: We conclude from these morphologic results in living
      subjects that ulnar length determines the peak mineralization patterns of the
      distal articular surface of the radius with a relatively lesser loading of the
      lunate fossa in ulna-plus variance and a relatively higher loading history in
      most cases of ulna-minus variance. The hypothesis, however, that ulna-minus
      variance is always a sign of a relatively higher loading history of the lunate
      fossa cannot be supported.

PMID- 15465233
TI  - A cadaver model to evaluate the accuracy and reproducibility of plain radiograph
      step and gap measurements for intra-articular fracture of the distal radius.
AB  - PURPOSE: The purpose of this study was to determine the accuracy and
      reproducibility of intra-articular step-off and gap displacements measured on
      plain radiographs using a standard cadaver model. METHODS: Twenty-two physicians,
      in a blinded randomized fashion using a standard technique, examined the
      radiographs of 12 unique combinations of step and gap displacement created by a 3
      part intra-articular osteotomy of the distal radius. Observer accuracy, inter-
      and intraobserver agreement, and tolerance limits were calculated. RESULTS: The
      results of this study suggest that observers, independent of skill level, may
      measure step-off and gap displacements accurately to within .62 +/- .53 mm (95%
      confidence interval = .59-65). The accuracy of measurement was influenced by the
      quality of the radiograph. Intraclass correlation coefficient scores showed
      "substantial" (.78) to "almost perfect" (.81) inter- and intraobserver agreement.
      CONCLUSIONS: These data can aid in the interpretation of clinical studies of
      acute distal radius fractures that are based on plain radiography.

PMID- 15465234
TI  - A survey of the surgical management of acute and chronic scapholunate
      instability.
AB  - PURPOSE: Scapholunate instability is a challenging problem and controversy
      persists among hand surgeons with respect to treatment choice. The purpose of
      this study was to evaluate the pattern of practice among specialized hand
      surgeons in the management of both acute and chronic scapholunate instability.
      METHODS: A mailed survey study was sent to the 1,628 members of the American and
      Canadian Societies for Surgery of the Hand. Hand surgeons were asked to complete
      a comprehensive management questionnaire that examined a surgeon's treatment
      algorithm in the clinical case of acute and chronic scapholunate instability. The
      algorithm included the choices of further investigation, timing of surgery,
      surgical approach, surgical procedure, fixation, and predicted outcome. RESULTS:
      Of the 468 hand surgeons who responded to the survey the vast majority elected to
      perform surgery when confronted with a case of scapholunate instability. Early
      surgical intervention within 6 weeks of injury using an open dorsal approach was
      favored in both acute and chronic cases. The preferred surgical procedure in the
      acute case was scapholunate repair combined with a capsulodesis followed by
      scapholunate ligament repair alone. Favored management of the chronic case
      included Blatt capsulodesis alone, capsulodesis combined with a scapholunate
      ligament repair, or scaphotrapezium-trapezoid arthrodesis. A majority of surgeons
      used K-wire fixation, especially of the scapholunate and scaphocapitate in both
      acute and chronic cases. CONCLUSIONS: This survey confirms a consensus for the
      early soft tissue surgical management of acute scapholunate instability using a
      scapholunate ligament repair with or without a capsulodesis. The management of
      chronic scapholunate instability is highly variable among respondents and the
      choice of either a soft tissue or bony procedure may depend to a large extent on
      intraoperative findings.

PMID- 15465235
TI  - Carpal canal pressure of the distracted wrist.
AB  - PURPOSE: This study was conducted to study the effect of distraction across the
      wrist joint on carpal canal pressure. METHODS: Ten cadaver specimens were mounted
      vertically in neutral forearm rotation by 2 half pins that transfixed the radius
      and ulna. The wrist joint was distracted by suspending weights from the middle
      finger. A balloon-tipped catheter, percutaneously introduced into the carpal
      canal and connected to a transducer, was used to measure carpal canal pressure.
      The carpal canal pressure was measured at 0 to 4.54 kg of distraction in 0.45-kg
      increments and at 6.81 kg and 9.08 kg of distraction. Three wrist positions were
      tested: neutral, 30 degrees of flexion, and 30 degrees of extension. RESULTS:
      Highly linear direct relationships between wrist distraction force and carpal
      canal pressure over baseline were observed in all positions of the wrist.
      Statistically significant increases in carpal canal pressure over baseline were
      observed at a wrist distraction force of 2.27 kg or more with the wrist in
      neutral position, at 1.82 kg or more with the wrist in 30 degrees of extension,
      and at 4.09 kg or more with the wrist in 30 degrees of flexion. At each level of
      wrist distraction force of 3.63 kg or less the carpal canal pressure of the
      extended wrist was significantly higher than that of the wrist in neutral
      position. At each level of wrist distraction force 4.54 kg or less the carpal
      canal pressure of the extended wrist was significantly higher than that of the
      flexed wrist. No statistically significant differences were observed at any level
      of wrist distraction force between carpal canal pressures in the neutral and
      flexed positions of the wrist. CONCLUSIONS: Distraction across the wrist joint
      causes a statistically significant highly linear increase in carpal canal
      pressure. The position of the distracted wrist also has a considerable effect on
      carpal canal pressure, with the extended position associated with the largest
      increases in carpal canal pressure and the flexed position with the smallest
      increases in carpal canal pressure.

PMID- 15465236
TI  - The accuracy of distal posterior interosseous and anterior interosseous nerve
      injection.
AB  - PURPOSE: To standardize a technique of delivering a local anesthetic to the
      posterior interosseous nerve (PIN) and anterior interosseous nerve (AIN) by using
      the anatomic landmarks of the wrist and to evaluate the accuracy of the technique
      in a cadaver model. METHODS: Techniques for PIN and AIN injection and for PIN
      injection alone are described. Techniques were tested in a fresh frozen cadaver
      model by using methylene blue injections. Stained nerves were dissected under
      loupe magnification. Digital photographic images were taken of each nerve.
      Staining was quantified by calculating the mean density and area stained.
      RESULTS: For both techniques methylene blue was delivered accurately to the PIN
      in 100% of the samples. Methylene blue was delivered accurately to the AIN in
      100% of samples in which it was injected. CONCLUSIONS: These techniques saturated
      successfully the PIN and AIN and may be useful as diagnostic and therapeutic
      tools for chronic wrist pain and in evaluating presurgically the effectiveness of
      partial wrist denervation.

PMID- 15465237
TI  - The long ulnar sliding osteotomy.
AB  - This study presents a modified technique for performing ulnar shortening
      osteotomies. The long ulnar sliding osteotomy differs from standard ulnar
      shortening techniques in 2 ways: (1) a single cut is made in the ulna and (2)
      screws only are used for fixation.

PMID- 15465238
TI  - The effect of partial A2 pulley excision on gliding resistance and pulley
      strength in vitro.
AB  - PURPOSE: The purpose of this study was to investigate the effect of partial
      excision of the A2 pulley on the gliding resistance and the strength of the
      residual pulleys in a human in vitro model with or without tendon repair.
      METHODS: We used 32 cadaveric human fingers from 11 cadavers. The A2 pulley was
      excised successively 25%, 50%, and 75%, cutting either from the distal toward the
      proximal edge or from the proximal toward the distal edge. The peak gliding
      resistance between intact or repaired tendon and partially excised pulley was
      measured. After the gliding resistance test the pulley breaking strength and
      stiffness were measured. RESULTS: The peak gliding resistance exhibited the same
      statistical trends for the intact tendon and the repaired tendon groups. In the
      intact tendon groups the sequential excision of the A2 pulley from the distal
      toward the proximal edge had no significant effect on peak gliding resistance.
      With the A2 pulley cut from the proximal toward the distal edge, however, there
      was a significant increase in peak gliding resistance with 25% remaining pulley
      distally (0.82 N) compared with intact (0.42 N), 75% (0.57 N), and 50% (0.63 N)
      pulley remaining proximally. The 25% distal portion of the A2 pulley had a
      significantly higher breaking strength than the 25% proximal portion (160 N vs
      96.7 N, respectively). Similarly the stiffness was greater in the distal portion
      compared with the proximal portion (120 N/mm vs 70.5 N/mm). CONCLUSIONS: After A2
      pulley excision the size and location of the remaining pulley affects the
      resulting gliding resistance, stiffness, and failure strength. At the most
      extreme excision level tested the residual 25% distal segment of the pulley
      exhibited significantly greater peak gliding resistance compared with the 25%
      proximal segment, as well as greater strength and stiffness. If excision of the
      A2 pulley is limited to 50% (either proximally or distally), however, there is
      little increase in gliding resistance and the retained strength of the pulley is
      substantial. These data support the clinical practice of partial pulley excision,
      up to a limit of 50%, to facilitate exposure and tendon repair.

PMID- 15465239
TI  - Tendon healing in vitro: genetic modification of tenocytes with exogenous PDGF
      gene and promotion of collagen gene expression.
AB  - PURPOSE: Promotion of collagen production can increase tendon healing strength
      and reduce repair ruptures. Transfer of an exogenous growth factor gene to
      tenocytes of intrasynovial tendons may enhance the capacity of cells to produce
      collagen. We transferred the platelet-derived growth factor B (PDGF-B) gene to
      tenocytes and investigated its effects on the expression of the PDGF gene and the
      type I collagen gene in an in vitro tenocyte culture model. METHODS: Tenocytes
      obtained from explant cultures of rat intrasynovial tendons were treated for 12
      hours with the plasmid containing the PDGF complementary deoxyribonucleic acid
      (cDNA) with liposome and were then cultured for 6 additional days. The control
      tenocytes did not receive the exogenous gene and liposome. Efficiency of the gene
      transfer was evaluated by using reverse transcription polymerase chain reactions
      (RT-PCR) to detect the presence of the transferred gene in the tenocytes.
      Enhancement of the expression of the target gene was assessed by RT-PCR with
      primers effective to amplify both internal and transferred genes. Expression of
      the type I collagen gene was determined by quantitative analysis of the products
      of RT-PCR. RESULTS: Levels of expression of the type I collagen gene by tenocytes
      were increased significantly by transfer of the exogenous PDGF gene to the
      tenocytes. Efficiency of the gene transfer was confirmed by the presence of
      exogenous PDGF cDNA in the tenocytes receiving the transferred gene. Expression
      of the PDGF gene increased significantly in the cells treated with exogenous PDGF
      cDNA. CONCLUSIONS: Exogenous PDGF genes can be transferred effectively into
      intrasynovial tenocytes and the transfer increases significantly the expression
      of genes for PDGF and type I collagen. Transfer of the PDGF gene may offer a
      novel way of effectively promoting healing of intrasynovial flexor tendons. The
      findings warrant future in vivo study to test the effectiveness of gene therapy
      to promote flexor tendon healing.

PMID- 15465240
TI  - Locking repairs for obliquely cut tendons: Effects of suture purchase and
      directions of locking circles.
AB  - PURPOSE: Oblique cuts in tendons weaken conventional repairs but locking sutures
      improve the repair strength of the tendon. In this study we assessed how suture
      purchase and direction (or type) of locking sutures affect the repair strength.
      METHODS: Ninety-three fresh pig flexor tendons were transected obliquely (45
      degrees to the long axis of the tendon) and repaired with either a locking
      Kessler repair (with perpendicular or horizontal locking circles) or a locking
      cruciate method (with oblique locking or perpendicular locking circles). The
      suture purchase in the short side of the tendon stump with a perpendicular
      locking Kessler repair ranged from 0.3 to 1.2 cm. The gap formation and ultimate
      strength were measured to compare the biomechanical performance for each repair.
      RESULTS: The repair strength increased significantly as the suture purchase
      increased from 0.3 to 1.0 cm in oblique tendon lacerations, with a suture span of
      1.0 cm being the strongest. The strength decreased significantly when the span
      was 1.2 cm. The repairs with horizontal locking sutures were significantly weaker
      than those with perpendicular locking sutures. The locking cruciate repair with
      the perpendicular locking circles had strength identical to that of the cruciate
      with oblique locking circles. CONCLUSIONS: Both suture purchase and the direction
      of locking circles affect the repair strength remarkably. For locking repairs the
      suture purchase of 1.0 cm in an obliquely cut tendon produced the highest
      strength; the repairs with a purchase less than 0.4 cm had significantly reduced
      strength. The strength of the repairs with locking circles perpendicular to the
      long axis of the tendon was significantly greater than that of the repairs with
      locking circles parallel to the long axis of the tendon.

PMID- 15465241
TI  - The terminal tendon of the digital extensor mechanism: Part I, anatomic study.
AB  - PURPOSE: The purpose of this study was to examine the anatomy of the terminal
      tendon (TT) and its relationship to adjacent structures. MATERIALS: The extensor
      tendons of 56 cadaveric digits (52 fresh-frozen and 4 formalin-preserved)
      underwent anatomic dissection. RESULTS: The TT is a segment between the
      convergence of the lateral bands proximally and the bony insertion in the phalanx
      distally. The ulnar lateral bands were thicker than the radial bands. The average
      distance from the TT insertion to the germinal matrix of the nail bed was 1.4 mm.
      The triangular ligament (TL) is a thin layer of transverse fibers between the
      lateral bands proximal to the TT. The dimensions of the TT and the TL vary
      relative to the size of the digit with the largest often occurring in the middle,
      followed by the ring, index, and small finger. The transverse retinacular
      ligament (TRL) had a dorsal attachment to the lateral bands and was much more
      defined and distinct than the oblique retinacular ligament. The ulnar TRL often
      was thicker than the radial TRL. CONCLUSIONS: The TT is the primary structure
      responsible for extending the distal interphalangeal (DIP) joint. The function of
      the adjacent retinacular structures is to provide stability to the TT. The thin
      nature and proximity of the TT to the nail matrix must be kept in mind during
      surgery. Knowledge of the TT anatomy is necessary for further study of its
      kinematics and pathology and for diagnosis and management of its disorders.

PMID- 15465242
TI  - The terminal tendon of the digital extensor mechanism: Part II, kinematic study.
AB  - PURPOSE: To conduct kinematic analyses of both intact and sectioned terminal
      tendon (TT) of multiple fingers in the hand. METHODS: The TTs of 36 fresh-frozen
      cadaveric digits were used in this study. TT excursion was assessed along with
      the influence on proximal joint motion. The influence of TT lengthening and
      shortening on distal interphalangeal (DIP) joint motion were investigated.
      RESULTS: TT excursion averaged 1 mm at the DIP joint and was influenced by the
      proximal interphalangeal (PIP) joint but not the position of other joints in the
      hand and wrist. The greatest degree of DIP joint motion averaged 86 degrees when
      the PIP joint was in full flexion, whereas the least motion averaged 45 degrees
      when this joint was in neutral position. Lengthening of the TT resulted in
      angular deformity at the DIP joint. Average flexion deformities reached 25
      degrees at 1 mm, 36 degrees at 2 mm, 49 degrees at 3 mm, and 63 degrees at 4 mm
      of lengthening. The middle finger showed the greatest flexion deformity, followed
      by the ring, small, and index fingers. Shortening the TT by as little as 1 mm
      resulted in difficult tendon repair because of excessive tension and minimal or
      no DIP joint flexion was obtained. CONCLUSION: Only DIP and PIP joints affect TT
      excursion; hence these are the main joints to be immobilized to protect TT
      repair. The middle finger TT showed the least tolerance to lengthening with
      potential for mallet deformity. Joint flexion deformity is proportional to tendon
      lengthening. Only 1 mm of TT lengthening results in approximately 25 degrees of
      DIP joint extension lag, and 4 mm of TT lengthening results in DIP joint flexion
      deformity greater than 60 degrees . Even 1 mm of TT shortening will seriously
      restrict DIP joint flexion.

PMID- 15465243
TI  - Fiber length variability within the flexor carpi ulnaris and flexor carpi
      radialis muscles: implications for surgical tendon transfer.
AB  - PURPOSE: The purpose of this study was to understand the detailed architectural
      properties of the human flexor carpi radialis (FCR) and flexor carpi ulnaris
      (FCU) muscles and their implications for tendon transfer surgery. METHODS: Muscle
      fiber length was measured in 6 separate regions of the FCU and FCR from 10
      cadaveric specimens. Sarcomere length was measured by laser diffraction for
      normalization. Moment arms were estimated by measuring tendon excursion with
      respect to joint angle. The position of entry of the motor nerve branches into
      each muscle also was measured to establish limits for the safe length of muscle
      mobilization. RESULTS: Muscle fiber length varied significantly along both the
      FCU and FCR. Fiber length variability in the FCU was twice that of the FCR.
      Although the average fiber length for both muscles across all regions was similar
      (62.6 +/- 2.1 mm for the FCR and 63.1 +/- 4.0 mm for the FCU), the proximal
      fibers of the FCU were longer compared with the proximal fibers of the FCR and
      the distal fibers of the FCU were shorter compared with the distal fibers of the
      FCR. The 99% confidence interval for the second nerve branch entry into the
      muscles was located approximately 69 mm distal to the medial epicondyle for the
      FCU and approximately 73 mm distal for the FCR. CONCLUSIONS: These data show
      different designs of both the FCU and the FCR. The functional significance of
      fiber length variability is not clear but imply that, when used in tendon
      transfer, the properly mobilized FCU has a much greater excursion.

PMID- 15465244
TI  - A biomechanical modeling of injury, repair, and rehabilitation of ulnar
      collateral ligament injuries of the thumb.
AB  - PURPOSE: The use of early active motion protocols after repair of the thumb ulnar
      collateral ligament (UCL) theoretically could avoid the complications of
      postoperative immobilization and improve ligament healing. The goals of this
      study were as follows: (1) to develop an accurate model of acute UCL rupture, (2)
      to determine the strain pattern in the UCL during constrained active thumb motion
      in intact and repaired thumbs, and (3) to determine the load to failure and
      strain of the UCL during rupture in forced abduction. METHODS: Sixteen fresh
      frozen adult cadaver thumbs were mounted in a testing apparatus designed for
      testing the strain in the UCL during constrained active motion and abduction load
      to failure. Strain data for the UCL during motion were measured. Specimens were
      tested to failure using an MTS machine. Dynamic strain data were acquired
      throughout the loading cycle. Repair of the torn ligament was performed with a
      suture anchor technique. Strain and load-to-failure measurements then were
      repeated in the repaired specimens. Differences in the strain values and failure
      forces between the intact and repaired specimens then were compared. RESULTS: A
      reliable model of a UCL rupture was created. Strains in the UCL were similar
      during active motion in both intact and repaired specimens. A significant
      decrease in maximum load to failure was noted in repaired specimens but failure
      reliably occurred at strains 3 times greater than expected with active motion.
      CONCLUSIONS: A controlled active motion therapy protocol after suture anchor
      repair of a ruptured UCL of the thumb is safe from a biomechanical point of view.

PMID- 15465245
TI  - Irreducible volar subluxation of the metacarpophalangeal joint of the thumb.
AB  - An unusual case of irreducible volar metacarpophalangeal (MCP) joint subluxation
      of the thumb is described. The tendon of the extensor pollicis longus (EPL) was
      trapped palmar to the metacarpal head and open reduction was necessary.

PMID- 15465246
TI  - The treatment of an osteochondral shearing fracture-dislocation of the head of
      the proximal phalanx: a case report.
AB  - We report the morphology and treatment of a proximal interphalangeal joint
      dislocation resulting in an injury to the articular surface of the proximal
      phalanx and avulsion of the radial collateral ligament from its proximal origin.
      A large osteochondral fragment was sheared from the radial articular surface of
      the proximal phalanx and remained displaced volarly after reduction of the joint.
      Plain radiographs and 2- and 3-dimensional computed tomography images were used
      to evaluate this unusual injury before surgery. Open reduction and internal
      fixation using a small K-wire and figure-of-eight wire technique restored the
      articular surface of the head of the proximal phalanx and gave a satisfactory
      functional result.

PMID- 15465247
TI  - Free vascularized joint transfer from the nonreplantable digit as a free flap for
      primary reconstruction of complex hand injury.
AB  - We report our experience in treating a a patient with an electrical saw injury to
      the right hand that resulted in incomplete amputation of the ring and small
      fingers at the metacarpophalangeal (MCP) joint with segmental tissue loss. Ray
      amputation of the small finger was performed because of extensive tissue loss.
      The proximal interphalangeal joint of the nonreplantable small finger was
      transferred as a fillet flap for primary reconstruction of the severely damaged
      MCP joint of the ring finger after revascularization. Two years after surgery
      active range of motion of the reconstructed MCP joint was 35 degrees extension to
      85 degrees flexion with no instability or pain.

PMID- 15465248
TI  - Treatment of radial and ulnar artery pseudoaneurysms using percutaneous thrombin
      injection.
AB  - Pseudoaneurysm formation is a recognized complication of arterial catheterization
      or traumatic arterial disruption, which may lead to considerable morbidity.
      Ultrasound-guided thrombin injection has been shown to be effective in the
      treatment of peripheral pseudoaneurysms; however, its application in the
      management of radial or ulnar artery pseudoaneurysms has not been well
      established. Arterial thrombosis and distal embolization are concerns when
      treating a pseudoaneurysm involving a small vessel. We performed successful
      ultrasound-guided thrombin injection of a 3-cm radial artery and a 2.5-cm ulnar
      artery pseudoaneurysm resulting from arterial catheterization and missed arterial
      trauma, respectively. Radial artery recannalization occurred 28 days after the
      procedure whereas the ulnar artery remained patent throughout the observation
      period.

PMID- 15465249
TI  - The value of medical leeches in the treatment of class IIC ring avulsion
      injuries: report of 2 cases.
AB  - Ring avulsion injuries pose a serious problem for the hand surgeon. According to
      the severity of the injury several classifications and their modifications have
      been proposed. In class IIC ring avulsion injuries arterial circulation is intact
      but only the venous supply is disrupted. Several therapeutic approaches have been
      suggested for these types of injuries. We present two class IIC cases that were
      treated successfully solely with leeches, with excellent results. Although the
      method is not a substitute for microvascular intervention leeches can be used
      when the clinical condition of a patient does not permit a lengthy surgery and if
      microvascular techniques fail or are thought to be pointless.

PMID- 15465250
TI  - Relative slowing of the median antidromic sensory nerve conduction velocity to
      the ring finger in screening for carpal tunnel syndrome.
AB  - PURPOSE: This study analyzed the accuracy of the relative slowing of the
      antidromic sensory conduction velocity of the median nerve in comparison with the
      ulnar nerve, from the wrist to the ring finger, in the diagnosis of carpal tunnel
      syndrome (CTS). METHODS: Eighty-two patients had been referred consecutively to
      our department to confirm or exclude CTS. The antidromic sensory conduction
      velocities of the median nerve and the ulnar nerve from the wrist to the ring
      finger were determined. The difference between the 2 values was calculated to
      express the relative slowing of the median nerve compared with the ulnar nerve.
      Carpal tunnel syndrome was diagnosed when the patient had clinical symptoms
      compatible with CTS confirmed by an established electrophysiologic investigation.
      The accuracy of a relative slowing of 5 m/s, 10 m/s, and 15 m/s of the median
      antidromic sensory conduction velocity to the ring finger was determined to
      diagnose CTS. RESULTS: At a cut-off value of 5 m/s the sensitivity was 95%, the
      specificity was 63%, and the efficiency was 79%. At a cut-off value of 10 m/s the
      sensitivity was 90%, the specificity was 85%, and the efficiency was 88%. At a
      cut-off value of 15 m/s the sensitivity decreased to 83%, the specificity
      increased to 93%, and the efficiency was 88%. CONCLUSIONS: A high accuracy is
      achieved in the diagnosis of CTS by determining the relative slowing of the
      median antidromic sensory nerve conduction velocity from the wrist to the ring
      finger.

PMID- 15465251
TI  - Anatomic variation--a bony canal for the median nerve at the distal humerus: a
      case report.
AB  - We report a rare anatomic variation in which the median nerve travels in a bony
      canal of the distal humerus, separating from the brachial artery. We encountered
      this during neurolysis for posttraumatic median nerve palsy in a 10-year-old boy.
      We suggest that this anatomic variation was related strongly to this patient's
      median nerve palsy.

PMID- 15465252
TI  - Arthroscopic ganglionectomy?

PMID- 15465254
TI  - Anatomic tilt X-rays of the distal radius: an ex vivo analysis of surgical
      fixation.

PMID- 15465256
TI  - Basal joint osteoarthritis of the thumb: a prospective trial of steroid injection
      and splinting.

PMID- 15465258
TI  - [Case control study of extended-spectrum betalactamase producing Serratia
      marcescens outbreak in a paediatric intensive care unit].
AB  - OBJECTIVES: To identify patient-related risk factors of infection and ways of
      transmission of extended-spectrum betalactamase (ESBL) producing Serratia
      marcescens in the paediatric intensive care unit (PICU) of Amiens university
      hospital (France) between June and July 2002. METHODS: Five cases (four pulmonary
      infected and one stool contaminated symptom-free neonates) and 35 controls,
      admitted in the PICU, are included. S. marcescens ESBL analysed are isolated from
      respiratory tract and faecal samples for cases and urine and pus samples from two
      non-paediatric other patients. Univariate and multivariate analysis are performed
      on EPI INFO 6.04 dFr and SPSS 11.0.1. RESULTS: S. marcescens ESBL infections or
      colonisations rate is 12.5% [4.7-27.6]. The incidence is 8.8 [6.7-11.6] per 1000
      hospital-stay days. By univariate analysis, cases and controls don't differ with
      respect of age, sex, and weight at admission or preterm delivery. Cases don't
      have more often invasive nursing care than controls. But, they were intubated (P
      <0.03) and hospitalised (P <0.03) for a longer time than controls. Linear
      regression analysis showed that duration of intubation was independent predictor
      of acquisition of S. marcescens ESBL (P <0.008). S. marcescens ESBL strains
      implicated in pulmonary infections, showed the same pattern of multidrug
      resistant and ERIC-PCR profile. This clone differs from others isolated from
      stool or other samples from other hospital wards. CONCLUSION: As S. marcescens
      cross-colonization appears to be due to lake of hand hygiene and asepsis during
      invasive nursing care, reinforcing hygiene measures permit to contain the
      outbreak.

PMID- 15465259
TI  - [Contribution of urinary pneumococcal antigen detection combined with the
      research of legionella antigen for diagnosis of pneumonia in hospitalized
      patients].
AB  - AIM OF THE STUDY: Bacteriological confirmation of pneumonia (PNM) in hospitalized
      patients is often erratic or belated. Because of importance of prognosis, early
      adaptation of treatment requires an empirical antimicrobial therapy (generally
      aminopenicillin and macrolide combination). The starting therapeutic strategy
      should profit by a fast and reliable test asserting a pneumococcal etiology. The
      Binax Now S. pneumoniae (BNP) test allows an urinary pneumococcal antigen (UPA)
      detection using an immunochromatographic membrane assay within 15 minutes.
      MATERIALS AND METHODS: We first evaluated the BNP test for 28 patients with
      pneumococcal PNM proved by culture, and 118 negative control patients without
      PNM. The BNP test was then evaluated by testing urine from 158 hospitalized
      patients with a clinical picture of PNM (community-acquired: 90, nosocomial: 68)
      for whom a research of urinary Legionella antigen (Binax Now) was prescribed and
      was positive for only two cases. 57 patients (36.1%) were hospitalized in ICU.
      RESULTS: The sensitivity was 71.4% (85.7% for the 21 bacteriemic PNM), and the
      specificity was 98.3%; that is consistent with previous published data. Among the
      158 patients with PNM, UPA was detected in 17 cases (10.8%): 15 within the
      community-acquired PNM (16.7%) and 2 (2.9%) within the nosocomial cases. The
      pneumococcal etiology was confirmed by bacteriological samples in 7/17 patients
      (6 by blood cultures). The 10 others showed clinical and radiological features in
      agreement with a pneumococcal PNM. Among the 141 patients with negative AUP, S.
      pneumoniae was isolated from 6 of them (2 in blood cultures). CONCLUSION: The
      Binax Now S. pneumoniae test allowed a fast and reliable etiological diagnosis in
      10.8% of hospitalized PNM (16.7% of the community-acquired cases) having a
      research of urinary Legionella antigen (conceiving with severity factors). So it
      could conduce to an improved adjustment of the starting antimicrobial therapy of
      hospitalized adult patients with PNM.

PMID- 15465260
TI  - [Evaluation of Prolex for the rapid identification of streptococci isolated in
      medical microbiology].
AB  - The need to rapidly identify streptococci responsible for acute infectious
      diseases has led to the development of agglutination techniques that are able to
      identify streptococcal group antigens (A, B, C, D, F, and G) directly from
      primoculture colonies on blood agar. The Prolex agglutination tests (Pro-Lab
      Diagnostics, Richmond Hill, Ontario, Canada), distributed in France by i2a, have
      been used for the determination of group antigens of 166 isolates of streptococci
      and enterococci previously identified in the National Reference Center for
      Streptococci. The results obtained with the Prolex reagents have permitted to
      correctly identify all pyogenic beta-hemolytic streptococci (23 Streptococcus
      pyogenes, 21 Streptococcus agalactiae, 33 Streptococcus dysgalactiae subsp.
      equisimilis including 6 group C and 27 group G, and 5 Streptococcus porcinus
      including 4 group B). Four differences between unexpected agglutinations (A or F)
      and species identifications have been obtained. These differences were observed
      for four non-hemolytic isolates of Streptococcus mutans, Streptococcus gordonii,
      Streptococcus infantarius, and Streptococcus suis. The anti-D reagent has been of
      value as a marker for isolates of enterococci. Thus, these results confirm the
      abilities of these agglutination tests for the grouping of beta-hemolytic
      streptococci. Moreover, the use of Prolex has the advantage to be rapid because
      of the non-enzymatic but chemical extraction of streptococcal antigens.

PMID- 15465261
TI  - [Rapid antigen detection tests for diagnosis of group A streptococcal
      pharyngitis: comparative evaluation of sensitivity and practicability of 16 in
      vitro diagnostics medical devices performed in July 2002 by the French health
      products safety agency (Afssaps) as part of its market control mission].
AB  - Within the scope of its health products control mission, the French Health
      Products Safety Agency (Afssaps) collaborating with two expert's sites, has
      assessed the 16 tests available on the French market in 2002 for rapid diagnosis
      of the Streptococcus A tonsillitis. The purpose of this study was to verify the
      reliability and rapidity of these tests and to give some information to the users
      about their analytical criteria and practicability characteristics. The
      analytical study has been performed on a same panel of four reference strains of
      Streptococcus pyogenes dilutions to determine the limit of detection of all the
      reagents in the same condition of methodology. The limit of detection has been
      calculated with the results expressed in colony forming unit by ml (CFU/ml). The
      practicability study has permitted to analyze the quality of the presentation,
      the easiness of the final reading and of performing tests. A score has been
      established for each rapid test. A classification of the analytical sensitivity
      (limit of detection) and practicability (score) of these 16 devices has been
      established. The limit of detection of the reagents giving the best results
      allows the detection of the lowest bacterial concentration of the panel which is
      10(5) CFU/ml. Regarding practicability, the results suggest that, the
      immunochromatographic strip methods have the best score in a view with the use by
      a non medical laboratory.

PMID- 15465262
TI  - [Characterization of an extracellular protease from Clostridium difficile].
AB  - Clostridium difficile is an intestinal pathogen, which produces two main
      virulence factors, the exotoxins A and B. Other bacterial structures have been
      implicated in the colonization of the gastrointestinal tract, which is the first
      step of the pathogenic process. C. difficile expresses adherence factors and
      also, displays some surface-associated proteolytic activity, which could play a
      role in the physiopathology of this bacterium. The aim of this work was to study
      the protein named Cwp84 which displays significant homologies with many cysteine
      proteases. The coding catalytic domain of this protein has been cloned in the
      expression system pGEX-6P-1, as an in-frame fusion with the gluthatione S
      transferase, and subsequently purified. The purified fraction showed proteolytic
      activity on gelatine and BAPNA, but not on azocoll, suggesting a highly selective
      substrate specificity. The results obtained from inhibition experiments confirmed
      that Cwp84 belongs to the cysteine protease family. Cwp84 could play a role in
      degrading some specific host proteins or in the maturation of surface-associated
      bacterial proteins.

PMID- 15465263
TI  - [Heterogeneity of Brain Heart Infusion agar media (BHI): effects on the
      determination of the vancomycin and the teicoplanin minimal inhibitory
      concentrations (MIC) of Staphylococcus aureus strains].
AB  - The influence of BHI media commercially available on the results of glycopeptides
      MIC measured by E-test method was studied on 36 S. aureus isolates (21 MRSA and
      15 MSSA). The MIC obtained with the vancomycin and the teicoplanin determined by
      the E-test method, on the ready prepared BHI plates (AES) and the plate prepared
      at the laboratory among the four dehydrated bases (AES, Biorad, Oxoid, and Becton
      Dickinson), were compared. The mean of the MIC showed variations from 3.14
      (Biorad) to 5.25 mg/L (Oxoid) and from 3.33 (Biorad) to 9.75 mg/L (ready prepared
      AES) respectively for the vancomycin and for the teicoplanin. A variance analysis
      (Test de Friedman) showed a significant difference between the five media (p
      <0.001) with the two antibiotics. The comparison of media 2 by 2 allowed that all
      combinations excepted one (Biorad vs Becton with the vancomycin) were
      statistically different (p <0.001). The variation of the MIC observed in relation
      to the origin of the product of BHI media requires the inclusion of glycopeptide
      intermediate S. aureus reference strains to control the prepared culture media.

PMID- 15465264
TI  - [Two efflux systems expressed simultaneously in clinical Pseudomonas aeruginosa].
AB  - Active efflux systems MexAB-OprM and MexXY were found to be overexpressed
      simultaneously in 12 multiresistant clinical isolates of Pseudomonas aeruginosa.
      Nine of these strains (agrZ mutants) harbored mutations in gene mexZ, the product
      of which down-regulates expression of operon mexXY. Eight of the 12 strains
      exhibited mutations in genes known to control transcription of operon mexAB-oprM,
      such as mexR (four nalB mutants) or PA3721 (three nalC mutants). One strain was a
      nalB/nalC double mutant. For MexAB-OprM as well as for MexXY, no clear
      correlation could be established between (i) the types of mutations, (ii) the
      over-expression levels of genes mexA or mexX, and (iii) the resistance levels to
      effluxed antibiotics. Finally, three and four isolates overproduced MexXY (agrW
      mutants) or MexAB-OprM (nalD mutants), respectively, without any mutation in the
      known regulator genes. These data show that clinical isolates are able to broaden
      their drug resistance profiles by coexpressing two Mex efflux pumps and suggest
      the existence of additional regulators for MexAB-OprM and MexXY.

PMID- 15465265
TI  - [Comparison of two reverse hybridization methods for mycobacterial identification
      in clinical practice].
AB  - AIM OF THE STUDY: To evaluate the performance of two commercial methods for
      identification of Mycobacterium species: InnoLiPA Mycobacteria first version
      (Innogenetics) versus Genotype MTBC and Genotype Mycobacterium (HAIN) on,
      respectively, 2123 and 2164 distinct isolates. MATERIALS AND METHODS: Both
      techniques are based on the reverse hybridization of PCR products to their
      complementary probes immobilized on membrane strips. The InnoLiPA assay targets
      the 16S-23S rRNA spacer region. The HAIN test is composed of two kits: Genotype
      MTBC, for identification of tuberculosis complex mycobacteria, is based on gyrB
      DNA sequence polymorphism. Genotype Mycobacterium kit targets the 23S rDNA for
      identification of mycobacteria other than tuberculosis (MOTT) and tuberculosis
      complex mycobacteria. Both assays identify complex tuberculosis mycobacteria and
      respectively, eight and 12 species of MOTT. Moreover, the Genotype MTBC allows
      species differentiation within the M. tuberculosis complex. RESULTS: Eighty-eight
      percent and 95% of mycobacteria were identified by InnoLiPA and HAIN,
      respectively. Hybridization remained negative for 11% of isolates with InnoLiPA
      and 4% with HAIN. An identification of MOTT was obtained by conventional
      identification in all cases after the use of InnoLiPA. MOTT and one M.
      tuberculosis was obtained after HAIN procedure. Unidentified species were
      complementary to a specific probe in 5% of the cases with InnoLiPA and 17% with
      HAIN. CONCLUSION: HAIN identifies more mycobacteria species than does InnoLiPA
      and allows identification in the M. tuberculosis complex. However, failure in
      identification occurs only with MOTT with InnoLiPA when one M. tuberculosis was
      found among mycobacteria non identified with HAIN.

PMID- 15465266
TI  - [Advantages and limits of the surveillance of nosocomial infections from the
      microbiology laboratory: experience of Meaux hospital].
AB  - To estimate the incidence of nosocomial infections (NI) in our hospital and to
      increase healthcare professionals' awareness of hygiene, a prospective study was
      performed between January and December 2002 from the microbiology laboratory
      data. On 1334 suspicions of NI, corresponding to 1062 patients, sent to the
      hygiene correspondents in each medical care unit, the infection control team
      received 853 answers (64% of sendings) with 430 NI validated. The incidence rate
      of NI validated was 1.7 NI/1000 days of hospitalisation and 1.6 NI/100
      inpatients. The NI were predominantly related to urinary tract (47%), bloodstream
      (14%), and lower respiratory tract (12%). Transmission of these informations to
      medical information department permitted a valorisation of additional 16,000 ISA
      points. This prospective study permitted to develop a network of hygiene
      correspondents in every medical care units. None of the medical care units was
      unharmed by NI but the exhaustive declaration of NI seems difficult to realise.
      This study permitted to point out some dysfunctionments in the management of
      invasive procedures and to improve these practices.

PMID- 15465267
TI  - [Methicillin-resistant Staphylococcus aureus nosocomial infections in ICU: risk
      factors, morbidity and cost].
AB  - OBJECTIVE: Methicillin resistance and infections caused by methicillin-resistant
      Staphylococcus aureus represent a growing problem and a challenge for health-care
      institutions. We evaluated risk factors, morbidity and cost of infections caused
      by methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) Staphylococcus
      aureus. DESIGN: We performed an un-matched case-control study in an 20-bed
      medical intensive care unit from 1994-2001 at Nantes teaching hospital, France.
      All patients with pneumonia, bacteraemia and urinary MRSA (cases) or MSSA
      (controls) nosocomial infections were included in the study. RESULTS: Twenty four
      patients with MRSA infection were compared to 64 patients with MSSA infections.
      Patients with MRSA infection were older (56 vs. 45 years, P < 0.01), had longer
      length of stay (47 vs. 35 days, P < 0.05) and were infected later (22 vs. 10
      days, P < 0.00001) than patients with MSSA infection. No difference was observed
      between the two groups according to the Omega index, acute simplify index and
      mortality. MRSA infections involved extra cost due to antimicrobial treatment
      (184 vs. 72 Euros, P < 0.005) and length of stay (37,278 vs. 27,755 Euros, P <
      0.05). CONCLUSION: Patient infected by MRSA seems to be different from patient
      infected by MSSA but without consequence on Omega index and mortality. But
      methicillin-resistance involves extra cost due to antimicrobial treatment and
      length of stay.

PMID- 15465268
TI  - [Increased susceptibility to non-beta-lactam antimicrobial agents of MRSA
      isolates: relationship between genotype and antibiotype].
AB  - The objective of our study was to investigate the relationship between molecular
      epidemiology and antibiotic susceptibility of MRSA during a four-year period. In
      this aim, we determined the antibiotype of all MRSA identified during a yearly
      period of 3 months and typed 50 consecutive non-replicate MRSA isolates of each
      year. We also recorded antibiotic use. Susceptibility rates to gentamicin,
      tobramycin and ofloxacin remained stable, respectively, 95, 16 and 4%. In
      contrast, the proportion of MRSA susceptible to erythromycin progressively
      increased from 7.0% to 32.5% (P < 0.001). PFGE analysis of genomic DNA from the
      200 isolates revealed 15 different clones. We identified two epidemic clones,
      which contained 150 (clone A) and 28 isolates (clone C), respectively. The
      proportion of isolates belonging to clone A decreased during the study from 86%
      to 66%. Conversely, clone C increased from 4% to 22%. The increase of
      erythromycin-susceptibility within MRSA was caused by the emergence of clone C.
      Non-epidemic strains were more frequently susceptible to ofloxacin (31.8% vs.
      1.1%) and tobramycin (45.4% vs. 16.8%) than epidemic strains. Antimicrobial use
      had not significantly varied during the study. The proportion of beta-lactams,
      fluoroquinolones, macrolides and aminosides was 71.8, 13.9, 5.0 and 3.8% of the
      total antibiotic use, respectively. In our hospital, MRSA isolates became more
      susceptible to antimicrobial of minor use. The selection pressure exerted by beta
      lactams and fluoroquinolones was in favor of the spread of strains resistant to
      these both major antibiotic classes.

PMID- 15465269
TI  - [Screening for Staphylococcus aureus with a reduced susceptibility to vancomycin
      in: a Belgian hospital].
AB  - The aim of the present study was to investigate the prevalence of vancomycin
      resistance in clinical methicillin resistant Staphylococcus aureus (MRSA)
      isolates in our hospital by screening on Mueller-Hinton agar with 5 mg/l
      teicoplanin (MH-Teico), as recommended by the Comite de l'Antibiogramme of the
      Societe Francaise de Microbiologie (CA-SFM). Seventeen of 1002 clinical MRSA
      isolated from 404 patients showed in 2003 growth of at least four colonies on
      this medium, but only one was confirmed as homogeneous vancomycin-resistant S.
      aureus (VISA) and five as heterogeneous VISA (hVISA) by population analysis. None
      of the patients presented with severe infection but awareness is needed and
      screening on MH-Teico as recommended by CA-SFM is a convenient method.
      Surveillance should be focused on patients with risk factors for selection of
      such strains: patients with a prolonged course of glycopeptide therapy and
      persistence of MRSA infection or colonization.

PMID- 15465270
TI  - [Emergence of macrolide resistant Streptococcus pyogenes strains in pediatric
      patients in France].
AB  - A total of 206 recent throat isolates of Streptococcus pyogenes collected between
      2002 and 2004 from children were tested for their susceptibility to penicillin,
      amoxycillin, erythromycin, clarythromycin and clindamycin. The erythromycin
      resistant isolates were further studied for their genetic mechanism of resistance
      by means of PCR. In all, 14.5% of the strains were erythromycin resistant and
      13.5 and 1% expressed the constitutive MLS(B) and M resistance phenotypes and
      harbored the ermB and mef A genes respectively.

PMID- 15465271
TI  - [Resistance to linezolid in Staphylococcus aureus before its release].
AB  - Resistance to antibiotics is a global problem in geriatric centres. OBJECTIVE:
      The aim of this study was to determine the frequency of the resistance to
      linezolid in Staphylococcus aureus strains before its release in a geriatric
      centre. METHOD: From 03-01-01 to 03-04-30 linezolid was included in the panel of
      antibiotics tested in S. aureus strains. The susceptibilities were estimated by
      the disk diffusion test in routine clinical microbiology practice. RESULTS: A
      total of 213 strains of S. aureus was analysed. All of them were susceptible to
      the following antibiotics: linezolid, cotrimoxazol, fosfomycin, and
      glycopeptides. The meticillin-resistant S. aureus (MRSA) represented 67.1% (60.3
      73.3) strains. The resistance to pefloxacin, tobramycin and erythromycin
      concerned 92.3% (86.3-95.9), 73.4% (65.3-80.3) and 31.5% (24.1-39.8) of MRSA
      strains respectively. The MRSA strains were less resistant to the following
      antimicrobial drugs: gentamicin 7.0% (3.6-12.8), fusidic acid 2.1% (0.5-6.5) and
      rifampicin 1.4% (0.2-5.5). The resistance concerning at the same time gentamicin,
      pefloxacin and fucidic acid represented 2.1% (0.5-6.5) of SARM strains,
      rifampicin was not interested. CONCLUSION: Linezolid was effective in vitro in S.
      aureus strains regardless their susceptibilities in meticillin. According to its
      effectiveness in vivo, linezolid may be of use for the treatment of infections
      due to MRSA. However, there has been two reports of resistance of MRSA in
      clinical infections. The use of linezolid has to follow the instructions and it
      should be carefully monitored.

PMID- 15465272
TI  - [E.coli from urinary tract infections and acute pyelonephritis of children: 1% of
      strains are resistant to a subset of third generation cephalosporins].
AB  - E. coli remains the most often isolated pathogen in community urinary tract
      infections in children. We reported a retrospective study of antibiotic
      susceptibility of 506 E. coli strains isolated from urine. We found that 53% of
      the strains were resistant to amoxicilline and 22% to cotrimoxazole. The
      frequency of resistance to amoxicillin-clavulanic acid was of 7%, 40% of the
      strains were just intermediary and 53% were sensitive. Only five strains (1%)
      were resistant to ceftazidime: two mechanisms of resistance, hyperproduction of
      TEM betalactamase (3 cases) and cephalosporinase (2 cases), were suggested. This
      study illustrates the necessity of constant monitoring of bacterial resistance to
      adapt antibiotherapeutic guidelines to local evolution.

PMID- 15465273
TI  - Molecular mechanisms of neurodegeneration and neuroprotection--experimental
      approaches and the diseased brain.

PMID- 15465274
TI  - Tau-inclusion body formation in oligodendroglia: the role of stress proteins and
      proteasome inhibition.
AB  - Filamentous tau-positive inclusions in neurons and glia are a unifying mechanism
      underlying a variety of late onset neurodegenerative disorders termed
      "tauopathies". Oligodendroglial lesions and white matter pathology have long been
      underestimated and are specifically prominent in frontotemporal dementias (FTDs),
      such as Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal
      degeneration (CBD) and frontotemporal dementia with Parkinsonism linked to
      chromosome 17 (FTDP-17). Oligodendrocytes contain an extensive microtubule
      network and express the microtubule-associated protein tau. Tau-positive
      inclusion bodies in oligodendrocytes are positively stained with antibodies
      against ubiquitin and heat shock proteins (HSPs). Specifically the small HSP
      alphaB-crystallin has been identified in oligodendroglial lesions. HSPs act as
      molecular chaperones and prevent the accumulation of abnormal proteins, and
      support proteolytic degradation by targeting non-reparable proteins to the
      ubiquitin proteasomal pathway. HSPs and the proteasomal system closely work
      together. The present report summarizes recent data on HSP induction and
      aggregate formation in oligodendroglia cell culture systems, indicating that
      posttranslational modification of tau, HSP induction and alterations of the
      proteasomal system, which might occur during aging and disease processes, are
      involved in the neuropathological events leading to aggregate formation and
      degeneration.

PMID- 15465275
TI  - Amyloid-induced neurofibrillary tangle formation in Alzheimer's disease: insight
      from transgenic mouse and tissue-culture models.
AB  - Of all forms of dementia, Alzheimer's disease is the most prevalent. It is
      histopathologically characterized by beta-amyloid-containing plaques, tau
      containing neurofibrillary tangles, reduced synaptic density and neuronal loss in
      selected brain areas. For the rare familial forms of Alzheimer's disease,
      pathogenic mutations have been identified in both the gene encoding the precursor
      of the Abeta peptide, APP, itself and in the presenilin genes which encode part
      of the APP-protease complex. For the more frequent sporadic forms of Alzheimer's
      disease, the pathogenic trigger has not been unambiguously identified. Whether
      Abeta is again the main cause remains to be heavily discussed. In a related
      disorder termed frontotemporal dementia, which is characterized by tangles in the
      absence of beta-amyloid deposition, mutations have been identified in tau which
      also lead to neurodegeneration and dementia. For Alzheimer's disease the
      existence of familial forms lead to the proposition of the amyloid cascade
      hypothesis, which claims that beta-amyloid causes or enhances the tangle
      pathology. In this review, we describe tau transgenic mouse models in which
      aspects of the tau-associated pathology, including tangle formation, has been
      achieved. Moreover, tau transgenic mouse and tissue-culture models were used to
      test the amyloid cascade hypothesis. In addition, we discuss alternative
      hypotheses to explain the sporadic forms. The animal and tissue-culture models
      will provide insight into the underlying biochemical mechanisms of tau
      aggregation and nerve cell degeneration. These mechanisms may be partially shared
      between sporadic Alzheimer's disease, the familial forms and frontotemporal
      dementia. Eventually, Alzheimer's disease may be redefined based on biochemical
      events rather than phenotype.

PMID- 15465276
TI  - New players in old amyloid precursor protein-processing pathways.
AB  - The amyloid precursor protein (APP) gives rise to beta-amyloid peptides, which
      are the main constituents of senile plaques in brains of Alzheimer's disease (AD)
      patients. The generation of beta-amyloid peptides requires the enzymatic activity
      of the beta-site APP-cleaving enzyme 1 (BACE1). BACE1 is primarily expressed by
      neurons and increased BACE1 protein concentrations and enzymatic activities have
      been reported in the brains of AD patients. However, there is accumulating
      evidence that, in addition to neurons, reactive astrocytes are capable of
      expressing BACE1 and, therefore, may contribute to beta-amyloid plaque formation.
      This suggests that conditions accompanied by chronic astrocyte activation may
      contribute to developing AD. Non-amyloidogenic processing of the APP can be
      stimulated by phorbol esters (PEs) and by intracellular diacylglycerol (DAG)
      generation. This led to the hypothesis that classical and novel protein kinase Cs
      (PKCs), which are activated by DAG/PEs, regulate APP processing. However, in
      addition to PKCs, there are other DAG/PE receptors present in neurons which may
      participate in the modulation of APP processing. Munc13-1, a presynaptic protein
      with an essential role in synaptic vesicle priming, represents such an
      alternative target of the DAG second messenger pathway. Using Munc13-1 knock-out
      mice and human neuroblastoma cells transfected with wild-type and mutant Munc13-1
      constructs it was demonstrated that Munc13-1 acts independently of and in
      parallel with PKC to modulate APP metabolism. Therefore, agonists specific for
      the Munc13-1 C1-domain or small molecules mimicking the function of the
      endogenous Munc13-1 activator RIM1 may prove useful to shift APP processing
      towards the non-amyloidogenic pathway.

PMID- 15465277
TI  - Aging-related increase in oxidative stress correlates with developmental pattern
      of beta-secretase activity and beta-amyloid plaque formation in transgenic Tg2576
      mice with Alzheimer-like pathology.
AB  - The molecular mechanisms of beta-amyloidogenesis in sporadic Alzheimer's disease
      are still poorly understood. To reveal whether aging-associated increases in
      brain oxidative stress and inflammation may trigger onset or progression of beta
      amyloid deposition, a transgenic mouse (Tg2576) that express the Swedish double
      mutation of human amyloid precursor protein (APP) was used as animal model to
      study the developmental pattern of markers of oxidative stress and APP
      processing. In Tg2576 mouse brain, cortical levels of soluble beta-amyloid (1-40)
      and (1-42) steadily increased with age, but significant deposition of fibrillary
      beta-amyloid in cortical areas did not occur before postnatal age of 10 months.
      The slope of increase in cerebral cortical beta-secretase (BACE1) activities in
      Tg2576 mice between ages of 9 and 13 months was significantly higher as compared
      to that of the alpha-secretase, while the expression level of BACE1 protein and
      mRNA did not change with age. The activities of superoxide dismutase and
      glutathione peroxidase in cortical tissue from Tg2576 mice steadily increased
      from postnatal age 9-12 months. The levels of cortical nitric oxide, and reactive
      nitrogen species demonstrated peak values around 9 months of age, while the level
      of interleukin-1beta steadily increased from postnatal month 13 onwards. The
      developmental temporal coincidence of increased levels of reactive nitrogen
      species and antioxidative enzymes with the onset of beta-amyloid plaque
      deposition provides further evidence that developmentally and aging-induced
      alterations in brain oxidative status exhibit a major factor in triggering
      enhanced production and deposition of beta-amyloid, and potentially predispose to
      Alzheimer's disease.

PMID- 15465278
TI  - Neuronal trauma model: in search of Thanatos.
AB  - Trauma to the nervous system triggers responses that include oxidative stress due
      to the generation of reactive oxygen species (ROS). DNA is a major macromolecular
      target of ROS, and ROS-induced DNA strand breaks activate poly(ADP
      ribose)polymerase-1 (PARP-1). Upon activation PARP-1 uses NAD(+) as a substrate
      to catalyze the transfer of ADP-ribose subunits to a host of nuclear proteins. In
      the face of extensive DNA strand breaks, PARP-1 activation can lead to depletion
      of intracellular NAD(P)(H) pools, large decreases in ATP, that threaten cell
      survival. Accordingly, inhibition of PARP-1 activity after acute oxidative injury
      has been shown to increase cell survival. When NGF-differentiated PC12 cells, an
      in vitro neuronal model, are exposed to H(2)O(2) there is increased synthesis of
      poly ADP-ribose and decreases in intracellular NAD(P)(H) and ATP. Addition of the
      chemical PARP inhibitor 3-aminobenzamide (AB) prior to H(2)O(2) exposure blocks
      the synthesis of poly ADP-ribose and maintains intracellular NAD(P)(H) and ATP
      levels. H(2)O(2) injury is characterized by an immediate, necrotic cell death 2h
      after injury and a delayed apoptotic-like death 12-24h after injury. This
      apoptotic-like death is characterized by apoptotic membrane changes and apoptotic
      DNA fragmentation but is not associated with measurable caspase-3 activity. AB
      delays cell death beyond 24h and increases cell survival by approximately 25%.
      This protective effect is accompanied by significantly decreased necrosis and the
      apoptotic-like death associated with H(2)O(2) exposure. AB also restores caspase
      3 which can be attributed to the activation of the upstream activator of caspase
      3, caspase-9. Thus, the maintenance of intracellular ATP levels associated with
      PARP-1 inhibition shifts cell death from necrosis to apoptosis and from apoptosis
      to cell survival. Furthermore, the shift from necrosis to apoptosis may be
      explained, in part, by an energy-dependent activation of caspase-9.

PMID- 15465279
TI  - Role of cytokines and chemokines in prion infections of the central nervous
      system.
AB  - Prion infections of the central nervous system (CNS) are characterised by a
      reactive gliosis and the subsequent degeneration of neuronal tissue. The
      activation of glial cells, which precedes neuronal death, is likely to be
      initially caused by the deposition of misfolded, proteinase K-resistant, isoforms
      (termed PrP(res)) of the prion protein (PrP) in the brain. Cytokines and
      chemokines released by PrP(res)-activated glia cells may contribute directly or
      indirectly to the disease development by enhancement and generalisation of the
      gliosis and via cytotoxicity for neurons. However, the actual role of prion
      induced glia activation and subsequent cytokine/chemokine secretion in disease
      development is still far from clear. In the present work, we review our present
      knowledge concerning the functional biology of cytokines and chemokines in prion
      infections of the CNS.

PMID- 15465280
TI  - Neurodegeneration and plasticity.
AB  - Neurofibrillary degeneration, associated with the formation of paired helical
      filaments (PHF), is one of the critical neuropathological hallmarks of
      Alzheimer's disease (AD). Although the microtubule-associated protein tau in a
      hyperphosphorylated form has been established as primary PHF constituent, the
      process of tau phosphorylation and its potential link to degeneration is not very
      well understood, mostly because of the lack of a physiological in vivo model of
      PHF-like tau phosphorylation. PHF formation in AD follows a hierarchical pattern
      of development throughout different cortical areas, which closely matches the
      pattern of neuronal plasticity in the adult brain. Those brain areas are most
      early and most severely affected which are involved in the regulation of memory,
      learning, perception, self-awareness, consciousness, and higher brain functions
      that require a life-long re-fitting of connectivity, a process based on a
      particularly high degree of plasticity. Failures of synaptic plasticity are,
      thus, assumed to represent early events in the course of AD that eventually lead
      to alteration of tau phosphorylation. Recently, we have used the hibernation
      cycle, a physiological model of adaptation associated with an extraordinary high
      degree of structural neuronal plasticity, to analyze the potential link between
      synaptic plasticity, synaptic detachment and the regulation of tau
      phosphorylation. During torpor, a natural state of hypothermia, synaptic contacts
      between mossy fibers and hippocampal pyramidal neurons undergo dramatic
      regressive changes that are fully reversible very rapidly during euthermy. This
      rapid, reversible, and repeated regression of synaptic and dendritic components
      on CA3 neurons is associated with a reversible PHF-like phosphorylation of tau at
      a similar time course. The repeated formation and degradation of PHF-tau might,
      thus, represent a physiological mechanism not necessarily associated with
      pathological effects. These findings implicate an essential link between neuronal
      plasticity and PHF-like phosphorylation of tau, potentially involved in
      neurofibrillary degeneration.

PMID- 15465281
TI  - High throughput approaches in neuroscience.
AB  - Traditional approaches to understanding biological problems are now being
      advanced with the use of high throughput technologies, which analyse multiple
      samples simultaneously, or thousands of analytes in a single sample. The
      application of these technologies in neurochemistry and neuroscience is beginning
      to be explored and is assisting in the development of new models of drug action,
      neuroanatomical investigations, and in identifying molecular pathways involved in
      neurological and psychiatric disease. Tools such as microarray-based gene
      expression profiling and 2D and multidimensional proteomic methods are uncovering
      functional components to a wide variety of neuroscience paradigms and the
      application of these technologies is set to become standard in analysis.

PMID- 15465282
TI  - Blood-cell-specific acetylcholinesterase splice variations under changing
      stimuli.
AB  - Developmental and trauma-induced mechanism(s) that modify inflammation and immune
      responses in blood cells were recently found to be regulated by acetylcholine.
      Here, we report corresponding blood cell-specific changes in acetylcholinesterase
      splice variants. Plasmon resonance and flow cytometry using acetylcholinesterase
      variant-specific antibody probes, revealed a progressive increase in myeloid cell
      fractions expressing the apoptosis-related acetylcholinesterase-S variant from
      newborns to adult controls and post-delivery mothers. Hematopoietic cell
      fractions positive for the myeloproliferative acetylcholinesterase-R variant,
      were similarly high in post-partum blood, both intracellular and on the cell
      surface. Moreover, intracellular acetylcholinesterase-S protein amounts as
      reflected by fluorescence intensity measurements remained unchanged in myeloid
      cells from post-partum mothers as compared with matched controls. Unlike brain
      neurons, which over-express intracellular acetylcholinesterase-R under stress,
      lymphocytes from post-partum mothers presented increased surface
      acetylcholinesterase-S and pronounced decreases in both the expression and
      contents of surface acetylcholinesterase-R. Peripheral stimuli-induced
      modulations in acetylcholine regulation may hence reflect blood cell lineage
      dependent acetylcholinesterase splice variations.

PMID- 15465283
TI  - Turning the heterogeneous into homogeneous: studies on selectively isolated
      GABAergic interneuron subsets.
AB  - The amazing morphological and electrophysiological diversity of cortical
      GABAergic interneurons subserves the broad diversity of processes these cells
      modulate in neuronal networks. Until recently, interneuron development and
      functions have been extensively studied in heterogeneous in vitro and in vivo
      systems containing both excitatory and inhibitory components. However, mechanisms
      of interneuron specification during development, key signaling mechanisms
      controlling the establishment of particular inhibitory neuron subsets, and the
      spatial and temporal regulation of their integration in neuronal microcircuits
      remain poorly understood. Selective isolation of particular interneuron subsets
      may significantly extend our knowledge on the scenario of neurochemical and
      electrophysiological specification of developing interneurons, identification of
      signaling cues directing their axon growth, and principles of their anterograde
      and retrograde synaptic communication with other cell types. Here, we show that
      selective isolation of perisomatic inhibitory cells containing either parvalbumin
      or cholecystokinin reveals major differences in the temporal dynamics of their
      functional differentiation, and their dependence on target-derived signals like
      brain-derived neurotrophic factor and endocannabinoids. In addition, we discuss
      therapeutic prospects of modulating increased excitatory output in the
      hippocampus and subthalamic nucleus by re-adjusting the inhibitory control of
      principal cells.

PMID- 15465284
TI  - Selective changes in expression of different nicotinic receptor subtypes in brain
      and adrenal glands of mice carrying human mutated gene for APP or over-expressing
      human acetylcholinestrase.
AB  - In this study, we investigated regulatory mechanisms and plasticity of the
      nicotinic acetylcholine receptors (nAChRs) in the brain and adrenal glands of two
      transgenic mice models over-expressing human beta-amyloid precursor protein
      (APP(SWE)Tg) and human AChE enzyme (hAChE-Tg), respectively. All animals were
      studied at 3 months of age. Binding studies showed higher (125)I-alpha
      bungarotoxin (alpha7 nAChRs) and (3)H-epibatidine (alpha3 and alpha4 nAChRs)
      binding in the brain cortex and adrenal glands of hAChE-Tg mice compared to
      control mice. The APP(SWE)Tg mice showed a significantly lower relative level for
      the alpha4 mRNA in the brain cortex as well as a lower level of alpha3 mRNA, and
      higher level of alpha7 mRNA in the adrenal glands compared to control mice. A
      higher relative mRNA level of alpha3 and alpha4 nAChRs was observed in the brain
      as well as of alpha3 and alpha7 nAChRs in the adrenal glands of hAChE-Tg mice
      compared to control mice. Different nicotinic receptor plasticity is revealed in
      the brain cortex and adrenal glands in two transgenic mice models with different
      underlying pathophysiological mechanisms. Deposition of beta-amyloid (Abeta) may
      impair neurotransmitter activity in brain as well as in the adrenal gland.

PMID- 15465285
TI  - Role of Ca2+-independent phospholipase A2 and n-3 polyunsaturated fatty acid
      docosahexaenoic acid in prostanoid production in brain: perspectives for
      protection in neuroinflammation.
AB  - Various diseases of the central nervous system are characterized by induction of
      inflammatory events, which involve formation of prostaglandins. Production of
      prostaglandins is regulated by activity of phospholipases A(2) and
      cyclooxygenases. These enzymes release the prostaglandin precursor, the n-6
      polyunsaturated fatty acid, arachidonic acid and oxidize it into prostaglandin
      H(2). Docosahexaenoic acid, which belongs to the n-3 class of polyunsaturated
      fatty acids, was shown to reduce production of prostaglandins after in vivo and
      in vitro administration. Nevertheless, the fact that in brain tissue cellular
      phospholipids naturally have a uniquely high content of docosahexaenoic acid was
      ignored so far in studies of prostaglandin formation in brain tissue. We consider
      the following possibilities: docosahexaenoic acid might attenuate production of
      prostaglandins by direct inhibition of cyclooxygenases. Such inhibition was found
      with the isolated enzyme. Another possibility, which has been already shown is
      reduction of expression of inducible cyclooxygenase-2. Additionally, we propose
      that docosahexaenoic acid could influence intracellular Ca(2+) signaling, which
      results in changes of activity of Ca(2+)-dependent phospholipase A(2), hence
      reducing the amount of arachidonic acid available for prostaglandin production.
      Astrocytes, the main type of glial cells in the brain control the release of
      arachidonic acid, docosahexaenoic acid and the formation of prostaglandins. Our
      recently obtained data revealed that the release of arachidonic and
      docosahexaenoic acids in astrocytes is controlled by different isoforms of
      phospholipase A(2), i.e. Ca(2+)-dependent phospholipase A(2) and Ca(2+)
      independent phospholipase A(2), respectively. Moreover, the release of
      arachidonic and docosahexaenoic acids is differently regulated through Ca(2+)-
      and cAMP-dependent signal transduction pathways. Based on analysis of the current
      literature and our own data we put forward the hypothesis that Ca(2+)-independent
      phospholipase A(2) and docosahexaenoic acid are promising targets for treatment
      of inflammatory related disorders in brain. We suggest that Ca(2+)-independent
      phospholipase A(2) and docosahexaenoic acid might be crucially involved in brain
      specific regulation of prostaglandins.

PMID- 15465286
TI  - c-Jun N-terminal kinases (JNKs) and the cytoskeleton--functions beyond
      neurodegeneration.
AB  - The c-Jun N-terminal kinases (JNKs) are important mediators of neurodegeneration
      and their actions include the activation of genetic programs by phosphorylation
      of the nuclear transcription factor c-Jun/AP-1, the release of cytochrome c or
      the pro-inflammatory actions of microglia. Recent data, however, provide evidence
      for physiological functions of JNKs in particular JNK1, and this involves a role
      of JNKs in the development of the brain and the (functional and/or structural)
      integrity of the cytoskeleton. Here we summarize our findings on the cytoskeleton
      associated actions of JNKs. Thus, JNKs the relevant MAP kinases for the NGF
      induced formation and elongation of PC12 cells, and this process is also
      supported by JNK2 and JNK3 which are commonly considered as pro-apoptotic signal
      transducers. Importantly, JNK3 is also mandatory for the intact differentiation
      of neurons since the functional deletion of JNK3 caused apoptotic features such
      as activation of caspase 3 in untreated P0 primary hippocampal neurons and
      following glutamate excitotoxicity. Finally, we can visualize the presence of
      JNKs at the cytoskeleton, axon and growth cones of primary hippocampal neurons
      and PC12 cells, and this pattern changes following excitatory stimulation with
      glutamate. Thus, the functional role of JNKs during development and
      differentiation substantially differs from their degenerative actions in the
      adult brain.

PMID- 15465287
TI  - Purinergic modulation of extracellular glutamate levels in the nucleus accumbens
      in vivo.
AB  - In the present study, the P2 receptor-mediated modulation of the extracellular
      glutamate concentration was investigated by microdialysis in the nucleus
      accumbens (NAc) of freely moving rats. Because of the known interference of
      dopaminergic and glutamatergic mechanisms in this area the experiments were
      performed with animals intra-accumbally treated with 6-hydroxydopamine (6-OHDA)
      to deplete dopamine pools. Perfusion of the NAc with the prototypic P2 receptor
      agonist 2-methylthioadenosine 5'-triphosphate (2-MeSATP, 0.1, 1 and 10mM)
      concentration-dependently increased the extracellular level of glutamate in this
      area. Pretreatment with the P2 receptor antagonist pyridoxalphosphate-6-azophenyl
      2',4'-disulphonic acid (PPADS, 0.1mM) decreased the basal extracellular glutamate
      concentration and inhibited the 2-MeSATP-induced outflow of glutamate. In rats
      treated with 6-OHDA, 2-MeSATP increased the total extracellular glutamate to an
      extent about fivefold larger than in sham-lesioned rats. The perfusion of the
      dopamine-depleted NAc with the D(2)/D(3) dopamine receptor agonist quinpirole
      (0.1mM) diminished the basal concentration of glutamate and reduced the effect of
      2-MeSATP on the extracellular glutamate. These results provide evidence that the
      stimulation of P2 receptors is involved in the increase of accumbal extracellular
      glutamate in vivo. This behaviourally relevant mechanism depends on a dopamine
      D(2) receptor-mediated tone in the nucleus accumbens. Furthermore, the inhibition
      of P2 receptors may prevent, at least partly, glutamate-mediated
      neurodegeneration.

PMID- 15465288
TI  - Bilateral volume reduction of the insular cortex in patients with schizophrenia:
      a volumetric MRI study.
AB  - The morphologic changes of the insular cortex have been described in
      schizophrenia, but with inconsistencies between reports. We investigated the
      insular cortex volume by magnetic resonance imaging in 59 schizophrenia patients
      (31 males, 28 females) and 62 age- and gender-matched healthy controls (31 males,
      31 females). The insular cortex volume was measured on consecutive coronal 1-mm
      slices. Volumes of the left and right insular cortex were significantly reduced
      in schizophrenia patients compared with control subjects. There were no effects
      of gender on the insular cortex volume in the patient group or control subjects.
      Bilateral insular cortex volumes were correlated negatively with illness duration
      in the patient group. The findings of this study suggest that there is a possible
      progressive loss of the gray matter volume of the bilateral insular cortices
      subsequent to the onset of schizophrenia.

PMID- 15465289
TI  - Localized volume reduction in prefrontal, temporolimbic, and paralimbic regions
      in schizophrenia: an MRI parcellation study.
AB  - Functional and structural abnormalities of the anterior cingulate gyrus (ACG) in
      patients with schizophrenia have been repeatedly reported. However, one remaining
      issue is whether gray matter volume reduction in ACG exists to an extent
      comparable with, or even in excess of, that in other prefrontal and temporolimbic
      regions. High-spatial-resolution magnetic resonance imaging was performed on
      patients with schizophrenia (n=27) and on age-, gender-, and parental
      socioeconomic-status-matched healthy control subjects (n=27). After the gray and
      white matter were semiautomatically segmented, whole prefrontal and temporal
      lobes were manually parceled into 15 subregions-by-two hemispheres (30 regions of
      interest) constituting seven prefrontal gray matter regions, six temporal gray
      matter regions, the prefrontal white matter, and the temporal white matter.
      Compared with healthy subjects, schizophrenic patients showed significant gray
      matter volume reduction in the bilateral ACG, this being the largest effect size
      (left, 0.84; right, 0.56) among all the regions examined. There were also
      significant gray matter volume reductions in the bilateral posterior STG,
      bilateral inferior frontal gyrus, left posterior amygdala-hippocampal complex
      (mostly hippocampus), and the left insula. These results suggest that gray matter
      volume reductions in the ACG are prominent among prefrontal and temporolimbic
      regions in patients with schizophrenia. These findings indicate the importance of
      ACG abnormalities in the pathophysiology of schizophrenia.

PMID- 15465290
TI  - Association between cognitive performance and striatal dopamine binding is higher
      in timing and motor tasks in patients with schizophrenia.
AB  - The basal ganglia have received increasing attention with regard to their role in
      time pacing, motor function and other components of cognition. The aim of this
      study was to test whether the finer the motor activity and/or time perception
      performance were, the higher the striatal dopamine D(2) binding would be. Single
      photon emission computed tomography (SPECT) with [(123)I]iodobenzamide (IBZM) was
      performed to measure striatal D(2) receptor densities. A battery of
      neuropsychological tests, including the Wisconsin Card Sorting Test (WCST), the
      finger tapping test (FTT), and an attention test, was performed by patients with
      schizophrenia. Results indicated a strong correlation between the FTT score and
      striatal D(2) receptor binding. Neuroleptic dosage plays an important role in the
      relationship between cognitive tasks and striatal dopamine receptor densities. In
      addition, the striatal D(2) receptor density is more significantly correlated
      with attentional tests that consider the time effect than those that do not.
      Among the three tests performed, the WCST was least significantly correlated with
      striatal D(2) receptor densities. A decrease in striatal dopamine D(2) receptor
      density seems to be associated with impaired performance on optimal timing tasks
      and motor processing in patients with schizophrenia.

PMID- 15465291
TI  - Cerebral phosphorus metabolite and transverse relaxation time abnormalities in
      heroin-dependent subjects at onset of methadone maintenance treatment.
AB  - Cerebral bioenergetic and phospholipid abnormalities have been reported in heroin
      dependent subjects. The goal of the present study was to characterize the
      neurochemical profile of subjects voluntarily enrolled in a methadone maintenance
      (MM) treatment program to overcome their heroin addiction. Participants included
      43 heroin-dependent subjects during their first month of MM and 15 age-matched
      healthy individuals. Phosphorus magnetic resonance spectroscopy ((31)P MRS) and
      transverse relaxation times (T2-RT), which can reflect steady state cerebral
      perfusion and metabolism, were acquired at 1.5 T from an axial slice prescribed
      through the orbitofrontal and occipital cortices, including basal ganglia and
      frontal cortex. MM subjects exhibited reduced phosphocreatine (PCr) levels (
      15.3%), elevated phosphodiesters (+ 12.9%, PDE) and significantly longer T2-RT
      ((+) 2.1%) compared with healthy comparison subjects. When MM subjects were
      stratified into subgroups based on treatment duration, we found a treatment
      duration effect on metabolite values but not T2-RT; reduced PCr was observed only
      after 8+ days of MM, and phosphomonoesters (PME) were elevated in the 15-28 day
      MM group. Taken together, these cross-sectional data suggest that the first month
      of MM treatment may be associated with altered cerebral bioenergetics and
      phospholipid metabolite levels.

PMID- 15465292
TI  - Reduced area of the corpus callosum in posttraumatic stress disorder.
AB  - Magnetic resonance imaging (MRI) studies have revealed decreases in the mid
      sagittal area of the corpus callosum (CC) in pediatric posttraumatic stress
      disorder (PTSD), but at present no data are available in adult PTSD patients. We
      have previously reported decreased whole-brain white matter (WM) volume in adults
      with PTSD and now report corpus callosum area from the same sample. MRI was used
      to obtain whole-brain images in 12 adult patients with PTSD and 10 matched
      controls. Total parenchyma (white matter plus gray matter [GM]) volume, mid
      sagittal area of the CC and seven sub-regions of this structure were calculated.
      In PTSD patients, the total CC area, absolute and normalized to total brain
      parenchyma, was smaller compared with control values. Several absolute and
      normalized CC sub-regions were also smaller in PTSD patients: genu (region 2),
      mid-body (region 5) and isthmus (region 6). There was also a trend for the
      anterior mid-body (area 4) to be smaller in PTSD patients. No differences were
      found in the rostrum (region 1), rostral body (region 3) or splenium (region 7).
      Adult patients with PTSD had decreased CC area after correcting for total brain
      tissue, indicating that these differences are not attributable to generalized
      white matter atrophy. These findings are similar to previous results in children
      with PTSD and suggest specific changes in the CC.

PMID- 15465293
TI  - EEG mapping in patients with social phobia.
AB  - Recent studies have suggested an information-processing bias in social phobia
      (SP). Little is known about the electrophysiological correlates of anxiety in SP.
      The aim of the present study was to investigate the quantitative
      electroencephalogram (EEG) in 25 drug-free patients with SP as compared with age-
      and sex-matched normal controls and to correlate anxiety and depressive symptoms
      with EEG data. EEG was recorded under vigilance-controlled and resting
      conditions. The Spielberger State and Trait Anxiety Scale (STAI) and the Beck
      Depression Inventory (BDI) were administered to assess anxiety and depression
      levels. Multivariate analysis of variance revealed significant differences
      between patients and controls, specifically frontopolarly and right centrally.
      Statistical analysis demonstrated a decrease in absolute and relative delta,
      theta power, alpha-adjacent slow-beta and fast beta power and an increase in
      absolute and relative intermediate beta power, as well as an acceleration of the
      total centroid and a slowing in beta centroid and its variability. Trait anxiety
      and depression scores correlated positively with the dominant alpha frequency and
      the alpha centroid, and negatively with absolute theta and slow alpha power as
      well as with the centroid of the delta/theta frequency band. In conclusion, EEG
      mapping in patients with SP revealed significant differences from normal controls
      suggesting a hyperarousal as a pathogenetic factor of anxiety.

PMID- 15465294
TI  - P300 event-related potentials and cognitive function in social phobia.
AB  - The aim of the study was to investigate abnormalities of event-related potentials
      (ERPs) in social phobia patients indicating deficits in speed and amount of
      perceptual and cognitive resources as well as relationships between ERPs and
      cognitive functioning. ERPs were recorded from 19 EEG leads in a two-tone oddball
      paradigm in medication-free patients with DSM-IV social phobia (n=25) and in age-
      and sex-matched healthy controls (HC). Neuropsychological test performance was
      administered. Compared with the HC group, patients with social phobia showed
      reductions in N1 at temporal leads, N2 and P300 amplitudes, predominantly
      centroparietally, and longer P300 latencies. The observed P300 latency
      prolongation was associated with reduced Non-Verbal Learning Test (NVLT) but not
      the Wisconsin Card Sorting Test (WCST) scores. The reduction in N1 amplitude
      indicates an impairment in perceptual processing. The reduced P300 amplitudes may
      reflect reduced cognitive resources for the evaluation of relevant information.
      The increased P300 latency, indicating longer stimulus evaluation time, was
      correlated to deficits in learning processes as measured by the Non-Verbal
      Learning Test but not to executive function as measured by the Wisconsin Card
      Sorting Test. It may therefore be concluded that social phobia patients show
      deficits in cognitive information processing as reflected by ERPs.

PMID- 15465295
TI  - Increased frontal cortical folding in autism: a preliminary MRI study.
AB  - The gyrification index (GI), the ratio of total to outer cortical contour, was
      applied to measure the cerebral folding patterns in autism. GI was examined on a
      frontal coronal slice obtained from MRI scans of 30 nonmentally retarded
      individuals with autism and 32 matched healthy controls. In the autistic group,
      left frontal GI was higher in children and adolescents but not in adults.
      Cortical folding was decreased bilaterally with age in the total autistic sample
      but not in controls. These preliminary findings suggest that the gyrification
      patterns in autism may be abnormal, which could be related to the various
      cortical anomalies observed in this disorder.

PMID- 15465296
TI  - MRI of the brainstem in patients with major depression, bipolar affective
      disorder and normal controls.
AB  - Structural imaging studies of bipolar affective disorder or major depression have
      shown a spectrum of abnormal findings. However, a characteristic pattern of
      abnormality for either disease has not yet emerged. While the majority of studies
      focused on brain atrophy and the volumes of supratentorial cerebral structures,
      little attention has been paid to infratentorial structures. This MRI study
      focused on the pontomesencephalic area including the region of the raphe nuclei.
      The raphe nuclei are of special interest in affective disorders as they are the
      origin of the major serotonergic projections in this region. MRI scans of 10
      bipolar I patients, 10 patients with major depression and 10 age-matched healthy
      control subjects were studied. The brain stem and the fourth ventricle areas as
      well as T2-relaxation times in the area of the raphe nuclei were evaluated. A
      difference between patients with major depression and control subjects for T(2)
      relaxation times was found in a region of interest located along the midline of
      the pons. No difference was found between patients with bipolar disorder and
      control subjects. This finding needs to be replicated in a larger sample with
      more elaborated MRI techniques (multi-echo sequences) for the determination of T2
      relaxation times.

PMID- 15465297
TI  - Flocculation and coalescence of droplets in oil-in-water emulsions formed with
      highly hydrolysed whey proteins as influenced by starch.
AB  - The effects of added unmodified amylopectin starch, modified amylopectin starch
      and amylose starch on the formation and properties of emulsions (4 wt.% corn oil)
      made with an extensively hydrolysed commercial whey protein (WPH) product under a
      range of conditions were examined. The rate of coalescence was calculated based
      on the changes in the droplet size of the emulsions during storage at 20 degrees
      C. The rates of creaming and coalescence in emulsions containing amylopectin
      starches were enhanced with increasing concentration of the starches during
      storage for up to 7 days. At a given starch concentration, the rate of
      coalescence was higher in the emulsions containing modified amylopectin starch
      than in those containing unmodified amylopectin starch, whereas it was lowest in
      the emulsions containing amylose starch. All emulsions containing unmodified and
      modified amylopectin starches showed flocculation of oil droplets by a depletion
      mechanism. However, flocculation was not observed in the emulsions containing
      amylose starch. The extent of flocculation was considered to correlate with the
      rate of coalescence of oil droplets. The different rates of coalescence could be
      explained on the basis of the strength of the depletion potential, which was
      dependent on the molecular weight and the radius of gyration of the starches. At
      high levels of starch addition (>1.5%), the rate of coalescence decreased
      gradually, apparently because of the high viscosity of the aqueous phase caused
      by the starch.

PMID- 15465298
TI  - Bilayer thickness in unilamellar extruded 1,2-dimyristoleoyl and 1,2-dierucoyl
      phosphatidylcholine vesicles: SANS contrast variation study of cholesterol
      effect.
AB  - Small-angle neutron scattering on extruded unilamellar vesicles in water was used
      to study bilayer thickness when cholesterol (CHOL) was added at 44.4 mol% to 1,2
      dimyristoleoylphosphatidylcholine (diC14:1PC) and 1,2
      dierucoylphosphatidylcholine (diC22:1PC) bilayers. Using the (1)H(2)O/(2)H(2)O
      contrast variation and the small-angle form of Kratky-Porod approximation, the
      bilayer gyration radii at infinite contrast R(g,infinity) and the bilayer
      thickness parameters d(g,infinity) = 12(0.5)R(g,infinity) were obtained at 30
      degrees C. Addition of cholesterol to diC14:1PC increased the d(g,infinity) from
      3.72 +/- 0.02 to 4.26 +/- 0.01 nm, while in the diC22:1PC bilayers the
      d(g,infinity) change observed was within the experimental error: +0.23 +/- 0.23
      nm.

PMID- 15465299
TI  - Precision control of the surface structure of gelatin films using micropit
      plates.
AB  - We attempted to use micropit plates as a silicon mold in order to control the
      surface structures of gelatin films. The three-dimensional micropit plates,
      fabricated with micromachining technology, have uniform quadrangular or circular
      pits with side lengths or diameters from 25-400 microm and depths of 40 microm.
      The micropit plates were originally hydrophilic because of silanol groups on the
      surface. In order to facilitate peeling the aqueous gelatin film from the
      micropit plates, the plate was therefore modified with hexamethyldisilazane.
      Gelatin films with precisely microfabricated structures on the surfaces were
      obtained by using the modified micropit plates. The release behavior of the films
      with different surface structures was examined.

PMID- 15465300
TI  - Enhanced stabilization of aerosol-OT surfactant monolayer upon interaction with
      small amounts of bovine serum albumin at the air-water interface.
AB  - An investigation is made of the influence from small amounts of the protein
      bovine serum albumin (BSA) on the lateral organization of low molecular weight
      surfactant sodium bis-2-ethylhexyl sulfosuccinate (AOT) at the air-water
      interface. Surface pressure (pi - A), surface potential (deltaV - A) and Brewster
      angle microscopy (BAM) experiments were carried out, with particular emphasis on
      the monolayer stability under successive compression-expansion cycles. AOT
      monolayer is not stable at the air-water interface, which means that the majority
      of AOT molecules go into the aqueous subphase as monomers and/or normal micelles.
      When a waiting time elapses between spreading and compression, the surfactant
      monolayer tends to reorganize partially at the air-water interface, with a
      monolayer expansion being observed for waiting times as large as 12 h. The
      incorporation of very small amount of BSA (10(-9)M) at the interface, also
      inferred from BAM, increases the monolayer stability as revealed by pi - A and
      deltaV - A results. For a waiting time of circa 3 h, the mixed monolayer reaches
      its maximum stability. This must be related to protein (and/or protein-surfactant
      complexes) adsorbed onto the AOT monolayer, thus altering the BSA conformation to
      accommodate its hydrophobic/hydrophilic residues. Furthermore, the effects from
      such small amounts of BSA in the monolayer formation and stabilization mean that
      the AOT monolayer responds cooperatively to BSA.

PMID- 15465301
TI  - Chromatic immunoassay based on polydiacetylene vesicles.
AB  - A new approach of chromatic immunoassay based on polydiacetylene vesicles is
      described. Antibodies were covalently coupled with mixed vesicles of 10,12
      tricosadiynoic acid (TCDA) and dimyristoylphosphatidycholine (DMPC). The vesicle
      antibody conjugates were irradiated with UV light to yield a blue-colored
      polydiacetylene. After antigen injection, specific immunoreactions took place at
      the vesicle surface alter polydiacetylene conformation and lead to a color change
      from blue to red. The chromatic immunoassay described here is simple, rapid,
      sensitive; the color change was readily discernible by naked eye when the
      concentration of antigen is 1 ng/mL. Incorporation of DMPC in the mixed vesicles
      increases the sensitivity of the chromatic immunoassay.

PMID- 15465302
TI  - Effect of acid-base interaction between silica and fragrant oil in the PCL/PEG
      microcapsules.
AB  - In this work, the biodegradable poly(epsilon-caprolactone) (PCL)/poly(ethylene
      glycol) (PEG) microcapsules were prepared in the presence of SiO(2) and fragrant
      oil using emulsion solvent evaporation method. And SiO(2) was chemically treated
      in 30 wt.% hydrochloric acid and sodium hydroxide. The effect of chemical
      treatment on SiO(2) surfaces was studied in terms of pH, acid-base value, and
      N(2)/77 K gas adsorption. Image analyzer and scanning electron microscope (SEM)
      were used to observe the shape and surface change of the prepared microcapsules.
      And the variation of surface free energy of microcapsules was characterized by
      contact angles. The results showed that the average diameter, surface free
      energy, and fragrant oil release rate of microcapsules were increased with
      increasing the PEG ratio. Also, it was found that in the case of basic treated
      SiO(2), the fragrant oil adsorption capacity and release rate were decreased due
      to the decrease of specific surface area or the increase of acid-base
      interactions between basic SiO(2) and acidic fragrant oil.

PMID- 15465303
TI  - Laser flash photolysis and time-resolved fluorescence measurements of the
      aggregation number of SDS-biopolymer complexes.
AB  - Aqueous solutions of 0.5% sodium carboxymethyl cellulose, NaCMC, and 2
      hydroxyethyl cellulose, HEC, and variable concentration of sodium dodecyl
      sulfate, SDS, were studied by the intensities ratio of pyrene fluorescence bands
      (I/III and monomer/excimer) and conductance measurements to determine the
      critical aggregation concentration, cac, and the degree of micellar dissociation,
      alpha, respectively. The cac of these systems is close to 2-4 x 10(-3)M and
      values of alpha are consistent with the formation of SDS micelles adsorbed
      cooperatively to the polymer backbone. Laser flash photolysis (LFP) and time
      resolved fluorescence (TRF) techniques were employed to determine the micellar
      aggregation number, N, using the probes flavone and pyrene, respectively. The
      obtained N for HEC/SDS and NaCMC/SDS were 48 and 68, respectively. The presence
      of the counterions at the NaCMC backbone is the main factor responsible for this
      number. Besides, the transient spectra of flavone and present in 0.5% HEC or
      NaCMC with and in absence of SDS are discussed. Flavone triplet state exit rate
      constant from the biopolymer/SDS complexes showed that these systems are
      completely different from a pure SDS micelle.

PMID- 15465304
TI  - Surface modification using photocrosslinkable chitosan for improving
      hemocompatibility.
AB  - Immobilization of the anticoagulative or antithrombogenic biomolecule has been
      considered as one of the important methods to improve the blood compatibility of
      artificial biomaterials. In this study, a novel immobilization reaction scheme
      was utilized to incorporate O-butyrylchitosan (OBCS) onto the activated glass
      surface with an aim to develop an anticoagulative substrate. Activation of the
      glass surface was carried out by silanization and then OBCS was grafted to the
      silanized surface via a radiation grafting technique. The OBCS-grafted glass
      surfaces were characterized by electron spectroscopy for chemical analysis (ESCA)
      and atomic force microscopy (AFM). The blood compatibility of the OBCS-grafted
      glass was evaluated by platelet rich plasma (PRP) contacting experiments and
      protein adsorption experiments in vitro. These results have demonstrated that the
      surface with immobilized OBCS shows much less platelet adhesive and fibrinogen
      adsorption compared to the control surface. Therefore, the novel reaction scheme
      proposed here is very promising for future development of an anticoagulative
      glass substrate.

PMID- 15465305
TI  - An electrodynamics-based model for ion diffusion in microbial polysaccharides.
AB  - An electrodynamics-based model was formulated for simulation of ion diffusion in
      microbial polysaccharides. The fixed charges and electrostatic double layers that
      may associate with microbial polysaccharides and their effects on ion diffusion
      were explicitly built into the model. The model extends a common multicomponent
      ion diffusion formulation that is based on irreversible thermodynamics under a
      zero ionic charge flux condition, which is only applicable to the regions without
      fixed charges and electrostatic double layers. An efficient numerical procedure
      was presented to solve the differential equations in the model. The model well
      described key features of experimental observations of ion diffusion in
      negatively charged microbial polysaccharides including accelerated diffusive
      transport of cations, exclusion of anions, and increased rate of cation transport
      with increasing negative charge density. The simulated diffusive fluxes of
      cations and anions were consistent with a cation exchange diffusion concept in
      negatively charged polysaccharides at the interface of plant roots and soils; and
      the developed model allows to mathematically study such diffusion phenomena. An
      illustrative example was also provided to simulate dynamic behavior of ionic
      current during ion diffusion within a charged bacterial cell wall polysaccharide
      and the effects of the ionic current on the compression or expansion of the
      bacterial electrostatic double layer at the interface of the cell wall and bulk
      solution.

PMID- 15465306
TI  - Calorimetric and structural investigation of the interaction of lysozyme and
      bovine serum albumin with poly(ethylene oxide) and its copolymers.
AB  - This work reports investigations aiming at verifying the occurrence of specific
      interactions between lysozyme or bovine serum albumin (BSA) and poly(ethylene
      oxide) and its copolymers with poly(propylene oxide). Thermal stability of these
      proteins, followed by means of high sensitivity DSC, was found to be mostly
      unaffected by the presence of these polymers. Chromatographic experiments
      (reverse-phase HPLC and size exclusion chromatrography) did not reveal any sign
      of specific interaction for these mixtures, either. Isothermal titration
      calorimetry revealed an increase in enthalpy for the mixtures, represented by a
      positive enthalpy of transfer for these proteins from buffer to polymer
      solutions. Moreover, SAXS analyses confirmed that at ambient temperatures these
      polymers do not affect lysozyme structure. In summary, no evidence is found to
      support earlier suggestions that some kind of complex could be formed between
      these proteins and poly(ethylene oxide) or its copolymers, but the present
      results suggest the occurrence of entropically driven hydrophobic effects.

PMID- 15465307
TI  - Effect of defect size on fracture strength of dental low fusion porcelain.
AB  - Various grinding defects were produced on the surface of specimen dental low
      fusion porcelain in an attempt to establish the relationship between defect size
      and fracture strength. In addition, the applicability of the process zone size
      fracture criterion in assessing the material properties of dental low fusion
      porcelain was examined. Super porcelain AAA E3 (Noritake Co., Japan) was used as
      dental low fusion porcelain. The bending strength and fracture toughness value
      were estimated by the three-point bending test. After glazing, grinding flaws
      were introduced by grinding the specimen with abrasive papers of various mesh
      sizes. In order to calculate the fracture toughness value of dental low fusion
      porcelain, we introduced a surface crack using a Vickers indenter. The results
      were discussed based on the process zone size-fracture criterion. The size of
      cracks caused by grinding was estimated with the process zone size-fracture
      criterion and Newman-Raju formula. As the defect size decreased, the fracture
      stress approached the strength for smooth specimen without defect. The K(c) value
      showed a tendency to approach the K(lc) value when the defect size increased. The
      relationship between the fracture stress, sigma(F), and the equivalent crack
      length, a(e), was in good agreement with the theoretical relations deduced from
      the criterion in dental low fusion porcelain.

PMID- 15465308
TI  - Application of transmission diffusing wave spectroscopy to the study of gelation
      of milk by acidification and rennet.
AB  - Transmission diffusing wave spectroscopy has been used to study and compare three
      milk gelling systems (acid gelation of heated and unheated milks and rennet
      coagulation of unheated milk). In all cases, DWS was able to demonstrate the
      point of gelation as indicated by a rapid increase in particle size, as well as
      the small decreases in casein micelle radius attributed to the collapse or
      removal of the hairy kappa-casein layer. More importantly, the photon transport
      mean free path (l(*)) was measured. This parameter is unique to transmission DWS
      and can potentially give information about developing microstructures and the
      mechanical properties between different types of gels. The values of l(*) changed
      during the gelation processes, and these changes were manifested earlier than any
      change in particle aggregation or rheology of the systems. All three different
      gelling systems showed different changes in l(*) with time, showing the
      development of different interactions as the acidification or renneting reactions
      proceeded. Although a full analysis of the l(*) parameter and its changes cannot
      be made, it is concluded that they can provide important information on the pre
      gelation states of aggregating systems.

PMID- 15465309
TI  - Preferential partitioning of uncharged local anesthetics into the surface
      adsorbed film.
AB  - The surface tension and pH of aqueous solutions of three hydrochloric acid (HCl) 
      uncharged anesthetic (mepivacaine (MC), bupibacaine (BC) and dibucaine (DC))
      mixtures were measured as a function of total molality and composition of local
      anesthetic in order to investigate the competitive surface-adsorption of
      uncharged and charged local anesthetics. The behavior of the surface tension
      versus total molality and pH versus total molality curves remarkably changed at
      the composition corresponding to an equimolar mixture. The pH measurements showed
      that uncharged and charged forms coexisted only at compositions more than the
      equimolar mixture. The partitioning quantities of respective uncharged and
      charged anesthetics into the surface-adsorbed film were estimated from their
      surface densities calculated thermodynamically. The greater quantity of uncharged
      anesthetics existed in the adsorbed film at the coexisting composition, that is,
      the uncharged anesthetics adsorbed more preferentially than charged ones. The
      relative ease with which uncharged anesthetics transferred into the surface
      adsorbed film was proportional to the hydrophobicities and well correlated the
      anesthetic potencies. At compositions in the vicinity of physiological pH (ca.
      7.4), the bulk solution is more abundant in charged anesthetics than uncharged
      ones, whereas the uncharged molecules is conversely more abundant in the surface
      region. The present results clearly imply that the surface-active molecule of
      local anesthetic in the physiological pH is the uncharged form and the
      partitioning is greatly dependent on the hydrophobicity among the anesthetics.

PMID- 15465311
TI  - Nanomechanics of adhesion proteins.
AB  - Recent advances in molecular force measurements have resulted in the
      quantification of the nanomechanical properties of single molecular bonds, and
      elucidated novel relationships between molecular architecture and biomolecular
      adhesion. The measured forces to rupture single intermolecular bonds revealed
      novel and unexpected ways that proteins respond to mechanical force. Measurement
      of the magnitude of interprotein forces and the distances over which they act
      further determined how protein architecture may contribute to both the stability
      and structural organization of adhesive junctions.

PMID- 15465312
TI  - Single-molecule spectroscopic methods.
AB  - Being praised for the mere fact of enabling the detection of individual
      fluorophores a dozen years ago, single-molecule techniques nowadays represent
      standard methods for the elucidation of the structural rearrangements of
      biologically relevant macromolecules. Single-molecule-sensitive techniques, such
      as fluorescence correlation spectroscopy, allow real-time access to a multitude
      of molecular parameters (e.g. diffusion coefficients, concentration and molecular
      interactions). As a result of various recent advances, this technique shows
      promise even for intracellular applications. Fluorescence imaging can reveal the
      spatial localization of fluorophores on nanometer length scales, whereas
      fluorescence resonance energy transfer supports a wide range of different
      applications, including real-time monitoring of conformational rearrangements (as
      in protein folding). Still in their infancy, single-molecule spectroscopic
      methods thus provide unprecedented insights into basic molecular mechanisms.

PMID- 15465313
TI  - Linear dichroism of biomolecules: which way is up?
AB  - Understanding the organization of molecules in naturally occurring ordered arrays
      (e.g. membranes, protein fibres and DNA strands) is of great importance to
      understanding biological function. Unfortunately, few biophysical techniques
      provide detailed structural information on these non-crystalline systems. UV,
      visible and IR linear dichroism have the potential to provide such information.
      Recent advances in technology and simulations allow this potential to be
      fulfilled, and can now provide a detailed understanding of the molecular
      mechanisms of such fundamental biological processes as amyloid fibre formation
      and membrane protein folding.

PMID- 15465314
TI  - Automation of NMR structure determination of proteins.
AB  - The automation of protein structure determination using NMR is coming of age. The
      tedious processes of resonance assignment, followed by assignment of NOE (nuclear
      Overhauser enhancement) interactions (now intertwined with structure
      calculation), assembly of input files for structure calculation, intermediate
      analyses of incorrect assignments and bad input data, and finally structure
      validation are all being automated with sophisticated software tools. The
      robustness of the different approaches continues to deal with problems of
      completeness and uniqueness; nevertheless, the future is very bright for
      automation of NMR structure generation to approach the levels found in X-ray
      crystallography. Currently, near completely automated structure determination is
      possible for small proteins, and the prospect for medium-sized and large proteins
      is good.

PMID- 15465315
TI  - Structural and dynamic studies of proteins by solid-state NMR spectroscopy: rapid
      movement forward.
AB  - Starting only a few years ago, many solid-state NMR spectroscopy laboratories
      have become engaged in solving the complete structures of biological
      macromolecules using high-resolution methods based on magic angle spinning. These
      efforts typically involve structurally homogeneous samples, and utilize recently
      developed pulse sequences for the sequential correlation of resonances, the
      detection of tertiary contacts and the characterization of torsion angles.
      Thereby, systems have been studied that evaded other, more established, structure
      determination methods.

PMID- 15465316
TI  - The extended interface: measuring non-local effects in biomolecular interactions.
AB  - Improvements in the sensitivity and availability of biophysical techniques for
      the detection of the formation of complexes in solution are revealing that the
      effects of binding are not restricted to the direct contacts between the
      biomolecules or even to a localised site. Rather, information about the binding
      event is transmitted throughout the biomolecules and the surrounding solution
      through changes in the hydrogen bonding, hydration and electrostatic field as the
      complex is formed. Calorimetric, volumetric and NMR methods are beginning to
      provide a quantitative view of the nature and thermodynamic consequences of this
      extended interface, and the resulting data pose a major challenge for
      computational models of binding.

PMID- 15465317
TI  - Combining prediction, computation and experiment for the characterization of
      protein disorder.
AB  - Several computational and experimental methods exist for identifying disordered
      residues within proteins. Computational algorithms can now identify these
      disordered sequences and predict their occurrence within genomes with relatively
      high accuracy. Recent advances in NMR and mass spectroscopy permit faster and
      more detailed studies of disordered states at atomic resolutions. Combining
      prediction, computation and experimentation is proposed to accelerate and enhance
      the characterization of intrinsically disordered protein.

PMID- 15465319
TI  - Structure determination of macromolecular assemblies by single-particle analysis
      of cryo-electron micrographs.
AB  - A new generation of electron microscopes equipped with field emission gun
      electron sources and the ability to image molecules in their native environment
      at liquid nitrogen or helium temperatures has enabled the analysis of
      macromolecular structures at medium resolution (approximately 10 angstroms) and
      in different conformational states. The amalgamation of electron microscopy and X
      ray crystallographic approaches makes it possible to solve structures in the 100
      1000 angstroms size range, advancing our understanding of the function of complex
      assemblies. Many new structures have been solved during the past two years,
      including one of the smallest complexes to be determined by single-particle cryo
      electron microscopy, the transferrin receptor-transferrin complex. Other notable
      results include the near atomic level resolution structure of the nicotinic
      acetylcholine receptor in helical arrays and an icosahedral virus structure with
      an asymmetric polymerase resolved.

PMID- 15465318
TI  - Turning protein crystallisation from an art into a science.
AB  - Protein crystallisation has gained a new strategic and commercial relevance in
      the post-genomic era because of its pivotal role in structural genomics.
      Producing high-quality crystals has always been a bottleneck to structure
      determination and, with the advent of proteomics, this problem is becoming
      increasingly acute. The task of producing suitable crystals may be tackled using
      two approaches. The first relies on empirical techniques that are based mainly on
      trial and error, and what is perceived to be the 'art' of crystallisation. The
      second approach is aimed at gaining an understanding of the fundamental
      principles that govern crystallisation; this knowledge may be applied to design
      experimental methodology for producing high-quality crystals of medical and
      industrial interest.

PMID- 15465320
TI  - Carbohydrates and glycoconjugates: progress in non-mammalian glycosylation,
      glycosyltransferases, invertebrate lectins and carbohydrate-carbohydrate
      interactions.

PMID- 15465321
TI  - Structure and catalytic cycle of beta-1,4-galactosyltransferase.
AB  - Beta-1,4-galactosyltransferase-1, a housekeeping enzyme that functions in the
      synthesis of glycoconjugates, has two flexible loops, one short and one long.
      Upon binding a metal ion and UDP-galactose, the loops change from an open to a
      closed conformation, repositioning residues to lock the ligands in place.
      Residues at the N-terminal region of the long loop form the metal-binding site
      and those at the C-terminal region form a helix, which becomes part of the
      binding site for the oligosaccharide acceptor; the remaining residues cover the
      bound sugar-nucleotide. After binding of the oligosaccharide acceptor and
      transfer of the galactose moiety, the product disaccharide unit is ejected and
      the enzyme returns to the open conformation, repeating the catalytic cycle.

PMID- 15465322
TI  - Biosynthesis of human-type N-glycans in heterologous systems.
AB  - Insects, yeasts and plants generate widely different N-glycans, the structures of
      which differ significantly from those produced by mammals. The processing of the
      initial Glc2Man9GlcNAc2 oligosaccharide to Man8GlcNAc2 in the endoplasmic
      reticulum shows significant similarities among these species and with mammals,
      whereas very different processing events occur in the Golgi compartments. For
      example, yeasts can add 50 or even more Man residues to Man(8-9)GlcNAc2, whereas
      insect cells typically remove most or all Man residues to generate
      paucimannosidic Man(3-1)GlcNAc2N-glycans. Plant cells also remove Man residues to
      yield Man(4-5)GlcNAc2, with occasional complex GlcNAc or Gal modifications, but
      often add potentially allergenic beta(1,2)-linked Xyl and, together with insect
      cells, core alpha(1,3)-linked Fuc residues. However, genomic efforts, such as
      expression of exogenous glycosyltransferases, have revealed more complex
      processing capabilities in these hosts that are not usually observed in native
      cell lines. In addition, metabolic engineering efforts undertaken to modify
      insect, yeast and plant N-glycan processing pathways have yielded sialylated
      complex-type N-glycans in insect cells, and galactosylated N-glycans in yeasts
      and plants, indicating that cell lines can be engineered to produce mammalian
      like glycoproteins of potential therapeutic value.

PMID- 15465323
TI  - Protein glycosylation lessons from Caenorhabditis elegans.
AB  - From observations on human diseases and mutant mice, it has become clear that
      glycosylation plays a major role in metazoan development. Caenorhabditis elegans
      provides powerful tools to study this problem that are not available in men or
      mice. The worm has many genes homologous to mammalian genes involved in
      glycosylation. Glycobiologists have, in recent years, cloned and expressed some
      of these genes and studied the effects of mutations on worm development. Recent
      studies have focused on N-glycosylation, lumenal nucleoside diphosphatases, the
      resistance of C. elegans to a bacterial toxin and infections, fucosylation and
      proteoglycans.

PMID- 15465324
TI  - Structural and functional diversity of lectin repertoires in invertebrates,
      protochordates and ectothermic vertebrates.
AB  - During the past few years, substantial progress has been accomplished in the
      elucidation of the structural diversity of the lectin repertoires of
      invertebrates, protochordates and ectothermic vertebrates, providing particularly
      valuable information on those groups that constitute the invertebrate/vertebrate
      'boundary'. Although representatives of lectin families typical of mammals, such
      as C-type lectins, galectins and pentraxins, have been described in these taxa,
      the detailed study of selected model species has yielded either novel variants of
      the structures described for the mammalian lectin representatives or novel lectin
      families with unique sequence motifs, multidomain arrangements and a new
      structural fold. Along with the high structural diversity of the lectin
      repertoires in these taxa, a wide spectrum of biological roles is starting to
      emerge, underscoring the value of invertebrate and lower vertebrate models for
      gaining insight into structural, functional and evolutionary aspects of lectins.

PMID- 15465325
TI  - Carbohydrate-carbohydrate interactions in cell recognition.
AB  - Obtaining a better understanding of the molecular basis of cell recognition
      remains an important challenge with regard to the social functioning of cells in
      multicellular systems. The wide structural diversity of carbohydrates allows many
      combinatorial possibilities for fine-tuning cell-cell and cell-matrix recognition
      in multicellular organisms. Direct carbohydrate-carbohydrate interaction would
      endow both the flexibility and the specificity of reversible contacts at the cell
      surface during the formation, maintenance and pathogenesis of tissues. The recent
      development of methods for the characterization of such interactions will help to
      expand our knowledge of the mechanisms that trigger early events in cell
      recognition.

PMID- 15465326
TI  - Sulfone and phosphinic acid analogs of decaprenolphosphoarabinose as potential
      anti-tuberculosis agents.
AB  - Mycobacteria biosynthesize a cell wall structure that is rich in polysaccharides
      containing arabinofuranose residues. The source of these arabinofuranose residues
      is decaprenolphosphoarabinose (1), the donor substrate for mycobacterial
      arabinosyltransferases. We have previously demonstrated that an analog of 1, C
      phosphonate 7, prevented the growth of mycobacteria and this compound is
      currently undergoing testing for efficacy in tuberculosis-infected mice. We
      describe here the synthesis and testing of additional analogs of 1 that contain
      either a sulfone (8-14) or phosphinic acid (15-19) moiety in place of the
      phosphodiester functionality. Screening of these compounds in vitro against
      Mycobacterium tuberculosis strain H(37)Rv revealed that while some of these
      compounds possessed low to modest activity, none was as potent as 7.

PMID- 15465327
TI  - Synthesis and evaluation of fluorine-substituted 1H-pyrrolo[2,3-b]pyridine
      derivatives for dopamine D4 receptor imaging.
AB  - Seven fluorine-substituted 1H-pyrrolo[2,3-b]pyridine derivatives were synthesized
      based on a lead ligand, 3-[[4-(4-iodophenyl)piperazin-1-yl]-methyl]-1H
      pyrrolo[2,3-b]pyridine (L-750,667) and evaluated as potential dopamine D(4)
      receptor imaging agents by positron emission tomography (PET). Binding affinities
      of these ligands for the dopamine D(2), D(3), and D(4) receptor subtypes were
      measured in vitro. Most ligands showed high and selective binding for the D(4)
      receptor. Ligand 7 had high affinity for the D(4) receptor, whereas ligands 1, 2,
      and 6 showed high selectivity for the D(4) receptor. LogP values were calculated
      for the ligands in this series and ligand 6 had the lowest lipophilicity. (18)F
      labeled ligand 7 demonstrated a uniform regional brain distribution and a rapid
      washout in mice, probably due to nonspecific binding. Based on their in vitro
      binding properties and calculated logP values, ligand 6 appears to have the most
      promise for dopamine D(4) receptor imaging.

PMID- 15465328
TI  - Synthesis and antibacterial activity of novel and potent DNA gyrase inhibitors
      with azole ring.
AB  - The 4-piperidyl moiety and the pyrazole ring in 1-(3-chlorophenyl)-5-(4
      phenoxyphenyl)-3-(4-piperidyl)pyrazole 2, which has previously shown improved DNA
      gyrase inhibition and target-related antibacterial activity, were transformed to
      other groups and the in vitro antibacterial activity of the synthesized compounds
      was evaluated. The selected pyrazole, oxazole and imidazole derivatives showed
      moderate inhibition against DNA gyrase and topoisomerase IV with similar IC(50)
      values (IC(50)=9.4-25 microg/mL). In addition, many of the pyrazole, oxazole and
      imidazole derivatives synthesized in this study exhibited potent antibacterial
      activity against quinolone-resistant clinical isolates and coumarin-resistant
      laboratory isolates of Gram-positive bacteria with minimal inhibitory
      concentration values equivalent to those against susceptible strains.

PMID- 15465330
TI  - Electrophilicity index as a possible descriptor of biological activity.
AB  - The purpose of this study is to probe the suitability of DFT based chemical
      reactivity parameter, electrophilicity index as a possible biological activity
      descriptor in the development of QSAR. Testosterone derivatives with activity
      described in terms of various biological activity parameters and the estrogen
      derivatives by relative binding affinity (RBA) values have been selected as model
      systems. The implications for the ability of electrophilicity to describe the
      biological activities are discussed. From the results it is possible to observe
      that electrophilicity index may be suitable to effectively describe the
      biological activity.

PMID- 15465329
TI  - Effects of new ubiquinone-imidazo[2,1-b]thiazoles on mitochondrial complex I
      (NADH-ubiquinone reductase) and on mitochondrial permeability transition pore.
AB  - In this work we describe the synthesis of a series of imidazo[2,1-b]thiazoles and
      2,3-dihydroimidazo[2,1-b]thiazoles connected by means of a methylene bridge to
      CoQ(0). These compounds were tested as specific inhibitors of the NADH:ubiquinone
      reductase activity in mitochondrial membranes. The imidazothiazole system when
      bound to the quinone ring in place of the isoprenoid lateral side chain, may
      increase the inhibitory effect (with an IC(50) for NADH-Q(1) activity ranging
      between 0.25 and 0.96 microM) whereas the benzoquinone moiety seems to lose the
      capability to accept electrons from complex I as indicated by very low maximal
      velocity elicited by the compounds tested. Moreover the low rotenone sensitivity
      for almost all of these compounds suggests that they are only partially able to
      interact with the physiological ubiquinone-reduction site. The compounds were
      investigated for the capability of increasing the permeability transition of the
      inner mitochondrial membrane in isolated mitochondria. Unlike CoQ(0), which is
      considered a mitochondrial membrane permeability transition inhibitor, the new
      compounds were inducers.

PMID- 15465331
TI  - Brasilicardins B-D, new tricyclic terpenoids [correction of terpernoids] from
      actinomycete Nocardia brasiliensis.
AB  - Three new tricyclic terpenoids, brasilicardins B-D (2-4), were isolated together
      with brasilicardin A (1), a potent immunosuppressive compound, from the cultured
      broth of a pathogenic actinomycete Nocardia brasiliensis IFM0406, and the
      structures and stereochemistry were determined by spectroscopic data and a single
      crystal X-ray diffraction analysis. The immunosuppressive and cytotoxic
      activities of 2-4 were examined in the comparison with 1.

PMID- 15465332
TI  - Synthesis of new 6-alkylvinyl/arylalkylvinyl substituted 1,2,4-trioxanes active
      against multidrug-resistant malaria in mice.
AB  - 3-Alkyl/arylalkyl substituted 2-butenols 9, 10, 23a-d undergo regiospecific
      photooxygenation to furnish beta-hydroxyhydroperoxides 11, 12, 24a-d,
      respectively, in reasonable yields. Acid catalyzed condensation of 11, 12, 24a-d
      with various ketones furnish new 1,2,4-trioxanes 13-18, 25a-d, 26a-d, 27a-d in
      good yields. Several of these trioxanes show promising antimalarial activity
      against multidrug-resistant Plasmodium yoelii in mice by oral and intramuscular
      routes.

PMID- 15465333
TI  - Synthesis and antitumor activity of bicyclo[3.3.1]nonenol derivatives.
AB  - Various novel bicyclo[3.3.1.]nonenol derivatives were synthesized in an efficient
      one-pot procedure in a remarkably stereoselective reaction. The title compounds
      show significant antitumor activity against human cancer cell lines. A variety of
      cinnamic acid derivatives were linked to the title compounds as side chains in
      order to enhance the antitumor activity. These compounds were subjected to the in
      vitro antitumor screening, and the results are discussed. It seems important with
      respect to antitumor activity to locate an aromatic ring at the C-7 position of
      the bicyclo[3.3.1]nonane framework.

PMID- 15465334
TI  - Resveratrol analogues as selective cyclooxygenase-2 inhibitors: synthesis and
      structure-activity relationship.
AB  - Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is found in grapes and various
      medical plants. Among cytotoxic, antifungal, antibacterial cardioprotective
      activity resveratrol also demonstrates non-selective cyclooxygenase-1 (COX-1) and
      cyclooxygenase-2 (COX-2) inhibition. In order to find more selective COX-2
      inhibitors a series of methoxylated and hydroxylated resveratrol derivatives were
      synthesized and evaluated for their ability to inhibit both enzymes using in
      vitro inhibition assays for COX-1 and COX-2 by measuring PGE(2) production.
      Hydroxylated but not methoxylated resveratrol derivatives showed a high rate of
      inhibition. The most potent resveratrol compounds were 3,3',4',5-tetra-trans
      hydroxystilbene (COX-1: IC(50)=4.713, COX-2: IC(50)=0.0113 microM, selectivity
      index=417.08) and 3,3',4,4',5,5'-hexa-hydroxy-trans-stilbene (COX-1:
      IC(50)=0.748, COX-2: IC(50)=0.00104 microM, selectivity index=719.23). Their
      selectivity index was in part higher than celecoxib, a selective COX-2 inhibitor
      already established on the market (COX-1: IC(50)=19.026, COX-2: IC(50)=0.03482
      microM, selectivity index=546.41). Effect of structural parameters on COX-2
      inhibition was evaluated by quantitative structure-activity relationship (QSAR)
      analysis and a high correlation was found with the topological surface area TPSA
      (r=0.93). Docking studies on both COX-1 and COX-2 protein structures also
      revealed that hydroxylated but not methoxylated resveratrol analogues are able to
      bind to the previously identified binding sites of the enzymes. Hydroxylated
      resveratrol analogues therefore represent a novel class of highly selective COX-2
      inhibitors and promising candidates for in vivo studies.

PMID- 15465335
TI  - Design, synthesis, and biological activity of non-amidine factor Xa inhibitors
      containing pyridine N-oxide and 2-carbamoylthiazole units.
AB  - Based on the both of results for X-ray studies of tetrahydrothiazolopyridine
      derivative 1c and FXV673, we synthesized a series of thiazol-5-ylpyridine
      derivatives containing pyridine N-oxide and 2-carbamoylthiazole units to optimize
      the S4 binding element. N-Oxidation of thiazol-5-ylpyridine increased the anti
      fXa activity more than 10-fold independent on the position of N-oxide. The 4
      pyridine N-oxide derivatives 3a and 3d excelled over the
      tetrahydrothiazolopyridine 1b in potency. 2-Methylpyridine N-oxide 3d exhibited
      49-fold selectivity over thrombin. Our modeling study proposed a binding mode
      that the pyridine N-oxide ring of 3a stuck into the "cation hole" , and the oxide
      anion of 3a occupied in the almost same space to that of FXV673. From
      observations of the SAR and modeling studies, we suggested the possibilities that
      the formation of hydrogen bond with the oxide anion in the "cation hole" and the
      affinity of cationic pyridine ring to S4 subsite were responsible for increase in
      anti-fXa activity.

PMID- 15465336
TI  - A potential prodrug for a green tea polyphenol proteasome inhibitor: evaluation
      of the peracetate ester of (-)-epigallocatechin gallate [(-)-EGCG].
AB  - Green tea has been shown to have many biological effects, including effects on
      metabolism, angiogenesis, oxidation, and cell proliferation. Unfortunately, the
      most abundant green tea polyphenol (-)-epigallocatechin gallate or (-)-EGCG is
      very unstable in neutral or alkaline medium. This instability leads to a low
      bioavailability. In an attempt to enhance the stability of (-)-EGCG, we
      introduced peracetate protection groups on the reactive hydroxyls of (-)-EGCG
      (noted in text as 1). HPLC analysis shows that the protected (-)-EGCG analog is
      six times more stable than natural (-)-EGCG under slightly alkaline conditions. A
      series of bioassays show that 1 has no inhibitory activity against a purified 20S
      proteasome in vitro, but exhibits increased proteasome-inhibitory activity in
      intact leukemic cells over natural (-)-EGCG, indicating an intercellular
      conversion. Inhibition of cellular proteasome activity by 1 is associated with
      induction of cell death. Therefore, our results indicate that the protected
      analog 1 may function as a prodrug of the green tea polyphenol proteasome
      inhibitor (-)-EGCG.

PMID- 15465337
TI  - Studies on the immuno-modulating and anti-tumor activities of Ganoderma lucidum
      (Reishi) polysaccharides.
AB  - We describe here the isolation of Reishi polysaccharides for the study of their
      effect on cytokine expression in mouse splenocytes. A fraction (F3) has been
      shown to activate the expression of IL-1, IL-6, IL-12, IFN-gamma, TNF-alpha, GM
      CSF, G-CSF, and M-CSF, and from this three subfractions have been prepared where
      F3G1 activates IL-1, IL-12, TNF-alpha, and G-CSF, F3G2 activates all the
      cytokines as F3 does, and F3G3 activates only IL-1 and TNF-alpha. Together with
      previous studies, the mode of action on macrophages has been proposed where F3
      binds to TLR4 receptor and activates extracellular signal-regulated kinase (ERK),
      c-Jun N-terminal kinase (JNK) and p38 to induce IL-1 expression.

PMID- 15465338
TI  - Polysaccharides of Ganoderma lucidum alter cell immunophenotypic expression and
      enhance CD56+ NK-cell cytotoxicity in cord blood.
AB  - In our previous study, a fucose-containing glycoprotein fraction (F3), isolated
      from the water-soluble extracts of Ganoderma lucidum, was shown to stimulate mice
      spleen cell proliferation and cytokine expression. We now further investigate the
      effect of F3 on the immunophenotypic expression in mononuclear cells (MNCs). When
      human umbilical cord blood (hUCB) MNCs were treated with F3 (10-100 microg/mL)
      for 7days, the population of CD14+CD26+ monocyte/macrophage, CD83+CD1a+ dendritic
      cells, and CD16+CD56+ NK-cells were 2.9, 2.3, and 1.5 times higher than those of
      the untreated controls (p<0.05). B-cell population has no significant change. T
      cell growth was, however, slightly inhibited and CD3 marker expression decreased
      approximately 20% in the presence of higher concentrations of F3 (100 microg/mL).
      We also found that F3 is not harmful to human cells in vitro, and after F3
      treatment, NK-cell-mediated cytotoxicity was significantly enhanced by 31.7%
      (p<0.01) at effector/target cell ratio (E/T) 20:1, but was not altered at E/T
      5:1.

PMID- 15465339
TI  - Antioxidant properties of 3-hydroxycoumarin derivatives.
AB  - A series of hydroxylated 3-hydroxycoumarins was synthesised by the reaction of 3
      aryl-2-hydroxypropenoic derivatives with boron tribromide. They were evaluated
      for their ability to scavenge the 2,2-diphenyl-1-picrylhydrazyl radical, the
      superoxide anion radical, the hydroxyl radical and the peroxynitrite anion and to
      inhibit copper-induced human LDL peroxidation. The physicochemical results were
      in accordance to establish the compounds hydroxylated on C-6 and C-7 positions as
      the most active of the series with antioxidant potencies comparable to those of
      quercetin and vitamin C. These compounds form o- and p-quinonoid derivatives upon
      radical scavenging and may serve as new lead compounds for pharmacological
      investigations.

PMID- 15465340
TI  - Nucleotide analogues containing 2-oxa-bicyclo[2.2.1]heptane and l-alpha
      threofuranosyl ring systems: interactions with P2Y receptors.
AB  - The ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of the
      P2Y(1) receptor has been successfully substituted with a rigid methanocarba ring
      system, leading to the conclusion that the North (N) ring conformation is
      preferred in receptor binding. Similarly, at P2Y(2) and P2Y(4) receptors,
      nucleotides constrained in the (N) conformation interact equipotently with the
      corresponding ribosides. We now have synthesized and examined as P2Y receptor
      ligands nucleotide analogues substituted with two novel ring systems: (1) a (N)
      locked-carbocyclic (cLNA) derivative containing the oxabicyclo[2.2.1]heptane ring
      system and (2) l-alpha-threofuranosyl derivatives. We have also compared
      potencies and preferred conformations of these nucleotides with the known
      anhydrohexitol-containing P2Y(1) receptor antagonist MRS2283. A cLNA bisphosphate
      derivative MRS2584 21 displayed a K(i) value of 22.5 nM in binding to the human
      P2Y(1) receptor, and antagonized the stimulation of PLC by the potent P2Y(1)
      receptor agonist 2-methylthio-ADP (30 nM) with an IC(50) of 650 nM. The parent
      cLNA nucleoside bound only weakly to an adenosine receptor (A(3)). Thus, this
      ring system afforded some P2Y receptor selectivity. A l-alpha-threofuranosyl
      bisphosphate derivative 9 displayed an IC(50) of 15.3 microM for inhibition of 2
      methylthio-ADP-stimulated PLC activity. l-alpha-Threofuranosyl-UTP 13 was a P2Y
      receptor agonist with a preference for P2Y(2) (EC(50)=9.9 microM) versus P2Y(4)
      receptors. The P2Y(1) receptor binding modes, including rotational angles, were
      estimated using molecular modeling and receptor docking.

PMID- 15465341
TI  - Using a kinase screen to investigate the constituents of the sponge Stelletta
      clavosa obtained from diverse habitats.
AB  - Fourteen collections of the marine sponge Stelletta clavosa have been obtained
      from diverse Indo-Pacific locations in order to conduct a comparison of their
      major constituents. The dichloromethane extract of one collection (no. 00369)
      exhibited activity in a c-Raf-1 kinase assay. Bioactivity-directed isolation
      resulted in the known porphyrin analogs pyropheophorbide a (2) and purpurin 18
      methyl ester (3). Further spectroscopic screening of the various sponge extracts
      resulted in the isolation of four swinholide polyketides, a carotenoid, and three
      diketopiperazines. Pyropheophorbide a (2) exhibited the best IC(50) among the
      porphyrin type compounds (IC(50)<0.31microg/mL). This prompted further screening
      of 2 against a panel of 85 kinases.

PMID- 15465342
TI  - Synthesis and biological evaluation of bicyclic and tricyclic substituted
      nortropane derivatives: discovery of a novel selective alpha1D-adrenergic
      receptor ligand.
AB  - A range of 3,6,6-trisubstituted nortropane derivatives based upon 6beta
      phenyltropane-3beta,6 alpha-diol have been synthesised from 6beta
      hydroxytropinone, including some novel related tricyclic hemi-ketal and tricyclic
      ketal compounds. Derivatives were assessed for pharmacological affinity and
      selectivity at alpha(1)-adrenergic receptors, and 6beta-phenyl-8
      azabicyclo[3.2.1]octan-3-spiro-2'-(1',3'-dioxolane)-6-ol, a novel lead compound
      selective for the alpha(1D)-adrenergic receptor, is reported.

PMID- 15465343
TI  - Synthesis and anti-tubercular activity of a series of 2
      sulfonamido/trifluoromethyl-6-substituted imidazo[2,1-b]-1,3,4-thiadiazole
      derivatives.
AB  - A series of 2-sulfonamido/trifluoromethyl-6-(4'-substituted
      aryl/heteroaryl)imidazo[2,1-b]-1,3,4-thiadiazole derivatives (II) have been
      synthesized by reaction of 2-amino-5-sulfonamido/trifluoromethyl-1,3,4
      thiadiazoles and an appropriate alpha-haloaryl/heteroaryl ketones. Further 5
      bromo (III), 5-thiocyanato (IV), 5-gaunylhydrazone (V) derivatives were
      synthesized in order to study the effect of these substituents on biological
      activity. Structures of these compounds were established by IR, (1)H NMR, (13)C
      NMR, Mass and HRMS. The selected compounds were evaluated for their preliminary
      in vitro anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv
      strain using radiometric BACTEC and broth dilution assay methods. The results
      show that compounds 5, 7, 8, 10 and 12 exhibited moderate to good anti-tubercular
      activity with percentage inhibition of 29, 43, 58, 31 and 41, respectively, at a
      MIC of >6.25 microg/mL. Compound 18 showed a MIC of 20 microg/mL.

PMID- 15465344
TI  - Design and synthesis of highly potent and selective (2-arylcarbamoyl-phenoxy)
      acetic acid inhibitors of aldose reductase for treatment of chronic diabetic
      complications.
AB  - Recent efforts to identify treatments for chronic diabetic complications have
      resulted in the discovery of a novel series of highly potent and selective (2
      arylcarbamoyl-phenoxy)-acetic acid aldose reductase inhibitors. The compound
      class features a core template that utilizes an intramolecular hydrogen bond to
      position the key structural elements of the pharmacophore in a conformation,
      which promotes a high binding affinity. The lead candidate, example 40, 5-fluoro
      2-(4-bromo-2-fluoro-benzylthiocarbamoyl)-phenoxyacetic acid, inhibits aldose
      reductase with an IC(50) of 30 nM, while being 1100 times less active against
      aldehyde reductase, a related enzyme involved in the detoxification of reactive
      aldehydes. In addition, example 40 lowers nerve sorbitol levels with an ED(50) of
      31 mg/kg/d po in the 4-day STZ-induced diabetic rat model.

PMID- 15465345
TI  - Oxidised derivatives of silybin and their antiradical and antioxidant activity.
AB  - Carboxylic acids derived from silybin (1) and 2,3-dehydrosilybin (2) with
      improved water solubility were prepared by selective oxidation of parent
      compounds and a new inexpensive method for preparation of 2,3-dehydrosilybin from
      silybin was developed and optimised. The antioxidative properties of the above
      mentioned compounds and of side product 3a from oxidation of compound 1 were
      determined by cyclic voltammetry, free radical scavenging (DPPH, superoxide)
      assays, and by inhibition of in vitro generated liver microsomal lipid
      peroxidation. Dehydrogenation at C((2))-C((3)) in flavonolignans (silybin vs 2,3
      dehydrosilybin; silybinic acid vs 2,3-dehydrosilybinic acid) strongly improved
      antioxidative properties (analogously as in flavonoids taxifolin vs quercetin).
      Thus, in antioxidative properties, dehydrosilybin was superior to silybin by one
      order, but its water solubility is too low for application in aqueous milieu. On
      the other hand, 2,3-dehydrosilybinic acid is a fairly soluble derivative with
      antilipoperoxidation and antiradical activities better than that of silybin.

PMID- 15465346
TI  - Bicyclic peptidomimetic tetrahydrofuro[3,2-b]pyrrol-3-one and hexahydrofuro[3,2
      b]pyridine-3-one based scaffolds: synthesis and cysteinyl proteinase inhibition.
AB  - A stereoselective synthesis of (3aS,6aR)-tetrahydrofuro[3,2-b]pyrrol-3-ones and
      (3aS,7aR)-hexahydrofuro[3,2-b]pyridine-3-ones has been developed through Fmoc
      protected scaffolds 12 and 13. A key design element within these novel bicyclic
      scaffolds, in particular the 5,5-fused system, was the inherent stability of the
      cis-fused geometry in comparison to that of the corresponding trans-fused. Since
      the bridgehead stereocentre situated beta to the ketone was of a fixed and stable
      configuration, the fact that cis ring fusion is both kinetically and
      thermodynamically stable with respect to trans ring fusion provides chiral
      stability to the bridgehead stereocentre that is situated alpha to the ketone. To
      exemplify this principle, building blocks 12 and 13 were designed, prepared and
      utilised in a solid phase combinatorial synthesis of peptidomimetic inhibitors
      10, 45a-e, 11 and 46. Both series were chirally stable with 5,5-series 10 and 45a
      e exhibiting potent in vitro activity against a range of CAC1 cysteinyl
      proteinases. Compound 10, a potent and selective inhibitor of cathepsin K,
      possessed good primary DMPK properties along with promising activity in an in
      vitro cell-based human osteoclast assay of bone resorption.

PMID- 15465347
TI  - Synthesis and anticonvulsant evaluation of some new 2-substituted-3
      arylpyrido[2,3-d]pyrimidinones.
AB  - A series of 2-substituted-3-arylpyrido[2,3-d]pyrimidinones was prepared for
      evaluation as potential anticonvulsants. In murine screening, compounds 4a-c
      having a 2-oxo-2-(4-pyridyl)ethyl group in the 2-position and a 2-substituted
      phenyl moiety at the 3-position of the pyridopyrimidinone system displayed the
      most potent anti-seizure activity in both the maximal electroshock (MES) and
      pentylenetetrazol (scPTZ) tests at doses in the 3-10mg/kg range. Compound 4c
      showed no agonist activity at the GABA(A) receptor and was unable to block
      presynaptic sodium and calcium channels in vitro.

PMID- 15465348
TI  - Conformationally-restricted vigabatrin analogs as irreversible and reversible
      inhibitors of gamma-aminobutyric acid aminotransferase.
AB  - Compounds that inhibit gamma-aminobutyric acid aminotransferase exhibit
      anticonvulsant activity; vigabatrin is a known irreversible inhibitor of this
      enzyme and anticonvulsant drug. Conformationally-restricted, five-membered- and
      six-membered-ring vigabatrin analogs were synthesized and tested as inhibitors of
      gamma-aminobutyric acid aminotransferase. Two monofluorinated compounds, 4 and 5,
      are time-dependent inhibitors of the enzyme, and their potencies are comparable
      to that of vigabatrin. Compounds 6 and 7 are weak reversible inhibitors.

PMID- 15465349
TI  - Focus in honor of Carol V. Robinson, 2003 Biemann Medal awardee.

PMID- 15465350
TI  - Comparison of the binding stoichiometries of positively charged DNA-binding drugs
      using positive and negative ion electrospray ionization mass spectrometry.
AB  - Positive and negative ion electrospray ionization (ESI) mass spectra of complexes
      of positively charged small molecules (distamycin, Hoechst 33258,
      [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2) have been compared. [Ru(phen)2dpq]Cl2
      and [Ru(phen)2dpqC]Cl2 bind to DNA by intercalation. Negative ion ESI mass
      spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA showed
      ions from DNA-ligand complexes consistent with solution studies. In contrast,
      only ions from free DNA were present in positive ion ESI mass spectra of mixtures
      of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA, highlighting the need for
      obtaining ESI mass spectra of non-covalent complexes under a range of
      experimental conditions. Negative ion spectra of mixtures of the minor groove
      binder Hoechst 33258 with DNA containing a known minor groove binding sequence
      were dominated by ions from a 1:1 complex. In contrast, in positive ion spectra
      there were also ions present from a 2:1 (Hoechst 33258: DNA) complex, suggesting
      an alternative binding mode was possible either in solution or in the gas phase.
      When Hoechst 33258 was mixed with a DNA sequence lacking a high affinity minor
      groove binding site, the negative ion ESI mass spectra showed that 1:1 and 2:1
      complexes were formed, consistent with existence of binding modes other than
      minor groove binding. The data presented suggest that comparison of positive and
      negative ion ESI-MS spectra might provide an insight into various binding modes
      in both solution and the gas phase.

PMID- 15465351
TI  - Probing noncovalent protein-ligand interactions of the cGMP-dependent protein
      kinase using electrospray ionization time of flight mass spectrometry.
AB  - Nanoflow electrospray ionization time of flight mass spectrometry (ESI-TOF-MS)
      was used to study activation properties of the cGMP-dependent protein kinase
      (PKG). Our nanoflow ESI-TOF-MS analysis confirms that PKG mainly occurs as a 153
      kDa homodimer and is able to bind four cGMP molecules, which is in agreement with
      the known stoichiometry. Binding order and stoichiometry of cGMP, the non
      hydrolysable ATP analog beta,gamma-imidoadenosine 5'-triphosphate (AMPPNP) and
      Mn2+ for PKG were characterized as model for the active PKG-cGMP-ATP/Mg2+
      complex. Already in the absence of cGMP, a noncovalent complex between PKG and
      two molecules of AMPPNP could be observed by ESI-TOF-MS. Binding of AMPPNP to PKG
      was strongly enhanced by the addition of MnCl2 to the spray solution. This is in
      agreement with binding of AMPPNP/Mn2+ in the ATP binding pocket of PKG since all
      protein kinases require a metal ion to accompany ATP in the ATP-binding pocket
      for proper positioning of the beta and gamma phosphates. Additionally, this
      finding could imply that within the inactive conformation of PKG, the
      autoinhibition-domain, when in contact with the substrate-docking domain, does
      not block the entrance to the ATP-binding site. In the presence of cGMP, less of
      the fully saturated PKG-(cGMP)4(AMPPNP/Mn2+)2 complex was observed, suggesting
      that the PKG-ATP interaction is weakened in the active conformation of PKG.
      Additionally, limited proteolysis in combination with native-ESI MS showed to be
      a useful tool to study the contact regions on the PKG-dimer and also allowed the
      rapid determination of the overall autophosphorylation status of the protein.
      These measurements indicated that autophosphorylation mainly occurs within the
      first 80 aminoterminal residues and involves in total 3-4 phosphates per subunit.

PMID- 15465352
TI  - Characterization of noncovalent protein-ligand complexes and associated enzyme
      intermediates of GlcNAc-6-O-sulfotransferase by electrospray ionization FT-ICR
      mass spectrometry.
AB  - In this study, a GlcNAc-6-O-Sulfotransferase, NodST and its complexation with the
      substrate 3'-phosphoadenosine 5'-phosphosulfate (PAPS) and the inhibitor 3'
      phosphoadenosine 5'-phosphate (PAP) were studied using Fourier transform ion
      cyclotron resonance (FTICR) mass spectrometry. In addition, using isotopically
      labeled substrate, we have successfully confirmed a sulfated enzyme intermediate,
      which was predicted by the MS kinetic measurement. It is also shown that
      information regarding solution binding affinities can be obtained using
      electrospray ionization (ESI)-FTICR mass spectrometry. The relative binding
      constants, Kd(PAPS)/Kd(PAP), derived from the solution and gas phase were very
      similar, which suggests that the binding domain of this particular enzyme system,
      given known structures of other sulfotransferases, may be preserved during the
      transmission of the complex from solution to the gas phase.

PMID- 15465353
TI  - Further studies on the origins of asymmetric charge partitioning in protein
      homodimers.
AB  - Dissociation of gas-phase protonated protein dimers into their constituent
      monomers can result in either symmetric or asymmetric charge partitioning.
      Dissociation of alpha-lactalbumin homodimers with 15+ charges results in a
      symmetric, but broad, distribution of protein monomers with charge states
      centered around 8+/7+. In contrast, dissociation of the 15+ heterodimer
      consisting of one molecule in the oxidized form and one in the reduced form
      results in highly asymmetric charge partitioning in which the reduced species
      carries away predominantly 11+ charges, and the oxidized molecule carries away 4+
      charges. This result cannot be adequately explained by differential charging
      occurring either in solution or in the electrospray process, but appears to be
      best explained by the reduced species unfolding upon activation in the gas phase
      with subsequent separation and proton transfer to the unfolding species in the
      dissociation complex to minimize Coulomb repulsion. For dimers of cytochrome c
      formed directly from solution, the 17+ charge state undergoes symmetric charge
      partitioning whereas dissociation of the 13+ is asymmetric. Reduction of the
      charge state of dimers with 17+ charges to 13+ via gas-phase proton transfer and
      subsequent dissociation of the mass selected 13+ ions results in a symmetric
      charge partitioning. This result clearly shows that the structure of the dimer
      ions with 13+ charges depends on the method of ion formation and that the
      structural difference is responsible for the symmetric versus asymmetric charge
      partitioning observed. This indicates that the asymmetry observed when these ions
      are formed directly from solution must come about due either to differences in
      the monomer conformations in the dimer that exist in solution or that occur
      during the electrospray ionization process. These results provide additional
      evidence for the origin of charge asymmetry that occurs in the dissociation of
      multiply charged protein complexes and indicate that some solution-phase
      information can be obtained from these gas-phase dissociation experiments.

PMID- 15465354
TI  - Charge competition and the linear dynamic range of detection in electrospray
      ionization mass spectrometry.
AB  - An experimental investigation and theoretical analysis are reported on charge
      competition in electrospray ionization (ESI) and its effects on the linear
      dynamic range of ESI mass spectrometric (MS) measurements. The experiments
      confirmed the expected increase of MS sensitivities as the ESI flow rate
      decreases. However, different compounds show somewhat different mass spectral
      peak intensities even at the lowest flow rates, at the same concentration and
      electrospray operating conditions. MS response for each compound solution shows
      good linearity at lower concentrations and levels off at high concentration,
      consistent with analyte "saturation" in the ESI process. The extent of charge
      competition leading to saturation in the ESI process is consistent with the
      relative magnitude of excess charge in the electrospray compared to the total
      number of analyte molecules in the solution. This ESI capacity model allows one
      to predict the sample concentration limits for charge competition and the on-set
      of ionization suppression effects, as well as the linear dynamic range for ESI
      MS. The implications for quantitative MS analysis and possibilities for
      effectively extending the dynamic range of ESI measurements are discussed.

PMID- 15465355
TI  - Features of the ESI mechanism that affect the observation of multiply charged
      noncovalent protein complexes and the determination of the association constant
      by the titration method.
AB  - Several factors, attributable to the ESIMS mechanism, that can affect the
      assumptions of the titration method are examined: (1) The assumption that the
      concentrations in solution of the protein P, the ligand L, and the complex PL are
      proportional to the respective ion intensities observed with ESIMS, is examined
      with experiments in which ion intensities of two non-interacting proteins are
      compared with the respective concentrations. The intensities are found to be
      approximately proportional to the concentrations. The proportionality factors are
      found to increase as the mass of the protein is decreased. Very small proteins
      have much higher intensities. The results suggest that it is preferable to use
      only the intensity ratio of PL and P, whose masses are very close to each other
      when L is small, to determine the association constant KA in solution. (2) From
      the charge residue model (CRM) one expects that the solution will experience a
      very large increase of concentration due to evaporation of the precursor
      droplets, before the proteins P and PL are produced in the gas phase. This can
      shift the equilibrium in the droplets: P + L = PL, towards PL. Analysis of the
      droplet evaporation history shows that such a shift is not likely, because the
      time of droplet evolution is very short, only several micros, and the equilibrium
      relaxation time is much longer. (3) The droplet history shows that unreacted P
      and L can be often present together in the same droplet. On complete evaporation
      of such droplets L will land on P leading to PL and this effect will lead to
      values of KA that are too high. However, it is argued that mostly accidental,
      weakly bonded, complexes will form and these will dissociate in the clean up
      stages (heated transfer capillary and CAD region). Thus only very small errors
      are expected due to this cause. (4) Some PL complexes may have bonding that is
      too weak in the gas phase even though they have KA values in solution that
      predict high solution PL yields. In this case the PL complexes may decompose in
      the clean up stages and not be observed with sufficient intensity in the mass
      spectrum. This will lead to KA values that are too low. The effect is expected
      for complexes that involve significant hydrophobic interaction that leads to high
      stability of the complex in solution but low stability in the gas phase. The
      titration method is not suited for such systems.

PMID- 15465356
TI  - Alpha-synuclein: stable compact and extended monomeric structures and pH
      dependence of dimer formation.
AB  - The protein alpha-synuclein, implicated in Parkinson's disease, was studied by
      combining nano-electrospray ionization (N-ESI) mass spectrometry and ion
      mobility. It was found that both the charge-state distribution in the mass
      spectra and the average protein shape deduced from ion mobility data, depend on
      the pH of the spray solution. Negative-ion N-ESI of pH 7 solutions yielded a
      broad charge-state distribution from -6 to -16, centered at -11, and ion mobility
      data consistent with extended protein structures. Data obtained for pH 2.5
      solutions, on the other hand, showed a narrow charge-state distribution from -6
      to -11, centered at -8, and ion mobilities in agreement with compact alpha
      synuclein structures. The data indicated that there are two distinct families of
      structures: one consisting of relatively compact proteins with eight or less
      negative charges and one consisting of relatively extended structures with nine
      or more charges. The average cross section of a-synuclein at pH 2.5 is 33%
      smaller than for the extended protein sprayed from pH 7 solution. Significant
      dimer formation was observed when sprayed from pH 7 solution but no dimers were
      observed from the low pH solution. A plausible mechanism for aggregate formation
      in solution is proposed.

PMID- 15465357
TI  - MALDI-TOF-MS analysis of bacterial spores: wet heat-treatment as a new releasing
      technique for biomarkers and the influence of different experimental parameters
      and microbiological handling.
AB  - Short wet heat-treatment is presented as a new technique to release high-mass
      biomarkers to obtain strain-specific fingerprints of intact bacterial spores by
      matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS). Wet
      heat-treatment was applied for several minutes (3-30) by two techniques using
      either a screw-cap tube submerged in a glycerol bath at 120 degrees C or an
      Eppendorff-tube submerged in a water bath at 100 degrees C. Both techniques
      turned out to be successful for releasing high-mass biomarkers. The influence of
      different experimental parameters and microbiological handling on the peak
      pattern of the released high-mass biomarkers was studied. While the sporulation
      medium, the applied washing procedure, and the choice of matrix crucially
      influenced the peak pattern, other parameters like storage conditions were found
      to be insignificant. A protocol of optimized experimental conditions for MALDI-MS
      of wet heat-treated spores is presented.

PMID- 15465358
TI  - Bimetallic silver-gold clusters by matrix-assisted laser desorption/ionization.
AB  - Pure gold clusters (Aun+) were produced up to the cluster size of n = 100 by
      matrix-assisted laser desorption/ionization (MALDI). The mass spectrum of the
      resulting clusters showed alteration in the ion intensity at odd-even clusters
      size. On the other hand, intensity drops at cluster size predicted by the jellium
      model theory was also observed. Positively and negatively charged bimetallic
      silver-gold clusters were produced under MALDI conditions from the mixture of
      HAuCl4/silver trifluoroacetate and the 2-(4-hydroxyphenylazo)benzoic acid (HABA)
      matrix. A linear correlation was found between the intensity ratio of AunAgm+ to
      Au(n+1)Ag(m-1)+ cluster ions and the molar ratio of the gold to silver salt. It
      was observed that the composition and the distribution of the clusters can be
      varied with the molar ratio of the silver and gold salts. It was also found that
      the resulting cluster sizes obey the lognormal distribution.

PMID- 15465359
TI  - Proposed mechanisms for the fragmentation of doubly allylic alkenamides (tingle
      compounds) by low energy collisional activation in a triple quadrupole mass
      spectrometer.
AB  - Tingle compounds are a class of alkenamides with organoleptic properties that
      include a numbing or a pins and needles effect that is generally perceived on the
      lips and in the mouth when consumed. They occur in nature in a number of
      botanical species. Spilanthol and Pellitorine are important examples of tingle
      compounds. A number of homologs and analogs were synthesized to study the effect
      of chain length, double bond location, and amide moiety on the tingle effect.
      This also provided the opportunity to study the behavior of these compounds in
      the collision cell of a triple quadrupole mass spectrometer. The doubly allylic
      2E,6Z-alkenamides, which made up the largest class studied, fragmented in a
      characteristic way to produce a distonic radical cation and a cyclopropene
      cation. Mechanisms for the formation of these ions are proposed. The mechanisms
      are supported by energy-resolved mass spectrometric data, the analysis of
      deuterated analogs and homologs that are not doubly allylic, and exact mass
      measurements. Exceptions to the proposed mechanisms are also presented. These
      data represent the first attempt to apply mechanistic principles to the product
      ions observed in the MS/MS spectra of these compounds. The authors believe the
      results of this study will facilitate the identification of these and similar
      compounds and contribute to the fundamental understanding of the behavior of
      alkenamides in the collision cell of a triple quadrupole mass spectrometer.

PMID- 15465360
TI  - On-line single droplet deposition for MALDI mass spectrometry.
AB  - A single droplet generator was coupled with a rotating ball inlet matrix-assisted
      laser desorption/ionization (MALDI) time of flight (TOF) mass spectrometer.
      Single droplets with 100 picoliter volume were ejected by a piezoelectric
      actuated droplet generator and deposited onto a matrix-coated rotating stainless
      steel ball at atmospheric pressure. The single droplet deposit was transported to
      the vacuum side of the instrument where ionization was accomplished using a UV
      pulsed laser. Using this on-line interface, it was possible to obtain protonated
      molecule signal from as little as 10 fmol analyte.

PMID- 15465361
TI  - Generating protein sequence tags by combining cone and conventional collision
      induced dissociation in a quadrupole time-of-flight mass spectrometer.
AB  - The goal of proteomics research is to be able to identify and quantify the vast
      numbers of proteins within an organism or tissue. "Top-down" methods address this
      goal without the need for proteolytic digestion prior to mass analysis. We report
      here an approach for top-down protein identification that has been implemented on
      a commercially available, unmodified Qq-TOF mass spectrometer. Intact protein
      molecular ions first undergo cone fragmentation in the electrospray inlet.
      Conventional MS/MS is then performed on a mass selected cone fragment using CID
      in the Qq interface of the Qq-TOF mass spectrometer to generate a sequence tag
      through a pseudo-MS3 experiment. Seven proteins varying in molecular weight
      between 11 and 66 kDa were chosen to demonstrate applicability of method. After
      the molecular weight of the intact protein was determined, the cone voltage was
      varied to induce fragmentation. Cone fragment ions were then further dissociated
      using conventional CID, and the resulting MS/MS spectra were processed and
      analyzed for sequence tags. Sequence tags were easily identified from a MS/MS
      spectrum of a cone induced fragment ion both manually and through a de novo
      sequencing program included in the software associated with the mass
      spectrometer. Sequence tags were subjected to database searching using the
      PeptideSearch program of EMBL, and all protein sequence tags gave unambiguous
      search results. In all cases, sequence tags were found to originate from the n-
      and/or c-termini of the proteins.

PMID- 15465362
TI  - Modeling the resolution and sensitivity of FAIMS analyses.
AB  - Field asymmetric waveform ion mobility spectrometry (FAIMS) is rapidly gaining
      acceptance as a robust, versatile tool for post-ionization separations prior to
      mass-spectrometric analyses. The separation is based on differences between ion
      mobilities at high and low electric fields, and proceeds at atmospheric pressure.
      Two major advantages of FAIMS over condensed-phase separations are its high speed
      and an ion focusing effect that often improves sensitivity. While selected
      aspects of FAIMS performance are understood empirically, no physical model
      rationalizing the resolving power and sensitivity of the method and revealing
      their dependence on instrumental variables has existed. Here we present a first
      principles computational treatment capable of simulating the FAIMS analyzer for
      virtually any geometry (including the known cylindrical and planar designs) and
      arbitrary operational parameters. The approach involves propagating an ensemble
      of ion trajectories through the device in real time under the influence of
      applied asymmetric potential, diffusional motion incorporating the high-field and
      anisotropic phenomena, and mutual Coulomb repulsion of ionic charges.
      Calculations for both resolution and sensitivity are validated by excellent
      agreement with measurements in different FAIMS modes for ions representing
      diverse types and analyte classes.

PMID- 15465363
TI  - Electrospray ionization tandem mass spectrometry of glycerophosphoethanolamine
      plasmalogen phospholipids.
AB  - Collision-induced dissociation (CID) of the [M + H]+ of glycerophospholipids
      typically results in abundant fragment ions that are related to the polar head
      group or loss of the polar head group. An exception to this general rule occurs
      for glycerophosphoethanolamines (GPEtn), which are a class of phospholipids that
      can have an acyl, 1-O-alkyl, or 1-O-alk-1'-enyl group as a substituent at the sn
      1 position. The CID of the [M + H]+ of diacyl-GPEtn typically results in the
      expected loss of the phosphoethanolamine head group (141 Da). Therefore, constant
      neutral loss of 141 Da has been used as a diagnostic tool for the determination
      of GPEtn species in complex lipid mixtures. One disadvantage in using constant
      neutral loss of 141 Da in order to determine GPEtn content in lipid mixtures is
      that plasmalogen GPEtn does not undergo neutral loss of phosphoethanolamine to
      the same extent as diacyl-GPEtn. The current studies have used positive ion mode
      electrospray tandem mass spectrometry to study the collision-induced dissociation
      of various GPEtn plasmalogens present in the phospholipid membranes of human
      neutrophils. The CID of the [M + H]+ of plasmalogen GPEtn resulted in two
      prominent fragment ions; one that was characteristic of the sn-1 position and one
      that was characteristic of the sn-2 position. These two ions were used to detect
      specific molecular species of GPEtn containing esterified arachidonate
      (precursors of m/z 361) present in the human neutrophil.

PMID- 15465365
TI  - Does the modern concept of 'best medical therapy' render carotid surgery
      obsolete?

PMID- 15465364
TI  - Stereoselectivity in the collision-activated reactions of gas phase salt
      complexes.
AB  - The collision-activated dissociations (CAD) of gas phase salt complexes composed
      of chiral ions were studied in a quadrupole ion trap mass spectrometer. Because
      both partners in the salt are chiral, diastereomeric complexes can be formed
      (e.g., RR, RS). Two general types of complexes were investigated. In the first,
      the complex was composed of deprotonated binaphthol and a chiral bis
      tetraalkylammonium dication. CAD of these complexes leads to the transfer of a
      proton or an alkyl cation to the binaphtholate leading to a singly-charged
      tetraalkylammonium cation. During CAD, diastereomeric complexes give
      significantly different product distributions indicating reasonable
      stereoselectivity in the process. In the second system, the complexes involved a
      peptide dianion and a chiral tetraalkylammonium cation. These systems may be
      viewed as very simple models for the interactions of peptides/proteins with small
      chiral molecules. Again, stereoselectivity was evident during CAD, but the extent
      was dependent on the nature of the peptide and not observable in some cases. To
      better understand the structural features needed to achieve stereoselectivity in
      gas phase salt complexes, representative transition states were modeled
      computationally. The results suggest that it is critical for the asymmetry of the
      nucleophile (i.e., anion) to be well represented in the vicinity of its reactive
      center.

PMID- 15465366
TI  - Meta-analysis of allograft bypass grafting to infrapopliteal arteries.
AB  - OBJECTIVE: To determine graft patency and limb preservation after allograft
      bypass grafting to infrapopliteal arteries for different allograft materials.
      DESIGN: Meta-analysis of case series that used survival analysis to describe
      outcomes. METHODS: Studies published from 1982 through 2003 were identified from
      electronic databases and pertinent original articles. Four series of
      cryopreserved arterial allografts, 10 series of cryopreserved vein allografts,
      three series of cold-storaged vein allografts, and 16 series of umbilical-cord
      vein allografts were included in separate random-effects meta-analyses. RESULTS:
      A graphical display of pooled survival curves of graft patency showed cold
      storaged veins to have the best outcome in the first 4 years, followed by
      cryopreserved arteries, umbilical-cord veins, and cryopreserved veins. The
      respective 5-year pooled patency were 24, 21, 30, and 19%. For foot preservation,
      the best outcome was achieved with cryopreserved arteries followed by
      cryopreserved veins, umbilical-cord veins, and cold-storaged veins. A reference
      meta-analysis of polytetrafluoroethlylene grafts occupied the top position for
      graft patency and the second position for foot preservation. CONCLUSION: In leg
      revascularisation for critical ischaemia, graft patency is poor for allografts
      generally, but using peripheral allografts in repeat attempts at
      revascularisation is a valid strategy to prevent major amputation. A role for
      umbilical-cord vein allografts remains uncertain.

PMID- 15465367
TI  - Improvement in deep vein haemodynamics following surgery for varicose veins.
AB  - OBJECTIVE: o analyse the effect of superficial and perforating veins surgery on
      deep vein incompetence. METHODS: During a six-month period between 2000 and 2001
      24 patients (32 limbs) with chronic venous insufficiency (CVI) were treated. They
      were selected because they had varicose veins and proximal deep vein incompetence
      with photoplethysmography (PPG) venous refilling time (VRT) <15 s with a below
      knee tourniquet, and a femoral or popliteal vein reflux time (RT) >1.5 s on
      duplex ultrasound. The group was divided according to aetiology into 21 legs with
      primary (Ep) and 11 with secondary CVI (Es). All patients underwent removal of
      varices with stripping of the saphenous veins, if appropriate. In 21 cases
      subfascial endoscopic perforating vein surgery (SEPS) was performed to ligate
      incompetent perforating veins. RESULTS: The average VRT for the entire group
      increased from 9.8 s before to 15 s after operation (p<0.001, paired t test). In
      the Ep group the average VRT increased from 11 to 18 s (p<0.001, paired t test),
      in Es group from 7.5 to 10 s (p>0.001, paired t test). Duplex ultrasonography
      before surgery showed femoral vein incompetence in 28 and the popliteal
      incompetence in 26 cases. The average femoral vein RT was 1.9 s before and 1.4 s
      after surgery (p<0.001, paired t test). The femoral RT in the Ep group decreased
      from 1.9 to 1.3 s (p<0.001, paired t test) and in the Es group from 1.9 to 1.6 s
      (N.S.). In the popliteal vein, RT was 1.8 s before, and 1.3 s after surgery
      (p<0.001, paired t test). The RT in the Ep group shortened from 1.8 to 1.1 s
      (p<0.001 paired t test) and in the Es group from 1.9 to 1.5 s (N.S.). CONCLUSION:
      Surgical treatment of varicose veins and of calf perforators results in reduced
      deep vein reflux. The improvement is most marked in cases of primary venous
      insufficiency.

PMID- 15465368
TI  - Immunocytochemical characterisation of the inflammatory cell infiltrate of
      varicose veins.
AB  - OBJECTIVES: To characterise the inflammatory cell infiltrate in varicose vein
      wall, and its relationship to the valve complex. DESIGN: A comparative study of
      the distribution of inflammatory cells in normal and varicose vein. MATERIALS:
      Specimens of proximal human long saphenous vein were obtained from patients with
      duplex Doppler confirmed long saphenous vein reflux (n=14). Control vein was
      obtained from patients undergoing coronary artery bypass without clinical
      evidence of venous insufficiency (n=6). Longitudinal 7 microm frozen sections of
      vein, displaying valve, were prepared. METHODS: Using immunohistochemistry, T
      lymphocytes (CD3), macrophage/monocytes (CD68), neutrophils (CD15s) and mast
      cells (anti-mast cell tryptase) were identified. The number of cells per unit
      length vein were counted using light microscopy. RESULTS: There were
      significantly more mast cells and macrophage/monocytes in varicose vein as
      compared to control. There was a non-significant trend towards more T-lymphocytes
      in varicose vein. Few neutrophils were present in varicose or normal vein. The
      distribution of inflammatory cells with respect to the valve was not found to be
      significant. CONCLUSIONS: Varicose veins display a greater inflammatory cell
      infiltrate than normal vein. The key role of macrophage/monocytes and mast cells
      in tissue damage and remodelling should stimulate further research into whether
      they play a significant role in the development of chronic venous insufficiency.

PMID- 15465370
TI  - Is routine intravascular shunting necessary for carotid endarterectomy in
      patients with contralateral occlusion? A review of 5-year experience of carotid
      endarterectomy with local anaesthesia.
AB  - OBJECTIVES: Endarterectomy of a stenotic internal carotid artery in the presence
      of contralateral carotid occlusion (CCO) is often assessed as a high-risk
      procedure. We have assessed the requirement for shunting in patients with CCO
      operated under local anaesthetic. MATERIALS AND METHODS: Between 1998 and 2003,
      429 patients (319 males and 110 females, mean age 65.7+/-6.2, range 48-84)
      underwent 500 carotid endarterectomies under local anaesthetic with awake
      neurological testing. Fifty-five patients (12.8%) had CCO. Preoperative risk
      factors, intra- and postoperative events were noted and analyzed. Short-term and
      mid-term follow-up (mean 16.4+/-5.8 months, range 3-38 months) was also recorded.
      RESULTS: The rate of shunting in patients with or without CCO (10.9% vs. 9.1%)
      was not significantly different. Stroke rates for CCO and non-CCO groups were 3.6
      and 0.5%, respectively. Only the presence of preoperative cerebral infarction
      increased the risk of stroke. Patients that needed shunting were found to have
      significantly higher overall rate of adverse events, mortality and stroke.
      CONCLUSIONS: Routine use of intravascular shunting for a stenotic carotid artery
      with contralateral occlusion may not be necessary. The choice of using a shunt is
      safe when made intraoperatively by assessing the neurological status of the
      patient continuously. This requires expertise and strong cooperation between the
      anaesthesiologist and the surgical teams.

PMID- 15465369
TI  - Venous hypertension, inflammation and valve remodeling.
AB  - OBJECTIVES: To identify possible mechanisms for destruction of valves in chronic
      venous hypertension and the results of treatment with an anti-inflammatory
      micronized purified flavonoid fraction. MATERIAL AND METHODS: The saphenous vein
      valves in a rat model of venous hypertension caused by a femoral arterial-venous
      fistula were studied. Studies included femoral venous pressure, valve morphology,
      femoral venous reflux and selected molecular inflammatory markers as examined by
      immunohistochemistry. The effects of treatment with the anti-inflammatory
      micronized purified flavonoid fraction (S 5628, Servier, 50 and 100 mg/kg/day)
      were investigated. RESULTS: The femoral venous pressure was elevated close to
      arterial values for a period of 3 weeks. We then examined the morphology of the
      veins and selected molecular inflammatory markers were assessed. The results show
      that in this model venous reflux develops in response to venous hypertension.
      This can be inhibited by the administration of the anti-inflammatory micronized
      purified flavonoid fraction (S 5628, Servier, 50 and 100 mg/kg/day). The valve
      becomes incompetent by a combination of venous dilation and shortening of the
      valve leaflets. This is not inhibited by treatment with S 5628. The valve
      leaflets are infiltrated with granulocytes, monocytes and T-lymphocytes, and the
      endothelial cells express enhanced levels of P-selectin and ICAM-1. Cells in the
      valves are subject to extensive apoptosis although no enhancement of MMP 2,9
      expression could be detected at the three-week time point examined in this study.
      CONCLUSIONS: These results indicate that in this model chronic elevation of
      venous pressure is associated with an inflammatory reaction in venous valves, a
      process that may lead to their dysfunction, reflux, and upstream elevation of
      venous pressure. These effects are mitigated by the anti-inflammatory micronized
      purified flavonoid fraction in a dose dependent manner.

PMID- 15465371
TI  - The relationship between plasma MMP-1, -7, -8 and -13 levels and embolic
      potential during carotid endoluminal intervention.
AB  - BACKGROUND: Patients undergoing carotid endoluminal intervention are at risk of
      embolic stroke even with the use of distal protection devices. Matrix
      metalloproteinases (MMPs) have been implicated as a causal factor in plaque
      instability leading to spontaneous embolisation. We investigated whether plasma
      MMP levels correlated with the embolisation during carotid endoluminal
      intervention. METHODS: Thirty circumferentially intact carotid endarterectomy
      specimens were subjected to a standardised angioplasty procedure in a pulsatile
      ex vivo model. Emboli collected in a series of distal filters were counted and
      sized. Plasma samples were collected pre-operatively and analysed for MMP-7 and
      MMP-8 levels using Western immunoblotting. MMP-1 and MMP-13 levels were
      determined using ELISA. Emboli number and maximum size were correlated with
      plasma levels of the MMPs using Spearmans rank. RESULTS: Total MMP-8 levels were
      related to maximum embolus size (r=0.442, p=0.005) but not emboli number
      (r=0.342, p=0.052). MMP-1, -7 and -13 were not correlated with either emboli
      number or with maximum embolus size. CONCLUSION: Pre-operative plasma MMP-8
      levels are related to the size of emboli from plaques during carotid endovascular
      intervention. Further in vivo studies need to be performed to assess the
      importance of this finding. There is potential for development of plasma markers
      to identify those patients at greater risk of embolic stroke during carotid
      endoluminal intervention.

PMID- 15465372
TI  - Long-term outcome following thrombembolectomy in the upper extremity.
AB  - OBJECTIVES: To evaluate short- and long-term mortality and morbidity in patients
      that were treated for acute upper extremity ischemia. DESIGN: Single center
      retrospective study. PATIENTS: A consecutive series of 148 patients who were
      admitted with a diagnosis of acute ischemia of the upper extremity during an 11
      year period. METHODS: All charts were reviewed retrospectively and 96% of all
      survivors participated in clinical follow-up. RESULTS: The median age was 78
      years and 64% of patients were females. The 30-day mortality was 8% and the
      overall 5-year survival 37%. The observed mortality during the follow-up period
      was significantly higher than expected. Survival was not significantly different
      in patients who received anticoagulant drugs following discharge from the
      hospital. The duration of ischemia did not significantly influence long-term arm
      function. CONCLUSIONS: Acute embolic episodes in the upper extremity primarily
      occur in elderly and the peri-operative mortality is high. Mortality following
      discharge from the hospital remains significantly higher than that of the
      background population.

PMID- 15465373
TI  - Comparison between duplex scanning and angiographic findings in the evaluation of
      functional iliac obstruction in top endurance athletes.
AB  - OBJECTIVE: Review of a 10 year-experience, to evaluate the efficacy of pre
      operative investigations in the detection of external iliac artery (EIA)
      endofibrosis in top endurance athletes. DESIGN: Retrospective study. MATERIALS:
      From September 1995 to March 2004, 13 highly-trained athletes (all men, mean age
      32.3 years) underwent surgery for disease involving 14 lower limbs (11 left, one
      right, one bilateral). METHODS: We compared ultrasound scan (US) and digital
      subtraction angiography (DSA) data, at rest and at hip flexion with intra
      operative findings for all 14 lower limbs. We analyzed the presence of stenosis
      in the external and common iliac arteries, the presence of psoas muscle arteries
      and the presence of excessive EIA length. RESULTS: In the affected limbs, before
      treatment, the mean ankle brachial index (ABI) at rest was 0.98 compared with
      0.56 after exercise, p=0.0001. The sensitivities of the US vs DSA examination in
      the detection of external and common iliac artery stenosis were, respectively,
      84.6 and 53.8% vs 53.8 and 12.5%. The muscle psoas artery was detected by DSA
      with a sensitivity of 57.1 and 100% specificity. For the detection of excessive
      EIA length, the sensitivity of US was 85.7% with 57.1% specificity. CONCLUSIONS:
      A fall of ABI after exercise proves the presence of a significant stenosis in
      symptomatic athletes. Color coded duplex ultrasonography is recommended for non
      invasive imaging of suspected endofibrotic stenosis in young athletes, since it
      detects reliably both stenosis and elongation of iliacal arteries.

PMID- 15465374
TI  - Early post-operative glucose levels are an independent risk factor for infection
      after peripheral vascular surgery. A retrospective study.
AB  - OBJECTIVE: To evaluate whether hyperglycaemia in the first 48 h after
      infrainguinal vascular surgery is a risk factor for post-operative infection,
      independent from factors associated with insulin resistance and surgical stress.
      DESIGN: Retrospective cohort study. PATIENTS AND METHODS: Patients who underwent
      infrainguinal vascular surgery in our hospital between March 1998 and March 2003
      were included. Glucose values until 48 h after surgery were retrieved from
      laboratory reports. Post-operative infections, treated with antibiotics, during
      hospital stay were scored until 30 days after surgery. Data were analysed with
      univariate and multivariate logistic regression analyses. RESULTS: At least one
      post-operative glucose value was retrieved for 211/275 (77%) patients. The
      incidence of post-operative infections was 84/275 (31%). When corrected for
      factors associated with insulin resistance and surgical stress, post-operative
      glucose levels were found to be an independent risk factor for post-operative
      infections (odds ratio top quartile versus lowest quartile: 5.1; 95% confidence
      interval: 1.6-17.1; P=0.007). CONCLUSION: Post-operative glucose levels appear to
      be an independent risk factor for infections after infrainguinal vascular
      surgery. This finding requires confirmation in a prospective study.

PMID- 15465375
TI  - Sutureless anastomoses of small and medium sized vessels by medical adhesive.
AB  - PURPOSE: Using an animal model we have assessed sutureless anastomoses. METHODS:
      The two cut ends of the rabbit common carotid artery were sutured by three
      stitches with a 120 degrees interval circumferentially, then two optional threads
      were pulled horizontally and 0.1 ml adhesive was smeared on the attached surface
      of the two ends. The three stitches were removed after completion of anastomosis.
      The burst pressure of the anastomosis was measured and compared with that of a
      traditional sutured artery. RESULTS: The glued anastomosis was associated with: a
      shorter completion time (8.25+/-6.34 min vs. 20.67+/-14.24 min, P<0.01), less
      bleeding (3.17+/-9.04 ml vs. 11.04+/-16.28 ml, P<0.01), and equivalent patency
      (93.8 vs. 87.5%, P>0.05). The sutureless anastomosis was associated with less
      intimal thickening (decreased by 31.4, 24.5, 23.9 and 31.9%, P<0.01 compared with
      the traditional suture group at 1, 2, 4 and 12 weeks, respectively). CONCLUSION:
      Glued anastomoses provides an effective, simple and feasible way for anastomosing
      small or medium caliber vessels. This technique may reduce intimal injury.

PMID- 15465376
TI  - Effect of suprarenal stent struts on the renal artery with ostial calcification
      observed on CT virtual intravascular endoscopy.
AB  - OBJECTIVES: The behaviour of stent struts crossing the renal ostia and their
      effect on renal ostia configuration is not well understood. The study aims to
      investigate whether suprarenal stent struts affect the morphological change of
      the renal artery with ostial calcification observed on CT virtual intravascular
      endoscopy. METHODS: Nine patients with abdominal aortic aneurysms undergoing
      suprarenal fixation of stent grafts were included in the study. All patients
      received a Zenith endovascular graft with uncovered suprarenal components placed
      above the renal arteries. Renal ostial calcification and configuration of stent
      wires crossing the renal ostium were characterized in each patient and maximal
      transverse and longitudinal diameters of the renal ostia were measured on virtual
      endoscopy pre- and post-stent grafting. RESULTS: There were altogether 17 renal
      ostia assessed with one patient having atrophic left kidney and no renal ostium
      being observed. Ostial calcification was found in five of the left renal ostia
      and five of the right renal ostia with one patient having bilateral ostial
      calcification. There was no significant difference between the renal ostial
      diameters measured pre- and post-stent grafting (p>0.05). Suprarenal stent struts
      were found to cross the renal ostia in various configurations observed on virtual
      endoscopy. All of the renal arteries were patent on follow-up CT scans after
      suprarenal fixation without stenosis or occlusion being observed. One patient
      with atrophic left renal artery developed renal failure following suprarenal
      stent grafting and received renal dialysis, while in the remaining cases median
      serum creatinine level did not change significantly. CONCLUSIONS: Suprarenal
      stent struts did not significantly affect the renal ostia with ostial
      calcification in terms of the diameter measurements and renal function. Further
      studies deserve to investigate the long-term effect of stent struts on the renal
      artery in terms of cross-sectional area reduction caused by stent wires and
      ostial calcification.

PMID- 15465377
TI  - Does immediate operation for symptomatic non-ruptured abdominal aortic aneurysm
      compromise outcome?
AB  - Background. The optimum timing of surgery for acutely symptomatic abdominal
      aortic aneurysm (AAA) remains a clinical dilemma: should symptomatic aneurysm be
      operated on urgently for fear of impending rupture, or should there be a period
      of preoperative evaluation to optimise the patient's medical co-morbidity, with a
      consequent delay in surgery? Method. Ninety-five patients were diagnosed with
      acutely symptomatic AAA (back pain, abdominal pain or a tender aneurysmal aorta)
      between 1995 and 2001 and included in a retrospective case-cohort study. The in
      hospital mortality rates for patients undergoing early surgery (within 24h of
      presentation) were compared to those of patients whose surgery had been delayed
      to allow further evaluation. Results. Of 95 patients with an acutely symptomatic
      AAA, 70 had surgery within 24h of admission. The remaining 25 underwent planned
      delayed surgery after a median of (range) three (2-17) days. The reasons for
      delay to AAA repair were primarily to allow further cardiorespiratory assessment
      and radiological imaging. In the early surgery group, there were six
      postoperative deaths (9%); in the group who were to have delayed surgery, there
      were three (12%) deaths (P=0.694). Conclusion. Early operation for acutely
      symptomatic AAA, in selected patients, is not associated with an excessive
      mortality rate compared to delayed operation.

PMID- 15465378
TI  - The role of Chlamydia pneumoniae in human aortic disease-a hypothesis revisited.
AB  - BACKGROUND: The role of Chlamydia pneumoniae in the pathogenesis of aortic
      aneurysm is controversial. We investigated the presence of C. pneumoniae in
      tissue samples excised from patients and controls. METHODS: Aortic wall specimens
      were obtained from 17 patients with acute Stanford type A aortic dissection, 25
      patients with thoracic aortic aneurysms (TAA) and 23 patients with abdominal
      aortic aneurysms (AAA). Eighty-three tissue samples of 73 control patients free
      of aortic disease were obtained either at surgery or autopsy. The presence of
      Chlamydia subspecies DNA (sequences specific for all known Chlamydiaceae) and DNA
      of C. pneumoniae, C. trachomatis and C. psittaci were assessed by a validated
      highly sensitive and specific real time polymerase chain reaction (PCR) analysis.
      Atherosclerotic risk factors were assessed in all patients. RESULTS: We failed to
      detect C. pneumoniae and C. psittaci-DNA in any of the 148 vessel specimens. C.
      trachomatis-DNA was detected in 1/65 patients and in none of 83 controls
      (P=0.43). Chlamydia subspecies DNA was found in samples of eight cases and in one
      control (P=0.01), however, no significant differences were found between the
      subgroups aortic dissection (P=0.09), TAA (P=0.99) and AAA (P=0.15) and
      respective controls. CONCLUSIONS: C. pneumoniae does not play a clinically
      relevant role in acute and chronic aortic disease. The impact of other organisms
      of the family Chlamydiaceae needs further evaluation.

PMID- 15465379
TI  - Detection and localization of periodontopathic bacteria in abdominal aortic
      aneurysms.
AB  - OBJECTIVES: We examined a possible link between periodontal disease and abdominal
      aortic aneurysm (AAA) by studying resected aneurysmal specimens from AAA patients
      for the presence of periodontopathic bacteria. DESIGN: Prospective case control
      study. MATERIAL AND METHODS: Thirty-two AAA patients were enrolled in the study.
      Periodontitis was classified according to the probing depth of periodontal
      pocket. Thirty-two aneurysmal walls, 16 mural thrombi, 5 atherosclerotic
      occlusive aorta and 5 control arterial tissue, were examined for 7 periodontal
      bacteria using polymerase chain reaction (PCR) method. The localization of the
      bacteria in the aneurysmal/atherosclerotic wall was determined by
      thromboendarterectomy. RESULTS: All patients had periodontal disease, and most
      cases were severe. PCR examination of the aneurysmal specimens showed that 86%
      were positive for periodontal bacterial DNA. No bacteria were detected in the
      control specimens. The bacteria were found in both the intimal/medial layer and
      the adventitial layer of the aneurysmal wall but only in intimal/medial layer of
      the atherosclerotic occlusive aorta. CONCLUSION: Periodontopathic bacteria were
      present in a high percentage of specimens of diseased arteries from AAA patients
      and were found throughout the whole aneurysmal wall. These bacteria may play a
      role in the development of AAAs and/or contribute to weakening the aneurysmal
      wall.

PMID- 15465380
TI  - Arterioureteric fistula: successful treatment of two cases.

PMID- 15465381
TI  - Recovery of renal function after 3 months of dialysis in a patient with
      atherosclerotic renovascular disease following aortoiliac bypass and left renal
      artery reimplantation.

PMID- 15465382
TI  - Mycotic peripheral aneurysms and intracerebral abscesses secondary to infective
      endocarditis.

PMID- 15465383
TI  - Regarding "The effect of long saphenous vein stripping on deep venous reflux" by
      MacKenzie RK, Allan PL, Ruckley CV, and Bradbury AW. Eur J Vasc Endovasc Surg 28,
      104-107 (2004).

PMID- 15465384
TI  - Regarding 'Reflux Elimination Without any Ablation or Disconnection of the
      Saphenous Vein. A Haemodynamic Model for Venous Surgery' and 'Durability of
      Reflux-elimination by a Minimal Invasive CHIVA Procedure on Patients with
      Varicose Veins. A 3-year Prospective Case Study'.

PMID- 15465385
TI  - Re: Interposition vein cuff and intimal hyperplasia: an experimental study
      (Ducasse et Al.; Eur J Vasc Endovasc Surg 2004; 27: 617-21).

PMID- 15465386
TI  - Double-joint PCR: a PCR-based molecular tool for gene manipulations in
      filamentous fungi.
AB  - Gene replacement via homologous double crossover in filamentous fungi requires
      relatively long (preferentially >0.5 kb) flanking regions of the target gene. For
      this reason, gene replacement cassettes are usually constructed through multiple
      cloning steps. To facilitate gene function studies in filamentous fungi avoiding
      tedious cloning steps, we have developed a PCR-assisted DNA assembly procedure
      and applied it to delete genes in filamentous fungi. While the principle of this
      procedure is essentially the same as other recently reported PCR-based tools, our
      technique has been effectively used to delete 31 genes in three fungal species.
      Moreover, this PCR-based method was used to fuse more than 10 genes to a
      controllable promoter. In this report, a detailed protocol for this easy to
      follow procedure and examples of genes deleted or over-expressed are presented.
      In conjunction with the availability of genome sequences, the application of this
      technique should facilitate functional characterization of genes in filamentous
      fungi. To stream line the analysis of the transformants a relatively simple
      procedure for genomic DNA or total RNA isolation achieving approximately 100
      samples/person/day is also presented.

PMID- 15465387
TI  - Two NADPH oxidase isoforms are required for sexual reproduction and ascospore
      germination in the filamentous fungus Podospora anserina.
AB  - NADPH oxidases are enzymes that produce reactive oxygen species (ROS) using
      electrons derived from intracellular NADPH. In plants and mammals, ROS have been
      proposed to be second messengers that signal defence responses or cell
      proliferation. By inactivating PaNox1 and PaNox2, two genes encoding NADPH
      oxidases, we demonstrate the crucial role of these enzymes in the control of two
      key steps of the filamentous fungus Podospora anserina life cycle. PaNox1 mutants
      are impaired in the differentiation of fruiting bodies from their progenitor
      cells, and the deletion of the PaNox2 gene specifically blocks ascospore
      germination. Furthermore, we show that PaNox1 likely acts upstream of PaASK1, a
      MAPKKK previously implicated in stationary phase differentiation and cell
      degeneration. Using nitro blue tetrazolium (NBT) and diaminobenzidine (DAB)
      assays, we detect a regulated secretion of both superoxide and peroxide during P.
      anserina vegetative growth. In addition, two oxidative bursts are shown to occur
      during fruiting body development and ascospore germination. Analysis of mutants
      establishes that PaNox1, PaNox2, and PaASK1, as well as a still unknown
      additional source of ROS, modulate these secretions. Altogether, our data point
      toward a role for NADPH oxidases in signalling fungal developmental transitions
      with respect to nutrient availability. These enzymes are conserved in other
      multicellular eukaryotes, suggesting that early eukaryotes were endowed with a
      redox network used for signalling purposes.

PMID- 15465388
TI  - Identification and complementation of abnormal hyphal branch mutants ahbA1 and
      ahbB1 in Aspergillus nidulans.
AB  - Branching generates new axes of polar growth in filamentous fungi and is critical
      for development, reproduction, and pathogenicity. To investigate branching we
      screened an Aspergillus nidulans temperature-sensitive mutant collection for
      abnormal hyphal branch (ahb) mutants. We identified two mutants, ahbA1, which
      showed reduced branching relative to wild type at restrictive temperature, and
      ahbB1, which showed increased branching relative to wild type at restrictive
      temperature. Both mutants also showed abnormal conidiophore development at
      restrictive temperature. The ahbA1 hypobranching mutant showed defects in nuclear
      division and hydroxyurea resistance. Complementation and sequencing showed that
      ahbA1 is a previously identified allele of the cell cycle regulator nimX. The
      ahbB1 hyperbranching mutant had an increased number of nuclei, was osmotically
      remedial and Calcofluor resistant. The ahbB gene is predicted to encode a novel
      protein that has homologues exclusively in filamentous fungi. The C-terminal
      domain of the predicted AhbB protein showed homology with the heme-binding domain
      of a cytochrome P450 protein and sequencing of the ahbB1 mutant allele showed
      that the lesion lies just before this putative heme-binding domain. The ahbB1
      mutant showed increased sensitivity to the ergosterol biosynthesis inhibitor
      imidazole. Our results suggest a link between nuclear division and branching and
      a possible role for membrane synthesis in branching.

PMID- 15465389
TI  - Turgor regulation in hyphal organisms.
AB  - Turgor regulation in two saprophytic hyphal organisms was examined directly with
      the pressure probe technique. The ascomycete Neurospora crassa, a terrestrial
      fungi, regulates turgor after hyperosmotic treatments when growing in a minimal
      medium containing K(+), Mg(2+), Ca(2+), Cl(-), and sucrose. Turgor recovery by N.
      crassa after hyperosmotic treatment is concurrent with changes in ion transport:
      hyperpolarization of the plasma membrane potential and a decline in transmembrane
      ion conductance. In contrast the oomycete Achlya bisexualis, a freshwater hyphal
      organism, does not regulate turgor after hyperosmotic treatment, although small
      transient increases in turgor were occasionally observed. We also monitored
      turgor in both organisms during hypoosmotic treatment and did not observe a
      turgor increase, possibly due to turgor regulation. Both hyphal organisms grow
      with similar morphologies, cellular expansion rates and turgor (0.4-0.7 MPa), yet
      respond differently to osmotic stress. The results do not support the assumption
      of a universal mechanism of tip growth driven by cell turgor.

PMID- 15465390
TI  - Efficient gene silencing by expression of double stranded RNA in Neurospora
      crassa.
AB  - In Neurospora crassa, sequence-specific inhibition of endogenous genes can be
      induced by the introduction of transgenic DNA homologous to the target gene,
      through the mechanism of post-transcriptional gene silencing (PTGS) known as
      quelling. The application of this strategy to inactivate genes in N. crassa has,
      to date, been restricted by a limited silencing efficiency and instability of the
      silenced phenotype. In this study we show that the use of constructs that express
      hairpin double stranded RNA (dsRNA) permits efficient gene silencing by-passing
      limiting events in the quelling triggering process occurring upstream of dsRNA
      production. We found that silenced strains expressing a hairpin RNA displayed
      higher phenotypic stability compared with quelled strains. Moreover, we show that
      gene silencing can be modulated by expressing the double stranded RNA from an
      inducible promoter. Together these results make this method suitable for
      producing hypomorphic mutants in N. crassa.

PMID- 15465391
TI  - A comparison of the nature and abundance of microsatellites in 14 fungal genomes.
AB  - An overview of the character of microsatellites in 14 fungal genomes was obtained
      by analyzing databases containing complete or nearly complete genome sequences.
      Low GC content, rather than genome size, was the best predictor of high
      microsatellite density, although very long iterations of tandem repeats were less
      common in small genomes. Motif type correlated with %GC in that low-GC genomes
      were more likely to be dominated by A/T-rich motifs, and vice versa, although
      some exceptions were noted. The experimentally useful dinucleotide and
      trinucleotide arrays were analyzed in greater detail. Although these varied in
      sequence and length among fungal species, some that are likely to be universally
      useful were identified. This information will be useful for researchers wanting
      to identify the most useful microsatellites to analyze for the fungi included in
      this survey and provides a platform for choosing microsatellites to target in
      fungi that are not yet sequenced.

PMID- 15465392
TI  - Arbuscular mycorrhizal fungi (Glomeromycota) harbour ancient fungal tubulin genes
      that resemble those of the chytrids (Chytridiomycota).
AB  - The genes encoding alpha- and beta-tubulins have been widely sampled in most
      major fungal phyla and they are useful tools for fungal phylogeny. Here, we
      report the first isolation of alpha-tubulin sequences from arbuscular mycorrhizal
      fungi (AMF). In parallel, AMF beta-tubulins were sampled and analysed to identify
      the presence of paralogs of this gene. The AMF alpha-tubulin amino acid phylogeny
      was congruent with the results previously reported for AMF beta-tubulins and
      showed that AMF tubulins group together at a basal position in the fungal clade
      and showed high sequence similarities with members of the Chytridiomycota. This
      is in contrast with phylogenies for other regions of the AMF genome. The amount
      and nature of substitutions are consistent with an ancient divergence of both
      orthologs and paralogs of AMF tubulins. At the amino acid level, however, AMF
      tubulins have hardly evolved from those of the chytrids. This is remarkable given
      that these two groups are ancient and the monophyletic Glomeromycota probably
      diverged from basal fungal ancestors at least 500 million years ago. The specific
      primers we designed for the AMF tubulins, together with the high molecular
      variation we found among the AMF species we analysed, make AMF tubulin sequences
      potentially useful for AMF identification purposes.

PMID- 15465393
TI  - A shift in nuclear state as the result of natural interspecific hybridization
      between two North American taxa of the basidiomycete complex Heterobasidion.
AB  - A natural first generation hybrid fungus shows interspecific heterozygosity. The
      nuclear condition of a rare natural hybrid between two taxa of the Heterobasidion
      complex is investigated. Heterobasidion species are known to be either
      homokaryotic (haploid) or heterokaryotic (n+n), but heterokaryons are made up of
      both homokaryotic and heterokaryotic sectors. The natural hybrid appears to be
      either a heterokaryon undergoing a primary homothallic phase or a diploid with
      limited ability to exchange nuclei when mated with homokaryons. The natural
      hybrid is stable and long lived, suggesting hybridization may play an important
      role in the evolutionary history of this fungal complex.

PMID- 15465394
TI  - Impact of Parkinson's disease on patients' adolescent and adult children.
AB  - We assessed the impact of Parkinson's disease (PD) on the well-being of patients'
      adolescent and adult children. Eighty-nine participants aged 12-48 completed a
      number of questionnaires on quality of life (QoL) and psychosocial variables. One
      fifth of the participants were mildly to moderately depressed, and children below
      the age of 18 years scored similarly to children with epilepsy in the domains of
      Attitude, School behaviour, and Social support on a QoL instrument for children
      with epilepsy. The impact of parental PD increased with disease duration. Younger
      children perceived a higher burden of daily help and impact on their social
      interactions than older children, while older participants reported greater
      impairment of family functioning. More than 50% felt that they did not have
      sufficient information about PD and half of all participants felt that more
      information would reduce their feelings of uncertainty and insecurity. PD has a
      marked effect on the well-being of the adult and adolescent children of patients.
      The difficulties of children of parents with PD should receive greater attention.

PMID- 15465395
TI  - Development of a measure of the impact of chronic parental illness on adolescent
      and adult children. The parental illness impact scale (Parkinson's disease).
AB  - Although chronic illness is likely to affect the well-being of patients'
      children, no assessment tools are currently available to measure this impact of
      parental illness. We therefore developed such an instrument based on interviews
      with children of patients with Parkinson's disease (PD). This questionnaire and
      other measures of psychological well-being were completed by 89 children, aged 12
      48, years of patients with PD. Factor analysis revealed six domains with 38
      questions. These six domains of the 'Parental Illness Impact Scale (Parkinson's
      disease)' or PIIS (PD) had satisfactory internal consistency and validity. Its
      six sub-scales correlated significantly and differentially with corresponding
      measures, including the Quality of Life in Epilepsy Inventory for Adolescents
      (QOLIE-AD-48; r = -0.2 to 0.85), the Beck Depression Inventory (r = -0.07 to 
      0.40) or Birleson Depression Self-Rating Scale (r = 0.04 to -0.62), and the
      Rosenberg Self-Esteem Scale (r = -0.01 to 0.33) as well as age (r = -0.37 to
      0.28) and parent's disease duration (r = -0.31 to 0.34). The PIIS is the first
      instrument to assess the impact of parental illness on children. Its psychometric
      properties should be tested further in larger samples, including children of
      patients with other chronic disorders such as multiple sclerosis or chronic heart
      disease.

PMID- 15465396
TI  - Smell testing is abnormal in 'lubag' or X-linked dystonia-parkinsonism: a pilot
      study.
AB  - We administered a culturally corrected University of Pennsylvania Smell
      Identification Test (ccUPSIT) consisting of 25 odor items to 20 patients with
      'Lubag' or X-linked dystonia-parkinsonism and 20 control subjects matched by sex,
      age, educational background, smoking history, and geographical origin. The mean
      ccUPSIT score of Lubag patients (18 +/- 3.19) was statistically lower (P = 0.003)
      than controls (20.5 +/- 3.02). The smell scores did not correlate with phenotype,
      severity of dystonia, or duration of disease. Nine of 20 Lubag patients (45%) had
      ccUPSIT scores below the mean, with the lowest score being 11. This pilot study
      suggests that olfactory dysfunction may occur in Lubag patients.

PMID- 15465397
TI  - Levodopa effect upon functional balance of Parkinson's disease patients.
AB  - OBJECTIVE: The aim of this study was to evaluate functional balance in PD
      patients taking levodopa during their 'on' and 'off' phases. DESIGN: We evaluated
      23 PD patients who were manifesting fluctuations of levodopa effect. All patients
      were assessed by Hoehn-Yahr, UPDRS-III and Schwab-England rating scales and by
      the Berg functional balance scale during a practically defined 'off' (at least
      after 12 h the last levodopa intake) and 'on' (the mobile state induced by the
      drug) phases. RESULTS: Mean scores obtained for all scales showed improvements
      during the 'on' phase of levodopa and all of the comparisons were statistically
      significant. Mean scores of Berg scale moved from 31.7 during the 'off' phase to
      42.7 during the 'on' phase. Mean UPDRS 'off' and 'on' scores were 50.6 and 32.0,
      respectively. CONCLUSION: We conclude that Berg functional balance scale is able
      to detect changes in balance and that levodopa can modify the postural
      instability of PD patients.

PMID- 15465398
TI  - Heart failure in Parkinson's disease: analysis of the United States medicare
      current beneficiary survey.
AB  - OBJECTIVE: We sought to examine the prevalence of heart failure in elderly PD
      versus non-PD patients using a national sample of Medicare beneficiaries in the
      United States. SCOPE: The prevalence of heart failure in elderly PD patients was
      2.27 times that of non-PD patients (19.4% versus 8.7%, 95% CI = 1.43-3.60, p
      0.0005), and remained twice as high after excluding patients with stroke and
      possible vascular parkinsonism. CONCLUSIONS: In this cross-sectional study of a
      national Medicare database, heart failure occurred twice as frequently in elderly
      PD patients as in non-PD patients. Prospective studies are warranted to verify
      these findings.

PMID- 15465399
TI  - DYT1 mutation in Korean primary dystonia patients.
AB  - One hundred sixty-two patients with Korean primary dystonia patients were
      screened for DYT1 mutation. Five patients were positive for DYT1 mutation.
      Generalized dystonia patients have higher rate of DYT1 mutation (3/7). Their
      onset age is young (7-20; mean 13.4). Two patients were found to have segmental
      dystonia. Like Japanese patients with DYT1 mutation, axial muscle involvement is
      notable.

PMID- 15465400
TI  - Levodopa-responsive parkinsonism in hereditary spastic paraplegia with thin
      corpus callosum.
AB  - Hereditary spastic paraplegia with thin corpus callosum is a rare degenerative
      disease, which is characterized by a progressive weakness of the lower limbs with
      a hypoplastic corpus callosum, and is often associated with other symptoms such
      as mental impairment, amyotrophy, sensory disturbances, dysuria, nystagmus and
      cataract. We describe two siblings (brother and sister) who showed a thin corpus
      callosum on MRI, one of whom showed the pure form of progressive spastic
      paraplegia, while the other showed predominant levodopa-responsive parkinsonism.
      The present cases are illustrative of a phenotypic heterogeneity in the same
      family of spastic paraplegia with a thin corpus callosum, despite the identical
      neuroimaging findings, and also presented another form of autosomal recessive
      juvenile levodopa-responsive parkinsonism.

PMID- 15465401
TI  - Unilateral periodic limb movement in sleep after supratentorial cerebral
      infarction.
AB  - We report a patient with involuntary right leg movements during sleep, which
      developed after acute ischemic stroke in the corona radiata. Nocturnal
      polysomnography confirmed the diagnosis of periodic limb movement in sleep
      (PLMS). Although the pathogenesis of PLMS is still controversial, it has been
      proposed that the loss of cortical or subcortical inhibition resulting from the
      pyramidal tract lesion might cause PLMS. The present case provides evidence to
      support this hypothesis.

PMID- 15465402
TI  - Validation and cross-cultural adjustment of PDQL-questionnaire, Spanish version
      (Ecuador) (PDQL-EV).
AB  - OBJECTIVE: To validate the Ecuadorian Spanish-language version of the Parkinson's
      Disease Quality of Life Questionnaire (PDQL-EV). METHOD: Cross-sectional study of
      patients with Parkinson's Disease attending a Movement Disorders Clinic. MEASURES
      APPLIED: Hoehn and Yahr (HY), Unified Parkinson's Disease Rating Scale (UPDRS
      3.0), Schwab and England Scale (SES), Pfeiffer Questionnaire (SPMSQ), Hospital
      Anxiety and Depression Scale (HADS). PDQ-39 and PDQL-EV were applied, the latter
      after translation and back translation. RESULTS: The study included 137 patients
      with an age range of 69.43 +/- 10.18 years (mean +/- SD), duration of illness
      5.87 +/- 2.58 years, and HY 2.28 +/- 0.77. The PDQL-EV internal consistency
      (Cronbach's alpha) yielded: Parkinson's symptoms (PS) 0.85; systemic symptoms
      (SS) 0.69; social function (SF) 0.81; and emotional function (EF) 0.78. The
      correlation between measurements varied from 0.68 (PS-SS) to 0.46 (SS-EF), and
      total measurement correlation from 0.58 (EF) to 0.74 (PS) (altogether, p <
      0.0001). The correlation of PDQL with clinical variables was: HY -0.62; UPDRS
      (subscales 1, 2 and 3) -0.55, -0.76, and -0.48, respectively; SES 0.65; SPMSQ 
      0.35; HADS-anxiety -0.55; HADS-depression -0.67; and PDQ-39 -0.91 (altogether p <
      0.0001). PDQL-EV scores were significantly different (p < 0.0001) between
      moderate and advanced stages, for all domains except for EF (p = 0.006).
      CONCLUSION: The PDQ-EV has satisfactory internal consistency, and converging and
      discriminating validity.

PMID- 15465403
TI  - Diabetes mellitus among parkinsonian patients treated chronically with clozapine.
AB  - Clozapine is the gold standard treatment for Parkinson's disease (PD) psychosis
      based on double blinded, placebo controlled trials, and has also been shown to
      alleviate tremor and dyskinesia. There is accumulating data suggesting that
      clozapine may be associated with increased frequency of diabetes mellitus (DM)
      compared to conventional neuroleptic drugs in treating schizophrenia. Forty-four
      predominantly geriatric parkinsonian subjects on clozapine for psychosis, tremor
      or dyskinesia, on an average dose of 50.6 mg/d for a mean duration of 41 months
      were reviewed. The prevalence of DM in this cohort was 18.1% (8/44). This rate
      was similar to that reported in the aged-matched general population (prevalence =
      19.3% for ages > or = 60 years). In this small study, parkinsonian patients on
      long-term, low dose clozapine were not at increased risk for developing DM.
      Larger controlled prospective studies are needed to confirm this.

PMID- 15465404
TI  - Superficial siderosis of the central nervous system associated with parkinsonism.

PMID- 15465406
TI  - Limb shaking transient ischemic attack--an unusual presentation of carotid
      occlusive disease. A case report and review of the literature.
AB  - Limb shaking transient ischemic attack (TIA) is an uncommon presentation of
      carotid occlusive disease. This unusual form of TIA is not well recognized and
      may be mistaken for focal epilepsy, delaying proper diagnosis and treatment. In
      this communication, we present such a case, together with a review of the
      literature, a brief account of pathophysiology and an outline of appropriate
      clinical management.

PMID- 15465405
TI  - Generalised myoclonus evolving into epilepsia partialis continua due to a
      cingulate gyrus lesion: case report and review of the literature.
AB  - A young Chinese male was admitted for a generalised tonic-clonic seizure preceded
      by a week-long history of fever. Subsequently, he developed continuous myoclonic
      jerks in all four limbs, with clear left sided predominance, and no accompanying
      clouding of consciousness. Contrast MRI of the brain demonstrated a venous
      angioma in the right cingulate gyrus. Over the next few days, the clinical
      picture evolved, with focal motor status involving primarily the left lower limb
      and the abdomen. These movements resolved with anticonvulsant therapy. This case
      illustrates generalised myoclonus arising from a focal brain abnormality. The
      epileptiform aetiology became obvious only after evolution into the typical
      features of a focal motor seizure and supportive neuroimaging. This demonstrates
      the protean manifestations of epileptic seizures which have been ascribed to the
      cingulate gyrus. The lack of clear declarative clinical and EEG features
      highlights the melding of the fields of epileptology and movement disorders.

PMID- 15465407
TI  - Effects of botulinum toxin-B (BTX-B) injections for hemifacial spasm.

PMID- 15465408
TI  - Laboratory investigations are indispensable to monitor the progress of measles
      elimination--results of the German Measles Sentinel 1999-2003.
AB  - BACKGROUND: The elimination of measles is a goal set by the World Health
      Organisation to be reached by 2010 in the European region. OBJECTIVES: To enhance
      the measles surveillance in Germany, a country-wide laboratory supported a
      sentinel was established. STUDY DESIGN: A network of >1200 representatively
      distributed practitioners reported detailed data on all clinically diagnosed
      cases and provided specimens for laboratory diagnosis. RESULTS: A total of 3225
      suspected cases were reported between October 1999 and December 2003. The
      incidence in Western Germany decreased from >15 cases per 100,000 population to
      one case in 2003, while in Eastern Germany <1 case per 100,000 population was
      observed during these years. Laboratory investigations were undertaken in 40% of
      cases in 2000/2001. This rate increased to 79% in 2003. Simultaneously, the rate
      of confirmed cases dropped from 60% in the former years to 23% in 2003. Measles
      virus (MV) detection by serology and by PCR revealed concordant results in 92%.
      Most suspected cases (85%) were unvaccinated with 66% being laboratory confirmed.
      Only 10% of suspected cases occurred in vaccinated individuals and very few (22%)
      could be confirmed. Analyses of confirmed measles in vaccinated patients (n = 49)
      revealed 24.5% primary vaccine failures, 24.5% reinfections after successful
      vaccination and 31% MV infection before or shortly after vaccination. The genetic
      characterisation of 389 MV isolates identified eight genotypes: B3, C2, D4, D5,
      D6, D7, G2 and H1. Only the C2, D6 and D7 MV genotypes circulated endemically in
      Western Germany. The newly emerged MV D7 almost completely replaced the pre
      existing C2 and D6 MVs in 2001. The few measles cases detected in Eastern Germany
      were mostly caused by imported MVs. CONCLUSION: The data demonstrate that
      laboratory investigations including molecular methods are an indispensable tool
      for surveillance in all countries advanced in measles elimination.

PMID- 15465409
TI  - Laboratory diagnosis of primary and secondary dengue infection.
AB  - BACKGROUND: Dengue fever is routinely detected in many laboratories using
      commercial tests for the specific detection of dengue IgM antibodies. OBJECTIVES:
      We have studied the sensitivity of IgM antibody detection in paired serum samples
      of 43 patients with either with primary dengue (PD) or secondary dengue (SD).
      STUDY DESIGN: Two consecutive samples were drawn from 23 Vietnamese and 20 German
      patients. All patients were selected for a positive PCR and for the fact that
      consecutive serum samples were available. The diagnosis of PD was based on
      seroconversion to dengue antigen and in SD on the detection of virus RNA in the
      presence of anti-dengue IgG antibodies. RESULTS: In samples of patients with PD
      fever taken during days 1-3 of the disease no IgM antibody could be detected.
      During days 4-7 and after day 7, IgM antibody was detected in 55% and 94%,
      respectively. In patients with SD fever, even less positive IgM samples were
      found in samples taken during days 4-7 (47%) and after day 7 (78%). IgG titers
      were significantly higher in SD compared to PD patients, although high (>1280)
      titers were also found in some PD patients. CONCLUSION: In numerous acute dengue
      fever patients an early diagnosis will be obtained only by combining IgM antibody
      detection with detection of virus or virus RNA using RT-PCR.

PMID- 15465410
TI  - Analysis of specific IgM responses in secondary dengue virus infections: levels
      and positive rates in comparison with primary infections.
AB  - BACKGROUND: Dengue viruses are a serious cause of illness in tropical and
      subtropical areas of the world. Laboratory diagnosis is essential for
      confirmation of dengue virus infections. Detection of specific IgM by IgM-capture
      enzymed-linked immunoassay (ELISA) has been widely used as a main serological
      diagnostic technique. OBJECTIVES: The levels of specific IgM in secondary dengue
      virus infections were compared with those in primary infections. STUDY DESIGN: A
      total of 1780 samples collected from 924 confirmed dengue cases were tested for
      anti-dengue IgM by IgM-capture ELISA. RESULTS AND CONCLUSIONS: Specific IgM was
      detected in all the cases with primary dengue virus infection on disease day 9 or
      later. However, specific IgM cannot be detected in 28% (204/716) of the cases in
      secondary infections. The average titers of IgM were higher in primary infections
      than in secondary infections. The results confirmed that IgM detection is a
      reliable serological diagnostic test in primary dengue virus infections. Although
      IgM detection is also a useful test, other serological diagnostic tests or tests
      for dengue virus detection are necessary for confirmation of all the secondary
      dengue virus infections.

PMID- 15465412
TI  - Effects of the G190A substitution of HIV reverse transcriptase on phenotypic
      susceptibility of patient isolates to delavirdine.
AB  - BACKGROUND: Cross resistance is common among the non-nucleoside reverse
      transcriptase inhibitors (NNRTIs). G190A appears in 5-15% of the patients treated
      with nevirapine or efavirenz who develop clinical resistance. OBJECTIVES: In this
      study we investigated the effect of G190A and other NNRTI substitutions on the
      phenotypic susceptibility to this class of drugs. STUDY DESIGN: We identified 15
      individuals, who after treatment with NNRTIs (nevirapine or efavirenz; median
      exposure of 20 months), developed isolated G190A, G190A in combination with
      K103N, or K103N alone. Phenotypic and genotypic analyses of stored plasma
      specimens were performed before and after the mutations occurred to assess NNRTI
      susceptibility. RESULTS: All isolates that developed only G190A substitution
      became less susceptible to nevirapine (median: 125-fold) and efavirenz (median:
      10-fold) but were 2.5-fold more sensitive to delavirdine (Wilcoxon P = 0.06). In
      the group with only K103N substitution, acquisition of resistance to all NNRTIs
      was observed. In the group with the double substitutions, G190A and K103N,
      delavirdine susceptibility decreased 13-fold, while resistance to nevirapine and
      efavirenz decreased by 239- and 154-folds, respectively (Kruskal-Wallis H P =
      0.009). CONCLUSIONS: The data suggest that the presence of a G190A substitution
      attenuates the phenotypic resistance associated with a K103N substitution,
      although resistance is still present. The in vivo significance of the increased
      phenotypic susceptibility to delavirdine is not known but could be evaluated in a
      clinical trial.

PMID- 15465411
TI  - Amniotic fluid has higher relative levels of lentivirus-specific antibodies than
      plasma and can contain neutralizing antibodies.
AB  - BACKGROUND: The in utero transmission rate of HIV-1 is estimated to be 10-15% in
      the absence of interventions and breastfeeding. Natural protective mechanisms
      involving lentivirus-specific antibodies may therefore exist to limit in utero
      transmission of lentiviruses. OBJECTIVES: HIV-1- and SIV-specific immunoglobulin
      G (IgG) levels in amniotic fluid samples from humans and rhesus macaques were
      assessed. STUDY DESIGN: HIV-1- and SIV-specific immunoglobulin G levels, relative
      to total IgG concentrations in amniotic fluid samples from humans and rhesus
      macaques, were determined using a quantitative Western blotting procedure.
      Amniotic fluid from rhesus macaques was tested for the ability to neutralize SIV
      infection of CEMX174 cells. RESULTS: The levels of HIV-1- and SIV-specific
      immunoglobulin G, relative to total IgG concentrations in amniotic fluid samples
      from humans and rhesus macaques, were approximately 3-10-fold higher than in
      plasma. The ability of antibodies in human amniotic fluid samples to neutralize
      viral infectivity could not be assessed, because zidovidine was present in the
      samples. Most amniotic fluid samples from rhesus macques not treated with
      antiretrovirals were able to neutralize SIV infectivity, except for a sample from
      a SIV positive rhesus whose infant was infected in utero. CONCLUSIONS: Active
      immunity to HIV-1 resulting in virus-specific antibodies in amniotic fluid
      exists, and may be a natural barrier to in utero infection. This may provide hope
      for stimulating neutralizing antibody via vaccine design.

PMID- 15465413
TI  - HPV DNA in plasma of patients with cervical carcinoma.
AB  - BACKGROUND: HPV DNA has been detected in metastatic tumour and HPV plasma
      viraemia may indicate a poor prognosis and a high risk for metastasis. OBJECTIVE:
      Detection of HPV DNA in plasma of patients with cervical carcinoma. STUDY DESIGN:
      A cross-sectional study was done, wherein cervical biopsies and plasma samples
      were collected from 58 women with invasive cervical carcinoma, 10 women with
      cervical intraepithelial neoplasia (CIN) and 30 control women in the same age
      range. Polymerase chain reaction (PCR) was employed to detect the presence of HPV
      DNA. Samples positive for HPV DNA were typed by restriction fragment length
      polymorphism (RFLP). To confirm that the HPV sequence in plasma was identical to
      that in tissue, sequencing was done on all the paired plasma and tissue samples.
      RESULTS: All the 30 paired cervical tissue and plasma samples from the controls
      were negative for HPV DNA. HPV DNA was detectable in cervical tissues of 55
      (94.8%) of 58 patients with invasive cervical carcinoma and in all 10 patients
      (100%) with CIN and in eight (11.8%) of the total 68 plasma samples from
      patients. All eight plasma samples were from women with invasive cervical
      carcinoma with three each in stages IIIB and IV and one each in stages IIB and
      IB, respectively. Of the eight positive samples, seven were typed as HPV-16 and 1
      as HPV-58. HPV types detected in cervical tissue and plasma pairs from these
      eight patients correlated as revealed by RFLP and sequencing. A patient with
      stage IB cancer had detectable HPV DNA in the external iliac lymph node, removed
      at Wertheims hysterectomy, which was histopathologically free of tumour. The HPV
      type in the node, was the same as that present in the paired tissue and plasma
      sample. CONCLUSIONS: HPV DNA is detectable in the plasma of patients with
      advanced cervical cancer.

PMID- 15465414
TI  - Prevalence of cryoglobulinemia in hepatitis C virus (HCV) positive patients with
      and without human immunodeficiency virus (HIV) coinfection.
AB  - BACKGROUND: Coinfection with human immunodeficiency virus (HIV) has been shown to
      influence the natural history of hepatitis C infection. OBJECTIVE: Our interest
      was to determine if HIV coinfection influences the prevalence of cryoglobulinemia
      in hepatitis C virus (HCV) infected persons. STUDY DESIGN: A total of 384 HCV RNA
      positive (234 HIV-infected and 150 HIV-uninfected) participants were tested at
      two visits, 18 months apart, for HCV and HIV RNA, CD4, and liver enzyme levels.
      Serum cryoglobulin levels were measured at a subsequent visit for a subset of the
      sample. RESULTS: HIV-infected participants had significantly higher HCV RNA
      levels (P < 0.0001) and aspartate transaminase (AST) levels (P < 0.0001), but not
      alanine transaminase (ALT) levels (P > 0.05) as compared with HIV-uninfected
      participants. These findings were consistent at both visits and no significant
      changes were observed between visits. Fifty (19%) of the 264 participants tested
      had detectable cryoglobulins. No difference was observed in HIV seropositivity
      among participants with or without cryoglobulinemia (68% versus 61%; odds ratio =
      1.34, P = 0.37). However, among HIV coinfected participants, elevated AST levels
      (P = 0.04) and lower CD4 levels (P = 0.02) were associated with cryoglobulinemia.
      CONCLUSIONS: While previously reported associations were found between HIV and
      coinfection with HCV in this study, we did not find an association between HIV
      infection and cryoglobulinemia.

PMID- 15465415
TI  - Impact of frequent natural polymorphisms at the protease gene on the in vitro
      susceptibility to protease inhibitors in HIV-1 non-B subtypes.
AB  - BACKGROUND: Naturally-occurring polymorphisms at the human immunodeficiency virus
      type 1 (HIV-1) protease which have been associated to resistance to protease
      inhibitors (PIs) in clade B viruses are frequently found in non-B subtypes, with
      unknown clinical significance. OBJECTIVE: To assess the susceptibility of non-B
      viruses to different PIs. STUDY DESIGN: Plasma samples from 58 drug-naive
      individuals infected with HIV-1 non-B subtypes (2A, 22C, 2D, 1F, 29G and 2J)
      defined by phylogenetic analyses of the protease gene were tested using a
      phenotypic assay (PhenoSense, ViroLogic, South San Francisco, CA, USA). Twenty of
      them were further analyzed with another assay (Antivirogram, Virco, Mechelen,
      Belgium). All 58 non-B viruses harbored amino acid substitutions associated with
      reduced PI susceptibility in clade B (positions 10, 20, 36, 63, 70, 77 and 82).
      RESULTS: Using PhenoSense-HIV assay, all but two individuals harbored viruses
      completely susceptible to all six PIs tested (indinavir (IDV), ritonavir (RTV),
      saquinavir (SQV), nelfinavir (NFV), amprenavir (APV), lopinavir (LPV)). The two
      viruses with reduced susceptibility belonged to clade G. The first virus, which
      had K20I, M36I and V82I, showed 2.9-fold decreased susceptibility to APV, while
      the second virus showed 3.9-fold decreased susceptibility to both NFV and RTV,
      with amino acid substitutions K20I, M36I, L63P and V82I. Of note, several other
      viruses displayed the same constellation of mutations but without showing any
      reduced susceptibility, suggesting that these polymorphisms per se do not affect
      PI susceptibility. CONCLUSION: PI susceptibility in HIV-1 non-B viruses seems to
      be preserved despite the presence of polymorphic changes which have been
      associated to PI resistance in clade B viruses.

PMID- 15465416
TI  - HIV-1 infection among injection and ex-injection drug users from Rio de Janeiro,
      Brazil: prevalence, estimated incidence and genetic diversity.
AB  - BACKGROUND AND OBJECTIVES: Due to their behavioral conditions and vulnerability,
      injection drug users (IDUs) are prone to multiple simultaneous or sequential
      infections with distinct HIV-1 subtypes and variants, making them a key
      population for molecular epidemiology surveillance. In the present study, we
      evaluated HIV-1 infection seroprevalence, genetic diversity and estimated
      incidence among IDUs and ex-injection drug users (ex-IDUs) from Rio de Janeiro,
      Brazil. STUDY DESIGN: Six hundred and eight IDUs and ex-IDUs, recruited between
      1999 and 2001, were interviewed and agreed to donate 30 ml of blood. The
      serologic status for HIV infection was determined by two ELISAs and confirmed by
      IFA. CD4+ T-cell percentages were assessed by flow cytometry. HIV-1 positive
      samples were submitted to viral load quantification. DNA samples were PCR
      amplified and HIV-1 subtypes were determined using env and gag HMA. RESULTS AND
      CONCLUSIONS: Forty-eight (7.89%) individuals were seropositive for HIV-1
      infection. The seroincidence of HIV-1 infection was estimated as 0.76%. HIV-1 env
      and gag subtyping identified 29 (69%) samples as belonging to subtype B, 7
      (16.7%) to subtype F, and 6 (14.3%) discordant env/gag genomes infections,
      indicating the circulation of recombinant viruses in this population.

PMID- 15465417
TI  - TaqMan amplification system with an internal positive control for HCV RNA
      quantitation.
AB  - BACKGROUND: Quantitation of hepatitis C virus (HCV) RNA has become an essential
      tool for monitoring antiviral therapies in chronically infected patients.
      Different quantitative HCV RNA assays have been reported, mainly using techniques
      based on signal amplification with branched DNA (bDNA) technology or target
      sequence amplification by reverse-transcription PCR method (RT-PCR). OBJECTIVES
      AND STUDY DESIGN: An RT-PCR assay using TaqMan (fluorescence-based real-time PCR)
      and minor groove binding (MGB) probes was designed for the quantitative
      determination of HCV RNA in the clinical samples. Calculation of the
      concentration of HCV RNA was based on an external standard curve in the presence
      of an internal positive control (IPC). RESULTS: The assay detected 550
      international units (IU)/mL with >95% probability of a positive result, with a
      linear range extending up to 10,000,000 IU/mL. The test exhibited good
      reproducibility with intra-assay and inter-assay coefficients of variation (CV)
      of 1.6% and 3.2%, respectively. All the major HCV genotypes were quantified with
      equivalent efficiency and accuracy. HCV genotypes 5 and 6 have also been
      amplified but too few samples have been tested. The performance of this new assay
      for quantitation of HCV viremia was evaluated with 213 anti-HCV positive sera,
      120 of which corresponded to 30 patients sampled during the therapy. We used the
      Amplicor HCV Monitor assay (Roche Diagnostics, France) and the bDNA VERSANT HCV
      RNA assay (Bayer Diagnostics, France) to analyze 173 and 40 samples,
      respectively. The assay described here was significantly correlated with both
      commercial assays (R2 = 0.9535, P < 0.0001 and R2 = 0.8508, P < 0.0001,
      respectively). CONCLUSION: The present study illustrated the high reproducibility
      and reliability of our TaqMan HCV assay. Moreover, the monitoring of viral
      decline with our assay gave the same results as those obtained with the
      commercial assays indicating that this new technique provides an attractive
      approach for measuring HCV viral load.

PMID- 15465418
TI  - Virological and immunological characteristics of a 19-year-old Japanese female
      with fatal outcome with Epstein-Barr virus-associated hemophagocytic syndrome.
AB  - Hemophagocytic syndrome (HPS) is caused by the hyperactivation of T-cells and
      macrophages. The clinical characteristics associated with this disease result
      from overproduction of cytokines including interferon-gamma (INF-gamma), tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6). HPS presents with fever,
      liver dysfunction, coagulation abnormalities, pancytopenia, and a benign
      histiocytic proliferation with prominent hemophagocytosis in bone marrow, lymph
      node, spleen, and liver. We describe a 19-year-old female with fatal HPS. She had
      been given corticosteroid every other day for systemic lupus erythematosus (SLE)
      without flare up. The causative underlying disease was acute primary Epstein-Barr
      virus (EBV) infection. EBV genomes were detected by the polymerase chain reaction
      (PCR). To measure the virus load we use a real-time PCR assay to quantify the
      amount of EBV DNA in peripheral blood lymphocytes, lung, kidney, brain and liver
      at autopsy. Further in situ hybridisation (ISH) and immunohistochemical studies
      demonstrated that Epstein-Barr virus encoded small RNA (EBER) was detected in
      CD8+ T-cells in bone marrow, lung, kidney, brain, liver and spleen. In each
      organ, mRNA levels of inflammatory cytokines (INF-gamma, TNF-alpha, IL-6) were
      highly detected compared with beta-Actin mRNA levels. These results suggest that
      EBV-infected CD8+ T-cells in each organ (peripheral blood lymphocytes, lung,
      kidney, brain and liver) may have an integral role in the pathophysiology of the
      HPS.

PMID- 15465420
TI  - Niemann-Pick C research from mouse to gene.
AB  - Understanding the molecular basis of Niemann-Pick C (NP-C) disease took decades
      of struggle. Here I describe our early efforts to unravel the complex lipid
      storage found in NP-C tissues, and how the mouse model for NP-C pointed us in the
      right direction. Our success in cloning the NP-C1 gene in 1997 can be attributed
      to collaboration between an international body of scientists and families coping
      with NP-C disease. The next challenge is to delineate the biological function of
      the NP-C1 protein.

PMID- 15465421
TI  - The NPC1 protein: structure implies function.
AB  - Niemann-Pick type C (NPC) is a lysosomal storage disorder, characterized by
      intracellular accumulation of low-density lipoprotein (LDL)-derived cholesterol
      and neurodegeneration leading to premature death. The most common form of the
      disease, NPC1, results from mutations in the NPC1 gene. Thus, the NPC1 protein is
      the focus of intense investigation to elucidate the function of this protein and
      its role in the disease pathogenesis. Recent studies have revealed the NPC1
      subcellular location, topology and potential functions of the NPC1 protein. In
      lieu of direct experimental evidence, certain hypotheses about the function of
      NPC1 can be inferred by analyzing disease-causing mutations, NPC1 protein
      sequence homology to other related proteins, and the potential tertiary structure
      similarity between NPC1 and its prokaryotic ancestors, such as the E. coli RND
      permease AcrB. This review will discuss recent work on the characterization and
      function of the NPC1 protein and highlight structural features that may be
      important in assisting in the elucidation of NPC1 function and role in
      subcellular lipid transport and homeostasis.

PMID- 15465422
TI  - Structure and function of the NPC2 protein.
AB  - Somatic cell hydridization and linkage studies indicated the implication of a
      second gene as a cause of Niemann-Pick C disease in a minority (5%) of patients.
      A study of the lysosomal proteome led to the identification of a previously known
      gene, HE1, as the NPC2 gene. The mature NPC2/HE1 protein is a ubiquitous soluble
      small 132-amino-acid glycoprotein, first characterized as a major secretory
      protein in the human epididymis, but also detected in most tissues. Seventeen
      families with mutations in the NPC2 gene are known. Good genotype-phenotype
      correlations were observed. No distinction can be made between the biochemical
      phenotypes of NPC1 or NPC2 mutants. The NPC2 protein binds cholesterol with
      submicromolar affinity at neutral and acidic pH. The bovine protein has been
      crystallized, and the cholesterol-binding site assigned to a hydrophobic loosely
      packed region. There is strong evidence that the NPC1 and NPC2 proteins must
      function in a closely related fashion. Current data have led to the hypothesis
      that NPC2 would bind cholesterol from internal lysosomal membranes, enabling a
      physical interaction with NPC1 (or another protein) and allowing postlysosomal
      export of cholesterol. In this model, the activity of NPC1 would depend on that
      of NPC2. The precise function of the NPC2 protein has, however, not been fully
      elucidated.

PMID- 15465423
TI  - Intracellular trafficking of Niemann-Pick C proteins 1 and 2: obligate components
      of subcellular lipid transport.
AB  - Niemann-Pick C 1 (NPC1) is a large integral membrane glycoprotein that resides in
      late endosomes, whereas NPC2 is a small soluble protein found in the lumen of
      lysosomes. Mutations in either NPC1 or NPC2 result in aberrant lipid transport
      from endocytic compartments, which results in lysosomal storage of a complex
      mixture of lipids, primarily cholesterol and glycosphingolipids. What are the
      biological functions of the NPC1 and NPC2 proteins? Here we review what is known
      about the intracellular itinerary of these two proteins as they facilitate lipid
      transport. We propose that the intracellular trafficking patterns of these
      proteins will provide clues about their function.

PMID- 15465424
TI  - Lipid and cholesterol trafficking in NPC.
AB  - Niemann-Pick type C, or NPC for short, is an early childhood disease exhibiting
      progressive neurological degeneration, associated with hepatosplenomegaly in some
      cases. The disease, at the cellular level, is a result of improper trafficking of
      lipids such as cholesterol and glycosphingolipids (GSLs) to lysosome-like storage
      organelles (LSOs), which become engorged with these lipids. It is believed that
      the initial defect in trafficking, whether of cholesterol or a GSL, results in an
      eventual traffic jam in these LSOs. This leads to the retention of not only other
      lipids, but also of transmembrane proteins that transiently associate with the
      late endosomes (LE) in normal cells, on their way to other cellular destinations
      such as the trans-Golgi network (TGN). In this review, we discuss the biophysical
      properties of lipids and cholesterol that might determine their intracellular
      itineraries, and how these itineraries are altered in NPC cells, which have
      defects in the proteins NPC1 or NPC2. We also discuss some potential therapeutic
      directions being suggested by recent research.

PMID- 15465425
TI  - Metazoan and microbial models of Niemann-Pick Type C disease.
AB  - Niemann-Pick Type C (NP-C) disease compellingly provides insight into lipid
      transport and the association of this process with severe neuronal dysfunction.
      The two genes that define this syndrome, NPC1 and NPC2, are conserved throughout
      much of eukaryotic evolution, to the extent that the yeast and mammalian NPC1
      genes are functionally interchangeable. We present here an evolutionary
      perspective of the genes defective in NP-C disease. We will describe how
      conservation of sequences and their biological roles in a variety of microbial
      and metazoan model systems may act as roadmaps to understanding this syndrome in
      humans.

PMID- 15465426
TI  - Consequences of NPC1 and NPC2 loss of function in mammalian neurons.
AB  - Genetic deficiency of NPC1 or NPC2 results in a devastating cholesterol
      glycosphingolipidosis of brain and other organs known as Niemann-Pick type C
      (NPC) disease. While NPC1 is a transmembrane protein believed involved in
      retroendocytic shuttling of substrate(s) to the Golgi and possibly elsewhere in
      cells as part of an essential recycling/homeostatic control mechanism, NPC2 is a
      soluble lysosomal protein known to bind cholesterol. The precise role(s) of NPC1
      and NPC2 in endosomal-lysosomal function remain unclear, nor is it known whether
      the two proteins directly interact as part of this function. The pathologic
      features of NPC disease, however, are well documented. Brain cells undergo
      massive intracellular accumulation of glycosphingolipids (lactosylceramide,
      glucosylceramide, GM2 and GM3 gangliosides) and cholesterol and concomitant
      distortion of neuron shape (meganeurite formation). In neurons from humans with
      NPC disease the metabolic defects and storage often lead to extensive growth of
      new, ectopic dendrites (possibly linked to ganglioside sequestration) as well as
      formation of neurofibrillary tangles (NFTs) (possibly linked to dysregulation of
      cholesterol metabolism). Other features of cellular pathology in NPC disease
      include fragmentation of the Golgi apparatus and neuroaxonal dystrophy, though
      reasons for these changes remain largely unknown. As the disease progresses,
      neurodegeneration is also apparent for neurons in some brain regions,
      particularly Purkinje cells of the cerebellum, but the basis of this selective
      neuronal vulnerability is unknown. The NPC1 protein is evolutionarily conserved
      with homologues reported in yeast to humans; NPC2 is reported in C. elegans to
      humans. While neurons in mammalian models of NPC1 and NPC2 diseases exhibit many
      changes that are remarkably similar to those in humans (e.g., endosomal/lysosomal
      storage, Golgi fragmentation, neuroaxonal dystrophy, neurodegeneration), a
      reduced degree of ectopic dendritogenesis and an absence of NFTs in these species
      suggest important differences in the way lower mammalian neurons respond to
      NPC1/NPC2 loss of function.

PMID- 15465427
TI  - Before the loss: neuronal dysfunction in Niemann-Pick Type C disease.
AB  - Niemann-Pick Type C (NPC) disease is an autosomal recessive disorder caused by
      mutations in either the NPC1 or HE1 genes. Hallmarks of this presently incurable
      disease include abnormal intracellular accumulation of cholesterol and
      glycosphingolipids, progressive neuropathology and neurodegeneration, and
      premature death. There have been increased efforts to understand the effects of
      NPC disease on neurons of the brain, in part due to the recent development of
      improved research tools and reagents, and in part due to the rapidly growing
      appreciation of the importance of cholesterol and lipoproteins in the brain
      during neuronal development, function, and degeneration. Here, we highlight
      fundamental aspects of neurons that appear to be affected by NPC disease,
      including their morphology, metabolism, intracellular transport, electrical
      signaling, and response to environmental factors, and suggest other potentially
      important areas for future investigation. This provides a framework for acquiring
      additional insight to this disorder and shaping new therapeutic approaches to NPC
      disease.

PMID- 15465428
TI  - Therapy of Niemann-Pick disease, type C.
AB  - Niemann-Pick disease, type C (NPC) is a progressive autosomal recessive
      neurodegenerative disease, characterized by late endosomal-lysosomal accumulation
      of multiple lipid molecules in association with abnormal tubulovesicular
      trafficking. The major gene product, NPC1 protein, is not suitable for
      transduction therapies, and gene replacement or repair is not yet practicable for
      NPC and related disorders. Attempts at therapy to date have focused on reduction
      of the accumulating molecules that are presumed to have direct or indirect toxic
      effects. More recent insights into the pathophysiology of NPC raise the
      possibility of small molecule therapies to interdict pathways triggering
      apoptosis and related routes to cell death and dysfunction.

PMID- 15465429
TI  - The pathophysiology and mechanisms of NP-C disease.
AB  - The molecular isolation of NPC1 and NPC2, the genes defective in patients with
      Niemann-Pick disease type C (NP-C), has heralded in an exponential increase in
      our understanding of this syndrome and thus of human intracellular sterol
      transport. Despite this, neither the mechanisms of action nor the substrates for
      these putative transporters have been defined. In this overview, we describe our
      perspectives on the current awareness of the genetic determination and cellular
      biology of this syndrome, with emphasis on the underlying events that lead to
      neurodegeneration and the manner in which they might eventually be treated.

PMID- 15465430
TI  - Selection of stimulus parameters for deep brain stimulation.
AB  - OBJECTIVE: To provide an analysis of stimulation parameters for deep brain
      stimulation (DBS). METHODS: Synthesis of theoretical and empirical findings is
      used to provide guidance for the selection of stimulus parameters. Finite element
      modeling is used to investigate the effects of contact location and electrode
      geometry on the electric field, and to estimate the effects of current density
      distribution on the limit for non-damaging stimulation. RESULTS: Anatomical
      targeting of DBS electrodes is complicated by the uncertainty of which neural
      elements are targeted and differences in the electric field distribution in fiber
      tracts and nuclei. Electrical targeting by selection of electrode geometry and
      stimulus waveform can alter the distribution of the electric field and control
      neural activation. The recommended charge density limit for DBS represents a
      liberal estimate for non-damaging stimulation. Short duration stimulus pulses
      reduce charge injection and increase the therapeutic window between therapeutic
      effects and side effects. CONCLUSIONS: There are several challenges to developing
      rational methods of selecting stimulus parameters including a large number of
      degrees of freedom, the unknown effects of stimulation, and the complexity of the
      responses. SIGNIFICANCE: Understanding the fundamentals of electrical stimulation
      of the nervous system enables rational selection of stimulus parameters.

PMID- 15465431
TI  - Heart rate activation during spontaneous arousals from sleep: effect of sleep
      deprivation.
AB  - OBJECTIVE: Arousal (AR) from sleep is associated with an autonomic reflex
      activation raising blood pressure and heart rate (HR). Recent studies indicate
      that sleep deprivation may affect the autonomic system, contributing to high
      vascular risk. Since in sleep disorders a sleep fragmentation and a partial sleep
      deprivation occurs, it could be suggested that the cardiovascular effects
      observed at AR from sleep might be physiologically affected when associated with
      sleep deprivation. The aim of the study was to examine the effect of sleep
      deprivation on cardiac arousal response in healthy subjects. METHODS: Seven
      healthy male subjects participated in a 64 h sleep deprivation protocol. Arousals
      were classified into four groups, i.e. >3<6 s, >6<10 s, >10<15 s and >15 s,
      according to their duration. Pre-AR HR values were measured during 10 beats
      preceding the AR onset, and the event-related HR fluctuations were calculated
      during the 20 beats following AR onset. As an index of cardiac activation, the
      ratio of highest HR in the post-AR period over the lowest recorded before AR (HR
      ratio) was calculated. RESULTS: For AR lasting less than 10 s, the occurrence of
      AR induces typical HR oscillations in a bimodal pattern, tachycardia followed by
      bradycardia. For AR lasting more than 10 s, i.e. awakenings, the pattern was
      unimodal with a more marked and sustained HR rise. The HR response was
      consistently similar across nights, during NREM and REM sleep, without difference
      between conditions. CONCLUSIONS: Overall, total sleep deprivation appeared to
      have no substantial effect on cardiac response to spontaneous arousals and
      awakenings from sleep in healthy subjects. Further studies are needed to clarify
      the role of chronic sleep deprivation on cardiovascular risk in patients with
      sleep disorders. SIGNIFICANCE: In healthy subjects acute prolonged sleep
      deprivation does not affect the cardiac response to arousal.

PMID- 15465432
TI  - The effects of neurofeedback training on the spectral topography of the
      electroencephalogram.
AB  - OBJECTIVE: To investigate the impact of EEG frequency band biofeedback
      (neurofeedback) training on spectral EEG topography, which is presumed to mediate
      cognitive-behavioural training effects. In order to assess the effect of commonly
      applied neurofeedback protocols on spectral EEG composition, two studies
      involving healthy participants were carried out. METHODS: In Experiment 1,
      subjects were trained on low beta (12-15 Hz), beta1 (15-18 Hz), and alpha/theta
      (8-11 Hz/5-8 Hz) protocols, with spectral resting EEG assessed before and after
      training. The specific associations between learning indices of each individual
      training protocol and changes in absolute and relative spectral EEG topography
      was assessed by means of partial correlation analyses. Results of Experiment 1
      served to generate hypotheses for Experiment 2, where subjects were randomly
      allocated to independent groups of low beta, beta1, and alpha/theta training.
      Spectral resting EEG measures were contrasted prior and subsequent to training
      within each group. RESULTS: Only few associations between particular protocols
      and spectral EEG changes were found to be consistent across the two studies, and
      these did not correspond to expectations based on the operant contingencies
      trained. Low-beta training was found to be somewhat associated with reduced post
      training low-beta activity, while more reliably, alpha/theta training was
      associated with reduced relative frontal beta band activity. CONCLUSIONS: The
      results document that neurofeedback training of frequency components does affect
      spectral EEG topography in healthy subjects, but that these effects do not
      necessarily correspond to either the frequencies or the scalp locations addressed
      by the training contingencies. The association between alpha/theta training and
      replicable reductions in frontal beta activity constitutes novel empirical
      neurophysiological evidence supporting inter alia the training's purported role
      in reducing agitation and anxiety. SIGNIFICANCE: These results underline the
      complexity of the neural dynamics involved EEG self-regulation and emphasize the
      need for empirical validation of predictable neurophysiological outcomes of
      training EEG biofeedback protocols.

PMID- 15465434
TI  - Serial EEG findings in sporadic and iatrogenic Creutzfeldt-Jakob disease.
AB  - OBJECTIVE: To study temporal and spatial development of EEG patterns in sporadic
      and iatrogenic Creutzfeldt-Jakob disease patients. METHODS: Temporal and spatial
      development of EEG patterns in 4 patients with sporadic Creutzfeldt-Jakob disease
      and 2 patients with iatrogenic Creutzfeldt-Jakob disease due to implantation of
      contaminated brain depth electrodes were investigated. A total of 56 EEGs were
      analyzed, over time spans ranging from 1272 to 3 days prior to death. RESULTS:
      Frontal intermittent rhythmical delta activity (FIRDA) was seen at early
      timepoints in 4/6 patients and might represent an early EEG pattern that is
      associated, with human prion diseases. EEG patterns associated with CJD are
      sensitive to midazolam. Initial EEG changes were seen at the site of prion
      exposure in iatrogenic Creutzfeldt-Jakob disease patients, before they could be
      observed at distant sites, suggesting that prion disease was initiated at the
      site of prion exposure. CONCLUSIONS: Serial EEG recordings are a valuable tool
      not only in the early diagnosis of sporadic CJD, but also in the determination of
      prion exposure in iatrogenic Creutzfeldt-Jakob disease. SIGNIFICANCE: FIRDA occur
      at an early stage of CJD and are progressively replaced by the classical PSWC.
      The EEG patterns of CJD are sensitive to midazolam. The initial EEG changes in
      iatrogenic CJD are seen at the site of prion exposure.

PMID- 15465433
TI  - Spectral analysis of burst periods in EEG from healthy and post-asphyctic full
      term neonates.
AB  - OBJECTIVE: To investigate whether the periodic EEG patterns seen in healthy and
      sick full term neonates (trace alternant and burst suppression, respectively)
      have different frequency characteristics. METHODS: Burst episodes were selected
      from the EEGs of 9 healthy and 9 post-asphyctic full-term neonates and subjected
      to power spectrum analysis. Powers in two bands were estimated; 0-4 and 4-30 Hz,
      designated low- and high-frequency activity, respectively (LFA, HFA). The
      spectral edge frequency (SEF) was also assessed. RESULTS: In bursts, the LFA
      power was lower in periods of burst suppression as compared to those of trace
      alternant. The parameter that best discriminated between the groups was the
      relative amount of low- and high-frequency activity. The SEF parameter had a low
      sensitivity to the group differences. In healthy neonates, the LFA power was
      higher over the posterior right as compared to the posterior left region.
      CONCLUSIONS: Spectral power of low frequencies differs significantly between the
      burst episodes of healthy and sick neonates. SIGNIFICANCE: These results can be
      used when monitoring cerebral function in neonates.

PMID- 15465435
TI  - Positive temporal sharp waves in preterm infants with and without brain
      ultrasound lesions.
AB  - OBJECTIVE: Clinical significance of neonatal positive temporal sharp waves (PTS)
      is controversial. The aim of this work is to study (1) PTS incidence in preterm
      infants with or without major ultrasound lesion (MUL) per gestational age (GA),
      and (2) the relationship between PTS in both sleep states and other
      electroencephalographic (EEG) findings with poor prognoses. METHODS: 97 preterm
      infants of <27-36 weeks GA, and 12 full-term healthy infants were presented.
      Prospective study included (1) neurodevelopmental assessment at 40-42 weeks
      conceptional age (CA), (2) serial neurosonography, and (3) EEG recording at
      postnatal week 1, 2, 4 and at 40-42 weeks CA. RESULTS: In 50 neonates without
      MUL, peak PTS was at 31-32 weeks GA. In 47 neonates with MUL, PTS increased
      significantly from week 2 after birth, descending at the 4th. Neonates of <33
      weeks GA with MUL showed significantly increased PTS at term. A significant
      relationship was found between PTS and other EEG abnormalities with poor
      neurologic prognoses. PTS incidence varied with sleep states, being predominant
      in indeterminate sleep in neonates with MUL. CONCLUSIONS: PTS increased
      significantly in infants with MUL, mainly at week 2 of postnatal life, persisting
      high until term CA, and correlated with other abnormal EEG findings.
      SIGNIFICANCE: PTS are highly sensitive to MUL.

PMID- 15465436
TI  - Night terrors associated with thalamic lesion.
AB  - OBJECTIVE: To describe a case with night terrors (NT) symptomatic of a thalamic
      lesion. METHODS: Videopolysomnography and brain MRI were used to study a 48 year
      old woman with a recent onset of brief episodes, occurring exclusively during
      nocturnal sleep, where she suddenly sat up in bed, screamed and appeared to be
      very frightened. RESULTS: Videopolysomnography recorded an episode suggestive of
      NT. Sleep fragmentation with frequent brief arousals or microarousals was also
      evident mainly during slow wave sleep. The brain MRI showed increased T2 signal
      from the right thalamus suggestive of a low-grade tumor. CONCLUSIONS: Our case
      suggests that NT starting in adulthood can, rarely, be symptomatic of
      neurological disease, and warrant further investigation with MRI. SIGNIFICANCE: A
      thalamic dysfunction, disrupting at this level the arousal system, may play a
      role in provoking NT.

PMID- 15465437
TI  - Quantification of Uhthoff's phenomenon in multiple sclerosis: a magnetic
      stimulation study.
AB  - OBJECTIVE: To quantify temperature induced changes (=Uhthoff phenomenon) in
      central motor conduction and their relation to clinical motor deficits in 20
      multiple sclerosis (MS) patients. METHODS: Self-assessment of vulnerability to
      temperature and clinical examination were performed. We used motor evoked
      potentials to measure central motor conduction time (CMCT) and applied the triple
      stimulation technique (TST) to assess conduction failure. The TST allows an
      accurate quantification of the proportion of conducting central motor neurons,
      expressed by the TST amplitude ratio (TST-AR). RESULTS: Temperature induced
      changes of TST-AR were significantly more marked in patients with prolonged CMCT
      (P=0.037). There was a significant linear correlation between changes of TST-AR
      and walking velocity (P=0.0002). Relationships were found between pronounced
      subjective vulnerability to temperature and (i) abnormal CMCT (P=0.02), (ii)
      temperature induced changes in TST-AR (P=0.04) and (iii) temperature induced
      changes in walking velocity (P=0.04). CMCT remained virtually unchanged by
      temperature modification. CONCLUSIONS: Uhthoff phenomena in the motor system are
      due to varying degrees of conduction block and associated with prolonged CMCT. In
      contrast to conduction block, CMCT is not importantly affected by temperature.
      SIGNIFICANCE: This is the first study quantifying the Uhthoff phenomenon in the
      pyramidal tract of MS patients. The results suggest that patients with central
      conduction slowing are particularly vulnerable to develop temperature-dependent
      central motor conduction blocks.

PMID- 15465438
TI  - Detection of abnormal cerebral excitability by coincident stimulation and
      recording.
AB  - OBJECTIVE: A method for mapping brain excitability and detecting abnormalities,
      by concurrently stimulating and recording 'focal' compound responses through one
      microelectrode, was evaluated in three rat epilepsy models in comparison with
      distal stimulation of perforant path afferents. METHODS: A fixed trajectory from
      neocortex to dentate gyrus was mapped under halothane anesthesia. Several weeks
      earlier, tetanus toxin or vehicle was microinjected into the dentate polymorphic
      layer, or else rats were genetically epilepsy-prone (GEPR-9) or epilepsy
      resistant (GERR-0). Other (unmapped) rats received acute penicillin
      microinjections within the dentate granular layer. RESULTS: Focal responses,
      although widespread, proved largest in the dentate (>+/-0.5 mV). Tetanus toxin
      diminished focal responses near the microinjection site versus vehicle
      microinjected (66%) or contralateral controls (55%), but enhanced them elsewhere
      in the dentate. It enhanced distal responses at all hippocampal locations. Focal
      but not distal responses were higher in GEPR-9 than in GERR-0 rats at widespread
      forebrain locations (mean 233%). Penicillin facilitated both focal and distal
      dentate responses, but the focal facilitation peaked sooner (about 75 versus 180
      min). CONCLUSIONS: Focal responses better uncover pervasive or discrete
      excitability differences. SIGNIFICANCE: Focal mapping may aid in diagnostic
      imaging and intraoperative targeting, offering high resolution, rapid
      performance, low stimulus currents and minimal invasion.

PMID- 15465439
TI  - Acute repetitive pilomotor seizures (goose bumps) in a patient with right mesial
      temporal sclerosis.
AB  - A 26 year old female with right mesial temporal sclerosis presented with events
      characterized by repetitive piloerection (goose bumps). These events were
      monitored using prolonged video-EEG. The events occurred at a rate of one per
      every 15 min, and were demonstrated to be simple partial seizures of right mesial
      temporal origin. The manifestations included piloerection, cold shivers and ictal
      tachycardia. These were effectively treated with lorazepam. Acute repetitive
      pilomotor seizures are rare. This is the first reported case with right mesial
      temporal sclerosis.

PMID- 15465440
TI  - Entrapment neuropathy of the palmar cutaneous branch of the median nerve in
      carpal tunnel syndrome.
AB  - OBJECTIVE: The aim of this study is to elucidate the significance of
      electrophysiological data of the palmar cutaneous branch of the median nerve
      (PCBm) in the diagnosis entrapment of the PCBm concomitant with carpal tunnel
      syndrome (CTS). MATERIALS AND METHODS: Clinical and electrophysiological studies
      were conducted for abnormal sensation of the thenar eminence in eight CTS
      patients. Sensory nerve action potentials (SNAPs) of the PCBm were recorded from
      bipolar surface electrodes over the forearm using an orthodromic method. The
      preoperative SNAP evaluation was compared with the operative findings. RESULTS:
      The eight patients were divided into two groups based on the characteristics of
      SNAPs of the PCBm; five patients had normal SNAPs of the PCBm and three patients
      had delayed or absent SNAPs. Open surgery confirmed entrapment of the PCBm in one
      patient in the first group and all patients in the latter group. CONCLUSIONS:
      Although clinical symptoms were not always reliable to diagnose entrapment of the
      PCBm in CTS, electrophysiological study of the PCBm was highly sensitive (75%)
      and entirely specific (100%) to demonstrate the entrapment of the PCBm
      preoperatively.

PMID- 15465441
TI  - Diminished central activation during maximal voluntary contraction in chronic
      fatigue syndrome.
AB  - OBJECTIVE: We have investigated whether central activation failure (CAF) is
      increased during local muscle fatigue in chronic fatigue syndrome (CFS). METHODS:
      Fourteen female CFS patients and 14 age-matched healthy female controls made a 2
      min sustained maximal voluntary contraction (MVC) of the biceps brachii muscle.
      Before, during, and after sustained MVC, electrical endplate stimulation was
      applied. Force and 5 channel surface EMG (sEMG) were registered. RESULTS:
      Although force responses upon stimulation during rest did not differ between
      patients and controls, MVC was significantly lower in patients. Already at the
      beginning of sustained MVC, CFS patients showed significantly larger CAF than
      controls (36.5+/-17.0% and 12.9+/-13.3%, respectively). For all individual
      patients mean CAF over the first 45 s was higher than 30%, while it was below 30%
      for all controls. Less peripheral fatigue in patients was demonstrated by the
      changes in muscle fibre conduction velocity and the differences between force
      responses before and after contraction. CONCLUSIONS: Central activation is
      diminished in CFS patients. Possible causes include changed perception, impaired
      concentration, reduced effort and physiologically defined changes, e.g. in the
      corticospinal excitability or the concentration of neurotransmitters. As a
      consequence, demands on the muscle are lower, resulting in less peripheral
      fatigue. SIGNIFICANCE: CFS patients show reduced central activation during MVC.
      The underlying pathophysiological processes remain still to be determined.

PMID- 15465442
TI  - Hyperglycemia alters refractory periods in human diabetic neuropathy.
AB  - OBJECTIVE: To investigate the effects of hyperglycemia on axonal excitability in
      human diabetics. Diabetic nerve dysfunction is partly associated with the altered
      polyol pathway and Na+-K+ ATPase activity, probably resulting in a decrease in
      the trans-axonal Na+ gradient and reduced nodal Na+ currents. METHODS: Threshold
      tracking was used to measure the relative refractory periods (RPs) of median
      motor axons in 58 diabetic patients, 45 normal subjects, and 12 patients with non
      diabetic axonal neuropathy. In diabetic patients, the relationship of RPs with
      hemoglobin A1c (HbA1c) levels was analyzed. RESULTS: The mean RP was similar for
      diabetics and normal controls as a group, but was longer in patients with non
      diabetic neuropathy than in normal controls (P=0.02). Diabetic patients with good
      glycemic control (HbA1c levels <7%) had longer RPs than patients with poorer
      glycemic control and normal controls (P=0.01). RP was longest at the HbA1c level
      of 6%, gradually decreasing and reaching a plateau at the HbA1c level of 8-9%.
      CONCLUSIONS: Hyperglycemia shortens RPs, possibly because metabolic abnormalities
      lead to reduced nodal Na+ currents, and thereby to a lower inactivation of Na+
      channels when generating an action potential. SIGNIFICANCE: RP measurements could
      provide new insights into the ionic pathophysiology of human diabetic neuropathy.

PMID- 15465443
TI  - Improvement of motor performance and modulation of cortical excitability by
      repetitive transcranial magnetic stimulation of the motor cortex in Parkinson's
      disease.
AB  - OBJECTIVE: To assess the effects of focal motor cortex stimulation on motor
      performance and cortical excitability in patients with Parkinson's disease (PD).
      METHODS: Repetitive transcranial magnetic stimulation (rTMS) was performed on the
      left motor cortical area corresponding to the right hand in 12 'off-drug'
      patients with PD. The effects of subthreshold rTMS applied at 0.5 Hz (600 pulses)
      or at 10 Hz (2000 pulses) using a 'real' or a 'sham' coil were compared to those
      obtained by a single dose of l-dopa. The assessment included a clinical
      evaluation by the Unified Parkinson's Disease Rating Scale and timed motor tasks,
      and a neurophysiological evaluation of cortical excitability by single- and
      paired-pulse TMS techniques. RESULTS: 'Real' rTMS at 10 or 0.5 Hz, but not 'sham'
      stimulation, improved motor performance. High-frequency rTMS decreased rigidity
      and bradykinesia in the upper limb contralateral to the stimulation, while low
      frequency rTMS reduced upper limb rigidity bilaterally and improved walking.
      Concomitantly, 10 Hz rTMS increased intracortical facilitation, while 0.5 Hz rTMS
      restored intracortical inhibition. CONCLUSIONS: Low- and high-frequency rTMS of
      the primary motor cortex lead to significant but differential changes in patients
      with PD both on clinical and electrophysiological grounds. The effects on
      cortical excitability were opposite to previous observations made in healthy
      subjects, suggesting a reversed balance of cortical excitability in patients with
      PD compared to normals. However, the underlying mechanisms of these changes
      remain to determine, as well as the relationship with clinical presentation and
      response to l-dopa therapy. SIGNIFICANCE: The present study gives some clues to
      appraise the role of the primary motor cortex in PD. Clinical improvement induced
      by rTMS was too short-lasting to consider therapeutic application, but these
      results support the perspective of the primary motor cortex as a possible target
      for neuromodulation in PD.

PMID- 15465444
TI  - Neuronal activity in the basal ganglia and thalamus in patients with dystonia.
AB  - OBJECTIVE: To explore the role of abnormal neuronal activity in the basal ganglia
      and thalamus in the generation of dystonia. METHODS: Microelectrode recording was
      performed in the globus pallidus internus (GPi), ventral thalamic nuclear group
      ventral oral posterior/ventral intermediate, Vop/Vim) and subthalamic nucleus
      (STN) in patients with primary dystonia (n=11) or secondary dystonia (n=9) during
      surgery. Electromyogram (EMG) was simultaneously recorded in selected muscle
      groups. Single unit analysis and cross-correlations were carried out. RESULTS:
      Three hundred and sixty-seven neurons were obtained from 29 trajectories (GPi:
      13; Vop/Vim: 12; STN: 4), 87% exhibited altered neuronal activity including
      grouped discharges in GPi (n=79) and STN (n=37), long-lasting neuronal activity
      (n=70) and rapid neuronal discharge (n=86) in Vop/Vim. There were neurons in Vop,
      GPi and STN firing at the same frequency as EMG during dystonia (mean: 0.39 Hz,
      range 0.12-0.84 Hz). Significant correlations between neuronal activity and EMG
      at the frequency of dystonia were obtained (GPi: r2=0.7 (n=31), Vop/Vim: r2=0.64
      (n=18) and STN: r2=0.86 (n=17)). CONCLUSIONS: Consistent with previous findings
      of abnormalities observed in Vop/VIM and GPi in relation to dystonia, the present
      data further show that the altered activity in GPi, specifically in dorsal
      subregions of GPi, Vop/Vim and STN is likely to be directly involved in the
      production of dystonic movement. Dystonia-related neuronal activity observed in
      motor thalamus and basal ganglia nuclei of GPi and STN indicates a critical role
      of their interactions affecting both indirect and direct pathways in the
      development of either generalized or focal dystonia. SIGNIFICANCE: These data
      support a central role of the basal ganglia in producing dystonic movements.

PMID- 15465445
TI  - Assessment of central motor conduction to intrinsic hand muscles using the triple
      stimulation technique: normal values and repeatability.
AB  - OBJECTIVE: To establish the triple stimulation technique (TST) for recordings
      from the first dorsal interosseus (FDI) and the abductor pollicis brevis muscles
      (APB), and to analyse the test-retest repeatability of the TST measurements in
      APB. METHODS: The recently developed TST was slightly modified for recordings
      from small hand muscles to account for volume conducted activity from surrounding
      muscles. The TST combines transcranial magnetic stimulation (TMS) with a
      peripheral collision technique [Magistris et al. Brain 121 (1998) 437]. In
      contrast to conventional motor-evoked potentials (MEPs), it quantifies the number
      of conducting central motor neurons (expressed by the TST amplitude ratio, TST
      AR). MEPs and TST were performed in 30 sides of 25 healthy subjects (target
      muscle FDI), and in 29 sides of 21 healthy subjects (target muscle APB). All APB
      recordings were repeated after 25+/-5.9 days. RESULTS: The TST-AR averaged 97.4+/
      2.5% in FDI and 95.9+/-4.7% in APB. There was a mean difference of the TST-AR
      ratio of 2.9+/-3.1% between the repeated APB recordings (95% limits of
      agreement+/-6.3%). CONCLUSIONS: TMS allows activation of virtually all motor
      neurons supplying FDI and APB, when effects of volume conduction are eliminated.
      Its test-retest repeatability is excellent. SIGNIFICANCE: The TST is well suited
      for follow-up examinations of central motor conduction failures. The greater
      number of established target muscles widens its clinical applicability.

PMID- 15465446
TI  - Motor unit excitability changes mediating vestibulocollic reflexes in the
      sternocleidomastoid muscle.
AB  - OBJECTIVE: To investigate the patterns of motor unit firing in single motor units
      from the sternocleidomastoid (SCM) muscles in response to stimuli previously
      shown to be capable of evoking vestibulocollic reflexes (loud clicks and
      electrical stimulation) and to relate these to the previously described surface
      potentials (VEMPs, vestibular evoked myogenic potentials) evoked by the same
      stimuli. METHODS: Eleven male subjects (30-43-years-old) were studied. Local
      anaesthetic was used to block the SCM and confirm that the surface potentials
      (p13n23) arose from it. At another time, fine wire or needle electrodes were used
      to record single motor unit activity and peristimulus time histograms were
      constructed. RESULTS: Local anaesthetic block reduced or abolished the p13n23
      response in 5 of 6 subjects. A total of 94 histograms of motor unit discharges
      were recorded. The excitability changes seen were always small. Loud click
      stimuli given ipsilaterally evoked short latency (mean 14.2 ms, uncorrected for
      triggering delays), and short duration (mean 3.6 ms) inhibition. Contralaterally,
      the effect was excitatory (latency 11.9 ms, uncorrected, mean duration 2.3 ms).
      For electrical stimulation, short latency inhibition occurred ipsilateral to the
      cathode (average latency 14.0 ms, uncorrected, mean duration 2.9 ms) and
      excitation occurred contralaterally. CONCLUSIONS: We confirmed that the SCM is
      the sole or dominant source of the VEMPs recorded from electrodes over it. Short
      latency, short duration motor unit firing changes are evoked in SCM by loud
      clicks and electrical stimulation, stimuli known to be capable of evoking
      vestibulocollic reflexes. VEMPs beginning with a positivity correspond to
      inhibition of the underlying motor unit firing and those starting with a
      negativity correspond to an underlying excitation, findings consistent with
      intracellular recordings of otolith effects. Qualitative explanations of how the
      surface potentials are generated by these excitability changes and relating to
      other properties of the surface responses are proposed. SIGNIFICANCE: This study
      has shown consistent patterns of single motor unit firing which underlie VEMPs
      evoked by both clicks and short duration galvanic stimulation.

PMID- 15465447
TI  - Adolescents with learning disorders have atypical EEG correlation indices. I.
      Correlation indices during visual discrimination.
AB  - OBJECTIVE: To find out whether 14-16-year-old pupils with visual perception
      disabilities have atypical EEG activation patterns during visual discrimination.
      METHODS: EEG correlation indices (EEGCIs), based on the waveform characteristics
      of two EEG signals, were used as measures of slow joint activation of cortical
      regions during visual discrimination in pupils with visual perception
      disabilities. RESULTS: During visual discrimination low EEGCIs were seen between
      the left temporal and both parieto-occipital EEG channels in pupils with visual
      perception disabilities and in pupils with a poor occupational outcome. The
      pupils with low performance intelligence and those with difficulties in the
      visual discrimination task had low EEGCIs within the left hemisphere. The left
      hemispheric dominance of the findings is suggested to reflect the
      psychophysiology of the task since visual discrimination demands attention to
      details (local processing) and is thus supposed to be more strongly represented
      in the left hemisphere. CONCLUSIONS: During visual discrimination, low EEGCIs
      were seen in the posterior and left hemispheric regions of pupils with
      disabilities in visual perception and visual discrimination and with a poor
      occupational outcome. SIGNIFICANCE: Low EEGCIs in posterior and left hemispheric
      regions during visual discrimination can to some extent be seen as
      neurophysiological markers for visual perception disabilities and a poor
      occupational outcome and imply an increased need for adjustment of the
      educational curriculum and a need for occupational guidance.

PMID- 15465448
TI  - Adolescents with learning disorders have atypical EEG correlation indices. II.
      Correlation indices during reading.
AB  - OBJECTIVE: To find out whether 14-16 year old reading and writing impaired pupils
      have atypical EEG activation patterns during reading. METHODS: EEG correlation
      indices (EEGCIs), based on the waveform characteristics of two EEG signals, were
      used as measurers of slow joint activation of cortical regions during reading in
      pupils with reading and writing impairment. RESULTS: Reading was associated with
      high EEGCIs within the right hemisphere in reading and writing impaired pupils.
      The finding is analogous to the results of an earlier study [Byring,
      Electroencephalogr. Clin. Neurophysiol. 63 (1986) 1] in boys with spelling
      disabilities. The activation in the right hemisphere might represent a
      compensation for a left hemisphere dysfunction in pupils with reading and writing
      impairment during reading, as suggested by a number of functional neuroimaging
      studies. This interpretation was corroborated by high EEGCIs especially in those
      impaired pupils who had a good occupational outcome. CONCLUSIONS: EEGCIs during
      reading are high within the right hemisphere in pupils with reading and writing
      impairment. SIGNIFICANCE: High EEGCIs within the right hemisphere during reading
      might be considered neurophysiological markers for reading and writing
      impairment.

PMID- 15465449
TI  - Event-related potentials in the auditory oddball as a function of EEG alpha phase
      at stimulus onset.
AB  - OBJECTIVE: We aimed to examine the relation between the phase of
      electroencephalogram (EEG) alpha activity at stimulus onset and event-related
      potentials (ERPs) in a fixed-inter-stimulus interval auditory 'oddball' task,
      using a novel conceptualisation of orthogonal phase effects (cortical negativity
      versus positivity, negative driving versus positive driving, waxing versus
      waning). METHODS: EEG responses to button-press targets, from 14 subjects
      presented with 4 blocks of 150 stimuli (50% target probability), were examined.
      Pre-stimulus alpha activity (8-13 Hz) at Pz was assessed for each trial by
      digital filtering of the EEG. The alpha cycle at Pz, starting from a negative
      going zero crossing, was used to sort trials into 4 phases, for which ERPs were
      derived from both the filtered and unfiltered EEG activity at Fz, Cz, and Pz.
      RESULTS: Preferred brain states in this paradigm were indicated by an 8% greater
      occurrence of negative driving than positive driving, and a 33% greater
      occurrence of waxing than waning phases. Negative driving phases were associated
      with increased N1 latencies and decreased N2 amplitudes. Latencies of N1 and P2
      were reduced in waxing phases. These reflected systematic changes in alpha
      frequency and amplitude at stimulus onset. CONCLUSIONS: In a fixed-inter-stimulus
      interval paradigm, component frequencies of the EEG are dynamically adjusted in
      order to provide brain states at the moment of stimulus presentation which
      differentially affect the EEG correlates of stimulus processing. SIGNIFICANCE:
      The results add to our understanding of the genesis of the ERP, indicating the
      importance of the dynamic interplay between instantaneous EEG activity and
      stimulus processing reflected in the ERP.

PMID- 15465450
TI  - Age-related differences in auditory event-related potentials during a cued
      attention task.
AB  - OBJECTIVE: To determine if aging is associated with differences in attentional
      regulation using behavioral and event-related potential (ERP) measures. METHODS:
      Younger (n=13;M=20 years) and older (n=12;M=76 years) subjects performed an
      auditory cued attention task. Verbal cues correctly (valid) or incorrectly
      (invalid) predicted the ear receiving a target tone 1.5 s later, or were
      uninformative (neutral). Targets were either 'high' (2000 Hz) or 'low' (1000 Hz)
      pitch monaural tones. Subjects pressed one of 4 buttons to indicate target ear
      and pitch. ERPs following cues and targets (P50, N100, P200, slow waves), and
      negative slow potentials (CNV) between cues and targets were assessed. RESULTS:
      Cue information had significant effects on reaction time for both groups
      (valid<neutral<invalid). Target N100 amplitude was significantly affected by
      cueing in younger (invalid>valid) but not older subjects. Target slow waves were
      also affected by cue information (invalid>valid), and the difference was larger
      and lasted longer in older subjects. Slow waves following cues were significantly
      larger in older subjects, but the subsequent CNV amplitudes were comparable among
      groups. CONCLUSIONS: When performing a cued attention task, age differences are
      present in transient ERPs following cues and targets. SIGNIFICANCE: Age
      differences in ERPs associated with attentional regulation support the hypothesis
      that attentional changes contribute to cognitive aging.

PMID- 15465451
TI  - Resource allocation and somatosensory P300 amplitude during dual task: effects of
      tracking speed and predictability of tracking direction.
AB  - OBJECTIVE: The amount of attentional resources allocated to a task is determined
      by the intrinsic demands, also denoted as task load or difficulty of the task.
      Effects of resource allocation on the somatosensory N140 and P300 were
      investigated in an inter-modal situation using a dual-task methodology. METHODS:
      Under a dual-task condition, subjects concurrently performed a visuomotor
      tracking task and a somatosensory oddball task, while they performed just the
      oddball task under an oddball-only condition. In the tracking task, the subjects
      tracked the target line, which was presented on an oscilloscope and automatically
      moved, with the line which represented their own force generated by grip movement
      with the left hand. Tracking speed (experiment 1) and tracking predictability
      (experiment 2) were manipulated to vary task difficulty. N140, P300, and reaction
      time (RT) in the oddball task and tracking accuracy in the tracking task were
      measured. RESULTS: The P300 and N140 amplitudes were reduced in the dual-task
      condition compared to those in the oddball-only condition. The fastest tracking
      speed produced lower tracking accuracy and later RT. However, the tracking speed
      did not affect the P300 or N140 amplitudes. In contrast, the P300 amplitude was
      smaller when the change in tracking direction was unpredictable than when it was
      predictable, without any differences in tracking accuracy or RT, N140.
      CONCLUSIONS: The differences in behaviors among N140, P300, and RT following
      manipulation of task difficulty support the multiple-resource hypothesis, which
      defines functionally separate pools of resources. SIGNIFICANCE: The present study
      may show that the P300 amplitude reflects modality-unspecific resource at more
      central level, and that the N140 amplitude involves perceptual resource.

PMID- 15465452
TI  - Adelta nociceptor response to laser stimuli: selective effect of stimulus
      duration on skin temperature, brain potentials and pain perception.
AB  - OBJECTIVE: To disclose a possible effect of duration of pulsed laser heat stimuli
      on Adelta nociceptor responses, skin temperature profiles, brain evoked
      potentials and pain perception. METHODS: We used a laser stimulator which works
      in the millisecond range and allows us to change the duration of the pulse while
      keeping the total energy of the stimulus constant. In 10 healthy volunteers, we
      measured the intensity of perceived pain with a 0-10 scale and the latency and
      amplitude of the early N1 and late N2 components of the scalp potentials evoked
      by laser pulses of equal energy and three different stimulus durations (2, 10,
      and 20 ms). Using a specifically developed pyrometer with a temporal resolution
      lower than 1 ms we also measured stimulus-induced changes of skin temperature.
      RESULTS: Stimulus duration significantly influenced temperature rise times, pain
      perception, and brain potentials. Shorter stimulus durations yielded steeper
      slopes in the skin temperature profiles and higher pain ratings, shortened the
      latency of the N1 and N2 components, and increased the amplitude of N1.
      CONCLUSIONS AND SIGNIFICANCE: The shorter stimulus duration shortens receptor
      activation times and yields a more synchronous afferent volley, thus providing a
      stronger spatial-temporal summation at central synapses that enhances intensity
      of first pain and brain potentials. This may prove useful in clinical
      applications.

PMID- 15465453
TI  - Functional connectivity between forearm and digits representations in human
      somatosensory area 3b.
AB  - OBJECTIVE: We compared the effects of tactile interference to the forearm on
      magnetic responses evoked by electric stimulation of the little finger (D5) and
      the thumb (D1). METHODS: Electric stimulation was delivered to D5 or D1
      individually. In each stimulus session, magnetic recordings were conducted with
      or without concurrent tactile interference to the radial side of the anterior
      forearm. RESULTS: With forearm interference, the amplitude of the primary
      response (N20m) following D5 stimulation was reduced to 90.7% of the control
      value without interference, while that following D1 stimulation was not affected
      (100.7%). CONCLUSIONS: In human somatosensory area 3b, the representation of the
      forearm is immediately adjacent to that of the D5, and distant from that of the
      D1. Thus, the result suggests that the tactile interference effect on N20m
      depends on the cortical distance between electrically and mechanically activated
      3b areas. SIGNIFICANCE: Intrinsic synaptic connections between the 3b hand
      representation and its surroundings have been hypothesized as a neural basis for
      plastic changes of the human brain, such as a phantom hand phenomenon. The
      present finding implies that these connections may play some physiological roles
      even in normal adult humans.

PMID- 15465454
TI  - N10 component in median nerve somatosensory evoked potentials (SEPs) is not an
      antidromic motor potential.
AB  - OBJECTIVE: To test the hypothesis that the N10 far-field potential in median
      nerve somatosensory evoked potentials is generated by the motor axons by
      examining patients with amyotrophic lateral sclerosis (ALS). METHODS: Subjects
      were 5 ALS patients showing pronounced or complete denervation of median
      innervated small hand muscles. We evaluated N10 over scalp, and proximal plexus
      volleys (PPVs) at lateral or anterior cervical electrode. RESULTS: N10 and PPVs
      were definitely preserved for every ALS subject. N10 amplitudes of ALS subjects
      were even significantly larger than control subjects. In one ALS patient
      completely lacking motor axons, N10 was larger than the largest one among control
      subjects. CONCLUSIONS: Present results clearly indicate that N10 is not
      predominantly generated by motor axons but by the whole median nerve dominated by
      sensory axons. We propose a theory that N10 is a junctional potential generated
      by the entrance of the median nerve into bone at the intervertebral foramen,
      producing a positive pole at the non-cephalic reference electrode. Significantly
      larger N10 in ALS subjects may be due to the lack of cancellation by slower motor
      axons. SIGNIFICANCE: The hypothesis that N10 is generated by motor axons is
      refuted, and a new theory of its generation is presented.

PMID- 15465455
TI  - Comparison of pupil responses to luminance and colour in severe optic neuritis.
AB  - OBJECTIVE: The pupil response to light flux increments is abnormal in severe
      optic neuritis, but little is known about the effects of this condition on the
      pupil colour response. The aim of this study was to examine how optic neuritis
      affects pupil responses to light flux and colour modulation and the extent to
      which such pupil responses mirror the loss and recovery of vision. METHODS: A new
      pupil examination technique that makes use of sinusoidal modulation of either
      luminance contrast or chromatic saturation was employed. This technique enables
      the automatic extraction of both pupil response amplitude and latency and
      achieves a high signal to noise ratio with fewer averages. RESULTS: The study
      reveals a greater loss of pupil response amplitude and significantly longer
      latencies to chromatic modulation (i.e. approximately 80 ms). Stimulation of the
      unaffected eye in the optic neuritis group results in smaller response amplitudes
      when compared to the normal group for both light flux and colour modulation.
      CONCLUSIONS: Pupil response components can be affected differently in optic
      neuritis. These findings suggest that the pupil colour response, in particular,
      may provide a useful, objective estimator to judge the extent of damage and
      recovery in diseases of the optic nerve.

PMID- 15465456
TI  - Simulated nystagmus suppresses pattern-reversal but not pattern-onset visual
      evoked potentials.
AB  - OBJECTIVE: The aim of this study is to quantify and compare the effects of
      simulated horizontal nystagmus on pattern-reversal and pattern-onset visual
      evoked potentials (VEPs). METHODS: In eight visually normal subjects with normal
      oculomotor behaviour, we monitored eye movements and recorded pattern-reversal
      and pattern-onset VEPs from occipital electrodes. Subjects viewed the stimulus
      monocularly via a mirror, which was placed close to the eye and driven by a
      scanner at four different amplitudes (0, 1, 2, and 3 degrees ) with a 4 Hz saw
      tooth waveform to simulate horizontal jerk-nystagmus. RESULTS: Retinal image
      motion nearly abolished the pattern-reversal VEPs (maximal reduction by 85%; mean
      reduction by 72%, P<0.001), while there was a non-significant reduction (mean
      reduction by 15%) of the pattern-onset VEPs. CONCLUSIONS: The differential effect
      of simulated nystagmus on pattern-reversal and pattern-onset VEPs resembles that
      reported in studies on nystagmus patients. We conclude that the interaction of
      retinal image motion with the stimulus is sufficient to explain the reduction of
      pattern-reversal VEPs in patients with nystagmus and propose simulated nystagmus
      as a useful tool to test the influence of nystagmus on the efficiency of VEP
      stimuli. SIGNIFICANCE: This study demonstrates how horizontal jerk-nystagmus can
      be simulated and suggests possible mechanisms by which nystagmus reduces VEP
      responses.

PMID- 15465457
TI  - Prevention at a cost.

PMID- 15465459
TI  - Malignant pleural mesothelioma: time for translational research.

PMID- 15465460
TI  - Professional skills and shared consent in paediatric research.

PMID- 15465461
TI  - Merkel-cell carcinoma of the skin.
AB  - Merkel-cell carcinoma (MCC) is a rare form of skin cancer of neuroendocrine
      origin that has been described as the most aggressive cutaneous malignancy. The
      cell of origin is thought to be the Merkel cell or skin-pressure receptor. It has
      the propensity for dermal-lymphatic invasion, and nodal and haematogenous spread.
      Factors that have been implicated in its cause include exposure to sunlight and
      immunosuppression. The tumour has many similarities to small-cell carcinoma of
      the lung, with intrinsic sensitivity to ionising radiation and chemotherapy, and
      an aggressive metastatic potential. The best treatment outcomes can be achieved
      with early diagnosis and the integration of surgery, radiation, and chemotherapy.
      The treatment challenges for the clinician are often enormous because many of the
      patients are elderly and because lesions occur in difficult sites such as the
      head and neck region and the lower leg.

PMID- 15465462
TI  - Retromolar mass as manifestation of multiple myeloma.

PMID- 15465463
TI  - Colorectal cancer and inherited mutations in base-excision repair.
AB  - Polyposis associated with mutations in the gene MUTYH is an autosomal recessive
      syndrome characterised by the development of multiple colorectal adenomas and
      cancer. It is the first cancer-predisposition disorder to be associated with
      defects in the pathway of base-excision repair. We review our knowledge to date
      of the disease, discuss base-excision repair in relation to cellular defence
      against oxidative damage, and give an overview of the molecular genetics and
      clinicopathological features of tumours associated with MUTYH mutations. No
      longer a research finding, genetic testing for MUTYH is now a necessary part of
      molecular diagnosis in familial cancer clinics throughout Australia and the UK.
      Current recommendations for the screening and management of the disease are also
      discussed.

PMID- 15465464
TI  - Assessment of therapeutic response in patients with metastatic bone disease.
AB  - Metastatic bone disease is common in cancer patients and causes substantial
      disease-related morbidity and mortality. However, several effective treatments
      are available for the management of these patients. Bisphosphonates, which
      inhibit osteoclast-mediated resorption of bone matrix, are especially important
      because they decrease the incidence of skeletal-related events in many tumour
      types and can complement antineoplastic therapies. At present, assessment of
      treatment for bone metastases is hindered by a lack of effective, rapid methods
      to measure disease response. We discuss the difficulties of current measures of
      response assessment and describe the development of new radiological and
      biochemical markers of bone metastases. Assays that detect type I collagen
      telopeptides as markers of bone resorption seem to be most promising at present.

PMID- 15465465
TI  - Stress, depression, the immune system, and cancer.
AB  - The links between the psychological and physiological features of cancer risk and
      progression have been studied through psychoneuroimmunology. The persistent
      activation of the hypothalamic-pituitary-adrenal (HPA) axis in the chronic stress
      response and in depression probably impairs the immune response and contributes
      to the development and progression of some types of cancer. Here, we overview the
      evidence that various cellular and molecular immunological factors are
      compromised in chronic stress and depression and discuss the clinical
      implications of these factors in the initiation and progression of cancer. The
      consecutive stages of the multistep immune reactions are either inhibited or
      enhanced as a result of previous or parallel stress experiences, depending on the
      type and intensity of the stressor and on the animal species, strain, sex, or
      age. In general, both stressors and depression are associated with the decreased
      cytotoxic T-cell and natural-killer-cell activities that affect processes such as
      immune surveillance of tumours, and with the events that modulate development and
      accumulation of somatic mutations and genomic instability. A better understanding
      of the bidirectional communication between the neuroendocrine and immune systems
      could contribute to new clinical and treatment strategies.

PMID- 15465466
TI  - Harnessing the potential of cancer genetics in healthcare.
AB  - The advancement of knowledge in genetics will have a profound effect on
      prediction, prevention, and treatment of cancer. It has the potential to offer
      more personalised healthcare that accords with an individual's genetic profile.
      However, the complex medical, ethical, legal, and psychosocial issues brought by
      our ability to test healthy individuals for cancer predisposition and the fast
      pace of advances in genetics pose great challenges to the medical community.
      Individuals and families are unlikely to benefit from an effective and ethical
      application of new genetic knowledge unless high quality cancer-genetics services
      are developed and integrated into mainstream healthcare, more research is
      undertaken into the prevention, causes, and treatment of cancer, and further
      efforts are made to improve public understanding and acceptance of cancer
      genetics.

PMID- 15465467
TI  - Severe hypercalcaemia from secretion of parathyroid hormone-related peptide.

PMID- 15465468
TI  - Primary cardiac angiosarcoma treated with carbon-ion radiotherapy.

PMID- 15465469
TI  - Believe me, I'm a doctor.

PMID- 15465471
TI  - Industrial solvents and psychological effects.
AB  - Organic solvents are widely used in industries for cleaning, degreasing, and
      other processes. The high dose neurotoxicity of occupational solvents is evident,
      and the existence of residual effects following lower dose exposure remains a
      focus of interest 30 years after initial reports of behavioral changes in
      painters from the Scandinavian literature. This article reviews recent studies on
      occupational solvent exposure and neuropsychological outcomes. The methodologic
      difficulties facing studies and the role of neuroimaging in solvent neurotoxicity
      investigations are examined. Existing studies consistently demonstrate
      association between exposure and neurobehavioral outcomes, but the specificity of
      the findings is less impressive. Threshold levels are uncertain. A safe and
      achievable threshold level seems possible from the current literature;
      unfortunately, such exposure limits have not yet been established by current
      studies. Several frequently encountered chemicals are discussed.

PMID- 15465472
TI  - Neurologic issues with solvents.
AB  - Reports of injury began after the introduction of chlorinated solvents in the
      1920s. In 1987, the National Institute for Occupational Safety and Health
      reported that 9.8 million workers were exposed to organic solvents in
      occupational settings, with most of these exposures being to mixtures of
      solvents. Although solvent mixtures have been noted to be responsible for
      neuropathy, seizures, and encephalopathy, identifying the culpable agent has been
      difficult, because the associations between many solvents and their biologic
      effects have not been well defined, and solvent interaction in mixtures have not
      been well or easily characterized. In some cases, these exposures have been
      estimated to be below levels designated in regulations as acceptable for workers.

PMID- 15465473
TI  - Solvents and the skin.
AB  - In this paper, we examine how skin structure affects the ability of solvents to
      irritate and permeate the skin; the patterns of cutaneous injury caused by
      solvents; the effects of specific solvents on the skin; and the potential for
      systemic toxicity from dermal absorption.

PMID- 15465474
TI  - Hepatorenal solvent toxicology.
AB  - The liver and kidneys are tissues with a rich blood supply. Thus, with
      significant exposures, these tissues may be at risk for anatomic or
      pathophysiologic alterations. It is important to understand the gross,
      microscopic, and functional anatomy of these important organs to analyze
      potential adverse effects of solvents.

PMID- 15465475
TI  - Research on machine learning issues in biomedical informatics modeling.

PMID- 15465476
TI  - Classification and knowledge discovery in protein databases.
AB  - We consider the problem of classification in noisy, high-dimensional, and class
      imbalanced protein datasets. In order to design a complete classification system,
      we use a three-stage machine learning framework consisting of a feature selection
      stage, a method addressing noise and class-imbalance, and a method for combining
      biologically related tasks through a prior-knowledge based clustering. In the
      first stage, we employ Fisher's permutation test as a feature selection filter.
      Comparisons with the alternative criteria show that it may be favorable for
      typical protein datasets. In the second stage, noise and class imbalance are
      addressed by using minority class over-sampling, majority class under-sampling,
      and ensemble learning. The performance of logistic regression models, decision
      trees, and neural networks is systematically evaluated. The experimental results
      show that in many cases ensembles of logistic regression classifiers may
      outperform more expressive models due to their robustness to noise and low sample
      density in a high-dimensional feature space. However, ensembles of neural
      networks may be the best solution for large datasets. In the third stage, we use
      prior knowledge to partition unlabeled data such that the class distributions
      among non-overlapping clusters significantly differ. In our experiments, training
      classifiers specialized to the class distributions of each cluster resulted in a
      further decrease in classification error.

PMID- 15465477
TI  - Comprehensive vertical sample-based KNN/LSVM classification for gene expression
      analysis.
AB  - Classification analysis of microarray gene expression data has been widely used
      to uncover biological features and to distinguish closely related cell types that
      often appear in the diagnosis of cancer. However, the number of dimensions of
      gene expression data is often very high, e.g., in the hundreds or thousands.
      Accurate and efficient classification of such high-dimensional data remains a
      contemporary challenge. In this paper, we propose a comprehensive vertical sample
      based KNN/LSVM classification approach with weights optimized by genetic
      algorithms for high-dimensional data. Experiments on common gene expression
      datasets demonstrated that our approach can achieve high accuracy and efficiency
      at the same time. The improvement of speed is mainly related to the vertical data
      representation, P-tree,Patents are pending on the P-tree technology. This work is
      partially supported by GSA Grant ACT#:K96130308. and its optimized logical
      algebra. The high accuracy is due to the combination of a KNN majority voting
      approach and a local support vector machine approach that makes optimal decisions
      at the local level. As a result, our approach could be a powerful tool for high
      dimensional gene expression data analysis.

PMID- 15465478
TI  - Cancer classification and prediction using logistic regression with Bayesian gene
      selection.
AB  - In microarray-based cancer classification and prediction, gene selection is an
      important research problem owing to the large number of genes and the small
      number of experimental conditions. In this paper, we propose a Bayesian approach
      to gene selection and classification using the logistic regression model. The
      basic idea of our approach is in conjunction with a logistic regression model to
      relate the gene expression with the class labels. We use Gibbs sampling and
      Markov chain Monte Carlo (MCMC) methods to discover important genes. To implement
      Gibbs Sampler and MCMC search, we derive a posterior distribution of selected
      genes given the observed data. After the important genes are identified, the same
      logistic regression model is then used for cancer classification and prediction.
      Issues for efficient implementation for the proposed method are discussed. The
      proposed method is evaluated against several large microarray data sets,
      including hereditary breast cancer, small round blue-cell tumors, and acute
      leukemia. The results show that the method can effectively identify important
      genes consistent with the known biological findings while the accuracy of the
      classification is also high. Finally, the robustness and sensitivity properties
      of the proposed method are also investigated.

PMID- 15465479
TI  - Discovering significant and interpretable patterns from multifactorial DNA
      microarray data with poor replication.
AB  - MOTIVATION: Multivariate analyses are advantageous for the simultaneous testing
      of the separate and combined effects of many variables and of their interactions.
      In factorial designs with many factors and/or levels, however, sufficient
      replication is often prohibitively costly. Furthermore, complicated statements
      are often required for the biological interpretation of the higher-order
      interactions determined by standard statistical techniques like analysis of
      variance. RESULTS: Because we are usually interested in finding factor-specific
      effects or their interactions, we assumed that the observed expression profile of
      a gene is a manifestation of an underlying factor-specific generative pattern
      (FSGP) combined with noise. Thus, a genetic algorithm was created to find the
      nearest FSGP for each expression profile. We then measured the distance between
      each profile and the corresponding nearest FSGP. Permutation testing for the
      distance measures successfully identified those genes with statistically
      significant profiles, thus yielding straightforward biological interpretations.
      Association networks of genes, drugs, and cell lines were created as tripartite
      graphs, representing significant and interpretable relations, by using a
      microarray experiment of gastric-cancer cell lines with a factorial design and no
      replication. The proposed method may benefit the combined analysis of
      heterogeneous expression data from the growing public repositories.

PMID- 15465480
TI  - Induction of comprehensible models for gene expression datasets by subgroup
      discovery methodology.
AB  - Finding disease markers (classifiers) from gene expression data by machine
      learning algorithms is characterized by a high risk of overfitting the data due
      the abundance of attributes (simultaneously measured gene expression values) and
      shortage of available examples (observations). To avoid this pitfall and achieve
      predictor robustness, state-of-the-art approaches construct complex classifiers
      that combine relatively weak contributions of up to thousands of genes
      (attributes) to classify a disease. The complexity of such classifiers limits
      their transparency and consequently the biological insights they can provide. The
      goal of this study is to apply to this domain the methodology of constructing
      simple yet robust logic-based classifiers amenable to direct expert
      interpretation. On two well-known, publicly available gene expression
      classification problems, the paper shows the feasibility of this approach,
      employing a recently developed subgroup discovery methodology. Some of the
      discovered classifiers allow for novel biological interpretations.

PMID- 15465481
TI  - A greedy algorithm for supervised discretization.
AB  - We present a greedy algorithm for supervised discretization using a metric
      defined on the space of partitions of a set of objects. This proposed technique
      is useful for preparing the data for classifiers that require nominal attributes.
      Experimental work on decision trees and naive Bayes classifiers confirm the
      efficacy of the proposed algorithm.

PMID- 15465482
TI  - A primer on gene expression and microarrays for machine learning researchers.
AB  - Data originating from biomedical experiments has provided machine learning
      researchers with an important source of motivation for developing and evaluating
      new algorithms. A new wave of algorithmic development has been initiated with the
      publication of gene expression data derived from microarrays. Microarray data
      analysis is particularly challenging given the large number of measurements
      (typically in the order of thousands) that are reported for relatively few
      samples (typically in the order of dozens). Many data sets are now available on
      the web. It is important that machine learning researchers understand how data
      are obtained and which assumptions are necessary in the analysis. Microarray data
      have the potential to cause significant impact in machine learning research, not
      just as a rich and realistic source of cases for testing new algorithms, as has
      been the UCI machine learning repository in the past decades, but also as a main
      motivation for their development. In this article, we briefly review the biology
      underlying microarrays, the process of obtaining gene expression measurements,
      and the rationale behind the common types of analyses involved in a microarray
      experiment. We outline the main challenges and reiterate critical considerations
      regarding the construction of supervised learning models that use this type of
      data. The goal of this article is to familiarize machine learning researchers
      with data originated from gene expression microarrays.

PMID- 15465483
TI  - Foxc2 is expressed in developing lymphatic vessels and other tissues associated
      with lymphedema-distichiasis syndrome.
AB  - The molecular events involved in lymphatic development are poorly understood.
      Hence, the genes responsible for hereditary lymphedema are of great interest due
      to the potential for providing insights into the mechanisms of lymphatic
      development, the diagnosis, prevention and treatment of lymphedema, and
      lymphangiogenesis during tumor growth. Mutations in the FOXC2 transcription
      factor cause a major form of hereditary lymphedema, the lymphedema-distichiasis
      syndrome. We have conducted a study of Foxc2 expression during mouse development
      using immunohistochemistry, and examined its expression in lymphatics compared to
      its paralog Foxc1 and to Vegfr-3, Prox1 and other lymphatic and blood vascular
      proteins. We have found that Foxc2 is expressed in lymphatic primordia, jugular
      lymph sacs, lymphatic collectors and capillaries, as well as in podocytes,
      developing eyelids and other tissues associated with abnormalities in lymphedema
      distichiasis syndrome.

PMID- 15465484
TI  - Identification of the facilitative glucose transporter 12 gene Glut12 in mouse
      preimplantation embryos.
AB  - In this study we report the cloning and characterisation of the mouse Glut12 gene
      and examine for the first time its expression pattern in the earliest stages of
      development. Mouse Glut12 (mGlut12) was cloned from preimplantation embryos by
      5'RACE RT-PCR using primers designed from an EST clone corresponding to a human
      GLUT12 antigenic sequence after positive immunoreactivity was observed in mouse
      two-cell embryos by western immunoblotting. The mGlut12 gene contains an open
      reading frame of 1869 base pairs, potentially encoding a polypeptide of 622 amino
      acids. The predicted mGLUT12 protein bears all the hallmarks of the SLC2A family
      of hexose transporters and shares an 83% sequence homology to human GLUT12.
      Consistent with its human homolog mGlut12 mRNA is found highly expressed in
      skeletal and cardiac muscle and fat. Additionally, it was also found in the
      uterus and during early embryogenesis. During early development in the mouse,
      Glut12 expression is clearly apparent in ovulated oocytes and two-cell embryos
      but declines in day 3 morulae. With the exception of some Glut12 expression
      apparent in blastocysts, Glut12 mRNA remains at low to undetectable levels until
      E11.

PMID- 15465485
TI  - Expression of Stra13 during mouse endochondral bone development.
AB  - We have examined the expression of the basic helix-loop-helix factor Stra13
      (DEC1/Sharp2) during endochondral bone development in the mouse. Stra13
      expression was examined by in situ hybridization in the tibia from E14.5-E18.5,
      and at post-natal day 24. At E14.5, expression of Stra13 mRNA was very low, with
      expression limited to scattered hypertrophic chondrocytes. At E15.5 Stra13 mRNA
      was present in post-mitotic hypertrophic chondrocytes, co-localizing with
      collagen X expression. At E16.5-E18.5, Stra13 was expressed in both the
      proliferating chondrocytes and in the late hypertrophic chondrocytes. At E15.5
      E18.5, Stra13 expression was also observed in the primary spongiosa. Stra13
      expression was also maintained in the 24-day post-natal tibia, with expression
      detectable only in the late hypertrophic chondrocytes. Because Stra13 has been
      shown to be induced by hypoxia, and the growth plate is hypoxic during embryonic
      development, we compared the expression pattern of Stra13 and the HIF1-alpha
      target gene VEGF. VEGF is expressed predominantly in the late hypertrophic
      chondrocytes, with lower expression in the proliferating chondrocytes. Thus,
      there was a large degree of overlap in the expression patterns of Stra13 and VEGF
      in chondrocytes during embryonic development.

PMID- 15465486
TI  - Expression of fascin-1, the gene encoding the actin-bundling protein fascin-1,
      during mouse embryogenesis.
AB  - Fascin-1 is an actin-bundling protein that contributes to the architecture and
      function of cell protrusions and microfilaments in cell adhesion, interactions
      and motility. Fascin-1 has been studied in cultured cells and by biophysical
      methods, but little is known about its distribution and functions in vertebrate
      development. As a first step to understanding the role of fascin-1 in
      embryogenesis, we have characterised the expression pattern of fascin-1 by in
      situ hybridisation on whole-mount and sectioned mouse embryos from embryonic day
      (E)8.0-E16.5. Fascin-1 was widely expressed throughout the embryo and the
      developing nervous system and mesenchymal tissues represented major sites of
      expression. Intense signals were observed in different regions of the brain, in
      the spinal cord and retina, and the cranial and dorsal root ganglia (DRG)
      appeared strongly positive. This neural expression remained strong throughout
      development. Fascin-1 was also present in the developing somites. High expression
      was detected in branchial arches and limb bud mesenchyme. At later stages, fascin
      1 was expressed in different muscles of the face, skeletal muscles of the body,
      and in smooth muscle layers of several organs. Limb tendons appeared strongly
      positive. There was weak expression in heart ventricles. These results show that
      fascin-1 is principally expressed in neural and mesenchymal derivatives during
      embryonic development.

PMID- 15465487
TI  - Selective expression of a sec1/munc18 member in sea urchin eggs and embryos.
AB  - Regulated secretion is mediated by SNAREs (soluble NSF attachment receptors) and
      their regulators and effectors, which include the SM (sec1/munc18) family of
      proteins. Homologs of the SNAREs have been identified in sea urchins, associated
      with cortical granule exocytosis at fertilization, with membranes of the cleavage
      furrow, and in secretory cells later in development. To contribute to the
      understanding of regulated secretion in sea urchins we have cloned the single SM
      protein homolog from two species of sea urchin, Lytechinus variegatus and
      Strongylocentrotus purpuratus. In oocytes and eggs, we find that it localizes to
      the plasma membrane and the cortical region of the egg, consistent with a role in
      one of the steps leading to cortical granule exocytosis. The protein is also
      expressed throughout development, enriched in membranes of the cleavage furrow in
      early embryos, and in cells of the gut in advanced embryos. Furthermore, we find
      that sec1/munc18 co-localizes with its cognate binding partner syntaxin. Finally,
      our biochemical analysis shows that the protein associates with rab3 in high
      molecular weight complexes, suggesting that the exocytotic machinery functions as
      a multi-protein subunit to mediate regulated secretion in sea urchins. These
      results will be instrumental in the future to functionally test the SNARE
      regulators associated with multiple membrane fusion events.

PMID- 15465488
TI  - Otx2, Gbx2, and Fgf8 expression patterns in the chick developing inner ear and
      their possible roles in otic specification and early innervation.
AB  - The chick inner ear is a complex structure containing auditory and vestibular
      sensory organs innervated by neurons of the acoustic-vestibular ganglion. The
      molecular signals involved in the specification and initial innervation of the
      otic epithelium are poorly understood. Here, we present a detailed description of
      the Otx2, Gbx2, and Fgf8 gene expression patterns in the chick developing inner
      ear, comparing them with the Bmp4 expression, a putative sensory-organ marker.
      The Otx2 expression was detected in the ventro-lateral wall of the otic anlage
      and could play a role in the segregation of the saccule and utricle maculae. The
      relationship between Gbx2 and Fgf8 expression changed during inner ear
      development but was always related to the macula sacculi innervation and
      endolymphatic duct formation. Our results also suggest that the maculae of the
      saccule and lagena, and the medial portion of the macula utriculi could arise
      within a broad Fgf8-positive domain previously observed at the otocyst stage. The
      spatial and temporal relationships between these gene expression domains and the
      initial innervation of the epithelium by some subpopulations of otic axons
      suggest that expression domain boundaries could be involved in the specification
      and early innervation of presumptive sensory patches.

PMID- 15465489
TI  - Hox/Pbx and Brn binding sites mediate Pax3 expression in vitro and in vivo.
AB  - Pax3 is a paired-homeodomain class transcription factor that serves a role in
      dorsal-ventral and medial-lateral patterning during vertebrate embryogenesis. Its
      expression is localized to dorsal domains within the developing neural tube and
      lateral domains within the developing somite. Additionally, modulation of its
      expression occurs along the rostral-caudal axis. Previous studies [Development
      124 (1997) 617] have localized sequence elements required for expression of Pax3
      in the neural tube and neural crest to a 1.6 kbp promoter fragment. In the
      present study, four discrete DNA elements within the 1.6 kbp promoter fragment
      are shown by electrophoretic mobility shift assays (EMSA) to exhibit sequence
      specific interactions with proteins present in nuclear extracts from P19 EC cells
      induced to express Pax3 by treatment with retinoic acid (RA). Proteins
      interacting at each of these elements are identified based on biochemical
      purification using DNA affinity chromatography or a candidate approach. These
      identifications were confirmed by the ability of specific antibodies to super
      shift DNA-protein complexes in EMSA. Two of the four DNA sequence elements are
      shown to interact with the neural specific Pou-domain class III transcription
      factors Brn1 and Brn2. The remaining sites contain either consensus binding
      elements for heterodimers of Pbx and an anterior set of Hox family members, from
      paralogous groups 1-5, or monomeric Meis and are shown to interact with members
      of the Pbx and Meis families. Ectopic expression of Brn2 plus HoxA1 but not
      either factor alone, is sufficient to induce efficient expression from the
      endogenous Pax3 promoter in P19 EC stem cells under conditions where they would
      not otherwise express Pax3. Finally, in transgenic mice, mutation of either of
      the Pou-domain protein binding sites results in reduced expression throughout the
      neural tube while mutation of the Pbx/Hox binding site results in loss of
      expression in the anterior domain in which Hox family members from paralogous
      groups 1-5 are expressed. These observations demonstrate that binding elements
      for both neural and anterior-posterior position specific transcription factors
      mediate domains of Pax3 expression.

PMID- 15465490
TI  - Expression of Fibroblast growth factor 19 (Fgf19) during chicken embryogenesis
      and eye development, compared with Fgf15 expression in the mouse.
AB  - The normal development of eyes relies on proper signaling through Fibroblast
      growth factor (FGF) receptors, but the source and identity of cognate ligands
      have remained largely unknown. We have found that Fgf19 is expressed in the
      developing chicken retina. In situ hybridization discloses dynamic expression
      patterns for Fgf19 in the optic vesicle, lens primordia and retinal horizontal
      cells. Overall expression pattern of Fgf19 during chicken embryogenesis was also
      examined: Fgf19 is expressed in the regions associated with cranial placodes
      induction, boundary regions of rhombomeres, somites, specific groups of neural
      cells in midbrain, hindbrain, and those derived from epibranchial placodes, and
      the apical ectodermal ridge of limb buds. Expression pattern of the Fgf19
      orthologous gene Fgf15 was further examined in the mouse developing eye. Fgf15 is
      expressed in the optic vesicle, a subset of progenitor cells of neural retina,
      and emerging ganglion and amacrine cells during retinogenesis.

PMID- 15465491
TI  - Identification of distinct genes with restricted expression in the somitic
      mesoderm in Xenopus embryo.
AB  - We have used whole-mount in situ hybridisation to identify genes expressed in the
      somitic mesoderm during Xenopus early development. We report here the analysis of
      eight genes whose expression pattern has not been described previously. They
      include the Xenopus homologues of eukaryotic initiation factor 2beta, methionine
      adenosyltransferase II, serine dehydratase, alpha-adducin, oxoglutarate
      dehydrogenase, fragile X mental retardation syndrome related protein 1,
      monocarboxylate transporter and voltage-dependent anion channel 1. Interestingly,
      these genes exhibit very dynamic expression pattern during early development. At
      early gastrula stages several genes do not show localised expression pattern,
      while other genes are expressed in the marginal mesoderm or in ectoderm. As
      development proceeds, the expression of these genes is gradually restricted to
      different compartments of somite. This study thus reveals an unexpected dynamic
      expression pattern for various genes with distinct function in vertebrates.

PMID- 15465492
TI  - Expression of the tudor-related gene Tdrd5 during development of the male
      germline in mice.
AB  - Homologues of Drosophila germ cell determinant genes such as vasa, nanos and
      tudor have recently been implicated in development of the male germline in mice.
      In the present study, the mouse gene encoding Tudor domain containing protein 5
      (TDRD5) was isolated from a 12.5-13.5 days post coitum (dpc) male-enriched
      subtracted cDNA library. Whole-mount in situ hybridization analysis of Tdrd5
      expression in the mouse embryonic gonad indicated that this gene is upregulated
      in the developing testis from 12.5 dpc, with expression levels remaining higher
      in testis than ovary throughout embryogenesis. Expression of Tdrd5 was absent in
      testes isolated from We/We embryos, which lack germ cells. In situ hybridization
      (ISH) on cryosectioned 13.5 dpc testes suggests that expression of Tdrd5, like
      that of Oct4, is restricted to germ cells. Northern hybridization analysis of
      expression in adult tissues indicated that Tdrd5 is expressed in the testis only,
      implying that expression of this gene is restricted to the male germline
      throughout development to adulthood.

PMID- 15465493
TI  - Expression of Hairy/Enhancer of Split genes, Hes1 and Hes5, during murine nephron
      morphogenesis.
AB  - Hairy/Enhancer of Split (Hes) genes encode transcriptional repressors that
      function as downstream targets of activated Notch receptors in cell fate
      decisions during tissue development. During nephrogenesis, multiple Notch pathway
      genes are co-expressed in multi-potent epithelial progenitors (i.e. pre-tubular
      aggregates), but demonstrate distinct expression patterns in early nephrons (i.e.
      S-shaped bodies), suggesting that Notch signaling functions in patterning
      epithelial cell fate during nephron morphogenesis. To define the spatial
      activation of the Notch pathway in developing nephrons, we analyzed the
      expression of Hes1 and Hes5 by mRNA in situ hybridization in cryosections of
      developing kidneys, and compared their spatiotemporal expression with the
      expression of other Notch pathway genes in nephron progenitors. Hes1, and to a
      lesser extent Hes5, were expressed in pre-tubular aggregates and comma-shaped
      bodies of embryonic day (E) 13.5 and newborn kidneys. In S-shaped bodies, Hes1
      expression was detected in the middle part which gives rise to the proximal
      tubule, but also extended into the lower and upper parts which give rise to the
      glomerulus and distal tubule, respectively, and was similar to the proximal
      distal expression patterns for Notch1 and Jagged1 in these nephrogenic
      structures. In contrast, strong Hes5 expression was restricted to the middle
      segment of S-shaped bodies, and resembled Delta-like 1 expression. These data
      show that Hes1 and Hes5 expression are independently regulated along the proximal
      distal axis of the developing nephron. Consequently, the differential, spatial
      regulation of Hes1 and Hes5 gene expression by the Notch signaling pathway in
      developing nephrons may be a mechanism for patterning cell fate decisions during
      nephron morphogenesis.

PMID- 15465494
TI  - Developmental expression of the Notch signaling pathway genes during mouse
      preimplantation development.
AB  - Notch signaling is an evolutionary conserved pathway involved in intercellular
      signaling and essential for proper cell fate choices during development. Thus, it
      could be involved in mouse preimplantation development where intercellular
      signaling plays a crucial role, particularly between the inner cell mass and the
      trophectoderm of the blastocyst. At their face value, the phenotypes observed
      when disrupting each of the four Notch genes known in the mouse do not support
      this view as none of them involves perturbation of preimplantation development.
      However this could be due to functional redundancy and/or maternal expression. As
      a first step to address this issue, we decided to examine the expression in early
      development of various genes known to participate in Notch signaling. Here, we
      report on the expression pattern of Notch1-4, Jagged1 (Jag1), Jag2, Delta-like1
      (Dll-1), Dll-3, Dll-4, Rbpsuh, Deltex1(Dtx1)and Dtx2 genes during preimplantation
      development from unfertilized eggs until late blastocyst stage using a RT-PCR
      strategy. We show that Notch1, 2, Jag1-2, Dll-3, Rbpsuh and Dtx2 transcripts are
      expressed at all stages. Notch4 and Dll-4 mRNAs are synthesized from the 2-cell
      through to the hatched blastocyst stage. Notch3, Dll-1 and Dtx1exhibit a stage
      dependent expression as their mRNAs are detected in 2-cell embryos and in hatched
      blastocysts, but are absent or weakly detected at the morula stage. Finally, we
      show that all the above genes are expressed both in Embryonic and Trophoblast
      Stem cells (ES and TS cells, respectively). Our results suggest that the Notch
      pathway may be active during mouse preimplantation development.

PMID- 15465495
TI  - Cloning and expression of an SH3 domain-containing protein (Xchef-1), a novel
      downstream target of activin/nodal signaling.
AB  - The activity of the activin/nodal signaling cascade is essential for the proper
      specification of germ layers during gastrulation. Many of the components of this
      signaling pathway have been identified, but relatively few downstream targets
      have been discovered. Using cDNA microarrays, we have identified a novel SH3
      domain-containing gene we have named Xchef-1 that is upregulated in response to
      activin/nodal signaling. Xchef-1 is a direct downstream target of activin and is
      expressed in the marginal zones of gastrulating Xenopus embryos in a dynamic
      pattern reminiscent of nodal expression. At neurula stages, Xchef-1 is expressed
      in neural crest of the head and trunk as well as in the anterior neural plate.
      These domains of expression are then restricted at tailbud stages to the
      branchial arches, and the region of the future gall bladder.

PMID- 15465496
TI  - Expression patterns of dachshund during head development of Gryllus bimaculatus
      (cricket).
AB  - We report that Gryllus bimaculatus dachshund (Gbdac), a cricket homologue of
      Drosophila dachshund (Dmdac), is expressed in the developing eye and brain.
      During brain development, Gbdac was first expressed in the medial head region,
      corresponding to a part of developing protocephalic region, and expressed in the
      primordial and adult Kenyon cells. During eye development, Gbdac was first
      expressed in the lateral head region, becoming to the eye primordium and a part
      of the deutocerebrum. Then, Gbdac was expressed in the posterior region of the
      eye primordium, prior to the formation of compound eyes. The expression domain
      shifted to the anterior domain concomitantly with the movement of morphogenetic
      furrows. Gbdac was also expressed in the developing optic lobes during
      differentiation of the retina. These expression patterns were compared with those
      of Dmdac. We found that although developmental processes of the Gryllus eye and
      brain differ from those of the Drosophila ones, the expression patterns of Gbdac
      are essentially similar to those of the Dmdac.

PMID- 15465498
TI  - Expression patterns of the novel imprinted genes Nap1l5 and Peg13 and their non
      imprinted host genes in the adult mouse brain.
AB  - Recent work has implicated imprinted gene functioning in neurodevelopment and
      behaviour and defining the expression patterns of these genes in brain tissue has
      become a key prerequisite to establishing function. In this work we report on the
      expression patterns of two novel imprinted loci, Nap1l5 and Peg13, in adult mouse
      brain using in situ hybridisation methods. Nap1l5 and Peg13 are located,
      respectively, within the introns of the non-imprinted genes Herc3 and the
      Tularik1 (T1)/KIAA1882 homologue in two separate microimprinted domains on mouse
      chromosomes 6 and 15. These 'host' genes are highly expressed in brain and
      consequently we were interested in assessing their expression patterns in
      parallel to the imprinted genes. The brain expression of all four genes appeared
      to be mainly neuronal. The detailed expression profiles of Nap1l5 and Peg13 were
      generally similar with widespread expression that was relatively high in the
      septal and hypothalamic regions, the hippocampus and the cerebral cortex. In
      contrast, there was some degree of dissociation between the imprinted genes and
      their non-imprinted hosts, in that, whilst there was again widespread expression
      of Herc3 and the T1/KIAA1882 homologue, these genes were also particularly highly
      expressed in Purkinje neurons and piriform cortex. We also examined expression of
      the novel imprinted genes in the adrenal glands. Nap1l5 expression was localised
      mainly to the adrenal medulla, whilst Peg13 expression was observed more
      generally throughout the adrenal medulla and the outer cortical layers.

PMID- 15465497
TI  - CTIP1 and CTIP2 are differentially expressed during mouse embryogenesis.
AB  - Chicken ovalbumin upstream promoter transcription factor-interacting proteins 1
      and 2 (CTIP1 and CTIP2) are related transcriptional regulatory proteins. While
      overexpression of both of these proteins has been linked to the development of
      several lymphoid malignancies, lack of CTIP1 and CTIP2 expression results in
      defective lymphopoiesis and abnormal thymocyte development, respectively. Here,
      we describe the expression patterns of CTIP1 and CTIP2 during mouse embryogenesis
      and in the post-natal brain. Both CTIP1 and CTIP2 were expressed diffusely in the
      embryo at 10.5 days post-coitum (d.p.c.). However, the expression of both genes
      became increasingly restricted to the central nervous system (CNS) during the
      course of fetal development, culminating with high, but differential, expression
      levels throughout the hippocampal subregions, olfactory bulb and cortex, limbic
      system, basal ganglia and frontal cortex of the developing brain, and in dorsal
      cells of the spinal cord. The brain expression domains of CTIP1 and CTIP2 were
      maintained into adulthood. Outside the CNS, both genes exhibited differential
      expression within the facial mesenchyme at 12.5 d.p.c., and CTIP2 was selectively
      expressed from day 12.5 onwards in the olfactory epithelium and developing
      thymus, and to a lesser extent in oral and gut epithelia. Strong CTIP2 expression
      was maintained in the thymus at 18.5 d.p.c. These results support the selective
      contributions of both CTIP1 and CTIP2 in the development and function of both the
      central nervous and immune systems and the importance of future investigations to
      define the function(s) of both proteins.

PMID- 15465499
TI  - Ezrin gene, coding for a membrane-cytoskeleton linker protein, is regionally
      expressed in the developing mouse neuroepithelium.
AB  - Ezrin is a member of the Ezrin, Radixin, Moesin (ERM) proteins family that are
      proposed to act as linkers between the cytoskeleton and plasma membrane. Ezrin
      regulates cell-cell and cell-matrix interactions playing a role in the regulation
      of cellular adhesion, movement and morphology in epithelia. Alterations in the
      expression of Ezrin and other members of ERM family have also been observed in
      brain tumours. Here we report the expression pattern of Ezrin during mouse neural
      development, from early stages to postnatal stages. In young and middle gestation
      embryos, Ezrin is expressed in the roof plate of the neural tube, in the
      presumptive domain of the choroidal plexus, and in some precise domains of
      ventricular epithelium. These domains are distributed in basal and alar
      neuroepithelial regions, some of them in relation to the expression of cadherins.
      At later gestation and postnatal stages, Ezrin expression is maintained on the
      mature choroidal plexus and is weakly detected in the proliferative regions of
      the mature brain.

PMID- 15465500
TI  - Drapc1 expression during mouse embryonic development.
AB  - We identified the mouse homolog of human DRAPC1 (APCDD1) gene, shown to be a
      target of Wnt/beta-catenin signaling pathway in cancer cell lines. Analysis of
      its spatiotemporal expression in mouse embryos from E7.5 to E14 showed that
      Drapc1 is expressed during development of the extraembryonic structures, nervous
      system, vascular system and inner ear. In addition, Drapc1 is expressed in the
      mesenchyme of several developing organs at sites of epithelio-mesenchymal
      interactions. Drapc1 expression was also found in the hair follicles of the adult
      mouse skin. Similarity of Drapc1 expression pattern to location of active beta
      catenin in developing mouse embryo further suggests that mouse Drapc1 is a novel
      in vivo target gene of Wnt/beta-catenin signaling pathway.

PMID- 15465501
TI  - Effects of tai chi mind-body movement therapy on functional status and exercise
      capacity in patients with chronic heart failure: a randomized controlled trial.
AB  - PURPOSE: To examine the effects of a 12-week tai chi program on quality of life
      and exercise capacity in patients with heart failure. METHODS: Thirty patients
      with chronic stable heart failure and left ventricular ejection fraction < or
      =40% (mean [+/- SD] age, 64 +/- 13 years; mean baseline ejection fraction, 23% +/
      7%; median New York Heart Association class, 2 [range, 1 to 4]) were randomly
      assigned to receive usual care (n = 15), which included pharmacologic therapy and
      dietary and exercise counseling, or 12 weeks of tai chi training (n = 15) in
      addition to usual care. Tai chi training consisted of a 1-hour class held twice
      weekly. Primary outcomes included quality of life and exercise capacity.
      Secondary outcomes included serum B-type natriuretic peptide and plasma
      catecholamine levels. For 3 control patients with missing data items at 12 weeks,
      previous values were carried forward. RESULTS: At 12 weeks, patients in the tai
      chi group showed improved quality-of-life scores (mean between-group difference
      in change, -25 points, P = 0.001), increased distance walked in 6 minutes (135
      meters, P = 0.001), and decreased serum B-type natriuretic peptide levels (-138
      pg/mL, P = 0.03) compared with patients in the control group. A trend towards
      improvement was seen in peak oxygen uptake. No differences were detected in
      catecholamine levels. CONCLUSION: Tai chi may be a beneficial adjunctive
      treatment that enhances quality of life and functional capacity in patients with
      chronic heart failure who are already receiving standard medical therapy.

PMID- 15465502
TI  - Comparative efficacy of hormone replacement therapy, etidronate, calcitonin,
      alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: The
      Yamaguchi Osteoporosis Prevention Study.
AB  - PURPOSE: To assess the comparative effectiveness of several medications on bone
      mineral density, biochemical bone markers, and the incidence of vertebral
      fractures in postmenopausal women with osteoporosis. METHODS: A total of 396
      postmenopausal women, aged 50 to 75 years, were allocated randomly to six equal
      sized groups: hormone replacement therapy, etidronate, eel calcitonin,
      alfacalcidol, vitamin K (menatetrenone), or control (no treatment). Thoracic and
      lumbar spine radiographs, bone mineral density at the distal radius, and markers
      of bone turnover were assessed at baseline and every 3 months during the 2-year
      study. RESULTS: Compared with baseline, the 2-year mean changes in bone mineral
      density were 2.0% for hormone replacement therapy, -0.5% for etidronate, 1.6% for
      calcitonin, -3.6% for alfacalcidol, -1.9% for vitamin K, and -3.3% for control.
      Seventeen (26%) of the 66 control patients developed new vertebral fractures.
      Compared with controls, the relative risks of vertebral fracture were 0.35 (95%
      confidence interval [CI]: 0.14 to 0.83) for hormone replacement therapy, 0.40
      (95% CI: 0.17 to 0.92) for etidronate, 0.41 (95% CI: 0.17 to 0.93) for
      calcitonin, 0.56 (95% CI: 0.26 to 1.12) for alfacalcidol, and 0.44 (95% CI: 0.20
      to 0.99) for vitamin K. CONCLUSION: We observed significant reductions in the
      incidence of vertebral fractures with hormone replacement therapy, etidronate,
      and calcitonin, and significant improvements in bone mineral density with hormone
      replacement therapy and calcitonin.

PMID- 15465503
TI  - Synovial fluid leukocyte count and differential for the diagnosis of prosthetic
      knee infection.
AB  - PURPOSE: Criteria for the interpretation of synovial fluid are well established
      for native joint disorders but lacking for the evaluation of prosthetic joint
      failure. Our aim was to define cutoff values for synovial fluid leukocyte count
      and neutrophil percentage for differentiating aseptic failure and prosthetic
      joint infection. METHODS: We performed a prospective study of 133 patients in
      whom synovial fluid specimens were collected before total knee arthroplasty
      revision between January 1998 and December 2003. Patients with underlying
      inflammatory joint disease were excluded. RESULTS: Aseptic failure was diagnosed
      in 99 patients and prosthetic joint infection was diagnosed in 34 patients. The
      synovial fluid leukocyte count was significantly higher in patients with
      prosthetic joint infection (median, 18.9 x 10(3)/microL; range, 0.3 to 178 x
      10(3)/microL) than in those with aseptic failure (median, 0.3 x 10(3)/microL;
      range, 0.1 to 16 x 10(3)/microL; P <0.0001); the neutrophil percentage was also
      significantly higher in patients with prosthetic joint infection (median [range],
      92% [55% to 100%] vs. 7% [0% to 79%], P <0.0001). A leukocyte count of >1.7 x
      10(3)/microL had a sensitivity of 94% and a specificity of 88% for diagnosing
      prosthetic joint infection; a differential of >65% neutrophils had a sensitivity
      of 97% and a specificity of 98%. Staphylococcus aureus was the only pathogen
      associated with leukocyte counts >100 x 10(3)/microL. CONCLUSION: A synovial
      fluid leukocyte differential of >65% neutrophils (or a leukocyte count of >1.7 x
      10(3)/microL) is a sensitive and specific test for the diagnosis of prosthetic
      knee infection in patients without underlying inflammatory joint disease.

PMID- 15465504
TI  - Effects of a structured patient-centered discharge interview on patients'
      knowledge about their medications.
AB  - PURPOSE: Many recently hospitalized patients lack knowledge about important
      aspects of their medications. We evaluated whether a structured discharge
      interview could improve medication knowledge. METHODS: Patients discharged with
      at least one discharge medication were recruited from two general internal
      medicine services (one experimental and one control) of a teaching hospital.
      During a 3-month baseline period, usual care at discharge was provided in both
      services. During the ensuing 3-month period, observation was continued in the
      control service; residents in the experimental service implemented the
      intervention, which consisted of a structured patient-centered discharge
      interview during which a computer-generated individualized treatment card was
      discussed with and provided to patients. One week after discharge, patients'
      knowledge about their medications was assessed by telephone. RESULTS: We enrolled
      a total of 809 patients. After adjustment for patients' characteristics and for
      the effect of time, the intervention significantly increased the percentage of
      medications for which patients correctly knew the purposes (adjusted difference =
      6%; 95% confidence interval [CI]: 3% to 8%; P <0.001), possible side effects
      (adjusted difference = 19%; 95% CI: 9% to 29%; P <0.001), and precautions to
      observe (adjusted difference = 9%; 95% CI: 2% to 19%; P <0.001). However, the
      number of medications that patients discontinued after discharge was not
      modified. Patients with a better knowledge of side effects of their active
      treatment were less likely to discontinue their medications, but there were no
      associations with other types of knowledge. CONCLUSION: A structured patient
      centered discharge interview, performed by residents using a standardized
      treatment card, significantly increased patients' knowledge about their
      medications. Its effects on compliance require further study.

PMID- 15465505
TI  - Self-reported management of pain in hospitalized patients: link between process
      and outcome.
AB  - PURPOSE: Hospitalized patients commonly experience pain. We investigated the
      association between patients' reported use of recommended pain management
      practices and overall pain relief. METHODS: All adult patients discharged during
      a 1-month period from a Swiss teaching hospital were invited to complete a mailed
      survey that included the Picker patient experience questionnaire, questions on
      pain relief during hospitalization, and questions on various procedures that are
      recommended as standards of pain management. RESULTS: Of 2156 eligible patients,
      1518 (70%) participated. Sixty-nine percent (n = 1050) had experienced pain
      during their hospital stay, of whom 71% (n = 697/978) reported complete pain
      relief. After adjustment for sex, age, general health, and hospital department,
      pain relief was associated independently with availability of physicians (odds
      ratio [OR] = 11; 95% confidence interval [CI]: 3.3 to 36 for excellent vs. poor
      availability), having received information about pain and its management (OR =
      2.8; 95% CI: 1.8 to 4.2), regular pain assessment (OR = 1.8; 95% CI: 1.2 to 2.8),
      modification of pain treatment when ineffective (OR = 3.0; 95% CI: 1.6 to 5.6),
      and waiting less than 10 minutes for pain medications (OR = 3.5; 95% CI: 1.9 to
      6.6). CONCLUSION: Patient reports that recommended pain management procedures had
      been used were associated with better self-reported pain relief among
      hospitalized patients.

PMID- 15465506
TI  - Are patients more likely to see physicians of the same sex? Recent national
      trends in primary care medicine.
AB  - PURPOSE: Women may prefer female physicians, particularly for preventive health
      services. We assessed national trends in the proportion of women among patients
      seeing female physicians, and compared visit characteristics and preventive
      services among visits to female and male primary care physicians. METHODS: We
      assessed the characteristics of 92,389 visits from the 1995-2000 National
      Ambulatory Medical Care Survey, a nationally representative survey of office
      based physicians in the United States, using linear and logistic regression.
      RESULTS: Female physicians were more likely than male physicians to see female
      patients in the specialties of primary care (73% vs. 56%), psychiatry (72% vs.
      54%), dermatology (67% vs. 56%), and pediatrics (52% vs. 46%; P <0.01 for all).
      In primary care, the difference increased over time, such that by 2000, 78% of
      visits to female primary care physicians were from women, compared with 56% for
      male primary care physicians (P <0.01). Female primary care physicians saw
      younger patients (mean age, 45 vs. 49 years, P = 0.04), reported longer visits
      (19 vs. 17 minutes, P <0.01), and reported performing more preventive services
      than did male primary care physicians when seeing female patients, including
      Papanicolaou testing (11% vs. 4.7%, P <0.01) and mammograms (9% vs. 4%, P <0.01).
      CONCLUSION: The phenomenon of sex concordance between patient and physician has
      increased in recent years, particularly in primary care. Nearly four of five
      patient visits to female primary care physicians are from women, and female
      physicians report performing more preventive health services for their female
      patients.

PMID- 15465507
TI  - Availability of large-scale evidence on specific harms from systematic reviews of
      randomized trials.
AB  - PURPOSE: To assess how frequently systematic reviews of randomized controlled
      trials convey large-scale evidence on specific, well-defined adverse events.
      METHODS: We searched the Cochrane Database of Systematic Reviews for reviews
      containing quantitative data on specific, well-defined harms for at least 4000
      randomized subjects, the minimum sample required for adequate power to detect an
      adverse event due to an intervention in 1% of subjects. Main outcome measures
      included the number of reviews with eligible large-scale data on adverse events,
      the number of ineligible reviews, and the magnitude of recorded harms (absolute
      risk, relative risk) based on large-scale evidence. RESULTS: Of 1727 reviews, 138
      included evidence on > or =4000 subjects. Only 25 (18%) had eligible data on
      adverse events, while 77 had no harms data, and 36 had data on harms that were
      nonspecific or pertained to <4000 subjects. Of 66 specific adverse events for
      which there were adequate data in the 25 eligible reviews, 25 showed
      statistically significant differences between comparison arms; most pertained to
      serious or severe adverse events and absolute risk differences <4%. In 29% (9/31)
      of a sample of large trials in reviews with poor reporting of harms, specific
      harms were presented adequately in the trial reports but were not included in the
      systematic reviews. CONCLUSION: Systematic reviews can convey useful large-scale
      information on adverse events. Acknowledging the importance and difficulties of
      studying harms, reporting of adverse effects must be improved in both randomized
      trials and systematic reviews.

PMID- 15465508
TI  - Adult phenylketonuria.
AB  - Newborn screening for phenylketonuria began 35 to 40 years ago in most
      industrialized countries. Because of this initiative, which resulted in early
      institution of phenylalanine-restricted diets, there are now many young adults
      with this disease who have normal or near-normal intellectual function. In North
      America alone, 200 patients with phenylketonuria enter adulthood every year. Most
      expert panels recommend following a phenylalanine-restricted "diet for life."
      However, there are few adult physicians dedicated to continuing care of this
      group, with the possible exception of maternal phenylketonuria. Up to 10% of
      adults with classic phenylketonuria, and possibly 50% of those with milder
      variants, may not need treatment; after adolescence, intelligence does not appear
      to deteriorate, at least into early adulthood, even if diet therapy is
      discontinued or not in good control. However, neuropsychological and psychosocial
      problems develop frequently, needing focused and intensive support by health care
      providers. New investigative methods and treatment options are on the horizon.
      There is an urgent need for physicians who will orchestrate the care of adults
      with phenylketonuria.

PMID- 15465509
TI  - Effects of statins on stroke prevention in patients with and without coronary
      heart disease: a meta-analysis of randomized controlled trials.
AB  - PURPOSE: To assess if lipid-lowering interventions (statins, fibrates, resins, n
      3 fatty acids, diet) prevent nonfatal and fatal strokes in patients with and
      without coronary heart disease. METHODS: We systematically searched the
      literature up to August 2002 to retrieve all randomized controlled trials of
      lipid-lowering interventions that reported nonfatal and fatal stroke and
      mortality data. The search yielded 65 trials with 200,607 patients for a meta
      analysis to determine whether treatment effects differed between types of lipid
      lowering interventions and between patient samples with and without coronary
      heart disease. RESULTS: The risk ratio for nonfatal and fatal stroke for statins
      as compared with control interventions was 0.82 (95% confidence interval [CI]:
      0.76 to 0.90). The corresponding risk ratios for statins as compared with control
      were 0.75 (95% CI: 0.65 to 0.87) for patients with coronary heart disease and
      0.77 (95% CI: 0.62 to 0.95) for those without coronary heart disease. The
      confidence intervals of risk ratios for nonfatal and fatal stroke associated with
      fibrates, resins, n-3 fatty acids, and diet all included 1, as did the confidence
      intervals for these interventions in patients with and without coronary heart
      disease. Weighted meta-regression analysis suggested a stronger association of
      stroke reduction with statin treatment than with the extent of cholesterol
      reduction. CONCLUSION: This meta-analysis suggests that statins reduce the
      incidence of stroke in patients with and without coronary heart disease.

PMID- 15465510
TI  - Risk factors for renal failure among 72 consecutive patients with rhabdomyolysis
      related to illicit drug use.

PMID- 15465511
TI  - Benefits of tai chi in chronic heart failure: body or mind?

PMID- 15465512
TI  - The new faces of primary care.

PMID- 15465513
TI  - The last day of the past is the first day of the future: Transitional care for
      genetic patients.

PMID- 15465515
TI  - Cost-effectiveness of inhaled corticosteroids in chronic obstructive pulmonary
      disease.

PMID- 15465516
TI  - Pure red cell aplasia following pegylated interferon alpha treatment.

PMID- 15465517
TI  - Spinal cord compression from intradural extramedullary tuberculoma.

PMID- 15465518
TI  - The lack of diagnostic value of the indium scan in acute bacterial endocarditis.

PMID- 15465519
TI  - Transient cardiac dysfunction in acute carbon monoxide poisoning.

PMID- 15465520
TI  - 25-year follow-up of a case of giant cell aortitis.

PMID- 15465522
TI  - Neural responses to territorial challenge and nonsocial stress in male song
      sparrows: segregation, integration, and modulation by a vasopressin V1
      antagonist.
AB  - The present experiments were conducted to determine (1) which basal forebrain
      regions and/or their peptidergic components are responsive to social challenge
      and nonsocial stress, and (2) the influence of an arginine vasopressin V(1)
      antagonist (AVPa) on these responses. Experiments were conducted in wild-caught
      male song sparrows (Melospiza melodia) that were housed on seminatural
      territories (field-based flight cages). Subjects were each fitted with a chronic
      guide cannula directed at the lateral ventricle and exposed to one of five
      conditions before sacrifice and histochemistry: saline + simulated territorial
      intrusion (STI; consisting of song playback and presentation of a caged
      conspecific male), AVPa + STI, saline + empty cage, AVPa + empty cage, unhandled.
      Two tissue series were prepared and immunofluorescently double-labeled for ZENK
      (egr-1) protein and either arginine vasotocin (AVT; avian homologue of AVP) or
      corticotropin releasing factor (CRF). The results indicate that the neuronal
      populations that are sensitive to nonsocial stress (capture, handling and
      infusion) and STI are at least partially segregated. Increases in ZENK
      immunoreactive (-ir) nuclei following handling and infusion were observed in a
      large number of areas, whereas neural responses that were specific to STI were
      more limited. However, multiple areas showed responses to both handling and STI.
      AVPa infusions significantly reduced or eliminated most experimental increases in
      ZENK-ir, suggesting a broad role for endogenous AVT in the modulation of baseline
      activity and/or stress responsivity, and a much more limited role in the specific
      response to social challenge. Particular attention is given to the numerous zones
      of the lateral septum (LS), which are differentially responsive to handling, STI,
      and V(1)-like receptor blockade. These data suggest that septal AVT modulates
      neural responses to general stressors, not social stimuli specifically. Thus,
      species differences in septal AVT function (as previously described in songbirds)
      likely reflect differences in the relationship of stress or anxiety to species
      specific behaviors, or to behavior in species-typical contexts.

PMID- 15465523
TI  - Hormonal correlates for the initiation of breast-feeding in Bangladeshi women.
AB  - Hormonal changes that occur before or during parturition are known to trigger
      early postpartum maternal behaviors in many mammals. In humans, little evidence
      has been found for hormonal mediation of early postpartum maternal behavior. In
      this paper, we investigate associations between fetoplacental hormone
      concentrations in late pregnancy on the time from parturition to initiation of
      breast-feeding. A sample of 91 pregnant rural Bangladeshi women, enrolled in a 9
      month prospective study, provided twice-weekly urine specimens and structured
      interviews. The subjects provided self-reports of time from parturition to
      initiation of breast-feeding. Specimens were assayed for urinary concentrations
      of human chorionic gonadotropin (hCG), pregnanediol-3alpha-glucuronide (PdG, a
      metabolite of progesterone), and urinary estrone conjugates (E1C). Parametric
      hazards analysis was used to investigate the effects of hCG, PdG, and E1C
      concentrations and other covariates (mother's age, parity, and child's sex) on
      the duration from parturition to breast-feeding. Mother's age, parity, the
      child's sex, hCG, and PdG showed no association with the onset of breast-feeding.
      Urinary E1C was significantly associated with time to initiation of breast
      feeding, explaining about 4% of the variation in the behavior. The relationship
      was positive so that higher prepartum concentrations of EIC were associated with
      later times to initiation of breast-feeding. The direction of this relationship
      is opposite that found for many other species of mammals but is consistent with
      some recent findings in primates.

PMID- 15465524
TI  - Fecal androgens of bison bulls during the rut.
AB  - The influence of sex hormones is a key proximate factor underlying male
      reproductive behavior in mammals. Effective conservation policies for the
      remaining purebred plains bison (Bison bison bison) herds require knowledge of
      the physiology underlying bison reproductive biology. We used fecal steroid
      analysis to characterize androgen levels in adult bison bulls before, during, and
      after the rut, and to examine androgen levels of bulls differing in reproductive
      status, age, and mating success. Fieldwork was carried out at the Fort Niobrara
      National Wildlife Refuge in north-central Nebraska. All adult bison in the herd
      were individually known by unique brands. Fecal samples were collected during
      2003 from bulls during pre-rut (June), rut (July-August), and post-rut
      (September), and behavioral observations focused on reproductive status and
      mating success during the rut. Matched sample data indicated that androgen levels
      (ng/g feces) of bulls peaked during the rut, doubling from pre-rut to rut and
      then declining by 75% during post-rut. Dominant bulls that tended (guarded) cows
      maintained higher androgen levels than bulls that were not tending. There was a
      positive correlation between bull age (associated with mating success) and
      androgens, with higher androgen levels in prime-aged bulls compared with younger
      bulls. Nonetheless, there was no correlation between mating success (measured by
      number of copulations observed) and androgen level. This suggests that while
      androgens may provide the proximate motivation to compete for matings, other
      factors determine the mating success of bison bulls.

PMID- 15465525
TI  - Ontogeny of corticotropin-releasing factor effects on locomotion and foraging in
      the Western spadefoot toad (Spea hammondii).
AB  - We investigated the effects of corticotropin-releasing factor (CRF) and
      corticosterone (CORT) on foraging and locomotion in Western spadefoot toad (Spea
      hammondii) tadpoles and juveniles to assess the behavioral functions of these
      hormones throughout development. We administered intracerebroventricular
      injections of ovine CRF or CRF receptor antagonist alphahelical CRF((9-41)) to
      tadpoles and juveniles, and observed behavior within 1.5 h after injection. In
      both premetamorphic (Gosner stage 33) and prometamorphic (Gosner stages 35-37)
      tadpoles, CRF injections increased locomotion and decreased foraging. Injections
      of alphahelical CRF((9-41)) reduced locomotion but did not affect foraging in
      premetamorphic tadpoles, but dramatically increased foraging in prometamorphic
      tadpoles compared to both placebo and uninjected controls. Similarly,
      alphahelical CRF((9-41)) injections stimulated food intake and prey-catching
      behavior in juveniles. These results suggest that in later-staged amphibians,
      endogenous CRF secretion modulates feeding by exerting a suppressive effect on
      appetite. By contrast to the inhibitory effect of CRF, 3-h exposure to CORT (500
      nM added to the aquarium water) stimulated foraging in prometamorphic tadpoles.
      These tadpoles also exhibited a CORT-mediated increase in foraging 6 h after CRF
      injection, which was associated with elevated whole-body CORT content and blocked
      by glucocorticoid receptor (GR) antagonist (RU486) injections. Thus, exogenous
      CRF influences locomotion and foraging in both pre- and prometamorphic tadpoles,
      but endogenous CRF secretion in relatively unstressed animals does not affect
      foraging until prometamorphic stages. Furthermore, the opposing actions of CRF
      and CORT on foraging suggest that they are important regulators of energy balance
      and food intake in amphibians throughout development.

PMID- 15465526
TI  - The effects of adrenalectomy and corticosterone replacement on maternal behavior
      in the postpartum rat.
AB  - It is well known that the hypothalamic-pituitary-adrenal (HPA) axis is activated
      during stress. Recent work suggests it is also implicated in the regulation of
      "normal" behaviors. The present studies investigated the effects of adrenalectomy
      and of varying glucocorticoid concentrations on adult maternal behavior in
      primiparous rats. In two studies, rats in late pregnancy were adrenalectomized or
      given sham surgeries and were tested for maternal behavior. In the first study,
      primiparous rats were given 0, 25, 100, 300, or 500 microg/ml of corticosterone
      in their drinking water. In the second study, primiparous rats were given either
      control or corticosterone time-release pellets. Blood samples were taken to
      ensure that rats demonstrated levels of corticosterone in blood that were
      relative to doses received. In studies one and two, primiparous adrenalectomized
      rats showed slightly, but significantly, lower levels of some maternal behaviors,
      including licking and time in nest, than primiparous sham rats. Primiparous rats
      given higher doses of corticosterone replacement showed higher levels of these
      maternal behaviors than primiparous rats given lower doses of corticosterone. In
      conclusion, adrenalectomy decreases, but does not abolish, maternal behavior.
      Corticosterone replacement reverses these effects. Corticosterone is not
      necessary for the initiation or maintenance of maternal behavior but plays a role
      in the modulation of ongoing maternal behavior.

PMID- 15465527
TI  - The Nhlh2 transcription factor is required for female sexual behavior and
      reproductive longevity.
AB  - Nhlh2 is a member of the basic helix-loop-helix (bHLH) transcription factor
      family and is expressed in developing and adult neuroendocrine tissues such as
      the pituitary and hypothalamus. Targeted deletion of Nhlh2 (N2KO) in mice results
      in hypogonadism and obesity. While gonadally intact male N2KO mice are infertile
      and lack male sexual behavior, female N2KO mice can become pregnant and carry
      litters to full term. Unlike normal females in which fertility averages 8-12
      months with approximately one pregnancy per month, N2KO females have a shorter
      reproductive span with most females supporting only three to four pregnancies in
      a 9-month period. In addition, N2KO females exhibit abnormal estrous cycles
      characterized by a truncated estrus and a prolonged proestrus. We have found that
      while young female N2KO mice ovulate the same number of oocytes as normal females
      in response to exogenous hormones, the number of oocytes released by aged N2KO
      females is reduced over 50%. Interestingly, oocytes from N2KO females are equally
      competent for in vitro fertilization assays when compared to oocytes from
      similarly aged normal and heterozygous mice. We have further demonstrated that
      both young and old N2KO females show at least a 50% reduction in hormone
      stimulated sexual behavior as measured by their lordosis quotient. This suggests
      that N2KO females show a lifelong behavioral hyporesponsiveness to exogenous
      steroid hormones accompanied by a reduction in reproductive longevity via reduced
      ovulation with aging. Potential gene regulatory mechanisms that involve the
      action of the Nhlh2 transcription factor on female fertility and sexual behavior
      are discussed.

PMID- 15465528
TI  - Aggressive behavior in female golden hamsters: development and the effect of
      repeated social stress.
AB  - In male golden hamsters, agonistic behavior matures during puberty, changing from
      play fighting to adult-like aggression. In addition, this transition is
      accelerated by repeated social subjugation early in puberty. However, little is
      known about the development of agonistic behavior in females. In the present
      study, we compared the development of agonistic behavior in male and female
      golden hamsters. Furthermore, we also tested the effects of repeated social
      subjugation on the development of agonistic behavior during puberty. Hamsters
      were tested for agonistic behavior in the presence of a smaller intruder at
      different intervals during puberty. Several observations were made. First, the
      frequency of attacks remained stable in females, while varying in males. Second,
      the transition from play fighting to adult-like aggression occurred at earlier
      time periods in females than in males. Finally, a clear transitional period
      marked by attacks focused on the flanks was observable in males around mid
      puberty. However, this transitional period was not apparent in females. In
      addition, juvenile females were exposed to aggressive adult males or females. In
      both cases, repeated exposure to stress had no statistically significant effect
      on the development of agonistic behavior. After 2 weeks of subjugation, exposure
      to aggressive adults had no effect on serum cortisol levels, indicating that
      juvenile females habituate to repeated social stress. These data show significant
      sex differences in the development of agonistic behavior and adaptation to
      repeated stress in juvenile golden hamsters.

PMID- 15465529
TI  - Peripherally administered growth hormone increases brain dopaminergic activity
      and swimming in rainbow trout.
AB  - There is increasing evidence that growth hormone (GH) has important behavioral
      effects in fish, but the underlying mechanisms are not well understood. To
      investigate if peripherally administered GH influences the monoaminergic activity
      of the brain, and how this is correlated to behavior, juvenile rainbow trout were
      implanted intraperitoneally with ovine GH. Fish were either kept isolated or in
      groups of five. The physical activity and food intake of the isolated fish were
      observed after 1 and 7 days, when brains were also sampled. The content of
      serotonin, dopamine, and noradrenaline and their metabolites in hypothalamus,
      telencephalon, optic tectum, and brain stem was then analyzed. For fish kept
      isolated for 7 days following implant, GH increased swimming activity and the
      levels of the dopamine metabolite 3, 4-hydroxy-phenylacetic acid (DOPAC) were
      higher in all brain parts examined. In the optic tectum, the levels of the
      dopamine metabolite homovanillic acid (HVA) were lowered by the GH treatment. One
      day GH implant did not affect behavior or monoamine levels of isolated fish. In
      the fish kept in groups, a 7-day GH implant increased the hypothalamic levels of
      DOPAC, but not in the other brain parts examined, which may indicate an effect on
      the brain dopaminergic system from social interactions. It can be concluded that
      peripherally administered GH may function as a neuromodulator, affecting the
      dopaminergic activity of the rainbow trout brain, and this is associated with
      increased swimming activity.

PMID- 15465530
TI  - Effect of photoperiod on vasopressin-induced aggression in Syrian hamsters.
AB  - Syrian hamsters are photoperiodic and become sexually quiescent when exposed to
      short "winter-like" photoperiods. In short photoperiods, male hamsters display
      significantly higher levels of aggression than males housed in long photoperiods.
      Arginine-vasopressin (AVP) within the anterior hypothalamus (AH) has been
      reported to modulate aggression in hamsters housed in long photoperiods. Previous
      studies have shown that AVP can facilitate aggression and its effects appear to
      be mediated by AVP V(1a) receptors (V(1a)R). In the present study, we
      investigated whether the increased levels of aggression observed after exposure
      to short photoperiod were the result of an increased responsiveness to AVP within
      the AH. Injections of AVP into the AH significantly increased aggression in
      hamsters housed in a long photoperiod, but had no effect in hamsters housed in a
      short photoperiod. In addition, injection of a V(1a)R antagonist into the AH
      significantly inhibited aggression in hamsters housed in long photoperiod, but
      had no effect in hamsters housed in a short photoperiod. These findings indicate
      that AVP within the AH increases aggression in hamsters housed in long
      photoperiods, but not in hamsters housed in short photoperiods.

PMID- 15465531
TI  - Extinction of a conditioned response in rainbow trout selected for high or low
      responsiveness to stress.
AB  - Two lines of rainbow trout (Oncorhynchus mykiss) that exhibit divergent endocrine
      responsiveness to stressors also display disparate behavioral traits. To
      investigate whether the high-responding (HR) and low-responding (LR) fish also
      differ in cognitive function, the rate of extinction of a conditioned response
      was compared between the two lines. Groups of HR and LR fish were exposed to a
      paired conditioned stimulus (CS; water off) and unconditioned stimulus (US;
      confinement stressor). After exposure to 18 CS-US pairings, at least 70% of
      individuals of both lines acquired a conditioned response (CR) manifested as an
      elevation of blood cortisol levels on presentation of the CS only. Post
      conditioning, the fish were tested by presentation of the CS at weekly intervals,
      for 4 weeks, with no further reinforcement, and the extinction of the CR in the
      two lines was compared. The decline in mean plasma cortisol levels after exposure
      to the CS over successive tests suggested that the CR was retained for a shorter
      period among the HR (<14 days) than LR fish (<21 days). The frequency of
      individuals within each line whose plasma cortisol levels indicated a stress
      response when exposed to the CS was significantly greater among the LR than HR
      fish at 14 and 21 days with no HR fish falling into this category at 21 days. At
      28 days post-conditioning, there were no HR fish and only three LR fish were
      categorized as "stressed". These results suggest that there are differences in
      cognitive function between the two lines. Possible mechanisms underlying these
      differences are discussed.

PMID- 15465532
TI  - Stress during adolescence enhances locomotor sensitization to nicotine in
      adulthood in female, but not male, rats.
AB  - A wide body of research has indicated that perinatal exposure to stressors alters
      the organism, notably by programming behavioral and neuroendocrine responses and
      sensitivity to drugs of abuse in adulthood. Recent evidence suggests that
      adolescence also may represent a sensitive period of brain development, and yet
      there has been little research on the long-lasting effects of stressors during
      this period. We investigated the effects of pubertal social stress (PS; daily 1-h
      isolation followed by pairing with a new cage mate on postnatal days 33-48) on
      locomotor sensitization to injections of nicotine and corticosterone response to
      restraint stress when the rats were adults (approximately 3 weeks after PS).
      There were no differences among the groups in locomotor activity to injections of
      saline. However, PS females had enhanced locomotor sensitization to repeated
      doses of nicotine compared to control (non-stressed; NS) females, whereas PS
      males and NS males did not differ. PS enhanced the corticosterone response to
      restraint in male rats previously sensitized to nicotine and decreased the
      corticosterone response in nonsensitized male rats. In contrast, PS females and
      NS females did not differ in plasma corticosterone levels in response to
      restraint stress, but NS females showed enhanced corticosterone release to
      restraint after sensitization to nicotine. Thus, during adolescence, social
      stressors can have long-lasting effects, and the effects appear to differ for
      males and females.

PMID- 15465533
TI  - Acute progesterone can recruit sex-specific neurochemical mechanisms mediating
      swim stress-induced and kappa-opioid analgesia in mice.
AB  - There is a qualitative sex difference in the neurochemical mediation of stress
      induced and kappa-opioid analgesia; these phenomena are dependent on N-methyl-d
      aspartic acid (NMDA) receptors in males but not females. Progesterone modulation
      of this sex difference was examined in mice. Analgesia against thermal
      nociception was produced by forced cold water swim or by systemic administration
      of the kappa-opioid agonist, U50,488. As seen previously, the NMDA receptor
      antagonist MK-801 blocked both forms of analgesia in male but not female mice.
      Also as in previous studies, this sex difference was found to be dependent on
      ovarian hormones such that ovariectomy induced female mice to "switch" to the
      male-like, NMDAergic system. We now demonstrate that a single injection of
      progesterone (50 microg), systemically administered 30 min before analgesia
      assessment, is sufficient to restore female-specific mediation of analgesia
      (i.e., insensitivity to MK-801 blockade) in ovariectomized female mice. The
      rapidity of this neurochemical "switching" action of progesterone suggests
      mediation via cell surface receptors or the action of neuroactive steroid
      metabolites of progesterone.

PMID- 15465534
TI  - Social parameters and urinary testosterone level in male chimpanzees (Pan
      troglodytes).
AB  - Studies investigating relationships between social parameters (such as dominance
      rank, rates of aggressive and sexual behaviors) and androgen (particularly,
      testosterone) levels in male primates have yielded inconsistent results. In the
      present study, we address the relationship between androgens, male dominance rank
      and rank-associated behaviors in two groups of captive chimpanzees, a species
      characterized by a pronounced dominance hierarchy between adult males. By
      combining behavioral observations with urinary testosterone (T) measurements, we
      found that the differences in T concentrations between males were small and not
      obviously related to their dominance rank. T levels were not related to the rates
      of initiated aggression and copulatory behavior, but a significant negative
      relationship between male T level and the rates of strong aggression received was
      apparent. Our findings, combined with those of others, suggest that any
      relationship between dominance rank and T depends upon the extent to which
      individual rank-associated behaviors (e.g. aggressive/sexual) are themselves
      related to T.

PMID- 15465535
TI  - Background matters: the effects of estrogen receptor alpha gene disruption on
      male sexual behavior are modified by background strain.
AB  - One approach to study interactions between behavior and genetics is to use inbred
      mice with different genetic backgrounds. To examine the effect of background on a
      specific gene, we conducted a series of experiments with a well-characterized
      knockout (KO) mouse, the estrogen receptor alpha KO (ERalphaKO). The ERalphaKO
      mouse has so far been examined in one inbred line, C57BL/6J. Here, we examined
      the behavior of ERalphaKO mice within three different backgrounds mixed with
      C57BL/6J; DBA/2J, BALB/c, and A/J. First, we assessed masculine sexual behavior
      in both intact male and testosterone-treated female offspring. More ERalphaKO
      males in the DBA/2J (5/12) and BALB/c (5/13) backcrosses displayed intromissions
      and many ejaculated as compared with males in a C57BL/6J and A/J mixed
      background. Many fewer ERalphaKO females than males displayed masculine sexual
      behavior in any of the three hybrid crosses. We assessed fertility in males from
      the C57BL/6J by DBA/2J cross and found that one of 12 ERalphaKO males sired a
      litter. Several other characteristics of sexual behavior and physiology were
      unaffected by genetic background in ERalphaKO mice. Our data suggest that genetic
      background has dramatic effects on male sexual behavior and its dependence on the
      ERalpha gene.

PMID- 15465536
TI  - The role of androgens in the trade-off between territorial and parental behavior
      in the Azorean rock-pool blenny, Parablennius parvicornis.
AB  - Androgen hormones have been shown to facilitate competitive ability in courtship
      and territorial behavior, while suppressing paternal behavior. The rock-pool
      blenny, Parablennius parvicornis, provides an excellent model to study the
      proximate regulation of such a trade-off between territorial and parental
      behavior, because nest-holder males of this species display these behaviors
      simultaneously. A field study was carried out in which territorial nest holder
      males were either treated with long-lasting implants filled with 11
      ketotestosterone (11-KT) or with control implants. Males treated with 11-KT
      showed a higher frequency of aggressive behavior, were more responsive to
      aggressive challenges, and were more persistent in aggressive behavior than
      control males. In addition, territories were larger in males treated with 11-KT
      than in controls. We found evidence for incompatibility between defense of a
      large territory and high levels of parental behavior. However, contrary to
      expectation, 11-KT did not suppress parental behavior. We suggest that trade-offs
      between territorial and parental behavior may not be regulated by androgen
      hormones but may result from a time constraint in the individual's activity
      budget.

PMID- 15465537
TI  - Prolactin-induced parental hyperphagia in ring doves: are glucocorticoids
      involved?
AB  - Hyperphagia is a prominent component of the parental behavior repertoire in male
      and female ring doves and is necessary in order for parents to successfully
      provision their growing young. Although previous studies implicate both prolactin
      and the endogenous glucocorticoid, corticosterone, in parental hyperphagia, the
      functional interactions between these two hormones in regulating changes in
      feeding activity have not been characterized. These studies examined the
      possibility that prolactin's orexigenic effects are mediated through the
      increased secretion of corticosterone. Twice-daily intracerebroventricular (icv)
      injection of prolactin increased plasma corticosterone concentration in non
      breeding doves of both sexes, with males exhibiting more pronounced effects than
      females. To further test the importance of glucocorticoid signaling in prolactin
      induced feeding responses, changes in food intake were investigated in icv
      prolactin-treated, non-breeding doves following icv infusion of the
      glucocorticoid receptor antagonist RU38486 or propylene glycol vehicle. No
      attenuation of prolactin-induced hyperphagia was observed in either sex following
      co-administration of RU38486 at a dose shown previously to block dexamethasone
      induced feeding in doves. These findings suggest that elevated corticosterone
      titers in blood may contribute to the hyperphagia observed in response to
      prolactin, but corticosterone signaling through a mammalian-type glucocorticoid
      receptor is not essential.

PMID- 15465538
TI  - PRK after 12 years: good news for patients.

PMID- 15465539
TI  - Trials and tribulations: a primer on successfully navigating the waters of the
      Food and Drug Administration.
AB  - Conducting clinical trials in a regulated environment constitutes unfamiliar
      territory for most physicians. There exists no formal training in this subject,
      so many clinicians lack even a basic understanding of the procedures required by
      the Federal Food, Drug, and Cosmetic Act and their implications vis-a-vis
      clinical practice. The authors distill drug regulation to relevant applications
      and elucidate the rationale and procedures for submitting an Investigational New
      Drug application by providing a user-friendly road map of the process.

PMID- 15465540
TI  - Managing the new mandate in resident education: a blueprint for translating a
      national mandate into local compliance.
AB  - OBJECTIVE: The Accreditation Council for Graduate Medical Education (ACGME) has
      mandated that all residency programs implement an assessment process of 6 core
      competencies. Assessment of surgical competence is also included in the mandate.
      We describe our local efforts to meet this new mandate. DESIGN: Systematic
      literature review. METHODS: A systematic MEDLINE search (1996-2003) of the
      literature on residency assessment tools was performed. All relevant titles were
      reviewed by a content expert, abstracts were selected, and all appropriate full
      articles were reviewed. The Department of Ophthalmology at the University of Iowa
      formalized the competency review process by forming an ad hoc departmental task
      force for "Meeting the Competencies" composed of clinicians, technical staff,
      education specialists, the program director, the director of residency
      curriculum, the medical student director, and residents. RESULTS: The task force
      reviewed the available literature, reviewed potential best practices, and reached
      consensus on an implementation plan. The following specific criteria for the
      assessment process were proposed: (1) there should be multiple assessments by
      multiple observers using multiple tools at multiple time points, (2) the tools
      should be reliable, reproducible, and valid; (3) the tools must be practical
      (i.e., feasible, convenient, low time commitment, easy to use, and inexpensive to
      implement and maintain); (4) the tools must produce qualitative and quantitative
      data, with direct linkage to improvement in educational outcomes in the future;
      (5) the assessment process must be linked to explicit and public learning
      objectives; and (6) the grading scale should be open and clearly defined, and the
      process should be judged as fair and accurate by both faculty and residents. The
      Meeting the Competencies task force reviewed all of the available tools from the
      literature and recommended a pilot implementation matrix matching specific tools
      to individual competencies. The 6 pilot tools include (1) written and oral
      examinations, (2) a 360 degrees global evaluation form (using multiple observers
      from different perspectives, including nurses, technicians, fellow residents, and
      patients, to provide a wider assessment), (3) a resident portfolio, (4) direct
      observation of operative performance and clinical examination, (5) a phone
      encounter tool, and (6) a journal club tool. CONCLUSION: We propose a potential
      blueprint for meeting the challenge of assessing the new ACGME competencies in
      ophthalmology and translating the national mandate into local compliance.

PMID- 15465541
TI  - A long-term study of photorefractive keratectomy; 12-year follow-up.
AB  - OBJECTIVE: To evaluate long-term refractive stability of excimer laser myopic
      photorefractive keratectomy (PRK). DESIGN: A long-term (12 years) prospective
      follow-up study. PARTICIPANTS: Sixty-eight patients (56.6%) of the original
      cohort of 120 who participated in the first United Kingdom excimer laser clinical
      trial underwent detailed clinical assessment at 12 years after myopic PRK.
      INTERVENTION: Myopic PRK was performed using the Summit Technology UV 200 excimer
      laser with a 4-mm ablation zone. Patients were allocated to 1 of 6 treatment
      groups based on their preoperative refraction. Each group received one of the
      following spherical corrections: -2, -3, -4, -5, -6, or -7 diopters (D). Patients
      in each group received an identical treatment, and therefore, emmetropia was not
      the primary aim. MAIN OUTCOME MEASURES: Refractive stability, refractive
      predictability, best spectacle-corrected visual acuity (BSCVA), and corneal haze.
      RESULTS: The postoperative refraction remained stable at 12 years, with no
      significant change in mean spherical equivalent refraction between 1, 6, and 12
      years. Seventy-five percent of patients who underwent a -2-D correction and 65%
      of patients who received a -3-D correction were within 1 D of intended correction
      at 12 years. Fifty-seven percent of the -4-D group and 50% of the -5-D group were
      within 1 D, and this was further reduced to 25% and 22% in the -6-D and -7-D
      groups, respectively. Four percent had residual corneal haze, and 12% had
      persistent nighttime halos at 12 years. Dry eyes were encountered in 3% of
      patients, and none of the eyes developed corneal ectasia in the long term.
      CONCLUSIONS: In myopic PRK, refractive stability achieved at 1 year was
      maintained up to 12 years with no evidence of hyperopic shift, diurnal
      fluctuation, or late regression in the long term. Corneal haze decreased with
      time, with complete recovery of BSCVA. Night halos remained a significant problem
      in a subset of patients due to the small ablation zone size.

PMID- 15465542
TI  - Comparison of intraocular lens power calculation methods in eyes that have
      undergone LASIK.
AB  - OBJECTIVE: To compare methods of calculating intraocular lens (IOL) power for
      cataract surgery in eyes that have undergone myopic LASIK. DESIGN: Noncomparative
      case series. PARTICIPANTS: Eleven eyes of 8 patients who had previously undergone
      myopic LASIK (amount of LASIK correction [+/-standard deviation], -5.50+/-2.61
      diopters [D]; range, -8.78 to -2.38 D) and subsequently phacoemulsification with
      implantation of the SA60AT IOLs (Alcon Surgical, Inc., Fort Worth, TX) were
      included (refractive error after cataract surgery, -0.61 +/- 0.79 D; range, -2.0
      to 1.0 D). METHODS: We evaluated the accuracy of various combinations of: (1)
      single-K versus double-K (in which pre-LASIK keratometry is used to estimate
      effective lens position) versions of the IOL formulas; the Feiz-Mannis method was
      also evaluated; (2) 4 methods for calculating corneal refractive power (clinical
      history, contact lens overrefraction, adjusted effective refractive power
      [EffRP(adj)], and Maloney methods); and (3) 4 IOL formulas (SRK/T, Hoffer Q,
      Holladay 1, and Holladay 2). The IOL prediction error was obtained by subtracting
      the IOL power calculated using various methods from the power of the implanted
      IOL, and the F test for variances was performed to assess the consistency of the
      prediction performance by different methods. MAIN OUTCOME MEASURES: Mean
      arithmetic IOL prediction error, mean absolute IOL prediction error, and variance
      of the IOL prediction error. RESULTS: Compared with double-K formulas, single-K
      formulas predicted lower IOL powers than the power implanted and would have left
      patients hyperopic in most cases; the Feiz-Mannis method had the largest
      variance. For the Hoffer Q and Holladay 1 formulas, the variances for EffRP(adj)
      were significantly smaller than those for the clinical history method (0.43 D2
      vs. 1.74 D2, P = 0.018 for Hoffer Q; 0.75 D2 vs. 2.35 D2, P = 0.043 for Holladay
      1). The Maloney method consistently underestimated the IOL power but had
      significantly smaller variances (0.19-0.55 D2) than those for the clinical
      history method (1.09-2.35 D2; P<0.015). There were no significant differences
      among the variances for the 4 formulas when using each corneal power calculation
      method. CONCLUSIONS: The most accurate method was the combination of a double-K
      formula and corneal values derived from EffRP(adj). The variances in IOL
      prediction error were smaller with the Maloney and EffRP(adj) methods, and we
      propose a modified Maloney method and second method using Humphrey data for
      further evaluation.

PMID- 15465543
TI  - Effectiveness of multifocal intraocular lenses to correct presbyopia after
      cataract surgery: a randomized controlled trial.
AB  - PURPOSE: Although monofocal intraocular lenses (IOLs) are effective in improving
      vision after cataract surgery, the loss of accommodation is not restored by
      implantation of these IOLs. Because multifocal IOLs may improve uncorrected
      distance and near vision, we compared the clinical outcome and patient
      satisfaction after implantation of monofocal and multifocal IOLs.
      Sociodemographics, eagerness for spectacle independence (ESI), and neuroticism
      were tested as predictors of satisfaction. DESIGN: Randomized controlled trial.
      PARTICIPANTS: Cataract patients with no ocular comorbidity were operated from
      August 1999 to January 2001; 75 patients were implanted with monofocal IOLs, and
      78 with multifocal IOLs. METHODS: Assessments were made preoperatively (t1), 3
      months after first-eye surgery (t2), and 3 months after second-eye surgery (t3).
      Primary outcomes were obtained by ophthalmic tests, whereas secondary outcomes
      were examined by interviews. MAIN OUTCOME MEASURES: Primary outcomes consisted of
      near and distance visual acuity (VA). Secondary outcomes related to spectacle
      dependence, vision-related functioning, and patient satisfaction. RESULTS: At t3,
      multifocal IOLs showed significantly better uncorrected near VA than monofocal
      IOLs (P<0.01) and an increase in quality ratings of unaided near vision between
      t1 and t3 (on a scale of 1-5: 1.6 at t1 vs. 2.9 at t3, P<0.001). At t2 and t3,
      patients with multifocal IOLs were more likely to "never" or "only now and then"
      wear spectacles for near and distance than patients with monofocal IOLs (at t3,
      42.7% multifocal vs. 21.6% monofocal for near [P = 0.002] and 75.0% multifocal
      vs. 46.2% monofocal for distance [P = 0.001]). On a 0- to 15-point scale,
      monofocal IOL patients showed fewer complaints from cataract symptoms, including
      halos and distorted vision, at t3 (1.2 monofocal vs. 2.1 multifocal [P = 0.002]).
      Satisfaction related to preoperative expectations was similar in the monofocal
      and multifocal groups. The perceived quality of corrected near vision had the
      strongest relationship with patient satisfaction (beta = 0.22; 95% confidence
      interval: 0.060-0.523). Sociodemographics, ESI, and neuroticism did not predict
      patient satisfaction. CONCLUSIONS: Overall, patient satisfaction did not differ
      between the groups of monofocal and multifocal IOLs. Independent of ESI or
      neuroticism scores, success of both IOLs depends on preoperative expectations and
      postoperative quality of aided near vision. This article contains additional
      online-only material available at .

PMID- 15465544
TI  - Comparison of posterior capsule opacification between the 1-piece and 3-piece
      Acrysof intraocular lenses: two-year results of a randomized trial.
AB  - PURPOSE: To compare intensity of posterior capsule opacification (PCO) between
      the 1-piece and 3-piece haptic designs of an open-loop hydrophobic acrylic
      intraocular lens (IOL). DESIGN: A randomized, patient- and examiner-masked
      clinical trial with intraindividual comparison. PARTICIPANTS: Fifty-two patients
      with bilateral age-related cataract (104 eyes). METHODS: Each patient had
      cataract surgery in both eyes and received a 1-piece Acrysof IOL in one eye and a
      3-piece Acrysof IOL in the fellow eye. Follow-up examinations were at 1 week, 1
      month, 6 months, 1 year, and 2 years. Patients were examined at the slit lamp,
      visual acuity (VA) was determined, and standardized high-resolution digital
      retroillumination images of the posterior capsule were taken. The intensity of
      PCO was assessed subjectively at the slit lamp and objectively using automated
      image analysis software. MAIN OUTCOME MEASURE: Posterior capsule opacification
      score (scale, 0-10). RESULTS: There was no significant difference between IOL
      styles in best-corrected VA, rhexis/IOL overlap, capsular folds, and amount of
      anterior capsule opacification during the follow-up period. One year
      postoperatively, the amount of regeneratory PCO was higher for the 1-piece
      Acrysof eyes (image analysis software score: 1.3) than for the 3-piece Acrysof
      eyes (score: 0.9; P = 0.002). However, 2 years postoperatively, there was no
      significant difference between the 2 IOL styles (1-piece: 1.5; 3-piece: 1.3; P =
      0.3). Neodymium:yttrium-aluminum-garnet capsulotomy was not performed in the
      study. CONCLUSION: One year postoperatively, the 1-piece Acrysof showed slightly
      more regeneratory PCO than the 3-piece Acrysof. However, 2 years postoperatively,
      the barrier effect of the 1-piece design was comparable to that of the 3-piece
      haptic design, with low PCO intensity.

PMID- 15465546
TI  - Comparison of long-term outcomes of selective laser trabeculoplasty versus argon
      laser trabeculoplasty in open-angle glaucoma.
AB  - PURPOSE: To compare the long-term success rate of selective laser trabeculoplasty
      (SLT) versus argon laser trabeculoplasty (ALT). DESIGN: Retrospective chart
      review. PARTICIPANTS: One hundred ninety-five eyes of 195 patients with
      uncontrolled open-angle glaucoma (OAG), of which 154 eyes underwent ALT and 41
      eyes underwent SLT and were followed up for a maximum of 5 years. INTERVENTION:
      The SLT patients were treated with the frequency-doubled q-switched
      neodymium:yytrium-aluminum-garnet laser (532 nm). Approximately 50 to 55
      nonoverlapping spots were placed over 180 degrees of the trabecular meshwork at
      energy levels ranging from 0.6 to 1.0 mJ per pulse. The ALT patients were treated
      with the argon blue-green laser with between 45 to 55 adjacent, nonoverlapping
      spots over 180 degrees of the trabecular meshwork at 470 to 1150 mW of energy per
      pulse. MAIN OUTCOME MEASURES: The success rates were defined by criterion I and
      criterion II. Success by criterion I was defined as a decrease in intraocular
      pressure (IOP) of 3 mmHg or more with no additional medications, laser, or
      glaucoma surgery. Criterion II had the same requirements as criterion I, except
      that a 20% or more IOP reduction was required for success. RESULTS: The mean
      follow-up time was 37.4+/-14.7 months for patients in the SLT group and 33.6+/
      17.0 months for patients in the ALT group. The long-term success rate was not
      significantly different between the ALT and SLT groups by either criterion
      (Kaplan-Meier survival analysis log-rank P = 0.20 by criterion I and P = 0.12 by
      criterion II). When comparing patients with and without previous ALT, there was
      not a statistically significant difference in the patients treated with SLT by
      either criterion (log-rank P = 0.37 by criterion I and P = 0.39 by criterion II).
      CONCLUSIONS: In eyes with primary OAG that are receiving maximally tolerated
      medical therapy, SLT was found to be as effective as ALT in lowering IOP over a 5
      year period. However, long-term data reveal that many of the glaucoma patients
      treated with SLT and ALT required further medical or surgical intervention.
      Whether SLT has better long-term success than ALT in repeat laser trabeculoplasty
      treatments remains unclear.

PMID- 15465545
TI  - Ophtec iris reconstruction lens United States clinical trial phase I.
AB  - PURPOSE: To determine the safety and efficacy of the Ophtec model 311 iris
      reconstruction lens for treatment of visual disturbances, such as glare or
      photophobia, related to partial or total absence of the human iris. DESIGN: Phase
      I multicenter, nonrandomized, investigational device study. PARTICIPANTS: Ten
      iris reconstruction lenses were placed in 10 subjects at 6 sites. METHODS: Iris
      reconstruction lenses were placed in 9 patients who had lost all or part of their
      iris from trauma and in 1 patient who lacked iris pigmentation due to congenital
      albinism. Patients were examined preoperatively, intraoperatively, and
      postoperatively at day 1; week 1; and months 1, 3, 6, and 12. MAIN OUTCOME
      MEASURES: Efficacy measures were uncorrected visual acuity (UCVA), glare,
      starbursts, and photophobia. Safety measures were best-corrected visual acuity
      (VA), surgical complications, and adverse events. RESULTS: Uncorrected VA
      improved in all eyes after implantation of the iris reconstruction lens. Best
      corrected VA did not change significantly (P = 0.24). Postoperative photophobia
      was reduced in all 9 eyes that experienced moderate to severe preoperative
      photophobia. Likewise, postoperative glare was reduced in all 6 eyes with
      moderate to severe preoperative glare. There were no surgical complications.
      Adverse events included 2 cases of iritis and 1 case of macular edema.
      CONCLUSIONS: Preliminary results suggest that the Ophtec model 311 iris
      reconstruction lens can improve UCVA and reduce glare and photophobia in patients
      with partial or total absence of the iris or iris pigmentation.

PMID- 15465547
TI  - Diagnostic accuracy of the GDx VCC for glaucoma.
AB  - PURPOSE: To determine the diagnostic accuracy of the GDx VCC in the diagnosis of
      glaucoma. DESIGN: Prospective, comparative, observational, clinic-based case
      series. PARTICIPANTS: One eye each of 77 healthy subjects and 162 patients with
      primary open-angle glaucoma of Caucasian racial origin. Healthy subjects had
      normal visual fields (VFs), healthy-looking optic discs, and intraocular
      pressures of < or =21 mmHg in both eyes. Glaucoma patients had a reproducible
      glaucomatous VF defect and a glaucomatous appearance of the optic disc in at
      least one eye. METHODS: All subjects were measured with the GDx VCC with an
      automated variable corneal compensator. We constructed receiver operating
      characteristic (ROC) curves for all available parameters. Subsequently, we
      calculated sensitivity, specificity, and multilevel likelihood ratios for the
      best discriminating parameter in the entire group. In addition, we calculated
      sensitivity and specificity in patients with mild, moderate, and severe
      glaucomatous damage separately. MAIN OUTCOME MEASURES: Software-derived
      parameters TSNIT (temporal, superior, nasal, inferior, temporal) Average,
      Superior Average, Inferior Average, TSNIT Std. Dev. (standard deviation), and
      Nerve Fiber Indicator (NFI). RESULTS: The areas under the ROC curve for TSNIT
      Average, Superior Average, Inferior Average, TSNIT Std. Dev., and NFI were 0.93,
      0.94, 0.90, 0.92, and 0.98, respectively. For the best discriminating parameter
      NFI, the sensitivity and specificity with a cutoff point of > or =40 were 89.0%
      and 95.9%, respectively. The multilevel likelihood ratios for glaucoma were 0.07
      at NFI values of <35, 1.30 at values between 35 and 44, and 61.50 at values of >
      or =44. At the cutoff level of > or =40, the sensitivities of the NFI for
      correctly identifying glaucoma patients with mild, moderate, and severe damage
      were 83.8%, 92.9%, and 90.1%, respectively. CONCLUSIONS: The GDx VCC allowed
      easy, rapid, and accurate discrimination between healthy and glaucomatous eyes.
      The NFI was the best discriminating parameter. The GDx VCC seems to fulfill
      criteria for a glaucoma screening device.

PMID- 15465548
TI  - Short-wavelength automated perimetry results are correlated with optical
      coherence tomography retinal nerve fiber layer thickness measurements in
      glaucomatous eyes.
AB  - PURPOSE: To determine the relationship between retinal nerve fiber layer (RNFL)
      thickness measured using optical coherence tomography (OCT) and short wavelength
      sensitive visual function measured using short-wavelength automated perimetry
      (SWAP). DESIGN: Retrospective observational case series. METHODS: Subjects were
      recruited from the longitudinal University of California, San Diego, Diagnostic
      Innovations in Glaucoma Study and included 29 glaucoma patients with OCT imaging
      and reliable SWAP visual field (VF) testing within a 6-month window. MAIN OUTCOME
      MEASURES: Correlations between deviation from normal (thinner than 97.5% of
      normal) RNFL measurements taken at 30 degrees sectors (12 sectors described as
      clock hours) and SWAP average pattern deviation within 21 VF zones were
      determined. The number of OCT-measured RNFL sectors outside of normal limits and
      the number of VF zones outside of normal limits also were compared. RESULTS: The
      OCT nerve fiber layer thickness was outside of the normal limits in at least 1
      sector in 26 (89.6%) patients. Twenty-eight (96.5%) patients had at least 1 SWAP
      VF zone outside of normal limits. Optical coherence tomography sectors 6-o'clock,
      7-o'clock, and 8-o'clock (inferior and inferotemporal) and SWAP VF zones 13, 14,
      and 16 (superior hemifield central and arcuate areas) were the most frequently
      damaged. In general, the strongest R2 associations were between inferior and
      inferior temporal RNFL sectors (e.g., 6-o'clock, 7-o'clock) and superior
      nasal/arcuate VF zones (e.g., zones 13, 14, 15) and between superior and superior
      temporal RNFL sectors (e.g., 12-o'clock, 11-o'clock) and inferior central and
      arcuate VF zones (e.g., zones 5, 6, 7) (R2 range = 24.3%-37.3%, all Ps < or =
      0.005). Most nonsignificant associations were found between superior RNFL sectors
      and superior VF zones. CONCLUSION: Retinal nerve fiber layer thickness measured
      with OCT is topographically correlated with glaucomatous VF defects measured with
      SWAP.

PMID- 15465549
TI  - Digital stereoscopic analysis of the optic disc: evaluation of a teaching
      program.
AB  - PURPOSE: To determine if a computer-based stereoscopic teaching program could
      improve optic cup/disc ratio (CDR) agreement between student observers and an
      expert. DESIGN: Experimental study. PARTICIPANTS: Six student observers (A-F)
      assessed at least 30 digital stereoscopic optic disc images using a digital
      stereoscopic analysis program. All observers made 36 CDR measurements (every 10
      degrees ) for each disc image that they assessed. METHODS: Disc images were
      divided into 3 sets of 10 images (image sets 1, 2, and 3). Observers A, B, and C
      determined CDRs for all 3 image sets. Set 1 was examined without access to a
      teaching program, set 2 using a teaching program that allowed the observer to
      view an expert assessment of the optic disc, and set 3 after using the teaching
      program. Observers D, E, and F evaluated image sets 1 and 3 only and did not have
      access to the teaching program. Ten months later, these same observers (D-F)
      viewed image set 2 using the teaching program and then reassessed image set 3.
      MAIN OUTCOME MEASURES: Standard deviation (SD) of CDR differences between
      observers and an expert, the percentage of CDR observations differing > or =0.20
      from those of the expert, and intraclass correlation coefficients (ICCs) between
      observers. RESULTS: Before teaching, the average SD of differences between all
      observers and the expert was 0.10. After teaching, the average SD of differences
      between all observers and the expert was 0.057. For observers D, E, and F, the
      average SD of differences for image set 3 without teaching was 0.074. The
      percentage of all observer measurements that differed > or =0.20 from those of
      the expert for image set 1 was 16.7%; for set 3 after teaching, 1.7%; and for set
      3 for observers D, E, and F without teaching, 10%. Interobserver ICC values for
      all observers were 0.37 before teaching and 0.76 after. For observers D, E, and
      F, the ICC value for set 3 without access to teaching was 0.69. CONCLUSIONS: This
      study suggests that an interactive digital stereoscopic teaching program improves
      agreement between observers and an expert when assessing CDRs.

PMID- 15465550
TI  - Persistent secretion of vascular endothelial growth factor into the vitreous
      cavity in proliferative diabetic retinopathy after vitrectomy.
AB  - PURPOSE: Neovascular glaucoma is a frequent complication of vitrectomy performed
      to treat proliferative diabetic retinopathy (PDR). We assessed the level of
      vascular endothelial growth factor (VEGF) in the vitreous fluid obtained during
      vitrectomy and at postoperative fluid-air exchange. METHODS: We measured VEGF
      levels in vitreous samples from 17 eyes of 15 patients with PDR during vitrectomy
      and fluid samples obtained during fluid-air exchange 5 to 36 days
      postoperatively. Six of the 17 eyes had iris neovascularization after vitrectomy.
      Vascular endothelial growth factor levels also were measured in the vitreous
      fluid obtained from 8 eyes with a macular hole during vitrectomy and
      postoperative fluid-air exchange. We measured the plasma VEGF levels in all
      patients. RESULTS: The mean VEGF levels in 17 eyes with PDR were 1162.3+/-173.2
      pg/ml in the vitreous samples and 1180.4+/-182.8 pg/ml in the postoperative fluid
      samples. The mean plasma VEGF level was 116.1+/-10.2 pg/ml in eyes with PDR, and
      the mean plasma VEGF level was 118.5+/-15.2 pg/ml in patients with a macular
      hole. The mean VEGF levels were 96.9+/-11.5 pg/ml in the vitreous samples and
      73.9+/-12.3 pg/ml in the fluid samples in eyes with a macular hole. CONCLUSIONS:
      A high VEGF level was maintained in the vitreous cavity after vitrectomy for PDR.
      The VEGF level in eyes with PDR was 10 times higher than that in the plasma. The
      results suggest that there is persistent secretion of VEGF into the vitreous
      cavity even after vitrectomy for PDR.

PMID- 15465551
TI  - Persistence of fetal vasculature in a patient with Knobloch syndrome: potential
      role for endostatin in fetal vascular remodeling of the eye.
AB  - OBJECTIVE: To report a child with Knobloch syndrome (KS) with features of
      persistent fetal vasculature (PFV) and to discuss the possible role of endostatin
      in vascular remodeling of the fetal eye. DESIGN: Case report with enzyme-linked
      immunosorbent assay (ELISA) analysis of serum endostatin. MAIN OUTCOME MEASURES:
      Ocular examination, fluorescein angiography, echography, ELISA analysis of serum
      endostatin, and typing for pathogenic mutations in COL18A1. RESULTS: Slit-lamp
      examination in the left eye disclosed numerous findings of PFV, including an
      extensive persistent pupillary membrane, scarcity of iris crypts, and pigmented
      epicapsular stellate remnants on the anterior lens surface. Dilated fundus
      examination revealed a total posterior vitreous detachment, despite the young age
      of the patient, with numerous white intragel opacities that were compatible with
      remnants of the vasa hyaloidea propria. The fundus had a tesselated appearance
      with angiographically visible large choroidal vessels. There was a
      retinochoroidal staphyloma inferotemporal to the optic disc. There were no
      retinal vessels visible temporally, and there was no macular differentiation or
      foveal pit. Competitive ELISA analysis disclosed no detectable serum endostatin.
      None of the 8 reported pathogenic mutations in the COL18A1 gene was found in the
      patient. CONCLUSIONS: Persistent fetal vasculature may be a clinical and
      important manifestation in some patients with KS and can be explained by a
      deficiency in endostatin. Endostatin deficiency may result in reduced or delayed
      regression of fetal blood vessels in the eye (including the intravitreal
      compartment), thereby resulting in incomplete development of the normal
      vasculature in the retina. Our typing results for the reported COL18A1 mutations
      confirm the genetic heterogeneity of KS.

PMID- 15465552
TI  - Macular translocation in patients with recurrent subfoveal choroidal
      neovascularization after laser photocoagulation for nonsubfoveal choroidal
      neovascularization.
AB  - PURPOSE: To report visual outcomes and to examine surgical factors affecting
      outcomes in patients undergoing macular translocation for recurrent subfoveal
      choroidal neovascularization after laser photocoagulation for nonsubfoveal
      choroidal neovascularization. DESIGN: Retrospective, noncomparative,
      interventional case series. PARTICIPANTS: A consecutive series of 31 eyes of 29
      patients who underwent macular translocation for recurrent subfoveal choroidal
      neovascularization after laser photocoagulation for nonsubfoveal choroidal
      neovascularization. INTERVENTION: Inferior macular translocation with punctate
      retinotomy performed by a single surgeon. OUTCOME MEASURES: Surgical and visual
      outcomes at 3 and 6 months after surgery and complications data are reported.
      Associations between surgical factors and visual outcomes were analyzed
      statistically. RESULTS: Effective translocation was achieved in 77.4% of eyes. At
      6 months, 54% of eyes achieved visual acuity (VA) better than 20/100, and 46% of
      eyes gained the equivalent of > or =2 Early Treatment Diabetic Retinopathy Study
      lines of vision. No association between size of recurrent choroidal
      neovascularization and visual outcome was identified. Eyes with a larger scar
      size experienced lower VA at 3 and 6 months, but scar size was not associated
      with change in VA at 3 and 6 months. Subretinal dissection during surgery to
      detach the macula was required in 8 of 31 eyes and was associated with a
      significantly increased incidence of peripheral retinal breaks. However, there
      was no difference in either VA or change in VA in eyes with and without
      subretinal dissection. Retinal detachment (RD) occurred in 6 of 31 eyes. No
      significant difference in the RD rate was observed between groups with or without
      subretinal dissection (P = 0.30). CONCLUSION: Our pilot data suggest that macular
      translocation can result in favorable surgical outcomes in patients with
      recurrent subfoveal choroidal neovascularization after laser photocoagulation for
      nonsubfoveal choroidal neovascularization. Use of subretinal dissection
      intraoperatively in these patients does not seem to affect visual outcome
      adversely, but may be associated with increased risk of peripheral retinal
      breaks.

PMID- 15465553
TI  - Involution of threshold retinopathy of prematurity after diode laser
      photocoagulation.
AB  - OBJECTIVE: To characterize the process of involution of threshold retinopathy of
      prematurity after transpupillary diode laser photocoagulation. DESIGN:
      Retrospective case series. PARTICIPANTS: Neonates with threshold retinopathy who
      underwent diode laser photocoagulation of the peripheral avascular retina.
      METHODS: A retrospective chart review was done of the weekly examination records
      of infants treated for threshold disease. Features that were studied included the
      presence of residual stage 3 neovascularization, plus disease, and development of
      retinal detachment (RD). MAIN OUTCOME MEASURES: Timing of full involution and/or
      development of an RD. RESULTS: Of 262 eyes of 138 infants treated, full
      involution without RD was seen in 8%, 43%, 64%, 73%, and 86% of eyes at
      postoperative weeks 1, 2, 3, 4, and 9+/-3, respectively. Retinal detachments were
      diagnosed cumulatively in 0%, 1.5%, 4.2%, 6.5%, and 14% of eyes at weeks 1, 2, 3,
      4, and 9+/-3, respectively. CONCLUSIONS: Full involution of laser-treated
      threshold retinopathy of prematurity required more than 2 weeks in more than half
      of treated eyes. Most RDs were not detected until > or =3 weeks after treatment.

PMID- 15465554
TI  - Monitoring cystoid macular edema by optical coherence tomography in patients with
      retinitis pigmentosa.
AB  - PURPOSE: To determine the value of optical coherence tomography (OCT) imaging in
      the diagnosis and monitoring of cystoid macular edema (CME) in patients with
      retinitis pigmentosa (RP). DESIGN: Prospective, noncomparative, small case
      series. PARTICIPANTS: Three patients with RP and cystic-appearing spaces in the
      macula on OCT images. INTERVENTION: All 3 patients were treated with a carbonic
      anhydrase inhibitor, and 1 also received topical and systemic steroids. MAIN
      OUTCOME MEASURES: Changes in OCT images, fluorescein angiography, and best
      corrected visual acuity (VA). RESULTS: Although foveal cysticlike spaces were
      evident on OCT images in all 3 patients, only 1 patient showed CME on fluorescein
      angiography at baseline. Two of the 3 patients showed funduscopic evidence of
      macular cystic lesions, whereas a third showed no clinically evident fundus
      changes in the macula. Optical coherence tomography images documented improvement
      in the cystic-appearing spaces after treatment with the carbonic anhydrase
      inhibitor. Changes on fluorescein angiography were either not apparent or
      considerably less apparent. An improvement of > or =1 line on a Snellen acuity
      chart was recorded in 2 patients, whereas a third showed no change of VA in
      either eye. CONCLUSIONS: Optical coherence tomography is a potential method for
      the diagnosis and monitoring of CME in patients with RP. It was more sensitive in
      this regard than either fluorescein angiography or funduscopic examination.

PMID- 15465555
TI  - Clinical findings in a carrier of a new mutation in the choroideremia gene.
AB  - OBJECTIVE: To describe the clinical and molecular findings of a female carrier of
      a new mutation in the choroideremia (CHM) gene. DESIGN: Single interventional
      case report. METHODS: A 27-year-old woman was seen with mild difficulties with
      dark adaptation and a history of a retinal degeneration in her father and
      choroideremia in 3 male paternal first cousins. Visual acuity measurements,
      peripheral and color vision tests, electroretinography (ERG), Goldmann visual
      fields, fluorescein angiogram, computed tomography scan, and DNA analysis were
      performed. MAIN OUTCOME MEASURES: (1) Visual fields, (2) fluorescein angiography,
      and (3) DNA analysis. RESULTS: Visual acuity decreased from 20/30 to 10/200 in
      the right eye abruptly over 2 months, then remained stable over 2 years of follow
      up and remained 20/25 in the left eye. Goldmann visual fields showed development
      of a central scotoma in the right eye concurrent with the rapid decline. A small
      amount of subretinal hemorrhage was visible on dilated fundus examination at that
      time, but definite leakage was not evident on fluorescein angiography;
      afterwards, a choroidal neovascular membrane (CNV) was suspected. The ERG was
      normal. DNA analysis revealed that the patient was heterozygous for a previously
      undescribed substitution mutation at the 3'-splice site of intron 6 of the CHM
      gene (850-1 G to C), confirmed by mRNA analysis with reverse transcriptase
      polymerase chain reaction. CONCLUSIONS: Severe visual acuity loss rarely occurs
      in female carriers of choroideremia mutations. The diagnosis should be considered
      in patients with a suitable family history and fundus findings. Physicians should
      consider the possibility of CNV development in such patients, which may be a
      response to abnormal retinal pigment epithelium. Recognition of this new mutation
      may help identify patients who could benefit from current and future treatments
      to protect against vision loss.

PMID- 15465556
TI  - A novel IMPDH1 mutation (Arg231Pro) in a family with a severe form of autosomal
      dominant retinitis pigmentosa.
AB  - PURPOSE: To define ophthalmic findings in a family with autosomal dominant
      retinitis pigmentosa and a novel IMPDH1 gene mutation. DESIGN: Genetic and
      observational family study. PARTICIPANTS: Sixteen affected members of a family
      with autosomal dominant retinitis pigmentosa. METHODS: Ophthalmic examination,
      including best-corrected visual acuity (VA), slit-lamp biomicroscopy, direct and
      indirect ophthalmoscopy, Goldmann kinetic perimetry, and electroretinography were
      performed. Deoxyribonucleic acid single-strand conformation polymorphism (SSCP)
      analysis was done. Abnormal polymerase chain reaction products identified by SSCP
      analysis were sequenced bidirectionally. RESULTS: All affected patients had the
      onset of night blindness within the first decade of life. Ocular findings were
      characterized by diffuse retinal pigmentary degenerative changes, marked
      restriction of peripheral visual fields, severe loss of VA, nondetectable
      electroretinography amplitudes, and a high frequency of posterior subcapsular
      lens opacities. Affected members were observed to harbor a novel IMPDH1 gene
      mutation. CONCLUSION: A novel IMPDH1 gene mutation (Arg231Pro) was associated
      with a severe form of autosomal dominant retinitis pigmentosa. Families affected
      with a severe form of this genetic subtype should be investigated for a mutation
      in the IMPDH1 gene.

PMID- 15465557
TI  - Causes of chemoreduction failure in retinoblastoma and analysis of associated
      factors leading to eventual treatment with external beam radiotherapy and
      enucleation.
AB  - PURPOSE: To evaluate the causes of chemoreduction failure in retinoblastoma and
      to analyze the associated factors for eventual treatment with external beam
      radiotherapy and enucleation. DESIGN: Prospective noncomparative case series.
      PARTICIPANTS: Seventy-one patients with 105 eyes with intraocular retinoblastoma
      that underwent chemoreduction therapy between October 1998 and January 2003.
      INTERVENTION: A 6-treatment cycle of chemoreduction therapy with vincristine,
      etoposide, and carboplatin was administered at monthly intervals. Unresponsive
      disease was defined as persistence of retinal tumors, vitreous seeds, or
      subretinal seeds after the second treatment cycle, with no appreciable sign of
      regression. Eyes with unresponsive disease were enucleated after the second
      treatment. Eyes that responded to chemoreduction therapy received focal
      treatment, including indirect laser photocoagulation, transpupillary
      thermotherapy, cryotherapy, and ruthenium 106 episcleral plaque radiotherapy
      after the second chemoreduction treatment, if necessary, to achieve complete
      tumor regression. Recurrence was defined as the regrowth of retinal tumors,
      vitreous or subretinal seeds after an initial favorable response, and regression.
      Recurrent retinal tumor, vitreous seeds, or subretinal seeds were treated with
      focal treatments and 2 to 3 additional chemoreduction treatments. When these
      methods failed or were not applicable, external beam radiotherapy and/or
      enucleation was administered. MAIN OUTCOME MEASURES: The use of external beam
      radiotherapy and enucleation for chemoreduction failure, which was defined as
      unresponsive or recurrent disease. RESULTS: The mean follow-up was 25.7 months
      (range: 6-49). Ten of 105 eyes (9.5%) with unresponsive disease were enucleated
      after the second treatment. Of the remaining 95 eyes, 42 (44.2%) developed
      recurrence after chemoreduction. Recurrent disease failing to be treated
      successfully by other methods was treated with external beam radiotherapy in 26
      of 95 eyes (27.4%) and enucleation in 22 of 95 eyes (23.2%). External beam
      radiotherapy was successful in preventing enucleation in 20 of 26 eyes (76.9%).
      Overall, the globe salvage rate was 69.5%, ranging from 36.1% for Reese-Ellsworth
      group V disease to 87.0% for groups I to IV disease. Histopathologically, 29 of
      31 enucleated eyes (93.5%) had poorly differentiated or moderately differentiated
      retinoblastoma. Using multivariate logistic regression analysis, factors
      predictive of eventual treatment with external beam radiotherapy were female
      gender (P = 0.010), presence of subretinal seeds (P = 0.023), and a greater
      number of chemoreduction treatments (P = 0.027). By multivariate analysis, the
      factors associated with the need for eventual treatment with enucleation were
      recurrence of retinal tumors (P = 0.004), presence of vitreous seeds (P = 0.008),
      greater tumor thickness (P = 0.015), presence of subretinal fluid (P = 0.040),
      and older patient age (P = 0.042). CONCLUSIONS: Chemoreduction failure in this
      article was defined as unresponsive or, more commonly, recurrent retinoblastoma.
      Older patient age, greater tumor thickness, presence of vitreous seeds and
      subretinal fluid at baseline, and retinal tumor recurrence after chemoreduction
      were factors associated with the need for enucleation.

PMID- 15465558
TI  - The Australian Mohs database: periocular squamous intraepidermal carcinoma.
AB  - OBJECTIVE: To present the findings and report the outcomes of all patients with
      periocular squamous intraepidermal carcinoma (IEC) treated with Mohs micrographic
      surgery (MMS) in Australia between 1993 and 1999. DESIGN: Prospective,
      noncomparative, multicenter, interventional case series. METHODS: A prospective
      series of 53 patients undergoing MMS for periocular IEC over a 7-year period
      (1993-1999). MAIN OUTCOME MEASURES: Recurrence, site, size of IEC, prior
      recurrence, and size of final defect. RESULTS: Fifty-three patients had 27 (51%)
      lower eyelid, 17 (32%) medial canthus, and 9 (17%) upper eyelid IEC. Most (85%)
      of the IECs were present for less than 5 years. Fifty-eight percent were primary
      IECs, and 42% were recurrent IECs. There were no differences in the clinical
      features of primary and recurrent IECs. Significant subclinical tumor extension
      was found, whereby the defect exceeded tumor size by at least 2 size groups (> or
      =2 cm) in 25% of cases. Follow-up to date was available in 68% (36 of 53) of
      cases (19 primary and 17 recurrent IECs). With a mean follow-up of 77.4 months
      (median, 75; range, 44-120 months), 3 (8.3%; exact 95% confidence interval 1.8%
      23.1%) cases recurred. Hence, the recurrence rate was 5.3% (1 of 19) for primary
      periocular IEC and 11.8% (2 of 17) for recurrent periocular IEC. CONCLUSIONS: The
      Australian MMS database provides data for the first prospective series of
      periocular IEC managed by MMS. Periocular IEC demonstrates significant
      subclinical tumor extension, with no significant differences in the clinical
      features of primary and recurrent lesions. Compared with other published studies,
      the recurrence rate of 5% and 12% for primary and recurrent lesions,
      respectively, with more than 5-years of follow-up for most cases emphasizes the
      importance of margin-controlled excision for periocular IEC.

PMID- 15465559
TI  - Patterns of regional and distant metastasis in patients with eyelid and
      periocular squamous cell carcinoma.
AB  - PURPOSE: To determine the frequency and location of regional lymph node
      metastasis in patients with squamous cell carcinoma (SCC) of the eyelid and
      periocular skin. Patterns of distant metastasis were also investigated. DESIGN:
      Retrospective case series. PATIENTS: One hundred eleven patients treated at The
      University of Texas M. D. Anderson Cancer Center for SCC of the eyelid and
      periocular skin between 1952 and 2000. METHODS: The clinical records of the 111
      patients were retrospectively reviewed. The clinical characteristics analyzed
      included age, gender, location of lesion, treatment modalities, patterns of
      regional nodal and distant metastasis, and perineural invasion. Follow-up time
      ranged from 6 to 484 months (median, 76.6). MAIN OUTCOME MEASURE: Incidence of
      regional lymph node metastasis. RESULTS: The most common sites of SCC were the
      lower eyelid (54 patients [48.6%]), the medial canthus (40 patients [36.0%]), and
      the upper eyelid (25 patients [22.5%]). Local treatment of SCC consisted of wide
      local excision with frozen section analysis to ensure negative margins in 96
      patients (86.4%), radiotherapy (without surgery) in 7 patients, and primary
      exenteration because of extensive tumor in 7 patients. Local recurrence occurred
      in 41 patients (36.9%). Twenty-seven patients (24.3%) had regional nodal
      metastasis during the study period. Sixteen of these patients had regional lymph
      node metastasis at the time of the initial presentation to M. D. Anderson Cancer
      Center. Eleven developed regional nodal disease later. Seven patients (6.2%) had
      distant metastasis during the study period. Nine patients (8.1%) had perineural
      invasion. CONCLUSION: This study indicates that the overall rate of regional
      lymph node metastasis in patients with SCC of the eyelid or periocular skin may
      be as high as 24%. Thus, careful surveillance of the regional lymph nodes is an
      important aspect of the initial management of eyelid or periocular skin SCC.
      Consideration could be given to studying sentinel lymph node biopsy as a
      technique to stage SCC of the eyelid or periocular skin more accurately,
      especially in patients with recurrent, large, or highly invasive lesions or with
      perineural invasion.

PMID- 15465560
TI  - Conjunctival metastasis as initial sign of disseminated cutaneous melanoma.
AB  - PURPOSE: To describe a patient with conjunctival metastasis as the initial
      manifestation of metastasis from a cutaneous melanoma. DESIGN: Single
      interventional case report. METHODS: A 48-year-old woman with a history of
      cutaneous axillary melanoma developed a rapidly growing conjunctival mass.
      Subsequent systemic evaluation disclosed asymptomatic liver metastasis. The
      conjunctival lesion was resected. RESULTS: Histopathologic evaluation of the
      conjunctival tumor disclosed an epithelioid cell melanoma located in the
      conjunctival stroma, without appreciable junctional activity, compatible with
      metastatic melanoma. CONCLUSIONS: Conjunctival metastasis from cutaneous melanoma
      can rarely be the initial manifestation of disseminated melanoma.

PMID- 15465563
TI  - Glaucoma treatment outcomes.

PMID- 15465561
TI  - Characteristic retinal atrophy with secondary "inverse" optic atrophy identifies
      vigabatrin toxicity in children.
AB  - OBJECTIVE: To describe the clinical pattern of retinal atrophy in children caused
      by the anticonvulsant vigabatrin. DESIGN: An interventional case series report.
      PARTICIPANTS: One hundred thirty-eight patients, mainly infants, were evaluated
      regularly for evidence of possible vigabatrin toxicity in the Eye and Neurology
      clinics at the Hospital for Sick Children, Toronto. METHOD: Sequential clinical
      and electroretinographic (International Society for Clinical Electrophysiology of
      Vision standards) evaluations every 6 months. MAIN OUTCOME MEASURES: Presence of
      recognizable retinal and optic atrophy in the presence of abnormal
      electroretinogram (ERG) and other clinical findings. RESULTS: Three children
      being treated for seizures with vigabatrin showed definite clinical findings of
      peripheral retinal nerve fiber layer atrophy, with relative sparing of the
      central or macular portion of the retina and relative nasal optic nerve atrophic
      changes. Some macular wrinkling was evident in 1 case. Progressive ERG changes
      showing decreased responses, especially the 30-Hz flicker response, supported the
      presence of decreased retinal function. CONCLUSIONS: A recognizable and
      characteristic form of peripheral retinal atrophy and nasal or "inverse" optic
      disc atrophy can occur in a small number of children being treated with
      vigabatrin. The changes in superficial light reflexes of the retina in children
      facilitate the clinical recognition of nerve fiber layer atrophy. The macula is
      relatively spared, although superficial retinal light reflexes indicating
      wrinkling of the innermost retina suggest early macular toxicity as well. Because
      these changes are accompanied by electrophysiologic evidence of retinal
      dysfunction, discontinuation of vigabatrin should be strongly considered.

PMID- 15465564
TI  - Radiation retinopathy after therapy for meningioma.

PMID- 15465566
TI  - Variation in diabetic macular edema.

PMID- 15465568
TI  - Variation in diabetic macular edema.

PMID- 15465570
TI  - Variation in diabetic macular edema.

PMID- 15465571
TI  - Adaptive and maladaptive self-focus in depression.
AB  - BACKGROUND: Studies of rumination suggest that self-focused attention is
      maladaptive and perpetuates depression. Conversely, self-focused attention can be
      adaptive, facilitating self-knowledge and the development of the alternative
      functional interpretations of negative thoughts and feelings on which cognitive
      therapy of depression depends. Increasing evidence suggests there are distinct
      varieties of self-focus, each with distinct functional properties. This study
      tested the prediction that in depressed patients brief inductions of analytical
      versus experiential self-focus would differentially affect overgeneral
      autobiographical memory, a phenomenon associated with poor clinical course. It
      was predicted that, relative to analytical self-focus, experiential self-focus
      would reduce overgeneral memory. METHODS: 28 depressed patients either thought
      analytically about, or focused on their momentary experience of, identical
      symptom-focused induction items from [Cogn. Emotion 7 (1993) 561] rumination
      task. Participants completed the Autobiographical Memory Test [J. Abnorm.
      Psychol. 95 (1986) 144] before and after self-focus manipulations. RESULTS:
      Experiential self-focus reduced overgeneral memory compared to analytical self
      focus. Analytical and experiential self-focus did not differ in their effects on
      mood. LIMITATIONS: In the absence of a reference condition, only conclusions
      concerning the relative effects of analytical and experiential self-focus can be
      made. CONCLUSIONS: Results (1) support the differentiation of self-focus into
      distinct modes of self-attention with distinct functional effects in depression;
      (2) provide further evidence for the modifiability of overgeneral memory; and (3)
      provide further evidence for the dissociation of overgeneral memory and depressed
      mood. Clinically, results support the usefulness of training recovered depressed
      patients in adaptive experiential forms of self-awareness, as in mindfulness
      based cognitive therapy.

PMID- 15465572
TI  - Child and adolescent clinical features as forerunners of adult-onset major
      depressive disorder: retrospective evidence from an epidemiological sample.
AB  - BACKGROUND: Adult-onset cases of DSM-III-R major depressive disorder (MDD) often
      have had a history of mood disturbances and allied clinical features during
      childhood or adolescence. This study seeks to illuminate these early-life
      disturbances, as recalled and reported by adult-onset MDD cases (i.e. those whose
      first episode of MDD occurred after age 18) and non-cases. METHODS: Our research
      group has re-assessed survivors in the Baltimore Epidemiologic Catchment Area
      (ECA) community sample roughly 13.5 years after first diagnostic assessments in
      1981. Of the 1920 participants, 150 were found to have a history of adult-onset
      MDD; 1755 were sub-threshold with respect to DSM criteria or reported few or no
      depression-related problems. Survival analysis was used to plot and study the
      cumulative occurrence of each clinical feature of depression from age 6 through
      18 years for cases of adult-onset MDD versus non-cases. RESULTS: The earliest and
      most frequently occurring forerunners of adult-onset MDD were persistent
      depressed mood, anhedonia, feelings of worthlessness, and thoughts of death or
      suicide, with persistent anhedonia and worthlessness having a special prognostic
      value. One-third of adult-onset cases of MDD reported at least one clinical
      feature before age 19 versus only 7.3% of non-cases. LIMITATIONS: The study's
      estimates are based on retrospective recall, although a life chart methodology
      sought to reduce recall inaccuracies. CONCLUSIONS: The ECA follow-up sample data,
      though based on retrospection, provide new details about early forerunners of
      adult-onset depression from a sample of survivors. When they appear in children
      or adolescents, persistent anhedonia and persistent feelings of worthlessness
      merit special attention. These two clinical features, in particular, may help
      predict later risk of adult-onset major depression.

PMID- 15465573
TI  - Clinical features related to age at onset in bipolar disorder.
AB  - BACKGROUND: Early age at illness onset has been associated with poor functional
      and syndromal outcome in bipolar disorder, although debate remains about the
      likely robustness of this variable, especially while controlling for other
      illness parameters. METHOD: Fifty-six consecutive bipolar outpatients underwent
      semistructured interviews to assess psychopathology and outcome. We hypothesized
      that early age at onset would be linked with more prevalent rapid cycling,
      psychosis, comorbid substance abuse, and suicide attempts. RESULTS: Illness onset
      before age 19 arose in 46% of subjects. Separate logistic regression analyses
      revealed that onset before age 19 was associated with developing comorbid
      substance abuse/dependence (OR=7.714, 95% CI=1.863-31.944, Wald chi(2)=7.949,
      df=1, P=0.005), as well as the eventual development of rapid cycling (OR=6.000,
      95% CI=1.250-25.893, Wald chi(2)=5.348, df=1, P=0.021). No significant or near
      significant associations were observed between age at onset and lifetime suicide
      attempts or lifetime psychosis. After an initial manic or mixed episode, delaying
      the introduction of antidepressants tended to be protective against the eventual
      development of rapid cycling (OR=0.927, 95% CI=0.856-1.004, Wald chi(2)=3.440,
      df=1, P=0.064). LIMITATIONS: The sample size may have been too small to detect
      group differences of small magnitude. The use of retrospective life chart
      assessments to ascertain age at onset and lifetime illness course may impose
      limitations on generalizability in the absence of prospective data. CONCLUSIONS:
      Early onset of bipolar illness appears related to the development of rapid
      cycling and of comorbid substance abuse/dependence. The findings raise
      developmental implications for the pathogenesis of illness complexity and poor
      outcome states.

PMID- 15465575
TI  - The suicidal process; prospective comparison between early and later stages.
AB  - BACKGROUND: Mechanisms contributing to suicidal behaviour may differ according to
      how far individuals have progressed through the suicidal process. METHODS:
      Lifetime and subsequent 12-month cumulative incidences were obtained of death
      ideation, death wishes, suicide contemplation and deliberate self-harm in a
      survey (n=5618) of Dutch adults. Mokken's scale analysis was used to examine
      whether these were compatible with underlying lifetime and 12-month severity
      dimensions of suicidality. Sociodemographic details and personality traits, 12
      month occurrence of negative life events, hopelessness and CIDI-generated DSM-III
      R diagnoses were obtained. Ordered logistic regression was used to examine
      whether the effects of these on the 12-month incidence of suicidality differed by
      individuals' prior lifetime history of suicidality. RESULTS: Mental illness was
      more strongly associated with 12-months' suicidality in the presence (ordered
      logistic regression coefficient 0.80, 95% confidence interval 0.48-1.12) than the
      absence of previous suicidality (0.49 [0.25-0.74]). The reverse obtained for
      negative life events (0.18 [0.08-0.29] vs. 0.40 [0.33-0.48], respectively) and a
      number of sociodemographic risk factors. Female gender was a risk factor for 12
      months' suicidality (0.47 [0.28-0.66]) only when it was first-onset. LIMITATIONS:
      Completed suicides were not recorded. Self-report of lifetime suicidal behaviour
      may be biased. CONCLUSION: Environmental influences on suicidal behaviour are
      most pronounced early in the suicidal process which, after it has progressed,
      becomes more autonomous and intricately linked with mental illness and depression
      in particular. Men progress through the suicidal process faster than women.
      Management of suicidal behaviour depends on the stage of the process the person
      is at.

PMID- 15465574
TI  - The Impact of Event Scale--Revised: evaluation of the subscales and correlations
      to psychophysiological startle response patterns in survivors of a life
      threatening cardiac event: an analysis of 129 patients with an implanted
      cardioverter defibrillator.
AB  - BACKGROUND: The aim of the present study was to examine the reliability and
      validity of the Impact of Event Scale-Revised (IES-R) with special emphasis on
      the evaluation of the hyperarousal subscale against a standardized
      psychophysiological measurement. METHODS: A total of 129 survivors of a life
      threatening cardiac event underwent a psychodiagnostic evaluation and a
      psychophysiological acoustic startle reflex (ASR) paradigm. The ASR assessed the
      magnitude and habituation of electromyogram (EMG) and skin conductance responses
      (SCR) in response to the delivery of 15 acoustic startle trials. Pearson
      correlation and factor analysis was used to measure reliability and construct
      validity. The hyperarousal subscale was validated against the ASR in terms of
      sensitivity and specificity mainly using receiver operating characteristic (ROC)
      curve analysis. RESULTS: A high reliability was found for the intrusion and
      avoidance subscale (alpha>0.8); however, the hyperarousal subscale showed a
      weaker reliability (alpha=0.66). No avoidance item, one intrusion item but four
      hyperarousal items revealed higher correlations to another than its assigned
      subscale. The hyperarousal subscale was not able to discriminate sufficiently
      between patients with and without exaggerated startle reactions as indicated by
      ROC curves running near the diagonal line. LIMITATIONS: The scores in all three
      subscales are lower compared to subjects traumatized by non-cardiac events.
      CONCLUSIONS: Reliability and construct validity for the intrusion and avoidance
      subscale proved to be high but was only sufficient for the hyperarousal subscale.
      Moreover, the criterion validity of the hyperarousal subscale regarding
      psychophysiological measurements is arguable and indicates further investigations
      in this area.

PMID- 15465576
TI  - Age effects on cortisol levels in depressed patients with and without comorbid
      post-traumatic stress disorder, and healthy volunteers.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) and major depression are
      frequently comorbid. Age and major depression are associated with higher cortisol
      levels and dexamethasone resistance, whereas PTSD is associated with lower
      cortisol and dexamethasone supersensitivity. Therefore, we examined the effect of
      age on the hypothalamic-pituitary-adrenal (HPA) system in depressed patients with
      and without PTSD. METHODS: Thirty-one depressed patients without PTSD, 12
      depressed patients with PTSD, and 23 healthy volunteers were studied on 2 days.
      Subjects received single-blind placebo on day 1 and fenfluramine on day 2.
      Cortisol levels were drawn before challenge and for 5 h thereafter. RESULTS:
      Cortisol levels increase with age in depressed patients without PTSD but not in
      depressed patients with PTSD or in healthy volunteers. Number of previous major
      depressive episodes was a predictor of the cortisol response to fenfluramine
      administration in depressed patients without PTSD. CONCLUSIONS: The results of
      our study highlight the importance of considering age in psychobiology. Further
      research is needed to fully delineate the role of age in abnormalities of the HPA
      axis found in major depression and PTSD.

PMID- 15465577
TI  - A dual vulnerability hypothesis for seasonal depression is supported by the
      seasonal pattern assessment questionnaire in relation to the temperament and
      character inventory of personality in a general population.
AB  - BACKGROUND: Personality structure obtained from the psychobiological Temperament
      and Character Inventory (TCI) was studied in relation to self-reported seasonal
      variations in mood and behavior measured by the Seasonal Pattern Assessment
      Questionnaire (SPAQ). METHODS: The subjects comprised 1761 adults (57.6% women)
      in the age range 35-85 years, enrolled in the Betula prospective random cohort
      study of Umea, Sweden. RESULTS: Personality profiles of subjects who reported the
      occurrence of a high degree of seasonal variation as such were associated with a
      combination of high self-transcendence (ST) and high persistence (PS),
      irrespective of the level of harm avoidance (HA). Subjects who reported feeling
      worst in winter were associated with high HA, irrespective of the levels of ST
      and PS. Also, subjects feeling worst in summer or experiencing overall problems
      with seasonal variation were associated with high HA in their personality
      profiles. Using the SPAQ criteria to define seasonal affective disorder (SAD) or
      subsyndromal SAD (S-SAD), subjects with these disorders often had combinations of
      high self-transcendence (ST) and high persistence (PS), but with different
      associations with HA. LIMITATIONS: No evaluations were made for SAD or
      subsyndromal SAD according to the DSM-IV or ICD 10 criteria. CONCLUSIONS: Our
      results relating SPAQ with TCI give support for a dual vulnerability hypothesis
      for seasonal depression proposed in the literature, where it is attributed to a
      combination of a seasonal factor and a depression factor. Examining the
      literature regarding the relationships between the different TCI scales and
      monoamine neurotransmitter functions, those relationships suggest that these two
      vulnerability factors for seasonal depression may be modulated by different
      neurotransmitter systems.

PMID- 15465578
TI  - Motor cortical excitability and clinical response to rTMS in depression.
AB  - BACKGROUND: The relationship between frontal lobe activity in the left and right
      hemispheres and the pathophysiology of depression remains unclear. In addition,
      it is uncertain whether levels of frontal or motor cortical excitability relate
      to clinical response to treatment modalities. We aimed to explore whether motor
      cortical excitability as assessed with single and paired pulse transcranial
      magnetic stimulation (TMS) could be used to predict the response to treatment
      with repetitive TMS (rTMS) applied to the left or right prefrontal cortex.
      METHODS: Motor thresholds, cortical excitability and cortical inhibition (CI)
      were assessed prior to a trial of rTMS in patients with treatment resistant
      depression. RESULTS: There was no consistent pattern of differences in
      hemispheric activity, although there was a relationship between the degree of
      psychopathology and cortical excitability (right hemisphere) and an inverse
      relationship between inhibitory activity and clinical response (left hemisphere).
      CONCLUSIONS: The study does not support a simple model of laterality in motor
      cortical excitability in depression. The TMS measures used in this study appear
      to be of limited use in the prediction of clinical response to rTMS.

PMID- 15465579
TI  - Use of prescription medications and complementary and alternative medicines to
      treat depressive and anxiety symptoms: results from a community sample.
AB  - BACKGROUND: Individuals prescribed antidepressants or anxiolytics may replace or
      augment such medications with complementary and alternative medicines (CAMs).
      Little is known about the extent to which individuals in the community use CAMs
      instead of, or in addition to, medications they have been prescribed, for anxiety
      and depressive symptoms. METHOD: Information on use of CAMs, antidepressants and
      anxiolytics was obtained from a community sample of 7485 survey participants from
      Canberra and environs, Australia. Participants aged 20-24, 40-44, or 60-64 were
      also provided information on sociodemographic attributes, physical and mental
      health. RESULTS: 6.29% of participants used only prescription medications to
      treat their depression or anxiety. 2.28% used only CAMs for this purpose while a
      further 0.59% reported using both types of treatments. Those using CAMs and those
      who took prescription medications had comparable levels of mental health problems
      while CAM users had fewer physical health problems and lower neuroticism.
      Compared with those taking neither CAMs nor prescribed medication, however, CAM
      users had more depressive and anxiety symptoms, worse mental health, higher
      neuroticism and lower levels of mastery. LIMITATIONS: Information on use of
      prescribed and CAMs is self-reported and is subject to the inaccuracies and
      omissions associated with this method of data collection. CONCLUSION: We found
      survey participants used CAMs less frequently than prescription medications to
      treat their depressive or anxiety symptoms. Nonetheless, medical practitioners
      should be aware that their patients may use CAMs and seek information about such
      use to reduce the likelihood of adverse interactions between prescribed
      medication and CAMs.

PMID- 15465580
TI  - Prefrontal hemodynamic response to verbal-fluency task and hyperventilation in
      bipolar disorder measured by multi-channel near-infrared spectroscopy.
AB  - BACKGROUND: Many neuroimaging studies of patients with bipolar disorder have
      demonstrated functional hypofrontality (reduced activation of the frontal
      cortex), although this finding is still controversial. We previously found
      hypoactivation of the left prefrontal region in remitted subjects with bipolar
      disorder measured by one-channel near-infrared spectroscopy (NIRS). The aim of
      the present study was to clarify whether or not this finding was due to altered
      cerebral lateralization or caused by reduced cerebrovascular reactivity. METHODS:
      We enrolled nine remitted patients with bipolar disorder and nine normal
      controls. Hemodynamic responses in the prefrontal cortex during the verbal
      fluency and hyperventilation tasks were monitored by 24-channel NIRS, which can
      measure oxygenated hemoglobin (OxyHb), deoxygenated hemoglobin, and total
      hemoglobin (TotalHb). RESULTS: The increases of OxyHb and TotalHb in the bipolar
      group were significantly smaller than that in the controls during the verbal
      fluency task. The response of TotalHb during hyperventilation in the bipolar
      group was weaker than that in the controls. LIMITATIONS: The sample size was
      small. CONCLUSIONS: These findings suggest that the bilateral hypofrontality to a
      cognitive task is seen in remitted subjects with bipolar disorder, which may be
      related to vascular function as measured by the response to hyperventilation.

PMID- 15465581
TI  - A prevalence study of antenatal depression among Chinese women.
AB  - BACKGROUND: There has thus far been no empirical research on the occurrence of
      antenatal psychiatric morbidity in Chinese population. Epidemiological studies in
      western societies generally show that depressive episodes occur in 10-20% of
      pregnant women. Longitudinal studies have demonstrated that antenatal depression
      is one of the most powerful predictors of postnatal depression. There is also a
      growing literature that shows that antenatal psychological distress can adversely
      affect maternal and foetal well being. METHODS: At 38 weeks of pregnancy, 238
      consecutive women were invited to return for psychiatric assessment. The
      participants were interviewed using the non-patient version of the Structured
      Clinical Interview for DSM-IV (SCID-NP). RESULTS: Seventy women (29%) declined to
      participate, and another 11 (5%) defaulted the SCID interview. Among the 157
      women interviewed, the 1-month prevalence of antenatal depression was 4.4%. The 1
      month prevalence of all psychiatric diagnoses was 6.4%. The prevalence of
      antenatal depression and all psychiatric diagnoses for the entire pregnancy was
      6.4% and 8.3%, respectively. LIMITATIONS: About a third of eligible subjects did
      not participate in the study. CONCLUSIONS: A significant proportion of Chinese
      women suffer from psychiatric morbidity during pregnancy. Depressive disorders
      are by far the commonest morbidity in the study population. Given the scope of
      the morbidity and the potential impact on obstetric and neonatal outcomes, early
      screening and treatment are warranted.

PMID- 15465582
TI  - Accounting for depressive symptoms in women: a twin study of associations with
      interpersonal relationships.
AB  - BACKGROUND: This study examined how interpersonal relationships, specifically
      marital quality and adequacy of social support, are associated with depressive
      symptoms among women. METHODS: A sample of 326 female monozygotic and dizygotic
      twin pairs and their spouses was drawn from the Swedish Twin Registry.
      Associations among the three variables were evaluated by comparing similarities
      among monozygotic and dizygotic female twin pairs. RESULTS: Interpersonal
      relationships contributed between 18% and 31% of the variance for depressive
      symptoms in women. Associations among the three variables were accounted for by
      genetic influences when women's reports were used. Non-shared environmental
      influences were important for the association between marital quality and
      depressive symptoms when a combination of husband and wife reports of marital
      quality were used. LIMITATIONS: The data is cross-sectional and the
      generalizability of these findings to depressive symptoms in men or to
      individuals with major depression is not clear. CONCLUSIONS: These findings
      indicate important associations among marital quality, social support and
      depressive symptoms in women, which should be taken into consideration for
      prevention and intervention strategies targeting depression.

PMID- 15465584
TI  - Comorbid major depression and panic disorder: significance of temporal sequencing
      to familial transmission.
AB  - BACKGROUND: Panic disorder (PD) and major depression frequently coexist but the
      nature of the relationship is controversial. Our aim was to determine if the risk
      for depression in a proband is influenced by the temporal sequence of comorbid PD
      and major depression in an affected family member. METHODS: Of participants in a
      larger study of individuals who had a family, but no personal history of PD, 31
      had a first-degree relative with comorbid PD and major depressive disorder (MDD).
      In 16, the onset of MDD preceded PD (HR-MDPD), and in 15, PD was established
      before the first depressive episode (HR-PDMD). Thirty-seven low-risk controls
      (LRC) described no first-degree relatives with psychiatric illness. Participants
      were assessed using the SADS-LA and provided family history data on first-degree
      relatives. RESULTS: High-risk subjects whose first-degree relative had temporally
      primary depression had a 50% chance of having had a major depressive episode.
      Those with a first-degree relative with primary panic and secondary depression
      were at no greater risk of having had a depression than were normal controls
      (6.7% and 5.4%, respectively). LIMITATIONS: The use of the family history method
      has the intrinsic weakness of relying solely on proband knowledge. CONCLUSION:
      The temporal relationship between comorbid panic and depression may play an
      important role in determining the familial risk for depression in family members.

PMID- 15465583
TI  - Does a U-shaped relationship exist between alcohol use and DSM-III-R mood and
      anxiety disorders?
AB  - BACKGROUND: In recent community surveys, abstainers and heavy drinkers of alcohol
      have reported more mood and anxiety symptoms than moderate drinkers (U-shaped
      relationship). The present study was aimed at extending this finding by
      investigating this potential U-shaped relationship using structured diagnostic
      interviews to assess mood and anxiety disorders. METHODS: Data came from two
      contemporaneous surveys, the National Comorbidity Survey (NCS; N=6780) and the
      Mental Health Supplement of the Ontario Health Survey (OHS-MHS; N=7001). The
      University of Michigan Revision of the Composite International Diagnostic
      Interview (UM-CIDI) was used to make DSM-III-R psychiatric diagnoses in both
      surveys. Three mutually exclusive lifetime alcohol use categories were compared:
      (1) Alcohol abstainers-individuals reporting no alcohol use or less than 12
      drinks in any year throughout their life. (2) Moderate drinkers-individuals that
      did not meet criteria for alcohol abstainers or problem drinkers. (3) Problem
      drinkers-DSM-III-R lifetime alcohol abuse, dependence or hazardous levels of
      alcohol use. RESULTS: After controlling for demographic variables, alcohol
      abstainers were not found to have significantly higher rates of mood and anxiety
      disorders in comparison with moderate drinkers. However, problem drinking was
      significantly associated with mood and anxiety disorders. CONCLUSIONS: Across
      both surveys, there was no evidence of a U-shaped relationship between lifetime
      alcohol consumption and lifetime mood and anxiety disorders.

PMID- 15465585
TI  - "Coping with depression": an open study of the efficacy of a group
      psychoeducational intervention in chronic, treatment-refractory depression.
AB  - BACKGROUND: Failure to respond to antidepressant medication represents a major
      clinical problem. Few therapeutic interventions have been shown to benefit such
      individuals. METHOD: Patients attended a 12-session psychoeducational programme
      over a period of 10 weeks, with follow-up at 26 weeks. The main outcome measures
      were the self-report Beck Depression Inventory (BDI-II), the Global Severity
      Index (GSI) of the Brief Symptom Inventory (BSI) and the EuroQol 5D. RESULTS:
      Baseline assessments confirmed substantial chronicity and treatment resistance,
      high symptom burden and poor quality of life in the study cohort. Twenty-six week
      follow-up data were obtained from 34% of cohort. Completion of the course was
      associated with clinically significant changes in symptom burden. Sustained
      remission was achieved by 35% of completers. LIMITATIONS: We did not characterise
      the cohort using structured clinical interview and did not collect structured,
      objective ratings of mental health status. There was no control group. There was
      a high attrition rate and caution must be exercised in interpreting results.
      CONCLUSIONS: For a proportion of patients with chronic depressive episodes that
      have not responded to antidepressant treatments, the "Coping with Depression"
      psychoeducational group may confer sustained and meaningful benefit. Controlled
      studies are warranted.

PMID- 15465586
TI  - Bipolar disorder: I. Temperament and character.
AB  - BACKGROUND: The nature of the relationship between personality and bipolar
      affective disorders is an important but unanswered question. METHODS: We have
      studied personality in bipolar patients by using the Temperament and Character
      Inventory (TCI). TCI were administered to 100 euthymic bipolar patients and 100
      controls from the normal population. RESULTS: Bipolar patients were significantly
      higher in harm avoidance (HA) and lower in reward dependence (RD), self
      directedness (SD), and cooperativeness (CO) than controls. Bipolar patients are
      more fatigable, less sentimental, more independent, less purposeful, less
      resourceful, less empathic, less helpful, less pure-hearted, and have less
      impulse control than controls. Bipolar II patients are more impulsive, more
      fatigable, less resourceful, and have less impulse control than bipolar I
      patients. LIMITATIONS: Our results are limited to euthymic bipolar patients and
      cannot be generalized to affective disorders. CONCLUSIONS: Even when clinically
      euthymic on lithium maintenance, bipolar patients continue to have a
      characteristic cognitive deficit. This is in agreement with cognitive theories
      about cognitive deficits in depression that are regarded as important
      vulnerability factors in mood disorders.

PMID- 15465587
TI  - Styles of adaptation in autoimmune thyroiditis and bipolar disorder: a pilot
      study.
AB  - BACKGROUND: A growing body of evidence suggests that styles of adaptation,
      assessed with the Serial Color-Word Test (S-CWT, a 5-trials Stroop task), are
      able to differentiate several mental and psychosomatic disorders. Recent findings
      have confirmed a very high rate of cases of autoimmune thyroiditis (so called
      Hashimoto disease) among bipolar patients, suggesting an etio-pathogenetic
      relatedness between the two ailments. Based on the latter relatedness, it was
      hypothesized that the same styles of adaptation, which are known to differentiate
      bipolar and control subjects are also characteristic of patients with autoimmune
      thyroiditis. METHODS: Three groups (autoimmune thyroiditis, fully remitted
      bipolar I, and nonclinical) of 40 women, matched on age and schooling, were
      administered the S-CWT. The following variables were considered: (a) early
      discontinuity (i.e. the summed nonlinear change of the first three trials), (b)
      late discontinuity (i.e. the summed nonlinear change of the last two trials), (c)
      across-trials discontinuity (i.e. the nonlinear change of the five measures of
      nonlinear change). RESULTS: The thyroiditis group had (1) higher values of early
      discontinuity (P=0.006) and of late discontinuity (P=0.004) compared with
      nonclinical controls, (2) lower values of early discontinuity (P=0.005) and of
      across-trials discontinuity (P=0.008) compared with the bipolar group.
      LIMITATIONS: The study did not include men patients and lacked a quantification
      of affective symptoms among clinical and nonclinical participants. CONCLUSION: A
      discontinuous style of adaptation is more marked among remitted bipolar than
      among thyroiditis patients, and more marked among the latter ones than among
      nonclinical controls, thus delineating a sort of adaptive continuum.

PMID- 15465588
TI  - Mood disorders in opioid-dependent patients.
AB  - AIMS: To assess the rate of current mood disorders in opioid-dependent
      outpatients. DESIGN: Prevalence study of DSM-IV mood disorders. SETTINGS: Private
      and government clinics. PARTICIPANTS: Five hundred unpaid opioid-dependent
      patients who had voluntarily sought treatment. MEASUREMENTS: The Research version
      of structured clinical interview for DSM-IV Axis I Disorders (SCID-I). RESULTS:
      The mean age of the subjects (487 men and 13 women) was 33.4 years, ranging from
      16 to 67. The majority (68.2%) had private sector job and 13.4% were unemployed.
      The majority (59.8%) had education at the level of primary, guidance or high
      school and only 3.8% were illiterate. Three hundred and thirty six (67.2%)
      subjects were diagnosed as having mood disorders. Of the subjects 274 (54.8%) had
      substance induced depression, 37 (7.4%) major depression, 14 (2.8%) dysthymia,
      five (1%) depression due to general medical condition, three (0.6%) cylothymia,
      three (0.6%) bipolar mood disorder type I. None was diagnosed as having bipolar
      mood disorder type II. Of the participants 319 (63.8%) reported more than 5 years
      use of opioid. Of the subjects only 16 (3.2%) reported no episode of abstinence
      and the majority 484 (96.8%) reported one or more episodes of abstinences. About
      4.2% (21) reported less than 1 g/day and the majority 86.4% (432) reported
      between 1 and 5 g/day current use of opioid. CONCLUSION: Due to high rates of
      mood disorders in opioid-dependent subjects, psychiatric services should be open
      and accessible to the patients, especially those who voluntarily seek help and
      treatment.

PMID- 15465589
TI  - Effects of stress and social support on recurrence in bipolar disorder.
AB  - BACKGROUND: Limited research has examined the impact of social support on the
      course of bipolar disorder, although results suggest a probable link. This study
      examines prospectively the effects of stressful events and social support on
      episode recurrence in bipolar I disorder. METHODS: Fifty-two outpatients with
      bipolar I disorder recruited from an urban community were followed every 3 months
      for up to 1 year. At the initial interview, individuals reported separately on
      perceived social support from a best friend, parent, and romantic partner,
      combined to form a total network support score. Ongoing prospective assessments
      of stressful life events, symptomatology, and medication compliance were
      completed over 1 year. Logistic regressions were utilized to predict episode
      recurrence. RESULTS: As predicted, both higher levels of stress and lower levels
      of social support from the total network independently predicted depressive
      recurrence over a 1-year follow-up, after controlling for clinical history and
      compliance. Social support did not moderate the impact of stress. LIMITATIONS:
      Only a 1-year follow-up was obtained, and sample sizes may have been insufficient
      to detect prediction of manic episodes. Direction of causality between support
      and recurrence is hypothesized but cannot be definitively determined.
      CONCLUSIONS: Higher levels of stress and perceptions of less available and poorer
      quality close relationships are associated with recurrence. Interventions that
      target these psychosocial vulnerabilities may help alter the course of bipolar I
      disorder. Research with larger samples should further examine the possible
      polarity-specific effects of social risk factors.

PMID- 15465590
TI  - Treatment-emergent mania in pediatric bipolar disorder: a retrospective case
      review.
AB  - BACKGROUND: Pediatric bipolar disorder (BPD) can be misdiagnosed as a depressive,
      attention, conduct, or anxiety disorder and treatment with antidepressants and
      stimulants is common. Risk of adverse outcomes related to such treatment remains
      poorly defined. METHODS: We analyzed clinical records of 82 children (mean age
      10.6 years) meeting modified DSM-IV diagnostic criteria for BPD to evaluate risk
      and timing of operationally-defined treatment-emergent mania (TEM) or increased
      mood-cycling following pharmacological treatment. RESULTS: Of 82 juvenile BPD
      patients, 57 (69%) had been given a mood-elevating agent at least once; 33/57
      (58%) so-exposed met criteria for TEM, with median latency of 14 days; TEM was
      observed twice as often with antidepressants as stimulants (44% vs. 18%). TEM led
      to first-recognition of BPD in 14 cases (17%), and some drug-exposed children (4
      9%) had prominent suicidal, homicidal or psychotic behavior. In addition to
      recent exposure to a mood-elevating agent, TEM was associated with early-onset
      anxiety and female gender. LIMITATIONS: Findings are retrospective in clinically
      diagnosed and treated outpatients, but involved otherwise unselected cases of
      juvenile BPD. CONCLUSIONS: TEM was reported in 58% of children with probable
      juvenile BPD within several weeks of new exposure to a mood-elevating agent.

PMID- 15465591
TI  - Laquinimod (ABR-215062) suppresses the development of experimental autoimmune
      encephalomyelitis, modulates the Th1/Th2 balance and induces the Th3 cytokine TGF
      beta in Lewis rats.
AB  - The new orally active drug laquinimod (ABR-215062) was evaluated in experimental
      autoimmune encephalomyelitis (EAE) in the Lewis rat. EAE shares important
      immunological and clinical features with multiple sclerosis (MS). Doses of 16,
      1.6 and 0.16 mg/kg/day laquinimod dose-dependently inhibited disease and showed
      better disease inhibitory effects as compared to roquinimex (Linomide).
      Furthermore, laquinimod inhibited the inflammation of both CD4+ T cells and
      macrophages into central nervous tissues, i.e. the spinal cord. It also changed
      the cytokine balance in favour of TH2/TH3 cytokines IL-4, IL-10 and TGF-beta.
      Laquinimod therefore represents a new orally active immunoregulatory drug without
      general immunosuppressive properties with a potential for the treatment of severe
      autoimmune diseases like MS.

PMID- 15465592
TI  - Mimotopes of conformational epitopes in fibrillar beta-amyloid.
AB  - In Alzheimer's disease (AD) beta-amyloid peptide accumulates in the brain in
      different forms including fibrils. Amyloid fibrils could be recognized as foreign
      by the mature immune system since they are not present during its development.
      Thus, using mouse antisera raised against the fibrillar form of Abeta42, we have
      screened two phage peptide libraries for the presence of foreign conformational
      mimotopes of Abeta. Antisera from wild type animals recognized predominately
      peptides with the EFRH motif from Abeta42 sequence, whereas amyloid precursor
      protein (APP) transgenic mice recognized mainly phage clones that mimic epitopes
      (mimotopes) within the fibrillar Abeta42 but lack sequence homology with this
      peptide.

PMID- 15465593
TI  - Stress causes a further decrease in immunity to herpes simplex virus-1 in
      immunocompromised hosts.
AB  - Physical or psychological stress can modulate immune responses in normal
      subjects. The effects of stress on immunity in immunocompromised hosts, however,
      have not been extensively investigated. Here we assess relationships among
      footshock stress (FS), infection with herpes simplex virus-1 (HSV-1), and
      immunosuppression by cyclophosphamide (CY) during the active immune response to
      virus in BALB/c mice. Without FS, CY significantly decreased survival and body
      weight gain, splenic leukocyte numbers, in vivo serum cytokine level and in vitro
      splenocyte cytokine production during HSV-1 infection. FS alone also
      significantly inhibited cell mediated anti-viral responses to HSV-1. However, FS
      in combination with certain CY doses led to a further significant decrease in
      host responses compared to either CY or FS treatment alone, including decreased
      survival rate, increased weight loss, lowered leukocyte numbers, reduced cytokine
      production in vivo and in vitro, and decreased numbers of cytokine-producing
      cells (IL-12 and IFNgamma). In contrast, CY, but not FS, significantly reduced in
      vivo anti-HSV-1 antibody secretion. These data support the hypothesis that stress
      can further reduce host immune responses in immunocompromised individuals. Thus,
      stress levels of patients should be taken into consideration prior to clinical
      treatment with immunosuppressants.

PMID- 15465594
TI  - Overproduction of corticotropin-releasing hormone blocks germinal center
      formation: role of corticosterone and impaired follicular dendritic cell
      networks.
AB  - Corticotropin-releasing hormone (CRH) is a central mediator in the response to
      stress, coordinating behavioral, autonomic and neuroendocrine activation. CRH
      overproduction is implicated in several affective disorders, including major
      depression, panic-anxiety disorder and anorexia--diseases also associated with
      altered immune function. We investigated the link between CRH overdrive and
      immune function using CRH transgenic mice. Following immunization, CRH transgenic
      mice fail to form germinal centers; chronic glucocorticoid administration
      recapitulates this effect in wild-type mice. Regulation of germinal centers by
      glucocorticoids appears to be mediated, in part, through effects on follicular
      dendritic cells (FDC), providing a novel mechanism by which CRH dysregulation may
      significantly impair humoral immune responses.

PMID- 15465595
TI  - A monoclonal antibody to CD11d reduces the inflammatory infiltrate into the
      injured spinal cord: a potential neuroprotective treatment.
AB  - The accumulation of inflammatory cells in the lesion of a spinal cord injury
      (SCI) enhances secondary damage, resulting in further neurological impairment.
      High-dose methylprednisolone (MP) treatment is the only accepted treatment for
      inflammation secondary to human SCI but is minimally effective. Using a rat SCI
      model, we devised an anti-inflammatory treatment to block the infiltration of
      neutrophils and hematogenous monocyte/macrophages over the first 2 days
      postinjury by targeting the CD11dCD18 integrin. Anti-CD11d mAb administration
      following SCI effectively reduced neutrophil and macrophage infiltrate into
      lesions by 70% and 36%, respectively, over the first 72 h post-SCI. MP also
      reduced neutrophil and macrophage infiltrate by 60% and 28%, respectively, but by
      different mechanisms. The immunosuppression caused by anti-CD11d treatment was
      not sustained, as inflammatory cell numbers were not different from those
      observed in untreated SCI control animals at 7 days postinjury. In contrast, in
      MP-treated animals, the number of macrophages was still suppressed in the lesion
      while neutrophil numbers were significantly increased. These results suggest that
      anti-CD11d mAb treatment following SCI will minimize the destructive actions
      associated with early, uncontrolled leukocyte infiltration into the lesion while
      permitting the positive wound healing effects of macrophages at later time
      points.

PMID- 15465596
TI  - Dendritic cells exposed to estrogen in vitro exhibit therapeutic effects in
      ongoing experimental allergic encephalomyelitis.
AB  - Immunomodulatory effects of estrogen have been demonstrated by clinical and
      experimental observations, but the mechanisms by which estrogen exhibits the
      effects remain to be defined. One possible mechanism by which estrogen inhibits
      the development of experimental allergic encephalomyelitis (EAE), a commonly used
      model of multiple sclerosis (MS) in humans, is over the functions of dendritic
      cells (DC). Here, we describe that splenic DC from Lewis rats obtained on day 12
      post-immunization (p.i.) with myelin basic protein (MBP) encephalitogenic peptide
      68-86+Freund's complete adjuvant (FCA), after being exposed in vitro 17beta
      estradiol, exhibited therapeutic effects on acute EAE when injected
      subcutaneously on day 5 p.i. Blood mononuclear cells (MNC) were isolated from
      thus treated rats on day 12 p.i. Administration of estrogen-exposed DC prevented
      the expansion of CD4+ T cells and increased proportions of regulatory T cells
      producing IL-10 and CD4+CD28- suppressor T cells, accompanied with increased IL
      10 and IFN-gamma, and reduced TNF-alpha production. Infiltrates of CD68+
      macrophages within the central nervous system and MBP 68-86-induced T cell
      proliferation were inhibited in rats injected with estrogen-exposed DC compared
      to rats injected with naive DC. Estrogen up-regulated the expression of
      indoleamine 2,3-dioxygenase, which promotes tolerogenic properties of DC. The
      results suggest that in vitro exposure of DC to estrogen modulates DC functions
      and results in a therapeutic effect of DC.

PMID- 15465597
TI  - Twenty-four-hour rhythms of mitogenic responses, lymphocyte subset populations
      and amino acid content in submaxillary lymph nodes of growing male rats subjected
      to calorie restriction.
AB  - Peripubertal male Wistar rats were submitted to a calorie restriction diet
      enriched in proteins and low in fat and carbohydrates for 4 weeks, and starting
      on day 35 of life. Mitogenic responses, lymphocyte subset populations, interferon
      (IFN)- gamma release and amino acid content were determined in submaxillary lymph
      nodes at six time intervals during the 24-h span. The diet employed completely
      arrested growth in growing rats. After caloric restriction, mean values of Con A
      response, lymph node T and CD4+ cell number and CD4+/CD8+ ratio augmented,
      whereas those of B cell number, IFN-gamma release and glutamine and glutamate
      concentration decreased. Calorie restriction modified 24-h rhythmicity of lymph
      node mitogenic responses to Con A and LPS, and of T, T-B, CD4+ and CD4+ -CD8+
      lymph node cell subsets. It also changed the 24-h pattern of lymph node IFN-gamma
      release and glutamine, aspartate, glutamate and taurine lymph node content.
      Availability of nutrients presumably affects the mechanisms that modulate the
      circadian variation of immune responsiveness in growing rats.

PMID- 15465598
TI  - The chemokine CXCL10 modulates excitatory activity and intracellular calcium
      signaling in cultured hippocampal neurons.
AB  - In this study, we provide evidence for direct modulatory effects of the
      chemokine, CXCL10, on the physiology of hippocampal neurons maintained in primary
      culture. CXCL10 elicited a rise in intracellular Ca2+ and enhanced both
      spontaneous and evoked electrical activity of hippocampal neurons. CXCL10-induced
      elevations in intracellular Ca2+ were associated with an increase in neuronal
      firing and an alteration in the relationship between the evoked Ca2+ signal and
      neuronal activity. The effects of CXCL10 were not accompanied by a shift in
      resting membrane potential (RMP) or input resistance. Expression of the CXCR3
      chemokine receptor supports a direct effect of CXCL10 on hippocampal neurons.

PMID- 15465599
TI  - Ethanol selectively modulates inflammatory activation signaling of brain
      microglia.
AB  - In spite of well-known deleterious effects of alcohol on the nervous system in
      general, its specific effect on the brain immune system remains poorly
      understood. In order to better understand the effect of alcohol consumption on
      the innate immunity and inflammatory responses in the central nervous system
      (CNS), we sought to determine how ethanol influences inflammatory activation of
      microglia that function as the resident immune defense system of the brain. After
      treatment of BV-2 mouse microglial cells or rat primary microglia cultures with
      various stimuli, nitric oxide (NO) production was measured as an indicator of
      microglial activation. Pretreatment of the cells with ethanol (10-100 mM) for 1 h
      resulted in a significant decrease in lipopolysaccharide (LPS)-induced, but not
      interferon-gamma (IFNgamma)-induced, NO production, indicating that ethanol
      specifically inhibits LPS-induced inflammatory activation of microglia. This was
      further supported by the ethanol inhibition of LPS-induced IL-1beta expression.
      In addition, ethanol pretreatment selectively regulated LPS-induced NF-kappaB
      signaling pathway without affecting IFNgamma-induced signal transducer and
      activator of transcription 1 (STAT1) phosphorylation, interferon regulatory
      factor-1 (IRF-1) induction or IFNgamma-inducible IP-10 expression. The modulation
      of LPS-induced NF-kappaB by ethanol was due to the inhibition of coactivator
      p300. Altogether, these results suggest that acute ethanol exposure may
      selectively modulate signal transduction pathways associated with inflammatory
      activation of microglia, which may lead to derangement of CNS immune and
      inflammatory responses.

PMID- 15465600
TI  - Activation thresholds determine susceptibility to peptide-induced tolerance in a
      heterogeneous myelin-reactive T cell repertoire.
AB  - Altered peptide ligands (APL) with increased MHC-binding properties are highly
      effective at inducing T cell tolerance after systemic administration in soluble
      form, preventing experimental autoimmune encephalomyelitis (EAE) induced with the
      myelin basic protein (MBP) Ac1-9 peptide. We have previously described a diverse
      Ac1-9-reactive T cell repertoire with differing TCR affinities. A remaining
      question is what proportion of this repertoire is silenced by peptide therapy?
      Here, we show that the sensitivity of a T cell to peptide-induced tolerance is
      related to its avidity for native Ac1-9. These data provide new evidence that
      self-reactive T cells bearing low-affinity TCRs are able to escape therapeutic
      induction of tolerance.

PMID- 15465601
TI  - Fever of recombinant human interferon-alpha is mediated by opioid domain
      interaction with opioid receptor inducing prostaglandin E2.
AB  - We have reported that there are distinct domains in Interferon-alpha (IFNalpha)
      molecule mediating immune and opioid-like effects respectively. And the opioid
      effect of IFNalpha is mediated by mu opioid receptor. We report here the
      structural basis of fever induced by recombinant human IFNalpha. Two kinds of
      IFNalpha mutants were obtained and used to investigate the structural basis of
      fever of IFNalpha, which are 129Ser-IFNalpha and 38Leu-IFNalpha. The antiviral
      activity of 129Ser-IFNalpha almost disappeared, but there still retained the
      strong analgesic activity. The antiviral activity of 38Leu-IFNalpha remained, but
      the analgesic activity disappeared completely. It showed that IFNalpha and 129Ser
      IFNalpha decreased cAMP production, induced the fever, and stimulated PGE2 to
      release from the hypothalamus slices, which could be blocked by naloxone, but
      38Leu-IFNalpha failed. It is the first demonstration that fever induced by
      IFNalpha is mediated by opioid domain of IFNalpha interacting with opioid
      receptor. It is inferred that high-activity and low side-effect IFNalpha or other
      cytokines could be obtained after being changed the motifs in the tertiary
      structure.

PMID- 15465602
TI  - Differential effects of interferon-gamma on the expression of cyclooxygenase-2 in
      high-grade human gliomas versus primary astrocytes.
AB  - We compared effects of interferon-gamma (IFNgamma) on cyclooxygenase-2 (COX-2)
      expression in malignant human glioma cell lines and cultured primary human
      astrocytes. While IFNgamma inhibited interleukin-1beta (IL1beta)-induced
      expression of COX-2 in the glioma cells, it enhanced expression in primary
      astrocytes. This differential effect correlated with the observed modulation of
      NFkappaB and AP-1 DNA binding activity; reduced in the glioma cells, increased in
      primary astrocytes. Furthermore, IFNgamma had a significantly greater anti
      proliferative effect on the glioma cells than COX inhibitors. This inhibitory
      effect of IFNgamma on expression of COX-2 in human glioma cells may have
      relevance for immunotherapies directed against high-grade gliomas.

PMID- 15465603
TI  - Early administration of IL-12 suppresses EAE through induction of interferon
      gamma.
AB  - Recent findings have shown that IL-12, a key inducer of Th1 cell development, is
      not required in the pathogenesis of experimental autoimmune encephalomyelitis
      (EAE) as severe CNS inflammatory demyelination can develop in the absence of IL
      12 or IL-12 responsiveness. These data raised the possibility of an
      immunomodulatory action of IL-12 in this disease model. We show here that IL-12
      suppresses MOG35-55-induced EAE in the C57BL/6 mouse when administered during the
      early induction phase of the disease. The inhibitory effect is interferon-gamma
      (IFN-gamma)-dependent, as clearly shown by lack of suppression in IFN-gamma
      deficient mice, and is also accompanied by inhibition of mRNA expression of the
      proinflammatory cytokine IL-17.

PMID- 15465604
TI  - B7.2 on activated and phagocytic microglia in the facial axotomy model:
      regulation by interleukin-1 receptor type 1, tumor necrosis factor receptors 1
      and 2 and endotoxin.
AB  - Co-stimulatory factors are involved in different forms of brain pathology and
      play an important role in the activation of T-cells. In the current study, we
      explored the regulation of B7.2, a prominent member of the B7 family of
      costimulatory factors, in the facial motor nucleus (FMN) following facial axotomy
      and systemic application of lipopolysaccharide (LPS, endotoxin) using light and
      electron immunohistochemistry and cytokine-receptor-deficient mice. Facial
      axotomy led to a gradual increase of B7.2 immunoreactivity (IR) on microglial
      cell surface; similar effects were also observed following application of LPS,
      but both effects were not additive, suggesting overlapping or saturated signaling
      pathways. Some B7.2-IR was already present on activated microglia surrounding
      injured neurons at days 1-4 after injury, but became particularly intense during
      neuronal cell death, peaking at day 14. Previous studies revealed that these late
      microglial changes are accompanied by a strong increase in the expression of
      proinflammatory cytokines such as interleukin-1 beta (IL1beta) tumor necrosis
      factor-alpha (TNFalpha) and interferon gamma (IFNgamma) [J. Neurosci. 18 (1998a)
      5804]. Here, deletion of the receptors for these cytokines-IL1R1, TNFR1 or TNFR2,
      but not IFNgammaR1-caused a strong and significant reduction in B7.2-IR in
      reactive microglial cells, compared with their wild type (WT) controls on the
      same genetic strain background, with a 31% decrease in IL1R1-/- , 39% in TNFR1-/-
      and 49% in TNFR2-/- mice. These data underscore the significance of IL1beta,
      TNFalpha and LPS, and their receptors, as potent inflammatory signals that
      regulate the cellular response in the injured brain as well as the interaction
      with the rapidly recruited immune system. The broad susceptibility of B7.2
      regulation to a wide range of different inflammatory signals also points to its
      role as a sensor of molecular pathology, and a factor that plays an important
      accessory role in allowing and shaping the microglia/T-cell interaction in the
      injured central nervous system.

PMID- 15465605
TI  - Neutrophils as a specific target for melatonin and kynuramines: effects on
      cytokine release.
AB  - A growing body of evidence suggests that the pineal hormone, melatonin, has
      immunomodulatory properties, although very little is known about its effect on
      leukocytes. Therefore, we aimed to investigate the effect of melatonin and its
      oxidation product N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) on cytokine
      production by neutrophils and peripheral blood mononuclear cells (PBMCs). AFMK
      (0.001-1 mM) inhibits the lipopolysaccharide (LPS)-mediated production of tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) more efficiently in
      neutrophils than PBMCs. Moreover, the inhibitory activity of AFMK is stronger
      than that of melatonin. Interestingly, monocytes efficiently oxidize melatonin to
      AFMK. We conclude that neutrophils are one of the main targets for melatonin and
      that at least part of the effects described for melatonin on immune cells may be
      due to its oxidation product, AFMK. We also consider that the oxidation of
      melatonin may be an important event in the cross-talking between neutrophils and
      monocytes.

PMID- 15465606
TI  - Effects of social stress on blood leukocyte distribution: the role of alpha- and
      beta-adrenergic mechanisms.
AB  - Social stress in mammals has repeatedly been shown to cause substantial
      alterations in the distribution pattern of immune cells in the peripheral blood.
      The studies described here investigated the role of adrenergic mechanisms in
      mediating stressor-induced changes in blood leukocyte numbers using a social
      confrontation procedure in the rat. Experimental manipulations were carried out
      to eliminate the stress-associated release of adrenal hormones or to block the
      binding of endogenous catecholamines to alpha- and beta-adrenergic receptors.
      Adrenalectomy completely abolished the stressor-induced decreases in circulating
      numbers of T helper cells (CD4+), cytotoxic T cells (CD8+) and B cells but was
      ineffective in preventing neutrophil granulocytosis, monocytosis and an increase
      in natural killer (NK) cells. Treatment with the alpha-adrenergic antagonist
      phentolamine (PHE) was highly effective in preventing granulocytosis and
      partially blocked lymphopenia, but failed to abolish monocytosis and an increase
      in NK cells. Treatment with the beta-adrenergic antagonists propranolol (PROP) or
      nadolol (NAD) entirely blocked the increases in monocytes and NK cells. In
      addition, beta-adrenergic blockade also significantly reduced neutrophilia, with
      PROP being more effective than NAD. The results presented here provide evidence
      that catecholamines play an important role in the redistribution of blood
      leukocytes during social stress. In particular, the mobilization of cells of the
      innate immune response seems to be regulated by adrenergic mechanisms.

PMID- 15465607
TI  - Dendritic cells activate autologous T cells and induce IL-4 and IL-10 production
      in myasthenia gravis.
AB  - Dendritic cells (DC), as initiators and orchestrators of immune responses,
      control both naive and primed T cell responses. Depending on their maturation
      stage, DC promote immunity or tolerance. Here we investigated (1) the phenotype
      and cytokine secretion patterns of IL-10-modulated immature DC (IL-10-DC) and
      lipopolysaccharide (LPS)-driven mature DC (LPS-DC) in comparison with unmodulated
      immature DC (imDC) and (2) the effects of IL-10-DC, and of LPS-DC, vs. imDC on
      autologous T cell responses in patients with myasthenia gravis (MG) compared with
      healthy controls (HC). All three types of DC derived from MG significantly
      increased the levels of CD4+CD25+ T cells and of their subfraction expressing
      CD69, when compared to DC derived from HC. IL-10-DC induced production of IL-10
      and IL-4 by T cells from MG patients, but only IL-10 production from HC. LPS-DC
      activated autologous T cells as reflected by augmented CD25, CD69 and CTLA-4
      expression on CD4+ T cells, without differences between MG and HC. This was
      associated with increased production of both Th1 (IFN-gamma) and Th2 (IL-10 and
      IL-4) cytokines by T cells. These results indicate that DC-induced activation of
      autologous T cells is more pronounced in MG than in HC. In addition, DC-induced T
      cell responses in MG vs. HC are more Th2-prone.

PMID- 15465608
TI  - The role of the polio virus receptor and the herpesvirus entry mediator B genes
      for the development of MS.
AB  - Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of
      the central nervous system (CNS). Although the cause of MS is still uncertain, it
      is well accepted that both genetic and environmental factors are important for
      the development of disease. In this study, we focused on the Polio Virus Receptor
      (PVR) and Herpesvirus entry mediator B (HVEB) receptor genes, which are located
      on chromosome 19q13, a region previously linked to MS. Both receptors are
      expressed in the brain and immune system and play an important role for inter
      cellular adhesion and entry of neurotropic viruses to the brain. We identified
      four new polymorphisms in the PVR gene, which were located in the promoter region
      and three different exons. All exonic polymorphisms altered the amino acid
      sequence of the receptor. No new polymorphisms were found in the HVEB gene, but
      we confirmed a previously identified intronic polymorphism. We analyzed the
      frequency of the polymorphisms by RFLP analysis in sporadic MS patients, MS
      families, and healthy controls and determined the surface expression of HVEB and
      PVR on peripheral blood monocytes. We did not find differences in the frequency
      of the polymorphisms or surface expression between MS patients and controls.
      Overall, our findings do not support a role of HVEB and PVR genes in the
      development of MS.

PMID- 15465609
TI  - Gangliosides act as onconeural antigens in paraneoplastic neuropathies.
AB  - We describe two patients with progressive neuropathy and lung cancer in whom
      gangliosides (GS) may represent the oncoantigens. Patient 1 had motor neuropathy,
      high titers of IgG1 and IgG3 to GD1a and GM1, and expansion of circulating gamma
      delta T lymphocytes, a T-cell subset responding to glycolipids. Patient 2
      presented with Miller-Fisher-like syndrome and IgG3 activity to disialo-GS. In
      both cases, decreased autoimmune responses and stabilization of neuropathy were
      accomplished by tumor treatment. By immunohistochemistry, patient 1's IgG bound
      to his own tumor and to structures of normal nervous system expressing GD1a or
      GM1. Infiltration of IgG in the same neural structures was found at his autopsy.
      Regarding cellular immunity, the proportion of gamma-delta T lymphocytes
      infiltrating carcinoma from patient 1 was significantly higher than in neoplastic
      controls. These results indicate that GS may represent onconeural antigens in
      paraneoplastic neuropathy (PNN); their expression on neoplastic tissue may elicit
      autoimmune responses, which also target neural structures.

PMID- 15465610
TI  - Longer dinucleotide repeat polymorphism in matrix metalloproteinase-9 (MMP-9)
      gene promoter which correlates with higher HTLV-I Tax mediated transcriptional
      activity influences the risk of HTLV-I associated myelopathy/tropical spastic
      paraparesis (HAM/TSP).
AB  - Matrix metalloproteinase-9 (MMP-9) has been reported to be expressed in various
      inflammatory disorders including human T cell lymphotropic virus type I (HTLV-I)
      associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-I-infected T
      cells expressed high levels of MMP-9 via viral transactivator Tax mediated
      activation of the MMP-9 promoter. To investigate whether the d(CA) repeat
      polymorphism in MMP-9 promoter affects the risk of developing HAM/TSP, we
      compared the allele frequencies between 200 HAM/TSP patients and 200 HTLV-I
      seropositive asymptomatic carriers (HCs). The longer d(CA) repeat alleles of MMP
      9 promoter, which was associated with higher Tax-mediated transcriptional
      activity, was more frequently observed in HAM/TSP patients than HCs (p<0.01 by
      Mann-Whitney U-test). The length alteration of this d(CA) repeat in the MMP-9
      promoter may cause phenotypic differences among HTLV-I infected infiltrating
      cells and may thereby be in part responsible for the development of HAM/TSP.

PMID- 15465611
TI  - Interferon-beta induces transient systemic IP-10/CXCL10 chemokine release in
      patients with multiple sclerosis.
AB  - Reduction of chemokine expression induced by human recombinant Interferon (IFN)
      beta is thought to be a therapeutic mechanism of its action in the treatment of
      multiple sclerosis (MS). In vitro, IFN-beta can induce chemokine expression. Here
      we show that a single injection of IFN-beta induced a transient strong increase
      of IP-10/CXCL10 and a weak elevation of MCP-1/CCL2 plasma levels in MS patients
      on continuing treatment with IFN-beta. IP-10/CXCL10 bursts, which were not
      observed in glatiramer acetate (GA)-treated patients, correlated with occurrence
      of flu-like symptoms. Systemic IP-10/CXCL10 release induced by IFN-beta may
      influence its therapeutic effect--either negatively or positively.

PMID- 15465612
TI  - Prevalence of anti-heat shock protein antibodies in cerebrospinal fluids of
      patients with Guillain-Barre syndrome.
AB  - We examined antibodies against 10 heat shock proteins (HSPs) in cerebrospinal
      fluids (CSF) and sera from patients with Guillain-Barre syndrome (GBS).
      Significantly higher IgG antibody titers against HSP27, HSP60, HSP70 and HSP90
      family, including mycobacterial HSP65 and Escherichia coli GroEL, were found in
      CSF from GBS patients as compared with motor neuron disease. Serum IgG antibodies
      against each HSP showed no difference between GBS patients and normal controls.
      GBS seems to be induced by reactive autoimmune responses frequently triggered by
      infections. The CSF antibodies against HSPs may modify the immune responses
      and/or cell-protective functions of HSPs in the pathophysiology of GBS.

PMID- 15465613
TI  - Application of stochastic processes to participant recruitment in clinical
      trials.
AB  - The allocation of sufficient time for participant recruitment is one of the
      fundamental aspects in planning a clinical trial. This paper illustrates how a
      Poisson process can be used to determine an optimal period of time for
      participant recruitment by simulating Poisson arrival into a clinical trial. The
      simulation study provides the means to generate of an empirical probability
      density function for the recruitment time based on time-dependent changes in the
      accrual rate. From this empirical distribution, a clinical trial recruitment
      period can be planned to provide a high level of confidence (e.g., 90%
      probability) of enrolling the sample size within the planned amount of time given
      the simulation assumptions.

PMID- 15465614
TI  - Validating electronic source data in clinical trials.
AB  - The clinical trials industry relies heavily on paper-based source documents as
      the foundation for the collection of its clinical research data from human
      subjects and medical records. This focus on paper documents has been prevalent
      throughout the history of clinical trials conduct, even as computing solutions
      advanced throughout the past 20 years. With the advent of additional electronic
      capabilities recently with the growth of Internet-based products to enhance
      business operations in many fields, the clinical trials industry remains uniquely
      behind most other industries in electronic technology adoptions. Valid reasons
      exist for the slow growth of technology adoptions in clinical trial activities,
      but there are now discussions about how to use technology more effectively in
      clinical trial conduct. One area of enhanced clinical trial conduct is believed
      to be available by moving from paper-based source documents to electronic source
      documents, that is, eliminating paper from clinical data capture, and collecting
      the information initially in a computer system. An important concern in moving to
      electronic source data is the validation of such data. This paper summarizes the
      history of clinical data capture through paper and electronic advancements to
      date and identifies three reasons for the slow movement to more electronic source
      data. The paper then illustrates two methods for the validation of electronic
      source data.

PMID- 15465615
TI  - Challenges and innovations in enhancing adherence.
AB  - Adherence is a complex phenomenon involving interactions among the individual,
      the environment and the community. In an adherence workshop, a small group of
      investigators discussed their experiences with challenges and innovations
      regarding adherence gleaned from clinical research. This article summarizes the
      information and outcomes of that meeting. Guided by theoretical frameworks for
      understanding and promoting adherence, challenges in the areas of measurement,
      community-based research, and interventions were explored and innovations for
      meeting these challenges suggested. The article concludes with recommendations
      for enhancing the adherence agenda: (1) adherence research must have a well
      defined conceptual and theoretical basis; (2) individual perceptions and social
      context of behavior must be incorporated; (3) research must be undertaken as a
      collaborative process involving participants and the community. Looking ahead, it
      is clear that if we hope to develop a new and integrated model of adherence, we
      must continue to advance theory through theory testing, with particular attention
      given to mediators and diverse samples. Moreover, an interdisciplinary agenda is
      necessary to set the stage for bringing together researchers from various
      disciplines and backgrounds with both participants and community representatives.

PMID- 15465616
TI  - SEARCH for Diabetes in Youth: a multicenter study of the prevalence, incidence
      and classification of diabetes mellitus in youth.
AB  - SEARCH for Diabetes in Youth is an observational, multicenter study focusing on
      physician-diagnosed diabetes in individuals <20 years old. The study will
      estimate the population prevalence and incidence of diabetes by type, age,
      gender, and ethnicity and develop practical approaches to diabetes classification
      in 5 million children ( approximately 6% of the <20 U.S. population) with wide
      ethnic and socioeconomic representation from four geographically defined
      populations and two health plans. An estimated 6000 prevalent and 800 incident
      diabetes cases per year will be identified with annual follow-up. Cases will be
      ascertained through clinical and nonclinical resources or partnerships at each
      site. Data collection involves patient interviews, physical examinations,
      laboratory measurements (diabetes autoantibodies, fasting/stimulating C-peptide,
      hemoglobin A1c, blood glucose, lipids, urine albumin, creatinine), medical
      records reviews, and documentation of risk factors for complications and
      processes of care.

PMID- 15465618
TI  - The utility of partial cross-over designs in early phase randomized prevention
      trials.
AB  - In this note, we outline the benefits of a partial cross-over design for a class
      of experiments where the interest is the cumulative effect of dose versus
      placebo. The goal of our design strategy is to answer several complex question
      efficiently in a phase II setting with a minimal number of assumptions with an
      eye towards planning a phase III study.

PMID- 15465617
TI  - Evolution of the HALT-C Trial: pegylated interferon as maintenance therapy for
      chronic hepatitis C in previous interferon nonresponders.
AB  - The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial
      was designed to determine whether maintenance interferon therapy could slow
      disease progression in patients who had failed to eradicate hepatitis C virus
      (HCV) during prior interferon treatment (nonresponders). Ten clinical sites, a
      virological testing center, and a data coordinating center (DCC) were selected to
      collaborate in the design and implementation of the final protocol. Eligible
      patients had been treated previously with interferon for at least 12 weeks, with
      or without another antiviral, ribavirin, but still had persistent viremia.
      Because patients had received a variety of prior treatments, and as a perceived
      benefit of enrollment, we incorporated a Lead-in period of treatment with long
      acting pegylated interferon alfa-2a plus ribavirin into the study design, a
      combination believed to be more effective but not approved by the Food and Drug
      Administration at the Trial's inception. If patients failed to achieve clearance
      of virus from the blood after 20 weeks of this Lead-in therapy, they were entered
      into the main trial at week 24 and randomized to receive either a lower dose of
      pegylated interferon weekly alone or no further therapy for an additional 3 1/2
      years. The original protocol was amended later in three respects to improve
      enrollment and to adapt to Food and Drug Administration approval of the Lead-in
      therapy, including allowing patients to proceed directly to the randomized part
      of the study if treatment resembling the Lead-in had been completed. The protocol
      changes enhanced enrollment while upholding the original goals of the study and
      its integrity.

PMID- 15465619
TI  - Improving asthma symptom control in rural communities: the design of the Better
      Respiratory Education and Asthma Treatment in Hinton and Edson study.
AB  - METHODS: The prevalence of asthma in adults in the United States is approximately
      7%, and 9% of asthma patients will require hospitalization each year. Many
      patients do not seek care, as they do not recognize overuse of beta-agonists as a
      risk factor for poorly controlled asthma. However, pharmacists are able to
      identify these patients through refill information on reliever medication
      prescriptions and potentially initiate community-management opportunities for
      these patients. DESIGN: The study is a randomized, controlled trial. Patients are
      randomized to intervention or usual care. STUDY POPULATION: Patients are high
      risk asthma patients (defined as having an ER visit or hospitalization in the
      previous year, or using >2 canisters of short-acting beta-agonist in the previous
      6 months). They are identified through community pharmacies. OBJECTIVES: The
      primary objective is to determine the effect of an education and referral
      intervention program initiated by community pharmacists, working with high-risk
      asthma patients, family physicians and respiratory therapists, on asthma control,
      as measured by the Asthma Control Questionnaire (ACQ). Secondary objectives
      include determining the effect of this program on ER visits/hospitalizations,
      inhaled corticosteroid use, courses of oral steroids and FEV(1). INTERVENTION:
      The intervention includes patient education, assessment and optimization of drug
      therapy, and physician referral as needed. Patients are referred to a respiratory
      therapist within 1 week of randomization for measurement of FEV(1) and
      reinforcement of education. Patients assigned to usual care receive written
      asthma information, referral to a respiratory therapist and usual pharmacy and
      physician care. UNIQUE ASPECTS: The design of the Better Respiratory Education
      and Asthma Treatment in Hinton and Edson (BREATHE) study is unique, given the
      multidisciplinary involvement, rural and community based, pharmacist initiated
      and targets specifically high risk patients. We believe that this study will show
      that management of asthma patients, involving the major role-players in their
      asthma care, will improve their asthma control.

PMID- 15465620
TI  - Ensuring the comparability of comparison groups: is randomization enough?
AB  - BACKGROUND: It is widely believed that baseline imbalances in randomized trials
      must necessarily be random. In fact, there is a type of selection bias that can
      cause substantial, systematic and reproducible baseline imbalances of prognostic
      covariates even in properly randomized trials. It is possible, given complete
      data, to quantify both the susceptibility of a given trial to this type of
      selection bias and the extent to which selection bias appears to have caused
      either observable or unobservable baseline imbalances. Yet, in articles reporting
      on randomized trials, it is uncommon to find either these assessments or the
      information that would enable a reader to conduct them. Nevertheless, there have
      been a few published reports that contain descriptions of either this type of
      selection bias or indicators that it may have occurred. OBJECTIVE: To document
      that the same type of selection bias has been described in numerous randomized
      trials and therefore that it represents a problem deserving of greater attention.
      STUDY SELECTION: Computerized searches were not useful in locating trials with
      one or more elements that contribute to or are indicative of selection bias in
      randomized trials. We limit our treatment to trials that were previously
      questioned for susceptibility to selection bias or for large baseline imbalances.
      RESULTS: We found 14 randomized trials that appear to be suspicious for selection
      bias. This may represent only the tip of the iceberg, because the status of other
      trials is inconclusive. CONCLUSIONS: Authors of clinical trial reports should be
      required to disclose sufficient details to allow for an assessment of both
      allocation concealment and selection bias. The extent to which a randomized study
      was susceptible to selection bias should be considered in determining the
      relative contribution it makes to any subsequent meta-analysis, policy or
      decision.

PMID- 15465621
TI  - Negative results in cancer clinical trials--equivalence or poor accrual?
AB  - This study was performed to evaluate randomized cancer trials resulting negative
      regarding inadequate accrual, unsupported assumptions of equivalence and factors
      implied in such assumptions. A search in PubMed electronic data base was done for
      a sample of 800 most recently entered studies by March 2003 indexed with MESH
      term "neoplasms" and categorized according to design, intervention, outcome and
      conclusion. Minimal detectable differences with optimized power were calculated
      in each comparison according to number of patients accrued. Factors related with
      inadequate claim for equivalence in negative comparisons were also searched.
      Among the papers located, 194 met requirements and 188 were analyzed leading to
      392 valid comparisons addressing survival, anti cancer effect or major toxicity,
      235 of which resulted "negative". According to accrual, only 15.2% (ci95%, 9.9%
      to 20.3%) of negative comparisons would detect a 10% absolute difference between
      arms with 80% of chance. 53.6% (ci95%, 47.0% to 60.1%) of negative comparisons
      inadequately claimed equivalence. However, equivalence was supported by data in
      only 20.5% (ci95%, 12.6% to 28.4%) of negative comparisons that claimed for it.
      Negative comparisons based on new drugs had higher likelihood to be inadequately
      presented as supporting equivalence than those based in older drugs (66.7% vs.
      43.5%, chi-square p=0.024). We concluded that most cancer clinical comparisons
      resulting negative are affected by poor accrual. They often inadequately claim
      for equivalence without supporting data. Comparisons involving new drugs are
      specially affected by this problem. Authors, editors and readers must be more
      rigorous regarding adequate assumptions of equivalence.

PMID- 15465622
TI  - Abeta localization in abnormal endosomes: association with earliest Abeta
      elevations in AD and Down syndrome.
AB  - Early endosomes are a major site of amyloid precursor protein (APP) processing
      and a convergence point for molecules of pathologic relevance to Alzheimer's
      disease (AD). Neuronal endosome enlargement, reflecting altered endocytic
      function, is a disease-specific response that develops years before the earliest
      stage of AD and Down syndrome (DS). We examined how endocytic dysfunction is
      related to Abeta accumulation and distribution in early stage AD and DS. We found
      by ELISA and immunocytochemistry that the appearance of enlarged endosomes
      coincided with an initial rise in soluble Abeta40 and Abeta42 peptides, which
      preceded amyloid deposition. Double-immunofluorescence using numerous Abeta
      antibodies showed that intracellular Abeta localized principally to rab5-positive
      endosomes in neurons from AD brains and was prominent in enlarged endosomes.
      Abeta was not detectable in neurons from normal controls and was diminished after
      amyloid deposition in neuropathologically confirmed AD. These studies support
      growing evidence that endosomal pathology contributes significantly to Abeta
      overproduction and accumulation in sporadic AD and in AD associated with DS and
      may signify earlier disease-relevant disturbances of the signaling functions of
      endosomes.

PMID- 15465623
TI  - High frequency of mitochondrial complex I mutations in Parkinson's disease and
      aging.
AB  - Idiopathic Parkinson's disease (PD) involves a systemic loss of activity of
      complex I of the mitochondrial electron transport chain. This biochemical lesion
      plays a key pathogenic role. Transfer of PD mitochondrial DNA recapitulates this
      loss of activity and several other pathogenic features of PD suggesting that this
      lesion may arise, at least in part, from mitochondrial DNA. We investigated this
      possibility by an extensive clonal sequencing of the seven mitochondrial genes
      encoding complex I subunits in PD and age-matched control frontal cortex. Each
      gene was completely sequenced an average of 94.4 times for each subject.
      Aminoacid-changing mutations were found at the frequency of 59.3 per million
      bases in both PD and controls, corresponding to approximately 32% of the
      mitochondrial genomes in the average sample having at least one mutation in a
      complex I gene. Individual low frequency mutations had an abundance of 1-10%.
      Significant interindividual variation in mutation frequency was observed. Several
      aminoacid-changing mutations were identified and multiple PD brains but not in
      controls. Genetic algorithm analysis detected areas in ND genes with a higher
      mutation frequency in PD that allowed differentiation of PD from controls. Total
      mutational burden due to low-abundance heteroplasmy is high and may play a role
      in human disease.

PMID- 15465624
TI  - Aminopyridazines inhibit beta-amyloid-induced glial activation and neuronal
      damage in vivo.
AB  - The critical role of chronic inflammation in disease progression continues to be
      increasingly appreciated across multiple disease areas, especially in
      neurodegenerative disorders such as Alzheimer's disease. We report that late
      intervention with a recently discovered aminopyridazine suppressor of glial
      activation, developed to inhibit both oxidative and inflammatory cytokine
      pathways, attenuates human amyloid beta (Abeta)-induced glial activation in a
      murine model. Peripheral administration of the aminopyridazine MW01-070C,
      beginning 3 weeks after the start of intracerebroventricular infusion of human
      Abeta1-42, decreased the number of activated astrocytes and microglia and the
      levels of proinflammatory cytokines interleukin-1beta, tumor necrosis factor
      alpha and S100B in the hippocampus. Inhibition of neuroinflammation correlated
      with a decreased neuron loss, restoration towards control levels of synaptic
      dysfunction biomarkers in the hippocampus, and diminished amyloid plaque
      deposition. The results from this in vivo chemical biology approach provide a
      proof of concept that targeting of key glia inflammatory cytokine pathways can
      suppress Abeta-induced neuroinflammation in vivo, with resultant attenuation of
      neuronal damage.

PMID- 15465625
TI  - Association between the interleukin-1alpha gene and Alzheimer's disease: a meta
      analysis.
AB  - Inflammatory processes are involved in the pathogenesis of Alzheimer's disease
      (AD). Several studies have addressed the effects of interleukin-1 (IL-1) genes
      polymorphisms on the risk of developing AD. The results are not in full agreement
      on whether these polymorphisms are associated with the disease. To clarify this
      issue, we performed a meta-analysis of all the association studies between IL-1
      genes and AD. Due to the relatively small number of published articles, the meta
      analysis was restricted to the association of the IL-1alpha -889 C/T gene
      polymorphism and AD. Under a random effects model, the risk for the disease was
      significantly higher in subjects with the T/T genotype in comparison with both
      C/T (OR: 1.51; 95% C.I.: 1.15-1.99) and C/C (OR: 1.49; 95% C.I.: 1.09-2.03)
      subjects. There was modest heterogeneity for these effect estimates. Analysis of
      subgroups showed a significant association in patients with early-onset AD but
      not in late-onset AD. Our data support a significant but modest association
      between the T/T genotype of the IL-1alpha gene and AD.

PMID- 15465626
TI  - Glycerophosphocholine is elevated in cerebrospinal fluid of Alzheimer patients.
AB  - Experimental and clinical studies give evidence for breakdown of membrane
      phospholipids during neurodegeneration. In the present study, we measured the
      levels of glycerophosphocholine (GPCh), phosphocholine (PCh), and choline, that
      is, water-soluble metabolites of phosphatidylcholine (PtdCho), in human
      cerebrospinal fluid (CSF). Among 30 cognitively normal patients the average CSF
      levels of GPCh, phosphocholine and choline were 3.64, 1.28, and 1.93 microM,
      respectively; metabolite levels did not change with increasing age. When compared
      with age-matched controls, patients with Alzheimer's disease had elevated levels
      of all choline metabolites: GPCh was significantly increased by 76% (P<0.01),
      phosphocholine by 52% (P<0.05), and free choline (Ch) by 39%. Six patients with
      vascular dementia had lower choline and elevated phosphocholine levels, when
      compared to controls, but normal levels of GPCh. These data demonstrate that
      Alzheimer's disease is accompanied by an increased PtdCho hydrolysis in the
      brain. PtdCho breakdown seems to be mediated by phospholipase A2 and leads to
      significantly elevated levels of GPCh in CSF.

PMID- 15465627
TI  - Association analysis of genes involved in cholesterol metabolism located within
      the linkage region on chromosome 10 and Alzheimer's disease.
AB  - Epidemiological studies identified a higher risk of developing Alzheimer's
      disease (AD) among subjects with elevated cholesterol levels. This association
      may be caused by a modulation of the amyloid precursor protein (APP) processing
      in response to the cellular cholesterol content. High cholesterol levels may
      favor the amyloidogenic pathway by inhibition of the alpha-secretase probably
      leading to elevated beta-Amyloid (Abeta) production. The identification of a
      linkage peak on chromosome 10q using high Abeta as quantitative trait led us to
      examine polymorphisms of genes located on chromosome 10 involved in cholesterol
      metabolism, like Lipase A (LIPA), Cholesterol 25 hydroxylase (CH25H), and
      FLJ22476, a high density lipoprotein binding related protein. Using 286 patients
      with AD and 162 controls we analyzed several single nucleotide polymorphisms
      (SNPs) within LIPA, CH25H, and FLJ22476. None of the polymorphisms showed
      significant association with AD which contradicts recent findings on CH25H. From
      our results we conclude that the investigated genetic variations do not
      contribute to the genetic risk of AD.

PMID- 15465628
TI  - Increased galanin receptor occupancy in Alzheimer's disease.
AB  - Increased galanin (GAL) may be associated with the cognitive deficits
      characteristic of Alzheimer's disease (AD). However, both increased and decreased
      GAL receptor density has been reported in AD brain. Previous studies indicate pre
      treatment with guanine nucleotides displaces endogenous GAL from GAL receptors
      (GALR), providing an indirect measurement of GALR occupancy. In addition, pre
      treatment with guanine nucleotides may provide a more accurate measurement of
      GALR density since it would avoid the masking of GALRs by residual binding of
      endogenous GAL. Thus, in the present study, we examined the influence of pre
      treatment with guanine nucleotides on 125I-GAL binding in multiple regions of
      normal and AD brain. Our results indicate that GTP pre-treatment enhances GAL
      binding in specific regions in normal and AD brain. In addition, our results
      suggest an increase in the number of GALRs occupied by endogenous GAL in the deep
      layers of the frontal cortex and the lateral hypothalamus of AD subjects compared
      to normal subjects. The regional differences in GALR density and receptor
      occupancy between normal and AD subjects may play a role in the cognitive
      disturbances associated with the disease.

PMID- 15465629
TI  - The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human
      beta-amyloid precursor protein transgenic mice.
AB  - Metals such as zinc, copper and iron contribute to aggregation of amyloid-beta
      (Abeta) protein and deposition of amyloid plaques in Alzheimer's disease (AD). We
      examined whether the lipophilic metal chelator DP-109 inhibited these events in
      aged female hAbetaPP-transgenic Tg2576 mice. Daily gavage administration of DP
      109 for 3 months markedly reduced the burden of amyloid plaques and the degree of
      cerebral amyloid angiopathy in brains, compared to animals receiving vehicle
      treatment. Moreover, DP-109 treatment appeared to facilitate the transition of
      Abeta from insoluble to soluble forms in the cerebrum. These results further
      support the hypothesis that endogenous metals are involved in the deposition of
      aggregated Abeta in brains of AD patients, and that metal chelators may be useful
      therapeutic agents in the treatment of AD.

PMID- 15465630
TI  - BDNF-induced LTP in dentate gyrus is impaired with age: analysis of changes in
      cell signaling events.
AB  - Brain-derived neurotrophic factor (BDNF) has emerged as a major regulator of
      synaptic plasticity in the adult brain and acute BDNF infusion has been shown to
      trigger long-term potentiation (BDNF-LTP) in adult rats. Here we compared the
      effects of acute BDNF infusion in young adult and aged anesthetized rats. In
      young rats, BDNF-LTP was accompanied by increased activation of the BDNF receptor
      TrkB, and extracellular signal-regulated kinase (ERK), as well as enhanced evoked
      release of glutamate in synaptosomes prepared from DG. In aged rats, both BDNF
      LTP and the associated signaling were significantly impaired, while analysis of
      untreated hippocampal tissue from aged rats showed that activation of TrkB and
      ERK were decreased. In addition to effects in the DG, BDNF-LTP was accompanied by
      robust phosphorylation of the calcium/cAMP-responsive element binding protein
      (CREB) in tissue prepared from entorhinal cortex of both young and aged rats.
      These results suggest a cascade of presynaptic changes contributing to the
      expression of BDNF-induced LTP and show that BDNF-induced transduction mechanisms
      are attenuated with age.

PMID- 15465631
TI  - Nicotine-induced FGF-2 mRNA in rat brain is preserved during aging.
AB  - Indirect trophic actions of nicotine on brain during aging are suggested from
      observations describing nicotine as a cognitive enhancer, increasing vigilance
      and improving learning and memory, and both in vitro and in vivo models have
      demonstrated neuroprotective effects of nAChR agonists. Previously, we have
      reported that an acute intermittent (-)nicotine treatment significantly increases
      fibroblast growth factor-2 (FGF-2) mRNA and protein in several brain regions of
      rat brain. The present study was designed to analyse if nicotine-induced FGF-2
      expression in the rat brain was preserved during aging. Using in situ
      hybridization and quantitative RNase protection assay the present paper reports
      that during aging (12- and 24-month-old rats) the response of FGF-2 gene
      expression in the rat brain to nAChR stimulation by (-)nicotine is fully
      effective and involves both neurons and glial cells. The investigation was
      extended to other members of the FGF family, such as FGF-5 and -20, but this
      expression was not influenced by the (-)nicotine treatment at any age studied.
      Similarly following (-)nicotine treatment no changes were observed in FGF
      receptors (FGFR 1-3) mRNA levels in adult and aged rats. Taken together, the
      present and previous data support the hypothesis that neuroprotective effects of
      (-)nicotine and the potential beneficial effects of (-)nicotine agonists in the
      treatment of Alzheimer's and Parkinson's diseases, may at least in part involve
      an activation of the neuronal and glial FGF-2 signalling. Work is in progress to
      analyse the mechanism(s) linking nAChR activation to the up-regulation of FGF-2.

PMID- 15465632
TI  - Age-related changes in brain proDynorphin gene expression in the rat.
AB  - Dynorphin has a well-established role in feeding and gustation. Alterations in
      taste perception and feeding behavior are common with age. We hypothesized that
      proDynorphin gene expression in brain areas involved in taste and feeding
      declines with age. Male Sprague-Dawley rats were housed individually with ad
      libitum access to food and water. Brain punches of the selected regions were
      dissected out in groups of rats aged 4-6, 12-14 and 18-21 months. ProDynorphin
      mRNA (measured using a cDNA probe) decreased significantly with age in arcuate
      nucleus and amygdala; increased significantly with age in hippocampus; and was
      not significantly affected in nucleus of the solitary tract, cortex, caudate
      putamen or hypothalamic paraventricular nucleus. These data suggest an age
      related decrease in the synthesis of dynorphin in two brain regions strongly
      associated with feeding behavior, and an increase in dynorphin synthesis in a
      brain region associated with learning and memory.

PMID- 15465633
TI  - Aged-obese rats exhibit robust responses to a melanocortin agonist and antagonist
      despite leptin resistance.
AB  - To address whether defective melanocortin activation is one element of leptin
      resistance with age, we infused centrally the melanocortin agonist, MTII and
      antagonist, SHU9119 in young and old rats. Food intake, energy expenditure,
      adiposity, BAT UCP1, and leptin expression in white fat as well as hypothalamic
      expressions of MC3R, MC4R, POMC, AgRP and NPY were assessed. The MTII-evoked
      anorexia was transient whereas the SHU9119-induced hyperphagia was sustained in
      young and old. MTII elevated oxygen consumption in both ages. The oxygen
      consumption waned gradually in young but increased continuously in aged following
      MTII infusion. The MTII-mediated induction in BAT UCP1 was similarly robust in
      both ages as was the SHU9119-mediated suppression in UCP1. POMC and MC3/4
      receptor expressions were unaltered with age. These findings demonstrate the
      effectiveness of MTII to bypass leptin resistance in aged-obese rats. The equally
      strong orexigenic response to SHU9119 coupled with unaltered POMC expression and
      food intake in the young versus old suggest that melanocortin tone is unchanged
      with age despite impaired melanocortin activation by leptin.

PMID- 15465634
TI  - Age-dependent VEGF expression and intraneural neovascularization during
      regeneration of peripheral nerves.
AB  - The physiologic ability of peripheral nerves to regenerate after injury is
      impaired with aging. However, the mechanisms responsible for this phenomenon are
      still incompletely characterized. In this study, we investigated whether aging
      influences the intraneural angiogenic response that occurs after injury and
      during regeneration of peripheral nerves. We performed a crush injury of the
      sciatic nerve in old and senescence accelerated mice and found that the
      peripheral nerves of these animals are unable to locally upregulate vascular
      endothelial growth factor (VEGF), a prototypical angiogenic cytokine, after
      injury and have substantial deficits in mounting an appropriate intraneural
      angiogenic response during nerve regeneration. Our findings provide new evidence
      of possible interdependent relationships between aging, VEGF, angiogenesis, and
      nerve regeneration and suggest that vascular abnormalities might play a role in
      aging-associated neurological dysfunction, with potentially important fundamental
      and clinical implications.

PMID- 15465635
TI  - ACE genotype and cognitive decline in an African-Caribbean population.
AB  - The insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme
      (ACE) gene is believed to influence risk of cerebrovascular disease. However,
      associations with cognitive outcomes remain controversial. As far as we are
      aware, all studies to date have been carried out in white American or European
      populations. African-Caribbean populations have high prevalence rates of
      hypertension, diabetes and cerebrovascular disease but risk factors for cognitive
      outcomes remain under-researched. In a UK community sample of 148 African
      Caribbean people aged 55-75 years, we investigated the association between ACE
      genotype and cognitive decline over 3 years using a battery of repeated tests. No
      direct association was found between ACE genotype and decline. However, the
      association between increased age and cognitive decline was significantly
      stronger in people with the ACE DD genotype (odds ratio 3.6 per 5-year increase,
      95% CI: 1.9-6.7) compared to those with ID/II genotype (odds ratio 0.7, 95% CI
      0.4-1.2). This interaction was particularly strong for decline in verbal memory
      and was not apparently mediated by vascular risk factors measured at baseline.

PMID- 15465636
TI  - Age-related changes in head and eye coordination.
AB  - The effect of ageing upon head movements during gaze shifts is unknown. We have
      investigated age-related changes in head and eye coordination in a group of
      healthy volunteers. Horizontal head and eye movements were recorded in 53
      subjects, aged between 20 and 83 years, during the performance of saccades,
      antisaccades, smooth pursuit and a reading task. The subjects were divided into
      three groups, young subjects (20-40 years), middle-aged subjects (41-60 years)
      and older subjects (over 60 years). Logarithmic transformations of the head gain
      were significantly greater in the older subjects compared to the young subjects
      during the saccadic task (P=0.001), antisaccadic task (P=0.004), smooth pursuit
      at 20 degrees/s (P=0.001) and 40 degrees/s (P=0.005), but not reading. For
      saccadic and antisaccadic tasks, the increase in transformed head gain was non
      linear with significant differences between older and middle-aged subjects but
      not middle-aged and young subjects. Head movement tendencies were highly
      consistent for related tasks. Head movement gain during gaze shifts significantly
      increases with age, which may contribute to dizziness and balance problems
      experienced by the elderly.

PMID- 15465637
TI  - A comparative study of plant and animal mitochondria exposed to paraquat reveals
      that hydrogen peroxide is not related to the observed toxicity.
AB  - Rat liver mitochondria are much more susceptible to protein oxidation induced by
      paraquat than plant mitochondria. The unsaturated index and the peroxidizability
      index are higher in rat than in potato tuber. The levels of superoxide dismutase
      and glutathione reductase are concurrent with the different sensitivities to
      paraquat, with higher activities in plant mitochondria. However, glutathione
      peroxidase and catalase activities are higher in rat mitochondria. Paraquat (10
      mM) inhibited all the enzymatic activities; excluding catalase all the other
      activities were inhibited to a similar degree. The differential sensitivities of
      plant and animal mitochondria to paraquat correlate with fatty acid composition
      of mitochondrial lipids and a similar correlation was also established for some
      antioxidant enzymes. At the mitochondrial level, H(2)O(2) is not a major factor
      of paraquat toxicity since rat liver mitochondria which exhibit higher activities
      of glutathione peroxidase and catalase are however more susceptible to paraquat.

PMID- 15465638
TI  - Oxidative activation of the human carcinogen chromate by arsenite: a model for
      synergistic metal activation leading to oxidative DNA damage.
AB  - Human exposure to toxic metals and metalloids in the environment seldom occurs
      from a single pure compound. Most environmental exposure profiles are
      heterogeneous with co-exposure occurring coincident with multiple toxic metal
      species. This co-exposure to metals and metalloids in complex mixtures can result
      in a synergistic, additive or even depletive toxic response. The complexity of
      interactions presented by metal mixtures presents a need for convenient and
      sensitive methods to determine potential toxic responses from such co-exposure.
      We have studied the reaction between the two commonly associated toxic metals of
      chromate, Cr(VI), and arsenite, As(III), with regards to the ability of As(III)
      to reductively activate Cr(VI) to generate oxidative stress and DNA damage. Using
      a DCF-based fluorescent dye assay we have demonstrated that the redox reaction
      between As(III) and Cr(VI) yields high valent intermediates of chromium, Cr(V),
      that are highly oxidizing. This induction of oxidizing potential was dose
      dependent and did not occur with As(III) or Cr(VI) alone or, with the other major
      oxidation state of arsenic, arsenate, As(V). The mechanism of oxidation of DCFH
      to the fluorescent species, DCF, in this reaction was through a direct, metal
      based oxidation since addition of radical scavengers did not significantly
      decrease oxidation of the dye in this system. The addition of a ligand that
      stabilizes the high valent Cr(V) oxidation state, 2-ethyl-2-hydroxybutyric acid
      (EHBA), to the chromate and arsenite mixture resulted in an enhancement of DCF
      fluorescence. The DCF fluorescence observed with the Cr(VI) and As(III) mixture
      was also found to correlate with oxidative DNA damage as measured by a plasmid
      nicking assay. These data show how metal-metal interactions in environmental
      mixtures could result in the synergistic induction of oxidative stress and DNA
      damage. Further, these data demonstrate the utility of the DCF fluorescence assay
      as a sensitive method for screening synergistic redox interactions in metal
      mixtures.

PMID- 15465639
TI  - Effects of culture with TNF-alpha, TGF-beta and insulin on sulphotransferase
      (SULT 1A1 and 1A3) activity in human colon and neuronal cell lines.
AB  - The aim of the study was to determine whether the expression of sulphotransferase
      enzymes could be affected by the presence of cytokines or peptide hormones. The
      effects of cytokines (TNF-alpha and TGF-beta) and insulin on sulphotransferase
      (SULT 1A1 and 1A3) activity were studied in a human neuronal cell line (SK-N-SH)
      and a human gastrointestinal tract cell line (HT-29). Cells were cultured with
      varying concentrations of TNF-alpha, TGF-beta or insulin for 24 h; the SULT 1A1
      isoform in the 2 cell lines showed different optimal substrate concentrations.
      There were no direct effects of cytokines on enzyme activity. Culture with TNF
      alpha increased activity of both SULT 1A1 and 1A3 in the HT-29 cells; TGF-beta
      also increased activities of both isoforms but to a lesser extent; insulin
      increased activity of SULT 1A1 only. The cytokines and insulin had relatively
      little effect on sulphotransferase activity in the neuronal cell line. These
      results suggest that, unlike neuronal cells, gastrointestinal cells may respond
      to physiological states by altering sulphotransferase activity. As certain
      substrates such as diet-derived heterocyclic amines are bioactivated by
      sulphation to produce carcinogenic metabolites this may be a factor in the
      increased incidence of colorectal cancer in patients with inflammatory bowel
      disease or diabetes.

PMID- 15465640
TI  - Glycoprotein isolated from Solanum nigrum L. inhibits the DNA-binding activities
      of NF-kappaB and AP-1, and increases the production of nitric oxide in TPA
      stimulated MCF-7 cells.
AB  - Solanum nigrum L. (SNL) has been used in traditional folk medicine to treat
      numerous cancers. We isolated a glycoprotein (150 kDa) from SNL and tested its
      effect on the modulation of transcriptional factors (NF-kappa B and AP-1) and iNO
      production in TPA induced-MCF-7 cells, which are part of the human breast cancer
      cell line, without estrogen receptors. However, the mechanism of SNL glycoprotein
      in pharmacological and biochemical actions in cancer cells has not been studied.
      To test the effect of SNL glycoprotein on the DNA-binding activities of nuclear
      factor-kappa B (NF-kappaB) and activator protein-1 (AP-1), and nitric oxide (NO)
      production, these experiments were carried out using electrophoretic mobility
      shift assays (EMSA), western blot analysis, and the Griess method. Results in
      this experiment showed that SNL glycoprotein inhibits 12-O-Tetra decanoylphorbol
      13-acetate (TPA; 100 nM)-induced DNA-binding activities of NF-kappaB and AP-1,
      and enhances NO production in MCF-7 cells. That is, our results indicated that
      SNL glycoprotein has the capacity to modulate the TPA-induced DNA-binding
      activities of transcription factors and NO production, which play a critical role
      with respect to cytotoxicity in MCF-7 cells. Therefore, SNL glycoprotein might be
      one of the agents that blocks TPA-mediated signal responses in tumor cells.

PMID- 15465641
TI  - Hot-compressed-water decomposed products from bamboo manifest a selective
      cytotoxicity against acute lymphoblastic leukemia cells.
AB  - We examined the effect of hot-compressed-water (HCW) extracted and fractionated
      bamboo products (named as fractions A and B) on the viability of human cultured
      cell lines, derived from leukemia patients and human peripheral blood
      lymphocytes, obtained from normal adults. Fraction A was composed of xylose,
      xylooligosaccharides and water-soluble lignin, determined by high-performance
      anion exchange chromatography and spectrophotometry. Fraction B was composed of
      glucose and celooligosaccharides. It was found that Fraction B expressed a
      negligible cytotoxic effect against leukemia cells, while Fraction A reduced
      markedly (in a dose-dependent manner) the viability of leukemia cell lines,
      derived from acute lymphoblastic leukemia (ALL)--Jurkat and MOLT-4. Fraction A
      did not influence the viability of leukemia cells, derived from myelogenous
      leukemia (ML-2) or lymphoma (SupT-1), as well as the viability of normal
      lymphocytes. Furthermore, microscopic examination of ALL-derived cells treated
      with Fraction A showed typical apoptotic morphological changes such as a
      condensation of nucleus and membrane blebing, as well as phosphatidylserine
      (PSer) exposure on the cell surface. The effect of decomposed products of
      commercially available xylan against ALL-derived Jurkat cells was significantly
      lower than that of Fraction A. These results suggest that the cytotoxic effect of
      Fraction A may be attributed to apoptosis, induced by xylooligosaccharides and it
      is specific for ALL-derived cells. We speculate that the water-soluble lignin is
      an important factor, potentiating the cytotoxic effect of xylan in HCW-extracts
      from bamboo.

PMID- 15465642
TI  - Response of DNA, proteins and membrane bilayer in the digestive gland cells of
      freshwater mussel Unio tumidus to tannins exposure.
AB  - Exposure of digestive gland cells (Unio tumidus) in in vitro study to tannins
      (tannic, ellagic and gallic acid) caused changes in three types of cellular
      macromolecules, i.e. lipids, proteins and DNA. Two fluorescence probes: TMA-DPH
      and 12-AS were used to assess the membrane fluidity after incubating cells with
      different concentrations of tannins (1-60 microM). It was noticed that tannins
      increased the fluidity in the internal region of the lipid bilayer, but no
      changes at the surface of the plasma membrane were observed. The number of
      protein-bound carbonyl groups was quantitated spectrophotometrically using 2,4
      dinitrophenylhydrazine (DNPH) assay. Oxidative modification of proteins increased
      in the cells exposed to tannins in a concentration-dependent manner. Results also
      showed an increase in carbonyl groups formation after exposing the cells to
      complex: tannin-Cu(2+) ions. We also investigated the effect of tannins on the
      level of nuclear DNA damage using the comet assay. We showed that these compounds
      at 15, 30 and 60 microM induced DNA damage. At these concentrations cell
      viability measured by trypan blue exclusion assay was not reduced by more than
      30%. We also added Cu(2+) ions at 50 microM to assess the influence of the
      complex tannin-Cu(2+) on DNA lesions. The same method was used to study the
      possibility to repair this damage in DNA. Experimental data showed that tested
      polyphenolic acids do not contribute to the induction of strand breaks in nucleic
      acid at the smallest dose--1 microM and in this range they have a protective
      effect against the activity of 50 microM Cu(2+) ions.

PMID- 15465643
TI  - Prooxidant activity of curcumin: copper-dependent formation of 8-hydroxy-2'
      deoxyguanosine in DNA and induction of apoptotic cell death.
AB  - Curcumin, a well-known antioxidant in a principal ingredient of turmeric, acted
      as a prooxidant causing a copper-dependent DNA damage and the induction of
      apoptosis. Treatment of DNA from plasmid pBR322 and calf thymus with curcumin
      plus copper ion caused strand scission and the formation of 8-hydroxy-2(')
      deoxyguanosine in DNA. Addition of catalase protected DNA from the curcumin
      dependent injuries, indicating that hydroxyl radical may participate in the DNA
      damage. Flow cytometry analysis showed that curcumin caused an apoptotic cell
      death of HL60 cells in a dose- and time-dependent manner. Curcumin-mediated
      apoptosis was closely related to the increase in intracellular reactive oxygen
      species. On the contrary, capsaicinoids, which have a ortho-methoxy phenolic
      structure without beta-diketone in the side chain, did not produce 8-hydroxy-2(')
      deoxyguanosine. Capsaicin further did not induce apoptosis of HL60 cells, but
      rather protected cells from prooxidant-induced apoptosis. Curcumin can generate
      reactive oxygen species as a prooxidant in the presence of transition metals in
      cells, resulting in DNA injuries and apoptotic cell death. The prooxidant action
      of curcumin may be related to the conjugated beta-diketone structure of this
      compound.

PMID- 15465644
TI  - Electrochemical generation of active oxygen into aqueous solutions for organism
      detoxification.
AB  - A method has been developed to synthesize long-living active oxygen in Na(2)SO(4)
      solution. The inactivity of oxygen containing synthesized solutions toward formed
      elements of blood has been observed. The interactions of some metabolites and
      xenobiotics in blood and plasma with the active oxygen solution were
      investigated. The kinetic parameters of the oxidizing detoxification of blood
      containing endotoxins and xenobiotics were obtained. Solutions containing sodium
      sulfate and active oxygen accelerate metabolic processes. The synthesized
      solution continued to detoxify through oxidizing reactions during a 72 h period.

PMID- 15465645
TI  - Proliferative responses observed following vancomycin treatment in renal proximal
      tubule epithelial cells.
AB  - Vancomycin (VAN) is a glycopeptide antibiotic used to treat gram-positive
      infections. Nephrotoxicity is a common side effect observed with vancomycin
      therapy. However, the mechanism of vancomycin-induced nephrotoxicity has not been
      fully characterized. In this study we examined the effect of vancomycin on
      cellular proliferation in renal proximal tubule cells. A dose- and time-dependent
      increase in cell number and total cellular protein was observed following
      vancomycin exposure. Vancomycin exposure also caused an increase in BrdU
      incorporation followed by the accumulation of renal proximal tubule cells in
      G(2)/M phase of the cell cycle. These effects were inhibited by pretreatment with
      the mitogen-activated protein kinase inhibitor, PD098059, suggesting an
      association between the cell proliferative effect of VAN and the induction of the
      mitogen-activated protein kinase signaling pathway. Mitochondrial function in
      renal proximal tubule cells was assessed using oxygen consumption and ATP
      concentrations. We observed an increase in oxygen consumption and ATP
      concentrations following short-term exposure to vancomycin. Together, our data
      suggest that vancomycin treatment produces alterations in mitochondrial function
      that coincide with a cell proliferative response in renal proximal tubule
      epithelial cells.

PMID- 15465646
TI  - Sensitivity of delta-ALA-D (E.C. 4.2.1.24) of rats to metals in vitro depends on
      the stage of postnatal growth and tissue.
AB  - Heavy metals, like cadmium, lead, and mercury, are potential toxic substances.
      The exposure to these metals can cause renal disturbances and neurological
      alterations. Young rats are more sensitive to harmful agents than adult animals.
      Delta-ALA-D enzyme acts as a biomarker of these exposures, since it has high
      affinity for divalent metals. The purpose of this search was to investigate the
      sensitivity of delta-ALA-D from suckling rats to cadmium, lead or mercury in
      vitro. IC(50) for delta-ALA-D activity of brain, kidneys, and liver from rats
      with ages between 1 and 6, 8 and 13 or 17 and 21 days was determined using metals
      concentrations that range from 0 to 200 microM for CdCl(2), 0 to 600 microM for
      HgCl(2) and from 0 to 50 microM for lead acetate. The results demonstrated that
      the cerebral delta-ALA-D activity is more sensitive to lead acetate than to
      cadmium and mercury. Delta-ALA-D from hepatic tissue is the most resistant to
      presence of mercury chloride in assay medium. Lead and cadmium are more toxic to
      renal enzyme than mercury. To sum up, the sensitivity of delta-ALA-D enzyme of
      young rats to heavy metals studied depends on the phase of development and
      tissue.

PMID- 15465647
TI  - TCDD and PCBs inhibit breast cancer cell proliferation in vitro.
AB  - The effects on cell proliferation of arylhydrocarbon receptor (AhR) agonists in
      estrogen-responsive T47D and ZR-75-1 cells were investigated. 2,3,7,8
      Tetrachlorodibenzo-p-dioxin (TCDD) and the non-ortho-substituted polychlorinated
      biphenyl (PCB) congeners, PCB 77, PCB 81, PCB 126, and PCB 169 each inhibited
      17beta-estradiol (E(2))-stimulated cell proliferation in a dose-responsive
      manner. In the absence of added E(2), TCDD, PCB 77, PCB 81, and PCB 169 had no
      significant effect on cell proliferation, while PCB 126 at high concentrations
      caused slight elevations. The order of effective inhibition of E(2)-stimulated
      cell proliferation by the PCB congeners was: PCB 81>PCB 126 approximately = PCB
      169>PCB 77. In the comparative literature, mammalian TEFs for these congeners
      toxic potency are in the order: PCB 126>PCB 169>PCB 81 approximately = PCB 77
      [Organohalogen Compd. 34 (1997) 237]. Our results thus show an unexpected
      different pattern for the inhibitory effects of PCBs congeners on E(2)-mediated
      cell proliferation.

PMID- 15465648
TI  - Studies on the joint cytotoxicity of Wheat Germ Agglutinin and monensin.
AB  - Wheat Germ Agglutinin (WGA) cytotoxicity has been studied using two human
      leukemia cell lines, Molt3 and K562, and human peripheral blood mononuclear cells
      (PBMC). In spite of similar binding at the cell surface, WGA was found to promote
      cell death to a different extent in Molt3, K562 and PBMC and to induce different
      death events leading to apoptosis in Molt3 and either apoptosis and necrosis in
      K562 cells and PBMC. In Molt3 but not in K562 cells, WGA cytotoxicity could be
      potentiated 66-200 fold by 50 nM monensin, a carboxylic ionophore that perturbs
      the intracellular trafficking of endocytosed molecules. Synergism between the
      cytotoxic activities of WGA and monensin was demonstrated in Molt3 cells by
      comparing non toxic, or slightly toxic, doses of WGA and monensin alone or in
      combination. These results show that the cytotoxic effect of WGA is dependent on
      internalisation events which may differ among the cell lines used. WGA and
      monensin can enter the human diet being a component of wheat germ and an
      antibiotic used for zootechnic reasons in the bioindustry, respectively. These
      data reveal the synergistic effect between two dietary molecules, otherwise per
      se toxic at much higher concentrations, with possible implications for human and
      animal health.

PMID- 15465649
TI  - Drynariae Rhizoma promotes osteoblast differentiation and mineralization in MC3T3
      E1 cells through regulation of bone morphogenetic protein-2, alkaline
      phosphatase, type I collagen and collagenase-1.
AB  - In a previous study (Jeong et al., 2003, Inhibition of Drynariae Rhizoma extracts
      on bone resorption mediated by processing of cathepsin K in cultured mouse
      osteoclasts. International Immunopharmacology 3, 1685-1697), treatment of
      osteoclasts-containing long bone cells with Drynariae Rhizoma (DR) extract
      prevented the intracellular maturation of cathepsin K and thus, it was considered
      that DR is a pro-drug of a potent bone resorption inhibitor. To further clarify
      the role of DR in ossification, we investigated the effects of DR on the
      proliferation and differentiation of osteoblastic cell lines in vitro. In this
      study, the bone effect of DR is studied. We assessed the effects of DR on
      osteoblastic differentiation in nontransformed osteoblastic cells (MC3T3-E1) and
      rat bone marrow cells. DR enhanced alkaline phosphatase (ALP) activity and
      mineralization in a dose- and time-dependent fashion. This stimulatory effect of
      the DR was observed at relatively low doses (significant at 50-150 microg/ml and
      maximal at 150 microg/ml). Northern blot analysis showed that the DR (100
      microg/ml) increased in bone morphogenetic protein-2 as well as ALP mRNA
      concentrations in MC3T3-E1 cells. DR (60 microg/ml) slightly increased in type I
      collagen mRNA abundance throughout the culture period, whereas it markedly
      inhibited the gene expression of collagenase-1 between days 15 and 20 of culture.
      These results indicate that DR has anabolic effects on bone through the promotion
      of osteoblastic differentiation, suggesting that it could be used for the
      treatment of common metabolic bone diseases such as osteoporosis.

PMID- 15465650
TI  - Protein binding capacity in vitro changes metabolism of substrates and influences
      the predictability of metabolic pathways in vivo.
AB  - Large numbers of lipophilic molecules are attached to fractions of serum protein,
      e.g. albumin, in vivo. Cell culture medium of most in vitro hepatocyte models for
      the prediction of metabolism does not contain albumin. Consequently, in vitro
      availability and metabolism of substrates could differ significantly from the in
      vivo situation. The influence of albumin on the in vitro metabolism was tested on
      a new lipophilic compound. METHODS: Primary human and rat hepatocytes were
      cultured in a collagen sandwich configuration and incubated with (14)C-labeled
      compound X127 that is known to exhibit a high propensity to bind to plastic
      surfaces. Groups contained either 1% (w/v) BSA or none. Substrates as well as
      metabolism products were determined with radio-HPLC and radioactivity levels in
      the medium were recorded. RESULTS: Quantitative differences were seen in the
      distribution of the compound in BSA and non BSA containing groups, thus
      indicating a substantial binding of the compound to polystyrol surfaces of cell
      culture dishes. Metabolic radio-HPLC profiles showed different patterns after 24
      h of incubation between the two species as well as between the BSA- and non-BSA
      groups within the species. CONCLUSIONS: With addition of albumin the adherance of
      lipophilic substrates and metabolites to cell culture dish surfaces can be
      neutralized and in vitro systems can more closely mimic the in vivo situation.

PMID- 15465651
TI  - Surfactant and UV-B-induced damage of the cultured bovine lens.
AB  - PURPOSE: To evaluate in vitro methods for testing the toxicity of the
      surfactants, sodium dodecyl sulfate (SDS) and benzalkonium chloride (BAK), and
      Ultraviolet (UV)-B radiation to the bovine lens. METHODS: Lenses were dissected
      from bovine eyes--obtained from a local abattoir--and incubated in M199 culture
      medium at 37 degrees C, with 4% CO(2) and 96% air atmosphere. For the SDS and BAK
      experiments, the lenses (n = 153) were exposed directly to 0.001%, 0.01%, 0.1%,
      and 1.0% solutions for 15 min. These lenses were then rinsed five times each with
      saline and medium. Another group of lenses (n = 36) was irradiated with broadband
      UV-B at energy levels of 1.0 and 2.0 J/cm(2) (0.445 and 0.89 J/cm(2) in the
      biologically effective energy levels). For all of the above experiments, lens
      optical quality and cellular viability of lens epithelial cells were evaluated.
      RESULTS: The analysis of optical quality, using a scanning laser in vitro assay
      system, of exposed lenses treated with SDS and BAK at concentrations of 0.01%,
      0.1%, and 1.0%, and with UV-B at energy levels of 0.445 and 0.89 J/cm(2) showed a
      dose- and time-dependent increase in back vertex distance (BVD) variability,
      indicating loss of sharp focus in comparison with control lenses. Both 0.001% SDS
      and 0.001% BAK-treated lenses did not show any optical damage until 8-days after
      exposure. Lenses treated with 0.01% SDS showed recovery from optical damage 6
      days later after exposure. Optical damage was not shown immediately for UV-B
      exposed lenses. The Alamar Blue assay data for SDS, BAK and UV-B-exposed lenses,
      except the 0.001% SDS treated lens group, showed also dose- and time-dependent
      decreases in cellular viability in comparison with the control lenses, and there
      was no cellular recovery during the entire culture period. Lenses treated with
      0.001% SDS did not show biological damage until 8-days after exposure. It appears
      that cellular changes appeared earlier than optical changes. CONCLUSIONS: The
      findings suggest that cultured bovine lenses can be evaluated by assays that
      probe optical properties and cellular function after exposure to surfactants and
      UV-B irradiation, and that the optical and biological assay methods are valuable
      for in vitro mild ocular toxicity research.

PMID- 15465652
TI  - Corneal permeability in a redesigned corneal holder for the bovine cornea opacity
      and permeability assay.
AB  - The bovine cornea opacity and permeability assay (BCOP) is a proposed alternative
      to the Draize rabbit test for potential eye irritants. In the standard BCOP,
      bovine corneas are mounted in a holder on a flat surface between two identical
      chambers. The flat configuration of the standard holder does not conform to the
      normal curved shape of the bovine cornea and it comes into direct contact with
      the cornea tissue. Mounting corneas in this holder causes extensive damage to
      both epithelial and endothelial corneal cell layers. Our laboratory has designed
      a new holder that allows the cornea to maintain its natural curvature and does
      not damage the cornea. Previous tests, using both the new and standard holders,
      and comparing corneal opacity, hydration and endothelial morphology, have shown
      that the new holder is a significant improvement over the standard holder. The
      present study extends the comparisons of the new and standard holders to
      measurement of corneal fluorescein permeability. The permeability (ng/cm(2)/min)
      of intact corneas, corneas with no epithelium, and corneas treated with 1% NaOH,
      isopropanol, acetone, 30% trichloroacetic acid or 30% sodium dodecysulfate for
      either 1 or 10 min was determined by measuring fluorescence of samples taken from
      the endothelial chamber after 90 min epithelial exposure to 0.04% sodium
      fluorescein. In all trials, the redesigned holders yielded not only lower
      permeability measurements but also decreased measurement variability. The data
      provide further evidence that the new holder is an improvement over the standard
      holder and should be incorporated into a new protocol for the BCOP.

PMID- 15465653
TI  - Interaction of non-ionic surfactants with hepatic CYP in Prochilodus scrofa.
AB  - Cytochromes P450 (CYP) constitute a superfamily of hemeproteins that play a vital
      role in the metabolism of a wide variety of endogenous and xenobiotic compounds.
      Xenobiotic metabolism and the role of CYP are of particular interest in studies
      regarding the prevention of the damage caused by chemical pollutants. We
      investigated, in this study, the interaction of Triton X-100 and Tween 80 with
      CYP and antioxidant defenses in Curimbata, a Brazilian fish. Aiming to clarify
      the effects of non-ionic surfactants in the monooxigenase system of fish through
      in vitro study, the effects of Triton X-100 and Tween 80 were analyzed using
      monooxygenases and antioxidant system as experimental model. Total CYP and EROD
      were strongly inhibited by Triton X-100 and Tween 80 in a concentration-dependent
      way; the content of CYP was reduced until zero while EROD activity was completely
      inhibited in the presence of Triton X-100 and more than 40% inhibited in the
      presence of Tween 80. Each surfactant causes a different effect on each
      antioxidant enzyme. No effect was detected in SOD activity in the presence of
      even Triton X-100 or Tween 80. Triton X-100 increase catalase activity, while
      Tween 80 decreases this enzyme activity. The molecular structure of the
      surfactants causes the alteration of this system, since they are able to interact
      with the microsomal protein, especially with monooxigenase's components, altering
      their conformation and, consequently destroying their function. Our results
      suggest that surfactants can interact with components of the microsomal system
      leading to inhibition of CYP. Therefore, CYP activity, which has been used as a
      biomarker of xenobiotic exposure, should be used as a marker in association with
      other enzymes.

PMID- 15465654
TI  - Viability assessment in sandwich-cultured rat hepatocytes after xenobiotic
      exposure.
AB  - Troglitazone, bosentan and glibenclamide inhibit the bile salt export pump (Bsep)
      which transports taurocholate into bile. Sandwich-cultured rat hepatocytes
      maintain functional sodium taurocholate co-transporting polypeptide and Bsep
      transport proteins, and may be useful to study inhibition of transport by
      xenobiotics at concentrations below the lowest observable adverse effect level
      (LOAEL). The purpose of this study was to compare viability assessments
      determined with the neutral red, lactate dehydrogenase (LDH), alamar blue, 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and propidium iodide
      assays in sandwich-cultured rat hepatocytes following exposure to xenobiotics
      known to inhibit Bsep, and to define the LOAEL for these xenobiotics in this
      system. The neutral red assay was not amenable to use in this model due to
      crystal formation on the collagen. Troglitazone decreased viability in every
      assay examined, with a LOAEL approximately 100 microM. Bosentan also decreased
      viability as measured by the LDH, MTT and propidium iodide assays, with a LOAEL
      approximately 200 microM; however, a significant decrease in viability was not
      observed with the alamar blue assay. Glibenclamide did not decrease viability
      with any assay at the xenobiotic concentrations examined in this study. Based on
      the results of this study, the LDH or propidium iodide assays would be the
      methods of choice to assess viability in sandwich-cultured rat hepatocytes after
      xenobiotic exposure.

PMID- 15465655
TI  - The use of precision-cut liver slices from male Wistar rats as a tool to study
      age related changes in CYP3A induction and in formation of paracetamol
      conjugates.
AB  - Precision-cut liver slices (PCLS) offer a lot of advantages because all
      heterogeneity and cell-cell interactions within the original tissue matrix are
      maintained. This in vitro model was used to study the effect of ageing on certain
      aspects of drug metabolism and liver function in young (3 months), adult (9
      months) and old (24 months) Wistar male rats. Protein synthesis, an important
      liver function, was not modified in young, adult and old rats, suggesting that
      ageing does not impair liver functionality but it affects some specific targets.
      Among them, a decrease in total P450 in liver microsomes and the loss of CYP3A23
      inducibility in PCLS were clearly observed in old rats as compared to adult rats.
      Finally, the amount of total paracetamol conjugates was not modified between 9
      and 24 months but in old rats, sulfoconjugation of paracetamol, its major route
      of elimination, was decreased.

PMID- 15465656
TI  - Expression and activities of several drug-metabolizing enzymes in LLC-PK1 cells.
AB  - LLC-PK1 cells are frequently used in toxicology research, but little information
      is available concerning the capacity of these cells to metabolize xenobiotics. We
      examined the expression and activities of cytochromes P450 (P450) 1A1/1A2 (CYP
      1A1/1A2), 2E1 (CYP 2E1), flavin monooxygenase (FMO), 5-lipoxygenase (5-LO) and
      prostaglandin H synthase (PHS)-associated cyclooxygenase-1 (COX-1). We prepared
      S9 fractions from LLC-PK1 cells, rat liver, and rat kidney, and measured enzyme
      activities using ethoxyresorufin O-deethylation (EROD) for CYP 1A1/1A2 and
      ethoxycoumarin O-deethylation (ECOD) for CYP 2E1, benzydamine N-oxidation (BNO)
      for FMO, leukotriene B(4) (LTB(4)) formation for 5-LO, and thromboxane B(2)
      (TXB(2)) formation for COX-1 activities. To assure that product formation was due
      to enzymatic activity, we used the following inhibitors: 1-aminobenzotriazole
      (ABT) for P450, methimazole for FMO, caffeic acid for 5-LO and acetylsalicylic
      acid (ASA) for COX-1. We also performed Western blot analysis to confirm our
      observations. All five enzyme activities were demonstrable in rat liver at much
      greater levels than in rat kidney S9 fractions. Activities in LLC-PK1 cells were
      significantly lower than activities in rat liver S9 fraction and generally less
      than activities in rat kidney S9 fraction. Enzyme inhibitors decreased product
      formation in all three tissues and Western blot analysis supported our
      observations of low enzyme activity in LLC-PK1 cells. These results indicate that
      LLC-PK1 cells have very low content of relevant drug-metabolizing enzyme
      activities.

PMID- 15465657
TI  - Mutagenic activity in waste from an aluminum products factory in
      Salmonella/microsome assay.
AB  - The mutagenic activity of waste material originating from an aluminum products
      factory was determined by the Salmonella/microsome assay, using the bacterial
      strains TA100, TA98 and YG1024. The material was obtained by sweeping the factory
      floor at the end of the work shift. Organic compounds were extracted by
      ultrasound for 30 min in dichloromethane or 70% ethanol. After evaporation of
      solvent, these extracts were dissolved in dimethylsulfoxide, and tested for the
      mutagenic activity at varying concentrations. All the extracts from the factory
      had mutagenic activity, especially in the YG1024 strain, suggesting the presence
      of aromatic amines, later confirmed by chemical analysis. The TA98 strain also
      showed mutagenic activity, though it did not exhibit the highest mutagenicity
      index observed with the YG1024 strain. In TA100, mutagenic activity was not
      observed. This study should serve as an alert to management and those who are
      occupationally exposed, and as a warning that this type of waste should not be
      discarded in the environment without any control.

PMID- 15465658
TI  - Effect of recombinant interferon-alpha on streptozotocin-induced chromosome
      aberrations and sister-chromatid exchanges in hamster cells.
AB  - We assessed the effect of recombinant IFN-alpha-2a (rIFN-alpha-2a) on the
      induction of CAs and sister-chromatid exchanges (SCEs) by the methylating
      compound streptozotocin (STZ), in Chinese Hamster Ovary (CHO) cells. The cytokine
      was added to cell cultures 30 min before STZ and left in the culture medium until
      the end of the treatment. A statistically significant increase in the frequency
      of CAs and SCEs was observed following treatment with STZ alone (p < 0.05)
      compared to control, whereas treatments with rIFN-alpha-2a alone did not produce
      any significant increase of CAs or SCEs over the control values (p < 0.05).
      Moreover, rIFN-alpha-2a had a marked inhibitory effect on the frequency of STZ
      induced CAs--both chromosome- and chromatid-type--(p < 0.05) but was unable to
      prevent SCEs induced by the antibiotic (p > 0.05). A decrease in the replication
      index (RI) was observed in the combined treatments compared with STZ alone
      treated cultures, indicating inhibition of DNA synthesis. It is suggested that
      rIFN-alpha-2a exerts its protective action against the induction of CAs by STZ by
      stimulating DNA repair.

PMID- 15465659
TI  - Cloning and characterization of the cDNA for the Brazilian Cratomorphus
      distinctus larval firefly luciferase: similarities with European Lampyris
      noctiluca and Asiatic Pyrocoelia luciferases.
AB  - Studies on firefly (Lampyridae) luciferases have focused on nearctic species of
      Photinus and Photuris and Euroasiatic species of Lampyris, Luciola, Hotaria, and
      Pyrocoelia. Despite accounting for the greatest diversity of fireflies in the
      world, no molecular studies have been carried out on the highly diverse genera
      from the neotropical region. Here we report the luciferase cDNA cloning for the
      larva of the Brazilian firefly Cratomorphus distinctus. The cDNA has 1978 bp and
      codes for a 547-residue-long polypeptide. Noteworthy, sequence comparison as well
      as functional properties show the highest degree of similarity with Lampyris
      noctiluca (93%) and Pyrocoelia spp. (91%) luciferases, suggesting a close
      phylogenetic relationship despite the geographical distance separating these
      species. The bioluminescence emission spectrum peaks at 550 nm and, as expected,
      is sensitive to pH, shifting to 605 nm at pH 6. The kinetic properties of the
      recombinant luciferase were similar to those of other firefly luciferases.

PMID- 15465660
TI  - Effects of proteinase inhibitors on fertilization in sea lamprey (Petromyzon
      marinus).
AB  - A search for alternative sterilants in parasitic fish encouraged us to explore
      the usefulness of proteinase inhibitors for this purpose. Fertilization in sea
      lamprey species (Petromyzon marinus L.) was inhibited by chymotrypsin and trypsin
      inhibitors 4'-acetamidophenyl 4-guanidinobenzoate (AGB), chymostatin, tosyl-L
      lysine chloromethyl ketone (TLCK), and N-tosyl-L-phenylalanine chloromethyl
      ketone (TPCK) when these substances were added into a fertilization medium at the
      time of fertilization. Preincubation of eggs before fertilization with 100 microM
      TPCK, but not TLCK, resulted in inhibition of fertilization. Conversely,
      preincubation of spermatozoa with TLCK, but not TPCK, produced inhibition of
      fertilization. These data suggest the involvement of the chymotrypsin-like
      activity of eggs and trypsin-like activity of spermatozoa in fertilization.
      However, enzymes present in sperm suspensions were able to hydrolyze a
      chymotrypsin substrate N-glutaryl-L-phenylalanine-p-nitroanilide (GPNA) but not
      trypsin substrate N-alpha-benzoyl-DL-arginine-p-nitroanilide (BAPNA). The nature
      of this activity can be characterized as serine protease and our results indicate
      the involvement of serine proteinases in the fertilization of sea lamprey.

PMID- 15465661
TI  - Effect of dietary protein intake on plasma leucine flux, protein synthesis, and
      degradation in sheep.
AB  - Combined experiments of an isotope dilution method of [1-(13)C]leucine with open
      circuit calorimetry and a nitrogen (N) balance test were applied to determine the
      effect of dietary crude protein (CP) intake on plasma leucine flux and protein
      synthesis and degradation in four sheep. The experiment was conducted in a 3 x 4
      Latin rectangle design of three 3-week periods. Dietary CP intake was 5.6, 7.7,
      and 10.8 g/(kg(0.75) x d). Metabolizable energy intake was 120% of requirement
      for all dietary treatments. [1-(13)C]Leucine was intravenously infused for 8 h
      and blood and breath samples were collected during the latter 2-h period of
      infusion. Isotopic enrichments of plasma [1-(13)C]leucine, alpha-[1
      (13)C]ketoisocaproic acid, and exhaled (13)CO(2) were determined. For the N
      balance test, N digestibility, N excretion in urine, and protein balance (N x
      6.25) increased with increasing dietary CP intake. Rates of plasma leucine
      turnover, protein synthesis, and degradation changed toward reduction with
      increased dietary CP intake. It is likely that in sheep, high CP intake enhances
      protein deposition with reduced protein degradation rather than increased protein
      synthesis.

PMID- 15465662
TI  - Biological activities of marine sesquiterpenoid quinones: structure-activity
      relationships in cytotoxic and hemolytic assays.
AB  - Sesquiterpenoid quinones from marine sponges and their semisynthetic derivatives
      were compared for cytotoxicity on developing eggs of sea urchin
      Strongylocentrotus nudus and Ehrlich carcinoma cells, and for hemolytic
      activities on mice red blood cells. Structure-activity studies showed that
      activities of these compounds with a hydroxyl group at C-20 ((2), (7)) were
      higher than their methoxyl ((1), (8)) and amino ((4), (5)) derivatives at this
      position. Sesquiterpenoid quinones containing a dihydropyran ring ((10)-(12)) had
      lower activity than noncyclic compounds. The structure of the terpenoid moieties
      of the compounds had no significant influence on biological activity. There was a
      direct correlation between cytotoxic and hemolytic activities. This report
      discusses the mechanism of action employed by these compounds against cell
      membranes.

PMID- 15465663
TI  - Molecular cloning, expression and characterization of glutathione S-transferase
      from Mytilus edulis.
AB  - The gene coding for glutathione S-transferase (GST) has been isolated from the
      Mytilus edulis hepatopancreas. Open reading frame analysis indicated that the M.
      edulis GST (meGST) gene encodes a protein of 206 amino acid residues with a
      calculated molecular mass of 23.68 kDa. The deduced amino acid sequence showed
      high sequence similarity with the sequence of the pi class GST. The meGST was
      expressed in Escherichia coli, and the recombinant meGST was purified by affinity
      chromatography and characterized. The recombinant meGST exhibited high activity
      towards the substrates ethacrynic acid (ECA) and 1-chloro-2,4-dinitrobenzene
      (CDNB). Kinetic analysis with respect to CDNB as substrate gave a K(m) of 0.68 mM
      and a V(max) of 0.10 mmol/min per mg protein. The recombinant meGST had a maximum
      activity at approximately pH 8.5, and its optimum temperature was 39 degrees C.
      The predicted three-dimensional structure of the meGST revealed the N-terminal
      domain possesses a thioredoxin fold and the six helices of the C-terminal domain
      make a alpha-helical bundle. These features indicate that the meGST belongs to pi
      class GST.

PMID- 15465664
TI  - 17beta-Estradiol affects osmoregulation in Fundulus heteroclitus.
AB  - The effect of 17beta-estradiol (E(2)) on osmoregulatory performance was examined
      in the euryhaline killifish, Fundulus heteroclitus. Fish were injected once with
      1, 2 and 5 microg g(-1) E(2) and, 6 h after injection, transferred from 1 ppt
      seawater (SW) to full strength SW (40 ppt) or from SW to 1 ppt SW. In another set
      of experiments, fish were injected four times on alternate days with 2 microg g(
      1) E(2) and then, 6 h after the last injection, transferred from 1 ppt SW to SW
      or from SW to 1 ppt SW. Fish were sampled 18 h after transfer (i.e., 24 h post
      injection), and plasma osmolality, Na(+) and Cl(-) concentration and gill K(+)
      pNPPase activity (a reflection of the sodium pump) were examined. Transfer from 1
      ppt SW to SW resulted in significantly increased plasma osmolality, but did not
      affect gill K(+)-pNPPase activity. A single dose of E(2) (1, 2 and 5 microg g(
      1)) prior to transfer from 1 ppt SW to SW increased plasma osmolality and
      decreased gill K(+)-pNPPase activity in a dose-dependent manner. Prolonged
      treatment with E(2) increased plasma osmolality and decreased gill K(+)-pNPPase
      activity in 1 ppt SW-adapted fish. Transfer of fish thus treated from 1 ppt SW to
      SW increased plasma osmolality and did not alter gill K(+)-pNPPase activity.
      Transfer from SW to 1 ppt SW had no significant effect on plasma osmolality or
      gill K(+)-pNPPase activity. Only the highest single dose of E(2) (5 microg g(-1))
      prior to transfer from SW to 1 ppt SW decreased gill K(+)-pNPPase activity.
      Prolonged treatment with 2 microg g(-1) E(2) decreased gill K(+)-pNPPase activity
      only following transfer from SW to 1 ppt SW. The results substantiate an
      inhibitory action of E(2) on hypoosmoregulatory capacity in this euryhaline
      teleost.

PMID- 15465665
TI  - Development and characterization of a competitive polyclonal antibody enzyme
      immunoassay for salmon insulin-like growth factor-II.
AB  - This paper describes the development and validation of a competitive, polyclonal
      antibody enzyme-immunoassay (EIA) for the measurement of salmon and trout insulin
      like growth factor-II (IGF-II). A polyclonal antiserum was raised against a
      synthetic peptide epitope, corresponding to amino acid residues 1-9 of the N
      terminus of mature Atlantic salmon (Salmo salar) IGF-II. The antiserum was
      purified by hydrophobic charge induction chromatography (HCIC). The partially
      purified immunoglobulins were used in an enzyme-immunoassay system (EIA)
      resulting in a highly specific assay for salmon IGF-II with cross-reactivity of
      less than 0.01% for recombinant salmon IGF-I and recombinant salmon growth
      hormone (GH), and 5.57% for salmon insulin (sIns). The recombinant salmon IGF-II
      (rsIGF-II) standard curve limit of detection was 1.37 ng/ml with an EC(50) of
      44.97+/-0.82 ng/ml. Intra- and interassay coefficients of variation were
      determined at 7.47% (n=15) and 7.42% (n=15), respectively. Added rsIGF-II was
      adequately recovered from acid-treated Atlantic salmon and rainbow trout
      (Oncorhynchus mykiss) plasma samples. Parallel dose-response inhibition curves
      were demonstrated for the plasma of both fish species tested. Circulating IGF-II
      levels of 22.26+/-2.66 and 18.24+/-1.43 ng/ml were determined for acid-treated
      plasma of normal adult Atlantic salmon and rainbow trout, respectively. This EIA
      should prove to be useful in the study of factors which influence circulating
      plasma levels of IGF-II in these fish species.

PMID- 15465666
TI  - Ecto-5'-nucleotidase activity in brain membranes of zebrafish (Danio rerio).
AB  - Adenosine, a well-known neuromodulator, may be formed intracellularly in the CNS
      from degradation of AMP and then exit via bi-directional nucleoside transporters,
      or extracellularly by the metabolism of released nucleotides. This study reports
      the enzymatic properties of an ecto-5'-nucleotidase activity in brain membranes
      of zebrafish (Danio rerio). This enzyme was cation-dependent, with a maximal rate
      for AMP hydrolysis in a pH range of 7.0-7.5 in the presence of Mg(2+). The enzyme
      presented a maximal activity for AMP hydrolysis at 37 degrees C. The apparent
      K(m) and V(max) values for Mg(2+)-AMP were 135.3+/-16 microM and 29+/-4.2 nmol
      Pi.min(-1).mg(-1) protein, respectively. The enzyme was able to hydrolyze both
      purine and pyrimidine monophosphate nucleotides, such as UMP, GMP and CMP.
      Levamisole and tetramisole (1 mM), specific inhibitors of alkaline phosphatases,
      did not alter the enzymatic activity. However, a significant inhibition of AMP
      hydrolysis (42%) was observed in the presence of 100 microM alpha,beta-methylene
      ADP, a known inhibitor of ecto-5'-nucleotidase. Since 5'-nucleotidase represents
      the major enzyme responsible for the formation of extracellular adenosine, the
      enzymatic characterization is important to understand its role in purinergic
      systems and the involvement of adenosine in the regulation of neurotransmitter
      release.

PMID- 15465667
TI  - Changes in lipid class and fatty acid composition during development in white
      seabream (Diplodus sargus) eggs and larvae.
AB  - To establish the changes which occur during embryogenesis and early larvae
      development, eggs, yolk-sac larvae (one day old larvae) and absorbed yolk-sac
      larvae (three day old larvae) of white sea bream were examined for lipid class
      and fatty acid composition. The development was characterized by a decrease in
      all lipid classes with the exception of phosphatidylserine (PS) and fatty free
      acids (FFA) which increased, and sphingomyelin (SM) which remained unchanged. The
      changes observed in lipid class content and the decrease in fatty acids in total
      lipid (TL) reflect the utilization and mobilization of lipids during both
      embryogenesis and early larvae development. Fluctuations in the relative
      composition of fatty acids in phosphatidylcholine (PC) during development suggest
      a selective bulk uptake and catabolism of fatty acids in this lipid class. Unlike
      PC, catabolism of triacylglycerol (TG) fatty acid appears to be non-selective.
      During development, the decrease in levels of polyunsaturated fatty acids (PUFA)
      eicosapentaenoic (20:5n-3, EPA) and docosahexaenoic (22:6n-3, DHA) in total lipid
      denotes their utilization as energy substrate by Diplodus sargus larvae.

PMID- 15465668
TI  - The ontogenic development of innate immune parameters of cod (Gadus morhua L.).
AB  - The aim of this study was to monitor the ontogenic development of innate immune
      parameters of cod (Gadus morhua L.) and to determine the presence of maternal
      IgM. The general protein composition and enzyme activity was also studied. At
      intervals, samples were collected of fertilized cod eggs and larvae from 3 days
      after fertilization until 57 days after hatching. Cell lysates were prepared and
      analysed by Western blotting using antibodies prepared against cod IgM, the
      complement component C3 and C-reactive protein (CRP) as well as against cod serum
      proteins and haemoglobin. Antibodies against salmon cathepsins and against
      several mammalian proteins of immunological significance were also used. Maternal
      IgM was not detected but C3 and the closely associated apolipoprotein A-I were
      present from the time of embryo organogenesis. C-reactive protein was not
      detected and none of the antibodies against mammalian immune parameters cross
      reacted with the cod material. Protein and proteomic analysis showed that the
      major proteins of the egg samples were vitellogenin derived maternal proteins.
      Other non-vitellogenin maternal proteins, not yet identified, were also detected
      in the fertilized eggs. Cathepsin was present in all samples, but other enzyme
      activity was restricted to larval samples from 4 days after hatching when feeding
      had commenced. Haemoglobin was not detected until 10 days after hatching.

PMID- 15465669
TI  - Lactose causes heart arrhythmia in the water flea Daphnia pulex.
AB  - The cladoceran Daphnia pulex is well established as a model for ecotoxicology.
      Here, we show that D. pulex is also useful for investigating the effects of
      toxins on the heart in situ and the toxic effects in lactose intolerance. The
      mean heart rate at 10 degrees C was 195.9+/-27.0 beats/min (n=276, range 89.2
      249.2, >80% 170-230 beats/min). D. pulex heart responded to caffeine,
      isoproteronol, adrenaline, propranolol and carbachol in the bathing medium.
      Lactose (50-200 mM) inhibited the heart rate by 30-100% (K(1/2)=60 mM) and
      generated severe arrhythmia within 60 min. These effects were fully reversible by
      3-4 h. Sucrose (100-200 mM) also inhibited the heart rate, but glucose (100-200
      mM) and galactose (100-200 mM) had no effect, suggesting that the inhibition by
      lactose or sucrose was not simply an osmotic effect. The potent antibiotic
      ampicillin did not prevent the lactose inhibition, and two diols known to be
      generated by bacteria under anaerobic conditions were also without effect. The
      lack of effect of l-ribose (2 mM), a potent inhibitor of beta-galactosidase,
      supported the hypothesis that lactose and other disaccharides may affect directly
      ion channels in the heart. The results show that D. pulex is a novel model system
      for studying effects of agonists and toxins on cell signalling and ion channels
      in situ.

PMID- 15465670
TI  - Purification of vitellogenin from smooth flounder (Pleuronectes putnami) and
      measurement in plasma by homologous ELISA.
AB  - Male smooth flounder (Pleuronectes putnami) were induced to produce vitellogenin
      (VTG) by injection of 17beta-estradiol (E2). Anion exchange chromatography of
      precipitated plasma from E2-injected resulted in a single peak consisting of VTG.
      Smooth flounder VTG has an approximate molecular mass of approximately 520 kDa,
      determined by gel filtration with molecular weight standards. Purified VTG was
      used to develop a homologous enzyme-linked immunosorbent assay (ELISA). The
      flounder VTG ELISA is an indirect antigen competition assay with a detection
      limit of 15 ng.ml(-1) and a useful range of 30-950 ng.ml(-1) of diluted sample.
      Intra- and inter-assay precision (as %CV, n=7) ranged from 1.3% to 6.0% and 5.1%,
      respectively. The ELISA was evaluated using plasma samples collected from a
      smooth flounder population captured in the Saint Lawrence Estuary. The ELISA is
      sensitive enough to differentiate males and non-vitellogenic females from
      vitellogenic individuals during early vitellogenesis.

PMID- 15465671
TI  - Isolation and characterisation of renal metabolites of gamma
      glutamylfelinylglycine in the urine of the domestic cat (Felis catus).
AB  - The renal metabolism of the tripeptide, gamma-glutamylfelinylglycine, which our
      group recently identified in the blood of domestic cats (Felis catus), was
      investigated. To test our hypothesis that this unique tripeptide is metabolised
      by the kidney in a similar manner to glutathione-S-conjugates in other animal
      species, [(35)S]cysteine was administered intraperitoneally to an entire male
      cat, and urine collected at 1, 4 and 8 h post-injection. Radiolabelled fractions
      were isolated from the urine following reversed-phase (RP) HPLC. Four
      [(35)S]radiolabelled fractions were identified and characterised by amino acid
      analysis, mass spectrometry and comparison of retention times with synthetic
      compounds (felinine, N-acetyl felinine, felinylglycine, gamma
      glutamylfelinylglycine). In addition to the previously described presence of free
      felinine, we showed the presence of several felinine-containing metabolites,
      including N-acetyl felinine, felinylglycine and unaltered gamma
      glutamylfelinylglycine in cat urine. The results show that renal metabolism of
      gamma-glutamylfelinylglycine in cats, generally occurs in a similar manner to
      glutathione S-conjugates in other animal species, although the detection of
      felinylglycine indicates that subtle differences may exist. Additionally, our
      research indicates that previously reported estimates of felinine excretion in
      male cats need to be increased by as much as 54% to account for other felinine
      containing metabolites in the urine.

PMID- 15465672
TI  - Detection of TIMP-2-like protein in Atlantic cod (Gadus morhua) muscle using two
      dimensional real-time reverse zymography.
AB  - Matrix metalloproteinases (MMPs) have been proposed to participate in postmortem
      degradation of fish muscle connective tissues during storage. In the
      extracellular matrix (ECM) of mammals, a group of specific tissue inhibitors of
      metalloproteinases (TIMPs) contributes in regulating the MMPs present. However,
      little information exists on the presence of TIMPs in fish. In this paper, the
      presence of TIMPs in the muscle of Atlantic cod (Gadus morhua) was investigated
      using gelatin affinity chromatography, real-time reverse zymography (RTRZ) and
      mass spectrometry (MS). Using RTRZ inhibitory action against cod muscle,
      proteinases binding to gelatin were detected in the muscle. The inhibitor had
      similar molecular weight (21 kDa) as a human recombinant TIMP-2 used as a
      reference sample. Because isoforms of TIMP-2 homologues with similar molecular
      weight have been suggested in fish, a two-dimensional RTRZ (2D RTRZ) method was
      designed. The new method showed the existence of only one form with inhibitory
      action against cod muscle proteinases. Finally, de novo sequencing of two
      peptides derived from the cod muscle inhibitor showed high homology to TIMP-2s
      both from human and other teleosts.

PMID- 15465673
TI  - Oxygen-binding modulation of hemocyanin from the slipper lobster Scyllarides
      latus.
AB  - The oxygen-binding properties of hexameric hemocyanin (Hc) from Scyllarides latus
      were investigated with respect to pH, temperature, and modulating effect exerted
      by calcium, lactate, and urate. The oxygen affinity decreased at higher
      temperature, was slightly affected by pH, and was insensitive to lactate.
      Nevertheless, urate markedly increased Hc-oxygen affinity and its temperature
      sensitivity, acting as the physiological major positive effector: four urate
      sites per hexamer with an overall affinity constant of 1 x 10(4) M(-1) were found
      and the exothermic contribution of their binding was found to be about 30 kJ mol(
      1). Calcium ions largely influenced oxygen affinity: their effect, which has an
      opposite sign at low (0-1 mM) and high (0.1-1 M) concentration ranges, indicates
      the presence of two independent types of binding sites with high and low
      affinity, respectively; however, only the former ones seem to be operative in
      vivo because, at physiological calcium concentrations, they are already saturated
      and the oxygen affinity is reduced.

PMID- 15465674
TI  - Characterization and comparison of fatty acyl Delta6 desaturase cDNAs from
      freshwater and marine teleost fish species.
AB  - Fish are the most important dietary source of the n-3 highly unsaturated fatty
      acids (HUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), that have
      particularly important roles in human nutrition reflecting their roles in
      critical physiological processes. The objective of the study described here was
      to clone, functionally characterize and compare expressed fatty acid desaturase
      genes involved in the production of EPA and DHA in freshwater and marine teleost
      fish species. Putative fatty acid desaturase cDNAs were isolated and cloned from
      common carp (Cyprinus carpio) and turbot (Psetta maximus). The enzymic activities
      of the products of these cDNAs, together with those of cDNAs previously cloned
      from rainbow trout (Oncorhynchus mykiss) and gilthead sea bream (Sparus aurata),
      were determined by heterologous expression in the yeast Saccharomyces cerevisiae.
      The carp and turbot desaturase cDNAs included open reading frames (ORFs) of 1335
      and 1338 base pairs, respectively, specifying proteins of 444 and 445 amino
      acids. The protein sequences possessed all the characteristic features of
      microsomal fatty acid desaturases, including three histidine boxes, two
      transmembrane regions, and N-terminal cytochrome b(5) domains containing the haem
      binding motif, HPGG. Functional expression showed all four fish cDNAs encode
      basically unifunctional Delta6 fatty acid desaturase enzymes responsible for the
      first and rate-limiting step in the biosynthesis of HUFA from 18:3n-3 and 18:2n
      6. All the fish desaturases were more active towards the n-3 substrate with
      59.5%, 31.5%, 23.1% and 7.0% of 18:3n-3 being converted to 18:4n-3 in the case of
      turbot, trout, sea bream and carp, respectively. The enzymes also showed very
      low, probably physiologically insignificant, levels of Delta5 desaturase
      activity, but none of the products showed Delta4 desaturase activity. The cloning
      and characterization of desaturases from these fish is an important advance, as
      they are species in which there is a relative wealth of data on the nutritional
      regulation of fatty acid desaturation and HUFA synthesis, and between which
      substantive differences occur.

PMID- 15465676
TI  - Sexual maturation and related changes in aspartate transcarbamylase activity of
      gonad tissues in the soft shell clam (Mya arenaria).
AB  - The information on the relation between the gonadal aspartate transcarbamylase
      (ACTase) activity and the sexual maturation in molluscs is very fragmentary and
      is still absent in Mya arenaria. The determination of ATCase activity, energy
      reserves levels and maturation stages were done in gonads of clams. Results
      showed that the seasonal cycle of storage and utilization of energy reserves in
      gonads of clams are linked to the bimodal reproduction well known in this
      bivalve. ATCase activity was high in clams at development and ripe stages, while
      this activity was low for individuals found in indifferent, spawning or spent
      stages. This difference can be explained by the fact that during gonad
      development, gonadal synthetic activity increased following the mitotic events
      associated to the reproductive cycle. The results presented in this paper have
      confirmed the link between ATCase activity and gametogenesis in M. arenaria.
      Further work should be realized in order to assess if ATCase activity could be
      considered as a potential biomarker to evaluate the disruption of sexual
      maturation in clams collected in sites such as the St. Lawrence estuary.

PMID- 15465675
TI  - Expression of guanylyl cyclase genes in medaka hybrids (Oryzias curvinotus x
      Oryzias latipes).
AB  - The Hong Kong-originated medaka fish Oryzias curvinotus expresses nine genes
      (OcGC1 approximately OcGC8 and OcGC-R2) for membrane guanylyl cyclases (membrane
      GCs) and three genes (OcGCS-alpha(1), OcGCS-alpha(2), and OcGCS-beta(1)) for
      soluble GC subunits. The deduced amino acid sequences of membrane GCs expressed
      in O. curvinotus were quite similar to those expressed in the Japanese medaka
      Oryzias latipes, including a novel membrane GC gene, OlGC8, first isolated and
      characterized in O. latipes. O. curvinotus was able to produce hybrids with O.
      latipes, irrespective of the direction of crossing, and the resulting hybrids
      expressed both maternal and paternal soluble GC subunit genes, suggesting the
      possibility of the formation of a chimeric heterodimer in the hybrids. However,
      in early embryogenesis of hybrids, the maternal soluble GC subunit genes were
      expressed earlier than the paternal soluble GC subunit genes, suggesting that the
      maternal soluble GC subunit genes interact more effectively with maternal
      effector molecules such as transcription factors than with those of paternal
      origin.

PMID- 15465677
TI  - Biochemical dynamics of spermatogenesis and oogenesis in Eledone cirrhosa and
      Eledone moschata (Cephalopoda: Octopoda).
AB  - The effect of spermatogenesis and oogenesis on protein, lipid, glycogen,
      cholesterol and energy contents, total amino acid and fatty acid profiles of
      Eledone cirrhosa and Eledone moschata tissues (gonad, digestive gland and muscle)
      was investigated. A significant (p<0.05) increase in the amino acids and protein
      content of the gonad throughout sexual maturation (namely in oogenesis) was
      observed, but the allocation of these nitrogen compounds from the digestive gland
      and muscle was not evident. The major essential amino acids (EAA) in the three
      tissues were leucine, lysine and arginine. The major nonessential amino acids
      (NEAA) were glutamic acid, aspartic acid and alanine. A significant increase in
      lipid and fatty acid contents of gonad and digestive gland was observed. There
      was also little evidence of accumulated lipid storage reserves being used for egg
      production. It seems that for egg production Eledone species use energy directly
      from food, rather than from stored products. Most of saturated fatty acid (SFA)
      content of the three tissues was presented as 16:0 and 18:0, monounsaturated
      fatty acid (MUFA) content as 18:1 and 20:1 and polyunsaturated fatty acid (PUFA)
      content as 20:4n-6, 20:5n-3 and 22:6n-3. Cholesterol and glycogen contents
      significantly increased in gonad and digestive gland throughout maturation while
      the muscle revealed no obvious pattern. If Eledone's component sterols are of a
      dietary origin, a considerable variation in the cholesterol content between
      species might be expected on the basis of the sterol composition of their prey.
      Although spermatogenesis and oogenesis had a significant effect (p<0.05) in gonad
      and digestive gland energy content, the biochemical composition of digestive
      gland and muscle may not be primarily influenced by sexual maturation, but rather
      by other biotic factors such as feeding activity, food availability, spawning and
      brooding.

PMID- 15465678
TI  - Plant science in the age of phage.

PMID- 15465679
TI  - Death proteases come alive.

PMID- 15465680
TI  - Does the oxidative stress used by plants for defence provide a source of
      nutrients for pathogenic fungi?

PMID- 15465681
TI  - Two forms of cytochrome c6 in a single eukaryote.

PMID- 15465682
TI  - Genome-scale data, angiosperm relationships, and "ending incongruence": a
      cautionary tale in phylogenetics.
AB  - As systematists grapple with assembling the Tree of Life, recent studies have
      encouraged a genomic-scale approach, obtaining DNA sequence data for entire
      nuclear, plastid or mitochondrial genomes for a few exemplar taxa. Some have
      proclaimed that this comparative genomic strategy heralds the end of incongruence
      in phylogeny reconstruction. Although we applaud the use of many genes to resolve
      phylogenetic patterns, there is a significant caveat. In spite of, or even
      because of, the abundant data per taxon, whole-genome sequencing for a few
      exemplars can provide completely resolved and strongly supported, but incorrect,
      evolutionary reconstructions. We provide a conspicuous example that includes
      Amborella, the putative sister of all other extant angiosperms, highlighting the
      limits of phylogenetics when whole genomes are used but taxon sampling is poor.

PMID- 15465683
TI  - Cytoplasmic/nuclear plant lectins: a new story.

PMID- 15465684
TI  - Reactive oxygen gene network of plants.

PMID- 15465685
TI  - Shaping the shoot: a circuitry that integrates multiple signals.

PMID- 15465686
TI  - More than a yolk: the short life and complex times of the plant endosperm.

PMID- 15465687
TI  - An alternative approach to social capital: exploring the linkage between health
      consciousness and community participation.
AB  - In recent years, social capital has received a great deal of attention in health
      communication. The fundamental premise behind the increased attention to social
      capital is the positive health outcome of social capital. Social capital is
      treated as an antecedent to health. Building on recent research that points out
      the role of trait-level variables in the production of social capital, this
      article examines the role of health consciousness in the production of social
      capital. The central idea here is that health conscious individuals choose to
      participate in their communities because of the positive health benefits of such
      participation.

PMID- 15465688
TI  - Scientese and ambiguous citations in the selling of unproven medical treatments.
AB  - Unproven medical treatments are widely marketed, and are especially accessible
      via the Internet. Little is known about factors that may increase the
      persuasiveness of information used to promote such unproven treatments. This
      article examines the effect of scientese (use of scientific jargon) and
      attributed versus unattributed citations on message persuasiveness on science and
      nonscience majors. Scientese, as expected, increased message persuasiveness.
      Contrary to expectations, this effect was not moderated by science versus
      nonscience major, graduate versus undergraduate status, or potential involvement
      with the message topic. In addition, no effect was found for attributed versus
      unattributed citations either as a main effect or in interaction with science
      major, graduate or undergraduate status, or for an indicator of involvement with
      the health topic. These findings are consistent with Food and Drug Administration
      concerns about the ability of the public to critically discern the quality of
      evidence supporting use of unproven remedies and dietary supplements. Similarly,
      they raise questions about the judicial reasoning that presumes consumers can
      make such judgments, though replication with clinical populations would be
      desirable to strengthen policy-relevant inferences.

PMID- 15465689
TI  - The effect of family and peer communication on college students' communication
      with dating partners about HIV and AIDS.
AB  - As family and peers are primary socializing agents in the lives of young adults,
      a social learning based model of communication about HIV/AIDS among dating
      partners was developed and tested, examining the role of interactions with family
      and peers in this type of communication. Specifically, the model describes
      relationships between general communication, communication about sexuality, and
      communication about HIV/AIDS with parents, peers, and dating partners.
      Participants were 153 young adult couples who completed measures of their
      communication practices, as well as their communication with family and peers.
      Communication practices in the family of origin appear to influence both general
      communication and communication about HIV/AIDS with dating partners.
      Communication practices with peers influenced general communication,
      communication about sexuality, and communication about HIV/AIDS with dating
      partners. Participants and their dating partners exhibited relative agreement
      about their general communication practices and their communication about
      HIV/AIDS, but showed less agreement in reports of their communication about
      sexuality. Implications for understanding the role of family and peer
      interactions in communication about HIV/AIDS with dating partners are discussed.

PMID- 15465690
TI  - Assessing the Get Real about Violence curriculum: process and outcome evaluation
      results and implications.
AB  - Guided largely by the theory of reasoned action, the Get Real about Violence
      curriculum attempts to reduce verbal and physical aggression, as well as
      behaviors that encourage verbal or physical aggression, such as watching a fight
      and spreading rumors about a fight that is going to happen. This 12-lesson
      curriculum was evaluated using a pretest-posttest control group design.
      Participants were 293 seventh-grade boys and girls enrolled in two public junior
      high schools in a moderate size Midwestern city. The curriculum had its greatest
      effect on verbal aggression, where the experimental school outperformed the
      control school on three of four variables, including behavior, behavioral intent,
      and attitudes. The experimental school also outperformed the control school in
      several other instances, including intent to watch a fight, intent to spread
      rumors about a fight, and beliefs and opinions about fighting and violence in
      general. Implications for the Get Real about Violence curriculum, and for youth
      violence prevention and intervention programs are discussed.

PMID- 15465691
TI  - Enacting "health communication": the field of health communication as constructed
      through publication in scholarly journals.
AB  - Based on an analysis of articles in health communication journals and in
      regional, national, and international communication journals, this study
      identifies publication trends and research priorities for health communication
      articles in the 1990s and the year 2000. Based on a content analysis of article
      abstracts, researchers determined the extent to which health communication
      articles appeared in various journals as well as the emphasis on specific topics
      in health communication research, methodological approaches, and theoretical
      frameworks. The article concludes with reflections on the implications of this
      study for future work in the area of health communication.

PMID- 15465692
TI  - Reaching unhealthy eaters: applying a strategic approach to media vehicle choice.
AB  - Founded upon the argument that unhealthy eaters need to be reached through
      strategic choices that are driven by adequate formative research, this article
      examines the media consumption patterns of unhealthy eaters. Based on an analysis
      of the 1999 Lifestyle data, the article points out that healthy and unhealthy
      eaters differ systematically in their media choices. While television news is the
      most effective channel for reaching healthy eaters, television sports and
      entertainment-oriented Internet are the two major media categories consumed by
      the unhealthy eater. Also, healthy eaters are more likely to be drawn to print
      media, suggesting that print-based healthy eating campaigns are unlikely to reach
      the at-risk group. The article recommends the exploration of alternative
      entertainment-oriented channels and content strategies to effectively reach the
      unhealthy eater.

PMID- 15465693
TI  - Bibliography.

PMID- 15465694
TI  - Regulation of nitrate uptake at the whole-tree level: interaction between
      nitrogen compounds, cytokinins and carbon metabolism.
AB  - Pedospheric nitrate uptake is closely integrated with the nitrogen (N) status and
      demand of the whole tree. Signaling substances communicating the N demand of the
      shoot to the roots are required in an integrated regulatory system. Besides
      phloem mobility, such signal compounds must have the potential to repress or
      increase nitrate uptake either at the transcriptional or post-transcriptional
      level. Amino compounds cycling within the tree are involved in the regulation of
      nitrate uptake. In many tree species, inorganic N is generally assimilated in
      roots, and amino acids--the direct products of N assimilation--are transported in
      the xylem to the sites of N demand. If the quantity of amino acids transported to
      the above-ground parts of the tree exceeds shoot N demand, some amino compounds
      are reallocated to the roots by phloem transport. Particular amino compounds
      exert transcriptional and post-transcriptional control over nitrate uptake by
      roots. Induction of nitrate transporters is mediated by nitrate or nitrite, or
      both, and possibly also by cytokinins, which cycle within the tree and act as
      both root-to-shoot and shoot-to-root signals. This review focuses on tree
      specific requirements for N regulation and signaling, as well as the link between
      carbon metabolism and nitrate uptake.

PMID- 15465695
TI  - Detection of tree roots and determination of root diameters by ground penetrating
      radar under optimal conditions.
AB  - A tree's root system accounts for between 10 and 65% of its total biomass, yet
      our understanding of the factors that cause this proportion to vary is limited
      because of the difficulty encountered when studying tree root systems. There is a
      need to develop new sampling and measuring techniques for tree root systems.
      Ground penetrating radar (GPR) offers the potential for direct nondestructive
      measurements of tree root biomass and root distributions to be made. We tested
      the ability of GPR, with 500 MHz, 800 MHz and 1 GHz antennas, to detect tree
      roots and determine root size by burying roots in a 32 m3 pit containing damp
      sand. Within this test bed, tree roots were buried in two configurations: (1)
      roots of various diameters (1-10 cm) were buried at a single depth (50 cm); and
      (2) roots of similar diameter (about 5 cm) were buried at various depths (15-155
      cm). Radar antennas were drawn along transects perpendicular to the buried roots.
      Radar profile normalization, filtration and migration were undertaken based on
      standard algorithms. All antennas produced characteristic reflection hyperbolas
      on the radar profiles allowing visual identification of most root locations. The
      800 MHz antenna resulted in the clearest radar profiles. An unsupervised, maximum
      convexity migration algorithm was used to focus information contained in the
      hyperbolas back to a point. This resulted in a significant gain in clarity with
      roots appearing as discrete shapes, thereby reducing confusion due to overlapping
      of hyperbolas when many roots are detected. More importantly, parameters
      extracted from the resultant waveform through the center of a root correlated
      well with root diameter for the 500 MHz antenna, but not for the other two
      antennas. A multiple regression model based on the extracted parameters was
      calibrated on half of the data (R2 = 0.89) and produced good predictions when
      tested on the remaining data. Root diameters were predicted with a root mean
      squared error of 0.6 cm, allowing detection and quantification of roots as small
      as 1 cm in diameter. An advantage of this processing technique is that it
      produces results independently of signal strength. These waveform parameters
      represent a major advance in the processing of GPR profiles for estimating root
      diameters. We conclude that enhanced data analysis routines combined with
      improvements in GPR hardware design could make GPR a valuable tool for studying
      tree root systems.

PMID- 15465696
TI  - Root distribution of Pinus pinaster, P. radiata, Eucalyptus globulus and E.
      kochii and associated soil chemistry in agricultural land adjacent to tree lines.
AB  - We quantified the extent and distribution of roots of four commonly planted tree
      species (Eucalyptus globulus Labill., Pinus radiata D. Don, P. pinaster Aiton and
      E. kochii Maiden & Blakely subsp. plenissima C.A. Gardner) in agricultural land
      adjacent to tree lines, and examined the effect of soil type and root pruning on
      root morphology. Root distribution in soil adjacent to tree lines was mapped by a
      trench profile method at 13 sites on the south coast of Western Australia. Soil
      samples were collected to determine water content and fertility. The lateral
      extent of tree roots ranged from 10 m for E. kochii to 44 m for P. pinaster. This
      equated to between 1.5 and 2.5 times tree height (H) for E. globulus and Pinus
      spp. to 4H for E. kochii. Root density declined logarithmically with distance
      from the trees and was greatest for P. pinaster and least for E. globulus (P <
      0.001). The rate of decrease in root density with distance from the trees was
      greatest for the Pinus spp. and least for E. kochii (P < 0.05). Root density was
      generally greatest in the top 0.5 m of the soil profile and decreased with
      increasing depth. This decrease was relatively gradual in the deep sands, but
      abrupt in clay subsoil. Root dry mass in the sandy top soil beyond 0.5H ranged
      between 1.0 and 55.5 Mg km(treeline) (-1) for 6-year-old E. kochii and 50-year
      old P. pinaster, respectively. Soil water content generally increased with
      distance from the trees (P < 0.001). There was no evidence of reduced soil
      fertility in the top 1.4 m of the soil profile adjacent to the trees. Two to four
      years after trees had been root pruned, both the lateral extent and vertical
      distribution of roots were similar for pruned and unpruned trees. The density of
      roots < 2 mm in diameter was greater for root-pruned trees than for unpruned
      trees (P < 0.05). We conclude that the study species can compete with
      agricultural crops based on the lateral extent of their roots and the occurrence
      of greatest root density within 0.5 m of the soil surface.

PMID- 15465697
TI  - Carbon allocation and nitrogen acquisition in a developing Populus deltoides
      plantation.
AB  - We established Populus deltoides Bartr. stands differing in nitrogen (N)
      availability and tested if: (1) N-induced carbon (C) allocation could be
      explained by developmental allocation controls; and (2) N uptake per unit root
      mass, i.e., specific N-uptake rate, increased with N availability. Closely spaced
      (1 x 1 m) stands were treated with 50, 100 and 200 kg N ha(-1) year(-1) of time
      release balanced fertilizer (50N, 100N and 200N) and compared with unfertilized
      controls (0N). Measurements were made during two complete growing seasons from
      May 1998 through October 1999. Repeated nondestructive measurements were carried
      out to determine stem height and diameter, leaf area and fine-root dynamics. In
      October of both years, above- and belowground biomass was harvested, including
      soil cores for fine-root biomass. Leaves were harvested in July 1999. Harvested
      tissues were analyzed for C and N content. Nondestructive stem diameter and and
      fine-root dynamic measurements were combined with destructive harvest data to
      estimate whole-tree biomass and N content at the end of the year, and to estimate
      specific N-uptake rates during the 1999 growing season. Shoot growth response was
      greater in fertilized trees than in control trees; however, the 100N and 200N
      treatments did not enhance growth more than the 50N treatment. Root biomass
      proportions decreased over time and with increasing fertilizer treatment.
      Fertilizer-induced changes in allocation were explained by accelerated
      development. Specific N-uptake rates increased during the growing season and were
      higher for fertilized trees than for control trees.

PMID- 15465698
TI  - In situ measurement of water absorption by fine roots of three temperate trees:
      species differences and differential activity of superficial and deep roots.
AB  - The spatial heterogeneity of water uptake by fine roots under field conditions
      was analyzed in situ with miniature sap flow gauges in a mature beech-oak-spruce
      mixed stand. Sap flow rate (J), sap flow density (Jd), and root surface-area
      specific flow rate (uptake rate, Js) were measured for eight to 10 small-diameter
      roots (3-4 mm) per species in the organic layer (superficial roots) and in the
      mineral soil (30-80 cm, deep roots) during four months in summer 1999. We
      calculated Js by relating J to the surface area of the section of the fine root
      system distal to the position of the gauge on the root. When measured
      synchronously, roots of the three species did not differ significantly in mean
      Js, although oak roots tended to have lower rates. However, Jd decreased in the
      sequence spruce > beech > oak in most measurement periods. Microscopic
      investigation revealed differences in fine root anatomy that may partly explain
      the species differences in Jd and Js. Oak fine roots had a thicker periderm than
      beech and spruce roots of similar diameter and spruce roots had fewer fine branch
      rootlets than the other species. Synchronously recorded Jd and Js of nearby roots
      of the same tree species showed large differences in flow with coefficients of
      variation from 25 to 150% that could not be explained by patchy distribution of
      soil water. We hypothesize that the main cause of the large spatial heterogeneity
      in root water uptake is associated with differences between individual roots in
      morphology and ultrastructure of the root cortex that affect root radial and root
      soil interface conductivities. The high intraspecific variation in Js may mask
      species differences in root water uptake. Superficial roots of all species
      typically had about five times higher Jd than deep roots of the same species.
      However, Js values were similar for superficial and deep roots in beech and
      spruce because small diameter roots of both species were more branched in the
      organic layer than in mineral soil. In oak, deep roots had lower Js (maximum of
      100 g m(-2) day(-1)) than superficial roots (about 1000 g m(-2) day(-1)). We
      conclude that temperate tree species in mixed stands have different water uptake
      capacities. Water flow in the rhizosphere of forests appears to be a highly
      heterogeneous process that is influenced by both tree species and differences in
      uptake rates of individual roots within a species.

PMID- 15465699
TI  - Allocation of 14C-carbon in two species of larch seedlings infected with
      ectomycorrhizal fungi.
AB  - The flow of labeled carbon in ectomycorrhizal and non-ectomycorrhizal seedlings
      of Japanese larch (Larix kaempferi Sarg.) and its F1 hybrid (Larix gmelinii Rupr.
      x L. kaempferi) was studied. Larch seedlings were grown in a greenhouse for 110
      days with larch forest soil (FM) or Suillus grevillei (SM) inoculum, or in the
      absence of ectomycorrhizal fungi (NM). Shoots of colonized and NM seedlings were
      exposed to a pulse of 14CO2 for 1 h under natural light. Seedlings were harvested
      following 0, 6 and 24 h of exposure to 14CO2. At the final harvest, SM seedlings
      of Japanese larch and hybrid larch allocated 2.6 and 2.5% more 14C, respectively,
      to roots than NM seedlings. In contrast, FM seedlings of Japanese larch and
      hybrid larch allocated 6.5 and 18.0% more 14C, respectively, to the stem than NM
      seedlings. Of the total 14C detected in needle, stem and root fractions, FM and
      SM seedlings allocated a greater proportion than NM seedlings, perhaps because FM
      and SM seedlings had significantly (P < 0.05) higher photosynthetic rates than NM
      seedlings. As a result, FM and SM seedlings had greater dry masses than NM
      seedlings. Concentrations of nitrogen and phosphorus in FM and SM seedlings were
      significantly (P < 0.05) higher than in NM seedlings, as was stomatal
      conductance.

PMID- 15465700
TI  - Characterization, expression and evolution of two novel subfamilies of Pinus
      monticola cDNAs encoding pathogenesis-related (PR)-10 proteins.
AB  - Proteins of the pathogenesis-related (PR)-10 family are induced in many plants by
      phytopathogens and environmental stresses. A multi-gene family of PR10 proteins
      has previously been found in the genome of western white pine (Pinus monticola
      Dougl. ex D. Don). We isolated two novel subfamilies of PR10 cDNAs (PmPR10-2 and
      PmPR10-3) from P. monticola that are distinct from other PR10 genes (PmPR10-1.1
      1.14) reported from the same species. The PmPR10 proteins are grouped in three
      subfamilies based on similarity in amino acid sequences. The sequence identities
      of PmPR10 proteins are much higher among members within a subfamily than among
      members of different subfamilies (86-99% versus 59-68%). Induction of both PmPR10
      2 and PmPR10-3 mRNAs was detected by reverse transcriptase-polymerase chain
      reaction (RT-PCR) in needles in response to wounding treatment. PmPR10-3 was also
      expressed in needles during cold acclimation in winter. Transcript levels of both
      PmPR10-2 and PmPR10-3 were less than the detectable levels of constitutive
      expression in roots, stems and vegetative shoots, whereas PmPR10-1.10 mRNA of
      subfamily I was expressed at various levels. Phylogenetic analysis showed that
      PmPR10 and PR10 proteins from other conifers are grouped within one clade that is
      distinct from that of angiosperm PR10 proteins. In the conifer monophyletic
      group, PR10 sequences diversify into three distinct clusters. Among these three
      clusters, some PR10 proteins from single conifer species showed greater
      divergence distances than sequences from other conifer species, suggesting that,
      within the conifers, the multi-gene family underwent great diversification during
      evolution. Based on ratios of nonsynonymous to synonymous nucleotide
      substitutions (Ka/Ks), we speculate that positive selection resulted in the
      divergence of PmPR10 subfamilies I and III. Possible mechanisms and significance
      of PR10 gene evolution are discussed.

PMID- 15465701
TI  - Contribution of root respiration to soil surface CO2 flux in a boreal black
      spruce chronosequence.
AB  - We quantified the contributions of root respiration (RC) and heterotrophic
      respiration to soil surface CO2 flux (RS) by comparing trenched and untrenched
      plots in well-drained and poorly drained stands of a black spruce (Picea mariana
      (Mill.) BSP) fire chronosequence in northern Manitoba, Canada. Our objectives
      were to: (1) test different equations for modeling RS as a function of soil
      temperature; and (2) model annual RS and RC for the chronosequence from
      continuous soil temperature measurements. The choice of equation to model RS
      strongly affected annual RS and RC, with an Arrhenius-based model giving the best
      fit to the data, especially at low temperatures. Modeled values of annual RS were
      positively correlated with soil temperature at 2-cm depth and were affected by
      year of burn and trenching, but not by soil drainage. During the growing season,
      measured RC was low in May, peaked in late July and declined to low values by the
      end of the growing season. Annual RC was < 5% of RS in the recently burned
      stands, approximately 40% in the 21-year-old stands and 5-15% in the oldest (152
      year-old) stands. Evidence suggests that RC may have been underestimated in the
      oldest stands, with residual root decay from trenching accounting for 5-10% of
      trenched plot RS at most sites.

PMID- 15465702
TI  - Regulation of organic and inorganic nitrogen uptake in Scots pine (Pinus
      sylvestris) seedlings.
AB  - Plants possess regulatory mechanisms that enhance nitrogen (N) uptake under
      conditions of spatial and temporal variation in N availability. Study of
      regulatory mechanisms has focused almost exclusively on the uptake of inorganic N
      sources (i.e., ammonium (NH4+), nitrate (NO3-). Several lines of evidence,
      however, suggest that amino acids may constitute a potential source of N for a
      number of plant species, including conifers. In the present study, we
      investigated the uptake of amino acids and inorganic N in Scots pine (Pinus
      sylvestris L.) seedlings grown at different N concentrations. We compared the
      uptake rate of the individual N sources using U-[13C2], [15N]-glycine, U-[13C6],
      [15N4]-arginine, 15NH4, or 15NO3, and tested the short-term effect of N supply on
      the uptake rate of glycine, arginine and in field-grown Scots pine seedlings. Our
      data indicate that Scots pine seedlings can absorb substantial amounts of N in
      the form of intact arginine and glycine molecules. The data also suggest that
      Scots pine seedlings down-regulate their uptake of NH4+-N and arginine-N, but not
      of glycine-N in response to increased endogenous N concentrations.

PMID- 15465703
TI  - Are wetlands the reservoir for avian cholera?
AB  - Wetlands have long been suspected to be an important reservoir for Pasteurella
      multocida and therefore the likely source of avian cholera outbreaks. During the
      fall of 1995-98 we collected sediment and water samples from 44 wetlands where
      avian cholera epizootics occurred the previous winter or spring. We attempted to
      isolate P. multocida in sediment and surface water samples from 10 locations
      distributed throughout each wetland. We were not able to isolate P. multocida
      from any of the 440 water and 440 sediment samples collected from these wetlands.
      In contrast, during other investigations of avian cholera we isolated P.
      multocida from 20 of 44 wetlands, including 7% of the water and 4.5% of the
      sediment samples collected during or shortly following epizootic events. Our
      results indicate that wetlands are an unlikely reservoir for the bacteria that
      causes avian cholera.

PMID- 15465704
TI  - Epizootiology of an epizootic hemorrhagic disease outbreak in West Virginia.
AB  - An outbreak of epizootic hemorrhagic disease virus, serotype 2 (EHDV-2) was
      responsible for localized white-tailed deer (Odocoileus virginianus) mortality in
      Hardy and Hampshire counties, West Virginia (USA), in the summer and fall of
      1993. Using available historical data on regional herd immunity, data
      opportunistically collected during the epizootic, and postepizootic sampling of
      hunter-harvested deer, we grossly estimate certain epidemiologic parameters and
      compare findings to a hypothesis about hemorrhagic disease outbreaks in the
      Appalachian Mountains. During the epizootic, 57.9 km(2) were actively searched
      and 228 dead deer were found. Epizootic hemorrhagic disease virus, serotype 2 was
      isolated from seven of nine deer sampled in Hardy and Hampshire counties.
      Preepizootic exposure of deer to EHD viruses was unknown, but available data
      suggest that it was negligible. The geographic distribution of the outbreak was
      defined by plotting the locations of dead deer found during the outbreak, as well
      as the locations of deer harvested by hunters after the outbreak that had
      antibodies to EHDV-2 on a map sectioned into 16.65 km(2) rectangular sections.
      Sections that included one or more dead deer or hunter-harvested deer with
      antibodies to EHDV-2 were included in the defined outbreak area. Postoutbreak
      sampling revealed monospecific EHDV-2 antibodies in 12% of deer harvested by
      hunters within the defined outbreak area. Based on the available data and
      accepting certain assumptions, gross calculations suggest that this outbreak
      appears to have been isolated and probably killed a high percentage of the deer
      that were infected. This is consistent with the hypothesis that sporadic
      hemorrhagic disease outbreaks in the Appalachian Mountains are usually localized
      and severe.

PMID- 15465705
TI  - Antibodies to Aleutian mink disease parvovirus in free-ranging European mink
      (Mustela lutreola) and other small carnivores from southwestern France.
AB  - Owing to the rapid decline of the European mink (Mustela lutreola) in France, a
      national conservation action plan has been initiated, in which scientific
      research to improve understanding of the causes of the decline is one of the
      primary objectives. In order to investigate the possible role of Aleutian disease
      parvovirus (ADV) in decline of the species, a serologic survey was conducted from
      March 1996 to March 2002 in 420 free-ranging individuals of six species of small
      carnivores distributed in eight departments of southwestern France. Antibodies to
      ADV were detected in 17 of 75 American mink (Mustela vison), 12 of 99 European
      mink, 16 of 145 polecats (Mustela putorius), four of 17 stone martens (Martes
      foina), one of 16 pine martens (Martes martes), and three of 68 common genets
      (Genetta genetta). Seroprevalence was significantly higher in American mink than
      in other species. Seropositive individuals with gamma globulin levels >20% were
      observed in four European mink, four American mink, two stone martens, and one
      pine marten. Geographic distribution of positive animals indicates the virus has
      spread to all areas where European mink are found. Furthermore, a trend of
      increasing prevalence seems to appear in Mustela sp. sympatric with American
      mink. Although further investigations are necessary to evaluate the role of ADV
      in decline of European mink, evidence of the virus in the wild at the levels
      found in our study has implications for conservation of this species.

PMID- 15465706
TI  - Rabies in a captive colony of big brown bats (Eptesicus fuscus).
AB  - Our research has focused on the ecology of commensal populations of big brown
      bats (Eptesicus fuscus) in Fort Collins, Colorado (USA), in relation to rabies
      virus (RV) transmission. We captured 35 big brown bats (Eptesicus fuscus) in late
      summer 2001 and held them captive for 4.8 mo. The bats were initially placed in
      an indoor cage for 1 mo then segregated into groups of two to six per cage. Two
      of the bats succumbed to rabies virus (RV) within the first month of capture.
      Despite group housing, all of the remaining bats were healthy over the course of
      the investigation; none developed rabies, although one of the rabid bats was
      observed to bite her cage mates. Reverse transcription-polymerase chain reaction
      (RT-PCR) and Taqman real-time PCR analysis of the RNA derived from the brain
      tissue, salivary glands, and oral swab samples confirmed RV infection in the dead
      bats. Rabies virus was also isolated from the brain tissue upon passage in mouse
      neuroblastoma cells. Nucleotide sequence analysis of the RV nucleoprotein (N)
      gene showed 100% identity with the N gene sequence of a 1985 E. fuscus isolate
      from El Paso County, Colorado. Bat sera obtained six times throughout the study
      were assayed for RV neutralizing antibodies using the rapid fluorescent focus
      inhibition test. The RV neutralizing activity in the serum was associated with
      the IgG component, which was purified by binding to protein G Sepharose. Five
      bats were RV seropositive prior to their capture and maintained titers throughout
      captivity. Two adult bats seroconverted during captivity. Two volant juvenile
      bats had detectable RV antibody titers at the first serum collection but were
      negative thereafter. Four seronegative bats responded to a RV vaccine
      administration with high titers of RV antibodies. A serologic survey of big brown
      bats in the roost from which one of the captive rabid bats had originated showed
      a significant rise in seroprevalence during 2002.

PMID- 15465707
TI  - Prevalence of neurotoxic Clostridium botulinum type C in the gastrointestinal
      tracts of tilapia (Oreochromis mossambicus) in the Salton Sea.
AB  - Tilapia (Oreochromis mossambicus) have been implicated as the source of type C
      toxin in avian botulism outbreaks in pelicans (Pelecanus erythrorhynchos,
      Pelecanus occidentalis californicus) at the Salton Sea in southern California
      (USA). We collected sick, dead, and healthy fish from various sites throughout
      the Sea during the summers of 1999 through 2001 and tested them for the presence
      of Clostridium botulinum type C cells by polymerase chain reaction targeting the
      C(1) neurotoxin gene. Four of 96 (4%), 57 of 664 (9%), and five of 355 (1%)
      tilapia tested were positive for C. botulinum type C toxin gene in 1999, 2000,
      and 2001, respectively. The total number of positive fish was significantly
      greater in 2000 than in 2001 (P<0.0001). No difference in numbers of positives
      was detected between sick and dead fish compared with live fish. In 2000, no
      significant relationships were revealed among the variables studied, such as
      location and date of collection.

PMID- 15465708
TI  - A DNA-based assay identifies Batrachochytrium dendrobatidis in amphibians.
AB  - Chytridiomycosis caused by Batrachochytrium dendrobatidis (Chytridiomycota) has
      been implicated in declines of amphibian populations on four continents. We have
      developed a sensitive and specific polymerase chain reaction-based assay to
      detect this pathogen. We isolated B. dendrobatidis from captive and wild
      amphibians collected across North America and sequenced the internal transcribed
      spacer regions of the rDNA cassette of multiple isolates. We identified two
      primers (Bd1a and Bd2a) that are specific to B. dendrobatidis under amplification
      conditions described in this study. DNA amplification with Bd1a/Bd2a primers
      produced a fragment of approximately 300 bp from B. dendrobatidis DNA but not
      from DNA of other species of chytrids or common soil fungi. The assay detected 10
      zoospores or 10 pg of DNA from B. dendrobatidis and detected infections in skin
      samples from a tiger salamander (Ambystoma tigrinum), boreal toads (Bufo boreas),
      Wyoming toads (Bufo baxteri), and smooth-sided toads (Bufo guttatus). This assay
      required only small samples of skin and can be used to process a large number of
      samples.

PMID- 15465709
TI  - Safety of Brucella abortus strain RB51 in black bears.
AB  - In two studies conducted from October 1999 to March 2000 and December 2000 to
      April 2001, adult black bears (Ursus americanus) were orally inoculated with 1.4
      3.1 x 10(10) colony-forming units (CFU) of Brucella abortus strain RB51 (SRB51,
      n=12) or 2 ml of 0.15 M NaCl solution (saline, n=11). We did not detect a
      difference (P>0.05) in antibody titers to SRB51 in serum obtained before
      vaccination, at 8 wk after vaccination, or at necropsy at 21 or 23 wk after
      vaccination between SRB51-vaccinated and nonvaccinated bears. The SRB51 vaccine
      strain was recovered from tissues obtained at necropsy from one of six SRB51
      vaccinated bears in study 1, but none of the six SRB51-vaccinated bears in study
      2. Vaccination of black bears with SRB51 did not appear to influence (P>0.05)
      reproductive performance.

PMID- 15465710
TI  - Evaluation of ivermectin for treatment of hair loss syndrome in black-tailed
      deer.
AB  - Since 1997, numerous Columbian black-tailed deer (Odocoileus hemionus
      columbianus) in western Washington (USA) have developed a hair loss syndrome that
      often preceded emaciation, debilitation, pneumonia, and death. To study this
      syndrome, eight affected free-ranging Columbian black-tailed deer fawns were
      captured from western Washington in February 1999 to determine the effect of
      ivermectin treatment. Fecal examinations indicated that the internal parasites
      were Dictyocaulus viviparus, Parelaphostrongylus sp., Trichuris sp., Moniezia
      sp., Eimeria spp., and gastrointestinal strongyles. Biting lice (Tricholipeurus
      parallelus) were observed on all deer, with up to 5 lice/cm(2) on the index areas
      counted. Three deer were treated with ivermectin subcutaneously at doses between
      0.2 and 1.3 mg/kg of body weight monthly for four consecutive months, and five
      control deer received no anthelmintic treatment. Complete blood counts, parasite
      evaluations, weight gains, and hair loss evaluations were used to assess
      effectiveness of treatment. Two untreated deer died during the experiment
      compared with no deaths among the three treated deer. Treated deer gained
      significantly more weight (P<0.05) than the untreated deer (22.4 vs. 12.6 kg,
      respectively) that survived the experiment, had significantly fewer parasite eggs
      and larvae (P<0.05) in feces and significantly fewer nematodes (P<0.05) at
      necropsy, and regrew their hair at a faster rate than untreated deer. Lice and
      all nematode eggs and larval stages in feces were eliminated or greatly reduced
      following treatment. On the basis of these data, excessive louse populations,
      gastrointestinal nematodes, and the lung-worms Parelaphostrongylus sp. and D.
      viviparus, might be important predisposing factors for this hair loss condition
      and death of affected animals.

PMID- 15465711
TI  - Winter fawn survival in black-tailed deer populations affected by hair loss
      syndrome.
AB  - Overwinter fawn mortality associated with hair loss syndrome (HLS) is anecdotally
      thought to be important in declines of Columbian black-tailed deer (Odocoileus
      hemionus columbianus) populations in Washington and Oregon (USA). We determined
      prevalence of HLS in black-tailed deer, September and April fawn:doe ratios, and
      minimum overwinter survival rates of fawns for selected game management units
      (GMUs) in western Washington from 1999 to 2001. Prevalence of HLS ranged from 6%
      to 74% in fawns and 4% to 33% in does. Minimum fawn survival ranged from 0.56 to
      0.83 and was unrelated to prevalence of HLS in either does (r=0.005, P=0.991) or
      fawns (r=-0.215, P=0.608). The prevalence of HLS in either does or fawns was also
      unrelated to either fall fawn:doe ratios (HLS does: r=-0.132, P=0.779; HLS fawns:
      r=0.130, P=0.760) or spring fawn:doe ratios (HLS does: r=-0.173, P=0.711; HLS
      fawns: r=-0.020, P=0.963). However, the prevalence of HLS in does and fawns was
      strongly related (r=0.942, P=0.002), and GMUs with high prevalence of HLS had
      lower deer population densities (fawns: r=-0.752, P=0.031; does: r=-0.813,
      P=0.026). Increased overwinter mortality of fawns because of HLS was not
      supported by our data. Decreased production of fawns, increased summer mortality
      of fawns, or both were seen in six of eight study GMU-year combinations. Observed
      rates of productivity and minimum fawn survival were inadequate to maintain
      population size in five of eight study GMU-year combinations, assuming an annual
      doe survival rate of 0.75. The influence of deer condition and population health
      on adult survival, fawn production, preweaning fawn survival, parasitism, and
      prevalence of HLS in both fawns and adults need to be clarified to identify what
      factors are limiting black-tailed deer productivity.

PMID- 15465712
TI  - Prevalence of Soboliphyme baturini in marten (Martes americana) populations from
      three regions of Alaska, 1990-1998.
AB  - Marten (Martes americana) carcasses were collected from trappers in three regions
      of Alaska. Stomachs were examined for the nematode parasite Soboliphyme baturini.
      Both prevalence and intensity of infection exhibited an increase from north to
      south. Prevalence was higher in adults (compared with juveniles) from the two
      mainland study areas. Prevalences in these two age classes were similar for the
      southeastern region. There were no sex-specific differences in prevalence. No
      pathologic changes were observed in the gastrointestinal tract. Impact of the
      parasite on either individual animals or populations was not detected.

PMID- 15465713
TI  - Population effects of sarcoptic mange in Barbary sheep (Ammotragus lervia) from
      Sierra Espuna Regional Park, Spain.
AB  - The nonindigenous Barbary sheep population (Ammotragus lervia) of the Sierra
      Espuna Regional Park (Murcia, Spain) suffered an outbreak of sarcoptic mange
      between 1991 and 1995, which contributed to a population decrease of 86%. This
      study presents the results of two population surveys conducted in 1994 and 1999
      based on the fixed point and itineraries method (FPI) and the excrement count
      (EC) method, as well as data from demographic estimates and clinical observations
      conducted by the Regional Administration of Murcia. Results of surveillance for
      mange are given between 1992 and 1995, because no animals were observed with
      sarcoptic mange in 1999. Prevalence of mange peaked in 1994 and then declined.
      During the regression phase of the epidemic, there was a higher infection rate in
      males (21.9%) than in females (16.6%) or young animals (5.1%). Males over 5 yr
      old were the worst affected age group, followed by subadults of both sexes. Few
      animals had generalized lesions of mange (7%), and most individuals (72%) had
      lesions of moderate severity. The most common locations of lesions were the neck,
      head, and back. The density of Barbary sheep in the Sierra Espuna Regional Park
      increased from introduction in 1972 until it peaked at 13 animals/km(2) in 1991,
      the year when the first case of sarcoptic mange was detected. After 2 yr of the
      mange epidemic, the average estimated density was 1.7 animals/km(2) in 1994,
      which increased to 5.0 animals/km(2) in 1999. The average group size also
      increased from 7.9 to 19.2 animals/group between 1994 and 1999. The sex ratio,
      expressed as the proportion of females in the total population observed,
      decreased from 0.61 in 1994 to 0.49 in 1999. The reproduction rate (kids per
      females per year) was essentially stable (0.59 in 1994 to 0.65 in 1999). Between
      1994 and 1999 the population aged, with the number of young animals (<18 mo of
      age) decreasing from 45.3% to 36.6% from 1994 to 1999. In the same period, the
      proportion of males increased 21.4% to 32.6%. We believe sarcoptic mange acted as
      one of the regulating factors of population density after 1991 and that
      currently, although no sarcoptic mange lesions were observed in the 1999 survey,
      there is a demographic imbalance in sex ratio, age structure, and density.

PMID- 15465714
TI  - Immunoglobulin responses of northern elephant and Pacific harbor seals naturally
      infected with Otostrongylus circumlitus.
AB  - Immunoglobulin (Ig) binding patterns of Pacific harbor seals (PHS, Phoca vitulina
      richardsi) and northern elephant seals (NES, Mirounga angustirostris) to tissues
      of adult Otostrongylus circumlitus were examined by immunoblotting to investigate
      the role of age in the unusual response of juvenile NES to infection with O.
      circumlitus. Serum was taken from NES between March 1997 and March 2001 and from
      PHS between May 1996 and August 1999. The serum of seals infected with O.
      circumlitus contained antibodies that bound to all nematode tissues examined.
      Intensity of band staining on Western blots suggested that there were higher
      levels of antibody recognizing the excretory-secretory (ES) glands in the serum
      of NES that were 1 yr and older and in the majority of PHS compared with that in
      2- to 9-mo-old NES. All juvenile NES infected with O. circumlitus and a
      proportion of the PHS and older NES infected with O. circumlitus contained Ig
      specific to a 28 kDa protein band that was dominant in the female reproductive
      tract of the nematode. The Ig binding patterns of NES and PHS to adult
      Parafilaroides sp., larval Pseudoterranova sp., and larval and adult Anisakis sp.
      differed sufficiently from that of O. circumlitus that immunoblotting for the 28
      kDa protein could be useful for diagnosis of this parasite in juvenile NES. The
      banding patterns suggest that O. circumlitus nematodes die and disintegrate in
      PHS and NES and that NES of 1 yr and older and most PHS respond differently to
      the ES glands than 2- to 9-mo-old NES.

PMID- 15465715
TI  - Attempts to reproduce vacuolar myelinopathy in domestic swine and chickens.
AB  - Avian vacuolar myelinopathy (AVM) was first recognized as a cause of bald eagle
      (Haliaeetus leucocephalus) mortality in 1994 in Arkansas (USA) and has since
      caused over 90 bald eagle and numerous American coot (Fulica americana)
      mortalities in five southeastern states. The cause of AVM remains undetermined
      but is suspected to be a biotoxin. Naturally occurring AVM has been limited to
      wild waterbirds, raptors, and one species of shorebird, and has been reproduced
      experimentally in red-tailed hawks (Buteo jamaicensis). In this study, chickens
      and swine were evaluated for susceptibility to vacuolar myelinopathy with the
      intent of developing animal models for research and to identify specific tissues
      in affected coots that contain the causative agent. Additionally, submerged,
      aquatic vegetation, primarily hydrilla (Hydrilla verticillata), and associated
      material collected from a reservoir during an AVM outbreak was fed to chickens in
      an effort to reproduce the disease. In two separate experiments, six 4-wk-old
      leghorn chickens and ten 5-wk-old leghorn chickens were fed coot tissues. In a
      third experiment, five 3-mo-old domestic swine and one red-tailed hawk, serving
      as a positive control, were fed coot tissues. In these experiments, treatment
      animals received tissues (brain, fat, intestinal tract, kidney, liver, and/or
      muscle) from coots with AVM lesions collected at a lake during an AVM outbreak.
      Negative control chickens and one pig received tissues from coots without AVM
      lesions that had been collected at a lake where AVM has never been documented. In
      a fourth experiment, eight 3-wk-old leghorn chickens were fed aquatic vegetation
      material. Four chickens received material from the same lake from which coots
      with AVM lesions were collected for the previous experiments, and four control
      chickens were fed material from the lake where AVM has never been documented.
      Blood was collected and physical and neurologic exams were conducted on animals
      before and once per week during the trials. All animals were sacrificed and
      necropsies were performed on Day 29 of feeding, with the exception of one treated
      chicken that was sacrificed and necropsied on Day 15 of feeding. Microscopic
      lesions of vacuolar myelinopathy were present in the red-tailed hawk and five
      chickens that received a mixture of all tissues and two chickens that received
      only gastrointestinal tissues of coots with AVM lesions. Three of four treated
      chickens in the aquatic vegetation trial developed vacuolar lesions. None of four
      treatment pigs or any of the negative control animals developed vacuolar lesions.
      Chickens are susceptible to AVM and may serve as a useful animal model for future
      studies. Swine may be refractory to AVM or not affected by AVM at the same dose
      as are chickens and red-tailed hawks. The causative agent of AVM in affected
      coots is associated with the gastrointestinal tissues. Furthermore, AVM can be
      reproduced in chickens via ingestion of aquatic vegetation and associated
      materials collected from a lake during an AVM outbreak. The cause of AVM is most
      likely present in the materials associated with submerged vegetation because the
      vegetation itself (hydrilla) was the same at our AVM-positive and AVM-negative
      sites.

PMID- 15465716
TI  - Establishing a food-chain link between aquatic plant material and avian vacuolar
      myelinopathy in mallards (Anas platyrhynchos).
AB  - Avian vacuolar myelinopathy (AVM) is a neurologic disease primarily affecting
      bald eagles (Haliaeetus leucocephalus) and American coots (Fulica americana). The
      disease was first characterized in bald eagles in Arkansas in 1994 and then in
      American coots in 1996. To date, AVM has been confirmed in six additional avian
      species. Attempts to identify the etiology of AVM have been unsuccessful to date.
      The objective of this study was to evaluate dermal and oral routes of exposure of
      birds to hydrilla (Hydrilla verticillata) and associated materials to evaluate
      their ability to induce AVM. Mallards (Anas platyrhynchos) were used in all
      trials; bobwhite quail (Colinus virginianus) also were used in one fresh hydrilla
      material exposure trial. Five trials were conducted, including two fresh hydrilla
      material exposure trials, two cyanobacteria exposure trials, and a frozen
      hydrilla material exposure trial. The cyanobacteria exposure trials and frozen
      hydrilla material trial involved gavaging mallards with either Pseudanabaena
      catenata (live culture), Hapalosiphon fontinalis, or frozen hydrilla material
      with both cyanobacteria species present. With the exception of one fresh hydrilla
      exposure trial, results were negative or inconclusive. In the 2002 hydrilla
      material exposure trial, six of nine treated ducks had histologic lesions of AVM.
      This established the first cause-effect link between aquatic vegetation and AVM
      and provided evidence supporting an aquatic source for the causal agent.

PMID- 15465717
TI  - Organochlorine pesticides in chorioallantoic membranes of Morelet's crocodile
      eggs from belize.
AB  - Recent studies examined the utility of the chorioallantoic membrane (CAM) as a
      nonlethal, noninvasive indicator of environmental contaminant exposure in
      oviparous wildlife. The CAM is a highly vascularized extraembryonic membrane that
      functions as a site for respiration, nutrient transport, and waste storage during
      embryonic development. After hatching, the CAM is usually discarded with the
      eggshell and can be used for chemical residue analysis. Chorioallantoic membranes
      have been used successfully to examine contaminant exposure and predict chemical
      concentrations in multiple species of birds and reptiles. In this study, we
      examined organochlorine (OC) pesticide concentrations in CAMs from eggs of
      Morelet's crocodiles (Crocodylus moreletii) from northern Belize. Multiple OCs
      were detected in crocodile CAMs, including aldrin, dieldrin, endrin,
      dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethane,
      dichlorodiphenyldichloroethylene (DDE), heptachlor, lindane, and methoxychlor.
      Number and concentrations of OC compounds in CAMs were variable. The most
      prevalent contaminant detected was DDE, which occurred in 69% of CAMs, with
      concentrations ranging from 0.3 parts per billion (ppb) to 17.0 ppb. The OC
      burdens in crocodile CAMs confirm contamination of eggs and suggest exposure in
      embryos and maternal females. These results further support the use of CAMs as
      qualitative indicators of OC exposure in oviparous wildlife. The efficacy of this
      sampling technique in the field will depend on the logistics and cost associated
      with CAM collection and the specific life history traits of the wildlife species.

PMID- 15465718
TI  - Mercury and persistent organic pollutant concentrations in African fish eagles,
      marabou storks, and Nile tilapia in Uganda.
AB  - The purpose of this research was to evaluate persistent organic pollutant (POP)
      and mercury concentrations in tissues of African fish eagles (Haliaeetus vocifer)
      and Nile tilapia (Oreochromis niloticus) from Lake Victoria near Entebbe and Lake
      Mburo, Uganda. Marabou stork (Leptoptilos crumeniferus) nestlings from urban
      Kampala (40 km from Entebbe) also were sampled for POPs and mercury. Total
      mercury was measured in the breast feathers of eight nestling and 10 adult
      African fish eagles from Lake Mburo, 10 nestling and five adult African fish
      eagles from Lake Victoria near Entebbe, and 20 nestling marabou storks from
      Kampala from June 2002 through January 2003. Mercury concentrations in all
      samples were below levels associated with adverse effects in similar species.
      Mercury concentrations were significantly higher in eagle adults and nestlings
      from Entebbe than in adults and nestlings from Lake Mburo (P< or =0.05). No
      significant differences (P> or =0.05) were found in mercury concentrations
      between sexes or between the entire fish eagle population sampled at Entebbe and
      marabou stork nestlings sampled at nearby Kampala. Plasma samples from the same
      birds were analyzed for 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane, aldrin,
      hexachlorocyclohexane (alpha-HCH), dieldrin, endrin, heptachlor and their
      metabolites, as well as total polychlorinated biphenyls (PCBs). Nile tilapia
      whole-body cross sections collected from Lake Mburo (n=3) and Lake Victoria near
      Entebbe (n=8) also were analyzed for these POPs and mercury. No samples contained
      POPs or PCBs at the limits of detection except for 4,4'-1,1-dichloro-2,2-bis(4
      chlorophenyl)ethylene in five adult eagle plasma samples (0.0026+/-0.0015 ppm wet
      weight) and five Nile tilapia samples (0.002+/-0.001 ppm wet weight) from
      Entebbe.

PMID- 15465719
TI  - Bone assessment of free-living red squirrels (Sciurus vulgaris) from the United
      Kingdom.
AB  - Metabolic bone disease has been reported in free-living red squirrels (Sciurus
      vulgaris) in the United Kingdom but the prevalence of this disease is unknown. In
      this study the bone quality of free-living red squirrels in the UK was assessed
      by radiology and bone densitometry. The study comprised 20 red squirrels found
      dead and submitted to the Zoological Society of London (UK) between 1997 and
      1998, 10 were from the Isle of Wight (IoW), where gray squirrels (Sciurus
      carolinensis) are absent, and 10 were from Cumbria (Cu), where gray squirrels are
      present. Gray squirrels are considered potential competitors for red squirrels.
      Radiologic evaluation of humerus, femur, tibia, radius, and ilium revealed a
      slightly lower bone density and thinner cortices in red squirrels from the IoW
      when compared with those from Cu. Dual-energy X-ray absorptiometry was used to
      measure bone mineral content and density of the isolated right humerus and femur
      of 19 of the 20 red squirrels. The bone densitometry study reinforced the
      radiographic findings. The IoW specimens had lower bone mineral density values,
      although statistical significance (P<0.05) between animals from the IoW and Cu
      was only reached for the proximal epiphysis of the femur and between males from
      the IoW and males from Cu for the proximal epiphysis of the humerus. A highly
      positive correlation (r>0.94) was found when the bone mineral content and density
      between the femur and the humerus among groups and within each group were
      compared, showing a uniform level of mineralization between upper and lower
      limbs. These findings suggested generalized bone loss for the IoW red squirrels
      that may be compatible with some degree of osteopenia. Within the wide range of
      causes that lead to osteopenia, malnutrition (especially protein deficiency),
      calcium and copper deficiencies, and genetic factors remain as possible
      etiologies.

PMID- 15465720
TI  - Clinical pathology and morphometrics of African fish eagles in Uganda.
AB  - Packed cell volumes (PCVs) and plasma chemistry parameters were measured in 15
      adult and 18 nestling African fish eagles (Haliaeetus vocifer) sampled from June
      2002 through January 2003 in Uganda. Morphologic measurements were obtained from
      15 adult eagles. All eagles were examined for blood parasites and sexed by
      examination of DNA from red blood cells. Ten adults and eight nestlings were
      sampled from Lake Mburo and five adults and 10 nestlings were sampled from Lake
      Victoria near Entebbe, Uganda. Analysis of variance was conducted to assess the
      association between site, age, sex, and plasma chemistry parameters and the
      association between sex and morphologic characteristics. Plasma chemistry values
      for nestling and adult African fish eagles were similar to those reported for
      other captive and free-ranging eagle species. Packed cell volumes for nestling
      African fish eagles were markedly lower than values reported for nestlings of
      other eagle species, although the mean estimated age of nestlings sampled also
      was lower. A significant association (P < or =0.05) was found between PCV of
      nestling eagles and study site (lower at Lake Mburo) but no association was found
      between PCV and nestling body weight (P> or =0.05). An unidentified Plasmodium
      sp. was present in erythrocytes of three nestlings from Lake Mburo. No other
      blood parasites were seen. There was significant variation (P< or =0.05) in PCV,
      calcium, phosphorous, potassium, cholesterol concentrations, and creatine kinase
      activity between adults and nestlings; all were lower in adults. Aspartate
      transaminase activity was higher in adults. Like other Haliaeetus sp., body
      weight, bill depth, culmen length, footpad length, and hallux length as well as
      bill depth measurements were significantly (P < or = 0.05) greater for females
      than males. The objective of the study was to provide baseline biologic and
      physiologic information that may prove useful in the management and study of
      captive and wild populations of African fish eagles.

PMID- 15465721
TI  - Effectiveness of antagonists for tiletamine-zolazepam/xylazine immobilization in
      female white-tailed deer.
AB  - A combination of tiletamine-zolazepam/xylazine (TZ/X) is effective in the
      chemical immobilization of white-tailed deer (Odocoileus virginianus); however,
      the lengthy duration of immobilization may limit its usefulness. From October to
      November 2002, 21 captive female deer were assigned randomly to an alpha(2)
      antagonist treatment to reverse xylazine-induced sedation (seven does per group).
      All deer were given 220 mg of TZ (4.5+/-0.4 mg/kg) and 110 mg of X (2.2+/-0.2
      mg/kg) intramuscularly (IM). Antagonist treatments were either 200 mg of
      tolazoline (4.0+/-0.4 mg/kg), 11 mg of atipamezole (0.23+/-0.02 mg/kg), or 15 mg
      of yohimbine (0.30+/-0.02 mg/kg) injected, half intravenously and half
      subcutaneously, 45 min after the IM TZ/X injection. In addition, 10 other deer
      (five per group) were immobilized as before and then given tolazoline (200 mg)
      after 45 min, with either a carrier (dimethyl sulfoxide [DMSO]) or carrier (DMSO)
      plus flumazenil (5 mg) to reverse the zolazepam portion of TZ. Mean times from
      antagonist injection until a deer raised its head were different for alpha(2)
      antagonist treatments (P=0.02). Times were longer for yohimbine (62.3+/-42.7 min)
      than for either atipamezole (24.3+/-17.1 min) or tolazoline (21.3+/-14.3 min).
      Mean times from antagonist injection until standing were not different (P=0.15)
      among yohimbine (112.0+/-56.4 min), atipamezole (89.7+/-62.8 min), or tolazoline
      (52.6+/-37.2 min). A sedation score based on behavioral criteria was assigned to
      each deer every 30 min for 5 hr. On the basis of sedation scores, tolazoline
      resulted in a faster and more complete reversal of immobilization. Flumazenil
      treatment did not affect recovery.

PMID- 15465722
TI  - West Nile virus infection in the eastern loggerhead shrike (Lanius ludovicianus
      migrans): pathology, epidemiology, and immunization.
AB  - An outbreak of West Nile virus (WNV) infection occurred at a captive breeding
      facility for the endangered eastern loggerhead shrike (Lanius ludovicianus
      migrans) in August 2002. Within 10 d, five birds died; two were found dead, and
      the others died shortly after showing neurologic signs. West Nile virus was
      detected in all organs examined using immunohistochemistry, and its viral genome
      was amplified from brain and kidney samples using reverse transcription
      polymerase chain reaction. None of the remaining birds in the colony had
      antibodies against WNV, which suggests a mortality rate of 100%. After
      vaccination with a commercial equine WNV vaccine 31 of 37 (84%) of the birds had
      WNV neutralizing antibodies.

PMID- 15465723
TI  - Ectoparasites of the swift fox in northwestern Texas.
AB  - Ectoparasites were collected from chemically immobilized swift foxes (Vulpes
      velox) in the Texas Panhandle (USA). Three species of fleas (Pulex irritans,
      Dactylopsylla percernis, and Euhoplopsyllus affinis) and one species of tick
      (Ixodes sculptus) were found. Pulex irritans was the only abundant ectoparasite;
      it occurred on all 23 foxes brushed in 1999-2000 and all but one of 34 hosts
      examined in 2000-01. Otherwise, this swift fox population had a depauperate
      ectoparasite fauna; the remainder of the ectoparasites only occurred on a few (<
      or =5%) of the hosts. Because of previous taxonomic confusion between P. irritans
      and the closely related P. simulans, the zoogeographic distribution of these two
      species in many areas of western North America needs to be verified. Apparently,
      only the human flea P. irritans occurs on wild canids in the Texas Panhandle.
      However, there are previous records of P. simulans on other carnivores in western
      and central Texas. Some of these specimens were reexamined, and their
      identifications were reconfirmed. Also, the recent literature on the
      controversial taxonomic status of these two flea species is reviewed. The male
      terminal aedeagal sexual apparatus is the only means currently available to
      separate P. irritans and P. simulans.

PMID- 15465724
TI  - Occurrence of Helicobacter Infection in the gastric mucosa of free-living red
      foxes (Vulpes vulpes).
AB  - We studied gastric Helicobacter spp. in five red foxes (Vulpes vulpes). Samples
      of stomach from the cardia, corpus, pyloric antrum, and duodenum were subjected
      to histopathologic, immunohistochemical, and transmission electron microscopy
      (TEM) examination for the presence of Helicobacter and gastritis. All foxes had
      gastric Helicobacter-like organisms (GHLOs) on examination by light microscopy
      and TEM. Gastric Helicobacter-like organisms were present in all areas of the
      stomachs. Chronic mild or moderate gastric inflammation was associated with
      infection by GHLOs in one or more regions of the stomach, but there was no
      correlation between inflammation and infection. It is not clear whether the
      organisms were causing the minimal histologic lesions observed, but the gastric
      mucosa of free-living foxes appears to be commonly colonized with GHLOs. The
      frequent colonization of free-living foxes with distinct GHLOs possibly reflects
      their special characteristic in feeding and/or social behavior or the potential
      commensal nature of the bacteria in free-ranging foxes.

PMID- 15465725
TI  - Additional observations on blood parasites of birds in Costa Rica.
AB  - Birds from the Area de Conservacion Guanacaste in northwestern Costa Rica were
      surveyed for blood parasites in June 2001 and December 2001-January 2002. Of 354
      birds examined, representing 141 species of 35 families and 15 orders, 44 (12.4%)
      were infected with blood parasites. Species of Haemoproteus (4.8% prevalence),
      Plasmodium (0.6%), Leucocytozoon (0.3%), Trypanosoma (2.0%), and microfilariae
      (7.6%) were recorded. Twelve species of birds in this survey were examined for
      blood parasites for the first time. Several new host-parasite associations were
      identified.

PMID- 15465726
TI  - Intranasal administration of xylazine to reduce stress in elk captured by net
      gun.
AB  - Forty free-ranging elk (Cervus elaphus manitobensis) were captured by net gun in
      Riding Mountain National Park (Manitoba, Canada) during February 2002 and were
      administered either saline (control) or xylazine by the intranasal route, to
      evaluate the efficacy and benefit of intranasal xylazine to reduce stress. Elk
      that received xylazine had higher relaxation scores than control elk, and the
      onset of sedation occurred quickly, often <1 min. Serum concentrations of
      cortisol, creatine kinase, and gamma-glutamyltransferase were lower in elk that
      received xylazine than in control elk. At the conclusion of handling, the
      intravenous administration of yohimbine quickly abolished the sedative effect of
      xylazine, which allowed elk to be released without concern of physical injury due
      to ataxia. The intranasal administration of xylazine can be used to reduce stress
      in wild animals under situations where they are being handled while physically
      restrained.

PMID- 15465727
TI  - A comparison of Salmonella serotypes isolated from New Zealand sea lions and
      feral pigs on the Auckland Islands by pulsed-field gel electrophoresis.
AB  - The Salmonella serotypes S. Cerro and S. Newport were isolated from New Zealand
      sea lions (Phocarctos hookeri) and feral pigs on the Auckland Islands in the New
      Zealand subantarctic region. The isolates were typed by pulsed-field gel
      electrophoresis using Xba1 as the restriction enzyme. The isolates were
      indistinguishable, which suggests that Salmonella infection cycles between sea
      lions and pigs in this environment. Apart from a previous isolation from a single
      New Zealand fur seal (Arctocephalus forsteri), S. Newport has not been recorded
      in any animals from New Zealand, but it is associated with gastroenteritis in
      humans. Contamination of the marine environment by human waste is a possible
      source of infection for marine mammals and warrants further investigation.

PMID- 15465728
TI  - Peracute sodium toxicity in free-ranging black-bellied whistling duck ducklings.
AB  - From 23 to 25 July 2002, 98-103 newly hatched black-bellied whistling ducks
      (Dendrocygna autumnalis) were observed alive at an inland saline lake (La Sal
      Vieja) in Willacy County, Texas (USA). Seventy-one (71%) died after showing signs
      indicative of sodium toxicity within 5 hr of entering the water; some died within
      minutes. Six carcasses were sent to the United States Geological Survey, National
      Wildlife Health Center (Madison, Wisconsin, USA) for analysis, and brain sodium
      levels of all ducklings were above 2,000 parts per million wet weight. More black
      bellied whistling duck ducklings are likely to have been affected, but they were
      not observed after hatching.

PMID- 15465729
TI  - Comparative immobilization of wild felids in Thailand.
AB  - We immobilized individuals of four free-ranging felid species, leopard cat
      (Prionailurus bengalensis), clouded leopard (Neofelis nebulosa), Asiatic golden
      cat (Catopuma temminckii), and marbled cat (Pardofelis marmorata) with ketamine
      hydrochloride and xylazine hydrochloride (KH-XH) and with tiletamine
      hydrochloride and zolazepam hydrochloride (TH-ZH) between March 1998 and July
      2002. Mean (+/-SD) dose of KH and XH was 26.51+/-5.71 mg/kg and 1.89+/-0.43
      mg/kg, respectively (n=25), and mean dose of TH-ZH was 11.61+/-3.39 mg/kg (n=28).
      Dose was significantly correlated with induction time (P<0.001) and duration of
      anesthesia (P<0.05), but not with recovery time. There were significant
      differences between the drug combinations in time to induction (P<0.03) and time
      to anesthesia (P<0.01); recovery times were not significantly different. We
      conclude that immobilization of these felids with TH-ZH and KH-XH is effective
      and safe, but TH-ZH is preferred because of the smaller volume of drug necessary
      for sedation, faster time to induction, and absence of prolonged muscle rigidity
      during anesthesia.

PMID- 15465730
TI  - Strongyloides robustus and the northern sympatric populations of northern
      (Glaucomys sabrinus) and southern (G. volans) flying squirrels.
AB  - Within North America, northern (Glaucomys sabrinus) and southern (Glaucomys
      volans) flying squirrels occupy distinct ranges with limited overlap. Sympatry in
      northern latitudes coincides with northern hardwood vegetation from Minnesota to
      New England. Strongyloides robustus is an intestinal parasite that infects both
      species but appears to be deleterious only to northern flying squirrels. As a
      result, S. robustus could be a critical determinant of flying squirrel population
      characteristics in at least some areas of sympatry. However, cold weather could
      potentially limit the distribution of S. robustus in northern climates.
      Therefore, we assessed fecal samples from both flying squirrel species to
      determine the presence of the nematode in Wisconsin. Strongyloides robustus was
      found in 12 flying squirrel scat samples and infected 52% of southern flying
      squirrels and 11% of northern flying squirrels. Prevalence of S. robustus
      infection for northern flying squirrels was substantially lower than previously
      reported from more southern regions. This is the northernmost documentation of S.
      robustus in flying squirrels and the first documentation of S. robustus
      parasitizing flying squirrels in Wisconsin.

PMID- 15465731
TI  - Salmonella Amager, Campylobacter jejuni, and urease-positive thermophilic
      Campylobacter found in free-flying peregrine falcons (Falco peregrinus) in
      Sweden.
AB  - Rare species with small population sizes are vulnerable to perturbations such as
      disease, inbreeding, or random events. The threat arising from microbial
      pathogens could be large and other species could act as reservoirs for pathogens.
      We report finding three enteric bacterial species, Salmonella Amager,
      Campylobacter jejuni, and urease-positive thermophilic Campylobacter, in nestling
      free-flying peregrine falcons (Falco peregrinus) in Sweden in 2000. Campylobacter
      jejuni isolates exhibited marked genetic similarities to an isolate from a human,
      providing a possible association between a human-associated strain of this
      bacterium and peregrine falcons.

PMID- 15465732
TI  - Struvite penile urethrolithiasis in a pygmy sperm whale (Kogia breviceps).
AB  - Massive urolithiasis of the penile urethra was observed in an adult pygmy sperm
      whale (Kogia breviceps) stranded on Topsail Island, North Carolina, USA. Calculi
      occupied the urethra from just distal to the sigmoid flexure to the tip of the
      penis for a length of 43 cm. A urethral diverticulum was present proximal to the
      calculi. The major portion of the multinodular urolith weighed 208 g and was 16
      cm long x 3.7 cm diameter at the widest point. The urolith was composed of 100%
      struvite (magnesium ammonium phosphate) and on culture yielded Klebsiella
      oxytoca, a urease-positive bacterium occasionally associated with struvite
      urolith formation in domestic animals. Reaction to the calculi was characterized
      histologically by moderate multifocal to coalescing plasmacytic balanitis and
      penile urethritis. Role of the urethrolithiasis in the whale's stranding is
      speculative but could have involved pain or metabolic perturbations such as
      uremia or hyperammonemia.

PMID- 15465733
TI  - Clinical pathology of nestling marabou storks in Uganda.
AB  - Packed cell volumes (PCV) and plasma chemistry parameters were measured in 20
      nestling marabou storks (Leptoptilos crumeniferus) in January 2003 that were a
      part of a colony located in the center of the city of Kampala, Uganda. There were
      no significant differences (P> or =0.05) in plasma chemistry values or PCV
      between sexes with the exception of globulin and total plasma protein values,
      which were higher in females. There were significant differences (P< or =0.05) in
      blood glucose, creatine kinase, and globulin levels between birds of different
      body weight. Total plasma protein, uric acid, phosphorous, and creatine kinase
      were generally higher relative to published data on other avian species,
      including nestling white storks (Ciconia ciconia).

PMID- 15465734
TI  - Lead shot poisoning of a pacific loon in Alaska.
AB  - Lead poisoning, associated with ingestion of spent lead shot, was diagnosed in an
      adult female Pacific loon (Gavia pacifica) observed with partial paralysis on 13
      June 2002 and found dead on 16 June 2002 on Kigigak Island, Yukon Delta National
      Wildlife Refuge, western Alaska, USA. A necropsy revealed three pellets of
      ingested lead shot in the loon's gizzard and a lead liver concentration of 31 ppm
      wet weight, which was consistent with metallic lead poisoning. This is the first
      report of lead poisoning in a Pacific loon and is the only account of lead
      toxicosis associated with ingestion of lead shot in any loon species breeding in
      Alaska.

PMID- 15465735
TI  - Cardiac rhabdomyoma in a juvenile fallow deer (Dama dama).
AB  - A cardiac rhabdomyoma is described in a 6-wk-old captive fallow deer (Dama dama)
      that died suddenly without previous clinical signs. The tumor was characterized
      by multiple nodules composed of large atypical vacuolated myoblastic cells. As
      previously reported in humans and other animal species, there is compelling
      evidence that the cardiac rhabdomyoma is a congenital developmental anomaly
      rather than a true neoplasm. To our knowledge, this is the first report of a
      cardiac tumor and a rhabdomyoma in a cervid species.

PMID- 15465736
TI  - Foot infections associated with Arcanobacterium pyogenes in free-living fallow
      deer (Dama dama).
AB  - We describe foot infection associated with Arcanobacterium pyogenes in three
      adult male free-living fallow deer (Dama dama) from Sueve Regional Hunting
      Reserve (Principality of Asturias, Spain). Affected fallow deer were culled in
      November 1997 and 1998 during the hunting season. Necropsy, radiography, and
      microbiologic analysis were carried out for each animal. Unilateral swelling of
      one extremity at the coronary band was observed in all three cases. Areas of bone
      loss, severe periosteal reaction, and soft tissue swelling were seen on
      radiography. Lead fragments were observed in one fallow deer. Seven bacterial
      species were isolated, but only Arcanobacterium pyogenes was routinely found.
      Weather conditions in the area (mild temperatures and high humidity), the land
      (alternating pasture land and rock), the animal population density (both fallow
      deer and domestic herds of cows, horses, sheep, and goats, live side by side in
      the same areas), and hunting activities could be related to the frequency of
      these infections.

PMID- 15465737
TI  - The hypoglycemic effects of hesperidin and naringin are partly mediated by
      hepatic glucose-regulating enzymes in C57BL/KsJ-db/db mice.
AB  - Dietary antioxidant compounds such as bioflavonoids may offer some protection
      against the early stage of diabetes mellitus and the development of
      complications. We investigated the effect of citrus bioflavonoids on blood
      glucose level, hepatic glucose-regulating enzymes activities, hepatic glycogen
      concentration, and plasma insulin levels, and assessed the relations between
      plasma leptin and body weight, blood glucose, and plasma insulin. Male C57BL/KsJ
      db/db mice (db/db mice, 5 wk old), an animal model for type 2 diabetes, were fed
      a nonpurified diet for 2 wk and then were fed an AIN-76 control diet or the
      control diet supplemented with hesperidin (0.2 g/kg diet) or naringin (0.2 g/kg
      diet). Hesperidin and naringin supplementation significantly reduced blood
      glucose compared with the control group. Hepatic glucokinase activity and
      glycogen concentration were both significantly elevated in the hesperidin- and
      the naringin-supplemented groups compared with the control group. Naringin also
      markedly lowered the activity of hepatic glucose-6-phosphatase and
      phosphoenolpyruvate carboxykinase compared with the control group. Plasma
      insulin, C-peptide, and leptin levels in the db/db mice from the 2 bioflavonoid
      supplemented groups were significantly higher than those of the control group.
      Furthermore, plasma leptin was positively correlated with plasma insulin level (r
      = 0.578, P < 0.01) and body weight (r = 0.541, P < 0.05), and was inversely
      correlated with the blood glucose level (r = -0.46, P < 0.05). The current
      results suggest that hesperidin and naringin both play important roles in
      preventing the progression of hyperglycemia, partly by increasing hepatic
      glycolysis and glycogen concentration and/or by lowering hepatic gluconeogenesis.

PMID- 15465738
TI  - Dietary nucleotides enhance the liver redox state and protein synthesis in
      cirrhotic rats.
AB  - Cirrhosis is characterized by altered lipid and protein metabolism and an
      excessive accumulation of extracellular matrix components. The aim of this work
      was to determine the effect of dietary nucleotide intake on the intracellular
      pools of nucleic acids and nucleotides, hepatic redox state, and protein
      synthesis during cirrhosis. Rats were given 300 mg/L thioacetamide (TAA) in
      drinking water and were fed diets without (TAA-Nt) or with nucleotides (Nt)
      (TAA+Nt, 3 g each of AMP, inosine 5'-monophosphate, CMP, GMP, and UMP per kg
      diet) for 4 mo. The degree of liver histological injury was less in group TAA+Nt
      than in TAA-Nt. The intake of nucleotides significantly increased the hepatic
      concentration of total nucleotides, adenine nucleotides, and ATP+ADP+AMP.
      Interestingly, the concentration of CDP-choline, a nucleotide necessary for
      phospholipid synthesis, was significantly higher in TAA+Nt than in TAA-Nt. The
      hepatic pyruvate:lactate (P = 0.075) and acetoacetate:beta-hydrodybutyrate (P <
      0.05) ratios, indicators of cytosolic and mitochondrial redox states, were lower
      in TAA-Nt than in TAA+Nt. The total protein concentration was higher in the
      livers of TAA+Nt than in TAA-Nt. Although there were no differences in the
      expression of the albumin gene, the hepatic albumin concentration was
      significantly higher in TAA+Nt than in TAA-Nt. These data indicate that the
      reduction of liver injury in nucleotide-supplemented rats may be due to the
      increased intracellular availability of key metabolic nucleotides, the
      restoration of mitochondrial function, and the augmentation of protein synthesis.

PMID- 15465739
TI  - Epicatechin and a cocoa polyphenolic extract modulate gene expression in human
      Caco-2 cells.
AB  - We performed a functional genomic analysis to study the effect of epicatechin and
      polyphenolic cocoa extract in the human colon adenocarcinoma cell line Caco-2.
      The specific Human Hematology/Immunology cDNA arrays by Clontech, containing 406
      genes in duplicate, were used. The differentially expressed genes were classified
      according to their level of expression, calculated as the ratio of the value
      obtained after each treatment relative to control cells, with a statistical
      significance of P < 0.05 (upregulated: ratio > 1.5; downregulated: ratio < 0.6).
      Treatment with epicatechin decreased the expression of 21 genes and upregulated
      24 genes. Upon incubation with the cocoa polyphenolic extract, 24 genes were
      underexpressed and 28 were overexpressed. The changes in expression for ferritin
      heavy polypeptide 1 (FTH1), mitogen-activated protein kinase kinase 1 (MAPKK1),
      signal transducer and activator of transcription 1 (STAT1), and topoisomerase 1
      upon incubation with epicatechin, and for myeloid leukemia factor 2 (MLF2),
      CCAAT/enhancer binding protein gamma (C/EBPG), MAPKK1, ATP-binding cassette,
      subfamily c member 1 (MRP1), STAT1, topoisomerase 1, and x-ray repair
      complementing defective repair 1 (XRCC1) upon incubation with the cocoa
      polyphenolic extract were validated by RT-PCR. Changes in the messenger RNA
      levels for MAPKK1, STAT1, MRP1, and topoisomerase 1 upon incubation with either
      epicatechin or cocoa extract were further confirmed at the protein level by
      Western blotting. The changes in the expression of STAT1, MAPKK1, MRP1, and FTH1
      genes, which are involved in the cellular response to oxidative stress, are in
      agreement with the antioxidant properties of cocoa flavonoids. In addition, the
      changes in the expression of C/EBPG, topoisomerase 1, MLF2, and XRCC1 suggest
      novel mechanisms of action of flavonoids at the molecular level.

PMID- 15465740
TI  - The effect of dietary fat on LDL size is influenced by apolipoprotein E genotype
      in healthy subjects.
AB  - LDL particle size is dependent on both genetic factors and environmental factors
      such as dietary fat composition. The apolipoprotein E (apoE) genotype is a major
      genetic determinant of LDL size. Thus, the aim of this work was to study whether
      the apoE genotype interacts with the quantity and quality of dietary fat,
      modifying LDL size in young healthy subjects. Healthy subjects (n = 84; 66 apoE
      3/3, 8 apoE 4/3, 10 apoE 3/2) were subjected to 3 dietary periods, each lasting 4
      wk. The first was an SFA-enriched diet (38% fat, 20% SFA), which was followed by
      a carbohydrate (CHO)-rich diet (30% fat, < 10% SFA, 55% carbohydrate) or a
      monounsaturated fatty acid (MUFA) olive oil-rich diet (38% fat, 22% MUFA)
      following a randomized crossover design. At the end of each diet period, LDL
      particle size and plasma levels of total cholesterol, LDL cholesterol (LDL-C),
      HDL-C, apoB, apoA-I, and triacylglycerols were determined. LDL particle size was
      significantly higher (P < 0.04) in subjects with the apoE 4/3 genotype compared
      with those with apoE 3/3 and apoE 3/2 in the basal state. LDL size was smaller (P
      < 0.02) after the CHO diet than after the MUFA or SFA diets. After the CHO diet,
      a significant increase in LDL particle size (P < 0.035) was noted with respect to
      the MUFA diet in apoE 4/3 subjects, whereas a significant decrease was observed
      in the apoE 3/3 individuals (P < 0.043). In conclusion, a Mediterranean diet,
      high in MUFA-fat increases LDL particle size compared with a CHO diet, and this
      effect is dependent of apoE genotypes.

PMID- 15465741
TI  - The inhibitory effect of trans-10, cis-12 CLA on lipid synthesis in bovine
      mammary epithelial cells involves reduced proteolytic activation of the
      transcription factor SREBP-1.
AB  - The trans-10, cis-12 CLA isomer has been causally related to milk fat depression
      in dairy cows, although no molecular mechanism has been established. Sterol
      response element-binding protein (SREBP)-1 is a transcription factor synthesized
      and retained as a membrane-bound precursor in the endoplasmic reticulum and
      proteolytically cleaved to release an active fragment that migrates to the
      nucleus to stimulate lipogenic gene transcription. Certain lipid molecules (i.e.,
      PUFA) were shown to inhibit the proteolytic activation of SREBP-1 in rodent liver
      models, although there has been no previous demonstration of its presence in
      bovine tissues or in mammary tissue of any species. We used a bovine mammary cell
      line (MAC-T) to assess the involvement of SREBP-1 in the regulation of lipid
      synthesis in bovine mammary cells by trans-10, cis-12 CLA. Treatment with 75
      micromol/L trans-10, cis-12 CLA for 48 h resulted in an approximately 50%
      reduction of (14)C-acetate incorporation into total lipid and corresponding
      reductions in mRNA abundance for acetyl CoA carboxylase, fatty acid synthase, and
      stearoyl CoA desaturase, whereas cis-9, trans-11 CLA had no effect on these
      genes. There was no reduction in SREBP-1 mRNA or precursor protein, but the
      abundance of the activated nuclear fragment of the protein was significantly
      reduced by treatment with 75 micromol/L trans-10, cis-12 CLA. These results
      indicate that trans-10, cis-12 CLA reduces lipid synthesis in the bovine mammary
      gland through inhibition of the proteolytic activation of SREBP-1 and subsequent
      reduction in transcriptional activation of lipogenic genes.

PMID- 15465742
TI  - Caffeine ingestion before an oral glucose tolerance test impairs blood glucose
      management in men with type 2 diabetes.
AB  - Caffeine ingestion negatively affects insulin sensitivity during an oral glucose
      tolerance test (OGTT) in lean and obese men, but this has not been studied in
      individuals with type 2 diabetes. We examined the effects of caffeine ingestion
      on insulin and glucose homeostasis in obese men with type 2 diabetes. Men (n =
      12) with type 2 diabetes (age = 49 +/- 2 y, BMI = 32 +/- 1 kg/m(2)) underwent 2
      trials, 1 wk apart, in a randomized, double-blind design. Each trial was
      conducted after withdrawal from caffeine, alcohol, exercise, and oral
      hypoglycemic agents for 48 h and an overnight fast. Subjects randomly ingested
      caffeine (5 mg/kg body weight) or placebo capsules and 1 h later began a 3 h 75 g
      OGTT. Caffeine increased (P < 0.05) serum insulin, proinsulin, and C-peptide
      concentrations during the OGTT relative to placebo. Insulin area under the curve
      was 25% greater (P < 0.05) after caffeine than after placebo ingestion. Despite
      this, blood glucose concentration was also increased (P < 0.01) in the caffeine
      trial. After caffeine ingestion, blood glucose remained elevated (P < 0.01) at 3
      h postglucose load (8.9 +/- 0.7 mmol/L) compared with baseline (6.7 +/- 0.4
      mmol/L). The insulin sensitivity index was lower (14%, P = 0.02) after caffeine
      than after placebo ingestion. Overall, despite elevated and prolonged proinsulin,
      C-peptide, and insulin responses after caffeine ingestion, blood glucose was also
      increased, suggesting an acute caffeine-induced impairment in blood glucose
      management in men with type 2 diabetes.

PMID- 15465743
TI  - The apparent absorptions of isoflavone glucosides and aglucons are similar in
      women and are increased by rapid gut transit time and low fecal isoflavone
      degradation.
AB  - We hypothesized that there would be no difference in apparent absorption, as
      assessed by urinary excretion, between isoflavone sources rich in glucosides or
      aglucons and that subjects with rapid gut transit time (GTT) and low fecal
      isoflavone degradation phenotype would absorb more isoflavones. Women (n = 13)
      with a fecal daidzein degradation rate constant, D(k) > 0.30 h(-1) (high
      degraders) and GTT of 106 +/- 11 h and women (n = 12) with D(k) < 0.20 h(-1) (low
      degraders) and GTT of 71 +/- 12 h were randomly assigned to 3 treatments: soygerm
      (1.1 micromol/kg body weight, n = 5 high degraders, 4 low degraders), fermented
      soygerm (3.3 micromol/kg, n = 4 high and 4 low degraders) or Novasoy isoflavone
      extract (1.5 micromol/kg, n = 4 high and 4 low degraders) for 7 d. By HPLC
      analysis, 24-h urinary excretion of soygerm was greater than Novasoy (51 +/- 6
      vs. 26 +/- 6% of ingested dose, P < 0.05). Women of the low daidzein degradation
      phenotype had greater urinary isoflavone excretion than did women of the high
      daidzein degradation phenotype (51.6 +/- 4.8 vs. 33.8 +/- 4.7%, P < 0.05, mean of
      d1 and 7). The plasma total isoflavone level (estimated as a percentage of the
      ingested amount, mean of d 1 and 7) differed between women who consumed fermented
      soygerm and soygerm 3 h after feeding (1.8 +/- 0.3 vs. 0.5 +/- 0.3%, P < 0.05).
      Urinary excretions of aglucons and glucosides did not differ. The study confirmed
      that rapid GTT and low fecal isoflavone degradation rate increased the apparent
      absorption of isoflavones.

PMID- 15465744
TI  - Phenylalanine kinetics differ between formula-fed and human milk-fed preterm
      infants.
AB  - Infants fed casein-dominant formulas have higher plasma phenylalanine and
      tyrosine concentrations than those fed mother's milk. Conversely, elevated plasma
      threonine concentrations are observed in infants fed whey-dominant formulas. We
      recently showed that formula-fed preterm infants have a lower capacity to degrade
      threonine than do preterm infants fed mother's milk. We hypothesized that these
      same infants (n = 18) would differ in their catabolism of phenylalanine in
      response to phenylalanine loads provided by formulas with increasing casein
      content of formulas (whey:casein 60:40, 40:60, and 20:80) compared with preterm
      infants fed mother's milk. Plasma phenylalanine concentrations significantly rose
      (49, 46, 79 micromol . L(-1) for whey:casein 60:40, 40:60, and 20:80,
      respectively, pooled SD 8, P < 0.05); and plasma phenylalanine concentrations in
      infants fed mother's milk were low (40 +/- 4 micromol . L(-1)). Using [1
      (13)C]phenylalanine tracer and (13)CO(2) production in breath we found that
      although there was a significant positive relation between phenylalanine
      oxidation and phenylalanine intake in formula-fed infants (r(2) = 0.43, P =
      0.03), these infants were not able to increase their oxidation of phenylalanine
      enough to prevent a significant rise in plasma phenylalanine when fed the 20:80
      formula. Compared to infants fed mother's milk, formula-fed infants had
      significantly lower phenylalanine oxidation (39.1 vs. 30.7% of phenylalanine
      intake, respectively, P < 0.05). We conclude that one of the mechanisms for the
      differences in plasma amino acid concentration between formula-fed and mother's
      milk-fed preterm infants may be in vivo down-regulated catabolism of 2 important
      essential amino acids (phenylalanine in addition to threonine) in formula-fed
      preterm infants.

PMID- 15465745
TI  - The more food young adults are served, the more they overeat.
AB  - Young and Nestle suggested that the increase in the portion size of food products
      evident in the United States during the past 20 years may be responsible for the
      epidemic of overweight and obesity. They based their conclusion on statistical
      correlations. The purpose of the present study was to provide experimental
      evidence to support their proposal. Cornell undergraduate students were given
      access to a buffet lunch on Monday, Wednesday, and Friday and were told this was
      a test of flavor enhancers. They were instructed to eat as much or as little as
      they wanted. On the same days of the following week, the subjects were divided
      into 3 groups. Each group was served either 100%, 125%, or 150% of the amount of
      food they had consumed the previous week. When larger amounts were served,
      significantly greater amounts of food were consumed. Each of the 4 foods that
      comprised the meal (soup, pasta, breadsticks, ice cream) increased significantly
      in proportion to the portion size. The data clearly support the hypothesis
      proposed by Young and Nestle and support the powerful role that environment plays
      in determining energy intake and potential increases in body weight.

PMID- 15465746
TI  - Postprandial lipoprotein(a) is affected differently by specific individual
      dietary fatty acids in healthy young men.
AB  - Lipoprotein(a) [Lp(a)] is considered a risk factor for coronary heart disease.
      Our aim was to investigate the effect of individual fatty acids on postprandial
      plasma Lp(a) and its association with lipemia and tissue plasminogen activator (t
      PA). Five test fats dominated by (approximately 43% g/kg) stearic (S), palmitic
      (P), oleic, C18:1 trans (T), or linoleic acid were produced by
      interesterification. Sixteen young healthy men were served the individual test
      fats incorporated into meals (1g fat/kg body wt) after a 12-h fast in random
      order on different days, separated by 3-wk washout periods. Blood samples were
      drawn before and 2, 4, 6, and 8 h after eating. There was a pronounced increase
      in Lp(a) concentrations after intake of the test meals, and the test fats
      resulted in a difference in Lp(a) response (P < 0.001; diet x time interaction).
      However, T fat did not change Lp(a) during the time course studied. T fat
      resulted in less area under the plasma Lp(a) concentration curve compared to S
      and P fat (P </= 0.003). Test fat with saturated fatty acids resulted in the
      highest Lp(a) and lowest plasma triacylglycerol (TAG) response, with the reversed
      situation for T fat. There was no association between Lp(a) and t-PA. In
      conclusion, intake of meals high in individual dietary fatty acids increased
      postprandial plasma Lp(a) differently. There seems to be a complex regulatory
      role of plasma TAG on nonfasting plasma Lp(a) concentrations.

PMID- 15465747
TI  - Selenium status is associated with accelerated HIV disease progression among HIV
      1-infected pregnant women in Tanzania.
AB  - Selenium deficiency has been implicated in accelerated disease progression and
      poorer survival among populations infected with HIV in developed countries, yet
      these associations remain unexamined in developing countries. Among 949 HIV-1
      infected Tanzanian women who were pregnant, we prospectively examined the
      association between plasma selenium levels and survival and CD4 counts over time.
      Over the 5.7-y median follow-up time, 306 of 949 women died. In a Cox
      multivariate model, lower plasma selenium levels were significantly associated
      with an increased risk of mortality (P-value, test for trend = 0.01). Each 0.1
      micromol/L increase in plasma selenium levels was related to a 5% (95% CI = 0%
      9%) decreased risk of mortality. Plasma selenium levels were not associated with
      time to progression to CD4 cell count < 200 cells/mm(3) but were weakly and
      positively related to CD4 cell count in the first years of follow up. Selenium
      status may be important for clinical outcomes related to HIV disease in sub
      Saharan Africa.

PMID- 15465748
TI  - Dietary factors are not associated with high levels of obesity in New Zealand
      Pacific preschool children.
AB  - Pacific children living in New Zealand (NZ) are prone to excessive weight gain.
      In this study, we assessed the anthropometric status of 2- to 5-y-old Pacific
      children (n = 60) in relation to their macronutrient intakes. Measurements of
      height (n = 56), weight (n = 60), midarm circumference, and triceps skinfold
      thickness (n = 58), and 2-d weighed food records (n = 60) and demographic data
      were collected. Z-score results (mean +/- SD) showed that these children were
      tall (0.61 +/- 1.1) and heavy (1.67 +/- 1.1) for their age, and had high arm
      muscle-area-for-height (geometric mean, 2.05). Over 64 and 45% of children were
      classified as overweight (including obesity) and obese, respectively. The
      percentage of energy contributed by fat in their diets met recommendations. In
      contrast, the percentage of energy contributed by sugar was high. The
      macronutrient intakes of children classified as obese (n = 32) compared with non
      obese (n = 24) did not differ; however, their adjusted energy intakes were higher
      [5.79 (1.4) vs. 4.97 (1.4) MJ/d; P = 0.01]. Overweight and obesity were very
      common among very young NZ Pacific children, although the dietary etiology was
      not elucidated. These results emphasize the urgent need for obesity prevention
      for NZ Pacific children that begins early in life to avoid a future public health
      crisis.

PMID- 15465749
TI  - Food security of older children can be assessed using a standardized survey
      instrument.
AB  - Cognitive interviewing methods were used to adapt questions from the U.S. Food
      Security Survey Module for administration to children. Individual concurrent
      probing techniques using standardized probes were utilized to assess
      understanding of the items with 20 African American children (10 males, 10
      females, aged 11-13 y). Item wording and response sets were revised, and small
      groups of boys (n = 5) and girls (n = 14) aged 12-15 y were asked to complete the
      9-item survey. Retrospective probing techniques were then used to assess
      comprehension of items and response sets. Nine items were then piloted in a
      middle school using a self-administered format. Three hundred forty-five surveys
      were returned. The majority of the students were between 12 and 15 y (n = 215).
      Scaling analysis of the 345 completed surveys using statistical methods based on
      the Rasch measurement model indicated that the module measured a single
      underlying phenomenon (food insecurity) with sufficient reliability to be a
      useful tool. The measurable range of food insecurity was about 6 times the
      estimated measurement error, indicating that the scale could identify 3
      categories of food security with reasonable reliability. A survey instrument that
      reliably measures food security status of individual children can provide
      researchers with an important tool to assess more accurately the individual-level
      effects of food security on nutritional status and mental and physical health
      among this population.

PMID- 15465750
TI  - The night vision threshold test is a better predictor of low serum vitamin A
      concentration than self-reported night blindness in pregnant urban Nepalese
      women.
AB  - This study was conducted to validate the night vision threshold test (NVTT) as an
      indicator of night blindness. A total of 1401 pregnant women from the National
      Maternity Hospital participated in this study. Women were queried about night
      blindness and took the NVTT using standardized procedures after 10 min of dark
      adaptation. Sixteen percent failed the NVTT, but only 6.4% reported having night
      blindness. Blood samples from women who failed the NVTT (cases) and matched
      controls indicated the serum vitamin A (SVA) concentration was lower (P < 0.05)
      in cases (1.19 +/- 0.03 micromol/L) than in controls (1.29 +/- 0.03 micromol/L).
      The SVA concentrations did not differ between women who reported and did not
      report night blindness. The SVA concentration was correlated (r = 0.22, P <
      0.001) with the NVTT scores. Twenty-five percent of women with an SVA < 0.35
      micromol/L reported night blindness while 100% failed the NVTT. Nineteen percent
      of women with an SVA < 0.70 micromol/L reported night blindness while 73% failed
      the NVTT. A receiver operating characteristics analysis indicated that the NVTT
      had greater sensitivity (0.73 vs. 0.19) and less specificity (0.51 vs. 0.87)
      compared with reported night blindness for women with SVA < 0.70 micromol/L and
      greater sensitivity (100.0 vs. 0.73) and similar specificity (0.51 vs. 0.50) for
      women with SVA < 0.35 micromol/L. The NVTT identified women with low SVA and self
      reported night blindness was misleading. We provide a preliminary algorithm to
      predict the population of women with low SVA concentrations.

PMID- 15465751
TI  - Dietary diversity is associated with child nutritional status: evidence from 11
      demographic and health surveys.
AB  - Simple indicators reflecting diet quality for young children are needed both for
      programs and in some research contexts. Measures of dietary diversity are
      relatively simple and were shown to be associated with nutrient adequacy and
      nutritional status. However, dietary diversity also tends to increase with income
      and wealth; thus, the association between dietary diversity and child nutrition
      may be confounded by socioeconomic factors. We used data from 11 recent
      Demographic and Health Surveys (DHS) to examine the association between dietary
      diversity and height-for-age Z-scores (HAZ) for children 6-23 mo old, while
      controlling for household wealth/welfare and several other potentially
      confounding factors. Bivariate associations between dietary diversity and HAZ
      were observed in 9 of the 11 countries. Dietary diversity remained significant as
      a main effect in 7 countries in multivariate models, and interacted significantly
      with other factors (e.g., child age, breast-feeding status, urban/rural location)
      in 3 of the 4 remaining countries. Thus, dietary diversity was significantly
      associated with HAZ, either as a main effect or in an interaction, in all but one
      of the countries analyzed. These findings suggest that there is an association
      between child dietary diversity and nutritional status that is independent of
      socioeconomic factors, and that dietary diversity may indeed reflect diet
      quality. Before dietary diversity can be recommended for widespread use as an
      indicator of diet quality, additional research is required to confirm and clarify
      relations between various dietary diversity indicators and nutrient intake,
      adequacy, and density, for children with differing dietary patterns.

PMID- 15465752
TI  - Preconception hemoglobin and ferritin concentrations are associated with
      pregnancy outcome in a prospective cohort of Chinese women.
AB  - Prenatal anemia and iron deficiency are associated with adverse birth outcomes,
      but no previous studies have examined the relation between preconception anemia,
      iron deficiency, and pregnancy outcome in healthy women. We measured hemoglobin
      (Hb), ferritin, transferrin receptor (TfR), and vitamins B-6, B-12, and folate
      concentrations before pregnancy in 405 Chinese women (median time from sample
      collection to gestation end = 316 d). Both mild (95 </= Hb < 120 g/L) and
      moderate (Hb < 95 g/L) anemia were significantly associated with lower
      birthweight (139 and 192 g, respectively); iron-deficiency anemia alone (Hb < 120
      g, ferritin < 12 microg/L, no B-vitamin deficiency) was associated with a 242-g
      decrease in birthweight. Both low (<12 microg/L) and high (>/=60 microg/L)
      ferritin were also significantly associated with lower birthweight (106 and 123
      g, respectively). The risks of low birthweight (LBW) and fetal growth restriction
      (FGR) were significantly greater among women with moderate anemia compared with
      nonanemic controls [odds ratio (OR): 6.5; 95% CI: 1.6, 26.7; P = 0.009 and OR:
      4.6; 95% CI: 1.5, 13.5; P = 0.006, respectively]. TfR and low ferritin were not
      associated with adverse birth outcome, but elevated ferritin, which could be a
      marker of inflammation, was associated with increased risk of LBW (OR: 2.2; 95%
      CI: 0.9, 5.7; P = 0.09) and FGR (OR: 2.7; 95% CI: 1.3, 5.6; P = 0.008).
      Preconception anemia, particularly iron-deficiency anemia, was associated with
      reduced infant growth and increased risk of adverse pregnancy outcome in Chinese
      women.

PMID- 15465753
TI  - Multimicronutrient interventions but not vitamin a or iron interventions alone
      improve child growth: results of 3 meta-analyses.
AB  - Meta-analyses of randomized controlled intervention trials were conducted to
      assess the effects of vitamin A, iron, and multimicronutrient interventions on
      the growth of children < 18 y old. A PubMed database search and other methods
      identified 14 vitamin A, 21 iron, and 5 multimicronutrient intervention studies
      that met the design criteria. Weighted mean effect sizes and CI were calculated
      using a random effects model for changes in height and weight. Tests for
      homogeneity and stratified analyses by predefined characteristics were conducted.
      Vitamin A interventions had no significant effect on growth; effect sizes were
      0.08 (95% CI: -0.20, 0.36) for height and -0.01 (95% CI: -0.24, 0.22) for weight.
      Iron interventions also had no significant effect on child growth. Overall effect
      sizes were 0.09 (95% CI: -0.07, 0.24) for height and 0.13 (95% CI: -0.05, 0.30)
      for weight. The results were similar across categories of age, duration of
      intervention, mode and dosage of intervention, and baseline anthropometric
      status. Iron interventions did result in a significant increase in hemoglobin
      (Hb) concentrations with an effect size of 1.49 (95% CI: 0.46, 2.51).
      Multimicronutrient interventions had a positive effect on child growth; the
      effect sizes were 0.28 (95% CI: 0.16, 0.41) for height and 0.28 (95% CI: -0.07,
      0.63) for weight. Interventions limited to only vitamin A or iron did not improve
      child growth. Multimicronutrient interventions, on the other hand, improved
      linear and possibly ponderal growth in children.

PMID- 15465754
TI  - Pelargonidin is absorbed and metabolized differently than cyanidin after
      marionberry consumption in pigs.
AB  - Weaning pigs (7.9 +/- 1.7 kg) were fed a freeze-dried powder of marionberry (MB)
      by stomach tube to study the absorption and metabolism of anthocyanins. Four
      major anthocyanins (ACNs) were found in MB: cyanidin-3-glucoside (Cy-3-glc, 78%),
      cyanidin-3-rutinoside (Cy-3-rutin, 20%), pelargonidin-3-glucoside (Pg-3-glc,
      0.4%), and 1 unknown acylated cyanidin-based ACN (UACy, 1.5%). In the urine, the
      4 original ACNs and 11 metabolites were identified and quantified. The main
      metabolites were glucuronidated and/or methylated forms of the original
      anthocyanins. Total recovery of the 4 original ACNs plus their related
      metabolites was 0.087 +/- 0.034% for Cy-3-glc, 0.084 +/- 0.026% for Cy-3-rutin,
      0.583 +/- 0.229% for Pg-3-glc and 0.036 +/- 0.011% for UACy (mean +/- SD, n = 3),
      respectively. For the individual ACNs, the amount of metabolites recovered from
      Cy-3-rutin was lower than that of the original intact Cy-3-rutin, whereas the
      amounts of metabolites from Cy-3-glc and Pg-3-glc in the urine were much higher
      than their original forms. In pig plasma, the 2 original ACNs, Cy-3-glc and Cy-3
      rutin, and a trace of 1 metabolite (cyanidin monoglucuronide) were detected. The
      plasma concentration:dose ratio of Cy-3-rutin was higher than that of Cy-3-glc.
      Different aglycones and/or sugar moieties may influence the absorption and
      metabolism of ACNs. Cy-3-glc and Cy-3-rutin had similar apparent excretion rates
      relative to dose, whereas Pg-3-glc had a much higher total urinary excretion than
      cyanidin-based anthocyanins. Most of Cy-3-glc and Pg-3-glc were excreted in the
      form of metabolites, whereas most of the Cy-3-rutin was excreted in its original
      unmetabolized form. Urinary recovery of the acylated anthocyanin was lower than
      that of nonacylated anthocyanins.

PMID- 15465755
TI  - Milk sphingomyelin is more effective than egg sphingomyelin in inhibiting
      intestinal absorption of cholesterol and fat in rats.
AB  - We reported previously that egg sphingomyelin (SM) inhibits the intestinal
      absorption of cholesterol and fat in rats. This study was conducted to compare
      the relative efficiencies of milk and egg SM in inhibiting intestinal absorption
      of cholesterol and other lipids. Adult male rats with lymph cannulae were infused
      at 3.0 mL/h for 8 h via a duodenal catheter with a lipid emulsion (451.7 micromol
      triolein, 20.7 micromol cholesterol, 33.3 kBq (14)C-cholesterol, 3.1 micromol
      alpha-tocopherol, and 396.0 micromol sodium taurocholate in 24 mL PBS, pH, 6.5),
      without SM (controls), or with 80.0 micromol egg SM or milk SM. The lymphatic
      absorptions of (14)C-cholesterol were significantly lower in rats infused with
      milk SM (19.5 +/- 1.4% dose) and egg SM (24.4 +/- 1.9% dose) than in those
      infused with no SM (37.6 +/- 1.8% dose). In addition, the lymphatic outputs of
      fatty acids and phospholipid were significantly lowered by milk and egg SM.
      Similarly, the absorption of alpha-tocopherol also was decreased by milk SM (13.6
      +/- 1.7% dose) and egg SM (18.3 +/- 2.4% dose) compared with controls (27.0 +/-
      1.8% dose). Total lymphatic SM output was not affected by egg SM, but markedly
      decreased by milk SM, relative to controls. The results indicate that both milk
      and egg SM markedly inhibit the absorption of cholesterol, fat, and other lipids.
      However, milk SM is a more potent inhibitor than egg SM. The strong inhibitory
      effect of milk SM may be associated with the higher degree of saturation and
      longer chain length of its fatty acyl groups, which may slow the rate of luminal
      lipolysis, micellar solubilization, and transfer of micellar lipids to the
      enterocyte.

PMID- 15465756
TI  - Reduced and high molecular weight barley beta-glucans decrease plasma total and
      non-HDL-cholesterol in hypercholesterolemic Syrian golden hamsters.
AB  - Consumption of concentrated barley beta-glucan lowers plasma cholesterol because
      of its soluble dietary fiber nature. The role of molecular weight (MW) in
      lowering serum cholesterol is not well established. Prior studies showed that
      enzymatic degradation of beta-glucan eliminates the cholesterol-lowering
      activity; however, these studies did not evaluate the MW of the beta-glucan. The
      current study was conducted to evaluate whether barley beta-glucan concentrates,
      partially hydrolyzed to reduce MW, possess cholesterol-lowering and
      antiatherogenic activities. The reduced MW fraction was compared with a high MW
      beta-glucan concentrate from the same barley flour. Concentrated beta-glucan
      preparations were evaluated in Syrian Golden F(1)B hamsters fed a
      hypercholesterolemic diet (HCD) with cholesterol, hydrogenated coconut oil, and
      cellulose. After 2 wk, hamsters were fed HCD or diets that contained high or
      reduced MW beta-glucan at a concentration of 8 g/100 g at the expense of
      cellulose. Decreases in plasma total cholesterol (TC) and non-HDL-cholesterol
      (non-HDL-C) concentrations occurred in the hamsters fed reduced MW and high MW
      beta-glucan diets. Plasma HDL-C concentrations did not differ. HCD-fed hamsters
      had higher plasma triglyceride concentrations. Liver TC, free cholesterol, and
      cholesterol ester concentrations did not differ. Aortic cholesterol ester
      concentrations were lower in the reduced MW beta-glucan-fed hamsters. Consumption
      of either high or reduced MW beta-glucan increased concentrations of fecal total
      neutral sterols and coprostanol, a cholesterol derivative. Fecal excretion of
      cholesterol was greater than in HCD-fed hamsters only in those fed the reduced MW
      beta-glucan. Study results demonstrate that the cholesterol-lowering activity of
      barley beta-glucan may occur at both lower and higher MW.

PMID- 15465757
TI  - Equol, a metabolite of daidzein, inhibits bone loss in ovariectomized mice.
AB  - Soybean isoflavones have structures similar to that of estrogen and have received
      attention as alternatives to hormone replacement therapy for the prevention of
      postmenopausal osteoporosis. Daidzein, a major isoflavone found in soybean, is
      metabolized to equol by gut microflora, and the metabolite exhibits a stronger
      estrogenic activity than daidzein. However, there is no direct evidence that
      equol affects bone metabolism. In this study, we examined the effect of equol on
      the inhibition of bone loss in ovariectomized (OVX) mice. Female mice (8 wk old)
      were assigned to 5 groups as follows: sham-operated (sham), OVX, OVX + 0.1 mg/d
      equol administration (0.1 Eq), OVX + 0.5 mg/d equol administration (0.5 Eq), and
      OVX + 0.03 microg/d 17beta-estradiol administration (E(2)). Equol and E(2) were
      administered s.c., using a mini-osmotic pump. At 4 wk after the intervention,
      uterine weight was less in the OVX mice than in sham-operated mice (P < 0.05).
      The weight was maintained in the E(2) group. In contrast, administration of equol
      at doses used in this study did not affect uterine atrophy in OVX mice. Bone
      mineral density (BMD) for the whole body in the OVX group measured by dual-energy
      X-ray absorptiometry was lower than that in the sham group, whereas
      administration of 0.5 mg/d Eq as well as E(2) maintained the BMD. The BMD of the
      femur and lumbar spine in the OVX group was also lower than those in the sham
      group, and treatment with 0.5 mg/d Eq maintained it. Notably, the BMD of the
      proximal femur in the 0.5 Eq group was the same as that of the sham group. E(2)
      inhibited bone loss from all regions induced by OVX. These results suggest that
      equol, a major metabolite of daidzein, inhibits bone loss apparently without
      estrogenic activity in the reproductive organs of OVX mice.

PMID- 15465758
TI  - Estrogen controls branched-chain amino acid catabolism in female rats.
AB  - A diurnal rhythm occurs in the activity state of branched-chain alpha-keto acid
      dehydrogenase complex (BCKDC) in female but not male rats. We attempted to
      determine the role played by ovarian hormones in this difference in enzyme
      regulation. A series of experiments examined the effects of the 4-d estrous
      cycle, ovariectomy, and replacement of female sex steroids on the catabolism of
      BCAAs. A proestrous decrease in the activity state of the complex corresponded to
      an increase in the plasma 17beta-estradiol level. Withdrawal of gonadal steroids
      by ovariectomy resulted in an increase in the activity state of BCKDC and a
      decrease in the activity of the branched-chain alpha-keto acid dehydrogenase
      kinase (BDK). However, 17beta-estradiol reversed these effects, resulting in an
      increase in the BDK activity, thereby decreasing the activity of the complex.
      Progesterone administration was ineffective. The changes in the percentage of
      active BCKDC caused by 17beta-estradiol withdrawal and replacement resulted from
      changes in the amount of BDK protein associated with the complex and therefore
      its activity. Thus, the marked diurnal variation in the activity state of BCKDC
      exhibited by female rats involves estrogenic control of BDK activity. We
      hypothesize that the 17beta-estradiol-controlled feeding pattern produces these
      variations in BCKDC activity. This may function in female rats to conserve
      essential amino acids for protein synthesis.

PMID- 15465759
TI  - Alpha-eleostearic acid (9Z11E13E-18:3) is quickly converted to conjugated
      linoleic acid (9Z11E-18:2) in rats.
AB  - We previously showed that alpha-eleostearic acid (alpha-ESA; 9Z11E13E-18:3) is
      converted to conjugated linoleic acid (CLA; 9,11-18:2) in the liver and plasma of
      rats that were given diets including 1% alpha-ESA for 4 wk. In this study, we
      investigated this phenomenon in detail. First, the chemical structure of CLA
      produced by alpha-ESA administration was determined. After alpha-ESA was orally
      administered to rats, CLA in rat liver was isolated by HPLC. The positional and
      geometric isomerism was determined using GC-EI/MS and (13)C-NMR, respectively,
      and the CLA generated in rats after alpha-ESA feeding was confirmed to be 9Z11E
      CLA. Next, the concentrations of alpha-ESA and CLA were determined 0, 3, 6, and
      24 h after oral administration of alpha-ESA to rats. Moreover, we also
      investigated whether enteric bacteria are involved in the conversion of alpha-ESA
      to CLA using germ-free rats. alpha-ESA was orally administered to germ-free and
      normal rats and alpha-ESA and CLA were detected in the organs of both groups. In
      addition, to confirm that this reaction was enzyme-mediated, alpha-ESA was
      reacted with tissue homogenates (liver, kidney, and small intestine mucous) and
      coenzymes (NADH, NAD(+), NADPH, and NADP(+)), and the enzyme activities were
      estimated from the amount of CLA produced. CLA was detected when alpha-ESA was
      reacted with liver, kidney, and small intestine mucous homogenates and a coenzyme
      (NADPH). These results indicated that alpha-ESA is converted to 9Z11E-CLA in rats
      by a Delta13-saturation reaction carried out by an NADPH-dependent enzyme.

PMID- 15465760
TI  - Selenoprotein mRNA is expressed in blood at levels comparable to major tissues in
      rats.
AB  - Liver glutathione peroxidase-1 (GPX1) mRNA is highly regulated by Se status
      relative to other parameters, but is of limited use for determining Se
      requirements in humans. To examine the efficacy of using blood for Se status
      assessment using molecular biology markers, we used a ribonuclease protection
      assay (RPA) to study mRNA levels in whole blood relative to 16 other rat tissues.
      Significant amounts of total RNA (>50 microg) were obtained from 1 mL of whole
      blood. Total RNA from 28-d postweaning Se-adequate (0.2 microg Se/g diet) male
      rats was analyzed for GPX1, GPX4, GPX3, thioredoxin reductase-1 (TRR1), and
      selenoprotein-P (SelP). RPA detected significant mRNA expression for at least 1
      selenoprotein in all tissues except pancreas. GPX1 mRNA expression using this mix
      of RPA probes yielded the highest signal for GPX1 relative to the other
      selenoprotein signals in all tissues except testis; GPX1 expression was 4th
      highest in blood and similar to the major organs (liver, 1st; heart, 5th; kidney,
      6th). Kidney was highest for GPX3, and testes was highest for GPX4, TRR1, and
      SelP. This study is the first to report the gene expression pattern for a number
      of selenoproteins and across a comprehensive set of tissues. The mRNA levels for
      all selenoproteins in blood were comparable to levels in the major organs, and
      decreases in blood and liver GPX1 mRNA levels in Se deficiency were similar,
      supporting potential use of whole blood for assessing Se status using molecular
      biology markers.

PMID- 15465761
TI  - Increasing the protein content in a carbohydrate-free diet enhances fat loss
      during 35% but not 75% energy restriction in rats.
AB  - The purpose of the present study was to test the influence of the amount of
      protein in a carbohydrate-free diet during a weight reducing program using severe
      (75%) or more moderate (35%) energy restriction in rats. In Expt. 1, 3 groups (n
      = 6) consumed ad libitum a high-carbohydrate, low-fat diet [P21C69L10 containing
      21% of energy as protein (P21), 69% carbohydrate (C69) and 10% lipids (L10)], a
      high-carbohydrate, high-fat diet (P21C34L45), or a carbohydrate-free, high-fat,
      high-protein diet (P55L45). In Expt. 2, 7 groups (n = 7) were studied. For 20 d,
      groups 1-4 consumed ad libitum diets containing macronutrients at the proportions
      indicated in their designations [P14C56L30 (control diet), P30L70, P50L50, and
      P90L10]. Groups 5-7 were pair-fed the same diets at the level of the spontaneous
      intake of the P90L10 group on the previous day (35% energy restriction). In Expt.
      3, 5 groups (n = 7) were fed 1 of the following diets for 20 d. Group 1 consumed
      the control diet (P14C56L30) ad libitum. Groups 2-5 were energy restricted to 25%
      of the daily energy intake of group 1 with diets varying in their protein and
      lipid concentrations (P14C56L30, P50L50, P70L30, and P90L10). A high-fat content
      in the diet devoid of carbohydrate did not increase energy intake and body
      adiposity and neither body weight nor body composition was significantly affected
      by the protein to lipid ratio when energy restriction was 75%; however, a protein
      content > 50% preserved lean body mass at the expense of fat mass when energy
      restriction was 35%. Our results show that the absence of carbohydrates from the
      diet induces a low energy intake and the preferential deposition of protein.

PMID- 15465762
TI  - Physiological concentrations of retinoic acid favor myeloid dendritic cell
      development over granulocyte development in cultures of bone marrow cells from
      mice.
AB  - Differentiation of hematopoietic progenitors to dendritic cells (DCs) is a
      complex, poorly understood process regulated by cytokines, colony-stimulating
      factors, growth factor receptors, and transcription factors. However, nutritional
      factors may play an important role. Vitamin A is essential for proper immune
      function and is implicated in the development of myeloid lineage cells,
      especially granulocytes. We investigated the role of vitamin A in the
      differentiation of myeloid DCs. Cultures of bone marrow cells from mice
      stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) in
      medium with reduced serum retinol demonstrated significantly decreased DC
      development compared with control cultures containing retinol. Surprisingly,
      granulocytes predominated in cultures stimulated with GM-CSF when retinol was
      depleted. The addition of all-trans or 9-cis retinoic acid to cultures depleted
      of retinol significantly restored DCs and inhibited granulocyte development. The
      DC-promoting effect of vitamin A was specific to myeloid lineage development
      stimulated by GM-CSF because vitamin A significantly inhibited DC development
      stimulated by flt-3 ligand. Vitamin A also affected DC major histocompatibility
      complex (MHC) class II and costimulatory molecule expression. In response to
      increasing concentrations of vitamin A, the expression of MHC class II decreased
      on the DC, whereas the expression of costimulatory molecules increased,
      especially CD86. Our data suggest that vitamin A favors the differentiation of
      myeloid progenitors to immature myeloid DC instead of granulocytes when dietary
      vitamin A is adequate, and that vitamin A deficiency may compromise adaptive
      immune responses that depend on myeloid DC antigen presentation.

PMID- 15465763
TI  - Vitamin A deficiency increases the in vivo development of IL-10-positive Th2
      cells and decreases development of Th1 cells in mice.
AB  - Vitamin A deficiency impairs both T helper type 1 (Th1)- and type 2 (Th2)
      mediated immune responses, although Th2 responses seem to be principally
      affected. Multiple mechanisms are involved in this immune suppression, but the
      hypothesis that deficiency affects development of Th1/Th2 memory cell phenotype
      has not been tested directly in vivo. To do so, lymphocytes from DO11.10 T cell
      receptor (TCR)-transgenic mice were transferred to vitamin A-deficient or control
      BALB/c recipients. Recipients were then immunized with the cognate peptide
      antigen for the TCR-transgenic DO11.10 T cells (OVA(323-339)). After 2-5 wk, the
      transferred OVA(323-339)-specific T cells were identified from draining lymph
      nodes with the TCR-clonotypic antibody KJ1-26, and their Th1/Th2 phenotype was
      characterized by intracellular cytokine staining after in vitro stimulation with
      phorbol myristate acetate and ionomycin. The percentage of CD4(+)KJ1-26(+) cells
      positive for IL-10 was 100% greater in vitamin A-deficient mice (3.49 +/- 0.41%;
      mean +/- SE) than in control mice (1.74 +/- 0.37%). IL-4 did not differ between
      groups. In addition, the percentages of CD4(+)KJ1-26(+) cells from vitamin A
      deficient mice that were positive for interferon (IFN)-gamma (8.8 +/- 0.73%) and
      interleukin (IL)-2 (39.5 +/- 3.1%) were both lower than the percentages in
      control mice (11.4 +/- 0.67 and 47.0 +/- 2.8%, respectively). Thus vitamin A
      deficiency, at the time of initial antigen exposure, enhances the development of
      IL-10-producing Th2 or T regulatory cells and diminishes the development of Th1
      memory cells.

PMID- 15465764
TI  - Dietary plasma protein affects the immune response of weaned rats challenged with
      S. aureus Superantigen B.
AB  - The aim of this study was to determine the potential modulatory effects of diets
      supplemented with spray-dried animal plasma (SDAP) or immunoglobulin concentrates
      (IC) on the immune response of rats challenged with Staphylococcus aureus
      enterotoxin B (SEB). Lewis rats were fed diets containing 80 g of SDAP/kg diet,
      22.7 g of IC/kg diet, or milk proteins (Control diet) from postnatal d 21
      (weaning) for 14 d. On d 30 and 33, rats were given SEB (0.5 mg/kg body weight;
      i.p.). Organized gut-associated lymphoid tissue (GALT) populations, intestinal
      secretion, mucosal and serum immunoglobulin concentrations, and neutrophil
      infiltration were studied. On d 35, blood was collected under anesthesia and
      samples of intestinal mucosa, Peyer's patches, mesenteric lymph nodes (MLN), and
      spleen were taken. SEB increased the water content of feces, which was prevented
      by diets containing either SDAP (P < 0.002) or IC (P < 0.001), indicating that
      plasma protein-supplemented diets can reverse the SEB-induced secretory response.
      In Peyer's patches, the diet containing SDAP partially prevented the SEB-induced
      increase in T lymphocytes (P < 0.1) and reduced the percentage of activated T
      helper cells (P < 0.05). In MLN, activated T lymphocytes were increased by SEB
      but they were not affected by diet. No effects of SEB or dietary supplementation
      on mucosal IgA and serum IgA and IgG were observed. The effects of SDAP
      supplementation on the lymphocyte populations of GALT in rats challenged with SEB
      support the view that SDAP can modulate the immune response and suggest that
      plasma protein supplementation can prevent GALT from possible activation by
      luminal bacterial superantigens.

PMID- 15465765
TI  - Expression of interleukin-6 is greater in preadipocytes than in adipocytes of 3T3
      L1 cells and C57BL/6J and ob/ob mice.
AB  - Inflammation plays a major role in the development of chronic diseases such as
      cardiovascular disease and Type 2 diabetes. Further, it was demonstrated that
      obese animals and humans have significantly higher levels of circulating
      proinflammatory cytokines, such as interleukin-6 (IL-6). The aim of this study
      was to determine whether adipose tissue could be a major source of circulating IL
      6 in leptin-deficient obese (ob/ob) mice by comparing the expression of IL-6 in
      different tissues of ob/ob mice. Our secondary goal was to determine whether
      preadipocytes are the source of adipose tissue IL-6. The ob/ob mice had higher
      levels of plasma IL-6 (P < 0.05) and adipose tissue IL-6 mRNA (P < 0.05) compared
      with lean mice. Interestingly, IL-6 mRNA levels of liver and spleen were not
      different between ob/ob and lean mice, whereas adipose tissue IL-6 mRNA levels
      were higher in the ob/ob mice compared with lean mice (P < 0.05). In addition, we
      showed that IL-6 secretion from the adipose tissue stromal vascular fraction
      cells was higher than that from fully differentiated adipocytes (P < 0.001). We
      further demonstrated that 3T3-L1 preadipocytes had significantly higher levels of
      lipopolysaccharide (LPS)-stimulated IL-6 mRNA and IL-6 secretion than
      differentiated 3T3-L1 adipocytes. Taken together, these data suggest that adipose
      tissue and preadipocytes from the adipose tissue stromal vascular fraction may
      contribute significantly to the increased plasma IL-6 levels in ob/ob mice.

PMID- 15465766
TI  - Iron fortification and iron supplementation are cost-effective interventions to
      reduce iron deficiency in four subregions of the world.
AB  - Iron deficiency is the most common and widespread nutritional disorder in the
      world, affecting millions of people in both nonindustrialized and industrialized
      countries. We estimated the costs, effects, and cost-effectiveness of iron
      supplementation and iron fortification interventions in 4 regions of the world.
      The effects on population health were arrived at by using a population model
      designed to estimate the lifelong impact of iron supplementation or iron
      fortification on individuals benefiting from such interventions. The population
      model took into consideration effectiveness, patient adherence, and geographic
      coverage. Costs were based on primary data collection and on a review of the
      literature. At 95% geographic coverage, iron supplementation has a larger impact
      on population health than iron fortification. Iron supplementation would avert
      <12,500 disability adjusted life years (DALY) annually in the European subregion,
      with very low rates of adult and child mortality, to almost 2.5 million DALYs in
      the African and Southeast Asian subregions, with high rates of adult and child
      mortality. On the other hand, fortification is less costly than supplementation
      and appears to be more cost effective than iron supplementation, regardless of
      the geographic coverage of fortification. We conclude that iron fortification is
      economically more attractive than iron supplementation. However, spending the
      extra resources to implement iron supplementation is still a cost-effective
      option. The results should be interpreted with caution, because evidence of
      intervention effectiveness predominantly relates to small-scale efficacy trials,
      which may not reflect the actual effect under expected conditions.

PMID- 15465767
TI  - Fortifying food with folic acid improves folate intake in German infants,
      children, and adolescents.
AB  - Folate is a critical nutrient and programs to enhance folate intake have been
      established or are under consideration. We investigated to what extent consumers
      (C) profit from folic acid-fortified food and dietary supplements compared to
      nonconsumers (NC) of these products. A total of 6135 weighed records from 861
      subjects (47% males, 53% females, age 6 mo to 18 y) from the Dortmund Nutritional
      and Anthropometric Longitudinally Designed Study between 1990 and 2001 were
      evaluated. In 61% of the records, at least 1 item fortified with folic acid was
      reported, and in total 644 different items with a wide range of fortification
      levels were found. These were primarily commercial infant food (i.e., infant
      formula, weaning food) (44%), breakfast cereals (20%), and soft drinks (11%).
      Median dietary folate equivalents (DFEs) in NC increased from 65 and 62 microg/d
      in boys and girls at 6-12 mo of age, respectively, to 184 and 143 microg/d in
      adolescents 15-18 y of age. In C, DFEs increased from 109 and 100 microg/d in
      boys and girls at 6-12 mo of age, respectively, to 370 and 276 microg/d in
      adolescents 15-18 y of age. Irrespective of gender, NC had 50-70% the DFE intakes
      of C with a tendency for higher percentages in younger than in older children and
      adolescents. Folate intakes by male and female consumers of fortified food or
      supplements exceeded the upper levels in 1.7 and 1.2% of subjects, respectively.
      Currently, a fortification program for staple foods (e.g., grain products) does
      not seem necessary in Germany if children and adolescents consume food already
      fortified with folic acid.

PMID- 15465768
TI  - Intake of whole grains and vegetables determines the plasma enterolactone
      concentration of Danish women.
AB  - The mammalian lignan enterolactone (ENL), which is produced from dietary plant
      lignan precursors by the intestinal microflora, may protect against breast cancer
      and other hormone-dependent cancers. This cross-sectional study examined which
      variables related to diet and lifestyle were associated with high plasma
      concentrations of ENL in Danish postmenopausal women. Plasma ENL was measured by
      time-resolved fluoroimmunoassay in 857 Danish women aged 50-64 y who participated
      in a prospective cohort study. Diet was assessed using a semiquantitative FFQ,
      and background information on lifestyle was collected using a self-administered
      questionnaire. Multiple analyses of covariance were completed in two steps. The
      median plasma ENL concentration was 27 nmol/L (range 0-455 nmol/L). In covariance
      analyses, positive associations were found between consumption of cereals,
      vegetables, and beverages and plasma ENL concentration. When analyzing subgroups
      of these food groups, the associations were confined to whole-grain products,
      cabbage, leafy vegetables, and coffee. For fat and the nondietary variables,
      negative associations between BMI, smoking, and frequency of bowel movements and
      plasma ENL concentration were observed. These data show that foods high in ENL
      precursors are associated with high concentrations of ENL. Furthermore, smoking,
      frequent bowel movements, and consumption of fat seems to have a negative affect
      on the ENL concentration. In conclusion, whole grains and vegetables are the most
      important dietary providers of plant lignans for the concentration of ENL in
      Danish postmenopausal women, and if ENL is found to protect against cancer or
      heart disease, the intake of whole grains and vegetables should be increased.

PMID- 15465769
TI  - The anticarcinogenic effect of trans-11 18:1 is dependent on its conversion to
      cis-9, trans-11 CLA by delta9-desaturase in rats.
AB  - The present study was designed to determine whether the ability of vaccenic acid
      (trans-11 18:1; VA) to reduce the risk of chemically induced mammary
      carcinogenesis in rats is direct or is mediated via conversion to cis-9, trans-11
      conjugated linoleic acid (CLA). We previously reported that dietary VA caused a
      dose-dependent increase in the accumulation of CLA in the mammary fat pad, which
      was accompanied by a parallel decrease in the risk of mammary tumorigenesis.
      Specifically, our objective was to determine whether inhibiting Delta9-desaturase
      with cyclopropenoic fatty acids, supplied by sterculic oil (SO), would reverse
      the cancer-protective effect observed with a dietary supplement of VA-enriched
      butter. Female Sprague-Dawley rats were injected with a single dose of carcinogen
      (methylnitrosourea) and were fed 1 of 4 diets: 1) low VA (0.13% of diet), 2) low
      VA + SO (0.4% of diet), 3) high VA (1.60% of diet), and 4) high VA + SO. After 6
      wk, the mammary glands were evaluated histologically for the appearance of
      premalignant lesions and were stained with bromodeoxyuridine to determine the
      extent of cell proliferation, and fatty acids were analyzed in plasma, liver, and
      mammary fat pad. The VA-enriched diet increased the tissue content of CLA,
      reduced the risk of developing premalignant lesions, and decreased the
      proliferative activity of premalignant cells in the mammary gland. Treatment with
      SO reversed the effects of VA. The anticarcinogenic effect of VA is
      predominantly, perhaps exclusively, mediated through its conversion to cis-9,
      trans-11 CLA via Delta9-desaturase, and when this conversion is blocked by SO,
      the biological response to VA is attenuated.

PMID- 15465770
TI  - Low dose beta-carotene supplementation of ferrets attenuates smoke-induced lung
      phosphorylation of JNK, p38 MAPK, and p53 proteins.
AB  - We demonstrated previously that smoke exposure and/or high-dose beta-carotene
      supplementation decreases levels of retinoic acid and retinoic acid receptor beta
      (RARbeta) protein, but increase levels of c-Jun and proliferating cellular
      nuclear antigen protein in the lungs of ferrets. In contrast, low-dose beta
      carotene can prevent the decreased lung retinoic acid and the smoke-induced lung
      lesions. In the present study, we investigated whether smoke exposure and/or beta
      carotene supplementation could affect Jun N-terminal kinase (JNK), p38 mitogen
      activated protein kinase (MAPK), and p53 in the lungs of ferrets. Ferrets were
      subjected to cigarette smoke exposure and either a high or low dose of beta
      carotene (2 x 3 factorial design) for 6 mo. There were greater protein levels of
      phosphorylated JNK, p38, and c-Jun, but lower levels of MAPK phophatase-1 (MKP-1)
      in groups exposed to smoke and/or high dose beta-carotene. Both phosphorylated
      p53 and total p53 were substantially increased in the lungs of these groups. In
      contrast, low-dose beta-carotene greatly attenuated the smoke-induced
      phosphorylation of JNK, p38, c-Jun, p53, and total p53, accompanied by
      upregulated MKP-1. Smoke exposure increased MAPK kinase-4 (MKK4) phosphorylation
      regardless of beta-carotene supplementation. These data indicate that restoration
      of retinoic acid and MKP-1 by low-dose beta-carotene in the lungs of ferrets may
      prevent the smoke-induced activation of the JNK-dependent signaling pathway, p38
      MAPK, and the associated phosphorylation of p53, thereby lowering the risk of the
      smoke-related lung lesions. These data provide supportive evidence that the
      beneficial vs. detrimental effects of beta-carotene supplementation are related
      to the dosage of beta-carotene administered.

PMID- 15465771
TI  - Beef meat and blood sausage promote the formation of azoxymethane-induced mucin
      depleted foci and aberrant crypt foci in rat colons.
AB  - Red meat intake is associated with colon cancer risk. Puzzlingly, meat does not
      promote carcinogenesis in rat studies. However, we demonstrated previously that
      dietary heme promotes aberrant crypt foci (ACF) formation in rats given a low
      calcium diet. Here, we tested the hypothesis that heme-rich meats promote colon
      carcinogenesis in rats treated with azoxymethane and fed low-calcium diets (0.8
      g/kg). Three meat-based diets were formulated to contain varying concentrations
      of heme by the addition of raw chicken (low heme), beef (medium heme), or black
      pudding (blood sausage; high heme). The no-heme control diet was supplemented
      with ferric citrate and the heme control diet with hemoglobin to match iron and
      heme concentrations in the beef diet, respectively. After 100 d, colons were
      scored for ACF and mucin-depleted foci (MDF). Fecal water was assayed for
      lipoperoxides and cytotoxicity. Only diets with heme promoted the formation of
      MDF, but all meat diets promoted ACF formation. The number of MDF/colon was 0.55
      +/- 0.68 in controls, but 1.2 +/- 0.6 (P = 0.13), 1.9 +/- 1.4 (P < 0.01), and 3.0
      +/- 1.2 (P < 0.001) in chicken-, beef-, and black pudding-fed rats. MDF promotion
      by the high-heme black pudding diet was greater than that by the medium-heme beef
      diet. The number of ACF/colon was 72 +/- 16 in controls, but 91 +/- 18, 100 +/-
      13, and 103 +/- 14 in chicken-, beef-, and black pudding-fed rats (all P <
      0.001). ACF and MDF did not differ between rats fed the beef diet and those fed
      the heme control diet. MDF promotion was correlated with high fecal water
      lipoperoxides and cytotoxicity (r = 0.65, P < 0.01). This is the first study to
      show the promotion of experimental carcinogenesis by dietary meat and the
      association with heme intake.

PMID- 15465772
TI  - An in vitro digestion/Caco-2 cell culture system accurately predicts the effects
      of ascorbic acid and polyphenolic compounds on iron bioavailability in humans.
AB  - We developed a rapid in vitro digestion/Caco-2 cell culture model for assessing
      relative bioavailabilities of iron in foods and meals. The objective of the
      present study was to determine how closely our Caco-2 model reflects the human
      response. Meals described in published reports of studies on effects of varying
      levels of ascorbic acid (AA) and tannic acid (TA) on iron absorption by human
      subjects were carefully replicated. Iron absorption ratios (iron absorption from
      meals containing AA or TA divided by iron absorption from identical meals without
      these enhancers or inhibitors) were determined using the Caco-2 model. Ferritin
      formation by the Caco-2 cells was used as an indicator of iron absorption.
      Response patterns of effects of AA and TA on absorption ratios (AR) calculated
      from Caco-2 and human data were very similar: AA increased ARs in a dose-response
      manner and TAs decreased AR. The natural logs of the ARs determined in Caco-2 and
      human studies were correlated: R = 0.935 (P = 0.012) and 0.927 (P = 0.007) for AA
      and TA, respectively. When results from meals with AA and TA were pooled, a
      linear relation between the natural logs of ARs from Caco-2 and human studies was
      observed (R = 0.968, P < 0.001). We conclude that our Caco-2 model accurately
      predicts the human response to AA and TA in the meals we tested. If future work
      reproduces the precision and accuracy shown in this paper for predicting iron
      bioavailability to humans, then the implications for saving time and resources in
      iron bioavailability measurements are considerable.

PMID- 15465773
TI  - Fractional protein synthesis rates measured by an intraperitoneal injection of a
      flooding dose of L-[ring-2H5]phenylalanine in pigs.
AB  - Our objectives were to examine the effect of an i.p. injection of a flooding dose
      of l-phenylalanine (Phe) containing l-[ring-(2)H(5)]Phe on time courses of
      physiologic responses, the tracer Phe enrichments, and fractional protein
      synthesis rates (FSR) in plasma, visceral organs, and muscles. In a randomized
      complete block design, 5 blocks of 5 littermate piglets were weaned at 16 d of
      age and injected i.p. with a flooding dose of l-Phe (1.5 mmol/kg body weight) on
      d 8 postweaning under fed conditions. Tissues were collected at 15, 30, 45, 60,
      and 75 min postinjection. Plasma glucose concentration increased (cubic effect, P
      < 0.05) from 4.8 preinjection to 5.8 mmol/L 15 min postinjection and returned to
      preinjection levels thereafter. Plasma insulin concentration did not change (P >
      0.05) over time. Plasma Phe concentration increased logarithmically (P < 0.05)
      from 85 to 711 micromol/L and reached 95% of the maximum concentration 48 min
      postinjection, but no changes (P > 0.05) in tissue contents of other free amino
      acids were observed. The Phe free pools in plasma, visceral organs, and muscles
      were evenly enriched (32.3 +/- 1.4 mol%) with l-[(2)H(5)]Phe 15 min after the
      i.p. injection. The FSR in visceral organs did not change (P > 0.05), whereas
      plasma and muscle protein FSR decreased (P < 0.05) over time. We conclude that
      the i.p. injected tracer Phe rapidly distributed into plasma and intra- and
      extracellular spaces, and was effective for measuring FSR in visceral organs, but
      not in plasma and muscles of pigs.

PMID- 15465774
TI  - Metabolomics in the opening decade of the 21st century: building the roads to
      individualized health.
AB  - It is rapidly becoming possible to measure hundreds or thousands of metabolites
      in small samples of biological fluids or tissues. This makes it possible to
      assess the metabolic component of nutritional phenotypes and will allow
      individualized dietary recommendations. ASNS has to take action to ensure that
      appropriate technologies are developed and that metabolic databases are
      constructed with the right inputs and organization. The relations between diet
      and metabolomic profiles and between those profiles and health and disease must
      be established. ASNS also should consider the social implications of these
      advances and plan for their appropriate utilization.

PMID- 15465775
TI  - Controversy and statistical issues in the use of nutrient densities in assessing
      diet quality.
AB  - The use of nutrient densities, such as percentage of daily energy from added
      sugars (%E(AS)), creates serious statistical analysis and interpretation
      problems. This article examines the statistical analyses used in the September
      2002 National Academy of Sciences' Institute of Medicine (IOM) draft report on
      Dietary Reference Intakes for macronutrients. The most critical issues involve
      the use of a ratio, %E(AS), as the key analytic variable and the use of a model
      that does not properly control for total energy in the diet. Upon analyzing the
      same data from the National Health and Nutrition Examination Survey III, an
      alternative statistical approach using multiple regression to partition total
      energy into "energy from added sugars" and "energy from other sources" produced
      very different results than the IOM analysis. Whereas the IOM reported decreasing
      intakes of calcium, vitamin A, iron, and zinc with increasing %E(AS), we found
      that the association of energy from added sugars with micronutrient intake was
      inconsistent and small. Energy from other sources had a much stronger and
      consistent association with micronutrient intake. We conclude that consumption of
      added sugars has little or no association with diet quality.

PMID- 15465777
TI  - Arginine metabolism: enzymology, nutrition, and clinical significance.
      Proceedings of a symposium dedicated to the memory of Vernon R. Young. April 5-6,
      2004. Bermuda.

PMID- 15465778
TI  - Enzymes of arginine metabolism.
AB  - In mammals, L-arginine is classified as a semiessential or conditionally
      essential amino acid, depending on the developmental stage and health status of
      the individual. It can be derived from proline or glutamate, with the ultimate
      synthetic step catalyzed by argininosuccinate lyase. L-arginine is catabolized by
      arginases, nitric oxide synthases, arginine:glycine amidinotransferase, and
      possibly also by arginine decarboxylase, resulting ultimately in the production
      of urea, proline, glutamate, polyamines, nitric oxide, creatine, or agmatine.
      There is considerable diversity in tissue-specific and stimulus-dependent
      regulation of expression within this group of enzymes, and the expression of
      several of them can be regulated at transcriptional and translational levels by
      changes in the concentration of L-arginine itself. Consequently, the interplay
      among these enzymes in the regulation of specific aspects of arginine metabolism
      can be quite complex. For example, nitric oxide production can be affected by the
      interplay between nitric oxide synthases, arginases, and argininosuccinate
      synthetase. This metabolic complexity can pose challenges for analyses of
      arginine metabolism not only because L-arginine is a substrate for several
      different enzymes but also because ornithine and citrulline, key products of
      arginine metabolism, can each be produced by multiple enzymes. This overview
      highlights key features of the arginine metabolic enzymes and their interactions.

PMID- 15465779
TI  - Enzymes of the L-arginine to nitric oxide pathway.
AB  - L-Arginine is the biological precursor of nitric oxide (NO), which serves as an
      important signal and effector molecule in animals. This review summarizes some
      structure-function aspects of the mammalian nitric oxide synthases, which are
      enzymes that catalyze the oxidation of L-arginine to NO and L-citrulline. These
      include aspects related to: 1) the chemical transformations of L-arginine during
      enzyme catalysis, 2) binding of L-arginine or its structural analogs to the
      nitric oxide synthases, and 3) how L-arginine levels may affect product formation
      by the nitric oxide synthases and how this can be modulated by structural analogs
      of L-arginine.

PMID- 15465780
TI  - Plasma membrane transporters for arginine.
AB  - The supply of arginine may become rate limiting for enzymatic reactions that use
      this semiessential amino acid as a substrate (e.g., nitric oxide, agmatine,
      creatine, and urea synthesis), particularly under conditions of high demand such
      as growth, sepsis, or wound healing. In addition, arginine acts as a signaling
      molecule that regulates essential cellular functions such as protein synthesis,
      apoptosis, and growth. In the past decade, a number of carrier proteins for amino
      acids have been identified on the molecular level. They belong to different gene
      families, exhibit overlapping but distinctive substrate specificities, and can
      further be distinguished by their requirement for the cotransport or
      countertransport of inorganic ions. A number of these transporters function as
      exchangers rather than uniporters. Uptake of amino acids by these transporters
      therefore depends largely on the intracellular substrate composition. Hence,
      there is a complex crosstalk between transporters for cationic and neutral amino
      acids as well as for peptides. This article briefly reviews current knowledge
      regarding mammalian plasma membrane transporters that accept arginine as a
      substrate.

PMID- 15465781
TI  - Structure and function of arginases.
AB  - The arginases catalyze the divalent cation dependent hydrolysis of L-arginine to
      produce L-ornithine and urea. Although traditionally considered in terms of its
      role as the final enzyme of the urea cycle, the enzyme is found in a variety of
      nonhepatic tissues. These findings suggest that the enzyme may have other
      functions in addition to its role in nitrogen metabolism. High-resolution crystal
      structures have been determined for recombinant rat liver (type I) arginase and
      for recombinant human kidney (type II) arginase, their variants, and complexes
      with products and inhibitors. Each identical subunit of the trimeric enzyme
      contains an active site that lies at the bottom of a 15 A deep cleft. The 2
      essential Mn(II) ions are located at the bottom of this cleft, separated by
      approximately 3.3 A and bridged by oxygens derived from 2 aspartic acid residues
      and a solvent-derived hydroxide. This metal bridging hydroxide is proposed to be
      the nucleophile that attacks the guanidinium carbon of substrate arginine. On the
      basis of this proposed mechanism, boronic acid inhibitors of the enzyme have been
      synthesized and characterized kinetically and structurally. These inhibitors
      display slow-onset inhibition at the pH optimum of the enzyme, and are found as
      tetrahedral species at the active site, as determined by X-ray diffraction. The
      potent inhibition of arginases I and II by these compounds has not only
      delineated key enzyme-substrate interactions, but has also led to a greater
      understanding of the role of arginase in nonhepatic tissues.

PMID- 15465783
TI  - In vivo whole body and organ arginine metabolism during endotoxemia (sepsis) is
      dependent on mouse strain and gender.
AB  - Arginine metabolism involves various organs such as the kidney, the intestines,
      and the liver, which act together in an interorgan axis. Major pathways for
      arginine production are protein breakdown and de novo arginine production from
      citrulline; disposal of arginine is mainly used for protein synthesis or used by
      the enzymes arginase and nitric oxide synthase (NOS). To assess in vivo organ
      arginine metabolism under normal conditions and during endotoxemia we used a
      mouse model, and analyzed for gender and strain differences. Male and female
      inbred FVB and C57BL6/J mice were anesthetized and catheterized to study whole
      body, gut, liver, renal and muscle metabolism, using a stable isotope infusion
      protocol. Animals were treated with saline or lipopolysaccharide. Plasma arginine
      levels tended to be higher in female mice, although levels were not significantly
      different from male mice (P = 0.09). Although not all significantly different,
      whole body arginine production and arginine clearance tended to be higher in
      C57BL6/J mice (P < 0.1), while citrulline (P = 0.05), NO (P = 0.08), and de novo
      arginine (P < 0.01) production were higher in FVB mice. During endotoxemia, NO
      production increased in general (P < 0.05), while whole body arginine clearance
      increased in FVB mice, but decreased in C57BL6/J mice (P < 0.01). At the organ
      level, portal-drained viscera (PDV) arginine metabolism was higher in FVB than in
      C57BL6/J mice (P < 0.05). During endotoxemia, liver arginine metabolism decreased
      in general (P < 0.05), while strain differences existed for PDV, muscle, and
      renal arginine metabolism. In conclusion, stable isotope techniques in
      multicatheterized mice allow measurements of arginine metabolism on whole body
      and organ level. Strain and gender differences are present in arginine metabolism
      under physiological conditions and during endotoxemia.

PMID- 15465784
TI  - Clinical consequences of urea cycle enzyme deficiencies and potential links to
      arginine and nitric oxide metabolism.
AB  - Urea cycle disorders (UCD) are human conditions caused by the dysregulation of
      nitrogen transfer from ammonia nitrogen into urea. The biochemistry and the
      genetics of these disorders were well elucidated. Earlier diagnosis and improved
      treatments led to an emerging, longer-lived cohort of patients. The natural
      history of some of these disorders began to point to pathophysiological processes
      that may be unrelated to the primary cause of acute morbidity and mortality,
      i.e., hyperammonemia. Carbamyl phosphate synthetase I single nucleotide
      polymorphisms may be associated with altered vascular resistance that becomes
      clinically relevant when specific environmental stressors are present. Patients
      with argininosuccinic aciduria due to a deficiency of argininosuccinic acid lyase
      are uniquely prone to chronic hepatitis, potentially leading to cirrhosis.
      Moreover, our recent observations suggest that there may be an increased
      prevalence of essential hypertension. In contrast, hyperargininemia found in
      patients with arginase 1 deficiency is associated with pyramidal tract findings
      and spasticity, without significant hyperammonemia. An intriguing potential
      pathophysiological link is the dysregulation of intracellular arginine
      availability and its potential effect on nitric oxide (NO) metabolism. By
      combining detailed natural history studies with the development of tissue
      specific null mouse models for urea cycle enzymes and measurement of nitrogen
      flux through the cycle to urea and NO in UCD patients, we may begin to dissect
      the contribution of different sources of arginine to NO production and the
      consequences on both rare genetic and common multifactorial diseases.

PMID- 15465785
TI  - Arginine nutrition in neonatal pigs.
AB  - The concentration of arginine (an essential amino acid for neonates) in sow's
      milk is remarkably low, and thus endogenous synthesis of arginine plays a crucial
      role in maintaining arginine homeostasis in milk-fed piglets. Paradoxically,
      intestinal synthesis of citrulline from glutamine/glutamate and proline (the
      endogenous source of arginine) declines markedly in 7- to 21-d-old suckling pigs,
      compared with 1- to 3-d-old pigs. Therefore, plasma concentrations of arginine
      and its immediate precursors (ornithine and citrulline) decrease progressively by
      20-41%, whereas plasma ammonia levels increase progressively by 18-46%, between d
      3 and 14 of life. Dietary supplementation of 0.2 and 0.4% arginine to 7- to 21-d
      old pigs (artificially reared on a milk feeding system) dose dependently enhances
      the plasma arginine concentration (30 and 61%), reduces the plasma ammonia level
      (20 and 35%), and increases weight gain (28 and 66%). These compelling metabolic
      and growth data demonstrate unequivocally that arginine is insufficient for
      supporting the maximal growth in milk-fed young pigs and that this arginine
      deficiency represents a major obstacle to realizing the growth potential in
      piglets. A low concentration of mitochondrial N-acetylglutamate (an activator of
      both pyrroline-5-carboxylate synthase and carbamoylphosphate synthase-I) is
      responsible for the striking decline in the intestinal synthesis of citrulline
      and arginine during the suckling period. Accordingly, oral administration of N
      carbamoylglutamate [a metabolically stable analogue of N-acetylglutamate; 2 x 50
      mg/(kg body wt . d)] enhances plasma arginine level (68%) and weight gain (61%)
      of 4- to 14-d-old sow-reared pigs. Thus, the metabolic activation of intestinal
      citrulline and arginine synthesis provides a novel, effective means to increase
      endogenous arginine provision and therefore piglet growth (a major goal of animal
      agriculture). Our findings not only generate new fundamental knowledge about
      amino acid utilization by neonatal pigs, but they also have important practical
      implications for improving the efficiency of pork production.

PMID- 15465786
TI  - Renal arginine metabolism.
AB  - The kidney plays a major role in arginine metabolism in 3 principal ways:
      arginine synthesis, creatine synthesis, and arginine reabsorption. Appreciable
      quantities of arginine are synthesized in the kidney from citrulline produced by
      the intestine. The renal enzymes of arginine synthesis, argininosuccinate
      synthetase and argininosuccinate lyase, occur in the cells of the proximal
      tubule. The rate of arginine synthesis depends on citrulline delivery and does
      not appear to be regulated by dietary arginine availability. Renal arginine
      synthesis in humans produces approximately 2 g arginine/d, which may be compared
      to an intake, from a Western diet, of approximately 4 to 5 g/d. Spontaneous,
      nonenzymatic breakdown of creatine and creatine phosphate to creatinine causes
      the excretion of 1 to 2 g creatinine/d and requires the replacement of an
      equivalent amount of creatine from the diet and by endogenous synthesis. The
      first enzyme of creatine biosynthesis, L-arginine:glycine amidinotransferase,
      occurs in the kidney and produces guanidinoacetate, which is released into the
      renal vein. The renal output of guanidinoacetate, however, is rather low, and we
      propose that the entire pathway of creatine synthesis may also occur in the
      liver. Renal arginine reabsorption salvages approximately 3 g arginine/d. At the
      apical membrane of proximal tubular cells, arginine shares a transporter with
      lysine, ornithine, and cystine. Defects in this heteromeric transporter cause
      cystinuria, which is also characterized by urinary loss of arginine, lysine, and
      ornithine. Arginine is transported out of the proximal tubular cells at the
      basolateral membrane by another heteromeric transporter, which also transports
      lysine and ornithine. Defects in this transporter cause lysinuric protein
      intolerance.

PMID- 15465788
TI  - L-arginine and atherothrombosis.
AB  - L-arginine, the principal substrate for endothelial nitric oxide synthase, is
      oxidized to L-citrulline and nitric oxide. Endothelial dysfunction is associated
      with decreased bioactive nitric oxide production, an abnormality observed in
      atherothrombosis. Acute or chronic administration of supplemental L-arginine
      enhances endothelial nitric oxide production and improves endothelial function in
      the setting of atherothrombosis. The mechanisms by which L-arginine improves
      endothelial nitric oxide bioactivity include increased intracellular uptake via
      the high-affinity cationic transporter; substrate competition with asymmetric
      dimethylarginine, a naturally occurring inhibitor of nitric oxide synthase;
      direct antioxidant activity; stimulated release of histamine from mast cells,
      which produces a vasodilator response; decreased activity of norepinephrine,
      which promotes the effect of endogenous vasodilators including nitric oxide; and
      increased insulin secretion, which causes vasodilation. By virtue of its link to
      methyl group metabolism, supplemental L-arginine can, however, also increase the
      production of S-adenosylhomocysteine from S-adenosylmethionine through the
      methylation-dependent generation of creatine from guanidinoacetate. This reaction
      can theoretically lead to increased homocysteine synthesis from its S-adenosyl
      derivative, which itself can have adverse effects on endothelial function. The
      interrelationships among these effects of L-arginine are reviewed here, and the
      potential benefits and risks of L-arginine supplementation are discussed.

PMID- 15465789
TI  - Role of L-arginine in the pathogenesis and treatment of renal disease.
AB  - L-arginine is a semi essential amino acid and also a substrate for the synthesis
      of nitric oxide (NO), polyamines, and agmatine. These L-arginine metabolites may
      participate in the pathogenesis of renal disease and constitute the rationale for
      manipulating L-arginine metabolism as a strategy to ameliorate kidney disease.
      Modification of dietary L-arginine intake in experimental models of kidney
      diseases has been shown to have both beneficial as well as deleterious effects
      depending on the specific model studied. L-arginine supplementation in animal
      models of glomerulonephritis has been shown to be detrimental, probably by
      increasing the production of NO from increased local expression of inducible NO
      synthase (iNOS). L-arginine supplementation does not modify the course of renal
      disease in humans with chronic glomerular diseases. However, beneficial effects
      of L-arginine supplementation have been reported in several models of chronic
      kidney disease including renal ablation, ureteral obstruction, nephropathy
      secondary to diabetes, and salt-sensitive hypertension. L-arginine is reduced in
      preeclampsia and recent experimental studies indicate that L-arginine
      supplementation may be beneficial in attenuating the symptoms of preeclampsia.
      Administration of exogenous L-arginine has been shown to be protective in
      ischemic acute renal failure. In summary, the role of L-arginine in the
      pathogenesis and treatment of renal disease is not completely understood and
      remains to be established.

PMID- 15465790
TI  - L-arginine and hypertension.
AB  - Hypertension is a major healthcare problem afflicting nearly 50 million
      individuals in the United States. Despite its strong causal association with
      cardiovascular disease complications including myocardial infarction, heart
      failure, and stroke, the majority of patients with hypertension do not achieve
      optimal blood pressure control. The prevalence of hypertension is expected to
      increase with the aging population, growing obesity epidemic, and rising
      incidence of metabolic syndrome. Endothelial dysfunction and reduced nitric oxide
      (NO) bioactivity represent prominent pathophysiological abnormalities associated
      with hypertensive cardiovascular disease. Individuals with hypertension exhibit
      blunted epicardial and resistance vascular dilation to endothelium-derived nitric
      oxide (EDNO) agonists in the peripheral and coronary circulation that likely
      contributes to mechanisms of altered vascular tone in hypertension. The amino
      acid L-arginine serves as the principal substrate for vascular NO production.
      Numerous studies, though not uniformly, demonstrate a beneficial effect of acute
      and chronic L-arginine supplementation on EDNO production and endothelial
      function, and L-arginine has been shown to reduce systemic blood pressure in some
      forms of experimental hypertension. This brief review discusses the potential
      role of L-arginine in hypertension, and reviews possible mechanisms of L-arginine
      action including modulation of EDNO production, alteration of asymmetrical
      dimethylarginine (ADMA):L-arginine balance, and possible improvement of insulin
      sensitivity. In view of the rising prevalence of hypertension, randomized human
      clinical studies investigating the potential therapeutic role of L-arginine may
      be warranted.

PMID- 15465791
TI  - Novel roles for arginase in cell survival, regeneration, and translation in the
      central nervous system.
AB  - In this review the current knowledge about the arginine-degrading enzyme arginase
      and its unexpected roles in survival and regeneration in the central nervous
      system will be discussed. Recent data suggest the neuroprotective effects of
      extracellularly applied arginase can be attributed to an activation of the
      endoplasmic reticulum stress response with a consequent change of the pro
      survival gene expression profile. However, the activation of neural regeneration
      pathways caused by an upregulation of endogenous arginase I is mediated by
      polyamines, a group of arginase downstream products with widespread biological
      effects. In light of these new discoveries, there is heightened interest in the
      regulation of arginase I gene expression within the central nervous system. A
      number of transcription factors such as Sp1, C/EBP (CCATT/enhancer-binding
      protein), and CREB seem to be involved in the transcriptional control of arginase
      I and may contribute to the complex expression pattern of arginase I in distinct
      brain regions and during development. Beyond molecular mechanisms, this review
      will also include relevant clinical findings in patients with neurodegenerative
      diseases.

PMID- 15465793
TI  - Arginine metabolic enzymes, nitric oxide and infection.
AB  - Nitric oxide (NO) is synthesized from arginine by NO synthase (NOS), and the
      availability of arginine is one of the rate-limiting factors in cellular NO
      production. Citrulline that is formed as a by-product of the NOS reaction can be
      recycled to arginine by successive actions of argininosuccinate synthetase (AS)
      and argininosuccinate lyase (AL), forming the citrulline-NO cycle. AS and
      sometimes AL have been shown to be coinduced with inducible NOS (iNOS) in various
      cell types including activated macrophages, microglia, vascular smooth muscle
      cells, glial cells, neuronal PC12 cells, retinal pigment epithelial cells, and
      pancreatic beta-cells. Coinduction of endothelial NOS (eNOS), AS, and AL are
      observed in human umbilical vein endothelial cells. In contrast, arginase can
      downregulate NO production by decreasing intracellular arginine concentrations.
      iNOS and arginase activities are regulated reciprocally in macrophages by
      cytokines, and this may guarantee the efficient production of NO. In contrast,
      iNOS and arginase isoforms (type I and/or II) are coinduced in immunostimulated
      macrophages, but not in PC12 cells and glial cells. These results indicate that
      NO production is modulated by the recycling and degradation of arginine. Arginase
      also plays an important role in regulation of polyamine and proline synthesis.

PMID- 15465794
TI  - Arginine transport in catabolic disease states.
AB  - Arginine appears to be a semiessential amino acid in humans during critical
      illness. Catabolic disease states such as sepsis, injury, and cancer cause an
      increase in arginine utilization, which exceeds body production, leading to
      arginine depletion. This is aggravated by the reduced nutrient intake that is
      associated with critical illness. Arginine depletion may have negative
      consequences on tissue function under these circumstances. Nutritional regimens
      containing arginine have been shown to improve nitrogen balance and lymphocyte
      function, and stimulate arginine transport in the liver. We have studied the
      effects of stress mediators on arginine transport in vascular endothelium, liver,
      and gut epithelium. In vascular endothelium, endotoxin stimulates arginine
      uptake, an effect that is mediated by the cytokine tumor necrosis factor-alpha
      (TNF-alpha) and by the cyclo-oxygenase pathway. This TNF-alpha stimulation
      involves the activation of intracellular protein kinase C (PKC). A significant
      increase in hepatic arginine transport activity also occurs following burn injury
      and in rats with progressive malignant disease. Surgical removal of the growing
      tumor results in a normalization of the accelerated hepatic arginine transport
      within days. Chronic metabolic acidosis and sepsis individually augment
      intestinal arginine transport in rats and Caco-2 cell culture. PKC and mitogen
      activated protein kinases are involved in mediating the sepsis/acidosis
      stimulation of arginine transport. Understanding the regulation of plasma
      membrane arginine transport will enhance our knowledge of nutrition and
      metabolism in seriously ill patients and may lead to the design of improved
      nutritional support formulas.

PMID- 15465795
TI  - Arginine in asthma and lung inflammation.
AB  - Asthma, a complex chronic inflammatory pulmonary disorder, is on the rise despite
      intense ongoing research underscoring the need for new scientific inquiry. Using
      global microarray analysis, we recently discovered that asthmatic responses
      involve metabolism of arginine by arginase. We found that the cationic amino acid
      transporter (CAT)2, arginase I, and arginase II were particularly prominent among
      the allergen-induced gene transcripts. These genes are key regulators of critical
      processes associated with asthma, including airway tone, cell hyperplasia, and
      collagen deposition, respectively. Recent data suggest that arginase induction is
      not just a marker of allergic airway responses, but that arginase is involved in
      the pathogenesis of multiple aspects of disease. This review focuses on the
      current body of knowledge on L-arginine metabolism in asthma.

PMID- 15465796
TI  - Arginine and cancer.
AB  - Arginine is a dibasic, cationic, semiessential amino acid with numerous roles in
      cellular metabolism. It serves as an intermediate in the urea cycle and as a
      precursor for protein, polyamine, creatine and nitric oxide (NO) biosynthesis.
      Arginine is conditionally essential since it becomes necessary under periods of
      growth and after recovery after injury. Arginine also promotes wound healing and
      functions as a secretagogue stimulating the release of growth hormone, insulin
      like growth factor 1, insulin, and prolactin. Furthermore, arginine has several
      immunomodulatory effects such as stimulating T- and natural killer cell activity
      and influencing pro-inflammatory cytokine levels. The discover that l-arginine is
      the sole precursor for the multifunctional messenger molecule nitric oxide (NO)
      led to investigation into the role of arginine in numerous physiologic and
      pathophysiologic phenomena including cancer. Although NO was first identified in
      endothelial cells, it is now recognized to be generated by a variety of cell
      types, including several tumor cell lines and solid human tumors. Unfortunately,
      the precise role of NO in cancer is poorly understood but it may influence tumor
      initiation, promotion, and progression, tumor-cell adhesion, apoptosis
      angiogenesis, differentiation, chemosensitivity, radiosensitivity, and tumor
      induced immunosuppression. The biological effects of NO are complex and dependent
      upon numerous regulatory factors. Further research is necessary to enhance our
      understanding of the complex mechanisms that regulate NO's role in tumor biology.
      A better understanding of the role of arginine-derived NO in cancer may lead to
      novel antineoplastic and chemopreventative strategies.

PMID- 15465797
TI  - Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase,
      explains the "L-arginine paradox" and acts as a novel cardiovascular risk factor.
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). Asymmetric dimethylarginine (ADMA) is
      an endogenous competitive inhibitor of NO synthase. ADMA inhibits vascular NO
      production in concentrations found in pathophysiological conditions; ADMA also
      causes local vasoconstriction when it is infused intraarterially. Thus, elevated
      ADMA levels may explain the "L-arginine paradox," i.e., the observation that
      supplementation with exogenous L-arginine improves NO-mediated vascular functions
      in vivo, although its baseline plasma concentration is about 25-fold higher than
      the Michaelis-Menten constant K(m) of the isolated, purified endothelial NO
      synthase in vitro. The biochemical and physiological pathways related to ADMA are
      well understood: Dimethylarginines are the result of degradation of methylated
      proteins; the methyl group is derived from S-adenosylmethionine. Both ADMA and
      its regioisomer, symmetric dimethylarginine, are eliminated from the body by
      renal excretion, whereas only ADMA is metabolized via hydrolytic degradation to
      citrulline and dimethylamine by the enzyme dimethylarginine
      dimethylaminohydrolase (DDAH). DDAH activity and/or expression may therefore
      contribute to the pathogenesis of endothelial dysfunction in various diseases.
      Plasma ADMA levels are increased in 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. With
      increasing knowledge of the role of ADMA in the pathogenesis of cardiovascular
      disease, ADMA is becoming a goal for pharmacotherapeutic interventions. Among
      other potential strategies that are currently being tested, administration of L
      arginine has been shown to improve endothelium-dependent vascular functions in
      subjects with high ADMA levels. Finally, ADMA has gained clinical importance
      recently because several studies have shown that ADMA is an independent
      cardiovascular risk factor.

PMID- 15465798
TI  - Elimination of asymmetric dimethylarginine by the kidney and the liver: a link to
      the development of multiple organ failure?
AB  - Asymmetric dimethylarginine (ADMA) is a recently recognized endogenous inhibitor
      of nitric oxide production. Its role in cardiovascular disease is emerging, and
      ADMA appears to be an important causal factor in dysfunction of the vascular
      system. Several studies show that ADMA accumulates during renal failure, and ADMA
      has been identified as causing the cardiovascular complications accompanying
      renal failure. In addition to the kidney, we recently suggested an important role
      for the liver as an ADMA-eliminating organ. In a population of critically ill
      patients, hepatic failure was the most prominent determinant of ADMA
      concentration, and, notably, high ADMA concentration proved to be a strong and
      independent risk factor for intensive care unit mortality in these patients. We
      here summarize the role of both the kidney and the liver in the regulation of
      ADMA levels. In addition, the potential central role of ADMA as a causative
      factor in the development of multiple organ failure is discussed.

PMID- 15465800
TI  - Production of arginine by fermentation.
AB  - Studies on the production of L-arginine by fermentation using mutants of
      Corynebacterium (Brevibacterium), Bacillus, and Serratia have been conducted
      since the 1960s. More recently, the breeding of L-arginine production strains by
      gene recombination techniques using Escherichia coli has been investigated. To
      produce L-arginine efficiently by fermentation, it is necessary to breed strains
      with a strong biosynthetic pathway to L-arginine. Because L-arginine is
      biosynthesized from the precursor L-glutamic acid through ornithine and
      citrulline, the use of strains with a high capability for producing L-glutamic
      acid is desirable. Corynebacterium (Brevibacterium), which is well known in the
      production of L-glutamic acid, was selected as a starting strain for the breeding
      of an L-arginine producer and has been used on a commercial scale. Regarding the
      fermentation conditions, as for other amino acids, L-arginine fermentation is
      controlled by regulating pH near the neutral point. Due to its high oxygen
      requirement, L-arginine production is seriously impaired without sufficient
      oxygen. Advanced purification methods are necessary to obtain highly pure L
      arginine from the fermentation broth. After fermentation is complete, bacterial
      cells and proteins are removed by means of a membrane or centrifugation, and
      impurities are removed by means of an ion-exchange resin or activated carbon.
      Highly pure L-arginine crystals can be obtained through concentration at the end
      of the process.

PMID- 15465801
TI  - Ornithine alpha-ketoglutarate as a potent precursor of arginine and nitric oxide:
      a new job for an old friend.
AB  - Ornithine alpha-ketoglutarate (OKG) is a salt formed of 2 molecules of ornithine
      and 1 alpha-ketoglutarate. Its administration improves nutritional status in
      chronically malnourished (e.g., elderly) and acutely malnourished patients
      (especially burn and trauma patients). There is evidence that OKG activity is not
      the simple addition of the effects of ornithine (Orn) and alpha-ketoglutarate
      (alphaKG), because the presence of both moieties is required to induce the
      generation of key metabolites such as glutamine, proline, and arginine (Arg),
      whereas this does not occur when one or the other is given separately. This
      observation is related to the fact that the main feature of Orn at the whole-body
      level is to be metabolized through the Orn aminotransferase-dependent pathway,
      whereas the simultaneous administration of Orn and alphaKG saturates this
      pathway, diverting Orn toward metabolism into Arg. For years, OKG activity has
      been associated with its ability to induce the secretion of anabolic hormones,
      such as insulin and growth hormone, and to increase glutamine and polyamine
      synthesis. Recent studies using chemical inhibitors of nitric oxide synthase
      (NOS) suggest that nitric oxide derived from Arg could be partly involved in OKG
      activity. The use of genetically modified animals (i.e., knockout for NOS
      expression) is required to confirm this hypothesis.

PMID- 15465802
TI  - Enteral and parenteral arginine supplementation to improve medical outcomes in
      hospitalized patients.
AB  - The amino acid L-arginine has been administered as a single supplement to humans
      in an effort to improve the outcome of seriously ill patients. In normal
      individuals, markers of collagen biosynthesis have increased with daily oral
      doses ranging from 14 to 24.8 g of free arginine for 14 d. No clinical evidence
      of improved wound healing has been reported in the few patient studies performed
      to date. Administration of enteral, but not intravenous, arginine has been
      associated with markers of improved immune function in normal individuals and in
      some, but not all, patient groups studied. A single study in premature infants
      suggested that supplementation of L-arginine (261 mg . kg(-1) . d(-1))
      administered by both the parenteral and enteral routes decreased the incidence of
      necrotizing enterocolitis. A single study demonstrated that oral arginine
      administration in conjunction with conventional chemotherapy for active
      tuberculosis to HIV- but not HIV+ individuals enhanced treatment responses. In
      both these area, larger multicenter investigations are needed. For a difference
      to be a difference it has to make a difference. Supplementation of only L
      arginine does not to date universally show benefit, nor does it show harm. At
      this time there is no rationale for the routine supplementation of arginine alone
      to enhance recovery from serious illness. Because of the potential for harm, this
      amino acid should only be administered to critically ill patients in large doses
      under carefully monitored study conditions.

PMID- 15465803
TI  - Practical recommendations for immune-enhancing diets.
AB  - Immune-enhancing diets contain nutrients that have putative benefits, including
      arginine, (n-3) fats, glutamine, nucleotides, and structured lipids. Although
      under most circumstances the systemic inflammatory response is beneficial to the
      host, improving the eventual outcome of injury, infection, or inflammation,
      excessive proinflammation (leading to cardiac, hepatic, and mitochondrial
      dysfunction) or excessive counterinflammation (leading to immune depression) can
      worsen outcome. In critically ill septic patients, the synthesis of arginine can
      be exceeded by its catabolism to nitric oxide (NO) and urea, rendering arginine
      conditionally essential. In patients with sepsis, increased production of NO
      increases serum nitrite and nitrate levels, whereas levels in patients with
      trauma and trauma with sepsis are lower than in controls. In septic patients,
      supplemental arginine might further increase NO levels and be potentially harmful
      through excessive proinflammation. However, administration of increased amounts
      of arginine might improve immune function in surgical and trauma patients by
      increasing NO production in macrophages. When the diet provides at least 1 g of
      the (n-3) fatty acids eicosapentaenoic and docosahexaenoic acid combined, 2
      series eicosanoids (prostaglandins, prostacyclins, thromboxanes) are replaced
      partially by 3-series eicosanoids, and 4-series leukotrienes are replaced
      partially by 5-series leukotrienes that are less proinflammatory. Thus, the
      effects of arginine and (n-3)-fat supplementation might be expected to be
      complementary-arginine might improve cytokine and NO production in patients with
      immunodepression, whereas (n-3) fats might be beneficial when there is excessive
      proinflammation, particularly when supplemental arginine is supplied, by reducing
      cytokine-induced eicosanoid production.

PMID- 15465804
TI  - Role of arginase in the male and female sexual arousal response.
AB  - The NO-cGMP pathway plays a key role in the male and female genital sexual
      arousal response. Nitric oxide synthase (NOS) utilizes L-arginine and oxygen as
      substrates to produce nitric oxide (NO) and citrulline. Arginase is a
      metalloenzyme that catalyzes the hydrolysis of L-arginine to produce L-ornithine
      and urea. It is proposed that arginase competes for L-arginine and reduces NOS
      activity in genital tissues, thus modulating sexual function. Using 2 transition
      state analogue inhibitors of arginase, 2(S)-Amino-6-boronohexanoic acid (ABH) and
      S-(2-boronoethyl)-L-cysteine (BEC), we have characterized arginase activity in
      penile and vaginal tissue. Neither of these inhibitors has activity against NOS.
      Thus, ABH and BEC are useful compounds for examining the role of arginase in
      genital tissue physiology, without directly influencing NOS activity. We present
      data to suggest that arginase may regulate NO production by competing for
      endogenous pools of L-arginine. In this fashion, arginase is an indirect
      regulator of penile and vaginal blood flow and specific arginase inhibitors may
      improve genital blood flow during sexual arousal. As evidenced by the
      upregulation of arginase in specific disease states, its distribution in the
      vagina, and its modulation by sex steroid hormones, this enzyme may also
      participate in numerous other physiological and pathophysiological processes,
      such as tissue growth, fibrosis, and immune function.

PMID- 15465805
TI  - Arginine and endothelial and vascular health.
AB  - The vascular endothelium is a crucial regulator of vascular function and
      homeostasis. Nitric oxide (NO) is an important paracrine substance released by
      the endothelium to regulate vasomotor tone. Risk factors for atherosclerosis, as
      well as atherosclerosis per se, are associated with endothelial dysfunction and
      decreased bioavailablilty of NO. Indeed, endothelial dysfunction is integral to
      the pathogenesis of atherosclerosis and other cardiovascular diseases. Moreover,
      endothelial dysfunction relates to an increased risk of adverse cardiovascular
      outcomes. L-Arginine is an essential amino acid required by the constitutive
      enzyme, endothelial NO oxide synthase (eNOS), to produce NO. Administration of L
      arginine improves endothelial function in animal models and in humans with
      hypercholesterolemia and with atherosclerosis. Clinical trials to date support
      potential clinical applications of L-arginine in the treatment of coronary artery
      disease and peripheral arterial disease, as well as in the prevention of in-stent
      restenosis. The mechanism of benefit of L-arginine on endothelial function is
      unclear, because intracellular concentrations of L-arginine far exceed that
      required by eNOS. One potential explanation of this "arginine paradox" is that L
      arginine restores endothelial function in atherosclerotic patients, in whom there
      are elevated levels of asymmetric dimethylarginine, an endogenous inhibitor of
      eNOS. Given the promising findings of early studies of L-arginine as a potential
      therapy for cardiovascular disorders, large-scale clinical trials are warranted.

PMID- 15465806
TI  - Potential ergogenic effects of arginine and creatine supplementation.
AB  - The rationale for the use of nutritional supplements to enhance exercise capacity
      is based on the assumption that they will confer an ergogenic effect above and
      beyond that afforded by regular food ingestion alone. The proposed or advertised
      ergogenic effect of many supplements is based on a presumptive metabolic pathway
      and may not necessarily translate to quantifiable changes in a variable as
      broadly defined as exercise performance. L-arginine is a conditionally essential
      amino acid that has received considerable attention due to potential effects on
      growth hormone secretion and nitric oxide production. In some clinical
      circumstances (e.g., burn injury, sepsis) in which the demand for arginine cannot
      be fully met by de novo synthesis and normal dietary intake, exogenous arginine
      has been shown to facilitate the maintenance of lean body mass and functional
      capacity. However, the evidence that supplemental arginine may also confer an
      ergogenic effect in normal healthy individuals is less compelling. In contrast to
      arginine, numerous studies have reported that supplementation with the arginine
      metabolite creatine facilitates an increase in anaerobic work capacity and muscle
      mass when accompanied by resistance training programs in both normal and patient
      populations. Whereas improvement in the rate of phosphocreatine resynthesis is
      largely responsible for improvements in acute work capacity, the direct effect of
      creatine supplementation on skeletal muscle protein synthesis is less clear. The
      purpose of this review is to summarize the role of arginine and its metabolite
      creatine in the context of a nutrition supplement for use in conjunction with an
      exercise stimulus in both healthy and patient populations.

PMID- 15465809
TI  - Specificity of prion assembly in vivo. [PSI+] and [PIN+] form separate structures
      in yeast.
AB  - The yeast prions [PSI+] and [PIN+] are self-propagating amyloid aggregates of the
      Gln/Asn-rich proteins Sup35p and Rnq1p, respectively. Like the mammalian PrP
      prion "strains," [PSI+] and [PIN+] exist in different conformations called
      variants. Here, [PSI+] and [PIN+] variants were used to model in vivo
      interactions between co-existing heterologous amyloid aggregates. Two levels of
      structural organization, like those previously described for [PSI+], were
      demonstrated for [PIN+]. In cells with both [PSI+] and [PIN+] the two prions
      formed separate structures at both levels. Also, the destabilization of [PSI+] by
      certain [PIN+] variants was shown not to involve alterations in the [PSI+] prion
      size. Finally, when two variants of the same prion that have aggregates with
      distinct biochemical characteristics were combined in a single cell, only one
      aggregate type was propagated. These studies demonstrate the intracellular
      organization of yeast prions and provide insight into the principles of in vivo
      amyloid assembly.

PMID- 15465810
TI  - Multiple interactions with the Rad51 recombinase govern the homologous
      recombination function of Rad54.
AB  - In eukaryotes, Rad51 and Rad54 functionally cooperate to mediate homologous
      recombination and the repair of damaged chromosomes by recombination. Rad51, the
      eukaryotic counterpart of the bacterial RecA recombinase, forms filaments on
      single-stranded DNA that are capable of pairing the bound DNA with a homologous
      double-stranded donor to yield joint molecules. Rad54 enhances the homologous DNA
      pairing reaction, and this stimulatory effect involves a physical interaction
      with Rad51. Correspondingly, the ability of Rad54 to hydrolyze ATP and introduce
      superhelical tension into covalently closed circular plasmid DNA is stimulated by
      Rad51. By controlled proteolysis, we show that the amino-terminal region of yeast
      Rad54 is rather unstructured. Truncation mutations that delete the N-terminal 113
      or 129 amino acid residues of Rad54 attenuate or ablate physical and functional
      interactions with Rad51 under physiological ionic strength, respectively.
      Surprisingly, under less stringent conditions, the Rad54 Delta129 protein can
      interact with Rad51 in affinity pull-down and functional assays. These results
      highlight the functional importance of the N-terminal Rad51 interaction domain of
      Rad54 and reveal that Rad54 contacts Rad51 through separable epitopes.

PMID- 15465811
TI  - Solution structure of the Kaposi's sarcoma-associated herpesvirus K3 N-terminal
      domain reveals a Novel E2-binding C4HC3-type RING domain.
AB  - RING domains are found in a large number of eukaryotic proteins. Most function as
      E3 ubiquitin-protein ligases, catalyzing the terminal step in the ubiquitination
      process. Structurally, these domains have been characterized as binding two zinc
      ions in a stable cross-brace motif. The tumorigenic human gamma-herpesvirus
      Kaposi's sarcoma-associated herpesvirus encodes a ubiquitin-protein ligase termed
      K3, which functions as an immune evasion molecule by ubiquitinating major
      histocompatibility complex class I. K3 possesses at its N terminus a domain
      related to cellular RING domains but with an altered zinc ligand arrangement.
      This domain was initially characterized as a plant homeodomain, a structure not
      previously known to function as an E3. Here, it is conclusively demonstrated that
      the K3 N-terminal domain is a variant member of the RING domain family and not a
      plant homeodomain. The domain is found to interact with the cellular ubiquitin
      conjugating enzymes UbcH5A to -C and UbcH13, which dock to the equivalent surface
      as on classical cellular RING domains. Interaction with UbcH13 suggests a
      possible role for K3 in catalyzing Lys(63)-linked ubiquitination.

PMID- 15465812
TI  - Biochemical regulation of mammalian AMP-activated protein kinase activity by NAD
      and NADH.
AB  - AMP-activated protein kinase (AMPK) serves as an energy-sensing protein kinase
      that is activated by a variety of metabolic stresses that lower cellular energy
      levels. When activated, AMPK modulates a network of metabolic pathways that
      result in net increased substrate oxidation, generation of reduced nucleotide
      cofactors, and production of ATP. AMPK is activated by a high AMP:ATP ratio and
      phosphorylation on threonine 172 by an upstream kinase. Recent studies suggest
      that mechanisms that do not involve changes in adenine nucleotide levels can
      activate AMPK. Another sensor of the metabolic state of the cell is the NAD/NADH
      redox potential. To test whether the redox state might have an effect on AMPK
      activity, we examined the effect of beta-NAD and NADH on this enzyme. The
      recombinant T172D-AMPK, which was mutated to mimic the phosphorylated state, was
      activated by beta-NAD in a dose-dependent manner, whereas NADH inhibited its
      activity. We explored the effect of NADH on AMPK by systematically varying the
      concentrations of ATP, NADH, peptide substrate, and AMP. Based on our findings
      and established activation of AMPK by AMP, we proposed a model for the regulation
      by NADH. Key features of this model are as follows. (a) NADH has an apparent
      competitive behavior with respect to ATP and uncompetitive behavior with respect
      to AMP resulting in improved binding constant in the presence of AMP, and (b) the
      binding of the peptide is not significantly altered by NADH. In the absence of
      AMP, the binding constant of NADH becomes higher than physiologically relevant.
      We conclude that AMPK senses both components of cellular energy status, redox
      potential, and phosphorylation potential.

PMID- 15465813
TI  - Requirements for DNA unpairing during displacement synthesis by HIV-1 reverse
      transcriptase.
AB  - DNA displacement synthesis by reverse transcriptase during retroviral replication
      is required for the production of the linear precursor to integration. The
      sensitivity of unpaired thymines to KMnO(4) oxidation was used to probe for the
      extent of DNA melting by human immunodeficiency virus, type 1 (HIV-1) reverse
      transcriptase in front of the primer terminus in model oligonucleotide-based
      displacement constructs. Unpairing of the two base pairs downstream of the primer
      (+1 and +2 positions) requires the presence of the next correct dNTP, indicating
      that DNA melting only occurs after the formation of the ternary complex with the
      enzyme tightly clamped around the DNA. The amount or extent of DNA melting is not
      significantly affected by the length of the already-displaced strand or the base
      composition of the DNA beyond the +2 position. The F61W mutant form of HIV-1
      reverse transcriptase, which is partially impaired for displacement synthesis,
      exhibits a reduction in the amount of melting at the +1 and +2 positions. These
      results demonstrate the importance of the observed melting to displacement
      synthesis and suggest that the unpairing reaction is mediated by an intimate
      association between the fingers region of the enzyme and the DNA in the closed
      clamp conformation of the protein.

PMID- 15465814
TI  - Clioquinol mediates copper uptake and counteracts copper efflux activities of the
      amyloid precursor protein of Alzheimer's disease.
AB  - The key protein in Alzheimer's disease, the amyloid precursor protein (APP), is a
      ubiquitously expressed copper-binding glycoprotein that gives rise to the Abeta
      amyloid peptide. Whereas overexpression of APP results in significantly reduced
      brain copper levels in three different lines of transgenic mice, knock-out
      animals revealed increased copper levels. A provoked rise in peripheral levels of
      copper reduced concentrations of soluble amyloid peptides and resulted in fewer
      pathogenic Abeta plaques. Contradictory evidence has been provided by the
      efficacy of copper chelation treatment with the drug clioquinol. Using a yeast
      model system, we show that adding clioquinol to the yeast culture medium
      drastically increased the intracellular copper concentration but there was no
      significant effect observed on zinc levels. This finding suggests that clioquinol
      can act therapeutically by changing the distribution of copper or facilitating
      copper uptake rather than by decreasing copper levels. The overexpression of the
      human APP or APLP2 extracellular domains but not the extracellular domain of
      APLP1 decreased intracellular copper levels. The expression of a mutant APP
      deficient for copper binding increased intracellular copper levels several-fold.
      These data uncover a novel biological function for APP and APLP2 in copper efflux
      and provide a new conceptual framework for the formerly diverging theories of
      copper supplementation and chelation in the treatment of Alzheimer's disease.

PMID- 15465815
TI  - Spred-1 negatively regulates interleukin-3-mediated ERK/mitogen-activated protein
      (MAP) kinase activation in hematopoietic cells.
AB  - Sprouty/Spred family proteins have been identified as negative regulators of
      growth factor-induced ERK/mitogen-activated protein (MAP) kinase activation.
      However, it has not been clarified whether these proteins regulate cytokine
      induced ERK activity. We found that Spred-1 is highly expressed in interleukin-3
      (IL-3)-dependent hematopoietic cell lines and bone marrow-derived mast cells. To
      investigate the roles of Spred-1 in hematopoiesis, we expressed wild-type Spred-1
      and a dominant negative form of Spred-1, DeltaC-Spred, in IL-3- and stem cell
      factor (SCF)-dependent cell lines as well as hematopoietic progenitor cells from
      mouse bone marrow by retrovirus gene transfer. In IL-3-dependent Ba/F3 cells
      expressing c-kit, forced expression of Spred-1 resulted in a reduced
      proliferation rate and ERK activation in response to not only SCF but also IL-3.
      In contrast, DeltaC-Spred augmented IL-3-induced cell proliferation and ERK
      activation. Wild-type Spred-1 inhibited colony formation of bone marrow cells in
      the presence of cytokines, whereas DeltaC-Spred-1 expression enhanced colony
      formation. Augmentation of ERK activation and proliferation in response to IL-3
      was also observed in Spred-1-deficient bone marrow-derived mast cells. These data
      suggest that Spred-1 negatively regulates hematopoiesis by suppressing not only
      SCF-induced but also IL-3-induced ERK activation.

PMID- 15465816
TI  - IRAK1 serves as a novel regulator essential for lipopolysaccharide-induced
      interleukin-10 gene expression.
AB  - Being one of the key kinases downstream of Toll-like receptors, IRAK1 has
      initially thought to be responsible for NFkappaB activation. Yet IRAK1 knock-out
      mice still exhibit NFkappaB activation upon lipopolysaccharide (LPS) challenge,
      suggesting that IRAK1 may play other un-characterized function. In this report,
      we show that IRAK1 is mainly involved in Stat3 activation and subsequent
      interleukin-10 (IL-10) gene expression. Splenocytes from IRAK1-deficient mice
      fail to exhibit LPS-induced Stat3 serine phosphorylation and IL-10 gene
      expression yet still maintain normal IL-1beta gene expression upon LPS challenge.
      Mechanistically, we observe that IRAK1 modification upon LPS challenge leads to
      its modification, nuclear distribution, and interaction with Stat3. IRAK1 can
      directly use Stat3 as a substrate and cause Stat3 serine 727 phosphorylation. In
      addition, nuclear IRAK1 binds directly with IL-10 promoter in vivo upon LPS
      treatment. Atherosclerosis patients usually have elevated serum IL-10 levels. We
      document here that IRAK1 is constitutively modified and localized in the nucleus
      in the peripheral blood mononuclear cells from atherosclerosis patients. These
      observations reveal the mechanism for the novel role of IRAK1 in the complex Toll
      like receptor signaling network and indicate that IRAK1 regulation may be
      intimately linked with the pathogenesis and/or resolution of atherosclerosis.

PMID- 15465817
TI  - Substrate interaction at an iron-sulfur face of the FeMo-cofactor during
      nitrogenase catalysis.
AB  - Nitrogenase catalyzes biological dinitrogen fixation, the reduction of N(2) to
      2NH(3). Recently, the binding site for a non-physiological alkyne substrate
      (propargyl alcohol, HC triple bond C-CH(2)OH) was localized to a specific Fe-S
      face of the FeMo-cofactor approached by the MoFe protein amino acid alpha
      70(Val). Here we provide evidence to indicate that the smaller alkyne substrate
      acetylene (HC triple bond CH), the physiological substrate dinitrogen, and its
      semi-reduced form hydrazine (H(2)N-NH(2)) interact with the same Fe-S face of the
      FeMo-cofactor. Hydrazine is a relatively poor substrate for the wild-type (alpha
      70(Val)) MoFe protein. Substitution of the alpha-70(Val) residue by an amino acid
      having a smaller side chain (alanine) dramatically enhanced hydrazine reduction
      activity. Conversely, substitution of alpha-70(Val) by an amino acid having a
      larger side chain (isoleucine) significantly lowered the capacity of the MoFe
      protein to reduce dinitrogen, hydrazine, or acetylene.

PMID- 15465818
TI  - NMR study of repair mechanism of DNA photolyase by FAD-induced paramagnetic
      relaxation enhancement.
AB  - Cyclobutane pyrimidine dimer (CPD) photolyases, which contain FAD as a cofactor,
      use light to repair CPDs. We performed structural analyses of the catalytic site
      of the Thermus thermophilus CPD photolyase-DNA complex, using FAD-induced
      paramagnetic relaxation enhancement (PRE). The distances between the tryptophan
      residues and the FAD calculated from the PRE agree well with those observed in
      the x-ray structure (with an error of <3 A). Subsequently, a single-stranded DNA
      containing 13C-labeled CPD was prepared, and the FAD-induced PRE of the NMR
      resonances from the CPD lesion in complex with the CPD photolyase was
      investigated. The distance between the FAD and the CPD calculated from the PRE is
      16 +/- 3 A. The FAD-induced PRE was also observed in the CPD photolyase-double
      stranded DNA complex. Based on these results, a model of the CPD photolyase-DNA
      complex was constructed, and the roles of Arg-201, Lys-240, Trp-247, and Trp-353
      in the CPD-repair reaction are discussed.

PMID- 15465819
TI  - Ubiquitin ligase activity of c-Cbl guides the epidermal growth factor receptor
      into clathrin-coated pits by two distinct modes of Eps15 recruitment.
AB  - We have demonstrated previously that c-Cbl requires the presence of a functional
      ubiquitin interacting motif (UIM) in Eps15 to mediate epidermal growth factor
      receptor (EGFR) endocytosis. Both the ubiquitin ligase activity of c-Cbl and the
      UIM of Eps15 were necessary for plasma membrane recruitment of Eps15 and entry of
      ligand-bound EGFR into coated pits and vesicles containing Eps15. This is
      consistent with a scenario in which ubiquitin moieties appended to activated EGFR
      complexes act as docking sites for Eps15 and thereby recruit receptors into
      clathrin coated pits. Here, we have investigated which additional structural
      features of c-Cbl are required for this process. We find that c-Cbl can guide
      ligand-bound EGFR into the Eps15 internalization route by two distinct
      mechanisms. These are either dependent on the phosphotyrosine binding domain of c
      Cbl that directly binds to the EGFR or on the region C-terminal of the Ring
      finger, which allows for indirect binding to an alternative site on the receptor.
      No strict requirement exists for either ubiquitin modified EGFR or the Cbl
      binding ubiquitination substrate CIN85 as docking site for the UIM of Eps15. Only
      in the phosphotyrosine binding-dependent pathway, the EGFR is ubiquitinated and
      may serve as a site of recruitment for Eps15. Only in this pathway, Eps15 is
      tyrosine-phosphorylated, but this appears unrelated to its capacity to
      participate in EGFR internalization.

PMID- 15465820
TI  - Role of Tyr-288 at the dioxygen reduction site of cytochrome bo studied by stable
      isotope labeling and resonance raman spectroscopy.
AB  - To explore the role of a cross-link between side chains of Tyr-288 and His-284 at
      the heme-copper binuclear center, we prepared cytochrome bo where d(4)-Tyr, 1
      [(13)C]Tyr, or 4-[(13)C]Tyr has been biosynthetically incorporated. Unexpectedly,
      the d(4)-Tyr-labeled enzyme showed a large decrease in the ubiquinol-1 oxidase
      and CO binding activities. Optical absorption and resonance Raman spectra
      identified the defect in the distal side of the heme-copper binuclear center. In
      the CO-bound d(4)-Tyr-labeled enzyme, a large fraction of the nu((Fe-C)) mode was
      shifted from the normal 520-cm(-1) band to a broad band centered around 491 cm(
      1), as found for the Y288F mutant. Our results suggested that the substitution of
      ring hydrogens of Tyr-288 with deuteriums slows down the formation of the His-Tyr
      cross-link essential for dioxygen reduction at the binuclear center.

PMID- 15465821
TI  - Role of Bach-1 in regulation of heme oxygenase-1 in human liver cells: insights
      from studies with small interfering RNAS.
AB  - Heme oxygenase-1 is an antioxidant defense enzyme that converts heme to
      biliverdin, iron, and carbon monoxide. Bach-1 is a bZip protein that forms
      heterodimers with small Maf proteins and was reported recently to down-regulate
      the HO-1 gene in mice. Using small interfering RNAs targeted to human Bach-1
      mRNA, we investigated whether modulation of human hepatic Bach-1 expression by
      small interfering (si)RNA technology influences heme oxygenase-1 gene expression.
      We found that Bach-1 siRNAs transfected into Huh-7 cells significantly reduced
      Bach-1 mRNA and protein levels approximately 80%, compared with non siRNA-treated
      cells. In contrast, transfection with the same amounts of nonspecific control
      duplexes or LaminB2-duplex did not reduce Bach-1 mRNA or protein levels,
      confirming the specificity of Bach-1 siRNA. Expression of the heme oxygenase-1
      gene in Bach-1 siRNA-transfected cells was up-regulated 7-fold, compared with
      cells without Bach-1 siRNA. The effect of increasing concentrations of heme to up
      regulate levels of heme oxygenase-1 was more pronounced when Bach-1 siRNA was
      present. Taken together, these results indicated that Bach-1 has a specific and
      selective ability to repress expression of human hepatic heme oxygenase-1.
      Silencing of Bach-1 by siRNAs is a useful method for up-regulating HO-1 gene
      expression. Exogenous heme produces additional up-regulation, beyond that
      produced by Bach-1 siRNAs, suggesting that heme does not act solely through its
      effects on Bach-1.

PMID- 15465822
TI  - A nonenzymatic modification of the amino-terminal domain of histone H3 by bile
      acid acyl adenylate.
AB  - Although it has been proposed that the secondary bile acids, deoxycholic acid and
      lithocholic acid, increase the number of aberrant crypt foci in the colon and may
      act as colon tumor promoters, there is little evidence detailing their mechanism
      of action. Histones play an important role in controlling gene expression, and
      the posttranslational modification of histones plays a role in regulation of
      intracellular signal transduction. In particular, the amino-terminal tail domain
      of histone H3 is sensitive to several posttranslational modifications, and
      acetylation of this domain changes its electrostatic environment and results in
      the loss of native folding. Therefore, we studied the modification of epsilon
      amino groups on human histone H3 by deoxycholyl adenylate, which is an active
      intermediate in deoxycholyl thioester biosynthesis. After incubation of
      recombinant human histone H3 with a smaller amount of acyl adenylate, followed by
      enzymatic digestion, the peptide fragment mixtures were analyzed by matrix
      assisted laser desorption ionization mass spectrometry. These data showed the
      formation of only one adduct fragment, which corresponded to amino acids 3-8 with
      a deoxycholate adduct, suggesting that the epsilon-amino group of Lys(4) had the
      highest reactivity. This novel modification, formation of a bile acid adduct on
      the histone H3 amino-terminal tail domain through an active acyl adenylate, may
      relate to the carcinogenesis-promoting effects of secondary bile acids.

PMID- 15465823
TI  - The interaction of covalently bound heme with the cytochrome c maturation protein
      CcmE.
AB  - The heme chaperone CcmE is a novel protein that binds heme covalently via a
      histidine residue as part of its essential function in the process of cytochrome
      c biogenesis in many bacteria as well as plant mitochondria. In the continued
      absence of a structure of the holoform of CcmE, identification of the heme
      ligands is an important step in understanding the molecular function of this
      protein and the role of covalent heme binding to CcmE during the maturation of c
      type cytochromes. In this work, we present spectroscopic data that provide
      insight into the ligation of the heme iron in the soluble domain of CcmE from
      Escherichia coli. Resonance Raman spectra demonstrated that one of the heme axial
      ligands is a histidine residue and that the other is likely to be Tyr134. In
      addition, the properties of the heme resonances of the holo-protein as compared
      with those of a form of CcmE with non-covalently bound heme provide evidence for
      the modification of one of the heme vinyl side chains by the protein, most likely
      the 2-vinyl group.

PMID- 15465824
TI  - Di-isodityrosine is the intermolecular cross-link of isodityrosine-rich extensin
      analogs cross-linked in vitro.
AB  - Extensins are cell wall hydroxyproline-rich glycoproteins that form covalent
      networks putatively involving tyrosyl and lysyl residues in cross-links catalyzed
      by one or more extensin peroxidases. The precise cross-links remain to be
      chemically identified both as network components in muro and as enzymic products
      generated in vitro with native extensin monomers as substrates. However, some
      extensin monomers contain variations within their putative cross-linking motifs
      that complicate cross-link identification. Other simpler extensins are
      recalcitrant to isolation including the ubiquitous P3-type extensin whose major
      repetitive motif, Hyp)(4)-Ser-Hyp-Ser-(Hyp)(4)-Tyr-Tyr-Tyr-Lys, is of particular
      interest, not least because its Tyr-Tyr-Tyr intramolecular isodityrosine cross
      link motifs are also putative candidates for further intermolecular cross-linking
      to form di-isodityrosine. Therefore, we designed a set of extensin analogs
      encoding tandem repeats of the P3 motif, including Tyr --> Phe and Lys --> Leu
      variations. Expression of these P3 analogs in Nicotiana tabacum cells yielded
      glycoproteins with virtually all Pro residues hydroxylated and subsequently
      arabinosylated and with likely galactosylated Ser residues. This was consistent
      with earlier analyses of P3 glycopeptides isolated from cell wall digests and the
      predictions of the Hyp contiguity hypothesis. The tyrosine-rich P3 analogs also
      contained isodityrosine, formed in vivo. Significantly, these isodityrosine
      containing analogs were further cross-linked in vitro by an extensin peroxidase
      to form the tetra-tyrosine intermolecular cross-link amino acid di-isodityrosine.
      This is the first identification of an inter-molecular cross-link amino acid in
      an extensin module and corroborates earlier suggestions that di-isodityrosine
      represents one mechanism for cross-linking extensins in muro.

PMID- 15465825
TI  - Yeast cox17 solution structure and Copper(I) binding.
AB  - Cox17 is a 69-residue cysteine-rich, copper-binding protein that has been
      implicated in the delivery of copper to the Cu(A) and Cu(B) centers of cytochrome
      c oxidase via the copper-binding proteins Sco1 and Cox11, respectively. According
      to isothermal titration calorimetry experiments, fully reduced Cox17 binds one
      Cu(I) ion with a K(a) of (6.15 +/- 5.83) x 10(6) M(-1). The solution structures
      of both apo and Cu(I)-loaded Cox17 reveal two alpha helices preceded by an
      extensive, unstructured N-terminal region. This region is reminiscent of
      intrinsically unfolded proteins. The two structures are very similar overall with
      residues in the copper-binding region becoming more ordered in Cu(I)-loaded
      Cox17. Based on the NMR data, the Cu(I) ion has been modeled as two-coordinate
      with ligation by conserved residues Cys(23) and Cys(26). This site is similar to
      those observed for the Atx1 family of copper chaperones and is consistent with
      reported mutagenesis studies. A number of conserved, positively charged residues
      may interact with complementary surfaces on Sco1 and Cox11, facilitating docking
      and copper transfer. Taken together, these data suggest that Cox17 is not only
      well suited to a copper chaperone function but is specifically designed to
      interact with two different target proteins.

PMID- 15465826
TI  - Zinc finger proteins act as transcriptional repressors of alkaloid biosynthesis
      genes in Catharanthus roseus.
AB  - In Catharanthus roseus cell suspensions, the expression of several terpenoid
      indole alkaloid biosynthetic genes, including two genes encoding strictosidine
      synthase (STR) and tryptophan decarboxylase (TDC), is coordinately induced by
      fungal elicitors such as yeast extract. To identify molecular mechanisms
      regulating the expression of these genes, a yeast one-hybrid screening was
      performed with an elicitor-responsive part of the TDC promoter. This screening
      identified three members of the Cys(2)/His(2)-type (transcription factor IIIA
      type) zinc finger protein family from C. roseus, ZCT1, ZCT2, and ZCT3. These
      proteins bind in a sequence-specific manner to the TDC and STR promoters in vitro
      and repress the activity of these promoters in trans-activation assays. In
      addition, the ZCT proteins can repress the activating activity of
      APETALA2/ethylene response-factor domain transcription factors, the ORCAs, on the
      STR promoter. The expression of the ZCT genes is rapidly induced by yeast extract
      and methyljasmonate. These results suggest that the ZCT proteins act as
      repressors in the regulation of elicitor-induced secondary metabolism in C.
      roseus.

PMID- 15465827
TI  - BCL-3 and NF-kappaB p50 attenuate lipopolysaccharide-induced inflammatory
      responses in macrophages.
AB  - Lipopolysaccharide (LPS) induces expression of tumor necrosis factor alpha
      (TNFalpha) and other pro-inflammatory cytokines in macrophages. Following its
      induction, TNFalpha gene transcription is rapidly attenuated, in part due to the
      accumulation of NF-kappaB p50 homodimers that bind to three kappaB sites in the
      TNFalpha promoter. Here we have investigated the inhibitory role of BCL-3, an
      IkappaB-like protein that interacts exclusively with p50 and p52 homodimers. BCL
      3 was induced by LPS with delayed kinetics and was associated with p50 in the
      nucleus. Forced expression of BCL-3 suppressed LPS-induced transcription from the
      TNFalpha promoter and inhibited two artificial promoters composed of
      TNFalphakappaB sites that preferentially bind p50 dimers. BCL-3-mediated
      repression was reversed by trichostatin A and was enhanced by overexpression of
      HDAC-1, indicating that transcriptional attenuation involves recruitment of
      histone deacetylase. Analysis of macrophages from p50 and BCL-3 knock-out mice
      revealed that both transcription factors negatively regulate TNFalpha expression
      and that BCL-3 inhibits IL-1alpha and IL-1beta. In contrast, induction of the
      anti-inflammatory cytokine IL-10 was reduced in BCL-3 null macrophages. BCL-3 was
      not required for the production of p50 homodimers but BCL-3 expression was
      severely diminished in p50-deficient cells. Together, these findings indicate
      that p50 and BCL-3 function as anti-inflammatory regulators in macrophages by
      attenuating transcription of pro-inflammatory cytokines and activating IL-10
      expression.

PMID- 15465828
TI  - Phosphorylation of serine 468 by GSK-3beta negatively regulates basal p65 NF
      kappaB activity.
AB  - The activity of NF-kappaB is controlled at several levels including the
      phosphorylation of the strongly transactivating p65 (RelA) subunit. However, the
      overall number of phosphorylation sites, the signaling pathways and protein
      kinases that target p65 NF-kappaB and the functional role of these
      phosphorylations are still being uncovered. Using a combination of peptide arrays
      with in vitro kinase assays we identify serine 468 as a novel phosphorylation
      site of p65 NF-kappaB. Serine 468 lies within a GSK-3beta consensus site, and
      recombinant GSK-3beta specifically phosphorylates a GST-p65-(354-551) fusion
      protein at Ser(468) in vitro. In intact cells, phosphorylation of endogenous
      Ser(468) of p65 is induced by the PP1/PP2A phosphatase inhibitor calyculin A and
      this effect is inhibited by the GSK-3beta inhibitor LiCl. Reconstitution of p65
      deficient cells with a p65 protein where serine 468 was mutated to alanine
      revealed a negative regulatory role of serine 468 for NF-kappaB activation.
      Collectively our results suggest that a GSK-3beta-PP1-dependent mechanism
      regulates phosphorylation of p65 NF-kappaB at Ser(468) in unstimulated cells and
      thereby controls the basal activity of NF-kappaB.

PMID- 15465829
TI  - Protein-tyrosine phosphatase 1B potentiates IRE1 signaling during endoplasmic
      reticulum stress.
AB  - Protein-tyrosine phosphatase 1B (PTP-1B) is the prototypic tyrosine phosphatase
      whose function in insulin signaling and metabolism is well established. Although
      the role of PTP-1B in dephosphorylating various cell surface receptor tyrosine
      kinases is clear, the mechanisms by which it modulates receptor function from the
      endoplasmic reticulum (ER) remains an enigma. Here, we provide evidence that PTP
      1B has an essential function in regulating the unfolded protein response in the
      ER compartment. The absence of PTP-1B caused impaired ER stress-induced IRE1
      signaling. More specifically, JNK activation, XBP-1 splicing, and EDEM (ER
      degradation-enhancing alpha-mannosidase-like protein) gene induction, as well as
      ER stress-induced apoptosis, were attenuated in PTP-1B knock-out mouse embryonic
      fibroblasts in response to two ER stressors, tunicamycin and azetidine-2
      carboxylic acid. We demonstrate that PTP-1B is not just a passive resident of the
      ER but on the contrary has an essential role in potentiating IRE1-mediated ER
      stress signaling pathways.

PMID- 15465830
TI  - Involvement of domain II in toxicity of anthrax lethal factor.
AB  - Anthrax lethal factor (LF) is a Zn2+ -metalloprotease that cleaves and
      inactivates mitogen-activated protein kinase kinases (MEKs). We have used site
      directed mutagenesis to identify a cluster of residues in domain II of LF that
      lie outside the active site and are required for cellular proteolytic activity
      toward MEKs. Alanine substituted for Leu293, Lys294, Leu514, Asn516, or Arg491
      caused a 10-50-fold reduction in LF toxicity. Further, whereas pairwise
      substitution of alanine for Leu514 and either Leu293, Lys294, or Arg491
      completely abrogated LF toxicity, pairwise mutation of Leu514 and Asn516 resulted
      in toxicity comparable with N516A alone. The introduction of these mutations
      reduced LF-mediated cleavage of MEK2 in cell-based assays but altered neither the
      ability of LF to bind protective antigen nor its ability to translocate across a
      membrane. Interestingly, direct in vitro measurement of LF activity indicated
      that decreased toxicity was not always accompanied by reduced proteolytic
      activity. However, mutations in this region significantly reduced the ability of
      LF to competitively inhibit B-Raf phosphorylation of MEK. These results provide
      evidence that elements of domain II are involved in the association of LF into
      productive complex with MEKs.

PMID- 15465831
TI  - A death receptor-associated anti-apoptotic protein, BRE, inhibits mitochondrial
      apoptotic pathway.
AB  - BRE, brain and reproductive organ-expressed protein, was found previously to bind
      the intracellular juxtamembrane domain of a ubiquitous death receptor, tumor
      necrosis factor receptor 1 (TNF-R1), and to down-regulate TNF-alpha-induced
      activation of NF-kappaB. Here we show that BRE also binds to another death
      receptor, Fas, and upon overexpression conferred resistance to apoptosis induced
      by TNF-alpha, anti-Fas agonist antibody, cycloheximide, and a variety of stress
      related stimuli. However, down-regulation of the endogenous BRE by small
      interfering RNA increased apoptosis to TNF-alpha, but nottoetoposide, indicating
      that the physiological antiapoptotic role of this protein is specific to death
      receptor-mediated apoptosis. We further demonstrate that BRE mediates
      antiapoptosis by inhibiting the mitochondrial apoptotic machinery but without
      translocation to the mitochondria or nucleus or down-regulation of the cellular
      level of truncated Bid. Dissociation of BRE rapidly from TNF-R1, but not from
      Fas, upon receptor ligation suggests that this protein interacts with the death
      inducing signaling complex during apoptotic induction. Increased association of
      BREwith phosphorylated, sumoylated, and ubiquitinated proteins after death
      receptor stimulation was also detected. We conclude that in contrast to the
      truncated Bid that integrates mitochondrial apoptosis to death receptor-triggered
      apoptotic cascade, BRE inhibits the integration. We propose that BRE inhibits, by
      ubiquitination-like activity, components in or proximal to the death-inducing
      signaling complexes that are necessary for activation of the mitochondria.

PMID- 15465832
TI  - HS2 enhancer function is blocked by a transcriptional terminator inserted between
      the enhancer and the promoter.
AB  - The HS2 enhancer in the beta-globin locus control region regulates transcription
      of the globin genes 10-50 kb away. How the HS2 enhancer acts over this distance
      is not clearly understood. Earlier studies show that in erythroid cells the HS2
      enhancer initiates synthesis of intergenic RNAs from sites within and downstream
      of the enhancer, and the enhancer-initiated RNAs are transcribed through the
      intervening DNA into the cis-linked promoter and gene. To investigate the
      functional significance of the enhancer-initiated transcription, here we inserted
      the lac operator sequence in the intervening DNA between the HS2 enhancer and the
      epsilon-globin promoter in reporter plasmids and integrated the plasmids into
      erythroid K562 cells expressing the lac repressor protein. We found that the
      interposed lac operator/repressor complex blocked the elongation of enhancer
      initiated transcription through the intervening DNA and drastically reduced HS2
      enhancer function as measured by the level of mRNA synthesized from the epsilon
      globin promoter. The results indicate that the tracking and transcription
      mechanism of the HS2 enhancer-assembled transcriptional machinery from the
      enhancer through the intervening DNA into the cis-linked promoter can mediate
      enhancer-promoter interaction over a long distance.

PMID- 15465836
TI  - Idiopathic impaired spermatogenesis: genetic epidemiology is unlikely to provide
      a short-cut to better understanding.
AB  - The aetiology of impaired spermatogenesis is unknown in the majority of
      subfertile men. From several studies of concordance for involuntary childlessness
      among men, we can conclude that there is a substantial familial component in male
      subfertility and that shared loci segregating through families can be assumed. We
      now know that deletions on the Y chromosome, which do not penetrate fully,
      account for some of these cases. There are good reasons to suspect that other
      cases result from mutations in genes located elsewhere in the genome. In this
      article, we discuss different approaches to unravelling the molecular basis of
      impaired spermatogenesis originating from genetic abnormalities in chromosomes
      other than the Y chromosome. Genetic mapping studies are in general a good
      approach to detect disease-causing genes that are segregating through a
      population; they can provide a shortcut to unravelling the biochemistry of a
      disease. In this paper, we explain our reasons for arguing that linkage and
      association studies are no promising means to identify the genes causing impaired
      spermatogenesis. We conclude that direct screening of candidate genes for
      mutations will be necessary to detect genes involved in impaired spermatogenesis.
      However, this approach requires studies of the biochemical pathways of normal and
      abnormal spermatogenesis. Since we have a poor understanding of these pathways,
      more research is needed into the biochemistry of spermatogenesis.

PMID- 15465835
TI  - Endometrial and subendometrial perfusion are impaired in women with unexplained
      subfertility.
AB  - BACKGROUND: We used three-dimensional power Doppler angiography (3D-PDA) to
      examine the periodic changes in endometrial development and subendometrial
      vascularity during the normal menstrual cycle in 29 women with unexplained
      subfertility and 19 controls. METHODS: 3D-PDA was performed on alternate days
      from day 3 of the cycle until ovulation and then every 4 days until menses. VOCAL
      (Virtual Organ Computer-aided AnaLysis) and shell-imaging were used to define and
      to quantify the power Doppler signal within the endometrial and subendometrial
      regions producing indices of their relative vascularity. RESULTS: Women with
      unexplained subfertility demonstrated significant changes with time (P<0.001) in
      the indices of vascularity within the endometrium and subendometrium during the
      menstrual cycle characterized by a pre-ovulatory peak and post-ovulatory fall.
      These changes mirrored those observed in the control group but were significantly
      reduced in the endometrium and subendometrium during the mid-late follicular
      phase and early luteal phase. There were no differences in endometrial thickness
      or volume between the groups or in the plasma concentrations of estradiol or
      progesterone. CONCLUSIONS: Endometrial and subendometrial vascularity are
      significantly reduced in women with unexplained subfertility during the mid-late
      follicular phase irrespective of estradiol or progesterone concentrations and
      endometrial morphometry.

PMID- 15465837
TI  - Remifentanil in the management of severe tetanus.
AB  - A 61-yr-old woman presented with severe tetanus. Her intensive care management
      was complicated by severe generalized tetanic spasms despite the use of propofol,
      midazolam, alfentanil, magnesium sulphate, and atracurium. We describe the
      management of this problem with a variable dose remifentanil infusion.

PMID- 15465833
TI  - Aldose reductase-catalyzed reduction of aldehyde phospholipids.
AB  - Oxidation of unsaturated phospholipids results in the generation of aldehyde side
      chains that remain esterified to the phospholipid backbone. Such "core" aldehydes
      elicit immune responses and promote inflammation. However, the biochemical
      mechanisms by which phospholipid aldehydes are metabolized or detoxified are not
      well understood. In the studies reported here, we examined whether aldose
      reductase (AR), which reduces hydrophobic aldehydes, metabolizes phospholipid
      aldehydes. Incubation with AR led to the reduction of 5-oxovaleroyl, 7-oxo-5
      heptenoyl, 5-hydroxy-6-oxo-caproyl, and 5-hydroxy-8-oxo-6-octenoyl phospholipids
      generated upon oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3
      phosphocholine (PAPC). The enzyme also catalyzed the reduction of phospholipid
      aldehydes generated from the oxidation of 1-alkyl, and 1-alkenyl analogs of PAPC,
      and 1-palmitoyl-2-arachidonoyl phosphatidic acid or phosphoglycerol. Aldose
      reductase catalyzed the reduction of chemically synthesized 1-palmitoyl-2-(5
      oxovaleroyl)-sn-glycero-3-phosphatidylcholine (POVPC) with a K(m) of 10 mum.
      Addition of POVPC to the culture medium led to incorporation and reduction of the
      aldehyde in COS-7 and THP-1 cells. Reduction of POVPC in these cells was
      prevented by the AR inhibitors sorbinil and tolrestat and was increased in COS-7
      cells overexpressing AR. Together, these observations suggest that AR may be a
      significant participant in the metabolism of several structurally diverse
      phospholipid aldehydes. This metabolism may be a critical regulator of the pro
      inflammatory and immunogenic effects of oxidized phospholipids.

PMID- 15465838
TI  - Intravenous anaesthesia and repetitive transcranial magnetic stimulation
      monitoring in spinal column surgery.
AB  - BACKGROUND: Transcranial magnetic stimulation with motor evoked potential
      monitoring is a non-invasive method for monitoring motor tracts during surgery.
      However, anaesthetic agents such as propofol and volatile agents reduce responses
      to single transcranial magnetic stimulation. We assessed an intravenous technique
      for anaesthesia to allow motor evoked potentials (MEPs) to be monitored using
      repetitive transcranial magnetic stimulation (rTMS). METHODS: We applied three
      pulse rTMS (TriStim) in 11 patients undergoing spinal column surgery after spinal
      column injury and recorded the latency and peak-to-peak amplitude of MEPs.
      Anaesthesia was maintained with propofol and remifentanil. RESULTS: MEPs were
      monitored successfully intraoperatively in all patients. CONCLUSIONS: It is
      possible to monitor intraoperative MEP using rTMS during anaesthesia with
      propofol and remifentanil.

PMID- 15465839
TI  - Preoperative airway evaluation using multi-slice three-dimensional computed
      tomography for a patient with severe tracheal stenosis.
AB  - A 71-yr-old female with a malignant thyroid tumour was to undergo thyroidectomy
      under general anaesthesia. Preoperative chest x-ray and plain computed tomography
      (CT) showed severe tracheal stenosis. Three-dimensional figures of the trachea
      and a virtual bronchoscopic movie were obtained from multi-slice CT to evaluate
      the stenotic region and to simulate fibroscopic tracheal intubation,
      respectively. After induction of general anaesthesia with propofol, a tracheal
      tube was successfully passed through the stenotic region under the guide of a
      fibroscope as simulated in the virtual movie. We conclude that multi-slice CT is
      useful for preoperative airway evaluation for patients with stenosis and
      distortion of the trachea.

PMID- 15465840
TI  - Prediction of fluid responsiveness in patients during cardiac surgery.
AB  - BACKGROUND: Left ventricular stroke volume variation (SVV) has been shown to be a
      predictor of fluid responsiveness in various subsets of patients. However, the
      accuracy and reliability of SVV are unproven in patients ventilated with low
      tidal volumes. METHODS: Fourteen patients were studied immediately after coronary
      artery bypass grafting (CABG). All patients were mechanically ventilated in
      pressure-controlled mode [tidal volume 7.5 (1.2) ml kg(-1)]. In addition to
      standard haemodynamic monitoring, SVV was assessed by arterial pulse contour
      analysis. Left ventricular end-diastolic area index (LVEDAI) was determined by
      transoesophageal echocardiography. A transpulmonary thermodilution technique was
      used for measurement of cardiac index (CI), stroke volume index (SVI) and
      intrathoracic blood volume index (ITBI). All variables were assessed before and
      after a volume shift induced by tilting the patients from the anti-Trendelenburg
      (30 degrees head up) to the Trendelenburg position (30 degrees head down).
      RESULTS: After the change in the Trendelenburg position, SVV decreased
      significantly, while CI, SVI, ITBI, LVEDAI, central venous pressure (CVP) and
      pulmonary artery occlusion pressure (PAOP) increased significantly. Changes in
      SVI were significantly correlated to changes in SVV (r=0.70; P<0.0001) and to
      changes in LVEDAI, ITBI, CVP and PAOP. Only prechallenge values of SVV were
      predictive of changes in SVI after change from the anti-Trendelenburg to the
      Trendelenburg position. CONCLUSIONS: In patients after CABG surgery who were
      ventilated with low tidal volumes, SVV enabled prediction of fluid responsiveness
      and assessment of the haemodynamic effects of volume loading.

PMID- 15465841
TI  - Prospective randomized controlled trial of acute normovolaemic haemodilution in
      major gastrointestinal surgery.
AB  - BACKGROUND: The efficacy of acute normovolaemic haemodilution (ANH) remains
      uncertain because of a lack of well-designed prospective randomized controlled
      trials. The aim of this study was to assess the effects of ANH on allogeneic
      transfusion, postoperative complications, and duration of stay. METHODS:
      Consecutive patients undergoing major gastrointestinal surgery were randomized to
      a planned 3-unit ANH, or no ANH. Both groups underwent identical management
      including adherence to a transfusion protocol after surgery. Outcome measures
      included the number of patients receiving allogeneic blood, complications, and
      duration of stay. RESULTS: 380 patients were screened of which 160 were included
      in the study, median age was 62 yr (range 23-90), 'ANH' n=78, 'no ANH' n=82.
      There was no significant difference between groups in the number of patients
      receiving allogeneic blood 22/78 (28%) vs 25/82 (30%), the total number of
      allogeneic units transfused (90 vs 93), complication rate, or duration of stay.
      Haemodilution significantly increased anaesthetic time, median 55 (range 15-90)
      vs 40 min (range 17-80) (P<0.001). Significantly fewer patients in the ANH group
      experienced oliguria in the immediate postoperative period 37/78 (47%) vs 55/82
      (67%) (P=0.012). The most significant factors affecting transfusion were blood
      loss, starting haemoglobin, and age. When compared with ASA-matched historical
      controls, the introduction of a transfusion protocol reduced the transfusion rate
      in colorectal patients from 136/333 (41%) to 37/138 (27%), P=0.004. CONCLUSIONS:
      In this large pragmatic study, ANH did not affect allogeneic transfusion rate in
      major gastrointestinal surgery. Preoperative haemoglobin, blood loss, and
      transfusion protocol are the key factors influencing allogeneic transfusion.

PMID- 15465842
TI  - Pulmonary vasodilator effects of norepinephrine during the development of chronic
      pulmonary hypertension in neonatal lambs.
AB  - BACKGROUND: This experimental study was performed to determine the effects of
      norepinephrine on: (i) the pulmonary vascular tone during the development of
      pulmonary hypertension (PH) in the fetus and (ii) the circulatory adaptation at
      birth after chronic intrauterine PH. METHODS: Chronically instrumented fetal
      lambs were randomized into two groups: (i) a group with PH obtained by antenatal
      partial ligation of the ductus arteriosus (DA) (n=9) and (ii) a control group
      without DA ligation (n=6). Pulmonary vascular responses to norepinephrine (1.5
      microg min(-1)) were measured in utero 7 days after surgery. At day 8 post
      surgery, after delivery, animals were ventilated for 3 h with oxygen 100%. The
      group with PH was randomly assigned to receive norepinephrine or saline. RESULTS:
      Mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were
      higher in the PH group (P<0.01). Norepinephrine-induced decrease in PVR was more
      pronounced in the PH group than in the control group (63 vs 35%, respectively;
      P<0.01). In the PH group, the decrease in PVR during mechanical ventilation was
      greater in the animals receiving norepinephrine than in the animal receiving
      saline (from 1.05 (0.12) to 0.1 (0.02) vs from 1.04 (0.1) to 0.2 (0.04) mm Hg ml(
      1) min(-1), respectively; P<0.01). After 3 h of ventilation, mean PVR in the PH
      lambs treated by norepinephrine was similar to those measured in the control
      lambs. Aortic pressure was higher in the group treated with norepinephrine.
      CONCLUSION: The data suggest that norepinephrine may improve post-natal pulmonary
      adaptation in the newborn with persistent PH both by increasing systemic vascular
      pressure and by increasing pulmonary blood flow.

PMID- 15465843
TI  - Effects of ephedrine and phenylephrine on uterine and placental circulations and
      fetal outcome following fetal hypoxaemia and epidural-induced hypotension in a
      sheep model.
AB  - BACKGROUND: Recent studies support the use of alpha-agonists during regional
      anaesthesia in uncomplicated term pregnancies. We hypothesized that ephedrine and
      phenylephrine, administered for maternal hypotension following fetal hypoxaemia,
      are equal in respect of fetal outcome. METHODS: At 117-132 days gestation,
      chronically instrumented, anaesthetized and mechanically ventilated ewes were
      randomized to receive boluses of ephedrine (n=9) or phenylephrine (n=8) for
      maternal epidural-induced hypotension after a period of fetal hypoxaemia. Uterine
      (QUtA) and placental (QUA) volume blood flows were measured with perivascular
      transit-time ultrasonic flow probes, and uterine (RUtA) and placental (RUA)
      vascular resistances were computed from volume blood flows and maternal and fetal
      mean arterial pressures. Uterine (PIUtA) and umbilical artery (PIUA) pulsatility
      indices were obtained by Doppler ultrasonography. RESULTS: Ephedrine increased
      QUtA and decreased RUtA and PIUtA from a hypotensive to baseline level and had no
      significant effect on umbilical circulation. With phenylephrine, QUtA remained
      lower (P=0.011) and RUtA higher (P=0.043) than at baseline, although PIUtA
      decreased to baseline level. PIUA increased from baseline with phenylephrine
      (P=0.007), whereas QUA decreased (P=0.050). Maternal volume expansion with
      hydroxyethyl starch decreased RUtA significantly irrespective of the vasopressor
      used. There were no significant differences in fetal blood gas values or lactate
      concentrations between the ephedrine and phenylephrine groups. CONCLUSIONS:
      Despite the more favourable effects on uterine and placental circulations of
      ephedrine over phenylephrine, no significant differences in fetal acid-base
      status or lactate concentrations were observed.

PMID- 15465844
TI  - Effects of xenon anaesthesia on intestinal oxygenation in acutely instrumented
      pigs.
AB  - BACKGROUND: Xenon is a narcotic gas that might be able to replace volatile
      anaesthetics or nitrous oxide due to its favourable pharmacological properties,
      such as providing haemodynamic stability. Intestinal oxygenation is affected by
      most volatile anaesthetics as a result of cardiodepressive effects. Reducing
      oxygenation of the gut might be a factor leading to perioperative organ
      dysfunction. This animal study was designed to assess the effects of xenon on
      intestinal oxygenation. METHODS: After ethical approval, 24 anaesthetized,
      acutely instrumented pigs were randomly assigned to three groups: nine animals
      received xenon anaesthesia with inspiratory concentrations of 0, 20, 50 and 65%
      in addition to their basic i.v. anaesthesia, nine animals served as a study
      control group, and five animals were used to assess model stability. Measurement
      of systemic and regional haemodynamic and oxygenation parameters was made 30 min
      after changing the xenon concentration. RESULTS: Xenon elicited dose-dependent
      systemic haemodynamic changes: heart rate and cardiac output decreased by 30%,
      while mean arterial pressure was stable. Superior mesenteric artery blood flow
      was lower in the xenon group. Vascular resistance of the superior mesenteric
      artery increased. The small intestinal oxygen supply decreased with increasing
      xenon concentration; the mucosal tissue oxygen partial pressure decreased but did
      not reach hypoxic (<5 mm Hg) values. Serosal tissue oxygen partial pressure was
      maintained. CONCLUSIONS: Xenon, in addition to basic i.v. anaesthesia, elicited a
      decrease in cardiac output and maintained mean arterial pressure. Intestinal
      oxygenation was maintained, although regional macrohaemodynamic perfusion
      decreased. Xenon does not impair intestinal oxygenation under physiological
      conditions.

PMID- 15465845
TI  - Does leucocyte depletion during cardiopulmonary bypass improve oxygenation
      indices in patients with mild lung dysfunction?
AB  - BACKGROUND: Leucocyte-depleting arterial line filters have not dramatically
      improved lung function after cardiopulmonary bypass (CPB), but patients with pre
      existing lung dysfunction may benefit from their use. METHODS: We randomized 32
      patients with mild lung dysfunction having elective first-time coronary
      revascularization to either a leucocyte depleting or a standard 40-mm arterial
      line filter during CPB. The alveolar arterial oxygenation index was calculated
      before and 5 min after CPB, then at 1, 2, 4, 8, and 18 h after surgery. Time to
      extubation on the ITU was recorded. Preoperative, immediate postoperative, and 24
      h postoperative chest x-rays were scored for extravascular lung water. RESULTS:
      Postoperative alveolar-arterial oxygenation indices were better in the patients
      who received leucocyte depletion during CPB (1.65+/-0.96 in the study group vs
      2.90+/-1.72 in the control group, P<0.05). The duration of postoperative
      mechanical ventilation was less in the leucocyte-depleted group (4.8+/-2.1 vs
      8.3+/-4.7 h in the control group, P<0.05). The extravascular lung water scores
      immediately postoperatively were 13.0+/-8.6 in the study group vs 19.6+/-10.8 in
      the control group (P=0.04), and at 24 h postoperatively, 9.7+/-7.7 vs 15.2+/-9.9
      for controls. CONCLUSIONS: For patients with mild lung dysfunction, a leucocyte
      depleting arterial line filter improves postoperative oxygenation, reduces
      extravascular lung water accumulation, and reduces time on artificial ventilator
      after CPB. There may be an economic argument for the routine use of leucocyte
      depleting filters for every patient during CPB.

PMID- 15465846
TI  - Acceptability to a general haematology clinic of written responses to referrals:
      questionnaire study.

PMID- 15465847
TI  - Impact of congenital colour vision deficiency on education and unintentional
      injuries: findings from the 1958 British birth cohort.

PMID- 15465848
TI  - Endometrial leptin and leptin receptor expression in women with severe/moderate
      endometriosis.
AB  - The leptin system has been implicated in reproductive function, acting at
      endocrine and paracrine levels. Recently, deregulation of this gene family has
      been linked to endometrial changes caused by endometriosis. In the present study,
      we compare the expression of leptin receptor mRNA during the pre-receptive (LH+2)
      and receptive (LH+9) phases in the eutopic endometrium from patients with
      severe/moderate endometriosis (n = 30) versus fertile controls (n = 12). In each
      patient, two endometrial samples were obtained at LH+2 and LH+9 in their natural
      cycles. When real-time quantitative fluorescent PCR was performed, an up
      regulation of OB-RL and all the isoforms investigated was observed at LH+9 versus
      LH+2 in patients with and without endometriosis. However, no difference was found
      in the expression pattern of the total leptin receptor OB-RT, or in its long OB
      RL and soluble HuB219.3 forms when the eutopic endometria of patients with
      severe/moderate endometriosis and fertile controls were compared. By means of in
      situ hybridization, total leptin receptor mRNA was localized in the luminal
      epithelium and the glands of the endometrium. The immunohistochemical analysis of
      the long form of leptin receptor was also performed in order to confirm these
      findings at the protein level. Finally, we have also shown similar leptin mRNA
      expression in both the control group and patients with endometriosis. In
      conclusion, we have not identified differences in the endometrial expression and
      localization of leptin and the leptin receptor when comparing the eutopic
      endometrium of women with severe/moderate endometriosis and fertile controls.

PMID- 15465849
TI  - Multiple displacement amplification on single cell and possible PGD applications.
AB  - Multiple displacement amplification (MDA) is a technique used in the
      amplification of very low amounts of DNA and reported to yield large quantities
      of high-quality DNA. We used MDA to amplify the whole genome directly from a
      single cell. The most common techniques used in PGD are PCR and fluorescent in
      situ hybridization (FISH). There are many limitations to these techniques
      including, the number of chromosomes diagnosed for FISH or the quality of DNA
      issued from a single cell PCR. This report shows, for the first time, use of MDA
      for single cell whole genome amplification. A total of 16 short tandem repeats
      (STRs) were amplified successfully with a similar pattern to the genomic DNA.
      Furthermore, allelic drop out (ADO) derived from MDA was assessed in 40 single
      cells by analysing (i) heterozygosity for a known beta globin mutation (IVSI-5 C
      G) and by studying (ii) the heterozygous loci present in the STRs. ADO turned out
      to be 10.25% for the beta globin gene sequencing and 5% for the fluorescent PCR
      analysis of STRs. Moreover, the amplification accuracy of MDA permitted the
      detection of trisomy 21 on a single cell using comparative genome hybridization
      array. Altogether, these data suggest that MDA can be used for single cell
      molecular karyotyping and the diagnosis of any single gene disorder in PGD.

PMID- 15465850
TI  - Interleukin-11 expression: its significance in eutopic and ectopic human
      implantation.
AB  - Embryo implantation and subsequent decidualization, trophoblast invasion and
      formation of a functional placenta are crucial for establishment and maintenance
      of pregnancy. Interleukin-11 signalling has been shown to be obligatory for
      adequate decidualization and trophoblast invasion in mice. Defects in IL-11
      signalling in mice result in trophoblast over-invasion and fetal loss. The
      pathological situation of human tubal pregnancy resembles that of IL-11Ralpha(-/
      ) mice concerning these symptoms. As our interest is focused on the human early
      pregnancy, we compared IL-11 expression at the implantation site of ectopic tubal
      pregnancy (EP) to 1st and 2nd trimester of normal intrauterine pregnancies (IP),
      and to the normal cycling endometrium. The mRNA expression of IL-11 and IL
      11Ralpha was analysed by semiquantitative RT-PCR. Protein expression was detected
      by western blotting and immunohistochemistry. IL-11Ralpha is expressed
      constitutively in all tissue specimens analysed. IL-11 is expressed predominantly
      during follicular and early luteal phase of the menstrual cycle. In IP, IL-11
      expression peaks during the 1st trimester and declines from the beginning of the
      2nd trimester onwards. In tubal abortions, IL-11 expression is reduced in
      comparison to vital EP and IP. Cultured primary endometrial and decidual
      epithelial cells were analysed for hormonal regulation of IL-11 by enzyme-linked
      immunosorbent assay and RT-PCR. IL-11 is up-regulated by estrogen and down
      regulated by progesterone. Overall, our results indicate that in humans, IL-11
      signalling is significantly involved in regulation of trophoblast invasion. In
      the case of tubal abortion, inadequate IL-11 signalling may therefore result in
      dysregulation of trophoblast invasion.

PMID- 15465851
TI  - Somatic cell apoptosis markers and pathways in human ejaculated sperm: potential
      utility as indicators of sperm quality.
AB  - In this study we extended earlier work to determine whether sperm respond to
      somatic cell apoptotic stimuli and whether apoptotic phenotypes are significant
      indicators of human sperm quality. We evaluated ejaculated sperm from fertile
      donors and subfertile patients following purification of fractions of high and
      low motility. In unstimulated conditions, caspase enzymatic activity was higher
      in motile fractions from subfertile patients than in donors, and was higher in
      low motility fractions from both groups. Staurosporine, but not a Fas ligand or
      H2O2, significantly increased caspase activity, but only in high motility
      fractions. Procaspase-3, -7 and -9 and low levels of active caspase-3, -7 and -9
      were identified by immunoblot analysis. Apoptosis-inducing factor (AIF) was
      present in all samples but poly ADP-ribose polymerase-1 (PARP-1) was not
      detected. Phosphatidylserine translocation was significantly increased only with
      H2O2 treatment. In ejaculates of both subfertile and fertile men, we demonstrated
      the presence and activation of several proteins that are key constituents of
      apoptosis-related pathways in somatic cells, which may serve as markers for sperm
      quality.

PMID- 15465853
TI  - Determination of second virial coefficient of proteins using a dual-detector cell
      for simultaneous measurement of scattered light intensity and concentration in
      SEC-HPLC.
AB  - A method is proposed for the measurement of the B22 value of proteins in aqueous
      solutions in flow-mode that utilizes a novel fabricated dual-detector cell, which
      simultaneously measures protein concentration and the corresponding scattered
      light intensity at 90 degrees , after the protein elutes from a size-exclusion
      column. Each data point on the chromatograms obtained from the light scattering
      detector and the concentration (ultraviolet) detector is converted to Rayleigh's
      ratio, Rtheta, and concentration, c, respectively. The B22 value is calculated
      from the slope of the Debye plot (Kc/Rtheta versus c) generated from a range of
      concentrations obtained from these chromatograms for a single protein injection.
      It is shown that this method provides reliable determination of the B22 values
      for such proteins as lysozyme, chymotrypsinogen, and chymotrypsin in various
      solution conditions that agree well with those reported in literature.

PMID- 15465852
TI  - Helical packing patterns in membrane and soluble proteins.
AB  - This article presents the results of a detailed analysis of helix-helix
      interactions in membrane and soluble proteins. A data set of interacting pairs of
      helices in membrane proteins of known structure was constructed and a structure
      alignment algorithm was used to identify pairs of helices in soluble proteins
      that superimpose well with pairs of helices in the membrane-protein data set.
      Most helix pairs in membrane proteins are found to have a significant number of
      structural homologs in soluble proteins, although in some cases, primarily
      involving irregular helices, no close homologs exist. An analysis of geometric
      relationships between interacting helices in the two sets of proteins identifies
      some differences in the distributions of helix length, interfacial area, packing
      angle, and distance between the polypeptide backbones. However, a subset of
      soluble-protein helix pairs that are close structural homologs to membrane
      protein helix pairs exhibits distributions that mirror those observed in membrane
      proteins. The larger average interface size and smaller distance of closest
      approach seen for helices in membrane proteins appears due in part to a relative
      enrichment of alanines and glycines, particularly as components of the AxxxA and
      GxxxG motifs. It is argued that membrane helices are not on average more tightly
      packed than helices in soluble proteins; they are simply able to approach each
      other more closely. This enables them to interact over longer distances, which
      may in turn facilitate their remaining in contact over much of the width of the
      lipid bilayer. The close structural similarity seen between some pairs of helices
      in membrane and soluble proteins suggests that packing patterns observed in
      soluble proteins may be useful in the modeling of membrane proteins. Moreover,
      there do not appear to be fundamental differences between the magnitude of the
      forces that drive helix packing in membrane and soluble proteins, suggesting that
      strategies to make membrane proteins more soluble by mutating surface residues
      are likely to encounter success, at least in some cases.

PMID- 15465854
TI  - SAXS study of the PIR domain from the Grb14 molecular adaptor: a natively
      unfolded protein with a transient structure primer?
AB  - Grb14 belongs to the Grb7 family of adapters and was identified as a negative
      regulator of insulin signal transduction. Between the PH (pleckstrin homology)
      and SH2 (Src homology 2) domains is a new binding domain implicated in the
      interaction with receptor tyrosine kinases called PIR (phosphorylated insulin
      receptor interaction region). Both PIR and SH2 domains interact with the insulin
      receptor, but their relative role varies considering the member of the Grb7
      family and the tyrosine kinase receptor. In the case of Grb14, PIR is the main
      binding domain and is sufficient to inhibit the insulin receptor kinase activity.
      We have proposed, on the basis of NMR measurements, that PIR lacks ordered
      structure and presents a high flexibility, although remaining fully active. To
      complement this first study, we have used small-angle x-ray scattering in
      solution together with a modeling approach representing the PIR domain as a chain
      of pseudo residues. Circular dichroism experiments were also performed in the
      presence of variable amounts of trifluoroethanol. These observations, together
      with an ensemble of sequence analyses and previous NMR results, all support the
      view of PIR as essentially unstructured but with a potentially structured short
      stretch encompassing residues 399-407. This stretch, which may be only structured
      transiently in the isolated molecule, could play a major role in Grb14 PIR
      binding to a biological partner by undergoing a structural transition.

PMID- 15465855
TI  - Lipid-protein interactions of integral membrane proteins: a comparative
      simulation study.
AB  - The interactions between membrane proteins and their lipid bilayer environment
      play important roles in the stability and function of such proteins. Extended (15
      20 ns) molecular dynamics simulations have been used to explore the interactions
      of two membrane proteins with phosphatidylcholine bilayers. One protein (KcsA) is
      an alpha-helix bundle and embedded in a palmitoyl oleoyl phosphatidylcholine
      bilayer; the other (OmpA) is a beta-barrel outer-membrane protein and is in a
      dimyristoyl phosphatidylcholine bilayer. The simulations enable analysis in
      detail of a number of aspects of lipid-protein interactions. In particular, the
      interactions of aromatic amphipathic side chains (i.e., Trp, Tyr) with lipid
      headgroups, and "snorkeling" interactions of basic side chains (i.e., Lys, Arg)
      with phosphate groups are explored. Analysis of the number of contacts and of H
      bonds reveal fluctuations on an approximately 1- to 5-ns timescale. There are two
      clear bands of interacting residues on the surface of KcsA, whereas there are
      three such bands on OmpA. A large number of Arg-phosphate interactions are seen
      for KcsA; for OmpA, the number of basic-phosphate interactions is smaller and
      shows more marked fluctuations with respect to time. Both classes of interaction
      occur in clearly defined interfacial regions of width approximately 1 nm.
      Analysis of lateral diffusion of lipid molecules reveals that "boundary" lipid
      molecules diffuse at about half the rate of bulk lipid. Overall, these
      simulations present a dynamic picture of lipid-protein interactions: there are a
      number of more specific interactions but even these fluctuate on an approximately
      1- to 5-ns timescale.

PMID- 15465856
TI  - Metabolic control analysis under uncertainty: framework development and case
      studies.
AB  - Information about the enzyme kinetics in a metabolic network will enable
      understanding of the function of the network and quantitative prediction of the
      network responses to genetic and environmental perturbations. Despite recent
      advances in experimental techniques, such information is limited and existing
      experimental data show extensive variation and they are based on in vitro
      experiments. In this article, we present a computational framework based on the
      well-established (log)linear formalism of metabolic control analysis. The
      framework employs a Monte Carlo sampling procedure to simulate the uncertainty in
      the kinetic data and applies statistical tools for the identification of the rate
      limiting steps in metabolic networks. We applied the proposed framework to a
      branched biosynthetic pathway and the yeast glycolysis pathway. Analysis of the
      results allowed us to interpret and predict the responses of metabolic networks
      to genetic and environmental changes, and to gain insights on how uncertainty in
      the kinetic mechanisms and kinetic parameters propagate into the uncertainty in
      predicting network responses. Some of the practical applications of the proposed
      approach include the identification of drug targets for metabolic diseases and
      the guidance for design strategies in metabolic engineering for the purposeful
      manipulation of the metabolism of industrial organisms.

PMID- 15465857
TI  - Relating microscopic charge movement to macroscopic currents: the Ramo-Shockley
      theorem applied to ion channels.
AB  - Since the discovery of gating current, electrophysiologists have studied the
      movement of charged groups within channel proteins by changing potential and
      measuring the resulting capacitive current. The relation of atomic-scale
      movements of charged groups to the gating current measured in an external
      circuit, however, is not obvious. We report here that a general solution to this
      problem exists in the form of the Ramo-Shockley theorem. For systems with
      different amounts of atomic detail, we use the theorem to calculate the gating
      charge produced by movements of protein charges. Even without calculation or
      simulation, the Ramo-Shockley theorem eliminates a class of interpretations of
      experimental results. The theorem may also be used at each time step of
      simulations to compute external current.

PMID- 15465858
TI  - Influence of the amino substituents in the interaction of ethidium bromide with
      DNA.
AB  - A key step in the rational design of new DNA binding agents is to obtain a
      complete thermodynamic characterization of small molecule-DNA interactions.
      Ethidium bromide has served as a classic DNA intercalator for more than four
      decades. This work focuses on delineating the influence(s) of the 3- and 8-amino
      substituents of ethidium on the energetic contributions and concomitant
      fluorescent properties upon DNA complex formation. Binding affinities decrease by
      an order of magnitude upon the removal of either the 3- or 8-amino substituent,
      with a further order-of-magnitude decrease in the absence of both amino groups.
      The thermodynamic binding mechanism changes from enthalpy-driven for the parent
      ethidium to entropy-driven when both amino groups are removed. Upon DNA binding,
      fluorescence enhancement is observed in the presence of either or both of the
      amino groups, likely because of more efficient fluorescence quenching through
      solvent interactions of free amino groups than when buried within the
      intercalation site. The des-amino ethidium analog exhibits fluorescence quenching
      upon binding, consistent with less efficient quenching of the chromophore through
      interactions with solvent than within the intercalation site. Determination of
      the quantum efficiencies suggests distinct differences in the environments of the
      3- and 8-amino substituents within the DNA binding site.

PMID- 15465859
TI  - Phase diagrams describing fibrillization by polyalanine peptides.
AB  - Amyloid fibrils are the structural components underlying the intra- and
      extracellular protein deposits that are associated with a variety of human
      diseases, including Alzheimer's, Parkinson's, and the prion diseases. In this
      work, we examine the thermodynamics of fibril formation using our newly-developed
      off-lattice intermediate-resolution protein model, PRIME. The model is simple
      enough to allow the treatment of large multichain systems while maintaining a
      fairly realistic description of protein dynamics when used in conjunction with
      constant-temperature discontinuous molecular dynamics, a fast alternative to
      conventional molecular dynamics. We conduct equilibrium simulations on systems
      containing 96 Ac-KA14K-NH2 peptides over a wide range of temperatures and peptide
      concentrations using the replica-exchange method. Based on measured values of the
      heat capacity, radius of gyration, and percentage of peptides that form the
      various structures, a phase diagram in the temperature-concentration plane is
      constructed delineating the regions where each structure is stable. There are
      four distinct single-phase regions: alpha-helices, fibrils, nonfibrillar beta
      sheets, and random coils; and four two-phase regions: random coils/nonfibrillar
      beta-sheets, random coils/fibrils, fibrils/nonfibrillar beta-sheets, and alpha
      helices/nonfibrillar beta-sheets. The alpha-helical region is at low temperature
      and low concentration. The nonfibrillar beta-sheet region is at intermediate
      temperatures and low concentrations and expands to higher temperatures as
      concentration is increased. The fibril region occurs at intermediate temperatures
      and intermediate concentrations and expands to lower as the peptide concentration
      is increased. The random-coil region is at high temperatures and all
      concentrations; this region shifts to higher temperatures as the concentration is
      increased.

PMID- 15465860
TI  - Kinetics and thermodynamics of lipid amphiphile exchange between lipoproteins and
      albumin in serum.
AB  - We have examined the kinetics and thermodynamics of the exchange of a fluorescent
      amphiphile derived from a phospholipid, NBD-DMPE, between serum albumin and the
      serum lipoproteins of high density (HDL2 and HDL3), LDL, and VLDL. Binding of the
      fluorescent lipid amphiphile to bovine serum albumin is characterized, at 35
      degrees C, by an equilibrium binding constant of approximately 3 x 10(6) M(-1)
      and a characteristic time < or = 0.1 s. Association of NBD-DMPE with the
      lipoprotein particles, if considered as a partitioning of amphiphile monomers
      between the aqueous phase and the lipoprotein particles, is characterized by an
      equilibrium partition coefficient between 10(5) and 10(6), being highest for LDL
      and lowest for HDL. The association of NBD-DMPE monomers with lipoprotein
      particles can be described by insertion rate constants on the order of 10(5) M(
      1) s(-1) for VLDL and LDL and 10(4) M(-1) s(-1) for HDL. The desorption rate
      constants are on the order of 10(-5) s(-1) for all particles. The study was
      performed as a function of temperature between 15 and 35 degrees C. This
      permitted the calculation of the equilibrium thermodynamic parameters (deltaG(o),
      deltaH(o), and deltaS(o)) as well as the activation parameters (deltaG++(o),
      deltaH++(o), and deltaS++(o)) for the insertion and desorption processes. The
      association equilibrium is dominated by the entropic contribution to the free
      energy in all cases. The results are discussed in relation to phospholipid and
      amphiphile exchange phenomena involving the lipoproteins.

PMID- 15465861
TI  - Aggregation of normal and sickle hemoglobin in high concentration phosphate
      buffer.
AB  - Sickle cell disease is caused by a mutant form of hemoglobin, hemoglobin S, that
      polymerizes under hypoxic conditions. The extent and mechanism of polymerization
      are thus the subject of many studies of the pathophysiology of the disease and
      potential treatment strategies. To facilitate such studies, a model system using
      high concentration phosphate buffer (1.5 M-1.8 M) has been developed. To properly
      interpret results from studies using this model it is important to understand the
      similarities and differences in hemoglobin S polymerization in the model compared
      to polymerization under physiological conditions. In this article, we show that
      hemoglobin S and normal adult hemoglobin, hemoglobin A, aggregate in high
      concentration phosphate buffer even when the concentration of hemoglobin is below
      the solubility defined for polymerization. This phenomenon was not observed using
      0.05 M phosphate buffer or in another model system we studied that uses dextran
      to enhance polymerization. We have used static light scattering, dynamic light
      scattering, and differential interference contrast microscopy to confirm
      aggregation of deoxygenated and oxygenated hemoglobins below their solubility and
      have shown that this aggregation is not observable using turbidity measurements,
      a common technique for assessing polymerization. We have also shown that the
      aggregation increases with increasing temperature in the range of 15 degrees -37
      degrees C and that it increases as the concentration of phosphate increases.
      These studies contribute to the working knowledge of how to properly apply
      studies of hemoglobin S polymerization that are conducted using the high
      phosphate model.

PMID- 15465862
TI  - A model membrane protein for binding volatile anesthetics.
AB  - Earlier work demonstrated that a water-soluble four-helix bundle protein designed
      with a cavity in its nonpolar core is capable of binding the volatile anesthetic
      halothane with near-physiological affinity (0.7 mM Kd). To create a more
      relevant, model membrane protein receptor for studying the physicochemical
      specificity of anesthetic binding, we have synthesized a new protein that builds
      on the anesthetic-binding, hydrophilic four-helix bundle and incorporates a
      hydrophobic domain capable of ion-channel activity, resulting in an amphiphilic
      four-helix bundle that forms stable monolayers at the air/water interface. The
      affinity of the cavity within the core of the bundle for volatile anesthetic
      binding is decreased by a factor of 4-3.1 mM Kd as compared to its water-soluble
      counterpart. Nevertheless, the absence of the cavity within the otherwise
      identical amphiphilic peptide significantly decreases its affinity for halothane
      similar to its water-soluble counterpart. Specular x-ray reflectivity shows that
      the amphiphilic protein orients vectorially in Langmuir monolayers at higher
      surface pressure with its long axis perpendicular to the interface, and that it
      possesses a length consistent with its design. This provides a successful
      starting template for probing the nature of the anesthetic-peptide interaction,
      as well as a potential model system in structure/function correlation for
      understanding the anesthetic binding mechanism.

PMID- 15465863
TI  - Filtering of calcium transients by the endoplasmic reticulum in pancreatic beta
      cells.
AB  - Calcium handling in pancreatic beta-cells is important for intracellular
      signaling, the control of electrical activity, and insulin secretion. The
      endoplasmic reticulum (ER) is a key organelle involved in the storage and release
      of intracellular Ca2+. Using mathematical modeling, we analyze the filtering
      properties of the ER and clarify the dual role that it plays as both a Ca2+
      source and a Ca2+ sink. We demonstrate that recent time-dependent data on the
      free Ca2+ concentration in pancreatic islets and beta-cell clusters can be
      explained with a model that uses a passive ER that takes up Ca2+ when the cell is
      depolarized and the cytosolic Ca2+ concentration is elevated, and releases Ca2+
      when the cell is repolarized and the cytosolic Ca2+ is at a lower concentration.
      We find that Ca2+-induced Ca2+ release is not necessary to explain the data, and
      indeed the model is inconsistent with the data if Ca2+-induced Ca2+ release is a
      dominating factor. Finally, we show that a three-compartment model that includes
      a subspace compartment between the ER and the plasma membrane provides the best
      agreement with the experimental Ca2+ data.

PMID- 15465864
TI  - Kinetics of protein-DNA interaction: facilitated target location in sequence
      dependent potential.
AB  - Recognition and binding of specific sites on DNA by proteins is central for many
      cellular functions such as transcription, replication, and recombination. In the
      process of recognition, a protein rapidly searches for its specific site on a
      long DNA molecule and then strongly binds this site. Here we aim to find a
      mechanism that can provide both a fast search (1-10 s) and high stability of the
      specific protein-DNA complex (Kd=10(-15)-10(-8) M). Earlier studies have
      suggested that rapid search involves sliding of the protein along the DNA. Here
      we consider sliding as a one-dimensional diffusion in a sequence-dependent rough
      energy landscape. We demonstrate that, despite the landscape's roughness, rapid
      search can be achieved if one-dimensional sliding is accompanied by three
      dimensional diffusion. We estimate the range of the specific and nonspecific DNA
      binding energy required for rapid search and suggest experiments that can test
      our mechanism. We show that optimal search requires a protein to spend half of
      its time sliding along the DNA and the other half diffusing in three dimensions.
      We also establish that, paradoxically, realistic energy functions cannot provide
      both rapid search and strong binding of a rigid protein. To reconcile these two
      fundamental requirements we propose a search-and-fold mechanism that involves the
      coupling of protein binding and partial protein folding. The proposed mechanism
      has several important biological implications for search in the presence of other
      proteins and nucleosomes, simultaneous search by several proteins, etc. The
      proposed mechanism also provides a new framework for interpretation of
      experimental and structural data on protein-DNA interactions.

PMID- 15465865
TI  - Asymmetric addition of ceramides but not dihydroceramides promotes transbilayer
      (flip-flop) lipid motion in membranes.
AB  - Transbilayer lipid motion in membranes may be important in certain physiological
      events, such as ceramide signaling. In this study, the transbilayer
      redistribution of lipids induced either by ceramide addition or by enzymatic
      ceramide generation at one side of the membrane has been monitored using pyrene
      labeled phospholipid analogs. When added in organic solution to preformed
      liposomes, egg ceramide induced transbilayer lipid motion in a dose-dependent
      way. Short-chain (C6 and C2) ceramides were less active than egg ceramide,
      whereas dihydroceramides or dioleoylglycerol were virtually inactive in promoting
      flip-flop. The same results (either positive or negative) were obtained when
      ceramides, dihydroceramides, or diacylglycerols were generated in situ through
      the action of a sphingomyelinase or of a phospholipase C. The phenomenon was
      dependent on the bilayer lipid composition, being faster in the presence of
      lipids that promote inverted phase formation, e.g., phosphatidylethanolamine and
      cholesterol; and, conversely, slower in the presence of lysophosphatidylcholine,
      which inhibits inverted phase formation. Transbilayer motion was almost
      undetectable in bilayers composed of pure phosphatidylcholine or pure
      sphingomyelin. The use of pyrene-phosphatidylserine allowed detection of flip
      flop movement induced by egg ceramide in human red blood cell membranes at a rate
      comparable to that observed in model membranes. The data suggest that when one
      membrane leaflet becomes enriched in ceramides, they diffuse toward the other
      leaflet. This is counterbalanced by lipid movement in the opposite direction, so
      that net mass transfer between monolayers is avoided. These observations may be
      relevant to the physiological mechanism of transmembrane signaling via ceramides.

PMID- 15465866
TI  - A simplified local control model of calcium-induced calcium release in cardiac
      ventricular myocytes.
AB  - Calcium (Ca2+)-induced Ca2+ release (CICR) in cardiac myocytes exhibits high gain
      and is graded. These properties result from local control of Ca2+ release.
      Existing local control models of Ca2+ release in which interactions between L
      Type Ca2+ channels (LCCs) and ryanodine-sensitive Ca2+ release channels (RyRs)
      are simulated stochastically are able to reconstruct these properties, but only
      at high computational cost. Here we present a general analytical approach for
      deriving simplified models of local control of CICR, consisting of low
      dimensional systems of coupled ordinary differential equations, from these more
      complex local control models in which LCC-RyR interactions are simulated
      stochastically. The resulting model, referred to as the coupled LCC-RyR gating
      model, successfully reproduces a range of experimental data, including L-Type
      Ca2+ current in response to voltage-clamp stimuli, inactivation of LCC current
      with and without Ca2+ release from the sarcoplasmic reticulum, voltage-dependence
      of excitation-contraction coupling gain, graded release, and the force-frequency
      relationship. The model does so with low computational cost.

PMID- 15465868
TI  - Basal sliding and the mechanics of oscillation in a mammalian sperm flagellum.
AB  - The mechanism of oscillation in cilia and flagella has been a long-standing
      mystery. This article raises the possibility of a mechanical explanation based on
      new findings relating to where in the flagellum microtubule sliding can occur-
      and where it cannot occur. All theoretical analyses of flagellar bending have
      until now made the assumption that sliding displacements at the base of the
      flagellum cannot occur. One consequence of this has been the need to accept that
      sliding must be transmitted through propagating bends, an idea that has been
      tolerated even though it becomes paradoxical if bends are the result of
      resistance to sliding. Our observations, of spermatozoa from the chinchilla, have
      led us to a contradictory view. We have shown directly, by light microscopy and
      by two methods of electron microscopy, that basal sliding does occur. Also,
      evidence from video microscopy indicates that a propagating bend cannot transmit
      sliding through it. We have analyzed a movement pattern in which the beat
      frequency increases fourfold in a phasic manner. Our analysis of this suggests
      that new bends terminate when no further sliding is possible. At this point the
      bend direction immediately reverses. That is, the flagellar beat frequency
      increases when there is a limitation to sliding. One can see directly the
      alternation in basal sliding direction under these circumstances. This suggests a
      mechanism for the initiation of a new bend in the opposite direction to the bend
      just completed: we propose that the initiating trigger is the reversal of elastic
      deformations at the base, which reverses the direction of interdoublet sliding.

PMID- 15465867
TI  - Cholesterol sensitivity and lipid raft targeting of Kir2.1 channels.
AB  - This study investigates how changes in the level of cellular cholesterol affect
      inwardly rectifying K+ channels belonging to a family of strong rectifiers
      (Kir2). In an earlier study we showed that an increase in cellular cholesterol
      suppresses endogenous K+ current in vascular endothelial cells, presumably due to
      effects on underlying Kir2.1 channels. Here we show that, indeed, cholesterol
      increase strongly suppressed whole-cell Kir2.1 current when the channels were
      expressed in a null cell line. However, cholesterol level had no effect on the
      unitary conductance and only little effect on the open probability of the
      channels. Moreover, no cholesterol effect was observed either on the total level
      of Kir2.1 protein or on its surface expression. We suggest, therefore, that
      cholesterol modulates not the total number of Kir2.1 channels in the plasma
      membrane but rather the transition of the channels between active and silent
      states. Comparing the effects of cholesterol on members of the Kir2.x family
      shows that Kir2.1 and Kir2.2 have similar high sensitivity to cholesterol, Kir2.3
      is much less sensitive, and Kir2.4 has an intermediate sensitivity. Finally, we
      show that Kir2.x channels partition virtually exclusively into Triton-insoluble
      membrane fractions indicating that the channels are targeted into cholesterol
      rich lipid rafts.

PMID- 15465869
TI  - Visualization and mechanical manipulations of individual fibrin fibers suggest
      that fiber cross section has fractal dimension 1.3.
AB  - We report protocols and techniques to image and mechanically manipulate
      individual fibrin fibers, which are key structural components of blood clots.
      Using atomic force microscopy-based lateral force manipulations we determined the
      rupture force, FR, f fibrin fibers as a function of their diameter, D, in ambient
      conditions. As expected, the rupture force increases with increasing diameter;
      however, somewhat unexpectedly, it increases as FR approximately D1.30+/-0.06.
      Moreover, using a combined atomic force microscopy-fluorescence microscopy
      instrument, we determined the light intensity, I, of single fibers, that were
      formed with fluorescently labeled fibrinogen, as a function of their diameter, D.
      Similar to the force data, we found that the light intensity, and thus the number
      of molecules per cross section, increases as I approximately D1.25+/-0.11. Based
      on these findings we propose that fibrin fibers are fractals for which the number
      of molecules per cross section increases as about D1.3. This implies that the
      molecule density varies as rhoD approximately D -0.7, i.e., thinner fibers are
      denser than thicker fibers. Such a model would be consistent with the observation
      that fibrin fibers consist of 70-80% water and only 20-30% protein, which also
      suggests that fibrin fibers are very porous.

PMID- 15465870
TI  - Imaging cells and tissues with refractive index radiology.
AB  - Can individual cells, including live cells, be imaged using hard x rays? Common
      wisdom until now required sophisticated staining techniques for this task. We
      show instead that individual cells and cell details can be detected in culture
      solution and tissues with no staining and no other contrast-enhancing
      preparation. The sample examined can be much thicker than for many other
      microscopy techniques without sacrificing the capability to resolve cells. The
      key factor in our approach is the use of a coherent synchrotron source and of
      contrast mechanisms based on the refractive index. The first successful tests
      were conducted on a variety of cell systems including skin and internal leaf
      cells, mouse neurons, rabbit fibroblast cells, and human tumor cells.

PMID- 15465871
TI  - Probing the kinetics of single molecule protein folding.
AB  - We propose an approach to integrate the theory, simulations, and experiments in
      protein-folding kinetics. This is realized by measuring the mean and high-order
      moments of the first-passage time and its associated distribution. The full
      kinetics is revealed in the current theoretical framework through these
      measurements. In the experiments, information about the statistical properties of
      first-passage times can be obtained from the kinetic folding trajectories of
      single molecule experiments (for example, fluorescence). Theoretical/simulation
      and experimental approaches can be directly related. We study in particular the
      temperature-varying kinetics to probe the underlying structure of the folding
      energy landscape. At high temperatures, exponential kinetics is observed; there
      are multiple parallel kinetic paths leading to the native state. At intermediate
      temperatures, nonexponential kinetics appears, revealing the nature of the
      distribution of local traps on the landscape and, as a result, discrete kinetic
      paths emerge. At very low temperatures, exponential kinetics is again observed;
      the dynamics on the underlying landscape is dominated by a single barrier. The
      ratio between first-passage-time moments is proposed to be a good variable to
      quantitatively probe these kinetic changes. The temperature-dependent kinetics is
      consistent with the strange kinetics found in folding dynamics experiments. The
      potential applications of the current results to single-molecule protein folding
      are discussed.

PMID- 15465872
TI  - Colicin occlusion of OmpF and TolC channels: outer membrane translocons for
      colicin import.
AB  - The interaction of colicins with target cells is a paradigm for protein import.
      To enter cells, bactericidal colicins parasitize Escherichia coli outer membrane
      receptors whose physiological purpose is the import of essential metabolites.
      Colicins E1 and E3 initially bind to the BtuB receptor, whose beta-barrel pore is
      occluded by an N-terminal globular "plug". The x-ray structure of a complex of
      BtuB with the coiled-coil BtuB-binding domain of colicin E3 did not reveal
      displacement of the BtuB plug that would allow passage of the colicin (Kurisu,
      G., S. D. Zakharov, M. V. Zhalnina, S. Bano, V. Y. Eroukova, T. I. Rokitskaya, Y.
      N. Antonenko, M. C. Wiener, and W. A. Cramer. 2003. Nat. Struct. Biol. 10:948
      954). This correlates with the inability of BtuB to form ion channels in planar
      bilayers, shown in this work, suggesting that an additional outer membrane
      protein(s) is required for colicin import across the outer membrane. The identity
      and interaction properties of this OMP were analyzed in planar bilayer
      experiments.OmpF and TolC channels in planar bilayers were occluded by colicins
      E3 and E1, respectively, from the trans-side of the membrane. Occlusion was
      dependent upon a cis-negative transmembrane potential. A positive potential
      reversibly opened OmpF and TolC channels. Colicin N, which uses only OmpF for
      entry, occludes OmpF in planar bilayers with the same orientation constraints as
      colicins E1 and E3. The OmpF recognition sites of colicins E3 and N, and the TolC
      recognition site of colicin E1, were found to reside in the N-terminal
      translocation domains. These data are considered in the context of a two-receptor
      translocon model for colicin entry into cells.

PMID- 15465873
TI  - Use-dependent potentiation of the Nav1.6 sodium channel.
AB  - Nav1.2 and Nav1.6 are two voltage-gated sodium channel isoforms that are abundant
      in the adult central nervous system. These channels are expressed in different
      cells and localized in different neuronal regions, which may reflect functional
      specialization. To examine this possibility, we compared the properties of Nav1.2
      and Nav1.6 in response to a rapid series of repetitive depolarizations. Currents
      through Nav1.6 coexpressed with beta1 demonstrated use-dependent potentiation
      during a rapid train of depolarizations. This potentiation was in contrast to the
      use-dependent decrease in current for Nav1.2 with beta1. The voltage dependence
      of potentiation correlated with the voltage dependence of activation, and it
      still occurred when fast inactivation was removed by mutation. Rapid stimulation
      accelerated a slow phase of activation in the Nav1.6 channel that had fast
      inactivation removed, resulting in faster channel activation. Although the Nav1.2
      channel with fast inactivation removed also demonstrated slightly faster
      activation, that channel showed very pronounced slow inactivation compared to
      Nav1.6. These results indicate that potentiation of Nav1.6 sodium currents
      results from faster channel activation, and that this effect is masked by slow
      inactivation in Nav1.2. The data suggest that Nav1.6 might be more resistant to
      inactivation, which might be helpful for high-frequency firing at nodes of
      Ranvier compared to Nav1.2.

PMID- 15465874
TI  - Two complementary, local excitation, global inhibition mechanisms acting in
      parallel can explain the chemoattractant-induced regulation of PI(3,4,5)P3
      response in dictyostelium cells.
AB  - Chemotaxing cells, such as Dictyostelium and mammalian neutrophils, sense shallow
      chemoattractant gradients and respond with highly polarized changes in cell
      morphology and motility. Uniform chemoattractant stimulation induces the
      transient translocations of several downstream signaling components, including
      phosphoinositide 3-kinase (PI3K), tensin homology protein (PTEN), and
      phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3). In contrast, static
      spatial chemoattractant gradients elicit the persistent, amplified localization
      of these molecules. We have proposed a model in which the response to
      chemoattractant is regulated by a balance of a local excitation and a global
      inhibition, both of which are controlled by receptor occupancy. This model can
      account for both the transient and spatial responses to chemoattractants, but
      alone does not amplify the external gradient. In this article, we develop a model
      in which parallel local excitation, global inhibition mechanisms control the
      membrane binding of PI3K and PTEN. Together, the action of these enzymes induces
      an amplified PI(3,4,5)P3 response that agrees quantitatively with experimentally
      obtained plekstrin homology-green fluorescent protein distributions in
      latrunculin-treated cells. We compare the model's performance with that of
      several mutants in which one or both of the enzymes are disrupted. The model
      accounts for the observed response to multiple, simultaneous chemoattractant cues
      and can recreate the cellular response to combinations of temporal and spatial
      stimuli. Finally, we use the model to predict the response of a cell where only a
      fraction is stimulated by a saturating dose of chemoattractant.

PMID- 15465875
TI  - A single-molecule technique to study sequence-dependent transcription pausing.
AB  - We present a technique that allows sequence-dependent analysis of transcription
      elongation using single-molecule optical trapping techniques. Observation of
      individual molecules of RNA polymerase (RNAP) allows determination of elongation
      kinetics that are difficult or impossible to accurately obtain from bulk studies,
      and provides high temporal resolution of the RNAP motion under a calibrated
      mechanical load. One limitation of previous single molecule studies was the
      difficulty in correlating the observed motion of RNAP with its actual position on
      the DNA template to better than approximately 100 bp. In this work, we improved
      the spatial precision of optical trapping studies of transcription to
      approximately 5 bp by using runoff transcription as an unambiguous marker of RNAP
      template position. This runoff method was sufficient to unequivocally locate and
      study a single known pause sequence (DeltatR2). By applying various loads to
      assist RNAP forward translocation, we specifically investigated elongation
      kinetics within this pause region and found that the dwell time at the pause
      sequence decreased with increasing assisting load. This observation is consistent
      with bulk biochemical studies that suggest RNAP reverse translocates, or
      "backtracks," at the DeltatR2 pause sequence.

PMID- 15465878
TI  - Prevalence of distress and symptom severity from the lower urinary tract in men:
      a population-based study with the DAN-PSS questionnaire.
AB  - BACKGROUND: Lower urinary tract symptoms (LUTS) are a common and costly public
      health issue. The prevalence varies greatly in published reports. The distress
      caused by each symptom is important to assess the primary care required before
      therapeutic decisions or a referral to an urologist are made. OBJECTIVES: LUTS
      are highly prevalent in men, but less is known regarding the distress caused by
      each symptom. The aim of this study was to examine symptom severity and different
      levels of distress using the Danish Prostatic Symptom Score (DAN-PSS)
      questionnaire in men affected by symptoms from the lower urinary tract. METHODS:
      The study included all men aged 41-81 years (n=504) that, 12 months earlier in a
      population-based survey, had reported stress incontinence, urgency or post
      micturition dribbling in a postal questionnaire. The DAN-PSS questionnaire was
      used to measure severity and distress from LUTS. RESULTS: In total, 311 (80%) of
      the 387 responders who reported at least one symptom experienced some level of
      distress. The most distressing symptom overall was urinary incontinence. Nine of
      10 men with storage symptoms (stress, urge and 'other' urinary incontinence)
      reported distress even if the symptom occurred only seldom. Moreover, two-thirds
      of the men with the most frequent symptom, post-micturition dribbling,
      characterized their symptom as moderate or severe; the most distressing voiding
      symptom was weak stream. In general, LUTS were well tolerated. CONCLUSION: Urge
      incontinence was the most distressing LUTS even when occurring only seldom. The
      DAN-PSS questionnaire may be a potentially useful tool for health professionals
      to identify patients with pronounced distress from LUTS to offer therapeutic and
      nursing care on the relevant level.

PMID- 15465879
TI  - Anticoagulant treatment of patients with chronic atrial fibrillation in primary
      health care in Sweden--a retrospective study of incidence and quality in a
      registered population.
AB  - BACKGROUND: The number of patients receiving anticoagulant treatment is
      increasing. Chronic atrial fibrillation is the most common treatment diagnosis.
      The literature indicates a variable level of treatment control. Estimates of time
      within the therapeutic range have been recommended as a measurement of quality.
      Electronic patient records are providing clinical data that are useful for audits
      concerning anticoagulant treatment in real-life practice. OBJECTIVE: Our aim was
      to assess warfarin treatment for chronic atrial fibrillation in primary health
      care with regard to prevalence, incidence and quality. METHODS: A 2 year
      retrospective study was carried out of electronic patient records up to April
      2002 in primary health care in Stockholm, including 12 primary health care
      centres with a registered population of 203 407. Main outcome measures were the
      number of new patients on wafarin treatment for chronic atrial fibrillation, and
      time within the therapeutic prothrombin range in the first 90 days of treatment
      using a linear interpolation method. RESULTS: In total, 827 patients were on
      warfarin treatment for chronic atrial fibrillation, giving a prevalence of 0.41%.
      Of these, 144 patients (study group) started treatment with warfarin for chronic
      atrial fibrillation during the study period, giving a yearly incidence of 0.07%.
      Their mean age was 73.1 years and 61.1% were men. There were 1721 prothrombin
      monitoring episodes registered in the first 90 days of treatment, on average once
      a week per patient. The average proportion of time within the therapeutic range
      was 54.1% (95% confidence interval (CI) 50.1-58.1), and the proportion of
      therapeutic tests was 50.2% (95% CI 47.8-52.6). CONCLUSIONS: During the first,
      second and third months of warfarin treatment for chronic atrial fibrillation,
      patients were outside the therapeutic range time nearly half the time. There was
      a gender difference favouring men regarding initiation of treatment.

PMID- 15465880
TI  - The changing face of primary care: the second Dutch national survey.

PMID- 15465881
TI  - Patient consent rates for video-recording.

PMID- 15465882
TI  - Does a patient-held health record give rise to lifestyle changes? A study in
      clinical practice.
AB  - BACKGROUND: Patient-held records have been sparsely studied as instruments for
      behavioral change. OBJECTIVE: Our aim was to examine to what extent patients
      report lifestyle changes as a result of using a patient-held health record.
      METHODS: This was a descriptive cross-sectional study based on questionnaires
      distributed in six primary health care centres in Sweden, and comprised 418
      patients aged 20-64 years. The main outcome measure was patients' self-reported
      valuation of having made changes in their health situation as a result of reading
      the booklet regarding their health. RESULTS: Twenty-five percent of the patients
      reported a change in health situation as a result of reading the booklet.
      Exercise, diet and habits related to stress were the most common habits to be
      specified. Age, educational level, health status and smoking habits did not
      influence the proportion of patients who reported lifestyle changes. CONCLUSION:
      The study suggests that patient-held health records might be a useful tool for
      promoting lifestyle changes in primary health care.

PMID- 15465883
TI  - Latrunculin B increases force fluctuation-induced relengthening of ACh
      contracted, isotonically shortened canine tracheal smooth muscle.
AB  - We hypothesized that differences in actin filament length could influence force
      fluctuation-induced relengthening (FFIR) of contracted airway smooth muscle and
      tested this hypothesis as follows. One-hundred micromolar ACh-stimulated canine
      tracheal smooth muscle (TSM) strips set at optimal reference length (Lref) were
      allowed to shorten against 32% maximal isometric force (Fmax) steady preload,
      after which force oscillations of +/-16% Fmax were superimposed. Strips
      relengthened during force oscillations. We measured hysteresivity and calculated
      FFIR as the difference between muscle length before and after 20-min imposed
      force oscillations. Strips were relaxed by ACh removal and treated for 1 h with
      30 nM latrunculin B (sequesters G-actin and promotes depolymerization) or 500 nM
      jasplakinolide (stabilizes actin filaments and opposes depolymerization). A
      second isotonic contraction protocol was then performed; FFIR and hysteresivity
      were again measured. Latrunculin B increased FFIR by 92.2 +/- 27.6% Lref and
      hysteresivity by 31.8 +/- 13.5% vs. pretreatment values. In contrast,
      jasplakinolide had little influence on relengthening by itself; neither FFIR nor
      hysteresivity was significantly affected. However, when jasplakinolide-treated
      tissues were then incubated with latrunculin B in the continued presence of
      jasplakinolide for 1 more h and a third contraction protocol performed,
      latrunculin B no longer substantially enhanced TSM relengthening. In TSM treated
      with latrunculin B + jasplakinolide, FFIR increased by only 3.03 +/- 5.2% Lref
      and hysteresivity by 4.14 +/- 4.9% compared with its first (pre-jasplakinolide or
      latrunculin B) value. These results suggest that actin filament length, in part,
      determines the relengthening of contracted airway smooth muscle.

PMID- 15465884
TI  - Time course of molecular responses of human skeletal muscle to acute bouts of
      resistance exercise.
AB  - Resistance exercise (RE) training, designed to induce hypertrophy, strives for
      optimal activation of anabolic and myogenic mechanisms to increase myofiber size.
      Clearly, activation of these mechanisms must precede skeletal muscle growth. Most
      mechanistic studies of RE have involved analysis of outcome variables after many
      training sessions. This study measured molecular level responses to RE on a scale
      of hours to establish a time course for the activation of myogenic mechanisms.
      Muscle biopsy samples were collected from nine subjects before and after acute
      bouts of RE. The response to a single bout was assessed at 12 and 24 h
      postexercise. Further samples were obtained 24 and 72 h after a second exercise
      bout. RE was induced by neuromuscular electrical stimulation to generate maximal
      isometric contractions in the muscle of interest. A single RE bout resulted in
      increased levels of mRNA for IGF binding protein-4 (84%), MyoD (83%), myogenin
      (approximately 3-fold), cyclin D1 (50%), and p21-Waf1 (16-fold), and a transient
      decrease in IGF-I mRNA (46%). A temporally conserved, significant correlation
      between myogenin and p21 mRNA was observed (r = 0.70, P < or = 0.02). The mRNAs
      for mechano-growth factor, IGF binding protein-5, and the IGF-I receptor were
      unchanged by RE. Total skeletal muscle RNA was increased 72 h after the second
      serial bout of RE. These results indicate that molecular adaptations of skeletal
      muscle to loading respond in a very short time. This approach should provide
      insights on the mechanisms that modulate adaptation to RE and may be useful in
      evaluating RE training protocol variables with high temporal resolution.

PMID- 15465885
TI  - NOS3 deficiency augments hypoxic pulmonary vasoconstriction and enhances systemic
      oxygenation during one-lung ventilation in mice.
AB  - Nitric oxide (NO), synthesized by NO synthases (NOS), plays a pivotal role in
      regulation of pulmonary vascular tone. To examine the role of endothelial NOS
      (NOS3) in hypoxic pulmonary vasoconstriction (HPV), we measured left lung
      pulmonary vascular resistance (LPVR), intrapulmonary shunting, and arterial PO2
      (PaO2) before and during left mainstem bronchus occlusion (LMBO) in mice with and
      without a deletion of the gene encoding NOS3. The increase of LPVR induced by
      LMBO was greater in NOS3-deficient mice than in wild-type mice (151 +/- 39% vs.
      109 +/- 36%, mean +/- SD; P < 0.05). NOS3-deficient mice had a lower
      intrapulmonary shunt fraction than wild-type mice (17.1 +/- 3.6% vs. 21.7 +/-
      2.4%, P < 0.05) during LMBO. Both real-time PaO2 monitoring with an intra
      arterial probe and arterial blood-gas analysis during LMBO showed higher PaO2 in
      NOS3-deficient mice than in wild-type mice (P < 0.05). Inhibition of all three
      NOS isoforms with Nomega-nitro-L-arginine methyl ester (L-NAME) augmented the
      increase of LPVR induced by LMBO in wild-type mice (183 +/- 67% in L-NAME treated
      vs. 109 +/- 36% in saline treated, P < 0.01) but not in NOS3-deficient mice.
      Similarly, systemic oxygenation during one-lung ventilation was augmented by L
      NAME in wild-type mice but not in NOS3-deficient mice. These findings indicate
      that NO derived from NOS3 modulates HPV in vivo and that inhibition of NOS3
      improves systemic oxygenation during acute unilateral lung hypoxia.

PMID- 15465886
TI  - Diminished overload-induced hypertrophy in aged fast-twitch skeletal muscle is
      associated with AMPK hyperphosphorylation.
AB  - Skeletal muscle mass declines with age, as does the potential for overload
      induced fast-twitch skeletal muscle hypertrophy. Because 5'-AMP-activated protein
      kinase (AMPK) activity is thought to inhibit skeletal muscle protein synthesis
      and may therefore modulate muscle mass and hypertrophy, the purpose of this
      investigation was to examine AMPK phosphorylation status (a marker of AMPK
      activity) and its potential association with the attenuated overload-induced
      hypertrophy observed in aged skeletal muscle. One-week overload of fast-twitch
      plantaris and slow-twitch soleus muscles was achieved in young adult (8 mo; n =
      7) and old (30 mo; n = 7) Fischer344 x Brown Norway male rats via unilateral
      gastrocnemius ablation. Significant (P < or = 0.05) age-related atrophy (as
      measured by total protein content) was noted in plantaris and soleus control
      (sham-operated) muscles. In fast-twitch plantaris muscles, percent hypertrophy
      with overload was significantly attenuated with age, whereas AMPK phosphorylation
      status as determined by Western blotting [phospho-AMPK (Thr172)/total AMPK] was
      significantly elevated with age (regardless of loading status). There was also a
      main effect of loading on AMPK phosphorylation status in plantaris muscles
      (overload > control). Moreover, a strong and significant negative correlation (r
      = -0.82) was observed between AMPK phosphorylation status and percent hypertrophy
      in the overloaded plantaris muscles of all animals. In contrast to the plantaris,
      overload-induced hypertrophy of the slow-twitch soleus muscle was similar between
      ages, and AMPK phosphorylation in this muscle was also unaffected by age or
      overload. These data support the possibility that an age-related elevation in
      AMPK phosphorylation may partly contribute to the attenuated hypertrophic
      response observed with age in overloaded fast-twitch plantaris muscle.

PMID- 15465887
TI  - Postexercise hypotension is not explained by a prostaglandin-dependent peripheral
      vasodilation.
AB  - In normally active individuals, postexercise hypotension after a single bout of
      aerobic exercise occurs due to an unexplained peripheral vasodilation.
      Prostaglandin production has been suggested to contribute to the increases in
      blood flow during and after exercise; however, its potential contribution to
      postexercise hypotension has not been assessed. The purpose of this study was to
      determine the potential contribution of a prostaglandin-dependent vasodilation to
      changes in systemic vascular conductance underlying postexercise hypotension;
      this was done by inhibiting production of prostaglandins with the cyclooxygenase
      inhibitor ibuprofen. We studied 11 healthy normotensive men (aged 23.7 +/- 4.2
      yr) before and during the 90 min after a 60-min bout of cycling at 60% peak O(2)
      uptake on a control and a cyclooxygenase inhibition day (randomized). Subjects
      received 10 mg/kg of oral ibuprofen on the cyclooxygenase inhibition day. On both
      study days, arterial blood pressure (automated auscultation) and cardiac output
      (acetylene uptake) were measured, and systemic vascular conductance was
      calculated. Inhibition of cyclooxygenase had no effect on baseline values of mean
      arterial pressure or systemic vascular conductance (P > 0.2). After exercise on
      both days, mean arterial pressure was reduced (-2.2 +/- 1.0 mmHg change with the
      control condition and -3.8 +/- 1.5 mmHg change with the ibuprofen condition, both
      P < 0.05 vs. preexercise) and systemic vascular conductance was increased (5.2 +/
      5.0% change with the control condition and 8.7 +/- 4.1% change with the
      ibuprofen condition, both P < 0.05 vs. preexercise). There were no differences
      between study days (P > 0.6). These data suggest that prostaglandin-dependent
      vasodilation does not contribute to the increased systemic vascular conductance
      underlying postexercise hypotension.

PMID- 15465888
TI  - Effects of disrupted beta1-integrin function on the skeletal response to short
      term hindlimb unloading in mice.
AB  - The study was designed to determine whether beta1-integrin plays a role in
      mediating the acute skeletal response to mechanical unloading. Transgenic (TG)
      mice were generated to express a dominant negative form of beta1-integrin under
      the control of the osteocalcin promoter, which targets expression of the
      transgene to mature osteoblasts. At 63 days of age, wild-type (WT) and TG mice
      were subjected to hindlimb unloading by tail suspension for 1 wk. Pair-fed,
      normally loaded WT and TG mice served as age-matched controls. Bone samples from
      each mouse were processed for quantitative bone histomorphometry and
      biomechanical testing. The skeletal phenotype of TG mice was characterized by
      lower cancellous bone mass in the distal femoral metaphysis (-52%) and lumbar
      vertebral body (-20%), reduced curvature of the proximal tibia (-20%), and
      decreased bone strength (-20%) and stiffness (-23%) of the femoral diaphysis with
      relatively normal indexes of cancellous bone turnover. Hindlimb unloading for
      only 1 wk induced a 10% decline in tibial curvature and a 30% loss of cancellous
      bone in the distal femur due to a combination of increased bone resorption and
      decreased bone formation in both WT and TG mice. However, the strength and
      stiffness of the femoral diaphysis were unaffected by short-term hindlimb
      unloading in both genotypes. The observed increase in osteoclast surface was
      greater in unloaded TG mice (92%) than in unloaded WT mice (52%). Cancellous bone
      formation rate was decreased in unloaded WT (-29%) and TG (-15%) mice, but, in
      contrast to osteoclast surface, the genotype by loading interaction was not
      statistically significant. The results indicate that altered integrin function in
      mature osteoblasts may enhance the osteoclastic response to mechanical unloading
      but that it does not have a major effect on the development of cancellous
      osteopenia in mice during the early stages of hindlimb unloading.

PMID- 15465889
TI  - Mechanics, nonlinearity, and failure strength of lung tissue in a mouse model of
      emphysema: possible role of collagen remodeling.
AB  - Enlargement of the respiratory air spaces is associated with the breakdown and
      reorganization of the connective tissue fiber network during the development of
      pulmonary emphysema. In this study, a mouse (C57BL/6) model of emphysema was
      developed by direct instillation of 1.2 IU of porcine pancreatic elastase (PPE)
      and compared with control mice treated with saline. The PPE treatment caused 95%
      alveolar enlargement (P = 0.001) associated with a 29% lower elastance along the
      quasi-static pressure-volume curves (P < 0.001). Respiratory mechanics were
      measured at several positive end-expiratory pressures in the closed-chest
      condition. The dynamic tissue elastance was 19% lower (P < 0.001), hysteresivity
      was 9% higher (P < 0.05), and harmonic distortion, a measure of collagen-related
      dynamic nonlinearity, was 33% higher in the PPE-treated group (P < 0.001). Whole
      lung hydroxyproline content, which represents the total collagen content, was 48%
      higher (P < 0.01), and alpha-elastin content was 13% lower (P = 0.16) in the PPE
      treated group. There was no significant difference in airway resistance (P =
      0.7). The failure stress at which isolated parenchymal tissues break during
      stretching was 40% lower in the PPE-treated mice (P = 0.002). These findings
      suggest that, after elastolytic injury, abnormal collagen remodeling may play a
      significant role in all aspects of lung functional changes and mechanical forces,
      leading to progressive emphysema.

PMID- 15465890
TI  - Exercise improves impaired ventricular function and alterations of cardiac
      myofibrillar proteins in diabetic dyslipidemic pigs.
AB  - Chronic diabetes is often associated with cardiomyopathy, which may result, in
      part, from defects in cardiac muscle proteins. We investigated whether a 20-wk
      porcine model of diabetic dyslipidemia (DD) would impair in vivo myocardial
      function and yield alterations in cardiac myofibrillar proteins and whether
      endurance exercise training would improve these changes. Myocardial function was
      depressed in anesthetized DD pigs (n = 12) compared with sedentary controls (C; n
      = 13) as evidenced by an approximately 30% decrease in left ventricular
      fractional shortening and an approximately 35% decrease in +dP/dt measured by
      noninvasive echocardiography and direct cardiac catheterization, respectively.
      This depression in myocardial function was improved with chronic exercise as
      treadmill-trained DD pigs (DDX) (n = 13) had significantly greater fractional
      shortening and +dP/dt than DD animals. Interestingly, the isoform expression
      pattern of the myofibrillar regulatory protein, cardiac troponin T (cTnT), was
      significantly shifted from cTnT1 toward cTnT2 and cTnT3 in DD pigs. Furthermore,
      this change in cTnT isoform expression pattern was prevented in DDX pigs.
      Finally, there was a decrease in baseline levels of cAMP-dependent protein kinase
      induced phosphorylation of the myofibrillar proteins troponin I and myosin
      binding protein-C in DD animals. Overall, these results indicate that 20 wk of DD
      lead to myocardial dysfunction coincident with significant alterations in
      myofibrillar proteins, both of which are prevented with endurance exercise
      training, implying that changes in myofibrillar proteins may contribute, at least
      in part, to cardiac dysfunction associated with diabetic cardiomyopathy.

PMID- 15465891
TI  - The involvement of hydroxyl radical and cyclooxygenase metabolites in the
      activation of lung vagal sensory receptors by circulatory endotoxin in rats.
AB  - Circulatory endotoxin can stimulate vagal pulmonary C fibers and rapidly adapting
      receptors (RARs) in rats, but the underlying mechanisms are not clear. We
      investigated the involvement of hydroxyl radicals and cyclooxygenase metabolites
      in the stimulation of C fibers and RARs by circulatory endotoxin (50 mg/kg) in
      112 anesthetized, paralyzed, and artificially ventilated rats. In rats pretreated
      with the vehicle, endotoxin stimulated C fibers and RARs and caused a slight
      increase in total lung resistance (Rl) and a decrease in dynamic lung compliance.
      In rats pretreated with dimethylthiourea (a hydroxyl radical scavenger) alone,
      indomethacin (a cyclooxygenase inhibitor) alone, or a combination of the two, C
      fiber and RAR responses [C fiber: change (Delta) = -62, -79, and -85%; RAR: Delta
      = -80, -84, and -84%, respectively] were reduced, and the Rl response was
      prevented. The suppressive effects of a combination of dimethylthiourea and
      indomethacin on the C-fiber and RAR responses were not superior to indomethacin
      alone. In rats pretreated with isoproterenol (a bronchodilator), the C-fiber
      response was not significantly affected (Delta = -26%), the RAR response was
      reduced (Delta = -88%), and the Rl response was prevented. None of these
      pretreatments affected the dynamic lung compliance response. These results
      suggest that 1) both hydroxyl radicals and cyclooxygenase metabolites are
      involved in the endotoxin-induced stimulation of C fibers and RARs, and 2) the
      involvement of these two metabolites in the C-fiber stimulation may be due to
      their chemical effects, whereas that in the RAR stimulation may be due to their
      bronchoconstrictive effects.

PMID- 15465892
TI  - Impact of postnatal glucocorticoids on early lung development.
AB  - Inhaled glucocorticoid treatment during the first 2 yr of life is controversial
      because this is a period of major structural remodeling of the lung. Rabbits
      received aerosolized budesonide (Bud; 250 microg/ml) or injected dexamethasone
      (Dex; 0.05 mg.ml(-1).kg(-1)) between 1 and 5 wk of age. Treatment with Bud caused
      specific growth retardation of the lung. Dex but not Bud affected the mechanical
      properties of the lung parenchyma, when corrected for lung volume. Small
      peripheral airway walls in both glucocorticoid groups were thinner and had fewer
      alveolar attachment points with greater distance between attachments than
      controls, but collagen content was not affected by glucocorticoids. Dex led to
      reduced body weight, lung volume, alveolar number, and surface area. The alveolar
      size and number and elastin content, when related to lung volume, was not
      affected by Bud, suggesting normal structural development but inhibition of total
      growth. Arterial wall thickness and diameter were affected by Bud. This study
      demonstrates that developing lungs are sensitive to inhaled glucocorticoids. As
      such, the use of glucocorticoids in young infants and children should be
      monitored with caution and only the lowest doses that yield significant clinical
      improvement should be used.

PMID- 15465893
TI  - p38 MAP kinase inhibitor reverses stress-induced cardiac myocyte dysfunction.
AB  - Stress is gaining increasing acceptance as an independent risk factor
      contributing to adverse cardiovascular outcomes. Potential mechanisms responsible
      for the deleterious effects of stress on the development and progression of
      cardiovascular disease remain to be elucidated. An established animal model of
      stress in humans is the prenatally stressed (PS) rat. We stressed rats in their
      third trimester of pregnancy by daily injections of saline and moving from cage
      to cage. Male offspring of these stressed dams (PS) and age-matched male control
      offspring (control) were further subjected to restraint stress (R) at 6 and 7 wk
      of age. Echocardiography revealed a significant decrease in fractional shortening
      in PS + R vs. controls + R (45.8 +/- 3.9 vs. 61.9 +/- 2.4%, PS + R vs. controls +
      R; P < 0.01; n = 12). Isolated adult rat ventricular myocytes from PS + R also
      revealed diminished fractional shortening (6.7 +/- 0.8 vs. 12.7 +/- 1.1%, PS + R
      vs. controls + R; P < 0.01; n = 24) and blunted inotropic responses to
      isoproterenol (P < 0.01; n = 24) determined by automated border detection. The
      p38 mitogen-activated protein (MAP) kinase inhibitor SB-203580 blocked p38 MAP
      kinase phosphorylation, reversed the depression in fractional shortening, and
      partially ameliorated the blunted adrenergic signaling seen in adult rat
      ventricular myocytes from PS + R. Phosphorylation of p38 MAP kinase in cardiac
      myocytes by stress may be sufficient to lead to myocardial dysfunction in animal
      models and possibly humans.

PMID- 15465895
TI  - A family of ordered logistic regression models fit by data expansion.

PMID- 15465896
TI  - In search of the best available version of the truth.

PMID- 15465898
TI  - Earthquake and suicide: bringing context back into disaster epidemiological
      studies.

PMID- 15465899
TI  - Commentary: The pitfalls of policy history. Writing the past to change the
      present.

PMID- 15465900
TI  - Commentary: History in the search of policy.

PMID- 15465901
TI  - Commentary: Medicine, population, and tuberculosis.

PMID- 15465902
TI  - Medical issues in historical demography.

PMID- 15465903
TI  - Misleading quotations and other errors persist in rejoinder on breast cancer
      screening.

PMID- 15465904
TI  - Contemporary patterns of Pacific Island mortality.
AB  - BACKGROUND: The Pacific Island countries are at different stages of the
      demographic and epidemiological transitions. The availability of accurate and
      current mortality data is of vital importance for priority setting in health.
      Available mortality data generally underestimate death rates among both children
      and adults. In many Pacific Island populations, little is reliably known about
      levels and causes of death, particularly among adults. METHODS: The results of
      two comprehensive approaches to obtaining mortality estimates are reported.
      First, a systematic review of available life expectancy and infant mortality
      information reported by countries from 1990 onwards was undertaken and evaluated
      with respect to quality, and a final "best estimate" was established. Methods
      were based on registered deaths and indirect demographic methods. The second
      approach consisted of a demographic evaluation of vital registration data for
      completeness, with death rates adjusted accordingly, or where vital registration
      was not available, the application of new model life table methods to generate
      life tables from estimates of child mortality, as used by the World Health
      Organisation (WHO). RESULTS: This analysis reveals substantial uncertainty about
      mortality conditions in Pacific Island populations. In some countries, life
      expectancy variations of 10 years or more were recorded in the 1990s, depending
      on the source. Best approaches suggest that life expectancy (at birth) varied
      considerably, from levels of around 55-60 years in some Melanesian and
      Micronesian states to levels above 70 years in low-mortality countries. The
      principal issues with regard to uncertainty around mortality levels include
      underenumerated vital registration data; annual stochastic fluctuations in
      mortality in small populations; errors in the imputation of adult mortality from
      infant and childhood rates; implausible results from indirect demographic
      methods; use of possibly inappropriate model life tables to adjust death data or
      for indirect methods; and inadequately described and implausible projections. The
      WHO model life table method based on adjusted vital registration generally
      yielded results similar to those suggested by an evaluation of published data,
      with some exceptions, which are further discussed. CONCLUSIONS: This study
      indicates the urgent need to improve infrastructure, training, and resources for
      routine mortality estimation in many Pacific Island countries in order to better
      inform and evaluate health and public policy.

PMID- 15465905
TI  - Commentary: The McKeown debate: time for burial.

PMID- 15465907
TI  - Inequity, acculturation and the 'Mediterranean paradox'.

PMID- 15465908
TI  - Cup is a nucleocytoplasmic shuttling protein that interacts with the eukaryotic
      translation initiation factor 4E to modulate Drosophila ovary development.
AB  - In Drosophila, the product of the fs (2)cup gene (Cup) is known to be crucial for
      diverse aspects of female germ-line development. Its functions at the molecular
      level, however, have remained mainly unexplored. Cup was found to directly
      associate with eukaryotic translation initiation factor 4E (eIF4E). In this
      report, we show that Cup is a nucleocytoplasmic shuttling protein and that the
      interaction with eIF4E promotes retention of the Cup protein in the cytoplasm.
      Cup is required for the correct accumulation and localization of eIF4E within the
      posterior cytoplasm of developing oocytes. We furthermore show that cup and eIF4E
      interact genetically, because a reduction in the level of eIF4E activity
      deteriorates the development and growth of ovaries bearing homozygous cup mutant
      alleles. Our results reveal a crucial role for the Cup-eIF4E complex in ovary
      specific developmental programs.

PMID- 15465909
TI  - Ion motions in molecular dynamics simulations on DNA.
AB  - Counterions play a significant role in DNA structure and function, and molecular
      dynamics (MD) simulations offer the prospect of detailed description of the
      dynamical structure of ions at the molecular level. However, the motions of
      mobile counterions are notably slow to converge in MD on DNA. Obtaining accurate
      and reliable MD simulations requires knowing just how much sampling is required
      for convergence of each of the properties of interest. To address this issue, MD
      on a d(CGCGAATTCGCG) duplex in a dilute aqueous solution of water and 22 Na+
      counterions was performed until convergence was achieved. The calculated first
      shell ion occupancies and DNA-Na+ radial distribution functions were computed as
      a function of time to assess convergence, and compared with relaxation times of
      the DNA internal parameters shift, slide, rise, tilt, roll, and twist. The
      sequence dependence of fractional occupancies of ions in the major and minor
      grooves of the DNA is examined, and the possibility of correlation between ion
      proximity and DNA minor groove widths is investigated.

PMID- 15465910
TI  - Effects of the U1C L13 mutation and temperature regulation of yeast commitment
      complex formation.
AB  - The U1 small nuclear ribonucleoprotein particle U1C protein has a zinc finger
      like structure (C2H2 motif) at its N terminus, which is conserved from yeast to
      humans. Mutations of amino acid L13 within this domain rescue the essential
      function of the helicase protein Prp28p. Prp28p has been implicated in unwinding
      the 5' splice site (5'ss)-U1 small nuclear RNA (snRNA) base-pairing, to allow
      replacement of U1 snRNA with U6 snRNA during spliceosome assembly. The L13
      phenotype has therefore been interpreted to indicate that WT U1C contributes to
      5'ss-U1 snRNA stabilization by binding to the RNA duplex. We show here that an
      L13 mutant extract cannot form stable base-pairing at room temperature but is
      permissive for U1-5'ss base-pairing at low temperature. This phenotype is similar
      to that of a U1C-depleted extract, indicating that the U1C L13 mutation is a
      strong loss-of-function mutation. The two mutant extracts are unlike a WT
      extract, which undergoes stable pairing at room temperature but little or no
      pairing at low temperature. Taken together with previous results and the failure
      to observe a direct interaction of U1C with the U1-5'ss duplex, the data suggest
      that U1C contributes indirectly to stable U1-5'ss base-pairing under permissive
      conditions. A model is proposed to account for the L13 results.

PMID- 15465911
TI  - Double-knockout mice for alpha- and beta-synucleins: effect on synaptic
      functions.
AB  - An abundant presynaptic protein, alpha-synuclein, is centrally involved in the
      pathogenesis of Parkinson's disease. However, conflicting data exist about the
      normal function of alpha-synuclein, possibly because alpha-synuclein is redundant
      with the very similar beta-synuclein. To investigate the functions of synucleins
      systematically, we have now generated single- and double-knockout (KO) mice that
      lack alpha- and/or beta-synuclein. We find that deletion of synucleins in mice
      does not impair basic brain functions or survival. We detected no significant
      changes in the ultrastructure of synuclein-deficient synapses, in short- or long
      term synaptic plasticity, or in the pool size or replenishment of recycling
      synaptic vesicles. However, protein quantitations revealed that KO of synucleins
      caused selective changes in two small synaptic signaling proteins, complexins and
      14-3-3 proteins. Moreover, we found that dopamine levels in the brains of double
      KO but not single-KO mice were decreased by approximately 20%. In contrast,
      serotonin levels were unchanged, and dopamine uptake and release from isolated
      nerve terminals were normal. These results show that synucleins are not essential
      components of the basic machinery for neurotransmitter release but may contribute
      to the long-term regulation and/or maintenance of presynaptic function.

PMID- 15465912
TI  - Reverse transcriptase and endonuclease activities encoded by Penelope-like
      retroelements.
AB  - Penelope-like elements are a class of retroelement that have now been identified
      in >50 species belonging to at least 10 animal phyla. The Penelope element
      isolated from Drosophila virilis is the only transpositionally active
      representative of this class isolated so far. The single ORF of Penelope and its
      relatives contains regions homologous to a reverse transcriptase of atypical
      structure and to the GIY-YIG, or Uri, an endonuclease (EN) domain not previously
      found in retroelements. We have expressed the single ORF of Penelope in a
      baculovirus expression system and have shown that it encodes a polyprotein with
      reverse transcriptase activity that requires divalent cations (Mn2+ and Mg2+). We
      have also expressed and purified the EN domain in Escherichia coli and have
      demonstrated that it has EN activity in vitro. Mutations in the conserved
      residues of the EN catalytic module abolish its nicking activity, whereas the DNA
      binding properties of the mutant proteins remain unaffected. Only one strand of
      the target sequence is cleaved, and there is a certain degree of cleavage
      specificity. We propose that the Penelope EN cleaves the target DNA during
      transposition, generating a primer for reverse transcription. Our results show
      that an active Uri EN has been adopted by a retrotransposon.

PMID- 15465913
TI  - Paracellular Cl- permeability is regulated by WNK4 kinase: insight into normal
      physiology and hypertension.
AB  - Paracellular ion flux across epithelia occurs through selective and regulated
      pores in tight junctions; this process is poorly understood. Mutations in the
      kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a disease featuring
      hypertension and hyperkalemia. Whereas WNK4 is known to regulate several
      transcellular transporters and channels involved in NaCl and K+ homeostasis, its
      localization to tight junctions suggests it might also regulate paracellular
      flux. We performed electrophysiology on mammalian kidney epithelia with inducible
      expression of various WNK4 constructs. Induction of wild-type WNK4 reduced
      transepithelial resistance by increasing absolute chloride permeability. PHAII
      mutant WNK4 produced markedly larger effects, whereas kinase-mutant WNK4 had no
      effect. The electrochemical and pharmacologic properties of these effects
      indicate they are attributable to the paracellular pathway. The effects of WNK4
      persist when induction is delayed until after tight-junction formation,
      demonstrating a dynamic effect. WNK4 did not alter the flux of uncharged solutes,
      or the expression or localization of selected tight-junction proteins.
      Transmission and freeze-fracture electron microscopy showed no effect of WNK4 on
      tight-junction structure. These findings implicate WNK signaling in the
      coordination of transcellular and paracellular flux to achieve NaCl and K+
      homeostasis, explain PHAII pathophysiology, and suggest that modifiers of WNK
      signaling may be potent antihypertensive agents.

PMID- 15465914
TI  - Activation of naive CD4 T cells by anti-CD3 reveals an important role for Fyn in
      Lck-mediated signaling.
AB  - Although there was no impairment in IL-2 secretion and proliferation of Fyn
      deficient naive CD4 cells after stimulation with antigen and antigen-presenting
      cells, stimulation of these cells with anti-CD3 and anti-CD28 revealed profound
      defects. Crosslinking of purified wild-type naive CD4 cells with anti-CD3
      activated Lck and initiated the signaling cascade downstream of Lck, including
      phosphorylation of ZAP-70, LAT, and PLC-gamma1; calcium flux; and
      dephosphorylation and nuclear translocation of the nuclear factor of activated T
      cells (NFAT)p. All of these signaling events were diminished severely in Fyn
      deficient naive cells activated by CD3 crosslinking. Coaggregation of CD3 and CD4
      reconstituted this Lck-dependent signaling pathway in Fyn(-/-) T cells. These
      results suggest that when signaling of naive T cells is restricted to the T cell
      antigen receptor, Fyn plays an essential role by positive regulation of Lck
      activity.

PMID- 15465916
TI  - Phosphatidylinositol (4,5) bisphosphate regulates HIV-1 Gag targeting to the
      plasma membrane.
AB  - A critical early event in the HIV type 1 (HIV-1) particle assembly pathway is the
      targeting of the Gag protein to the site of virus assembly. In many cell types,
      assembly takes place predominantly at the plasma membrane. Cellular factors that
      regulate Gag targeting remain undefined. The phosphoinositide
      phosphatidylinositol (4,5) bisphosphate [PI(4,5)P2] controls the plasma membrane
      localization of a number of cellular proteins. To explore the possibility that
      this lipid may be involved in Gag targeting and virus particle production, we
      overexpressed phosphoinositide 5-phosphatase IV, an enzyme that depletes cellular
      PI(4,5)P2, or overexpressed a constitutively active form of Arf6 (Arf6/Q67L),
      which induces the formation of PI(4,5)P2-enriched endosomal structures. Both
      approaches severely reduced virus production. Upon 5-phosphatase IV
      overexpression, Gag was no longer localized on the plasma membrane but instead
      was retargeted to late endosomes. Strikingly, in cells expressing Arf6/Q67L, Gag
      was redirected to the PI(4,5)P2-enriched vesicles and HIV-1 virions budded into
      these vesicles. These results demonstrate that PI(4,5)P2 plays a key role in Gag
      targeting to the plasma membrane and thus serves as a cellular determinant of HIV
      1 particle production.

PMID- 15465915
TI  - Ten species in one: DNA barcoding reveals cryptic species in the neotropical
      skipper butterfly Astraptes fulgerator.
AB  - Astraptes fulgerator, first described in 1775, is a common and widely distributed
      neotropical skipper butterfly (Lepidoptera: Hesperiidae). We combine 25 years of
      natural history observations in northwestern Costa Rica with morphological study
      and DNA barcoding of museum specimens to show that A. fulgerator is a complex of
      at least 10 species in this region. Largely sympatric, these taxa have mostly
      different caterpillar food plants, mostly distinctive caterpillars, and somewhat
      different ecosystem preferences but only subtly differing adults with no
      genitalic divergence. Our results add to the evidence that cryptic species are
      prevalent in tropical regions, a critical issue in efforts to document global
      species richness. They also illustrate the value of DNA barcoding, especially
      when coupled with traditional taxonomic tools, in disclosing hidden diversity.

PMID- 15465917
TI  - Aqueous urea solution destabilizes Abeta(16-22) oligomers.
AB  - We use long multiple trajectories generated by molecular dynamics simulations to
      probe the stability of oligomers of Abeta(16-22) (KLVFFAE) peptides in aqueous
      urea solution. High concentration of urea promotes the formation of beta-strand
      structures in Abeta(16-22) monomers, whereas in water they adopt largely compact
      random coil structures. The tripeptide system, which forms stable antiparallel
      beta-sheet structure in water, is destabilized in urea solution. The enhancement
      of beta-strand content in the monomers and the disruption of oligomeric structure
      occur largely by direct interaction of urea with the peptide backbone. Our
      simulations suggest that the oligomer unbinding dynamics is determined by two
      opposing effects, namely, by the increased propensity of monomers to form beta
      strands and the rapid disruption of the oligomers. The qualitative conclusions
      are affirmed by using two urea models. Because the proposed destabilization
      mechanism depends largely on hydrogen bond formation between urea and the peptide
      backbone, we predict that high urea concentration will destabilize oligomers of
      other amyloidogenic peptides as well.

PMID- 15465918
TI  - Conditional mutagenesis using site-specific recombination in Plasmodium berghei.
AB  - Reverse genetics in Plasmodium, the genus of parasites that cause malaria, still
      faces major limitations. Only red blood cell stages of this haploid parasite can
      be transfected. Consequently, the function of many essential genes in these and
      subsequent stages, including those encoding vaccine candidates, cannot be
      addressed genetically. Here, we establish conditional mutagenesis in Plasmodium
      by using site-specific recombination and the Flp/FRT system of yeast. Site
      specific recombination is induced after cross-fertilization in the mosquito
      vector of two clones containing either the target sequence flanked by two FRT
      sites or the Flp recombinase. Parasites that have undergone recombination are
      recognized in the cross progeny through the expression of a fluorescence marker.
      This approach should permit to dissect the function of any essential gene of
      Plasmodium during the haploid phase of its life, i.e., during infection of
      salivary glands in the mosquito and infection of both the liver and red blood
      cells in the mammal.

PMID- 15465919
TI  - Using fluorescent sensors to detect botulinum neurotoxin activity in vitro and in
      living cells.
AB  - Botulinum neurotoxins (BoNTs) act as zinc-dependent endopeptidases that cleave
      proteins required for neurotransmitter release. To detect toxin activity,
      fragments of the toxin substrate proteins, synaptobrevin (Syb) or synaptosome
      associated protein of 25 kDa (SNAP-25), were used to link cyan fluorescent
      protein (CFP) to yellow fluorescent protein (YFP). Cleavage of these fusion
      proteins by BoNTs abolished fluorescence resonance energy transfer between the
      CFP and YFP, providing a sensitive means to detect toxin activity in real-time in
      vitro. Furthermore, using full-length SNAP-25 and Syb as the linkers, we report
      two fluorescent biosensors that can detect toxin activity within living cells.
      Cleavage of the SNAP-25 fusion protein abolished fluorescence resonance energy
      transfer between CFP and YFP, and cleavage of Syb resulted in spatial
      redistribution of YFP fluorescence in cells. This approach provides a means to
      carry out cell-based screening of toxin inhibitors and to study toxin activity in
      situ. By using these biosensors, we found that the subcellular localizations of
      SNAP-25 and Syb are critical for efficient cleavage by BoNT/A and B,
      respectively.

PMID- 15465920
TI  - Interaction between the GAGA factor and Mod(mdg4) proteins promotes insulator
      bypass in Drosophila.
AB  - Chromatin insulators or boundaries are proposed to structure the chromatin fiber
      into functionally independent domains by promoting the formation of chromatin
      loops. These elements can block the communication between an enhancer and a gene
      when placed between them. Interestingly, it has been previously observed that two
      tandem copies of the Drosophila Su(Hw) insulator abolish this enhancer-blocking
      activity, presumably through pairing. This bypass effect has not been described
      with other insulators, however. In this report, we show that the insertion of
      binding sites for the GAGA factor (GAF) between an enhancer and the Su(Hw)
      insulator allows bypassing of the insulator. This bypass relies on the activity
      of both the GAF protein and the Mod(mdg4)-67.2 protein, a factor required for
      Su(Hw) insulator activity. We show that these two proteins interact in vitro and
      in vivo, providing molecular evidence of pairing between the GAF sites and the
      Su(Hw) insulator. Finally, we show that placing the Mcp boundary together with
      the Su(Hw) insulator between an enhancer and a promoter leads to bypass, again in
      a GAF- and Mod(mdg4)-dependent manner. Our data provide direct evidence that
      heterologous insulators can be bypassed by distal enhancers and identify the
      interaction between GAF and Mod(mdg4) as a possible means to regulate insulator
      activity.

PMID- 15465921
TI  - Gene transfer of cocaine hydrolase suppresses cardiovascular responses to cocaine
      in rats.
AB  - We previously found that injection of a cocaine hydrolase (CocE) engineered from
      human butyrylcholinesterase will transiently accelerate cocaine metabolism in
      rats while reducing physiological and behavioral responses. To investigate more
      extended therapeutic effects, CocE cDNA was incorporated into a replication
      incompetent type-5 adenoviral vector with a cytomegalovirus promoter. In rats
      dosed with this agent (2.2 x 10(9) plaque-forming units), the time course of
      expression was characterized by reverse transcription polymerase chain reaction
      for CocE mRNA and by radiometric assay for enzyme activity. Liver and plasma
      showed comparable expression, beginning 2 days after vector administration and
      peaking between 5 and 7 days. Plasma CocE content was up to 100 mU/ml, with total
      cocaine hydrolyzing activity 3000-fold greater than in "empty vector" or
      untreated controls. This level of expression approximated that found immediately
      after i.v. injection of purified hydrolase, 3 mg/kg, a dose that shortened
      cocaine halflife and blunted cardiovascular effects. Sucrose density gradient
      analysis showed that 96% of the circulating CocE activity was associated with
      tetrameric enzyme forms, expected to be stable in vivo. Consistent with this
      expectation, CocE from vector-treated rats showed a plasma t(1/2) of 33 h when
      reinjected into naive rats. Transduction of another mutant butyrylcholinesterase,
      Applied Molecular Evolution mutant 359 (AME(359)), caused plasma cocaine
      hydrolase activity to rise 50,000-fold. At the point of peak AME(359) expression,
      cocaine was cleared from the blood too rapidly for accurate measurement, and
      pressor responses to the injection of drug were greatly impaired.

PMID- 15465922
TI  - The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates
      the anti-inflammatory actions of palmitoylethanolamide.
AB  - Palmitoylethanolamide (PEA), the naturally occurring amide of palmitic acid and
      ethanolamine, reduces pain and inflammation through an as-yet-uncharacterized
      mechanism. Here, we identify the nuclear receptor peroxisome proliferator
      activated receptor-alpha (PPAR-alpha) as the molecular target responsible for the
      anti-inflammatory properties of PEA. PEA selectively activates PPAR-alpha in
      vitro with an EC(50) value of 3.1 +/- 0.4 microM and induces the expression of
      PPAR-alpha mRNA when applied topically to mouse skin. In two animal models,
      carrageenan-induced paw edema and phorbol ester-induced ear edema, PEA attenuates
      inflammation in wild-type mice but has no effect in mice deficient in PPAR-alpha.
      The natural PPAR-alpha agonist oleoylethanolamide (OEA) and the synthetic PPAR
      alpha agonists GW7647 and Wy-14643 mimic these effects in a PPAR-alpha-dependent
      manner. These findings indicate that PPAR-alpha mediates the anti-inflammatory
      effects of PEA and suggest that this fatty-acid ethanolamide may serve, like its
      analog OEA, as an endogenous ligand of PPAR-alpha.

PMID- 15465923
TI  - H3 autoreceptors modulate histamine synthesis through calcium/calmodulin- and
      cAMP-dependent protein kinase pathways.
AB  - H(3) autoreceptors provide feedback control of neurotransmitter synthesis in
      histaminergic neurons, but the transduction pathways involved are poorly
      understood. In rat brain cortical slices, histamine synthesis can be stimulated
      by depolarization and inhibited by H(3) agonists. We show that histamine
      synthesis stimulation by depolarization with 30 mM K(+) requires extracellular
      calcium entry, mostly through N-type channels, and subsequent activation of
      calcium/calmodulin-dependent protein kinase type II. In vitro, this kinase
      phosphorylated and activated histidine decarboxylase, the histamine-synthesizing
      enzyme. Inhibition of depolarization-stimulated histamine synthesis by the
      histamine H(3) receptor agonist imetit was impaired by preincubation with
      pertussis toxin and by the presence of a myristoylated peptide (myristoyl-N
      QEHAQEPERQYMHIGTMVE-FAYALVGK) blocking the actions of G-protein betagamma
      subunits. The stimulation of another G(i/o)-coupled receptor, adenosine A(1),
      also decreased depolarization-stimulated histamine synthesis. In contrast,
      protein kinase A activation, which is also repressed by H(3) receptors, elicited
      a depolarization- and calcium/calmodulin-independent stimulation of histamine
      synthesis. Protein kinase A was able also to phosphorylate and activate histidine
      decarboxylase in vitro. These results show how depolarization activates histamine
      synthesis in nerve endings and demonstrate that both pathways modulating
      neurotransmitter synthesis are controlled by H(3) autoreceptors.

PMID- 15465924
TI  - Antitumor activity of methoxymorpholinyl doxorubicin: potentiation by cytochrome
      P450 3A metabolism.
AB  - Methoxymorpholinyl doxorubicin (MMDX) is a novel liver cytochrome P450 (P450)
      activated anticancer prodrug whose toxicity toward cultured tumor cells can be
      potentiated up to 100-fold by incubation with liver microsomes and NADPH. In the
      present study, a panel of human liver microsomes activated MMDX with potentiation
      ratios directly correlated to the CYP3A-dependent testosterone 6beta-hydroxylase
      activity of each liver sample. Microsome-activated MMDX exhibited nanomolar
      IC(50) values in growth-inhibition assays of human tumor cell lines representing
      multiple tissues of origin: lung (A549 cells), brain (U251 cells), colon (LS180
      cells), and breast (MCF-7 cells). Analysis of individual cDNA-expressed CYP3A
      enzymes revealed that rat CYP3A1 and human CYP3A4 activated MMDX more efficiently
      than rat CYP3A2 and that human P450s 3A5 and 3A7 displayed little or no activity.
      MMDX cytotoxicity was substantially increased in Chinese hamster ovary cells
      after stable expression of CYP3A4 in combination with P450 reductase. CYP3A
      activation of MMDX abolished the parent drug's residual cross-resistance in a
      doxorubicin-resistant MCF-7 cell line that overexpresses P-glycoprotein. CYP3A
      activated MMDX displayed a comparatively high intrinsic stability, with a t(1/2)
      of approximately 5.5 h at 37 degrees C. MMDX was rapidly activated by CYP3A at
      low ( approximately 1-5 nM) prodrug concentrations, with 100% tumor cell kill
      obtained after as short as a 2-h exposure to the activated metabolite. These
      findings demonstrate that MMDX can be activated by CYP3A metabolism to a potent,
      long-lived, and cell-permeable cytotoxic metabolite and suggest that this
      anthracycline prodrug may be used in combination with CYP3A4 in a P450 prodrug
      activation-based gene therapy for cancer treatment.

PMID- 15465925
TI  - Relaxin-3/insulin-like peptide 5 chimeric peptide, a selective ligand for G
      protein-coupled receptor (GPCR)135 and GPCR142 over leucine-rich repeat
      containing G protein-coupled receptor 7.
AB  - Relaxin-3, the most recently identified member of relaxin/insulin family, is an
      agonist for leucine-rich repeat-containing G protein-coupled receptor (LGR)7,
      GPCR135, and GPCR142. LGR7 can be pharmacologically differentiated from GPCR135
      and GPCR142 by its high affinity for relaxin. Selective ligands that specifically
      activate GPCR135 or GPCR142 are highly desirable for studying their functional
      roles. We have created chimeric peptides that consist of the B-chain of human
      relaxin-3 in combination with various A-chains from other members of the
      relaxin/insulin family. Pharmacological characterization of these chimeric
      peptides indicates the A-chain from relaxin-1, relaxin-2, insulin-like peptide
      (INSL)3, and INSL6 does not change the pharmacological properties of relaxin-3
      significantly. In contrast, substitution of the relaxin-3 A-chain with the A
      chain from INSL5 results in a chimeric peptide that selectively activates GPCR135
      and GPCR142 over LGR7. This study demonstrates that the A-chains among some of
      the insulin/relaxin family members are pharmacologically exchangeable. The
      relaxin-3/INSL5 chimeric peptide is a potential tool to study in vivo function of
      GPCR135. In addition, because of the substitution of a very hydrophobic peptide
      (the A-chain of relaxin-3) with a very hydrophilic peptide (the A-chain from
      INSL5), the radiolabeled (125)I-relaxin-3/INSL5 chimera is a suitable ligand
      (high-affinity, low-nonspecific binding) for receptor autoradiographic studies on
      tissue sections.

PMID- 15465927
TI  - Dynamics of Ca2+-dependent Cl- channel modulation by niflumic acid in rabbit
      coronary arterial myocytes.
AB  - Calcium-activated chloride channels (Cl(Ca)) are crucial regulators of vascular
      tone by promoting a depolarizing influence on the resting membrane potential of
      vascular smooth muscle cells. Niflumic acid (NFA), a potent blocker of Cl(Ca) in
      vascular myocytes, was shown recently to cause inhibition and paradoxical
      stimulation of sustained calcium-activated chloride currents [I(Cl(Ca))] in
      rabbit pulmonary artery myocytes. The aims of the present study were to
      investigate whether NFA produced a similar dual effect in coronary artery smooth
      muscle cells and to determine the concentration-dependence and dynamics of such a
      phenomenon. Sustained I(Cl(Ca)) evoked by intracellular Ca(2+) clamped at 500 nM
      were dose-dependently inhibited by NFA (IC(50) = 159 microM) and transiently
      augmented in a concentration-independent manner (10 microM to 1 mM) approximately
      2-fold after NFA removal. However, the time to peak and duration of NFA-enhanced
      I(Cl(Ca)) increased in a concentration-dependent fashion. Moreover, the rate of
      recovery was reduced by membrane depolarization, suggesting the involvement of a
      voltage-dependent step in the interaction of NFA, leading to stimulation of
      I(Cl(Ca)). Computer simulations derived from a kinetic model involving low (K(i)
      = 1.25 mM) and high (K(i) < 30 microM) affinity sites could reproduce the
      properties of the NFA-modulated I(Cl(Ca)) fairly well.

PMID- 15465926
TI  - Alternative promoters determine tissue-specific expression profiles of the human
      microsomal epoxide hydrolase gene (EPHX1).
AB  - Microsomal epoxide hydrolase (EPHX1) catalyzes hydration reactions that determine
      the cellular disposition of reactive epoxide derivatives. Whereas the previously
      defined EPHX1 exon 1 sequence (E1) is derived from a promoter proximal to exon 2
      of the EPHX1 coding region, in this investigation, we identified an alternative
      EPHX1 exon 1 sequence, E1-b, originating from a gene promoter localized
      approximately 18.5 kb upstream of exon 2. Northern hybridizations demonstrated
      that the E1-b variant is widely expressed and that the E1-b promoter functions as
      the primary driver of EPHX1 expression in human tissues. In contrast, the E1
      promoter directs expression only in the liver. To examine the basis for liver
      specific usage of the E1 promoter, we identified several potential cis-regulatory
      elements that included GATA (-110/-105) and hepatocyte nuclear factor 3 (HNF3) (
      96/-88) motifs. GATA-4 was the principal GATA family member interacting with its
      respective motif, whereas both HNF3alpha and HNF3beta were capable of interacting
      with the HNF3 element. GATA-4 and HNF3alpha/HNF3beta DNA binding complexes were
      enriched in hepatic cells. Site-directed mutagenesis and transactivation analyses
      of the E1 promoter revealed that GATA-4 is probably a principal factor that
      regulates liver-specific expression of the E1 variant, with HNF3alpha and
      HNF3beta acting to negatively regulate GATA-4 function in hepatic cells.

PMID- 15465928
TI  - The protein kinase C inhibitor Go6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13
      methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole] potentiates agonist
      induced mitogen-activated protein kinase activation through tyrosine
      phosphorylation of the epidermal growth factor receptor.
AB  - Protein kinase C (PKC) isoforms are important transducers of signals from G
      protein-coupled receptors (GPCRs) to diverse cellular targets, including
      extracellular signal-regulated kinases 1 and 2 (ERK1/2). Clone 9 rat hepatocytes
      (C9 cells) express receptors for angiotensin II (Ang II) type 1, lysophosphatidic
      acid (LPA), and epidermal growth factor (EGF), and their stimulation causes
      transient ERK1/2 phosphorylation through transactivation of the epidermal growth
      factor receptor (EGF-R). Inhibition of PKC by Go6983 [2-[1-(3
      dimethylaminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl)maleimide], or PKC
      depletion by prolonged phorbol 12-myristate 13-acetate (PMA) treatment,
      attenuated ERK1/2 activation by Ang II and PMA, but not by LPA and EGF. In
      contrast, another PKC inhibitor, Go6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro
      13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole], enhanced basal and
      agonist-stimulated phosphorylation of ERK1/2, which was not caused by alteration
      in receptor binding and internalization, stimulation of inositol phosphate
      production, or activation of Pyk2 and Src tyrosine kinases. However, Go6976
      enhanced agonist-induced tyrosine phosphorylation of the EGF receptor, possibly
      through inhibition of protein tyrosine phosphatase (PTP), because the PTP
      inhibitor sodium orthovanadate mimicked the effects of Go6976. Selective blockade
      of EGF-R kinase by AG1478 [4-(3-chloroanilino)6,7-dimethoxyquinazoline] abolished
      the ERK1/2 activation induced by Go6976. Similar experiments were conducted in
      human embryonic kidney 293 cells, which express receptors for LPA and EGF but
      exhibit no significant cross-communication between them. Although Go6976 caused a
      significant increase in EGF-induced tyrosine phosphorylation of the EGF-R and
      subsequent ERK1/2 activation, it had no such effects on LPA-induced responses. In
      Chinese hamster ovary cells, which express receptors for LPA but not for EGF,
      Go6976 also had no significant effect on LPA-induced ERK1/2 activation. These
      data indicate that Go6976 potentiates agonist-induced ERK1/2 activation through
      stimulation of tyrosine phosphorylation of the EGF-R.

PMID- 15465929
TI  - What should we report to medical error reporting systems?

PMID- 15465930
TI  - Pay for performance: the best worst choice.

PMID- 15465931
TI  - The volume-quality relationship: insufficient evidence for use as a quality
      indicator.

PMID- 15465932
TI  - Why communication fails in the operating room.

PMID- 15465933
TI  - Prescribing how NHS trusts "do" quality: a recipe for committees but little
      action?

PMID- 15465934
TI  - Making sure the right patient gets the right care.

PMID- 15465935
TI  - Communication failures in the operating room: an observational classification of
      recurrent types and effects.
AB  - BACKGROUND: Ineffective team communication is frequently at the root of medical
      error. The objective of this study was to describe the characteristics of
      communication failures in the operating room (OR) and to classify their effects.
      This study was part of a larger project to develop a team checklist to improve
      communication in the OR. METHODS: Trained observers recorded 90 hours of
      observation during 48 surgical procedures. Ninety four team members participated
      from anesthesia (16 staff, 6 fellows, 3 residents), surgery (14 staff, 8 fellows,
      13 residents, 3 clerks), and nursing (31 staff). Field notes recording
      procedurally relevant communication events were analysed using a framework which
      considered the content, audience, purpose, and occasion of a communication
      exchange. A communication failure was defined as an event that was flawed in one
      or more of these dimensions. RESULTS: 421 communication events were noted, of
      which 129 were categorized as communication failures. Failure types included
      "occasion" (45.7% of instances) where timing was poor; "content" (35.7%) where
      information was missing or inaccurate, "purpose" (24.0%) where issues were not
      resolved, and "audience" (20.9%) where key individuals were excluded. 36.4% of
      failures resulted in visible effects on system processes including inefficiency,
      team tension, resource waste, workaround, delay, patient inconvenience and
      procedural error. CONCLUSION: Communication failures in the OR exhibited a common
      set of problems. They occurred in approximately 30% of team exchanges and a third
      of these resulted in effects which jeopardized patient safety by increasing
      cognitive load, interrupting routine, and increasing tension in the OR.

PMID- 15465936
TI  - Achieving progress through clinical governance? A national study of health care
      managers' perceptions in the NHS in England.
AB  - BACKGROUND: A national cross sectional study was undertaken to explore the
      perceptions concerning the importance of, and progress in, aspects of clinical
      governance among board level and directorate managers in English acute,
      ambulance, and mental health/learning disabilities (MH/LD) trusts. PARTICIPANTS:
      A stratified sample of acute, ambulance, and mental health/learning disabilities
      trusts in England (n = 100), from each of which up to 10 board level and 10
      directorate level managers were randomly sampled. METHODS: Fieldwork was
      undertaken between April and July 2002 using the Organisational Progress in
      Clinical Governance (OPCG) schedule to explore managers' perceptions of the
      importance of, and organisational achievement in, 54 clinical governance
      competency items in five aggregated domains: improving quality; managing risks;
      improving staff performance; corporate accountability; and leadership and
      collaboration. The difference between ratings of importance and achievement was
      termed a shortfall. RESULTS: Of 1916 individuals surveyed, 1177 (61.4%)
      responded. The competency items considered most important and recording highest
      perceived achievement related to corporate accountability structures and clinical
      risks. The highest shortfalls between perceived importance and perceived
      achievement were reported in joint working across local health communities,
      feedback of performance data, and user involvement. When aggregated into domains,
      greatest achievement was perceived in the assurance related areas of corporate
      accountability and risk management, with considerably less perceived achievement
      and consequently higher shortfalls in quality improvement and leadership and
      collaboration. Directorate level managers' perceptions of achievement were found
      to be significantly lower than those of their board level colleagues on all
      domains other than improving performance. No differences were found in
      perceptions of achievement between different types of trusts, or between trusts
      at different stages in the Commission for Health Improvement (CHI) review cycle.
      CONCLUSIONS: While structures and systems for clinical governance seem well
      established, there is more perceived progress in areas concerned with quality
      assurance than quality improvement. This study raises some uncomfortable
      questions about the impact of CHI review visits.

PMID- 15465937
TI  - Acceptability of identification bracelets for hospital inpatients.
AB  - OBJECTIVE: To evaluate whether hospitalised patients would agree to wear an
      identification bracelet and whether patient acceptability is improved by more
      detailed explanations or by using a code instead of a name on the bracelet.
      DESIGN: Patient survey that tested two variables in a randomised factorial
      design. Explanations about identification bracelets were given (a) with or
      without examples of situations where patient identification may be important, and
      (b) with the patient name or an anonymous code appearing on the bracelet.
      SETTING: Swiss teaching hospital where wearing of identification bracelets was
      not systematic. PARTICIPANTS: Adult patients discharged from hospital (n = 1411).
      MAIN OUTCOME MEASURES: Patients' responses to the questions: (a) should the
      hospital introduce a compulsory identification bracelet? and (b) would the
      patient agree to wear such a bracelet? RESULTS: Globally, 83.9% of patients
      thought that the hospital should introduce bracelets and 90.2% stated that they
      would agree to wear one. Providing examples increased support for both the
      hospital policy (87.9% v 79.2%, p<0.001) and personal acceptance (92.2% v 88.1%,
      p = 0.015). Whether or not the bracelet carried the patient's name or an
      anonymous code did not influence patient choice. CONCLUSIONS: The majority of
      patients were in favour of wearing an identification bracelet during their
      hospital stay. This proportion increased significantly when an explanation based
      on examples of the consequences of incorrect patient identification had been
      provided.

PMID- 15465938
TI  - Patient reports of adverse events associated with acupuncture treatment: a
      prospective national survey.
AB  - OBJECTIVE: The primary aim was to establish from acupuncture patients the type
      and frequency of adverse events they experienced and attributed to their
      treatment. Secondary aims included the measurement of patient reported adverse
      consequences arising from advice received about conventional/prescribed
      medication or from delayed conventional diagnosis and treatment. METHODS: Postal
      survey of prospectively identified acupuncture patients. One in three members of
      the British Acupuncture Council (n = 638) invited consecutive patients to
      participate in the survey. Participating patients gave baseline data and
      consented to direct follow up by the researchers at 3 months. A structured
      questionnaire was used to collect data on perceived adverse events. RESULTS: 9408
      patients gave baseline information and consent and 6348 (67%) completed 3 month
      questionnaires. Responders were not dissimilar to non-responders for all known
      characteristics. 682 patients reported at least one adverse event over 3 months,
      a rate of 107 per 1000 patients (95% CI 100 to 115). Three patients reported a
      serious adverse event. The most common events reported were severe tiredness and
      exhaustion, pain at the site of needling, and headache. Patients receiving
      acupuncture treatment that was not funded by the NHS and patients not in contact
      with a GP or hospital specialist were less likely to report adverse events (odds
      ratios 0.59 and 0.66, respectively). 199 (3%) of responding patients reported
      receiving advice about conventional/prescribed medication, six of whom reported
      adverse consequences after taking the advice. Two patients reported delayed
      conventional treatment. CONCLUSION: Patients report a range of adverse events but
      these do not prevent most patients seeking further acupuncture. This large scale
      survey supports existing evidence that acupuncture is a relatively safe
      intervention when practised by regulated practitioners.

PMID- 15465939
TI  - RCGP Quality Team Development programme: an illuminative evaluation.
AB  - BACKGROUND: There is increasing interest in quality initiatives that are locally
      owned and delivered, team based, multiprofessional, and formative. The Royal
      College of General Practitioners' Quality Team Development (QTD) programme is one
      such initiative aimed at developing primary healthcare teams and their services.
      AIMS: To evaluate QTD from the perspective of participants and assessors.
      SETTING: UK primary health care. DESIGN AND METHOD: Twelve of 14 practices and
      all four primary care organisations (PCOs) approached agreed to participate.
      Thirty four semi-structured interviews were conducted with key stakeholders. The
      interviews were taped, transcribed, and analysed using the constant comparative
      method. RESULTS: The QTD programme appears to be highly valued by participating
      organisations. Practice based respondents perceived it as acceptable and
      feasible, and reported positive changes in teamwork and patient services. They
      valued its formative, participative, and multiprofessional nature, especially the
      peer review element. PCOs saw QTD as a method of delivering on prevailing
      national policies on clinical quality and modernization agendas as well as
      promoting interorganizational collaboration. The main concerns raised were the
      workload, particularly for assessors, and maintaining the quality of the
      assessments and the programme. CONCLUSION: This qualitative study suggests
      positive benefits for participants in the QTD programme. However, such practices
      are a self-selecting innovative minority. Further research is needed on more
      typical practices to identify barriers to their participation in QTD or other
      formative, team based quality improvement programmes.

PMID- 15465940
TI  - Safety of telephone consultation for "non-serious" emergency ambulance service
      patients.
AB  - OBJECTIVE: To assess the safety of nurses and paramedics offering telephone
      assessment, triage, and advice as an alternative to immediate ambulance dispatch
      for emergency ambulance service callers classified by lay call takers as
      presenting with "non-serious" problems (category C calls). DESIGN: Data for this
      study were collected as part of a pragmatic randomised controlled trial reported
      elsewhere. The intervention arm of the trial comprised nurse or paramedic
      telephone consultation using a computerised decision support system to assess,
      triage, and advise patients whose calls to the emergency ambulance service had
      been classified as "non-serious" by call takers applying standard priority
      dispatch criteria. A multidisciplinary expert clinical panel reviewed data from
      ambulance service, accident and emergency department, hospital inpatient and
      general practice records, and call transcripts for patients triaged by nurses and
      paramedics into categories that indicated that dispatch of an emergency ambulance
      was unnecessary. All cases for which one or more members of the panel rated that
      an emergency ambulance should have been dispatched were re-reviewed by the entire
      panel for an assessment of the "life risk" that might have resulted. SETTING:
      Ambulance services in London and the West Midlands, UK. STUDY POPULATION: Of 635
      category C patients assessed by nurses and paramedics, 330 (52%) cases that had
      been triaged as not requiring an emergency ambulance were identified. MAIN
      OUTCOME MEASURES: Assessment of safety of triage decisions. RESULTS: Sufficient
      data were available from the routine clinical records of 239 (72%) subjects to
      allow review by the specialist panel. For 231 (96.7%) sets of case notes
      reviewed, the majority of the panel concurred with the nurses' or paramedics'
      triage decision. Following secondary review of the records of the remaining eight
      patients, only two were rated by the majority as having required an emergency
      ambulance within 14 minutes. For neither of these did a majority of the panel
      consider that the patient would have been at "life risk" without an emergency
      ambulance being immediately dispatched. However, the transcripts of these two
      calls indicated that the correct triage decision had been communicated to the
      patient, which suggests that the triage decision had been incorrectly entered
      into the decision support system. CONCLUSIONS: Telephone advice may be a safe
      method of managing many category C callers to 999 ambulance services. A clinical
      trial of the full implementation of this intervention is needed, large enough to
      exclude the possibility of rare adverse events.

PMID- 15465941
TI  - Patients' experiences of an open access follow up arrangement in managing
      inflammatory bowel disease.
AB  - BACKGROUND: Improving access is a key policy issue in improving quality of care
      and extending patient choice and participation. People's experience of changing
      from fixed outpatient appointments to more flexible direct access arrangements
      for chronic disease has been underexplored. OBJECTIVES: To examine patients'
      views on using an open system of access compared with fixed outpatient
      appointments as part of a guided self-management intervention for inflammatory
      bowel disease (IBD). DESIGN: Embedded qualitative study undertaken alongside a
      randomised controlled trial. Semi-structured interviews were undertaken to obtain
      an in depth understanding of patients' experience of the change in access
      arrangements. PARTICIPANTS: A purposive sample (n = 30) was drawn from the
      intervention group (n = 700) according to a range of responses to the trial
      baseline and follow up quantitative measures. RESULTS: 28 interviews were
      included in the analysis. Compared with the previous system of fixed
      appointments, preference for the new open access system was based on enhanced
      personal control in contacting services and the view that it fitted better with
      everyday routine management and the requirement for urgent medical contact when
      symptoms fail to respond to medication. Preference for retaining fixed
      appointments was based on a sense of security from gaining access which did not
      require the individual to initiate the request for medical help. CONCLUSIONS:
      Open access may fit better with patients' self-management of their condition and
      everyday routines, roles and responsibilities. Ensuring that outpatient
      organisational arrangements and personnel are responsive to patient initiated
      requests for appointments is likely to impact on the acceptability of this type
      of access arrangement. Some people may continue to prefer the fixed appointment
      system which should be retained if patient choice is to be respected.

PMID- 15465942
TI  - Does it matter what a hospital is "high volume" for? Specificity of hospital
      volume-outcome associations for surgical procedures: analysis of administrative
      data.
AB  - OBJECTIVE: To determine whether the improved outcome of a surgical procedure in
      high volume hospitals is specific to the volume of the same procedure. DESIGN AND
      SETTING: Analysis of secondary data in Ontario, Canada. PARTICIPANTS: Patients
      having an oesophagectomy, colorectal resection for cancer,
      pancreaticoduodenectomy, major lung resection for cancer, or repair of an
      unruptured abdominal aortic aneurysm between 1994 and 1999. MAIN OUTCOME
      MEASURES: Odds ratio for death within 30 days of surgery in relation to the
      hospital volume of the same surgical procedure and the hospital volume of the
      other four procedures. Estimates were adjusted for age, sex, and comorbidity and
      accounted for hospital level clustering. RESULTS: With the exception of
      colorectal resection, 30 day mortality seemed to be inversely related not only to
      the hospital volume of the same procedure but also to the hospital volume of most
      of the other procedures. In some cases the effect of the volume of a different
      procedure was stronger than the effect of the volume of the same procedure. For
      example, the association of mortality from pancreaticoduodenectomy with hospital
      volume of lung resection (odds ratio for death in hospitals with a high volume of
      lung resection compared with low volume 0.36, 95% confidence interval 0.23 to
      0.57) was much stronger than the association of mortality from
      pancreaticoduodenectomy with hospital volume of pancreaticoduodenectomy (0.76,
      0.44 to 1.32). CONCLUSION: The inverse association between high volume of
      procedure and risk of operative death is not specific to the volume of the
      procedure being studied.

PMID- 15465943
TI  - Use of a preprinted sticker to improve the prescribing of prophylactic
      antibiotics for hip fracture surgery.
AB  - PROBLEM: Antibiotic prophylaxis has been shown to reduce the number of
      postoperative infections following surgery for hip fracture. At Auckland Hospital
      the policy for antibiotic prophylaxis for hip fracture surgery is for the patient
      to receive the first dose of antibiotic at the induction of anaesthesia followed
      by two more doses at 8 hour intervals. A previous audit found that patients often
      received too many doses of antibiotic. A retrospective audit was performed of 100
      patients undergoing surgery for a hip fracture. The primary problem was over
      prescribing; 68 patients (68%) received more than three doses. The number of
      patients who received three doses according to the guidelines was 29 (29%, 95% CI
      21 to 40). SETTING: Auckland Hospital which provides acute orthopaedic services
      for a population of 500,000. STRATEGY FOR CHANGE: A sticker was introduced with
      the prescription printed on it. The sticker was applied to the medication chart
      by the anaesthetist when the initial dose of antibiotic was given. Charts of a
      further 100 patients were reviewed after the introduction of the sticker and
      compared with those from another hospital in Auckland where the sticker was not
      used. EFFECTS OF CHANGE: The number of patients who received three doses, in
      accordance with the guidelines, improved to 74 (74%, 95% CI 64 to 82, p<0.001).
      These changes were observed even though the sticker was only used in 44 patients
      (44%, 95% CI 34 to 54). At the other hospital the number of patients who received
      three doses was 10 (20%, 95% CI 10 to 42) and 13 (26%, 95% CI 15 to 40, p = 0.37)
      for the same two periods. LESSONS LEARNT: The use of a preprinted sticker is a
      simple intervention which improves the use of antibiotic prophylaxis at the time
      of surgery. This improvement occurred even though the sticker was used in
      slightly fewer than half the cases.

PMID- 15465944
TI  - Beyond usability: designing effective technology implementation systems to
      promote patient safety.
AB  - Evidence is emerging that certain technologies such as computerized provider
      order entry may reduce the likelihood of patient harm. However, many technologies
      that should reduce medical errors have been abandoned because of problems with
      their design, their impact on workflow, and general dissatisfaction with them by
      end users. Patient safety researchers have therefore looked to human factors
      engineering for guidance on how to design technologies to be usable (easy to use)
      and useful (improving job performance, efficiency, and/or quality). While this is
      a necessary step towards improving the likelihood of end user satisfaction, it is
      still not sufficient. Human factors engineering research has shown that the
      manner in which technologies are implemented also needs to be designed carefully
      if benefits are to be realized. This paper reviews the theoretical knowledge on
      what leads to successful technology implementation and how this can be translated
      into specifically designed processes for successful technology change. The
      literature on diffusion of innovations, technology acceptance, organisational
      justice, participative decision making, and organisational change is reviewed and
      strategies for promoting successful implementation are provided. Given the rapid
      and ever increasing pace of technology implementation in health care, it is
      critical for the science of technology implementation to be understood and
      incorporated into efforts to improve patient safety.

PMID- 15465945
TI  - Effectiveness of a simulator in training anesthesiology residents. 1969.
AB  - The educational potential of a computer-controlled patient simulator was tested
      by the University of Southern California School of Medicine. The results of the
      experiment suggest unequivocally that there is a twofold advantage to the use of
      such a simulator in training anesthesiology residents in the skill of
      endotracheal intubation: (a) residents achieve proficiency levels in a smaller
      number of elapsed days of training, thus effecting a saving of time in the
      training of personnel, and (b) residents achieve a proficiency level in a smaller
      number of trials in the operating room, thus posing significantly less threat to
      patient safety. The small number of subjects in the study and the large within
      group variability were responsible for a lack of statistical significance in 4 of
      6 of the analyses performed; however, all differences were substantial and in the
      hypothesized direction. Thus, despite the narrowly circumscribed tasks to be
      learned by the experimental subjects, the findings suggest that the use of
      simulation devices should be considered in planning for future education and
      training not only in medicine but in other health care professions as well.

PMID- 15465946
TI  - Will simulation fly in medicine as it has in aviation?

PMID- 15465947
TI  - Management of colorectal cancers.
AB  - The management of colorectal cancers, published in a recent issue of Effective
      Health Care, is reviewed.

PMID- 15465948
TI  - From the runway to the airway and beyond.

PMID- 15465950
TI  - Identifying and reducing errors with surgical simulation.
AB  - The major determinant of a patient's safety and outcome is the skill and judgment
      of the surgeon. While knowledge base and decision processing are evaluated during
      residency, technical skills-which are at the core of the profession-are not
      evaluated. Innovative state of the art simulation devices that train both
      surgical tasks and skills, without risk to patients, should allow for the
      detection and analysis of errors and "near misses". Studies have validated the
      use of a sophisticated endoscopic sinus surgery simulator (ES3) for training
      residents on a procedural basis. Assessments are proceeding as to whether the
      integration of a comprehensive ES3 training programme into the residency
      curriculum will have long term effects on surgical performance and patient
      outcomes. Using various otolaryngology residencies, subjects are exposed to
      mentored training on the ES3 as well as to minimally invasive trainers such as
      the MIST-VR. Technical errors are identified and quantified on the simulator and
      intraoperatively. Through a web based database, individual performance can be
      compared against a national standard. An upgraded version of the ES3 will be
      developed which will support patient specific anatomical models. This advance
      will allow study of the effects of simulated rehearsal of patient specific
      procedures (mission rehearsal) on patient outcomes and surgical errors during the
      actual procedure. The information gained from these studies will help usher in
      the next generation of surgical simulators that are anticipated to have
      significant impact on patient safety.

PMID- 15465949
TI  - A brief history of the development of mannequin simulators for clinical education
      and training.
AB  - Simulation for medical and healthcare applications, although still in a
      relatively nascent stage of development, already has a history that can inform
      the process of further research and dissemination. The development of mannequin
      simulators used for education, training, and research is reviewed, tracing the
      motivations, evolution to commercial availability, and efforts toward assessment
      of efficacy of those for teaching cardiopulmonary resuscitation, cardiology
      skills, anaesthesia clinical skills, and crisis management. A brief overview of
      procedural simulators and part-task trainers is also presented, contrasting the
      two domains and suggesting that a thorough history of the 20+ types of simulator
      technologies would provide a useful overview and perspective. There has been
      relatively little cross fertilisation of ideas and methods between the two
      simulator domains. Enhanced interaction between investigators and integration of
      simulation technologies would be beneficial for the dissemination of the concepts
      and their applications.

PMID- 15465951
TI  - The future vision of simulation in health care.
AB  - Simulation is a technique-not a technology-to replace or amplify real experiences
      with guided experiences that evoke or replicate substantial aspects of the real
      world in a fully interactive manner. The diverse applications of simulation in
      health care can be categorised by 11 dimensions: aims and purposes of the
      simulation activity; unit of participation; experience level of participants;
      health care domain; professional discipline of participants; type of knowledge,
      skill, attitudes, or behaviours addressed; the simulated patient's age;
      technology applicable or required; site of simulation; extent of direct
      participation; and method of feedback used. Using simulation to improve safety
      will require full integration of its applications into the routine structures and
      practices of health care. The costs and benefits of simulation are difficult to
      determine, especially for the most challenging applications, where long term use
      may be required. Various driving forces and implementation mechanisms can be
      expected to propel simulation forward, including professional societies,
      liability insurers, health care payers, and ultimately the public. The future of
      simulation in health care depends on the commitment and ingenuity of the health
      care simulation community to see that improved patient safety using this tool
      becomes a reality.

PMID- 15465952
TI  - The simulated operating theatre: comprehensive training for surgical teams.
AB  - Surgical excellence is traditionally defined in terms of technical performance,
      with little regard for the importance of interpersonal communication and
      leadership skills. Studies in the aviation industry have stressed the role of
      human factors in causing error and, in an attempt to reduce the occurrence of
      adverse events, led to the organisation of simulation based training scenarios.
      Similar strategies have recently been employed for the surgical team with the
      development of a simulated operating theatre project. This enables technical and
      non-technical performance of the surgeon and circulating staff to be assessed by
      experts situated in an adjacent control room, and provides an opportunity for
      constructive feedback. The scenarios have good face validity and junior surgeons
      can benefit from the process of learning new technical skills in a realistic
      environment. The effect of external influences such as distractions, new
      technology, or a crisis scenario can also be defined, with the ultimate aim of
      reducing the number of adverse events arising in the real operating room.

PMID- 15465953
TI  - Developing observational measures of performance in surgical teams.
AB  - Team performance is increasingly recognised as an essential foundation of good
      surgical care and a determinant of good surgical outcome. To understand team
      performance and to develop team training, reliable and valid measures of team
      performance are necessary. Currently there is no firm consensus on how to measure
      teamwork, partly because of a lack of empirical data to validate measures. The
      input-process-output model provides a framework for surgical team studies.
      Objective observational measures are needed in surgery as a basis for
      interdisciplinary team assessment and training. The "observational teamwork
      assessment for surgery" (OTAS) tool assesses two facets of the surgical process.
      Observer 1 monitors specific tasks carried out by team members, under the
      categories patient, environment, equipment, provisions, and communications.
      Observer 2 uses a behavioural observation scale to rate behaviour for the three
      surgical phases (pre-operative, operative, and post-operative) with components of
      teamwork: cooperation, leadership, coordination, awareness, and communication.
      Illustrative data from an initial series of 50 cases is presented here. The OTAS
      tool enables two independent observers, a surgeon and psychologist, to record
      detailed information both on what the theatre team does and how they do it, and
      has the potential to identify constraints on performance that might relate to
      surgical outcome.

PMID- 15465954
TI  - Simulations in the United States Medical Licensing Examination (USMLE).
AB  - Over the last several years there has been much attention focused on the
      detection and remediation of problems that pose potential threats to patient
      safety and that interfere with the provision of effective care. It has been noted
      that changes in medical education and assessment are integral to eventual
      improvement in this area. Within the assessment system used to licence physicians
      in the United States, there has been an evolution of assessment formats intended
      to improve the measurement of knowledge and skills, including the recent
      development of computer based patient simulations and clinical skills
      assessments. A number of new testing formats intended to further enhance
      assessment of critical knowledge and skills will be available in the near future.

PMID- 15465955
TI  - Using standardised patients in an objective structured clinical examination as a
      patient safety tool.
AB  - Standardised patients (SPs) are a powerful form of simulation that has now become
      commonplace in training and assessment in medical education throughout the world.
      Standardised patients are individuals, with or without actual disease, who have
      been trained to portray a medical case in a consistent manner. They are now the
      gold standard for measuring the competence of physicians and other health
      professionals, and the quality of their practice. A common way in which SPs are
      used in performance assessment has been as part of an objective structured
      clinical examination (OSCE). The use of an SP based OSCE can be a powerful tool
      in measuring continued competence in human reliability and skill performance
      where such skills are a critical attribute to maintaining patient safety. This
      article will describe how an OSCE could be used as a patient safety tool based on
      cases derived from actual events related to postdonation information in the blood
      collection process. The OSCE was developed as a competency examination for health
      history takers. Postdonation information events in the blood collection process
      account for the majority of errors reported to the US Food and Drug
      Administration. SP based assessment is an important patient safety tool that
      could be applied to a variety of patient safety settings and situations, and
      should be considered an important weapon in the war on medical error and patient
      harm.

PMID- 15465956
TI  - The use of simulation for training teamwork skills in health care: how low can
      you go?
AB  - High fidelity simulation has become a popular technique for training teamwork
      skills in high risk industries such as aviation, health care, and nuclear power
      production. Simulation is a powerful training tool because it allows the trainer
      to systematically control the schedule of practice, presentation of feedback, and
      introduction (or suppression) of environmental distractions within a safe,
      controlled learning environment. Unfortunately, many within the training
      community have begun to use the terms simulation and high fidelity simulation
      almost synonymously. This is unfortunate because doing so overemphasises the
      instructional technology to the detriment of more substantive issues, such as the
      training's goals, content, and design. It also perpetuates several myths:
      simulation fidelity is unidimensional, or higher levels of simulation fidelity
      lead to increased training effectiveness. The authors propose a typology of
      simulation fidelity and provide examples of how the different classes of
      simulation have been successfully used to train teamwork skills in high risk
      industries. Guidelines are also provided to maximise the usefulness of simulation
      for training teamwork skills in health care.

PMID- 15465957
TI  - Translating teamwork behaviours from aviation to healthcare: development of
      behavioural markers for neonatal resuscitation.
AB  - Improving teamwork in healthcare may help reduce and manage errors. This paper
      takes a step toward that goal by (1) proposing a set of teamwork behaviours, or
      behavioural markers, for neonatal resuscitation; (2) presenting a data form for
      recording observations about these markers; and (3) comparing and contrasting
      different sets of teamwork behaviours that have been developed for healthcare.
      Data from focus groups of neonatal providers, surveys, and video recordings of
      neonatal resuscitations were used to identify some new teamwork behaviours, to
      translate existing aviation team behaviours to this setting, and to develop a
      data collection form. This behavioural marker audit form for neonatal
      resuscitation lists and defines 10 markers that describe specific, observable
      behaviours seen during the resuscitation of newborn infants. These markers are
      compared with those developed by other groups. Future research should determine
      the relations among these behaviours and errors, and test their usefulness in
      measuring the impact of team training interventions.

PMID- 15465958
TI  - Objective measures of situation awareness in a simulated medical environment.
AB  - One major limitation in the use of human patient simulators is a lack of
      objective, validated measures of human performance. Objective measures are
      necessary if simulators are to be used to evaluate the skills and training of
      medical practitioners and teams or to evaluate the impact of new processes or
      equipment design on overall system performance. Situation awareness (SA) refers
      to a person's perception and understanding of their dynamic environment. This
      awareness and comprehension is critical in making correct decisions that
      ultimately lead to correct actions in medical care settings. An objective measure
      of SA may be more sensitive and diagnostic than traditional performance measures.
      This paper reviews a theory of SA and discusses the methods required for
      developing an objective measure of SA within the context of a simulated medical
      environment. Analysis and interpretation of SA data for both individual and team
      performance in health care are also presented.

PMID- 15465959
TI  - The complexity of team training: what we have learned from aviation and its
      applications to medicine.
AB  - Errors in health care that compromise patient safety are tied to latent failures
      in the structure and function of systems. Teams of people perform most care
      delivered today, yet training often remains focused on individual
      responsibilities. Training programmes for all healthcare workers need to increase
      the educational experience of working in interdisciplinary teams. The
      complexities of team training require a multifunctional (systems) approach, which
      crosses organisational divisions to allow communication, accountability, and
      creation and maintenance of interdisciplinary teams. This report identifies
      challenges for medical education in performing the research, identifying
      performance measurements, and modifying educational curricula for the advancement
      of interdisciplinary teams, based on the complexity of team training identified
      in commercial aviation.

PMID- 15465960
TI  - Identifying and training non-technical skills for teams in acute medicine.
AB  - The aviation domain provides a better analogy for the "temporary" teams that are
      found in acute medical specialities than industrial or military teamwork research
      based on established teams. Crew resource management (CRM) training, which
      emphasises portable skills (for whatever crew a pilot is rostered to on a given
      flight), has been recognised to have potential application in medicine,
      especially for teams in the operating theatre, intensive care unit, and emergency
      room. Drawing on research from aviation psychology that produced the behavioural
      marker system NOTECHS for rating European pilots' non-technical skills for
      teamwork on the flightdeck, this paper outlines the Anaesthetists Non-Technical
      Skills behavioural rating system for anaesthetists working in operating theatre
      teams. This taxonomy was used as the design basis for a training course, Crisis
      Avoidance Resource Management for Anaesthetists used to develop these skills,
      based in an operating theatre simulator. Further developments of this training
      programme for teams in emergency medicine are outlined.

PMID- 15465961
TI  - The human factor: the critical importance of effective teamwork and communication
      in providing safe care.
AB  - Effective communication and teamwork is essential for the delivery of high
      quality, safe patient care. Communication failures are an extremely common cause
      of inadvertent patient harm. The complexity of medical care, coupled with the
      inherent limitations of human performance, make it critically important that
      clinicians have standardised communication tools, create an environment in which
      individuals can speak up and express concerns, and share common "critical
      language" to alert team members to unsafe situations. All too frequently,
      effective communication is situation or personality dependent. Other high
      reliability domains, such as commercial aviation, have shown that the adoption of
      standardised tools and behaviours is a very effective strategy in enhancing
      teamwork and reducing risk. We describe our ongoing patient safety implementation
      using this approach within Kaiser Permanente, a non-profit American healthcare
      system providing care for 8.3 million patients. We describe specific clinical
      experience in the application of surgical briefings, properties of high
      reliability perinatal care, the value of critical event training and simulation,
      and benefits of a standardised communication process in the care of patients
      transferred from hospitals to skilled nursing facilities. Additionally, lessons
      learned as to effective techniques in achieving cultural change, evidence of
      improving the quality of the work environment, practice transfer strategies,
      critical success factors, and the evolving methods of demonstrating the benefit
      of such work are described.

PMID- 15465962
TI  - Implementation of team training in medical education in Denmark.
AB  - In the field of medicine, team training aiming at improving team skills such as
      leadership, communication, co-operation, and followership at the individual and
      the team level seems to reduce risk of serious events and therefore increase
      patient safety. The preferred educational method for this type of training is
      simulation. Team training is not, however, used routinely in the hospital. In
      this paper, we describe a framework for the development of a team training course
      based on need assessment, learning objectives, educational methods including full
      scale simulation and evaluations strategies. The use of this framework is
      illustrated by the present multiprofessional team training in advanced cardiac
      life support, trauma team training and neonatal resuscitation in Denmark. The
      challenges of addressing all aspects of team skills, the education of the
      facilitators, and establishment of evaluation strategies to document the effect
      of the different types of training on patient safety are discussed.

PMID- 15465963
TI  - How to turn a team of experts into an expert medical team: guidance from the
      aviation and military communities.
AB  - There is no question that interdisciplinary teams are becoming ubiquitous in
      healthcare. It is also true that experts do not necessarily combine to make an
      expert team. However when teams work well they can serve as adaptive systems that
      allow organisations to mitigate errors within complex domains, thereby increasing
      safety. The medical community has begun to recognise the importance of teams and
      as such has begun to implement team training interventions. Over the past 20
      years the military and aviation communities have made a large investment in
      understanding teams and their requisite training requirements. There are many
      lessons that can be learned from these communities to accelerate the impact of
      team training within the medical community. Therefore, the purpose of the current
      paper is to begin to translate some of the lessons learned from the military and
      aviation communities into practical guidance that can be used by the medical
      community.

PMID- 15465964
TI  - Genes outside the S supergene suppress S functions in buckwheat (Fagopyrum
      esculentum).
AB  - BACKGROUND AND AIMS: Common buckwheat (Fagopyrum esculentum) is a dimorphic self
      incompatible plant with either pin or thrum flowers. The S supergene is thought
      to govern self-incompatibility, flower morphology and pollen size in buckwheat.
      Two major types of self-fertile lines have been reported. One is a type with long
      homostyle flowers, Kyukei SC2 (KSC2), and the other is a type with short
      homostyle flowers, Pennline 10. To clarify whether the locus controlling flower
      morphology and self-fertility of Pennline 10 is the same as that of KSC2, pollen
      tube tests and genetic analysis have been performed. METHODS: Pollen tube growth
      was assessed in the styles and flower morphology of KSC2, Pennline 10, F1 and F2
      plants that were produced by the crosses between plants with pin or thrum and
      Pennline 10. KEY RESULTS: Pollen tubes of Pennline 10 reached ovules of all
      flower types. The flower morphology of F1 plants produced by the cross between
      thrum and Pennline 10 were thrum or pin, and when pin plants were used as
      maternal plants, all the F1 plants were pin. Both plants with pin or short-pin
      flowers, whose ratio of style length to anther height was smaller than that of
      pin, appeared in F2 populations of thrum x Pennline 10 as well as in those of pin
      x Pennline 10. CONCLUSION: The results suggest that Pennline 10 possesses the s
      allele as pin does, not an allele produced by the recombination in the S
      supergene, and that the short style length of Pennline 10 is controlled by
      multiple genes outside the S supergene.

PMID- 15465965
TI  - The mosaic of addiction.

PMID- 15465966
TI  - Dimensions of personality pathology: an alternative to the five-factor model.
AB  - OBJECTIVE: Researchers have advocated replacing the DSM-IV classification of
      personality disorders with an alternative diagnostic system based on the five
      factor model. This study evaluates the clinical comprehensiveness of the five
      factor model and addresses the broader question of how many factors, and which
      factors, are necessary to understand personality pathology. METHOD: A national
      sample of 530 psychiatrists and clinical psychologists used the Shedler-Westen
      Assessment Procedure (SWAP-200) to provide detailed psychological descriptions of
      patients with personality disorder diagnoses. The SWAP-200 is a 200-item
      instrument designed to capture the richness and complexity of clinical
      observations while also providing quantifiable data for research. We used factor
      analysis to identify dimensions of personality relevant to understanding
      personality pathology. RESULTS: The five-factor structure replicated in a content
      restricted subset of 60 SWAP-200 items. However, factor analysis of the full SWAP
      200 yielded a conceptually richer factor solution that did not resemble the five
      factor model. The analysis identified 12 clinically relevant personality
      dimensions labeled psychological health, psychopathy, hostility, narcissism,
      emotional dysregulation, dysphoria, schizoid orientation, obsessionality, thought
      disorder, oedipal conflict (histrionic sexualization), dissociation, and sexual
      conflict. CONCLUSIONS: The five-factor model represents a sound distillation of
      the personality constructs used by laypersons. However, it omits key clinical
      constructs and may not capture the complexity of personality syndromes seen in
      clinical practice. The SWAP-200 factors may provide a framework for studying
      personality pathology that is both empirically grounded and clinically relevant.

PMID- 15465967
TI  - History, memory, and profession: a view of American psychiatry through APA
      presidential addresses, 1883-2003.
AB  - The address of the retiring president of the American Psychiatric Association has
      been a traditional part of the annual meeting of the association since 1883. The
      presidential address, which has explicitly been exempted from general discussion
      or criticism, has become an opportunity for the elected leader of the association
      to reflect on the state of the profession. Over the last 120 years, the
      presidents of the association have themselves engaged with the history of
      psychiatry in ways that reflect the changes in psychiatry of the time. In the
      process, memory has served a professionalizing purpose, as some aspects of
      psychiatry's history have been remembered while others have not. In the
      presidential addresses, history is not just a story about the past but also a
      story about psychiatry's self-definition and its future.

PMID- 15465968
TI  - GABA neurons in the human prefrontal cortex.

PMID- 15465969
TI  - Konrad Lorenz, 1903-1989.

PMID- 15465973
TI  - Altered NMDA glutamate receptor antagonist response in individuals with a family
      vulnerability to alcoholism.
AB  - OBJECTIVE: A family history of alcoholism is a risk factor for the development of
      ethanol dependence. Ethanol is an antagonist of the N-methyl-d-aspartate (NMDA)
      glutamate receptor, and alterations in NMDA receptor function are thought to be
      involved in ethanol abuse and dependence. The purpose of this study was to
      determine in healthy individuals with no ethanol dependence whether response to
      the NMDA receptor antagonist ketamine would differentiate those with a family
      history of ethanol dependence from those without such a family history. METHOD:
      Healthy subjects between the ages of 21 and 30 received 40-minute intravenous
      infusions of saline, low-dose ketamine (0.1 mg/kg), and high-dose ketamine (0.5
      mg/kg) on three separate test days in a randomized order under double-blind
      conditions. The healthy individuals with at least one first-degree relative and
      another first- or second-degree relative with ethanol dependence (N=16) were
      compared with those who had no family history of ethanol dependence in any first-
      or second-degree relative (N=29). Outcome measures included the Brief Psychiatric
      Rating Scale, Clinician-Administered Dissociative States Scale, verbal fluency,
      Hopkins Verbal Learning Test, a biphasic alcohol effects scale, visual analog
      scales of mood states, and ketamine levels. RESULTS: During ketamine infusion,
      individuals with a family history of ethanol dependence showed an attenuated
      response in terms of perceptual alterations and dysphoric mood relative to those
      without such a family history. CONCLUSIONS: These data suggest that alterations
      in NMDA receptor function may contribute to subjective response to ethanol and
      therefore also to the risk of developing alcoholism.

PMID- 15465974
TI  - Correlation between dopamine D(2) receptors in the ventral striatum and central
      processing of alcohol cues and craving.
AB  - OBJECTIVE: Alcohol and other drugs of abuse stimulate dopamine release in the
      ventral striatum, which includes the nucleus accumbens, a core region of the
      brain reward system, and reinforce substance intake. Chronic alcohol intake is
      associated with down-regulation of central dopamine D(2) receptors, and delayed
      recovery of D(2) receptor sensitivity after detoxification is positively
      correlated with high risk for relapse. Prolonged D(2) receptor dysfunction in the
      ventral striatum may interfere with a dopamine-dependent error detection signal
      and bias the brain reward system toward excessive attribution of incentive
      salience to alcohol-associated stimuli. METHOD: Multimodal imaging, with the
      radioligand [(18)F]desmethoxyfallypride and positron emission tomography as well
      as functional magnetic resonance imaging (fMRI), was used to compare 11
      detoxified male alcoholics with 13 healthy men. The authors measured the
      association of D(2)-like dopamine receptors in the ventral striatum with alcohol
      craving and central processing of alcohol cues. RESULTS: Activation of the medial
      prefrontal cortex and striatum by alcohol-associated stimuli, relative to
      activation by neutral visual stimuli, was greater in the detoxified alcoholics
      than in the healthy men. The alcoholics displayed less availability of D(2)-like
      receptors in the ventral striatum, which was associated with alcohol craving
      severity and with greater cue-induced activation of the medial prefrontal cortex
      and anterior cingulate as assessed with fMRI. DISCUSSION: In alcoholics,
      dopaminergic dysfunction in the ventral striatum may attribute incentive salience
      to alcohol-associated stimuli, so that alcohol cues elicit craving and excessive
      activation of neural networks associated with attention and behavior control.

PMID- 15465975
TI  - Alcohol dependence and use of treatment services among women in the community.
AB  - OBJECTIVE: This study examined the extent and characteristics of alcohol
      dependence and the perceived need for and use of alcohol treatment services among
      women compared with men in a nonclinical sample of adults 18-64 years of age.
      METHOD: Data were drawn from the 1999 National Household Survey on Drug Abuse.
      The authors calculated rates and correlates of alcohol dependence and treatment
      among adult alcohol users in this sample. RESULTS: About 3% of the women in the
      survey met criteria for DSM-IV alcohol dependence in the previous year. About 13%
      of these women received alcohol treatment services in the same period. Only 8% of
      the women who did not receive treatment perceived a need for treatment. Younger
      women-those who were 18-25 years of age-were more likely to be dependent on
      alcohol but less likely to perceive a need for treatment or to use treatment
      services. Among alcohol-dependent women who received no treatment, those with a
      family income of 75,000 US dollars or more, those who had two or more children
      living with them, and those who were not dependent on psychotherapeutic
      medications were less likely to perceive a need for help. CONCLUSIONS: There were
      no significant differences between men and women in use of treatment services,
      location of services received, and perceived need for treatment. However,
      correlates of treatment service use varied somewhat by gender. These findings
      suggest that the goal of efforts to reduce barriers to alcohol treatment services
      should be to change people's attitudes toward alcohol abuse and seeking
      professional help.

PMID- 15465976
TI  - Interaction of COMT (Val(108/158)Met) genotype and olanzapine treatment on
      prefrontal cortical function in patients with schizophrenia.
AB  - OBJECTIVE: Deficits in working memory and in prefrontal cortical physiology are
      important outcome measures in schizophrenia, and both have been associated with
      dopamine dysregulation and with a functional polymorphism (Val(108/158)Met) in
      the catechol O-methyltransferase (COMT) gene that affects dopamine inactivation
      in the prefrontal cortex. The purpose of the present study was to evaluate in
      patients with schizophrenia the effect of COMT genotype on symptom variation,
      working memory performance, and prefrontal cortical physiology in response to
      treatment with an atypical antipsychotic drug. METHOD: Thirty patients with acute
      untreated schizophrenia were clinically evaluated with the Positive and Negative
      Syndrome Scale, underwent COMT Val/Met genotyping, and entered an 8-week
      prospective study of olanzapine treatment. Twenty patients completed two 3-T
      functional magnetic resonance imaging scans at 4 and 8 weeks during performance
      of N-back working memory tasks. RESULTS: There was a significant interaction of
      COMT genotype and the effects of olanzapine on prefrontal cortical function. Met
      allele load predicted improvement in working memory performance and prefrontal
      physiology after 8 weeks of treatment. A similar effect was found also for
      negative symptoms assessed with the Positive and Negative Syndrome Scale.
      CONCLUSIONS: These results suggest that a genetically determined variation in
      prefrontal dopamine catabolism impacts the therapeutic profile of olanzapine.

PMID- 15465977
TI  - Genetic load on amygdala hypofunction during sadness in nonaffected brothers of
      schizophrenia patients.
AB  - OBJECTIVE: In a previous study, the authors reported that patients with
      schizophrenia show subcortical-limbic hypoactivity during sadness. In this study,
      they capitalized on those findings in order to assess the genetic influence of
      negative mood experience in schizophrenia patients. Brain activity was measured
      during mood induction in patients with schizophrenia and their first-degree
      nonaffected relatives. METHOD: Functional magnetic resonance imaging was used to
      investigate 13 male patients with schizophrenia, their nonaffected brothers
      (N=13), and a group of 26 individually matched healthy subjects unrelated to the
      siblings during induction of sad and happy moods as well as during a cognitive
      control task. A regional analysis was applied to investigate a possible
      subcortical-limbic dysfunction in relatives. RESULTS: Mood induction was
      successful in all groups according to subjective ratings. During sadness
      induction, the patients and their nonaffected siblings demonstrated less activity
      in the amygdala compared with the healthy group of nonrelatives. Other regions of
      interest, such as the left orbitofrontal cortex, the left superior temporal
      cortex, and the left precuneus/posterior cingulate revealed significant group
      differences only between patients and nonrelated healthy subjects. During
      positive mood induction, no group differences could be found in the amygdala.
      CONCLUSIONS: Following induction of sad mood, both patients with schizophrenia
      and their nonaffected brothers displayed reduced brain activity in the amygdala.
      Such hypoactivity is likely to represent a genetic influence and indicates that
      efficient compensatory mechanisms capable of preventing the onset of the illness
      must exist in nonaffected relatives.

PMID- 15465978
TI  - High concordance of bipolar I disorder in a nationwide sample of twins.
AB  - OBJECTIVE: The few studies of bipolar I disorder in twins have consistently
      emphasized the genetic contribution to disease liability. The authors report what
      appears to be the first twin study of bipolar I disorder involving a population
      based twin sample, in which the diagnoses were made by using structured, personal
      interviews. METHOD: All Finnish same-sex twins (N=19,124) born from 1940 to 1957
      were screened for a diagnosis of bipolar I disorder as recorded in the National
      Hospital Discharge Register between 1969 and 1991 or self-reported in surveys of
      the Finnish Twin Cohort in 1975, 1981, and 1990. Thirty-eight pairs were thereby
      identified and invited to participate in the study; the participation rate was
      68%. Lifetime diagnoses were made by using the Structured Clinical Interview for
      DSM-IV. The authors calculated probandwise and pairwise concordances and
      correlations in liability and applied biometrical model fitting. RESULTS: The
      probandwise concordance rates were 0.43 (95% CI=0.10 to 0.82) for monozygotic
      twins and 0.06 (95% CI=0.00 to 0.27) for dizygotic twins. The correlations in
      liability were 0.85 and 0.41, respectively. The model with no familial
      transmission was rejected. The best-fitting model was the one in which genetic
      and specific environmental factors explained the variance in liability, with a
      heritability estimate of 0.93 (95% CI=0.69 to 1.00). CONCLUSIONS: The high
      heritability of bipolar disorder was demonstrated in a nationwide population
      based twin sample assessed with structured personal interviews.

PMID- 15465979
TI  - Varied effects of atypical neuroleptics on P50 auditory gating in schizophrenia
      patients.
AB  - OBJECTIVE: Sensory gating deficits found in schizophrenia can be assessed by
      using a paired auditory stimulus paradigm to measure auditory evoked response.
      The ratio of the P50 response amplitude of the second or test stimulus to that of
      the first or conditioning stimulus is expressed as a percentage. Normal subjects
      generally suppress the second response and typically have ratios of less than
      40%. Subjects with schizophrenia and half their first-degree relatives have
      deficits in sensory gating, with P50 ratios that are generally greater than 50%.
      Treatment with typical neuroleptics does not reverse this deficit. However,
      previous studies have shown that treatment with clozapine, an atypical
      neuroleptic, ameliorates this deficit in clinically responsive patients. This
      study sought to determine whether other atypical neuroleptics improve P50 ratios.
      METHOD: P50 evoked potential recordings were obtained from 132 patients with
      schizophrenia and 177 healthy comparison subjects. Eighty-eight patients were
      being treated with atypical neuroleptics (clozapine [N=26], olanzapine [N=31],
      risperidone [N=22], and quetiapine [N=9]). Thirty-four patients were taking
      typical neuroleptics, and 10 were unmedicated. RESULTS: Healthy subjects
      exhibited P50 suppression that was significantly better than the schizophrenia
      patients receiving typical neuroleptics (mean=19.8% [SD=21.0%] versus 110.1%
      [SD=87.9%]). Patients receiving atypical neuroleptics had a mean P50 ratio that
      fell between these two means (mean=70.4%, SD=53.7%). When patients treated with
      different atypical neuroleptics were compared, only the clozapine group had mean
      P50 ratios that were in the normal range. All other groups exhibited auditory P50
      response inhibition that was significantly poorer than that of the healthy
      subjects. CONCLUSIONS: Improvement in P50 gating appears to be greatest in
      patients treated with clozapine.

PMID- 15465980
TI  - Reduced basal ganglia volumes after switching to olanzapine in chronically
      treated patients with schizophrenia.
AB  - OBJECTIVE: A follow-up study of patients with schizophrenia was conducted to
      examine change in striatal volumes and extrapyramidal symptoms after a change in
      medication. METHOD: Thirty-seven patients with schizophrenia and 23 healthy
      volunteers were examined. Patients at baseline receiving typical antipsychotics
      (N=10) or risperidone but exhibiting limited response (N=13) were switched to
      treatment with olanzapine. Patients receiving risperidone and exhibiting a good
      response (N=14) continued treatment with risperidone. Caudate, putamen, and
      pallidal volumes were assessed with magnetic resonance imaging. The
      Extrapyramidal Symptoms Rating Scale was used to assess clinical signs and
      symptoms. RESULTS: At baseline, basal ganglia volumes in patients treated with
      typical antipsychotics were greater than in healthy subjects (putamen: 7.0%
      larger; globus pallidus: 20.7% larger). After the switch to olanzapine, putamen
      and globus pallidus volumes decreased (9.8% and 10.7%, respectively) and did not
      differ from those of healthy subjects at the follow-up evaluation. Akathisia was
      also reduced. In the patients receiving risperidone at baseline, basal ganglia
      volumes did not differ between those exhibiting good and poor response, and no
      significant volume changes were observed in subjects with poor risperidone
      response after the switch to olanzapine treatment. CONCLUSIONS: Olanzapine
      reversed putamen and globus pallidus enlargement induced by typical
      antipsychotics but did not alter volumes in patients previously treated with
      risperidone. Changes in striatal volumes related to typical and atypical
      antipsychotics may represent an interactive effect between individual medications
      and unique patient characteristics.

PMID- 15465981
TI  - Randomized, controlled, double-blind multicenter comparison of the efficacy and
      tolerability of ziprasidone and olanzapine in acutely ill inpatients with
      schizophrenia or schizoaffective disorder.
AB  - OBJECTIVE: Limited randomized, controlled trial data exist on possible
      differences between atypical antipsychotics in efficacy, overall tolerability,
      and important indices of health status. The authors compared the efficacy and
      tolerability of ziprasidone and olanzapine in the treatment of acutely ill
      inpatients with schizophrenia or schizoaffective disorder. METHOD: In this 6
      week, multicenter, double-blind, parallel-design, flexible-dose trial, patients
      were randomly assigned to receive ziprasidone (N=136) or olanzapine (N=133).
      Primary efficacy measures were improvement in Brief Psychiatric Rating Scale and
      Clinical Global Impression (CGI) severity scale scores; secondary measures were
      scores on the CGI improvement scale, Positive and Negative Syndrome Scale, and
      Calgary Depression Scale for Schizophrenia. Tolerability assessments included
      fasting lipid profiles, fasting glucose and insulin measurements,
      electrocardiography, and monitoring of vital signs and body weight. RESULTS: The
      overall mean daily doses were 129.9 mg (SD=27.3) for ziprasidone and 11.3 mg
      (SD=2.8) for olanzapine. Both antipsychotics were efficacious in improving
      symptoms and global illness severity. The two treatment groups did not differ
      significantly in primary or secondary efficacy measures at endpoint or in by
      visit analysis. Both agents were well tolerated. Body weight, total cholesterol,
      triglycerides, and low-density lipoprotein cholesterol significantly increased
      with olanzapine but not with ziprasidone; all between-group comparisons of these
      variables were significant and favored ziprasidone. Olanzapine, but not
      ziprasidone, was associated with significant increases in fasting insulin level.
      No patient in either group exhibited a corrected QT interval >/=500 msec.
      CONCLUSIONS: During 6 weeks' treatment, ziprasidone and olanzapine demonstrated
      comparable antipsychotic efficacy. Differences favoring ziprasidone were observed
      in metabolic parameters.

PMID- 15465982
TI  - Reduced spinophilin but not microtubule-associated protein 2 expression in the
      hippocampal formation in schizophrenia and mood disorders: molecular evidence for
      a pathology of dendritic spines.
AB  - OBJECTIVE: Aberrant synaptic connectivity may underlie the involvement of the
      hippocampus in schizophrenia. There is reasonable neuropathological evidence for
      a presynaptic pathology but few studies of the postsynaptic component. This study
      tested the hypothesis that hippocampal dendritic pathology is also present in
      schizophrenia. METHOD: Using in situ hybridization in sections of hippocampal
      formation from 10 patients with schizophrenia, 10 patients with mood disorders
      (three with bipolar disorder and seven with major depression), and 10 healthy
      comparison subjects, the authors examined the expression of two important
      dendritic genes: spinophilin, which serves as a marker of dendritic spines, and
      microtubule-associated protein 2 (MAP2), an overall dendritic marker. RESULTS:
      The patients with schizophrenia had lower levels of spinophilin mRNA in CA4
      (hilus), CA3, the subiculum, and the entorhinal cortex than did the normal
      comparison subjects. The mood disorder group showed similar differences from the
      comparison group. MAP2 and cyclophilin mRNA did not differ between the groups in
      any subfield. CONCLUSIONS: Decreased spinophilin but unchanged MAP2 expression
      provides molecular evidence for a hippocampal dendritic pathology in
      schizophrenia that preferentially affects the spines. As spines are the target of
      most glutamatergic synapses, the data extend the evidence that excitatory
      synapses are particularly affected. Similar dendritic spine pathology may also
      occur in mood disorders.

PMID- 15465983
TI  - Neurobiology of non-REM sleep in depression: further evidence for hypofrontality
      and thalamic dysregulation.
AB  - OBJECTIVE: Sleep disturbances characterize depression and may reflect the
      abnormal persistence of brain activity from wakefulness into non-REM sleep. The
      goal of this study was to investigate the functional neuroanatomical correlates
      of non-REM sleep relative to presleep wakefulness in depressed patients and
      healthy subjects. METHOD: Twelve medication-free depressed patients and 13
      healthy subjects underwent polysomnography and [(18)F]fluorodeoxyglucose positron
      emission tomography scans during presleep wakefulness and non-REM sleep.
      Statistical parametric mapping contrasts were performed to detect differences in
      relative regional cerebral glucose metabolism between presleep wakefulness and
      non-REM sleep in each group as well as interactions across states and between
      groups. RESULTS: Relative to healthy subjects, depressed patients showed less of
      a decrease in relative regional cerebral glucose metabolism from presleep
      wakefulness to non-REM sleep in the left and right laterodorsal frontal gyri,
      right medial prefrontal cortex, right superior and middle temporal gyri, insula,
      right posterior cingulate cortex, lingual gyrus, striate cortex, cerebellar
      vermis, and left thalamus. CONCLUSIONS: Patterns of relative regional cerebral
      glucose metabolism changes from presleep wakefulness to non-REM sleep differ in
      healthy subjects and depressed patients. Specifically, the transition from
      wakefulness to non-REM sleep was characterized by the relative persistence of
      elevated metabolic activity in frontoparietal regions and thalamus in depressed
      patients compared with healthy subjects. These findings suggest that abnormal
      thalamocortical network function may underlie sleep anomalies and complaints of
      nonrestorative sleep in depressed patients.

PMID- 15465984
TI  - Randomized, placebo-controlled trial of fluoxetine for acute treatment of minor
      depressive disorder.
AB  - OBJECTIVE: Minor depressive disorder is both common and associated with
      significant psychosocial impairment. This study examined antidepressant treatment
      efficacy in a large group of patients with minor depressive disorder. METHOD: One
      hundred sixty-two patients with minor depressive disorder were randomly assigned
      to receive fluoxetine or placebo in a 12-week, double-blind study; 73% (59 of 81)
      of the patients in each treatment group completed the study. Patients were
      evaluated weekly with standard depression rating instruments and measures of
      psychosocial impairment. Hypotheses were tested by last-observation-carried
      forward analysis of variance (ANOVA) and confirmed by mixed (random-effects)
      regression analysis. RESULTS: At baseline, minor depressive disorder patients
      were mildly to moderately depressed, with a corresponding degree of functional
      impairment. Over 12 weeks of treatment, both ANOVA and mixed regression showed
      fluoxetine to be superior to placebo as indicated by significantly greater
      improvement of fluoxetine-treated patients in scores on the 30-item clinician
      rated Inventory of Depressive Symptomatology, the 17-item and 21-item Hamilton
      Depression Rating Scale, the Beck Depression Inventory, and the Clinical Global
      Impression severity scale. Improvement in Global Assessment of Functioning Scale
      score was significantly greater for the fluoxetine group in mixed regression
      analysis only. Patients in both treatment groups reported a similar number and
      severity of adverse events during the 12-week treatment period. CONCLUSIONS:
      Clinicians frequently encounter minor depressive disorder either as a prodromal
      or residual phase of illness in major depressive disorder or as de novo minor
      depressive disorder episodes. Fluoxetine is significantly superior to placebo in
      reducing minor depressive disorder symptoms within a 12-week period. Improvement
      in psychosocial function with fluoxetine may take longer than 12 weeks.

PMID- 15465985
TI  - Six-year outcome of cognitive behavior therapy for prevention of recurrent
      depression.
AB  - OBJECTIVE: A paucity of studies use nonpharmacological strategies for preventing
      recurrence in depression. Cognitive behavior treatment of residual symptoms was
      found to yield a significantly lower relapse rate than clinical management in
      recurrent depression at a 2-year follow-up. The objective of this investigation
      was to provide a 6-year follow-up of cognitive behavior treatment versus clinical
      management. METHOD: Forty patients with recurrent major depression who had been
      successfully treated with antidepressant drugs were randomly assigned to either
      cognitive behavior treatment of residual symptoms (supplemented by lifestyle
      modification and well-being therapy) or clinical management. In both groups,
      antidepressant drugs were tapered and discontinued. A 6-year follow-up was
      undertaken. During this period, no antidepressant drugs were used unless a
      relapse ensued. RESULTS: Cognitive behavior treatment resulted in a significantly
      lower relapse rate (40%) at a 6-year follow-up than did clinical management
      (90%). When multiple recurrences were considered, the group that received
      cognitive behavior treatment had a significantly lower number of relapses in
      comparison with the clinical management group. CONCLUSIONS: The results suggest
      that the sequential use of cognitive behavior treatment after pharmacotherapy may
      improve the long-term outcome in recurrent depression. A significant proportion
      of patients with recurrent depression might be able to withdraw from medication
      successfully and to stay well for at least 6 years with a focused course of
      psychotherapy.

PMID- 15465986
TI  - Relationship of variability in residual symptoms with recurrence of major
      depressive disorder during maintenance treatment.
AB  - OBJECTIVE: To investigate how residual symptoms from an index episode of major
      depressive disorder may be associated with recurrence, the authors conducted a
      trial involving four maintenance treatment approaches and examined 1) whether the
      level and variability of residual symptoms differed among the maintenance
      treatment conditions and 2) whether greater symptom variability is associated
      with a higher likelihood of recurrence and more rapid recurrence. METHOD:
      Patients enrolled in a maintenance treatment study (N=114) were randomly assigned
      to one of four maintenance treatment conditions: imipramine plus interpersonal
      psychotherapy, imipramine alone, interpersonal psychotherapy alone, or no active
      treatment. Residual symptoms were characterized both as continuous variables
      (mean values and coefficients of variation for Hamilton Depression Rating Scale
      and Global Assessment Scale [GAS] scores) and as a categorical variable, the
      percentage of maintenance evaluations with a Hamilton depression scale score > or
      =8 (e.g., with a symptom peak). RESULTS: Analysis of variance revealed no
      differences among the four treatment conditions in patients' levels of residual
      symptoms or symptom variability assessed as a continuous variable, but patients
      in the combined treatment group had fewer symptom peaks, compared to those in the
      placebo and interpersonal psychotherapy groups. Cox proportional hazards modeling
      showed that higher coefficients of variation for both the Hamilton depression
      scale and the GAS scores and a greater percentage of evaluations with symptom
      peaks were associated with shorter survival times. CONCLUSIONS: A higher level of
      symptom variability during maintenance treatment is associated with higher risk
      for recurrence of depression and may provide a specific target for maintenance
      treatments.

PMID- 15465987
TI  - Effects of major depression on moment-in-time work performance.
AB  - OBJECTIVE: Although major depression is thought to have substantial negative
      effects on work performance, the possibility of recall bias limits self-report
      studies of these effects. The authors used the experience sampling method to
      address this problem by collecting comparative data on moment-in-time work
      performance among service workers who were depressed and those who were not
      depressed. METHOD: The group studied included 105 airline reservation agents and
      181 telephone customer service representatives selected from a larger baseline
      sample; depressed workers were deliberately oversampled. Respondents were given
      pagers and experience sampling method diaries for each day of the study. A
      computerized autodialer paged respondents at random time points. When paged,
      respondents reported on their work performance in the diary. Moment-in-time work
      performance was assessed at five random times each day over a 7-day data
      collection period (35 data points for each respondent). RESULTS: Seven conditions
      (allergies, arthritis, back pain, headaches, high blood pressure, asthma, and
      major depression) occurred often enough in this group of respondents to be
      studied. Major depression was the only condition significantly related to
      decrements in both of the dimensions of work performance assessed in the diaries:
      task focus and productivity. These effects were equivalent to approximately 2.3
      days absent because of sickness per depressed worker per month of being
      depressed. CONCLUSIONS: Previous studies based on days missed from work
      significantly underestimate the adverse economic effects associated with
      depression. Productivity losses related to depression appear to exceed the costs
      of effective treatment.

PMID- 15465988
TI  - Treatment outcome and physician-patient communication in primary care patients
      with chronic, recurrent depression.
AB  - OBJECTIVE: The authors' goal was to assess the adequacy of control, quality of
      life, and treatment experiences of patients with chronic, recurrent depression
      being treated by primary care physicians. METHOD: The sample comprised 1,001
      patients 18 years old or older who had chronic, recurring depression and were
      currently being treated with a single antidepressant prescribed by a primary care
      physician. These patients had responded positively to questions regarding the
      presence of clinical depression and prescription of a single antidepressant by a
      primary care physician during a telephone survey conducted in two stages
      separated by 18 to 24 months. The 1,001 patients participated in a structured, 20
      minute, anonymous interview conducted by trained personnel. RESULTS: Most
      patients had recurrent depression (median=5 episodes), and most had taken their
      current antidepressant for more than 1 year. The mean age at onset of depression
      was 33.8 years, and the mean age at time of diagnosis was 38.0 years, with
      treatment following a mean of 2 years later. Most patients were satisfied with
      the care they received from their primary care physician, but many also reported
      incomplete symptom resolution and substantial side effects from medications that
      were not discussed with or by their primary care physician. A majority of
      patients reported that treatment decisions were made in conjunction with their
      physician, a method that was preferred by three-quarters of the group. Although
      752 patients reported that they had mild or moderate depression, 729 were
      satisfied with their life and 600 said they were in good or excellent health.
      CONCLUSIONS: Despite being mostly satisfied with the care received from their
      primary care physician, patients with chronic, recurring depression had
      substantial levels of continuing dysfunction, distress, unrelieved symptoms, and
      medication side effects, which suggests several possible physician-centered,
      patient-centered, or system-centered barriers to treatment to full function and
      wellness.

PMID- 15465989
TI  - Phenomenology of rapid-cycling bipolar disorder: data from the first 500
      participants in the Systematic Treatment Enhancement Program.
AB  - OBJECTIVE: This study compared demographic and phenomenological variables between
      bipolar patients with and without rapid cycling as a function of bipolar I versus
      bipolar II status. METHOD: The authors examined demographic, historical, and
      symptomatic features of patients with and without rapid cycling in a cross
      sectional study of the first 500 patients with bipolar I or bipolar II disorder
      enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder, a
      multicenter project funded by the National Institute of Mental Health designed to
      evaluate the longitudinal outcome of patients with bipolar disorder. RESULTS:
      Rapid-cycling bipolar disorder occurred in 20% of the study group. Rapid-cycling
      patients were more likely to be women, although the effect was somewhat more
      pronounced among bipolar I patients than bipolar II patients. In addition, rapid
      cycling bipolar patients experienced onset of their illness at a younger age,
      were more often depressed at study entry, and had poorer global functioning in
      the year before study entry than nonrapid-cycling patients. Rapid-cycling
      patients also experienced a significantly greater number of depressive and
      hypomanic/manic episodes in the prior year. A lifetime history of psychosis did
      not distinguish between rapid and nonrapid-cycling patients, although bipolar I
      patients were more likely to have experienced psychosis than bipolar II patients.
      CONCLUSIONS: Patients with rapid-cycling bipolar disorder demonstrate a greater
      severity of illness than nonrapid-cycling patients on a number of clinical
      measures. This study highlights the need to refine treatments for rapid cycling
      to reduce the overall morbidity and mortality of patients with this illness
      course modifier.

PMID- 15465990
TI  - Actors' portrayals of depression to test interrater reliability in clinical
      trials.
AB  - OBJECTIVE: This study determined if actors could portray depressed patients to
      establish the interrater reliability of raters using the Hamilton Depression
      Rating Scale (HDRS). METHOD: Actors portrayed depressed patients using scripts
      derived from HDRS assessments obtained at three points during treatment. Four
      experienced raters blindly viewed videotapes of two patients and two actors. They
      guessed if each interviewee was a patient or an actor and rated the certainty of
      their guesses. For each interview, they also rated the realism of the portrayal
      and completed the HDRS. RESULTS: Experienced raters could not distinguish actors
      and patients better than chance and were equally certain of their right and wrong
      guesses. Actors and patients received high scores on the realism of their
      portrayals. The HDRS scores of the actor-patient pairs were correlated.
      CONCLUSIONS: Actors can effectively portray depressed patients. Future studies
      will determine if actors can accurately portray patients with anxiety and
      psychosis.

PMID- 15465991
TI  - Using a self-report depression scale to identify remission in depressed
      outpatients.
AB  - OBJECTIVE: Some have suggested that standardized rating scales be used in
      clinical practice to monitor the course of treatment; however, the time demands
      of clinical practice make it difficult to use such measures. This study derived a
      cutoff on a self-report depression questionnaire corresponding to the most widely
      used definition of remission (a score < or =7 on the 17-item Hamilton Depression
      Rating Scale). METHOD: Two hundred sixty-seven depressed outpatients were rated
      on the Hamilton depression scale and completed the Clinically Useful Depression
      Outcome Scale (CUDOS). The authors used receiver operating curve analysis to
      examine the ability of the CUDOS to identify remission on the Hamilton depression
      scale. RESULTS: A high level of agreement was found between the self-report and
      Hamilton depression scale assessments of remission. CONCLUSIONS: Self-report
      questionnaires represent a practical option for thoroughly and objectively
      evaluating the course of treatment and determining remission in depressed
      patients.

PMID- 15465992
TI  - Neuropsychological processing associated with recovery from depression after
      stereotactic subcaudate tractotomy.
AB  - OBJECTIVE: The authors compared patients who underwent stereotactic subcaudate
      tractotomy for depression, who were still depressed or recovered from depression,
      to identify therapeutic mechanisms. METHOD: Ten depressed and eight recovered
      psychosurgery patients, along with nine never-depressed subjects and nine who had
      recovered from depression with medication, completed the Iowa Gambling Task, a
      measure of decision making in the face of feedback. Psychosurgery patients also
      completed general neuropsychological testing. RESULTS: Recovered psychosurgery
      patients exhibited insensitivity to negative feedback on the Iowa Gambling Task
      compared to the other three groups. This difference between the groups remained
      when general neuropsychological performance was covaried out. CONCLUSIONS: These
      findings suggest acquired relative insensitivity to negative information as a
      specific mechanism mediating the antidepressant effect of stereotactic subcaudate
      tractotomy. Such insensitivity is not secondary to deficits in general
      neuropsychological functioning and is not a function of recovery from depression
      per se.

PMID- 15465993
TI  - Comparison of cortical 5-HT2A receptor binding in bulimia nervosa patients and
      healthy volunteers.
AB  - OBJECTIVE: Bulimia nervosa has been associated with alterations in central
      serotonergic (5-HT) function. This study investigated iodine-labeled 4-amino-N-[1
      [3-(4-fluorophenoxy) propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide
      ((123)I-5-I-R91150) binding to the 5-HT(2A) receptor in the brain by using single
      photon emission computed tomography in acutely ill bulimia nervosa patients.
      METHOD: Cortical (123)I-5-I-R91150 binding in 10 normal-weight patients with
      bulimia nervosa, purging type, was compared with that of 11 healthy volunteers.
      RESULTS: The 5-HT(2A) binding index of the bulimia nervosa patients, with and
      without correction for age, was not significantly different from that of the
      comparison group. CONCLUSIONS: As a group, acutely ill bulimia nervosa patients
      cannot be discriminated from healthy subjects on the basis of cortical (123)I-5-I
      R91150 binding to the 5-HT(2A) receptor.

PMID- 15465994
TI  - Volumetric neural correlates of antisaccade eye movements in first-episode
      psychosis.
AB  - OBJECTIVE: The authors investigated the structural brain correlates of
      antisaccade performance. METHOD: Magnetic resonance imaging was used to measure
      the volumes of the prefrontal, premotor, sensorimotor, and occipitoparietal
      cortices as well as the caudate, thalamus, cerebellar vermis, and cerebrum in 20
      first-episode psychosis patients and 18 healthy comparison subjects. Antisaccades
      were recorded by using infrared oculography. RESULTS: Groups significantly
      differed in terms of antisaccade error rate and amplitude gain and tended to
      differ in terms of latency but not brain region volumes. Premotor cortex volume
      predicted antisaccade error rate among comparison subjects. In the patient group,
      caudate volume was related to latency and amplitude gain. Negative symptoms,
      independent of structural volumes, predicted error rate. CONCLUSIONS: These
      findings point to altered structure-function relationships in first-episode
      psychosis.

PMID- 15465995
TI  - Omega-3 fatty acid treatment and T(2) whole brain relaxation times in bipolar
      disorder.
AB  - OBJECTIVE: The authors hypothesized that changes in brain membrane composition
      resulting from omega-3 fatty acid administration in patients with bipolar
      disorder would result in greater membrane fluidity, as detected by reductions in
      T(2) values. METHOD: Women with bipolar disorder (N=12) received omega-3 fatty
      acids for 4 weeks. A cohort of bipolar subjects (N=9) and a group without bipolar
      disorder (N=12) did not receive omega-3 fatty acids. T(2) values were acquired at
      baseline and after 4 weeks. RESULTS: Bipolar subjects who received omega-3 fatty
      acids had significant decreases in T(2). There was a dose-dependent effect when
      the bipolar omega-3 fatty acid group was subdivided into high- and low-dose
      cohorts. CONCLUSIONS: Omega-3 fatty acids lowered T(2) values, consistent with
      the hypothesis that the fluidity of cell membranes was altered. Further studies
      are needed to clarify the significance of alterations in brain physiology induced
      by omega-3 fatty acids, as reflected in T(2) values.

PMID- 15465996
TI  - Clozapine and typical antipsychotics.

PMID- 15465997
TI  - Prolactin elevation with ziprasidone.

PMID- 15465998
TI  - Aripiprazole for acute bipolar mania.

PMID- 15465999
TI  - Schizophrenia, syndrome X, and omega-3 fatty acids.

PMID- 15466000
TI  - The nature of traumatic memories.

PMID- 15466001
TI  - Typical versus atypical antipsychotics.

PMID- 15466002
TI  - Evidence-based promotion.

PMID- 15466003
TI  - POMGnT1 mutation and phenotypic spectrum in muscle-eye-brain disease.

PMID- 15466005
TI  - Tumour characteristics and prognosis of breast cancer patients carrying the
      germline CHEK2*1100delC variant.
AB  - BACKGROUND: The germline CHEK2*1100delC variant has been associated with breast
      cancer in multiple case families where involvement of BRCA1 and BRCA2 has been
      excluded. METHODS: We have investigated the tumour characteristics and prognosis
      of carriers of this germline variant by means of a prospective cohort study in an
      unselected cohort of 1084 consecutive patients with primary breast cancer. Data
      were collected for 34 patients with a germline CHEK2*1100delC mutation and for
      102 patients without this mutation, stratified by age and date of diagnosis of
      the first primary breast cancer (within 1 year). RESULTS: Carriers developed
      steroid receptor positive tumours (oestrogen receptor (ER): 91%; progesterone
      receptor (PR): 81%) more frequently than non-carriers (ER: 69%; PR: 53%; p =
      0.04). Mutation carriers more frequently had a female first or second degree
      relative with breast cancer (p = 0.03), or had any first or second degree
      relative with breast or ovarian cancer (p = 0.04). Patients with the CHEK2
      variant had a more unfavourable prognosis regarding the occurrence of
      contralateral breast cancer (relative risk (RR) = 5.74; 95% confidence interval
      (CI) 1.67 to 19.65), distant metastasis-free survival (RR = 2.81; 95% CI 1.20 to
      6.58), and disease-free survival (RR = 3.86; 95% CI 1.91 to 7.78). As yet, no
      difference with respect to overall survival has been found at a median follow up
      of 3.8 years. CONCLUSION: We conclude that carrying the CHEK2*1100delC mutation
      is an adverse prognostic indicator for breast cancer. If independently confirmed
      by others, intensive surveillance, and possibly preventive measures, should be
      considered for newly diagnosed breast cancer cases carrying the CHEK2*1100delC
      variant.

PMID- 15466006
TI  - Disruption of a new X linked gene highly expressed in brain in a family with two
      mentally retarded males.
AB  - BACKGROUND: Mental retardation (MR) affects 2-3% of the human population and some
      of these cases are genetically determined. Although several genes responsible for
      MR have been identified, many cases have still not been explained. METHODS: We
      have identified a pericentric inversion of the X chromosome inv(X)(p22.3;q13.2)
      segregating in a family where two male carriers have severe MR while female
      carriers are not affected. RESULTS: The molecular characterisation of this
      inversion led us to identify two new genes which are disrupted by the
      breakpoints: KIAA2022 in Xq13.2 and P2RY8 in Xp22.3. These genes were not
      previously fully characterised in humans. KIAA2022 encodes a protein which lacks
      significant homology to any other known protein and is highly expressed in the
      brain. P2RY8 is a member of the purine nucleotide G-protein coupled receptor gene
      family. It is located in the pseudo-autosomal region of the X chromosome and is
      not expressed in brain. CONCLUSIONS: Because the haploinsufficiency of P2RY8 in
      carrier mothers does not have a phenotypic consequence, we propose that the
      severe MR of the affected males in this family is due to the absence of the
      KIAA2022 gene product. However, screening 20 probands from X linked MR families
      did not reveal mutations in KIAA2022. Nonetheless, the high expression of this
      gene in fetal brain and in the adult cerebral cortex could be consistent with a
      role in brain development and/or cognitive function.

PMID- 15466007
TI  - A genome-wide linkage scan for bone mineral density in an extended sample:
      evidence for linkage on 11q23 and Xq27.
AB  - BACKGROUND: Osteoporosis is a major public health problem, mainly quantified by
      low bone mineral density (BMD). The majority of BMD variation is determined by
      genetic effects. A pilot whole genome linkage scan (WGS) was previously reported
      in 53 white pedigrees with 630 subjects. Several genomic regions were suggested
      to be linked to BMD variation. OBJECTIVE: To substantiate these previous findings
      and detect new genomic regions. METHODS: A WGS was conducted on an extended
      sample where the size was almost tripled (1816 subjects from 79 pedigrees). All
      the subjects were genotyped with 451 microsatellite markers spaced approximately
      8.1 cM apart across the human genome. Two point and multipoint linkage analyses
      were carried out using the variance component method. RESULTS: The strongest
      linkage signal was obtained on Xq27 with two point LOD scores of 4.30 for wrist
      BMD, and 2.57 for hip BMD, respectively. Another important region was 11q23,
      which achieved a maximum LOD score of 3.13 for spine BMD in multipoint analyses,
      confirming the results on this region in two earlier independent studies.
      Suggestive linkage evidence was also found on 7p14 and 20p12. CONCLUSIONS:
      Together with the findings from other studies, the current study has further
      delineated the genetic basis of bone mass and highlights the importance of
      increasing sample size to confirm linkage findings and to identify new regions of
      linkage.

PMID- 15466004
TI  - Recent advances in understanding haemochromatosis: a transition state.
AB  - Mutations in the hepcidin gene HAMP and the hemojuvelin gene HJV have recently
      been shown to result in juvenile haemochromatosis (JH). Hepcidin is an
      antimicrobial peptide that plays a key role in regulating intestinal iron
      absorption. Hepcidin levels are reduced in patients with haemochromatosis due to
      mutations in the HFE and HJV genes. Digenic inheritance of mutations in HFE and
      HAMP can result in either JH or hereditary haemochromatosis (HH) depending upon
      the severity of the mutation in HAMP. Here we review these findings and discuss
      how understanding the different types of haemochromatosis and our increasing
      knowledge of iron metabolism may help to elucidate the host's response to
      infection.

PMID- 15466008
TI  - Common variants at the PCOL2 and Sp1 binding sites of the COL1A1 gene and their
      interactive effect influence bone mineral density in Caucasians.
AB  - BACKGROUND: Osteoporosis, mainly characterised by low bone mineral density (BMD),
      is a serious public health problem. The collagen type I alpha 1 (COL1A1) gene is
      a prominent candidate gene for osteoporosis. Here, we examined whether genetic
      variants at the COL1A1 gene can influence BMD variation. METHODS: BMD was
      measured at nine skeletal sites in 313 Caucasian males and 308 Caucasian females.
      We screened four single nucleotide polymorphisms (SNPs) at the COL1A1 gene: PCOL2
      (-1997 G/T) in the promoter, Sp1 (1546 G/T) in the intron 1, Gly19Cys (3911 G/A)
      in exon 8, and Ala897Thr (13 773 G/A) in exon 45. Univariate and multivariate
      association approaches were used in the analyses. RESULTS: In multivariate
      analyses, we found a strong association between the PCOL2 SNP and BMD (p = 0.007
      to 0.024) and a suggestive association between the Sp1 SNP and BMD (p = 0.023 to
      0.048) in elderly Caucasian females. Interestingly, the interaction of these two
      SNPs was highly significantly associated with BMD variation (p = 0.001 to 0.003).
      The haplotype GG at the two SNPs had, on average, 2.7% higher BMD than non
      carriers (p = 0.006 to 0.026). CONCLUSIONS: Our data suggested that the common
      genetic variants at the PCOL2 and Sp1 sites, and importantly, their interactive
      effects, may contribute to BMD variation in elderly Caucasian females. Further
      studies are necessary to delineate the mechanisms underlying the effects of these
      common variants on BMD variation and to test their clinical relevance for general
      populations. In addition, our study highlighted the importance of multivariate
      analyses when multiple correlated phenotypes are under study.

PMID- 15466009
TI  - Genetic polymorphism of CYP1A2 increases the risk of myocardial infarction.
AB  - BACKGROUND: There is growing evidence that DNA damage caused by mutagens found in
      tobacco smoke may contribute to the development of coronary heart disease (CHD).
      In order to bind to DNA many mutagens require metabolic activation by cytochrome
      P450 (CYP) 1A1 or CYP1A2. The objective of this study was to determine the
      effects of CYP1A1 and CYP1A2 genotypes on risk of myocardial infarction (MI) and
      whether smoking interacts with genotype to modify risk. METHODS: Subjects (n =
      873) with a first acute non-fatal MI and population based controls (n = 932)
      living in Costa Rica, matched for age, sex, and area of residence, were genotyped
      for CYP1A1*2A and CYP1A2*1F by restriction-fragment length polymorphism (RFLP)
      PCR, and smoking status was determined by questionnaire. RESULTS: After adjusting
      for matching variables and potential confounders, no association was observed
      between CYP1A1 genotype and risk of MI. Compared to individuals with the high
      inducibility CYP1A2*1A/*1A genotype, the adjusted odds ratio and 95% confidence
      intervals for risk of MI were 1.19 (0.97 to 1.47) for the *1A/*1F genotype and
      1.55 (1.10 to 2.18) for the *1F/*1F genotype. No significant interactions were
      observed between smoking and either CYP1A1 or CYP1A2 genotype. CONCLUSIONS: The
      low inducibility genotype for CYP1A2 was associated with an increased risk of MI.
      This effect was independent of smoking status and suggests that a substrate of
      CYP1A2 that is detoxified rather than activated may play a role in CHD.

PMID- 15466010
TI  - Identification of novel MUNC13-4 mutations in familial haemophagocytic
      lymphohistiocytosis and functional analysis of MUNC13-4-deficient cytotoxic T
      lymphocytes.
AB  - BACKGROUND: Familial haemophagocytic lymphohistiocytosis (FHL) has an autosomal
      recessive mode of inheritance and consists of at least three subtypes. FHL2
      subtype with perforin (PRF1) mutation accounts for 30% of all FHL cases, while
      FHL with MUNC13-4 mutation was recently identified and designated as FHL3
      subtype. OBJECTIVE: To examine MUNC13-4 mutations and the cytotoxic function of
      MUNC13-4 deficient T lymphocytes in Japanese FHL patients METHODS: Mutations of
      MUNC13-4 and the cytotoxicity of MUNC13-4-deficient cytotoxic T lymphocytes (CTL)
      were analysed in 16 Japanese families with non-FHL2 subtype. RESULTS: Five new
      mutations of the MUNC13-4 gene were identified in six families. The mutations
      were in the introns 4, 9, and 18, and exons 8 and 19. Two families had homozygous
      mutations, while the remaining four had compound heterozygous mutations.
      Cytotoxicity of MUNC13-4 deficient CTL was low compared with control CTL, but was
      still present. Clinically, the onset of disease tended to occur late; moreover,
      natural killer cell activity was not deficient in some FHL3 patients.
      CONCLUSIONS: MUNC13-4 mutations play a role in the development of FHL3 through a
      defective cytotoxic pathway.

PMID- 15466011
TI  - Identification of the gene for Nance-Horan syndrome (NHS).
AB  - BACKGROUND: The disease intervals for Nance-Horan syndrome (NHS [MIM 302350]) and
      X linked congenital cataract (CXN) overlap on Xp22. OBJECTIVE: To identify the
      gene or genes responsible for these diseases. METHODS: Families with NHS were
      ascertained. The refined locus for CXN was used to focus the search for candidate
      genes, which were screened by polymerase chain reaction and direct sequencing of
      potential exons and intron-exon splice sites. Genomic structures and homologies
      were determined using bioinformatics. Expression studies were undertaken using
      specific exonic primers to amplify human fetal cDNA and mouse RNA. RESULTS: A
      novel gene NHS, with no known function, was identified as causative for NHS.
      Protein truncating mutations were detected in all three NHS pedigrees, but no
      mutation was identified in a CXN family, raising the possibility that NHS and CXN
      may not be allelic. The NHS gene forms a new gene family with a closely related
      novel gene NHS-Like1 (NHSL1). NHS and NHSL1 lie in paralogous duplicated
      chromosomal intervals on Xp22 and 6q24, and NHSL1 is more broadly expressed than
      NHS in human fetal tissues. CONCLUSIONS: This study reports the independent
      identification of the gene causative for Nance-Horan syndrome and extends the
      number of mutations identified.

PMID- 15466012
TI  - A new phenotype of recessively inherited foveal hypoplasia and anterior segment
      dysgenesis maps to a locus on chromosome 16q23.2-24.2.

PMID- 15466013
TI  - A novel PHF6 mutation results in enhanced exon skipping and mild Borjeson
      Forssman-Lehmann syndrome.

PMID- 15466014
TI  - Mutations of the mitochondrial ND1 gene as a cause of MELAS.

PMID- 15466015
TI  - Opposite effects of interleukin 10 common gene polymorphisms in cardiovascular
      diseases and in successful ageing: genetic background of male centenarians is
      protective against coronary heart disease.

PMID- 15466016
TI  - Large quantitative effect of melanocortin-4 receptor gene mutations on body mass
      index.

PMID- 15466017
TI  - Regulatory small RNAs: the key to coordinating global regulatory circuits.

PMID- 15466018
TI  - Control of membrane lipid fluidity by molecular thermosensors.

PMID- 15466019
TI  - MicC, a second small-RNA regulator of Omp protein expression in Escherichia coli.
AB  - In a previous bioinformatics-based search for novel small-RNA genes encoded by
      the Escherichia coli genome, we identified a region, IS063, located between the
      ompN and ydbK genes, that encodes an approximately 100-nucleotide small-RNA
      transcript. Here we show that the expression of this small RNA is increased at a
      low temperature and in minimal medium. Twenty-two nucleotides at the 5' end of
      this transcript have the potential to form base pairs with the leader sequence of
      the mRNA encoding the outer membrane protein OmpC. The deletion of IS063
      increased the expression of an ompC-luc translational fusion 1.5- to 2-fold, and
      a 10-fold overexpression of the small RNA led to a 2- to 3-fold repression of the
      fusion. Deletion and overexpression of the IS063 RNA also resulted in increases
      and decreases, respectively, in OmpC protein levels. Taken together, these
      results suggest that IS063 is a regulator of OmpC expression; thus, the small RNA
      has been renamed MicC. The antisense regulation was further demonstrated by the
      finding that micC mutations were suppressed by compensatory mutations in the ompC
      mRNA. MicC was also shown to inhibit ribosome binding to the ompC mRNA leader in
      vitro and to require the Hfq RNA chaperone for its function. We suggest that the
      MicF and MicC RNAs act in conjunction with the EnvZ-OmpR two-component system to
      control the OmpF/OmpC protein ratio in response to a variety of environmental
      stimuli.

PMID- 15466020
TI  - GadY, a small-RNA regulator of acid response genes in Escherichia coli.
AB  - A previous bioinformatics-based search for small RNAs in Escherichia coli
      identified a novel RNA named IS183. The gene encoding this small RNA is located
      between and on the opposite strand of genes encoding two transcriptional
      regulators of the acid response, gadX (yhiX) and gadW (yhiW). Given that IS183 is
      encoded in the gad gene cluster and because of its role in regulating acid
      response genes reported here, this RNA has been renamed GadY. We show that GadY
      exists in three forms, a long form consisting of 105 nucleotides and two
      processed forms, consisting of 90 and 59 nucleotides. The expression of this
      small RNA is highly induced during stationary phase in a manner that is dependent
      on the alternative sigma factor sigmaS. Overexpression of the three GadY RNA
      forms resulted in increased levels of the mRNA encoding the GadX transcriptional
      activator, which in turn caused increased levels of the GadA and GadB glutamate
      decarboxylases. A promoter mutation which abolished gadY expression resulted in a
      reduction in the amount of gadX mRNA during stationary phase. The gadY gene was
      shown to overlap the 3' end of the gadX gene, and this overlap region was found
      to be necessary for the GadY-dependent accumulation of gadX mRNA. We suggest that
      during stationary phase, GadY forms base pairs with the 3'-untranslated region of
      the gadX mRNA and confers increased stability, allowing for gadX mRNA
      accumulation and the increased expression of downstream acid resistance genes.

PMID- 15466021
TI  - Identification of a staphylococcal AgrB segment(s) responsible for group-specific
      processing of AgrD by gene swapping.
AB  - The four gene products of the accessory gene regulator (agr) P2 operon of
      Staphylococcus aureus assemble a quorum-sensing system: AgrA and AgrC resemble a
      two-component signal transduction system, and AgrB and AgrD are required to
      produce an autoinducing peptide. Upon activation, this quorum-sensing system
      positively regulates the transcription of the P2 operon as well as the P3 operon,
      whose transcript, RNAIII, regulates the expression of virulence genes. Four
      groups of S. aureus have been identified based on the agr sequences and the group
      specific interaction between the autoinducing peptide and AgrC. AgrB is a
      transmembrane protein involved in the processing of AgrD propeptide, and its
      interaction with AgrD is also group specific. In this study, a series of chimeric
      AgrBs were constructed by swapping between group I and group II AgrBs, and these
      mutants were used to analyze the group-specific segment(s) in AgrB that was
      responsible for AgrD processing. Our results revealed that the first
      transmembrane alpha-helix and the extracellular loop 1 of group I AgrB were
      decisive in the specific processing of group I AgrD. In contrast, two hydrophilic
      segments of group II AgrB played a crucial role in the group-specific processing
      of group II AgrD. We also found that several chimeric AgrBs were capable of
      processing AgrD from both groups, suggesting that all AgrB homologues may utilize
      the same or a similar mechanism in the processing of AgrDs.

PMID- 15466022
TI  - Global transcriptional effects of a suppressor tRNA and the inactivation of the
      regulator frmR.
AB  - Expression of an amber suppressor tRNA should result in read-through of the 326
      open reading frames (ORFs) that terminate with amber stop codons in the
      Escherichia coli genome, including six pseudogenes. Abnormal extension of an ORF
      might alter the activities of the protein and have effects on cellular
      physiology, while suppression of a pseudogene could lead to a gain of function.
      We used oligonucleotide microarrays to determine if any effects were apparent at
      the level of transcription in glucose minimal medium. Surprisingly, only eight
      genes had significantly different expression in the presence of the suppressor.
      Among these were the genes yaiN, adhC, and yaiM, forming a single putative operon
      whose likely function is the degradation of formaldehyde. Expression of wild-type
      yaiN was shown to result in repression of the operon, while a suppression
      mimicking allele lacking the amber stop codon and extended 7 amino acids did not.
      The operon was shown to be induced by formaldehyde, and the genes have been
      renamed frmR, frmA, and frmB, respectively.

PMID- 15466023
TI  - Flagellin from Listeria monocytogenes is glycosylated with beta-O-linked N
      acetylglucosamine.
AB  - Glycan staining of purified flagellin from Listeria monocytogenes serotypes 1/2a,
      1/2b, 1/2c, and 4b suggested that the flagellin protein from this organism is
      glycosylated. Mass spectrometry analysis demonstrated that the flagellin protein
      of L. monocytogenes is posttranslationally modified with O-linked N
      acetylglucosamine (GlcNAc) at up to six sites/monomer. The sites of glycosylation
      are all located in the central, surface-exposed region of the protein monomer.
      Immunoblotting with a monoclonal antibody specific for beta-O-linked GlcNAc
      confirmed that the linkage was in the beta configuration, this residue being a
      posttranslational modification commonly observed in eukaryote nuclear and
      cytoplasmic proteins.

PMID- 15466024
TI  - Murein (peptidoglycan) binding property of the essential cell division protein
      FtsN from Escherichia coli.
AB  - The binding of the essential cell division protein FtsN of Escherichia coli to
      the murein (peptidoglycan) sacculus was studied. Soluble truncated variants of
      FtsN, including the complete periplasmic part of the protein as well as a variant
      containing only the C-terminal 77 amino acids, did bind to purified murein
      sacculi isolated from wild-type cells. FtsN variants lacking this C-terminal
      region showed reduced or no binding to murein. Binding of FtsN was severely
      reduced when tested against sacculi isolated either from filamentous cells with
      blocked cell division or from chain-forming cells of a triple amidase mutant.
      Binding experiments with radioactively labeled murein digestion products revealed
      that the longer murein glycan strands (>25 disaccharide units) showed a specific
      affinity to FtsN, but neither muropeptides, peptides, nor short glycan fragments
      bound to FtsN. In vivo FtsN could be cross-linked to murein with the soluble
      disulfide bridge containing cross-linker DTSSP. Less FtsN, but similar amounts of
      OmpA, was cross-linked to murein of filamentous or of chain-forming cells
      compared to levels in wild-type cells. Expression of truncated FtsN variants in
      cells depleted in full-length FtsN revealed that the presence of the C-terminal
      murein-binding domain was not required for cell division under laboratory
      conditions. FtsN was present in 3,000 to 6,000 copies per cell in exponentially
      growing wild-type E. coli MC1061. We discuss the possibilities that the binding
      of FtsN to murein during cell division might either stabilize the septal region
      or might have a function unrelated to cell division.

PMID- 15466025
TI  - The Escherichia coli dnaN159 mutant displays altered DNA polymerase usage and
      chronic SOS induction.
AB  - The Escherichia coli beta sliding clamp, which is encoded by the dnaN gene, is
      reported to interact with a variety of proteins involved in different aspects of
      DNA metabolism. Recent findings indicate that many of these partner proteins
      interact with a common surface on the beta clamp, suggesting that competition
      between these partners for binding to the clamp might help to coordinate both the
      nature and order of the events that take place at a replication fork. The purpose
      of the experiments discussed in this report was to test a prediction of this
      model, namely, that a mutant beta clamp protein impaired for interactions with
      the replicative DNA polymerase (polymerase III [Pol III]) would likewise have
      impaired interactions with other partner proteins and hence would display
      pleiotropic phenotypes. Results discussed herein indicate that the dnaN159
      encoded mutant beta clamp protein (beta159) is impaired for interactions with the
      alpha catalytic subunit of Pol III. Moreover, the dnaN159 mutant strain displayed
      multiple replication and repair phenotypes, including sensitivity to UV light, an
      absolute dependence on the polymerase activity of Pol I for viability, enhanced
      Pol V-dependent mutagenesis, and altered induction of the global SOS response.
      Furthermore, epistasis analyses indicated that the UV sensitivity of the dnaN159
      mutant was suppressed by (not epistatic with) inactivation of Pol IV (dinB gene
      product). Taken together, these findings suggest that in the dnaN159 mutant, DNA
      polymerase usage, and hence DNA replication, repair, and translesion synthesis,
      are altered. These findings are discussed in terms of a model to describe how the
      beta clamp might help to coordinate protein traffic at the replication fork.

PMID- 15466026
TI  - Concerted effects of amino acid substitutions in conserved charged residues and
      other residues in the cytoplasmic domain of PomA, a stator component of Na+
      driven flagella.
AB  - PomA is a membrane protein that is one of the essential components of the sodium
      driven flagellar motor in Vibrio species. The cytoplasmic charged residues of
      Escherichia coli MotA, which is a PomA homolog, are believed to be required for
      the interaction of MotA with the C-terminal region of FliG. It was previously
      shown that a PomA variant with neutral substitutions in the conserved charged
      residues (R88A, K89A, E96Q, E97Q, and E99Q; AAQQQ) was functional. In the present
      study, five other conserved charged residues were replaced with neutral amino
      acids in the AAQQQ PomA protein. These additional substitutions did not affect
      the function of PomA. However, strains expressing the AAQQQ PomA variant with
      either an L131F or a T132M substitution, neither of which affected motor function
      alone, exhibited a temperature-sensitive (TS) motility phenotype. The double
      substitutions R88A or E96Q together with L131F were sufficient for the TS
      phenotype. The motility of the PomA TS mutants immediately ceased upon a
      temperature shift from 20 to 42 degrees C and was restored to the original level
      approximately 10 min after the temperature was returned to 20 degrees C. It is
      believed that PomA forms a channel complex with PomB. The complex formation of TS
      PomA and PomB did not seem to be affected by temperature. Suppressor mutations of
      the TS phenotype were mapped in the cytoplasmic boundaries of the transmembrane
      segments of PomA. We suggest that the cytoplasmic surface of PomA is changed by
      the amino acid substitutions and that the interaction of this surface with the
      FliG C-terminal region is temperature sensitive.

PMID- 15466027
TI  - Functional and structural analysis of HrcA repressor protein from Caulobacter
      crescentus.
AB  - A large number of bacteria regulate chaperone gene expression during heat shock
      by the HrcA-CIRCE system, in which the DNA element called CIRCE serves as binding
      site for the repressor protein HrcA under nonstress conditions. In Caulobacter
      crescentus, the groESL operon presents a dual type of control. Heat shock
      induction is controlled by a sigma32-dependent promoter and the HrcA-CIRCE system
      plays a role in regulation of groESL expression under physiological temperatures.
      To study the activity of HrcA in vitro, we purified a histidine-tagged version of
      the protein, and specific binding to the CIRCE element was obtained by gel shift
      assays. The amount of retarded DNA increased significantly in the presence of
      GroES/GroEL, suggesting that the GroE chaperonin machine modulates HrcA activity.
      Further evidence of this modulation was obtained using lacZ transcription fusions
      with the groESL regulatory region in C. crescentus cells, producing different
      amounts of GroES/GroEL. In addition, we identified the putative DNA-binding
      domain of HrcA through extensive protein sequence comparison and constructed
      various HrcA mutant proteins containing single amino acid substitutions in or
      near this region. In vitro and in vivo experiments with these mutated proteins
      indicated several amino acids important for repressor activity.

PMID- 15466029
TI  - Modulation of monomer conformation of the BglG transcriptional antiterminator
      from Escherichia coli.
AB  - The BglG protein positively regulates expression of the bgl operon in Escherichia
      coli by binding as a dimer to the bgl transcript and preventing premature
      termination of transcription in the presence of beta-glucosides. BglG activity is
      negatively controlled by BglF, the beta-glucoside phosphotransferase, which
      reversibly phosphorylates BglG according to beta-glucoside availability, thus
      modulating its dimeric state. BglG consists of an RNA-binding domain and two
      homologous domains, PRD1 and PRD2. Based on structural studies of a BglG
      homologue, the two PRDs fold similarly, and the interactions within the dimer are
      PRD1-PRD1 and PRD2-PRD2. We have recently shown that the affinity between PRD1
      and PRD2 of BglG is high, and a fraction of the BglG monomers folds in the cell
      into a compact conformation, in which PRD1 and PRD2 are in close proximity. We
      show here that both BglG forms, the compact and noncompact, bind to the active
      site-containing domain of BglF, IIB(bgl), in vitro. The interaction of BglG with
      IIB(bgl) or BglF is mediated by PRD2. Both BglG forms are detected as
      phosphorylated proteins after in vitro phosphorylation with IIB(bgl) and are
      dephosphorylated by BglF in vitro in the presence of beta-glucosides.
      Nevertheless, genetic evidence indicates that the interaction of IIB(bgl) and
      BglF with the compact form is seemingly less favorable. Using in vivo cross
      linking, we show that BglF enhances folding of BglG into a compact conformation,
      whereas the addition of beta-glucosides reduces the amount of this form. Based on
      these results we suggest a model for the modulation of BglG conformation and
      activity by BglF.

PMID- 15466028
TI  - FtsZ collaborates with penicillin binding proteins to generate bacterial cell
      shape in Escherichia coli.
AB  - The mechanisms by which bacteria adopt and maintain individual shapes remain
      enigmatic. Outstanding questions include why cells are a certain size, length,
      and width; why they are uniform or irregular; and why some branch while others do
      not. Previously, we showed that Escherichia coli mutants lacking multiple
      penicillin binding proteins (PBPs) display extensive morphological diversity.
      Because defective sites in these cells exhibit the structural and functional
      characteristics of improperly localized poles, we investigated the connection
      between cell division and shape. Here we show that under semipermissive
      conditions the temperature-sensitive FtsZ84 protein produces branched and
      aberrant cells at a high frequency in mutants lacking PBP 5, and this phenotype
      is exacerbated by the loss of additional peptidoglycan endopeptidases.
      Surprisingly, certain ftsZ84 strains lyse at the nonpermissive temperature
      instead of filamenting, and inhibition of wild-type FtsZ forces some mutants into
      tightly wound spirillum-like morphologies. The results demonstrate that
      significant aspects of bacterial shape are dictated by a previously unrecognized
      relationship between the septation machinery and ostensibly minor peptidoglycan
      modifying enzymes and that under certain circumstances improper FtsZ function can
      destroy the structural integrity of the cell.

PMID- 15466031
TI  - Methylation of GPLs in Mycobacterium smegmatis and Mycobacterium avium.
AB  - Several species of mycobacteria express abundant glycopeptidolipids (GPLs) on the
      surfaces of their cells. The GPLs are glycolipids that contain modified sugars
      including acetylated 6-deoxy-talose and methylated rhamnose. Four
      methyltransferases have been implicated in the synthesis of the GPLs of
      Mycobacterium smegmatis and Mycobacterium avium. A rhamnosyl 3-O-methytransferase
      and a fatty acid methyltransferase of M. smegmatis have been previously
      characterized. In this paper, we characterize the methyltransferases that are
      responsible for modifying the hydroxyl groups at positions 2 and 4 of rhamnose
      and propose the biosynthetic sequence of GPL trimethylrhamnose formation. The
      analysis of M. avium genes through the creation of specific mutants is
      technically difficult; therefore, an alternative approach to determine the
      function of putative methyltransferases of M. avium was undertaken.
      Complementation of M. smegmatis methyltransferase mutants with M. avium genes
      revealed that MtfC and MtfB of the latter species have 4-O-methyltransferase
      activity and that MtfD is a 3-O-methyltransferase which can modify rhamnose of
      GPLs in M. smegmatis.

PMID- 15466030
TI  - PAS domain of the Aer redox sensor requires C-terminal residues for native-fold
      formation and flavin adenine dinucleotide binding.
AB  - The Aer protein in Escherichia coli is a membrane-bound, FAD-containing aerotaxis
      and energy sensor that putatively monitors the redox state of the electron
      transport system. Binding of FAD to Aer requires the N-terminal PAS domain and
      residues in the F1 region and C-terminal HAMP domain. The PAS domains of other
      PAS proteins are soluble in water. To investigate properties of the PAS domain,
      we subcloned segments of the aer gene from E. coli that encode the PAS domain
      with and without His6 tags and expressed the PAS peptides in E. coli. The 20-kDa
      His6-Aer2-166 PAS-F1 fragment was purified as an 800-kDa complex by gel
      filtration chromatography, and the associating protein was identified by N
      terminal sequencing as the chaperone protein GroEL. None of the N-terminal
      fragments of Aer found in the soluble fraction was released from GroEL,
      suggesting that these peptides do not fold correctly in an aqueous environment
      and require a motif external to the PAS domain for proper folding. Consistent
      with this model, peptide fragments that included the membrane binding region and
      part (Aer2-231) or all (Aer2-285) of the HAMP domain inserted into the membrane,
      indicating that they were released by GroEL. Aer2-285, but not Aer2-231, bound
      FAD, confirming the requirement for the HAMP domain in stabilizing FAD binding.
      The results raise an interesting possibility that residues outside the PAS domain
      that are required for FAD binding are essential for formation of the PAS native
      fold.

PMID- 15466032
TI  - The glutathione-glutaredoxin system in Rhodobacter capsulatus: part of a complex
      regulatory network controlling defense against oxidative stress.
AB  - Mutants with defects in components of the glutathione-glutaredoxin (GSH/Grx)
      system of Rhodobacter capsulatus were constructed to study its role in defense
      against oxidative stress and the redox-dependent formation of photosynthetic
      complexes. The lack of the glutaredoxin 3 gene (grxC) or the glutathione
      synthetase B gene (gshB) resulted in lower growth rates under aerobic conditions
      and higher sensitivity to oxidative stress, confirming the role of the GSH/Grx
      system in oxidative stress defense. Both mutants are highly sensitive to
      disulfide stress, indicating a major contribution of the GSH/Grx system to the
      thiol-disulfide redox buffer in the cytoplasm. Like mutations in the thioredoxin
      system, mutations in the GSH/Grx system affected the formation of photosynthetic
      complexes, which is redox dependent in R. capsulatus. Expression of the genes
      grxC, gshB, grxA for glutaredoxin 1, and gorA for glutathione reductase, all
      encoding components of the GSH/Grx system, was not induced by oxidative stress.
      Other genes, for which a role in oxidative stress was established in Escherichia
      coli, acnA, fpr, fur, and katG, were strongly induced by oxidative stress in R.
      capsulatus. Mutations in the grxC, and/or gshB, and/or trxC (thioredoxin 2) genes
      affected expression of these genes, indicating an interplay of the different
      defense systems against oxidative stress. The OxyR and the SoxRS regulons control
      the expression of many genes involved in oxidative stress defense in E. coli in
      response to H2O2 and superoxide, respectively. Our data and the available genome
      sequence of R. capsulatus suggest that a SoxRS system is lacking but an
      alternative superoxide specific regulator exists in R. capsulatus. While the
      expression of gorA and grxA is regulated by H2O2 in E. coli this is not the case
      in R. capsulatus, indicating that the OxyR regulons of these two species are
      significantly different.

PMID- 15466033
TI  - Effect of bile on the cell surface permeability barrier and efflux system of
      Vibrio cholerae.
AB  - Gram-negative bacteria are inherently impermeable to hydrophobic compounds, due
      to the synergistic activity of the permeability barrier imposed by the outer
      membrane and energy dependent efflux systems. The gram-negative, enteric pathogen
      Vibrio cholerae appears to be deficient in both these activities; the outer
      membrane is not an effective barrier to hydrophobic permeants, presumably due to
      the presence of exposed phospholipids on the outer leaflet of the outer membrane,
      and efflux systems are at best only partially active. When V. cholerae was grown
      in the presence of bile, entry of hydrophobic compounds into the cells was
      significantly reduced. No difference was detected in the extent of exposed
      phospholipids on the outer leaflet of the outer membrane between cells grown in
      the presence or absence of bile. However, in the presence of energy uncouplers,
      uptake of hydrophobic probes was comparable between cells grown in the presence
      or absence of bile, indicating that energy-dependent efflux processes may be
      involved in restricting the entry of hydrophobic permeants into bile grown cells.
      Indeed, an efflux system(s) is essential for survival of V. cholerae in the
      presence of bile. Expression of acrAB, encoding an RND family efflux pump, was
      significantly increased in V. cholerae cells grown in vitro in the presence of
      bile and also in cells grown in rabbit intestine.

PMID- 15466034
TI  - Transcriptional regulation of the ant operon, encoding two-component anthranilate
      1,2-dioxygenase, on the carbazole-degradative plasmid pCAR1 of Pseudomonas
      resinovorans strain CA10.
AB  - The carbazole-degradative plasmid pCAR1 of Pseudomonas resinovorans strain CA10
      has two gene clusters, carAaAaBaBbCAcAdDFE and antABC, which are involved in the
      conversions of carbazole to anthranilate and anthranilate to catechol,
      respectively. We proved that the antABC gene cluster, encoding two-component
      anthranilate 1,2-dioxygenase, constitutes a single transcriptional unit through
      Northern hybridization and reverse transcription-PCR (RT-PCR) analyses. The
      transcription start point of antA was mapped at 53 bp upstream point of its
      translation start point, and the -10 and -35 boxes were homologous to conserved
      sigma70 recognition sequence. Hence the promoter of the ant operon was designated
      Pant. 5' Deletion analyses using luciferase as a reporter showed that the region
      up to at least 70 bp from the transcription start point of antA was necessary for
      the activation of Pant. Luciferase expression from Pant was induced by
      anthranilate itself, but not by catechol. Two probable AraC/XylS-type regulatory
      genes found on pCAR1, open reading frame 22 (ORF22) and ORF23, are tandemly
      located 3.2 kb upstream of the antA gene. We revealed that the product of ORF23,
      designated AntR, is indispensable for the stimulation of Pant in Pseudomonas
      putida cells. Northern hybridization and RT-PCR analyses revealed that another
      copy of Pant, which is thought to be translocated about 2.1 kb upstream of the
      carAa gene as a consequence of the transposition of ISPre1, actually drives
      transcription of the carAa gene in the presence of anthranilate, indicating that
      both ant and car operons are simultaneously regulated by AntR.

PMID- 15466035
TI  - Replicon-specific regulation of small heat shock genes in Agrobacterium
      tumefaciens.
AB  - Four genes coding for small heat shock proteins (sHsps) were identified in the
      genome sequence of Agrobacterium tumefaciens, one on the circular chromosome
      (hspC), one on the linear chromosome (hspL), and two on the pAT plasmid (hspAT1
      and hspAT2). Induction of sHsps at elevated temperatures was revealed by
      immunoblot analyses. Primer extension experiments and translational lacZ fusions
      demonstrated that expression of the pAT-derived genes and hspL is controlled by
      temperature in a regulon-specific manner. While the sHsp gene on the linear
      chromosome turned out to be regulated by RpoH (sigma32), both copies on pAT were
      under the control of highly conserved ROSE (named for repression of heat shock
      gene expression) sequences in their 5' untranslated region. Secondary structure
      predictions of the corresponding mRNA strongly suggest that it represses
      translation at low temperatures by masking the Shine-Dalgarno sequence. The hspC
      gene was barely expressed (if at all) and not temperature responsive.

PMID- 15466036
TI  - Phosphorylation and RsbX-dependent dephosphorylation of RsbR in the RsbR-RsbS
      complex of Bacillus subtilis.
AB  - In the pathway that controls sigmaB activity, the RsbR-RsbS complex plays an
      important role by trapping RsbT, a positive regulator of sigmaB of Bacillus
      subtilis. We have proposed that at the onset of stress, RsbR becomes
      phosphorylated, resulting in an enhanced activity of RsbT towards RsbS. RsbT is
      then free to interact with and activate RsbU, which in turn ultimately activates
      sigmaB. In this study with purified proteins, we used mutant RsbR proteins to
      analyze the role of its phosphorylatable threonine residues. The results show
      that the phosphorylation of either of the two RsbT-phosphorylatable threonine
      residues (T171 and T205) in RsbR enhanced the kinase activity of RsbT towards
      RsbS. However, it appeared that RsbT preferentially phosphorylates T171. We also
      present in vitro evidence that identifies RsbX as a potential phosphatase for
      RsbR T205.

PMID- 15466037
TI  - The transcriptional regulator AlgR controls cyanide production in Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic lung
      infections in cystic fibrosis (CF) patients. One characteristic of P. aeruginosa
      CF isolates is the overproduction of the exopolysaccharide alginate, controlled
      by AlgR. Transcriptional profiling analyses comparing mucoid P. aeruginosa
      strains to their isogenic algR deletion strains showed that the transcription of
      cyanide-synthesizing genes (hcnAB) was approximately 3-fold lower in the algR
      mutants. S1 nuclease protection assays corroborated these findings, indicating
      that AlgR activates hcnA transcription in mucoid P. aeruginosa. Quantification of
      hydrogen cyanide (HCN) production from laboratory isolates revealed that mucoid
      laboratory strains made sevenfold more HCN than their nonmucoid parental strains.
      In addition, comparison of laboratory and clinically derived nonmucoid strains
      revealed that HCN was fivefold higher in the nonmucoid CF isolates. Moreover, the
      average amount of cyanide produced by mucoid clinical isolates was 4.7 +/- 0.85
      micromol of HCN/mg of protein versus 2.4 +/- 0.40 micromol of HCN/mg of protein
      for nonmucoid strains from a survey conducted with 41 P. aeruginosa CF isolates
      from 24 patients. Our data indicate that (i) mucoid P. aeruginosa regardless of
      their origin (laboratory or clinically derived) produce more cyanide than their
      nonmucoid counterparts, (ii) AlgR regulates HCN production in P. aeruginosa, and
      (iii) P. aeruginosa CF isolates are more hypercyanogenic than nonmucoid
      laboratory strains. Taken together, cyanide production may be a relevant
      virulence factor in CF lung disease, the production of which is regulated, in
      part, by AlgR.

PMID- 15466038
TI  - Identification of a reactivating factor for adenosylcobalamin-dependent
      ethanolamine ammonia lyase.
AB  - The holoenzyme of adenosylcobalamin-dependent ethanolamine ammonia lyase
      undergoes suicidal inactivation during catalysis as well as inactivation in the
      absence of substrate. The inactivation involves the irreversible cleavage of the
      Co-C bond of the coenzyme. We found that the inactivated holoenzyme undergoes
      rapid and continuous reactivation in the presence of ATP, Mg2+, and free
      adenosylcobalamin in permeabilized cells (in situ), homogenate, and cell extracts
      of Escherichia coli. The reactivation was observed in the permeabilized E. coli
      cells carrying a plasmid containing the E. coli eut operon as well. From
      coexpression experiments, it was demonstrated that the eutA gene, adjacent to the
      5' end of ethanolamine ammonia lyase genes (eutBC), is essential for
      reactivation. It encodes a polypeptide consisting of 467 amino acid residues with
      predicted molecular weight of 49,599. No evidence was obtained that shows the
      presence of the auxiliary protein(s) potentiating the reactivation or associating
      with EutA. It was demonstrated with purified recombinant EutA that both the
      suicidally inactivated and O2-inactivated holoethanolamine ammonia lyase
      underwent rapid reactivation in vitro by EutA in the presence of
      adenosylcobalamin, ATP, and Mg2+. The inactive enzyme-cyanocobalamin complex was
      also activated in situ and in vitro by EutA under the same conditions. Thus, it
      was concluded that EutA is the only component of the reactivating factor for
      ethanolamine ammonia lyase and that reactivation and activation occur through the
      exchange of modified coenzyme for free intact adenosylcobalamin.

PMID- 15466039
TI  - Thermophilic, reversible gamma-resorcylate decarboxylase from Rhizobium sp.
      strain MTP-10005: purification, molecular characterization, and expression.
AB  - We found the occurrence of thermophilic reversible gamma-resorcylate
      decarboxylase (gamma-RDC) in the cell extract of a bacterium isolated from
      natural water, Rhizobium sp. strain MTP-10005, and purified the enzyme to
      homogeneity. The molecular mass of the enzyme was determined to be about 151 kDa
      by gel filtration, and that of the subunit was 37.5 kDa by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis; in other words, the enzyme was a
      homotetramer. The enzyme was induced specifically by the addition of gamma
      resorcylate to the medium. The enzyme required no coenzyme and did not act on 2,4
      dihydroxybenzoate, 2,5-dihydroxybenzoate, 3,4-dihydroxybenzoate, 3,5
      dihydroxybenzoate, 2-hydroxybenzoate, or 3-hydroxybenzoate. It was relatively
      thermostable to heat treatment, and its half-life at 50 degrees C was estimated
      to be 122 min; furthermore, it catalyzed the reverse carboxylation of resorcinol.
      The values of k(cat)/K(m) (mMu(-1) . s(-1)) for gamma-resorcylate and resorcinol
      at 30 degrees C and pH 7 were 13.4 and 0.098, respectively. The enzyme contains
      327 amino acid residues, and sequence identities were found with those of
      hypothetical protein AGR C 4595p from Agrobacterium tumefaciens strain C58 (96%
      identity), 5-carboxyvanillate decarboxylase from Sphingomonas paucimobilis (32%),
      and 2-amino-3-carboxymuconate-6-semialdehyde decarboxylases from Bacillus cereus
      ATCC 10987 (26%), Rattus norvegicus (26%), and Homo sapiens (25%). The genes
      (graA [1,230 bp], graB [888 bp], and graC [1,056 bp]) that are homologous to
      those in the resorcinol pathway also exist upstream and downstream of the gamma
      RDC gene. Judging from these results, the resorcinol pathway also exists in
      Rhizobium sp. strain MTP-10005, and gamma-RDC probably catalyzes a reaction just
      before the hydroxylase in it does.

PMID- 15466040
TI  - Isolation and characterization of ribosomes and translation initiation factors
      from the gram-positive soil bacterium Streptomyces lividans.
AB  - A primer extension inhibition (toeprint) assay was developed using ribosomes and
      ribosomal subunits from Streptomyces lividans. This assay allowed the study of
      ribosome binding to streptomycete leaderless and leadered mRNA. Purified 30S
      subunits were unable to form a ternary complex on aph leaderless mRNA, whereas
      70S ribosomes could form ternary complexes on this mRNA. 30S subunits formed
      ternary complexes on leadered aph and malE mRNA. The translation initiation
      factors (IF1, IF2, and IF3) from S. lividans were isolated and included in
      toeprint and filter binding assays with leadered and leaderless mRNA. Generally,
      the IFs reduced the toeprint signal on leadered mRNA; however, incubation of IF1
      and IF2 with 30S subunits that had been washed under high-salt conditions
      promoted the formation of a ternary complex on aph leaderless mRNA. Our data
      suggest that, as reported for Escherichia coli, initiation complexes with
      leaderless mRNAs might use a novel pathway involving 70S ribosomes or 30S
      subunits bound by IF1 and IF2 but not IF3. Some mRNA-ribosome-initiator tRNA
      reactions that yielded weak or no toeprint signals still formed complexes in
      filter binding assays, suggesting the occurrence of interactions that are not
      stable in the toeprint assay.

PMID- 15466041
TI  - Isolation, free-living capacities, and genome structure of "Candidatus
      Glomeribacter gigasporarum," the endocellular bacterium of the mycorrhizal fungus
      Gigaspora margarita.
AB  - "Candidatus Glomeribacter gigasporarum" is an endocellular beta-proteobacterium
      present in the arbuscular mycorrhizal (AM) fungus Gigaspora margarita. We
      established a protocol to isolate "Ca. Glomeribacter gigasporarum" from its host
      which allowed us to carry out morphological, physiological, and genomic
      investigations on purified bacteria. They are rod shaped, with a cell wall
      typical of gram-negative bacteria and a cytoplasm rich in ribosomes, and they
      present no flagella or pili. Isolated bacteria could not be grown in any of the
      19 culture media tested, but they could be kept alive for up to 4 weeks. PCR
      based investigations of purified DNA from isolated bacteria did not confirm the
      presence of all genes previously assigned to "Ca. Glomeribacter gigasporarum." In
      particular, the presence of nif genes could not be detected. Pulsed-field gel
      electrophoresis analyses allowed us to estimate the genome size of "Ca.
      Glomeribacter gigasporarum" to approximately 1.4 Mb with a ca. 750-kb chromosome
      and a 600- to 650-kb plasmid. This is the smallest genome known for a beta
      proteobacterium. Such small genome sizes are typically found in endocellular
      bacteria living permanently in their host. Altogether, our data suggest that "Ca.
      Glomeribacter gigasporarum" is an ancient obligate endocellular bacterium of the
      AM fungus G. margarita.

PMID- 15466042
TI  - A pH-sensitive function and phenotype: evidence that EutH facilitates diffusion
      of uncharged ethanolamine in Salmonella enterica.
AB  - The eutH gene is part of an operon that allows Salmonella enterica to use
      ethanolamine as a sole source of nitrogen, carbon, and energy. Although the
      sequence of EutH suggests a role in transport, eutH mutants use ethanolamine
      normally under standard conditions (pH 7.0). These mutants fail to use
      ethanolamine at a low pH. Evidence is presented that protonated ethanolamine
      (Eth0) does not enter cells, while uncharged ethanolamine (Eth0) diffuses freely
      across the membrane. The external concentration of Eth0 varies with the pH
      (pK=9.5). At pH 7.0, the standard ethanolamine concentration (41 mM) provides
      enough Eth0 for an influx rate that can support growth with or without EutH. When
      a lowered pH and/or ethanolamine concentration reduced the Eth0 concentration
      below 25 microM, EutH was needed to facilitate diffusion. EutH+ cells grew
      normally at Eth0 concentrations above 3 microM, close to the Km (9 microM) of the
      first degradative enzyme, ethanolamine ammonia lyase. It is suggested that EutH
      facilitates diffusion of Eth0. As predicted for a transporter, EutH contributed
      to the toxicity of ethanolamine seen under some conditions; furthermore, fusion
      of EutH to fluorescent Yfp protein provided evidence that EutH is a membrane
      protein.

PMID- 15466043
TI  - Chemical structure, conjugation, and cross-reactivity of Bacillus pumilus Sh18
      cell wall polysaccharide.
AB  - Bacillus pumilus strain Sh18 cell wall polysaccharide (CWP), cross-reactive with
      the capsular polysaccharide of Haemophilus influenzae type b, was purified and
      its chemical structure was elucidated using fast atom bombardment mass
      spectrometry, nuclear magnetic resonance techniques, and sugar-specific
      degradation procedures. Two major structures, 1,5-poly(ribitol phosphate) and 1,3
      poly(glycerol phosphate), with the latter partially substituted by 2-acetamido-2
      deoxy-alpha-galactopyranose (13%) and 2-acetamido-2-deoxy-alpha-glucopyranose
      (6%) on position O-2, were found. A minor component was established to be a
      polymer of -->3-O-(2-acetamido-2-deoxy-beta-glucopyranosyl)-1-->4-ribitol-1-OPO3-
      >. The ratios of the three components were 56, 34, and 10 mol%, respectively. The
      Sh18 CWP was covalently bound to carrier proteins, and the immunogenicity of the
      resulting conjugates was evaluated in mice. Two methods of conjugation were
      compared: (i) binding of 1-cyano-4-dimethylaminopyridinium tetrafluoroborate
      activated hydroxyl groups of the CWP to adipic acid dihydrazide (ADH)-derivatized
      protein, and (ii) binding of the carbodiimide-activated terminal phosphate group
      of the CWP to ADH-derivatized protein. The conjugate-induced antibodies reacted
      in an enzyme-linked immunosorbent assay with the homologous polysaccharide and
      with a number of other bacterial polysaccharides containing ribitol and glycerol
      phosphates, including H. influenzae types a and b and strains of Staphylococcus
      aureus and Staphylococcus epidermidis.

PMID- 15466044
TI  - Three parallel quorum-sensing systems regulate gene expression in Vibrio harveyi.
AB  - In a process called quorum sensing, bacteria communicate using extracellular
      signal molecules termed autoinducers. Two parallel quorum-sensing systems have
      been identified in the marine bacterium Vibrio harveyi. System 1 consists of the
      LuxM-dependent autoinducer HAI-1 and the HAI-1 sensor, LuxN. System 2 consists of
      the LuxS-dependent autoinducer AI-2 and the AI-2 detector, LuxPQ. The related
      bacterium, Vibrio cholerae, a human pathogen, possesses System 2 (LuxS, AI-2, and
      LuxPQ) but does not have obvious homologues of V. harveyi System 1. Rather,
      System 1 of V. cholerae is made up of the CqsA-dependent autoinducer CAI-1 and a
      sensor called CqsS. Using a V. cholerae CAI-1 reporter strain we show that many
      other marine bacteria, including V. harveyi, produce CAI-1 activity. Genetic
      analysis of V. harveyi reveals cqsA and cqsS, and phenotypic analysis of V.
      harveyi cqsA and cqsS mutants shows that these functions comprise a third V.
      harveyi quorum-sensing system that acts in parallel to Systems 1 and 2. Together
      these communication systems act as a three-way coincidence detector in the
      regulation of a variety of genes, including those responsible for
      bioluminescence, type III secretion, and metalloprotease production.

PMID- 15466045
TI  - Crystal structures of Escherichia coli ATP-dependent glucokinase and its complex
      with glucose.
AB  - Intracellular glucose in Escherichia coli cells imported by phosphoenolpyruvate
      dependent phosphotransferase system-independent uptake is phosphorylated by
      glucokinase by using ATP to yield glucose-6-phosphate. Glucokinases (EC 2.7.1.2)
      are functionally distinct from hexokinases (EC 2.7.1.1) with respect to their
      narrow specificity for glucose as a substrate. While structural information is
      available for ADP-dependent glucokinases from Archaea, no structural information
      exists for the large sequence family of eubacterial ATP-dependent glucokinases.
      Here we report the first structure determination of a microbial ATP-dependent
      glucokinase, that from E. coli O157:H7. The crystal structure of E. coli
      glucokinase has been determined to a 2.3-A resolution (apo form) and refined to
      final Rwork/Rfree factors of 0.200/0.271 and to 2.2-A resolution (glucose
      complex) with final Rwork/Rfree factors of 0.193/0.265. E. coli GlK is a
      homodimer of 321 amino acid residues. Each monomer folds into two domains, a
      small alpha/beta domain (residues 2 to 110 and 301 to 321) and a larger
      alpha+beta domain (residues 111 to 300). The active site is situated in a deep
      cleft between the two domains. E. coli GlK is structurally similar to
      Saccharomyces cerevisiae hexokinase and human brain hexokinase I but is distinct
      from the ADP-dependent GlKs. Bound glucose forms hydrogen bonds with the residues
      Asn99, Asp100, Glu157, His160, and Glu187, all of which, except His160, are
      structurally conserved in human hexokinase 1. Glucose binding results in a
      closure of the small domains, with a maximal Calpha shift of approximately 10 A.
      A catalytic mechanism is proposed that is consistent with Asp100 functioning as
      the general base, abstracting a proton from the O6 hydroxyl of glucose, followed
      by nucleophilic attack at the gamma-phosphoryl group of ATP, yielding glucose-6
      phosphate as the product.

PMID- 15466046
TI  - Effect of dimer dissociation on activity and thermostability of the alpha
      glucuronidase from Geobacillus stearothermophilus: dissecting the different
      oligomeric forms of family 67 glycoside hydrolases.
AB  - The oligomeric organization of enzymes plays an important role in many biological
      processes, such as allosteric regulation, conformational stability and thermal
      stability. alpha-Glucuronidases are family 67 glycosidases that cleave the alpha
      1,2-glycosidic bond between 4-O-methyl-D-glucuronic acid and xylose units as part
      of an array of hemicellulose-hydrolyzing enzymes. Currently, two crystal
      structures of alpha-glucuronidases are available, those from Geobacillus
      stearothermophilus (AguA) and from Cellvibrio japonicus (GlcA67A). Both enzymes
      are homodimeric, but surprisingly their dimeric organization is different,
      raising questions regarding the significance of dimerization for the enzymes'
      activity and stability. Structural comparison of the two enzymes suggests several
      elements that are responsible for the different dimerization organization.
      Phylogenetic analysis shows that the alpha-glucuronidases AguA and GlcA67A can be
      classified into two distinct subfamilies of bacterial alpha-glucuronidases, where
      the dimer-forming residues of each enzyme are conserved only within its own
      subfamily. It seems that the different dimeric forms of AguA and GlcA67A
      represent the two alternative dimeric organizations of these subfamilies. To
      study the biological significance of the dimerization in alpha-glucuronidases, we
      have constructed a monomeric form of AguA by mutating three of its interface
      residues (W328E, R329T, and R665N). The activity of the monomer was significantly
      lower than the activity of the wild-type dimeric AguA, and the optimal
      temperature for activity of the monomer was around 35 degrees C, compared to 65
      degrees C of the wild-type enzyme. Nevertheless, the melting temperature of the
      monomeric protein, 72.9 degrees C, was almost identical to that of the wild-type,
      73.4 degrees C. It appears that the dimerization of AguA is essential for
      efficient catalysis and that the dissociation into monomers results in subtle
      conformational changes in the structure which indirectly influence the active
      site region and reduce the activity. Structural and mechanistic explanations for
      these effects are discussed.

PMID- 15466047
TI  - Genomic studies with Escherichia coli MelR protein: applications of chromatin
      immunoprecipitation and microarrays.
AB  - Escherichia coli MelR protein is a transcription activator that is essential for
      melibiose-dependent expression of the melAB genes. We have used chromatin
      immunoprecipitation to study the binding of MelR and RNA polymerase to the melAB
      promoter in vivo. Our results show that MelR is associated with promoter DNA,
      both in the absence and presence of the inducer melibiose. In contrast, RNA
      polymerase is recruited to the melAB promoter only in the presence of inducer.
      The MelR DK261 positive control mutant binds to the melAB promoter but cannot
      recruit RNA polymerase. Further analysis of immunoprecipitated DNA, by using an
      Affymetrix GeneChip array, showed that the melAB promoter is the major, if not
      the sole, target in E. coli for MelR. This was confirmed by a transcriptomics
      experiment to analyze RNA in cells either with or without melR.

PMID- 15466048
TI  - Use of fluorescent-protein tagging to determine the subcellular localization of
      mycoplasma pneumoniae proteins encoded by the cytadherence regulatory locus.
AB  - Mycoplasma pneumoniae lacks a cell wall but has internal cytoskeleton-like
      structures that are assumed to support the attachment organelle and asymmetric
      cell shape of this bacterium. To explore the fine details of the attachment
      organelle and the cytoskeleton-like structures, a fluorescent-protein tagging
      technique was applied to visualize the protein components of these structures.
      The focus was on the four proteins--P65, HMW2, P41, and P24--that are encoded in
      the crl operon (for "cytadherence regulatory locus"), which is known to be
      essential for the adherence of M. pneumoniae to host cells. When the P65 and HMW2
      proteins were fused to enhanced yellow fluorescent protein (EYFP), a variant of
      green fluorescent protein, the fused proteins became localized at the attachment
      organelle, enabling visualization of the organelles of living cells by
      fluorescence microscopy. The leading end of gliding M. pneumoniae cells,
      expressing the EYFP-P65 fusion, was observed as a focus of fluorescence. On the
      other hand, when the P41 and P24 proteins were labeled with EYFP, the
      fluorescence signals of these proteins were observed at the proximal end of the
      attachment organelle. Coexpression of the P65 protein labeled with enhanced cyan
      fluorescent protein clearly showed that the sites of localization of P41 and P24
      did not overlap that of P65. The localization of P41 and P24 suggested that they
      are also cytoskeletal proteins that function in the formation of unknown
      structures at the proximal end of the attachment organelle. The fluorescent
      protein fusion technique may serve as a powerful tool for identifying components
      of cytoskeleton-like structures and the attachment organelle. It can also be used
      to analyze their assembly.

PMID- 15466050
TI  - lpt6, a gene required for addition of phosphoethanolamine to inner-core
      lipopolysaccharide of Neisseria meningitidis and Haemophilus influenzae.
AB  - We previously described a gene, lpt3, required for the addition of
      phosphoethanolamine (PEtn) at the 3 position on the beta-chain heptose (HepII) of
      the inner-core Neisseria meningitidis lipopolysaccharide (LPS), but it has long
      been recognized that the inner-core LPS of some strains possesses PEtn at the 6
      position (PEtn-6) on HepII. We have now identified a gene, lpt6 (NMA0408), that
      is required for the addition of PEtn-6 on HepII. The lpt6 gene is located in a
      region previously identified as Lgt-3 and is associated with other LPS
      biosynthetic genes. We screened 113 strains, representing all serogroups and
      including disease and carriage strains, for the lpt3 and lpt6 genes and showed
      that 36% contained both genes, while 50% possessed lpt3 only and 12% possessed
      lpt6 only. The translated amino acid sequence of lpt6 has a homologue (72.5%
      similarity) in a product of the Haemophilus influenzae Rd genome sequence.
      Previous structural studies have shown that all H. influenzae strains
      investigated have PEtn-6 on HepII. Consistent with this, we found that, among 70
      strains representing all capsular serotypes and nonencapsulated H. influenzae
      strains, the lpt6 homologue was invariably present. Structural analysis of LPS
      from H. influenzae and N. meningitidis strains where lpt6 had been insertionally
      inactivated revealed that PEtn-6 on HepII could not be detected. The translated
      amino acid sequences from the N. meningitidis and H. influenzae lpt6 genes have
      conserved residues across their lengths and are part of a family of proven or
      putative PEtn transferases present in a wide range of gram-negative bacteria.

PMID- 15466049
TI  - Complete genome sequence of the genetically tractable hydrogenotrophic methanogen
      Methanococcus maripaludis.
AB  - The genome sequence of the genetically tractable, mesophilic, hydrogenotrophic
      methanogen Methanococcus maripaludis contains 1,722 protein-coding genes in a
      single circular chromosome of 1,661,137 bp. Of the protein-coding genes (open
      reading frames [ORFs]), 44% were assigned a function, 48% were conserved but had
      unknown or uncertain functions, and 7.5% (129 ORFs) were unique to M.
      maripaludis. Of the unique ORFs, 27 were confirmed to encode proteins by the mass
      spectrometric identification of unique peptides. Genes for most known functions
      and pathways were identified. For example, a full complement of hydrogenases and
      methanogenesis enzymes was identified, including eight selenocysteine-containing
      proteins, with each being paralogous to a cysteine-containing counterpart. At
      least 59 proteins were predicted to contain iron-sulfur centers, including
      ferredoxins, polyferredoxins, and subunits of enzymes with various redox
      functions. Unusual features included the absence of a Cdc6 homolog, implying a
      variation in replication initiation, and the presence of a bacterial-like RNase
      HI as well as an RNase HII typical of the Archaea. The presence of alanine
      dehydrogenase and alanine racemase, which are uniquely present among the Archaea,
      explained the ability of the organism to use L- and D-alanine as nitrogen
      sources. Features that contrasted with the related organism Methanocaldococcus
      jannaschii included the absence of inteins, even though close homologs of most
      intein-containing proteins were encoded. Although two-thirds of the ORFs had
      their highest Blastp hits in Methanocaldococcus jannaschii, lateral gene transfer
      or gene loss has apparently resulted in genes, which are often clustered, with
      top Blastp hits in more distantly related groups.

PMID- 15466051
TI  - ParB of Pseudomonas aeruginosa: interactions with its partner ParA and its target
      parS and specific effects on bacterial growth.
AB  - The par genes of Pseudomonas aeruginosa have been studied to increase the
      understanding of their mechanism of action and role in the bacterial cell. Key
      properties of the ParB protein have been identified and are associated with
      different parts of the protein. The ParB- ParB interaction domain was mapped in
      vivo and in vitro to the C-terminal 56 amino acids (aa); 7 aa at the C terminus
      play an important role. The dimerization domain of P. aeruginosa ParB is
      interchangeable with the dimerization domain of KorB from plasmid RK2 (IncP1
      group). The C-terminal part of ParB is also involved in ParB-ParA interactions.
      Purified ParB binds specifically to DNA containing a putative parS sequence based
      on the consensus sequence found in the chromosomes of Bacillus subtilis,
      Pseudomonas putida, and Streptomyces coelicolor. The overproduction of ParB was
      shown to inhibit the function of genes placed near parS. This "silencing" was
      dependent on the parS sequence and its orientation. The overproduction of P.
      aeruginosa ParB or its N-terminal part also causes inhibition of the growth of P.
      aeruginosa and P. putida but not Escherichia coli cells. Since this inhibitory
      determinant is located well away from ParB segments required for dimerization or
      interaction with the ParA counterpart, this result may suggest a role for the N
      terminus of P. aeruginosa ParB in interactions with host cell components.

PMID- 15466052
TI  - Thirty-eight C-terminal amino acids of the coupling protein TraD of the F-like
      conjugative resistance plasmid R1 are required and sufficient to confer binding
      to the substrate selector protein TraM.
AB  - Coupling proteins (CPs) are present in type IV secretion systems of plant,
      animal, and human pathogens and are essential for DNA transfer in bacterial
      conjugation systems. CPs connect the DNA-processing machinery to the mating pair
      forming transfer apparatus. In this report we present in vitro and in vivo data
      that demonstrate specific binding of CP TraD of the IncFII R1 plasmid transfer
      system to relaxosomal protein TraM. With overlay assays and enzyme-linked
      immunosorbent assays we showed that a truncated version of TraD, termed TraD11
      (DeltaN155), interacted strongly with TraM. The apparent TraD11-TraM association
      constant was determined to be 2.6 x 10(7) liters/mol. Electrophoretic mobility
      shift assays showed that this variant of TraD also strongly bound to TraM when it
      was in complex with its target DNA. When 38 amino acids were additionally removed
      from the C terminus of TraD, no binding to TraM was observed. TraD15, comprising
      the 38 amino-acid-long C terminus of TraD, bound to TraM, indicating that the
      main TraM interaction domain resides in these 38 amino acids of TraD. TraD15
      exerted a dominant negative effect on DNA transfer but not on phage infection by
      pilus-specific phage R17, indicating that TraM-TraD interaction is important for
      conjugative DNA transfer but not for phage infection. We also observed that TraD
      encoded by the closely related F factor bound to TraM encoded by the R1 plasmid.
      Our results thus provide evidence that substrate selection within the IncF
      plasmid group is based on TraM's capability to select the correct DNA molecule
      for transport and not on substrate selection by the CP.

PMID- 15466053
TI  - Genome-wide transcriptional analysis of the cold shock response in wild-type and
      cold-sensitive, quadruple-csp-deletion strains of Escherichia coli.
AB  - A DNA microarray-based global transcript profiling of Escherichia coli in
      response to cold shock showed that in addition to the known cold shock-inducible
      genes, new genes such as the flagellar operon, those encoding proteins involved
      in sugar transport and metabolism, and remarkably, genes encoding certain heat
      shock proteins are induced by cold shock. In the light of strong reduction in
      metabolic activity of the cell after temperature downshift, the induction of
      sugar metabolism machinery is unexpected. The deletion of four csps (cspA, cspB,
      cspG, and cspE) affected cold shock induction of mostly those genes that are
      transiently induced in the acclimation phase, emphasizing that CspA homologues
      are essential in the acclimation phase. Relevance of these findings with respect
      to the known RNA chaperone function of CspA homologues is discussed.

PMID- 15466054
TI  - Evidence for polyadenylated mRNA in Pseudomonas aeruginosa.
AB  - In this paper, we report the synthesis of Pseudomonas aeruginosa cDNA in the
      presence of oligo(dT) primers. Hybridization of oligonucleotide DNA microarrays
      indicates that under the experimental conditions used, at least 43.7% of the
      expressed genes from P. aeruginosa PAO1, representing many different functional
      classes, can be detected by using oligo(dT)-primed cDNAs.

PMID- 15466055
TI  - Treponema pallidum fibronectin-binding proteins.
AB  - Putative adhesins were predicted by computer analysis of the Treponema pallidum
      genome. Two treponemal proteins, Tp0155 and Tp0483, demonstrated specific
      attachment to fibronectin, blocked bacterial adherence to fibronectin-coated
      slides, and supported attachment of fibronectin-producing mammalian cells. These
      results suggest Tp0155 and Tp0483 are fibronectin-binding proteins mediating T.
      pallidum-host interactions.

PMID- 15466056
TI  - Electronic curriculum implementation at North American dental schools.
AB  - Electronic curriculum, or E-curriculum, refers to computer-based learning
      including educational materials available on CD or DVD, online courses,
      electronic mechanisms to search the literature, email, and various applications
      of instructional technology including providing laptops to students, multimedia
      projection systems, and Internet-compatible classrooms. In spite of enthusiasm
      about the potential for E-curriculum to enhance dental education, there is
      minimal guidance in the literature to assist schools with implementation. The
      study objectives were: 1) identify U.S. and Canadian dental schools that have
      initiated mandatory laptop programs and assess cost, faculty development issues,
      extent of curricular use, problems, and qualitative perceptions; 2) determine the
      extent to which twenty-two other E-curriculum resources were available and used
      at North American dental schools; and 3) identify factors that influenced E
      curriculum implementation. A twenty-six item questionnaire, known as the
      Electronic Curriculum Implementation Survey (ECIS), was mailed to all sixty-six
      North American dental schools (ten Canadian and fifty-six U.S. schools) during
      2002-03 with a response rate of 100 percent. Twenty-five of the twenty-six ECIS
      questions employed a menu-driven, forced choice format, but respondents could
      provide amplifying comments. Fifty-three questionnaires were completed by
      associate deans for academic affairs, three by deans, and ten by instructional
      technology (IT) managers, IT committee chairs, or directors of dental informatics
      departments. The survey found that E-curriculum implementation among North
      American dental schools is following the classic innovation pattern in which a
      few early adopting institutions proceed rapidly while the majority of potential
      adopters make modifications slowly. Fourteen U.S. dental schools have established
      mandatory laptop programs for students. Ten of these laptop programs were created
      in the past two years; respondents reported numerous growing pains but were
      generally pleased with their progress. Other E-curriculum capabilities were
      incorporated into courses more frequently at laptop schools than the fifty-two
      non-laptop schools including websites, online course evaluations, and instructor
      use of email to communicate with students. Few dental schools use online courses,
      and at most schools, few faculty have received training in online instructional
      techniques. Virtually all North American dental schools have provided substantial
      instructional technology resources to their faculty, but use of twenty-two
      components and capabilities of E-curriculum was limited, especially at schools
      without laptop programs. Various faculty-related issues were reported as
      implementation barriers including lack of time, skill, and incentive to develop
      educational software. We conclude that many North American dental schools,
      especially those with laptop programs, are functioning at the "learn by doing"
      phase of initial implementation in a four-stage innovation adoption model. E
      curriculum planners should pay close attention to implementation problems that
      occur at this stage where many innovation efforts break down.

PMID- 15466057
TI  - Relationship between small group problem-solving activity and lectures in health
      science curricula.
AB  - Components of problem-based education, such as small group teaching, are being
      implemented in diverse health curricula. Implementation, however, is often
      motivated by the intuitive appeal of many problem-based learning components, when
      what is needed is the detailed examination of how these components support
      students' integration of knowledge as well as continuity of their learning
      experiences. This study presents an investigation of the relationship between
      lecture and small group teaching (SGT) in a medical curriculum. Four problem
      oriented SGT sessions representing diverse topics in the first-year curriculum
      and their corresponding lectures were videotaped and analyzed using techniques of
      concept mapping, where the broad concepts from the lectures were identified and
      matched to the case-specific concepts in the small group sessions. The results
      show that lectures function as an anchor for the students' discussion of issues
      relevant to clinical problem-solving and interventions in small group sessions.
      These discussions extended to contextual aspects of clinical practice that were
      not dealt with in the lectures, such as ethical/cultural issues around the
      treatment of patients. Furthermore, small group environments were found to
      promote discussions that allowed the integration of information from different
      sources and encompassed concepts across a number of disciplines. These results
      suggest that carefully designed small group sessions serve the purposes of 1)
      illustrating broader concepts in lectures to case-specific, clinically relevant
      problem-solving and 2) promoting knowledge integration from diverse sources of
      information. The implications of these results for learning and reasoning in
      health science curricula are discussed.

PMID- 15466058
TI  - Factors influencing use of dental services in rural and urban communities:
      considerations for practitioners in underserved areas.
AB  - Individuals' utilization of dental services depends upon an array of factors,
      including access to care, financial restrictions, attitudes toward dental care,
      and dental fear. These factors, in turn, may vary across geographic locations and
      demographic groups. The goals of this study were to assess the use of dental
      services in both rural and urban areas of Kentucky and to examine challenges
      facing practitioners in rural areas. Individuals sampled from a rural population
      and patients in rural and urban dental clinics completed questionnaires about use
      of dental services, self-rated dental health, and dental fear. While these
      variables were strongly interrelated, differences emerged across locations.
      Patients in the urban area reported having more dental insurance but not better
      dental health. Patients in more rural areas reported seeking more emergency
      dental treatment but not more dental fear. While these factors are important
      considerations across locations, dental practitioners in rural areas in
      particular should be aware of barriers to dental care facing individuals in these
      areas. They have unique opportunities to provide education to their patients
      regarding the importance of dental care and the role of oral health in overall
      physical health.

PMID- 15466059
TI  - Early clinical experience for first-year dental students.
AB  - Over the past three years we have exposed our first-year dental students at Case
      Western Reserve University School of Dental Medicine to an early clinical
      experience. Following a seventy-two-hour didactic and laboratory course, first
      year students spend over 100 hours treating school children in twenty-eight
      elementary and middle schools in the Cleveland Municipal School District. Not
      only do dental students learn a clinical procedure, but more importantly they
      experience the need for health care, in particular, dental care among those less
      fortunate than themselves. The experience strengthens their desire to help the
      under-served, their understanding of the problems many face in obtaining oral
      health care, and their commitment to addressing these issues. Themes from student
      reflection papers are summarized.

PMID- 15466060
TI  - Restorative treatment strategies reported by French university teachers.
AB  - Disparities among dental schools concerning the teaching and practice of
      cariology and operative dentistry can lead to variations in students' treatment
      modalities that can have health and economic consequences for patients and third
      party providers. The purpose of this study was to assess caries management
      strategies taught in French dental schools employing a questionnaire used in a
      previous study involving private dentists. The study population consisted of 180
      teachers of operative dentistry. Each teacher received a questionnaire and a
      reply-paid envelope. The questionnaire assessed their treatment strategies,
      knowledge and beliefs about selected aspects of diagnosis, and treatment of
      dental caries. After one reminder, the response rate was 49.1 percent. The
      results illustrate a wide disparity among French teachers concerning restorative
      treatment thresholds for approximal surfaces, opinions about the rate of caries
      progression, and the need to monitor lesions near the DEJ. The teachers'
      attitudes differed from those of private practitioners: they tended to intervene
      surgically at a later stage, but they would intervene earlier in the treatment of
      the carious process than would Scandinavian dentists. This study may help in
      encouraging dental faculties to develop a consensus on issues related to
      diagnosis and management of dental caries.

PMID- 15466061
TI  - Strategies for training standardized patient instructors for a competency exam.
AB  - The Common Achievement Test (CAT) in Japan, which will be implemented in 2005,
      involves a medical interview that is the core task to be completed by students
      during an Objective Structured Clinical Examination (OSCE).
      Standardized/Simulated Patient instructors (SPs), posing as patients in medical
      interviews, are trained in standard fashion in terms of expression of symptoms as
      well as the emotional affect of actual patients. Institution of appropriate
      training programs for SP instructors in the CAT is also necessary. We trained
      seven individuals to function as standardized patients (in-school SPs) during a
      three-day SP training program described in this article. Following completion of
      the OSCE, we conducted a comparison study among evaluations completed by the
      evaluators and two types of SP instructors. We observed high correlation,
      according to Spearman significance testing, between scores of evaluators and
      those of both newly trained in-school SPs and veteran SPs who had more than five
      years of experience. Correlation coefficients between the veteran SPs (r=0.77)
      and the in-school SPs (r=0.73) were nearly identical. These results suggest that
      our training program for SP instructors is an effective protocol, particularly
      with respect to reliability and efficiency.

PMID- 15466062
TI  - Underrepresented minority dental school enrollment: continued vigilance required.

PMID- 15466063
TI  - Effects of a primary care-based intervention on violent behavior and injury in
      children.
AB  - OBJECTIVE: Although many major health care organizations have made
      recommendations regarding physicians' roles in preventing youth violence, the
      efficacy of violence prevention strategies in primary care settings remains to be
      empirically tested. METHODS: We conducted a randomized, controlled trial to
      evaluate the effects of an office-based intervention on children's violent
      behaviors and violence-related injuries. Children 7 to 15 years of age who
      presented at 8 pediatric practices and scored positive on a brief psychosocial
      screening test (n = 224) were randomly assigned to an intervention group
      (clinicians saw the screening test results during the visit and a telephone-based
      parenting education program was made available to clinicians as a referral
      resource for parents) or a control group (clinicians did not see the screening
      test results). RESULTS: Compared with control subjects, at 9 months after study
      enrollment, children in the intervention group exhibited decreases in aggressive
      behavior (adjusted mean difference: -1.71; 95% confidence interval [CI]: -2.89 to
      -0.53), delinquent behavior (adjusted mean difference: -0.71; 95% CI: -1.28 to 
      0.13), and attention problems (adjusted mean difference: -1.02; 95% CI, -1.77 to 
      0.26) on the Child Behavior Checklist. Children in the intervention group had
      lower rates of parent-reported bullying (adjusted odds ratio: 4.43; 95% CI: 1.87
      10.52), physical fighting (adjusted odds ratio: 1.79; 95% CI: 1.11-2.87), and
      fight-related injuries requiring medical care (adjusted odds ratio: 4.70; 95% CI:
      1.33-16.59) and of child-reported victimization by bullying (adjusted odds ratio:
      3.23; 95% CI: 1.96-5.31). CONCLUSIONS: A primary care-based intervention that
      includes psychosocial screening and the availability of a parenting education
      resource can decrease violent behavior and injury among youths.

PMID- 15466065
TI  - Conditions leading to pediatric cardiology consultation in a tertiary academic
      hospital.
AB  - OBJECTIVE: To determine the basis for cardiac consultations for pediatric
      patients in an academic hospital setting. METHODS: The activities of the
      cardiology consultation service were tabulated for 12 months, from July 2001 to
      June 2002. Patients were identified from 4 sources, ie, a monthly log of patient
      encounters maintained by the consultation service, encounter forms submitted to
      the billing office, consultation notes maintained in a central file, and a
      departmental list of echocardiography studies. Patients who required clearance
      for noncardiac surgical procedures were generally evaluated in the cardiology
      clinic and not by the consultation service. Patient data were obtained from
      consultation and echocardiography reports and from hospital computer-based
      records for discharge summaries for inpatient admissions, emergency department
      encounter summaries, and laboratory reports. For each patient, consultations were
      tabulated as separate encounters if they occurred on different days in the
      emergency department, during separate admissions, or for different clinical
      concerns during a single admission. RESULTS: A total of 2071 consultations were
      performed for 1724 patients. The age at the time of consultation was 6.6 +/- 9.3
      years (median: 1.2 years; range: 1 day to 60.6 years). A total of 1507 patients
      (87.4%) had a single consultation; 217 patients (12.6%) had multiple encounters,
      ranging from 2 to 9, accounting for 564 consultations (27.2%). Clinical concerns
      included murmurs (18.5%), cardiac function (12.7%), arrhythmias (12.7%),
      intercurrent illnesses among cardiac patients (11.3%), cyanosis (6.3%), syndromes
      (5.7%), chest pain (5.2%), syncope/dizziness (4.5%), subacute endocarditis
      (4.4%), follow-up evaluations of fetal diagnoses (4.3%), Kawasaki disease (3.4%),
      cor pulmonale (3%), recent cardiac surgery or catheterization (1.6%),
      cerebrovascular accidents (1.2%), and miscellaneous conditions. Four diagnoses
      accounted for 91% of murmur evaluations, ie, patent ductus arteriosus,
      ventricular septal defects, innocent murmurs, and pulmonary branch murmur of
      infancy. The most common murmur diagnosis in the neonatal intensive care unit was
      patent ductus arteriosus (68%), in the well-child nursery was ventricular septal
      defect (64%), and on the medical ward was innocent murmur (62%). The most common
      basis for evaluation of function was oncologic disease. Among patients evaluated
      for function, there were 3 new diagnoses of structural congenital heart disease,
      all involving neonates with aortic arch obstruction. Approximately two-thirds of
      arrhythmias were supraventricular in origin. The most common arrhythmias
      requiring treatment were supraventricular tachycardia and atrial
      flutter/fibrillation, the latter occurring mainly among older patients with
      structural heart disease. Diagnoses made with fetal echocardiography accounted
      for 14.3% of newborn consultations and included 83% of patients with cyanotic
      cardiac disease. Three syndromes accounted for 57% of consultations for this
      indication, ie, VACTERL association (vertebral anomalies, anal atresia,
      congenital heart disease, tracheoesophageal fistula, renal abnormality, and limb
      anomalies), trisomy 21, and infant of diabetic mother. Chest pain and
      syncope/dizziness were frequently evaluated in the emergency department and, in
      this setting, accounted for 13 and 10% of all evaluations and 19 and 25% of
      evaluations for new patients, respectively. For patients evaluated for chest
      pain, the most common basis was musculoskeletal/costochondritic (42%) or
      idiopathic (22%). There was a cardiac or pericardial basis in 11% of cases; these
      patients either had known heart disease associated with this complication or
      systemic symptoms, abnormal cardiac auscultatory findings, and
      electrocardiographic features of pericarditis. Syncope/dizziness most commonly
      had a vasovagal (50.5%) or orthostatic (24.7%) basis. There was a cardiac basis
      in 5.4% of cases; these patients were more likely to have symptoms associated
      with exercise. Although endocarditis was a frequent clinical concern (91
      patients), only 3 cases were identified, involving 2 patients with structural
      heart disease and 1 neonate with an indwelling intracardiac catheter. Two other
      patients had central venous lines, intravascular thrombus, and fungemia. Kawasaki
      disease was the most common acquired condition leading to consultation. Cor
      pulmonale was most commonly screened among patients with congenital diaphragmatic
      hernia, chronic lung disease of prematurity, pneumonitis, reactive airway
      disease, or cystic fibrosis. Patients with recent cardiac surgery or cardiac
      catheterization typically had postpericardiotomy syndrome or complications
      associated with vascular access. Approximately 20% of cases of cerebrovascular
      accidents had a cardiac basis. CONCLUSIONS: Although a variety of conditions were
      assessed, some were encountered more frequently. Future educational curricula
      developed for cardiac training of pediatric residents should appropriately
      emphasize conditions necessitating consultation.

PMID- 15466064
TI  - Equivalent lengths of stay of pediatric patients hospitalized in rural and
      nonrural hospitals.
AB  - BACKGROUND: Many children receive their care at local hospitals outside of a
      large urban area. There may be differences in the length of stay (LOS) between
      children hospitalized in rural versus urban hospitals. This study compared the
      differences in LOS, conditional LOS (CLOS), odds of prolonged stay, and 21-day
      readmission rates for children with 19 medical conditions and 9 surgical
      procedures admitted to rural, community, and large urban hospitals. METHODS:
      Discharge records for the hospitalizations of children 1 to 17 years of age were
      obtained from the New York Department of Public Health Statewide Planning and
      Research Cooperative System and the Pennsylvania Health Care Cost Containment
      Council for April 1996 to July 1998. The 19 medical and 9 surgical conditions
      were identified with the principal condition and procedure codes. Hospitals were
      classified into 1 of 5 geographic categories on the basis of United States rural
      urban continuum codes, ie, large urban, suburban, moderate urban, small urban, or
      rural. LOS was defined as the period of time between hospital admission and
      discharge. Readmission rates were calculated for 21 days after discharge from the
      hospital. A prolonged stay for each condition was defined as any admission
      lasting beyond the prolongation point, or the day at which the rate of discharge
      began to decline, as determined with the Hollander-Proschan statistic. This
      aspect of LOS describes the ability of providers to treat uncomplicated cases of
      that specific principle diagnosis. CLOS, as a marker for the management of
      complicated cases, was defined as the LOS beyond the prolongation point. Cox and
      logistic regression models were developed to describe the geographic effects on
      the 4 outcome variables, after severity adjustment with 32 demographic and 11
      comorbidity variables and adjustment for hospital clustering. RESULTS: Medical (N
      = 114,787) and surgical (N = 29,156) admissions to rural hospitals (N = 12,367)
      had similar outcomes, compared with all geographic categories except the large
      urban category. Medical patients admitted to rural hospitals had a shorter LOS
      (12% increase in discharge rate), a shorter CLOS (12% increase in discharge
      rate), and lower odds of prolonged stay (odds ratio: 0.80), compared with those
      in large urban hospitals. Surgical patients admitted to rural hospitals had a
      shorter LOS (12% increase in discharge rate) and lower odds of prolonged stay
      (odds ratio: 0.81), compared with those in large urban hospitals. For individual
      conditions, rural hospitals in general had similar or improved LOS, compared with
      all other hospitals in the 2 states. The addition of hospital-level variables
      failed to change the results of the primary models. CONCLUSIONS: In their
      treatment of pediatric hospitalized patients, rural hospitals were not
      significantly different from hospitals in all geographic regions other than large
      urban areas. Rural hospitals appear to deliver similar care, compared with
      nonrural hospitals, for many of the common pediatric conditions included in this
      study. Additional research is needed to apply these results to other regions or
      states with different geographic distributions of hospitals and children, in
      order to determine the overall impact on the regionalization of pediatric care.

PMID- 15466066
TI  - Early preventive dental visits: effects on subsequent utilization and costs.
AB  - OBJECTIVE: To determine the effects of early preventive dental visits on
      subsequent utilization and costs of dental services among preschool-aged
      children. DESIGN: This investigation studied North Carolina children who were
      enrolled continuously in Medicaid from birth for a 5-year period. Our research
      design was a longitudinal cohort study that relied on 4 large administrative
      datasets, including North Carolina composite birth records from 1992, Medicaid
      enrollment and claims files from 1992 to 1997, and the Area Resource File. Our
      outcome measures included type of use and dentally related costs. RESULTS: Of the
      53591 Medicaid-enrolled children born in 1992, 9204 were continuously enrolled
      for 5 years and met our inclusion criteria. Twenty-three children had their first
      preventive dental visit before 1 year of age, 249 between 1 and 2 years, 465
      between 2 and 3 years, 915 between 3 and 4 years, and 823 between 4 and 5 years.
      Children who had their first preventive dental visit by age 1 were more likely to
      have subsequent preventive visits but were not more likely to have subsequent
      restorative or emergency visits. Those who had their first preventive visit at
      age 2 or 3 were more likely to have subsequent preventive, restorative, and
      emergency visits. The age at the first preventive dental visit had a significant
      positive effect on dentally related expenditures, with the average dentally
      related costs being less for children who received earlier preventive care. The
      average dentally related costs per child according to age at the first preventive
      visit were as follows: before age 1, 262 dollars; age 1 to 2, 339 dollars; age 2
      to 3, 449 dollars; age 3 to 4, 492 dollars; age 4 to 5, 546 dollars. CONCLUSIONS:
      Our results should be interpreted cautiously, because of the potential for
      selection bias; however, we concluded that preschool-aged, Medicaid-enrolled
      children who had an early preventive dental visit were more likely to use
      subsequent preventive services and experience lower dentally related costs. In
      addition, children from racial minority groups had significantly more difficulty
      in finding access to dental care, as did those in counties with fewer dentists
      per population.

PMID- 15466067
TI  - The mortality index for neonatal transportation score: a new mortality prediction
      model for retrieved neonates.
AB  - OBJECTIVE: To develop a mortality prediction score for retrieved neonates based
      on the information given at the first telephone contact with a retrieval service.
      METHODS: Data from the New South Wales Newborn and Pediatric Emergency Transport
      Service database were examined. Analysis was performed with the results for 2504
      infants (median gestational age: 36 weeks; range: 24-43 weeks) who were <72 hours
      of age at the time of referral and whose outcome (neonatal death or survival) was
      known. The study population was divided randomly into 2 halves, the derivation
      and validation cohorts. Univariate analysis was performed to identify variables
      in the derivation cohort related to neonatal death. The variables were entered
      into a multivariate logistic regression analysis with neonatal death as the
      outcome. Receiver operator characteristic (ROC) curves were constructed with the
      regression model and data from the derivation cohort and then the validation
      cohort. The results were used to generate an integer-based score, the Mortality
      Index for Neonatal Transportation (MINT) score. ROC curves were constructed to
      assess the ability of the MINT score to predict perinatal and neonatal death.
      RESULTS: A 7-variable (Apgar score at 1 minute, birth weight, presence of a
      congenital anomaly, and infant's age, pH, arterial partial pressure of oxygen,
      and heart rate at the time of the call) model was constructed that generated
      areas under ROC curves of 0.82 and 0.83 for the derivation and validation
      cohorts, respectively. The 7 variables were then used to generate the MINT score,
      which gave areas under ROC curves of 0.80 for both neonatal and perinatal death.
      CONCLUSION: Data collected at the first telephone contact by the referring
      hospital with a regionalized transport service can identify neonates at the
      greatest risk of dying.

PMID- 15466068
TI  - Parental feeding attitudes and styles and child body mass index: prospective
      analysis of a gene-environment interaction.
AB  - BACKGROUND: Parental feeding styles were linked to child weight in cross
      sectional studies, which were unable to test the direction of effect. Prospective
      studies can best establish causal relationships among such variables. OBJECTIVE:
      We tested the 2-year stability of parental feeding attitudes and styles and
      investigated whether these variables predict child body mass index (BMI) z scores
      2 years later. We evaluated whether these associations were dependent on
      children's predisposition to obesity. METHODS: Participants were 57 families
      enrolled in an Infant Growth Study of children born at high risk or low risk for
      obesity, on the basis of maternal prepregnancy overweight or leanness. Children
      were evaluated for weight and height at 3, 5, and 7 years of age. Measures of
      parental feeding attitudes and styles were ascertained with the Child Feeding
      Questionnaire at 5 and 7 years of age. Correlation and multiple regression
      analyses tested whether parental feeding styles at age 5 predicted increased
      child BMI z scores 2 years later. RESULTS: Parental feeding attitudes and styles
      were stable for child ages of 5 to 7 years. With respect to feeding attitudes,
      perceived responsibility at age 5 predicted reduced child BMI z scores at age 7
      among low-risk families, whereas child weight concern and perceived child weight
      predicted increased child BMI z scores among high-risk families. With respect to
      feeding styles, monitoring predicted reduced child BMI z scores at age 7 among
      low-risk children. In contrast, restriction predicted higher BMI z scores and
      pressure to eat predicted reduced BMI z scores among high-risk children. These
      associations remained significant after controlling for child weight status at
      age 3. CONCLUSIONS: The relationship between parental feeding styles and child
      BMI z scores depends on child obesity predisposition, suggesting a gene
      environment interaction. Among children predisposed to obesity, elevated child
      weight appears to elicit restrictive feeding practices, which in turn may produce
      additional weight gain. Parenting guidelines for overweight prevention may
      benefit from consideration of child characteristics such as vulnerability to
      obesity and current weight status.

PMID- 15466069
TI  - Respiratory syncytial virus hospitalizations among American Indian and Alaska
      Native infants and the general United States infant population.
AB  - OBJECTIVE: To determine the burden of respiratory syncytial virus (RSV) disease
      among American Indian (AI) and Alaska Native (AN) infants, by examining RSV
      associated hospitalizations. METHODS: Infant hospitalizations from 1997 through
      2001 with RSV listed as a diagnosis were selected by using Indian Health
      Service/tribal hospital discharge data for AIs/ANs and National Hospital
      Discharge Survey data for the general US population. RESULTS: In 2000-2001, RSV
      disease was listed as a diagnosis for 14.4% of all AI/AN infant hospitalizations,
      with bronchiolitis attributable to RSV infection (12.2%) being among the top 5
      listed diagnoses. The rate of RSV-specific hospitalizations was 34.4
      hospitalizations per 1000 infants for AI/AN infants and 27.4 hospitalizations per
      1000 births for the general US infant population. The hospitalization rates for
      AI/AN infants living in the Alaska and Southwest regions (70.9 and 48.2
      hospitalizations per 1000 infants, respectively) were much higher than the
      overall rate for US infants. CONCLUSIONS: RSV infection is one of the leading
      causes of hospitalization among all infants in the United States, and AI/AN
      infants living in the Southwest and Alaska regions are at especially high risk
      for hospitalizations associated with RSV infection. Development of vaccines,
      antiviral agents, and other strategies to prevent RSV disease could yield
      substantial public health benefits.

PMID- 15466070
TI  - Adolescents' beliefs about the risks involved in smoking "light" cigarettes.
AB  - BACKGROUND: Light cigarettes have been marketed by the tobacco industry as being
      a healthier smoking choice, a safe alternative to cessation, and a first step
      toward quitting smoking altogether. Research, however, has failed to show a
      reduction in smoking-related health risks, an increase in rates of smoking
      cessation, a decrease in the amount of carbon monoxide or tar released, or a
      reduction in the rates of cardiovascular disease or lung cancer associated with
      light cigarette use, compared with regular cigarette use. Nevertheless, more than
      one-half of adolescent smokers in the United States smoke light cigarettes. This
      study is the first to investigate adolescents' perception of the risks associated
      with smoking light cigarettes, as well as adolescents' attitudes and knowledge
      about the delivery of tar and nicotine, health risks, social effects, addiction
      potential, and ease of cessation with light cigarettes, compared with regular
      cigarettes. DESIGN: Participants were 267 adolescents (mean age: 14.0 years) who
      completed a self-administered questionnaire during class time. After reading
      scenarios in which they imagined that they smoked regular or light cigarettes,
      participants estimated the chances that they would personally experience 7
      smoking-related health risks and 3 addiction risks. Participants also responded
      to 14 items concerning their attitudes and knowledge about light cigarettes
      versus regular cigarettes. RESULTS: Participants thought that they would be
      significantly less likely to get lung cancer, have a heart attack, die from a
      smoking-related disease, get a bad cough, have trouble breathing, and get
      wrinkles when smoking light cigarettes, compared with regular cigarettes, for the
      rest of their lives. Furthermore, when participants were asked how long it would
      take to become addicted to the 2 cigarette types, they thought it would take
      significantly longer to become addicted to light versus regular cigarettes.
      Adolescents also thought that their chances of being able to quit smoking were
      higher with light versus regular cigarettes. Similarly, when participants were
      asked how easy it would be to quit smoking the 2 cigarette types, they thought it
      would be significantly easier for them to quit smoking light cigarettes than
      regular cigarettes. Adolescents agreed or strongly agreed that regular cigarettes
      deliver more tar than light cigarettes and that light cigarettes deliver less
      nicotine than regular cigarettes. CONCLUSIONS: Overall, the results of this study
      show that adolescents hold misperceptions in both their personal risk estimates
      and their general attitudes about the health risks, addictive properties, and
      ease of cessation associated with light cigarettes. With a variety of light and
      ultralight cigarettes on the market, adolescents are led to think that there is a
      progression of safety levels to choose from when deciding which cigarettes to
      smoke. This illusion of control over health outcomes contributes to an
      underestimation of risks associated with smoking light cigarettes and supports
      these misperceptions. These results are of concern, given evidence suggesting
      that, if adolescents think they are less vulnerable to smoking-related health
      risks (ie, lung cancer), then they are more likely to initiate smoking.
      Furthermore, there is evidence that adolescents are not fully aware of the
      addictive nature of cigarettes and therefore think that they can experiment with
      smoking during adolescence without becoming addicted or experiencing any health
      consequences. The data presented here support concerns regarding smoking
      addiction; adolescents might be even more inclined to smoke light cigarettes to
      delay addiction. Without correct information about light cigarettes, adolescents
      are unable to make informed decisions about their smoking behaviors. The findings
      presented here strongly suggest that health care practitioners need to talk to
      their adolescent clients not only about the overall risks of smoking but also
      about the specific risks associated with smoking light cigarettes and other
      tobacco varieties, including the potential for addiction and long-term health
      consequences. Information shared with adolescents about light cigarettes, both
      individually by health care practitioners and at the population level via counter
      advertising campaigns, may be successful in changing current misperceptions, and
      ultimately light cigarette smoking patterns, among youth.

PMID- 15466071
TI  - Recombinant human growth hormone treatment for dilated cardiomyopathy in
      children.
AB  - OBJECTIVE: Dilated cardiomyopathy (DCM) is one of the most common causes of heart
      failure among children and is often progressive despite maximal medical therapy.
      Heart failure is characterized by a number of neurohormonal abnormalities,
      including derangements in the growth hormone (GH)/insulin-like growth factor-1
      (IGF-1) signaling axis. Decreased serum levels of GH, which acts on cardiac
      myocytes primarily through IGF-1, are associated with impaired myocardial growth
      and function, which can be improved with restoration of GH/IGF-1 homeostasis. In
      animal models and among human adults with heart failure attributable to DCM,
      treatment with GH results in acquisition of left ventricular (LV) mass and
      improved LV function, through a combination of mechanisms. We undertook this
      study to determine the effects of recombinant human GH on LV function and mass
      among children with stable LV dysfunction attributable to DCM. METHODS: We
      performed a prospective, single-center, randomized, partially blinded, crossover
      trial among children 1 to 19 years of age with DCM and cardiac dysfunction of >
      or =6-month duration. After enrollment, patients were randomly assigned to
      receive treatment for 6 months with either conventional therapy (determined by
      the patient's primary cardiologist) plus recombinant human GH (0.025-0.04 mg/kg
      per day), administered as daily subcutaneous injections, or conventional therapy
      alone. Patients were then crossed over to the other treatment strategy for 6
      months. The primary outcome measure was change in LV shortening fraction (SF).
      Other echocardiographic indices of LV function, somatic growth, and
      somatotropic/thyroid hormone levels were also monitored. RESULTS: Only 8 of an
      intended 15 patients were enrolled, because of a combination of factors. Two
      patients withdrew during the study as a result of declining LV function requiring
      transplantation. LV SF did not change significantly during GH treatment, although
      both LV SF and LV SF z score were higher 6 months after cessation of GH treatment
      than at baseline. LV ejection fraction increased during GH therapy to a degree
      that approached significance. Height and weight percentiles for age increased
      significantly during GH therapy and remained higher 6 months after treatment.
      Annualized height velocity during GH treatment (13.7 +/- 3.3 cm/year, >97th
      percentile for all patients) was significantly higher than that after GH
      discontinuation (3.2 +/- 3.5 cm/year). Serum levels of IGF-1 and IGF-binding
      protein-3 were significantly higher after 6 months of GH treatment and 6 months
      after discontinuation of GH treatment than at baseline. There were no adverse
      events related to GH treatment. DISCUSSION: In this prospective, single-center,
      randomized, partially blinded, crossover trial, recombinant human GH was
      administered to 8 pediatric patients with stable chronic heart failure secondary
      to DCM. Because of unanticipated difficulty enrolling eligible patients, the
      study was underpowered to detect changes in our primary outcome measure of the
      magnitude we projected. Nevertheless, we did observe several notable
      cardiovascular effects of GH treatment, including a trend toward improved LV
      ejection fraction during the course of GH treatment and significantly improved LV
      SF, SF z score, and LV end systolic stress z score 6 months after discontinuation
      of GH treatment (relative to baseline values). Given the fact that levels of IGF
      1, the primary myocardial effector of GH signaling, remained significantly higher
      6 months after GH treatment than at baseline, the improvement in LV functional
      indices 6 months after discontinuation of therapy may represent progression or
      perpetuation of a GH treatment effect. In addition to its cardiovascular effects,
      GH therapy was associated with significant acceleration of somatic growth. The
      benefits of GH were not associated with significant attributable side effects,
      although 2 patients developed progressive LV dysfunction during the study and
      underwent cardiac transplantation.

PMID- 15466072
TI  - Validation of a multistage asthma case-detection procedure for elementary school
      children.
AB  - OBJECTIVE: The purpose of this study was to validate a 3-stage asthma case
      detection procedure for elementary school-aged children. METHODS: The study was
      performed in 10 elementary schools in 4 inner-city school systems, with a total
      enrollment of 3539 children. Results of the case-detection procedure were
      compared with the diagnosis of an asthma specialist study physician, to determine
      the sensitivity and specificity of the case-detection procedure. RESULTS: Ninety
      eight percent of children returned the asthma symptoms questionnaires, and 79% of
      those children consented to additional testing. Results indicated that the 3
      stage procedure had good validity, with sensitivity, specificity, and predictive
      value of 82%, 93%, and 93%, respectively. A 2-stage procedure using
      questionnaires and spirometry had similar validity, with sensitivity,
      specificity, and predictive value of 78%, 93%, and 93%, respectively. However,
      given the time and expense associated with the 2- or 3-stage procedure and the
      difficulty of obtaining physician follow-up evaluation of the case-detection
      diagnosis, schools may prefer to use a 2-item questionnaire that has a lower
      sensitivity (66%) but higher specificity (96%) and predictive value (95%).
      CONCLUSIONS: Case-detection programs are generally well received by school
      personnel and can identify children with unrecognized or undiagnosed disease, as
      well as those with a current diagnosis but poorly controlled disease. This study
      yields substantial information regarding the validity, yield, and specific types
      of children who might be identified with the use of such procedures. For the
      choice of the method of case detection used in a school, the strengths and
      weaknesses of each procedure, as well as the resources available for case
      detection, physician referral, and follow-up procedures, must be considered.

PMID- 15466073
TI  - Treatment of urinary tract infections among febrile young children with daily
      intravenous antibiotic therapy at a day treatment center.
AB  - OBJECTIVE: Urinary tract infections (UTIs) are common among infants and toddlers.
      Children can be treated effectively with short courses (2-4 days) of intravenous
      (IV) therapy followed by oral therapy. If IV therapy is chosen, use of once-daily
      dosing may allow outpatient management instead of hospital admission. However, no
      description of ambulatory treatment with IV antibiotics of UTI among febrile
      children has been reported to date. We aimed to describe the feasibility and
      complications of outpatient management with IV antibiotics of UTI among febrile
      children, at the day treatment center (DTC) of a tertiary-care pediatric
      hospital. METHODS: Between April 1, 2002, and March 31, 2003, a prospective
      cohort of patients 3 months to 5 years of age who were examined in the emergency
      department (ED) and diagnosed as having presumed febrile UTI were treated
      according to a clinical protocol. Patients were treated at the DTC unless they
      met exclusion criteria, in which case they were hospitalized. The DTC was open 7
      days per week, including holidays, from 8:30 am to 4:30 pm. At the DTC, patients
      were initially treated with a daily dose of IV gentamicin, until the child had
      been afebrile for at least 24 hours, and with oral amoxicillin, until preliminary
      urine culture results were available. Children allergic to penicillin received
      gentamicin only. IV antibiotics were administered through peripheral IV access;
      the IV catheter's patency was maintained with injection of 50 U of heparin once
      daily throughout the treatment period. Parental satisfaction with the DTC
      experience was assessed with an anonymous, self-administered questionnaire.
      RESULTS: Two hundred ninety-one episodes of presumed febrile UTI were diagnosed
      in the ED, of which 212 (72.9%) were sent to the DTC. There were 71 hospital
      admissions (24.4%); in 9 of these instances, the child was admitted because
      parents refused or were unable to comply with DTC treatment. Adherence to the
      treatment protocol in the ED was excellent; in 92.1% of presumed febrile UTI
      episodes (268 of 291 episodes), the patient was referred to the appropriate
      setting for treatment. In 8 instances, patients who met an exclusion criterion
      were sent to the DTC. They should have been hospitalized, according to the
      protocol. At the DTC, a final diagnosis of UTI was made in 178 of the 212
      episodes (84%). Patients treated at the DTC, with a final diagnosis of UTI, had a
      median age of 12.0 months (range: 3-68 months), and their mean initial
      temperature was 39.2 degrees C (SD: 1.1 degrees C). Patients were afebrile by 24
      hours in 52% of UTI episodes and by 48 hours in 82%. Minor problems with IV
      access occurred in 9.0% of cases. The duration of IV antibiotic therapy at the
      DTC was 1.9 days (SD: 0.9 day). The mean number of visits to the DTC, including
      appointments for renal ultrasound and voiding cystourethrography evaluations, was
      3.5 (SD: 0.9). Parents were present at all scheduled visits in 98.9% of cases.
      Four patients needed to be hospitalized from the DTC, but in only 1 case was
      hospital admission related to UTI treatment. Four patients with UTI treated in
      the DTC had positive blood cultures, 2 with Escherichia coli (both successfully
      treated at the DTC) and 2 with contaminants. For 4 children treated at the DTC,
      UTI was caused by gentamicin-resistant E coli. One patient became afebrile within
      24 hours after treatment initiation with IV gentamicin; he was then treated with
      oral cefixime. A second patient was treated with IV ceftriaxone, administered at
      the DTC once culture results were available, and remained febrile for <72 hours.
      The last 2 patients were hospitalized; one, who was also allergic to
      cephalosporins, had been febrile for 72 hours at the time of hospitalization
      (once hospitalized, he was treated with IV amikacin), and the other was admitted
      to the hospital for an unrelated problem, namely, scalp cellulitis. None of these
      4 patients was initially bacteremic or became bacteremic during the treatment
      period. Repeat urine culture was performed within 14 days after treatment
      initiation in 146 instances, and results were negative in all cases. At telephone
      follow-up assessments 14 days after discharge, no patient had been rehospitalized
      because of UTI. Successful treatment at the DTC (defined as attendance at all
      visits, normalization of temperature within 96 hours, negative control urine
      cultures, if performed, and absence of hospitalization from the DTC) was observed
      in 96.6% of the 178 UTI episodes. Overall adherence of physicians to the protocol
      at the DTC was 87.1% (95% confidence interval: 82.2-92.0%). One hundred seventy
      two satisfaction questionnaires were returned and revealed good, very good, or
      excellent parental satisfaction in 98.8% of cases. CONCLUSIONS: Our data show
      that ambulatory treatment with IV antibiotics, at a DTC, may be used for at least
      three-fourths of UTIs among febrile children 3 months to 5 years of age. It is
      safe and feasible and appears very satisfactory to parents. Although ambulatory
      treatment with IV antibiotics is more invasive than oral therapy during the
      initiation of UTI treatment, it ensures almost full compliance, allows close
      medical supervision, and facilitates investigations related to the UTI. It is an
      interesting alternative to hospitalization.

PMID- 15466074
TI  - Meeting the needs of parents around the time of diagnosis of disability among
      their children: evaluation of a novel program for information, support, and
      liaison by key workers.
AB  - OBJECTIVE: Key worker programs for families of children with disabilities, to
      promote information provision, emotional support, and liaisons among different
      agencies, have long been advocated but not extensively implemented. We report the
      impact on the experiences of parents and the practices of health care
      professionals of a novel, hospital-based, key worker service (Community Link Team
      [CLT]), implemented in the pediatric ophthalmology department of Great Ormond
      Street Hospital (London, United Kingdom). DESIGN, SETTING, AND PARTICIPANTS: The
      CLT included 2 members, 1 of whom was present during the first outpatient
      assessment by the consultant ophthalmologist of any child newly diagnosed as
      visually impaired (corrected acuity of 6/18 or worse in the better eye) and
      accompanied the family during other assessments performed during that visit. A
      dedicated room was used by the CLT members to spend time with each family after
      completion of the clinical assessments. The CLT members reiterated and/or
      clarified clinical information already provided, specifically advised the
      families about visual stimulation programs and the benefits and purpose of visual
      impairment certification, and provided information about educational and social
      services. The same CLT member met the family at subsequent visits to the
      department and acted as the first point of contact for parents. Parents of
      children newly diagnosed with visual impairment and/or ophthalmic disorders at
      Great Ormond Street Hospital participated in a 2-stage study to assess their
      needs, their views about the processes of care, and their overall satisfaction.
      The study included a questionnaire survey with 2 standard instruments, ie, the
      Measure of Processes of Care, specifically developed and used to assess parents'
      views of the degree to which health services for a range of childhood disorders
      are family-centered, and the short form of the Client Satisfaction Questionnaire,
      used to assess overall parental satisfaction or dissatisfaction with services in
      the preceding year, as in other studies of parental satisfaction with pediatric
      services. This was followed by in-depth individual interviews with a subsample of
      parents who returned completed questionnaires. The views of families with
      experience with the new service (CLT) were compared with those without. The
      experiences of health care professionals before and after implementation of the
      service were elicited through group interviews and were compared. We recognized
      that any differences would be attributable to both the direct effects of the CLT,
      ie, actual services provided by the team, and indirect effects, ie, broader
      changes in approaches or practices within the department resulting from shifting
      roles and responsibilities regarding specific elements of management. Therefore,
      both the specific tasks/activities undertaken by the CLT and broader changes in
      practices within the department were identified. RESULTS: Seventy-nine families
      from the pre-CLT group and 68 from the post-CLT group (68% and 65% of those
      invited, respectively) participated in the questionnaire survey, of which 29 and
      19 (71% and 79% of those invited), respectively, took part in interviews. The 2
      groups were comparable with respect to sociodemographic and clinical
      characteristics. Parents and health care professionals agreed that the CLT
      provided important information and facilitated access to specific services, while
      providing both emotional and social support and facilitating meetings with other
      families with children with similar conditions. A number of key generic
      components of the service were identified. First, provision, within the
      outpatient setting, of a dedicated "quiet room" and office space for key workers
      was an essential physical requirement. Second, early identification of the key
      workers as the parents' point of contact was essential; this was achieved in this
      case by the CLT members attending the first consultation, combined with their
      detailed debriefing of families at the end of the outpatient visit. Third, the
      adoption of certain tasks by the key workers, including some previously
      undertaken by ophthalmologists, helped to define the liaison role of the program.
      These tasks included discussing the process and benefits of visual impairment
      certification, contacting the advisory teacher for the visually impaired, and
      providing written reports to educational and social services; analogous tasks
      would exist for other disabilities. CONCLUSIONS: Research on the needs of
      families of visually impaired children has been limited but indicates that, as
      with other childhood disabilities, the greatest needs during the critical period
      around diagnosis are for information, especially about educational and social
      services, and emotional support from professionals, informal and formal social
      networks, and support groups. Although not widely implemented or studied, key
      worker programs for families of visually impaired children, particularly in the
      context of multidisciplinary visual impairment teams, have been advocated, on the
      basis of their potential to facilitate coordination of health, educational, and
      social services. The model of such provision evaluated in this study reflects the
      fact that it was established as an outpatient service in a tertiary referral
      center for pediatric ophthalmology in the United Kingdom, with the specific
      structure and specialized roles for health care professionals that this requires.
      Different models might be more suitable in other settings in the United Kingdom
      or elsewhere. However, the important general lessons learned should guide
      implementation of such services for families of children with other disabilities.
      The recently launched National Service Framework for Children provides a new
      context and standards for meeting the needs of disabled children and their
      families in the United Kingdom and may also guide initiatives elsewhere. The
      findings of this study support implementation of programs for information
      provision, support, and liaison by key workers in all specialized centers for the
      assessment and diagnosis of children with serious visual problems. Implementation
      of similar services for families with children with other disabilities is likely
      to be equally valuable.

PMID- 15466075
TI  - A systematic review of interventions to prevent childhood farm injuries.
AB  - OBJECTIVE: The goal of the study was to systematically review the global body of
      evidence surrounding the effectiveness of interventions for the prevention of
      acute pediatric agricultural injuries. A specific focus was the effectiveness of
      the North American Guidelines for Children's Agricultural Tasks. METHODS: Two
      reviewers independently screened studies and applied inclusion criteria on the
      basis of searches of 17 bibliographic databases (eg, Medline and Embase). We also
      screened reference lists of relevant studies and contacted experts in the area.
      Studies were included if they represented primary research, a comparison group
      was used, the study population included children or the intervention was directly
      applicable to children, and objective outcomes were reported. Two reviewers
      independently assessed the methodologic quality of included studies with the
      Downs and Black checklist. A qualitative analysis was performed because of
      extensive heterogeneity among studies. RESULTS: We included 23 controlled
      studies, ie, 4 randomized, controlled trials, 5 controlled trials, and 14
      quasiexperimental or observational studies. Only 8 of the relevant studies were
      published in peer-reviewed journals. School-based programs appeared to be
      effective at increasing short-term knowledge acquisition; outcomes were enhanced
      with active, hands-on participation, as opposed to passive activities. Safety day
      camps showed positive results for knowledge acquisition. Tractor training
      programs and community- and farm-based interventions showed mixed results.
      Studies examining the North American Guidelines for Children's Agricultural Tasks
      suggested that uptake improves if dissemination is accompanied by a farm visit
      from a safety specialist or if information about child development principles is
      provided in conjunction with the guidelines. CONCLUSIONS: There is a lack of
      randomized, controlled trials and community-based trials in this area. Studies
      primarily examined intermediate outcomes, such as knowledge acquisition; few
      studies evaluated changes in injury rates. The interventions targeted at children
      and youths that were evaluated focused on educational interventions. There is
      both the need and potential for the development and evaluation of injury control
      interventions for children, particularly programs addressing lethal injuries to
      young/preschool-aged children.

PMID- 15466076
TI  - Maternal smoking and infantile gastrointestinal dysregulation: the case of colic.
AB  - BACKGROUND: Infants' healthy growth and development are predicated, in part, on
      regular functioning of the gastrointestinal (GI) tract. In the first 6 months of
      life, infants typically double their birth weights. During this period of intense
      growth, the GI tract needs to be highly active and to function optimally.
      Identifying modifiable causes of GI tract dysregulation is important for
      understanding the pathophysiologic processes of such dysregulation, for
      identifying effective and efficient interventions, and for developing early
      prevention and health promotion strategies. One such modifiable cause seems to be
      maternal smoking, both during and after pregnancy. Purpose. This article brings
      together information that strongly suggests that infants' exposure to tobacco
      smoke is linked to elevated blood motilin levels, which in turn are linked to an
      increased risk of GI dysregulation, including colic and acid reflux. We base this
      hypothesis on evidence supporting a link between maternal smoking and infantile
      colic (IC) and on additional evidence proposing increased motilin release,
      attributable to exposure to tobacco smoke and its metabolites, as a physiologic
      mechanism linking maternal smoking with infantile GI dysregulation. METHODS: We
      critically review and synthesize epidemiologic, physiologic, and biological
      evidence pertaining to smoking and colic, smoking and motilin levels, and motilin
      and colic. RESULTS: Six studies have investigated the link between maternal
      smoking and IC, but IC was defined according to Wessel's rule of threes (crying
      for > or =3 hours per day, > or =3 days per week, for > or =3 weeks) in only 1 of
      these studies. The remaining studies used definitions that ranged from less
      stringent variations of Wessel's criteria to definitions that would suggest
      excessive crying but not necessarily colic. Results from 5 of these studies
      suggest that there is an independent association between maternal smoking and
      excessive crying, as well as IC. Recent studies of the GI system provide strong,
      but indirect, corroborating evidence suggesting physiologic pathways through
      which maternal smoking can be linked to IC. This physiologic evidence can be
      outlined as follows: (1) smoking is linked to increased plasma and intestinal
      motilin levels and (2) higher-than-average levels of motilin are linked to
      elevated risks of IC. Although these findings from disparate fields suggest a
      physiologic mechanism linking maternal smoking with IC, the entire chain of
      events has not been examined in a single cohort. A prospective study, begun in
      pregnancy and continuing through the first 4 months of life, could provide
      definitive evidence linking these disparate lines of research. Key points for
      such a study are considered. CONCLUSIONS: New epidemiologic evidence suggests
      that exposure to cigarette smoke and its metabolites may be linked to IC.
      Moreover, studies of the GI system provide corroborating evidence that suggests
      that (1) smoking is linked to increased plasma and intestinal motilin levels and
      (2) higher-than-average intestinal motilin levels are linked to elevated risks of
      IC. In the United States, nearly one-half of all women smokers continue to smoke
      during their pregnancies. This amounts to approximately 12% of all women who give
      birth. Moreover, it is estimated that 50% to 80% of employed adults have regular
      exposure to environmental tobacco smoke and that >30% of nonsmokers live with
      smokers. If, as we suspect, exposure to cigarette smoke increases the risk of
      colic, then this would provide additional incentives to parents to abstain from
      smoking. Decreased exposure to tobacco smoke can be expected to provide
      widespread and long-term health benefits to maternal and child populations.

PMID- 15466077
TI  - The sudden infant death syndrome gene: does it exist?
AB  - BACKGROUND: Sudden infant death syndrome (SIDS) is in a difficult position
      between the legal and medical systems. In the United Kingdom, prosecutors have
      for years applied the simple rule that 1 unexpected death in a family is a
      tragedy, 2 are suspicious, and 3 are murder. However, it seems that the pendulum
      has now swung to the opposite extreme; mutations or polymorphisms with unclear
      biological significance are accepted in court as possible causes of death. This
      development makes research on genetic predisposing factors for SIDS increasingly
      important, from the standpoint of the legal protection of infants. The genetic
      component of sudden infant death can be divided into 2 categories, ie (1)
      mutations that give rise to genetic disorders that constitute the cause of death
      by themselves and (2) polymorphisms that might predispose infants to death in
      critical situations. Distinguishing between these 2 categories is essential, and
      cases in which a mutation causing a lethal genetic disorder is identified should
      be diagnosed not as SIDS but as explained death. GENETIC ALTERATIONS THAT MAY
      CAUSE SUDDEN INFANT DEATH: Deficiencies in fatty acid metabolism have been
      extensively studied in cases of SIDS, and by far the most well-investigated
      mutation is the A985G mutation in the medium-chain acyl-CoA dehydrogenase (MCAD)
      gene, which is the most prevalent mutation causing MCAD deficiency. However, <1%
      of sudden infant death cases investigated have this mutation, and findings of
      biochemical profiles seen in specific fatty acid oxidation disorders in a number
      of such cases emphasize the importance of investigating fatty acid oxidation
      disorders other than MCAD deficiency. Severe acute hypoglycemia may cause sudden
      death among infants, but only rare novel polymorphisms have been found when key
      proteins involved in the regulation of blood glucose levels are investigated in
      cases of SIDS. The long QT syndrome (LQTS) is another inherited condition
      proposed as the cause of death in some cases of sudden infant death. The LQTS is
      caused by mutations in genes encoding cardiac ion channels, and mutations in the
      genes KVLQT1 and SCNA5 have been identified in cases initially diagnosed as SIDS,
      in addition to several polymorphisms in these 2 genes and in the HERG gene. In
      addition, genetic risk factors for thrombosis were investigated in a small number
      of SIDS cases; the study concluded that venous thrombosis is not a major cause of
      sudden infant death. GENE POLYMORPHISMS THAT MAY PREDISPOSE INFANTS TO SUDDEN
      INFANT DEATH UNDER CERTAIN CIRCUMSTANCES: Many SIDS victims have an activated
      immune system, which may indicate that they are vulnerable to simple infections.
      One reason for such vulnerability may be partial deletions of the complement
      component 4 gene. In cases of SIDS, an association between slight infections
      before death and partial deletions of the complement component 4 gene has been
      identified, which may indicate that this combination represents increased risk of
      sudden infant death. There have been a few studies investigating HLA-DR genotypes
      and SIDS, but no association has been demonstrated. The most common polymorphisms
      in the interleukin-10 (IL-10) gene promoter have been investigated in SIDS cases,
      and the ATA/ATA genotype has been reported to be associated with both SIDS and
      infectious death. The findings may indicate that, in a given situation, an infant
      with an unfavorable IL-10 genotype may exhibit aberrant IL-10 production, and
      they confirm the assumption that genes involved in the immune system are of
      importance with respect to sudden unexpected infant death. Another gene that has
      been investigated is the serotonin transporter gene, and an association between
      the long alleles of this gene and SIDS has been demonstrated. Serotonin
      influences a broad range of physiologic systems, as well as the interactions
      between the immune and nervous systems, and findings of decreased serotonergic
      binding in parts of the brainstem, together with the findings in the serotonin
      transporter gene, may indicate that serotonin plays a regulatory role in SIDS. It
      has also been speculated that inadequate thermal regulation is involved in SIDS,
      but investigations of genes encoding heat-shock proteins and genes encoding
      proteins involved in lipolysis from brown adipose tissue have not found evidence
      of linkages between common polymorphisms in these genes and SIDS. A number of
      human diseases are attributable to mutations in mitochondrial DNA (mtDNA), and
      there are several reasons to think that mtDNA mutations also are involved in
      SIDS. Both a higher substitution frequency and a different substitution pattern
      in the HVR-I region of mtDNA have been reported in SIDS cases, compared with
      control cases. A number of coding region mtDNA mutations have also been reported,
      but many are found only in 1 or a few SIDS cases, and, to date, no predominant
      mtDNA mutation has been found to be associated with SIDS. CONCLUSIONS: All
      mutations giving rise to metabolic disorders known to be associated with life
      threatening events are possible candidates for genes involved in cases of sudden
      infant death, either as a cause of death or as a predisposing factor. It is
      necessary to distinguish between lethal mutations leading to diseases such as
      MCAD and LQTS, and polymorphisms (for instance, in the IL-10 gene and mtDNA) that
      are normal gene variants but might be suboptimal in critical situations and thus
      predispose infants to sudden infant death. It is unlikely that one mutation or
      polymorphism is the predisposing factor in all SIDS cases. However, it is likely
      that there are "SIDS genes" operating as a polygenic inheritance predisposing
      infants to sudden infant death, in combination with environmental risk factors.
      For genetically predisposed infants, a combination of, for instance, a slight
      infection, a prone sleeping position, and a warm environment may trigger a
      vicious circle with a death mechanism, including hyperthermia, irregular
      breathing, hypoxemia, and defective autoresuscitation, eventually leading to
      severe hypoxia, coma, and death.

PMID- 15466078
TI  - Paraneoplastic autoimmune multiorgan syndrome (paraneoplastic pemphigus) in a
      child: case report and review of the literature.
AB  - Paraneoplastic autoimmune multiorgan syndrome, also known as paraneoplastic
      pemphigus, has been observed only rarely among children. We describe a 10-year
      old boy with typical clinical and histologic findings of paraneoplastic pemphigus
      associated with Castleman's disease. His disease was refractory to resection of
      the tumor and aggressive combination immunosuppressive therapies. The patient
      died 1 year after presentation, as a result of complications of bronchiolitis
      obliterans. This case is unusual because of the young age of the patient.

PMID- 15466079
TI  - Life-threatening human metapneumovirus pneumonia requiring extracorporeal
      membrane oxygenation in a preterm infant.
AB  - We present the first report in the literature of a child with human
      metapneumovirus pneumonia who required extracorporeal membrane oxygenation for
      survival. This was a 3-month-old premature boy from British Columbia, Canada, who
      developed severe respiratory failure, experienced failure of high-frequency
      oscillatory mechanical ventilation, and required extracorporeal membrane
      oxygenation support for 10 days. This case illustrates the importance of
      including this newly discovered pathogen among the causes of childhood pneumonia.

PMID- 15466080
TI  - Laparoscopic diagnosis and cure of hyperinsulinism in two cases of focal
      adenomatous hyperplasia in infancy.
AB  - Persistent hyperinsulinemic hypoglycemia of infancy or congenital hyperinsulinism
      of the neonate is a rare condition that may cause severe neurologic damage if the
      disease is unrecognized or inadequately treated. Current treatment aims to
      restore normal blood glucose levels by providing a carbohydrate-enriched diet and
      drugs that inhibit insulin secretion. If medical treatment fails, then surgery is
      required. Because congenital hyperinsulinism may be caused either by diffuse
      involvement of pancreatic beta-cells or by a focal cluster of abnormal beta
      cells, the extent of pancreatectomy varies. We report on 2 patients with a focal
      form of the disease for whom diagnosis was made with laparoscopy. Laparoscopic
      enucleation of the lesion was curative.

PMID- 15466081
TI  - Developmental outcomes with early orthotopic liver transplantation for infants
      with neonatal-onset urea cycle defects and a female patient with late-onset
      ornithine transcarbamylase deficiency.
AB  - Urea cycle defects (UCDs) typically present with hyperammonemia, the duration and
      peak levels of which are directly related to the neurologic outcome. Liver
      transplantation can cure the underlying defect for some conditions, but the
      preexisting neurologic status is a major factor in the final outcome. Multicenter
      data indicate that most of the children who receive transplants remain
      significantly neurologically impaired. We wanted to determine whether aggressive
      metabolic management of ammonia levels after early referral/transfer to a
      metabolism center and early liver transplantation would result in better
      neurologic outcomes. We report on 5 children with UCDs, ie, 2 male patients with
      X-linked ornithine transcarbamylase deficiency and 2 male patients with carbamoyl
      phosphate synthase deficiency, all of whom had neonatal presentations and
      underwent orthotopic liver transplantation before 1 year of age, and 1 female
      patient with partial X-linked ornithine transcarbamylase deficiency that was
      intractable to medical therapy, who underwent transplantation at 35 months of
      age. Developmental testing with the Griffiths scale was performed on 3 occasions
      each, 12 months apart, up to 45 months after transplantation. Full-scale indices
      for 3 children who underwent early transplantation showed average developmental
      quotients of 67. All 5 children had metabolic cures. There were no deaths (30
      month survival rate: 100%). One child is currently listed for repeat
      transplantation because of bile duct stenosis and cirrhosis. We conclude that
      early liver transplantation and aggressive metabolic management improve early
      neurologic outcomes for children with UCDs, but longer follow-up monitoring is
      needed.

PMID- 15466082
TI  - Presacral neuroenteric fistula in a newborn presenting with an epidural abscess:
      case report and review of the literature.
AB  - We describe a newborn infant (<24 hours of age) who presented with mild swelling
      on the back and buttocks attributable to a neuroenteric fistula complicated by an
      epidural parasacral abscess infected with mixed coliforms. Epidural abscesses in
      infancy are extremely rare, and one has not been observed previously in the
      newborn period. The infant was surprisingly mildly affected. Prompt intervention
      led to an excellent outcome. Coliforms may colonize the infant gut in <24 hours,
      even in the developed world. Unexplained swellings on the backs of infants should
      lead to a search for underlying malformations and an early surgical review, which
      is best conducted with a combined pediatric surgical and neurosurgical approach.

PMID- 15466083
TI  - Nephrotic syndrome complicating alpha-glucosidase replacement therapy for Pompe
      disease.
AB  - We report a patient with Pompe disease who developed reversible nephrotic
      syndrome during prolonged, high-dose, experimental, enzyme replacement therapy
      with recombinant human acid alpha-glucosidase (rhGAA). Because of the development
      of antibodies to rhGAA and concomitant clinical decline, escalating doses of
      rhGAA were administered as part of an experimental immune tolerance regimen.
      Histologic evaluation of kidney tissue revealed glomerular deposition of immune
      complexes containing rhGAA itself, in a pattern of membranous nephropathy. To our
      knowledge, this is the first reported case of nephrotic syndrome occurring during
      enzyme replacement therapy. The nephrotic syndrome gradually resolved after the
      rhGAA dose was decreased, indicating that decreasing the antigenic load can
      ameliorate glomerular immune complex deposition associated with enzyme
      replacement in a highly sensitized patient.

PMID- 15466084
TI  - Newborn screening for lysosomal storage disorders: clinical evaluation of a two
      tier strategy.
AB  - OBJECTIVE: To evaluate the use of protein markers using immune-quantification
      assays and of metabolite markers using tandem mass spectrometry for the
      identification, at birth, of individuals who have a lysosomal storage disorder.
      METHODS: A retrospective analysis was conducted of Guthrie cards that were
      collected from newborns in Denmark during the period 1982-1997. Patients whose
      lysosomal storage disorder (LSD; 47 representing 12 disorders) was diagnosed in
      Denmark during the period 1982-1997 were selected, and their Guthrie cards were
      retrieved from storage. Control cards (227) were retrieved from the same period.
      Additional control cards (273) were collected from the South Australian Screening
      Centre (Australia). RESULTS: From 2 protein and 94 metabolite markers, 15 were
      selected and evaluated for their use in the identification of LSDs.
      Glycosphingolipid and oligosaccharide markers showed 100% sensitivity and
      specificity for the identification of Fabry disease, alpha-mannosidosis,
      mucopolysaccharidosis (MPS) IVA, MPS IIIA, Tay-Sachs disease, and I-cell disease.
      Lower sensitivities were observed for Gaucher disease and sialidosis. No useful
      markers were identified for Krabbe disease, MPS II, Pompe disease, and Sandhoff
      disease. The protein markers LAMP-1 and saposin C were not able to differentiate
      individuals who had an LSD from the control population. CONCLUSIONS: Newborn
      screening for selected LSDs is possible with current technology. However,
      additional development is required to provide a broad coverage of disorders in a
      single, viable program.

PMID- 15466085
TI  - Cost-effectiveness of strategies that are intended to prevent kernicterus in
      newborn infants.
AB  - OBJECTIVE: There is concern about an increasing incidence of kernicterus in
      healthy term neonates in the United States. Although the incidence of kernicterus
      is unknown, several potential strategies that are intended to prevent kernicterus
      have been proposed by experts. It is necessary to assess the costs, benefits, and
      risks of such strategies before widespread policy changes are made. The objective
      of this study was to determine the direct costs to prevent a case of kernicterus
      with the following 3 strategies: (1) universal follow-up in the office or at home
      within 1 to 2 days of early newborn discharge, (2) routine predischarge serum
      bilirubin with selective follow-up and laboratory testing, and (3) routine
      predischarge transcutaneous bilirubin with selective follow-up and laboratory
      testing. METHODS: We performed an incremental cost-effectiveness analysis of the
      3 strategies compared with current practice. We used a decision analytic model
      and a spreadsheet to estimate the direct costs and outcomes, including the
      savings resulting from prevented kernicterus, for an annual cohort of 2,800000
      healthy term newborns who are eligible for early discharge. We used a modified
      societal perspective and 2002 US dollars. With each strategy, the test and
      treatment thresholds for hyperbilirubinemia are lowered compared with current
      practice. RESULTS: With the base-case assumptions (current incidence of
      kernicterus 1:100 000 and a relative risk reduction [RRR] of 0.7 with each
      strategy), the cost to prevent 1 case of kernicterus was 10,321463 dollars,
      5,743905 dollars, and 9,191352 dollars respectively for strategies 1, 2, and 3
      listed above. The total annual incremental costs for the cohort were,
      respectively, 202,300671 dollars, 112,580535 dollars, and 180,150494 dollars.
      Sensitivity analyses showed that the cost per case is highly dependent on the
      population incidence of kernicterus and the RRR with each strategy, both of which
      are currently unknown. In our model, annual cost savings of 46,179465 dollars for
      the cohort would result with strategy 2, if the incidence of kernicterus is high
      (1:10,000 births or higher) and the RRR is high (> or =0.7). If the incidence is
      lower or the RRR is lower, then the cost per case prevented ranged from 4,145676
      dollars to as high as 77,650240 dollars. CONCLUSIONS: Widespread implementation
      of these strategies is likely to increase health care costs significantly with
      uncertain benefits. It is premature to implement routine predischarge serum or
      transcutaneous bilirubin screening on a large scale. However, universal follow-up
      may have benefits beyond kernicterus prevention, which we did not include in our
      model. Research is required to determine the epidemiology, risk factors, and
      causes of kernicterus; to evaluate the effectiveness of strategies intended to
      prevent kernicterus; and to determine the cost per quality-adjusted life year
      with any proposed preventive strategy.

PMID- 15466086
TI  - Clinical spectrum, morbidity, and mortality in 113 pediatric patients with
      mitochondrial disease.
AB  - OBJECTIVES: The aim of this study was to elucidate the frequency of major
      clinical manifestations in children with mitochondrial disease and establish
      their clinical course, prognosis, and rates of survival depending on their
      clinical features. METHODS: We performed a retrospective review of the medical
      records of 400 patients who were referred for evaluation of mitochondrial
      disease. By use of the modified Walker criteria, only patients who were assigned
      a definite diagnosis were included in the study. RESULTS: A total of 113
      pediatric patients with mitochondrial disease were identified. A total of 102
      (90%) patients underwent a muscle biopsy as part of the diagnostic workup. A
      significant respiratory chain (RC) defect, according to the diagnostic criteria,
      was found in 71% of the patients who were evaluated. In this cohort, complex I
      deficiency (32%) and combined complex I, III, and IV deficiencies (26%) were the
      most common causes of RC defects, followed by complex IV (19%), complex III
      (16%), and complex II deficiencies (7%). Pathogenic mitochondrial DNA
      abnormalities were found in 11.5% of the patients. A substantial fraction (40%)
      of patients with mitochondrial disorders exhibited cardiac disease, diagnosed by
      Doppler echocardiography; however, the majority (60%) of patients had predominant
      neuromuscular manifestations. No correlation between the type of RC defect and
      the clinical presentation was observed. Overall, the mean age at presentation was
      40 months. However, the mean age at presentation was 33 months in the cardiac
      group and 44 months in the noncardiac group. Twenty-six (58%) patients in the
      cardiac group exhibited hypertrophic cardiomyopathy, 29% had dilated
      cardiomyopathy, and the remainder (13%) had left ventricular noncompaction.
      Patients with cardiomyopathy had an 18% survival rate at 16 years of age.
      Patients with neuromuscular features but no cardiomyopathy had a 95% survival at
      the same age. CONCLUSIONS: This study gives strong support to the view that in
      patients with RC defects, cardiomyopathy is more common than previously thought
      and tends to follow a different and more severe clinical course. Although with a
      greater frequency than previously reported, mitochondrial DNA mutations were
      found in a minority of patients, emphasizing that most mitochondrial disorders of
      childhood follow a Mendelian pattern of inheritance.

PMID- 15466087
TI  - Behavioral outcomes and evidence of psychopathology among very low birth weight
      infants at age 20 years.
AB  - OBJECTIVE: Information on the mental health of very low birth weight (VLBW; <1500
      g) children in young adulthood is sparse. We thus sought to examine gender
      specific behavioral outcomes and evidence of psychopathology in a cohort of VLBW
      young adults at 20 years of age. METHODS: We compared a cohort of 241 survivors
      among VLBW infants who were born between 1977 and 1979 (mean birth weight: 1180
      g; mean gestational age at birth: 29.7 weeks), 116 of whom were men and 125 of
      whom were women, with 233 control subjects from the same population in Cleveland
      who had normal birth weights (108 men and 124 women). Young adult behavior was
      assessed at 20 years of age with the Achenbach Young Adult Self-Report and the
      Young Adult Behavior Checklist for parents. In addition, the young adults and
      parents completed the ADHD Rating Scale for Adults. Gender-specific outcomes were
      adjusted for sociodemographic status. RESULTS: VLBW men reported having
      significantly fewer delinquent behaviors than normal birth weight (NBW) control
      subjects, but there were no differences on the Internalizing, Externalizing, or
      Total Problem Behavior scales. Parents of VLBW men reported significantly more
      thought problems for their sons than did parents of control subjects. VLBW women
      reported significantly more withdrawn behaviors and fewer delinquent behavior
      problems than control subjects. Their rates of internalizing behaviors (which
      includes anxious/depressed and withdrawn behaviors) above the borderline clinical
      cutoff were 30% versus 16% (odds ratio: 2.2; 95% confidence interval [CI]: 1.2
      4.1). Parents of VLBW women reported significantly higher scores for their
      daughters on the anxious/depressed, withdrawn, and attention problem subscales
      compared with control parents. The odds ratios for parent-reported rates above
      the borderline-clinical cutoff among women for the anxious/depressed subscale was
      4.4 (95% CI: 1.4-13.5), for thought problems was 3.7 (95% CI: 1.2-11.6), and for
      attention problems was 2.4 (95% CI: 1.0-5.5). There were no differences in the
      young adult self-report of attention-deficit/hyperactivity disorder (ADHD).
      Parents of VLBW men reported higher mean scores on the attention subtype of ADHD
      but not higher rates of ADHD. CONCLUSION: The increase in psychopathology among
      VLBW survivors in young adulthood indicates a need for anticipatory guidance and
      early intervention that might help to prevent or ameliorate potential
      psychopathology.

PMID- 15466088
TI  - Does interleukin-6 genotype influence cerebral injury or developmental progress
      after preterm birth?
AB  - OBJECTIVE: The severity of the proinflammatory response may determine outcome in
      the critically ill. Genetic variation in the promoter region of the gene encoding
      the proinflammatory cytokine interleukin-6 (IL-6; -174 CC genotype) may encode
      enhanced production of IL-6. Our objective was to determine whether the CC
      genotype is associated with worse early illness severity, neurologic injury, and
      lower developmental scores among surviving preterm children. METHODS: Genotype
      was determined from dried blood spots that were taken for neonatal screening
      tests 7 days or more after birth; outcome was independently assessed as part of a
      longitudinal study of children of < or =32 weeks' gestational age. RESULTS: CC
      genotype was associated with worse intensive care indices. Significant
      hemorrhagic brain injuries occurred in 5 (19%) of 27 children with CC genotype
      compared with 7 (6%) of 121 children with GC or GG genotype, and images
      consistent with white matter damage (ventriculomegaly or cystic periventricular
      leukomalacia) occurred in 9 (26%) of CC patients compared with 9 (7%) in GC/GG
      children. Disability occurred significantly more often in CC children: 8 (31%)
      compared with 16 (13%). A similar trend was also noted in children with cerebral
      palsy (15% compared with 7%, respectively). Developmental, cognitive, and motor
      scores at 2 years and 5.5 years were independent of genotype among children with
      or without disability. CONCLUSIONS: In a population of surviving children who
      were born at < or =32 weeks' gestational age, variation of the gene that may
      increase IL-6 synthesis is associated with disabling brain injury but not
      cognitive development despite association with worse early critical care indices.

PMID- 15466089
TI  - Change in recommendation affects influenza vaccinations among children 6 to 59
      months of age.
AB  - OBJECTIVE: To evaluate the impact of the 2002-2003 recommendation to "encourage
      when feasible" the influenza vaccine for healthy children 6 to 23 months of age.
      METHODS: A cross-sectional study of children who were 6 to 59 months of age and
      presented to a large, pediatric resident's continuity clinic or the affiliated
      acute care clinic in the summers of 2002 and 2003 was performed. The influenza
      vaccination status of children in the winter before enrollment and factors that
      influenced this status were determined by parental questionnaire. RESULTS: Of 245
      and 329 children in the 2002 and 2003 study populations, influenza vaccinations
      increased from 7% to 18%, respectively. For healthy children 6 to 23 months of
      age, influenza vaccinations increased from 1% in 2002 to 17% in 2003 and
      accounted for most of the increase seen in the study population. Multivariate
      analysis revealed that the strongest predictor of pediatric influenza vaccination
      was parental recall of a physician recommendation (odds ratio: 39.3; 95%
      confidence interval: 17.3-89.4 in 2003). However, 65% of parents of high-risk
      children did not recall a physician recommendation despite the fact that the
      influenza vaccine was recommended for high-risk patients during both study years.
      CONCLUSION: Concomitant with the 2002-2003 influenza vaccine recommendation for
      healthy children 6 to 23 months of age, influenza vaccinations for these children
      increased significantly. Because most children for whom the influenza vaccine was
      recommended were not vaccinated, physicians have the opportunity to increase the
      pediatric influenza vaccination rate by improving their recommendation
      strategies.

PMID- 15466090
TI  - Features of invasive staphylococcal disease in neonates.
AB  - OBJECTIVE: Most clinical descriptions of invasive staphylococcal disease (ISD) in
      neonates date from before the mid-1980s, when neonatal viability and intensive
      care differed substantially from current standards. We aimed to describe the
      contemporary incidence, clinical features, and outcome of infants with ISD in a
      neonatal intensive care unit. METHODS: A retrospective cohort study was conducted
      of infants who had ISD and were in the neonatal intensive care unit of the
      Woman's Hospital of Texas, Houston, from January 2000 to June 2002. Confirmed ISD
      was defined as clinical sepsis and Staphylococcus aureus (SA) isolated from > or
      =1 blood culture (BC) or a sterile body site excluding urine or coagulase
      negative staphylococci (CoNS) isolated from > or =2 BC or from 1 BC and a sterile
      body site. Probable ISD was defined as CoNS isolated from 1 BC or a sterile body
      site for which clinical and laboratory data review by 3 infectious disease
      specialists indicated that antimicrobial treatment was appropriate. Confirmed and
      combined confirmed plus probable cases were analyzed. RESULTS: A total of 149
      episodes (83 confirmed [39 SA, 44 CoNS], 66 probable) in 137 infants (mean
      gestational age [GA]: 27.6 weeks [22.4-36.4]; mean birth weight: 981 g [350
      2995]) were reviewed. Four (3%) infants had early-onset infection (2 SA, 2 CoNS).
      Median age at infection onset was similar (17 days SA; 18 days CoNS).
      Intravascular catheters (IVC) were in situ in a minority of infants with ISD
      episodes (38% SA, 43% CoNS). CoNS more than SA infections were associated with
      very low birth weight (<1500 g), lower GA, a history of more IVCs and concurrent
      total parenteral nutrition, but IVC and parenteral nutrition days were similar.
      By multivariate analysis correcting for birth weight and complications of
      prematurity, hypoxia at the time of sepsis evaluation was significantly
      associated with CoNS and hypotension with SA infections; other clinical features
      were similar. Methicillin-resistant SA caused 8% of SA infections. Among
      bacteremic infants, SA more frequently than CoNS involved > or =2 sites. Overall,
      SA had more focal complications (primarily bone and joint) than CoNS, resulting
      in a 2- to 3-fold higher SA-associated morbidity rate. Mortality directly
      attributable to either organism was similar (5% SA; 5% confirmed, 3%
      confirmed/probable CoNS). CONCLUSION: CoNS ISD occurred in smaller, more
      premature infants than SA and was IVC associated in a minority of cases. Hypoxia
      and hypotension were the only presenting features that differentiated CoNS and
      SA. SA-associated morbidity was substantial, but SA infection carried no greater
      risk of death (5%) than CoNS.

PMID- 15466091
TI  - Which characteristics of children with a febrile seizure are associated with
      subsequent physician visits?
AB  - OBJECTIVE: To reanalyze an existing data set to determine which children with an
      initial febrile seizure have excessive subsequent physician visits. METHODS:
      Individual data from a regional cohort of 75 children with a first febrile
      seizure and 150 febrile and 150 afebrile control subjects were linked to a
      comprehensive physician services database. The impact of study variables on
      subsequent physician utilization over the following 6 years was modeled using
      analysis of variance. RESULTS: Children with a known family history of febrile
      seizures at the time of study entry had 24% fewer physician visits. Control
      children with a known family history of afebrile seizures had 7% fewer visits
      than those with negative family histories. Children with an initial febrile
      seizure had 45% more physician visits when they knew of a relative with afebrile
      seizures than those with negative family histories. CONCLUSIONS: Knowing the
      family history of seizures is probably a marker of reduced physician utilization.
      At the time of an initial febrile seizure, knowing the family history of afebrile
      seizures defines a group of patients with excessive subsequent physician visits.

PMID- 15466092
TI  - Clinical redesign using all patient refined diagnosis related groups.
AB  - OBJECTIVE: Clinical redesign of processes in hospitals that care for children has
      been limited by a paucity of severity-adjusted indicators that are sensitive
      enough to identify areas of concern. This is especially true of hospitals that
      analyze pediatric patient care using standard Centers for Medicare and Medicaid
      Services (CMS) diagnosis-related groups (DRGs). The objectives of this study were
      to determine whether 1) utilization of all-patient refined (APR)-DRG severity
      adjusted indicators (length of stay, cost per case, readmission rate) from the
      National Association of Children's Hospitals and Related Institutions (NACHRI)
      database could identify areas for improvement at University of Michigan Mott
      Children's Hospital (UMMCH) and 2) hospital staff could use the information to
      implement successful clinical redesign. METHODS: The APR-DRG Classification
      System (version 20) was used with the NACHRI Case Mix Comparative Database by
      severity level comparison from 1999 to 2002. Indicators include average length of
      stay (ALOS), case mix index, cost per case, and readmission rate for low acuity
      asthma (APR-DRG 141.1). UMMCH cases of 141.1 (n = 511) were compared with NACHRI
      141.1 (n = 64,312). Although not part of the standard report, mortality rates
      were calculated by NACHRI for UMMCH and an aggregate of NACHRI member children's
      hospitals. RESULTS: Data from 1999 revealed that in noncomplicated asthma cases
      (level 1 severity), the UMMCH ALOS versus NACHRI ALOS was slightly longer (UMMCH
      2.16 days vs NACHRI 2.14 days), and the cost per case was higher (UMMCH $2824 vs
      NACHRI 2738 dollars), whereas levels 2, 3, and 4 cases (moderate, major, and
      extreme severity) indicated the ALOS and cost per case were lower than the
      national aggregate. This showed that the APR-DRG system was sensitive enough to
      distinguish variances of care within a diagnosis according to severity level.
      After analysis of internal data and meeting with clinicians to review the
      indicators, 3 separate clinical processes were targeted: 1) correct documentation
      of comorbidities and complications, 2) standardized preprinted orders were
      created with the involvement of the pediatric pulmonologists, and 3) standardized
      automatic education for parents was started on the first day of admission. Yearly
      data were reviewed and appropriate adjustments made in the education of both
      residents and staff. In 2002, the UMMCH ALOS dropped to 1.75 +/- .08 days from
      2.16 +/- .09. In 2002, the NACHRI ALOS was 2.00 days +/- 0.01 versus the UMMCH
      ALOS of 1.75 days +/- 0.0845, indicating that the UMMCH ALOS dropped
      significantly lower than the NACHRI aggregate database over the 3-year period.
      Cost per case of UMMCH compared with NACHRI after the 3 years indicated that
      UMMCH increased 12%, whereas the NACHRI aggregate increased 18%. These data show
      that length of stay and cost per case relative to the national database improved
      after clinical redesign. Improvements have been sustained throughout the 3-year
      period. Readmission rates ranged from 2.97% to 0.80% and were less than the
      national cohort by the third year. There were no mortalities in the UMMCH
      inpatient asthma program. This demonstrates that clinicians believed that the
      data from the APR-DRG acuity-adjusted system was useful and that they were then
      able to apply classical clinical redesign strategies to improve cost
      effectiveness and quality that was sustained over 3 years. CONCLUSIONS: Severity
      adjusted indicators were useful for identifying areas appropriate for clinical
      redesign and contributed to the improvement in cost-effective patient care
      without a detriment in quality indicators. This method of using a large
      comparative database, having measures of severity, and using internal analysis is
      generalizable for pediatric hospitals and can contribute to ongoing attempts to
      improve cost-effectiveness and quality in medical care.

PMID- 15466093
TI  - Plagiocephaly and brachycephaly in the first two years of life: a prospective
      cohort study.
AB  - OBJECTIVES: Although referrals for nonsynostotic plagiocephaly (NSP) have
      increased in recent years, the prevalence, natural history, and determinants of
      the condition have been unclear. The objective of this study was to assess the
      prevalence and natural history of NSP in normal infants in the first 2 years of
      life and to identify factors that may contribute to the development of NSP.
      METHODS: Two hundred infants were recruited at birth. At 6 weeks, 4 months, 8
      months, 12 months, and 2 years, the head circumference shape was digitally
      photographed, and head shape was quantified using custom-written software. At
      each age, infants were classified as cases when the cephalic index was > or =93%
      and/or the oblique cranial length ratio was > or =106%. Neck rotation and a range
      of infant, infant care, socioeconomic, and obstetric factors were assessed.
      RESULTS: Ninety-six percent of infants were followed to 12 months, and 90.5% were
      followed to 2 years. Prevalence of plagiocephaly and/or brachycephaly at 6 weeks
      and 4, 8, 12, and 24 months was 16.0%, 19.7%, 9.2%, 6.8%, and 3.3% respectively.
      The mean cephalic index by 2 years was 81.6% (range: 72.0%-102.6%); the mean
      oblique cranial length ratio was 102.6% (range: 100.1%-109.4%). Significant
      univariate risk factors of NSP at 6 weeks include limited passive neck rotation
      at birth, preferential head orientation, supine sleep position, and head position
      not varied when put to sleep. At 4 months, risk factors were male gender,
      firstborn, limited passive neck rotation at birth, limited active head rotation
      at 4 months, supine sleeping at birth and 6 weeks, lower activity level, and
      trying unsuccessfully to vary the head position when putting the infant down to
      sleep. CONCLUSIONS: There is a wide range of head shapes in infants, and
      prevalence of NSP increases to 4 months but diminishes as infants grow older. The
      majority of cases will have resolved by 2 years of age. Limited head rotation,
      lower activity levels, and supine sleep position seem to be important
      determinants.

PMID- 15466094
TI  - Externalizing problem behaviors and headache: a follow-up study of adolescent
      Finnish twins.
AB  - OBJECTIVE: To examine the association of teacher- and parent-rated behavior with
      headache in a prospective follow-up study of adolescent Finnish twins. METHODS:
      Questionnaire data were collected during 1995-2001 from a nationwide sample of
      Finnish families of 11-year-old twins who were born 1983-1987 (n = 5393) and
      again at age of 14. Psychological factors were measured by using parents' and
      teachers' ratings of a 37-item multidimensional rating instrument at the ages of
      11 and 14. RESULTS: At age 11, headache frequency (5 categories) was associated
      with total scales of externalizing and internalizing problem behaviors and
      adaptive behaviors, assessed by parents, but only with externalizing problem
      behaviors assessed by teachers. Results were similar at age 14. The incidence of
      at least monthly headache between the ages of 11 and 14 years was predicted by
      externalizing problem behaviors and 2 subscales of adaptive behaviors:
      constructiveness and poor compliance. In twin pairs discordant for headache,
      externalizing and internalizing problem behaviors were more common among headache
      sufferers than among headache-nonsufferers. Headache-discordant monozygotic co
      twins confirmed the association of externalizing problem behaviors with headache.
      CONCLUSIONS: The frequency of adolescents' headache is predicted by psychological
      factors, especially by externalizing problem behaviors. This seems to be
      independent of genetic or familial influences on behavior and headache.
      Behavioral problems may be a sign of worsening of headache or vice versa.

PMID- 15466095
TI  - Follow-up after a pediatric emergency department visit: telephone versus e-mail?
AB  - OBJECTIVE: The Internet has become in recent years an unlimited source of health
      related information and revolutionized health information access. Follow-up after
      an emergency department (ED) visit is important for continuity of care but is
      difficult to achieve. We conducted this study to determine whether e-mail could
      become a method for a follow-up contact after leaving the pediatric ED. METHODS:
      Over a 2-month period, parents who had a telephone line and e-mail access and
      whose child was discharged from the ED at the Hospital for Sick Children in
      Toronto were randomized to receive an e-mail or a telephone follow-up. Main
      outcome measure was the response rates by parents to the telephone or e-mail.
      RESULTS: A total of 265 (79%) of the 337 families who were approached had
      Internet access, and the majority (75%) check e-mails at least once a day. Eighty
      seven percent (85 of 98) and 53% (53 of 100) of the families who were contacted
      by telephone or e-mail, respectively, were reached within an average of 17 and 46
      hours, respectively. Fourteen percent of families from the study population were
      unreachable either by telephone or by e-mail. Most (57%) parents who did not
      respond to the e-mail did not check or did not remember reading the e-mail or had
      trouble with access. Ten percent of the e-mails were undeliverable. CONCLUSIONS:
      The telephone is better than e-mail as a follow-up channel with families of
      children who visit the pediatric ED. The main reason for not responding to e
      mails is "technical problems." E-mail could be a mean for follow-up contact for
      part of our patient population, especially for nonurgent purposes.

PMID- 15466096
TI  - Neonatal brain magnetic resonance imaging before discharge is better than serial
      cranial ultrasound in predicting cerebral palsy in very low birth weight preterm
      infants.
AB  - OBJECTIVE: To compare the value of serial cranial ultrasound (US) with a single
      magnetic resonance imaging (MRI) before discharge in very low birth weight
      preterm infants to predict cerebral palsy (CP). METHODS: Infants who weighed
      <1250 g at birth and were <30 weeks' gestational age underwent conventional brain
      MRI at near term (36-40 weeks' postmenstrual age) using 1.5 Tesla MRI scanner.
      Sagittal and axial T1 and T2 fluid attenuated inversion recovery and gradient
      recalled echo images were obtained. Cranial US was also obtained at least twice
      during the first 2 weeks of life. MRI and US images were interpreted by 2
      independent radiologists, who were masked to clinical outcome, and scored as
      follows: category 1, no abnormality; category 2, subependymal hemorrhage or
      mineralization; category 3, moderate to severe ventriculomegaly; category 4,
      focal parenchymal abnormality with or without ventriculomegaly. For the purpose
      of this study, 1 and 2 were categorized as "normal," and 3 and 4 were categorized
      as "abnormal." The infants were assessed at a mean age of 20 and 31 months using
      the Amiel-Tison standardized neurodevelopmental examination. RESULTS: The
      sensitivity and specificity of MRI for predicting CP were 71% and 91% at 20 month
      and 86% and 89% at 31 months, respectively. The sensitivity and specificity of US
      for predicting CP were 29% and 86% at 20 months and 43% and 82% at 31 months.
      CONCLUSIONS: As a predictor of outcome for CP, MRI at near-term in very low birth
      weight preterm neonates is superior to US. However, both US and MRI demonstrate
      high specificity.

PMID- 15466097
TI  - Apparent diffusion coefficient in the posterior limb of the internal capsule
      predicts outcome after perinatal asphyxia.
AB  - OBJECTIVE: Predicting long-term outcome in infants with hypoxic-ischemic
      encephalopathy (HIE) is a difficult task. Magnetic resonance imaging,
      particularly diffusion imaging, holds promise in this regard as it is more
      sensitive to brain injury than any other available imaging modality. Previous
      studies have suggested that abnormal signal intensity in the posterior limb of
      the internal capsule (PLIC), detectable on inversion-recovery T1-weighted
      imaging, is a strong predictor of outcome. The aim of this study was to assess
      the relationship between apparent diffusion coefficient (ADC) values from the
      PLIC, measured by diffusion imaging, and neuromotor outcome in term infants with
      HIE. METHODS: Twenty-eight term infants with a clinical diagnosis of HIE
      underwent magnetic resonance imaging as soon as practicable after birth (mean
      age: 5.6 days), including diffusion-weighted imaging, from which ADC values in
      the PLIC were measured. Motor outcome was assessed in 12 of 16 survivors.
      RESULTS: The ADC value in the PLIC was significantly associated with survival in
      term infants with HIE. For survivors, the mean ADC value in the PLIC was 0.89 +/-
      0.17 microm2/ms, whereas the mean ADC value for nonsurvivors was 0.75 +/- 0.17
      microm2/ms (t = 2.25). Among survivors, the ADC value in the PLIC was also
      associated with neuromotor outcome (F = 5.60). CONCLUSION: The ADC value in the
      PLIC is an indicator of ischemic injury and may be of use as an objective
      prognostic marker for infants with HIE.

PMID- 15466098
TI  - Diffusion-weighted magnetic resonance imaging in term perinatal brain injury: a
      comparison with site of lesion and time from birth.
AB  - OBJECTIVE: The aim of this study was to establish a more objective method for
      confirming tissue injury in term neonates who present with early seizures that
      are believed to be hypoxic-ischemic in origin. METHODS: We studied the
      relationship between contemporaneous diffusion-weighted magnetic resonance
      imaging and conventional magnetic resonance imaging in 63 symptomatic term-born
      neonates and 15 control term infants performed in the neonatal period. Apparent
      diffusion coefficients (ADC) were obtained for multiple regions of the brain.
      RESULTS: ADC values in the 15 control infants were 1 (1-1.15) (median [range]) x
      10(-3)/mm2/second in the thalami and 1.1 (1-1.3) x 10(-3)/mm2/second in the
      lentiform nuclei, 1.5 (1.3-1.7) x 10(-3)/mm2/second in the centrum semiovale, 1.6
      (1.46-1.7) x 10(-3)/mm2/second in the anterior white matter (WM), and 1.55 (1.35
      1.85) x 10(-3)/mm2/second in the posterior WM with little variation over time.
      ADC values were significantly reduced in the first week after severe injury to
      either WM or basal ganglia and thalami (BGT), but values normalized at the end of
      the first week and then increased during week 2. ADC values were either normal or
      increased in moderate BGT and WM lesions when compared with controls. ADC values
      < 1.1 x 10(-3)/mm2/second were always associated with WM infarction and values
      <0.8 x 10(-3)/mm2/second with thalamic infarction. CONCLUSION: A reduced ADC soon
      after delivery allows the presence of tissue infarction to be confirmed at a time
      when conventional imaging changes may be subtle. However, as both moderate WM and
      BGT lesions may have normal or increased ADC values, a normal ADC value during
      the first week does not signify normal tissue. ADC values should always be
      measured in combination with visual analysis of both conventional and diffusion
      weighed images for maximum detection of pathologic tissue, and the timing of the
      scan needs to be taken into account when interpreting the results.

PMID- 15466099
TI  - Cost-effectiveness of postnatal home nursing visits for prevention of hospital
      care for jaundice and dehydration.
AB  - OBJECTIVES: (1) To describe the relationship between postnatal home nursing
      visitation and readmissions and emergency department (ED) visits for neonatal
      jaundice and dehydration in the first 10 days of life. (2) To evaluate the cost
      effectiveness of providing home nursing visits after newborn discharge with
      specific attention to prevention of jaundice and dehydration that require
      hospital-based services. METHODS: A retrospective analysis of a financial
      database allowed for review of the discharge disposition and subsequent care for
      all neonates who were born at a single center from January 2000 through December
      2002. Financial data reflect reimbursement values and costs of care from the
      payers' perspective at the single center. We performed a deterministic cost
      effectiveness analysis using a decision tree that reflected the costs and
      probabilities of infants in each particular health state after nursery discharge.
      RESULTS: A total of 73 (2.8%) of 2641 newborns who did not receive a home visit
      were readmitted to the hospital in the first 10 days of life with jaundice and/or
      dehydration compared with 2 (0.6%) of 326 who did receive a home visit.
      Similarly, 92 (3.5%) of 2641 newborns who were discharged without subsequent home
      nursing care had an ED visit for these reasons in the first 10 days of life
      compared with 0 (0%) of 326 who did have such a visit. Of infants who received a
      home visit, 324 (99.4%) of 326 did not require subsequent hospital services in
      this time period compared with 2497 (94.5%) of 2641 of those who did not receive
      a visit. After nursery discharge, the average cost per child who received a home
      health visit was 109.80 dollars compared with 118.70 dollars for each newborn who
      did not receive a visit. The incremental cost-effectiveness ratio of a routine
      home visit strategy compared with a no visit strategy was -181.82 dollars.
      CONCLUSIONS: A home nursing visit after newborn nursery discharge is highly cost
      effective for reducing the need for subsequent hospital-based services.

PMID- 15466100
TI  - Time in continuity clinic as a predictor of continuity of care for pediatric
      residents.
AB  - OBJECTIVE: In 1996, the Residency Review Committee-Pediatrics recommended
      doubling time in continuity clinic to 2 half days per week. It has yet to be
      demonstrated that increased time in clinic yields greater continuity of care. The
      objective of this study was to determine whether increasing the number of half
      days spent in clinic improves continuity of care for residents. METHODS: We
      reviewed computerized encounter records for all Medical University of South
      Carolina pediatric residents from 1982 to 1998. Depending on the year and the
      resident's training level, house staff spent varying amounts of time in
      continuity clinic. Time in clinic was estimated from grants and materials
      generated in the residency program. We calculated continuity of care from the
      resident's perspective for each individual resident per year using the Continuity
      for Physician (PHY) formula. RESULTS: Continuity for 488 resident-years (200
      residents) was evaluated. Residents spent from 10% to 30% of their time per year
      in clinic. Mean PHY was 57% (interns), 62% (second-year residents), and 52%
      (third-year residents). The correlation coefficient (R) between PHY and
      percentage of time in clinic was .22. In multivariable modeling, percentage of
      time in clinic, training level, and year predicted continuity. An increase of 1
      half day in clinic was associated with an 11% increase in physician continuity.
      When analyses were limited to sick visits, R improved to .58. The effect size
      remained 11%. However, training level and academic year were no longer
      significant. CONCLUSION: Increasing time spent in clinic improves continuity and
      may indeed enhance the quality of this fundamental experience.

PMID- 15466101
TI  - Social smoking among US college students.
AB  - OBJECTIVE: Young smokers commonly identify themselves as "social smokers," a
      pattern of smoking behavior that is poorly understood. We assessed the prevalence
      and correlates of social smoking among US college students. METHODS: Cross
      sectional survey of a random sample of 10,904 students enrolled at 119 nationally
      representative US colleges in 2001. RESULTS: A total of 51% of 2401 current (past
      30-day) smokers were social smokers. (To assess social smoking, students were
      asked, "In the past 30 days, do you smoke mainly when you are with people, mainly
      when you are alone, or do you smoke as often by yourself as with others?"
      Students who stated that they smoked mainly with others rather than alone or
      equally by themselves and others were defined as social smokers for this
      analysis.) Social smoking was independently associated with a lower frequency and
      intensity of tobacco use, less nicotine dependence, less intention to quit, and
      fewer recent quit attempts. CONCLUSIONS: Social smoking is a distinct pattern of
      tobacco use that is common among college students and may represent a stage in
      the uptake of smoking.

PMID- 15466102
TI  - The lingering academic deficits of low birth weight children.
AB  - OBJECTIVE: To estimate the influence of low birth weight (LBW; < or =2500 g) on
      academic achievement in reading and mathematics in 12th grade in 2
      socioeconomically and racially disparate, geographically defined communities.
      METHODS: Representative samples of LBW and normal birth weight (NBW) children who
      were born in 1983-1985 and were from the inner city of Detroit and nearby middle
      class suburbs were assessed longitudinally. Woodcock-Johnson Psycho-Educational
      Battery-Revised standardized tests of reading and mathematics were used at ages
      11 and 17 (n = 773). Multiple regression analysis applying generalized estimating
      equations was used to assess the independent effects of LBW on test scores.
      RESULTS: Compared with NBW children, LBW children manifested deficits of 3 to 5
      points in age-standardized tests of academic achievement at age 17 that had
      persisted with little change from age 11. LBW-related deficits were similar in
      urban and suburban communities and were independent of family factors. At age 17,
      LBW children were approximately 50% more likely than NBW children to score below
      the standardized population mean in both reading and mathematics. The LBW-related
      deficits in academic achievement in adolescence were largely accounted for by LBW
      related deficits in general cognitive abilities, measured by IQ tests at age 6.
      CONCLUSIONS: Interventions to address the lingering effects of LBW on the
      acquisition of core academic skills during the school years should focus on
      preschool LBW children in both inner city and suburban communities.

PMID- 15466103
TI  - Habitual snoring, intermittent hypoxia, and impaired behavior in primary school
      children.
AB  - OBJECTIVES: Sleep-disordered breathing is associated with impaired behavior and
      poor academic performance in children. We aimed to determine the extent of
      behavioral problems in snoring children, clarify the role of intermittent
      hypoxia, and test the reversibility of impaired behavior and poor academic
      performance. METHODS: In 1144 children, habitual snoring (HS; snoring frequently
      or always) and impaired behavior were assessed using parental questionnaires.
      Intermittent hypoxia (ie, presence of > or =5 arterial oxygen desaturations by >
      or =4% or > or =1 desaturation to < or =90%) was investigated with pulse
      oximetry. Poor academic performance (grade 4-6 on a 6-point scale in mathematics,
      science, or spelling) was based on the last school report. HS, impaired behavior,
      and academic performance were reevaluated after 1 year. Adjusted odds ratios
      (ORs) were calculated using unconditional logistic regression. RESULTS: HS was
      significantly associated with hyperactive (OR: 2.4) and inattentive behavior (OR:
      4.0), daytime tiredness (OR: 7.1), and sleepiness (OR: 2.6-4.8). These
      associations were independent of intermittent hypoxia. HS was also significantly
      associated with bad conduct (OR: 2.8), emotional symptoms (OR: 5.5), and peer
      problems (OR: 9.7). At follow-up, hyperactive and inattentive behavior but not
      academic success had significantly improved in children in whom HS had ceased.
      CONCLUSIONS: We suggest that impaired behavior is a key feature of HS independent
      of intermittent hypoxia and improves when HS ceases.

PMID- 15466104
TI  - Limits of the HEDIS criteria in determining asthma severity for children.
AB  - OBJECTIVE: Although the Health Plan Employer Data Information Set (HEDIS) is a
      common method for evaluating the quality of asthma care, its accuracy in
      characterizing persistent asthma in children is unknown. The objective of this
      study was to compare the assessment of asthma severity (persistent vs
      nonpersistent asthma) using the HEDIS criteria versus clinical criteria using
      National Heart, Lung, and Blood Institute (NHLBI) guidelines. METHODS: In a cross
      sectional study, we analyzed baseline data from interviews with the parents of
      896 children who had asthma and participated in a randomized controlled trial.
      Patients had an active clinical diagnosis of asthma, were between 2 and 12 years
      of age, and had no other pulmonary diseases. Patients had persistent asthma by
      parent report according to the HEDIS criteria when, within the last year, they
      had 1 asthma inpatient admission or emergency department visit or 4 asthma
      medication dispensing events, or 4 outpatient asthma visits and at least 2 asthma
      medication dispensing events. Patients had persistent asthma by parent report
      according to the NHLBI criteria when, within the last 2 months, they had
      nighttime asthma symptoms >2 nights/mo or daytime asthma symptoms >2 days/wk. We
      calculated the sensitivity of each HEDIS criterion, separately and then combined,
      using the NHLBI criteria as a gold standard. RESULTS: On the basis of HEDIS
      criteria, 656 (73%) patients had persistent asthma, compared with 338 (38%) using
      NHLBI criteria. Although the HEDIS criteria for persistent asthma were fairly
      sensitive (0.89), they were not very specific (0.70). For children without daily
      controller medications (n = 346), the sensitivity was even lower (0.45), but the
      specificity was similar (0.68). We found that the test characteristics were
      fairly consistent across different age group strata (2-4, 5-9, and 10-12 years of
      age). CONCLUSIONS: HEDIS criteria used to determine the quality of asthma care
      should be interpreted with caution. Although the criteria for persistent disease
      used to determine which children require daily controller medications-are fairly
      sensitive, they are not very specific and include children who may not require
      such medications.

PMID- 15466105
TI  - Counseling parents and children on sun protection: a national survey of
      pediatricians.
AB  - OBJECTIVE: To describe pediatricians' attitudes toward skin cancer (SC), sun
      protection (SP) counseling, and the quantity and content of such counseling and
      to identify barriers to counseling. METHODS: An American Academy of Pediatrics
      Periodic Survey was mailed to 1616 randomly selected US members between October
      2001 and February 2002. The response rate was 54.6%. RESULTS: More than 90% of
      pediatricians agreed that SC is a significant public health problem and that
      preventing episodic high exposures to the sun during childhood will reduce the
      risk of adult melanoma. However, only 22.3% of respondents reported counseling
      most patients in all age groups. Female pediatricians were more likely to counsel
      most patients; pediatricians located in the South and West and those who practice
      in hospital/clinic settings were least likely to counsel compared with those in
      other regions. Approximately half (53%) of pediatricians reported selectively
      counseling on the basis of patient characteristics The most important SP
      recommendation named was using a sunscreen with a sun protection factor > or =15.
      Only 38% of pediatricians rated SP as very important to their patients' health
      compared with other topics such as use of car seats (86%), nutrition (79%),
      immunization issues (76%), and smoking/avoidance of environmental tobacco smoke
      (74%). The most frequently named barrier to SP counseling was lack of time (58%
      reporting). CONCLUSIONS: Although the majority of pediatricians believe that SC
      prevention is a worthy issue, only a minority reported providing routine SP
      counseling to most patients in every age group, and most ranked SP lower in
      importance than other issues. Interventions might include programs and materials
      to educate patients and pediatricians alike. To have an effect on increasing
      rates of SC and SC mortality, a broader public health approach is needed as a
      complement to pediatricians' counseling efforts.

PMID- 15466106
TI  - Measles vaccines and the potential for worldwide eradication of measles.
AB  - The annual number of reported measles cases in the United States has declined
      from between 3 million and 4 million in the prevaccine era to <100 cases in
      association with the highest recorded immunization rates in history. Because of
      continued importation of measles into the United States, young children who are
      not vaccinated appropriately may experience more than a 60-fold increase in risk
      of disease. Unsubstantiated claims suggesting an association between measles
      vaccine and neurologic disorders have led to reduced vaccine use and a resurgence
      of measles in countries where immunization rates have declined below the level
      needed to maintain herd immunity. To address the possibility of worldwide control
      of measles, efforts to ensure high immunization rates among people in both
      developed and developing countries must be sustained.

PMID- 15466107
TI  - Annual variation in respiratory syncytial virus season and decisions regarding
      immunoprophylaxis with palivizumab.

PMID- 15466108
TI  - On continuity of care in pediatric training.

PMID- 15466109
TI  - New guidelines about latent tuberculosis infection in children and adolescents: a
      welcome advancement.

PMID- 15466111
TI  - Supporting vulnerable preschool children: connecting the dots before
      kindergarten.

PMID- 15466110
TI  - Management of hyperbilirubinemia: quality of evidence and cost.

PMID- 15466112
TI  - International Pediatric Congress.

PMID- 15466114
TI  - Severe infantile hypercalcemia associated with Williams syndrome successfully
      treated with intravenously administered pamidronate.
AB  - Infantile hypercalcemia occurs in approximately 15% of children with Williams
      syndrome (WS) and is typically not clinically severe. We report on 3 children
      with WS (confirmed with fluorescent in situ hybridization probes) who presented
      with severe symptomatic hypercalcemia. The first patient's severe hypercalcemia
      resolved with traditional therapies, whereas the subsequent 2 patients were
      treated with intravenously administered pamidronate after traditional measures
      proved only partially successful. Besides asymptomatic mild hypocalcemia, there
      were no complications resulting from pamidronate administration. We conclude that
      WS-associated hypercalcemia can be quite severe and symptomatic and that it can
      be successfully and safely treated with intravenously administered bisphosphonate
      in some cases.

PMID- 15466116
TI  - The pediatrician's role in the prevention of missing children.
AB  - In 2002, the Second National Incidence Studies of Missing, Abducted, Runaway, and
      Thrownaway Children report was released by the US Department of Justice,
      providing new data on a problem that our nation continues to face. This clinical
      report describes the categories of missing children, the prevalence of each, and
      prevention strategies that primary care pediatricians can share with parents to
      increase awareness and education about the safety of their children.

PMID- 15466115
TI  - Lead poisoning from a toy necklace.
AB  - A 4-year-old, previously healthy boy experienced intermittent abdominal pain for
      several weeks. He was diagnosed with probable gastroenteritis, but his symptoms
      worsened. Laboratory tests revealed normocytic anemia, and an abdominal
      radiograph showed a metallic foreign body in the stomach, without evidence of
      obstruction. Endoscopy resulted in the retrieval of a quarter and a medallion
      pendant from the stomach. A venous blood lead level measurement was extremely
      elevated, at 123 microg/dL (level of concern: > or =10 microg/dL). The medallion
      was tested by the state environmental quality laboratory and was found to contain
      38.8% lead (388,000 mg/kg), 3.6% antimony, and 0.5% tin. Similar medallions
      purchased from toy vending machines were analyzed and were found to contain
      similarly high levels of lead. State health officials notified the US Consumer
      Product Safety Commission, which resulted in a national voluntary recall of >1.4
      million metal toy necklaces.

PMID- 15466117
TI  - Providing a primary care medical home for children and youth with cerebral palsy.
AB  - Children and youth with cerebral palsy present pediatricians with complex
      diagnostic and therapeutic challenges. In most instances, care also requires
      communication and comanagement with pediatric subspecialists and pediatric
      surgical specialists, therapists, and community developmental and educational
      teams. The importance of family resilience to the patient's well-being broadens
      the ecologic scope of care, which highlights the value of a primary care medical
      home from which care is initiated, coordinated, and monitored and with which
      families can form a reliable alliance for information, support, and advocacy from
      the time of diagnosis through the transition to adulthood. This report reviews
      the aspects of care specific to cerebral palsy that a medical home should provide
      beyond the routine health maintenance, preventive care, and anticipatory guidance
      needed by all children.

PMID- 15466118
TI  - Guidelines and levels of care for pediatric intensive care units.
AB  - The practice of pediatric critical care medicine has matured dramatically during
      the past decade. These guidelines are presented to update the existing guidelines
      published in 1993. Pediatric critical care services are provided in level I and
      level II units. Within these guidelines, the scope of pediatric critical care
      services is discussed, including organizational and administrative structure,
      hospital facilities and services, personnel, drugs and equipment, quality
      monitoring, and training and continuing education.

PMID- 15466119
TI  - Immunization responses in preterm infants who receive postnatal steroid
      treatment.

PMID- 15466120
TI  - Macrophage activation syndrome mimicking life-threatening infection in a patient
      with variable immunodeficiency, centromeric instability, and facial anomalies.

PMID- 15466123
TI  - Atopic dermatitis and breastfeeding.

PMID- 15466124
TI  - Chickenpox outbreak in a highly vaccinated school population.

PMID- 15466125
TI  - Chickenpox outbreak in a highly vaccinated school population.

PMID- 15466126
TI  - Hemophagocytic lymphohistiocytosis (HLH).

PMID- 15466129
TI  - Flawed attention-deficit/hyperactivity disorder medication comparison.

PMID- 15466131
TI  - Conflict of interest and purpose in bilirubin screening.

PMID- 15466132
TI  - Hyperbilirubinemia guidelines and unintended harms.

PMID- 15466134
TI  - Asthma update: clinical aspects and management.

PMID- 15466135
TI  - Consultation with the specialist: the vulnerable child syndrome.

PMID- 15466136
TI  - Back to basics: acidosis and alkalosis.

PMID- 15466137
TI  - Evidence-based medicine: searching literature and databases for clinical evidence
      (search tools).

PMID- 15466138
TI  - Index of suspicion.

PMID- 15466139
TI  - Subungual hematoma.

PMID- 15466140
TI  - Cerebral cortical aquaporin-4 expression in brain edema following cardiac arrest
      in rats.
AB  - OBJECTIVES: Brain edema occurs following clinical as well as experimental cardiac
      arrest (CA) and predicts a poor neurologic outcome. The objective of this study
      was to determine the expression of cerebral cortex aquaporin (AQP)-4, a member of
      a family of membrane water-channel proteins, in brain edema formation following
      normothermic or hypothermic CA. METHODS: Twenty-four rats were subjected to time
      matched normothermic (N-Sham, 37.5 degrees C +/- 0.5 degrees C, n = 6) or
      hypothermic (H-Sham, 34 degrees C +/- 0.5 degrees C, n = 6) sham experiments and
      normothermic (N-CA, n = 6) or hypothermic (H-CA, n = 6) CA induced by
      asphyxiation for 8 minutes. Hypothermia was induced before CA. The animals were
      resuscitated with cardiopulmonary resuscitation, ventilation, and epinephrine
      administration. Brain edema was determined by brain wet-to-dry weight ratio at
      one hour of resuscitation. AQP4 immunoactivity in the cerebral cortex was
      determined using immunohistochemical staining and was semiquantified as an
      intensity of staining with an automated cell imaging system. RESULTS: Mild
      hypothermia in the sham experiments did not alter cerebral cortex AQP4
      immunoactivity (mean +/- SD) (55.0 +/- 3.7 in H-Sham vs. 53.3 +/- 1.7 in N-Sham,
      p > 0.05). N-CA resulted in a significant increase in AQP4 immunoactivity (61.8
      +/- 4.5) compared with N-Sham (p = 0.01) and H-Sham (p = 0.03). H-CA attenuated
      AQP4 compared with N-CA (53.4 +/- 1.3, p = 0.01). Brain wet-to-dry weight ratios
      were 4.41 +/- 0.07 in N-Sham, 4.40 +/- 0.08 in H-Sham (p > 0.05 vs. N-Sham), 4.55
      +/- 0.04 in N-CA (p = 0.004 vs. N-Sham; p = 0.005 vs. H-Sham), and 4.43 +/- 0.09
      in H-CA (p = 0.02 vs. N-CA; p > 0.05 vs. N-Sham and H-Sham). CONCLUSIONS:
      Cerebral cortical AQP4 expression is up-regulated after normothermic CA, which is
      attenuated by hypothermia induced before CA.

PMID- 15466141
TI  - Rapid Emergency Medicine Score can predict long-term mortality in nonsurgical
      emergency department patients.
AB  - OBJECTIVES: To examine the Rapid Emergency Medicine Score (REMS) as a predictor
      of long-term (4.7 years) mortality in the nonsurgical emergency department (ED).
      METHODS: This was a prospective cohort study. A total of 12,006 nonsurgical
      patients consecutively presenting to an adult ED at a 1,200-bed university
      hospital during a period of one year were enrolled. REMS (including blood
      pressure, respiratory rate, pulse rate, Glasgow Coma Scale score, peripheral
      oxygen saturation, and patient age) was calculated for all patients admitted to
      the ED. The statistical associations between REMS and long-term mortality were
      examined. RESULTS: REMS could predict mortality over 4.7 years (hazard ratio,
      1.26; p < 0.0001). Similar results were obtained in the major patient groups
      (chest pain, stroke, coma, dyspnea, and diabetes). CONCLUSIONS: REMS was a
      powerful predictor of long-term mortality in patients attending the ED for a wide
      range of common nonsurgical disorders.

PMID- 15466142
TI  - Ethanol and illicit drugs do not affect the diagnostic utility of base deficit
      and lactate in differentiating minor from major injury in trauma patients.
AB  - OBJECTIVES: Base deficit (BD) and lactate are valuable screening tools for
      injured patients. They reflect the degree of oxygen debt and have been shown to
      predict outcome. Intake of ethanol and illicit drugs may further derange acid
      base status. The authors evaluated the effect of blood alcohol level (BAL) and
      illicit drugs on admission BD and lactate levels in trauma patients. METHODS:
      Prospective, observational study of trauma patients in a Level 1 trauma center.
      Patients with penetrating or blunt trauma were included in the study. Patients
      were further stratified into major or minor categories. Major was defined by an
      Injury Severity Score >15, blood transfusions, or a decrease in hematocrit of
      more than ten points. Injury categories were further divided into several
      subgroups based on presence or absence of ethanol (BAL > or =0.08 g/dL) or
      positive urine toxicology screen (Utox). RESULTS: A total of 520 patients (84%
      male) with a mean (+/-SD) age of 33 (+/-15) years were studied. Compared with the
      minor injury categories, BD and lactate levels were significantly higher in the
      major injury categories in all different intoxication subgroups. Testing the
      diagnostic performance of BD and lactate in detecting major injury, the authors
      observed significant (p < 0.05) differences between the areas under the receiver
      operating characteristic curves for these two diagnostic tests compared with
      baseline in both intoxicated (BAL > or =0.08 g/dL and/or positive Utox) and
      nonintoxicated (BAL <0.08 g/dL and negative Utox) patients. CONCLUSIONS: The
      presence of ethanol and/or illicit drugs did not affect the ability of BD or
      lactate to identify patients with major injuries.

PMID- 15466143
TI  - Clinical value of the total white blood cell count and temperature in the
      evaluation of patients with suspected appendicitis.
AB  - OBJECTIVES: The total white blood cell (WBC) count and temperature are often
      expected to be elevated in patients with appendicitis. Clinicians often use the
      results of these parameters in making a judgment about the presence or absence of
      disease. The objective of this study was to assess the discriminatory value of
      the total WBC count and presenting body temperature in patients presenting to the
      emergency department (ED) with signs and symptoms suggestive of appendicitis.
      METHODS: This was a prospective consecutive case series in a university ED with
      an annual census of 38,000. All patients presenting to the ED in whom the
      diagnosis of appendicitis was the attending physician's primary consideration
      were enrolled. Measures included age, gender, symptoms, physical findings,
      patient temperature as taken in the ED, initial total WBC count, and discharge
      diagnosis. Admitted patients were followed up until surgical or clinical
      outcomes, and discharged patients were followed up by telephone two weeks after
      the initial visit. All statistical analysis was performed using StatsDirect
      version 1.9.8. RESULTS: A total of 293 patients were enrolled over a two-year
      study period. The total WBC count was measured in 274 cases, and the temperature
      was measured in 293 cases. There were 130 male patients and 163 female patients.
      The mean age of the patients was 30.8 years (range, 7-75 years). Appendicitis was
      confirmed in 92 patients. In this study group of patients, a total WBC count
      >10,000 cells/mm(3) had a sensitivity of 76% (95% confidence interval [95% CI] =
      65% to 84%) and a specificity of 52% (95% CI = 45% to 60%). The positive
      predictive value (PPV) was 42% (95% CI = 35% to 51%), and the negative predictive
      value (NPV) was 82% (95% CI = 74% to 89%). The positive likelihood ratio (LR) was
      1.59 (95% CI = 1.31 to 1.93), and the negative LR was 0.46 (95% CI = 0.31 to
      0.67). A temperature >99.0 degrees F had a sensitivity of 47% (95% CI = 36% to
      57%) and a specificity of 64% (95% CI = 57% to 71%). The PPV was 37% (95% CI =
      29% to 46%), and the NPV was 72% (95% CI = 65% to 79%). The positive LR was 1.3
      (95% CI = 0.97 to 1.72), and the negative LR was 0.82 (95% CI = 0.65 to 1.01).
      The areas under the curve for the receiver-operating characteristic (ROC) curve
      were 0.72 (95% CI = 0.65 to 0.79) and 0.59 (95% CI = 0.52 to 0.66) for an
      elevated total WBC count and an elevated temperature, respectively. CONCLUSIONS:
      An elevated total WBC count >10,000 cells/mm(3), while statistically associated
      with the presence of appendicitis, had very poor sensitivity and specificity and
      almost no clinical utility. There was minimal statistical association between a
      temperature of >99 degrees F and the presence of appendicitis. The ROC curve
      suggests there is no value of total WBC count or temperature that has sufficient
      sensitivity and specificity to be of clinical value in the diagnosis of
      appendicitis. Clinicians should be wary of reliance on either elevated
      temperature or total WBC count as an indicator of the presence of appendicitis.

PMID- 15466144
TI  - Characteristics and admission patterns of patients presenting with syncope to
      U.S. emergency departments, 1992-2000.
AB  - OBJECTIVES: To describe the characteristics and admission patterns of patients
      with syncope presenting to U.S. emergency departments (EDs). METHODS: The ED
      portion of the National Hospital Ambulatory Medical Care Survey, 1992-2000, was
      analyzed. Nationally representative weighted estimates for incidence and
      admission rates were estimated and stratified by demographic variables. Presence
      of cardiovascular diagnoses on ED discharge was noted. RESULTS: Of the 865
      million ED visits during the nine-year study period, an estimated 6.7 million
      (0.77%; 95% confidence interval [95% CI] = 0.69% to 0.85%) were related to
      syncope. Higher incidences of ED visits for syncope were found in elder, female,
      and non-Hispanic patients compared with their reference groups. The overall
      admission rate was 32% (95% CI = 28% to 36%). Older, male, and white patients
      were admitted more frequently than their counterparts. Of patients older than 80
      years of age, 58% (95% CI = 49% to 67%) were admitted. Associated cardiovascular
      International Classification of Diseases, Ninth Revision (ICD-9), codes for
      ischemic, structural, and arrhythmic heart disease were noted in 10% (95% CI = 8%
      to 13%) of patients, and 66% (95% CI = 56% to 76%) of these patients were
      admitted. CONCLUSIONS: Syncope is a frequent reason for ED visits and admissions.
      Elders and patients with associated cardiovascular diagnoses are frequently
      discharged, and admission practices appear to deviate from consensus panel
      guidelines.

PMID- 15466145
TI  - Cause-and-effect analysis of risk management files to assess patient care in the
      emergency department.
AB  - OBJECTIVES: Identifying the etiologies of adverse outcomes is an important first
      step in improving patient safety and reducing malpractice risks. However,
      relatively little is known about the causes of emergency department-related
      adverse outcomes. The objective was to describe a method for identification of
      common causes of adverse outcomes in an emergency department. This methodology
      potentially can suggest ways to improve care and might provide a model for
      identification of factors associated with adverse outcomes. METHODS: This was a
      retrospective analysis of 74 consecutive files opened by a malpractice insurer
      between 1995 and 2000. Each risk-management file was analyzed to identify
      potential causes of adverse outcomes. The main outcomes were rater-assigned codes
      for alleged problems with care (e.g., failures of communication or problems
      related to diagnosis). RESULTS: About 50% of cases were related to injuries or
      abdominal complaints. A contributing cause was found in 92% of cases, and most
      had more than one contributing cause. The most frequent contributing categories
      included failure to diagnose (45%), supervision problems (31%), communication
      problems (30%), patient behavior (24%), administrative problems (20%), and
      documentation (20%). Specific relating factors within these categories, such as
      lack of timely resident supervision and failure to follow policies and
      procedures, were identified. CONCLUSIONS: This project documented that an
      aggregate analysis of risk-management files has the potential to identify shared
      causes related to real or perceived adverse outcomes. Several potentially
      correctable systems problems were identified using this methodology. These
      simple, descriptive management tools may be useful in identifying issues for
      problem solving and can be easily learned by physicians and managers.

PMID- 15466146
TI  - External causes of pediatric injury-related emergency department visits in the
      United States.
AB  - OBJECTIVES: To characterize the types and external causes of pediatric injury
      related visits (IRVs) to emergency departments (EDs), in particular, sports
      related injuries. To compare the characteristics of children with IRVs with those
      with non-IRVs, specifically, differences in IRV rates by race and ethnicity and
      by health insurance. METHODS: This was a stratified random-sample survey of EDs
      in the National Hospital Ambulatory Medical Care Survey (NHAMCS), including all
      IRVs for patients less than 19 years of age in 1998 (n = 2,656). National
      estimates of pediatric IRVs were obtained using the assigned patient visit
      weights in the NHAMCS databases and SUDAAN analyses. Measures of association
      between predictor variables (patient and health insurance characteristics) and
      whether a child had an IRV were calculated using multivariate logistic regression
      analyses to determine adjusted odds ratios with 95% confidence intervals.
      RESULTS: Pediatric IRVs accounted for more than 11 million ED visits annually.
      The most common diagnoses for IRVs were open wounds, contusions, sprains and
      strains, and fractures and dislocations. The leading external causes of IRVs were
      sports-related injuries, accidental falls, being struck by objects, and motor
      vehicle collisions. Children with IRVs differed from those who presented for non
      IRVs in many characteristics: they were more likely to be male, to be older, to
      be of white race, and to have private insurance, and less likely to be of Asian
      or Hispanic ethnicity. CONCLUSIONS: Sports and recreation are the leading
      external causes of pediatric IRVs to EDs in the United States. There are
      different patterns of IRVs according to gender, age, race, ethnicity, and
      insurance. Identification of specific patterns of injury is necessary for the
      design of effective prevention strategies.

PMID- 15466147
TI  - The association between white blood cell count and acute myocardial infarction in
      hospital mortality: findings from the National Registry of Myocardial Infarction.
AB  - OBJECTIVES: Although cross-sectional and prospective studies have shown that the
      white blood cell (WBC) count is associated with long-term mortality for patients
      with ischemic heart disease, the role of the WBC count as an independent
      predictor of short-term mortality in patients with acute myocardial infarction
      (AMI) has not been examined as extensively. The objective of this study was to
      determine whether the WBC count is associated with in-hospital mortality for
      patients with ischemic heart disease after controlling for potential confounders.
      METHODS: From July 31, 2000, to July 31, 2001, the National Registry of
      Myocardial Infarction 4 enrolled 186,727 AMI patients. A total of 115,273
      patients were included in the analysis. RESULTS: WBC counts were subdivided into
      intervals of 1,000/mL, and in-hospital mortality rates were determined for each
      interval. The distribution revealed a J-shaped curve. Patients with WBC counts
      >5,000/mL were subdivided into quartiles, whereas patients with WBC counts
      <5,000/mL were assigned to a separate category labeled "subquartile" and were
      analyzed separately. A linear increase in in-hospital mortality by WBC count
      quartile was found. The unadjusted odds ratio (OR) for the fourth versus the
      first quartile showed strong associations with in-hospital mortality among the
      entire population and by gender: 4.09 (95% confidence interval [95% CI] = 3.83 to
      4.73) for all patients, 4.31 (95% CI = 3.93 to 4.73) for men, and 3.65 (95% CI =
      3.32 to 4.01) for women. Following adjustment for covariates, the magnitude of
      the ORs attenuated, but the ORs remained highly significant (OR, 2.71 [95% CI =
      2.53 to 2.90] for all patients; OR, 2.87 [95% CI = 2.59 to 3.19] for men; OR,
      2.61 [95% CI = 2.36 to 2.99] for women). Reperfused patients had consistently
      lower in-hospital mortality rates for all patients and by gender (p < 0.0001).
      CONCLUSIONS: The WBC count is an independent predictor of in-hospital AMI
      mortality and may be useful in assessing the prognosis of AMI in conjunction with
      other early risk-stratification factors. Whether elevated WBC count is a marker
      of the inflammatory process or is a direct risk factor for AMI remains unclear.
      Given the simplicity and availability of the WBC count, the authors conclude that
      the WBC count should be used in conjunction with other ancillary tests to assess
      the prognosis of a patient with AMI.

PMID- 15466148
TI  - Tracers in emergency medical services research.

PMID- 15466149
TI  - The illusion of explanation.

PMID- 15466150
TI  - Establishing the scope and methodological approach to out-of-hospital outcomes
      and effectiveness research.
AB  - Outcomes research offers out-of-hospital medicine a valuable methodology for
      studying the effectiveness of services provided in the out-of hospital setting. A
      clear understanding of the history and constructs of outcomes research is
      necessary for its integration into emergency medical services research. This
      report describes the conceptual framework of outcomes research and key
      methodological considerations for the successful implementation of out-of
      hospital outcomes research. Illustrations of the specific applications of
      outcomes research and implications to existing methodologies are given, as well
      as suggestions for improved interdisciplinary research.

PMID- 15466151
TI  - Risk adjustment and outcome measures for out-of-hospital respiratory distress.
AB  - The purpose of the Emergency Medical Services Outcomes Project (EMSOP) is to
      develop a foundation and framework for out-of-hospital outcomes research. In
      prior work, this group delineated the priority conditions, described conceptual
      models, suggested core and risk adjustment measures potentially useful to
      emergency medical services research, and summarized out-of-hospital pain
      measurement. In this fifth article in the EMSOP series, the authors recommend
      specific risk-adjustment measures and outcome measures for use in out-of-hospital
      research on patients presenting with respiratory distress. The methodology
      included systematic literature searches and a structured review by an expert
      panel. The EMSOP group recommends use of pulse oximetry, peak expiratory flow
      rate, and the visual analog dyspnea scale as potential risk-adjustment measures
      and outcome measures for out-of-hospital research in patients with respiratory
      distress. Furthermore, using mortality as an outcome measure is also recommended.
      Future research is needed to alleviate the paucity of validated tools for out-of
      hospital outcomes research.

PMID- 15466152
TI  - Confronting the ethical challenges to informed consent in emergency medicine
      research.
AB  - The Society for Academic Emergency Medicine believes that protection of human
      subjects is vital in emergency medicine research and that, whenever feasible,
      informed consent is at the heart of that protection. At the same time, the
      emergency setting presents unique barriers to informed consent both because of
      the time frame in which the research is performed and because patients in the
      emergency department are a vulnerable population. This report reviews the concept
      of informed consent, empirical data on patients' cognitive abilities during an
      emergency, the federal rules allowing exemption from consent under certain
      circumstances, issues surrounding consent forms, and the new Health Insurance
      Portability and Accountability Act regulations as they relate to research. The
      authors conclude that, in many circumstances, informed consent is possible if the
      researcher is diligent and takes time to adequately explain the study to the
      potential subject. In cases in which it is possible to obtain consent,
      precautions must be taken to ensure that subjects have decision-making capacity
      and are offered time to have their questions answered and their needs met.
      Sometimes resuscitation and other emergency medicine research must be conducted
      without the ability to obtain consent. In these cases, special protections of
      subjects under the exception from consent guidelines must be followed. Protection
      of research subjects is the responsibility of every researcher in emergency
      medicine.

PMID- 15466153
TI  - The Society for Academic Emergency Medicine position on informed consent for
      emergency medicine research.

PMID- 15466154
TI  - Executive summary: The Emergency Neurologic Clinical Trials Network meeting--a
      National Institute of Neurological Disorders and Stroke symposium.

PMID- 15466155
TI  - Care in the emergency department: how crowded is overcrowded?
AB  - OBJECTIVES: To examine how emergency department (ED) overcrowding has been
      defined in the medical literature. METHODS: Using the National Library of
      Medicine's PubMed and MEDLINE databases (1966 to 2002), a comprehensive review of
      the English-language medical literature was conducted to identify explicit
      criteria for defining ED overcrowding. Inclusion criteria were original articles,
      editorials, and reviews; news articles and letters to the editor were excluded.
      Using a standardized extraction form, publications were described as primary if
      the title or an objective statement in the introductory or methods paragraph
      referred to crowding or overcrowding; all other citations were categorized as
      secondary. Each report was then evaluated to determine whether crowding or
      overcrowding was defined explicitly or implicitly. Explicit definitions included
      phrases such as "Crowding was defined as ..." or "Overcrowding occurred when
      ..."; other definitions were characterized as implicit. RESULTS: A total of 231
      candidate articles were identified; 91 met inclusion criteria, and 53 (58%) were
      primary articles about ED crowding or overcrowding. Among these primary articles,
      23 (43%) had explicit definitions of crowding or overcrowding. The definitions
      varied widely in content and focus, including ED, hospital, or external
      (nonhospital) factors. CONCLUSIONS: Although ED overcrowding has been a topic of
      frequent investigation, current definitions of the problem are often implicit or
      focus on factors outside of the ED itself. A more consistent approach to defining
      ED overcrowding would help to clarify the distinctions between causes,
      characteristics, and outcomes of overcrowding.

PMID- 15466156
TI  - A multicasualty event: out-of-hospital and in-hospital organizational aspects.
AB  - In a wedding celebration of 700 participants, the third floor of the hall in
      which the celebration was taking place suddenly collapsed. While the walls
      remained intact, all three floors of the building collapsed, causing Israel's
      largest disaster. OBJECTIVES: To study the management of a multicasualty event
      (MCE), in the out-of-hospital and in-hospital phases, including rescue, emergency
      medical services (EMS) deployment and evacuation of casualties, emergency
      department (ED) deployment, recalling staff, medical care, imaging procedures,
      hospitalization, secondary referral, and interhospital transfer of patients.
      METHODS: Data on all the victims who arrived at the four EDs in Jerusalem were
      collected through medical files, telephone interviews, and hospital computerized
      information. RESULTS: The disaster resulted in 23 fatalities and 315 injured
      people; 43% were hospitalized. During the first hour, 42% were evacuated and
      after seven hours the scene was empty. Ninety-seven basic life support
      ambulances, 18 mobile intensive care units, 600 emergency medical technicians, 40
      paramedics, and 15 physicians took part in the out-of-hospital stage. At the
      hospitals, about 1,300 staff members arrived immediately, either on demand or
      voluntarily, a number that seems too large for this disaster. Computed tomography
      (CT) demand was over its capability. CONCLUSIONS: During this MCE, the authors
      observed "rotating" bottleneck phenomena within out-of-hospital and in-hospital
      systems. For maximal efficiency, hospitals need to fully coordinate the influx
      and transfer of patients with out-of-hospital rescue services as well as with
      other hospitals. Each hospital has to immediately deploy its operational center,
      which will manage and monitor the hospital's resources and facilitate
      coordination with the relevant institutions.

PMID- 15466157
TI  - An evaluation of a blind rotational technique for selective mainstem intubation.
AB  - OBJECTIVES: Although rare, massive hemoptysis and major bronchial disruptions are
      associated with high mortality. Selective ventilation of the uninvolved lung can
      increase the likelihood of survival. Specialized devices used for single lung
      ventilation are often not readily available and can be difficult to place in the
      emergency department. The authors evaluated a blind rotational technique for
      selective mainstem intubation using either a standard endotracheal tube (ET) or a
      directional-tip endotracheal tube (DTET). METHODS: This was a prospective,
      randomized trial on 25 human cadavers. The desired side of mainstem intubation
      was determined by randomization. Each cadaver was used for four ET, four DTET,
      and four control intubations. In the ET group, the trachea was intubated. The
      tube was then rotated 90 degrees in the direction of the desired placement and
      advanced until resistance was met. In the DTET group, the technique was
      identical, except the trigger was activated to flex the tip during advancement.
      In the control group, an ET was advanced in neutral alignment until resistance
      was met. A bronchoscopist blinded to the desired placement determined tube
      position. Comparison testing was performed using Pearson's chi-square test.
      RESULTS: When attempting to intubate the left mainstem, use of the ET with the
      rotational technique was successful 72.3% of the time (95% confidence interval
      [95% CI] = 57% to 84%). Intubation of the left mainstem using the DTET was
      successful 68.5% of the time (95% CI = 54% to 81%; p = 0.67). Attempts to
      selectively intubate the right mainstem using the rotational technique were
      highly successful in both groups: 94% for the ET (95% CI = 84% to 99%) versus
      97.8% for the DTET (95% CI = 89% to 100%). Among controls, the right mainstem was
      intubated 93% of the time (95% CI = 86% to 97%). CONCLUSIONS: In a cadaveric
      model, the left mainstem bronchus can be selectively intubated with moderate
      reliability using this rotational technique. Use of a DTET confers no significant
      advantage. The ability to generalize these findings to living subjects is
      unknown.

PMID- 15466158
TI  - A dynamic transcriptional network communicates growth potential to ribosome
      synthesis and critical cell size.
AB  - Cell-size homeostasis entails a fundamental balance between growth and division.
      The budding yeast Saccharomyces cerevisiae establishes this balance by enforcing
      growth to a critical cell size prior to cell cycle commitment (Start) in late G1
      phase. Nutrients modulate the critical size threshold, such that cells are large
      in rich medium and small in poor medium. Here, we show that two potent negative
      regulators of Start, Sfp1 and Sch9, are activators of the ribosomal protein (RP)
      and ribosome biogenesis (Ribi) regulons, the transcriptional programs that
      dictate ribosome synthesis rate in accord with environmental and intracellular
      conditions. Sfp1 and Sch9 are required for carbon-source modulation of cell size
      and are regulated at the level of nuclear localization and abundance,
      respectively. Sfp1 nuclear concentration responds rapidly to nutrient and stress
      conditions and is regulated by the Ras/PKA and TOR signaling pathways. In turn,
      Sfp1 influences the nuclear localization of Fhl1 and Ifh1, which bind to RP gene
      promoters. Starvation or the absence of Sfp1 causes Fhl1 and Ifh1 to localize to
      nucleolar regions, concomitant with reduced RP gene transcription. These findings
      suggest that nutrient signals set the critical cell-size threshold via Sfp1 and
      Sch9-mediated control of ribosome biosynthetic rates.

PMID- 15466159
TI  - Dosage-sensitive requirement for mouse Dll4 in artery development.
AB  - Involvement of the Notch signaling pathway in vascular development has been
      demonstrated by both gain- and loss-of-function mutations in humans, mice, and
      zebrafish. In zebrafish, Notch signaling is required for arterial identity by
      suppressing the venous fate in developing artery cells. In mice, the Notch4
      receptor and the Delta-like 4 (Dll4) ligand are specifically expressed in
      arterial endothelial cells, suggesting a similar role. Here we show that the Dll4
      ligand alone is required in a dosage-sensitive manner for normal arterial
      patterning in development. This implicates Dll4 as the specific mammalian
      endothelial ligand for autocrine endothelial Notch signaling, and suggests that
      Dll4 may be a suitable target for intervention in arterial angiogenesis.

PMID- 15466160
TI  - Haploinsufficient lethality and formation of arteriovenous malformations in Notch
      pathway mutants.
AB  - The Notch signaling pathway is essential for embryonic vascular development in
      vertebrates. Here we show that mouse embryos heterozygous for a targeted mutation
      in the gene encoding the DLL4 ligand exhibit haploinsufficient lethality because
      of defects in vascular remodeling. We also describe vascular defects in embryos
      homozygous for a mutation in the Rbpsuh gene, which encodes the primary
      transcriptional mediator of Notch signaling. Conditional inactivation of Rpbsuh
      function demonstrates that Notch activation is essential in the endothelial cell
      lineage. Notch pathway mutant embryos exhibit defects in arterial specification
      of nascent blood vessels and develop arteriovenous malformations. These results
      demonstrate that vascular remodeling in the mouse embryo is sensitive to Dll4
      gene dosage and that Notch activation in endothelial cells is essential for
      embryonic vascular remodeling.

PMID- 15466161
TI  - Tsc2 is not a critical target of Akt during normal Drosophila development.
AB  - Signaling by insulin and target of rapamycin are both required for cell growth,
      but their interrelationships remain poorly defined. It was reported that Akt, an
      essential component of the insulin pathway, stimulates growth by phosphorylating
      and inhibiting tuberous sclerosis complex 2 (TSC2). Here we evaluate this model
      genetically in Drosophila by engineering Tsc2 mutants in which the Akt
      phosphorylation sites are changed to nonphosphorylatable or phospho-mimicking
      residues. Strikingly, such mutants completely rescue the lethality and cell
      growth defects of Tsc2-null mutants. Taken together, our data suggest that Tsc2
      is not a critical substrate of Akt in normal Drosophila development.

PMID- 15466162
TI  - Lack of evidence for induction of CYP2B1, CYP3A23, and CYP1A2 gene expression by
      Panax ginseng and Panax quinquefolius extracts in adult rats and primary cultures
      of rat hepatocytes.
AB  - Treatment of rats with a single oral dose (10-30 mg/kg) of a crude Panax ginseng
      extract of unknown ginsenoside content has been reported to modestly increase
      hepatic microsomal cytochrome P450-mediated aminopyrine N-demethylation activity.
      In the present study, we compared the effect of P. ginseng and Panax
      quinquefolius extracts on rat hepatic CYP2B1, CYP3A23, and CYP1A2 gene
      expression. Adult male Sprague-Dawley rats (250-275 g) received, by oral gavage
      or i.p., P. ginseng extract [4% (w/w) total ginsenosides; 30 or 100 mg/kg/day for
      1 or 4 days], P. quinquefolius extract [10% (w/w) total ginsenosides; 100 or 400
      mg/kg/day for 21 consecutive days), or an equivalent volume (2 ml/kg) of the
      vehicle (0.9% NaCl or 0.3% carboxymethylcellulose) and were terminated 1 day
      after the last dose. P. ginseng and P. quinquefolius extracts did not affect body
      weight gain, absolute or relative liver weight, hepatic CYP2B1, CYP3A23, or
      CYP1A2 mRNA expression, or microsomal CYP2B-mediated 7-benzyloxyresorufin O
      dealkylation (BROD) or CYP1A-mediated 7-ethoxyresorufin O-dealkylation (EROD)
      activity. In contrast, results from positive control experiments indicated that
      phenobarbital increased CYP2B1 mRNA and BROD activity, dexamethasone increased
      CYP3A23 mRNA, and beta-naphthoflavone increased CYP1A2 mRNA and EROD activity
      levels. Treatment of primary cultures of rat hepatocytes with either of the
      ginseng extracts (0.1-1000 microg/ml for 2 days) also did not affect CYP2B1 or
      CYP3A23 mRNA expression. Overall, our data indicate that P. ginseng and P.
      quinquefolius extracts do not increase rat hepatic CYP2B1, CYP3A23, or CYP1A2
      gene expression.

PMID- 15466163
TI  - High volume bioassays to assess CYP3A4-mediated drug interactions: induction and
      inhibition in a single cell line.
AB  - Exposure to certain xenochemicals can alter the catalytic activity of the major
      drug-metabolizing enzyme, CYP3A4, either by enhancing expression of this
      cytochrome P450 or inhibiting its activity. Such alterations can result in
      adverse consequences stemming from drug-drug interactions. A simplified and
      reliable tool for detecting the ability of candidate drugs to alter CYP3A4 levels
      or inhibit catalytic activity was developed by stable integration of human
      pregnane X receptor and a luciferase vector harboring the CYP3A4 enhancers.
      Treatment of stable transformants, namely DPX-2, with various concentrations of
      inducers including rifampicin, mifepristone, troglitazone, methoxychlor, and kava
      produced dose-dependent increases in luciferase expression (between 2- and 40
      fold above dimethyl sulfoxide-treated cells). Northern blot analyses of CYP3A4
      mRNA in DPX-2 cells exhibited a good correlation to results generated with the
      reporter gene assay (r(2) = 0.5, p < 0.01). Induction of CYP3A4 protein was
      examined by measuring catalytic activity with the CYP3A4 substrate, luciferin 6'
      benzyl ether (luciferin BE). Metabolism of luciferin BE by DPX-2 cells was
      enhanced 5.2-fold above dimethyl sulfoxide-treated cells by treatment with
      rifampicin. Constitutive androstane receptor-mediated regulation of CYP3A4
      protein was addressed by measuring catalytic activity in a separate cell line
      over-expressing this receptor. Phenobarbital and dexamethasone produced 1.5- and
      2.0-fold increases, respectively, above control in luciferin BE metabolism. To
      determine the utility of DPX-2 cells for identifying inhibitors of CYP3A4
      catabolism, luciferin BE activity was measured in the presence of various
      concentrations of ketoconazole, erythromycin, or kava. These agents exhibited
      dose-dependent decreases in CYP3A4 activity with IC(50) values of 0.3 microM for
      ketoconazole, 108 microM for erythromycin, and 15.5 microg/ml for kava.
      Collectively, DPX-2 cells were used to identify xenobiotics that induce or
      inhibit CYP3A4 in a high throughput manner, demonstrating their applicability to
      early-stage drug development.

PMID- 15466164
TI  - The roles of transporters and enzymes in hepatic drug processing.
AB  - A simple, physiological model was used to illustrate the competing nature of
      transporters and metabolic enzymes in hepatic drug processing. Enalapril, a drug
      whose basolateral influx and canalicular efflux are mediated by rat organic anion
      transporting polypeptide 1 (Oatp1) and rat multidrug resistance-associated
      protein 2 (Mrp2), respectively, and metabolism by the carboxylesterases, was
      enlisted as the example to illustrate how the transport and intrinsic clearances
      are inter-related in the estimation of the hepatic and metabolic, and excretion
      clearances. Moreover, simulations were performed to explore the effects of
      inhibitors or inducers of transporters/enzymes to unravel the compensatory
      changes of alternate pathways. Generally speaking, inhibition of one pathway led
      to an apparent increase in the alternate (competing) pathway and total hepatic
      clearance was decreased; induction would lead to an apparent decrease in the
      alternate pathway and an increase in total hepatic clearance. A reduction in
      influx clearance brought about parallel decreases in the biliary and metabolic
      clearances, whereas a reduction in efflux basolateral clearance evoked similar
      increases in biliary and metabolic clearances. However, the steady-state tissue
      concentration (C(L,ss)) or area under the tissue concentration-time curve
      (AUC(L)) was reliant only on the unbound fraction in liver, and the secretory and
      metabolic intrinsic clearances and not the influx and efflux clearances.
      Variations in the influx and efflux intrinsic clearances evoked temporal changes
      in the tissue concentration-time profile but not the AUC(L) or C(L,ss). The
      pharmacokinetic theory developed offers data interpretation from literature
      reports on P-glycoprotein and cytochrome P450 substrates with mdr1a/1b knockout
      versus wild-type mice, and rat liver perfusion studies, with and without the use
      of inhibitors. In some cases, critiques on data interpretation were made.

PMID- 15466165
TI  - Molecular characterization of a third case of human atransferrinemia.

PMID- 15466166
TI  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency-type Zurich: a splice site
      mutation as an uncommon mechanism producing enzyme deficiency.

PMID- 15466167
TI  - Roles of cGMP/cGMP-dependent protein kinase in platelet activation.

PMID- 15466168
TI  - H2-Ea deficiency is a risk factor for bleomycin-induced lung fibrosis in mice.
AB  - Pulmonary fibrosis is a significant complication in cancer patients when treated
      by radiation, e.g., thoracic malignant diseases, or chemotherapeutic agents.
      Bleomycin is one of the primary drugs used to treat testicular cancer, but the
      incidence of significant pulmonary fibrosis limits the dose. It is known that
      susceptibility to bleomycin-induced pulmonary fibrosis is a heritable trait
      controlled by multiple genes, none of which, however, are yet known. In this
      study, we used expression profiling and genetic analysis in mouse models of
      bleomycin-induced pulmonary fibrosis and identified MHC class II antigen Ealpha
      (H2-Ea) as a risk factor for this disease. We found that a loss-of-function
      deletion in the H2-Ea gene was linked to susceptibility. A functional test of H2
      Ea in transgenic mice showed 100% survival in the transgenic mice compared with
      53% in C57BL/10J mice and significantly decreased pulmonary fibrosis from 16.42%
      (C57BL/10J) to 5.76% (transgenic; P = 1.20e(-8)). These results show that H2-Ea
      expression protects mice from bleomycin-induced pulmonary fibrosis, which
      implicates H2-Ea as a candidate susceptibility gene for pulmonary fibrosis.

PMID- 15466169
TI  - A recurrent chromosome breakpoint in breast cancer at the NRG1/neuregulin
      1/heregulin gene.
AB  - Most studies of genomic rearrangements in common cancers have focused on regional
      gains and losses, but some rearrangements may break within specific genes. We
      previously reported that five breast cancer cell lines have chromosome
      translocations that break in the NRG1 gene and that could cause abnormal NRG1
      expression. NRG1 encodes the Neuregulins 1 (formerly the Heregulins), ligands for
      members of the ErbB/epidermal growth factor-receptor family, which includes
      ErbB2/HER2. We have now screened for breaks at NRG1 in paraffin sections of
      breast tumors. Tissue microarrays were screened by fluorescence in situ
      hybridization, with hybridization probes proximal and distal to the expected
      breakpoints. This screen detects breaks but does not distinguish between
      translocation or deletion breakpoints. The screen was validated with array
      comparative genomic hybridization on a custom 8p12 high-density genomic array to
      detect a lower copy number of the sequences that were lost distal to the breaks.
      We also precisely mapped the breaks in five tumors with different hybridization
      probes. Breaks in NRG1 were detected in 6% (19 of 323) of breast cancers and in
      some lung and ovarian cancers. In an unselected series of 213 cases with follow
      up, breast cancers where the break was detected tended to be high-grade (65%
      grade III compared with 28% of negative cases). They were, like breast tumors in
      general, mainly ErbB2 low (11 of 13 were low) and estrogen receptor positive (11
      of 13 positive).

PMID- 15466170
TI  - Schedule-dependent inhibition of hypoxia-inducible factor-1alpha protein
      accumulation, angiogenesis, and tumor growth by topotecan in U251-HRE
      glioblastoma xenografts.
AB  - We have previously shown that topotecan, a topoisomerase I poison, inhibits
      hypoxia-inducible factor (HIF)-1alpha protein accumulation by a DNA damage
      independent mechanism. Here, we report that daily administration of topotecan
      inhibits HIF-1alpha protein expression in U251-HRE glioblastoma xenografts.
      Concomitant with HIF-1alpha inhibition, topotecan caused a significant tumor
      growth inhibition associated with a marked decrease of angiogenesis and
      expression of HIF-1 target genes in tumor tissue. These results provide a
      compelling rationale for testing topotecan in clinical trials to target HIF-1 in
      cancer patients.

PMID- 15466171
TI  - Nitric oxide, a mediator of inflammation, suppresses tumorigenesis.
AB  - Inflammation influences the development of cancer. The nitric oxide synthase
      (NOS2) is induced by inflammatory cytokines, e.g., tumor necrosis factor alpha
      and interleukin 1beta, and produces nitric oxide (NO*), a critical mediator of
      the inflammatory response. Because p53 governs NO* production by
      transcriptionally transrepressing NOS2, we used a genetic strategy to determine
      whether NO* and p53 cooperatively regulate tumorigenesis. Lymphomas developed
      more rapidly in p53-/-NOS2-/- or p53-/-NOS2+/- mice than in p53-/-NOS2+/+ mice
      that were cross-bred into a >95% C57BL6 background and maintained in a pathogen
      free condition. Likewise, sarcomas and lymphomas developed faster in p53+/-NOS2-/
      or p53+/-NOS2+/- than in p53+/-NOS2+/+ mice. When compared with the double
      knockout mice, p53-/-NOS2+/+ mice showed a higher apoptotic index and a decreased
      proliferation index with an increased expression of death receptor ligands, CD95
      L and tumor necrosis factor-related apoptosis-inducing ligand, and the cell cycle
      checkpoint protein, p21(waf1), in the spleen and thymus before tumor development.
      Furthermore, mice deficient in both p53 and NOS2 produced a high level of anti
      inflammatory interleukin 10 when compared with p53-deficient mice. These studies
      provide genetic and mechanistic evidence that NO* can suppress tumorigenesis.

PMID- 15466172
TI  - JAGGED1 expression is associated with prostate cancer metastasis and recurrence.
AB  - Recent studies suggest that NOTCH signaling can promote epithelial-mesenchymal
      transitions and augment signaling through AKT, an important growth and survival
      pathway in epithelial cells and prostate cancer in particular. Here we show that
      JAGGED1, a NOTCH receptor ligand, is significantly more highly expressed in
      metastatic prostate cancer as compared with localized prostate cancer or benign
      prostatic tissues, based on immunohistochemical analysis of JAGGED1 expression in
      human tumor samples from 154 men. Furthermore, high JAGGED1 expression in a
      subset of clinically localized tumors was significantly associated with
      recurrence, independent of other clinical parameters. These findings support a
      model in which dysregulation of JAGGED1 protein levels plays a role in prostate
      cancer progression and metastasis and suggest that JAGGED1 may be a useful marker
      in distinguishing indolent and aggressive prostate cancers.

PMID- 15466173
TI  - Convection-enhanced delivery of tumor necrosis factor-related apoptosis-inducing
      ligand with systemic administration of temozolomide prolongs survival in an
      intracranial glioblastoma xenograft model.
AB  - Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a
      potent activator of cell death, preferentially killing neoplastic cells over
      normal cells, the efficacy of TRAIL for the treatment of glioma might be limited
      due to cellular resistance and, importantly, poor distribution after systemic
      administration. TRAIL and temozolomide (TMZ) were recently shown to have a
      synergistic antitumor effect against U87MG glioma cells in vitro. Convection
      enhanced delivery (CED) can effectively distribute TRAIL protein throughout a
      brain tumor mass. In this study, we evaluated CED of TRAIL, alone and in
      conjunction with systemic TMZ administration, for antitumor efficacy. CED of
      TRAIL demonstrated safe and effective distribution in both normal brain and a
      U87MG intracranial xenograft model. Individually, both CED of TRAIL and systemic
      TMZ administration prolonged survival in tumor-bearing rats. However, the
      combination of these two treatments was significantly more effective than either
      treatment alone. CED of TRAIL in conjunction with systemic TMZ treatment is a
      promising strategy for the treatment of malignant gliomas.

PMID- 15466174
TI  - p73 G4C14-to-A4T14 polymorphism and risk of lung cancer.
AB  - Genetic variants in genes controlling cellular processes such as cell cycle, DNA
      repair, and apoptosis may modulate lung cancer risk. p73 has some p53-like
      activity and plays an important role in modulating these processes. The noncoding
      region of exon 2 of the p73 gene has two polymorphisms that are in complete
      linkage disequilibrium with one another, which may alter translation efficiency
      of the p73 protein. To test the hypothesis that this p73 polymorphism plays a
      role in the etiology of lung cancer, we conducted a hospital-based case-control
      study of 1054 patients newly diagnosed with lung cancer and 1139 cancer-free
      controls and evaluated the association between the p73 variant AT allele and risk
      of lung cancer. Cancer-free controls were frequency matched to the cases by age
      (+/-5 years), sex, and smoking status, and all subjects were non-Hispanic whites.
      The variant AT allele and genotypes were more common among the cases than among
      the controls (P = 0.0007 and P < 0.001, respectively). Compared with the GC/GC
      genotype, the variant GC/AT and AT/AT genotypes were associated with a
      statistically significantly increased risk for lung cancer [adjusted odds ratio
      (OR) = 1.32, 95% confidence interval (CI), 1.10-1.59 and OR = 1.54, 95% CI, 1.05
      2.26, respectively] in an allele dose-effect relationship (trend test: P <
      0.001). The risk associated with the AT allele (GC/AT+AT/AT) was more pronounced
      in younger (</=50 years) individuals (OR = 1.53, 95% CI, 1.00-2.37), men (OR =
      1.61, 95% CI, 1.26-2.06), light smokers (OR = 1.58, 95% CI, 1.17-2.14), and
      squamous cell lung carcinoma (OR = 1.79, 95% CI, 1.32-2.42). These results
      suggest that this p73 polymorphism may be a marker for susceptibility to lung
      cancer.

PMID- 15466175
TI  - Monoallelic methylation of the APC promoter is altered in normal gastric mucosa
      associated with neoplastic lesions.
AB  - Adenomatous polyposis coli (APC) promoter hypermethylation has been reported
      frequently in normal gastric mucosa, but it remained to be clarified whether this
      occurs in every individual. In this study, methylation of the APC promoter was
      analyzed in histologically normal-appearing gastric mucosa samples by methylation
      sensitive single-strand conformation analysis and by a methylation-sensitive dot
      blot assay. Epithelial cell samples were collected by microdissection from tissue
      sections. Equal amounts of methylated and unmethylated APC alleles were found in
      all gastric mucosa samples from patients without any gastric lesions (20
      samples). Allele-specific methylation analysis showed that the methylation of the
      APC promoter was monoallelic; however, which allele was methylated depended on
      the cell type. Increased or decreased methylation was found in 10 of 36 (28%)
      normal gastric mucosa samples adjacent to a gastric or esophageal adenocarcinoma.
      No allelic loss was found at the APC locus. Modification of the methylation
      status was also found in 3 of 21 (14%) normal-appearing gastric mucosa samples
      adjacent to intestinal metaplasia. In contrast, all normal mucosa samples in
      cases with chronic gastritis but without metaplasia or dysplasia showed a
      monoallelic methylation pattern. Our results indicate the following: (a) In
      normal gastric mucosa, the APC promoter shows monoallelic methylation, which is
      not due to imprinting but most likely due to allelic exclusion; (b) the excluded
      allele differs between foveolar and glandular epithelial cells; (c) the APC
      methylation pattern is frequently altered in normal-appearing gastric mucosa of
      gastric or esophageal adenocarcinoma patients; and (d) such alterations also
      occur in normal gastric mucosa adjacent to intestinal metaplasia.

PMID- 15466176
TI  - Growth factor independence-1 is expressed in primary human neuroendocrine lung
      carcinomas and mediates the differentiation of murine pulmonary neuroendocrine
      cells.
AB  - Human small cell lung cancers might be derived from pulmonary cells with a
      neuroendocrine phenotype. They are driven to proliferate by autocrine and
      paracrine neuropeptide growth factor stimulation. The molecular basis of the
      neuroendocrine phenotype of lung carcinomas is relatively unknown. The Achaete
      Scute Homologue-1 (ASH1) transcription factor is critically required for the
      formation of pulmonary neuroendocrine cells and is a marker for human small cell
      lung cancers. The Drosophila orthologues of ASH1 (Achaete and Scute) and the
      growth factor independence-1 (GFI1) oncoprotein (Senseless) genetically interact
      to inhibit Notch signaling and specify fly sensory organ development. Here, we
      show that GFI1, as with ASH1, is expressed in neuroendocrine lung cancer cell
      lines and that GFI1 in lung cancer cell lines functions as a DNA-binding
      transcriptional repressor protein. Forced expression of GFI1 potentiates tumor
      formation of small-cell lung carcinoma cells. In primary human lung cancer
      specimens, GFI1 expression strongly correlates with expression of ASH1, the
      neuroendocrine growth factor gastrin-releasing peptide, and neuroendocrine
      markers synaptophysin and chromogranin A (P < 0.0000001). GFI1 colocalizes with
      chromogranin A and calcitonin-gene-related peptide in embryonic and adult murine
      pulmonary neuroendocrine cells. In addition, mice with a mutation in GFI1 display
      abnormal development of pulmonary neuroendocrine cells, indicating that GFI1 is
      important for neuroendocrine differentiation.

PMID- 15466177
TI  - Prediction of clinical outcome using gene expression profiling and artificial
      neural networks for patients with neuroblastoma.
AB  - Currently, patients with neuroblastoma are classified into risk groups (e.g.,
      according to the Children's Oncology Group risk-stratification) to guide
      physicians in the choice of the most appropriate therapy. Despite this careful
      stratification, the survival rate for patients with high-risk neuroblastoma
      remains <30%, and it is not possible to predict which of these high-risk patients
      will survive or succumb to the disease. Therefore, we have performed gene
      expression profiling using cDNA microarrays containing 42,578 clones and used
      artificial neural networks to develop an accurate predictor of survival for each
      individual patient with neuroblastoma. Using principal component analysis we
      found that neuroblastoma tumors exhibited inherent prognostic specific gene
      expression profiles. Subsequent artificial neural network-based prognosis
      prediction using expression levels of all 37,920 good-quality clones achieved 88%
      accuracy. Moreover, using an artificial neural network-based gene minimization
      strategy in a separate analysis we identified 19 genes, including 2 prognostic
      markers reported previously, MYCN and CD44, which correctly predicted outcome for
      98% of these patients. In addition, these 19 predictor genes were able to
      additionally partition Children's Oncology Group-stratified high-risk patients
      into two subgroups according to their survival status (P = 0.0005). Our findings
      provide evidence of a gene expression signature that can predict prognosis
      independent of currently known risk factors and could assist physicians in the
      individual management of patients with high-risk neuroblastoma.

PMID- 15466178
TI  - Genetic pathways to glioblastoma: a population-based study.
AB  - We conducted a population-based study on glioblastomas in the Canton of Zurich,
      Switzerland (population, 1.16 million) to determine the frequency of major
      genetic alterations and their effect on patient survival. Between 1980 and 1994,
      715 glioblastomas were diagnosed. The incidence rate per 100,000 population/year,
      adjusted to the World Standard Population, was 3.32 in males and 2.24 in females.
      Observed survival rates were 42.4% at 6 months, 17.7% at 1 year, and 3.3% at 2
      years. For all of the age groups, younger patients survived significantly longer,
      ranging from a median of 8.8 months (<50 years) to 1.6 months (>80 years). Loss
      of heterozygosity (LOH) 10q was the most frequent genetic alteration (69%),
      followed by EGFR amplification (34%), TP53 mutations (31%), p16(INK4a) deletion
      (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the
      other genetic alterations and was predictive of shorter survival. Primary (de
      novo) glioblastomas prevailed (95%), whereas secondary glioblastomas that
      progressed from low-grade or anaplastic gliomas were rare (5%). Secondary
      glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations
      (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hotspot
      codons 248 and 273, whereas in primary glioblastomas, mutations were more equally
      distributed. G:C-->A:T mutations at CpG sites were more frequent in secondary
      than primary glioblastomas (56% versus 30%; P = 0.0208). This suggests that the
      acquisition of TP53 mutations in these glioblastoma subtypes occurs through
      different mechanisms.

PMID- 15466179
TI  - Maspin expression is transactivated by p63 and is critical for the modulation of
      lung cancer progression.
AB  - Maspin inhibits metastasis of some cancer cells, and clinical studies have
      identified correlations between maspin loss and poor prognosis in several cancer
      types. Maspin was found to be significantly overexpressed in lung cancer samples
      as compared with matched normal lung tissues. However, the regulatory mechanism
      of maspin expression remains unclear. We show here that differential expression
      of maspin in carcinoma-derived lung cancer cells is regulated at the
      transcriptional level. We found that p63 is a critical factor for the
      transcription of maspin, which is lost in highly invasive cancer cells such as
      NCI-H157, NCI-322, and NCI-358. No correlation was found between maspin
      expression and the previously associated transcription factors, p53, Ets1, and
      Pdef. Instead, maspin expression was strictly dependent on the presence of p63 in
      lung cancer tissues (P < 0.001) and in the tested cell lines. Transient
      expression of p63 transactivated the maspin promoter with remarkable fold changes
      in cells expressing the TAp63, suggesting that TAp63 might be a novel stimulator
      of the maspin promoter in lung cancer. We have also demonstrated the binding of
      p63 protein to a previously identified p53-binding site on the maspin promoter by
      gel shift and chromatin immunoprecipitation assays. In tumor tissues, maspin
      expression was associated with lymph node involvement (P = 0.035) and tumor stage
      (P = 0.063) in all tested cases, except squamous carcinoma. In terms of function,
      ectopic expression of maspin inhibited cell invasion in squamous carcinoma as
      well as adenocarcinoma. Taken together, these results define maspin as a new
      molecular target of p63 that eventually inhibits the invasion of lung cancer.

PMID- 15466180
TI  - PTEN gene targeting reveals a radiation-induced size checkpoint in human cancer
      cells.
AB  - Following DNA damage, human cells arrest primarily in the G(1) and G(2) phases of
      the cell cycle. Here, we show that after irradiation, human cancer cells with
      targeted deletion of PTEN or naturally occurring PTEN mutations can exert G(1)
      and G(2) arrests but are unable to arrest in size. Pharmacological inhibition of
      phosphoinositol-3-kinase or mTOR in PTEN(-/-) cells restored the size arrest,
      whereas siRNA-mediated depletion of TSC2 in PTEN(+/+) cells attenuated the size
      arrest. Radiation treatment potentiated Akt activation in PTEN(-/-) but not
      PTEN(+/+) cells. Finally, abrogation of the size arrest via PTEN deletion
      conferred radiosensitivity both in vitro and in vivo. These results identify a
      new tumor suppressor gene-regulated, DNA damage-inducible arrest that occurs
      simultaneously with the G(1) and G(2) arrests but is genetically separable from
      them. We suggest that aberrant regulation of cell size during cell cycle arrest
      may be important in human cancer pathogenesis.

PMID- 15466181
TI  - Mutations of BRAF and KRAS precede the development of ovarian serous borderline
      tumors.
AB  - Molecular genetic changes that are associated with the initiating stage of tumor
      development are important in tumorigenesis. Ovarian serous borderline tumors
      (SBTs), putative precursors of low-grade serous carcinomas, are among the few
      human neoplasms with a high frequency of activating mutations in BRAF and KRAS
      genes. However, it remains unclear as to how these mutations contribute to tumor
      progression. To address this issue, we compared the mutational status of BRAF and
      KRAS in both SBTs and the adjacent epithelium from cystadenomas, the presumed
      precursor of SBTs. We found that three of eight SBTs contained mutant BRAF, and
      four SBTs contained mutant KRAS. All specimens with mutant BRAF harbored wild
      type KRAS and vice versa. Thus, seven (88%) of eight SBTs contained either BRAF
      or KRAS mutations. The same mutations detected in SBTs were also identified in
      the cystadenoma epithelium adjacent to the SBTs in six (86%) of seven informative
      cases. As compared to SBTs, the cystadenoma epithelium, like ovarian surface
      epithelium, lacks cytological atypia. Our findings provide cogent evidence that
      mutations of BRAF and KRAS occur in the epithelium of cystadenomas adjacent to
      SBTs and strongly suggest that they are very early events in tumorigenesis,
      preceding the development of SBT.

PMID- 15466182
TI  - Spontaneous mutations in digestive tract of old mice show tissue-specific
      patterns of genomic instability.
AB  - In an attempt to evaluate the possible role of mutations in the age-dependent
      increase of tumor incidence, we studied the mutational burden that accumulates in
      the aging process in different parts of the digestive tract in mice. The
      mutations were monitored in lacZ genes integrated in the mouse genome. The
      digestive tract was divided into the esophagus, stomach, proximal, medial, and
      distal part of the small intestine, and the colon. Epithelial tissues were
      separated from these tissues with the exception of the esophagus, in which case
      the whole tissue was examined. At a young age, the mutant frequencies as well as
      the molecular nature of the mutations were similar among the tissues examined. In
      old age, on the other hand, mutant frequencies were elevated to different degrees
      among the tissues; they were high in the small intestine and colon, intermediate
      in the stomach, and low in the esophagus. The molecular characteristics of the
      mutations also revealed distinct tissue-specificity; there were elevated rates of
      a small deletion mutation in the esophagus, G:C to T:A transversion in the
      proximal small intestine, and multiple mutations in the distal small intestine
      and colon. The results indicate that different parts of the digestive tract
      suffer from different kinds of mutational stress in the aging process. The nature
      of the multiple mutations suggests the presence of a mutator phenotype based on
      an imbalance in deoxyribonucleotide pools.

PMID- 15466183
TI  - Inhibition of gp130 signaling in breast cancer blocks constitutive activation of
      Stat3 and inhibits in vivo malignancy.
AB  - The cytokine receptor gp130 is the common signaling subunit of receptors used by
      the interleukin (IL)-6 cytokine family. gp130 is widely expressed in breast
      cancer cell lines and primary tumors. The role of gp130 in breast cancer in vivo
      is unknown. To study the effect of gp130 inhibition in breast cancer, endogenous
      gp130 signaling in breast cancer cell lines was blocked with a dominant-negative
      gp130 protein (DN gp130). DN gp130 inhibited constitutive Stat3 activation in
      breast cancer cells. Both gp130 and epidermal growth factor receptor (EGFR) have
      been implicated in constitutive Stat3 activation in breast cancer. There are
      known physical and functional interactions between gp130 and EGFR. Consistent
      with this, we show that DN gp130 inhibits signaling downstream of the EGFR in
      breast cancer cells. The effect of DN gp130 on breast cancer in vivo was assessed
      with an orthotopic nude mouse model. DN gp130 MDA-231 cells had markedly
      decreased engraftment, size, and metastasis compared with control cells. These
      results are particularly striking considering that DN gp130-expressing breast
      cancer cells grow faster in vitro. We hypothesized that DN gp130 expression
      results in inhibition of invasion and metastasis in vivo. Marked angiogenesis was
      present in tumors from control animals and was absent in tumors from DN gp130
      animals. We additionally show that tissue inhibitor of metalloproteinase-3, an
      inhibitor of tumor invasion and angiogenesis, is up-regulated in both MDA-231 DN
      gp130 cells and tumors. These results, in light of the availability of several
      potential pharmacological inhibitors of gp130, suggest novel approaches to breast
      cancer therapy.

PMID- 15466184
TI  - Oncogenic action of secreted phospholipase A2 in prostate cancer.
AB  - Mortality from prostate cancer is associated with progression of tumors to
      androgen-independent growth and metastasis. Eicosanoid products of both the
      cyclooxygenase (COX) and lipoxygenase (LOX) pathways are important mediators of
      the proliferation of prostate cancer cells in culture and regulate tumor
      vascularization and metastasis in animal models. Pharmacologic agents that block
      either COX or LOX products effectively reduce the size of prostate cancer
      xenografts. Phospholipase A(2) (PLA(2)) enzymes regulate the provision of
      arachidonic acid to both COX- and LOX-derived eicosanoids, and a secreted form of
      the enzyme (sPLA(2)-IIA) is elevated in prostate cancer tissues. Here, we show by
      immunohistochemistry, in patients receiving androgen ablation therapy, that
      sPLA(2)-IIA remains elevated in remaining cancer cells relative to benign glands
      after treatment. Furthermore, sPLA(2)-IIA expression seen in benign glands is
      substantially decreased after androgen depletion, whereas cytosolic PLA(2)-alpha
      (cPLA(2)-alpha) levels are unchanged. sPLA(2)-IIA mRNA expression is detectable
      and inducible by androgen (0.01-10 nmol/L) in the androgen-sensitive cell line
      LNCaP, and exogenous addition of sPLA(2)-IIA (1-100 nmol/L), but not an inactive
      sPLA(2)-IIA mutant (H(48)Q), results in a dose-dependent increase in cell numbers
      or the fraction of cells in G(2)-M phase, which is inhibited by sPLA(2)-IIA
      selective inhibitors. The effect of exogenous sPLA(2)-IIA can also be blocked by
      inhibition of cPLA(2)-alpha, suggesting a role for cPLA(2)-alpha in mediating
      sPLA(2)-IIAlpha action. sPLA(2)-IIA inhibitors suppressed basal proliferation in
      LNCaP cells and in the androgen-independent, sPLA(2)-positive cell line PC3 but
      not in the sPLA(2)-IIA-negative androgen-independent cell line DU145. Established
      PC3 xenograft tumors grew more slowly in mice treated with sPLA(2)-IIA inhibitors
      than those treated with saline only. The PLA(2) enzymes, and sPLA(2)-IIA in
      particular, thus represent important targets for the treatment of sPLA(2)-IIA
      positive androgen-independent prostate cancer.

PMID- 15466185
TI  - Chromosome transfer induced aneuploidy results in complex dysregulation of the
      cellular transcriptome in immortalized and cancer cells.
AB  - Chromosomal aneuploidies are observed in essentially all sporadic carcinomas.
      These aneuploidies result in tumor-specific patterns of genomic imbalances that
      are acquired early during tumorigenesis, continuously selected for and faithfully
      maintained in cancer cells. Although the paradigm of translocation induced
      oncogene activation in hematologic malignancies is firmly established, it is not
      known how genomic imbalances affect chromosome-specific gene expression patterns
      in particular and how chromosomal aneuploidy dysregulates the genetic equilibrium
      of cells in general. To model specific chromosomal aneuploidies in cancer cells
      and dissect the immediate consequences of genomic imbalances on the
      transcriptome, we generated artificial trisomies in a karyotypically stable
      diploid yet mismatch repair-deficient, colorectal cancer cell line and in
      telomerase immortalized, cytogenetically normal human breast epithelial cells
      using microcell-mediated chromosome transfer. The global consequences on gene
      expression levels were analyzed using cDNA arrays. Our results show that
      regardless of chromosome or cell type, chromosomal trisomies result in a
      significant increase in the average transcriptional activity of the trisomic
      chromosome. This increase affects the expression of numerous genes on other
      chromosomes as well. We therefore postulate that the genomic imbalances observed
      in cancer cells exert their effect through a complex pattern of transcriptional
      dysregulation.

PMID- 15466186
TI  - Gene expression profiling of tumor-stromal interactions between pancreatic cancer
      cells and stromal fibroblasts.
AB  - The interactions between cancer cells and surrounding stroma play a critical role
      in tumor progression, but their molecular basis is largely unknown. Global gene
      expression profiling was performed using oligonucleotide microarrays to determine
      changes in the gene expression of pancreatic cancer cells (CFPAC1) and stromal
      fibroblasts induced by coculture. This analysis identified multiple genes as
      differentially expressed in pancreatic cancer cells and in fibroblasts as a
      consequence of their mutual interactions, including those that encode for
      proteins associated with tumor invasion, metastasis, and angiogenesis. Among the
      genes identified, the cyclooxygenase-2 (COX-2)/PTGS2 gene was of particular
      interest because COX-2 expression was markedly augmented in both cell types
      (cancer cells and fibroblasts) in response to coculture. Coculture with
      fibroblasts also induced COX-2 expression in additional pancreatic cancer cells
      with an unmethylated COX-2 promoter, but not in those with a methylated COX-2
      promoter. Using an in vitro invasion assay, we found an increase in the invasive
      potential of CFPAC1 cells when they were cocultured with fibroblasts, an effect
      blocked partially by the addition of a selective COX-2 inhibitor, NS-398, or by
      COX-2 knockdown with small interfering RNA. Thus, COX-2 inhibitors can decrease
      the invasive properties of pancreatic cancer cells acquired through tumor-stromal
      interactions.

PMID- 15466187
TI  - Cystatin m: a novel candidate tumor suppressor gene for breast cancer.
AB  - The contribution of pericellular proteolysis to tumor progression is well
      documented. To better understand protease biology and facilitate clinical
      translation, specific proteolytic systems need to be better defined. In
      particular, the precise role of endogenous protease inhibitors still needs to be
      deciphered. We reported previously that cystatin M, a potent endogenous inhibitor
      of lysosomal cysteine proteases, significantly suppressed in vitro cell
      proliferation, migration, and Matrigel invasion. Here, we show that scid mice
      orthotopically implanted with breast cancer cells expressing cystatin M show
      significantly delayed primary tumor growth and lower metastatic burden in the
      lungs and liver when compared with mice implanted with mock controls. The
      incidence of metastasis, however, appeared to be unaltered between the cystatin M
      group and the control group. Experimental metastasis assays suggest that cystatin
      M suppressed tumor cell proliferation at the secondary site. By using laser
      capture microdissection and quantitative reverse transcription-polymerase chain
      reaction, we found consistent expression of cystatin M in normal human breast
      epithelial cells, whereas expression was decreased by 86% in invasive ductal
      carcinoma (IDC) cells of stage I to IV patients. Complete loss of expression of
      cystatin M was observed in two of three IDCs from stage IV patients.
      Immunohistochemical studies confirmed that expression of cystatin M in IDCs was
      partially or completely lost. We propose cystatin M as a novel candidate tumor
      suppressor gene for breast cancer.

PMID- 15466188
TI  - A protective role for matrix metalloproteinase-3 in squamous cell carcinoma.
AB  - Elevated expression of matrix metalloproteinase-3 (MMP-3/stromelysin-1) is
      associated with a variety of tumor types, although its in vivo functional role
      remains unclear. In human and murine squamous cell carcinoma (SCC), MMP-3 is
      expressed in the stromal compartment at all of the stages of tumor progression
      and is expressed by the malignant epithelial cells in late-stage, highly invasive
      tumors. To elucidate whether MMP-3 plays a causal role during SCC, wild-type and
      MMP-3 null mice were subjected to chemical carcinogenesis procedures by topical
      application of either the complete carcinogen 1-methyl-3-nitro-1-nitroso
      guanidine or two-stage initiation and promotion with 7,12
      dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. Contrasting
      with our expectations, tumors originating on MMP-3 null mice had enhanced initial
      tumor growth rates as compared with control animals, although there was no
      difference in tumor onset or incidence. This elevated rate in growth was coupled
      with an elevated proliferative index and a reduced vasculature density but with
      no significant effect on apoptosis. Tumors from MMP-3 null mice had a prevalence
      of undifferentiated spindle tumors as compared with controls, which was
      concomitant with a higher percentage of MMP-3 null mice evidencing surface lung
      metastases. Tumor progression in MMP-3 null mice was inversely associated with
      leukocyte infiltration, in which an overall reduction in tumor-associated
      macrophages and neutrophils was evident. We propose that MMP-3 is expressed as a
      protective response and plays an important role in host defense during SCC
      tumorigenesis.

PMID- 15466189
TI  - Down-regulation of the homeodomain factor Cdx2 in colorectal cancer by collagen
      type I: an active role for the tumor environment in malignant tumor progression.
AB  - The homeobox transcription factor Cdx2 specifies intestinal development and
      homeostasis and is considered a tumor suppressor in colorectal carcinogenesis.
      However, Cdx2 mutations are rarely found. Invasion of colorectal cancer is
      characterized by a transient loss of differentiation and nuclear accumulation of
      the oncoprotein beta-catenin in budding tumor cells. Strikingly, this is reversed
      in growing metastases, indicating that tumor progression is a dynamic process
      that is not only driven by genetic alterations but also regulated by the tumor
      environment. Here we describe a transient loss of Cdx2 in budding tumor cells at
      the tumor host interface, and reexpression of Cdx2 in metastases. Cell culture
      experiments show that collagen type I, through beta(1) integrin signaling,
      triggers a transient transcriptional down-regulation of Cdx2 and its intestine
      specific target gene sucrase isomaltase, associated with a loss of
      differentiation. These data indicate an active role for the tumor environment in
      malignant tumor progression.

PMID- 15466190
TI  - Signaling and transcriptional changes critical for transformation of human cells
      by simian virus 40 small tumor antigen or protein phosphatase 2A B56gamma
      knockdown.
AB  - One set of genes sufficient for transformation of primary human cells uses the
      combination of Ha-Ras-V12, the telomerase catalytic subunit hTERT, SV40 large
      tumor antigen (LT), and SV40 small tumor antigen (ST). Whereas SV40 LT
      inactivates the retinoblastoma protein and p53, the contribution of ST is poorly
      understood. The essential helper function of ST requires a functional interaction
      with protein phosphatase 2A (PP2A). Here we have identified changes in gene
      expression induced by ST and show that ST mediates these changes through both
      PP2A-dependent and PP2A-independent mechanisms. Knockdown of PP2A B56gamma
      subunit can substitute for ST expression to fully transform cells expressing LT,
      hTERT, and Ras-V12. We also identify those genes affected similarly in two cell
      lines that have been fully transformed from a common parental line by two
      alternative mechanisms, namely ST expression or PP2A B56gamma subunit knockdown.
      ST altered expression of genes involved in proliferation, apoptosis, integrin
      signaling, development, immune responses, and transcriptional regulation. ST
      reduced surface expression of MHC class I molecules, consistent with a need for
      SV40 to evade immune detection. ST expression enabled cell cycle progression in
      reduced serum and src phosphorylation in anchorage-independent media, whereas
      B56gamma knockdown required normal serum levels for these phenotypes. Inhibitors
      of integrin and src signaling prevented anchorage-independent growth of
      transformed cells, suggesting that integrin and src activation are key ST
      mediated events in transformation. Our data support a model in which ST promotes
      survival through constitutive integrin signaling, src phosphorylation, and
      nuclear factor kappaB activation, while inhibiting cell-cell adhesion pathways.

PMID- 15466191
TI  - Dysadherin expression facilitates cell motility and metastatic potential of human
      pancreatic cancer cells.
AB  - Dysadherin is a membrane glycoprotein expressed strongly in several human
      cancers. Overexpression of dysadherin in tumor cells is closely associated with
      malignant phenotype (e.g., metastasis) and poor prognosis. In our analysis, six
      pancreatic cancer cell lines showed a positive correlation between dysadherin
      expression and cell motility. Introduction of small interfering RNA (siRNA)
      against dysadherin into the Panc-1 cell line caused reduction of dysadherin
      expression and suppression of cell motility. In contrast, stable transfection of
      a dysadherin expression vector into the Capan-1 cell line increased cell
      motility. In vivo, the metastatic potential of orthotopically transplanted Capan
      1 tumor cells in severe combined immunodeficient mice was increased by dysadherin
      overexpression. Cell morphology and actin organization were also influenced by
      modulation of dysadherin expression. Cells transfected with dysadherin siRNA
      tended to have a relatively larger, more spread shape and increased transverse
      actin stress fibers compared with parent cells and cells transfected with control
      siRNA. Our study suggests that dysadherin is able to modulate actin structures,
      stimulate cell motility, and contribute directly to the metastatic potential of
      human pancreatic cancer cells.

PMID- 15466192
TI  - Ether a go-go potassium channels as human cervical cancer markers.
AB  - Ether a go-go (EAG) potassium channels display oncogenic properties. In normal
      tissues, EAG mRNA is almost exclusively expressed in brain, but it is expressed
      in several somatic cancer cell lines, including HeLa, from cervix. Antisense
      experiments against eag reduce cell proliferation in some cancer cell lines, and
      inhibition of EAG-mediated currents has been suggested to decrease cell
      proliferation in a melanoma cell line. Because of the potential clinical
      relevance of EAG, we investigated EAG mRNA expression in the following fresh
      samples from human uterine cervix: 5 primary cultures obtained from cancerous
      biopsies, 1 cancerous fresh tissue, and 12 biopsies of control normal tissue. All
      of the control cervical samples came from patients with negative pap smears.
      Reverse transcription-PCR and Southern-blot experiments revealed eag expression
      in 100% of the cancerous samples and in 33% of the normal biopsies.
      Immunochemistry experiments showed the presence of EAG channel protein in cells
      from the primary cultures and in cervical cancer biopsies sections from the same
      patients. In addition, we looked for EAG-mediated currents in the cultures from
      cervical cancer cells. Here we show for the first time EAG channel activity in
      human tumors. Patch-clamp recordings showed typical EAG-mediated currents
      modulated by magnesium and displaying a pronounced Cole-Moore shift. Because EAG
      expression and channel activity have been suggested to be important in cell
      proliferation, our findings strongly support the idea of considering EAG as a
      tumor marker as well as a potential membrane therapeutic target for cervical
      cancer.

PMID- 15466193
TI  - Deregulated Akt3 activity promotes development of malignant melanoma.
AB  - Malignant melanoma is the skin cancer with the most significant impact on man,
      carrying the highest risk of death from metastasis. Both incidence and mortality
      rates continue to rise each year, with no effective long-term treatment on the
      horizon. In part, this reflects lack of identification of critical genes involved
      and specific therapies targeted to correct these defects. We report that
      selective activation of the Akt3 protein promotes cell survival and tumor
      development in 43 to 60% of nonfamilial melanomas. The predominant Akt isoform
      active in melanomas was identified by showing that small interfering RNA (siRNA)
      against only Akt3, and not Akt1 or Akt2, lowered the amount of phosphorylated
      (active) Akt in melanoma cells. The amount of active Akt3 increased progressively
      during melanoma tumor progression with highest levels present in advanced-stage
      metastatic melanomas. Mechanisms of Akt3 deregulation occurred through a
      combination of overexpression of Akt3 accompanying copy number increases of the
      gene and decreased PTEN protein function occurring through loss or
      haploinsufficiency of the PTEN gene. Targeted reduction of Akt3 activity with
      siRNA or by expressing active PTEN protein stimulated apoptotic signaling, which
      reduced cell survival by increasing apoptosis rates thereby inhibiting melanoma
      tumor development. Identifying Akt3 as a selective target in melanoma cells
      provides new therapeutic opportunities for patients in the advanced stages of
      this disease.

PMID- 15466194
TI  - Isolation and characterization of tumorigenic, stem-like neural precursors from
      human glioblastoma.
AB  - Transformed stem cells have been isolated from some human cancers. We report
      that, unlike other brain cancers, the lethal glioblastoma multiforme contains
      neural precursors endowed with all of the critical features expected from neural
      stem cells. Similar, yet not identical, to their normal neural stem cell
      counterpart, these precursors emerge as unipotent (astroglial) in vivo and
      multipotent (neuronal-astroglial-oligodendroglial) in culture. More importantly,
      these cells can act as tumor-founding cells down to the clonal level and can
      establish tumors that closely resemble the main histologic, cytologic, and
      architectural features of the human disease, even when challenged through serial
      transplantation. Thus, cells possessing all of the characteristics expected from
      tumor neural stem cells seem to be involved in the growth and recurrence of adult
      human glioblastomas multiforme.

PMID- 15466195
TI  - A paracrine loop between tumor cells and macrophages is required for tumor cell
      migration in mammary tumors.
AB  - Invasion of tumor cells into the surrounding connective tissue and blood vessels
      is a key step in the metastatic spread of breast tumors. Although the presence of
      macrophages in primary tumors is associated with increased metastatic potential,
      the mechanistic basis for this observation is unknown. Using a chemotaxis-based
      in vivo invasion assay and multiphoton-based intravital imaging, we show that the
      interaction between macrophages and tumor cells facilitates the migration of
      carcinoma cells in the primary tumor. Gradients of either epidermal growth factor
      (EGF) or colony-stimulating factor 1 (CSF-1) stimulate collection into
      microneedles of tumor cells and macrophages even though tumor cells express only
      EGF receptor and macrophages express only CSF-1 receptor. Intravital imaging
      shows that macrophages and tumor cells migrate toward microneedles containing
      either EGF or CSF-1. Inhibition of either CSF-1- or EGF-stimulated signaling
      reduces the migration of both cell types. This work provides the first direct
      evidence for a synergistic interaction between macrophages and tumor cells during
      cell migration in vivo and indicates a mechanism for how macrophages may
      contribute to metastasis.

PMID- 15466196
TI  - Regulation of alpha-fetoprotein by nuclear factor-kappaB protects hepatocytes
      from tumor necrosis factor-alpha cytotoxicity during fetal liver development and
      hepatic oncogenesis.
AB  - Nuclear factor-kappaB (NF-kappaB) plays a critical role during fetal liver
      development and hepatic oncogenesis. Here, we have assessed whether NF-kappaB
      activity is required for murine hepatocellular carcinoma cell survival. We show
      that adenoviral-mediated inhibition of inhibitor of NF-kappaB kinase-beta (IKK-2)
      activity in hepatocellular carcinomas derived from transforming growth factor
      (TGF)-alpha/c-myc bitransgenic mice leads to inhibition of NF-kappaB and promotes
      tumor necrosis factor (TNF)-alpha-mediated cell death of malignant hepatocytes
      but not the surrounding peritumorous tissue. Induction of apoptosis is
      accompanied by inhibition of Bcl-X(L) and XIAP, two pro-survival NF-kappaB target
      genes. In addition, we have identified the alpha-fetoprotein (AFP) as a novel
      downstream target of NF-kappaB. We show that repression of IKK-2 activity in
      hepatocellular carcinomas promotes down-regulation of AFP gene expression.
      Likewise, genetic disruption of the RelA subunit results in reduced AFP gene
      expression during embryonic liver development, at a time in which fetal
      hepatocytes are sensitized to TNF-alpha-mediated cell killing. In this regard, we
      show that AFP inhibits TNF-alpha-induced cell death of murine hepatocellular
      carcinomas through association with TNF-alpha and inhibition of TNFRI signaling.
      Thus, NF-kappaB-mediated regulation of AFP gene expression during liver tumor
      formation and embryonic development of the liver constitutes a potential novel
      mechanism used by malignant and fetal hepatocytes to evade immune surveillance.

PMID- 15466197
TI  - Pancreatic insulinomas in multiple endocrine neoplasia, type I knockout mice can
      develop in the absence of chromosome instability or microsatellite instability.
AB  - Multiple endocrine neoplasia, type I (MEN1) is an inherited cancer syndrome
      characterized by tumors arising primarily in endocrine tissues. The responsible
      gene acts as a tumor suppressor, and tumors in affected heterozygous individuals
      occur after inactivation of the wild-type allele. Previous studies have shown
      that Men1 knockout mice develop multiple pancreatic insulinomas, but this occurs
      many months after loss of both copies of the Men1 gene. These studies imply that
      loss of Men1 is not alone sufficient for tumor formation and that additional
      somatic genetic changes are most likely essential for tumorigenesis. The usual
      expectation is that such mutations would arise either by a chromosomal
      instability or microsatellite instability mechanism. In a study of more then a
      dozen such tumors, using the techniques of array-based comparative genomic
      hybridization, fluorescent in situ hybridization, loss of heterozygosity analysis
      using multiple microsatellite markers across the genome, and real time PCR to
      assess DNA copy number, it appears that many of these full-blown clonal adenomas
      remain remarkably euploid. Furthermore, the loss of the wild-type Men1 allele in
      heterozygous Men1 mice occurs by loss and reduplication of the entire mutant
      bearing chromosome. Thus, the somatic genetic changes that are postulated to lead
      to tumorigenesis in a mouse model of MEN1 must be unusually subtle, occurring at
      either the nucleotide level or through epigenetic mechanisms.

PMID- 15466198
TI  - Proinvasive properties of ovarian cancer ascites-derived membrane vesicles.
AB  - Malignant ovarian ascites are rich in cellular components, membrane-bound
      vesicles, and soluble proteins. This study focused on the structure of membrane
      bound vesicles and their ability to promote invasion in cultured malignant
      ovarian epithelium. Membrane vesicles were derived from women with stage I-IV
      malignant ovarian ascites and from nonmalignant gynecologic ascites. Isolated
      vesicles were characterized by immunofluorescence and Western blot analysis.
      Using gel zymography for matrix metalloproteinase (MMP) detection and a
      colorimetric assay for urokinase-type plasminogen activator (uPA) analysis, we
      analyzed the proteinase activities of MMP-2, MMP-9, and uPA from the prepared
      vesicles, whole cells isolated from ascites, and the cell-free ultracentrifuged
      supernatant. The invasiveness of established cultured malignant ovarian
      epithelium on addition of ascites-derived vesicles was tested using a Matrigel
      based invasion assay. Fractionation of malignant ascites revealed that
      extracellular matrix-degrading proteinases including MMPs and uPA are localized
      preferentially in membrane vesicles. All malignant vesicles tested, regardless of
      cancer stage, stimulated invasion. Furthermore, the combination of ovarian cancer
      cells and membrane vesicles resulted in greater uPA activation than that of cells
      or vesicles alone. Membrane vesicles from malignant ascites were also found to
      contain activated MMP-2, MMP-9, and uPA. Our data suggest that vesicle-stimulated
      proteinase activation leads to increased extracellular matrix degradation, which
      may facilitate tumor cell invasion and metastasis.

PMID- 15466199
TI  - Role of the human ST6GalNAc-I and ST6GalNAc-II in the synthesis of the cancer
      associated sialyl-Tn antigen.
AB  - The Sialyl-Tn antigen (Neu5Acalpha2-6GalNAc-O-Ser/Thr) is highly expressed in
      several human carcinomas and is associated with carcinoma aggressiveness and poor
      prognosis. We characterized two human sialyltransferases, CMP-Neu5Ac:GalNAc-R
      alpha2,6-sialyltransferase (ST6GalNAc)-I and ST6GalNAc-II, that are candidate
      enzymes for Sialyl-Tn synthases. We expressed soluble recombinant hST6GalNAc-I
      and hST6GalNAc-II and characterized the substrate specificity of both enzymes
      toward a panel of glycopeptides, glycoproteins, and other synthetic
      glycoconjugates. The recombinant ST6GalNAc-I and ST6GalNAc-II showed similar
      substrate specificity toward glycoproteins and GalNAcalpha-O-Ser/Thr
      glycopeptides, such as glycopeptides derived from the MUC2 mucin and the
      HIVgp120. We also observed that the amino acid sequence of the acceptor
      glycopeptide contributes to the in vitro substrate specificity of both enzymes.
      We additionally established a gastric cell line, MKN45, stably transfected with
      the full length of either ST6GalNAc-I or ST6GalNAc-II and evaluated the
      carbohydrate antigens expression profile induced by each enzyme. MKN45
      transfected with ST6GalNAc-I showed high expression of Sialyl-Tn, whereas MKN45
      transfected with ST6GalNAc-II showed the biosynthesis of the Sialyl-6T structure
      [Galbeta1-3 (Neu5Acalpha2-6)GalNAc-O-Ser/Thr]. In conclusion, although both
      enzymes show similar in vitro activities when Tn antigen alone is available,
      whenever both Tn and T antigens are present, ST6GalNAc-I acts preferentially on
      Tn antigen, whereas the ST6GalNAc-II acts preferentially on T antigen. Our
      results show that ST6GalNAc-I is the major Sialyl-Tn synthase and strongly
      support the hypothesis that the expression of the Sialyl-Tn antigen in cancer
      cells is due to ST6GalNAc-I activity.

PMID- 15466200
TI  - Cleavage of lumican by membrane-type matrix metalloproteinase-1 abrogates this
      proteoglycan-mediated suppression of tumor cell colony formation in soft agar.
AB  - The small leucine-rich proteoglycan lumican was identified from a human placenta
      cDNA library by the expression cloning method as a gene product that interacts
      with membrane-type matrix metalloproteinase-1 (MT1-MMP). Coexpression of MT1-MMP
      with lumican in HEK293T cells reduced the concentration of lumican secreted into
      culture medium, and this reduction was abolished by addition of the MMP inhibitor
      BB94. Lumican protein from bovine cornea and recombinant lumican core protein
      fused to glutathione S-transferase was shown to be cleaved at multiple sites by
      recombinant MT1-MMP. Transient expression of lumican in HEK293 cells induced
      expression of tumor suppressor gene product p21/Waf-1, which was abrogated by the
      coexpression of MT1-MMP concomitant with a reduction in lumican concentration in
      culture medium. Stable expression of lumican in HeLa cells induced expression of
      p21 and reduction of colony formation in soft agar, which were both abolished by
      the expression of MT1-MMP. HT1080 fibrosarcoma cells stably transfected with the
      lumican cDNA (HT1080/Lum), which express endogenous MT1-MMP, secreted moderate
      levels of lumican; however, treatment of HT1080/Lum cells with BB94 resulted in
      accumulation of lumican in culture medium. The expression levels of p21 in
      HT1080/Lum were proportional to the concentration of secreted lumican and showed
      reverse corelation with colony formation in soft agar. These results suggest that
      MT1-MMP abrogates lumican-mediated suppression of tumor cell colony formation in
      soft agar by degrading this proteoglycan, which down-regulates it through the
      induction of p21.

PMID- 15466201
TI  - Apoptosis resistance of MCF-7 breast carcinoma cells to ionizing radiation is
      independent of p53 and cell cycle control but caused by the lack of caspase-3 and
      a caffeine-inhibitable event.
AB  - We have shown previously that ionizing radiation (IR) induces a persistent G(2)-M
      arrest but not cell death in MCF-7 breast carcinoma cells that harbor functional
      p53 but lack caspase-3. In the present study, we investigated the mechanisms of
      apoptosis resistance and the roles of p53, caspase-3, and cell cycle arrest in IR
      induced apoptosis. The methylxanthine caffeine and the staurosporine analog UCN
      01, which can inhibit ATM and Chk kinases, efficiently abrogated the IR-induced
      G(2)-M arrest and induced mitochondrial activation as judged by the loss of the
      mitochondrial membrane potential and the release of cytochrome c and Smac/Diablo.
      However, despite these proapoptotic alterations, cell death and activation of the
      initiator caspase-9 were not induced in MCF-7 cells but were interestingly only
      observed after reexpression of caspase-3. Sensitization to IR-induced apoptosis
      by caffeine or UCN-01 was abrogated neither by cycloheximide nor by pifithrin
      alpha, an inhibitor of the transcriptional activity of p53. Furthermore,
      suppression of p53 by RNA interference could not prevent caffeine- and IR-induced
      mitochondrial alterations and apoptosis but resulted in an even more pronounced
      G(2)-M arrest. Collectively, our results clearly show that the resistance of MCF
      7 cells to IR-induced apoptosis is caused by two independent events; one of them
      is a caffeine- or UCN-01-inhibitable event that does not depend on p53 or a
      release of the G(2)-M arrest. The second event is the loss of caspase-3 that
      surprisingly seems essential for a fully functional caspase-9 pathway, even
      despite the previous release of mitochondrial proapoptotic proteins.

PMID- 15466202
TI  - The role of defective mismatch repair in small bowel adenocarcinoma in celiac
      disease.
AB  - Celiac disease is associated with an increased risk of small bowel
      adenocarcinoma. The aims of this study were to investigate the molecular basis,
      assess outcomes, and identify clinicopathologic characteristics of small bowel
      adenocarcinoma in celiac disease. Retrospective case control cohort study of all
      celiac disease patients treated at our institution for small bowel adenocarcinoma
      and matched control patients with sporadic small bowel adenocarcinoma from July
      1960 to November 2002. Mismatch repair (MMR) status was accessed by testing
      tissue for microsatellite instability (MSI) and for hMLH1 and hMSH2 protein
      expression. Over a 40-year time period, 18 patients with small bowel
      adenocarcinoma and celiac disease were treated at the Mayo Clinic. One celiac
      disease patient was excluded. High-frequency MSI (MSI-H) was identified in 8 of
      11 (73%) and 2 of 22 (9%) available small bowel adenocarcinoma specimens in the
      celiac disease and control groups, respectively. In the celiac disease group, MSI
      H was associated with loss of hMLH1 and hMSH2 in 6 and 1 specimens, respectively.
      Loss of hMLH1 occurred in both control tumors. Stage was associated with celiac
      disease status (P = 0.018), and 78% of controls were stage III or IV compared
      with 47% of celiac disease patients. Overall, survival was better (P = 0.025) in
      the celiac disease group compared with stage-matched controls. Celiac disease
      patients with small bowel adenocarcinoma had a high incidence defective MMR (73%)
      compared with controls and had better survival compared with stage-matched
      controls. In addition, celiac disease patients presented more frequently with
      early-stage small bowel adenocarcinoma. The better survival and earlier
      presentation of small bowel adenocarcinoma in celiac disease appears to be
      biologically associated with defective MMR.

PMID- 15466203
TI  - Development of an autocrine neuregulin signaling loop with malignant
      transformation of human breast epithelial cells.
AB  - Neuregulin (NRG) is a heparin-binding factor that activates members of the
      epidermal growth factor family of tyrosine kinase receptors including erbB2 that
      is overexpressed in more aggressive types of breast cancer. The exact role that
      NRG plays in breast cancer is complicated by the fact that NRG has been shown to
      have both proliferative and antiproliferative effects, depending on the breast
      cancer cell line used. Using an isogenic series of breast epithelial cell lines
      (MCF10A) ranging from benign to malignant, we found that the actions of NRG
      changed from antiproliferative to proliferative as the cells progress to cancer.
      This correlated with a progressive inability of NRG to down-regulate a group of
      proliferation genes identified previously using cDNA microarrays. As the cells
      progress to malignancy, they expressed higher levels of erbB2 and lower levels of
      erbB3 and secreted high levels of NRG into the culture media, resulting in high
      basal levels of erbB receptor phosphorylation. Disruption of this autocrine
      signaling loop by blocking ligand-induced receptor activation inhibited cancer
      cell proliferation. These results demonstrate that the transition of MCF10A cells
      from normal to premalignant to malignant correlates with the development of a
      constitutively active autocrine NRG signaling loop that promotes cell
      proliferation and suggest that disrupting this autocrine loop may provide an
      important therapeutic measure to control breast cancer cell growth.

PMID- 15466204
TI  - Persistent c-FLIP(L) expression is necessary and sufficient to maintain
      resistance to tumor necrosis factor-related apoptosis-inducing ligand-mediated
      apoptosis in prostate cancer.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to
      induce apoptosis in a variety of tumorigenic and transformed cell lines but not
      in many normal cells. Hence, TRAIL has the potential to be an ideal cancer
      therapeutic agent with minimal cytotoxicity. FLICE inhibitory protein (c-FLIP) is
      an important regulator of TRAIL-induced apoptosis. Here, we show that persistent
      expression of c-FLIP(Long) [c-FLIP(L)] is inversely correlated with the ability
      of TRAIL to induce apoptosis in prostate cancer cells. In contrast to TRAIL
      sensitive cells, TRAIL-resistant LNCaP and PC3-TR (a TRAIL-resistant
      subpopulation of PC3) cells showed increased c-FLIP(L) mRNA levels and maintained
      steady protein expression of c-FLIP(L) after treatment with TRAIL. Ectopic
      expression of c-FLIP(L) in TRAIL-sensitive PC3 cells changed their phenotype from
      TRAIL sensitive to TRAIL resistant. Conversely, silencing of c-FLIP(L) expression
      by small interfering RNA in PC3-TR cells reversed their phenotype from TRAIL
      resistant to TRAIL sensitive. Therefore, persistent expression of c-FLIP(L) is
      necessary and sufficient to regulate sensitivity to TRAIL-mediated apoptosis in
      prostate cancer cells.

PMID- 15466205
TI  - Suppression of colorectal cancer liver metastasis and extension of survival by
      expression of apolipoprotein(a) kringles.
AB  - The formation of hepatic metastases in colorectal cancer is the main cause of
      patient death. Current therapies directed at hepatic metastasis of colorectal
      cancer have had minimal impact on outcome. Therefore, alternative treatment
      strategies for liver metastasis require development. The present study was
      performed to evaluate the application of cDNA of LK68 encoding apolipoprotein(a)
      kringles IV-9, IV-10, and V as possible candidates for gene therapy treatment of
      this life-threatening disease. The murine colorectal cancer cell line CT26 was
      transduced ex vivo with LK68 cDNA via retroviral gene transfer, and an
      experimental model of hepatic metastasis was established by injecting LK68
      expressing and control cells into the spleens of BALB/c mice. Expression of LK68
      did not affect the growth characteristics and viability of transduced CT26 cells
      in vitro. LK68 produced from CT26 cells substantially inhibited the migration of
      endothelial cells in vitro. In vivo, substantial suppression of liver metastasis
      and prolonged survival were observed in mice bearing LK68-expressing CT26 cells,
      compared with controls. LK68-expressing liver metastases were restricted to
      smaller sizes and displayed decreased microvessel density and increased tumor
      cell apoptosis. Our data collectively indicate that LK68 suppresses angiogenesis
      dependent progression of prevascular micrometastases to macroscopic tumors and
      their growth, which are clinically accessible and biologically relevant
      therapeutic targets. We propose that antiangiogenic gene therapy with LK68 is a
      promising strategy for the treatment of colorectal cancer liver metastasis.

PMID- 15466206
TI  - BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the
      RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression
      and angiogenesis.
AB  - The RAS/RAF signaling pathway is an important mediator of tumor cell
      proliferation and angiogenesis. The novel bi-aryl urea BAY 43-9006 is a potent
      inhibitor of Raf-1, a member of the RAF/MEK/ERK signaling pathway. Additional
      characterization showed that BAY 43-9006 suppresses both wild-type and V599E
      mutant BRAF activity in vitro. In addition, BAY 43-9006 demonstrated significant
      activity against several receptor tyrosine kinases involved in neovascularization
      and tumor progression, including vascular endothelial growth factor receptor
      (VEGFR)-2, VEGFR-3, platelet-derived growth factor receptor beta, Flt-3, and c
      KIT. In cellular mechanistic assays, BAY 43-9006 demonstrated inhibition of the
      mitogen-activated protein kinase pathway in colon, pancreatic, and breast tumor
      cell lines expressing mutant KRAS or wild-type or mutant BRAF, whereas non-small
      cell lung cancer cell lines expressing mutant KRAS were insensitive to inhibition
      of the mitogen-activated protein kinase pathway by BAY 43-9006. Potent inhibition
      of VEGFR-2, platelet-derived growth factor receptor beta, and VEGFR-3 cellular
      receptor autophosphorylation was also observed for BAY 43-9006. Once daily oral
      dosing of BAY 43-9006 demonstrated broad-spectrum antitumor activity in colon,
      breast, and non-small-cell lung cancer xenograft models. Immunohistochemistry
      demonstrated a close association between inhibition of tumor growth and
      inhibition of the extracellular signal-regulated kinases (ERKs) 1/2
      phosphorylation in two of three xenograft models examined, consistent with
      inhibition of the RAF/MEK/ERK pathway in some but not all models. Additional
      analyses of microvessel density and microvessel area in the same tumor sections
      using antimurine CD31 antibodies demonstrated significant inhibition of
      neovascularization in all three of the xenograft models. These data demonstrate
      that BAY 43-9006 is a novel dual action RAF kinase and VEGFR inhibitor that
      targets tumor cell proliferation and tumor angiogenesis.

PMID- 15466207
TI  - Cdc7 inhibition reveals a p53-dependent replication checkpoint that is defective
      in cancer cells.
AB  - Cdc7 is an evolutionarily conserved kinase that regulates S phase by promoting
      replication origin activation. Down-regulation of Cdc7 by small interfering RNA
      in a variety of tumor cell lines causes an abortive S phase, leading to cell
      death by either p53-independent apoptosis or aberrant mitosis. Unlike replication
      fork blockade, Cdc7-depleted tumor cells do not elicit a robust checkpoint
      response; thus, inhibitory signals preventing additional cell cycle progression
      are not generated. In normal fibroblasts, however, a p53-dependent pathway
      actively prevents progression through a lethal S phase in the absence of
      sufficient Cdc7 kinase. We show that in this experimental system, p53 is required
      for the lasting maintenance of this checkpoint and for cell viability. With this
      work we reveal and begin to characterize a novel mechanism that regulates DNA
      synthesis in human cells, and we suggest that inhibition of Cdc7 kinase
      represents a promising approach for the development of a new generation of
      anticancer agents.

PMID- 15466208
TI  - Inhibition of the Raf-MEK1/2-ERK1/2 signaling pathway, Bcl-xL down-regulation,
      and chemosensitization of non-Hodgkin's lymphoma B cells by Rituximab.
AB  - Rituximab (Rituxan, IDEC-C2B8) has been shown to sensitize non-Hodgkin's lymphoma
      (NHL) cell lines to chemotherapeutic drug-induced apoptosis. Rituximab treatment
      of Bcl-2-deficient Ramos cells and Bcl-2-expressing Daudi cells selectively
      decreases Bcl-(xL) expression and sensitizes the cells to paclitaxel-induced
      apoptosis. This study delineates the signaling pathway involved in rituximab
      mediated Bcl-(xL) down-regulation in Ramos and Daudi NHL B cells. We hypothesized
      that rituximab may interfere with the extracellular signal-regulated kinase (ERK)
      1/2 pathway, leading to decreased Bcl-(xL) expression. Rituximab (20 microg/mL)
      inhibited the kinase activity of mitogen-activated protein kinase kinase (MEK)
      1/2 and reduced the phosphorylation of the components of the ERK1/2 pathway (Raf
      1, MEK1/2, and ERK1/2) and decreased activator protein-1 DNA binding activity and
      Bcl-(xL) gene expression. These events occurred with similar kinetics and were
      observed 3 to 6 hours after rituximab treatment. Rituximab-mediated effects were
      corroborated by using specific inhibitors of the ERK1/2 pathway, which also
      reduced Bcl-(xL) levels and sensitized the NHL B cells to paclitaxel-induced
      apoptosis. Previous findings implicated a negative regulatory role of the Raf-1
      kinase inhibitor protein (RKIP) on the ERK1/2 pathway. Rituximab treatment of NHL
      B cells significantly up-regulated RKIP expression, thus interrupting the ERK1/2
      signaling pathway through the physical association between Raf-1 and RKIP, which
      was concomitant with Bcl-(xL) down-regulation. These novel findings reveal a
      signaling pathway triggered by rituximab, whereby rituximab-mediated up
      regulation of RKIP adversely regulates the activity of the ERK1/2 pathway, Bcl
      (xL) expression, and subsequent chemosensitization of drug-refractory NHL B
      cells. The significance of these findings is discussed.

PMID- 15466209
TI  - Antitumor effect of a novel proapoptotic peptide that impairs the phosphorylation
      by the protein kinase 2 (casein kinase 2).
AB  - Protein Kinase (casein kinase 2, CK2) is a serine-threonine kinase that is
      frequently dysregulated in many human tumors. Therefore we hypothesized that
      peptides capable of binding to the CK2 acidic domain may exhibit potential
      anticancer properties. By screening a random cyclic peptide phage display
      library, we have identified a novel peptide, P15, that abrogated CK2
      phosphorylation by blocking the substrate in vitro. To verify its potential
      antineoplastic effect, P15 was fused to the cell-penetrating peptide derived from
      the HIV-Tat protein. Interestingly, P15-Tat induced apoptosis as evidenced by
      rapid caspase activation and cellular cytotoxicity in a variety of tumor cell
      lines. Furthermore, direct injection of P15-Tat into C57BL6 mice bearing day 7
      established solid tumors, resulted in substantial regression of the tumor mass.
      Our findings describe a new proapoptotic cyclic peptide that blocks the CK2
      phosphorylation and exhibits antitumor effect in vivo, indicating that the P15
      peptide may potentially be used clinically to treat solid tumors or as an
      adjuvant for cancer therapy.

PMID- 15466210
TI  - Celastraceae sesquiterpenes as a new class of modulators that bind specifically
      to human P-glycoprotein and reverse cellular multidrug resistance.
AB  - Overexpression of ABCB1 (MDR1) P-glycoprotein, a multidrug efflux pump, is one
      mechanism by which tumor cells may develop multidrug resistance (MDR), preventing
      the successful chemotherapeutic treatment of cancer. Sesquiterpenes from
      Celastraceae family are natural compounds shown previously to reverse MDR in
      several human cancer cell lines and Leishmania strains. However, their molecular
      mechanism of reversion has not been characterized. In the present work, we have
      studied the ability of 28 dihydro-beta-agarofuran sesquiterpenes to reverse the P
      glycoprotein-dependent MDR phenotype and elucidated their molecular mechanism of
      action. Cytotoxicity assays using human MDR1-transfected NIH-3T3 cells allowed us
      to select the most potent sesquiterpenes reversing the in vitro resistance to
      daunomycin and vinblastine. Flow cytometry experiments showed that the above
      active compounds specifically inhibited drug transport activity of P-glycoprotein
      in a saturable, concentration-dependent manner (K(i) down to 0.24 +/- 0.01
      micromol/L) but not that of ABCC1 (multidrug resistance protein 1; MRP1), ABCC2
      (MRP2), and ABCG2 (breast cancer resistance protein; BCRP) transporters.
      Moreover, sesquiterpenes inhibited at submicromolar concentrations the P
      glycoprotein-mediated transport of [(3)H]colchicine and tetramethylrosamine in
      plasma membrane from CH(R)B30 cells and P-glycoprotein-enriched proteoliposomes,
      supporting that P-glycoprotein is their molecular target. Photoaffinity labeling
      in plasma membrane and fluorescence spectroscopy experiments with purified
      protein suggested that sesquiterpenes interact with transmembrane domains of P
      glycoprotein. Finally, sesquiterpenes modulated P-glycoprotein ATPase-activity in
      a biphasic, concentration-dependent manner: they stimulated at very low
      concentrations but inhibited ATPase activity as noncompetitive inhibitors at
      higher concentrations. Sesquiterpenes from Celastraceae are promising P
      glycoprotein modulators with potential applications in cancer chemotherapy
      because of their MDR reversal potency and specificity for P-glycoprotein.

PMID- 15466211
TI  - ATR affecting cell radiosensitivity is dependent on homologous recombination
      repair but independent of nonhomologous end joining.
AB  - ATR is one of the most important checkpoint proteins in mammalian cells
      responding to DNA damage. Cells defective in normal ATR activity are sensitive to
      ionizing radiation (IR). The mechanism by which ATR protects the cells from IR
      induced killing remains unclear. DNA double-strand breaks (DSBs) induced by IR
      are critical lesions for cell survival. Two major DNA DSB repair pathways exist
      in mammalian cells: homologous recombination repair (HRR) and nonhomologous end
      joining (NHEJ). We show that the doxycycline (dox)-induced ATR kinase dead
      (ATRkd) cells have the similar inductions and rejoining rates of DNA DSBs
      compared with cells without dox induction, although the dox-induced ATRkd cells
      are more sensitive to IR and have the deficient S and G(2) checkpoints. We also
      show that the dox-induced ATRkd cells have a lower HRR efficiency compared with
      the cells without dox induction. These results indicate that the effects of ATR
      on cell radiosensitivity are independent of NHEJ but are linked to HRR that may
      be affected by the deficient S and G(2) checkpoints.

PMID- 15466212
TI  - Radiation sensitivity, H2AX phosphorylation, and kinetics of repair of DNA strand
      breaks in irradiated cervical cancer cell lines.
AB  - Six human cervical cancer cell lines [five human papillomavirus (HPV) positive,
      one HPV negative] for induction and rejoining of DNA strand breaks and for
      kinetics of formation and loss of serine 139 phosphorylated histone H2AX
      (gammaH2AX). X-rays induced the same level of DNA breakage for all cell lines. By
      8 hours after 20 Gy, <2% of the initial single-strand breaks remained and no
      double-strand breaks could be detected. In contrast, 24 hours after irradiation,
      gammaH2AX representing up to 30% of the initial signal still present. SW756 cells
      showed almost four times higher background levels of gammaH2AX and no residual
      gammaH2AX compared with the most radiosensitive HPV-negative C33A cells that
      showed the lowest background and retained 30% of the maximum level of gammaH2AX.
      Radiation sensitivity, measured as clonogenic-surviving fraction after 2 Gy, was
      correlated with the fraction of gammaH2AX remaining 24 hours after irradiation. A
      substantial correlation with gammaH2AX loss half-time measured over the first 4
      hours was seen only when cervical cell lines were included in a larger series of
      p53-deficient cell lines. Interestingly, p53 wild-type cell lines consistently
      showed faster gammaH2AX loss half-times than p53-deficient cell lines. We
      conclude that cell line-dependent differences in loss of gammaH2AX after
      irradiation are related in part to intrinsic radiosensitivity. The possibility
      that the presence of gammaH2AX foci may not always signify the presence of a
      physical break, notably in some tumor cell lines, is also supported by these
      results.

PMID- 15466213
TI  - Crucial role for interferon gamma in the synergism between tumor vasculature
      targeted tumor necrosis factor alpha (NGR-TNF) and doxorubicin.
AB  - NGR-TNF is a derivative of TNF-alpha, consisting of TNF fused to CNGRCG, a tumor
      vasculature-targeting peptide. Previous studies showed that NGR-TNF can exert
      synergistic antitumor effects with doxorubicin and with other chemotherapeutic
      drugs in murine models. In this study, we have investigated the role of
      endogenous IFN-gamma on the antitumor activity of NGR-TNF in combination with
      doxorubicin. The study was carried out using murine B16F1 melanoma and TS/A
      mammary adenocarcinoma implanted subcutaneously in (a) immunocompetent mice, (b)
      athymic nude mice, and (c) IFN-gamma-knockout mice. Synergism between NGR-TNF and
      doxorubicin was observed in immunocompetent mice but not in nude or IFN-gamma
      knockout mice. Preadministration of a neutralizing anti-IFN-gamma antibody to
      immunocompetent mice inhibited the NGR-TNF/doxorubicin synergism, whereas
      administration of IFN-gamma to nude and to IFN-gamma-knockout mice restored the
      synergistic activity. The synergism in nude mice was restored also by
      transfecting tumor cells with the IFN-gamma cDNA. Administration of NGR-TNF in
      combination with IFN-gamma to nude mice, but not of NGR-TNF alone, doubled the
      penetration of doxorubicin in TS/A tumors. These findings point to a crucial role
      for locally produced IFN-gamma in tumor vascular targeting with NGR-TNF and
      doxorubicin. Finally, addition of IFN-gamma to the treatment of immunocompetent
      mice with NGR-TNF/doxorubicin induced only modest improvement in response,
      suggesting that exogenous IFN-gamma can improve the therapeutic activity of these
      drugs only in case of suboptimal production of endogenous IFN-gamma.

PMID- 15466214
TI  - Changes in androgen receptor nongenotropic signaling correlate with transition of
      LNCaP cells to androgen independence.
AB  - A cure for prostate cancer (CaP) will be possible only after a complete
      understanding of the mechanisms causing this disease to progress from androgen
      dependence to androgen independence. To carry on a careful characterization of
      the phenotypes of CaP cell lines before and after acquisition of androgen
      independence, we used two human CaP LNCaP sublines: LNCaP(nan), which is androgen
      dependent (AD), and LNCaP-HP, which is androgen independent (AI). In AD
      LNCaP(nan) cells, dihydrotestosterone (DHT) stimulated in an androgen receptor
      (AR)-dependent way a phosphorylation signaling pathway involving steroid receptor
      coactivator (Src)-mitogen-activated protein/extracellular signal-regulated kinase
      (ERK) kinase (MEK)-1/2-ERK-1/2-cAMP-response element binding-protein (CREB).
      Activation of this pathway was associated with increased [(3)H]thymidine
      incorporation and resistance to apoptosis. Use of dominant-negative forms of MEK
      1/2 and CREB demonstrated in LNCaP(nan) cells that DHT induced [(3)H]thymidiine
      incorporation through a thus far unidentified molecule activated downstream of
      MEK-1/2, and antiapoptosis through phosphorylation of the transcription factor
      CREB. In contrast, in AI LNCaP-HP cells, the Src-MEK-1/2-ERK-1/2-CREB pathway was
      constitutively active. Because it was not further stimulated by addition of DHT,
      no increase of [(3)H]thymidine incorporation or apoptosis resistance was
      demonstrated in LNCaP-HP cells. Additional experiments showed that Src and the
      scaffold protein MNAR coimmunoprecipitated with AR, indicating a role for Src as
      an apical molecule in the Src-MEK-1/2-ERK-1/2-CREB pathway. Interestingly,
      differences between the two cell lines were that in LNCaP-HP cells presence of an
      AI phenotype and lack of response to DHT were associated with constitutive
      activation of the protein kinase Src and interaction among Src, AR, and MNAR. In
      contrast, in LNCaP(nan) cells, presence of an AD phenotype and ability to respond
      to DHT were associated with DHT-dependent activation of Src kinase activity and
      interaction among Src, AR, and MNAR. Intriguingly, in LNCaP(nan) cells, we found
      that transcription through the prototypical CREB-responsive promoter c-fos could
      be induced in a DHT-dependent way, and this action was inhibited by the AR
      antagonist Casodex and MEK-1 inhibitor PD98059. In contrast, transcription
      through the PSA P/E promoter, a prototypical AR-dependent promoter directly
      activated by agonist, was obliterated only by Casodex. Additional experiments
      with genital skin fibroblasts derived from patients with a variety of AR
      abnormalities indicated that nongenotropic AR signaling does not depend on an
      intact DNA-binding domain or on the ability of AR to translocate to the nucleus.
      The results suggest the following: (1) Constitutive activation of the Src-MEK-1/2
      ERK-1/2-CREB pathway is associated with the AI phenotype observed in LNCaP-HP
      cells. (2) Activation of the Src-MEK-1/2-ERK-1/2-CREB pathway is DHT dependent in
      AD LNCaP(nan) cells. (3) DHT activation of this pathway is associated with
      induction of [(3)H]thymidine incorporation by a molecule activated downstream of
      MEK-1/2 and of antiapoptosis through activation of the transcription factor CREB
      in AD LNCaP(nan) cells. (4) AR regulates transcription either directly upon
      ligand binding and nuclear translocation or indirectly through kinase pathways
      leading to activation of downstream transcription factors. (5) Nuclear
      translocation and ability of the DNA-binding domain of AR to interact with DNA
      are not prerequisites for nongenotropic AR activity.

PMID- 15466215
TI  - Haploid inactivation of the amplified-in-breast cancer 3 coactivator reduces the
      inhibitory effect of peroxisome proliferator-activated receptor gamma and
      retinoid X receptor on cell proliferation and accelerates polyoma middle-T
      antigen-induced mammary tumorigenesis in mice.
AB  - The amplified-in-breast cancer 3 (AIB3) is a nuclear receptor coactivator
      amplified and overexpressed in human breast cancers. AIB3(-/-) mice die during
      gestation, whereas AIB3(+/-) mice exhibit normal development. Here, we
      demonstrate that AIB3 protein is mainly located in the nuclei of mammary
      epithelial cells and tumor cells and its levels are elevated in mammary
      epithelial cells at middle pregnant stage and in mammary tumor cells. To examine
      whether AIB3 reduction affects mammary tumorigenesis, we generated wild-type
      mouse mammary tumor virus/polyoma middle-T (WT/PyMT) and AIB3(+/-)/PyMT mice.
      Mammary tumor development in AIB3(+/-)/PyMT female and male mice was
      substantially accelerated compared with that in WT/PyMT mice, because of
      increased cell proliferation in early tumorigenic lesions, including ductal
      hyperplasia and mammary intraepithelial neoplasia. Tumor formation in nude mice
      that received premalignant AIB3(+/-)/PyMT mammary tissue was much faster than in
      nude mice that received transplants of premalignant WT/PyMT mammary tissue, which
      indicated that the accelerated tumorigenesis in AIB3(+/-)/PyMT mammary glands is
      due to a mammary epithelial autonomous defect. Expression of PyMT, estrogen
      receptor alpha and estrogen receptor alpha-regulated genes was unaffected in
      AIB3(+/-)/PyMT mammary glands, which suggests that the acceleration of mammary
      tumor formation in AIB3(+/-)/PyMT mice was not a consequence of changes in PyMT
      expression or in estrogen receptor function. Importantly, the inhibitory effects
      of peroxisome proliferator-activated receptor gamma (PPARgamma) and retinoid-X
      receptor (RXR) ligands on AIB3(+/-)/PyMT cell proliferation and the
      transcriptional function of PPARgamma in AIB3(+/-)/PyMT cells were reduced. Thus,
      AIB3 haplodeficiency may facilitate PyMT-induced tumorigenesis through a partial
      impairment of PPARgamma and RXR function. These results suggest that AIB3 may be
      a tumor suppressor that is required for the inhibition of cell proliferation by
      PPARgamma and RXR.

PMID- 15466216
TI  - Symposium on androgen action in prostate cancer.

PMID- 15466217
TI  - Quantification of compartmented metabolic fluxes in developing soybean embryos by
      employing biosynthetically directed fractional (13)C labeling, two-dimensional
      [(13)C, (1)H] nuclear magnetic resonance, and comprehensive isotopomer balancing.
AB  - Metabolic flux quantification in plants is instrumental in the detailed
      understanding of metabolism but is difficult to perform on a systemic level.
      Toward this aim, we report the development and application of a computer-aided
      metabolic flux analysis tool that enables the concurrent evaluation of fluxes in
      several primary metabolic pathways. Labeling experiments were performed by
      feeding a mixture of U-(13)C Suc, naturally abundant Suc, and Gln to developing
      soybean (Glycine max) embryos. Two-dimensional [(13)C, (1)H] NMR spectra of seed
      storage protein and starch hydrolysates were acquired and yielded a labeling data
      set consisting of 155 (13)C isotopomer abundances. We developed a computer
      program to automatically calculate fluxes from this data. This program accepts a
      user-defined metabolic network model and incorporates recent mathematical
      advances toward accurate and efficient flux evaluation. Fluxes were calculated
      and statistical analysis was performed to obtain sds. A high flux was found
      through the oxidative pentose phosphate pathway (19.99 +/- 4.39 micromol d(-1)
      cotyledon(-1), or 104.2 carbon mol +/- 23.0 carbon mol per 100 carbon mol of Suc
      uptake). Separate transketolase and transaldolase fluxes could be distinguished
      in the plastid and the cytosol, and those in the plastid were found to be at
      least 6-fold higher. The backflux from triose to hexose phosphate was also found
      to be substantial in the plastid (21.72 +/- 5.00 micromol d(-1) cotyledon(-1), or
      113.2 carbon mol +/-26.0 carbon mol per 100 carbon mol of Suc uptake). Forward
      and backward directions of anaplerotic fluxes could be distinguished. The
      glyoxylate shunt flux was found to be negligible. Such a generic flux analysis
      tool can serve as a quantitative tool for metabolic studies and phenotype
      comparisons and can be extended to other plant systems.

PMID- 15466218
TI  - The gravitropism defective 2 mutants of Arabidopsis are deficient in a protein
      implicated in endocytosis in Caenorhabditis elegans.
AB  - The gravitropism defective 2 (grv2) mutants of Arabidopsis show reduced shoot
      phototropism and gravitropism. Amyloplasts in the shoot endodermal cells of grv2
      do not sediment to the same degree as in wild type. The GRV2 gene encodes a 277
      kD polypeptide that is 42% similar to the Caenorhabditis elegans RME-8 protein,
      which is required for endocytosis. We hypothesize that a defect in endocytosis
      may affect both the initial gravity sensing via amyloplasts sedimentation and the
      subsequent more general tropic growth response.

PMID- 15466219
TI  - Short-term growth responses to ethylene in Arabidopsis seedlings are EIN3/EIL1
      independent.
AB  - Kinetic studies indicate there are two phases to growth inhibition by ethylene
      for the hypocotyls of etiolated Arabidopsis seedlings. Phase I is transient,
      while phase II results in sustained growth inhibition. The EIN2 membrane protein
      is required for both the first and second phases of growth inhibition by
      ethylene, while the transcription factors EIN3 and EIL1 are required for the
      second phase but not the first phase. The first phase lasts no more than 2 h. It
      is less sensitive to the ethylene response inhibitor 1-methylcyclopropene and
      more sensitive to ethylene than the second phase. The first phase shows
      adaptation at low concentrations of ethylene (< or =0.01 microL L(-1)) with a
      relative refractory period of 5 h after ethylene is added. A modified signal
      transduction model is proposed that accounts for the two phases of growth
      inhibition.

PMID- 15466220
TI  - Arabidopsis seedling growth response and recovery to ethylene. A kinetic
      analysis.
AB  - Responses to the plant hormone ethylene are mediated by a family of five
      receptors in Arabidopsis that act in the absence of ethylene as negative
      regulators of response pathways. In this study, we examined the rapid kinetics of
      growth inhibition by ethylene and growth recovery after ethylene withdrawal in
      hypocotyls of etiolated seedlings of wild-type and ethylene receptor-deficient
      Arabidopsis lines. This analysis revealed that there are two phases to growth
      inhibition by ethylene in wild type: a rapid phase followed by a prolonged,
      slower phase. Full recovery of growth occurs approximately 90 min after ethylene
      removal. None of the receptor null mutations tested had a measurable effect on
      the two phases of growth inhibition. However, loss-of-function mutations in ETR1,
      ETR2, and EIN4 significantly prolonged the time for recovery of growth rate after
      ethylene was removed. Plants with an etr1-6;etr2-3;ein4-4 triple loss-of-function
      mutation took longer to recover than any of the single mutants, while the
      ers1;ers2 double mutant had no effect on recovery rate, suggesting that receiver
      domains play a role in recovery. Transformation of the ers1-2;etr1-7 double
      mutant with wild-type genomic ETR1 rescued the slow recovery phenotype, while a
      His kinase-inactivated ETR1 construct did not. To account for the rapid recovery
      from growth inhibition, a model in which clustered receptors act cooperatively is
      proposed.

PMID- 15466221
TI  - Unique and overlapping expression patterns among the Arabidopsis 1-amino
      cyclopropane-1-carboxylate synthase gene family members.
AB  - 1-Aminocyclopropane-1-carboxylate synthase (ACS) catalyzes the rate-limiting step
      in the ethylene biosynthetic pathway in plants. The Arabidopsis genome encodes
      nine ACS polypeptides that form eight functional (ACS2, ACS4-9, and ACS11)
      homodimers and one nonfunctional (ACS1) homodimer. Transgenic Arabidopsis lines
      were constructed expressing the beta-glucuronidase (GUS) and green fluorescence
      protein (GFP) reporter genes from the promoter of each of the gene family members
      to determine their patterns of expression during plant development. All genes,
      except ACS9, are expressed in 5-d-old etiolated or light-grown seedlings yielding
      distinct patterns of GUS staining. ACS9 expression is detected later in
      development. Unique and overlapping expression patterns were detected for all the
      family members in various organs of adult plants. ACS11 is uniquely expressed in
      the trichomes of sepals and ACS1 in the replum. Overlapping expression was
      observed in hypocotyl, roots, various parts of the flower (sepals, pedicle,
      style, etc.) and in the stigmatic and abscission zones of the silique. Exogenous
      indole-3-acetic acid (IAA) enhances the constitutive expression of ACS2, 4, 5, 6,
      7, 8, and 11 in the root. Wounding of hypocotyl tissue inhibits the constitutive
      expression of ACS1 and ACS5 and induces the expression of ACS2, 4, 6, 7, 8, and
      11. Inducers of ethylene production such as cold, heat, anaerobiosis, and Li(+)
      ions enhance or suppress the expression of various members of the gene family in
      the root of light-grown seedlings. Examination of GUS expression in transverse
      sections of cotyledons reveals that all ACS genes, except ACS9, are expressed in
      the epidermis cell layer, guard cells, and vascular tissue. Similar analysis with
      root tip tissue treated with IAA reveals unique and overlapping expression
      patterns in the various cell types of the lateral root cap, cell division, and
      cell expansion zones. IAA inducibility is gene-specific and cell type-dependent
      across the root tip zone. This limited comparative exploration of ACS gene family
      expression reveals constitutive spatial and temporal expression patterns of all
      gene family members throughout the growth period examined. The unique and
      overlapping gene activity pattern detected reveals a combinatorial code of spatio
      temporal coexpression among the various gene family members during plant
      development. This raises the prospect that functional ACS heterodimers may be
      formed in planta.

PMID- 15466222
TI  - Genetic control of storage oil synthesis in seeds of Arabidopsis.
AB  - Quantitative trait loci (QTL) that control seed oil content and fatty acid
      composition were studied using a recombinant inbred population derived from a
      cross between the Arabidopsis ecotypes Landsberg erecta and Cape Verdi Islands.
      Multiple QTL model mapping identified two major and two minor QTL that account
      for 43% of the variation in oil content in the population. The most significant
      QTL is at the bottom of chromosome 2 and accounts for 17% of the genetic
      variation. Two other significant QTL, located on the upper and lower arms of
      chromosome 1, account for a further 19% of the genetic variation. A QTL near to
      the top of chomosome 3 is epistatic to that on the upper arm of chromosome 1.
      There are strong QTL for linoleic (18:2) and linolenic (18:3) acids contents that
      colocate with the FAD3 locus, another for oleic acid (18:1) that colocates with
      FAD2 and other less significant QTL for palmitic (16:0), stearic (18:0), and
      eicosaenoic (20:1) acids. The presence of the QTL for seed oil content on
      chromosome 2 was confirmed by the generation of lines that contain a 22-cM region
      of Landsberg erecta DNA at the bottom of chromosome 2 in a background containing
      Cape Verdi Islands in other regions of the genome that had been shown to
      influence oil content in the QTL analysis.

PMID- 15466223
TI  - The roles of ethylene, auxin, abscisic acid, and gibberellin in the hyponastic
      growth of submerged Rumex palustris petioles.
AB  - Rumex palustris responds to complete submergence with upward movement of the
      younger petioles. This so-called hyponastic response, in combination with
      stimulated petiole elongation, brings the leaf blade above the water surface and
      restores contact with the atmosphere. We made a detailed study of this
      differential growth process, encompassing the complete range of the known signal
      transduction pathway: from the cellular localization of differential growth, to
      the hormonal regulation, and the possible involvement of a cell wall loosening
      protein (expansin) as a downstream target. We show that hyponastic growth is
      caused by differential cell elongation across the petiole base, with cells on the
      abaxial (lower) surface elongating faster than cells on the adaxial (upper)
      surface. Pharmacological studies and endogenous hormone measurements revealed
      that ethylene, auxin, abscisic acid (ABA), and gibberellin regulate different and
      sometimes overlapping stages of hyponastic growth. Initiation of hyponastic
      growth and (maintenance of) the maximum petiole angle are regulated by ethylene,
      ABA, and auxin, whereas the speed of the response is influenced by ethylene, ABA,
      and gibberellin. We found that a submergence-induced differential redistribution
      of endogenous indole-3-acetic acid in the petiole base could play a role in
      maintenance of the response, but not in the onset of hyponastic growth. Since
      submergence does not induce a differential expression of expansins across the
      petiole base, it is unlikely that this cell wall loosening protein is the
      downstream target for the hormones that regulate the differential cell elongation
      leading to submergence-induced hyponastic growth in R. palustris.

PMID- 15466224
TI  - Infection-related activation of the cg12 promoter is conserved between
      actinorhizal and legume-rhizobia root nodule symbiosis.
AB  - Two nitrogen-fixing root nodule symbioses between soil bacteria and higher plants
      have been described: the symbiosis between legume and rhizobia and actinorhizal
      symbioses between plants belonging to eight angiosperm families and the
      actinomycete Frankia. We have recently shown that the subtilisin-like Ser
      protease gene cg12 (isolated from the actinorhizal plant Casuarina glauca) is
      specifically expressed during plant cell infection by Frankia. Here we report on
      the study of C. glauca cg12 promoter activity in the transgenic legume Medicago
      truncatula. We found that cg12 promoter activation is associated with plant cell
      infection by Sinorhizobium meliloti. Furthermore, applications of purified Nod
      factors and mycorrhizal inoculation failed to trigger expression of the cg12
      reporter gene construct. This indicates that at least part of the transcriptional
      environment in plant cells infected by endosymbiotic nitrogen-fixing bacteria is
      conserved between legume and actinorhizal plants. These results are discussed in
      view of recent data concerning molecular phylogeny that suggest a common
      evolutionary origin of all plants entering nitrogen-fixing root nodule symbioses.

PMID- 15466225
TI  - Carbon status constrains light acclimation in the cyanobacterium Synechococcus
      elongatus.
AB  - Acclimation to one environmental factor may constrain acclimation to another.
      Synechococcus elongatus (sp. PCC7942), growing under continuous light in high
      inorganic carbon (Ci; approximately 4 mm) and low-Ci (approximately 0.02 mm)
      media, achieve similar photosynthetic and growth rates under continuous low or
      high light. During acclimation from low to high light, however, high-Ci cells
      exploit the light increase by accelerating their growth rate, while low-Ci cells
      maintain the prelight shift growth rate for many hours, despite increased
      photosynthesis under the higher light. Under increased light, high-Ci cells
      reorganize their photosynthetic apparatus by shrinking the PSII pool and
      increasing Rubisco pool size, thus decreasing the photosynthetic source-to-sink
      ratio. Low-Ci cells also decrease their reductant source-to-sink ratio to a
      similar level as the high-Ci cells, but do so only by increasing their Rubisco
      pool. Low-Ci cells thus invest more photosynthetic reductant into maintaining
      their larger photosystem pool and increasing their Rubisco pool at the expense of
      population growth than do high-Ci cells. In nature, light varies widely over
      minutes to hours and is ultimately limited by daylength. Photosynthetic
      acclimation in S. elongatus occurs in both high and low Ci, but low-Ci cells
      require more time to achieve acclimation. Cells that can tolerate low Ci do so at
      the expense of slower photosynthetic acclimation. Such differences in rates of
      acclimation relative to rates of change in environmental parameters are important
      for predicting community productivity under variable environments.

PMID- 15466226
TI  - Activation of photosynthesis and resistance to photoinhibition in cyanobacteria
      within biological desert crust.
AB  - Filamentous cyanobacteria are the main primary producers in biological desert
      sand crusts. The cells are exposed to extreme environmental conditions including
      temperature, light, and diurnal desiccation/rehydration cycles. We have studied
      the kinetics of activation of photosynthesis during rehydration of the
      cyanobacteria, primarily Microcoleus sp., within crust samples collected in the
      Negev desert, Israel. We also investigated their susceptibility to
      photoinhibition. Activation of the photosynthetic apparatus, measured by
      fluorescence kinetics, thermoluminescence, and low temperature fluorescence
      emission spectra, did not require de novo protein synthesis. Over 50% of the
      photosystem II (PSII) activity, assembled phycobilisomes, and photosystem I (PSI)
      antennae were detected within less than 5 min of rehydration. Energy transfer to
      PSII and PSI by the respective antennae was fully established within 10 to 20 min
      of rehydration. The activation of a fraction of PSII population (about 20%-30%)
      was light and temperature-dependent but did not require electron flow to
      plastoquinone [was not inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea]. The
      cyanobacteria within the crusts are remarkably resistant to photoinhibition even
      in the absence of protein synthesis. The rate of PSII repair increased with light
      intensity and with time of exposure. Consequently, the extent of photoinhibition
      in high-light-exposed crusts reached a constant, relatively low, level. This is
      in contrast to model organisms such as Synechocystis sp. strain PCC 6803 where
      PSII activity declined continuously over the entire exposure to high
      illumination. Ability of the crust's organisms to rapidly activate photosynthesis
      upon rehydration and withstand photoinhibition under high light intensity may
      partly explain their ability to survive in this ecosystem.

PMID- 15466227
TI  - Cloning and characterization of red clover polyphenol oxidase cDNAs and
      expression of active protein in Escherichia coli and transgenic alfalfa.
AB  - Red clover (Trifolium pratense) leaves contain high levels of polyphenol oxidase
      (PPO) activity and o-diphenol substrates. Wounding of leaves during harvest and
      ensiling results in browning of leaf tissues from activity of PPO on the o
      diphenols. In association with browning, leaf proteins remain undegraded during
      ensiling, presumably due to PPO-generated o-quinone inhibition of leaf proteases.
      We cloned three red clover PPO cDNAs, PPO1, PPO2, and PPO3, from a leaf cDNA
      library. Sequence comparisons among the three red clover PPO clones indicated
      they are 87% to 90% identical at the nucleotide level (80%-83% amino acid
      identity). All three encode proteins predicted to localize to the chloroplast
      thylakoid lumen. RNA-blotting and immunoblotting experiments indicated PPO1 is
      expressed primarily in young leaves, PPO2 in flowers and petioles, and PPO3 in
      leaves and possibly flowers. We expressed mature PPO1 in Escherichia coli. A
      portion of the expressed protein was soluble and functional in an assay for PPO
      activity. We also expressed the red clover PPO cDNAs under the control of a
      constitutive promoter in alfalfa (Medicago sativa). The expressed red clover PPO
      proteins were active in alfalfa extracts as evidenced by o-diphenol-dependant
      extract browning and quantitative assays of PPO activity. Proteolysis in leaf
      extracts of alfalfa expressing red clover PPO1 was dramatically reduced in the
      presence of an o-diphenol compared to controls. Transgenic alfalfa expressing red
      clover PPO should prove an excellent model system to further characterize the red
      clover PPO enzymes and PPO-mediated inhibition of postharvest proteolysis in
      forage plants.

PMID- 15466228
TI  - Requirement of the histidine kinase domain for signal transduction by the
      ethylene receptor ETR1.
AB  - In Arabidopsis, ethylene is perceived by a receptor family consisting of five
      members, one of these being ETR1. The N-terminal half of ETR1 functions as a
      signal input domain. The C-terminal region of ETR1, consisting of a His kinase
      domain and a putative receiver domain, is likely to function in signal output.
      The role of the proposed signal output region in ethylene signaling was examined
      in planta. For this purpose, the ability of mutant versions of ETR1 to rescue the
      constitutive ethylene-response phenotype of the etr1-6;etr2-3;ein4-4 triple loss
      of-function mutant line was examined. A truncated version of ETR1 that lacks both
      the His kinase domain and the receiver domain failed to rescue the triple mutant
      phenotype. A truncated ETR1 receptor that lacks only the receiver domain restored
      normal growth to the triple mutant in air, but the transgenic seedlings displayed
      hypersensitivity to low doses of ethylene. A mutation that eliminated His kinase
      activity had a modest effect upon the ability of the receptor to repress ethylene
      responses in air. These results demonstrate that the His kinase domain plays a
      role in the repression of ethylene responses. The potential roles of the receiver
      domain and His kinase activity in ethylene signaling are discussed.

PMID- 15466229
TI  - Isolation and characterization of an Arabidopsis mutant that overaccumulates O
      Acetyl-L-Ser.
AB  - O-Acetyl-l-Ser (OAS) is a positive regulator for the expression of sulfur (S)
      deficiency-inducible genes. In this study, through the isolation and analysis of
      Arabidopsis mutants exhibiting altered expression of S-responsive genes, we
      identified a thiol reductase as a regulator of the OAS levels. Ethyl
      methanesulfonate-mutagenized M2 seeds of transgenic Arabidopsis NOB7 carrying a
      chimeric S-responsive promoter driving the green fluorescent protein gene were
      screened for mutants with altered levels of green fluorescence compared to
      parental NOB7 line. One of the lines exhibited elevated levels of green
      fluorescence and mRNA accumulation of several endogenous S-responsive genes and
      carried a single recessive mutation responsible for the phenotype. OAS
      concentration in the rosette leaves of the mutant was about five times higher
      than that of wild-type plants. Based upon the high OAS levels, the mutant was
      named osh1-1 (OAS high accumulation). The OSH1 locus was mapped to a 30-kb region
      in chromosome V. DNA sequence analysis revealed no base change in this region;
      however, a demethylated C residue was found in the first exon of At5g01580.
      At5g01580 mRNA accumulation was higher in osh1-1 than in wild type, while
      transcript levels of other genes in the mapped region were not significantly
      altered in osh1-1. A line of transgenic plants overexpressing At5g01580 had
      elevated levels of endogenous S-responsive genes. These results suggest that
      elevated expression of At5g01580 is the cause of osh1 phenotype. Based on
      sequence similarity to animal thiol reductases, At5g01580 was tested for and
      exhibited thiol reductase activity. Possible roles of a thiol reductase in OAS
      metabolism are discussed.

PMID- 15466230
TI  - Crosslinking of ribosomal proteins to RNA in maize ribosomes by UV-B and its
      effects on translation.
AB  - Ultraviolet-B (UV-B) photons can cause substantial cellular damage in
      biomolecules, as is well established for DNA. Because RNA has the same absorption
      spectrum for UV as DNA, we have investigated damage to this cellular constituent.
      In maize (Zea mays) leaves, UV-B radiation damages ribosomes by crosslinking
      cytosolic ribosomal proteins S14, L23a, and L32, and chloroplast ribosomal
      protein L29 to RNA. Ribosomal damage accumulated during a day of UV-B exposure
      correlated with a progressive decrease in new protein production; however, de
      novo synthesis of some ribosomal proteins is increased after 6 h of UV-B
      exposure. After 16 h without UV-B, damaged ribosomes were eliminated and
      translation was restored to normal levels. Ribosomal protein S6 and an S6 kinase
      are phosphorylated during UV-B exposure; these modifications are associated with
      selective translation of some ribosomal proteins after ribosome damage in
      mammalian fibroblast cells and may be an adaptation in maize. Neither
      photosynthesis nor pigment levels were affected significantly by UV-B,
      demonstrating that the treatment applied is not lethal and that maize leaf
      physiology readily recovers.

PMID- 15466231
TI  - The central role of PhEIN2 in ethylene responses throughout plant development in
      petunia.
AB  - The plant hormone ethylene regulates many aspects of growth and development. Loss
      of-function mutations in ETHYLENE INSENSITIVE2 (EIN2) result in ethylene
      insensitivity in Arabidopsis, indicating an essential role of EIN2 in ethylene
      signaling. However, little is known about the role of EIN2 in species other than
      Arabidopsis. To gain a better understanding of EIN2, a petunia (Petunia x hybrida
      cv Mitchell Diploid [MD]) homolog of the Arabidopsis EIN2 gene (PhEIN2) was
      isolated, and the role of PhEIN2 was analyzed in a wide range of plant responses
      to ethylene, many that do not occur in Arabidopsis. PhEIN2 mRNA was present at
      varying levels in tissues examined, and the PhEIN2 expression decreased after
      ethylene treatment in petals. These results indicate that expression of PhEIN2
      mRNA is spatially and temporally regulated in petunia during plant development.
      Transgenic petunia plants with reduced PhEIN2 expression were compared to wild
      type MD and ethylene-insensitive petunia plants expressing the Arabidopsis etr1-1
      gene for several physiological processes. Both PhEIN2 and etr1-1 transgenic
      plants exhibited significant delays in flower senescence and fruit ripening,
      inhibited adventitious root and seedling root hair formation, premature death,
      and increased hypocotyl length in seedling ethylene response assays compared to
      MD. Moderate or strong levels of reduction in ethylene sensitivity were achieved
      with expression of both etr1-1 and PhEIN2 transgenes, as measured by downstream
      expression of PhEIL1. These results demonstrate that PhEIN2 mediates ethylene
      signals in a wide range of physiological processes and also indicate the central
      role of EIN2 in ethylene signal transduction.

PMID- 15466232
TI  - Overexpression of constitutive differential growth 1 gene, which encodes a
      RLCKVII-subfamily protein kinase, causes abnormal differential and elongation
      growth after organ differentiation in Arabidopsis.
AB  - To better understand genetic regulation of differential growth of plant organs, a
      dominant and semidwarf mutant, constitutive differential growth 1-Dominant (cdg1
      D), was isolated utilizing the technique of activation tagging. cdg1-D showed
      pleiotropic phenotype including dwarfism, exaggerated leaf epinasty, and twisted
      or spiral growth in hypocotyl, inflorescence stem, and petiole. Hypocotyls of
      cdg1-D were longer than those of wild type under light conditions. The phenotype
      was caused by activation tagging of CDG1 gene that encodes a receptor-like
      cytoplasmic kinase of RLCKVII subfamily. When treated with high concentrations of
      brassinolide, light-grown wild-type seedlings showed long hypocotyls and strong
      leaf epinasty as observed in cdg1-D seedlings. Treatment of cdg1-D with
      brassinazole, a specific inhibitor of brassinosteroid (BR) biosynthesis, did not
      rescue the mutant phenotype. Gene expression of CONSTITUTIVE PHOTOMORPHOGENESIS
      AND DWARFISM involved in BR biosynthesis and phyB ACTIVATION-TAGGED SUPPRESSOR1
      that inactivates BR was repressed and induced, respectively, in cdg1-D plants,
      suggesting constitutive activation of BR signaling in the mutant. CDG1 was
      expressed at a very low level in all the organs of the wild type tested. We
      isolated two independent intragenic suppressors of cdg1-D. However, they showed
      normal morphology and responded to BR in a similar manner to wild type. Taken
      together, CDG1 gene may interfere with signal transduction of BR when
      overexpressed, but is not an essential factor for it in the wild type.

PMID- 15466233
TI  - Uncoupling the effects of abscisic acid on plant growth and water relations.
      Analysis of sto1/nced3, an abscisic acid-deficient but salt stress-tolerant
      mutant in Arabidopsis.
AB  - We have identified a T-DNA insertion mutation of Arabidopsis (ecotype C24), named
      sto1 (salt tolerant), that results in enhanced germination on both ionic (NaCl)
      and nonionic (sorbitol) hyperosmotic media. sto1 plants were more tolerant in
      vitro than wild type to Na(+) and K(+) both for germination and subsequent growth
      but were hypersensitive to Li(+). Postgermination growth of the sto1 plants on
      sorbitol was not improved. Analysis of the amino acid sequence revealed that STO1
      encodes a 9-cis-epoxicarotenoid dioxygenase (similar to 9-cis-epoxicarotenoid
      dioxygenase GB:AAF26356 [Phaseolus vulgaris] and to NCED3 GB:AB020817
      [Arabidopsis]), a key enzyme in the abscisic acid (ABA) biosynthetic pathway.
      STO1 transcript abundance was substantially reduced in mutant plants. Mutant sto1
      plants were unable to accumulate ABA following a hyperosmotic stress, although
      their basal ABA level was only moderately altered. Either complementation of the
      sto1 with the native gene from the wild-type genome or supplementation of ABA to
      the growth medium restored the wild-type phenotype. Improved growth of sto1
      mutant plants on NaCl, but not sorbitol, medium was associated with a reduction
      in both NaCl-induced expression of the ICK1 gene and ethylene accumulation.
      Osmotic adjustment of sto1 plants was substantially reduced compared to wild-type
      plants under conditions where sto1 plants grew faster. The sto1 mutation has
      revealed that reduced ABA can lead to more rapid growth during hyperionic stress
      by a signal pathway that apparently is at least partially independent of signals
      that mediate nonionic osmotic responses.

PMID- 15466234
TI  - Biochemical characterization of the tobacco 42-kD protein kinase activated by
      osmotic stress.
AB  - In tobacco (Nicotiana tabacum), hyperosmotic stress induces rapid activation of a
      42-kD protein kinase, referred to as Nicotiana tabacum osmotic stress-activated
      protein kinase (NtOSAK). cDNA encoding the kinase was cloned and, based on the
      predicted amino acid sequence, the enzyme was assigned to the SNF1-related
      protein kinase type 2 (SnRK2) family. The identity of the enzyme was confirmed by
      immunoprecipitation of the active kinase from tobacco cells subjected to osmotic
      stress using antibodies raised against a peptide corresponding to the C-terminal
      sequence of the kinase predicted from the cloned cDNA. A detailed biochemical
      characterization of NtOSAK purified from stressed tobacco cells was performed.
      Our results show that NtOSAK is a calcium-independent Ser/Thr protein kinase. The
      sequence of putative phosphorylation sites recognized by NtOSAK, predicted by the
      computer program PREDIKIN, resembled the substrate consensus sequence defined for
      animal and yeast (Saccharomyces cerevisiae) AMPK/SNF1 kinases. Our experimental
      data confirmed these results, as various targets for AMPK/SNF1 kinases were also
      efficiently phosphorylated by NtOSAK. A range of protein kinase inhibitors was
      tested as potential modulators of NtOSAK, but only staurosporine, a rather
      nonspecific protein kinase inhibitor, was found to abolish the enzyme activity.
      In phosphorylation reactions, NtOSAK exhibited a preference for Mg(2+) over
      Mn(2+) ions and an inability to use GTP instead of ATP as a phosphate donor. The
      enzyme activity was not modulated by 5'-AMP. To our knowledge, these results
      represent the first detailed biochemical characterization of a kinase of the
      SnRK2 family.

PMID- 15466235
TI  - Patellin1, a novel Sec14-like protein, localizes to the cell plate and binds
      phosphoinositides.
AB  - Membrane trafficking is central to construction of the cell plate during plant
      cytokinesis. Consequently, a detailed understanding of the process depends on the
      characterization of molecules that function in the formation, transport,
      targeting, and fusion of membrane vesicles to the developing plate, as well as
      those that participate in its consolidation and maturation into a fully
      functional partition. Here we report the initial biochemical and functional
      characterization of patellin1 (PATL1), a novel cell-plate-associated protein that
      is related in sequence to proteins involved in membrane trafficking in other
      eukaryotes. Analysis of the Arabidopsis genome indicated that PATL1 is one of a
      small family of Arabidopsis proteins, characterized by a variable N-terminal
      domain followed by two domains found in other membrane-trafficking proteins
      (Sec14 and Golgi dynamics domains). Results from immunolocalization and
      biochemical fractionation studies suggested that PATL1 is recruited from the
      cytoplasm to the expanding and maturing cell plate. In vesicle-binding assays,
      PATL1 bound to specific phosphoinositides, important regulators of membrane
      trafficking, with a preference for phosphatidylinositol(5)P,
      phosphatidylinositol(4,5)P(2), and phosphatidylinositol(3)P. Taken together,
      these findings suggest a role for PATL1 in membrane-trafficking events associated
      with cell-plate expansion or maturation and point to the involvement of
      phosphoinositides in cell-plate biogenesis.

PMID- 15466236
TI  - Production of reactive oxygen intermediates (O(2)(.-), H(2)O(2), and (.)OH) by
      maize roots and their role in wall loosening and elongation growth.
AB  - Cell extension in the growing zone of plant roots typically takes place with a
      maximum local growth rate of 50% length increase per hour. The biochemical
      mechanism of this dramatic growth process is still poorly understood. Here we
      test the hypothesis that the wall-loosening reaction controlling root elongation
      is effected by the production of reactive oxygen intermediates, initiated by a
      NAD(P)H oxidase-catalyzed formation of superoxide radicals (O(2)(.-)) at the
      plasma membrane and culminating in the generation of polysaccharide-cleaving
      hydroxyl radicals ((.)OH) by cell wall peroxidase. The following results were
      obtained using primary roots of maize (Zea mays) seedlings as experimental
      material. (1) Production of O(2)(.-), H(2)O(2), and (.)OH can be demonstrated in
      the growing zone using specific histochemical assays and electron paramagnetic
      resonance spectroscopy. (2) Auxin-induced inhibition of growth is accompanied by
      a reduction of O(2)(.-) production. (3) Experimental generation of (.)OH in the
      cell walls with the Fenton reaction causes wall loosening (cell wall creep),
      specifically in the growing zone. Alternatively, wall loosening can be induced by
      (.)OH produced by endogenous cell wall peroxidase in the presence of NADH and
      H(2)O(2). (4) Inhibition of endogenous (.)OH formation by O(2)(.-) or (.)OH
      scavengers, or inhibitors of NAD(P)H oxidase or peroxidase activity, suppress
      elongation growth. These results show that juvenile root cells transiently
      express the ability to generate (.)OH, and to respond to (.)OH by wall loosening,
      in passing through the growing zone. Moreover, inhibitor studies indicate that
      (.)OH formation is essential for normal root growth.

PMID- 15466237
TI  - Comparative sequence analysis of the region harboring the hardness locus in
      barley and its colinear region in rice.
AB  - The ancestral shared synteny concept has been advocated as an approach to
      positionally clone genes from complex genomes. However, the unified grass genome
      model and the study of grasses as a single syntenic genome is a topic of
      considerable controversy. Hence, more quantitative studies of cereal colinearity
      at the sequence level are required. This study compared a contiguous 300-kb
      sequence of the barley (Hordeum vulgare) genome with the colinear region in rice
      (Oryza sativa). The barley sequence harbors genes involved in endosperm texture,
      which may be the subject of distinctive evolutionary forces and is located at the
      extreme telomeric end of the short arm of chromosome 5H. Comparative sequence
      analysis revealed the presence of five orthologous genes and a complex,
      postspeciation evolutionary history involving small chromosomal rearrangements, a
      translocation, numerous gene duplications, and extensive transposon insertion.
      Discrepancies in gene content and microcolinearity indicate that caution should
      be exercised in the use of rice as a surrogate for map-based cloning of genes
      from large genome cereals such as barley.

PMID- 15466238
TI  - Structure and mutational analysis of a plant mitochondrial nucleoside diphosphate
      kinase. Identification of residues involved in serine phosphorylation and
      oligomerization.
AB  - We report the first crystal structure of a plant (Pisum sativum L. cv Oregon
      sugarpod) mitochondrial nucleoside diphosphate kinase. Similar to other
      eukaryotic nucleoside diphosphate kinases, the plant enzyme is a hexamer; the six
      monomers in the asymmetric unit are arranged as trimers of dimers. Different
      functions of the kinase have been correlated with the oligomeric structure and
      the phosphorylation of Ser residues. We show that the occurrence of Ser
      autophosphorylation depends on enzymatic activity. The mutation of the strictly
      conserved Ser-119 to Ala reduced the Ser phosphorylation to about one-half of
      that observed in wild type with only a modest change of enzyme activity. We also
      show that mutating another strictly conserved Ser, Ser-69, to Ala reduces the
      enzyme activity to 6% and 14% of wild-type using dCDP and dTDP as acceptors,
      respectively. Changes in the oligomerization pattern of the S69A mutant were
      observed by cross-linking experiments. A reduction in trimer formation and a
      change in the dimer interaction could be detected with a concomitant increase of
      tetramers. We conclude that the S69 mutant is involved in the stabilization of
      the oligomeric state of this plant nucleoside diphosphate kinase.

PMID- 15466239
TI  - Expression profiling in Medicago truncatula identifies more than 750 genes
      differentially expressed during nodulation, including many potential regulators
      of the symbiotic program.
AB  - In this study, we describe a large-scale expression-profiling approach to
      identify genes differentially regulated during the symbiotic interaction between
      the model legume Medicago truncatula and the nitrogen-fixing bacterium
      Sinorhizobium meliloti. Macro- and microarrays containing about 6,000 probes were
      generated on the basis of three cDNA libraries dedicated to the study of root
      symbiotic interactions. The experiments performed on wild-type and symbiotic
      mutant material led us to identify a set of 756 genes either up- or down
      regulated at different stages of the nodulation process. Among these, 41 known
      nodulation marker genes were up-regulated as expected, suggesting that we have
      identified hundreds of new nodulation marker genes. We discuss the possible
      involvement of this wide range of genes in various aspects of the symbiotic
      interaction, such as bacterial infection, nodule formation and functioning, and
      defense responses. Importantly, we found at least 13 genes that are good
      candidates to play a role in the regulation of the symbiotic program. This
      represents substantial progress toward a better understanding of this complex
      developmental program.

PMID- 15466240
TI  - Galactinol synthase1. A novel heat shock factor target gene responsible for heat
      induced synthesis of raffinose family oligosaccharides in Arabidopsis.
AB  - Heat shock factors (HSFs) are transcriptional regulators of the heat shock
      response. The major target of HSFs are the genes encoding heat shock proteins
      (HSPs), which are known to have a protective function that counteracts cytotoxic
      effects. To identify other HSF target genes, which may be important determinants
      for the generation of stress tolerance in Arabidopsis, we screened a library
      enriched for genes that are up-regulated in HSF3 (AtHsfA1b)-overexpressing
      transgenic plants (TPs). Galactinol synthase1 (GolS1) is one of the genes that is
      heat-inducible in wild type, but shows constitutive mRNA levels in HSF3 TPs. The
      generation and analysis of TPs containing GolS1-promoter::beta-glucuronidase
      reporter gene constructs showed that, upon heat stress, the expression is
      transcriptionally controlled and occurs in all vegetative tissues. Functional
      consequences of GolS1 expression were investigated by the quantification of
      raffinose, stachyose, and galactinol contents in wild type, HSF3 TPs, and two
      different GolS1 knockout mutants (gols1-1 and gols1-2). This analysis
      demonstrates that (1) raffinose content in leaves increases upon heat stress in
      wild-type but not in the GolS1 mutant plants; and (2) the level of raffinose is
      enhanced and stachyose is present at normal temperature in HSF3 TPs. These data
      provide evidence that GolS1 is a novel HSF target gene, which is responsible for
      heat stress-dependent synthesis of raffinose, a member of the raffinose family
      oligosaccharides. The biological function of this osmoprotective substance and
      the role of HSF-dependent genes in this biochemical pathway are discussed.

PMID- 15466241
TI  - Use of phenylboronic acids to investigate boron function in plants. Possible role
      of boron in transvacuolar cytoplasmic strands and cell-to-wall adhesion.
AB  - The only defined physiological role of boron in plants is as a cross-linking
      molecule involving reversible covalent bonds with cis-diols on either side of
      borate. Boronic acids, which form the same reversible bonds with cis-diols but
      cannot cross-link two molecules, were used to selectively disrupt boron function
      in plants. In cultured tobacco (Nicotiana tabacum cv BY-2) cells, addition of
      boronic acids caused the disruption of cytoplasmic strands and cell-to-cell wall
      detachment. The effect of the boronic acids could be relieved by the addition of
      boron-complexing sugars and was proportional to the boronic acid-binding strength
      of the sugar. Experiments with germinating petunia (Petunia hybrida) pollen and
      boronate-affinity chromatography showed that boronic acids and boron compete for
      the same binding sites. The boronic acids appear to specifically disrupt or
      prevent borate-dependent cross-links important for the structural integrity of
      the cell, including the organization of transvacuolar cytoplasmic strands. Boron
      likely plays a structural role in the plant cytoskeleton. We conclude that
      boronic acids can be used to rapidly and reversibly induce boron deficiency-like
      responses and therefore are useful tools for investigating boron function in
      plants.

PMID- 15466242
TI  - Boron tolerance in barley is mediated by efflux of boron from the roots.
AB  - Many plants are known to reduce the toxic effects of high soil boron (B) by
      reducing uptake of B, but no mechanism for limiting uptake has previously been
      identified. The B-tolerant cultivar of barley (Hordeum vulgare L.), Sahara, was
      shown to be able to maintain root B concentrations up to 50% lower than in the B
      sensitive cultivar, Schooner. This translated into xylem concentrations that were
      approximately 64% lower and leaf concentrations 73% lower in the tolerant
      cultivar. In both cultivars, B accumulation was rapid and reached a steady-state
      concentration in roots within 3 h. In Schooner, this concentration was similar to
      the external medium, whereas in Sahara, the root concentration was maintained at
      a lower concentration. For this to occur, B must be actively extruded from the
      root in Sahara, and this is presumed to be the basis for B tolerance in barley.
      The extrusion mechanism was inhibited by sodium azide but not by treatment at low
      temperature. Several anion channel inhibitors were also effective in limiting
      extrusion, but it was not clear whether they acted directly or via metabolic
      inhibition. The ability of Sahara to maintain lower root B concentrations was
      constitutive and occurred across a wide range of B concentrations. This ability
      was lost at high pH, and both Schooner and Sahara then had similar root B
      concentrations. A predictive model that is consistent with the empirical results
      and explains the tolerance mechanism based on the presence of a borate anion
      efflux transporter in Sahara is presented.

PMID- 15466243
TI  - Evidence for serine/threonine and histidine kinase activity in the tobacco
      ethylene receptor protein NTHK2.
AB  - Ethylene plays important roles in plant growth, development, and stress
      responses. Two ethylene receptors, ETR1 from Arabidopsis and NTHK1 from tobacco
      (Nicotiana tabacum), have been found to have His kinase (HK) activity and Ser/Thr
      kinase activity, respectively, although both show similarity to bacterial two
      component HK. Here, we report the characterization of another ethylene receptor
      homolog gene, NTHK2, from tobacco. This gene also encodes a HK-like protein and
      is induced by dehydration and CaCl(2) but not significantly affected by NaCl and
      abscisic acid treatments. The biochemical properties of the yeast
      (Schizosaccharomyces pombe)-expressed NTHK2 domains were further characterized.
      We found that NTHK2 possessed Ser/Thr kinase activity in the presence of Mn(2+)
      and had HK activity in the presence of Ca(2+). Several lines of evidence
      supported this conclusion, including hydrolytic stability, phosphoamino acid
      analysis, mutation, deletion, and substrate analysis. These properties have
      implications in elucidation of the complexity of the ethylene signal transduction
      pathway and understanding of ethylene functions in plants.

PMID- 15466244
TI  - Role of farnesoid X receptor in the enhancement of canalicular bile acid output
      and excretion of unconjugated bile acids: a mechanism for protection against
      cholic acid-induced liver toxicity.
AB  - Mice lacking the farnesoid X receptor (FXR) involved in the maintenance of
      hepatic bile acid levels are highly sensitive to cholic acid-induced liver
      toxicity. Serum aspartate aminotransferase (AST) activity was elevated 15.7-fold
      after feeding a 0.25% cholic acid diet, whereas only slight increases in serum
      AST (1.7- and 2.5-fold) were observed in wild-type mice fed 0.25 and 1% cholic
      acid diet, respectively. Bile salt export pump mRNA and protein levels were
      increased in wild-type mice fed 1% cholic acid diet (2.1- and 3.0-fold) but were
      decreased in FXR-null mice fed 0.25% cholic acid diet. The bile acid output rate
      was 2.0- and 3.7-fold higher after feeding of 0.25 and 1.0% cholic acid diet in
      wild-type mice, respectively. On the other hand, no significant increase in bile
      acid output rate was observed in FXR-null mice fed 0.25% cholic acid diet in
      contrast to a significant decrease observed in mice fed a 1.0% cholic acid diet
      in spite of the markedly higher levels of hepatic tauro-conjugated bile acids.
      Unconjugated cholic acid was not detected in the bile of wild-type mice fed a
      control diet, but it was readily detected in wild-type mice fed 1% cholic acid
      diet. The ratio of biliary unconjugated cholic acid to total cholic acid
      (unconjugated cholic acid and tauro-conjugated cholic acid) reached 30% under
      conditions of hepatic taurine depletion. These results suggest that the cholic
      acid-induced enhancement of canalicular bile acid output rates and excretion of
      unconjugated bile acids are involved in adaptive responses for prevention of
      cholic acid-induced toxicity.

PMID- 15466245
TI  - Mechanisms of acetaminophen-induced hepatotoxicity: role of oxidative stress and
      mitochondrial permeability transition in freshly isolated mouse hepatocytes.
AB  - Freshly isolated mouse hepatocytes were used to determine the role of
      mitochondrial permeability transition (MPT) in acetaminophen (APAP) toxicity.
      Incubation of APAP (1 mM) with hepatocytes resulted in cell death as indicated by
      increased alanine aminotransferase in the media and propidium iodide
      fluorescence. To separate metabolic events from later events in toxicity,
      hepatocytes were preincubated with APAP for 2 h followed by centrifugation of the
      cells and resuspension of the pellet to remove the drug and reincubating the
      cells in media alone. At 2 h, toxicity was not significantly different between
      control and APAP-incubated cells; however, preincubation with APAP followed by
      reincubation with media alone resulted in a marked increase in toxicity at 3 to 5
      h that was not different from incubation with APAP for the entire time. Inclusion
      of cyclosporine A, trifluoperazine, dithiothreitol (DTT), or N-acetylcysteine
      (NAC) in the reincubation phase prevented hepatocyte toxicity.
      Dichlorofluorescein fluorescence increased during the reincubation phase,
      indicating increased oxidative stress. Tetramethylrhodamine methyl ester
      perchlorate fluorescence decreased during the reincubation phase indicating a
      loss of mitochondrial membrane potential. Inclusion of cyclosporine A, DTT, or
      NAC decreased oxidative stress and loss of mitochondrial membrane potential.
      Confocal microscopy studies with the dye calcein acetoxymethyl ester indicated
      that MPT had also occurred. These data are consistent with a hypothesis where
      APAP-induced cell death occurs by two phases, a metabolic phase and an oxidative
      phase. The metabolic phase occurs with GSH depletion and APAP-protein binding.
      The oxidative phase occurs with increased oxidative stress, loss of mitochondrial
      membrane potential, MPT, and toxicity.

PMID- 15466246
TI  - A newly synthesized poly(ADP-ribose) polymerase inhibitor, DR2313 [2-methyl
      3,5,7,8-tetrahydrothiopyrano[4,3-d]-pyrimidine-4-one]: pharmacological profiles,
      neuroprotective effects, and therapeutic time window in cerebral ischemia in
      rats.
AB  - We investigated the pharmacological profiles of DR2313 [2-methyl-3,5,7,8
      tetrahydrothiopyrano[4,3-d]pyrimidine-4-one], a newly synthesized poly(ADP
      ribose) polymerase (PARP) inhibitor, and its neuroprotective effects on ischemic
      injuries in vitro and in vivo. DR2313 competitively inhibited poly(ADP
      ribosyl)ation in nuclear extracts of rat brain in vitro (K(i) = 0.23 microM).
      Among several NAD(+)-utilizing enzymes, DR2313 was specific for PARP but not
      selective between PARP-1 and PARP-2. DR2313 also showed excellent profiles in
      water solubility and rat brain penetrability. In in vitro models of cerebral
      ischemia, exposure to hydrogen peroxide or glutamate induced cell death with
      overactivation of PARP, and treatment with DR2313 reduced excessive formation of
      poly(ADP-ribose) and cell death. In both permanent and transient focal ischemia
      models in rats, pretreatment with DR2313 (10 mg/kg i.v. bolus and 10 mg/kg/h i.v.
      infusion for 6 h) significantly reduced the cortical infarct volume. To determine
      the therapeutic time window of neuroprotection by DR2313, the effect of post
      treatment was examined in transient focal ischemia model and compared with that
      of a free radical scavenger, MCI-186 (3-methyl-1-phenyl-2-pyrazolone-5-one).
      Pretreatment with MCI-186 (3 mg/kg i.v. bolus and 3 mg/kg/h i.v. infusion for 6
      h) significantly reduced the infarct volume, whereas the post-treatment failed to
      show any effects. In contrast, post-treatment with DR2313 (same regimen) delaying
      for 2 h after ischemia still prevented the progression of infarction. These
      results indicate that DR2313 exerts neuroprotective effects via its potent PARP
      inhibition, even when the treatment is initiated after ischemia. Thus, a PARP
      inhibitor like DR2313 may be more useful in treating acute stroke than a free
      radical scavenger.

PMID- 15466247
TI  - Activation of metabotropic glutamate receptor 1 dimers requires glutamate binding
      in both subunits.
AB  - Group I metabotropic glutamate receptors (mGluRs) form stable, disulfide-linked
      homodimers. Lack of a verifiably monomeric mGluR1 mutant has led to difficulty in
      assessing the role of dimerization in the molecular mechanism of mGluR1
      activation. The related GABA(B) receptor exhibits striking intradimer cross talk
      (ligand binding at one subunit effectively produces G protein activation at the
      other), but it is unclear whether group I mGluRs exhibit analogous cross talk.
      Signaling of heterologously expressed mGluR1 was examined in isolated rat
      sympathetic neurons by measuring glutamate-mediated inhibition of native calcium
      currents. To examine mGluR1 activity when only one dimer subunit has access to
      glutamate ligand, wildtype mGluR1 was coexpressed with mGluR1 Y74A, a mutant with
      impaired glutamate binding, and the activity of the heterodimer (mutant/wild
      type) was examined. The mGluR1 Y74A mutant alone had a dose-response curve that
      was shifted by about 2 orders of magnitude. The half-maximal dose of glutamate
      shifted from 1.3 (wild-type mGluR1) to about 450 (mGluR1 Y74A) microM. However,
      the maximal effect was similar. Wild-type mGluR1 was expressed with excess Y74A
      mGluR1 to generate a receptor population consisting largely of mutant homodimers
      and mutant/wild-type heterodimers but without detectable wild-type homodimers.
      Under these conditions, no glutamate-mediated calcium current inhibition was
      observed below approximately 300 microM glutamate, although wild-type mGluR1
      protein was detectable with immunofluorescence. These data suggest that
      mutant/wild-type heterodimeric receptors are inactive at ligand concentrations
      favoring glutamate association with receptor dimers at only one subunit.

PMID- 15466248
TI  - Up-regulation of P-glycoprotein expression in small intestine under chronic
      serotonin-depleted conditions in rats.
AB  - To investigate the role of serotonin (5-HT), an important neurotransmitter and
      hormone/paracrine agent in the small intestine, in the transport activity of P
      glycoprotein (P-gp), the intestinal transport of quinidine, a P-gp substrate, was
      examined in 5-HT-depleted rats prepared by intraperitoneal administration of p
      chlorophenylalanine, a specific inhibitor of tryptophan hydroxylase in 5-HT
      biosynthesis. In the in vitro transport study, quinidine transport across rat
      jejunum was significantly enhanced in both the secretory and absorptive
      directions under 5-HT-depleted conditions, although the secretory transport was
      still predominant. The electrophysiological study suggested that the quinidine
      transport via passive diffusion was enhanced presumably through a paracellular
      route. This might be due to looser tight junctions under 5-HT-depleted
      conditions. The voltage-clamp technique clearly indicated that the secretory
      transport of quinidine through the transcellular pathway was also enhanced by the
      depletion of 5-HT. Furthermore, 5-HT depletion increased verapamil-sensitive
      secretory transport of quinidine in rat jejunum. These results indicate that the
      secretory transport of quinidine via P-gp was significantly enhanced under 5-HT
      depleted conditions. The level of ATP, an energy source for functioning P-gp, wet
      weight of jejunum, and total protein level in rat jejunal mucosa were not changed
      by 5-HT depletion, but the expression of P-gp in the brush-border membrane of rat
      jejunum was significantly induced, which is partly responsible for the
      enhancement of P-gp activity under the 5-HT-depleted condition.

PMID- 15466249
TI  - Abrogation of apoptosis through PDGF-BB-induced sulfated glycosaminoglycan
      synthesis and secretion.
AB  - Platelet-derived growth factor (PDGF)-BB-stimulated glycosaminoglycan (GAG)
      synthesis/secretion in fetal lung fibroblasts is dependent on sequential
      activation of the PDGF beta-receptor, phosphatidylinositol 3-kinase (PI3K), the
      serine/threonine kinase Akt-1,2, and the GTPase Rab3D. Because the Akt pathway
      has been implicated in cell survival mechanisms, we investigated whether the
      pathway regulating GAG synthesis/secretion was antiapoptotic. PDGF-BB treatment
      protected fetal lung fibroblasts against serum starvation-induced apoptosis,
      whereas wortmannin, an inhibitor of PI3K, abrogated this protective effect.
      Transfection of constitutively active Akt into fetal lung fibroblasts also
      safeguarded the cells from apoptosis induced by serum starvation. To determine
      whether the antiapoptotic response was due, at least in part, to GAGs, we treated
      lung fibroblasts with beta-D-xyloside as well as with topically applied GAGs,
      specifically those produced by fetal lung fibroblasts. beta-D-xyloside increased
      GAG synthesis/secretion and diminished apoptosis. Application of sulfated GAGs,
      chondroitin sulfate, and heparan sulfate, but not nonsulfated hyaluronan, also
      resulted in diminished apoptosis. Moreover, topically applied sulfated GAGs
      increased Bcl-associated death promoter phosphorylation and diminished caspase-3
      and -7 cleavage, indicating an antiapototic response. These data are compatible
      with the PDGF-BB-GAG signaling pathway regulating programmed fibroblast death in
      the fetal lung.

PMID- 15466250
TI  - Mechanism of eosinophil induced signaling in cholinergic IMR-32 cells.
AB  - Eosinophils interact with nerve cells, leading to changes in neurotransmitter
      release, altered nerve growth, and protection from cytokine-induced apoptosis. In
      part, these interactions occur as a result of activation of neural nuclear factor
      (NF)-kappaB, which is activated by adhesion of eosinophils to neural
      intercellular adhesion molecule-1 (ICAM-1). The mechanism and consequence of
      signaling after eosinophil adhesion to nerve cells were investigated. Eosinophil
      membranes, which contain eosinophil adhesion molecules but not other eosinophil
      products, were coincubated with IMR-32 cholinergic nerve cells. The studies
      showed that there were two mechanisms of activation of NF-kappaB, one of which
      was dependent on reactive oxygen species, since it was inhibited with
      diphenyleneiodonium. This occurred at least 30 min after coculture of eosinophils
      and nerves. An earlier phase of NF-kappaB activation occurred within 2 min of
      eosinophil adhesion and was mediated by tyrosine kinase-dependent phosphorylation
      of interleukin-1 receptor-associated kinase-1 (IRAK-1). Coimmunoprecipitation
      experiments showed that both extracellular signal-regulated kinase 1/2 and IRAK-1
      were recruited to ICAM-1 rapidly after coculture with eosinophil membranes. This
      was accompanied by an induction of ICAM-1, which was mediated by an IRAK-1
      dependent pathway. These data indicate that adhesion of eosinophils to IMR-32
      nerves via ICAM-1 leads to important signaling events, mediated via IRAK-1, and
      these in turn lead to expression of adhesion molecules.

PMID- 15466251
TI  - Modulatory effects of ozone on THP-1 cells in response to SP-A stimulation.
AB  - Ozone (O(3)), a major component of air pollution and a strong oxidizing agent,
      can lead to lung injury associated with edema, inflammation, and epithelial cell
      damage. The effects of O(3) on pulmonary immune cells have been studied in
      various in vivo and in vitro systems. We have shown previously that O(3) exposure
      of surfactant protein (SP)-A decreases its ability to modulate proinflammatory
      cytokine production by cells of monocyte/macrophage lineage (THP-1 cells). In
      this report, we exposed THP-1 cells and/or native SP-A obtained from
      bronchoalveolar lavage of patients with alveolar proteinosis to O(3) and studied
      cytokine production and NF-kappaB signaling. The results showed 1) exposure of
      THP-1 cells to O(3) significantly decreased their ability to express TNF-alpha in
      response to SP-A; TNF-alpha production, under these conditions, was still
      significantly higher than basal (unstimulated) levels in filtered air-exposed THP
      1 cells; 2) exposure of both THP-1 cells and SP-A to O(3) did not result in any
      significant differences in TNF-alpha expression compared with basal levels; 3)
      O(3) exposure of SP-A resulted in a decreased ability of SP-A to activate the NF
      kappaB pathway, as assessed by the lack of significant increase and decrease of
      the nuclear p65 subunit of NF-kappaB and cytoplasmic IkappaBalpha, respectively;
      and 4) O(3) exposure of THP-1 cells resulted in a decrease in SP-A-mediated THP-1
      cell responsiveness, which did not seem to be mediated via the classic NF-kappaB
      pathway. These findings indicate that O(3) exposure may mediate its effect on
      macrophage function both directly and indirectly (via SP-A oxidation) and by
      involving different mechanisms.

PMID- 15466252
TI  - Immunoregulatory effects of regulated, lung-targeted expression of IL-10 in vivo.
AB  - Regulation of pulmonary inflammation involves an intricate balance of both pro-
      and anti-inflammatory mediators. Acute lung injury can result from direct
      pulmonary insults that activate alveolar macrophages to respond with increased
      cytokine expression. Such cytokine gene expression is mediated in part via NF
      kappaB. IL-10 has been previously identified as an important endogenous anti
      inflammatory cytokine in vivo on the basis of inhibiting NF-kappaB activation;
      however, the mechanism of this inhibition remains incompletely defined. We
      hypothesized that IL-10 regulated NF-kappaB activation in vivo via IkappaK
      inhibition. A bitransgenic mouse that allowed for externally regulated, lung
      specific human IL-10 overexpression was generated. In the bitransgenic mice,
      introduction of doxycycline induced lung-specific, human IL-10 overexpression.
      Acute induction of IL-10 resulted in significant decreases in bronchoalveolar
      lavage fluid neutrophils (48%, P = 0.03) and TNF (62%, P < 0.01) following
      intratracheal LPS compared with bitransgenic negative mice. In vitro kinase
      assays showed this decrease to correlate to diminished lung IkappaK activity.
      Furthermore, we also examined the effect of chronic IL-10 overexpression in these
      transgenic mice. Results show that IL-10 overexpression in lungs of mature mice
      increased the number of intrapulmonary cells the phenotype of which was skewed
      toward increased B220+/CD45+ B cells and CD4+ T cells and was associated with
      increased CC chemokine expression. Thus regulated, lung-specific IL-10
      overexpression may have a variety of complex immunologic effects depending on the
      timing and duration of expression.

PMID- 15466253
TI  - Myeloperoxidase and protein oxidation in the airways of young children with
      cystic fibrosis.
AB  - Cystic fibrosis (CF) is characterized by considerable oxidative stress. However,
      it is not known whether oxidative stress is an important feature early in this
      disease. We have investigated a group of infants and young children with CF to
      establish whether oxidants are produced in their airways. Bronchoalveolar lavage
      fluid (BALF) was assayed for myeloperoxidase as a measure of neutrophilic
      inflammation, and 3-chlorotyrosine as a biomarker of the potent oxidant
      hypochlorous acid, which is formed by myeloperoxidase. Protein carbonyls were
      also measured as a nonspecific indicator of reactive oxidant production.
      Myeloperoxidase and 3-chlorotyrosine levels in BALF from children with CF were 10
      and fivefold higher, respectively, than in disease control subjects. There was a
      strong correlation between myeloperoxidase and 3-chlorotyrosine. Myeloperoxidase
      levels were fourfold higher in children with infections in their airways. Median
      protein carbonyls were elevated by only twofold compared with disease control
      subjects, but some children had extremely high levels of protein oxidation. We
      conclude that hypochlorous acid is produced early in CF and that it is a
      candidate for precipitating the fatal decline in lung function associated with
      this disease. Also, there must be other sourcesof oxidants because protein
      carbonyls were not related to either inflammation or infection.

PMID- 15466254
TI  - Endotoxin-induced chorioamnionitis modulates innate immunity of monocytes in
      preterm sheep.
AB  - The preterm fetus is immune naive and has immature innate immune function.
      Although the preterm fetus is frequently exposed to chorioamnionitis, the effects
      of exposure of the fetal lung to inflammation on innate immune responses are
      unknown. Using the fetal sheep model of chorioamnionitis, cord blood monocytes
      were isolated from preterm lambs 1 to 14 days after intra-amniotic endotoxin
      injection, cultured for approximately 16 hours, and challenged with endotoxin in
      vitro. Compared with monocytes from adult sheep, the preterm monocytes produced
      less H(2)O(2) and interleukin-6, and toll-like receptor 4 expression was
      decreased. Three days after intra-amniotic endotoxin exposure, preterm monocyte
      responses to in vitro endotoxin challenge demonstrated decreased H(2)O(2) and
      interleukin-6 production and decreased CD14 and major histocompatibility complex
      class II expression. Preterm monocyte responses 7 to 14 days after endotoxin
      tended to exceed those of adults and preterm control animals indicating augmented
      function. In contrast, a second intra-amniotic endotoxin injection 7 days after
      the initial endotoxin exposure suppressed monocyte function at 14 days. The fetal
      monocytes demonstrated patterns of responses consistent with endotoxin tolerance
      (immune paralysis) as well as maturation of function. Modulation of fetal innate
      immune responses by exposure to inflammation may alter subsequent immune
      adaptation after birth.

PMID- 15466255
TI  - Bone mineral density in lymphangioleiomyomatosis.
AB  - Estrogen deficiency and pulmonary diseases are associated with bone mineral
      density (BMD) loss. Lymphangioleiomyomatosis (LAM), a disorder affecting women
      that is characterized by cystic lung lesions, is frequently treated with
      antiestrogen therapy, i.e., progesterone and/or oophorectomy. Therefore, we
      evaluated BMD yearly in 211 LAM patients to determine the prevalence of BMD
      abnormalities, whether antiestrogen therapy decreased BMD, and if treatment with
      bisphosphonates prevented bone loss. Abnormal BMD was found in 70% of the
      patients and correlated with severity of lung disease and age. Greater severity
      of lung disease, menopause, and oophorectomy were associated with greater decline
      in BMD. After adjusting for differences in initial lung function and BMD, we
      found similar rates of BMD decline in progesterone-treated (n = 122) and
      untreated patients (n = 89). After similar adjustments, we found that
      bisphosphonate-treated patients (n = 98) had lower rates of decline in lumbar
      spine BMD (-0.004 +/- 0.003 vs. -0.015 +/- 0.003 gm/cm(2), p = 0.036) and T
      scores (-0.050 +/- 0.041 vs. -0.191 +/- 0.041, p < 0.001) than untreated patients
      (n = 113). We conclude that abnormal BMD was frequent in LAM. Progesterone
      therapy was not associated with changes in BMD; bisphosphonate therapy was
      associated with lower rates of bone loss. We recommend systematic evaluation of
      BMD and early treatment with bisphosphonates for patients with LAM.

PMID- 15466256
TI  - The molecular basis of Goodpasture and Alport syndromes: beacons for the
      discovery of the collagen IV family.

PMID- 15466257
TI  - Intraflagellar transport and cilia-dependent renal disease: the ciliary
      hypothesis of polycystic kidney disease.
AB  - Epithelial cells that line mammalian kidney nephrons have solitary nonmotile
      primary cilium projecting from their surface into the lumens of the ducts and
      tubules. Mutations that block the assembly of these cilia cause cystic kidney
      disease. The products of human autosomal dominant and recessive polycystic kidney
      disease genes and products of the nephronophthisis disease genes are at least
      partially localized to primary cilia. This suggests that the cilium serves as an
      organizing center for the early steps of the signal transduction pathway that is
      responsible for monitoring the integrity of the kidney nephron and controlling
      cell proliferation and differentiation.

PMID- 15466258
TI  - Extracellular hypotonicity increases Na,K-ATPase cell surface expression via
      enhanced Na+ influx in cultured renal collecting duct cells.
AB  - In the renal collecting duct (CD), the Na,K-ATPase, which provides the driving
      force for Na+ absorption, is under tight multifactorial control. Because CD cells
      are physiologically exposed to variations of interstitial and tubular fluid
      osmolarities, the effects of extracellular anisotonicity on Na,K-ATPase cell
      surface expression were studied. Results show that hypotonic conditions
      increased, whereas hypertonic conditions had no effect on Na,K-ATPase cell
      surface expression in confluent mpkCCDcl4 cells. Incubating cells with
      amphotericin B, which increases [Na+]i, under isotonic or anisotonic conditions,
      revealed that Na,K-ATPase recruitment to the cell surface was not directly
      related to variations of cell volume and osmolarity. The effects of amphotericin
      B and extracellular hypotonicity were not additive, and both were prevented by
      protein kinase A and proteasome inhibitors, suggesting a common mechanism of
      action. In line with this hypothesis, extracellular hypotonicity induced a
      sustained stimulation of the amiloride-sensitive short-circuit current,
      indicating increased Na+ influx through the apical epithelial Na+ channel.
      Moreover, inhibiting apical Na+ entry by amiloride, a blocker of epithelial Na+
      channel, or incubating cells in Na+ -free medium prevented the cell surface
      recruitment of Na,K-ATPase in response to extracellular hypotonicity. Altogether,
      these findings strongly suggest that extracellular hypotonicity stimulates apical
      Na+ influx leading to increased [Na+]i, protein kinase A activation, and
      recruitment of Na,K-ATPase units to the cell surface of mpkCCDcl4 cells.

PMID- 15466259
TI  - Feline polycystic kidney disease mutation identified in PKD1.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a commonly inherited
      disorder in humans that causes the formation of fluid-filled renal cysts, often
      leading to renal failure. PKD1 mutations cause 85% of ADPKD. Feline PKD is
      autosomal dominant and has clinical presentations similar to humans. PKD affects
      approximately 38% of Persian cats worldwide, which is approximately 6% of cats,
      making it the most prominent inherited feline disease. Previous analyses have
      shown significant linkage between the PKD phenotype and microsatellite markers
      linked to the feline homolog for PKD1. In this report, the feline PKD1 gene was
      scanned for causative mutations and a C>A transversion was identified at c.10063
      (human ref NM_000296) in exon 29, resulting in a stop mutation at position 3284,
      which suggests a loss of approximately 25% of the C-terminus of the protein. The
      same mutation has not been identified in humans, although similar regions of the
      protein are truncated. The C>A transversion has been identified in the
      heterozygous state in 48 affected cats examined, including 41 Persians, a
      Siamese, and several other breeds that have been known to outcross with Persians.
      In addition, the mutation is segregating concordantly in all available PKD
      families. No unaffected cats have been identified with the mutation. No
      homozygous cats have been identified, supporting the suggestion that the mutation
      is embryonic lethal. These data suggest that the stop mutation causes feline PKD,
      providing a test to identify cats that will develop PKD and demonstrating that
      the domestic cat is an ideal model for human PKD.

PMID- 15466260
TI  - OFD1 is a centrosomal/basal body protein expressed during mesenchymal-epithelial
      transition in human nephrogenesis.
AB  - OFD1 is the gene responsible for the oral-facial-digital syndrome type 1, a cause
      of inherited cystic renal disease. The protein contains an N-terminal LisH motif,
      considered important in microtubule dynamics, and several putative coiled-coil
      domains. This study used a combination of microscopic, biochemical, and
      overexpression approaches to demonstrate that OFD1 protein is a core component of
      the human centrosome throughout the cell cycle. Using a series of GFP-OFD1
      deletion constructs, it was determined that the N-terminus containing the LisH
      domain is not required for centrosomal localization; however, coiled-coil domains
      are critical, with at least two being necessary for centrosomal targeting.
      Importantly, most reported OFD1 mutations are predicted to cause protein
      truncation with loss of coiled-coil domains, presumably leading to loss of
      centrosomal localization. Kidney development constitutes a classic model of
      mesenchymal-epithelial transformation. By immunoprobing human metanephroi and
      kidney epithelial lines, it was found that, during acquisition of epithelial
      polarity, OFD1 became localized to the apical zone of nephron precursor cells and
      then to basal bodies at the origin of primary cilia in fully differentiated
      epithelia. These striking patterns of OFD1 localization within cells place the
      protein at key sites, where it may play roles not only in microtubule
      organization (centrosomal function) but also in mechanosensation of urine flow (a
      primary ciliary function).

PMID- 15466261
TI  - Divergent expression patterns for hypoxia-inducible factor-1beta and aryl
      hydrocarbon receptor nuclear transporter-2 in developing kidney.
AB  - The hypoxia-inducible factors (HIF) are alpha/beta heterodimeric transcription
      factors of the basic helix-loop-helix-Per-Arnt-Sim (bHLH-PAS) superfamily and are
      chiefly responsible for cellular adaptation to oxygen deprivation. HIF function
      relies on the stabilization of the alpha subunit. When oxygen tension falls, HIF
      alpha subunits translocate to the nucleus and, upon dimerization with HIF-beta,
      activate transcription of target genes, including vascular endothelial growth
      factor, vascular endothelial growth factor receptor-1 and -2, and WT-1, which are
      vital for kidney development. HIF-beta subunits are stable regardless of oxygen
      concentration and constitutively translocate to the nucleus. It was shown
      previously that HIF-1beta protein expression is nearly ubiquitous in newborn
      kidney and that HIF-1beta dimerizes with either HIF-1alpha or -2alpha. Here it is
      shown that aryl hydrocarbon receptor nuclear transporter-2 (ARNT2/HIF-2beta) also
      heterodimerized with HIF-1alpha and -2alpha. ARNT2/HIF-2beta protein was highly
      expressed in newborn kidney but decreased significantly with age, whereas HIF
      1beta levels remained relatively constant. By immunohistochemical analysis,
      widespread expression of HIF-1beta was observed in developing and mature kidneys.
      ARNT2/HIF-2beta protein distribution was restricted to distal segments of
      developing nephrons and in mature kidney was confined specifically to thick
      ascending limb of Henle's loop. The data presented here suggest that ARNT2/HIF
      2beta is required at high levels during nephrogenesis in distal tubules and later
      exclusively in thick ascending limb. Furthermore, Hypoxyprobe-1 and lotus lectin
      co-localization studies showed that developing proximal convoluted tubules were
      the most severely hypoxic nephron segment in immature kidney. Because HIF-2beta
      protein was not abundantly expressed in this segment, it may not be engaged in
      mediating responses to severe hypoxia. The differential distribution patterns for
      HIF-1beta and -2beta suggest divergent roles during kidney development for these
      highly related bHLH-PAS proteins.

PMID- 15466262
TI  - Calcimimetic compound upregulates decreased calcium-sensing receptor expression
      level in parathyroid glands of rats with chronic renal insufficiency.
AB  - The reduced expression level of the calcium-sensing receptor (CaR) is attributed
      to the hyposensitivity of parathyroid cells to extracellular calcium
      concentration [Ca2+]o, which plays a crucial role in the pathogenesis of
      secondary hyperparathyroidism (SHPT) in patients and rats with chronic renal
      insufficiency (CRI). Calcimimetic compounds have been demonstrated to improve the
      decreased sensitivity of CaR to extracellular calcium concentration and to
      suppress both parathyroid hormone (PTH) oversecretion and parathyroid cell
      proliferation. However, the effect of calcimimetics on the reduced CaR expression
      level in parathyroid cells in CRI remains unclarified. The aim of this
      investigation was to examine the effect of the calcimimetic compound NSP R-568 (R
      568) on the CaR expression in the parathyroid cells of rats with experimental
      CRI. Subtotally nephrectomized rats were fed a high-phosphorus diet for 8 (n =
      12; Nx-8 group) or 9 wk (n = 11; Nx-9 group) to induce severe SHPT. Another group
      of uremic rats were fed a high-phosphorus diet for 8 wk and then orally
      administered R-568 (100 micromol/kg body wt) once a day for 7 d (n = 11; Nx+R-568
      group). Sham-operated rats that were fed a standard diet for 9 wk were used as
      controls (n = 8). R-568 treatment induced a significant reduction in plasma PTH
      level with significant decrease in serum calcium and without change in serum
      phosphorus concentration. Serum 1,25(OH)2D3 level was not affected by R-568
      administration. CaR mRNA and protein levels in the Nx-8 and Nx-9 groups
      significantly decreased compared with those in the controls; however, no
      significant difference in these parameters was observed between the Nx-8 and Nx-9
      groups. In the Nx+R-568 group, CaR mRNA and protein levels significantly
      increased compared with those in either the Nx-8 or Nx-9 group. R-568 was
      effective in reducing the number of proliferating cell nuclear antigen-positive
      cells along with parathyroid gland growth suppression in the Nx+R-568 group
      compared with that in the Nx-9 group. The results suggest that the calcimimetic
      compound R-568 upregulates decreased CaR expression, and the upregulation
      possibly has an enhancement effect on PTH secretion and parathyroid cell
      hyperplasia through the improved sensitivity of CaR to [Ca2+]o.

PMID- 15466263
TI  - Intravenous delivery of PTH/PTHrP type 1 receptor cDNA to rats decreases heart
      rate, blood pressure, renal tone, renin angiotensin system, and stress-induced
      cardiovascular responses.
AB  - While parathyroid hormone type 1 receptor (PTH1R)-mediated vasodilatory, cardiac
      stimulatory, and renin-activating effects of exogenous PTH/PTH-related protein
      (PTHrP) are acknowledged, interactions of endogenous PTHrP with these systems
      remain unclear, mainly because the unavailability of viable PTHrP/PTH1R knockout
      mice. Transgenic mice overexpressing PTH1R in smooth muscle strongly have
      supported the PTHrP/PTH1R system as a cardiovascular system (CVS) regulator, but
      the consequences on renovascular (RVS) and renin-angiotensin systems (RAS) have
      not been explored in these studies. The aim was to develop a model in which one
      could study the consequences on CVS, RVS, and RAS of generalized PTH1R
      overexpression. Systemic PTH1R cDNA plasmid delivery was used in adult rats, a
      system that is amenable to studies in isolated perfused kidneys and that
      minimizes development-induced compensatory mechanisms. Intravenous administration
      of hPTH1R or green fluorescence protein-tagged hPTH1R in pcDNA3 resulted 3 wk
      later, in generalized expression of hPTH1R (mRNA and protein), especially in
      vessels, liver, heart, kidney, and central nervous system, where it is expressed
      physiologically. As expected, PTH1R overexpression decreased BP and renal tone.
      Unexpected, however, PTH1R overexpression decreased heart rate. These studies
      also revealed that endogenous PTHrP actually inhibits renin release and that
      hPTH1R overexpression tends to increase that effect. Striking, liver production
      and circulatory level of angiotensinogen and hence plasma renin activity were
      markedly reduced. Thus, abrupt PTH1R overexpression in adult rats profoundly
      alters the CVS, RVS, and RAS, strongly supporting the PTH/PTHrP/PTH1R system as
      crucial for heart and vascular tone regulation. In addition, these results
      revealed that PTH1R-mediated mechanisms might have protective effects against
      cardiovascular stress-induced responses, including stimulations in heart rate and
      RAS.

PMID- 15466264
TI  - Endothelin A receptor antagonism and angiotensin-converting enzyme inhibition are
      synergistic via an endothelin B receptor-mediated and nitric oxide-dependent
      mechanism.
AB  - Animal studies suggest that endothelin A (ETA) receptor antagonism and
      angiotensin-converting enzyme (ACE) inhibition may be synergistic. This
      interaction and the role of ETB receptors and endothelial mediators were
      investigated in terms of systemic and renal effects in humans in two studies. In
      one study, six subjects received placebo, the ETA receptor antagonist BQ-123
      alone, and BQ-123 in combination with the ETB receptor antagonist BQ-788 after
      pretreatment with the ACE inhibitor enalapril (E) or placebo. In the other, six
      subjects who were pretreated with E received placebo, BQ-123, and BQ-123 with
      concomitant inhibition of nitric oxide (NO) synthase or cyclo-oxygenase (COX).
      Both were randomized, double-blind, crossover studies. Mean arterial pressure was
      reduced by BQ-123, an effect that was doubled during ACE inhibition (mean area
      under curve +/- SEM; BQ-123, -2.3 +/- 1.8%; BQ-123+E, -5.1 +/- 1.1%; P < 0.05
      versus placebo). BQ-123 increased effective renal blood flow (BQ-123, -0.1 +/-
      2.4%; BQ-123+E, 10.9 +/- 4.2%; P < 0.01 versus BQ-123), reduced effective renal
      vascular resistance (BQ-123, -1.2 +/- 3.1%; BQ-123+E, -12.8 +/- 3.0%; P < 0.01
      versus placebo and versus BQ-123), and increased urinary sodium excretion
      markedly (BQ-123, 2.6 +/- 12.8%; BQ-123+E, 25.2 +/- 12.6%; P < 0.05 versus BQ
      123, P < 0.01 versus placebo and versus E) only during ACE inhibition. These
      effects were abolished by both ETB receptor blockade and NO synthase inhibition,
      whereas COX inhibition had no effect. In conclusion, the combination of ETA
      receptor antagonism and ACE inhibition is synergistic via an ETB receptor
      mediated, NO-dependent, COX-independent mechanism. The reduction of BP and renal
      vascular resistance and associated substantial natriuresis make this a
      potentially attractive therapeutic combination in renal disease.

PMID- 15466265
TI  - Podocytes are firmly attached to glomerular basement membrane in kidneys with
      heavy proteinuria.
AB  - Glomerular epithelial cells (podocytes) play an important role in the
      pathogenesis of proteinuria. Podocyte foot process effacement is characteristic
      for proteinuric kidneys, and genetic defects in podocyte slit diaphragm proteins
      may cause nephrotic syndrome. In this work, a systematic electron microscopic
      analysis was performed of the structural changes of podocytes in two important
      nephrotic kidney diseases, congenital nephrotic syndrome of the Finnish type and
      minimal-change nephrotic syndrome (MCNS). The results showed that (1) podocyte
      foot process effacement was present not only in proteinuric glomeruli but also in
      nonproteinuric MCNS kidneys; (2) podocytes in proteinuric glomeruli did not show
      detachment from the basement membrane or cell membrane ruptures; (3) the number
      of pinocytic membrane invaginations in the basal and apical parts of the
      podocytes was comparable in proteinuric and control kidneys; (4) in proteinuric
      kidneys, the podocyte slit pore density was decreased by 69 to 80% and up to half
      of the slits were so "tight" that no visible space between foot processes was
      seen; thus, the filtration surface area between podocytes was dramatically
      reduced; and (5) in the narrow MCNS slit pores, nephrin was located in the apical
      part of the podocyte foot process, indicating vertical transfer of the slit
      diaphragm complex in proteinuria. In conclusion, these results suggest that
      protein leakage in the two nephrotic syndromes studied occurs through defective
      podocyte slits, and the other structural alterations commonly seen in electron
      microscopy are secondary to, not a prerequisite for, the development of
      proteinuria.

PMID- 15466266
TI  - Tranilast attenuates structural and functional aspects of renal injury in the
      remnant kidney model.
AB  - Pathologic fibrosis is a key feature of progressive renal disease that correlates
      closely with kidney dysfunction and in which the prosclerotic growth factor TGF
      beta has been consistently implicated. Tranilast (n-[3,4-dimethoxycinnamoyl]
      anthranilic acid), an antifibrotic agent that is used to treat hypertrophic scars
      and scleroderma, has also been shown to inhibit TGF-beta-induced extracellular
      matrix synthesis in a range of cell types, including those of renal origin.
      Therefore, the effects of tranilast on kidney fibrosis and dysfunction were
      examined in the subtotal nephrectomy model of progressive renal injury. Subtotal
      nephrectomy led to proteinuria and renal dysfunction in association with
      glomerulosclerosis, tubulointerstitial fibrosis, and macrophage accumulation.
      Despite persistent hypertension, treatment with tranilast led to a reduction in
      albuminuria (61.7 (x)/(/) 1.2 versus 20.5 (x)/(/) 1.3 mg/d; P < 0.01) and plasma
      creatinine (0.16 versus 0.08 mmol/L; P < 0.01) in subtotally nephrectomized rats.
      In addition, features suggestive of TGF-beta activation, including
      glomerulosclerosis, tubulointerstitial fibrosis, tubular atrophy, and macrophage
      accumulation, all were significantly attenuated by tranilast in association with
      evidence of reduced TGF-beta signaling in vivo. In the context of a recent pilot
      study in humans, the findings of the present report suggest that tranilast may
      provide a novel strategy for the treatment of progressive kidney disease
      characterized by fibrotic scarring.

PMID- 15466267
TI  - Chronic uremia attenuates growth hormone-induced signal transduction in skeletal
      muscle.
AB  - Malnutrition and muscle wasting are common in chronic renal failure (CRF) and
      adversely affect morbidity and mortality. Contributing to the muscle wasting is
      resistance to growth hormone (GH). For testing whether impaired GH signaling is a
      cause of the skeletal muscle GH resistance and for elucidating its mechanisms,
      muscle GH signaling and action were studied in GH-deficient rats with surgically
      induced CRF and sham-operated pairfed control rats. GH treatment increased
      gastrocnemius muscle IGF-1 mRNA levels significantly in control but not in CRF
      rats. GH-activated Janus-associated kinase 2 (JAK2)-signal transducers and
      activators of transcription 5 (STAT5) signaling was impaired in CRF rats, despite
      normal GH receptor (GHR), JAK2, and STAT5 protein levels. Phosphorylation of the
      GHR, JAK2, and STAT5 in response to GH was depressed by nearly half in CRF (P <
      0.05), and nuclear phospho-STAT5 levels were depressed by approximately one third
      (P < 0.01). GH-stimulated suppressors of cytokine signaling 2 mRNA levels were
      significantly higher in CRF. This may be related to inflammatory cytokine
      activity because C-reactive protein levels were elevated. Muscle protein-tyrosine
      phosphatase activity was also increased significantly by twofold. In conclusion,
      rats with CRF acquire skeletal muscle resistance to GH that is caused at least in
      part by impaired JAK2-GHR-STAT5 phosphorylation and nuclear STAT5 translocation.
      Furthermore, it seems that the attenuated JAK2-STAT5 phosphorylation may be
      caused by at least two different processes. One involves depressed
      phosphorylation of the signaling proteins because of increased suppressors of
      cytokine signaling 2 expression that may be linked to low-grade inflammation. The
      other may involve increased signaling protein dephosphorylation because of
      heightened protein-tyrosine phosphatase activity.

PMID- 15466268
TI  - Intravenous administration of hepatocyte growth factor gene ameliorates diabetic
      nephropathy in mice.
AB  - Diabetic nephropathy is characterized by progressive loss of renal function,
      persistent proteinuria, and relentless accumulation of extracellular matrix
      leading to glomerulosclerosis and interstitial fibrosis. This study investigated
      the potential effects of long-term expression of exogenous hepatocyte growth
      factor (HGF) on normal and diabetic kidneys. Intravenous injection of human HGF
      gene via naked plasmid vector resulted in abundant HGF protein specifically
      localized in renal glomeruli, despite an extremely low level of transgene mRNA in
      the kidney. In uninephrectomized mice made diabetic with streptozotocin, delivery
      of exogenous HGF gene ameliorated the progression of diabetic nephropathy. HGF
      attenuated urine albumin and total protein excretion in diabetic mice. Exogenous
      HGF also mitigated glomerular mesangial expansion, reduced fibronectin and type I
      collagen deposition, and prevented interstitial myofibroblast activation. In
      addition, HGF prevented kidney cells from apoptotic death in the glomeruli and
      tubulointerstitium. Moreover, expression of HGF inhibited renal expression of TGF
      beta1 and reduced urine level of TGF-beta1 protein. Therefore, despite the
      effects of HGF on diabetic nephropathy being controversial, these observations
      suggest that supplementation of HGF is beneficial in ameliorating diabetic renal
      insufficiency in mice.

PMID- 15466269
TI  - Delayed DMSO administration protects the kidney from mercuric chloride-induced
      injury.
AB  - Reactive oxygen species are implicated as mediators of tissue damage in ischemic
      and toxic acute renal failure. Whereas many agents can inhibit renal ischemic
      injury, only hepatocyte growth factor, melatonin, N-acetylcysteine, and DMSO
      inhibit injury after mercuric chloride administration. Although it has been
      suggested that DMSO may chelate the mercuric ion, more recent studies suggest
      that it has anti-inflammatory and antioxidant effects. Acute renal failure was
      induced by 5 mg/kg subcutaneous injection of mercuric chloride in BALB/c mice.
      DMSO (3.8 ml/kg, 40% in PBS) or vehicle (PBS) was injected intraperitoneally at 0
      and 24 h after mercuric chloride injection, or DMSO treatment was delayed 3 or 5
      h. DMSO prevented increases in serum creatinine and tubular damage at 24 and 48
      h. When DMSO treatment was delayed by 3 h, it was still beneficial; however, with
      a 5-h delay, the histology score and serum creatinine were not significantly
      decreased. DMSO partially prevented a mercuric chloride-induced decrease in
      glutathione peroxidase activity and completely prevented the transient decrease
      in superoxide dismutase activity. Neither mercuric chloride nor DMSO affected
      catalase activity significantly. For investigating possible effects of DMSO on
      cellular mercuric ion uptake, MDCK cells that were transfected with human organic
      anion transporter-1 were used. 203Hg uptake was inhibited 90% by N-acetylcysteine
      but only 5% by DMSO, indicating that the effect of DMSO is not related to
      chelating mercuric ion or inhibiting its uptake. It is concluded that DMSO acts
      in part as an antioxidant to inhibit mercuric chloride-induced acute renal
      injury.

PMID- 15466270
TI  - Vascular endothelial growth factor165 resolves glomerular inflammation and
      accelerates glomerular capillary repair in rat anti-glomerular basement membrane
      glomerulonephritis.
AB  - Vascular endothelial growth factor (VEGF) is essential for maintenance of the
      glomerular capillary network. The present study investigated the effects of VEGF
      in rats with progressive crescentic glomerulonephritis (GN). Necrotizing and
      crescentic GN was induced in rats by injection of anti-rat glomerular basement
      membrane (GBM) antibody. The alterations of glomerular capillaries and glomerular
      VEGF expression were assessed. In addition, the effects of continuous VEGF165
      administration (10 microg/100 g per d) on glomerular capillaries, glomerular
      inflammation, and the course of crescentic GN were examined. The appropriate
      timing of VEGF administration in progressive GN also was evaluated. In anti-GBM
      GN, necrotizing and crescentic glomerular lesions occurred by day 7, and newly
      formed necrotizing lesions reoccurred by week 3. Expression of VEGF was markedly
      reduced in necrotizing and crescentic lesions. Capillary repair was impaired
      after capillary destruction in necrotizing and crescentic glomeruli, which
      rapidly progressed to sclerotic glomeruli with chronic renal failure. In
      contrast, in the rats that received VEGF165 administration from day 7, the
      necrotizing and crescentic lesions recovered and renal function significantly
      improved in week 4. This was evident by proliferating endothelial cells and
      glomerular capillary repair. In addition, VEGF administration decreased
      intercellular adhesion molecule-1 and monocyte chemoattractant protein-1
      expression in glomeruli (particularly on endothelial cells), reduced glomerular
      infiltrating CD8-postive and ED-1-positive cells, and inhibited the newly formed
      necrotizing lesions. VEGF administration was apparently effective against both
      the inflammatory and necrotizing glomerular lesions. These results suggest that
      VEGF administration resolves glomerular inflammation and accelerates glomerular
      recovery in the progressive necrotizing and crescentic GN. The therapeutic
      application of VEGF may be clinically useful for severe GN accompanied by
      extensive glomerular inflammation and endothelial injury.

PMID- 15466271
TI  - Targeted deletion of angiotensin II type 1A receptor does not protect mice from
      progressive nephropathy of overload proteinuria.
AB  - In experimental and human renal diseases, progression is limited by angiotensin
      converting enzyme inhibitors. Whether renoprotection was due to their capacity of
      reducing proinflammatory and profibrotic effects of angiotensin II (Ang II) or
      limiting proteinuria and its long term toxicity is debated. For dissecting the
      relative contribution of Ang II and proteinuria to chronic renal damage, the
      protein-overload proteinuria model was used in genetically modified mice lacking
      the major isoform of murine AT1 receptor (AT1A). Uninephrectomized AT1A+/+ and -/
      mice received a daily injection of BSA or saline for 4 or 11 wk. AT1A-/-BSA mice
      acquired a renal phenotype of proteinuria and renal glomerular and
      tubulointerstitial lesions, albeit attenuated with respect to AT1A+/+BSA.
      Administration of the calcium channel blocker lacidipine to reduce BP of
      AT1A+/+BSA mice to levels of AT1A-/-BSA translated into comparable values of
      protein excretion rate and glomerular and tubulointerstitial injury in both
      strains. These results confirm that the toxic effect of protein trafficking on
      renal disease progression is not necessarily dependent on Ang II to the extent
      that targeted deletion of AT1A does not prevent disease progression. A role of
      Ang II via AT1B or AT2 receptors is still a possibility that cannot be ruled out
      by the present experimental approach. These findings provide a clear rationale
      for specifically targeting proteinuria in pharmacologic interventions of chronic
      nephropathies.

PMID- 15466272
TI  - Ischemia-reperfusion induces glomerular and tubular activation of proinflammatory
      and antiapoptotic pathways: differential modulation by rapamycin.
AB  - Ischemia-reperfusion (I-R) injury in transplanted kidney, a key pathogenic event
      of delayed graft function (DGF), is characterized by tubular cell apoptosis and
      interstitial inflammation. Akt-mammalian target of rapamycin-S6k and NF-kappaB
      inducing kinase (NIK)-NF-kappaB axis are the two main signaling pathways
      regulating cell survival and inflammation. Rapamycin, an immunosuppressive drug
      inhibiting the Akt axis, is associated with a prolonged DGF. The aim of this
      study was to evaluate Akt and NF-kappaB axis activation in patients who had DGF
      and received or not rapamycin and in a pig model of I-R and the role of
      coagulation priming in this setting. In graft biopsies from patients who were not
      receiving rapamycin, phosphorylated Akt increased in proximal tubular,
      interstitial, and mesangial cells with a clear nuclear translocation. The same
      pattern of activation was observed for S6k and NIK. However, in rapamycin-treated
      patients, a significant reduction of S6k but not Akt and NIK activation was
      observed. A time-dependent activation of phosphatidylinositol 3-kinase, Akt, S6k,
      and NIK was observed in the experimental model with the same pattern reported for
      transplant recipients who did not receive rapamycin. Extensive interstitial and
      glomerular fibrin deposition was observed both in pig kidneys upon reperfusion
      and in DGF human biopsies. It is interesting that the activation of both Akt and
      NIK-NF-kappaB pathways was induced by thrombin in cultured proximal tubular
      cells. In conclusion, the data suggest that (1) coagulation may play a pathogenic
      role in I-R injury; (2) the Akt axis is activated after I-R, and its inhibition
      may explain the prolonged DGF observed in rapamycin-treated patients; and (3) NIK
      activation in I-R and DGF represents a proinflammatory, rapamycin-insensitive
      signal, potentially leading to progressive graft injury.

PMID- 15466273
TI  - Long-term effects of in utero exposure to cyclosporin A on renal function in the
      rabbit.
AB  - The number of pregnant women who receive cyclosporin A (CsA) after
      transplantation or for autoimmune disease has increased. CsA and its metabolites
      can cross the placental barrier and thus interfere with fetal development. It was
      shown previously that rabbits that were exposed in utero to 10 mg/kg per d CsA
      from the 14th to the 18th day of gestation presented a 25% nephron reduction.
      Thus, this study was conducted to assess the long-term systemic and renal effects
      of a CsA-induced nephron reduction. Twenty-two pregnant New Zealand white rabbits
      were randomly divided into two groups: Twelve received 10 mg/kg per d CsA from
      day 14 to day 18 of gestation, and 10 were used as controls. Rabbits that were
      born to these animals were evaluated at 4, 11, 18, and 35 wk of life. Pups that
      were exposed antenatally to CsA presented first a permanent nephron deficit;
      second, glomerular, tubular, and intrarenal hemodynamics dysfunction; third,
      enlarged kidneys with numerous tubular and glomerular lesions; and, fourth, an
      endothelin-dependent systemic hypertension that worsened with age. In utero
      exposure to CsA induced a nephron reduction that led to systemic hypertension and
      progressive chronic renal insufficiency in adulthood. A long-term clinical survey
      is mandatory in infants who are born to mothers who were treated with cyclosporin
      during pregnancy.

PMID- 15466274
TI  - Management of lupus nephritis: an update.

PMID- 15466276
TI  - Impact of an exercise program on arterial stiffness and insulin resistance in
      hemodialysis patients.
AB  - Cardiovascular disease remains the primary cause of mortality in patients who are
      maintained on hemodialysis. Arterial stiffness and insulin resistance are
      independent risk factors for cardiovascular mortality in this population. In
      healthy individuals, higher physical conditioning is associated with reduced
      arterial stiffness. Exercise reduces insulin resistance and glucose intolerance
      in sedentary, overweight individuals and diabetic patients. The purpose of this
      study was to determine the impact of an exercise program on arterial stiffness
      and insulin resistance in a group of patients on hemodialysis. The effect of
      exercise training on arterial stiffness and insulin resistance in 11 patients who
      were on chronic hemodialysis was evaluated. Exercise classes of 1-h duration were
      conducted twice weekly for 3 mo. Arterial stiffness was assessed using the radial
      artery pressure waveform analysis. Aerobic exercise improved arterial stiffness
      from 17 +/- 3 u at baseline to 12.2 +/- 3 u at the end of the intervention (P =
      0.01). After 1 mo of detraining, arterial stiffness reverted to pre-exercise
      levels (17.3 +/- 3 u). Pulse pressure paralleled arterial stiffness changes, and
      the correlation between them was statistically significant (r = 0.725, P =
      0.012). Insulin resistance was calculated using the homeostatic model assessment
      formula. Exercise at the intensity and duration used in our study had no impact
      on insulin resistance (P = 0.38). These findings suggest that 3 mo of aerobic
      exercise training improves arterial stiffness, an independent risk factor for
      cardiovascular mortality in patients who are on hemodialysis, and has no impact
      on insulin resistance. The beneficial effect on arterial stiffness dissipates
      within 1 mo of detraining. To obtain therapeutic benefits, an exercise program
      for patients who are maintained on hemodialysis should be designed to promote
      regular long term exercise, >3 h/wk.

PMID- 15466275
TI  - Selective decrease in urinary aquaporin 2 and increase in prostaglandin E2
      excretion is associated with postobstructive polyuria in human congenital
      hydronephrosis.
AB  - This study was undertaken to determine the role of aquaporin 2 (AQP2) in the
      impaired urinary concentrating capacity observed in patients who underwent
      pyeloplasty because of congenital unilateral hydronephrosis as a result of
      pyeloureteral junction disease. Twelve children (mean age, 8 +/- 2 mo) were
      examined in the study. From day 1 to day 5 after surgery, the urine was collected
      separately from pyelostomy draining only from the postobstructed kidney and from
      the bladder catheter draining mostly from the contralateral kidney used as
      internal control. After pyeloplasty, the postobstructed kidney was characterized
      by a reduced urinary excretion of AQP2 (approximately 54%) associated with
      polyuria that persisted from day 1 to day 5 (433 +/- 58 versus 310 +/- 74 ml/24 h
      at day 1; 326 +/- 44 versus 227 +/- 26 ml/24 h at day 5). In parallel, urine
      osmolality from the postobstructed kidney was significantly reduced compared with
      the contralateral kidney (111 +/- 12 versus 206 +/- 49 at day 1; 136 +/- 24
      versus 235 +/- 65 mOsm/kg at day 5). Creatinine clearance from the postobstructed
      kidney was not significantly different compared with the contralateral kidney
      throughout the 4 d after surgery. However, on day 5, creatinine clearance from
      the postobstructed kidney became significantly lower. Prostaglandin E2 in the
      urine from postobstructed kidneys was found to be twofold higher than in the
      contralateral samples (26.0 +/- 6.7 versus 13.5 +/- 2.5 at day 5). It is
      concluded that (1) the selective downregulation of AQP2 in postobstructed kidney
      may account for the higher excretion of hypotonic urine, and (2) the local
      increase in prostaglandin E2 synthesis in postobstructed kidney may be involved
      in AQP2 downregulation and in maintaining a GFR similar to that of the
      contralateral kidney.

PMID- 15466278
TI  - Anti-erythropoietin antibody-mediated pure red cell aplasia after treatment with
      recombinant erythropoietin products: recommendations for minimization of risk.
AB  - Since 1998, there has been a marked increase in incidence of pure red cell
      aplasia secondary to development of anti-erythropoietin antibodies (Ab+ PRCA) in
      patients who have chronic kidney disease (CKD) and receive recombinant
      erythropoietin. The relationship between incidence of Ab+ PRCA and specific
      erythropoietin products has not been examined rigorously. Manufacturers provided
      data regarding exposure to erythropoietin products and incidence of Ab+ PRCA
      between January 1998 and March 2003 in patients with CKD. Assuming a Poisson
      distribution, a maximum likelihood estimate for the Poisson rate parameter was
      calculated for each product. A test for homogeneity of Poisson rates was
      conducted to compare likelihood estimates between products. Global incidence of
      Ab+ PRCA was relatively low. Likelihood estimates were not significantly
      different for Epogen, Procrit, and Aranesp, independent of their formulation or
      route of administration. Eprex lacking human serum albumin (HSA) and administered
      subcutaneously was associated with the greatest risk of Ab+ PRCA. HSA-containing
      Eprex administered subcutaneously was associated with a lower risk than HSA-free
      Eprex administered subcutaneously, but this risk exceeded that of intravenous
      Epogen and intravenous HSA-free Eprex. NeoRecormon administered subcutaneously
      was associated with less risk than subcutaneous HSA-free Eprex but more risk than
      intravenous Epogen. HSA-free Eprex should not be administered subcutaneously to
      patients with CKD due to increased risk of Ab+ PRCA. Although the subcutaneous
      administration of HSA-containing Eprex is riskier than intravenous Epogen and
      intravenous HSA-free Eprex, and the use of subcutaneous NeoRecormon is riskier
      than intravenous Epogen, there is currently no evidence that other products are
      safer.

PMID- 15466277
TI  - A genome scan for ESRD in black families enriched for nondiabetic nephropathy.
AB  - Nephropathy is a complex disorder, with predisposition influenced by the
      interplay of both genetic and environmental factors. As part of an effort to map
      genes that predispose to ESRD, a genome scan was performed in 264 black pedigrees
      that contained 296 ESRD-affected sibling pairs using multipoint nonparametric
      linkage analysis methods. The cause of ESRD in index cases was consistent with
      hypertension-associated ESRD. Nonparametric linkage (NPL) regression provided
      modest evidence of linkage to 9p21.3 near D9S1121 (logarithm of odds [LOD] =
      2.03), 1q25.1 near D1S1589 (LOD = 1.62), and 13q33.3 near D13S796 (LOD = 1.02).
      Adjusting for the evidence of linkage at the other loci through the NPL
      regression analysis provided evidence for linkage to 1q25.1, 6p23, and 9p21.3.
      The NPL regression and ordered subset analyses suggest that the evidence for
      linkage significantly increased with early onset of ESRD (2q32.1 LOD = 3.89,
      13q13.1 LOD = 3.90), increased BMI (8p22 LOD = 3.37, 13q33.3 LOD = 5.20, 18p11.3
      LOD = 2.38), early onset of hypertension (14q21.1 LOD = 3.19, 20q13.2 LOD =
      2.32), and late onset of hypertension (4q13.1 LOD = 3.44, 5p15.33 LOD = 2.82).
      Multipoint single-locus linkage analysis provided modest evidence of linkage to
      nondiabetic ESRD on 9p21.3, 1q25.1 (in the region of the podocin gene), and
      13q33.3. NPL regression and ordered subset analyses also identified loci on
      13q13.1 and 13q33.3 as contributing to early-onset ESRD and ESRD in the presence
      of increased BMI, respectively. These regions should receive priority in the
      search for loci that contribute susceptibility to nondiabetic nephropathy.

PMID- 15466279
TI  - Catheter-related interventions to prevent peritonitis in peritoneal dialysis: a
      systematic review of randomized, controlled trials.
AB  - As many as 15 to 50% of end-stage kidney disease patients are on peritoneal
      dialysis (PD), but peritonitis limits its more widespread use. Several PD
      catheter-related interventions (catheter designs, surgical insertion approaches,
      and connection methods) have been purported to reduce the risk of peritonitis in
      PD. The goal was to assess the trial evidence supporting their use. The Cochrane
      CENTRAL Registry, MEDLINE, EMBASE, and reference lists were searched for
      randomized trials of catheter types and related interventions in PD. Two
      reviewers extracted data on the rates of peritonitis and exit-site/tunnel
      infection, catheter removal/replacement, technique failure, and all-cause
      mortality. Analysis was by a random effects model, and results are expressed as
      relative risk and 95% confidence intervals. Thirty-seven eligible trials (2822
      patients) were identified: eight of surgical strategies of catheter insertion,
      eight of straight versus coiled catheters, 10 of Y-set versus conventional spike
      systems, four of Y-set versus double-bag systems, and seven of other
      interventions. Despite the large total number of patients, few trials covered the
      same interventions, small numbers of patients were enrolled in each trial, and
      the methodologic quality was suboptimal. Y-set and twin-bag systems were superior
      to conventional spike systems (seven trials, 485 patients; relative risk, 0.64;
      95% confidence intervals 0.53 to 0.77), and no other catheter-related
      intervention was demonstrated to prevent peritonitis in PD. This systematic
      review demonstrates that of all catheter-related interventions designed to
      prevent peritonitis in PD, only disconnect (twin-bag and Y-set) systems have been
      proved to be effective (compared with conventional spike systems). Despite the
      importance of PD as a renal replacement therapy modality and the large number of
      patients who receive it, it is still not known whether any particular PD catheter
      designs, implantation techniques, or modalities are effective, given the
      limitations of available trials.

PMID- 15466280
TI  - Plasma protein aspartyl damage is increased in hemodialysis patients: studies on
      causes and consequences.
AB  - Plasma proteins in hemodialysis patients display a significant increase in
      deamidated/isomerized Asx (asparagine and aspartic acid) content, a marker of
      protein fatigue damage. This has been linked to the toxic effects of
      hyperhomocysteinemia in uremic erythrocytes; however, treatment aimed at abating
      homocysteine levels did not lead to significant reductions in plasma protein
      damage. The hypothesis that lack of reduction in protein damage could be due to
      protein increased intrinsic instability, as result of interference with the
      uremic milieu rather than to hyperhomocysteinemia, was put forward. The
      deamidated/isomerized Asx content of normal plasma incubated with several uremic
      toxins for 24 h, 72 h, and 7 d was measured, identifying a group of toxins that
      were able to elicit this kind of damage. Uremic toxins were also incubated with
      purified human albumin, and dose-response experiments with the two most toxic
      agents in terms of protein damage (guanidine and guanidinopropionic acid) were
      carried out. The effect of the hemodialysis procedure on protein damage was
      evaluated. For investigating also the consequences of these alterations, human
      albumin was treated in vitro to produce an increase in deamidated/isomerized Asx
      residues, and the effects of albumin deamidation on protein binding were
      evaluated. Among the uremic toxins that are able to elicit protein damage,
      guanidine produced a dose-dependent increase in protein damage. No difference was
      found after a hemodialysis session. Deamidated albumin shows normal binding
      capacity to warfarin, salicylic acid, or diazepam but reduced binding to
      homocysteine. In conclusion, uremic toxins, especially guanidine, display an
      ability to induce significant protein damage, which can in turn have functional
      consequences.

PMID- 15466282
TI  - Need to intervene in established acute renal failure.

PMID- 15466283
TI  - Immunosuppression and teratology: evolving guidelines.

PMID- 15466284
TI  - Advancing nephrology around the globe: an invitation to contribute.

PMID- 15466285
TI  - Mitochondrial genome variation in eastern Asia and the peopling of Japan.
AB  - To construct an East Asia mitochondrial DNA (mtDNA) phylogeny, we sequenced the
      complete mitochondrial genomes of 672 Japanese individuals
      (http://www.giib.or.jp/mtsnp/index_e.html). This allowed us to perform a
      phylogenetic analysis with a pool of 942 Asiatic sequences. New clades and
      subclades emerged from the Japanese data. On the basis of this unequivocal
      phylogeny, we classified 4713 Asian partial mitochondrial sequences, with <10%
      ambiguity. Applying population and phylogeographic methods, we used these
      sequences to shed light on the controversial issue of the peopling of Japan.
      Population-based comparisons confirmed that present-day Japanese have their
      closest genetic affinity to northern Asian populations, especially to Koreans,
      which finding is congruent with the proposed Continental gene flow to Japan after
      the Yayoi period. This phylogeographic approach unraveled a high degree of
      differentiation in Paleolithic Japanese. Ancient southern and northern migrations
      were detected based on the existence of basic M and N lineages in Ryukyuans and
      Ainu. Direct connections with Tibet, parallel to those found for the Y
      chromosome, were also apparent. Furthermore, the highest diversity found in Japan
      for some derived clades suggests that Japan could be included in an area of
      migratory expansion to Continental Asia. All the theories that have been proposed
      up to now to explain the peopling of Japan seem insufficient to accommodate fully
      this complex picture.

PMID- 15466286
TI  - Inverted repeat structure of the human genome: the X-chromosome contains a
      preponderance of large, highly homologous inverted repeats that contain testes
      genes.
AB  - We have performed the first genome-wide analysis of the Inverted Repeat (IR)
      structure in the human genome, using a novel and efficient software package
      called Inverted Repeats Finder (IRF). After masking of known repetitive elements,
      IRF detected 22,624 human IRs characterized by arm size from 25 bp to >100 kb
      with at least 75% identity, and spacer length up to 100 kb. This analysis
      required 6 h on a desktop PC. In all, 166 IRs had arm lengths >8 kb. From this
      set, IRs were excluded if they were in unfinished/unassembled regions of the
      genome, or clustered with other closely related IRs, yielding a set of 96 large
      IRs. Of these, 24 (25%) occurred on the X-chromosome, although it represents only
      approximately 5% of the genome. Of the X-chromosome IRs, 83.3% were >/=99%
      identical, compared with 28.8% of autosomal IRs. Eleven IRs from Chromosome X,
      one from Chromosome 11, and seven already described from Chromosome Y contain
      genes predominantly expressed in testis. PCR analysis of eight of these IRs
      correctly amplified the corresponding region in the human genome, and six were
      also confirmed in gorilla or chimpanzee genomes. Similarity dot-plots revealed
      that 22 IRs contained further secondary homologous structures partially
      categorized into three distinct patterns. The prevalence of large highly
      homologous IRs containing testes genes on the X- and Y-chromosomes suggests a
      possible role in male germ-line gene expression and/or maintaining sequence
      integrity by gene conversion.

PMID- 15466287
TI  - Divergence of spatial gene expression profiles following species-specific gene
      duplications in human and mouse.
AB  - To examine the process by which duplicated genes diverge in function, we studied
      how the gene expression profiles of orthologous gene sets in human and mouse are
      affected by the presence of additional recent species-specific paralogs. Gene
      expression profiles were compared across 16 homologous tissues in human and mouse
      using microarray data from the Gene Expression Atlas for 1575 sets of orthologs
      including 250 with species-specific paralogs. We find that orthologs that have
      undergone recent duplication are less likely to have strongly correlated
      expression profiles than those that remain in a one-to-one relationship between
      human and mouse. There is a general trend for paralogous genes to become more
      specialized in their expression patterns, with decreased breadth and increased
      specificity of expression as gene family size increases. Despite this trend,
      detailed examination of some particular gene families where species-specific
      duplications have occurred indicated several examples of apparent
      neofunctionalization of duplicated genes, but only one case of
      subfunctionalization. Often, the expression of both copies of a duplicated gene
      appears to have changed relative to the ancestral state. Our results suggest that
      gene expression profiles are surprisingly labile and that expression in a
      particular tissue may be gained or lost repeatedly during the evolution of even
      small gene families. We conclude that gene duplication is a major driving force
      behind the emergence of divergent gene expression patterns.

PMID- 15466288
TI  - Genetic and haplotype diversity among wild-derived mouse inbred strains.
AB  - With the completion of the mouse genome sequence, it is possible to define the
      amount, type, and organization of the genetic variation in this species. Recent
      reports have provided an overview of the structure of genetic variation among
      classical laboratory mice. On the other hand, little is known about the structure
      of genetic variation among wild-derived strains with the exception of the
      presence of higher levels of diversity. We have estimated the sequence diversity
      due to substitutions and insertions/deletions among 20 inbred strains of Mus
      musculus, chosen to enable interpretation of the molecular variation within a
      clear evolutionary framework. Here, we show that the level of sequence diversity
      present among these strains is one to two orders of magnitude higher than the
      level of sequence diversity observed in the human population, and only a minor
      fraction of the sequence differences observed is found among classical laboratory
      strains. Our analyses also demonstrate that deletions are significantly more
      frequent than insertions. We estimate that 50% of the total variation identified
      in M. musculus may be recovered in intrasubspecific crosses. Alleles at variants
      positions can be classified into 164 strain distribution patterns, a number
      exceeding those reported and predicted in panels of classical inbred strains. The
      number of strains, the analysis of multiple loci scattered across the genome, and
      the mosaic nature of the genome in hybrid and classical strains contribute to the
      observed diversity of strain distribution patterns. However, phylogenetic
      analyses demonstrate that ancient polymorphisms that segregate across species and
      subspecies play a major role in the generation of strain distribution patterns.

PMID- 15466289
TI  - Close split of sorghum and maize genome progenitors.
AB  - It is generally believed that maize (Zea mays L. ssp. mays) arose as a
      tetraploid; however, the two progenitor genomes cannot be unequivocally traced
      within the genome of modern maize. We have taken a new approach to investigate
      the origin of the maize genome. We isolated and sequenced large genomic fragments
      from the regions surrounding five duplicated loci from the maize genome and their
      orthologous loci in sorghum, and then we compared these sequences with the
      orthologous regions in the rice genome. Within the studied segments, we
      identified 11 genes that were conserved in location, order, and orientation. We
      performed phylogenetic and distance analyses and examined the patterns of
      estimated times of divergence for sorghum and maize gene orthologs and also the
      time of divergence for maize orthologs. Our results support a tetraploid origin
      of maize. This analysis also indicates contemporaneous divergence of the
      ancestral sorghum genome and the two maize progenitor genomes about 11.9 million
      years ago (Mya). On the basis of a putative conversion event detected for one of
      the genes, tetraploidization must have occurred before 4.8 Mya, and therefore,
      preceded the major maize genome expansion by gene amplification and
      retrotransposition.

PMID- 15466290
TI  - Gene loss and movement in the maize genome.
AB  - Maize (Zea mays L. ssp. mays), one of the most important agricultural crops in
      the world, originated by hybridization of two closely related progenitors. To
      investigate the fate of its genes after tetraploidization, we analyzed the
      sequence of five duplicated regions from different chromosomal locations. We also
      compared corresponding regions from sorghum and rice, two important crops that
      have largely collinear maps with maize. The split of sorghum and maize
      progenitors was recently estimated to be 11.9 Mya, whereas rice diverged from the
      common ancestor of maize and sorghum approximately 50 Mya. A data set of roughly
      4 Mb yielded 206 predicted genes from the three species, excluding any transposon
      related genes, but including eight gene remnants. On average, 14% of the genes
      within the aligned regions are noncollinear between any two species. However,
      scoring each maize region separately, the set of noncollinear genes between all
      four regions jumps to 68%. This is largely because at least 50% of the duplicated
      genes from the two progenitors of maize have been lost over a very short period
      of time, possibly as short as 5 million years. Using the nearly completed rice
      sequence, we found noncollinear genes in other chromosomal positions, frequently
      in more than one. This demonstrates that many genes in these species have moved
      to new chromosomal locations in the last 50 million years or less, most as single
      gene events that did not dramatically alter gene structure.

PMID- 15466292
TI  - Quantification of multiple gene expression in individual cells.
AB  - Quantitative gene expression analysis aims to define the gene expression patterns
      determining cell behavior. So far, these assessments can only be performed at the
      population level. Therefore, they determine the average gene expression within a
      population, overlooking possible cell-to-cell heterogeneity that could lead to
      different cell behaviors/cell fates. Understanding individual cell behavior
      requires multiple gene expression analyses of single cells, and may be
      fundamental for the understanding of all types of biological events and/or
      differentiation processes. We here describe a new reverse transcription
      polymerase chain reaction (RT-PCR) approach allowing the simultaneous
      quantification of the expression of 20 genes in the same single cell. This method
      has broad application, in different species and any type of gene combination. RT
      efficiency is evaluated. Uniform and maximized amplification conditions for all
      genes are provided. Abundance relationships are maintained, allowing the precise
      quantification of the absolute number of mRNA molecules per cell, ranging from 2
      to 1.28 x 10(9) for each individual gene. We evaluated the impact of this
      approach on functional genetic read-outs by studying an apparently homogeneous
      population (monoclonal T cells recovered 4 d after antigen stimulation), using
      either this method or conventional real-time RT-PCR. Single-cell studies revealed
      considerable cell-to-cell variation: All T cells did not express all individual
      genes. Gene coexpression patterns were very heterogeneous. mRNA copy numbers
      varied between different transcripts and in different cells. As a consequence,
      this single-cell assay introduces new and fundamental information regarding
      functional genomic read-outs. By comparison, we also show that conventional
      quantitative assays determining population averages supply insufficient
      information, and may even be highly misleading.

PMID- 15466293
TI  - High-content screening microscopy identifies novel proteins with a putative role
      in secretory membrane traffic.
AB  - Here we describe the establishment of microscope-based functional screening
      assays in intact cells that allow us to systematically identify new proteins
      involved in secretory membrane traffic, and proteins that can influence the
      integrity of the Golgi complex. We were able to identify 20 new proteins that
      affected either secretory transport, Golgi morphology, or both, when
      overexpressed in cells. Control experiments with human orthologs to yeast
      proteins with a role in membrane traffic, or already well characterized mammalian
      regulators of the secretory pathway, confirmed the specificity and significance
      of our results. Proteins localized to the Golgi complex or endoplasmic reticulum
      (ER) showed preferential interference in our assays. Bioinformatic analysis of
      the new proteins interfering with membrane traffic and/or Golgi integrity
      revealed broad functional variety, but demonstrated a bias towards proteins with
      predicted coiled-coil domains and repeat structures. Extending our approach to a
      much larger set of novel proteins in the future will be an important step toward
      a more comprehensive understanding of the molecular basis of the secretory
      pathway. It will also serve as an example for similar microscope-based screens
      addressing different biological questions.

PMID- 15466294
TI  - Predicting subcellular localization via protein motif co-occurrence.
AB  - The prediction of subcellular localization of proteins from their primary
      sequence is a challenging problem in bioinformatics. We have created a Bayesian
      network localization predictor called PSLT that is based on the combinatorial
      presence of InterPro motifs and specific membrane domains in human proteins. This
      probabilistic framework generates a likelihood of localization to all organelles
      and allows to predict multicompartmental proteins. When used to predict on nine
      compartments, PSLT achieves an accuracy of 78% as estimated by using a 10-fold
      cross-validation test and a coverage of 74%. When used to predict the
      localization of proteins from other closely related species, it achieves a
      prediction accuracy and a coverage >80%. We compared the localization predictions
      of PSLT to those determined through GFP-tagging and microscopy for a group of
      human proteins. We found two general classes of proteins that are mislocalized by
      the GFP-tagging strategy but are correctly localized by PSLT. This suggests that
      PSLT can be used in combination with experimental approaches for localization to
      identify proteins for which additional experimental validation is required. We
      used our predictor to annotate all 9793 human proteins from SWISS-PROT release
      41.25, 16% of which are predicted by PSLT to be present in more than one
      compartment.

PMID- 15466295
TI  - Decoding human regulatory circuits.
AB  - Clusters of transcription factor binding sites (TFBSs) which direct gene
      expression constitute cis-regulatory modules (CRMs). We present a novel
      algorithm, based on Gibbs sampling, which locates, de novo, the cis features of
      these CRMs, their component TFBSs, and the properties of their spatial
      distribution. The algorithm finds 69% of experimentally reported TFBSs and 85% of
      the CRMs in a reference data set of regions upstream of genes differentially
      expressed in skeletal muscle cells. A discriminant procedure based on the output
      of the model specifically discriminated regulatory sequences in muscle-specific
      genes in an independent test set. Application of the method to the analysis of
      2710 10-kb fragments upstream of annotated human genes identified 17 novel
      candidate modules with a false discovery rate </=0.05, demonstrating the
      applicability of the method to genome-scale data.

PMID- 15466296
TI  - Large-scale mutagenesis of the yeast genome using a Tn7-derived multipurpose
      transposon.
AB  - We present here an unbiased and extremely versatile insertional library of yeast
      genomic DNA generated by in vitro mutagenesis with a multipurpose element derived
      from the bacterial transposon Tn7. This mini-Tn7 element has been engineered such
      that a single insertion can be used to generate a lacZ fusion, gene disruption,
      and epitope-tagged gene product. Using this transposon, we generated a plasmid
      based library of approximately 300,000 mutant alleles; by high-throughput
      screening in yeast, we identified and sequenced 9032 insertions affecting 2613
      genes (45% of the genome). From analysis of 7176 insertions, we found little bias
      in Tn7 target-site selection in vitro. In contrast, we also sequenced 10,174 Tn3
      insertions and found a markedly stronger preference for an AT-rich 5-base pair
      target sequence. We further screened 1327 insertion alleles in yeast for
      hypersensitivity to the chemotherapeutic cisplatin. Fifty-one genes were
      identified, including four functionally uncharacterized genes and 25 genes
      involved in DNA repair, replication, transcription, and chromatin structure. In
      total, the collection reported here constitutes the largest plasmid-based set of
      sequenced yeast mutant alleles to date and, as such, should be singularly useful
      for gene and genome-wide functional analysis.

PMID- 15466291
TI  - Characterization of the maize endosperm transcriptome and its comparison to the
      rice genome.
AB  - The cereal endosperm is a major organ of the seed and an important component of
      the world's food supply. To understand the development and physiology of the
      endosperm of cereal seeds, we focused on the identification of genes expressed at
      various times during maize endosperm development. We constructed several cDNA
      libraries to identify full-length clones and subjected them to a twofold
      enrichment. A total of 23,348 high-quality sequence-reads from 5'- and 3'-ends of
      cDNAs were generated and assembled into a unigene set representing 5326 genes
      with paired sequence-reads. Additional sequencing yielded a total of 3160 (59%)
      completely sequenced, full-length cDNAs. From 5326 unigenes, 4139 (78%) can be
      aligned with 5367 predicted rice genes and by taking only the "best hit" be
      mapped to 3108 positions on the rice genome. The 22% unigenes not present in rice
      indicate a rapid change of gene content between rice and maize in only 50 million
      years. Differences in rice and maize gene numbers also suggest that maize has
      lost a large number of duplicated genes following tetraploidization. The larger
      number of gene copies in rice suggests that as many as 30% of its genes arose
      from gene amplification, which would extrapolate to a significant proportion of
      the estimated 44,027 candidate genes of its entire genome. Functional
      classification of the maize endosperm unigene set indicated that more than a
      fourth of the novel functionally assignable genes found in this study are
      involved in carbohydrate metabolism, consistent with its role as a storage organ.

PMID- 15466297
TI  - A comprehensive genetic map of the cattle genome based on 3802 microsatellites.
AB  - A microsatellite-based high-density genetic map facilitates for fine mapping of
      hereditary traits of interest, characterization of meiosis, and providing a
      foundation for physical map construction. Here, we developed a comprehensive
      genetic map on the basis of >880,000 genotypes across the USDA MARC cattle
      reference families with a potential genetic resolution of 0.8 cM at the 95%
      confidence level ( approximately 800 kb in the bovine genome). We incorporated
      2325 microsatellites into the second-generation genetic map by linkage analysis
      based on sex-averaged two-point LOD scores (>3.0), of which 2293 were fine-mapped
      by multipoint linkage analysis. The new 3160-cM map comprised of 29 sex-averaged
      autosomal linkage groups and a sex-specific X-chromosome linkage group includes
      3960 markers with 2389 positions, resulting in an average interval size of 1.4
      cM. More than half (51%) of the total length of the map is covered with intervals
      of 2.0 cM or less, and the largest gap is a 10.2-cM interval on the X-linkage
      group. The new map should accelerate fine mapping and positional cloning of genes
      for genetic diseases and economically important traits in cattle, as well as
      related livestock species, such as sheep and goat.

PMID- 15466298
TI  - Context and behavioral processes in extinction.
AB  - This article provides a selective review and integration of the behavioral
      literature on Pavlovian extinction. The first part reviews evidence that
      extinction does not destroy the original learning, but instead generates new
      learning that is especially context-dependent. The second part examines insights
      provided by research on several related behavioral phenomena (the interference
      paradigms, conditioned inhibition, and inhibition despite reinforcement). The
      final part examines four potential causes of extinction: the discrimination of a
      new reinforcement rate, generalization decrement, response inhibition, and
      violation of a reinforcer expectation. The data are consistent with behavioral
      models that emphasize the role of generalization decrement and expectation
      violation, but would be more so if those models were expanded to better
      accommodate the finding that extinction involves a context-modulated form of
      inhibitory learning.

PMID- 15466299
TI  - Cognitive processes in extinction.
AB  - Human conditioning research shows that learning is closely related to consciously
      available contingency knowledge, requires attentional resources, and is
      influenced by language. This research suggests a cognitive model in which
      extinction consists of changes in contingency beliefs in long-term memory.
      Laboratory and clinical evidence on extinction is briefly reviewed, and it is
      concluded that the evidence supports the cognitive position. There is little
      evidence for a separate, noncognitive conditioning system. The primary
      implication for neural analysis is that learning and extinction are unlikely to
      be reducible to direct connections in which one stimulus simply activates or
      inhibits the memory representation of another. Rather, an adequate neural model
      will involve the integration of both low-level and high-level systems, including
      attention, representation of stimulus relations in long-term memory, and a
      dynamic performance mechanism based on anticipation, not just activation.

PMID- 15466300
TI  - Spontaneous recovery.
AB  - Spontaneous recovery from extinction is one of the most basic phenomena of
      Pavlovian conditioning. Although it can be studied by using a variety of designs,
      some procedures are better than others for identifying the involvement of
      underlying learning processes. A wide range of different learning mechanisms has
      been suggested as being engaged by extinction, most of which have implications
      for the nature of spontaneous recovery. However, despite the centrality of the
      notion of spontaneous recovery to the understanding of extinction, the empirical
      literature on its determinants is relatively sparse and quite mixed. Its very
      ubiquity suggests that spontaneous recovery has multiple sources.

PMID- 15466301
TI  - Facilitation of fear extinction by D-cycloserine: theoretical and clinical
      implications.
AB  - Anxiety disorders are among the most common psychological disturbances in the
      industrialized world. Current behavioral therapy procedures for these disorders
      are somewhat effective, but their efficacy could be substantially improved.
      Because these procedures are largely based on the process of extinction,
      manipulations that enhance extinction may lead to improvements in treatment
      effectiveness. We review the evidence that D-cycloserine (DCS), a partial NMDA
      agonist, facilitates extinction of learned fear in rats. Although only a few
      studies have examined the effects of DCS on extinction of learned fear, this work
      suggests that this drug may have a number of potential clinical benefits. In
      addition, attempts at interpreting this research illustrate our limited
      understanding of the processes involved in extinction.

PMID- 15466302
TI  - Brain mechanisms of extinction of the classically conditioned eyeblink response.
AB  - It is well established that the cerebellum and its associated circuitry are
      essential for classical conditioning of the eyeblink response and other discrete
      motor responses (e.g., limb flexion, head turn, etc.) learned with an aversive
      unconditioned stimulus (US). However, brain mechanisms underlying extinction of
      these responses are still relatively unclear. Behavioral studies have
      demonstrated extinction as an active learning process distinct from acquisition.
      Experimental data in eyeblink conditioning suggest that plastic changes specific
      to extinction may play an important role in this process. Both cerebellar and
      hippocampal systems may be involved in extinction of these memories. The nature
      of this phenomenon and identification of the neural substrates necessary for
      extinction of originally learned responses is the topic of this review.

PMID- 15466303
TI  - Emotional perseveration: an update on prefrontal-amygdala interactions in fear
      extinction.
AB  - Fear extinction refers to the ability to adapt as situations change by learning
      to suppress a previously learned fear. This process involves a gradual reduction
      in the capacity of a fear-conditioned stimulus to elicit fear by presenting the
      conditioned stimulus repeatedly on its own. Fear extinction is context-dependent
      and is generally considered to involve the establishment of inhibitory control of
      the prefrontal cortex over amygdala-based fear processes. In this paper, we
      review research progress on the neural basis of fear extinction with a focus on
      the role of the amygdala and the prefrontal cortex. We evaluate two competing
      hypotheses for how the medial prefrontal cortex inhibits amygdala output. In
      addition, we present new findings showing that lesions of the basal amygdala do
      not affect fear extinction. Based on this result, we propose an updated model for
      integrating hippocampal-based contextual information with prefrontal-amygdala
      circuitry.

PMID- 15466304
TI  - Like extinction, latent inhibition of conditioned fear in mice is blocked by
      systemic inhibition of L-type voltage-gated calcium channels.
AB  - Having recently shown that extinction of conditioned fear depends on L-type
      voltage-gated calcium channels (LVGCCs), we have been seeking other protocols
      that require this unusual induction mechanism. We tested latent inhibition (LI)
      of fear, because LI resembles extinction except that cue exposures precede,
      rather than follow, cue-shock pairing. Systemic injections of two LVGCC
      inhibitors, nifedipine and diltiazem, before pre-exposure blocked LI completely
      with no evidence of state-dependent learning. The results indicate that
      extinction and LI share a common molecular requirement and may support the notion
      that LI, like extinction, is a form of inhibitory learning.

PMID- 15466305
TI  - Postextinction infusion of a mitogen-activated protein kinase inhibitor into the
      medial prefrontal cortex impairs memory of the extinction of conditioned fear.
AB  - We investigated whether postextinction training infusion of PD098059, a selective
      inhibitor of mitogen-activated protein kinase (MAPK) activation, into the medial
      prefrontal cortex, would impair retention of extinction learning in rats. We
      found that immediate, but not late (2 or 4 h), postextinction infusion of
      PD098059 provoked a full return of conditioned freezing. These results suggest
      that activation of prefrontal MAPK in early stages of postextinction training
      participates in processes that protect against spontaneous recovery of aversive
      responses.

PMID- 15466306
TI  - Delayed recall of fear extinction in rats with lesions of ventral medial
      prefrontal cortex.
AB  - Extinction of auditory fear conditioning is thought to form a new memory. We
      previously found that rats with vmPFC lesions could extinguish fear to the tone
      within a session, but showed no recall of extinction 24 h later. One
      interpretation is that the vmPFC is the sole storage site of extinction memory.
      However, it is also possible that lesioned rats were unable to retrieve
      extinction memory stored in other structures. To determine if a latent extinction
      memory could be retrieved with additional training, we repeated the experiment
      but added an additional 5 d of extinction reminder trials. Replicating our
      previous findings, vmPFC-lesioned rats extinguished normally on day 1, but showed
      no recall of extinction on day 2. Over the next 5 d, however, lesioned rats
      showed significant savings in their rate of re-extinction. Thus, the vmPFC is not
      the only site where extinction memory is stored. Nevertheless, lesioned rats
      receiving only two extinction trials per day required twice as many days to
      initiate extinction as controls. Although recall of extinction is possible
      without the vmPFC, it is significantly delayed. We suggest that the vmPFC
      accelerates extinction by permitting access to recently learned extinction
      trials, thereby maximizing behavioral flexibility.

PMID- 15466307
TI  - Reinstatement of extinguished conditioned responses and negative stimulus valence
      as a pathway to return of fear in humans.
AB  - The present study investigated reinstatement of conditioned responses in humans
      by using a differential Pavlovian conditioning procedure. Evidence for
      reinstatement was established in a direct (fear rating) and in an indirect
      measure (secondary reaction time task) of conditioning. Moreover, the amount of
      reinstatement in the secondary reaction time task was significantly correlated
      with the difference in valence between the conditioned stimulus (CS)+ and the CS
      after extinction. These data provide clear evidence for reinstatement and for the
      role of negative stimulus valence in the return of conditioned responding after
      extinction.

PMID- 15466308
TI  - Generalization of extinguished skin conductance responding in human fear
      conditioning.
AB  - In a human fear conditioning paradigm using the skin conductance response (SCR),
      participants were assigned to two groups. Following identical acquisition, group
      ABA (n = 16) was extinguished to a generalization stimulus (GS), whereas group
      AAB (n = 20) was extinguished to the conditioned stimulus (CS). At test,
      presenting the CS in group ABA yielded a strongly recovered SCR. Presenting the
      GS in group AAB, on the other hand, did not disrupt the effects of extinction. We
      conclude that extinguishing the CS (group AAB) is an efficient strategy to
      overcome the stimulus specificity of extinction observed otherwise (group ABA).
      Clinical implications are discussed.

PMID- 15466309
TI  - Reversal of motor learning in the vestibulo-ocular reflex in the absence of
      visual input.
AB  - Motor learning in the vestibulo-ocular reflex (VOR) and eyeblink conditioning use
      similar neural circuitry, and they may use similar cellular plasticity
      mechanisms. Classically conditioned eyeblink responses undergo extinction after
      prolonged exposure to the conditioned stimulus in the absence of the
      unconditioned stimulus. We investigated the possibility that a process similar to
      extinction may reverse learned changes in the VOR. We induced a learned
      alteration of the VOR response in rhesus monkeys using magnifying or
      miniaturizing goggles, which caused head movements to be accompanied by visual
      image motion. After learning, head movements in the absence of visual stimulation
      caused a loss of the learned eye movement response. When the learned gain was
      low, this reversal of learning occurred only when head movements were delivered,
      and not when the head was held stationary in the absence of visual input,
      suggesting that this reversal is mediated by an active, extinction-like process.

PMID- 15466310
TI  - Extinction as new learning versus unlearning: considerations from a computer
      simulation of the cerebellum.
AB  - Like many forms of Pavlovian conditioning, eyelid conditioning displays robust
      extinction. We used a computer simulation of the cerebellum as a tool to consider
      the widely accepted view that extinction involves new, inhibitory learning rather
      than unlearning of acquisition. Previously, this simulation suggested basic
      mechanistic features of extinction and savings in eyelid conditioning, with
      predictions born out by experiments. We review previous work showing that the
      simulation reproduces behavioral phenomena and lesion effects generally taken as
      evidence that extinction does not reverse acquisition, even though its plasticity
      is bidirectional with no site dedicated to inhibitory learning per se. In
      contrast, we show that even though the sites of plasticity are, in general,
      affected in opposite directions by acquisition and extinction training, most
      synapses do not return to their naive state after acquisition followed by
      extinction. These results suggest caution in interpreting a range of observations
      as necessarily supporting extinction as unlearning or extinction as new
      inhibitory learning. We argue that the question "is extinction reversal of
      acquisition or new inhibitory learning?" is therefore not well posed because the
      answer may depend on factors such as the brain system in question or the level of
      analysis considered.

PMID- 15466312
TI  - Mismatch between what is expected and what actually occurs triggers memory
      reconsolidation or extinction.
AB  - In previous experiments on contextual memory, we proposed that the unreinforced
      re-exposure to the learning context (conditioned stimulus, CS) acts as a switch
      guiding the memory course toward reconsolidation or extinction, depending on
      reminder duration. This proposal implies that the system computes the total
      exposure time to the context, from CS onset to CS offset, and therefore, that the
      reminder presentation must be terminated for the switching mechanism to become
      operative. Here we investigated to what extent this requirement is necessary, and
      we explored the relation between diverse phases in the reconsolidation and
      extinction processes. We used the contextual memory model of the crab
      Chasmagnathus which involves an association between the learning context (CS) and
      a visual danger stimulus (unconditioned stimulus, US). Administration of
      cycloheximide was used to test the lability state of memory at different time
      points. The results show that two factors, no-reinforcement during the reminder
      (i.e., CS re-exposure) and CS offset are the necessary conditions for both
      processes to occur. Regardless of the reminder duration, memory retrieved by
      unreinforced CS re-exposure emerges intact and consolidated when tested before CS
      offset, suggesting that neither reconsolidation nor extinction is concomitant
      with CS re-exposure. Either process could only be triggered once the definitive
      mismatch between CS and US is confirmed by CS termination without the expected
      reinforcement.

PMID- 15466311
TI  - Retrieval does not induce reconsolidation of inhibitory avoidance memory.
AB  - It has been suggested that retrieval during a nonreinforced test induces
      reconsolidation instead of extinction of the mnemonic trace. Reconsolidation
      would preserve the original memory from the labilization induced by its
      nonreinforced recall through a hitherto uncharacterized mechanism requiring
      protein synthesis. Given the importance that such a process would have in terms
      of maintaining, as part of the animal behavioral repertoire, a learned response
      that has been devalued by experience, we analyzed its existence for the memory
      associated with a one-trial, step-down inhibitory avoidance task (IA), a memory
      whose consolidation and extinction require protein synthesis in the CA1 region of
      the dorsal hippocampus (CA1) and involve the participation of the basolateral
      amygdala (BLA) and entorhinal cortex (ENT). Rats were trained in IA, and 24 h
      later they were submitted either to a pure reactivation session (retrieval
      without stepping down), which was unable by itself to initiate extinction of the
      avoidance response, or to a second training session. Fifteen minutes before or 3
      h after either the reactivation or the retraining sessions, animals were infused
      with the protein synthesis inhibitor anisomycin (ANI) into CA1, BLA, or ENT.
      Contrary to the prediction of the reconsolidation hypothesis, none of these
      treatments affected subsequent memory retention. Because reconsolidation is
      regarded to be a direct consequence of retrieval, one would expect that, when
      given before a retention test or a pure reactivation session, enhancers of memory
      expression should permanently improve retention and, therefore, facilitate
      retrieval both in that and in subsequent sessions. Using two well-known retrieval
      enhancers, noradrenaline and adrenocorticotropin(1-24), we could not find any
      evidence suggestive of reconsolidation. Hence, our results indicate that there is
      no retrieval-induced, protein synthesis-dependent process that would cause
      reconsolidation of IA memory.

PMID- 15466313
TI  - Spontaneous recovery after extinction of the conditioned proboscis extension
      response in the honeybee.
AB  - In honeybees, the proboscis extension response (PER) can be conditioned by
      associating an odor stimulus (CS) to a sucrose reward (US). Conditioned responses
      to the CS, which are acquired by most bees after a single CS-US pairing,
      disappear after repeated unrewarded presentations of the CS, a process called
      extinction. Extinction is usually thought to be based either on (1) the
      disruption of the stored CS-US association, or (2) the formation of an inhibitory
      "CS-no US" association that is better retrieved than the initial CS-US
      association. The observation of spontaneous recovery, i.e., the reappearance of
      responses to the CS after time passes following extinction, is traditionally
      interpreted as a proof for the formation of a transient inhibitory association.
      To provide a better understanding of extinction in honeybees, we examined whether
      time intervals during training and extinction or the number of conditioning and
      extinction trials have an effect on the occurrence of spontaneous recovery. We
      found that spontaneous recovery mostly occurs when conditioning and testing took
      place in a massed fashion (1-min intertrial intervals). Moreover, spontaneous
      recovery depended on the time elapsed since extinction, 1 h being an optimum.
      Increasing the number of conditioning trials improved the spontaneous recovery
      level, whereas increasing the number of extinction trials reduced it. Lastly, we
      show that after single-trial conditioning, spontaneous recovery appears only once
      after extinction. These elements suggest that in honeybees extinction of the PER
      actually reflects the impairment of the CS-US association, but that depending on
      training parameters different memory substrates are affected.

PMID- 15466314
TI  - Factors regulating the effects of hippocampal inactivation on renewal of
      conditional fear after extinction.
AB  - After extinction of fear to a Pavlovian conditional stimulus (CS), contextual
      stimuli come to regulate the expression of fear to that CS. There is growing
      evidence that the context dependence of memory retrieval after extinction
      involves the hippocampus. In the present experiment, we examine whether
      hippocampal involvement in memory retrieval after extinction is related to the
      history of CS presentations in the context used for retrieval testing. We used
      infusions of muscimol to inactivate the dorsal hippocampus (DH) during
      postextinction retrieval tests that were conducted in contexts that differed in
      their history of CS presentations in that context. We found that DH inactivation
      affected the context-dependent retrieval of extinction (i.e., renewal) when
      testing occurred in a context that had no history of CS exposure, but not in a
      context that reliably predicted the CS. These results are discussed in terms of
      theories regarding the role of the hippocampus in contextual memory retrieval.

PMID- 15466315
TI  - Inactivation of the anterior cingulate cortex impairs extinction of rabbit jaw
      movement conditioning and prevents extinction-related inhibition of hippocampal
      activity.
AB  - Although past research has highlighted the involvement of limbic structures such
      as the anterior cingulate cortex (ACC) and hippocampus in learning, few have
      addressed the nature of their interaction. The current study of rabbit jaw
      movement conditioning used a combination of reversible lesions and
      electrophysiology to examine the involvement of the hippocampus and the ACC
      during acquisition, performance, and extinction. We found that microinfusions of
      procaine into the ACC did not significantly alter the rate of behavioral learning
      or the amplitude of hippocampal conditioned unit responses, but that they
      disrupted the rhythmic periodicity of conditioned jaw movements. During
      extinction, whereas controls showed a rapid decline in behavioral CRs and active
      inhibition of hippocampal unit responses, ACC lesioned rabbits showed a
      persistence of conditioning-related hippocampal activity and behavioral
      responding. The results show that the ACC can be important for adaptive
      suppression of conditioned behavior and suggest a crucial physiological
      modulation of hippocampus by ACC during extinction.

PMID- 15466316
TI  - Lesions of rat infralimbic cortex enhance recovery and reinstatement of an
      appetitive Pavlovian response.
AB  - The prefrontal cortex (PFC) has a well-established role in the inhibition of
      inappropriate responding, and evidence suggests that the infralimbic (IL) region
      of the rat medial PFC (MPFC) may be involved in some aspects of extinction of
      conditioned fear. MPFC lesions including, but not those sparing the IL cortex
      increase spontaneous recovery of extinguished conditioned fear when tested 24 h
      after an initial extinction session. The current experiment extended these
      findings by use of appetitive rather than aversive conditioning. Ten IL-lesioned
      and 11 sham-operated rats were trained on a Pavlovian task in which a conditioned
      stimulus (CS) was followed by food pellets (the unconditioned stimulus or US). IL
      lesions had no effect on extinction of the conditioned response (CR, magazine
      entries) during the first extinction session. However, the level of spontaneous
      recovery between the first extinction session and a second, 24 h later, was
      increased in IL-lesioned rats relative to sham animals. In contrast, evidence of
      savings measured between the extinction sessions did not differ between groups.
      Furthermore, reinstatement of the CR following unsignaled delivery of the US was
      also increased in IL-lesioned rats.

PMID- 15466317
TI  - An egr-1 (zif268) antisense oligodeoxynucleotide infused into the amygdala
      disrupts fear conditioning.
AB  - Studies of gene expression following fear conditioning have demonstrated that the
      inducible transcription factor, egr-1, is increased in the lateral nucleus of the
      amygdala shortly following fear conditioning. These studies suggest that egr-1
      and its protein product Egr-1 in the amygdala are important for learning and
      memory of fear. To directly test this hypothesis, an egr-1 antisense
      oligodeoxynucleotide (antisense-ODN) was injected bilaterally into the amygdala
      prior to contextual fear conditioning. The antisense-ODN reduced Egr-1 protein in
      the amygdala and interfered with fear conditioning. A 250-pmole dose produced an
      11% decrease in Egr-1 protein and reduced long-term memory of fear as measured by
      freezing in a retention test 24 h after conditioning, but left shock-induced
      freezing intact. A larger 500-pmole dose produced a 25% reduction in Egr-1
      protein and significantly decreased both freezing immediately following
      conditioning and freezing in the retention test. A nonsense-ODN had no effect on
      postshock or retention test freezing. In addition, 500 pmole of antisense-ODN
      infused prior to the retention test in previously trained rats did not reduce
      freezing, indicating that antisense-ODN did not suppress conditioned fear
      behavior. Finally, rats infused with 500 pmole of antisense-ODN displayed
      unconditioned fear to a predator odor, demonstrating that unconditioned freezing
      was unaffected by the antisense-ODN. The data indicate that the egr-1 antisense
      ODN interferes with learning and memory processes of fear without affecting
      freezing behavior and suggests that the inducible transcription factor Egr-1
      within the amygdala plays important functions in long-term learning and memory of
      fear.

PMID- 15466318
TI  - CB1 cannabinoid receptors modulate kinase and phosphatase activity during
      extinction of conditioned fear in mice.
AB  - Cannabinoid receptors type 1 (CB1) play a central role in both short-term and
      long-term extinction of auditory-cued fear memory. The molecular mechanisms
      underlying this function remain to be clarified. Several studies indicated
      extracellular signal-regulated kinases (ERKs), the phosphatidylinositol 3-kinase
      with its downstream effector AKT, and the phosphatase calcineurin as potential
      molecular substrates of extinction behavior. To test the involvement of these
      kinase and phosphatase activities in CB1-dependent extinction of conditioned fear
      behavior, conditioned CB1-deficient mice (CB1(-/-)) and wild-type littermates
      (CB1(+/+)) were sacrificed 30 min after recall of fear memory, and activation of
      ERKs, AKT, and calcineurin was examined by Western blot analysis in different
      brain regions. As compared with CB1(+/+), the nonreinforced tone presentation 24
      h after auditory-cued fear conditioning led to lower levels of phosphorylated
      ERKs and/or calcineurin in the basolateral amygdala complex, ventromedial
      prefrontal cortex, dorsal hippocampus, and ventral hippocampus of CB1(-/-). In
      contrast, higher levels of phosphorylated p44 ERK and calcineurin were observed
      in the central nucleus of the amygdala of CB1(-/-). Phosphorylation of AKT was
      more pronounced in the basolateral amygdala complex and the dorsal hippocampus of
      CB1(-/-). We propose that the endogenous cannabinoid system modulates extinction
      of aversive memories, at least in part via regulation of the activity of kinases
      and phosphatases in a brain structure-dependent manner.

PMID- 15466319
TI  - Extinction memory improvement by the metabolic enhancer methylene blue.
AB  - We investigated whether postextinction administration of methylene blue (MB)
      could enhance retention of an extinguished conditioned response. MB is a redox
      compound that at low doses elevates cytochrome oxidase activity, thereby
      improving brain energy production. Saline or MB (4 mg/kg intraperitoneally) were
      administered to rats for 5 d following extinction training of tone-footshock
      conditioning. Postextinction freezing was lower in rats receiving MB compared
      with saline, suggesting that MB improved retention of the extinction memory. The
      MB effect was specific to tone-evoked freezing because there were no differences
      in pretone freezing. Control subjects similarly injected with MB showed no
      evidence of nonspecific effects on measures of motor activity and fearfulness. MB
      treated rats exhibited both greater retention of extinction and greater overall
      brain metabolic activity. Rats with higher retention of extinction also showed a
      relative increase in cytochrome oxidase activity in prefrontal cortical regions,
      especially anterior infralimbic cortex, dorsal and medial frontal cortex, and
      lateral orbital cortex. These regional metabolic increases were also correlated
      to the behavioral freezing index used to assess retention of extinction. It was
      concluded that MB administered postextinction could enhance retention of
      extinction memory through an increase in brain cytochrome oxidase activity.

PMID- 15466320
TI  - Facilitation of memory for extinction of drug-induced conditioned reward: role of
      amygdala and acetylcholine.
AB  - These experiments examined the effects of posttrial peripheral and intra-amygdala
      injections of the cholinergic muscarinic receptor agonist oxotremorine on memory
      consolidation underlying extinction of amphetamine conditioned place preference
      (CPP) behavior. Male Long-Evans rats were initially trained and tested for an
      amphetamine (2 mg/kg) CPP. Rats were subsequently given limited extinction
      training, followed by immediate posttrial peripheral or intrabasolateral amygdala
      injections of oxotremorine. A second CPP test was then administered, and the
      amount of time spent in the previously amphetamine-paired and saline-paired
      apparatus compartments was recorded. Peripheral (0.07 or 0.01 mg/kg) or intra
      amygdala (10 etag/0.5 microL) postextinction trial injections of oxotremorine
      facilitated CPP extinction. Oxotremorine injections that were delayed 2 h
      posttrial training did not enhance CPP extinction, indicating a time-dependent
      effect of the drug on memory consolidation processes. The findings indicate that
      memory consolidation for extinction of approach behavior to environmental stimuli
      previously paired with drug reward can be facilitated by posttrial peripheral or
      intrabasolateral amygdala administration of a cholinergic agonist.

PMID- 15466322
TI  - Diffusion-weighted imaging parameters to track success of pyogenic brain abscess
      therapy.

PMID- 15466321
TI  - Extinction training regulates neuroadaptive responses to withdrawal from chronic
      cocaine self-administration.
AB  - Cocaine produces multiple neuroadaptations with chronic repeated use. Many of
      these neuroadaptations can be reversed or normalized by extinction training
      during withdrawal from chronic cocaine self-administration in rats. This article
      reviews our past and present studies on extinction-induced modulation of the
      neuroadaptive response to chronic cocaine in the mesolimbic dopamine system, and
      the role of this modulation in addictive behavior in rats. Extinction training
      normalizes tyrosine hydroxylase levels in the nucleus accumbens (NAc) shell, an
      effect that could help ameliorate dysphoria and depression associated with
      withdrawal from chronic cocaine use. Extinction training also increases levels of
      GluR1 and GluR2/3 AMPA receptor subunits, while normalizing deficits in NR1 NMDA
      receptor subunits, in a manner consistent with long-term potentiation of
      excitatory synapses in the NAc shell. Our results suggest that extinction-induced
      increases in AMPA and NMDA receptors may restore deficits in cortico-accumbal
      neurotransmission in the NAc shell and facilitate inhibitory control over cocaine
      seeking behavior. Other changes identified by gene expression profiling,
      including up-regulation in the AMPA receptor aggregating protein Narp, suggest
      that extinction training induces extensive synaptic reorganization. These studies
      highlight potential benefits for extinction training procedures in the treatment
      of drug addiction.

PMID- 15466323
TI  - Stroke wars: episode IV CT strikes back.

PMID- 15466324
TI  - Diffusion-weighted imaging in the assessment of brain abscesses therapy.
AB  - BACKGROUND AND PURPOSE: Surgically or conservatively treated brain abscesses may
      resolve, or pus may re-accumulate, requiring further intervention or treatment
      change. We hypothesized that diffusion-weighted (DW) imaging is useful in
      depicting features of abscesses related to therapeutic success or failure.
      METHODS: Conventional contrast-enhanced T1- and T2-weighted imaging and DW
      imaging were performed in seven patients (aged 30-69 years) with proved pyogenic
      brain abscesses. The center of the abscess was qualitatively and quantitatively
      analyzed at initial and follow-up imaging in all patients. We correlated the
      signal intensity on trace DW images and the apparent diffusion coefficients
      (ADCs) with the clinical and laboratory data, particularly with respect to
      treatment failure and repeat therapy. RESULTS: Surgical drainage was performed in
      six patients; one patient was treated with only antibiotics. All abscess cavities
      initially had high signal intensity (restricted diffusion) on DW images, with a
      mean ADC value of 0.52 x 10 (-3)mm (2)/s. Low signal intensity at DW imaging with
      high ADC were seen on follow-up images in the patient receiving medication and in
      four patients in whom the abscesses were drained; this correlated with a good
      therapeutic response. Two patients underwent drainage; their second follow-up DW
      images showed areas of high signal intensity and low ADC values suggesting re
      accumulation of pus. Increased C-reactive protein level and WBC count correlated
      well with DW image findings. CONCLUSION: DW imaging was superior to conventional
      MR imaging in evaluating the success or failure of abscess therapy. Restricted
      diffusion in a drained abscess corresponded to pus.

PMID- 15466325
TI  - Method for combining information from white matter fiber tracking and gray matter
      parcellation.
AB  - We introduce a method for combining fiber tracking from diffusion-tensor (DT)
      imaging with cortical gray matter parcellation from structural high-spatial
      resolution 3D spoiled gradient-recalled acquisition in the steady state images.
      We applied this method to a tumor case to determine the impact of the tumor on
      white matter architecture. We conclude that this new method for combining
      structural and DT imaging data is useful for understanding cortical connectivity
      and the localization of fiber tracts and their relationship with cortical anatomy
      and brain abnormalities.

PMID- 15466327
TI  - Diffusion-weighted MR imaging in acute ischemia: value of apparent diffusion
      coefficient and signal intensity thresholds in predicting tissue at risk and
      final infarct size.
AB  - BACKGROUND AND PURPOSE: Identifying tissue at risk for infarction is an important
      goal of stroke imaging. This study was performed to determine whether pixel-based
      apparent diffusion coefficient (ADC) and signal intensity ratio are helpful
      diffusion-weighted (DW) imaging metrics to predict tissue at risk for infarction.
      METHODS: Twelve patients presenting with acute hemispheric strokes underwent DW
      imaging within 7 hours of symptom onset. Region of interest (ROI), pixel-based
      ADC, and signal intensity analyses were performed at initial DW imaging to assess
      area of infarct growth, final infarct area, and normal tissue. RESULTS: Pixel
      based analysis was less accurate than ROI-based analysis for evaluating infarct
      growth or final infarct with ADC, ADC ratio, and signal intensity ratios. In
      pixel-based analysis, signal intensity ratios were better than ADCs or ADC ratios
      for identifying tissue at risk (accuracy, 67.4%) and for predicting final infarct
      (accuracy, 79.9%). Linear regression analysis demonstrated a strong correlation
      between lesion volume on quantitative DW images or ADC maps and final infarct
      volume (P < .001). When receiver operating characteristic (ROC) curves were used
      to determine optimal cutoffs for ADC and DW image values, the region of infarct
      growth was significantly correlated with only the mismatch between initial
      qualitative DW image and quantitative DW image signal intensity ratio (cutoff
      value, 1.19; R = 0.652; P = .022). CONCLUSION: Pixel-based thresholds applied to
      ADC or DW image signal intensity maps were not accurate prognostic measures of
      tissue at risk. Quantitative DW images or ADC maps may provide added information
      not obtained by visual inspection of the qualitative DW image map.

PMID- 15466326
TI  - High-resolution diffusion tensor imaging of the brain stem at 3 T.
AB  - Diffusion tensor imaging with 1.8-mm isotropic resolution was performed to
      delineate structures of the brain stem. High-resolution single-shot imaging was
      achieved by the combination of a high-field magnet (3T) and the SENSitivity
      Encoding (or SENSE) parallel imaging technique. Various structures in the brain
      stem, such as the inferior olivary nuclei, deep cerebellar nuclei, some cranial
      nerves, and white matter tracts were identified, which have been difficult to
      appreciate by conventional MR techniques.

PMID- 15466328
TI  - Topographical distribution of pontocerebellar microbleeds.
AB  - BACKGROUND AND PURPOSE: Microbleeds (MBs) visualized by use of T2*-weighted
      gradient-echo MR imaging are pathologic blood-breakdown products after tiny
      cerebral hemorrhages. The topographic distribution of the lesions has not been
      compared with that of symptomatic intracerebral hemorrhage (ICH). The purpose of
      this study was to evaluate the distribution of MBs in the pontocerebellar region
      and to compare it with the distribution of ICHs reported in the literature.
      METHODS: We examined 164 consecutive hypertensive patients with ischemic
      infarction or spontaneous ICH over a 1-year period. Two experienced
      neuroradiologists assessed cerebral localization of MBs without prior knowledge
      of the clinical information and in consensus. After obtaining 16 standard axial
      brain images, we analyzed the anatomic locations and the vascular territories of
      the MBs in the pontocerebellar area. RESULTS: We detected 374 pontocerebellar MBs
      in 40 patients (8.1 +/- 12.7). Pontine MBs showed a significant predilection for
      the central portion (middle part along the axial plane, 3.4 +/- 4.9 [P < .01];
      medial part along the coronal plane, 3.4 +/- 4.1 [P < .01]) and mostly belonged
      to the territory of the anteromedial group arising from the basilar artery.
      Cerebellar MBs had a frequent distribution around the dentate nucleus, occurring
      significantly more in the lower half, in the medial part (3.4 +/- 4.6; P < .01),
      and in the middle part along the axial plane (4.8 +/- 7.0; P < .01). CONCLUSION:
      These findings were similar to the topography of ICH described in the literature.
      Our results suggest that MBs may be a lesional marker for ICH.

PMID- 15466329
TI  - Reperfusion cellular injury in an animal model of transient ischemia.
AB  - BACKGROUND AND PURPOSE: Early thrombolytic therapy is encouraged in hyperacute
      stroke, although this might result in delayed reperfusion injury. Our purpose was
      to investigate the serial changes in cerebral perfusion following transient
      ischemia by means of MR imaging and to correlate them with the histologic
      findings obtained by using the TdT-mediated dUTP-biotin nick-end labeling (TUNEL)
      assay. METHODS: One-hour transient occlusion of the middle cerebral artery was
      produced in 10 cats. Serial perfusion-weighted MR imaging was performed for 3
      days after reperfusion. The reperfusion characteristics in each region of the
      brain were classified into four groups according to the serial perfusion MR
      imaging status: normal perfusion (N), continuous hyperperfusion (I), early
      hyperperfusion and gradual decrease (II), and persistent hypoperfusion (III).
      After the last imaging session, a specimen was obtained, and TUNEL staining was
      performed. TUNEL-positive cells were counted under a high-power-field (HPF) light
      microscope (x200). The degree of TUNEL positivity was compared among the four
      reperfusion groups classified on the basis of serial perfusion-weighted imaging
      findings. RESULTS: Group N had 16.8 +/- 5.1 TUNEL-positive cells per HPF. Groups
      I and II had a statistically significant increase in TUNEL positivity (39.5 +/-
      13.4 and 43.6 +/- 16.7 cells per HPF; P < .01, one-way analysis of variance),
      whereas group III had a statistically insignificant increase in TUNEL positivity
      (23.3 +/- 6.9 cells per HPF). CONCLUSION: Reperfusion followed by hyperperfusion
      induced cellular damage, although the initial MR imaging findings were normal.
      The inclusion of anti-reperfusion injury therapy should be considered in
      thrombolytic treatment.

PMID- 15466330
TI  - Basilar artery herniation into the sphenoid sinus resulting in pontine and
      cerebellar infarction: demonstration by three-dimensional time-of-flight MR
      angiography.
AB  - We report a unique case of basilar artery herniation into the sphenoid sinus
      caused by a traumatic skull base fracture, with persistent patency of the basilar
      artery. Clinical and imaging features, as well as the relevant literature, are
      described.

PMID- 15466331
TI  - Thrombosis of the internal cerebral vein associated with transient unilateral
      thalamic edema: a case report and review of the literature.
AB  - Thrombosis of the deep venous system presenting with bilateral thalamic
      infarction or edema is a common finding, but unilateral venous thrombosis
      presenting with unilateral thalamic edema is extremely rare. We report a case of
      a patient with this unusual condition presenting with nonspecific clinical signs
      and symptoms. CT and MR imaging revealed a unilateral thalamostriate lesion. The
      imaging sign that was most helpful in establishing the diagnosis, however, was
      the MR finding of a thrombus in a single internal cerebral vein.

PMID- 15466332
TI  - Computational replicas: anatomic reconstructions of cerebral vessels as volume
      numerical grids at three-dimensional angiography.
AB  - BACKGROUND AND PURPOSE: We present a relatively simple approach that physicians
      can use to reconstruct cerebral vessels as 3D numerical grids or computational
      replicas. The method accurately duplicates their geometry to provide computer
      simulations of their blood flow. METHODS: Initial images were obtained by using
      any medical imaging technique, such as MR angiography, CT angiography, or 3D
      digital subtraction angiography. The data were collected in DICOM format and
      converted by a DICOM reader into a 3D gray-scale raster image. The image was then
      processed by using commercial visualization and mesh generation software, which
      allowed extraction of the luminal surface of the blood vessel (by using the
      isosurfacing technique). The subsequent final output was an unstructured
      tetrahedral grid that can be directly used for detailed analysis of cerebral
      vascular geometry for patient-specific simulations of blood flow. RESULTS: Four
      examples of grid reconstruction and blood flow simulation for patients with
      ruptured aneurysms were validated with angiographic and operative findings. The
      ruptured areas were correlated with areas of high fluid-induced wall-shear
      stress. CONCLUSION: This approach promises to be a practical tool for planning
      treatment and follow-up of patients after neurosurgical or endovascular
      interventions with 3D angiography. The proposed commercial packages or
      conceptually similar ones seem to be relatively simple and suitable for direct
      use by neurosurgeons or neuroradiologists.

PMID- 15466333
TI  - Multiple cerebral aneurysms and subarachnoid hemorrhage in a patient with
      Alagille syndrome.
AB  - Although intracranial hemorrhage has frequently been found responsible for
      mortality in adult patients with Alagille syndrome (AGS), no specific underlying
      cause has been identified. We describe the case of severe subarachnoid hemorrhage
      in a 30-year-old woman harboring five intracranial aneurysms and multiple
      peripheral vascular anomalies. To evaluate a possible higher incidence of
      intracranial aneurysms, a study of the cerebral vasculature in all AGS patients
      by using noninvasive imaging techniques should be considered.

PMID- 15466334
TI  - Selective endovascular treatment of intracranial aneurysms with sapphire coils.
AB  - BACKGROUND AND PURPOSE: Endovascular treatment with detachable coils is an
      accepted alternative to surgical clip placement for intracranial aneurysms. The
      purpose of this study was to evaluate the safety and reliability of the Sapphire
      coil, a new platinum coil for the treatment of intracranial aneurysms. METHODS:
      Between August and September 2003, 20 consecutive patients (13 women, seven men;
      mean age, 49 years; range, 33-77 years) with 20 intracranial aneurysms were
      referred to our department for endovascular treatment. Fifteen patients presented
      with subarachnoid hemorrhage, whereas five had asymptomatic, unruptured
      aneurysms. All patients were treated by selective endosaccular coil placement
      with the new coils. The remodeling technique was used in five wide-neck
      aneurysms. Clinical outcomes were assessed with the modified Glasgow Outcome
      Scale. RESULTS: Aneurysmal occlusion with the new coils alone was successful in
      16 patients and resulted in 12 complete occlusions and four neck remnants.
      Because of the limited Sapphire product line, additional Guglielmi detachable
      coils (GDCs) were required in four patients, two of whom received one 3D GDC of 3
      mm diameter and two of whom received Ultra-Soft GDCs. Technical complication
      (stretching of a coil) occurred in one patient. Clinical outcomes were excellent
      in 14 patients and good in two. CONCLUSION: Although the study was limited by its
      small patient population, the results show that selective endovascular treatment
      of intracranial aneurysms with Sapphire coils was not associated with an
      unexpected incidence of adverse events. Excellent anatomic and clinical results
      that were obtained in most patients suggest that Sapphire coils may have value in
      the treatment of intracranial aneurysms.

PMID- 15466335
TI  - Additional coiling of previously coiled cerebral aneurysms: clinical and
      angiographic results.
AB  - BACKGROUND AND PURPOSE: Some cerebral aneurysms that have been coiled reopen over
      time and additional treatment should be considered to reduce the risk of
      recurrent hemorrhage. Our purpose was to assess procedural complications and
      angiographic results of additional coiling in patients with previously coiled but
      reopened aneurysms and to evaluate protection against (re)bleeding. METHODS: We
      compared procedural complications of initial coiling of 488 aneurysms in 439
      patients with those of 53 additional coiling procedures in 41 reopened aneurysms
      in 40 patients. Angiographic results of additional coiling were assessed. We
      compared episodes of (re)bleeding in patients with complete or near-complete
      aneurysm occlusion after additional coiling with those of patients with
      incomplete aneurysm occlusion at 6-month follow-up angiography who were not
      additionally treated or who still had incomplete occlusion after additional
      coiling. RESULTS: Thirty-five procedural complications occurred in 488 initial
      coiling procedures, and no complications occurred in 53 additional procedures.
      Complete or near-complete angiographic occlusion after additional coiling was
      obtained in 31 (76%) of 41 aneurysms. Rebleeding occurred in two of 29 patients
      with incomplete aneurysm occlusion but in none of the 31 patients with complete
      or near-complete occlusion after additional coiling. CONCLUSION: Additional
      coiling of previously coiled aneurysms has a low procedural complication rate and
      leads to sufficient occlusion in most aneurysms. The data indicate that
      successful additional coiling decreases the risk of rebleeding.

PMID- 15466336
TI  - Radioactive coil embolization of intracranial aneurysms: minimal inventory to
      reach target activities in a virtual series of 154 patients.
AB  - BACKGROUND AND PURPOSE: Recanalization after selective endovascular treatment of
      intracranial aneurysms with platinum coils has been widely reported in the
      literature. Beta radiation emitted from (32)P ion-implanted coils can prevent
      recanalization in animal models. A complete inventory of radioactive coils may
      not be realistic; our hypothesis was that it might not be necessary to reach
      target activities in most aneurysms. A limited supply of three or four types of
      coils may decrease the inventory difficulties related to the use of an isotope
      with a half-life of 2 weeks. METHODS: We reviewed 154 aneurysms selectively
      treated with standard coils. We calculated the volumetric activity obtained if
      all coils (simulation 1) were radioactive with linear activities of 0.13
      (scenario I) or 0.26 microCi/cm (scenario II). Then, we simulated a treatment
      with standard coils plus a selection of radioactive coils limited to three
      (simulation 2) or four types of commonly used coils (simulation 3). Resulting
      activities were calculated and reported to the lesion volume. For each scenario
      and simulation, the percentage of lesions, in which the target volumetric
      activity (0.018 microCi/mm3) was reached, was reported. RESULTS: Success in
      reaching target volumetric activities varied from 55-99% according to different
      simulations. A supply of four types of coils was sufficient to reach target
      activities in 86-95% of patients commonly treated in our institution. Target
      activities were difficult to reach in giant aneurysms. CONCLUSION: It is feasible
      to reach target activities in most lesions by using a limited coil supply.

PMID- 15466337
TI  - HyperForm remodeling-balloon for endovascular treatment of wide-neck intracranial
      aneurysms.
AB  - A new, very compliant remodeling balloon microcatheter has been developed for the
      treatment of difficult wide-neck intracranial aneurysms (eg, arterial bifurcation
      or small artery aneurysms). We report selective embolization by the use of the
      remodeling technique with the HyperForm balloon in 16 consecutive patients with a
      wide-neck intracranial aneurysm located on an arterial bifurcation or a small
      artery or both.

PMID- 15466338
TI  - Temporary balloon occlusion to test adequacy of collateral flow to the retina and
      tolerance for endovascular aneurysmal coiling.
AB  - Two carotid ophthalmic artery aneurysms with incorporation of the artery into the
      neck were referred for endovascular assessment. Temporary balloon occlusion at
      the aneurysm neck was performed in an attempt to assess the adequacy of
      collateral flow to the retina. During inflation, the patients reported visual
      deterioration that resolved upon deflation, which indicates that collateral blood
      flow was insufficient. The patients were referred for surgical clipping to ensure
      preservation of the ophthalmic artery.

PMID- 15466339
TI  - Lingual artery bifurcation aneurysms for training and evaluation of neurovascular
      devices.
AB  - We present a canine lingual artery bifurcation aneurysm and assess its value for
      training in endovascular techniques and testing new embolic agents. The
      experimental aneurysm described herein mirrors human bifurcation aneurysms, and
      with this model, we sought to reproduce endovascular technical difficulties.
      However, the lesions created in this canine model did not show angiographic or
      histologic evidence of aneurysmal recurrence. We conclude that this model may be
      useful for training in endovascular techniques, but because of the lack of
      sufficient aneurysmal recurrence, it is not suitable for evaluating new embolic
      agents.

PMID- 15466340
TI  - Recanalization by mechanical embolus disruption during intra-arterial
      thrombolysis in the carotid territory.
AB  - BACKGROUND AND PURPOSE: Mechanical disruption of a clot with a microcatheter and
      a guidewire has not been detailed in conjunction with intra-arterial thrombolysis
      in patients with acute ischemic stroke. The purpose of this study was to evaluate
      the efficacy of mechanical disruption of an embolus in the carotid artery
      distribution. METHODS: We analyzed clinical and radiologic findings and
      functional outcomes 3 months after thrombolysis with mechanical disruption.
      Outcomes were classified as good for modified Rankin scale (mRS) scores of 0-2,
      moderate for mRS scores of 3, and poor for death and mRS scores of 4 or 5.
      RESULTS: Twenty-three consecutive patients with severe hemispheric symptoms were
      treated with several methods of mechanical embolus disruption during the intra
      arterial administration of urokinase. Twelve patients had occlusions of the
      proximal middle cerebral artery (MCA), and 11 had occlusions of the distal
      internal carotid artery (ICA). Recanalization was observed in all patients with
      MCA occlusions and in 10 (91%) with ICA occlusions. Outcomes were good in nine
      patients (75%) with MCA occlusions and in four (36.4%) with ICA occlusions. Early
      management of vessel perforation, caused by a microguidewire tip in two patients,
      resulted in early hemostasis. Neither patient had a major deficit attributable to
      the complication. CONCLUSION: A high incidence of recanalization and clinical
      improvement can be observed in patients with occlusions of not only the proximal
      MCA but also the distal ICA. This method might be an effective additional option
      to intra-arterial thrombolysis for acute distal ICA and proximal MCA occlusions.

PMID- 15466341
TI  - Factors predictive of cerebral hyperperfusion after carotid angioplasty and stent
      placement.
AB  - BACKGROUND AND PURPOSE: Cerebral hyperperfusion syndrome has been increasingly
      reported as a complication of carotid angioplasty and stent placement. The aim of
      the present study was to determine significant predictors of hyperperfusion
      phenomenon after carotid angioplasty and stent placement. METHODS: We
      retrospectively reviewed 30 consecutive patients with unilateral severe carotid
      stenosis who underwent angioplasty and stent placement. Resting cerebral blood
      flow (CBF) and cerebral vasoreactivity (CVR) to acetazolamide challenge were
      quantitatively measured to evaluate cerebral hemodynamic reserve. Split-dose
      [(123)I] iodoamphetamine single photon emission CT (SPECT) was performed before
      and 7 days after carotid angioplasty and stent placement. Technetium-99m
      hexamethylpropyleneamine oxime (HMPAO) SPECT was performed immediately after the
      procedure. RESULTS: Three patients had cerebral hyperperfusion phenomenon
      immediately after angioplasty and stent placement, as shown by HMPAO SPECT: One
      developed status epilepticus 2 weeks after the procedure. Significant predictors
      of hyperperfusion included patient age, pretreatment CVR, and pretreatment
      asymmetry index ([ipsilateral resting CBF/contralateral resting CBF] x 100).
      Variables determined not to be significant risk factors included pretreatment
      resting CBF value, degree of carotid stenosis, and interval from the onset of
      ischemic symptoms. CONCLUSION: Significant predictors of hyperperfusion
      phenomenon after carotid angioplasty and stent placement included patient age,
      pretreatment CVR, and pretreatment asymmetry index. Pretreatment CBF
      measurements, including those obtained by quantifying CVR and performing SPECT
      immediately after the procedure may aid in identifying patients at risk and in
      initiating careful monitoring and control of blood pressure to prevent
      hyperperfusion syndrome.

PMID- 15466342
TI  - The use of hydrocoil for parent artery occlusion.
AB  - The HydroCoil Embolic System (HES) comprises a platinum microcoil coated with an
      expansile polymer and is approved by the United States Food and Drug
      Administration for cerebral aneurysm occlusion. We report a series of five cases,
      two in the internal carotid artery and three in the vertebral artery, in which
      the HES was used for parent artery occlusion procedures. In each of these cases,
      the HES allowed rapid, short-segment occlusion.

PMID- 15466343
TI  - Successful revascularization of acute carotid stent thrombosis by facilitated
      thrombolysis.
AB  - A 64-year-old woman undergoing protected carotid artery stent placement developed
      acute stent thrombosis despite pretreatment with combined antiplatelet therapy. A
      reduced dose of recombinant tissue plasminogen activator and a half-dose bolus of
      abciximab were administered intra-arterially via superselective catherization
      followed by systemic intravenous infusion of abciximab for 12 hours. Control
      angiography showed complete restoration of blood flow paralleled by neurologic
      improvement.

PMID- 15466344
TI  - N-butylcyanoacrylate embolization of a middle meningeal artery aneurysm in a
      patient with neurofibromatosis type 2.
AB  - Aneurysms of the middle meningeal artery are rare, with no documented association
      with neurofibromatosis type 2 (NF2). Middle meningeal artery aneurysm
      embolization with N-butylcyanoacrylate has not been described, and altogether,
      few accounts exist regarding the endovascular management of these unusual
      aneurysms. In this case report of a patient with NF2, an unruptured middle
      meningeal artery aneurysm was prophylactically embolized in a previously
      unreported fashion by using N-butylcyanoacrylate acrylic glue.

PMID- 15466345
TI  - Experimental flat-panel high-spatial-resolution volume CT of the temporal bone.
AB  - BACKGROUND AND PURPOSE: A CT scanner employing a digital flat-panel detector is
      capable of very high spatial resolution as compared with a multi-section CT
      (MSCT) scanner. Our purpose was to determine how well a prototypical volume CT
      (VCT) scanner with a flat-panel detector system defines fine structures in
      temporal bone. METHODS: Four partially manipulated temporal-bone specimens were
      imaged by use of a prototypical cone-beam VCT scanner with a flat-panel detector
      system at an isometric resolution of 150 microm at the isocenter. These specimens
      were also depicted by state-of-the-art multisection CT (MSCT). Forty-two
      structures imaged by both scanners were qualitatively assessed and rated, and
      scores assigned to VCT findings were compared with those of MSCT. RESULTS:
      Qualitative assessment of anatomic structures, lesions, cochlear implants, and
      middle-ear hearing aids indicated that image quality was significantly better
      with VCT (P < .001). Structures near the spatial-resolution limit of MSCT (e.g.,
      bony covering of the tympanic segment of the facial canal, the incudo-stapedial
      joint, the proximal vestibular aqueduct, the interscalar septum, and the
      modiolus) had higher contrast and less partial-volume effect with VCT.
      CONCLUSION: The flat-panel prototype provides better definition of fine osseous
      structures of temporal bone than that of currently available MSCT scanners. This
      study provides impetus for further research in increasing spatial resolution
      beyond that offered by the current state-of-the-art scanners.

PMID- 15466346
TI  - Clinical applications of tumor volume measurements for predicting outcome in
      patients with squamous cell carcinoma of the upper aerodigestive tract.
AB  - Gross tumor volume (GTV) at the primary site, as derived from pretreatment CT
      findings, can help predict local control of squamous cell carcinoma at different
      head and neck subsites after treatment with nonsurgical organ preservation. Local
      recurrence is more likely with large tumors than with small lesions in the same
      anatomic subsite, and GTV is often more strongly associated with local control
      than is tumor stage. This review discusses tumor volume calculation-technique,
      current literature, and potential clinical applications-and aims to help the
      reader to understand the role of GTV calculations and to integrate this knowledge
      into clinical practice.

PMID- 15466347
TI  - A review of two cases of fenestrated internal jugular veins as seen by CT
      angiography.
AB  - Venous fenestrations are a rarely seen entity in the neck. Although their
      clinical significance is questionable, their importance in presurgical planning
      may be considerable. We present a report of two cases of internal jugular vein
      fenestration.

PMID- 15466348
TI  - Percutaneous translumbar spinal cord compression injury in dogs from an
      angioplasty balloon: MR and histopathologic changes with balloon sizes and
      compression times.
AB  - BACKGROUND AND PURPOSE: Our previous model of spinal cord injury (SCI) included
      six dogs undergoing 30-minute compression with a balloon in the subarachnoid
      space. We determined whether various balloon sizes and compression times creates
      a gradation of injuries. METHODS: In 17 dogs (including our original six),
      angioplasty balloons 2, 4, or 7 mm in diameter (2 cm long) were inflated at T6
      for 30, 120, or 240 minutes. T1- and T2-weighted, gadolinium-enhanced, and short
      tau inversion recovery (STIR) MR images were obtained at 1.5 T. Spinal canal
      occlusion (SCO) was measured as balloon area-spinal cord area. Hematoxylin-eosin
      and beta amyloid precursor protein staining were performed to demonstrate
      hemorrhage and axonal injury, respectively. Injuries were scored as mild,
      moderate, or severe. Trends were assessed with one-way analysis of variance.
      RESULTS: SCO was 12.5-20% for 2-mm balloons, 28-56% for 4 mm, and 62-82% for 7
      mm. No abnormalities were seen with SCO <30%. T1- and T2-weighted images had the
      poorest diagnostic performance; STIR images were best for predicting hemorrhage
      and axonal injury. Hemorrhage was demonstrated more frequently than was axonal
      injury. SCO (P < .0001) and hemorrhage (P = .002) significantly increased with
      balloon size. Longer inflation times tended to increase injuries for a given
      size, but differences were not significant. CONCLUSION: Compression injuries
      depended on the level of SCO. The compression times tested had less effect than
      the degree of compression. The value of 1.5-T MR imaging varied with the sequence
      and improved with contrast enhancement. STIR images showed SCIs not otherwise
      detected.

PMID- 15466349
TI  - Multiple hibernomas in a 1-month-old female infant.
AB  - Hibernoma is a rare benign soft tissue tumor composed of remnants of fetal brown
      fat. It has only rarely been reported in the literature in patients ranging in
      age from 2 to 75 years. We present a case of multiple hibernomas occurring in a 1
      month-old infant.

PMID- 15466350
TI  - Serial antenatal sonographic observation of cerebral dural sinus malformation.
AB  - Dural sinus malformation is an extremely rare congenital cerebrovascular
      malformation. We report serial antenatal sonographic findings in two patients
      with dural sinus malformation. Sonography can reveal dural sinus malformation at
      24 weeks' gestation. Correct and early diagnosis may help determine the
      appropriate place, timing, and mode of delivery, which may result in a better
      therapeutic course and patient outcome.

PMID- 15466352
TI  - Upper extremity reconstruction following resection of soft tissue sarcomas: a
      functional outcomes analysis.
AB  - BACKGROUND: Treatment for soft tissue sarcoma of the upper extremity has evolved
      to include limb salvage techniques. We reviewed our experience with limb salvage
      therapy for upper extremity sarcomas with an emphasis on functional outcomes
      following the reconstructive surgery. METHODS: A retrospective analysis was
      performed of 81 consecutive patients with soft tissue sarcoma of the upper
      extremity who had limb salvage therapy with reconstruction by a plastic surgeon.
      Univariate and multivariate regression analyses of relevant outcome variables
      were performed. Enneking functional scores were obtained from 43 patients.
      RESULTS: The study included 16 microvascular reconstructions and 67 non
      microvascular reconstructions for a total of 83 reconstructions in 81 patients.
      The mean defect size was 129 cm(2) (standard deviation: 106 cm(2)). The mean
      total functional score was 23.1 (range, 9 to 30). Any reconstruction-related
      complication and preoperative chemotherapy use were associated with a 7.3 point
      (P = .03) and 4.7 point (P = .01) decrease in total functional score,
      respectively. Kaplan-Meier product-limit analysis showed 82% 5-year overall
      survival and 67% 5-year disease-free survival rates. CONCLUSIONS: For soft tissue
      sarcoma of the upper extremity, limb salvage with good functional outcome is
      possible with a judicious approach to reconstruction.

PMID- 15466353
TI  - Expression of cancer-testis antigen (CTA) genes in intrahepatic
      cholangiocarcinoma.
AB  - BACKGROUND: Cancer-testis antigens (CTA), such as MAGE, are selectively expressed
      in various types of human neoplasms but not in normal tissues other than testis.
      This characteristic feature of CTA makes them promising antigens for cancer
      specific immunotherapy. METHODS: We investigated the expression of five genes,
      including MAGE-1, MAGE-3, NY-ESO-1, SCP-1, and SSX-4, in 20 surgical samples of
      intrahepatic cholangiocarcinomas (IHCC) using reverse transcription-polymerase
      chain reaction. To visualize the localization of MAGE proteins, we performed
      immunohistochemical studies. Furthermore, the correlation between the CTA
      expression and DNA methylation status was studied in three bile duct cancer cell
      lines. RESULTS: Expression of MAGE-1, MAGE-3, NY-ESO-1, SCP-1, and SSX-4 was
      recognized in 4, 4, 2, 6, and 3 of all 20 cases, respectively. In contrast, the
      expressions of five genes were not recognized at all in the corresponding normal
      tissues. In 10 cases (50%), the tumors expressed at least one of the five CTA. An
      immunohistochemical analysis of MAGE proteins demonstrated homogenous or focal
      distributions in cytoplasm of the IHCC. Using a demethylating agent, MAGE-1, NY
      ESO-1, SCP-1, and SSX-4 were induced in two of three cell lines, whereas MAGE-3
      was not. CONCLUSIONS: Half of the tumor tissues of IHCC expressed at least one of
      the CTA. Some of the patients with IHCC, therefore, should be candidates for
      potentially useful cancer-specific immunotherapy.

PMID- 15466354
TI  - The computer synoptic operative report--a leap forward in the science of surgery.
AB  - BACKGROUND: Quality of surgery is a proven prognostic factor in many tumors. It
      is critical to ensure that an effective method is in place to evaluate surgery
      accurately. MATERIAL AND METHODS: A provincial Cancer Surgery Working Group
      designed and piloted a computerized synoptic operative report template (WebSMR)
      in rectal cancer surgery, to replace the standard narrative operative record
      (NR). This included a precise description of the procedure, data on demographics,
      diagnostic evaluation, staging, and functional measures. A total of 70 items for
      anterior resection (AR) and 63 items for abdominoperinal excision (APR) were
      included. The WebSMR was assessed for comparison with 40 NR randomly selected
      from seven hospitals in Southern Alberta from 2001 to 2003. RESULTS: The NR
      contained 45.9% of the specified data elements and the WebSMR captured 99%. The
      most complete NR data (68.8% to 97%) concerned hospital and patient data,
      anesthetist and surgeon information, approach, and closure details. The important
      details of laparotomy and tumor resection were the next most complete data (33.5%
      to 47.5%) and the least complete (0 to 25%) concerned preoperative treatment,
      comorbidity, and metastatic and local assessment. All differences among these
      groups were statistically different (P < .001). No statistically significant
      differences were seen in the completeness of the NR according to the type of
      surgery (AR vs. APR; P = .1) or the dictating surgeon (colorectal vs. general vs.
      resident; P = .175). The time needed to complete the WebSMR test was only 6
      minutes. CONCLUSION: The science of surgical technique can be better measured by
      this unique instrument and will create accountability in surgery.

PMID- 15466355
TI  - Veterans Administration support for medical research: opinions of the endangered
      species of physician-scientists.
AB  - Over the past three decades the Veterans Affairs (VA) Research program has
      evolved into a powerful, peer-reviewed funding mechanism for basic and
      translational research that has resulted in numerous important contributions to
      medical science and improvements in patient care. Continuity in VA Merit Review
      funding has fostered and nurtured the scientific careers of a large number of
      physician-scientists who have remained devoted to the mission of performing
      creative and innovative research that affects the patient care mission of the VA.
      VA medical research policies have undergone a major overhaul in the past year.
      Although many of these changes (de-emphasizing bench research and revamping the
      peer review process) have recently been reversed, the future direction of VA
      research remains in flux. The goal of this manuscript is to demonstrate the
      importance of the Merit Review medical research funding mechanism not just to the
      VA, but to the entire nation's health care system. To achieve this goal, the
      opinions of 65 established VA medical investigators were obtained regarding the
      past success and future direction of VA research. The conclusions reached include
      the following. 1) Merit Review research funding has been essential to the
      training, recruitment, and retention of productive VA physician-scientists. 2)
      The VA research program has contributed both basic and clinical innovations that
      have led to improvements in medical care. Contributions of VA researchers to
      excellence in many aspects of patient care at VA hospitals have been
      extraordinary. 3) Development of initiatives that entice outstanding Ph.D.'s to
      develop their careers in the VA has been crucial to the success of the program.
      4) The VA research program has fostered a mutually beneficial relationship with
      affiliated medical schools. 5) Better methods to quantify VA research
      contributions and outcomes are essential for future program development.

PMID- 15466356
TI  - Mitochondrial poly(ADP-ribosylation): from old data to new perspectives.
AB  - Poly(ADP-ribosylation) is involved in DNA repair and replication, transcription,
      and cell death. For a long time, only one poly(ADP-ribosylating) enzyme was
      known, named ADPRT/PARP (EC 2.4.2.30). The recent discovery of a family of PARPs
      has provided a high degree of complexity in the field. Moreover, the finding that
      poly(ADP-ribosylation) is not confined to the nucleus but is also carried out by
      cytoplasmic enzymes supports the idea that it could regulate proteins localized
      in different cellular compartments. In this respect, a reappraisal of the
      literature on mitochondrial poly(ADP-ribosylation) could be useful, as well as a
      discussion of its relevance regarding the current "hot" view of poly(ADP
      ribosylation) as a mediator of cell death.

PMID- 15466357
TI  - Cloning and gene silencing of LAT2, the L-3,4-dihydroxyphenylalanine (L-DOPA)
      transporter, in pig renal LLC-PK1 epithelial cells.
AB  - Organ-specific overexpression of type 2 L-amino acid transporter (LAT2) in the
      kidney of the spontaneous hypertensive rat (SHR), accompanied by an enhanced
      ability to take up L-DOPA, may constitute the basis for the enhanced renal
      production of dopamine in the SHR in an attempt overcome the deficient dopamine
      mediated natriuresis. To understand the physiological role of LAT2-mediated L
      DOPA handling, we used 21-nucleotide small interfering RNA duplexes (siRNA) to
      specifically suppress LAT2 expression in LLC-PK1 cells, a cell line that retains
      several properties of proximal tubular epithelial cells and takes up L-DOPA
      largely through Na+-independent transporters. After cloning the LLC-PK1 LAT2
      gene, one target region of LAT2 mRNA (nt 97-117) was selected by scanning the
      length of the LAT2 gene for AA-dinucleotide sequences and downstream 19
      nucleotides. Levels of LAT2 cDNA, determined by real-time quantitative RT-PCR,
      were markedly (P<0.05) reduced by LAT2 siRNA but not by the mismatch LAT2 siRNA.
      The LAT2 siRNA but not the mismatch LAT2 siRNA, reduced by 85% [14C]-L-DOPA
      accumulation, a time- and concentration-dependent effect. The efflux of
      intracellular [14C]-L-DOPA was markedly increased (P<0.05) by L-DOPA and L
      leucine. The [14C]-L-DOPA outward transport was decreased 90% by LAT2 siRNA, but
      not by the mismatch LAT2 siRNA. However, treatment with the siRNA LAT2 did not
      affect the L-DOPA-induced fractional outflow of [14C]-L-DOPA. The Na+-independent
      and pH-sensitive L-DOPA transporter may include the hetero amino acid exchanger
      LAT2, whose activation results in trans-stimulation of L-DOPA outward transfer.
      Soares-da-Silva, P., Serrao, M. P., Joao Pinho, M., Bonifacio, M. J. Cloning and
      gene silencing of LAT2, the L-3,4-dihydroxyphenylalanine (L-DOPA) transporter, in
      pig renal LLC-PK1 epithelial cells.

PMID- 15466358
TI  - Acute exercise activates nuclear factor (NF)-kappaB signaling pathway in rat
      skeletal muscle.
AB  - Two studies were performed to investigate the effects of an acute bout of
      physical exercise on the nuclear protein kappaB (NF-kappaB) signaling pathway in
      rat skeletal muscle. In Study 1, a group of rats (n=6) was run on the treadmill
      at 25 m/min, 5% grade, for 1 h or until exhaustion (Ex), and compared with a
      second group (n=6) injected with two doses of pyrrolidine dithiocarbamate (PDTC,
      100 mg/kg, i.p.) 24 and 1 h prior to the acute exercise bout. Three additional
      groups of rats (n=6) were injected with either 8 mg/kg (i.p.) of
      lipopolysaccharide (LPS), 1 mmol/kg (i.p.) t-butylhydroperoxide (tBHP), or saline
      (C) and killed at resting condition. Ex rats showed higher levels of NF-kappaB
      binding and P50 protein content in muscle nuclear extracts compared with C rats.
      Cytosolic IkappaBalpha and IkappaB kinase (IKK) contents were decreased, whereas
      phospho-IkappaBalpha and phospho-IKK contents were increased, comparing Ex vs. C.
      The exercise-induced activation of NF-kappaB signaling cascade was partially
      abolished by PDTC treatment. LPS, but not tBHP, treatment mimicked and
      exaggerated the effects observed in Ex rats. In Study 2, the time course of
      exercise-induced NF-kappaB activation was examined. Highest levels of NF-kappaB
      binding were observed at 2 h postexercise. Decreased cytosolic IkappaBalpha and
      increased phosphor-IkappaBalpha content were found 0-1 h postexercise whereas P65
      reached peak levels at 2-4 h. These data suggest that the NF-kappaB signaling
      pathway can be activated in a redox-sensitive manner during muscular contraction,
      presumably due to increased oxidant production. The cascade of intracellular
      events may be the overture to elevated gene expression of manganese superoxide
      dismutase reported earlier (Pfluegers Arch. 442, 426-434, 2001).

PMID- 15466359
TI  - Vascular endothelial growth factor receptor-3 in hypoxia-induced vascular
      development.
AB  - Reduced tissue oxygen tension (hypoxia) is appreciated as an efficient stimulus
      for neovascularization. The effect of hypoxia on the very first stages of
      vascular development is, however, less well characterized. Here we show that
      hypoxic conditions (1% O2) potently stimulated formation of an extensive vascular
      network during a discrete stage of mouse embryonal stem cell differentiation. The
      morphological changes correlated with an expanding pool of endothelial cells and
      with activation of the vascular endothelial growth factor-d (Vegf-d) and Vegf
      receptor-3 genes. VEGF receptor-3 expression was confined to vascular endothelial
      cells and analysis of the lymphatic marker Prox-1 revealed no expansion of
      lymphatic endothelial cells. Administration of neutralizing antibodies against
      either VEGF receptor-3 or VEGF receptor-2 impaired vascular network formation,
      whereas neutralizing antibodies against VEGF receptor-1 potentiated development
      of immature vascular structures. In addition, sequestering of VEGF receptor-3
      ligands reduced vascularization in a manner similar to neutralization of VEGF
      receptor-3. We conclude that hypoxia-driven vascular development requires the
      activity of VEGF receptor-3.

PMID- 15466360
TI  - The calcium channel blocker amlodipine exerts its anti-proliferative action via
      p21(Waf1/Cip1) gene activation.
AB  - Proliferation of vascular smooth muscle cells (VSMC) contributes to the
      progression of atherosclerotic plaques. Calcium channel blockers have been shown
      to reduce VSMC proliferation, but the underlying molecular mechanism remains
      unclear. p21(Waf1/Cip1) is a potent inhibitor of cell cycle progression. Here, we
      demonstrate that amlodipine (10(-6) to 10(-8) M) activates de novo synthesis of
      p21(Waf1/Cip1) in vitro. We show that amlodipine-dependent activation of
      p21(Waf1/Cip1) involves the action of the glucocorticoid receptor (GR) and C/EBP
      alpha. The underlying pathway apparently involves the action of mitogen-activated
      protein kinase or protein kinase C, but not of extracellular signal-related
      kinase or changes of intracellular calcium. Amlodipine-induced p21(Waf1/Cip1)
      promoter activity and expression were abrogated by C/EBP-alpha antisense
      oligonucleotide or by the GR antagonist RU486. Amlodipine-dependent inhibition of
      cell proliferation was partially reversed by RU486 at 10(-8) M (58%+/-29%),
      antisense oligonucleotides targeting C/EBP-alpha (91%+/-26%), or antisense mRNAs
      targeting p21(Waf1/Cip1) (96%+/-32%, n=6); scrambled antisense oligonucleotides
      or those directed against C/EBP-beta were ineffective. The data suggest that the
      anti-proliferative action of amlodipine is achieved by induction of the p21
      (Waf1/Cip1) gene, which may explain beneficial covert effects of this widely used
      cardiovascular therapeutic drug beyond a more limited role as a vascular
      relaxant.

PMID- 15466362
TI  - Surfactant and RDS in premature infants.

PMID- 15466361
TI  - Cyclic mechanical strain inhibits skeletal myogenesis through activation of focal
      adhesion kinase, Rac-1 GTPase, and NF-kappaB transcription factor.
AB  - Myogenesis is a multistep developmental program that generates and regenerates
      skeletal muscles. Several extracellular factors have been identified that
      participate in the regulation of myogenesis. Although skeletal muscles are always
      subjected to mechanical stress in vivo, the role of mechanical forces in the
      regulation of myogenesis remains unknown. We have investigated the molecular
      mechanisms by which cyclic mechanical strain modulates myogenesis. Application of
      cyclic mechanical strain using the computer-controlled Flexcell Strain Unit
      increased the proliferation of C2C12 cells and inhibited their differentiation
      into myotubes. Cyclic strain increased the activity of cyclin-dependent kinase 2
      (cdk2) and the cellular level of cyclin A, and inhibited the expression of myosin
      heavy chain and formation of myotubes in C2C12 cultures. The activity of nuclear
      factor-kappa B (NF-kappaB) transcription factor and the expression of NF-kappaB
      regulated genes, cyclin D1 and IL-6, were augmented in response to mechanical
      strain. Cyclic strain also increased the activity of Rho GTPases, especially Rac
      1. The inhibition of Rho GTPases activity, by overexpression of Rho GDP
      dissociation inhibitor (Rho-GDI), inhibited the strain-induced activation of NF
      kappaB in C2C12 cells. Overexpression of either NF-kappaB inhibitory protein
      IkappaBalphaDeltaN (a degradation resistant mutant IkappaBalpha) or Rho-GDI
      blocked the strain-induced proliferation of C2C12 cells. Furthermore,
      overexpression of FRNK, a dominant negative mutant of focal adhesion kinase
      (FAK), inhibited the strain-induced proliferation of C2C12 cells. Our study
      demonstrates that cyclic mechanical strain inhibits myogenesis through the
      activation of FAK, Rac-1, and NF-kappaB.

PMID- 15466364
TI  - Mechanisms mediating insulin resistance in transgenic mice overexpressing mouse
      apolipoprotein A-II.
AB  - We previously demonstrated that transgenic mice overexpressing mouse
      apolipoprotein A-II (apoA-II) exhibit several traits associated with the insulin
      resistance (IR) syndrome, including increased atherosclerosis,
      hypertriglyceridemia, obesity, and IR. The skeletal muscle appeared to be the
      insulin-resistant tissue in the apoA-II transgenic mice. We now demonstrate a
      decrease in FA oxidation in skeletal muscle of apoA-II transgenic mice,
      consistent with reports that decreased skeletal muscle FA oxidation is associated
      with increased skeletal muscle triglyceride accumulation, skeletal muscle IR, and
      obesity. The decrease in FA oxidation is not due to decreased carnitine
      palmitoyltransferase 1 activity, because oxidation of palmitate and octanoate
      were similarly decreased. Quantitative RT-PCR analysis of gene expression
      demonstrated that the decrease in FA oxidation may be explained by a decrease in
      medium chain acyl-CoA dehydrogenase. We previously demonstrated that HDLs from
      apoA-II transgenic mice exhibit reduced binding to CD36, a scavenger receptor
      involved in FA metabolism. However, studies of combined apoA-II transgenic and
      CD36 knockout mice suggest that the major effects of apoA-II are independent of
      CD36. Rosiglitazone treatment significantly ameliorated IR in the apoA-II
      transgenic mice, suggesting that the underlying mechanisms of IR in this animal
      model may share common features with certain types of human IR.

PMID- 15466365
TI  - Inducible nitric oxide synthase modulates lipolysis in adipocytes.
AB  - The role of inducible nitric oxide synthase (iNOS) in the modulation of adipocyte
      lipolysis was investigated. Treatment of white and brown adipose cell lines and
      mouse adipose explants with a mixture of tumor necrosis factor-alpha, interferon
      gamma, and lipopolysaccharide (LPS) doubled the lipolytic rate, and this was
      associated with marked induction of iNOS expression and nitric oxide (NO)
      production. iNOS inhibition by 1400W, aminoguanidine, or L-NIL pretreatment
      further increased the cytokine/LPS-mediated lipolysis by 30% (P < 0.05) in
      cultured adipocytes and in adipose explants. However, this potentiating effect of
      iNOS inhibition was abolished in adipose explants isolated from iNOS knockout
      mice. Pharmacological inhibitors of adenylyl cyclase or protein kinase A reduced
      cytokine/LPS-induced lipolysis and also blunted the potentiating effect of iNOS
      inhibition on the lipolytic rate. Furthermore, addition of the antioxidants l
      cystine and l-glutathione to cytokine/LPS-stimulated adipocytes mimicked the
      lipolytic effect of iNOS inhibition. In conclusion, inhibition of iNOS activity
      in adipocytes potentiates cytokine/LPS-induced lipolysis. This effect was fully
      reversed by adenylyl cyclase and protein kinase A inhibitors but was mimicked by
      cellular antioxidants. These data suggest that iNOS-mediated NO production
      counteracts cytokine/LPS-mediated lipolysis in adipocytes and that this feedback
      mechanism involves an oxidative process upstream of cAMP production in the
      signaling pathway.

PMID- 15466366
TI  - Serum cholestenoic acid as a potential marker of pulmonary cholesterol
      homeostasis: increased levels in patients with pulmonary alveolar proteinosis.
AB  - The conversion of cholesterol into the more polar metabolites 27
      hydroxycholesterol (27-OH) and cholestenoic acid by the cytochrome P450 sterol 27
      hydroxylase is a cholesterol-removal mechanism used by almost all cells. Most of
      the cholestenoic acid present in the circulation originates from the lung, and it
      has been suggested that sterol 27-hydroxylase is of particular importance for
      cholesterol homeostasis in this organ. As an example of pulmonary cholesterol
      accumulation, a known disorder of surfactant homeostasis, pulmonary alveolar
      proteinosis (PAP), was studied. Analysis of bronchoalveolar lavage fluid from PAP
      patients revealed a significant accumulation of the cholesterol metabolites
      cholestenoic acid and 27-OH. This pattern was recapitulated in serum, with a
      significant increase in the levels of both cholestenoic acid (P=0.003) and 27-OH
      (P=0.017) in PAP patients compared with healthy controls. Analysis of PAP
      alveolar macrophages did not reveal a significant change in mRNA expression
      levels of either sterol 27-hydroxylase or the cholesterol-esterifying enzyme acyl
      CoA:cholesterol acyltransferase-1. These results are consistent with the
      contention that substrate availability, rather than enzyme expression, is the key
      factor in regulating the production of cholestenoic acid by the lung and that
      serum cholestenoic acid may be a marker of pulmonary cholesterol homeostasis.

PMID- 15466367
TI  - Chylomicron remnant uptake in the livers of mice expressing human apolipoproteins
      E3, E2 (Arg158-->Cys), and E3-Leiden.
AB  - Apolipoprotein E2 (apoE2) and apoE3-Leiden cause chylomicron remnant accumulation
      (type III hyperlipidemia). However, the degree of dyslipidemia and its penetrance
      are different in humans and mice. Remnant uptake by isolated liver from apoE-/-
      mice transgenic for human apoE2, apoE3-Leiden, or apoE3 was measured. In the
      presence of both LDL receptor (LDLR) and LDL receptor-related protein (LRP),
      remnant uptake was apoE3>E3-Leiden>E2 mice. Absence of LDLR reduced uptake in
      apoE3 and apoE3-Leiden-secreting livers but not in apoE2-secreting livers. LRP
      inhibition with receptor-associated protein reduced uptake in apoE3- and apoE2
      secreting livers, but not in apoE3-Leiden-secreting livers, regardless of the
      presence of LDLR. Fluorescently labeled remnants clustered with LRP in apoE3
      secreting livers only in the absence of LDLR, but clustered in livers that
      expressed apoE2 even in the presence of LDLR, and did not cluster with LRP in
      livers of apoE3-Leiden even in the absence of LDLR. Remnants were reconstituted
      with the three human apoE isoforms. Removal by liver of mApoe-/-/mldlr-/- mice
      expressing the human LDLR was slightly greater than removal in the previous
      experiments with apoE3>E2> E3-Leiden. Thus, in vivo, human apoE2 is cleared
      primarily by LRP, apoE3-Leiden is cleared only by the LDLR, and apoE3 is cleared
      by both.

PMID- 15466368
TI  - Structures and biological activity of phosphorylated dihydroceramides of
      Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis, a recognized periodontal pathogen, synthesizes free
      ceramides as well as other phosphorylated ceramide lipids. The purpose of this
      study was to separate complex lipids of P. gingivalis by high-performance liquid
      chromatography (HPLC) and determine the structures and biological activities of
      the major ceramide classes. Using gas chromatography-mass spectrometry,
      electrospray tandem mass spectrometry (ESI-MS/MS) and NMR analyses, three major
      classes of dihydroceramides were identified in specific HPLC fractions, with all
      classes containing the same dihydroceramide base structures (3-OH isoC(17:0) in
      amide linkage to saturated long-chain bases of 17, 18, or 19 carbons). The free
      dihydroceramide class recovered in HPLC fractions 7-8 revealed little biological
      activity. HPLC fraction 20 dihydroceramides, substituted with 1-O-phosphoglycerol
      and isoC(15:0) linked to the hydroxyl of 3-OH isoC(17:0), significantly
      potentiated interleukin-1beta (IL-1beta)-mediated prostaglandin secretion and
      produced marked alterations in fibroblast morphology. HPLC fraction 28
      dihydroceramides, substituted with 1-O-phosphoethanolamine, demonstrated little
      capacity to potentiate IL-1beta-mediated prostaglandin secretion. The novel
      phosphorylated dihydroceramides synthesized by P. gingivalis demonstrate varying
      biological activities based on the phosphorylated head group substitution and/or
      the addition of esterified fatty acid. These results also demonstrate the strong
      virulence capacity of phosphoglycerol dihydroceramides of P. gingivalis to
      promote inflammatory factor secretion from IL-1beta-treated fibroblasts and to
      produce marked alterations in cell morphology in culture.

PMID- 15466369
TI  - No indications for altered essential fatty acid metabolism in two murine models
      for cystic fibrosis.
AB  - A deficiency of essential fatty acids (EFA) is frequently described in cystic
      fibrosis (CF), but whether this is a primary consequence of altered EFA
      metabolism or a secondary phenomenon is unclear. It was suggested that defective
      long-chain polyunsaturated fatty acid (LCPUFA) synthesis contributes to the CF
      phenotype. To establish whether cystic fibrosis transmembrane conductance
      regulator (CFTR) dysfunction affects LCPUFA synthesis, we quantified EFA
      metabolism in cftr-/-CAM and cftr+/+CAM mice. Effects of intestinal phenotype,
      diet, age, and genetic background on EFA status were evaluated in cftr-/-CAM
      mice, DeltaF508/DeltaF508 mice, and littermate controls. EFA metabolism was
      measured by 13C stable isotope methodology in vivo. EFA status was determined by
      gas chromatography in tissues of cftr-/-CAM mice, DeltaF508/DeltaF508 mice,
      littermate controls, and C57Bl/6 wild types fed chow or liquid diet. After
      enteral administration of [13C]EFA, arachidonic acid (AA) and docosahexaenoic
      acid (DHA) were equally 13C-enriched in cftr-/-CAM and cftr+/+CAM mice,
      indicating similar EFA elongation/desaturation rates. LA, ALA, AA, and DHA
      concentrations were equal in pancreas, lung, and jejunum of chow-fed cftr-/-CAM
      and DeltaF508/DeltaF508 mice and controls. LCPUFA levels were also equal in
      liquid diet-weaned cftr-/-CAM mice and littermate controls, but consistently
      higher than in age- and diet-matched C57Bl/6 wild types. We conclude that cftr-/
      CAM mice adequately absorb and metabolize EFA, indicating that CFTR dysfunction
      does not impair LCPUFA synthesis. A membrane EFA imbalance is not inextricably
      linked to the CF genotype. EFA status in murine CF models is strongly determined
      by genetic background.

PMID- 15466370
TI  - Evidence for altered positional specificity of LCAT in vivo: studies with
      docosahexaenoic acid feeding in humans.
AB  - The percentage of saturated cholesteryl esters (CEs) synthesized by human LCAT is
      several times higher than expected from the sn-2 acyl composition of plasma
      phosphatidylcholine (PC), whereas the synthesis of 20:4 CE and 22:6 CE is much
      lower than expected. To explain these discrepancies, we proposed that LCAT
      transfers some saturated fatty acids from the sn-1 position of PC species that
      contain 20:4 or 22:6 at sn-2. The present studies provide in vivo evidence for
      this hypothesis. We determined the composition and synthesis of CE species in
      plasma of volunteers before and after a 6 week dietary supplementation with
      docosahexaenoic acid (22:6; DHA). In addition to an increase in the DHA content
      of all plasma lipids, there was a significant (+12%; P <0.005) increase of 16:0
      CE, although there was no increase in 16:0 at sn-2 of PC. The increase of DHA in
      CE was much lower than its increase at sn-2 of PC. Ex vivo synthesis of CE
      species in plasma showed a significant (+24%; P <0.005) increase in the synthesis
      of 16:0 CE after DHA supplementation, which correlated positively with the
      increase of 22:6, but not of 16:0, at sn-2 of PC. These results show that the
      positional specificity of human LCAT is altered when the concentration of 16:0
      22:6 PC is increased by DHA supplementation.

PMID- 15466371
TI  - Apolipoprotein E gene polymorphisms and thrombosis and restenosis after coronary
      artery stenting.
AB  - Experimental data support a protective function of apolipoprotein E (apoE)
      against restenosis, the main factor limiting the long-term benefit of
      percutaneous coronary interventions. We investigated the possibility that the
      single nucleotide polymorphisms (SNPs)--219G/T, 113G/C, 334T/C, and 472C/T of the
      gene encoding apoE (APOE) are associated with the incidence of death and
      myocardial infarction or restenosis after stenting in coronary arteries. In
      addition, we asked whether the apoE isotype-related epsilon2/epsilon3/epsilon4
      polymorphism, defined by specific allele combinations (haplotypes) of the 334T/C
      and 472C/T polymorphism, and other APOE haplotypes, derived from all four SNPs
      investigated, are associated with adverse clinical and angiographic outcomes
      after stenting. Our study included 1,850 consecutive patients with symptomatic
      coronary artery disease (CAD) who underwent stent implantation. Follow-up
      angiography was performed in 1,556 patients (84.1%) at 6 months after the
      intervention. We found that none of the APOE SNPs is associated with death and
      myocardial infarction or restenosis after stenting. In addition, we observed no
      relationship between APOE haplotypes and adverse outcomes. In conclusion, the
      APOE -219G/T, 113G/C, 334T/C, and 472C/T polymorphisms, either alone or in
      combination, do not represent genetic markers of the risk of thrombotic and
      restenotic complications in patients with CAD treated with coronary stenting.

PMID- 15466373
TI  - Proteomics in diagnostic pathology: profiling and imaging proteins directly in
      tissue sections.
AB  - Direct tissue profiling and imaging mass spectrometry (MS) provide a molecular
      assessment of numerous expressed proteins within a tissue sample. MALDI MS
      (matrix-assisted laser desorption ionization) analysis of thin tissue sections
      results in the visualization of 500 to 1000 individual protein signals in the
      molecular weight range from 2000 to over 200,000. These signals directly
      correlate with protein distribution within a specific region of the tissue
      sample. The systematic investigation of the section allows the construction of
      ion density maps, or specific molecular images, for virtually every signal
      detected in the analysis. Ultimately, hundreds of images, each at a specific
      molecular weight, may be obtained. To date, profiling and imaging MS has been
      applied to multiple diseased tissues, including human non-small cell lung tumors,
      gliomas, and breast tumors. Interrogation of the resulting complex MS data sets
      using modern biocomputational tools has resulted in identification of both
      disease-state and patient-prognosis specific protein patterns. These studies
      suggest that such proteomic information will become more and more important in
      assessing disease progression, prognosis, and drug efficacy. Molecular histology
      has been known for some time and its value clear in the field of pathology.
      Imaging mass spectrometry brings a new dimension of molecular data, one focusing
      on the disease phenotype. The present article reviews the state of the art of the
      technology and its complementarity with traditional histopathological analyses.

PMID- 15466374
TI  - MMP-12, an old enzyme plays a new role in the pathogenesis of rheumatoid
      arthritis?

PMID- 15466375
TI  - Regulated angiogenesis and vascular regression in mice overexpressing vascular
      endothelial growth factor in airways.
AB  - Angiogenesis and vascular remodeling occurs in many inflammatory diseases,
      including asthma. In this study, we determined the time course and reversibility
      of the angiogenesis and vascular remodeling produced by vascular endothelial
      growth factor (VEGF) in a tet-on inducible transgenic system driven by the CC10
      promoter in airway epithelium. One day after switching on VEGF expression,
      endothelial sprouts arose from venules, grew toward the epithelium, and were
      abundant by 3 to 5 days. Vessel density reached twice baseline by 7 days. Many
      new vessels were significantly larger than normal, were fenestrated, and
      penetrated the epithelium. Despite their mature appearance at 7 days suggested by
      their pericyte coat and basement membrane, the new vessels started to regress
      within 3 days when VEGF was switched off, showing stasis and luminal occlusion,
      influx of inflammatory cells, and retraction and apoptosis of endothelial cells
      and pericytes. Vessel density returned to normal within 28 days after VEGF
      withdrawal. Our study showed the dynamic nature of airway angiogenesis and
      regression. Blood vessels can respond to VEGF by sprouting angiogenesis within a
      few days, but regress more slowly after VEGF withdrawal, and leave a historical
      record of their previous extent in the form of empty basement membrane sleeves.

PMID- 15466376
TI  - Biological significance of focal adhesion kinase in ovarian cancer: role in
      migration and invasion.
AB  - Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is activated by
      integrin clustering. There are limited data regarding the functional role of FAK
      in ovarian cancer migration and invasion. In the current study, FAK expression
      was evaluated in ovarian cell lines (nontransformed and cancer), 12 benign
      ovarian samples, and in 79 invasive epithelial ovarian cancers. All three ovarian
      cancer cell lines overexpressed FAK compared to the nontransformed cells. The
      dominant-negative construct called FAK-related nonkinase (FRNK) was introduced
      into two ovarian cancer cell lines (SKOV3 and 222). FRNK promoted FAK
      dephosphorylation without changing total FAK levels in these cell lines.
      Furthermore, FRNK decreased the in vitro invasive ability of ovarian cancer cells
      by 56 to 85% and decreased migration by 52 to 68%. FRNK-transfected cells also
      displayed poor cell spreading. Immunohistochemical analysis revealed that the
      surface epithelium from all benign ovarian samples had weak FAK expression. In
      contrast, 68% of invasive ovarian cancers overexpressed FAK. FAK overexpression
      was significantly associated with high tumor stage, high tumor grade, positive
      lymph nodes and presence of distant metastasis (all P values <0.05). FAK
      overexpression was also associated with shorter overall survival (P = 0.008).
      Multivariate analysis revealed that FAK overexpression and residual disease >1 cm
      were independent predictors of poor survival. These data indicate that FAK is
      overexpressed in most invasive ovarian cancers and plays a functionally
      significant role in ovarian cancer migration and invasion. Thus, FAK may be an
      important therapeutic target in ovarian carcinoma.

PMID- 15466377
TI  - Transforming growth factor-beta2 induces bronchial epithelial mucin expression in
      asthma.
AB  - The transforming growth factor (TGF)-beta family is important for tissue repair
      in pathological conditions including asthma. However, little is known about the
      impact of either TGF-beta1 or TGF-beta2 on asthmatic airway epithelial mucin
      expression. We evaluated bronchial epithelial TGF-beta1 and TGF-beta2 expression
      and their effects on mucin expression, and the role of TGF-beta1 or TGF-beta2 in
      interleukin (IL)-13-induced mucin expression. Epithelial TGF-beta1, TGF-beta2,
      and mucin expression were evaluated in endobronchial biopsies from asthmatics and
      normal subjects. The effects of TGF-beta1 or TGF-beta2 on mucin MUC5AC protein
      and mRNA expression, and the impact of IL-13 on epithelial TGF-beta1, TGF-beta2,
      and MUC5AC were determined in cultured bronchial epithelial cells from
      endobronchial brushings of both subject groups. In biopsy tissue, epithelial TGF
      beta2 expression levels were higher than TGF-beta1 in both asthmatics and
      normals. TGF-beta2, but not TGF-beta1, was increased in asthmatics compared with
      normals, and significantly correlated with mucin expression. TGF-beta2, but not
      TGF-beta1, increased mucin expression in cultured epithelial cells from both
      subject groups. IL-13 increased the release of TGF-beta2, but not TGF-beta1, from
      epithelial cells. A neutralizing TGF-beta2 antibody partially inhibited IL-13
      induced mucin expression. These data suggest that TGF-beta2 production by
      asthmatic bronchial epithelial cells may increase airway mucin expression. IL-13
      induced mucin expression may occur in part through TGF-beta2 up-regulation.

PMID- 15466378
TI  - Transgenic mice overexpressing BMP4 develop a fibrodysplasia ossificans
      progressiva (FOP)-like phenotype.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary connective
      tissue disease characterized by progressive postnatal heterotopic bone formation.
      Although the genetic defects of FOP are not known, several lines of evidence have
      suggested that bone morphogenetic protein-4 (BMP4) may be involved in the
      pathophysiology. Nevertheless BMP4-transgenic mice have previously failed to
      develop the disorder and there has been no good animal model of the disease.
      Here, we report that a unique transgenic mouse line that overexpresses BMP4 under
      control of the neuron-specific enolase (NSE) promoter develops a FOP-like
      phenotype. Mating of these animals with transgenic animals that overexpress the
      BMP inhibitor noggin prevents the disorder, confirming the role of BMP4 in the
      pathogenesis of the disease. Heterotopic bone formation in these animals appears
      to follow the classic endochondral ossification pathway. Sex-mismatched cell
      transplantation experiments indicate that multiple cell sources contribute to the
      heterotopic ossification. This remarkable animal model provides a unique
      opportunity to further study the role of the BMP signaling pathway in heterotopic
      ossification and to improve our understanding of the clinical aspects of FOP.

PMID- 15466379
TI  - Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal
      CD56-/+dim chronic natural killer cell large granular lymphocytosis.
AB  - Indolent natural killer (NK) cell lymphoproliferative disorders include a
      heterogeneous group of patients in whom persistent expansions of mature,
      typically CD56(+), NK cells in the absence of any clonal marker are present in
      the peripheral blood. In the present study we report on the clinical,
      hematological, immunophenotypic, serological, and molecular features of a series
      of 26 patients with chronic large granular NK cell lymphocytosis, whose NK cells
      were either CD56(-) or expressed very low levels of CD56 (CD56(-/+dim) NK cells),
      in the context of an aberrant activation-related mature phenotype and proved to
      be monoclonal using the human androgen receptor gene polymerase chain reaction
      based assay. As normal CD56(+) NK cells, CD56(-/+dim) NK cells were granzyme
      B(+), CD3(-), TCRalphabeta/gammadelta(-), CD5(-), CD28(-), CD11a(+bright),
      CD45RA(+bright), CD122(+), and CD25(-) and they showed variable and heterogeneous
      expression of both CD8 and CD57. Nevertheless, they displayed several unusual
      immunophenotypic features. Accordingly, besides being CD56(-/+dim), they were
      CD11b(-/+dim) (heterogeneous), CD7(-/+dim) (heterogeneous), CD2(+) (homogeneous),
      CD11c(+bright) (homogeneous), and CD38(-/+dim) (heterogeneous). Moreover, CD56(
      /+dim) NK cells heterogeneously expressed HLA-DR. In that concerning the
      expression of killer receptors, CD56(-/+dim) NK cells showed bright and
      homogeneous CD94 expression, and dim and heterogeneous reactivity for CD161,
      whereas CD158a and NKB1 expression was variable. From the functional point of
      view, CD56(-/+dim) showed a typical Th1 pattern of cytokine production
      (interferon-gamma(+), tumor necrosis factor-alpha(+)). From the clinical point of
      view, these patients usually had an indolent clinical course, progression into a
      massive lymphocytosis with lung infiltration leading to death being observed in
      only one case. Despite this, they frequently had associated cytopenias as well as
      neoplastic diseases and/or viral infections. In summary, we describe a unique and
      homogeneous group of monoclonal chronic large granular NK cell lymphocytosis with
      an aberrant activation-related CD56(-/+dim)/CD11b(-/+dim) phenotype and an
      indolent clinical course, whose main clinical features are related to concomitant
      diseases.

PMID- 15466380
TI  - Tissue plasminogen activator in murine exocrine pancreas cancer: selective
      expression in ductal tumors and contribution to cancer progression.
AB  - Tissue plasminogen activator (tPA) is absent from normal human pancreas and is
      expressed in 95% of human pancreatic adenocarcinomas. We have analyzed the
      expression of components of the tPA system in murine pancreatic tumors and the
      role of tPA in neoplastic progression. Transgenic mice expressing T antigen and c
      myc under the control of the elastase promoter (Ela1-TAg and Ela1-myc,
      respectively) were used. tPA was undetectable in normal pancreas, acinar
      dysplasia, ductal complexes, and in all acinar tumors. By contrast, it was
      consistently detected in Ela1-myc tumors showing ductal differentiation. Crossing
      transgenic Ela1-myc with tPA-/- mice had no effect on the proportion of ductal
      tumors, indicating that tPA is not involved in the acinar-to-ductal transition.
      Ela1-myc:tPA-/- mice showed an increased survival in comparison to control mice.
      All ductal tumors, and none of the acinar tumors, overexpressed the tPA receptor
      annexin A2, suggesting its participation in the effects mediated by tPA. Our
      findings indicate that murine and human pancreatic ductal tumors share molecular
      alterations in the tPA system that may play a role in tumor progression.

PMID- 15466381
TI  - Deficient eosinophil chemotaxis-promoting activity of genetically normal mast
      cells transplanted into subcutaneous tissue of Mitfmi-vga9/Mitfmi-vga9 mice:
      comparison of the activity and mast cell distribution pattern with KitW/KitW
      vMice.
AB  - Despite the practical lack of mast cells in the skin tissue of WBB6F(1)
      Kit(W)/Kit(W-v), the skin tissue of WBB6F(1)-Mitf(mi-vga9)/Mitf(mi-vga9) mice
      contains one third of mast cells than that of WBB6F(1)-+/+ mice. We attempted to
      investigate the function of the decreased but appreciable number of mast cells in
      the skin of WBB6F(1)-Mitf(mi-vga9)/Mitf(mi-vga9) mice. The substance P (SP)
      induced eosinophil infiltration was examined using air-bleb assay. The air-bleb
      membrane was composed of the subcutaneous connective tissue. Unexpectedly, we
      found that the air-bleb membranes formed in the back of WBB6F(1)-Mitf(mi
      vga9)/Mitf(mi-vga9) mice contained no mast cells. The WBB6F(1)-Mitf(mi
      vga9)/Mitf(mi-vga9) mice showed impaired SP-induced eosinophil infiltration as
      observed in WBB6F(1)-Kit(W)/Kit(W-v) mice, indicating that mast cells detected in
      the dermis of WBB6F(1)-Mitf(mi-vga9)/Mitf(mi-vga9) mice did not help SP-induced
      eosinophil infiltration. Subcutaneous transplantation of cultured mast cells from
      WBB6F(1)-+/+ mice normalized SP-induced eosinophil infiltration in WBB6F(1)
      Kit(W)/Kit(W-v) mice but not in WBB6F(1)-Mitf(mi-vga9)/Mitf(mi-vga9) mice. The
      greater number and the more dispersed distribution pattern of mast cells that
      appeared in the subcutaneous connective tissue of WBB6F(1)-Kit(W)/Kit(W-v) mice
      after the transplantation appeared to explain the difference between WBB6F(1)
      Kit(W)/Kit(W-v) and WBB6F(1)-Mitf(mi-vga9)/Mitf(mi-vga9) mice.

PMID- 15466382
TI  - Aberrant methylation and down-regulation of TMS1/ASC in human glioblastoma.
AB  - TMS1/ASC is an intracellular signaling molecule with proposed roles in the
      regulation of apoptosis, nuclear factor-kappaB activation, and cytokine
      maturation. Previous studies have shown that TMS1/ASC is silenced by epigenetic
      means in human breast tumors. In this study, we examined methylation and
      expression of TMS1/ASC in glioblastoma multiforme (GBM). Whereas normal brain
      tissue was unmethylated at the TMS1 locus and expressed TMS1 message, 11 of 23
      human GBM cell lines exhibited reduced or absent expression of TMS1 that was
      associated with aberrant methylation of a CpG island in the promoter of the TMS1
      gene. Quantitative analysis showed that there was an inverse correlation between
      the degree of methylation and level of TMS1 expression. Treatment of GBM cell
      lines lacking TMS1 expression with the methyltransferase inhibitor 5-aza
      2'deoxycytidine resulted in partial demethylation and re-expression of TMS1.
      Analysis of primary tissues indicated that the TMS1 gene is unmethylated and
      expressed in normal brain, where its expression is restricted to astrocytes. In
      contrast, TMS1 was aberrantly methylated in 43% (10 of 23) primary GBM specimens.
      Tumors that exhibited aberrant methylation of TMS1 generally expressed reduced or
      absent expression of TMS1 as compared to unmethylated cases. Methylation of TMS1
      was not associated with patient age, gender, or treatment status. Although the
      relationship did not reach statistical significance, there was a trend toward
      increased overall survival for patients with unmethylated tumors. For one
      patient, disease progression from astrocytic astrocytoma (World Health
      Organization grade III) to GBM (World Health Organization grade IV) was
      associated with selective expansion of TMS1-negative cells. The data suggest a
      role for the epigenetic silencing of TMS1 in the pathogenesis of human GBM.
      Methylation of TMS1 may prove to be a useful prognostic marker and/or predictor
      of patient survival and tumor malignancy.

PMID- 15466383
TI  - Inhibition of hepatitis C virus nonstructural protein, helicase activity, and
      viral replication by a recombinant human antibody clone.
AB  - Hepatitis C virus (HCV) nonstructural protein 3 (NS3), with its protease,
      helicase, and NTPase enzymatic activities, plays a crucial role in viral
      replication, and therefore represents an ideal target for the development of anti
      viral agents. We have developed a recombinant human antibody (Fab) that reacts
      with the helicase domain of HCV NS3. The affinity-purified Fab antibody
      completely inhibited the helicase activity of HCV NS3 at equimolar concentration.
      To evaluate the effect of the Fab on HCV replication, the clone encoding the Fab
      gene was put into an expression vector, which converts Fab into a complete IgG1
      antibody. Using a DNA-based transfection model, we demonstrated that
      intracellular expression of this antibody resulted in significant reduction of
      HCV-negative strand RNA synthesis. Intracellular expression of this antibody into
      either a stable cell line replicating subgenomic RNA, or a transient full-length
      HCV replication model, reduced both HCV RNA and viral protein expression. These
      results support the use of recombinant antibody fragments to inhibit NS3 enzyme
      as a novel, feasible, and effective approach for inhibiting HCV replication.

PMID- 15466384
TI  - Cyclin-dependent kinase 5 is a regulator of podocyte differentiation,
      proliferation, and morphology.
AB  - Podocytes are highly specialized and terminally differentiated glomerular cells
      that play a vital role in renal physiology, including the prevention of
      proteinuria. Cyclin-dependent kinase 5 (CDK5) has been shown to influence several
      cellular processes in other terminally differentiated cells, in particular
      neurons. In this study, we examined the role of CDK5 in podocyte differentiation,
      proliferation, and morphology. In conditionally immortalized mouse podocytes in
      culture, CDK5 increased in association with podocyte differentiation. During
      mouse glomerulogenesis in vivo, CDK5 expression was predominantly detected in
      podocytes from the capillary loop stage to maturation and persisted in the
      podocytes of adult glomeruli. In contrast, CDK5 was markedly decreased in the
      proliferating and dedifferentiated podocytes of mice with anti-glomerular
      basement membrane nephritis and in human immunodeficiency virus transgenic mice.
      p35, the activator of CDK5, was also detected in podocytes and the p35/CDK5
      complex was active. Cell fractionation studies showed that active p35/CDK5 was
      mainly localized to the plasma membrane. Specific inhibition of CDK5 in
      differentiated cultured podocytes, either pharmacologically or with siRNA,
      induced shape changes, with cellular elongation and loss of process formation
      compared to the characteristic arborized phenotype. These data suggest a role for
      CDK5 as a regulator of podocyte differentiation, proliferation, and morphology.

PMID- 15466385
TI  - Expression of lymphangiogenic factors and evidence of intratumoral
      lymphangiogenesis in pancreatic endocrine tumors.
AB  - Lymphangiogenesis is thought to promote the progression of malignant tumors.
      Because the lymphangiogenic factors vascular endothelial factor (VEGF)-C and -D
      are expressed in endocrine cells, we investigated their expression in pancreatic
      endocrine tumors (PETs) and correlated these data and intratumoral lymph vessel
      density (iLVD) with clinicopathological features. Lymph vessels were identified
      with anti-podoplanin antiserum and with podoplanin/proliferating cell nuclear
      antigen double labeling. PETs (n = 104) were investigated by immunohistochemical
      staining for VEGF, basic fibroblast growth factor, and VEGF-C expression. VEGF-C
      and VEGF-D mRNA were quantified by real-time reverse transcriptase-polymerase
      chain reaction. PETs showed higher iLVD than normal pancreata, but iLVD did not
      discriminate between benign and malignant PETs. In PETs proliferating lymph
      vessels were identified. High iLVD was associated with lymph vessel invasion and
      it was more frequent in angioinvasive/metastatic tumors than in grossly invasive
      tumors. VEGF-C expression correlated with iLVD as well as with glucagon and
      pancreatic polypeptide expression. PETs show intratumoral lymphangiogenesis,
      which is associated with VEGF-C expression in tumor cells. The association
      between iLVD and lymph vessel invasion and angioinvasive/metastatic features in
      PETs suggests that lymphangiogenesis may promote malignant progression of PETs.
      PET is the first human tumor entity in which VEGF-C-related intratumoral
      lymphangiogenesis has been demonstrated.

PMID- 15466386
TI  - Impaired lung dendritic cell activation in CCR2 knockout mice.
AB  - Dendritic cell (DC) recruitment is a hallmark event in antigen (Ag)-challenged
      lungs. We previously reported models for analyzing DC migration and activation in
      the lung after Th1- or Th2-eliciting pathogen Ag-bead challenge. To determine the
      role of chemokines in DC mobilization, we applied this analysis to CCR1, CCR2,
      CCR5, and CCR6 chemokine receptor knockout mice. Both Mycobacteria bovis protein
      Ags and helminthic, Schistosoma mansoni egg Ags elicited multiple chemokines,
      including CCR1, CCR2, CCR5, and to a lesser extent CCR6 ligands. DCs from wild
      type lungs expressed transcripts for chemokine receptors, CCR1, CCR2, CCR5, and
      CXCR4. In all knockout strains, CD11c+ cells were recruited to Ag-beads likely
      because of receptor redundancy. However, DCs in CCR2-/- mice had significantly
      decreased MHCII and CD40 expression. This was associated with abrogated cytokine
      production in draining lymph node cultures. Analysis of local innate inflammation
      revealed a 50% reduction in macrophage recruitment in CCR2-/- mice. Bone marrow
      chimeras of mixed CCR2+/+ green fluorescent protein transgenic and CCR2-/- green
      fluorescent protein-negative cells confirmed the DC maturation defect was only
      among the latter population. In conclusion, CCR2 knockout confers an intrinsic DC
      activation defect and CCR2 ligands likely promote the local activation/maturation
      of inflammatory DCs.

PMID- 15466387
TI  - Role of CCR4 ligands, CCL17 and CCL22, during Schistosoma mansoni egg-induced
      pulmonary granuloma formation in mice.
AB  - Controversy persists pertaining to the role of CCR4 ligands, namely CCL17 (or
      thymus and activation regulated chemokine; TARC) and CCL22 (or macrophage-derived
      chemokine; MDC), in Th2-type cytokine-dominated responses in the lung.
      Accordingly, the present study addressed the relative role of each of these CC
      chemokines during an evolving pulmonary granulomatous response elicited by the
      intrapulmonary embolization of live Schistosoma mansoni eggs into S. mansoni
      sensitized mice. CCL22 protein expression peaked at day 4, but CCL17 levels were
      not increased significantly at any time after egg challenge. CCR4 transcript and
      protein expression were highest at day 8 after egg embolization and CCR4 protein
      was prominently expressed in macrophages surrounding S. mansoni eggs. Systemic
      immunoneutralization of CCL22 from the time of egg injection into S. mansoni
      sensitized mice for 8 days significantly decreased CCR4 protein expression, the
      eosinophil content, the overall size of the egg granuloma, and its hydroxyproline
      content. Whole lung levels of interferon-gamma were also significantly increased
      at day 8 in anti-CCL22-treated mice. The systemic immunoneutralization of CCL17
      had a lesser effect on all of the granuloma parameters listed above, but this
      antibody treatment significantly decreased granuloma hydroxyproline content to a
      greater extent than the anti-CCL22 antibody treatment. In addition, the
      immunoneutralization of CCL17 significantly increased whole lung levels of
      interleukin (IL)-4, IL-5, IL-13, transforming growth factor-beta, IL-12, and
      tumor necrosis factor-alpha at day 8 after egg infusion. Thus, these studies
      demonstrate a major role for CCL22 and a lesser role for CCL17 during an evolving
      S. mansoni egg granuloma in the lung.

PMID- 15466388
TI  - Smad3 deficiency ameliorates experimental obliterative bronchiolitis in a
      heterotopic tracheal transplantation model.
AB  - Chronic allograft rejection manifested as obliterative bronchiolitis (OB) remains
      the single greatest impediment to long-term survival after lung transplantation.
      Transforming growth factor-beta1 (TGF-beta1) has been implicated in the tissue
      remodeling response associated with OB. Therefore, its intracellular signal
      transducer, Smad3, is a prime target of investigation. Herein, we examine the
      role of TGF-beta1, through Smad3, in the development of OB using heterotopic
      tracheal transplantation in wild-type and Smad3-null mice. TGF-beta1 was
      detectable within infiltrating mononuclear cells early after transplantation.
      Later it was detected in fibroblasts and in the connective tissue accumulating
      within the lumen and the airway wall of the transplanted allografts. Connective
      tissue growth factor had a similar time and tissue distribution. Nuclear
      detection of Smad3 and phosphorylated Smads within intraluminal fibroblasts
      coincided with increased intraluminal deposition of fibronectin and collagen.
      When transplanted into Smad3-null mice, allografts failed to organize the
      intraluminal exudates despite fibroblast accumulation and showed reduced
      fibronectin and collagen deposition. In culture, Smad3-deficient fibroblasts
      expressed reduced fibronectin in response to TGF-beta1 compared to wild-type
      cells. Together, these studies suggest that the TGF-beta signal transducer,
      Smad3, is required for the development of experimental OB in transplanted
      tracheas.

PMID- 15466389
TI  - Activated hepatic stellate cells express keratinocyte growth factor in chronic
      liver disease.
AB  - Keratinocyte growth factor (KGF), a member of the fibroblast growth factor (FGF)
      family, is a specific mitogen for different types of epithelial cells and a
      potent survival factor for these cells under stress conditions. KGF expression
      increases strongly after injury to various tissues, including the skin and the
      intestine, and signaling via the KGF receptor was shown to be crucial for repair
      of skin wounds and for liver regeneration. Here we demonstrate an increased
      expression of KGF in chronic liver disease associated with fibrosis. The extent
      of KGF overexpression correlated strongly with the stage of fibrosis. As the
      cellular source of KGF we identified activated hepatic stellate cells
      (HSCs)/myofibroblasts. In contrast to the ligand, the KGF receptor, FGFR2-IIIb,
      was exclusively expressed by hepatocytes, but not by activated HSCs or other
      parenchymal or nonparenchymal liver cells. Based on the known effects of KGF on
      hepatocytes in vitro, our findings suggest that HSC/myofibroblast-derived KGF may
      enhance liver regeneration and/or hepatocyte survival in patients with chronic
      liver disease.

PMID- 15466390
TI  - Urinary excretion of fatty acid-binding protein reflects stress overload on the
      proximal tubules.
AB  - Urinary excretion of human liver-type fatty acid-binding protein (hL-FABP), which
      is expressed in human proximal tubules and engaged in free fatty acid (FFA)
      metabolism, was reported to reflect the clinical prognosis of chronic kidney
      disease. Here we have investigated the pathophysiological significance of hL-FABP
      in a model of protein overload nephropathy. Because L-FABP is not expressed in
      the wild-type mice, we generated hL-FABP chromosomal gene transgenic (Tg) mice.
      Tg mice were intraperitoneally injected with bovine serum albumin (BSA) replete
      with FFAs (r-BSA group) or FFA-depleted BSA (d-BSA group). The r-BSA group
      developed significantly more severe tubulointerstitial damage than did the d-BSA
      group. Renal expression of the hL-FABP gene was more up-regulated, and urinary
      excretion of hL-FABP was significantly higher, in the r-BSA group than in the d
      BSA group. Furthermore, compared with their wild-type littermates injected with r
      BSA, the number of infiltrated macrophages was significantly attenuated in Tg
      mice injected with it on day 28. In patients with kidney disease (n = 50),
      urinary hL-FABP was correlated with both urinary protein and the severity of
      tubulointerstitial injury. In conclusion, our experimental model suggests that
      urinary excretion of hL-FABP reflects stresses, such as urinary protein overload,
      on the proximal tubules. The clinical observations support this hypothesis.

PMID- 15466391
TI  - CD4+CD45RBHi interleukin-4 defective T cells elicit antral gastritis and
      duodenitis.
AB  - We have analyzed the gastrointestinal inflammation which develops following
      adoptive transfer of IL-4 gene knockout (IL-4(-/-)) CD4(+)CD45RB(Hi) (RB(Hi)) T
      cells to severe combined immunodeficient (SCID) or to T cell-deficient, T cell
      receptor beta and delta double knockout (TCR(-/-)) mice. Transfer of IL-4(-/-)
      RB(Hi) T cells induced a similar type of colitis to that seen in SCID or TCR(-/-)
      recipients of wild-type (wt) RB(Hi) T cells as reported previously.
      Interestingly, transfer of both wt and IL-4(-/-) RB(Hi) T cells to TCR(-/-) but
      not to SCID mice induced inflammation in the gastric mucosa. Notably, TCR(-/-)
      recipients of IL-4(-/-) RB(Hi) T cells developed a more severe gastritis with
      erosion, apoptosis of the antral epithelium, and massive infiltration of
      macrophages. This gastritis was partially dependent on the indigenous microflora.
      Recipients of both wt and IL-4(-/-) RB(Hi) T cells developed duodenitis with
      multinuclear giant cells, expansion of mucosal macrophages, and dendritic cells.
      Full B cell responses were reconstituted in TCR(-/-) recipients of RB(Hi) T
      cells; however, anti-gastric autoantibodies were not detected. We have now
      developed and characterized a novel model of chronic gastroduodenitis in mice,
      which will help in our understanding of the mechanisms involved in chronic
      inflammation in the upper gastrointestinal tract of humans.

PMID- 15466392
TI  - A novel in vivo lecithin-cholesterol acyltransferase (LCAT)-deficient mouse
      expressing predominantly LpX is associated with spontaneous glomerulopathy.
AB  - Complete lecithin cholesterol acyltransferase (LCAT) deficiency is a rare genetic
      cause of extreme reduction in high density lipoproteins and there is a high
      prevalence of chronic renal dysfunction that may progress to renal failure.
      Previous in vitro studies suggest the vesicular lipoprotein X (LpX) particles
      commonly seen in LCAT-deficient plasmas may be causative. To test this
      hypothesis, we have generated a novel murine model that selectively accumulate
      LpX in the circulation by cross breeding the sterol regulatory element binding
      protein (SREBP) 1a transgenic mice (S+) with the LCAT knockout (lcat-/-) mice.
      Fast protein liquid chromatography fractionation of pooled plasma lipids revealed
      that virtually all cholesterol is concentrated in the very low density
      lipoprotein (VLDL)-sized fractions. These fractions are enriched in free
      cholesterol and phospholipid but extremely poor in triglyceride. Electron
      microscopy of the d <1.063 g/ml fraction of the S+lcat-/- mice revealed abnormal
      large vesicular particles, suggestive of LpX. The S+lcat-/- mice developed
      glomerular lesions spontaneously evident at 6 months with glomerular and
      tubulointerstitial lipid-deposits. Immunohistochemical staining with RhoA showed
      marked positive focal staining in glomeruli in the S+lcat-/- mice and
      undetectable in the S+/lcat+/+ control. By 10 months of age, the kidneys showed
      progressive glomerular injury including segmental foam cell infiltrates,
      mesangial expansion, and hyalinosis. Renal abnormalities are very similar to
      those seen in human LCAT deficiency. We conclude that the selective high-level
      accumulation of plasma LpX in the S+lcat-/- mice is strongly associated with a
      spontaneous glomerulopathy, providing in vivo evidence that LpX contributes to
      the LCAT deficiency-related nephropathy.

PMID- 15466393
TI  - The 150-kilodalton oxygen-regulated protein ameliorates lipopolysaccharide
      induced acute lung injury in mice.
AB  - The 150-kd oxygen-regulated protein is a novel stress protein that is located in
      the endoplasmic reticulum and contributes to cell survival when this organelle is
      under stress. Expression of this protein was strongly increased in alveolar
      macrophages and alveolar epithelial cells from mice with acute lung injury
      induced by lipopolysaccharide. Transgenic mice overexpressing the 150-kd protein
      showed decreased histological severity of this lung injury, accompanied by lower
      total protein concentrations, and lactate dehydrogenase activity in
      bronchoalveolar lavage fluid. As indicated by nick end-labeling,
      lipopolysaccharide induced apoptosis in fewer alveolar wall cells in transgenic
      than in wild-type mice. Transgenic mice also showed increased survival after
      lipopolysaccharide injection (a log-rank test). Thus, the 150-kd protein, an
      endoplasmic reticulum-related molecular chaperone, is pivotal in resisting acute
      lung injury from lipopolysaccharide.

PMID- 15466394
TI  - Massive CA1/2 neuronal loss with intraneuronal and N-terminal truncated Abeta42
      accumulation in a novel Alzheimer transgenic model.
AB  - Alzheimer's disease (AD) is characterized by a substantial degeneration of
      pyramidal neurons and the appearance of neuritic plaques and neurofibrillary
      tangles. Here we present a novel transgenic mouse model, APP(SL)PS1KI that
      closely mimics the development of AD-related neuropathological features including
      a significant hippocampal neuronal loss. This transgenic mouse model carries
      M233T/L235P knocked-in mutations in presenilin-1 and overexpresses mutated human
      beta-amyloid (Abeta) precursor protein. Abeta(x-42) is the major form of Abeta
      species present in this model with progressive development of a complex pattern
      of N-truncated variants and dimers, similar to those observed in AD brain. At 10
      months of age, an extensive neuronal loss (>50%) is present in the CA1/2
      hippocampal pyramidal cell layer that correlates with strong accumulation of
      intraneuronal Abeta and thioflavine-S-positive intracellular material but not
      with extracellular Abeta deposits. A strong reactive astrogliosis develops
      together with the neuronal loss. This loss is already detectable at 6 months of
      age and is PS1KI gene dosage-dependent. Thus, APP(SL)PS1KI mice further confirm
      the critical role of intraneuronal Abeta(42) in neuronal loss and provide an
      excellent tool to investigate therapeutic strategies designed to prevent AD
      neurodegeneration.

PMID- 15466395
TI  - Desmin ensheathment ratio as an indicator of vessel stability: evidence in normal
      development and in retinopathy of prematurity.
AB  - We developed a measure of pericyte/endothelial interaction, the desmin
      ensheathment ratio (DER), using the intermediate filament desmin as an indicator
      of pericyte ensheathment and have examined the DER in normal retinal vascular
      development and in the kitten retinopathy of prematurity (ROP) model. We also
      examined the role of mural cells in the pathogenesis of ROP. Postnatal day 1 to
      45 kitten retinae were labeled for desmin, alpha-smooth muscle actin (SMA), and
      isolectin-B4. Newborn kittens exposed to hyperoxia and then returned to room air
      for 0 to 40 days (dRA) were similarly labeled. The ratio of desmin to lectin
      labeling on confocal images yielded the DER. Ultrastructural studies showed that
      mural cells were present on even the most primitive vessels. During normal
      development, immature vascular beds had DERs of 0.3 to 0.6 whereas mature beds,
      which predominated by postnatal day 28, had DERs greater than 0.9. Immature
      pericytes and smooth muscle cells did not prevent hyperoxia-induced vessel
      regression. During the vasoproliferative stage of ROP, the DERs of intra- and
      preretinal vessels ranged between 0.2 and 0.5. In the recovery stage, the DER
      increased in parallel with regression of pathology, reaching 0.9 at 34 dRA.
      Stabilization of the DER by the fifth postnatal week was temporally coincident
      with the development of resistance to hyperoxia-induced vessel regression
      previously reported in the kitten. These observations lead us to suggest that a
      DER of 0.9 represents a vascular stability threshold and that a low DER observed
      during ROP raises the possibility that mural cell abnormalities play a key role
      in the pathogenesis of ROP.

PMID- 15466396
TI  - Adhesion-mediated squamous cell carcinoma survival through ligand-independent
      activation of epidermal growth factor receptor.
AB  - The survival and growth of squamous epithelial cells require signals generated by
      integrin-matrix interactions. After conversion to squamous cell carcinoma, the
      cells remain sensitive to detachment-induced anoikis, yet in tumor cell
      aggregates, which are matrix-deficient, these cells are capable of suprabasal
      survival and proliferation. Their survival is enhanced through a process we call
      synoikis, whereby junctional adhesions between neighboring cells generate
      specific downstream survival signals. Here we show that in squamous cell
      carcinoma cells, E-cadherin-mediated cell-cell contacts specifically induce
      activation of epidermal growth factor receptor (EGFR). EGFR activation in turn
      triggers the ERK/MAPK signaling module, leading to elevation of anti-apoptotic
      Bcl-2. After intercellular adhesion, formation of adherens junctions triggers the
      formation of E-cadherin-EGFR complexes, correlating with EGFR transactivation.
      Analysis of the process with a dominant-negative EGFR mutant indicated that
      activation of EGFR is ligand-independent. Our data implicate cell-cell adhesion
      induced activation of EGFR as a cooperative mechanism that generates compensatory
      survival signaling, protecting malignant cells from detachment-induced death.

PMID- 15466397
TI  - Hyaluronan participates in the epidermal response to disruption of the
      permeability barrier in vivo.
AB  - Hyaluronan (hyaluronic acid, HA) is a glycosaminoglycan in the extracellular
      matrix of tissues that plays a role in cellular migration, proliferation and
      differentiation. Injury to the stratum corneum elicits an epidermal
      hyperproliferative response, a pathogenic feature in many cutaneous diseases
      including eczema and psoriasis. Because HA is abundant in the matrix between
      keratinocytes, we asked whether the presence of HA is required for epidermal
      hyperplasia to occur in response to barrier injury. Disruption of the stratum
      corneum, by acetone application on the skin of hairless mice, led to a marked
      accumulation of HA in the matrix between epidermal basal and spinous
      keratinocytes, and also within keratinocytes of the upper epidermis. To test
      whether HA may have a functional role in epidermal hyperplasia, we used
      Streptomyces hyaluronidase (StrepH), delivered topically, to degrade epidermal HA
      and blunt the accumulation of epidermal HA after acetone. StrepH signficantly
      reduced epidermal HA levels, and also significantly inhibited the development of
      epidermal hyperplasia. This reduction in epidermal thickness was not attributable
      to any decrease in keratinocyte proliferation, but rather to an apparent
      acceleration in terminal differentiation (ie, increased keratin 10 and filaggrin
      expression). Overall, the data show that HA is a significant participant in the
      epidermal response to barrier injury.

PMID- 15466398
TI  - Pbx3 deficiency results in central hypoventilation.
AB  - Pbx proteins comprise a family of TALE (three amino acid loop extension) class
      homeodomain transcription factors that are implicated in developmental gene
      expression through their abilities to form hetero-oligomeric DNA-binding
      complexes and function as transcriptional regulators in numerous cell types. We
      demonstrate here that one member of this family, Pbx3, is expressed at high
      levels predominantly in the developing central nervous system, including a region
      of the medulla oblongata that is implicated in the control of respiration. Pbx3
      deficient mice develop to term but die within a few hours of birth from central
      respiratory failure due to abnormal activity of inspiratory neurons in the
      medulla. This partially phenocopies the defect in mice deficient for Rnx, a
      metaHox homeodomain transcription factor, that we demonstrate here is capable of
      forming a DNA-binding complex with Pbx3. Rnx expression is unperturbed in Pbx3
      deficient mice, but its ability to enhance transcription in vitro as a complex
      with TALE proteins is compromised in the absence of Pbx3. Thus, Pbx3 is essential
      for respiration and, like its DNA-binding partner Rnx, is critical for proper
      development of medullary respiratory control mechanisms. Pbx3-deficient mice
      provide a model for congenital central hypoventilation syndrome and suggest that
      Pbx3 mutations may promote the pathogenesis of this disorder.

PMID- 15466399
TI  - Overexpression of the replication licensing regulators hCdt1 and hCdc6
      characterizes a subset of non-small-cell lung carcinomas: synergistic effect with
      mutant p53 on tumor growth and chromosomal instability--evidence of E2F-1
      transcriptional control over hCdt1.
AB  - Replication licensing ensures once per cell cycle replication and is essential
      for genome stability. Overexpression of two key licensing factors, Cdc6 and Cdt1,
      leads to overreplication and chromosomal instability (CIN) in lower eukaryotes
      and recently in human cell lines. In this report, we analyzed hCdt1, hCdc6, and
      hGeminin, the hCdt1 inhibitor expression, in a series of non-small-cell lung
      carcinomas, and investigated for putative relations with G(1)/S phase regulators,
      tumor kinetics, and ploidy. This is the first study of these fundamental
      licensing elements in primary human lung carcinomas. We herein demonstrate
      elevated levels (more than fourfold) of hCdt1 and hCdc6 in 43% and 50% of
      neoplasms, respectively, whereas aberrant expression of hGeminin was observed in
      49% of cases (underexpression, 12%; overexpression, 37%). hCdt1 expression
      positively correlated with hCdc6 and E2F-1 levels (P = 0.001 and P = 0.048,
      respectively). Supportive of the observed link between E2F-1 and hCdt1, we
      provide evidence that E2F-1 up-regulates the hCdt1 promoter in cultured mammalian
      cells. Interestingly, hGeminin overexpression was statistically related to
      increased hCdt1 levels (P = 0.025). Regarding the kinetic and ploidy status of
      hCdt1- and/or hCdc6-overexpressing tumors, p53-mutant cases exhibited
      significantly increased tumor growth values (Growth Index; GI) and aneuploidy/CIN
      compared to those bearing intact p53 (P = 0.008 for GI, P = 0.001 for CIN). The
      significance of these results was underscored by the fact that the latter
      parameters were independent of p53 within the hCdt1-hCdc6 normally expressing
      cases. Cumulatively, the above suggest a synergistic effect between hCdt1-hCdc6
      overexpression and mutant-p53 over tumor growth and CIN in non-small-cell lung
      carcinomas.

PMID- 15466400
TI  - Two closely related ubiquitin C-terminal hydrolase isozymes function as
      reciprocal modulators of germ cell apoptosis in cryptorchid testis.
AB  - The experimentally induced cryptorchid mouse model is useful for elucidating the
      in vivo molecular mechanism of germ cell apoptosis. Apoptosis, in general, is
      thought to be partly regulated by the ubiquitin-proteasome system. Here, we
      analyzed the function of two closely related members of the ubiquitin C-terminal
      hydrolase (UCH) family in testicular germ cell apoptosis experimentally induced
      by cryptorchidism. The two enzymes, UCH-L1 and UCH-L3, deubiquitinate ubiquitin
      protein conjugates and control the cellular balance of ubiquitin. The testes of
      gracile axonal dystrophy (gad) mice, which lack UCH-L1, were resistant to
      cryptorchid stress-related injury and had reduced ubiquitin levels. The level of
      both anti-apoptotic (Bcl-2 family and XIAP) and prosurvival (pCREB and BDNF)
      proteins was significantly higher in gad mice after cryptorchid stress. In
      contrast, Uchl3 knockout mice showed profound testicular atrophy and apoptotic
      germ cell loss after cryptorchid injury. Ubiquitin level was not significantly
      different between wild-type and Uchl3 knockout mice, whereas the levels of Nedd8
      and the apoptotic proteins p53, Bax, and caspase3 were elevated in Uchl3 knockout
      mice. These results demonstrate that UCH-L1 and UCH-L3 function differentially to
      regulate the cellular levels of anti-apoptotic, prosurvival, and apoptotic
      proteins during testicular germ cell apoptosis.

PMID- 15466401
TI  - Overexpression of human matrix metalloproteinase-12 enhances the development of
      inflammatory arthritis in transgenic rabbits.
AB  - Increased proteolytic activity of matrix metalloproteinases (MMPs) may promote
      articular destruction such as occurs in rheumatoid arthritis and osteoarthritis.
      Recently, we reported that synovial tissue and fluid obtained from patients with
      rheumatoid arthritis contained higher activity of macrophage elastase (MMP-12).
      To examine the hypothesis that MMP-12 may potentially enhance the progression of
      arthritis, we investigated the effects of overexpression of MMP-12 on
      inflammatory arthritis in transgenic rabbits that express the human MMP-12
      transgene in the macrophage lineage. Inflammatory arthritis was produced by
      articular injection of carrageenan solution and the degree of inflammatory
      arthritis in transgenic rabbits was compared with that in control rabbits. We
      found that overexpression of MMP-12 in transgenic rabbits significantly enhanced
      the arthritic lesions, resulting in severe synovial thickening, pannus formation,
      and prominent macrophage infiltration at an early stage and a marked destruction
      of articular cartilage associated with loss of proteoglycan at a later stage.
      These results demonstrate that excessive MMP-12 expression exacerbates articular
      connective tissue and cartilage degradation and thus plays a critical role in the
      development of inflammatory joint disease.

PMID- 15466402
TI  - Homocysteine, system b0,+ and the renal epithelial transport and toxicity of
      inorganic mercury.
AB  - Proximal tubular epithelial cells are major sites of homocysteine (Hcy)
      metabolism and are the primary sites for the accumulation and intoxication of
      inorganic mercury (Hg(2+)). Previous in vivo data from our laboratory have
      demonstrated that mercuric conjugates of Hcy are transported into these cells by
      unknown mechanisms. Recently, we established that the mercuric conjugate of
      cysteine [2-amino-3-(2-amino-2-carboxy-ethylsulfanylmercuricsulfanyl)propionic
      acid; Cys-S-Hg-S-Cys], is transported by the luminal, amino acid transporter,
      system b(0,+). As Cys-S-Hg-S-Cys and the mercuric conjugate of Hcy (2-amino-4-(3
      amino-3-carboxy-propylsulfanylmercuricsulfanyl)butyric acid; Hcy-S-Hg-S-Hcy) are
      similar structurally, we hypothesized that Hcy-S-Hg-S-Hcy is a substrate for
      system b(0,+). To test this hypothesis, we analyzed the saturation kinetics, time
      dependence, temperature dependence, and substrate specificity of Hcy-S-Hg-S-Hcy
      transport in Madin-Darby canine kidney (MDCK) cells stably transfected with
      system b(0,+). MDCK cells are good models in which to study this transport
      because they do not express system b(0,+). Uptake of Hg(2+) was twofold greater
      in the transfectants than in wild-type cells. Moreover, the transfectants were
      more susceptible to the toxic effects of Hcy-S-Hg-S-Hcy than wild-type cells.
      Accordingly, our data indicate that Hcy-S-Hg-S-Hcy is transported by system
      b(0,+) and that this transporter likely plays a role in the nephropathy induced
      after exposure to Hg(2+). These data are the first to implicate a specific,
      luminal membrane transporter in the uptake and toxicity of mercuric conjugates of
      Hcy in any epithelial cell.

PMID- 15466403
TI  - Molecular genetic evidence for different clonal origins of epithelial and stromal
      components of phyllodes tumor of the prostate.
AB  - Phyllodes tumor of the prostate is a rare neoplasm, composed of epithelium-lined
      cysts and channels embedded in a variably cellular stroma. The pathogenetic
      relationship of the epithelium and stroma is unknown and whether each is a clonal
      neoplastic element is uncertain. We studied the clonality of phyllodes tumors
      from six patients who underwent either enucleation or transurethral resection as
      their initial treatment. This was followed by total prostatectomy in three of the
      patients. Laser-assisted microdissection was performed to extract epithelial and
      stromal components of phyllodes tumor from formalin-fixed, paraffin-embedded
      tissue. Polymerase chain reaction was used to amplify genomic DNA at specific
      loci on chromosome 7q31 (D7S522), 8p21.3-q11.1 (D8S133, D8S137), 8p22 (D8S261),
      10q23 (D10S168, D10S571), 17p13 (TP53), 16q23.2 (D16S507), 12q11-12 (D12S264),
      17q (D17S855), 18p11.22-p11 (D18S53), and 22q11.2 (D22S264). In each tumor,
      stroma and epithelium were analyzed separately. Gel electrophoresis with
      autoradiography was used to detect loss of heterozygosity. All tumors showed
      allelic loss in one or more loci of both the epithelial and stromal components.
      The frequency of allelic loss in the epithelial component was 2 of 5 (40%) at
      D7S522, 2 of 6 (33%) at D8S133, 1 of 5 (20%) at D8S137, 3 of 6 (50%) at D8S261, 4
      of 4 (100%) at D10S168, 4 of 6 (67%) at TP53, 2 of 6 (33%) at D10S571, 6 of 6
      (100%) at D16S507, 1 of 5 (20%) at D12S264, 1 of 6 (17%) at D17S855, 2 of 6 (33%)
      at D18S53, and 2 of 5 (40%) at D22S264. The frequency of allelic loss in the
      stromal component was 2 of 5 (40%) at D7S522, 1 of 6 (17%) at D8S133, 2 of 5
      (40%) at D8S137, 3 of 6 (50%) at D8S261, 1 of 4 (25%) at D10S168, 3 of 6 (50%) at
      TP53, 2 of 6 (33%) at D10S571, 3 of 6 (50%) at D16S507, 1 of 5 (20%) at D12S264,
      0 of 6 (0%) at D17S855, 1 of 6 (17%) at D18S53, and 0 of 5 (0%) at D22S264. The
      pattern of allelic loss is significantly different in both stroma and epithelium
      statistically; completely concordant allelic loss patterns were not seen in any
      tumor examined. Our data demonstrate that both epithelial and stromal components
      of phyllodes tumor of the prostate are clonal, supporting the hypothesis that
      both elements are neoplastic. While both epithelium and stroma are clonal
      proliferations, they appear to have different clonal origins.

PMID- 15466404
TI  - The tubulin-binding agent combretastatin A-4-phosphate arrests endothelial cells
      in mitosis and induces mitotic cell death.
AB  - The tubulin-binding agent combretastatin A-4-phosphate (CA-4-P), rapidly disrupts
      the vascular network of tumors leading to secondary tumor cell death. In vitro,
      CA-4-P destabilizes microtubules and causes endothelial cell death. In this study
      we analyze the mechanisms by which CA-4-P induces the death of proliferating
      endothelial cells. We demonstrate that at >/=7.5 nmol/L, CA-4-P damages mitotic
      spindles, arrests cells at metaphase, and leads to the death of mitotic cells
      with characteristic G(2)/M DNA content. Mitotic arrest was associated with
      elevated levels of cyclin B1 protein and p34(cdc2) activity. Inhibition of
      p34(cdc2) activity by purvalanol A caused mitotic-arrested cells to rapidly exit
      mitosis, suggesting that sustained p34(cdc2) activity was responsible for
      metaphase arrest. Pharmacological prevention of entry into mitosis protected
      cells from undergoing cell death, further establishing the link between mitosis
      and cell death induction by CA-4-P. CA-4-P-mediated cell death shared
      characteristics of apoptosis but was independent of caspase activation suggesting
      the involvement of a non-caspase pathway(s). These data suggest that induction of
      apoptosis in endothelial cells by CA-4-P is associated with prolonged mitotic
      arrest. Therefore, by activating cell death pathways, CA-4-P, in addition to
      being an effective anti-vascular agent, may also interfere with regrowth of blood
      vessels in the tumor.

PMID- 15466405
TI  - ApoAI deficiency results in marked reductions in plasma cholesterol but no
      alterations in amyloid-beta pathology in a mouse model of Alzheimer's disease
      like cerebral amyloidosis.
AB  - Epidemiological studies suggest links between cholesterol metabolism and
      Alzheimer's disease (AD), with hypercholesterolemia associated with increased AD
      risk, and use of cholesterol-lowering drugs associated with decreased risk.
      Animal models using cholesterol-modifying dietary or pharmacological
      interventions demonstrate similar findings. Proposed mechanisms include effects
      of cholesterol on the metabolism of amyloid-beta (Abeta), the protein that
      deposits in AD brain. To investigate the effect of genetic alterations in plasma
      cholesterol on Abeta pathology, we crossed the PDAPP transgenic mouse model of AD
      like cerebral amyloidosis to apolipoprotein AI-null mice that have markedly
      reduced plasma cholesterol levels due to a virtual absence of high density
      lipoproteins, the primary lipoprotein in mice. Interestingly and in contrast to
      models using non-physiological high fat diets or cholesterol-lowering drugs to
      modify plasma cholesterol, we observed no differences in Abeta pathology in PDAPP
      mice of the various apoAI genotypes despite robust differences in plasma
      cholesterol levels between the groups. Absence of apoAI also resulted in
      reductions in brain but not cerebrospinal fluid cholesterol, but had no effect on
      brain apolipoprotein E levels. These and other data suggest that it is perhaps
      the level of brain apolipoprotein E, not cholesterol per se, that plays a primary
      role in brain Abeta metabolism.

PMID- 15466406
TI  - FLICE-like inhibitory protein (FLIP) protects against apoptosis and suppresses NF
      kappaB activation induced by bacterial lipopolysaccharide.
AB  - Bacterial lipopolysaccharide (LPS) via its activation of Toll-like receptor-4
      contributes to much of the vascular injury/dysfunction associated with gram
      negative sepsis. Inhibition of de novo gene expression has been shown to
      sensitize endothelial cells (EC) to LPS-induced apoptosis, the onset of which
      correlates with decreased expression of FLICE-like inhibitory protein (FLIP). We
      now have data that conclusively establish a role for FLIP in protecting EC
      against LPS-induced apoptosis. Overexpression of FLIP protected against LPS
      induced apoptosis, whereas down-regulation of FLIP using antisense
      oligonucleotides sensitized EC to direct LPS killing. Interestingly, FLIP
      overexpression suppressed NF-kappaB activation induced by LPS, but not by phorbol
      ester, suggesting a specific role for FLIP in mediating LPS activation.
      Conversely, mouse embryo fibroblasts (MEF) obtained from FLIP -/- mice showed
      enhanced LPS-induced NF-kappaB activation relative to those obtained from wild
      type mice. Reconstitution of FLIP-/- MEF with full-length FLIP reversed the
      enhanced NF-kappaB activity elicited by LPS in the FLIP -/- cells. Changes in the
      expression of FLIP had no demonstrable effect on other known LPS/Tlr-4-activated
      signaling pathways including the p38, Akt, and Jnk pathways. Together, these data
      support a dual role for FLIP in mediating LPS-induced apoptosis and NF-kappaB
      activation.

PMID- 15466407
TI  - A protein C deficiency exacerbates inflammatory and hypotensive responses in mice
      during polymicrobial sepsis in a cecal ligation and puncture model.
AB  - During the systemic inflammatory state induced by sepsis, the potential for
      coagulopathy exists because of up-regulation of natural procoagulants and anti
      fibrinolytics, and down-regulation of natural anti-coagulants, with protein C
      (PC) being a critical example of the latter case. PC functions as an anti
      coagulant, profibrinolytic, and anti-inflammatory agent, and, thus, its
      administration or deficiency may affect the course and outcome of sepsis in
      patients. In this study, a cecal ligation and puncture model of septic
      peritonitis was applied to wild-type mice and littermates with a targeted
      heterozygous deficiency of PC (PC(+/-)) to characterize the importance of a PC
      deficiency on polymicrobial sepsis. An enhanced mortality rate was found to
      accompany a PC deficiency. Plasma cytokines, as well as organ-specific expression
      of cytokine transcripts, were elevated in PC(+/-) mice. No signs of severe
      disseminated intravascular coagulation (DIC) were observed in wild-type or PC(+/
      ) mice, as indicated by an increase in fibrinogen levels and the invariability of
      platelet counts after cecal ligation and puncture. Consumption of coagulation
      factors was similar in both genotypes and a decrease in the PC mRNA and protein
      levels was more prominent in PC(+/-) mice. Renal and organ muscle damage was
      enhanced in PC(+/-) mice, as shown by increases in plasma blood urea nitrogen,
      creatinine, and creatinine kinase. Hypotension and bradycardia were more enhanced
      in PC(+/-) mice than in wild-type mice, thus provoking a more severe septic shock
      response. Thus, the hemodynamic role of PC during sepsis is of critical
      importance to the outcome of the disease.

PMID- 15466408
TI  - The cortical microtubule array: from dynamics to organization.

PMID- 15466409
TI  - Vernalization, competence, and the epigenetic memory of winter.

PMID- 15466411
TI  - A role for nuclear factor I in the intrinsic control of cerebellar granule neuron
      gene expression.
AB  - Nervous system formation requires the elaboration of a complex series of
      differentiation events in both a spatially and maturation-regulated manner. A
      fundamental question is how neuronal subtype specification and developmental gene
      expression are controlled within maturing neurons. The alpha6 subunit of the
      gamma-aminobutyric acid type A (GABA(A)) receptor (GABRA6) is preferentially
      expressed in cerebellar granule neurons and is part of an intrinsic program
      directing their differentiation. We have employed a lentiviral approach to
      examine the transcriptional mechanisms controlling neuronal subtype-selective
      expression of this gene. These studies demonstrated that nuclear factor I (NFI)
      proteins are required for both transgenic GABRA6 promoter activity as well as
      endogenous expression of this gene in cerebellar granule neurons. Chromatin
      immunoprecipitation also showed that NFI proteins are bound to the GABRA6
      promoter in these cells in vivo. Furthermore, analyses of gene knockout mice
      revealed that Nfia is specifically required for normal expression of the GABRA6
      gene in cerebellar granule neurons. NFI expression and DNA binding activity are
      highly enriched in granule neurons, implicating this transcription factor family
      in the neuronal subtype-selective expression of the GABRA6 gene. These studies
      define a new role for NFI proteins as neuronal subtype-enriched transcriptional
      regulators that participate in an intrinsic transcriptional program directing the
      differentiation of cerebellar granule neurons.

PMID- 15466410
TI  - Repeated evolution of the pyrrolizidine alkaloid-mediated defense system in
      separate angiosperm lineages.
AB  - Species of several unrelated families within the angiosperms are able to
      constitutively produce pyrrolizidine alkaloids as a defense against herbivores.
      In pyrrolizidine alkaloid (PA) biosynthesis, homospermidine synthase (HSS)
      catalyzes the first specific step. HSS was recruited during angiosperm evolution
      from deoxyhypusine synthase (DHS), an enzyme involved in the posttranslational
      activation of eukaryotic initiation factor 5A. Phylogenetic analysis of 23 cDNA
      sequences coding for HSS and DHS of various angiosperm species revealed at least
      four independent recruitments of HSS from DHS: one within the Boraginaceae, one
      within the monocots, and two within the Asteraceae family. Furthermore, sequence
      analyses indicated elevated substitution rates within HSS-coding sequences after
      each gene duplication, with an increased level of nonsynonymous mutations.
      However, the contradiction between the polyphyletic origin of the first enzyme in
      PA biosynthesis and the structural identity of the final biosynthetic PA products
      needs clarification.

PMID- 15466412
TI  - T-cell activation leads to poor activation of the HIV-1 clade E long terminal
      repeat and weak association of nuclear factor-kappaB and NFAT with its enhancer
      region.
AB  - The enhancer region in the human immunodeficiency virus type 1 (HIV-1) 5'-long
      terminal repeat (LTR) is very important for viral transcription. This promoter
      sequence binds both nuclear factor-kappaB and NFAT, two important modulators of
      HIV-1 gene expression. Previous studies have indicated that the enhancer regions
      of the different HIV-1 clade LTRs differ in their number of NF-kappaB-binding
      sites. In this study, we have compared the activation potential of the different
      HIV-1 clade and HIV-2 LTRs and assessed their interaction with NFAT and NF
      kappaB. In T-cell lines and primary CD4(+) T-cells, the results showed that the
      HIV-1 clade E LTR (with a single NF-kappaB-binding site) was the weakest LTR
      regardless of the tested activators, whereas the HIV-2 LTR was the most
      responsive LTR. The clade E enhancer region was also demonstrated to be the
      weakest enhancer region in transfection experiments with luciferase reporter
      based vectors. Electrophoretic mobility shift assays with extracts from activated
      CD4(+) T-cells indicated that, although NF-kappaB and NFAT bound all enhancers,
      HIV-1 clade E and HIV-2 LTR enhancers were poor binding targets for these two
      factors. Weak NFAT binding to clade E enhancers was also confirmed using NFAT1
      expressing 293T cells in competition experiments. We have also shown the absence
      of interaction of NF-kappaB or NFAT with the third NF-kappaB repeat present in
      clade C. However, the clade C enhancer bound NFAT more efficiently than all other
      enhancer regions tested. Our results hence demonstrate for the first time that
      differences in the binding of NF-kappaB and NFAT to the enhancer regions could be
      responsible for some of the observed variation in HIV-1 clade LTR activation,
      whereas HIV-2 LTR activation seems mostly independent of these interactions.

PMID- 15466413
TI  - Solution structure and dynamics of a prototypical chordin-like cysteine-rich
      repeat (von Willebrand Factor type C module) from collagen IIA.
AB  - Chordin-like cysteine-rich (CR) repeats (also referred to as von Willebrand
      factor type C (VWC) modules) have been identified in approximately 200
      extracellular matrix proteins. These repeats, named on the basis of amino acid
      conservation of 10 cysteine residues, have been shown to bind members of the
      transforming growth factor-beta (TGF-beta) superfamily and are proposed to
      regulate growth factor signaling. Here we describe the intramolecular disulfide
      bonding, solution structure, and dynamics of a prototypical chordin-like CR
      repeat from procollagen IIA (CR(ColIIA)), which has been previously shown to bind
      TGF-beta1 and bone morphogenetic protein-2. The CR(ColIIA) structure manifests a
      two sub-domain architecture tethered by a flexible linkage. Initial structures
      were calculated using RosettaNMR, a de novo prediction method, and final
      structure calculations were performed using CANDID within CYANA. The N-terminal
      region contains mainly beta-sheet and the C-terminal region is more irregular
      with the fold constrained by disulfide bonds. Mobility between the N- and C
      terminal sub-domains on a fast timescale was confirmed using NMR relaxation
      measurements. We speculate that the mobility between the two sub-domains may
      decrease upon ligand binding. Structure and sequence comparisons have revealed an
      evolutionary relationship between the N-terminal sub-domain of the CR module and
      the fibronectin type 1 domain, suggesting that these domains share a common
      ancestry. Based on the previously reported mapping of fibronectin binding sites
      for vascular endothelial growth factor to regions containing fibronectin type 1
      domains, we discuss the possibility that this structural homology might also have
      functional relevance.

PMID- 15466414
TI  - Glycogen synthase kinase 3beta is a negative regulator of growth factor-induced
      activation of the c-Jun N-terminal kinase.
AB  - The c-Jun N-terminal kinase (JNK)/stress activated protein kinase is
      preferentially activated by stress stimuli. Growth factors, particularly ligands
      for G protein-coupled receptors, usually induce only modest JNK activation,
      although they may trigger marked activation of the related extracellular signal
      regulated kinase. In the present study, we demonstrated that homozygous
      disruption of glycogen synthase kinase 3beta (GSK-3beta) dramatically sensitized
      mouse embryonic fibroblasts (MEFs) to JNK activation induced by lysophosphatidic
      acid (LPA) and sphingosine-1-phosphate, two prototype ligands for G protein
      coupled receptors. To a lesser degree, a lack of GSK-3beta also potentiated JNK
      activation in response to epidermal growth factor. In contrast, the absence of
      GSK-3beta decreased UV light-induced JNK activation. The increased JNK activation
      induced by LPA in GSK-3beta null MEFs was insufficient to trigger apoptotic cell
      death or growth inhibition. Instead, the increased JNK activation observed in GSK
      3beta-/- MEFs was associated with an increased proliferative response to LPA,
      which was reduced by the inhibition of JNK. Ectopic expression of GSK-3beta in
      GSK-3beta-negative MEFs restrained LPA-triggered JNK phosphorylation and induced
      a concomitant decrease in the mitogenic response to LPA compatible with GSK-3beta
      through the inhibition of JNK activation, thus limiting LPA-induced cell
      proliferation. Mutation analysis indicated that GSK-3beta kinase activity was
      required for GSK-3beta to optimally inhibit LPA-stimulated JNK activation. Thus
      GSK-3beta serves as a physiological switch to specifically repress JNK activation
      in response to LPA, sphingosine-1-phosphate, or the epidermal growth factor.
      These results reveal a novel role for GSK-3beta in signal transduction and
      cellular responses to growth factors.

PMID- 15466415
TI  - Negative feedback exerted by cAMP-dependent protein kinase and cAMP
      phosphodiesterase on subsarcolemmal cAMP signals in intact cardiac myocytes: an
      in vivo study using adenovirus-mediated expression of CNG channels.
AB  - Intracardiac cAMP levels are modulated by hormones and neuromediators with
      specific effects on contractility and metabolism. To understand how the same
      second messenger conveys different information, mutants of the rat olfactory
      cyclic nucleotide-gated (CNG) channel alpha-subunit CNGA2, encoded into
      adenoviruses, were used to monitor cAMP in adult rat ventricular myocytes. CNGA2
      was not found in native myocytes but was strongly expressed in infected cells. In
      whole cell patch-clamp experiments, the forskolin analogue L-858051 (L-85)
      elicited a non-selective, Mg2+ -sensitive current observed only in infected
      cells, which was thus identified as the CNG current (ICNG). The beta-adrenergic
      agonist isoprenaline (ISO) also activated ICNG, although the maximal efficiency
      was approximately 5 times lower than with L-85. However, ISO and L-85 exerted a
      similar maximal increase of the L-type Ca2+ current. The use of a CNGA2 mutant
      with a higher sensitivity for cAMP indicated that this difference is caused by
      the activation of a localized fraction of CNG channels by ISO. cAMP-dependent
      protein kinase (PKA) blockade with H89 or PKI, or phosphodiesterase (PDE)
      inhibition with IBMX, dramatically potentiated ISO- and L-85-stimulated ICNG. A
      similar potentiation of beta-adrenergic stimulation occurred when PDE4 was
      blocked, whereas PDE3 inhibition had a smaller effect (by 2-fold). ISO and L-85
      increased total PDE3 and PDE4 activities in cardiomyocytes, although this effect
      was insensitive to H89. However, in the presence of IBMX, H89 had no effect on
      ISO stimulation of ICNG. This study demonstrates that subsarcolemmal cAMP levels
      are dynamically regulated by a negative feedback involving PKA stimulation of
      subsarcolemmal cAMP-PDE.

PMID- 15466416
TI  - Cell-specific activation of the atrial natriuretic factor promoter by PITX2 and
      MEF2A.
AB  - The PITX2 homeodomain protein is mutated in patients with Axenfeld-Rieger
      syndrome and is involved in the development of multiple organ systems, including
      the heart. We have examined the interaction of PITX2 isoforms with myocyte
      enhancing factor 2A (MEF2A), which is a known regulator of cardiac development. A
      direct interaction between PITX2a and MEF2A was demonstrated using yeast two
      hybrid and GST pull-down assays. To study the functional significance of this
      interaction, we used the atrial natriuretic factor (ANF) promoter. Coexpression
      of MEF2A and PITX2a or Pitx2c resulted in a strong synergistic activation of the
      ANF promoter in LS8 oral epithelial cells but not in other cell lines (NIH/3T3,
      Chinese hamster ovary, or C2C12). The synergism was dependent on promoter
      context, because it required MEF2 binding sites and was not seen with two other
      PITX2 target promoters. DNA binding by MEF2A was required but not sufficient for
      synergism. Upstream activators of p38 MAP kinases, MKK3 and MKK6, increased
      PITX2a and Pitx2c activity to yield up to 90-fold activation of the ANF promoter
      in LS8 cells. Because Axenfeld-Rieger syndrome is autosomal dominant and affects
      development of the oral epithelium, we tested one of the known PITX2 mutants. The
      PITX2a-K88E mutant protein suppressed wild type PITX2a synergism with MEF2A.
      These results demonstrate a promoter- and cell-specific functional interaction
      between PITX2 and MEF2A and suggest the possibility of coordinate control by
      these factors in the oral epithelium.

PMID- 15466417
TI  - Regulation of leucine uptake by tor1+ in Schizosaccharomyces pombe is sensitive
      to rapamycin.
AB  - TOR protein kinases are key regulators of cell growth in eukaryotes. TOR is also
      known as the target protein for the immunosuppressive and potentially anticancer
      drug rapamycin. The fission yeast Schizosaccharomyces pombe has two TOR homologs.
      tor1+ is required under starvation and a variety of stresses, while tor2+ is an
      essential gene. Surprisingly, to date no rapamycin-sensitive TOR-dependent
      function has been identified in S. pombe. Herein, we show that S. pombe
      auxotrophs, in particular leucine auxotrophs, are sensitive to rapamycin. This
      sensitivity is suppressed by deletion of the S. pombe FKBP12 or by introducing a
      rapamycin-binding defective tor1 allele, suggesting that rapamycin inhibits a
      tor1p-dependent function. Sensitivity of leucine auxotrophs to rapamycin is
      observed when ammonia is used as the nitrogen source and can be suppressed by its
      replacement with proline. Consistently, using radioactive labeled leucine, we
      show that cells treated with rapamycin or disrupted for tor1+ are defective in
      leucine uptake when the nitrogen source is ammonia but not proline. Recently, it
      has been reported that tsc1+ and tsc2+, the S. pombe homologs for the mammalian
      TSC1 and TSC2, are also defective in leucine uptake. TSC1 and TSC2 may antagonize
      TOR signaling in mammalian cells and Drosophila. We show that reduction of
      leucine uptake in tor1 mutants is correlated with decreased expression of three
      putative amino acid permeases that are also downregulated in tsc1 or tsc2. These
      findings suggest a possible mechanism for regulation of leucine uptake by tor1p
      and indicate that tor1p, as well as tsc1p and tsc2p, positively regulates leucine
      uptake in S. pombe.

PMID- 15466418
TI  - On the evolution of codon volatility.
AB  - Volatility of a codon is defined as the probability that a random point mutation
      in the codon generates a nonsynonymous change. It has been proposed that higher
      than-expected mean codon volatility of a gene indicates that positive selection
      for nonsynonymous changes has acted on the gene in the recent past. I show that
      strong frequency-dependent selection (minority advantage) in large populations
      can increase codon volatility slightly, whereas directional positive selection
      has no effect on volatility. Factors unrelated to positive selection, such as
      expression-related or GC-content-related codon usage bias, also affect
      volatility. These and other considerations suggest that codon volatility has only
      limited utility for detecting positive selection at the DNA sequence level.

PMID- 15466419
TI  - Swi5 acts in meiotic DNA joint molecule formation in Schizosaccharomyces pombe.
AB  - Previously isolated Schizosaccharomyces pombe swi5 mutants are defective in
      mitotic mating-type switching and in repair of meiotic recombination-related DNA
      double-strand breaks. Here, we identify the swi5 gene, which encodes an 85-amino
      acid polypeptide, similar to Sae3 of Saccharomyces cerevisiae, with an N-terminal
      predicted coiled-coil domain. A swi5 complete deletion mutant had normal mitotic
      growth rate but was hypersensitive to DNA-damaging agents and defective in mating
      type switching. In meiosis, recombinant frequencies were reduced by a factor of
      approximately 10. The swi5 deletion strongly reduced the viable spore yields of
      mutants lacking Rhp55 or Rhp57, proteins thought to aid joint molecule formation.
      Furthermore, the swi5 deletion strongly suppressed the low viable spore yield of
      mutants lacking Mus81*Eme1, which resolves joint molecules such as Holliday
      junctions. These and previous results indicate that the small Swi5 polypeptide
      acts in a branched pathway of joint molecule formation to repair meiotic DNA
      breaks.

PMID- 15466420
TI  - Satellite DNA from the Y chromosome of the malaria vector Anopheles gambiae.
AB  - Satellite DNA is an enigmatic component of genomic DNA with unclear function that
      has been regarded as "junk." Yet, persistence of these tandem highly repetitive
      sequences in heterochromatic regions of most eukaryotic chromosomes attests to
      their importance in the genome. We explored the Anopheles gambiae genome for the
      presence of satellite repeats and identified 12 novel satellite DNA families.
      Certain families were found in close juxtaposition within the genome. Six
      satellites, falling into two evolutionarily linked groups, were investigated in
      detail. Four of them were experimentally confirmed to be linked to the Y
      chromosome, whereas their relatives occupy centromeric regions of either the X
      chromosome or the autosomes. A complex evolutionary pattern was revealed among
      the AgY477-like satellites, suggesting their rapid turnover in the A. gambiae
      complex and, potentially, recombination between sex chromosomes. The substitution
      pattern suggested rolling circle replication as an array expansion mechanism in
      the Y-linked 53-bp satellite families. Despite residing in different portions of
      the genome, the 53-bp satellites share the same monomer lengths, apparently
      maintained by molecular drive or structural constraints. Potential functional
      centromeric DNA structures, consisting of twofold dyad symmetries flanked by a
      common sequence motif, have been identified in both satellite groups.

PMID- 15466421
TI  - A screen for Schizosaccharomyces pombe mutants defective in rereplication
      identifies new alleles of rad4+, cut9+ and psf2+.
AB  - Fission yeast mutants defective in DNA replication have widely varying
      morphological phenotypes. We designed a screen for temperature-sensitive mutants
      defective in the process of replication regardless of morphology by isolating
      strains unable to rereplicate their DNA in the absence of cyclin B (Cdc13). Of
      the 42 rereplication-defective mutants analyzed, we were able to clone
      complementing plasmids for 10. This screen identified new alleles of the APC
      subunit cut9(+), the initiation/checkpoint factor rad4(+)/cut5(+), and the first
      mutant allele of psf2(+), a subunit of the novel GINS replication complex. Other
      genes identified are likely to play general roles in gene expression and protein
      localization.

PMID- 15466422
TI  - Mapping a syntenic modifier on mouse chromosome 1 influencing the expressivity of
      the compact phenotype in the myostatin mutant (MstnCmpt-dl1Abc) compact mouse.
AB  - A novel method for mapping a modifier gene that is syntenic to its major gene was
      used to map a male-sex-limited modifier of the expressivity of the Compact
      phenotype in the myostatin mutant (Mstn(Cmpt-dl1Abc)) Compact mouse. The modifier
      was mapped to the general region of D1Mit262, 40 cM distal to Mstn on chromosome
      1. Myogenin, a postulated downstream target of myostatin, maps to the same
      region.

PMID- 15466423
TI  - Genetic evidence for a regulatory pathway controlling alternative oxidase
      production in Neurospora crassa.
AB  - When the cytochrome-mediated mitochondrial electron transport chain of Neurospora
      crassa is disrupted, an alternative oxidase encoded by the nuclear aod-1 gene is
      induced. The alternative oxidase donates electrons directly to oxygen from the
      ubiquininol pool and is insensitive to chemicals such as antimycin A and KCN that
      affect the standard electron transport chain. To facilitate isolation of mutants
      affecting regulation of aod-1, a reporter system containing the region upstream
      of the aod-1 coding sequence fused to the coding sequence of the N. crassa
      tyrosinase gene (T) was transformed into a strain carrying a null allele of the
      endogenous T gene. In the resulting reporter strain, growth in the presence of
      chloramphenicol, an inhibitor of mitochondrial translation whose action decreases
      the level of mitochondrial translation products resulting in impaired cytochrome
      mediated respiration, caused induction of both alternative oxidase and
      tyrosinase. Conidia from the reporter strain were mutagenized, plated on medium
      containing chloramphenicol, and colonies that did not express tyrosinase were
      identified as potential regulatory mutants. After further characterization, 15
      strains were found that were unable to induce both the reporter and the
      alternative oxidase. Complementation analysis revealed that four novel loci
      involved in aod-1 regulation had been isolated. The discovery that several genes
      are required for regulation of aod-1 suggests the existence of a complex pathway
      for signaling from the mitochondria to the nucleus and/or for expression of the
      gene.

PMID- 15466424
TI  - Mss11p is a central element of the regulatory network that controls FLO11
      expression and invasive growth in Saccharomyces cerevisiae.
AB  - The invasive and filamentous growth forms of Saccharomyces cerevisiae are
      adaptations to specific environmental conditions, under particular conditions of
      limited nutrient availability. Both growth forms are dependent on the expression
      of the FLO11 gene, which encodes a cell-wall-associated glycoprotein involved in
      cellular adhesion. A complex regulatory network consisting of signaling pathways
      and transcription factors has been associated with the regulation of FLO11.
      Mss11p has been identified as a transcriptional activator of this gene, and here
      we present an extensive genetic analysis to identify functional relationships
      between Mss11p and other FLO11 regulators. The data show that Mss11p is
      absolutely required for the activation of FLO11 by most proteins that have
      previously been shown to affect FLO11 expression, including the signaling
      proteins Ras2p, Kss1p, and Tpk2p, the activators Tec1p, Flo8p, and Phd1p, and the
      repressors Nrg1p, Nrg2p, Sok2p, and Sfl1p. The genetic evidence furthermore
      suggests that Mss11p activity is not dependent on the presence of any of the
      above-mentioned factors and that the protein also regulates other genes involved
      in cellular adhesion phenotypes. Taken together, the data strongly suggest a
      central role for Mss11p in the regulatory network controlling FLO11 expression,
      invasive growth, and pseudohyphal differentiation.

PMID- 15466425
TI  - Sperm competitive ability in Drosophila melanogaster associated with variation in
      male reproductive proteins.
AB  - Multiple mating by females establishes the opportunity for postcopulatory sexual
      selection favoring males whose sperm is preferentially employed in
      fertilizations. Here we use natural variation in a wild population of Drosophila
      melanogaster to investigate the genetic basis of sperm competitive ability.
      Approximately 101 chromosome 2 substitution lines were scored for components of
      sperm competitive ability (P1', P2', fecundity, remating rate, and
      refractoriness), genotyped at 70 polymorphic markers in 10 male reproductive
      genes, and measured for transcript abundance of those genes. Permutation tests
      were applied to quantify the statistical significance of associations between
      genotype and phenotype. Nine significant associations were identified between
      polymorphisms in the male reproductive genes and sperm competitive ability and 13
      were identified between genotype and transcript abundance, but no significant
      associations were found between transcript abundance and sperm competitive
      ability. Pleiotropy was evident in two genes: a polymorphism in Acp33A associated
      with both P1' and P2' and a polymorphism in CG17331 associated with both elevated
      P2' and reduced refractoriness. The latter case is consistent with antagonistic
      pleiotropy and may serve as a mechanism maintaining genetic variation.

PMID- 15466426
TI  - A novel meiotic drive locus almost completely distorts segregation in mimulus
      (monkeyflower) hybrids.
AB  - We report the discovery, mapping, and characterization of a meiotic drive locus
      (D) exhibiting nearly 100% nonrandom transmission in hybrids between two species
      of yellow monkeyflowers, outcrossing Mimulus guttatus and selfing M. nasutus.
      Only 1% of F(2) hybrids were M. nasutus homozygotes at the marker most tightly
      linked to D. We used a set of reciprocal backcrosses to distinguish among male
      specific, female-specific, and zygote-specific sources of transmission ratio
      distortion. Transmission was severely distorted only when the heterozygous F(1)
      acted as the female parent in crosses to either parental species, ruling out
      pollen competition and zygote mortality as potential sources of drive. After four
      generations of backcrossing to M. nasutus, nearly isogenic lines were still >90%
      heterozygous at markers linked to D, suggesting that heterozygosity at the drive
      locus alone is sufficient for nonrandom transmission. A lack of dramatic female
      fitness costs in these lines rules out alternatives involving ovule or seed
      mortality and points to a truly meiotic mechanism of drive. The strength and
      direction of drive in this system is consistent with population genetic theory of
      selfish element evolution under different mating systems. These results are the
      first empirical demonstration of the strong female-specific drive predicted by
      new models of selfish centromere turnover.

PMID- 15466427
TI  - High-resolution mapping of the Drosophila fourth chromosome using site-directed
      terminal deficiencies.
AB  - For more than 80 years, the euchromatic right arm of the Drosophila fourth
      chromosome (101F-102F) has been one of the least genetically accessible regions
      of the fly genome despite the fact that many important genes reside there. To
      improve the mapping of genes on the fourth chromosome, we describe a strategy to
      generate targeted deficiencies and we describe 13 deficiencies that subdivide the
      300 kb between the cytological coordinates 102A6 and 102C1 into five discrete
      regions plus a 200-kb region from 102C1 to 102D6. Together these deficiencies
      substantially improve the mapping capabilities for mutant loci on the fourth
      chromosome.

PMID- 15466428
TI  - Communication between parental and developing genomes during tetrahymena nuclear
      differentiation is likely mediated by homologous RNAs.
AB  - Approximately 6000 DNA elements, totaling nearly 15 Mb, are coordinately excised
      from the developing somatic genome of Tetrahymena thermophila. An RNA
      interference (RNAi)-related mechanism has been implicated in the targeting of
      these germline-limited sequences for chromatin modification and subsequent DNA
      rearrangement. The excision of individual DNA segments can be inhibited if the
      homologous sequence is placed within the parental somatic nucleus, indicating
      that communication occurs between the parental and developing genomes. To
      determine how the DNA content of one nucleus is communicated to the other, we
      assessed DNA rearrangement occurring in wild-type cells that were mated to cells
      that contained the normally germline-limited M element within their somatic
      nuclei. M-element rearrangement was blocked in the wild-type cell even when no
      genetic exchange occurred between mating partners, a finding that is inconsistent
      with any genetic imprinting models. This inhibition by the parental somatic
      nucleus was rapidly established between 5 and 6 hr of conjugation, near or
      shortly after the time that zygotic nuclei are formed. M-element small RNAs
      (sRNAs) that are believed to direct its rearrangement were found to rapidly
      accumulate during the first few hours of conjugation before stabilizing to a low,
      steady-state level. The period between 5 and 6 hr during which sRNA levels
      stabilize correlates with the time after which the parental genome can block DNA
      rearrangement. These data lead us to suggest that homologous sRNAs serve as
      mediators to communicate sequence-specific information between the parental and
      developing genomes, thereby regulating genome-wide DNA rearrangement, and that
      these sRNAs can be effectively compared to the somatic genome of both parents.

PMID- 15466429
TI  - The influence of genes on the aging process of mice: a statistical assessment of
      the genetics of aging.
AB  - Genetic interventions that accelerate or retard aging in mice are crucial in
      advancing our knowledge over mammalian aging. Yet determining if a given
      intervention affects the aging process is not straightforward since, for
      instance, many disease-causing mutations may decrease life span without affecting
      aging. In this work, we employed the Gompertz model to determine whether several
      published interventions previously claimed to affect aging in mice do indeed
      alter the aging process. First, we constructed age-specific mortality tables for
      a number of mouse cohorts used in longevity experiments and calculated the rate
      at which mortality increases with age. Estimates of age-independent mortality
      were also calculated. We found no statistical evidence that GHRHR, IGF1R, INSR,
      PROP1, or TRX delay or that ATM + TERC, BubR1, klotho, LMNA, PRDX1, p53, WRN +
      TERC, or TOP3B accelerate mouse aging. Often, changes in the expression of these
      genes affected age-independent mortality and so they may prove useful to other
      aspects of medicine. We found statistical evidence that C/EBP, MSRA, SHC1, growth
      hormone, GHR, PIT1, and PolgA may influence aging in mice. These results were
      interpreted together with age-related physiological and pathological changes and
      provide novel insights regarding the role of several genes in the mammalian aging
      process.

PMID- 15466430
TI  - The dynamics of transposable elements in structured populations.
AB  - We analyzed the dynamics of transposable elements (TEs) according to Wright's
      island and continent-island models, assuming that selection tends to counter the
      deleterious effects of TEs. We showed that migration between host populations has
      no impact on either the existence or the stability of the TE copy number
      equilibrium points obtained in the absence of migration. However, if the
      migration rate is slower than the transposition rate or if selection is weak,
      then the TE copy numbers in all the populations can be expected to slowly become
      homogeneous, whereas a heterogeneous TE copy number distribution between
      populations is maintained if TEs are mobilized in some populations. The mean TE
      copy number is highly sensitive to the population size, but as a result of
      migration between populations, it decreases as the sum of the population sizes
      increases and tends to reach the same value in these populations. We have
      demonstrated the existence of repulsion between TE insertion sites, which is
      established by selection and amplified by drift. This repulsion is reduced as
      much as the migration rate is higher than the recombination rate between the TE
      insertion sites. Migration and demographic history are therefore strong forces in
      determining the dynamics of TEs within the genomes and the populations of a
      species.

PMID- 15466431
TI  - Epistasis underlying a fitness trait within a natural population of the pitcher
      plant mosquito, Wyeomyia smithii.
AB  - We selected on divergent photoperiodic response in three separate lines from a
      natural population of the pitcher-plant mosquito, Wyeomyia smithii. Line crosses
      reveal that there exists within a population, diverse epistatic variation for a
      fitness trait that could contribute to adaptive potential following founder
      events or rapid climate change.

PMID- 15466432
TI  - The Bacillus subtilis sin operon: an evolvable network motif.
AB  - The strategy of combining genes from a regulatory protein and its antagonist
      within the same operon, but controlling their activities differentially, can lead
      to diverse regulatory functions. This protein-antagonist motif is ubiquitous and
      present in evolutionarily unrelated regulatory pathways. Using the sin operon
      from the Bacillus subtilis sporulation pathway as a model system, we built a
      theoretical model, parameterized it using data from the literature, and used
      bifurcation analyses to determine the circuit functions it could encode. The
      model demonstrated that this motif can generate a bistable switch with tunable
      control over the switching threshold and the degree of population heterogeneity.
      Further, the model predicted that a small perturbation of a single critical
      parameter can bias this architecture into functioning like a graded response, a
      bistable switch, an oscillator, or a pulse generator. By mapping the parameters
      of the model to specific DNA regions and comparing the genomic sequences of
      Bacillus species, we showed that phylogenetic variation tends to occur in those
      regions that tune the switch threshold without disturbing the circuit function.
      The dynamical plasticity of the protein-antagonist operon motif suggests that it
      is an evolutionarily convergent design selected not only for particular immediate
      function but also for its evolvability.

PMID- 15466433
TI  - Mapping of a milk production quantitative trait locus to a 420-kb region on
      bovine chromosome 6.
AB  - A QTL affecting milk production traits was previously mapped to an interval of
      7.5 cM on chromosome 6 in Norwegian dairy cattle. This article aimed to refine
      this position by increasing the map density in the region by a set of single
      nucleotide polymorphisms and analyzing the data with a combined linkage and
      linkage disequilibrium approach. Through a series of single- and multitrait and
      single- and multipoint analyses, the QTL was positioned to an interval surrounded
      by the genes ABCG2 and LAP3. As no recombinations were detected in this interval,
      physical mapping was required for further refining. By using radiation hybrid
      mapping as well as BAC clones, the bovine and human comparative maps in the
      region are resolved, and the QTL is mapped within a distance of 420 kb.

PMID- 15466434
TI  - Ccr4-not complex mRNA deadenylase activity contributes to DNA damage responses in
      Saccharomyces cerevisiae.
AB  - DNA damage checkpoints regulate gene expression at the transcriptional and post
      transcriptional level. Some components of the yeast Ccr4-Not complex, which
      regulates transcription as well as transcript turnover, have previously been
      linked to DNA damage responses, but it is unclear if this involves
      transcriptional or post-transcriptional functions. Here we show that CCR4 and
      CAF1, which together encode the major cytoplasmic mRNA deadenylase complex, have
      complex genetic interactions with the checkpoint genes DUN1, MRC1, RAD9, and
      RAD17 in response to DNA-damaging agents hydroxyurea (HU) and methylmethane
      sulfonate (MMS). The exonuclease-inactivating ccr4-1 point mutation mimics
      ccr4Delta phenotypes, including synthetic HU hypersensitivity with dun1Delta,
      demonstrating that Ccr4-Not mRNA deadenylase activity is required for DNA damage
      responses. However, ccr4Delta and caf1Delta DNA damage phenotypes and genetic
      interactions with checkpoint genes are not identical, and deletions of some Not
      components that are believed to predominantly function at the transcriptional
      level rather than mRNA turnover, e.g., not5Delta, also lead to increased DNA
      damage sensitivity and synthetic HU hypersensitivity with dun1Delta. Taken
      together, our data thus suggest that both transcriptional and post
      transcriptional functions of the Ccr4-Not complex contribute to the DNA damage
      response affecting gene expression in a complex manner.

PMID- 15466435
TI  - Longevity and metabolism in Drosophila melanogaster: genetic correlations between
      life span and age-specific metabolic rate in populations artificially selected
      for long life.
AB  - We measured age-specific metabolic rates in 2861 individual Drosophila
      melanogaster adult males to determine how genetic variation in metabolism is
      related to life span. Using recombinant inbred (RI) lines derived from
      populations artificially selected for long life, resting metabolic rates were
      measured at 5, 16, 29, and 47 days posteclosion, while life spans were measured
      in the same genotypes in mixed-sex population cages and in single-sex vials. We
      observed much heritable variation between lines in age-specific metabolic rates,
      evidence for genotype x age interaction, and moderate to large heritabilities at
      all ages except the youngest. Four traits exhibit evidence of coordinate genetic
      control: day 16 and day 29 metabolic rates, life span in population cages, and
      life span in vials. Quantitative trait loci (QTL) for those traits map to the
      same locations on three major chromosomes, and additive genetic effects are all
      positively correlated. In contrast, metabolic rates at the youngest and oldest
      ages are unrelated to metabolic rates at other ages and to survival. We suggest
      that artificial selection for long life via delayed reproduction also selects for
      increased metabolism at intermediate ages. Contrary to predictions of the "rate
      of living" theory, we find no evidence that metabolic rate varies inversely with
      survival, at the level of either line means or additive effects of QTL.

PMID- 15466436
TI  - Genetics of hybrid incompatibility between Lycopersicon esculentum and L.
      hirsutum.
AB  - We examined the genetics of hybrid incompatibility between two closely related
      diploid hermaphroditic plant species. Using a set of near-isogenic lines (NILs)
      representing 85% of the genome of the wild species Lycopersicon hirsutum (Solanum
      habrochaites) in the genetic background of the cultivated tomato L. esculentum
      (S. lycopersicum), we found that hybrid pollen and seed infertility are each
      based on 5-11 QTL that individually reduce hybrid fitness by 36-90%. Seed
      infertility QTL act additively or recessively, consistent with findings in other
      systems where incompatibility loci have largely been recessive. Genetic lengths
      of introgressed chromosomal segments explain little of the variation for hybrid
      incompatibility among NILs, arguing against an infinitesimal model of hybrid
      incompatibility and reinforcing our inference of a limited number of discrete
      incompatibility factors between these species. In addition, male (pollen) and
      other (seed) incompatibility factors are roughly comparable in number. The latter
      two findings contrast strongly with data from Drosophila where hybrid
      incompatibility can be highly polygenic and complex, and male sterility evolves
      substantially faster than female sterility or hybrid inviability. The observed
      differences between Lycopersicon and Drosophila might be due to differences in
      sex determination system, reproductive and mating biology, and/or the prevalence
      of sexual interactions such as sexual selection.

PMID- 15466437
TI  - Using molecular sizes of simple sequence repeats vs. discrete binned data in
      assessing probability of ancestry: application to maize hybrids.
AB  - Most inferential methods for profiling genotypes based upon the use of DNA
      fragments use molecular-size data transcribed into discrete bins, which are
      intervals of DNA fragment sizes. Categorizing into bins is labor intensive with
      inevitable arbitrariness that may vary between laboratories. We describe and
      evaluate an algorithm for determining probabilities of parentage based on raw
      molecular-size data without establishing bins. We determine the standard
      deviation of DNA fragment size and assess the association of standard deviation
      with fragment size. We consider a pool of potential ancestors for an index line
      that is a hybrid with unknown pedigree. We evaluate the identification of inbred
      parents of maize hybrids with simple sequence repeat data in the form of actual
      molecular sizes received from two laboratories. We find the standard deviation to
      be essentially constant over the molecular weight. We compare these results with
      those of parallel analyses based on these same data that had been transcribed
      into discrete bins by the respective laboratories. The conclusions were quite
      similar in the two cases, with excellent performance using either binned or
      molecular-size data. We demonstrate the algorithm's utility and robustness
      through simulations of levels of missing and misscored molecular-size data.

PMID- 15466438
TI  - Co-chaperone regulation of conformational switching in the Hsp90 ATPase cycle.
AB  - ATP hydrolysis by the Hsp90 molecular chaperone requires a connected set of
      conformational switches triggered by ATP binding to the N-terminal domain in the
      Hsp90 dimer. Central to this is a segment of the structure, which closes like a
      "lid" over bound ATP, promoting N-terminal dimerization and assembly of a
      competent active site. Hsp90 mutants that influence these conformational switches
      have strong effects on ATPase activity. ATPase activity is specifically regulated
      by Hsp90 co-chaperones, which directly influence the conformational switches.
      Here we have analyzed the effect of Hsp90 mutations on binding (using isothermal
      titration calorimetry and difference circular dichroism) and ATPase regulation by
      the co-chaperones Aha1, Sti1 (Hop), and Sba1 (p23). The ability of Sti1 to bind
      Hsp90 and arrest its ATPase activity was not affected by any of the mutants
      screened. Sba1 bound in the presence of AMPPNP to wild-type and ATPase
      hyperactive mutants with similar affinity but only very weakly to hypoactive
      mutants despite their wild-type ATP affinity. Unexpectedly, in all cases Sba1
      bound to Hsp90 with a 1:2 molar stoichiometry. Aha1 binding to mutants was
      similar to wild-type, but the -fold activation of their ATPase varied
      substantially between mutants. Analysis of complex formation with co-chaperone
      mixtures showed Aha1 and p50cdc37 able to bind Hsp90 simultaneously but without
      direct interaction. Sba1 and p50cdc37 bound independently to Hsp90-AMPPNP but not
      together. These data indicated that Sba1 and Aha1 regulate Hsp90 by influencing
      the conformational state of the "ATP lid" and consequent N-terminal dimerization,
      whereas Sti1 does not.

PMID- 15466439
TI  - Hexameric assembly of the bifunctional methylerythritol 2,4-cyclodiphosphate
      synthase and protein-protein associations in the deoxy-xylulose-dependent pathway
      of isoprenoid precursor biosynthesis.
AB  - The bifunctional methylerythritol 4-phosphate cytidylyltransferase
      methylerythritol 2,4-cyclodiphosphate synthase (IspDF) is unusual in that it
      catalyzes nonconsecutive reactions in the 1-deoxy-D-xylulose 5-phosphate (DOXP)
      pathway of isoprenoid precursor biosynthesis. The crystal structure of IspDF from
      the bacterial pathogen Campylobacter jejuni reveals an elongated hexamer with D3
      symmetry compatible with the dimeric 2C-methyl-D-erythritol-4-phosphate
      cytidylyltransferase and trimeric 2C-methyl-D-erythritol-2,4-cyclodiphosphate
      synthase monofunctional enzymes. Complex formation of IspDF with 4
      diphosphocytidyl-2C-methyl-D-erythritol kinase (IspE), the intervening enzyme
      activity in the pathway, has been observed in solution for the enzymes from C.
      jejuni and Agrobacterium tumefaciens. The monofunctional enzymes (2C-methyl-D
      erythritol-4-phosphate cytidylyltransferase, IspE, and 2C-methyl-D-erythritol-2,4
      cyclodiphosphate synthase) involved in the DOXP biosynthetic pathway of
      Escherichia coli also show physical associations. We propose that complex
      formation of the three enzymes at the core of the DOXP pathway can produce an
      assembly localizing 18 catalytic centers for the early stages of isoprenoid
      biosynthesis.

PMID- 15466440
TI  - Novel role for P2X receptor activation in endothelium-dependent vasodilation.
AB  - 1 ATP is an important vasoactive mediator, which acts via two receptor classes:
      P2X and P2Y. Activation of P2X receptors has traditionally been associated with
      the well-characterised vasoconstrictor properties of ATP. 2 In the current study,
      we have shown that the P2X(1 & 3) receptor ligand, alpha, beta methylene ATP,
      induces vasodilation of rat isolated mesenteric arteries and that P2X1 receptors
      are abundantly expressed in the endothelium of these vessels. 3 Second-order rat
      mesenteric arteries were mounted in myographs and vasomotor responses recorded.
      Both ATP and alpha, beta methylene ATP induced a constriction followed by a
      vasodilation. The dilator effects of either ATP or alpha, beta methylene ATP were
      slower in onset than those induced by acetylcholine. By contrast, the traditional
      vasodilator P2Y ligand, ADP, induced vasodilation without contraction. 4
      Vasodilation induced by alpha, beta methylene ATP was endothelial dependent, but
      was not affected by treatment of the vessels with L-NAME plus indomethacin alone.
      Dilation was, however, partially inhibited by the combination of apamin plus
      charybdotoxin and blocked by treating vessels with all four drugs. 5 Using
      confocal microscopy, P2X1 receptor immunoreactivity was localised to the
      endothelial, smooth muscle and adventitial layers of mesenteric vessels. P2X1
      protein migrated as a primary band at around 50-60 kDa in vascular tissue. 6
      These results show for the first time that P2X1 receptors are expressed on the
      endothelium and that a selective ligand of this receptor results in
      vasoconstriction followed by vasodilation. These observations have important
      implications for our understanding of the role of purines in biological
      responses.

PMID- 15466441
TI  - Glucocorticoid hormone (cortisol) affects axonal transport in human cortex
      neurons but shows resistance in Alzheimer's disease.
AB  - 1 The changes of tissue sensitivity to glucocorticoids are associated with many
      pathological states including neurological diseases. In the present study, using
      a novel in vitro post-mortem tracing method on human brain slices, we
      demonstrated that cortisol, a major glucocorticoid hormone in humans, affected
      axonal transport both in the cortex neurons in four Alzheimer's disease (AD)
      patients and four nondemented controls. 2 Cortisol appeared to affect axonal
      transport of prefrontal cortex (PFC) and temporal cortex (TC) neurons in AD
      patients and controls in a dose-dependent way at concentrations of 30, 60, 120
      and 240 microg dl(-1). 3 Higher doses of cortisol were needed for TC neurons to
      achieve a similar axonal transport effect as obtained in PFC neurons in AD
      patients. The maximum effect (Emax) on axonal transport was achieved in PFC
      slices at relatively low contraction (30-120 microg dl(-1)), while in TC slices,
      a maximum effect was only reached at relatively high concentrations (120-240
      microg dl(-1)). 4 For PFC and TC slices from nondemented aging subjects, lower
      doses of cortisol (30-60 microg dl(-1)) on axonal transport were sufficient to
      achieve the maximum effect as compared to those used in AD brain slices, while
      levels of more than 60 microg dl(-1) of cortisol mostly depressed axonal
      transport. 5 These results suggest that glucocorticoid resistance, which is
      thought to contribute to the pathogenesis of a number of common human disorders,
      may exist in AD brains and play an important role in neuropathological mechanisms
      and dementia.

PMID- 15466442
TI  - Tedisamil attenuates foetal transformation of myosin in the hypertrophied rat
      myocardium.
AB  - 1 Reduction in repolarizing potassium currents has controversial effects on
      hypertrophic responses in cardiomyocytes of transgenic models and cultured
      cardiomyocytes. It remains thus unknown whether a blockade of potassium channels
      with tedisamil (N,N'dicyclopropylmethylene-9,9-tetramethylene-3,7
      diazabicyclo(3.3.1)nonane dihydrochloride) has any effects on cardiac growth
      during postnatal development or pressure overload. 2 To test the hypothesis that
      a treatment with tedisamil affects cardiac growth or protein phenotype, sham
      operated rats and rats with ascending aorta constriction were treated with
      tedisamil (36 mg kg day(-1)) for 7 weeks. Left ventricular mass and geometry,
      relative expression of myosin isoforms, hydroxyproline concentration and
      isovolumic ventricular function were assessed. 3 Rats with aortic constriction
      exhibited a marked increase in left ventricular weight and the diastolic pressure
      volume relationship was shifted to smaller volumes. The hydroxyproline
      concentration remained unaltered. The proportion of alpha-myosin heavy chains
      was, however, reduced (P<0.05). Hypertrophied left ventricles manifested an
      enhanced overall performance but depressed myocardial contractility. 4
      Administration of tedisamil was associated with decreased heart rate (P<0.05). In
      contrast, cardiac growth in sham-operated rats and concentric left ventricular
      hypertrophy of pressure-overloaded animals was not significantly altered.
      Hypertrophied hearts from rats treated with tedisamil expressed more alpha-myosin
      heavy chains (65+/-4 versus 57+/-4%; P<0.05). Also, maximal rate of wall stress
      rise and decline was higher (P<0.05) in tedisamil-treated pressure-overloaded
      rats. 5 In the rat model of pressure-overloaded hypertrophy, tedisamil had no
      effect on cardiac growth but partially corrected myocardial dysfunction.
      Postulated mechanism of this effect is the phenotype modification of myosin
      filaments in hypertrophied myocardium.

PMID- 15466443
TI  - Impairment of the low-affinity state beta1-adrenoceptor-induced relaxation in
      spontaneously hypertensive rats.
AB  - 1 In hypertension, a decrease of the vascular beta-adrenergic relaxation has been
      described. However, the specific involvement of each beta-adrenoceptor (beta-AR)
      subtype, in particular the low-affinity state of beta1-AR, has not yet been
      evaluated. We investigated whether the low-affinity state of beta1-AR-induced
      relaxation was impaired in Spontaneously Hypertensive Rats (SHR). 2 The relaxant
      responses to CGP 12177 and cyanopindolol, low-affinity state beta1-AR agonists
      (with beta1-/beta2-AR antagonistic and partial beta3-AR agonistic properties)
      were evaluated on thoracic aortic rings isolated from 12-weeks-old Wistar Kyoto
      rats (WKY) and SHR. 3 In WKY, CGP 12177 and cyanopindolol produced an endothelium
      and nitric oxide (NO)-independent relaxation. CGP 12177-induced endothelium
      independent relaxation was not modified either by beta1-, beta2-AR (nadolol) or
      beta3-AR (L-748337 or SR 59230A) antagonists but was significantly reduced by
      high concentrations of CGP 20712A (P<0.05). This relaxation was also reduced by
      adenylyl cyclase inhibitors, SQ 22536 or MDL 12330A. 4 In SHR, CGP 12177 produced
      mainly an endothelium and NO-dependent relaxation. This effect was not modified
      by nadolol, but was strongly reduced by beta3-AR blockade. Endothelium
      independent relaxation to CGP 12177 was not altered by adenylyl cyclase
      inhibition, but was amplified in preparations from pertussis toxin-pretreated
      SHR. 5 The immunohistochemical analysis revealed an upregulation of beta3-AR in
      the endothelial layer of SHR aorta, whereas the beta3-AR-induced relaxation was
      not modified. 6 In conclusion, we demonstrated an impaired low-affinity state of
      the beta1-AR-induced relaxation and an upregulation of the beta3-AR in
      hypertension. Some clinical implications of those findings are discussed.

PMID- 15466444
TI  - Mechanisms of beta 3-adrenoceptor-induced eNOS activation in right atrial and
      left ventricular human myocardium.
AB  - beta-Adrenoceptors are important modulators of cardiac function. The present
      study investigated beta(3)-adrenergic eNOS activation in human myocardium. We
      measured nitric oxide (NO) liberation (diaminofluorescence) and signal
      transduction (immunohistochemistry, phosphorylation of eNOS(Ser1177),
      eNOS(Thr495), eNOS(Ser114), Akt/protein kinase B (Akt/PKB), and eNOS
      translocation) in human right atrial (RA, aortocoronary-bypass OP) and left
      ventricular nonfailing (LV, rejected donor hearts) myocardium after application
      of BRL 37344 (BRL), a preferential beta(3)-adrenoceptor agonist. In both RA and
      LV, BRL (10 microl) induced a liberation of NO. An eNOS activation via
      translocation was only observed in RA after application of BRL (10 microM). Yet,
      the NO liberation in both LV and RA was accompanied by phosphorylation of
      eNOS(Ser1177) and Akt/PKB. BRL-induced eNOS phosphorylation was abolished by
      LY292004, a blocker of PI-3 kinase. eNOS-Ser(114) phosphorylation was unchanged
      in RA, but decreased in LV after beta(3)-adrenergic stimulation. BRL did not
      alter phosphorylation of eNOS(Thr495). In conclusion, receptor-dependent eNOS
      activation is differentially regulated in the human heart. In the left ventricle,
      eNOS activation via phosphorylation seems to be of major importance, whereas in
      human atrial myocardium eNOS translocation is the predominant mechanism induced
      by beta(3)-adrenergic activation.

PMID- 15466445
TI  - Macroscopic, microscopic and biochemical characterisation of spontaneous colitis
      in a transgenic mouse, deficient in the multiple drug resistance 1a gene.
AB  - 1 A novel animal model of spontaneous colonic inflammation, the multiple drug
      resistant (mdr1) a(-/-) mouse, was identified by Panwala and colleagues in 1998.
      The aim of our study was to further characterise this model, specifically by
      measuring cytokines that have been implicated in inflammatory bowel disease (IBD)
      (IL-8 and IFN-gamma) in the colon/rectum of mdr1a(-/-) mice, and by determining
      the sensitivity of these, together with the macroscopic, microscopic and disease
      signs of colitis, to dexamethasone (0.05, 0.3 and 2 mg kg(-1) subcutaneously
      (s.c.) daily for 7 days). 2 All mdr1a(-/-) mice had microscopic evidence of
      inflammation in the caecum and colon/rectum, while control mice with the same
      genetic background did not. Significant increases in colon/rectum and caecal
      weights and also in cytokine levels (both IFN-gamma and IL-8) in homogenised
      colon/rectum were observed in mdr1a(-/-) mice compared to mdr1a(+/+) mice. 3
      Dexamethasone reduced the increases in tissue weights and also microscopic
      grading of colitis severity, but had no effect on IFN-gamma or IL-8. 4 This study
      supports the similarity of the gastrointestinal inflammation present in mdr1a(-/
      ) mice to that of human IBD, in particular Crohn's disease. This has been
      demonstrated at the macroscopic and microscopic levels, and was supported further
      by elevations in colonic levels of IFN-gamma and IL-8 and the disease signs
      observed. The incidence of colitis was much higher than previously reported, with
      all mice having microscopic evidence of colitis. The limited variance between
      animals in the parameters measured suggests that this model is reproducible.

PMID- 15466446
TI  - Heterologous desensitization of the sphingosine-1-phosphate receptors by
      purinoceptor activation in renal mesangial cells.
AB  - 1 Sphingosine-1-phosphate (S1P) is considered a potent mitogen for mesangial
      cells and activates the classical mitogen-activated protein kinase (MAPK) cascade
      via S1P receptors. In this study, we show that S1P signalling is rapidly
      desensitized upon S1P receptor activation. A complete loss of S1P sensitivity
      occurs after 10 min of S1P pretreatment and remains for at least 8 h. A similar
      desensitization is also seen with the S1P mimetic FTY720-phosphate, but not with
      the nonphosphorylated FTY720, nor with sphingosine or ceramide. 2 Prestimulating
      the cells with extracellular ATP or UTP, which bind to and activate P2Y receptors
      on mesangial cells, a similar rapid desensitization of the S1P receptor occurs,
      suggesting a heterologous desensitization of S1P receptors by P2Y receptor
      activation. Furthermore, adenosine binding to P1 receptors triggers a similar
      desensitization. In contrast, two other growth factors, PDGF-BB and TGFbeta2,
      have no significant effect on S1P-induced MAPK activation. 3 S1P also triggers
      increased inositol trisphosphate (IP3) formation, which is completely abolished
      by S1P pretreatment but only partially by ATP pretreatment, suggesting that IP3
      formation and MAPK activation stimulated by S1P involve different receptor
      subtypes. 4 Increasing intracellular cAMP levels by forskolin pretreatment has a
      similar effect on desensitization as adenosine. Moreover, a selective A3
      adenosine receptor agonist, which couples to phospholipase C and increases IP3
      formation, exerted a similar effect. 5 Pretreatment of cells with various protein
      kinase C (PKC) inhibitors prior to ATP prestimulation and subsequent S1P
      stimulation leads to a differential reversal of the ATP effect. Whereas the broad
      spectrum protein kinase inhibitor staurosporine potently reverses the effect, the
      PKC-alpha inhibitor CGP41251, the PKC-delta inhibitor rottlerin and calphostin C
      show only a partial reversal at maximal concentrations. 6 Suramin, which is
      reported as a selective S1P3 receptor antagonist compared to the other S1P
      receptor subtypes, has no effect on the S1P-induced MAPK activation, thus
      excluding the involvement of S1P3 in this response. 7 In summary, these data
      document a rapid homologous and also heterologous desensitization of S1P
      signalling in mesangial cells, which is mechanistically triggered by PKC
      activation and eventually another staurosporine-sensitive protein kinase, as well
      as by increased cAMP formation.

PMID- 15466447
TI  - Pharmacological effects of carcinine on histaminergic neurons in the brain.
AB  - 1 Carcinine (beta-alanyl histamine) is an imidazole dipeptide. The present study
      was designed to characterize the pharmacological effects of carcinine on
      histaminergic activity in the brain and on certain neurobehavior. 2 Carcinine was
      highly selective for the histamine H3 receptor over H1 or H2 receptor (Ki
      (microM)=0.2939+/-0.2188 vs 3621.2+/-583.9 or 365.3+/-232.8 microM,
      respectively). 3 Carcinine at a dose of 20 mg kg(-1) slightly increased histidine
      decarboxylase (HDC) activity in the cortex (from 0.186+/-0.069 to 0.227+/-0.009
      pmol mg protein(-1) min(-1)). In addition, carcinine (10, 20, and 50 mg kg(-1))
      significantly decreased histamine levels in mice brain. 4 Like thioperamide, a
      histamine H3 receptor antagonist, carcinine (20, 50 microM) significantly
      increased 5-HT release from mice cortex slices, but had no apparent effect on
      dopamine release. 5 Carcinine (20 mg kg(-1)) significantly inhibited
      pentylenetetrazole-induced kindling. This inhibition was completely reversed by
      (R)-alpha-methylhistamine, a representative H3 receptor agonist, and alpha
      fluromethylhistidine, a selective HDC inhibitor. 6 Carcinine (20 mg kg(-1))
      ameliorated the learning deficit induced by scopolamine. This amelioration was
      reversed by (R)-alpha-methylhistamine as evaluated by the passive avoidance test
      in mice. 7 Like thioperamide, carcinine dose-dependently increased mice locomotor
      activity in the open-field test. 8 The results of this study provide first and
      direct evidence that carcinine, as a novel histamine H3 receptor antagonist,
      plays an important role in histaminergic neurons activation and might be useful
      in the treatment of certain diseases, such as epilepsy, and locomotor or
      cognitive deficit.

PMID- 15466448
TI  - Acute wake-promoting actions of JNJ-5207852, a novel, diamine-based H3
      antagonist.
AB  - 1 1-[4-(3-piperidin-1-yl-propoxy)-benzyl]-piperidine (JNJ-5207852) is a novel,
      non-imidazole histamine H3 receptor antagonist, with high affinity at the rat
      (pKi=8.9) and human (pKi=9.24) H3 receptor. JNJ-5207852 is selective for the H3
      receptor, with negligible binding to other receptors, transporters and ion
      channels at 1 microm. 2 JNJ-5207852 readily penetrates the brain tissue after
      subcutaneous (s.c.) administration, as determined by ex vivo autoradiography
      (ED50 of 0.13 mg kg(-1) in mice). In vitro autoradiography with 3H-JNJ-5207852 in
      mouse brain slices shows a binding pattern identical to that of 3H-R-alpha
      methylhistamine, with high specific binding in the cortex, striatum and
      hypothalamus. No specific binding of 3H-JNJ-5207852 was observed in brains of H3
      receptor knockout mice. 3 In mice and rats, JNJ-5207852 (1-10 mg kg(-1) s.c.)
      increases time spent awake and decreases REM sleep and slow-wave sleep, but fails
      to have an effect on wakefulness or sleep in H3 receptor knockout mice. No
      rebound hypersomnolence, as measured by slow-wave delta power, is observed. The
      wake-promoting effects of this H3 receptor antagonist are not associated with
      hypermotility. 4 A 4-week daily treatment of mice with JNJ-5207852 (10 mg kg(-1)
      i.p.) did not lead to a change in body weight, possibly due to the compound being
      a neutral antagonist at the H3 receptor. 5 JNJ-5207852 is extensively absorbed
      after oral administration and reaches high brain levels. 6 The data indicate that
      JNJ-5207852 is a novel, potent and selective H3 antagonist with good in vitro and
      in vivo efficacy, and confirm the wake-promoting effects of H3 receptor
      antagonists.

PMID- 15466449
TI  - Evidence for P2Y1, P2Y2, P2Y6 and atypical UTP-sensitive receptors coupled to
      rises in intracellular calcium in mouse cultured superior cervical ganglion
      neurons and glia.
AB  - 1 P2Y receptors are expressed in the nervous system and are involved in calcium
      signalling in neurons and glia. In the superior cervical ganglion (SCG), RT-PCR
      analysis indicated the presence of P2Y(1,2&6) receptors. Rises in intracellular
      calcium in response to P2Y receptor stimulation were determined from adult mouse
      cultured SCG neurons and glia. 2 ADP evoked suramin (100 microM)- and
      pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 30 microM)
      sensitive rises in intracellular calcium in approximately 80% of SCG neurons
      (EC50 approximately 20 microM). ADP-evoked responses were abolished in neurons
      from P2Y1 receptor-deficient mice (responses to UTP were unaffected). 3 The
      pyrimidines UTP (EC50 approximately 85 microM) and UDP (EC50>90 microM) evoked
      PPADS- and suramin-sensitive responses in approximately 70 and approximately 20%
      of SCG neurons, respectively. 4 In SCG glial cells, ADP (EC50 approximately 30
      microM) evoked calcium responses in approximately 50% of glia. These were suramin
      and PPADS sensitive and essentially abolished in SCG glial cells cultured from
      adult P2Y1 receptor-deficient mice. 5 UTP (EC50 approximately 25 microM) and UDP
      (EC50>200 microM) evoked suramin- and pyridoxalphosphate-6-azophenyl-2',5'
      disulphonate-sensitive rises in calcium in approximately 60 and 20% SCG glial
      cells, respectively. 6 These results indicate the presence of several P2Y
      receptors coupled to an increase in intracellular calcium in the SCG: ADP
      sensitive P2Y1 receptors and UDP-sensitive P2Y6 receptors in SCG neurons and
      glial cells, a novel UTP-sensitive P2Y receptor in SCG neurons and UTP- and ATP
      sensitive P2Y2 receptors in SCG glia.

PMID- 15466450
TI  - The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in
      vitro and in vivo.
AB  - 1 Tegaserod (Zelnorm) is a potent 5-hydroxytryptamine4 (5-HT4) receptor agonist
      with clinical efficacy in disorders associated with reduced gastrointestinal
      motility and transit. The present study investigated the interaction of tegaserod
      with 5-HT2 receptors, and compared its potency in this respect to its 5-HT4
      receptor agonist activity. 2 Tegaserod had significant binding affinity for human
      recombinant 5-HT2A, 5-HT2B and 5-HT2C receptors (pKi=7.5, 8.4 and 7.0,
      respectively). The 5-HT2B receptor-binding affinity of tegaserod was identical to
      that at human recombinant 5-HT4(c) receptors (mean pKi=8.4) in human embryonic
      kidney-293 (HEK-293) cells stably transfected with the human 5-HT4(c) receptor. 3
      Tegaserod (0.1-3 microm) inhibited 5-HT-mediated contraction of the rat isolated
      stomach fundus potently (pA2=8.3), consistent with 5-HT(2B) receptor antagonist
      activity. Tegaserod produced, with similar potency, an elevation of adenosine
      3',5' cyclic monophosphate in HEK-293 cells stably transfected with the human 5
      HT4(c) receptor (mean pEC50=8.6), as well as 5-HT4) receptor-mediated relaxation
      of the rat isolated oesophagus (mean pEC50=8.2) and contraction of the guinea-pig
      isolated colon (mean pEC50=8.3). 4 Following subcutaneous administration,
      tegaserod (0.3 or 1 mg kg(-1)) inhibited contractions of the stomach fundus in
      anaesthetized rats in response to intravenous dosing of alpha-methyl 5-HT (0.03
      mg kg(-1)) and BW 723C86 (0.3 mg kg(-1)), selective 5-HT2B receptor agonists. At
      similar doses, tegaserod (1 and 3 mg kg(-1) subcutaneously) evoked a 5-HT4
      receptor-mediated increase in colonic transit in conscious guinea-pigs. 5 The
      data from this study indicate that tegaserod antagonizes 5-HT2B receptors at
      concentrations similar to those that activate 5-HT4 receptors. It remains to be
      determined whether this 5-HT2B receptor antagonist activity of tegaserod
      contributes to its clinical profile.

PMID- 15466451
TI  - The melanocortin receptor subtypes in chicken have high preference to ACTH
      derived peptides.
AB  - 1 Melanocortin (MC) receptors are widely distributed throughout the body of
      chicken, like in mammals, and participate in a wide range of physiological
      functions. 2 To clarify the pharmacological impact of ligands acting in the MC
      system, we expressed the chicken MC1, MC2, MC3, MC4 and MC5 (cMC1-5) receptors in
      eukaryotic cells and performed comprehensive pharmacological characterization of
      the potency of endogenous and synthetic melanocortin peptides. 3 Remarkably, the
      cMC receptors displayed high affinity for ACTH-derived peptides and in general
      low affinity for alpha-MSH. It is evident that not only the cMC2 receptor but
      also the other cMC receptors interact with ACTH-derived peptide through an
      epitope beyond the sequence of alpha-MSH. 4 The synthetic ligand MTII was found
      to be a potent agonist whereas HS024 was a potent antagonist at the cMC4
      receptor, indicating that these ligands are suitable for physiological studies in
      chicken. 5 We also show the presence of prohormone convertase 1 (PC1) and PC2
      genes in chicken, and that these peptides are coexpressed with
      proopiomelanocortin (POMC) in various tissues.

PMID- 15466452
TI  - Constitutive expression of CXCL2/MIP-2 is restricted to a Gr-1high, CD11b+,
      CD62Lhigh subset of bone marrow derived granulocytes.
AB  - CXCL2/macrophage inflammatory protein (MIP)-2 is an inducible murine chemokine
      involved in attraction of polymorphonuclear granulocytes to sites of infection.
      In comparison, its role as constitutive produced chemokine in mice is unclear.
      The present study aimed to specify the cellular source of constitutively produced
      CXCL2/MIP-2 and to examine its expression pattern in comparison to other
      chemokines in peripheral lymphoid tissues as well as bone marrow (BM) of normal
      mice. The results showed that constitutive expression of CXCL2/MIP-2 mRNA was
      restricted to BM. As revealed by RT-PCR and FACS analysis, CXCL2/MIP-2 production
      was restricted to a specialized subset of BM derived Gr-1(high) granulocytes.
      This subset was characterized by surface expression of CD11b(+), CD62L(high) and
      CXCR2(+) and accounted for 4-6% of total BM cells. In vitro stimulation of BM
      cells did not increase the number of CXCL2/MIP-2(+) granulocytes. Intracellular
      CXCL2/MIP-2 was not strictly correlated to surface expression of its receptor, as
      the majority of the CXCR2(+)/Gr-1(high) cells lacked CXCL2/MIP-2 staining. In
      controls, CXCL1/KC expression was not detected in BM but was found in peripheral
      tissues in the absence of CXCL2/MIP-2. Together, our results show that CXCL2/MIP
      2 and CXCL1/KC are differentially expressed in a tissue specific manner in normal
      mice and that CXCL2/MIP-2 is produced in a well-defined CD11b(+), CD62L(high), Gr
      1(high) subset of BM granulocytes, thereby providing a possible explanation for
      the independent regulation of both chemokines.

PMID- 15466453
TI  - Crucial role of FOXP3 in the development and function of human CD25+CD4+
      regulatory T cells.
AB  - Naturally occurring CD25(+)CD4(+) regulatory T cells are engaged in the
      maintenance of immunological self-tolerance and down-regulation of various immune
      responses. Recent studies with mice showed that Foxp3, which encodes the
      transcription factor Scurfin, is a master regulatory gene for the development and
      function of CD25(+)CD4(+) regulatory T cells. Here we examined the role of FOXP3
      in human CD25(+)CD4(+) regulatory T cells. The FOXP3 gene and its protein product
      were preferentially expressed in peripheral CD25(+)CD4(+) T cells, in particular
      CD25(+)CD45RO(+)CD4(+) T cells in normal individuals and, interestingly, in some
      human T cell leukemia virus type 1-infected T cell lines, which constitutively
      express CD25. TCR stimulation of CD25(-)CD45RO(-)CD4(+) naive T cells failed to
      elicit FOXP3 expression at the gene or protein level. Ex vivo retroviral gene
      transfer of FOXP3, on the other hand, converted peripheral CD25(-)CD45RO(-)CD4(+)
      naive T cells into a regulatory T cell phenotype similar to CD25(+)CD4(+)
      regulatory T cells. For example, FOXP3-transduced T cells exhibited impaired
      proliferation and production of cytokines including IL-2 and IL-10 upon TCR
      stimulation, up-regulated the expression of regulatory T cell-associated
      molecules such as CD25 and CTL-associated antigen-4 and suppressed in vitro
      proliferation of other T cells in a cell-cell contact-dependent manner. Thus,
      human FOXP3 is a crucial regulatory gene for the development and function of
      CD25(+)CD4(+) regulatory T cells, and can be used as their reliable marker.
      Furthermore, regulatory T cells de novo produced from normal naive T cells by
      FOXP3 transduction can be instrumental for treatment of autoimmune/inflammatory
      diseases and negative control of various immune responses.

PMID- 15466454
TI  - Recall antigen activation induces prompt release of CCR5 ligands from PBMC:
      implication in memory responses and immunization.
AB  - CCR5 ligands RANTES, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta
      are potent and specific inhibitors of strains of human immunodeficiency virus
      (HIV) that use CCR5 as a receptor, which are the strains most involved in primary
      infection. Recently, we observed that release of CCR5 ligands is a consistent and
      reproducible parameter of response to antigen activation in studies using PBMC.
      In this study, we show that CCR5 ligands are released upon antigen [Fragment C of
      tetanus toxin (TTC)] stimulation in 81% (n = 16) of subjects tested, as detected
      by a standard ELISA in tissue culture supernatants of antigen-activated cells. In
      contrast, ELISA for other cytokines from the same supernatants revealed that IFN
      gamma release could be detected only in 31% of subjects, IL-2 could be detected
      only in 12% of the subjects and IL-4 was not detectable in any of the subjects
      tested. Similarly, proliferative responses to TTC, as measured by a standard
      tritiated thymidine incorporation assay, were detectable in only 56% of the
      subjects. Similar observations have been reported in flow cytometric studies, and
      resonate with previous findings emphasizing the role of CCR5 in T cell responses.
      In addition, the levels of CCR5 ligands in supernatants from antigen-activated
      cells were sufficient to inhibit infection of R5 HIV. Thus, CCR5 ligands might
      play a role in controlling HIV in vivo. Taken together, these observations
      suggest that CCR5 ligands, and in particular MIP-1alpha and MIP-1beta, released
      in the course of memory responses may play a role in protecting CD4(+) memory T
      cells from infection.

PMID- 15466455
TI  - Neuronal activity-related coupling in cortical arterioles: involvement of
      astrocyte-derived factors.
AB  - Neuronal activity-evoked dilatation was investigated in cortical arterioles in
      brain slices from mature rats maintained in vitro at 31-33 degrees C. In the
      presence of the thromboxane A2 agonist U46619 (75 nM) to preconstrict vessels,
      internal diameter decreased by 14.2% and rhythmic contractile activity
      (vasomotion) developed. Addition of the epoxygenase inhibitor miconazole (20
      microm) produced a further decrease in diameter and increase in the frequency of
      vasomotion, suggesting that tonic release of epoxygenase products maintains a
      level of cerebrovascular dilator tone. Addition of 1 mum AMPA for 5 min evoked a
      15.4 +/- 3.7% increase in diameter and the frequency of vasomotion decreased by 
      6.7 +/- 1.4 contractions min(-1). The response persisted in the presence of 1 mum
      TTX, indicating that it was independent of neuronal activity and thus likely to
      have been evoked by activation of AMPA receptors on astrocytes rather than
      neurones. The response to the brief (5 min) application of AMPA remained
      unchanged in the presence of miconazole (20 microm). Prolonged (30 min)
      application of AMPA produced a +12.1 +/- 1.5% increase in internal diameter and
      reduction in vasomotion (-8.4 +/- 1.7 contractions min(-1)) that were sustained
      throughout the stimulation period. However, when AMPA was applied in the presence
      of miconazole (20 microm) it evoked only a transient increase in diameter (+9.8
      +/- 3.1%) and decrease in vasomotion (-6.6 +/- 1.5 contractions min(-1)) that
      lasted for less than 10 min despite continued application of AMPA. The results
      suggest that products of epoxygenase activity, probably epoxyeicosatrienoic acids
      (EETs) are involved in activity-related dilatation in cortical arterioles. Whilst
      epoxygenase activity is not required to initiate dilatation, it appears to be
      involved in sustaining the response. Thus EETs released from membrane stores
      could contribute to the initial stages, but once these have been depleted de novo
      synthesis of EETs is required to maintain the effect.

PMID- 15466456
TI  - Ascending aortic stenosis selectively increases action potential-induced Ca2+
      influx in epicardial myocytes of the rat left ventricle.
AB  - A decrease of the transient outward potassium current (Ito) has been observed in
      cardiac hypertrophy and contributes to the altered shape of the action potential
      (AP) of hypertrophied ventricular myocytes. Since the shape and duration of the
      ventricular AP are important determinants of the Ca2+ influx during the AP (QCa),
      we investigated the effect of ascending aortic stenosis (AS) on QCa in endo- and
      epicardial myocytes of the left ventricular free wall using the AP voltage-clamp
      technique. In sham-operated animals, QCa was significantly larger in endocardial
      compared to epicardial myocytes (803 +/- 65 fC pF(-1), n = 27 vs. 167 +/- 32 fC
      pF(-1), n = 38, P < 0.001). Ascending aortic stenosis significantly increased QCa
      in epicardial myocytes (368 +/- 54 fC pF(-1), n = 42, P < 0.05), but did not
      alter QCa in endocardial myocytes (696 +/- 65 fC pF(-1), n = 26). Peak and
      current-voltage relation of the AP-induced Ca2+ current were unaffected by AS.
      However, the time course of the current-voltage relation was significantly
      prolonged in epicardial myocytes of AS animals. Model calculations revealed that
      the increase in QCa can be ascribed to a prolonged opening of the activation
      gate, whereas an increase in inactivation prevents an excessive increase in QCa.
      In conclusion, AS significantly increased AP-induced Ca2+ influx in epicardial
      but not in endocardial myocytes of the rat left ventricle.

PMID- 15466457
TI  - Pregnancy influences the plasma cytokine response to intraperitoneal
      administration of bacterial endotoxin in rats.
AB  - Rats have an attenuated febrile response to intraperitoneal (i.p.) administration
      of exogenous pyrogen (e.g. bacterial endotoxin) near the term of pregnancy. To
      investigate possible mechanisms of this unique thermoregulatory response, the
      present experiments were carried out on 18 non-pregnant and 16 near-term pregnant
      Sprague-Dawley rats to test the hypothesis that pregnancy alters the balance of
      pyrogenic cytokines and antipyretic and/or cryogenic (antipyretic/cryogenic)
      cytokines in response to exogenous pyrogen. To test our hypothesis, we measured
      plasma levels of interleukin (IL)-1beta, IL-6, interleukin-1 receptor antagonist
      (IL-1ra) and tumour necrosis factor alpha(TNFalpha) at 2 and 4 h following i.p.
      administration of 160 microg kg(-1) E. coli lipopolysaccharide (LPS) (i.e. EC100
      dose, or the smallest dose that elicits a maximal febrile response in non
      pregnant rats) in non-pregnant as well as pregnant rats at day 20 of gestation
      (term approximately 21 days). In non-pregnant rats, E. coli LPS elicited
      statistically significant increases in plasma concentrations of IL-1beta, IL-6,
      IL-1ra and TNFalpha as compared to that observed following administration of
      vehicle. However in pregnant rats, E. coli LPS elicited statistically significant
      increases in antipyretic/cryogenic cytokines (IL-1ra and TNFalpha) but not in
      pyrogenic cytokines (IL-1beta and IL-6). Thus, a differential pyrogenic and
      antipyretic/cryogenic plasma cytokine response may mediate in part the attenuated
      febrile response to exogenous pyrogen observed in rats near the term of
      pregnancy.

PMID- 15466458
TI  - Cardiovascular responses to orthostatic stress in healthy altitude dwellers, and
      altitude residents with chronic mountain sickness.
AB  - High altitude (HA) dwellers have an exceptionally high tolerance to orthostatic
      stress, and this may partly be related to their high packed cell and blood
      volumes. However, it is not known whether their orthostatic tolerance would be
      changed after relief of the altitude-related hypoxia. Furthermore, orthostatic
      tolerance is known also to be influenced by the efficiency of the control of
      peripheral vascular resistance and by the effectiveness of cerebral
      autoregulation and these have not been reported in HA dwellers. In this study we
      examined plasma volume, orthostatic tolerance and peripheral vascular and
      cerebrovascular responses to orthostatic stress in HA dwellers, including some
      with chronic mountain sickness (CMS) in whom packed cell and blood volumes are
      particularly large. Eleven HA control subjects and 11 CMS patients underwent
      orthostatic stress testing, comprising head-up tilting with lower body suction,
      at their resident altitude (4338 m) and at sea level. Blood pressure (Portapres),
      heart rate (ECG), brachial and middle cerebral artery blood velocities (Doppler)
      were recorded during the test. Plasma volumes were found to be similar in both
      groups and at both locations. Packed cell and blood volumes were higher in CMS
      patients than controls. All subjects had very good orthostatic tolerances at both
      locations, compared to previously published data in lowland dwellers. In CMS
      patients responses of forearm vascular resistance to the orthostatic stress, at
      sea level, were smaller than controls (P < 0.05). Cerebral blood velocity was
      less in CMS than in controls (P < 0.01) and, at sea level, it decreased more than
      the controls in response to head-up tilting (P < 0.02). Cerebral autoregulation,
      assessed from the relationship between cerebral pressure and velocity, was also
      impaired in CMS patients compared to HA controls, when examined at sea level (P <
      0.02). These results have shown that the good orthostatic tolerance seen in high
      altitude dwellers at altitude is also seen at sea level. There was no difference
      in orthostatic tolerance between CMS patients, with their exceptionally large
      blood volumes, and the HA controls. This may be because peripheral vascular and
      cerebrovascular responses (at least at sea level) are impaired in the CMS
      patients relative to HA controls. Thus, the advantage of the large blood volume
      may be offset by the smaller vascular responses.

PMID- 15466459
TI  - Effect of oestrogen on myofibre size and myosin expression in growing rats.
AB  - This study examined the effect of oestrogen deprivation and replacement on
      plantaris muscle size and myosin heavy chain (MHC) isoform composition in rats
      during a period of physiological growth. Seven-week-old female Sprague-Dawley
      rats were assigned to one of the three treatment groups: (1) control animals
      (Sham); (2) ovariectomized animals without oestrogen replacement (OVX/CO); and
      (3) ovariectomized animals with 17beta-oestradiol replacement (OVX/E2). OVX/CO
      and OVX/E2 animals were pair-fed with Sham animals to rule out the potentially
      confounding effects of differences in food intake and weight gain. Rats were
      killed 4 weeks after surgery and the plantaris muscle was removed for analysis.
      Ovariectomy had no effect on muscle fibre size, but reduced the relative amount
      of type IIx MHC. This was reversed with oestrogen replacement, suggesting that
      the reduction in type IIx MHC expression was an oestrogen-mediated effect.
      Oestrogen replacement reduced type IIb MHC expression and fast muscle fibre size.
      Changes in fast fibre size and type IIb MHC expression were not seen with
      ovariectomy, indicating that these changes were not simply due to the presence of
      oestrogen in the ovariectomized, oestrogen-replaced animals. These results
      suggest that another ovarian hormone may counteract the effect of oestrogen on
      fast fibre size and type IIb MHC expression in intact animals.

PMID- 15466460
TI  - The role of exercise on long-term effects of alloxan administered in neonatal
      rats.
AB  - The present study was designed to analyse the effects of aerobic exercise on the
      metabolic effects of alloxan. Male Wistar newborn rats (2 days old) received
      alloxan (200 mg (kg body weight)(-1)) intraperitoneally (A rats). Vehicle
      injected rats were used as controls (C rats). At 28 days old, some of the A rats
      were subjected to swimming for 1 h day(-1), 5 day week(-1) (AT rats). At 28, 60
      and 90 days old the animals were subjected to glucose (GTTo) and insulin (ITTsc)
      tolerance tests. All the animals were then killed by decapitation for blood and
      tissue evaluations. On the 60th day, there was a reduction in blood glucose level
      during the GTTo (mmol l(-1) (90 min)(-1)) in the AT rats (7640.7 +/- 694.0) with
      respect to C (7057.5 +/- 776.9) and A (8555.6 +/- 1096.7) rats. However on the
      90th day, AT rats showed higher glucose levels (8004.6 +/- 267.9) when compared
      to the other groups (C, 7305.5 +/- 871.2; A, 7088.8 +/- 536.9). The serum free
      fatty acid (FFA) concentration (microEq l(-1)) was higher in the alloxan-treated
      animals (A, 231.1 +/- 58.5; AT, 169.8 +/- 20.1) than in controls (C, 101.4 +/-
      22.4). In conclusion, although the high blood glucose level is transitory in the
      A animals, some blood and tissue alterations remain and can be harmful to the
      maintenance of homeostasis. Physical exercise counteracted only partially these
      alterations. Furthermore, training worsened glucose tolerance at the 90th day,
      suggesting that exercise intensity should be adjusted to the diabetic condition.

PMID- 15466461
TI  - Comparison of effects of acetylcholine on electromechanical characteristics in
      guinea-pig atrium and ventricle.
AB  - The direct negative effects of acetylcholine (ACh) on guinea-pig atria and
      ventricles were investigated using standard microelectrodes, a force transducer
      and a video edge-detection system. It was found that: (1) ACh (at 0.001-100
      microm) decreased the force of contraction and shortened the action potential
      duration (APD) in both atria and ventricles in a concentration-dependent manner,
      and that the atria were more sensitive to ACh than the ventricles; and (2) the
      direct negative inotropic effect of ACh (1 microm) on an isolated cardiac cell
      was similar to that on the isolated myocardium. But this effect was not present
      in all isolated ventricular cells, while all the atrial cells responded to ACh.
      In conclusion, ACh had direct inhibitory effects on both atrial and ventricular
      tissue and myocytes, although the effects were greater in atria than in
      ventricles; and the negative inotropic effect of ACh was closely related to the
      shortening of the APD.

PMID- 15466462
TI  - Insight of host immune evasion mediated by two variants of group a Streptococcus
      Mac protein.
AB  - Group A Streptococcus has evolved numerous mechanisms to evade the host immune
      system to survive, disseminate, and cause disease. Recently a secreted protein
      named Mac-1 was identified and shown to enhance survival of the pathogen. A new
      variant of Mac-1 (designated Mac-2) also was recently described and shown to
      differ from Mac-1 by approximately 50% amino acid sequence divergence in the
      middle one-third of the molecule. To gain new information about the role of Mac-1
      and Mac-2 in host-pathogen interactions, solution binding experiments were
      performed using surface plasmon resonance and purified Mac proteins. Mac-1 bound
      the same lower hinge region of human IgG as Fc receptors with 2.5 microM
      affinity, which lead to proteolytic cleavage of the antibody. Similar Km (6.8
      18.9 microM) and kcat (0.02-0.13 s(-1)) values of the Mac-1 endopeptidase
      activity were obtained for IgG1, IgG2, IgG3, and IgG4. Mac-2 variant, in
      contrast, bound human IgG poorly (KD = 16 mM) and had weak endopeptidase activity
      against IgG. Instead, Mac-2 bound FcgammaRII and FcgammaRIII with 5 and 75 microM
      affinity, respectively. This binding competitively blocked IgG from recognition
      by Fc receptors. Taken together, Mac proteins block immunoglobulin recognition by
      Fc receptors and degrade immunoglobulins, thereby enhancing survival of the
      pathogen through the inhibition of phagocytosis, endocytosis of IgG-opsonized
      particles, and antibody-dependent cell-mediated cytotoxicity. Consequently, these
      proteins may be potential therapeutic targets.

PMID- 15466463
TI  - Acidocalcisomes and the contractile vacuole complex are involved in
      osmoregulation in Trypanosoma cruzi.
AB  - Trypanosoma cruzi, the etiologic agent of Chagas disease, resists extreme
      fluctuations in osmolarity during its life cycle. T. cruzi possesses a robust
      regulatory volume decrease mechanism that completely reverses cell swelling when
      submitted to hypo-osmotic stress. The efflux of amino acids and K+ release could
      account for only part for this volume reversal. In this work we demonstrate that
      swelling of acidocalcisomes mediated by an aquaporin and microtubule- and cyclic
      AMP-mediated fusion of acidocalcisomes to the contractile vacuole complex with
      translocation of this aquaporin and the resulting water movement are responsible
      for the volume reversal not accounted for by efflux of osmolytes. Contractile
      vacuole bladders were isolated by subcellular fractionation in iodixanol
      gradients, showed a high concentration of basic amino acids and inorganic
      phosphate, and were able to transport protons in the presence of ATP or
      pyrophosphate. Taken together, these results strongly support a role for
      acidocalcisomes and the contractile vacuole complex in osmoregulation and
      identify a functional role for aquaporin in protozoal osmoregulation.

PMID- 15466464
TI  - Estrogen-related receptor alpha (ERRalpha) is a transcriptional regulator of
      apolipoprotein A-IV and controls lipid handling in the intestine.
AB  - The estrogen-related receptor alpha (ERRalpha) is an orphan member of the
      superfamily of nuclear receptors involved in the control of energy metabolism. In
      particular, ERRalpha induces a high energy expenditure in the presence of the
      coactivator PGC-1alpha. However, ERRalpha knockout mice have reduced fat mass and
      are resistant to diet-induced obesity. ERRalpha is expressed in epithelial cells
      of the small intestine, and because the intestine is the first step in the energy
      chain, we investigated whether ERRalpha plays a function in dietary energy
      handling. Gene expression profiling in the intestine identified a subset of genes
      involved in oxidative phosphorylation that were down-regulated in the absence of
      ERRalpha. In support of the physiological role of ERRalpha in this pathway,
      isolated enterocytes from ERRalpha knockout mice display lower capacity for beta
      oxidation. Microarray results also show altered expression of genes involved in
      dietary lipid digestion and absorption, such as pancreatic lipase-related protein
      2 (PLRP2), fatty acid-binding protein 1 and 2 (L-FABP and I-FABP), and
      apolipoprotein A-IV (apoA-IV). In agreement, we found that ERRalpha-/- pups
      exhibit significant lipid malabsorption. We further show that the apoA-IV
      promoter is a direct target of ERRalpha and that its presence is required to
      maintain basal level but not feeding-induced regulation of the apoA-IV gene in
      mice. ERRalpha, in cooperation with PGC-1alpha, activates the apoA-IV promoter
      via interaction with the apoC-III enhancer in both human and mouse. Our results
      demonstrate that apoA-IV is a direct ERRalpha target gene and suggest a function
      for ERRalpha in intestinal fat transport, a crucial step in energy balance.

PMID- 15466465
TI  - Thyroxine-thyroid hormone receptor interactions.
AB  - Thyroid hormone (TH) actions are mediated by nuclear receptors (TRs alpha and
      beta) that bind triiodothyronine (T(3), 3,5,3'-triiodo-l-thyronine) with high
      affinity, and its precursor thyroxine (T(4), 3,5,3',5'-tetraiodo-l-thyronine)
      with lower affinity. T(4) contains a bulky 5' iodine group absent from T(3).
      Because T(3) is buried in the core of the ligand binding domain (LBD), we have
      predicted that TH analogues with 5' substituents should fit poorly into the
      ligand binding pocket and perhaps behave as antagonists. We therefore examined
      how T(4) affects TR activity and conformation. We obtained several lines of
      evidence (ligand dissociation kinetics, migration on hydrophobic interaction
      columns, and non-denaturing gels) that TR-T(4) complexes adopt a conformation
      that differs from TR-T(3) complexes in solution. Nonetheless, T(4) behaves as an
      agonist in vitro (in effects on coregulator and DNA binding) and in cells, when
      conversion to T(3) does not contribute to agonist activity. We determined x-ray
      crystal structures of the TRbeta LBD in complex with T(3) and T(4) at 2.5-A and
      3.1-A resolution. Comparison of the structures reveals that TRbeta accommodates
      T(4) through subtle alterations in the loop connecting helices 11 and 12 and
      amino acid side chains in the pocket, which, together, enlarge a niche that
      permits helix 12 to pack over the 5' iodine and complete the coactivator binding
      surface. While T(3) is the major active TH, our results suggest that T(4) could
      activate nuclear TRs at appropriate concentrations. The ability of TR to adapt to
      the 5' extension should be considered in TR ligand design.

PMID- 15466466
TI  - Growth phase regulation of the main folate transporter of Leishmania infantum and
      its role in methotrexate resistance.
AB  - The protozoan parasite Leishmania relies on the uptake of folate and pterin from
      the environment to meet its nutritional requirements. We show here that a novel
      gene (folate transporter 1 (FT1)) deleted in a Leishmania infantum methotrexate
      resistant mutant corresponds to the main folate transporter (K(m), 410 nM). FT1
      was established as the main folate transporter by both gene transfection and by
      targeted gene deletion. Modulation of the expression of FT1 by these
      manipulations altered the susceptibility of Leishmania cells to methotrexate.
      Folate transport was stage-regulated with higher activity in the logarithmic
      phase and less in the stationary phase. FT1 fused to green fluorescent protein
      led to the observation that FT1 was located in the plasma membrane in the
      logarithmic phase but was retargeted to an intracellular organelle followed by a
      degradation of the protein in stationary phase. Leishmania has several folate
      transporters with different characteristics, and the growth stage-related
      activity of at least one transporter is regulated post-translationally.

PMID- 15466467
TI  - alpha-Synuclein expression levels do not significantly affect proteasome function
      and expression in mice and stably transfected PC12 cell lines.
AB  - alpha-Synuclein (alpha-syn) is a small protein of unknown function that is found
      aggregated in Lewy bodies, the histopathological hallmark of sporadic Parkinson
      disease and other synucleinopathies. Mutations in the alpha-syn gene and a
      triplication of its gene locus have been identified in early onset familial
      Parkinson disease. alpha-Syn turnover can be mediated by the proteasome pathway.
      A survey of published data may lead to the suggestion that overexpression of
      alpha-syn wild type, and/or their variants (A53T and A30P), may produce a
      decrease in proteasome activity and function, contributing to alpha-syn
      aggregation. To investigate the relationship between synuclein expression and
      proteasome function we have studied proteasome peptidase activities and
      proteasome subunit expression (alpha, beta-constitutive, and inducible) in mice
      either lacking alpha-syn (knock-out mice) or transgenic for human alpha-syn A30P
      (under control of PrP promoter, at a time when no clear gliosis can be observed).
      Similar studies are presented in PC12 cells overexpressing enhanced yellow
      fluorescent protein fusion constructs of human wild type, A30P, and A53T alpha
      syn. In these cell lines we have also analyzed the assembly of 20 S proteasome
      complex and the degradation rate of a well known substrate of the proteasome
      pathway, Ikappabalpha. Overall the data obtained led us to the conclusion that
      alpha-synuclein expression levels by themselves have no significant effect on
      proteasome peptidase activity, subunit expression, and proteasome complex
      assembly and function. These results strengthen the suggestion that other
      mechanisms resulting in synuclein aggregation (not simply expression levels) may
      be the key to understand the possible effect of aggregated synuclein on
      proteasome function.

PMID- 15466468
TI  - Enhanced activation of tax-dependent transcription of human T-cell leukemia virus
      type I (HTLV-I) long terminal repeat by TORC3.
AB  - Tax, a protein encoded by the env-pX gene of human T-cell leukemia virus type I
      (HTLV-I), interacts with various host cell transcription factors. Tax activates
      transcription from the long terminal repeat (LTR) of HTLV-I through association
      with cyclic AMP-responsive element-binding protein (CREB). Here, we present
      evidence that transducer of regulated cyclic AMP-response element-binding protein
      3 (TORC3), a co-activator of CREB, is involved in Tax-induced transcriptional
      activation from the HTLV-I LTR. By using a luciferase assay system, we show that
      TORC3 alone can enhance transcription from the HTLV-I LTR, as well as from a
      cellular cyclic AMP-response element (CRE). Interestingly, we find that co
      expression of TORC3 and Tax dramatically increased transcriptional activation at
      the HTLV-I LTR. We also show by glutathione S-transferase pull-down and co
      immunoprecipitation experiments that TORC3 interacts with Tax. Using deletion
      mutant analysis, we identify the Tax interaction domain of TORC3 as a region
      spanning from amino acid 1 to 103, which contains a coiled-coil domain. These
      results provide important clues toward understanding the molecular mechanism of
      Tax-dependent transcriptional activation of the HTLV-I LTR.

PMID- 15466469
TI  - Proteomic analysis of the Drosophila larval hemolymph clot.
AB  - Components of the insect clot, an extremely rapid forming and critical part of
      insect immunity, are just beginning to be identified (1). Here we present a
      proteomic comparison of larval hemolymph before and after clotting to learn more
      about this process. This approach was supplemented by the identification of
      substrates for the enzyme transglutaminase, which plays a role in both vertebrate
      blood clotting (as factor XIIIa) and hemolymph coagulation in arthropods.
      Hemolymph proteins present in lower amounts after clotting include CG8502 (a
      protein with a mucin-type domain and a domain with similarity to cuticular
      components), CG11313 (a protein with similarity to prophenoloxidase-activating
      proteases), and two phenoloxidases, lipophorin, a secreted gelsolin, and CG15825,
      which had previously been isolated from clots (2). Proteins whose levels increase
      after clotting include a ferritin-subunit and two members of the immunoglobulin
      family with a high similarity to the small immunoglobulin-like molecules involved
      in mammalian innate immunity. Our results correlate with findings from another
      study of coagulation (2) that involved a different experimental approach.
      Proteomics allows the isolation of novel candidate clotting factors, leading to a
      more complete picture of clotting. In addition, our two-dimensional protein map
      of cell-free Drosophila hemolymph includes many additional proteins that were not
      found in studies performed on whole hemolymph.

PMID- 15466470
TI  - Molecular determinants of substrate recognition in hematopoietic protein-tyrosine
      phosphatase.
AB  - The extracellular signal-regulated protein kinase 2 (ERK2) plays a central role
      in cellular proliferation and differentiation. Full activation of ERK2 requires
      dual phosphorylation of Thr183 and Tyr185 in the activation loop. Tyr185
      dephosphorylation by the hematopoietic protein-tyrosine phosphatase (HePTP)
      represents an important mechanism for down-regulating ERK2 activity. The
      bisphosphorylated ERK2 is a highly efficient substrate for HePTP with a kcat/Km
      of 2.6 x 10(6) m(-1) s(-1). In contrast, the kcat/Km values for the HePTP
      catalyzed hydrolysis of Tyr(P) peptides are 3 orders of magnitude lower. To gain
      insight into the molecular basis for HePTP substrate specificity, we analyzed the
      effects of altering structural features unique to HePTP on the HePTP-catalyzed
      hydrolysis of p-nitrophenyl phosphate, Tyr(P) peptides, and its physiological
      substrate ERK2. Our results suggest that substrate specificity is conferred upon
      HePTP by both negative and positive selections. To avoid nonspecific tyrosine
      dephosphorylation, HePTP employs Thr106 in the substrate recognition loop as a
      key negative determinant to restrain its protein-tyrosine phosphatase activity.
      The extremely high efficiency and fidelity of ERK2 dephosphorylation by HePTP is
      achieved by a bipartite protein-protein interaction mechanism, in which docking
      interactions between the kinase interaction motif in HePTP and the common docking
      site in ERK2 promote the HePTP-catalyzed ERK2 dephosphorylation (approximately 20
      fold increase in kcat/Km) by increasing the local substrate concentration, and
      second site interactions between the HePTP catalytic site and the ERK2 substrate
      binding region enhance catalysis (approximately 20-fold increase in kcat/Km) by
      organizing the catalytic residues with respect to Tyr(P)185 for optimal
      phosphoryl transfer.

PMID- 15466471
TI  - The glycoprotein NOWA and minicollagens are part of a disulfide-linked polymer
      that forms the cnidarian nematocyst wall.
AB  - The nematocyst is a unique extrusive organelle involved in the defense and
      capture of prey in cnidarians. Minicollagens and the glycoprotein NOWA are major
      components of the nematocyst capsule wall, which resists osmotic pressure of 15
      MPa. Here we present the recombinant expression of NOWA, which spontaneously
      assembles to globular macromolecular particles that are sensitive to reduction as
      the native wall structure. Ultra-structural analysis showed that the Hydra
      nematocyst wall is composed of several layers of globular particles, which are
      interconnected via radiating rodlike protrusions. Evidence is presented that
      native wall particles contain NOWA and minicollagen, supposed to be linked via
      disulfide bonds between their homologous cysteine-rich domains. Our data suggest
      a continuous suprastructure of the nematocyst wall, assembled from wall proteins
      that share a common oligomerization motif.

PMID- 15466472
TI  - Ubiquitylation of neuronal nitric-oxide synthase by CHIP, a chaperone-dependent
      E3 ligase.
AB  - It is established that neuronal nitric-oxide synthase (nNOS) is ubiquitylated and
      proteasomally degraded. The proteasomal degradation of nNOS is enhanced by
      suicide inactivation of nNOS or by the inhibition of hsp90, which is a chaperone
      found in a native complex with nNOS. In the current study, we have examined
      whether CHIP, a chaperone-dependent E3 ubiquitin-protein isopeptide ligase that
      is known to ubiquitylate other hsp90-chaperoned proteins, could act as an
      ubiquitin ligase for nNOS. We found with the use of HEK293T or COS-7 cells and
      transient transfection methods that CHIP overexpression causes a decrease in
      immunodetectable levels of nNOS. The extent of the loss of nNOS is dependent on
      the amount of CHIP cDNA used for transfection. Lactacystin (10 microM), a
      selective proteasome inhibitor, attenuates the loss of nNOS in part by causing
      the nNOS to be found in a detergent-insoluble form. Immunoprecipitation of the
      nNOS and subsequent Western blotting with an anti-ubiquitin IgG shows an increase
      in nNOS-ubiquitin conjugates because of CHIP. Moreover, incubation of nNOS with a
      purified system containing an E1 ubiquitin-activating enzyme, an E2 ubiquitin
      carrier protein conjugating enzyme (UbcH5a), CHIP, glutathione S-transferase
      tagged ubiquitin, and an ATP-generating system leads to the ubiquitylation of
      nNOS. The addition of purified hsp70 and hsp40 to this in vitro system greatly
      enhances the amount of nNOS-ubiquitin conjugates, suggesting that CHIP is an E3
      ligase for nNOS whose action is facilitated by (and possibly requires) its
      interaction with nNOS-bound hsp70.

PMID- 15466474
TI  - Heterophilic interactions of sodium channel beta1 subunits with axonal and glial
      cell adhesion molecules.
AB  - Voltage-gated sodium channels localize at high density in axon initial segments
      and nodes of Ranvier in myelinated axons. Sodium channels consist of a pore
      forming alpha subunit and at least one beta subunit. beta1 is a member of the
      immunoglobulin superfamily of cell adhesion molecules and interacts
      homophilically and heterophilically with contactin and Nf186. In this study, we
      characterized beta1 interactions with contactin and Nf186 in greater detail and
      investigated interactions of beta1 with NrCAM, Nf155, and sodium channel beta2
      and beta3 subunits. Using Fc fusion proteins and immunocytochemical techniques,
      we show that beta1 interacts with the fibronectin-like domains of contactin.
      beta1 also interacts with NrCAM, Nf155, sodium channel beta2, and Nf186 but not
      with sodium channel beta3. The interaction of the extracellular domains of beta1
      and beta2 requires the region 169TEEEGKTDGEGNA181 located in the intracellular
      domain of beta2. Interaction of beta1 with Nf186 results in increased Nav).2 cell
      surface density over alpha alone, similar to that shown previously for contactin
      and beta2. We propose that beta1 is the critical communication link between
      sodium channels, nodal cell adhesion molecules, and ankyrinG.

PMID- 15466473
TI  - Identification of residues within human glycoprotein VI involved in the binding
      to collagen: evidence for the existence of distinct binding sites.
AB  - Glycoprotein VI (GPVI) has a crucial role in platelet responses to collagen.
      Still, little is known about its interaction with its ligands. In binding assays
      using soluble or cell-expressed human GPVI, we observed that (i) collagen, and
      the GPVI-specific ligands collagen-related peptides (CRP) and convulxin, competed
      with one another for the binding to GPVI and (ii) monoclonal antibodies directed
      against the extracellular part of the human receptor displayed selective
      inhibitory properties on GPVI interaction with its ligands. Monoclonal antibody
      9E18 strongly reduced the binding of GPVI to collagen/CRP, 3F8 inhibited its
      interaction with convulxin, whereas 9O12 prevented all three interactions. These
      observations suggest that ligand-binding sites are distinct, exhibiting specific
      features but at the same time also sharing some common residues participating in
      the recognition of these ligands. The epitope of 9O12 was mapped by phage
      display, along with molecular modeling of human GPVI, which allowed the
      identification of residues within GPVI potentially involved in ligand
      recognition. Site-directed mutagenesis revealed that valine 34 and leucine 36 are
      critical for GPVI interaction with collagen and CRP. The loop might thus be part
      of a collagen/CRP-binding site.

PMID- 15466475
TI  - Induction of CCAAT/enhancer-binding protein (C/EBP)-homologous protein/growth
      arrest and DNA damage-inducible protein 153 expression during inhibition of
      phosphatidylcholine synthesis is mediated via activation of a C/EBP-activating
      transcription factor-responsive element.
AB  - The gene for the proapoptotic transcription factor CCAAT/enhancer-binding protein
      (C/EBP)-homologous protein/growth arrest and DNA damage-inducible protein 153
      (CHOP/GADD153) is induced by various cellular stresses. Previously, we described
      that inhibition of phosphatidylcholine (PC) synthesis in MT58 cells, which
      contain a temperature-sensitive mutation in CTP:phosphocholine
      cytidylyltransferase (CT), results in apoptosis preceded by the induction of
      CHOP. Here we report that prevention of CHOP induction, by expression of
      antisense CHOP, delays the PC depletion-induced apoptotic process. By mutational
      analysis of the conserved region in the promoter of the CHOP gene, we provide
      evidence that the C/EBP-ATF composite site, but not the ER stress-responsive
      element or the activator protein-1 site, is required for the increased expression
      of CHOP during PC depletion. Inhibition of PC synthesis in MT58 cells also led to
      an increase in phosphorylation of the stress-related transcription factor ATF2
      and the stress kinase JNK after 8 and 16 h, respectively. In contrast, no
      phosphorylation of p38 MAPK was observed in MT58 cultured at the nonpermissive
      temperature. Treatment of MT58 cells with the JNK inhibitor SP600125 could rescue
      the cells from apoptosis but did not inhibit the phosphorylation of ATF2 or the
      induction of CHOP. Taken together, our results suggest that increased expression
      of CHOP during PC depletion depends on a C/EBP-ATF element in its promoter and
      might be mediated by binding of ATF2 to this element.

PMID- 15466476
TI  - Phosphorylation of threonine 290 in the activation loop of Tpl2/Cot is necessary
      but not sufficient for kinase activity.
AB  - Cot/Tpl2/MAP3K8 is a serine/threonine kinase known to activate the ERK, p38, and
      JNK kinase pathways. Studies of Tpl2 knock-out mice reveal a clear defect in
      tumor necrosis factor-alpha production, although very little detail is known
      about its regulation and the signaling events involved. In the present study we
      demonstrated that phosphorylation of Cot was required for its maximal activity as
      phosphatase treatment of Cot decreased its kinase activity. The Cot sequence
      contains a conserved threonine at position 290 in the activation loop of the
      kinase domain. We found that mutation of this residue to alanine eliminated its
      ability to activate MEK/ERK and NF-kappaB pathways, whereas a phosphomimetic
      mutation to aspartic acid could rescue the ability to activate MEK. Thr-290 was
      also required for robust autophosphorylation of Cot. Antibody generated to
      phospho-Thr-290-Cot recognized both wild-type and kinase-dead Cot, suggesting
      that phosphorylation of Thr-290 did not occur through autophosphorylation but via
      another kinase. We showed that Cot was constitutively phosphorylated at Thr-290
      in transfected human embryonic kidney 293T cells as well as human monocytes as
      this residue was phosphorylated in unstimulated and lipopolysaccharide-stimulated
      cells to the same degree. Treatment with herbimycin A inhibited Cot activity in
      the MEK/ERK pathway but did not inhibit phosphorylation at Thr-290. Together
      these results showed that phosphorylation of Cot at Thr-290 is necessary but not
      sufficient for full kinase activity in the MEK/ERK pathway.

PMID- 15466477
TI  - Distinct pools of epithelial sodium channels are expressed at the plasma
      membrane.
AB  - The epithelial Na+ channel (ENaC) is assembled in the endoplasmic reticulum from
      three structurally related subunits (alpha, beta, and gamma). Channel maturation
      within the biosynthetic pathway involves cleavage of the alpha and gamma subunits
      by furin and processing of N-linked glycans on alpha, beta, and gamma to complex
      type. Both mature and immature subunits have been observed at the surface of
      stably transfected Madin-Darby canine kidney cells. We have examined whether
      channel maturation is an all-or-none event or whether heterogeneous processing of
      channel subunits occurs within an individual channel complex. Using an
      immobilized lectin to isolate proteins with complex type N-glycans, we found that
      individual channel complexes with mature subunits lack immature subunits.
      Furthermore, terminal processing of N-glycans on ENaC subunits was not dependent
      on cleavage of ENaC subunits, and proteolysis of channel subunits was not
      dependent on prior processing of N-glycans. Our results suggest that processing
      of subunits within an individual channel complex is an all-or-none event such
      that channels present on the cell surface contain either all mature or all
      immature subunits. The presence of immature channel complexes at the plasma
      membrane provides epithelial cells with a reserve of poorly functional channels
      that can be activated by proteases in post-Golgi compartments.

PMID- 15466478
TI  - Leaky beta-oxidation of a trans-fatty acid: incomplete beta-oxidation of elaidic
      acid is due to the accumulation of 5-trans-tetradecenoyl-CoA and its hydrolysis
      and conversion to 5-trans-tetradecenoylcarnitine in the matrix of rat
      mitochondria.
AB  - The degradation of elaidic acid (9-trans-octadecenoic acid), oleic acid, and
      stearic acid by rat mitochondria was studied to determine whether the presence of
      a trans double bond in place of a cis double bond or no double bond affects beta
      oxidation. Rat mitochondria from liver or heart effectively degraded the coenzyme
      A derivatives of all three fatty acids. However, with elaidoyl-CoA as a
      substrate, a major metabolite accumulated in the mitochondrial matrix. This
      metabolite was isolated and identified as 5-trans-tetradecenoyl-CoA. In contrast,
      little or none of the corresponding metabolites were detected with oleoyl-CoA or
      stearoyl-CoA as substrates. A kinetic study of long-chain acyl-CoA dehydrogenase
      (LCAD) and very long-chain acyl-CoA dehydrogenase revealed that 5-trans
      tetradecenoyl-CoA is a poorer substrate of LCAD than is 5-cis-tetradecenoyl-CoA,
      while both unsaturated acyl-CoAs are poor substrates of very long-chain acyl-CoA
      dehydrogenase when compared with myristoyl-CoA. Tetradecenoic acid and
      tetradecenoylcarnitine were detected by gas chromatography/mass spectrometry and
      tandem mass spectrometry, respectively, when rat liver mitochondria were
      incubated with elaidoyl-CoA but not when oleoyl-CoA was the substrate. These
      observations support the conclusion that 5-trans-tetradecenoyl-CoA accumulates in
      the mitochondrial matrix, because it is less efficiently dehydrogenated by LCAD
      than is its cis isomer and that the accumulation of this beta-oxidation
      intermediate facilitates its hydrolysis and conversion to 5-trans
      tetradecenoylcarnitine thereby permitting a partially degraded fatty acid to
      escape from mitochondria. Analysis of this compromised but functional process
      provides insight into the operation of beta-oxidation in intact mitochondria.

PMID- 15466479
TI  - Abnormal lipid metabolism in cystathionine beta-synthase-deficient mice, an
      animal model for hyperhomocysteinemia.
AB  - Hyperhomocysteinemia (HHCY) is a consequence of impaired methionine/cysteine
      metabolism and is caused by deficiency of vitamins and/or enzymes such as
      cystathionine beta-synthase (CBS). Although HHCY is an important and independent
      risk factor for cardiovascular diseases that are commonly associated with hepatic
      steatosis, the mechanism by which homocysteine promotes the development of fatty
      liver is poorly understood. CBS-deficient (CBS(-/-)) mice were previously
      generated by targeted deletion of the Cbs gene and exhibit pathological features
      similar to HHCY patients, including endothelial dysfunction and hepatic
      steatosis. Here we show abnormal lipid metabolism in CBS(-/-) mice. Triglyceride
      and nonesterified fatty acid levels were markedly elevated in CBS(-/-) mouse
      liver and serum. The activity of thiolase, a key enzyme in beta-oxidation of
      fatty acids, was significantly impaired in CBS(-/-) mouse liver. Hepatic
      apolipoprotein B100 levels were decreased, whereas serum apolipoprotein B100 and
      very low density lipoprotein levels were elevated in CBS(-/-) mice. Serum levels
      of cholesterol/phospholipid in high density lipoprotein fractions but not of
      total cholesterol/phospholipid were decreased, and the activity of lecithin
      cholesterol acyltransferase was severely impaired in CBS(-/-) mice. Abnormal high
      density lipoprotein particles with higher mobility in polyacrylamide gel
      electrophoresis were observed in serum obtained from CBS(-/-) mice. Moreover,
      serum cholesterol/triglyceride distribution in lipoprotein fractions was altered
      in CBS(-/-) mice. These results suggest that hepatic steatosis in CBS(-/-) mice
      is caused by or associated with abnormal lipid metabolism.

PMID- 15466480
TI  - MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons.
AB  - Microtubule-dependent transport of vesicles and organelles appears saltatory
      because particles switch between periods of rest, random Brownian motion, and
      active transport. The transport can be regulated through motor proteins, cargo
      adaptors, or microtubule tracks. We report here a mechanism whereby microtubule
      associated proteins (MAPs) represent obstacles to motors which can be regulated
      by microtubule affinity regulating kinase (MARK)/Par-1, a family of kinases that
      is known for its involvement in establishing cell polarity and in phosphorylating
      tau protein during Alzheimer neurodegeneration. Expression of MARK causes the
      phosphorylation of MAPs at their KXGS motifs, thereby detaching MAPs from the
      microtubules and thus facilitating the transport of particles. This occurs
      without impairing the intrinsic activity of motors because the velocity during
      active movement remains unchanged. In primary retinal ganglion cells,
      transfection with tau leads to the inhibition of axonal transport of
      mitochondria, APP vesicles, and other cell components which leads to starvation
      of axons and vulnerability against stress. This transport inhibition can be
      rescued by phosphorylating tau with MARK.

PMID- 15466481
TI  - Disruption of LTBP-4 function reduces TGF-beta activation and enhances BMP-4
      signaling in the lung.
AB  - Disruption of latent TGF-beta binding protein (LTBP)-4 expression in the mouse
      leads to abnormal lung development and colorectal cancer. Lung fibroblasts from
      these mice produced decreased amounts of active TGF-beta, whereas secretion of
      latent TGF-beta was significantly increased. Expression and secretion of TGF
      beta2 and -beta3 increased considerably. These results suggested that TGF-beta
      activation but not secretion would be severely impaired in LTBP-4 -/-
      fibroblasts. Microarrays revealed increased expression of bone morphogenic
      protein (BMP)-4 and decreased expression of its inhibitor gremlin. This finding
      was accompanied by enhanced expression of BMP-4 target genes, inhibitors of
      differentiation 1 and 2, and increased deposition of fibronectin-rich
      extracellular matrix. Accordingly, increased expression of BMP-4 and decreased
      expression of gremlin were observed in mouse lung. Transfection of LTBP-4 rescued
      the -/- fibroblast phenotype, while LTBP-1 was inefficient. Treatment with active
      TGF-beta1 rescued BMP-4 and gremlin expression to wild-type levels. Our results
      indicate that the lack of LTBP-4-mediated targeting and activation of TGF-beta1
      leads to enhanced BMP-4 signaling in mouse lung.

PMID- 15466482
TI  - Sec1p directly stimulates SNARE-mediated membrane fusion in vitro.
AB  - Sec1 proteins are critical players in membrane trafficking, yet their precise
      role remains unknown. We have examined the role of Sec1p in the regulation of
      post-Golgi secretion in Saccharomyces cerevisiae. Indirect immunofluorescence
      shows that endogenous Sec1p is found primarily at the bud neck in newly budded
      cells and in patches broadly distributed within the plasma membrane in unbudded
      cells. Recombinant Sec1p binds strongly to the t-SNARE complex (Sso1p/Sec9c) as
      well as to the fully assembled ternary SNARE complex (Sso1p/Sec9c;Snc2p), but
      also binds weakly to free Sso1p. We used recombinant Sec1p to test Sec1p function
      using a well-characterized SNARE-mediated membrane fusion assay. The addition of
      Sec1p to a traditional in vitro fusion assay moderately stimulates fusion;
      however, when Sec1p is allowed to bind to SNAREs before reconstitution,
      significantly more Sec1p binding is detected and fusion is stimulated in a
      concentration-dependent manner. These data strongly argue that Sec1p directly
      stimulates SNARE-mediated membrane fusion.

PMID- 15466484
TI  - Epigenetics and cancer.
AB  - Epigenetic mechanisms act to change the accessibility of chromatin to
      transcriptional regulation locally and globally via modifications of the DNA and
      by modification or rearrangement of nucleosomes. Epigenetic gene regulation
      collaborates with genetic alterations in cancer development. This is evident from
      every aspect of tumor biology including cell growth and differentiation, cell
      cycle control, DNA repair, angiogenesis, migration, and evasion of host
      immunosurveillance. In contrast to genetic cancer causes, the possibility of
      reversing epigenetic codes may provide new targets for therapeutic intervention.

PMID- 15466483
TI  - XBP1: a link between the unfolded protein response, lipid biosynthesis, and
      biogenesis of the endoplasmic reticulum.
AB  - When the protein folding capacity of the endoplasmic reticulum (ER) is
      challenged, the unfolded protein response (UPR) maintains ER homeostasis by
      regulating protein synthesis and enhancing expression of resident ER proteins
      that facilitate protein maturation and degradation. Here, we report that enforced
      expression of XBP1(S), the active form of the XBP1 transcription factor generated
      by UPR-mediated splicing of XBP1 mRNA, is sufficient to induce synthesis of
      phosphatidylcholine, the primary phospholipid of the ER membrane. Cells
      overexpressing XBP1(S) exhibit elevated levels of membrane phospholipids,
      increased surface area and volume of rough ER, and enhanced activity of the
      cytidine diphosphocholine pathway of phosphatidylcholine biosynthesis. These data
      suggest that XBP1(S) links the mammalian UPR to phospholipid biosynthesis and ER
      biogenesis.

PMID- 15466485
TI  - The activity of the Nodal antagonist Cerl-2 in the mouse node is required for
      correct L/R body axis.
AB  - Correct establishment of the left/right (L/R) body asymmetry in the mouse embryo
      requires asymmetric activation of the evolutionarily conserved Nodal signaling
      cascade in the left lateral plate mesoderm (L-LPM). Furthermore, the presence of
      Nodal in the node is essential for its own expression in the L-LPM. Here, we have
      characterized the function of cerl-2, a novel Nodal antagonist, which displays a
      unique asymmetric expression on the right side of the mouse node. cerl-2 knockout
      mice display multiple laterality defects including randomization of the L/R axis.
      These defects can be partially rescued by removing one nodal allele. Our results
      demonstrate that Cerl-2 plays a key role in restricting the Nodal signaling
      pathway toward the left side of the mouse embryo by preventing its activity in
      the right side.

PMID- 15466486
TI  - A MyoD-generated feed-forward circuit temporally patterns gene expression during
      skeletal muscle differentiation.
AB  - The development and differentiation of distinct cell types is achieved through
      the sequential expression of subsets of genes; yet, the molecular mechanisms that
      temporally pattern gene expression remain largely unknown. In skeletal
      myogenesis, gene expression is initiated by MyoD and includes the expression of
      specific Mef2 isoforms and activation of the p38 mitogen-activated protein kinase
      (MAPK) pathway. Here, we show that p38 activity facilitates MyoD and Mef2 binding
      at a subset of late-activated promoters, and the binding of Mef2D recruits Pol
      II. Most importantly, expression of late-activated genes can be shifted to the
      early stages of differentiation by precocious activation of p38 and expression of
      Mef2D, demonstrating that a MyoD-mediated feed-forward circuit temporally
      patterns gene expression.

PMID- 15466487
TI  - Epidermal detachment, desmosomal dissociation, and destabilization of
      corneodesmosin in Spink5-/- mice.
AB  - Netherton syndrome (NS) is a human autosomal recessive skin disease caused by
      mutations in the SPINK5 gene, which encodes the putative proteinase inhibitor
      LEKTI. We have generated a transgenic mouse line with an insertional mutation
      that inactivated the mouse SPINK5 ortholog. Mutant mice exhibit fragile stratum
      corneum and perinatal death due to dehydration. Our analysis suggests that the
      phenotype is a consequence of desmosomal fragility associated with premature
      proteolysis of corneodesmosin, an extracellular desmosomal component. Our mouse
      mutant provides a model system for molecular studies of desmosomal stability and
      keratinocyte adhesion, and for designing therapeutic strategies to treat NS.

PMID- 15466488
TI  - SGS3 and SGS2/SDE1/RDR6 are required for juvenile development and the production
      of trans-acting siRNAs in Arabidopsis.
AB  - Higher plants undergo a transition from a juvenile to an adult phase of
      vegetative development prior to flowering. Screens for mutants that undergo this
      transition precociously produced alleles of two genes required for
      posttranscriptional gene silencing (PTGS)--SUPPRESSOR OF GENE SILENCING3 (SGS3)
      and SUPPRESSOR OF GENE SILENCING2(SGS2)/SILENCING DEFECTIVE1 (SDE1)/RNA-DEPENDENT
      POLYMERASE6 (RDR6). Loss-of-function mutations in these genes have a phenotype
      similar to that of mutations in the Argonaute gene ZIPPY (ZIP). Epistasis
      analysis suggests that ZIP, SGS3, SGS2/SDE1/RDR6, and the putative miRNA export
      receptor, HASTY (HST), operate in the same pathway(s). Microarray analysis
      revealed a small number of genes whose mRNA is increased in ZIP, SGS3, and
      SGS2/SDE1/RDR6 mutants, as well as genes that are up-regulated in SGS3 and
      SGS2/SDE1/RDR6 mutants, but not in ZIP mutants. One of these latter genes
      (At5g18040) is silenced posttranscriptionally in trans by the sRNA255 family of
      endogenous, noncoding, small interfering RNAs (siRNAs). The increase in At5g18040
      mRNA in SGS3 and SGS2/SDE1/RDR6 mutants is attributable to the absence of sRNA255
      like siRNAs in these mutants. These results demonstrate a role for endogenous
      siRNAs in the regulation of gene expression, and suggest that PTGS plays a
      central role in the temporal control of shoot development in plants.

PMID- 15466489
TI  - The small ubiquitin-like modifier (SUMO) is required for gonadal and uterine
      vulval morphogenesis in Caenorhabditis elegans.
AB  - The small ubiquitin-like modifier (SUMO) modification alters the subcellular
      distribution and function of its substrates. Here we show the major role of SUMO
      during the development of the Caenorhabditis elegans reproductive system. smo-1
      deletion mutants develop into sterile adults with abnormal somatic gonad, germ
      line, and vulva. SMO-1::GFP reporter is highly expressed in the somatic
      reproductive system. smo-1 animals lack a vulval-uterine connection as a result
      of impaired ventral uterine pi-cell differentiation and anchor cell fusion.
      Mutations in the LIN-11 LIM domain transcription factor lead to a uterine
      phenotype that resembles the smo-1 phenotype. LIN-11 is sumoylated, and its
      sumoylation is required for its activity during uterine morphogenesis. Expression
      of a SUMO-modified LIN-11 in the smo-1 background partially rescued pi-cell
      differentiation and retained LIN-11 in nuclear bodies. Thus, our results identify
      the reproductive system as the major SUMO target during postembryonic development
      and highlight LIN-11 as a physiological substrate whose sumoylation is associated
      with the formation of a functional vulval-uterine connection.

PMID- 15466490
TI  - Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation
      to hypertrophic differentiation of chondrocytes.
AB  - The Komeda miniature rat Ishikawa (KMI) is a naturally occurring mutant caused by
      an autosomal recessive mutation mri, which exhibits longitudinal growth
      retardation. Here we identified the mri mutation as a deletion in the rat gene
      encoding cGMP-dependent protein kinase type II (cGKII). KMIs showed an expanded
      growth plate and impaired bone healing with abnormal accumulation of postmitotic
      but nonhypertrophic chondrocytes. Ex vivo culture of KMI chondrocytes reproduced
      the differentiation impairment, which was restored by introducing the adenovirus
      mediated cGKII gene. The expression of Sox9, an inhibitory regulator of
      hypertrophic differentiation, persisted in the nuclei of postmitotic chondrocytes
      of the KMI growth plate. Transfection experiments in culture systems revealed
      that cGKII attenuated the Sox9 functions to induce the chondrogenic
      differentiation and to inhibit the hypertrophic differentiation of chondrocytes.
      This attenuation of Sox9 was due to the cGKII inhibition of nuclear entry of
      Sox9. The impaired differentiation of cultured KMI chondrocytes was restored by
      the silencing of Sox9 through RNA interference. Hence, the present study for the
      first time shed light on a novel role of cGKII as a molecular switch, coupling
      the cessation of proliferation and the start of hypertrophic differentiation of
      chondrocytes through attenuation of Sox9 function.

PMID- 15466491
TI  - Management of hepatitis C.
AB  - Hepatitis C virus (HCV) infection is a common cause of chronic liver disease and
      hepatocellular carcinoma. It is estimated that 15-20% of those infected will
      develop cirrhosis after 20 years of infection. It is transmitted parenterally,
      and HCV antibody and HCV RNA tests diagnose infection with a high degree of
      accuracy. Currently, a combination of peginterferon and ribavirin is the most
      efficacious treatment, with sustained viral response rates of 45% for genotype 1
      and 80% for genotypes 2 and 3. There is some evidence that treatment with
      interferon-based regimens can improve the natural history of this infection. The
      side effects of treatment are well recognized and include leucopenia,
      thrombocytopenia, haemolytic anaemia and depression. Patients with HCV-related
      decompensated cirrhosis and/or hepatocellular carcinoma should be considered for
      liver transplantation. The management of special groups, including those with
      acute HCV infection, co-infected with hepatitis B (HBV) or human immunodeficiency
      virus (HIV), continues to be defined.

PMID- 15466492
TI  - Bisphenol a glucuronidation and excretion in liver of pregnant and nonpregnant
      female rats.
AB  - In male rats challenged with the environmental estrogen bisphenol A, the compound
      is highly glucuronidated in the liver and is excreted largely into the bile.
      Given that in pregnancy the microsomal glucuronidation toward bisphenol A is
      attenuated, we hypothesized that elimination of bisphenol A from the liver may be
      reduced in pregnancy. This study was conducted to trace the elimination of
      bisphenol A in female rats, especially in pregnancy. In Sprague-Dawley rats, 1.5
      mumol of bisphenol A was perfused into the liver via the portal vein. In both the
      male and the nonpregnant female, the infused bisphenol A was glucuronidated, then
      the resultant glucuronide was excreted mainly into the bile. In pregnant rats,
      however, bilious excretion of bisphenol A glucuronide was 60% of that observed in
      nonpregnant rats, and venous excretion increased reciprocally. During 1-h
      perfusion, total excretion of the glucuronide from the liver of male, nonpregnant
      female, and pregnant rats was 889.5 +/- 69.6, 1256.7 +/- 54.8, and 1038.8 +/-
      33.3 nmoles, respectively. In Eisai hyperbilirubinemic rats (EHBR), perfusion of
      the liver with bisphenol A enabled us to determine that multidrug resistance
      associated protein (MRP)2-mediating transport is the mechanism behind excretion
      of the glucuronide into the bile. The expression of MRP2 has been reported to be
      noticeably reduced in pregnancy. These results suggest that bisphenol A
      elimination by hepatic glucuronidation is slightly less in pregnancy than in non
      pregnancy and that in pregnancy, more bisphenol A glucuronide is eliminated to
      the vein because of reduced MRP2 expression.

PMID- 15466493
TI  - Pharmacokinetics and metabolism of apigenin in female and male rats after a
      single oral administration.
AB  - The metabolism of apigenin, a weak estrogenic flavonoid phytochemical, was
      investigated in the rat. After a single oral administration of radiolabeled
      apigenin, 51.0% of radioactivity was recovered in urine, 12.0% in feces, 1.2% in
      the blood, 0.4% in the kidneys, 9.4% in the intestine, 1.2% in the liver, and
      24.8% in the rest of the body within 10 days. Sex differences appear with regard
      to the nature of compounds eliminated via the urinary route: immature male and
      female rats, like mature female rats, excreted a higher percentage of the mono
      glucuronoconjugate of apigenin than the mono-sulfoconjugate of apigenin (10.0
      31.6% versus 2.0-3.6%, respectively). Mature male rats excreted the same
      compounds in an inverse ratio (4.9% and 13.9%, respectively). Radioactivity
      appeared in the blood only 24 h after oral administration. Blood kinetics showed
      a high elimination half-time (91.8 h), a distribution volume of 259 ml, and a
      plasmatic clearance of 1.95 ml/h. All of the parameters calculated from these
      experiments suggested a slow metabolism of apigenin, with a slow absorption and a
      slow elimination phase. Thus, a possible accumulation of this flavonoid in the
      body can be hypothesized.

PMID- 15466494
TI  - Predicting super spreading events during the 2003 severe acute respiratory
      syndrome epidemics in Hong Kong and Singapore.
AB  - One of the intriguing characteristics of the 2003 severe acute respiratory
      syndrome (SARS) epidemics was the occurrence of super spreading events (SSEs).
      Here, the authors report the results of identifying the occurrence of SSEs in the
      Hong Kong and Singapore epidemics using mathematical and statistical analysis.
      Their predicted occurrence of SSEs agreed well with the reported occurrence of
      all seven super spreaders in the two cities. Additional unidentified SSEs were
      also found to exist. It was found that 71.1% and 74.8% of the infections were
      attributable to SSEs in Hong Kong and Singapore, respectively. There also seemed
      to be "synchronized" occurrences of infection peaks in both the community and the
      hospitals in Hong Kong. The results strongly suggested that the infection did not
      depend on the total number of symptomatic cases, with only a very small
      proportion of symptomatic individuals being shown to be infectious (i.e., able to
      infect other individuals). The authors found that the daily infection rate did
      not correlate with the daily total number of symptomatic cases but with the daily
      number of symptomatic cases who were not admitted to a hospital within 4 days of
      the onset of symptoms.

PMID- 15466495
TI  - CYP17 gene polymorphisms: prevalence and associations with hormone levels and
      related factors. a HuGE review.
AB  - The cytochrome P-450c17alpha (CYP17 ) gene, located on chromosome 10q24.3,
      encodes the enzyme cytochrome P-450c17alpha, which functions at key branch points
      in steroid hormone biosynthesis. Three polymorphisms have been described, but
      only the single base-pair change in the 5'-untranslated region (5'-UTR) has been
      investigated to any great extent. In single studies, the variant was associated
      with reduced messenger RNA level in ovarian cells but not with messenger RNA
      level in breast tissue. Homozygosity for the 5'-UTR variant is most common in
      East Asian (32%) and Japanese (22%) populations and is less common among White
      (mainly European and North American (14%)) and Black (mainly African-American
      (13%)) populations, but selection biases are likely to have affected these
      frequency estimates. Genotype appears to influence circulating estrogen levels in
      premenopausal women, while studies of relations with hormone levels in men have
      produced inconclusive results. However, relatively few studies have been
      conducted. Seven of 11 retrospective studies suggested a modest association
      between genotype and age at menarche. Random error in recall of age at menarche
      is likely to have attenuated this relation. Associations between genotype and
      postmenopausal estrogen use and bone mass have been observed in single studies.
      Further investigation of relations between genotype and hormone levels, exogenous
      hormone use, and markers of hormonal status may advance understanding of
      hormonally mediated diseases.

PMID- 15466496
TI  - Association of visceral adipose tissue with incident myocardial infarction in
      older men and women: the Health, Aging and Body Composition Study.
AB  - Assessment of body fat distribution, particularly visceral adipose tissue, may be
      important for accurate risk evaluation for cardiovascular disease in the elderly.
      This 1997-1998 US study examined the association of incident myocardial
      infarction (MI) with total adiposity (body mass index and fat mass) and body fat
      distribution (waist-to-thigh ratio, waist circumference, visceral and
      subcutaneous adipose tissue) in well-functioning men (n = 1,116) and women (n =
      1,387) aged 70-79 years enrolled in the Health, Aging and Body Composition Study.
      There were 116 MI events (71 in men, 45 in women) during an average follow-up
      time of 4.6 (standard deviation, 0.9) years. No association was found between
      incident MI and the adiposity or fat distribution variables for men. For women,
      visceral adipose tissue was an independent predictor of MI (hazard ratio = 1.67,
      95% confidence interval: 1.28, 2.17 per standard-deviation increase; p < 0.001).
      No association was found between body mass index or total fat mass and MI events
      in women. The association of visceral adipose tissue with MI in women was
      independent of high density lipoprotein cholesterol, interleukin-6 concentration,
      hypertension, and diabetes (hazard ratio = 1.79, 95% confidence interval: 1.24,
      2.58 per standard-deviation increase; p < 0.01). The amount of adipose tissue
      stored in the intraabdominal cavity is an important, independent risk factor for
      MI in well-functioning, elderly women.

PMID- 15466497
TI  - Insulin-like growth factor-1, insulin-like growth factor binding protein-3, and
      cardiovascular disease risk factors in young black men and white men: the CARDIA
      Male Hormone Study.
AB  - Cross-sectional studies have found associations between components of the insulin
      like growth factor (IGF) system and hypertension, total cholesterol, and low
      density lipoprotein cholesterol. Using partial correlation analysis and
      longitudinal analysis of data collected at the year 2, year 7, and year 10
      examinations, the authors assessed the associations of IGF-1 and IGF binding
      protein-3 (IGFBP-3) with cardiovascular disease risk factors in 544 Black and 747
      White male participants in the Coronary Artery Risk Development in Young Adults
      (CARDIA) Male Hormone Study who were aged 20-34 years at year 2 (1987-1988).
      There were no consistent independent associations with blood pressure. Cross
      sectionally, there were some inverse associations between IGF-1 and lipid levels
      in White men (strongest r = -0.095 (p = 0.02) for total cholesterol at year 7)
      and positive associations between IGFBP-3 and lipid levels in Black and White men
      (for log(triglycerides), r = 0.072-0.136). Longitudinally, a 1,000-ng/ml increase
      in IGFBP-3 was associated with 3.7-mg/dl and 2.6-mg/dl higher total cholesterol
      levels and 2.6-mg/dl and 1.7-mg/dl higher low density lipoprotein cholesterol
      levels in Black men and White men (p < 0.05), respectively. These findings do not
      support a strong link between IGF-1 and IGFBP-3 and blood pressure, but they do
      support the possibility of important relations between IGFBP-3 and lipid levels
      in young adult men.

PMID- 15466498
TI  - Work, leisure-time physical activity, and risk of preeclampsia and gestational
      hypertension.
AB  - Few studies of preeclampsia have assessed physical activity level, yet recent
      evidence suggests that the pathologic mechanisms in preeclampsia are similar to
      those in cardiovascular disease, for which physical activity is shown to be
      protective. The authors assessed the independent and combined effects of work and
      regular leisure-time physical activity (LTPA) during early pregnancy on risk of
      de novo preeclampsia (n = 44) and gestational hypertension (n = 172) among women
      recruited from 13 obstetric practices in the New Haven, Connecticut, area between
      1988 and 1991. Control subjects were normotensive throughout pregnancy (n =
      2,422). Information on time at work spent sitting, standing, and walking and on
      LTPA before and during pregnancy was collected via face-to-face interviews.
      Logistic regression analyses suggested that women who engaged in any regular LTPA
      regardless of caloric expenditure (adjusted odds ratio (aOR) = 0.66, 95%
      confidence interval (CI): 0.35, 1.22), were unemployed (aOR = 0.64, 95% CI: 0.21,
      2.00), or had nonsedentary jobs (aOR = 0.71, 95% CI: 0.37, 1.36) were at
      decreased risk of preeclampsia. Analyses of gestational hypertension showed no
      indication of a protective effect of workplace activity, LTPA, or unemployment.
      Consistent with other studies, these data suggest that regular physical activity
      during pregnancy may reduce preeclampsia risk.

PMID- 15466499
TI  - Menstrual and reproductive factors and risk of non-Hodgkin's lymphoma among
      Connecticut women.
AB  - Several recent studies have suggested a potential role of menstrual and
      reproductive factors in the risk of non-Hodgkin's lymphoma. To further examine
      the relation, the authors analyzed data from a population-based case-control
      study of non-Hodgkin's lymphoma in Connecticut women between 1996 and 2000. A
      total of 601 histologically confirmed cases and 717 randomly selected population
      based controls were included in this study. An in-person interview was conducted
      using a standardized and structured questionnaire to collect information on
      menstrual and reproductive factors and potential confounding factors. Compared
      with nulliparous women, women who had four or more pregnancies during their
      lifetime were found to have a significantly reduced risk of non-Hodgkin's
      lymphoma (odds ratio (OR) = 0.6, 95% confidence interval (CI): 0.4, 0.9). Risk
      appeared to decrease with increasing number of pregnancies (p(trend) = 0.03). The
      authors also observed an increased risk of non-Hodgkin's lymphoma overall (OR =
      1.5, 95% CI: 1.0, 2.2) and of diffuse non-Hodgkin's lymphoma (OR = 1.7, 95% CI:
      1.1, 2.7) for women who started their first menstrual period at age 15 or more
      years compared with those who started their first menstrual period before age 12
      years. These findings support a reduced risk of non-Hodgkin's lymphoma associated
      with multiple pregnancies and an increased risk of non-Hodgkin's lymphoma
      associated with later age at menarche.

PMID- 15466501
TI  - Incidence of laparoscopically confirmed endometriosis by demographic,
      anthropometric, and lifestyle factors.
AB  - The authors investigated the relations of demographic, anthropometric, and
      lifestyle factors with endometriosis in the Nurses' Health Study II prospective
      cohort. During 10 years of follow-up (1989-1999), 1,721 cases of laparoscopically
      confirmed endometriosis were reported among women with no past infertility. The
      incidence rate was greatest among women aged 25-29 years and lowest among women
      over 44 years (p(trend) < 0.0001). In multivariate Cox proportional hazards
      models, African-American women had a lower rate of disease compared with
      Caucasian women (rate ratio = 0.6, 95% confidence interval: 0.4, 0.9). The
      authors also observed an inverse relation with body mass index at age 18 years
      (for body mass index of >30 vs. 19-20.4 kg/m(2): rate ratio = 0.8, 95% confidence
      interval: 0.6, 1.1; p(trend) = 0.004) and with current alcohol intake (for >10
      vs. 0 g/day: rate ratio = 0.7, 95% confidence interval: 0.6, 0.8; p(trend) <
      0.0001) but no association with height, waist/hip ratio, or caffeine intake. An
      inverse relation with current body mass index and current cigarette smoking was
      observed only when cases were concurrently infertile. The authors conclude that
      age, race, body mass index, alcohol use, and cigarette smoking are associated
      with the incidence of endometriosis and that some of these relations may differ
      by infertility status at the time of laparoscopic diagnosis.

PMID- 15466500
TI  - Associations of seafood and elongated n-3 fatty acid intake with fetal growth and
      length of gestation: results from a US pregnancy cohort.
AB  - Previous studies, mainly among populations with high consumption of seafood, have
      suggested that increased marine n-3 polyunsaturated fatty acid (PUFA) intake
      during pregnancy promotes longer gestation and higher birth weight. Few studies
      have isolated the contribution of fetal growth to birth weight. Using data from
      2,109 pregnant women in Massachusetts enrolled in Project Viva from 1999 to 2002,
      the authors examined associations of marine n-3 PUFA and seafood intake with
      birth weight and birth-weight-for-gestational-age z value (fetal growth) using
      linear regression; length of gestation using median regression; and low birth
      weight, preterm delivery, and being small for gestational age using logistic
      regression. After adjustment for maternal and child factors, birth weight was 94
      (95% confidence interval: 23, 166) g lower and fetal growth z value 0.19 (95%
      confidence interval: 0.08, 0.31) units lower in the highest compared with the
      lowest quartile of first-trimester n-3 PUFA intake. Results for the second and
      third trimesters were similar, and findings for seafood paralleled those for n-3
      PUFA. Elongated n-3 PUFA intake and seafood intake were not associated with
      length of gestation or risk of preterm birth. Results from this US cohort support
      the conclusion that seafood intake during pregnancy is associated with reduced
      fetal growth.

PMID- 15466502
TI  - Validity of the Clock-Drawing Test as a screening tool for cognitive impairment
      in the elderly.
AB  - The authors studied the validity of the Clock-Drawing Test (CDT) in comparison
      with the Mini-Mental State Examination (MMSE) and the association between the CDT
      and mortality in a large general population sample of persons aged 75 years or
      more. Data were obtained from the MRC Trial of the Assessment and Management of
      Older People in the Community. Baseline assessments were conducted between 1995
      and 1999 in the United Kingdom. A total of 13,557 subjects with both CDT and MMSE
      scores were included in the analysis. The median follow-up period was 4.7 years.
      The sensitivity and specificity of the CDT for detecting moderate-to-severe
      cognitive impairment (MMSE score <or= 17) were 77% and 87%, respectively, for
      nurse administration and 40% and 91%, respectively, for postal administration.
      Sensitivity was higher among females and increased with age. In Cox proportional
      hazards regression, a worse CDT score was associated with increased risk of all
      cause mortality and mortality from cerebrovascular and respiratory diseases, even
      after adjustment for potential confounders. The authors conclude that the CDT may
      have value as a brief face-to-face screening tool for moderate/severe cognitive
      impairment in an older community population but is relatively poor at detecting
      milder cognitive impairment.

PMID- 15466503
TI  - Making a structured psychiatric diagnostic interview faithful to the
      nomenclature.
AB  - Psychiatric diagnostic interviews to be used in epidemiologic studies by lay
      interviewers have, since the 1970s, attempted to operationalize existing
      psychiatric nomenclatures. How to maximize the chances that they do so
      successfully has not previously been spelled out. In this article, the authors
      discuss strategies for each of the seven steps involved in writing, updating, or
      modifying a diagnostic interview and its supporting materials: 1) writing
      questions that match the nomenclature's criteria, 2) checking that respondents
      will be willing and able to answer the questions, 3) choosing a format acceptable
      to interviewers that maximizes accurate answering and recording of answers, 4)
      constructing a data entry and cleaning program that highlights errors to be
      corrected, 5) creating a diagnostic scoring program that matches the
      nomenclature's algorithms, 6) developing an interviewer training program that
      maximizes reliability, and 7) computerizing the interview. For each step, the
      authors discuss how to identify errors, correct them, and validate the revisions.
      Although operationalization will never be perfect because of ambiguities in the
      nomenclature, specifying methods for minimizing divergence from the nomenclature
      is timely as users modify existing interviews and look forward to updating
      interviews based on the Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition, and the International Classification of Diseases, Eleventh
      Revision.

PMID- 15466504
TI  - Within- and between-cohort variation in measured macronutrient intakes, taking
      account of measurement errors, in the European Prospective Investigation into
      Cancer and Nutrition study.
AB  - Multicenter epidemiologic studies provide a unique opportunity to evaluate the
      association between exposure and disease at the individual and the aggregate
      levels. The two components can eventually be pooled to corroborate each other,
      using weights proportional to the intraclass correlation coefficient (ICC), which
      expresses the amount of between-cohort variability in the exposure variable
      compared with the total. The greater the ICC, the more the overall estimate will
      reflect the between-cohort component. Dietary measurements are affected by
      measurement errors, particularly within a cohort. In 1992-2000, the variability
      of macronutrient intake distribution before and after calibration for measurement
      error in the European Prospective Investigation into Cancer and Nutrition was
      evaluated. A two-level, random-effects model was used. Evaluation of
      macronutrient densities revealed that energy has a considerable effect on the
      calibration model, leading to ICC values larger than those for the absolute
      intakes. Given the shrinkage of the within-center variability, a sizable increase
      in the ICC was observed for protein in men and women (0.48 and 0.54,
      respectively) and carbohydrates in men (0.41). Results suggest that the effect of
      calibration on macronutrient intake variability is greater for the within-cohort
      component, thus increasing the relative importance of the between-cohort
      component. After calibration, the two components had a similar weight. This
      observation has important implications for the analysis of multicenter studies
      because the between-cohort component provides a large part of the overall
      heterogeneity.

PMID- 15466505
TI  - Re: "Mesothelioma trends in the United States: an update based on surveillance,
      epidemiology, and end results program data for 1973 through 2003".

PMID- 15466506
TI  - Lactic acid bacteria as a potential source of enzymes for use in vinification.

PMID- 15466507
TI  - Use of semiconductor quantum dots for photostable immunofluorescence labeling of
      Cryptosporidium parvum.
AB  - Cryptosporidium parvum is a waterborne pathogen that poses potential risk to
      drinking water consumers. The detection of Cryptosporidium oocysts, its
      transmissive stage, is used in the latest U.S. Environmental Protection Agency
      method 1622, which utilizes organic fluorophores such as fluorescein
      isothiocyanate (FITC) to label the oocysts by conjugation with anti
      Cryptosporidium sp. monoclonal antibody (MAb). However, FITC exhibits low
      resistance to photodegradation. This property will inevitably limit the detection
      accuracy after a short period of continuous illumination. In view of this, the
      use of inorganic fluorophores, such as quantum dot (QD), which has a high
      photobleaching threshold, in place of the organic fluorophores could potentially
      enhance oocyst detection. In this study, QD605-streptavidin together with
      biotinylated MAb was used for C. parvum oocyst detection. The C. parvum oocyst
      detection sensitivity increased when the QD605-streptavidin concentration was
      increased from 5 to 15 nM and eventually leveled off at a saturation
      concentration of 20 nM and above. The minimum QD605-streptavidin saturation
      concentration for detecting up to 4,495 +/- 501 oocysts (mean +/- standard
      deviation) was determined to be 20 nM. The difference in the enumeration between
      20 nM QD605-streptavidin with biotinylated MAb and FITC-MAb was insignificant (P
      > 0.126) when various C. parvum oocyst concentrations were used. The QD605 was
      highly photostable while the FITC intensity decreased to 19.5% +/- 5.6% of its
      initial intensity after 5 min of continuous illumination. The QD605-based
      technique was also shown to be sensitive for oocyst detection in reservoir water.
      This observation showed that the QD method developed in this study was able to
      provide a sensitive technique for detecting C. parvum oocysts with the advantage
      of having a high photobleaching threshold.

PMID- 15466508
TI  - Distribution of Escherichia coli O157 in bovine fecal pats and its impact on
      estimates of the prevalence of fecal shedding.
AB  - The distribution of Escherichia coli O157 in bovine feces was examined by testing
      multiple samples from fecal pats and determining the density of E. coli O157 in
      immunomagnetic separation (IMS)-positive fecal samples. The density of E. coli
      O157 in bovine feces was highly variable, differing by as much as 76,800 CFU g(
      1) between samples from the same fecal pat. The density in most positive samples
      was <100 CFU g(-1), the limit of reliable detection by IMS. Testing only one 1-g
      sample of feces per pat with IMS may result in a sensitivity of detection as low
      as 20 to 50%. It is therefore probable that most surveys have greatly
      underestimated the prevalence of E. coli O157 shedding in cattle and the
      proportion of farms with shedding cattle. The sensitivity of the detection of E.
      coli O157 in bovine feces can be as much as doubled by testing two 1-g samples
      per pat rather than one 1-g sample.

PMID- 15466509
TI  - Ferrihydrite-dependent growth of Sulfurospirillum deleyianum through electron
      transfer via sulfur cycling.
AB  - Observations in enrichment cultures of ferric iron-reducing bacteria indicated
      that ferrihydrite was reduced to ferrous iron minerals via sulfur cycling with
      sulfide as the reductant. Ferric iron reduction via sulfur cycling was
      investigated in more detail with Sulfurospirillum deleyianum, which can utilize
      sulfur or thiosulfate as an electron acceptor. In the presence of cysteine (0.5
      or 2 mM) as the sole sulfur source, no (microbial) reduction of ferrihydrite or
      ferric citrate was observed, indicating that S. deleyianum is unable to use
      ferric iron as an immediate electron acceptor. However, with thiosulfate at a low
      concentration (0.05 mM), growth with ferrihydrite (6 mM) was possible and sulfur
      was cycled up to 60 times. Also, spatially distant ferrihydrite in agar cultures
      was reduced via diffusible sulfur species. Due to the low concentrations of
      thiosulfate, S. deleyianum produced only small amounts of sulfide. Obviously,
      sulfide delivered electrons to ferrihydrite with no or only little precipitation
      of black iron sulfides. Ferrous iron and oxidized sulfur species were produced
      instead, and the latter served again as the electron acceptor. These oxidized
      sulfur species have not yet been identified. However, sulfate and sulfite cannot
      be major products of ferrihydrite-dependent sulfide oxidation, since neither
      compound can serve as an electron acceptor for S. deleyianum. Instead, sulfur
      (elemental S or polysulfides) and/or thiosulfate as oxidized products could
      complete a sulfur cycle-mediated reduction of ferrihydrite.

PMID- 15466510
TI  - Mechanisms of bactericidal action of cinnamaldehyde against Listeria
      monocytogenes and of eugenol against L. monocytogenes and Lactobacillus sakei.
AB  - The spice oil components eugenol and cinnamaldehyde possess activity against both
      gram-positive and gram-negative bacteria, but the mechanisms of action remain
      obscure. In broth media at 20 degrees C, 5 mM eugenol or 30 mM cinnamaldehyde was
      bactericidal (>1-log reduction in the number of CFU per milliliter in 1 h) to
      Listeria monocytogenes. At a concentration of 6 mM eugenol was bactericidal to
      Lactobacillus sakei, but treatment with 0.5 M cinnamaldehyde had no significant
      effect. To investigate the role of interference with energy generation in the
      mechanism of action, the cellular and extracellular ATP levels of cells in HEPES
      buffer at 20 degrees C were measured. Treatment of nonenergized L. monocytogenes
      with 5 mM eugenol, 40 mM cinnamaldehyde, or 10 microM carbonyl cyanide m
      chlorophenylhydrazone (CCCP) for 5 min prevented an increase in the cellular ATP
      concentration upon addition of glucose. Treatment of energized L. monocytogenes
      with 40 mM cinnamaldehyde or 10 microM CCCP caused a rapid decline in cellular
      ATP levels, but 5 mM eugenol had no effect on cellular ATP. Treatment of L. sakei
      with 10 mM eugenol prevented ATP generation by nonenergized cells and had no
      effect on the cellular ATP of energized cells. CCCP at a concentration of 100
      microM had no significant effect on the cellular ATP of L. sakei. No significant
      changes in extracellular ATP were observed. Due to their rapidity, effects on
      energy generation clearly play a major role in the activity of eugenol and
      cinnamaldehyde at bactericidal concentrations. The possible mechanisms of
      inhibition of energy generation are inhibition of glucose uptake or utilization
      of glucose and effects on membrane permeability.

PMID- 15466511
TI  - Discovery of rare and highly toxic microcystins from lichen-associated
      cyanobacterium Nostoc sp. strain IO-102-I.
AB  - The production of hepatotoxic cyclic heptapeptides, microcystins, is almost
      exclusively reported from planktonic cyanobacteria. Here we show that a
      terrestrial cyanobacterium Nostoc sp. strain IO-102-I isolated from a lichen
      association produces six different microcystins. Microcystins were identified
      with liquid chromatography-UV mass spectrometry by their retention times, UV
      spectra, mass fragmentation, and comparison to microcystins from the aquatic
      Nostoc sp. strain 152. The dominant microcystin produced by Nostoc sp. strain IO
      102-I was the highly toxic [ADMAdda(5)]microcystin-LR, which accounted for ca.
      80% of the total microcystins. We assigned a structure of [DMAdda(5)]microcystin
      LR and [d-Asp(3),ADMAdda(5)]microcystin-LR and a partial structure of three new
      [ADMAdda(5)]-XR type of microcystin variants. Interestingly, Nostoc spp. strains
      IO-102-I and 152 synthesized only the rare ADMAdda and DMAdda subfamilies of
      microcystin variants. Phylogenetic analyses demonstrated congruence between genes
      involved directly in microcystin biosynthesis and the 16S rRNA and rpoC1 genes of
      Nostoc sp. strain IO-102-I. Nostoc sp. strain 152 and the Nostoc sp. strain IO
      102-I are distantly related, revealing a sporadic distribution of toxin
      production in the genus Nostoc. Nostoc sp. strain IO-102-I is closely related to
      Nostoc punctiforme PCC 73102 and other symbiotic Nostoc strains and most likely
      belongs to this species. Together, this suggests that other terrestrial and
      aquatic strains of the genus Nostoc may have retained the genes necessary for
      microcystin biosynthesis.

PMID- 15466512
TI  - Persistence of vancomycin-resistant enterococci in New Zealand broilers after
      discontinuation of avoparcin use.
AB  - Large amounts of tylosin, zinc-bacitracin, and avilamycin are currently used as
      prophylactics in New Zealand broiler production. Avoparcin was also used from
      1977 to 2000. A total of 382 enterococci were isolated from 213 fecal samples
      (147 individual poultry farms) using enrichment broths plated on m-Enterococcus
      agar lacking antimicrobials. These isolates were then examined to determine the
      prevalence of antimicrobial resistance. Of the 382 isolates, 5.8% (22 isolates)
      were resistant to vancomycin, and 64.7% were resistant to erythromycin. The
      bacitracin MIC was > or =256 microg/ml for 98.7% of isolates, and the avilamycin
      MIC was > or =8 microg/ml for 14.9% of isolates. No resistance to ampicillin or
      gentamicin was detected. Of the 22 vancomycin-resistant enterococci (VRE)
      isolates, 18 (81.8%) were Enterococcus faecalis, 3 were Enterococcus faecium, and
      1 was Enterococcus durans. However, when the 213 fecal enrichment broths were
      plated on m-Enterococcus agar containing vancomycin, 86 VRE were recovered; 66%
      of these isolates were E. faecium and the remainder were E. faecalis. Vancomycin
      resistant E. faecium isolates were found to have heterogenous pulsed-field gel
      electrophoresis (PFGE) patterns of SmaI-digested DNA, whereas the PFGE patterns
      of vancomycin-resistant E. faecalis isolates were identical or closely related,
      suggesting that this VRE clone is widespread throughout New Zealand. These data
      demonstrate that vancomycin-resistant E. faecalis persists in the absence and
      presence of vancomycin-selective pressure, thus explaining the dominance of this
      VRE clone even in the absence of avoparcin.

PMID- 15466513
TI  - Riboflavin production in Lactococcus lactis: potential for in situ production of
      vitamin-enriched foods.
AB  - This study describes the genetic analysis of the riboflavin (vitamin B(2))
      biosynthetic (rib) operon in the lactic acid bacterium Lactococcus lactis subsp.
      cremoris strain NZ9000. Functional analysis of the genes of the L. lactis rib
      operon was performed by using complementation studies, as well as by deletion
      analysis. In addition, gene-specific genetic engineering was used to examine
      which genes of the rib operon need to be overexpressed in order to effect
      riboflavin overproduction. Transcriptional regulation of the L. lactis riboflavin
      biosynthetic process was investigated by using Northern hybridization and primer
      extension, as well as the analysis of roseoflavin-induced riboflavin
      overproducing L. lactis isolates. The latter analysis revealed the presence of
      both nucleotide replacements and deletions in the regulatory region of the rib
      operon. The results presented here are an important step toward the development
      of fermented foods containing increased levels of riboflavin, produced in situ,
      thus negating the need for vitamin fortification.

PMID- 15466515
TI  - Strain-specific differences in the grazing sensitivities of closely related
      ultramicrobacteria affiliated with the Polynucleobacter cluster.
AB  - Ultramicrobacteria (cell volume < 0.1 microm(3)) are the numerically dominant
      organisms in the plankton of marine and freshwater habitats. Flagellates and
      other protists are assumed to be the most important predators of these
      ultramicrobacteria as well as of larger planktonic bacteria. However, due to
      controversial observations conducted previously, it is not clear as to whether
      fractions of the ultramicrobacteria are resistant to flagellate predation.
      Furthermore, it is not known if closely related bacteria vary significantly in
      their sensitivity to flagellate predation. We investigated the sensitivity of
      ultramicrobacteria affiliated with the cosmopolitan Polynucleobacter cluster to
      grazing by Spumella-like nanoflagellates. Laboratory grazing experiments with
      four closely related (> or =99.6% 16S rRNA gene sequence similarity) bacteria and
      three closely related (100% 18S rRNA gene sequence similarity) flagellates were
      performed. In comparison to larger bacteria, predation on the ultramicrobacterial
      Polynucleobacter strains was weak, and the growth of the predating flagellates
      was slow. Specific clearance rates ranged between 0.14 x 10(5) and 2.8 x 10(5)
      units of predator size h(-1). Feeding rates strongly depended on the flagellate
      and bacterial strain (P < 0.001). Grazing mortality rates of the three flagellate
      strains investigated varied for the same prey strain by up to almost fourfold. We
      conclude that (i) ultramicrobacteria affiliated with the Polynucleobacter cluster
      are not protected from grazing, (ii) strain-specific variations in grazing
      sensitivity even between closely related bacteria are high, and (iii) strain
      specific differences in predator-prey interaction could be an important factor in
      the evolution and maintenance of microbial microdiversity.

PMID- 15466514
TI  - Stable-isotope probing of microorganisms thriving at thermodynamic limits:
      syntrophic propionate oxidation in flooded soil.
AB  - Propionate is an important intermediate of the degradation of organic matter in
      many anoxic environments. In methanogenic environments, due to thermodynamic
      constraints, the oxidation of propionate requires syntrophic cooperation of
      propionate-fermenting proton-reducing bacteria and H(2)-consuming methanogens. We
      have identified here microorganisms that were active in syntrophic propionate
      oxidation in anoxic paddy soil by rRNA-based stable-isotope probing (SIP). After
      7 weeks of incubation with [(13)C]propionate (<10 mM) and the oxidation of
      approximately 30 micromol of (13)C-labeled substrate per g dry weight of soil, we
      found that archaeal nucleic acids were (13)C labeled to a larger extent than
      those of the bacterial partners. Nevertheless, both terminal restriction fragment
      length polymorphism and cloning analyses revealed Syntrophobacter spp., Smithella
      spp., and the novel Pelotomaculum spp. to predominate in "heavy" (13)C-labeled
      bacterial rRNA, clearly showing that these were active in situ in syntrophic
      propionate oxidation. Among the Archaea, mostly Methanobacterium and
      Methanosarcina spp. and also members of the yet-uncultured "rice cluster I"
      lineage had incorporated substantial amounts of (13)C label, suggesting that
      these methanogens were directly involved in syntrophic associations and/or
      thriving on the [(13)C]acetate released by the syntrophs. With this first
      application of SIP in an anoxic soil environment, we were able to clearly
      demonstrate that even guilds of microorganisms growing under thermodynamic
      constraints, as well as phylogenetically diverse syntrophic associations, can be
      identified by using SIP. This approach holds great promise for determining the
      structure and function relationships of further syntrophic or other nutritional
      associations in natural environments and for defining metabolic functions of yet
      uncultivated microorganisms.

PMID- 15466516
TI  - Isolation and purification of pyranose 2-oxidase from Phanerochaete chrysosporium
      and characterization of gene structure and regulation.
AB  - Pyranose 2-oxidase (POX) was recovered from Phanerochaete chrysosporium BKM-F
      1767 solid substrate culture using mild extraction conditions and was purified.
      (13)C-nuclear magnetic resonance confirmed production of d-arabino-hexos-2-ulose
      (glucosone) from d-glucose with the oxidase. Peptide fingerprints generated by
      liquid chromatography-tandem mass spectrometry of tryptic digests and analysis of
      the corresponding cDNA revealed a structurally unusual sequence for the P.
      chrysosporium POX. Relatively high levels of pox transcript were detected under
      carbon-starved culture conditions but not under nutrient sufficiency. This
      regulation pattern is similar to that observed for lignin peroxidases, manganese
      peroxidases, and glyoxal oxidase of P. chrysosporium, supporting evidence that
      POX has a role in lignocellulose degradation.

PMID- 15466517
TI  - Development and application of a selective PCR-denaturing gradient gel
      electrophoresis approach to detect a recently cultivated Bacillus group
      predominant in soil.
AB  - The worldwide presence of a hitherto-nondescribed group of predominant soil
      microorganisms related to Bacillus benzoevorans was analyzed after development of
      two sets of selective primers targeting 16S rRNA genes in combination with
      denaturing gradient gel electrophoresis (DGGE). The high abundance and
      cultivability of at least some of these microorganisms makes them an appropriate
      subject for studies on their biogeographical dissemination and diversity. Since
      cultivability can vary significantly with the physiological state and even
      between closely related strains, we developed a culture-independent 16S rRNA gene
      targeted DGGE fingerprinting protocol for the detection of these bacteria from
      soil samples. The composition of the B. benzoevorans relatives in the soil
      samples from The Netherlands, Bulgaria, Russia, Pakistan, and Portugal showed
      remarkable differences between the different countries. Differences in the DGGE
      profiles of these communities in archived soil samples from the Dutch
      Wieringermeer polder were observed over time during which a shift from anaerobic
      to aerobic and from saline to freshwater conditions occurred. To complement the
      molecular methods, we additionally cultivated B. benzoevorans-related strains
      from all of the soil samples. The highest number of B. benzoevorans relatives was
      found in the soils from the northern part of The Netherlands. The present study
      contributes to our knowledge of the diversity and abundance of this interesting
      group of microbes in soils throughout the world.

PMID- 15466518
TI  - Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a
      major fermentation product.
AB  - The microbial community of the human colon contains many bacteria that produce
      lactic acid, but lactate is normally detected only at low concentrations (<5 mM)
      in feces from healthy individuals. It is not clear, however, which bacteria are
      mainly responsible for lactate utilization in the human colon. Here, bacteria
      able to utilize lactate and produce butyrate were identified among isolates
      obtained from 10(-8) dilutions of fecal samples from five different subjects. Out
      of nine such strains identified, four were found to be related to Eubacterium
      hallii and two to Anaerostipes caccae, while the remaining three represent a new
      species within clostridial cluster XIVa based on their 16S rRNA sequences.
      Significant ability to utilize lactate was not detected in the butyrate-producing
      species Roseburia intestinalis, Eubacterium rectale, or Faecalibacterium
      prausnitzii. Whereas E. hallii and A. caccae strains used both D- and L-lactate,
      the remaining strains used only the d form. Addition of glucose to batch cultures
      prevented lactate utilization until the glucose became exhausted. However, when
      two E. hallii strains and one A. caccae strain were grown in separate cocultures
      with a starch-utilizing Bifidobacterium adolescentis isolate, with starch as the
      carbohydrate energy source, the L-lactate produced by B. adolescentis became
      undetectable and butyrate was formed. Such cross-feeding may help to explain the
      reported butyrogenic effect of certain dietary substrates, including resistant
      starch. The abundance of E. hallii in particular in the colonic ecosystem
      suggests that these bacteria play important roles in preventing lactate
      accumulation.

PMID- 15466519
TI  - Identification of the receptor-binding protein in 936-species lactococcal
      bacteriophages.
AB  - The aim of this work was to identify genes responsible for host recognition in
      the lactococcal phages sk1 and bIL170 belonging to species 936. These phages have
      a high level of DNA identity but different host ranges. Bioinformatic analysis
      indicated that homologous genes, orf18 in sk1 and orf20 in bIL170, could be the
      receptor-binding protein (RBP) genes, since the resulting proteins were unrelated
      in the C-terminal part and showed homology to different groups of proteins
      hypothetically involved in host recognition. Consequently, chimeric bIL170 phages
      carrying orf18 from sk1 were generated. The recombinant phages were able to form
      plaques on the sk1 host Lactococcus lactis MG1614, and recombination was verified
      by PCR analysis directly with the plaques. A polyclonal antiserum raised against
      the C-terminal part of phage sk1 ORF18 was used in immunogold electron microscopy
      to demonstrate that ORF18 is located at the tip of the tail. Sequence analysis of
      corresponding proteins from other lactococcal phages belonging to species 936
      showed that the N-terminal parts of the RBPs were very similar, while the C
      terminal parts varied, suggesting that the C-terminal part plays a role in
      receptor binding. The phages investigated could be grouped into sk1-like phages
      (p2, fd13, jj50, and phi 7) and bIL170-like phages (P008, P113G, P272, and bIL66)
      on the basis of the homology of their RBPs to the C-terminal part of ORF18 in sk1
      and ORF20 in bIL170, respectively. Interestingly, sk1-like phages bind to and
      infect a defined group of L. lactis subsp. cremoris strains, while bIL170-like
      phages bind to and infect a defined group of L. lactis subsp. lactis strains.

PMID- 15466520
TI  - Identification of Lactococcus lactis genes required for bacteriophage adsorption.
AB  - The aim of this work was to identify genes in Lactococcus lactis subsp. lactis
      IL1403 and Lactococcus lactis subsp. cremoris Wg2 important for adsorption of the
      936-species phages bIL170 and phi 645, respectively. Random insertional
      mutagenesis of the two L. lactis strains was carried out with the vector
      pGh9:ISS1, and integrants that were resistant to phage infection and showed
      reduced phage adsorption were selected. In L. lactis IL1403 integration was
      obtained in the ycaG and rgpE genes, whereas in L. lactis Wg2 integration was
      obtained in two genes homologous to ycbC and ycbB of L. lactis IL1403. rgpE and
      ycbB encode putative glycosyltransferases, whereas ycaG and ycbC encode putative
      membrane-spanning proteins with unknown functions. Interestingly, ycaG, rgpE,
      ycbC, and ycbB are all part of the same operon in L. lactis IL1403. This operon
      is probably involved in biosynthesis and transport of cell wall polysaccharides
      (WPS). Binding and infection studies showed that phi645 binds to and infects L.
      lactis Wg2, L. lactis IL1403, and L. lactis IL1403 strains with pGh9:ISS1
      integration in ycaG and rgpE, whereas bIL170 binds to and infects only L. lactis
      IL1403 and cannot infect Wg2. These results indicate that phi 645 binds to a WPS
      structure present in both L. lactis IL1403 and L. lactis Wg2, whereas bIL170
      binds to another WPS structure not present in L. lactis Wg2. Binding of bIL170
      and phi 645 to different WPS structures was supported by alignment of the
      receptor-binding proteins of bIL170 and phi 645 that showed no homology in the C
      terminal part.

PMID- 15466521
TI  - Listeria monocytogenes isolates from foods and humans form distinct but
      overlapping populations.
AB  - A total of 502 Listeria monocytogenes isolates from food and 492 from humans were
      subtyped by EcoRI ribotyping and PCR-restriction fragment length polymorphism
      analysis of the virulence gene hly. Isolates were further classified into genetic
      lineages based on subtyping results. Food isolates were obtained through a survey
      of selected ready-to-eat food products in Maryland and California in 2000 and
      2001. Human isolates comprised 42 isolates from invasive listeriosis cases
      reported in Maryland and California during 2000 and 2001 as well as an additional
      450 isolates from cases that had occurred throughout the United States,
      predominantly from 1997 to 2001. Assignment of isolates to lineages and to the
      majority of L. monocytogenes subtypes was significantly associated with the
      isolate source (food or human), although most subtypes and lineages included both
      human and food isolates. Some subtypes were also significantly associated with
      isolation from specific food types. Tissue culture plaque assay characterization
      of the 42 human isolates from Maryland and California and of 91 representative
      food isolates revealed significantly higher average infectivity and cell-to-cell
      spread for the human isolates, further supporting the hypothesis that food and
      human isolates form distinct populations. Combined analysis of subtype and
      cytopathogenicity data showed that strains classified into specific ribotypes
      previously linked to multiple human listeriosis outbreaks, as well as those
      classified into lineage I, are more common among human cases and generate larger
      plaques than other subtypes, suggesting that these subtypes may represent
      particularly virulent clonal groups. These data will provide a framework for
      prediction of the public health risk associated with specific L. monocytogenes
      subtypes.

PMID- 15466522
TI  - Movement of viruses between biomes.
AB  - Viruses are abundant in all known ecosystems. In the present study, we tested the
      possibility that viruses from one biome can successfully propagate in another.
      Viral concentrates were prepared from different near-shore marine sites, lake
      water, marine sediments, and soil. The concentrates were added to microcosms
      containing dissolved organic matter as a food source (after filtration to allow
      100-kDa particles to pass through) and a 3% (vol/vol) microbial inoculum from a
      marine water sample (after filtration through a 0.45-microm-pore-size filter).
      Virus-like particle abundances were then monitored using direct counting. Viral
      populations from lake water, marine sediments, and soil were able to replicate
      when they were incubated with the marine microbes, showing that viruses can move
      between different ecosystems and propagate. These results imply that viruses can
      laterally transfer DNA between microbes in different biomes.

PMID- 15466523
TI  - Statistical quantification of detachment rates and size distributions of cell
      clumps from wild-type (PAO1) and cell signaling mutant (JP1) Pseudomonas
      aeruginosa biofilms.
AB  - The detachment of cells from bacterial biofilms is an important, yet poorly
      understood and largely unquantified phenomenon. Detached cell clumps from medical
      devices may form microemboli and lead to metastasis, especially if they are
      resistant to host defenses and antibiotics. In manufacturing plants detached
      clumps entering a process stream decrease product quality. Two strains of
      Pseudomonas aeruginosa, a wild type (PAO1) and a cell signaling mutant (JP1),
      were studied to (i) quantify and model detachment patterns and (ii) determine the
      influence of cell signaling on detachment. We collected effluent from a biofilm
      flowthrough reactor and determined the size distribution for cell detachment
      events by microscopic examination and image analysis. The two strains were
      similar in terms of both biofilm structure and detachment patterns. Most of the
      detachment events were single-cell events; however, multiple-cell detachment
      events contributed a large fraction of the total detached cells. The rates at
      which events containing multiple cells detached from the biofilm were estimated
      by fitting a statistical model to the size distribution data. For events
      consisting of at least 1,000 cells, the estimated rates were 4.5 events mm(-2)
      min(-1) for PAO1 and 4.3 events mm(-2) min(-1) for JP1. These rates may be
      significant when they are scaled up to the total area of a real biofilm
      contaminated medical device surface and to the hours or days of patient exposure.

PMID- 15466524
TI  - Characterization of plasmid pOR1 from Ornithobacterium rhinotracheale and
      construction of a shuttle plasmid.
AB  - The bacterium Ornithobacterium rhinotracheale has been recognized as an emerging
      pathogen in poultry since about 10 years ago. Knowledge of this bacterium and its
      mechanisms of virulence is still very limited. Here we report the development of
      a transformation system that enables genetic modification of O. rhinotracheale.
      The system is based on a cryptic plasmid, pOR1, that was derived from an O.
      rhinotracheale strain of serotype K. Sequencing indicated that the plasmid
      consisted of 14,787 nucleotides. Sequence analysis revealed one replication
      origin and several rep genes that control plasmid replication and copy number,
      respectively. In addition, pOR1 contains genes with similarity to a heavy-metal
      transporting ATPase, a TonB-linked siderophore receptor, and a laccase. Reverse
      transcription-PCR demonstrated that these genes were transcribed. Other putative
      open reading frames exhibited similarities with a virulence-associated protein in
      Actinobacillus actinomycetemcomitans and a number of genes coding for proteins
      with unknown function. An Escherichia coli-O. rhinotracheale shuttle plasmid
      (pOREC1) was constructed by cloning the replication origin and rep genes from
      pOR1 and the cfxA gene from Bacteroides vulgatus, which codes for resistance to
      the antibiotic cefoxitin, into plasmid pGEM7 by using E. coli as a host. pOREC1
      was electroporated into O. rhinotracheale and yielded cefoxitin-resistant
      transformants. The pOREC1 isolated from these transformants was reintroduced into
      E. coli, demonstrating that pOREC1 acts as an independent replicon in both E.
      coli and O. rhinotracheale, fulfilling the criteria for a shuttle plasmid that
      can be used for transformation, targeted mutagenesis, and the construction of
      defined attenuated vaccine strains.

PMID- 15466525
TI  - Inheritance of resistance to Bacillus thuringiensis subsp. kurstaki in
      Trichoplusia ni.
AB  - The genetic inheritance of resistance to a commercial formulation of Bacillus
      thuringiensis subsp. kurstaki was examined in a Trichoplusia ni colony initiated
      from a resistant population present in a commercial vegetable greenhouse in
      British Columbia, Canada. Progeny of F(1) reciprocal crosses and backcrosses
      between F(1) larvae and resistant (P(R)) and susceptible (P(S)) populations were
      assayed at different B. thuringiensis subsp. kurstaki concentrations. The
      responses of progeny of reciprocal F(1) crosses were identical, indicating that
      the resistant trait was autosomal. The 50% lethal concentration for the F(1)
      larvae was slightly higher than that for P(S), suggesting that resistance is
      partially recessive. The responses of both backcross progeny (F(1) x P(R), F(1) x
      P(S)) did not correspond to predictions from a single-locus model. The inclusion
      of a nonhomozygous resistant parental line in the monogenic model significantly
      increased the correspondence between the expected and observed results for the
      F(1) x P(R) backcross but decreased the correspondence with the F(1) x P(S)
      backcross results. This finding suggests that resistance to B. thuringiensis
      subsp. kurstaki in this T. ni population is due to more than one gene.

PMID- 15466526
TI  - Bacterial community structure and diversity in a century-old manure-treated
      agroecosystem.
AB  - Changes in soil microbial community structure and diversity may reflect
      environmental impact. We examined 16S rRNA gene fingerprints of bacterial
      communities in six agroecosystems by PCR amplification and denaturing gradient
      gel electrophoresis (PCR-DGGE) separation. These soils were treated with manure
      for over a century or different fertilizers for over 70 years. Bacterial
      community structure and diversity were affected by soil management practices, as
      evidenced by changes in the PCR-DGGE banding patterns. Bacterial community
      structure in the manure-treated soil was more closely related to the structure in
      the untreated soil than that in soils treated with inorganic fertilizers. Lime
      treatment had little effect on bacterial community structure. Soils treated with
      P and N-P had bacterial community structures more closely related to each other
      than to those of soils given other treatments. Among the soils tested, a
      significantly higher number of bacterial ribotypes and a more even distribution
      of the bacterial community existed in the manure-treated soil. Of the 99 clones
      obtained from the soil treated with manure for over a century, two (both
      Pseudomonas spp.) exhibited 100% similarity to sequences in the GenBank database.
      Two of the clones were possible chimeras. Based on similarity matching, the
      remaining 97 clones formed six major clusters. Fifty-six out of 97 were assigned
      taxonomic units which grouped into five major taxa: alpha-, beta-, and gamma
      Proteobacteria (36 clones), Acidobacteria (16 clones), Bacteroidetes (2 clones),
      Nitrospirae (1 clone), and Firmicutes (1 clone). Forty-one clones remained
      unclassified. Results from this study suggested that bacterial community
      structure was closely related to agroecosystem management practices conducted for
      over 70 years.

PMID- 15466527
TI  - Chthoniobacter flavus gen. nov., sp. nov., the first pure-culture representative
      of subdivision two, Spartobacteria classis nov., of the phylum Verrucomicrobia.
AB  - The phylum Verrucomicrobia is increasingly recognized as an environmentally
      significant group of bacteria, particularly in soil habitats. At least six
      subdivisions of the Verrucomicrobia are resolved by comparative analysis of 16S
      rRNA genes, mostly obtained directly from environmental samples. To date, only
      two of these subdivisions (1 and 4) have characterized pure-culture
      representatives. We have isolated and characterized the first known pure-culture
      representative of subdivision 2. Strain Ellin428 is an aerobic heterotrophic
      bacterium that is able to grow with many of the saccharide components of plant
      biomass but does not grow with amino acids or organic acids other than pyruvate.
      Cells are yellow, rod-shaped, nonmotile, and gram-stain negative, and they
      contain peptidoglycan with direct cross-linkages of the A1 gamma meso-Dpm type.
      The isolate grows well at 25 degrees C on a variety of standard biological media,
      including some used in the routine cultivation of bacteria from soil. The pH
      range for growth is 4.0 to 7.0. Low levels of menaquinones MK-10 and MK-11 were
      detected. The major cellular fatty acids are C(14:0), a-C(15:0), C(16:1 omega
      7c), and/or 2OH i-C(15:0), and C(16:0). The G+C content of the genomic DNA is 61
      mol%. We propose a new genus and species, Chthoniobacter flavus gen. nov., sp.
      nov., with isolate Ellin428 as the type strain, and a new class for the
      subdivision to which it belongs, Spartobacteria classis nov. Environmental
      sequences indicate that the class Spartobacteria is largely represented by
      globally distributed, abundant, and active soil bacteria.

PMID- 15466528
TI  - Functional analysis of fructosyl-amino acid oxidases of Aspergillus oryzae.
AB  - Three active fractions of fructosyl-amino acid oxidase (FAOD-Ao1, -Ao2a, and 
      Ao2b) were isolated from Aspergillus oryzae strain RIB40. N-terminal and internal
      amino acid sequences of FAOD-Ao2a corresponded to those of FAOD-Ao2b, suggesting
      that these two isozymes were derived from the same protein. FAOD-Ao1 and -Ao2
      were different in substrate specificity and subunit assembly; FAOD-Ao2 was active
      toward N(epsilon)-fructosyl N(alpha)-Z-lysine and fructosyl valine (Fru-Val),
      whereas FAOD-Ao1 was not active toward Fru-Val. The genes encoding the FAOD
      isozymes (i.e., FAOAo1 and FAOAo2) were cloned by PCR with an FAOD-specific
      primer set. The deduced amino acid sequences revealed that FAOD-Ao1 was 50%
      identical to FAOD-Ao2, and each isozyme had a peroxisome-targeting signal-1,
      indicating their localization in peroxisomes. The genes was expressed in
      Escherichia coli and rFaoAo2 showed the same characteristics as FAOD-Ao2, whereas
      rFaoAo1 was not active. FAOAo2 disruptant was obtained by using ptrA as a
      selective marker. Wild-type strain grew on the medium containing Fru-Val as the
      sole carbon and nitrogen sources, but strain Delta faoAo2 did not grow. Addition
      of glucose or (NH(4))(2)SO(4) to the Fru-Val medium did not affect the
      assimilation of Fru-Val by wild-type, indicating glucose and ammonium repressions
      did not occur in the expression of the FAOAo2 gene. Furthermore, conidia of the
      wild-type strain did not germinate on the medium containing Fru-Val and NaNO(2)
      as the sole carbon and nitrogen sources, respectively, suggesting that Fru-Val
      may also repress gene expression of nitrite reductase. These results indicated
      that FAOD is needed for utilization of fructosyl-amino acids as nitrogen sources
      in A. oryzae.

PMID- 15466529
TI  - Expression of an exogenous 1-aminocyclopropane-1-carboxylate deaminase gene in
      Sinorhizobium meliloti increases its ability to nodulate alfalfa.
AB  - 1-Aminocyclopropane-1-carboxylate (ACC) deaminase has been found in various plant
      growth-promoting rhizobacteria, including rhizobia. This enzyme degrades ACC, the
      immediate precursor of ethylene, and thus decreases the biosynthesis of ethylene
      in higher plants. The ACC deaminase of Rhizobium leguminosarum bv. viciae 128C53K
      was previously reported to be able to enhance nodulation of peas. The ACC
      deaminase structural gene (acdS) and its upstream regulatory gene, a leucine
      responsive regulatory protein (LRP)-like gene (lrpL), from R. leguminosarum bv.
      viciae 128C53K were introduced into Sinorhizobium meliloti, which does not
      produce this enzyme, in two different ways: through a plasmid vector and by in
      situ transposon replacement. The resulting ACC deaminase-producing S. meliloti
      strains showed 35 to 40% greater efficiency in nodulating Medicago sativa
      (alfalfa), likely by reducing ethylene production in the host plants.
      Furthermore, the ACC deaminase-producing S. meliloti strain was more competitive
      in nodulation than the wild-type strain. We postulate that the increased
      competitiveness might be related to utilization of ACC as a nutrient within the
      infection threads.

PMID- 15466530
TI  - Pathogenic Aeromonas hydrophila serogroup O:14 and O:81 strains with an S layer.
AB  - Five autoagglutinating Aeromonas hydrophila isolates recovered from eels and
      humans were assigned to serogroups O:14 and O:81 of the Sakazaki and Shimada
      (National Institutes of Health) scheme. They had the following properties in
      common: positive precipitation after boiling, moderate surface hydrophobicity
      (salt-aggregation-test value around 1.2), pathogenicity for fish and mice (50%
      lethal dose, 10(4.61) to 10(7.11)), lipopolysaccharides that contained O
      polysaccharide chains of homogeneous chain length, and an external S layer
      peripheral to the cell wall observed by electron microscopy. A strong cross
      reactivity was detected by immunoblotting between the homogeneous O
      polysaccharide fraction of O:14 and O:81 strains but not between them and the
      lipopolysaccharide of A. hydrophila TF7 (O:11 reference strain). Outer membrane
      fractions of these strains contained a predominant 53- to 54-kDa protein which
      was glycine extractable under low-pH (pH 2.8) conditions and was identified as
      the surface array protein. The S-layer proteins of the O:14 and O:81 A.
      hydrophila strains seemed to be primarily different from those previously
      purified from strains A. hydrophila TF7 and Aeromonas salmonicida A450 on the
      basis of colony hybridizations with both the structural genes vapA and ahsA. This
      is the first report of the presence of an S layer in mesophilic Aeromonas strains
      not belonging to serogroup O:11.

PMID- 15466531
TI  - Oxygen- and glucose-dependent regulation of central carbon metabolism in Pichia
      anomala.
AB  - We investigated the regulation of the central aerobic and hypoxic metabolism of
      the biocontrol and non-Saccharomyces wine yeast Pichia anomala. In aerobic batch
      culture, P. anomala grows in the respiratory mode with a high biomass yield (0.59
      g [dry weight] of cells g of glucose(-1)) and marginal ethanol, glycerol,
      acetate, and ethyl acetate production. Oxygen limitation, but not glucose pulse,
      induced fermentation with substantial ethanol production and 10-fold-increased
      ethyl acetate production. Despite low or absent ethanol formation, the activities
      of pyruvate decarboxylase and alcohol dehydrogenase were high during aerobic
      growth on glucose or succinate. No activation of these enzyme activities was
      observed after a glucose pulse. However, after the shift to oxygen limitation,
      both enzymes were activated threefold. Metabolic flux analysis revealed that the
      tricarboxylic acid pathway operates as a cycle during aerobic batch culture and
      as a two-branched pathway under oxygen limitation. Glucose catabolism through the
      pentose phosphate pathway was lower during oxygen limitation than under aerobic
      growth. Overall, our results demonstrate that P. anomala exhibits a Pasteur
      effect and not a Crabtree effect, i.e., oxygen availability, but not glucose
      concentration, is the main stimulus for the regulation of the central carbon
      metabolism.

PMID- 15466532
TI  - Evaluation of methods for storage of marine macroorganisms with optimal recovery
      of bacteria.
AB  - Marine macroorganisms are a potential source for new bioactive substances. In
      many cases marine microorganisms--especially bacteria--associated with these
      macroorganisms are actually producing the bioactive substances. One often is not
      able to immediately isolate microorganisms from collected macroorganismic
      materials; we therefore evaluated different methods for storage of such material,
      e.g., on board research vessels. These methods were the following: storage of
      macerates in sintered glass beads and 5% trehalose at -20 degrees C (SGT method);
      storage of sections in 5% dimethyl sulfoxide at -70 degrees C (SD method);
      storage of macerates at -20 degrees C using the commercial ROTI-STORE system (RS
      method); storage of macerates at -20 degrees C in 50% glycerol (GC method); and
      storage of macerates covered by mineral oil at 4 degrees C (MO method). The SGT
      and SD methods resulted in numbers of and especially diversity of recoverable
      bacteria that were higher than for the other methods. Data for the RS method
      indicated its potential usefulness, too. The MO method resulted in growth during
      storage, thereby enriching a few selected microorganisms; the GC method resulted
      in a survival and diversity of recovered bacteria that was too low.

PMID- 15466533
TI  - Functional expression of Sinorhizobium meliloti BetS, a high-affinity betaine
      transporter, in Bradyrhizobium japonicum USDA110.
AB  - Among the Rhizobiaceae, Bradyrhizobium japonicum strain USDA110 appears to be
      extremely salt sensitive, and the presence of glycine betaine cannot restore its
      growth in medium with an increased osmolarity (E. Boncompagni, M. Osteras, M. C.
      Poggi, and D. Le Rudulier, Appl. Environ. Microbiol. 65:2072-2077, 1999). In
      order to improve the salt tolerance of B. japonicum, cells were transformed with
      the betS gene of Sinorhizobium meliloti. This gene encodes a major glycine
      betaine/proline betaine transporter from the betaine choline carnitine
      transporter family and is required for early osmotic adjustment. Whereas betaine
      transport was absent in the USDA110 strain, such transformation induced glycine
      betaine and proline betaine uptake in an osmotically dependent manner. Salt
      treated transformed cells accumulated large amounts of glycine betaine, which was
      not catabolized. However, the accumulation was reversed through rapid efflux
      during osmotic downshock. An increased tolerance of transformant cells to a
      moderate NaCl concentration (80 mM) was also observed in the presence of glycine
      betaine or proline betaine, whereas the growth of the wild-type strain was
      totally abolished at 80 mM NaCl. Surprisingly, the deleterious effect due to a
      higher salt concentration (100 mM) could not be overcome by glycine betaine,
      despite a significant accumulation of this compound. Cell viability was not
      significantly affected in the presence of 100 mM NaCl, whereas 75% cell death
      occurred at 150 mM NaCl. The absence of a potential gene encoding Na(+)/H(+)
      antiporters in B. japonicum could explain its very high Na(+) sensitivity.

PMID- 15466534
TI  - New method for estimating bacterial cell abundances in natural samples by use of
      sublimation.
AB  - We have developed a new method based on the sublimation of adenine from
      Escherichia coli to estimate bacterial cell counts in natural samples. To
      demonstrate this technique, several types of natural samples, including beach
      sand, seawater, deep-sea sediment, and two soil samples from the Atacama Desert,
      were heated to a temperature of 500 degrees C for several seconds under reduced
      pressure. The sublimate was collected on a cold finger, and the amount of adenine
      released from the samples was then determined by high-performance liquid
      chromatography with UV absorbance detection. Based on the total amount of adenine
      recovered from DNA and RNA in these samples, we estimated bacterial cell counts
      ranging from approximately 10(5) to 10(9) E. coli cell equivalents per gram. For
      most of these samples, the sublimation-based cell counts were in agreement with
      total bacterial counts obtained by traditional DAPI (4,6-diamidino-2
      phenylindole) staining.

PMID- 15466535
TI  - Improved stress tolerance of GroESL-overproducing Lactococcus lactis and
      probiotic Lactobacillus paracasei NFBC 338.
AB  - The bacterial heat shock response is characterized by the elevated expression of
      a number of chaperone complexes. Two-dimensional polyacrylamide gel
      electrophoresis revealed that GroEL expression in probiotic Lactobacillus
      paracasei NFBC 338 was increased under heat adaptation conditions (52 degrees C
      for 15 min). Subsequently, the groESL operon of L. paracasei NFBC 338 was PCR
      amplified, and by using the nisin-inducible expression system, two plasmids,
      pGRO1 and pGRO2, were constructed on the basis of vectors pNZ8048 and pMSP3535,
      respectively. These vectors were transferred into Lactococcus lactis(pGRO1) and
      L. paracasei(pGRO2), and after induction with nisin, overexpressed GroEL
      represented 15 and 20% of the total cellular protein in each strain,
      respectively. Following heat shock treatment of lactococci (at 54 degrees C) and
      lactobacilli (at 60 degrees C), the heat-adapted cultures maintained the highest
      level of viability (5-log-unit increase, approximately) in each case, while it
      was found that the GroESL-overproducing strains performed only moderately better
      (1-log-unit increase) than the controls. On the other hand, the salt tolerance of
      both GroESL-overproducing strains (in 5 M NaCl) was similar to that of the parent
      cultures. Interestingly, both strains overproducing GroESL exhibited increased
      solvent tolerance, most notably, the ability to grow in the presence of butanol
      (0.5% [vol/vol]) for 5 h, while the viability of the parent strain declined.
      These results confirm the integral role of GroESL in solvent tolerance, and to a
      lesser extent, thermotolerance of lactic acid bacteria. Furthermore, this study
      demonstrates that technologically sensitive cultures, including certain probiotic
      lactobacilli, can potentially be manipulated to become more robust for survival
      under harsh conditions, such as food product development and gastrointestinal
      transit.

PMID- 15466536
TI  - Vulnerability of drinking-water wells in La Crosse, Wisconsin, to enteric-virus
      contamination from surface water contributions.
AB  - Human enteric viruses can contaminate municipal drinking-water wells, but few
      studies have examined the routes by which viruses enter these wells. In the
      present study, the objective was to monitor the municipal wells of La Crosse,
      Wisconsin, for enteric viruses and determine whether the amount of Mississippi
      River water infiltrating the wells was related to the frequency of virus
      detection. From March 2001 to February 2002, one river water site and four wells
      predicted by hydrogeological modeling to have variable degrees of surface water
      contributions were sampled monthly for enteric viruses, microbial indicators of
      sanitary quality, and oxygen and hydrogen isotopes. (18)O/(16)O and (2)H/(1)H
      ratios were used to determine the level of surface water contributions. All
      samples were collected prior to chlorination at the wellhead. By reverse
      transcription-PCR (RT-PCR), 24 of 48 municipal well water samples (50%) were
      positive for enteric viruses, including enteroviruses, rotavirus, hepatitis A
      virus (HAV), and noroviruses. Of 12 river water samples, 10 (83%) were virus
      positive by RT-PCR. Viable enteroviruses were not detected by cell culture in the
      well samples, although three well samples were positive for culturable HAV.
      Enteroviruses detected in the wells by RT-PCR were identified as several
      serotypes of echoviruses and group A and group B coxsackieviruses. None of the
      well water samples was positive for indicators of sanitary quality, namely male
      specific and somatic coliphages, total coliform bacteria, Escherichia coli, and
      fecal enterococci. Contrary to expectations, viruses were found in all wells
      regardless of the level of surface water contributions. This result suggests that
      there were other unidentified sources, in addition to surface water, responsible
      for the contamination.

PMID- 15466537
TI  - High-level genotypic variation and antibiotic sensitivity among Escherichia coli
      O157 strains isolated from two Scottish beef cattle farms.
AB  - Escherichia coli O157:H7 is a human pathogen that is carried and transmitted by
      cattle. Scotland is known to have one of the highest rates of E. coli O157 human
      infections in the world. Two hundred ninety-three isolates were obtained from
      naturally infected cattle and the environment on two farms in the Scottish
      Highlands. The isolates were typed by pulsed-field gel electrophoresis (PFGE)
      with XbaI restriction endonuclease enzyme, and 19 different variations in
      patterns were found. There was considerable genomic diversity within the E. coli
      O157 population on the two farms. The PFGE pattern of one of the observed
      subtypes matched exactly with that of a strain obtained from a Scottish patient
      with hemolytic-uremic syndrome. To examine the stability of an individual E. coli
      O157 strain, continuous subculturing of a strain was performed 110 times. No
      variation from the original PFGE pattern was observed. We found three
      indistinguishable subtypes of E. coli O157 on both study farms, suggesting common
      sources of infection. We also examined the antibiotic resistance of the isolated
      strains. Phenotypic studies demonstrated resistance of the strains to
      sulfamethoxazole (100%), chloramphenicol (3.07%), and at a lower rate, other
      antibiotics, indicating the preservation of antibiotic sensitivity in a rapidly
      changing population of E. coli O157.

PMID- 15466538
TI  - Bacterial community associated with black band disease in corals.
AB  - Black band disease (BBD) is a virulent polymicrobial disease primarily affecting
      massive-framework-building species of scleractinian corals. While it has been
      well established that the BBD bacterial mat is dominated by a cyanobacterium, the
      quantitative composition of the BBD bacterial mat community has not described
      previously. Terminal-restriction fragment length polymorphism (T-RFLP) analysis
      was used to characterize the infectious bacterial community of the bacterial mat
      causing BBD. These analyses revealed that the bacterial composition of the BBD
      mat does not vary between different coral species but does vary when different
      species of cyanobacteria are dominant within the mat. On the basis of the results
      of a new method developed to identify organisms detected by T-RFLP analysis, our
      data show that besides the cyanobacterium, five species of the division
      Firmicutes, two species of the Cytophaga-Flexibacter-Bacteroides (CFB) group, and
      one species of delta-proteobacteria are also consistently abundant within the
      infectious mat. Of these dominant taxa, six were consistently detected in healthy
      corals. However, four of the six were found in much higher numbers in BBD mats
      than in healthy corals. One species of the CFB group and one species of
      Firmicutes were not always associated with the bacterial communities present in
      healthy corals. Of the eight dominant bacteria identified, two species were
      previously found in clone libraries obtained from BBD samples; however, these
      were not previously recognized as important. Furthermore, despite having been
      described as an important component of the pathogenetic mat, a Beggiatoa species
      was not detected in any of the samples analyzed. These results will permit the
      dominant BBD bacteria to be targeted for isolation and culturing experiments
      aimed at deciphering the disease etiology.

PMID- 15466539
TI  - Molecular analysis of geographic patterns of eukaryotic diversity in Antarctic
      soils.
AB  - We describe the application of molecular biological techniques to estimate
      eukaryotic diversity (primarily fungi, algae, and protists) in Antarctic soils
      across a latitudinal and environmental gradient between approximately 60 and 87
      degrees S. The data were used to (i) test the hypothesis that diversity would
      decrease with increasing southerly latitude and environmental severity, as is
      generally claimed for "higher" faunal and plant groups, and (ii) investigate the
      level of endemicity displayed in different taxonomic groups. Only limited support
      was obtained for a systematic decrease in diversity with latitude, and then only
      at the level of a gross comparison between maritime (Antarctic Peninsula/Scotia
      Arc) and continental Antarctic sites. While the most southerly continental
      Antarctic site was three to four times less diverse than all maritime sites,
      there was no evidence for a trend of decreasing diversity across the entire range
      of the maritime Antarctic (60 to 72 degrees S). Rather, we found the reverse
      pattern, with highest diversity at sites on Alexander Island (ca. 72 degrees S),
      at the southern limit of the maritime Antarctic. The very limited overlap found
      between the eukaryotic biota of the different study sites, combined with their
      generally low relatedness to existing sequence databases, indicates a high level
      of Antarctic site isolation and possibly endemicity, a pattern not consistent
      with similar studies on other continents.

PMID- 15466540
TI  - Genome-wide transposon mutagenesis of Borrelia burgdorferi for identification of
      phenotypic mutants.
AB  - The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the
      leading vector-borne illness in the United States. Many of the genetic factors
      affecting spirochete morphology and physiology are unknown due to the limited
      genetic tools available and the large number of open reading frames with unknown
      functions. By adapting a mariner transposon to function in B. burgdorferi, we
      have developed a random mutagenesis system that tags the mutated locus for rapid
      identification. Transposition occurs at saturating levels in B. burgdorferi and
      appears to be random, targeting both linear and circular replicons. By combining
      the transposon system with a screen for factors affecting growth rate, mutations
      were readily identified in genes putatively involved in cell division and
      chemotaxis and a hypothetical open reading frame involved in outer membrane
      integrity. The successful adaptation of a mariner transposon to function in B.
      burgdorferi should aid in identifying virulence factors and novel gene products
      related to spirochete physiology.

PMID- 15466541
TI  - Unexpectedly diverse Mesorhizobium strains and Rhizobium leguminosarum nodulate
      native legume genera of New Zealand, while introduced legume weeds are nodulated
      by Bradyrhizobium species.
AB  - The New Zealand native legume flora are represented by four genera, Sophora,
      Carmichaelia, Clianthus, and Montigena. The adventive flora of New Zealand
      contains several legume species introduced in the 19th century and now
      established as serious invasive weeds. Until now, nothing has been reported on
      the identification of the associated rhizobia of native or introduced legumes in
      New Zealand. The success of the introduced species may be due, at least in part,
      to the nature of their rhizobial symbioses. This study set out to address this
      issue by identifying rhizobial strains isolated from species of the four native
      legume genera and from the introduced weeds: Acacia spp. (wattles), Cytisus
      scoparius (broom), and Ulex europaeus (gorse). The identities of the isolates and
      their relationship to known rhizobia were established by comparative analysis of
      16S ribosomal DNA, atpD, glnII, and recA gene sequences. Maximum-likelihood
      analysis of the resultant data partitioned the bacteria into three genera. Most
      isolates from native legumes aligned with the genus Mesorhizobium, either as
      members of named species or as putative novel species. The widespread
      distribution of strains from individual native legume genera across Mesorhizobium
      spp. contrasts with previous reports implying that bacterial species are specific
      to limited numbers of legume genera. In addition, four isolates were identified
      as Rhizobium leguminosarum. In contrast, all sequences from isolates from
      introduced weeds aligned with Bradyrhizobium species but formed clusters distinct
      from existing named species. These results show that native legume genera and
      these introduced legume genera do not have the same rhizobial populations.

PMID- 15466542
TI  - Enzymatic analysis of an amylolytic enzyme from the hyperthermophilic archaeon
      Pyrococcus furiosus reveals its novel catalytic properties as both an alpha
      amylase and a cyclodextrin-hydrolyzing enzyme.
AB  - Genomic analysis of the hyperthermophilic archaeon Pyrococcus furiosus revealed
      the presence of an open reading frame (ORF PF1939) similar to the enzymes in
      glycoside hydrolase family 13. This amylolytic enzyme, designated PFTA
      (Pyrococcus furiosus thermostable amylase), was cloned and expressed in
      Escherichia coli. The recombinant PFTA was extremely thermostable, with an
      optimum temperature of 90 degrees C. The substrate specificity of PFTA suggests
      that it possesses characteristics of both alpha-amylase and cyclodextrin
      hydrolyzing enzyme. Like typical alpha-amylases, PFTA hydrolyzed
      maltooligosaccharides and starch to produce mainly maltotriose and maltotetraose.
      However, it could also attack and degrade pullulan and beta-cyclodextrin, which
      are resistant to alpha-amylase, to primarily produce panose and maltoheptaose,
      respectively. Furthermore, acarbose, a potent alpha-amylase inhibitor, was
      drastically degraded by PFTA, as is typical of cyclodextrin-hydrolyzing enzymes.
      These results confirm that PFTA possesses novel catalytic properties
      characteristic of both alpha-amylase and cyclodextrin-hydrolyzing enzyme.

PMID- 15466544
TI  - Multiple-antibiotic resistance of Enterococcus spp. isolated from commercial
      poultry production environments.
AB  - The potential impact of food animals in the production environment on the
      bacterial population as a result of antimicrobial drug use for growth enhancement
      continues to be a cause for concern. Enterococci from 82 farms within a poultry
      production region on the eastern seaboard were isolated to establish a baseline
      of susceptibility profiles for a number of antimicrobials used in production as
      well as clinical environments. Of the 541 isolates recovered, Enterococcus
      faecalis (53%) and E. faecium (31%) were the predominant species, while
      multiresistant antimicrobial phenotypes were observed among all species. The
      prevalence of resistance among isolates of E. faecalis was comparatively higher
      among lincosamide, macrolide, and tetracycline antimicrobials, while isolates of
      E. faecium were observed to be more frequently resistant to fluoroquinolones and
      penicillins. Notably, 63% of the E. faecium isolates were resistant to the
      streptogramin quinupristin-dalfopristin, while high-level gentamicin resistance
      was observed only among the E. faecalis population, of which 7% of the isolates
      were resistant. The primary observations are that enterococci can be frequently
      isolated from the poultry production environment and can be multiresistant to
      antimicrobials used in human medicine. The high frequency with which resistant
      enterococci are isolated from this environment suggests that these organisms
      might be useful as sentinels to monitor the development of resistance resulting
      from the usage of antimicrobial agents in animal production.

PMID- 15466543
TI  - Molecular detection and genotyping of male-specific coliphages by reverse
      transcription-PCR and reverse line blot hybridization.
AB  - In recent years, there has been increased interest in the use of male-specific or
      F+ coliphages as indicators of microbial inputs to source waters. Sero- or
      genotyping of these coliphages can also be used for microbial source tracking
      (MST). Among the male-specific coliphages, the F+ RNA (FRNA) viruses are well
      studied, while little is known about the F+ DNA (FDNA) viruses. We have developed
      a reverse line blot hybridization (RLB) assay which allows for the simultaneous
      detection and genotyping of both FRNA as well as FDNA coliphages. These assays
      included a novel generic duplex reverse transcription-PCR (RT-PCR) assay for FRNA
      viruses as well as a generic PCR for FDNA viruses. The RT-PCR assays were
      validated by using 190 field and prototype strains. Subsequent DNA sequencing and
      phylogenetic analyses of RT-PCR products revealed the classification of six
      different FRNA clusters, including the well-established subgroups I through IV,
      and three different FDNA clusters, including one (CH) not previously described.
      Within the leviviruses, a potentially new subgroup (called JS) including strains
      having more than 40% nucleotide sequence diversity with the known levivirus
      subgroups (MS2 and GA) was identified. We designed subgroup-specific
      oligonucleotides that were able to genotype all nine (six FRNA, three FDNA)
      different clusters. Application of the method to a panel of 351 enriched phage
      samples from animal feces and wastewater, including known prototype strains (MS2,
      GA, Q beta, M11, FI, and SP for FRNA and M13, f1, and fd for FDNA), resulted in
      successful genotyping of 348 (99%) of the samples. In summary, we developed a
      novel method for standardized genotyping of F+ coliphages as a useful tool for
      large-scale MST studies.

PMID- 15466545
TI  - Nanoscale investigation of pathogenic microbial adhesion to a biomaterial.
AB  - Microbial infections of medical implants occur in more than 2 million surgical
      cases each year in the United States alone. These increase patient morbidity and
      mortality, as well as patient cost and recovery time. Many treatments are
      available, but none are guaranteed to remove the infection. In many cases, the
      device infections are caused by the adhesion of microbes to the implant, ensuing
      growth, pathogenesis, and dissemination. The purpose of this work is to examine
      the initial events in microbial adhesion by simulating the approach and contact
      between a planktonic cell, immobilized on an atomic force microscope (AFM)
      cantilever, and a biomaterial or biofilm substrate. The two model microbes used
      in this study, Candida parapsilosis (ATCC 90018) and Pseudomonas aeruginosa (ATCC
      10145), were chosen for both their clinical relevance and their ease of
      acquisition and handling in the laboratory setting. Attractive interactions exist
      between C. parapsilosis and both unmodified silicone rubber and P. aeruginosa
      biofilms. Using C. parapsilosis cells immobilized on AFM cantilevers with a
      silicone substrate, we have measured attractive forces of 4.3 +/- 0.25 nN in the
      approach portion of the force cycle. On P. aeruginosa biofilms, the magnitude of
      the attractive force decreases to 2.0 +/- 0.40 nN and is preceded by a 2.0-nN
      repulsion at approximately 75 nm from the cell surface. These data suggest that
      C. parapsilosis may adhere to both silicone rubber and P. aeruginosa biofilms,
      possibly contributing to patient morbidity and mortality. Characterization of
      cell-biomaterial and cell-cell interactions allows for a quantitative link
      between the physicomechanical and physicochemical properties of implant materials
      and the nanoscale interactions leading to microbial colonization and infection.

PMID- 15466546
TI  - Potential role of a novel psychrotolerant member of the family Geobacteraceae,
      Geopsychrobacter electrodiphilus gen. nov., sp. nov., in electricity production
      by a marine sediment fuel cell.
AB  - Previous studies have shown that members of the family Geobacteraceae that attach
      to the anodes of sediment fuel cells are directly involved in harvesting
      electricity by oxidizing organic compounds to carbon dioxide and transferring the
      electrons to the anode. In order to learn more about this process, microorganisms
      from the anode surface of a marine sediment fuel cell were enriched and isolated
      with Fe(III) oxide. Two unique marine isolates were recovered, strains A1(T) and
      A2. They are gram-negative, nonmotile rods, with abundant c-type cytochromes.
      Phylogenetic analysis of the 16S rRNA, recA, gyrB, fusA, rpoB, and nifD genes
      indicated that strains A1(T) and A2 represent a unique phylogenetic cluster
      within the Geobacteraceae. Both strains were able to grow with an electrode
      serving as the sole electron acceptor and transferred ca. 90% of the electrons
      available in their organic electron donors to the electrodes. These organisms are
      the first psychrotolerant members of the Geobacteraceae reported thus far and can
      grow at temperatures between 4 and 30 degrees C, with an optimum temperature of
      22 degrees C. Strains A1(T) and A2 can utilize a wide range of traditional
      electron acceptors, including all forms of soluble and insoluble Fe(III) tested,
      anthraquinone 2,6-disulfonate, and S(0). In addition to acetate, both strains can
      utilize a number of other organic acids, amino acids, long-chain fatty acids, and
      aromatic compounds to support growth with Fe(III) nitrilotriacetic acid as an
      electron acceptor. The metabolism of these organisms differs in that only strain
      A1(T) can use acetoin, ethanol, and hydrogen as electron donors, whereas only
      strain A2 can use lactate, propionate, and butyrate. The name Geopsychrobacter
      electrodiphilus gen. nov., sp. nov., is proposed for strains A1(T) and A2, with
      strain A1(T) (ATCC BAA-880(T); DSM 16401(T); JCM 12469) as the type strain.
      Strains A1(T) and A2 (ATCC BAA-770; JCM 12470) represent the first organisms
      recovered from anodes that can effectively couple the oxidation of organic
      compounds to an electrode. Thus, they may serve as important model organisms for
      further elucidation of the mechanisms of microbe-electrode electron transfer in
      sediment fuel cells.

PMID- 15466547
TI  - Accelerated biodegradation of cement by sulfur-oxidizing bacteria as a bioassay
      for evaluating immobilization of low-level radioactive waste.
AB  - Disposal of low-level radioactive waste by immobilization in cement is being
      evaluated worldwide. The stability of cement in the environment may be impaired
      by sulfur-oxidizing bacteria that corrode the cement by producing sulfuric acid.
      Since this process is so slow that it is not possible to perform studies of the
      degradation kinetics and to test cement mixtures with increased durability,
      procedures that accelerate the biodegradation are required. Semicontinuous
      cultures of Halothiobacillus neapolitanus and Thiomonas intermedia containing
      thiosulfate as the sole energy source were employed to accelerate the
      biodegradation of cement samples. This resulted in a weight loss of up to 16%
      after 39 days, compared with a weight loss of 0.8% in noninoculated controls.
      Scanning electron microscopy of the degraded cement samples revealed deep cracks,
      which could be associated with the formation of low-density corrosion products in
      the interior of the cement. Accelerated biodegradation was also evident from the
      leaching rates of Ca(2+) and Si(2+), the major constituents of the cement matrix,
      and Ca exhibited the highest rate (up to 20 times greater than the control rate)
      due to the reaction between free lime and the biogenic sulfuric acid. Leaching of
      Sr(2+) and Cs(+), which were added to the cement to simulate immobilization of
      the corresponding radioisotopes, was also monitored. In contrast to the linear
      leaching kinetics of calcium, silicon, and strontium, the leaching pattern of
      cesium produced a saturation curve similar to the control curve. Presumably, the
      leaching of cesium is governed by the diffusion process, whereas the leaching
      kinetics of the other three ions seems to governed by dissolution of the cement.

PMID- 15466549
TI  - Galactose metabolism by Streptococcus mutans.
AB  - The galK gene, encoding galactokinase of the Leloir pathway, was insertionally
      inactivated in Streptococcus mutans UA159. The galK knockout strain displayed
      only marginal growth on galactose, but growth on glucose or lactose was not
      affected. In strain UA159, the sugar phosphotransferase system (PTS) for lactose
      and the PTS for galactose were induced by growth in lactose and galactose,
      although galactose PTS activity was very low, suggesting that S. mutans does not
      have a galactose-specific PTS and that the lactose PTS may transport galactose,
      albeit poorly. To determine if the galactose growth defect of the galK mutant
      could be overcome by enhancing lactose PTS activity, the gene encoding a putative
      repressor of the operon for lactose PTS and phospho-beta-galactosidase, lacR, was
      insertionally inactivated. A galK and lacR mutant still could not grow on
      galactose, although the strain had constitutively elevated lactose PTS activity.
      The glucose PTS activity of lacR mutants grown in glucose was lower than in the
      wild-type strain, revealing an influence of LacR or the lactose PTS on the
      regulation of the glucose PTS. Mutation of the lacA gene of the tagatose pathway
      caused impaired growth in lactose and galactose, suggesting that galactose can
      only be efficiently utilized when both the Leloir and tagatose pathways are
      functional. A mutation of the permease in the multiple sugar metabolism operon
      did not affect growth on galactose. Thus, the galactose permease of S. mutans is
      not present in the gal, lac, or msm operons.

PMID- 15466548
TI  - Composition and diversity of microbial communities recovered from surrogate
      minerals incubated in an acidic uranium-contaminated aquifer.
AB  - Our understanding of subsurface microbiology is hindered by the inaccessibility
      of this environment, particularly when the hydrogeologic medium is contaminated
      with toxic substances. In this study, surrogate geological media contained in a
      porous receptacle were incubated in a well within the saturated zone of a
      pristine region of an aquifer to capture populations from the extant communities.
      After an 8-week incubation, the media were recovered, and the microbial community
      that developed on each medium was compared to the community recovered from
      groundwater and native sediments from the same region of the aquifer, using 16S
      DNA coding for rRNA (rDNA)-based terminal restriction fragment length
      polymorphism (T-RFLP). The groundwater and sediment communities were highly
      distinct from one another, and the communities that developed on the various
      media were more similar to groundwater communities than to sediment communities.
      16S rDNA clone libraries of communities that developed on particles of a specular
      hematite medium incubated in the same well as the media used for T-RFLP analysis
      were compared with those obtained from an acidic, uranium-contaminated region of
      the same aquifer. The hematite-associated community formed in the pristine area
      was highly diverse at the species level, with 25 distinct phylotypes identified,
      the majority of which (73%) were affiliated with the beta-Proteobacteria.
      Similarly, the hematite-associated community formed in the contaminated area was
      populated in large part by beta-Proteobacteria (62%); however, only 13 distinct
      phylotypes were apparent. The three numerically dominant clones from the hematite
      associated community from the contaminated site were affiliated with metal- and
      radionuclide-tolerant or acidophilic taxa, consistent with the environmental
      conditions. Only two populations were common to both sites.

PMID- 15466550
TI  - Reduction of Escherichia coli O157:H7 populations in cattle by addition of
      colicin E7-producing E. coli to feed.
AB  - A cattle trial using artificially inoculated calves was conducted to determine
      the effect of the addition of colicinogenic Escherichia coli strains capable of
      producing colicin E7 (a 61-kDa DNase) to feed on the fecal shedding of serotype
      O157:H7. The experiment was divided into three periods. In period 1, which lasted
      24 days, six calves were used as controls, and eight calves received 10(7) CFU of
      E. coli (a mixture of eight colicinogenic E. coli strains) per g of feed. Both
      groups were orally inoculated with nalidixic acid-resistant E. coli O157:H7
      strains 7 days after the treatment started. In periods 2 and 3, the treatment and
      control groups were switched, and the colicinogenic E. coli dose was increased 10
      fold. During period 3, which lasted as long as period 1, both groups were
      reinoculated with E. coli O157:H7. The numbers of E. coli O157:H7 were
      consistently greater in the control groups during the three periods, but
      comparisons within each time period determined a statistically significant (P <
      0.05) difference only at day 21 of period 1. However, when the daily average
      counts were compared between the period 1 control group and the period 3
      treatment group that included the same six animals, an overall reduction of 1.1
      log(10) CFU/g was observed, with a maximum decrease of 1.8 log(10) CFU/g at day
      21 (overall statistical significance, P = 0.001). Serotype O157:H7 was detected
      in 44% of the treatment group's intestinal tissue samples and in 64% of those
      from the control group (P < 0.04). These results indicated that the daily
      addition of 10(8) CFU of colicin E7-producing E. coli per gram of feed could
      reduce the fecal shedding of serotype O157:H7.

PMID- 15466551
TI  - Influence of apple cultivars on inactivation of different strains of Escherichia
      coli O157:H7 in apple cider by UV irradiation.
AB  - This study examined the effect of different apple cultivars upon the UV
      inactivation of Escherichia coli O157:H7 strains within unfiltered apple cider.
      Apple cider was prepared from eight different apple cultivars, inoculated with
      approximately 10(6) to 10(7) CFU of three strains of E. coli O157:H7 per ml (933,
      ATCC 43889, and ATCC 43895), and exposed to 14 mJ of UV irradiation per cm(2).
      Bacterial populations for treated and untreated samples were then enumerated by
      using nonselective media. E. coli O157:H7 ATCC 43889 showed the most sensitivity
      to this disinfection process with an average 6.63-log reduction compared to an
      average log reduction of 5.93 for both strains 933 and ATCC 43895. The highest
      log reduction seen, 7.19, occurred for strain ATCC 43889 in Rome cider. The same
      cider produced the lowest log reductions: 5.33 and 5.25 for strains 933 and ATCC
      43895, respectively. Among the apple cultivars, an average log reduction range of
      5.78 (Red Delicious) to 6.74 (Empire) was observed, with two statistically
      significant (alpha < or = 0.05) log reduction groups represented. Within the
      paired cultivar-strain analysis, five of eight ciders showed statistically
      significant (alpha < or = 0.05) differences in at least two of the E. coli
      strains used. Comparison of log reductions among the E. coli strains to the cider
      parameters of (o)Brix, pH, and malic acid content failed to show any
      statistically significant relationship (R(2) > or = 0.95). However, the results
      of this study indicate that regardless of the apple cultivar used, a minimum 5
      log reduction is achieved for all of the strains of E. coli O157:H7 tested.

PMID- 15466552
TI  - Genetic analysis of phenoxyalkanoic acid degradation in Sphingomonas
      herbicidovorans MH.
AB  - Phenoxyalkanoic acid degradation is well studied in Beta- and
      Gammaproteobacteria, but the genetic background has not been elucidated so far in
      Alphaproteobacteria. We report the isolation of several genes involved in dichlor
      and mecoprop degradation from the alphaproteobacterium Sphingomonas
      herbicidovorans MH and propose that the degradation proceeds analogously to that
      previously reported for 2,4-dichlorophenoxyacetic acid (2,4-D). Two genes for
      alpha-ketoglutarate-dependent dioxygenases, sdpA(MH) and rdpA(MH), were found,
      both of which were adjacent to sequences with potential insertion elements.
      Furthermore, a gene for a dichlorophenol hydroxylase (tfdB), a putative
      regulatory gene (cadR), two genes for dichlorocatechol 1,2-dioxygenases
      (dccA(I/II)), two for dienelactone hydrolases (dccD(I/II)), part of a gene for
      maleylacetate reductase (dccE), and one gene for a potential phenoxyalkanoic acid
      permease were isolated. In contrast to other 2,4-D degraders, the sdp, rdp, and
      dcc genes were scattered over the genome and their expression was not tightly
      regulated. No coherent pattern was derived on the possible origin of the sdp,
      rdp, and dcc pathway genes. rdpA(MH) was 99% identical to rdpA(MC1), an (R)
      dichlorprop/alpha-ketoglutarate dioxygenase from Delftia acidovorans MC1, which
      is evidence for a recent gene exchange between Alpha- and Betaproteobacteria.
      Conversely, DccA(I) and DccA(II) did not group within the known chlorocatechol
      1,2-dioxygenases, but formed a separate branch in clustering analysis. This
      suggests a different reservoir and reduced transfer for the genes of the modified
      ortho-cleavage pathway in Alphaproteobacteria compared with the ones in Beta- and
      Gammaproteobacteria.

PMID- 15466553
TI  - Novel cassette-based shuttle vector system for gram-positive bacteria.
AB  - Our understanding of staphylococcal pathogenesis depends on reliable genetic
      tools for gene expression analysis and tracing of bacteria. Here, we have
      developed and evaluated a series of novel versatile Escherichia coli
      staphylococcal shuttle vectors based on PCR-generated interchangeable cassettes.
      Advantages of our module system include the use of (i) staphylococcal low-copy
      number, high-copy-number, thermosensitive and theta replicons and selectable
      markers (choice of erythromycin, tetracycline, chloramphenicol, kanamycin, or
      spectinomycin); (ii) an E. coli replicon and selectable marker (ampicillin); and
      (iii) a staphylococcal phage fragment that allows high-frequency transduction and
      an SaPI fragment that allows site-specific integration into the Staphylococcus
      aureus chromosome. The staphylococcal cadmium-inducible P(cad)-cadC and
      constitutive P(blaZ) promoters were designed and analyzed in transcriptional
      fusions to the staphylococcal beta-lactamase blaZ, the Vibrio fischeri luxAB, and
      the Aequorea victoria green fluorescent protein reporter genes. The modular
      design of the vector system provides great flexibility and variety. Questions
      about gene dosage, complementation, and cis-trans effects can now be conveniently
      addressed, so that this system constitutes an effective tool for studying gene
      regulation of staphylococci in various ecosystems.

PMID- 15466554
TI  - Production of L-ascorbic acid by metabolically engineered Saccharomyces
      cerevisiae and Zygosaccharomyces bailii.
AB  - Yeasts do not possess an endogenous biochemical pathway for the synthesis of
      vitamin C. However, incubated with l-galactose, L-galactono-1,4-lactone, or L
      gulono-1,4-lactone intermediates from the plant or animal pathway leading to l
      ascorbic acid, Saccharomyces cerevisiae and Zygosaccharomyces bailii cells
      accumulate the vitamin intracellularly. Overexpression of the S. cerevisiae
      enzymes d-arabinose dehydrogenase and D-arabinono-1,4-lactone oxidase enhances
      this ability significantly. In fact, the respective recombinant yeast strains
      even gain the capability to accumulate the vitamin in the culture medium. An even
      better result is obtainable by expression of the plant enzyme L-galactose
      dehydrogenase from Arabidopsis thaliana. Budding yeast cells overexpressing the
      endogenous D-arabinono-1,4-lactone oxidase as well as L-galactose dehydrogenase
      are capable of producing about 100 mg of L-ascorbic acid liter(-1), converting
      40% (wt/vol) of the starting compound L-galactose.

PMID- 15466555
TI  - Involvement of linear plasmids in aerobic biodegradation of vinyl chloride.
AB  - Pseudomonas putida strain AJ and Ochrobactrum strain TD were isolated from
      hazardous waste sites based on their ability to use vinyl chloride (VC) as the
      sole source of carbon and energy under aerobic conditions. Strains AJ and TD also
      use ethene and ethylene oxide as growth substrates. Strain AJ contained a linear
      megaplasmid (approximately 260 kb) when grown on VC or ethene, but it contained
      no circular plasmids. While strain AJ was growing on ethylene oxide, it was
      observed to contain a 100-kb linear plasmid, and its ability to use VC as a
      substrate was retained. The linear plasmids in strain AJ were cured, and the
      ability of strain AJ to consume VC, ethene, and ethylene oxide was lost following
      growth on a rich substrate (Luria-Bertani broth) through at least three
      transfers. Strain TD contained three linear plasmids, ranging in size from
      approximately 90 kb to 320 kb, when growing on VC or ethene. As with strain AJ,
      the linear plasmids in strain TD were cured following growth on Luria-Bertani
      broth and its ability to consume VC and ethene was lost. Further analysis of
      these linear plasmids may help reveal the pathway for VC biodegradation in
      strains AJ and TD and explain why this process occurs at many but not all sites
      where groundwater is contaminated with chloroethenes. Metabolism of VC and ethene
      by strains AJ and TD is initiated by an alkene monooxygenase. Their yields during
      growth on VC (0.15 to 0.20 mg of total suspended solids per mg of VC) are similar
      to the yields reported for other isolates (i.e., Mycobacterium sp., Nocardioides
      sp., and Pseudomonas sp.).

PMID- 15466557
TI  - Comparison of compositions and metabolic activities of fecal microbiotas in young
      adults and in antibiotic-treated and non-antibiotic-treated elderly subjects.
AB  - The colonic microbiota mediates many cellular and molecular events in the host
      that are important to health. These processes can be affected in the elderly,
      because in some individuals, the composition and metabolic activities of the
      microbiota change with age. Detailed characterizations of the major groups of
      fecal bacteria in healthy young adults, in healthy elderly people, and in
      hospitalized elderly patients receiving antibiotics were made in this study,
      together with measurements of their metabolic activities, by analysis of fecal
      organic acid and ammonia concentrations. The results showed that total anaerobe
      numbers remained relatively constant in old people; however, individual bacterial
      genera changed markedly with age. Reductions in numbers of bacteroides and
      bifidobacteria in both elderly groups were accompanied by reduced species
      diversity. Bifidobacterial populations in particular showed marked variations in
      the dominant species, with Bifidobacterium angulatum and Bifidobacterium
      adolescentis being frequently isolated from the elderly and Bifidobacterium
      longum, Bifidobacterium catenulatum, Bifidobacterium boum, and Bifidobacterium
      infantis being detected only from the healthy young volunteers. Reductions in
      amylolytic activities of bacterial isolates in healthy elderly subjects and
      reduced short-chain fatty acid concentrations supported these findings, since
      bifidobacteria and bacteroides are important saccharolytic groups in the colon.
      Conversely, higher numbers of proteolytic bacteria were observed with feces
      samples from the antibiotic-treated elderly group, which were also associated
      with increased proteolytic species diversity (fusobacteria, clostridia, and
      propionibacteria). Other differences in the intestinal ecosystem in elderly
      subjects were observed, with alterations in the dominant clostridial species in
      combination with greater numbers of facultative anaerobes.

PMID- 15466556
TI  - Transcriptional analysis of biofilm formation processes in the anaerobic,
      hyperthermophilic bacterium Thermotoga maritima.
AB  - Thermotoga maritima, a fermentative, anaerobic, hyperthermophilic bacterium, was
      found to attach to bioreactor glass walls, nylon mesh, and polycarbonate filters
      during chemostat cultivation on maltose-based media at 80 degrees C. A whole
      genome cDNA microarray was used to examine differential expression patterns
      between biofilm and planktonic populations. Mixed-model statistical analysis
      revealed differential expression (twofold or more) of 114 open reading frames in
      sessile cells (6% of the genome), over a third of which were initially annotated
      as hypothetical proteins in the T. maritima genome. Among the previously
      annotated genes in the T. maritima genome, which showed expression changes during
      biofilm growth, were several that corresponded to biofilm formation genes
      identified in mesophilic bacteria (i.e., Pseudomonas species, Escherichia coli,
      and Staphylococcus epidermidis). Most notably, T. maritima biofilm-bound cells
      exhibited increased transcription of genes involved in iron and sulfur transport,
      as well as in biosynthesis of cysteine, thiamine, NAD, and isoprenoid side chains
      of quinones. These findings were all consistent with the up-regulation of iron
      sulfur cluster assembly and repair functions in biofilm cells. Significant up
      regulation of several beta-specific glycosidases was also noted in biofilm cells,
      despite the fact that maltose was the primary carbon source fed to the chemostat.
      The reasons for increased beta-glycosidase levels are unclear but are likely
      related to the processing of biofilm-based polysaccharides. In addition to
      revealing insights into the phenotype of sessile T. maritima communities, the
      methodology developed here can be extended to study other anaerobic biofilm
      formation processes as well as to examine aspects of microbial ecology in
      hydrothermal environments.

PMID- 15466558
TI  - Helix 4 mutants of the Bacillus thuringiensis insecticidal toxin Cry1Aa display
      altered pore-forming abilities.
AB  - The role played by alpha-helix 4 of the Bacillus thuringiensis toxin Cry1Aa in
      pore formation was investigated by individually replacing each of its charged
      residues with either a neutral or an oppositely charged amino acid by using site
      directed mutagenesis. The majority of the resulting mutant proteins were
      considerably less toxic to Manduca sexta larvae than Cry1Aa. Most mutants also
      had a considerably reduced ability to form pores in midgut brush border membrane
      vesicles isolated from this insect, with the notable exception of those with
      alterations at amino acid position 127 (R127N and R127E), located near the N
      terminal end of the helix. Introducing a negatively charged amino acid near the C
      terminal end of the helix (T142D and T143D), a region normally devoid of charged
      residues, completely abolished pore formation. For each mutant that retained
      detectable pore-forming activity, reduced membrane permeability to KCl was
      accompanied by an approximately equivalent reduction in permeability to N-methyl
      D-glucamine hydrochloride, potassium gluconate, sucrose, and raffinose and by a
      reduced rate of pore formation. These results indicate that the main effect of
      the mutations was to decrease the toxin's ability to form pores. They provide
      further evidence that alpha-helix 4 plays a crucial role in the mechanism of pore
      formation.

PMID- 15466559
TI  - Cloning and expression of a phloretin hydrolase gene from Eubacterium ramulus and
      characterization of the recombinant enzyme.
AB  - Phloretin hydrolase catalyzes the hydrolytic C-C cleavage of phloretin to
      phloroglucinol and 3-(4-hydroxyphenyl)propionic acid during flavonoid degradation
      in Eubacterium ramulus. The gene encoding the enzyme was cloned by screening a
      gene library for hydrolase activity. The insert of a clone conferring phloretin
      hydrolase activity was sequenced. Sequence analysis revealed an open reading
      frame of 822 bp (phy), a putative promoter region, and a terminating stem-loop
      structure. The deduced amino acid sequence of phy showed similarities to a
      putative protein of the 2,4-diacetylphloroglucinol biosynthetic operon from
      Pseudomonas fluorescens. The phloretin hydrolase was heterologously expressed in
      Escherichia coli and purified. The molecular mass of the native enzyme was
      approximately 55 kDa as determined by gel filtration. The results of sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and the deduced amino acid
      sequence of phy indicated molecular masses of 30 and 30.8 kDa, respectively,
      suggesting that the enzyme is a homodimer. The recombinant phloretin hydrolase
      catalyzed the hydrolysis of phloretin to equimolar amounts of phloroglucinol and
      3-(4-hydroxyphenyl)propionic acid. The optimal temperature and pH of the
      catalyzed reaction mixture were 37 degrees C and 7.0, respectively. The K(m) for
      phloretin was 13 +/- 3 microM and the k(cat) was 10 +/- 2 s(-1). The enzyme did
      not transform phloretin-2'-glucoside (phloridzin), neohesperidin dihydrochalcone,
      1,3-diphenyl-1,3-propandione, or trans-1,3-diphenyl-2,3-epoxy-propan-1-one. The
      catalytic activity of the phloretin hydrolase was reduced by N-bromosuccinimide,
      o-phenanthroline, N-ethylmaleimide, and CuCl(2) to 3, 20, 35, and 85%,
      respectively. Phloroglucinol and 3-(4-hydroxyphenyl)propionic acid reduced the
      activity to 54 and 70%, respectively.

PMID- 15466560
TI  - Detection of low levels of Listeria monocytogenes cells by using a fiber-optic
      immunosensor.
AB  - Biosensor technology has a great potential to meet the need for sensitive and
      nearly real-time microbial detection from foods. An antibody-based fiber-optic
      biosensor to detect low levels of Listeria monocytogenes cells following an
      enrichment step was developed. The principle of the sensor is a sandwich
      immunoassay where a rabbit polyclonal antibody was first immobilized on
      polystyrene fiber waveguides through a biotin-streptavidin reaction to capture
      Listeria cells on the fiber. Capture of cells on the fibers was confirmed by
      scanning electron microscopy. A cyanine 5-labeled murine monoclonal antibody,
      C11E9, was used to generate a specific fluorescent signal, which was acquired by
      launching a 635-nm laser light from an Analyte 2000 and collected by a
      photodetector at 670 to 710 nm. This immunosensor was specific for L.
      monocytogenes and showed a significantly higher signal strength than for other
      Listeria species or other microorganisms, including Escherichia coli,
      Enterococcus faecalis, Salmonella enterica, Lactobacillus plantarum,
      Carnobacterium gallinarum, Hafnia alvei, Corynebacterium glutamicum, Enterobacter
      aerogenes, Pseudomonas aeruginosa, and Serratia marcescens, in pure or in mixed
      culture setup. Fiber-optic results could be obtained within 2.5 h of sampling.
      The sensitivity threshold was about 4.3 x 10(3) CFU/ml for a pure culture of L.
      monocytogenes grown at 37 degrees C. When L. monocytogenes was mixed with lactic
      acid bacteria or grown at 10 degrees C with 3.5% NaCl, the detection threshold
      was 4.1 x 10(4) or 2.8 x 10(7) CFU/ml, respectively. In less than 24 h, this
      method could detect L. monocytogenes in hot dog or bologna naturally contaminated
      or artificially inoculated with 10 to 1,000 CFU/g after enrichment in buffered
      Listeria enrichment broth.

PMID- 15466561
TI  - Comparison of different primer sets for use in automated ribosomal intergenic
      spacer analysis of complex bacterial communities.
AB  - ITSF and ITSReub, constituting a new primer set designed for the amplification of
      the 16S-23S rRNA intergenic transcribed spacers, have been compared with primer
      sets consisting of 1406F and 23Sr (M. M. Fisher and E. W. Triplett, Appl.
      Environ. Microbiol. 65:4630-4636, 1999) and S-D-Bact-1522-b-S-20 and L-D-Bact-132
      a-A-18 (L. Ranjard et al., Appl. Environ. Microbiol. 67:4479-4487, 2001),
      previously proposed for automated ribosomal intergenic spacer analysis (ARISA) of
      complex bacterial communities. An agricultural soil and a polluted soil, maize
      silage, goat milk, a small marble sample from the facade of the Certosa of Pavia
      (Pavia, Italy), and brine from a deep hypersaline anoxic basin in the
      Mediterranean Sea were analyzed with the three primer sets. The number of peaks
      in the ARISA profiles, the range of peak size (width of the profile), and the
      reproducibility of results were used as indices to evaluate the efficiency of the
      three primer sets. The overall data showed that ITSF and ITSReub generated the
      most informative (in term of peak number) and reproducible profiles and yielded a
      wider range of spacer sizes (134 to 1,387) than the other primer sets, which were
      limited in detecting long fragments. The minimum amount of DNA template and
      sensitivity in detection of minor DNA populations were evaluated with artificial
      mixtures of defined bacterial species. ITSF and ITSReub amplified all the
      bacteria at DNA template concentrations from 280 to 0.14 ng microl(-1), while the
      other primer sets failed to detect the spacers of one or more bacterial strains.
      Although the primer set consisting of ITSF and ITSReub and that of S-D-Bact-1522
      b-S-20 and L-D-Bact-132-a-A-18 showed similar sensitivities for the DNA of
      Allorhizobium undicula mixed with the DNA of other species, the S-D-Bact-1522-b-S
      20 and L-D-Bact-132-a-A-18 primer set failed to detect the DNA of Pseudomonas
      stutzeri.

PMID- 15466562
TI  - Discrimination of modes of action of antifungal substances by use of metabolic
      footprinting.
AB  - Diploid cells of Saccharomyces cerevisiae were grown under controlled conditions
      with a Bioscreen instrument, which permitted the essentially continuous
      registration of their growth via optical density measurements. Some cultures were
      exposed to concentrations of a number of antifungal substances with different
      targets or modes of action (sterol biosynthesis, respiratory chain, amino acid
      synthesis, and the uncoupler). Culture supernatants were taken and analyzed for
      their "metabolic footprints" by using direct-injection mass spectrometry.
      Discriminant function analysis and hierarchical cluster analysis allowed these
      antifungal compounds to be distinguished and classified according to their modes
      of action. Genetic programming, a rule-evolving machine learning strategy,
      allowed respiratory inhibitors to be discriminated from others by using just two
      masses. Metabolic footprinting thus represents a rapid, convenient, and
      information-rich method for classifying the modes of action of antifungal
      substances.

PMID- 15466563
TI  - "Candidatus hepatoplasma crinochetorum," a new, stalk-forming lineage of
      Mollicutes colonizing the midgut glands of a terrestrial isopod.
AB  - Uncultivated bacteria that densely colonize the midgut glands (hepatopancreas) of
      the terrestrial isopod Porcellio scaber (Crustacea: Isopoda) were identified by
      cloning and sequencing of their 16S rRNA genes. Phylogenetic analysis revealed
      that these symbionts represent a novel lineage of the Mollicutes and are only
      distantly related (<82% sequence identity) to members of the Mycoplasmatales and
      Entomoplasmatales. Fluorescence in situ hybridization with a specific
      oligonucleotide probe confirmed that the amplified 16S rRNA gene sequences indeed
      originated from a homogeneous population of symbionts intimately associated with
      the epithelial surface of the hepatopancreas. The same probe also detected
      morphotypically identical symbionts in other crinochete isopods. Scanning and
      transmission electron microscopy revealed uniform spherical bacterial cells
      without a cell wall, sometimes interacting with the microvilli of the brush
      border by means of stalk-like cytoplasmic appendages, which also appeared to be
      involved in cell division through budding. Based on the isolated phylogenetic
      position and unique cytological properties, the provisional name "Candidatus
      Hepatoplasma crinochetorum" is proposed for this new taxon of Mollicutes
      colonizing the hepatopancreas of P. scaber.

PMID- 15466564
TI  - Quorum quenching: enzymatic disruption of N-acylhomoserine lactone-mediated
      bacterial communication in Burkholderia thailandensis.
AB  - Many species of gram-negative bacteria communicate by synthesizing, secreting,
      and responding to N-acylhomoserine lactones (AHLs), a mechanism termed quorum
      sensing. Several investigations have characterized numerous AHL-degrading enzymes
      (AiiA lactonases) encoded by environmental isolates of Bacillus spp. The
      Burkholderia thailandensis quorum system is comprised of at least three AHL
      synthases (AHSs) and five transcriptional regulators belonging to the LuxIR class
      of proteins. Expression of the Bacillus anthracis (Ames strain) AiiA lactonase in
      B. thailandensis completely abolished the accumulation of N-decanoylhomoserine
      lactone (C(10)-HSL) and N-octanoylhomoserine lactone (C(8)-HSL), reduced N
      hexanoylhomoserine lactone (C(6)-HSL) levels, altered both swarming and twitching
      motility, caused a significant increase in generation time, and affected carbon
      metabolism. In contrast, heterologous expression of the Bacillus cereus strain
      A24 AiiA lactonase in B. thailandensis reduced the concentrations of C(6)-HSL,
      C(8)-HSL, and C(10)-HSL to nondetectable levels; altered both swarming and
      twitching motility; and caused fluctuations in carbon utilization. Individual
      disruption of the B. thailandensis AHSs, specifically disruption of the btaI1 and
      btaI3 genes, which encode the proteins that direct the synthesis of C(8)-HSL and
      C(6)-HSL, respectively, caused the hyper-beta-hemolysis of sheep erythrocytes on
      blood agar plates. In contrast, AHL cleavage in B. thailandensis by the Bacillus
      AiiA lactonases failed to enhance beta-hemolytic activity. The results of this
      study demonstrate that heterologous expression of Bacillus sp. AiiA lactonases in
      B. thailandensis reduced AHL accumulation, affected both swarming and twitching
      motility, increased generation time, altered substrate utilization, and prevented
      the beta-hemolysis of sheep erythrocytes.

PMID- 15466565
TI  - Persistence of Streptococcus mutans in stationary-phase batch cultures and
      biofilms.
AB  - Streptococcus mutans is a member of oral plaque biofilms and is considered the
      major etiological agent of dental caries. We have characterized the survival of
      S. mutans strain UA159 in both batch cultures and biofilms. Bacteria grown in
      batch cultures in a chemically defined medium, FMC, containing an excess of
      glucose or sucrose caused the pH to decrease to 4.0 at the entry into stationary
      phase, and they survived for about 3 days. Survival was extended up to 11 days
      when the medium contained a limiting concentration of glucose or sucrose that was
      depleted by the time the bacteria reached stationary phase. Sugar-limited
      cultures maintained a pH of 7.0 throughout stationary phase. Their survival was
      shortened to 3 days by the addition of exogenous lactic acid at the entry into
      stationary phase. Sugar starvation did not lead to comparable survival in
      biofilms. Although the pH remained at 7.0, bacteria could no longer be cultured
      from biofilms 4 days after the imposition of glucose or sucrose starvation;
      BacLight staining results did not agree with survival results based on
      culturability. In both batch cultures and biofilms, survival could be extended by
      the addition of 0.5% mucin to the medium. Batch survival increased to an average
      of 26 (+/-8) days, and an average of 2.7 x 10(5) CFU per chamber were still
      present in biofilms that were starved of sucrose for 12 days.

PMID- 15466566
TI  - Stratified growth in Pseudomonas aeruginosa biofilms.
AB  - In this study, stratified patterns of protein synthesis and growth were
      demonstrated in Pseudomonas aeruginosa biofilms. Spatial patterns of protein
      synthetic activity inside biofilms were characterized by the use of two green
      fluorescent protein (GFP) reporter gene constructs. One construct carried an
      isopropyl-beta-d-thiogalactopyranoside (IPTG)-inducible gfpmut2 gene encoding a
      stable GFP. The second construct carried a GFP derivative, gfp-AGA, encoding an
      unstable GFP under the control of the growth-rate-dependent rrnBp(1) promoter.
      Both GFP reporters indicated that active protein synthesis was restricted to a
      narrow band in the part of the biofilm adjacent to the source of oxygen. The zone
      of active GFP expression was approximately 60 microm wide in colony biofilms and
      30 microm wide in flow cell biofilms. The region of the biofilm in which cells
      were capable of elongation was mapped by treating colony biofilms with
      carbenicillin, which blocks cell division, and then measuring individual cell
      lengths by transmission electron microscopy. Cell elongation was localized at the
      air interface of the biofilm. The heterogeneous anabolic patterns measured inside
      these biofilms were likely a result of oxygen limitation in the biofilm. Oxygen
      microelectrode measurements showed that oxygen only penetrated approximately 50
      microm into the biofilm. P. aeruginosa was incapable of anaerobic growth in the
      medium used for this investigation. These results show that while mature P.
      aeruginosa biofilms contain active, growing cells, they can also harbor large
      numbers of cells that are inactive and not growing.

PMID- 15466567
TI  - Characterization of the groEL and groES loci in Bifidobacterium breve UCC 2003:
      genetic, transcriptional, and phylogenetic analyses.
AB  - The bacterial heat shock response is characterized by the elevated expression of
      a number of chaperone complexes, including the GroEL and GroES proteins. The
      groES and groEL genes are highly conserved among eubacteria and are typically
      arranged as an operon. Genome analysis of Bifidobacterium breve UCC 2003 revealed
      that the groES and groEL genes are located in different chromosomal regions. The
      heat inducibility of the groEL and groES genes of B. breve UCC 2003 was verified
      by slot blot analysis. Northern blot analyses showed that the cspA gene is
      cotranscribed with the groEL gene, while the groES gene is transcribed as a
      monocistronic unit. The transcription initiation sites of these two mRNAs were
      determined by primer extension. Sequence and transcriptional analyses of the
      region flanking the groEL and groES genes of various bifidobacteria revealed
      similar groEL-cspA and groES gene units, suggesting a novel genetic organization
      of these chaperones. Phylogenetic analysis of the available bifidobacterial groES
      and groEL genes suggested that these genes evolved differently. Discrepancies in
      the phylogenetic positioning of groES-based trees make this gene an unreliable
      molecular marker. On the other hand, the bifidobacterial groEL gene sequences can
      be used as an alternative to current methods for tracing Bifidobacterium species,
      particularly because they allow a high level of discrimination between closely
      related species of this genus.

PMID- 15466568
TI  - Flow sorting of marine bacterioplankton after fluorescence in situ hybridization.
AB  - We describe an approach to sort cells from coastal North Sea bacterioplankton by
      flow cytometry after in situ hybridization with rRNA-targeted horseradish
      peroxidase-labeled oligonucleotide probes and catalyzed fluorescent reporter
      deposition (CARD-FISH). In a sample from spring 2003 >90% of the cells were
      detected by CARD-FISH with a bacterial probe (EUB338). Approximately 30% of the
      microbial assemblage was affiliated with the Cytophaga-Flavobacterium lineage of
      the Bacteroidetes (CFB group) (probe CF319a), and almost 10% was targeted by a
      probe for the beta-proteobacteria (probe BET42a). A protocol was optimized to
      detach cells hybridized with EUB338, BET42a, and CF319a from membrane filters
      (recovery rate, 70%) and to sort the cells by flow cytometry. The purity of
      sorted cells was >95%. 16S rRNA gene clone libraries were constructed from
      hybridized and sorted cells (S-EUB, S-BET, and S-CF libraries) and from
      unhybridized and unsorted cells (UNHYB library). Sequences related to the CFB
      group were significantly more frequent in the S-CF library (66%) than in the
      UNHYB library (13%). No enrichment of beta-proteobacterial sequence types was
      found in the S-BET library, but novel sequences related to Nitrosospira were
      found exclusively in this library. These bacteria, together with members of
      marine clade OM43, represented >90% of the beta-proteobacteria in the water
      sample, as determined by CARD-FISH with specific probes. This illustrates that a
      combination of CARD-FISH and flow sorting might be a powerful approach to study
      the diversity and potentially the activity and the genomes of different bacterial
      populations in aquatic habitats.

PMID- 15466569
TI  - Synchronous effects of temperature, hydrostatic pressure, and salinity on growth,
      phospholipid profiles, and protein patterns of four Halomonas species isolated
      from deep-sea hydrothermal-vent and sea surface environments.
AB  - Four strains of euryhaline bacteria belonging to the genus Halomonas were tested
      for their response to a range of temperatures (2, 13, and 30 degrees C),
      hydrostatic pressures (0.1, 7.5, 15, 25, 35, 45, and 55 MPa), and salinities (4,
      11, and 17% total salts). The isolates were psychrotolerant, halophilic to
      moderately halophilic, and piezotolerant, growing fastest at 30 degrees C, 0.1
      MPa, and 4% total salts. Little or no growth occurred at the highest hydrostatic
      pressures tested, an effect that was more pronounced with decreasing
      temperatures. Growth curves suggested that the Halomonas strains tested would
      grow well in cool to warm hydrothermal-vent and associated subseafloor habitats,
      but poorly or not at all under cold deep-sea conditions. The intermediate
      salinity tested enhanced growth under certain high-hydrostatic-pressure and low
      temperature conditions, highlighting a synergistic effect on growth for these
      combined stresses. Phospholipid profiles obtained at 30 degrees C indicated that
      hydrostatic pressure exerted the dominant control on the degree of lipid
      saturation, although elevated salinity slightly mitigated the increased degree of
      lipid unsaturation caused by increased hydrostatic pressure. Profiles of
      cytosolic and membrane proteins of Halomonas axialensis and H. hydrothermalis
      performed at 30 degrees C under various salinities and hydrostatic pressure
      conditions indicated several hydrostatic pressure and salinity effects, including
      proteins whose expression was induced by either an elevated salinity or
      hydrostatic pressure, but not by a combination of the two. The interplay between
      salinity and hydrostatic pressure on microbial growth and physiology suggests
      that adaptations to hydrostatic pressure and possibly other stresses may
      partially explain the euryhaline phenotype of members of the genus Halomonas
      living in deep-sea environments.

PMID- 15466570
TI  - Spatiotemporal distribution of marine magnetotactic bacteria in a seasonally
      stratified coastal salt pond.
AB  - The occurrence and distribution of magnetotactic bacteria (MB) were studied as a
      function of the physical and chemical conditions in meromictic Salt Pond,
      Falmouth, Mass., throughout summer 2002. Three dominant MB morphotypes were
      observed to occur within the chemocline. Small microaerophilic magnetite
      producing cocci were present at the top of the chemocline, while a greigite
      producing packet-forming bacterium occurred at the base of the chemocline. The
      distributions of these groups displayed sharp changes in abundance over small
      length scales within the water column as well as strong seasonal fluctuations in
      population abundance. We identified a novel, greigite-producing rod in the
      sulfidic hypolimnion that was present in relatively constant abundance over the
      course of the season. This rod is the first MB that appears to belong to the
      gamma-Proteobacteria, which may suggest an iron- rather than sulfur-based
      respiratory metabolism. Its distribution and phylogenetic identity suggest that
      an alternative model for the ecological and physiological role of magnetotaxis is
      needed for greigite-producing MB.

PMID- 15466571
TI  - Nonlegumes, legumes, and root nodules harbor different arbuscular mycorrhizal
      fungal communities.
AB  - Legumes are an important plant functional group since they can form a tripartite
      symbiosis with nitrogen-fixing Rhizobium bacteria and phosphorus-acquiring
      arbuscular mycorrhizal fungi (AMF). However, not much is known about AMF
      community composition in legumes and their root nodules. In this study, we
      analyzed the AMF community composition in the roots of three nonlegumes and in
      the roots and root nodules of three legumes growing in a natural dune grassland.
      We amplified a portion of the small-subunit ribosomal DNA and analyzed it by
      using restriction fragment length polymorphism and direct sequencing. We found
      differences in AMF communities between legumes and nonlegumes and between legume
      roots and root nodules. Different plant species also contained different AMF
      communities, with different AMF diversity. One AMF sequence type was much more
      abundant in legumes than in nonlegumes (39 and 13%, respectively). Root nodules
      contained characteristic AMF communities that were different from those in legume
      roots, even though the communities were similar in nodules from different legume
      species. One AMF sequence type was found almost exclusively in root nodules.
      Legumes and root nodules have relatively high nitrogen concentrations and high
      phosphorus demands. Accordingly, the presence of legume- and nodule-related AMF
      can be explained by the specific nutritional requirements of legumes or by host
      specific interactions among legumes, root nodules, and AMF. In summary, we found
      that AMF communities vary between plant functional groups (legumes and
      nonlegumes), between plant species, and between parts of a root system (roots and
      root nodules).

PMID- 15466573
TI  - Family shuffling of expandase genes to enhance substrate specificity for
      penicillin G.
AB  - Deacetoxycephalosporin C synthase (expandase) from Streptomyces clavuligerus,
      encoded by cefE, is an important industrial enzyme for the production of 7
      aminodeacetoxycephalosporanic acid from penicillin G. To improve the substrate
      specificity for penicillin G, eight cefE-homologous genes were directly evolved
      by using the DNA shuffling technique. After the first round of shuffling and
      screening, using an Escherichia coli ESS bioassay, four chimeras with higher
      activity were subjected to a second round. Subsequently, 20 clones were found
      with significantly enhanced activity. The kinetic parameters of two isolates that
      lack substrate inhibition showed 8.5- and 118-fold increases in the k(cat)/K(m)
      ratio compared to the S. clavuligerus expandase. The evolved enzyme with the 118
      fold increase is the most active obtained to date anywhere. Our shuffling results
      also indicate the remarkable plasticity of the expandase, suggesting that more
      active chimeras might be achievable with further rounds.

PMID- 15466572
TI  - Comparative analysis of physical maps of four Bacillus subtilis (natto) genomes.
AB  - The complete SfiI and I-CeuI physical maps of four Bacillus subtilis (natto)
      strains, which were previously isolated as natto (fermented soybean) starters,
      were constructed to elucidate the genome structure. Not only the similarity in
      genome size and organization but also the microheterogeneity of the gene context
      was revealed. No large-scale genome rearrangements among the four strains were
      indicated by mapping of the genes, including 10 rRNA operons (rrn) and relevant
      genes required for natto production, to the loci corresponding to those of the B.
      subtilis strain Marburg 168. However, restriction fragment length polymorphism
      and the presence or absence of strain-specific DNA sequences, such as the
      prophages SP beta, skin element, and PBSX, as well as the insertion element
      IS4Bsu1, could be used to identify one of these strains as a Marburg type and the
      other three strains as natto types. The genome structure and gene heterogeneity
      were also consistent with the type of indigenous plasmids harbored by the
      strains.

PMID- 15466574
TI  - Metabolically active eukaryotic communities in extremely acidic mine drainage.
AB  - Acid mine drainage (AMD) microbial communities contain microbial eukaryotes (both
      fungi and protists) that confer a biofilm structure and impact the abundance of
      bacteria and archaea and the community composition via grazing and other
      mechanisms. Since prokaryotes impact iron oxidation rates and thus regulate AMD
      generation rates, it is important to analyze the fungal and protistan
      populations. We utilized 18S rRNA and beta-tubulin gene phylogenies and
      fluorescent rRNA-specific probes to characterize the eukaryotic diversity and
      distribution in extremely acidic (pHs 0.8 to 1.38), warm (30 to 50 degrees C),
      metal-rich (up to 269 mM Fe(2+), 16.8 mM Zn, 8.5 mM As, and 4.1 mM Cu) AMD
      solutions from the Richmond Mine at Iron Mountain, Calif. A Rhodophyta (red
      algae) lineage and organisms from the Vahlkampfiidae family were identified. The
      fungal 18S rRNA and tubulin gene sequences formed two distinct phylogenetic
      groups associated with the classes Dothideomycetes and Eurotiomycetes. Three
      fungal isolates that were closely related to the Dothideomycetes clones were
      obtained. We suggest the name "Acidomyces richmondensis" for these isolates.
      Since these ascomycete fungi were morphologically indistinguishable, rRNA
      specific oligonucleotide probes were designed to target the Dothideomycetes and
      Eurotiomycetes via fluorescent in situ hybridization (FISH). FISH analyses
      indicated that Eurotiomycetes are generally more abundant than Dothideomycetes in
      all of the seven locations studied within the Richmond Mine system. This is the
      first study to combine the culture-independent detection of fungi with in situ
      detection and a demonstration of activity in an acidic environment. The results
      expand our understanding of the subsurface AMD microbial community structure.

PMID- 15466575
TI  - Bloom of filamentous bacteria in a mesotrophic lake: identity and potential
      controlling mechanism.
AB  - Ephemeral blooms of filamentous bacteria are a common phenomenon in the water
      column of oligo- to mesotrophic lakes. It is assumed that the appearance of such
      morphotypes is favored by selective predation of bacterivorous protists and that
      filter-feeding zooplankton plays a major role in suppressing these bacteria. The
      phylogenetic affiliation of the important bloom-forming filamentous bacteria in
      freshwaters is presently unknown. Here we report the identification of dominant
      members of a filamentous bacterial assemblage during a bloom of such morphotypes
      in a mesotrophic lake. By molecular cloning and fluorescence in situ
      hybridization with specific oligonucleotide probes, up to 98% of filamentous
      cells in lake water could be assigned to a clade of almost identical (99%
      similarity) 16S rRNA gene sequence types, the cosmopolitan freshwater LD2
      cluster. For a period of less than 1 week, members of the LD2 clade constituted
      >40% of the total bacterial biomass, potentially favored by high grazing of
      planktivorous protists. This is probably the most pronounced case of dominance by
      a single bacterioplankton species ever observed in natural freshwaters. In
      enclosures artificially stocked with the metazoan filter feeder Daphnia, bacteria
      related to the LD2 clade formed a significantly larger fraction of filaments than
      in enclosures where Daphnia had been removed. However, in the presence of higher
      numbers of Daphnia individuals, the LD2 bacteria, like other filaments, were
      eventually eliminated both in enclosures and in the lake. This points at the
      potential importance of filter-feeding zooplankton in controlling the occurrence
      and species composition of filamentous bacterial morphotypes in freshwater
      plankton.

PMID- 15466576
TI  - Abundance of reverse tricarboxylic acid cycle genes in free-living microorganisms
      at deep-sea hydrothermal vents.
AB  - Since the discovery of hydrothermal vents more than 25 years ago, the Calvin
      Bassham-Benson (Calvin) cycle has been considered the principal carbon fixation
      pathway in this microbe-based ecosystem. However, on the basis of recent
      molecular data of cultured free-living and noncultured episymbiotic members of
      the epsilon subdivision of Proteobacteria and earlier carbon isotope data of
      primary consumers, an alternative autotrophic pathway may predominate. Here,
      genetic and culture-based approaches demonstrated the abundance of reverse
      tricarboxylic acid cycle genes compared to the abundance of Calvin cycle genes in
      microbial communities from two geographically distinct deep-sea hydrothermal
      vents. PCR with degenerate primers for three key genes in the reverse
      tricarboxylic acid cycle and form I and form II of ribulose 1,5-bisphosphate
      carboxylase/oxygenase (Calvin cycle marker gene) were utilized to demonstrate the
      abundance of the reverse tricarboxylic acid cycle genes in diverse vent samples.
      These genes were also expressed in at least one chimney sample. Diversity,
      similarity matrix, and phylogenetic analyses of cloned samples and amplified gene
      products from autotrophic enrichment cultures suggest that the majority of
      autotrophs that utilize the reverse tricarboxylic acid cycle are members of the
      epsilon subdivision of Proteobacteria. These results parallel the results of
      previously published molecular surveys of 16S rRNA genes, demonstrating the
      dominance of members of the epsilon subdivision of Proteobacteria in free-living
      hydrothermal vent communities. Members of the epsilon subdivision of
      Proteobacteria are also ubiquitous in many other microaerophilic to anaerobic
      sulfidic environments, such as the deep subsurface. Therefore, the reverse
      tricarboxylic acid cycle may be a major autotrophic pathway in these environments
      and significantly contribute to global autotrophic processes.

PMID- 15466577
TI  - Molecular characterization of two lactate dehydrogenase genes with a novel
      structural organization on the genome of Lactobacillus sp. strain MONT4.
AB  - Two lactate dehydrogenase (ldh) genes from Lactobacillus sp. strain MONT4 were
      cloned by complementation in Escherichia coli DC1368 (ldh pfl) and were
      sequenced. The sequence analysis revealed a novel genomic organization of the ldh
      genes. Subcloning of the individual ldh genes and their Northern blot analyses
      indicated that the genes are monocistronic.

PMID- 15466578
TI  - Aquatic snails, passive hosts of Mycobacterium ulcerans.
AB  - Accumulative indirect evidence of the epidemiology of Mycobacterium ulcerans
      infections causing chronic skin ulcers (i.e., Buruli ulcer disease) suggests that
      the development of this pathogen and its transmission to humans are related
      predominantly to aquatic environments. We report that snails could transitorily
      harbor M. ulcerans without offering favorable conditions for its growth and
      replication. A novel intermediate link in the transmission chain of M. ulcerans
      becomes likely with predator aquatic insects in addition to phytophage insects.
      Water bugs, such as Naucoris cimicoides, a potential vector of M. ulcerans, were
      shown to be infected specifically by this bacterium after feeding on snails
      experimentally exposed to M. ulcerans.

PMID- 15466579
TI  - Rapid quantitative detection of Listeria monocytogenes in meat products by real
      time PCR.
AB  - We describe a quick and simple method for the quantitative detection of Listeria
      monocytogenes in meat products. This method is based on filtration, Chelex-100
      based DNA purification, and real-time PCR. It can detect as few as 100 CFU/g and
      quantify as few as 1,000 CFU/g, with excellent accuracy compared to that of the
      plate count method. Therefore, it is a promising alternative for the detection of
      L. monocytogenes in meat products.

PMID- 15466581
TI  - Intestinal mucus alters the ability of probiotic bacteria to bind aflatoxin B1 in
      vitro.
AB  - Several probiotics are known to bind aflatoxin B(1) (AFB(1)) to their surfaces
      and to adhere to intestinal mucus. In this study, preincubation of two probiotic
      preparations with either AFB(1) or mucus reduced the subsequent surface binding
      of mucus and AFB(1), respectively, in a strain-dependent manner.

PMID- 15466580
TI  - Role of Hippoboscidae flies as potential vectors of Bartonella spp. infecting
      wild and domestic ruminants.
AB  - The putative role of biting flies in Bartonella transmission among ruminants was
      investigated. Amplification of the Bartonella citrate synthase gene from 83
      Hippoboscidae was detected in 94% of 48 adult Lipoptena cervi flies, 71% of 17
      adult Hippobosca equina flies, 100% of 20 adult Melophagus ovinus flies, and 100%
      of 10 M. ovinus pupae. Our findings suggest that Hippoboscidae play a role in the
      transmission of Bartonella among ruminants. The vertical transmission of
      Bartonella in M. ovinus and the presence of Bartonella DNA in all samples suggest
      a symbiotic association between Bartonella and M. ovinus.

PMID- 15466582
TI  - Genetic typing of shiga toxin 2 variants of Escherichia coli by PCR-restriction
      fragment length polymorphism analysis.
AB  - Shiga toxins Stx1 and Stx2 play a prominent role in the pathogenesis of Shiga
      toxin-producing Escherichia coli (STEC) infections. Several variants of the
      stx(2) gene, encoding Stx2, have been described. In this study, we developed a
      PCR-restriction fragment length polymorphism system for typing stx(2) genes of
      STEC strains. The typing system discriminates eight described variants and allows
      the identification of new stx(2) variants and STEC isolates carrying multiple
      stx(2) genes. A phylogenetic tree, based on the nucleotide sequences of the toxin
      encoding genes, demonstrates that stx(2) sequences with the same PvuII HaeIII
      HincII AccI type generally cluster together.

PMID- 15466583
TI  - Metabolism of 2-mercaptobenzothiazole by Rhodococcus rhodochrous.
AB  - 2-Mercaptobenzothiazole, which is mainly used in the rubber industry as a
      vulcanization accelerator, is very toxic and is considered to be recalcitrant. We
      show here for the first time that it can be biotransformed and partially
      mineralized by a pure-culture bacterial strain of Rhodococcus rhodochrous. Three
      metabolites, among four detected, were identified.

PMID- 15466584
TI  - Repressor mutant forms of the Azospirillum brasilense NtrC protein.
AB  - The Azospirillum brasilense mutant strains FP8 and FP9, after treatment with
      nitrosoguanidine, showed a null Nif phenotype and were unable to use nitrate as
      their sole nitrogen source. Sequencing of the ntrC genes revealed single
      nucleotide mutations in the NtrC nucleotide-binding site. The phenotypes of these
      strains are discussed in relation to their genotypes.

PMID- 15466585
TI  - A single amino acid substitution converts gamma-glutamyltranspeptidase to a class
      IV cephalosporin acylase (glutaryl-7-aminocephalosporanic acid acylase).
AB  - The aspartyl residue at position 433 of gamma-glutamyltranspeptidase of
      Escherichia coli K-12 was replaced by an asparaginyl residue. This substitution
      enabled gamma-glutamyltranspeptidase to deacylate glutaryl-7-aminocephalosporanic
      acid, producing 7-aminocephalosporanic acid, which is a starting material for the
      synthesis of semisynthetic cephalosporins.

PMID- 15466586
TI  - Reverse transcription-booster PCR for detection of noroviruses in shellfish.
AB  - The methods commonly used for norovirus (NV) detection are based on reverse
      transcription-PCR (RT-PCR) followed by confirmation of the amplified sequence. To
      increase sensitivity, an RT-booster PCR was developed. The proposed method showed
      an increase in sensitivity at least 2 log units for all the NV strains tested
      compared with the standard RT-PCR method. Higher sensitivity was confirmed in
      tests on experimentally and naturally contaminated shellfish.

PMID- 15466587
TI  - Stabilization of oil-water emulsions by hydrophobic bacteria.
AB  - Formation of oil-water emulsions during bacterial growth on hydrocarbons is often
      attributed to biosurfactants. Here we report the ability of certain intact
      bacterial cells to stabilize oil-in-water and water-in-oil emulsions without
      changing the interfacial tension, by inhibition of droplet coalescence as
      observed in emulsion stabilization by solid particles like silica.

PMID- 15466588
TI  - Cloning and expression of clt genes encoding milk-clotting proteases from
      Myxococcus xanthus 422.
AB  - The screening of a gene library of the milk-clotting strain Myxococcus xanthus
      422 constructed in Escherichia coli allowed the description of eight positive
      clones containing 26 open reading frames. Only three of them (cltA, cltB, and
      cltC) encoded proteins that exhibited intracellular milk-clotting ability in E.
      coli, Saccharomyces cerevisiae, and Pichia pastoris expression systems.

PMID- 15466589
TI  - Isolation of lightning-competent soil bacteria.
AB  - Artificial transformation is typically performed in the laboratory by using
      either a chemical (CaCl(2)) or an electrical (electroporation) method. However,
      laboratory-scale lightning has been shown recently to electrotransform
      Escherichia coli strain DH10B in soil. In this paper, we report on the isolation
      of two "lightning-competent" soil bacteria after direct electroporation of the
      Nycodenz bacterial ring extracted from prairie soil in the presence of the
      pBHCRec plasmid (Tc(r), Sp(r), Sm(r)). The electrotransformability of the
      isolated bacteria was measured both in vitro (by electroporation cuvette) and in
      situ (by lightning in soil microcosm) and then compared to those of E. coli DH10B
      and Pseudomonas fluorescens C7R12. The electrotransformation frequencies measured
      reached 10(-3) to 10(-4) by electroporation and 10(-4) to 10(-5) by simulated
      lightning, while no transformation was observed in the absence of electrical
      current. Two of the isolated lightning-competent soil bacteria were identified as
      Pseudomonas sp. strains.

PMID- 15466590
TI  - Genetic identification of a putative vinyl chloride reductase in Dehalococcoides
      sp. strain BAV1.
AB  - Dehalococcoides sp. strain BAV1 couples growth with the reductive dechlorination
      of vinyl chloride (VC) to ethene. Degenerate primers targeting conserved regions
      in reductive dehalogenase (RDase) genes were designed and used to PCR amplify
      putative RDase genes from strain BAV1. Seven unique RDase gene fragments were
      identified. Transcription analysis of VC-grown BAV1 cultures suggested that bvcA
      was involved in VC reductive dechlorination, and the complete sequence of bvcA
      was obtained. bvcA was absent in Dehalococcoides isolates that failed to respire
      VC, yet was detected in four of eight VC-respiring mixed cultures.

PMID- 15466591
TI  - Camptothecin enhances the frequency of oligonucleotide-directed gene repair in
      mammalian cells by inducing DNA damage and activating homologous recombination.
AB  - Camptothecin (CPT) is an anticancer drug that promotes DNA breakage at
      replication forks and the formation of lesions that activate the processes of
      homologous recombination (HR) and nonhomologous end joining. We have taken
      advantage of the CPT-induced damage response by coupling it to gene repair
      directed by synthetic oligonucleotides, a process in which a mutant base pair is
      converted into a wild-type one. Here, we show that pretreating DLD-1 cells with
      CPT leads to a significant stimulation in the frequency of correction of an
      integrated mutant enhanced green fluorescent protein gene. The stimulation is
      dose-dependent and coincident with the formation of double-strand DNA breaks.
      Caffeine, but not vanillin, blocks the enhancement of gene repair suggesting
      that, in this system, HR is the pathway most responsible for elevating the
      frequency of correction. The involvement of HR is further proven by studies in
      which wortmannin was seen to inhibit gene repair at high concentrations but not
      at lower levels that are known to inhibit DNA-PK activity. Taken together, our
      results suggest that DNA damage induced by CPT activates a cellular response that
      stimulates gene repair in mammalian cells.

PMID- 15466592
TI  - DNA double strand break repair in human bladder cancer is error prone and
      involves microhomology-associated end-joining.
AB  - In human cells DNA double strand breaks (DSBs) can be repaired by the non
      homologous end-joining (NHEJ) pathway. In a background of NHEJ deficiency, DSBs
      with mismatched ends can be joined by an error-prone mechanism involving joining
      between regions of nucleotide microhomology. The majority of joins formed from a
      DSB with partially incompatible 3' overhangs by cell-free extracts from human
      glioblastoma (MO59K) and urothelial (NHU) cell lines were accurate and produced
      by the overlap/fill-in of mismatched termini by NHEJ. However, repair of DSBs by
      extracts using tissue from four high-grade bladder carcinomas resulted in no
      accurate join formation. Junctions were formed by the non-random deletion of
      terminal nucleotides and showed a preference for annealing at a microhomology of
      8 nt buried within the DNA substrate; this process was not dependent on
      functional Ku70, DNA-PK or XRCC4. Junctions were repaired in the same manner in
      MO59K extracts in which accurate NHEJ was inactivated by inhibition of Ku70 or
      DNA-PK(cs). These data indicate that bladder tumour extracts are unable to
      perform accurate NHEJ such that error-prone joining predominates. Therefore, in
      high-grade tumours mismatched DSBs are repaired by a highly mutagenic,
      microhomology-mediated, alternative end-joining pathway, a process that may
      contribute to genomic instability observed in bladder cancer.

PMID- 15466593
TI  - Comparative genomics of the FtsK-HerA superfamily of pumping ATPases:
      implications for the origins of chromosome segregation, cell division and viral
      capsid packaging.
AB  - Recently, it has been shown that a predicted P-loop ATPase (the HerA or MlaA
      protein), which is highly conserved in archaea and also present in many bacteria
      but absent in eukaryotes, has a bidirectional helicase activity and forms
      hexameric rings similar to those described for the TrwB ATPase. In this study,
      the FtsK-HerA superfamily of P-loop ATPases, in which the HerA clade comprises
      one of the major branches, is analyzed in detail. We show that, in addition to
      the FtsK and HerA clades, this superfamily includes several families of
      characterized or predicted ATPases which are predominantly involved in extrusion
      of DNA and peptides through membrane pores. The DNA-packaging ATPases of various
      bacteriophages and eukaryotic double-stranded DNA viruses also belong to the FtsK
      HerA superfamily. The FtsK protein is the essential bacterial ATPase that is
      responsible for the correct segregation of daughter chromosomes during cell
      division. The structural and evolutionary relationship between HerA and FtsK and
      the nearly perfect complementarity of their phyletic distributions suggest that
      HerA similarly mediates DNA pumping into the progeny cells during archaeal cell
      division. It appears likely that the HerA and FtsK families diverged
      concomitantly with the archaeal-bacterial division and that the last universal
      common ancestor of modern life forms had an ancestral DNA-pumping ATPase that
      gave rise to these families. Furthermore, the relationship of these cellular
      proteins with the packaging ATPases of diverse DNA viruses suggests that a common
      DNA pumping mechanism might be operational in both cellular and viral genome
      segregation. The herA gene forms a highly conserved operon with the gene for the
      NurA nuclease and, in many archaea, also with the orthologs of eukaryotic double
      strand break repair proteins MRE11 and Rad50. HerA is predicted to function in a
      complex with these proteins in DNA pumping and repair of double-stranded breaks
      introduced during this process and, possibly, also during DNA replication.
      Extensive comparative analysis of the 'genomic context' combined with in-depth
      sequence analysis led to the prediction of numerous previously unnoticed
      nucleases of the NurA superfamily, including a specific version that is likely to
      be the endonuclease component of a novel restriction-modification system. This
      analysis also led to the identification of previously uncharacterized nucleases,
      such as a novel predicted nuclease of the Sir2-type Rossmann fold, and
      phosphatases of the HAD superfamily that are likely to function as partners of
      the FtsK-HerA superfamily ATPases.

PMID- 15466594
TI  - Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-1/TR3 and
      nuclear factor-kappaB.
AB  - The effect of orphan nuclear receptor Nur77 overexpression on activation of an
      interleukin-2 (IL-2) promoter-luciferase construct was analyzed in the human
      leukemic cell line Jurkat. Cotransfection of the IL-2 promoter construct together
      with the Nur77 expression plasmid resulted in a significant repression of IL-2
      promoter activation compared to control cells. The repression by Nur77 requires
      the N-terminal activation function-1 domain. The repressive effect of Nur77 on IL
      2 promoter activation is mediated through inhibition of the transcription factor
      complex nuclear factor-kappaB (NF-kappaB), since blocking or alteration of the IL
      2 NF-kappaB binding sites resulted in abrogation of the repressive effect of
      Nur77. Moreover, further examination of a reporter gene construct containing
      multiple copies of the IL-2 CD28 response element (CD28RE) showed that Nur77 can
      inhibit transactivation mediated by the NF-kappaB components p65 and c-Rel.
      However, no effect of Nur77 was seen on p65-mediated transactivation of a
      construct containing multiple NF-kappaB binding sites of the HIV LTR. Our data
      suggest that Nur77 is able to block activation through NF-kappaB when bound to
      low-affinity NF-kappaB binding sites, such as those located in the IL-2 promoter.

PMID- 15466595
TI  - Mutational analysis of the damage-recognition and catalytic mechanism of human
      SMUG1 DNA glycosylase.
AB  - Single-strand selective monofunctional uracil-DNA glycosylase (SMUG1), previously
      thought to be a backup enzyme for uracil-DNA glycosylase, has recently been shown
      to excise 5-hydroxyuracil (hoU), 5-hydroxymethyluracil (hmU) and 5-formyluracil
      (fU) bearing an oxidized group at ring C5 as well as an uracil. In the present
      study, we used site-directed mutagenesis to construct a series of mutants of
      human SMUG1 (hSMUG1), and tested their activity for uracil, hoU, hmU, fU and
      other bases to elucidate the catalytic and damage-recognition mechanism of
      hSMUG1. The functional analysis of the mutants, together with the homology
      modeling of the hSMUG1 structure based on that determined recently for Xenopus
      laevis SMUG1, revealed the crucial residues for the rupture of the N-glycosidic
      bond (Asn85 and His239), discrimination of pyrimidine rings through pi-pi
      stacking to the base (Phe98) and specific hydrogen bonds to the Watson-Crick face
      of the base (Asn163) and exquisite recognition of the C5 substituent through
      water-bridged (uracil) or direct (hoU, hmU and fU) hydrogen bonds (Gly87-Met91).
      Integration of the present results and the structural data elucidates how hSMUG1
      accepts uracil, hoU, hmU and fU as substrates, but not other oxidized pyrimidines
      such as 5-hydroxycytosine, 5-formylcytosine and thymine glycol, and intact
      pyrimidines such as thymine and cytosine.

PMID- 15466596
TI  - A novel GTPase activated by the small subunit of ribosome.
AB  - The GTPase activity of Escherichia coli YjeQ, here named RsgA (ribosome small
      subunit-dependent GTPase A), has been shown to be significantly enhanced by
      ribosome or its small subunit. The enhancement of GTPase activity was inhibited
      by several aminoglycosides bound at the A site of the small subunit, but not by a
      P site-specific antibiotic. RsgA stably bound the small subunit in the presence
      of GDPNP, but not in the presence of GTP or GDP, to dissociate ribosome into
      subunits. Disruption of the gene for RsgA from the genome affected the growth of
      the cells, which predominantly contained the dissociated subunits having only a
      weak activation activity of RsgA. We also found that 17S RNA, a putative
      precursor of 16S rRNA, was contained in the small subunit of the ribosome from
      the RsgA-deletion strain. RsgA is a novel GTPase that might provide a new insight
      into the function of ribosome.

PMID- 15466597
TI  - Automated synthesis of new ferrocenyl-modified oligonucleotides: study of their
      properties in solution.
AB  - We have developed new ferrocenyl-modified oligonucleotide (ODN) probes for
      electrochemical DNA sensors. A monofunctional ferrocene containing
      phosphoramidite group has been prepared, and a new bisfunctional ferrocene
      containing phosphoramidite and dimethoxytrityl (DMT) groups has been developed.
      These ferrocenyl-phosphoramidites have been directly employed in an automated
      solid-phase DNA synthesizer using phosphoramidite chemistry. The advantages of
      this method are that it allows a non-specialist in nucleotide chemistry to access
      labeled ODNs and that it has demonstrated good results. ODNs modified at the 3'
      and/or 5' extremities have been prepared, with the incorporation of the
      ferrocenyl group into the chain. The 5' position appears to be more important due
      to its particular behavior. The thermal stability and electrochemical properties
      of these new ODN ferrocenes were analyzed before and after hybridization with
      different ODNs. The feasibility of using these new ferrocenyl-labeled ODNs in DNA
      sensors has been demonstrated.

PMID- 15466598
TI  - Attachment styles and contingencies of self-worth.
AB  - Previous research on attachment theory has focused on mean differences in level
      of self-esteem among people with different attachment styles. The present study
      examines the associations between attachment styles and different bases of self
      esteem, or contingencies of self-worth, among a sample of 795 college students.
      Results showed that attachment security was related to basing self-worth on
      family support. Both the preoccupied attachment style and fearful attachment
      style were related to basing self-worth on physical attractiveness. The
      dismissing attachment style was related to basing self-worth less on others'
      approval, family support, and God's love.

PMID- 15466599
TI  - How are sociosexuality, sex drive, and lifetime number of sexual partners
      related?
AB  - In two studies (ns = 277 and 221), the authors examined the relationships among
      sex drive, sociosexuality, lifetime number of sex partners, and gender identity.
      They found that sex drive is highly and positively correlated with sociosexual
      orientation, and that both sex drive and sociosexual orientation are positively
      correlated with lifetime number of sex partners. However, partial correlations
      revealed that sociosexual orientation is an independent predictor of lifetime
      number of sex partners, whereas sex drive is not. The authors were also able to
      replicate and extend Mikach and Bailey's (1999) finding that gender identity is
      related to women's lifetime number of sex partners. More masculine women had more
      sex partners and had a less restricted sociosexual orientation than did less
      masculine women; less masculine men had a higher sex drive than did more
      masculine men. The findings are discussed with regard to theory and research on
      sex drive and sociosexuality.

PMID- 15466600
TI  - Tracking the timecourse of social perception: the effects of racial cues on event
      related brain potentials.
AB  - Event-related potentials were used to track social perception processes
      associated with viewing faces of racial ingroup and outgroup members. Activity
      associated with three distinct processes was detected. First, peaking at
      approximately 170 ms, faces were distinguished from nonface stimuli. Second,
      peaking at approximately 250 ms, ingroup members were differentiated from
      outgroup members, with a larger component suggesting greater attention to ingroup
      members. This effect may reflect the spontaneous application of a deeper level of
      processing to ingroup members. Third, peaking at approximately 520 ms, evaluative
      differentiation of ingroup and outgroup members occurred, with greater ingroup
      bias displayed by those with higher levels of prejudice on an explicit measure.
      Together, the results demonstrate the promise of using neural processes to track
      the presence, timing, and degree of activation of components relevant to social
      perception, prejudice, and stereotyping.

PMID- 15466601
TI  - Predicting attitude extremity: the interactive effects of schema development and
      the need to evaluate and their mediation by evaluative integration.
AB  - Research on attitude extremity suggests that schemas containing more information
      about a particular attitude domain are more likely to be associated with extreme
      attitudes toward objects in that domain when perceivers' responses toward
      features of the domain are evaluatively integrated. The present study argues that
      a high need to evaluate may play an important role in determining when schema
      development will be associated with the integrated responses to different domain
      features necessary for extremity. Consistent with this argument, data from a
      nationally representative survey of political attitudes indicated that the need
      to evaluate was associated with increased extremity across two different indices
      of the latter; that it moderated the relationships between schema development (in
      the form of political expertise), on one hand, and increased extremity and
      integration, on the other; and that the moderating effects of the need to
      evaluate vis-a-vis extremity were mediated by integration.

PMID- 15466603
TI  - Effects of the activation of affective information on stereotyping: when sadness
      increases stereotype use.
AB  - Two studies explored the impact of mere activation of affective information on
      the use of stereotypes in social judgment. These studies provided consistent
      results showing that the activation of information related to sadness increases
      reliance on stereotypes, whereas the activation of information related to
      happiness decreases it. These results were obtained in the absence of affective
      state changes among the participants and with the use of two different priming
      procedures (Study 1: scrambled sentences, Study 2: subliminal priming) and two
      different judgment tasks (Study 1: impression formation, Study 2: guilt
      judgment). Complementing the informational view of affective states, it is
      suggested that affective information of which people are not conscious activates
      behavioral tendencies of approach or of avoidance associated with the related
      emotion.

PMID- 15466602
TI  - Social norms and identity relevance: a motivational approach to normative
      behavior.
AB  - Two studies demonstrated that greater identification with a group was associated
      with more positive emotions for members who conformed with versus violated the
      group's norms. These effects were found with injunctive norms, which specify what
      members should do or what they ideally would do, but emerged less consistently
      with descriptive norms, which specify what members typically do. Descriptive
      norms affected emotional responses when they acquired identity-relevance by
      differentiating an important ingroup from a rival outgroup. For these descriptive
      norms, much like injunctive norms, greater identification yielded more positive
      emotions following conformity than violation. The authors suggest that positive
      emotions and self-evaluations underlie conformity with the norms of self-defining
      groups.

PMID- 15466604
TI  - The swimsuit becomes us all: ethnicity, gender, and vulnerability to self
      objectification.
AB  - Self-objectification theory posits and past research has found that Caucasian
      women's body image is negatively affected by a stigma of obesity and
      sociocultural norm of thinness that leads women to self-focus from a critical
      external perspective. However, research in this area is limited by its
      methodology and the restricted demographic composition of its study participants.
      The current study tested 176 men and 224 women of Caucasian, African American,
      Hispanic, and Asian American descent in a situation that induced a state of self
      objectification (e.g., wearing a one-piece Speedo bathing suit) or that served as
      a control condition (e.g., wearing a sweater). Contrary to previous research,
      when put in a self-objectifying situation, men and women of every ethnicity
      experienced negative outcomes (e.g., lower math performance) that parallel those
      previously found for Caucasian women.

PMID- 15466605
TI  - Implicit and explicit ethnocentrism: revisiting the ideologies of prejudice.
AB  - Two studies investigated relationships among individual differences in implicit
      and explicit prejudice, right-wing ideology, and rigidity in thinking. The first
      study examined these relationships focusing on White Americans' prejudice toward
      Black Americans. The second study provided the first test of implicit
      ethnocentrism and its relationship to explicit ethnocentrism by studying the
      relationship between attitudes toward five social groups. Factor analyses found
      support for both implicit and explicit ethnocentrism. In both studies, mean
      explicit attitudes toward out groups were positive, whereas implicit attitudes
      were negative, suggesting that implicit and explicit prejudices are distinct;
      however, in both studies, implicit and explicit attitudes were related (r = .37,
      .47). Latent variable modeling indicates a simple structure within this
      ethnocentric system, with variables organized in order of specificity. These
      results lead to the conclusion that (a) implicit ethnocentrism exists and (b) it
      is related to and distinct from explicit ethnocentrism.

PMID- 15466606
TI  - A time to tan: proximal and distal effects of mortality salience on sun exposure
      intentions.
AB  - According to the dual defense model of terror management, proximal defenses are
      engaged to reduce the conscious impact of mortality salience, whereas thoughts of
      death outside of conscious awareness motivate distal defenses aimed at
      maintaining self-esteem. Two experiments examined these ideas by assessing
      women's intentions to engage in tanning-related behavior. In Study 1, when
      concerns about death (relative to dental pain) were in focal attention,
      participants increased intentions to protect themselves from dangerous sun
      exposure. In contrast, when thoughts about death were outside of focal attention,
      participants decreased interest in sun protection. In Study 2, participants
      primed to associate tanned skin with an attractive appearance responded to
      mortality concerns outside of focal attention with increased interest in tanning
      products and services. These findings are discussed in relation to the dual
      defense model of terror management, societal determinants of self-esteem, and
      implications for health risk and promotion.

PMID- 15466607
TI  - All our troubles seem so far away: temporal pattern to accessible alternatives
      and retrospective team appraisals.
AB  - Three studies tested the hypothesis that thoughts about alternatives become
      increasingly accessible over time, leading poor outcomes to feel subjectively
      farther away and less inevitable. This subjective temporal distance bias was
      obtained even though actual time since poor and good outcomes was identical. In
      Study 1, participants who recalled distant poor team outcomes thought of
      alternatives easily and outcomes felt farther away and less inevitable. Thoughts
      about outcomes were most easily accessible after good outcomes, which felt closer
      and more inevitable. In Study 2, with measures obtained immediately or at a later
      time on a negotiation task, changes over time occurred primarily for poor team
      outcomes. In Study 3, team performance on an investment task indicated it is
      whether alternatives are thought of easily, not thought content, that produces
      this effect. Discussion centers on temporal appraisals, other temporal biases,
      and teams.

PMID- 15466609
TI  - Exercise self-efficacy, enjoyment, and feeling states among adolescents.
AB  - Knowledge of cognitions and feelings related to physical activity (PA) can assist
      in counseling adolescents to prevent the decrease in PA that occurs during this
      developmental period. This study, which involves a 2 (gender) 2 (race) 3
      (developmental stage) design, examines relationships among PA self-efficacy (SE),
      enjoyment, and feeling states (FS) during PA and compares responses among 168
      African American and European American boys and girls during early, middle, and
      late adolescence. More positive FS during a standardized PA episode on a
      treadmill predicts higher postactivity SE and greater enjoyment of the task. FS
      worsens as the session progresses, particularly for adolescents who in early
      puberty, report feeling significantly worse than those in both middle and late
      puberty at 16 minutes and 20 minutes. Findings suggest that nurses should assist
      adolescents to reduce negative feelings during activity to augment PA enjoyment,
      as well as SE following PA.

PMID- 15466610
TI  - Nurses' knowledge of traditional Chinese postpartum customs.
AB  - This study was conducted to determine nurses' and postpartum women's knowledge of
      and attitudes toward the traditional Chinese custom of 1-month confinement
      following delivery, to discover factors influencing the attitudes, and to analyze
      the correlation between them. After a descriptive and inferential analysis of 173
      questionnaires (121 recent mothers and 52 nurses), a significant difference was
      found in the women's and nurses' scores for knowledge of the postpartum
      confinement custom, with postpartum women scoring higher than the nursing staff
      on average. Both groups held positive attitudes toward the traditional custom.
      Attitudes and level of knowledge were positively correlated. Results of this
      study can serve as a reference for in-service nursing education, which should
      include information about traditional postpartum customs.

PMID- 15466611
TI  - Pain assessment practices with nursing home residents.
AB  - The purpose of this research was to describe the kinds of pain assessments
      nursing home staff use with nursing home residents and the characteristics and
      behaviors of residents that staff consider as they assess pain. Twenty-one focus
      groups were held in 12 nursing homes. Nurses and other nursing home staff
      attended the focus groups. Coding techniques consistent with ethnographic
      methodology were used for data analysis. Four themes identified an underlying
      uncertainty in assessing residents' pain, the staff relationship-centered
      approach to pain assessment, the resident cues that alert staff to pain, and
      residents' characteristics important to the nursing assessment. Composition of
      focus groups made a difference in participation of certified nursing assistants
      in focus group discussion. Urban and rural differences were noted across the
      focus groups. Research is needed to further refine pain assessment techniques
      specifically for nursing home settings.

PMID- 15466612
TI  - Assessment of patient pain in the postoperative context.
AB  - Because of its subjective nature, the assessment of pain requires the use of
      comprehensive practices that accurately reflect a patient's experiences of pain.
      The purpose of this study was to determine how nurses make decisions in their
      assessment of patients' pain in the postoperative clinical setting. An
      observational design was chosen as the means of examining pain activities in two
      surgical units of a metropolitan teaching hospital in Melbourne, Australia. Six
      fixed observation times were selected. Each 2-hour observation period was
      examined 12 times thus resulting in 74 observations. In total, 316 pain
      activities were determined. Five themes relating to assessment were identified
      from the data analysis: simple questioning, use of a pain scale, complex
      assessment, the lack of pain assessment, and physical examination for pain. The
      study identified how nurses' prioritization of work demands created barriers in
      conducting timely and comprehensive pain assessment decisions.

PMID- 15466613
TI  - Uncertainty and its antecedents in patients with atrial fibrillation.
AB  - The aim of this descriptive, correlational, and cross-sectional survey was to
      explore uncertainty in patients with atrial fibrillation and to examine the
      relationships between uncertainty and its antecedents, including education,
      social support, and perceived seriousness of illness in patients newly diagnosed
      with atrial fibrillation. The theoretical framework of the study was Mishel's
      middle-range nursing theory of uncertainty in illness. A convenience sample of 81
      participants recruited from two academic medical centers over 10 months was
      interviewed. Uncertainty was moderately high in patients with atrial fibrillation
      compared to other clinical populations. Among antecedents of uncertainty, higher
      education was significantly associated with less uncertainty (beta = -.21 to 
      .25). Except for tangible support, persons with greater social supports perceived
      less uncertainty (beta= -.25 to -.27), and individuals with greater perceived
      seriousness of illness reported greater uncertainty (beta= .30 to .33).

PMID- 15466614
TI  - Knowledge, attitudes, and predictors of advance directive discussions of
      registered nurses.
AB  - The purpose of this study was to describe nurses' knowledge, attitudes, and
      experiences regarding advance directives. A secondary purpose was to examine
      predictors of advance directive discussions between nurses and patients. Seven
      hundred and nineteen respondents, randomly selected from a list of registered
      nurses in the state of Ohio, completed mailed questionnaires. Descriptive t test,
      chi-square, and logistic regression statistics were used in the data analyses.
      The respondents were knowledgeable and possessed positive attitudes about advance
      directives. Higher self-perceived confidence in advance directive discussion
      skills and the experience of caring for at least one patient with a current
      advance directive were found to be significant predictors of advance directive
      discussions. These findings suggest that experience with advance directives
      documents is critical for nurses' comfort and that developing interventions to
      further nurses' confidence in their discussion skills may increase advance
      directive discussions.

PMID- 15466615
TI  - Designing a data and safety monitoring plan.
AB  - Evidence-based nursing practice is now the expected standard of care intensifying
      the need to conduct clinical research studies to investigate the efficacy of
      nursing interventions. To ensure that the urgency to document such efficacy does
      not compromise human participant safety, government research funding agencies are
      advocating special procedures to protect individuals who voluntarily participate
      in research studies. The National Institutes of Health application for clinical
      trial funding requires a data and safety monitoring plan (DSMP) to enhance human
      participant safety and clinical research integrity. This article describes an
      approach to developing a DSMP that includes a study risk assessment and a
      monitoring design based on that assessment.

PMID- 15466616
TI  - The Johnson-Neyman procedure as an alternative to ANCOVA.
AB  - ANCOVA is a widely used statistical procedure that is particularly useful in
      analyzing data from experimental designs. There are, however, a number of
      assumptions that must be tested before proceeding with the ANCOVA. Of particular
      concern is the assumption of homogeneity of regression slopes (HOS). When the HOS
      assumption has been violated, the researcher needs to look for an alternative
      approach to the ANCOVA. The Johnson-Neyman procedure (J-N) is presented as such
      an alternative. Although the calculations for the procedure are somewhat tedious
      and are not currently a standard feature of statistical software packages, an
      alternative approach using SAS syntax codes is presented.

PMID- 15466617
TI  - A Turkish language equivalence of the Exercise of Self-Care Agency Scale.
AB  - This article is about the pilot test of a Turkish version of the Exercise of Self
      Care Agency Scale (ESCA) using a randomized convenience sample of 119 bilingual
      Turkish adolescents. The instrument was translated into Turkish, back translated,
      and pilot tested to linguistic equivalence. Bilingual participants were randomly
      assigned to four groups. Each participant was administered both the English and
      the Turkish versions of the scale but in different order at 5-week intervals. The
      results show that the Turkish version of the ESCA was linguistically equal to the
      English form. Test-retest correlations were acceptably high (r = .80 to .90).
      Internal consistency of the total scale of the ESCA was adequate, with an alpha
      coefficient of .89 for the Turkish version and .88 for the English version.
      Further research in the development of this translated form would need to
      demonstrate its applicability and generalizability to monolingual Turkish
      adolescents.

PMID- 15466618
TI  - C1q governs deposition of circulating immune complexes and leukocyte Fcgamma
      receptors mediate subsequent neutrophil recruitment.
AB  - Inflammation induced by circulating immunoglobulin G-immune complexes (ICs)
      characterizes many immune-mediated diseases. In this work, the molecular
      requirements for the deposition of circulating ICs and subsequent acute leukocyte
      recruitment in mice were elucidated. We show that after intravenous injection,
      preformed soluble ICs are rapidly deposited in the postcapillary venules of the
      cremaster microcirculation, secondary to increased vascular permeability. This
      deposition is dependent on complement C1q. IC deposition is associated with
      leukocyte recruitment. Leukocyte rolling, which is mediated by P-selectin in the
      exteriorized cremaster muscle, is not further increased in response to ICs. In
      contrast, leukocyte rolling velocity is significantly decreased and leukocyte
      adhesion is significantly increased in the presence of ICs. The IC-mediated slow
      leukocyte rolling velocity and subsequent adhesion and emigration are dependent
      on Fcgamma receptors (FcgammaRs), particularly FcgammaRIII, with complement C3
      and C5 having no detectable role. These studies suggest a regulatory mechanism of
      IC deposition and leukocyte trafficking in IC-mediated inflammation requiring C1q
      and FcgammaRs in sequential, noninteracting roles.

PMID- 15466619
TI  - Imaging the single cell dynamics of CD4+ T cell activation by dendritic cells in
      lymph nodes.
AB  - The adaptive immune response is initiated in secondary lymphoid organs by contact
      between antigen-bearing dendritic cells (DCs) and antigen-specific CD4+ T cells.
      However, there is scant information regarding the single cell dynamics of this
      process in vivo. Using two-photon microscopy, we imaged the real-time behavior of
      naive CD4+ T cells and in vivo-labeled DCs in lymph nodes during a robust T cell
      response. In the first 2 h after entry into lymph nodes, T cells made short-lived
      contacts with antigen-bearing DCs, each contact lasting an average of 11-12 min
      and occurring mainly on dendrites. Altered patterns of T cell motility during
      this early stage of antigen recognition promoted serial engagement with several
      adjacent DCs. Subsequently, T cell behavior progressed through additional
      distinct stages, including long-lived clusters, dynamic swarms, and finally
      autonomous migration punctuated by cell division. These observations suggest that
      the immunological synapse in native tissues is remarkably fluid, and that stable
      synapses form only at specific stages of antigen presentation to T cells.
      Furthermore, the serial nature of these interactions implies that T cells
      activate by way of multiple antigen recognition events.

PMID- 15466620
TI  - Basophils initiate IL-4 production during a memory T-dependent response.
AB  - Experiments were performed to characterize and identify the cellular sources of
      the secondary interleukin (IL)-4 response to a T cell-dependent antigen. Mice
      were primed by immunization with goat anti-mouse immunoglobulin (Ig)D antibody
      (GaMD), which stimulates naive CD4+ T cells to secrete IL-4 in 3-4 d. When
      challenged with goat serum 14 d after immunization, GaMD-primed mice generated an
      IL-4 response that exceeded the primary response by approximately 100-fold,
      started in <2 h, and lasted for 4 d. Studies with 4get mice, in which cells with
      an accessible Il4 gene express a green fluorescent protein (GFP), revealed CD4+
      memory T cells, natural killer T cells, basophils, mast cells, and eosinophils as
      possible rapid producers of IL-4. GFP(+)CD4+ T cells and basophils expanded more
      in the spleen than the other cell types during the primary response to GaMD.
      Quantitation of in vivo IL-4 production by the in vivo cytokine capture assay
      after individual cell types were selectively stimulated or deleted demonstrated
      that basophils and memory CD4+ T cells account for most of the secondary IL-4
      response, with basophils initiating that response through IgE/FcepsilonRI
      mediated signaling but secreting IL-4 for <4 h and memory T cells secreting IL-4
      within 4 h and continuing to secrete this cytokine for 4 d.

PMID- 15466621
TI  - GATA-2 plays two functionally distinct roles during the ontogeny of hematopoietic
      stem cells.
AB  - GATA-2 is an essential transcription factor in the hematopoietic system that is
      expressed in hematopoietic stem cells (HSCs) and progenitors. Complete deficiency
      of GATA-2 in the mouse leads to severe anemia and embryonic lethality. The role
      of GATA-2 and dosage effects of this transcription factor in HSC development
      within the embryo and adult are largely unexplored. Here we examined the effects
      of GATA-2 gene dosage on the generation and expansion of HSCs in several
      hematopoietic sites throughout mouse development. We show that a haploid dose of
      GATA-2 severely reduces production and expansion of HSCs specifically in the
      aorta-gonad-mesonephros region (which autonomously generates the first HSCs),
      whereas quantitative reduction of HSCs is minimal or unchanged in yolk sac, fetal
      liver, and adult bone marrow. However, HSCs in all these ontogenically distinct
      anatomical sites are qualitatively defective in serial or competitive
      transplantation assays. Also, cytotoxic drug-induced regeneration studies show a
      clear GATA-2 dose-related proliferation defect in adult bone marrow. Thus, GATA-2
      plays at least two functionally distinct roles during ontogeny of HSCs: the
      production and expansion of HSCs in the aorta-gonad-mesonephros and the
      proliferation of HSCs in the adult bone marrow.

PMID- 15466622
TI  - A subset of liver NK T cells is activated during Leishmania donovani infection by
      CD1d-bound lipophosphoglycan.
AB  - Natural killer (NK) T cells are activated by synthetic or self-glycolipids and
      implicated in innate host resistance to a range of viral, bacterial, and
      protozoan pathogens. Despite the immunogenicity of microbial lipoglycans and
      their promiscuous binding to CD1d, no pathogen-derived glycolipid antigen
      presented by this pathway has been identified to date. In the current work, we
      show increased susceptibility of NK T cell-deficient CD1d(-/-) mice to Leishmania
      donovani infection and Leishmania-induced CD1d-dependent activation of NK T cells
      in wild-type animals. The elicited response was Th1 polarized, occurred as early
      as 2 h after infection, and was independent from IL-12. The Leishmania surface
      glycoconjugate lipophosphoglycan, as well as related glycoinositol phospholipids,
      bound with high affinity to CD1d and induced a CD1d-dependent IFNgamma response
      in naive intrahepatic lymphocytes. Together, these data identify Leishmania
      surface glycoconjugates as potential glycolipid antigens and suggest an important
      role for the CD1d-NK T cell immune axis in the early response to visceral
      Leishmania infection.

PMID- 15466623
TI  - Bruton's tyrosine kinase is essential for human B cell tolerance.
AB  - Most polyreactive and antinuclear antibodies are removed from the human antibody
      repertoire during B cell development. To elucidate how B cell receptor (BCR)
      signaling may regulate human B cell tolerance, we tested the specificity of
      recombinant antibodies from single peripheral B cells isolated from patients
      suffering from X-linked agammaglobulinemia (XLA). These patients carry mutations
      in the Bruton's tyrosine kinase (BTK) gene that encode an essential BCR signaling
      component. We find that in the absence of Btk, peripheral B cells show a distinct
      antibody repertoire consistent with extensive secondary V(D)J recombination.
      Nevertheless, XLA B cells are enriched in autoreactive clones. Our results
      demonstrate that Btk is essential in regulating thresholds for human B cell
      tolerance.

PMID- 15466624
TI  - CXCR2- and E-selectin-induced neutrophil arrest during inflammation in vivo.
AB  - The signaling events leading to the activation of integrins and firm arrest of
      rolling neutrophils in inflamed venules have yet to be elucidated. In vitro
      assays suggest that both E-selectin and chemokines can trigger arrest of rolling
      neutrophils, but E-selectin(-/-) mice have normal levels of adherent neutrophils
      in inflamed venules. To test whether chemokine-induced neutrophil arrest in vivo
      can be unmasked by blocking E-selectin, we investigated neutrophil adhesion in
      inflamed cremaster muscle venules in tumor necrosis factor (TNF)-alpha-treated
      CXCR2(-/-) or wild-type (WT) mice injected with E-selectin blocking monoclonal
      antibody (mAb) 9A9. To block chemokine receptor signaling, we investigated E
      selectin(-/-) or WT mice treated with pertussis toxin (PTx) intravenously.
      Neutrophil adhesion was unchanged in CXCR2(-/-), E-selectin(-/-), PTx-treated WT,
      or mAb 9A9-treated WT mice. However, TNF-alpha-induced neutrophil adhesion was
      almost completely abrogated in E-selectin(-/-) mice treated with PTx and
      significantly reduced in CXCR2(-/-) mice treated with the E-selectin blocking
      mAb. In thioglycollate-induced peritonitis, PTx treatment blocked neutrophil
      recruitment into the peritoneum of E-selectin(-/-) mice, but had only a partial
      effect in WT animals. These data show that E-selectin- and chemokine-mediated
      arrest mechanisms are overlapping in this model and identify CXCR2 as an
      important neutrophil arrest chemokine in vivo.

PMID- 15466625
TI  - Impaired cerebral autoregulation in patients with malignant hypertension.
AB  - BACKGROUND: In patients with a malignant hypertension, immediate parenteral
      treatment with blood pressure-lowering agents such as intravenous sodium
      nitroprusside (SNP) is indicated. In this study, we evaluated static and dynamic
      cerebral autoregulation (CA) during acute blood pressure lowering with SNP in
      these patients. METHODS AND RESULTS: In 8 patients with mean arterial pressure
      (MAP) >140 mm Hg and grade III or IV hypertensive retinopathy at hospital
      admission, middle cerebral artery blood velocity (MCA V) and blood pressure were
      monitored. Dynamic CA was expressed as the 0.1-Hz MCA V(mean) to MAP phase lead
      and static CA as the MCA V(mean) to MAP relationship during SNP treatment. Eight
      normotensive subjects served as a reference group. In the patients, the MCA
      V(mean) to MAP phase lead was lower (30+/-8 degrees versus 58+/-5 degrees ,
      mean+/-SEM; P<0.05), whereas the transfer gain tended to be higher. During SNP
      treatment, target MAP was reached within 90 minutes in all patients. The MCA
      V(mean) decrease was 22+/-4%, along with a 27+/-3% reduction in MAP (from 166+/-4
      to 121+/-6 mm Hg; P<0.05) in a linear fashion (averaged slope, 0.82+/-0.15% cm x
      s(-1) . % mm Hg(-1); r=0.70+/-0.07). CONCLUSIONS: In patients with malignant
      hypertension, dynamic CA is impaired. An MCA V(mean) plateau was not detected
      during the whole SNP treatment, indicating loss of static CA as well. This study
      showed that during the whole rapid reduction in blood pressure with SNP, MCA
      V(mean) decreases almost one on one with MAP.

PMID- 15466626
TI  - Coronary artery calcification and family history of premature coronary heart
      disease: sibling history is more strongly associated than parental history.
AB  - BACKGROUND: The objective of the study was to assess the association of a family
      history (FH) of premature coronary heart disease (CHD) with coronary artery
      calcification (CAC) in asymptomatic individuals and to compare the effects of
      sibling or parental FH on the risk of subclinical atherosclerosis. METHODS AND
      RESULTS: CAC by electron beam tomography was performed in 8549 asymptomatic
      individuals (69% men; mean age, 52+/-9 years). The prevalence and odds of any CAC
      and extent of CAC stratified according to FH of premature CHD were determined.
      Those with (1) no FH of CHD, (2) FH of premature CHD in parents, or (3) FH in
      siblings had a prevalence of CAC of 55%, 64%, and 78% (P<0.0001) among men and
      27%, 36%, and 56% (P<0.0001) among women, respectively. The multivariate
      regression analysis demonstrated that the odds ratio (95% confidence interval)
      for the presence of CAC was 1.3 (1.1 to 1.6) among those with positive FH of
      premature CHD in parents only, 2.3 (1.7 to 3.1) and 2.5 (1.8 to 3.3) among those
      in siblings and a combined FH compared with those without FH of CHD in men,
      respectively. Among women, the corresponding odds ratios were 1.3 (1.0 to 1.8),
      2.3 (1.7 to 3.6), and 1.9 (1.3 to 3.1), respectively. A similar trend was
      observed in the association of FH of premature CHD with increasing CAC scores.
      CONCLUSIONS: Our study demonstrates a highly significant association between FH
      of premature CHD and the presence and extent of CAC. Furthermore, within the
      limits of self-reporting of family history, our findings suggest that a sibling
      history is more strongly associated with subclinical coronary atherosclerosis
      than a parental history of premature CHD.

PMID- 15466627
TI  - Endothelium-restricted overexpression of human endothelin-1 causes vascular
      remodeling and endothelial dysfunction.
AB  - BACKGROUND: Endothelin (ET)-1 is a potent vasoconstrictor that contributes to
      vascular remodeling in hypertension and other cardiovascular diseases. Endogenous
      ET-1 is produced predominantly by vascular endothelial cells. To directly test
      the role of endothelium-derived ET-1 in cardiovascular pathophysiology, we
      specifically targeted expression of the human preproET-1 gene to the endothelium
      by using the Tie-2 promoter in C57BL/6 mice. METHODS AND RESULTS: Ten-week-old
      male C57BL/6 transgenic (TG) and nontransgenic (wild type; WT) littermates were
      studied. TG mice exhibited 3-fold higher vascular tissue ET-1 mRNA and 7-fold
      higher ET-1 plasma levels than did WT mice but no significant elevation in blood
      pressure. Despite the absence of significant blood pressure elevation, TG mice
      exhibited marked hypertrophic remodeling and oxidant excess-dependent endothelial
      dysfunction of resistance vessels, altered ET-1 and ET-3 vascular responses, and
      significant increases in ET(B) expression compared with WT littermates. Moreover,
      TG mice generated significantly higher oxidative stress, possibly through
      increased activity and expression of vascular NAD(P)H oxidase than did their WT
      counterparts. CONCLUSIONS: In this new murine model of endothelium-restricted
      human preproET-1 overexpression, ET-1 caused structural remodeling and
      endothelial dysfunction of resistance vessels, consistent with a direct
      nonhemodynamic effect of ET-1 on the vasculature, at least in part through the
      activation of vascular NAD(P)H oxidase.

PMID- 15466628
TI  - Human study of biatrial electrical coupling: determinants of endocardial septal
      activation and conduction over interatrial connections.
AB  - BACKGROUND: The relative contribution of the atrial septum and interatrial
      connections to biatrial activation is a fundamental concept of human cardiac
      electrophysiology that has yet to be fully characterized. The purpose of the
      present study was to determine how both atria are coupled electrically. METHODS
      AND RESULTS: Twenty patients (16 men; mean age 54+/-11years) with a history of
      symptomatic atrial fibrillation (AF) underwent simultaneous biatrial noncontact
      mapping before catheter ablation of AF. The multiple electrode array catheters
      were positioned, respectively, in the left atrium (LA; transseptally) and the
      right atrium (RA). In all but 2 patients, isopotential maps revealed that
      endocardial septal activations of the RA and LA were separate, independent, and
      asynchronous of each other. Interatrial conduction was related to the site of
      initial atrial depolarization, revealing conduction over Bachmann's bundle in all
      patients during sinus rhythm, high RA pacing, and pacing from the LA appendage.
      Pacing from the coronary sinus was associated with conduction over the
      interatrial connection at the level of the coronary sinus in all patients, and
      conduction over Bachmann's bundle also occurred in 5 (26%) of 19 patients.
      Interatrial conduction over the fossa ovalis occurred in only 2 (2%) of the 116
      segments analyzed. CONCLUSIONS: Electrical coupling of the RA and LA in humans is
      predominantly provided by muscular connections at the level of Bachmann's bundle
      and the coronary sinus. The true septum (the fossa ovalis and its limbus) of the
      RA and LA is asynchronous and discordant, usually without contralateral
      conduction during sinus rhythm or atrial pacing.

PMID- 15466629
TI  - Hypertrophy, fibrosis, and sudden cardiac death in response to pathological
      stimuli in mice with mutations in cardiac troponin T.
AB  - BACKGROUND: Transgenic mouse models expressing a missense mutation (R92Q) or a
      splice donor site mutation (trunc) in the cardiac troponin T (cTnT) model
      familial hypertrophic cardiomyopathy (FHC) in humans. Although males from these
      strains share the unusual property of having significantly smaller ventricles and
      cardiac myocytes, they differ with regard to systolic function, fibrosis, and
      gene expression. Little is known about how these phenotypes affect the responses
      to additional pathological stimuli. METHODS AND RESULTS: We tested the ability of
      hearts of both sexes of wild-type and mutant mice to respond to defined
      pathological, pharmacological, hypertrophic stimuli in vivo. Hearts of mutant
      cTnT models of both sexes were able to undergo hypertrophy in response to at
      least one stimulus, but the extent differed between the 2 mutants and was sex
      specific. Interestingly, the trunc-mutant mouse heart was resistant to the
      development of fibrosis in response to pharmacological stimuli. Stimulation with
      2 adrenergic agonists led to sudden cardiac death of all male but not female
      mutant animals, which suggests altered adrenergic responsiveness in these 2
      models of FHC. CONCLUSIONS: Hypertrophic signaling is differentially affected by
      distinct mutations in cTnT and is sex modified. Hearts can respond with either an
      augmented hypertrophic and fibrotic response or a diminished hypertrophy and
      resistance to fibrosis. Sudden cardiac death is related to adrenergic stress and
      is independent of the development of fibrosis but occurred only in male mice.
      These results suggest that patients with certain TnT mutations may respond to
      certain pathological situations with a worsened phenotype.

PMID- 15466631
TI  - Balloon dilation of severe aortic stenosis in the fetus: potential for prevention
      of hypoplastic left heart syndrome: candidate selection, technique, and results
      of successful intervention.
AB  - BACKGROUND: Preventing the progression of fetal aortic stenosis (AS) to
      hypoplastic left heart syndrome (HLHS) requires identification of fetuses with
      salvageable left hearts who would progress to HLHS if left untreated, a
      successful in utero valvotomy, and demonstration that a successful valvotomy
      promotes left heart growth in utero. Fetuses meeting the first criterion are
      undefined, and previous reports of fetal AS dilation have not evaluated the
      impact of intervention on in utero growth of left heart structures. METHODS AND
      RESULTS: We offered fetal AS dilation to 24 mothers whose fetuses had AS. At
      least 3 echocardiographers assigned a high probability that all 24 fetuses would
      progress to HLHS if left untreated. Twenty (21 to 29 weeks' gestation) underwent
      attempted AS dilation, with technical success in 14. Ideal fetal positioning for
      cannula puncture site and course of the needle (with or without laparotomy)
      proved to be necessary for procedural success. Serial fetal echocardiograms after
      intervention demonstrated growth arrest of the left heart structures in
      unsuccessful cases and in those who declined the procedure, while ongoing left
      heart growth was seen in successful cases. Resumed left heart growth led to a 2
      ventricle circulation at birth in 3 babies. CONCLUSIONS: Fetal echocardiography
      can identify midgestation fetuses with AS who are at high risk for developing
      HLHS. Timely and successful aortic valve dilation requires ideal fetal and
      cannula positioning, prevents left heart growth arrest, and may result in normal
      ventricular anatomy and function at birth.

PMID- 15466630
TI  - Chondrogenic and adipogenic potential of microvascular pericytes.
AB  - BACKGROUND: Previous studies have shown that pericytes can differentiate into
      osteoblasts and form bone. This study investigated whether pericytes can also
      differentiate into chondrocytes and adipocytes. METHODS AND RESULTS: Reverse
      transcription-polymerase chain reaction demonstrated that pericytes express mRNA
      for the chondrocyte markers Sox9, aggrecan, and type II collagen. Furthermore,
      when cultured at high density in the presence of a defined chondrogenic medium,
      pericytes formed well-defined pellets comprising cells embedded in an
      extracellular matrix rich in sulfated proteoglycans and type II collagen. In
      contrast, when endothelial cells were cultured under the same conditions, the
      pellets disintegrated after 48 hours. In the presence of adipogenic medium,
      pericytes but not endothelial cells expressed mRNA for peroxisome proliferator
      activated receptor-gamma2 (an adipocyte-specific transcription factor) and
      incorporated lipid droplets that stained with oil red O. To confirm that
      pericytes can differentiate along the chondrocytic and adipocytic lineages in
      vivo, these cells were inoculated into diffusion chambers and implanted into
      athymic mice for 56 days. Accordingly, mineralized cartilage, fibrocartilage, and
      a nonmineralized cartilaginous matrix with lacunae containing chondrocytes were
      observed within these chambers. Small clusters of cells that morphologically
      resembled adipocytes were also identified. CONCLUSIONS: These data demonstrate
      that pericytes are multipotent cells that may contribute to growth, wound
      healing, repair, and/or the development and progression of various pathological
      states.

PMID- 15466632
TI  - Differential effects of theophylline on sympathetic excitation, hemodynamics, and
      breathing in congestive heart failure.
AB  - BACKGROUND: Patients with heart failure have high levels of central sympathetic
      outflow and also have a high prevalence of sleep-related breathing disorders,
      predominantly central sleep apnea. The options for treating central sleep apnea
      in heart failure are limited and include theophylline. Whether theophylline
      alters sympathetic activity in heart failure patients is not known. METHODS AND
      RESULTS: Using a single-blinded, randomized, placebo-controlled study design, we
      investigated the sympathetic, hemodynamic, neurohumoral, and ventilatory effects
      of theophylline in patients with congestive heart failure compared with healthy
      control subjects closely matched for age, sex, and body mass index. Theophylline
      increased muscle sympathetic nerve activity and lowered transcutaneous CO2 in the
      control subjects but only lowered transcutaneous CO2 in the heart failure
      patients. Theophylline nearly doubled plasma renin concentration in both the
      healthy subjects (P<0.01) and the heart failure patients (P<0.02). CONCLUSIONS:
      Our study shows that in heart failure patients, there are differential effects of
      theophylline: in contrast to healthy subjects, theophylline does not increase
      sympathetic activity in heart failure, whereas increases in plasma renin and
      ventilation are still evident. These novel findings may have important
      implications for understanding the potential harmful and beneficial effects of
      theophylline and related substances in heart failure patients.

PMID- 15466633
TI  - Histological correlates of carotid plaque surface morphology on lumen contrast
      imaging.
AB  - BACKGROUND: Carotid angiographic plaque surface morphology is a powerful risk
      factor for stroke and systemic vascular risk. However, the underlying pathology
      is unclear, and a better understanding is required both to evaluate other forms
      of carotid imaging and to develop new treatments. Previous studies comparing
      angiographic plaque surface morphology with pathology have been small and
      unblinded, and the vast majority assessed only the crude macroscopic appearance
      of the plaque. We performed the first large study comparing angiographic surface
      morphology with detailed histology. METHODS AND RESULTS: Carotid plaque surface
      morphology was classified as ulcerated, irregular, or smooth on 128 conventional
      selective carotid artery angiograms from consecutive patients undergoing
      endarterectomy for severe symptomatic stenosis. Blinded angiographic assessments
      were compared with 10 histological features recorded on detailed microscopy of
      the plaque using reproducible semiquantitative scales. Angiographic ulceration
      was associated with plaque rupture (P=0.001), intraplaque hemorrhage (P=0.001),
      large lipid core (P=0.005), less fibrous tissue (P=0.003), and increased
      instability overall (P=0.001). For example, angiographically ulcerated plaques
      were much more likely than smooth plaques to be ruptured (OR=15.4, 95% CI=2.7 to
      87.3, P<0.001), show a large lipid core (OR=26.7, 95% CI=2.6 to 270, P<0.001) or
      a large hemorrhage (OR=17.0, 95% CI=2.0 to 147, P=0.02). The equivalent odds
      ratios for angiographically irregular versus smooth plaque were 6.3 (1.3 to 31,
      P=0.02), 6.7 (1.5 to 30, P=0.008), and 9.2 (1.1 to 77, P=0.02), respectively.
      CONCLUSIONS: In contrast to previous studies based on macroscopic assessment, we
      found very strong associations between detailed histology and carotid
      angiographic plaque surface morphology. Plaque surface morphology on carotid
      angiography is a highly sensitive marker of plaque instability. Studies of the
      predictive value of MR- and CT-based lumen contrast plaque surface imaging are
      required.

PMID- 15466634
TI  - KATP channel activation induces ischemic preconditioning of the endothelium in
      humans in vivo.
AB  - BACKGROUND: Endothelial dysfunction contributes to ischemia-reperfusion injury
      (IRI) and is reduced by ischemic preconditioning (IPC). IPC may involve
      activation of ATP-sensitive potassium channels (K(ATP)). We determined whether
      modulation of K(ATP) channels occurs in endothelial IPC in humans. METHODS AND
      RESULTS: IRI of the forearm was induced by inflating a blood pressure cuff to 200
      mm Hg for 20 minutes in healthy volunteers. K(ATP) activation was modulated by
      intra-arterial glibenclamide (blocker) and diazoxide (opener). Endothelial
      function (response to intra-arterial acetylcholine) was assessed with forearm
      plethysmography before and after (1) 15-minute reperfusion, (2) IRI preceded by
      IPC (3 five-minute periods of ischemia), (3) IRI preceded by IPC with
      glibenclamide, (4) IPC followed by glibenclamide before IRI, (5) IRI preceded by
      diazoxide, and (6) IRI preceded by coinfusion of glibenclamide with diazoxide.
      IRI caused endothelial dysfunction (P=0.002), which IPC prevented (P=0.40).
      Glibenclamide abolished IPC when given contemporaneously with (P=0.003) or during
      IRI (P=0.0005). Diazoxide prevented endothelial dysfunction after IRI (P=0.68)
      but not when coinfused with glibenclamide. CONCLUSIONS: Glibenclamide abolishes
      and diazoxide mimics endothelial IPC in humans. The time course of the effect of
      glibenclamide suggests involvement of K(ATP) channels as effectors of endothelial
      IPC in vivo. These data may have implications for understanding the therapeutic
      role of agents that modulate K(ATP) channel function.

PMID- 15466635
TI  - Heparin and air filters reduce embolic events caused by intra-arterial cerebral
      angiography: a prospective, randomized trial.
AB  - BACKGROUND: Intra-arterial cerebral angiography is associated with a low risk for
      neurological complications, but clinically silent ischemic events after
      angiography have been seen in a substantial number of patients. METHODS AND
      RESULTS: In a prospective study, diffusion-weighted magnetic resonance imaging
      (DW-MRI) before and after intra-arterial cerebral angiography and transcranial
      Doppler sonography during angiography were used to evaluate the frequency of
      cerebral embolism. One hundred fifty diagnostic cerebral angiographies were
      randomized into 50 procedures, each using conventional angiographic technique, or
      systemic heparin treatment throughout the procedure, or air filters between the
      catheter and both the contrast medium syringe and the catheter flushing. There
      was no neurological complication during or after angiography. Overall, DW-MRI
      revealed 26 new ischemic lesions in 17 patients (11%). In the control group, 11
      patients showed a total of 18 lesions. In the heparin group, 3 patients showed a
      total of 4 lesions. In the air filter group, 3 patients exhibited a total of 4
      lesions. The reduced incidence of ischemic events in the heparin and air filter
      groups compared with the control group was significantly different (P=0.002).
      Transcranial Doppler sonography demonstrated a large number of microembolic
      signals that was significantly lower in the air filter group compared with the
      heparin and control groups (P<0.01), which did not differ from each other.
      CONCLUSIONS: Air filters and heparin both reduce the incidence of silent ischemic
      events detected by DW-MRI after intra-arterial cerebral angiography and can
      potentially lower clinically overt ischemic complications. This may apply to any
      intra-arterial angiographic procedure.

PMID- 15466636
TI  - Signaling molecules in overcirculation-induced pulmonary hypertension in piglets:
      effects of sildenafil therapy.
AB  - BACKGROUND: The phosphodiesterase type-5 (PDE-5) inhibitor sildenafil has been
      reported to improve pulmonary arterial hypertension (PAH), but the mechanisms
      that account for this effect are incompletely understood. Severe pulmonary
      hypertension has been characterized by defects in a signaling pathway involving
      angiopoietin-1 and the bone morphogenetic receptor-2 (BMPR-2). We investigated
      the effects of sildenafil on hemodynamics and signaling molecules in a piglet
      overcirculation-induced model of early PAH. METHODS AND RESULTS: Thirty 3-week
      old piglets were randomized to placebo or sildenafil therapy 0.75 mg/kg TID after
      anastomosis of the left subclavian artery to the pulmonary arterial trunk or
      after a sham operation. Three months later, the animals underwent a hemodynamic
      evaluation followed by pulmonary tissue sampling for morphometry,
      immunohistochemistry or radioimmunoassay, and real-time quantitative-polymerase
      chain reaction. Chronic systemic-to-pulmonary shunting increased pulmonary mRNA
      for angiopoietin-1, endothelin-1 (ET-1), angiotensin II, inducible nitric oxide
      synthase, vascular endothelial growth factor, and PDE-5. Pulmonary messenger RNA
      for BMPR-1A and BMPR-2 decreased. Pulmonary angiotensin II, ET-1, and vascular
      endothelial growth factor proteins increased. Pulmonary artery pressure increased
      from 20+/-2 to 33+/-1 mm Hg, and arteriolar medial thickness increased by 91%.
      The expressions of angiopoietin-1, ET-1, and angiotensin II were tightly
      correlated to pulmonary hypertension. Sildenafil prevented the increase in
      pulmonary artery pressure, limited the increase in medial thickness to 41%, and
      corrected associated biological perturbations except for the angiopoietin-1/BMPR
      2 pathway, PDE-5, and angiotensin II. CONCLUSIONS: Sildenafil partially prevents
      overcirculation-induced PAH and associated changes in signaling molecules.
      Angiotensin II, PDE-5, and angiopoietin-1/BMPR-2 signaling may play a dominant
      role in the early stages of the disease.

PMID- 15466637
TI  - Mother rotors and the mechanisms of D600-induced type 2 ventricular fibrillation.
AB  - BACKGROUND: Two types of ventricular fibrillation (VF) have been demonstrated in
      isolated rabbit hearts during D600 infusion. Type 1 VF is characterized by the
      presence of multiple, wandering wavelets, whereas type 2 VF shows local
      spatiotemporal periodicity. We hypothesized that a single mother rotor underlies
      type 2 VF. METHODS AND RESULTS: One (protocol I) or 2 (protocol II) cameras were
      used to map the epicardial ventricular activations in Langendorff-perfused rabbit
      hearts. Multiple episodes of type 2 VF were induced in 22 hearts by high
      concentration (> or =2.5 mg/L) D600 (protocol I). During type 2 VF, a single
      spiral wave (n=19) and/or an epicardial breakthrough pattern (n=11) was present
      in 14 hearts. These spiral waves either slowly drifted or intermittently anchored
      on the papillary muscle (PM) of the left ventricle. Dominant-frequency (DF)
      analyses showed that the highest local DF was near the PM (12.5+/-1.1 Hz). There
      was an excellent correlation between the highest local DF of these spiral waves
      and breakthroughs (11.8+/-1.7 Hz) and the DF of simultaneously obtained global
      pseudo-ECG (11.2+/-1.8 Hz, r=0.97, P<0.0001) during type 2 VF. We also
      successfully reproduced the major features of type 2 VF by using the Luo-Rudy
      action-potential model in a simulated, 3-dimensional tissue slab, under
      conditions of reduced excitability and flat action-potential duration
      restitution. CONCLUSIONS: Either a stationary or a slowly drifting mother rotor
      can result in type 2 VF. Colocalization of the stationary mother rotors with the
      PM suggests the importance of underlying anatomic structures in mother rotor
      formation.

PMID- 15466639
TI  - Ambient pollution and blood pressure in cardiac rehabilitation patients.
AB  - BACKGROUND: Multiple studies have demonstrated a consistent association between
      ambient particulate air pollution and increased risk of hospital admissions and
      deaths for cardiovascular causes. We investigated the associations between fine
      particulate pollution (PM2.5) and blood pressure during 631 repeated visits for
      cardiac rehabilitation in 62 Boston residents with cardiovascular disease.
      METHODS AND RESULTS: Blood pressure, cardiac risk factor, and exercise data were
      abstracted from records of rehabilitation visits between 1999 and 2001. We
      applied mixed-effect models, controlling for body mass index, age, gender, number
      of visits, hour of day, and weather variables. For an increase from the 10th to
      the 90th percentile in mean PM2.5 level during the 5 days before the visit (10.5
      microg/m3), there was a 2.8-mm Hg (95% CI, 0.1 to 5.5) increase in resting
      systolic, a 2.7-mm Hg (95% CI, 1.2 to 4.3) increase in resting diastolic, and a
      2.7-mm Hg (95% CI, 1.0 to 4.5) increase in resting mean arterial blood pressure.
      The mean PM2.5 level during the 2 preceding days (13.9 microg/m3) was associated
      with a 7.0-mm Hg (95% CI, 2.3 to 12.1) increase in diastolic and a 4.7-mm Hg (95%
      CI, 0.5 to 9.1) increase in mean arterial blood pressure during exercise in
      persons with resting heart rate > or =70 bpm, but it was not associated with an
      increase in blood pressure during exercise in persons with heart rate <70 bpm.
      CONCLUSIONS: In patients with preexisting cardiac disease, particle pollution may
      contribute to increased risk of cardiac morbidity and mortality through short
      term increases in systemic arterial vascular narrowing, as manifested by
      increased peripheral blood pressure.

PMID- 15466638
TI  - Risk of coronary artery disease associated with polymorphism of the cytochrome
      P450 epoxygenase CYP2J2.
AB  - BACKGROUND: Cytochrome P450 (CYP) 2J2 is expressed in the vascular endothelium
      and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids
      (EETs). The EETs are potent endogenous vasodilators and inhibitors of vascular
      inflammation. However, it is not known whether genetic polymorphisms of CYP2J2
      are associated with increased cardiovascular risks. METHODS AND RESULTS: All 9
      exons of the CYP2J2 gene and its proximal promoter were sequenced in 132 patients
      to identify potential variants. Functional consequence of a single nucleotide
      polymorphism (SNP) in the promoter of CYP2J2 was further evaluated by use of
      transcription factor-binding and reporter assays. A total of 17 polymorphisms
      were identified. One of the most relevant polymorphisms in terms of frequency and
      functional importance is located at -50 (G-50T) in the proximal promoter of
      CYP2J2. Screening of 289 patients with coronary artery disease and 255 control
      subjects revealed 77 individuals with the G-50T SNP (17.3% of coronary artery
      disease patients, 10.6% of control subjects; P=0.026). The association of the G
      50T polymorphism remained significant after adjustment for age, gender, and
      conventional cardiovascular risk factors (OR, 2.23; 95% CI, 1.04 to 4.79). The G
      50T mutation resulted in the loss of binding of the Sp1 transcription factor to
      the CYP2J2 promoter and resulted in a 48.1+/-2.4% decrease in CYP2J2 promoter
      activity (P<0.01). Plasma concentrations of stable EET metabolites were
      significantly lower in individuals with the G-50T SNP. CONCLUSIONS: A
      functionally relevant polymorphism of the CYP2J2 gene is independently associated
      with an increased risk of coronary artery disease.

PMID- 15466640
TI  - Complete isolation of left atrium surrounding the pulmonary veins: new insights
      from the double-Lasso technique in paroxysmal atrial fibrillation.
AB  - BACKGROUND: Paroxysmal atrial fibrillation (PAF) can be eliminated with
      continuous circular lesions (CCLs) around the pulmonary veins (PVs), but it is
      unclear whether all PVs are completely isolated. METHODS AND RESULTS: Forty-one
      patients with symptomatic PAF underwent 3D mapping, and all PV ostia were marked
      on the 3D map based on venography. Irrigated radiofrequency energy was applied at
      a distance from the PV ostia guided by 2 Lasso catheters placed within the
      ipsilateral superior and inferior PVs. The mean radiofrequency duration was
      1550+/-511 seconds for left-sided PVs and 1512+/-506 seconds for right-sided PVs.
      After isolation, automatic activity was observed in the right-sided PVs in 87.8%
      and in the left-sided PVs in 80.5%. During the procedure, a spontaneous or
      induced PV tachycardia (PVT) with a cycle length of 189+/-29 ms was observed in
      19 patients. During a mean follow-up of 6 months, atrial tachyarrhythmias
      recurred in 10 patients. Nine patients underwent a repeat procedure. Conduction
      gaps in the left CCL in 9 patients and in the right CCL in 2 patients were closed
      during the second procedure. A spontaneous PVT with a cycle length of 212+/-44 ms
      was demonstrated in 7 of 9 patients, even though no PVT had been observed in 6 of
      these 7 patients during the first procedure. No AF recurred in 39 patients after
      PV isolation during follow-up. CONCLUSIONS: Automatic activity and fast
      tachycardia within the PVs could reflect an arrhythmogenic substrate in patients
      with PAF, which could be eliminated by isolating all PVs with CCLs guided by 3D
      mapping and the double-Lasso technique in the majority of patients.

PMID- 15466641
TI  - Role of myocardial neuronal nitric oxide synthase-derived nitric oxide in beta
      adrenergic hyporesponsiveness after myocardial infarction-induced heart failure
      in rat.
AB  - BACKGROUND: An emerging concept is that a neuronal isoform of nitric oxide
      synthase (NOS1) may regulate myocardial contractility. However, a role for NOS1
      derived nitric oxide (NO) in heart failure (HF) has not been defined. METHODS AND
      RESULTS: Using a model of myocardial infarction-induced HF, we demonstrated that
      cardiac NOS1 expression and activity increased in HF rats (P<0.05 and P<0.001
      versus shams, respectively). This was associated with translocation of NOS1 from
      the ryanodine receptor to the sarcolemma through interactions with caveolin-3 in
      HF hearts. With ex vivo and in vivo pressure-volume analysis, cardiac NOS1
      derived NO was found to be negatively inotropic in shams but not HF hearts.
      Ventricular elastance (E(es)) was significantly reduced in HF rats (P<0.05), and
      tau, the time constant of left ventricular relaxation, was prolonged (both
      P<0.05). Acute NOS1 inhibition significantly increased E(es) by 33+/-3% and tau
      by 17+/-2% (P<0.05) in shams, although these effects were significantly
      attenuated in HF hearts. beta-Adrenergic stimulation induced a marked increase in
      systolic performance in sham hearts, with the responses being significantly
      blunted in HF hearts. E(es) increased by 163+/-42% (P<0.01) in sham hearts and
      56+/-9% in HF hearts, and LV +dP/dt increased by 97+/-9% (P<0.01) in shams and
      37+/-7% (P<0.05) in the HF group. Interestingly, preferential NOS1 inhibition
      enhanced the blunted responses of LV +dP/dt and E(es) to beta-adrenergic
      stimulation in HF rats but had no effect in shams. CONCLUSIONS: These results
      provide the first evidence that increased NOS1-derived NO production may play a
      role in the autocrine regulation of myocardial contractility in HF.

PMID- 15466642
TI  - Spectrum and frequency of cardiac channel defects in swimming-triggered
      arrhythmia syndromes.
AB  - BACKGROUND: Swimming is a relatively genotype-specific arrhythmogenic trigger for
      type 1 long-QT syndrome (LQT1). We hypothesize that mimickers of concealed LQT1,
      namely catecholaminergic polymorphic ventricular tachycardia (CPVT), may also
      underlie swimming-triggered cardiac events. METHODS AND RESULTS: Between August
      1997 and May 2003, 388 consecutive, unrelated patients were referred specifically
      for LQTS genetic testing. The presence of a personal and/or family history of a
      near-drowning or drowning was determined by review of the medical records and/or
      phone interviews and was blinded to genetic test results. Comprehensive
      mutational analysis of the 5 LQTS-causing channel genes, KCNQ1 (LQT1), KCNH2
      (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6), along with KCNJ2 (Andersen
      Tawil syndrome) and targeted analysis of 18 CPVT1-associated exons in RyR2, was
      performed with the use of denaturing high-performance liquid chromatography and
      direct DNA sequencing. Approximately 11% (43 of 388) of the index cases had a
      positive swimming phenotype. Thirty-three of these 43 index cases had a
      "Schwartz" score (> or =4) suggesting high clinical probability of LQTS. Among
      this subset, 28 patients (85%) were LQT1, 2 patients (6%) were LQT2, and 3 were
      genotype negative. Among the 10 cases with low clinical probability for LQTS, 9
      had novel, putative CPVT1-causing RyR2 mutations. CONCLUSIONS: In contrast to
      previous studies that suggested universal LQT1 specificity, genetic heterogeneity
      underlies channelopathies that are suspected chiefly because of a near-drowning
      or drowning. CPVT1 and strategic genotyping of RyR2 should be considered when
      LQT1 is excluded in the pathogenesis of a swimming-triggered arrhythmia syndrome.

PMID- 15466643
TI  - SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and
      arrhythmia.
AB  - BACKGROUND: We studied a large family affected by an autosomal dominant cardiac
      conduction disorder associated with sinus node dysfunction, arrhythmia, and right
      and occasionally left ventricular dilatation and dysfunction. Previous linkage
      analysis mapped the disease phenotype to a 30-cM region on chromosome 3p22-p25
      (CMD1E). This region also contains a locus for right ventricular cardiomyopathy
      (ARVD5) and the cardiac sodium channel gene (SCN5A), mutations that cause
      isolated progressive cardiac conduction defect (Lenegre syndrome), long-QT
      syndrome (LQT3), and Brugada syndrome. METHODS AND RESULTS: Family members were
      studied, and the positional candidate gene SCN5A was screened for mutations. We
      identified, by direct sequencing, a heterozygous G-to-A mutation at position 3823
      that changed an aspartic acid to asparagine (D1275N) in a highly conserved
      residue of exon 21. This mutation was present in all affected family members, was
      absent in 300 control chromosomes, and predicted a change of charge within the S3
      segment of domain III. CONCLUSIONS: Our findings expand the clinical spectrum of
      disorders of the cardiac sodium channel to include cardiac dilation and
      dysfunction and support the hypothesis that genes encoding ion channels can be
      implicated in dilated cardiomyopathies.

PMID- 15466644
TI  - Effect of candesartan on cause-specific mortality in heart failure patients: the
      Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity
      (CHARM) program.
AB  - BACKGROUND: Patients with heart failure are at increased risk of sudden death and
      death attributed to progressive pump failure. We assessed the effect of
      candesartan on cause-specific mortality in patients enrolled in the Candesartan
      in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM)
      program. METHODS AND RESULTS: The CHARM program consisted of 3 component trials
      that enrolled patients with symptomatic heart failure: CHARM-Alternative (n=2028;
      LVEF<=40% [corrected] and ACE intolerant), CHARM-Added (n=2548; LVEF<=40%,
      [corrected] already on ACE inhibitors), and CHARM-Preserved (n=3023; LVEF >40%).
      Patients were randomized to candesartan, titrated to 32 mg QD, or placebo and
      were followed up for a median of 37.7 months. All deaths were reviewed by a
      blinded adjudication committee and categorized according to prespecified
      definitions on the basis of a narrative and source documentation. The number and
      rate of deaths by cause were calculated for each of the component trials and the
      overall program. Of all the patients, 8.5% died suddenly, and 6.2% died of
      progressive heart failure. Candesartan reduced both sudden death (HR 0.85 [0.73
      to 0.99], P=0.036) and death from worsening heart failure (HR 0.78 [0.65 to
      0.94], P=0.008). These reductions were most apparent in the patients with
      LVEF<=40% [corrected]. CONCLUSIONS: Candesartan reduced sudden death and death
      from worsening heart failure in patients with symptomatic heart failure, although
      this reduction was most apparent in patients with systolic dysfunction.

PMID- 15466645
TI  - Giant fetal magnetocardiogram P waves in congenital atrioventricular block: a
      marker of cardiovascular compensation?
AB  - BACKGROUND: Cardiogram signal amplitude is a key index of hypertrophy but has not
      been investigated extensively in utero. In this study, magnetocardiography was
      used to assess P and QRS amplitude in normal subjects and subjects with fetal
      arrhythmia. METHODS AND RESULTS: The study cohort consisted of 68 normal fetuses
      and 25 with various arrhythmias: 9 reentrant supraventricular tachycardia (SVT),
      2 ventricular tachycardia (VT), 2 sinus tachycardia, 2 blocked atrial bigeminy, 2
      congenital second-degree atrioventricular (AV) block, and 8 congenital complete
      AV block. Subjects with congenital AV block, all presenting with bradycardia,
      showed large QRS amplitude, exceedingly large P-wave amplitude, and long P-wave
      duration. The 2 subjects with VT, both with poor ventricular function, also
      exhibited large P waves. SVT was associated with only moderate signal amplitude
      elevation. CONCLUSIONS: The data imply that AV block in utero is accompanied by
      hypertrophy, which is more pronounced for the atria than the ventricles. We
      hypothesize that the hypertrophy results from a compensatory response associated
      with regulation of cardiac output and is likely to be observable in other
      arrhythmias and disease states. Magnetocardiography may be more sensitive than
      fetal echocardiography for detection of atrial hypertrophy in utero.

PMID- 15466646
TI  - Epicardial stenosis severity does not affect minimal microcirculatory resistance.
AB  - BACKGROUND: Whether minimal microvascular resistance of the myocardium is
      affected by the presence of an epicardial stenosis is controversial. Recently, an
      index of microcirculatory resistance (IMR) was developed that is based on
      combined measurements of distal coronary pressure and thermodilution-derived mean
      transit time. In normal coronary arteries, IMR correlates well with true
      microvascular resistance. However, to be applicable in the case of an epicardial
      stenosis, IMR should account for collateral flow. We investigated the feasibility
      of determining IMR in humans and tested the hypothesis that microvascular
      resistance is independent of epicardial stenosis. METHODS AND RESULTS: Thirty
      patients scheduled for percutaneous coronary intervention were studied. The
      stenosis was stented with a pressure guidewire, and coronary wedge pressure
      (P(w)) was measured during balloon occlusion. After successful stenting, a short
      compliant balloon with a diameter 1.0 mm smaller than the stent was placed in the
      stented segment and inflated with increasing pressures, creating a 10%, 50%, and
      75% area stenosis. At each of the 3 degrees of stenosis, fractional flow reserve
      (FFR) and IMR were measured at steady-state maximum hyperemia induced by
      intravenous adenosine. A total of 90 measurements were performed in 30 patients.
      When uncorrected for P(w), an apparent increase in microvascular resistance was
      observed with increasing stenosis severity (IMR=24, 27, and 37 U for the 3
      different degrees of stenosis; P<0.001). In contrast, when P(w) is appropriately
      accounted for, microvascular resistance did not change with stenosis severity
      (IMR=22, 23, and 23 U, respectively; P=0.28). CONCLUSIONS: Minimal microvascular
      resistance does not change with epicardial stenosis severity, and IMR is a
      specific index of microvascular resistance when collateral flow is properly taken
      into account.

PMID- 15466647
TI  - In situ Akt phosphorylation in the nucleus tractus solitarii is involved in
      central control of blood pressure and heart rate.
AB  - BACKGROUND: Previously, we have shown that nitric oxide (NO) plays a significant
      role in central cardiovascular regulation and modulates the baroreflex in the
      nucleus tractus solitarii (NTS) of rats. NO production is mediated by activation
      of NO synthase (NOS). Insulin signaling was involved in controlling peripheral
      blood pressure via the activation of endothelial NOS. Here, we investigated
      whether the insulin signal transduction pathway is involved in controlling
      central cardiovascular effects. METHODS AND RESULTS: Insulin was injected into
      NTS of urethane-anesthetized male Wistar-Kyoto (WKY) rats. Unilateral
      microinjection (60 nL) of insulin (100 IU/mL) into the NTS produced prominent
      depressor and bradycardic effects in 8- and 16-week-old WKY rats. In addition,
      pretreatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and
      the NOS inhibitor L-NAME into the NTS caused attenuation of the cardiovascular
      response evoked by insulin in either 8- or 16-week-old WKY rats. Western blot
      analysis showed a significant increase (2.6+/-0.4-fold; P<0.05) in Akt
      phosphorylation after insulin injection, whereas LY294002 abolished the insulin
      induced effects. In situ Akt phosphorylation was found in NTS by
      immunohistochemistry analysis after injection of insulin. This in situ Akt
      phosphorylation was abolished significantly after injection of LY294002.
      CONCLUSIONS: Take together, these results suggest that the insulin-PI3K-Akt-NOS
      signaling pathway may play a significant role in central cardiovascular
      regulation.

PMID- 15466648
TI  - Atherosclerosis in patients infected with HIV is influenced by a mutant monocyte
      chemoattractant protein-1 allele.
AB  - BACKGROUND: Patients infected with HIV present with premature atherosclerosis,
      and the 2 diseases share common pathogenic pathways. We investigated mutations in
      the monocyte chemoattractant protein-1 (MCP-1) and CCR-2 genes, which are known
      to control aspects of these pathways, to ascertain whether they are involved in
      atherogenesis in these patients. METHODS AND RESULTS: We performed carotid and
      femoral artery ultrasonography to detect subclinical atherosclerosis in patients
      infected with HIV (n=183). MCP-1-2518G and CCR-2 64I polymorphisms were
      determined in the HIV group and in a population-based control group (n=348). We
      also determined MCP-1 circulating levels in the HIV group. The presence of MCP-1
      2518G in the group of patients with subclinical atherosclerosis was significantly
      higher than in patients without atherosclerotic lesions (47.5% versus 18.2%,
      respectively; P<0.001). Furthermore, the patients with atherosclerotic lesions
      had higher MCP-1 plasma concentrations than did patients without lesions (74.15
      [4.03] versus 57.81 [3.67] pg/mL, respectively; P=0.03). When adjusted for known
      cardiovascular risk factors, the MCP-1-2518G allele was associated with
      subclinical atherosclerosis (OR 5.72, 95% CI 1.74 to 18.80, P=0.004). Compared
      with measurements conducted approximately 2.5 years earlier in a subset of 40
      patients, intima-media thickness (IMT) in the carotid artery progressed at a mean
      rate of 0.06 mm/y more rapidly in patients bearing the MCP-1-mutated allele
      (P=0.08). CONCLUSIONS: HIV-infected patients with the MCP-1-2518G allele have a 5
      fold increased risk for atherosclerosis, as assessed by ultrasonography.

PMID- 15466649
TI  - Allopurinol attenuates left ventricular remodeling and dysfunction after
      experimental myocardial infarction: a new action for an old drug?
AB  - BACKGROUND: Accumulating evidence suggests a critical role for increased reactive
      oxygen species (ROS) production in left ventricular (LV) remodeling and
      dysfunction after myocardial infarction (MI). Increased expression of xanthine
      oxidase (XO), a major source of ROS, has recently been demonstrated in
      experimental and clinical heart failure; however, a potential role for LV
      remodeling processes remains unclear. We therefore studied the effect of long
      term treatment with allopurinol, a potent XO inhibitor, on myocardial ROS
      production and LV remodeling and dysfunction after MI. METHODS AND RESULTS: Mice
      with extensive anterior MI (n=105) were randomized to treatment with either
      vehicle or allopurinol (20 mg x kg(-1) x d(-1) by gavage) for 4 weeks starting on
      day 1 after surgery. Infarct size was similar among the groups. XO expression and
      activity were markedly increased in the remote myocardium of mice after MI, as
      determined by electron spin resonance spectroscopy. Myocardial ROS production was
      increased after MI but markedly reduced after allopurinol treatment. Importantly,
      allopurinol treatment substantially attenuated LV cavity dilatation and
      dysfunction after MI, as assessed by echocardiography, and markedly reduced
      myocardial hypertrophy and interstitial fibrosis. CONCLUSIONS: The present study
      reveals a novel beneficial effect of treatment with allopurinol, ie, a marked
      attenuation of LV remodeling processes and dysfunction after experimental MI.
      Allopurinol treatment therefore represents a potential novel strategy to prevent
      LV remodeling and dysfunction after MI.

PMID- 15466650
TI  - Soluble guanylate cyclase activator reverses acute pulmonary hypertension and
      augments the pulmonary vasodilator response to inhaled nitric oxide in awake
      lambs.
AB  - BACKGROUND: Inhaled nitric oxide (NO) is a potent and selective pulmonary
      vasodilator, which induces cGMP synthesis by activating soluble guanylate cyclase
      (sGC) in ventilated lung regions. Carbon monoxide (CO) has also been proposed to
      influence smooth muscle tone via activation of sGC. We examined whether direct
      stimulation of sGC by BAY 41-2272 would produce pulmonary vasodilation and
      augment the pulmonary responses to inhaled NO or CO. METHODS AND RESULTS: In
      awake, instrumented lambs, the thromboxane analogue U-46619 was intravenously
      administered to increase mean pulmonary arterial pressure to 35 mm Hg.
      Intravenous infusion of BAY 41-2272 (0.03, 0.1, and 0.3 mg x kg(-1) x h(-1))
      reduced mean pulmonary arterial pressure and pulmonary vascular resistance and
      increased transpulmonary cGMP release in a dose-dependent manner. Larger doses of
      BAY 41-2272 also produced systemic vasodilation and elevated the cardiac index.
      N(omega)-nitro-l-arginine methyl ester abolished the systemic but not the
      pulmonary vasodilator effects of BAY 41-2272. Furthermore, infusing BAY 41-2272
      at 0.1 mg x kg(-1) x h(-1) potentiated and prolonged the pulmonary vasodilation
      induced by inhaled NO (2, 10, and 20 ppm). In contrast, inhaled CO (50, 250, and
      500 ppm) had no effect on U-46619-induced pulmonary vasoconstriction before or
      during administration of BAY 41-2272. CONCLUSIONS: In lambs with acute pulmonary
      hypertension, BAY 41-2272 is a potent pulmonary vasodilator that augments and
      prolongs the pulmonary vasodilator response to inhaled NO. Direct pharmacological
      stimulation of sGC, either alone or in combination with inhaled NO, may provide a
      novel approach for the treatment of pulmonary hypertension.

PMID- 15466651
TI  - Left ventricular form and function: scientific priorities and strategic planning
      for development of new views of disease.

PMID- 15466652
TI  - Images in cardiovascular medicine. Calcified pleural plaque can rupture thoracic
      aorta.

PMID- 15466653
TI  - Images in cardiovascular medicine. Evaluation of coronary artery aneurysms in
      Kawasaki disease by multislice computed tomographic coronary angiography.

PMID- 15466654
TI  - ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report
      of the American College of Cardiology/American Heart Association Task Force on
      Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery
      Bypass Graft Surgery).

PMID- 15466655
TI  - Percutaneous heart valve replacement: enthusiasm tempered.

PMID- 15466656
TI  - Statin-induced improvement of endothelial progenitor cell mobilization,
      myocardial neovascularization, left ventricular function, and survival after
      experimental myocardial infarction requires endothelial nitric oxide synthase.
AB  - BACKGROUND: Endothelial nitric oxide (eNO) bioavailability is severely reduced
      after myocardial infarction (MI) and in heart failure. Statins enhance eNO
      availability by both increasing eNO production and reducing NO inactivation. We
      therefore studied the effect of statin treatment on eNO availability after MI and
      tested its role for endothelial progenitor cell mobilization, myocardial
      neovascularization, left ventricular (LV) dysfunction, remodeling, and survival
      after MI. METHODS AND RESULTS: Wild-type (WT) and eNO synthase (eNOS)-/- mice
      with extensive anterior MI were randomized to treatment with vehicle (V) or
      atorvastatin (Ator, 50 mg/kg QD by gavage) for 4 weeks starting on day 1 after
      MI. Ator markedly improved endothelium-dependent, NO-mediated vasorelaxation;
      mobilization of endothelial progenitor cells; and myocardial neovascularization
      of the infarct border in WT mice after MI while having no effect in eNOS-/- mice.
      LV dysfunction and interstitial fibrosis were markedly attenuated by Ator in WT
      mice, whereas no effect was observed in eNOS-/- mice after MI. Importantly, Ator
      significantly increased the survival rate during 4 weeks after MI in WT mice
      (Ator versus V, 80% versus 46%; P<0.01, n=75) but not in eNOS-/- mice (43% versus
      48%; NS, n=42). CONCLUSIONS: These findings suggest that increased eNO
      availability is required for statin-induced improvement of endothelial progenitor
      cell mobilization, myocardial neovascularization, LV dysfunction, interstitial
      fibrosis, and survival after MI. eNO bioavailability after MI likely represents
      an important therapeutic target in heart failure after MI and mediates beneficial
      effects of statin treatment after MI.

PMID- 15466657
TI  - Genetic basis of atherosclerosis: part II: clinical implications.

PMID- 15466658
TI  - Cognitive impairment and blood pressure: quo usque tandem abutere patientia
      nostra?

PMID- 15466659
TI  - Plasma cGMP and large artery remodeling in asymptomatic men.
AB  - cGMP regulates vascular smooth muscle tone and arterial wall response to
      proliferative signals. We determined plasma cGMP and carotid artery intima-media
      thickness (IMT) and diameter in 84 asymptomatic men submitted to investigation of
      their cardiovascular risk profiles. Plasma cGMP was positively associated with
      IMT (P<0.01) and diameter (P<0.05), independently of coexisting risk factors.
      These associations were reinforced in the subgroup of subjects with high
      sensitivity C-reactive protein level or multiple atherosclerotic plaques. A
      positive relationship existed between diameter and IMT (P<0.01) and disappeared
      after cGMP adjustment. This suggests a link between cGMP pathway and arterial
      wall geometry that is revealed by vascular injury conditions and may participate
      in early large artery remodeling.

PMID- 15466660
TI  - Cyclophilin A functions as an endogenous inhibitor for membrane-bound guanylate
      cyclase-A.
AB  - Cyclophilin A (CypA), a receptor for the immunosuppressive agent cyclosporin A,
      is a cis-trans-peptidyl-prolyl isomerase (PPIase). It accelerates the cis-trans
      isomerization of prolyl-peptide bonds. CypA binds and regulates the activity of a
      variety of proteins. Atrial natriuretic factor (ANF) and its receptor membrane
      bound guanylate cyclase-A (GC-A) are involved in the regulation of blood
      pressure. We examined whether CypA affects the activation of GC-A by ANF. The
      results showed that CypA associated with GC-A. Interestingly, binding of ANF to
      GC-A released CypA. Transfection of CypA inhibited ANF-stimulated GC-A activity,
      indicating that CypA functions as an endogenous inhibitor for GC-A activation.
      CypA also inhibits the activity of guanylate cyclase-C (GC-c), the catalytic
      domain of GC-A, indicating that CypA interacts with the catalytic domain of GC-A.
      In contrast, transfection of CypA R55A, a CypA mutant expressing low PPIase
      activity, did not significantly attenuate the activity of GC-c and the activation
      of GC-A. Inhibition of PPIase activity of CypA with cyclosporin A also blocks the
      inhibitory effect of CypA on GC-c activity. These results demonstrate that PPIase
      activity is required for CypA to inhibit GC-c activity and GC-A activation by
      ANF. Furthermore, mutation of Pro 822, 902, or 958 in GC-c abolished its
      activity. Therefore, it is likely that CypA binds to GC-A and catalyzes the cis
      trans isomerization of Pro 822, 902, or 958, which keeps GC-A in the inactive
      state, and that binding of ANF to GC-A alters the conformation of the catalytic
      domain that releases CypA from GC-A leading to enzyme activation.

PMID- 15466661
TI  - Blood pressure-related cognitive decline: does age make a difference?
AB  - Systolic and diastolic blood pressures have been inversely related to cognitive
      performance in prospective and cross-sectional studies. However, in large,
      community-based samples, these findings have been limited to older adults. In
      this 20-year longitudinal study, we examined the relationship between baseline
      blood pressure and cognitive decline for 529 participants using 2 age groups (18
      to 46 years and 47 to 83 years). Cognitive performance was measured over multiple
      examinations with the Wechsler Adult Intelligence Scale from which 4 scores were
      derived by factor analysis. A 2-stage growth curve method of analysis was used to
      model cognitive change. Results indicated that higher levels of baseline systolic
      blood pressure, diastolic blood pressure, mean arterial pressure, and blood
      pressure categories as defined by the Joint National Committee on Prevention,
      Detection, Evaluation, and Treatment of High Blood Pressure were significantly
      associated with decline in Visualization/Fluid abilities in both younger and
      older age groups. Young adults are as susceptible to blood pressure-related
      longitudinal decline in cognitive performance as are older adults.

PMID- 15466662
TI  - The association between blood pressure, hypertension, and cerebral white matter
      lesions: cardiovascular determinants of dementia study.
AB  - Cerebral white matter lesions are frequently observed on magnetic resonance
      imaging (MRI) scans in elderly people and are associated with stroke and
      dementia. Elevated blood pressure is presumed one of the main risk factors,
      although data are almost exclusively derived from cross-sectional studies. We
      assessed in 10 European cohorts the relation between concurrently and previously
      measured blood pressure levels, hypertension, its treatment, and severe cerebral
      white matter lesions. In total, 1805 nondemented subjects aged 65 to 75 years
      were sampled from ongoing community-based studies that were initiated 5 to 20
      years before the MRI. White matter lesions in the periventricular and subcortical
      region were rated separately using semiquantitative measures. We performed
      logistic regression analyses adjusted for potential confounders in 1625 people
      with complete data. Concurrently and formerly assessed diastolic and systolic
      blood pressure levels were positively associated with severe white matter
      lesions. Both increases and decreases in diastolic blood pressure were associated
      with more severe periventricular white matter lesions. Increase in systolic blood
      pressure levels was associated with more severe periventricular and subcortical
      white matter lesions. People with poorly controlled hypertension had a higher
      risk of severe white matter lesions than those without hypertension, or those
      with controlled or untreated hypertension. Higher blood pressure was associated
      with an increased risk of severe white matter lesions. Successful treatment of
      hypertension may reduce this risk; however, a potential negative effect of
      decreasing diastolic blood pressure level on the occurrence of severe
      periventricular white matter lesions should be taken into account.

PMID- 15466663
TI  - Gender-specific influence of NO synthase gene on blood pressure since childhood:
      the Bogalusa Heart Study.
AB  - Impaired endothelial function caused by decreased NO production plays a
      pathophysiologic role in essential hypertension. Although cross-sectional data
      are available on the association between endothelial NO synthase gene
      polymorphisms and hypertension, whether the gene variants and their haplotypes
      affect the long-term cumulative burden and trend of blood pressure since
      childhood is not known. This aspect was examined using 4 polymorphisms and a
      community-based longitudinal cohort of 347 blacks and 801 whites aged 18 to 45
      years who have been examined serially 4 to 13 times (7705 observations) over an
      on average of 23.4 years. The area under the curve calculated using a growth
      curve of serial measurements of mean arterial pressure was used as a long-term
      cumulative burden. Blacks compared with whites displayed significantly lower
      frequencies of the rare alleles for G894T (0.112 versus 0.325), G10T (0.209
      versus 0.323), T-786C (0.147 versus 0.372), and A-922G (0.131 versus 0.355). In
      addition, T-786C and A-922G polymorphisms were in complete linkage disequilibrium
      in both races. After adjusting for age and body mass index, the 894T and 10T
      alleles were significantly associated with lower long-term burden of blood
      pressure since childhood in black females and white females, respectively. With
      respect to haplotypes, the G894-10T carriers compared with (G894-G10)/(G894-G10)
      showed significantly lower long-term burden and trend of blood pressure in white
      females. In conclusion, the endothelial NO synthase gene influences the long-term
      burden and trend of blood pressure since childhood in females and may contribute
      to their predisposition to hypertension.

PMID- 15466664
TI  - Critical role for the alpha-1B adrenergic receptor at the sympathetic
      neuroeffector junction.
AB  - The alpha-1 adrenergic receptors (alpha(1)ARs) are critical in sympathetically
      mediated vasoconstriction. The specific role of each alpha(1)AR subtype in
      regulating vasoconstriction remains highly controversial. Limited pharmacological
      studies suggest that differential alpha(1)AR responses may be the result of
      differential activation of junctional versus extrajunctional receptors. We tested
      the hypothesis that the alpha(1B)AR subtype is critical in mediating sympathetic
      junctional neurotransmission. We measured in vivo integrated cardiovascular
      responses to a hypotensive stimulus (induced via transient bilateral carotid
      occlusion [TBCO]) in alpha(1B)AR knockout (KO) mice and their wild-type (WT)
      littermates. In WT mice, after dissection of the carotid arteries and denervation
      of aortic baroreceptor buffering nerves, TBCO produced significant pressor and
      positive inotropic effects. Both responses were markedly attenuated in
      alpha(1B)AR KO mice (change systolic blood pressure 46+/-8 versus 11+/-2 mm Hg;
      percentage change in the end-systolic pressure-volume relationship [ESPVR] 36+/
      7% versus 12+/-2%; WT versus KO; P<0.003). In vitro alpha(1)AR mesenteric
      microvascular contractile responses to endogenous norepinephrine (NE; elicited by
      electrical field stimulation 10 Hz) was markedly depressed in alpha(1B)AR KO mice
      compared with WT (12.4+/-1.7% versus 21.5+/-1.2%; P<0.001). In contrast,
      responses to exogenous NE were similar in alpha(1B)AR KO and WT mice (22.4+/-7.3%
      versus 33.4+/-4.3%; NS). Collectively, these results demonstrate a critical role
      for the alpha(1B)AR in baroreceptor-mediated adrenergic signaling at the vascular
      neuroeffector junction. Moreover, alpha(1B)ARs modulate inotropic responses to
      baroreceptor activation. The critical role for alpha(1B)AR in neuroeffector
      regulation of vascular tone and myocardial contractility has profound clinical
      implications for designing therapies for orthostatic intolerance.

PMID- 15466665
TI  - More on the sodium saga.

PMID- 15466666
TI  - Mechanisms for aldosterone and spironolactone-induced positive inotropic actions
      in the rat heart.
AB  - Previously, we reported that aldosterone and spironolactone have inotropic
      effects in the isolated perfused heart. To address the mechanisms underlying
      these inotropic effects, we examined the effects of aldosterone and
      spironolactone on isolated cardiac myocyte shortening, intracellular calcium
      ([Ca+2]i), pHi, and calcium-dependent actinomyosin ATPase activity. Aldosterone
      significantly increased shortening in cardiac myocytes (8.0+/-1.0 versus 16.0+/
      1.3%, P<0.01) but neither diastolic [Ca+2]i (61.0+/-1.1 versus 66.0+/-4.4 nmol/L)
      nor peak systolic [Ca+2]i (302+/-11 versus 304+/-17 nmol/L) was affected.
      Spironolactone-increased shortening was also not coupled with changes in peak
      systolic calcium; however, diastolic calcium was significantly increased by
      spironolactone. Aldosterone, but not spironolactone, increased pHi from 7.23+/
      0.03 to 7.59+/-0.02 (P<0.01); this was completely blocked by coadministration of
      100 micromol/L of ethyl-isopropyl amiloride (EIPA), an inhibitor of the Na+/H+
      exchanger (P<0.01). Consistent with this finding, aldosterone increased cytosolic
      sodium concentration ([Na+]i) from 9.2+/-0.15 to 11.4+/-0.2 mmol/L and produced a
      leftward shift in the pCa ATPase curve (pCa=5.82+/-0.02 versus 6.35+/-0.02,
      P<0.01) without affecting maximal myosin ATPase activity. Conversely,
      spironolactone, but not aldosterone, significantly increases maximal actomyosin
      ATPase activity (837+/-59 versus 355+/-52 nmol inorganic phosphate (P(i)) x min(
      1) x g tissue(-1)). Collectively, these data strongly suggest that the inotropic
      actions of aldosterone and spironolactone are caused by different mechanisms of
      action. Aldosterone appeared to increase inotropy primarily through increased
      cytosolic pH, whereas spironolactone increased myosin ATPase calcium sensitivity
      and diastolic calcium concentration.

PMID- 15466667
TI  - Angiotensin II regulation of collagen type I expression in cardiac fibroblasts:
      modulation by PPAR-gamma ligand pioglitazone.
AB  - Angiotensin II (Ang II)-mediated stimulation of fibroblast growth and collagen
      type I synthesis is believed to be an important component of the cardiac
      remodeling process in hypertension and chronic ischemia. Ang II-mediated
      oxidative stress could be important in enhanced fibroblast growth and collagen
      formation. Accordingly, we postulated that the PPAR-gamma ligand, pioglitazone,
      which is known to modulate oxidative stress, would alter Ang II-induced formation
      of collagen type I in cardiac fibroblasts. Cardiac fibroblasts were treated with
      different concentrations (10(-8) to 10(-6) M) of Ang II for different times (6
      hours, 12 hours, and 24 hours). Ang II increased the expression of collagen type
      I in a concentration- and time-dependent fashion (P<0.01 versus control). Ang II
      also decreased the expression and activity of matrix metalloproteinase (MMP)-1
      (MMP-1, P<0.05 versus control). These effects of Ang II were attenuated by
      pretreatment of cells with pioglitazone (10 micromol/L). Ang II stimulated the
      intracellular generation of reactive oxygen species (ROS), and this effect was
      also attenuated by pioglitazone. Ang II treatment activated the redox-sensitive
      transcription factor NF-kappaB, and pioglitazone pretreatment blocked this effect
      of Ang II. Ang II also activated another transcription factor, AP-1, but this
      effect of Ang II was not modulated by pioglitazone. In other experiments, we
      observed that trolox, the water soluble analog of vitamin E, attenuated the
      effects of Ang II on the expression of collagen type I and MMP-1, in a manner
      similar to pioglitazone. Thus, pioglitazone attenuates Ang II-mediated collagen
      type I synthesis in cardiac fibroblasts. The effects of pioglitazone are mediated
      by the modulation of ROS release and redox-sensitive transcription factor NF
      kappaB.

PMID- 15466668
TI  - Mechanisms for increased glycolysis in the hypertrophied rat heart.
AB  - Glycolysis increases in hypertrophied hearts but the mechanisms are unknown. We
      studied the regulation of glycolysis in hearts with pressure-overload LV
      hypertrophy (LVH), a model that showed marked increases in the rates of
      glycolysis (by 2-fold) and insulin-independent glucose uptake (by 3-fold).
      Although the V(max) of the key glycolytic enzymes was unchanged in this model,
      concentrations of free ADP, free AMP, inorganic phosphate (P(i)), and fructose
      2,6-bisphosphate (F-2,6-P2), all activators of the rate-limiting enzyme
      phosphofructokinase (PFK), were increased (up to 10-fold). Concentrations of the
      inhibitors of PFK, ATP, citrate, and H+ were unaltered in LVH. Thus, our findings
      show that increased glucose entry and activation of the rate-limiting enzyme PFK
      both contribute to increased flux through the glycolytic pathway in hypertrophied
      hearts. Moreover, our results also suggest that these changes can be explained by
      increased intracellular free [ADP] and [AMP], due to decreased energy reserve in
      LVH, activating the AMP-activated protein kinase cascade. This, in turn, results
      in enhanced synthesis of F-2,6-P2 and increased sarcolemma localization of
      glucose transporters, leading to coordinated increases in glucose transport and
      activation of PFK.

PMID- 15466669
TI  - The maze.

PMID- 15466670
TI  - Association of genetic risks for schizophrenia and bipolar disorder with specific
      and generic brain structural endophenotypes.
AB  - CONTEXT: For more than a century, it has been uncertain whether or not the major
      diagnostic categories of psychosis--schizophrenia and bipolar disorder--are
      distinct disease entities with specific genetic causes and neuroanatomical
      substrates. OBJECTIVE: To investigate the relationship between genetic risk and
      structural variation throughout the entire brain in patients and their unaffected
      relatives sampled from multiply affected families with schizophrenia or bipolar
      disorder. DESIGN: Analysis of the association between genetic risk and variation
      in tissue volume on magnetic resonance images. SETTING: Psychiatric research
      center. PARTICIPANTS: Subjects comprised 25 patients with schizophrenia, 36 of
      their unaffected first-degree relatives, 37 patients with bipolar 1 disorder who
      experienced psychotic symptoms during illness exacerbation, and 50 of their
      unaffected first-degree relatives. MAIN OUTCOME MEASURES: We used computational
      morphometric techniques to map significant associations between a continuous
      measure of genetic liability for each subject and variation in gray or white
      matter volume. RESULTS: Genetic risk for schizophrenia was specifically
      associated with distributed gray matter volume deficits in the bilateral fronto
      striato-thalamic and left lateral temporal regions, whereas genetic risk for
      bipolar disorder was specifically associated with gray matter deficits only in
      the right anterior cingulate gyrus and ventral striatum. A generic association
      between genetic risk for both disorders and white matter volume reduction in the
      left frontal and temporoparietal regions was consistent with left frontotemporal
      disconnectivity as a genetically controlled brain structural abnormality common
      to both psychotic disorders. CONCLUSIONS: Genetic risks for schizophrenia and
      bipolar disorder are associated with specific gray matter but generic white
      matter endophenotypes. Thus, Emil Kraepelin's pivotal distinction was neither
      wholly right nor wholly wrong: the 2 major psychoses show both distinctive and
      similar patterns of brain structural abnormality related to variable genetic
      risk.

PMID- 15466672
TI  - Vulnerability before, during, and after a major depressive episode: a 3-wave
      population-based study.
AB  - BACKGROUND: Vulnerability as defined by high levels of neuroticism, low self
      esteem, and poor coping skills characterizes individuals with a history of major
      depressive episodes (MDEs). OBJECTIVE: To separate postmorbid vulnerability into
      (1) trait effects (ie, the continuation of premorbid vulnerability); (2) state
      effects of subthreshold (residual) symptoms on personality or its perception;
      and/or (3) scar effects (ie, negative personality change that develops during an
      MDE and persists beyond MDE remission). METHODS: Data come from the Netherlands
      Mental Health Survey and Incidence Study, a prospective Dutch psychiatric
      population-based survey. We obtained psychiatric (Composite International
      Diagnostic Interview) and personality data on neuroticism, depressive coping
      style, self-esteem, and mastery from 4796 respondents at 3 time points (T1, T2,
      and T3), 12 and 24 months apart. Between- and within-subjects differences were
      tested with repeated-measures analysis of variance and adjusted for sex, age, and
      time. RESULTS: After T1, 409 respondents developed an MDE, of whom 334 were MDE
      free at T3. In comparison with individuals without any lifetime MDE, the 262
      subjects with a first MDE had higher premorbid T1 vulnerability scores on each
      personality measure (0.38-0.83 effect size units). During the MDE, vulnerability
      scores further increased (0.33-0.52 effect size units) but returned to premorbid
      levels after MDE remission. We found no scar effects among subgroups with severe
      or long-lasting MDEs. Subthreshold residual symptoms at T3 biased comparisons
      between T1 and T3 if the premorbid period of T1 to MDE onset was longer than the
      postmorbid period of MDE remission to T3, misleadingly suggesting scar effects.
      We obtained similar results in the 147 subjects with recurrent MDEs. CONCLUSIONS:
      There was no evidence of a negative change from premorbid to postmorbid
      assessment for any of the personality traits. Postmorbid vulnerability reflected
      the continuation of premorbid vulnerability. Pre-post MDE comparisons are
      sensitive to prodromal and residual symptoms. Our findings suggest 2 independent
      simultaneous processes: (1) the ongoing expression of vulnerability as a
      personality deviance; and (2) synchrony of change between severity of depressive
      symptoms and personality deviance.

PMID- 15466671
TI  - Summer birth and deficit schizophrenia: a pooled analysis from 6 countries.
AB  - BACKGROUND: In some reports, summer birth has been associated with deficit
      schizophrenia. Deficit schizophrenia and nondeficit schizophrenia also differ in
      several other ways. OBJECTIVE: To conduct a combined analysis of the published
      and unpublished data sets from the northern hemisphere that relate deficit and
      nondeficit schizophrenia to month of birth. DATA SOURCES: Studies of season of
      birth in which it was possible to make a deficit/nondeficit categorization. STUDY
      SELECTION: Published studies with samples of convenience and all known population
      based studies with the deficit/nondeficit categorization were included. The
      studies came from 6 countries. DATA EXTRACTION: Three published studies of
      samples of convenience, 2 population-based prevalence studies, and 5 population
      based studies that approximated incident samples were included. Month of birth
      was compared for deficit and nondeficit schizophrenia, using meta-analytic fixed
      effects models. DATA SYNTHESIS: A group x month goodness-of-fit chi2 showed a
      significant difference between deficit and nondeficit subjects in season of birth
      (P < .001) in the studies that approximated incidence. This difference was
      largely due to an increase in deficit schizophrenia births in June and July (odds
      ratio, 1.9; 95% confidence interval, 1.3-2.9). Similar results were found in the
      prevalence studies. A similar pattern was found in 2 of the 3 samples of
      convenience, but when combined, these 3 samples did not show a significant
      deficit/nondeficit difference. CONCLUSIONS: Deficit schizophrenia has a season of
      birth pattern that differs from that of nondeficit schizophrenia. This analysis
      supports the notion of a separate disease within schizophrenia.

PMID- 15466673
TI  - The effects of pharmacologically induced hypogonadism on mood in healthy men.
AB  - BACKGROUND: The effects of declining androgen secretion on mood regulation and
      the potential psychotropic efficacy of androgen replacement in men are largely
      undetermined. OBJECTIVE: To examine the effects on mood of the acute suppression
      of testosterone secretion. DESIGN: A double-blind, placebo-controlled, crossover
      (self-as-own-control) study. SETTING: An ambulatory care clinic in a research
      hospital. PARTICIPANTS: Thirty-one healthy adult men with no history of
      psychiatric illness or substance or anabolic steroid abuse. INTERVENTIONS: Men
      received depot leuprolide acetate (Lupron, 7.5 mg intramuscularly) every 4 weeks
      for 3 months. After the first month of Lupron alone, all men received (in
      addition to Lupron) testosterone enanthate (200 mg intramuscular) or placebo
      (sesame oil as color-matched vehicle) every 2 weeks for 1 month each in a
      crossover design. The order of administration of testosterone and placebo was
      randomly assigned and counterbalanced. MAIN OUTCOME MEASURES: Mood and behavior
      rating scores (self-report and rater administered). RESULTS: With the exceptions
      of hot flushes, libido, and the feeling of being emotionally charged, none of the
      symptoms measured showed a significant difference across eugonadal, Lupron plus
      placebo, and Lupron plus testosterone conditions. Despite the absence of a
      uniform effect of Lupron plus placebo on mood, 3 men experienced clinically
      relevant mood symptoms during this induced hypogonadal condition. High baseline
      levels of sexual functioning predicted the greatest decline in sexual function
      during Lupron plus placebo. CONCLUSIONS: These data, the first to describe the
      effects on mood of induced hypogonadism in healthy young men, suggest that short
      term hypogonadism is sufficient to precipitate depressive symptoms in only a
      small minority of younger men. The predictors of this susceptibility remain to be
      determined.

PMID- 15466674
TI  - Fluoxetine, comprehensive cognitive behavioral therapy, and placebo in
      generalized social phobia.
AB  - BACKGROUND: Generalized social phobia is common, persistent, and disabling and is
      often treated with selective serotonin reuptake inhibitor drugs or cognitive
      behavioral therapy. OBJECTIVE: We compared fluoxetine (FLU), comprehensive
      cognitive behavioral group therapy (CCBT), placebo (PBO), and the combinations of
      CCBT/FLU and CCBT/PBO. DESIGN: Randomized, double-blind, placebo-controlled
      trial. SETTING: Two academic outpatient psychiatric centers. PATIENTS: Subjects
      meeting a primary diagnosis of generalized social phobia were recruited via
      advertisement. Seven hundred twenty-two were screened, and 295 were randomized
      and available for inclusion in an intention-to-treat efficacy analysis; 156
      (52.9%) were male, 226 (76.3%) were white, and mean age was 37.1 years.
      INTERVENTIONS: Treatment lasted for 14 weeks. Fluoxetine and PBO were
      administered at doses from 10 mg/d to 60 mg/d (or equivalent). Group
      comprehensive cognitive behavioral therapy was administered weekly for 14
      sessions. MAIN OUTCOME MEASURES: An independent blinded evaluator assessed
      response with the Brief Social Phobia Scale and Clinical Global Impressions
      scales as primary outcomes. A videotaped behavioral assessment served as a
      secondary outcome, using the Subjective Units of Distress Scale. Adverse effects
      were measured by self-rating. Each treatment was compared by means of chi2 tests
      and piecewise linear mixed-effects models. RESULTS: Clinical Global Impressions
      scales response rates in the intention-to-treat sample were 29 (50.9%) (FLU), 31
      (51.7%) (CCBT), 32 (54.2%) (CCBT/FLU), 30 (50.8%) (CCBT/PBO), and 19 (31.7%)
      (PBO), with all treatments being significantly better than PBO. On the Brief
      Social Phobia Scale, all active treatments were superior to PBO. In the linear
      mixed-effects models analysis, FLU was more effective than CCBT/FLU, CCBT/PBO,
      and PBO at week 4; CCBT was also more effective than CCBT/FLU and CCBT/PBO. By
      the final visit, all active treatments were superior to PBO but did not differ
      from each other. Site effects were found for the Subjective Units of Distress
      Scale assessment, with FLU and CCBT/FLU superior to PBO at Duke University
      Medical Center, Durham, NC. Treatments were well tolerated. CONCLUSIONS: All
      active treatments were superior to PBO on primary outcomes. Combined treatment
      did not yield any further advantage. Notwithstanding the benefits of treatment,
      many patients remained symptomatic after 14 weeks.

PMID- 15466675
TI  - Individual growth curve analysis illuminates stability and change in personality
      disorder features: the longitudinal study of personality disorders.
AB  - BACKGROUND: The long-term stability of personality pathology remains an open
      question. Its resolution will come from prospective, multiwave longitudinal
      studies using blinded assessments of personality disorders (PD). Informative
      analysis of multiwave data requires the application of statistical procedures,
      such as individual growth curve modeling, that can detect and describe individual
      change appropriately over time. The Longitudinal Study of Personality Disorders,
      which meets contemporary methodological design criteria, provides the data for
      this investigation of PD stability and change from an individual growth curve
      perspective. METHODS: Two hundred fifty subjects were examined for PD features at
      3 different time points using the International Personality Disorders Examination
      during a 4-year study. Stability and change in PD features over time were
      examined using individual growth modeling. RESULTS: Fitting of unconditional
      growth models indicated that statistically significant variation in PD features
      existed across time in the elevation and rate of change of the individual PD
      growth trajectories. Fitting of additional conditional growth models, in which
      the individual elevation and rate-of-change growth parameters were predicted by
      subjects' study group membership (no PD vs possible PD), sex, and age at entry
      into the study, showed that study group membership predicted the elevation and
      rate of change of the individual growth curves. Comorbid Axis I psychopathology
      and treatment during the study period were related to elevations of the
      individual growth trajectories, but not to rates of change. CONCLUSIONS: From the
      perspective of individual growth curve analysis, PD features show considerable
      variability across individuals over time. This fine-grained analysis of
      individual growth trajectories provides compelling evidence of change in PD
      features over time and does not support the assumption that PD features are
      traitlike, enduring, and stable over time.

PMID- 15466676
TI  - Major depressive disorder, suicidal ideation, and suicide attempt in twins
      discordant for cannabis dependence and early-onset cannabis use.
AB  - BACKGROUND: Previous research has reported both a moderate degree of comorbidity
      between cannabis dependence and major depressive disorder (MDD) and that early
      onset cannabis use is associated with increased risks for MDD. OBJECTIVE: To
      examine whether associations between both lifetime cannabis dependence and early
      cannabis use and measures of MDD, suicidal ideation, and suicide attempt persist
      after controlling for genetic and/or shared environmental influences. DESIGN:
      Cross-sectional survey of twin pairs discordant for lifetime cannabis dependence
      and those discordant for early cannabis use. SETTING: General population sample
      of twins (median age, 30 years). PARTICIPANTS: Two hundred seventy-seven same-sex
      twin pairs discordant for cannabis dependence and 311 pairs discordant for early
      onset cannabis use (before age 17 years). MAIN OUTCOME MEASURES: Self-report
      measures of DSM-IV-defined lifetime MDD, suicidal ideation, and suicide attempt.
      RESULTS: Individuals who were cannabis dependent had odds of suicidal ideation
      and suicide attempt that were 2.5 to 2.9 times higher than those of their non
      cannabis-dependent co-twin. Additionally, cannabis dependence was associated with
      elevated risks of MDD in dizygotic but not in monozygotic twins. Those who
      initiated cannabis use before age 17 years had elevated rates of subsequent
      suicide attempt (odds ratio, 3.5 [95% confidence interval, 1.4-8.6]) but not of
      MDD or suicidal ideation. Early MDD and suicidal ideation were significantly
      associated with subsequent risks of cannabis dependence in discordant dizygotic
      pairs but not in discordant monozygotic pairs. CONCLUSIONS: Comorbidity between
      cannabis dependence and MDD likely arises through shared genetic and
      environmental vulnerabilities predisposing to both outcomes. In contrast,
      associations between cannabis dependence and suicidal behaviors cannot be
      entirely explained by common predisposing genetic and/or shared environmental
      predispositions. Previously reported associations between early-onset cannabis
      use and subsequent MDD likely reflect shared genetic and environmental
      vulnerabilities, although it remains possible that early-onset cannabis use may
      predispose to suicide attempt.

PMID- 15466677
TI  - Remission from drug dependence symptoms and drug use cessation among women drug
      users in puerto rico.
AB  - BACKGROUND: Studies of remission from drug dependence have most often been based
      on treatment samples, with limited generalizability to persons who may benefit
      from but never seek substance abuse treatment. Little is known about remission
      patterns among drug users in the community. OBJECTIVE: To identify patterns and
      predictors of remission in a community sample of drug users followed up
      prospectively. DESIGN: Three waves of data on a range of individual and
      interpersonal correlates of drug abuse and health care service use were collected
      between April 1997 and October 2000. SETTING: Areas of metropolitan San Juan
      where drug sales were known to occur. PARTICIPANTS: Two hundred seventy-five
      women aged 18 to 35 who were crack cocaine or injecting drug users. MAIN OUTCOME
      MEASURES: Self-reported drug use validated with urine screens and drug use
      dependence criteria based on the DSM-IV. RESULTS: Most (86.9%) of the women were
      drug dependent at baseline. By wave 3, fewer than half (42.6%) of the women were
      dependent, 13.8% had subthreshold disorder, and 17.8% used substances but did not
      endorse any dependence criteria. Cessation of use and decreases in the number of
      dependence criteria endorsed were significantly less likely for women with
      depressive symptoms (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.88
      0.96; and OR, 0.88; 95% CI, 0.86-0.90; respectively), with a partner who engaged
      in criminal activities (OR, 0.30; 95% CI, 0.16-0.58; and OR, 0.63; 95% CI, 0.46
      0.85; respectively), and who traded sex for money or drugs (OR, 0.12; 95% CI,
      0.05-0.29; and OR, 0.26; 95% CI, 0.19-0.35; respectively). CONCLUSIONS: Drug use
      patterns and rates of dependence fluctuated substantially over time among drug
      users recruited from the community. Findings regarding the characteristics that
      impede remission suggest that mental health practitioners have an important role
      to play in community-based outreach and interventions designed to support women's
      efforts to stop using drugs.

PMID- 15466678
TI  - The Pathways Study: a randomized trial of collaborative care in patients with
      diabetes and depression.
AB  - BACKGROUND: There is a high prevalence of depression in patients with diabetes
      mellitus. Depression has been shown to be associated with poor self-management
      (adherence to diet, exercise, checking blood glucose levels) and high hemoglobin
      A1c (HbA1c) levels in patients with diabetes. OBJECTIVE: To determine whether
      enhancing quality of care for depression improves both depression and diabetes
      outcomes in patients with depression and diabetes. DESIGN: Randomized controlled
      trial with recruitment from March 1, 2001, to May 31, 2002. SETTING: Nine primary
      care clinics from a large health maintenance organization. PARTICIPANTS: A total
      of 329 patients with diabetes mellitus and comorbid major depression and/or
      dysthymia. Intervention Patients were randomly assigned to the Pathways case
      management intervention (n = 164) or usual care (n = 165). The intervention
      provided enhanced education and support of antidepressant medication treatment
      prescribed by the primary care physician or problem-solving therapy delivered in
      primary care. MAIN OUTCOME MEASURES: Independent blinded assessments at baseline
      and 3, 6, and 12 months of depression (Hopkins Symptom Checklist 90), global
      improvement, and satisfaction with care. Automated clinical data were used to
      evaluate adherence to antidepressant regimens, percentage receiving specialty
      mental health visits, and HbA1c levels. RESULTS: When compared with usual care
      patients, intervention patients showed greater improvement in adequacy of dosage
      of antidepressant medication treatment in the first 6-month period (odds ratio
      [OR], 4.15; 95% confidence interval [CI], 2.28-7.55) and the second 6-month
      period (OR, 2.90; 95% CI, 1.69-4.98), less depression severity over time (z =
      2.84, P = .004), a higher rating of patient-rated global improvement at 6 months
      (intervention 69.4% vs usual care 39.3%; OR, 3.50; 95% CI, 2.16-5.68) and 12
      months (intervention 71.9% vs usual care 42.3%; OR, 3.50; 95% CI, 2.14-5.72), and
      higher satisfaction with care at 6 months (OR, 2.01; 95% CI, 1.18-3.43) and 12
      months (OR, 2.88; 95% CI, 1.67-4.97). Although depressive outcomes were improved,
      no differences in HbA1c outcomes were observed. CONCLUSION: The Pathways
      collaborative care model improved depression care and outcomes in patients with
      comorbid major depression and/or dysthymia and diabetes mellitus, but improved
      depression care alone did not result in improved glycemic control.

PMID- 15466679
TI  - For DSM-V, it's the "disorder threshold," stupid.

PMID- 15466681
TI  - Randomized trial of a parent intervention: parents can make a difference in long
      term adolescent risk behaviors, perceptions, and knowledge.
AB  - BACKGROUND: Although numerous interventions have been demonstrated to reduce
      targeted adolescent risk behaviors for brief periods, sustained behavior changes
      covering multiple risk behaviors have been elusive. OBJECTIVE: To determine
      whether a parental monitoring intervention (Informed Parents and Children
      Together [ImPACT]) with and without boosters can further reduce adolescent
      truancy, substance abuse, and sexual risk behaviors and can alter related
      perceptions 24 months after intervention among youth who have all received an
      adolescent risk-reduction intervention, Focus on Kids (FOK). DESIGN: Randomized,
      controlled, 3-celled longitudinal trial. SETTING: Thirty-five low-income, urban
      community sites. PARTICIPANTS: Eight hundred seventeen African American youth
      aged 13 to 16 at baseline. Intervention All youth participated in FOK, an 8
      session, theory-based, small group, face-to-face risk-reduction intervention, 496
      youth and parents received the 1-session ImPACT intervention (a videotape and
      discussion), 238 of the ImPACT youth also received four 90-minute FOK boosters
      delivered in small groups. MAIN OUTCOME MEASURES: Responses at baseline and 24
      months after intervention to a questionnaire assessing risk and protective
      behaviors and perceptions. Analyses used General Linear Modeling, intraclass
      correlation coefficient, analysis of covariance, and multiple comparisons with
      least significant difference test adjustment. RESULTS: After adjusting for the
      intraclass correlation coefficient, 6 of 16 risk behaviors were significantly
      reduced (P< or =.05) among youth receiving ImPACT compared with youth who only
      received FOK (respectively, mean number of days suspended, 0.65 vs 1.17; carry a
      bat as a weapon, 4.1% vs 9.6%; smoked cigarettes, 12.5% vs 22.7%; used marijuana,
      18.3% vs 26.8%; used other illicit drugs, 1.4% vs 5.6%; and, asked sexual partner
      if condom always used, 77.9% vs 64.9%). Four of the 7 theory-based subscales
      reflected significant protective changes among youth who received ImPACT. ImPACT
      did not produce any significant adverse effects on behaviors or perceptions.
      CONCLUSION: A parent monitoring intervention can significantly broaden and
      sustain protection beyond that conferred through an adolescent risk-reduction
      intervention.

PMID- 15466682
TI  - Child neurodevelopmental outcome and maternal occupational exposure to solvents.
AB  - BACKGROUND: Many women of reproductive age are employed in industries involving
      exposure to organic solvents. Animal toxicological studies and human case reports
      demonstrate that high exposure to solvents causes neurodevelopmental toxicity in
      exposed offspring. Data from occupationally exposed women and their children are
      few. OBJECTIVE: To compare the cognitive, language, and motor performance and the
      behavioral achievements of children whose mothers were exposed occupationally to
      organic solvents during pregnancy with those of a matched unexposed control
      group. PARTICIPANTS: Thirty-two pregnant women occupationally exposed to organic
      solvents were recruited during pregnancy and followed up. Their offspring (age
      range, 3-9 years) were tested for cognitive functioning (IQ), language, visual
      motor functioning, and behavioral functioning and were compared with a matched
      unexposed control group that was recruited and tested in a similar manner.
      Examiners were blinded to the exposure status. RESULTS: Mothers occupationally
      exposed to organic solvents did not differ significantly from matched controls in
      demographic variables. After controlling for potential confounding because of
      maternal IQ and maternal education, children exposed in utero to organic solvents
      obtained lower scores on subtests of intellectual, language, motor, and
      neurobehavioral functioning. CONCLUSIONS: In utero exposure to organic solvents
      is associated with poorer performance on some specific subtle measures of
      neurocognitive function, language, and behavior. Reducing exposure in pregnancy
      is merited until more refined risk assessment is possible. Further studies that
      address exposure to specific solvents, dose, and gestational timing of exposure
      are needed.

PMID- 15466683
TI  - Tympanocentesis for the management of acute otitis media in children: a survey of
      Canadian pediatricians and family physicians.
AB  - OBJECTIVE: To evaluate the current knowledge, practice patterns, skills, and
      attitudes of Canadian pediatricians and family physicians regarding the role of
      diagnostic tympanocentesis in the management of acute otitis media in children.
      DESIGN: Survey. SETTING AND PARTICIPANTS: A self-completion questionnaire was
      mailed to a random selection of 302 pediatricians and 196 family physicians
      practicing in hospitals and community settings across Canada in 2002. A second
      questionnaire was sent to those who did not respond to the first mailing. MAIN
      OUTCOME MEASURES: The demographic features of respondents and their attitudes,
      beliefs, and behaviors regarding tympanocentesis for acute otitis media were
      collected via a 2-page questionnaire consisting of open-ended and multiple-choice
      questions. RESULTS: The overall response rate was 56%. Only 4% of pediatricians
      and family physicians surveyed received training in tympanocentesis, and none
      currently perform the procedure. Higher proportions of those who learned to
      perform tympanocentesis graduated from medical school before 1970 and received
      postgraduate training outside of Canada compared with those who did not learn to
      perform tympanocentesis. Pediatricians were more likely than family physicians to
      make referrals to otolaryngologists for tympanocentesis for acute otitis media
      (62% vs 48%; P = .04). CONCLUSIONS: Few Canadian pediatricians and family
      physicians in our survey learned to perform tympanocentesis, and none currently
      perform the procedure. It is not clear whether current practices for
      tympanocentesis in children with acute otitis media are adequate.

PMID- 15466685
TI  - Effect of recent antipyretic use on measured fever in the pediatric emergency
      department.
AB  - OBJECTIVES: To determine the prevalence of recent antipyretic use among febrile
      infants at a pediatric emergency department (ED) and to test the hypothesis that
      recent antipyretic use is associated with lower measured temperatures in the ED.
      METHODS: We prospectively enrolled infants younger than 366 days at a pediatric
      ED. Eligible subjects had a history of fever prior to arrival at the ED or had a
      measured temperature of 38 degrees C or higher at the ED. Research assistants
      collected detailed information about recent use of antipyretic drugs. Peak
      measured temperature prior to arrival at the ED (temperature maximum [Tmax]),
      measured temperature at the ED, defervescence from Tmax to measured ED
      temperature, and rates of diagnostic testing were compared between subjects who
      had or had not been treated with antipyretic medication within the past 6 hours.
      RESULTS: We enrolled 474 infants. Infants treated with an antipyretic medication
      (n = 187) had a significantly higher Tmax and a significantly higher measured ED
      temperature than untreated subjects (n = 287) (P<.001). Treated and untreated
      subjects did not differ in the amount of defervescence from Tmax to measured ED
      temperature (P = .41) unless treated subjects included only those who reportedly
      received therapeutic doses of antipyretic medication within 1 to 5 hours prior to
      arrival at the ED (P = .02). CONCLUSIONS: Although many febrile infants seen in
      the pediatric ED have recently received antipyretics, only a few have received a
      therapeutic dose between 1 and 5 hours prior to arrival. Among febrile infants
      seen in the ED, recent antipyretic use is associated both with a higher reported
      Tmax and with higher measured temperatures at the ED. Patients treated with a
      therapeutic antipyretic dose 1 to 5 hours prior to arrival experience more
      defervescence from their Tmax than untreated subjects.

PMID- 15466684
TI  - Adolescent and young adult women's misunderstanding of the term Pap smear.
AB  - OBJECTIVE: To learn more about young women's understanding of the term Pap smear.
      DESIGN: Self-administered survey. SETTING: UMass Memorial Adolescent Clinic.
      PARTICIPANTS: Female patients 14 years or older (and their mothers when
      available) who visited the clinic between June 10 and August 9, 2002. MAIN
      OUTCOME MEASURES: Accuracy of participants' written definition for the term Pap
      smear and knowledge that a "Pap smear" is a test for cervical cancer and not
      synonymous with a pelvic examination, sexually transmitted disease test,
      pregnancy test, or checkup. RESULTS: Three (2.7%) of the 111 adolescent
      participants provided an accurate definition of the term Pap smear. Sixty-eight
      percent mistakenly believed that a Pap smear was the same as a pelvic
      examination. Age, history of sexual intercourse, and having had a Pap smear
      correlated with a better Pap smear definition rating. CONCLUSIONS: Remarkably few
      patients who participated in this study understood the meaning of the term Pap
      smear. Confusion about gynecologic terms may hinder efforts to enhance compliance
      with sexually transmitted disease and cervical cancer screening. Educational
      initiatives are needed to improve young people's comprehension and to prevent
      misunderstandings about gynecologic care and miscommunication between patients
      and their health care providers.

PMID- 15466686
TI  - Effect of a standardized pharyngitis treatment protocol on use of antibiotics in
      a pediatric emergency department.
AB  - BACKGROUND: Pharyngitis is a common complaint in pediatric patients. If clinical
      parameters are used alone, bacterial pathogens will be wrongly implicated in many
      cases. A nonstandardized approach to the treatment of children with pharyngitis
      in an emergency department setting may lead to inappropriate empirical therapy,
      contribute to increased bacterial resistance, and result in adverse events
      related to the treatment provided. OBJECTIVE: To implement evidence-based
      guidelines for the diagnosis and treatment of children with pharyngitis in an
      emergency department setting and thereby influence practices of prescribing
      antibiotics. DESIGN AND METHODS: An evidence-based guideline for the evaluation
      and treatment of patients with pharyngitis was developed and implemented in our
      emergency department. Preintervention and postintervention patient cohorts were
      identified by a search of the emergency department's clinical repository. A
      medical record review was performed using a standardized data abstraction form
      (history and examination data, diagnostic testing, and therapy provided).
      Treatment decisions were judged as appropriate if the diagnosis of pharyngitis
      caused by group A beta-hemolytic streptococci was based on confirmatory
      microbiological testing rather than on the history and physical examination
      findings alone. RESULTS: We included 443 patients for study (219 preintervention
      and 224 postintervention). In the preintervention group, 97 (44%) of 214 received
      appropriate treatment. In the postintervention group, 204 (91%) of 224 received
      appropriate treatment. CONCLUSION: An evidence-based clinical guideline can
      influence and improve practices of prescribing antibiotics by pediatric emergency
      physicians in a teaching hospital setting.

PMID- 15466687
TI  - Factors influencing the publication of randomized controlled trials in child
      health research.
AB  - BACKGROUND: Publication bias threatens the validity of clinical decisions. The
      root causes are relatively unknown, and there is limited investigation in child
      research literature. OBJECTIVES: To identify factors associated with subsequent
      nonpublication of abstracts presented at the Society for Pediatric Research
      meetings, and to determine the relative importance of the reasons identified for
      nonpublication. DESIGN: A cross-sectional survey was used to ask researchers
      about their reasons for the selective publication of randomized controlled trials
      (RCTs). The authors of 393 RCTs presented at the Society for Pediatric Research
      meetings from 1992 to 1995 were surveyed. A modified Total Design Method for mail
      surveys was used, with a reminder sent to all potential respondents 1 week after
      the initial mailing and full mailings sent to nonrespondents at 3 and 10 weeks
      following the initial mailing. RESULTS: One hundred sixty-six (45%) completed
      surveys were returned, and 119 (72%) abstracts were published as full
      manuscripts. Factors significantly associated with nonpublication identified
      through multiple logistic regression were the respondent's report of scientific
      merit and significance of results. Of the 47 studies that were not published,
      only 8 (17%) had been submitted for publication. Authors of unpublished studies
      identified the following as important reasons for not publishing: not enough time
      (56.4 responded important or very important); trouble with coauthors (28.9); and
      journal unlikely to accept (26.3). CONCLUSIONS: Of the RCTs presented and not
      subsequently published, the majority (83%) were never submitted for publication.
      The most common reason cited by authors for nonpublication was lack of time.

PMID- 15466688
TI  - Sleep behavior in an urban US sample of school-aged children.
AB  - OBJECTIVES: To describe sleep behavior of elementary school-aged children and to
      assess variations by age, sex, and ethnicity. DESIGN, SETTING, AND PARTICIPANTS:
      Cross-sectional analysis of 755 (50% female, 35% ethnic minority) children 8 to
      11 years old from a community-based sample of children participating in a cohort
      study. Sleep and health data were obtained from a child-completed 7-day sleep
      journal and a caregiver-completed health/sleep questionnaire. MAIN OUTCOME
      MEASURE: Mean nightly sleep duration; bedtime 11 pm or later. RESULTS: Mean (SD)
      sleep duration for all children was 9.63 (0.72) hours. Univariate results showed
      a statistically significant decrease in mean sleep duration associated with
      increasing age (P < .001) and male sex (P = .03). At all ages, minority boys
      slept significantly less than nonminority boys and girls and minority girls. The
      shortest covariate-adjusted mean sleep duration was observed among the oldest
      minority boys (9.28 [0.07] hours vs 9.43-9.85 hours in the other age, sex, and
      ethnicity subgroups). Forty-three percent of 10- to 11-year-old minority boys
      reported less than 9 hours nightly sleep vs 5% to 26% of the other age, sex, and
      ethnicity subgroups. After controlling for potential confounding, minority
      children were more likely than nonminority children to have a bedtime of 11 pm or
      later (odds ratio, 4.8; 95% confidence interval, 2.9-8.0). CONCLUSIONS: A
      sizeable proportion of elementary schoolchildren sleep less than the recommended
      9 hours. Across the age range, decreases in sleep time and, in ethnic minorities,
      increasingly delayed bedtimes suggest emerging sleep restriction in
      preadolescents. Observed ethnic differences in sleep behavior highlight the need
      for better understanding of the social and environmental influences encouraging
      these sleep patterns.

PMID- 15466689
TI  - Lung function at age 3 years: effect of pet ownership and exposure to indoor
      allergens.
AB  - OBJECTIVE: To investigate the effect of pet ownership and exposure to indoor
      allergens on lung function in 3-year-old children. DESIGN: Birth cohort study.
      SETTING: Community. PARTICIPANTS: Children recruited prenatally and followed
      prospectively to age 3 years. MAIN OUTCOME MEASURES: Specific airway resistance
      (sRaw) (measured with body plethysmograph) at age 3 years; skin-prick tests; data
      on cat and dog ownership collected prospectively; allergen levels measured in
      dust collected from homes (high exposure defined as mite allergens >2 microg/g in
      mattress, and dog >10 microg/g and cat >8 microg/g allergens on the living room
      floor). RESULTS: There was no effect of cat or dog ownership at birth or age 3
      years on lung function, and no association between lung function and mite, dog,
      or cat allergen exposure. Sensitized children exposed to high levels of
      sensitizing allergen had significantly poorer lung function (n = 49, sRaw
      kiloPascal per second [kPa/s]; geometric mean [GM], 1.20; 95% confidence interval
      [CI], 1.13-1.28) than children who were not sensitized and not exposed (n = 114;
      GM, 1.08; 95% CI, 1.04-1.12); not sensitized, but exposed (n = 282; GM, 1.07; 95%
      CI, 1.05-1.10); or sensitized and not exposed (n = 53; GM, 1.12; 95% CI, 1.06
      1.18; P = .005). In a multivariate model, independent significant associates of
      lung function were maternal and paternal asthma, and the combination of
      sensitization and exposure to sensitizing allergen, with significant interaction
      between them. Lung function was substantially worse in sensitized and highly
      exposed children with both asthmatic parents (GM, 2.23; 95% CI, 1.68-2.97),
      compared with those with neither (GM, 1.09; 95% CI, 1.04-1.16) or just 1 of these
      features. CONCLUSIONS: Pet ownership, sensitization without exposure, or exposure
      in nonsensitized individuals have no effect on lung function. However, the
      combination of specific sensitization and exposure to sensitizing allergen is
      associated with significantly poorer lung function in early life.

PMID- 15466690
TI  - Incidence and risk factors of fall injuries among infants: a study in Greece.
AB  - OBJECTIVE: To assess the incidence of fall injuries among infants in Greece,
      overall and by type of nursery equipment. DESIGN: Review of data from a large
      injury database. SETTING: The Emergency Department Injury Surveillance System in
      Greece. PATIENTS: A total of 2672 injured infants. INTERVENTIONS: Specially
      trained health visitors performed in-person interviews with the children's
      guardians, using a precoded questionnaire. The results of an independent survey
      of 777 mothers of noninjured children younger than 2 years attending the same
      emergency departments were used to allow quantification of the role of specific
      nursery equipment in the causation of infant fall injuries. MAIN OUTCOME
      MEASURES: Annual rate of injury by falling in infants, overall and by cause.
      RESULTS: About 4400 infant fall injuries occur annually in Greece, corresponding
      to an annual incidence rate of 44 injuries per 1000 infants. The incidence of
      falls increases with increasing infant age. A high percentage of severe injuries
      was detected, most of them concussions (14.3%) and fractures (9.4%).
      Approximately 10% of infants with fall-related injuries required hospitalization.
      More than 36% of fall injuries involved nursery equipment. Infant walker use was
      associated with a higher incidence of falls (about 9 per 1000 infant-years), and
      these falls occasionally involved stairs and caused serious injuries. Infant
      bouncers, strollers, and changing tables were all associated with a similar
      incidence of falls (about 4 per 1000 infant-years). CONCLUSIONS: Falls are a
      common cause of serious infant injuries, and nursery equipment is frequently
      involved in the injury-causing event.

PMID- 15466691
TI  - Hepatitis C prevalence in children with perinatal human immunodeficiency virus
      infection enrolled in a long-term follow-up protocol.
AB  - OBJECTIVE: To evaluate the prevalence of hepatitis C virus (HCV) infection in
      children with perinatal human immunodeficiency virus (HIV) infection. DESIGN:
      Cross-sectional substudy. SETTING: Multicenter study from 41 sites in the United
      States. PATIENTS: Children with perinatal HIV infection were randomly selected
      from a large, long-term, follow-up protocol. MAIN OUTCOME MEASURE: Hepatitis C
      infection was defined as having positive test results on both HCV antibody and
      HCV RNA assays. RESULTS: Five hundred thirty children enrolled in the substudy;
      definitive HCV test results were available for 525 children. Eighty-three percent
      were of a minority race or ethnicity. They were equally distributed by sex, had a
      median age of 10.7 years, and were relatively healthy, with 75% having CD4+
      lymphocyte counts greater than 500 cells/mm3. Eight of 525 children (1.5%; 95%
      confidence interval [CI], 0.7%-3.0%) infected with HIV were coinfected with HCV.
      In contrast, the rate of HCV infection in a serosurvey of more than 2700 children
      aged 6 to 11 years from the National Health and Nutrition Examination Survey was
      0.2% (95% CI, 0.04%-0.6%). In our study, there were no differences between
      children coinfected with HIV and HCV and those without HCV infection in terms of
      demographic characteristics, CD4+ or CD8+ T-lymphocyte counts, HIV 1 RNA levels,
      preterm or mode of delivery, or liver disease; however, the number of children
      coinfected with HIV and HCV was small. CONCLUSION: While HCV prevalence infection
      rates are low in children with perinatal HIV infection, they are 8 to 10 times
      higher than reported in HCV serosurveys of children in the United States.

PMID- 15466692
TI  - Breaching the contract: the ethics of nonpublication of research studies.

PMID- 15466693
TI  - Outcomes after "benign" extra-axial fluid.

PMID- 15466694
TI  - Clinical prediction model for influenza.

PMID- 15466695
TI  - Identification of inhibitors of auxin transcriptional activation by means of
      chemical genetics in Arabidopsis.
AB  - Auxin modulates diverse plant developmental pathways through direct
      transcriptional regulation and cooperative signaling with other plant hormones.
      Genetic and biochemical approaches have clarified several aspects of the auxin
      regulated networks; however, the mechanisms of perception and subsequent
      signaling events remain largely uncharacterized. To elucidate unidentified
      intermediates, we have developed a high-throughput screen for identifying small
      molecule inhibitors of auxin signaling in Arabidopsis. Analysis of 10,000
      compounds revealed several potent lead structures that abrogate transcription of
      an auxin-inducible reporter gene. Three compounds were found to interfere with
      auxin-regulated proteolysis of an auxin/indole-3-acetic acid transcription
      factor, and two impart phenotypes indicative of an altered auxin response,
      including impaired root development. Microarray analysis was used to demonstrate
      the mechanistic similarities of the two most potent molecules. This strategy
      promises to yield powerful tools for the discovery of unidentified components of
      the auxin-signaling networks and the study of auxin's participation in various
      stages of plant development.

PMID- 15466696
TI  - Robust in vivo gene transfer into adult mammalian neural stem cells by lentiviral
      vectors.
AB  - Stable genetic modification of adult stem cells is fundamental for both
      developmental studies and therapeutic purposes. Using in vivo marking studies, we
      showed that injection of lentiviral vectors (LVs) into the subventricular zone of
      the adult mouse brain enables efficient gene transfer into long-term self
      renewing neural precursors and steady, robust vector expression in their neuronal
      progeny throughout the subventricular zone and its rostral extension, up to the
      olfactory bulb. By clonal and population analysis in culture, we proved that in
      vivo-marked neural precursors display self-renewal and multipotency, two
      essential characteristics of neural stem cells (NSCs). Thus, LVs efficiently
      target long-term repopulating adult NSCs, and the effect of the initial
      transduction is amplified by the continuous generation of NSC-derived, transduced
      progeny. LVs may thus allow novel studies on NSCs' physiology in vivo, and
      introduction of therapeutic genes into NSCs may allow the development of novel
      approaches for untreatable CNS diseases.

PMID- 15466697
TI  - Darwinian adaptation of proteorhodopsin to different light intensities in the
      marine environment.
AB  - Proteorhodopsin, a retinal-binding protein, represents a potentially significant
      source of light-driven energy production in the world's oceans. The distribution
      of photochemically divergent proteorhodopsins is stratified according to depth.
      Here, we present evidence that such photochemical diversity was tuned by
      Darwinian selection. By using a Bayesian method, we identified sites targeted by
      Darwinian selection and mapped them to three-dimensional models of
      proteorhodopsins. We suggest that spectral fine-tuning results from the combined
      effect of amino acids that directly interact with retinal and those that
      influence the confirmation of the retinal-binding pocket.

PMID- 15466698
TI  - Sigma-1 receptors at galactosylceramide-enriched lipid microdomains regulate
      oligodendrocyte differentiation.
AB  - In the brain, myelin is important in regulating nerve conduction and
      neurotransmitter release by providing insulation at axons. Myelin is a
      specialized yet continuous sheet structure of differentiated oligodendrocytes
      (OLs) that is enriched in lipids, specifically galactosylceramides (GalCer)
      originated at the endoplasmic reticulum (ER). GalCer are known to affect OL
      differentiation. However, the mechanism whereby GalCer affect OL differentiation
      is not well understood. Sigma-1 receptors (Sig-1Rs), shown by us to exist in
      detergent-insoluble lipid microdomains at lipid-enriched loci of ER in NG108
      cells, are important in the compartmentalization/transport of ER-synthesized
      lipids and in cellular differentiation. In this study, we used rat primary
      hippocampal cultures and found that Sig-1Rs form GalCer-enriched lipid rafts at
      ER lipid droplet-like structures in the entire myelin sheet of mature OLs. In rat
      OL progenitors (CG-4 cells), levels of lipid raft-residing Sig-1Rs and GalCer
      increase as cells differentiate. Sig-1Rs also increase in OLs and myelin of
      developing rat brains. Sig-1R, GalCer, and cholesterol are colocalized and are
      resistant to the Triton X-100 solubilization. Treating cells with a Sig-1R
      agonist or targeting Sig-1Rs at lipid rafts by overexpression of Sig-1Rs in CG-4
      cells enhances differentiation, whereas reducing Sig-1Rs at lipid rafts by
      transfection of functionally dominant-negative Sig-1Rs attenuates
      differentiation. Furthermore, Sig-1R siRNA inhibits differentiation. Our findings
      indicate that, in the brain, Sig-1Rs targeting GalCer-containing lipid
      microdomains are important for OL differentiation and that Sig-1Rs may play an
      important role in the pathogenesis of certain demyelinating diseases.

PMID- 15466699
TI  - Specific antigen vaccination to treat autoimmune disease.
AB  - Specific antigen vaccination by administration of the target antigen in aqueous
      solution has resulted in significant decreases of disease severity in animal
      models of experimental allergic encephalomyelitis, type I diabetes, and several
      forms of antigen-induced arthritis, even if administered after the initiation of
      symptoms. However, in experimental autoimmune encephalomyelitis (EAE) and type I
      diabetes in nonobese diabetic (NOD) mice, repeated administration of peptide
      fragments of target antigens in incomplete Freund's adjuvant has resulted in
      severe anaphylactic reactions. Although these methods of administration are known
      to potentiate CD4 T helper 2 (Th2) responses, which is the goal of specific
      antigen vaccination, the risk of anaphylaxis raises a red flag concerning use of
      this therapy for diseases such as type I diabetes, where the survival time after
      onset is quite long. It is clear that specific antigen vaccination is effective
      in preventing several animal models of autoimmune disease, and in treating these
      diseases once the symptoms are overt. However, the risks of this therapy require
      serious consideration of alternative methods for down-regulation of the
      autoimmune process.

PMID- 15466700
TI  - Sphingosine-dependent apoptosis: a unified concept based on multiple mechanisms
      operating in concert.
AB  - Exposure of 3T3/A31 cells to serum-free medium, one type of apoptotic stimulus,
      causes a rapid increase in the sphingosine (Sph) level, which initiates a series
      of processes: (i) activation of caspase 3 through an enhanced "cascade" of
      caspases, (ii) release of the C-terminal-half kinase domain of PKCdelta (PKCdelta
      KD) by caspase 3, and (iii) activation of Sph-dependent kinase 1 (SDK1), which
      was previously identified as PKCdelta KD. The activation of caspase 3 and release
      of PKCdelta KD are inhibited strongly by the incubation of cells with the
      ceramidase inhibitor D-erythro-2-tetradecanoylamino-1-phenyl-1-propanol and, to a
      much lesser extent, by L-cycloserine, an inhibitor of de novo ceramide synthesis.
      Exogenous addition of Sph or N,N-dimethyl-Sph to U937 cells causes caspase 3
      activation and release of PKCdelta KD (SDK1), leading to apoptosis. The Sph
      induced apoptotic process associated with activation of caspase 3 and release of
      PKCdelta KD (SDK1) may promote the proapoptotic effect of BAD or BAX through an
      increase of phosphorylated 14-3-3. In addition, Sph induces apoptosis through a
      separate process: the blocking of "survival signal" through the Akt kinase
      pathway induced by alpha3beta1-mediated cell adhesion to laminin 10/11 in
      extracellular matrix. We hereby propose a unified concept of Sph-dependent
      apoptosis based on these multiple mechanisms operating in concert.

PMID- 15466701
TI  - Formin' new ideas about actin filament generation.

PMID- 15466702
TI  - A comparative analysis of transcribed genes in the mouse hypothalamus and
      neocortex reveals chromosomal clustering.
AB  - The hypothalamus and neocortex are subdivisions of the mammalian forebrain, and
      yet, they have vastly different evolutionary histories, cytoarchitecture, and
      biological functions. In an attempt to define these attributes in terms of their
      genetic activity, we have compared their genetic repertoires by using the Serial
      Analysis of Gene Expression database. From a comparison of 78,784 hypothalamus
      tags with 125,296 neocortical tags, we demonstrate that each structure possesses
      a different transcriptional profile in terms of gene ontological characteristics
      and expression levels. Despite its more recent evolutionary history, the
      neocortex has a more complex pattern of gene activity. Gene identities and levels
      of gene expression were mapped to their chromosomal positions by using in silico
      definition of GC-rich and GC-poor genome bands. This analysis shows contrasting
      views of gene activity on a genome scale that is unique to each brain
      substructure. We show that genes that are more highly expressed in one tissue
      tend to be clustered together on a chromosomal scale, further defining the
      genetic identity of either the hypothalamus or neocortex. We propose that
      physical proximity of coregulated genes may facilitate transcriptional access to
      the genetic substrates of evolutionary selection that ultimately shape the
      functional subdivisions of the mammalian brain.

PMID- 15466703
TI  - An emerging consensus for telomerase RNA structure.

PMID- 15466704
TI  - Distinct endothelial phenotypes evoked by arterial waveforms derived from
      atherosclerosis-susceptible and -resistant regions of human vasculature.
AB  - Atherosclerotic lesion localization to regions of disturbed flow within certain
      arterial geometries, in humans and experimental animals, suggests an important
      role for local hemodynamic forces in atherogenesis. To explore how endothelial
      cells (EC) acquire functional/dysfunctional phenotypes in response to vascular
      region-specific flow patterns, we have used an in vitro dynamic flow system to
      accurately reproduce arterial shear stress waveforms on cultured human EC and
      have examined the effects on EC gene expression by using a high-throughput
      transcriptional profiling approach. The flow patterns in the carotid artery
      bifurcations of several normal human subjects were characterized by using 3D flow
      analysis based on actual vascular geometries and blood flow profiles. Two
      prototypic arterial waveforms, "athero-prone" and "athero-protective," were
      defined as representative of the wall shear stresses in two distinct regions of
      the carotid artery (carotid sinus and distal internal carotid artery) that are
      typically "susceptible" or "resistant," respectively, to atherosclerotic lesion
      development. These two waveforms were applied to cultured EC, and cDNA
      microarrays were used to analyze the differential patterns of EC gene expression.
      In addition, the differential effects of athero-prone vs. athero-protective
      waveforms were further characterized on several parameters of EC structure and
      function, including actin cytoskeletal organization, expression and localization
      of junctional proteins, activation of the NF-kappaB transcriptional pathway, and
      expression of proinflammatory cytokines and adhesion molecules. These global gene
      expression patterns and functional data reveal a distinct phenotypic modulation
      in response to the wall shear stresses present in atherosclerosis-susceptible vs.
      atherosclerosis-resistant human arterial geometries.

PMID- 15466705
TI  - Units of representation in visual word recognition.

PMID- 15466706
TI  - Requirement of c-myb in T cell development and in mature T cell function.
AB  - Previous reports have suggested that the protooncogene c-myb participates in T
      cell development in the thymus and mature T cell proliferation. We have generated
      two T cell-specific c-myb knockout mouse models, myb/LckCre and myb/CD4Cre. We
      have demonstrated that c-myb is required for the development of thymocytes at the
      DN3 stage, for survival and proliferation of double-positive thymocytes, for
      differentiation of single-positive CD4 and CD8 T cells, and for the proliferative
      responses of mature T cells. In addition, our data show that c-myb is directly
      involved in the formation of double-positive CD4+CD8+CD25+, CD4+CD25+, and
      CD8+CD25+ T cells, developmental processes that may imply a role for c-myb in
      autoimmune dysfunction.

PMID- 15466707
TI  - Genomic analysis of Bacteroides fragilis reveals extensive DNA inversions
      regulating cell surface adaptation.
AB  - Bacteroides are predominant human colonic commensals, but the principal
      pathogenic species, Bacteroides fragilis (BF), lives closely associated with the
      mucosal surface, whereas a second major species, Bacteroides thetaiotaomicron
      (BT), concentrates within the colon. We find corresponding differences in their
      genomes, based on determination of the genome sequence of BF and comparative
      analysis with BT. Both species have acquired two mechanisms that contribute to
      their dominance among the colonic microbiota: an exceptional capability to use a
      wide range of dietary polysaccharides by gene amplification and the capacity to
      create variable surface antigenicities by multiple DNA inversion systems.
      However, the gene amplification for polysaccharide assimilation is more developed
      in BT, in keeping with its internal localization. In contrast, external antigenic
      structures can be changed more systematically in BF. Thereby, at the mucosal
      surface, where microbes encounter continuous attack by host defenses, BF evasion
      of the immune system is favored, and its colonization and infectious potential
      are increased.

PMID- 15466708
TI  - Dynamical transition and proteinquake in photoactive yellow protein.
AB  - Conformational dynamics in protein functioning covers a wide range of time scales
      from nanosecond fluctuations around a conformation to the large-amplitude
      conformational changes of milliseconds or longer. We illustrate a picture of
      cooperative coupling among such motions of different time scales in a model
      protein, photoactive yellow protein, by proposing a model that can consistently
      explain the experimental results on the photocycle of photoactive yellow protein.
      The model provides a scenario in which the global collective motion induced by
      the unfolding of the N-terminal domain promotes the loosening of the atomistic
      packing around the chromophore, which produces the favorable molecular
      environment for the photoexcited chromophore, thereby stabilizing the partially
      unfolded intermediate in the photocycle. The proteinquake, the large
      conformational change triggered by the local structural disturbance, plays a
      decisive role in controlling the kinetics of functioning.

PMID- 15466709
TI  - Small interfering RNA targeting Fas protects mice against renal ischemia
      reperfusion injury.
AB  - Fas-mediated apoptosis has been suggested to contribute to tubular cell death
      after renal ischemia-reperfusion injury. Here we investigate whether small
      interfering RNA (siRNA) duplexes targeting Fas protect mice from acute renal
      failure after clamping of the renal artery. Renal ischemia-reperfusion injury was
      induced by clamping the renal vein and artery for 15 or 35 min. Mice were treated
      before or after ischemia with siRNA targeting Fas or a control gene, administered
      by hydrodynamic injection, low-volume renal vein injection, or both. Treated mice
      were evaluated for renal Fas protein and mRNA expression, tissue histopathology,
      and apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP nick end
      labeling (TUNEL) staining. Blood urea nitrogen and survival were monitored in
      mice in which the contralateral kidney had been removed. A single hydrodynamic
      injection of Fas siRNA reduced Fas mRNA and protein expression in the kidney 4
      fold. Kidneys from mice that received Fas siRNA two days earlier had
      substantially less renal tubular apoptosis by TUNEL staining and less tubular
      atrophy and hyaline damage. Whereas 90% of mice pretreated with saline or GFP
      siRNA died, only 20% of Fas-siRNA-pretreated animals died. The same survival
      advantage was provided by a single low-volume Fas siRNA injection into the renal
      vein. Moreover, postischemic injection through the renal vein protected 38% of
      mice from death. This study confirms the importance of Fas-mediated apoptosis in
      renal ischemia-reperfusion injury. Silencing Fas by systemic or local
      catheterization holds therapeutic promise to limit ischemia-reperfusion injury.

PMID- 15466710
TI  - The complete genomic sequence of Nocardia farcinica IFM 10152.
AB  - We determined the genomic sequence of Nocardia farcinica IFM 10152, a clinical
      isolate, and revealed the molecular basis of its versatility. The genome consists
      of a single circular chromosome of 6,021,225 bp with an average G+C content of
      70.8% and two plasmids of 184,027 (pNF1) and 87,093 (pNF2) bp with average G+C
      contents of 67.2% and 68.4%, respectively. The chromosome encoded 5,674 putative
      protein-coding sequences, including many candidate genes for virulence and
      multidrug resistance as well as secondary metabolism. Analyses of paralogous
      protein families suggest that gene duplications have resulted in a bacterium that
      can survive not only in soil environments but also in animal tissues, resulting
      in disease.

PMID- 15466711
TI  - Hidden complexity of free energy surfaces for peptide (protein) folding.
AB  - An understanding of the thermodynamics and kinetics of protein folding requires a
      knowledge of the free energy surface governing the motion of the polypeptide
      chain. Because of the many degrees of freedom involved, surfaces projected on
      only one or two progress variables are generally used in descriptions of the
      folding reaction. Such projections result in relatively smooth surfaces, but they
      could mask the complexity of the unprojected surface. Here we introduce an
      approach to determine the actual (unprojected) free energy surface and apply it
      to the second beta-hairpin of protein G, which has been used as a model system
      for protein folding. The surface is represented by a disconnectivity graph
      calculated from a long equilibrium folding-unfolding trajectory. The denatured
      state is found to have multiple low free energy basins. Nevertheless, the peptide
      shows exponential kinetics in folding to the native basin. Projected surfaces
      obtained from the present analysis have a simple form in agreement with other
      studies of the beta-hairpin. The hidden complexity found for the beta-hairpin
      surface suggests that the standard funnel picture of protein folding should be
      revisited.

PMID- 15466712
TI  - Quantum speciation in Aegilops: molecular cytogenetic evidence from rDNA cluster
      variability in natural populations.
AB  - Data are presented on quantum speciation in the Sitopsis section of the genus
      Aegilops (Poaceae, Monocotyledones). Two small, peripheral, isolated, wild
      populations of annual cross-pollinated Ae. speltoides and annual self-pollinated
      Ae. sharonensis are located 30 m apart on different soil types. Despite the close
      proximity of the two species and their close relatedness, no mixed groups are
      known. Comparative molecular cytogenetic analysis based on the intrapopulation
      variability of rRNA-encoding DNA (rDNA) chromosomal patterns of individual Ae.
      speltoides geno-types revealed an ongoing dynamic process of permanent
      chromosomal rearrangements. Chromosomal mutations can arise de novo and can be
      eliminated. Analysis of the progeny of the investigated genotypes testifies that
      inheritance of de novo rDNA sites happens frequently. Heterologous recombination
      and/or transposable elements-mediated rDNA transfer seem to be the mechanisms for
      observed chromosomal repatterning. Consequently, several modified genomic forms,
      intermediate between Ae. speltoides and Ae. sharonensis, permanently arise in the
      studied wild population of Ae. speltoides, which make it possible to recognize
      Ae. sharonensis as a derivative species of Ae. speltoides, as well as to propose
      rapidness and canalization of quantum speciation in Sitopsis species.

PMID- 15466713
TI  - Synaptic homeostasis and input selectivity follow from a calcium-dependent
      plasticity model.
AB  - Modifications in the strengths of synapses are thought to underlie memory,
      learning, and development of cortical circuits. Many cellular mechanisms of
      synaptic plasticity have been investigated in which differential elevations of
      postsynaptic calcium concentrations play a key role in determining the direction
      and magnitude of synaptic changes. We have previously described a model of
      plasticity that uses calcium currents mediated by N-methyl-D-aspartate receptors
      as the associative signal for Hebbian learning. However, this model is not
      completely stable. Here, we propose a mechanism of stabilization through
      homeostatic regulation of intracellular calcium levels. With this model, synapses
      are stable and exhibit properties such as those observed in metaplasticity and
      synaptic scaling. In addition, the model displays synaptic competition, allowing
      structures to emerge in the synaptic space that reflect the statistical
      properties of the inputs. Therefore, the combination of a fast calcium-dependent
      learning and a slow stabilization mechanism can account for both the formation of
      selective receptive fields and the maintenance of neural circuits in a state of
      equilibrium.

PMID- 15466714
TI  - Astrocytes generate Na+-mediated metabolic waves.
AB  - Glutamate-evoked Na+ increase in astrocytes has been identified as a signal
      coupling synaptic activity to glucose consumption. Astrocytes participate in
      multicellular signaling by transmitting intercellular Ca2+ waves. Here we show
      that intercellular Na+ waves are also evoked by activation of single cultured
      cortical mouse astrocytes in parallel with Ca2+ waves; however, there are spatial
      and temporal differences. Indeed, maneuvers that inhibit Ca2+ waves also inhibit
      Na+ waves; however, inhibition of the Na+/glutamate cotransporters or enzymatic
      degradation of extracellular glutamate selectively inhibit the Na+ wave. Thus,
      glutamate released by a Ca2+ wave-dependent mechanism is taken up by the
      Na+/glutamate cotransporters, resulting in a regenerative propagation of
      cytosolic Na+ increases. The Na+ wave gives rise to a spatially correlated
      increase in glucose uptake, which is prevented by glutamate transporter
      inhibition. Therefore, astrocytes appear to function as a network for concerted
      neurometabolic coupling through the generation of intercellular Na+ and metabolic
      waves.

PMID- 15466715
TI  - Divergence of T2R chemosensory receptor families in humans, bonobos, and
      chimpanzees.
AB  - T2R (Tas2R) genes encode a family of G protein-coupled gustatory receptors,
      several involved in bitter taste perception. So far, few ligands for these
      receptors have been identified, and the specificity of most T2Rs is unclear.
      Differences between individual T2Rs result in altered taste perception in either
      specificity or sensitivity. All 33 human T2Rs are characterized by significant
      sequence homology. However, with a total of eight pseudogenes and >83 coding
      region single-nucleotide polymorphisms, the family displays broad diversity. The
      underlying variability of individual T2Rs might be the source for personalized
      taste perception. To test this hypothesis and also to identify T2Rs that possibly
      function beyond bitter taste, we compared all human T2R genes with those of the
      closely related primate species Pan paniscus (bonobo) and Pan troglodytes
      (chimpanzee). The differences identified range from large sequence alterations to
      nonsynonymous and synonymous changes of single base pairs. In contrast to
      olfactory receptors, no human-specific loss of the amount of functional genes was
      observed. Taken together, the results indicate ongoing evolutionary
      diversification of T2R receptors and a role for T2Rs in dietary adaptation and
      personalized food uptake.

PMID- 15466716
TI  - Broadband relaxation-optimized polarization transfer in magnetic resonance.
AB  - Many applications of magnetic resonance are limited by rapid loss of spin
      coherence caused by large transverse relaxation rates. In NMR of large proteins,
      increased relaxation losses lead to poor sensitivity of experiments and increased
      measurement time. In this article, we develop broadband relaxation-optimized
      pulse sequences that approach fundamental limits of coherence transfer efficiency
      in the presence of very general relaxation mechanisms that include cross
      correlated relaxation. These broadband transfer schemes use techniques of
      chemical shift refocusing (specific trajectory adapted refocusing echoes) that
      are tailored to specific trajectories of coupled spin evolution. We present
      simulations and experimental data indicating significant enhancement in the
      sensitivity of multidimensional NMR experiments of large molecules through these
      methods.

PMID- 15466717
TI  - Fibrillin microfibrils: multipurpose extracellular networks in organismal
      physiology.
AB  - Organismal physiology depends significantly on the proper assembly of
      extracellular matrix (ECM) macroaggregates that impart structural integrity to
      the connective tissue. Recent genetic studies in mice have unraveled unsuspected
      new functions of architectural matrix components in regulating signaling events
      that modulate patterning, morphogenesis, and growth of several organ systems. As
      a result, a new paradigm has emerged whereby tissue-specific organization of the
      ECM dictates not only the physical properties of the connective tissue, but also
      the ability of the matrix to direct a broad spectrum of cellular activities
      through the regulation of growth factor signaling. These observations pave the
      way to novel therapeutic approaches aimed at counteracting the deleterious
      consequences of perturbations of connective tissue homeostasis.

PMID- 15466718
TI  - Large-scale reprogramming of cranial neural crest gene expression by retinoic
      acid exposure.
AB  - Although retinoic acid (RA), the active form of vitamin A, is required for normal
      embryonic growth and development, it is also a powerful teratogen. Infants born
      to mothers exposed to retinoids during pregnancy have a 25-fold increased risk
      for malformations, nearly exclusively of cranial neural crest-derived tissues. To
      characterize neural crest cell responses to RA, we exposed murine crest cultures
      to teratogenic levels of RA and subjected their RNA to microarray-based gene
      expression profile analysis using Affymetrix MG-U74Av2 GeneChips. RNAs were
      isolated from independent cultures treated with 10(-6) M RA for 6, 12, 24, or 48
      h. Statistical analyses of gene expression profile data facilitated
      identification of the 205 top-ranked differentially regulated genes whose
      expression was reproducibly changed by RA over time. Cluster analyses of these
      genes across the independently treated sample series revealed distinctive kinetic
      patterns of altered gene expression. The largest group was transiently affected
      within the first 6 h of exposure, representing early responding genes. Group 2
      showed sustained induction by RA over all times, whereas group 3 was
      characterized by the suppression of a time-dependent expression increase normally
      seen in untreated cells. Additional patterns demonstrated time-dependent
      increased or decreased expression among genes not normally regulated to a
      significant extent. Gene function analysis revealed that more than one-third of
      all RA-regulated genes were associated with developmental regulation, including
      both canonical and noncanonical Wnt signaling pathways. Multiple genes associated
      with cell adhesion and cell cycle regulation, recognized targets for the
      biological effects of RA, were also affected. Taken together, these results
      support the hypothesis that the teratogenic effects of RA derive from
      reprogramming gene expression of a host of genes, which play critical roles
      during embryonic development regulating pathways that determine subsequent
      differentiation of cranial neural crest cells.

PMID- 15466719
TI  - Legg-Calve-Perthes disease. Part I: Classification of radiographs with use of the
      modified lateral pillar and Stulberg classifications.
AB  - BACKGROUND: Accurate and reliable radiographic classifications of the relative
      severity and outcome of Legg-Calve-Perthes disease are essential in the study of
      that disease. As part of a prospective multicenter study, we sought to define
      more clearly the lateral pillar classification of severity and the Stulberg
      classification of outcome; we sought especially to define the borderlines between
      classification groups. METHODS: We performed interobserver and intraobserver
      trials of the lateral pillar and Stulberg classifications using sets of twenty
      radiographs chosen from a prospective study of 345 hips. To establish reliable
      definitions of the lateral pillar classification, we added a new, intermediate
      group termed the B/C border group, which includes femoral heads with a thin or
      poorly ossified lateral pillar and those with a loss of exactly 50% of the
      original height of the lateral pillar. The resulting classification consists of
      four groups: A, B, B/C border, and C. In our application of the classification
      system of Stulberg et al., we defined a class-II femoral head as round and
      fitting within 2 mm of a circle on both anteroposterior and frog-leg lateral
      radiographs. We defined a Stulberg class-III femoral head as out of round by more
      than 2 mm on either view and a Stulberg class-IV femoral head as one with at
      least 1 cm of flattening of the weight-bearing articular surface. To assess
      interobserver and intraobserver agreement, we performed two trials of each
      classification with six orthopaedic surgeons reviewing twenty radiographs or
      pairs of radiographs. RESULTS: In the first trial of the lateral pillar
      classification, there was 81% agreement per radiograph and the average weighted
      kappa was 0.71. In the second trial, there was 85% agreement per radiograph and
      the weighted kappa averaged 0.79. Intraobserver reliability testing showed a 77%
      match between Trials 1 and 2, an average weighted kappa of 0.81, and an average
      generalizability coefficient of 0.91. In Trial 1 of the Stulberg classification,
      there was 91% agreement per radiograph and an average weighted kappa of 0.82. In
      Trial 2, there was 92% agreement per radiograph and an average weighted kappa of
      0.82. Intraobserver reliability testing showed an 89% match between Trials 1 and
      2, an average weighted kappa value of 0.88, and an average generalizability
      coefficient of 0.92. CONCLUSIONS: The interobserver and intraobserver trials of
      these classifications produced kappa values and generalizability coefficients in
      the excellent range. The modified lateral pillar classification and the redefined
      Stulberg classification are sufficiently reliable and accurate for use in studies
      of Legg-Calve-Perthes disease.

PMID- 15466720
TI  - Legg-Calve-Perthes disease. Part II: Prospective multicenter study of the effect
      of treatment on outcome.
AB  - BACKGROUND: The treatment of Legg-Calve-Perthes disease has been based on
      uncontrolled retrospective studies with relatively small numbers of patients.
      This large, controlled, prospective, multicenter study was designed to determine
      the effect of treatment and other risk factors on the outcome in patients with
      this disorder. METHODS: We enrolled 438 patients with 451 affected hips in a
      prospective multicenter study in which each investigator applied the same
      treatment method to each of his or her patients. The five treatment groups
      consisted of no treatment, brace treatment, range-of-motion exercises, femoral
      osteotomy, and innominate osteotomy. All patients were between 6.0 and 12.0 years
      of age at the onset of the disease, and none had had prior treatment. Three
      hundred and forty-five hips in 337 patients were available for follow-up at
      skeletal maturity. All hips were classified with the modified lateral pillar
      classification and the system of Stulberg et al. RESULTS: There were no
      differences in outcome among the hips with no treatment, those treated with
      bracing, and those treated with range-of-motion therapy. There were also no
      differences between the hips treated with a femoral varus osteotomy and those
      treated with an innominate osteotomy. Treatment did not have a significant effect
      on children who had a chronologic age of 8.0 years or less or a skeletal age of
      6.0 years or less at the onset of the disease. In the lateral pillar B group and
      B/C border group, the outcomes of surgical treatment were significantly better
      than those of nonoperative treatment in children over the age of 8.0 years at the
      onset of the disease (p < or = 0.05). Patients who were 8.0 years old or less at
      the onset of the disease in lateral pillar group B did equally well with
      nonoperative and operative treatment. Hips in lateral pillar group C had the
      least favorable outcomes, with no differences between the operative and
      nonoperative groups. The lateral pillar classification (p < 0.0001) and the age
      at the onset of the disease (p = 0.0001) were both strong prognostic factors.
      Female patients did significantly worse than male patients if they were over the
      age of 8.0 years at the onset of the disease (p = 0.004). CONCLUSIONS: The
      lateral pillar classification and age at the time of onset of the disease
      strongly correlate with outcome in patients with Legg-Calve-Perthes disease.
      Patients who are over the age of 8.0 years at the time of onset and have a hip in
      the lateral pillar B group or B/C border group have a better outcome with
      surgical treatment than they do with nonoperative treatment. Group-B hips in
      children who are less than 8.0 years of age at the time of onset have very
      favorable outcomes unrelated to treatment, whereas group-C hips in children of
      all ages frequently have poor outcomes, which also appear to be unrelated to
      treatment.

PMID- 15466721
TI  - Determining the relationship of the axillary nerve to the shoulder joint capsule
      from an arthroscopic perspective.
AB  - BACKGROUND: The axillary nerve is out of the field of view during shoulder
      arthroscopy, but certain procedures require manipulation of capsular tissue that
      can threaten the function or integrity of the nerve. We studied fresh cadavers to
      identify the course of the axillary nerve in relation to the glenoid rim from an
      intra-articular perspective and to determine how close the nerve travels in
      relation to the glenoid rim and the inferior glenohumeral ligament. METHODS: We
      dissected nine whole-body fresh-tissue shoulder joints and exposed the axillary
      nerve through a window in the inferior glenohumeral ligament. Then we cut coronal
      sections through the glenoid fossa of ten unembalmed, frozen shoulder specimens
      after the axillary nerve had been stained with Evans blue dye. All specimens were
      studied with the joint secured in the lateral decubitus position used for
      shoulder arthroscopy. RESULTS: Microsurgical dissection through the inferior
      glenohumeral ligament from within the joint capsule revealed the axillary nerve
      as it traversed the quadrangular space. In each dissection, the teres minor
      branch was the closest to the glenoid rim. The coronal sectioning of the
      unembalmed shoulder specimens demonstrated that the closest point between the
      axillary nerve and the glenoid rim was at the 6 o'clock position on the inferior
      glenoid rim. At this position, the average distance between the axillary nerve
      and the glenoid rim was 12.4 mm. The axillary nerve lay, throughout its course,
      at an average of 2.5 mm from the inferior glenohumeral ligament. CONCLUSIONS: We
      used two novel approaches to map the axillary nerve from an intra-articular
      perspective. Our analysis of the position of the nerve with use of these methods
      provides the shoulder arthroscopist with essential information regarding the
      location, route, and morphology of the nerve as it passes inferior to the glenoid
      rim and shoulder capsule.

PMID- 15466722
TI  - Anterior cruciate ligament reconstruction: bone-patellar tendon-bone compared
      with double semitendinosus and gracilis tendon grafts. A prospective, randomized
      clinical trial.
AB  - BACKGROUND: The choice of graft for anterior cruciate ligament reconstruction is
      a matter of debate, with patellar and hamstring tendons being the two most
      popular autologous graft options. The objective of this study was to determine in
      a prospective, randomized clinical trial whether two grafts (bone-patellar tendon
      bone or doubled hamstring tendons) fixed with modern devices affect the two-year
      minimum clinical and radiographic outcomes of anterior cruciate ligament
      reconstruction. METHODS: One hundred and twenty patients with a chronic
      unilateral rupture of the anterior cruciate ligament underwent arthroscopically
      assisted reconstruction with use of either autologous bone-patellar tendon-bone
      or doubled hamstring tendon grafts, in a strictly alternating manner. Both groups
      were comparable with regard to demographic data, preoperative activity level,
      mechanism of injury, interval between the injury and the operation, and the
      amount of knee laxity present preoperatively. The same well-proven surgical
      technique and aggressive controlled rehabilitation was used. An independent
      observer, who was blinded with regard to the involved leg and the type of graft,
      performed the outcome assessment with use of a visual analog scale, the new
      International Knee Documentation Committee form, the Knee Injury and
      Osteoarthritis Outcome Score, the Functional Knee Score for Anterior Knee Pain,
      and an arthrometric and an isokinetic dynamometric evaluation. Radiographs were
      also made. RESULTS: At the two-year follow-up evaluation, no differences were
      found in terms of the visual analog score, the Knee Injury and Osteoarthritis
      Outcome Score, the new International Knee Documentation Committee subjective and
      objective evaluation scores, the KT-1000 side-to-side laxity measurements, the
      Functional Knee Score for Anterior Knee Pain, muscle strength recovery, or return
      to sports activities. In the bone-patellar tendon-bone group, we found a higher
      prevalence of postoperative kneeling discomfort (p < 0.01) and an increased area
      of decreased skin sensitivity (p < 0.001). In the hamstring tendon group, we
      recorded a higher prevalence of femoral tunnel widening (p < 0.01). In this
      group, a correlation was also found between medial meniscectomy and an increased
      prevalence of pivot-shift glide (p = 0.035). CONCLUSIONS: We believe that, with
      use of accurate and proven surgical and rehabilitation techniques, both grafts
      are an equivalent option for anterior cruciate ligament reconstruction.

PMID- 15466723
TI  - Uncemented rotating-platform total knee replacement: a five to twelve-year follow
      up study.
AB  - BACKGROUND: Mobile-bearing knee designs represent an alternative to conventional
      fixed-bearing total knee arthroplasty. We present the results of a prospective,
      intermediate-term clinical follow-up study of the bicruciate ligament-sacrificing
      porous-coated Low Contact Stress rotating-platform total knee design. METHODS:
      Between February 1984 and January 1994, 528 uncemented primary knee replacements
      were performed in 421 patients. All patellae were resurfaced with use of the Low
      Contact Stress rotating patellar component. The average age of the patients at
      the time of the index procedure was sixty-nine years. The study group included
      261 women and 160 men. Patients were evaluated at three months, six months, and
      yearly thereafter with use of the 100-point New Jersey Orthopaedic Hospital knee
      scoring system. In addition, a radiographic analysis of the tibial, femoral, and
      patellar components was performed at each interval. RESULTS: There were twenty
      nine failures that resulted in revision. The Kaplan-Meier estimate of implant
      survival at twelve years was 89.5% (95% confidence interval, 83.4% to 95.6%). The
      total clinical scores improved significantly compared with the preoperative
      scores for the first twelve months postoperatively and then plateaued. Three
      hundred and twenty-one knees had adequate radiographic follow-up (average, 8.1
      years; range, five to twelve years). Zonal radiographic analysis revealed ninety
      three instances of radiolucent lines (eighty-two of which measured <1 mm in
      width), with the greatest number of radiolucent lines (thirty-nine) being located
      around the tibial tray stem. None of these lines were deemed to be progressive,
      and no knee with a radiolucent line that measured >2 mm was revised because of
      failure. CONCLUSIONS: This first-generation uncemented, mobile-bearing,
      bicruciate ligament-sacrificing knee replacement was associated with a good
      survival rate and demonstrated clinical efficacy during the five to twelve-year
      follow-up interval. .

PMID- 15466724
TI  - Neonatal brachial plexus palsy. Outcome of absent biceps function at three months
      of age.
AB  - BACKGROUND: An important prognostic factor in neonatal brachial plexus palsy is
      the time interval to biceps muscle recovery. Although the natural history is not
      clear, biceps muscle recovery after more than three months of age has been used
      to predict poor long-term shoulder function. The absence of biceps muscle
      function at three months of age has been adopted as an indication for early
      brachial plexus microsurgery, in an attempt to improve recovery. To provide a
      benchmark for outcome comparison, the long-term outcome of patients with absent
      biceps muscle function at three months of age was studied. METHODS: Between 1980
      and 1992, 170 patients with neonatal brachial plexus palsy were entered into a
      prospective study in which details of the birth and serial clinical examinations
      were recorded. Patients were grouped according to the level of injury and the
      time interval to biceps muscle recovery. Twenty-nine patients were observed to
      have absent biceps muscle function at three months of age. Twenty-eight of those
      patients were available for long-term followup at a mean age of eleven years and
      one month. At the time of follow-up, patients answered a questionnaire and
      underwent manual muscle strength testing, sensory evaluation, and grading of
      their shoulder function according to Gilbert's modification of the Mallet score,
      in which the function was graded as II, III, or IV with class I (no function) and
      V (normal) eliminated. The level of injury and the time that biceps muscle
      function returned were compared with the final outcomes. RESULTS: The level of
      injury was C5-C6 in thirteen (46%) of our twenty-eight patients with absent
      biceps muscle function at three months of age, C5-C7 in five (18%), and pan
      plexus (C5-T1) in ten (36%). Biceps contraction was observed by six months of age
      in twenty patients (71%), including all thirteen patients with a C5-C6 level of
      injury. Twenty-two patients did not have surgery on the brachial plexus, but nine
      of those patients had subsequent orthopaedic procedures. At the time of follow
      up, twenty-seven of the twenty-eight patients had at least antigravity biceps
      muscle function. Patients who regained biceps muscle function between three and
      six months of age had better scores for abduction (p = 0.04) and for hand-to-neck
      (p = 0.05) and hand-to-back (p < 0.001) function than did patients who regained
      biceps muscle function after six months of age. Patients with a C5-C6 lesion had
      better scores for external rotation (p = 0.04) and for hand-to-neck (p = 0.05),
      hand-to-mouth (p < 0.01), and hand-to-back (p < 0.001) function than did patients
      with a pan-plexus lesion. Twelve (55%) of the twenty-two patients who did not
      have brachial plexus surgery had a class-IV shoulder (good function) according to
      the modified Mallet score. Of the twelve patients with a C5-C6 level of injury
      who did not have brachial plexus surgery, eight had a class-IV shoulder.
      CONCLUSIONS: This study indicated associations between prolonged neurological
      recovery and a more extensive level of injury and worse long-term shoulder
      function. Patients with a C5-C6 injury and absent biceps muscle function at three
      months of age often have good long-term shoulder function without brachial plexus
      surgery.

PMID- 15466725
TI  - Stress examination of supination external rotation-type fibular fractures.
AB  - BACKGROUND: Deltoid incompetence in association with an isolated fibular fracture
      is assumed to be present if there is medial tenderness, ecchymosis, or
      substantial swelling. We sought to determine whether these soft-tissue indicators
      predict deltoid incompetence by comparing such findings with the findings on
      stress radiographs. METHODS: Over a thirty-two-month period, 138 patients who
      presented acutely with a Weber type-B supination-external rotation (SE) fibular
      fracture were evaluated for tenderness (in nine locations), ecchymosis, and
      swelling. Patients who presented with an apparently isolated fibular fracture and
      an intact ankle mortise (with a medial clear space of < or =4 mm and no talar
      subluxation) were evaluated with a stress radiograph to determine deltoid
      competence. Four groups of patients were identified: those who had an SE2
      fracture (defined as those who had a stable ankle on the stress radiograph),
      those who had a stress (+) SE4 fracture (defined as those who had an unstable
      ankle on the stress radiograph), those who had an SE4 fracture (defined as those
      who presented with a wide medial clear space), and those who had a bimalleolar
      fracture. These four groups were compared with regard to tenderness, swelling,
      and ecchymosis at the time of initial presentation. Patients with SE2 injuries
      were allowed immediate weight-bearing. RESULTS: Of the ninety-seven patients who
      presented with an isolated fibular fracture and an intact mortise, sixty-one had
      a stable SE2 injury and thirty-six had an unstable stress (+) SE4 injury. All
      stable SE2 injuries healed with an intact mortise. Medial tenderness, ecchymosis,
      and swelling were not predictive of deltoid incompetence (instability).
      CONCLUSIONS: Stress radiographs allow for the accurate diagnosis of deltoid
      incompetence in patients with Weber type-B SE fibular fractures and no other
      osseous injury. Soft-tissue indicators are not accurate predictors of
      instability. If medial tenderness, ecchymosis, and swelling are used as operative
      indications, in some cases surgery may be performed on stable ankles.

PMID- 15466727
TI  - Indications for magnetic resonance imaging in presumed adolescent idiopathic
      scoliosis.
AB  - BACKGROUND: The use of magnetic resonance imaging has led to the diagnosis of
      abnormalities of the central nervous system associated with apparent idiopathic
      scoliosis. The indications for magnetic resonance imaging for presumed adolescent
      idiopathic scoliosis have not been established. METHODS: One thousand, two
      hundred and eighty children with presumed adolescent idiopathic scoliosis were
      evaluated over a ten-year period. Magnetic resonance imaging of the central
      nervous system (brainstem and spinal cord) was performed for specific patients,
      on the basis of the presence of selected indicators determined from the clinical
      history, physical examination, and plain radiographic examination of the spine.
      The medical records were reviewed to determine the specific indicators, the
      results of the imaging studies, and the subsequent treatment. RESULTS: Magnetic
      resonance imaging was ordered for 274 (21%) of the 1280 children who were
      evaluated. Abnormal findings were seen in twenty-seven (10%) of the 274 patients
      who underwent imaging, or 2% of the entire cohort. The most valuable single
      indicator of an abnormal finding on magnetic resonance imaging was absence of
      thoracic apical segment lordosis: eight of thirty-nine patients with that
      indicator had an abnormal finding on magnetic resonance imaging. The optimal
      diagnostic yield for a single category of indicators occurred when an atypical
      curve pattern was the only indicator: six of fifty-eight patients in whom this
      was the case had an abnormal finding on magnetic resonance imaging. None of the
      twenty children in whom pain was the only indicator category had an abnormal
      imaging study. The optimal diagnostic yield occurred when both an atypical curve
      pattern and neurological indicators were present: thirteen (25%) of fifty-three
      patients in whom this was the case had an abnormal finding on magnetic resonance
      imaging. Thirteen of the twenty-seven patients received surgical treatment for
      the abnormality of the central nervous system revealed by the imaging.
      CONCLUSIONS: The correct use of diagnostic tests is an important component of
      effective medical practice. An abnormality of the central nervous system is
      present in approximately 10% of patients with presumed adolescent idiopathic
      scoliosis in whom only subtle abnormalities are identified on the basis of the
      clinical history, physical examination, or radiographic examination. Knowledge of
      the diagnostic value of the specific clinical indicators, considered individually
      and in combination, can help the clinician to determine more effectively when
      advanced imaging of the central nervous system should be performed.

PMID- 15466726
TI  - Predicting the outcome of total knee arthroplasty.
AB  - BACKGROUND: The relief of pain and the restoration of functional activities are
      the main outcomes of primary total knee arthroplasty for the treatment of
      osteoarthritis. This paper examines the preoperative predictors of pain and
      functional outcome at one and two years following total knee arthroplasty.
      METHODS: Patients were recruited for a prospective observational study of primary
      total knee arthroplasty for the treatment of osteoarthritis from centers in the
      United States, the United Kingdom, and Australia. Research assistants recruited
      the patients and collected the clinical history and physical examination data
      preoperatively and at three, twelve, and twenty-four months postoperatively. The
      Western Ontario and McMaster University Osteoarthritis Index (WOMAC), Short Form
      36 (SF-36), and demographic data were obtained by self-administered patient
      questionnaires. RESULTS: We recruited 860 patients and obtained one-year WOMAC
      data on 759 patients (88%) and two-year data on 701 (82%). The mean age was
      seventy years, and 59% of the patients were female. Using hierarchical regression
      models, we found that the most significant preoperative predictors of worse
      scores on the pain and function domains of the WOMAC scale and on the physical
      functioning domain of the SF-36 at one and two years postoperatively were low
      preoperative scores, a higher number of comorbid conditions, and a low SF-36
      mental health score. After adjusting for these predictors, we found that the
      functional status of the patients from the United Kingdom was significantly worse
      than that of the patients from the other countries and the difference was
      clinically important at both the one-year and two-year follow-up examination (p <
      0.0005). The mean WOMAC pain scores for the three countries were not
      significantly different at one year, and, although they were significantly
      different at two years (p = 0.025), the difference was not clinically important.
      CONCLUSIONS: Patients who have marked functional limitation, severe pain, low
      mental health score, and other comorbid conditions before total knee arthroplasty
      are more likely to have a worse outcome at one year and two years
      postoperatively. After adjusting for these predictors, it was found that patients
      from the United Kingdom had significantly worse functional outcomes but similar
      pain relief compared with those from the United States and Australia.

PMID- 15466728
TI  - The association of radial deficiency with thumb hypoplasia.
AB  - BACKGROUND: Congenital longitudinal deficiencies of the radius and thumb are
      known to be associated with one another; however, the details of their
      relationship are unknown. The purpose of this study was to determine whether
      increased severity of radial deficiencies is associated with increased severity
      of thumb deficiencies and to review the relationship between radial deficiency
      and reconstructibility of a hypoplastic thumb. METHODS: Radiographs and charts of
      227 affected upper extremities of 139 patients with radial longitudinal
      deficiency were reviewed. The associated thumb deficiency was classified
      according to a modification of the Blauth and Schneider-Sickert scheme and the
      radial deficiency was classified according to a modification of the Bayne and
      Klug criteria for 191 extremities of 119 patients. RESULTS: The severity of the
      thumb deficiency was directly proportional to the severity of the radial
      deficiency (p < 0.0001). Half of the extremities had either a thumb deficiency or
      thumb and carpal deficiencies without radial deficiency. Two-thirds (sixty-three)
      of the ninety-five limbs with a normal radius had a thumb that could be
      surgically reconstructed. Seventy-one (91%) of seventy-eight extremities with a
      thumb amenable to surgical reconstruction had a radius that did not require
      surgical reconstruction. All extremities with a radial and/or carpal deficiency
      had a thumb deficiency. Forty-eight (94%) of fifty-one extremities with complete
      absence of the radius had a thumb that was not reconstructible. CONCLUSIONS: This
      study supports the growing body of evidence that the components of radial
      longitudinal deficiency represent a progressive spectrum of upper extremity
      abnormalities, and a distal progression of severity, with distal structures
      likely to be more involved than proximal structures.

PMID- 15466729
TI  - A constrained liner cemented into a secure cementless acetabular shell.
AB  - BACKGROUND: Constrained acetabular components have been used to treat hips with
      recurrent instability following total hip arthroplasty and hips that demonstrate
      instability during revision surgery. In such hips, when a secure cementless
      acetabular shell is present, the surgeon can cement a constrained liner into the
      existing shell. The purpose of this study was to evaluate the clinical and
      radiographic outcome of this technique with use of a tripolar constrained liner
      that was cemented into a well-fixed cementless acetabular shell. METHODS: Between
      1988 and 2000, constrained liners were cemented into thirty-one well-fixed
      cementless acetabular shells at three centers. The average age of the patients at
      the time of the index surgery was 72.1 years, and the indications for the
      procedure were recurrent hip instability in sixteen hips and intraoperative
      instability in fifteen hips. The patients were evaluated with respect to the
      clinical outcome and radiographic evidence of shell loosening and osteolysis.
      RESULTS: At an average duration of follow-up of 3.9 years, twenty-nine liners
      (94%) were securely fixed in the cementless shells and two constrained liners had
      failed. One liner failed because it separated from the cement, and one failed
      because of fracture of the capturing mechanism. Both hips were successfully
      revised with another cemented tripolar constrained liner. No acetabular component
      demonstrated radiographic evidence of progressive loosening or osteolysis.
      CONCLUSIONS: A constrained tripolar liner cemented into a secure, well-positioned
      cementless acetabular shell provides stability and durability at short-term
      follow-up. Careful attention to the preparation of the liner, the sizing of the
      component, and the cementing technique are likely to reduce the failure of this
      construct, which can be used for difficult cases of total hip instability.

PMID- 15466730
TI  - Rotator cuff repair in patients fifty years of age and younger.
AB  - BACKGROUND: Currently, there is no information on the long-term results of
      rotator cuff repair in young patients. The purpose of the present study was to
      determine the results, the risk factors for an unsatisfactory outcome, and the
      rates of failure of this procedure in patients fifty years of age and younger.
      METHODS: Thirty-two patients (thirty-six shoulders) who were fifty years of age
      or younger underwent repair of a full-thickness rotator cuff tear between 1976
      and 1987. Seven patients (seven shoulders) died after less than thirteen years of
      follow-up. The remaining twenty-nine shoulders, which had been followed for a
      minimum of thirteen years or until revision surgery, were included in the
      analysis. The most recent follow-up was performed in the clinic for five
      shoulders and by means of a questionnaire for twenty-four shoulders. RESULTS:
      There were three small, fifteen medium, six large, and five massive tears.
      Rotator cuff repair was associated with significant long-term pain relief (p =
      0.0001). However, there was no significant long-term improvement in active
      abduction or external rotation. Postoperative pain, active abduction, and
      external rotation did not vary significantly according to gender, tear size,
      repair type, or whether a distal clavicular excision had been performed. There
      were eleven excellent, five satisfactory, and thirteen unsatisfactory results.
      Seven shoulders had additional surgery for the treatment of a recurrent tear
      (five), instability (one), or osteoarthritis (one). Three of the five repairs
      that were done for the treatment of a recurrent tear were performed ten years or
      more after the time of the index procedure. CONCLUSIONS: Rotator cuff repair in
      young patients is associated with long-term pain relief. However, this procedure
      is not associated with significant long-term improvement in motion, and a large
      proportion of patients have an unsatisfactory long-term result. The results of
      rotator cuff repair in young patients appear to be less favorable than those in a
      mixed-age population.

PMID- 15466731
TI  - Electrohydraulic high-energy shock-wave treatment for chronic plantar fasciitis.
AB  - BACKGROUND: Plantar fasciitis is a common foot disorder that may be resistant to
      nonoperative treatment. This study evaluated the use of electrohydraulic high
      energy shock waves in patients who failed to respond to a minimum of six months
      of antecedent nonoperative treatment. METHODS: A randomized, placebo-controlled,
      multiply blinded, crossover study was conducted. Phase 1 consisted of twenty
      patients who were nonrandomized to treatment with extracorporeal shock waves to
      assess the phase-2 study protocol. In phase 2, 293 patients were randomized and
      an additional seventy-one patients were nonrandomized. Following ankle-block
      anesthesia, each patient received 100 graded shocks starting at 0.12 to 0.22
      mJ/mm(2), followed by 1400 shocks at 0.22 mJ/mm(2) with use of a high-energy
      electrohydraulic shock-wave device. Patients in the placebo group received
      minimal subcutaneous anesthetic injections and nontransmitted shock waves by the
      same protocol. Three months later, patients were given the opportunity to
      continue without further treatment or have an additional treatment. This allowed
      a patient in the active treatment arm to receive a second treatment and a patient
      who received the placebo to cross over to the active treatment arm. Patients were
      followed at least one year after the final treatment. RESULTS: Treatment was
      successful in seventeen of the twenty phase-1 patients at three months. This
      improved to nineteen (95%) of twenty patients at one year and was maintained at
      five years. In phase 2, three months after treatment, sixty-seven (47%) of the
      144 actively treated patients had a completely successful result compared with
      forty-two (30%) of the 141 placebo-treated patients (p = 0.008). At one year,
      sixty-five of the sixty-seven actively treated, randomized patients maintained a
      successful result. Thirty-six (71%) of the remaining fifty-one nonrandomized
      patients had a successful result at three months. For all 289 patients who had
      one or more actual treatments, 222 (76.8%) had a good or excellent result. No
      patient was made worse by the procedure. CONCLUSIONS: The application of
      electrohydraulic high-energy shock waves to the heel is a safe and effective
      noninvasive method to treat chronic plantar fasciitis, lasting up to and beyond
      one year.

PMID- 15466732
TI  - Open reduction and stable fixation of isolated, displaced talar neck and body
      fractures.
AB  - BACKGROUND: The purpose of this retrospective review was to evaluate the long
      term results of surgical treatment of isolated, displaced talar neck and/or body
      fractures with stable internal fixation. METHODS: The study included twenty-five
      patients with a total of twenty-six displaced fractures isolated to the talus
      that had been treated with open reduction and stable internal fixation and
      followed for a minimum of forty-eight months after the injury. The final follow
      up examination included standard radiographs, computed tomography, and a clinical
      evaluation. Variables that were analyzed included wound type, fracture type,
      Hawkins type, comminution, timing of the surgical intervention, surgical
      approach, quality of fracture reduction, Hawkins sign, osteonecrosis, union, time
      to union, posttraumatic arthritis, and the AOFAS scores including subscores
      (pain, function, and alignment). RESULTS: The average duration of follow-up was
      seventy-four months. Surgical intervention resulted in sixteen fractures with an
      anatomic reduction, five with a nearly anatomic reduction, and five with a poor
      reduction. All eight noncomminuted fractures were anatomically reduced. The
      overall union rate was 88%. All closed, displaced talar neck fractures healed,
      regardless of the time delay until surgical intervention. Posttraumatic arthritis
      of the subtalar joint was the most common finding and was seen in all patients,
      sixteen of whom had involvement of more than one joint. Osteonecrosis was a
      common finding, seen after thirteen of the twenty-six fractures overall and after
      six of the seven open fractures. CONCLUSIONS: Open reduction and internal
      fixation is recommended for the treatment of displaced talar neck and/or body
      fractures. A delay in surgical fixation does not appear to affect the outcome,
      union, or prevalence of osteonecrosis. Posttraumatic arthritis is a more common
      complication than osteonecrosis following operative treatment. Patients with a
      displaced fracture of the talus should be counseled that posttraumatic arthritis
      and chronic pain are expected outcomes even after anatomic reduction and stable
      fixation. This is especially true following open fractures.

PMID- 15466733
TI  - Effect of distal humeral varus deformity on strain in the lateral ulnar
      collateral ligament and ulnohumeral joint stability.
AB  - BACKGROUND: Recent reports have implicated cubitus varus deformity as a risk
      factor for the development of late posterolateral rotatory instability of the
      elbow. The purpose of this study was to determine the biomechanical relationship
      between cubitus varus and strain in the lateral ulnar collateral ligament and
      subluxation of the ulnohumeral joint as it relates to posterolateral rotatory
      instability. METHODS: Eleven fresh-frozen cadaveric elbow joints were mounted in
      an apparatus that allowed active elbow motion. Supracondylar osteotomies were
      performed to create cubitus varus deformities of 0 degrees to 30 degrees in 5
      degrees increments. Each elbow was loaded with a supination moment of 1.2 Nm and
      a resistive triceps extension force. Strain in the lateral ulnar collateral
      ligament and widening of the ulnohumeral joint were measured at each position of
      varus, and the resulting strain and joint-widening values were averaged. RESULTS:
      Strain in the lateral ulnar collateral ligament was found to increase as the
      cubitus varus deformity increased. Likewise, the ulnohumeral joint space was seen
      to progressively widen with increasing cubitus varus. Strain was significantly
      increased at 30 degrees of varus deformity (p = 0.03), and widening of the
      ulnohumeral joint space was significantly increased at 25 degrees of varus
      deformity (p = 0.004). When differences in the size of the cadaveric specimens
      were accounted for in an analysis of covariance, ligament strain was
      significantly increased at 25 degrees of varus (p = 0.005) and widening of the
      ulnohumeral joint space, at 20 degrees (p = 0.01). CONCLUSIONS: Cubitus varus
      deformity of the elbow increases strain in the lateral ulnar collateral ligament,
      with a corresponding increase in ulnohumeral joint-opening consistent with the
      posterolateral rotatory instability of the elbow seen clinically.

PMID- 15466734
TI  - Osteoinductivity of commercially available demineralized bone matrix.
      Preparations in a spine fusion model.
AB  - BACKGROUND: Although autogenous bone is the most widely used graft material for
      spinal fusion, demineralized bone matrix preparations are available as
      alternatives or supplements to autograft. They are prepared by acid extraction of
      most of the mineralized component, with retention of the collagen and
      noncollagenous proteins, including growth factors. Differences in allograft
      processing methods among suppliers might yield products with different
      osteoinductive activities. The purpose of this study was to compare the efficacy
      of three different commercially available demineralized bone matrix products for
      inducing spinal fusion in an athymic rat model. METHODS: Sixty male athymic rats
      underwent spinal fusion and were divided into three groups of eighteen animals
      each. Group I received Grafton Putty; Group II, DBX Putty; and Group III,
      AlloMatrix Injectable Putty. A control group of six animals (Group IV) underwent
      decortication alone. Six animals from each of the three experimental groups were
      killed at each of three intervals (two, four, and eight weeks), and the six
      animals from the control group were killed at eight weeks. At each of the time
      points, radiographic and histologic analysis and manual testing of the explanted
      spines were performed. RESULTS: The spines in Group I demonstrated higher rates
      of radiographically evident fusion at eight weeks than did the spines in Group
      III or Group IV (p < 0.05). Manual testing of the spines at four weeks revealed
      variable fusion rates (five of six in Group I, two of six in Group II, and none
      of six in Group III). At eight weeks, all six spines in Group I, three of the six
      in Group II, and no spine in Group III or IV had fused. Histologic analysis of
      the spines in Groups I, II, and III demonstrated varying amounts of residual
      demineralized bone matrix and new bone formation. Group-I spines demonstrated the
      most new bone formation. CONCLUSIONS: This study demonstrated differences in the
      osteoinductive potentials of commercially available demineralized bone matrices
      in this animal model.

PMID- 15466735
TI  - Advancement and separation of apex hole eliminators with cementless Duraloc 100
      cups. A report of nineteen cases.
AB  - BACKGROUND: From 1992 to 1996, we performed 541 cementless total hip
      arthroplasties using a Duraloc 100 acetabular component with an apex hole
      eliminator that did not have a positive stop design. During routine follow-up
      radiographic evaluation, we noted several hips with advanced or separated hole
      eliminators. This study presents the clinical consequences of this occurrence and
      its relationship to polyethylene wear and osteolysis. METHODS: A total of 541
      hips (358 with a minimum duration of follow-up of five years) were evaluated
      clinically with use of the method of Merle D'Aubigne and Postel. Anteroposterior
      pelvic and iliac oblique radiographs were used to evaluate polyethylene wear,
      osteolysis, hole eliminator position, and component stability. RESULTS: Nineteen
      hips that had been followed for an average of eighty-nine months showed
      advancement or complete separation of the hole eliminator on radiographic
      evaluation. In most hips, advancement of the hole eliminator was visible on only
      the iliac oblique radiograph. In all but one hip with separation of the hole
      eliminator, complete plug separation was detectable on both the iliac oblique and
      anteroposterior pelvic radiographs. No association was found between polyethylene
      wear and either advancement or separation of the hole eliminator. No osteolysis
      was visible radiographically in the hips with hole eliminator advancement, but
      osteolysis was always visible in the hips that had complete separation of the
      hole eliminator. CONCLUSIONS: The hole eliminator has been redesigned since
      November 1995 to prevent possible advancement. However, patients with earlier
      designs should be followed carefully because advancement or separation can be
      expected in about 5% of the patients who have been followed for a minimum of five
      years. Despite this complication, which is seen radiographically, all patients
      were satisfied with the function of the hip. We do not recommend surgery solely
      to remove or replace the hole eliminator.

PMID- 15466736
TI  - The influence of an anterior-posterior gliding mobile bearing on range of motion
      after total knee arthroplasty. A prospective, randomized, double-blinded study.
AB  - BACKGROUND: Range of motion is a crucial measure of outcome after total knee
      arthroplasty. In order for maximum flexion to occur, the femur must progressively
      shift posteriorly on the tibia, a movement that is known as femoral rollback.
      Mobile bearings with free anterior-posterior translation could improve knee
      flexion by allowing such motion. The purpose of the present study was to
      determine the influence of an anterior-posterior gliding mobile bearing on the
      postoperative range of knee motion in patients with an intact posterior cruciate
      ligament. METHODS: We performed a prospective, randomized clinical trial of fifty
      consecutive total knee arthroplasties that were performed with use of the LCS
      Universal prosthesis. Participants were randomized to receive either a deep-dish
      rotating platform or a mobile bearing that allowed additional anterior-posterior
      translation, the latter of which requires an intact posterior cruciate ligament.
      The ranges of motion of the knees were assessed to detect a 15 degrees difference
      in the active non-weight-bearing range of motion with a power (1 - beta) of 20%
      and with the level of significance (alpha) set at 0.05. The translation of the
      mobile bearing was measured with use of a standardized ultrasound technique and
      was correlated with maximum knee flexion. The participants and the assessor were
      blinded throughout the study. RESULTS: At the time of the one-year follow-up
      evaluation, forty-eight knees were available for an intention-to-treat analysis.
      The mean active non-weight-bearing range of motion at one year was 113 degrees
      (95% confidence interval, 108 degrees to 118 degrees ) in the twenty-six knees
      that had received a rotating platform and 111 degrees (95% confidence interval,
      115 degrees to 125 degrees ) in the twenty-two knees that had received an
      anterior-posterior gliding bearing (p = 0.57). In the latter group, a continuous
      rollback occurred in two knees. There was no significant correlation between knee
      flexion and anterior-posterior translation (r(2) = 0.015). CONCLUSIONS: The use
      of a mobile bearing that allowed free anterior-posterior translation did not
      regularly restore femoral rollback and did not improve range of motion after
      total knee arthroplasty compared with the findings seen in association with the
      use of a rotating platform.

PMID- 15466737
TI  - Long-term results of total hip arthroplasty for femoral neck fracture nonunion.
AB  - BACKGROUND: Hip arthroplasty for the treatment of nonunion at the site of a
      femoral neck fracture has provided good short-term results. The purpose of the
      present study was to evaluate the long-term results and complications of total
      hip arthroplasty for the treatment of femoral neck nonunion. METHODS: The records
      of ninety-nine patients who had been managed with total hip arthroplasty with use
      of a cemented Charnley acetabular component and a cemented Charnley monoblock
      femoral component for the treatment of a femoral neck nonunion were
      retrospectively reviewed. The average age at the time of the arthroplasty was
      sixty-eight years. Eighty-four patients (85%) were followed until death,
      revision, or component removal or for at least two years (mean, 12.2 years)
      postoperatively. RESULTS: Twelve patients were treated with revision (eleven) or
      resection arthroplasty (one), eleven were lost to follow-up, and four died less
      than two years postoperatively. Of the remaining seventy-two unrevised hips that
      were followed for at least two years, sixty-nine (96%) had no or mild hip pain at
      the time of the last follow-up. The rate of component survival free of revision
      or removal for any reason was 93% at ten years and 76% at twenty years. The risk
      factors that were significantly associated with revision for aseptic loosening
      included an age of less than sixty-five years at the time of the arthroplasty (p
      = 0.045), a body-mass index of >/=30 (p < 0.01), and male gender (p = 0.02). The
      second most common complication after loosening was dislocation, which occurred
      in nine patients (9%). CONCLUSIONS: Total hip arthroplasty is an effective method
      for the treatment of nonunion of the femoral neck and provides satisfactory long
      term results. However, the rate of implant survival is poorer than that reported
      in most other studies of Charnley total hip arthroplasty in the general
      population.

PMID- 15466738
TI  - Dynamic contributions of the flexor-pronator mass to elbow valgus stability.
AB  - BACKGROUND: Previous studies have indicated that the demands placed on the medial
      ulnar collateral ligament of the elbow when it is subjected to valgus torque
      during throwing exceed its failure strength, which suggests the necessary dynamic
      contribution of muscle forces. We hypothesized that the flexor-pronator mass
      assists the medial ulnar collateral ligament in stabilizing the elbow against
      valgus torque. METHODS: Six cadaveric elbows were tested at 30 degrees and 90
      degrees of flexion with no other constraints to motion. A full medial ulnar
      collateral ligament tear was simulated in each elbow. Muscle forces were
      simulated on the basis of the centroids and physiological cross-sectional areas
      of individual muscles. The biceps, brachialis, and triceps were simulated during
      flexor carpi ulnaris, flexor digitorum superficialis, flexor digitorum
      superficialis and flexor carpi ulnaris, and pronator teres-loading conditions.
      Kinematic data were obtained at each flexion angle with use of a three
      dimensional digitizer. RESULTS: Release of the medial ulnar collateral ligament
      caused a significant increase in valgus instability of 5.9 degrees +/- 2.4
      degrees at 30 degrees of elbow flexion and of 4.8 degrees +/- 2.0 degrees at 90
      degrees of elbow flexion (p < 0.05). The differences in valgus angulation between
      each muscle-simulation condition and the medial ulnar collateral ligament-intact
      condition were significantly different from each other (p < 0.05), except for the
      difference between the flexor carpi ulnaris contraction condition and the flexor
      digitorum superficialis-flexor carpi ulnaris co-contraction condition. This co
      contraction provided the most correction of the valgus angle in comparison with
      the intact condition at both 30 degrees and 90 degrees of elbow flexion (1.1
      degrees +/- 1.8 degrees and 0.38 degrees +/- 2.3 degrees , respectively).
      Simulation of the flexor carpi ulnaris alone provided the greatest reduction of
      the valgus angle among all individual flexor-pronator mass muscles tested (p <
      0.05), whereas simulation of the pronator teres alone provided the least
      reduction of the valgus angle (p < 0.05). CONCLUSIONS: The flexor-pronator mass
      dynamically stabilizes the elbow against valgus torque. The flexor carpi ulnaris
      is the primary stabilizer, and the flexor digitorum superficialis is a secondary
      stabilizer. The pronator teres provides the least dynamic stability.

PMID- 15466739
TI  - Low-intensity transosseous ultrasound accelerates osteotomy healing in a sheep
      fracture model.
AB  - BACKGROUND: Low-intensity transcutaneous ultrasound can accelerate and augment
      the fracture-healing process. The aim of this study was to investigate the effect
      of transosseous application of low-intensity ultrasound on fracture-healing in an
      animal model. METHODS: A midshaft osteotomy of the left tibia was performed in
      forty sheep. An external fixator was used to stabilize the osteotomy site. A thin
      stainless-steel pin was inserted into the bone, 1.0 cm proximal to the osteotomy
      site. Ultrasound was transmitted through the free end of this pin, with a PZT-4D
      transducer. In twenty animals, the treated limb received a 200-microsec burst of
      1-MHz sine waves repeated at 1 kHz with an average intensity of 30 mW/cm(2) for
      twenty minutes daily. Twenty other animals underwent the same surgery but did not
      receive the ultrasound (controls). Animals were killed at seventy-five and 120
      days postoperatively. Radiographic evaluation was performed every fifteen days.
      Mechanical testing and quantitative computed tomography were performed after
      death. RESULTS: Fractures treated with ultrasound healed significantly more
      rapidly, as assessed radiographically, than did the controls (seventy-nine
      compared with 103 days, p = 0.027). On day 75, the mean cortical bone mineral
      density (and standard deviation) was 781 +/- 52 mg/mL in the treated limbs
      compared with 543 +/- 44 mg/mL in the control group (p = 0.014), and the average
      ultimate strength (as assessed with a lateral bending test) was 1928 +/- 167 N in
      the treated limbs compared with 1493 +/- 112 N in the control group (p = 0.012).
      No significant differences were noted on day 120. CONCLUSIONS: This study
      demonstrated that low-intensity transosseous ultrasound can significantly
      accelerate the fracture-healing process, increase the cortical bone mineral
      density, and improve lateral bending strength of the healing fracture in a sheep
      osteotomy model.

PMID- 15466740
TI  - Retained cement after unicondylar knee arthroplasty. A report of four cases.

PMID- 15466741
TI  - An unusual fracture-dislocation of the ankle. A case report.

PMID- 15466742
TI  - Humeral head osteonecrosis after anterior shoulder stabilization in an
      adolescent. A case report.

PMID- 15466743
TI  - Magnetic resonance imaging with gadolinium arthrography to assess acetabular
      cartilage delamination. A report of four cases.

PMID- 15466744
TI  - Transection of the plantar plate and the flexor digitorum longus tendon of the
      fourth toe as a complication of endoscopic treatment of interdigital neuroma. A
      case report.

PMID- 15466746
TI  - Osteomyelitis in long bones.
AB  - Osteomyelitis in long bones remains challenging and expensive to treat, despite
      advances in antibiotics and new operative techniques. Plain radiographs still
      provide the best screening for acute and chronic osteomyelitis. Other imaging
      techniques may be used to determine diagnosis and aid in treatment decisions. The
      decision to use oral or parenteral antibiotics should be based on results
      regarding microorganism sensitivity, patient compliance, infectious disease
      consultation, and the surgeon's experience. A suppressive antibiotic regimen
      should be directed by the results of cultures. Standard operative treatment is
      not feasible for all patients because of the functional impairment caused by the
      disease, the reconstructive operations, and the metabolic consequences of an
      aggressive therapy regimen. Operative treatment includes debridement,
      obliteration of dead space, restoration of blood supply, adequate soft-tissue
      coverage, stabilization, and reconstruction.

PMID- 15466745
TI  - Salvage of a prosthetic knee joint infected with resistant pneumococcus. A case
      report.

PMID- 15466747
TI  - It is what it is.

PMID- 15466748
TI  - The relationship between required medical school instruction in musculoskeletal
      medicine and application rates to orthopaedic surgery residency programs.
AB  - BACKGROUND: Orthopaedic residency programs lack gender and race diversity. This
      study examines the hypothesis that exposure to a required course in
      musculoskeletal medicine in medical school is associated with a higher rate of
      application to orthopaedic surgery residency programs by underrepresented groups.
      METHODS: All 122 medical schools in the United States were surveyed in 2001 to
      determine whether they required dedicated course work in musculoskeletal
      medicine, defined as a preclinical module or clinical clerkship in orthopaedic
      surgery, rheumatology, or physiatry. Data from the Electronic Residency
      Application Service were obtained for the class of 2002. From these two sources,
      the rate of applications from students to orthopaedic surgery residency programs
      was calculated as a function of exposure to a required course in musculoskeletal
      medicine. Subgroup analysis was further carried out for women and for African
      Americans, Latinos, and Native Americans. RESULTS: In 2002, there were 16,294
      graduates of American medical schools, of whom approximately 55% had mandatory
      instruction in musculoskeletal medicine. The rate of application to orthopaedic
      surgery residency programs was 5.7% among the students with required instruction
      compared with a rate of 5.1% for students without such required instruction. The
      rate of application for female students was 2.0% for those who had required
      courses and 1.1% for the female students who had not had the required courses.
      The rate of application for minority students in schools with required courses
      was 8.2% compared with a rate of 6.1% for those students without such exposure.
      CONCLUSIONS: Required instruction in musculoskeletal medicine was associated with
      a 12% higher rate of application to orthopaedic surgery residency programs among
      all students (5.7% of those who received required instruction compared with 5.1%
      of those who did not). The relative difference was more pronounced among women (a
      75% difference in the rate of application) and minorities (a 35% difference in
      the rate of application). This study suggests that required instruction in
      musculoskeletal medicine can help to promote diversity in orthopaedic surgery
      residency programs.

PMID- 15466749
TI  - Gifts from patients.

PMID- 15466750
TI  - What's new in hip arthroplasty.

PMID- 15466751
TI  - Uncemented STAR total ankle prostheses.
AB  - BACKGROUND: The feasibility of replacing the ankle joint has been a matter of
      speculation for a long time. In recent years, the designs of ankle prostheses
      have been improved, and three designs, all used without bone cement, currently
      dominate the market. However, documentation of the clinical results of the use of
      these prostheses is sparse. We reviewed the intermediate-term results of fifty
      one consecutive Scandinavian Total Ankle Replacements (STAR). METHODS: Between
      1993 and 1999, fifty-one consecutive ankles were replaced with an uncemented,
      hydroxyapatite-coated STAR total ankle prosthesis. Clinical examination for the
      present study was performed by one surgeon who had not taken part in the
      operations. Standardized radiographs were used. Complications and failures were
      recorded, and patient satisfaction and functional outcome scores were determined
      for all patients with an unrevised implant. RESULTS: Twelve ankles had to be
      revised. Seven were revised because of loosening of at least one of the
      components; two, because of fracture of the meniscus; and three, for other
      reasons. A component was exchanged in seven of the twelve revisions, whereas the
      ankle was successfully fused in the other five. An additional eight ankles had
      radiographic signs of loosening. The thirty-nine unrevised ankles (thirty-seven
      patients) were examined after thirty-six to ninety-seven months (median, fifty
      two months). The patient was satisfied with the result after thirty-one of the
      ankle replacements, somewhat satisfied after two, and not satisfied after six.
      The median Kofoed score increased from 39 points before the surgery to 70 points
      at the time of the follow-up examination. A median follow-up score of 74 points
      was recorded when the system described by Mazur et al. and the AOFAS (American
      Orthopaedic Foot and Ankle Society) system were used. The median range of motion
      was approximately the same preoperatively and postoperatively. The estimated five
      year survival rate, with revision for any reason as the end point, was 0.70. When
      radiographic loosening of either component was used as the end point, the
      estimated five-year radiographic survival rate was significantly better for the
      last thirty-one ankles treated in the series (p = 0.032). CONCLUSIONS: Total
      ankle replacement may be a realistic alternative to arthrodesis, provided that
      the components are correctly positioned and are of the correct size. However, the
      risks of loosening and failure are still higher than are such risks after total
      hip or total knee replacement.

PMID- 15466752
TI  - Reattachment of the ununited greater trochanter following total hip arthroplasty.
AB  - BACKGROUND: The purpose of this retrospective study was to analyze the utility of
      a trochanteric claw plate in the treatment of an ununited greater trochanter
      following total hip arthroplasty. METHODS: From 1986 through 1999, seventy-two
      consecutive procedures to reattach an ununited greater trochanter were performed
      in seventy-one patients. The average age at the time of the index arthroplasty
      was 66.2 years. The arthroplasty that resulted in the nonunion of the greater
      trochanter was primary in fifty-four hips, a first revision in sixteen hips, and
      a second and third revision in one hip each. The mean duration between the hip
      replacement and the treatment of the nonunion was 8.1 months. The greater
      trochanter was fixed with the trochanteric plate alone in forty-eight hips and
      with the plate in conjunction with vertical wires in the remaining twenty-four
      hips. The average duration of followup was 5.1 years. RESULTS: Osseous union
      occurred in fifty-one of the seventy-two hips. There was a persistent nonunion in
      twelve hips and fibrous consolidation in the remaining nine hips. The mean time
      to osseous consolidation was 3.7 +/- 2.1 months (range, two to twelve months).
      The mean Merle d'Aubigne hip score was 16.1 +/- 2.4 points at the time of the
      latest follow-up. A highly significant improvement in function was achieved only
      in the group with osseous consolidation (p < 0.0001). The highest rate of osseous
      union was achieved when vertical wires had been used in conjunction with the claw
      plate. Union occurred in twenty-one of the twenty-four hips in that group (p =
      0.025). CONCLUSIONS: Nonunion of the greater trochanter following total hip
      arthroplasty can be successfully treated with a trochanteric claw plate. The use
      of adjunctive vertical wires results in better osseous contact and union.

PMID- 15466753
TI  - Hallux rigidus.
AB  - BACKGROUND: There have been few long-term studies documenting the outcome of
      surgical treatment of hallux rigidus. The purposes of this report were to
      evaluate the long-term results of the operative treatment of hallux rigidus over
      a nineteen-year period in one surgeon's practice and to assess a clinical grading
      system for use in the treatment of hallux rigidus. METHODS: All patients in whom
      degenerative hallux rigidus had been treated with cheilectomy or
      metatarsophalangeal joint arthrodesis between 1981 and 1999 and who were alive at
      the time of this review were identified and invited to return for a follow-up
      evaluation. At this follow-up evaluation, the hallux rigidus was graded with a
      new five-grade clinical and radiographic system. Outcomes were assessed by
      comparison of preoperative and postoperative pain and AOFAS (American Orthopaedic
      Foot and Ankle Society) scores and ranges of motion. These outcomes were then
      correlated with the preoperative grade and the radiographic appearance at the
      time of follow-up. RESULTS: One hundred and ten of 114 patients with a diagnosis
      of hallux rigidus returned for the final evaluation. Eighty patients (ninety
      three feet) had undergone a cheilectomy, and thirty patients (thirty-four feet)
      had had an arthrodesis. The mean duration of follow-up was 9.6 years after the
      cheilectomies and 6.7 years after the arthrodeses. There was significant
      improvement in dorsiflexion and total motion following the cheilectomies (p =
      0.0001) and significant improvement in postoperative pain and AOFAS scores in
      both treatment groups (p = 0.0001). A good or excellent outcome based on patient
      self-assessment, the pain score, and the AOFAS score did not correlate with the
      radiographic appearance of the joint at the time of final follow-up. Dorsiflexion
      stress radiographs demonstrated correction of the elevation of the first ray to
      nearly zero. There was no association between hallux rigidus and hypermobility of
      the first ray, functional hallux limitus, or metatarsus primus elevatus.
      CONCLUSIONS: Ninety-seven percent (107) of the 110 patients had a good or
      excellent subjective result, and 92% (eighty-six) of the ninety-three cheilectomy
      procedures were successful in terms of pain relief and function. Cheilectomy was
      used with predictable success to treat Grade-1 and 2 and selected Grade-3 cases.
      Patients with Grade-4 hallux rigidus or Grade-3 hallux rigidus with <50% of the
      metatarsal head cartilage remaining at the time of surgery should be treated with
      arthrodesis.

PMID- 15466754
TI  - Unicompartmental knee arthroplasty in patients sixty years of age or younger.
AB  - BACKGROUND: Unicompartmental knee arthroplasty has been used to treat elderly,
      low-demand patients, but the literature is sparse regarding the use of this
      procedure for younger, active patients. The purpose of the present retrospective
      study was to evaluate the results of unicompartmental knee arthroplasty in
      younger, more active patients. METHODS: Forty-one patients underwent forty-six
      consecutive unicompartmental knee arthroplasties with use of the Miller-Galante
      system between 1988 and 1996. All of the patients were sixty years of age or
      younger and all were physically active. The Hospital for Special Surgery knee
      score and the University of California at Los Angeles activity assessment were
      used to rate the function and to determine the activity level of each patient,
      respectively. Serial radiographs were used to evaluate the status of prosthetic
      fixation, femorotibial alignment, and the progression of arthrosis in the
      unreplaced compartment. Long-term survivorship was calculated with use of Kaplan
      Meier analysis. RESULTS: The mean duration of follow-up was eleven years. Of the
      forty-five knees that were available for follow-up, three had been revised. The
      Hospital for Special Surgery score was excellent for thirty-nine (93%) of the
      remaining forty-two knees and good for three. The University of California at Los
      Angeles activity assessment score was 6.6 +/- 1.4 for the knees in which the
      original prosthesis had been retained and 7.3 +/- 1.5 for those in which it had
      been revised. Two asymptomatic patients had revision of a modular tibial
      component because of substantial radiographic evidence of polyethylene wear; one
      of these patients had exchange of the polyethylene insert and the tibial tray,
      and the other had exchange of the polyethylene insert only. A third patient
      underwent revision total knee arthroplasty because of continuing knee pain and a
      progressive tibial radiolucent line that was >2 mm in width. The average
      postoperative femorotibial alignment was 5 degrees of valgus. Nine knees had
      progression of arthritis in the unresurfaced compartment; none of these knees
      were revised, and none of the patients had deterioration in the Hospital for
      Special Surgery score. Kaplan-Meier analysis demonstrated an eleven-year
      survivorship of 92%. CONCLUSIONS: At an average duration of follow-up of eleven
      years, unicompartmental knee arthroplasty was associated with pain relief and
      excellent function in a cohort of patients who had been sixty years of age or
      younger and active at the time of surgery.

PMID- 15466755
TI  - Severely impacted valgus proximal humeral fractures.
AB  - BACKGROUND: The functional results associated with nonoperative treatment of
      severely impacted valgus fractures of the proximal part of the humerus are poor,
      and these injuries are difficult to treat with minimally invasive percutaneous
      fixation techniques. The aim of this study was to review the functional and
      radiographic results and complications of a new operative technique in a series
      of twenty-five patients. METHODS: Over a two-year period, we treated twenty-nine
      patients with a severely impacted valgus fracture of the proximal part of the
      humerus. Three patients were lost to follow-up and one died, leaving twenty-five
      patients who were available for the study. In all of the fractures, the head
      shaft angle had been tilted into > or = 160 degrees of valgus and the greater
      tuberosity was displaced by >1 cm. All patients were treated with open reduction
      of the fracture, and the space created behind the humeral head was filled with
      Norian Skeletal Repair System (SRS) bone substitute. The fractures were
      stabilized with either screws or buttress plate fixation. Associated rotator cuff
      tears were repaired. All patients underwent functional outcome assessment with
      use of the Constant, DASH (Disabilities of the Arm, Shoulder and Hand), and SF-36
      (Short Form-36) scores at one year, and twelve patients were followed for two
      years. RESULTS: All fractures united within the first year, all reductions were
      maintained, and no patient had signs of osteonecrosis of the humeral head on the
      latest follow-up radiographs. At one year, the median Constant score was 80
      points and the median DASH score was 22 points. The functional results continued
      to be satisfactory in the twelve patients who were followed for two years. The
      results in our series were better than those achieved in studies of nonoperative
      treatment of similar fracture configurations. There were six clinically relevant
      complications, although none required a reoperation and all six patients had a
      satisfactory short-term functional outcome. CONCLUSIONS: Internal fixation of
      severely impacted valgus fractures of the proximal part of the humerus,
      supplemented by Norian SRS bone substitute to fill the proximal humeral
      metaphyseal defect, produces good early functional and radiographic outcomes.
      Additional follow-up will be required to assess whether these initially
      satisfactory outcomes are maintained over the longer term.

PMID- 15466756
TI  - Correction of sagittal plane spinal deformities with unit rod instrumentation in
      children with cerebral palsy.
AB  - BACKGROUND: To our knowledge, there have been no previous studies addressing the
      indications for and the results of treatment of patients with cerebral palsy and
      concomitant kyphosis or lordosis without scoliosis. The purpose of the present
      study was to identify the indications for and the results of treatment of
      patients with cerebral palsy who have a spinal curve deformity solely in the
      sagittal plane. METHODS: We conducted a retrospective review of the data on all
      patients with cerebral palsy who had a sagittal plane spinal deformity but no
      coronal plane deformity, had undergone posterior spinal fusion with unit rod
      instrumentation at our institution, and had been followed for at least two years.
      Medical records and radiographs were reviewed for symptoms, type and magnitude of
      deformity, age at surgery, duration of surgery, nutritional status,
      complications, and concomitant medical problems. RESULTS: Twenty-four patients-
      ten boys and fourteen girls--were identified. Eight patients had a hyperlordotic
      deformity, fourteen had a hyperkyphotic deformity, and two exhibited both.
      Surgical indications included severe seating problems that could not be rectified
      with wheelchair modifications (eighteen patients), severe back pain (four
      patients), superior mesenteric artery syndrome that was refractory to
      conservative treatment (two patients), and a hyperlordotic deformity with a loss
      of bowel and bladder control (one patient). It was found that specific technical
      concerns had to be addressed when the unit rod instrumentation was used. The mean
      preoperative hyperkyphotic curve of 93.8 degrees was corrected to a mean of 35.8
      degrees postoperatively and was a mean of 34.8 degrees at the last visit. The
      mean preoperative hyperlordotic curve of 91.8 degrees was corrected to a mean of
      43.6 degrees postoperatively and was a mean of 48.6 degrees at the last visit.
      All patients with seating problems and back pain had improvement or resolution of
      the problem after the surgery. The superior mesenteric artery syndromes, losses
      of bowel and bladder function, and malnutrition all resolved completely after the
      surgery. CONCLUSIONS: Patients with cerebral palsy and a severe sagittal plane
      deformity (> or = 70 degrees ) can be treated successfully with posterior spinal
      fusion with use of unit rod instrumentation. Indications for treatment include
      loss of sitting ability or balance, back pain, loss of bowel or bladder function,
      and superior mesenteric artery syndrome that is unresponsive to medical
      management.

PMID- 15466757
TI  - Results of the musculofascial lengthening technique for submuscular transposition
      of the ulnar nerve at the elbow.
AB  - BACKGROUND: In the absence of a randomized, prospective study comparing different
      surgical approaches for decompression of the ulnar nerve at the elbow, the choice
      of an approach relies on the individual surgeon's training and experience. The
      present report describes the results of a prospective, long-term evaluation of
      the musculofascial lengthening technique in a large series of patients. In these
      patients, the degree of ulnar nerve compression was staged with use of a
      numerical grading system that included measures of both motor and sensory
      function. METHODS: From 1985 through 1991, 121 consecutive patients (161 ex
      tremities) in whom the ulnar nerve was entrapped at the elbow were treated with
      surgical decompression with use of a musculofascial lengthening technique. In
      addition to the patient history and physical examination, measurements of sensory
      and motor function were obtained prospectively to permit staging of the severity
      of the compression by means of a grading scale. The preoperative and
      postoperative scores on this scale were evaluated. The mean duration of follow-up
      after surgery was 45.6 months. RESULTS: On the basis of traditional criteria, 105
      limbs (65%) had an excellent result; thirty-seven (23%), a good result; six (4%),
      afair result; twelve (7.5%), a failure; and one (0.5%), a recurrence. There was
      significant improvement in ulnar nerve function in terms of both the sensory (p <
      0.001) and motor (p < 0.001) components of the grading scale. Comparisons of
      clinical subgroups revealed significant improvement in patients with diabetes,
      those with a Workers' Compensation claim, and those who had a severe degree of
      compression rather than a mild degree of compression. CONCLUSIONS: Surgical
      decompression of ulnar nerve entrapment at the elbow by means of a musculofascial
      lengthening technique was associated with an 88% rate of good to excellent
      results. The results of the present study demonstrate the feasibility of
      performing a statistical analysis of surgical results by using a numerical
      grading system to stage the degree of nerve compression. This method may be used
      to study different surgical techniques for the treatment of this common nerve
      compression syndrome.

PMID- 15466758
TI  - Surgical treatment of talar body fractures.
AB  - BACKGROUND: Fractures of the body of the talus are uncommon and poorly described.
      The purposes of the present study were to characterize these fractures, to
      describe one treatment approach, and to evaluate the clinical, radiographic, and
      functional outcomes of operative treatment. METHODS: Fifty-six patients with
      fifty-seven talar body fractures who had been treated operatively during a sixty
      seven-month period at a level-1 trauma center were identified with use of a
      database. Twenty-three patients had a concomitant talar neck fracture. Eleven of
      the fifty-seven fractures were open. All patients underwent open reduction and
      internal fixation. Complications, secondary procedures, and the ability to return
      to work were evaluated at a minimum of one year. The radiographic presence of
      osteonecrosis and posttraumatic arthritis was ascertained. Foot Function Index
      and Musculoskeletal Function Assessment questionnaires were completed. RESULTS:
      Thirty-eight patients were evaluated after an average duration of follow-up of
      thirty-three months. Early complications occurred in eight patients. Ten of the
      twenty-six patients who had a complete set of radiographs had development of
      osteonecrosis of the talar body. Five of these ten patients experienced collapse
      of the talar dome at a mean of 10.2 months after surgery. All patients with a
      history of both an open fracture and osteonecrosis experienced collapse.
      Seventeen of twenty-six patients had posttraumatic arthritis of the tibiotalar
      joint, and nine of twenty-six had posttraumatic arthritis of the subtalar joint.
      Fractures of both the talar body and neck led to development of advanced
      arthritis more frequently than did fractures of the talar body only (p = 0.04).
      All patients with open fractures had end-stage posttraumatic arthritis (p =
      0.053). Twenty-three (88%) of twenty-six patients had radiographic evidence of
      osteonecrosis and/or posttraumatic arthritis. Worse outcomes were noted in
      association with comminuted and open fractures. Osteonecrosis and posttraumatic
      arthritis adversely affected outcome scores. CONCLUSIONS: Open reduction and
      internal fixation of talar body fractures may restore congruity of the adjacent
      joints. However, early complications are not infrequent, and most patients have
      development of radiographic evidence of osteonecrosis and/or posttraumatic
      arthritis. Associated talar neck fractures and open fractures more commonly
      result in osteonecrosis or advanced arthritis. Worse functional outcomes are seen
      in association with advanced posttraumatic arthritis and osteonecrosis that
      progresses to collapse. It is important to counsel patients regarding these
      devastating injuries and their poor prognosis and potential complications.

PMID- 15466759
TI  - Mesh expansion release of the lateral patellar retinaculum during total knee
      arthroplasty.
AB  - BACKGROUND: Release of the lateral patellar retinaculum can be used to treat
      patellofemoral instability and to balance the extensor mechanism during knee
      replacement operations. However, conventional lateral release disrupts the
      integrity of the lateral knee capsule, may damage the blood supply to the
      patella, and is associated with several other potential complications. Mesh
      expansion release of the lateral patellar retinaculum was developed to achieve
      the goal of lateral release and to reduce the potential for postoperative
      morbidity. METHODS: Thirteen consecutive knees in eleven patients were treated
      with mesh expansion lateral release during a total knee arthroplastyand were
      evaluated after a minimum duration of follow-up of two years. The mesh release
      technique consisted of multiple, longitudinal, parallel 5 to 10-mm stab incisions
      to mesh and expand the lateral patellar retinaculum and thereby medialize the
      patella in the trochlear groove of the femoral implant. RESULTS: Mesh expansion
      lateral release balanced the extensor mechanism in each knee, maintained the
      mechanical integrity of the lateral capsule, and avoided disruption of the
      lateral genicular blood supply to the patella. After a minimum duration of follow
      up of two years, no complications had been noted in association with mesh
      expansion lateral release. CONCLUSIONS: Mesh expansion release of the lateral
      patellar retinaculum effectively balanced the patellofemoral joint during total
      knee arthroplasty, maintained the integrity of the lateral capsule, and preserved
      the lateral genicular blood supply.

PMID- 15466760
TI  - Transepiphyseal replacement of the anterior cruciate ligament using quadruple
      hamstring grafts in skeletally immature patients.
AB  - BACKGROUND: Fear of iatrogenic growth disturbance has prevented the routine use,
      in children, of anatomic methods of anterior cruciate ligament replacement that
      have proven successful in adults. To minimize the risk of growth disturbance,
      extra-articular or modified physeal sparing procedures have been performed to
      stabilize the knee, but these procedures do not provide isometry. This study was
      performed to evaluate the results of a transepiphyseal replacement of the
      anterior cruciate ligament in skeletally immature athletes. METHODS: From 1993 to
      1999, twelve patients with a mean age (and standard deviation) of 13.3 +/- 1.4
      years underwent replacement of the anterior cruciate ligament with a quadruple
      hamstring tendon graft performed with an arthroscopic technique and
      intraoperative fluoroscopic imaging for precise tunnel placement. The femoral and
      tibial tunnels went through the epiphyses but avoided the physes. Eight of the
      twelve patients also had a meniscal repair. All patients returned for follow-up,
      at a mean of 4.1 +/- 1.9 years (range, two to 8.2 years) after surgery. RESULTS:
      The mean amount of growth from the time of surgery to the time of follow-up was
      16.5 +/- 10.0 cm (range, 8 to 38 cm). The difference between the lengths of the
      lower limbs, as measured on orthoradiographs, was not clinically relevant. The
      mean score on the International Knee Documentation Committee (IKDC) subjective
      knee form was 96.5 +/- 4.4 points (range, 86 to 100 points). Ligament laxity
      testing with a KT-1000 arthrometer revealed a mean side-to-side difference of 1.5
      +/- 1.1 mm. The rating according to the criteria of the objective 2001 IKDC knee
      form was normal for seven patients and nearly normal for five. CONCLUSIONS:
      Transepiphyseal replacement of the anterior cruciate ligament, a technically
      demanding procedure with a small margin of error, should be attempted only by
      accomplished knee surgeons. The preliminary results in this small series,
      however, demonstrate that this surgical technique can be performed in
      prepubescent patients with efficacy and relative safety.

PMID- 15466761
TI  - Summaries for patients. Prednisone plus methotrexate for polymyalgia rheumatica.

PMID- 15466762
TI  - Summaries for patients. The cost-effectiveness of screening for Chlamydia in
      women 15 to 29 years of age.

PMID- 15466763
TI  - Summaries for patients. Dietary fat and risk for gallstone disease in men.

PMID- 15466764
TI  - Summaries for patients. A comparison of different programs to improve preventive
      care for cardiovascular conditions.

PMID- 15466765
TI  - Chronic pancreatitis associated with adult-onset type II citrullinemia: clinical
      and pathologic findings.

PMID- 15466766
TI  - Prednisone plus methotrexate for polymyalgia rheumatica: a randomized, double
      blind, placebo-controlled trial.
AB  - BACKGROUND: Steroids are the standard treatment for polymyalgia rheumatica. The
      efficacy of the candidate drug methotrexate has not yet been demonstrated in
      controlled studies. OBJECTIVE: To compare the efficacy and safety of prednisone
      plus methotrexate and prednisone alone in patients with polymyalgia rheumatica.
      DESIGN: Multicenter randomized, double-blind, placebo-controlled trial. SETTING:
      5 Italian rheumatology clinics. PATIENTS: 72 patients with newly diagnosed
      polymyalgia rheumatica. MEASUREMENTS: The proportion of patients no longer taking
      prednisone, the number of flare-ups, and the cumulative prednisone dose after 76
      weeks. INTERVENTION: Prednisone dosage (25 mg/d) was tapered to 0 mg/d within 24
      weeks and was adjusted if flare-ups occurred. Oral methotrexate (10 mg) or
      placebo, with folinic acid supplementation (7.5 mg), was given weekly for 48
      weeks. RESULTS: Twenty-eight of 32 patients in the methotrexate group and 16 of
      30 patients in the placebo group were no longer taking prednisone at 76 weeks (P
      = 0.003). The risk difference was 34 percentage points (95% CI, 11 to 53
      percentage points). Similar results were obtained after adjustment for C-reactive
      protein level and duration of symptoms in a multivariate model. Fifteen of 32
      patients in the methotrexate group and 22 of 30 patients in the placebo group had
      at least 1 flare-up by the end of follow-up (P = 0.04). The median prednisone
      dose was 2.1 g in the methotrexate group and 2.97 g in the placebo group (P =
      0.03). The rate and severity of adverse events were similar. LIMITATIONS: Follow
      up was short, and a high dose of folinic acid and a relatively high starting
      dosage of prednisone were used. Ten of 72 patients (14%) discontinued treatment
      or were lost to follow-up. CONCLUSIONS: Prednisone plus methotrexate is
      associated with shorter prednisone treatment and steroid sparing. It may be
      useful in patients at high risk for steroid-related toxicity.

PMID- 15466767
TI  - Screening for Chlamydia trachomatis in women 15 to 29 years of age: a cost
      effectiveness analysis.
AB  - BACKGROUND: Clinical guidelines have traditionally advised annual Chlamydia
      trachomatis screening for women younger than 25 years of age. OBJECTIVE: To
      assess the cost-effectiveness of recently proposed strategies for chlamydia
      screening. DESIGN: State transition simulation model; cost-effectiveness
      analysis. DATA SOURCES: Published literature. TARGET POPULATION: Sexually active
      U.S. women 15 to 29 years of age. TIME HORIZON: Lifetime. PERSPECTIVE: Modified
      societal. INTERVENTIONS: Four strategies targeted to 3 specific age groups (15 to
      19 years, 15 to 24 years, and 15 to 29 years): 1) no screening, 2) annual
      screening for all women, 3) annual screening followed by 1 repeated test within 3
      to 6 months after a positive test result, and 4) annual screening followed by
      selective semiannual screening for women with a history of infection. OUTCOME
      MEASURES: Clinical events (for example, pelvic inflammatory disease, chronic
      pelvic pain, ectopic pregnancy, and infertility), lifetime costs, quality
      adjusted life expectancy, and incremental cost-effectiveness ratios. RESULTS OF
      BASE-CASE ANALYSIS: Annual screening in women 15 to 29 years of age followed by
      semiannual screening for those with a history of infection was the most effective
      and cost-effective strategy. It consistently had an incremental cost
      effectiveness ratio less than 25,000 dollars per quality-adjusted life-year
      (QALY) compared with the next most effective strategy. When the indirect
      transmission effects of a 10-year screening program on the probability of
      infection in uninfected women (that is, per-susceptible rate of infection) were
      considered, all strategies became more cost-effective. RESULTS OF SENSITIVITY
      ANALYSIS: Results were sensitive to the annual incidence of chlamydia,
      probability of persistent infection, screening test costs, and costs of treating
      long-term complications. Each variable was associated with threshold values
      beyond which screening became cost-saving. In probabilistic analysis, annual
      screening in women 15 to 29 years of age followed by semiannual screening for
      those with a history of infection had an incremental cost-effectiveness ratio
      less than 50,000 dollars per QALY in 99% of simulations. LIMITATIONS: Uncertainty
      about the natural history of chlamydial infection and consideration of only the
      indirect transmission effects of C. trachomatis screening. CONCLUSIONS: Annual C.
      trachomatis screening for all women 15 to 29 years of age and selective targeting
      of those with a history of infection for semiannual screening is very cost
      effective compared with other well-accepted clinical interventions.

PMID- 15466768
TI  - The effect of long-term intake of cis unsaturated fats on the risk for gallstone
      disease in men: a prospective cohort study.
AB  - BACKGROUND: Monounsaturated and polyunsaturated fats act as inhibitors of
      cholesterol cholelithiasis in animal experiments. OBJECTIVE: To examine the
      association between long-term intake of cis unsaturated fats and the incidence of
      gallstone disease in humans. DESIGN: Prospective population-based cohort study.
      SETTING: The Health Professional Follow-up Study. PARTICIPANTS: 45,756 men, age
      40 to 75 years in 1986, who were free of gallstone disease. MEASUREMENTS:
      Consumption of cis unsaturated fats was assessed starting in 1986 as part of the
      131-item semi-quantitative food-frequency questionnaires. Questionnaires were
      mailed to participants every 2 years. The main outcome measure was self-reported
      newly diagnosed symptomatic gallstone disease. RESULTS: During 14 years of follow
      up, 2323 new cases of gallstone disease were documented. After adjustment for age
      and other potential risk factors, the relative risk for gallstone disease among
      men in the highest quintile of dietary intake of cis unsaturated fats compared
      with men in the lowest quintile was 0.82 (95% CI, 0.69 to 0.96; P for trend =
      0.006). The relative risk among men in the highest quintile of polyunsaturated
      fat consumption compared with men in the lowest quintile was 0.84 (CI, 0.73 to
      0.96; P for trend = 0.01), and the relative risk among men in the highest
      quintile of monounsaturated fat consumption compared with men in the lowest
      quintile was 0.83 (CI, 0.70 to 1.00; P for trend = 0.01). LIMITATIONS: Outcomes
      were restricted to men with cholecystectomy or diagnostically confirmed but
      unremoved symptomatic gallstones. CONCLUSIONS: A high intake of polyunsaturated
      and monounsaturated fats in the context of an energy-balanced diet is associated
      with a reduced risk for gallstone disease in men. For definitions of terms used
      in the text, see Glossary.

PMID- 15466769
TI  - A multimethod quality improvement intervention to improve preventive
      cardiovascular care: a cluster randomized trial.
AB  - BACKGROUND: Research is needed to validate effective and practical strategies for
      improving the provision of evidence-based medicine in primary care. OBJECTIVE: To
      determine whether a multimethod quality improvement intervention was more
      effective than a less intensive intervention for improving adherence to 21
      quality indicators for primary and secondary prevention of cardiovascular disease
      and stroke. DESIGN: 2-year randomized, controlled clinical trial with the
      practice as the unit of randomization. SETTING: 20 community-based family or
      general internal medicine practices in 14 states. All used the same electronic
      medical record. PARTICIPANTS: 44 physicians, 17 midlevel providers, and
      approximately 200 staff members; data from the electronic medical records of
      87,291 patients. INTERVENTIONS: All practices received copies of practice
      guidelines and quarterly performance reports. Intervention practices also hosted
      quarterly site visits to help them adopt quality improvement approaches and
      participated in 2 network meetings to share "best practice" approaches.
      MEASUREMENTS: The percentage of indicators at or above predefined targets and the
      percentage of patients who had achieved each clinical indicator. RESULTS:
      Intervention practices improved 22.4 percentage points (from 11.3% to 33.7%) in
      the percentage of indicators at or above the target; control practices improved
      16.4 percentage points (from 6.3% to 22.7%). The 6.0-percentage point absolute
      difference between the intervention and control group was not statistically
      significant (P > 0.2). Patients in intervention practices had greater
      improvements than those in control practices for diagnoses of hypertension
      (improvement difference, 15.7 percentage points [95% CI, 5.2 to 26.3 percentage
      points]) and blood pressure control in patients with hypertension (improvement
      difference, 8.0 percentage points [CI, 0.0 to 16.0 percentage points]).
      LIMITATIONS: The study involved a small number of practices and lacked a pure
      control group. CONCLUSIONS: Primary care practices that use electronic medical
      records and receive regular performance reports can improve their adherence to
      clinical practice guidelines for cardiovascular disease and stroke prevention.

PMID- 15466770
TI  - Lost in transition: challenges and opportunities for improving the quality of
      transitional care.
AB  - Transitional care has been defined as a set of actions designed to ensure the
      coordination and continuity of health care as patients transfer between different
      locations or different levels of care in the same location. Transitional care,
      which primarily concerns the relatively brief time interval that begins with
      preparing a patient to leave one setting and concludes when the patient is
      received in the next setting, poses challenges that distinguish it from other
      types of care. Many transitions are unplanned, result from unanticipated medical
      problems, occur in "real time" during nights and on weekends, involve clinicians
      who may not have an ongoing relationship with the patient, and happen so quickly
      that formal and informal support mechanisms cannot respond in a timely manner.
      This article describes the challenges involved in and potential solutions for
      improving the quality of transitional care.

PMID- 15466771
TI  - Systematic review: computed tomography and ultrasonography to detect acute
      appendicitis in adults and adolescents.
AB  - BACKGROUND: Although clinicians commonly use computed tomography or
      ultrasonography to diagnose acute appendicitis, the accuracy of these imaging
      tests remains unclear. PURPOSE: To review the diagnostic accuracy of computed
      tomography and ultrasonography in adults and adolescents with suspected acute
      appendicitis. DATA SOURCES: The authors used MEDLINE, EMBASE, bibliographies,
      review articles, textbooks, and expert opinion to retrieve English- and non
      English-language articles published from 1966 to December 2003. STUDY SELECTION:
      The authors included prospective studies evaluating computed tomography or
      ultrasonography followed by surgical confirmation or clinical follow-up in
      patients at least 14 years of age with suspected appendicitis. DATA EXTRACTION:
      One assessor (for non-English-language studies) or 2 assessors (for English
      language studies) independently reviewed each article to abstract relevant study
      characteristics and results. DATA SYNTHESIS: Twelve computed tomography studies
      and 14 ultrasonography studies met inclusion criteria. Computed tomography had an
      overall sensitivity of 0.94 (95% CI, 0.91 to 0.95), a specificity of 0.95 (CI,
      0.93 to 0.96), a positive likelihood ratio of 13.3 (CI, 9.9 to 17.9), and a
      negative likelihood ratio of 0.09 (CI, 0.07 to 0.12). Ultrasonography had an
      overall sensitivity of 0.86 (CI, 0.83 to 0.88), a specificity of 0.81 (CI, 0.78
      to 0.84), a positive likelihood ratio of 5.8 (CI, 3.5 to 9.5), and a negative
      likelihood ratio of 0.19 (CI, 0.13 to 0.27). Verification bias and inappropriate
      blinding of reference standards were noted in all of the included studies.
      LIMITATIONS: The summary assessment of the diagnostic accuracy for both tests was
      limited by the small number of studies, heterogeneity among study samples, and
      poor methodologic quality in the original studies. CONCLUSIONS: Computed
      tomography is probably more accurate than ultrasonography for diagnosing
      appendicitis in adults and adolescents. Prospective studies that apply gold
      standard diagnostic testing to all study participants would more reliably
      estimate the true diagnostic accuracy of these tests.

PMID- 15466772
TI  - Malaria-related deaths among U.S. travelers, 1963-2001.
AB  - Nearly 1500 malaria cases occur each year in the United States; approximately 60%
      are among U.S. travelers. Despite the availability of sophisticated medical care,
      malaria-related deaths continue to occur. The authors reviewed all 185 fatal
      cases between 1963 and 2001 that were reported to the National Malaria
      Surveillance System: 123 (66.5%) occurred among U.S. travelers, and of these, 114
      (92.7%) were attributed to Plasmodium falciparum. Failure to take or adhere to
      recommended chemoprophylaxis, to promptly seek medical care for post-travel
      illness, and to promptly diagnose and treat suspected malaria all contributed to
      fatal outcomes. Health care providers need to take a travel history, obtain a
      blood film for suspected malaria, and use the 24-hour malaria management advice
      available through the Centers for Disease Control and Prevention (CDC) Malaria
      Hotline (770-488-7788) or the CDC Malaria Web site (http://www.cdc.gov/Malaria).
      Hospitals must maintain intravenous quinidine gluconate on formulary because it
      is the only drug available to treat severe malaria in the United States.

PMID- 15466773
TI  - Insuring the uninsured: will the 2004 election provide an answer?

PMID- 15466774
TI  - Primary care management of chronic stable angina and asymptomatic suspected or
      known coronary artery disease: a clinical practice guideline from the American
      College of Physicians.
AB  - In 1999, the American College of Physicians (ACP), then the American College of
      Physicians-American Society of Internal Medicine, and the American College of
      Cardiology/American Heart Association (ACC/AHA) developed joint guidelines on the
      management of patients with chronic stable angina. The ACC/AHA then published an
      updated guideline in 2002, which ACP recognized as a scientifically valid review
      of the evidence and background paper. This ACP guideline summarizes the
      recommendations of the 2002 ACC/AHA updated guideline and underscores the
      recommendations most likely to be important to physicians seeing patients in the
      primary care setting. This guideline is the second of 2 that provide guidance on
      the management of patients with chronic stable angina. This document covers
      treatment and follow-up of symptomatic patients who have not had an acute
      myocardial infarction or revascularization procedure in the previous 6 months.
      Sections addressing asymptomatic patients are also included. Asymptomatic refers
      to patients with known or suspected coronary disease based on a history or
      electrocardiographic evidence of previous myocardial infarction, coronary
      angiography, or abnormal results on noninvasive tests. A previous guideline
      covered diagnosis and risk stratification for symptomatic patients who have not
      had an acute myocardial infarction or revascularization procedure in the previous
      6 months and asymptomatic patients with known or suspected coronary disease based
      on a history or electrocardiographic evidence of previous myocardial infarction,
      coronary angiography, or abnormal results on noninvasive tests.

PMID- 15466775
TI  - Methotrexate in polymyalgia rheumatica: kernel of truth or curse of Tantalus?

PMID- 15466776
TI  - Chlamydia screening: expanding the scope.

PMID- 15466777
TI  - Northwoods elegy.

PMID- 15466778
TI  - Screening for hepatitis C virus infection in adults.

PMID- 15466779
TI  - Survival versus prognosis in Alzheimer disease.

PMID- 15466781
TI  - Selective decontamination of the digestive tract and prevention of ventilator
      associated pneumonia.

PMID- 15466782
TI  - Variability in diagnostic probability estimates.

PMID- 15466783
TI  - The domain of general internal medicine: a perspective from trainees.

PMID- 15466784
TI  - Blockade of platelet-derived growth factor receptor-beta by CDP860, a humanized,
      PEGylated di-Fab', leads to fluid accumulation and is associated with increased
      tumor vascularized volume.
AB  - PURPOSE: CDP860 is an engineered Fab' fragment-polyethylene glycol conjugate,
      which binds to and blocks the activity of the beta-subunit of the platelet
      derived growth factor receptor (PDGFR-beta). Studies in animals have suggested
      that PDGFR-beta inhibition reduces tumor interstitial fluid pressure, and thus
      increases the uptake of concomitantly administered drugs. The purpose of this
      study was to determine whether changes in tumor vascular parameters could be
      detected in humans, and to assess whether CDP860 would be likely to increase the
      uptake of a concurrently administered small molecule in future studies. PATIENTS
      AND METHODS: Patients with advanced ovarian or colorectal cancer and good
      performance status received intravenous infusions of CDP860 on days 0 and 28.
      Patients had serial dynamic contrast-enhanced magnetic resonance imaging studies
      to measure changes in tumor vascular parameters. RESULTS: Three of eight patients
      developed significant ascites, and seven of eight showed evidence of fluid
      retention. In some patients, the ratio of vascular volume to total tumor volume
      increased significantly (P < .001) within 24 hours following CDP860
      administration, an effect suggestive of recruitment of previously non-functioning
      vessels. CONCLUSION: These observations suggest that inhibition of PDGFR-beta
      might improve delivery of a concurrently administered therapy. However, in cancer
      patients, further exploration of the dosing regimen of CDP860 is required to
      dissociate adverse effects from beneficial effects. The findings challenge the
      view that inhibition of PDGF alone is beneficial, and confirm that effects of
      PDGFR kinase inhibition mediate, to some extent, the fluid retention observed in
      patients treated with mixed tyrosine kinase inhibitors.

PMID- 15466785
TI  - Quality of life in ovarian cancer patients: comparison of paclitaxel plus
      cisplatin, with cyclophosphamide plus cisplatin in a randomized study.
AB  - PURPOSE: Formal quality-of-life (QOL) assessments may contribute important
      information on patient symptoms. Despite many trials of systemic chemotherapy in
      ovarian cancer, reports of its effect on QOL are few. PATIENTS AND METHODS: QOL
      was assessed in an Intergroup randomized trial comparing paclitaxel plus
      cisplatin to cyclophosphamide plus cisplatin in women with advanced ovarian
      cancer. One hundred fifty-two eligible patients accrued in Canada completed the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire C30 and a trial-specific checklist at baseline (after surgical
      debulking) and at regular intervals during and after chemotherapy. Mean change
      scores over time in the two arms were calculated. RESULTS: Compliance with QOL
      questionnaire completion was excellent (81% to 93%). In general, deterioration
      was seen in the QOL domains immediately after chemotherapy (day 8 of cycle 1),
      followed by clinically meaningful improvements compared with baseline (change
      scores > or = 10) in both arms during the treatment period in a number of domains
      and items, including global QOL, emotional function, social function, fatigue,
      pain, sleep, constipation, appetite, abdominal swelling, and abdominal cramps.
      Improvements in global QOL persisted for the duration of follow-up. More
      neurosensory effects and myalgia were documented in the paclitaxel arm; however,
      this did not adversely affect global or other domains of QOL and improved once
      chemotherapy was completed. CONCLUSION: Improvement from baseline in QOL measures
      was seen in both treatment arms. The greater neurologic and muscle toxicity of
      paclitaxel did not adversely influence QOL. QOL data can contribute useful
      information on the experience of symptoms and their time course, which may assist
      patients and physicians in their discussion about the anticipated effects of
      therapy.

PMID- 15466786
TI  - Criteria for facilities and personnel for the administration of parenteral
      systemic antineoplastic therapy. Adopted on March 3, 2004 by the American Society
      of Clinical Oncology.
AB  - The following American Society of Clinical Oncology (ASCO) position statement
      represents an update to policy first adopted by the Board in 1997 (J Clin Oncol
      15:3416-3417, 1997). The primary change to the statement is the addition of
      language to section 7, Standards for Antineoplastic Therapy, describing
      safeguards for preparing and administering chemotherapy drugs. As third-party
      payors consider and follow through with the establishment of new models for
      chemotherapy drug procurement, distribution, and delivery, ASCO provides guidance
      to oncologists to help them ensure the safety and integrity of the drugs they
      administer. Additionally, section 5, Office Operations, also suggests that
      oncologists consider measures protecting them from liability associated with
      drugs obtained from or prepared by outside entities.

PMID- 15466787
TI  - Nitinol stents in hemodialysis access.

PMID- 15466788
TI  - Venous access for patients with chronic kidney disease.

PMID- 15466789
TI  - Large asymptomatic hydropneumothorax after thoracentesis.
AB  - The interventional radiology Case Corner Series is a new feature that will be
      presented quarterly in JVIR. The format is uniquely designed for the busy
      interventional radiology practitioner. Case presentations are short and to the
      point. Discussions are succinct and pertinent to current practice. Each quarter,
      a difficult or problem case is presented and the reader is challenged with
      questions relevant to the case. Short answers are then provided based on
      referenced sources from the current literature. Cases are drawn from the
      interventional radiology experience at the University of California San Francisco
      and are edited by Jeanne M. LaBerge, MD, and Robert K. Kerlan, Jr, MD.

PMID- 15466790
TI  - SMART stent for salvage of hemodialysis access grafts.
AB  - PURPOSE: To evaluate the SMART stent for treating angioplasty-resistant
      hemodialysis access venous stenoses. MATERIALS AND METHODS: A retrospective study
      of 64 patients with polytetrafluoroethylene grafts who were treated with the
      SMART stent at 69 locations in the venous outflow tract was undertaken. Stents
      were used for elastic recoil after percutaneous transluminal angioplasty, venous
      rupture, or recurrent stenosis less than 3 months after angioplasty. When
      angiographic follow-up was available, the degree of in-stent restenosis was
      measured. Primary patency was determined, and, when applicable, compared with
      that of previous angioplasty treatments of the same lesion. RESULTS: The SMART
      stent was placed in 15 central veins and 54 peripheral veins, with a 98%
      technical success rate and a 97% clinical success rate. The mean primary access
      patency times were 14.9 months and 8.9 months in patients who received central
      and peripheral stents, respectively. In 19 patients whose central or peripheral
      venous stenoses were previously treated with angioplasty, the mean primary access
      patency was increased from 2.5 months to 10.6 months after placement of the SMART
      stent (P = .0003). Angiography in 29 patients after an average of 348 days showed
      55% mean in-stent stenosis. The only stent-related complication occurred in a
      patient who had venous dissection associated with the edge of a SMART stent
      placed at the elbow. CONCLUSION: The SMART stent is safe and effective for
      treating dialysis access venous stenoses that are resistant to standard
      angioplasty.

PMID- 15466791
TI  - Greater energy delivery improves treatment success of endovenous laser treatment
      of incompetent saphenous veins.
AB  - PURPOSE: Early and midterm results of endovenous laser treatment (EVLT) of the
      saphenous veins for the treatment of symptomatic insufficiency are promising.
      However, technical factors contributing to success or failure of saphenous vein
      EVLT have not been fully investigated. This study was performed to test the
      hypothesis that treatment success is related to achieving a critical threshold of
      energy delivery relative to the length of vein treated. MATERIALS AND METHODS:
      Data regarding length of treated vein and total energy delivered were collected
      from prospectively acquired databases at two institutions. Ultrasound (US)
      examinations were obtained for all treated veins. Successful EVLT was defined as
      US-documented absence of flow in the treated vein. EVLT failure was defined by US
      evidence of flow at any point in the treated vein segment at any time more than 1
      week after the treatment date. A two-tailed Student t test was performed for
      statistical analysis and the null hypothesis was rejected at a P value less than
      .05. RESULTS: One hundred eleven treated veins were followed up with US over 3-78
      weeks (mean, 29.5 weeks). During this time, 85 treated veins (77.5%) remained
      closed. In this group of successfully treated veins, average energy delivered was
      63.4 J/cm (range, 20.5-137.8 J/cm). The average energy delivered to the 26 veins
      (22.5%) in the failure group was 46.6 J/cm (range, 25.7-78 J/cm). This difference
      in delivered energy was statistically significant (P < .0001). No treatment
      failures were identified in patients who received doses of 80 J/cm or more.
      CONCLUSION: EVLT is an effective method of incompetent saphenous vein treatment.
      Greater doses of energy delivered are associated with successful EVLT,
      particularly when doses of more than 80 J/cm are delivered.

PMID- 15466792
TI  - In-hospital costs of self-expanding nitinol stent implantation versus balloon
      angioplasty in the femoropopliteal artery (the VascuCoil Trial).
AB  - PURPOSE: Although several prospective studies have examined the safety and
      efficacy of stent placement for femoropopliteal arterial disease, the current
      cost of these procedures is unknown. To estimate and compare hospital costs
      associated with conventional balloon angioplasty (percutaneous transluminal
      angioplasty [PTA]) and stent placement for patients with symptomatic peripheral
      arterial disease, the authors performed a prospective economic evaluation in
      conjunction with the Intracoil Femoropopliteal Stent Trial (VascuCoil). MATERIALS
      AND METHODS: Between May 1997 and December 1999, 266 patients with stenotic or
      occluded superficial femoral or popliteal arteries were prospectively randomized
      to treatment with the IntraCoil stent or PTA. Detailed resource use and cost data
      for each patient's initial revascularization procedure and ensuing
      hospitalization were collected and analyzed on an intention-to-treat basis.
      RESULTS: Compared with conventional balloon angioplasty, stent placement did not
      improve clinical outcomes but increased procedure duration, equipment costs, and
      physician services. As a result, initial hospital costs were approximately 3,500
      dollars higher for patients randomized to the IntraCoil stent, compared with PTA
      (8,435 dollars vs 4,980 dollars; P < .001). CONCLUSIONS: As performed in the
      VascuCoil trial, primary stent placement for femoropopliteal disease did not
      improve clinical outcomes but increased initial treatment costs by more than
      3,000 dollars. Because there were no substantial differences in subsequent
      clinical outcomes between the two treatments, it is unlikely that these increased
      initial costs would be offset by savings in follow-up costs. These findings
      suggest that a strategy of routine stent implantation for patients undergoing
      femoropopliteal PTA is not optimal on economic grounds and that PTA with
      provisional stent implantation is preferred.

PMID- 15466793
TI  - Peripheral high-flow arteriovenous vascular malformations: a single-center
      experience.
AB  - PURPOSE: To assess the long-term outcomes of patients with high-flow
      arteriovenous malformations (HFAVMs) of the extremities. MATERIALS AND METHODS: A
      retrospective review was performed to identify patients with HFAVMs referred for
      possible intervention between 1988 and 2003. Sixteen patients with upper-limb
      HFAVMs and 15 patients with lower-limb HFAVMs were identified (18 men, 13 women;
      mean age, 36.8 years; range, 21.1-72.2 years). Arteriography, duplex imaging
      studies, or magnetic resonance imaging were performed in all patients. RESULTS:
      Follow-up was completed in 30 patients (mean duration, 3.3 years; range, 0.2-13
      years), with one patient lost to follow-up. Nineteen had symptoms that warranted
      endovascular treatment: 13 underwent embolotherapy and six were considered
      unsuitable because of challenging anatomy that rendered embolization unsafe or
      impossible. Eleven patients' symptomatology did not warrant treatment and these
      patients were treated conservatively. The 13 patients treated with embolotherapy
      underwent a total of 27 treatment sessions (mean, 2.1 sessions per patient;
      range, 1-5). N-butyl cyanoacrylate and polyvinyl alcohol were used as the embolic
      agent in 11 and two patients, respectively. Three patients had complete
      resolution of HFAVM clinically and angiographically, and five patients' symptoms
      were controlled despite persistence of the HFAVM angiographically. Five patients
      had no improvement after treatment. Two major complications occurred (7.4% per
      session or 15.4% per patient): one patient developed a tibial plateau compression
      fracture and one patient had temporary L5 neuropathy after embolization of the
      pelvis and thigh. Of the six patients who were considered unsuitable for
      embolotherapy, one patient died of hepatocellular carcinoma, two had significant
      progression of symptoms, and the remaining three patients' symptomatology was
      unchanged. Only one of the nine patients with mild symptoms at presentation had
      symptom progression during follow-up. CONCLUSIONS: Peripheral HFAVM is a rare and
      therapeutically challenging condition. Patients with minimal symptoms at
      presentation do well with conservative treatment, and symptomatic progression is
      infrequent. Only patients with significant symptomatology should undergo
      embolization therapy, which invariably requires multiple sessions and must be
      aimed at eradication of the nidus.

PMID- 15466794
TI  - Angiographic assessment of initial balloon angioplasty results.
AB  - PURPOSE: To determine the influence of three factors involved in the angiographic
      assessment of balloon angioplasty-interobserver variability, operator bias, and
      the definition used to determine success-on the primary (technical) results of
      angioplasty in the peripheral arteries. MATERIALS AND METHODS: Percent stenosis
      in 107 lesions in lower-extremity arteries was graded by three independent,
      experienced vascular radiologists ("observers") before and after balloon
      angioplasty and their estimates were compared with the initial interpretations
      reported by the physician performing the procedure ("operator") and an automated
      quantitative computer analysis. Observer variability was measured with use of
      intraclass correlation coefficients and SD. Differences among the operator,
      observers, and the computer were analyzed with use of the Wilcoxon signed-rank
      test and analysis of variance. For each evaluator, the results in this series of
      lesions were interpreted with three different definitions of success. RESULTS:
      Estimation of residual stenosis varied by an average range of 22.76% with an
      average SD of 8.99. The intraclass correlation coefficients averaged 0.59 for
      residual stenosis after angioplasty for the three observers but decreased to 0.36
      when the operator was included as the fourth evaluator. There was good to very
      good agreement among the three independent observers and the computer, but poor
      correlation with the operator (P </= .001). The primary success rates for this
      series of lesions varied from a low of 47% to high of 99%, depending solely on
      which definition of success was used. Significant differences among the operator,
      the three observers, and the computer were not present when the definition of
      success was based on less than 50% residual stenosis. CONCLUSIONS: Observer
      variability and bias in the subjective evaluation of peripheral angioplasty can
      have a significant influence on the reported initial success rates. This effect
      can be largely eliminated with the use of residual stenosis of less than 50% to
      define success. Otherwise, meaningful evaluation of angioplasty results will
      require independent panels of evaluators or computerized measurements.

PMID- 15466795
TI  - Catheter position for adequate intra-arterial chemotherapy for advanced
      pancreatic cancer: evaluation with CT during arterial injection of contrast
      material.
AB  - PURPOSE: To identify the drug infusion vessel for use in obtaining the best drug
      distribution in arterial infusion chemotherapy for advanced pancreatic cancer.
      MATERIALS AND METHODS: In 16 cases of advanced pancreatic cancer (pancreatic
      head, n = 12; pancreatic body and/or tail, n = 4), computed tomography during
      arterial injection of contrast material was performed at the time of angiography.
      The sites of catheter placement were celiac artery, superior mesenteric artery,
      and their branches, such as gastroduodenal artery, inferior pancreatico-duodenal
      artery, or dorsal pancreatic artery. RESULTS: In the cases of pancreatic head
      cancer, all except one with hepatomesenteric vascular variation were supplied by
      the celiac artery and superior mesenteric artery (dual supply). In the cases of
      pancreatic body and/or tail cancer, two were supplied by celiac artery alone and
      two showed dual supply. In the cases of pancreatic head cancer, when the areas
      supplied by the main trunk were compared with those supplied by its branches,
      three of nine cases on the celiac artery side and four cases on the superior
      mesenteric artery side showed that the areas were not consistent, with a partial
      defect observed in the areas supplied by branches of the superior mesenteric
      artery. In the cases of pancreatic body and/or tail cancer, on both sides, one of
      two cases was not consistent. CONCLUSIONS: To achieve optimal drug distribution
      in arterial infusion chemotherapy for advanced pancreatic cancer, drug infusion
      via both the celiac artery and superior mesenteric artery is required in the
      majority of cases. In many cases, optimal drug distribution is not attainable
      with drug infusion via a branch; therefore, drug infusion should be administered
      via the main trunk.

PMID- 15466796
TI  - CT-guided transvenous or transcaval needle biopsy of pancreatic and
      peripancreatic lesions.
AB  - PURPOSE: To evaluate the safety and efficacy of direct computed tomography (CT)
      guided fine needle aspiration biopsy (FNAB) of pancreatic and peripancreatic
      masses via a posterior approach that traverses the inferior vena cava (IVC) or
      renal vein. MATERIALS AND METHODS: From January 2000 to July 2003, 55 patients
      underwent 58 biopsies of masses located within the pancreas (n = 28) or in a
      peripancreatic location (n = 30) with use of a posterior approach that crossed
      the IVC or renal vein. Biopsies were performed with needles ranging in size from
      18 to 22. Cytology reports and medical records of all patients were
      retrospectively reviewed to evaluate diagnostic accuracy and complication rates.
      RESULTS: Masses were safely accessed with a direct (noncoaxial) pathway
      traversing the IVC (n = 54), renal vein (n = 4), or both (n = 3). Overall
      diagnostic accuracy was 86% (50 of 58). Cytologic examination was positive for
      malignancy in 39 of 58 biopsies (67%). Benign lesions were demonstrated in 12 of
      58 biopsies. In seven cases (12%), the sample was deemed nondiagnostic. Of those,
      four were diagnosed later by endoscopy (n = 1), surgical biopsy (n = 2), or
      repeat FNAB (n = 1). A false-negative result was noted in one case, which was
      later diagnosed by repeat biopsy. A total of four inadvertent passes through the
      right renal artery were recorded. CT evidence of perilesional blood was seen in
      eight of 55 patients (eight of 58 cases). Three of these occurred after a passage
      via the right renal artery. All patients remained asymptomatic, and no
      transfusion or change in management was necessary. No other complications
      occurred. CONCLUSION: CT-guided noncoaxial FNAB with an approach that traverses
      the IVC or renal vein is safe and effective in obtaining diagnostic specimens
      from pancreatic and peripancreatic masses.

PMID- 15466797
TI  - Measurement of portal blood and transjugular intrahepatic portosystemic shunt
      flow with use of a retrograde thermodilutional catheter.
AB  - PURPOSE: Direct blood flow measurement in the portal vein (PV) and in
      transjugular intrahepatic portosystemic shunts (TIPS) holds potential as a means
      of optimizing shunt creation and predicting outcomes. A retrograde
      thermodilutional flow measurement catheter was recently designed. The purpose of
      this study was to validate and optimize the technique of blood flow measurement
      in the PV with use of this catheter in a swine model of TIPS. MATERIALS AND
      METHODS: Six domestic swine underwent TIPS creation. At day 14, shunts were
      catheterized for venography and portal blood flow measurement with use of
      thermodilutional catheters. Simultaneous flow measurements were made with use of
      the thermodilutional and perivascular methods at the same anatomic location
      within the PV. To test reproducibility of the flow measurement, repeated
      measurements were performed in the PV and shunt. RESULTS: Fifty-five measurements
      of PV blood flow with the thermodilutional catheter and perivascular probe were
      made in five animals. Perivascular probe placement was unsuccessful in one
      animal. There was high correlation between the thermodilutional and perivascular
      measurements (r(2) = 0.96; Q(periv) = 0.80 . Q(therm) + 147 mL/min; n = 55;
      range, 205-1541 mL/min). The difference between two consecutive thermodilutional
      measurements and their mean was less than 50 mL/min in 72% of measurements and
      less than 100 mL/min in 94% of measurements (N = 85 pairs). CONCLUSIONS:
      Measurement of PV blood flow with use of a retrograde thermodilutional catheter
      system yields reliable and reproducible results. This catheter system holds
      promising utility as a device for measuring flow within TIPS and the PV.

PMID- 15466798
TI  - Hybrid radiofrequency and cryoablation device: preliminary results in an animal
      model.
AB  - PURPOSE: To determine whether the simultaneous application of combined bipolar
      radiofrequency (RF) ablation and cryoablation in a hybrid system produces larger
      ablation zones than RF or cryoablation alone. MATERIALS AND METHODS: Multiple 15
      minute ablations were performed in ex vivo bovine liver (n = 167) with a hybrid
      applicator system with RF ablation alone (0.3-0.7 A), cryoablation alone (3,500
      psi, two freeze/thaw cycles), and combined RF/cryoablation (0.4-0.7 A, 1,000
      3,500 psi) with use of a novel applicator consisting of two 2.5-cm active bipolar
      RF poles located on the same 18-gauge needle separated by two embedded
      cryoablation nozzles. Resultant coagulation diameters were compared with use of
      analysis of variance for more than three groups or Student t tests for two
      groups. Confirmation of the optimal parameters of combination RF/cryoablation was
      performed by reassessing a range of argon pressure (1,000-3,500 psi) and RF
      current (0.4-0.7 A) in in vivo porcine liver (n = 36). Arrays of two to four
      RF/cryoablation applicators were also assessed in ex vivo (n = 54) and in vivo (n
      = 12) liver. RESULTS: In ex vivo liver, simultaneous RF/cryoablation (0.6 A,
      3,000 psi) produced 3.6 cm +/- 0.4 of short-axis coagulation. This was
      significantly larger than that achieved with optimal RF alone or cryoablation
      alone (1.5 cm +/- 0.3 and 1.6 cm +/- 0.3, respectively; F = 95; P < .01). The
      coagulation diameter with simultaneous combination RF/cryoablation was related in
      parabolic fashion to argon pressure and current with a multivariate r(2) of 0.68.
      For in vivo liver, optimal combination RF/cryoablation achieved 3.3 cm +/- 0.2 of
      coagulation, which was significantly larger than that achieved with RF alone (1.1
      cm +/- 0.1; P < .01) or cryoablation alone (1.1 cm +/- 0.1 and 1.3 cm +/- 0.1; F
      = 203; P < .01). The greatest contiguous coagulation was achieved with multiple
      applicator arrays. For ex vivo liver, short-axis coagulation measured 5.3 cm +/-
      0.1, 6.4 cm +/- 0.1, and 7.6 cm +/- 0.1 for two-, three-, and four-applicator
      arrays, respectively. For in vivo liver, two-, three-, and four-applicator arrays
      produced 5.1 cm +/- 0.2, 5.8 cm +/- 0.5, and 7.0 cm +/- 0.5 of confluent
      coagulation, respectively. CONCLUSION: Simultaneous combination RF and
      cryoablation with use of a novel applicator design yielded significantly larger
      zones of coagulation than either modality alone. The large ablation diameters
      achieved warrant further investigation of the device.

PMID- 15466799
TI  - Transcatheter arterial embolization with 188Rhenium-HDD-labeled iodized oil in
      rabbit VX2 liver tumor.
AB  - PURPOSE: To evaluate the antitumor effect of transcatheter arterial embolization
      (TAE) with use of rhenium 188 HDD (4-hexadecyl 2,2,9,9-tetramethyl-4,7-diaza-1,10
      decanethiol)-labeled iodized oil and to compare it with that of transcatheter
      arterial chemoembolization (TACE) with use of an established chemotherapeutic
      agent and iodized oil in experimentally induced liver tumor. MATERIALS AND
      METHODS: VX2 carcinoma was grown in the livers of 57 rabbits. TAE was performed
      with (188)Re-HDD-labeled iodized oil (Re-Lp group; n = 21), doxorubicin/iodized
      oil emulsion (Dx-Lp group; n = 21), and iodized oil alone (n = 15). Sequential
      conjugated planar imaging was performed for dosimetry of the radioisotope in the
      Re-Lp group (n = 15). Growth ratio and percentage of viable tumor were estimated
      by computed tomography and histopathologic examination. Hepatic and hematologic
      toxicities were evaluated by biochemical analysis. RESULTS: On conjugated planar
      imaging, radioactivity was concentrated on the tumor (effective half-life, 16.2
      hours), and mean radiation dose to the tumor was 147.7 Gy. The mean growth ratios
      1, 2, and 3 weeks after TAE and the percentage of viable tumor in the Re-Lp group
      (-3.4, -7.6, -11.1, and 0.3%) and the Dx-Lp group (-3.2, -5.3, 29.0, and 2.6%)
      were significantly lower than the respective values in the iodized oil group
      (45.5, 145.4, 283.0, and 30.1%; P < .001). However, the differences between the
      values in the Re-Lp group and those in the Dx-Lp group were not significant (P
      values of .165-0.497 for growth ratios; P = .134 for percentage of viable tumor).
      There was similar transient hepatotoxicity in all three groups. CONCLUSIONS: TAE
      with (188)Re-HDD-labeled iodized oil has potent antitumor effect in VX2 liver
      tumor that is comparable with that of TACE with an established chemotherapeutic
      agent.

PMID- 15466800
TI  - Comparison of percutaneous management techniques for recurrent malignant ascites.
AB  - The Pleurx subcutaneous tunneled catheter is approved for repeated, long-term
      drainage of malignant pleural effusions; however, there is limited literature
      describing its use in malignant ascites. The authors compared the safety and
      efficacy of two percutaneous drainage methods: large volume paracentesis and
      Pleurx catheter placement over a 41-month period. The Pleurx catheter provided
      effective palliation with a complication rate similar to that for large volume
      paracentesis, while preventing the need for frequent trips to the hospital for
      repeated percutaneous drainage.

PMID- 15466801
TI  - Value of multislice CT in the diagnosis of pulmonary artery pseudoaneurysm from
      Swan-Ganz catheter placement.
AB  - Perforation of a pulmonary artery after placement of a Swan-Ganz catheter is a
      serious complication that requires immediate management. Exact description of
      size and anatomic localization of a pulmonary pseudoaneurysm is crucial for
      planning further therapy. This report describes a patient who experienced such a
      complication, but in whom primary pulmonary angiography failed to demonstrate
      bleeding. However, multislice computed tomography not only correctly demonstrated
      the anatomic location of the pseudoaneurysm but was also able to directly
      visualize the feeder vessel and its connection to the aneurysm. This information
      was essential for subsequent superselective angiographic visualization of the
      feeder vessel and for successful embolization as the least invasive method of
      choice.

PMID- 15466802
TI  - Displacement of endoscopically placed plastic biliary endoprostheses into the
      duodenum with a simple transhepatic technique.
AB  - The authors to describe the technique and report the results of percutaneous
      displacement of endoscopically placed plastic biliary endoprostheses into the
      duodenum at the time of transhepatic intervention in 34 patients. Displacement
      into the duodenum was effected by simply passing a guide wire through the stent,
      and then pushing it into the gut with a catheter. Thirty-three of 36 stents (92%)
      were successfully displaced in this manner. No complications related to stent
      passage out of the gastrointestinal tract were encountered. Plastic biliary
      stents can be safely displaced into the duodenum when patients undergo
      transhepatic biliary procedures, thus avoiding repeated endoscopy.

PMID- 15466803
TI  - Endovascular treatment of a giant intracranial aneurysm with a stent-graft.
AB  - This report describes a giant intracavernous carotid aneurysm successfully
      treated by the placement of a single covered stent. A 40-year-old woman was
      admitted with a progressive diplopia in relation with palsy of the IV and VI
      cranial nerves. Magnetic resonance imaging revealed an intracavernous giant
      aneurysm located at the bifurcation between the origin of a trigeminal artery and
      the intracavernous portion of the right internal carotid artery. A covered stent
      was successfully placed, and complete exclusion of the aneurysm was confirmed at
      11-month follow-up angiography. The use of covered stents in intracranial
      vascular structures can now be a feasible way of treating selected cases of wide
      necked intracranial aneurysms.

PMID- 15466804
TI  - Stent-graft treatment of extracranial carotid and vertebral arterial lesions.
AB  - Five patients with pseudoaneurysms of the carotid artery (n = 4) and an
      arteriovenous fistula of the vertebral artery (n = 1) were treated with stent
      grafts. Commercially made devices were used in all but one of the patients. In
      four of the five patients, the pathology was successfully excluded. One patient
      had a small type-I endoleak. There were no immediate procedure-related
      complications or neurologic sequalae. All experienced immediate resolution of
      symptoms. One patient was lost to follow-up after discharge and another died 2
      weeks after intervention. The remaining patients remained asymptomatic with
      patent stent-grafts after follow-up periods of 14, 16, and 46 months,
      respectively.

PMID- 15466805
TI  - Extracorporeal expulsion of a vascular endograft used to treat a mycotic
      aneurysm.
AB  - A 65-year-old woman with a right common iliac artery mycotic aneurysm and an
      overlying sacral pressure ulcer was treated with placement of a vascular
      endograft. The mycotic aneurysm was successfully excluded, but 3 months after the
      procedure, the endograft was expelled through the wound. Fortunately, the patient
      had minimal clinical sequelae. This case emphasizes the importance of frequent
      noninvasive imaging of mycotic aneurysms treated with endografts. A rigorous
      postoperative imaging protocol is proposed based on the current regimen for
      abdominal aortic aneurysm surveillance after endograft implantation.

PMID- 15466806
TI  - CO2 splenoportography for evaluating the splenic and portal veins before or after
      liver transplantation.
AB  - The authors report their experience with CO(2) splenoportography in a
      retrospective review of 15 studies performed in 13 patients before or after liver
      transplantation. The studies were performed by injecting CO(2) through a small
      caliber needle introduced into the splenic parenchyma with ultrasound guidance
      and imaging with conventional digital subtraction techniques. The findings were
      compared with clinical follow-up and other imaging studies when available. Eight
      of the 15 studies were normal, of which two were confirmed by additional studies.
      Six of the 15 studies were abnormal, all of which were compared with additional
      studies. There was one nondiagnostic study and two false positives. There were no
      reported complications. The authors' experience suggests that CO(2)
      splenoportography is a minimally invasive method for safely and accurately
      evaluating the splenic and portal veins.

PMID- 15466807
TI  - Routine peripherally inserted central catheter placement resulting in delayed
      intravascular foreign body.

PMID- 15466808
TI  - Retrieval of the Bard recovery filter from the superior vena cava.

PMID- 15466809
TI  - Re: modified monorail technique for insertion of tunneled hemodialysis catheters.

PMID- 15466810
TI  - Analysis of slow hyperpolarizing potentials in frog taste cells induced by
      glossopharyngeal nerve stimulation.
AB  - Electrical stimulation of the frog glossopharyngeal (GP) nerve evoked slow
      hyperpolarizing potentials (HPs) in taste cells. This study aimed to clarify
      whether slow HPs were postsynaptically induced in taste cells. The slow HPs were
      recorded intracellularly with a microelectrode. When Ca2+ concentration in the
      blood plasma was decreased to approximately 0.5 mM, the amplitude of slow HPs
      reduced and their latency lengthened. When the Ca2+ concentration was increased
      to approximately 20 mM, the amplitude of slow HPs increased and their latency
      shortened. Addition of Cd2+ to the plasma greatly reduced the amplitude of slow
      HPs and lengthened their latency. These data suggest that the slow HPs are
      dependent on presynaptic activities in the GP nerve terminals in the taste disk.
      Of various antagonists injected intravenously for blocking receptors of
      neurotransmitter biogenic amines and peptides, only antagonists for substance P
      blocked the slow HPs at 2-4 mg/kg body wt. Application of substance P of 2 mg/kg
      to the plasma induced hyperpolarizing responses in taste cells, whose amplitude
      was the same as that of the slow HPs induced by GP nerve stimulation. Application
      of a nonselective cation channel antagonist, flufenamic acid, to the plasma
      blocked the slow HPs. These results suggest that the slow HPs are generated by
      closing the nonselective cation channels in the postsynaptic membrane of taste
      cells following possible release of substance P from the GP nerve terminals in
      the taste disk.

PMID- 15466812
TI  - Effect of concentration on taste-taste interactions in foods for elderly and
      young subjects.
AB  - An increase in concentration of one of the tastants in a 'real food' might affect
      not only the perception of the taste quality of that manipulated tastant but also
      the other perceivable taste qualities. The influence of concentration increase of
      sodium or potassium chloride in tomato soup, sucrose or aspartame in iced tea,
      acetic or citric acid in mayonnaise, caffeine or quinine HCl in chocolate drink,
      monosodium glutamate (MSG) or inosine 5'-monophosphate (IMP) in broth on the
      other perceivable taste qualities in these foods was studied in 21 young subjects
      (19-33 years) and 21 older subjects (60-75 years). The results showed that for
      each of these tastants, except for the two acids, increasing the concentration
      provoked significant positive or negative interaction effects on the perception
      of one or more other taste qualities of the product. Especially in the young,
      olfaction plays a larger role in the assessment of taste intensity than has been
      hitherto assumed. The elderly are less able to discriminate between the taste
      qualities in a product, whereas the young are more able to do so.

PMID- 15466811
TI  - Effects of vomeronasal organ removal on olfactory sex discrimination and odor
      preferences of female ferrets.
AB  - Previous research suggests that body odorants, including anal scents and urinary
      odors, contribute to sex discrimination and mate identification in European
      ferrets of both sexes. We assessed the possible role of the vomeronasal organ
      (VNO) in these functions by surgically removing the organ bilaterally in sexually
      experienced female ferrets. Lesioned (VNOx) and sham-operated control (VNOi)
      females reliably discriminated between male- and female-derived anal scent gland
      as well as fresh urinary odors in habituation/dishabituation tests. However, VNOi
      females spent significantly more time than VNOx subjects investigating male
      urinary odors in these tests. Also, VNOi females, but not VNOx subjects,
      preferred to investigate day-old male versus female urine spots as well as wooden
      blocks that had previously been soiled by male versus female ferrets. Both groups
      of female ferrets preferred to approach volatile odors from a breeding male
      instead of an estrous female in Y-maze tests and both groups showed similar
      levels of receptive sexual behavior in response to a male's neck grip. The VNO is
      apparently not required for olfactory sex discrimination or mate recognition in
      this carnivore, but instead may play a role in promoting continued contact with
      nonvolatile body odors previously deposited by opposite-sex conspecifics during
      territorial scent marking.

PMID- 15466813
TI  - Laryngeal chemosensory clusters.
AB  - The expression of molecules involved in the transductory cascade of the sense of
      taste (TRs, alpha-gustducin, PLCbeta2, IP3R3) has been described in lingual taste
      buds or in solitary chemoreceptor cells located in different organs. At the
      laryngeal inlet, immunocytochemical staining at the light and electron microscope
      levels revealed that alpha-gustducin and PLCbeta2 are mainly localized in
      chemosensory clusters (CCs), which are multicellular organizations differing from
      taste buds, being generally composed of two or three chemoreceptor cells.
      Compared with lingual taste buds, CCs are lower in height and smaller in
      diameter. In laryngeal CCs, immunocytochemistry using the two antibodies
      identified a similar cell type which appears rather unlike the alpha-gustducin
      immunoreactive (IR) and PLCbeta2-IR cells visible in lingual taste buds. The
      laryngeal IR cells are shorter than the lingual ones, with poorly developed basal
      processes and their apical process is shorter and thicker. Some cells show a
      flask-like shape due to the presence of a large body and the absence of basal
      processes. CCs lack pores and their delimitation from the surrounding epithelium
      is poorly evident. The demonstration of the existence of CCs strengthens the
      hypothesis of a phylogenetic link between gustatory and solitary chemosensory
      cells.

PMID- 15466814
TI  - High-resolution magnetic resonance spectroscopy of the mouse vomeronasal organ.
AB  - The chemical composition of the vomeronasal organ (VNO) was investigated by means
      of in vitro proton magnetic resonance spectroscopy (MRS) in prepubertal and adult
      mice of both sexes. Results demonstrate that MRS detects several chemical
      constituents in the VNO, showing their age- and sex-associated changes in
      concentration. Preliminary experiments also suggest the ability of MRS to show
      compositional changes in the VNO after pheromonal stimulation. MRS can serve as a
      useful technique to investigate vomeronasal chemoreception.

PMID- 15466815
TI  - Bitter taste study in a sardinian genetic isolate supports the association of
      phenylthiocarbamide sensitivity to the TAS2R38 bitter receptor gene.
AB  - Recently, a major locus on chromosome 7q was found in association with the taste
      sensitivity to phenylthiocarbamide (PTC) in humans. This region contains the
      TAS2R38 gene that encodes a member of the TAS2R bitter taste receptor family.
      Three SNPs within this gene demonstrated a strong association with taster status
      in Utah families and in an additional sample of 85 unrelated individuals. We
      studied a small isolated village in eastern Sardinia and carried out a genome
      wide scan to map the genetic basis of PTC perception in this population. We
      performed both qualitative and quantitative PTC-taste linkage analysis.
      Qualitative analysis was carried out by defining a cut-off from the bimodal
      distribution of the trait and classifying subjects as tasters and non-tasters (75
      and 25%, respectively). Linkage analysis on 131 subjects belonging to a unique
      large multi-generation pedigree comprising 239 subjects confirmed significant
      evidence for linkage at 7q35 also in our population. Haplotype analyses of the
      three SNPs inside the PTC gene allowed us to identify only two haplotypes that
      were associated with the non-taster phenotype (80% AVI homozygous) and to taster
      phenotype (40% PAV homozygous and 56% PAV/AVI heterozygous). Sex, age and
      haplotype effect explained 77.2 % of the total variance in PTC sensitivity.

PMID- 15466816
TI  - A specific receptor site for glycerol, a new sweet tastant for Drosophila:
      structure-taste relationship of glycerol in the labellar sugar receptor cell.
AB  - Glycerol, a linear triol, is a sweet tastant for mammals but it has not
      previously been recognized to stimulate the sense of taste in insects. Here we
      show by electrophysiological experimentation that it effectively stimulates the
      labellar sugar receptor cell of Drosophila. We also show that in accord with the
      electrophysiological observations, the behavioral feeding response to glycerol is
      dose dependent. 3-Amino-1,2-propanediol inhibited the response of the sugar
      receptor cell to glycerol, specifically and competitively, while it had almost no
      effect on responses to sucrose, D-glucose, D-fructose and trehalose. In the null
      Drosophila mutant for the trehalose receptor (DeltaEP19), the response to
      glycerol showed no change, in sharp contrast with a characteristic drastic
      decrease in the response to trehalose. The glycerol concentration-response curves
      for I-type and L-type labellar hairs were statistically indistinguishable, while
      those for sucrose, D-glucose, D-fructose and trehalose were clearly different.
      These all indicate the presence of a specific receptor site for glycerol. The
      glycerol site was characterized by comparing the effectiveness of various
      derivatives of glycerol. Based on this structure-taste relationship of glycerol,
      a model is proposed for the glycerol site including three subsites and two steric
      barriers, which cannot accommodate carbon-ring containing sugars such as D
      glucose.

PMID- 15466817
TI  - Sour taste preferences of children relate to preference for novel and intense
      stimuli.
AB  - Previous research has suggested that some children have a preference for sour
      tastes. The origin of this preference remains unclear. We investigated whether
      preference for sour tastes is related to a difference in rated sour intensity due
      to physiological properties of saliva, or to an overall preference for intense
      and new stimuli. Eighty-nine children 7-12 years old carried out a rank-order
      procedure for preference and category scale for perceived intensity for four
      gelatins (i.e. 0.0 M, 0.02 M, 0.08 M, 0.25 M added citric acid) and four yellow
      cards that differed in brightness. In addition, we measured their willingness to
      try a novel candy and their flow and buffering capacity of their saliva. Fifty
      eight percent of the children tested preferred one of the two most sour gelatins.
      These children had a higher preference for the brightest color (P < 0.05) and
      were more likely to try the candy with the unknown flavor (P < 0.001) than
      children who did not prefer the most sour gelatins. Preference for sour taste was
      not related with differences in rated sour intensity, however those who preferred
      sour taste had a higher salivary flow (P < 0.05). These findings show that a
      substantial proportion of young children have a preference for extreme sour
      taste. This appears to be related to the willingness to try unknown foods and
      preference for intense visual stimuli. Further research is needed to investigate
      how these findings can be implemented in the promotion of sour-tasting food such
      as fruit.

PMID- 15466818
TI  - Monosodium glutamate and sweet taste: discrimination between the tastes of sweet
      stimuli and glutamate in rats.
AB  - Generalization of a conditioned taste aversion (CTA) is based on similarities in
      taste qualities shared by the aversive substance and another taste substance. CTA
      experiments with rats have found that an aversion to a variety of sweet stimuli
      will cross-generalize with monosodium glutamate (MSG) when amiloride, a sodium
      channel blocker, is added to all solutions to reduce the taste of sodium. These
      findings suggest that the glutamate anion elicits a sweet taste sensation in
      rats. CTA experiments, however, generally do not indicate whether two substances
      have different taste qualities. In this study, discrimination methods in which
      rats focused on perceptual differences were used to determine if they could
      distinguish between the tastes of MSG and four sweet substances. As expected,
      rats readily discriminated between two natural sugars (sucrose, glucose) and two
      artificial sweeteners (saccharin, SC45647). Rats also easily discriminated
      between MSG and glucose, saccharin and, to a lesser extent, SC45647 when the
      taste of the sodium ion of MSG was reduced by the addition of amiloride to all
      solutions, or the addition of amiloride to all solutions and NaCl to each sweet
      stimulus to match the concentration of Na+ in the MSG solutions. In contrast,
      reducing the cue function of the Na+ ion significantly decreased their ability to
      discriminate between sucrose and MSG. These results suggest that the sweet
      qualities of glutamate taste is not as dominate a component of glutamate taste as
      CTA experiments suggest and these qualities are most closely related to the taste
      qualities of sucrose. The findings of this study, in conjunction with other
      research, suggest that sweet and umami afferent signaling may converge through a
      taste receptor with a high affinity for glutamate and sucrose or a downstream
      transduction mechanism. These data also suggest that rats do not necessarily
      perceive the tastes of these sweet stimuli as similar and that these sweet
      stimuli are detected by multiple sweet receptors.

PMID- 15466819
TI  - Lateralization of olfactory processes.
AB  - Over the last ten years, methods of cerebral imaging have revolutionized our
      knowledge of cognitive processes in humans. An impressive number of papers
      dealing with cerebral imaging for olfaction have been published to date. Whereas
      the early works revealed those structures participating in the processing of
      odours presented passively to subjects, researchers later recorded brain activity
      when subjects performed specific olfactory tasks based on memory, emotion and
      identification. From these results, we suggest that there is a dissociation of
      olfactory processes, with involvement of the right hemisphere in memory processes
      and the left hemisphere in emotional processes. The review concludes with a
      summary of how these lateralized processes are consistent with the gestalt-nature
      of our olfactory perception.

PMID- 15466821
TI  - The synergistic cytotoxicity of cisplatin and taxol in killing oral squamous cell
      carcinoma.
AB  - BACKGROUND: Platinum, 5-fluorouracil (5-FU) and taxanes are commonly used in
      chemotherapeutic modalities of various carcinomas. However, taxanes are rarely
      used in patients suffering from head and neck squamous cell carcinoma (HNSCC) in
      Taiwan. The purpose of this study was to assess whether there is a synergistic
      effect produced by incorporating Taxol (paclitaxel) with cisplatin, carboplatin
      or 5-FU in the combined treatment of oral squamous cell carcinoma (OSCC).
      METHODS: OSCC cells were surgically excised from a Taiwanese patient and cultured
      into a cell line, OECM-1. The viability of OECM-1 after drug treatment was
      determined by an XTT labeling reagent. RESULTS: The dose-dependent cytotoxicity
      of each drug was determined. The order of chemosensitivity of OECM-1 toward these
      drugs was Taxol, cisplatin, carboplatin and 5-FU, with 50% inhibitory
      concentrations (IC(50)s) of 10, 68, 332 and 3000 microM, respectively. In the
      combined drug treatment, low concentrations of platinum (10 microM) or 5-FU (500
      microM) were included in the culture media with low cytotoxic concentrations of
      Taxol (0.025, 0.05 and 0.1 microM). When combined with 0.025 microM of Taxol,
      only cisplatin, rather than carboplatin and 5-FU, showed synergistic cytotoxicity
      with OECM-1. Cisplatin also acted synergistically with 0.05 and 0.1 microM of
      Taxol. On the other hand, carboplatin and 5-FU acted additively with low
      cytotoxic concentrations of Taxol (0.025, 0.05 and 0.1 microM). CONCLUSIONS: Our
      preliminary results suggest that there may be a beneficial outcome in
      incorporating Taxol into the chemotherapeutic modalities of HNSCC patients in
      Taiwan. Furthermore, at least some of the OSCC cells may be more sensitive to
      Taxol/cisplatin than to Taxol/carboplatin or Taxol/5-FU treatment.

PMID- 15466822
TI  - Phase I trial of carboplatin and weekly paclitaxel in patients with advanced non
      small-cell lung cancer.
AB  - OBJECTIVE: This study was designed to determine the maximum tolerated dose of
      paclitaxel administered weekly in combination with carboplatin and to assess its
      dose limiting toxicity and preliminary activity in patients with previously
      untreated, advanced non-small-cell lung cancer. METHODS: Carboplatin was
      administered at a fixed dose that maintained an area under the curve of 6.
      Paclitaxel was given over 1 h once a week for 3 weeks starting at 60 mg/m(2) and
      escalated in 10 mg/m(2) increments. RESULTS: Twenty-one patients were treated
      with six dose levels (60, 70, 80, 90, 100, 110 mg/m(2)) of paclitaxel. The dose
      limiting toxicity was infection and the maximum tolerated dose was 110 mg/m(2).
      Nine of 21 (42.9%) patients demonstrated a therapeutic response. CONCLUSION:
      Weekly paclitaxel and carboplatin were well tolerated. Based on our results, 100
      mg/m(2) of paclitaxel for 3 weeks of a 4-week cycle, in combination with
      carboplatin, was recommended for a phase II study.

PMID- 15466823
TI  - Primary pulmonary non-Hodgkin's lymphoma.
AB  - BACKGROUND: Primary pulmonary non-Hodgkin's lymphoma is a very rare neoplasm. It
      is represented most commonly by marginal zone B-cell lymphoma of mucosa
      associated lymphoid tissue (MALT) type. Although there have been a few reviews of
      this lymphoma, clinical features, diagnostic procedure, optimal management and
      prognostic factors have not been well defined. METHODS: We reviewed the medical
      records of 24 patients who were pathologically and clinically diagnosed as
      primary pulmonary lymphoma between September 1995 and June 2003. RESULTS: There
      were 13 patients with MALT lymphoma and two with MALT lymphoma accompanied by
      large B-cell lymphoma, seven with diffuse large B-cell lymphoma and two with
      anaplastic large cell lymphoma. Half the patients were asymptomatic at
      presentation; 46% had respiratory symptoms and 16.7% had B-symptoms. Initial
      radiological findings were variable including nodules, masses, infiltrates or
      consolidation. The majority of patients (66.7%) needed surgical approaches (open
      thoracotomy or video-assisted thoracoscopy) for definite diagnosis. Bronchoscopy
      was performed in 83%, but only 30% showed a diagnostic yield. The 13 patients
      with MALT lymphoma were treated with a variety of modalities such as observation,
      surgery and single or combination chemotherapy, and combination chemotherapy was
      administered to 11 patients with non-MALT lymphoma regardless of surgery. The
      overall survival rate at 3 years for all 24 patients was 86% with a median follow
      up of 32 months. CONCLUSION: Although this entity of lymphoma appears to have a
      good prognosis, further clinical experience and long-term follow-up are needed to
      identify prognostic factors.

PMID- 15466824
TI  - Comparison of intraductal spread on dynamic contrast-enhanced MRI with
      clinicopathologic features in breast cancer.
AB  - OBJECTIVE: Contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a
      new diagnostic technology in various breast cancer treatments. However, little is
      known about the correlation between intraductal spread on CE-MRI and
      clinicopathologic features. This study was designed to evaluate these
      correlations for the surgical planning of breast cancer. METHODS: Twenty-six
      breast cancer lesions (in 26 female patients) treated by breast conserving
      surgery between March 2001 and March 2003 were evaluated retrospectively. CE-MRI
      was performed with a 1.5 T unit using a dedicated bilateral breast coil. RESULTS:
      In detecting intraductal spread of breast cancer, the sensitivity, specificity
      and accuracy of CE-MRI were 82.4%, 60.0% and 77.3%, respectively. On mammography
      (MMG), these were 21.1%, 100.0% and 42.3%, respectively. Therefore, CE-MRI has a
      higher sensitivity and accuracy, although with a lower specificity than MMG.
      Compared with breast cancer lesions without intraductal spread on CE-MRI, lesions
      with intraductal spread on CE-MRI were found more frequently in larger-sized
      tumors (P = 0.0088). CONCLUSION: Preoperative evaluation for intraductal spread
      by CE-MRI should be more useful than by MMG for breast cancer. When making the
      surgical decision regarding excision range, particular attention should be paid
      to this consideration for patients with larger-sized cancer tumors.

PMID- 15466825
TI  - Axillary sentinel node and tumour-related factors associated with non-sentinel
      node involvement in breast cancer.
AB  - BACKGROUND: After completion of axillary dissection, many breast cancer patients
      with axillary sentinel nodal involvement are found to have regional disease
      limited to the sentinel nodes. These patients are exposed to the morbidity of
      axillary clearance without any expected therapeutic benefit. METHODS: Sentinel
      node biopsy was performed either with Patent blue dye or with a combined dye,
      radiocolloid and gamma-probe-guided method involving peritumoral tracer
      administration. For a series of 150 consecutive patients with involved axillary
      sentinel nodes and axillary dissection, factors associated with non-sentinel
      nodal involvement were analysed in a multivariate analysis based on logistic
      regression with the use of fractional polynomials. RESULTS: The following
      variables were found to be potentially associated with non-sentinel node
      metastases: tumour size, sentinel node metastasis size, number of examined
      sentinel nodes, percentage of involved sentinel nodes (the latter two were found
      to be significant only when in combination), and extracapsular perinodal spread.
      CONCLUSIONS: Isolated tumour cells and micrometastases in axillary sentinel nodes
      carry a low risk of non-sentinel node metastasis. The risk of metastasis to
      further echelon nodes is higher with macrometastases, especially if there is
      extracapsular growth and the proportion of involved sentinel nodes is high.

PMID- 15466826
TI  - Detection of disseminated cancer cells in linitis plastica-type gastric
      carcinoma.
AB  - BACKGROUND: Dissemination of cancer cells in the abdominal cavity may lead to
      peritoneal carcinomatosis, a common event in the linitis plastica type of gastric
      carcinoma. Reverse transcriptase polymerase chain reaction (RT-PCR) is a
      sensitive technique for detecting these cells. METHODS: Peritoneal washings were
      obtained during laparotomy from 47 consecutive linitis plastica patients who
      preoperatively were considered candidates for curative resection. Together with
      conventional cytological examination using Papanicolaou staining, real-time RT
      PCR was performed to quantitate prospectively carcinoembryonic antigen (CEA) mRNA
      in these washings. Samples above a cutoff value for CEA mRNA were considered
      positive for molecular detection of disseminated cancer cells. RESULTS:
      Conventional cytological examination was positive in 43% (20/47). Positivity of
      CEA mRNA was much higher at 83% (39/47) and peritoneal carcinomatosis actually
      was observed in 77% (36/47), either at laparotomy or during postoperative follow
      up. Although only two of eight patients who were negative for CEA mRNA suffered
      from peritoneal carcinomatosis, three more patients died of recurrences through
      other metastatic pathways. Multivariate analysis revealed that curability of the
      operation (knowledge of the CEA mRNA values excluded) and T categories were the
      only significant independent prognostic factors. CONCLUSIONS: RT-PCR of the
      peritoneal washes had little value as a prognostic factor, but identified over
      80% of the patients planned for curative surgery to have disseminated cancer
      cells in the peritoneal cavity. Almost the same proportion of patients actually
      suffered from peritoneal carcinomatosis. These facts indicate why treatment with
      surgery alone rarely cures patients with linitis plastica.

PMID- 15466827
TI  - Three-dimensional conformal radiation therapy for unresectable hepatocellular
      carcinoma patients who had failed with or were unsuited for transcatheter
      arterial chemoembolization.
AB  - BACKGROUND: The purpose of our study was to evaluate the outcome of unresectable
      hepatocellular carcinoma (HCC) patients, who had either failed with or were
      unsuited for transcatheter arterial chemoembolization (TACE), treated with three
      dimensional conformal radiation therapy (3DCRT) and to determine the prognostic
      outcome factors. METHODS: From September 1999 to March 2003, 44 patients with
      unresectable HCC underwent 3DCRT. Thirty-seven patients were male and seven
      female. Mean age was 62 years, ranging from 34 to 88. Eastern Cooperative
      Oncology Group (ECOG) performance status was 0 in 10 patients, 1 in 19 patients,
      and 2 in 15 patients. According to Child-Pugh classification for cirrhosis of the
      liver, 32 patients were in class A and 12 patients in class B. There were 14
      patients with main portal vein thrombosis. Twenty patients had alpha-fetoprotein
      (AFP) level >400 ng/ml. Tumor size was <5 cm in 16 patients, 5-10 cm in 16
      patients, and >10 cm in 12 patients. Thirty-two patients had tumors of confluent
      type, the remaining patients presented a single hepatic tumor. Serum hepatitis
      antigen markers were positive for type B in 35 patients and type C in nine
      patients. Twenty-one patients had Okuda Stage I, 22 patients Stage II, and one
      patient Stage III. According to the AJCC staging system (5th edition), eight
      patients were in Stage II (T2N0M0), 19 in Stage IIIA (T3N0M0) and 17 in Stage IVA
      (T4N0M0). RESULTS: An objective response was observed in 27 of 44 patients,
      giving a response rate of 61.4%. The survival rates at 1, 2 and 3 years were
      60.5%, 40.3% and 32.0%, respectively. In the analysis of prognostic factors,
      Okuda stage, AJCC stage, portal vein thrombosis, pretreatment AFP level, and
      total dose of radiotherapy all had significant impact on survival. CONCLUSIONS:
      3DCRT induced a substantial tumor response rate of 61.4% with survival rates at
      1, 2 and 3 years of 60.5%, 40.3% and 32.0%, respectively, and a median survival
      time of 15.2 months in patients with unresectable HCC who had either failed with
      or were unsuited for TACE. The complications are acceptable and can be managed
      with conservative treatment. Although we do not know whether there is a survival
      benefit through the use of this treatment, 3DCRT seems to be a practical method
      of salvage for this subset of patients. Further study is warranted to evaluate
      the survival of such patients with and without this treatment.

PMID- 15466828
TI  - Cisplatin, paclitaxel and escalating doses of doxorubicin (TAP) in advanced
      ovarian cancer: a phase I trial.
AB  - BACKGROUND: The objectives of this phase I trial were to determine the maximum
      tolerated dose (MTD) and the recommended dose (RD) for phase II/III trials of
      doxorubicin (DOX) combined with paclitaxel (PTX) and cisplatin (CDDP) in patients
      with advanced ovarian cancer (AOC). METHODS: Twenty-eight patients with stage
      III/IV AOC received fixed doses of PTX (110 mg/m(2) over 24 h on day 1) and CDDP
      (75 mg/m(2) on day 2) and an escalating dose of DOX (20, 30, 40 or 50 mg/m(2) on
      day 1) every 3 weeks. The patients received up to six cycles of chemotherapy. At
      level 1, one of the original dose-limiting toxicities (DLTs), grade (G) 4
      neutropenia lasting for 4 days or longer, occurred in four of six patients. The
      criterion for DLT was amended to 'G4 neutropenia lasting for 8 days or longer
      accompanied with G4 leukopenia' and four additional patients were evaluated at
      level 1. RESULTS: According to the new criteria, DLT was observed only in one of
      nine patients except one ineligible patient at level 1 and two of six patients at
      level 4. G4 neutropenia and G4 leukopenia occurred in 85% and 44%, respectively,
      in the first course of chemotherapy. Non-hematological toxicity was generally
      mild or moderate. MTD was not determined at the planned dose levels. A clinical
      response was observed in 16 of 19 (84%) evaluable patients. Further dose
      escalation was not performed and RD was determined as level 4 because more than
      30% of cycles required some modification of chemotherapy at level 4. CONCLUSION:
      The combination of TAP including 50 mg/m(2) of DOX is feasible and well tolerated
      as first line chemotherapy in AOC, warranting further study of this regimen.

PMID- 15466829
TI  - Gemcitabine and cisplatin combination chemotherapy in intrahepatic
      cholangiocarcinoma as second-line treatment: report of four cases.
AB  - BACKGROUND: Intrahepatic cholangiocarcinoma is a chemoresistant cancer for which
      effective chemotherapy is not yet available. We investigated the efficacy and
      toxicity of the combination of gemcitabine and cisplatin as second-line
      chemotherapy in four patients with advanced, progressive intrahepatic
      cholangiocarcinoma. METHODS: Four patients were enrolled who had previous
      chemotherapy with epirubicin, cisplatin and protracted infusion of 5-FU. All
      these patients treated with gemcitabine 1000 mg/m(2) intravenously (i.v.) on days
      1 and 8 for 30 min, cisplatin 75 mg/m(2) i.v. on day 1 for 90 min, given every 21
      days. RESULTS: Two patients had partial response (PR), and two had stable disease
      (SD), with one of the latter showing a decrease in tumor size of 35%. Median time
      to progression was 5 months (range, 3-9 months) and median survival was 9 months
      (range, 8-16 months). Toxicity was mild and tolerable. CONCLUSIONS: Gemcitabine
      and cisplatin combination chemotherapy may be an effective regimen for advanced
      intrahepatic cholangiocarcinoma. Further study is warranted to determine the
      efficacy of this combination regimen.

PMID- 15466830
TI  - Aggressive multimodal treatment for peritoneal dissemination and needle tract
      implantation of hepatocellular carcinoma: a case report.
AB  - We encountered a patient with hepatocellular carcinoma (HCC) with peritoneal
      dissemination and needle tract implantation, both of which were strongly
      suspected to have been caused by percutaneous needle biopsy. The patient was a 65
      year-old man. Partial hepatectomy of subsegment VI had been performed following
      the diagnosis of HCC by percutaneous needle biopsy in February 1997. After this
      first surgery, the patient additionally underwent five further surgeries for the
      treatment of intrahepatic recurrences, peritoneal recurrences and needle tract
      implantation caused by the percutaneous needle biopsy. The intrahepatic and
      peritoneal recurrences were surgically controlled for 3 years after the fifth
      operation. The needle tract implantation was first resected in February 2001.
      Since then, treatment by surgery and radiotherapy has been administered twice for
      local recurrences forming tumor thrombosis of the abdominal wall. Now, 7 years
      after the first surgery, the patient remains alive without any evidence of
      recurrence. This case report serves to emphasize that needle tract implantation
      and peritoneal seeding caused by percutaneous needle biopsy are rare but possible
      complications. When such iatrogenic spreading of malignant cells occurs,
      aggressive multimodal treatment is well worth considering. Wide resection of the
      tumor including the adjacent soft tissues should be performed in these cases,
      considering that the tumor spreads along the subcutaneous veins in needle tract
      implantation of HCC and repeated aggressive surgeries could provide good local
      control.

PMID- 15466831
TI  - The novel germline mutation of the hMLH1 gene in a case of suspected hereditary
      non-polyposis colorectal cancer (HNPCC) in a patient with no family history of
      cancer.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is a very important clinical
      entity in oncology. In order to identify HNPCC, the international diagnostic
      criteria, named 'Amsterdam criteria', has been used. In this report, we present a
      patient with HNPCC who completely lacks a family history of cancer, thus does not
      meet the revised Amsterdam criteria and was finally confirmed as HNPCC by genetic
      testing which revealed a novel germline mutation of the hMLH1 gene. The proband
      was a 52-year-old Japanese female with a diagnosis of advanced ascending colon
      cancer. She had a past history of Miles' operation for rectal cancer at the age
      of 40. A subtotal colectomy was performed and the subsequent microsatellite
      instability (MSI) analysis revealed high MSI in the resected tumor tissue.
      PCR/direct sequencing analysis of the genomic DNA revealed the base deletion
      2006delAAAAG at codon 669 in exon 18 of the hMLH1 gene, which was considered to
      be a pathogenic mutation. According to the Human Mutation Database and
      International Collaborative Group on HNPCC (ICG-HNPCC) Database, this is the
      first report of this type of deletion mutation in the hMLH1 gene.

PMID- 15466832
TI  - Cancer statistics digest. Mortality trend of prostate, breast, uterus, ovary,
      bladder and "kidney and other urinary tract" cancer in Japan by birth cohort.

PMID- 15466836
TI  - Trauma exposure and posttraumatic stress disorder: a study of youths in urban
      America.
AB  - We estimate the cumulative occurrence of traumatic events and posttraumatic
      stress disorder (PTSD), using Diagnostic and Statistical Manual of Mental
      Disorders, fourth edition (DSM-IV) criteria, in a high-risk sample of young
      people in urban United States. The epidemiological sample (n = 2,311) was
      recruited in 1985-1986 at entry into first grade of a public school system of a
      large mid-Atlantic city. Participants were interviewed about history of trauma
      and PTSD in 2000-2002 when their mean age was 21 years (n = 1,698). We found that
      the lifetime occurrence of assaultive violence was 62.6% in males and 33.7% in
      females. The risk of assaultive violence in males (but not females) varied by
      childhood area of residence within the city; the occurrence of other traumas did
      not vary by area of childhood residence. Females had a higher risk of PTSD than
      males following assaultive violence (odds ratio = 4.0, 95% confidence interval
      2.0-8.3), but not following other traumas. A comparison of the results from this
      largely inner-city sample with the results from a recent study of a largely
      suburban sample in another region of the United States in which the same criteria
      and measures of trauma and PTSD were used suggested the possibility that males'
      risk for assaultive violence and females' risk for PTSD following exposure to
      assaultive violence might vary by characteristics of the social environment.

PMID- 15466837
TI  - Child pedestrians: the role of parental beliefs and practices in promoting safe
      walking in urban neighborhoods.
AB  - The purpose of this study was to describe parents' child pedestrian safety
      practices, knowledge, risk perceptions, and beliefs. We surveyed 732 parents from
      four elementary schools in urban neighborhoods that differed in income, and child
      pedestrian injury risks. Findings indicated that most parents taught their
      children street safety. Few (16%) knew basic pedestrian safety facts; 46%
      believed children younger than 10 years could safely cross streets alone; 50%
      believed a child pedestrian crash was likely. Parents in lower income
      neighborhoods reported the highest rates of unpleasant walking environments and
      concerns about drug dealers, crime, violence, and trash. We conclude that
      education should focus on children's risk, developmental capabilities, and
      supervision needs. Promoting physical activity in urban neighborhoods, especially
      lower income ones, must address concerns about the physical and social
      environment.

PMID- 15466838
TI  - Narrowing the income gaps in preventive care for young children: families in
      healthy steps.
AB  - Persistent unmet preventive and developmental health care needs of children in
      low-income families are a national concern. Recently, there have been efforts to
      promote developmental services as part of primary care for all young children.
      However, there is limited research to determine whether the neediest families are
      well in universal interventions. In our study, we assessed if disparities persist
      in utilization of developmental services, well child care, and satisfaction with
      care among low-, middle-, and high-income families participating in Healthy Steps
      for Young Children. Healthy Steps is a national experiment that incorporated
      developmental services into primary care for children from birth to 3 years of
      age. In the United States, 15 pediatric practices participated in this
      prospective study. At birth, 2,963 children were enrolled between September 1996
      and November 1998 and followed through 33 months of age. The utilization of
      developmental services, satisfaction with care, and receipt of age-appropriate
      well child visits were measured at 30-33 months and adjusted for demographic and
      economic covariates. We found that the adjusted odds of low-income families did
      not differ from high-income families in receipt of four or more Healthy Steps
      services, a home visit, or discussing five or more child rearing topics. Low- and
      middle-income families had reduced adjusted odds of receiving a developmental
      assessment and books to read. The adjusted odds of low- and middle-income
      families did not differ from high-income families in being very satisfied with
      care provided or receiving age-appropriate well child visits. A universal
      practice-based intervention such as Healthy Steps has the potential to reduce
      income disparities in the utilization of preventive services, timely well child
      care, and satisfaction with care.

PMID- 15466839
TI  - The impact of insurance lapse among low-income children.
AB  - Children living in poverty not only have disproportionately more health problems,
      but also have disproportionately lower health care service utilization. Change,
      whether in health care delivery system or in family living situation, may
      interfere with or jeopardize insurance status and thereby influence access to
      health care services. We hypothesized that children who have maintained Medicaid
      insurance compared to those who have not will be more likely to have preventive
      care visits and less likely to have emergency room visits. We further
      hypothesized that transient situations such as homeless episodes, foster care
      placement, and living in more than one location in the same 1-year period will
      contribute to loss in Medicaid coverage. This retrospective cohort study was
      conducted at an urban children's hospital outpatient clinic at which 210 family
      respondents were recruited over a 1-year period. An in-person interview
      containing several standardized instruments was administered to the caregiver. In
      addition, children's medical records were retrospectively abstracted from point
      of study entry to first contact. Findings indicated that children who lost
      Medicaid coverage, compared to others, had significantly fewer preventive care
      health visits. There were no differences in emergency room visits. Transient
      situations did not appear to influence preventive or emergency room care. In
      addition, the change into a managed-care delivery system also increased loss of
      coverage. Loss of coverage may be a barrier to preventive care services. To
      ensure optimal preventive care services, the onus is on the providers and plans
      to facilitate continued insurance coverage.

PMID- 15466840
TI  - Predictors of initiation into prostitution among female street youths.
AB  - Prostitution among female street youths represents an important risk factor for
      several health problems. Little is known about the incidence and determinants of
      prostitution in this vulnerable population, and no data have been previously
      reported based on a longitudinal follow-up study. The objective of this study was
      to determine predictors of initiation into prostitution among female street
      youths. Female youths aged 14 to 25 years were enrolled in the Montreal Street
      Youth Cohort. They completed a baseline and at least one follow-up questionnaire
      between January 1995 and March 2000. Girls who reported never having engaged in
      prostitution at baseline were followed prospectively to estimate the incidence
      and predictors of prostitution. Of the 330 female street youths enrolled as of
      September 2000 in the cohort, 148 reported no history of involvement in
      prostitution at baseline and completed at least one follow-up questionnaire. Of
      these 148 girls, 33 became involved in prostitution over the course of the study
      (mean follow-up 2.4 years), resulting in an incidence rate of 11.1/100 person
      years. Multivariate Cox regression analysis revealed having a female sex partner
      (adjusted hazard ratio [AHR] 3.8; 95% confidence interval [CI] 1.6-9.1) was an
      independent predictor of initiation into prostitution after controlling for
      having been on the street at age 15 years or younger (AHR 1.8, 95% CI 0.9-3.8),
      using acid or phencyclidine (PCP; AHR 2.0, 95% CI 0.9-4.6), using heroin (AHR
      1.9, 95% CI 0.7-5.5), the use of drugs greater than twice per week (AHR 1.9, 95%
      CI 0.9-4.2), and injection drug use (AHR 0.8, 95% CI 0.3-2.4). The incidence of
      prostitution in female street youths was elevated. Having a female sex partner
      was a strong predictor of initiating involvement in prostitution.

PMID- 15466841
TI  - Homeless people's trust and interactions with police and paramedics.
AB  - Although the health impact of patients' trust in physicians has been well
      documented, less is known about the possible health effects of trust in police or
      paramedics. Homeless people frequently interact with police officers and
      paramedics, and these experiences may affect their health and future willingness
      to seek emergency assistance. We examined homeless people's self-reported
      interactions with police and paramedics in Toronto, Canada, and their level of
      trust in these emergency service providers. In a sample of 160 shelter users, 61%
      had interacted with police in the last 12 months, and 37% had interacted with
      paramedics (P = .0001). The proportion of subjects who expressed willingness to
      call police in an emergency was significantly lower than those willing to call
      paramedics in an emergency (69% vs. 92%, P = .0001). On a Likert scale ranging
      from a minimum of 0 to a maximum of 5, trust levels were lower in police than in
      paramedics (median level 3 vs. 5, P = .0001). Among shelter users, 9% (95%
      confidence interval [CI], 5% to 14%) reported an assault by a police officer in
      the last year, and 0% (95% CI, 0% to 4%) reported an assault by a paramedic.
      These findings showed that homeless people have much lower levels of trust in
      police than paramedics. Reports of negative interactions with police are not
      uncommon, and homeless people's perceptions of the police may pose a barrier to
      seeking emergency assistance. Further research is needed for objective
      characterization of homeless people's interactions with police officers and the
      potential health implications of low levels of trust in the police.

PMID- 15466842
TI  - Substance-abusing urban homeless in the late 1990s: how do they differ from non
      substance-abusing homeless persons?
AB  - Much of our understanding of substance abuse and homelessness comes from data
      from the 1980s and may not necessarily reflect issues or trends prevalent during
      the 1990s. We report data from a two-city, community-based, populations
      proportionate sample of 531 randomly selected homeless adults; the study was
      conducted in 1997 and compared substance-abusing to non-substance-abusing
      respondents. Most (78.3%) met criteria for substance abuse/dependence and were
      abusing either cocaine or alcohol and cocaine (68.5%). In the multiple logistic
      regression model, male gender (odds ratio [OR] 2.94, 95% confidence interval [CI]
      1.70-5.09), less than a 12th grade education (OR 1.96, 95% CI 1.11-3.46),
      hustling or stealing for sustenance (OR 3.14, 95% CI 1.15-8.55), and identifying
      a need to learn how to manage one's money (OR 2.41, 95% CI 1.45-3.98) were
      independently associated with substance abuse/dependence. Drug abuse/dependence
      and polysubstance use among urban homeless persons became a more prevalent issue
      in the late 1990s. These individuals have unique needs that will require tailored
      interventions.

PMID- 15466843
TI  - Homelessness and HIV risk behaviors among injection drug users.
AB  - This article uses data from an 8-year study of injection drug users to examine
      whether homelessness independently influenced the likelihood of engaging in human
      immunodeficiency virus (HIV) risk behaviors. Fixed effects regression analyses
      are used to estimate the associations between four different housing contexts and
      four different behaviors related to transmitting HIV infections. Results showed
      that 16% of the study group experienced homelessness at some point during the
      study, and that homelessness was significantly associated with a higher
      likelihood of frequenting shooting galleries (odds ratio = 2.05), but did not
      have a significant effect on sharing syringes, sharing other injection drug
      paraphernalia, or participating in paid sex. These results provide limited
      support for positing homelessness as independently associated with increased
      levels of HIV-related risk behavior among injection drug users and highlights the
      need for more research that examines the housing dynamics among this population.

PMID- 15466844
TI  - Jail incarceration and birth outcomes.
AB  - This study examined the relationships between jail incarceration during pregnancy
      and infant birth weight, preterm birth, and fetal growth restriction. We used
      multivariate regression analyses to compare outcomes for 496 births to women who
      were in jail for part of pregnancy with 4,960 Medicaid-funded births as matched
      community controls. After adjusting for potential confounding variables, the
      relationship between jail incarceration and birth outcomes was modified by
      maternal age. Relative to controls, women incarcerated during pregnancy had
      progressively higher odds of low birth weight and preterm birth through age 39
      years; conversely, jail detainees older than 39 years were less likely than
      controls to experience low birth weight or preterm birth. For women in jail at
      all ages, postrelease maternity case management was associated with decreased
      odds of low birth weight, whereas prenatal care was associated with decreased
      odds of preterm birth. Local jails are important sites for public health
      intervention. Efforts to ensure that all pregnant women released from jail have
      access to enhanced prenatal health services may improve perinatal outcomes for
      this group of particularly vulnerable women and infants.

PMID- 15466845
TI  - Jail management of arrestees/inmates enrolled in community methadone maintenance
      programs.
AB  - Anecdotal evidence suggests that many jails fail to adequately detoxify
      arrestees/inmates who are enrolled in methadone programs, but there are few
      empirical data. The objective of this study was to assess how jails manage
      arrestees/inmates enrolled in methadone programs. A national survey of 500 jails
      in the United States was conducted. Surveys were mailed to the 200 largest jails
      in the country in addition to a random sample of 300 of the remaining jails (10%
      sample). Jails were specifically asked about management of opiate dependency
      among arrestees/inmates enrolled in methadone programs. Weighted logistic
      regression analyses were conducted to assess predictors of continuing methadone
      during incarceration and use of recommended detoxification protocols. Among the
      245 (49%) jails that responded, only 1 in 4 (27%) reported they contacted the
      methadone programs regarding dose, and only 1 in 8 (12%) continued methadone
      during the incarceration. Very few (2%) jails used methadone or other opiates for
      detoxification. Most used clonidine. However, half (48%) of jails failed to use
      clonidine, methadone, or other opiates to detoxify inmates from methadone.
      Weighted logistic regression models showed that moderately large jails and those
      located in the South and Midwest were significantly more likely to continue
      methadone. Very large jails, those with an estimated prevalence of opiate
      dependence of 6%-10% among arrestees/inmates, and those located in the Northeast
      were significantly more likely to use recommended detoxification protocols. Very
      few jails provided continuous treatment to arrested persons on methadone, and
      half failed to detoxify arrestees/inmates using recommended protocols. These
      practices jeopardize the health and well-being of persons enrolled in methadone
      programs and underscore the need for uniform national policies within jails.

PMID- 15466846
TI  - The cost of inaction on HIV transmission among injection drug users and the
      potential for effective interventions.
AB  - Estimated and potential medical costs of treating patients infected with human
      immunodeficiency virus (HIV) in urban areas of high HIV prevalence have not been
      well defined. We estimated the total medical cost of HIV disease among injection
      drug users in Vancouver, British Columbia, Canada, assuming stable and increasing
      HIV prevalence. Total medical costs were estimated by multiplying the average
      lifetime medical cost per person by the number of HIV-infected individuals. We
      assumed the cost of each HIV infection to be 150,000 Canadian dollars, based on
      empirical data, and HIV prevalence estimates were derived from the Vancouver
      Injection Drug Users Study (VIDUS) and external data sources. By use of Monte
      Carlo simulation methodology, we performed sensitivity analyses to estimate total
      medical cost, assuming the HIV prevalence remained stable at 31% and under a
      scenario in which the prevalence rose to 50%. Expected medical expenditures based
      on current HIV prevalence levels were estimated as 215,852,613 Canadian dollars.
      If prevalence rises to 50% as reported in other urban centers, the median
      estimated medical cost would be approximately 348,935,865 Canadian dollars. This
      represents a difference in the total costs between the two scenarios of
      133,083,253 Canadian dollars. Health planners should consider that predicted
      medical expenditures related to the HIV epidemic among injection drug users in
      our setting may cost an estimated 215,852,613 Canadian dollars. If funding cannot
      be found for appropriate prevention interventions and the prevalence rises to
      50%, a further 133,083,253 Canadian dollars may be required.

PMID- 15466847
TI  - A multistate trial of pharmacy syringe purchase.
AB  - Pharmacies are a potential site for access to sterile syringes as a means for
      preventing human immunodeficiency virus (HIV), but the type and extent of their
      utility is uncertain. To examine pharmacy syringe purchase, we conducted a
      standardized, multistate study in urban and rural areas of four states in which
      attempts to purchase syringes were documented. Of 1,600 overall purchase
      attempts, 35% were refused. Colorado (25%) and Connecticut (28%) had
      significantly lower rates of refusal than Kentucky (41%) and Missouri (47%).
      Furthermore, urban settings had higher rates of refusal (40%) than rural settings
      (31%, P < .01). Race and gender did not have a consistent impact on rates of
      refusal. Despite potential advantages of pharmacies as sites for access to
      sterile syringes, pharmacy purchase of syringes faces significant obstacles in
      terms of the practices in different jurisdictions.

PMID- 15466848
TI  - Perceptions of neighborhood environment for physical activity: is it "who you
      are" or "where you live"?
AB  - Lack of physical activity among American adults is a serious public health
      concern. Many factors influence activity levels, and most research has focused on
      either individual factors, such as race and income, or on characteristics of the
      physical environment, such as the availability of parks. Our study used a cross
      sectional multilevel design to examine the influences of individual- and
      neighborhood-level characteristics on participant's perceptions of their
      neighborhood as an appropriate venue for physical activity. Study participants
      were 1,073 African American and white adults living in the St. Louis, Missouri,
      metropolitan area. Individual-level information was gathered from self
      administered questionnaires; neighborhood-level data for these same individuals
      were obtained from the 2000 US Census. We found that both individual and
      neighborhood characteristics were significant predictors of how individuals
      perceived physical activity opportunities in their neighborhood, and that African
      Americans perceived their neighborhoods as less safe and less pleasant for
      physical activity than did whites, regardless of the racial composition of the
      neighborhood. We suggest that any evaluation of opportunities for physical
      activity within a neighborhood should include consideration of resident's
      perceptions of the safety and pleasantness of using them, and that the role of
      perceived and actual neighborhood conditions in explaining disparities in
      physical activity between African American and other populations should be
      examined further.

PMID- 15466849
TI  - Reliability of self-reported neighborhood characteristics.
AB  - The majority of studies examining the relation between neighborhood environments
      and health have used census-based indicators to characterize neighborhoods. These
      studies have shown that neighborhood socioeconomic characteristics are associated
      with a range of health outcomes. Establishing if these associations reflect
      causal relations requires testing hypotheses regarding how specific features of
      neighborhoods are related to specific health outcomes. However, there is little
      information on the reliability of neighborhood measures. The purpose of this
      study was to estimate the reliability of a questionnaire measuring various self
      reported measures of the neighborhood environment of possible relevance to
      cardiovascular disease. The study consisted of a face-to-face and telephone
      interview administered twice to 48 participants over a 2-week period. The face-to
      face and telephone portions of the interview lasted an average of 5 and 11
      minutes, respectively. The questionnaire was piloted among a largely Latino and
      African American study sample recruited from a public hospital setting in New
      York City. Scales were used to assess six neighborhood domains: aesthetic
      quality, walking/exercise environment, safety from crime, violence, access to
      healthy foods, and social cohesion. Cronbach's alpha's ranged from .77 to .94 for
      the scales corresponding to these domains, with test-retest correlations ranging
      from 0.78 to 0.91. In addition, neighborhood indices for presence of recreational
      facilities, quality of recreational facilities, neighborhood participation, and
      neighborhood problems were examined. Test-retest reliability measures for these
      indices ranged from 0.73 to 0.91. The results from this study suggested that self
      reported neighborhood characteristics can be reliably measured.

PMID- 15466850
TI  - Homicide risk across race and class: a small-area analysis in Massachusetts and
      Rhode Island.
AB  - Areas with higher absolute poverty and higher income inequality have been
      associated with higher risk of homicide victimization. In addition, studies of
      differential homicide rates have indicated that black persons are at a higher
      risk of homicide compared to white persons. However, few studies directly
      compared risk of homicide offending or victimization between Hispanic persons and
      non-Hispanic white persons, and few studies have attempted to examine the
      interaction between race and residential neighborhood socioeconomic measures on
      homicide risk. This population-based retrospective study comprised all white,
      black, and Hispanic 15- to 44-year-old men included in the 1990 US Census as
      Rhode Island or Massachusetts residents. Vital statistics registries were linked
      to 1990 US Census data to provide information on small-area characteristics.
      Overall, we observed a trend of increasing homicide risk as block-group
      socioeconomic position descended. The data indicated that block-group poverty,
      female-headed households, home ownership, and higher education were all strongly
      associated with homicide risk after stratifying by race and age of victim and
      adjusting for other block-group socioeconomic characteristics. Race was a strong
      modifier for absolute risk difference for the relation between risk of homicide
      and socioeconomic surroundings. Our analyses suggested that area-based
      interventions that would improve neighborhood social and economic conditions
      would be effective in decreasing risk of homicide for men.

PMID- 15466852
TI  - Regulation of 2-oxoglutarate (alpha-ketoglutarate) dehydrogenase stability by the
      RING finger ubiquitin ligase Siah.
AB  - The 2-oxoglutarate dehydrogenase complex (OGHDC) (also known as the alpha
      ketoglutarate dehydrogenase complex) is a rate-limiting enzyme in the
      mitochondrial Krebs cycle. Here we report that the RING finger ubiquitin-protein
      isopeptide ligase Siah2 binds to and targets OGDHC-E2 for ubiquitination
      dependent degradation. OGDHC-E2 expression and activity are elevated in Siah2(-/
      ) cells compared with Siah2(+)(/)(+) cells. Deletion of the mitochondrial
      targeting sequence of OGDHC-E2 results in its cytoplasmic localization and rapid
      proteasome-dependent degradation in Siah2(+)(/)(+) but not in Siah2(-/-) cells.
      Significantly, because of its overexpression or disruption of the mitochondrial
      membrane potential, the release of OGDHC-E2 from mitochondria to the cytoplasm
      also results in its concomitant degradation. The role of the Siah family of
      ligases in the regulation of OGDHC-E2 stability is expected to take place under
      pathological conditions in which the levels of OGDHC-E2 are altered.

PMID- 15466851
TI  - Co-occurring Hepatitis C, substance use, and psychiatric illness: treatment
      issues and developing integrated models of care.
AB  - Hepatitis C virus (HCV) infection is transmitted by injection drug use and
      associated with psychiatric conditions. Patients with drug use or significant
      psychiatric illness have typically been excluded from HCV treatment trials noting
      the 1997 National Institutes of Health Consensus Statement on HCV that indicated
      active drug use and major depressive illness were contraindications to treatment
      of HCV infection. However, the 2002 NIH Consensus Statement recognized that these
      patients could be effectively treated for HCV infection and recommended that
      treatment be considered on a case-by-case basis. Treating HCV infection in these
      patients is challenging, with drug use relapse possibly leading to psychosocial
      instability, poor adherence, and HCV reinfection. Interferon therapy may
      exacerbate preexisting psychiatric symptoms. Co-occurring human immunodeficiency
      virus or hepatitis B virus provide additional challenges, and access to ancillary
      medical and psychiatric services may be limited. Patients with co-occurring HCV
      infection, substance use, and psychiatric illness can complete interferon
      treatment with careful monitoring and aggressive intervention. Clinicians must
      integrate early interventions for psychiatric conditions and drug use into their
      treatment algorithm. Few programs or treatment models are designed to manage co
      occurring substance use, psychiatric illness, and HCV infection and therapy. The
      National Institute on Drug Abuse convened a panel of experts to address the
      current status and the long-range needs through a 2-day workshop, Co-occurring
      Hepatitis C, Substance Abuse, and Psychiatric Illness: Addressing the Issues and
      Developing Integrated Models of Care. This conference report summarizes current
      data, medical management issues, and strategies discussed.

PMID- 15466853
TI  - Human P-selectin glycoprotein ligand-1 (PSGL-1) interacts with the skin
      associated chemokine CCL27 via sulfated tyrosines at the PSGL-1 amino terminus.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1), a sialomucin expressed on leukocytes,
      is a major ligand for P-selectin and mediates leukocyte rolling on the
      endothelium. Here we show that human PSGL-1 interacts with CCL27
      (CTACK/ILC/ESkine), a skin-associated chemokine that attracts skin-homing T
      lymphocytes. A recombinant soluble form of PSGL-1 (rPSGL-Ig) preferentially bound
      CCL27 among several chemokines tested. This interaction was abrogated by
      arylsulfatase treatment of rPSGL-Ig, suggesting that sulfated tyrosines play a
      critical role. In contrast, removal of either N-glycans or O-glycans by
      glycosidase treatment of rPSGL-Ig did not affect the interaction. The binding of
      CCL27 to a recombinant PSGL-1 synthesized in the presence of a sulfation
      inhibitor was lower than that produced in normal medium. Moreover, mutation of
      the tyrosines at the amino terminus of PSGL-1 to phenylalanine abolished the
      binding, further supporting the role of sulfated tyrosines in the CCL27-PSGL-1
      interaction. Functionally, rPSGL-Ig reduced the chemotaxis of L1.2 cells
      expressing CCR10, the receptor for CCL27. In addition, the expression of human
      PSGL-1 on CCR10-expressing L1.2 cells resulted in reduced chemotaxis to CCL27.
      These findings suggest a role for PSGL-1 in regulating chemokine-mediated
      responses, in addition to its role as a selectin ligand.

PMID- 15466854
TI  - Pea3 transcription factor cooperates with USF-1 in regulation of the murine bax
      transcription without binding to an Ets-binding site.
AB  - The Pea3 transcription factor (which belongs to the PEA3 group) from the Ets
      family has been shown to be involved in mammary embryogenesis and oncogenesis.
      However, except for proteinases, only few of its target genes have been reported.
      In the present report, we identified bax as a Pea3 up-regulated gene. We provide
      evidence of this regulation by using Pea3 overexpression and Pea3 silencing in a
      mammary cell line. Both Pea3 and Erm, another member of the PEA3 group, are able
      to transactivate bax promoter fragments. Although the minimal Pea3-regulated bax
      promoter does not contain an Ets-binding site, two functional upstream
      stimulatory factor-regulated E boxes are present. We further demonstrate the
      ability of Pea3 and USF-1 to cooperate for the transactivation of the bax
      promoter, mutation of the E boxes dramatically reducing the Pea3 transactivation
      potential. Although Pea3 did not directly bind to the minimal bax promoter, we
      provide evidence that USF-1 could form a ternary complex with Pea3 and DNA. Taken
      together, our results suggest that Pea3 may regulate bax transcription via the
      interaction with USF-1 but without binding to DNA.

PMID- 15466855
TI  - SV2B regulates synaptotagmin 1 by direct interaction.
AB  - SV2 proteins are abundant synaptic vesicle proteins expressed in two major (SV2A
      and SV2B) and one minor (SV2C) isoform. SV2A and SV2B have been shown to be
      involved in the regulation of synaptic vesicle exocytosis. Previous studies found
      that SV2A, but not SV2B, can interact with the cytoplasmic domain of
      synaptotagmin 1, a Ca2+ sensor for synaptic vesicle exocytosis. To determine
      whether SV2B can interact with full-length synaptotagmin 1, we performed
      immunoprecipitations from brain protein extracts and found that SV2B interacts
      strongly with synaptotagmin 1 in a detergent-resistant, Ca2+ -independent manner.
      In contrast, an interaction between native SV2A and synaptotagmin 1 was not
      detectable under these conditions. The SV2B-synaptotagmin 1 complex also
      contained the synaptic t-SNARE proteins, syntaxin 1 and SNAP-25, suggesting that
      SV2B may participate in exocytosis by modulating the interaction of synaptotagmin
      1 with t-SNARE proteins. Analysis of retinae in SV2B knock-out mice revealed a
      strong reduction in the level of synaptotagmin 1 in rod photoreceptor synapses,
      which are unique in that they express only the SV2B isoform. In contrast, other
      synaptic vesicle proteins were not affected by SV2B knock out, indicating a
      specific role for SV2B in the regulation of synaptotagmin 1 levels at certain
      synapses. These experiments suggest that the SV2B-synaptotagmin 1 complex is
      involved in the regulation of synaptotagmin 1 stability and/or trafficking. This
      study has demonstrated a new role of SV2B as a regulator of synaptotagmin 1 that
      is likely mediated by direct interaction of these two synaptic proteins.

PMID- 15466856
TI  - Ets-dependent regulation of target gene expression during megakaryopoiesis.
AB  - Megakaryopoiesis is the process by which hematopoietic stem cells in the bone
      marrow differentiate into mature megakaryocytes. The expression of megakaryocytic
      genes during megakaryopoiesis is controlled by specific transcription factors.
      Fli-1 and GATA-1 transcription factors are required for development of
      megakaryocytes and promoter analysis has defined in vitro functional binding
      sites for these factors in several megakaryocytic genes, including GPIIb, GPIX,
      and C-MPL. Herein, we utilize chromatin immunoprecipitation to examine the
      presence of Ets-1, Fli-1, and GATA-1 on these promoters in vivo. Fli-1 and Ets-1
      occupy the promoters of GPIIb, GPIX, and C-MPL genes in both Meg-01 and CMK11-5
      cells. Whereas GPIIb is expressed in both Meg-01 and CMK11-5 cells, GPIX and C
      MPL are only expressed in the more differentiated CMK11-5 cells. Thus, in vivo
      occupancy by an Ets factor is not sufficient to promote transcription of some
      megakaryocytic genes. GATA-1 and Fli-1 are both expressed in CMK11-5 cells and co
      occupy the GPIX and C-MPL promoters. Transcription of all three megakaryocytic
      genes is correlated with the presence of acetylated histone H3 and phosphorylated
      RNA polymerase II on their promoters. We also show that exogenous expression of
      GATA-1 in Meg-01 cells leads to the expression of endogenous c-mpl and gpIX mRNA.
      Whereas GPIIb, GPIX, and C-MPL are direct target genes for Fli-1, both Fli-1 and
      GATA-1 are required for formation of an active transcriptional complex on the C
      MPL and GPIX promoters in vivo. In contrast, GPIIb expression appears to be
      independent of GATA-1 in Meg-01 cells.

PMID- 15466857
TI  - Inhibition of NF-kappa B activation by peptides targeting NF-kappa B essential
      modulator (nemo) oligomerization.
AB  - NF-kappa B essential modulator/IKK-gamma (NEMO/IKK-gamma) plays a key role in the
      activation of the NF-kappa B pathway in response to proinflammatory stimuli.
      Previous studies suggested that the signal-dependent activation of the IKK
      complex involves the trimerization of NEMO. The minimal oligomerization domain of
      this protein consists of two coiled-coil subdomains named Coiled-coil 2 (CC2) and
      leucine zipper (LZ) (Agou, F., Traincard, F., Vinolo, E., Courtois, G., Yamaoka,
      S., Israel, A., and Veron, M. (2004) J. Biol. Chem. 279, 27861-27869). To search
      for drugs inhibiting NF-kappa B activation, we have rationally designed cell
      permeable peptides corresponding to the CC2 and LZ subdomains that mimic the
      contact areas between NEMO subunits. The peptides were tagged with the
      Antennapedia/Penetratin motif and delivered to cells prior to stimulation with
      lipopolysaccharide. Peptide transduction was monitored by fluorescence-activated
      cell sorter, and their effect on lipopolysaccharide-induced NF-kappa B activation
      was quantified using an NF-kappa B-dependent beta-galactosidase assay in stably
      transfected pre-B 70Z/3 lymphocytes. We show that the peptides corresponding to
      the LZ and CC2 subdomains inhibit NF-kappa B activation with an IC(50) in the mum
      range. Control peptides, including mutated CC2 and LZ peptides and a heterologous
      coiled-coil peptide, had no inhibitory effect. The designed peptides are able to
      induce cell death in human retinoblastoma Y79 cells exhibiting constitutive NF
      kappa B activity. Our results provide the "proof of concept" for a new and
      promising strategy for the inhibition of NF-kappa B pathway activation through
      targeting the oligomerization state of the NEMO protein.

PMID- 15466859
TI  - VP1 of foot-and-mouth disease virus induces apoptosis via the Akt signaling
      pathway.
AB  - Foot-and-mouth disease virus (FMDV) binds to cellular integrins through an RGD
      motif in its capsid protein, VP1. It is unclear, however, what kind of cellular
      event(s) are triggered after the binding of VP1 to the cells. In this study, we
      show that aqueous soluble recombinant DNA-derived VP1 (rVP1) of FMDV induced
      apoptosis of BHK-21 cells after binding to integrins. In addition, treatment of
      BHK-21 cells with rVP1 resulted in deactivation of Akt and enhancement of several
      proapoptotic responses such as dephosphorylation of glycogen synthase kinase
      3beta and cleavage of procaspase-3, -7, and -9. Additional studies revealed that
      the rVP1 treatment caused apoptosis of cancer cells, including MCF-7 (a breast
      carcinoma cell line with a functional deletion of the caspase-3 gene) and PC-3 (a
      sphingosine 1-phosphate receptor subtype 3-deficient androgen-independent
      prostate cancer cell line). These results suggest that rVP1 of FMDV may be used
      selectively as a potent apoptotic agent for human cancer by modulating the Akt
      signaling pathway and that its effect is not primarily dependent on either
      activation of procaspase-3 or deactivation of sphingosine 1-phosphate receptor
      subtype 3.

PMID- 15466858
TI  - 6-Phosphofructo-2-kinase (pfkfb3) gene promoter contains hypoxia-inducible factor
      1 binding sites necessary for transactivation in response to hypoxia.
AB  - The up-regulation of glycolysis to enhance the production of energy under reduced
      pO(2) is a hallmark of the hypoxic response. A key regulator of glycolytic flux
      is fructose-2,6-bisphosphate, and its steady state concentration is regulated by
      the action of different isozymes product of four genes (pfkfb1-4). pfkfb3 has
      been found in proliferating cells and tumors, being induced by hypoxia. To
      understand the organization of cis-acting sequences that are responsible for the
      oxygen-regulated pfkfb3 gene, we have studied its 5'-flanking region. Extensive
      analysis of the 5' pfkfb3 promoter sequence revealed the presence of putative
      consensus binding sites for various transcription factors that could play an
      important role in pfkfb3 gene regulation. These DNA consensus sequences included
      estrogen receptor, hypoxia response element (HRE), early growth response, and
      specific protein 1 putative binding sites. Promoter deletion analysis as well as
      putative HREs sequences (wild type and mutated) fused to a c-fos minimal promoter
      unit constructs demonstrate that the sequence located from -1269 to -1297
      relative to the start site is required for hypoxia-inducible factor 1 (HIF-1)
      induction. The effective binding of HIF-1 transcription factor to the HREs at 
      1279 and -1288 was corroborated by electrophoretic mobility shift assay and
      biotinylated oligonucleotide pull-down. In addition, HIF-1alpha null mouse embryo
      fibroblasts transfected with a full-length pfkfb3 promoter-luciferase reporter
      construct further demonstrated that HIF-1 protein was critically involved for
      hypoxia transactivation of this gene. Altogether, these results demonstrate that
      pfkfb3 is a hypoxia-inducible gene that is stimulated through HIF interaction
      with the consensus HRE site in its promoter region.

PMID- 15466860
TI  - Functional regulation of FEZ1 by the U-box-type ubiquitin ligase E4B contributes
      to neuritogenesis.
AB  - E4B (also known as UFD2a) is a mammalian homolog of Saccharomyces cerevisiae
      Ufd2, which was originally described as a ubiquitin chain assembly factor (E4).
      E4B is a U-box-type ubiquitin-protein isopeptide ligase (E3) and likely functions
      as either an E3 or an E4. With a yeast two-hybrid screen, we have now identified
      FEZ1 (fasciculation and elongation protein zeta 1) as a protein that interacts
      with E4B. FEZ1 is implicated in neuritogenesis when phosphorylated by protein
      kinase Czeta (PKCzeta). Interaction between E4B and FEZ1 in mammalian cells was
      enhanced by coexpression of constitutively active PKCzeta. E4B mediated the
      polyubiquitylation of FEZ1 but did not affect its intracellular stability,
      suggesting that such modification of FEZ1 is not a signal for its proteolysis.
      Polyubiquitylation of FEZ1 by E4B required Lys(27) of ubiquitin. Expression of a
      dominant-negative mutant of E4B in rat pheochromocytoma PC12 cells resulted in
      inhibition of neurite extension induced either by nerve growth factor or by
      coexpression of FEZ1 and constitutively active PKCzeta. These findings indicate
      that E4B serves as a ubiquitin ligase for FEZ1 and thereby regulates its function
      but not its degradation.

PMID- 15466861
TI  - Polycystin-1 activates the calcineurin/NFAT (nuclear factor of activated T-cells)
      signaling pathway.
AB  - Regulation of intracellular Ca(2+) mobilization has been associated with the
      functions of polycystin-1 (PC1) and polycystin-2 (PC2), the protein products of
      the PKD1 and PKD2 genes. We have now demonstrated that PC1 can activate the
      calcineurin/NFAT (nuclear factor of activated T-cells) signaling pathway through
      Galpha(q) -mediated activation of phospholipase C (PLC). Transient transfection
      of HEK293T cells with an NFAT promoter-luciferase reporter demonstrated that
      membrane-targeted PC1 constructs containing the membrane proximal region of the C
      terminal tail, which includes the heterotrimeric G protein binding and activation
      domain, can stimulate NFAT luciferase activity. Inhibition of glycogen synthase
      kinase-3beta by LiCl treatment further increased PC1-mediated NFAT activity. PC1
      mediated activation of NFAT was completely inhibited by the calcineurin
      inhibitor, cyclosporin A. Cotransfection of a construct expressing the Galpha(q)
      subunit augmented PC1-mediated NFAT activity, whereas the inhibitors of PLC
      (U73122) and the inositol trisphosphate and ryanodine receptors (xestospongin and
      2-aminophenylborate) and a nonspecific Ca(2+) channel blocker (gadolinium)
      diminished PC1-mediated NFAT activity. PC2 was not able to activate NFAT. An NFAT
      green fluorescent protein nuclear localization assay demonstrated that PC1
      constructs containing the C-tail only or the entire 11-transmembrane spanning
      region plus C-tail induced NFAT-green fluorescent protein nuclear translocation.
      NFAT expression was demonstrated in the M-1 mouse cortical collecting duct cell
      line and in embryonic and adult mouse kidneys by reverse transcriptase-PCR and
      immunolocalization. These data suggest a model in which PC1 signaling leads to a
      sustained elevation of intracellular Ca(2+) mediated by PC1 activation of
      Galpha(q) followed by PLC activation, release of Ca(2+) from intracellular
      stores, and activation of store-operated Ca(2+) entry, thus activating
      calcineurin and NFAT.

PMID- 15466862
TI  - Regioselective nitration of tryptophan by a complex between bacterial nitric
      oxide synthase and tryptophanyl-tRNA synthetase.
AB  - Bacterial nitric-oxide synthase proteins (NOSs) from certain Streptomyces strains
      have been shown to participate in biosynthetic nitration of tryptophanyl moieties
      in vivo (Kers, J. A., Wach, M. J., Krasnoff, S. B., Cameron, K. D., Widom, J.,
      Bukhaid, R. A., Gibson, D. M., and Crane, B. R., and Loria, R. (2004) Nature 429,
      79-82). We report that the complex between Deinococcus radiodurans NOS (deiNOS)
      and an unusual tryptophanyl-tRNA synthetase (TrpRS II) catalyzes the
      regioselective nitration of tryptophan (Trp) at the 4-position. Unlike non
      enzymatic Trp nitration, and similar reactions catalyzed by globins and
      peroxidases, deiNOS only produces the otherwise unfavorable 4-nitro-Trp isomer.
      Although deiNOS alone will catalyze 4-nitro-Trp production, yields are
      significantly enhanced by TrpRS II and ATP. 4-Nitro-Trp formation exhibits
      saturation behavior with Trp (but not tyrosine) and is completely inhibited by
      the addition of the mammalian NOS cofactor (6R)-5,6,7,8-tetrahydro-l-biopterin
      (H(4)B). Trp stimulates deiNOS oxidation of substrate l-arginine (Arg) to the
      same degree as H(4)B. These observations are consistent with a mechanism where
      Trp or a derivative thereof binds in the NOS pterin site, participates in Arg
      oxidation, and becomes nitrated at the 4-position.

PMID- 15466863
TI  - GSK-3 phosphorylation of the Alzheimer epitope within collapsin response mediator
      proteins regulates axon elongation in primary neurons.
AB  - Elevated glycogen synthase kinase-3 (GSK-3) activity is associated with Alzheimer
      disease. We have found that collapsin response mediator proteins (CRMP) 2 and 4
      are physiological substrates of GSK-3. The amino acids targeted by GSK-3 comprise
      a hyperphosphorylated epitope first identified in plaques isolated from Alzheimer
      brain. Expression of wild type CRMP2 in primary hippocampal neurons or SH-SY5Y
      neuroblastoma cells promotes axon elongation. However, a GSK-3-insensitive CRMP2
      mutant has dramatically reduced ability to promote axon elongation, a similar
      effect to pharmacological inhibition of GSK-3. Hence, we propose that
      phosphorylation of CRMP proteins by GSK-3 regulates axon elongation. This work
      provides a direct connection between hyperphosphorylation of these residues and
      elevated GSK-3 activity, both of which are observed in Alzheimer brain.

PMID- 15466864
TI  - A single PXY motif located within the carboxyl terminus of Spt23p and Mga2p
      mediates a physical and functional interaction with ubiquitin ligase Rsp5p.
AB  - Proteasome-dependent processing of the endoplasmic reticulum localized
      transcription factor Spt23p of Saccharomyces cerevisiae generates its
      transcriptionally competent form and requires the WW domain containing Rsp5p
      ubiquitin ligase. Although previous studies documented an Rsp5p-Spt23p
      association in cells, very little is known about the nature of this interaction.
      We report here the identification of an imperfect type I WW domain-binding site
      (LPKY) within the carboxyl-terminal region of Spt23p that is required for Rsp5p
      binding in vitro and in vivo. Deletion of this motif abrogates Rsp5p-induced
      ubiquitination of Spt23p in vitro and reduces ubiquitination of the Spt23p
      precursor in yeast. In addition, the Spt23pDeltaLPKY mutant is inefficiently
      processed and is defective at up-regulating target gene (OLE1) expression in
      cells. Deletion of the corresponding LPKY site within Mga2p, an Spt23p homologue,
      also abrogates Rsp5p binding and Rsp5p-dependent ubiquitination in vitro as well
      as Rsp5p binding and Mga2p polyubiquitination in cells. However, the
      Mga2pDeltaLPKY mutant undergoes efficient proteasome-dependent processing. These
      experiments indicate that the LPKY motif of Spt23p is required for Rsp5p binding,
      Rsp5-induced ubiquitination, proteasome-dependent processing, and its OLE1
      inducing function. They also suggest that the LPKY motif of Mga2p is required for
      Rsp5p binding and ubiquitination, and Rsp5p regulates Mga2p function by a
      mechanism that is independent of providing the partial degradation signal.

PMID- 15466865
TI  - Src-mediated tyrosine phosphorylation of caveolin-1 induces its association with
      membrane type 1 matrix metalloproteinase.
AB  - We have recently shown that stimulation of endothelial cells with vascular
      endothelial growth factor (VEGF) induces dissociation of caveolin-1 from the
      VEGFR-2 receptor, followed by Src family kinase-dependent tyrosine
      phosphorylation of the protein (Labrecque, L., Royal, I., Surprenant, D. S.,
      Patterson, C., Gingras, D., and Beliveau, R. (2003) Mol. Biol. Cell 14, 334-347).
      In this study, we provide evidence that the VEGF-dependent tyrosine
      phosphorylation of caveolin-1 induces interaction of the protein with the
      membrane-type 1 matrix metalloproteinase (MT1-MMP). This interaction requires the
      phosphorylation of caveolin-1 on tyrosine 14 by members of the Src family of
      protein kinases, such as Src and Fyn, because it is completely abolished by
      expression of a catalytically inactive Src mutant or by site-directed mutagenesis
      of tyrosine 14 of caveolin-1. Most interestingly, the association of MT1-MMP with
      phosphorylated caveolin-1 induced the recruitment of Src and a concomitant
      inhibition of the kinase activity of the enzyme, suggesting that this complex may
      be involved in the negative regulation of Src activity. The association of MT1
      MMP with phosphorylated caveolin-1 occurs in caveolae membranes and involves the
      cytoplasmic domain of MT1-MMP because it was markedly reduced by mutation of
      Cys574 and Val582 residues of the cytoplasmic tail of the enzyme. Most
      interestingly, the reduction of the interaction between MT1-MMP and caveolin-1 by
      using these mutants also decreases MT1-MMP-dependent cell locomotion. Overall
      these results indicate that MT1-MMP associates with tyrosine-phosphorylated
      caveolin-1 and that this complex may play an important role in MT1-MMP regulation
      and function.

PMID- 15466866
TI  - The met receptor degradation pathway: requirement for Lys48-linked polyubiquitin
      independent of proteasome activity.
AB  - Acute stimulation of the receptor for the hepatocyte growth factor/scatter factor
      Met leads to receptor monoubiquitination and down-regulation through the
      lysosomal degradation pathway. We have determined that the Met receptor undergoes
      multiple monoubiquitination as opposed to the appendage of polyubiquitin chains.
      Nevertheless, overexpression of ubiquitin in HEK293T cells enhances the rate of
      Met receptor degradation, in contrast to a point mutant of ubiquitin (K48R) that
      cannot form Lys(48)-linked polyubiquitin chains. Furthermore, an enhancement of
      Met degradation is also seen under conditions where the proteasome is inhibited
      by lactacystin. We propose that this reflects polyubiquitin-dependent sorting of
      Met, as the overexpression of ubiquitin but not K48R ubiquitin also restores
      hepatocyte growth factor-dependent phosphorylation of the endosomal coat protein
      Hrs from inhibition by lactacystin. Our data indicate a requirement for K48R
      linked polyubiquitin for Met endosomal trafficking independent of its canonical
      function of targeting for proteasomal degradation.

PMID- 15466868
TI  - Human Rad54 protein stimulates DNA strand exchange activity of hRad51 protein in
      the presence of Ca2+.
AB  - Rad51 and Rad54 proteins play a key role in homologous recombination in
      eukaryotes. Recently, we reported that Ca2+ is required in vitro for human Rad51
      protein to form an active nucleoprotein filament that is important for the search
      of homologous DNA and for DNA strand exchange, two critical steps of homologous
      recombination. Here we find that Ca2+ is also required for hRad54 protein to
      effectively stimulate DNA strand exchange activity of hRad51 protein. This
      finding identifies Ca2+ as a universal cofactor of DNA strand exchange promoted
      by mammalian homologous recombination proteins in vitro. We further investigated
      the hRad54-dependent stimulation of DNA strand exchange. The mechanism of
      stimulation appeared to include specific interaction of hRad54 protein with the
      hRad51 nucleoprotein filament. Our results show that hRad54 protein significantly
      stimulates homology-independent coaggregation of dsDNA with the filament, which
      represents an essential step of the search for homologous DNA. The results
      obtained indicate that hRad54 protein serves as a dsDNA gateway for the hRad51
      ssDNA filament, promoting binding and an ATP hydrolysis-dependent translocation
      of dsDNA during the search for homologous sequences.

PMID- 15466867
TI  - Expression of the vacuolar H+-ATPase 16-kDa subunit results in the Triton X-100
      insoluble aggregation of beta1 integrin and reduction of its cell surface
      expression.
AB  - Vacuolar H(+)-ATPase functions as a vacuolar proton pump and is responsible for
      acidification of intracellular compartments such as the endoplasmic reticulum,
      Golgi, lysosomes, and endosomes. Previous reports have demonstrated that a 16-kDa
      subunit (16K) of vacuolar H(+)-ATPase via one of its transmembrane domains, TMD4,
      strongly associates with beta(1) integrin, affecting beta(1) integrin N-linked
      glycosylation and inhibiting its function as a matrix adhesion receptor. Because
      of this dramatic inhibition of beta(1) integrin-mediated HEK-293 cell motility by
      16K expression, we investigated the mechanism by which 16 kDa was having this
      effect. Using HT1080 cells whose alpha(5)beta(1) integrin-mediated adhesion to
      fibronectin has been extensively studied, the expression of 16 kDa also resulted
      in reduced cell spreading on fibronectin-coated substrates. A pulse-chase study
      of beta(1) integrin biosynthesis indicated that 16K expression down-regulated the
      level of the 110-kDa biosynthetic form of beta(1) integrin (premature form) and,
      consequently, the level of the 130-kDa form of beta(1) integrin (mature form).
      Further experiments showed that the normal levels of association between the
      premature beta(1) integrin form and calnexin were significantly decreased by the
      expression of either 16 kDa or TMD4. Expression of 16 kDa also resulted in a
      Triton X-100-insoluble aggregation of an unusual 87-kDa form of beta(1) integrin.
      Interestingly, both Western blotting and a pulse-chase experiment showed co
      immunoprecipitation of calnexin and 16K. These results indicate that 16K
      expression inhibits beta(1) integrin surface expression and spreading on matrix
      by a novel mechanism that results in reduced levels of functional beta(1)
      integrin.

PMID- 15466869
TI  - Pseudouridylation at position 32 of mitochondrial and cytoplasmic tRNAs requires
      two distinct enzymes in Saccharomyces cerevisiae.
AB  - Cytoplasmic and mitochondrial tRNAs contain several pseudouridylation sites, and
      the tRNA:Psi-synthase acting at position 32 had not been identified in
      Saccharomyces cerevisiae. By combining genetic and biochemical analyses, we
      demonstrate that two enzymes, Rib2/Pus8p and Pus9p, are required for Psi32
      formation in cytoplasmic and mitochondrial tRNAs, respectively. Pus9p acts mostly
      in mitochondria, and Rib2/Pus8p is strictly cytoplasmic. This is the first case
      reported so far of two distinct tRNA modification enzymes acting at the same
      position but present in two different compartments. This peculiarity may be the
      consequence of a gene fusion that occurred during yeast evolution. Indeed,
      Rib2/Pus8p displays two distinct catalytic activities involved in completely
      unrelated metabolism: its C-terminal domain has a DRAP-deaminase activity
      required for riboflavin biogenesis in the cytoplasm, whereas its N-terminal
      domain carries the tRNA:Psi32-synthase activity. Pus9p has only a tRNA:Psi32
      synthase activity and contains a characteristic mitochondrial targeting sequence
      at its N terminus. These results are discussed in terms of RNA:Psi-synthase
      evolution.

PMID- 15466870
TI  - Inhibition of RecA protein by the Escherichia coli RecX protein: modulation by
      the RecA C terminus and filament functional state.
AB  - The RecX protein is a potent inhibitor of RecA activities. We identified several
      factors that affect RecX-RecA interaction. The interaction is enhanced by the
      RecA C terminus and by significant concentrations of free Mg(2+) ion. The
      interaction is also enhanced by an N-terminal His(6) tag on the RecX protein. We
      conclude that RecX protein interacts most effectively with a RecA functional
      state designated A(o) and that the RecA C terminus has a role in modulating the
      interaction. We further identified a C-terminal point mutation in RecA protein
      (E343K) that significantly alters the interaction between RecA and RecX proteins.

PMID- 15466871
TI  - Structure of the topoisomerase IV C-terminal domain: a broken beta-propeller
      implies a role as geometry facilitator in catalysis.
AB  - Bacteria possess two closely related yet functionally distinct essential type IIA
      topoisomerases (Topos). DNA gyrase supports replication and transcription with
      its unique supercoiling activity, whereas Topo IV preferentially relaxes (+)
      supercoils and is a decatenating enzyme required for chromosome segregation. Here
      we report the crystal structure of the C-terminal domain of Topo IV ParC subunit
      (ParC-CTD) from Bacillus stearothermophilus and provide a structure-based
      explanation for how Topo IV and DNA gyrase execute distinct activities. Although
      the topological connectivity of ParC-CTD is similar to the recently determined
      CTD structure of DNA gyrase GyrA subunit (GyrA-CTD), ParC-CTD surprisingly folds
      as a previously unseen broken form of a six-bladed beta-propeller. Propeller
      breakage is due to the absence of a DNA gyrase-specific GyrA box motif, resulting
      in the reduction of curvature of the proposed DNA binding region, which explains
      why ParC-CTD is less efficient than GyrA-CTD in mediating DNA bending, a
      difference that leads to divergent activities of the two homologous enzymes.
      Moreover, we found that the topology of the propeller blades observed in ParC-CTD
      and GyrA-CTD can be achieved from a concerted beta-hairpin invasion-induced fold
      change event of a canonical six-bladed beta-propeller; hence, we proposed to name
      this new fold as "hairpin-invaded beta-propeller" to highlight the high degree of
      similarity and a potential evolutionary linkage between them. The possible role
      of ParC-CTD as a geometry facilitator during various catalytic events and the
      evolutionary relationships between prokaryotic type IIA Topos have also been
      discussed according to these new structural insights.

PMID- 15466873
TI  - DNA helicase activity of the RecD protein from Deinococcus radiodurans.
AB  - The bacterium Deinococcus radiodurans is extremely resistant to high levels of
      DNA-damaging agents, including gamma rays and ultraviolet light that can lead to
      double-stranded DNA breaks. Surprisingly, the organism does not appear to have a
      RecBCD enzyme, an enzyme that is critical for double-strand break repair in many
      other bacteria. The D. radiodurans genome does encode a protein whose closest
      characterized homologues are RecD subunits of RecBCD enzymes in other bacteria.
      We have purified this novel D. radiodurans RecD protein and characterized its
      biochemical activities. The D. radiodurans RecD protein is a DNA helicase that
      unwinds short (20 base pairs) DNA duplexes with either a 5'-single-stranded tail
      or a forked end, but not blunt-ended or 3'-tailed duplexes. Duplexes with 10-12
      nucleotide (nt) 5'-tails are good unwinding substrates and are bound tightly,
      while DNA with shorter tails (4-8 nt) are poor unwinding substrates and are bound
      much less tightly. The RecD protein is much less efficient at unwinding slightly
      longer substrates (52 or 76 base pairs, with 12 nt 5'-tails). Unwinding of the
      longer substrates is stimulated somewhat (4-5-fold) by the single-stranded DNA
      binding protein from D. radiodurans. These results show that the D. radiodurans
      RecD protein is a DNA helicase with 5'-3' polarity and low processivity.

PMID- 15466872
TI  - APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus
      replication.
AB  - In the human genome the apolipoprotein B mRNA-editing enzyme catalytic
      polypeptide (APOBEC)3 gene has expanded into a tandem array of genes termed
      APOBEC3A-G. Two members of this family, APOBEC3G and APOBEC3F, have been found to
      have potent activity against virion infectivity factor deficient (Deltavif) human
      immunodeficiency virus 1 (HIV-1). These enzymes become encapsidated in Deltavif
      HIV-1 virions and in the next round of infection deaminate the newly synthesized
      reverse transcripts. The lentiviral Vif protein prevents the deamination by
      inducing the degradation of APOBEC3G and APOBEC3F. We report here that two
      additional APOBEC3 family members, APOBEC3B and APOBEC3C, have potent antiviral
      activity against simian immuno-deficiency virus (SIV), but not HIV-1. Both
      enzymes were encapsidated in HIV-1 and SIV virions and were active against
      Deltavif SIV(mac) and SIV(agm). SIV Vif neutralized the antiviral activity of
      APOBEC3C, but not that of APOBEC3B. APOBEC3B induced abundant G --> A mutations
      in both wild-type and Deltavif SIV reverse transcripts. APOBEC3C induced
      substantially fewer mutations. APOBEC3F was found to be active against SIV and
      sensitive to SIV(mac) Vif. These findings raise the possibility that the
      different APOBEC3 family members function to neutralize specific lentiviruses.

PMID- 15466874
TI  - Regulatory role of glycogen synthase kinase 3 for transcriptional activity of
      ADD1/SREBP1c.
AB  - Adipocyte determination- and differentiation-dependent factor 1 (ADD1) plays
      important roles in lipid metabolism and insulin-dependent gene expression.
      Because insulin stimulates carbohydrate and lipid synthesis, it would be
      important to decipher how the transcriptional activity of ADD1/SREBP1c is
      regulated in the insulin signaling pathway. In this study, we demonstrated that
      glycogen synthase kinase (GSK)-3 negatively regulates the transcriptional
      activity of ADD1/SREBP1c. GSK3 inhibitors enhanced a transcriptional activity of
      ADD1/SREBP1c and expression of ADD1/SREBP1c target genes including fatty acid
      synthase (FAS), acetyl-CoA carboxylase 1 (ACC1), and steroyl-CoA desaturase 1
      (SCD1) in adipocytes and hepatocytes. In contrast, overexpression of GSK3beta
      down-regulated the transcriptional activity of ADD1/SREBP1c. GSK3 inhibitor
      mediated ADD1/SREBP1c target gene activation did not require de novo protein
      synthesis, implying that GSK3 might affect transcriptional activity of
      ADD1/SREBP1c at the level of post-translational modification. Additionally, we
      demonstrated that GSK3 efficiently phosphorylated ADD1/SREBP1c in vitro and in
      vivo. Therefore, these data suggest that GSK3 inactivation is crucial to confer
      stimulated transcriptional activity of ADD1/SREBP1c for insulin-dependent gene
      expression, which would coordinate lipid and glucose metabolism.

PMID- 15466875
TI  - Bi-phasic growth patterns in rice.
AB  - BACKGROUND AND AIMS: When examining the growth patterns of rice crops for a 5
      year period, it was found that the time course of accumulation of above-ground
      dry matter did not follow a simple sigmoid curve as expected for a monocarpic
      plant. Instead, there was a decrease in growth around flowering, followed by an
      increase and then a final decrease of growth at crop maturity. There are two
      nearly equal phases of growth in rice, with about half of the first phase of
      vegetative growth preceding reproductive growth. METHODS: Logistic curves were
      fitted separately to the vegetative parts of the crop and to the reproductive
      parts (the panicle). When the curves were summed, the combined curve gave a good
      description of the time course of above-ground dry matter, capturing the pause in
      growth and its resumption. The overall pattern of growth can be seen to be the
      result of this bi-phasic nature of the crop. KEY RESULTS: Variations in the
      panicle phase of growth were shown to be largely a consequence of year-to-year
      variations in the weather, whereas the vegetative phase seemed largely
      independent of those variations. CONCLUSIONS: Analysing rice growth as two
      components, each with a logistic curve, provides insight into the growth
      processes of the plant and the pattern of yield formation.

PMID- 15466876
TI  - Soybean (Glycine max) pollen germination characteristics, flower and pollen
      morphology in response to enhanced ultraviolet-B radiation.
AB  - BACKGROUND AND AIMS: Ultraviolet-B (UV-B) radiation effect on reproductive parts
      of the plants has received little attention. We studied the influence of UV-B
      radiation on flower and pollen morphology, pollen production and in vitro pollen
      germination and tube growth of six genotypes of soybean (Glycine max). METHODS:
      Soybean genotypes were investigated by growing them under four levels of
      biologically effective UV-B radiation of 0 (control), 5, 10 and 15 kJ m(-2) d(-1)
      in sunlit controlled-environment chambers. KEY RESULTS: Reductions in lengths of
      flower, standard petal, and staminal column along with reduced pollen production,
      germination and tube growth were observed in all genotypes with increasing UV-B
      radiation. Combined response index (CRI), the sum of percentage relative
      responses in flower size, pollen production, pollen germination and tube growth
      due to UV-B radiation varied with UV-B dosage: -67 to -152 with 5 kJ m(-2) d(-1),
      -90 to -212 with 10 kJ m(-2) d(-1), and -118 to -248 with 15 kJ m(-2) d(-1) of UV
      B compared to controls. Genotypes were classified based on the UV-B sensitivity
      index (USI) calculated as CRI per unit UV-B, where D 90-9216, DG 5630RR and D 88
      5320 were classified as tolerant (USI > -7.43), and DP 4933RR, Stalwart III and
      PI 471938 were sensitive (USI < -7.43) in their response to UV-B radiation.
      Pollen grains produced in plants grown at 15 kJ m(-2) d(-1) UV-B radiation were
      shrivelled and lacked apertures compared to control and other UV-B treatments in
      both sensitive and tolerant genotypes, and the differences were more conspicuous
      in the sensitive genotype (PI 471938) than in the tolerant genotype (D 90-9216).
      The number of columellae heads of the exine was reduced with increasing UV-B
      radiation. CONCLUSIONS: Soybean genotypes varied in their reproductive response
      to UV-B radiation. The identified UV-B tolerant genotypes could be used in future
      breeding programmes.

PMID- 15466877
TI  - Contrasting growth changes in two dominant species of a Mediterranean shrubland
      submitted to experimental drought and warming.
AB  - BACKGROUND AND AIMS: Climate projections predict drier and warmer conditions in
      the Mediterranean basin in the next decades. The possibility of such climatic
      changes modifying the growth of two Mediterranean species, Erica multiflora and
      Globularia alypum, which are common components of Mediterranean shrublands, was
      assessed. METHODS: A field experiment was performed from March 1999 to March 2002
      to prolong the drought period and to increase the night-time temperature in a
      Mediterranean shrubland, where E. multiflora and G. alypum are the dominant
      species. Annual growth in stem diameter and length of both species was measured
      and annual stem biomass production was estimated for 1999, 2000 and 2001. Plant
      seasonal growth was also assessed. KEY RESULTS: On average, drought treatment
      reduced soil moisture 22 %, and warming increased temperature by 0.7-1.6 degrees
      C. Erica multiflora plants in the drought treatment showed a 46 % lower annual
      stem elongation than controls. The decrease in water availability also reduced by
      31 % the annual stem diameter increment and by 43 % the annual stem elongation of
      G. alypum plants. New shoot growth of G. alypum was also strongly reduced.
      Allometrically estimated biomass production was decreased by drought in both
      species. Warming treatment produced contrasting effects on the growth patterns of
      these species. Warmer conditions increased, on average, the stem basal diameter
      growth of E. multiflora plants by 35 %, raising also their estimated stem biomass
      production. On the contrary, plants of G. alypum in the warming treatment showed
      a 14 % lower annual stem growth in basal diameter and shorter new shoots in
      spring compared with controls. CONCLUSIONS: The results indicate changes in the
      annual productivity of these Mediterranean shrubs under near future drier and
      warmer conditions. They also point to alterations in their competitive abilities,
      which could lead to changes in the species composition of these ecosystems in the
      long term.

PMID- 15466879
TI  - The influence of hepatitis C and iron replacement therapy on plasma pentosidine
      levels in haemodialysis patients.
AB  - BACKGROUND: Chronic liver disease and intravenous (i.v.) iron therapy can enhance
      oxidative stress. The aim of this study was to assess the influence of hepatitis
      C virus (HCV) and i.v. iron administration on oxidative stress in chronic
      haemodialysis (HD) patients. METHODS: A total of 115 HD patients (47% males, age
      47 +/- 13 years) were placed in two groups according to the presence (HCV(+)) or
      absence (HCV(-)) of serum antibodies against HCV. Plasma pentosidine, high
      sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and alanine
      aminotransferase (ALT) levels were measured. The patients were also analysed
      according to the tertiles of serum levels of ferritin: group 1 (ferritin <380
      ng/ml), group 2 (ferritin 380-750 ng/ml) and group 3 (ferritin >750 ng/ml). The
      cumulative iron dose was recorded during 6 months prior to the study. RESULTS:
      HCV(+) patients had significantly higher levels of plasma pentosidine and ALT
      than HCV(-) patients. Age, gender, serum albumin, IL-6 and hsCRP did not differ
      according to HCV serology. The levels of pentosidine were related to the ferritin
      levels and were significantly higher in group 3 compared with group 1. Moreover,
      the cumulative dose of iron was significantly higher in group 3 than in group 1.
      Plasma pentosidine showed a positive correlation with age, HCV and ferritin. In a
      stepwise backward multiple regression model, age and HCV were independent
      predictors of pentosidine levels. CONCLUSION: HCV in HD patients is associated
      with increased pentosidine levels, possibly reflecting increased oxidative
      stress. The association between pentosidine and ferritin levels may suggest an
      impact of i.v. iron therapy.

PMID- 15466878
TI  - Molecular genetics of disease resistance in cereals.
AB  - AIMS: This Botanical Briefing attempts to summarize what is currently known about
      the molecular bases of disease resistance in cereal species and suggests future
      research directions. SCOPE: An increasing number of resistance (R) genes have
      been isolated from rice, maize, wheat and barley that encode both structurally
      related and unique proteins. This R protein diversity may be attributable to the
      different modus operandi employed by pathogen species in some cases, but it is
      also a consequence of multiple defence strategies being employed against
      phytopathogens. Mutational analysis of barley has identified additional genes
      required for activation of an R gene-mediated defence response upon pathogen
      infection. In some instances very closely related barley R proteins require
      different proteins for defence activation, demonstrating that, within a single
      plant species, multiple resistance signalling pathways and different resistance
      strategies have evolved to confer protection against a single pathogen species.
      Despite the apparent diversity of cereal resistance mechanisms, some of the
      additional molecules required for R protein function are conserved amongst cereal
      and dicotyledonous species and even other eukaryotic species. Thus the derivation
      of functional homologues and interacting partner proteins from other species is
      contributing to the understanding of resistance signalling in cereals. The
      potential and limit of utilizing the rice genome sequence for further R gene
      isolation from cereal species is also considered, as are the new biotechnological
      possibilities for disease control arising from R gene isolation. CONCLUSIONS:
      Molecular analyses in cereals have further highlighted the complexity of plant
      pathogen co-evolution and have shown that numerous active and passive defence
      strategies are employed by plants against phytopathogens. Many advances in
      understanding the molecular basis of disease resistance in cereals have focused
      on monogenic resistance traits. Future research targets are likely to include
      less experimentally tractable, durable polygenic resistances and nonhost
      resistance mechanisms.

PMID- 15466880
TI  - Pamidronate used to attenuate post-renal transplant bone loss is not associated
      with renal dysfunction.
AB  - BACKGROUND: Pamidronate is a second-generation bisphosphonate that has been used
      to attenuate post-renal transplant bone loss, but its effect on the function of
      the renal allograft is unclear. Therefore, we evaluated the long-term renal
      function in 57 subjects who had participated in a prospective, randomized
      clinical trial using pamidronate to attenuate bone loss in the renal transplant
      recipient. METHODS: Thirty subjects (PAM) received intravenous pamidronate, 60 mg
      at baseline post-transplant and 30 mg in months 1, 2, 3 and 6 post-transplant,
      while 27 subjects (CON) did not receive pamidronate. We followed renal function,
      need for renal replacement therapy following transplant rejection, and mortality
      for 3 years following the start of the original study. RESULTS: PAM did not have
      increased incidence of renal dysfunction or mortality compared with CON at any
      time point during the 3 years of follow-up. The incidence of proteinuria was also
      not different between the two groups. CONCLUSIONS: The prophylactic use of
      pamidronate in the above doses to attenuate bone loss in renal transplant
      recipients is not associated with higher incidence of renal dysfunction or
      mortality in a 3 year follow-up study. These findings may support the use of
      bisphosphonates in the treatment of early renal transplant-related bone loss.

PMID- 15466881
TI  - Routine use of mupirocin at the peritoneal catheter exit site and mupirocin
      resistance: still low after 7 years.
AB  - OBJECTIVE: The purpose of this study (the third in a series of similar studies)
      is to evaluate the prevalence of Staphylococcus aureus (SA), methicillin
      resistant SA (MRSA) and mupirocin-resistant SA (MuRSA) carriers in a peritoneal
      dialysis centre where patients have been instructed to use prophylactic mupirocin
      ointment at the catheter exit site over the last 7 years. METHODS: Swabs were
      taken from catheter exit site, nares, axillae and groin in 147 chronic peritoneal
      dialysis out-patients between November 2003 and January 2004. Axillae/groin and
      nasal samples were pooled and cultured in the same medium, whereas exit site
      swabs were cultured separately. All SA isolated were tested for methicillin and
      mupirocin resistance using oxacillin screening plates and E-test strips. RESULTS:
      Sixteen of 147 patients (10.9%) were found to be SA carriers: of these 13 (8.8%)
      had a positive nasal/axillae/groin culture; two (1.4%) had both
      nasal/axillae/groin- and exit site-positive culture; and one (0.7%) had only exit
      site-positive culture. In these 16 SA carriers, we found mupirocin-resistant
      strains (MuRSA) in four patients (25%) and MRSA in two patients (12.5%). Among
      the four MuRSA carriers, one had both nasal/axillae/groin- and exit site-positive
      culture and three had only nasal/axillae/groin-positive culture. Three high-level
      resistance and one low-level resistance MuRSA carriers were isolated. One MuRSA
      strain was also methicillin resistant. All MRSA strains were sensitive to
      vancomycin and rifampicin. CONCLUSION: After 7 years' routine use of prophylactic
      mupirocin ointment at the catheter exit site in non-selected chronic peritoneal
      dialysis patients, MuRSA was found in 25% of SA strains isolated or in 2.7% of
      the patients. Compared with our previous study, 3 years earlier, there is no
      significant increase in the MuRSA prevalence in peritoneal dialysis patients who
      routinely apply mupirocin ointment at the catheter exit site.

PMID- 15466882
TI  - Blockade of the renin-angiotensin system increases graft survival in patients
      with chronic allograft nephropathy.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN) is the leading cause of late
      allograft failure, with only limited treatment options. Blockade of the renin
      angiotensin system (RAS) decreases progression in diabetic and non-diabetic renal
      disease, but the effect on CAN is as yet unclear. Therefore, we have studied
      retrospectively the effect of RAS blockade on renal survival in patients with
      biopsy-proven CAN. METHODS: The medical records of 72 patients with biopsy-proven
      CAN were evaluated with regard to time course of graft function, proteinuria,
      blood pressure, and antihypertensive and immunosuppressive treatment. Cox's
      proportional hazards model was used for analysing renal graft survival after the
      index biopsy. RESULTS: On univariate analysis, histological determinants
      influencing renal survival were the chronic interstitial and chronic tubular
      score, and clinical parameters were the serum creatinine level at the time of the
      biopsy, the relative change in serum creatinine level between 12 months post
      transplantation and at the time of the biopsy, mean systolic and diastolic blood
      pressure after the biopsy, and RAS blockade by angiotensin-converting enzyme
      inhibitor or angiotensin receptor blocker. On multivariate analysis, graft
      outcome was influenced by the relative change in serum creatinine level between
      12 months post-transplantation and the time of the index biopsy, the urinary
      protein excretion, the mean diastolic blood pressure after the index biopsy, and
      RAS blockade. Renal graft survival after treatment with RAS blockade was 6.3 (0.9
      10.9) years as opposed to 1.8 (0.1-6.7) years in untreated patients (P = 0.003).
      CONCLUSION: RAS blockade increases graft survival in CAN. In view of the limited
      treatment options for CAN, this finding is of importance and needs confirmation
      by a prospective randomized trial.

PMID- 15466883
TI  - Increased internalisation and degradation of GLT-1 glial glutamate transporter in
      a cell model for familial amyotrophic lateral sclerosis (ALS).
AB  - It has been suggested that glutamate-induced excitotoxicity plays a central role
      in the development of motor neuron diseases such as amyotrophic lateral sclerosis
      (ALS). The GLT-1 isoform of the glutamate transporter gene family is the most
      important transporter involved in keeping extracellular glutamate concentration
      below neurotoxic levels. Its loss and an increase in extracellular glutamate has
      been documented in cases of sporadic and familial ALS, as well as in animal
      models expressing ALS-linked Cu2+-Zn2+ superoxide dismutase (SOD1) mutations, but
      the underlying molecular mechanisms are still unclear. We developed and
      characterised a cell model consisting of polarised epithelial Madin-Darby Canine
      Kidney (MDCK) cell lines stably expressing wild-type SOD1 or the ALS-linked SOD1
      G93A mutant, and analysed the expression of glutamate transporters after
      transient transfection of the corresponding cDNAs. Like ALS patients and animal
      models of ALS, the G93A-expressing MDCK cell system showed reduced total glial
      GLT-1 expression, with no change in the expression of the neuronal EAAC1
      glutamate transporter isoform. Morphological analysis revealed the intracellular
      redistribution of GLT-1 to acidic compartments, whereas the surface distribution
      of other glutamate transporters (neuronal EAAC1 and glial GLAST) was not
      affected. Moreover, mutant SOD1 affected the cytosolic tail of GLT-1 because
      reduced protein expression of EAAC-GLT but not GLT-EAAC chimeras was found in
      G93A-expressing cell lines. GLT-1 downregulation was greatly induced by
      inhibition of protein synthesis, and prevented by treatment with chloroquine
      aimed at inhibiting the activity of acidic degradative compartments. Negligible
      effect on the protein level or distribution of GLT-1 was observed in cells
      overexpressing wild-type SOD1. The specific decrease in the GLT-1 isoform of
      glutamate transporters is therefore recapitulated in G93A-expressing MDCK cell
      lines, thus suggesting an autonomous cell mechanism underlying the loss of GLT-1
      in ALS. Our data indicate that the continuous expression of mutant SOD1 causes
      the downregulation of GLT-1 by increasing the internalisation and degradation of
      the surface transporter, and suggest that the cytosolic tail of GLT-1 is required
      to target the transporter to degradation.

PMID- 15466884
TI  - Nuclear localisation of the G-actin sequestering peptide thymosin beta4.
AB  - Thymosin beta4 is regarded as the main G-actin sequestering peptide in the
      cytoplasm of mammalian cells. It is also thought to be involved in cellular
      events like cancerogenesis, apoptosis, angiogenesis, blood coagulation and wound
      healing. Thymosin beta4 has been previously reported to localise intracellularly
      to the cytoplasm as detected by immunofluorescence. It can be selectively
      labelled at two of its glutamine-residues with fluorescent Oregon Green
      cadaverine using transglutaminase; however, this labelling does not interfere
      with its interaction with G-actin. Here we show that after microinjection into
      intact cells, fluorescently labelled thymosin beta4 has a diffuse cytoplasmic and
      a pronounced nuclear staining. Enzymatic cleavage of fluorescently labelled
      thymosin beta4 with AsnC-endoproteinase yielded two mono-labelled fragments of
      the peptide. After microinjection of these fragments, only the larger N-terminal
      fragment, containing the proposed actin-binding sequence exhibited nuclear
      localisation, whereas the smaller C-terminal fragment remained confined to the
      cytoplasm. We further showed that in digitonin permeabilised and extracted cells,
      fluorescent thymosin beta4 was solely localised within the cytoplasm, whereas it
      was found concentrated within the cell nuclei after an additional Triton X100
      extraction. Therefore, we conclude that thymosin beta4 is specifically
      translocated into the cell nucleus by an active transport mechanism, requiring an
      unidentified soluble cytoplasmic factor. Our data furthermore suggest that this
      peptide may also serve as a G-actin sequestering peptide in the nucleus, although
      additional nuclear functions cannot be excluded.

PMID- 15466885
TI  - New sorting nexin (SNX27) and NHERF specifically interact with the 5-HT4a
      receptor splice variant: roles in receptor targeting.
AB  - The 5-hydroxytryptamine type 4 receptor (5-HT4R) is involved in learning,
      feeding, respiratory control and gastrointestinal transit. This receptor is one
      of the G-protein-coupled receptors for which alternative mRNA splicing generates
      the most variants that differ in their C-terminal extremities. Some 5-HT4R
      variants (a, e and f) express canonical PDZ ligands at their C-termini. Here, we
      have examined whether some mouse 5-HT4R variants associate with specific sets of
      proteins, using a proteomic approach based on peptide-affinity chromatography,
      two-dimensional electrophoresis and mass spectrometry. We have identified ten
      proteins that interact specifically with the 5-HT4(a)R and three that only
      associate with the 5-HT4(e)R. Most of them are PDZ proteins. Among the proteins
      that associated specifically with the 5-HT4(a)R variant, NHERF greatly modified
      its subcellular localization. Moreover, NHERF recruited the 5-HT4(a)R to
      microvilli, where it localized with activated ezrin, consistent with the role of
      5-HT4(a)R in cytoskeleton remodelling. The 5-HT4(a)R also interacted with both
      the constitutive and inducible (upon methamphetamine treatment) forms of the
      recently cloned sorting nexin 27 (SNX27a and b, respectively). We found that
      SNX27a redirected part of 5-HT4(a)R to early endosomes. The interaction of the 5
      HT4R splice variants with distinct sets of PDZ proteins might specify their
      cellular localization as well as their signal transduction properties.

PMID- 15466886
TI  - alpha4beta1- and alpha6beta1-integrins are functional receptors for midkine, a
      heparin-binding growth factor.
AB  - Midkine is a heparin-binding growth factor that promotes the growth, survival,
      migration and differentiation of various target cells. So far, receptor-type
      protein tyrosine phosphatase zeta, low-density-lipoprotein-receptor-related
      protein and anaplastic lymphoma kinase have been identified as receptors for
      midkine. We found beta1 integrin in midkine-binding proteins from 13-day-old
      mouse embryos. beta1-Integrin bound to a midkine-agarose column and was eluted
      mostly with EDTA. Further study revealed that the alpha-subunits capable of
      binding to midkine were alpha4 and alpha6. Purified alpha4beta1- and alpha6beta1
      integrins bound midkine. Anti-alpha4 antibody inhibited the midkine-dependent
      migration of osteoblastic cells, and anti-alpha6 antibody inhibited the midkine
      dependent neurite outgrowth of embryonic neurons. After midkine treatment,
      tyrosine phosphorylation of paxillin, an integrin-associated molecule, was
      transiently increased in osteoblastic cells. Therefore, we concluded that
      alpha4beta1- and alpha6beta1-integrins are functional receptors for midkine. We
      observed that the low-density-lipoprotein-receptor-related-protein-6 ectodomain
      was immunoprecipitated with alpha6beta1-integrin and alpha4beta1-integrin. The
      low-density-lipoprotein-receptor-related-protein-6 ectodomain was also
      immunoprecipitated with receptor-type protein tyrosine phosphatase zeta.
      alpha4beta1- and alpha6beta1-Integrins are expected to co-operate with other
      midkine receptors, possibly in a multimolecular complex that contains other
      midkine receptors.

PMID- 15466887
TI  - Demonstration of BACE (beta-secretase) phosphorylation and its interaction with
      GGA1 in cells by fluorescence-lifetime imaging microscopy.
AB  - beta-Secretase (BACE) carries out the first of two proteolysis steps to generate
      the amyloid-beta peptides that accumulate in the senile plaques in Alzheimer's
      disease (AD). Because most BACE activity occurs in endosomes, signals regulating
      its trafficking to these compartments are important to an understanding of AD
      pathogenesis. A DISLL sequence near the BACE C-terminus mediates binding of BACE
      to the VHS domains of Golgi-localized gamma-ear-containing ARF-binding (GGA)
      proteins, which are involved in the sorting of proteins to endosomes.
      Phosphorylation of the motif's serine residue regulates BACE recycling back to
      the cell surface from early endosomes and enhances the interaction of BACE with
      GGA proteins in isolated protein assays. We found that BACE phosphorylation
      influences BACE-GGA interactions in cells using a new fluorescence-resonance
      energy-transfer-based assay of protein proximity, fluorescence lifetime imaging.
      Although serine-phosphorylated BACE was distributed throughout the cell,
      interaction of GGA1 with the wild-type protein occurred in juxtanuclear
      compartments. Pseudo-phosphorylated and non-phosphorylated BACE mutants remained
      localized with GGA1 in the Golgi body, but the latter mutation diminished the two
      proteins' FRET signal. Because BACE phosphorylated at serine residues can be
      identified in human brain, these data suggest that serine phosphorylation of BACE
      is a physiologically relevant post-translational modification that regulates
      trafficking in the juxtanuclear compartment by interaction with GGA1.

PMID- 15466888
TI  - Insulin but not PDGF relies on actin remodeling and on VAMP2 for GLUT4
      translocation in myoblasts.
AB  - Insulin promotes the translocation of glucose transporter 4 (GLUT4) from
      intracellular pools to the surface of muscle and fat cells via a mechanism
      dependent on phosphatidylinositol (PtdIns) 3-kinase, actin cytoskeletal
      remodeling and the v-SNARE VAMP2. The growth factor PDGF-BB also robustly
      activates PtdIns 3-kinase and induces actin remodeling, raising the question of
      whether it uses similar mechanisms to insulin in mobilizing GLUT4. In L6
      myoblasts stably expressing Myc-tagged GLUT4, neither stimulus affected the rate
      of GLUT4 endocytosis, confirming that they act primarily by enhancing exocytosis
      to increase GLUT4 at the cell surface. Although surface GLUT4myc in response to
      insulin peaked at 10 minutes and remained steady for 30 minutes, PDGF action was
      transient, peaking at 5 minutes and disappearing by 20 minutes. These GLUT4myc
      translocation time courses mirrored that of phosphorylation of Akt by the two
      stimuli. Interestingly, insulin and PDGF caused distinct manifestations of actin
      remodeling. Insulin induced discrete, long (>5 microm) dorsal actin structures at
      the cell periphery, whereas PDGF induced multiple short (<5 microm) dorsal
      structures throughout the cell, including above the nucleus. Latrunculin B,
      cytochalasin D and jasplakinolide, which disrupt actin dynamics, prevented
      insulin- and PDGF-induced actin remodeling but significantly inhibited GLUT4myc
      translocation only in response to insulin (75-85%, P<0.05), not to PDGF (20-30%
      inhibition). Moreover, transfection of tetanus toxin light chain, which cleaves
      the v-SNAREs VAMP2 and VAMP3, reduced insulin-induced GLUT4myc translocation by
      >70% but did not affect the PDGF response. These results suggest that insulin and
      PDGF rely differently on the actin cytoskeleton and on tetanus-toxin-sensitive
      VAMPs for mobilizing GLUT4.

PMID- 15466889
TI  - Caveolin-1 and MAL are located on prostasomes secreted by the prostate cancer PC
      3 cell line.
AB  - MAL, BENE and MAL2 are raft-associated integral membrane proteins of the MAL
      family of proteins involved in membrane trafficking processes. We show here that
      the human prostate carcinoma PC-3 cell line expresses the transcripts for the
      three proteins simultaneously. MAL, BENE and MAL2 co-fractionated with caveolin-1
      in the raft fraction of PC-3 cells, and immunofluorescence analysis showed
      colocalization of these proteins with caveolin-1 in a multivesicular
      intracellular compartment. Markers of the Golgi apparatus, early and recycling
      endosomes and lipid droplets were excluded from this compartment. Prostate
      epithelial cells contain vesicular organelles enriched in raft components named
      prostasomes that are secreted in the prostate fluid. Interestingly, the
      prostasome fraction isolated from the culture supernatant of PC-3 cells consisted
      mainly of 30-130 nm cup-shaped vesicles that were positive for MAL, caveolin-1
      and CD59, a glycosylphosphatidylinositol-anchored protein previously found in
      prostasomes. CD63, an integral membrane protein found in multivesicular
      bodies/lysosomes and secretory granules was also found in PC-3 cell-derived
      prostasomes. Prostasome secretion was not inhibited by brefeldin A, a compound
      that blocks the conventional secretory pathway. However, wortmannin, an inhibitor
      of phosphatidylinositol-3 kinase, reduced the secretion of prostasomes in PC-3
      cells. Our results suggest that MAL family proteins are associated with caveolin
      1 in a multivesicular compartment that may be involved in prostasomal secretion
      in PC-3 cells.

PMID- 15466890
TI  - Skeletal muscle satellite cells can spontaneously enter an alternative
      mesenchymal pathway.
AB  - We show that muscle satellite cells, traditionally considered as committed
      myogenic precursors, are comprised of Pax7-expressing progenitors that preserve a
      mesenchymal repertoire extending beyond a mere myogenic potential. Mouse
      satellite cells from freshly isolated single myofibers, cultured individually in
      serum-rich growth medium, produced myogenic and non-myogenic clones. Only the
      myogenic clones expressed muscle-specific transcription factors and formed
      myotubes. Pax7 was initially expressed in all clones, but subsequently was
      associated only with the myogenic clones. Some cells in the non-myogenic clones
      expressed alpha-smooth muscle actin and nestin whereas others differentiated into
      mature adipocytes. This type of cell composition mirrors characteristics of
      mesenchymal stem cell progeny. Overall, individual myofibers persistently gave
      rise to both clonal phenotypes, but the ratio of myogenic to non-myogenic clones
      randomly varied among fibers. This randomness indicates that clonal dichotomy
      reflects satellite cell suppleness rather than pre-fated cell heterogeneity. We
      conclude that satellite cells possess mesenchymal plasticity, being able to
      commit either to myogenesis or to a mesenchymal alternative differentiation (MAD)
      program.

PMID- 15466891
TI  - Caenorhabditis elegans UBC-2 functions with the anaphase-promoting complex but
      also has other activities.
AB  - The anaphase-promoting complex or cyclosome (APC/C) is a multi-subunit ubiquitin
      ligase that regulates the eukaryotic cell cycle. APC/C belongs to the RING finger
      class of ubiquitin ligases that function by interacting with a ubiquitin
      conjugating enzyme (Ubc), thus inciting the Ubc to transfer ubiquitin onto a
      target protein. Extensive studies with APC/C in other organisms have identified
      several possible Ubcs that might function as partners for APC/C. This report
      presents phenotypic and biochemical evidence showing that, in Caenorhabditis
      elegans, UBC-2 interacts specifically with the APC/C. This conclusion is based on
      three lines of evidence: first, the RNAi phenotype of ubc-2 is indistinguishable
      from RNAi phenotypes of APC/C subunits; second, RNAi of ubc-2 but not other Ubcs
      enhances the phenotype of hypomorphic APC/C mutants; third, purified UBC-2 and
      APC-11, the RING finger subunit of the APC/C, show robust ubiquitination activity
      in in vitro assays. APC-11 interaction is specific for UBC-2 as ubiquitination is
      not seen when APC-11 is combined other C. elegans Ubcs. As expected from the Ubc
      that functions with the APC/C, ubc-2(RNAi) produces metaphase blocks in both
      mitotic germ cells and in meiotic divisions of post-fertilization oocytes. In
      addition, ubc-2(RNAi) results in two germline phenotypes that appear to be
      unrelated to the APC/C: an expanded transition zone indicative of a pre-pachytene
      meiotic arrest and endo-reduplicated oocytes indicative of a problem in ovulation
      or oocyte-soma interactions.

PMID- 15466892
TI  - The novel mouse connexin39 gene is expressed in developing striated muscle
      fibers.
AB  - The recently identified mouse connexin39 (mCx39) gene encodes a peptide of 364
      amino acids that shows only 61% sequence similarity to its putative human
      orthologue connexin40.1 (hCx40.1). The coding regions of mCx39 and hCx40.1 are
      located on two different exons as described for murine and human connexin36.
      Northern blot and RT-PCR analyses revealed that mCx39 is expressed after
      embryonic day (ED) 13.5 up to birth and is absent from the adult stage.
      Polyclonal antibodies raised to a peptide corresponding to the 16 C-terminal
      amino acid residues detected a protein band of about 40 kDa apparent molecular
      mass in lysates of several embryonic tissues. In sections of ED14.5, ED16.5 and
      neonatal (P0) tissues, immunofluorescent signals were prominent between myotubes
      in the developing diaphragm, within the intercostal muscle, in the region around
      the occipital bone, as well as in muscles of the limb, tongue and connective
      tissue around the eye. These antibodies yielded punctate signals on apposed
      plasma membranes of HeLa cells transfected with Cx39 cDNA but did not react with
      wild-type cells. Furthermore, no intercellular permeation of microinjected
      neurobiotin and other tracers could be detected in Cx39 transfected HeLa cells.
      However, after microinjection of Alexa488 into myotubes of dissected neonatal
      diaphragm, we found spreading of this dye into neighbouring cells. As expression
      of no other known connexin could be verified in these cells, intercellular dye
      transfer might result from functional expression of Cx39 in developing striated
      muscle fibers.

PMID- 15466893
TI  - Stable chromosomal units determine the spatial and temporal organization of DNA
      replication.
AB  - DNA replication occurs in mammalian cells at so-called replication foci occupying
      defined nuclear sites at specific times during S phase. It is an unresolved
      problem how this specific spatiotemporal organization of replication foci is
      determined. Another unresolved question remains as to what extent DNA is
      redistributed during S phase. To investigate these problems, we visualized the
      replicating DNA and the replication machinery simultaneously in living HeLa
      cells. Time-lapse analyses revealed that DNA was not redistributed to other
      nuclear sites during S phase. Furthermore, the results showed that DNA is
      organized into stable aggregates equivalent to replication foci. These
      aggregates, which we call sub-chromosomal foci, stably maintained their
      replication timing from S phase to S phase. During S-phase progression, the
      replication machinery sequentially proceeded through spatially adjacent sets of
      sub-chromosomal foci. These findings imply that the specific nuclear substructure
      of chromosomes and the order of their stable subunits determine the
      spatiotemporal organization of DNA replication.

PMID- 15466894
TI  - Relationship between growth hormone-IGF-I-IGFBP-3 axis and serum leptin levels
      with bone mass and body composition in patients with rheumatoid arthritis.
AB  - OBJECTIVES: Hormonal factors playing a role in bone mass and body composition
      have been rarely assessed in rheumatoid arthritis (RA). In this study, we aimed
      to evaluate the growth hormone (GH)-insulin-like growth factor-I (IGF-I)-insulin
      like growth factor binding protein-3 (IGFPB-3) axis and serum leptin levels in
      patients with RA and to determine whether these hormonal/growth factors may
      influence bone mass and body composition in RA. METHODS: Serum GH, IGF-I, IGFPB-3
      and leptin were evaluated in 38 corticosteroid-treated RA patients, 14 non-RA
      patients under corticosteroids (corticosteroid controls, CC) and 32 healthy
      controls (HC). Bone density was evaluated using dual X-ray absorptiometry (DEXA),
      and expressed as bone mineral density (BMD), and quantitative ultrasound (QUS).
      Body composition was assessed by DEXA. RESULTS: The three groups differed
      regarding femoral neck, total body BMD, lean mass and QUS parameters with lower
      values in the RA group (all P < or = 0.05). Growth hormone was higher in RA
      patients (P=0.0001) while IGF-I and IGFBP-3 did not differ between the three
      groups. In RA patients there was a tendency to high serum leptin levels and
      leptin strongly correlated with fat mass (r=0.83, P<0.0001), but not with bone
      mass measurements or inflammatory parameters. There were no differences for lean
      mass, GH and leptin between CC and HC. CONCLUSION: Our results suggest that these
      GH and leptin modifications could have an influence on both bone mass and body
      composition in RA.

PMID- 15466895
TI  - Localization of peptidylarginine deiminase 4 (PADI4) and citrullinated protein in
      synovial tissue of rheumatoid arthritis.
AB  - OBJECTIVES: Peptidylarginine deiminases (PADIs) convert peptidylarginine into
      citrulline via post-translational modification. Anti-citrullinated peptide
      antibodies are highly specific for rheumatoid arthritis (RA). Our genome-wide
      case-control study of single-nucleotide polymorphisms found that the PADI4 gene
      polymorphism is closely associated with RA. Here, we localized the expression of
      PADI4 and the citrullinated protein product in synovial RA tissue. METHODS: We
      used immunohistochemistry, double immunofluorescent labelling and western
      blotting. RESULTS: We found that PADI4 is extensively expressed in T cells, B
      cells, macrophages, neutrophils, fibroblast-like cells and endothelial cells in
      the lining and sublining areas of the RA synovium. We also found extracellular
      and intracellular expression of PADI4 in fibrin deposits with loose tissue
      structures where apoptosis was widespread. Unlike PADI4, citrullinated protein
      generally appeared in fibrin deposits that were abundant in the RA synovium. The
      citrullinated fibrin aggregate was immunoreactive against immunoglobulin (Ig) A
      and IgM, but not IgG and IgE. Although a little PADI4 was expressed in
      osteoarthritic and normal synovial tissues, significant citrullination was
      undetectable. CONCLUSIONS: The results showed that PADI4 is mainly distributed in
      cells of various haematopoietic lineages and expressed at high levels in the
      inflamed RA synovium. The co-localization of PADI4, citrullinated protein and
      apoptotic cells in fibrin deposits suggests that PADI4 is responsible for fibrin
      citrullination and is involved in apoptosis. The immunoreactivity of
      citrullinated fibrin with IgA and IgM in the RA synovium supports the notion that
      citrullinated fibrin is a potential antigen of RA autoimmunity.

PMID- 15466896
TI  - Nutritional impairment in juvenile idiopathic arthritis.
AB  - OBJECTIVE: To investigate the relationship between nutritional impairment,
      measured by body mass index (BMI), expressed as an age- and sex-standardized
      standard deviation score (BMI SDS), and disease and patient characteristics in a
      UK cohort of children with juvenile idiopathic arthritis (JIA). A subgroup with
      available dietary information were analysed separately. METHODS: Important
      disease and patient characteristics (age, gender, disease subtype, swollen joint
      count, painful joint count, restricted joint count, treatment and dietary
      assessment) were assessed as potential explanatory measures of BMI SDS in a
      multiple linear regression. RESULTS: Data were collected on 123 consecutive
      patients. Twenty were nutritionally impaired. In multiple regression analysis
      excluding the dietary data, disease subtype [persistent oligoarthritis and
      polyarthritis (rheumatoid factor-negative)], five or more joints with reduced
      range of movement and being younger were associated with lower BMI SDS (P<0.001).
      When energy and protein intake were included in the analysis for a subgroup of
      children, the resulting model retained only disease subtype as a predictor of a
      low BMI SDS (P = 0.013). CONCLUSIONS: In this unselected population of children
      with JIA, 16% had evidence of undernutrition. The most commonly affected subtype
      was oligoarthritis, a previously unreported finding. There is no evidence from
      this study that this nutritional impairment results from inadequate food intake
      and it is likely that it is multifactorial in aetiology, disease subtype being
      the most important factor.

PMID- 15466897
TI  - Pragmatic trials and the ARES study.

PMID- 15466898
TI  - Effects of CB1 cannabinoid receptor blockade on ethanol preference after chronic
      alcohol administration combined with repeated re-exposures and withdrawals.
AB  - AIMS: The cannabinoid CB1 receptor antagonist, SR141716A, differentially affects
      the ethanol preference of chronically alcoholized rats when administered during
      cycles of ethanol exposure and withdrawal. In this study, ethanol preference was
      investigated in chronically alcoholized rats that underwent regular withdrawal
      periods during which the brain cannabinoid CB(1) receptor antagonist, SR141716A,
      was administered. METHODS: The cannabinoid receptor antagonist SR141716A, 3 or 10
      mg/kg/day, was administered i.p. to Wistar rats at the conclusion of a 4-week
      period of chronic alcoholization, as they commenced a cycle of alcohol withdrawal
      for 10 days followed by a period of 10 days chronic ethanol exposure. In a second
      set of experiments, an additional cycle of ethanol withdrawal and re-exposure was
      given. Preference for ethanol versus water started at the end of the first or
      second chronic ethanol re-exposure for a period of at least 30 days. RESULTS: In
      rats pretreated with the higher dose of SR141716A, ethanol preference during free
      choice was significantly increased after two ethanol re-exposures. In contrast,
      pretreatment with the lower SR141716A dose induced no significant change in
      ethanol intake during the free choice followed by either one or two ethanol re
      exposures. CONCLUSIONS: SR141716A, 10 mg/kg/day dose, induced a significant
      increase in ethanol preference which was dependent on both the number of ethanol
      withdrawals and chronic ethanol re-exposures, while 3 mg/kg/day had no
      significant effect on ethanol preference.

PMID- 15466899
TI  - The addition of a psychological intervention to a home detoxification programme.
AB  - AIMS: Home detoxification is a recognized method of treating problem drinkers
      within their own home environment. The aim of this research is to determine
      whether a relatively brief psychological intervention adds to its effectiveness.
      METHODS: A pragmatic trial with 91 participants randomly assigned to either the
      psychological intervention or treatment as usual. Community Psychiatric Nurses
      were trained to administer the brief psychological intervention involving
      motivational interviewing, coping skills training and social support. A manual
      was developed in order to standardize the training and implementation. RESULTS:
      At the 3 month and 12 month follow-up the psychological intervention resulted in
      significant positive changes in alcohol consumption, abstinent days, social
      satisfaction, self-esteem and alcohol-related problems. Further, a cost analysis
      confirmed that the psychological intervention was a ninth of the cost of
      inpatient treatment. CONCLUSIONS: Adding a psychological intervention to a home
      detoxification programme was successful and cost-effective.

PMID- 15466903
TI  - Probable codeine phosphate-induced seizures.
AB  - OBJECTIVE: To report a case of seizure activity associated with oral codeine
      phosphate administered for analgesia in an elderly woman with end-stage renal
      disease. CASE SUMMARY: A 73-year-old Taiwanese woman with end-stage renal disease
      received oral codeine phosphate 30 mg 4 times daily for her back and rib pain
      without adjustment of her dosage regimen. Seven days after starting codeine
      therapy, the woman became stuporous and developed tonic-clonic seizures. After
      phenytoin initiation, codeine discontinuation, and naloxone administration, the
      seizures did not recur. DISCUSSION: Codeine is a frequently used opioid
      analgesic, especially when pain control with acetaminophen or nonsteroidal
      antiinflammatory drugs fails. Although seizures associated with codeine have been
      reported, pertinent data are very limited and the exact mechanism is unknown. An
      objective causality assessment indicated the seizure to be a probable drug
      related event in this patient. CONCLUSIONS: Elderly patients with end-stage renal
      disease may be predisposed to seizures with higher doses of codeine phosphate. It
      is imperative to adjust the codeine dosage regimen based on patients' renal
      function to avoid the potential toxicity with overdose.

PMID- 15466904
TI  - Probable vancomycin-induced neutropenia.
AB  - OBJECTIVE: To report a case of vancomycin-induced neutropenia and provide a
      review of the literature. CASE SUMMARY: A 64-year-old white man was treated with
      intravenous vancomycin 1.5 g/day for finger osteomyelitis. He developed
      neutropenia after 21 days of vancomycin therapy. The absolute neutrophil count
      reached a nadir of 418 cells/mm(3) during vancomycin use and returned to normal 7
      days after its discontinuation. The eosinophil count was also elevated during the
      neutropenic episode and probably related to vancomycin. Based on the Naranjo
      probability scale, the reaction was probably related to vancomycin use.
      DISCUSSION: Articles describing cases of vancomycin-induced neutropenia were
      identified. All patients developed neutropenia as a result of vancomycin therapy
      >/=12 days. Neutrophil counts generally increased following discontinuation of
      vancomycin. One article reported successful resolution of neutropenia and
      infection by switching the patient's therapy to the structurally related
      antibiotic agent teicoplanin. Other patients were continued on vancomycin
      therapy, and neutropenia was treated with moderate to good success with
      filgrastim. Rechallenge was not generally attempted. The mechanism of neutropenia
      caused by vancomycin is unclear, but appears to be immune-mediated. CONCLUSIONS:
      Vancomycin therapy should not be prolonged unless absolutely necessary, and
      therapy should be reserved for patients with clear indications for the drug, such
      as infections due to gram-positive organisms resistant to other therapies.
      Patients should have periodic assessment of white blood cell and neutrophil
      counts with consideration to discontinue vancomycin if neutropenia develops.

PMID- 15466905
TI  - Taste and smell disturbance with the alpha-adrenoceptor agonist midodrine.
AB  - OBJECTIVE: To report a case of a disturbance of taste and smell associated with
      the alpha-adrenoceptor agonist midodrine. CASE SUMMARY: A 64-year-old white man
      with autonomic failure was started on midodrine 5 mg/day as treatment for
      orthostatic hypotension. After 3 months, the dose was increased to 12.5 mg/day,
      whereupon he noted a new onset of taste and smell disturbance. These symptoms
      made eating so unpleasant that the man greatly reduced his food intake, leading
      to significant weight loss. In addition, he experienced well-recognized adverse
      effects of midodrine, such as scalp pruritus, after the dose increase. All
      symptoms resolved with a dose reduction of midodrine (to 5 mg/day), and the
      patient increased his food intake, resulting in a return to his initial body
      weight. DISCUSSION: Midodrine is commonly associated with dose-dependent adverse
      effects, such as scalp pruritus and cutis anserina. Disorders of taste and smell
      have not been previously reported with midodrine, although it has been suggested
      that other sympathomimetic drugs may have effects on the olfactory threshold.
      Severe disorders of taste and smell may impact not only on a patient's quality of
      life, but also on their physical well-being, with significant weight loss being
      reported in this case. According to the Naranjo probability scale, this patient's
      taste and smell disturbance was probably associated with midodrine. CONCLUSIONS:
      The use of midodrine may be associated with taste and smell disturbance. This
      case suggests that such an association is likely to be dose dependent.

PMID- 15466906
TI  - Attitudes of Finnish community pharmacists toward concordance.
AB  - BACKGROUND: Concordance is a new model of interaction between healthcare
      professionals and patients. The work of pharmacists and patients in the
      consultation is a negotiation between equals, and the aim is therapeutic alliance
      between them. OBJECTIVE: To assess Finnish community pharmacists' attitudes
      toward concordance and its perceived impact on pharmacist-patient consultations
      during a 4-year Finnish project (TIPPA Project 2000-2003) aimed at promoting
      patient counseling. METHODS: A survey of a random sample of 734 community
      pharmacists in Finland was conducted in 2002. The questionnaire included an
      attitudinal scale and 2 open-ended questions on the impact of the TIPPA Project
      on patient counseling. Attitudes toward concordance were measured using a
      modified version of the LATCon scale. The construct validity and internal
      consistency of the scale were evaluated using factor analysis and Cronbach's
      alpha. Mean summative factor scores (MSS) and 95% confidence intervals were
      calculated for each factor. The responses to the open-ended questions were
      content analyzed. RESULTS: A response rate of 51% (n = 376) was obtained. Almost
      80% of the respondents strongly agreed that the highest priority in patient
      counseling was to establish a therapeutic alliance between the pharmacist and
      patient. Factor analysis of the attitudinal scale yielded 3 primary factors
      explaining 37.6% of the variance, interpreted as respecting patients' beliefs
      (alpha = 0.60; MSS = 1.90; 95% CI 2.25 to 2.40), establishing a therapeutic
      alliance (alpha = 0.65; MSS = 1.36; 95% CI 1.31 to 1.40), and sensitivity to
      patients' reactions (alpha = 0.66; MSS = 2.33; 95% CI 1.83 to 1.96). Results of
      the open-ended questions indicated that the TIPPA Project had a positive impact
      on pharmacists' attitudes toward concordance. CONCLUSIONS: Respondents to our
      survey were supportive of concordance. The TIPPA Project elicited a positive
      impact on pharmacists' attitudes toward counseling. Pharmacist education through
      programs such as TIPPA can aid in the implementation of a concordance-based
      counseling practice.

PMID- 15466908
TI  - Comment: Trimethoprim/sulfamethoxazole for treatment of severe Staphylococcus
      aureus infections.

PMID- 15466909
TI  - TFExplorer: integrated analysis database for predicted transcription regulatory
      elements.
AB  - TFExplorer is a web-based integrated database for predicted regulatory elements
      in human, mouse and rat. It shows predicted binding sites of transcription
      factors in the promoter regions, along with their phylogenetic footprinting
      information. In addition, TFExplorer can search for genes that have a given
      sequence pattern in their promoter regions using the motif-searching method.
      AVAILABILITY: TFExplorer is freely available at
      http://mars.kribb.re.kr:8080/tfExplorer/ CONTACT: sskimb@kribb.re.kr.

PMID- 15466910
TI  - BagBoosting for tumor classification with gene expression data.
AB  - MOTIVATION: Microarray experiments are expected to contribute significantly to
      the progress in cancer treatment by enabling a precise and early diagnosis. They
      create a need for class prediction tools, which can deal with a large number of
      highly correlated input variables, perform feature selection and provide class
      probability estimates that serve as a quantification of the predictive
      uncertainty. A very promising solution is to combine the two ensemble schemes
      bagging and boosting to a novel algorithm called BagBoosting. RESULTS: When
      bagging is used as a module in boosting, the resulting classifier consistently
      improves the predictive performance and the probability estimates of both bagging
      and boosting on real and simulated gene expression data. This quasi-guaranteed
      improvement can be obtained by simply making a bigger computing effort. The
      advantageous predictive potential is also confirmed by comparing BagBoosting to
      several established class prediction tools for microarray data. AVAILABILITY:
      Software for the modified boosting algorithms, for benchmark studies and for the
      simulation of microarray data are available as an R package under GNU public
      license at http://stat.ethz.ch/~dettling/bagboost.html.

PMID- 15466911
TI  - Progression of spontaneous autoimmune diabetes is associated with a switch in the
      killing mechanism used by autoreactive CTL.
AB  - Autoimmune (type 1) diabetes mellitus results from the destruction of insulin
      producing pancreatic beta-cells by T lymphocytes. Beta-cell death that is induced
      by autoreactive CTL in diabetes involves both Fas/Fas ligand (FasL)- and
      perforin/granzyme-mediated pathways, although their relative contributions during
      the progression of the disease remain unknown. We demonstrate here that despite
      the preferential use of the Fas/FasL pathway for cytolysis of beta-cell targets,
      transgenic beta-cell-specific CTL were able to kill targets via the perforin
      pathway when triggered by a higher affinity stimulus. In addition, we show that
      the killing mechanism used by islet-associated CD8(+) T cells from non-obese
      diabetic mice changed as the mice aged and correspondingly, with the stage of
      diabetes. These results provide direct evidence for age-related changes in the
      cytotoxic pathways used by diabetogenic T cells during the progression of
      autoimmune diabetes.

PMID- 15466912
TI  - The p38 mitogen-activated protein kinase (MAPK) pathway mediates induction of the
      tissue factor gene in monocytes stimulated with human monoclonal anti
      beta2Glycoprotein I antibodies.
AB  - The anti-phospholipid syndrome (APS) is characterized by thrombosis and the
      presence of anti-phospholipid antibodies (aPL). Tissue factor (TF), the major
      initiator of the coagulation system, is induced on monocytes by aPL in vitro,
      explaining, in part, the pathophysiology in this syndrome. However, little is
      known regarding the nature of the aPL-induced signal transduction pathways
      leading to TF expression. In this study, we investigated aPL-inducible genes in
      PBMC using cDNA array system and real-time PCR. Our results indicated that the
      mitogen-activated protein kinase (MAPK) pathway was related to TF expression when
      PBMCs were treated, in the presence of beta(2)Glycoprotein I (beta(2)GPI), with
      human monoclonal anti-beta(2)GPI antibodies [beta(2)GPI-dependent anti
      cardiolipin antibodies (aCL/beta(2)GPI)]. Western blotting studies using monocyte
      cell line (RAW264.7) demonstrated that p38 MAPK protein was phosphorylated with
      nuclear factor kappaB (NF-kappaB) activation by monoclonal aCL/beta(2)GPI
      treatment, and that SB203580, a specific p38 MAPK inhibitor, decreased the
      aCL/beta(2)GPI-induced TF mRNA expression. The p38 MAPK phosphorylation, NF
      kappaB translocation and TF mRNA expression triggered by aCL/beta(2)GPI were
      abolished in the absence of beta(2)GPI. These results demonstrated that the p38
      MAPK signaling pathway plays an important role in aPL-induced TF expression on
      monocytes and suggest that the p38 MAPK may be a possible therapeutic target to
      modify a pro-thrombotic state in patients with APS.

PMID- 15466913
TI  - Bypassing luminal barriers, delivery to a gut addressin by parenteral targeting
      elicits local IgA responses.
AB  - Induction of mucosal immunity, particularly to subunit vaccines, has been
      problematic. The primary hurdle to successful mucosal vaccination is the
      effective delivery of vaccine antigen to the mucosal associated lymphoid tissue.
      Physical and chemical barriers restrict antigen access and, moreover, immune
      responses induced in the mucosa can be biased towards tolerance or non
      reactivity. We proposed that these difficulties could be circumvented by
      targeting antigen to the gastrointestinal associated lymphoid tissue via systemic
      (parenteral) rather than alimentary routes, using antibodies specific for the
      mucosal addressin cellular adhesion molecule-1 (MAdCAM). After intravenous or
      intramuscular injection of such rat antibodies in mice, we found a greatly
      enhanced (up to 3 logs) anti-rat antibody response. MAdCAM targeting induces a
      rapid IgA antibody response in the gut and vastly improves the systemic antibody
      response. Targeting also enhanced T cell proliferation and cytokine responses.
      Parenteral targeting of mucosal addressins may represent a generic technique for
      bypassing mucosal barriers and eliminating the need for adjuvants in the
      induction of proximal and systemic immunity.

PMID- 15466914
TI  - The contribution of Fc effector mechanisms in the efficacy of anti-CD154
      immunotherapy depends on the nature of the immune challenge.
AB  - Blockade of the CD154-CD40 co-stimulatory pathway with anti-CD154 mAbs has shown
      impressive efficacy in models of autoimmunity and allotransplantation. Clinical
      benefit was also demonstrated in systemic lupus erythematosus (SLE) and
      idiopathic thrombocytopenia patients with the humanized anti-CD154 mAb, 5C8
      (hu5C8). However, thromboembolic complications that occurred during the course of
      the hu5C8 clinical trials have proven to be a major setback to the field and safe
      alternative therapeutics targeting the CD154-CD40 pathway are of great interest.
      Recently, effector mechanisms have been shown to play a part in anti-CD154 mAb
      induced transplant acceptance in murine models, while this issue remains
      unresolved for humoral-mediated models. Herein, aglycosyl anti-CD154 mAbs with
      reduced binding to FcgammaR and complement were used as a novel means to test the
      role of effector mechanisms in non-human primate and murine models not amenable
      to gene knockout technology. While aglycosyl hu5C8 mAb was relatively ineffective
      in rhesus renal and islet allotransplantation, it inhibited primary and secondary
      humoral responses to a protein immunogen in cynomolgus monkeys. Moreover, an
      aglycosyl, chimeric MR1 mAb (muMR1) prolonged survival and inhibited pathogenic
      auto-antibody production in a murine model of SLE. Thus, the mechanisms required
      for efficacy of anti-CD154 mAbs depend on the nature of the immune challenge.

PMID- 15466915
TI  - The anti-inflammatory effects of a selectin ligand mimetic, TBC-1269, are not a
      result of competitive inhibition of leukocyte rolling in vivo.
AB  - Selectins and their ligands support leukocyte rolling, facilitating the
      subsequent firm adhesion and migration that occur during inflammation. TBC-1269
      (Bimosiamose), a structural mimetic of natural selectin ligands, inhibits P-, E-,
      and L-selectin in vitro, has anti-inflammatory effects in vivo, and recently
      underwent phase II clinical trials for childhood asthma and psoriasis. We studied
      whether the anti-inflammatory effects of TBC-1269 could be related to leukocyte
      rolling in vivo. Although TBC-1269 inhibited rolling of a murine leukocyte cell
      line on murine P-selectin in vitro and thioglycollate-induced peritonitis in
      vivo, it did not alter leukocyte rolling in mouse cremaster venules. TBC-1269
      reduced neutrophil recruitment in thioglycollate-induced peritonitis in wild-type
      and P-selectin-/- mice but not in E-selectin-/- mice. We suggest that the in vivo
      effects of TBC-1269 may be mediated through E-selectin but do not appear to
      involve leukocyte rolling.

PMID- 15466916
TI  - The coordination of signaling during Fc receptor-mediated phagocytosis.
AB  - Phagocytosis by macrophages can be initiated by Fcgamma receptors (FcR) in
      membranes that bind to Fc regions of immunoglobulin G (IgG). Activated FcR
      transduce signals to cytoplasm, which regulate the internalization of IgG-coated
      particles into plasma membrane-derived vacuoles, phagosomes. Particles
      internalized by phagocytosis are much larger than FcR, which prompts questions of
      if and how the receptors are coordinated with each other. FcR-mediated signal
      transduction entails recruitment of proteins from cytoplasm to the receptor,
      largely via protein phosphorylation. These FcR signaling complexes then activate
      proteins that regulate actin, myosin, membrane fusion, and the production of
      reactive oxygen intermediates. Recent fluorescence microscopic studies of
      phagocytosis in macrophages indicate that signaling by FcR occurs as a sequence
      of distinct stages, evident in the spatial and temporal patterns of
      phosphoinositides, protein kinase C, and Rho-family GTPase activation on forming
      phagosomes. The coordination of these stages may be regulated by lipids or lipid
      anchored proteins, which diffuse away from FcR complexes. Lateral diffusion of
      FcR-derived signals could integrate FcR-dependent responses over large areas of
      membrane in the forming phagosome.

PMID- 15466917
TI  - Atmospheric radon levels in Beijing, China.
AB  - The results of measurement of atmospheric radon concentration in Beijing, China,
      are reported. Continuous observation was performed hourly throughout 2003 to
      provide data on annual average radon concentration as well as the variation of
      radon concentration. An arithmetic annual mean value of 14.1 +/- 5.5 Bq m(-3) was
      obtained. The value was slightly higher than the world average and the national
      average. For the monthly average radon concentration, the maximum was 18.5 +/-
      5.0 Bq m(-3) in November, while the minimum was 9.9 +/- 4.1 Bq m(-3) in May.
      Diurnal variation was also observed, and the average daily pattern of radon
      concentration consisted of a minimum in the late afternoon and a maximum in the
      early hours of the morning.

PMID- 15466918
TI  - Thermoluminescence response of K2YF5:Tb3+ crystals to photon radiation fields.
AB  - This investigation has been performed to test the feasibility of using K2YF5:Tb3+
      crystals as thermoluminescence dosemeters (TLD). K2YF5 single crystals doped with
      0.2, 10.0 and 50.0 at.% of trivalent optically active Tb3+ ions as well as K2TbF5
      and undoped K2YF5 crystals have been synthesized under hydrothermal conditions.
      Polished crystal platelets with thickness of about 1 mm have been irradiated with
      X and gamma rays in order to study thermoluminescent (TL) sensitivity as well as
      dose and energy response in terms of the Tb3+ concentration in K2YF5. Within this
      concentration series, K2YF5 crystals doped with 10.0 at.% Tb3+ have been found to
      have maximum TL response due to a broad asymmetric TL glow peak at 269 degrees C
      with good linearity of dose response and reproducibility of dose measurements.
      After deconvolution, the main dosimetric peak has been revealed to be composed of
      two individual peaks, both with linear TL response behaviour, centered at 210 and
      269 degrees C. As it has been proved, the linear TL signal coefficient for
      K2Y0.9Tb0.1F5 is almost 10 times greater than that for commercial TLD-100
      (LiF:Mg,Ti), irradiated with a 137Cs gamma radiation source at the same
      conditions. The reported results indicate that K2YF5 crystals doped with Tb3+
      have potential as promising materials for radiation dosemeters.

PMID- 15466919
TI  - Long-term accumulation of uranium in bones of Wistar rats as a function of intake
      dosages.
AB  - Groups of Wistar rats were fed with ration doped with uranyl nitrate at
      concentration A ranging from 0.5 to 100 ppm, starting after the weaning period
      and lasting until the postpuberty period when the animals were sacrificed.
      Uranium in the ashes of bones was determined by neutron activation analysis. It
      was found that the uranium concentration in the bones, as a function of A,
      exhibits a change in its slope at approximately 20 ppm-a probable consequence of
      the malfunctioning of kidneys. The uranium transfer coefficient was obtained and
      an analytical expression was fitted into the data, thus allowing extrapolation
      down to low doses. Internal and localized doses were calculated. Absorbed doses
      exceeded the critical dose, even for the lowest uranium dosage.

PMID- 15466920
TI  - Lipid and fatty acid profiles in the brain, liver, and stomach contents of
      neonatal rats: effects of hypoxia.
AB  - Neonatal hypoxia leads to clinically significant fatty liver, presumably due to
      disturbances in lipid metabolism. To fully evaluate lipid metabolism, the present
      study analyzed the complete lipid profile of the brain, liver, and ingested
      stomach contents of 7-day-old rats exposed to hypoxia from birth. Hypoxia had
      negligible direct effects on lipid metabolism in the brain. Conversely, hypoxia
      exhibited direct effects on hepatic lipid metabolism that could not be fully
      explained by changes in dietary intake. Triacylglyceride concentration was
      significantly increased in the hypoxic liver but remained unchanged in the brain
      and stomach contents. Diacylglyceride concentration was increased in both the
      brain and liver, and this was associated with increased diacylglyceride in the
      stomach contents. Most n-3 and n-6 fatty acids were increased in the liver, but
      not in the brain, of hypoxic pups. These changes did not reflect those measured
      in the stomach contents. Saturated fatty acid concentrations were increased in
      both the hypoxic brain and liver, and these changes reflected those in the
      stomach contents. Hypoxia also increased total phospholipid concentration in the
      brain and stomach contents. We conclude that neonatal hypoxia indirectly affects
      specific lipid and fatty acid concentrations in the brain and liver through
      alterations in the absorbed stomach contents. Hypoxia also exhibits some direct
      affects through modulation of metabolic pathways in situ, mostly in the liver. In
      this respect, the neonatal brain exhibits tighter control on lipid homeostasis
      than the liver during neonatal hypoxia.

PMID- 15466921
TI  - Effects of endogenous estrogen on renal calcium and phosphate handling in elderly
      women.
AB  - High postmenopausal endogenous estrogen concentrations are an important
      determinant of preservation of bone mass and reduced fracture in elderly women.
      Calcium supplementation can also reduce bone loss in these patients, suggesting
      an interaction between estrogen deficiency and calcium balance. Potential
      mechanisms of estrogen on calcium transport include direct effects on the bone,
      the kidney, and the bowel. Previous studies have demonstrated effects of estrogen
      on renal phosphate handling. We have used a cross-sectional, population-based
      analysis of biochemical data obtained from ambulant elderly women to determine
      the association of endogenous estradiol with urine calcium and phosphorus
      excretion. The subjects were 293 postmenopausal women >70 yr old. Factors
      associated with renal calcium and phosphate excretion were measured, including
      the filtered calcium and phosphate load, parathyroid hormone (PTH), estradiol,
      and sex hormone-binding globulin (SHBG). The free estradiol concentration (FE)
      was calculated from a previously described formula. A high plasma estradiol
      concentration (r(2) = 0.023, P = 0.01) and a high FE (r(2) = 0.045, P = 0.001)
      were associated with reduced renal calcium excretion. The estradiol and FE effect
      on renal calcium excretion remained significant after adjusting for calcium
      filtered at the glomerulus and serum PTH. A high FE was associated with a reduced
      renal phosphate threshold in univariate analysis (r(2) = 0.023, P = 0.010). The
      effect remained significant after adjustment for serum PTH. The size of the
      effect of the FE was of the same order of magnitude as the effect of PTH on
      reducing renal calcium excretion and increasing renal phosphate excretion. These
      data support in vitro and animal data demonstrating an effect of estradiol on
      renal calcium and phosphate handling and indicate that, in elderly postmenopausal
      women, the effect is of a similar magnitude to the well-recognized effects of PTH
      on these physiologically regulated parameters.

PMID- 15466922
TI  - Macrophage activation syndrome: characteristic findings on liver biopsy
      illustrating the key role of activated, IFN-gamma-producing lymphocytes and IL-6-
      and TNF-alpha-producing macrophages.
AB  - Macrophage activation syndrome (MAS) is a rare and potentially fatal disorder,
      thought to result from uncontrolled activation and proliferation of T cells and
      excessive activation of macrophages. The term MAS designates a clinicopathologic
      entity that occurs in different hemophagocytic syndromes (HSs). Primary
      hemophagocytic lymphohistiocytosis (HLH) is recognized to have an immunogenetic
      basis, but in the secondary HS (also referred to as secondary HLH), the cause is
      unknown. The pathogenesis of the accelerated disease phase typical of MAS remains
      incompletely understood. This report describes the immunohistochemical findings
      on liver tissues from 5 children, each of whom presented with MAS in the context
      of a different type of HS. The data provide direct evidence for the involvement
      of activated CD8(+) lymphocytes through the production of interferon-gamma and of
      macrophages through hemophagocytosis and production of interleukin 6 and tumor
      necrosis factor-alpha, and underscore the view that MAS in different HSs share a
      common effector pathway.

PMID- 15466923
TI  - Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance
      engraftment in adults with hematologic malignancy.
AB  - Limited umbilical cord blood (UCB) cell dose compromises the outcome of adult UCB
      transplantation. Therefore, to augment graft cell dose, we evaluated the safety
      of the combined transplantation of 2 partially human leukocyte antigen (HLA)
      matched UCB units. Twenty-three patients with high-risk hematologic malignancy
      (median age, 24 years; range, 13-53 years) received 2 UCB units (median infused
      dose, 3.5 x 10(7) nucleated cell [NC]/kg; range, 1.1-6.3 x 10(7) NC/kg) after
      myeloablative conditioning. All evaluable patients (n = 21) engrafted at a median
      of 23 days (range, 15-41 days). At day 21, engraftment was derived from both
      donors in 24% of patients and a single donor in 76% of patients, with 1 unit
      predominating in all patients by day 100. Although neither nucleated or CD34(+)
      cell doses nor HLA-match predicted which unit would predominate, the
      predominating unit had a significantly higher CD3(+) dose (P < .01). Incidences
      of grades II-IV and III-IV acute GVHD were 65% (95% confidence interval [CI], 42%
      88%) and 13% (95% CI, 0%-26%), respectively. Disease-free survival was 57% (95%
      CI, 35%-79%) at 1 year, with 72% (95% CI, 49%-95%) of patients alive if they
      received transplants while in remission. Therefore, transplantation of 2
      partially HLA-matched UCB units is safe, and may overcome the cell-dose barrier
      that limits the use of UCB in many adults and adolescents.

PMID- 15466924
TI  - Geographic patterns and pathogenetic implications of IGHV gene usage in chronic
      lymphocytic leukemia: the lesson of the IGHV3-21 gene.
AB  - We studied immunoglobulin variable heavy-chain (IGHV) repertoire and mutational
      status in 553 patients with chronic lymphocytic leukemia (CLL) from the
      Mediterranean area to gain insight into the potential pathogenetic role of
      antigenic stimulation. The most commonly represented IGHV genes mirrored the
      usage of normal B cells, with the exception of IGHV1-18, IGHV3-30.3, and IGHV4-59
      that were underrepresented. The IGHV3-21 gene, frequently expressed in Northern
      European CLL, was present only in 16 cases (2.9%). Based on HCDR3 cluster
      analysis, cases using IGHV3-21 could be grouped in 2 subsets of similar
      frequency. The first one (7 of 16 cases) carried a similar HCDR3 amino acid
      sequence (common-HCDR3 subset), virtually identical to the Scandinavian IGHV3-21
      CLL. These cases used the IGHJ6 gene; 4 of 7 were unmutated; 6 of 7 carried the
      V(lambda)2-14 (IGLV3-21) light-chain gene with a similar LCDR3. All expressed
      CD38 and had a progressive disease. The second subset (9 of 16) was characterized
      by heterogeneous HCDR3 rearrangements (nonhomogeneous-HCDR3 subset), diverse IGHJ
      and IGV light-chain gene usage, variable IGHV mutational status (5 of 9
      unmutated), variable CD38 expression, and variable clinical course (4 of 9
      progressed). The first subset suggests a potential antigenic element rarely
      encountered in the Mediterranean area, possibly responsible for a negative
      outcome. The second subset may reflect the physiologic heterogeneity of
      expression of IGHV3-21 rearrangements in the normal repertoire and is
      characterized by a variable clinical outcome.

PMID- 15466925
TI  - A case for developing North-South partnerships for research in sickle cell
      disease.
AB  - For a better understanding of the pathophysiology and mechanisms of phenotypic
      diversity of sickle cell disease, and for the improvement of its management
      globally, there is a strong case for developing sustainable research partnerships
      between rich and poor countries.

PMID- 15466926
TI  - Cobalamin-responsive disorders in the ambulatory care setting: unreliability of
      cobalamin, methylmalonic acid, and homocysteine testing.
AB  - Early recognition of cobalamin (Cbl)-responsive disorders in the ambulatory care
      setting is essential to prevent irreversible neurologic deficits. However,
      diagnostic algorithms using Cbl, methylmalonic acid (MMA), and homocysteine
      (HCys) measurements reflect studies in academic centers, and their negative
      predictive values have not been established. Thus, records of 456 ambulatory
      patients evaluated for Cbl deficiency at a staff model HMO were reviewed.
      Pretherapy Cbl, MMA, and HCys values in individual patients varied by 23%, 23%,
      and 17%, respectively, over 2 to 6 weeks. Hematologic or neurologic responses to
      pharmacologic doses of Cbl occurred in 37 of the 95 evaluable patients. In these
      patients, pretherapy Cbl, MMA, and HCys values were normal in 54%, 23%, and 50%,
      respectively. If therapy had been restricted to symptomatic patients with both
      low or intermediate Cbl levels and increased metabolite values, 63% of responders
      would not have been treated. Twenty-five patients did not respond to treatment,
      including 5 of 11 patients (45%) with low Cbl, 22 of 49 patients (45%) with high
      MMA, and 13 of 30 patients (43%) with high HCys values. It is concluded that Cbl,
      MMA, and HCys levels fluctuate with time and neither predict nor preclude the
      presence of Cbl-responsive hematologic or neurologic disorders.

PMID- 15466927
TI  - The t-PA -7351C>T enhancer polymorphism decreases Sp1 and Sp3 protein binding
      affinity and transcriptional responsiveness to retinoic acid.
AB  - We have previously identified a common polymorphism at the tissue-type
      plasminogen activator (t-PA) locus (-7351C>T), located within a GC-box in the
      retinoic acid (RA) and steroid hormone responsive t-PA enhancer. The aim of the
      present study was to functionally characterize this t-PA variant. Electrophoretic
      mobility shift assays (EMSAs) using crude nuclear extracts from human
      endothelial, HeLa, and NT2 neuronal cells revealed a 10-fold greater protein
      binding affinity to the wild-type C allele compared with the mutant T allele
      variant. Sp1 and Sp3 were identified as the GC-box binding proteins. Luciferase
      reporter assays showed that the C allele generated higher transcriptional
      activity after induction by RA, compared with the T allele variant. Further EMSAs
      showed that RA treatment enhanced Sp1/Sp3 binding to the GC-box. Formation of the
      Sp1/Sp3 containing complex was inhibited by anti-RA receptor (RAR) antibodies,
      suggesting that Sp1/Sp3 and RAR interact. The t-PA -7351C>T polymorphism is
      therefore functional at the level of transcription. The reduced binding affinity
      of Sp1/Sp3 to the T allele could explain our earlier observations of a reduced t
      PA release and an increased risk of myocardial infarction in individuals carrying
      this allele.

PMID- 15466928
TI  - HLA-G expression is associated with an unfavorable outcome and immunodeficiency
      in chronic lymphocytic leukemia.
AB  - The human leukocyte antigen G (HLA-G) molecule exhibits limited tissue
      distribution and exerts multiple immunoregulatory functions. Recent studies
      indicate an ectopic up-regulation in tumor cells that may favor their escape from
      antitumor immune responses. The role of HLA-G in B-cell chronic lymphocytic
      leukemia (B-CLL) has not been defined. HLA-G expression was studied
      retrospectively in circulating B-CLL cells from 47 patients by flow cytometry
      using the anti-HLA-E specific monoclonal antibody MEM/G9. The proportion of
      leukemic cells expressing HLA-G varied from 1% to 54%. Patients with 23% or fewer
      HLA-G-positive cells (according to receiver operating characteristics [ROC]
      analysis; designated as HLA-G-negative group) had a significantly longer
      progression-free survival (PFS) time than patients with more than 23% positive
      cells (median PFS: 120 versus 23 months; P = .0001). In multivariate analysis,
      HLA-G expression (hazard ratio: 4.8; P = .002) was an even better independent
      prognostic factor than the zeta-associated protein 70 (ZAP-70) or CD38 status.
      Humoral and cellular immunosuppression were significantly more prominent in the
      HLA-G-positive compared with the HLA-G-negative patient group. In B-CLL, the
      level of HLA-G expression is correlated with the degree of immunosuppression and
      prognosis. HLA-G may contribute to the impairment of immune responses against
      tumor cells and infections. Thus, these findings need to be confirmed in a
      prospective study.

PMID- 15466929
TI  - Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis.
AB  - The role of the fibrinolytic system in the development of deep vein thrombosis
      (DVT) is unclear. We determined the plasma fibrinolytic potential of patients
      enrolled in the Leiden Thrombophilia Study (LETS), a population-based case
      control study on risk factors for DVT. Plasma fibrinolytic potential was
      determined in 421 patients and 469 control subjects by means of a tissue factor
      induced and tissue-type plasminogen activator (tPA)-induced clot lysis assay.
      Using clot lysis times above the 70th, 80th, 90th, 95th, and 99th percentiles of
      the values found in control subjects as cut-off levels, we found a dose-dependent
      increase in risk for DVT in patients with hypofibrinolysis (odds ratios of 1.4,
      1.6, 1.9, 2.1, and 2.2, respectively). This indicates a 2-fold increased risk of
      DVT in subjects with clot lysis times above the 90th percentile. The risk
      increase was not affected by age or sex (adjusted odds ratio for 90th percentile,
      2.0), and after correction for all possible confounders (age, sex, and levels of
      procoagulant proteins shown to associate with clot lysis times in the control
      population), the risk estimate was marginally reduced (odds ratio, 1.6 for 90th
      percentile). Taken together, these results indicate that plasma hypofibrinolysis
      constitutes a risk factor for venous thrombosis, with a doubling of the risk at
      clot lysis times that are present in 10% of the population.

PMID- 15466930
TI  - Both perforin and Fas ligand are required for the regulation of alloreactive CD8+
      T cells during acute graft-versus-host disease.
AB  - Fas ligand (FasL) and perforin pathways not only are the major mechanisms of T
      cell-mediated cytotoxicity but also are involved in homeostatic regulation of
      these T cells. In the present study, we tested whether CD8+ donor T cells that
      are deficient in both perforin and FasL (cytotoxic double deficient [cdd]) could
      induce graft-versus-host disease (GVHD) in a major histocompatibility complex
      class I-mismatched lethally irradiated murine model. Interestingly, recipients of
      cdd CD8+ T cells demonstrated significantly greater serum levels of interferon
      gamma and tumor necrosis factor alpha and histopathologic damage from GVHD than
      wild-type (wt) T cells on day 30 after allogeneic bone marrow transplantation
      (P<.05). Wt and either perforin-deficient or FasL-deficient CD8+ T cells expanded
      early after transplantation followed by a contraction phase in which the majority
      of expanded CD8+ T cells were eliminated. In contrast, cdd CD8+ T cells exhibited
      prolonged expansion and reduced apoptosis to alloantigen stimulation in vivo and
      in vitro. Together these results suggest that donor cdd CD8+ T cells expand
      continuously and cause lethal GVHD, and that both perforin and FasL are required
      for the contraction of allo-reactive CD8+ T cells.

PMID- 15466931
TI  - A novel apoptosis pathway activated by the carboxyl terminus of p21.
AB  - Delivery of biologically active peptides into cells may help elucidate
      intracellular signal transduction pathways, identify additional in vivo
      functions, and develop new therapeutics. Although p21 was first identified as a
      major regulator of cell cycle progression, it is now clear that p21 subserves
      multiple functions. The amino terminus of p21 interacts with cyclins and cyclin
      dependent kinases, while the carboxyl terminus interacts with proliferating cell
      nuclear antigen (PCNA), growth arrest and DNA damage-inducible gene 45 (GADD45),
      calmodulin, SET, and CCAAT/enhancer binding protein-alpha (C/EBP-alpha). A
      chimeric peptide, p21-IRS, consisting of the carboxyl terminal domain of p21
      conjugated to a pentapeptide (RYIRS) rapidly enters lymphoid cells and activates
      apoptosis. In the present study, we investigate the molecular events involved in
      p21-activated apoptosis. Comparison of p21-IRS with other known proapoptotic
      agents demonstrates that p21-IRS activates a novel apoptotic pathway:
      mitochondria are central to the process, but caspases and a decrease in
      Deltapsi(m) are not involved. Targeting the p21 peptide to specific cell
      populations may allow development of novel therapies to eliminate aberrant cells
      in human diseases.

PMID- 15466932
TI  - Regulation of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA-synthetase by
      CTLA-4-Fc in human CD4+ T cells.
AB  - Indoleamine-2,3-dioxygenase (IDO) and tryptophanyl-tRNA-synthetase (TTS) are
      interferon-gamma (IFN-gamma)-inducible enzymes that are responsible for
      tryptophan degradation and for its use in protein synthesis, respectively. IFN
      gamma-induced IDO has immunomodulatory properties in murine and human models. A
      concomitant increase of TTS has been postulated to protect the IDO-expressing
      cells from tryptophan catabolism. IDO can be induced in dendritic cells (DCs) by
      recombinant soluble cytotoxic T lymphocyte antigen-4 (CTLA-4-Fc). We investigated
      the effects of CTLA-4-Fc on IDO and TTS mRNA expression in human peripheral blood
      mononuclear cells (PBMCs) and isolated leukocyte subsets. CTLA-4-Fc exposure
      induced increased IDO and TTS expression in unseparated PBMCs, as well as in
      monocyte-derived mature DCs. CD4(+) T cells isolated from CTLA-4-Fc-treated PBMCs
      showed increased IDO and TTS compared with untreated cells. CD8(+) T cells from
      CTLA-4-Fc-treated PBMCs expressed increased levels of TTS but not IDO.
      Pretreatment of PBMCs with CTLA-4-Fc inhibited the activation of CD4(+) T cells
      induced by influenza A virus (Flu) or phytohemagglutinin A (PHA), but had no
      effect on CD8(+) T cells. This is the first report of IDO and TTS regulation by
      the CTLA-4-B7 system in human CD4(+) and CD8(+) T cells, and raises the
      possibility that these 2 tryptophan-modulating enzymes provide an important
      mechanism for regulating immune responses.

PMID- 15466933
TI  - Trolox selectively enhances arsenic-mediated oxidative stress and apoptosis in
      APL and other malignant cell lines.
AB  - Although arsenic trioxide (As(2)O(3)) is an effective therapy in acute
      promyelocytic leukemia (APL), its use in other malignancies is limited by the
      toxicity of concentrations required to induce apoptosis in non-APL tumor cells.
      We looked for agents that would synergize with As(2)O(3) to induce apoptosis in
      malignant cells, but not in normal cells. We found that trolox (6-hydroxy-2,5,7,8
      tetramethylchroman-2-carboxylic acid), a widely known antioxidant, enhances
      As(2)O(3)-mediated apoptosis in APL, myeloma, and breast cancer cells. Treatment
      with As(2)O(3) and trolox increased intracellular oxidative stress, as evidenced
      by heme oxygenase-1 (HO-1) protein levels, c-Jun terminal kinase (JNK)
      activation, and protein and lipid oxidation. The synergistic effects of trolox
      may be specific to As(2)O(3), as trolox does not add to toxicity induced by other
      chemotherapeutic drugs. We explored the mechanism of this synergy using electron
      paramagnetic resonance and observed the formation of trolox radicals when trolox
      was combined with As(2)O(3), but not with doxorubicin. Importantly, trolox
      protected nonmalignant cells from As(2)O(3)-mediated cytotoxicity. Our data
      provide the first evidence that trolox may extend the therapeutic spectrum of
      As(2)O(3). Furthermore, the combination of As(2)O(3) and trolox shows potential
      specificity for tumor cells, suggesting it may not increase the toxicity
      associated with As(2)O(3) monotherapy in vivo.

PMID- 15466934
TI  - A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic
      lymphocytic leukemia and acute myeloid leukemia.
AB  - Preclinical studies with the histone deacetylase (HDAC) inhibitor depsipeptide
      (FK228) in chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML)
      have demonstrated that it effectively induces apoptosis at concentrations at
      which HDAC inhibition occurs. We initiated a minimum effective pharmacologic dose
      study of depsipeptide, targeting an in vivo dose at which acetylation of histone
      proteins H3 and H4 increased by 100% or more in vitro. Ten patients with CLL and
      10 patients with AML were treated with 13 mg/m(2) depsipeptide intravenously days
      1, 8, and 15 of therapy. Neither life-threatening toxicities nor cardiac
      toxicities were noted, although the majority of patients experienced progressive
      fatigue, nausea, and other constitutional symptoms that prevented repeated
      dosing. Several patients had evidence of antitumor activity following treatment,
      but no partial or complete responses were noted by National Cancer Institute
      criteria. HDAC inhibition and histone acetylation increases of at least 100% were
      noted, as well as increases in p21 promoter H4 acetylation, p21 protein, and 1D10
      antigen expression. We conclude that depsipeptide effectively inhibits HDAC in
      vivo in patients with CLL and AML, but its use in the current schedule of
      administration is limited by progressive constitutional symptoms. Future studies
      with depsipeptide should examine alternative administration schedules.

PMID- 15466935
TI  - Endostatin dramatically inhibits endothelial cell migration, vascular
      morphogenesis, and perivascular cell recruitment in vivo.
AB  - Endostatin is a proteolytic fragment of collagen XVIII that inhibits endothelial
      cell migration in vitro and experimental tumor growth in vivo. To determine how
      endostatin affects the in vivo behavior of endothelial cells, we took advantage
      of a surrogate model of human angiogenesis, in which human endothelial cells are
      transferred to immunodeficient mice and develop into complex vessels in the
      course of 30 days. Systemic delivery of human yeast-derived endostatin (serum
      levels of 30-35 ng/mL) inhibited the number of human vessels dramatically (95% at
      day 20), as most endothelial cells remained suspended as single cells. The
      fraction of cells with a migratory phenotype (F-actin-positive, extending
      pseudopods) was strongly reduced (from 50% to 13% at day 10), while the number of
      apoptotic and mitotic cells remained unchanged. Endostatin also hampered the
      recruitment of alpha-smooth muscle actin-expressing perivascular cells and thus
      reduced the number of mature vessels (from 64.3% to 28.6% at day 30). Moreover,
      transcripts of pericyte-recruiting platelet-derived growth factor-B (PDGFB) were
      strongly reduced in endothelial cells of endostatin-treated mice. Our results are
      strong evidence that endostatin inhibits angiogenesis at several levels in vivo,
      including perivascular cell recruitment.

PMID- 15466936
TI  - A role for the thiol isomerase protein ERP5 in platelet function.
AB  - Formation and rearrangement of disulfide bonds during the correct folding of
      nascent proteins is modulated by a family of enzymes known as thiol isomerases,
      which include protein disulfide isomerase (PDI), endoplasmic reticulum protein 5
      (ERP5), and ERP57. Recent evidence supports an alternative role for this family
      of proteins on the surface of cells, where they are involved in receptor
      remodeling and recognition. In platelets, blocking PDI with inhibitory antibodies
      inhibits a number of platelet activation pathways, including aggregation,
      secretion, and fibrinogen binding. Analysis of human platelet membrane fractions
      identified the presence of the thiol isomerase protein ERP5. Further study showed
      that ERP5 is resident mainly on platelet intracellular membranes, although it is
      rapidly recruited to the cell surface in response to a range of platelet
      agonists. Blocking cell-surface ERP5 using inhibitory antibodies leads to a
      decrease in platelet aggregation in response to agonists, and a decrease in
      fibrinogen binding and P-selectin exposure. It is possible that this is based on
      the disruption of integrin function, as we observed that ERP5 becomes physically
      associated with the integrin beta(3) subunit during platelet stimulation. These
      results provide new insights into the involvement of thiol isomerases and
      regulation of platelet activation.

PMID- 15466938
TI  - Estrogen regulation of growth hormone action.
AB  - GH plays a pivotal role in regulating body growth and development, which is
      modulated by sex steroids. A close interplay between estrogen and GH leads to
      attainment of gender-specific body composition during puberty. The physiological
      basis of the interaction is not well understood. Most previous studies have
      focused on the effects of estrogen on GH secretion. There is also strong evidence
      that estrogen modulates GH action independent of secretion. Oral but not
      transdermal administration of estrogen impairs the metabolic action of GH in the
      liver, causing a fall in IGF-I production and fat oxidation. This results in a
      loss of lean tissue and a gain of body fat in postmenopausal women and an
      impairment of GH effect in hypopituitary women on GH replacement. The negative
      metabolic sequelae are potentially important because of the widespread use of
      oral estrogen and estrogen-related compounds. Estrogen affects GH action at the
      level of receptor expression and signaling. More recently, estrogen has been
      shown to inhibit Janus kinase/signal transducer and activator of transcription
      signaling by GH via the induction of suppressor of cytokine signaling-2, a
      protein inhibitor for cytokine signaling. This represents a novel paradigm of
      steroid regulation of cytokine receptors and is likely to have significance for a
      diverse range of cytokine function.

PMID- 15466939
TI  - Thyroid development and its disorders: genetics and molecular mechanisms.
AB  - Thyroid gland organogenesis results in an organ the shape, size, and position of
      which are largely conserved among adult individuals of the same species, thus
      suggesting that genetic factors must be involved in controlling these parameters.
      In humans, the organogenesis of the thyroid gland is often disturbed, leading to
      a variety of conditions, such as agenesis, ectopy, and hypoplasia, which are
      collectively called thyroid dysgenesis (TD). The molecular mechanisms leading to
      TD are largely unknown. Studies in murine models and in a few patients with
      dysgenesis revealed that mutations in regulatory genes expressed in the
      developing thyroid are responsible for this condition, thus showing that TD can
      be a genetic and inheritable disease. These studies open the way to a novel
      working hypothesis on the molecular and genetic basis of this frequent human
      condition and render the thyroid an important model in the understanding of
      molecular mechanisms regulating the size, shape, and position of organs.

PMID- 15466940
TI  - Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ
      cell movement in the seminiferous epithelium during spermatogenesis.
AB  - Spermatogenesis is the process by which a single spermatogonium develops into 256
      spermatozoa, one of which will fertilize the ovum. Since the 1950s when the
      stages of the epithelial cycle were first described, reproductive biologists have
      been in pursuit of one question: How can a spermatogonium traverse the
      epithelium, while at the same time differentiating into elongate spermatids that
      remain attached to the Sertoli cell throughout their development? Although it was
      generally agreed upon that junction restructuring was involved, at that time the
      types of junctions present in the testis were not even discerned. Today, it is
      known that tight, anchoring, and gap junctions are found in the testis. The
      testis also has two unique anchoring junction types, the ectoplasmic
      specialization and tubulobulbar complex. However, attention has recently shifted
      on identifying the regulatory molecules that "open" and "close" junctions,
      because this information will be useful in elucidating the mechanism of germ cell
      movement. For instance, cytokines have been shown to induce Sertoli cell tight
      junction disassembly by shutting down the production of tight junction proteins.
      Other factors such as proteases, protease inhibitors, GTPases, kinases, and
      phosphatases also come into play. In this review, we focus on this cellular
      phenomenon, recapping recent developments in the field.

PMID- 15466941
TI  - The cellular fate of glucose and its relevance in type 2 diabetes.
AB  - Type 2 diabetes is a complex disorder with diminished insulin secretion and
      insulin action contributing to the hyperglycemia and wide range of metabolic
      defects that underlie the disease. The contribution of glucose metabolic pathways
      per se in the pathogenesis of the disease remains unclear. The cellular fate of
      glucose begins with glucose transport and phosphorylation. Subsequent pathways of
      glucose utilization include aerobic and anaerobic glycolysis, glycogen formation,
      and conversion to other intermediates in the hexose phosphate or hexosamine
      biosynthesis pathways. Abnormalities in each pathway may occur in diabetic
      subjects; however, it is unclear whether perturbations in these may lead to
      diabetes or are a consequence of the multiple metabolic abnormalities found in
      the disease. This review is focused on the cellular fate of glucose and relevance
      to human type 2 diabetes.

PMID- 15466942
TI  - 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of
      glucocorticoid response.
AB  - 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) interconverts inactive
      cortisone and active cortisol. Although bidirectional, in vivo it is believed to
      function as a reductase generating active glucocorticoid at a prereceptor level,
      enhancing glucocorticoid receptor activation. In this review, we discuss both the
      genetic and enzymatic characterization of 11beta-HSD1, as well as describing its
      role in physiology and pathology in a tissue-specific manner. The molecular basis
      of cortisone reductase deficiency, the putative "11beta-HSD1 knockout state" in
      humans, has been defined and is caused by intronic mutations in HSD11B1 that
      decrease gene transcription together with mutations in hexose-6-phosphate
      dehydrogenase, an endoluminal enzyme that provides reduced nicotinamide-adenine
      dinucleotide phosphate as cofactor to 11beta-HSD1 to permit reductase activity.
      We speculate that hexose-6-phosphate dehydrogenase activity and therefore reduced
      nicotinamide-adenine dinucleotide phosphate supply may be crucial in determining
      the directionality of 11beta-HSD1 activity. Therapeutic inhibition of 11beta-HSD1
      reductase activity in patients with obesity and the metabolic syndrome, as well
      as in glaucoma and osteoporosis, remains an exciting prospect.

PMID- 15466943
TI  - The effects of high protein diets on thermogenesis, satiety and weight loss: a
      critical review.
AB  - For years, proponents of some fad diets have claimed that higher amounts of
      protein facilitate weight loss. Only in recent years have studies begun to
      examine the effects of high protein diets on energy expenditure, subsequent
      energy intake and weight loss as compared to lower protein diets. In this study,
      we conducted a systematic review of randomized investigations on the effects of
      high protein diets on dietary thermogenesis, satiety, body weight and fat loss.
      There is convincing evidence that a higher protein intake increases thermogenesis
      and satiety compared to diets of lower protein content. The weight of evidence
      also suggests that high protein meals lead to a reduced subsequent energy intake.
      Some evidence suggests that diets higher in protein result in an increased weight
      loss and fat loss as compared to diets lower in protein, but findings have not
      been consistent. In dietary practice, it may be beneficial to partially replace
      refined carbohydrate with protein sources that are low in saturated fat. Although
      recent evidence supports potential benefit, rigorous longer-term studies are
      needed to investigate the effects of high protein diets on weight loss and weight
      maintenance.

PMID- 15466944
TI  - Hyperhomocysteinemia, enzyme polymorphism and thiobarbituric Acid reactive system
      in children with high coronary risk family history.
AB  - OBJECTIVES: To investigate both the frequency and the genetic background of
      hyperhomocysteinemia and the frequency of increased plasma thiobarbituric acid
      reactive system (TBARS) levels in children and adolescents whose parents had
      premature coronary heart disease (CHD). METHODS: The study was performed on
      children and adolescents aged 4-18 years (105 offspring of parents with CHD
      before age 45 and 74 referents from families without any evidence of premature
      atherosclerosis). Fasting serum total cholesterol (TC), high density lipoprotein
      cholesterol (HDL-C), and total triglyceride (TG) levels were measured by
      enzymatic methods. Low density lipoprotein cholesterol (LDL-C) level was
      calculated by the Friedewald formula. Plasma total homocysteine (THCy) level was
      measured by fluorescence polarisation immunoassay. Plasma TBARS level was
      determined by fluorimetric method. 5,10-methylenetetrahydrofolate reductase
      (MTHFR) enzyme polymorphism was analyzed by polymerase chain reaction with
      restriction fragment length polymorphism (PCR-RFLP). RESULTS:
      Hyperhomocysteinemia was found in 32 cases and in 4 controls. Increased plasma
      THCy level was found in 10 children and adolescents from 12 cases homozygous for
      the C677T polymorphism of the MTHFR gene. No similar high frequency was observed
      in heterozygous subjects. Elevated fasting plasma TBARS levels were found in 38
      cases and in 8 controls. The frequency differences were significant (p < 0.01).
      Allele frequency of the MTHFR polymorphism among cases and controls was similar.
      Significant correlation (r = 0.53, p < 0.02) was detected between plasma THCy and
      TBARS levels. One child had high serum TC level, 5 had low serum HDL-C level and
      all other children had normal serum TC, LDL-C, HDL-C and TG levels from children
      with hyperhomocysteinemia and/or high plasma TBARS levels. A significant
      correlation (r = 0.64, p < 0.01) was observed between plasma THCy levels of
      parents and children in the case group. CONCLUSION: The measurement of plasma
      THCy and TBARS levels may contribute to the detection of the risk of children and
      adolescents with high CHD risk family history.

PMID- 15466945
TI  - Weight control measures among university students in a developing country: a
      cultural association or a risk behavior.
AB  - OBJECTIVE: The purpose of the study was to determine the prevalence of university
      students, in Lebanon, trying to lose weight and assess the relation of trying to
      lose weight with demographic, scholastic and health behavioral factors. METHODS:
      The study was cross-sectional conducted in the academic year 2000-2001. A
      proportionate random sample of 2,013 students was selected among five public and
      private universities in Beirut. Participants completed a self-administered
      anonymous questionnaire that included questions on trying to lose weight,
      demographic, scholastic, and health behavioral factors including smoking,
      alcohol, and seat belt use. Bivariate and stepwise logistic regression analyses
      were performed to examine the association between trying to lose weight and the
      above-mentioned characteristics. RESULTS: The overall prevalence of students
      trying to lose weight was 30%, with 71% of them being under weight or normal
      weight. Use of medications and inducement of vomiting constituted 12% and 11%,
      respectively. Stepwise logistic regression analysis showed that the variables
      significantly associated with trying to lose weight were socio-economical factors
      rather than risky behaviors. Students who were at increased odds of performing
      such methods were females OR = (2.08, 95% CI = 1.6-2.5), employed (OR = 1.36, 95%
      CI = 1.01-1.8), and registered in a private university (OR = 1.69, 95% CI = 1.25
      2.0). The major of students was also a significant predictor. CONCLUSION: In
      Lebanon, weight reduction could be re-enforced by socio-economical factors and
      not necessarily be an adolescent risk behavior.

PMID- 15466946
TI  - Oats, antioxidants and endothelial function in overweight, dyslipidemic adults.
AB  - OBJECTIVE: To determine effects of oat and antioxidant vitamin (C 500 mg, E 400
      IU) ingestion on endothelial function in overweight, dyslipidemic adults. DESIGN:
      Randomized, blinded, placebo-controlled, crossover trial Intervention(s):
      Subjects (16 males > or = age 35; 14 postmenopausal females) were assigned, in
      random order, to oats (60 g oatmeal), vitamin E (400 IU) plus vitamin C (500 mg),
      the combination of oats and vitamins, or placebo, and underwent brachial artery
      reactivity scans (BARS) following a single dose of each treatment, and again
      following 6 weeks of daily ingestion, with 2-week washout periods. At each test,
      a provocation high-fat meal (50 g, predominantly saturated) was administered and
      subjects were scanned pre, and 3 hours post-ingestion. RESULTS: Mean flow
      mediated vasodilation (FMD; measured as percent diameter change before and after
      treatments) at baseline was 6.35 +/- 3.37. Oats increased FMD non-significantly
      (p > 0.05) with both single acute dose (from 6.07 +/- 6.25 to 9.22 +/- 8.82) and
      six weeks of sustained treatment (from 6.01 +/- 10.07 to 8.69 +/- 8.42). The
      direction of effect was negative for vitamins and the oat/vitamin combination
      with both acute and sustained treatment. There were no significant differences in
      FMD change among the treatments in either phase of the study, however when acute
      and sustained effects were pooled, oat treatment significantly augmented FMD (p <
      0.05). CONCLUSIONS: This trial suggests but does not confirm a beneficial
      influence of oat ingestion on endothelial function in overweight, dyslipidemic
      adults. Further study of this potential association is warranted.

PMID- 15466947
TI  - Associations between food variety and body fatness in Hong Kong Chinese adults.
AB  - BACKGROUND: Food variety is reported to be closely associated with body fatness
      in Caucasians. The association has not been examined in a Chinese population.
      OBJECTIVE: To examine the association between food variety and body fatness in
      Hong Kong Chinese adults. DESIGN: One hundred and twenty Hong Kong Chinese adults
      (aged 18-50 y). Usual dietary intake over a one-week period of all subjects was
      assessed by using a food frequency questionnaire. Anthropometric parameters were
      measured using standardized methods. RESULTS: Varieties of grain and meat were
      negatively correlated with obesity indices (grain vs. BMI/body fat/waist/hip
      circumferences: partial r = -47/-0.43/-0.46/-0.42, p < 0.001; meat vs. BMI/body
      fat/waist/hip circumferences: partial r = -0.31/-0.24/-0.25/-0.29, p < 0.01). In
      contrast, there was a positive relationship between variety of snack and obesity
      indices (snack vs. BMI/body fat/waist/hip circumferences: partial r =
      0.35/0.42/0.42/0.36, p < 0.001). A food variety ratio derived from varieties of
      snack, grain and meat, was a stronger predictor of body fat compared with dietary
      fat in a regression model. CONCLUSION: Food variety may contribute to the local
      escalation in the prevalence of obesity. The variety of snack is the promoting
      factor for obesity while the variety of grains and meats may counteract its
      development. The findings of this study may have implications for treatment of
      obesity and the prevention of further weight gain.

PMID- 15466948
TI  - Plasma D-glucose, D-fructose and insulin responses after oral administration of D
      glucose, D-fructose and sucrose to normal rats.
AB  - OBJECTIVE: To assess whether oral D-fructose modifies the plasma D-glucose and
      insulin responses to oral D-glucose administration in normal rats. DESIGN: Oral D
      glucose (1.7, 3.5, 6.9 or 13.9 micromol/g body weight), D-fructose (6.9
      micromol/g), both D-glucose and D-fructose (1.7 or 3.5 micromol/g of each hexose)
      or sucrose (3.7 micromol/g) were administered intragastrically to overnight
      fasted rats and the plasma concentration of D-glucose, D-fructose and insulin
      measured over the ensuing 120 minutes. Control experiments were conducted after
      oral administration of H(2)O or saline. RESULTS: The administration of D
      fructose, given as the free hexose or as sucrose, instead of augmenting the
      plasma D-glucose concentration evoked by the concomitant administration of D
      glucose, tended both to improve the insulin response of the pancreatic B-cell and
      to minimize hyperglycemia, when compared to the results of experiments including
      the administration of equimolar amounts of D-glucose alone. For instance, the
      area under the plasma D-glucose curve was comparable in the rats receiving both D
      glucose and D-fructose (3.5 micromol/g of each hexose) and the rats receiving
      only D-glucose (3.5 micromol/g), averaging respectively 836 +/- 32 and 850 +/- 34
      mM . min each. Likewise, the paired ratio between the areas under the plasma
      insulin and D-glucose curves, when corrected for the threshold concentration for
      the insulinotropic action of the hexose (2.05 +/- 0.10 mM), averaged 44.3 +/- 3.0
      nmol/mol in the 16 rats receiving D-fructose alone, sucrose alone or both D
      glucose and D-fructose, as compared to 37.7 +/- 2.9 nmol/mol in the 22 rats
      receiving increasing amounts of D-glucose alone. CONCLUSIONS: The intake of D
      fructose, as the free hexose or as sucrose, favours D-glucose homeostasis. This
      is likely to be attributable to the reciprocal effects of the aldose and ketose
      upon their respective phosphorylation by glucokinase in both hepatocytes and
      insulin-producing pancreatic islet cells.

PMID- 15466949
TI  - Benefits and risks of sex hormone replacement in postmenopausal women.
AB  - Because cardiovascular disease (CVD), which is far less common in young women
      than in men, but increases in prevalence in the postmenopausal years to that of
      men, estrogen repletion therapy (ERT) or combined hormone replacement therapy
      (HRT), has been widely used to protect against development of both CVD and
      osteoporosis, and possibly to delay or prevent cognitive loss or Alzheimer's
      disease (AD). To test the validity of favorable findings in many small-scale
      studies, and in clinical practice, a large-scale trial: the Women's Health
      Initiative (WHI) was undertaken by the National Institutes of Health (NIH), a
      trial that was prematurely ended because of increased CVD complications, despite
      some lessening of hip fractures. This paper suggests that the customary high
      intake of calcium (Ca)-advised to protect against osteoporosis, and the marginal
      magnesium (Mg) intake in the USA, might well be contributory to the adverse CV
      effects, that were all thromboembolic in nature. The procoagulant effect of
      estrogen is intensified by Ca; Mg-which counteracts many steps in the coagulation
      cascade and inhibits platelet aggregation and adhesion-is commonly consumed in
      sub-optimal amounts. The high American dietary Ca/Mg ratio might also be
      contributory to the WHI failure to confirm ERT's favorable mental effects.
      Discussed are mechanisms by which Mg enhances estrogen's central nervous system
      protective effects. Mg's improvement of cerebral blood flow, which improves brain
      metabolism, can also enhance removal of the beta amyloid peptide, accumulation of
      which is implicated in AD.

PMID- 15466950
TI  - Optimal administration dosage of magnesium sulfate for torsades de pointes in
      children with long QT syndrome.
AB  - BACKGROUND: Intravenous administration of magnesium sulphate (MgSO(4)) is a very
      effective and safe treatment for torsades de pointes (TdP) associated with
      acquired long QT syndrome (LQTS) in adults. Discussed here is the efficacy of
      MgSO(4) for TdP in children with congenital and acquired LQTS. METHODS: The
      optimal MgSO(4) dosage and serum magnesium (SMg) was determined in six
      consecutive children with TdP; four had congenital LQTS and two had acquired
      LQTS. A bolus injection of MgSO(4) was given intravenously over 1 to 2 minutes
      followed by continuous infusion for the next 2 to 7 days. RESULTS: Of the six
      patients, five responded completely to the initial bolus of 6.1 +/- 4.2 mg/kg
      (range, 2.3-12 mg/kg). One (a neonate with congenital LQTS) required a total of
      30 mg/kg until complete TdP elimination. Continuous infusion was given at rates
      of 0.3 to 1.0 mg/kg/hr with no recurrence of TdP. SMg concentration was 3.9 +/-
      1.0 mg/dL (2.9-5.4 mg/dL) immediately after bolus injection. CONCLUSION:
      Intravenous MgSO(4) infusion effectively treated TdP in children with LQTS.
      Optimal bolus dosage, infusion rates and SMg concentration were 3 to 12 mg/kg,
      0.5 to 1.0 mg/kg/hr and 3 to 5 mg/dL, respectively.

PMID- 15466951
TI  - Comparison of mechanism and functional effects of magnesium and statin
      pharmaceuticals.
AB  - Since Mg(2+)-ATP is the controlling factor for the rate-limiting enzyme in the
      cholesterol biosynthesis sequence that is targeted by the statin pharmaceutical
      drugs, comparison of the effects of Mg(2+) on lipoproteins with those of the
      statin drugs is warranted. Formation of cholesterol in blood, as well as of
      cholesterol required in hormone synthesis, and membrane maintenance, is achieved
      in a series of enzymatic reactions that convert HMG-CoA to cholesterol. The rate
      limiting reaction of this pathway is the enzymatic conversion of HMG CoA to
      mevalonate via HMG CoA. The statins and Mg inhibit that enzyme. Large trials have
      consistently shown that statins, taken by subjects with high LDL-cholesterol (LDL
      C) values, lower its blood levels 35 to 65%. They also reduce the incidence of
      heart attacks, angina and other nonfatal cardiac events, as well as cardiac,
      stroke, and total mortality. These effects of statins derive less from their
      lowering of LDL-C than from their reduction of mevalonate formation which
      improves endothelial function, inhibits proliferation and migration of vascular
      smooth muscle cells and macrophages, promotes plaque stabilization and
      regression, and reduces inflammation, Mg has effects that parallel those of
      statins. For example, the enzyme that deactivates HMG-CoA Reductase requires Mg,
      making Mg a Reductase controller rather than inhibitor. Mg is also necessary for
      the activity of lecithin cholesterol acyl transferase (LCAT), which lowers LDL-C
      and triglyceride levels and raises HDL-C levels. Desaturase is another Mg
      dependent enzyme involved in lipid metabolism which statins do not directly
      affect. Desaturase catalyzes the first step in conversion of essential fatty
      acids (omega-3 linoleic acid and omega-6 linolenic acid) into prostaglandins,
      important in cardiovascular and overall health. Mg at optimal cellular
      concentration is well accepted as a natural calcium channel blocker. More recent
      work shows that Mg also acts as a statin.

PMID- 15466952
TI  - Clinical efficacy of magnesium supplementation in patients with type 2 diabetes.
AB  - Effects of magnesium (Mg) supplementation on nine mild type 2 diabetic patients
      with stable glycemic control were investigated. Water from a salt lake with a
      high natural Mg content (7.1%) (MAG21) was used for supplementation after
      dilution with distilled water to 100mg/100mL; 300mL/day was given for 30 days.
      Fasting serum immunoreactive insulin level decreased significantly, as did HOMA
      squareR (both p < 0.05). There was also a marked decrease of the mean
      triglyceride level after supplementation. The patients with hypertension showed
      significant reduction of systolic (p < 0.01), diastolic (p = 0.0038), and mean (p
      < 0.01) blood pressure. The salt lake water supplement, MAG21, exerted clinical
      benefit as a Mg supplement in patients with mild type 2 diabetes mellitus.

PMID- 15466953
TI  - Magnesium, insulin resistance and body composition in healthy postmenopausal
      women.
AB  - OBJECTIVE: This study was conducted to determine the association between
      magnesium (Mg), body composition and insulin resistance in 136 sedentary
      postmenopausal women, 50 to 77 years of age. METHODS: Diabetics, hypertensives
      and women on hormonal replacement therapy were excluded and the remaining 74 were
      divided according to BMI> or =25 (obese: OG) and BMI<25 kg/m(2) (non-obese: NOG).
      Nutritional data disclosed that intakes were high for protein and saturated fat,
      low for carbohydrates, polyunsaturated fat and Mg and normal for the other
      nutrients, according to recommended dietary allowances (RDA). Mg values in red
      blood cells (RBC-Mg) and plasma (P-Mg), were determined, as were fasting glucose,
      and insulin levels, Homeostasis Model Assessment (HOMA), body mass index (BMI),
      body fat percent (BF %), abdominal fat (AF) and free fat mass (FFM). RESULTS: RBC
      Mg values were low in both groups when compared with normal values. There were
      significant differences in body composition parameters, HOMA and insulin levels,
      with higher basal insulin levels in OG. RBC-Mg was directly correlated with
      insulin, HOMA and FFM in both groups, according to Pearson correlations. HOMA in
      OG was also directly correlated with BMI, FFM and AF. In NOG, HOMA was only
      correlated with FFM. The low RBC-Mg levels observed were probably due to low Mg
      intake and to deregulation of factors that control Mg homeostasis during
      menopause. CONCLUSIONS: Both Mg deficit and obesity may independently lead to a
      higher risk for insulin resistance and cardiovascular disease.

PMID- 15466955
TI  - In vitro application of endotoxin to thoracic aortas from magnesium-deficient
      rats enhances vascular hyporeactivity to phenylephrine.
AB  - OBJECTIVE: Endotoxin-induced vascular hyporeactivity to phenylephrine (PE) is
      well described in rat aortas, but has not been investigated in those from
      magnesium (Mg)-deficient rats in vitro. METHODS: Segments of thoracic aorta from
      control and Mg-deficient rats were incubated in culture medium for 6 hours in the
      presence or absence of bacterial lipopolysaccharide (LPS; 0.001-10 microg/mL).
      Contractions to PE were measured with or without an inducible nitric oxide
      synthase (iNOS) inhibitor (1400W; 0.1 and 1 microM), a guanylate cyclase
      inhibitor (ODQ; 0.1 and 1 microM), or a potassium channel inhibitor (TEA; 1 and
      10 mM). RESULTS: LPS induced hyporeactivity in a concentration-dependent manner
      under relatively low concentrations (0.001-0.1 microg/mL), however, there was no
      significant difference at 0.1, 1 and 10 microg/mL. LPS-induced hyporeactivity was
      not significantly affected by endothelium-denudation. The hyporeactivity was
      enhanced in thoracic aortas from Mg-deficient rats by LPS (0.01, 0.1 and 1
      microg/mL). LPS (1 microg/mL) induced hyporeactivity was reversed with 1400W, ODQ
      or TEA in both aortas in a concentration-dependent manner, however the degree of
      reversal was weaker in the Mg-deficient rat aorta than in the control rat one.
      iNOS mRNA level was increased by LPS (0.1 microg/mL) and the increment was
      significantly high in Mg-deficient rat thoracic aorta. CONCLUSIONS: From these
      results it is clearly demonstrated that LPS-induced vascular hyporeactivity to PE
      is enhanced in thoracic aorta from Mg-deficient rats, and it is suggested that
      LPS-induced NO production might contribute to the enhancement via stimulation of
      NO-cyclic GMP-potassium channel pathway.

PMID- 15466954
TI  - Effects of magnesium on cardiac excitation-contraction coupling.
AB  - OBJECTIVE: Magnesium regulates a large number of cellular processes. Small
      changes in intracellular free Mg(2+) ([Mg(2+)](i)) may have important effects on
      cardiac excitability and contractility. We investigated the effects of
      [Mg(2+)](i) on cardiac excitation-contraction coupling. METHODS: We used our
      ionic-metabolic model that incorporates equations for Ca(2+) and Mg(2+) buffering
      and transport by ATP and ADP and equations for MgATP regulation of ion
      transporters (Na(+)-K(+) pump, sarcolemmal and sarcoplasmic Ca(2+) pumps).
      RESULTS: Model results indicate that variations in cytosolic Mg(2+) level might
      sensitively affect diastolic and systolic Ca(2+), sarcoplasmic Ca(2+) content,
      Ca(2+) influx through L-type channels, efficiency of the Na(+)/Ca(2+) exchanger
      and action potential shape. The analysis suggests that the most important reason
      for the observed effects is a modified normal function of sarcoplasmic Ca(2+)
      ATPase pump by altered diastolic MgATP levels. CONCLUSION: The model is able to
      reproduce qualitatively a sequence of events that correspond well with
      experimental observations during cardiac excitation-contraction coupling in
      mammalian ventricular myocytes.

PMID- 15466956
TI  - Geographical variations in heart deaths and diabetes: effect of climate and a
      possible relationship to magnesium.
AB  - BACKGROUND: Geographical variations in deaths from heart disease and the
      prevalence of diabetes occur in the United States. METHODS: These geographical
      variations, by state, were compared to the tertiles of the Z-score (Z-climate)
      obtained from the mean annual temperature and precipitation, by state, and to the
      tertiles of the Z-score (Z-environment) obtained from six environmental factors,
      by state, in monovariant analyses of variance. RESULTS: Both Z-scores were
      significantly related to male heart deaths (Z-climate: p = 0.000009; Z
      environment: p = 0.000043) with Z-climate being the most significant. Both Z
      scores were significantly related to the 1998 prevalence of diabetes (Z-climate:
      p = 0.00018; Z-environment: p = 0.0059) with the climate again being the most
      significant. CONCLUSIONS: Increased temperature can increase magnesium sweat
      losses, which may not be compensated by diet or water intake. Climate
      relationships to these diseases need further investigation.

PMID- 15466957
TI  - The case for a subcutaneous magnesium product and delivery device for space
      missions.
AB  - Cardiovascular (CV) complications, associated with space flight (SF), are caused
      by microgravity, hypokinesia and radiation, particularly beyond earth orbit, with
      all three conducive to oxidative stress. Except for emergencies, pharmaceuticals
      appear to be contraindicated, because of unpredictable side effects from
      malabsorption (M) and potential hepatic and renal impairment. Magnesium (Mg)
      depletion and elevations of cytokines (interleukin 6) occur during SF, conducive
      to self-sustaining vascular inflammation mechanisms. There are potential
      endothelial injuries (EI) and reduced Cyclic GMP (a second messenger of nitric
      oxide: NO) and elevated urinary excretion of C-peptide (insulin resistance: IR).
      Recent findings that show reductions in vascular endothelial growth factor (VEGF)
      suggest that this may result from SF-related thrombocytopenia since platelets (P)
      are the major source of VEGF, and that NO might play a role. Both VEGF and Mg are
      vital for angiogenesis, endothelial function and reendothelialization. Insulin is
      necessary for VEGF expression. To prevent SF-related CV complications in the
      presence of IR and M and with the potential for renal insufficiency, closely
      monitored subcutaneous (SC) Mg should be provided. The dosage can be monitored by
      sublingual intracellular Mg assays. Needed is development of a SC Mg reservoir
      device, which can be replenished before extra-vehicular activities (EVA) and
      which must be reliable despite vigorous movements during EVA, that can last up to
      8 hours. This could also be protective against decompression sickness and EVA
      related 100% oxygen requirements before and during this activity, both of which
      predispost to EI.

PMID- 15466958
TI  - Magnesium attenuates post-traumatic depression/anxiety following diffuse
      traumatic brain injury in rats.
AB  - OBJECTIVE: Magnesium (Mg) declines after traumatic brain injury (TBI), a decline
      believed associated with ensuing neuronal cell death and subsequent functional
      impairment. While Mg's effects on motor and cognitive deficits following TBI have
      been well studied, few studies have addressed post-traumatic depression as an
      outcome parameter, despite its being a major clinical problem with an incidence
      of between 6 and 77%. We investigated the incidence of post-traumatic
      depression/anxiety in an animal model of diffuse TBI, and explored the use of
      magnesium sulfate (MgSO(4)) as an interventional treatment. METHODS: Diffuse TBI
      was induced in 32 anesthetized, adult, male Sprague-Dawley rats, using the 2 m
      impact-acceleration model of injury. At 30 min after injury, half of the rats
      received 250 micromol/kg i.v. MgSO(4); the other half served as non-treated
      controls. Before and for 6 weeks after injury, the open-field, spontaneous
      activity test was used to determine post-traumatic depression/anxiety relative to
      pre-injury. In this test, animals are placed in a 1-meter square box with 100
      squares marked on the base. The number of squares entered in a 5-min period is
      recorded. Incidence of post-traumatic depression/anxiety was defined as the
      number of animals demonstrating a reduction in spontaneous activity to less than
      100 squares in 5 min. Prior to injury, rats typically entered a mean of 201 +/-
      12 (SEM) squares over a 5 min observation period. RESULTS: At 1 week after
      injury, non-treated animals had a mean core of 62 +/- 13. The incidence of post
      traumatic depression/anxiety in these animals was 61%, which is similar to that
      observed clinically. In contrast, animals treated with MgSO(4) had a mean
      activity score of 144 +/- 23 at 1 week after TBI and an incidence of
      depression/anxiety of less than 30%. The significant difference between groups
      persisted for the entire 6-week observation period. CONCLUSIONS: The improvement
      in post-traumatic depression/anxiety conferred by Mg adds further weight to
      available evidence of Mg's benefit as a neuroprotective agent after TBI.

PMID- 15466959
TI  - Amiloride increases neuronal damage after traumatic brain injury in rats.
AB  - OBJECTIVE: It is well known that traumatic brain injury (TBI) decreases brain
      free magnesium (Mg) concentration, and that administration of Mg salts after TBI
      restores concentration of Mg in brain and improves functional outcome. In the
      presence of hemorrhage, administration of Mg salts exacerbates the injury process
      and worsens outcome. An alternative to administration of Mg salts may be to
      prevent cellular loss of Mg with use of amiloride, which inhibits the
      Na(+)/Mg(2+) exchange. METHODS: In the present study, male, adult Sprague-Dawley
      rats were injured using the impact acceleration model of diffuse TBI and
      administered either 100 mols/kg i.v. amiloride, or an equal volume of 50%
      DMSO/saline, 30 minutes (min) after injury. RESULTS: Amiloride did not improve
      functional outcome (motor or cognitive outcome) after TBI relative to vehicle
      treated controls. Histologically, treatment with amiloride significantly
      increased hippocampal caspase-3 expression (apoptosis), axonal swellings in the
      medulla and the degree of dark cell change (cell stress) in the cortex.
      Phosphorus NMR demonstrated that amiloride did not increase free Mg concentration
      after injury. CONCLUSIONS: Thus, amiloride is ineffective in preventing Mg loss
      after TBI when administered 30 min after trauma. Moreover, by administering
      amiloride after the TBI-related Mg decline has already been initiated, it may
      exacerbate injury by, in part by inhibiting Na(+)/Mg(2+) antiport and preventing
      entry of Mg back into the cell, and also by inhibiting other Na(+) linked
      transporters.

PMID- 15466960
TI  - A substance P antagonist increases brain intracellular free magnesium
      concentration after diffuse traumatic brain injury in rats.
AB  - OBJECTIVE: Magnesium (Mg) deficiency has been shown to increase substance P
      release and induce a pro-inflammatory response that can be attenuated with the
      administration of a substance P-antagonist. Neurogenic inflammation has also been
      implicated in traumatic brain injury (TBI), a condition where brain intracellular
      free magnesium (Mg(f)) decline is known to occur and has been correlated with
      functional outcome. We therefore examined whether a substance P antagonist
      restores brain intracellular free magnesium concentration following TBI. METHODS:
      Male, adult Sprague-Dawley rats were injured using the Cernak impact acceleration
      model of diffuse TBI. At 30 min after injury, animals were administered either
      0.25 mg/kg i.v. n-acetyl tryptophan or equal volume saline. Prior to and 4 h
      after induction of injury, phosphorus magnetic resonance spectra were acquired
      using a 7-tesla magnet interfaced with a Bruker console. Mg(f) was calculated
      from the chemical shift of the beta ATP. Before injury, Mg(f) was 0.51 +/- 0.05
      mM (SEM). RESULTS: By 4 hr after injury, Mg(f) had significantly declined to 0.27
      +/- 0.02 mM in saline treated rats. In contrast, rats treated with n-acetyl
      tryptophan had a Mg(f) of 0.47 +/- 0.06 mM at 4 h after injury, which was not
      significantly different from preinjury values. There were no significant
      differences in pH between the treatment groups. CONCLUSION: It seems that any
      beneficial effect of a substance P antagonist on functional outcome following TBI
      may be related to improvement in brain Mg homeostasis induced by the compound.

PMID- 15466961
TI  - Magnesium gluconate offers no more protection than magnesium sulphate following
      diffuse traumatic brain injury in rats.
AB  - OBJECTIVE: Previous studies have demonstrated that magnesium salts, including the
      sulphate and chloride forms, are neuroprotective following traumatic brain injury
      (TBI). Recently, studies in cardiac ischaemia/reperfusion injury have
      demonstrated that the gluconate salt of magnesium may provide superior protection
      against oxidative damage and postischaemic dysfunction than MgSO(4). We have
      therefore compared the efficacy of both MgSO(4) and magnesium gluconate (MgGl(2))
      on outcome following diffuse TBI in rats. METHODS: Adult male Sprague-Dawley rats
      were injured using the 2-metre impact acceleration model of diffuse TBI. At 30
      min after injury, animals were administered with either 250 micromoles/kg i.v.
      MgSO(4), MgGl(2), or equal volume saline vehicle. Thereafter, animals were
      assessed for motor and cognitive outcome using the rotarod and Barnes maze,
      respectively, or their brains removed at 3 days after TBI and used for
      histological examination. RESULTS: Treatment with either magnesium salt
      significantly improved functional outcome as compared to vehicle treated
      controls. Similarly, treatment with either magnesium salt attenuated the degree
      of histological dark cell change at 3 days after TBI relative to the vehicle
      treated animals. There were no significant differences between the magnesium
      treated groups. CONCLUSIONS: We conclude that MgSO(4) and MgGl(2) are equally
      neuroprotective following TBI. Our results suggest that MgGl(2) may only be more
      effective in conditions that produce ischaemia, where high concentrations of
      reactive oxygen species are generated.

PMID- 15466962
TI  - Magnesium VitB6 intake reduces central nervous system hyperexcitability in
      children.
AB  - OBJECTIVE: Ionic magnesium (Mg(2+)) depletion has long been known to cause
      hyperexcitability with convulsive seizures in rodents, effects that have been
      reversed by treatment with magnesium (Mg). Metabolic disorders and genetic
      alterations are suspected in this pathology, in which Mg(2+) transport and
      intracellular distribution may be reduced without change in serum Mg(2+)
      concentrations. We evaluated the effects of Mg(2+)/vitamin B6 regimen on the
      behavior of 52 hyperexcitable children (under 15 years of age) and their
      families. METHODS: To assess intracellular Mg(2+), we measured intra-erthrocyte
      Mg(2+) levels (ERC-Mg). Our reference values for normal subjects were 2.46 to
      2.72 mmol/L. In 30 of the 52 hyperactive children, there were low ERC-Mg values:
      2.041 +/- 0.279 mmol/L). Combined Mg(2+)/vitamin B6 intake (100 mg/day) for 3 to
      24 weeks restored normal ERC-Mg values (2.329 +/- 0.386 mmol/L). RESULTS: In all
      patients, symptoms of hyperexcitability (physical aggressivity, instability,
      scholar attention, hypertony, spasm, myoclony) were reduced after 1 to 6 months
      treatment. Other family members shared similar symptoms, had low ERC-Mg values,
      and also responded clinically to increased Mg(2+)/vitamin B6 intakes. Two typical
      families are described. CONCLUSION: This open study indicates that hyperexcitable
      children have low ERC-Mg with normal serum Mg(2+) values, and that Mg(2+)/vitamin
      B6 supplementation can restore normal ERC-Mg levels and improve their abnormal
      behavior.

PMID- 15466963
TI  - The influence of some antipsychotics on erythrocyte magnesium and plasma
      magnesium, calcium, copper and zinc in patients with paranoid schizophrenia.
AB  - OBJECTIVE: The aim of the study was the investigation of plasma magnesium,
      calcium, copper and zinc and erythrocyte magnesium levels in patients with
      paranoid schizophrenia and the influence of the therapy with two antipsychotic
      drugs (haloperidol and risperidone) on these concentrations. METHODS: We
      investigated the influence of treatment with haloperidol and risperidoneon plasma
      and erythrocyte magnesium and on plasmatic levels of zinc, calcium and copper on
      hospitalized 56 patients diagnosed with paranoid schizophrenia (DSM IV). RESULTS:
      Our data indicate a decrease of erythrocyte magnesium levels in schizophrenic
      patients (4.82 +/- 3.1 mg/L vs. 59.2 +/- 1.1 mg/L in control group, p < 0.01).
      The plasma level of magnesium was unchanged (18.9 +/- 2.17 mg/L in schizophrenic
      patients vs. 18.26 +/- 1.9 mg/L in control group). CONCLUSIONS: We consider
      plasma Cu(2+)/erythrocyte Mg(2+) and plasma Cu(2+)/Zn(2+) ratio two important
      biological markers of the acute paranoid schizophrenia.

PMID- 15466964
TI  - The determination of brain magnesium and zinc levels by a dual-probe
      microdialysis and graphite furnace atomic absorption spectrometry.
AB  - OBJECTIVE: The aim of this study was to develop a microdialysis-graphite furnace
      atomic absorption spectroscopy (MD-GFAAS) for monitoring dynamic changes of
      extracellular magnesium (Mg) and zinc (Zn) in the cortex of gerbils subjected to
      focal cerebral ischemia, that had been produced in anesthetized gerbils by
      occlusion of the right middle cerebral artery. METHODS: Two microdialysis probes
      were inserted into both sides of the cortex to simultaneously collect dialysates
      during cerebral ischemia. Dynamic changes in these analytes, on ipsilateral and
      contralateral sides of the brain, were assayed by MD-GFAAS. Optimal conditions
      and analytical precision of GFAAS were studied in the present assay. RESULTS: The
      present study demonstrated significant decreases in Mg (65% of baseline) and zinc
      (74% of baseline) maintained their levels within 3 h on the ipsilateral side of
      cortex during cerebral ischemia. Slight changes of Mg and Zn on the contralateral
      sides were also observed. CONCLUSION: The derangement of extracellular Mg and Zn
      could be important in the progression of cell injury and may be associated with
      cerebral ischemia insult.

PMID- 15466965
TI  - Microdialysis analyzer and flame atomic absorption spectrometry in the
      determination of blood glucose, lactate and magnesium in gerbils subjected to
      cerebral ischemia/reperfusion.
AB  - OBJECTIVE: Flame atomic absorption spectrometry (FAAS) and a microdialysis
      analyzer were employed for dynamic monitoring of magnesium (Mg), glucose and
      lactate levels in blood samples of gerbils subjected to cerebral ischemia.
      METHODS: Focal cerebral ischemia was induced by occlusion of the unilateral
      common carotid artery and the middle cerebral artery for 60 minutes followed by
      180 minutes of reperfusion. Whole blood samples were continuously collected from
      the jugular vein via an auto-blood sampling system. The dynamic profiles of Mg,
      glucose and lactate before, during and after ischemia were determined. RESULTS:
      During cerebral ischemia, blood Mg levels gradually rose to 130% of the baseline
      and returned to the basal levels within 30 minutes after reperfusion. Lactate
      concentrations decreased to approximately 50% of the basal levels during cerebral
      ischemia and returned to basal levels immediately after reperfusion. Glucose
      levels remained the same during cerebral ischemia and gradually fell to 50% of
      basal levels at the end of reperfusion. The linearity ranges of glucose, lactate
      and Mg were 0.1-25 mM, 0.02-2.5 mM and 5-1500 microg/L, respectively. The
      required volume of each blood sample is less than 30 microL. The intra- and inter
      assay variation was less than 3%. Since blood loss is minimal from repeated blood
      sampling, it is suitable for small animals. CONCLUSIONS: Mg may be accumulated in
      blood cells, which are helpful for reducing glucose utilization. As a result,
      less lactate was produced during the acute phase of cerebral ischemia.
      Preservation of glucose is advantageous for brain cells' restoration after
      ischemia.

PMID- 15466966
TI  - On-line microdialysis-graphite furnace atomic absorption spectrometry in the
      determination of brain magnesium levels in gerbils subjected to cerebral
      ischemia/reperfusion.
AB  - OBJECTIVES: Description of use of equipment for on-line microdialysis (MD)
      coupled with graphite furnace atomic absorption spectrometry (GFAAS) system, for
      dynamic monitoring of extracellular Mg in gerbils subjected to transient focal
      cerebral ischemia. METHODS: Gerbils' right middle cerebral artery (MCA) and
      common carotid artery (CCA) were occluded for 60 minutes, and then reperfused for
      60 minutes with Ringer's solution, after which extracellular fluid samples were
      collected via a microdialysis probe inserted into the right cortex before, during
      and after inducing ischemia. Reperfusion was at a rate of 2 microL/min through
      the microdialysis probe, on-line diluted with measured water injected onto the
      GFAAS via an autosampler for Mg analysis. RESULTS: The detection limit of the Mg
      concentrations has ranged from 0.50 to 3.00 microg/L; our detection limit was
      0.03 microg/L. We applied this on-line system to monitor extracellular Mg levels
      in the cortex during focal cerebral ischemia. Mg concentrations significantly
      decreased to 41% of baseline during cerebral ischemia and gradually returned to
      67% of baseline after 60 minutes of reperfusion. CONCLUSIONS: We presume that
      derangement of Mg homeostasis could be important in brain cell injury and is
      closely associated with cerebral ischemia event. The described analytic system
      permits autosampling in the brain and allows for continuous determination of Mg
      and trace minerals in minute sample volumes in a living system.

PMID- 15466968
TI  - Pediatric cancer in the United States: the Children's Oncology Group Epidemiology
      Research Program.

PMID- 15466969
TI  - Defining the role of mass spectrometry in cancer diagnostics.

PMID- 15466970
TI  - Etiology of hormone receptor-defined breast cancer: a systematic review of the
      literature.
AB  - Breast cancers classified by estrogen receptor (ER) and/or progesterone receptor
      (PR) expression have different clinical, pathologic, and molecular features. We
      examined existing evidence from the epidemiologic literature as to whether breast
      cancers stratified by hormone receptor status are also etiologically distinct
      diseases. Despite limited statistical power and nonstandardized receptor assays,
      in aggregate, the critically evaluated studies (n = 31) suggest that the etiology
      of hormone receptor-defined breast cancers may be heterogeneous. Reproduction
      related exposures tended to be associated with increased risk of ER-positive but
      not ER-negative tumors. Nulliparity and delayed childbearing were more
      consistently associated with increased cancer risk for ER-positive than ER
      negative tumors, and early menarche was more consistently associated with ER
      positive/PR-positive than ER-negative/PR-negative tumors. Postmenopausal obesity
      was also more consistently associated with increased risk of hormone receptor
      positive than hormone receptor-negative tumors, possibly reflecting increased
      estrogen synthesis in adipose stores and greater bioavailability. Published data
      are insufficient to suggest that exogenous estrogen use (oral contraceptives or
      hormone replacement therapy) increase risk of hormone-sensitive tumors. Risks
      associated with breast-feeding, alcohol consumption, cigarette smoking, family
      history of breast cancer, or premenopausal obesity did not differ by receptor
      status. Large population-based studies of determinants of hormone receptor
      defined breast cancers defined using state-of-the-art quantitative immunostaining
      methods are needed to clarify the role of ER/PR expression in breast cancer
      etiology.

PMID- 15466971
TI  - Incidence of invasive breast cancer and ductal carcinoma in situ in a screening
      program by age: should older women continue screening?
AB  - OBJECTIVE: The evidence for the effectiveness of screening is strongest for women
      ages 50 to 69 years; however, there is variation in the target age group for
      screening programs between different countries. In particular, there is
      uncertainty over whether women should continue screening once they reach age 70.
      We therefore investigated incidence rates for invasive and in situ breast cancer
      by age as well as prognostic features of tumors within a screening program.
      METHODS: We studied 474,808 women who attended BreastScreen Victoria from January
      1, 1993 to December 31, 2000. Of these women, 5,301 were diagnosed with invasive
      cancer and 1,127 were diagnosed with ductal carcinoma in situ. We used
      generalized additive models to model age-incidence rates for invasive cancers and
      ductal carcinoma in situ separately by users and nonusers of hormone replacement
      therapy at most recent screen. Nonparametric trends for ordered groups and
      regression methods were used to investigate trends in size, grade, and nodal
      involvement for invasive tumors by type of attendance and time since previous
      negative screen for age group. RESULTS: The incidence of ductal carcinoma in situ
      among women with a previous negative screen clearly declined after age 70
      irrespective of hormone replacement therapy use. At subsequent screen, the age
      incidence curve for invasive breast cancer flattened at ages 60 to 75 years and
      then increased only for women taking hormone replacement therapy. Tumor size at
      diagnosis declined with age at both first round (P = 0.15) and subsequent round
      (P = 0.08). The proportion of poorly differentiated tumors also decreased with
      age, with the smallest proportion of grade III tumors diagnosed in women ages >
      or = 75 years (P = 0.09 for first screen and P = 0.05 for subsequent screen). The
      presence of positive nodes at diagnosis declined with age (P < 0.001) for both
      first and subsequent screening rounds. CONCLUSION: Older age is associated with
      more favorable prognostic tumor features and a lower incidence of ductal
      carcinoma in situ among subsequent attenders of screening. When making decisions
      regarding continuing screening, older women and their physicians should also
      consider the presence of other comorbid conditions that may mitigate any impact
      of screening on mortality.

PMID- 15466972
TI  - A case-control study of risk factors for invasive cervical cancer among U.S.
      women exposed to oncogenic types of human papillomavirus.
AB  - Oncogenic human papillomavirus (HPV) infections, the necessary cause of most
      cervical cancers, are common and usually clear within 1 to 2 years. Identifying
      cofactors that lead to cancer among HPV-infected women has depended mainly on
      case-control studies defining HPV by DNA testing. DNA testing assesses only
      current infection; thus, concerns about residual confounding remain. To assess
      cofactors, we used seropositivity to five oncogenic HPV types as a marker of past
      exposure and confined our analysis to seropositive controls compared with cancer
      cases. Study subjects had participated in a multicenter U.S. case-control study
      conducted in the early 1980s. The detailed questionnaire and stored sera for 235
      cases of squamous carcinoma and 486 controls motivated the reanalysis. We
      measured antibodies to HPV types 16, 18, 31, 45, and 52. Independent, significant
      predictors of seropositivity among controls included numbers of sexual partners,
      Black race, and oral contraceptive use. Condom use was protective. Among HPV
      exposed women, Papanicolaou screening, Black race, and yeast infection were
      significantly associated with reduced cancer risk. Current smoking was associated
      with a 2-fold increase in risk; there were independent, significant trends of
      increased risk with numbers of cigarettes smoked (P for trend = 0.003) and years
      of smoking (P for trend = 0.01). Other significant predictors of increased risk
      included low education and income and history of nonspecific genital infection.
      Unlike recent HPV DNA-based investigations, based on the use of HPV-seropositive
      controls in this study, oral contraceptive use was unrelated to the risk of
      cervical cancer and multiparity was only weakly related to risk. It is
      particularly worth considering further why studies of different designs are
      inconsistent regarding the effect of oral contraceptive use.

PMID- 15466973
TI  - Reproductive factors and risk of glioma in women.
AB  - OBJECTIVE: Glioma is the most common primary malignant brain tumor in adults,
      responsible for 75% of adult primary malignant brain tumors, yet aside from its
      association with ionizing radiation, its etiology is poorly understood. Sex
      differences in brain tumor incidence suggest that hormonal factors may play a
      role in the etiology of these tumors, but few studies have examined this
      association in detail. The objective of this study was to explore the role of
      reproductive factors in the etiology of glioma in women. METHOD: As part of a
      population-based case-control study, histologically confirmed primary glioma
      cases (n = 341 women) diagnosed between January 1, 1995 and January 31, 1997 were
      identified through clinics and hospitals in four Midwest U.S. states. Controls (n
      = 527 women) were randomly selected from lists of licensed drivers and Health
      Care Finance Administration enrollees. In-person interviews with subjects (81%)
      or their proxies (19%) collected reproductive history and other exposure
      information. RESULTS: Glioma risk increased with older age at menarche (P for
      trend = 0.009) but only among postmenopausal women. Compared with women who never
      breast-fed, women who breast-fed >18 months over their lifetime were at increased
      risk of glioma (odds ratio, 1.8; 95% confidence interval, 1.1-2.9). Women who
      reported using hormones for symptoms of menopause had a decreased risk of glioma
      compared with women who never used such hormones (odds ratio, 0.7; 95% confidence
      interval, 0.5-1.1). CONCLUSION: These results support the hypothesis that
      reproductive hormones play a role in the etiology of glioma among women.

PMID- 15466974
TI  - STK15 polymorphisms and association with risk of invasive ovarian cancer.
AB  - STK15 is a putative oncogene that codes for a centrosome-associated,
      serine/threonine kinase, the normal function of which is to ensure accurate
      segregation of chromosomes during mitosis. Amplification of STK15 has been
      reported in ovarian tumors, suggesting a role in ovarian cancer pathology. STK15
      is polymorphic with two single nucleotide substitutions (449t/a and 527g/a) in
      evolutionarily conserved regions causing amino acid changes (F31I and V57I). Two
      other nucleotide substitutions (287c/g and 1891g/c) of unknown significance are
      in 5' and 3' untranslated regions (UTR), respectively. To learn more about the
      involvement of STK15 in ovarian cancer, we genotyped and haplotyped these
      polymorphisms in three population-based ovarian cancer case-control studies from
      the United Kingdom, United States, and Denmark with 1,821 combined cases and
      2,467 combined controls and calculated risks for developing ovarian cancer.
      Genotypes of individual polymorphisms in control groups of the United Kingdom,
      United States, and Denmark conformed to Hardy-Weinberg equilibrium. In combined
      cases and combined controls, rare allele frequencies were 0.23 and 0.21 for I31,
      0.16 and 0.17 for I57, 0.08 and 0.07 for 5' UTR g, and 0.25 and 0.24 for 3' UTR
      c, respectively. Using FF common homozygotes of F31I as comparator, there was
      increased ovarian cancer risk to FI heterozygotes (odds ratio, 1.18; 95%
      confidence interval, 1.01-1.36), II homozygotes (odds ratio, 1.25; 95% confidence
      interval, 0.89-1.75), and I31 allele carriers (odds ratio, 1.17; 95% confidence
      interval, 1.02-1.35) in the combined group data. For either V57I, 5' UTR C/G, or
      3' UTR G/C, all genotypic ovarian cancer risks were essentially in unity relative
      to their respective common homozygotes, VV, cc, or gg. Haplotype analysis of
      combined group data revealed seven haplotypes with frequencies between 0.02 and
      0.5, with c-F-V-g the most common. None of the haplotype-specific risks
      significantly differed from unity relative to c-F-V-g. These results suggest a
      model of dominant inheritance of ovarian cancer risk by the I31 allele of F31I
      and that the I31 allele may be a common ovarian cancer susceptibility allele of
      low penetrance.

PMID- 15466975
TI  - Association of nut and seed intake with colorectal cancer risk in the European
      Prospective Investigation into Cancer and Nutrition.
AB  - A link between unsaturated fatty acids or phytonutrients and reduced risk of
      colorectal cancer has been suggested. However, the effects of higher intake of
      dietary sources of these nutrients, such as the nuts and seeds food group, are
      less clear. The objective of this study was to determine the effects of nut and
      seed intake on colorectal cancer risk within the European Prospective
      Investigation into Cancer and Nutrition study, a large prospective cohort study
      involving 10 European countries. Total nut and seed intake was determined from
      country-specific dietary questionnaires. The data set included 478,040 subjects
      (141,988 men, 336,052 women) with a total of 855 (327 men, 528 women) colon and
      474 (215 men, 259 women) rectal cancer cases. A multivariate Cox proportional
      hazards model, stratified by center and controlled for fruit intake, dietary
      fiber, energy, height, weight, sex, age, physical activity, and smoking, was
      used. The data show no association between higher intake of nuts and seeds and
      risk of colorectal, colon, and rectal cancers in men and women combined, but a
      significant inverse association was observed in subgroup analyses for colon
      cancer in women at the highest (>6.2 g/d) versus the lowest (nonconsumers; hazard
      ratio, 0.69; 95% confidence interval, 0.50-0.95) category of intake and for the
      linear effect of log-transformed intake (hazard ratio, 0.89; 95% confidence
      interval, 0.80-0.98), with no associations in men. It is not evident from this
      data why there may be a stronger association in women or why it may be limited to
      the colon, suggesting that much further research is necessary.

PMID- 15466976
TI  - Overexpression of m-calpain in human colorectal adenocarcinomas.
AB  - BACKGROUND: Calpains represent a well-conserved family of Ca2+ -dependent
      proteolytic enzymes. Recently, the importance of calpain in the metastatic
      process has received great attention. To investigate whether m-calpain
      contributes to the pathogenesis of colorectal cancer, we investigated the
      expression of m-calpain and its inhibitors, calpastatin and high-molecular-weight
      calmodulin-binding protein (HMWCaMBP), in human colorectal surgical specimens.
      METHODS: Fifty cases of colon carcinoma were evaluated for this study. Of 50
      cases evaluated, we presented in this report six cases for m-calpain, calpastatin
      and HMWCaMBP protein expression by Western blot analyses was done in both normal
      and invasive tumor components of human samples. In addition, immunohistochemistry
      analysis was also carried out in all patients. RESULTS: The activity and protein
      expression of m-calpain was significantly higher in colorectal adenocarcinoma
      than in normal colonic mucosa. This finding was corroborated by
      immunohistochemical studies that showed strong cytoplasmic staining in the colon
      tumors with m-calpain antibody. The decreased expression of these calpain
      inhibitors (calpastatin and HMWCaMBP) paralleled increased activity and
      expression of calpain in colorectal adenocarcinoma and the well-documented
      involvement of this Ca2+ -dependent protease in colon tumor. CONCLUSION:
      Increased activity and moderate staining of m-calpain in polyps show the usage of
      this enzyme as a marker for the early detection of colorectal adenocarcinoma
      using immunologic approaches. These findings represent the first description of
      calpain overexpression in colorectal cancer. This has implications with regard to
      the design of chemotherapeutic drugs as well as in monitoring colorectal cancer
      in early stages of the metastatic process.

PMID- 15466977
TI  - Dietary amelioration of Helicobacter pylori infection: design criteria for a
      clinical trial.
AB  - The longitudinal stability of the urea breath test (UBT), which measures urease
      as a biomarker for infection with Helicobacter pylori (a major risk factor for
      gastric cancer), was evaluated in the environs of Tsukuba, Japan. 13C-UBT
      measurements were monitored at four time points in 46 free-living, H. pylori
      infected, asymptomatic volunteers over a period of 7 weeks. Subjects were asked
      to refrain from eating cruciferous vegetables, which might confound
      interpretation of results. Their compliance was monitored using both dietary
      records and direct biochemical testing of overnight urine. There was large
      between-subject UBT variation in this population (logUBT mean, 3.34; SD, 0.67).
      Within-subject (longitudinal) UBT values were remarkably stable in about one
      quarter of the subjects (coefficients of variations for these individuals were
      <21%), whereas coefficients of variations in the highest quartile of variability
      ranged from 40% to 80%. About half of the sequential UBTs (63 of 138 such
      measurement pairs) changed >10 per thousand "delta over baseline" between
      measurements. This study provides the elements to optimize the design of a
      clinical trial in this population to examine the efficacy of a dietary
      intervention to reduce H. pylori infection. The number of subjects required to
      detect a 30% difference in average UBT value is highly dependent on the baseline
      stability of UBT measurements. For the least variable quartile, as few as 12
      subjects would be needed; for the most variable quartile, at least 147 subjects
      would be required in each arm.

PMID- 15466978
TI  - A comparison of urinary biomarkers of tobacco and carcinogen exposure in smokers.
AB  - Recently, several potential harm reduction strategies, such as reduction in the
      number of cigarettes smoked and the use of modified cigarette products, have been
      discussed as possible means by which to reduce tobacco-related disease. To assess
      any potential reduction in harm by either of these approaches requires an
      accurate assessment of tobacco toxin exposure. We have recently completed a
      cigarette reduction study in which smokers were required to reduce the number of
      cigarettes smoked by 75%. This reduction took place over a 6-week period. We
      report here the comparison of urinary concentrations of tobacco alkaloid and
      tobacco carcinogen biomarkers in a subset of these same smokers during a 7-week
      period prior to any reduction in cigarette consumption. Urine samples were
      collected at four time points and analyzed for 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanol (NNAL), and its glucuronide, 1-hydroxypyrene, anatabine, free
      nicotine, total nicotine (free plus glucuronidated), free cotinine, total
      cotinine (free plus glucuronidated), and total trans-3'-hydroxycotinine (free
      plus glucuronidated). Anatabine is a minor alkaloid that may be useful in
      assessing tobacco exposure in individuals using nicotine replacement therapies.
      Urinary anatabine levels were well correlated (P < 0.0001) with both free and
      total nicotine (r = 0.753 and 0.773, respectively). Anatabine levels were also
      correlated with free cotinine (r = 0.465; P < 0.001), total cotinine (r = 0.514;
      P < 0.001), and total NNAL (r = 0.633; P < 0.001). These data support the role of
      anatabine as a biomarker of tobacco exposure. 1-Hydroxypyrene is a biomarker of
      polycyclic aromatic hydrocarbon exposure, but unlike NNAL it is not tobacco
      specific. Whereas urinary concentrations of 1-hydroxypyrene were consistent
      across the four visits, the levels were not correlated with NNAL, anatabine,
      nicotine, or any nicotine metabolites.

PMID- 15466979
TI  - Chlamydia pneumoniae infection and risk of lung cancer.
AB  - Infection with Chlamydia pneumoniae may be associated with an increased risk of
      lung cancer. We conducted a matched case-control study (508 pairs) nested within
      a large prospective study to investigate whether IgA antibody titers to C.
      pneumoniae measured by the microimmunofluorescence test are associated with lung
      cancer risk after controlling for confounders. Individuals with antibody titers >
      or = 16 had 1.2 times the risk of lung cancer (95% confidence interval, 0.9-1.6)
      compared to those with lower titers. There was a significant trend (P = 0.007) of
      increasing odds ratios with increasing IgA titers primarily due to an odds ratio
      of 2.8 (95% confidence interval, 1.1-6.7) associated with titers > or = 256. Lung
      cancer risk associated with IgA titers > or = 16 was stronger among former
      smokers. To better understand predictors of IgA seropositivity, we also examined
      demographic, lifestyle, dietary, and medical correlates of IgA titers > or = 16
      among controls. Those with race not classified as White or Black were more likely
      to have IgA titers > or = 16; there were no significant differences in
      seropositivity by smoking behaviors. In summary, the adjusted odds ratio for lung
      cancer associated with IgA titers > or = 16 was compatible with a weakly positive
      association, although nondifferential measurement error of antibody titers may
      have resulted in a conservative bias. Future studies using precise measures of
      chronic C. pneumoniae status are needed to better determine the role of this
      organism in the etiology of lung cancer.

PMID- 15466980
TI  - Effects of genetic polymorphisms of metabolic enzymes on cytokinesis-block
      micronucleus in peripheral blood lymphocyte among coke-oven workers.
AB  - Exploring the associations between genetic polymorphisms of metabolic enzymes and
      susceptibility to polycyclic aromatic hydrocarbon (PAH)-induced chromosomal
      damage is of great significance for understanding PAH carcinogenesis. Cytochrome
      P450, glutathione S-transferase, microsomal epoxide hydrolase, NAD(P)H:quinone
      oxidoreductase, and N-acetyltransferase are PAH-metabolizing enzymes. In this
      study, we genotyped for the polymorphisms of these genes and assessed their
      effects on cytokinesis-block micronucleus (CBMN) frequencies in peripheral blood
      lymphocytes among 141 coke-oven workers and 66 non-coke-oven worker controls. The
      geometric means of urinary 1-hydroxypyrene levels in coke-oven workers and the
      controls were 12.0 and 0.7 micromol/mol creatinine, respectively (P < 0.01). The
      CBMN frequency (number of micronuclei per 1,000 binucleated lymphocytes) was
      significantly higher in coke-oven workers (9.5 +/- 6.6 per thousand) than in the
      controls (4.0 +/- 3.6 per thousand; P < 0.01). Among the coke-oven workers, age
      was positively associated with CBMN frequency; the mEH His113 variant genotype
      exhibited significantly lower CBMN frequency (8.5 +/- 6.5 per thousand) than did
      the Tyr113/Tyr113 genotype (11.3 +/- 6.4 per thousand; P < 0.01); the low mEH
      activity phenotype exhibited a lower CBMN frequency (8.6 +/- 6.8 per thousand)
      than did the high mEH activity phenotype (13.2 +/- 6.7 per thousand; P = 0.01);
      the GSTP1 Val105/Val105 genotype exhibited a higher CBMN frequency (15.0 +/- 5.8
      per thousand) than did the GSTP1 Ile105/Ile105 or Ile105/Val105 genotypes (9.3 +/
      6.5 per thousand; P < 0.01); the joint effect of high mEH activity phenotype and
      GSTM1 null genotype on CBMN frequencies was also found. Gene-environment
      interactions between occupational PAH exposure and polymorphisms of mEH and/or
      GSTM1 were also evident. These results indicate that the mEH, GSTP1, and GSTM1
      polymorphisms may play a role in sensitivity or genetic susceptibility to the
      genotoxic effects of PAH exposure in the coke-oven workers.

PMID- 15466981
TI  - Prostate-specific antigen and free prostate-specific antigen in the early
      detection of prostate cancer: do combination tests improve detection?
AB  - BACKGROUND: The combined use of free and total prostate-specific antigen (PSA) in
      early detection of prostate cancer has been controversial. This article
      systematically evaluates the discriminating capacity of a large number of
      combination tests. METHODS: Free and total PSA were analyzed in stored serum
      samples taken prior to diagnosis in 429 cases and 1,640 controls from the
      Physicians' Health Study. We used a classification algorithm called logic
      regression to search for clinically useful tests combining total and percent free
      PSA and receiver operating characteristic analysis and compared these tests with
      those based on total and complexed PSA. Data were divided into training and test
      subsets. For robustness, we considered 35 test-train splits of the original data
      and computed receiver operating characteristic curves for each test data set.
      RESULTS: The average area under the receiver operating characteristic curve
      across test data sets was 0.74 for total PSA and 0.76 for the combination tests.
      Combination tests with higher sensitivity and specificity than PSA > 4.0 ng/mL
      were identified 29 out of 35 times. All these tests extended the PSA reflex range
      to below 4.0 ng/mL. Receiver operating characteristic curve analysis indicated
      that the overall diagnostic performance as expressed by the area under the curve
      did not differ significantly for the different tests. CONCLUSIONS: Tests
      combining total and percent free PSA show modest overall improvements over total
      PSA. However, utilization of percent free PSA below a PSA threshold of 4 ng/mL
      could translate into a practically important reduction in unnecessary biopsies
      without sacrificing cancers detected.

PMID- 15466982
TI  - Metabolic syndrome and the risk of prostate cancer in Finnish men: a population
      based study.
AB  - OBJECTIVE: Individual components of metabolic syndrome have been linked to an
      increased risk for prostate cancers. We hypothesized that metabolic syndrome
      itself could confer an increased risk for incident prostate cancer. METHODS: The
      participants were a population-based sample of 1,880 men from eastern Finland
      without history of cancer or diabetes mellitus at baseline. RESULTS: The
      metabolic syndrome (WHO criteria) was present in 357 (19%) of subjects. During an
      average follow-up of 13 years, a total of 183 cancers occurred, of which 56 were
      due to prostate cancer. The metabolic syndrome at baseline was related to a 1.9
      fold (95% confidence interval, 1.1-3.5) risk of prostate cancer after adjustment
      for age, alcohol consumption, physical fitness, and energy, fat, fiber, calcium,
      vitamin E, and alpha-linolenic acid intake. The association between metabolic
      syndrome and risk of prostate cancer was stronger among overweight and obese men
      with a body mass index > or = 27 kg/m2 (adjusted relative risk, 3.0; 95%
      confidence interval, 1.2-7.3) than in lighter men (relative risk, 1.8; 95%
      confidence interval, 0.7-4.7). CONCLUSIONS: Middle-aged men with the metabolic
      syndrome were more likely to develop prostate cancer in this prospective
      population-based study. This finding suggests that efforts to curb the epidemic
      of overweight and sedentary lifestyle and the accompanying metabolic syndrome may
      decrease the risk for prostate cancer.

PMID- 15466983
TI  - Cancer-related anorexia/cachexia syndrome and oxidative stress: an innovative
      approach beyond current treatment.
AB  - OBJECTIVE: Cancer-related anorexia/cachexia syndrome and oxidative stress play a
      key role in the progression and outcome of neoplastic disease. PATIENTS AND
      METHODS: On the basis of our previously published studies and clinical
      experience, we have developed an innovative approach consisting of diet with high
      polyphenol content (400 mg), p.o. pharmaconutritional support enriched with n - 3
      fatty acids (eicosapentaenoic acid and docosahexaenoic acid) 2 cans (237 mL each)
      per day, medroxiprogesterone acetate 500 mg/d, antioxidant treatment with alpha
      lipoic acid 300 mg/d plus carbocysteine lysine salt 2.7 g/d plus vitamin E 400
      mg/d plus vitamin A 30,000 IU/d plus vitamin C 500 mg/d, and selective
      cyclooxygenase-2 inhibitor Celecoxib 200 mg/d. The treatment is administered for
      16 weeks. The following variables are evaluated: (a) clinical variables (stage
      and Eastern Cooperative Oncology Group performance status); (b) nutritional
      variables (lean body mass, appetite, and resting energy expenditure); (c)
      laboratory variables (serum levels of proinflammatory cytokines, C-reactive
      protein, and leptin and blood levels of reactive oxygen species and antioxidant
      enzymes); and (d) quality of life variables (European Organization for Research
      and Treatment of Cancer QLQ-C30, EQ-5Dindex, and EQ-5DVAS). A phase II
      nonrandomized study has been designed to enroll 40 patients with advanced cancer
      at different sites with symptoms of cancer-related anorexia/cachexia syndrome and
      oxidative stress. RESULTS: As of January 2004, 28 patients have been enrolled: 25
      patients were evaluable and 14 of them have completed the treatment (20 patients
      have completed 2 months of treatment). As for clinical response, five patients
      improved, three patients remained unchanged, and six patients worsened. The
      Eastern Cooperative Oncology Group performance status (grade) 1 remained
      unchanged. As for nutritional/functional variables, the lean body mass increased
      significantly at 2 and 4 months. As for laboratory variables, reactive oxygen
      species decreased significantly and proinflammatory cytokines interleukin-6 and
      tumor necrosis factor-alpha decreased significantly. As for quality of life, it
      comprehensively improved after treatment. CONCLUSIONS: The treatment has been
      shown to be effective for clinical response, increase of lean body mass, decrease
      of reactive oxygen species and proinflammatory cytokines, and improvement of
      quality of life. The treatment has been shown to be safe with good compliance of
      patients. The study is in progress (14 further patients will be included).

PMID- 15466984
TI  - Robustness of case-control studies of genetic factors to population
      stratification: magnitude of bias and type I error.
AB  - Case-control studies of genetic factors are prone to a special form of
      confounding called population stratification, whenever the existence of one or
      more subpopulations may lead to a false association, be it positive or negative.
      We quantify both the bias (in terms of confounding risk ratio) and the
      probability of false association (type I error) in the most unfavorable situation
      in which only one high-risk subpopulation is hidden within the studied
      population, considering different scenarios of population structuring and varying
      sample sizes. In accord with previous work, we find that the bias is likely to be
      small in most cases. In addition, we show that the same applies to the associated
      type I error whenever the subpopulation is small in proportion. For instance,
      when the hidden subpopulation makes up 5% of the entire population, with an
      allelic frequency of 0.25 (versus 0.10) and a disease rate that is double, then
      the estimated bias is 1.07 and the type I error associated with a sample of 500
      cases and 500 controls is 8% (instead of 5%). We also show that the type I error
      is substantially greater for a rare allele (frequency of 0.1) than for a common
      allele (frequency of 0.5) and analyze the pattern of increase of vulnerability to
      stratification bias with sample size. Based on our findings, we may therefore
      conclude that with moderate sample sizes the type I error associated with
      population stratification remains very limited in most realistic scenarios.

PMID- 15466985
TI  - Dietary factors and risk of non-Hodgkin lymphoma by histologic subtype: a case
      control analysis.
AB  - There is speculation that etiologic heterogeneity exists among tumors classified
      as non-Hodgkin lymphoma (NHL), although it is not known whether diet-related
      associations vary between tumor subgroups. We analyzed data on 1,642 NHL cases
      and 5,039 controls aged 20 to 74 years from a population-based case-control study
      conducted in eight Canadian provinces to explore associations between dietary
      factors and NHL by histologic subtype. Dietary information was collected using a
      69-item food frequency questionnaire. Tumors were categorized into histologic
      subtypes using the contents of pathology reports from the original
      histopathologic review of diagnostic material. Odds ratios (OR) relating
      consumption of dietary factors (divided into three categories) to each NHL
      subtype (diffuse, follicular, small lymphocytic, high grade, peripheral T cell,
      and unspecified lymphomas) were calculated using polytomous logistic regression.
      We found an increased risk of NHL with high (versus low) intake of processed meat
      (OR, 1.49), cheese (OR, 1.38), eggs (OR, 1.49), and dessert foods (OR, 1.24).
      Positive associations with NHL were also found for high consumption of total fat
      (OR, 1.28), saturated fat (OR, 1.29), and monounsaturated fat (OR, 1.27).
      Associations for consumption of some vegetables and fats were found to differ
      between lymphoma subtypes. Given the large number of diet/subtype comparisons
      done, however, the possibility that this heterogeneity arose by chance cannot be
      ruled out. In conclusion, these findings generally do not support the existence
      of etiologic heterogeneity between histologic subtypes of NHL in their
      associations with components of dietary intake.

PMID- 15466987
TI  - No association between OGG1 Ser326Cys and risk of basal cell carcinoma.

PMID- 15466986
TI  - Interleukin-6 sequence variants are not associated with prostate cancer risk.

PMID- 15466988
TI  - "I read with interest.........".

PMID- 15466990
TI  - Paediatric liver transplantation: the surgical view.
AB  - Liver transplantation is the accepted treatment for a wide variety of liver
      diseases in children. Over the past 10 years a number of innovative surgical
      techniques have been developed to overcome the shortage of size matched donors
      particularly in children less than 5 years of age. Graft and patient survival at
      one year after liver transplantation has continued to improve, and is now over
      85% and higher for good risk cases. Complications are relatively common, but
      provided graft function is satisfactory, long term survival for these children is
      to be expected. The need for retransplantation has fallen significantly. Causes
      of early mortality include graft dysfunction and sepsis. Late mortality is due to
      sepsis, post-transplant lymphoproliferative disease, and non-compliance. Long
      term survival with good graft function and excellent quality of life is possible
      for the majority of children undergoing liver transplantation.

PMID- 15466989
TI  - Gene therapy in clinical medicine.
AB  - Although the field of gene therapy has experienced significant setbacks and
      limited success, it is one of the most promising and active research fields in
      medicine. Interest in this therapeutic modality is based on the potential for
      treatment and cure of some of the most malignant and devastating diseases
      affecting humans. Over the next decade, the relevance of gene therapy to medical
      practices will increase and it will become important for physicians to understand
      the basic principles and strategies that underlie the therapeutic intervention.
      This report reviews the history, basic strategies, tools, and several current
      clinical paradigms for application.

PMID- 15466991
TI  - Justified and unjustified use of growth hormone.
AB  - Growth hormone (GH) replacement therapy for children and adults with proven GH
      deficiency due to a pituitary disorder has become an accepted therapy with proven
      efficacy. GH is increasingly suggested, however, as a potential treatment for
      frailty, osteoporosis, morbid obesity, cardiac failure, and various catabolic
      conditions. However, the available placebo controlled studies have not reported
      many significant beneficial effects, and it might even be dangerous to use
      excessive GH dosages in conditions in which the body has just decided to decrease
      GH actions. GH can indeed induce changes in body composition that are considered
      to be advantageous to GH deficient and non-GH deficient subjects. In contrast to
      GH replacement therapy in GH deficient subjects, however, excessive GH action due
      to GH misuse seems to be ineffective in improving muscle power. Moreover, there
      are no available study data to indicate that the use of GH for non-GH deficient
      subjects should be advocated, especially as animal data suggest that lower GH
      levels are positively correlated with longevity.

PMID- 15466992
TI  - Tuberous sclerosis associated with giant bilateral bleeding angiomyolipomas.

PMID- 15466993
TI  - New drugs for the treatment of epilepsy: a practical approach.
AB  - The availability of new antiepileptic drugs has broadened the spectrum of medical
      treatment options in epilepsy. The new agents, together with established drugs,
      offer substantial choice for doctors treating patients with focal or generalised
      epilepsy. The newer antiepileptic drugs are not necessarily more effective but
      usually better tolerated than the traditional agents, mainly because of
      favourable pharmacokinetic profiles and fewer interactions. Because treatment
      options have increased, drug therapy can now be tailored to the requirements of
      individual patients. Nevertheless, significant safety and efficacy issues
      continue to exist and there is a need for the development of even better agents.
      This review describes the clinical use of the new antiepileptic drugs, but
      focuses in particular on monotherapy, the treatment of generalised seizures,
      teratogenicity, and the cognitive side effect profile of the newer compounds.

PMID- 15466995
TI  - Tumoral calcinosis in end stage renal disease.

PMID- 15466994
TI  - Dengue viral infections.
AB  - Dengue viral infections are one of the most important mosquito borne diseases in
      the world. They may be asymptomatic or may give rise to undifferentiated fever,
      dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome.
      Annually, 100 million cases of dengue fever and half a million cases of DHF occur
      worldwide. Ninety percent of DHF subjects are children less than 15 years of age.
      At present, dengue is endemic in 112 countries in the world. No vaccine is
      available for preventing this disease. Early recognition and prompt initiation of
      appropriate treatment are vital if disease related morbidity and mortality are to
      be limited. This review outlines aspects of the epidemiology of dengue
      infections, the dengue virus and its mosquito vector, clinical features and
      pathogenesis of dengue infections, and the management and control of these
      infections.

PMID- 15466996
TI  - The 12, 24, or is it 26 cranial nerves?
AB  - Many of our perceptions are gained through interpretative organs that we assume
      to be providing objective accounts. Notably, however, neither vision nor hearing
      provide an objective account of reality. This paper challenges the "conventional
      wisdoms" held regarding the optic, auditory, and hypoglossal nerves, and the
      nerves of eye movement.

PMID- 15466997
TI  - Therapeutic impact of percutaneous spinal biopsy in spinal infection.
AB  - OBJECTIVE: To investigate the therapeutic impact of percutaneous spinal biopsy in
      patients with suspected spinal infection. DESIGN AND PATIENTS: A review of the
      case notes and imaging features of 36 patients who underwent percutaneous spinal
      biopsy was performed. From this group 20 patients with a prebiopsy diagnosis of
      spinal osteomyelitis were identified. Management before biopsy was noted
      including the use of antimicrobial therapy. The results of the histology and
      microbiology were noted along with the subsequent diagnosis and management.
      RESULTS: Eight of the 20 patients (40%) had received antibiotics before the
      biopsy. An organism was isolated in 8/20 cases (40%). Of the eight patients on
      antibiotics, two grew an organism (25%), including one case of candida in a
      patient receiving flucloxacillin. Out of 12 patients not on antibiotics there
      were six cases where an organism was isolated (50%). The result of the biopsy led
      to a change in management in seven of the 20 patients (35%). CONCLUSIONS: Many
      clinicians are treating spinal osteomyelitis empirically with antibiotics before
      biopsy, but this reduces the chance of isolating an organism and determining
      antibiotic sensitivity. Despite this biopsy led to a change in management in 35%
      of cases.

PMID- 15466998
TI  - Fibrinolytic activity in Nigerian diabetics.
AB  - Fibrinolytic activity, using euglobulin lysis time (ELT), was assessed in 46
      Nigerians with type 2 diabetes mellitus to study the effect of the disease on
      fibrinolytic component of haemostasis. There were 20 females and 26 males. Fifty
      age matched non-diabetics and apparently healthy Nigerians were similarly studied
      as controls; there were 24 females and 26 males. In the patients, the mean (SD)
      age of the females was 56.7 (12.0) years and mean (SD) ELT was 276.4 (62.2) min;
      the mean age of the males was 55.7 (8.5) years and mean ELT was 303.5 (51.5) min.
      The mean age for female controls was 54.3 (12.6) years and their mean ELT was
      198.3 (37.5) min; the mean age of the male controls was 53.4 (11.0) years and
      mean ELT was 181.6 (39.4) min. There was reduced fibrinolytic activity in
      diabetic Nigerians as revealed by significantly prolonged ELT in diabetic
      patients compared with healthy controls. There was good correlation between the
      blood glucose level and ELT. The observed changes in fibrinolytic activity in
      this study were not affected by duration of illness. The prolonged ELT in the
      diabetic population is an additional risk factor for thromboembolic disorders.
      Fibrinolytic agents may therefore be useful in the management of diabetes
      mellitus.

PMID- 15466999
TI  - Troponin T: how high is high? Relationship and differences between serum cardiac
      markers according to level of creatine kinase and type of myocardial infarction.
AB  - Cardiac troponins have emerged over recent years as the "gold standard" serum
      biochemical marker for the diagnosis and management for patients with acute
      myocardial infarction (MI). The relationship between old (creatine kinase; CK)
      and new (troponin T; TT) markers of myocardial injury were examined in this study
      of 392 consecutive patients admitted to a district hospital with a diagnosis of
      an acute MI. Significant correlation of serum TT and peak CK levels were seen (R
      = 0.58, p<0.0001) in all types of MI. A significant relationship was also seen
      according to type of MI (Q wave or non-Q wave MI) or peak CK level. The
      regression equation (TT (microg/l) = 0.0027 (peak CK) + 1.1160 (IU/l)) may be
      used by clinicians to estimate TT release from a known peak CK result and thus
      provide some guidance on equivalence between the two tests. Our findings provide
      physicians with a benchmark reference range between the two cardiac markers,
      according to level of peak CK.

PMID- 15467000
TI  - Non-attendance at clinic: cycles of audit of a consultant based gastroenterology
      outpatient department.
AB  - Attempts were made to reduce defaulting rates for new appointments to see a
      consultant in a general medical and gastroenterology clinic. Despite optimising
      the operation of the clinic, the non-attendance rate remained unsatisfactory, and
      comparable to the average for the NHS. There were short term improvements in
      defaulting rates, which appeared to result from extraneous factors such as a
      general election and moving to new buildings. Though efforts to improve
      attendance rates seem appropriate to conserve resources, no definite
      recommendations can be made on the results of this study.

PMID- 15467001
TI  - Acute pancreatitis due to ramipril therapy.
AB  - Few data exist about the incidence of drug induced acute pancreatitis in the
      general population. Drugs are related to the aetiology of pancreatitis in about
      1.4%-2% of cases. Although angiotensin converting enzymes are generally well
      tolerated, acute pancreatitis has been reported in a few subjects treated with
      captopril, enalapril, and lisinopril. A 85 year old man with a long standing
      history of hypertension, who was treated with ramipril 5 mg once daily, presented
      with acute pancreatitis. Other causes of the disease were ruled out. After
      cessation of ramipril his condition improved and amylase level decreased. This
      was his third episode of acute pancreatitis since ramipril was started in 2000.
      To the authors' knowledge ramipril induced pancreatitis has not previously been
      reported.

PMID- 15467002
TI  - Infective endocarditis from Enterococcus faecalis complicating colonoscopy in
      Heyde's syndrome.
AB  - A case of infective endocarditis from Enterococcus faecalis after colonoscopy in
      a patient with aortic stenoinsufficiency and bleeding intestinal angiodysplasia
      (Heyde's syndrome) is reported.A 77 year old man with aortic stenoinsufficiency
      presented with enterorrhagia and underwent a colonoscopy, which showed normal
      findings. Fifteen days later he developed a moderate degree of fever. Blood
      cultures were positive for E faecalis. An echocardiogram showed aortic valve
      vegetations, and infective endocarditis was diagnosed and successfully treated by
      antibiotics. Some months later, intestinal bleeding recurred and intestinal
      resection was performed. Histopathology showed angiodysplasia. In patients with
      Heyde's syndrome antibiotic prophylaxis should be considered before colonoscopy.

PMID- 15467003
TI  - On the nature of proteinuria with acute renal injury in patients with chronic
      kidney disease.
AB  - Albuminuria is an excellent marker of cardiovascular and renal prognosis.
      Commercially available tests of immunodetectable albumin in the urine may not
      identify posttranslationally modified albumin that makes it undetectable to
      antibodies. Also, it is unclear whether albumin is degraded to smaller fragments,
      such as through proteolysis, in the course of acute renal injury. In 20 men with
      chronic kidney disease, we measured excretion rates of urinary protein
      (pyragallol red), immundetectable urinary albumin (immunoturbidimetry), and
      urinary total intact albumin (HPLC) after a single dose of 100 mg intravenous
      iron sucrose administered over 5 min. Fragmentation of urinary albumin and
      carbonylation of urinary proteins were assessed by immunoblotting. Results showed
      that iron infusion increased carbonylation of plasma and urinary proteins in a
      time-dependent manner. A transient increase in urinary excretion rates of total
      protein, immunodetectable urinary albumin, and total intact albumin was seen.
      Fragmentation and loss of immunoreactivity of albumin paralleled the changes in
      total protein excretion. In conclusion, fragmentation, loss of immunoreactivity,
      and oxidation of albumin in a time-dependent manner may underestimate the extent
      of injury with the immunoreactive microalbumin assay. Measurement of total intact
      albumin may better quantify acute renal injury.

PMID- 15467004
TI  - Reduced tolerance of immature renal tubules to anoxia by HSF-1 decoy.
AB  - Immature animals demonstrate an amplified heat shock response following a variety
      of insults compared with that seen in mature animals (M). The potential role of
      the heat shock response in modulating immature tolerance to injury was compared
      between rat pups, 10 postnatal days of age (P10), and M. Baseline levels of the
      heat shock transcription factor (HSF-1) were substantially elevated in P10
      compared with M animals. In uninjured P10 pups, HSF-1 level was comparable to
      that of M animals subjected to 45 min of ischemia. As anticipated, the integrity
      of suspensions of tubules exposed to anoxia was preserved in P10 animals (23% LDH
      release) compared with M (40%), P < 0.01. The effect of targeted inhibition of
      HSF-1 on tubular integrity was studied using a cyclic oligonucleotide decoy. The
      HSF-1 decoy increased the severity of anoxic injury in P10 pups to a level
      comparable with M animals. LDH release was 33% in decoy-treated P10 tubules
      compared with 40% in M. When P10 tubules were treated with scrambled decoy,
      resistance to anoxia remained intact (24%). The increased vulnerability of the
      tubular suspension to injury was specific to the HSF-1 decoy and proportional to
      the dose of decoy applied. This study demonstrates maturation in the abundance of
      HSF-1 in the immature rat kidney. The loss of resistance of immature tubules to
      anoxia with specific inhibition of HSF-1 may be due to its effect on the heat
      shock response or other signaling pathways of critical pathobiological importance
      in renal cell injury.

PMID- 15467006
TI  - Megalin binds and internalizes angiotensin II.
AB  - Megalin is an abundant membrane protein heavily involved in receptor-mediated
      endocytosis. The major functions of megalin in vivo remain incompletely defined
      as megalin typically faces specialized milieus such as glomerular filtrate,
      airways, epididymal fluid, thyroid colloid, and yolk sac fluid, which lack many
      of its known ligands. In the course of studies on ANG II internalization, we were
      surprised when only part of the uptake of labeled ANG II into immortalized yolk
      sac cells (BN-16 cells) was blocked by specific peptide inhibitors and direct
      competitors of the angiotensin type 1 receptor. This led us to test if megalin
      was a receptor for ANG II. Four lines of direct evidence demonstrate that megalin
      and, to a lesser extent, its chaperone protein cubilin are receptors for ANG II.
      First, in BN-16 cells anti-megalin and anti-cubilin antisera interfere with ANG
      II uptake. Second, also in BN-16 cells, pure ANG II competes for uptake of a
      known megalin ligand. Third, in proximal tubule cell brush-border membrane
      vesicles extracted from mice, anti-megalin antisera interfere with ANG II
      binding. Fourth, purified megalin binds ANG II directly in surface plasmon
      resonance experiments. The finding that megalin is a receptor for ANG II suggests
      a major new function for the megalin pathway in vivo. These results also indicate
      that ANG II internalization in some tissues is megalin dependent and that megalin
      may play a role in regulating proximal tubule ANG II levels.

PMID- 15467005
TI  - Superoxide scavenging attenuates renal responses to ANG II during nitric oxide
      synthase inhibition in anesthetized dogs.
AB  - To assess the role of superoxide (O2-) and nitric oxide (NO) interaction in
      mediating the renal actions of ANG II, we examined the renal responses to intra
      arterial infusion of ANG II (0.5 ng x kg(-1) x min(-1)) before and during
      administration of a superoxide dismutase mimetic, tempol (0.5 mg x kg(-1) x min(
      1)), in the presence or absence of NO synthase inhibitor, nitro-L-arginine (NLA;
      50 microg x kg(-1) x min(-1)), in anesthetized dogs pretreated with enalaprilat
      (33 microg x kg(-1) x min(-1)). In one group of dogs (n = 7), ANG II infusion
      before tempol infusion caused decreases of 24 +/- 4% in renal blood flow (RBF),
      55 +/- 7% in urine flow (V), and 53 +/- 8% in urinary sodium excretion (U(Na)V)
      with a slight decrease in glomerular filtration rate (GFR; -7.8 +/- 3.4%). Tempol
      infusion alone did not cause significant alterations in RBF, GFR, V, or U(Na)V;
      however, ANG II in the presence of tempol caused a smaller degree of decreases in
      RBF (-12 +/- 2%), in V (-16 +/- 5%), and in U(Na)V (-27 +/- 10%) with a slight
      increase in GFR (6.6 +/- 2.8%) than the responses observed before tempol. In
      another group of NLA-treated dogs (n = 6), tempol infusion also caused
      significant attenuation in the ANG II-induced responses on RBF (-13 +/- 3% vs. 
      22 +/- 7%), GFR (-19 +/- 5% vs. -33 +/- 3), V (-15 +/- 12% vs. -28 +/- 4%), and
      U(Na)V (-11 +/- 14% vs. -32 +/- 7%). These data demonstrate that renal responses
      to ANG II are partly mediated by O2- generation and its interaction with NO. The
      sodium-retaining effect of ANG II is greatly influenced by O2- generation,
      particularly in the condition of NO deficiency.

PMID- 15467007
TI  - The role of angiotensin converting enzyme 2 in the generation of angiotensin 1-7
      by rat proximal tubules.
AB  - ANG converting enzyme (ACE) 2 (ACE2) is a homologue of ACE, which is not blocked
      by conventional ACE inhibitors. ACE2 converts ANG 1-10 (ANG I) to ANG 1-9, which
      can be hydrolyzed by ACE to form the biologically active peptide ANG 1-7. ACE2 is
      expressed in the kidney, but its precise intrarenal localization is unclear, and
      the role of intrarenal ACE2 in the production of ANG 1-7 is unknown. The present
      studies determined the relative distribution of ACE2 in the rat kidney and
      defined its role in the generation of ANG 1-7 in proximal tubule. In
      microdissected rat nephron segments, semiquantitative RT-PCR revealed that ACE2
      mRNA was widely expressed, with relatively high levels in proximal straight
      tubule (PST). Immunohistochemistry demonstrated ACE2 protein in tubular segments,
      glomeruli, and endothelial cells. Utilizing mass spectrometry, incubation of
      isolated PSTs with ANG I (10(-6) M) led to generation of ANG 1-7 (sensitivity of
      detection > 1 x 10(-9) M), accompanied by the formation of ANG 1-8 (ANG II) and
      ANG 1-9. The ACE2 inhibitor DX600 completely blocked ANG I-mediated generation of
      ANG 1-7. Incubation of PSTs with ANG 1-9 also led to generation of ANG 1-7, an
      effect blocked by the ACE inhibitor captopril or enalaprilat, but not by DX600.
      Incubation of PSTs with ANG II or luminal perfusion of ANG II did not result in
      detection of ANG 1-7. The results indicate that ACE2 is widely expressed in rat
      nephron segments and contributes to the production of ANG 1-7 from ANG I in PST.
      ANG II may not be a major substrate for ACE2 in isolated PST. The data suggest
      that ACE2-mediated production of ANG 1-7 represents an important component of the
      proximal tubular renin-ANG system.

PMID- 15467008
TI  - Human cord blood- and bone marrow-derived CD34+ cells regenerate gastrointestinal
      epithelial cells.
AB  - In the present study, we aimed to clarify the capacity of human cord blood- and
      bone marrow-derived progenitor cells to generate gastrointestinal epithelial
      cells in clinical and experimental transplantation settings. First, in a clinical
      transplantation setting, gastrointestinal tissues derived from female pediatric
      or juvenile recipients of allogeneic sex-mismatched bone marrow and cord blood
      transplantation were examined for the presence of donor-derived epithelial cells.
      Gastrointestinal specimens of allogeneic recipients included Y chromosome+
      cytokeratin+ epithelial cells at a frequency of 0.4-1.9%. To further determine
      the capacity of purified human progenitor cells, human cord blood- or bone marrow
      derived CD34+ cells were transplanted into newborn NOD/SCID/beta2
      microglobulin(null) mice as an experimental transplantation assay. When
      gastrointestinal tissues derived from recipient mice were subjected to FISH and
      immunofluorescence analyses, human epithelial cells were identified at a
      frequency of 0.24-0.58% at 3 months posttransplantation. Finally, double FISH
      analyses using species-specific probes revealed that human chromosome+ epithelial
      cells did not possess any murine chromosomes, indicating that donor-derived
      epithelial cells were not generated only by cell fusion. On the basis of these
      findings, it is concluded that purified human cord blood and bone marrow CD34+
      progenitor cells can generate gastrointestinal epithelial cells across allogeneic
      and xenogeneic histocompatibility barriers.

PMID- 15467009
TI  - Transcriptional regulation of the human HFE gene indicates high liver expression
      and erythropoiesis coregulation.
AB  - The human HFE gene is clearly involved in hereditary hemochromatosis, a common
      autosomal recessive genetic disorder of iron homeostasis. However, the precise
      role of the HFE protein is still undefined. Here, to obtain new insight, we
      analyzed the transcriptional regulation of HFE gene and defined the functional
      organization of the HFE promoter. Both in vitro transcription and reporter gene
      assay in transient transfection evidenced a high liver expression of the HFE
      mRNA. The 5' end analysis of mRNA showed two major initiation sites localized at 
      265 and -195 directed by TATA-like sequences and a window of initiation within
      the -120 to -10 GC-rich region upstream of the first coding nucleotide. Positive
      cis-regulating elements were characterized within the -1057/-8 region, and a
      negative one extending upstream (-1485/-1057) was identified. DNase I
      footprinting analysis and gel shift assay revealed several protein binding sites,
      and subsequent functional analysis evidenced transactivation of HFE by liver
      enriched C/EBPalpha, erythropoietic-specific GATA-1, and ubiquitous Sp1
      transcription factors. These data bring some evidence of a role of HFE in the
      liver and a coregulation with erythropoiesis as other genes involved in iron
      homeostasis.

PMID- 15467010
TI  - GTP cyclohydrolase I gene transfer reverses tetrahydrobiopterin deficiency and
      increases nitric oxide synthesis in endothelial cells and isolated vessels from
      diabetic rats.
AB  - Nitric oxide (NO) synthesis in endothelial cells is impaired in diabetes. We
      previously showed that impaired NO synthesis in the spontaneously diabetic BB
      (BBd) rat is due to decreased levels of tetrahydrobiopterin (BH4), secondary to
      decreased expression of GTP cyclohydrolase I (GTPCH). The aim of this study was
      to utilize adenoviral GTPCH gene transfer to reverse BH4 deficiency and repair
      the ability of endothelial cells to produce NO. GTPCH gene transfer increased BH4
      levels in BBd endothelial cells from 0.17 +/- 0.02 (mean +/-SE) to 73.37 +/-
      14.42 pmol/million cells and NO production from 0.77 +/- 0.07 to 18.74 +/- 5.52
      nmol/24 h/million cells. To demonstrate a functional effect of increasing BH4
      concentrations in tissues, we transferred GTPCH into aortic rings from BBd and
      Zucker diabetic fatty (ZDF) rats, models of human type I and type II diabetes,
      respectively. GTPCH gene transfer led to a dose-dependent increase in
      acetylcholine-induced vasorelaxation, preventable by inhibiting NO synthase.
      Maximal relaxation of virus-treated rings (10(10) virus particles/ml) to
      acetylcholine was significantly higher than sham-treated rings (BBd 64% vs. 37%,
      P<0.005; ZDF 80% vs. 44%, P<0.05). This study demonstrates that GTPCH gene
      transfer can reverse BH4 deficiency in both type I and type II diabetes and
      provides an experimental basis for using gene therapy to treat cardiovascular
      complications in diabetic patients.

PMID- 15467011
TI  - Gene expression profiling in chronic copper overload reveals upregulation of Prnp
      and App.
AB  - The level at which copper becomes toxic is not clear. Several studies have
      indicated that copper causes oxidative stress; however, most have tested very
      high levels of copper exposure. We currently have only a limited understanding of
      the protective systems that operate in cells chronically exposed to copper.
      Additionally, the limits of homeostatic regulation are not known, making it
      difficult to define the milder effects of copper excess. Furthermore, a robust
      assay to facilitate the diagnosis of copper excess and to distinguish mild,
      moderate, and severe copper overload is needed. To address these issues, we have
      investigated the effects on steady-state gene expression of chronic copper
      overload in a cell culture model system using cDNA microarrays. For this study we
      utilized cells from genetic models of copper overload: fibroblast cells from two
      mouse mutants, C57BL/6-Atp7a(Mobr) and C57BL/6-Atp7a(Modap). These cell lines
      accumulate copper to abnormally high levels in normal culture media due to a
      defect in copper export from the cell. We identified 12 differentially expressed
      genes in common using our outlier identification methods. Surprisingly, our
      results show no evidence of oxidative stress in the copper-loaded cells. In
      addition, candidate components perhaps responsible for a copper-specific
      homeostatic response are identified. The genes that encode for the prion protein
      and the amyloid-beta precursor protein, two known copper-binding proteins, are
      upregulated in both cell lines.

PMID- 15467012
TI  - Layer-specific differences of gene expression in extraocular muscles identified
      by laser-capture microscopy.
AB  - In mammals, separate muscles are typically specialized as a whole to provide
      distinct functional roles leading to well-recognized adaptations. This is
      exemplified in the lower limb by the slow, fatigue-resistant soleus, which
      provides a postural role vs. the fast, fatiguable tibialis anterior (TA), which
      provides rapid movements. A unique characteristic of extraocular muscles (EOMs)
      is their compartmentalization into two distinct layers, the orbital layer (OL)
      and global layer (GL), presumably to subserve diverse functions within the same
      muscle. However, molecular evidence of this diversity has been limited. We used
      laser-capture microscopy coupled with microarray-based expression profiling to
      identify molecular differences between the OL and GL of rat EOMs. We found that
      210 genes were differentially regulated between these layers at a twofold
      expression cutoff. Differences in genes related to metabolic pathways and related
      to structural elements of muscle and nerve formed the largest functional
      clusters. Layer-specific differential expression was validated at both mRNA and
      protein level for MYH3, MYH6, and ACTN3. The expected layer-specific differences
      among genes encoding vascular elements were not evident by profiling;
      morphometric analysis demonstrated that the differences exist, but at a magnitude
      below the cutoff level established by our statistical methods. Comparison of
      these results with previous results comparing whole EOMs and TA suggest
      evolutionary mechanisms may play a role in achieving functional distinctions
      between OL and GL.

PMID- 15467013
TI  - Target ablation-induced regulation of macrophage recruitment into the olfactory
      epithelium of Mip-1alpha-/- mice and restoration of function by exogenous MIP
      1alpha.
AB  - The chemokine macrophage inflammatory protein (MIP)-1alpha recruits macrophages
      to sites of epithelial remodeling. We showed previously that mRNA and protein
      levels of MIP-1alpha in the olfactory epithelium (OE) increased significantly at
      3 days after bilateral olfactory bulbectomy (OBX). The first aim of this study
      was to investigate the effect of the absence of MIP-1alpha on macrophage
      recruitment to the OE 3 days after OBX in Mip-1alpha(-/-) mice compared with
      C57BL/6 mice and to test whether chemokine function could be restored by MIP
      1alpha protein injection into Mip-1alpha(-/-) mice. OBX was performed on C57BL/6
      and Mip-1alpha(-/-) mice. The mice received six subcutaneous injections at 12-h
      intervals of either 10 mug/ml MIP-1alpha protein in carrier or carrier only.
      Macrophage recruitment was evaluated with antibodies to CD68 for all macrophages
      and F4/80 for activated macrophages. Compared with C57BL/6 mice, at 3 days post
      OBX the numbers of CD68(+) and F4/80(+) macrophages were significantly lower in
      carrier-injected Mip-1alpha(-/-) mice and were comparable in MIP-1alpha protein
      injected Mip-1alpha(-/-) mice. The second aim was to determine the identity of
      genes regulated at 3 days post-OBX in the OE of carrier-injected Mip-1alpha(-/-)
      mice compared with carrier-injected C57BL/6 mice. Total RNA from the OE was
      hybridized to Affymetrix microarrays. A number of chemokine-, cytokine-, and
      growth factor-related genes were significantly regulated in the Mip-1alpha(-/-)
      mice and were restored in MIP-1alpha protein-injected Mip-1alpha(-/-) mice. The
      results illustrated that MIP-1alpha played a key role in recruitment of
      macrophages to the OE and provided insight into the genomic regulation involved
      in OE remodeling.

PMID- 15467014
TI  - Mechanical stretch is a highly selective regulator of gene expression in human
      bladder smooth muscle cells.
AB  - Application of mechanical stimuli has been shown to alter gene expression in
      bladder smooth muscle cells (SMC). To date, only a limited number of "stretch
      responsive" genes in this cell type have been reported. We employed
      oligonucleotide arrays to identify stretch-sensitive genes in primary culture
      human bladder SMC subjected to repetitive mechanical stimulation for 4 h.
      Differential gene expression between stretched and nonstretched cells was
      assessed using Significance Analysis of Microarrays (SAM). Expression of 20 out
      of 11,731 expressed genes ( approximately 0.17%) was altered >2-fold following
      stretch, with 19 genes induced and one gene (FGF-9) repressed. Using real-time RT
      PCR, we tested independently the responsiveness of 15 genes to stretch and to
      platelet-derived growth factor-BB (PDGF-BB), another hypertrophic stimulus for
      bladder SMC. In response to both stimuli, expression of 13 genes increased, 1
      gene (FGF-9) decreased, and 1 gene was unchanged. Six transcripts (HB-EGF, BMP-2,
      COX-2, LIF, PAR-2, and FGF-9) were evaluated using an ex vivo rat model of
      bladder distension. HB-EGF, BMP-2, COX-2, LIF, and PAR-2 increased with bladder
      stretch ex vivo, whereas FGF-9 decreased, consistent with expression changes
      observed in vitro. In silico analysis of microarray data using the FIRED
      algorithm identified c-jun, AP-1, ATF-2, and neurofibromin-1 (NF-1) as potential
      transcriptional mediators of stretch signals. Furthermore, the promoters of 9 of
      13 stretch-responsive genes contained AP-1 binding sites. These observations
      identify stretch as a highly selective regulator of gene expression in bladder
      SMC. Moreover, they suggest that mechanical and growth factor signals converge on
      common transcriptional regulators that include members of the AP-1 family.

PMID- 15467015
TI  - Differential modulation of baroreflex control of heart rate by neuron- vs. glia
      derived angiotensin II.
AB  - We developed transgenic mice with targeted expression of human renin (hREN) and
      human angiotensinogen (hAGT) to either neurons (N-AII mice) or glia (G-AII mice)
      to test the hypothesis that neuronal and glial ANG II may have differential
      function. Since baseline blood pressure (BP) did not differ between the models
      (109 +/- 3 vs. 114 +/- 4 mmHg), we stressed the BP regulatory pathway by
      measuring the heart rate (HR) (baroreflex) response to phenylephrine- and
      nitroprusside-induced changes in arterial BP. The midpoint of the baroreflex
      curve (BP50) was reset to a significantly higher BP in N-AII mice (131 +/- 5
      mmHg) compared with littermate controls (115 +/- 3 mmHg). Baroreflex gain (slope
      of BP-HR relation) was similar in N-AII and control mice (12 +/- 1 vs. 14 +/- 2
      beats x min(-1) x mmHg(-1)). In contrast, G-AII mice exhibited less of an
      increase in BP50 (125 +/- 5 mmHg) but a larger decrease in baroreflex gain (8 +/-
      1 beats x min(-1) x mmHg(-1)) compared with both control and N-AII mice.
      Differences in BP50 and gain between N-AII, G-AII, and control mice persisted
      after parasympathetic blockade with atropine but were eliminated after
      sympathetic blockade with propranolol, indicating the effects of ANG II were
      selective for cardiosympathetic arm of the reflex. ANG II-like immunoreactivity
      was observed more prominently around the paraventricular nucleus and nucleus
      tractus solitarii in G-AII mice but more prominently in the ventrolateral medulla
      in N-AII mice. We conclude that ANG II differentially modulates baroreflex
      control of HR in mice producing ANG II in neurons vs. glia, and its differential
      function may reflect regional differences in the production of ANG II in
      cardiovascular control nuclei of the brain.

PMID- 15467016
TI  - Coadministration therapy in hypercholesterolemia: a novel approach to achieving
      lipid goals--introduction.

PMID- 15467017
TI  - Pathophysiology of coronary heart disease: a brief review.
AB  - Coronary heart disease (CHD) remains a persistent public health burden in the
      United States, and it is the cause of one of every five deaths each year. The
      link between lipids and CHD has been firmly established, first by epidemiologic
      studies and, more recently, by long-term outcomes trials that demonstrated that
      lowering low-density lipoprotein cholesterol (LDL-C) levels significantly reduced
      the risk of major coronary events. Based on this evidence, the National
      Cholesterol Education Program recommends lowering the LDL-C level to reduce CHD
      risk, particularly for patients at highest risk. Recently, evidence has emerged
      that suggests that C-reactive protein may be a mediator of atherosclerosis and
      its presence may be indicative of increased risk of CHD. Although these data are
      intriguing, their relevance has yet to be established in prospective outcomes
      trials. Until then, lipid lowering through lifestyle modification and the use of
      safe and effective modes of therapy should be the emphasis of CHD risk reduction
      strategies.

PMID- 15467018
TI  - Reducing the risk of coronary heart disease via lipid reduction.
AB  - Elevated low-density lipoprotein cholesterol (LDL-C) is closely associated with
      an increased risk of cardiovascular morbidity and mortality. Results from
      numerous well-designed clinical trials indicate that interventions designed to
      modify lipid levels significantly reduce the risk of coronary heart disease
      (CHD), particularly in patients at highest risk. The National Cholesterol
      Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines recommend
      matching the intensity of lipid-lowering therapy to the patient's risk of CHD.
      However, despite the existence of evidence-based treatment guidelines and the
      availability of many safe and effective lipid-modifying modes of therapy, optimal
      CHD risk reduction rarely is achieved.

PMID- 15467019
TI  - Utility of currently available modes of therapy in reaching lipid goals.
AB  - The National Cholesterol Education Program Adult Treatment Panel III lipid
      management guidelines emphasize the importance of matching the intensity of lipid
      modification therapy to each patient's risk of coronary heart disease. For many
      patients who are at low risk, nonpharmacologic interventions such as diet,
      exercise, and smoking cessation can be effective lipid-lowering strategies.
      However, many patients require the addition of drug therapy to achieve lipid
      targets. Currently available lipid-modifying drugs include bile acid
      sequestrants, fibrates, nicotinic acid, cholesterol absorption inhibitors, and
      statins. In addition, nonprescription agents such as plant stanols and sterols
      are available to modify plasma lipid levels. These agents can be used
      individually or coadministered to achieve lipid goals.

PMID- 15467020
TI  - Coadministration of multidrug therapy to achieve lipid goals.
AB  - Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are the drug
      of first choice for lowering low-density lipoprotein cholesterol (LDL-C) levels
      and reducing risk of coronary heart disease (CHD). Current therapeutic use of
      statins, however, has resulted in only a small percentage of patients reaching
      their LDL-C treatment goal. Despite the clinical trial data supporting early
      aggressive use of statins, prescribing physicians are more likely to use lower
      doses of statins, leaving many patients at high risk of CHD short of goals. The
      barrier to achieving cholesterol treatment goals does not appear to be the
      decision to initiate statin therapy, but the failure of prescribers to titrate
      statin therapy to a dose sufficient to achieve goals. An alternative to statin
      monotherapy is coadministration of a statin and a second agent that has a
      different mechanism of action. This approach can increase the likelihood of
      achieving target lipid levels and may be more acceptable to physicians. The
      coadministration of ezetimibe and simvastatin reduces cholesterol derived from
      both endogenous and exogenous sources. Simvastatin reduces the hepatic production
      of cholesterol, and ezetimibe decreases the intestinal absorption of dietary and
      biliary free cholesterol. The coadministration of low doses of these agents has
      been proved to be as effective as high-dose statin therapy in reducing LDL-C
      levels and assisting patients achieve their treatment goals.

PMID- 15467021
TI  - Commentary: vitamin D receptor polymorphism and bone mineral density: effect size
      in Caucasians means detection is uncertain in small studies.

PMID- 15467022
TI  - Outcome prediction and the future of the TNM staging system.

PMID- 15467023
TI  - Despite positive studies, popularity of chemoprevention drugs increasing slowly.

PMID- 15467024
TI  - Money matters: how cost-effectiveness studies are done.

PMID- 15467025
TI  - Experts debate message sent by increased cancer survival rates.

PMID- 15467026
TI  - Stat bite: Number of cancer survivors by sex and years since diagnosis, 2001.

PMID- 15467027
TI  - What's in a name: who is a cancer survivor?

PMID- 15467028
TI  - Proposal for public archive draws support, criticism.

PMID- 15467029
TI  - Clinical trial accrual efforts: some progress amid ongoing debate.

PMID- 15467030
TI  - Colon cancer survival rates with the new American Joint Committee on Cancer sixth
      edition staging.
AB  - BACKGROUND: The recently revised American Joint Committee on Cancer (AJCC) sixth
      edition cancer staging system increased the stratification within colon cancer
      stages II and III defined by the AJCC fifth edition system. Using nationally
      representative Surveillance, Epidemiology, and End Results (SEER) data, we
      compared survival rates associated with colon cancer stages defined according to
      both AJCC systems. METHODS: Using SEER data (from January 1, 1991, through
      December 31, 2000), we identified 119,363 patients with colon adenocarcinoma and
      included all patients in two analyses by stages defined by AJCC fifth and sixth
      edition systems. Tumors were stratified by SEER's "extent of disease" and "number
      of positive [lymph] nodes" coding schemes. Kaplan-Meier analyses were used to
      compare overall and stage-specific 5-year survival. All statistical tests were
      two-sided. RESULTS: Overall 5-year survival was 65.2%. According to stages
      defined by the AJCC fifth edition system, 5-year stage-specific survivals were
      93.2% for stage I, 82.5% for stage II, 59.5% for stage III, and 8.1% for stage
      IV. According to stages defined by the AJCC sixth edition system, 5-year stage
      specific survivals were 93.2% for stage I, 84.7% for stage IIa, 72.2% for stage
      IIb, 83.4% for stage IIIa, 64.1% for stage IIIb, 44.3% for stage IIIc, and 8.1%
      for stage IV. Under the sixth edition system, 5-year survival was statistically
      significantly better for patients with stage IIIa colon cancer (83.4%) than for
      patients with stage IIb disease (72.2%) (P<.001). CONCLUSIONS: The AJCC sixth
      edition system for colon cancer stratifies survival more distinctly than the
      fifth edition system by providing more substages. The association of stage IIIa
      colon cancer with statistically significantly better survival than stage IIb in
      the new system may reflect current clinical practice, in which stage III patients
      receive chemotherapy but stage II patients generally do not.

PMID- 15467031
TI  - Alkylaniline-hemoglobin adducts and risk of non-smoking-related bladder cancer.
AB  - BACKGROUND: Some members of the arylamine family of compounds, specifically 4
      aminobiphenyl (ABP), 2-naphthylamine, and benzidine, are established human
      bladder carcinogens. Cigarette smoking and use of permanent hair dye contribute
      substantially to current arylamine exposure. Low levels of 4-ABP exposure have
      been associated with non-smoking-related bladder cancer. Other arylamine
      compounds coming from as yet unidentified environmental sources may also be human
      bladder carcinogens. METHODS: We conducted a population-based case-control study
      in Los Angeles County, California, involving 298 case subjects with bladder
      cancer and 308 control subjects, who were matched on age, sex, race/ethnicity,
      and neighborhood of residence. In-person interviews provided information on
      tobacco smoking and other potential risk factors for bladder cancer. To assess
      arylamine exposure, levels of arylamine-hemoglobin adducts of nine selected
      alkylanilines (2,3-dimethylaniline [2,3-DMA], 2,4-DMA, 2,5-DMA, 2,6-DMA, 3,4-DMA,
      3,5-DMA, 2-ethylaniline [2-EA], 3-EA, 4-EA) were measured in peripheral blood
      collected from study subjects. Analysis of covariance and conditional logistic
      regression methods were used to analyze the relationship between arylamine
      hemoglobin adducts and bladder cancer risk. All statistical tests were two-sided.
      RESULTS: Levels of all arylamine-hemoglobin adducts, with the exception of 2,6
      DMA, were higher in smokers than in nonsmokers, and levels of all arylamine
      hemoglobin adducts were higher in case subjects than in control subjects.
      Arylamine-hemoglobin adducts of 2,6-DMA, 3,5-DMA, and 3-EA were all
      independently, statistically significantly (all P<.001) associated with bladder
      cancer risk after adjusting for cigarette smoking at the time of blood
      collection, lifetime smoking history, and other potential risk factors. These
      adducts were also independently associated with bladder cancer risk when only
      nonsmokers at time of blood draw were considered (highest quartile versus lowest
      quartile: 2,6-DMA, relative risk [RR] of bladder cancer = 8.1, 95% confidence
      interval [CI] = 3.6 to 18.0; 3,5-DMA, RR = 2.7, 95% CI = 1.2 to 6.0; 3-EA, RR =
      4.3, 95% CI = 1.6 to 11.6). CONCLUSIONS: Diverse arylamine exposures are strongly
      associated with bladder cancer risk among nonsmokers. Because arylamines may
      account for a substantial proportion of bladder cancers among the general
      population, identification of environmental sources of these compounds is needed.

PMID- 15467032
TI  - Factors contributing to mammography failure in women aged 40-49 years.
AB  - BACKGROUND: Younger women (40-49 years) have lower mammographic sensitivity
      (i.e., greater proportion of cancers detected after a negative mammogram) than
      older women (> or =50 years). We explored the effect of tumor growth rate, breast
      density, mammographic image quality, and breast cancer risk factors on
      mammographic sensitivity in younger and older women. METHODS: We studied 576
      women (n = 73 aged 40-49 years and n = 503 aged 50 years or older) who were
      diagnosed with invasive breast cancer between 1988 and 1993. Interval cancers
      were defined as those diagnosed within 12 or 24 months after a negative screening
      mammogram and before a subsequent mammogram. Tumor growth rate was assessed by
      mitotic figure count and Ki-67 positivity. The main outcome measures were
      percentage of women with interval cancer (1 -mammographic sensitivity) by age,
      odds ratio (OR) of interval cancer by age, and excess odds (i.e., the percentage
      of the odds ratio for age that was explained by individual covariates). RESULTS:
      Interval cancers occurred in 27.7% of younger women and 13.9% of older women
      within 12 months (OR = 2.36, 95% confidence interval [CI] = 1.14 to 4.77) and in
      52.1% of younger women and 24.7% of older women within 24 months (OR = 3.58, 95%
      CI = 2.15 to 5.97). Greater breast density explained 67.6% of the decreased
      mammographic sensitivity in younger women at 12 months, whereas rapid tumor
      growth explained 30.6% and breast density explained 37.6% of the decreased
      sensitivity in younger women at 24 months. CONCLUSIONS: Breast density largely
      explained decreased mammographic sensitivity at 12 months, whereas rapid tumor
      growth contributed to decreased mammographic sensitivity at 24 months. A 12-month
      versus a 24-month mammography screening interval may therefore reduce the adverse
      impact of faster growing tumors on mammographic sensitivity in younger women.

PMID- 15467033
TI  - A molecular genetic and statistical approach for the diagnosis of dual-site
      cancers.
AB  - BACKGROUND: Concurrent tumors can be synchronous, independently derived, non
      metastatic tumors or metastatic tumors. The prognosis and clinical management of
      patients with these different concurrent tumor types are different. METHODS: DNA
      from normal and tumor tissues of 62 patients with synchronous endometrial and
      ovarian, bilateral ovarian, or endometrial and bilateral ovarian tumors was
      analyzed for loss of heterozygosity and microsatellite instability using eight
      polymorphic microsatellite markers at loci frequently deleted in ovarian and/or
      endometrial cancers. A statistical algorithm was designed to assess the clonal
      relationship between the tumors. RESULTS: The original histopathology reports
      classified 26 (42%) case patients with single primary tumors and related
      metastatic lesions and 21 (34%) with independent primary tumors; 15 (24%) were
      unclassified. Genetic data identified 35 (56%) case patients with single primary
      tumors and related metastatic lesions, 18 (29%) with independent primary tumors,
      and nine (15%) that could not be typed. Excluding case patients with
      histopathology reports for which a clonal relationship was uncertain or was not
      reported, there was 53% concordance between genetic and histopathology diagnoses.
      Increasing the stringency of the statistical analysis increased the number of
      uncertain diagnoses but did not affect the proportion of discordant genetic and
      histologic diagnoses. CONCLUSIONS: We have developed a rapid and robust combined
      genetic and statistical method to establish whether multiple tumors from the same
      patient represent distinct primary tumors or whether they are clonally related
      and therefore metastatic. For the majority of case patients, histopathology
      reports and genetic analyses were in agreement and diagnostic confidence was
      improved. Importantly, in approximately one-fourth of all case patients, genetic
      and histopathologic analyses suggested alternative diagnoses. The results suggest
      that genetic analysis has implications for clinical management and can be
      performed rapidly as a diagnostic test with paraffin-embedded tissues.

PMID- 15467035
TI  - Predicting resistance or response to chemotherapy by proton magnetic resonance
      spectroscopy in neuroblastoma.
AB  - BACKGROUND: We previously showed that proton magnetic resonance spectroscopy (1H
      MRS) enables estimation of neuroblastoma tumor viability. Here we investigated if
      1H-MRS can predict response or resistance to chemotherapy in neuroblastoma.
      METHODS: Neuroblastoma cell lines with various drug sensitivities were treated
      with cytotoxic drugs (cisplatin, etoposide, and irinotecan) and examined by 1H
      MRS. Viability was assessed by trypan blue staining and the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Nude rats carrying
      drug-sensitive or drug-resistant neuroblastoma xenografts were treated for 4 days
      with irinotecan (n = 11) or saline (n = 11) and were examined with 1H-MRS at 4.7
      T before and during treatment. The Wilcoxon matched-pairs test was used to test
      statistical significance of difference within treatment groups. Independent
      groups were compared using the Mann-Whitney U test. Correlation was assessed with
      Spearman's rank correlation. All statistical tests were two-sided. RESULTS:
      Cytotoxic drug treatment of drug-sensitive SH-SY5Y neuroblastoma cells resulted
      in increased methylene and polyunsaturated fatty acid resonances and decreased
      choline resonance. The methylene/choline ratio correlated with cell death (r(s) =
      .94, P<.001) and was increased in cisplatin-treated drug-sensitive (SH-SY5Y, IMR
      32) but not drug-resistant [SK-N-BE2, SK-N-FI, SK-N-AS] cell lines. No changes
      were observed in SK-N-BE2 cells treated with irinotecan or cisplatin, whereas
      circumvention of the resistance by arsenic trioxide treatment led to lipid
      accumulation and choline depletion. Irinotecan therapy of rats carrying drug
      sensitive xenografts caused the methylene/choline ratio of tumors to increase
      eightfold after 3 days (95% confidence interval [CI] = fivefold to 12-fold; P =
      .005 compared with pretreatment spectra at day 0) and caused tumors to regress
      statistically significantly on day 10 compared with pretreatment volume on day 0
      (difference = -60%, 95% CI = -12% to -100%, n = 6; P = .012). The
      methylene/choline ratio of nonregressing drug-resistant xenografts was
      unaffected. No differences were observed after saline treatment. CONCLUSIONS:
      Response or resistance to chemotherapy is accurately predicted by 1H-MRS in
      experimental neuroblastoma models in vivo.

PMID- 15467034
TI  - Selective efficacy of depsipeptide in a xenograft model of Epstein-Barr virus
      positive lymphoproliferative disorder.
AB  - BACKGROUND: Immune-compromised individuals are at increased risk for developing
      aggressive Epstein-Barr virus (EBV)-associated lymphoproliferative disorders
      after primary EBV infection or for reactivation of a preexisting latent EBV
      infection. We evaluated the effect of depsipeptide, a histone deacetylase
      inhibitor, on EBV-positive lymphoblastoid cell lines (LCLs) and Burkitt lymphoma
      cell lines in a mouse model and explored its mechanism of action in vitro.
      METHODS: We studied EBV-transformed LCLs, which express a latent III (Lat-III)
      viral gene profile, as do some EBV-positive lymphoproliferative malignancies, and
      Burkitt lymphoma cell lines, which express a Lat-I viral gene profile. Cell lines
      were used to characterize depsipeptide-induced apoptosis, which was evaluated by
      flow cytometry. Flow cytometry, western blot analyses, and histone deacetylase
      inhibitors were used to investigate components of prodeath and survival pathways
      in vitro. We studied depsipeptide's effects on survival with a mouse xenograft
      model of EBV-positive human B-cell tumors (groups of 10 mice). All statistical
      tests were two-sided. RESULTS: Depsipeptide (5 mg/m2 of body surface area)
      treatment was associated with statistically significantly improved survival of
      mice carrying Lat-III EBV-positive LCL tumors, compared with that of control
      treated mice (day 30: for depsipeptide-treated mice, 90% survival, 95% confidence
      interval [CI] = 73.2% to 100%; for control-treated mice, 20% survival, 95% CI =
      5.79% to 69.1%; P<.001), but it was not associated with survival of mice carrying
      Lat-I EBV-positive Burkitt lymphoma tumors. Depsipeptide induced apoptosis in 64%
      of LCLs and in 14% of EBV-positive Burkitt lymphoma cells in vitro. Depsipeptide
      treated LCL cultures had two distinct cell populations--one sensitive and one
      resistant to depsipeptide. Depsipeptide-mediated apoptosis was associated with a
      12-fold increased level of active caspase 3, but some apoptosis persisted despite
      z-VAD-fmk treatment to inhibit caspase activity. Depsipeptide-resistant LCLs
      expressed higher levels of latent membrane protein 1 (LMP1; P = .017), BCL2 (P =
      .032), and nuclear factor kappaB (NF-kappaB) (P<.001) than depsipeptide-sensitive
      LCLs; this resistance was circumvented by treatment with PS-1145, an inhibitor of
      NF-kappaB activation (P<.001). CONCLUSIONS: Apoptosis is induced by depsipeptide
      via caspase-dependent and -independent pathways in Lat-III EBV-positive LCLs and
      is enhanced by inhibiting NF-kappaB activity. Depsipeptide as a treatment for Lat
      III EBV-associated lymphoproliferative disorders should be explored further in
      clinical trials.

PMID- 15467036
TI  - Mammographic density and breast cancer after ductal carcinoma in situ.
AB  - Women with ductal carcinoma in situ (DCIS) are at substantially increased risk
      for a second breast cancer, but few strong predictors for these subsequent tumors
      have been identified. We used Cox regression modeling to examine the association
      between mammographic density at diagnosis of DCIS of 504 women from the National
      Surgical Adjuvant Breast and Bowel Project B-17 trial and risk of subsequent
      breast cancer events. In this group of patients, mostly 50 years old or older,
      approximately 6.6% had breasts categorized as highly dense (i.e., > or =75% of
      the breast occupied by dense tissue). After adjusting for treatment with
      radiotherapy, age, and body mass index, women with highly dense breasts had 2.8
      (95% confidence interval [CI] = 1.3 to 6.1) times the risk of subsequent breast
      cancer (DCIS or invasive), 3.2 (95% CI = 1.2 to 8.5) times the risk of invasive
      breast cancer, and 3.0 (95% CI = 1.2 to 7.5) times the risk of any ipsilateral
      breast cancer, compared with women with less than 25% of the breast occupied by
      dense tissue. Our results provide initial evidence that the risk of second breast
      cancers may be increased among DCIS patients with highly dense breasts.

PMID- 15467037
TI  - Effects of angiogenesis inhibitors on vascular network formation by human
      endothelial and melanoma cells.
AB  - Endothelial cells involved in vasculogenesis and angiogenesis are key targets in
      cancer therapy. Recent evidence suggests that tumor cells can express some genes
      typically expressed by endothelial cells and form extracellular matrix-rich
      tubular networks, phenomena known as vasculogenic mimicry. We examined the
      effects of three angiogenesis inhibitors (i.e., anginex, TNP-470, and endostatin)
      on vasculogenic mimicry in human melanoma MUM-2B and C8161 cells and compared
      them with their effects in human endothelial HMEC-1 and HUVEC cells. Anginex, TNP
      470, and endostatin markedly inhibited vascular cord and tube formation by HMEC-1
      and HUVEC cells in vitro, whereas tubular network formation by MUM-2B and C8161
      cells was relatively unaffected. Endothelial cells expressed higher mRNA and
      protein levels for two putative endostatin receptors, alpha5 integrin and heparin
      sulfate proteoglycan 2, than melanoma cells, suggesting a mechanistic basis for
      the differential response of the two cell types to angiogenesis inhibitors. These
      findings may contribute to the development of new antivascular therapeutic agents
      that target both angiogenesis and tumor cell vasculogenic mimicry.

PMID- 15467038
TI  - Re: Polymorphisms of death pathway genes FAS and FASL in esophageal squamous-cell
      carcinoma.

PMID- 15467039
TI  - Re: Long-term efficacy of zoledronic acid for the prevention of skeletal
      complications in patients with metastatic hormone-refractory prostate cancer.

PMID- 15467040
TI  - A piece of my mind. Spectre of Noah: "tell me a story!".

PMID- 15467041
TI  - Navigating the body's water channels, scientists gain insights into disease.

PMID- 15467042
TI  - Military psychiatrists strive to quell soldiers' nightmares of war.

PMID- 15467043
TI  - When military parents are sent to war, children left behind need ample support.

PMID- 15467048
TI  - Natural history of early localized prostate cancer.

PMID- 15467049
TI  - Natural history of early localized prostate cancer.

PMID- 15467050
TI  - Cervical cancer screening among women without a cervix.

PMID- 15467051
TI  - Cervical cancer screening among women without a cervix.

PMID- 15467052
TI  - Cervical cancer screening among women without a cervix.

PMID- 15467053
TI  - Cervical cancer screening among women without a cervix.

PMID- 15467054
TI  - Fetal microchimeric cells and breast cancer.

PMID- 15467055
TI  - Estimating prognosis for nursing home residents with advanced dementia.

PMID- 15467056
TI  - Faux pox: 2 case reports.

PMID- 15467057
TI  - Relationship of blood transfusion and clinical outcomes in patients with acute
      coronary syndromes.
AB  - CONTEXT: It is unclear if blood transfusion in anemic patients with acute
      coronary syndromes is associated with improved survival. OBJECTIVE: To determine
      the association between blood transfusion and mortality among patients with acute
      coronary syndromes who develop bleeding, anemia, or both during their hospital
      course. DESIGN, SETTING, AND PATIENTS: We analyzed 24,112 enrollees in 3 large
      international trials of patients with acute coronary syndromes (the GUSTO IIb,
      PURSUIT, and PARAGON B trials). Patients were grouped according to whether they
      received a blood transfusion during the hospitalization. The association between
      transfusion and outcome was assessed using Cox proportional hazards modeling that
      incorporated transfusion as a time-dependent covariate and the propensity to
      receive blood, and a landmark analysis. MAIN OUTCOME MEASURE: Thirty-day
      mortality. RESULTS: Of the patients included, 2401 (10.0%) underwent at least 1
      blood transfusion during their hospitalization. Patients who underwent
      transfusion were older and had more comorbid illness at presentation and also had
      a significantly higher unadjusted rate of 30-day death (8.00% vs 3.08%; P<.001),
      myocardial infarction (MI) (25.16% vs 8.16%; P<.001), and death/MI (29.24% vs
      10.02%; P<.001) compared with patients who did not undergo transfusion. Using Cox
      proportional hazards modeling that incorporated transfusion as a time-dependent
      covariate, transfusion was associated with an increased hazard for 30-day death
      (adjusted hazard ratio [HR], 3.94; 95% confidence interval [CI], 3.26-4.75) and
      30-day death/MI (HR, 2.92; 95% CI, 2.55-3.35). In the landmark analysis that
      included procedures and bleeding events, transfusion was associated with a trend
      toward increased mortality. The predicted probability of 30-day death was higher
      with transfusion at nadir hematocrit values above 25%. CONCLUSIONS: Blood
      transfusion in the setting of acute coronary syndromes is associated with higher
      mortality, and this relationship persists after adjustment for other predictive
      factors and timing of events. Given the limitations of post hoc analysis of
      clinical trials data, a randomized trial of transfusion strategies is warranted
      to resolve the disparity in results between our study and other observational
      studies. We suggest caution regarding the routine use of blood transfusion to
      maintain arbitrary hematocrit levels in stable patients with ischemic heart
      disease.

PMID- 15467058
TI  - Racial and ethnic differences in time to acute reperfusion therapy for patients
      hospitalized with myocardial infarction.
AB  - CONTEXT: Nonwhite patients experience significantly longer times to fibrinolytic
      therapy (door-to-drug times) and percutaneous coronary intervention (door-to
      balloon times) than white patients, raising concerns of health care disparities,
      but the reasons for these patterns are poorly understood. OBJECTIVES: To estimate
      race/ethnicity differences in door-to-drug and door-to-balloon times for patients
      receiving primary reperfusion for ST-segment elevation myocardial infarction; to
      examine how sociodemographic factors, insurance status, clinical characteristics,
      and hospital features mediate racial/ethnic differences. DESIGN, SETTING, AND
      PATIENTS: Retrospective, observational study using admission and treatment data
      from the National Registry of Myocardial Infarction (NRMI) for a US cohort of
      patients with ST-segment elevation myocardial infarction or left bundle-branch
      block and receiving reperfusion therapy. Patients (73,032 receiving fibrinolytic
      therapy; 37,143 receiving primary percutaneous coronary intervention) were
      admitted from January 1, 1999, through December 31, 2002, to hospitals
      participating in NRMI 3 and 4. MAIN OUTCOME MEASURE: Minutes between hospital
      arrival and acute reperfusion therapy. RESULTS: Door-to-drug times were
      significantly longer for patients identified as African American/black (41.1
      minutes), Hispanic (36.1 minutes), and Asian/Pacific Islander (37.4 minutes),
      compared with patients identified as white (33.8 minutes) (P<.01 for all). Door
      to-balloon times for patients identified as African American/black (122.3
      minutes) or Hispanic (114.8 minutes) were significantly longer than for patients
      identified as white (103.4 minutes) (P<.001 for both). Racial/ethnic differences
      were still significant but were substantially reduced after accounting for
      differences in mean times to treatment for the hospitals in which patients were
      treated; significant racial/ethnic differences persisted after further adjustment
      for sociodemographic characteristics, insurance status, and clinical and hospital
      characteristics (P<.01 for all). CONCLUSION: A substantial portion of the
      racial/ethnic disparity in time to treatment was accounted for by the specific
      hospital to which patients were admitted, in contrast to differential treatment
      by race/ethnicity inside the hospital.

PMID- 15467059
TI  - Estrogen plus progestin and risk of venous thrombosis.
AB  - CONTEXT: Postmenopausal hormone therapy increases the risk of venous thrombosis.
      It is not known whether other factors influencing thrombosis add to this risk.
      OBJECTIVE: To report final data on incidence of venous thrombosis in the Women's
      Health Initiative Estrogen Plus Progestin clinical trial and the association of
      hormone therapy with venous thrombosis in the setting of other thrombosis risk
      factors. DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized controlled
      trial of 16,608 postmenopausal women between the ages of 50 and 79 years, who
      were enrolled in 1993 through 1998 at 40 US clinical centers with 5.6 years of
      follow up; and a nested case-control study. Baseline gene variants related to
      thrombosis risk were measured in the first 147 women who developed thrombosis and
      in 513 controls. INTERVENTION: Random assignment to 0.625 mg/d of conjugated
      equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate, or placebo. MAIN
      OUTCOME MEASURES: Centrally validated deep vein thrombosis and pulmonary embolus.
      RESULTS: Venous thrombosis occurred in 167 women taking estrogen plus progestin
      (3.5 per 1000 person-years) and in 76 taking placebo (1.7 per 1000 person-years);
      hazard ratio (HR), 2.06 (95% confidence interval [CI], 1.57-2.70). Compared with
      women between the ages of 50 and 59 years who were taking placebo, the risk
      associated with hormone therapy was higher with age: HR of 4.28 (95% CI, 2.38
      7.72) for women aged 60 to 69 years and 7.46 (95% CI, 4.32-14.38) for women aged
      70 to 79 years. Compared with women who were of normal weight and taking placebo,
      the risk associated with taking estrogen plus progestin was increased among
      overweight and obese women: HR of 3.80 (95% CI, 2.08-6.94) and 5.61 (95% CI, 3.12
      10.11), respectively. Factor V Leiden enhanced the hormone-associated risk of
      thrombosis with a 6.69-fold increased risk compared with women in the placebo
      group without the mutation (95% CI, 3.09-14.49). Other genetic variants
      (prothrombin 20210A, methylenetetrahydrofolate reductase C677T, factor XIII
      Val34Leu, PAI-1 4G/5G, and factor V HR2) did not modify the association of
      hormone therapy with venous thrombosis. CONCLUSIONS: Estrogen plus progestin was
      associated with doubling the risk of venous thrombosis. Estrogen plus progestin
      therapy increased the risks associated with age, overweight or obesity, and
      factor V Leiden.

PMID- 15467060
TI  - Esterified estrogens and conjugated equine estrogens and the risk of venous
      thrombosis.
AB  - CONTEXT: Clinical trial evidence indicates that estrogen therapy with or without
      progestins increases venous thrombotic risk. The findings from these trials,
      which used oral conjugated equine estrogens, may not be generalizable to other
      estrogen compounds. OBJECTIVE: To compare risk of venous thrombosis among
      esterified estrogen users, conjugated equine estrogen users, and nonusers.
      DESIGN, SETTING, AND PARTICIPANTS: This population-based, case-control study was
      conducted at a large health maintenance organization in Washington State. Cases
      were perimenopausal and postmenopausal women aged 30 to 89 years who sustained a
      first venous thrombosis between January 1995 and December 2001 and controls were
      matched on age, hypertension status, and calendar year. MAIN OUTCOME MEASURE:
      Risk of first venous thrombosis in relation to current use of esterified or
      conjugated equine estrogens, with or without concomitant progestin. Current use
      was defined as use at thrombotic event for cases and a comparable reference date
      for controls. RESULTS: Five hundred eighty-six incident venous thrombosis cases
      and 2268 controls were identified. Compared with women not currently using
      hormones, current users of esterified estrogen had no increase in venous
      thrombotic risk (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.69-1.22).
      In contrast, women currently taking conjugated equine estrogen had an elevated
      risk (OR, 1.65; 95% CI, 1.24-2.19). When analyses were restricted to estrogen
      users, current users of conjugated equine estrogen had a higher risk than current
      users of esterified estrogen (OR, 1.78; 95% CI, 1.11-2.84). Among conjugated
      equine estrogen users, increasing daily dose was associated with increased risk
      (trend P value = .02). Among all estrogen users, concomitant progestin use was
      associated with increased risk compared with use of estrogen alone (OR, 1.60; 95%
      CI, 1.13-2.26). CONCLUSION: Our finding that conjugated equine estrogen but not
      esterified estrogen was associated with venous thrombotic risk needs to be
      replicated and may have implications for the choice of hormones in perimenopausal
      and postmenopausal women.

PMID- 15467061
TI  - Favorable cardiovascular risk profile in young women and long-term risk of
      cardiovascular and all-cause mortality.
AB  - CONTEXT: For women, impact of cardiovascular risk factors measured in young
      adulthood, particularly favorable (low-risk) profile, on mortality has been
      difficult to assess due to low short-term death rates. OBJECTIVE: To assess the
      relationship of baseline coronary risk factor status to mortality from coronary
      heart disease (CHD), cardiovascular diseases (CVDs), and all causes in young
      women. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: A total of
      7302 women aged 18 to 39 years without prior CHD or major electrocardiographic
      abnormalities screened between 1967 and 1973 for the Chicago Heart Association
      Detection Project in Industry. Risk groups were defined using national guidelines
      for values of systolic and diastolic blood pressure, serum cholesterol level,
      body mass index, presence of diabetes, and smoking status. Participants were
      divided into 4 groups: low risk, 0 risk factors high but 1 or more unfavorable, 1
      only risk factor high, and 2 or more risk factors high. MAIN OUTCOME MEASURES:
      All-cause mortality, CHD mortality, and CVD mortality; hazard ratio of outcome
      measures comparing low-risk group with other groups. RESULTS: Only 20% met low
      risk criteria; 59% had high levels of 1 or more risk factors. During an average
      follow-up of 31 years, there were 47 CHD deaths, 94 CVD deaths, and 469 deaths
      from all causes. The age-adjusted CVD death rate per 10,000 person-years was
      lowest for low-risk women and increased with the number of risk factors, ie, 1.5,
      1.7, 5.0, and 9.1 for low-risk; 0, 1, and 2 or more risk factors high,
      respectively. Multivariate-adjusted CVD mortality hazard ratio for low-risk women
      was 0.19 (95% confidence interval, 0.08-0.45) compared with women with 2 or more
      risk factors high. Similar patterns were observed for CHD and all-cause mortality
      and for both blacks and whites. CONCLUSION: For women with favorable levels for
      all 5 major risk factors at younger ages, CHD and CVD are rare; long-term and all
      cause mortality are much lower compared with others.

PMID- 15467062
TI  - Interventions to improve research participants' understanding in informed consent
      for research: a systematic review.
AB  - CONTEXT: Available data suggest that prospective research participants may
      frequently not understand information disclosed to them in the informed consent
      process. Little is known about how understanding can be improved. OBJECTIVE: To
      review research on interventions to improve research participants' understanding
      of information disclosed in the informed consent process. DATA SOURCES AND STUDY
      SELECTION: A search of MEDLINE was performed using the terms informed consent and
      clinical research and informed consent and (comprehension or understanding) from
      1966 to March 2004 , which included randomized controlled trials, longitudinal
      trials, and controlled trials with nonrandom allocation that compared the
      understanding of research participants who had undergone only a standard informed
      consent process to that of participants who had received an intervention to
      improve their understanding. A comprehensive bibliography of empirical research
      on informed consent published in January 1999 was also reviewed, as were personal
      files and all issues of the journals IRB and Controlled Clinical Trials. DATA
      EXTRACTION: Study design, quality criteria, population characteristics,
      interventions, and outcomes for each trial were extracted. The statistical
      significance of the interventions' effects on understanding were noted, as were
      mean scores for understanding for each group of each trial. For those trials that
      measured the secondary outcomes of satisfaction and willingness to enroll,
      results were also summarized. DATA SYNTHESIS: Thirty studies described 42 trials
      that met inclusion criteria. Of 12 trials of multimedia interventions, 3 showed
      significant improvement in understanding. Of 15 trials of enhanced consent forms,
      6 showed significant improvement in understanding (all P<.05), but 5 of 6 trials
      were of limited quality, casting doubt on their practical relevance. Of 5 trials
      of extended discussion, 3 showed significant improvement in understanding (all
      P<.001) and 2 showed trends toward improvement (P=.054 and P=.08). Of 5 trials of
      test/feedback, all showed significant improvement in understanding (all P<.05)
      but were flawed in that they may have mistaken rote memorization for improvement
      in understanding. Another 5 trials were put into a miscellaneous category and had
      varying impact on understanding. Some demographic factors, particularly lower
      education, were associated with less understanding. Satisfaction and willingness
      to enroll were never significantly diminished by an intervention . CONCLUSIONS:
      Efforts to improve understanding through the use of multimedia and enhanced
      consent forms have had only limited success. Having a study team member or a
      neutral educator spend more time talking one-on-one to study participants appears
      to be the most effective available way of improving research participants'
      understanding; however, further research is needed.

PMID- 15467063
TI  - Accuracy of diagnostic tests read with and without clinical information: a
      systematic review.
AB  - CONTEXT: Although it is common practice to read tests with clinical information,
      whether this improves or decreases the accuracy of test reading is uncertain.
      OBJECTIVE: To determine whether diagnostic tests are more accurate when read with
      clinical information or without it. DATA SOURCES: MEDLINE search (1966-December
      2003) extended by search of reference lists and articles citing the articles
      retrieved (Web of Science, 1985-December 2003). STUDY SELECTION: All articles
      comparing the accuracy of tests read twice by the same readers, once without and
      once with clinical information, but otherwise under identical conditions. Only
      articles that reported sensitivity and specificity or receiver operating
      characteristic (ROC) curves were included. DATA EXTRACTION: Data were extracted
      by one author and reviewed independently by the other. When the data were
      difficult to interpret, differences were resolved by discussion. DATA SYNTHESIS:
      Sixteen articles met the inclusion criteria. Eleven articles compared areas under
      ROC curves for tests read with and without clinical information, and 5 compared
      only sensitivity and specificity. Ten articles used actual clinical information;
      6 used constructed clinical information that was plausible. Overall, clinical
      information improved test reading accuracy although the effect was smaller in the
      articles using actual clinical information when compared with those using
      constructed clinical information. There were no instances in which clinical
      information resulted in significant reduction in test reading accuracy. In some
      instances, improved test reading accuracy came from improved sensitivity without
      loss of specificity. CONCLUSIONS: At least for the tests examined, the common
      practice of reading diagnostic tests with clinical information seems justified.
      Future studies should be designed to investigate the best way of providing
      clinical information. These studies should also give an estimate of the accuracy
      of clinical information used, display ROC curves with identified data points, and
      include a wider range of diagnostic tests.

PMID- 15467064
TI  - Do transfusions get to the heart of the matter?

PMID- 15467065
TI  - Measuring race and ethnicity: why and how?

PMID- 15467066
TI  - JAMA patient page. Blood transfusion.

PMID- 15467067
TI  - Before birth--after death.

PMID- 15467068
TI  - The role of medical imaging in the abortion debate.

PMID- 15467069
TI  - The discrepancy between the legal definition of capacity and the British Medical
      Association's guidelines.

PMID- 15467070
TI  - The convention on human rights and biomedicine and the use of coercion in
      psychiatry.
AB  - According to a recent convention on human rights and biomedicine, coercive
      treatment of psychiatric patients may only be given if, without such treatment,
      serious harm is likely to result to the health of the patient; it must not be
      given in the interest of other people. In the present article a discussion is
      undertaken about the implication of this stipulation for the use of coercion in
      psychiatry in general and in forensic psychiatry in particular.

PMID- 15467071
TI  - The right not to know: an autonomy based approach.
AB  - The emerging international biomedical law tends to recognise the right not to
      know one's genetic status. However, the basis and conditions for the exercise of
      this right remain unclear in domestic laws. In addition to this, such a right has
      been criticised at the theoretical level as being in contradiction with patient's
      autonomy, with doctors' duty to inform patients, and with solidarity with family
      members. This happens especially when non-disclosure poses a risk of serious harm
      to the patient's relatives who, without that vital information, could be deprived
      of preventive or therapeutic measures. This paper argues, firstly, that
      individuals may have a legitimate interest in not knowing their genetic make up
      to avoid serious psychological consequences; secondly, that this interest, far
      from being contrary to autonomy, may constitute an enhancement of autonomy;
      thirdly, that the right not to know cannot be presumed, but must be "activated"
      by the individual's explicit choice, and fourthly, that this is not an absolute
      right, in the sense that it may be restricted when disclosure to the patient is
      necessary in order to avoid a risk of serious harm to third persons.

PMID- 15467073
TI  - Euthanasia: above ground, below ground.
AB  - The key to the euthanasia debate lies in how best to regulate what doctors do.
      Opponents of euthanasia frequently warn of the possible negative consequences of
      legalising physician assisted suicide and active euthanasia (PAS/AE) while
      ignoring the covert practice of PAS/AE by doctors and other health professionals.
      Against the background of survey studies suggesting that anything from 4% to 10%
      of doctors have intentionally assisted a patient to die, and interview evidence
      of the unregulated, idiosyncratic nature of underground PAS/AE, this paper
      assesses three alternatives to the current policy of prohibition. It argues that
      although legalisation may never succeed in making euthanasia perfectly safe,
      legalising PAS/AE may nevertheless be safer, and therefore a preferable policy
      alternative, to prohibition. At a minimum, debate about harm minimisation and the
      regulation of euthanasia needs to take account of PAS/AE wherever it is
      practised, both above and below ground.

PMID- 15467074
TI  - The unfeasibility of requests for euthanasia in advance directives.
AB  - In April 2002 a new law regarding euthanasia came into effect in The Netherlands.
      This law holds that euthanasia remains a criminal offence unless it is (1)
      performed by a physician who (2) acts according to six specified rules of due
      care and (3) reports the case to a review committee. The six rules of due care
      are similar to those of the previous regulation and are largely based on
      jurisprudence. Completely new, however, is the article concerning a competent
      patient who has written an advance directive requesting euthanasia under certain
      circumstances. The law stipulates that a physician may act according to that
      written request, as long as he or she fulfils all other rules of due care. The
      author defends the view that these requests are neither feasible nor ethically
      justifiable, and presents both moral and practical arguments for this, claiming
      that for consistency reasons one cannot act on the basis of a written statement
      and fulfil the other rules of due care at the same time. The author also examines
      a difficult case of a demented, severely depressed woman who had written a living
      will requesting euthanasia before she became demented.

PMID- 15467077
TI  - Relatives' knowledge of decision making in intensive care.
AB  - BACKGROUND/AIM: The law on consent has changed in Scotland with the introduction
      of the Adults with Incapacity (Scotland) Act 2000. This Act introduces the
      concept of proxy consent in Scotland. Many patients in intensive care are unable
      to participate in the decision making process because of their illness and its
      treatment. It is normal practice to provide relatives with information on the
      patient's condition, treatment, and prognosis as a substitute for discussion
      directly with the patient. The relatives of intensive care patients appeared to
      believe that they already had the right to consent on behalf of an incapacitated
      adult. The authors' aim was to assess the level of knowledge among relatives of
      intensive care patients of both the old and new law using a structured
      questionnaire. METHODS: The next of kin of 100 consecutive patients completed a
      structured questionnaire. Each participant had the questions read to them and
      their answers recorded. Patients were not involved in the study. RESULTS: Few
      (10%) were aware of the changes. Most (88%) thought that they previously could
      give consent on behalf of an incapacitated adult. Only 13% have ever discussed
      the preferences for life sustaining treatment with the patient but 84% felt that
      they could accurately represent the patient's wishes. CONCLUSIONS: There appeared
      to be a lack of public awareness of the impending changes. The effectiveness of
      the Act at improving the care of the mentally incapacitated adult will depend
      largely on how successful it is at encouraging communication and decision making
      in advance of incapacity occurring.

PMID- 15467076
TI  - Pressure and coercion in the care for the addicted: ethical perspectives.
AB  - The use of coercive measures in the care for the addicted has changed over the
      past 20 years. Laws that have adopted the "dangerousness" criterion in order to
      secure patients' rights to non-intervention are increasingly subjected to
      critique as many authors plead for wider dangerousness criteria. One of the most
      salient moral issues at stake is whether addicts who are at risk of causing
      danger to themselves should be involuntarily admitted and/or treated. In this
      article, it is argued that the dilemma between coercion on the one hand and
      abandonment on the other cannot be analysed without differentiated perspectives
      on the key notions that are used in these debates. The ambiguity these notions
      carry within care practice indicates that the conflict between the prevention of
      danger and respect for autonomy is not as sharp as the legal systems seem to
      imply. Some coercive measures need not be interpreted as an infringement of
      autonomy--rather, they should be interpreted as a way to provide good care.

PMID- 15467079
TI  - Returning to the Alder Hey report and its reporting: addressing confusions and
      improving inquiries.
AB  - The Royal Liverpool Children's Inquiry investigated the circumstances leading to
      the removal, retention, and disposal of human tissue, including children's
      organs, at the Royal Liverpool Children's NHS Trust (the Alder Hey Hospital). It
      recommended changes to procedures for obtaining consent for postmortems and
      retaining organs and tissues for research or education. However, the report
      contains five areas of confusion. Firstly, it allowed the cultural and historical
      traditions of horror over the use and misuse of body parts to suffuse the logical
      analysis of past wrongs and future rights. Secondly, it makes an inappropriate
      conflation between seeking redress for past wrongs and shaping future policy.
      Thirdly, the report takes a muddled stance over the value of bodily integrity at
      burial. Fourthly, the report is inconsistent over the justification for future
      organ and tissue collections. Fifthly, the notion of "respect" is used with
      troublesome looseness. The extent to which subsequent policy work has furthered
      the search for greater ethical clarity over these difficult issues is discussed,
      together with reflection on three particular improvements that could be made to
      the process of such an inquiry.

PMID- 15467080
TI  - Are patents for methods of medical treatment contrary to the ordre public and
      morality or "generally inconvenient"?
AB  - "No one has advanced a just and logical reason why reward for service to the
      public should be extended to the inventor of a mechanical toy and denied to the
      genius whose patience, foresight, and effort have given a valuable new
      [discovery] to mankind" (Katopis CJ. Patents v patents: policy implications of
      recent patent legislation. St John's Law Review 1997;71:329). The law around the
      world permits the granting of patents for drugs, medical devices, and cosmetic
      treatment of the human body. At the same time, patentability for a method of
      treatment of the same body is denied in some countries on various public policy
      grounds. Is there any logical justification for this distinction? Are methods of
      medical treatment not as vital to the health or even to the life of a patient as
      drugs or medical devices? Why is a cosmetic result patentable and a curative
      result not?

PMID- 15467082
TI  - Misconceived conceptions.

PMID- 15467083
TI  - Sex and the surgery: students' attitudes and potential behaviour as they pass
      through a modern medical curriculum.
AB  - OBJECTIVE: To examine students' attitudes and potential behaviour to a possible
      intimate relationship with a patient as they pass through a modern medical
      curriculum. DESIGN: A cohort study of students entering Glasgow University's new
      learner centred, integrated medical curriculum in October 1996. METHODS:
      Students' pre year 1 and post year 1, post year 3, and post year 5 responses to
      the "attractive patient" vignette of the Ethics in Health Care Survey instrument
      were examined quantitatively and qualitatively. Analysis of students' multi
      choice answers enabled measurement of the movement towards professional consensus
      opinion. Analysis of written justifications helped determine whether their
      reasoning was consistent with professional consensus and enabled measurement of
      change in knowledge content and recognition of the values inherent in the
      vignette. Themes on students' reasoning behind their decision to enter a
      relationship or not were also identified. RESULTS: No significant movement
      towards consensus was found at any point in the curriculum. There was little
      improvement in students' performance in terms of knowledge content and their
      abilities to recognise the values inherent in the vignette. In deciding to enter
      a relationship with the patient the most frequently used reasoning was that it
      could be justified if the patient changed their doctor. CONCLUSIONS: Teaching on
      the subject of sexual or improper relationships between doctors and patients,
      including relationships with former patients requires to be made explicit. Case
      based teaching would fit in with the ethos of the problem based, integrated
      medical curriculum.

PMID- 15467084
TI  - Helping medical students to find their moral compasses: ethics teaching for
      second and third year undergraduates.
AB  - The paper describes a two week course that has been offered as a special study
      module to intermediate level (second and third year) undergraduate medical
      students at Dundee University Medical School for the past five years. The course
      requires students to research the various aspects of ethical dilemmas that they
      have identified themselves, and to "teach" these issues to their colleagues in a
      short PowerPoint presentation as well as to prepare an extended 3000 word essay
      discussion. The course specifically asks students not to disclose their own
      ethical positions, as these are probably still in formation and the objective is
      to promote critical thinking capacity in ethical and moral issues as a prelude to
      the development of practical skills in dealing with clinical problems. The course
      is easy to resource for the school and has received universally high evaluations
      from the students since its inception.

PMID- 15467085
TI  - Avoiding evasion: medical ethics education and emotion theory.
AB  - Beginning with an exemplary case study, this paper diagnoses and analyses some
      important strategies of evasion and factors of hindrance that are met in the
      teaching of medical ethics to undergraduate medical students. Some of these
      inhibitions are inherent to ethical theories; others are connected with the
      nature of medicine or cultural trends. It is argued that in order to avoid an
      attitude of evasion in medical ethics teaching, a philosophical theory of
      emotions is needed that is able to clarify on a conceptual level the ethical
      importance of emotions. An approach is proposed with the help of the emotion
      theory Martha Nussbaum works out in her book Upheavals of thought. The paper ends
      with some practical recommendations.

PMID- 15467086
TI  - Involvement of nurses in euthanasia: a review of the literature.
AB  - In ethical debates about euthanasia, the focus is often exclusively on the
      involvement of physicians and the involvement of nurses is seldom given much
      attention. Yet nurses occupy a central position in the care of terminal patients,
      where being confronted with a euthanasia request is an ever present possibility.
      To assess the involvement of nurses in euthanasia, this article provides an
      overview of relevant findings from the scientific literature. From this it
      becomes apparent that nurses are involved in various phases of the euthanasia
      process: observing the request for euthanasia, decision making, carrying out of
      euthanasia, and the aftercare for the patient's family members.

PMID- 15467087
TI  - Internists' attitudes towards terminal sedation in end of life care.
AB  - OBJECTIVE: To describe the frequency of support for terminal sedation among
      internists, determine whether support for terminal sedation is accompanied by
      support for physician assisted suicide (PAS), and explore characteristics of
      internists who support terminal sedation but not assisted suicide. DESIGN: A
      statewide, anonymous postal survey. SETTING: Connecticut, USA. PARTICIPANTS: 677
      Connecticut members of the American College of Physicians. MEASUREMENTS:
      Attitudes toward terminal sedation and assisted suicide; experience providing
      primary care to terminally ill patients; demographic and religious
      characteristics. RESULTS: 78% of respondents believed that if a terminally ill
      patient has intractable pain despite aggressive analgesia, it is ethically
      appropriate to provide terminal sedation (diminish consciousness to halt the
      experience of pain). Of those who favoured terminal sedation, 38% also agreed
      that PAS is ethically appropriate in some circumstances. Along a three point
      spectrum of aggressiveness in end of life care, the plurality of respondents
      (47%) were in the middle, agreeing with terminal sedation but not with PAS.
      Compared with respondents who were less aggressive or more aggressive, physicians
      in this middle group were more likely to report having more experience providing
      primary care to terminally ill patients (p = 0.02) and attending religious
      services more frequently (p<0.001). CONCLUSIONS: Support for terminal sedation
      was widespread in this population of physicians, and most who agreed with
      terminal sedation did not support PAS. Most internists who support aggressive
      palliation appear likely to draw an ethical line between terminal sedation and
      assisted suicide.

PMID- 15467089
TI  - WHO membership: the plight of Taiwan.

PMID- 15467090
TI  - Aiming towards "moral equilibrium": health care professionals' views on working
      within the morally contested field of antenatal screening.
AB  - OBJECTIVE: To explore the ways in which health care practitioners working within
      the morally contested area of prenatal screening balance their professional and
      private moral values. DESIGN: Qualitative study incorporating semistructured
      interviews with health practitioners followed by multidisciplinary discussion
      groups led by a health care ethicist. SETTING: Inner city teaching hospital and
      district general hospital situated in South East England. PARTICIPANTS: Seventy
      practitioners whose work relates directly or indirectly to perinatal care.
      RESULTS: Practitioners managed the interface between their professional and
      private moral values in a variety of ways. Two key categories emerged:
      "tolerators", and "facilitators". The majority of practitioners fell into the
      "facilitator" category. Many "facilitators" felt comfortable with the prevailing
      ethos within their unit, and appeared unlikely to feel challenged unless the
      ethos was radically challenged. For others, the separation of personal and
      professional moral values was a daily struggle. In the "tolerator" group, some
      practitioners sought to influence the service offered directly, whereas others
      placed limits on how they themselves would contribute to practices they
      considered immoral. CONCLUSIONS: The "official" commitment to non-directiveness
      does not encourage open debate between professionals working in morally contested
      fields. It is important that practical means can be found to support
      practitioners and encourage debate. Otherwise, it is argued, these fields may
      come to be staffed by people with homogeneous moral views. This lack of diversity
      could lead to a lack of critical analysis and debate among staff about the ethos
      and standards of care within their unit.

PMID- 15467091
TI  - There is a difference between selecting a deaf embryo and deafening a hearing
      child.
AB  - If genetic diagnosis and preimplantation selection could be employed to produce
      deaf children, would it be acceptable for deaf parents to do so? Some say no,
      because there is no moral difference between selecting a deaf embryo and
      deafening a hearing child, and because it would be wrong to deafen infants. It is
      argued in this paper, however, that this view is untenable. There are differences
      between the two activities, and it is perfectly possible to condone genetic
      selection for deafness while condemning attempts to deafen infants at birth.

PMID- 15467092
TI  - The not-so-sweet science: the role of the medical profession in boxing.

PMID- 15467093
TI  - The search for meaningful comparisons in boxing and medical ethics.

PMID- 15467094
TI  - Compulsory brain scans and genetic tests for boxers--or should boxing be banned?

PMID- 15467095
TI  - Attraction or repulsion: a matter of individual taste?
AB  - Cell migration along the correct paths is critical to normal organogenesis and
      tissue repair, and goes awry in tumor dissemination. Understanding the molecular
      cues that control such migration would provide opportunities to control these
      events. Recent findings in Drosophila highlight the role of the epidermal growth
      factor receptor (EGFR) in chemotaxis and pathfinding during development. These
      studies, and others performed in vertebrates, support a central role for EGFR
      mediated chemotaxis. However, the signal or signals that then enable cells to
      further migrate independently of this chemotactic effect are not known. Three
      possible scenarios are discussed: that EGFR signaling sensitizes cells to new
      cues, that EGFR signaling is altered so that the cell responds predominantly to
      other motility signals that are now "unblinded," and that EGFR signaling still
      provides the motile signal but in a chemokinetic manner with matrix components
      providing the directionality. There are precedents for all three scenarios, but
      which one proves true will define the window of opportunity for regulating cell
      migration.

PMID- 15467096
TI  - The VGL-chanome: a protein superfamily specialized for electrical signaling and
      ionic homeostasis.
AB  - Complex multicellular organisms require rapid and accurate transmission of
      information among cells and tissues and tight coordination of distant functions.
      Electrical signals and resulting intracellular calcium transients, in
      vertebrates, control contraction of muscle, secretion of hormones, sensation of
      the environment, processing of information in the brain, and output from the
      brain to peripheral tissues. In nonexcitable cells, calcium transients signal
      many key cellular events, including secretion, gene expression, and cell
      division. In epithelial cells, huge ion fluxes are conducted across tissue
      boundaries. All of these physiological processes are mediated in part by members
      of the voltage-gated ion channel protein superfamily. This protein superfamily of
      143 members is one of the largest groups of signal transduction proteins, ranking
      third after the G protein-coupled receptors and the protein kinases in number.
      Each member of this superfamily contains a similar pore structure, usually
      covalently attached to regulatory domains that respond to changes in membrane
      voltage, intracellular signaling molecules, or both. Eight families are included
      in this protein superfamily-voltage-gated sodium, calcium, and potassium
      channels; calcium-activated potassium channels; cyclic nucleotide-modulated ion
      channels; transient receptor potential (TRP) channels; inwardly rectifying
      potassium channels; and two-pore potassium channels. This article identifies all
      of the members of this protein superfamily in the human genome, reviews the
      molecular and evolutionary relations among these ion channels, and describes
      their functional roles in cell physiology.

PMID- 15467097
TI  - Effects of antioxidant therapy in women exposed to eccentric exercise.
AB  - The purpose of this study was to determine the effects of antioxidant therapy on
      indirect markers of muscle damage following eccentric exercise (EE). Eighteen
      women were randomized to an antioxidant supplement or a placebo before a bout of
      EE. Plasma creatine kinase (CK) activity, muscle soreness (MS), maximal isometric
      force (MIF), and range of motion (ROM) were assessed before and through 14 d
      postexercise. Eccentric exercise resulted in an increase in CK activity and MS,
      and a drop in MIF and ROM during the days following EE, which returned to
      baseline values 14 d after EE in both groups. Antioxidants attenuated the CK
      activity and MS response to the EE, while little difference was noted between
      groups in MIF or ROM. These findings suggest that antioxidant supplementation was
      helpful in reducing the elevations in plasma CK activity and MS, with little
      impact on MIF and ROM loss.

PMID- 15467098
TI  - Nutrient intakes and dietary behaviors of male and female collegiate athletes.
AB  - The purpose of this study was to assess the dietary intakes and behaviors of male
      and female collegiate athletes. Athletes (n =345) at a NCAA Division I university
      completed an anonymous questionnaire. T-tests, chi(2) statistic, and ANOVA were
      used to assess gender and sport differences. Multiple linear regression was used
      to assess gender differences in nutrient intakes, controlling for energy intake
      and to examine the relationships between desired weight change, dietary
      behaviors, and nutrient intakes. Only 15 % and 26 % of athletes had adequate
      intakes of carbohydrate and protein, respectively, based on recommendations for
      athletes. Males were more likely to exceed the Dietary Guidelines for fat,
      saturated fat, cholesterol, and sodium than females. Sixty-two percent of female
      athletes wanted to lose at least 5 lbs compared to 23 % of males. The desire to
      lose weight was associated with decreased energy and macronutrient consumption,
      but not with inadequate micronutrient intakes.

PMID- 15467099
TI  - Eating attitudes, exercise identity, and body alienation in competitive
      ultramarathoners.
AB  - This study examined the relationships among eating attitudes, exercise identity,
      and body alienation in ultramarathoners. Eighty-seven competitive
      ultramarathoners (73 males, 14 females) completed the Eating Attitudes Test-26,
      Exercise Identity Scale, and Body Alienation Scale as part of their pre-race
      registration. Correlation coefficients revealed that eating attitudes were
      positively related to exercise identity (R = 0.31) and injury tolerance (R =
      0.43), and that exercise identity was positively related to injury tolerance (R =
      0.33). MANOVA further indicated that subjects with high exercise identity
      reported more eating disorder behaviors [F(2, 80) = 7.73, P <0.001] and higher
      injury tolerance [F(2, 80) = 3.69, P <0.05] than persons with low exercise
      identity. Female ultramarathoners scoring high on exercise identity were more
      likely to report aberrant eating behaviors [F(2, 80) = 3.39, P <0.05] and higher
      training intensity levels [F(2, 80) = 3.91, P <0.02] than were average males and
      the low- or moderate-exercise identifying females.

PMID- 15467100
TI  - Rehydration with a caffeinated beverage during the nonexercise periods of 3
      consecutive days of 2-a-day practices.
AB  - The purpose of this study was to assess the influence of rehydration with a
      caffeinated beverage during nonexercise periods on hydration status throughout
      consecutive practices in the heat. Ten (7 women, 3 men) partially heat-
      acclimated athletes (age 24 +/-1y, body fat 19.2 +/- 2 %, weight 68.4 +/- 4.0 kg,
      height 170 +/- 3 cm) completed 3 successive days of 2-a-day practices (2
      h/practice, 4 h/d) in mild heat (WBGT = 23 C). The 2 trials (double-blind,
      random, cross-over design) included; 1) caffeine (CAF) rehydrated with Coca-Cola
      and 2) caffeine-free (CF) rehydrated with Caffeine-Free Coca-Cola. Urine and
      psychological measures were determined before and after each 2-h practice. A
      significant difference was found for urine color for the post-AM time point, F =
      5.526, P = 0.031. No differences were found among other variables (P > 0.05). In
      summary, there is little evidence to suggest that the use of beverages containing
      caffeine during nonexercise might hinder hydration status.

PMID- 15467102
TI  - The effects of creatine supplementation on cardiovascular, metabolic, and
      thermoregulatory responses during exercise in the heat in endurance-trained
      humans.
AB  - The effects of creatine (Cr) supplementation on cardiovascular, metabolic, and
      thermoregulatory responses, and on the capacity of trained humans to perform
      prolonged exercise in the heat was examined. Endurance-trained males (n = 21)
      performed 2 constant-load exercise tests to exhaustion at 63 +/- 5 % VO(2max) in
      the heat (ambient temperature: 30.3 +/- 0.5 C) before and after 7 d of Cr (20 g x
      d (-1 ) Cr + 140 g x d (-1 ) glucose polymer) or placebo. Cr increased
      intracellular water and reduced thermoregulatory and cardiovascular responses
      (e.g., heart rate, rectal temperature, sweat rate) but did not significantly
      increase time to exhaustion (47.0 +/-4.7 min vs. 49.7 +/- 7.5 min, P =0.095).
      Time to exhaustion was increased significantly in subjects whose estimated
      intramuscular Cr levels were substantially increased ("responders" : 47.3 +/- 4.9
      min vs. 51.7 +/- 7.4 min, P = 0.031). Cr-induced hyperhydration can result in a
      more efficient thermoregulatory response during prolonged exercise in the heat.

PMID- 15467101
TI  - Resistive training and chromium picolinate: effects on inositols and liver and
      kidney functions in older adults.
AB  - This study assessed the effects of resistive training (RT) with or without
      chromium picolinate (Cr-pic) supplementation on the 24-h urinary excretions of
      myo-inositol, D-chiro-inositol, and pinitol, as well as clinical indices of
      kidney and liver functions. Thirty-two nondiabetic subjects, age 62 +/- 4 y,
      performed RT twice weekly for 12 wk and consumed either 924 ug Cr/d as Cr-pic (n
      = 17) or a placebo (n = 15). Whole-body strength increased in all subjects by 20
      % and urinary chromium excretion increased 47-fold in the Cr-pic group. Urinary
      myo-inositol, D-chiro-inositol, and pinitol were not changed with RT or
      influenced by Cr-pic. Serum indices of kidney and liver functions were within
      clinically normal ranges at baseline and the end of the study. These results
      suggest that RT did not influence the urinary excretions of inositols. High dose
      Cr-pic did not influence the urinary excretion of inositols and the selected
      indices of kidney and liver functions in conjunction with RT.

PMID- 15467103
TI  - Effects of an alleged myostatin-binding supplement and heavy resistance training
      on serum myostatin, muscle strength and mass, and body composition.
AB  - This study examined 12 wk of resistance training and cystoseira canariensis
      supplementation on serum levels of myostatin and follistatin-like related gene
      (FLRG) and muscle strength and body composition. Twenty-two untrained males were
      randomly assigned to a placebo (PLC) or myostatin binder (MYO) group in a double
      blind fashion. Blood was obtained before and after 6 and 12 wk of training. PLC
      and MYO trained thrice weekly using 3 sets of 6 to 8 repetitions at 85 % to 90 %
      1 repetition maximum. MYO ingested 1200 mg/d of cystoseira canariensis. Data were
      analyzed with 2-way ANOVA. After training, total body mass, fat-free mass, muscle
      strength, thigh volume/mass, and serum myostatin and FLRG increased for both
      groups (P < 0.05); however, there were no differences between groups (P > 0.05).
      Twelve wk of heavy resistance training and 1200 mg/d of cystoseira canariensis
      supplementation appears ineffective at inhibiting serum myostatin and increasing
      muscle strength and mass or decreasing fat mass.

PMID- 15467104
TI  - Doping-control urinalysis of a ginseng extract, Cold-FX, in athletes.
AB  - Nutraceuticals may induce doping infractions through contamination of the product
      itself or their ingestion might be metabolized within the body to create a
      positive doping control test. We tested this possibility using a commercially
      available, proprietary ginseng root extract (Cold-FX, CV Technologies Inc.,
      Edmonton, AB). After athletes ingested Cold-FX for 28 d at 400 mg/d, urine
      samples were collected and processed under strict IOC doping control guidelines
      and then analyzed for a full screen of IOC banned/restricted substances by an IOC
      approved laboratory. There were no positive tests for any banned substances in
      any of the subjects. Our study demonstrates that ingestion of Cold-FX for 28 d at
      400 mg/d does not represent a doping concern for athletes. Carefully controlled
      clinical studies like this one are necessary to provide the athlete, the
      nutraceutical industry and IOC regulatory bodies with information to avoid
      inadvertent exposure to banned/restricted or potentially unhealthy substances.

PMID- 15467105
TI  - Prevalent use of dietary supplements among people who exercise at a commercial
      gym.
AB  - Supplement use was surveyed in a convenience sample of persons who exercised
      regularly at a Long Island, NY gym. Participants, age at least 18 y, completed
      anonymous questionnaires. A majority (84.7 %) took supplements. Many consumed
      multivitamin/minerals (MVM; 45 %), protein shakes/bars (PRO; 42.3 %), vitamin C
      (34.7 %), and vitamin E (VE; 23.4 %) at least 5 times per wk. Other dietary
      supplements were used less frequently or by fewer participants. Ephedra was
      consumed by 28 % at least once per wk. Choices and reasons for dietary supplement
      use varied with age of the participant. More of the oldest consumed MVM or VE,
      while those 45 y or younger chose PRO. Those younger than 30 consumed creatine
      more frequently. The oldest participants took supplements to prevent future
      illness, while others took supplements to build muscle. The reason for committing
      to an exercise program influenced supplement use. Bodybuilders more frequently
      consumed PRO, creatine, and ephedra compared to those exercising for health
      reasons.

PMID- 15467106
TI  - Contamination of supplements: an interview with professor Ron Maughan by Louise
      M. Burke.
AB  - This issue of IJSNEM features two articles related to supplement use by athletes.
      In one (Morrison et al. 2004), people who undertake regular exercise in a gym
      were found to report the use of a wide variety of supplements. The other paper
      (Goel et al. 2004) dealt with one of the issues that a sub-group of athletes need
      to consider before deciding to take supplements - the risk of a positive drug
      test if the product contains substances banned by the anti-doping codes under
      which their sport is conducted. This issue received much publicity earlier in the
      year when top tennis player Greg Rusedski tested positive for the steroid
      nandrolone as the result of inadvertent intake via a contaminated supplement. In
      this article, Professor Ron Maughan, Chair of Sports Nutrition at Loughborough
      University in the United Kingdom, advisor to the British Olympic team, and co
      editor of IJSNEM, provides his insight on this important topic.

PMID- 15467107
TI  - Effects of trace elements on the telomere lengths of hepatocytes L-02 and
      hepatoma cells SMMC-7721.
AB  - The effects of selenium, zinc, iron, chromium, and lead on telomere lengths of
      human cells have not been investigated. This article adopted flow cytometry and
      fluorescence in situ hybridization to investigate the impact of different
      elements on cellular apoptosis and telomere lengths of human hepatocytes L-02 and
      hepatoma cells SMMC-7721. Results showed that these trace elements under the
      following dosages did not have remarkable effect on cellular apoptosis. However,
      sodium selenite at doses of 0.5 and 2.5 micromol/L significantly extended the
      telomere length of hepatocytes L-02; 0.5 micromol/L lead acetate remarkably
      shortened the telomere length of L-02 cells; 80 micromol/L zinc sulfate, 20
      micromol/L ferric chloride, and 200 micromol/L chromic chloride only had slight
      impact on the telomere length, respectively. Regarding hepatoma cells SMMC-7721,
      sodium seleite at 0.5 and 2.5 micromol/L had little impact on the telomere
      length; 80 micromol/L zinc sulfate significantly accelerated the loss of telomere
      length, whereas 20 micromol/L ferric chloride, 200 micromol/L chromic chloride,
      and 0.5 micromol/L lead acetate remarkably extended the telomere lengths,
      respectively. The results revealed differential effects of each trace element on
      the life-span of human hepatocytes and hepatoma cell lines, which suggested
      further research on somatic hepatocytes and hepatoma in vivo.

PMID- 15467108
TI  - Effect of lead ions on rat erythrocyte purine content.
AB  - The influence of short-term exposure to lead on the energetic status of
      erythrocytes in rats is reported in this study. The male Wistar rats selected for
      this study drank water containing 1% lead(II) acetate and/or intraperitoneal
      injections of 1 or 2 mg/kg body wt every 4 d starting on the eighth of the
      experiment, over a period of 1 mo. The whole-blood lead concentration measured
      after 4 wk was 1.51-35.31 microg/dL. The concentrations of adenosine, adenosine
      triphosphates, diphosphates, and monophosphates (ATP, ADP, and AMP), guanine
      triphosphates, diphosphates and monophosphates (GTP, GDP, and GMP), guanosine
      (Guo), inosine (Ino), inosine monophosphate (IMP), hypoxantine (Hyp), and
      nicotinamide dinucleotide and its phosphate (NAD(+) and NADP(+)) were determined
      by high-performance liquid chromatography (HPLC). The mean concentrations of ATP,
      GTP, NAD(+), and NADP(+) and those of adenylate (AEC) and guanylate (GEC) were
      significantly reduced in erythrocytes from the animals exposed to lead when
      compared to untreated controls. These results suggest that a lead ion disrupts
      the erythrocyte energy pathways. The decreases of NAD(+) and ATP could be used as
      an indicator of the extent of exposure to low levels of lead.

PMID- 15467109
TI  - Calcium and strontium thiosulfate, CaS2O3.6H2O and SrS2O3.5H2O.

PMID- 15467110
TI  - Transition metal complexes with pyrazole-based ligands. XIX. Diaquabis(3,5
      dimethyl-1H-pyrazole-1-carboxamidine-kappa2N,N')metal(II) dinitrate, with metal =
      Co and Ni.

PMID- 15467111
TI  - catena-Poly[[(nitrato-kappa2O,O')silver(I)]-mu-2,2'-[1,4
      phenylenebis(methylenethio)]bis(5-methyl-1,3,4-thiadiazole)-kappa2N3:N3'].

PMID- 15467112
TI  - Dicarbonyl(tropolonato)rhodium(I), a redetermination.

PMID- 15467113
TI  - 1,4-Dimethylpyridinium hexakis(dimethylformamide-kappaO)calcium(II)
      dodecamolybdophosphate.

PMID- 15467114
TI  - Tetrakis(2,2'-bipyridine-kappa2N,N')tetrakis(mu-salicylato-kappa3O,O':O'')-quadro
      tetrazinc(II) decahydrate.

PMID- 15467115
TI  - Dibromotetra-mu3-methoxo-di-mu2-methoxo-hexakis(tetrahydrofuran
      d8)tetramagnesium.

PMID- 15467116
TI  - Comparative study of two chemically isostructural polymers:
      [Cu2(VO2)(HPO4)2(NO3)(bpy)2].2H2O/H3PO4 (bpy is 2,2'-bipyridine).

PMID- 15467117
TI  - (2,2'-Bipyridyl-kappa2N,N')bis(salicylato-kappa2O,O')zinc(II).

PMID- 15467118
TI  - The one-dimensional structure of Cu(dmen)2Pd(CN)4 (dmen is N,N
      dimethylethylenediamine).

PMID- 15467119
TI  - A new binding mode for thiosulfate in six-coordinate poly[[(1,10-phenanthroline
      kappa2N,N')cadmium(II)]-mu-thiosulfato].

PMID- 15467120
TI  - Diaqua(sulfato-kappaO)[2,4,6-tris(2-pyridyl)-1,3,5-triazine
      kappa3N1,N2,N6]zinc(II) dihydrate.

PMID- 15467121
TI  - Poly[manganese(II)-mu2-benzidine-kappa2N:N'-mu3-biphenyl-2,2'-dicarboxylato
      kappa4O:O',O'':O'''].

PMID- 15467122
TI  - Poly[diaqua-mu4-oxalato-di-mu6-phosphato-tetrazinc].

PMID- 15467123
TI  - Bis[1,3-bis(trimethylsilyl)allyl]cobalt(II), a stable electron-deficient allyl
      complex.

PMID- 15467124
TI  - Poly[[copper(II)-di-mu-5-aminoisophthalato(1-)-kappa4N:O] monohydrate].

PMID- 15467125
TI  - [Cu(phen)2(mu-IDA)Cu(phen)](ClO4)2.-CH3OH: tridentate and monodentate binding to
      two copper(II) species by a bridging ligand.

PMID- 15467126
TI  - catena-Poly[[silver(I)-mu-ethane-1,2-diamine-kappa2N:N']
      trifluoromethanesulfonate].

PMID- 15467127
TI  - Bis(mu-2-aminopyridine)bis[(trifluoroacetato)silver(I)].

PMID- 15467128
TI  - catena-Poly[[bis(quinoxaline-kappaN)cobalt(II)]-di-mu-dicyanamido-kappa2N1:N5)
      and catena-poly[[bis(quinoxaline-kappaN)copper(II)]-di-mu-dicyanamido
      kappa2N1:N5].

PMID- 15467129
TI  - Aquadichloro(di-2-pyridyldiazene)copper(II) monohydrate.

PMID- 15467130
TI  - Bis(1,10-phenanthroline-kappa2N,N')(squarato-kappaO)copper(II) trihydrate.

PMID- 15467131
TI  - Polysulfonylamines. CLXXI. [Di(methanesulfonyl)amido-kappaN]bis(2-picoline
      kappaN)copper(I).

PMID- 15467132
TI  - (R,R)-Tricarbonyl[eta6-1-(diphenylphosphino)-2-[1
      (diphenylphosphino)ethyl]benzene] chromium(0), (R,R)-tricarbonyl-1kappa3C
      [mu1(eta6):2kappa2P,P'-1-(diphenylphosphino)-2-[1
      (diphenylphosphino)ethyl]benzene][2(eta4)-norbornadiene]chromium(0)rhodium(I)
      tetrafluoroborate methanol 0.75-solvate and (R,R)-tricarbonyl-1kappa3C-[mu
      1(eta6):2kappa2P,P'-1-(diphenylphosphino)-2-[1
      (diphenylphosphino)ethyl]benzene][2(eta4)-(Z,Z)-cycloocta-1,5
      diene]chromium(0)rhodium(I) tetrafluoroborate methanol 1.5-solvate.

PMID- 15467133
TI  - A two-dimensional manganese(II) coordination polymer: poly[[diaquamanganese(II)]
      mu-4,4-bipyridine-kappa(2)N:N'-mu-(p-phenylenedioxydiacetato)-kappa2O:O'].

PMID- 15467134
TI  - Poly[[diaquacobalt(II)]-di-mu-4-cyanobenzoato-kappa4O:O'].

PMID- 15467135
TI  - Di-mu-hydroxo-bis[aqua(1,10-phen-anthroline-kappa2N,N')copper(II)] trans-bis(2
      ([(E)-5-formyl-2-oxido-kappaO-benzylidene]amino-kappaN)ethanesulfonato(2
      ))copper(II) hexahydrate.
AB  - The title compound,
      [Cu(2)(OH)(2)(C(12)H(8)N(2))(2)(H(2)O)(2)][Cu(C(10)H(9)NO(5)S)(2)].6H(2)O, is
      comprised of a copper-centred complex cation and a copper-centred complex anion;
      the cation lies about an inversion centre and in the anion the Cu atom lies on an
      inversion centre. In the doubly charged bridged dicopper cation, each Cu centre
      has distorted square-pyramidal geometry. In the square-planar dianion, two
      sulfonate ligands are trans coordinated to the Cu atom via a deprotonated
      hydroxyl O atom and an imine N atom, forming two six-membered chelate rings. The
      structure is stabilized by an extensive hydrogen-bond system and aromatic-ring
      stacking interactions.

PMID- 15467136
TI  - A novel one-dimensional zigzag coordination polymer of copper(II) with
      dimethylglyoxime.

PMID- 15467137
TI  - 3,3-Bis(2-methoxyphenyl)-3H-benzo[f]chromene.

PMID- 15467138
TI  - Methyl 4-(2-chloro-5-nitrophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8
      hexahydroquinoline-3-carboxylate.

PMID- 15467139
TI  - Hydantoin and hydrogen-bonding patterns in hydantoin derivatives.

PMID- 15467140
TI  - 2-Pyridone-tartronic acid (1/1), 3-hydroxypyridinium hydrogen tartronate and 4
      hydroxypyridinium hydrogen tartronate.

PMID- 15467141
TI  - The E and Z isomers of 3-(benzoxazol-2-yl)prop-2-enoic acid.

PMID- 15467142
TI  - (+)-Camphoracetic acid: catemeric hydrogen bonding in a gamma-keto acid.

PMID- 15467143
TI  - 1H-Imidazol-1-yl 1,2,3,4-tetrahydroisoquinolin-2-yl ketone.

PMID- 15467144
TI  - Hydrogen-bonded chains in 5-methyl-2-trifluoromethyl-1,2,4-triazolo[1,5
      a]pyrimidin-7(4H)-one and hydrogen-bonded chains of rings in 5-amino-3
      trifluoromethyl-1H-1,2,4-triazole-5-methyl-2-trifluoromethyl-1,2,4-triazolo[1,5
      a]pyrimidin-7(4H)-one (1/1), the co-crystal of a reaction product and one of its
      precursors.

PMID- 15467145
TI  - 6-(3,4-Difluorobenzoyl)-3-[2-(4-pyridyl)ethyl]-1,3-benzothiazol-2(3H)-one.

PMID- 15467146
TI  - Two N,N-dimethylbiguanidium salts displaying double hydrogen bonds to the counter
      ions.

PMID- 15467147
TI  - Polarized molecular-electronic structures and supramolecular aggregation in 1-(6
      amino-1,3-benzodioxol-5-yl)-3-arylprop-2-en-1-ones.

PMID- 15467148
TI  - 1-Chloro-1,3,3,5,5-pentaphenoxycyclotriphosphazene: a precursor of functionalized
      cyclophosphazene derivatives.

PMID- 15467149
TI  - The twinned crystal structure of rac-(R,R)-N,N'-oxalyldivalinol.

PMID- 15467150
TI  - 2-[6-(3-Chlorophenyl)-2,4-dioxoperhydropyrimidin-3-yl]ethyl morpholine-4
      carbodithioate.

PMID- 15467152
TI  - (+/-)-(4-Oxo-4H-chromen-2-yl)(phenyl)methyl acetate.

PMID- 15467151
TI  - Hydrogen-bonding patterns in cis-4-ammoniocyclohexanecarboxylate hemihydrate.

PMID- 15467154
TI  - 4-Nitroanilinium nitrate.

PMID- 15467153
TI  - The 1:1 adduct of 5-methylbenzene-1,3-diol (orcin) and 1,4
      diazabicyclo[2.2.2]octane.

PMID- 15467155
TI  - L-Seryl-L-phenylalanine.

PMID- 15467156
TI  - Cancer Diagnostics Integrated With Therapeutics: A Comprehensive Approach to
      Managing the Disease.

PMID- 15467157
TI  - Effect of Synthetic Truncated Apolipoprotein C-I Peptide on Plasma Lipoprotein
      Cholesterol in Nonhuman Primates.
AB  - The present studies were conducted to determine whether a synthetic truncated
      apoC-I peptide that inhibits CETP activity in baboons would raise plasma HDL
      cholesterol levels in nonhuman primates with low HDL levels. We used 2 cynomolgus
      monkeys and 3 baboons fed a cholesterol- and fat-enriched diet. In cynomolgus
      monkeys, we injected synthetic truncated apoC-I inhibitor peptide at a dose of 20
      mg/kg and, in baboons, at doses of 10, 15, and 20 mg/kg at weekly intervals.
      Blood samples were collected 3 times a week and VLDL $+$ LDL and HDL cholesterol
      concentrations were measured. In cynomolgus monkeys, administration of the
      inhibitor peptide caused a rapid decrease in VLDL $+$ LDL cholesterol
      concentrations (30%-60%) and an increase in HDL cholesterol concentrations (10%
      20%). VLDL $+$ LDL cholesterol concentrations returned to baseline levels in
      approximately 15 days. In baboons, administration of the synthetic inhibitor
      peptide caused a decrease in VLDL $+$ LDL cholesterol (20%-60%) and an increase
      in HDL cholesterol (10%-20%). VLDL $+$ LDL cholesterol returned to baseline
      levels by day 21, whereas HDL cholesterol concentrations remained elevated for up
      to 26 days. ApoA-I concentrations increased, whereas apoE and triglyceride
      concentrations decreased. Subcutaneous and intravenous administrations of the
      inhibitor peptide had similar effects on LDL and HDL cholesterol concentrations.
      There was no change in body weight, food consumption, or plasma IgG levels of any
      baboon during the study. These studies suggest that the truncated apoC-I peptide
      can be used to raise HDL in humans.

PMID- 15467158
TI  - Retrotransposition-Competent Human LINE-1 Induces Apoptosis in Cancer Cells With
      Intact p53.
AB  - Retrotransposition of human LINE-1 (L1) element, a major representative non-LTR
      retrotransposon in the human genome, is known to be a source of insertional
      mutagenesis. However, nothing is known about effects of L1 retrotransposition on
      cell growth and differentiation. To investigate the potential for such biological
      effects and the impact that human L1 retrotransposition has upon cancer cell
      growth, we examined a panel of human L1 transformed cell lines following a
      complete retrotransposition process. The results demonstrated that transposition
      of L1 leads to the activation of the p53-mediated apoptotic pathway in human
      cancer cells that possess a wild-type p53. In addition, we found that
      inactivation of p53 in cells, where L1 was undergoing retrotransposition,
      inhibited the induction of apoptosis. This suggests an association between active
      retrotransposition and a competent p53 response in which induction of apoptosis
      is a major outcome. These data are consistent with a model in which human
      retrotransposition is sensed by the cell as a "genetic damaging event" and that
      massive retrotransposition triggers signaling pathways resulting in apoptosis.

PMID- 15467159
TI  - Expression of Mn-Superoxide Dismutase Gene in Nontumorigenic and Tumorigenic
      Human Mammary Epithelial Cells.
AB  - Manganese superoxide dismutase (Mn-SOD), localized at the mitochondrial matrix,
      has the ability to protect cells against oxidative damage. It has been reported
      that low levels of Mn-SOD gene expression cause the development of certain kind
      of tumors. On the other hand, overexpression of Mn-SOD gene may play an important
      role in the development of cancer. In our study, we find that Mn-SOD activity was
      higher in nonaggressive (MCF-7) and aggressive (BT-549 and 11-9-14) breast cancer
      cell lines compared to that of nontumorigenic (MCF-12A and MCF-12F) mammary
      epithelial cell lines. We also observed an increased expression of Mn-SOD gene in
      cancerous cell lines. The elevated level of SOD activity in nonaggressive and
      aggressive breast epithelial cell lines was associated with some changes in
      nucleotide sequence.

PMID- 15467160
TI  - Osteogenic Cells Derived From Embryonic Stem Cells Produced Bone Nodules in Three
      Dimensional Scaffolds.
AB  - An approach for 3D bone tissue generation from embryonic stem (ES) cells was
      investigated. The ES cells were induced to differentiate into osteogenic
      precursors, capable of proliferating and subsequently differentiating into bone
      forming cells. The differentiated cells and the seeded scaffolds were
      characterized using von Kossa and Alizarin Red staining, electron microscopy, and
      RT-PCR analysis. The results demonstrated that ES-derived bone-forming cells
      attached to and colonized the biocompatible and biodegradable scaffolds.
      Furthermore, these cells produced bone nodules when grown for 3-4 weeks in
      mineralization medium containing ascorbic acid and beta-glycerophosphate both in
      tissue culture plates and in scaffolds. The differentiated cells also expressed
      osteospecific markers when grown both in the culture plates and in 3D scaffolds.
      Osteogenic cells expressed alkaline phosphatase, osteocalcin, and osteopontin,
      but not an ES cell-specific marker, oct-4. These findings suggest that ES cell
      can be used for in vitro tissue engineering and cultivation of graftable skeletal
      structures.

PMID- 15467161
TI  - Recovery of the Decorin-Enriched Fraction, Extract (D), From Human Skin: An
      Accelerated Protocol.
AB  - The original extraction procedure of Engel and Catchpole [1] has often been used
      to recover decorin-enriched material from the skin. This material has a strong
      inhibitory effect on fibroblast proliferation, and clearly suppresses it in skin
      except after the first 5-6 days of wounding when new scaffold material is
      required. The aim of our present study has been to find and evaluate the product
      of a faster recovery method, and to check its consistency as a more reliable
      means of regularly obtaining sufficient material for topical application in
      wounds that might become hypertrophic. Modifications of the original Toole and
      Lowther [2] extraction procedure have been carefully evaluated in an attempt to
      cut preparation time without compromising biological activity of the inhibitory
      extract. We have devised a faster recovery procedure without compromising
      biological activity, even if initial recovery has been somewhat reduced. The
      latter problem could be offset by repeated cycles of the final extraction step.
      The main inhibitory activity is shown to be within the decorin-enriched "extract
      D," as the core protein and DSPG II. Adjustment of the extract towards neutrality
      after dialysis against water keeps most of the extracted protein in solution and
      yielded a decorin-enriched preparation that had a specific activity equivalent to
      that of the old method. It also yielded a fraction that was readily lyophilised
      to give a small amount of material that could be stored indefinitely without loss
      of activity and readily redissolved in aqueous solution. A reliable and
      relatively quick method is presented for the production, from human skin, of a
      decorin-enriched preparation that has strong fibroblast inhibitory action. The
      value of the procedure is that it is inexpensive and can produce the quantities
      that might be used topically in reducing hypertrophic scarring of wounds.

PMID- 15467162
TI  - Production of Prednisolone by Pseudomonas oleovorans Cells Incorporated Into
      PVP/PEO Radiation Crosslinked Hydrogels.
AB  - In order to rise the yield of prednisolone from hydrocortisone, the Pseudomonas
      oleovorans cells were entrapped into radiation crosslinked poly (vinyl
      pyrrolidone)/poly(ethylene oxide) (PVP/PEO) hydrogel of different gel contents.
      The factors affecting the gel content and swelling behavior of the polymeric gel,
      such as polymer composition, polymer blend concentration, and irradiation doses,
      were investigated. The formation of gels having a good strength with the ability
      to retain a desirable amount of water in their three-dimensional network can be
      achieved by using PVP/PEO copolymer of composition $(90:10)$ and concentration of
      15% prepared at 20 kGy irradiation dose. At these conditions the prepared
      hydrogel is considered the most favorable one that gave the highest
      hydrocortisone bioconversion and prednisolone yield, 81% and 62.8%, respectively.
      The improvement of prednisolone yield was also achieved by increasing substrate
      concentration. Maximum hydrocortisone bioconversion (86.44) was obtained at 18
      hours by using substrate concentration of 30 mg. Reusability of immobilized
      Pseudomonas oleovorans entrapped into PVP/PEO copolymer hydrogel was studied. The
      results indicated that the transformation capacity of hydrocortisone to
      prednisolone highly increased by the repeated use of copolymer for 4 times. This
      was accompanied by an increase in prednisolone yield to 89% and the bioconversion
      of hydrocortisone was 98.8%.

PMID- 15467164
TI  - The fascination of the Class II.

PMID- 15467163
TI  - Nitric Oxide as a Unique Bioactive Signaling Messenger in Physiology and
      Pathophysiology.
AB  - Nitric oxide (NO) is an intra- and extracellular messenger that mediates diverse
      signaling pathways in target cells and is known to play an important role in many
      physiological processes including neuronal signaling, immune response,
      inflammatory response, modulation of ion channels, phagocytic defense mechanism,
      penile erection, and cardiovascular homeostasis and its decompensation in
      atherogenesis. Recent studies have also revealed a role for NO as signaling
      molecule in plant, as it activates various defense genes and acts as
      developmental regulator. In plants, NO can also be produced by nitrate reductase.
      NO can operate through posttranslational modification of proteins
      (nitrosylation). NO is also a causative agent in various pathophysiological
      abnormalities. One of the very important systems, the cardiovascular system, is
      affected by NO production, as this bioactive molecule is involved in the
      regulation of cardiovascular motor tone, modulation of myocardial contractivity,
      control of cell proliferation, and inhibition of platelet activation,
      aggregation, and adhesion. The prime source of NO in the cardiovascular system is
      endothelial NO synthase, which is tightly regulated with respect to activity and
      localization. The inhibition of chronic NO synthesis leads to neurogenic and
      arterial hypertensions, which later contribute to development of myocardial
      fibrosis. Overall, the modulation of NO synthesis is associated with
      hypertension. This review briefly describes the physiology of NO, its synthesis,
      catabolism, and targeting, the mechanism of NO action, and the pharmacological
      role of NO with special reference to its essential role in hypertension.

PMID- 15467165
TI  - The C-orthodontic micro-implant.

PMID- 15467166
TI  - Retirement plan survey.

PMID- 15467167
TI  - A new eruption attachment for impacted teeth.

PMID- 15467168
TI  - Treatment of posterior open bite using distraction osteogenesis.

PMID- 15467169
TI  - Intra-arch maxillary molar distalization appliances for Class II correction.

PMID- 15467170
TI  - A bonded transpalatal arch.

PMID- 15467172
TI  - Why is revitalizing clinical research so important, yet so difficult?
AB  - We believe that support for academic clinical research has greatly declined in
      recent decades. Here we discuss our views on why this has happened. We define
      clinical or patient-oriented research as limited to the study of human beings or
      populations of individuals, and argue that its eclipse in favor of basic and
      "translational" research is the result of inappropriate conceptual paradigms or
      "models" for medical advances. We believe that medical history shows that the
      "bench-to-bedside" model is inadequate to explain most recent progress and that
      clinical advances themselves often lead to new basic research. Discussion of
      alternate conceptual frameworks for biomedical research should help lead to
      changes in funding and organizational structures that might finally revitalize
      clinical research.

PMID- 15467173
TI  - Remembering the "golden years" of patient-oriented clinical research: a
      collective conversation.
AB  - The period from the end of World War II to the early 1960s has been characterized
      as the "golden years" of patient-oriented clinical research in the United States,
      a period catalyzed and fostered by advances in biology and medicine, changes in
      the organization and financing of research units, and strong moral and political
      convictions growing out of the war about the importance and possibilities of the
      scientific enterprise. This account of some of the salient themes, phenomena, and
      issues in clinical research during that era draws primarily on the proceedings of
      an oral history conference whose core participants were a number of emeritus
      physician-investigators who had played major roles in shaping patient-oriented
      research. The topics that they and the other conferees discussed included the
      factors that had led the emeritus physician-investigators into clinical research;
      the organizational attributes of the units where they had trained and worked,
      focusing particularly on Boston's Peter Bent Brigham Hospital; the vital role
      played by private and federal funding for research and training; and some of the
      changes in the nature of clinical research, research training, and their
      relationships to the care of the sick in the decades since the golden years.

PMID- 15467174
TI  - Denny-Brown, Boston City Hospital, and the history of American neurology.
AB  - Harvard University's Neurological Unit at Boston City Hospital (BCH) became the
      premier center for neurological training in the United States during the middle
      part of the 20th century. During part of this period (1939-1967), it was directed
      by Derek Denny-Brown, who had been recruited from England by Harvard president
      James Conant. The training program that Denny-Brown initiated at BCH emphasized
      neurology as a medical specialty, independent of psychiatry and neurosurgery.
      This program, which reflected Denny-Brown's British training, was remarkably
      effective and served as a model for rest of the country.

PMID- 15467175
TI  - Children in medical research: balancing protection and access--has the pendulum
      swung too far?
AB  - This paper examines the changes in policies regarding children in research
      between 1966 and 2003. The changes reflect a shift in focus from protection to
      access. The need for protection was brought to light in 1966, with the
      publication of Henry Beecher's "Ethics and Clinical Research," which described 22
      research projects that he considered unethical. Four of these involved child
      subjects. Within a few years, Paul Ramsey and Richard McCormick debated the
      ethical acceptability of enrolling children in any non-therapeutic research. The
      first U.S. policies to address the protection of human subjects were written in
      the 1970s and 1980s, and additional protections (Subpart D) were provided to
      child subjects, who were considered particularly vulnerable. In the 1990s,
      however, several new policies were implemented by the National Institutes of
      Health, the Food and Drug Administration, and Congress, in which the focus had
      shifted from protecting children from research risks to ensuring access. The
      article describes the new policies, examines the motivations for the change, and
      describes some of the effects of these policies. It concludes by suggesting that
      greater attention must be paid to ensure that increased access is not achieved by
      undermining the additional protections to children provided by Subpart D.

PMID- 15467176
TI  - The formation of the American Society of Clinical Oncology and the development of
      a medical specialty, 1964-1973.
AB  - In April 1964, seven physicians met to discuss the formation of a new medical
      society for clinicians interested in the management of patients with cancer.
      Chemical warfare research during World War II had led to the advent of
      chemotherapeutic agents, a new, systemic approach toward cancer treatment. While
      skeptics questioned the benefits of chemotherapy, some internists viewed these
      drugs as promising new tools. Founders of the American Society of Clinical
      Oncology built their organization upon the importance, despite potential dangers,
      of utilizing chemotherapy as an essential component of cancer treatment, and
      positioned themselves as best qualified to manage the care of patients with
      cancer. The establishment of a new professional organization helped to anchor
      medical oncology as a distinct field during a time of increasing medical
      specialization in the United States. This essay examines the Society's early
      history within a broader context of the development of new chemical agents and
      cooperative groups, the formation of a new subspecialty, and increasing federal
      involvement in health care policy and funding, and describes the struggle of
      medical oncologists to solidify their authority over clinical cancer research and
      patient care.

PMID- 15467177
TI  - Pathways of innovation: a history of the first effective treatment for sickle
      cell anemia.
AB  - The promise of molecular medicine is the prevention and treatment of illness.
      Understanding the mechanism of the disease should allow one to "fix" it. For
      sickle cell anemia, however, knowledge of the biochemical basis of the disease
      was only partly responsible for finding a means of treating the disease--of equal
      value were hypotheses and conclusions generated from clinical observations. This
      article describes the research path that led to the first effective treatment for
      sickle cell anemia, hydroxy-urea. Rather than exemplifying the "bench-to-bedside"
      model commonly used to describe the process of therapeutic innovation, this
      history of this research reveals that the critical advances for the development
      of treatment came not from basic research, but instead from clinical and patient
      oriented research. Given that the linear approach is the prevailing paradigm of
      therapeutic innovation, this history is important because it indicates the
      inadequacy of this approach for a relatively straightforward single-gene mutation
      disease such as sickle cell anemia and suggests the need for multiple models of
      innovation for more complex diseases. Thus, this article questions the
      expectations of molecular medicine and the dominance of a linear model of
      therapeutic innovation, which often excludes or subordinates other models of
      developing treatments.

PMID- 15467178
TI  - The UGDP controversy: thirty-four years of contentious ambiguity laid to rest.
AB  - The University Group Diabetes Program (UGDP), launched in 1960, was an early
      placebo-controlled, multi-center clinical trial devised to determine which, if
      any, of the treatments for type 2 diabetes was efficacious. Because of an excess
      of cardiac deaths in patients treated with tolbutamide, a sulfonylurea drug,
      investigators terminated this limb of the study. This decision was met with
      strong resistance from the parent drug company and many in the medical community.
      Subsequent clinical studies both supported and conflicted with the UDGP findings,
      so that the controversy has persisted. A rationale for sulfonylurea-induced
      cardiotoxicity emerged with the observation that these drugs block ischemic
      preconditioning, a protective maneuver that reduces myocardial damage after
      temporary blockage of coronary blood flow; this action of sulfonylureas provided
      laboratory support for the UGDP findings. The development of newer sulfonylurea
      drugs that do not block ischemic preconditioning has rendered the UGDP
      controversy moot and has preserved a place for sulfonylureas in the treatment of
      type 2 diabetes.

PMID- 15467179
TI  - The role of anemia in congestive heart failure and chronic kidney insufficiency:
      the cardio renal anemia syndrome.
AB  - Anemia is a major problem in patients with chronic kidney insufficiency. The
      development of recombinant human erythropoietin has enabled physicians to correct
      this anemia. Although anemia has not been considered to be a common or important
      contributor to congestive heart failure, anemia of any cause can lead to cardiac
      damage and eventually congestive heart failure. Our joint renal-cardiac heart
      failure team found that anemia was indeed very common in congestive heart failure
      and was associated with severe, medication-resistant cardiac failure. Correction
      of the anemia with erythropoietin and intravenous iron led to a marked
      improvement in patients' functional status and their cardiac function, and to a
      marked fall in the need for hospitalization and for high-dose diuretics; renal
      function usually improved or at least stabilized. Subsequent investigations by
      others have confirmed many of our observations. We call this interrelationship
      between congestive heart failure, chronic kidney insufficiency, and anemia the
      Cardio-Renal Anemia syndrome. Treatment of the anemia in congestive heart failure
      may prove vital in preventing progression of both the heart failure and the
      associated renal disease.

PMID- 15467180
TI  - From the Great Barrier Reef to a "cure" for the flu: tall tales, but true.
AB  - How we discovered that sea birds on the Great Barrier Reef are riddled with
      influenza viruses, and how one of these led to a new drug now being used in the
      battle against the flu.

PMID- 15467181
TI  - The fundamentals of clinical discovery.
AB  - There is a widespread view that clinical research is failing to advance
      appropriately, particularly in comparison with other aspects of biomedical
      science. I argue that this is due in part to an inadequate understanding of how
      medical advance occurs. The common usage of such terms as basic or fundamental,
      or the uncritical use of the term model is unhelpful--unhelpful, in that such
      terms tend to presuppose a certain model of clinical advance that is unusual, and
      furthermore, because they tend to exaggerate the importance of research in
      subjects such as biochemistry and genetics at the expense of other areas. I
      suggest that much medical research is best viewed as a form of engineering rather
      than science, and that the knowledge base and research funding for the
      amelioration of disease needs to be much more broadly based than at present.

PMID- 15467182
TI  - Development of novel drug delivery system (DDS) technologies for proteomic-based
      drug development.
AB  - With the success of human genome projects, the focus of life science research has
      shifted to the functional and structural analyses of proteins, such as disease
      proteomics. These structural and functional analyses of expressed proteins in the
      cells and/or tissues are expected to contribute to the identification of
      therapeutically applicable proteins for various diseases. Thus, pharmaco
      proteomic based drug development for protein therapies is most noticed currently.
      However, there is a clinical difficulty to use almost bioactive proteins, because
      of their very low stability and pleiotropic actions in vivo. To promote pharmaco
      proteomic based drug development for protein therapies to various diseases, we
      have attempted to establish a system for creating functional mutant proteins
      (muteins) with desired properties, and to develop a site-specific polymer
      conjugation system for further improving the therapeutic potency of proteins. In
      this review, we are introducing our original protein-drug innovation systems
      mentioned above.

PMID- 15467183
TI  - New aspects of the blood-brain barrier transporters; its physiological roles in
      the central nervous system.
AB  - The blood-brain barrier (BBB) segregates the circulating blood from interstitial
      fluid in the brain, and restricts drug permeability into the brain. Our latest
      studies have revealed that the BBB transporters play important physiological
      roles in maintaining the brain milieu. The BBB supplies creatine to the brain for
      an energy-storing system, and creatine transporter localized at the brain
      capillary endothelial cells (BCECs) is involved in BBB creatine transport. The
      BBB is involved in the brain-to-blood efflux transport of the suppressive
      neurotransmitter, gamma-aminobutyric acid, and GAT2/BGT-1 mediates this transport
      process. BCECs also express serotonin and norepinephrine transporters. Organic
      anion transporter 3 (OAT3) and ASCT2 are localized at the abluminal membrane of
      the BCECs. OAT3 is involved in the brain-to-blood efflux of a dopamine
      metabolite, a uremic toxin and thiopurine nucleobase analogs. ASCT2 plays a role
      in L-isomer-selective aspartic acid efflux transport at the BBB.
      Dehydroepiandrosterone sulfate and small neutral amino acids undergo brain-to
      blood efflux transport mediated by organic anion transporting polypeptide 2 and
      ATA2, respectively. The BBB transporters are regulated by various factors, ATA2
      by osmolarity, taurine transporter by TNF-alpha, and L-cystine/L-glutamic acid
      exchange transporter by oxidative stress. Clarifying the physiological roles of
      BBB transport systems should give us important information allowing the
      development of better CNS drugs and improving our understanding of the
      relationship between CNS disorders and BBB function.

PMID- 15467184
TI  - Gene expression analysis in human gastric cancer cell line treated with
      trichostatin A and S-adenosyl-L-homocysteine using cDNA microarray.
AB  - Trichostatin A (TSA) and S-adenosyl-L-homocysteine (AdoHcy) have been reported to
      affect histone modifications. To investigate the effects of two drugs that can
      reportedly affect chromatin remodeling, we analyzed the gene expression profiles
      of TSA and AdoHcy in a gastric cancer cell line using 14 K cDNA microarray. The
      significant analysis of microarray (SAM) identified 98 and 43 differentially
      expressed genes in TSA and AdoHcy treated sets, respectively, and selected genes
      were functionally classified. In the gastric cancer cell line, genes related to
      cell communication, cell growth/maintenance, and morphogenesis were highly
      expressed with TSA, and genes with cell growth/maintenance, metabolism,
      oxidoreductase activity were upregulated with AdoHcy. Genes downregulated with
      TSA included those controlling the cell cycle, cell growth/proliferation, DNA
      binding, and metabolism, whereas genes involved in calcium signaling, cell
      growth/proliferation, and metabolism were downregulated with AdoHcy. Furthermore,
      we identified the genes commonly expressed in both drug treatments. Compared to
      TSA, AdoHcy did not induce apoptosis in the SNU-16 gastric cancer cell line, and
      RT-PCR was performed for selective genes to confirm the microarray data. This
      gene expression profile analysis with TSA and AdoHcy should contribute to a
      greater understanding of the molecular mechanism of chromatin remodeling and
      cancer, and provide candidate genes for further studies involving the roles of
      histone modifications in gastric cancer.

PMID- 15467185
TI  - Antioxidant activity of jionoside D from Clerodendron trichotomum.
AB  - The antioxidant property of jionoside D, isolated from Clerodendron trichotomum
      (Verbenaceae), was investigated. This compound showed scavenging activity of
      intracellular reactive oxygen species and of 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      radical, as well as lipid peroxidation inhibitory activity. This radical
      scavenging activity of jionoside D protected the cell viability of Chinese
      hamster lung fibroblast (V79-4) cells exposed H2O2. Furthermore, jionoside D
      reduced the apoptotic cells induced by H2O2, as demonstrated by the decreased
      number of sub G1 hypo-diploid cells and apoptotic body formation. However, it
      increased the activities of cellular antioxidant enzymes, superoxide dismutase
      and catalase. Taken together, these findings suggest that jionoside D, isolated
      from C. trichotomum, exhibits antioxidant properties.

PMID- 15467186
TI  - Characterization of a novel polypeptide N-acetylgalactosaminyltransferase
      (dGalNAc-T3) from Drosophila.
AB  - Polypeptide N-acetylgalactosaminyltransferases (GalNAc-transferases) catalyze the
      initial reaction of mucin-type O-glycosylation. Here, we report the first
      biochemical characterization of one of the Drosophila GalNAc-transferases,
      dGalNAc-T3. This enzyme retains conserved motifs essential for the catalytic
      activity, but is a novel isozyme in that it has several inserted sequences in its
      lectin-like domain. Northern hybridization analysis of this isozyme identified a
      2.5-kb mRNA in Drosophila larva. Biochemical characterization was carried out
      using the recombinant soluble dGalNAc-T3 expressed in COS7 cells. dGalNAc-T3,
      which required Mn2+ for the activity, had a pH optimum ranging from pH 7.5 to
      8.5, and glycosylated most effectively at 29-33 degrees C. Its Km for UDP-GalNAc
      was 10.7 microM, which is as low as that of mammalian isozymes. dGalNAc-T3
      glycosylated the peptides containing a sequence of XTPXP or TTAAP most
      efficiently. The enzyme was irreversibly inhibited by p
      chloromercuriphenylsulphonic acid, indicating the presence of essential Cys
      residues for the activity.

PMID- 15467187
TI  - Antipyretic, analgesic and anti-inflammatory activities of ketoprofen beta
      cyclodextrin inclusion complexes in animals.
AB  - Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) orally effective in
      treating fever, pain, and inflammation but gastrointestinal side effects were
      observed. Preparation of ketoprofen beta-cyclodextrin inclusion complexes was to
      increase the solubility and reduce the irritation. The complexes were prepared
      and preliminarily confirmed using X-ray diffraction and dissolution test.
      Antipyretic, analgesic and anti-inflammatory models were induced by 10% yeast
      using rabbits, 0.8% acetic acid using mice and 1% carrageenin using rats,
      respectively. Results showed that the dissolution rate of ketoprofen was
      significantly improved by complexation. X-Ray diffraction pattern of the
      complexes exhibited a diffuse pattern that differed from that of physical mixture
      of ketoprofen and beta-cyclodextrin. Ketoprofen markedly inhibited the fever
      reactions at a single dose of 2 mg/kg as follows: 64.53% (inhibition rate %) at 1
      h for ketoprofen, 73.04% at 1 h for ketoprofen beta-cyclodextrin inclusion
      complexes, respectively. Alleviating pain reaction rates following a single dose
      of 8 mg/kg at 20 min were 39.25% for the inclusion complexes and 26.72% for
      ketoprofen, respectively. Inhibition rates to rat edema following a single dose
      of 5 mg/kg at 1 h were 39.47% for the inclusion complexes and 23.86% for
      ketoprofen. Results for antipyretic, analgesic and anti-inflammatory activities
      showed that the rapid and stronger effects were found in the treatment group of
      ketoprofen beta-cyclodextrin inclusion complexes in comparison with those of free
      ketoprofen.

PMID- 15467188
TI  - Immune-enhancing effect of the Korean natural medicine WooKiEum.
AB  - WooKiEum (WKE) has been used for the purpose of the development of increased
      immune-system strength in Korea. In the present study, we examined the anti
      immobility effect of WKE on the forced swimming test (FST), and then measured
      blood biochemical parameters related to fatigue: glucose (Glc), blood urea
      nitrogen (BUN), lactic dehydrogenase (LDH), creatinine, and total protein (TP).
      WKE (0.1, 1 g/kg) was administered orally to mice for 7 d. After 2 d, the
      immobility time was decreased in the WKE-administered group. After 7 d, the
      immobility time was significantly decreased in the WKE-administered group (64.6+/
      9.0 s for 0.1 g/kg) in comparison with the control group (101.3+/-32.7 s). In
      addition, amount of Glc in the blood serum was increased, whereas the contents of
      BUN, LDH and TP decreased in the WKE-administered group. Next, we investigated
      the effect of WKE on the production of cytokines in a human T-cell line, MOLT-4
      cells and mouse peritoneal macrophages. WKE (1 mg/ml) significantly increased
      interferon (IFN)-gamma and TNF-alpha production compared with the media control
      (about 2.2-fold for IFN-gamma, about 1.7-fold for TNF-alpha, p<0.05) after 24 h.
      WKE increased the protein expression of IFN-gamma in MOLT-4 cells. These results
      suggest that WKE may be useful in immune function improvement.

PMID- 15467189
TI  - Oridonin induces a caspase-independent but mitochondria- and MAPK-dependent cell
      death in the murine fibrosarcoma cell line L929.
AB  - Oridonin, an active component isolated from Rabdosia rubescences, has been
      reported to exhibit antitumor effects, but little is known about its molecular
      mechanisms of action. In this study, the growth-inhibitory activity of oridonin
      for L929 cells is in time- and dose-dependent manner. After treatment with
      various concentrations of oridonin for 12 h, the majority of L929 cells underwent
      apoptosis as measured by an LDH activity-based assay. Although apoptotic bodies
      were observed in oridonin-treated L929 cells, DNA fragmentation as a hallmark of
      apoptosis was not found. The pan-caspase inhibitor, z-VAD, and caspase-3
      inhibitor, z-DEVD, sensitized L929 cells to oridonin, however, a PARP inhibitor
      (DPQ) effectively blocked oridonin-induced cell death. After 12 h treatment, PARP
      proenzyme was significantly cleaved. This result indicated that oridonin-induced
      L929 cell death required PARP degradation in a caspase-independent manner. In
      addition, an MEK/ERK inhibitor (PD98059) markedly blocked oridonin-induced cell
      death, whereas a p38 inhibitor (SB203580) and JNK inhibitor (SP600125) weakly
      protected the cells against death. Treatment with 41.2 microM oridonin for 12 h
      induced significant and persistent ERK activation and p38 inactivation in L929
      cells without evident changes in the protein levels. The responsiveness of ERK
      and p38 to oridonin suggests the involvement of these kinases in this apoptotic
      process. Moreover, oridonin increased the ratio of Bax/Bcl-2 protein expression,
      whereas it had no effect on the expression of Bcl-xL. These results indicate that
      regulation of the Bcl-2 and MAPK families maybe the effector mechanisms of
      oridonin-induced L929 cell death, independent of the caspase pathway.

PMID- 15467190
TI  - Immunogenic comparison of two coupling methods of marine polysaccharide to bovine
      serum albumin.
AB  - Two conjugates of marine polysaccharide (MPS) and bovine serum albumin (BSA) were
      prepared using two methods, periodate oxidation and reductive amination, with the
      intent of enhancing its immunogenicity. Sera samples from Balb/c mice immunized
      with the products named MPS-BSAp and MPS-BSAr respectively were evaluated by
      enzyme-linked-immunosorbent assay (ELISA). The results showed that mice immunized
      with MPS-BSAp produced antibodies not against MPS but rather against MPS-BSAp,
      while the mice immunized with MPS-BSAr produced high titer antibodies only
      specific for MPS. The difference was attributed to the fact that the epitopes of
      MPS had been changed in the coupling process by periodate oxidation. A mouse
      immunized with MPS-BSAr was chosen to prepare monoclonal antibodies (mAbs)
      specific for polysaccharide MPS. A hybridoma cell line that secreted monoclonal
      antibody recognizing specifically polysaccharide MPS was established.

PMID- 15467191
TI  - C-reactive protein-induced expression of CD40-CD40L and the effect of lovastatin
      and fenofibrate on it in human vascular endothelial cells.
AB  - Inflammation plays a pivotal role in the formation of atherosclerosis. In
      addition to being a risk marker for cardiovascular diseases, the role of C
      reactive protein (CRP) in atherogenesis has been supported by more recent data.
      CD40-CD40L system is proven to be an important mediator of several auto-immune
      and chronic inflammation diseases. Interruption of CD40-CD40L signaling pathway
      not only reduces the initiation and progression of atherosclerotic lesions, but
      also modulates plaque architecture. By using a flow cytometry and western
      blotting, we found that incubation of human umbilical vein endothelial cells
      (HUVECs) with CRP resulted in a time- and dose-dependent increase in the cell
      surface expression of CD40 and CD40L. In addition, CRP (25 microg/ml) increased
      gelatinolytic activities of MMP-2 and MMP-9. Anti-CD40 antibody significantly
      reversed the upregulated activities of MMP-2 and MMP-9 induced by CRP with
      gelatin zymography. Furthermore, lovastatin (10(-7), 10(-6), 10(-5) mol/l) and
      fenofibrate (5 x 10(-5), 10(-4), 2 x 10(-4) mol/l) significantly diminished the
      expression of CD40, CD40L and gelatinase activities (MMP-2, MMP-9) induced by CRP
      in HUVECs. In conclusion, our data provide evidence to support the direct pro
      inflammatory effects of CRP via CD40-CD40L signaling pathway involved in the
      pathogenesis of atherosclerosis, and lovastatin and fenofibrate possess anti
      inflammatory effects independent of their lipid-lowering action.

PMID- 15467192
TI  - Carbachol-induced membrane ruffling and its desensitization in rat basophilic
      leukemia (RBL-2H3) cells transfected with m3 muscarinic acetylcholine receptors.
AB  - The changes in the reorganization of actin filaments during desensitization of
      secretion were investigated by transfecting RBL-2H3 cells with cDNA encoding the
      human m3 muscarinic acetylcholine receptors (RBL-m3 cells). Incubation of RBL-m3
      cells with 10-100 microM carbachol in Ca2+ -free medium developed membrane
      ruffling. When the cells were desensitized under the condition where
      desensitization of carbachol-induced secretion occurred, desensitized cells
      failed to develop membrane ruffling with the subsequent addition of carbachol.
      These results suggest that m3 muscarinic receptor-mediated desensitization of
      secretion involves negative regulation of actin reorganization leading to
      membrane ruffling.

PMID- 15467193
TI  - Differential effects of beta2-adrenoceptor desensitization on the IgE-dependent
      release of chemical mediators from cultured human mast cells.
AB  - In the present study, we examined the inhibitory effects of the beta2
      adrenoceptor agonists isoproterenol, salbutamol, fenoterol, and clenbuterol, on
      the release of chemical mediators from cultured human mast cells after prolonged
      treatment with the agonists. Although preincubation of sensitized mast cells for
      10 min with beta2-adrenoceptor agonists potently inhibited mediator release,
      prolongation of the preincubation period up to 240 min attenuated the inhibition.
      The attenuation of histamine release inhibition was potent when compared with
      that of prostaglandin D2 (PGD2) and cysteinyl leukotriene (LT) release
      inhibition. In contrast, forskolin inhibited mediator release and the inhibition
      increased gradually in proportion to the preincubation period. The reduced
      inhibition by the beta2-adrenoceptor agonists was compensated for by simultaneous
      treatment with cholera toxin. The beta2-adrenoceptor agonists elevated
      intracellular cAMP levels after 10-min incubation and the elevated levels were
      almost comparable to those after 240-min incubation. Forskolin elevated the
      intracellular cAMP levels more potently after incubation for 240 min than after
      10 min. When mast cells were incubated for 3 d with the beta2-adrenoceptor
      agonists, similar attenuation of mediator release inhibition was observed.
      Elevation of intracellular cAMP levels was also attenuated, although beta2
      adrenoceptor mRNA expression was potentiated. The present results collectively
      indicate that the attenuation of mediator release inhibition by beta2
      adrenoceptor agonists under the present experimental conditions involves
      uncoupling between beta2-adrenoceptors and Gs proteins. Furthermore, the beta2
      adrenoceptor desensitization causes differential attenuating effects on the
      inhibition of histamine, PGD2, and LT release, suggesting that downstream events
      involved in each inhibitory pathway have different sensitivity to receptor
      desensitization.

PMID- 15467194
TI  - The inhibitory effect of intestinal bacterial metabolite of ginsenosides on CYP3A
      activity.
AB  - The intestinal bacterial metabolites of ginsenosides are responsible for the main
      pharmacological activities of ginseng. The purpose of this study was to find
      whether these metabolites influence hepatic metabolic enzymes and to predict the
      potential for ginseng-prescription drug interactions. Utilizing the probe
      reaction of CYP3A activity, testosterone 6beta-hydroxylation, the effects of
      derivatives of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol families on CYP3A
      activity in rat liver microsomes were assayed. Our results showed that
      ginsenosides from the 20(S)-protopanaxadiol and 20(S)-protopanaxatriol family
      including Rb1, Rb2, Rc, Compound-K, Re, and Rg1 had no inhibitory effect, whereas
      Rg2, 20(S)-panaxatriol and 20(S)-protopanaxatriol exhibited competitive
      inhibitory activity against CYP3A activity in these microsomes with the
      inhibition constants (Ki) of 86.4+/-0.8 microM, 1.7+/-0.1 microM, and 3.2+/-0.2
      microM, respectively. This finding demonstrates that differences in their
      chemical structure might influence the effects of ginsenosides on CYP3A activity
      and that ginseng-derived products might have potential for significant ginseng
      drug interactions.

PMID- 15467195
TI  - Wogonin inhibits ischemic brain injury in a rat model of permanent middle
      cerebral artery occlusion.
AB  - The present study evaluated the effect of wogonin, a flavonoid originated from
      the root of Scutellaria baicalensis GEORGI, on focal ischemic brain injury in
      rats. Focal brain ischemia was induced by the permanent occlusion of middle
      cerebral artery (pMCAO) for 24 h with a silicone rubber cylinder inserted through
      the right internal carotid artery. We found that wogonin, intraperitoneally
      administered at a dosage of 20 mg/kg at 30 min before and 4 h after the surgery,
      reduced the pMCAO-induced infarct areas in the cerebral cortex as well as in the
      striatum. The total volume of infarction was significantly reduced by the
      treatment with wogonin. In addition, wogonin was found to significantly improve
      the pMCAO-induced behavioral deficits at 24 h after the surgery. Taken together,
      these results demonstrate that wogonin inhibits ischemic brain injury and
      improves behavioral dysfunction caused by pMCAO. These findings, along with
      previous reports demonstrating the neuroprotective effects of wogonin, provide
      strong pharmacological basis for the use of wogonin or Scutellaria baicalensis in
      the treatment of stroke.

PMID- 15467196
TI  - Overproduction of N(epsilon)-(carboxymethyl)lysine-induced neovascularization in
      cultured choroidal explant of streptozotocin-diabetic rat.
AB  - Action of N(epsilon)-(carboxymethyl)lysine (CML) adduct, an advanced glycation
      end product, was investigated on neovascularization of cultured choroidal
      explants in streptozotocin (STZ)-diabetic rat. The choroidal explants of early (4
      weeks after an injection of 60 mg/kg STZ) and advanced (8 months after the STZ
      injection) diabetic rats, and age-matched normal rats were cultured in fibrin gel
      with Dulbecco's modified Eagle medium containing fetal bovine serum. The number
      of budded microvessel-like structures was counted and used as an index of in
      vitro neovascularization. Choroidal explants in the early diabetic stage released
      vascular endothelial growth factor (VEGF) and tended to increase tumor necrosis
      factor (TNF) alpha and platelet-derived growth factor (PDGF)-B, and concomitantly
      facilitated growth of sprout and buds, compared to the normal control. When
      choroidal explants were stimulated with CML-human serum albumin (HSA), its
      releasing effect was in the order VEGF>TNFalpha>PDGF-B. CML-HSA and CML-bovine
      serum albumin augmented the neovascularization in the cultured diabetic explant
      and their actions did not virtually differ. A monoclonal anti-CML antibody (6D12)
      inhibited the neovascularization in the advanced diabetes greater than that in
      the early diabetes. Inhibitory actions of anti-VEGF and anti-TNFalpha antibodies
      on the neovascularization were similar to that of the anti-CML antibody in the
      diabetes. In conclusion, CML adducts were accumulated and over-produced the
      actions of VEGF, TNFalpha and PDGF-B in the choroidal explant during diabetes in
      an age-dependent manner. TNFalpha and VEGF are likely to play a predominant role
      for the CML-induced choroidal neovascularization.

PMID- 15467197
TI  - In vitro confirmation of selegiline N-oxidation by flavin-containing
      monooxygenase in rat microsome using LC-ESI MS.
AB  - In order to investigate the conversion of selegiline (SG), a drug used in the
      treatment of Parkinson's disease, to selegiline N-oxide (SGO) as a major
      metabolic pathway for SG, rat liver microsomal incubations were carried out in
      vitro in the presence of NADPH. SG was transformed into SGO in vitro as described
      in our previous human in vivo experiment. In the kinetic studies, the Vmax/Km
      value of the N-oxidation at pH 8 was found to be approximately four times greater
      than that at pH 7.4. The N-oxidation was also found to be inhibited by
      methimazole, an inhibitor of the flavin-containing monooxigenase (FMO) rather
      than by SKF 525A, an inhibitor of cytochrome P450s, and stimulated approximately
      two times by n-octylamine, an stimulator of FMO. Moreover, the N-oxidation
      activity remained almost unchanged in the presence of NADPH even after heating at
      50 degrees C for a few minutes. The present data demonstrate that the N-oxidation
      of SG to SGO is principally mediated by FMO.

PMID- 15467198
TI  - Antimicrobial activity of some pentacyclic triterpenes and their synthesized 3-O
      lipophilic chains.
AB  - The major metabolites of Diopsyros melanoxylon viz. amyrins and ursolic acid and
      their lipophilic 3-O-fatty acid ester chains (C12-C18), which are synthesized now
      under mild esterification conditions in excellent yields (80-95%), were evaluated
      for their antimicrobial activity against a series of Gram positive and Gram
      negative bacteria. Significantly these compounds were found to exhibit potent
      activity against Gram negative bacteria Pseudomonas syringae (ATCC #13457) and
      fairly good activity against Gram positive bacteria, Bacillus sphaericus (ATCC
      #14577) and Bacillus subtilis (ATCC #6051).

PMID- 15467199
TI  - Metabolic activities of ginsenoside Rb1, baicalin, glycyrrhizin and geniposide to
      their bioactive compounds by human intestinal microflora.
AB  - To evaluate the pharmacological actions of herbal medicines, metabolic activities
      of herbal medicine components, ginsenoside Rb1, glycyrrhizin, geniposide and
      baicalin to their bioactive compounds compound K, 18beta-glycyrrhetic acid,
      genipin and baicalein by fecal specimens were measured. Their metabolic
      activities were 646.1+/-591.4, 29.4+/-51.7, 926.3+/-569.6 and 3884.6+/-1400.1
      micromol/h/g, respectively. The profiles of these metabolic activities of
      baicalin and ginsenoside Rb1 were not significantly different to those of water
      extracts of Scutellariae Radix and Ginseng Radix. None of the metabolic
      activities tested were different between males and females, or between ages.
      However, the difference in these metabolic activities in individuals was
      significant. These results suggest that the human intestinal microflora enzymes
      that convert herbal components to their bioactive compounds may be used as
      selection markers of responders to traditional medicines.

PMID- 15467200
TI  - Effects of ellagic acid and 2-(2,3,6-trihydroxy-4-carboxyphenyl)ellagic acid on
      sorbitol accumulation in vitro and in vivo.
AB  - Caesalpinia ferrea MART. (Leguminosae) called as Juca is one of the medicinal
      plants in Brazil used for diabetes. From the fruits of this plant, ellagic acid
      (EA) and 2-(2,3,6-trihydroxy-4-carboxyphenyl)ellagic acid (TEA) have been
      recently isolated as aldose reductase (AR) inhibitors. In this study, we examined
      to prove the inhibitory activity against AR of EA and TEA in vitro, and EA in
      vivo by measurement of the accumulation of sorbitol, which is the product of
      glucose reduction catalyzed by AR. TEA was not examined in vivo because of its
      shortage of yield from the fruits. EA and TEA significantly and dose-dependently
      inhibited sorbitol accumulation in erythrocytes, lens and sciatic nerve under
      incubating with glucose in vitro. EA at a dose of 75 mg/kg/d showed the most
      potent inhibition of sorbitol accumulation in erythrocytes, lens and sciatic
      nerve at 50, 75 and 100 mg/kg/d in vivo. These results suggest that the
      inhibitory activity of EA against AR causes to inhibit sorbitol accumulation by
      in vitro and in vivo experiments. EA is distributed in fruits and vegetables, so
      that taking them might be able to relieve diabetic complications.

PMID- 15467201
TI  - Anti-inflammatory and anti-nociceptive effects of the methanol extract of Fomes
      fomentarius.
AB  - In an attempt to find bioactive natural products with an anti-inflammatory
      activity, we evaluated the effects of the methanol extract of Fomes fomentarius
      (MEFF) on in vivo anti-inflammatory and anti-nociceptive activities. MEFF (50,
      100 mg/kg/d, p.o.) reduced acute paw edema induced by carrageenin in rats, and
      showed MEFF analgesic activity, as determined by an acetic acid-induced writhing
      test and a hot plate test in mice. To investigate the mechanism of the anti
      inflammatory action of MEFF, we examined the effect of MEFF on lipopolysaccharide
      (LPS)-induced responses in murine macrophages cell line RAW 264.7. MEFF potently
      inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), and tumor
      necrosis factor-alpha (TNF-alpha) in LPS-stimulated RAW 264.7 macrophages.
      Consistent with these observations, inducible NO synthase (iNOS) and
      cyclooxygenase-2 (COX-2) levels were reduced by MEFF in a dose-dependent manner.
      Furthermore, MEFF suppressed nuclear factor-kappaB (NF-kappaB) activation in LPS
      stimulated RAW 264.7 macrophages. These findings suggest that the anti
      inflammatory and anti-nociceptive properties of the methanol extract of MEFF may
      result from the inhibition of iNOS and COX-2 expression through the down
      regulation of NF-kappaB binding activity.

PMID- 15467202
TI  - Saucernetin-8 isolated from Saururus chinensis induced the differentiation of
      human acute promyelocytic leukemia HL-60 cells.
AB  - The present work was performed to investigate the effects of saucernetin-8 on
      proliferation and differentiation of human leukemia HL-60 cells as well as the
      underlying mechanisms for these effects. Saucernetin-8 exhibited a potent
      antiproliferative activity against HL-60 cells. This compound was also found to
      be a potent inducer of differentiation in human leukemia derived HL-60 cells
      through the examination of differentiation markers, as assessed by nitroblue
      tetrazolium reduction test, esterase activity assay, phagocytic activity assay,
      morphology change, and expression of CD14 and CD66b surface antigens. These
      results suggest that saucernetin-8 induces the differentiation of human leukemia
      cells to granulocytes and monocytes/macrophages lineage. Moreover, DNA flow
      cytometry indicated that saucernetin-8 induced a G1 phase arrest of HL-60 cells.
      The protein and mRNA expression levels of p21 were up-regulated during
      saucernetin-8-dependent HL-60 cell differentiation, whereas the level of c-myc
      was down-regulated. Taken together, our results suggest that saucernetin-8 may
      have potential as a therapeutic agent in human leukemia.

PMID- 15467203
TI  - Pharmacological properties of traditional medicine (XXIX): effect of Hange
      shashin-to and the combinations of its herbal constituents on rat experimental
      colitis.
AB  - Hange-shashin-to (HST) has been used as an herbal formula to treat inflammatory
      ulcerative gut diseases complicated with psychoneurosis in Japanese traditional
      Kampo medicine. The aim of the present study is to clarify anti-colitic effect of
      HST using a model of colitis induced by intracolonic instillation of 2,4,6
      trinitrobenzene sulfonic acid (TNBS) in rats, and to evaluate the pharmaceutical
      properties of its herbal components. The colonic damage was elucidated by
      macroscopic damage scores, colon wet weight and area of mucosal necrosis. Orally
      administered HST significantly reduced the colonic damage. Other rats were orally
      treated with single-component berberine (BE), baicalin (BA), glycyrrhizin (GL) or
      saponin fraction of ginsenosides (GS), or with the mixture (TL) of BA, BE, GL and
      GS, or with the combinations of BA plus BE (BA-BE), or that of GL plus GS (GL
      GS). Oral treatment of TL ameliorated colitis observations. However, no effects
      were found in the treatment of single-component BA, BE, GL or GS, whereas the GL
      GS combination ameliorated the colitis. These results suggest that HST might
      suppress inflammatory bowel disease (IBD) and imply that there will be a
      potential benefit in the traditionally derived herbal combination.

PMID- 15467204
TI  - Induction of apoptosis by Saussurea lappa and Pharbitis nil on AGS gastric cancer
      cells.
AB  - We performed this study to understand the molecular basis underlying the
      antitumor effects of Saussurea lappa, Pharbitis nil, Plantago asiatica and
      Taraxacum mongolicum, which have been used for herbal medicinal treatments
      against cancers in East Asia. We analyzed the effects of these medicinal herbs on
      proliferation and on expression of cell growth/apoptosis related molecules, with
      using an AGS gastric cancer cell line. The treatments of Saussurea lappa and
      Pharbitis nil dramatically reduced cell viabilities in a dose and time-dependent
      manner, but Plantago asiatica and Taraxacum mongolicum didn't. FACS analysis and
      Annexin V staining assay also showed that both Saussurea lappa and Pharbitis nil
      induce apoptotic cell death of AGS. Expression analyses via RT-PCR and Western
      blots revealed that Saussurea lappa, but not Pharbitis nil, increased expression
      of the p53 and its downstream effector p21Waf1, and that the both increased
      expression of apoptosis related Bax and cleavage of active caspase-3 protein. We
      also confirmed the translocation of Bax to mitochondria. Collectively, our data
      demonstrate that Saussurea lappa and Pharbitis nil induce growth inhibition and
      apoptosis of human gastric cancer cells, and these effects are correlated with
      down- and up-regulation of growth-regulating apoptotic and tumor suppressor
      genes, respectively.

PMID- 15467205
TI  - Melanogenesis stimulation in murine B16 melanoma cells by Piper nigrum leaf
      extract and its lignan constituents.
AB  - A methanolic extract from the leaves of Piper nigrum L. showed a significant
      stimulatory effect on melanogenesis in cultured murine B16 melanoma cells.
      Activity-guided fractionation of the methanolic extract led to the isolation of
      two known lignans, (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4
      desmethylenedioxycubebin (2), together with a new lignan, (-)-3
      desmethoxycubebinin (3). Among these lignans, 1 and 2 showed a significant
      stimulatory activity of melanogenesis without any significant effects on cell
      proliferation.

PMID- 15467206
TI  - Methanol extracts of Hamelia patens containing oxindole alkaloids relax KCl
      induced contraction in rat myometrium.
AB  - Hamelia patens JAQC. (Rubiaceae) is a medicinal bush widely distributed in
      tropical areas of the American continent. It is used in Mexican Traditional
      Medicine for the treatment of menstrual disorders, therefore suggesting that its
      chemical constituents may have some effect on myometrium contractility.
      Physiological effects might differ due to quantitative variations in the content
      of alkaloids arising from its wide geographical distribution. To test this
      hypothesis, the content of oxindole alkaloids in methanol extracts of five
      different samples collected in Mexico was quantified by GC-MS. Each extract was
      assayed on contractility of estrogen-primed rat myometrium. Variations in the
      content of alkaloids were observed among the different samples. All samples
      relaxed in a concentration-dependent manner the high KCl-induced contraction in
      rat myometrium. Those which lack rumberine and/or maruquine displayed a higher
      relaxant effect than samples containing them, suggesting that these alkaloids
      might counteract the effects of isopteropodine. However, in contrast with
      verapamil, Hamelia patens metanol extracts are poor relaxants.

PMID- 15467207
TI  - Activation of phenylpropanoid metabolism in sesame by over-expression of carrot
      calmodulin gene.
AB  - Transgenic sesame (Sesamum schinzianum ASCH.) was produced by Agrobacterium
      mediated transfection of a carrot calmodulin gene, cam-4, which was specifically
      expressed upon the contact of carrot cells with oligogalacturonide elicitor.
      Coding region of cam-4 was ligated to the downstream of 35S promoter of
      cauliflower mosaic virus and subcloned into pMATGBO-DB3.1. A. tumefaciens 4404
      was transformed with the constructed vector, and the crown gall tissues formed in
      the sesame seedlings were transferred onto appropriate media to obtain the re
      differentiated plants. The reverse-transcription polymerase chain reaction
      followed by Southern blot analysis revealed that cam-4 gene was appreciably
      expressed in the transgenic plants. Activities of two key enzyme regulating
      phenylpropanoid metabolisms, phenylalanine ammonia-lyase and caffeic acid O
      methyltransferase, and the contents of phenolic compounds in the transformed
      sesame were markedly elevated as compared with those of the control. These
      results suggest that the over-expression of cam-4 gene enhances the biosynthetic
      activities of phenylpropane derivatives in the transformed sesame plants.

PMID- 15467208
TI  - Optimization of sustained-release propranolol dosage form using factorial design
      and response surface methodology.
AB  - The purpose of this study was to develop propranolol extended release
      formulations containing hydroxypropylmethylcellulose (HPMC). The results indicate
      that the drug release from the tablet form containing a high amount of HPMC was
      incomplete, and avicel addition could increase the release percent at a later
      stage. In order to readily obtain an optimal formulation, response surface
      methodology and multiple response optimization utilizing a quadratic polynomial
      equation was used. The model formulations were prepared according to a factorial
      design. The effects of causal factors including the HPMC/drug ratio (X1) and
      avicel level (X2), on drug release were also measured. The drug release
      percentage at 1.5, 4, 8, 14 and 24 h were the target response and were restricted
      to not more than 25%, 35-50%, 55-70%, 75-90%, and 95-110%, respectively. The
      results showed that the optimized formulation provided a dissolution pattern
      equivalent to the predicted curve, which indicated that the optimal formulation
      could be obtained using response surface methodology. The mechanism of drug
      release from HMPC matrices tablets followed quasi-Fickian diffusion.

PMID- 15467209
TI  - Classification of loratadine based on the biopharmaceutics drug classification
      concept and possible in vitro-in vivo correlation.
AB  - Loratadine was studied both in vitro and in vivo (in healthy humans) to classify
      it according to the Biopharmaceutics Classification System (BCS) in order to gain
      more understanding of the reasons for its highly variable nature with respect to
      plasma time profiles, and to determine the most appropriate dissolution test
      conditions for in vitro assessment of the release profile of the drug from solid
      dose forms. Based on the solubility of loratadine determined under various pH
      conditions and its permeability through Caco-2 monolayers, loratadine was
      classified as a Class II drug. Plasma profiles were predicted by convolution
      analysis using dissolution profiles obtained under various pH and hydrodynamic
      conditions as the input function and plasma time data obtained from a syrup
      formulation as the weighting function. The predicted profiles based on
      dissolution studies done at gastric pH values were in reasonable agreement with
      the mean bio-data suggesting dissolution testing should be done at gastric pH
      values. However, the bio-data were highly variable and it is suggested this may
      be due, at least in part, to high individual gastric pH variability and
      dissolution occurring in the intestine on some occasions, and therefore,
      dissolution testing should also be done in simulated intestinal fluid.

PMID- 15467210
TI  - Ameliorative effects of soy 11S protein on liver damage and hyperlipidemia in
      alcohol-fed rats.
AB  - This study sought to investigate the ameliorating effects of soy 11S protein on
      the impacts of alcohol consumption in rat hepatocytes and in reducing total
      cholesterol levels and total lipid levels in the serum. Liver histology and the
      clinically important enzyme markers (Aspartate Aminotransferase: AST and Alanine
      Aminotransferase: ALT) of rats, administered with both alcohol and soy 11S
      protein treatments, were compared with those in the control group. The treatment
      regimen (11S soy protein extract) significantly reduced serum ALT and AST levels,
      indicating the hepato-protective effects of soy 11S protein. Furthermore, total
      cholesterol and total lipid levels were significantly reduced. In addition to
      preventing the presence of lipid droplets and secondary lysosomes, electron
      microscopy indicated that the administration of the soy 11S protein treatment
      preserved important hepatocyte structures. These results indicate that soy 11S
      protein can positively mediate the effects of alcohol on hepatocytes and general
      liver functions.

PMID- 15467211
TI  - Nonlinear mixed effects model analysis of the pharmacokinetics of metoprolol in
      routinely treated Japanese patients.
AB  - This study was performed to estimate the mean pharmacokinetic parameters of
      routinely administered metoprolol in middle-aged and elderly Japanese patients.
      Whole blood concentration data (65 samples) at steady-state following repetitive
      administration to 34 patients were analyzed using a nonlinear mixed effects
      model. A one-compartment model was parameterized in terms of oral clearance
      (CL/F) and apparent volume of distribution (V/F). We evaluated the effect of
      polymorphic alleles (CYP2D6*2, CYP2D6*10, CYP2C19*2 and CYP2C19*3), age, gender,
      and heart failure on the pharmacokinetic parameters of metoprolol. The CL/F value
      in patients homozygous for the CYP2D6*10 allele was 64% lower than that in
      patients with a CYP2D6*1/*1 or *1/*2 genotype. The CL/F value in older (>70 years
      old) patients was 26% lower than that in younger (< or = 70 years old) patients.
      In addition, the V/F value in patients homozygous for the CYP2D6*10 allele was
      25% lower than that in patients with the CYP2D6*1/*1 or *1/*2 genotype. On the
      other hand, the CYP2C19 genotype, gender, and heart failure showed no significant
      effects on the pharmacokinetics of metoprolol. The results suggest that the
      pharmacokinetic variability of metoprolol in Japanese extensive metabolizers of
      CYP2D6 is very large, probably because CYP2D6*10 is responsible not only for the
      decreased systemic clearance (CL) but also for the increased bioavailability (F)
      of the drug.

PMID- 15467212
TI  - Apocynum venetum extract does not induce CYP3A and P-glycoprotein in rats.
AB  - We investigated the effect of Apocynum venetum L. extract (AV) on the activity of
      cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp). The plasma concentration of
      nifedipine (NF), which is a substrate for CYP3A, did not change after oral
      administration with AV (3.3 mg/kg). Also, AV (3.3 and 33 mg/kg) did not affect
      the intestinal absorption of NF. In the rats treated with multiple
      administrations (15 mg/kg/d) of St. John's wort extract (SJW) for 2 weeks, the
      plasma concentration of NF after oral administration was significantly decreased.
      On the other hand, there was no significant differences in the pharmacokinetic
      parameters of NF between AV-treated (3.3 mg/kg/d) and none-treated rats.
      Furthermore, the intestinal absorption of methylprednisolone, which is a
      substrate for P-gp, was not affected by AV treatment for 2 weeks. These results
      suggest that, unlike SJW, the recommended dose of AV (3.3 mg/kg/d) would not
      influence hepatic CYP3A and intestinal P-gp in rats.

PMID- 15467213
TI  - Secretion mode and subcellular localization of human interferon-beta exogenously
      expressed in porcine renal epithelial LLC-PK1 cells.
AB  - We have investigated the secretion polarity of human interferon-beta (HuIFN-beta)
      exogenously expressed in the porcine renal proximal tubule cell line, LLC-PK1. In
      these cells, stably expressed HuIFN-beta was secreted to the apical and
      basolateral sides. However, when transiently expressed by apical lipofection,
      HuIFN-beta was secreted to both cell sides, while basolateral-preferential
      secretion was seen for basal transfection. Confocal imaging using enhanced green
      fluorescent protein (EGFP)-tagged HuIFN-beta revealed no difference in the
      subcellular distribution in either of the chimeric protein-expressing cells
      examined. These results suggest that the secretion polarity of HuIFN-beta is
      regulated by a post trans-Golgi network in a cell type-dependent manner.

PMID- 15467214
TI  - Proteoglycan isolated from Phellinus linteus induces toll-like receptors 2- and 4
      mediated maturation of murine dendritic cells via activation of ERK, p38, and NF
      kappaB.
AB  - Mushroom polysaccharides are increasingly being utilized to treat a wide variety
      of diseases. Phellinus linteus proteoglycan (PL) has been reported to have anti
      tumor and immunomodulatory properties. However, the cellular and molecular
      mechanism underlying its therapeutic effect is poorly understood. In this study,
      we investigated whether PL induces the phenotypic and functional maturation of
      murine bone marrow-derived dendritic cells (DC) and the possibility that Toll
      like receptors (TLRs), which are known to be involved in immune-related
      responses, may be the receptor(s) of PL. The expression of surface molecules,
      including major histocompatibility complex (MHC) class II and CD86, increased on
      DC that were stimulated in a dose-dependent manner with PL, in comparison with
      unstimulated DC. Furthermore, PL increases the production of IL-12 by DC, as well
      as the IL-2 secretion and proliferation of allogeneic T cells. In addition, the
      activities of PL on DC were significantly reduced by treating the cells with anti
      TLR2 or anti-TLR4 antibody (Ab) prior to PL, suggesting that both of them are
      possible receptors of PL. Also, maturation of DC by PL was able to directly
      activate mitogen-activated protein kinases (MAPKs), such as ERK1/2 and p38, and
      the nuclear transcription factor NF-kappaB p65. Also, the pretreatment of DC with
      inhibitors of NF-kappaB p65, and ERK and p38 MAPK signal pathways inhibited PL
      induced up-regulation of surface molecules, such as MHC class II and CD86, and IL
      12 production. Our results demonstrated that PL stimulation could induce the
      phenotypic and functional maturation of DC via TLR2 and/or TLR4 mediated-NF
      kappaB, ERK and p38 MAPK signal pathways.

PMID- 15467215
TI  - 17alpha-hydroxylase/C17-20 lyase cytochrome P450 mRNA expressions and enzyme
      activities during the development of arthritis in collagen-induced arthritis
      mice.
AB  - In our previous study, we have investigated the serum levels of
      dehydroepiandrosterone (DHEA) in type II collagen (CII)-induced arthritis (CIA)
      mice. During the study, we found that in normal control mice, serum levels of
      DHEA in the latter half of the experimental period (13-16 weeks old) were
      significantly lower than those at the beginning of the experiment (10 weeks old).
      However, in CIA mice, such decreases were not observed by CII treatment. To
      examine the cause of the retention of DHEA during the development of arthritis in
      CIA mice in this study, 17alpha-hydroxylase/C17-20 lyase P450 (CYP17) mRNA
      expressions were measured by real time RT-PCR and the CYP17 enzyme activities
      were investigated in the liver and testis on days 6, 13, 28 and 48 after CII
      treatment in DBA/1J mice. There were no significant differences of CYP17
      expressions in the liver between control and CIA mice at each experimental day,
      while a significant increase of expression in the testis of CIA mice was observed
      on day 48. On the other hand, CYP17 enzyme activities on days 28 and 48 in testis
      microsome (Mc) from the CIA mice were significantly higher than those of the
      control on the same day, while no significant differences of activities in liver
      Mc were observed between the CIA and control mice. These findings suggested that
      the cause of the retention of DHEA on days 28 and 48 after CII treatment may be
      the increase of CYP17 expression and the enzyme activities in the testis.

PMID- 15467216
TI  - Biological activity of beta-dolabrin, gamma-thujaplicin, and 4-acetyltropolone,
      hinokitiol-related compounds.
AB  - Beta-dolabrin, gamma-thujaplicin, and 4-acetyltropolone, the components of Aomori
      Hiba (Thujopsis dolabrata SIEB. et ZUCC. var. hondai MAKINO), showed antifungal
      activity on seven kinds of plant-pathogenic fungi, antibacterial activity against
      two kinds of Legionella sp., and in vitro cytotoxic effect on murine P388
      lymphocytic leukemia cell line. Firstly, beta-dolabrin, gamma-thujaplicin and 4
      acetyltropolone had clear antifungal activity against seven kinds of plant
      pathogenic fungi tested. In particular, beta-dolabrin and 4-acetyltropolone
      showed strong antifungal activity against Pythium aphanidermatum IFO 32440, with
      minimum inhibitory concentration (MIC) values of 6.0 microg/ml. Secondly, beta
      dolabrin, gamma-thujaplicin and 4-acetyltropolone had obvious growth-inhibitory
      effect on two kinds of Legionella sp. 4-Acetyltropolone especially had strong
      antibacterial activity toward Legionella pneumophila SG 1, and its MIC value was
      3.1 microg/ml. These three compounds showed cytotoxic effects against murine P388
      lymphocytic leukemia cell line in vitro. The cytotoxic effect of three compounds
      in the murine P388 lymphocytic leukemia cell line were clear when cell growth was
      measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) method. At 48 h after treatment, gamma-thujaplicin and 4-acetyltropolone at
      0.63 microg/ml inhibited cell growth of murine P388 lymphocytic leukemia by 85%
      and 65%, respectively. At the same time after treatment, the growth of the murine
      P388 lymphocytic leukemia cell line was completely suppressed by the three
      compounds at concentrations higher than 5.0 microg/ml. Among these three
      compounds, gamma-thujaplicin had the strongest cytotoxic activity on the growth
      of this tumor cell line in vitro.

PMID- 15467217
TI  - Pentoxifylline inhibits tumor necrosis factor-alpha induced synthesis of
      complement component C3 in human endothelial cells.
AB  - Vascular endothelium is a major target for the inflammatory damage that occurs
      with multiple organ dysfunction associated with sepsis and other trauma. The
      growing appreciation of endothelium as a target of inflammation has obscured the
      importance of these cells as a source of inflammatory mediators. In the following
      study we evaluated the ability of tumor necrosis factor-alpha (TNF) to induce the
      synthesis of complement component C3 in human umbilical vein endothelial cells
      (HUVEC) and whether pentoxifylline (PTX) could reduce C3 expression. Confluent
      monolayers of HUVEC were treated with increasing concentrations of TNF with and
      without two concentrations of PTX. Concentrations of C3 were determined every 48
      h for 144 h in cellular supernatants and C3 mRNA was amplified using RT-PCR. TNF
      increased C3 release from HUVEC in a concentration dependent manner. PTX added at
      the same time as TNF significantly reduced C3 release at the 96 h time point.
      Consistent with data on C3 release PTX inhibited the increased C3 mRNA expression
      associated with TNF treatment. TNF increases C3 synthesis and release from
      endothelial cells which were inhibited by clinical concentrations of PTX. This
      data further supports the potential benefit of PTX in multiple organ dysfunction
      and other inflammatory processes involving the endothelium by inhibiting one of
      the major mediators of vascular damage.

PMID- 15467218
TI  - Effect of Sho-hange-ka-bukuryo-to on gastrointestinal peptide concentrations in
      the plasma of healthy human subjects.
AB  - Sho-hange-ka-bukuryou-to, a traditional Chinese herbal (Kampo) medicine, has been
      used to treat hyperemesis of pregnancy, nausea and vomiting. Most traditional
      herbal medicines are prepared from several herbs. For example, Sho-hange-ka
      bukuryo-to is prepared from three herbs: Pinelliae Tuber, Zingiberis Rhizoma and
      Hoelen. Thus, to determine the precise mechanism of the pharmacological effects
      of Chinese herbal medicines is too difficult. So we have elucidated the effect of
      some Chinese herbal medicines by examining the change of the plasma levels of
      brain-gut peptides. In this study, we investigated the effects of Sho-hange-ka
      bukuryo-to on the plasma levels of gut-regulated peptides (gastrin, somatostatin,
      motilin and vasoactive intestinal peptide (VIP)) and gastrointestinal mucosa
      regulatory neuropeptides (calcitonin gene-related peptide (CGRP) and substance P)
      in healthy human subjects. A single oral administration of Sho-hange-ka-bukuryo
      to caused significant increases in plasma somatostatin-, CGRP- and substance P
      immunoreactive substance (IS) levels, compared with a placebo group. Transient
      elevation of gastrin-IS levels in the placebo group was inhibited by the
      administration of Sho-hange-ka-bukuryo-to, but the medicine showed no effects on
      plasma motilin- or VIP-IS levels. In conclusion, these results might indicate
      that the pharmacological action of Sho-hange-ka-bukuryo-to is closely related to
      changes in gastrin-, somatostatin-, CGRP- and substance P-IS levels in human
      plasma.

PMID- 15467219
TI  - Comparison of the effects of Sho-hange-ka-bukuryo-to and Nichin-to on human
      plasma adrenocorticotropic hormone and cortisol levels with continual stress
      exposure.
AB  - Sho-hange-ka-bukuryo-to and Nichin-to, traditional Chinese herbal (Kampo)
      medicines have been used to treat vomiting and nausea. Traditional herbal
      medicines have frequently been used in the empirical treatment. Some patients who
      take these medicines have no organic disease but have conditions classified as
      non-ulcer dyspepsia (NUD). To determine the pharmacological effects of Sho-hange
      ka-bukuryo-to, Nichin-to, and the two herbs (Pinelliae Tuber and Zingiberis
      Rhizoma, both of which are included in Sho-hange-ka-bukuryo-to and Nichin-to), we
      examined the effects of these medicines on the plasma levels of
      adrencorticotropic hormone (ACTH) and cortisol under stress conditions by
      repetitive blood sampling. After a single administration of Kampo medicine or a
      placebo, venous blood samples were taken before and 20-240 min after
      administration. A single administration of Sho-hange-ka-bukuryo-to caused
      significant suppression of an increase in plasma ACTH-immunoreactive substance
      (IS) levels at 120 to 180 min and tended to suppress increases in plasma cortisol
      levels at 240 min, compared with the response to a placebo. A single
      administration of Nichin-to caused significant suppression of increases in plasma
      ACTH-IS levels at 120 min compared with a placebo group, but had no effect on
      plasma cortisol levels. Pinelliae Tuber had no significant effects in plasma ACTH
      IS or cortisol, but Zingiberis Rhizoma significantly suppressed the increase of
      ACTH-IS (120 min) and cortisol (180 min). These medicines have a modulatory
      effect on the hypothalamo-pituitary-adrenal (HPA) axis and autonomic nervous
      function. These effects might be beneficial in stress-related disease and suggest
      that this medicine has clinical pharmacological activity.

PMID- 15467220
TI  - Synthesis, anticonvulsant and antihypertensive activities of 8-substituted
      quinoline derivatives.
AB  - A series of 8-substituted quinolines were synthesized and tested against seizures
      induced by maximal electro shock (MES), pentylenetetrazole (scMet) and
      antihypertensive activities. Neurologic deficit was evaluated by the rotarod
      test. Among the newly synthesized derivatives, several compounds with a 2
      hydroxypropyloxyquinoline moiety displayed excellent anticonvulsant and
      antihypertensive activities. Compound 20 (8-(3'-(4''-phenylpiperazino)-2'
      hydroxypropyloxy)quinoline) was potent in both series as an anticonvulsive agent.
      13 (8-(3'-piperazino)-2'-hydroxypropyloxyquinoline) and 14 (8-(3'-imidazolo)-2'
      hydroxypropyloxyquinoline) showed very good anticonvulsant activities in the
      propanol series of compound, whereas in the ethane series, 1 (8-(2'-piperazino
      ethanoxy)quinoline) and 2 (8-(2'-imidazolo-ethanoxy)quinoline) were the most
      active as anticonvulsive agents. Compounds 20 (8-(3'-(4''-phenylpiperazino)-2'
      hydroxypropyloxy)quinoline), 13 (8-(3'-piperazino)-2'-hydroxypropyloxyquinoline)
      and 19 (8-(3'-(4''-ethylpiperazino)-2'-hydroxypropyloxy)quinoline) have shown
      excellent antihypertensive activity. They have significantly antagonized the
      pressor response elicited by adrenaline. These pharmacological results suggest
      that their anticonvulsant and antihypertensive effects may be correlated to the
      presence of beta-blocking properties, and that those properties depend on the
      presence of aryloxypropanolamine.

PMID- 15467221
TI  - Effect of Saiko-ka-ryukotsu-borei-to on amylase activity in mice.
AB  - The effects of Saiko-ka-ryukotsu-borei-to (SRBT), a Chinese medicinal
      prescription, on mouse serum amylase activity were investigated in vivo. SRBT was
      found to not only dose- and/or time-dependently augment amylase activity, but
      also to increase alpha-amylase protein content and soluble starch metabolic
      activity. These results provide a rational basis for the clinical use of SRBT
      that may accompany disease therapy.

PMID- 15467222
TI  - Oriental medicinal herb, Periploca sepium, extract inhibits growth and IL-6
      production of human synovial fibroblast-like cells.
AB  - Periploca sepium (PS) has traditionally been used in oriental medicine for
      treatment of rheumatoid arthritis (RA). We investigated the aqueous extract of PS
      (PSE) in its effects on human rheumatoid arthritis-derived fibroblast-like cells.
      In cell culture studies, PSE inhibited the growth and IL-6 production of the
      cells in dose dependent manners. The extract of Glycyrrhiza glabra (GG), which
      has also been used to treat RA and chosen as a reference here, slightly inhibited
      the growth of RA cells. A study of PSE fractionation indicated that the active
      material inhibiting IL-6 production is filterable by ultrafiltration, suggesting
      that substances with low molecular weight might be involved in an inhibition of
      IL-6 production. These results support the view that PSE represents a rich source
      of growth inhibition and anti-IL 6 production.

PMID- 15467224
TI  - Liver site-specific gene transfer following the administration of naked plasmid
      DNA to the liver surface in mice.
AB  - The present study was undertaken to investigate liver site-specific gene transfer
      following the administration of naked plasmid DNA (pDNA) to the liver surface in
      mice. We examined whether genes could be delivered to the liver site specifically
      by utilizing the glass-made diffusion cell that is able to limit the contact
      dimension between the liver surface and pDNA solution administered. Gene
      expression was detected at the site of diffusion cell attachment (site 1) and was
      significantly higher than in other liver sites and tissues. Moreover, gene
      expression was also detected at deeper site from the liver surface (noncontact
      side with pDNA solution). The level of gene expression at site 1 did not change
      significantly with pDNA treatment for 10, 30, and 60 min. In conclusion, we
      demonstrated that naked pDNA administered to the liver surface in mice was taken
      up from its surface, and subsequently the protein encoded by pDNA could be
      produced site specifically.

PMID- 15467223
TI  - Effect of rabeprazole on MDR1-mediated transport of Rhodamine 123 in Caco-2 and
      Hvr100-6 cells.
AB  - The aim of our study was to investigate the effects of rabeprazole, a proton pump
      inhibitor, on MDR1 expressed on human colon carcinoma cell line, Caco-2, and MDR1
      overexpressing human cervical carcinoma cell line, HeLa cells selected by
      exposure to 100 nM vinblastine (Hvr100-6 cells). Inhibitory effects of
      rabeprazole on MDR1-mediated transport of Rhodamine123 were examined in these
      cells. A thousand micro molar rabeprazole increased Rhodamine 123 uptakes in Caco
      2 and Hvr100-6 cells by 68% and 185%, respectively. No significant effects of
      rabeprazole were observed at the concentration of 1-100 microM. Since rabeprazole
      did not show any effects on Rhodamine 123 transport via MDR1 at the plasma levels
      (approximately 1 microM), it was considered that the drug interaction with MDR1
      substrates would be minimal even though the interaction occurred in the patients
      with rabeprazole treatment.

PMID- 15467225
TI  - Determination of optimal formulation for extrusion granulation by compression
      test of wet kneaded mass.
AB  - The purpose of this study is to propose the application of a compression test to
      the determination of an optimal formulation for extrusion granulation. The
      electric current during extrusion was measured and the characteristics of the wet
      kneaded mass in the compression test were analyzed under various operating
      conditions, with different types of extruders and several formulations of kneaded
      mass. It was found that addition of a binder (HPC-L) to pharmaceutical powders
      lowered the load of a high-compressing type extruder, since the binder reduced
      the friction among the wet mass during extrusion. Also, the support stress was
      found to be proportional to the compression pressure without a binder, although
      an inflection point appeared on the support stress curve when a binder was
      present. This inflection point suggested large water retention of the wet kneaded
      mass, at which the medium of pressure was changed from a discontinuous solid
      powder to a continuous liquid, and large water retention contributed to the low
      friction of the wet mass. The friction of the wet kneaded mass and the aptitude
      of the formulation for extrusion were understood by using the compression test.
      The compression test is a very useful procedure at the first stage of a
      formulation study.

PMID- 15467226
TI  - Synthesis and anticancer activities of 5,6,7-trimethylbaicalein derivatives.
AB  - The aim of this study was to develop potential anticancer agents based on a
      naturally occurring baicalein, a flavonoid from Scatellariae radix. Cinnamic acid
      derivatives were converted to corresponding chlorides and then condensed with
      3,4,5-trimethoxyphenol in the presence of BF(3) x Et(2)O to give chalcones.
      Intramolecular cyclization of these intermediates by the actions of DMSO/I(2)
      afforded the desired trimethylbaicalein derivatives. Cell viability after
      treatment with the tested compound for 2 d was determined by a colorimetric MTT
      assay. The results indicated that most of the derivatives showed improved
      inhibition of proliferation of Hep G2 cells. Compound 9 was the most potent, in
      which the cell viability was reduced to <2% at the 25 microM level. In the case
      of Hep 3B cells, 8a, 8b and 8f showed moderate inhibition of their proliferation
      and 25 microM was required to reduce the viability to ca. 30%. On the other hand,
      prostate DU145 cells were more resistant. Most of the derivatives caused a 60%
      inhibition of DU145 cells only at a concentration of 100 microM or above.

PMID- 15467227
TI  - A comparative study of first-derivative spectrophotometry and high-performance
      liquid chromatography applied to the determination of losartan potassium in
      tablets.
AB  - Losartan, a highly effective blood pressure-lowering agent, has been widely used
      for the treatment of hypertension. A fast and reliable method for the
      determination of losartan was highly desirable to support formulation screening
      and quality control. A first-derivative UV spectroscopic method and HPLC were
      developed for the determination of losartan in the tablet dosage form. The first
      derivative spectrum recorded between 220 and 320 nm and a zero-crossing technique
      for first-derivative measurement at 232.5 nm were selected. The selectivity and
      sensitivity of the method was in desirable range. In comparison with the direct
      UV method, first-derivative UV spectroscopy has a definite trough without any
      interference from UV absorbing-excipients. This method is also fast and
      economical in comparison with the more time-consuming HPLC method regularly used
      for formulation screening and quality control and can be used routinely by any
      laboratory possessing a spectrophotometer with a derivative accessory. The linear
      concentration ranges were 2-50 microg ml(-1), (D(1)=-0.0159C-0.0056, r=0.9994,
      n=6). Between-days CV of < or =2.9%, within-day CV of < or =2.1%, and analytical
      recovery close to 98.1% show the suitability of the method for determination in
      quality control.

PMID- 15467228
TI  - Novel squalene-hopene cyclase inhibitors derived from hydroxycoumarins and
      hydroxyacetophenones.
AB  - Squalene-hopene cyclase (SHC) is a useful model enzyme for predicting molecular
      interactions with oxidosqualene cyclase (OSC). Structure--activity relationships
      were investigated for numerous coumarin-derived inhibitors of SHC, and structural
      simplifications are suggested. Both umbelliferone and 2,4-dihydroxyacetophenone
      provide convenient starting nuclei for the design of SHC inhibitors. Derivatives
      bearing an omega-epoxyfarnesyl moiety or just a plain alkyl chain showed an
      inhibitory effect on a recombinant SHC from Alicyclobacillus acidocaldarius
      expressed in Escherichia coli.

PMID- 15467229
TI  - A new dimeric carbazole alkaloid from Glycosmis stenocarpa roots.
AB  - A new dimeric pyranocarbazole alkaloid, bisisomahanine (1), was isolated from the
      roots of Glycosmis stenocarpa (DRAKE) TAN., along with two known monomeric
      carbazole alkaloids, murrayafoline-A (2) and murrayanine (3). The planar
      structure of bisisomahanine was determined to be 9,9''-dihydroxy-3,3'',8,8''
      tetramethyl-3,3''-bis-(4-methyl-3-pentenyl)-3,3'',11,11''-tetrahydro-10,10''
      (bipyrano[3,2-a]carbazole) from the combination of spectroscopic and chemical
      evidence. Bisisomahanine is the first dimeric prenylated pyranocarbazole alkaloid
      with a 1,1' type of linkage; the NMR and CD spectroscopic data indicated it to be
      a mixture of diastereomers having a dominant configuration at the axis of
      chirality. (1)H- and (13)C-NMR assignments of murrayafoline-A were made on the
      basis of 2D-experiments.

PMID- 15467230
TI  - Binding properties of adenosine deaminase interacted with theophylline.
AB  - Thermodynamic studies were carried out to evaluate the binding of theophylline on
      adenosine deaminase (ADA) in 50 mM sodium phosphate buffer pH 7.5, at 300 K,
      using isothermal titration calorimetry (ITC). A simple method for determination
      of binding isotherm in the drug--ADA interaction was applied using ITC data. ADA
      has two binding sites for theophylline, which show positive cooperativity in its
      sites. The intrinsic association equilibrium constants are 6 and 52 mM(-1) in the
      first and second binding sites, respectively. Hence, occupation of the first site
      has produced an appreciable enhancement by 8.7 of the binding affinity of the
      second site. The molar enthalpies of binding are -12.2 and -14.9 kJ/mol in the
      first and second binding sites, respectively.

PMID- 15467231
TI  - Adsorption of bile acid by chitosan-orotic acid salt and its application as an
      oral preparation.
AB  - The orotic acid (OT) salt of chitosan (CS), CS-OT, and that of a CS derivative,
      CP, were prepared, and the adsorption of primary or secondary bile acid was
      investigated. Calcium-induced alginate gel beads (Alg-Ca) containing CS-OT were
      also prepared and autoclaved, and the possibility of these beads to act as a
      vehicle for oral administration to prevent hyperlipidemia was investigated. When
      taurocholate (TCA) and glycocholate (GCA) were present together in the medium, CS
      OT adsorbed identical amounts of both bile acids. This trend was seen in all CPs,
      although the capacity to adsorb bile acid was affected by the number and/or
      structure of the amino groups in the CP. On the other hand, taurodeoxycholate, a
      secondary bile acid was preferentially adsorbed over TCA and GCA. Alg-Ca
      containing CS-OT took up bile acids in a similar manner as CS-OT irrespective of
      the water content of the gel matrix. As all elements can be taken as a food, Alg
      Ca containing CS-OT could serve as a useful dietary agent for the prevention of
      hyperlipidemia, which is a lifestyle-related disease.

PMID- 15467232
TI  - Crystal and molecular structure of an (S)-(+)-enantiomer of modafinil, a novel
      wake-promoting agent.
AB  - The (+)-enantiomer of modafinil [(RS)-2-(diphenylmethylsulfinyl)acetamide], a
      novel wake-promoting agent, was clarified to be S-configuration by X-ray crystal
      structure analysis. The crystal consists of two crystallographically independent
      conformers that are different at the torsion angles around the sulfinylacetamide
      moiety, and this results from the molecular packing requirement to form a two
      dimensional hydrogen-bonding network via neighboring amide groups in the crystal.
      The crystal structure is characterized by the formation of alternative
      hydrophobic and hydrophilic layers, which are formed among the symmetry
      translated assemblies of diphenylmethyl and sulfinylacetamide moieties,
      respectively. The spatial orientation between the diphenyl and amide groups is
      believed to be important for the activity of modafinil.

PMID- 15467233
TI  - New Diels-Alder type adducts from Morus macroura and their anti-oxidant
      activities.
AB  - Fractionation of the ethanolic extract of the stem bark of Morus macroura
      resulted in the isolation of four new Diels-Alder type adducts, named
      guangsangons K--N (1, 2, 5, 6), together with two known compounds, mulberrofuran
      G (3) and K (4). Their structures were determined on the basis of spectroscopic
      analyses and chemical methods. Furthermore, by means of (1)H-NMR variable
      temperature experiments and the Cotton curves in the circular dichroism (CD)
      spectra, the stereochemistry of four new compounds was elucidated. The isolated
      new compounds showed good activity on anti-oxidant in vitro, with the inhibitory
      rates of MDA being from 91.8 to 100.0% at concentrations of 10(-5) mol/l.

PMID- 15467234
TI  - Bioactive constituents from Chinese natural medicines. XIV. New glycosides of
      beta-carboline-type alkaloid, neolignan, and phenylpropanoid from Stellaria
      dichotoma L. var. lanceolata and their antiallergic activities.
AB  - A new beta-carboline-type alkaloidal glycoside, glucodichotomine B, four new
      neolignan glycosides, dichotomosides A, B, C, and D, and a new phenylpropanoid
      glycoside, dichotomoside E, were isolated from a Chinese natural medicine, the
      roots of Stellaria dichotoma L. var. lanceolata. The structures of the new
      glycosides were determined on the basis of chemical and physicochemical evidence.
      Among them, dichotomoside D inhibited the release of beta-hexosaminidase
      (IC(50)=64 microM) as well as tumor necrosis factor-alpha and interleukin-4
      (IC(50)=16, 34 microM) in RBL-2H3 cells. These findings suggest that
      dichotomoside D is more effective against the late-phase reactions in type I
      allergy than in the immediate phase.

PMID- 15467235
TI  - Absolute stereostructures of polypodane-type triterpenes, myrrhanol A and
      myrrhanone A, from guggul-gum resin (the resin of Balsamodendron mukul).
AB  - Two new polypodane-type triterpenes, myrrhanol A and myrrhanone A, were isolated
      from the 50% aqueous methanolic extract of guggul-gum resin [the resin of
      Balsamodendron (=Commiphora) mukul HOOK]. The structures of the new constituents,
      including their absolute configurations, were determined on the basis of chemical
      and physicochemical evidence.

PMID- 15467236
TI  - Synthesis and biological evaluation of quinuclidine derivatives incorporating
      phenothiazine moieties as squalene synthase inhibitors.
AB  - Squalene synthase inhibitors have the potential to be superior
      hypocholesterolemic agents. A series of quinuclidine derivatives incorporating
      phenothiazine systems was synthesized in order to investigate the effects of
      their structure on the inhibition of hamster liver microsomal enzyme. (+/-)-3-(10
      Methyl-10H-phenothiazin-3-ylmethoxy)quinuclidine hydrochloride (19) was the most
      potent inhibitor in this series with an IC(50) value of 0.12 microM. Oral dosing
      of compound 19 to hamsters demonstrated effective reduction of both plasma total
      cholesterol levels and plasma triglyceride levels. Compound 19 showed a reduced
      tendency to elevate plasma transaminase levels, an indicator of hepatotoxicity.
      Enantiomerically pure (-)-19, YM-53546, was found to be more potent than the
      corresponding (+)-enantiomer.

PMID- 15467237
TI  - Studies on the constituents of Swertia japonica MAKINO I. On the structures of
      new secoiridoid diglycosides.
AB  - Eight new secoiridoid diglycosides, 6'-O-alpha-L-arabinopyranosylswertiamarin
      (1), 3'-O-beta-D-glucopyranosylswertiamarin (2), 4'-O-beta-D
      glucopyranosylswertiamarin (3), 3'-O-beta-D-galactopyranosylswertiamarin (4), 6'
      O-alpha-D-galactopyranosylswertiamarin (5), 6'-O-alpha-D
      mannopyranosylswertiamarin (6), 6'-O-beta-D-fructofuranosylswertiamarin (7) and
      5''-O-beta-D-glucopyranosylamaroswerin (12), were isolated, together with five
      known compounds from the whole plants of Swertia japonica MAKINO. The structures
      of the new compounds were elucidated on the basis of chemical and spectroscopic
      evidence. Compounds 6 and 7 are the first naturally occuring iridoid diglycosides
      having an alpha-D-mannopyranosyl unit and beta-D-fructofuranosyl unit,
      respectively.

PMID- 15467238
TI  - Sesquiterpene coumarins from Ferula fukanensis and nitric oxide production
      inhibitory effects.
AB  - Four new sesquiterpene coumarin derivatives, fukanemarin B (1), fukanefuromarin E
      (2), fukanefuromarin F (3) and fukanefuromarin G (5) were isolated from a 80%
      aqueous methanol extract of the roots of Ferula fukanensis. The structures were
      elucidated based on spectral evidence, especially heteronuclear multiple-bond
      connectivity (HMBC) and high-resolution MS. The 80% aqueous methanol extract of
      the roots of Ferula fukanensis (FFE) and the sesquiterpene coumarin derivatives
      inhibited nitric oxide (NO) production and inducible NO synthase (iNOS) gene
      expression by a murine macrophage-like cell line (RAW 264.7), which was activated
      by lipopolysaccharide (LPS) and recombinant mouse interferon-gamma (IFN-gamma).

PMID- 15467239
TI  - Surface tension calculation of mixed solvents with respect to solvent composition
      and temperature by using Jouyban-Acree model.
AB  - Applicability of a solution model, i.e. Jouyban-Acree model (JAM), for
      calculating surface tension of binary and ternary solvents at various
      temperatures has been shown employing experimental surface tension data collected
      from the literature. The accuracy of the model was evaluated by calculating
      average percentage deviation (APD) between calculated and observed values. The
      obtained overall APD (+/-S.D.) for JAM using binary solvent data were 4.06 (+/
      4.27) and 8.07 (+/-9.78)%, respectively for correlative and predictive analyses.
      The corresponding values for the best similar model from the literature were 8.86
      (+/-6.40) and 37.10 (+/-27.65)% and the mean APD differences between JAM and
      previously published model were significant (p<0.003). The capability of JAM for
      correlating surface tension of ternary solvents at various temperatures was also
      shown and the overall APD was 1.39 (+/-0.37)%.

PMID- 15467240
TI  - Development of a simple system for dehydrocondensation using solid-phase
      adsorption of a water-soluble dehydrocondensing reagent (DMT-MM).
AB  - It has been indicated that hydrophilic solid powder to which aqueous solution of
      a novel dehydrocondensing reagent DMT-MM is adsorbed becomes a simple solid-phase
      dehydrocondensing reagent of low cost. Reaction in a liquid--liquid biphasic
      system on the surface of a solid phase with a large area was accelerated by
      suspending this powder in a dichloromethane solution of a carboxylic acid and an
      amine to be condensed. The reaction was rapid with a high yield despite the
      heterogeneity of the system. Like general solid-phase reagents, a hydrophobic
      carboxamide alone could be isolated at a relatively high purity only by
      filtration of the resulting suspension of reaction mixture.

PMID- 15467241
TI  - New neolignans from Spiraea formosana.
AB  - Phytochemical investigation on the ethanol extract from the stems of Spiraea
      formosana has resulted in the isolation of four new neolignans, named spiraformin
      A, -B, -C and -D (1-4), together with thirty five known compounds. Their
      structures were established primarily on the basis of 1D and 2D NMR spectral and
      chemical transformation methods.

PMID- 15467242
TI  - A novel and concise synthesis of spirodienone alkaloids using hypervalent
      iodine(III) reagents.
AB  - Intramolecular oxidative coupling reaction of N-protected
      benzyltetrahydroisoquinoline derivatives using hypervalent iodine(III) reagents
      was investigated. The use of remarkable combination of phenyliodine bis
      (trifluoroacetate) (PIFA) and heteropoly acid (HPA) in wet acetonitrile smoothly
      afforded morphinandienone alkaloids, while neospirinedienone alkaloids were
      obtained in high yield under anhydrous conditions.

PMID- 15467243
TI  - A new phenanthrene glycoside and other constituents from Dioscorea opposita.
AB  - Phytochemical investigation of the rhizome of Dioscorea opposita has led to the
      isolation of a new phenanthrene glycoside, 3,4,6-trihydroxyphenanthrene-3-O-beta
      D-glucopyranoside (1), and five known compounds, soyacerebroside I (2), adenosine
      (3), beta-sitosterol (4), palmitic acid (5) and
      palmitoyloleoylphosphatidylcholine (6). Their structures were determined by
      spectroscopic methods, including 1D- and 2D-NMR. Compounds 1-6 exhibited no
      antifungal activity against the human pathogenic yeasts Candida albicans, C.
      glabrata and C. tropicalis.

PMID- 15467244
TI  - A conventional route for the synthesis of new oxazolidin-2-one derivatives with
      beta-aminoalanines.
AB  - A conventional new route to the novel oxazolidin-2-one derivatives (3a-f) having
      two substituents on N-3 and C-4 in the oxazolidin-2-one ring was established with
      racemic beta-aminoalanine derivatives (1) as the key starting materials.

PMID- 15467245
TI  - A new lignan glycoside and phenylethanoid glycosides from Strobilanthes cusia
      BREMEK.
AB  - The root of Strobilanthes cusia BREMEK. (Acanthaceae), popularly known as Da
      Ching-Yeh, has been commonly used in traditional Chinese medicine. It is used to
      treat influenza, epidemic cerebrospinal meningitis, encephalitis B, viral
      pneumonia, mumps, and severe acute respiratory syndrome (SARS). In this study, we
      found a new lignan glycoside (6) and two new phenylethanoid glycosides (7, 8)
      together with five known compounds as chemical constituents of Strobilanthes
      cusia root. Some samples were examined for anti-herpes simplex virus type-1 (HSV
      1) activity. Among the tested samples, lupeol showed anti-HSV-1 activity (EC(50):
      11.7 microM) and showed 100% inhibition of virus plaque formation at 58.7 microM.

PMID- 15467246
TI  - Antiinflammatory triterpenoid saponins from the seeds of Aesculus chinensis.
AB  - Phytochemical study of the ethanol extract of the seeds of Aesculus chinensis led
      to the isolation of a new triterpenoid saponin (6), together with five known
      triterpenoid saponins (1-5). The structure of the new compound was elucidated on
      the basis of spectral data to be 21,28-di-O-acetylprotoaescigenin-3-O-[beta-D
      glucopyranosyl(1-2)][beta-D-glucopyranosyl(1-4)]-beta-D-glucopyranosiduronic acid
      (aesculiside A, 6). The antiinflammatory activities of the four main saponins (1
      4) were compared with those of total saponin extracts, and single saponins showed
      more potent activity than total saponin extracts in mice.

PMID- 15467247
TI  - Two new monoterpene glycosides and trypanocidal terpenoids from Dracocephalum
      kotschyi.
AB  - From the whole plant of Dracocephalum kotschyi BOISS., two new monoterpene
      glycosides (9, 10), together with seven known terpenoids and a phytosterol (1-8),
      were isolated. Their structures were determined to be limonen-10-al (1), geranial
      (2), neral (3), beta-sitosterol (4), oleanolic acid (5), ursolic acid (6), p
      mentha-8-en-1,2-diol (7), colosolic acid (8), limonen-10-ol 10-O-beta-D
      glucopyranoside (9), and limonen-10-ol 10-O-beta-D-glucopyranosyl-(1-->2)-beta-D
      glucopyranoside (10). Compounds 1 (3.1 microM), 2 (3.1 microM), 3 (3.1 microM), 5
      (6.2 microM), 6 (6.2 microM), and 8 (6.2 microM) were effective against
      epimastigotes of Trypanosoma cruzi.

PMID- 15467248
TI  - Simultaneous determination of chlorogenic acid, caffeic acid, ferulic acid,
      protocatechuic acid and protocatechuic aldehyde in Chinese herbal preparation by
      RP-HPLC.
AB  - In the present study, a reversed phase high performance liquid chromatographic
      (RP-HPLC) method was established for simultaneous determination of chlorogenic
      acid, caffeic acid, ferulic acid, protocatechuic acid and protocatechuic aldehyde
      in a Chinese herbal preparation (Fufang-Pugongying-Mixture). The separation was
      performed on a Hypersil ODS-2 column by isocratic elution with methanol and 0.2 M
      acetate buffer (pH 3.6) (15 : 85, v/v) as the mobile phase at the flow-rate of
      1.0 ml/min with operating temperature of 30 degrees C, and detection wavelength
      of 300 nm. A good linear regression relationship between peak-areas and
      concentrations was obtained over the range of 2-200 microg/ml for the five marker
      compounds mentioned above. The spike recoveries were within 96.72-104.07%. The
      variation coefficient (CV) values of the precision were in the range of 0.89
      4.50%. Moreover the developed method has reference value for quantitative
      analysis of Taraxacum, Lonicera and Angelica.

PMID- 15467249
TI  - New butenolides in plantlets of Virola surinamensis (Myristicaceae).
AB  - A phytochemical investigation in plantlets of the Brazilian medicinal tree Virola
      surinamensis resulted in the isolation and structural determination of four new
      compounds: 3-hydroxy-4-methyl-2-(11'-piperonyl-n-undecyl)-butenolide; 3-hydroxy-4
      methyl-2-(7'-piperonyl-n-heptyl)-butanolide; 9'-(3,4-methylenedioxy-phenyl)
      nonanoic acid and 13'-(3,4-methylene-dioxyphenyl)-tridecanoic acid. Thirteen
      compounds previously isolated from seeds and adult plants were also reported.

PMID- 15467250
TI  - New oleanan-type triterpene and cincholic acid glycosides from Peruvian "Una de
      Gato" (Uncaria tomentosa).
AB  - A new oleanan-type triterpene and three new cincholic acid glycosides were
      isolated from Peruvian "Una de Gato" (Cat's claw, plant of origin: Uncaria
      tomentosa), a traditional herbal medicine in Peru. Their structures were
      determined by spectroscopic analysis.

PMID- 15467251
TI  - Chrysophanol glycosides from callus cultures of monocotyledonous Kniphofia spp.
      (Asphodelaceae).
AB  - We established callus cultures of the monocotyledonous plants Kniphofia foliosa
      and K. tuckii (Asphodelaceae), which produce the anthraquinone derivatives
      chrysophanol and its glycosides. The minor product chrysophanol 8-O-beta
      gentiobioside was fully characterized by spectroscopic analysis and synthesis.

PMID- 15467252
TI  - A new lignan from Balanophora abbreviata and inhibition of lipopolysaccharide
      (LPS)-induced inducible nitric oxide synthase (iNOS) expression.
AB  - Six lignans including a new lignan (1), beta-sitosterol glucopyranoside and
      phenylpropanoids were isolated from the whole plants of Balanophora abbreviata
      Bl. (Balanophoraceae). Their structures were determined by NMR, MS analysis and
      other spectroscopic methods. Lignans (1, 2 and 4) showed potent inhibitory
      activities on the lipopolysaccharide (LPS)-induced inducible nitric oxide
      synthase (iNOS) expression in RAW 264.7 cells.

PMID- 15467253
TI  - [A molecular basis for odorant recognition: olfactory receptor pharmacology].
AB  - Olfactory receptors (ORs) comprise the largest super-family of rhodopsin-like G
      protein coupled receptors (GPCR) that involve the recognition and discrimination
      of thousands of odorants. We recently succeeded in functional reconstitution of
      mouse ORs in mammalian cell lines and provided molecular evidence that
      structurally-related ORs recognized overlapping sets of odorants with distinct
      ligand specificities. Here we show that mOR-EG, a mouse olfactory receptor that
      was isolated from a eugenol-responsive cell, recognizes 22 different odorants
      with EC50 values ranging from a few microM to several hundred microM. We
      constructed a molecular model of mOR-EG using the recent atomic-level structure
      of bovine rhodopsin. Site-directed mutations were introduced in a potential
      ligand-binding pocket based on computational ligand-docking simulation. Mutations
      of some amino acid residues in TM3, TM5, and TM6 dramatically affected the EC50
      value of eugenol in Ca2+ imaging. Finally, we succeeded in rational receptor
      design with predicted ligand specificity by introducing point mutations in the
      binding site, confirming the accuracy of the binding site mapping. The current
      studies also help understand mechanisms underlying molecular recognition by
      GPCRs, with implications for therapeutic application.

PMID- 15467254
TI  - [Gut nutrient sensing by the abdominal vagus].
AB  - Gustatory and anticipatory cephalic stimuli that are detected during a meal yield
      nutritional information and aid in the efficient digestion of food. It is
      possible that animals can detect the amount of dietary food and its quality via
      cephalic relay to initiate proper digestion in the alimentary tract. The
      abdominal vagus conveys primary afferent nutritional information from the
      digestive system to the brain and modulates gastrointestinal motor and secretory
      activity that ensures the food digestion through local and central reflexes.
      Almost all the 5-HT in the body exists in the enterochromaffin (EC) cells in the
      alimentary tract, but the physiological significance of the mucosal 5-HT is not
      well elucidated. In the present paper, we reviewed recent advances in studies on
      gut nutrient perception and proposed the hypothesis that 5-HT derived from EC
      cells acts as a general transmitter of gut nutrient sensing by the abdominal
      vagus.

PMID- 15467255
TI  - [Molecular mechanisms of thermosensation].
AB  - We feel a wide range of temperatures spanning from cold to heat. Within this
      range, temperatures over about 43 degrees C and below about 15 degrees C evoke
      not only a thermal sensation, but also a feeling of pain. In mammals, six
      thermosensitive ion channels have been reported, all of which belong to the TRP
      (transient receptor potential) super family. These include TRPV1 (VR1), TRPV2
      (VRL-1), TRPV3, TRPV4, TRPM8 (CMR1), and TRPA1 (ANKTM1). These channels exhibit
      distinct thermal activation thresholds (>43 degrees C for TRPV1, >52 degrees C
      for TRPV2, >32-39 degrees C for TRPV3, >27-35 degrees C for TRPV4, <25-28 degrees
      C for TRPM8, and <17 degrees C for TRPA1) and are expressed in primary sensory
      neurons as well as other tissues. The involvement of TRPV1 in thermal nociception
      has been demonstrated by multiple methods, including the analysis of TRPV1
      deficient mice. Temperature thresholds for activation of TRPV1, TRPV4, and TRPM8
      are not fixed but changeable. Reduction of the temperature threshold for TRPV1
      activation is thought to be one mechanism of inflammatory pain. Significant
      advances in thermosensation research have been made in the last several years
      with the cloning and characterization of thermosensitive TRP channels. With these
      clones in hand, we can begin to understand thermosensation from a molecular
      standpoint.

PMID- 15467256
TI  - [ATP receptors in pain sensation].
AB  - We reported that activation of P2X2/3 heteromeric channels in A delta-DRG neurons
      causes tactile allodynia and activation of P2X3 in C-fiber causes nocifensive
      behavior. We also found that tactile allodynia under the chronic pain state
      requires an activation of P2X4 ionotropic ATP receptor and p38 mitogen-activated
      protein kinase in spinal microglia.

PMID- 15467257
TI  - [Heterogeneity of G protein-coupled receptor generated by post-translational
      mechanisms and its clinical meanings].
AB  - G protein-coupled receptors (GPCRs) are the most famous target proteins for
      medicinal drugs. So far, heterogeneity of GPCRs is mainly focused on genetic
      variation. However, it has been reported that the structure and function of GPCRs
      are modified by several mechanisms after translation. RNA editing introduces the
      amino acid different from that encoded in genome by changing the nucleotide.
      Dimer formation is another example of how heterogeneity is produced. Many
      receptors form homo- or hetero-dimers, and obtain different function from
      original receptors. Receptors are regulated by several means to modulate
      stimulation strength. Receptor subtype is often differentially regulated by
      receptor kinases and/or second messenger-regulated kinases. There is a new type
      of receptor that shows a novel structural feature, a long amino terminal region
      belonging to class B seven transmembrane receptors. The physiological function of
      this class of receptor is assumed to play a role in cell-cell communication. This
      novel structural feature may directly link GPCR to the cytoskeleton. These
      mechanisms to produce functional and structural heterogeneity may explain how
      cells evoke different responses in different tissues or cells upon the same
      stimulation. Thus, the post-translational mechanism to produce heterogeneity
      provides additional flexibility when cells respond to one extracellular stimulus.

PMID- 15467258
TI  - [Pharmacological and clinical profile of mitiglinide calcium hydrate (Glufast), a
      new insulinotropic agent with rapid onset].
AB  - Mitiglinide calcium hydrate (mitiglinide, Glufast) is a new insulinotropic agent
      of the glinide class with rapid onset. Mitiglinide is thought to stimulate
      insulin secretion by closing the ATP-sensitive K(+) (K(ATP)) channels in
      pancreatic beta-cells, and its early insulin release and short duration of action
      would be effective in improving postprandial hyperglycemia. In studies of various
      cloned K(ATP) channels, mitiglinide shows a higher selectivity for the beta-cell
      type of SUR1/Kir6.2 than the cardiac and smooth muscle types of K(ATP) channels
      in comparison with glibenclamide and glimepiride. In vitro and in vivo studies
      demonstrated the insulinotropic effect of mitiglinide is more potent than that of
      nateglinide, and mitiglinide surpassed in controlling postprandial hyperglycemia
      in normal and diabetic animals. In clinical trials, treatment with mitiglinide
      provided lasting improvement of postprandial hyperglycemia in Type 2 diabetic
      patients and decreased the fasting plasma glucose levels and HbA(1C) values. The
      incidence of adverse events related to mitiglinide were nearly equivalent to
      placebo; in particular there was no difference with the frequency of
      hypoglycemia. The results from these studies indicated that mitiglinide could be
      expected to possess good therapeutic features of being effective in reducing
      postprandial glucose excursions in the early stage of Type 2 diabetes and less
      incidence of events suggestive of hypoglycemia.

PMID- 15467259
TI  - [Pharmacological profiles and clinical effects of olmesartan medoxomil, a novel
      angiotensin II receptor blocker].
AB  - Olmesartan medoxomil is a new angiotensin II receptor blocker (ARB) indicated for
      the treatment of hypertension. Olmesartan medoxomil is a pro-drug that is
      converted to the active metabolite olmesartan. Olmesartan does not undergo
      further metabolism and does not interact with cytochrome P450 enzymes. Olmesartan
      is a potent ARB with high selectivity for the type 1 (AT(1)) receptor subtype and
      shows insurmountable antagonism against the AT(1) receptor in vascular tissues.
      This antagonistic mode, which could be attributed to tight binding of this drug
      to the receptor, would underlie the potent and persistent action of olmesartan
      medoxomil in vivo. In fact, oral administration of olmesartan medoxomil produces
      a potent and long-lasting antihypertensive action without inducing tachycardia.
      The preventive effects of olmesartan medoxomil on end-organ damage in the kidney,
      heart, and blood vessels have been demonstrated in various animal models. In
      clinical studies, olmesartan medoxomil is shown to be well tolerated and have an
      excellent safety profile that is comparable to that of placebo. Head-to-head
      comparisons with other ARBs (losartan, valsartan, irbesartan, and candesartan
      cilexetil) conducted in the United States and Europe have revealed that
      olmesartan medoxomil is superior to these other ARBs in lowering blood pressure.
      These facts suggest that olmesartan medoxomil would be beneficial for the
      treatment of hypertension and other end-organ diseases.

PMID- 15467260
TI  - [Anti-allergic action effect of Pseudolarix amabilis Rehd. extract and its
      efficacy on atopic dermatitis].
AB  - Pseudolarix amabilis Rehd. extract was examined in vitro for antibacterial
      effects, anti-inflammatory effects, and inhibitory effects on histamine release.
      Pseudolarix amabilis Rehd. extract was also examined for efficacy on dermatitis
      in atopic dermatitis model mice (NC mice) and effects on keratinous moisture
      level and transepidermal water loss in miniature pigs. Pseudolarix amabilis Rehd.
      extract had antibacterial effects on Staphylococcus aureus, Candida albicans, and
      Streptococcus pyogenes; however this antibacterial effect varied with the
      temperature at which and conditions under which Pseudolarix amabilis Rehd. was
      extracted. Pseudolarix amabilis Rehd. extract at the final concentration of 2
      mg/mL significantly inhibited the hyaluronidase activity; and at 0.005, 0.05, and
      0.5 mg/mL, it also significantly inhibited the histamine release. In the mice in
      which atopic dermatitis had been induced, 28-day administration of Pseudolarix
      amabilis Rehd. extract at 4 and 400 mg/mL significantly inhibited aggravation of
      dermatitis without having effects on body weight. In the dorsal skin of miniature
      pigs, Pseudolarix amabilis Rehd. extract at 4 and 400 mg/mL significantly
      increased keratinous moisture level with the increase in the number of dosing
      days, and caused no changes in transepidermal water loss. From the above results,
      it is clear that Pseudolarix amabilis Rehd. extract inhibits both proliferation
      of bacteria and inflammation caused by antigens. Furthermore, it is suggested
      that Pseudolarix amabilis Rehd. extract will serve as a medicinal drug which
      effectively moistens the skin and prevents and heals dermatitis.

PMID- 15467261
TI  - Prior antagonism of endothelin-1A receptors alleviates circulatory shock and
      cerebral ischemia during rat heatstroke.
AB  - In this study, we investigated the acute hemodynamic effects of an infusion of
      the endothelin-1 (ET-1)-A-selective receptor antagonists BQ-610 and BQ-123 in
      heatstroke rats with circulatory shock and cerebral ischemia. Heatstroke was
      induced by putting the anesthetized adult Sprague-Dawley rats into an ambient
      temperature of 42 degrees C. The moment in which the mean arterial pressure
      dropped irreversibly from the peak for an extent of 25 mmHg was taken as the
      onset of heatstroke. The interval between initiation of heat exposure and
      heatstroke onset was found to be about 80 min for rats treated with vehicle
      solution. When the animals were exposed to 42 degrees C for 80 min, hyperthermia,
      arterial hypotension, decrement of cardiac output (due to decreased stroke volume
      and decreased total peripheral resistance), increment of plasma ET-1 and tumor
      necrosis factor-alpha, and increment of cerebral ischemia and injury markers were
      manifested. Prior antagonism of ET-1 A receptors with BQ-610 (0.5 mg/kg, i.v.) or
      BQ-123 (1 mg/kg, i.v.), but not ET-1B receptors with BQ-788 (0.5 mg/kg, i.v.), 60
      min before the initiation of heat exposure, appreciably alleviated hyperthermia,
      arterial hypotension, decreased cardiac output, increment of tumor necrosis
      factor-alpha, and increment of cerebral ischemia (e.g., glutamate and
      lactate/pyruvate ratio) and injury (e.g., glycerol) markers exhibited during
      heatstroke. The data indicates that ET-1A receptor antagonism may maintain
      appropriate levels of mean arterial pressure and cerebral circulation during
      heatstroke by reducing production of tumor necrosis factor-alpha.

PMID- 15467262
TI  - Role of corticotropin-releasing factor receptor type 2 beta in urocortin-induced
      vasodilation of rat aortas.
AB  - Urocortin has a high affinity for the corticotropin-releasing factor receptor
      type 2beta (CRF-R2beta). This study was conducted to reveal the role of CRF
      R2beta in blood vessels. CRF-R2beta expressions were detected both in smooth
      muscle and endothelium from Wistar Kyoto rats (WKY) and spontaneously
      hypertensive rats (SHR) aortas, and there was no significant difference between
      them. Urocortin reduced phenylephrine-induced contraction of aorta with
      endothelium dose-dependently in both rats. However, deendothelialization
      significantly but not completely (about 50%) reduced the vasodilation. The
      reduction of vasodilatory action of urocortin by deendothelialization was age
      dependent in SHR. An adenylyl cyclase inhibitor, SQ22536, significantly inhibited
      urocortin-induced relaxation in denuded WKY and SHR aortas, while in preparations
      with endothelium, neither SQ22536 nor L-NMMA reduced the relaxation. However,
      simultaneous addition of both drugs significantly reduced the relaxation. In
      contrast to young rats (7-week-old), in aged rats (19-week-old), L-NMMA
      successfully reduced urocortin-induced relaxation of aorta with endothelium.
      These results suggest that urocortin relaxes aorta at least partly via two signal
      pathways, that is, an increase in intracellular cAMP by binding to CRF-R2beta
      expressed in smooth muscle cells and NO production from endothelium evoked by
      binding to the receptors expressed in endothelium and that aging increases the
      role of the latter system.

PMID- 15467263
TI  - Effect of a selective inhibitor of secretory phospholipase A2, S-5920/LY315920Na,
      on experimental acute pancreatitis in rats.
AB  - We investigated the efficacy of a potent inhibitor of secretory phospholipase A2
      (sPLA2), S-5920/LY315920Na, in an experimental model of acute pancreatitis in
      rats. Combined intraductal injection of sodium taurocholate (5 mg/rat) and
      porcine pancreatic sPLA2-IB (300 microg/rat) caused severe hemorrhagic
      necrotizing pancreatitis resulting in high mortality, along with rapid increases
      of catalytic PLA2 and lipase activities in plasma and ascites and with gradual
      increases of plasma amylase and aspartate aminotransferase levels over 9 h after
      the pancreatitis. Prophylactic intravenous treatment with S-5920/LY315920Na
      significantly reduced mortality at 7 days, and strongly abrogated PLA2 activities
      in both plasma and ascites along with significant reduction of lipase activity,
      amylase, aspartate aminotransferase, and hemorrhage at 6 h. It also significantly
      reduced histological damage such as edema and parenchymal and fat necroses of the
      pancreatic tissue. This sPLA2 inhibitor could become an effective agent for the
      treatment of severe acute pancreatitis.

PMID- 15467264
TI  - Tetrahydrobiopterin uptake in supplemental administration: elevation of tissue
      tetrahydrobiopterin in mice following uptake of the exogenously oxidized product
      7,8-dihydrobiopterin and subsequent reduction by an anti-folate-sensitive
      process.
AB  - In order to increase the tissue level of tetrahydrobiopterin (BH4),
      supplementation with 6R-tetrahydrobiopterin (6RBH4) has been widely employed. In
      this work, the effectiveness of 6RBH4 was compared with 7,8-dihydrobiopterin
      (7,8BH2) and sepiapterin by administration to mice. Administration of 6RBH4 was
      the least effective in elevating tissue BH4 levels in mice while sepiapterin was
      the best. In all three cases, a dihydrobiopterin surge appeared in the blood. The
      appearance of the dihydrobiopterin surge after BH4 treatment suggested that
      systemic oxidation of the administered BH4 had occurred before accumulation of
      BH4 in the tissues. This idea was supported by the following evidences: 1) An
      increase in tissue BH4 was effectively inhibited by methotrexate, an inhibitor of
      dihydrofolate reductase which reduces 7,8BH2 to BH4. 2) When the unnatural
      diastereomer 6SBH4 was administered to mice, a large proportion of the recovered
      BH4 was in the form of the 6R-diastereomer, suggesting that this BH4 was the
      product of a dihydrofolate reductase process by which 7,8BH2 converts to 6RBH4.
      These results indicated that the exogenous BH4 was oxidized and the resultant
      7,8BH2 circulated through the tissues, and then it was incorporated by various
      other tissues and organs through a pathway shared by the exogenous sepiapterin
      and 7,8BH2 in their uptake. It was demonstrated that maintaining endogenous
      tetrahydrobiopterin in tissues under ordinary conditions was also largely
      dependent on an methotrexate-sensitive process, suggesting that cellular
      tetrahydrobiopterin was maintained both by de novo synthesis and by salvage of
      extracellular dihydrobiopterin.

PMID- 15467265
TI  - Alternative splicing of human telomerase reverse transcriptase may not be
      involved in telomerase regulation during all-trans-retinoic acid-induced HL-60
      cell differentiation.
AB  - Alternative splicing of the human telomerase reverse transcriptase subunit
      (hTERT) suppresses telomerase activity during the development of human fetal
      kidney cells into mature cells. Tumor cell differentiation is the process of
      turning abnormal tumor cells into 'normal' cells accompanied by down-regulation
      of telomerase activity. However, the precise mechanism of the regulation of
      telomerase activity in differentiated cells is not fully understood. In this
      study, we observed the role of alternative splicing of hTERT in the regulation of
      telomerase activity in all-trans-retinoic acid (ATRA)-induced, differentiated HL
      60 cells. ATRA-induced down-regulation of telomerase activity in differentiated
      HL-60 cells was associated with a decrease in hTERT and an increase in human
      telomerase-associated protein-1 (hTP1) transcription. Expression of full length
      variant hTERT alpha+ beta+ mRNA decreased in a dose- and time-dependent manner.
      The drop of hTERT beta- mRNA was time-dependent. hTERT alpha- and hTERT alpha-
      beta- mRNA were reduced dramatically after ATRA treatment. In the dose-effect
      study, hTERT alpha+ beta+ and hTERT beta- maintained a relatively stable ratio
      when telomerase activity decreased largely from treatment with 1 to 5 microM
      ATRA. Although the splicing pattern of hTERT mRNA was altered in time-effect
      research, the change was not related to the ATRA-treated decline of telomerase
      activity. The expression of alternative splicing variants of hTERT also decreased
      at the protein level. All these results suggested that alternative splicing of
      hTERT mRNA may not contribute to the suppression of telomerase activity during
      ATRA-induced HL-60 leukemia cell differentiation.

PMID- 15467266
TI  - Function of sexual glands and mechanism of sex differentiation.
AB  - Prior to any investigation of toxicant effects on sexual development it is
      necessary to have a complete understanding of the relevant physiology of
      reproductive development. Beginning at conception, development of males and
      females diverge to form the respective reproductive systems. From the prenatal
      period to the interval following puberty, radical changes take place in the
      hypothalamo-pituitary-gonadal axis of males and females. The complexity of each
      of these systems and their development is mirrored in the many possibilities for
      the means by which chemicals may produce adverse effects. For example, a chemical
      that affects hormone synthesis may, if administered at the proper time, affect
      hypothalamic development. As a consequence, pubertal development may not occur
      normally. In this chapter, we have outlined the basics of reproductive
      development and provided examples of adverse effects by endocrine disrupting
      chemicals (EDCs) on such development.

PMID- 15467267
TI  - Quantitative estimation of myocardial fibrosis based on receptor occupancy for
      beta2-adrenergic receptor agonists in rats.
AB  - To develop beta2-adrenergic receptor (AR) agonists with higher selectivity, it is
      essential to evaluate the cardiac side effects which are the most serious side
      effects of this class of drugs. We studied receptor occupancy of beta1-ARs in
      rats as a possible cause for the side effect of beta2-AR agonists, namely
      myocardial fibrosis. Myocardial fibrosis in rats was observed on Day 7 after the
      administration of salbutamol and terbutaline, both of which are selective beta2
      AR agonists, at higher dose levels. To evaluate receptor occupancy, plasma
      concentrations of (R)-salbutamol and (R)-terbutaline, plasma protein binding and
      the EC50 for chronotropic effects in rats were determined. Based on the plasma
      concentrations, the plasma protein binding and EC50, receptor occupancy-time
      profiles were constructed. The relationship between the receptor occupancy-time
      profile under the curve, the AUCphi, and the degree of myocardial fibrosis was
      evaluated with a multiple correlation analysis. Myocardial fibrosis was
      significantly correlated (r2 > 0.78) to the AUCphi with the threshold above
      approximately 50%, but not to plasma concentrations. These results indicate that
      the receptor occupancy theory is also useful for the evaluation of the
      chronotropic side effects of beta2-AR agonists.

PMID- 15467268
TI  - The effect of testosterone propionate supplement on testicular toxicity with
      thiamphenicol in male Sprague-Dawley rats.
AB  - Testosterone propionate (TP) was supplemented to male rats for assessment of its
      ameliorating effect on testicular toxicity with thiamphenicol (TAP). A total of
      20 male Sprague-Dawley rats were treated orally with TAP at 200 mg/kg/day for up
      to 4 weeks. In addition, 5 male rats were allotted to the control group receiving
      vehicle only. Ten of the 20 treated rats had a Silastic capsule (containing about
      80 mg of TP) implanted in the dorsal skin at Week 2 and assigned to the TAP-TP
      group, while the other 10 treated rats were in the TAP group. After Weeks 3 and
      4, five of both treated groups were examined for weight and histology of the
      testis and accessory genital glands, and for staging analysis of the seminiferous
      tubules. The same parameters were also assessed in the control group after Week
      4. Weights and morphology of the seminal vesicle and prostate recovered
      remarkably from the TAP toxicity after TP supplement. However, no ameliorating
      effects of TP were obtained for the testis in either weight, morphology, or
      staging analysis of the seminiferous tubules.

PMID- 15467269
TI  - Altered tissue concentration of minerals in spontaneous diabetic rats (Goto
      Kakizaki rats).
AB  - A relationship has been reported between trace elements and diabetes mellitus.
      This study examined the concentration of several trace elements (Zn, Mg, Ca, Fe,
      Cu, Mn, P) in each organ from spontaneous type 2 diabetic model rat (GK rat) and
      compared with control. Results showed that diabetic rat excreted 1.25-, 1.5-fold
      more zinc and magnesium, respectively, than control in the urine. Contents of
      zinc and magnesium in kidney and testis and fatty tissue were lowered
      significantly in GK rat. Zinc in liver and magnesium in lung were also lowered.
      Concentrations of other trace elements also changed in some organs from GK rats
      compared with those from control. These results demonstrate that trace element
      imbalances come out significantly in mild diabetes and the need to instruct a
      nutritionally balanced diet that takes account of trace elements in diabetes from
      the early stage.

PMID- 15467270
TI  - Impact of globalization under the ICH guidelines on the conduct of reproductive
      toxicity studies--report on current status in Japan, Europe and the U.S. by
      questionnaire survey.
AB  - We surveyed interpretation of the ICH guidelines concerning reproductive
      toxicology. Valid responses were obtained from Japan (JPN), Europe (EUR) and the
      U.S. The results obtained were compared to those at the time of a previous survey
      targeted at JPN facilities in 1995-1996 as well as compared among all three
      regions. Compared to the previous survey in Japan, the number of facilities
      performing toxicokinetics (TK) in rats has slightly increased. This result was
      considered to represent changes of attitude toward TK in reproductive toxicity
      studies. Differences in interpretation of the guidelines between JPN, EUR and the
      US were widely seen. Clear differences were noted in sperm examinations,
      postnatal tests, fetal examinations, some examinations for F1 animals after
      culling and TK. Researchers in the West seemed to be interpreting the ICH
      guidelines more flexibly from the scientific point of view. JPN researchers
      appeared to interpret the guidelines, including notes, as rigid requirements.
      Most of the parts which produced different interpretations were the notes in the
      guidelines. The force of mention in the notes should be defined in the future. In
      addition, there were doubts about some parts, including notes, which had been
      found to have become unsuitable for the implementation of studies because of
      scientific progress or from long experience in using the guidelines. Therefore,
      updates of the guidelines may be needed in the future as well as the remedy of
      interpretation by JPN researchers. In JPN, the number of reproductive toxicity
      studies has decreased. The scanty experience in JPN therefore raises apprehension
      of appropriate selection and stagnating development of methodology, and might
      hinder the maintenance of the guidelines. In the future, the cooperation of CROs
      as well as global collaboration will be essential not only to scientific
      developments of reproductive toxicology but also updates of the guidelines.

PMID- 15467271
TI  - Key parameters of sperm motion in relation to male fertility in rats given alpha
      chlorohydrin or nitrobenzene.
AB  - This study was undertaken to detect key parameters of rat sperm motion in
      relation to male fertility by comparing the differences in sperm motion induced
      by treatment with alpha-chlorohydrin (ACH), known to produce spermatotoxicity,
      and nitrobenzene (NTB), known to produce testicular toxicity. Male rats received
      ACH (5 or 20 mg/kg/day) or NTB (60 mg/kg/day) for either 3 days or 18 days.
      Epididymal sperm was assessed for motility using a Hamilton-Thorne Sperm Analyzer
      (HTM-IVOS). Numerical data for statistical analysis and graphical renditions of
      sperm motion using parameters in radar charts and reconstructed sperm tracks were
      analyzed to evaluate sperm motion. Males were allowed to copulate with untreated
      females and cesarean sections were conducted in order to examine the effects of
      drug administration on male fertility. Linearity of sperm track (linearity (LIN)
      and/or straightness (STR)) decreased and/or beat cross frequency (BCF) increased
      only in ACH groups (5 or 20 mg/kg/day), although the percentage of motile sperm,
      sperm velocities (average path velocity (VAP), curvilinear (VCL), and straight
      line velocity (VSL)) and amplitude of lateral head displacement (ALH) decreased
      on Day 18 in both ACH and NTB (60 mg/kg/day) groups. Furthermore, from the
      individual reconstructed sperm tracks, it was clear that ACH-treated spermatozoa
      were characterized by abnormal motion ("jerking") with low vigor (low velocities)
      and little or no forward progression. Finally, only ACH treatment led to a
      reduction in pregnancy rate or infertility. Therefore, our results suggest that
      linearity (especially VSL, STR and LIN) in sperm motion is a key parameter for
      assessing a chemical's potential to induce male infertility.

PMID- 15467272
TI  - [Dehydrative glycosidation and partially benzylated sugar derivatives].
AB  - Dehydrative glycosidation reactions reported by the authors' group are reviewed.
      The authors' efforts were concentrated on developing reagent systems usable for
      one-stage-one-pot glycosidation. Such systems could simplify the glycosidation
      step using 1-OH sugar derivatives, since any preactivation stage for the
      hemiacetal OH group could be omitted. The systems, utilizing the dehydration
      potential of sulfonyl chloride, such as the p-nitrobenzenesulfonyl chloride
      silver trifluoromethanesulfonate-triethylamine system as well as the p
      nitrobenzenesulfonyl chloride-silver trifluoromethanesulfonate-N,N
      dimethylacetamide-triethylamine system, were useful for the syntheses of many
      kinds of oligosaccharides. As a system free from any metals, the authors
      developed the trimethylsilyl trifluoromethanesulfonate-pyridine (TP) system.
      During the study of the system containing cobalt (II) bromide, the authors found
      that the bromide converts 1-OH sugar into the corresponding 1-Br derivative,
      which is then activated with the cobalt salt to undergo glycosidation with
      alcohol. To prepare partially benzylated sugar derivatives used as acceptors in
      the authors' studies, controlled benzylation and forced tritylation were carried
      out. Short syntheses of a variety of useful sugar derivatives using such
      convenient procedures are described. As a novel protecting group for the
      hemiacetal OH group, the authors used the 2-methoxyethyl group. Many kinds of
      trehalose-type disaccarides we prepared.

PMID- 15467273
TI  - [Defense of living body against oxidative damage].
AB  - Living bodies may experience oxidative stress induced by reactive oxygen species
      and heavy metal ions, which may damage components in the body and cause aging and
      disorders. In addition to the known defense systems against oxidative damage, the
      author describes new defense systems. Lipid peroxidation in living bodies, which
      has hitherto been thought to increase oxidative damage, was found to attenuate
      oxidative stress-induced DNA damage. Red blood cells become senescent due to
      oxidative stress during circulation, where membrane band 3 becomes aggregated to
      anti-band 3 IgG and macrophages attached through poly-N-acetyllactosaminyl sugar
      chains, and the sugar chain attachment to macrophages is stimulated by oxidative
      stress in macrophages. Oxidized protein hydrolase that preferentially hydrolyzes
      proteins damaged by oxidative stress was newly discovered, which may play an
      important role in saving cells from oxidative damage.

PMID- 15467274
TI  - [Mice lacking PACAP: a mini-review focussing on brain function].
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the
      vasoactive intestinal peptide (VIP)/ secretin/ glucagon superfamily and functions
      as a hormone, neurohormone, and neurotransmitter in the central nervous system as
      well as in several peripheral tissues. Recently, several groups including ours
      have independently produced lines of mice lacking PACAP (PACAP(-/-)). These
      mutant mice have not only led to a better understanding of the physiologic roles
      of endogenous PACAP, but have also revealed some unexpected roles of PACAP. In
      this paper, phenotypic changes in several brain functions in PACAP(-/-) mice,
      including light-induced phase-resetting of the circadian activity rhythm,
      hippocampal long-term potentiation, and psychomotor behaviors, are reviewed based
      on the results obtained in our laboratory.

PMID- 15467275
TI  - [Systematic synthesis of antitumor annonaceous acetogenins].
AB  - Systematic synthesis of mono- and bis-THF ring cores, synthetic intermediates of
      antitumor annonaceous acetogenins, has been achieved by asymmetric alkynylation
      and subsequent stereodivergent THF ring formation as key steps. The asymmetric
      alkynylation of alpha-oxyaldehyde and alpha-tetrahydrofuranic aldehyde with (S)-3
      butyne-1,2-diol derivatives gave good yield with very high diastereoselectivity.
      These adducts were converted into mono- and bis-THF cores via two kinds of one
      pot THF ring formation, respectively. In addition, the total synthesis of
      murisolin, which shows cytotoxic activity against human tumor cell lines with
      potency from 10(5) to 10(6) times that of adriamycin, was also achieved.

PMID- 15467276
TI  - [Comparison of biochemical properties and protein level of mevalonate
      pyrophosphate decarboxylase between stroke-prone spontaneously hypertensive rats
      and Wistar-Kyoto rats].
AB  - The spontaneously hypertensive rat (stroke-prone) (SHRSP) experiences severe
      hypertension and cerebral hemorrhage. The serum cholesterol level in this rat is
      lower than that in the normotensive Wistar-Kyoto rat. Epidemiologic studies have
      indicated a negative association between serum cholesterol level and the
      incidence of cerebral hemorrhage in humans. Therefore the low level of serum
      cholesterol in SHRSP may cause cerebral strokes. The following investigation
      demonstrated that the activity for the biosynthesis of cholesterol is decreased
      in SHRSP due to the reduced activity of mevalonate pyrophosphate decarboxylase
      (MPD). However, the mechanism underlying the reduced activity of this enzyme
      remains unclear. In this review, we indicate that the level of MPD in the brain
      and liver of SHRSP is reduced from the age of 2 weeks.

PMID- 15467277
TI  - [Investigation of cost and medical service fee for pharmaceutical management in
      home medical care].
AB  - Due to the evolvement of the aged society and the steep rise in medical costs,
      the environment encircling the medical care industry has been changing
      remarkably. For this reason, it has become both necessary and fundamental for a
      community pharmacist to participate in home medical care through the
      pharmaceutical management service. We have studied the associated costs and
      medical service fees for pharmaceutical management in home medical care. The
      costs and medical service fees were calculated based on the pharmaceutical
      management service data collected during the three years from November 1998 to
      October 2001. As a result, the medical service fees were calculated using the old
      system which lasted until March 2002. Calculations using this system took into
      account 550 points per visit, up to two visits per month. Under the new system
      which started in April 2002, the number of visits taken into account is four
      times a month, 500 points for the first visit, 300 points from the second through
      to the forth visit. Then, we simulated a break-even point (BEP). It is clear that
      it is difficult for any community pharmacy to be specialized in home medical
      care. In order for the pharmacist to actively participate in home medical care in
      the future, it is necessary to further improve the system.

PMID- 15467278
TI  - [Effect of glucose on luciferase expression in Photobacterium leiognathi].
AB  - Photobacterium leiognathi cultured in marine broth emits a luminescence that is
      temporarily enhanced and then extinguished by glucose. Glucose reduces the
      luciferase level and the expression of lux ABG mRNA in P. leiognathi. The amount
      of ATP in P. leiognathi is temporarily increased and then declines to the normal
      level. These results indicate that the extinguishing by glucose in P. leiognathi
      is induced by the interruption of the translation of luciferase.

PMID- 15467279
TI  - [Effects of nutrient solution concentration on inorganic and glycyrrhizin
      contents of Glycyrrhiza glabra Linn].
AB  - Licorice, Glycyrrhiza glabra Linn., is one of herbal medicines widely used for
      various purposes, including as a sweetener and for gastric ulcer treatment.
      However, environmental destruction due to the harvesting of wild licorice is
      becoming a serious problem. We cultured licorice in a hydroponic system to
      examine the relation between the concentration of nutritional solution applied
      and glycyrrhizin content to determine the optimal nutrient solution concentration
      for commercial licorice production. Licorice growth and glycyrrhizin content in
      the root reached the highest values when the plants received nutrient solution
      approximately equivalent to a quarter unit of Hoagland solution. The results also
      indicated that the glycyrrhizin content does not correlate with the concentration
      of nutrient solution applied and/or inorganic contents absorbed, i.e., licorice
      may absorb large amounts of nutrient solution but the glycyrrhizin content may
      not increase.

PMID- 15467280
TI  - Representative study for the evaluation of age- and gender-specific
      anthropometric parameters and blood pressure in an adolescent Hungarian
      population.
AB  - BACKGROUNDS/AIMS: To assess the age- and gender-specific anthropometric
      parameters and blood pressure in Hungarian adolescents. METHODS: A cross
      sectional study was performed between 1997 and 2000. Altogether 6,345 secondary
      school students (aged 15-18 years) were involved in the study. The representative
      sampling sites were selected randomly. In the capital city 3-stage and in the
      counties 4-stage stratified groups were assigned for the studies. Statistical
      analysis was performed using SPSS for Windows 9.0. RESULTS: The age- and gender
      specific percentile distributions are given with regard to body weight, body
      height, body mass index (BMI), waist circumference, waist-to-hip ratio and
      arterial blood pressure values. Elevated blood pressure values were found at the
      first recording in 14.1% of the boys and in 2.5% of the girls. Since it is well
      known that the arterial blood pressure (ABP) may exhibit considerable intra-
      individual fluctuation with time, we therefore categorized normotensive and
      hypertensive students on the basis of the mean ABP values calculated from data
      obtained during the course of the three separate consecutive measurement periods
      at least 2 weeks apart. After that, the incidence of high blood pressure was 7.5%
      in boys and 1.1% in girls. CONCLUSION: The age- and gender-specific cutoff values
      thus formed may serve as reference values to assess the risk of developing
      nutrition-related noninfectious diseases in the future on the basis of the
      present percentile distribution of BMI. The present study also provides data on
      the prevalence of hypertension in the 15- to 18-year-old age group.

PMID- 15467281
TI  - Influence of dietary curcumin, capsaicin and garlic on the antioxidant status of
      red blood cells and the liver in high-fat-fed rats.
AB  - BACKGROUND/OBJECTIVE: An animal study was carried out to examine the beneficial
      influence of known hypolipidemic spice principles - curcumin and capsaicin - and
      the spice garlic on the antioxidant status of red blood cells and liver tissue in
      hyperlipidemic rats. METHODS: Rats were rendered hyperlipidemic by maintaining
      them on a high-fat (30%) diet for 8 weeks. Spice principles - curcumin (0.2%) or
      capsaicin (0.015%) - or garlic (2.0%) were included in the diets of separate
      animal groups. Erythrocytes isolated at the end of the study were analyzed for
      intracellular antioxidant molecules and antioxidant enzymes. RESULTS:
      Intracellular total thiols in the erythrocytes of high-fat-fed rats were depleted
      significantly (16%). Similarly, the intracellular glutathione content in
      erythrocytes was depleted in high-fat-fed rats (28%). The concentration of lipid
      peroxides in the erythrocytes (intracellular as well as membrane) induced by
      H(2)O(2) was significantly higher in the high-fat-fed group. Curcumin (0.2%) or
      capsaicin (0.015%) or garlic (2.0%) in the diet which produced the
      hypotriglyceridemic effect were also effective in reducing oxidant stress, which
      was indicated by a significant countering of the depleted intracellular
      antioxidants - total thiols and glutathione - and elevated lipid peroxides in
      erythrocytes. The elevated lipid peroxide in blood plasma due to the high-fat
      diet was also significantly countered by the spice treatments. The severely
      depleted hepatic glutathione in high-fat treatment was also effectively reversed
      by dietary curcumin, capsaicin and garlic. CONCLUSIONS: Thus, dietary
      hypolipidemic spices were effective in reducing the oxidant stress, which was
      indicated by countering the depleted antioxidant molecules and antioxidant
      enzymes in erythrocytes and liver, and decreasing the elevated lipid peroxide
      content.

PMID- 15467282
TI  - The amount of dietary cholesterol changes the mode of effects of (n-3)
      polyunsaturated fatty acid on lipoprotein cholesterol in hamsters.
AB  - This study was designed to investigate the effects of the interaction between
      dietary (n-3) polyunsaturated fatty acids (PUFA) and different dietary
      cholesterol content on plasma and liver cholesterol in hamsters. Male Syrian
      hamsters consumed diets containing an incremental increase in dietary cholesterol
      content (0, 0.025, 0.05, 0.1 and 0.2%, w/w) with either (n-3) PUFA (21 g/100 g
      fatty acids) or (n-6) PUFA (37.4 g/100 g fatty acids) fat for 6 weeks. In
      hamsters fed the nonatherogenic diet (0 or 0.025% dietary cholesterol), very low
      density lipoprotein (VLDL)-cholesterol levels in the (n-3) PUFA group were not
      significantly different from those in the (n-6) PUFA group, and low density
      lipoprotein (LDL)-cholesterol levels in the (n-3) PUFA group were significantly
      lower than those in the (n-6) PUFA group. In contrast, in hamsters fed the
      atherogenic diet (0.1 or 0.2% dietary cholesterol), VLDL- and LDL-cholesterol
      levels in the (n-3) PUFA group were significantly higher than those in the (n-6)
      PUFA group, in a dose-dependent manner. When the hamsters were fed with 0, 0.025,
      0.05, 0.1 or 0.2% (w/w) dietary cholesterol, high density lipoprotein (HDL)
      cholesterol concentration was significantly lower in the (n-3) PUFA group than
      those in the (n-6) PUFA group. Hepatic cholesteryl esters were significantly
      lower, while hepatic microsomal acyl-coenzyme A:cholesterol acyltransferase
      activity and VLDL-cholesteryl esters were significantly higher in hamsters fed (n
      3) PUFA with the atherogenic diet (0.1 or 0.2% dietary cholesterol) than in those
      fed (n-6) PUFA with the atherogenic diet. Our results demonstrate that the amount
      of dietary cholesterol is an important factor in determining the mode and extent
      of effects of dietary (n-3) PUFA, especially on VLDL- and LDL-cholesterol levels.
      When dietary cholesterol intake was above 0.1% (w/w), the plasma cholesterol
      lowering effect of (n-3) PUFA disappeared, and instead, it showed a cholesterol
      increasing effect. However, the effects of dietary (n-3) PUFA on HDL-cholesterol
      are independent of dietary cholesterol content.

PMID- 15467283
TI  - Lipoprotein(a) and other cardiovascular metabolic risk factors in Kuwaiti
      children with type-1 diabetes.
AB  - BACKGROUND/AIMS: Lipoprotein(a) synthesis and catabolism could be influenced by
      insulin or by diabetes metabolic complications in patients with type-1 diabetes.
      The aim of the study was to investigate the relation of plasma lipoprotein(a)
      concentrations with metabolic cardiovascular risk factors in Kuwaiti children
      with uncomplicated type-1 diabetes. METHODS: This case-control study included 115
      (44 males and 71 females) diabetic children aged 6-18 years matched by age and
      sex to 115 non-diabetic children as controls. RESULTS: There was no significant
      difference between the mean lipoprotein(a) concentrations in type-1 diabetic
      children (27.34 mg/dl) and their controls (22.80 mg/dl). Total cholesterol,
      apolipoprotein A1 and B levels were significantly higher in diabetic children
      than controls. In diabetic children, significant correlations were found between
      lipoprotein(a) levels and glycated hemoglobin (r = 0.249, p = 0.011), total
      cholesterol (r = 0.208, p = 0.025), and apolipoprotein B (r = 0.349, p < 0.001).
      The proportion of diabetic children with lipoprotein(a) >30 mg/dl was
      significantly higher in those having poor glycemic control (glycated hemoglobin
      >9.0%, p = 0.013), raised total cholesterol (p = 0.033), or with a family history
      of cardiovascular disease (p = 0.006). CONCLUSION: Plasma lipoprotein(a) levels
      were not elevated in young type-1 diabetic children compared to non-diabetic
      controls; however, lipoprotein(a) levels were significantly higher in diabetic
      children with poor glycemic control. Moreover, there were significant
      correlations between lipoprotein(a) and the metabolic cardiovascular risk factors
      total cholesterol, atherogenic index, apolipoprotein B and apolipoprotein B/A1
      ratio.

PMID- 15467284
TI  - Effect of diabetes mellitus and different treatments on plasma and erythrocyte
      phospholipid fatty acid composition in type 2 diabetics.
AB  - AIM: The aim of the present study was to determine how the fatty acid composition
      of plasma and erythrocyte phospholipids is influenced by the diabetic condition
      and by dietary or glibenclamide treatment in type 2 diabetes. METHODS: The fatty
      acid composition of plasma and erythrocyte phospholipids is assessed in 3
      nonobese groups of Cuban diabetics with comparable age and BMI: 13 newly
      diagnosed, 15 on diet alone and 15 on diet/glibenclamide. Thirteen healthy
      individuals were used as controls. Fasting serum glucose, insulin and
      glycosylated hemoglobin and dietary fat intake were assessed. RESULTS: In plasma
      phospholipids, significant lower values were found for 14:0, 15:0 and 17:0 in
      newly diagnosed patients than in controls. In red blood cell phospholipids, 14:1,
      20:0 and 24:1 of newly diagnosed patients were significantly lower than of
      controls, and 16:1omega7 and 18:4omega3 were significantly higher. The different
      treatments had an effect on 18:0, 18:1t, 20:0 and total trans fatty acids in
      erythrocyte, but not in plasma phospholipids. CONCLUSIONS: Changes in plasma
      phospholipid fatty acids found in type 2 diabetics may be due to an 'adapted'
      dietary pattern, whereas those in erythrocyte phospholipids may be attributed to
      effects of the disease itself and may be susceptible to normalization by diet or
      glibenclamide.

PMID- 15467285
TI  - Sketches of otohistory part 4: a cell by any other name: cochlear eponyms.

PMID- 15467286
TI  - Poor frequency discrimination probes dyslexics with particularly impaired working
      memory.
AB  - Substantial difficulties in performing simple auditory discriminations were
      previously found in some individuals with a specific reading disability but not
      in others. This high variability in psychoacoustic performance raises the
      question of whether this difficulty is related to the reading deficit. Addressing
      this question, we compared adult dyslexics with and without difficulty in simple
      auditory discriminations, using 2-tone frequency discrimination as our probe. The
      distribution of their frequency discrimination scores was bimodal. On this basis,
      we divided our participants into subgroups having either poor or adequate
      psychoacoustic performance. Only dyslexics with poor psychoacoustic scores had
      significantly impaired verbal working memory compared to their matched controls.
      Furthermore, and only in this subgroup, working memory scores were correlated
      with both cognitive abilities and reading-related tasks. Consistent with the
      hypothesis that in this subgroup poor working memory impedes performance in a
      broad range of academically related tasks, we found that the majority of
      dyslexics in this subgroup had more extensive academic difficulties and
      consequently needed special support in schools. We propose that dyslexics with
      poor psychoacoustic abilities form a distinct subtype of dyslexia in which the
      core deficit is not specific to phonological components. For these individuals,
      poor verbal working memory may be the main impediment to success in academic
      environments.

PMID- 15467287
TI  - Across-site threshold variation in cochlear implants: relation to speech
      recognition.
AB  - Functional implications of across-site variation in detection thresholds in
      subjects with cochlear implants were evaluated by comparing thresholds to speech
      recognition performance. Detection thresholds for bipolar (BP) and monopolar (MP)
      stimulation of all available stimulation sites were assessed in 21 subjects with
      Nucleus CI24M and CI24R(CS) implants. We found significant negative correlations
      between speech recognition and within-subject across-site threshold variance for
      both BP and MP stimulation, but no significant correlation of speech recognition
      with mean threshold levels. These results suggest that across-site variance of
      detection thresholds could provide a useful early indication of the prognosis for
      speech recognition and might serve as an indicator for specific therapeutic
      approaches in individual subjects.

PMID- 15467288
TI  - Paraquat-induced hair cell damage and protection with the superoxide dismutase
      mimetic m40403.
AB  - Some forms of ototoxicity appear to be mediated primarily by the superoxide
      radical; however, the exact role the superoxide radical plays in cochlear damage
      is not well understood because most ototoxic drugs produce multiple reactive
      oxygen species. To characterize the role of the superoxide radical in cochlear
      damage and the protective effect of compounds that inactivate superoxide, we
      treated mouse cochlear organotypic cultures for 24 h with paraquat, an herbicide
      that produces high levels of superoxide. M40403, a highly specific, nonpeptidyl
      mimetic of superoxide dismutase, was added to some cultures to inactivate the
      superoxide radical generated by paraquat. The number of outer hair cells (OHC)
      and inner hair cells (IHC) systematically decreased with increasing concentration
      of paraquat (0.01-10 mM). M40403 (10 muM) significantly increased OHC and IHC
      survival in cultures treated with 0.01-1.0 mM of paraquat. These results suggest
      that excess production of superoxide radical is a sufficient condition for hair
      cell loss.

PMID- 15467289
TI  - Reciprocal neural connections between the central posterior/prepacemaker nucleus
      and nucleus G in the gymnotiform fish, Apteronotus leptorhynchus.
AB  - The central posterior nucleus of teleost fish is a cluster of neurons in the
      dorsal thalamus that plays an important role in controlling social behaviors. In
      the weakly electric gymnotiform fish, Apteronotus leptorhynchus, this nucleus
      forms a larger complex together with the prepacemaker nucleus, hence called
      central posterior/prepacemaker nucleus (CP/PPn). This complex is crucially
      involved in neural control of transient modulations of the electric organ
      discharge, which occur both spontaneously and in the context of social
      interactions. This control function is intimately linked to its pattern of
      connectivity with other brain regions. By employing an in vitro neuronal tract
      tracing technique, we have, in the present study, identified a novel reciprocal
      connection between the CP/PPn and a cell group situated in the region between the
      ventral thalamus and the inferior lobe. Despite the previous interpretation by
      other authors of this cell group as the glomerular nucleus, the lack of a
      projection of this nucleus to the hypothalamus, as also demonstrated in the
      present investigation, makes such a homology unlikely. We, therefore, interpret
      this nucleus as a brain structure of unknown homology in other teleosts and
      suggest 'nucleus G' to identify it.

PMID- 15467290
TI  - Interspecific allometry of the brain and brain regions in parrots
      (psittaciformes): comparisons with other birds and primates.
AB  - Despite significant progress in understanding the evolution of the mammalian
      brain, relatively little is known of the patterns of evolutionary change in the
      avian brain. In particular, statements regarding which avian taxa have relatively
      larger brains and brain regions are based on small sample sizes and statistical
      analyses are generally lacking. We tested whether psittaciforms (parrots,
      cockatoos and lorikeets) have larger brains and forebrains than other birds using
      both conventional and phylogenetically based methods. In addition, we compared
      the psittaciforms to primates to determine if cognitive similarities between the
      two groups were reflected by similarities in brain and telencephalic volumes.
      Overall, psittaciforms have relatively larger brains and telencephala than most
      other non-passerine orders. No significant difference in relative brain or
      telencephalic volume was detected between psittaciforms and passerines.
      Comparisons of other brain region sizes between psittaciforms and other birds,
      however, exhibited conflicting results depending upon whether body mass or a
      brain volume remainder (total brain volume - brain region volume) was used as a
      scaling variable. When compared to primates, psittaciforms possessed similar
      relative brain and telencephalic volumes. The only exception to this was that in
      some analyses psittaciforms had significantly larger telencephala than primates
      of similar brain volume. The results therefore provide empirical evidence for
      previous claims that psittaciforms possess relatively large brains and
      telencephala. Despite the variability in the results, it is clear that
      psittaciforms tend to possess large brains and telencephala relative to non
      passerines and are similar to primates in this regard. Although it could be
      suggested that this reflects the advanced cognitive abilities of psittaciforms,
      similar studies performed in corvids and other avian taxa will be required before
      this claim can be made with any certainty.

PMID- 15467291
TI  - Phototherapy and photo-oxidation in premature neonates.
AB  - OBJECTIVE: The potential for photo-oxidation during phototherapy in premature
      neonates was assessed by measuring parameters reflective of photo-oxidation.
      METHODS: Blood was sampled from premature neonates prior to, and after 4 and 24 h
      of phototherapy, respectively. Total plasma bilirubin (TPB), blood
      carboxyhemoglobin corrected for inspired carbon monoxide (COHbc) (a sensitive
      index of heme catabolism), blood thiobarbituric acid reacting substances (TBARS)
      (a measure of lipid peroxidation), and plasma protein carbonyls (representative
      of protein oxidation) were determined. Study measurements were compared with
      baseline values both for the entire study group, and also individually for
      subgroups < and > or = 1.5 kg birthweight, respectively. The percentage
      difference (%delta) between baseline and the 24-hour measurement was calculated
      for each parameter. RESULTS: Forty-one premature neonates (mean [+/- SD]
      gestational age 30.5 +/- 2.7 weeks and birthweight 1,499 +/- 448 g) were studied.
      Mean TPB values decreased from a baseline of 9.1 +/- 2.3 to one of 7.2 +/- 2.8
      mg/dl, p < 0.01, during the first 24 h of phototherapy. For the entire patient
      sample, neither COHbc, TBARS or protein carbonyl values increased significantly
      over baseline measurements: COHbc: 0.90 +/- 0.26% vs. 0.92 +/- 0.32%; TBARS: 19.0
      +/- 5.6 vs. 18.0 +/- 4.5 nmol/ml, and protein carbonyls 7.73 +/- 3.78 vs. 7.63 +/
      3.56 U/ml (baseline and 24-hour samples only are shown in the abstract).
      Similarly, for the entire group, %delta (mean, interquartile range) were not
      significantly different between COHbc [-3.77 (-15.89-17.65)%], TBARS [-7.47 (
      17.37-7.38)%], and protein carbonyls [-1.47 (-28.51-43.48)%], respectively. For
      subgroup analysis of neonates < or > or = 1.5 kg birthweight, respectively, no
      significant increases in COHbc, TBARS or protein carbonyls were documented. A
      significant increase in %delta for COHbc in the <1.5 kg birthweight subgroup
      compared with those > or =1.5 kg, possibly indicative of hemolysis, was not
      matched by similar changes in %delta for TBARS or protein carbonyls, and may
      therefore not be a result of photo-oxidation. CONCLUSIONS: Except for changes in
      %delta in COHbc alone and in the smallest babies only, overall, short term
      phototherapy in premature infants was effective in reducing TPB concentrations
      without associated evidence reflective of photo-oxidation.

PMID- 15467292
TI  - Role of antibiotics in management of non-ventilated cases of meconium aspiration
      syndrome without risk factors for infection.
AB  - There are limited data on the efficacy of antibiotics in the management for
      meconium aspiration syndrome (MAS). This purpose of the prospective randomized
      controlled clinical trial compared the infection-related outcome of non
      ventilated cases of MAS without perinatal risk factors for infection, treated
      with or without antibiotics therapy, as measured by the incidence of pneumonia
      and sepsis up to the age of 2 months. From January 1997 to July 2003, this study
      was carried out in our nursery. Infants with MAS without perinatal risk factors
      for infection and without ventilator use were randomly allocated to study and
      antibiotics groups after informed parental consent was obtained. The study group
      did not receive antibiotics, while the antibiotics group received antibiotics
      including ampicillin and gentamicin for 3 days until the blood cultures were
      negative, as was standard practice in the nursery. Other management and
      monitoring of MAS were the same in both groups. Of a total of 425 cases of MAS,
      119 cases were excluded because there were at risk for infection or respiratory
      failure needing ventilator support. The study group comprised 148 cases and the
      antibiotics group 158 cases. Among these patients, 127 from the study group and
      132 from the antibiotics group were followed up until 2 months of age. The
      profile of patients with respect to the method of delivery, the characteristics
      of meconium, Apgar score, sex, gestational age and birth body weight was similar
      in both groups. There were no significant differences in the duration of
      tachypnea, O2 supplementation and nasal continuous positive airway pressure
      (CPAP) between the two groups. Pneumothorax occurred in 4 cases in the study and
      7 cases in the control group. There was no mortality in either group. Blood
      cultures at 6 and 72 h of age were all negative in both the study and the
      antibiotics groups. No infant developed bacterial pneumonia, sepsis or meningitis
      in the follow-up program at 2 months of age. We conclude that antibiotic
      treatment did not affect the clinical course and outcome related to infection in
      MAS without perinatal risk factors for infection and without ventilator use. The
      role of antibiotics in the management of MAS may need to be reevaluated in a
      study with a larger sample size.

PMID- 15467293
TI  - Increased prevalence of factor V Leiden mutation in premature but not in full
      term infants with grade I intracranial haemorrhage.
AB  - OBJECTIVES: In the current prospective study our aim was to analyse the
      distribution of the factor V Leiden (G1691A) mutation in preterm and full-term
      neonates with grade I intraventricular haemorrhage and in control neonates. STUDY
      METHOD: A group of 125 individually selected neonates with grade I
      intraventricular haemorrhage and 128 controls were investigated. RESULTS: The
      allele frequency was 7.2% in the total population of affected infants while it
      was 3.9% in the controls (p < 0.05); the latter corresponds to an average
      European allele frequency in healthy populations. When the infants were grouped
      as premature (<2,500 g and < or =36 weeks of gestational age) and appropriate for
      gestational age full-term infants the statistical analysis revealed an increased
      prevalence of the mutation in the premature group (10% allele frequency vs. 4.8%
      in the controls, p < 0.05), and a normal prevalence in the mature group (4.6 vs.
      3.1%, respectively); therefore, the overall increase was due to the increase of
      incidence rate in preterm neonates. CONCLUSIONS: These data confirm our previous
      results and suggest that as the preterm and term infants differ from each other
      in haemorrhage susceptibility in many clinical particulars, carrying of the
      mutation has probably also a different impact in premature and in full-term
      infants with respect to the intraventricular haemorrhage.

PMID- 15467294
TI  - Cold perfluorochemical-induced hypothermia protects lung integrity in normal
      rabbits.
AB  - To test the hypothesis that intrapulmonary perfluorochemical (PFC) liquid may
      induce hypothermia, and to compare the effects of internal (IC), external (EC),
      and combined cooling techniques (EC + IC), 14 juvenile rabbits were randomized to
      EC by a cold blanket (4 degrees C, n = 5), IC by intrapulmonary cold PFC liquid
      lavage (4 degrees C, n = 5), or combined IC with PFC and EC (n = 4). Arterial
      blood gas, blood pressure, and lung mechanics were monitored, and lung histology
      was examined by light microscopy. The results showed that cooling rates and the
      time needed to be cooled down to 30 degrees C were significantly faster in EC and
      EC + IC than IC (p < 0.05). Blood gas analysis and cardiopulmonary function were
      within the normal range in all groups. Histological assessment revealed varied
      atelectasis in all lung regions in EC, whereas PFC-filled lungs (IC and EC + IC)
      demonstrated more homogenous expansion and no evidence of atelectasis. The
      results indicate that intrapulmonary PFC may be an effective technique to induce
      and/or augment hypothermia while supporting gas exchange, lung volume and
      pulmonary architecture.

PMID- 15467295
TI  - Process of measuring in clinical medicine--implications of different definitions
      in clinical therapeutic studies.
AB  - Often, the decision whether a patient can be considered as healthy or ill is very
      difficult and depends on measurements and the interpretation of the results.
      Therefore, it is necessary to build and establish devices that base on certain
      pre-considerations (who should assess the data, when and how should be measured).
      Additionally, these devices have to be valid, reliable and responsive. According
      to the literature we came to the conclusion that no uniform definition of what is
      'healthy' exists. Referring to mathematical considerations we show an approach to
      solve this problem especially when the device is a scale. Based on the quality of
      the scale and of certain pre-considerations normal ranges can be established that
      will help to distinguish whether patients are 'healthy' or 'ill'. In this short
      review we discuss the problem of the establishment of a cut-off level on the
      basis of devices and we try to point out a solution to solve the arising
      problems.

PMID- 15467296
TI  - Clinical and radiological findings in dominance of Santorini's duct.
AB  - BACKGROUND/AIMS: Few studies on Santorini's duct dominance, in which the ventral
      pancreatic duct is narrower than and anastomoses with Santorini's duct have been
      performed. We examined clinical and radiological findings in cases characterized
      by dominance of Santorini's duct. METHODS: We reviewed 3,800 cases of endoscopic
      retrograde cholangiopancreatography. Clinical and pancreatographic findings
      including caliber, course, terminal shape, and patency of Santorini's duct were
      examined in cases of Santorini's duct dominance. RESULTS: Twenty-nine cases were
      diagnosed as Santorini's duct dominant. Chronic pancreatitis, acute relapsing
      pancreatitis, pancreatic-type pain, and hyperamylasemia not associated with
      obvious pancreatitis were observed in 3, 1, 5, and 6 cases, respectively.
      Cholangiopancreatographic findings indicated congenital choledochal cyst (n = 2),
      branch fusion between the ventral and dorsal pancreatic ducts (n = 23), and
      normal pancreatic duct system characterized by a straight course through the body
      and tail to join the ventral pancreatic duct in the neck portion of the pancreas
      (n = 4). Regarding terminal shapes of Santorini's duct, cudgel type (n = 9) and
      spindle type (n = 8), which showed frequent patency, were observed significantly
      more frequently than in controls. Patency of Santorini's duct was observed in 90%
      (17/19). CONCLUSIONS: Many Santorini's duct-dominant cases exhibited branch
      fusion between the ventral and dorsal pancreatic ducts. Although Santorini's duct
      functions well in most cases in which it is dominant, pancreatitis or pancreatic
      type pain occurs in half of such cases due to relative impairment of function of
      the minor duodenal papilla.

PMID- 15467297
TI  - Effects of menstrual cycle on postoperative analgesic requirements, agitation,
      incidence of nausea and vomiting after gynecological laparoscopy.
AB  - BACKGROUND: Several studies have suggested that the menstrual cycle has an impact
      on postoperative nausea and vomiting (PONV). No previous study has evaluated the
      effect of the menstrual cycle on the incidence of postoperative agitation and
      analgesic/antiemetic requirements. METHODS: On the basis of the phase of the
      menstrual cycle [pre+/-menstrual (Pd 25-6), early follicular phase (Pd 8-12),
      ovulatory phase (Pd 13-15), and luteal phase (Pd 20-24)], 67 patients enrolled in
      this blinded, prospective study. Anesthesia was standardized. Fentanyl was given
      to the patients who had severe pain in the recovery room. The patients who had
      agitation were given midazolam. When pain intensity was >5 on the Visual Analog
      Scale, metamizol was administered in the Gynecology Department. A blinded
      anesthesiologist recorded episodes of PONV in the recovery room, and 2 and 24 h
      postoperatively. RESULTS: The opioid requirement and the frequency of agitation
      were similar in each group. Metamizol consumption was highest in the luteal phase
      (p < 0.05). The follicular and luteal phases were predictors for vomiting at
      recovery (p < 0.05 and p < 0.001, respectively). At the postoperative 2nd hour,
      nausea was higher in the follicular phase than in the other phases (p < 0.05) and
      the luteal phase was a predictor for retching (p < 0.001). At the postoperative
      24th hour, nausea was the common symptom in the luteal phase (p < 0.05). The need
      for ondansetron was highest in the luteal phase (p < 0.01). CONCLUSIONS: In
      conclusion, we suggest that the scheduling of all surgical procedures according
      to the menstrual phase may serve to reduce the incidence of PONV and
      metamizol/ondansetron consumption and hospital costs.

PMID- 15467298
TI  - Free IGF-I, IGFBP-1, and the binary complex of IGFBP-1 and IGF-I are increased
      during human pregnancy.
AB  - BACKGROUND/AIMS: To investigate changes in free insulin-like growth factor I (IGF
      I) and IGF-binding protein 1 (IGFBP-1) complexed IGF-I during human pregnancy.
      METHODS: Overnight fasting serum was obtained in a longitudinal design from 11
      women with non-complicated pregnancy at gestation weeks 6-10, 16-20, 24-28 and 35
      38 and, for comparison, 5 weeks post-partum. All samples were analyzed for total
      and free IGF-I and IGF-II, IGFBP-3 and IGFBP-3 proteolysis, total and non
      phosphorylated (np-) IGFBP-1, and IGFBP-1 complexed IGF-I. RESULTS: Total IGF-I
      was increased in late pregnancy (week 35-38) (p < 0.001), whereas free IGF-I was
      significantly increased by 77% already at week 6-10 (p = 0.004) and by 140% (p =
      0.002) at week 34-38, when compared to post-partum levels. At weeks 16-20 and 24
      28, levels of free IGF-I were not significantly different from post-partum
      levels. Significant IGFBP-3 proteolysis was detectable from week 6-10 and
      throughout pregnancy (p < 0.05). Total and np-IGFBP-1 were significantly
      increased from 16-20 weeks of pregnancy (both p < 0.05) and IGFBP-1 complexed IGF
      I was increased 2-fold from week 16-20 and throughout pregnancy (p < 0.05).
      However, the saturation of IGFBP-1 remained constant at 27-29% during the study.
      CONCLUSION: We found evidence of increased free IGF-I and increased IGF-I in
      binary complexes during pregnancy, possibly caused by IGFBP-3 proteolysis and
      decreased ternary complex formation.

PMID- 15467299
TI  - Fibered confocal fluorescence microscopy (Cell-viZio) facilitates extended
      imaging in the field of microcirculation. A comparison with intravital
      microscopy.
AB  - This study investigated the capability of fibered confocal fluorescence
      microscopy (FCFM) to provide in vivo microvascular observations. FCFM is
      specifically designed for in vivo in situ observation thanks to a probe composed
      of a fiber bundle and micro-optics having a diameter as small as 650 microm. In
      the first part of the study, we compared the main characteristics of FCFM with
      those of intravital fluorescence microscopy (IFM). A mouse cremaster preparation
      was used as a common basis to allow for imaging with both modalities. We
      discussed the feasibility of obtaining quantitative measurements usually provided
      by IFM in the context of FCFM: morphometry, capillary permeability, functional
      capillary density, vasoconstriction and dilation effects. In addition, the
      possibility to visualize fluorescent red blood cells or leukocytes was also
      evaluated. Phototoxicity issues and limitations of FCFM were also discussed. We
      showed that FCFM allows observations and measurements usually provided by IFM and
      that the real-time capability of the system, as well as the flexibility and small
      diameter of the optical probe enable micro-invasiveness and can extend imaging
      capabilities for in vivo in situ observations when compared to IFM.

PMID- 15467300
TI  - PDGF and IL-1beta upregulate cofilin and LIMK2 in canine cultured pulmonary
      artery smooth muscle cells.
AB  - Actin cytoskeleton reorganization is regulated by various actin-binding proteins.
      Cofilin is the principal filament-depolymerizing protein, whose activity is
      reduced upon phosphorylation by LIMK. Thus, LIMK and cofilin comprise a signal
      transduction module regulating actin turnover and myogenic tone in healthy
      vasculature. Novel functions of smooth muscle cells (SMCs) in the hypertensive
      pulmonary artery, such as increased motility and proliferation, are supported by
      the actin cytoskeleton. We therefore hypothesized that bioactive peptides that
      affect these SMC functions may also result in an upregulation of LIMK and cofilin
      expression. Semiquantitative RT-PCR and immunoblotting indicated that LIMK2 and
      cofilin mRNA and protein expression is upregulated in canine pulmonary artery
      SMCs (PASMCs) exposed to PDGF or IL-1beta (10 ng/ml). Inhibition of ERK MAPKs (U
      0126, 10 muM) or p38 MAPK (PD-169316, 10 muM), but not PI3Ks (LY-294002, 50 muM),
      reduced LIMK2 and cofilin gene expression stimulated by PDGF or IL-1beta.
      Inhibition of ROCK (Y-27632, 10 muM) reduced only the IL-1beta-stimulated LIMK2
      and cofilin expression. These novel observations in PASMCs indicate that LIMK2
      and cofilin expression can be induced by PDGF or IL-1beta. This parallel
      upregulation of LIMK2 and cofilin may have potentially broad functional
      significance for the progress of pulmonary artery disease.

PMID- 15467301
TI  - Nitric oxide and effect of a radical scavenger N-tert-butyl-alpha-phenylnitrone
      on stroke in a rat model.
AB  - To characterize the role of nitric oxide (NO) in stroke, NO was measured using an
      in vivo microdialysis technique and electron spin resonance spectrometry in
      malignant stroke-prone spontaneously hypertensive rats (M-SHRSP), stroke-prone
      spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY).
      The brain dialysate NO level was higher in SHRSP than in WKY. NO was not detected
      in M-SHRSP hippocampus microdialysate after stroke except after the
      administration of N-tert-butyl-alpha-phenylnitrone (PBN). In addition, very
      little NO was generated in M-SHRSP brain tissue with hemorrhage. These data
      demonstrate an association between NO and stroke in M-SHRSP. Further, PBN
      administration results in maintenance of NO levels after stroke in M-SHRSP.

PMID- 15467302
TI  - Effects of eplerenone, a selective aldosterone blocker, on the progression of
      left ventricular dysfunction and remodeling in rats with dilated cardiomyopathy.
AB  - Aldosterone blockade reduces morbidity and mortality in patients with heart
      failure. We studied the effects of eplerenone, a novel aldosterone blocker, on
      the progression of left ventricular dysfunction and remodeling in rats with
      dilated cardiomyopathy after autoimmune myocarditis. Twenty-eight days after
      immunization, the surviving Lewis rats were randomized to 1 month's oral
      treatment with low-dose eplerenone (group L), high-dose eplerenone (group H) or
      vehicle (group V). Five of 15 (33%) rats in group V and 3 of 15 (20%) rats in
      group L died during the course of treatment. High-dose eplerenone significantly
      reduced cardiomyocyte hypertrophy, heart weight and heart weight to body weight
      ratio. Eplerenone improved left ventricular function in a dose-dependent manner.
      Central venous pressure and left ventricular end-diastolic pressure were lower,
      and +/-dP/dt and fractional shortening were higher in group H than group V.
      Eplerenone also attenuated myocardial fibrosis and reduced left ventricular mRNA
      expressions of TGF-beta(1) and collagen-III. Our results indicate that treatment
      with eplerenone improved left ventricular dysfunction and attenuated left
      ventricular remodeling in rats with heart failure.

PMID- 15467303
TI  - To induce or not to induce labor: a macrosomic dilemma.
AB  - We assessed the effect of labor induction among parturients carrying macrosomic
      fetuses on the risk of a cesarean section (CS). The study population consisted of
      consecutive women with singleton fetuses weighing >/=4,000 g, delivered between
      1988 and 1999. A comparison was made between parturients who delivered after
      labor induction and those who delivered without labor induction. The Mantel
      Haenszel procedure was used to obtain the weighted odds ratios while controlling
      for confounding variables. During the study period, 4,755 women delivered
      macrosomic newborns in our institution. In 20% of the women (n = 951) labor was
      induced, while 80% of them (n = 3,804) delivered without labor induction. The
      women who delivered after labor induction were more likely to be nulliparous
      (18.0 vs. 10.0%; p < 0.001). In addition, these women had significantly higher
      rates of gestational diabetes (23.3 vs. 10.7%; p < 0.001), hypertensive disorders
      (10.1 vs. 5.3%; p < 0.001), hydramnios (17.4 vs. 9.9%; p < 0.001), and
      oligohydramnios (2.1 vs. 0.2%; p < 0.001). The CS rate was significantly higher
      among the patients who delivered after labor induction as compared with those in
      whom labor was not induced (17.8 vs. 11.9%; odds ratio 1.6, 95% confidence
      interval 1.3-1.9, p < 0.001). Stratified analysis using the Mantel-Haenszel
      technique was performed to control for confounders such as gestational diabetes,
      hypertensive disorders, previous CS, hydramnios, oligohydramnios, and
      nulliparity. None of these variables changed the significant association between
      induction of labor and CS. The induction of labor among women carrying macrosomic
      fetuses was found to be an independent risk factor for a CS.

PMID- 15467304
TI  - Fluoride varnishes in caries prevention.
AB  - The first fluoride varnishes were developed during the 1960s (Duraphat) sodium
      fluoride varnish) and 1970s (Fluor Protector) silane fluoride varnish) to prolong
      the contact time between fluoride and enamel. Fluoride varnishes adhere to
      enamel, and calcium fluoride formed after application acts as a long-term
      reservoir of fluoride. Currently Duraphat varnish is the most widely used topical
      fluoride for professional application in Europe, and the use of fluoride
      varnishes is increasing in the USA. Duraphat varnish has been effective in three
      decades of clinical studies, but the results of Fluor Protector varnish are
      inconclusive. The percent caries reductions found in the 1990s have generally
      been lower than those reported in earlier studies, probably because of the higher
      exposure to other preventive measures in the more recent studies. In studies
      comparing Duraphat varnish and APF gel, Duraphat varnish was equally or more
      effective than APF gel. Sealants were most effective in preventing occlusal
      caries. Four applications per year, or three weekly applications once a year,
      have been found to be effective. However, several studies have shown that two
      applications per year may provide comparable results. Application is fast and
      easy. Professional prophylaxis is not necessary, and the patient can leave
      immediately after the treatment. No acute toxicity has been reported after using
      any fluoride varnish.

PMID- 15467305
TI  - A novel germline mutation in the von Hippel-Lindau gene in patients in Kuwait.
AB  - OBJECTIVE: To determine the germline mutation in an extended family in which 1
      member was diagnosed clinically with von Hippel-Lindau (VHL) disease and to
      investigate 3 generations of the family. SUBJECTS AND METHODS: The polymerase
      chain reaction-single strand conformation polymorphism sequencing techniques were
      used to identify the germline mutation in the VHL gene in the patient and also to
      study 9 other members of the extended family over 3 generations. RESULTS: The
      patient and 3 other members of the family were shown to have the same mutation in
      the splice donor site of the first intron. The mutation was identified as IVS1 +
      1 G-->T. CONCLUSION: The findings of this study indicate the presence of VHL
      mutation in a Kuwaiti family with Arab parentage. It is hoped that the study
      would contribute to understanding the types of mutation in VHL in the Middle
      East. Its early detection and diagnosis would help in genetic counseling of VHL
      patients.

PMID- 15467306
TI  - The effect of finite spatial resolution on the measurement of cardiac phantom
      wall thickness in single photon emission computerized tomographic imaging.
AB  - OBJECTIVE: To devise and validate a method of estimating accurately myocardial
      wall thickness from cardiac images acquired with single photon emission
      tomography (SPECT). MATERIALS AND METHODS: We simulated the imaging process by
      convolving a spatial resolution function, experimentally determined for a
      clinical SPECT system, with rectangular profiles mimicking the myocardial walls
      for different thicknesses and separations. Wall thicknesses were estimated by
      fitting the resulting profiles to a linear superposition of two offset Gaussians.
      The method was validated by extensive computer simulation and by testing on real
      phantom images. RESULTS: Accurate estimates of the wall thickness of SPECT
      phantoms were obtained when the estimated thickness (using fitting to Gaussians)
      was deconvolved with the point spread function (PSF) of the imaging system using
      a look-up table. CONCLUSIONS: This method is a novel method of estimating wall
      thickness from cardiac images. It is particularly useful for small separations
      (e.g. at end systole and/or towards the apex of the heart) of walls that are
      narrow compared to the PSF of the imaging system.

PMID- 15467307
TI  - Up-regulation of cytoskeletal proteins in activated microglia.
AB  - OBJECTIVES: This study investigates how the tumor necrosis factor (TNF-alpha) and
      interleukin-1beta (IL-1beta) affect the morphology, organization, and expression
      of actin, beta-actin and tubulin in microglia. MATERIALS AND METHODS: Microglia
      cultures were prepared from neopallia of newborn mice. Immunofluorescence,
      immunoblotting, and ELISA studies were used. RESULTS: When microglia are treated
      with TNF-alpha, IL-1beta or a combination of both for 1-5 days, the majority
      change from an ameboid to a large, round and flat shape. F-actin and beta-actin
      isoform, which are diffusely arranged throughout the cytoplasm before
      stimulation, are reorganized into filamentous bundles underneath and parallel to
      the cell membrane, which projects into many ruffles. This organization is
      maintained even after withdrawal of the cytokines. The dense microtubule network
      of tubulin in nontreated microglia becomes less dense and extends to occupy the
      cytoplasm of the treated microglia. Immunoblotting shows that the amount of total
      actin, beta-actin isoform and tubulin increases in treated microglia. In
      addition, IL-1beta and a combination of both TNF-alpha and IL-1beta stimulate the
      release of IL-6 by microglia. CONCLUSION: This study suggests that TNF-alpha and
      IL-1beta have an effect on the expression of cytoskeletal proteins similar to
      some extent to that of LPS. The up-regulation of actin, beta-actin and tubulin
      may play a key role in the motility and recruitment of microglia to the area of
      central nervous system inflammation.

PMID- 15467308
TI  - Etiology and antibiotic susceptibility patterns of community-acquired urinary
      tract infections in a Kuwait hospital.
AB  - OBJECTIVE: The aim of this study was to determine the distribution and antibiotic
      susceptibility patterns of bacterial strains isolated from patients with
      community-acquired urinary tract infections (UTIs) at the Infectious Diseases
      Hospital, Kuwait. MATERIALS AND METHODS: The study was conducted over a 7-year
      period. Patient information was obtained from medical record files. Antibiotic
      sensitivity testing was performed by disk diffusion. E test and double disk
      diffusion methods were used to study the production of extended spectrum beta
      lactamases. RESULTS: Of the 14,042 urine samples processed, significant
      bacteriuria (>10(5) cfu/ml) was detected in 1,606 (11.4%). The majority (74.5%)
      of the isolates were from women while the remaining 25.5% were from men. The
      majority of infections (75%) were due to Enterobacteriaceae, coagulase-negative
      staphylococci (10.3%) and group B streptococci (8.7%). Among the gram-negative
      enteric bacilli high prevalence of resistance to ampicillin,
      amoxicillin/clavulanic acid, cephalothin, and trimethoprim/sulfamethoxazole was
      observed. Increasing resistance to ciprofloxacin and gentamicin was observed in
      E. coli isolates over the 7 years. Multiple resistance was detected in 53.8 and
      41% of E. coli and Klebsiella spp. strains, respectively. No glycopeptide
      resistant enterococci were isolated. CONCLUSION: This study revealed that
      Enterobacteriaceae were the predominant bacterial pathogen of community-acquired
      UTIs in Infectious Diseases Hospital, Kuwait. It also demonstrated an increasing
      resistance to ciprofloxacin, gentamicin and the production of extended spectrum
      beta-lactamase among UTI pathogens in the community.

PMID- 15467309
TI  - Hemostatic and fibrinolytic response to nasal desmopressin in hemodialysis
      patients.
AB  - OBJECTIVE: To evaluate the effect of desmopressin (DDAVP) on hemostatic
      parameters during dialysis and in the interval between dialysis sessions.
      SUBJECTS AND METHODS: Fifteen patients dialyzed twice weekly at least for 1 year
      and 15 healthy volunteers serving as a control group were enrolled in the study.
      Bleeding time, platelet count, prothrombin time, activated partial thromboplastin
      time, tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI
      1), euglobulin clot lysis time, protein C, protein S, fibrinogen, D-dimer, factor
      V, VII, VIII, IX, X and von Willebrand factor (VWF) values were studied at the
      beginning, at 2 and 4 h of dialysis with and without administration of DDAVP at a
      dose level of 2 microg/kg intranasally. RESULTS: After dialysis, bleeding time
      shortened, PAI-1 and fibrinogen levels were lower, while VWF and D-dimer levels
      were higher. After DDAVP administration, bleeding time, PAI-1 levels were
      significantly lower (p <0.01), while tPA, factor VIII and VWF levels increased
      significantly (p <0.001). CONCLUSION: The findings indicate that DDAVP can be
      used for patients on dialysis with serious bleeding.

PMID- 15467310
TI  - Effect of vitamin A against methotrexate-induced damage to the small intestine in
      rats.
AB  - OBJECTIVE: The aim of the present study was to examine whether or not the
      administration of vitamin A (VA) protects against methotrexate (MTX)-induced
      damage to small intestinal epithelium. MATERIALS AND METHODS: Sixty-three male
      Wistar albino rats, 10-12 weeks old, weighing 240-280 g, were divided into three
      groups: (1) controls, (2) rats receiving MTX treatment alone, and (3) rats
      receiving MTX plus VA treatment. A single dose of MTX (20 mg/kg MTX in 20 ml
      vehicle) was administered to the rats intraperitoneally. For MTX plus VA treated
      groups, retinol palmitate (VA) 5,000 IU/kg dissolved in 0.5 ml sunflower oil was
      administered by intragastric tube 3 days prior to MTX treatment and continued
      till the rats were sacrificed. The control group was treated with vehicle. Both
      control and MTX-alone groups were also treated with sunflower oil as a placebo.
      The rats were sacrificed on the 2nd, 4th and 6th day after MTX treatment. Tissue
      samples from the jejunum were taken for histopathological analysis. RESULTS: MTX
      treatment induced villus shortening and fusion, epithelial atrophy, crypt loss,
      inflammatory infiltrate in the lamina propria, and goblet cell depletion. The pre
      and post-treatment administration of VA decreased the severity of jejunal damage
      caused by MTX treatment. CONCLUSION: Our results confirmed that administration of
      VA decreased the MTX-induced damage to the small intestine. This protective
      effect of VA may have clinical applications in cancer chemotherapy.

PMID- 15467311
TI  - Relationship between Epstein-Barr virus-encoded RNA expression, apoptosis and
      lymphocytic infiltration in gastric carcinoma with lymphoid-rich stroma.
AB  - OBJECTIVE: To investigate the association of apoptosis with apoptotic proteins
      and Epstein-Barr virus (EBV) expression in gastric carcinoma with lymphoid-rich
      stroma (GCLRS) in order to clarify the relationship between lymphocytic
      infiltration, EBV expression and apoptosis in gastric carcinoma. SUBJECTS AND
      METHODS: We performed immunohistochemical stains for bcl-2, bax and in situ
      hybridization for EBV-encoded RNA and the terminal deoxynucleotidyl transferase
      mediated dUTP-digoxigenin nick end labeling technique using the 24 cases of GCLRS
      and 23 cases of gastric carcinoma with lymphoid-poor stroma (GCLPS) out of 1,635
      cases of gastric carcinoma. RESULTS: The prevalence of GCLRS was 1.47%
      (24/1,635). The prevalence of EBV involvement in GCLRS (79%, 19/24) was
      significantly higher than in GCLPS (8.7%, 2/23). Apoptosis was revealed in all
      cases and there was no statistical difference between GCLRS and GCLPS.
      Immunohistochemical expression for bcl-2 was revealed only in the cytoplasm of
      lymphocytes in all cases, but bax showed distinct expression in the cytoplasm of
      neoplastic cells in all cases. There was a significant correlation between bax
      expression and the apoptotic index (p <0.05). Lymphocytic infiltration was
      significantly correlated with the expression of EBV (p <0.05) but not with
      survival rate and apoptosis. Most of the GCLRS cases were rated as low clinical
      stage (stage IA or B) and seemed to have a good prognosis. CONCLUSIONS: These
      results support the hypothesis that EBV infection plays an important role in the
      tumorigenesis of GCLRS, which has a better prognosis than usual gastric
      adenocarcinoma although there was no significant difference in the apoptotic
      index between GCLRS and GCLPS.

PMID- 15467312
TI  - Screening of elevated glucose levels in gingival crevice blood using a novel,
      sensitive self-monitoring device.
AB  - OBJECTIVE: To test the feasibility of using gingival crevice blood (GCB)
      collected during routine periodontal examination to estimate blood glucose levels
      using a novel and very sensitive self-monitoring device (FreeStyle). SUBJECTS AND
      METHODS: Forty-six patients (20 male, 26 female; age range 12-56 years, mean age
      36 +/- 11 years) seeking dental treatment took part in the study. Three and 4
      patients reported diabetes mellitus type 1 and 2, respectively; 24 had
      gingivitis, of which 22 were moderate or advanced periodontitis. Periodontal
      probing depth (PD) and clinical attachment loss was measured at 6 sites of every
      tooth present, and bleeding on probing (BOP) was recorded. A site with profuse
      BOP was chosen for glucose determination. Measurements in GCB were compared with
      those of conventional capillary fingerstick blood (CFB). RESULTS: Sufficiently
      large GCB volumes provided glucometer readings in 32 cases (range 1.17-10.00
      mmol/l). The CFB readings ranged between 1.39 and 11.50 mmol/l. If low amounts of
      crevice blood prohibited a glucometer reading, significantly lower mean numbers
      of sites with BOP (26 vs. 67, p <0.001) and elevated PD > or =4 mm (2 vs. 21, p
      <0.05) were seen. Agreement between the two measurements was low, the mean
      difference was -1.22, and limits of agreement (1.96 times the standard deviation
      of differences) were +/-2.89 mmol/l. CONCLUSION: The present study failed to
      provide any evidence for the usefulness of GCB for testing blood glucose during
      routine periodontal examination.

PMID- 15467313
TI  - A unique form of polycythemia associated with minimal change disease.
AB  - OBJECTIVE: To present a case with nephrotic syndrome due to minimal change
      disease and polycythemia. CLINICAL PRESENTATION AND INTERVENTION: A 20-year-old
      female was admitted to our clinic for edema and severe proteinuria present with
      minimal change disease since the age of 7 years. Polycythemia was found during
      the last activation of nephrotic syndrome. The patient was placed on
      glucocorticoid therapy that caused disappearance of edema, proteinuria and
      polycythemia. Ten months later both hemoglobin and hematocrit levels were within
      normal range. CONCLUSION: This patient with nephrotic syndrome due to minimal
      change disease and polycythemia was successfully treated with glucocorticoid.

PMID- 15467314
TI  - Guillain-Barre syndrome in a patient with hereditary spastic paraparesis. A case
      report.
AB  - OBJECTIVE: To report the unusual occurrence of Guillain-Barre syndrome (GBS) in a
      case of hereditary spastic paraparesis (HSP) and describe its effect on the
      preexisting clinical picture as well as the importance of early recognition and
      treatment. CLINICAL PRESENTATION AND INTERVENTION: A 41-year-old man known to
      have HSP developed an acute and rapid deterioration of muscle power associated
      with paresthesia in both upper and lower limbs. Clinical examination revealed
      flaccid quadriparesis with areflexia. Nerve conduction studies were suggestive of
      demyelinating polyneuropathy and CSF analysis showed increased protein but no
      cells. The diagnosis of GBS was made in addition to HSP. The patient received
      intravenous immunoglobulins 20 mg/kg body weight/day for 5 days. He responded
      very well to the treatment clinically and neurophysiologically and thereafter, he
      reverted to the preexisting spastic picture of HSP. CONCLUSION: The peripheral
      demyelination with GBS was severe enough to obscure the preexisting clinical
      picture, but fortunately it responded very well to treatment. The clinical
      associations with HSP are widely variable, therefore it is very important to
      recognize acquired treatable causes of weakness in such patients in order to
      prevent an increase in disability.

PMID- 15467315
TI  - Acute liver failure due to Hodgkin's lymphoma.
AB  - OBJECTIVE: To describe an unusual case of acute liver failure due to Hodgkin's
      lymphoma. CASE PRESENTATION AND INTERVENTION: A 37-year-old man was admitted with
      jaundice and abdominal distension. Physical examination showed tender
      hepatosplenomegaly, ascites, grade I encephalopathy, left cervical (2 x 1 cm) and
      axillary (1 x 1 cm) lymph nodes. The laboratory data revealed elevated serum
      bilirubin, transaminases, lactate dehydrogenase, and coagulation defects.
      Initially, primary liver disease was considered, but a liver biopsy revealed
      infiltration of the liver by Hodgkin's lymphoma that was confirmed by lymph node
      biopsy. Hodgkin's lymphoma was of lymphocyte depletion type. CONCLUSION: This
      case demonstrates that in the presence of lymphadenopathy involving acute liver
      failure, hematological malignancies should be taken into consideration. Liver and
      lymph node biopsies should be performed as early as possible.

PMID- 15467316
TI  - Clinical and anatomic features of acardiac twins.
AB  - OBJECTIVE: To report 6 cases of acardiac twins, and to investigate prognostic
      factors that would lead to survival of the normal twin. SUBJECTS AND METHODS:
      During a 9-year period from 1993 to 2001, 6 cases of acardiac twins out of
      109,000 deliveries at the Maternity Center, Tunis, Tunisia were studied. Detailed
      inspection, X-rays, ultrasound and autopsies were performed. RESULTS: Prenatal
      diagnosis was made in only 1 case at 33 weeks of gestation. Rudimentary cardiac
      tissue was observed in 2 of the 6 perfused twins, and the cephalic pole was less
      developed than other parts of the body. Severe agenesis or hypoplasia of the
      thoracoabdominal organs was commonly observed. Many limb malformations were
      observed, with arms the most affected. One of the pump twins was stillborn, 3
      died between days 1 and 3 from respiratory distress, and 2 developed cardiac
      failure after birth and were treated with diuretics and digoxin, which led to a
      favorable outcome in only 1. The ratio of the weight of the acardiac to pump twin
      (TWR) ranged from 50 to 142%. CONCLUSION: The findings of this study indicate
      that acardia can be diagnosed by means of ultrasound in front of a monochorial
      twin pregnancy when one of the fetuses is deformed and has no cardiac activity.
      Heart failure and polyhydramnios, as well as a TWR greater than 50% are
      prognostic factors for the pump twin.

PMID- 15467317
TI  - Renal failure due to Bardet-Biedl syndrome. A case report.
AB  - OBJECTIVE: To describe a case of Bardet-Biedl syndrome involving renal failure
      and retinal dystrophy. CASE PRESENTATION AND INTERVENTION: A 50-year-old female
      patient presented to the emergency service with uremic symptoms and metabolic
      acidosis. Polydactyly, retinitis pigmentosa, obesity, strabismus, nistagmus and
      renal failure were found. Because she had end-stage renal failure, hemodialysis
      therapy was started. She has been well for 18 months, without any complication on
      hemodialysis. CONCLUSION: Bardet-Biedl syndrome should be considered in patients
      with polydactyly, retinitis pigmentosa and renal failure.

PMID- 15467318
TI  - Rare infiltrative lung diseases: a challenge for clinicians.
AB  - Rare diffuse infiltrative lung diseases are a challenge for clinicians,
      radiologists, and pathologists for at least three reasons: (a) their low
      incidence and prevalence hamper the acquisition of expertise and frequently the
      diagnosis is delayed; (b) therapeutic actions are mainly empirical and based on
      steroid use, and (c) pathogenetic events are difficult to explain and only
      recently new therapeutic measures taking advantage of innovative genetic and/or
      immunopathogenetic studies have been suggested. In this review rare diffuse lung
      disorders are briefly discussed (pulmonary alveolar proteinosis, inherited
      lipidoses, acute eosinophilic pneumonia, amyloidosis, pulmonary ossification,
      pulmonary alveolar microlithiasis). The list is obviously not exhaustive and
      arbitrarily chosen. The intent is, however, to emphasize that in this difficult
      field multidisciplinary expertise and the knowledge of the most recent
      pathogenetic mechanisms have the main role in diagnosis and treatment.

PMID- 15467319
TI  - Computed tomography imaging in pulmonary embolism--the other side of the medal.

PMID- 15467320
TI  - Progress through sound and vision.

PMID- 15467321
TI  - Impact of spiral computed tomography on the diagnosis of pulmonary embolism in a
      community hospital setting.
AB  - BACKGROUND: While the optimal role of spiral CT angiography (CTA) in the
      diagnosis of pulmonary embolism (PE) remains controversial, this technology is
      already being widely utilized in the community setting. OBJECTIVES: To assess the
      impact CTA has had on angiography utilization rates and the overall diagnostic
      rate of PE. METHODS: All patients evaluated for PE during a 4-year period were
      studied. PE was defined as either a high-probability V/Q scan, a positive
      conventional angiogram, or a CTA with emboli in the segmental or larger pulmonary
      vessels. Diagnostic rates of PE per 1,000 hospital admissions were determined and
      analyzed for time periods before and after the introduction of CTA. CT reports
      were compared with their concurrent chest radiograph (CXR) reports and additional
      findings that were not apparent on CXR were abstracted. RESULTS: The diagnostic
      rate of PE per 1,000 hospital admissions was 1.8 prior to the introduction of CTA
      and increased to 2.8 per 1,000 admissions after the introduction of CTA (p <
      0.0001). Total costs for diagnostic testing per PE diagnosis made went from US
      2,518 dollars to US 2,572 dollars. While the number of PE diagnosed by V/Q scan
      remained constant, the number of PE diagnosed by conventional angiography
      decreased while the number diagnosed by CTA increased. In patients with
      intermediate probability V/Q scan results, the percentage of patients receiving
      subsequent angiography (conventional or CTA) increased from 17 to 26% (p =
      0.043). When conventional angiography was performed, CT imaging of the chest
      still had to be ordered for other reasons 38% of the time. Additional information
      was obtained in 78% of cases when CTA was performed. CONCLUSIONS: Increased
      utilization of CTA was associated with an increase in angiography utilization
      rates and diagnostic rates of PE, was cost effective, and often provided
      additional, useful, and unanticipated diagnostic information.

PMID- 15467322
TI  - Evolving differences in the presentation of severe asthma requiring intensive
      care unit admission.
AB  - BACKGROUND: The prevalence of asthma in the community has been increasing. Asthma
      mortality has not followed the same pattern. Patients who present with a severe
      asthma exacerbation share many characteristics with patients who die from asthma.
      OBJECTIVE: We examined the differences in the presentation of severe asthma in
      adults admitted to a medical intensive care unit (MICU) over a 10-year interval.
      METHODS: We reviewed the records of the MICU at the Columbia Presbyterian Medical
      Center for all admissions with severe asthma for the period from January 2000 to
      December 2001. The data collected included the number of admissions per month,
      baseline characteristics, initial arterial pH and PCO(2), length of ICU stay, and
      complications. These data were compared with similar data obtained over the
      period 1990-1991. RESULTS: The number of MICU admissions per month for severe
      asthma decreased from 3.1 in 1990-1991 to 0.8 in 2000-2001. There was a trend
      toward a reduction in asthma severity as determined by a decrease in the initial
      arterial PCO(2) from 80 +/- 27 to 55 +/- 23 mm Hg and an increase in pH from 7.1
      +/- 0.14 to 7.23 +/- 0.14 (0.10 > p > 0.05 for both). There was 1 death from
      severe hypoxemia and respiratory acidosis in the earlier series and no asthma
      deaths in the later series. CONCLUSION: In our institution, there has been a
      decline in the number of patients with status asthmaticus requiring ICU admission
      over the past 10 years and a trend towards less advanced presentations with
      reduced levels of respiratory acidosis and decreased ICU length of stay. These
      changes may be related to improved medications, education, or access to care in
      the community.

PMID- 15467323
TI  - Exhaled nitric oxide and hydrogen peroxide concentrations in asthmatic smokers.
AB  - BACKGROUND: Cigarette smoking is associated with decreased nitric oxide (NO)
      production and increased oxidative stress in the airways. Exhaled NO levels are
      not higher in asthmatic smokers than in healthy non-smokers, and the value of
      exhaled NO for diagnosing asthma in smokers has been questioned. OBJECTIVES: To
      compare exhaled NO concentrations between healthy and steroid-naive and steroid
      treated asthmatic smokers and non-smokers. To also assess the acute effect of
      cigarette smoking on exhaled NO and hydrogen peroxide (H(2)O(2)) levels in
      asthmatic smokers. METHODS: Exhaled NO was measured by chemiluminescence and
      exhaled H(2)O(2) spectrophotometrically. In 7 steroid-naive asthmatic smokers
      exhaled NO and H(2)O(2) was measured both before and 15 min after smoking one
      cigarette. Data are given as median (range). RESULTS: Exhaled NO level was
      significantly higher in steroid-naive asthmatic smokers than in healthy smokers
      [7.7 (3.4-32.5) ppb vs. 3.2 (2.0-7.2) ppb, p < 0.001]. Exhaled NO values were
      lower in smokers than in non-smokers both in healthy subjects and in steroid
      naive asthmatic patients. Steroid-treated asthmatic smokers had a tendency for
      lower exhaled NO values [5.4 (1.7-12.0) ppb] compared to steroid-naive asthmatic
      smokers. Cigarette smoking caused an acute increase in exhaled H(2)O(2)
      concentrations together with a decrease in exhaled NO concentration. CONCLUSIONS:
      Our data suggest that an elevation in exhaled NO concentration is associated with
      asthma in smokers. This difference may be useful for diagnosing the disease in
      smokers, but its clinical value needs further evaluation. Acute increase in
      exhaled H(2)O(2) concentrations suggests that smoking increases the oxidative
      stress in the asthmatic airways.

PMID- 15467324
TI  - Low incidence of paradoxical bronchoconstriction with bronchodilator drugs
      administered by Respimat Soft Mist inhaler: results of phase II single-dose
      crossover studies.
AB  - BACKGROUND AND OBJECTIVES: Respimat Soft Mist Inhaler (SMI) is an innovative
      device that offers improved lung deposition and is an environmentally friendly
      alternative to conventional, chlorofluorocarbon-containing metered-dose inhalers
      (CFC-MDIs). The aqueous formulations of bronchodilator drugs administered from
      Respimat SMI contain low concentrations of ethylene diamine tetra-acetic acid
      (EDTA), a stabilising agent, and benzalkonium chloride (BAC), an antibacterial
      agent, both of which have been associated with bronchoconstriction when
      administered via nebulisers. The aim of this retrospective analysis was to
      compare the incidence of paradoxical bronchoconstriction with bronchodilator
      drugs administered via Respimat SMI or a CFC-MDI in patients with asthma or
      chronic obstructive pulmonary disease (COPD). METHODS: Nine randomised, active-
      and/or placebo-controlled, double-blind, crossover studies, in which asthmatic
      and COPD patients (n = 444 and n = 216, respectively) received a beta(2)-agonist
      and/or anticholinergic or placebo via Respimat SMI or CFC-MDI, were included in
      the analysis. The incidence of conditions indicative of paradoxical
      bronchoconstriction were collated and divided into four categories: (1)
      'bronchospasm'; (2) two or more of the following events: 'other respiratory
      adverse events', 'rescue medication use' or 'asymptomatic drop in forced
      expiratory volume in one second' (FEV(1)); (3) either 'rescue medication use' or
      'other respiratory adverse event'; (4) 'asymptomatic drop in FEV(1)'. RESULTS:
      The incidence of adverse events indicative of paradoxical bronchoconstriction was
      low in those patients using the Respimat SMI device, and similar to that seen in
      the CFC-MDI group. In addition, the incidence of adverse events indicative of
      paradoxical bronchoconstriction observed in the Respimat SMI group was similar
      for BAC + EDTA and BAC-only drug formulations. CONCLUSIONS: These studies
      demonstrate that, due to the extremely low absolute amounts of BAC and EDTA
      delivered to the lungs by the device, Respimat SMI is safe with regard to
      paradoxical bronchoconstriction in patients with asthma or COPD.

PMID- 15467325
TI  - Effects of isolated cycle ergometer training on patients with moderate-to-severe
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Pulmonary rehabilitation (PR) programs are beneficial to patients
      with chronic obstructive pulmonary disease (COPD), and lower-extremity training
      is considered a fundamental component of PR. Nevertheless, the isolated effects
      of each PR component are not well established. OBJECTIVE: We aimed to evaluate
      the effects of a cycle ergometry exercise protocol as the only intervention in a
      group of COPD patients, and to compare these results with a control group.
      METHODS: 25 moderate-to-severe COPD patients were evaluated regarding pulmonary
      function, respiratory muscle strength, exercise capacity, quality of life and
      body composition. Patients were allocated to one of two groups: (a) the trained
      group (TG; n = 13; 6 men) was submitted to a protocol of 24 exercise sessions on
      a cycle ergometer, with training intensity initially set at a heart rate (HR)
      close to 80% of maximal HR achieved in a maximal test, and load increase based on
      dyspnea scores, and (b) the control group (CG; n = 12; 6 men) with no
      intervention during the protocol period. RESULTS: TG showed within-group
      significant improvements in endurance cycling time, 6-min walking distance test,
      maximal inspiratory pressure and in the domain 'dyspnea' related to quality of
      life. Despite the within-group changes, no between-group significant differences
      were observed. CONCLUSION: In COPD patients, the results of isolated low-to
      moderate intensity cycle ergometer training are not comparable to effects of
      multimodality and high-intensity training programs.

PMID- 15467327
TI  - Effect of CO2 inhalation on central sleep apnea and arousals from sleep.
AB  - BACKGROUND: CO(2) inhalation reduces central sleep apnea (CSA) in patients with
      congestive heart failure (CHF) and idiopathic CSA. CO(2) is also a stimulus for
      cortical arousal, which has been linked to increased sympathetic nerve activity
      (SNA) and increased mortality in CHF patients with CSA. OBJECTIVE: We have tested
      the hypothesis that during sleep, inhalation of CO(2) sufficient to reduce the
      apnea-hypopnea index (AHI) would not reduce the arousal index (AroI). METHODS: In
      10 male patients with CSA (7 with CHF and 3 with idiopathic CSA), the inspired
      CO(2) concentration was increased to raise the sleeping end-tidal CO(2) by 2-4 mm
      Hg during established stage 2 sleep. Each intervention was maintained for a 10
      min period. Sleep stage was monitored with electroencephalograms,
      electrooculograms, submental electromyogram, airflow with pneumotachometer and
      respiratory effort and blood gases with oxygen saturation and end-tidal CO(2).
      During periods of air and CO(2) breathing, AHI and AroI were compared with paired
      t tests; patients acted as their own controls. RESULTS: Inhalation of CO(2)
      produced a significant reduction in AHI (mean +/- SEM) from 74.4 +/- 12.4
      events/h during air breathing to 25.8 +/- 7.8 events/h with CO(2) inhalation (p =
      0.002). However, the AroI was not significantly different between the two
      conditions, air 67.8 +/- 12.3 events/h and CO(2) inhalation 52.8 +/- 12.4
      events/h (p = 0.264). CONCLUSION: CO(2) inhalation reverses CSA but not arousals
      from sleep. Our findings highlight the need for treatment options that reduce
      both respiratory events and decrease arousals from sleep, with their associated
      SNA sequelae.

PMID- 15467328
TI  - Sleep apnea syndrome and diastolic blood pressure elevation during exercise.
AB  - BACKGROUND: Several studies assessing the role of obstructive sleep apnea
      syndrome (OSAS) as an independent risk factor for hypertension have produced
      conflicting results. Although the sleep apnea syndrome is associated with
      hypertension, there are no references regarding the blood pressure response of
      normotensive OSAS patients during exercise. STUDY OBJECTIVES: The aim of this
      study was to investigate the relationship between diastolic blood pressure (DBP)
      response during exercise and the severity of OSAS. METHODS: We performed exercise
      testing a day after polysomnography in 17 normotensive males who were admitted
      for the first time because of OSAS and in 10 normal subjects who were members of
      the same families. During maximal incremental exercise test (bicycle ergometry)
      oxygen consumption (VO(2)) and the DBP were estimated at rest and at peak
      exercise. VO(2) was also measured when DBP were 100 and 110 mm Hg. RESULTS: At
      peak exercise DBP was significantly higher in OSAS patients (115.3 +/- 9.2 mm Hg)
      than in normal subjects (101 +/- 8.4 mm Hg, p < 0.01). OSAS patients reached a
      DBP of 110 mm Hg with a significantly lower VO(2) than normal subjects (1,881.5
      +/- 703.4 vs. 1,972.3 +/- 108.6 ml/min, p = 0.045). VO(2) was not different
      between the two groups at a DBP of 100 mm Hg (1,211.2 +/- 371.7 vs. 1,536.6 +/-
      267.2 ml/min, p = 0.089) but OSAS patients had a significantly lower heart rate
      than normals (111.2 +/- 13 vs. 118.6 +/- 27.6, p = 0.009). None of the aspects of
      quality of life, according to the Nottingham Health Profile Questionnaire, Part
      1, were significantly different between patients and normal subjects.
      CONCLUSIONS: Normotensive OSAS patients develop DBP elevation at an earlier stage
      during exercise compared to normal subjects. This hypertensive response was not
      correlated with the severity (apnea-hypopnea index, oxygen desaturation
      parameters) of OSAS. DBP elevation could be a limiting factor of physical
      performance in this group of patients.

PMID- 15467326
TI  - Measured diffusion capacity versus prediction equation estimates in blacks
      without lung disease.
AB  - BACKGROUND: Lung volumes in African-Americans are on average 10-15% less than in
      Caucasians for the same height and are race corrected accordingly. Despite this
      fact, prediction equation estimates (PEE) of diffusion capacity of CO (DL(CO))
      developed in Caucasians are not adjusted for lung volume in the black population.
      This could result in healthy blacks being labeled as abnormal. OBJECTIVE: To test
      the hypothesis that healthy black subjects might be labeled as abnormal using
      three commonly used PEE of DL(CO) which are currently used in the United States.
      METHODS: Forty-two nonsmoking black subjects with no history of any disease
      underwent DL(CO) testing. Controls consisted of 12 healthy Caucasian volunteers
      and the prediction equations themselves. The single breath diffusion capacity was
      used with a Collins system. The measured diffusing capacity was compared with the
      Miller, Knudson, and Crapo PEE by entering age, gender, height and weight for
      each subject into the appropriate equation. Abnormal was defined as a DL(CO) <80%
      predicted. Methane gas dilution and body plethysmography were used to determine
      alveolar volume. Values in parentheses in the results section are DLCO adjusted
      for alveolar volume proportions. RESULTS: The average measured DL(CO) in blacks
      was 25.85 +/- 6.37 ml/min/mm Hg. This value was significantly different (p <
      0.01) compared to the predicted DL(CO) of 29.80 +/- 4.77, 36.45 +/- 6.64, and
      35.33 +/- 5.27 for the Miller, Knudson, and Crapo equations, respectively. This
      resulted in 14/42 (0/42), 33/42 (3/42), and 33/42 (9/42) DL(CO) (DL(CO)/VA)
      measurements being defined as abnormal using the Miller, Knudson, and Crapo
      prediction equations, respectively. In Caucasians, the average measured DL(CO)
      was not different from the Miller PEE. However, the measured DL(CO) was
      significantly lower than the Knudson and Crapo PEE, although less so than in
      blacks. This resulted in no Caucasian DL(CO) measurements defined as abnormal
      with the Miller PEE and some with the Knudson and Crapo PEE, but less so than in
      blacks. The measured alveolar volumes by methane dilution were slightly but not
      significantly decreased compared to those determined by plethysmography. Both
      measured values were significantly different (p < 0.01) compared to the predicted
      alveolar volumes of 6.19 +/- 0.91, 6.38 +/- 1.07, and 6.05 +/- 0.96 liters for
      the Miller, Knudson, and Crapo PEE in blacks, with no difference in predicted and
      measured lung volumes in Caucasians. The difference in predicted versus measured
      DL(CO) measurements in blacks was 13.2, 29.1, and 26.8%, respectively, for the
      Miller, Knudson, and Crapo prediction equations. These differences were similar
      to the reduction in predicted values of 22.5, 24.7, and 20.7% for the above
      mentioned prediction equations, respectively, versus the measured alveolar volume
      by methane (in blacks). A race correction (reduction) of the Miller PEE for
      diffusion of 12% resulted in only 2/42 DL(CO) measurements being labeled as
      abnormal. CONCLUSIONS: Current PEE for DLCO when used in healthy blacks can
      result in an abnormal reading in up to 50% or more of the time. This failure of
      the PEE is related to a reduction in lung volume in African-Americans that is not
      accounted for. One approach to overcome this problem, until separate PEE are
      developed in blacks, is to race correct the Miller PEE for diffusion by 12%. This
      reduces the DL(CO) error to less than 5% for this population.

PMID- 15467329
TI  - Serum CC-10 in inflammatory lung diseases.
AB  - BACKGROUND: Although Clara cell secretory protein (CC-10) has been ascribed an
      anti-inflammatory role in lung diseases, its precise role remains unclear.
      OBJECTIVE: To further our understanding of the role of CC-10 in inflammatory lung
      diseases, CC-10 protein levels were measured. METHODS: Sera or bronchoalveolar
      lavage (BAL) fluids were collected from patients with different inflammatory lung
      diseases including bronchial asthma, chronic obstructive lung disease (COPD),
      sarcoidosis, idiopathic interstitial pneumonia (IIP), chronic eosinophilic
      pneumonia (CEP), pneumonia and lung cancer. Serum CC-10 concentrations were
      measured by enzyme-linked immunosorbent assay using urinary protein-1 antibody.
      Then, the relationships between CC-10 concentrations and lung diseases were
      investigated. Immunohistochemistry was performed using lung biopsy samples.
      RESULTS: Increased serum CC-10 levels were recognized in IIP patients, while CC
      10 levels were decreased in bronchial asthma patients and CEP patients.
      Immunohistochemistry revealed an aberrant expression in areas of fibrosis in IIP
      patients. Serum CC-10 concentrations were not associated with severity among IIP,
      COPD, and sarcoidosis. In contrast, serum CC-10 concentrations were correlated
      with FEV(1)/FVC in bronchial asthma patients. CONCLUSIONS: Although the number of
      patients was quite limited, these data provide new insights into the role of CC
      10 in lung diseases, and the possibility that the CC-10 concentration in serum
      could be a new marker indicating the severity of bronchial asthma.

PMID- 15467330
TI  - Spirometric reference values in Tunisian children.
AB  - BACKGROUND: In Tunisia, there are no normal values of pulmonary function for
      healthy Tunisian children. OBJECTIVES: The purpose of this study was to set
      reference values for spirometric lung function in Tunisian children and to
      compare these results with other data sets. METHODS: Spirometric values were
      measured with a Minato portable spirometer in 1,114 asymptomatic, nonsmoking
      Tunisian children (581 boys and 533 girls) 6-16 years of age. Natural logarithmic
      values of lung function and standing height were used in the final regression
      model. RESULTS: Prediction equations for forced vital capacity (FVC), forced
      expiratory volume in 1 s (FEV(1)), FEV(1)/FVC x 100, maximum mid expiratory flow
      (MMEF 25-75%) and peak expiratory flow (PEF) for both sexes are presented with
      standing height as the dependent variable. Our data show a significant increase
      in lung function with standing height in both sexes. Comparing our results with
      recent data, values of FVC and FEV(1) in both sexes in the present study are
      close to those in European, white US and Asian children, whereas our values are
      higher than the Libyan ones. CONCLUSIONS: Healthy Tunisian children showed
      similar spirometric reference values compared to European, white US and Asian
      children. Thus, these standards of lung function could also be used in Tunisia.

PMID- 15467331
TI  - Safety and yield of ultrasound-assisted transthoracic biopsy performed by
      pulmonologists.
AB  - BACKGROUND: Transthoracic ultrasound (US) has gained popularity as a tool for
      visualizing pleural effusions and assisting thoracentesis or chest drain
      placement. In the absence of effusion, US just as well demonstrates solid masses
      involving or abutting the pleura, yet biopsy of such lesions is not widely
      performed by chest physicians. OBJECTIVE: To assess the feasibility and the
      safety of US-assisted cutting needle biopsy performed by chest physicians in
      routine practice. METHODS: Lesions involving or abutting the pleura > or =20 mm
      in diameter on US were sampled with a 14-gauge cutting needle under local
      anesthesia. Biopsy site, needle direction and depth of penetration were
      determined with US. The procedure was performed without direct US guidance in
      'free-hand' technique. RESULTS: Ninety-one patients underwent 96 cutting-needle
      biopsies for suspected peripheral lung tumors (n = 44, 46%), pleural-based (n =
      39, 41%), mediastinal (n = 10, 10%), or chest wall lesions (n = 3, 3%), which
      were single in 71%, multiple in 6% and diffuse in 23%. Sensitivity for malignant
      neoplasms (n = 65) was 85.5% and 100% for mesothelioma (n = 10). Pneumothorax
      occurred in 4%. CONCLUSIONS: US-assisted cutting-needle biopsy of lesions > or
      =20 mm in diameter is safe in the hands of pulmonologists. The yield for
      neoplastic disease including mesothelioma is high.

PMID- 15467332
TI  - The role of transcarinal needle aspiration in the diagnosis and staging of lung
      cancer: computed tomographic correlates of a positive result.
AB  - BACKGROUND: Transbronchial needle aspiration (TBNA) is used most frequently to
      assess subcarinal nodes because of its technical ease. OBJECTIVES: We conducted a
      prospective observational clinical study to define the indications for TBNA use
      for subcarinal nodes (transcarinal needle aspiration, TCNA) related to the nodal
      size by computed tomography (CT) of the chest. METHODS: One hundred and eight
      consecutive patients with lung cancer underwent TCNA at the time of initial
      diagnostic bronchoscopy within a 22-month period. RESULTS: TCNA was positive in
      21 of the patients. Only 1 of 75 patients (1%) with subcarinal nodes less than 10
      mm in short-axis diameter by CT had a positive result. TCNA for enlarged nodes,
      10 mm or greater, had a high positive yield of 61% (20/33). The procedure
      provided the only evidence of unresectable non-small cell lung cancer (stage IIIA
      N2 disease) in 3 patients and the sole pathological evidence for malignancy in 5
      patients. CONCLUSIONS: The high yield of positive TCNA results for enlarged
      subcarinal nodes contributes to the improvement of the overall diagnostic yield
      of bronchoscopy. We recommend that TCNA for enlarged subcarinal nodes on CT in
      patients with presumptive lung cancer should be performed routinely at the time
      of initial diagnostic bronchoscopy.

PMID- 15467333
TI  - A vanishing carina: a rare cause of cough.

PMID- 15467334
TI  - Granulocytic sarcoma of the tracheobronchial tree: bronchoscopic and pathologic
      correlation.
AB  - Granulocytic sarcoma (GS) is an extramedullary, solid tumor composed of immature
      granulocytic cells, which occurs in association with myeloproliferative or
      leukemic disorders. GS can precede, accompany, or complicate the presence of
      hematologic malignancy in the blood or bone marrow. The anatomic distribution
      commonly includes bone, nerve, lymph node, and skin, but may involve a variety of
      soft tissues. Pulmonary involvement is uncommon but may invade the parenchyma,
      pleura, mediastinum, and airways. We report a rare case of endobronchial
      granulocytic sarcoma with bronchoscopic and pathologic correlation.

PMID- 15467335
TI  - Urinothorax: case report and review of the literature with emphasis on
      biochemical diagnosis.
AB  - Urinothorax is a rare cause of transudative pleural effusion secondary to
      obstructive uropathy. We present a case of urinothorax after shock wave
      lithotripsy and review the literature. A total of 53 cases have been described
      previously, and in a few of them, the biochemical characteristics of the pleural
      fluid were detailed. In general, patients with urinothorax have low pH and
      glucose levels, and their lactate dehydrogenase level can be very high, resulting
      in misclassification of the effusion as an exudate. The average pleural fluid to
      serum creatinine ratio reported in 12 cases was 9.15 (range 1.09-19.8).

PMID- 15467336
TI  - Pulmonary hemorrhage complicating a typical hemolytic-uremic syndrome.
AB  - We describe a case of pulmonary bleeding and subsequent acute respiratory
      distress syndrome (ARDS) in a 20-month-old female suffering from a typical
      postdiarrheal hemolytic-uremic syndrome (HUS). Acute renal failure was treated
      early by peritoneal dialysis. It is of interest to underline that
      thrombocytopenia or any coagulative impairment was absent when this complication
      occurred, and spontaneous diuresis recovery was ongoing. All examinations failed
      to identify a unique site of bleeding in the main stem bronchi or trachea.
      Complete renal and clinical recovery was obtained in spite of this very uncommon
      complication. Intensivists should be aware of this rare and potentially fatal
      complication of typical (D+)HUS.

PMID- 15467337
TI  - Rare cause of diffuse lung fibrotic/nodular pattern in an asymptomatic child.

PMID- 15467338
TI  - Diagnosing cryptogenic fibrosing alveolitis.

PMID- 15467339
TI  - Outcomes research: an overview.
AB  - Outcomes research is increasingly important in contemporary medicine. Outcomes
      research differs from traditional clinical research in that outcomes are
      typically measured from the patient's perspective, and expanded measures of
      outcome are used, such as quality of life and cost-effectiveness. In this
      introduction to the special journal edition, the author will discuss the
      background behind outcomes research and describe several of its important
      aspects. Outcomes research consists of the clinical study of expanded, patient
      based outcomes, as well as the study of populations, databases, and the delivery
      of health care. Outcomes research also includes the development of validated
      instruments to assess patient-based outcomes, development of disease severity
      staging systems, identification of comorbid conditions, and meta-analysis.

PMID- 15467340
TI  - Validation of health status instruments.
AB  - Health status instruments are questionnaires that are utilized to assess changes
      in health status of individuals. These surveys are increasingly of importance as
      health care providers are challenged to justify treatment approach and rationale.
      Objective criteria (e.g. CT scan of the sinuses) can be used to determine whether
      there is clinical evidence of disease. However, the impact of the disease on the
      individual's life is not included in such a clinical assessment. The use of
      validated and reliable health instruments is directed at measuring this impact in
      a reproducible and valid fashion. In patient-centered research, 'experimental'
      conditions are constantly changing because we are dealing with human beings with
      values, feelings, and perspectives. It is especially important to use valid
      measurement tools when assessing these impacts. This article outlines the
      principles of the development and validation of health status instruments and
      offers examples of such instruments from the otolaryngology literature.

PMID- 15467341
TI  - Development of staging and stratification systems.
AB  - Physicians communicate with each other on a daily basis using staging and
      stratification systems, whether they recognize this or not. At a minimum, they
      help convey a wealth of information in communicating about patients and their
      disease; more sophisticated staging systems help physicians recommend therapy and
      prevention strategies for patients, or predict functional and survival prognoses
      in concordance with the current scientific evidence. The goal of this article is
      to discuss the purpose and rationale of staging or stratification systems, and to
      introduce the clinical and statistical development and evaluation of these
      systems. The practicing physician should be aware of basic methodologic
      principles in the development of staging systems that help ensure their quality
      and applicability, so that staging systems can help improve patient care.

PMID- 15467342
TI  - The impact of comorbidity on outcomes.
AB  - Patients often have other diseases, illnesses, or conditions in addition to the
      disease under study. These other medical conditions are referred to as
      comorbidity. Comorbidity can impact on diagnosis, prognosis, and selection of
      therapy. There are a variety of instruments available to measure the type and
      severity of comorbid ailments. Comorbidity information can be obtained from
      direct discussions with the patient, a review of the medical record, or from
      electronic databases that contain billing information. The method of comorbidity
      assessment can impact on the interpretation of results. Accurate comorbid
      information will improve the conduct of and generalizability of clinical trials,
      evaluation of outcomes from observational research, population-based
      epidemiological studies, and patient-physician communication.

PMID- 15467343
TI  - Meta-analysis.
AB  - Systematic reviews use explicit and reproducible criteria to assemble, appraise,
      and combine articles with a minimum of bias. Meta-analysis is a form of
      systematic review that uses statistical techniques to derive quantitative
      estimates of the magnitude of treatment effects and their associated precision.
      Valid meta-analyses address focused questions, use appropriate criteria to select
      articles, assess the quality and combinability of articles, provide graphic and
      numeric summaries, consider potential biases, and can be generalized to a
      meaningful target population. The rate difference, or absolute risk reduction, is
      the preferred measure of clinical effect size; the reciprocal tells the number
      needed to treat for one additional favorable outcome. The benefits of meta
      analysis over individual trials include greater precision, increased statistical
      power, and the ability to identify and explore diversity among studies. Threats
      to validity include heterogeneity, citation bias, publication bias, language
      bias, and variations in study quality. Because meta-analysis defines rational
      treatment expectations at a population level, it is an adjunct to, not a
      substitute for, clinical judgment in the care of individual patients.

PMID- 15467344
TI  - The use of population and database resources in outcome-based research.
AB  - Many patient management decisions an otolaryngologist makes every day stem from
      good patient- and population-based evidence. This paper will explore the topic of
      population/database research and how these studies are useful. We also examine
      the current literature on this subject, explore the strengths and weaknesses of
      these studies and provide information on the practical aspects of performing this
      type of research. Overall, this paper should provide both an understanding of and
      an incentive for those with an interest in database use and the development of
      outcome-based projects.

PMID- 15467345
TI  - Outcomes research in rhinology: chronic rhinosinusitis.
AB  - Measuring 'outcome' in rhinology has been challenging investigators for decades.
      With the introduction of patient-based, quality of life outcomes, investigators
      have developed rhinologic-specific outcomes tools for allergic rhinitis, nasal
      obstruction, and chronic rhinosinusitis. Outcomes research in rhinology, however,
      is a nascent field. This article focuses on outcomes research in the management
      of chronic rhinosinusitis, especially as it relates to endoscopic sinus surgery.
      Quality of life outcomes are addressed not only as outcomes but as measures of
      disease and how they relate to other commonly used measures of disease such as CT
      and endoscopy.

PMID- 15467346
TI  - Outcomes research in head and neck cancer.
AB  - Quality of life (QOL) considerations are uniquely important in head and neck
      oncology outcomes research due to the multidimensional impact of these tumors and
      their treatment. Patient variables, tumor variables and treatment variables must
      be considered comprehensively in order to maximize the validity of QOL outcome
      measures. There are a multitude of QOL instruments, which can be classified into:
      (1) general measures of health-related QOL, (2) general QOL instruments for
      patients with cancer, (3) disease-specific instruments for patients with head and
      neck cancer, (4) treatment-specific instruments and (5) symptom-specific
      instruments. This article will highlight commonly used validated QOL instruments
      in head and neck oncology.

PMID- 15467347
TI  - Outcomes research in otology.
AB  - Among the otolaryngologic subspecialties, otology has historically been at the
      forefront of outcomes research in our specialty. Many traditional outcomes
      reporting tools have been consistently employed in the study of otologic disease
      and treatment outcomes including standardized reporting schemes for Meniere's
      disease and facial nerve dysfunction. However, recent interest has surfaced in
      disease-specific quality-of-life outcomes measures for many otologic diseases
      such as sensorineural hearing loss, conductive hearing loss and suppurative
      otitis media. Several reliable and validated outcomes tools are available for the
      assessment of the impact on quality of life and treatment outcomes for common
      otologic afflictions that carry with them significant quality-of-life burdens.
      Furthermore, similar outcomes tools have been developed that allow a scientific
      appraisal of disease status and quality of life for dizziness and tinnitus, which
      have been traditionally difficult to quantify. Increasing familiarity with these
      outcomes tools will allow investigators to accurately assess and compare
      treatments for these otologic diseases and justify treatment initiatives in the
      future.

PMID- 15467348
TI  - Outcomes research in pediatric otolaryngology.
AB  - There are several validated outcomes instruments available for use in the
      pediatric otolaryngology population. These include instruments for otitis media,
      rhinosinusitis, tonsil and adenoid disease; sleep-disordered breathing, voice
      disorders and tracheotomy. In addition, several prospective outcomes studies have
      been performed on common pediatric otolaryngology conditions. These studies have
      typically indicated that the quality of life impact of diseases such as otitis
      media and recurrent tonsillitis is quite high, and that surgical treatments (such
      as tympanostomy tube placement and adenotonsillectomy) result in significant
      improvements in quality of life and disease-specific health status. In addition,
      cost-effectiveness studies of cochlear implantation have indicated that
      implantation is a very cost-effective intervention when performed in children.

PMID- 15467349
TI  - Immunologic aspects of chronic fatigue syndrome. Report on a Research Symposium
      convened by The CFIDS Association of America and co-sponsored by the US Centers
      for Disease Control and Prevention and the National Institutes of Health.
AB  - Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800,000
      Americans of all ages, races, socioeconomic groups and genders. The etiology and
      pathophysiology of CFS are unknown, yet studies have suggested an involvement of
      the immune system. A symposium was organized in October 2001 to explore the
      possibility of an association between immune dysfunction and CFS, with special
      emphasis on the interactions between immune dysfunction and other abnormalities
      noted in the neuroendocrine and autonomic nervous systems of individuals with
      CFS. This paper represents the consensus of the panel of experts who participated
      in this meeting. Data suggest that persons with CFS manifest changes in immune
      responses that fall outside normative ranges, but current research does not
      provide definitive evidence on whether these immune abnormalities are a cause or
      result of the illness. It has become clear that CFS cannot be understood based on
      single measurements of immune, endocrine, cardiovascular, or autonomic nervous
      system dysfunction. This panel encourages a new emphasis on multidisciplinary
      research into CFS.

PMID- 15467350
TI  - Vasoactive intestinal peptide can modulate immune and endocrine responses during
      lipopolysaccharide-induced acute inflammation.
AB  - OBJECTIVES: In many studies, it has been reported that vasoactive intestinal
      peptide (VIP) may play an important role in modulation of the immunological
      response. VIP can be produced by immunological cells, and also the receptors for
      this neuropeptide are present in many of these cells. The aim of our study was to
      estimate the effects of the administration of exogenous VIP on serum
      concentrations of proinflammatory cytokines [interleukin (IL)-6 and tumor
      necrosis factor (TNF)-alpha] and an anti-inflammatory cytokine (IL-10) during
      lipopolysaccharide (LPS)-induced acute inflammation. We also estimated the
      influence of VIP on pituitary [FSH, LH, TSH and prolactin (PRL)], thyroid (T3 and
      T4), adrenal (corticosterone) and gonadal (testosterone) hormones in response to
      LPS-induced acute inflammation. METHODS: Male Wistar-Kyoto rats were divided into
      four groups, which received, respectively, placebo (0.9% NaCl), LPS, VIP and VIP
      with LPS. The TNF-alpha and IL-6 serum concentrations were measured after 2 h
      from the time of the administration of the agents, IL-10 was measured after 4 h,
      and the pituitary, thyroid, adrenal and gonadal hormone concentrations were
      measured after 2 and 4 h. Cytokine concentrations were estimated using ELISA
      tests, and hormone concentrations were measured using RIA tests. RESULTS: In our
      experiments, LPS administration dramatically increased serum proinflammatory
      cytokine concentrations (TNF-alpha and IL-6) after 2 h and the anti-inflammatory
      cytokine (IL-10) after 4 h, as well as increasing the serum corticosterone
      concentration (after 2 and 4 h) and LH (after 2 h). LPS application decreased
      serum concentrations of T3 and TSH (both after 2 h), testosterone (after 2 and 4
      h), FSH after 4 h and PRL after 4 h. VIP administration decreased the serum IL-10
      concentration after 4 h and T3 concentration after 2 h and increased serum
      concentrations of FSH and corticosterone after 4 h. VIP administrated
      simultaneously with LPS decreased the LPS-induced increase in IL-6 and
      corticosterone concentrations (consecutively after 2 and 4 h). VIP also enhanced
      LPS-induced thyroid hormone (T3 and T4) suppression after 4 h and testosterone
      suppression after 4 h. CONCLUSION: We conclude that VIP can modulate not only
      immune responses but also hormonal responses during acute inflammation.

PMID- 15467351
TI  - The influence of immunomodulation on psycho-neuroimmunological functions in
      benign multiple sclerosis.
AB  - OBJECTIVES: In multiple sclerosis (MS), several neuroimmunomodulatory effectors
      are known, including melatonin. They are able to influence disease-related
      neurophysiogical changes (disability or impaired vision) as well as
      neuropsychological performance (e.g. cognition and depression). In this study we
      assessed the relationship between immunomodulation on psycho-neuroimmunological
      functions in benign multiple sclerosis. METHODS: We evaluated 26 young female
      patients with benign MS treated with/without immunomodulating therapies with
      regard to their physical disabilities (Expanded Disability Status Scale, EDSS),
      their visually evoked potentials (VEP), their plasma melatonin concentrations as
      well as their performance regarding emotional and cognitive tests and compared
      them with healthy matched controls. RESULTS: Patients with MS showed deficits in
      cognitive and emotional functions compared to healthy controls, which were in
      accordance with their increase in EDSS over time. However, in contrast to
      untreated patients, patients receiving immunotherapy showed significantly
      increased dysfunction with respect to actual mood (p = 0.02) and a tendency to
      increased depression scores (p = 0.072). However, neither treatment subgroup had
      cognitive deficits. In untreated patients, melatonin levels correlated with
      reduced scores in the cognitive tests (p = 0.045) but not with depression or VEP
      latencies. Patients with long-standing MS (>10 years) showed a significant
      correlation (p = 0.01) to their increased depression scores and their melatonin
      levels, but no correlation with VEP or cognitive dysfunction, compared to
      patients with shorter disease duration (< or =10 years). CONCLUSION: These
      results indicate that in MS all aspects of the psycho-neuroimmunological network
      can be affected. Despite the potential influence of immunomodulation on
      depression, no connection with melatonin representing the retinohypothalamic
      tract/pineal gland circuits could be detected. However, visual perception as well
      as visuoconstructive abilities were affected in MS patients. Neuropsychological
      tests in MS should concentrate on cognitive variables, which reflect the clinical
      status more accurately and may be used to monitor disease-modifying therapies.

PMID- 15467352
TI  - Inhalation of low-level formaldehyde enhances nerve growth factor production in
      the hippocampus of mice.
AB  - OBJECTIVE: The effects of low-level formaldehyde (FA) inhalation on the amount of
      nerve growth factor (NGF) in the hippocampus of immunized mice were studied.
      METHODS: Evaluation of NGF in the hippocampus was performed by ELISA and RT-PCR.
      RESULTS: Exposure to 80 and 400 ppb FA significantly increased the brain NGF
      levels in the immunized mice. Evaluation of the NGF levels in the hippocampus of
      immunized mice showed that 400 ppb FA significantly increased the NGF content.
      The RT-PCR evaluation also showed higher concentrations of hippocampal NGF mRNA
      in the mice exposed to 80 and 400 ppb FA with immunization. CONCLUSION: Exposure
      of immunized mice to low levels of FA significantly increases NGF levels in the
      hippocampus.

PMID- 15467353
TI  - IL-1 alpha and TNF-alpha expression in rat periapical lesions and dental pulp
      after unilateral sympathectomy.
AB  - OBJECTIVES: Apical periodontitis is an inflammatory disease characterized by bone
      resorption, and sympathetic nerves are known to modulate bone resorption and bone
      remodeling. Higher numbers of osteoclasts and larger periapical lesions have been
      observed after sympathectomy in rats, but the mechanisms underlying the
      inhibitory effect of sympathetic nerves on osteoclasts are unknown. This study
      aimed to test the hypothesis that sympathetic nerves inhibit the production of
      the bone-resorbing pro-inflammatory cytokines IL-1 alpha and TNF-alpha in rat
      periapical lesions. METHODS: Rats were unilaterally sympathectomized and apical
      lesions were induced by exposing the dental pulp of molar teeth to the oral
      microflora. We quantified the cytokines IL-1 alpha and TNF-alpha by enzyme-linked
      immunosorbent assay, and immunohistochemical analysis was done for qualitative
      localization. Pulp from intact incisor teeth was tested as a control. RESULTS: We
      showed that IL-1 alpha was increased, but not TNF-alpha, in the periapical
      lesions on the sympathectomized side. Both IL-1 alpha and TNF-alpha were
      expressed in unexposed pulp. TNF-alpha was significantly decreased in the
      denervated incisor pulp, whereas the level of IL-1 alpha remained unchanged.
      CONCLUSIONS: This study suggests that sympathetic nerves have an inhibitory
      effect on IL-1 alpha in periapical lesions and a stimulatory effect on TNF-alpha
      in the intact rat pulp.

PMID- 15467354
TI  - The role of asymmetry of nervous and immune systems in the formation of cellular
      immunity of (CBaxC57Bl/6) F1 mice.
AB  - We have previously shown the existence of functional asymmetry of the immune
      system and the role of brain hemispheres and different lobes of thymus in the
      development of humoral immune response in (CBA x C57Bl/6) F1 mice. The role of
      asymmetry of the nervous and immune systems in the formation of the cellular
      immune response [delayed-type hypersensitivity (DTH) reaction] in these mice has
      been studied in our work. In order to test the influence of asymmetry of the
      primary immune organs, thymus, on the cellular immune response, mice were
      thymectomized and then we studied the effect of the injection of cells from
      contralateral thymus lobes of right-dominant and left-dominant donors by motor
      asymmetry on how pronounced the DTH reaction in the back left paw was. The
      injection of thymocytes from right-dominant donors appeared to result in
      significant differences in DTH reaction between left- and right-handed mice. At
      the same time, our experiments failed to discover any pronounced role of thymus
      asymmetry in the formation of DTH reaction. In order to test the influence of
      asymmetry of peripheral immune organs, regional lymph nodes, on the regulation of
      cellular immune response, we compared the DTH reaction in left and right paws of
      mice. We found that the intensity of the DTH reaction to sheep red blood cells in
      the front paws of (CBA x C57Bl/6) F1 mice depends not only on whether the antigen
      is injected into the left or right paw but also on the motor asymmetry of the
      hemispheres. While comparing the DTH reaction in the back left and right paw of
      mice we showed that in both right- and left-handed mice it was much more
      pronounced in the left paw than in the right one. The data obtained testify to
      the functional asymmetry of bilateral lymph nodes located near the forming
      cellular immune reaction. Thus, the results obtained show that the intensity of
      DTH reaction in (CBA x C57Bl/6) F1 mice depends on the functional asymmetry of
      regional lymph nodes and motor of brain hemispheres. The thymus functional
      asymmetry is of slight importance in DTH reaction.

PMID- 15467355
TI  - Methionine-enkephalin stimulates hydrogen peroxide and nitric oxide production in
      rat peritoneal macrophages: interaction of mu, delta and kappa opioid receptors.
AB  - OBJECTIVE: Methionine-enkephalin (MET) modulates various functions of macrophages
      related to both immune and inflammatory reactions in a naloxone reversible
      manner, suggesting that opioid receptors are involved in the regulation of
      macrophage activity. Since an endogenous opioid ligand might interact with more
      than one type of opioid receptor, the receptor interaction determines its effect
      on a particular function. METHODS: In the present study we have investigated the
      involvement of different opioid receptor types/subtypes in MET-induced modulation
      of H(2)O(2) and NO production in macrophages. Thioglycollate-elicited or resident
      rat peritoneal macrophages were treated in vitro with MET and/or specific
      antagonists of delta(1,2), delta(1), delta(2), mu and kappa opioid receptors.
      RESULTS: MET increased H(2)O(2)production in phorbol myristate acetate-stimulated
      rat peritoneal macrophages mainly through delta(1) opioid receptor. MET also
      enhanced NO production in rat peritoneal macrophages stimulated with
      lipopolysaccharide through delta(1) and mu opioid receptors. The blockade of mu
      and kappa receptor facilitated a potentiating effect of MET on H(2)O(2) release,
      and blockade of kappa receptor further raised the MET-induced increase of NO
      production in macrophages. CONCLUSION: It is concluded that both negative and
      positive functional interaction between delta, mu and kappa opioid receptors
      regulate the influence of MET on H(2)O(2) and NO production in rat peritoneal
      macrophages.

PMID- 15467356
TI  - Dexamethasone downregulates chemokine receptor CXCR4 and exerts neuroprotection
      against hypoxia/ischemia-induced brain injury in neonatal rats.
AB  - OBJECTIVE: Hypoxia/ischemia (H/I) induces rapid and massive brain damage in
      neonatal rat brain, resulting in long-term consequences on structural and
      functional maturation of the central nervous system. Inflammatory mediators
      contribute to these permanent pathological changes, which are sensitive to
      corticoid treatments. Since the chemokine receptor CXCR4, specific for the SDF-1
      alpha/CXCL12 ligand, regulates both apoptotic and neuroregeneration processes,
      this receptor was quantified 2 days following H/I in neonatal rat brain in
      relation with dexamethasone (DEX) treatment. METHODS: Seven-day-old male rats
      were exposed to a 90-min hypoxia following unilateral carotid ligation (H/I) and
      were sacrificed 48 h later. Glucocorticoid-pretreated animals were injected
      subcutaneously 5 h prior to hypoxia with 0.5 microg/g DEX. Glial fibrillary
      acidic protein and cresyl violet staining were used for assessing the extent of
      brain lesion subdivided into necrotic and penumbra-like areas. The density of
      CXCR4 receptors was determined by quantitative autoradiography using [(125)I]SDF
      1 alpha as a ligand. RESULTS: The H/I resulted in a massive lesion ipsilateral to
      the carotid ligation, which was extended to cortical, striatal, hippocampal and
      thalamic areas, while the contralateral hemisphere remained apparently
      unaffected. DEX decreased the lesion size by reducing mainly the necrotic area.
      H/I induced a marked increase in CXCR4 receptor binding in the penumbra-like
      areas. DEX pretreatment decreased CXCR4 receptor density in the penumbra and
      attenuated astrocytosis. Furthermore, DEX strongly lowered mortality rate and
      reduced functional recovery time right after hypoxia. CONCLUSION: The rapid
      enhancement in CXCR4 chemokine receptor binding in the affected brain areas
      suggests that SDF-1 alpha/CXCR4 may play a role in the hypoxia-induced
      inflammatory reaction in the neonatal brain. Attenuation of CXCR4 expression and
      astrogliosis could contribute to the neuroprotective effect of DEX pretreatment
      via influencing the inflammatory cascade induced by H/I in the neonatal brain.

PMID- 15467357
TI  - Immune alterations induced by social defeat do not alter the course of an on
      going BCG infection in mice.
AB  - The timing for applying stressor and primary immunization is known to influence
      the nature of the immune alterations induced by stress. The aim of the present
      study was to investigate the consequences of a stress occurring several days
      after the beginning of a primary infection on the host resistance. For this
      purpose, we investigated the effects of repeated social defeat on the immune
      response of mice infected with BCG 11 days before. In vitro production of
      cytokines in response to LPS or tuberculin, and the sensitivity of spleen cells
      to corticosterone were assessed 8 days after the end of the stress. Bacterial
      growth was assessed in the spleen. We demonstrated that social defeat in BCG
      infected mice induced a long-term increase in IL-6 and IL-10 production in
      response to LPS but did not modify the sensitivity of spleen cells to
      corticosterone. Stress did not affect the specific response to BCG, as shown by
      the production of cytokines in tuberculin-stimulated cultures. Accordingly,
      social defeat was unable to influence the mycobacterial growth in vivo. These
      results support the hypothesis postulating that stress does not affect antigen
      specific response when it is applied after priming.

PMID- 15467358
TI  - Electric foot-shock stress drives TNF-alpha production in the liver of IL-6
      deficient mice.
AB  - OBJECTIVES: Accumulating evidence has shown that interleukin-6 (IL-6) has
      pleiotropic effects on a variety of biological functions, including its
      antiapoptotic potential during liver injury. Our previous work demonstrated that
      restraint stress-induced elevation of plasma IL-6 negatively regulates plasma
      tumor necrosis factor-alpha (TNF-alpha). Herein, we further clarified the
      mechanism underlying the above finding and investigated the effect of IL-6 on
      liver apoptosis triggered by stress. METHODS: Male C57BL/6J and IL-6-deficient
      C57BL/SV129 mice were exposed to 1 h of electric foot-shock stress. Thereafter,
      the serum, liver and spleen TNF-alpha levels were measured at several time
      points. Serum alanine aminotransferase (ALT), liver caspase-3 and terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) activities
      were analyzed to evaluate the severity of liver injury and apoptosis. RESULTS:
      The liver, but not the spleen, of the IL-6-deficient mice exhibited a significant
      increase in TNF-alpha level after stress in parallel with serum TNF-alpha
      elevation, whereas no such TNF-alpha responses were found in the wild animals. No
      significant differences in stress-induced elevation of serum ALT levels, liver
      caspase-3 activities and the number of TUNEL-positive hepatocytes were found
      between the wild and IL-6-deficient mice. CONCLUSIONS: Taken together, these
      results indicate that IL-6 may play a critical role in suppressing TNF-alpha
      production in the liver, thereby decreasing the blood TNF-alpha level. In
      contrast, IL-6 secretion was shown to have no protective effect on stress
      triggered liver injury.

PMID- 15467359
TI  - c-Fos expression in the rat cerebral cortex during systemic GvH reaction.
AB  - OBJECTIVE: It is becoming clear that the CNS receives signals from the peripheral
      immune system. In order to identify the areas of the brain that receive
      information about a specific immune response to allogeneic antigens, we studied
      the expression of c-Fos, a neural activation marker, in the cerebral cortex
      following the induction of a graft-vs.-host reaction (GvHR) in rats. METHODS: C
      Fos expression in the brain was studied by immunohistochemistry. GvHR was induced
      in (WKY x PVG)F(1) rats by injecting 5 x 10(8) spleen cells from PVG rats.
      Control rats received syngeneic cells. RESULTS: No c-Fos immunoreactivity (IR)
      was observed in animals undergoing GvHR in the nucleus tractus solitarii (NTS),
      the locus coeruleus (LC), the organum vasculosum of lamina terminalis (OVLT), the
      paraventricular nucleus (PVN) or the central amygdaloid nucleus (Ce). In
      contrast, 3 days after GvH induction c-Fos IR was observed in the piriform cortex
      and several other olfactory-related regions indicating the stimulation of the
      olfactory pathway during GvHR. Strong c-Fos IR was also observed in the occipital
      visual cortex of animals undergoing a GvHR, suggesting that GvHR can affect
      visual functions. In addition, GvHR induced c-Fos IR in the prefrontal cortex
      (Cg3, orbital cortex), a region that has interconnections with most sensory
      modalities. Double-staining studies indicate that the cells that express the c
      Fos signal are neurons. CONCLUSION: We have defined the distribution of brain
      neurons that are affected during the induction phase of GvHR. Our results also
      indicate that the integration and processing of information from the immune
      system at CNS levels involve different areas during different types of immune
      responses.

PMID- 15467360
TI  - Mismatch repair proteins: key regulators of genetic recombination.
AB  - Mismatch repair (MMR) systems are central to maintaining genome stability in
      prokaryotes and eukaryotes. MMR proteins play a fundamental role in avoiding
      mutations, primarily by removing misincorporation errors that occur during DNA
      replication. MMR proteins also act during genetic recombination in steps that
      include repairing mismatches in heteroduplex DNA, modulating meiotic crossover
      control, removing 3' non-homologous tails during double-strand break repair, and
      preventing recombination between divergent sequences. In this review we will,
      first, discuss roles for MMR proteins in repairing mismatches that occur during
      recombination, particularly during meiosis. We will also explore how studying
      this process has helped to refine models of double-strand break repair, and
      particularly to our understanding of gene conversion gradients. Second, we will
      examine the role of MMR proteins in repressing homeologous recombination, i.e.
      recombination between divergent sequences. We will also compare the requirements
      for MMR proteins in preventing homeologous recombination to the requirements for
      these proteins in mismatch repair.

PMID- 15467361
TI  - Studies on crossover-specific mutants and the distribution of crossing over in
      Drosophila females.
AB  - In Drosophila females, the majority of recombination events do not become
      crossovers and those that do occur are nonrandomly distributed. Furthermore, a
      group of Drosophila mutants specifically reduce crossing over, suggesting that
      crossovers depend on different gene products than noncrossovers. In mei-218
      mutants, crossing over is reduced by approximately 90% while noncrossovers and
      the initiation of recombination remain unchanged. Importantly, the residual
      crossovers have a more random distribution than wild-type. It has been proposed
      that mei-218 has a role in establishing the crossover distribution by determining
      which recombination sites become crossovers. Surprisingly, a diverse group of
      genes, including those required for double strand break (DSB) formation or
      repair, have an effect on crossover distribution. Not all of these mutants,
      however, have a crossover-specific defect like mei-218 and it is not understood
      why some crossover-defective mutants alter the distribution of crossovers.
      Intragenic recombination experiments suggest that mei-218 is required for a
      molecular transition of the recombination intermediate late in the DSB repair
      pathway. We propose that the changes in crossover distribution in some crossover
      defective mutants are a secondary consequence of the crossover reductions. This
      may be the activation of a regulatory system that ensures at least one crossover
      per chromosome, and which compensates for an absence of crossovers by attempting
      to generate them at random locations.

PMID- 15467362
TI  - Unique invasions and resolutions: DNA repair proteins in meiotic recombination in
      Drosophila melanogaster.
AB  - To ensure the accurate disjunction of homologous chromosomes during meiosis, most
      eukaryotes rely on physical connections called chiasmata, which form at sites of
      crossing over. In the absence of crossing over, homologs may segregate randomly,
      resulting in high frequencies of aneuploid gametes. The process of meiotic
      recombination poses unique problems for the cell that must be overcome to ensure
      normal disjunction of homologous chromosomes. How is it ensured that crossovers
      occur between homologous chromosomes, rather than between sister chromatids? What
      determines the number and location of crossovers? The functions of DNA repair
      proteins hold some of the answers to these questions. In this review, we discuss
      DNA repair proteins that function in meiotic recombination in Drosophila
      melanogaster. We emphasize the processes of strand invasion and Holliday junction
      resolution in order to shed light on the questions raised above. Also, we compare
      the variety of ways several eukaryotes perform these processes and the different
      proteins they require.

PMID- 15467363
TI  - A role for the MutL homologue MLH2 in controlling heteroduplex formation and in
      regulating between two different crossover pathways in budding yeast.
AB  - BACKGROUND AND AIMS: Mismatch repair proteins play important roles during meiotic
      recombination in the budding yeast Saccharomyces cerevisiae and most eukaryotic
      organisms studied to date. To study the functions of the mismatch repair protein
      Mlh2p in meiosis, we constructed mlh2Delta strains and measured rates of crossing
      over, gene conversion, post-meiotic segregation and spore viability. We also
      analysed mlh1Delta, mlh3Delta, msh4Delta, msh5Delta, exo1Delta and mus81Delta
      mutant strains singularly and in various combinations. RESULTS: Loss of MLH2
      resulted in a small but significant decrease in spore viability and a significant
      increase in gene conversion frequencies but had no apparent effect on crossing
      over. Deletion of MLH2 in mlh3Delta, msh4Delta or msh5Delta strains resulted in
      significant proportion of the "lost" crossovers found in single deletion strains
      being regained in some genetic intervals. We and others propose that there are at
      least two pathways to generate crossovers in yeast (Ross-Macdonald and Roeder,
      1994; Zalevsky et al., 1999; Khazanehdari and Borts, 2000; Novak et al., 2001; de
      los Santos et al., 2003). Most recombination intermediates are processed by the
      "major", Msh4-dependent pathway, which requires the activity of
      Mlh1p/Mlh3p/Msh4p/Msh5p as well as a number of other proteins. The minor
      pathway(s) utilizes Mms4p/Mus81p. We suggest that the absence of Mlh2p allows
      some crossovers from the MSH4 pathway to traverse the MUS81-dependent pathway.

PMID- 15467364
TI  - Homologous recombinational repair proteins in mouse meiosis.
AB  - Eukaryotic meiotic recombination requires numerous biochemical processes,
      including break initiation, end resection, strand invasion and heteroduplex
      formation, and, finally, crossover resolution. In this review, we discuss
      primarily those proteins involved in the initial stages of homologous
      recombination, including SPO11, MRE11, RAD50, NBS1, DMC1, RAD51, RAD51 paralogs,
      RAD52, RPA, RAD54, and RAD54B. Focusing on the mouse as a model organism, we
      discuss what is known about the conserved roles of these proteins in vertebrate
      somatic cells and in mammalian meiosis. We consider such information as gene
      expression in gonadal tissue, protein localization patterns on chromosomal cores
      in meiocyte nuclei, and information gleaned from mouse models.

PMID- 15467365
TI  - Roles of RecA homologues Rad51 and Dmc1 during meiotic recombination.
AB  - RecA protein is involved in homology search and strand exchange processes during
      recombination. Mitotic cells in eukaryotes express one RecA, Rad51, which is
      essential for the repair of double-strand breaks (DSBs). Additionally, meiotic
      cells induce the second RecA, Dmc1. Both Rad51 and Dmc1 are necessary to generate
      a crossover between homologous chromosomes, which ensures the segregation of the
      chromosomes at meiotic division I. It is largely unknown how the two RecAs
      cooperate during meiotic recombination. In this review, recent advances on our
      knowledge about the roles of Rad51 and Dmc1 during meiosis are summarized and
      discussed.

PMID- 15467366
TI  - Inter-sex variation in synaptonemal complex lengths largely determine the
      different recombination rates in male and female germ cells.
AB  - Meiotic chromosomes in human oocytes are packaged differently than in
      spermatocytes at the pachytene stage of meiosis I, when crossing-over takes
      place. Thus the meiosis-specific pairing structure, the synaptonemal complex
      (SC), is considerably longer in oocytes in comparison to spermatocytes. The aim
      of the present study was to examine the influence of this length factor on
      meiotic recombination in male and female human germ cells. The positions of
      crossovers were identified by the DNA mismatch repair protein MLH1. Spermatocytes
      have approximately 50 crossovers per cell in comparison to more than 70 in
      oocytes. Analyses of inter-crossover distances (and presumptively crossover
      interference) along SCs suggested that while there might be inter-individual
      variation, there was no consistent difference between sexes. Thus the higher rate
      of recombination in human oocytes is not a consequence of more closely spaced
      crossovers along the SCs. The rate of recombination per unit length of SC is
      higher in spermatocytes than oocytes. However, when the so-called obligate
      chiasma is excluded from the analysis, then the rates of recombination per unit
      length of SC are essentially identical in the two sexes. Our analyses indicate
      that the inter-sex difference in recombination is largely a consequence of the
      difference in meiotic chromosome architecture in the two sexes. We propose that
      SC length per se, and therefore the size of the physical platform for crossing
      over (and not the DNA content) is the principal factor determining the difference
      in rate of recombination in male and female germ cells. A preliminary
      investigation of SC loop size by fluorescence in situ hybridization (FISH)
      indicated loops may be shorter in oocytes than in spermatocytes.

PMID- 15467367
TI  - Novel and diverse functions of the DNA mismatch repair family in mammalian
      meiosis and recombination.
AB  - The mismatch repair (MMR) family is a highly conserved group of proteins that
      function in genome stabilization and mutation avoidance. Their role has been
      particularly well studied in the context of DNA repair following replication
      errors, and disruption of these processes results in characteristic
      microsatellite instability, repair defects and, in mammals, susceptibility to
      cancer. An additional role in meiotic recombination has been described for
      several family members, as revealed by extensive studies in yeast. More recently,
      the role of the mammalian MMR family in meiotic progression has been elucidated
      by the phenotypic analysis of mice harboring targeted mutations in the genes
      encoding several MMR family members. This review will discuss the phenotypes of
      the various mutant mouse lines and, drawing from our knowledge of MMR function in
      yeast meiosis and in somatic cell repair, will attempt to elucidate the
      significance of MMR activity in mouse germ cells. These studies highlight the
      importance of comparative analysis of MMR orthologs across species, and also
      underscore distinct sexually dimorphic characteristics of mammalian recombination
      and meiosis.

PMID- 15467368
TI  - Meiotic recombination intermediates and mismatch repair proteins.
AB  - Mismatch repair proteins are a highly diverse group of proteins that interact
      with numerous DNA structures during DNA repair and replication. Here we review
      data for the role of Msh4, Msh5, Mlh1, Mlh3 and Exo1 in crossing over. Based on
      the paradigm of interactions developed from studies of mismatch repair, we
      propose models for the mechanism of crossover implementation by Msh4/Msh5 and
      Mlh1/Mlh3.

PMID- 15467369
TI  - Cytological studies of meiotic recombination in human males.
AB  - We combined immunostaining and fluorescence in situ hybridization (FISH)
      methodology to directly examine meiotic exchanges in over 2,000 pachytene stage
      spermatocytes from 25 individuals. Our results indicate that, on average, there
      are about 50 exchanges per cell and that, with the exception of the acrocentric
      chromosomes, all chromosome arms harbor at least one exchange. We also identified
      significant among-individual variation in the mean number of exchanges, with an
      approximate 20% difference between individuals with "low" and those with "high"
      exchange frequencies.

PMID- 15467370
TI  - The mammalian mid-pachytene checkpoint: meiotic arrest in spermatocytes with a
      mutation in Atm alone or in combination with a Trp53 (p53) or Cdkn1a (p21/cip1)
      mutation.
AB  - ATM, the protein product of the gene mutated in the human autosomal recessive
      disorder ataxia telangiectasia, is involved in detection of double strand breaks
      (DSBs) and is a key component of the damage surveillance network of cell cycle
      proteins. In somatic cells ATM phosphorylates many other proteins including p53,
      an important regulator of cell cycle control. Mice deficient for Atm are male
      sterile with arrest and apoptosis occurring at testis epithelial stage IV, which
      in normal spermatocytes corresponds to mid-pachynema. Unlike the situation in
      somatic cells, we find no evidence that disruption of the Trp53 (p53) gene, or
      its down-stream target Cdkn1a (p21/Cip1) results in even a partial rescue of the
      Atm defect.

PMID- 15467371
TI  - Substitution of Pichia pastoris-derived recombinant proteins with mannose
      containing O- and N-linked glycans decreases specificity of diagnostic tests.
AB  - BACKGROUND: Recombinant proteins from Pichia pastoris need to be fully evaluated
      before used as diagnostic tools. OBJECTIVE: The objective of this study was to
      investigate whether glycosylation by P. pastoris interferes with the specificity
      of diagnostic tests. METHODS: An autoantigen involved in Wegener's disease
      (protease 3) and 2 major inhalant allergens from grass pollen (Dac g 5) and house
      dust mite (Der p 1) were produced as recombinant molecules in P. pastoris. O
      linked glycans on Dac g 5 were characterized by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. The immune reactivity of
      the recombinant proteins was compared to that of their natural counterparts by
      ELISA and a radio-allergosorbent test (RAST) as well as by ELISA and RAST
      inhibition. RESULTS: In contrast to the non-glycosylated natural allergen,
      recombinant Dac g 5 was shown to carry at least 2 small mannose-containing O
      glycans. We showed that both these O-glycans and the N-linked glycans on
      recombinant protease 3 and recombinant Der p 1 were recognized in ELISA by IgG
      antibodies in sera of healthy individuals. These IgG responses were closely
      correlated. The natural autoantigen and allergens were not recognized by IgG
      antibodies from healthy subjects. The carbohydrate nature of the epitopes
      recognized by IgG on the recombinant proteins was confirmed by inhibition studies
      with mannose and yeast mannan. IgE recognition of yeast glycans was observed in 2
      out of 9 positive sera from patients with allergic bronchopulmonary
      aspergillosis. CONCLUSION: Production of recombinant molecules in yeast (or
      moulds) can introduce IgG-binding glycans that negatively affect the specificity
      of diagnostic tests.

PMID- 15467372
TI  - Mast cell tryptase activates peripheral blood eosinophils to release granule
      associated enzymes.
AB  - BACKGROUND: Mast cells and eosinophils are important effector cells in asthma.
      Understanding their interactions is essential for studying asthma
      pathophysiology. Inflammatory mediators released from mast cells, such as
      arachidonic acid metabolites, TNF and IL-5, are important in eosinophil biology.
      However, little is known about the effects of mast cell-specific mediators, such
      as tryptase, on eosinophils. Our objective was to investigate the effects of mast
      cell tryptase on human peripheral blood eosinophils. METHODS: Peripheral blood
      eosinophils isolated from asthmatic individuals were activated using various
      concentrations of tryptase- and protease-activated receptor-2 (PAR-2)-activating
      peptides (PAR-2 AP). Eosinophil activation was evaluated by the release of
      granule mediators, superoxide release, estimation of eosinophil survival, changes
      in intracellular Ca2+ concentration and mitogen-activated protein kinase
      activation. RESULTS: Tryptase induced the release of eosinophil peroxidase and
      beta-hexosaminidase from peripheral blood eosinophils but had no effect on RANTES
      release. Eosinophils isolated from two thirds of our donors responded to
      tryptase, while the remainder appeared not to respond. Release of granule
      mediators was dependent on tryptase enzymatic activity. To identify the mechanism
      of eosinophil activation by tryptase, we studied the expression of PAR-2 by
      eosinophils and its function. Using RT-PCR, we amplified PAR-2 from eosinophils.
      However, flow cytometry failed to detect significant PAR-2 expression on the
      surface of eosinophils. The PAR-2 AP SLIGRL-NH2 did not induce eosinophil
      activation by any of the methods we employed. CONCLUSION: Our data indicate that
      mast cell tryptase may affect eosinophil activation status independently of PAR
      2.

PMID- 15467373
TI  - The anti-allergic effects of lactic acid bacteria are strain dependent and
      mediated by effects on both Th1/Th2 cytokine expression and balance.
AB  - BACKGROUND: There is growing interest in the immune-stimulating effect and in
      particular, the anti-allergic effect, of lactic acid bacteria (LAB). However, no
      comprehensive studies have been done that compare the immune-stimulating
      potential of LAB strains. METHODS: The in vitro immune-stimulating effects on
      Th1/Th2 balance of more than 100 LAB strains were compared in splenocytes from
      ovalbumin-sensitized Th2-polarized mice. The in vivo anti-allergic ability of
      strain KW3110 was studied in the Th2-polarized model by detecting serum IgE
      concentration, Th1/Th2 cytokine secretion from splenocytes, and the expression of
      co-stimulatory molecules on macrophages. RESULTS: In vitro studies from Th2
      polarized splenocytes, using IL-12 as a Th1 parameter and IL-4 secretion as a Th2
      parameter revealed a wide variety of IL-12-inducing and IL-4-repressing
      activities, depending on the strain of LAB, not depending on the species.
      However, evaluation of individual strains in vivo revealed that after exposure to
      Lactobacillus paracasei KW3110 strain, the serum IgE elevation elicited by
      repeated OVA injection of mice was strongly inhibited. Cytokine secretion from
      splenocytes 20 weeks after KW3110 administration showed increased IL-12 and
      decreased IL-4 expression. Both CD40 and B7-1 expression on macrophages was
      upregulated by administration of KW3110. CONCLUSIONS: Improving the consequences
      of the Th1/Th2 imbalance by administration of LAB was dependent upon the LAB
      strain rather than the LAB species. Oral KW3110 administration in the mouse
      allergy model directed the Th1/Th2 balance toward Th1 through the maturation of
      APCs and inhibition of serum IgE elevation.

PMID- 15467374
TI  - Relationship between active and passive smoking and total serum IgE levels in
      Japanese women: baseline data from the Osaka Maternal and Child Health Study.
AB  - BACKGROUND: Many studies have shown that cigarette smoking is associated with
      elevated concentrations of total serum IgE. Few studies, however, have examined
      total IgE in relation to passive smoking exposure, especially in adults. This
      cross-sectional study investigated the association of active and passive smoking
      exposure with levels of total serum IgE in Japan. METHODS: Study subjects were
      981 pregnant women in Osaka. Total IgE levels were measured using UniCAP 1000 and
      were defined as elevated if they exceeded 170 ml/UI. Age, gestation, parity,
      family history of asthma, atopic eczema and allergic rhinitis, indoor domestic
      pets, family income, education and the mite allergen level in house dust were
      selected as potential confounding factors. RESULTS: Current smoking of at least
      15 cigarettes a day and 8.0 or more pack-years of smoking were independently
      related to an increased prevalence of elevated total serum IgE (adjusted odds
      ratios 3.40 and 2.51, 95% confidence intervals 2.12-5.47 and 1.55-4.06,
      respectively), and both cigarette smoking status and pack-years of smoking were
      significantly positively associated with total serum IgE levels, especially in
      subjects with a positive familial allergic history. There was no measurable
      association of exposure to environmental tobacco smoke (ETS) at home or at work
      with total serum IgE concentrations among those who had never smoked.
      CONCLUSIONS: Our results corroborate a positive relationship between active
      smoking and total serum IgE levels; however, this study failed to substantiate a
      positive association of ETS exposure with total IgE. Investigations with more
      precise and detailed exposure measurements are warranted.

PMID- 15467376
TI  - A normal organ antigen and its corresponding antibodies in pathological human
      sera.
AB  - Previous studies on the appearance in pathological human sera of antibodies to an
      antigen of normal mammalian organs were continued. In gel precipitation
      reactions, antibodies combining with saline extracts of mammalian organs were
      found in 20 of 63 cancer sera and in 4 of 15 syphilis sera, but only in 3 of 56
      other pathological sera. Furthermore, an identical antigen was demonstrated in 5
      of 58 pathological sera. The antigen under study did not belong to any group of
      known heterophile antigens and it was devoid of organ and tissue specificity.

PMID- 15467375
TI  - Synthesis and secretion of interleukin-15 by freshly isolated human bronchial
      epithelial cells.
AB  - BACKGROUND: Interleukin-15 (IL-15), which shares many functional activities of IL
      2, is proposed as a potential modulator of T and natural killer (NK) cell
      mediated inflammatory diseases. Since IL-15 gene is expressed in various cell
      types including epithelial cells, we examined how proinflammatory modulators
      affect IL-15 gene expression in both freshly isolated human bronchial epithelial
      cells (HBECs) and the human bronchial epithelial cell line BEAS-2B. METHODS:
      HBECs were obtained from 25 patients with primary lung cancer by bronchial
      brushing under bronchofiberscopy. The expressions of IL-15 and its receptor were
      examined using reverse transcription-polymerase chain reaction (RT-PCR), Northern
      blot analysis and enzyme-linked immunosorbent assay. RESULTS: IL-15 mRNA was
      constitutively expressed in the cells and was upregulated by several
      proinflammatory cytokines such as IL-1beta, tumor necrosis factor-alpha,
      interferon-gamma (IFN-gamma) and lipopolysaccharide. In addition, IFN-gamma but
      not other cytokines induced the synthesis and secretion of IL-15 protein.
      Investigation of IL-15 receptor expression using RT-PCR showed that IL-15Ralpha
      and IL-2Rbeta chains but not IL-2Ralpha or gamma chain were constitutively
      expressed in these cells. CONCLUSIONS: Bronchial epithelial cells may contribute
      to T and NK cell-mediated airway inflammation through IL-15 production.

PMID- 15467377
TI  - Strategies for palliative care in advanced colorectal cancer.
AB  - Palliative care has appropriately been receiving increased attention in recent
      years. From the surgeon's standpoint, therapy is considered palliative when
      resection of all known tumor sites is no longer possible or advisable. Since a
      cure, as commonly defined, is not possible, the goal of treatment and eventually
      the success of therapy becomes judged by the control of symptoms and alleviation
      of suffering. Providing optimal palliative care for the patient with advanced
      colorectal cancer is a complex and challenging process. The process of providing
      palliative care may be a departure from the traditional surgical satisfaction
      derived from the complete excision of a malignancy, but surgeons achieving
      excellence in palliative care will likely find this a rewarding endeavor.

PMID- 15467378
TI  - Cushing's syndrome: adrenalectomy and long-term results.
AB  - BACKGROUND: The objective of this study was to assess the preoperative symptoms,
      intra- and postoperative complications and follow-up in patients after uni- or
      bilateral adrenalectomy due to Cushing's syndrome (CS), independent of etiology.
      METHODS: Clinical charts of 42 patients (5 with ACTH-dependent, 37 with ACTH
      independent CS) were reviewed, and follow-up data were obtained from re
      examination of the patients. RESULTS: The symptoms most frequently seen were
      hypertension, changes of the skin and obesity. Eight bilateral and 36 unilateral
      adrenalectomies were carried out without any intraoperative complications.
      Postoperative complications occurred in 5 patients, 1 patient died on the fourth
      postoperative day. After a mean duration of 4.6 years 28 of 41 patients could be
      re-examined, 5 patients had died. One patient showed recurrence 4.3 years after
      unilateral adrenalectomy due to nodular hyperplasia, contralateral adrenalectomy
      again revealed nodular hyperplasia. CONCLUSION: Early diagnosis is essential in
      order to decrease the rate of pre-, intra- and postoperative complications.
      Endoscopic approach should be taken in a specialized center due to poor patient's
      condition. Recurrent disease on the contralateral side may represent bilateral
      adrenal hyperplasia with sequential tumor formation, demonstrating the importance
      of extensive preoperative biochemical and imaging testing and close follow-up.

PMID- 15467380
TI  - Frameless localization for functional neurosurgical procedures: a preliminary
      accuracy study.
AB  - BACKGROUND: Targeting for functional stereotactic procedures is traditionally
      carried out in a noninteractive fashion, without real-time positional feedback.
      In addition, stereotactic frames are uncomfortable for patients and may impede
      intraoperative neurological evaluation. As an initial step toward a fully
      frameless approach to functional surgery, we have investigated the use of an
      image-guided microdrive coupled to a stereotactic frame system. METHODS: For
      initial laboratory tests, a stereotactic phantom was imaged using high-resolution
      CT scanning. Three representative targets were chosen within the phantom.
      Targeting was carried out in the usual fashion using the StealthStation planning
      suite, utilizing the Radionics CRW system. An LED-equipped reference arc was
      attached to the CRW base ring. Registration of the base ring was accomplished
      using a spherical probe. A custom-built microdrive was fitted with an LED array,
      mounted on the CRW arc and tracked by the StealthStation. The distance between
      the Stealth real-time localization and the CRW localization was measured on
      screen. To evaluate the accuracy of the system in the operating room, a similar
      procedure was carried out in 13 functional neurosurgical operations (pallidotomy
      or deep brain stimulator placement). RESULTS: Errors of localization in the
      laboratory setting ranged from 0.53 to 0.70 mm. In 11 operative cases, the
      average difference between the CRW localization and the Stealth localization was
      1.77 mm. In the remaining 2 cases, equipment malfunction prevented measurement of
      localization error. CONCLUSIONS: Frameless image-guided localization compares
      favorably to targeting performed noninteractively. In addition, real-time
      positional feedback confers advantages in target region visualization and
      confidence in placement of lesions and stimulators for functional procedures.
      With small improvements in accuracy and system reliability, fully frameless
      functional procedures could be safely carried out.

PMID- 15467381
TI  - Co-registration of the Schaltenbrand-Wahren microseries with the probabilistic
      functional atlas.
AB  - OBJECTIVE: The Schaltenbrand-Wahren atlas (SWA) is anatomical, sparse and
      inconsistent in three dimensions. A high-resolution, electrophysiology-based
      atlas derived from numerous specimens overcomes these limitations. A combined
      anatomy-physiology atlas leverages the strengths and complementarity of both,
      which is studied here. METHOD: An electronic version of the SWA was constructed.
      A probabilistic functional atlas (PFA) was developed from electrophysiological
      and neuroimaging data with 0.25 mm3 resolution. A combined atlas is constructed
      by co-registering the PFA with the SWA by applying linear scaling along the
      intercommissural distance and the height of the thalamus. RESULTS: An anatomy
      physiology atlas is superior to its component atlases. When in register, the
      anatomical and functional atlases are displayed together and used simultaneously.
      A structure of interest from the PFA can be displayed with high resolution,
      compensating for its sparseness in the SWA, while its surrounding structures are
      obtained from the SWA. The best anatomical and functional targets can be
      compared: for the subthalamic nucleus, the horizontal and lateral coordinates of
      the SWA-based and PFA- based targets are approximately the same, while the latter
      is located 1.3-1.5 mm more anteriorly. CONCLUSION: An anatomy-physiology atlas
      may enhance the accuracy of targeting and increase the neurosurgeon's confidence.
      It also opens new research avenues to serve as a reference for: (1) constructing
      an extendable atlas by adding new electrophysiological data, (2) comparing
      anatomical and functional targets, (3) studying and comparing various symptoms,
      and (4) comparing image-based targets obtained from various modalities.

PMID- 15467382
TI  - Safety and efficacy of tiered limited-dose gamma knife stereotactic radiosurgery
      for unilateral acoustic neuroma.
AB  - Stereotactic radiosurgery has become a more widely employed modality of treatment
      for acoustic neuromas, but controversy still arises regarding the safety and
      efficacy of the technique. In general, radiation doses have been reduced over
      time. Since beginning treatments of acoustic neuromas with the Gamma Knife at the
      University of Miami/Jackson Memorial Medical Center in 1994, a dose regimen was
      adopted by the first author employing limited doses selected on the basis of
      tumor size with the anterior and medial regions of the prescription isodose
      surface kept just inside the gadolinium-enhanced limit of the tumor, in order to
      protect the facial nerve and brainstem. The records of patients treated for
      unilateral tumors were retrospectively reviewed. Fifty-two patients, aged 23-83
      years, were treated with peripheral tumor doses of 10-14 Gy at the 45-70%
      isodoses. No patient developed new facial weakness or sensory loss; 3 patients
      had minor transient facial twitching within a few months of treatment. Of 34
      patients followed more than 1 year (range 14-100 months, mean 43.4 months, median
      37 months), 17 tumors reduced in size, 16 remained unchanged, and 1 increased in
      size. One patient, who had radiosurgery as planned postoperative adjuvant
      treatment after partial resection of a large tumor, developed an enlarging
      peritumoral arachnoid cyst that required surgical resection 79 months after
      radiosurgery. Patients with good pretreatment hearing retained approximately the
      same subjective level of hearing. Very good control of unilateral acoustic
      neuroma has been achieved by a limited-dose scheme that produces minimal
      complications, but due to the frequently indolent course of these tumors,
      continued long-term monitoring will be necessary.

PMID- 15467383
TI  - Effect of carnosine on excitation-contraction coupling in mechanically-skinned
      rat skeletal muscle.
AB  - This study investigated whether carnosine alters individual processes involved in
      normal excitation-contraction (E-C) coupling in mammalian skeletal muscle fibres.
      Mechanically-skinned fibre preparations were utilized because they allow
      carnosine to be precisely and readily applied to the cytoplasmic environment as
      desired, whilst still retaining the normal E-C coupling mechanism. Carnosine
      caused an increase (approximately +0.02 to approximately +0.09 pCa units) in Ca2+
      -sensitivity of the contractile apparatus in a concentration-dependent manner
      (i.e. with 4, 8 and 16 mM respectively). Force responses elicited by 8 mM
      caffeine-induced Ca2+ release from the sarcoplasmic reticulum (SR) were
      potentiated in the presence of carnosine (compared to the bracketing responses in
      the absence of carnosine). Force responses elicited by transverse tubular (T-)
      system depolarization via the dihydropyridine receptors (DHPRs), either by ionic
      (Na+) substitution or by action potentials (APs), were also potentiated in a
      concentration-dependent manner in the presence of carnosine. The potentiation of
      the force responses in all of the various experiments was seemingly totally
      explicable by the increase in Ca2+-sensitivity of the contractile apparatus
      caused by carnosine. Thus, these results show that carnosine potentiates force
      responses solely by 'sensitizing' the contractile apparatus to Ca2+ ions and
      under physiological conditions does not cause additional Ca2+ release from the
      SR.

PMID- 15467384
TI  - How processive is the myosin-V motor?

PMID- 15467385
TI  - Effects of Ca2+ -sensitizers in permeabilized cardiac myocytes from donor and end
      stage failing human hearts.
AB  - During heart failure, alterations occur in contractile protein expression and
      phosphorylation, which may influence the effects of Ca2+ -sensitizers. To
      quantify the magnitude of these effects, isometric force was studied in
      mechanically isolated Triton-skinned myocytes from end-stage failing and non
      failing donor hearts under control conditions (pH 7.2; no added inorganic
      phosphate (Pi)) and under mimicked ischemic conditions (pH 6.5; 10 mM Pi). Two
      different Ca2+ -sensitizers were used: EMD 53998 (10 microM), which exerts its
      influence through the actin-myosin interaction, and OR-1896 (10 microM) (the
      active metabolite of levosimendan), which affects the Ca2+ -sensory function of
      the thin filaments. The maximal force (Po) measured at saturating Ca2+
      concentration and the resting force (Prest) determined in the virtual absence of
      Ca2+ (pCa 9) did not differ between the failing and non-failing myocytes, but the
      Ca2+ concentration required to induce the half-maximal force under control
      conditions was significantly lower in the failing than in the non-failing
      myocytes (DeltapCa50=0.15). This difference in Ca2+ -sensitivity, however, was
      abolished during mimicked ischemia. EMD 53998 increased Po and Prest by
      approximately 15% of Po and greatly enhanced the Ca2+ -sensitivity (DeltapCa50 >
      0.25) of force production. OR-1896 did not affect Po and Prest, and provoked a
      small, but significant Ca2+ -sensitization (DeltapCa50 approximately 0.1). All of
      these effects were comparable in the donor and failing myocytes, but, in contrast
      with OR-1896, EMD 53998 considerably diminished the difference in the Ca2+ 
      sensitivities between the failing and non-failing myocytes. The action of Ca2+ 
      sensitizers under mimicked ischemic conditions was impaired to a similar degree
      in the donor and the failing myocytes. Our results indicate that the Ca2+ 
      activation of the myofibrillar system is altered in end-stage human heart
      failure. This modulates the effects of Ca2+ -sensitizers both under control and
      under mimicked ischemic conditions.

PMID- 15467386
TI  - Stem cells and muscle diseases.
AB  - In the past recent years, basic science work and initial clinical trials have
      provided starting evidence that stem cells are of potential value for treatment
      of certain human diseases, where they could help to regenerate tissues which are
      defective because of either genetic or acquired diseases. This area represents an
      emerging field of biomedicine based on a series of new discoveries in the field
      of stem cell biology and developmental biology that have made possible to isolate
      and expand stem cells from many human tissues. Additional evidence has also
      revealed the role of tissue environment that, by releasing a complex mixture of
      cytokines and growth factors, can influence the recruitment and functional
      integration of stem cells into specific organs. However, there is an urgent need
      for more advancement in basic biology of stem cells and related topics, which
      will be instrumental for the implementation of stem cell-based therapy at the
      clinical level, as treatment accessibility will depend on the acquisition of
      sufficient knowledge to develop adequate technologies to produce sufficient cell
      numbers and to drive their differentiating potentials.

PMID- 15467387
TI  - Muscle plasticity and high throughput gene expression studies.
AB  - Changes in gene expression are known to contribute to muscle plasticity. Until
      recently most studies have described differences of one or few genes at a time,
      in the last few years, however, the development of new technology of high
      throughput mRNA expression analysis has allowed the study of a large part if not
      all transcripts in the same experiment. Knowledge on any muscle adaptive response
      has already gained from the application of this novel approach, but the most
      important new findings have come from studies on muscle atrophy. A new and
      unexpected groups of genes, which increase their expression during atrophy and
      are, therefore, designated as atrogins, have been discovered. In spite of the
      impressive power of the new technology many problems are still to be resolved to
      optimize the experimental design and to extract all information which are
      provided by the outcome of the global mRNA assessment.

PMID- 15467388
TI  - Exercise-modulated mitochondrial phenotype; sensors and gene regulation.

PMID- 15467389
TI  - The role of the calcium channel alpha 2 delta-1 subunit in skeletal muscle.

PMID- 15467390
TI  - Myosin light chain kinase knockout.

PMID- 15467391
TI  - Structure, function and pathology of O-mannosyl glycans.
AB  - Animal cells contain many glycoproteins, i.e. , proteins with covalently liked
      sugar chains. The major glycans of glycoproteins can be classified into two
      groups, N-glycans and O-glycans, according to their glycan-peptide linkage
      regions. Development of sensitive methods for the analyses of glycan structures
      have revealed a new type of glycosidic linkage to the peptide portion, the O
      mannosyl linkage, in mammals, which used to be considered specific to yeast. O
      Mannosylation is present in a limited number of glycoproteins of brain, nerve,
      and skeletal muscle. Recently O-mannosylation has been shown to be important in
      muscle and brain development. Glycobiology of O-mannosyl glycans is expected to
      produce remarkable advances in the understanding and treatment of congenital
      muscular dystrophies. In this article, I describe the structure, biosynthesis,
      and pathology of O-mannosyl glycans.

PMID- 15467392
TI  - Regulation of integrin functions by N-glycans.
AB  - Integrins are cell surface transmembrane glycoproteins that function as adhesion
      receptors in cell-ECM interactions and link matrix proteins to the cytoskeleton.
      Integrins play an important role in cytoskeleton organization and in the
      transduction of intracellular signals, regulating various processes such as
      proliferation, differentiation, apoptosis, and cell migration. Although integrin
      mediated adhesion is based on the binding of alpha and beta subunits to a defined
      peptide sequence, the strength of this binding is modulated by various factors
      including the status of glycosylation of integrin. Glycosylation reactions are
      catalyzed by the catalytic action of glycosyltransferases, such as N
      acetylglucosaminyltransferase III, V and alpha1, 6 fucosyltransferase, etc.,
      which catalyze the formation of glycosidic bonds. This review summarizes effects
      of the posttranslational modification of N-glycans of alpha3beta1 and alpha5beta1
      integrins on their association, activation and biological functions, by using
      biochemical and genetic approaches.

PMID- 15467393
TI  - Construction of a human glycogene library and comprehensive functional analysis.
AB  - Eighteen years have passed after the first mammalian glycosyltransferase was
      cloned. At the beginning of April, 2001, 110 genes for human
      glycosyltransferases, including modifying enzymes for carbohydrate chains such as
      sulfotransferases, had been cloned and analyzed. We started the Glycogene Project
      (GG project) in April 2001, a comprehensive study on human glycogenes with the
      aid of bioinformatic technology. The term glycogene includes the genes for
      glycosyltransferases, sulfotransferases adding sulfate to carbohydrates and sugar
      nucleotide transporters, etc. Firstly, as many novel genes, which are the
      candidates for glycogenes, as possible were searched using bioinformatic
      technology in databases. They were then cloned and expressed in various
      expression systems to detect the activity for carbohydrate synthesis. Their
      substrate specificity was determined using various acceptors.

PMID- 15467394
TI  - Involvement of proteases in glycosyltransferase secretion: Alzheimer's beta
      secretase-dependent cleavage and a following processing by an aminopeptidase.
AB  - Alzheimer's beta-secretase (BACE1) cleaves amyloid precursor protein to produce
      amyloid beta-peptide, which is a crucial initiation process of the pathogenesis
      of Alzheimer's disease. We previously found that BACE1 also cleaves a membrane
      bound sialyltransferase (ST6Gal I). Here we report that, when the protein A
      ST6Gal I fusion protein, or ST6Gal I-derived peptide, was used as an in vitro
      substrate for BACE1, it cleaved the substrates between Leu(37) and Gln(38).
      However, a soluble form of ST6Gal I secreted from COS cells started from Glu(41),
      which was three amino acids shorter than the in vitro product. The results
      suggested that the BACE1 product was truncated by an aminopeptidase(s) before
      secretion. The aminopeptidase activity was successfully detected in detergent
      extracts of Golgi-membrane fraction. Taken together, we concluded that BACE1
      initially cleaved ST6Gal I between Leu(37) and Gln(38), and the NH(2)-terminal
      three amino acids of the yielded product was further trimmed by the
      aminopeptidase.

PMID- 15467395
TI  - The carbohydrate recognition by cytokines modulates their physiological
      activities.
AB  - A variety of cytokines have been reported to be able to recognize specific
      carbohydrate moieties. To date, the role of carbohydrate recognition in cytokine
      function has been analyzed for several cytokines, including fibroblast growth
      factor (FGF), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-2. The FGF
      family and their receptors have been found to recognize a heparan sulfate
      proteoglycan, which generates rigid complexes that induce signal transduction. We
      have found that IL-2 recognizes a high-mannose type glycan on the alpha subunit
      of the IL-2 receptor as well as a peptide portion of this subunit. Blocking this
      carbohydrate-IL-2 interaction diminished IL-2-induced signaling and T-cell
      proliferation. We have also shown that TNF-alpha recognizes the second mannose 6
      phosphate diester of the glycan portion of glycosylphosphatidylinositol (GPI)
      anchored glycoproteins. Blocking this GPI-anchored glycan-TNF-alpha interaction
      abrogates TNF-alpha-induced apoptosis. We aim to increase the number of cytokines
      which modulate their functions through the unique carbohydrate recognition, and
      open the way to systematically elucidate the biological functions of cytokine
      carbohydrate interaction in immune system.

PMID- 15467396
TI  - Lectin-based structural glycomics: glycoproteomics and glycan profiling.
AB  - Structural glycomics (SG) plays a fundamental part of concurrent glycobiology
      aiming at comprehensive elucidation of glycan functions ( i.e. , functional
      glycomics) in the context of post-genome sciences. The SG project started in
      April 2003 and will continue for 3 years in the framework of NEDO (New Energy and
      Industrial Technology Organization) under the METI (the Ministry of Economy,
      Trade, and Industry), Japan. The main purpose of the project is the development
      of high-throughput and robust machines, which should greatly contribute to the
      structural analysis of complex glycans. In this chapter, 2 major research items,
      i.e. , (1) glycoproteomics, which enables comprehensive analysis of
      glycoproteins, and (2) "glycan profiling" by means of lectins, are described. For
      the latter, frontal affinity chromatography has been adopted as a starting tool
      for comprehensive analysis of the interaction of 100 lectins and 100
      oligosaccharides under the concept of "hect-by-hect," which refers to 100 x 100.

PMID- 15467397
TI  - Carbohydrate antigens expressed on stem cells and early embryonic cells.
AB  - Lewis X antigen (Le(X)) is a marker of embryonic stem cells, embryonal carcinoma
      cells and multipotential cells of early embryos in the mouse. Le(X) is carried by
      branched, high-molecular weight poly-N-acetyllactosamines (embryoglycan). While
      embryoglycan is present in human embryonal carcinoma cells, Le(X) is not
      expressed in human embryonic stem cells, embryonal carcinoma cells or inner cell
      mass cells. Instead, these cells express SSEA-3 and SSEA-4, both of which are
      carried by globo-series glycolipids. Le(X) is a marker of primordial germ cells
      or multipotential stem cells derived from primordial germ cells both in the mouse
      and human. In other species of vertebrates, Le(X) is widely expressed in early
      embryonic cells and primordial germ cells, but the mode of expression is not
      completely conserved among species. Le(X) is expressed in neural stem cells from
      both humans and mice. Hematopoietic stem cells are not reported to express the
      above carbohydrate markers. A marker of these cells is CD34, a membrane-bound
      sialomucin. Another sialomucin, CD164 (MGC-24v) is expressed in hemotopoietic
      progenitor cells. As a function of Le(X) in stem cells, the promotion of integrin
      action is proposed, based on analyses of glycoproteins with the marker, cDNA
      transfection experiments and the inhibitory effects of an anti-Le(X) antibody.
      Most probably, Le(X) antigen as well as poly-N-acetyllactosamines play roles in
      the interactions on the same membrane. On the other hand, O-linked
      oligosaccharides on CD34 and CD164 are probably involved in the regulation of
      cell adhesion and proliferation via intercellular recognition.

PMID- 15467399
TI  - Neuroglycan C, a brain-specific part-time proteoglycan, with a particular
      multidomain structure.
AB  - Neuroglycan C (NGC) is a transmembrane-type of chondroitin sulfate proteoglycan
      that is exclusively expressed in the central nervous system. NGC gene expression
      is developmentally regulated, and is altered by addiction to psychostimulants and
      by nerve lesion. Its core protein has a particular multidomain structure
      differing from those of other known proteoglycans, and this protein is modified
      post-translationally in various ways such as phosphorylation and glycosylation.
      NGC is a novel part-time proteoglycan that changes its structure from a
      proteoglycan form to a non-proteoglycan form without chondroitin sulfate chains
      during the development of the cerebellum and retina. Results obtained from
      immunohistological, cell biological and biochemical experiments suggest that NGC
      is involved in neuronal circuit formation in the central nervous system. To
      verify the proposed functions of NGC in the brain, production and phenotype
      analyses are being performed in mice with various NGC gene mutations causing the
      expression or glycosylation of NGC to be altered.

PMID- 15467398
TI  - Sulfation pattern in glycosaminoglycan: does it have a code?
AB  - Heparan sulfate chains (HS) are initially synthesized on core proteins as linear
      polysaccharides composed of glucuronic acid--N-acetylglucosamine repeating units
      and subjected to marked structural modification by sulfation (N-, 2-O-, 6-O-, 3-O
      sulfotransferases) and epimerization (C5-epimerase) at the Golgi lumen and
      further by desulfation (6-O- endosulfatase) at the cell surface, after which
      divergent fine structures are generated. The expression patterns and specificity
      of the modifying enzymes are, at least partly, responsible for the elaboration of
      these fine structures of heparan sulfate. HS interacts with many proteins
      including growth factors (GF) and morphogens through specific fine structures.
      Recent biochemical and genetic studies have presented evidence that HS plays
      important roles in cell behavior and organogenesis. In knock-down experiments of
      heparan sulfate 6-O-sulfotransferase, 6-O-sulfated units in HS have been shown to
      act as a stimulator or suppressor according to individual GF/morphogen signaling
      systems.

PMID- 15467400
TI  - Biological roles of sulfoglycolipids and pathophysiology of their deficiency.
AB  - Mammalian sulfoglycolipids are comprised of two major members, sulfatide (SO(3)
      3Gal-ceramide) and seminolipid (SO(3)-3Gal-alkylacylglycerol). Sulfatide is
      abundant in the myelin sheath and seminolipid is expressed on the spermatogenic
      cells. Cerebroside sulfotransferase (CST)-deficient mice generated by gene
      targeting completely lack sulfatide and seminolipid all over the body. CST-null
      mice manifest some neurological disorders due to myelin dysfunction, an aberrant
      enhancement of oligodendrocyte terminal differentiation, and an arrest of
      spermatogenesis, indicating that sulfation of glycolipids is essential for myelin
      formation and spermatogenesis. Moreover, CST-deficiency ameliorates L-selectin
      dependent monocyte infiltration in the kidney after ureteral obstruction, an
      experimental model of renal interstitial inflammation, indicating that sulfatide
      is an endogenous ligand of L-selectin. Studies on the molecular mechanisms by
      which sulfoglycolipids participate in these biological processes are ongoing.

PMID- 15467401
TI  - Approach for functional analysis of glycan using RNA interference.
AB  - The elucidation of the biological role of glycan is one of the most important
      issues to be resolved following the genome project. RNA interference is becoming
      an efficient reverse genetic tool for studying gene function in model organisms,
      including C.elegans and Drosophila melanogaster. Our molecular evolutionary study
      has shown that a prototype of glycosyltransferases, which synthesize a variety of
      glycan structures in the Golgi apparatus, was conserved between mammals and
      Drosophila. For analyses of the basic physiological functions of glycans, we
      established the Drosophila inducible RNAi knockdown system and applied it to one
      glycosyltransferase and one transporter, proteoglycan UDP-galactose: beta-xylose
      beta1,4galactosyltransferase I and the PAPS-transporter, respectively. If on the
      silencing of each gene induced ubiquitously under the control of a cytoplasmic
      actin promoter, the RNAi knockdown fly died, then the protein was indispensable
      for life. The expression of the target gene was disrupted specifically and the
      degree of interference was well correlated with the phenotype. The inducible RNAi
      knockdown fly obtained using the GAL4-UAS system will pave the way for the
      functional analysis of glycans.

PMID- 15467402
TI  - Synthesis of glycoprotein molecular probes for the analyses of protein quality
      control system.

PMID- 15467403
TI  - Expression of human glycosyltransferase genes in yeast as a tool for enzymatic
      synthesis of sugar chain.
AB  - We planned the production of human glycosyltransferases in yeast for the
      enzymatic synthesis of various sugar chains. More than 160 genes encoding various
      glycosyltransferases were prepared as N-terminal transmembrane region truncated
      forms by PCR and were inserted into the entry vector of Invitrogen Ltd's Gateway
      system. About fifty glycosyltransferases were chosen for the synthesis of human
      type oligosaccharides, and expressed as two different forms in yeast. One is a
      soluble form, which is secreted into the culture medium by methylotrophic yeast,
      and the other is an immobilized form, which is displayed at the budding yeast
      cell wall as a fusion protein with Pir protein. To date, in both systems, some
      sialyltranferases and fucosyltransferases have been produced as active forms,
      indicating the potential usefulness of these systems for the enzymatic synthesis
      of various types of human sugar chains attached to proteins and lipids.

PMID- 15467405
TI  - The effect of state laws on the supply of advanced practice nurses.
AB  - This paper considers how the decision to enter advanced practice nursing (e.g.,
      the occupations of nurse practitioner, certified nurse-midwife, nurse
      anesthetist, and clinical nurse specialist) is affected by State laws on the
      scope of practice of APNs. We find that enrollments in APN programs are 30
      percent higher in States where APNs have a high level of professional
      independence. Our work differs from previous studies by estimating a fixed
      effects model on cross-sectional and time series data, to avoid problems of
      endogeneity of State laws.

PMID- 15467404
TI  - Superoxide production from human polymorphonuclear leukocytes by human mannan
      binding protein (MBP).
AB  - Mannan-binding protein (MBP) is a Ca(2+)-dependent mammalian lectin that plays an
      important role in innate immunity. In this study, we found that ligand-bound MBP
      stimulates polymorphonuclear leukocytes (PMN) to induce cell aggregation and
      superoxide production. The biological response of PMN to ligand-bound MBP was
      dose- and time-dependent. The PMN aggregation and superoxide production induced
      by ligand-bound MBP was blocked completely by pertussis toxin, and partially
      blocked by a platelet activation factor receptor antagonist, TCV-309. These
      findings suggest that the ligand-bound MBP stimulates PMN through a putative MBP
      receptor(s) on PMN.

PMID- 15467406
TI  - Deductibles and health care expenditures: empirical estimates of price
      sensitivity based on administrative data.
AB  - OBJECTIVE: To estimate the price sensitivity of demand for health care by
      analysing the relation between deductibles and expenditures found in an
      administrative database. DATA: Data are from 100,048 privately insured in the
      Netherlands. Information is available on expenditures in 1996, demographic
      variables, deductibles, and both diagnoses from hospitalisations and pharmacy
      costs for the years 1993-1995. The data are unique because prior pharmacy costs
      are good predictors of future expenditures while in the three years concerned
      these costs were covered by a separate national, mandatory insurance scheme.
      Therefore, these costs are not affected by deductibles and can be seen as
      excellent proxies for health status, which this study uses to correct for the
      existing adverse selection with respect to the choice of deductible. METHODS: For
      the group of insured without deductibles an expenditure model is estimated which
      is subsequently used to estimate expected expenditures for insurance policies
      with various levels of deductible. From the difference between actual and
      expected expenditures the impact of deductibles on expenditures is estimated, and
      from this price sensitivity. RESULTS: The principal finding is an estimated price
      elasticity of -0.14. The highest price sensitivity is found for GP care (-0.40)
      and physiotherapy (-0.32), and the lowest for specialist care (-0.12) and
      prescription drugs (-0.08); hospital care was hardly affected.

PMID- 15467407
TI  - How did dentists respond to the introduction of global budgets in Taiwan? An
      evaluation using individual panel data.
AB  - In response to the introduction of global budgets, dentists might alter their
      supply behaviour, changing the number of visits, the amount of expenditure, and
      the type of services provided. We develop two-way fixed effects models to
      estimate these effects using a panel data constructed from outpatient dental care
      expenditures claims from the Taiwanese National Health Insurance system. The
      availability of a long panel allows us to estimate a "policy effect" for each
      dentist in the panel. The overall effect of global budgets is to constrain costs
      but there is evidence of a change in the mix of services. Male and younger
      dentists have higher policy effects than female and older dentists. Global
      budgets favour dentists in deprived areas and there is some evidence of increases
      in the expenditure per visit and the volume of composite resin fillings.

PMID- 15467408
TI  - The impact of ownership conversions on HMO performance.
AB  - Recently, several Blue Cross plans that sponsor Health Maintenance Organizations
      (HMOs), among other insurance products, have sought regulatory approval to
      convert from a not-for-profit to a for-profit entity. We examine the impact of
      not-for-profit HMOs converting to for-profit status in a fixed-effects framework
      using HMO level data from InterStudy. Our findings indicate conversions to for
      profit status do not significantly impact HMO prices, profit margins, use of
      hospital days or ambulatory visits, and the provision of Medicare and Medicaid
      products.

PMID- 15467409
TI  - Hospital competition under regulated prices: application to urban health sector
      reforms in China.
AB  - We develop a model of public-private hospital competition under regulated prices,
      recognizing that hospitals are multi-service firms and that equilibria depend on
      the interactions of patients, hospital administrators, and physicians. We then
      use data from China to calibrate a simulation model of the impact of China's
      recent payment and organizational reforms on cost, quality and access. Both the
      analytic and simulation results show how providing implicit insurance through
      distorted prices leads to over/under use of services by profitability, which in
      turn fuels cost escalation and reduces access for those who cannot afford to self
      pay for care. Simulations reveal the benefits of mixed payment and expanded
      insurance cover for mitigating these distortions.

PMID- 15467410
TI  - Perfusion imaging of the brain using Z-score and dynamic images obtained by
      subtracting images from before and after contrast injection.
AB  - OBJECTIVE: The aim of this study was to examine the feasibility of perfusion
      imaging of the brain using the Z-score and subtraction dynamic images obtained
      from susceptibility contrast MR images. MATERIALS AND METHODS: Five patients,
      each with a normal MRI, Moya-moya, a middle cerebral artery occlusion, post
      trauma syndrome, and a metastatic brain tumor, were selected for a presentation.
      A susceptibility-contrast echo-planar image after a routine MRI was taken as the
      source image with a rapid manual injection of 0.1 mmol/kg of Gd-DTPA. The inflow
      and washout patterns were observed from the time-signal intensity curve of the
      serial scans using the standard program of an MRI machine. The repeated Z-score
      images of the peak and late phases were made using the threshold Z-score values
      between 1.4 and 2.0 in four to five studies of the pre-contrast, peak, and late
      phases. Dynamic subtraction images were produced by subtracting sequential post
      contrast images from a pre-contrast image and coloring these images using a
      pseudocolor mapping method. RESULTS: In the diseases with perfusion
      abnormalities, the Z-score images revealed information about the degree of
      perfusion during the peak and late phases. However, the quality varied with the Z
      score threshold and the studies selected in a group. The dynamic subtraction
      images were of sufficient quality with no background noise and more clearly
      illustrated the temporal changes in perfusion and delayed perfusion. CONCLUSION:
      The Z-scores and dynamic subtraction images illustrated the degree of perfusion
      and sequential changes in the pattern of perfusion, respectively. These images
      can be used as a new complimentary method for observing the perfusion patterns in
      brain diseases.

PMID- 15467411
TI  - Hepatopulmonary syndrome induced by common bile duct ligation in a rabbit model:
      correlation between pulmonary vascular dilatation on thin-section CT and
      angiography and serum nitrite concentration or endothelial nitric oxide synthase
      (eNOS)1 expression.
AB  - OBJECTIVE: To investigate the correlation between radiologic vascular dilatation
      and serum nitrite concentration and eNOS expression in the endothelial cell and
      pneumocyte in a rabbit model of hepatopulmonary syndrome induced by common bile
      duct ligation (CBDL). MATERIALS AND METHODS: Thin-section CT scans of the lung
      and pulmonary angiography were obtained 3 weeks after CBDL (n = 6), or a sham
      operation (n = 4), and intrapulmonary vasodilatation was assessed. The diameter
      and tortuosity of peripheral vessels in the right lower lobe by thin-section CT
      and angiography at the same level of the right lower lobe in all subjects were
      correlated to serum nitrite concentration and eNOS (endothelial nitric oxide
      synthase) expression as determined by immunostaining. RESULTS: The diameters of
      pulmonary vessels on thin-section CT were well correlated with nitrite
      concentrations in serum (r = 0.92, p < 0.001). Dilated pulmonary vessels were
      significantly correlated with an increased eNOS expression (r = 0.94, p <
      0.0001), and the severity of pulmonary vessel tortuosity was found to be well
      correlated with serum nitrite concentration (r = 0.90, p < 0.001). CONCLUSION:
      The peripheral pulmonary vasculature in hepatopulmonary syndrome induced by CBLD
      was dilated on thin-section CT and on angiographs. Our findings suggest that
      peripheral pulmonary vascular dilatations are correlated with serum nitrite
      concentrations and pulmonary eNOS expression.

PMID- 15467412
TI  - Cystic changes in intraabdominal extrahepatic metastases from gastrointestinal
      stromal tumors treated with imatinib.
AB  - OBJECTIVE: This study was undertaken for the purpose of describing the CT
      features of intra-abdominal extra-hepatic metastases from gastrointestinal
      stromal tumors in patients who were treated with imatinib. MATERIALS AND METHODS:
      Eleven patients with intra-abdominal extra-hepatic metastases from
      gastrointestinal stromal tumors, who were treated with imatinib between May 2001
      and December 2003, were included in this study. The clinical findings and CT
      scans were retrospectively reviewed. The metastatic lesions were assessed
      according to the location, size (greatest diameter), attenuation, and the
      enhancing pattern before and after imatinib treatment. RESULTS: Prior to the
      treatment, the sizes and attenuation values of the metastatic lesions ranged from
      5 to 20 cm and from 63 to 131 H, respectively. The metastatic lesions showed a
      heterogeneous enhancement pattern on the contrast-enhanced CT scans. After the
      treatment, the metastatic lesions became smaller in all 11 patients, and the
      corresponding attenuation value ranged from 15 to 51 H. The metastatic lesions
      became homogeneous and cystic in appearance on the follow-up CT scans, mimicking
      ascites. CONCLUSION: Intra-abdominal extra-hepatic metastases of patients with
      gastrointestinal stromal tumors treated with imatinib may appear as well
      circumscribed cystic lesions on contrast-enhanced CT. These metastases are likely
      to become smaller and resemble ascites, but may persist indefinitely on the
      followup CT.

PMID- 15467413
TI  - Causes of arterial bleeding after living donor liver transplantation and the
      results of transcatheter arterial embolization.
AB  - OBJECTIVE: To analyze the causes of arterial bleeding after living donor liver
      transplantation (LDLT) and to evaluate the efficacy of transcatheter arterial
      embolization (TAE). MATERIALS AND METHODS: Forty-two sessions of conventional
      arteriography were performed in 32 of the 195 patients who underwent LDLT during
      the past 2 years. This was done in search of bleeding foci of arterial origin.
      TAE was performed with microcoils or gelatin sponge particles. The causes of
      arterial bleeding, the technical and clinical success rates of TAE and the
      complications were retrospectively evaluated. RESULT: Forty-two bleeding foci of
      arterial origin were identified on 30 sessions of arteriography in 21 patients.
      The most common cause of bleeding was percutaneous procedures in 40% of the
      patients (17 of the 42 bleeding foci) followed by surgical procedures in 36%
      (15/42). The overall technical and clinical success rates of TAE were 21 (70%)
      and 20 (67%) of the 30 sessions, respectively. The overall technical success rate
      of TAE for the treatment of bleeding from the hepatic resection margin, hepatic
      artery anastomotic site and hepaticojejunostomy was only 18% (2/11), whereas for
      the treatment of bleeding in the other locations the technical and clinical
      success rates of TAE were 100% and 95%, respectively. No procedure-related major
      complications occurred. CONCLUSION: In the case of arterial bleeding after LDLT,
      percutaneous procedure-related hemorrhages were as common as surgery-related
      hemorrhages. There were technical difficulties in using TAE for the treatment of
      hepatic arterial bleeding. However, in the other locations, TAE seems to be safe
      and effective for the control of arterial bleeding in LDLT recipients.

PMID- 15467414
TI  - Acute necrotizing encephalopathy in Korean infants and children: imaging findings
      and diverse clinical outcome.
AB  - OBJECTIVE: The purpose of our study was to describe acute necrotizing
      encephalopathy in Korean infants and children, and we sought to evaluate the
      prognostic factors. MATERIALS AND METHODS: Acute necrotizing encephalopathy was
      diagnosed in 14 Korean infants and children. We retrospectively analyzed the
      neuroimaging findings including the follow-up changes. The clinical course of the
      disease was graded, and we evaluated prognostic factors including age, serum
      level of the aminotransferase, hemorrhage, and localized atrophy of the brain.
      RESULT: This encephalopathy predominantly affected the bilateral thalami (n =
      14), pons (n = 12), and midbrain (n = 10) in a symmetrical pattern. Hemorrhage
      was observed in eight patients (57%). On the follow-up images (n = 12), the brain
      lesions were reduced in extent for all patients, and generalized atrophy was seen
      in six patients. Localized tissue loss was observed in five patients and a
      complete resolution occurred for one patient. All the patients survived and two
      recovered completely; mild (n = 6) to severe (n = 6) neurological deficits
      persisted in the remaining 12 patients. The significant prognostic factors
      identified in this study were the presence of hemorrhage (p = 0.009) and
      localized atrophy (p = 0.015). CONCLUSION: Acute necrotizing encephalopathy in
      Korean patients showed the characteristic patterns of the post-infectious
      encephalopathy as described in the literature. The high survival rate and the
      relatively favorable clinical course observed for the present study suggest a
      more diverse spectrum of disease severity than was previously described. The
      presence of hemorrhage and localized tissue loss on MR images may suggest a poor
      prognosis.

PMID- 15467415
TI  - US features of transient small bowel intussusception in pediatric patients.
AB  - OBJECTIVE: To describe the sonographic (US) and clinical features of
      spontaneously reduced small bowel intussusception, and to discuss the management
      options for small bowel intussusception based on US findings with clinical
      correlation. MATERIALS AND METHODS: During a five years of period, 34 small bowel
      intussusceptions were diagnosed on US in 32 infants and children. The clinical
      presentations and imaging findings of the patients were reviewed. RESULTS: The
      clinical presentations included abdominal pain or irritability (n = 25), vomiting
      (n = 5), diarrhea (n = 3), bloody stool (n = 1), and abdominal distension (n =
      1), in combination or alone. US showed multi-layered round masses of small (mean,
      1.5+/-0.3 cm) diameters and with thin (mean, 3.5+/-1 mm) outer rims along the
      course of the small bowel. The mean length was 1.8+/-0.5 cm and peristalsis was
      seen on the video records. There were no visible lead points. The vascular flow
      signal appeared on color Doppler images in all 21 patients examined. Spontaneous
      reduction was confirmed by combinations of US (n = 28), small bowel series (n =
      6), CT scan (n = 3), and surgical exploration (n = 2). All patients discharged
      with improved condition. CONCLUSION: Typical US findings of the transient small
      bowel intussusception included 1) small size without wall swelling, 2) short
      segment, 3) preserved wall motion, and 4) absence of the lead point. Conservative
      management with US monitoring rather than an immediate operation is recommended
      for those patient with typical transient small bowel intussusceptions. Atypical
      US findings or clinical deterioration of the patient with persistent
      intussusception warrant surgical exploration.

PMID- 15467416
TI  - Radiofrequency ablation of liver cancer: early evaluation of therapeutic response
      with contrast-enhanced ultrasonography.
AB  - The early assessment of the therapeutic response after percutaneous
      radiofrequency (RF) ablation is important, in order to correctly decide whether
      further treatment is necessary. The residual unablated tumor is usually depicted
      on contrast-enhanced multiphase helical computed tomography (CT) as a focal
      enhancing structure during the arterial and portal venous phases. Contrast
      enhanced color Doppler and power Doppler ultrasonography (US) have also been used
      to detect residual tumors. Contrast-enhanced gray-scale US, using a harmonic
      technology which has recently been introduced, allows for the detection of
      residual tumors after ablation, without any of the blooming or motion artifacts
      usually seen on contrast-enhanced color or power Doppler US. Based on our
      experience and reports in the literature, we consider that contrast-enhanced gray
      scale harmonic US constitutes a reliable alternative to contrast-enhanced
      multiphase CT for the early evaluation of the therapeutic response to RF ablation
      for liver cancer. This technique was also useful in targeting any residual
      unablated tumors encountered during additional ablation.

PMID- 15467417
TI  - Multi-slice spiral CT of living-related liver transplantation in children:
      pictorial essay.
AB  - In pediatric living-related liver transplantation, preoperative evaluation of the
      recipient is important for surgical planning, while the accurate diagnosis of
      postoperative complications is essential for graft salvage. Multiplanar and three
      dimensional imaging using multi-slice spiral CT can be used for preoperative
      vascular imaging, as well as for evaluating postoperative complications. In this
      essay, we describe the usefulness of multi-slice CT, combined with a variety of
      different reconstruction techniques, for the preoperative evaluation of
      transplant recipients. In addition, we demonstrate the multi-slice CT findings of
      postoperative complications, including vascular stenosis or thrombosis, bile duct
      leak or stricture, and extrahepatic fluid collection.

PMID- 15467418
TI  - Fish bone as a nidus for stone formation in the common bile duct: report of two
      cases.
AB  - We report two cases of common bile duct stone formed around a fish bone which
      migrated from the intestinal tract, along with their characteristic imaging
      findings. Two patients who had no history of previous operation were admitted
      because of cholangitis. Percutaneous transhepatic biliary drainage (PTBD) was
      performed and the cholangiogram showed filling defects with an unusually
      elongated shape in the common bile duct. After improvement of the cholangitic
      symptoms, the stones were removed through the PTBD tract under fluoroscopic
      guidance. A nidus consisting of a 1.5 cm sized fish bone was found in each stone
      removed.

PMID- 15467419
TI  - High grade hemangioendothelioma of the temporal bone in a child: a case report.
AB  - Hemangioendothelioma is a rare vascular tumor characterized by endothelial tumor
      cells and variable malignant behavior, and it's not common for this lesion to
      involve the bone. Although there are a few reports of cranial involvement by
      hemangioendothelioma, only rare cases arising in temporal bone have been
      published. We present the radiologic findings of a 7-year-old boy who had a high
      grade hemangioendothelioma involving the temporal bone with intracranial
      extension. Evidence of flow voids on MR images suggested a tumor of vascular
      origin, and the ill-defined margins, cortical destruction and intracranial
      extension on the CT and MR images were correlated with the tumor's high
      histologic grade.

PMID- 15467420
TI  - Do elevated levels of eicosanoids play a role in head and neck cancer recurrence
      and metastasis? Implications for prevention and treatment.

PMID- 15467422
TI  - Could labeled neuronal progenitor cells be used to target glioma tumor
      endothelium?

PMID- 15467421
TI  - Altered epigenetic signals in human disease.
AB  - The genetic information of almost all eukaryotic cells is stored in chromatin. In
      cancer cells, alterations in chromatin organization or in its epigenetic marks
      occur frequently. Among these are changes in the patterns of DNA and histone
      methylation. Using Acute Promyelocytic Leukemia as model system we could
      demonstrate a direct correlation of epigenetic events induced by the driving
      oncogene product PML-RARalpha and cancer progression. Several of the enzymes
      ultimately responsible for these events can be inhibited by small compound
      inhibitors and thus can serve as targets in cancer therapy. In this article, we
      review the role of DNA methylation, histone methylation and chromatin alterations
      in human diseases. A picture is emerging in which these epigenetic signals "cross
      talk" and are implicated in the physiological and pathological spreading of gene
      silencing.

PMID- 15467423
TI  - Shifting paradigms in hormonal therapy for breast cancer.
AB  - BACKGROUND: Tamoxifen has been the mainstay of endocrine treatment for
      postmenopausal patients with early and advanced breast cancer for many years.
      However, as an anti-estrogen with partial estrogenic effects, tamoxifen also has
      some serious safety and tolerability issues. Following tamoxifen treatment
      failure there were initially limited options for subsequent therapy. Therefore,
      new agents, including new anti-estrogens and aromatase inhibitors (AIs) were
      developed. METHODS: Data for this review were identified by searches of PubMed
      and references from relevant articles. Abstracts were included only when the
      relevant information had not been published in full elsewhere. Only papers
      published in English were included. RESULTS: The AIs have been shown to be
      effective treatments for hormone-sensitive metastatic breast cancer. CONCLUSIONS:
      Current clinical trial data in early breast cancer show longer disease-free
      survival and time to recurrence with anastrozole than that demonstrated with
      tamoxifen and very good general tolerability, although longer follow-up is
      warranted. Clinical trials of the use of AIs in breast cancer prevention and
      preliminary data for the combination of anastrozole with a gonadotrophin
      releasing hormone for the treatment of premenopausal women with early stage
      breast cancer are also discussed here.

PMID- 15467424
TI  - Resveratrol: a whiff that induces a biologically specific tsunami.

PMID- 15467425
TI  - Hydrodynamic consequences of glycolysis: thermodynamic basis and clinical
      relevance.
AB  - Since Warburg's original description of aerobic and anaerobic glycolysis in 1924,
      the biochemical and molecular bases of glucose metabolism in cells have been
      characterized. However, its thermodynamic implications have found little
      attention. Van't Hoff's law of thermodynamics was applied here to describe how
      glucose metabolism affects intracellular osmotic pressure, hence revealing how
      glucose metabolism provides cells with osmotic energy as well as chemical energy.
      Ensuing osmosis-driven movement of free water across membranes affects cell
      volume and shape, hydration of intracellular components, and interactions of
      cells with their environment. Comparative analysis of extant data revealed strong
      evidence for clinically relevant glycolysis-driven effects under hypoxic
      conditions known to occur in cancer, vascular disease as well as intensive care,
      including critical and preventable ones affecting treatment effectiveness and
      thus, clinical outcome. These findings provide the first evidence confirming the
      existence of glycolysis-driven hydrodynamic effects and suggest that high levels
      of aerobic and anaerobic glycolysis provide a common biophysical basis in
      seemingly unrelated medical conditions.

PMID- 15467426
TI  - Perspectives of SEREX-defined antigens in diagnosis and immunotherapy for gastric
      cancer.
AB  - Gastric cancer is the most common malignancy in the world. Often diagnosed at
      advanced and unresectable stage, there is no curative treatment available for
      gastric cancer. Immunotherapy might be a promising alternative option. The key
      challenge in gastric cancer diagnosis and immunotherapy is to find an efficient
      target that not only provide early indication of the disease but also can
      upregulate the anti-tumor immune response in the cancer patients. Tumor
      associated antigens(TAAs) expressed in tumor cells can elicit the immune response
      in autologous host and are related to changes during the disease process may
      fulfill this demanding. Now, Thousands of antigens have been discovered by a
      powerful method called SEREX(serological analysis of tumor antigen by recombinant
      cDNA expression libraries) and some of SEREX-defined antigens have been evaluated
      in clinical trails as vaccines for cancer immunotherapy. This review will provide
      information on the application of SEREX method in gastric cancer research and
      knowledge learned from these studies to develop antigen-specific diagnosis and
      therapy for gastric cancer.

PMID- 15467427
TI  - Expression analysis of the epigenetic methyltransferases and methyl-CpG binding
      protein families in the normal B-cell and B-cell chronic lymphocytic leukemia
      (CLL).
AB  - The importance of epigenetic modifications in carcinogenesis has been a source of
      controversy for some time. There is little doubt that changes in genomic
      hypermethylation contribute to the silencing of tumor suppressor genes.
      Furthermore, recent studies have also identified the significance of genomic
      hypomethylation associated with chromosomal instability and tumorigenesis. One of
      the most perplexing questions regarding epigenetic modifications and
      leukemogenesis is the relationship with DNA methyltransferases (DNMT's). The
      primary function of the DNMT enzymes is to methylate genomic DNA, whereas the
      methyl-CpG binding domain proteins (MBD) interpret this methylation signal and
      regulate gene expression and chromatin behavior. In this study we analyse these
      gene families by quantitative real-time PCR to investigate whether expression
      levels and the B-cell chronic lymphocytic leukemia (B-CLL) phenotype are
      associated. Furthermore, given the epigenetic crosstalk between genome stability
      and the histone chromatin code we have analysed eukaryotic histone
      methyltransferase (Eu-HMTaseI). Surprisingly, we did not observe significant
      changes in DNMT1 expression in B-CLL cases when compared to normal lymphocytes,
      regardless of whether we normalise against GAPDH or PCNA as reference standards.
      Indeed, expression of the maintenance and de novo methylases were independently
      regulated. Of particular note was the significant down regulation of DNMT3b.
      Furthermore, we observed a positive correlation between HMTaseI expression levels
      and stage of leukemia suggesting that changes in the methylation patterns in B
      CLL may represent deregulation of the epigenetic repertoire that also include the
      methylation dependent binding proteins, MBD2 and MeCP2. We envisage changes in
      the epigenetic program are multifactorial in nature and postulate that the
      prevalent genomic methylases just one component of a larger epigenetic
      repertoire.

PMID- 15467428
TI  - Alterations of p53, Bcl-2, and hMSH2 protein expression in the normal breast,
      benign proliferative breast disease, in situ and infiltrating ductal breast
      carcinomas in the upper Egypt.
AB  - BACKGROUND: Tumorigenesis involves alterations in the tumor suppressor genes
      (p53), protooncogenes (Bcl-2) and housekeeping genes [human MutS homologue-2
      (hMSH2)]. We hypothesized that mammary carcinogenesis involves interactions among
      p53, Bcl-2 and hMSh2 proteins. In the Upper Egypt, the clinicopathologic features
      and genetic changes during mammary carcinogenesis are unknown. METHODS: To test
      our hypothesis and to examine these issues, 53 mastectomy specimens, each
      entailing normal breast, benign proliferative breast disease (BPBD), duct
      carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) were
      immunostained for p53, Bcl-2 and hMSH2 protein expression. RESULTS: The average
      age incidence of ductal carcinomas was 43.2 +/- 7.06 years. The tumors were
      common in the left than right side (1.2:1, respectively, p > 0.05). Infiltrating
      ductal carcinoma of non-specific type was the most common histologic type.
      Examination of the average weighted scores in the normal breast, BPBD, DCIS and
      IDC, respectively, showed: (1) significant upregulation of p53 proteins (0.00 +/-
      0.00, 0.00 +/- 0.00, 6.25 +/- 2.42, 6.62 +/- 2.15, p = 0.001), (2) insignificant
      downregulation of Bcl-2 (6.67 +/- 1.33, 5.17 +/- 2.20, 4.79 +/- 2.27 and 4.42 +/-
      2.83, p = 0.37), and (3) significant downregulation of hMSH2 (11.3 +/- 0.75,
      10.70 +/- 1.27, 7.11 +/- 1.50 and 7.0 +/- 1.33, p = 0.0006). There were
      insignificant negative correlations between p53 and both Bcl-2 (r = -0.20, p >
      0.05) and hMSH2 (r = -0.15, p > 0.05) protein expression. CONCLUSIONS: In the
      Upper Egypt: (1) breast cancer had similar clinicopathologic features to those in
      the high risk regions, and (2) alterations of the p53, Bcl-2 and hMSH2 proteins
      occur during mammary carcinogenesis.

PMID- 15467429
TI  - 99mTc-Tetraethylenepentamine-Folate--a new 99mTc-based folate derivative for the
      detection of folate receptor positive tumors: synthesis and biological
      evaluation.
AB  - A new radiopharmaceutical, 99mTc-Tetraethylenepentamine(TEPA)-Folate has been
      synthesized introducing TEPA to the gamma-carboxyl group of folic acid. This
      binds with 99mTc high efficiency at ambient temperature. The resulting 99mTc-N5
      Folate is stable under physiological conditions at least for 24 h after
      radiocomplexation. TEPA is a known open chain pentamine (N5) chelator, its four
      nitrogen act as the binding site for 99mTc. The folate membrane receptor binding
      of the 99mTc-TEPA-Folate by established human tumor cell lines (KB, U-87MG and
      MDA-MB-468) showed Kd in microM range in normal DMEM (10% serum, 10 microM folic
      acid). The blood kinetic studies showed more than 70% clearance within five
      minutes from the circulation. The KB cell line tumors in mice were readily
      identifiable in the gamma images and revealed major accumulation of radiotracer
      in liver, kidneys and intestines. High tumor uptake was shown in the tumor
      bearing nude mice; tumorto-blood ratios reached 2.68 +/- 0.52 and 5.5 +/- 1.47 at
      1 and 4 h after post injection respectively. Surviving fractions as obtained in
      clonogenic assay were 1.02 +/- 0.07 and 1.03 +/- 0.05 in U-87MG and MDA-MB-468
      cell lines respectively. The 99mTc-N5-Folate conjugate have promising utility as
      a receptor specific radiopharmaceutical for imaging neoplastic tissues known to
      over express folate-binding protein.

PMID- 15467430
TI  - Anomalous expression of the HLA-DR alpha and beta chains in ovarian and other
      cancers.
AB  - Tumor formation in immunocompetent hosts is believed to be dependent on the
      ability of tumor cells to evade the immune system, as suggested by the
      alterations of expression of the major histocompatibility complex (MHC) and
      related molecules in a number of cancers. Our previous serial analysis of gene
      expression (SAGE) study revealed that HLA-DRA (encoding the alpha chain of HLA
      DR) is one of the most highly overexpressed genes in ovarian cancer. This finding
      was unanticipated, as overexpression of MHC molecules would be expected to
      increase tumor immunogenicity, therefore compromising tumor growth. We have now
      examined the expression of HLA-DR alpha chain in ovarian and a variety of other
      cancers using tissue arrays and found it overexpressed in a majority of the
      cancer tissues investigated. In contrast, the HLA-DR beta chain, which together
      with the alpha chain forms the functional HLA-DR complex, was not frequently
      found expressed in cancer, resulting to a lack of mature HLA-DR in these tissues.
      Interestingly, HLADRA and HLADRB transcripts were both found expressed in many
      other cancer types, including ovarian cancer, suggesting that the downregulation
      of HLADR beta chain is a post-transcriptional or post-translational mechanism. In
      addition, we observed high levels of the invariant chain (Ii/CD74) expression in
      both the cytoplasm and plasma membrane of ovarian tumor cells, possibly
      contributing to the lack of mature HLA-DR protein expression. Interestingly, we
      found that IFN-gamma could induce mature HLA-DR at the surface of normal ovarian
      cells, while this ability was reduced in tumor cells. Together, these data
      suggest that, while ovarian tumors overexpress HLA-DR alpha, perhaps as a result
      of inflammatory events in the tumor microenvironment, the tumor cells may have
      compensatory mechanisms to reduce the production of functional MHC class II
      molecules, thus reducing immunogenicity and favoring tumor growth. In addition,
      because of its ubiquitous expression in ovarian and other cancers, HLA-DR alpha
      may represent a novel biomarker for malignancy.

PMID- 15467431
TI  - PRL-3: a phosphatase for metastasis?
AB  - The PRL-3 phosphatase has joined the cancer arena very recently but is rapidly
      gaining interest both as a putative prognostic factor and as a therapeutic target
      for metastatic tumors. In this issue Guo and colleagues provide another key piece
      of information by showing that the catalytic activity of PRL-3 is required for
      experimental metastasis formation in mouse models. Here we summarize the current
      knowledge and discuss what remains to be done before PRL-3 could be considered as
      a target for diagnostics or therapeutics in the clinical setting of human cancer.

PMID- 15467432
TI  - Increased expression of dystroglycan inhibits the growth and tumorigenicity of
      human mammary epithelial cells.
AB  - Dystroglycan (DG) is an adhesion molecule formed by two subunits, alpha
      (extracellular) and beta (transmembrane) DG, which are codified by a single gene
      and form a continuous link from the extracellular matrix to the intracellular
      cytoskeleton. Reduction or loss of expression of DG has been observed in human
      cancer cell lines and primary tumors and has been suggested to promote tumor
      development and invasiveness. In this study, the human breast epithelial non
      tumorigenic MCF10F and the breast cancer MCF7 cell lines were engineered to
      stably express an exogenous DG cDNA and the effects on the phenotype of both cell
      lines were evaluated. The MCF10F transfected cells displayed an increased
      expression of both DG subunits which was associated with inhibition of the
      anchorage-dependent growth, accumulation of cells in the G0/G1 phase of the cell
      cycle and increased adhesion to a substratum. The MCF7 transfected cells were
      unable to restore alpha-DG despite an increased expression of the beta-DG
      subunit. Anchorage-dependent and independent growth and the in vivo
      tumorigenicity were reduced in these derivatives that also displayed a reduced
      adhesion to a substratum and were shown to release alpha-DG in the culture
      medium. These findings confirm and extend previous evidence that transformation
      of mammary epithelial cells is associated with loss of their ability to retain
      alpha-DG on the cell membrane. Moreover, they indicate that DG is involved in
      cell functions other than cell adhesion to the extracellular matrix, and that its
      loss of function might predispose to tumor progression by compromising regulatory
      controls over cell growth and proliferation.

PMID- 15467433
TI  - Mismatch repair gene expression and genetic instability in testicular germ cell
      tumor.
AB  - Human mismatch repair (MMR) genes encode highly conserved interacting proteins
      that correct replication errors predisposing to hereditary gastrointestinal and
      genitourinary malignancies. A subset of sporadic genitourinary tumors also
      exhibits MMR deficiency and can be identified by measuring the frequency of
      microsatellite instability (MSI) in cancer cell DNA. We investigated expression
      of the two most commonly mutated MMR genes, MSH2 and MLH1, in sporadic testicular
      germ cell tumor (GCT) in order to: (1) determine the expression pattern of MSH2
      and MLH1 proteins in normal seminiferous tubules and histologically distinct GCT
      subtypes, (2) correlate MMR gene expression with genetic instability in GCT and
      (3) develop a panel of molecular markers that can identify genetically distinct
      subsets of GCT for prognostic assessment. MSH2 and MLH1 had differential staining
      patterns in normal seminiferous tubules and malignant tissues. MSH2 was expressed
      in all stages of spermatogenesis up to but excluding mature sperm whereas MLH1
      was predominantly expressed in premeiotic germ cells. All histological GCT
      subtypes showed differential immunostaining for MSH2 and MLH1 however pure
      seminoma had statistically significant fewer low MSH2 staining tumors than other
      subtypes (p = 0.046). Twenty-five percent of GCT exhibited increased frequency of
      MSI (MSI+ tumors) with 73, 70 and 43% of MSI+ tumors exhibiting low MSH2, low
      MLH1 or low MSH2 and low MLH1 staining respectively. Fifteen percent of
      testicular GCT exhibited loss of heterozygosity (LOH) but no MSI (LOH only
      tumors). Only 28, 17 or 6% of LOH only tumors exhibited low MSH2, low MLH1 or low
      MSH2 and low MLH1 staining respectively.

PMID- 15467434
TI  - NF-kappaB activates IL-6 expression through cooperation with c-Jun and IL6-AP1
      site, but is independent of its IL6-NFkappaB regulatory site in autocrine human
      multiple myeloma cells.
AB  - IL-6 stimulates the growth and survival of a variety of tumors. In multiple
      myeloma (MM), IL-6 prevents spontaneous, drug-induced, and Fas-induced apoptosis.
      The sources of IL-6 in multiple myeloma appear to be both autocrine and paracrine
      in nature, with autocrine MM cells exhibiting a constitutively activated
      expression of the cytokine. Here we present a systematic analysis of the
      functional roles of the four major transcriptional regulatory sites present in
      the IL-6 promoter region, IL6-NFkappaB, IL6-C/EBP, IL6-CREB and IL6-AP1. Among
      these regulatory sites, IL6-AP1 is the most important cis-regulatory site, and
      plays a vital role in the constitutive expression of IL-6 in IM9 cells.
      Conversely, the IL6-CREB site, when bound by the transcription factor CREB,
      exhibits a repression of IL-6 autocrine expression, a result of possible steric
      hinderence of C/EBP-beta, due to the close proximity and site overlap between the
      IL6-C/EBP and IL6-CREB sites. Uniquely, although the presence of NF-kappaB
      protein is fundamental for constitutive expression of IL-6, a functional NF
      kappaB site on the IL-6 promoter region is not required. The mechanism of NF
      kappaB activation of IL-6 appears to occur through the cooperation with c-Jun
      protein, that constitutively occupies the IL6-AP1 site, and this indicates a
      novel transcriptional mechanism for NF-kappaB in the activation of NF-kappaB
      driven genes.

PMID- 15467435
TI  - Regulation of RARbeta1 expression in head and neck cancer cells by cell density
      dependent chromatin remodeling.
AB  - Retinoids have shown significant activities in cancer prevention and therapy.
      Many of their effects are mediated by nuclear retinoid receptors including
      retinoic acid receptors (RARs alpha, beta and gamma) and retinoid X receptors
      (RXRs alpha, beta and gamma). Human retinoic acid receptor beta (RARbeta) has
      three different isoforms: beta1, beta2 and beta4. The tumor suppressive
      characteristics of RARbeta2, its silencing by promoter hypermethylation, and its
      reexpression following demethylation have been reported. In contrast, RARbeta1,
      an embryonic isoform with restricted expression in adult tissues has been linked
      to carcinogenesis. However, factors regulating RARbeta1 expression have not yet
      been clarified. During studies on the head and neck squamous cell carcinoma
      cells, we found that the expression of RARbeta increased in cells grown to high
      density. Real-time reverse-transcriptase polymerase chain reaction revealed that
      the isoform increased in these cells was RARbeta1. Epigenetic modifications of
      this isoform were tested using combined bisulfite restriction analysis and
      chromatin immunoprecipitation assays. The UMSCC38 cell line showed significant
      RARbeta1 expression (p < 0.001), which was dependent on cell density and culture
      duration. The increased expression of RARbeta1 was not due to demethylation of
      its promoter. However, higher cell densities were associated with increased
      acetylation of histone 3 at lysine 9 in RARbeta1 but not in RARbeta2. These
      findings reveal that the expression of RARbeta1 is regulated by cell density
      through changes in histone acetylation.

PMID- 15467436
TI  - Identification of novel highly expressed genes in pancreatic ductal
      adenocarcinomas through a bioinformatics analysis of expressed sequence tags.
AB  - In most microarray experiments, a significant fraction of the differentially
      expressed mRNAs identified correspond to expressed sequence tags (ESTs) and are
      generally discarded from further analyses. We used careful bioinformatics
      analyses to characterize those ESTs that were found to be highly overexpressed in
      a series of pancreatic adenocarcinomas. cDNA was prepared from 60 non-neoplastic
      samples (normal pancreas [n = 20], normal colon [n = 10], or normal duodenal
      mucosal [n = 30]) and from 64 pancreatic cancers (resected cancers [n = 50] or
      cancer cell lines [n = 14]) and hybridized to the complete Affymetrix Human
      Genome U133 GeneChip(R) set (arrays U133A and B) for simultaneous analysis of
      45,000 fragments corresponding to 33,000 known genes and 6,000 ESTs. The
      GeneExpress(R) software system Fold Change Analysis Tool was used and 60 ESTs
      were identified that were expressed at levels at least 3-fold greater in the
      pancreatic cancers as compared to normal tissues. Searches against the human
      genomic sequence and comparative genomic analysis of human and mouse genomes was
      carried out using basic local alignment search tools (BLAST), BLASTN, and BLASTX,
      for identifying protein coding genes corresponding to the ESTs. Subsequently, in
      order to pick the most relevant candidate genes for a more detailed analysis, we
      looked for domains/motifs in the open reading frames using SMART and Pfam
      programs. We were able to definitively map 43 of the 60 ESTs to known or novel
      genes, and 15 of the ESTs could be localized in close proximity to a gene in the
      human genome although we were unable to establish that the EST was indeed derived
      from those genes. The differential expression of a subset of genes was confirmed
      at the protein level by immunohistochemical labeling of tissue microarrays
      (inhibin beta A [INHBA] and CD29) and/or at the transcript level by RT-PCR
      (INHBA, AKAP12, ELK3, FOXQ1, EIF5A2, and EFNA5). We conclude that bioinformatics
      tools can be used to characterize differentially overexpressed ESTs, and that
      some of these ESTs may represent diagnostically and therapeutically useful
      targets that might be missed using data solely from currently annotated
      databases.

PMID- 15467437
TI  - Facilitated search for specific genomic targets by p53 C-terminal basic DNA
      binding domain.
AB  - p53 is a unique DNA binding protein with two distinct DNA binding domains, the
      central domain for sequence-specific DNA binding and the C-terminal basic DNA
      binding domain (BD domain) for structure-specific DNA binding. In contrast to the
      apparent inhibitory effect of the BD domain on p53 binding to sequence-specific
      DNA in vitro, here we demonstrate that the BD domain enhances p53 binding to the
      endogenous p21(Waf1) promoter and mediates rapid transactivation of p21.(Waf1)
      This paradox is resolved by the observation that the BD domain is required for
      rapid binding to non-sequence-specific genomic DNA (NS-DNA) as evident from
      global chromatin immunoprecipitation analysis of p53 DNA binding in vivo. This
      finding provides the first in vivo evidence from a eukaryotic system to support
      binding to NS-DNA as an intermediate step in searching for specific sites as
      proposed by von Hippel and Berg. Furthermore, we speculate that binding to
      structure-specific DNA by the BD domain is a mechanism for p53 rapid binding to
      genomic DNA from its free state to facilitate the search for its target sites in
      the genome undergoing genotoxic stress.

PMID- 15467438
TI  - Molecular profiling of embryonal carcinoma cells following retinoic acid or
      histone deacetylase inhibitor treatment.
AB  - Regulation of tissue homeostasis is crucial to disease prevention; cell division,
      cell cycle arrest, differentiation and apoptosis have to be tightly controlled in
      order to maintain this homeostasis. Retinoic acid (RA) and the histone
      deacetylase inhibitors (HDACIs) have profound effects on these processes and thus
      may be critical regulators of homeostasis. Consequently, RA and/or histone
      deacetylase inhibitors are currently being tested in clinical trials for a
      variety of cancers. Unfortunately, little is known of the overall affect of these
      compounds on cellular gene expression. Therefore, we decided to compare the
      effects of all-trans retinoic acid (ATRA) and a particular HDACI-Trichostatin A
      (TSA)-on an embryonal carcinoma (EC) cell line (F9) using gene chip analysis. We
      have focused particular attention on those genes that may be differentially
      affected by these compounds. Within the parameters established for this study,
      only 116 of the 12,488 genes examined were similarly regulated by ATRA and TSA:
      75 positively and 41 negatively. An additional 70 genes were affected by only one
      of the compounds and 19 genes were actually inversely regulated. The gene set
      inversely regulated by ATRA and TSA includes several important patterning genes
      as well as the crucial tumor suppressor/promoter, transforming growth factor beta
      1 (TGFbeta1). Promoter analysis suggests a motif that may regulate one set of
      these genes. This study provides the first comprehensive comparison of global
      gene expression on EC cells as affected by ATRA and a HDAC inhibitor (TSA);
      reveals new targets for ATRA and HDAC inhibitors; identifies a new regulatory
      motif; demonstrates that ATRA and HDAC inhibitors do not always act
      synergistically on gene expression; and examines particular questions regarding
      their concurrent clinical application.

PMID- 15467439
TI  - CD2-SLFA3/T11TS interaction facilitates immune activation and glioma regression
      by apoptosis.
AB  - OBJECTIVE: Exogenous application of T11TS/SLFA3 in glioma model had shown the
      regression of tumor load through immunopotentiation. The mechanistic module of
      this interaction on immunological synapse formation and resulting effect in
      glioma regression is searched for delineating immunotherapeutic efficacy of
      T11TS. METHODS: After purification of T11TS/SLFA3 from sheep erythrocytes the
      glycoprotein was characterized by SDS-PAGE analysis and glycoprotein staining.
      The modulatory effect of T11TS application on glioma animals were studied by CD2
      and MHC class II expression on peripheral lymphocytes, PMN, macrophages and
      intracranial microglia by flowcytometric analysis. Finally apoptotic killing of
      brain cells were studied through annevin-V expression and measuring fragmented
      cytoplasmic DNA by ELISA. RESULTS: Compared to healthy normal counter-parts the
      CD2 receptor downregulation by ENU treatment in lymphocytes and PMN were
      upregulated with three consecutive doses of T11TS. Splenic antigen presenting
      macrophages and intracranial mocroglia had shown CD2 and MHC class II modulation
      simultaneously in their different subtypes. These receptor studies revealed
      significant boosting of the immune competent cells most effectively in second
      dose of T11TS whereas the third dose had some regulatory effect. Sharp increase
      of apoptosis in brain cells was found by phosphatidylserine externalization and
      presence of fragmented DNA in cytoplasm with application of T11TS in consecutive
      doses as a result of immune potentiation. CONCLUSION: Receptor studies revealed
      modulation of CD2 and MHC class II, two important constituents of immunological
      synapse successfully help to form the TCR-p-MHC complex and provide required co
      stimulation for activation. Potentiated immune effector machinery was then
      directed to abrogate glioma by apoptosis signifying T11TS as an immunotherapeutic
      probe.

PMID- 15467440
TI  - The farnesyltransferase inhibitor Lonafarnib induces growth arrest or apoptosis
      of human lung cancer cells without downregulation of Akt.
AB  - Farnesyltransferase inhibitors (FTIs) have been demonstrated to induce growth
      arrest or apoptosis independent of Ras mutation. Alternatively, Akt has been
      proposed as a potential target for the FTI's actions. This study investigated
      whether Lonafarnib was effective in inhibiting the growth of human nonsmall cell
      lung cancer (NSCLC) cells and elucidated the role of Akt in mediating such growth
      inhibitory effects. Lonafarnib, at clinical achievable concentration ranges, was
      effective in inhibiting the growth of 10 NSCLC cell lines, particularly after a
      prolonged treatment, regardless of Ras mutational status. Lonafarnib arrested
      cells growth at G(1) or G(2)/M phase in the majority tested cell lines. However
      it induced apoptosis when cells were cultured in a low serum (0.1%) medium. The
      majority of NSCLC cell lines expressed undetectable level of phosphorylated Akt
      (p-Akt). Lonafarnib at up to 10 muM did not decrease either total Akt level or p
      Akt level in any of the tested cell lines, even after a 48 h treatment.
      Unexpectedly, Lonafarnib even increased p-Akt level in one cell line, although it
      was as sensitive as others to Lonafarnib treatment and underwent G(2)/M arrest.
      Bovine serum albumin completely rescued cells from Lonafarnib-induced apoptosis
      in low serum medium, indicating that proteins rather than cytokines or growth
      factors in serum masks Lonafarnib's pro-apoptotic effect. Therefore, we conclude
      that Lonafarnib is effective in inhibiting the growth of NSCLC cells either via
      growth arrest or induction of apoptosis without downregulation of Akt.

PMID- 15467441
TI  - Cell cycle effects and induction of premitotic apoptosis by irofulven in
      synchronized cancer cells.
AB  - Unlike postmitotic cell death, direct premitotic apoptosis diminishes the risk of
      clonal selection and allows for the elimination of slowly growing cancer cells.
      This study characterized the ability to induce premitotic apoptosis by irofulven
      (hydroxymethylacylfulvene), a novel alkylating drug which targets cellular DNA
      and proteins. Irofulven effects were examined in HeLa-derived BH2 cancer cells
      with conditional overexpression of antiapoptotic Bcl-2. Cells were synchronized
      in either early S or in G(1). Following 12 h exposure to irofulven, cells that
      were originally in early S accumulated in late S or remained in early S phase (at
      0.5 and 2.5 muM drug, respectively). Drug treatment of cells in the G(1) cohort
      prevented their entry into the S phase. Significant apoptosis was detected based
      on the appearance of sub-G(1) particles and cells with DNA strand breaks in both
      G(1) and S cohorts. Apoptotic cells were mostly recruited from the G(1)/S border
      ("G(1)" cohort) and from the S phase ("early S" cohort). All the cell cycle and
      apoptotic effects were only marginally affected by Bcl-2 overexpression. Similar
      results were obtained with irofulven-treated synchronized cultures of leukemic
      CEM cells. Collectively, these observations indicate that irofulven-treated cells
      become committed to death early. Neither active DNA replication nor traverse
      through mitosis are necessary for irofulven-induced cell death. The ability to
      promote direct premitotic apoptosis is likely to play a role in the consistently
      potent apoptotic effects of irofulven and its ability to cause tumor regression
      in vivo.

PMID- 15467442
TI  - Ribozyme targeting HPV16 E6E7 transcripts in cervical cancer cells suppresses
      cell growth and sensitizes cells to chemotherapy and radiotherapy.
AB  - Human Papillomavirus (HPV) is related to more than 90% of cervical cancer. The
      virus is shown to be essential for the induction and maintenance of the malignant
      phenotype in cervical cancer. In this report, we designed a hammerhead ribozyme
      Rz170 to specifically target the HPV16 E6E7 transcripts, and our results
      demonstrated that Rz170 can cleave HPV16 E6E7 transcripts effectively and with
      high specificity. When transfected into a HPV16 positive cervical cancer cell,
      CaSKi, the ribozyme reduced the expression of HPV16 E6 and E7 mRNA, and inhibited
      cell growth both in vitro and in vivo. The percentage of apoptosis cells was also
      increased. We found that Rz170 reduced the expression of the viral E6 and E7
      proteins, and cellular c-myc, bcl-2 proteins, but increased the expression of p53
      and Rb proteins. It is likely that the ribozyme inhibited cervical cancer cell
      growth by reducing the expression of the HPV16 E6 and E7gene, which may alter the
      expression of p53, Rb, c-myc and bcl-2, and led to apoptosis in cancer cells. We
      also found that CaSKi cells transfected with Rz170 showed increased sensitivity
      to cisplatin and radiation. Our study demonstrated the potential of Rz170 for
      treating cervical cancer, and the possibility of using a combined therapeutic
      strategy involving ribozyme, chemotherapy or radiotherapy.

PMID- 15467443
TI  - Treatment of chronic myeloid leukemia cells with imatinib (STI571) impairs p53
      accumulation in response to DNA damage.
AB  - Chronic myelogenous leukaemia (CML) is induced by the Bcr-Abl fusion protein.
      Inhibition of Bcr-Abl by STI571 is widely used to treat CML patients. Unlike in
      most cancer types, the frequency of p53 mutations in CML is low. Here, we
      investigated the effect of STI571 treatment of CML cells on p53 regulation.
      Exposure of CML cells, including established cell lines and freshly isolated
      cells from patients, to STI571 reduced p53 protein levels, and severely impaired
      its accumulation in response to DNA damage. This may be explained by the status
      of p53 serine 20 phosphorylation. In non-stressed CML cells, serine 20 of p53 is
      constitutively phosphorylated by Chk1, and is inhibited by STI571. In response to
      DNA damage, however, this phosphorylation is mediated by Chk1 and Chk2, and is
      only partially inhibited by STI571. CML cells expressing wild-type p53 are more
      resistant to treatment with STI571, but moderately more sensitive to DNA damage,
      than CML cells lacking p53. An enhanced induction of apoptosis by STI571 and DNA
      damage is observed in CML cells bearing wild-type p53, but not in cells lacking
      functional p53. This implies that the status of p53 may affect the response of
      CML cells to this combined treatment.

PMID- 15467444
TI  - Regulation in S phase by E2F.
AB  - The DNA synthetic S phase of the unperturbed cell cycle is a closed system, as
      compared to regulation of G(1) by external growth factors. The E2F family
      provides internal control in S phase by transcribing genes required for
      deoxynucleotide triphosphate (dNTP) and DNA synthesis. Furthermore, over
      expression of E2F-1 activates programmed cell death (apoptosis), a safeguarding
      signal of aberrant growth of cells that have become carcinogenic. Mechanisms for
      control of E2F-1 are thus essential. The hypothesis is proposed that
      deoxythymidine triphosphate (dTTP) allosterically feedback controls E2F-1 to
      regulate both DNA synthesis and apoptosis. This may act either upon production of
      E2F-1 or its degradation.

PMID- 15467445
TI  - Rescue of the TTF2 knockdown phenotype with an siRNA-resistant replacement
      vector.
AB  - TTF2 is an RNA polymerase II termination factor that is responsible for mitotic
      repression of transcription elongation. Normally, all RNA polymerase II molecules
      are eliminated from condensed mitotic chromosomes, but siRNA-mediated knockdown
      of TTF2 causes a phenotype in which polymerases are retained on mitotic
      chromosomes. To prove that this phenotype is due to reduced TTF2 activity we have
      created an siRNA-resistant TTF2 replacement vector that expresses an mRNA
      encoding GFP-tagged TTF2 that contains silent mutations in the region that is
      targeted by the siRNA. Transient transfection experiments demonstrate that
      endogenous TTF2 and GFP-tagged wild-type TTF2 are both sensitive to the siRNA,
      but GFP-tagged TTF2 encoded by the cDNA containing mismatches is abundantly
      expressed in the presence of TTF2-siRNA. Importantly, the mitotic phenotype seen
      with TTF2-siRNA is rescued by expression of the siRNA-resistant GFP-tagged TTF2
      proving that reduced TTF2 is responsible for the retention of RNA polymerase II
      on mitotic chromosomes.

PMID- 15467446
TI  - Telomeres, telomerase and cancer: an endless search to target the ends.
AB  - Maintenance of functional telomeres, the highly complex nucleo-protein
      structures, at the end of linear eukaryotic chromosomes appears to be essential
      for growth and survival of the cells. The compelling correlation between
      telomerase reactivation and cellular immortalization led to the idea that
      inhibition of telomerase may provide a way for effective hindrance of cancer cell
      growth by interfering with telomere maintenance. In addition to targeting the
      components of telomerase enzyme directly to prevent telomere synthesis, several
      approaches including disruption of telomeres, interference with telomerase
      component assembly, translocation of the catalytic component of telomerase have
      also been under extensive investigation due to the advances in understanding the
      biology of telomeres and telomerase in recent years. This review will focus on
      the so far identified approaches to prevent cancer cell growth by targeting
      telomerase and telomeres with a brief introduction about structure and function
      of telomeres and telomerase.

PMID- 15467447
TI  - The life cycle of C-myc: from synthesis to degradation.
AB  - The c-Myc transcription factor is a potent regulator of cellular proliferation
      and cell fate decision. Precise regulation of c-Myc protein levels is essential
      to maintain normal cell function. In order to maintain proper levels of c-Myc,
      its protein stability is tightly controlled. c-Myc is degraded through the
      ubiquitin-proteasome pathway. This perspective discusses a sophisticated and
      complex signaling pathway that controls the life cycle of c-Myc from protein
      synthesis to ubiquitin-mediated degradation. The pathway involves Ras-activated
      kinases, the Pin1 prolyl isomerase, the PP2A phosphatase and a series of c-Myc
      phosphorylation and dephosphorylation events that control its stability.

PMID- 15467448
TI  - Rusticyanin, a bacterial electron transfer protein, causes G1 arrest in J774 and
      apoptosis in human cancer cells.
AB  - During acid mine drainage, Acidithiobacillus ferrooxidans, a nonpathogenic,
      acidophilic, lithotrophic bacterium, utilizes rusticyanin to transfer electrons
      for the oxidation of Fe(2+) to Fe(3+) for deriving its energy. No other function
      of rusticyanin is known. We demonstrate that purified rusticyanin enters
      mammalian cells inducing either inhibition of cell cycle progression or caspase-8
      mediated apoptosis. Treatment of human melanoma cells with rusticyanin allowed
      significant generation of reactive oxygen species and active caspase-8, leading
      to cell death. The ability of rusticyanin to modulate mammalian cell death might
      be relevant to a role of this cupredoxin in protecting At. ferrooxidans from
      eukaryotic predators in the environment.

PMID- 15467449
TI  - The cyclin-dependent kinase inhibitor p21(CIP1/WAF1) blocks paclitaxel-induced
      G2M arrest and attenuates mitochondrial injury and apoptosis in p53-null human
      leukemia cells.
AB  - The functional significance of the cyclin-dependent kinase inhibitor (CDKI)
      p21(Cip1/WAF1) in paclitaxel-mediated lethality was examined in p53-null human
      leukemia cells (U937 and Jurkat). In these cells, paclitaxel exposure failed to
      induce p21(Cip1/Waf1) expression. Nevertheless, stable expression of U937 cells
      with a p21(Cip1/WAF1) antisense construct blocked paclitaxel-induced G(2)M arrest
      and increased mitochondrial injury, caspase activation, apoptosis, and loss of
      clonogenic potential. Consistent with these results, enforced expression of
      p21(Cip1/WAF1) in Jurkat cells increased the percentage of cells arrested in G2M
      and attenuated paclitaxel-mediated mitochondrial injury and apoptosis.
      Unexpectedly, enforced expression of p21(Cip1/WAF1) diminished paclitaxel
      mediated inactivation of ERK, and reduced paclitaxel-induced activation of JNK as
      well as Bcl-2 phosphorylation. Together, these findings suggest that
      p21(Cip1/WAF1) partially protects p53-null human leukemia cells from paclitaxel
      mediated lethality, and raise the possibility that p21(Cip1/WAF1)-associated
      perturbations in signal transduction pathways as well as Bcl-2 phosphorylation
      status may play a role in this phenomenon.

PMID- 15467450
TI  - JNK is associated with Bcl-2 and PP1 in mitochondria: paclitaxel induces its
      activation and its association with the phosphorylated form of Bcl-2.
AB  - It has been shown that the activation of JNK after paclitaxel-induced microtubule
      damage is parallel to Bcl-2 phosphorylation, cell cycle arrest in mitosis and
      apoptosis. Using subcellular fractionation and immunocytochemistry, we found here
      that a pool of activated JNK is located in mitochondria of HeLa cells treated
      with paclitaxel. Furthermore, whereas the JNK protein is present in a tripartite
      complex with the anti-apoptotic Bcl-2 protein and the PP1 phosphatase in
      mitochondria isolated from control cells, the activated form of JNK was
      associated with the phosphorylated form of Bcl-2, but devoid of PP1, in
      mitochondria isolated from paclitaxel-treated cells. Moreover, using an original
      cell-free system, we evidenced a direct involvement of JNK as the kinase
      responsible for the phosphorylation of mitochondrial Bcl-2 in mitotic arrested
      cells. Indeed, cytosols prepared from mitotic arrested cells led to a dose
      dependent phosphorylation of mitochondrial Bcl-2. Bcl-2 phosphorylation was
      inhibited by CEP 11004, a JNK pathway inhibitor and by immunodepletion of JNK.
      Taken together, these data show that JNK activation provides a molecular linkage
      from microtubule damages to the mitochondrial apoptotic machinery and also point
      to a pivotal role for the JNK/Bcl-2/PP1 complex in the control of apoptosis
      following paclitaxel treatment.

PMID- 15467451
TI  - A novel role for mixed lineage kinase 3 (MLK3) in B-Raf activation and cell
      proliferation.
AB  - The extracellular signal-regulated kinase (ERK) group of MAPKs is essential for
      cell proliferation, including that stimulated by mitogens, oncogenic ras and raf.
      The Raf kinases (especially B-Raf) are ERK-specific, mitogen-activated MAP3Ks.
      Mixed lineage kinase-3 (MLK3) is a MAP3K previously thought to be a selective
      regulator of the JNK group of MAPKs. Surprisingly, we found that silencing of
      mlk3 by RNAi suppresses mitogen and cytokine activation not only of JNK but of
      ERK and p38 as well. Silencing mlk3 also blocks mitogen-stimulated
      phosphorylation of B-Raf at Thr598 and Ser601-a step required for B-Raf
      activation. Finally, silencing mlk3 prevents serum-stimulated cell proliferation
      and the proliferation of tumor cells bearing either oncogenic Ki-Ras or loss of
      function neurofibromatosis-1 (NF1) or NF2 mutations. The proliferation of tumor
      cells with activating mutations in B-raf or raf-1 are unaffected by silencing
      mlk3. These results define a new role for MLK3 in B-Raf activation, ERK signaling
      and cell proliferation. Accordingly, targeting MLK3 could be beneficial to the
      treatment of tumors with activated receptor tyrosine kinase or ras mutations, and
      to the treatment of NF1 or NF2 tumors.

PMID- 15467452
TI  - A genetic oscillator and the regulation of cell cycle progression in Caulobacter
      crescentus.
AB  - Analyses of cell polarity, division, and differentiation in prokaryotes have
      identified several regulatory proteins that exhibit dramatic changes in
      expression and spatial localization over the course of a cell cycle. The dynamic
      behavior of these proteins is often intrinsically linked to their function as
      polarity determinants.(1-3) In the alpha-proteobacterium, Caulobacter crescentus,
      the CtrA global transcriptional regulator exhibits a spatially and temporally
      dynamic expression pattern across the cell cycle. CtrA plays key roles in
      asymmetric cell division and in the timing of chromosome replication.(3,4) An
      additional global regulator, GcrA, has recently been discovered that both
      regulates and is regulated by CtrA.(5) Together, these regulatory proteins create
      a genetic circuit in which the cellular concentrations of CtrA and GcrA oscillate
      spatially and temporally to control daughter cell differentiation and cell cycle
      progression.

PMID- 15467453
TI  - Hypoxia causes aggregation of serine palmitoyltransferase followed by non
      apoptotic death of human lymphocytes.
AB  - In the central nervous system chronic hypoxia has been suggested to cause
      neurodegenerations and protein aggregation, as in Alzheimer's disease. Here we
      have shown protein aggregation during acute hypoxia in human primary cells.
      Clinically relevant acute hypoxia (pO(2) = 25 mmHg) was produced by incubation of
      venous blood in vitro, where 18-hour incubation resulted in raise of pCO(2) to 90
      mmHg, accumulation of lactate and acidosis (pH 7.06). In hypoxic samples the
      number of necrotic, but not apoptotic, white blood cells increased to 9.6%.
      Viable cells displayed hypoxia-related changes such as a drop of mitochondrial
      membrane potential and changes in the plasma membrane. These changes coincided
      with the 2.6-fold increase in immunoreactivity of serine palmitoyltransferase
      subunit 1 (SPT1), which is the enzyme involved in HSN1-type neurodegeneration.
      SPT1 immunoreactivity was presented as large cytosolic aggregates, which appeared
      in viable hypoxic cells and remained in dead cells. SPT-positive aggregates were
      also found in cell nuclei. This data suggests that SPT1 aggregation preceded cell
      death in hypoxia and represents the first evidence of acute protein aggregation
      during hypoxia.

PMID- 15467454
TI  - Chromosome 17p deletion in human medulloblastoma: a missing checkpoint in the
      Hedgehog pathway.
AB  - Although deregulation of Hedgehog signalling is considered to play a crucial
      oncogenic role and commonly occurrs in medulloblastoma, genetic lesions in
      components of this pathway are observed in a minority of cases. The recent
      identification of a novel putative tumor suppressor (REN(KCTD11)) on chromosome
      17p13.2, a region most frequently lost in human medulloblastoma, highlights the
      role of allelic deletion of the gene in this brain malignancy, leading to the
      loss of growth inhibitory activity via suppression of Gli-dependent activation of
      Hedgehog target genes. The presence on 17p13 of another tumor suppressor gene
      (p53) whose inactivation cooperates with Hedgehog pathway for medulloblastoma
      formation, suggests that 17p deletion unveils haploinsufficiency conditions
      leading to abrogation of either direct and indirect checkpoints of Hedgehog
      signalling in cancer.

PMID- 15467455
TI  - RACK1 and stratifin target DeltaNp63alpha for a proteasome degradation in head
      and neck squamous cell carcinoma cells upon DNA damage.
AB  - p53 family members with a transactivation (TA) domain induce cell cycle arrest
      and promote apoptosis. However, DeltaNp63 isotypes lacking the TA-domain promote
      cell proliferation and tumorigenesis in vitro and in vgammavo. Although p53,
      TAp63 or TAp73 are stabilized upon DNA damage, we found that the genotoxic stress
      agents induced a dramatic decrease and phosphorylation of DeltaNp63alpha in
      squamous cell carcinoma cells. Further work revealed that RACK1 physically
      associated with the p63alpha C-terminal domain through its WD40 domain. However,
      stratifin binds with phosphorylated DeltaNp63alpha in response to cisplatin. Upon
      DNA damage induced by cisplatin, stratifin mediated a nuclear export of
      DeltaNp63alpha into cytoplasm and then RACK1 targeted latter into a proteasome
      degradation pathway possibly serving as an E3 ubiquitin ligase. Moreover, siRNA
      knockdown of both stratifin and RACK1 inhibited a nuclear export and protein
      degradation of DeltaNp63alpha, respectively. Our data suggest that modification
      and down regulation of DeltaNp63alpha is one of the major determinants of the
      cellular response to DNA damage in human head and neck cancers.

PMID- 15467456
TI  - Werner syndrome protein and the MRE11 complex are involved in a common pathway of
      replication fork recovery.
AB  - Werner syndrome (WS) is an autosomal recessive disease that predisposes
      individuals to a wide range of cancers. The gene mutated in WS, WRN, encodes a
      member of the RecQ family of DNA helicases. The precise DNA metabolic processes
      in which WRN participates remain to be elucidated. However, it has been proposed
      that WRN might play an important role in the maintenance of genetic stability
      during DNA replication, possibly cooperating with other proteins. Here, we show
      that, following DNA replication arrest, WRN associates and colocalizes with the
      MRE11 complex at PCNA sites. We also provide evidence that both WRN/MRE11 complex
      association and proper WRN relocalization after HU treatment require a functional
      MRE11 complex. We demonstrate that mutations altering the functionality of WRN or
      that of the MRE11 complex result in chromosomal breakage during DNA replication
      and enhanced cell death following replication arrest. Finally, we show that the
      DNA breakage in replicating cells and apoptosis observed in WS are not enhanced
      by concomitant knock down of MRE11 by RNAi, indicating that WRN and MRE11 complex
      act in a common pathway. These results suggest a functional relationship between
      WRN and the MRE11 complex in response to replication fork arrest, disclosing a
      common action of WRN and the MRE11 complex in the pathway(s) preserving genome
      stability during DNA replication.

PMID- 15467458
TI  - Dysfunctional telomeres at senescence signal cell cycle arrest via Chk2.
AB  - Loss of telomere integrity can have two outcomes with opposite predicted effects
      on tumorigenesis. On the one hand, shortened telomeres in normal cells may
      trigger cell cycle arrest, leading to tumor suppression. On the other hand, in a
      tumor cell in which neither the p53 nor pRb pathway is intact, shortened
      telomeres could initiate chromosome instability and promote tumorigenesis A major
      issue in telomere research is to understand how shortened dysfunctional telomeres
      can regulate the onset of cellular senescence. Recent studies have revealed that
      critically shortened or acutely uncapped telomeres share molecular features with
      damaged DNA. We have recently linked the phosphorylation and activation of one
      major DNA damage effector checkpoint kinase, Chk2, to telomere erosion in
      signalling cell cycle arrest in normal fibroblasts. Here, we discuss several
      hypotheses to explain the molecular events occurring at shortened telomeres that
      ultimately lead to cell cycle arrest or increased genomic instability.

PMID- 15467457
TI  - A dynamic equilibrium between CDKs and PP2A modulates phosphorylation of pRB,
      p107 and p130.
AB  - It is thought that G(1) cyclin/CDK mediated phosphorylation of pocket proteins
      from mid G(1) to mitosis is reversed via dephosphorylation in mitosis. We
      examined the mechanisms involved in the unexpectedly rapid dephosphorylation of
      the pocket proteins induced via inhibition of cellular protein synthesis by
      cycloheximide (CHX) as well as direct inhibition of CDKs by flavopiridol. CHX and
      flavopiridol-induced dephosphorylation of pocket proteins is attributable to
      inactivation of D-type cyclin/CDKs and G(1)/S CDKs, respectively, which unmasks a
      phosphatase activity that targets the three pocket proteins apparently throughout
      the cell cycle. Treatment of cells with phosphatase inhibitors at concentrations
      selective for PP2A inhibition prevents CHX and flavopiridol-mediated
      dephosphorylation of pocket proteins in vivo. Also, ectopic expression of SV40
      small t antigen, which inhibits PP2A via disruption of trimeric PP2A holoenzymes,
      delays CHX-induced pocket protein dephosphorylation. Moreover, dephosphorylation
      of p130 and p107 in cell extracts is inhibited by concentrations of okadaic acid
      known to inhibit PP2A, but not PP1. Finally, the PP2A catalytic subunit (PP2A/C)
      specifically interacts with both p130 and p107 in quiescent cells as well as
      cells progressing throughout the cell cycle. Together, these results demonstrate
      that the overall phosphorylation state of pocket proteins is determined, at least
      in part, by a dynamic equilibrium between CDKs and PP2A, or a closely related
      PP2A-like enzyme. These findings have important implications, as cell cycle or
      checkpoint-dependent inhibition of CDK activities counteracted by an active PP2A
      should have imminent effects on the phosphorylation state and activities of
      pocket proteins.

PMID- 15467459
TI  - Multi-kinase phosphorylation of the APC/C activator Cdh1 revealed by mass
      spectrometry.
AB  - Cdh1 contributes to proper exit from mitosis and maintenance of G(1) phase in
      eukaryotic cells by activating a large ubiquitin ligase called the anaphase
      promoting complex, or cyclosome (APC/C). At the end of G(1), APC/C(Cdh1) is
      inhibited by cyclin-dependent kinase (CDK) phosphorylation of Cdh1. The specific
      Cdh1 phosphorylation sites used to regulate APC/C(Cdh1) activity have not been
      directly identified. Here, we used a mass spectrometric approach to identify the
      in vivo phosphorylation sites on yeast Cdh1. Surprisingly, in addition to several
      expected CDK phosphorylation sites, we discovered numerous nonCDK phosphorylation
      sites. In total, at least 19 serine and threonine residues on Cdh1 are
      phosphorylated in vivo. Seventeen of these sites are located in the N-terminal
      half of Cdh1, outside the highly conserved WD40 repeats. The pattern of
      phosphorylation was the same when Cdh1 was purified from yeast cultures arrested
      in S, early M and late M. Mutation of CDK consensus sequences eliminated
      detectable phosphorylation at many of the nonCDK sites. In contrast, mutation of
      nonCDK sites had no significant effect on CDK phosphorylation. We conclude that
      phosphorylation of CDK sites promotes the subsequent recognition of Cdh1 by at
      least one additional kinase. The function of nonCDK phosphorylation may differ
      from CDK phosphorylation because mutation of nonCDK sites did not result in
      constitutive activation of APC and consequent cell cycle arrest. These results
      suggest that phosphoregulation of APC/C(Cdh1) activity is much more complex than
      previously thought.

PMID- 15467460
TI  - Ras/Raf/ERK signalling and NF1.
AB  - Ras signalling is important in the development of Schwann-cell-derived tumors in
      Neurofibromatosis Type 1 (NF1) patients. Schwann cells are a regenerative cell
      type, with no known stem-cell population. To produce new cells in the adult, for
      example following nerve damage, myelinating Schwann cells de-differentiate,
      proliferate and then re-differentiate during the repair process. We have found
      that Ras/Raf/ERK signalling can drive the de-differentiation of myelinated
      Schwann cells. In this review, we discuss how our results may contribute to the
      understanding of tumor formation in NF1 patients.

PMID- 15467461
TI  - Playing polo in G1: a novel function of polo-like kinase-2 in centriole
      duplication.
AB  - Centrosomes contain a pair of centrioles that duplicate once during the cell
      cycle to give rise to two mitotic spindle poles, each containing one old and one
      new centriole. Centrosome duplication initiates at the G(1)/S transition in
      mammalian cells, and is completed during S and G(2) phase. The localization of a
      number of protein kinases to the centrosome has revealed the importance of
      protein phosphorylation in controlling the centrosome duplication cycle. Recent
      studies have shown that polo-like kinase-2 is required for centriole duplication
      in mammalian cells. In this article I discuss the implication of these findings
      to our current understanding of centrosome duplication.

PMID- 15467462
TI  - The relevance of NF-kappaB for CD95 signaling in tumor cells.
AB  - Most members of the death receptor family including CD95 (APO-1/Fas) have been
      shown to induce both apoptosis as well as non-apoptotic pathways depending on the
      tissue and the circumstances. One of the non-apoptotic pathways emanating from
      CD95, activation of NF-kappaB, has recently been demonstrated to regulate
      invasiveness of apoptosis resistant tumor cells. In contrast, activation of NF
      kappaB in apoptosing cells is believed to be suppressed due to cleavage of
      various NF-kappaB pathway components by active caspases that execute apoptosis.
      We now present data demonstrating that in certain highly CD95 apoptosis sensitive
      cells NF-kappaB is robustly activated. In fact overexpression of apoptosis
      inhibitors such as Bcl-2 or c-FLIPL in these cells results in decreased
      activation of NF-kappaB through CD95. We propose a model in which NF-kappaB is
      generally activated in certain cells but may have different functions depending
      on whether cells are programmed to die or to survive.

PMID- 15467463
TI  - Mcl-1 regulation and its role in multiple myeloma.
AB  - Among the Bcl-2 family, myeloid cell leukemia-1 (Mcl-1) distinguishes itself from
      the other pro-survival proteins by its ability to oppose to a wide variety of pro
      apoptotic stimuli, short half-life, and presence of polypeptide sequences
      enriched in proline (P), glutamic acid (E), serine (S) and threonine (T) domains
      (PEST). Moreover, Mcl-1 undergoes a complex transcriptional, post
      transcriptional, and post-translational regulation process. This regulation
      modifies not only Mcl-1 expression, but also its function. Various extra-cellular
      stimuli, including cytokines, growth factors, 12-O-tetradecanoyl-phorbol 13
      acetate (TPA) and IFN, activate pathways which regulate Mcl-1 expression.
      Furthermore, Mcl-1 can be alternatively spliced into a long (Mcl-1) or a short
      (Mcl-1S) form. Mcl-1 opposes pro-apoptotic proteins and can be either cleaved or
      phosphorylated at a post-translational level. Mcl-1-spliced products, Mcl-1
      cleaved products, or phosphorylated Mcl-1 have either a pro or an anti-apoptotic
      function, highlighting the complexity and pivotal role of Mcl-1 regulation. Here
      we discuss the regulation and function of Mcl-1 in the pathophysiology of
      multiple myeloma.

PMID- 15467464
TI  - Evolutionary conservation of a novel splice variant of the Cds1/CHK2 checkpoint
      kinase restricted to its regulatory domain.
AB  - The Cds1/CHK2 kinase plays a key role in the activation of the G(2) checkpoint
      after DNA damage. Here we report the existence in fission yeast of a short
      variant (Sv) of Cds1 that is produced through an alternative splicing mechanism
      leading to a frame shift and premature termination. This SvCds1 protein consists
      solely of the regulatory region and lacks the catalytic domain. Expression of
      SvCds1 increases sensitivity to ionizing radiation and, to a lesser extent, to
      hydroxyurea, but not to UV radiation. We also report that in the human orthologue
      of Cds1, CHK2, differential splicing of a cryptic exon leads to a frame shift and
      premature termination producing a short variant (SvCHK2). Thus, we have
      discovered the existence of an evolutionary conserved mechanism ensuring the
      production of a catalytically inactive variant Cds1/CHK2 that is restricted to
      SQTQ and FHA domains and that can act as a dominant negative. The role that this
      short variant of Cds1/CHK2 might play in the response to DNA damage and the
      physiopathological consequences are discussed.

PMID- 15467465
TI  - Metastasizing and non-metastasizing tumors likely evolve from DNA phenotypes via
      independent pathways.
AB  - We have recently discovered, using statistical models of Fourier transform
      infrared spectra, two distinct cancer DNA phenotypes in histologically normal
      tissues surrounding non-metastasizing primary tumors and tumors with evidence of
      distant metastases. Structural comparisons of the DNA from these tumor types
      imply that each evolves via a separate pathway from DNA phenotypes originating in
      progenitor cells. These findings challenge the widely-held concept of metastasis.

PMID- 15467466
TI  - A zebrafish model of germ cell aneuploidy.
AB  - The high frequency of chromosomal nondisjunction in human germ cells impacts
      society in many ways. Yet, the etiology of chromosome disorders remains unclear.
      Using a zebrafish strain with a hypomorphic mutation in the kinase Mps1, a
      genetic association between reduced germ cell mitotic checkpoint activity and
      aneuploid progeny was recently established. This work highlights the exquisite
      sensitivity of vertebrate germ cells to disruptions in Mps1 function and mitotic
      checkpoint activity. In addition, it introduces the zebrafish as a promising tool
      with which to further investigate the origins of aneuploidy.

PMID- 15467467
TI  - Magnifying stem cell lineages: the stop-EGFP mouse.
AB  - Cell fate mapping techniques which can label clonal cell lineages are of
      importance because they allow one to investigate the distribution and types of
      daughter cells arising from single precursor cells. Thus, the potential of
      precursor cells to generate various types of descendent cells can be studied at
      the single-cell level. The stop-EGFP transgenic mouse carries a premature stop
      codon-containing enhanced green fluorescent protein (EGFP) gene as a target gene
      for mutations. A cell having undergone a mutation at the premature stop codon and
      its descendant cell lineage will express EGFP, thus a clonal cell lineage can be
      traced in vivo using a fluorescent microscope. Using the stop-EGFP mouse, stem
      cell clonal lineages in the mouse dorsal epidermis can be investigated in vivo
      and repeated analyses of the same cell lineages can be performed over time. In
      vivo imaging studies possible with the stop-EGFP mouse provide new insights into
      the structure of epidermal proliferative units (EPUs). The stop-EGFP system
      provides a novel tool for investigating clonal cell lineages in developmental
      studies as well as in stem cell biology.

PMID- 15467468
TI  - Oncogenic mutations of PIK3CA in human cancers.
AB  - Phosphatidylinositol 3-kinases (PI3Ks) are important regulators of signaling
      pathways. To determine whether PI3Ks are genetically altered in human cancers, we
      recently analyzed the sequences of the PI3K gene family and discovered that one
      member, the PIK3CA gene encoding the p110alpha catalytic subunit, was frequently
      mutated in cancers of the colon, breast, brain and lung. The majority of
      mutations clustered near two positions within the PI3K helical or catalytic
      domains and at least one hotspot mutation appeared to increase kinase activity.
      PIK3CA represents one of the most highly mutated oncogenes identified in human
      cancers and may be a useful diagnostic and therapeutic target.

PMID- 15467470
TI  - Potential roles for centromere pairing in meiotic chromosome segregation.
AB  - One of the key differences between mitosis and meiosis is the necessity for
      exchange between homologous chromosomes. Crossing-over between homologous
      chromosomes is essential for proper meiotic chromosome segregation in most
      organisms, serving the purpose of linking chromosomes to their homologous
      partners until they segregate from one another at anaphase I. In several
      organisms it has been shown that occasional pairs of chromosomes that have failed
      to experience exchange segregate with reduced fidelity compared to exchange
      chromosomes, but do not segregate randomly. Such observations support the notion
      that there are mechanisms, beyond exchange, that contribute to meiotic
      segregation fidelity. Recent findings indicate that active centromere pairing is
      important for proper kinetochore orientation and consequently, segregation of non
      exchange chromosomes. Here we discuss the implications of these findings for the
      behavior of meiotic chromosomes.

PMID- 15467469
TI  - TRIP-Br links E2F to novel functions in the regulation of cyclin E expression
      during cell cycle progression and in the maintenance of genomic stability.
AB  - The TRIP-Br family of transcriptional regulators (TRIP-Br1 and TRIP-Br2) has been
      proposed to function at E2F-responsive promoters to integrate regulatory signals
      provided by PHD zinc finger- and/or bromodomain-containing transcription factors.
      To characterize the TRIP-Br "integrator" function(s), we have employed decoy
      peptides (*Br1 and *Br2) to antagonize the interaction between TRIP-Br1 or TRIP
      Br2 and the PHD zinc finger and/or bromodomain of other transcription factors.
      Antagonism of the TRIP-Br integrator function elicits anti-proliferative effects
      through the transcriptional downregulation of a subset of E2F-responsive genes in
      vivo, and induces aberrant cyclin E accumulation, leading to Geminin deregulation
      and caspase-3-independent cellular sub-diploidization. The observed cyclin E
      deregulation is attributed to the downregulation of Fbxw7, which encodes the Fbw7
      receptor subunit of the SCF(FBW7) ubiquitin ligase (E3) responsible for targeting
      cyclin E for proteolysis. Fbxw7 is identified herein as an E2F-responsive and
      TRIP-Br coregulated gene. Our results demonstrate a physiologic role for TRIP-Br
      in coupling E2F to novel functions in the regulation of cyclin E expression
      during cell cycle progression to ensure the proper execution of DNA replication
      and the maintenance of genomic stability.

PMID- 15467471
TI  - PPARgamma signaling: one size fits all?
AB  - Outcome of PPARgamma activation in cancer cells is not one-dimensional. PPARgamma
      signaling is dependent upon PPARgamma ligand affinity and binding
      characteristics, target cell context and interacting signaling networks.

PMID- 15467472
TI  - N-Terminal polyubiquitination of the ARF tumor suppressor, a natural lysine-less
      protein.
AB  - Ubiquitin-dependent proteolysis by proteasomes generally depends upon the
      conjugation of polyubiquitin chains to lysine epsilon-NH(2) groups within the
      targeted proteins. However, engineered lysine-less mutants of certain viral and
      cellular proteins can undergo polyubiquitination at their N-termini. Is N
      terminal polyubiquitination a physiologic process, and how many cellular proteins
      can be targeted for proteasomal degradation through this mechanism? Recent work
      indicates that the turnover of the endogenous lysine-less human ARF tumor
      suppressor protein and its mouse Arf counterpart (containing a single, non
      conserved lysine residue) is regulated in this manner.

PMID- 15467475
TI  - [Pancreatic Transplantation: 2. Surgical technique and post-operative
      complications].
AB  - Since the first pancreatic allograft in 1966, pancreatic transplantations have
      been performed by numerous surgical teams throughout the world. Initial results
      were disappointing with a high percentage of technical failures and rejection.
      Over-optimistic enthusiasm for islet-cell allografts also retarded the
      development of pancreatic transplantation. Despite this slow start, results of
      pancreatic transplantation from 1995 onward have been very satisfactory and
      equivalent to or even better than the results of other solid organ transplants.
      This success has been due to better graft selection, improved surgical techniques
      and preservation solutions, and especially to improvements in immunosuppressive
      protocols. More than 19,000 pancreatic transplantations have now been performed
      throughout the world including both combined kidney-pancreas transplantations and
      pancreas-only transplantations. The most satisfactory results occur in the
      setting of dialysis-dependent renal failure due to diabetes; simultaneous
      combined kidney and pancreas transplantation is performed with the total pancreas
      implanted into the bowel and with venous drainage into the portal system. The
      long-term risks and constraints of chronic diabetes with renal failure must be
      weighed against the risks of a complex surgical procedure, significant post
      operative complications, and the need for long-term immunosuppressive therapy.

PMID- 15467473
TI  - Cks1 is dispensable for survival in Saccharomyces cerevisiae.
AB  - Cks1 is a small, evolutionarily conserved protein that was identified due to its
      genetic interaction with the Cdc28 cyclin-dependent kinase. In S. cerevisieae,
      Cks1 has long been regarded as a protein essential for cell survival. Here, we
      describe the derivation of viable cks1 null cells. cks1 null cells are slow
      growing and exhibit a variety of phenotypes consistent with functions previously
      described for cks1 temperature-sensitive mutants. In addition, we uncovered
      additional phenotypes (including a meiotic defect, sensitivity to high salt and
      inositol auxotrophy), all of which are defects associated with mutations in genes
      involved in general transcription pathways.

PMID- 15467476
TI  - [Chronic anoperineal pain: diagnosis and strategy for evaluation].
AB  - Chronic anoperineal pain may result from diverse causes; a precise and
      painstaking diagnostic approach is necessary to avoid inappropriate treatments
      which may aggravate the situation. Advances in imaging and neurophysiologic
      testing have improved the ability to diagnose and differentiate coccydynia,
      pudendal neuralgia, and the pyriformis muscle syndrome. Other etiologies
      including anismus, the descending perineum syndrome, and the levator ani syndrome
      are discussed as well as psychologic ans somatic interactions.

PMID- 15467477
TI  - [Ventral hernia repair with retromuscular Dacron prosthesis].

PMID- 15467479
TI  - [Anterograde colonic irrigation (technique of Malone)].

PMID- 15467480
TI  - [Dysphagia lusoria].

PMID- 15467481
TI  - [Management of traumatic retroperitoneal hematoma].
AB  - Traumatic retroperitoneal hematoma (RPH) may arise from injury to bony
      structures, major blood vessels, and intestinal or retroperitoneal viscera. To
      categorize the management of RPH, the retroperitoneum may be divided into three
      zones. Zone 1 (central) extends from the esophageal hiatus to the sacral
      promontory. Zone 2 (lateral) extends from the lateral diaphragm to the iliac
      crest. Zone 3 (pelvic) is confined to the retroperitoneal space of the pelvic
      bowl. For the traumatized patient with RPH, laparotomy is mandated by persistent
      hemodynamic instability despite intensive volume replacement. The judgment of
      whether and when to explore the retroperitoneal hematoma is guided by the
      mechanism of injury (blunt or penetrating) and the location of the RPH. RPH
      localized to the upper central area (Zone 1) after penetrating trauma implies
      injury to the great vessels and always requires urgent surgical exploration. RPH
      in other zones should be evaluated by CT and/or angiography; ongoing hemorrhage
      may respond to therapeutic embolization.

PMID- 15467482
TI  - [Intestinal malrotation].

PMID- 15467484
TI  - [Rare complications of Meckel's diverticulum: 1. Giant Meckel's diverticulum].

PMID- 15467485
TI  - [Rare complications of Meckel's diverticulum: 2. Trans-anal protrusion of a
      Meckel's diverticulum].

PMID- 15467486
TI  - Role of lipid rafts in T cells.
AB  - The plasma membrane of T cells is made up of a combination of phospholipids and
      proteins organized as glycolipoprotein microdomains termed lipid rafts. The
      structural assembly of lipid rafts was investigated by various physical and
      biochemical assays. Depending on the differentiation status of T cells, the lipid
      rafts seclude various protein receptors instrumental for the early T cell
      signaling, cytoskeleton reorganization, protein and membrane trafficking, and the
      entry of infectious organisms into the cells. This review article summarizes
      recent information on the assembly of lipid rafts in plasma membrane of T cells
      and their signaling output in mature and thymic precursors towards cell growth
      and differentiation, and possible modalities by which the function of lipid rafts
      can be altered by drugs and T cell ligands. The concept of using lipid rafts as a
      target for pharmaceutical compounds and biological T cell ligands to ultimately
      alter the T cell function is discussed.

PMID- 15467487
TI  - Rethinking oxidized low-density lipoprotein, its role in atherogenesis and the
      immune responses associated with it.
AB  - Atherosclerosis is a chronic inflammatory disease, resulting from hyperlipidemia
      and a complex interplay of many environmental, metabolic, and genetic risk
      factors. The unregulated macrophage uptake of cholesterol and lipids through
      modified forms of low-density lipoprotein (LDL), such as "OxLDL", transforms
      macrophages into "foam cells" to form the initial morphological lesion (the fatty
      streak). The modification of LDL not only enhances its uptake by macrophages, but
      also changes the natural structures of these otherwise ubiquitous molecules to
      generate a variety of modified lipids and proteins that represent highly
      immunogenic neo-determinants. For example, in ApoE-/- mice, autoantibody titers
      to epitopes on OxLDL are correlated with the extent of atherosclerosis.
      Similarly, oxidative stress on cellular membranes could also give rise to
      "oxidation-specific" epitopes and common autoantibodies. However, OxLDL is not
      uniform, but rather contains complex structures, ranging from a small
      conformational change in surface lipids to the breakdown of the peptide chain.
      Therefore, the immune responses to the variety of OxLDL and their association to
      atherosclerosis progression are very different. For example, phosphorylcholine
      (PC) is a natural component of phospholipids and exists in LDL and plasma
      membranes. "Natural" antibodies against PC can distinctively react to PC on
      bacteria, OxLDL and apoptotic cells, but not to those on unoxidized
      phospholipids, native LDL and viable cells, which suggests the broader role of
      such autoantibodies in maintaining the homeostasis of the host. While
      malondialdehyde-modified structures resemble more the exogenous changes and
      associate with advanced stage of lesion, they are more likely to associate with
      adaptive immunity.

PMID- 15467488
TI  - Polymorphisms within the genes encoding TNF-alpha and TNF-beta associate with the
      incidence of post-transplant complications in recipients of allogeneic
      hematopoietic stem cell transplants.
AB  - Hematopoietic stem cell transplantation (HSCT) is a curative treatment of many
      hematological disorders. Recent studies have shown the associations between
      polymorphic features of cytokine-encoding genes and the incidence of post
      transplant complications in the recipients of allogeneic HSCT. This review
      focuses on the relationship between the polymorphic patterns of patient genes
      encoding tumor necrosis factor (TNF)-alpha and TNF-beta and the manifestation of
      post-transplant complications, acute graft-versus-host disease (aGvHD),
      generation of toxic lesions, and mortality. Discussed in more detail are the
      relationships of TNFd microsatellites and polymorphisms within the promoter
      region of the TNF-alpha-encoding gene (TNFA in the position (-308) and within the
      first intron of the TNF-beta-encoding gene (TNFB). It appeared that
      heterozygosity within the TNFA promoter and the first intron of the (TNFB). It
      gene increased the susceptibility to severe grades III-IV of toxic complications,
      while the presence of the TNFd3 homozygous genotype was associated with a higher
      risk of severe aGvHD and early mortality in patients after allogeneic HSCT. These
      results imply that donor-recipient genotyping, extended to cytokine loci, may be
      of prognostic value for transplantation outcome.

PMID- 15467489
TI  - The role of PTEN in allergic inflammation.
AB  - Bronchial asthma is a chronic inflammatory disease of the airways, characterized
      by airway eosinophilia, goblet cell hyperplasia with mucus hyper-secretion, and
      hyper-responsiveness to inhaled allergens and to non-specific stimuli. Eosinophil
      accumulation and subsequent activation in bronchial tissues play critical roles
      in the pathophysiology of bronchial asthma. Many inflammatory mediators attract
      and activate eosinophils via signal transduction pathways involving an enzyme
      phosphatidylinositol 3-kinase (PI3-kinase). Studies using wortmannin, a specific
      inhibitor of PI3-kinase, have revealed the involvement of PI3-kinase in the
      biochemical transduction of activation signals generated by many inflammatory
      mediators in eosinophils. Wortmannin prevents the development of airway
      inflammation, either by inhibiting the eosinophil infiltration of bronchial
      tissues or their activation on arrival. Phosphatase and tensin homologue deleted
      on chromosome 10 (PTEN) is part of a complex signaling system that affects a
      variety of important cell functions. PTEN opposes the action of PI3-kinase by
      dephosphorylating the signaling lipid phosphatidylinositol 3,4,5-triphosphate.
      Recently we have demonstrated that PTEN expression is diminished in airway
      epithelial cells of antigen-sensitized and -challenged mice. Administration of
      PI3-kinase inhibitors or adenoviruses carrying PTEN complementary DNA remarkably
      reduces eosinophil levels and inflammation. One likely mechanism for this
      reduction is PTEN-mediated eosinophil degranulation and suppression of
      interleukin (IL)-4 and IL-5. These findings indicate that use of PTEN may be a
      good therapeutic strategy for the management of allergic inflammation.

PMID- 15467490
TI  - Mouse Ly-6 proteins and their extended family: markers of cell differentiation
      and regulators of cell signaling.
AB  - The Ly-6 locus on mouse chromosome 15 encodes a family of 10-12 kDa proteins that
      are linked to the cell surface by a glycosylphosphatidyl-inositol anchor and have
      cell signaling and cell adhesion properties. Expression of Ly-6 proteins is
      tightly regulated during development; these proteins continue to serve as
      excellent differentiation surface markers on normal and abnormal cells, but their
      role in driving cellular differentiation is still emerging. Recent studies
      suggest that Ly-6 gene products participate in regulating signaling through other
      cell type-specific receptors, perhaps by virtue of these proteins being localized
      in lipid rafts that play a key role in relaying signals from the membrane to the
      nucleus. Ligands for some Ly-6 proteins have been reported; the consequence of
      their interactions with the Ly-6 receptor remains to be fully uncovered. Mouse Ly
      6-like proteins have also been reported from a variety of life forms ranging from
      Caenorhabditis elegans to humans that show a limited amino acid identity and
      share structural features with members of mouse Ly-6. Despite these similarities,
      the non-murine Ly-6 proteins bind distinct ligands and appear to have different
      cellular functions. All members of the Ly-6 super gene family perhaps evolved
      from an ancestral gene by a gene duplication mechanism.

PMID- 15467491
TI  - The common gammac-cytokines and transplantation tolerance.
AB  - Transplant rejection, like tolerance, is a T cell-dependent event. There is
      compelling evidence to suggest that induction of transplant tolerance is an
      actively learned process in which T cells need to engage the alloantigens in
      order to learn to tolerate the allograft. A family of cytokines whose receptors
      use the same IL-2 receptor gamma chain (also called the common gammac) plays an
      important role in regulating multiple aspects of the allograft response (i.e.
      rejection vs. tolerance). It is undeniable that gammac-cytokines can drive clonal
      expansion and effector maturation of alloreactive T cells, and therefore,
      targeting such cytokines or their receptor components remains an attractive way
      of blocking transplant rejection. However, we just started to appreciate that
      gammac-cytokines also regulate the acquisition of transplant tolerance via
      programming activated T cells for apoptotic cell death and via guiding the
      evolution of regulatory T cells. Thus, understanding precisely the role of gammac
      cytokines in regulating T cell homeostasis and T cell regulation is critically
      important in the induction of transplant tolerance.

PMID- 15467492
TI  - Antichlamydial antibodies in the serum and expressed prostatic secretion in
      prostatitis.
AB  - INTRODUCTION: The aim of the study was to evaluate the prevalence of anti
      Chlamydia trachomatis (C.trachomatis) antibodies in serum and expressed prostatic
      secretion (EPS) in chronic prostatitis. MATERIALS AND METHODS: Thirty-six
      patients with chronic prostatitis were examined. The presence of C. trachomatis
      was determined in urethral smears and EPS. Specific antibodies were determined in
      the serum (IgM, IgA, IgG) and in the EPS (IgA, IgG). In the direct diagnosis of
      chlamydial infection, the direct immunofluorescence method and the ligase chain
      reaction were employed, and for the serological diagnosis, the immunoenzymatic
      method. RESULTS: C. trachomatis infection was detected in the urethra of 3 (8.3%)
      patients and in the prostatic gland of 3 (8.3%) patients; only one of these
      patients was found to have C. trachomatis in both the urethra and the EPS. In the
      control group, C. trachomatis was detected in the urethra of 1/50 (2%) of the
      men, but the EPS of all of them was free of C. trachomatis. Specific IgM
      antibodies were found in 7 (19.4%), IgA in 9 (25%), and IgG in 18 (50%) of the
      patients' serum, whereas IgAs were detected in 12 (33.3%) and IgGs in 13 (36.1%)
      of the patients' EPS. In the control group, anti-C. trachomatis antibodies of the
      IgG were detected in the serum of 2/35 (5.7%) of the men, whereas in the EPS
      neither IgA nor IgG antibodies were detected in any of these patients.
      CONCLUSIONS: Serological tests of the serum and EPS are useful as a complementary
      method in the diagnosis of chronic prostatitis.

PMID- 15467493
TI  - Oxidative modification of type II collagen differentially affects its
      arthritogenic and tolerogenic capacity in experimental arthritis.
AB  - INTRODUCTION: Oxidative modification of proteins affects their biological
      properties. Previously we have shown that hypochlorite (HOCl), the product of
      activated neutrophils, enhances protein immunogenecity. Collagen type II, a
      primary component of cartilage, is commonly used in the induction of arthritis in
      animals (CIA). The aim of this study was to examine whether HOCl may affect
      immunogenic, tolerogenic, and arthritogenic properties of collagen. MATERIALS AND
      METHODS: DBA/J mice were injected with either native (CNAT) or chlorinated
      collagen (CHOCl) to induce arthritis. The effect of chlorination on collagen
      properties was measured by evaluation of incidence and severity of CIA. Moreover,
      the concentration of serum anti-collagen IgG antibodies and myeloperoxidase (MPO)
      activity in inflamed joints was determined. RESULTS: Mice immunized with CNAT in
      adjuvant developed arthritis (CIA) with an incidence of 69%. CNAT also exerted
      tolerogenic properties when injected intravenously either before or shortly after
      primary immunization, resulting in decreased incidence and severity of CIA,
      reduced MPO activity in inflamed joints, and lowered serum levels of anti-CNAT
      IgG anti-bodies. Chlorination of collagen significantly diminished its ability to
      induce CIA and to trigger generation of anti-CNAT IgG antibodies. Interestingly,
      chlorination did not affect tolerogenic properties of collagen administered prior
      to primary immunization with CNAT. CONCLUSIONS: These results suggest that
      chlorination of collagen may selectively affect functional epitopes of collagen.
      It is likely that in inflamed joints, neutrophil derived HOCl, in some
      circumstances, will destroy arthritogenic and immunogenic B cell epitopes, while
      regulatory T cell epitopes will be preserved.

PMID- 15467495
TI  - Quality of post-anesthetic care in a hospital without a Post-Anesthetic Care
      Unit. A clinical audit.
AB  - AIM: The majority of Italian hospitals are not equipped with a Post- Anesthetic
      Care Unit. The aim of this study is to evaluate whether it is possible to
      guarantee post-anesthetic care according to current international quality and
      safety standards in the absence of such a structure. METHODS: Our hospital is not
      equipped with a Post-Anesthetic Care Unit and post-anesthetic assistance is
      assured by the anesthetist and anesthetic nurse themselves. In order to evaluate
      the quality of the post-anesthetic care a Recovery Chart was devised and strict
      discharge criteria defined: Recovery Score (modified Aldrete's score) = or >7;
      systolic blood pressure within 20% of the preoperative values; nausea/vomiting
      and shivering absent; pain absent/mild. A retrospective audit was conducted in 2
      orthopedic operating rooms from January 10, 2000 to January 31, 2001 in order to
      evaluate major complications, observance of discharge criteria, postanesthetic
      care time. RESULTS: Incidence of complications was 2.6%. Observance of discharge
      criteria was 74%. In 26% of cases (69/261 cases) discharge criteria were not
      completely respected: 14 cases with unstable vital parameters; 46 cases with pain
      not under control; 6 cases with nausea/vomiting; 3 cases with shivering. In these
      cases monitoring and treatment was continued on the ward according to the
      anesthetist's prescriptions. None of these patients died or suffered major
      complications because of a quick discharge to the ward. Mean post-anesthetic care
      time was 40+/-18 minutes (median 35 minutes). CONCLUSION: Where the Post-
      Anaesthetic Care Unit is not available it is virtually impossible to guarantee
      post-anesthetic care according to current international quality and safety
      standards, because production pressure can lead the anesthetist to discharge the
      patient to the ward before he/she is completely stabilized. In these cases the
      anesthetist must accurately prescribe the necessary postoperative monitoring and
      treatment (analgesics, antiemetics, fluids, etc.) that must be continued in the
      surgical ward to guarantee the patient's safety, but it must be underlined that
      the surgical ward is not the appropriate place to carry on immediate post
      anesthetic care.

PMID- 15467494
TI  - Sciatic nerve block with lateral popliteal approach for hallux vagus correction.
      Comparison between 0.5% bupivacaine and 0.75% ropivacaine.
AB  - AIM: In this study the authors compared the clinical profile of 2 local
      anesthetic drugs in the sciatic nerve block used during hallux valgus correction,
      a surgical procedure known to be post-operatively extremely painful. Since hallux
      valgus correction is painful post-operatively, many attempts have been tried to
      ensure a long-lasting analgesia. Block of the sciatic nerve appears to be the
      right choice balancing ease to performance, satisfaction of the patient and
      duration of action. METHODS: The authors investigated the use of 20 ml of 0.5%
      bupivacaine or 0.75% ropivacaine regarding the speed of onset, quality and length
      of duration of sciatic nerve block performed with a lateral popliteal approach.
      Sixty ASA I-III patients (aged 19-73 years) were enrolled in this trial. Written
      informed consent was asked and obtained. A 20 G 50 mm Teflon coated Crawford
      needle, delivering 0.5 mA at 2 Hz, was used to locate and block the sciatic nerve
      in the popliteal fossa with a lateral approach. RESULTS: Patients in the
      ropivacaine group required about 13 minutes to achieve a complete block and about
      16 minutes were needed in the bupivacaine group for the anesthesia to be
      complete. The length of analgesia was 16 h for the ropivacaine group and 13 h for
      the bupivacaine group. This kind of approach to block the sciatic nerve appeared
      to the authors to be very easy to perform, with the patient lying in a natural
      position. Surgical anesthesia required less than 30 min in both groups to be
      ready, while the ropivacaine group had a longer length of analgesia compared to
      the bupivacaine group. CONCLUSIONS: Patient satisfaction was high in both groups.

PMID- 15467496
TI  - Epidural analgesia for labour and delivery. Current evidence.
AB  - Currently, evidence-based medicine indicates that epidural analgesia (EA) labor
      is not associated with cesarean and instrumental delivery for dystocia. This
      evidence was obtained from clinical investigations of variability in clinical
      labor management. An optimized balance between anesthesiological and obstetric
      practice is vitally important for securing spontaneous delivery. The total dose
      of local anesthetic for EA may be associated with operative delivery when there
      is a lack of obstetric care standardization and co-interventions reducing
      unintended EA effects. Furthermore, combining local anesthetic low dose and
      opioid low dose may produce a new balance with obstetric management.
      Physiological and pharmacological knowledge together with recent clinical
      findings suggest that combined opioid-local anesthetic low dose EA causes minimal
      negative effects on labor progress and is effective and safe in terms of maternal
      and neonatal outcome. Internal communication between obstetricians and
      anesthesiologists is essential for optimizing EA labor management. Processes of
      health care quality management, such as medical audit and peer review, should be
      routinely practiced to reach this goal.

PMID- 15467497
TI  - Tracheomalacia associated with Mounier-Kuhn syndrome in the Intensive Care Unit:
      treatment with Freitag stent. A case report.
AB  - Tracheomalacia is a process characterized by softness of the supporting tracheal
      cartilages, by the extension of the posterior membranous wall and by reduction of
      the tracheal antero-posterior diameter. Exceptionally, tracheomalacia can be
      associated with tracheobronchomegaly or Mounier-Kuhn syndrome. Fibro-bronchoscopy
      represents the ''gold standard'' for diagnosis. The case of a 79-year-old male
      observed after hospitalization in a medical ward for chronic pulmonary
      obstructive disease (COPD) decompensation, and with basal left bronchopulmonary
      focus, is described. During this period, a progressive worsening of clinical
      conditions occurred, despite cortisone and antibiotic therapy, and the patient
      was transferred to the ICU for dyspnea, hypoxia, hypocapnia and with a diagnosis
      of pulmonary fibrosis. Bronchoscopy, performed during spontaneous breathing,
      revealed tracheomalacia which was responsible for tracheal dynamic complete
      stenosis during expiration and dynamic subtotal stenosis of the left primary
      bronchus in the first tract, together with sputum retention. Moreover, this
      investigation confirmed the diagnosis of tracheobronchomegaly already seen on CT.
      It was suggested to place a Freitag stent, since the insertion of another model
      would not have had enough chance of stability, due to the enormous extension of
      the tracheal lumen and could not have guaranteed good clearance of the
      secretions. Seven days after this intervention, performed in an outpatients'
      setting, the patient was dismissed from the ICU, without the help of O2, with
      good ventilation, saturation in line with his age and good expectoration.

PMID- 15467498
TI  - Immediate postoperative pain management in patients undergoing major abdominal
      surgery after remifentanil-based anesthesia: sufentanil vs tramadol.
AB  - AIM: The transition from intraoperative analgesia to postoperative analgesia must
      be planned carefully after remifentanil-based anesthesia, due to the short
      duration of action of remifentanil. The aim of this study is to compare the
      efficacy and safety of 2 transition strategies using sufentanil or tramadol for
      early postoperative pain relief in patients who had major abdominal surgery under
      general anesthesia with remifentanil/sevoflurane. METHODS: Sixty patients
      participated in this double-blind, prospective study and were randomly assigned
      to either sufentanil (S) group or tramadol (T) group. Twenty minutes before the
      end of surgery the patients received either a bolus of 0.15 microg kg(-1)
      sufentanil (group S) or tramadol 100 mg (group T). Mean arterial pressure (MAP),
      heart rate (HR) and rate pressure product (RPP=systolic arterial pressure
      (SAP)xHR), analgesia by a verbal rating score (VRS) and sedation by a sedation
      score (SS) were evaluated at emergence from anesthesia. RESULTS: A statistically
      significant difference in HR between the 2 groups was recorded at extubation
      (78+/-13 in group S vs 86+/-24 in group T). A significant decrease of RPP values
      at extubation and 5 minutes later were found in group S in comparison with group
      T. VRS values were significantly lower in sufentanil group at 5 and 10 minutes
      after awakening. CONCLUSIONS: Sufentanil provided more effective transition
      analgesia in comparison with tramadol. The effects of remifentanil dissipated
      rapidly and analgesia with major opioids was required. A bolus dose of sufentanil
      0.15 microg kg(-1) was efficacious in controlling the hemodynamic parameters at
      awakening from anesthesia. The lower HR values and, consequently the lower RPP
      values are of utmost importance especially in the aged cardiovascular risk
      patient.

PMID- 15467499
TI  - Role of sodium in dialysis.
AB  - The total amount of sodium present in the body conditions the extracellular
      compartment volume. In advanced renal failure and in dialysis the sodium balance
      becomes positive and the extracellular volume inflates. This leads to
      hypertension and to direct cardiac and vascular changes that explain for a large
      part the excessive cardiovascular morbidity and mortality in dialysis patients.
      Controlling body sodium content and extracellular volume allows to reduce
      hypertension, cardiovascular changes and to improve dialysis patients survival.
      This can be achieved by reducing the sodium input (low sodium diet and reasonably
      low sodium dialysate) and/or by increasing sodium output (ultrafiltration by
      convection in hemodialysis or hemofiltration and osmotic drive in peritoneal
      dialysis). The intermittent nature of hemodialysis (and hemofiltration)
      conditions the saw-tooth volume fluctuations that drove to conceiving and
      implementing the concept of a dry weight, corresponding to normal extracellular
      volume and blood pressure.

PMID- 15467500
TI  - Sorbents in the treatment of renal failure.
AB  - Standard renal replacement therapy in acute renal failure (ARF) and end-stage
      renal disease (ESRD) is based on membrane technology. The transition from natural
      cellulosic membranes to synthetic membranes has not been associated with
      improvement in mortality rates. Modifications of dialysis with continuous
      arteriovenous hemofiltration and hemodiafiltration to remove middle molecular
      weight toxins, low molecular weight proteins and peptides (LMWP) and cytokines
      involved in inflammation appear to have reached their limits. High flux dialyzers
      are not efficient at removing LMWP and for this reason sorbents to augment or
      replace dialysis have been used in clinical trials. Removal of LMWP such as beta2
      microglobulin, leptin, complement factor D, angiogenin, and cytokines such as IL
      1, IL-6, IL-10, IL-18 and TNFalpha, have been established in animal models of
      sepsis, and in ESRD patients using sorbents in conjunction with high flux
      dialysis. Sorbent devices added to hemodialysis, or alone in inflammatory states,
      are being studied in diseases which possess a common pathway of systemic
      inflammatory response syndrome; these states are sepsis, ARF, cardio-pulmonary
      bypass, in brain dead subjects prior to explantation of donor organs and ESRD.

PMID- 15467501
TI  - Current topics on vascular access for hemodialysis.
AB  - Vascular access remains the lifeline for end-stage renal failure patients, which
      have been treated by chronic intermittent hemodialysis. Due to the steady
      increase in the number of patients with difficulties to create access, in
      particular in elderly with various comorbidities, the need for more insight and
      regulations have evolved into the publications of the American and European
      guidelines. From the latter it may be obvious that an adequate preoperative
      assessment followed by the creation of autogenous arteriovenous fistulas (AVFs)
      is far better and preferred to the implantation of grafts. Vascular access
      maintenance by monitoring and elective percutanuous or surgical revision is of
      utmost importance to keep the access site functional. Despite up-to-date measures
      for vascular access maintenance, various complications may treaten not only the
      access site but also quality and expectance of life. Thrombotic occlusion remains
      a major event, leading to permanent failure in 10% of AVFs and 20% of grafts each
      year. Interventional (percutaneous transluminal angioplasty and/or stent
      implantation) or surgical revision of thrombosed accesses have similar outcomes
      with a high rate of reinterventions. The elderly diabetic population with
      peripheral arteriosclerotic obstructive disease is in particular prone to angio
      access induced handischemia. When not timely and properly treated this may lead
      to minor or major amputation, further hampering quality of life. Also, the
      enormous application in the past 2 decades of acute central venous lines has lead
      to a significant increase of central venous obstruction with concomittent
      morbidity and problems creating vascular access in the upper extremities.
      Radiological intervention in these cases is a primary option, leaving surgical
      reconstruction as a second best method. It may be obvious that creation and
      maintenance of hemodialysis vascular access has become an important and time
      consuming speciality. Only an up-to-date multidisciplinary management with
      involvement of nurses, nephrologists, interventionalists and surgeons, will lead
      to the desired outcome.

PMID- 15467502
TI  - Systemic inflammation in dialysis patients with end-stage renal disease: causes
      and consequences.
AB  - Despite rapid improvements in dialysis technology during the last 20 years, the
      mortality rate in end-stage renal disease (ESRD) patients treated with dialysis
      is still unacceptably high and comparable to that of many cancer patients with
      metastases. The main cause of the increased mortality in ESRD patients is
      cardiovascular disease (CVD), which is twice as common and advances at twice the
      rate already in patients with earlier stages of chronic kidney disease as
      compared to the general population. Although traditional risk factors are common
      in dialysis patients, they can only in part explain the very high prevalence of
      CVD in this patient group. Recent evidence demonstrates that chronic
      inflammation, a non-traditional risk factor which is a commonly observed in
      dialysis patients, may cause malnutrition and progressive atherosclerotic CVD by
      several pathogenetic mechanisms. Available data suggest that pro-inflammatory
      cytokines play a central role in the genesis of both malnutrition and CVD in
      ESRD. While the long-term effects of chronic inflammation may be most important
      in the pathogenesis of CVD, the acute-phase reaction may also be a direct cause
      of acute vascular injury by several pathogenetic mechanisms. The cause(s) of
      inflammation in dialysis are multifactorial and include both dialysis-related and
      unrelated factors. Thus, it could be speculated that suppression of the vicious
      cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would
      improve survival in dialysis patients. As there are currently no established
      guidelines for the treatment of chronic inflammation in ESRD patients, studies on
      the long-term effects of various anti-inflammatory treatment strategies on the
      nutritional and cardiovascular status as well as outcome in this patient group
      are warranted.

PMID- 15467503
TI  - Epidemiology and clinical significance of hepatotropic infections in dialysis
      patients. Recent evidence.
AB  - Hepatitis C virus (HCV) infection is frequent among patients receiving long-term
      dialysis in developed and developing countries. It is difficult to assess the
      natural history of HCV in the dialysis population; however, recent studies have
      demonstrated that positive anti-HCV status is a significant and independent risk
      factor for mortality among dialysis patients. Recent meta-analyses have shown
      that interferon (IFN) initial monotherapy is effective in the treatment of
      chronic hepatitis C among dialysis patients, but tolerance to IFN mono-therapy
      was rather poor. Large, multicenter and prospective trials based on pegylated IFN
      for the treatment of chronic hepatitis C are planned. The frequency of HBV
      infection in patients undergoing maintenance dialysis in the industrialized world
      is low but not negligible; persistent HBsAg seropositivity is much higher in less
      developed countries. Recent surveys have shown that detectable HBsAg/ HBV DNA
      status in serum is an independent and significant predictive factor for
      hepatocellular dysfunction in dialysis patients. No significant difference in
      morbidity and mortality between dialysis patients according to hepatitis B
      surface antigen status has been consistently shown. Preliminary reports suggest
      that lamivudine appears to be safe and effective in patients receiving long-term
      dialysis.

PMID- 15467504
TI  - Infections related to prosthetic materials in patients on chronic dialysis.
AB  - Access to dialysis is the most infection prone part of any dialysis system. The
      prophylactic management of the exit site, the various access systems and their
      role in infections is discussed. Methods are suggested to avoid or control
      infections.

PMID- 15467505
TI  - Daily haemodialysis in acute renal failure. Old wine in a new bottle?
AB  - Acute renal failure (ARF) is a frequent complication in hospitalized patients.
      Despite advances in intensive care and renal replacement therapy, outcomes in ARF
      are distressingly poor. The high mortality of critically ill patients with ARF
      relates at least in part to fatal non-renal organ complications of ARF itself.
      However, adequacy of dialysis therapy in the setting of ARF is still in its
      infancy. At present, neither for intermittent haemodialysis (IHD) nor continuous
      renal replacement therapies specifically designed techniques have been developed
      or validated to measure the delivered dose of in ARF. Furthermore targets of
      optimal or required dose have not been defined. Problems intrinsic to ARF that
      hinder accuracy of dialysis dose measurements utilizing urea kinetic modelling
      include a lack of urea eubolism, uncertainty about the true patient total water
      volume and volume of distribution of urea, and significant access recirculation.
      The difference in prescribed versus delivered dialysis dose in patients with ARF
      undergoing IHD may exceed 20% and more and the majority of ARF patients will
      receive dialysis doses less than 1.2, which is considered the minimal level for
      end-stage renal disease patients undergoing regular dialysis. Nonetheless
      retrospective data from the Cleveland Clinic clearly demonstrate an influence of
      delivered Kt/V urea on survival in patients with intermediate ICU ARF severity
      scores. Our group prospectively compared outcomes in patients with ARF receiving
      IHD daily or on alternate days. Daily HD was associated with fewer dialysis
      related hypotensive episodes, a shorter time and smoother course to recovery of
      renal function and a significantly reduced mortality compared to conventional HD.
      This article highlights also the facts that patients in the conventional group
      (the standard treatment in North America) treated every other day for 3 to 5
      hours have been inadequately dialyzed, having a mean blood urea nitrogen (BUN) of
      104 mg/dl and significantly more respiratory failure, sepsis, gastrointestinal
      bleeding or changes in mental status. To avoid significant underdialysis,
      conventional estimates of total body water should be increased by a factor of
      1.2. Strategies associated with improved outcomes that have emerged thus far in
      ARF should aim at a time-averaged BUN of less than 60 mg/dl with IHD. IHD should
      be prescribed in varying frequency if necessary with daily sessions in
      hypercatabolic oliguric or heavy weight critically ill patients.

PMID- 15467506
TI  - Cardiovascular disease in renal failure.
AB  - Cardiovascular disease is prevalent in patients with chronic kidney disease and
      may account for 50% of all deaths. Left ventricular hypertrophy is the most
      frequent cardiac alteration in end-stage renal disease (ESRD) patients. It is due
      to a combination of hemodynamic and humoral factors. Volume overload and pressure
      overload are responsible for adaptative alterations of the heart and the vessels
      consider as a unique functional system. These alterations are first beneficial
      but their persistence leads to a detrimental process, mainly cardiac dilation and
      failure. Treatment of the hemodynamic overload could partially stabilize or
      reverse this evolution.

PMID- 15467507
TI  - Diabetes mellitus and dialysis.
AB  - Diabetes mellitus is increasing, and in some countries is the single most
      important cause, for end-stage renal disease. In general, primarily elderly
      patients on renal replacement therapy, are not only affected by diabetes-related
      long-term complications, but also frequently with a wide range of co-morbidities.
      Apart from cardiac complications, the patients are subject to a wide range of
      vascular (i.e. peripheral vascular disease, stroke) and infectious complications.
      In the past this has been reflected by a relatively poor survival rate on
      dialysis, and minimized chances to obtain renal transplantation. Today, several
      renal replacement strategies are available, including the main 3: hemodialysis,
      peritoneal dialysis or kidney transplantation. For patients with diabetes
      mellitus, hemodialysis is the most commonly used therapy. Each dialysis unit
      should achieve an optimal dialysis adequacy represented by a single pool Kt/V of
      at least 1.2. The most important independent predictor of patient survival with
      hemodialysis treatment is age. Other factors related to complications are left
      ventricular hypertrophy, arterial hypertension, hypervolaemia and chronic anemia.
      Moreover, medial arterial calcification, malnutrition, gastrointestinal disorders
      and dialysis against low potassium dialysate are related to increased morbidity
      and mortality as well. An integral part of treatment is the availability of good
      vascular access. The survival rates of fistulas show a nearly twofold higher rate
      of failure for synthetic grafts compared with arteriovenous fistulas. The role of
      peritoneal dialysis in renal replacement therapy in patients with diabetic
      nephropathy is well established and used world-wide. Most patients with residual
      renal function start with continuous ambulatory peritoneal dialysis (CAPD), but
      automated peritoneal dialysis can also be used. An unresolved problem associated
      with CAPD is the glucose absorption and caloric intake. The optimum adjustment of
      blood glucose values is made more difficult. Death rates of diabetic patients on
      peritoneal dialysis remain higher than in non-diabetics. The changes in
      peritoneal membrane thickness and vascular alterations in relationship to the
      duration of dialysis are caused mainly by glucose and glucose degradation
      products, such as advanced glycation endproduct (AGEs). Therefore, new peritoneal
      dialysis solutions are needed to reduce the complications and to delay a long
      time function of the peritoneal membrane. Peritonitis remains still the major
      cause of discontinuation of dialysis but there is no increased risk in diabetic
      patients. Nevertheless, an integrative care of end-stage renal disease patients
      with diabetic nephropathy should be offered to the patient, starting on
      peritoneal dialysis and switch to hemodialysis if problems arise. During the
      whole time patients should be kept on the renal transplantation waiting list.

PMID- 15467508
TI  - Dialysis in the elderly. New possibilities, new problems.
AB  - In the last 2 decades, there has been a phenomenal increase in the number of
      incident and prevalent elderly patients receiving renal replacement therapy (RRT)
      and this trend is likely to continue. This article reviews the changing
      demographics of the renal patient population and discusses the possible reasons
      for this. The profile of the older adult patient group is discussed, and specific
      demands and requirements of this patient group are explained. In particular, the
      authors concentrate on dialysis mode and vascular access; malnutrition; falls and
      fractures; cognitive impairment and depression and drugs and pain. It is clear
      that the ''old old'' can benefit significantly from dialysis despite an
      increasing burden of comorbidity and prognosis on dialysis is discussed. In order
      to properly inform patients about treatment options it is essential to provide
      information about prognosis. For some patients dialysis may not be the preferred
      option and for others withdrawal from dialysis may be appropriate. Nephrologists
      therefore also need to be familiar with end of life issues and palliative symptom
      control.

PMID- 15467509
TI  - [Nephron sparing surgery].
AB  - AIM: The role of nephron sparing surgery in patients with a solitary kidney,
      bilateral kidney tumors or an impaired renal function has been widely accepted.
      Partial nephrectomy in patients with a normal contralateral kidney is still under
      discussion. METHODS: We evaluated the effectiveness and safety of the
      nephronsparing surgery in the treatment of low stage renal cell carcinoma versus
      radical nephrectomy. We evaluated the records of 12 patients with localized,
      symptomless small renal masses (<4 cm) treated with nephronsparing surgery (group
      A) and 12 patients matched for age, tumor location, size, and stage who were
      treated with radical nephrectomy (group B). RESULTS: The operations were
      successfully completed in all intended cases. No major bleeding or urine leakage
      from the enucleation bed was observed. None of the cases presented with
      postoperative bleeding or urine leakage from the enucleation bed. Severe
      impairment of the renal function was not observed in any case evaluated by means
      of serum creatinine and creatinine clearance. The overall survival rate was 100%
      without recurrence up to 24 months of the mean follow-up. CONCLUSION: Partial
      nephrectomy for small peripheral lesions is a safe procedure with low morbidity.
      No definite recurrences are evident at an early stage of follow-up, although
      longer review (probably more than 10 years) will be required to assess cancer
      specific survival following this procedure.

PMID- 15467510
TI  - Gross hematuria 10 years after radical cystectomy: adenomatous polyp.
AB  - Patients undergoing radical cystectomy with an ileal neobladder need intensive
      follow-up due to the recent studies concerning the potential neoplastic
      transformation of the intestinal mucosa. We report a case of a gross hematuria
      due to a lesion that developed in an ileal orthotopic bladder 10 years after a
      nerve and seminal sparing radical cystectomy for transitional bladder cancer. We
      performed a transurethral resection of the lesion and histopathological
      evaluation revealed an adenomatous polyp. In our case transurethral resection of
      the adenoma seems to be a safe and conservative approach in the management of
      these lesions, however further follow-up is requested.

PMID- 15467511
TI  - Genetics of human arterial hypertension.
AB  - Arterial hypertension is one of the major cardiovascular risk factors in Western
      countries. Besides some well established, but rather rare forms of secondary
      hypertension, essential hypertension is the most common diagnosis. The hereditary
      nature of this disease has been well established in many familial studies. The
      quantitative contribution of genetic factors to blood pressure variance is
      estimated to be about 30%, however, the genetic background of essential
      hypertension is complex and currently not fully understood. Besides few
      monogenetic forms of Mendelian transmitted hypertension, current efforts are
      usually directed at the identification of single contributing genetic factors.
      This review is thought to highlight current strategies towards a better
      understanding of the genetic background of essential hypertension with particular
      respect to genetic variants of the renin-angiotensin system, of signaling
      pathways such as heterotrimeric G-proteins and alpha-adducin. Moreover, genetic
      association studies often fail to replicate findings from previous studies. This
      may be in part due to the polygenetic nature of the disease. Another potential
      reason may be the diversity of the investigated populations. The current results
      of genetic analyses of essential hypertension highlight, thus, the need for a
      more differentiated approach to the understanding of complex, polygenetic traits
      implementing gene-gene-, and gene-environment interactions or distinguished
      functional testing of thoroughly phenotyped cohorts under standardised
      environmental conditions.

PMID- 15467513
TI  - Chronic kidney disease and global cardiovascular risk in essential hypertension.
AB  - Recently published guidelines recognize the relevance of the finding of chronic
      kidney disease (CKD) in the stratification of risk of the hypertensive patient.
      Determination of the presence of microalbuminuria and estimation of glomerular
      filtration rate are mandatory in order to ensure an adequate evaluation of global
      cardiovascular (CV) risk in the hypertensive patient. Indices of altered renal
      function (e.g. microalbuminuria, increased serum creatinine concentrations,
      decrease in estimated creatinine clearance or overt proteinuria) are independent
      predictors of CV morbidity and mortality. Clustering of associated risk factors
      seems to justify the elevated CV morbidity and mortality observed in patients
      with essential hypertension and mild alterations of renal function. The increased
      prevalence of CKD in the general and in the hypertensive populations forces the
      recognition of its relevance and the need for an integrative therapeutic approach
      to fully protect simultaneously renal and CV systems.

PMID- 15467512
TI  - Clinical insights into the diagnosis and management of renovascular disease. An
      evidence-based review.
AB  - Renovascular disease is a common, but complex disorder, the most common causes of
      which are fibromuscular dysplasia and atherosclerosis. It usually presents in 1
      of 3 forms: asymptomatic renal artery stenosis, renovascular hypertension, or
      ischemic nephropathy. The clinical index of suspicion remains paramount in
      developing an appropriate diagnostic strategy. Although subject to certain
      limitations, conventional contrast angiography is usually considered the gold
      standard in confirming the diagnosis. In addition, there are a number of
      available non-invasive tests that can aid in decision-making. These tests can be
      divided into those that detect the anatomic presence of a stenosis and those that
      identify the functional consequences of the renal artery obstruction. No one
      study is appropriate for every patient. Treatment options include medical,
      surgical or percutaneous approaches. Generally, in patients with fibromuscular
      disease the results of surgery and percutaneous approaches appear superior. In
      patients with atherosclerotic disease, the data are less consistent, and there
      does appear to be a group of patients who will respond well to medical
      management. Potential diagnostic algorithms for diagnosis and treatment are
      presented in this review.

PMID- 15467514
TI  - Diabetic nephropathy: implications for renal and cardiovascular outcomes.
AB  - Diabetic nephropathy is a disease entity that is becoming more prevalent in the
      developed world. Its effect on individuals and society is profound, both in terms
      of cost and on patient health, especially in relation to associated
      cardiovascular disease. This review is an analysis of the most recent data
      available on diabetic nephropathy and its clinical applications to patient care.
      Using Medline search for relevant data from 1983 to the present, it focuses on
      clinical strategies that are employed to help curtail the progressive nature of
      this disease. Current strategies, including glycemic control, blood pressure
      treatment, inhibition of the renin/angiotensin system, nutrition, and
      hyperlipidemia, are discussed in relation to the relevant clinical data. Current
      clinical markers and possible future treatments are also discussed in the context
      of aiming to improve clinical outcomes in patients who are affected.

PMID- 15467516
TI  - Stem cells and kidney diseases.
AB  - The role of the stem cell (SC) in physiology and physiopathology has recently
      attracted much interest. SCs may originate from embryos, aborted fetuses,
      umbilical cord blood, and adult organs and tissues. In the adult, SCs were first
      defined in tissues with a high cell turnover, like skin and gut. Today, SCs have
      also been identified in tissues with no or low regenerative potential and
      turnover. However, the SC concept is changing rapidly: adult SCs not only reside
      locally in specific niches, but may also be recruited from the circulation to
      actively participate in the regeneration of various tissues. Furthermore, reverse
      differentiation has been demonstrated. In the kidney, both glomerular and tubular
      cells may differentiate into a range of phenotypes during the remodelling process
      in response to injury. The glomerular and tubulointerstitial scarring processes
      involve primarily interactions between infiltrating inflammatory cells and
      resident renal cells that culminate in loss of renal cells and their replacement
      by extracellular collagenous matrix. Reverse embryogenesis is a key step in renal
      healing and scarring: intrinsic renal cells regress to primitive/embryonic
      mesenchymal phenotype. In addition, it is clear that renal remodelling in health
      and disease involves the migration of hematopoietic SCs into the kidneys. These
      cells assume various glomerular and tubular epithelial phenotypes. Therefore, a
      better understanding of some of these key events in renal remodelling may open
      the way to new interventions based on their manipulations. Cell-based therapy may
      be a more successful strategy by providing a dynamic and individualized
      therapeutic approach that responds to the physiopathological condition of the
      patient. In fact, SCs may provide innovative methods for drug delivery,
      immunotherapy, tissue regenerative or replacement engineering.

PMID- 15467515
TI  - Renoprotection by blockade of the renin-angiotensin-aldosterone system in
      diabetic and non-diabetic chronic kidney disease. Specific involvement of intra
      renal angiotensin-converting enzyme activity in therapy resistance?
AB  - Data of numerous clinical trials show that lowering of blood pressure is
      prerequisite for reducing the rate of renal function loss in chronic renal
      disease. There is evidence supporting that blood pressure lowering obtained by
      intervention in the renin-angiotensin-aldosterone system (RAAS) has an additive
      renoprotective effect over reduction of blood pressure alone, both in diabetic
      and non-diabetic renal diseases. The main evidence for renoprotective action of
      RAAS blockade is provided by its consistent antiproteinuric action, which cannot
      completely be attributed to the reduction in blood pressure. Indeed, proteinuria
      reduction during therapy is the single most important factor predicting the renal
      prognosis, independent from the class of drugs used. Yet, still patients progress
      to end-stage renal disease. In this review, individual differences in therapy
      response and possibilities to overcome therapy resistance to RAAS blockade are
      discussed. Experimental data from studies in rats suggest a specific involvement
      of intrarenal factors, particularly of preexisting renal damage and renal
      angiotensin-converting enzyme (ACE) activity, in therapy resistance.
      Identification of such factors in individual renal patients provides mechanisms
      by which renoprotective strategies fail to overcome therapy resistance. This
      prompts for a dual approach to improve renoprotection, namely unravelling these
      specific intrarenal mechanisms on the one hand, and development of better
      strategies for early detection of renal risk on the other hand.

PMID- 15467517
TI  - The pathophysiology of irritable bowel syndrome.
AB  - Recent studies have provided evidence to suggest a possible role for mucosal
      immune activation in the pathophysiology of irritable bowel syndrome (IBS). On
      the other hand, novel findings using functional brain-imaging techniques support
      the concept that altered perception of visceral stimuli plays a key role in IBS
      symptom generation. These seemingly contradictory findings have revived the
      discussion about the relative contribution of peripheral versus central
      mechanisms in the symptom generation of IBS. In this review, we will provide
      evidence for the hypothesis that, in the absence of changes in visceral
      perception and alterations in endogenous pain modulation systems, chronic
      inflammatory mucosal changes in the gut are not a plausible mechanism to explain
      the presence of chronic abdominal pain, a clinical hallmark of IBS.

PMID- 15467518
TI  - Diagnostic and therapeutic strategies in the irritable bowel syndrome.
AB  - The management of patients with irritable bowel syndrome (IBS) is a frequent, yet
      challenging task in both primary care and gastroenterology practice. A diagnostic
      strategy guided by keen clinical judgment should focus on positive symptom
      criteria and on the absence of alarm symptoms. In younger patients lacking alarm
      features, invasive testing has a low-yield. The presence of food intolerance and
      underlying celiac disease should be excluded. The usefulness of fecal tests such
      as calprotectin and lactoferrin to exclude organic bowel disease is not
      adequately established. In patients with moderate to severe symptoms who fail
      initial therapeutic trials, further tests can be performed in tertiary care
      settings, such as transit measurement and tests for diagnosing pelvic floor
      dysfunction. Treatment strategies for IBS are currently directed at the
      predominant symptoms. In diarrhea-predominant IBS, opioids (e.g. loperamide) and
      the 5-HT(3) receptor antagonist alosetron are efficacious. In constipation
      predominant IBS, fiber and bulk laxatives are traditionally used, but their
      efficacy is variable and may worsen symptoms. The 5-HT(4) receptor agonist
      tegaserod is efficacious in female patients with IBS and constipation. In
      patients with IBS and abdominal pain, antispasmodics and antidepressants can be
      used, with the best evidence supporting the prescription of tricyclic
      antidepressants. The efficacy of psychological treatments in terms of relieving
      the symptoms of IBS is still uncertain. Limited evidence suggests that anti
      enkephalinase agents, somatostatin analogues, alpha(2)-receptor agonists, opioid
      antagonists, selective serotonin reuptake inhibitors, probiotics and herbal
      treatments may be useful in IBS patients.

PMID- 15467519
TI  - Psychological influences on the irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is often considered as a purely psychosomatic
      condition. However, there is now good evidence that it is a multifactorial
      condition with a whole variety of influences leading to disease expression, of
      which psychological issues are only one. Nevertheless, addressing psychosocial
      problems forms an important part of the therapeutic approach to IBS. It is now
      known that ongoing social stress can make IBS refractory to treatment and there
      is increasingly firm data to support the notion that antidepressant
      pharmacotherapy and a variety of behavioural treatments, offer patients with more
      severe forms of the illness a chance of long-term improvement.

PMID- 15467520
TI  - [After the 2001 European Society of Cardiology Guidelines: is it possible to
      reduce the number of patients with syncope to be hospitalized?].
AB  - AIM: The aim of this paper was to evaluate how many patients with syncope should
      be hospitalized according to the 2001 European Society of Cardiology (ESC)
      Guidelines on the management of syncope. METHODS: Starting from August 2002 we
      prompted a Syncope Unit (SU), as a multi-disciplinary functional structure
      including the Emergency Department. One of the main objectives of the SU was the
      implementation of the 2001 ESC Guidelines on Syncope and of the relevant criteria
      for hospitalization. All the clinical data concerning the patients presenting
      with syncope were prospectively collected and stored in a dedicated database.
      RESULTS: Between September 1, 2002 and April 30, 2003, 402 patients were observed
      for a syncope. Out of these, 19 had a cardiogenic syncope, 3 focal neurologic
      disorders, 25 a severe trauma, 4 severe orthostatic hypotension and 5 carotid
      syncope. Therefore, 56 patients out of 402 were found to have indication to
      therapeutical hospitalization. Among the remaining 346 patients, 83 patients were
      found to have a structural heart disease and/or an abnormal ECG, 1 had syncope
      during exercise, 3 presented a familial history of sudden death. Thirty-three
      were found to have severe comorbidities and further 14 had occasional indication
      to hospitalization. Thus, 190 out of the 402 patients with syncope (47.3%)
      presented at least 1 criterion for hospitalization according to the ESC
      Guidelines. CONCLUSION: The implementation of the ESC Guidelines on Syncope is
      technically feasible. Nevertheless, even when the Guidelines are strictly
      observed, a high percentage of patients with syncope has still to be
      hospitalized. Our data suggest that new criteria should be established for a safe
      Emergency Department discharge of the patients with syncope, particularly of
      those with structural heart disease or abnormal ECG.

PMID- 15467521
TI  - Regional haemoglobin oxygen saturation during surgical haemorrhage.
AB  - AIM: Experimental research and early clinical studies have shown that regional
      haemoglobin desaturation, measured by near infrared spectroscopy (NIRS), follows
      blood loss. To further assess NIRS as a blood loss monitor, we evaluated it on
      patients undergoing major surgery. METHODS: Regional haemoglobin oxygen
      saturation from the cerebral cortex (CsO(2)) and the left gastrocnemius muscle
      (PsO(2)) was continuously monitored with an INVOS 4100 NIRS oximeter in 10
      patients during surgery. Haemoglobin, mean arterial pressure, arterial and
      central venous oxygen saturation and tension, temperature, pH and lactate
      concentration were also measured. RESULTS: The median (IQR) blood loss was 650
      (400-1 800) ml, equivalent to 16% (11-35) of the patients' blood volume. During
      surgery, CsO(2) fell by a mean (95% CI) of 8.4% (2-14.8) (p=0.016) and PsO(2)
      fell by a mean (95% CI) of 3.3% (-1.5-8.1) (p=0.16). CsO(2), but not PsO(2),
      correlated with the volume of blood lost (R=0.44; p=0.004), central venous oxygen
      saturation (R=0.52; p=0.001), and venous oxygen tension (R=0.58; p<0.001). These
      correlations remained significant after calculations were adjusted for changes in
      arterial pressure, temperature and pH. CONCLUSION: Cerebral, but not peripheral,
      haemoglobin oxygen saturation decreases proportionally to blood loss and
      correlates with measurements of systemic oxygen extraction. With further
      research, NIRS measurements of CsO(2) may be developed into a useful tool to
      monitor blood loss.

PMID- 15467522
TI  - Temporal kinetics of the light/dark translocation and compartmentation of
      arrestin and alpha-transducin in mouse photoreceptor cells.
AB  - PURPOSE: To determine the temporal kinetics of the simultaneous translocation of
      arrestin and rod alpha-transducin in mice exposed to different lighting
      environments and to compare the subcellular compartmentation of cone alpha
      transducin with arrestin. METHODS: Double labeling immunofluorescence microscopy
      and image analysis are used to visualize and quantify the concentrations of rod
      arrestin and alpha-transducin in the subcellular compartments of the rod outer
      segments, the rod inner segments and the synaptic terminals. RESULTS: The
      magnitude of the effects of the translocation are clearly contrasted in images of
      the retinas of animals that have been maximally light adapted verses retinas that
      have been maximally dark adapted. The onset of light results in a rapid,
      simultaneous, translocation of arrestin and alpha-transducin from their
      respective compartments (alpha-transducin in the rod outer segment and arrestin
      in the rod inner segment) to the opposite compartment. Almost all of alpha
      transducin has translocated in less than two min whereas the translocation of the
      majority of arrestin requires at least five to six min. Translocation in the
      opposite direction, from light to dark, occurs more slowly for both proteins with
      arrestin requiring almost 30 min and alpha-T needing more than 200 min to
      complete its journey. Under the same lighting conditions, cone arrestin
      translocation is incomplete. Cone alpha-transducin does not translocate under any
      the lighting conditions tested. Unlike the frog, continuous exposure of mice to
      light does not result in arrestin translocating back to the rod inner segment.
      CONCLUSIONS: These data suggest that there are four mechanisms involved in the
      translocation of these two proteins. They also support the conclusion that the
      more important cellular function of the translocation process is to terminate
      phototransduction in rod and cone photoreceptors, which could provide protection
      against light damage. The secondary function of translocation is to maximize rod
      sensitivity to light during dark adaptation. The restricted localization of cone
      alpha-transducin to the cone outer segment is consistent with the function of
      cones in bright light, just as the concentration of rod alpha-transducin in dark
      adapted rod outer segment is consistent with their functioning in dim light.

PMID- 15467523
TI  - Differential phosphorylation of connexin46 and connexin50 by H2O2 activation of
      protein kinase Cgamma.
AB  - PURPOSE: Fiber cell gap junction proteins connexin 46 (Cx46) and connexin 50
      (Cx50) play distinct roles in the avascular lens. The purpose of this study was
      to determine how protein kinase Cgamma (PKCgamma) differentially regulates
      phosphorylation of Cx46 and Cx50 in oxidatively stressed lenses. METHODS: Sprague
      Dawley rats (six week old) were used in the experiments. PKCgamma enzyme activity
      was analyzed by use of the PepTag assay kit. Phosphorylation of caveolin-1, Cx46,
      and Cx50 was determined by immunoblotting. Lipid rafts were isolated by
      continuous sucrose gradient centrifugation. Lipid raft-localization of PKCgamma,
      Cx46, or Cx50 was demonstrated by immunoblotting. Association of caveolin-1 with
      PKCgamma, Cx46, or Cx50 was revealed by co-immunoprecipitation. RESULTS: H2O2
      (100 microM) stimulated PKCgammaactivation in rat whole lens. Activated PKCgamma
      was recruited into caveolin-1 (Cav-1) containing lipid rafts and this activation
      enhanced the coimmunoprecipitation of Cav-1, Cx46, and Cx50 with PKCgamma. Both
      Cx50 and Cx46 were associated with Cav-1 in lipid rafts. H2O2 significantly
      induced threonine (Thr) phosphorylation of Cx46 and Cx50, and serine (Ser)
      phosphorylation of Cx50. However, There was only a small stimulation of Cx46
      phosphorylation at Ser by H2O2, as Cx46 was already phosphorylated. CONCLUSIONS:
      Activation of PKCgamma by H2O2 stimulated differential Ser phosphorylation of
      Cx50 versus Cx46, within lipid rafts. This suggests that Cx50 and Cx46 may have
      different functions in lens.

PMID- 15467524
TI  - A novel diagnostic test detects a low frequency of the hemicentin Gln5345Arg
      variant among Northern Irish age related macular degeneration patients.
AB  - PURPOSE: Age related macular degeneration (AMD) is a common cause of severe
      vision loss. Identification of genes involved in AMD will facilitate early
      detection and ultimately help to identify pathways for treatment for this
      disorder. The A16,263G mutation in the HEMICENTIN-1 gene produces a non
      conservative substitution of arginine for glutamine at codon 5345 which has been
      implicated in familial AMD. The aim of this study is to develop a rapid
      diagnostic assay for the detection of this mutation and to evaluate its frequency
      in a sample of AMD patients. METHODS: A primer probe set was designed from exon
      104 of the HEMICENTIN-1 gene to differentiate between mutant and wild type
      alleles. A region spanning the mutation was amplified by PCR using a LightCycler
      (Roche Diagnostic). The mutation was then detected by melt curve analysis of the
      hybrid formed between the PCR product and a specific fluorescent probe. The
      frequency of the mutation within the Northern Ireland population was evaluated by
      assaying 508 affected AMD patients, 25 possibly affected and 163 controls.
      RESULTS: This assay clearly discriminates between the A16,263G mutant and wild
      type HEMICENTIN-1 alleles. The wild type sequence has a single base mismatch with
      the probe which decreases the stability of the hybrid, resulting in a lower TM
      (TM=51.27 degrees C) than that observed for the perfectly matched mutant allele
      (TM=59.9 degrees C). The mutant allele was detected in only one of the 696
      subjects, an affected AMD patient. CONCLUSIONS: We describe a rapid assay for the
      genotyping of the Gln5345Arg mutation using real-time fluorescence PCR to
      facilitate rapid processing of samples through combined amplification and
      detection steps. These characteristics are suitable for a clinical setting where
      high throughput diagnostic procedures are required. The frequency of this
      mutation within the Northern Ireland population has been estimated at 0.2%,
      concurring with previous findings that this mutation is a rare variant associated
      with AMD. A rapid diagnostic assay will facilitate a reliable and convenient
      evaluation of the frequency of the Gln5345Arg mutation and its association with
      AMD within other populations.

PMID- 15467526
TI  - The Randomized Nitric Oxide Tocolysis Trial (RNOTT) for the treatment of preterm
      labor.
AB  - OBJECTIVE: This study was undertaken to assess the effectiveness of glyceryl
      trinitrate (GTN) patches in comparison with beta2 sympathomimetics (beta2) for
      the treatment of preterm labor. STUDY DESIGN: A multicenter, multinational,
      randomized controlled trial was conducted in tertiary referral teaching
      hospitals. Women in threatened preterm labor with positive fetal fibronectin or
      ruptured membranes between 24 and 35 weeks' gestation were recruited and randomly
      assigned to either beta2 or GTN with rescue beta2 tocolysis if moderate-to-strong
      contractions persisted at 2 hours. Obstetric and neonatal outcomes were assessed.
      RESULTS: Two hundred thirty-eight women were recruited and randomly assigned, 117
      to beta2 and 121 to GTN. On a strict intention-to-treat basis, there was no
      significant difference in the time to delivery using Kaplan-Meier curves (P =
      .451). At 2 hours, 27% of women receiving beta2 had moderate or stronger
      contractions compared with 53% in the GTN group (P < .001). This led to 35% of
      women in the GTN group receiving rescue treatment. If delivery or requirement for
      beta2 rescue are regarded as treatment failure, then a significant difference was
      observed between the 2 arms (P = .0032). There were no significant differences in
      neonatal outcomes. CONCLUSION: GTN is a less efficacious tocolytic compared with
      ss2 sympathomimetics.

PMID- 15467527
TI  - Racial and ethnic disparities in preterm birth: the role of stressful life
      events.
AB  - OBJECTIVE: The purpose of this study was to examine racial-ethnic disparities in
      stressful life events before and during pregnancy and to assess the relationship
      between stressful life events and racial-ethnic disparities in preterm birth.
      STUDY DESIGN: Using data from the Pregnancy Risk Assessment Monitoring System, we
      conducted a retrospective cohort analysis of a sample of 33,542 women from 19
      states who were delivered of a live-born infant in 2000. Principal component
      analysis was used to group 13 stressful life events into 4 stress constructs:
      emotional, financial, partner-related, and traumatic. Racial-ethnic disparities
      in stressful life events were assessed with the use of bivariate and multivariate
      regression analyses. The contribution of stressful life events to racial-ethnic
      disparities in preterm birth was evaluated with the use of stepwise regression
      model and interaction terms. RESULTS: Black women and American Indian/Alaska
      Native women reported the highest number of stressful life events in the 12
      months before delivery. Compared with non-Hispanic white women, black women were
      24% more likely to report emotional stressors, 35% more likely to report
      financial stressors, 163% more likely to report partner-related stressors, and
      83% more likely to report traumatic stressors. The addition of stress constructs
      to the stepwise regression model minimally affected the association between race
      ethnicity and preterm birth, and none of the stress constructs were significantly
      associated with preterm birth. There were no significant interaction effects
      between race-ethnicity and stress on preterm birth, except for a modest effect
      between black race and traumatic stressors. CONCLUSION: There are significant
      racial-ethnic disparities in the experience of stressful life events before and
      during pregnancy. Stressful life events do not appear to contribute significantly
      to racial-ethnic disparities in preterm birth.

PMID- 15467528
TI  - Twins and triplets: the effect of plurality and growth on neonatal outcome
      compared with singleton infants.
AB  - OBJECTIVE: Information on outcome by gestational age from large numbers of twins
      and triplets is limited and is important for counseling and decision-making in
      obstetric practice. We reviewed one of the largest available neonatal databases
      to describe mortality and morbidity rates and growth in newborn infants from
      multiple gestations and compared these data with data for singletons. STUDY
      DESIGN: Data from a large prospectively recorded neonatal database that
      incorporated neonatal records from January 1997 to July 2002 were reviewed. We
      evaluated birth weight and neonatal mortality and morbidity rates that affected
      long-term outcome for each week of gestational age from 23 to 35 weeks of
      gestation for all nonanomolous inborn twins and triplets who were admitted to the
      neonatal intensive care unit and compared these data to all singletons who met
      similar criteria during the same time period. RESULTS: There were 12,302 twin and
      2155 triplet births that met the entry criteria. The data for these newborn
      infants were compared with 36,931 singletons. Average birth weights at each
      gestational week were similar for all gestational ages until 29 weeks of
      gestation for triplets and 32 weeks of gestation for twins. After these
      gestational ages, the entire difference between twins and singletons was due to
      the weight of the smaller twin; the larger twins' mean weights were similar to
      singletons at all weeks that were studied. Birth order at each week also did not
      affect neonatal mortality rates, even when corrected for route of delivery and
      antenatal steroids. Neonatal morbidities associated with adverse long-term
      outcomes (intraventricular hemorrhage, retinopathy of prematurity, necrotizing
      enterocolitis) were also not different between multiple infants and singletons.
      Intrauterine growth restriction (IUGR) was associated with increased mortality
      rates at all gestational ages, but in the absences of IUGR, discordance was not.
      CONCLUSION: Data on a large number of twins and triplets provide reassurance that
      neonatal outcome at all viable premature weeks of gestation are similar to
      singletons. Intrauterine growth restriction and prematurity are therefore the
      principal issues that drive neonatal mortality and morbidity rates in multiple
      gestations. These data are important for obstetric decision-making and patient
      counseling.

PMID- 15467529
TI  - Dads as breastfeeding advocates: results from a randomized controlled trial of an
      educational intervention.
AB  - OBJECTIVE: Recognizing that an expectant father may influence a mother's decision
      to breast- or formula-feed, we tested the effectiveness of a simple, educational
      intervention that was designed to encourage fathers to advocate for breastfeeding
      and to assist his partner if she chooses to breastfeed. STUDY DESIGN: We
      conducted a randomized controlled trial in which expectant fathers (n = 59) were
      assigned randomly to attend either a 2-hour intervention class on infant care and
      breastfeeding promotion (intervention) or a class on infant care only (control
      group). The classes, which were led by a peer-educator, were interactive and
      informal and utilized different media to create an accessible environment for
      participants. Couples were recruited during the second trimester from a
      university obstetrics practice. RESULTS: Overall, breastfeeding was initiated by
      74% of women whose partners attended the intervention class, as compared with 41%
      of women whose partners attended the control class (P = .02). CONCLUSION:
      Expectant fathers can be influential advocates for breastfeeding, playing a
      critical role in encouraging a woman to breastfeed her newborn infant.

PMID- 15467530
TI  - A practical approach to the diagnosis of polycystic ovary syndrome.
AB  - The diagnosis of polycystic ovary syndrome (PCOS) is primarily achieved through
      clinical history and physical findings. The principle features are hirsutism or
      biochemical evidence of excess androgen production and irregular menstrual
      bleeding caused by the chronic anovulation. Associated findings include insulin
      resistance with compensatory hyperinsulinemia and obesity. Ultrasound imaging of
      the ovary has facilitated the diagnosis. It is important to exclude conditions
      that may mimic PCOS, such as hyperthecosis, congenital adrenal hyperplasia, 21
      hydroxylase deficiency, Cushing's syndrome, and androgen-producing neoplasms.
      These disorders are usually revealed by appropriate laboratory assessment.
      Screening tests include measurement of serum total testosterone, DHEA sulfate,
      and 17-hydroxyprogesterone. In addition, in the obese individual, determinations
      of glucose and insulin levels, as well as a lipid profile, are highly
      recommended.

PMID- 15467531
TI  - Intraperitoneal serous adenocarcinoma: a critical appraisal of three hypotheses
      on its cause.
AB  - OBJECTIVE: Serous ovarian, Fallopian tube, and peritoneal adenocarcinomas are
      remarkably similar, both in their morphology, as well as in their clinical
      behavior. Despite extensive clinical and fundamental research, controversy still
      exists on the origin of serous female adnexal tumors. Difficulties in
      identification of site of origin at late stage the of disease at detection, when
      ovary, Fallopian tube, and the abdominal cavity are usually all involved, in
      addition to their macroscopic and microscopic resemblance, are major causes of
      this debate. In 3 hypotheses, 3 possible tissues of origin are proposed: the
      ovarian surface epithelium, the Fallopian tube epithelium, and the secondary
      Mullerian system. STUDY DESIGN: We searched for all peer-reviewed articles and
      reviews that examined "serous ovarian carcinoma," "Fallopian tube carcinoma,"
      "Mullerian system," "ovarian surface epithelium," "tubal epithelium," and
      "peritoneal." We included only articles that could give information on the origin
      of serous carcinomas. Additional articles were added by examining references of
      overview articles in relevant fields. RESULTS: Discussed are the experimental
      data underlying these hypotheses. CONCLUSION: An attempt is made to integrate the
      3 hypotheses into a comprehensive model of serous intraperitoneal
      adenocarcinogenesis. It can be concluded that the Fallopian tubes play a major
      role in the development of female serous cancer.

PMID- 15467532
TI  - Oral contraceptive use, reproductive history, and risk of epithelial ovarian
      cancer in women with and without endometriosis.
AB  - OBJECTIVE: Women with endometriosis may be at an increased risk of ovarian
      cancer. It is not known whether reproductive factors that reduce the risk of
      ovarian cancer in general also reduce risk in women with endometriosis. We
      investigated whether the odds ratios for ovarian cancer that were associated with
      oral contraceptive use, childbearing, hysterectomy, and tubal ligation differ
      among women with and without endometriosis. STUDY DESIGN: We pooled information
      on the self-reported history of endometriosis from 4 population-based case
      controlled studies of incident epithelial ovarian cancer, comprising 2098 cases
      and 2953 control subjects. We obtained data on oral contraceptive use,
      childbearing, breastfeeding, gynecologic surgical procedures, and other
      reproductive factors on each woman. Multivariable unconditional logistic
      regression was used to calculate odds ratios and 95% CI for ovarian cancer among
      women with endometriosis compared with women without endometriosis. Similar
      methods were used to assess the frequencies of risk factors among women with and
      without endometriosis. Adjustments were made for age, parity, oral contraceptive
      use, tubal ligation, family history of ovarian cancer, and study site. RESULTS:
      Women with endometriosis were at an increased risk of ovarian cancer (odds ratio,
      1.32; 95% CI, 1.06-1.65). Using oral contraceptives, bearing children, and having
      a tubal ligation or hysterectomy were associated with a similar reduction in the
      odds ratios for ovarian cancer among women with and without endometriosis. In
      particular, the use of oral contraceptives for >10 years was associated with a
      substantial reduction in risk among women with endometriosis (odds ratio, 0.21;
      95% CI, 0.08-0.58). CONCLUSION: Women with endometriosis are at an increased risk
      of epithelial ovarian cancer. Long-term oral contraceptive use may provide
      substantial protection against the disease in this high-risk population.

PMID- 15467533
TI  - Spontaneous embryonic loss following in vitro fertilization: incidence and effect
      on outcomes.
AB  - OBJECTIVES: The purpose of this study was to determine the early spontaneous loss
      rate in multiple pregnancies following assisted reproductive technology (ART).
      STUDY DESIGN: Analysis of pregnancies following ART as related to the initial
      number of embryos and maternal age was performed. RESULTS: At least one
      spontaneous loss was observed in 47.0% (95% CI 29.8-64.9) of quadruplets, 59.3%
      (95% CI 48.2-69.8) of triplets, and 35.2% (95% CI 29.6-41.2) of twins. The
      increased loss rates in mothers > or =35 years was related to early twin
      pregnancies, but not to early triplet and quadruplet gestations. We could not
      find an effect of the starting number of embryos on either gestational age or
      birth weight characteristics. CONCLUSION: Our observations did not identify a
      clear relation between early spontaneous loss of multiple gestations and either
      initial number of embryos or maternal age. Other factors might be involved in the
      outcome of ART multiple pregnancies.

PMID- 15467534
TI  - Are racial differences in vaginal pH explained by vaginal flora?
AB  - OBJECTIVES: The study assessed racial differences in vaginal pH among women
      without bacterial vaginosis. STUDY DESIGN: Data from the Vaginal Infections and
      Prematurity (VIP) Study were analyzed. From 1984 to 1989, 13,917 largely low
      income women were enrolled during routine prenatal visits from 23 to 26 weeks'
      gestation. Vaginal cultures, Gram stains, and pH levels were collected.
      Comparisons of pH by race were made among women with Gram stain scores <7 and
      without trichomoniasis before and after adjustment for actual Gram stain score.
      RESULTS: Among women with Gram stain scores <7, there was a modest but
      statistically significant racial difference in vaginal pH level. However, after
      controlling for difference in Gram stain score, age, and study site, there was no
      longer a significant difference in vaginal pH. CONCLUSION: There is no
      significant difference in vaginal pH level between black and white women after
      controlling for differences in confounding factors, particularly vaginal flora.

PMID- 15467535
TI  - Sexual function among women with urinary incontinence and pelvic organ prolapse.
AB  - OBJECTIVE: The objective of this research was to determine whether sexual
      complaints, such as dyspareunia, are associated with pelvic floor disorders.
      STUDY DESIGN: We used data collected for the Maryland Women's Health Study. Among
      adult women scheduled for hysterectomy, we used multiple logistic regression
      analysis to identify characteristics associated with 4 sexual complaints:
      decreased libido, vaginal dryness, dyspareunia, and anorgasmia. RESULTS: Among
      1299 participants, 495 (38.1%) had evidence of pelvic floor disorders. Sexual
      complaints were significantly more common among women with pelvic floor disorders
      (53.2% vs 40.4%, P < .01). In the multiple regression model, urinary incontinence
      was significantly associated with low libido (odds ratio [OR] 1.96), vaginal
      dryness (OR 2.11), and dyspareunia (OR 2.04), independent of age, educational
      attainment, and race. In contrast, pelvic organ prolapse was not associated with
      any sexual complaint. CONCLUSION: In a cohort of women planning hysterectomy,
      women with urinary incontinence were significantly more likely to report sexual
      complaints.

PMID- 15467536
TI  - The borderline or weakly positive Hybrid Capture II HPV test: a statistical and
      comparative (PCR) analysis.
AB  - OBJECTIVES: Recent studies have hypothesized that laboratory contamination may
      influence interpretation of Hybrid Capture II (HCII) human papillomavirus (HPV)
      detection assay values. STUDY DESIGN: To test this hypothesis, 572 consecutive
      HCII samples were statistically evaluated to test the null hypothesis that cross
      well contamination was not present. In addition, 874 consecutive paired samples
      from patients followed by both HCII and polymerase chain reaction (PCR) analysis
      were compared. RESULTS: A Kendall's tau measure of association among adjacent
      wells yielded a P value of .016, rejecting the null hypothesis of no
      contamination. Analysis of relative light unit values between 0.8 and 1.5
      rejected the null hypothesis at P=.077. Moreover, PCR positivity was
      significantly higher for samples with HCII values above 1.5 vs 0.8 to 1.5
      (P=.001). CONCLUSION: Cross-well contamination of samples occurs during
      processing, and may influence interpretation of some borderline positives. The
      proportion of cases at risk is low (<3%). Nevertheless, this information may be
      germane to the interpretation and reporting of marginally positive HCII test
      values.

PMID- 15467537
TI  - Altered distribution of mannose-binding lectin alleles at exon I codon 54 in
      women with vulvar vestibulitis syndrome.
AB  - OBJECTIVES: Mannose-binding lectin (MBL) is active in the innate immune defense
      against microorganisms. In this study, we determined whether vulvar vestibulitis
      syndrome, a disorder of unknown etiology, was associated with an altered
      distribution of MBL alleles. STUDY DESIGN: Buccal swabs were obtained from women
      with vulvar vestibulitis syndrome in New York (62) and from 2 cities in Sweden
      (60), as well as control women in New York (48) and Sweden (51). DNA was tested
      for a single nucleotide polymorphism at codon 54 in exon I by polymerase chain
      reaction, endonuclease digestion, and gel electrophoresis. Blood samples were
      also obtained from the New York women and tested by ELISA for plasma MBL
      concentrations. The relationships between genotype, allele frequencies, blood MBL
      levels, and diagnosis were analyzed by Fisher exact test and one-way analysis of
      variance. RESULTS: The variant MBL allele, MBL*B, was detected in 35.5% and 26.7%
      of vulvar vestibulitis patients from New York and Sweden, respectively. Only
      12.5% of New York controls (P=.007) and 9.8% of Swedish controls (P=.01) were
      MBL*2-positive. All women, with one exception, who were positive for MBL*B were
      MBL*A/MBL*B heterozygotes. Women who carried MBL*B had almost a 10-fold reduction
      in median plasma MBL concentrations (278 ng/mL), as opposed to women who were
      MBL*A homozygotes (1980 ng/mL) (P < .0001). CONCLUSION: MBL*B carriage and
      reduced plasma MBL levels are more common in women with vulvar vestibulitis
      syndrome than in control patients, and may contribute to symptomatology in a
      subset of patients.

PMID- 15467538
TI  - Expression of HOXA11 gene in human endometrium.
AB  - OBJECTIVE: This study was conducted to examine HOXA11 gene expression in the
      human endometrium during normal menstrual cycle. STUDY DESIGN: Expression of
      HOXA11 was examined in the endometrium by in situ hybridization and
      semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR).
      RESULTS: In the proliferative and early secretory endometrium, both glandular and
      stromal cells expressed HOXA11 after hybridization. It is interesting to note
      that the expression in glandular epithelium was dramatically decreased or
      disappeared in the midsecretory phase at the time of implantation. This
      expression patterning was kept in the late secretory endometrium and decidua of
      early pregnancy, whereas in stromal cells, a high-level expression was found and
      no variations were detected during the menstrual cycle. Semiquantitative RT-PCR
      analysis demonstrated that total HOXA11 messenger RNA levels were markedly
      increased in the midsecreatory endometrium. CONCLUSION: This study reveals a
      novel expression pattern for HOXA11 gene in human endometrium and the
      downregulation of HOXA11 in glandular epithelium may be necessary for the
      differentiation and receptivity of endometrium.

PMID- 15467539
TI  - Neonatal morbidity in second twin according to gestational age at birth and mode
      of delivery.
AB  - OBJECTIVE: This study was undertaken to assess the risk of neonatal morbidity in
      the second twins. STUDY DESIGN: We carried out a cohort study of 128,219 live
      born second twins in the United States, 1995 through 1997. The study subjects
      were divided into 3 groups: second twins delivered by cesarean section after
      vaginal delivery of the first twin (V-C), both twins delivered vaginally (V-V),
      and both twins delivered by cesarean section (C-C). RESULTS: The rates of low 5
      minute Apgar score, mechanical ventilation, and seizure were higher in the V-C
      group (8.27%, 13.39%, and 0.31%) than in the V-V (3.07%, 7.51%, and 0.08%) and
      the C-C (2.66%, 8.53%, and 0.06%) groups. The V-C associated increase in risk
      remained after adjustment for confounding factors and was more evident at term
      than preterm. CONCLUSION: The risk of neonatal morbidity is increased in second
      twins who had a cesarean section after vaginal delivery of the first twin,
      especially at term.

PMID- 15467540
TI  - Neonatal mortality in second twin according to cause of death, gestational age,
      and mode of delivery.
AB  - OBJECTIVE: The purpose of this study was to assess the risk of neonatal death in
      the second twin. STUDY DESIGN: We carried out a retrospective cohort study of
      128,219 live born second twins in the United States for the years 1995 through
      1997. The study subjects were divided into 3 groups: second twins who were
      delivered by cesarean delivery after vaginal delivery of the first twin (group
      1), both twins delivered vaginally (group 2), and both twins delivered by
      cesarean delivery (group 3). RESULTS: The risk of asphyxia-related neonatal
      deaths was increased in groups 1 and 2; the increased risk in group 1 was
      stronger in term births than in preterm births. CONCLUSION: The risk of neonatal
      deaths, especially for term infants with asphyxia-related deaths, is increased
      for the second twins who are delivered by cesarean delivery after vaginal
      delivery of the first twins.

PMID- 15467541
TI  - Interleukin-6, but not relaxin, predicts outcome of rescue cerclage in women with
      cervical incompetence.
AB  - OBJECTIVE: We investigated the potential roles of relaxin and subclinical intra
      amniotic inflammation by quantitating amniotic fluid relaxin and interleukin-6
      concentrations for the prediction of outcome of rescue cerclage in women with
      cervical incompetence. STUDY DESIGN: Cervical incompetence was diagnosed when
      cervical dilatation exceeded 2 cm with intact but bulging membranes and no
      detectable uterine activity. Each woman underwent amniocentesis to facilitate the
      performance of a rescue cerclage between 15 and 27 weeks of gestation (n=40
      women). Forty-five additional women who underwent amniocentesis for chromosomal
      testing between 16 and 27 weeks of gestation served as a control group. All
      control patients were delivered of chromosomally normal infants at>37 weeks of
      gestation. All cases and control patients were singleton gestations. Interleukin
      6 and relaxin were determined in all amniotic fluid samples by enzyme-linked
      immunosorbent assay. RESULTS: Amniotic fluid interleukin-6 levels were
      significantly higher in women with cervical incompetence than in control patients
      (control patients, 50.4 pg/mL [range, 19.4-97.4 pg/mL] vs cervical incompetence
      patients, 5459.1 pg/mL [range, 1131.4-14425.7 pg/mL] ; P < .001). In contrast to
      interleukin-6, relaxin levels did not differ between the 2 groups (control
      patients, 67.5 pg/mL [range, 35.1-153.5 pg/mL] vs cervical incompetence patients,
      45.6 pg/mL [range, 30.1-75.5 pg/mL]; P=.061). There was a significant difference
      in interleukin-6 levels in women with shorter latencies (P < .01 for all latency
      intervals that were examined: delivery within 24 hours, 3 days, 7 days, before 33
      and 37 completed weeks of gestation). Linear regression analysis with the use of
      the latency interval from cerclage to delivery as the dependent and with
      interleukin-6 as the independent variable revealed a significant inverse
      relationship (r=-0.62; P < .001 after log transformation of interleukin-6). There
      was no relationship on regression analysis between relaxin and the latency
      interval. CONCLUSION: Amniotic fluid interleukin-6 is increased in patients with
      cervical incompetence, which suggests that subclinical inflammation may
      contribute to cervical incompetence. Further, an elevated interleukin-6 level
      predicts a cerclage short-latency interval between cerclage and delivery. In
      contrast with interleukin-6, amniotic fluid relaxin does not appear to contribute
      to cervical incompetence-induced cervical dilation.

PMID- 15467543
TI  - The immediate management of fresh obstetric fistulas.
AB  - OBJECTIVE: It has been a general rule to wait with the repair of an obstetric
      fistula for a minimum period of 3 months allowing the patient to become an
      outcast. In a prospective way an immediate management was studied and antibiotics
      were not used, all according to basic surgical principles. METHODS: A total of
      1716 patients with a fistula duration of 3 to 75 days after delivery were treated
      immediately on presentation by catheter and/or early closure. Instead of
      antibiotics, a high oral fluid regimen was instituted. The fistulas were
      classified according to anatomic and physiologic location in types I, IIAa, IIAb,
      IIBa, and IIBb, and according to size in small, medium, large, and extensive. The
      operation became progressively more complicated from type I through type IIBb and
      from small through extensive. RESULTS: At first attempt 1633 fistulas (95.2%)
      were closed and another 57 could be closed at further attempt(s), accounting for
      a final closure in 1690 patients (98.5%); 264 patients (15.4%) were healed by
      catheter only. Of these 1690 patients with a closed fistula, 1575 (93.2%) were
      continent and 115 (6.8%) were incontinent. The results as to closure and to
      continence became progressively worse from type I through type IIBb and from
      small through extensive. Postoperative wound infection was not noted;
      postoperative mortality was encountered in 6 patients (0.4%). CONCLUSION: This
      immediate management proves highly effective in terms of closure and continence
      and will prevent the patient from becoming an outcast with progressive
      downgrading medically, socially, and mentally.

PMID- 15467542
TI  - Periconceptional folic acid/multivitamin supplementation and twin pregnancy.
AB  - OBJECTIVE: Results of our previous randomized controlled trial suggested an
      increase of twin pregnancies that was associated with the use of a multivitamin
      that contained folic acid during the periconceptional period. These findings were
      confirmed by US and Swedish studies, but not in the Chinese population. The aim
      of this analysis is to evaluate this possible association in a population-based
      data set. STUDY DESIGN: The population-based large control data set of the
      Hungarian Case-Control Surveillance of Congenital Abnormalities (1980-1996) was
      evaluated. Control pregnant women were differentiated according to pre- and
      postconceptional supplementation of folic acid (in general 6 mg), multivitamins
      that contained 0.1 to 1.0 mg folic acid, folic acid plus multivitamin, and the
      prevalence of twin pregnancies was compared with the prevalence of twin
      pregnancies in the women who did not received supplements as referent. RESULTS:
      Of 38,151 women, 395 women gave birth to twins. The prevalence of twin births was
      0.78% in the unsupplemented group; the rate of twin pregnancies was 1.52% after
      the preconceptional supplementation (adjusted odds ratio, 1.80; 95% CI, 1.14
      2.85). The proportions of twin pregnancies were 1.14%, 1.45%, and 2.00% after the
      postconceptional folic acid, multivitamin, and folic acid plus multivitamin
      supplementation, respectively. CONCLUSION: Our findings suggest that both pre-
      and postconceptional supplementation of a high dose of folic acid and
      multivitamins are associated with a slight increase of the incidence of twin
      pregnancies.

PMID- 15467544
TI  - Rising cesarean rates: are patients sicker?
AB  - OBJECTIVE: Our study explored if patient risk factors for cesarean delivery (CD)
      are changing over time. STUDY DESIGN: North Carolina birth certificates from 1995
      were used to build a logistic regression model to predict the probability of
      primary CD. The model estimated each patient's probability of primary CD for 4
      years of deliveries (397,793). The percentage of the population in each of the 10
      CD risk deciles were compared across years. RESULTS: The incidence of primary CD
      rose from 16.6 to 18.4 (P<.0001). Despite this increase over time, more women
      were low risk (probability of CD <10%) (43.2% to 46.4%, P<.0001). The cesarean
      rate even rose for women in the lowest risk group (4.6% to 5.9%, P<.0001).
      CONCLUSION: The rate of primary CD is increasing, despite improvements in patient
      risk profile. The increasing CD rate may result from changes in physician
      behavior, institutional factors, and increasing patient demand for elective
      cesarean delivery.

PMID- 15467545
TI  - Evaluation of body composition of large-for-gestational-age infants of women with
      gestational diabetes mellitus compared with women with normal glucose tolerance
      levels.
AB  - OBJECTIVE: The purpose of this study was to determine whether there is a
      difference in body composition and the factors that are associated with fat mass
      in the large-for-gestational-age infants of women with gestational diabetes
      mellitus compared with the large-for-gestational-age infants of women with normal
      glucose tolerance levels. STUDY DESIGN: Large for gestational age was defined as
      weight >90th percentile for gestational age, race, and sex on the basis of our
      population's normative data. Anthropometric measurements and/or total body
      electrical conductivity estimated body composition that included fat mass,
      percent body fat, and lean body mass were obtained. Multiple stepwise regression
      was used to determine factors correlating with fat mass. RESULTS: Fifty cases of
      women with gestational diabetes mellitus and 52 cases of women with normal
      glucose tolerance levels were evaluated. Infants of mothers with gestational
      diabetes mellitus had increased fat mass (662 vs 563 g; P = .02) and percent body
      fat (16.2% vs 13.5%; P = .002) but decreased lean body mass (3400 vs 3557 g; P =
      .0009), as compared with infants of mothers with normal glucose tolerance levels,
      despite similar birth weights. Stepwise regression on all 102 women showed
      gestational age and a diagnosis of gestational diabetes mellitus correlated with
      fat mass (r2 = 0.11; P = .001). For gestational diabetes mellitus alone, both
      gestational age and fasting value of the oral glucose tolerance test correlated
      with fat mass and percent body fat (r2 = 0.33 [P = .0009] and r2 = 0.26 [P =
      .005], respectively). CONCLUSION: Large-for-gestational-age infants of mothers
      with gestational diabetes mellitus have increased fat mass and decreased lean
      body mass compared with infants of mothers with normal glucose tolerance levels.
      In gestational diabetes mellitus, gestational age and fasting value of the oral
      glucose tolerance test correlated best with fat mass.

PMID- 15467546
TI  - Birth weight references for triplets.
AB  - OBJECTIVE: The purpose of this study was to formulate growth references that
      reflect triplet fetal and neonatal populations at each gestational age by
      combining serial ultrasonographic estimates of fetal weights and measured birth
      weights. STUDY DESIGN: This historical cohort study was based on 188 pregnancies
      of live-born triplets of > or =23 weeks' gestation. Ultrasonographic fetal weight
      measures were modeled as a function of gestational age for each infant. Linear
      regression models were used to fit the data, and weight percentiles were
      generated. RESULTS: Well-grown triplets fell substantially below singletons by 30
      weeks and twins after 34 weeks. Trichorionic vs monochorionic or dichorionic
      placentation resulted in 27% higher growth at the 10th %ile, 5% higher growth at
      the 50th %ile, and 4% higher growth at the 90th %ile by 34 weeks. CONCLUSION: The
      overall pattern of fetal growth for well-grown triplets does not differ from that
      of singletons and twins until late gestation, confirming that, in utero, well
      grown children have similar growth potentials, regardless of plurality.

PMID- 15467547
TI  - The immunologic profile of infants born after maternal immunoglobulin treatment
      and intrauterine platelet transfusions for fetal/neonatal alloimmune
      thrombocytopenia.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether maternally
      administered intravenous immunoglobulins (IVIG) and intrauterine platelet
      transfusions (IUPT) for fetal/neonatal alloimmune thrombocytopenia (FNAIT) affect
      the development of the fetal immune system. STUDY DESIGN: The lymphocyte subset
      distribution of mononuclear cells of cord blood of 20 FNAIT newborns was analyzed
      by flow cytometry and compared with a control group of healthy newborns and a
      reference group treated with intrauterine erythrocyte transfusions (IUET) for
      hemolytic disease. RESULTS: The percentage of monocytes, natural killer (NK)
      cells, ratios of mature and immature T cells and B cells, and resting or
      activated cells were not significantly different compared to the control group.
      In addition, the B-cell and T-cell populations showed a normal in vitro antibody
      production and T-cell proliferation when compared with the control group.
      CONCLUSION: Antenatal treatment for FNAIT with maternal IVIG with or without IUPT
      is not associated with lymphocyte activation or premature maturation of the
      neonatal immune system.

PMID- 15467548
TI  - Angiotensin-converting enzyme gene polymorphism in preeclampsia and normal
      pregnancy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the angiotensin-converting
      enzyme gene polymorphism in pregnant women with and without preeclampsia. STUDY
      DESIGN: Preeclampsia was defined as hypertension and pathologic proteinuria in
      pregnant women after gestational week 20. Genomic DNA was isolated from
      leukocytes. The insertion-deletion polymorphism in intron 16 of the angiotensin
      converting enzyme gene was detected in DNA samples with the use of the polymerase
      chain reaction. Chi-squared and Student t tests were used for statistical
      analysis. RESULTS: In preeclampsia (n=51 women) angiotensin-converting enzyme
      genotypes were deletion-D (DD) in 16 women (31%), insertion-I (II) in 12 women
      (24%), and insertion-deletion in 23 women (45%); in the control group (n=71), the
      angiotensin-converting enzyme genotypes were DD in 21 women (30%), II in 17 women
      (24%), and insertion-deletion in 33 women (46%). Angiotensin-converting enzyme
      genotype distribution and allelic frequencies were not different between groups.
      CONCLUSION: No difference in the angiotensin-converting enzyme genotype
      distribution was found between preeclampsia and normal pregnancy. The results
      showed no association between angiotensin-converting enzyme polymorphism and the
      development of preeclampsia.

PMID- 15467549
TI  - Estimates of risk of venous thrombosis during pregnancy and puerperium are not
      influenced by diagnostic suspicion and referral basis.
AB  - OBJECTIVES: The purpose of this study was to determine the relative risk of deep
      vein thrombosis (DVT) during pregnancy and puerperium in a setting that was not
      influenced by diagnostic suspicion and referral bias. STUDY DESIGN: Three hundred
      ninety-three consecutive females with suspicion of a first episode of venous
      thrombosis were referred in the same way to diagnostic centers. Medical history
      was obtained before objective testing for deep vein thrombosis. RESULTS: Seventy
      six of the 393 females were diagnosed as having deep vein thrombosis; the others
      were used as control subjects. The odds ratios for pregnancy, cesarean section,
      and puerperium after adjustment for age, center, family history, and calendar
      time were, respectively, 5.7 (95% CI 2.5-12.9), 4.0 (95% CI 1.3-12.6), and 2.9
      (95% CI 1.2-6.9). CONCLUSION: In this case-control study, in which patients and
      control patients were subject to the same referral and diagnostic procedures, we
      found similar risk estimates for pregnancy and puerperium as in previous studies.
      Our findings show that previous studies were less affected by diagnostic
      suspicion and referral bias than presumed.

PMID- 15467550
TI  - Effect of tracheal occlusion on peripheric pulmonary vessel muscularization in a
      fetal rabbit model for congenital diaphragmatic hernia.
AB  - OBJECTIVE: This study was undertaken to evaluate the effects on peripheric
      pulmonary vessel muscularization by tracheal occlusion (TO) performed at
      different gestational ages in fetal rabbits with surgically induced diaphragmatic
      hernia. STUDY DESIGN: In 23 New Zealand white does, both ovarian end fetuses
      underwent surgical creation of diaphragmatic hernia at 23 days of gestation
      (pseudoglandular phase). At 26, 27, or 28 days 1 fetus underwent TO, the
      contralateral one underwent a sham operation for a total of 46 fetuses. At 30
      days (alveolar phase), fetuses were harvested together with 1 nonoperated
      internal control. Lungs were processed for vascular morphometry. Proportionate
      medial thickness and muscularization of intra-acinar vessels were evaluated.
      RESULTS: Late TO (day 28; saccular phase) normalizes the lung-to-body weight
      ratio and causes significant medial thinning in vessels up to 35 microm diameter.
      CONCLUSION: Tracheal occlusion decreases muscularization of intra-acinar
      pulmonary vessels in a gestational age-dependent fashion, with maximal effect
      when TO is performed at 28 days.

PMID- 15467551
TI  - Regulation of amniotic fluid volume: intramembranous solute and volume fluxes in
      late gestation fetal sheep.
AB  - OBJECTIVE: Recent studies suggest that amniotic fluid volume is regulated by the
      rate of intramembranous absorption of amniotic fluid into fetal blood. The
      purpose of the present study was to determine the simultaneous intramembranous
      solute and water fluxes to gain insight into the intramembranous transport and
      amniotic fluid volume regulatory mechanisms. STUDY DESIGN: All major amniotic
      inflows and outflows, except intramembranous flow, were eliminated in 10 fetal
      sheep over 8 hours by occlusion of the fetal trachea and esophagus; the fetal
      urine was drained to the exterior. Amniotic fluid composition and volume were
      measured before and at the end of the 8 hours. Solute and volume fluxes through
      the intramembranous pathway were calculated from amniotic fluid concentration and
      volume changes. Statistical analyses included t-tests, linear regression, and
      analyses of variance. RESULTS: Amniotic fluid volume decreased by 128 +/- 24 (SE)
      mL over 8 hours (P < .001), which was correlated only marginally with the fetal
      to amniotic fluid osmotic gradient (r=0.59; P = .072). Amniotic fluid sodium,
      chloride, calcium, and bicarbonate concentrations increased (P < .0001), even
      though there were net outward fluxes of these solutes; these outward fluxes
      occurred against concentration gradients; and the clearances of these solutes
      were the same despite widely differing amniotic fluid concentrations and fetal
      blood to amniotic fluid concentration gradients. With the use of multivariate
      regression, intramembranous solute fluxes separated into 2 components, which were
      a primary outward flux that correlated with the volume flux and a minor inward
      component that correlated with the fetal plasma to amniotic fluid concentration
      gradient for sodium, chloride, calcium (P < .001), and bicarbonate (P < .02). The
      concentration-dependent fluxes averaged approximately one third of the bulk
      fluxes and were in the opposite direction. CONCLUSION: The poor correlation of
      amniotic fluid volume reduction with the fetal-to-amniotic fluid osmotic gradient
      shows that the primary mechanism that mediates intramembranous volume flow is not
      passive osmosis in the normal fetus under basal conditions. The strong
      correlations of solute fluxes simultaneously with volume flux and concentration
      gradients suggest that intramembranous solute fluxes are mediated by both bulk
      flow and passive diffusion. The small size of the passive component relative to
      the size of the bulk component suggests that intramembranous solute transfer is
      mediated primarily by bulk flow with a smaller and usually oppositely directed
      contribution by diffusion down concentration gradients. Bulk flow by vesicular
      transport is the only known physiologic transport mechanism that is compatible
      with these data, but it is not known whether this occurs in the amnion or
      intramembranous blood vessels or both.

PMID- 15467552
TI  - Cardiovascular and renal disease in the adolescent guinea pig after chronic
      placental insufficiency.
AB  - OBJECTIVE: The aim of this study was to determine the long-term effects of
      chronic placental insufficiency on the metabolic state and organ structure in the
      fetal and adolescent guinea pig. STUDY DESIGN: The maternal uterine artery was
      ligated at day 28-30 to reduce placental function and restrict fetal growth.
      Whole body and tissue weights and plasma metabolites were determined at 60 days
      of gestation and 8 weeks of age; tissue structure was determined at the latter
      age in restricted and control offspring. RESULTS: Fetal growth restriction
      increased fibrosis in the heart and kidneys (P < .05), increased aortic wall
      thickening (P < .01), reduced the number of glomeruli in the kidneys (P < .05),
      and increased the plasma urea and chloride in adolescent offspring. CONCLUSION:
      This study demonstrates that diseases in the heart, aorta, and kidneys that
      result from an adverse prenatal environment are evident at adolescence and may
      contribute to subsequent adult disease.

PMID- 15467553
TI  - Levator ani thickness variations in symptomatic and asymptomatic women using
      magnetic resonance-based 3-dimensional color mapping.
AB  - OBJECTIVE: This study was undertaken to develop and test a 3-dimensional (3D)
      color thickness mapping technique on levator ani imaged with magnetic resonance
      imaging (MRI). METHODS: Supine MRI datasets from 30 women were studied: 10
      asymptomatic, 10 with urodynamic stress incontinence, and 10 with pelvic organ
      prolapse. Levators were manually outlined, and thickness mapping applied. Three
      dimensional models were colored topographically, reflecting levator thickness.
      Thickness and occurrences of absent levator substance (gaps) were compared across
      the 3 groups, using nonparametric statistical tests. RESULTS: Color thickness
      mapping was successful in all subjects. There were statistically significant
      differences in thickness and gap percentages among the 3 groups of women, with
      thicker, bulkier levators in asymptomatic women, compared with women with
      prolapse or urodynamic stress incontinence. CONCLUSION: Color thickness mapping
      is feasible. It may be used to compare levators in symptomatic and asymptomatic
      women, to study relationships between levator thickness and pelvic floor
      dysfunction. This technique can be used in larger studies for hypothesis testing.

PMID- 15467556
TI  - The Term Breech Trial.

PMID- 15467555
TI  - Outcomes of children at 2 years after planned cesarean birth versus planned
      vaginal birth for breech presentation at term: the International Randomized Term
      Breech Trial.
AB  - OBJECTIVE: The purpose of this study was to determine whether planned cesarean
      delivery for the singleton fetus in breech presentation at term reduces the risk
      of death or neurodevelopmental delay at 2 years of age. STUDY DESIGN: In selected
      centers in the Term Breech Trial, children were screened for abnormalities at >
      or =2 years of age with the Ages and Stages Questionnaire, followed by a
      neurodevelopmental assessment if the Ages and Stages Questionnaire score was
      abnormal. RESULTS: A total of 923 of 1159 children (79.6%) from 85 centers were
      followed to 2 years of age. The risk of death or neurodevelopmental delay was no
      different for the planned cesarean than for the planned vaginal birth groups (14
      children [3.1%] vs 13 children [2.8%]; relative risk, 1.09; 95% CI, 0.52- 2.30; P
      = .85; risk difference, +0.3%; 95% CI, -1.9%, +2.4%). CONCLUSION: Planned
      cesarean delivery is not associated with a reduction in risk of death or
      neurodevelopmental delay in children at 2 years of age.

PMID- 15467557
TI  - Randomized trial of McRoberts versus lithotomy positioning to decrease the force
      that is applied to the fetus during delivery.
AB  - OBJECTIVE: In an effort to reduce shoulder dystocia incidence and morbidity, some
      obstetricians use prophylactic maternal hip hyperflexion (McRoberts maneuver),
      with the hope of facilitating delivery and decreasing the traction needed for
      delivery. The objective of this study was to evaluate whether the delivery force
      is reduced with the prophylactic McRoberts maneuver in a prospective, objective
      manner. STUDY DESIGN: Between April 2002 and July 2003, we randomly assigned
      multiparous women with term, cephalic singleton gestations to delivery in the
      lithotomy or McRoberts position. A single physician used a force-measuring system
      that consisted of a custom glove with force sensors to record the amount of force
      that was exerted on the fetal head. The primary outcomes of the study were peak
      force (pounds; highest force needed to accomplish entire delivery), peak force
      for delivery of anterior shoulder (pounds), and peak force rate (pounds per
      second; the duration required to reach the peak force). RESULTS: The peak force
      was not different between the patients in the lithotomy position (n=13) versus
      the McRoberts position (n=14; 7.2 +/- 0.8 lbs vs 8.0 +/- 0.7 lbs; P = .5). The
      peak force for delivery of the anterior shoulder (6.7 +/- 0.8 lbs vs 7.1 +/- 0.7
      lbs; P = .7) and peak force rate (32.3 +/- 7.0 lbs/sec vs 29.1 +/- 3.5 lbs/sec; P
      = .7) were not different between the patients in the lithotomy position versus
      the McRoberts position, respectively. There was no difference between the groups
      for gestational age, birth weight, incidence of diabetes mellitus, or operative
      vaginal delivery. The subjective degree of difficulty of the delivery correlated
      with the peak force (R2 = 0.53; P = .001). CONCLUSION: The use of the McRoberts
      maneuver before clinical diagnosis of shoulder dystocia provides no reduction in
      the force that is used in traction on the fetal head during vaginal delivery in
      multiparous patients. The acceptance of this maneuver to be used prophylactically
      requires re-evaluation.

PMID- 15467558
TI  - ST segment analysis of the fetal electrocardiogram plus electronic fetal heart
      rate monitoring in labor and its relationship to umbilical cord arterial blood
      gases.
AB  - OBJECTIVE: This study was undertaken to determine the ability of intrapartum
      electronic fetal heart rate monitoring (EFM) plus fetal electrocardiogram (ECG)
      ST segment automated ANalysis (STAN, Neoventa Medical, Goteborg, Sweden)
      monitoring to predict metabolic acidemia (defined as an umbilical cord artery pH
      < 7.15 and base deficit > or = 12 mmol/L) at birth. STUDY DESIGN: Women with
      singleton, term pregnancies who had a clinical indication for internal EFM with a
      fetal scalp electrode were included in the study. Attending physicians were
      blinded to the ST analysis information, only using available EFM as per current
      clinical practice. After delivery, 2 trained observers blinded to neonatal
      outcome and ST analysis information performed visual classification of the EFM
      tracing in 10-minute epochs according to FIGO guidelines. ST events automatically
      detected by the STAN S21 monitor (Neoventa Medical) were combined with the visual
      EFM classification as per STAN clinical guidelines (Neoventa Medical). RESULTS:
      When applying STAN clinical guidelines from a sample of 143 women, our data
      indicated a sensitivity of 43%, specificity of 74%, negative predictive value of
      96%, and a positive predictive value of 8% for metabolic acidemia at birth. Poor
      ECG quality, despite good EFM tracings (ECG signal loss), occurred 11% of the
      tracing time. CONCLUSION: The STAN clinical guidelines have a poor positive
      predictive value and a sensitivity of less than 50% for metabolic acidemia at
      birth.

PMID- 15467559
TI  - Randomized clinical trial of intra-anal electromyographic biofeedback
      physiotherapy with intra-anal electromyographic biofeedback augmented with
      electrical stimulation of the anal sphincter in the early treatment of postpartum
      fecal incontinence.
AB  - OBJECTIVE: The purpose of this study was to compare intra-anal electromyographic
      biofeedback alone with intra-anal biofeedback that was augmented with electrical
      stimulation of the anal sphincter in the treatment of postpartum fecal
      incontinence. A secondary aim was to examine the impact of the treatment on
      continence-related quality of life. STUDY DESIGN: Sixty symptomatic women were
      assigned randomly to receive intra-anal electromyographic biofeedback or
      electrical stimulation of the anal sphincter once weekly for 12 weeks and to
      perform daily pelvic floor exercises between treatments. Therapeutic response was
      evaluated with a symptom questionnaire to determine continence score, anal
      manometry, and endoanal ultrasound scanning. Quality of life was assessed before
      and after treatment with a validated questionnaire. RESULTS: Fifty-four women
      completed the treatment; 52 women (96%) had ultrasonic evidence of an external
      anal sphincter defect. After the treatment, both groups demonstrated significant
      improvement in continence score (P < .001) and in squeeze anal pressures (P <
      .04). Resting anal pressures did not alter significantly. Quality of life
      improved after the completion of physiotherapy, but there were no differences in
      outcome between intra-anal electromyographic biofeedback and electrical
      stimulation of the anal sphincter. CONCLUSION: Intra-anal electromyographic
      biofeedback therapy was associated with improved continence and quality of life
      in women with altered fecal continence after delivery. The addition of electrical
      stimulation of the anal sphincter did not enhance symptomatic outcome.

PMID- 15467560
TI  - The continuing effectiveness of active management of first labor, despite a
      doubling in overall nulliparous cesarean delivery.
AB  - OBJECTIVE: The purpose of this study was to determine the continuing
      effectiveness of active management of labor, a protocol that involves early
      detection and correction of dystocia with oxytocin in spontaneous cephalic
      nulliparous labor, by analysis of the contribution of this cohort to a doubled
      overall nulliparous cesarean delivery rate. STUDY DESIGN: This was a
      retrospective analysis of annually collated institutional data on cesarean
      delivery and perinatal outcome. RESULTS: From 1989 to 2000, 81,855 women were
      delivered at the National Maternity Hospital, of whom 34,201 women (42%) were
      nulliparous; the annual proportion of nulliparous women in spontaneous labor
      decreased progressively from 83% to 60%; the overall nulliparous cesarean rate
      increased from 8.1% to 16.6%. Cesarean birth rate among nulliparous women in
      spontaneous labor, although showing a significant upward trend between 1989 and
      2000 (2.4%-4.8%; P = .001), was stable, averaging 5% for the last 8 years (P =
      .705); the peripartum death rate in this group fell significantly (P = .024).
      Comparing results for 1989 with results for 2000, nulliparous women in
      spontaneous labor accounted for 14% of the overall increase in cesarean
      deliveries (dystocia, 5%), compared with 51% for nulliparous women with induced
      labor. The perinatal mortality rate in term infants was unchanged. CONCLUSION:
      Active management of spontaneous first labors remains an effective protocol for
      the promotion of vaginal delivery with low peripartum mortality rates; factors
      other than dystocia in spontaneous labor account for the progressive increase in
      the nulliparous cesarean delivery rate.

PMID- 15467561
TI  - Factors predictive of failed operative vaginal delivery.
AB  - OBJECTIVE: The purpose of this study was to determine what factors are
      independently associated with an increased likelihood of failed operative vaginal
      delivery. STUDY DESIGN: We conducted a population-based case-control study
      evaluating maternal, pregnancy, provider, care setting, and fetal factors
      associated with failed operative vaginal delivery. Subjects were identified using
      Washington state birth certificates for infants born between 1992 and 2001. Cases
      (n = 1750) were live-born singletons with both labored cesarean delivery and an
      operative vaginal delivery ("failure") coded on the birth certificate. Controls
      (n = 3500), frequency matched by delivery year to the cases, were randomly
      selected from among singletons undergoing a successful operative vaginal
      delivery. Odds ratios (OR) and associated 95% CI, estimated with Mantel-Haenszel
      methods, measured the association between case status and potential risk factors.
      RESULTS: Failed operative vaginal delivery was associated with increased maternal
      age, African American race, higher body mass index (BMI), diabetes,
      polyhydramnios, induction of labor, dysfunctional labor, and prolonged labor.
      Case compared with control mothers were more likely to deliver a low-birth weight
      or macrosomic infant. CONCLUSION: Identification of maternal and fetal factors
      associated with failed operative vaginal delivery may enable providers to better
      counsel patients, and allow improved planning and allocation of surgical
      resources.

PMID- 15467562
TI  - Effect of epidural anaesthesia on clinician-applied force during vaginal
      delivery.
AB  - OBJECTIVE: Epidural anesthesia (EA) is used in 80% of vaginal deliveries and is
      linked to neonatal and maternal trauma. Our objectives were to determine (1)
      whether EA affected clinician-applied force on the fetus and (2) whether this
      force influenced perineal trauma. STUDY DESIGN: After informed consent,
      multiparas with term, cephalic, singletons were delivered by 1 physician wearing
      a sensor-equipped glove to record force exerted on the fetal head. Those with EA
      were compared with those without for delivery force parameters. Regression
      analysis was used to identify predictors of vaginal laceration. RESULTS: The
      force required for delivery was greater in patients with EA (n = 27) than without
      (n = 5) (P < .01). Clinical parameters, including birth weight (P = .31) were
      similar between the groups. Clinician force was similar in those with no versus
      first- versus second-degree laceration (P = .5). Only birth weight was predictive
      of laceration (P = .02). CONCLUSION: Epidural use resulted in greater clinician
      force required for vaginal delivery of the fetus in multiparas, but this force
      was not associated with perineal trauma.

PMID- 15467563
TI  - Operative vaginal delivery: a comparison of forceps and vacuum for success rate
      and risk of rectal sphincter injury.
AB  - OBJECTIVE: We investigated the success rate of operative vaginal delivery and
      risk of rectal sphincter injury when forceps or vacuum was used. STUDY DESIGN:
      Cases were identified by a retrospective review of delivery logbooks and an
      obstetric database. Rotations were excluded. Failure was defined as inability to
      deliver the fetus with the initial instrument. Rectal injury was defined as third
      or fourth-degree laceration. Institutional review board approval was obtained. P
      value of less than .05 was considered significant, and odds ratios (OR) were
      calculated when appropriate. RESULTS: Data were obtained for 1802 deliveries:
      1438 occiput anterior and 364 occiput posterior positions. For occiput anterior
      position, rectal sphincter injury with forceps was 53.8% and vacuum 26.6% (P <
      .0001, OR 3.25). Failure rate with vacuum was 6.3% and forceps 0.9% (P < .0001,
      OR 7.53). For occiput posterior position, rectal injury with forceps was 71.6%
      and vacuum 33.1% (P < .0001; OR 5.25). Failure rate with vacuum was 33.0% and
      with forceps 13.6% (P < .0001, OR 3.15). For occiput posterior position, failure
      rate at mid position with vacuum was 71.4%, and forceps 16.7% (P < .001, OR
      12.5). Failure rate at low position with vacuum was 30.8%, and forceps 12.5% (P <
      .001, OR 3.14). Failure rate with vacuum at mid position was higher than at low
      position (P < .0001, OR 5.57). Failure rate with forceps at mid and low positions
      was not significantly different. There was no difference in failure rate between
      vacuum and forceps at the outlet position. CONCLUSIONS: For both occiput anterior
      and posterior cases, the use of forceps was associated with a higher success rate
      than the vacuum, but with greater risk of rectal sphincter injury. The use of
      either vacuum or forceps from the occiput posterior position was associated with
      a higher likelihood of rectal injury and lower likelihood of vaginal delivery
      when compared with the occiput anterior position.

PMID- 15467564
TI  - Episiotomy versus fetal manipulation in managing severe shoulder dystocia: a
      comparison of outcomes.
AB  - OBJECTIVE: In severe shoulder dystocia, when initial maneuvers fail, either
      episiotomy or fetal manipulation (Rubin, Woods' screw, or posterior arm release)
      is recommended. We sought to compare maternal and neonatal outcomes between
      severe shoulder dystocia deliveries managed with episiotomy versus fetal
      manipulation. STUDY DESIGN: We identified severe shoulder dystocia deliveries
      from three databases: all shoulder dystocia deliveries (1993-2003 and 1994-1997)
      from two teaching institutions and litigated cases of shoulder dystocia
      associated permanent brachial plexus palsy from multiple U.S. institutions. Pair
      wise comparisons were made among three groups of deliveries: those managed by
      fetal manipulation without episiotomy (fetal manipulation-only), those managed by
      episiotomy without fetal manipulation (episiotomy-only), and those managed with
      both (episiotomy + fetal manipulation). Rates of brachial plexus palsy, neonatal
      depression, and anal sphincter trauma were compared among groups using chi 2 ,
      with significance at P < .05. RESULTS: Among episiotomy-only, 13 of 22 (59.1%)
      sustained brachial plexus palsy, compared with 20 of 57 (35.1%) among fetal
      manipulation-only (P = .05). Twenty-eight of 48 (58.3%) in episiotomy + fetal
      manipulation had brachial plexus palsy, which did not differ from episiotomy-only
      (P = .95) but was higher than fetal manipulation-only (P = .02), suggesting that
      the addition of episiotomy conferred no benefit in averting neonatal injury. Anal
      sphincter trauma was significantly more common among episiotomy-only and
      episiotomy + fetal manipulation, compared with fetal manipulation-only.
      CONCLUSION: In severe shoulder dystocia, if fetal manipulation can be performed
      without episiotomy, severe perineal trauma can be averted without incurring
      greater risk of brachial plexus palsy.

PMID- 15467565
TI  - Maternal outcomes at 2 years after planned cesarean section versus planned
      vaginal birth for breech presentation at term: the international randomized Term
      Breech Trial.
AB  - OBJECTIVE: This study was undertaken to compare maternal outcomes at 2 years
      postpartum after planned cesarean section and planned vaginal birth for the
      singleton fetus in breech presentation at term. STUDY DESIGN: In selected centers
      in the Term Breech Trial, mothers completed a structured questionnaire at 2 or
      more years postpartum to determine their health in the previous 3 to 6 months.
      RESULTS: A total of 917 of 1159 (79.1%) mothers from 85 centers completed a
      follow-up questionnaire at 2 years postpartum. There were no differences between
      groups in breast feeding, relationship with child or partner, pain, subsequent
      pregnancy, incontinence, depression, urinary, menstrual or sexual problems,
      fatigue, or distressing memories of the birth experience. Planned cesarean
      section was associated with a higher risk of constipation (P = .02). CONCLUSION:
      Maternal outcomes at 2 years postpartum are similar after planned cesarean
      section and planned vaginal birth for the singleton breech fetus at term.

PMID- 15467566
TI  - Obstetric outcomes associated with increase in BMI category during pregnancy.
AB  - OBJECTIVE: The purpose of this study was to investigate effect of increase in
      body mass index (BMI) category on obstetric outcomes. STUDY DESIGN: A cohort
      study was conducted from 1999 to 2002. Women with singleton pregnancies were
      placed in standard BMI categories. Increase in BMI was calculated as difference
      between initial BMI and delivery BMI. ANOVA was used to compare continuous
      variables, and chi-square test for categorical variables. RESULTS: This study
      included 5131 women: 49.8% had no change in BMI category, 43.9% increased by 1
      BMI category, and 6.3% by >1 category. Increase in BMI category was associated
      with higher rates of gestational diabetes (P = .005), failed induction (P <
      .001), lacerations (P < .001), cesarean deliveries (P < .001), and postpartum
      infection (P = .007) in normal weight women. Overweight women also had increased
      rates of preeclampsia (P = .002) and operative vaginal deliveries (P < .001).
      Obese women had higher rates of chorioamnionitis (P = .003), failed induction (P
      < .001), and cesarean deliveries (P = .016). CONCLUSION: Increase in BMI category
      is associated with increased risk of complications.

PMID- 15467567
TI  - How long is too long: Does a prolonged second stage of labor in nulliparous women
      affect maternal and neonatal outcomes?
AB  - OBJECTIVE: The purpose of this study was to examine maternal and neonatal
      outcomes in relation to lengthening intervals of the second stage of labor. STUDY
      DESIGN: This is a retrospective cohort study of 15,759 nulliparous, term,
      cephalic, singleton births at the University of California, San Francisco,
      between 1976 and 2001. The second stage of labor was divided into 1-hour
      intervals. Maternal and neonatal outcomes were compared with the use of chi
      squared and Student t tests, and a probability value of < or =.05 was used to
      indicate statistical significance. Potential confounders were controlled for with
      multivariate logistic regression. RESULTS: Increasing rates of cesarean delivery,
      operative vaginal delivery, and perineal trauma were associated with the second
      stage beyond the first hour. In multivariate analysis, the >4-hour interval group
      had higher rates of cesarean delivery (odds ratio, 5.65; P < .001), operative
      vaginal deliveries (odds ratio, 2.83; P < .001), 3rd- or 4th-degree perineal
      lacerations (odds ratio, 1.33; P = .009), and chorioamnionitis (odds ratio, 1.79;
      P < .001). There were no differences in neonatal acid-base status associated with
      length of second stage. However, there were fewer neonates with a 5-minute Apgar
      score of <7 (odds ratio, 0.45; P = .01). CONCLUSION: Although the length of the
      second stage of labor is not associated with poor neonatal outcome, a prolonged
      second stage is associated with increased maternal morbidity and operative
      delivery rates.

PMID- 15467568
TI  - The continuum of maternal morbidity and mortality: factors associated with
      severity.
AB  - OBJECTIVE: The goal of this study was to examine whether sociodemographic,
      clinical, and other service-related factors, as well as preventability issues
      affect a woman's progression along the continuum of morbidity and mortality.
      STUDY DESIGN: This was a case-control study of pregnancy-related deaths, women
      with near-miss morbidity, and those with other severe, but not life threatening,
      morbidity. Factors associated with maternal outcome were examined. RESULTS:
      Provider factors (related to preventability) and clinical diagnosis were
      significantly associated with progression along the continuum after controlling
      for sociodemographic characteristics (P < .01 for both associations). CONCLUSION:
      In order to improve mortality rates, we must understand maternal morbidity and
      how it may lead to death. This study shows that important initiatives include
      addressing preventability, in particular, provider factors, which may play a role
      in moving women along the continuum of morbidity and mortality.

PMID- 15467569
TI  - Higher rates of tachysystole among patients with clinically apparent uterine
      leiomyomas.
AB  - OBJECTIVE: This study was undertaken to determine uterine and fetal heart rate
      (FHR) tracing patterns associated with clinically apparent uterine leiomyomas.
      STUDY DESIGN: Uterine and FHR patterns of 44 women with diagnosed uterine
      leiomyomas were compared with 601 tracings of controls. Tracings were interpreted
      during the first stage of labor, using the National Institute of Child Health and
      Human Development Research Planning Workshop guidelines. Stratified analysis that
      used the Mantel-Haenszel technique was performed to control for confounders.
      RESULTS: Patients with leiomyomas had higher rates of uterine tachysystole as
      compared with those without leiomyomas (22.7% vs 1.3%; odds ratio [OR] = 21.8,
      95% CI 7.4-65.6; P < .001). No significant differences were noted between the
      groups regarding FHR patterns. Higher rates'of prostaglandin induction and
      oxytocin augmentation were noted in the uterine leiomyomas group (6.8% vs 0.8%; P
      = .005 and 52.3% vs 10.5%; P < .001, respectively). However, controlling for
      prostaglandin induction and oxytocin augmentation, with the use of the Mantel
      Haenszel procedure, did not change the significant association between uterine
      leiomyomas and tachysystole (weighted OR 12.5, 95% CI 6.2-75.1, and weighted OR
      8.7, 95% CI 3.6-43.1, respectively). CONCLUSION: Clinically apparent uterine
      leiomyomas, although not coupled with abnormal FHR patterns, are associated with
      higher rates of tachysystole.

PMID- 15467570
TI  - Diurnal glycemic profile in obese and normal weight nondiabetic pregnant women.
AB  - OBJECTIVE: A paucity of data exists concerning the normal glycemic profile in
      nondiabetic pregnancies. Using a novel approach that provides continuous
      measurement of blood glucose, we sought to evaluate the ambulatory daily glycemic
      profile in the second half of pregnancy in nondiabetic women. STUDY DESIGN: Fifty
      seven obese and normal weight nondiabetic subjects were evaluated for 72
      consecutive hours with continuous glucose monitoring by measurement interstitial
      glucose levels in subcutaneous tissue every 5 minutes. Subjects were instructed
      not to modify their lifestyle or to follow any dietary restriction. For each
      woman, mean and fasting blood glucose values were determined; for each meal
      during the study period, the first 180 minutes were analyzed. RESULTS: For the
      study group, the fasting blood glucose level was 75 +/- 12 mg/dL; the mean blood
      glucose level was 83.7 +/- 18 mg/dL; the postprandial peak glucose value level
      was 110 +/- 16 mg/dL, and the time interval that was needed to reach peak
      postprandial glucose level was 70 +/- 13 minutes. A similar postprandial glycemic
      profile was obtained for breakfast, lunch, and dinner. Obese women were
      characterized by a significantly higher postprandial glucose peak value,
      increased 1- and 2-hour postprandial glucose levels, increased time interval for
      glucose peak, and significantly lower mean blood glucose during the night. No
      difference was found in fasting and mean blood glucose between obese and nonobese
      subjects. CONCLUSION: Glycemic profile characterization in both obese and normal
      weight nondiabetic subjects provide a measure for the desired level of glycemic
      control in pregnancy that is complicated with diabetes mellitus.

PMID- 15467571
TI  - The impact of maternal obesity and weight gain on vaginal birth after cesarean
      section success.
AB  - OBJECTIVE: This study was undertaken to determine the impact of maternal obesity
      on success of a trial of labor (vaginal birth after cesarean section [VBAC])
      after a single low transverse cesarean delivery. STUDY DESIGN: Individual charts
      of women with low transverse cesarean delivery in their first viable pregnancy
      who underwent a VBAC in their second viable pregnancy at our urban tertiary care
      institution were reviewed. Maternal body mass index (BMI) was classified as
      underweight (<19.8 kg/m2), normal (19.8-24.9 kg/m2), overweight (25-29.9 kg/m2),
      or obese (> or =30 kg/m2). Clinical characteristics and labor outcomes were
      assessed. Factors potentially affecting VBAC success were analyzed by univariate
      analysis. Logistic regressions were performed to determine the impact of maternal
      pregravid BMI on VBAC success after controlling for confounding factors. RESULTS:
      Of 510 women attempting a trial of labor, 337 (66%) were successful and 173 (34%)
      failed VBAC. Decreased VBAC success was seen in obese (54.6%) but not overweight
      (65.5%) women compared with women of normal BMI (70.5%), P = .003 and .36,
      respectively. Underweight women had more VBAC success than women of normal BMI
      (84.7% vs 70.5%, P = .04). Controlling for other factors, the association between
      increasing pregravid BMI and BMI > or =30 kg/m 2 with decreased VBAC success
      persisted, P = .03 and .006, respectively. Normal BMI women who became overweight
      before the second pregnancy had decreased VBAC success compared with those whose
      BMI remained normal (56.6% vs 74.2%, P = .006). However, overweight women who
      decreased their BMI to normal before the second pregnancy did not significantly
      improve VBAC success (64.0% vs 58.4%, P = .67). CONCLUSION: Increasing pregravid
      BMI and weight gain between pregnancies reduce VBAC success after a single low
      transverse cesarean delivery.

PMID- 15467572
TI  - Risk of cesarean wound complications in diabetic gestations.
AB  - OBJECTIVE: This study was undertaken to examine the association between
      pregestational diabetes mellitus (DM) and wound complications after cesarean
      delivery (CD). STUDY DESIGN: This was a retrospective, observational cohort study
      in patients with type 1 and 2 DM compared with non-DM controls undergoing CD.
      Wound complications were defined as wound infection, wound separation greater
      than 1 cm, and wound dehiscence. RESULTS: There was an overall incidence of wound
      complications of 18.4% (34/185) in DM versus 5.8% (10/174) in non-DM (unadjusted
      odds ratio of 3.7; 95% CI = 1.8-7.7). Mean body mass index before pregnancy was
      30.9 in DM versus 26.5 kg/m 2 in non-DM (P < .01). A multivariable logistic
      regression model adjusting for body mass index, length of surgery, and previous
      CD demonstrated a 2.5-fold increased risk of wound complications in DM patients
      compared with non-DM patients (95% CI = 1.1-5.5). CONCLUSION: Pregestational
      diabetes is associated with a 2.5-fold increase in wound complications after CD.

PMID- 15467573
TI  - The influence of obesity and diabetes on the prevalence of macrosomia.
AB  - OBJECTIVE: This study was undertaken to determine the relative contribution of
      abnormal pregravid maternal body habitus and diabetes on the prevalence of large
      for-gestational-age infants. STUDY DESIGN: Maternal and neonatal records for
      singleton term (> or =37 weeks' estimated gestational age) deliveries January
      1997 through June 2001 were reviewed. Subjects were characterized by pregravid
      body mass index (BMI), divided into underweight (BMI <19.8 kg/m2), normal (BMI
      19.8-25 kg/m2), overweight (BMI 25.1-30 kg/m2), and obese (BMI >30 kg/m2)
      subgroups. Diabetes was classified as gestational, treated with diet alone
      (A1GDM), or with insulin (A2GDM), and pregestaional diabetes (PDM). Newborn
      weight greater than the 90th percentile for gestational age, based on published
      local birth weight data, defined large for gestational age (LGA). The risk of LGA
      delivery for underweight, overweight, and obese women were compared with that of
      women with normal pregravid BMI. Multiple regression models, including parity,
      newborn sex, BMI, race, and diabetes, were constructed to examine the relative
      effect of abnormal BMI and diabetes on the risk of the delivery of an LGA infant.
      RESULTS: Complete data for 12,950 deliveries were included (1,640 [13.0%]
      underweight, 2,991 [23.7%] overweight, and 2,928 [23.2%] obese). LGA delivery
      affected 11.8% of the study sample; 303 (2.3%) of subjects had A1GDM, whereas 94
      (0.7%) had A2GDM, and 133 (1.6%) had PDM. Compared with normal BMI subjects,
      obese women were at elevated risk for LGA delivery (16.8% vs 10.5%; P < .0001) as
      were overweight women (12.3% vs 10.5%; P = .01). Diabetes was also a risk factor
      for LGA delivery (A1GDM: [29.4% vs 11.4%]; A2GDM: [29.8% vs 11.7%]; PDM: [38.3%
      vs 11.6%]; P < .0001 for each). Other risk factors for LGA delivery included
      parity (13.2% vs 9.5%; P < .0001), and male gender (14.3% vs 9.3%; P < .0001).
      Black race and low pregravid BMI were associated with a lower risk of LGA
      delivery (9.0% vs 13.7%; P < .0001) and (6.4% vs 10.5%; P = .006), respectively.
      Multiple regression revealed the independent influence of pregravid obesity and
      PDM, increasing the risk of LGA delivery (BMI >30kg/m 2 [Adjusted odds ratio
      (AOR) = 1.6]), and PDM (AOR = 4.4). CONCLUSION: Obesity and pregestational
      diabetes are independently associated an increased risk of LGA delivery. The
      impact of abnormal body habitus on birth weight grows as BMI increases. Diabetes
      has the greatest affect on the normal and underweight population. With the
      increasing prevalence and relative frequency of overweight and obese women in
      pregnancy compared with diabetes (46.7% vs 4.1%), abnormal maternal body habitus
      exhibits the strongest influence on the prevalence of LGA delivery in our
      population.

PMID- 15467574
TI  - The influence of obesity and diabetes on the risk of cesarean delivery.
AB  - OBJECTIVE: To determine the influence of pregravid obesity and diabetes on
      cesarean delivery (CD) risk. STUDY DESIGN: Women with singleton pregnancies of 23
      weeks or more estimated gestational age who were undergoing a trial of labor
      January 1997 through June 2001 were categorized by pregravid body mass index
      (underweight [<19.8 kg/m 2 ], normal [19.8-25 kg/m 2 ], overweight [25.1-30
      kg/m2], obese [>30 kg/m2]). Diabetes (DM) was divided into categories of
      gestational, treated with diet modification (A1GDM) or insulin (A2GDM), and
      pregestational (PDM). Prior CDs were excluded. CD rates for each group were
      compared in univariate analyses stratified by estimated gestational age (term,
      preterm, total). Other variables examined included DM, macrosomia (birth weight
      4500 g or more), induction, and parity. Multiple regression included significant
      variables to predict the influence of diabetes and obesity on CD risk. RESULTS:
      Records for 12,303 deliveries were evaluated (obese: 2828 [22.9%]; overweight:
      2605 [21.2%]; A1GDM: 270 [2.2%]; A2GDM: 93 [0.8%]; PDM: 126 [1%]). Obese and
      overweight subjects had a higher risk for CD, compared with normal subjects
      (13.8% and 10.4% versus 7.7%, P < .0001 for each). Other CD risk factors were
      macrosomia (25% versus 9.4%), nulliparity (16.5% versus 4.7%), induction (17.4%
      versus 8.3%), diabetes (A1GDM: 16.7% versus 9.4%; A2GDM: 24.7% versus 9.5%; PDM:
      34.9% versus 9.3%) and black race (10.7% versus 8.8%) ( P < .0001 for each). In
      multiple regression models including term deliveries, obesity and PDM were
      independent CD risk factors ([adjusted OR overweight: 1.5, P < .0001; adjusted OR
      PDM: 2.9, P = .01]; [adjusted OR obese: 2.4, P < .0001, PDM: 2.9, P = .0002]).
      CONCLUSION: Pregravid obesity and diabetes independently increase the risk for
      CD. Given the disparate prevalence of obesity and diabetes in the United States,
      body habitus has a significantly larger impact on CD risk.

PMID- 15467575
TI  - First- and second-trimester ultrasound assessment of gestational age.
AB  - OBJECTIVE: The purpose of this study was to evaluate and compare the accuracy of
      first- and second-trimester ultrasound assessment of fetal age. STUDY DESIGN:
      Differences between ultrasound estimated gestational age and true gestational age
      were calculated between 11 to 14 weeks of gestation and 18 to 22 weeks of
      gestation for singleton, twin, and triplet pregnancies that were conceived by in
      vitro fertilization. RESULTS: One hundred four singleton pregnancies, 81 twin
      pregnancies, and 33 triplet pregnancies were included. First trimester ultrasound
      estimates overestimated gestational age by a mean (+/- SEM) of 1.3 +/- 0.2 days
      (P < .0001) for singleton pregnancies, 1.4 +/- 0.2 days (P < .0001) for twin
      pregnancies, and 0.8 +/- 0.4 days (P = .027) for triplet pregnancies. Second
      trimester estimates were underestimated by a mean of -0.1 +/- 0.4 days (P = .87)
      for singletons, -0.6 +/- 0.3 days (P = .083) for twins, and -0.6 +/- 0.5 days (p
      = 0.21) for triplets. CONCLUSION: Ultrasound assessment of gestational age is
      very accurate and is marginally better in the first trimester compared with the
      second.

PMID- 15467576
TI  - Fetal transcerebellar diameter measurement with particular emphasis in the third
      trimester: a reliable predictor of gestational age.
AB  - OBJECTIVE: The purpose of this study was to validate prospectively a previous
      retrospectively established nomogram for the prediction of gestational age using
      transcerebellar diameter, especially in the third trimester. STUDY DESIGN: In a
      previous study, we retrospectively constructed a cross-sectional nomogram using
      transcerebellar diameter measurements in 24,026 well-dated singleton fetuses. In
      the present study, this nomogram was validated prospectively on the basis of
      patients who were seen between August 2002 and May 2003 and who were carrying non
      anomalous and non-malformed singleton gestations between 14 and 42 weeks (n =
      2597 gestations). The actual gestational age was then subtracted from the
      predicted gestational age, and the concordance between actual and predicted
      gestational ages was assessed based on the Pearson correlation (r). RESULTS:
      Concordance between the actual and predicted gestational age was high (r = 0.92;
      P < .0001). This agreement was superior in the second trimester (r = 0.93; P <
      .0001) than in the third trimester (r = 0.81; P < .001). Between 17 and 21 weeks,
      and between 22 and 28 weeks of gestation, the predicted gestational age ranged
      between 0 and 4 days, and between 0 and 2 days, respectively, of actual
      gestational age. Between 29 and 36 weeks of gestation, predicted gestational age
      was within 5 days of actual gestational age; at 37 weeks of gestation, the
      predicted gestational age was discrepant by 9 days. CONCLUSION: This prospective
      study demonstrates that transcerebellar diameter measurement is an accurate
      predictor of gestational age, even in the third trimester of pregnancy.

PMID- 15467578
TI  - Morbidity that is associated with curettage for the management of spontaneous and
      induced abortion in women who are infected with HIV.
AB  - OBJECTIVE: The purpose of this study was to determine the morbidity that is
      associated with curettage for the management of abortions in women who were
      infected with human immunodeficiency virus compared with women who were not
      infected with human immunodeficiency virus. STUDY DESIGN: Women who were infected
      with human immunodeficiency virus (cases) and who underwent curettage for the
      management of scheduled and unscheduled abortions in the first half of pregnancy
      between January 1, 1993, and December 31, 2002, were identified. Women who were
      not infected with human immunodeficiency virus (control subjects) were matched
      3:1 to cases for gestational age, type of abortion, and year of procedure.
      Medical records were reviewed to obtain demographic characteristics, gestational
      age, abortion characteristics, and procedure-related complications. Chi-squared
      test, Student t test, and Wilcoxon rank-sum test were used to determine
      statistical significance. RESULTS: Seventy-one women who were infected with human
      immunodeficiency virus (cases) and 213 women who were not infected with human
      immunodeficiency virus (control subjects) who underwent curettage during the
      study period were evaluated. Forty-eight cases (68%) and 146 control subjects
      (69%) underwent a scheduled curettage. Twenty-three cases (32%) and 66 control
      subjects (31%) underwent an unscheduled curettage for spontaneous or incomplete
      abortion. No significant differences were seen in age, gravidity, or parity.
      There were significantly more black women in the HIV-infected cohort (P < .001),
      which was representative of our human immunodeficiency virus population. The mean
      gestational age in the cases was greater than in the control subjects (10.9 +/-
      4.2 weeks of gestation vs 9.2 +/- 3.1 weeks of gestation; P = .004). Procedure
      related complications occurred in 10 of the women (14%) who were infected with
      human immunodeficiency virus who underwent curettage, compared with 9 of the
      women (4%) who were not infected with human immunodeficiency virus (P = .004).
      With the use of logistic regression, complication rates were unaffected by the
      difference in gestational age. Infectious complications did not differ between
      the 2 groups (P = .435). CONCLUSION: There was a higher rate of procedure-related
      complications among women who were infected with human immunodeficiency virus and
      who underwent curettage for management of spontaneous and induced abortions.
      There was no increase in infectious morbidity in the women who were infected with
      human immunodeficiency virus.

PMID- 15467577
TI  - Assessing the risk of birth defects associated with antiretroviral exposure
      during pregnancy.
AB  - OBJECTIVE: The purpose of this study was to examine teratogenic risk of
      antiretroviral (ARV) drugs. STUDY DESIGN: The Antiretroviral Pregnancy Registry
      (APR) monitors prenatal exposures to ARV drugs and pregnancy outcome through a
      prospective exposure-registration cohort. Statistical inference uses exact
      methods for binomial proportions. RESULTS: Through July 2003, APR has monitored
      3583 live births exposed to ARV. Among 1391 first trimester exposures, there were
      38 birth defects, prevalence of 2.7% (95% CI 1.9-3.7), not significantly higher
      than the CDC's population surveillance rate, 3.1 per 100 live births (95% CI 3.1
      3.2). For lamivudine, nelfinavir, nevirapine, stavudine, and zidovudine,
      sufficient numbers of live births (>200) following first-trimester exposures have
      been monitored to allow detection of a 2-fold increase in risk of birth defects
      overall; no increases have been detected. CONCLUSION: APR data demonstrate no
      increase in prevalence of birth defects overall or among women exposed to
      lamivudine, nelfinavir, nevirapine, stavudine, and zidovudine.

PMID- 15467579
TI  - Elective cesarean delivery to prevent perinatal transmission of hepatitis C
      virus: a cost-effectiveness analysis.
AB  - OBJECTIVE: This study was undertaken to determine whether elective cesarean
      delivery to avert perinatal hepatitis C virus (HCV) transmission is cost
      effective. STUDY DESIGN: Using decision analysis, we compared 2 approaches: (1)
      offering elective cesarean delivery to avert perinatal HCV transmission, (2)
      performing a cesarean delivery only for obstetric indications. Lifetime cost and
      quality-adjusted-life-years (QALYs) for HCV-infected neonates were evaluated with
      Markov analysis. We assumed elective cesarean delivery reduces perinatal HCV
      transmission, and we varied both the risk reduction caused by elective cesarean
      delivery and the background risk of perinatal HCV infection. RESULTS: When
      elective cesarean section prevents all perinatal HCV transmission, 18 elective
      cesarean deliveries are necessary to avert 1 neonatal infection with a cost
      effectiveness ratio of 34,812 dollars/QALY. At a background perinatal
      transmission rate of 7.7% elective cesarean deliveries is cost-effective only if
      it reduces the risk of perinatal transmission by more than 77%. CONCLUSION:
      Elective cesarean delivery is cost-effective only if it substantially reduces the
      risk of perinatal HCV transmission.

PMID- 15467580
TI  - The impact of protease inhibitors on maternal serum screening analyte levels in
      pregnant women who are HIV positive.
AB  - OBJECTIVE: The purpose of this study was to compare alpha-fetoprotein, human
      chorionic gonadotropin, and unconjugated estriol levels in women who take
      protease inhibitors and those women who do not. STUDY DESIGN: This retrospective
      review from August 2000 to May 2003 was performed for maternal serum screen
      results, medication use, pregnancy, and perinatal outcomes. RESULTS: Thirty-nine
      women met study criteria. Sixteen women were treated with protease inhibitors,
      and 23 women were not treated with protease inhibitors. There was no difference
      in initial viral load or initial CD4 count between the groups. No difference was
      found for human chorionic gonadotropin and estriol levels; significantly lower
      alpha-fetoprotein multiples of the median were found for the women who were
      treated with protease inhibitors compared with the women who were not (0.97 +/-
      0.32 [SD] MoM vs 1.2 +/- 0.4 MoM, respectively; P = .04). Six of 39 women (15%)
      had positive maternal serum screens. All the babies were normal at birth, and
      there were no cases of perinatal transmission of human immunodeficiency virus.
      CONCLUSION: Protease inhibitors are associated with lower alpha-fetoprotein
      levels in women who are infected with human immunodeficiency virus.

PMID- 15467581
TI  - Pregnancy outcome in women with prosthetic heart valves.
AB  - OBJECTIVE: This study was undertaken to evaluate the risks and pregnancy outcome
      in women with prosthetic heart valves on different anticoagulent regimens. STUDY
      DESIGN: A retrospective chart review of 82 pregnancies in 33 women with
      mechanical valve prostheses at a tertiary referral center from 1987 to 2002. The
      main outcome measures were major maternal complications and perinatal outcome.
      RESULTS: The valve replaced was mitral (60.6%), aortic (18.2%), and both (21.2%).
      Fifty-four pregnancies (65.9%) resulted in live births, 9 (11.0%) had stillbirths
      (all on warfarin), and 12 (14.6%) had spontaneous and 7 (8.5%) therapeutic
      abortions (all on warfarin). The rate of spontaneous abortion was highest in
      women on warfarin throughout pregnancy (P < .01). The live birth rate was higher
      in women on heparin compared with those on warfarin (P < .01), and in those on
      heparin/warfarin compared with warfarin alone (P < .01). There were no maternal
      deaths; however, 3 patients had mitral valve thrombosis (2 on heparin and 1 on
      warfarin) necessitating surgery in 1 patient and medical thrombolysis in 2
      patients. Hemorrhagic complications occurred in 5 patients, 4 of whom required
      transfusion. CONCLUSION: No single anticoagulant regimen confers complete
      protection from thromboembolic phenomena in pregnancy. Despite a high maternal
      morbidity rate, the perinatal outcome is acceptable when pregnancy progresses
      beyond the first trimester.

PMID- 15467582
TI  - Prospective echocardiographic evaluation of atrioventricular conduction in
      fetuses with maternal Sjogren's antibodies.
AB  - OBJECTIVE: Fetal complete atrioventricular block (AVB) occurs in 2-5% of
      Sjogren's antibodies (SSA/SSB)-positive pregnancies with substantial morbidity
      and mortality. We evaluated the incidence of 1 degrees and 2 degrees AVB by
      measuring Doppler-derived mechanical PR intervals. STUDY DESIGN: We compared
      mechanical PR intervals of fetuses of SSA/SSB positive mothers referred to a
      single cardiology center between 1997 and 2003 with control fetuses and fetuses
      with 1 degrees or 2 degrees AVB confirmed by magnetocardiography or postnatal
      electrocardiogram. RESULTS: One hundred thirty-nine fetal echocardiograms
      performed on 59 SSA/SSB-positive pregnant women at 24.3 +/- 5.0 weeks gestation
      were compared with 150 controls. Mechanical PR intervals of the study group
      (120.5 +/- 9.8 milliseconds) and controls (120.6 +/- 8.7 milliseconds) were the
      same but differed significantly from fetuses with 1 degrees and 2 degrees AVB
      (191.5 +/- 29.6 msec). CONCLUSION: The incidence of 1 degrees and degrees 2 fetal
      AVB in SSA/SSB-positive pregnancies is low and can be identified by abnormal
      mechanical PR interval.

PMID- 15467583
TI  - Diagnosis of pulmonary embolism: a cost-effectiveness analysis.
AB  - OBJECTIVE: Pulmonary embolism is a major cause of maternal death. The work up for
      suspected pulmonary embolism is complex, with many potential diagnostic options.
      We performed a cost analysis to evaluate which of several diagnostic strategies
      was the most cost-effective with the least number of deaths from pulmonary
      embolism. STUDY DESIGN: We created a decision tree to evaluate the following
      strategies: (1) Compression ultrasonography followed by anticoagulation (if there
      is a positive result) or secondary tests, ventilation perfusion scans or spiral
      computed tomography (if there is a negative result); high probability ventilation
      perfusion scans (a positive test result) resulted in anticoagulation; low
      probability ventilation perfusion scans (a negative test) resulted in no
      treatment; intermediate tests that resulted in a second test (computed tomography
      or pulmonary angiography). (2) Ventilation perfusion scans as a primary test
      followed by anticoagulation. (3) Computed tomography followed by anticoagulation
      (if there is a positive result). The following assumptions were made: The
      incidence of pulmonary embolism in pregnant women with suspected pulmonary
      embolism is 5%; 40% of documented pulmonary embolisms have a positive compression
      ultrasound result; 10% of ventilation perfusion scans for suspected pulmonary
      embolism are high probability, 60% are indeterminate, and 30% are low probability
      for pulmonary embolism; the sensitivity of computed tomography is 95%; the
      sensitivity of angiography is 98%. The assumed mortality rate of treated
      pulmonary embolism is 0.7% and of untreated pulmonary embolism in pregnancy is
      15% (range, 10%-50%). The angiography-associated mortality rate is 0.5%, and the
      anticoagulation associated mortality rate is 0.2%. The following costs were used
      for the model: compression ultrasonography, 200.00 dollars; ventilation perfusion
      scans, 400.00 dollars; angiography, 1000.00 dollars; computed tomography, 500.00
      dollars; and anticoagulation, 5982.00 dollars. With baseline assumptions, spiral
      computed tomography as the initial diagnostic regimen was found to be the most
      cost-effective at 17,208 dollars per life saved. Sensitivity analyses were
      performed over a wide range of assumptions that included alteration of the
      probability of pulmonary embolism, the sensitivity of computed tomography,
      ventilation perfusion scans, and compression ultrasonography, the cost of
      computed tomography, and the mortality rate of untreated pulmonary embolism. Our
      findings remained robust over a wide range of assumptions. CONCLUSION: Suspected
      pulmonary embolism remains a diagnostic quandary. Our analysis indicated that
      spiral computed tomography offers the most cost-effective method for diagnosing
      this potentially fatal condition.

PMID- 15467584
TI  - A prospective trial that demonstrates that dalteparin requirements increase in
      pregnancy to maintain therapeutic levels of anticoagulation.
AB  - OBJECTIVE: The purpose of this study was to determine whether standard
      therapeutic doses of dalteparin maintain peak therapeutic levels of
      anticoagulation during pregnancy. STUDY DESIGN: This was a prospective trial in
      which 13 pregnancies that required therapeutic anticoagulation were treated with
      dalteparin 100 U/kg every 12 hours; peak and trough (predose) low molecular
      weight heparin (anti-Xa activity) levels were monitored every 2 weeks. Dosage
      adjustments were made to maintain peak anti-Xa activity between 0.5 and 1.0
      IU/ml. Bone density and bone turnover markers were measured. RESULTS: A total of
      250 peak and trough low-molecular-weight heparin (LMWH) levels were obtained.
      Eighty-five percent of pregnancies (11/13) required an upward dosage adjustment.
      Trough levels were in the therapeutic range only 9% of the time, despite the
      maintenance of therapeutic peak levels. Bone resorption markers and density were
      unchanged in singleton pregnancies. CONCLUSION: Dalteparin dosing, based on
      weight alone, every 12 hours is inadequate to maintain most pregnant women in the
      therapeutic range throughout pregnancy as measured by anti-Xa activity. Trough
      levels are rarely in the therapeutic range, despite maintenance of therapeutic
      peak levels. These notable changes in low molecular weight heparin peak may
      explain reported failures in pregnancy.

PMID- 15467585
TI  - In utero transplantation of autologous and allogeneic fetal liver stem cells in
      ovine fetuses.
AB  - OBJECTIVE: The purpose of this study was to assess the feasibility of autologous
      stem cell transplantation in fetal sheep and to compare short-term engraftment of
      allogeneic and autologous fetal liver stem cells in an immunocompetent large
      animal model. STUDY DESIGN: Fetal liver stem cells were collected from preimmune
      sheep fetuses with an open or ultrasound-guided technique. After being labeled
      with PKH26, the cells were transplanted intraperitoneally into allogeneic and
      autologous fetal recipients at 48 to 64 days of gestation. Engraftment was
      determined by flow cytometry and real-time polymerase chain reaction 1 to 2 weeks
      after transplantation. RESULTS: Fetal loss rate was 29% (allogeneic
      transplantation) and 73% (autologous transplantation). Engraftment of donor cells
      was found in all fetuses, with a level of < or =4.7% in fetal liver, spleen, bone
      marrow, blood and thymus. Overall, there was no difference between allogeneic and
      autologous grafts. CONCLUSION: Autologous in utero transplantation of fetal liver
      stem cells in fetal sheep is feasible, but yields a high loss rate. Differences
      in the major histocompatibility complex between donor and recipient seems not to
      have a major impact on stem cell engraftment early in gestation; major
      histocompatibility complex-independent donor/host competition might be
      responsible for low engraftment in immunocompetent recipients.

PMID- 15467586
TI  - Prenatal exposure to binge drinking and cognitive and behavioral outcomes at age
      7 years.
AB  - OBJECTIVE: The goal of this study was to examine differential effects of amount
      and pattern of prenatal alcohol exposure on child outcome. STUDY DESIGN: Alcohol
      use was assessed at each prenatal visit, and IQ and behavior were measured at age
      7 years. RESULTS: After control for confounders, the amount of exposure was
      unrelated to IQ score and behavior for >500 black 7-year-old children. However,
      children who were exposed to binge drinking were 1.7 times more likely to have IQ
      scores in the mentally retarded range and 2.5 times more likely to have
      clinically significant levels of delinquent behavior. CONCLUSION: During prenatal
      care, clinicians should attend not only to amount but also to the pattern of
      alcohol intake, because of the elevated risk for cognitive deficits and long-term
      behavioral abnormality.

PMID- 15467587
TI  - Down syndrome births in the United States from 1989 to 2001.
AB  - OBJECTIVE: We investigated the observed and expected Down syndrome livebirths in
      the US from 1989 to 2001. STUDY DESIGN: Using birth certificate data, we recorded
      maternal age-specific live births from 1989 to 2001, and stratified them by women
      15 to 34 and 35 to 49 years old. We estimated Down syndrome live births from 1989
      to 2001, assuming no terminations. We recorded Down syndrome live births by year
      from 1989 to 2001. RESULTS: Despite an expected 1.32-fold increase in Down
      syndrome live birth rates from 1989 to 2001, Down syndrome live births actually
      declined. In 1989, the rate of Down syndrome cases was 15% lower than expected,
      decreasing to 51% by 1998. Women 15 to 34 had 45% fewer affected pregnancies in
      2001, while women 35 to 49 had 53% fewer in 2001. We estimated that Down syndrome
      live births decreased from 3962 in 1989 to 3654 in 2001. CONCLUSION: Down
      syndrome live births declined in the US despite an expected increase caused by
      delayed or extended childbearing.

PMID- 15467588
TI  - A prospective comparison of total protein/creatinine ratio versus 24-hour urine
      protein in women with suspected preeclampsia.

PMID- 15467589
TI  - 2001 consensus guidelines for the management of women with cervical
      intraepithelial neoplasia.

PMID- 15467591
TI  - PKC isoforms in human uterine contractility. Whodunit?

PMID- 15467593
TI  - Accuracy of home pregnancy tests at the time of missed periods.

PMID- 15467592
TI  - The effect of small volume amnioinfusion that resulted in fetal heart rate
      acceleration.

PMID- 15467597
TI  - Proton pump inhibitor therapy for chronic laryngo-pharyngitis: a randomized
      placebo-control trial.
AB  - OBJECTIVE: To determine the efficacy of proton-pump inhibitor (PPI) therapy for
      chronic laryngo-pharyngitis treated with lifestyle modification. STUDY DESIGN AND
      METHODS: Double-blind, randomized trial comparing two-month Rabeprazole (20 mg
      b.i.d.) to placebo control. RESULTS: Compared to baseline, both PPI and control
      patients had significant improvement in total reflux symptoms (P = 0.002 and P =
      0.03 respectively), with significant improvement in "laryngo-pharyngeal" but not
      "typical" reflux symptoms. No significant difference was noted for change in
      reflux symptoms between PPI-treated and control patients (P = 0.44). Significant
      global improvement was noted by 50% of control and 53% of PPI-treated patients (P
      = 1.0). No significant differences were noted within or between treatment groups
      for change in health status or videostrobolaryngoscopy grade. Lifestyle
      modification compliance correlated significantly with global improvement.
      CONCLUSION: Compared to baseline, lifestyle modification for 2 months
      significantly improved chronic laryngo-pharyngitis symptoms. When compared to
      control, treatment with a PPI failed to demonstrate significantly greater
      improvement in reflux symptoms, health status, or laryngeal appearance.

PMID- 15467598
TI  - Vocal fold augmentation with calcium hydroxylapatite.
AB  - OBJECTIVES: Voice disorders affect more than 3% of the general population. Vocal
      fold atrophy is a part of the normal aging process, with up to 60% of 60-year-old
      individuals displaying evidence of glottal insufficiency. A safe, effective, and
      durable substance for injection augmentation of the vocal folds is not currently
      available. The purpose of this investigation was to describe our preliminary
      experience with calcium hydroxylapatite (CaHA) for vocal fold augmentation.
      METHODOLOGY: All patients undergoing injection augmentation of the vocal folds
      with CaHA between January 1, 2002 and June 1, 2003 were prospectively evaluated.
      Data concerning indications, technique, functional outcome, and complications
      were collected. In addition, the larynx donated from a woman who underwent vocal
      fold augmentation with CaHA and subsequently died from terminal cancer was
      histologically examined. RESULTS: A total of 39 vocal folds in 23 individuals
      were injected with CaHA. The mean age of the cohort was 62. Fifty-two percent
      were male. The indications for augmentation were unilateral vocal fold paralysis
      (9/23), unilateral vocal fold paresis (5/23), presbylarynx (3/23), Parkinson's
      (3/23), bilateral vocal fold paresis (2/23), and abductor spasmodic dysphonia
      (1/20). There were no adverse reactions. All individuals reported improvement on
      a self-administered disease-specific outcome measure (P < 0.001). The pathology
      from the donated larynx 3 months after injection revealed intact CaHA spherules
      in good position with a minimal, monocellular inflammatory reaction to the gel
      carrier and no evidence of implant rejection. CONCLUSIONS: Initial experience
      with vocal fold augmentation using CaHA is promising. Long-term safety and
      efficacy needs to be established.

PMID- 15467599
TI  - Complications of metallic stents in the pediatric airway.
AB  - OBJECTIVE: Our aim was to present our experience with complications caused by
      placement of metallic stents in the pediatric airway. DESIGN AND SETTING: We
      conducted a retrospective study of the medical records of patients with
      complications resulting from metallic stent placement, managed by the senior
      authors between 1993 and 2002. RESULTS: Nine children had complications
      associated with the placement of metallic airway stents. Of these, 8 children
      required stent removal. Granulation tissue and tracheal stenosis were seen in all
      7 children with long standing stent placement. There was 1 stent death in this
      series. CONCLUSIONS: Metallic airway stents can cause significant complications
      in the pediatric airway. These complications may supersede the airway compromise
      that necessitated their initial placement. As such, metallic stent placement
      should be approached with caution. The likelihood and severity of complications
      increase with time, as do the difficulties encountered upon removal. The
      proportion of patients in whom metallic stents may be placed "permanently"
      without complications is not known. Therefore we recommend that metallic airway
      stents be considered a temporizing measure of limited duration.

PMID- 15467600
TI  - Transnasal endoscopic repair of choanal atresia: why stent?
AB  - OBJECTIVE: To analyze the outcome of transnasal endoscopic repair of choanal
      atresia in children without stenting. DESIGN: Retrospective review. SETTING:
      Academic pediatric referral center. PATIENTS: Thirteen children ages 2 days to 13
      years old (mean 45 months) who presented with unilateral (8) or bilateral (5)
      choanal atresia and underwent transnasal endoscopic surgery between January 1997
      and May 2002. No stents were used. All patients received combinations of oral
      steroids, topical nasal steroids, and oral antibiotics. Patency was defined as
      less than 50% restenosis. RESULTS: The 4 patients who underwent office serial
      examination alone after surgery remained patent. Seven of the 9 patients who
      underwent reexamination under general anesthesia had varying amounts of emerging
      granulation tissue or minor synechia formation that resolved with microdebrider
      excision. All serial office endoscopies demonstrated no restenoses. No office
      dilations were performed. There were no long-term complications. One patient (2
      days old) who underwent tracheoesophageal fistula repair and bilateral choanal
      atresia repair on the same day required a blood transfusion. Both patients with
      tracheostomies were decannulated. CONCLUSIONS: Transnasal endoscopic repair of
      choanal atresia, both unilateral and bilateral, is safe, and is effective without
      stenting. Postoperative failure of endoscopic approaches may be a result of
      prolonged mucosal trauma from stenting rather than any deficiency inherent in the
      surgical technique. Adjuctive therapy may not offer any advantage in promoting
      patency.

PMID- 15467601
TI  - The effect of tonsillectomy and adenoidectomy on inattention and impulsivity as
      measured by the Test of Variables of Attention (TOVA) in children with
      obstructive sleep apnea syndrome.
AB  - OBJECTIVE: To evaluate children with obstructive sleep apnea syndrome (OSAS) for
      features of attention deficit disorder (ADD) using an objective test of
      inattention and impulsivity: Test of Variables of Attention (TOVA) and then to
      determine whether tonsillectomy and adenoidectomy (T+A) results in an improvement
      in TOVA scores. STUDY DESIGN AND SETTING: This study was a prospective
      interventional comparative trial in a tertiary care children's hospital. Nineteen
      children ages 5 to 14 years with OSAS, and otherwise healthy, with a clinical
      indication for T+A. Preoperative and 2 months postoperative OSA-18, CBCL
      questionnaires, and TOVA scores were evaluated. RESULTS: The preoperative TOVA
      scores were in the abnormal range in 12/19 (63%) of the children. The mean
      preoperative TOVA score was -2.9 (+/- 3.1). The mean postoperative TOVA score was
      -0.4 (+/-2.8). The improvement in the TOVA scores was significant ( P < 0.0001, t
      -test). CONCLUSION: This preliminary data suggests that treatment of OSAS with
      T+A results in significant improvement in objective parameters of inattention and
      impulsivity. Significance These findings may be important in understanding the
      impact of OSAS and therapeutic interventions on behavioral problems in children.

PMID- 15467602
TI  - Laser cryptolysis for the treatment of halitosis.
AB  - OBJECTIVE: To evaluate the tonsils as a source of halitosis and to assess the
      efficacy of laser CO(2) cryptolysis for the treatment of oral bad breath caused
      by chronic fetid tonsillitis. METHODS: Fifty-three patients with halitosis
      originating from chronic fetid tonsillitis, who completed laser cryptolysis were
      enrolled in the study. The origin of halitosis was demonstrated by Finkelstein's
      tonsil smelling test, which included massaging the tonsils and smelling the
      squeezed discharge. All patients were treated by laser cryptolysis, an office
      procedure done under topical anesthesia. Subjective and objective postoperative
      assessment was based on self-and-family report and clinical assessment. Patients
      were reexamined 4 to 6 weeks post-treatment, and when the need for further laser
      treatment was determined. RESULTS: Complete elimination of halitosis required one
      session in 28 patients (52.8%), 2 sessions in 18 patients (34%), and 3 sessions
      in 5 patients (9.4%). Follow-up period ranged from 3 to 36 months (mean, 20.8 +/-
      8.5 months). No adverse effects or complications were encountered. CONCLUSIONS:
      After excluding dental or periodontal, sinonasal, oral, pulmonary, or
      gastroenterological diseases as the origin of halitosis, chronic fetid
      tonsillitis remains a common cause of halitosis. Patients suffering from
      halitosis should be treated relying on their examination including Finkelstein's
      tonsil smelling test. Laser CO(2) cryptolysis is an effective, safe, and well
      tolerated procedure for the treatment of halitosis.

PMID- 15467603
TI  - Severe hypertrophy of the base of the tongue in adults.
AB  - The lymphoid follicles at the base of the tongue can be detected when examining
      the pharynx of adults, but the presence of large follicles, denoted "severe"
      hypertrophy of the base of the tongue (HBT) is rare. The objective of the present
      study was to identify severe HBT cases and their symptoms and to correlate them
      with the presence of pharyngolaryngeal signs and esophageal symptoms of
      gastroesophageal reflux (GER) in patients seen at a laryngology clinic. Severe
      HBT was considered to be present when the follicles prevented the view of the
      epiglottis or were massively distributed through the pharynx and larynx. Five
      cases of severe HBT were detected among 306 patients submitted to
      videolaryngoscopy over a period of 2 years, corresponding to 1.6% (5/306) of the
      total sample studied. However, this index markedly increases to 4% (4/101) among
      patients with pharyngolaryngeal signs of GER and reached 7.5% (4/53) among
      patients presenting GER symptoms such as heartburn, regurgitation, retrosternal
      burning feeling, and dysphagia. The complaints due to severe HBT were noisy
      respiration, hoarseness, throat clearing, dry cough, globus pharyngeus, and nasal
      voice. We conclude that the frequency of hypertrophied follicles is increased in
      the presence of signs and symptoms of GER and those HBT symptoms are confused
      with those of GER, except for nasal voice and noisy respiration.

PMID- 15467604
TI  - Safety of outpatient tonsillectomy in children: a review of 6 years in a tertiary
      hospital experience.
AB  - OBJECTIVE: We present our experience with outpatient tonsillectomy in children
      and critically review safety to support the outpatient policy. STUDY DESIGN AND
      SETTING: We conducted a retrospective chart review from January 1995 through
      December 2000 in the pediatric otolaryngology unit of a tertiary care university
      hospital. RESULTS: One thousand two hundred forty-three patients were accepted in
      the outpatient program with permissive criteria. Postoperative observation time
      ranged from 3 to 5 hours (median, 4.5 hours). The overall rate of complications
      was 9.3% (n = 116). Primary and secondary bleeding rates were 6.27% (n = 78) and
      0.48% (n = 6), respectively. Thirty-six children (2.9%) had major bleeding; 2 of
      them were not identified in day-hospital (0.16%). Discharge was delayed in 103
      patients (8.3%), and 13 patients showed complications after discharge (about 1%
      readmission rate). CONCLUSION: Our program outcomes support safety. Outpatient
      surgery is meant to provide comfort to the patient and efficiency to the health
      care system, without impairing safety; in our experience, most tonsillectomies in
      children comply with these objectives. SIGNIFICANCE: Outpatient tonsillectomy in
      children may be safe even with permissive criteria, when an appropriate setting
      is available.

PMID- 15467605
TI  - The importance of etiology on the clinical course of neck abscesses.
AB  - OBJECTIVE: Formation of neck abscesses from injecting illicit drugs continues to
      be a common problem in the United States. We sought to determine whether neck
      abscesses resulting from direct inoculation differ in their clinical course and
      severity from those that arise from direct spread through inflamed tissue, as in
      pharyngitis or odontogenic infections. STUDY DESIGN AND SETTING: Patients were
      separated based on the cause of their neck abscess into either an injection drug
      use group or a noninjection drug use group. We retrospectively compared both
      groups of patients by examining multiple clinical endpoints, including the number
      of operations, length of hospital stay, and requirement for emergent airway
      intervention. RESULTS: Injection drug use was the most common cause of neck
      abscess. Only 1 of these patients needed more than 1 drainage procedure, and no
      patients required emergent airway intervention or an intensive care unit (ICU)
      stay. The majority of the patients in the noninjection drug group had a neck
      abscess as a result of unknown causes; nearly one half required an emergent
      operation for airway management and the mean ICU stay was 2.5 days. CONCLUSION:
      Neck abscesses formed by direct inoculation have a relatively more benign
      clinical course than those resulting from spread through inflamed tissue. The
      latter require a longer hospital stay, more days in the ICU, and more emergent
      intervention.

PMID- 15467606
TI  - An objective assessment of the advantages of retrograde parotidectomy.
AB  - OBJECTIVE: This study was undertaken to determine whether the retrograde
      parotidectomy approach is more efficient than standard anterograde parotidectomy
      without compromise of surgical effectiveness. METHODS: A retrospective analysis
      of patients undergoing parotidectomy was conducted. Cases were divided into those
      undergoing retrograde facial nerve dissection and those undergoing standard
      anterograde facial nerve dissection. From the review of medical records, standard
      demographic information, surgical time, histopathology, estimated blood loss, and
      use of facial nerve monitoring were determined. Pathology was reviewed to
      determine the size of the overall resection specimen as well as the size of the
      lesion excised and margin status. Postoperative complications were also recorded.
      Statistical comparisons were conducted between these 2 approaches for these
      clinical variables such as surgical time, blood loss, tumor margin status and
      relative volume of tissue removed during parotidectomy. RESULTS: 45 patients
      undergoing parotidectomy met inclusion criteria. The average patient age was 50.8
      years with a female preponderance (73%). There were 19 standard parotidectomies
      and 26 retrograde approaches. Compared to standard parotidectomy, retrograde
      parotidectomy consumed less operative time (3.2 versus 1.8 hours, respectively),
      decreased intraoperative blood loss (67.9 cc versus 40.3 cc, respectively), and
      resulted in less removal of normal parotid tissue (volume of normal parotid
      tissue removed in excess of tumor: 23.0 cc versus 6.0 cc, respectively). No
      significant difference in surgical margin status was noted between anterograde
      and retrograde parotidectomy (P = 0.452). CONCLUSIONS: In appropriately selected
      cases, compared with standard anterograde parotidectomy, retrograde parotidectomy
      is more efficient and spares normal parotid tissue without compromising surgical
      margins. Facial nerve monitoring provides a useful adjunct for retrograde
      dissection.

PMID- 15467607
TI  - Harmonic Scalpel versus cold knife dissection in superficial parotidectomy.
AB  - OBJECTIVES: Use of the Harmonic Scalpel has recently been described in thyroid
      surgery, in which it appears to result in decreased operative time and blood loss
      without increasing the incidence of nerve injury when compared to conventional
      techniques of vessel ligation and tissue division. We sought to determine whether
      the use of the Harmonic Scalpel in superficial parotidectomy was associated with
      a difference in operative time, blood loss, or facial nerve injury compared with
      conventional techniques. STUDY DESIGN AND SETTING: The medical records of all
      patients who underwent superficial parotidectomy for benign parotid pathology at
      the Medical College of Georgia and Veterans Affairs Hospital of Augusta, Georgia,
      from 1999 to 2002 were retrospectively reviewed. Patients were excluded if they
      had a history of a bleeding disorder, prior facial nerve weakness, prior parotid
      surgery, malignant pathology, or required total parotidectomy. RESULTS: Forty-two
      patients were eligible for inclusion. Nineteen patients underwent Harmonic
      Scalpel parotidectomy (HS) and 21 patients underwent conventional parotidectomy
      (control group). There were no significant differences between the 2 groups with
      respect to demographic data, pathology, or tumor size. Use of the Harmonic
      Scalpel was associated with a significant reduction in length of surgery (167.5
      +/- 42.6 min vs. 195.5 +/- 37.4 min for controls, P = 0.03) and intraoperative
      blood loss (37.5 +/- 25.8 mL vs. 60.0 +/- 37.1 mL for controls, P = 0.03). There
      were no significant differences between the HS or control groups with respect to
      postoperative drain output (48.7 +/- 33.8 mL vs. 48.0 +/- 22.9 mL, respectively,
      P > 0.05) or facial nerve function. CONCLUSION: Use of the Harmonic Scalpel for
      superficial parotidectomy is safe and may result in reduced operative time and
      blood loss compared with conventional techniques. Significance A safe alternative
      to cold knife superficial parotidectomy is presented with the potential benefits
      of reduced operative time and blood loss demonstrated.

PMID- 15467608
TI  - Salivary epidermal growth factor concentration in adults with reflux laryngitis.
AB  - OBJECTIVE: The mechanisms involved in the mucosal alterations of
      laryngopharyngeal reflux (LPR) have not been well established. Reports indicate a
      decrease in the salivary epidermal growth factor (EGF) of patients with reflux
      esophagitis, but there are no reports of its behavior in LPR. Our objective was
      to determine the salivary concentration of EGF in adults with LPR. STUDY DESIGN
      AND SETTING: Salivary EGF concentration of 26 patients with LPR and 20 healthy
      controls was determined using a commercially available ELISA kit. Patients with
      LPR were graded according to endoscopic and laryngoscopic criteria. RESULTS:
      Salivary EGF concentration was significantly lower in the LPR group when compared
      with controls (P = 0.002). No correlation between the severity of laryngeal
      findings or esophagitis and salivary EGF concentration could be determined.
      CONCLUSIONS: The decreased salivary concentration of EGF in adults with LPR
      suggests that a deficiency in this polypeptide could be associated to the
      disease.

PMID- 15467609
TI  - Parotidectomy for primary nonparotid diseases.
AB  - OBJECTIVE: To analyze the indications and results of parotid gland resections for
      patients with primary nonparotid diseases. STUDY DESIGN AND SETTING:
      Retrospective analysis of 442 consecutive parotidectomies (76 for primary
      nonparotid disease) in a referral head and neck surgery service, tertiary care
      university hospital. RESULTS: Skin cancer (mainly squamous cell and basal cell
      carcinomas) was the most common indication for parotidectomy. Superficial
      parotidectomy with preservation of the facial nerve was the most commonly
      performed operation (61.8%), with some form of nerve sacrifice necessary in
      31.6%. Parotid gland parenchyma and/or lymph nodes were pathologically positive
      in 46 cases. Neck dissections were carried out in conjunction with parotidectomy
      in 42 patients (1 patient had had previous neck dissection), of which 16 turned
      out to be pN+. CONCLUSION: Parotidectomy should be considered as part of the
      surgical treatment of tumors whenever oncologically necessary for appropriate
      margins, lymph node dissection, and for proper identification and preservation of
      the facial nerve.

PMID- 15467610
TI  - Quality of life in hearing-impaired adults: the role of cochlear implants and
      hearing aids.
AB  - OBJECTIVE: To compare the quality-of-life (QOL) benefit received from cochlear
      implants (CIs) and hearing aids (HAs) among hearing-impaired adults. STUDY
      DESIGN: Health-related questionnaire. METHODS: Twenty-seven CI users compared to
      control group of 54 HA users, both older than 49. Questionnaires for the pre
      rehab state (without HA or CI use) and post-rehab state (after HA or CI for 12
      months) were mailed 2 weeks apart. RESULTS: Twenty-six (96.3%) CI and 30 (55.6%)
      HA users responded (P < 0.001, chi-square). Compared to HA patients, CI users
      showed twice as much overall QOL improvement (P = 0.082, multiple linear
      regression) as HA users. Multivariate analysis of variance showed greater QOL
      benefit in CI than HA users across the physical, psychological, and social
      subdomains (P = 0.03). CONCLUSION: Cochlear implants provide at least comparable
      benefit for those with profound hearing loss as hearing aids bring for those with
      less severe hearing loss.

PMID- 15467611
TI  - How do cartilage and other material overlay over a prosthesis affect its
      vibration transmission properties in ossiculoplasty?
AB  - OBJECTIVE: The prosthesis/eardrum interface is often deliberately modified by
      cartilage overlay, or by soft tissue in-growth. We examined the effects of
      vibration transmission to the footplate of inserting cartilage of varying sizes,
      and materials of varying rigidities. STUDY DESIGN AND SETTING: Using fresh human
      cadaveric temporal bones, stapes vibrations were measured. A partial ossicular
      reconstruction prosthesis was covered with differing materials and cartilage
      sizes. Materials used included glass (rigid), cartilage (intermediate), and
      Merocel (soft). Cartilage sizes varied in size relative to the prosthesis head.
      RESULTS: Rigidity of material had little impact. Cartilage size had an impact,
      with smaller cartilage covers performing best. CONCLUSION: Larger cartilage sizes
      performed worse. This could be a result of increased tension on the eardrum from
      larger cartilage size. There is little impact stiffness of interposed material
      stiffness. SIGNIFICANCE: Cartilage of the size used clinically has little impact
      on vibration transmission to the footplate. A wide range of materials could
      clinically be interposed over the prosthesis.

PMID- 15467612
TI  - Revision cochlear implant surgery: causes and outcome.
AB  - OBJECTIVE: To review experience with cochlear implant reimplantations, including
      effect of reinsertion on audiological performance. STUDY DESIGN AND SETTING:
      Retrospective review of cochlear implant reinsertions in patients seen in a
      private tertiary neurotologic practice. Forty-three patients (8 adults and 35
      children) underwent revision cochlear implant surgery for device failure or
      upgrade. Findings at initial and repeat operations were noted, including number
      of electrodes inserted, and speech perception performance data were obtained when
      available. RESULTS: Five complications occurred in the reinsertion operations, 2
      (6%) intraoperative cerebral spinal fluid leaks and 3 (7%) postoperative flap
      breakdowns with implant extrusion. Number of electrodes inserted was unchanged in
      40/43 patients. Speech perception abilities remained stable or improved.
      CONCLUSION: Cochlear reimplantation is technically feasible and allows for
      continued auditory stimulation. SIGNIFICANCE: Patients facing reimplantation must
      be aware of the possibility of differences in sound quality and speech
      recognition performance with their replacement device, but speech perception
      ability will typically remain the same or improve.

PMID- 15467613
TI  - Pediatric temporal bone fractures in a rural population.
AB  - OBJECTIVE: To examine pediatric temporal bone fractures in a rural population.
      STUDY DESIGN AND SETTING: A retrospective chart review of pediatric temporal bone
      fractures between January 1, 1996, and December 31, 2000, at a rural academic
      medical center. RESULTS: A total of 108 patients were identified. Common
      etiologies include falls, bicycle-related injuries, and motor vehicle accidents.
      Animal-related injuries were identified primarily in patients under 5. Facial
      nerve injuries were noted in 7%, hearing loss in 16%, additional skull base
      fractures in 65%, and intracranial injuries in 75%. CONCLUSIONS: Temporal bone
      fracture etiology in the rural pediatric population is associated with age. Young
      children may suffer fractures secondary to animal-related accidents. Patterns of
      injury differ little between rural and urban settings. SIGNIFICANCE: Animal
      related accidents may be a significant cause of temporal bone trauma in rural
      young children. Our data remain unique in that we report additional skull base
      fractures as well as intracranial injuries in this population.

PMID- 15467614
TI  - Diagnostic, pathophysiologic, and therapeutic aspects of benign paroxysmal
      positional vertigo.
AB  - Benign paroxysmal positional vertigo is the most common peripheral vestibular
      disorder. It can be defined as transient vertigo induced by a rapid head position
      change, associated with a characteristic paroxysmal positional nystagmus.
      Canalolithiasis of the posterior semicircular canal is considered the most
      convincing theory of its pathogenesis and the development of appropriate
      therapeutic maneuvers resulted in its effective treatment. However, involvement
      of the horizontal or the anterior canal has been found in a significant rate and
      the recognition and treatment of these variants completed the clinical picture of
      the disease. This paper describes the advances in understanding how this disease
      is generated and discusses the current therapeutic modalities.

PMID- 15467615
TI  - Long-term otological outcome of hamular fracture during palatoplasty.
AB  - OBJECTIVE: It has been suggested that fracture of the hamulus during palatoplasty
      in children with cleft palate may lead to adverse otological sequelae, however,
      there is little evidence to support this. STUDY DESIGN AND SETTING: The
      otological records of 42 children with repaired cleft palate (excluding submucous
      cleft palate) aged 8 years old or older were examined. A questionnaire regarding
      the incidence, treatment, and outcome of middle ear problems was completed by the
      parents of 68 children with repaired cleft palate, aged 9 years old or older.
      RESULTS: There was no significant difference between children who did and did not
      undergo hamular fracture with regard to tympanic membrane appearance, audiometry,
      history of ear problems (P = 1.000), ear infections (P = 0.622), ventilation tube
      insertion (P = 0.532), or surgery for chronic otitis media (P = 1.000). Parents
      of children not undergoing hamular fracture reported a higher incidence of below
      normal hearing (P = 0.023).Conclusion and significance There is no evidence that
      hamular fracture during palatoplasty affects long-term otological outcome in
      cleft palate.

PMID- 15467616
TI  - Incidence of dehiscence of the facial nerve at surgery for middle ear
      cholesteatoma.
AB  - OBJECTIVE: To identify the incidence of dehiscence of the facial nerve in
      patients undergoing surgery for cholesteatoma and to describe its relevance with
      iatrogenic facial nerve injury. STUDY DESIGN AND SETTING: This was a
      retrospective study including 117 tympanoplasties with or without mastoidectomy
      performed in 49 men and 66 women. RESULTS: The presences of FND after
      exenteration of disease are 33.3% of total surgical procedures, 33% of the
      initial procedures, and 37.5% of the revision procedures. The locations of facial
      nerve dehiscence were 87.2% in only the tympanic segment, 7.7% in only the
      vertical segment, and 5.1% in both the tympanic and vertical segments.
      CONCLUSIONS AND SIGNIFICANCE: The incidence of facial nerve dehiscence is high
      (33.3%) in our study. The surgeon should keep in mind that the location of facial
      nerve dehiscence with cholesteatoma is comparable with the most common area of
      iatrogenic facial nerve injury during otologic surgery.

PMID- 15467617
TI  - Anatomic limitations of posterior exposure of the sinus tympani.
AB  - OBJECTIVE: The sinus tympani is a challenging area for the otologic surgeon to
      access and from which to remove the disease process. Recently, a posterior
      approach to the sinus tympani through the mastoid was proposed as an alternative
      technique in cases of deep sinus tympani. STUDY DESIGN AND SETTING: The posterior
      approach was performed by dissecting the triangular bony area formed by the
      facial nerve, lateral semicircular canal, and posterior semicircular canal in 8
      temporal bone specimens. RESULTS: The edges of the triangle on the facial nerve
      and lateral semicircular canal were almost constant at 5 mm. The edge on the
      posterior semicircular canal was about 4 mm. CONCLUSION: It is possible to expose
      the sinus tympani from the posterior by careful dissection through this triangle,
      which has almost constant dimensions.

PMID- 15467618
TI  - Hearing loss in steelband musicians.
AB  - OBJECTIVE: To determine the difference in hearing between a group of steelband
      musicians (pannists) and a control group. DESIGN, SETTINGS, AND SUBJECTS: We
      conducted a controlled cross-sectional pilot study consisting of 29 steelpan
      players and 30 control subjects from a steelpan orchestra (steelband) in the
      Otolaryngology Department of the Eric Williams Medical Sciences Complex. RESULTS:
      Significantly more steelpan players had a hearing loss than the control subjects
      at 3000 Hz, 4000 Hz, and 6000 Hz ( P < 0.01). chi 2 testing for trend
      demonstrated that the longer a steelpan player played his instrument the greater
      the hearing loss. CONCLUSION: These results indicate that pannists suffer
      permanent auditory damage from high-intensity sound levels and that preventative
      measures are required to prevent this hearing loss, particularly in younger
      players.

PMID- 15467619
TI  - A new assay to screen for head and neck squamous cell carcinoma using the tumor
      marker metallopanstimulin.
AB  - OBJECTIVE: To date, no serologic marker has proven effective as a diagnostic test
      for head and neck squamous cell carcinoma (HNSCC). Levels of metallopanstimulin
      (MPS), as measured by a difficult to reproduce radioimmunoassay, are
      significantly elevated in untreated HNSCC patients. Our objective was to develop
      a simpler MPS assay. METHODS: Serum was obtained from HNSCC patients through
      Institutional Review Board approved protocols at the Penn State University
      College of Medicine and healthy volunteers donating blood at the hospital blood
      bank from 2000 to present. Serum MPS was immunoprecipitated, slot blotted, and
      Western blotted. MPS levels were quantified by densitometry. RESULTS: Forty-eight
      blood donors and 45 known HNSCC patients were studied. The MPS level was 14 ng/mL
      +/- 1 (SEM) for blood donors and 36 ng/mL +/- 3 (SEM) for known HNSCC patients.
      The difference was statistically significant (P < 0.0001). CONCLUSION: Slot blot
      analysis of MPS is a safe, effective, and reproducible assay that may be used to
      screen for HNSCC in high-risk populations.

PMID- 15467620
TI  - Multivariate predictors of occult neck metastasis in early oral tongue cancer.
AB  - OBJECTIVES: The elective dissection of cervical lymph nodes from patients with
      early oral tongue cancer and a clinically negative neck (T1/T2N0), remains an
      unsettled issue that continues to be investigated. This study examines clinical
      and histopathologic factors through univariate and multivariate analysis to
      correlate the risk of neck micrometastasis in patients with T1/T2N0 squamous cell
      carcinoma of the oral tongue. STUDY DESIGN AND METHODS: The clinical files and
      histologic sections of tumor from 45 clinically determined N0 patients were
      retrospectively analyzed. The factors examined include degree of tumor cell
      differentiation, T1/T2 staging, presence of perineural invasion, presence of
      angiolymphatic invasion, type of invasion front, depth of muscle invasion, and
      tumor thickness. RESULTS: Independent correlates of positive occult neck
      metastasis included greater tumor thickness ( P = 0.01), greater depth of muscle
      invasion ( P = 0.01), T2 stage ( P = 0.01), poorly differentiated tumors ( P =
      0.007), infiltrating-type invasion front ( P = 0.03), presence of perineural
      invasion ( P = 0.001), and presence of angiolymphatic invasion ( P = 0.005). The
      final multivariate model for estimation of an increased probability of occult
      neck disease included greater tumor thickness, presence of perineural invasion,
      infiltrating-type invasion front, poorly differentiated tumors, and T2 stage.
      CONCLUSIONS: The clinical and histopathologic factors studied herein permit
      greater selectivity and more informed decision-making than does presurgical
      evaluation, when addressing elective neck treatment for early N0 oral tongue
      cancer. The multivariate model derived from this study appears to be a more
      reliable method for determining the patients most likely to benefit from elective
      neck dissection.

PMID- 15467621
TI  - Mutant Nbs1 enhances cisplatin-induced DNA damage and cytotoxicity in head and
      neck cancer.
AB  - OBJECTIVE: Enhanced DNA double-strand break (DSB) repair could be a primary cause
      for development of resistance in tumor cells to cisplatin, which induces
      crosslinks and DNA DSBs. A protein complex consisting of hMre11, hRad50, and Nbs1
      (MRN) has been identified as a critical component in repair of DNA DSBs. The
      present study investigates whether the expression of a truncated form of Nbs1
      interrupts the function of the MRN complex and therefore enhances cisplatin
      induced DNA damage and cytotoxicity in human head and neck squamous cell
      carcinoma (HNSCC). METHODS AND MEASURES: Two human HNSCC cell lines, JHU006 and
      JHU029, were used. A dominant negative recombinant adenovirus expressing domains
      of Nbs1 was constructed. Adenovirus-mediated mutant Nbs1 (Ad-Nbs1) gene transfer
      was performed with replication-defective virus (DL312) and no treatment as
      controls. Transgene expression and cell viability were evaluated in transfected
      cells. Neutral comet assay was performed and the "tail moment," the product of
      the amount of DNA in the tail and the distance of tail migration, was analyzed
      for evaluating DNA DSB damage at 24, 48, and 72 hours. RESULTS: Transgene
      expression of mutant Nbs1 was confirmed by Western blotting. Ad-Nbs1 gene
      transfer significantly increased cisplatin-induced cytotoxicity as shown by
      stunting of 6-day growth curves. Neutral comet analysis revealed that the mean
      tail moment, indicative of DNA damage, was significantly elevated in cells
      treated with combined cisplatin and Ad-Nbs1 compared to cisplatin alone in both
      cell lines. CONCLUSIONS: Expression of mutant Nbs1 significantly increases
      cisplatin-induced DNA DSBs and cytotoxicity. The increase in double-strand DNA
      damage corresponds to the level of cytotoxicity in the different treatment groups
      and suggests that tumor chemosensitization occurs through augmentation of DNA
      DSBs. CLINICAL SIGNIFICANCE: Alteration of DNA repair may provide a novel
      approach to enhancing sensitivity of HNSCC to chemotherapy. Our study supports
      the potential application of Ad-Nbs1 in combination with cisplatin for treatment
      of advanced and metastatic HNSCC.

PMID- 15467622
TI  - Efficacy of routine bilateral neck dissection in the management of supraglottic
      cancer.
AB  - OBJECTIVE: In a previous study, we reported that the contralateral undissected
      neck was the most common site of failure in patients treated for squamous cell
      carcinoma of the supraglottic larynx. Since then, we have altered our treatment
      of all patients with T2-T4 supraglottic cancer and selective T1 cases to include
      routine bilateral neck dissection. In the present study, we compare the long-term
      efficacy of routine bilateral neck dissections to historic controls in the
      treatment of patients with supraglottic cancer. STUDY DESIGN AND SETTING: A
      retrospective chart review on all patients undergoing primary surgery for
      supraglottic carcinoma between 1989 and 2000 was performed. All had undergone
      routine bilateral neck dissection. The most proximal area of recurrent disease
      was identified as the site of recurrence. Rates of recurrence, 2-year overall
      survival, and 2-year disease-specific survival were calculated. Results were
      compared to historical data using Fisher's exact test. RESULTS: Of 180 patients
      identified, 115 patients with minimum 2-year follow-up and meeting exclusion
      criteria were included in the analysis. Four patients (3.5%) experienced local
      recurrence, 9 patients (7.8%) had cervical recurrence, and 8 patients had distant
      spread (7.0%). Recurrence in the neck (7.8%) has been significantly reduced from
      the historical recurrence rate (20%) prior to instituting routine bilateral neck
      dissections ( P = 0.009). The 2-year survival increased from 72% to 82.6% ( P =
      0.0408). CONCLUSION AND SIGNIFICANCE: Routine bilateral neck dissection decreases
      cervical recurrence and appears to improve survival in the management of
      supraglottic cancer.

PMID- 15467623
TI  - Is the delay in starting postoperative radiotherapy a key factor in the outcome
      of advanced (T3 and T4) laryngeal cancer?
AB  - OBJECTIVE: To identify factors influencing the outcome of postoperative
      radiotherapy in patients with advanced laryngeal cancer. DESIGN: The files of 44
      patients with advanced laryngeal cancer who were treated by surgery followed by
      radiotherapy (24 with pT3 and 20 with pT4) were reviewed. Median delay in
      starting radiotherapy was 50 days (range, 19-150 days). Treatment variables, in
      addition to certain patient and tumor characteristics, were analyzed in terms of
      locoregional control and survival. SETTING: Major referral tertiary center in
      central Israel. RESULTS: Locoregional control rates were 86% and 81% at 2 and 5
      years, respectively, and corresponding survival rates were 82% for both. Only
      nodal involvement retained statistical significance for both locoregional control
      as well as survival on multivariate analysis (P = 0.0009 and P = 0.0004,
      respectively). CONCLUSIONS: This is the first study showing that delay in
      postoperative radiotherapy in advanced laryngeal cancer is not a significant
      predictor of locoregional control or survival in advanced laryngeal cancer. Only
      lymphatic spread was found to have a significant influence on treatment outcome.

PMID- 15467624
TI  - Status of internal jugular veins in patients with carcinomas of the head and neck
      area.
AB  - OBJECTIVE: To assess the status of internal jugular veins (IJV) in patients with
      head and neck carcinomas. STUDY DESIGN AND SETTING: This study included 108 IJV
      of 54 cancer patients who were prospectively evaluated between September 1994 and
      February 1997. Patency, presence of thrombosis, characteristics of vein wall,
      compressibility, area of the veins both in rest and during Valsalva maneuver,
      expiratory flow speed, Valsalva flow speed, jugular flow in each side, and total
      jugular flow were registered in all cases. Also, 30 IJV of 15 normal volunteers
      were used as a control group. The study was performed in a tertiary care referral
      center. RESULTS: Right expiratory flow speed was higher in volunteers (P =
      0.0280), and left basal area was bigger in oncologic patients (P = 0.0394). No
      significant changes were found between cancer patients and controls in the
      remaining parameters (P > 0.05). CONCLUSIONS AND SIGNIFICANCE: According to these
      results, head and neck carcinomas do not seem to affect the ultrasonographic
      characteristics of IJV. Thus, preoperative evaluation of IJV is not mandatory in
      these patients.

PMID- 15467625
TI  - Salvage surgery for locally recurrent nasopharyngeal carcinoma-A 10-year
      experience.
AB  - OBJECTIVE: To evaluate the result of salvage surgery for patients with primary
      recurrence of nasopharyngeal carcinoma (NPC) after radiation therapy. STUDY
      DESIGN AND SETTING: Prospective cohort at a tertiary referral center. PATIENTS
      AND METHODS: Thirty-eight consecutive patients with primary recurrence of NPC
      after radiation failure underwent salvage surgery for curative intention via the
      facial translocation approach from July 1993 to December 2002. The follow-up time
      ranged from 2 to 88 months. Twelve patients with intracranial and skull base
      invasion needed a combined neurosurgical approach. Eight patients had additional
      postoperative radiation therapy. RESULTS: The actuarial 3-year survival and local
      control rate was 60% and 72.8%, respectively. Ten (83.3%) of 12 patients with
      intracranial and skull base invasion achieved local control. There was no
      surgical mortality, and the morbidity rate was only 13.2%. CONCLUSION AND
      SIGNIFICANCE: The results of this study reveal better outcome of salvage surgery
      than that of most published literature of reirradiation for recurrent NPC. With
      the adequate exposure provided by the facial translocation approach, an
      integrated concept of skull base surgery, and the collaboration of neurosurgeons,
      we can extend our surgical indications of salvage surgery and resect many
      advanced lesions with acceptable mortality and morbidity.

PMID- 15467626
TI  - Functional surgical approach to the level I for staging early carcinoma of the
      lower lip.
AB  - OBJECTIVE: The management of the neck in patients with T1-T2 carcinoma of the
      lower lip (LLC) remains controversial. Suprahyoid neck dissection seems a
      reliable diagnostic approach, although it sacrifices the submandibular gland and
      its vascularity. STUDY DESIGN AND SETTING: This study was a prospective,
      randomized study. Patients with previously untreated T1 or T2 primary LLC
      underwent either classical suprahyoid neck dissection (CSHD) or functional
      suprahyoid neck dissection (FSHD) in continuity with the resection of the cancer
      of the lip. RESULTS: A total of 48 suprahyoid neck dissections were performed in
      36 patients. Among these dissections, 27 were CSHD and 21 were FSHD. The average
      number of dissected lymph nodes was similar for both classical and functional
      type operations. The overall follow-up period was 40.5 months. CONCLUSIONS: The
      end result of this series supports the idea that FSHD is a reliable diagnostic
      method for the management of level I lymph nodes in LLC. FSHD can avoid
      undertreatment or overtreatment of the patients with early LLC while preserving
      the submandibular gland.

PMID- 15467627
TI  - Cyclin D1, p53, MIB1, intratumoral microvessel density, and human papillomavirus
      in advanced laryngeal carcinoma: association with nodal metastasis.
AB  - OBJECTIVE: We sought to study various parameters in laryngeal squamous cell
      carcinoma (LSCC) that might predict nodal metastasis. STUDY DESIGN AND SETTING:
      Sixty-four LSCCs were examined with respect to their histopathology and, using
      immunohistochemistry, their proliferative capacity (MIB1), p53 and cyclin D1
      status, and intratumoral microvessel density. The presence of human
      papillomavirus was ascertained by the polymerase chain reaction. RESULTS:
      Histopathologically, most tumors had an infiltrating/mixed growth pattern and a
      diminished inflammatory reaction at the growing margin. In addition, 56% of the
      tumors were positive for MIB1, with 64% showing p53 overexpression; 70% were
      positive for cyclin D1; and 59% showed increased tumor microvessel density. Of 42
      cases analyzed, 9.5% were positive for human papillomavirus 16. CONCLUSIONS: Of
      the parameters studied, a diminished lymphocytic inflammatory response at the
      periphery (P < 0.05) and cyclin D1 overexpression (P < 0.001) correlated
      significantly with cervical nodal metastasis at presentation. SIGNIFICANCE:
      Cyclin D1 overexpression, easily assessed on biopsy samples, may thus help in
      optimizing therapy at the outset.

PMID- 15467628
TI  - Factors associated with failure of frontal sinusotomy in the early follow-up
      period.
AB  - OBJECTIVES: To understand factors associated with failure of endoscopic frontal
      sinusotomy. METHODS: Retrospective review of 130 consecutive frontal
      sinusotomies. The preoperative extent of disease was graded radiologically in
      each frontal sinus as total opacification, partial opacification, or mucosal
      thickening. Records were also reviewed to determine the incidence of comorbid
      conditions. RESULTS: Patency at most recent follow-up was observed in 117/130
      (90%). Patency was achieved after our first procedure in 107 sinusotomies. These
      were considered successes. Ten required revision surgery, and an additional 13
      were not patent at last follow-up. These 23 sinusotomies were considered
      failures. Among those failing our initial surgery, 19/23 (83%) were partially or
      totally opacified preoperatively. In contrast, only 47/107 (44%) in the success
      group contained partial or total opacification preoperatively (P = 0.003), with
      the majority exhibiting mucosal thickening only. Mean follow-up was 8.3 months
      for the successes and 10.7 months for the failures (P = NS). No significant
      differences were observed between the success and failure groups with respect to
      the prevalence of asthma, aspirin sensitivity, or allergic fungal disease.
      Patients in the failure group, however, had a higher mean number of prior
      surgeries before undergoing frontal sinusotomy at our institution (1.8 vs 0.9, P
      = 0.033). CONCLUSIONS: During the early follow-up period, failure of endoscopic
      frontal sinusotomy is associated with advanced degrees of preoperative disease
      within the sinus and is also more likely in patients who have failed prior
      surgical management.

PMID- 15467629
TI  - A simplified technique for airway correction at the nasal valve area.
AB  - OBJECTIVE: To describe a simplified system to correct an obstructed nasal airway
      utilizing the Mitek bone anchor suspension technique (BAST). STUDY DESIGN: This
      is a retrospective/prospective study of patients with nasal airway obstruction
      treated with the BAST. The retrospective study is based on 188 patients who
      underwent the BAST over the past 5 years and were analyzed to assess
      complications and subjective results. The prospective group consisted of 52
      patients with unilateral or bilateral valve obstruction who were assessed with
      preoperative and postoperative rhinomanometry and quality of life (QOL)
      questionnaires. METHODS: The surgical technique is based on introducing a bone
      anchor into the orbital rim through a 4-mm stab incision. The bone anchor system
      comes with attached sutures that are easily passed to the valve area and secured
      in position to support and open the valve area. Preoperative and postoperative
      QOL surveys and rhinometric studies were compared in 52 patients to assess the
      subjective and objective outcomes of the procedure. RESULTS: Based on subjective
      data, over 90% of the patients had significant improvement in their nasal airway.
      Objectively, cross-sectional areas at the nasal valve were found to have
      significantly improved postoperatively (P < 0.046). Complications were rare and
      limited to localized infection, reaction to sutures, and loss of support.
      CONCLUSION: Correction of nasal valve obstruction with this technique provides a
      simplified alternative in selected patients to improve airflow and decrease nasal
      resistance. The BAST allows for a simple, highly effective correction of an
      obstructed airway with minimal complications.

PMID- 15467630
TI  - The role of agger nasi air cells in patients requiring revision endoscopic
      frontal sinus surgery.
AB  - OBJECTIVES: To determine the association of agger nasi air cell disease with
      frontal rhinosinusitis, assessed by computed tomography (CT), in patients who
      require revision functional endoscopic sinus surgery (FESS). METHODS: We
      prospectively collected data on patients undergoing revision FESS at a tertiary
      care medical center over an 18-month period. Sinus CT scans were graded as per
      Lund-Mackay. Frontal sinus findings on CT scan were correlated with the presence
      or absence of disease in agger nasi air cells. RESULTS: Eighty patients underwent
      revision FESS in an 18-month period. A total of 160 sides were evaluated by sinus
      CT scan with agger nasi being present in all but 11 sides (93%). One patient did
      not have a pneumatized frontal sinus on 1 side and so 148 sides were available
      for study. Frontal sinus disease was present in 119 and absent in 29 sides. The
      average CT grade of patients with frontal rhinosinusitis was 8.4 while it was
      only 3.0 in patients without frontal rhinosinusitis (P = 0.000). Agger nasi air
      cell disease was present in only 3 of 29 (10%) sides in patients without frontal
      rhinosinusitis and was present in all 119 (100%) sides of patients with frontal
      rhinosinusitis (P = 0.0000). CONCLUSION: Agger nasi air cells are a common
      anatomic feature, present in 93% of our patients. Agger nasi air cell disease
      correlates strongly with frontal sinus disease as assessed by sinus CT scan in
      patients undergoing revision FESS. In addition, frontal sinus disease correlates
      with the severity of overall sinus disease as determined by sinus CT scan.

PMID- 15467631
TI  - The effect of maxillary sinus antrostomy size on xenon ventilation in the sheep
      model.
AB  - OBJECTIVE: A major goal of maxillary antrostomy is to increase sinus ventilation.
      Limited data exist regarding the effect of maxillary antrostomy size on sinus
      ventilation. We sought to quantify the effect of uncinectomy, small antrostomy,
      and large antrostomy on maxillary sinus ventilation using xenon-enhanced CT in
      the sheep model. MATERIALS, STUDY DESIGN, AND METHODS: A xenon-oxygen-air mixture
      was delivered to 8 fresh cadaveric sheep heads while repeated CT scans were
      performed through the maxillary sinuses. Baseline and postoperative studies were
      performed after an endoscopic uncinectomy, small antrostomy, or large antrostomy
      was created. Images were analyzed to measure the density of the xenon gas in the
      maxillary sinus as a function of time, generating a time constant. RESULTS: The
      time constants for both small antrostomy and large antrostomy were significantly
      different compared to baseline ( P = 0.003 for both). The time constant
      comparison between small antrostomy and large antrostomy was not significant ( P
      = 0.948). CONCLUSIONS: A small antrostomy produces a statistically significant
      increase in maxillary sinus ventilation over baseline. No significant further
      ventilation increase is obtained by creating a large antrostomy in the sheep
      model. This lends credence to the use of small antrostomies to improve maxillary
      sinus ventilation in human sinus surgery.

PMID- 15467632
TI  - Chronic panrhinosinusitis without nasal polyps: long-term outcome after
      functional endoscopic sinus surgery.
AB  - OBJECTIVE: The goal of this study was to evaluate the long-term outcome after
      functional endoscopic sinus surgery (FESS) for chronic panrhinosinusitis without
      nasal polyps by using symptom scoring and an endoscopic outcome evaluation. STUDY
      DESIGN: Seventy-seven patients with chronic panrhinosinusitis without nasal
      polyps (Kennedy computed tomography [CT] scan stages I to III) were followed up
      for at least 3 years after FESS. Preoperative evaluation included a CT scan and
      an immunoallergologic evaluation. Three years after FESS, all patients were
      interviewed and scored endoscopically. RESULTS: Ninety-two percent of the
      patients showed a marked global improvement after FESS. The endoscopic control
      showed normal findings in 54% of all ethmoidal cavities. The postoperative
      endoscopic score correlated significantly with the subjective satisfaction
      ratings (P < 0.001). The preoperative CT staging proposed by Kennedy was
      predictive for necessity of revision surgery in 15% of the patients. CONCLUSIONS:
      Our data suggest that FESS for chronic panrhinosinusitis without nasal polyps has
      a good long-term outcome on subjective symptoms and endoscopic findings.
      SIGNIFICANCE: According to this study, subjective improvement correlates
      significantly with the postoperative endoscopic findings in the ethmoidal
      cavities of patients with chronic panrhinosinusitis without polyps at a long-term
      follow-up.

PMID- 15467633
TI  - Small and large middle meatus antrostomies in the treatment of chronic maxillary
      sinusitis.
AB  - OBJECTIVE: The study goal was to compare the postoperative endoscopic appearance
      of the middle meatus antrostomy with symptomatic relief in patients undergoing
      endoscopic endonasal sinus surgery for chronic maxillary sinusitis. STUDY DESIGN:
      We conducted a prospective randomized study encompassing 133 patients with
      chronic rhinogenic maxillary sinusitis who underwent endoscopic ethmoid surgery
      and middle meatal antrostomies. One of the tasks was to compare small-sized (less
      than 6 mm) antrostomies with large-sized (more than 16 mm) antrostomies in
      relieving the symptoms of chronic maxillary sinusitis. During follow-up an
      attempt was made to correlate endoscopic findings with symptomatic failure.
      RESULTS: We could not demonstrate a statistically significant correlation between
      the degree of improvement of the main sinusitis symptoms (obstruction, headache,
      and nasal discharge) and the postoperative size of the antrostomy. Nevertheless,
      persistent accessory maxillary ostia, scarring within the ethmoid were
      statistically significant predictors of poor surgical outcome. CONCLUSION: We
      conclude from this study that the size of the middle meatal antrostomy has no
      influence on the outcome of endonasal surgery for chronic rhinogenic maxillary
      sinusitis.

PMID- 15467634
TI  - Surface electromyographic studies of swallowing in normal subjects: a review of
      440 adults. Report 1. Quantitative data: timing measures.
AB  - OBJECTIVE: Surface electromyographic studies were performed on 440 normal adults
      to establish normative database for duration of muscle activity during swallowing
      and drinking clinically useful for outpatient ENT department. STUDY DESIGN:
      Prospective observational study of healthy volunteers. METHODS: Parameters
      evaluated during swallowing include the timing of activity of the orbicularis
      oris, masseter, submental, and infrahyoid muscle groups covered by platisma. Five
      tests were examined including voluntary single swallows of saliva ("dry"
      swallow), voluntary single water swallows as normal, voluntary single swallows of
      excessive amount of water (20 mL), continuous drinking of 100 mL of water
      (duration and number of swallows), monitoring of spontaneous swallowing of saliva
      during 1 hour period. The duration of oral, pharyngeal, and initial esophageal
      stages of swallowing (mean + SD) were measured for groups of adults of different
      age (18-30, 31-40, 41-50, 51-60, 61-70, 70+ years old). RESULTS: Normative data
      for duration of muscle activity during single swallowing and continuous drinking
      are established for healthy adults. The duration of swallows and drinking in all
      tests showed insignificant increase with the age except for the geriatric group,
      in which this tendency is statistically significant (1-dimensional analysis of
      variance, SPSS, Chi-square criterion, 95% confidence interval). There was no
      statistically significant difference between male and female adults duration of
      muscle activity during single swallowing and continuous drinking in all age
      groups (P >/= 0.05). The relevance and clinical utility of new and alternative
      measures, in particular, are discussed. CONCLUSION: Surface EMG of swallowing is
      a simple and reliable noninvasive method for screening evaluation of swallowing
      with low level of discomfort during the examination. Stage-by-stage evaluation of
      duration can be very important for topical diagnosis of etiology of dysphagia.
      The normative timing of events data can be used for evaluation of complaints and
      symptoms, as well as for comparison purposes in preoperative and postoperative
      stages and in EMG monitoring during ENT treatment. These parameters represent
      stages required for normal deglutition, and can be used to identify abnormalities
      in ENT patients, and provide a basis for comparison of swallowing performance
      both within and between patients.

PMID- 15467635
TI  - Mononeuropathy of the laryngeal recurrent nerve as possible manifestation of
      human immunodeficiency virus infection.

PMID- 15467636
TI  - Lingual abscess: secondary to follicular tonsillitis.

PMID- 15467637
TI  - Dural arteriovenous fistula and tinnitus: case report.

PMID- 15467639
TI  - Back to basics.

PMID- 15467640
TI  - Initiatives for credentialing CAM practitioners.

PMID- 15467641
TI  - Assessing the impact of the ADA.

PMID- 15467643
TI  - Finding the common elements in our practices.

PMID- 15467644
TI  - Alzheimer's disease: an overview.

PMID- 15467645
TI  - Assessing and interviewing patients for meaningful behavioral change: Part 1.

PMID- 15467646
TI  - Was that fee or free? Managing communication barriers.

PMID- 15467647
TI  - Building a trend kit for the future.

PMID- 15467648
TI  - Evidence-based practice as a tool for case management.

PMID- 15467654
TI  - Presidential address: Surgical leadership--lessons learned.

PMID- 15467655
TI  - Laparoscopic sigmoid colectomy after acute diverticulitis: when to operate?
AB  - BACKGROUND: Laparoscopic sigmoid colectomy has become an acceptable method of
      surgical treatment for diverticulitis. However, an optimal waiting period before
      attempting elective laparoscopic colectomy has not been established. We sought to
      evaluate the relationship between the time interval from an acute episode of
      diverticulitis to laparoscopic colectomy and surgical outcomes. METHODS: All
      patients undergoing laparoscopic colectomy during a period of 10 years in a
      single institution were studied. Retrospectively collected data included patient
      demographics, American Society of Anesthesiologists score, prior episodes of
      diverticulitis, interval between last attack and operation, operative time,
      complications, conversion, and recovery period. RESULTS: A total of 120 patients
      were included; 89 had a primary diagnosis of diverticulitis. Mean interval from
      acute diverticulitis to operation was 64 days (range, 1 to 240). Median number of
      episodes of diverticulitis before colectomy was 3 (range, 1 to 10). Ten patients
      (11%) required conversion from laparoscopic to open colectomy. Neither interval
      from acute attack to operation nor number of prior episodes of diverticulitis was
      associated with any significantly increased rate of conversion to open colectomy,
      complication rate, operative time, or recovery period (P=not significant).
      CONCLUSIONS: Our study showed no direct relationship between surgical timing
      after acute diverticulitis and complication or conversion rates after elective
      laparoscopic sigmoid colectomy.

PMID- 15467656
TI  - Unsatisfactory weight loss after vertical banded gastroplasty: is conversion to
      Roux-en-Y gastric bypass successful?
AB  - BACKGROUND: In 1991, the National Institutes of Health sanctioned 2 operations
      for treatment of morbid obesity: vertical banded gastroplasty (VBG) and Roux-en-Y
      gastric bypass (RYGB). Long-term results with VBG are disappointing. We wondered
      whether patients who had "adapted" to the VBG anatomy and had regained weight
      would lose weight after conversion to RYGB. METHODS: We reviewed data on patients
      undergoing conversion of VBG to RGYB. RESULTS: Fifty-four patients (mean body
      mass index [BMI] of 46 kg/m2 [range, 36-66]) underwent standard (48 patients) or
      distal (malabsorptive) (6 patients) RYGB. There were no perioperative deaths;
      postoperative morbidity delaying discharge occurred in 7 patients (13%). Follow
      up (complete in 51 patients, x=6.1 years) was obtained by mail questionnaires and
      patient contact. Mean BMI decreased to 35 kg/m 2 (range, 22-47), and 59% of the
      patients with >1 year follow-up had a BMI <35 kg/m2 . The number of patients
      requiring positive pressure oxygen for sleep apnea decreased by half; most
      patients discontinued or decreased the number of medications treating weight
      related comorbidities. At last follow-up, 90% of patients were satisfied
      subjectively with the results. CONCLUSIONS: Conversion of VBG to RYGB is safe and
      provides weight loss, improved quality of life, and reversal of weight related
      comorbidities.

PMID- 15467657
TI  - Perioperative antibiotic prophylaxis in the gastric bypass patient: do we achieve
      therapeutic levels?
AB  - BACKGROUND: Perioperative surgical antibiotic prophylaxis requires that
      therapeutically effective drug concentrations be present in the tissues. METHODS:
      Patients undergoing Roux-en-Y gastric bypass for morbid obesity were given 2 g
      cefazolin preoperatively, followed by a second dose at 3 hours. Thirty-eight
      patients were each assigned to 1 of 3 body mass index (BMI) groups: (A) BMI=40-49
      (N = 17); (B) BMI=50-59 (N=11); (C) BMI > or= 60 (N=10). Multiple timed serum
      (baseline; incision, 15, 30, 60 minutes; prior to second prophylactic dose; and
      closure) and tissue (skin, subcutaneous fat, and omentum) specimens were
      collected and cefazolin concentration analyzed by microbiological assay. RESULTS:
      No significant difference was observed in intraoperative fluid replacement or
      blood loss among BMI groups. Serum antimicrobial concentrations exceeded
      resistance breakpoint (32 microg/mL) in 73%, 68%, and 52% of BMI groups A, B, and
      C, respectively. No significant difference in cefazolin concentration was
      observed in mean incisional skin and closure tissue specimens in groups A, B, and
      C. A significant decrease in cefazolin concentration was noted in closure adipose
      (p=.04), initial (p=.03) and closure omentum (p=.05) tissues in groups B and C
      compared with A. Over 90% of serum samples exhibited therapeutic concentrations
      covering 53.8% of gram-positive and 78.6% of gram-negative surgical pathogens.
      However, therapeutic tissue levels were achieved in only 48.1%, 28.6%, and 10.2%
      of groups A, B, and C, respectively. CONCLUSIONS: Pharmacokinetic analysis
      suggests that present dosing strategies may fail to provide adequate
      perioperative prophylaxis in gastric bypass patients.

PMID- 15467658
TI  - Endovascular aortic repair or minimal incision aortic surgery: Which procedure to
      choose for treatment of high-risk aneurysms?
AB  - BACKGROUND: This study evaluates use of endovascular aortic repair (EVAR) and
      minimal incision aortic surgery (MIAS) for treatment of high-risk patients with
      infrarenal aneurysms. METHODS: A retrospective review of patients treated with
      EVAR or MIAS between 2000 and 2002 was performed. High-risk criteria included age
      older than 80 years, creatinine level greater than 3.0 mg/dL, recent myocardial
      infarction, congestive heart failure, severe chronic obstructive pulmonary
      disease, hostile abdomen, or morbid obesity (body mass index greater than 30).
      Patient demographics, duration of stay, morbidity, and mortality were compared.
      Exclusionary criteria for EVAR treatment included neck less than 1.5 cm or
      greater than 26 mm in diameter, densely calcified iliac arteries less than 6 mm,
      or creatinine level greater than 3.0 mg/dL. Exclusionary criteria for MIAS
      included pararenal abdominal aortic aneurysm, aneurysm greater than 10 cm, and
      morbid obesity. RESULTS: Eighty-four patients were treated (61 EVAR, 23 MIAS).
      Average age for EVAR was 74 years and 72 years for MIAS. Average aneurysm size
      was 6 cm for both. American Society of Anesthesiologists score was 3.1 for EVAR
      and 3.0 for MIAS patients. Thirty-two of 61 EVAR patients (52%) had 2 risk
      factors, and 12 of 61 (20%) had 3 risk factors. Seven of 23 MIAS patients (30%)
      had 2 risk factors, and 7 had more than 3 risk factors (30%). There were 2 EVAR
      deaths (3%) from multiorgan failure and 1 MIAS death (4%) from myocardial
      infarction. Average duration of stay was 5.1 days for both EVAR and MIAS. Thirty
      day morbidity was 18% for EVAR and 17% for MIAS patients. CONCLUSIONS: EVAR and
      MIAS are comparable for the treatment of high-risk aneurysm patients.

PMID- 15467659
TI  - Campath-1H in renal transplantation: The University of Wisconsin experience.
AB  - BACKGROUND: Immune cell depletion is known to prevent renal allograft rejection
      and injury. We evaluated the humanized monoclonal antibody Campath-1H
      (alemtuzumab; ILEX Oncology, San Antonio, Texas) in renal transplant recipients
      for its safety and efficacy in preventing rejection when used in combination with
      a calcineurin inhibitor, mycophenolate mofetil, and low-dose steroid therapy.
      METHODS: One hundred twenty-six consecutive renal allograft recipients received 2
      doses of Campath-1H antibody on days 0 and 1. Outcomes were compared to patients
      who received an anti-CD25 antibody (n=799), Thymoglobulin (n=160), or other
      antibody treatment (n=156) in combination with a calcineurin inhibitor,
      mycophenolate mofetil, and higher dose steroids. RESULTS: The Campath-1H group
      overall experienced less rejection than the other 3 groups (P=.037). Patients
      with delayed graft function experienced less rejection with Campath-1H than
      control groups (P=.0096) and improved graft survival (P=.0119). There was no
      difference in infection or malignancies between the 4 groups. CONCLUSIONS:
      Campath-1H was well tolerated in renal transplant patients and led to significant
      reductions in incidence of rejection. Patients with delayed graft function
      experienced significantly improved graft survival.

PMID- 15467660
TI  - Continuous local anesthetic infusion for pain management after outpatient
      inguinal herniorrhaphy.
AB  - BACKGROUND: The purpose of the present study is to compare postoperative pain and
      functional outcomes in patients undergoing inguinal herniorrhaphy who receive a
      continuous wound infusion of bupivacaine to those who receive an infusion of
      saline. METHODS: A prospective, randomized, blinded, placebo-controlled trial was
      conducted in adults undergoing outpatient inguinal herniorrhaphy. Patients
      received saline or bupivacaine through a disposable infusion pump for 60 hours
      postoperatively. Pain outcomes were assessed, as were functional outcomes
      (activity, return of bowel function) and side effects. RESULTS: On postoperative
      day 1, patients who received bupivacaine had lower ratings for worst pain than
      patients who received saline, (5.0 +/- 2.3 vs 6.7 +/- 2.2, P=.002). On day 1,
      least pain ratings were also lower, and patients ambulated more frequently than
      those who received placebo. There were no differences between groups from
      postoperative days 2 to 5. There were no differences between groups in the amount
      of hydrocodone consumption. CONCLUSIONS: Continuous infusion of local anesthetic
      after inguinal herniorrhaphy provides modest improvements in pain scores and
      functional outcomes when compared with placebo. However, these effects are
      limited to the first postoperative day only. The additional costs associated with
      this intervention may limit its widespread use in clinical practice.

PMID- 15467661
TI  - Long-term follow up and prognostic factors for cryotherapy of malignant liver
      tumors.
AB  - BACKGROUND: The aims of this study were to determine the long-term outcomes of
      cryotherapy in patients with hepatic malignancies and to describe prognostic
      factors that may affect survival. METHODS: Ninety-eight patients (56 colorectal
      metastases, 28 noncolorectal metastases, 14 hepatocellular carcinomas) undergoing
      hepatic cryosurgery were identified in a retrospective review from January 1994
      to December 2002. RESULTS: Overall survival rates at 1-, 2-, 3-, and 5- years
      were 81%, 62%, 48%, and 28%, respectively(median survival, 33 months) compared to
      a hepatic recurrence-free survival of 76%, 42%, 24%, and 16%, respectively
      (median hepatic recurrence-free survival, 20 months). Median follow-up was 54
      months. Three hundred lesions were cryoablated; the recurrence per cryolesion was
      5%. Major complications were the lone factor that significantly reduced overall
      (P=.0005) and hepatic recurrence-free survival (P=.0005). The number of lesions
      (TNL) and total estimated area (TEA) cryoablated did not significantly affect
      overall or hepatic recurrence-free survival. Additionally, outcomes depending on
      tumor type were not significantly different. CONCLUSIONS: Cryotherapy is an
      important option for a wide range of unresectable malignant hepatic tumors and
      provides the potential for long-term survival. Patients with major complications
      at the time of cryotherapy suffer a decreased overall and hepatic recurrence-free
      survival.

PMID- 15467662
TI  - The association of bloody nipple discharge with breast pathology.
AB  - BACKGROUND: It is believed that bloody spontaneous nipple discharge (SND)
      portends a greater chance of malignancy than nonbloody discharge, and that
      cytologic evaluation of SND assists in treatment planning. Our aims were to
      assess (1) the pathology of women with/without SND who require diagnostic breast
      surgery, (2) whether bloody SND is associated with a different spectrum of
      pathologic findings than nonbloody, and (3) whether SND cytology is influenced by
      pathologic findings. METHODS: One hundred seventy-five women who underwent breast
      operation were enrolled. Cytologic evaluation was performed on Papanicolaou
      stained cytospin preparations of SND. RESULTS: Papilloma and hyperplasia (both
      without atypia) were more frequent in breasts with than without SND; breast
      cancer was more common in breasts without SND (P <.001 for all). All cases of
      breast cancer with SND, but only 33% without, contained a papilloma or papillary
      features. Seventy-five percent of cancers presenting with SND were nonbloody.
      Papilloma was the most common diagnosis in breasts with bloody SND and was more
      common (P=.017) than in breasts without, whereas hyperplasia was the most common
      diagnosis in breasts with nonbloody SND and was more common (P=.031) than in
      breasts with bloody SND. SND cytology was not significantly influenced by
      pathology. CONCLUSIONS: Breast cancer can present as unilateral nonbloody SND,
      indicating the importance of surgical intervention. Papilloma was more common in
      women with SND than without and most often presented as bloody SND.

PMID- 15467663
TI  - Delivery of radiofrequency energy to the lower esophageal sphincter improves
      symptoms of gastroesophageal reflux.
AB  - BACKGROUND: The Stretta procedure has been proposed as a novel therapeutic
      alternative to antireflux surgery for gastroesophageal reflux disease (GERD).
      Early reports indicated improvement in GERD symptoms overall, but improvement in
      patients who have poor outcome after surgery remains unclear. METHODS: Patients
      with reflux who did not have a hiatal hernia were offered the procedure. All were
      administered a GERD Health Related Quality of Life survey at preprocedure and at
      greater than 3 months postprocedure. Differences in pre- and postprocedure
      responses were deemed significant with the use of the Wilcoxon rank sum test with
      P <.05. RESULTS: Fifty patients underwent the Stretta procedure. There were no
      complications. All were evaluated postprocedure, with 74% completing a
      postprocedure survey. Overall heartburn score improved from 3.19 (scale, 0-5)
      preprocedure to 1.74 postprocedure (P=.0012). Overall symptoms satisfaction score
      improved from 3.92 to 1.63 (P=.0001). Symptoms satisfaction score of patients who
      failed antireflux surgery improved from 3.5 to 1.75 (P=.0166), and, in those with
      a body mass index >30, it improved from 4.11 to 1.56 (P=.0024). Four patients
      went on to have antireflux surgery after having the Stretta procedure.
      CONCLUSIONS: Stretta improves heartburn symptoms both overall and in patients
      with poor outcome after antireflux surgery, with a low procedural risk. It may
      have a role in the treatment of patients with primary reflux and in those who
      have failed antireflux surgery or who are a high risk for surgery.

PMID- 15467664
TI  - Fertility is reduced after restorative proctocolectomy with ileal pouch anal
      anastomosis: a study of 300 patients.
AB  - BACKGROUND: Restorative proctocolectomy and ileal pouch anal anastomosis
      (RP/IPAA) has become the gold standard surgical therapy for the majority of
      patients with mucosal ulcerative colitis and familial adenomatous polyposis. The
      aims of this study were to evaluate the fertility rates before and after RP/IPAA,
      to compare them with the reproductive data of the general United States
      population, and to determine surgical parameters that might influence subsequent
      fertility. METHODS: Three hundred women of reproductive age who underwent RP/IPAA
      between 1983 and 2001 completed a mailed questionnaire regarding their
      reproductive function before and after the procedure. Additional information was
      obtained from the pelvic pouch database. The reproductive information was
      compared to age-matched historical control subjects from the United States
      general population. The associations between changes in fertility and surgical
      parameters were also investigated. RESULTS: The median (25th, 75th percentile)
      age at surgery was 28 (24, 33) years. Out of 300 women, 206 attempted to
      conceive. Before operation, 48 (38%) of 127 patients were unsuccessful after 1
      year of unprotected intercourse, whereas after operation, 76 (56%) of 135
      patients were unsuccessful. This infertility rate was higher after operation than
      before (P <.001). For the subgroup of 56 women who tried to get pregnant both
      before and after operation, the infertility rate was higher after operation than
      before (69% vs 46%; P=.005). Also, a higher percentage of these patients who had
      an intraoperative transfusion were infertile after operation compared to patients
      who did not have an intraoperative transfusion (54% vs 21%; P=.023). CONCLUSIONS:
      There was an increase in the infertility rate after RP/IPAA. Intraoperative blood
      transfusion had a negative impact on the fertility rate after operation in
      patients who tried to conceive both before and after RP/IPAA.

PMID- 15467665
TI  - An initial experience and evolution of laparoscopic hepatic resectional surgery.
AB  - BACKGROUND: The use of minimally invasive procedures has revolutionized modern
      surgery. Only recently has laparoscopy been introduced for use in hepatic
      surgery. METHODS: Patient demographics, tumor characteristics, and outcomes were
      evaluated for all initial cases of laparoscopic hepatic resection. RESULTS:
      Twenty-one resections were performed in 17 patients; 5 were performed for
      malignancy, of which 3 had underlying cirrhosis, and the remaining 12 for benign
      symptomatic disease. Mean patient age was 55.4 (range, 24-82 years). The mean
      number of lesions was 1.4 (range, 1-5), having an average size of 7.6 cm (range,
      2-30 cm). Mean operative time was 2.8 hours (range, 2-5 hours) hours. Most
      resections involved 1 or more Couinaud segments. Mean blood loss was 288 cc
      (range, 50-150 cc). Complications included re-operation for hemorrhage (n=2),
      biliary leakage (n=1), and death from hepatic failure (n=1). Mean length of stay
      was 2.9 days (range, 1-14). When compared with our series of 100 patients who
      underwent open hepatic resection for benign tumors, significantly greater means (
      P <.05) were noted for blood loss (485 cc), operative time (4.5 hours), and
      length of stay (6.5 days). CONCLUSIONS: Laparoscopic hepatic surgery, though
      complex, can be performed safely and efficaciously. Minimally invasive surgery
      appears to provide several distinct advantages over traditional open hepatic
      surgery. However, techniques for the laparoscopic control of bleeding and bile
      leak remain in their infancy.

PMID- 15467666
TI  - Diffusion of new technology in health care: the case of aorto-iliac occlusive
      disease.
AB  - BACKGROUND: The objective of the current study was to characterize temporal
      trends in the treatment of aorto-iliac occlusive disease (AIOD) and the impact of
      the introduction of less invasive therapy on overall intervention rates. METHODS:
      Patients with diagnostic codes for AIOD, and procedure codes for aortofemoral
      bypass (AFB) or iliac artery angioplasty and stenting were selected from the
      Nationwide Inpatient Sample for 1996 to 2000. Utilization rates of both
      intervention types were determined. Outcome variables including in-hospital
      mortality and duration of stay were assessed. RESULTS: The rate of iliac artery
      angioplasty and stenting increased 850%, from 0.4 to 3.4 cases per 100,000 adults
      (P <.001). The rate of AFB declined 15.5%, from 5.8 to 4.9 cases per 100,000
      adults (P <.005). Older age, white race, and higher-income patients were more
      likely to undergo angioplasty and stenting. AFB had a higher mortality rate,
      longer duration of stay, and higher hospital charges compared to angioplasty and
      stenting. CONCLUSIONS: Iliac artery angioplasty and stenting has rapidly gained a
      large market share in the treatment of AIOD. Acceptable clinical outcomes have
      likely lowered the threshold for treatment and contributed to the rapid diffusion
      of this technology for the treatment of AIOD.

PMID- 15467667
TI  - Mapping the phrenic nerve motor point: the key to a successful laparoscopic
      diaphragm pacing system in the first human series.
AB  - BACKGROUND: For patients with high spinal cord injury and chronic respiratory
      insufficiency, electrically induced diaphragm pacing is an alternative to long
      term positive pressure ventilation. The goal of this study was to
      laparoscopically assess the phrenic nerve motor point of the diaphragm and then
      implant electrodes to produce chronic negative pressure ventilation. METHODS:
      Patients undergoing elective laparoscopic procedures (volunteer patient group)
      underwent a series of electrical stimuli (2 to 24 mA at 100-microsecond pulse
      widths) with a mapping probe to identify the motor point through qualitative
      visualization of diaphragm motion and quantitative measurement of the abdominal
      pressure to assess the strength of the contraction. After Food and Drug
      Administration and Institutional Review Board approval, tetraplegic patients
      (spinal cord injured patient group) who were ventilator dependent underwent
      mapping and implantation of electrodes for pacing in both diaphragms. RESULTS: In
      the volunteer group, 28 patients underwent 3 to 50 stimulations per diaphragm to
      identify the motor points. Throughout this series the surgical tools and software
      were improved to allow rapid motor point location with a grid-mapping algorithm.
      In the spinal cord injured group, 5 of 6 patients had electrodes successfully
      implanted at the motor point to produce adequate tidal volumes. The one failure
      caused a change in our inclusion criteria to include fluoroscopic confirmation of
      diaphragm movement during surface nerve stimulation. Three patients are
      completely free of the ventilator, and the other 2 are progressively increasing
      their time off the ventilator with conditioning. CONCLUSIONS: Mapping and
      implantation of the electrodes can be done laparoscopically, providing for a low
      risk, cost-effective, outpatient, diaphragm pacing system that will support the
      respiratory needs of patients.

PMID- 15467668
TI  - An effective pyloromyotomy length in infants undergoing laparoscopic
      pyloromyotomy.
AB  - BACKGROUND: Traditional management of pyloric stenosis has consisted of open
      pyloromyotomy during which the surgeon is able to palpate and determine whether
      the hypertrophied pylorus has been completely divided. During the last decade,
      laparoscopic pyloromyotomy has become an increasingly popular approach for this
      condition. The purpose of this study was to determine whether there is an
      effective pyloromyotomy length that will allow the surgeon to feel confident that
      a complete pyloromyotomy was performed with the laparoscopic approach. METHODS:
      All infants undergoing laparoscopic pyloromyotomy from October 1999 through
      October 2003 at a single institution were retrospectively studied. Clinical
      variables collected included the patient's age, gender, electrolyte status on
      admission, the elapsed time from admission to operation, ultrasonographic
      dimensions of the hypertrophied pylorus, operative time, the length of the
      pyloromyotomy performed, the time to initial and to full feedings, and the
      duration of the postoperative hospitalization. RESULTS: One hundred seventy-one
      patients comprised the study group. The age (mean +/- standard deviation) at the
      time of operation was 5.2 +/- 2.8 weeks. The mean preoperative ultrasonic
      measurements for both pyloric thickness and pyloric length were 4.3 +/- 0.7 mm
      and 19.5 +/- 2.8 mm, respectively. The average pyloromyotomy incision length for
      this entire group was 1.9 +/- 0.21 cm. The mean operative time was 23.5 +/- 8.3
      minutes. There were no mucosal perforations, no conversions to an open procedure,
      and no evidence for an incomplete pyloromyotomy. CONCLUSIONS: Laparoscopic
      pyloromyotomy is a safe and effective technique for infants with pyloric
      stenosis. A pyloromyotomy incision length of approximately 2 cm appears to be an
      effective measure of a complete pyloromyotomy.

PMID- 15467669
TI  - Mutual reporting of process and outcomes enhances quality outcomes for colon and
      rectal resections.
AB  - BACKGROUND: This report describes the favorable results of mutual reporting of
      process and outcome of care for major resections of the colon and rectum, one of
      six focal points for the Center for Medicare Services studies seeking to broadly
      reduce death and complications and enhance consistency of care. METHODS: A group
      of 66 surgical specialists in 9 cities in Kentucky reported cases to a quality
      improvement network over the past 5 years, and these data were supplemented by
      chart verification and patient satisfaction surveys. Consecutive colon and rectal
      resections (N=309) were reported by 23 general and colorectal surgeons. Eighty
      percent of the operations were performed by 4 surgeons. RESULTS: Forty-four
      percent of the patients had colorectal cancer, and 27% had diverticulitis; 84% of
      colon resections were performed by general surgeons whereas 77% of rectal
      resections were performed by colorectal specialists. Audit showed 6
      leaks/fistulas and 16 patients who required unscheduled readmissions. Eleven
      patients had prolonged ileus. Only 2 patients died. Consensus among network
      surgeons included the following: 1. Mutual reporting led to a narrowing of
      choices and improved timing for antibiotic prophylaxis. 2. Standard order sets in
      one hospital led to a shortened duration of stay. 3. Surgeon participation in a
      quality improvement network led to a safe reduction in preoperative cardiology
      consultation. 4. More patients arrive with all evaluations complete due to
      increased utilization of preoperative anesthesiology clinics. 5. Enhanced
      operating room throughput has been achieved by joint anesthesia/surgery reporting
      and includes reduced time to induction of anesthesia and in the Post-Anesthesia
      Care Unit and lessened use of expensive postoperative antiemetics. 6. Reported
      medication errors were reduced by standard order sets, as were other reported
      adverse events. CONCLUSIONS: Practicing surgeons meet and/or exceed published
      benchmarks for colorectal resections and can further improve their outcomes by
      standardization and refinement of orders and procedures and improved
      collaboration with anesthesiologists.

PMID- 15467670
TI  - Pelvic ring fractures: implications of vehicle design, crash type, and occupant
      characteristics.
AB  - BACKGROUND: Pelvic ring fractures (PRFs) are a major cause of morbidity and
      mortality in motor vehicle collisions (MVCs). Understanding the factors leading
      to PRFs may help improve vehicle design and safety. This study sought to
      determine the vehicular, crash, and occupant characteristics that contribute to
      PRFs. METHODS: From 1997 to 2003, 240 adult patients involved in lateral or
      frontal crashes were prospectively studied. Comprehensive crash reconstructions,
      vehicle analysis, and occupant data were compiled and analyzed as part of the
      national Crash Injury Research Engineering Network project. RESULTS: Of 240 study
      patients, 38 had PRFs. The incidence of PRFs was significantly associated with
      female gender, lateral impact crashes, vehicle incompatibility, and severity of
      crash. Seat belts and airbags were not protective against PRFs in either lateral
      or frontal crashes. CONCLUSIONS: All vehicles in the current study were less than
      6 years old at the time of the MVC and thus reflect newer safety designs.
      Compared with studies of PRFs in MVCs before the widespread adoption of modern
      safety standards, our series suggests there has been a modest decrease in the
      incidence of PRFs in newer vehicles. Current safety standards do not adequately
      protect against PRFs, especially in lateral MVCs involving incompatibility and
      female occupants. New technology needs to be developed and implemented. Our data
      suggest that side impact airbags, alteration of vehicle geometry, and increased
      reinforcement of side panels and doors may result in fewer PRFs.

PMID- 15467671
TI  - Heparin-associated antiplatelet antibodies increase morbidity and mortality in
      hemodialysis patients.
AB  - BACKGROUND: Patients are frequently exposed to heparin during hemodialysis (HD)
      to prevent thrombosis of the extracorporeal circuit. Other groups with frequent
      heparin exposures have a high rate of development of heparin-associated
      antiplatelet antibodies (HAAb). We sought to define the prevalence of HAAb in HD
      patients and evaluate their effects. METHODS: A chart listing of all patients
      undergoing HD at our tertiary care institution during a six-year period was
      obtained. Charts of patients who tested positive for HAAb were reviewed. A cohort
      of randomly selected HD patients who tested negative for HAAb was analyzed as a
      control group. RESULTS: In our sample, 3.7% of HD patients were positive for
      HAAb. Morbidity, as defined by thromboembolic (TEC) or hemorrhagic complications,
      was higher in the HAAb-positive group compared with the control patients (60% vs
      8.7%, P < .05), and the mortality rate (mortality directly related to TECs) was
      also higher in the HAAb-positive patients (28.6% vs 4.35%, P < .05). CONCLUSIONS:
      Contrary to reports of HAAb in patients undergoing HD without increased morbidity
      and mortality, we found significant increases in both morbidity and mortality.
      The elevated morbidity and mortality may represent ongoing endothelial and
      platelet activation from repeated heparin exposures. Reduced morbidity and
      mortality will likely require early recognition of HAAb and alteration of
      anticoagulation in HD patients.

PMID- 15467672
TI  - Radiographic underestimation of small bowel stricturing Crohn's disease: a
      comparison with surgical findings.
AB  - BACKGROUND: The purpose of this study was to determine the accuracy of barium
      radiography compared with intraoperative evaluation with passage of a balloon
      catheter for assessment of stricturing Crohn's disease (CD). METHODS: After
      institutional review board approval, we retrospectively reviewed a tertiary
      inflammatory bowel disease center's consecutive records of surgical patients
      between 1998 and 2003 with small intestinal CD to compare the number of
      strictures found at surgery with those identified preoperatively by barium
      imaging. Age, gender, prior surgical procedures, and steroid usage were recorded.
      By decision of the surgeons, all patients were treated with an identical approach
      that utilized intraluminal sizing with passage of a balloon-tipped catheter.
      RESULTS: In 118 patients, 230 strictures were identified by barium examination;
      365 strictures were identified using the balloon catheter technique. Barium
      examination overestimated or underestimated the number of strictures in 43 of 118
      patients (36%). Overall, barium radiography was least accurate in patients with
      strictures amenable to strictureplasty. Prior surgery and multiple strictures
      identified preoperatively by barium studies were found to decrease the accuracy
      of the barium examination, but the decrease did not reach statistical
      significance. After successful surgery for stricturing small intestinal CD, more
      than 90% of patients can successfully be weaned from their steroids within 3
      months. Failure to be able to wean from steroids may suggest a missed stricture.
      CONCLUSIONS: Our data suggest that careful exploration and intraoperative,
      intraluminal testing of intestinal patency identify additional strictures
      compared with barium radiographs in a significant number of patients with CD
      undergoing small bowel surgical intervention.

PMID- 15467673
TI  - Resident perceptions of the impact of work-hour restrictions on health care
      delivery and surgical education: time for transformational change.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education has recently
      enacted an 80-hour workweek, which has been in effect in New York State for
      several years. We surveyed surgical residents from all four State University of
      New York (SUNY) surgical programs to determine their perceptions of the impact of
      the 80-hour workweek on patient care, surgical education, and personal life.
      METHODS: A survey instrument to address the three areas of concern was developed
      and administered to all surgical residents at the four SUNY programs. Anonymity
      of the responders was maintained. Responses to the questions were in numeric rank
      scores and were analyzed by descriptive statistics, chi-square analysis, and
      analysis of variance. RESULTS: Response rate was 59%. Factors perceived to be
      affected negatively by the residents were continuity and safety of care, their
      operative experience, and their relations with attendings. The factors affected
      positively were increased personal time and decreased fatigue at work.
      Interestingly, the latter did not appear to decrease the rate of medical errors
      in their perception. CONCLUSIONS: The 80-hour workweek has the potential to have
      adverse effects on patient care despite improving the level of fatigue at work.
      Reengineering the surgical residencies will be needed to take full advantage of
      the restricted work hours.

PMID- 15467674
TI  - Prospective evaluation of sestamibi scan, ultrasonography, and rapid PTH to
      predict the success of limited exploration for sporadic primary
      hyperparathyroidism.
AB  - BACKGROUND: The aim of this study was to determine the ability of localizing
      studies and rapid intraoperative parathyroid hormone (PTH) to predict the success
      of a limited approach in patients who then underwent bilateral exploration.
      METHODS: Preoperative sestamibi-iodine subtraction scan and neck ultrasonography
      (US) were used to direct a focal (1-gland) and unilateral (1-sided) parathyroid
      exploration by using rapid intraoperative PTH determinations in 350 patients with
      sporadic primary hyperparathyroidism. Regardless of the findings, the
      contralateral side was then explored. RESULTS: A single gland was predicted by
      sestamibi in 290 patients (83%), US in 298 patients (85%), and concordance of
      both in 205 patients (59%). Unilateral parathyroid exploration, directed by these
      studies, would correctly identify single-gland disease in only 68%, 74%, and 79%,
      respectively. The addition of intraoperative PTH would increase the success rate
      to 73%, 77%, and 82%, respectively. The finding of 2 normal or 2 abnormal glands
      on 1 side would force bilateral exploration, and additional unsuspected pathology
      was found in 13%, 13%, and 9%, respectively. This failure rate would increase to
      21%, 18%, and 15%, respectively, if the analysis assumed a focal rather than
      unilateral approach to the initial exploration. CONCLUSIONS: Even in patients
      with concordant sestamibi and US scans, and an appropriate PTH drop, additional
      abnormal parathyroid glands were found on complete exploration in 15%. A
      bilateral approach offers the best opportunity for the long-term cure of primary
      hyperparathyroidism.

PMID- 15467675
TI  - Laparoscopic donor nephrectomy 1997 to 2003: lessons learned with 500 cases at a
      single institution.
AB  - BACKGROUND: Laparoscopic live donor nephrectomy (LDN) is a less invasive
      alternative to traditional open nephrectomy that has several potential
      advantages. However, there have been few large series reports describing the
      complications of LDN and the details of their management. METHODS: We performed a
      retrospective review of 500 LDNs performed at our center between October 1997 and
      September 2003. We evaluated preoperative donor characteristics, intraoperative
      parameters and complications, and postoperative recovery and complications. A
      modification of the Clavien classification was developed and used to grade the
      severity of all complications. RESULTS: The overall rate of intraoperative
      complications was 2.8%. There were 9 open conversions (1.8%), of which 6 were in
      the first 100 cases. Six of the 9 open conversions were for management of
      complications; 3 were elective. Seven renovascular incidents (1.4%) all required
      open conversion except one. The overall rate of postoperative complications was
      3.4%. Thirty of 500 patients in our LDN series experienced an intraoperative or
      procedure-related complication (6.0%). When graded by severity, 18 of 31 (58.1%)
      of all complications were grade 1, 11 of 31 (35.4%) grade 2, and 2 of 31 (6.5%)
      grade 3. Only 1 recipient experienced delayed graft function, and only 1
      recipient had a urologic complication. CONCLUSIONS: Our series supports the
      safety and efficacy of LDN with very low intraoperative complication and
      conversion rates. Most of the intraoperative complications can be managed
      laparoscopically. Readmissions are extremely rare (1.5%). Aberrant vascular
      anatomy and obesity are not contraindications to LDN, but they require
      experience. With careful surgical technique, delayed graft function and urologic
      complications in recipients can be avoided. A graded classification scheme for
      reporting complications of donor nephrectomy might be useful for maintaining
      registry information on donor outcomes and when informing potential donors about
      the risks and benefits of this procedure.

PMID- 15467676
TI  - Blunt splenic injury: operation versus angiographic embolization.
AB  - BACKGROUND: Splenic injuries, like other blunt traumatic injuries, are
      increasingly treated with non-operative management. Angiographic embolization
      (AE) has emerged as an alternative modality for treatment of splenic injuries. We
      hypothesized that splenic embolization would lead to equivalent, if not improved,
      outcomes in terms of mortality, total costs, complications, and duration of stay.
      METHODS: A retrospective review of a prospective data set was performed for all
      adult splenic injuries admitted to our level I trauma center from 2000 through
      2003. Demographics, number of red cell units, emergency department hemodynamics,
      costs, and outcomes were examined. The operative group included those who
      underwent computed tomography (CT) first then went to the operating room (OR)
      (CT+OR) or those who went directly to the OR. RESULTS: There were 25 CT+OR and 24
      AE patients of 164 blunt splenic injuries. After univariate analysis, higher
      injury severity score (ISS), lower systolic blood pressure, lower pH, and higher
      packed red blood cell transfusions were associated with increased mortality and
      duration of stay. The splenic Abbreviated Injury Scale (AIS; mean +/- SD) was the
      same for AE compared to CT+OR patients (3.8 +/- 0.4 vs 3.5 +/- 0.9). Although the
      AE group was older (50 +/- 20 vs 36 +/- 13 years, P < .01), Glasgow Comma Score
      (13 +/- 4 vs 11 +/- 5), age, highest heart rate (109 +/- 24 vs 120 +/- 43), and
      splenic AIS were not predictive of the need for an operation. Abdominal
      complications were lower in the AE group compared to the CT+OR (13% vs 29%), but
      mortality was not different (8% vs 4%). Total costs were similar for both groups
      after adjustment for ISS, GCS, pH, pretreatment transfusions, and spleen AIS (AE,
      $49,300 +/- $40,460 vs CT+OR, $54,590 +/- $34,760). The non-operative failure
      rate in this study was 2%. CONCLUSIONS: AE of splenic injuries is safe and
      associated with fewer complications. The spleen AIS, heart rate, age, and GCS did
      not correlate with the need for an operation. Higher ISS, lower blood pressure,
      lower pH, and increased number of packed red blood cell transfusions were better
      indicators of the need for an operation versus embolization.

PMID- 15467678
TI  - Pancreatic duct strictures are a common cause of recurrent pancreatitis after
      successful management of pancreatic necrosis.
AB  - BACKGROUND: Successful surgical management of pancreatic necrosis can result in
      structural changes that cause recurrent pancreatitis. The purpose of this study
      is to review our clinical experience managing recurrent pancreatitis in patients
      after successful pancreatic debridement. METHODS: We retrospectively reviewed 98
      patients with pancreatic necrosis treated by debridement who made a complete
      recovery at our institution over an 8-year period (January 1995 to January 2003).
      RESULTS: Fourteen patients (14%) developed recurrent pancreatitis 5 to 39 months
      (median, 15 months) after recovery. Five patients (36%) had pancreatic
      pseudocysts and 9 (64%) had radiologic evidence of obstructive pancreatitis. All
      patients had either a high-grade pancreatic duct stricture (N=7) or complete duct
      cutoff (N=7), localized to the pancreatic neck (N=10) or proximal pancreatic body
      (N=4) identified by either endoscopic retrograde cholangiopancreatography or
      magnetic resonance cholangiopancreatography. Two patients failed endoscopic stent
      therapy. All patients required re-operative treatment: 6 distal pancreatectomy, 6
      pancreatico-jejunostomy Roux-en-Y, and 2 cystojejunostomy Roux-en-Y with no
      recurrence of pancreatitis after a median follow-up of 22 months. CONCLUSIONS:
      Recurrent pancreatitis occurs in 14% of patients after successful pancreatic
      debridement. Pancreatic duct obstruction in the neck or proximal body is the
      primary etiologic factor. Re-operation directed at alleviating this ductal
      obstruction by resection or drainage is effective.

PMID- 15467677
TI  - Direct peritoneal resuscitation as adjunct to conventional resuscitation from
      hemorrhagic shock: a better outcome.
AB  - BACKGROUND: Conventional resuscitation (CR) from hemorrhagic shock often
      culminates in multisystem organ failure and death, commonly attributed to a
      progressive splanchnic vasoconstriction and hypoperfusion, a gut-derived systemic
      inflammatory response (SIR), and fluid sequestration. Direct peritoneal
      resuscitation (DPR) produces a sustained state of tissue hyperperfusion in
      splanchnic and distant organs. In this study we evaluated the therapeutic
      potential of DPR on the SIR and fluid sequestration as parameters of treatment
      outcome. METHODS: Anesthetized nonheparinized rats continuously monitored for
      hemodynamics were bled to 40% of mean arterial pressure for 60 minutes. Animals
      were randomized for CR or CR plus DPR under aseptic conditions. Sham
      nonhemorrhaged rats served as control. Qualitatively, animals were blindly
      observed for body weight, illness score, or death for 72 hours. Tissues were
      harvested from survivors, and SIR was measured by interleukin (IL)-6, IL-10,
      tumor necrosis factor-alpha, and enzyme-linked immunosorbent assay, and fluid
      sequestration was measured by dry weight/wet weight ratio (DW/WW). RESULTS:
      Adjunct DPR caused a marked increase (P >.01 by analysis of variance) in the
      immunoregulator IL-10 in the liver (10,990 +/- 1,470 pg/g) and gut (1815 +/- 640
      pg/g), compared to CR rats (6450 +/- 1000 pg/g and 1555 +/- 590, respectively),
      which is associated with down-regulation of IL-6 and tumor necrosis factor-alpha
      in liver and gut, from 57 +/- 4 and 20 +/- 3 pg/g, respectively, to 42 +/- 4 and
      9 +/- 2 pg/g in DPR-treated animals. CR animals had a lower DW/WW ratio in liver
      (-36%), spleen (-22%), and lung (-24%) compared to DPR (P <.05), where the DW/WW
      ratio did not differ from control animals. This fluid sequestration is consistent
      with a 12% and 5% gain in prehemorrhage body weight at 24 and 72 hours after
      treatment in the CR animals. Thirty percent of CR animals died within 24 hours,
      and survivors were squeaking, cold, and pale in eyes and ears and oliguric
      despite features of fluid overload. In comparison, DPR animals exhibited normal
      appearance by 24 hours and demonstrated a 100% survival at 72 hours. CONCLUSIONS:
      This study demonstrates that DPR as adjunct to CR has beneficial effects on the
      pathophysiology of resuscitated hemorrhagic shock. In addition to restoration of
      tissue perfusion, DPR has immunomodulation and anti-fluid sequestration effects.
      These modulations result in improved outcome.

PMID- 15467679
TI  - Utility of total mechanical stapled cervical esophagogastric anastomosis after
      esophagectomy: a comparison to conventional anastomotic techniques.
AB  - BACKGROUND: Cervical esophagogastric anastomosis after esophagectomy is often
      troubled with anastomotic leak resulting in local sepsis, postoperative
      stricture, and prolonged hospitalization. We compared the anastomotic outcomes
      and clinical course of esophagectomy patients undergoing total mechanical stapled
      esophagogastric anastomosis versus a partial handsewn/mechanical stapled cervical
      anastomotic technique. METHODS: One hundred eighty-one patients underwent
      transhiatal (N=146) or 3-field (abdomen/chest/neck incisions) (N=35)
      esophagectomy. A total mechanical stapled anastomosis was accomplished in 125
      patients. A handsewn/mechanical stapled anastomosis was performed in 56 patients.
      The total mechanical stapled anastomosis was accomplished by using the endoscopic
      gastrointestinal stapler to construct the posterolateral aspect and a linear
      stapler to close the anterior aspect of the anastomosis. Total mechanical stapled
      anastomosis patients had the endoscopic gastrointestinal stapler also used to
      divide the left gastric vessels and the short gastric mesentery for gastric
      mobilization. Anastomotic outcomes were analyzed by the leak rate (contrast
      study) and the need of serial dilations in each group. CONCLUSIONS: Total
      mechanical stapled technique after esophagectomy with cervical esophagogastric
      anastomosis appears to be effective in reducing hospitalization and anastomotic
      complications compared to partial or complete handsewn techniques. Liberal use of
      endoscopic staplers might shorten operative time. Esophageal surgeons should be
      aware of the advantages and become skilled with these techniques.

PMID- 15467680
TI  - Intrahepatic biliary cystadenoma: role of cyst fluid analysis and surgical
      management in the laparoscopic era.
AB  - BACKGROUND: Recent interest in cyst fluid analysis (CFA) for carbohydrate antigen
      19-9 (CA 19-9) and carcinoembryonic antigen (CEA), and the introduction of
      laparoscopic surgery (LS) in the management of hepatic cysts have resulted in
      sporadic reports of elevated CA 19-9 and CEA levels in intrahepatic biliary
      cystadenoma (IBC) CFA, and the application of LS in the management of simple
      cysts. However, the role of CA 19-9 and CEA in the diagnosis of IBC and the role
      of LS in the management of IBC have not been previously defined. METHODS: We
      studied 34 patients with IBC at a single institution (8 years). The first 12
      patients with IBC were managed with open surgical intervention. We subsequently
      developed a diagnostic and treatment algorithm for IBC that included, in the last
      22 patients, prospective analysis of CFA for CA 19-9 and CEA, and LS for
      management RESULTS: All patients with IBC who underwent CFA had elevated CA 19-9
      (range, 2247-1,757,510; N <33 U/mL) and mildly elevated CEA (range, 3.3-212,; N
      <3 ng/ml). In all 22 patients the cyst lining consisted of biliary epithelium +/-
      mesenchymal stroma (MS). In 1/22 patients (highest CA 19-9 level), the cyst
      epithelium did not contain either MS or intestinal metaplasia. In contrast,
      control patients (simple cysts, n=8) had normal CFA. In the previous 12 patients
      managed with laparotomy, 6/12 patients had biliary epithelium alone; the other 6
      also contained MS with 1 patient exhibiting intestinal metaplasia and
      cystadenocarcinoma. CONCLUSIONS: We have proposed a management algorithm for IBC
      that incorporates CFA and laproscopic surgical management that allows for
      selective minimally invasive cyst wall sampling for patients with IBC.

PMID- 15467681
TI  - Immunoglobulin A protease is a virulence factor for gram-negative pneumonia.
AB  - BACKGROUND: Secretory immunoglobulin A (SIgA) is the principal immunologic
      defense of respiratory and other mucosal surfaces in the body. SIgA is relatively
      stable in mucosal secretions. However, cleavage of SIgA by bacterial proteases
      might render it immunologically inactive and thus contribute to the development
      of pneumonia as well as other infections. Bacterial species and infection sites
      might be important in the expression of bacterial protease activity and serve as
      the impetus to this study. METHODS: Bacterial isolates from respiratory and
      nonrespiratory sites were incubated with SIgA in vitro. SIgA degradation was
      determined by size exclusion ultrafiltration and gel electrophoresis. RESULTS:
      IgA protease activity was evident in gram-negative but not gram-positive
      respiratory isolates. Gram-negative isolates from nonrespiratory sources did not
      exhibit IgA protease activity. CONCLUSIONS: Expression of IgA protease activity
      might be important in the development and subsequent outcome of gram-negative
      pneumonia in the patient in the surgical intensive care unit.

PMID- 15467683
TI  - Political science.

PMID- 15467684
TI  - Looking for design in materials design.
AB  - Despite great advances in computation, materials design is still science fiction.
      The construction of structure-property relations on the quantum scale will turn
      computational empiricism into true design.

PMID- 15467686
TI  - Peering below the surface.

PMID- 15467687
TI  - A step in synthesis.

PMID- 15467688
TI  - Finding order in disorder.

PMID- 15467689
TI  - Precious biosensors.

PMID- 15467690
TI  - Nanocomposites are stretched thin.

PMID- 15467695
TI  - Retinal haemorrhages following Retcam screening for retinopathy of prematurity.

PMID- 15467696
TI  - Endophthalmitis following cataract surgery.

PMID- 15467697
TI  - Photodynamic therapy for age-related macular degeneration.

PMID- 15467698
TI  - Patient-controlled alerting device (PAD).

PMID- 15467699
TI  - Patient alert system: the Edinburgh experience.

PMID- 15467700
TI  - Contrast sensitivity as an outcome measure in patients with subfoveal choroidal
      neovascularisation due to age-related macular degeneration.
AB  - PURPOSE: Although visual acuity is the most frequently used primary outcome
      measure in clinical trials of treatments for choroidal neovascularisation (CNV)
      due to age-related macular degeneration (AMD), contrast sensitivity may provide
      valuable additional information. This paper reviews the evidence for using
      contrast sensitivity as a measure of visual function and as an outcome measure in
      clinical trials in patients with subfoveal CNV due to AMD. METHODS: Medline
      database searches were performed to retrieve relevant articles on contrast
      sensitivity. In addition, articles were included from the authors' knowledge of
      the literature and from the reference lists of retrieved articles. RESULTS: The
      published literature demonstrates that contrast sensitivity is an important
      measure of visual function in patients with subfoveal CNV due to AMD. Most
      clinical trials of treatments for CNV due to AMD have reported visual acuity as
      the primary outcome. However, there is evidence that treatment (such as
      verteporfin therapy) may also provide additional benefits in terms of contrast
      sensitivity. These benefits may not be completely characterised by measurement of
      visual acuity alone. CONCLUSIONS: The inclusion of contrast sensitivity as an
      outcome measure in studies of patients with CNV due to AMD may provide a more
      complete understanding of the effects of treatment on visual function and the
      likely benefits for patients.

PMID- 15467701
TI  - Eyelash poliosis in association with sarcoidosis.

PMID- 15467702
TI  - Usefulness of peripheral anterior chamber depth assessment in glaucoma screening.
AB  - PURPOSE: This study was conducted to determine the usefulness of peripheral
      anterior chamber depth assessment in angle-closure glaucoma (ACG) screening in
      Japanese subjects. SUBJECTS AND METHODS: The subjects were 14,779 adults 40 years
      old or older. Eyes having peripheral anterior chamber depth that is 1/4 the
      peripheral corneal thickness (van Herick's classification: grade 2) and less than
      1/4 the peripheral corneal thickness (van Herick's classification: grade 1) were
      extracted as narrow angle eyes, and those eyes were further examined. RESULTS: Of
      14,779 subjects, 923 eyes of 505 subjects were diagnosed as narrow angle eyes
      (3.4%). Narrow angle eyes were observed in 4.9% of female subjects and 1.9% of
      male subjects, indicating a significantly higher frequency in women. The
      percentage of narrow angle eyes increased with age. Among the narrow angle eyes,
      61 eyes of 32 subjects were diagnosed with ACG suspect (6.5%). In contrast to the
      frequency of ACG suspect in eyes classified as grade 1, according to van Herick's
      classification, being 17.9%, that in eyes classified as grade 2 was significantly
      lower at 5.6%. CONCLUSION: Since the incidence of ACG suspect increases as the
      peripheral anterior chamber depth decreases, caution for the peripheral anterior
      chamber depth is required for the ACG screening.

PMID- 15467704
TI  - Cataract surgery after intravitreal injection of triamcinalone.

PMID- 15467705
TI  - Rose-hip keratitis.

PMID- 15467706
TI  - Purtscher-like retinopathy as an initial presentation of thrombotic
      thrombocytopenic purpura: a case report.

PMID- 15467707
TI  - Panic induction with cholecystokinin-tetrapeptide (CCK-4) Increases plasma
      concentrations of the neuroactive steroid 3alpha, 5alpha
      tetrahydrodeoxycorticosterone (3alpha, 5alpha-THDOC) in healthy volunteers.
AB  - 3alpha-reduced neuroactive steroids such as 3alpha, 5alpha-tetrahydroprogesterone
      (3alpha, 5alpha-THP) and 3alpha, 5alpha-tetrahydrodeoxycorticosterone (3alpha,
      5alpha-THDOC) are potent positive allosteric modulators of gamma-aminobutyric
      acid type A (GABAA) receptors and display pronounced anxiolytic activity in
      animal models. Experimental panic induction with cholecystokinin-tetrapeptide
      (CCK-4) and sodium lactate is accompanied by a decrease in 3alpha, 5alpha-THP
      concentrations in patients with panic disorder, but not in healthy controls.
      However, no data are available on 3alpha, 5alpha-THDOC concentrations during
      experimental panic induction. Therefore, we quantified 3alpha, 5alpha-THDOC
      concentrations in 10 healthy volunteers (nine men, one woman) before and after
      panic induction with CCK-4 by means of a highly sensitive and specific gas
      chromatography/mass spectrometry analysis. CCK-4 elicited a strong panic response
      as assessed by the Acute Panic Inventory. This was accompanied by an increase in
      3alpha, 5alpha-THDOC, ACTH and cortisol concentrations. This increase in 3alpha,
      5alpha-THDOC might be a consequence of hypothalamic-pituitary-adrenal (HPA) axis
      activation following CCK-4-induced panic, and might contribute to the termination
      of the anxiety/stress response following challenge with CCK-4 through enhancement
      of GABAA receptor function.

PMID- 15467708
TI  - Amphetamine-induced Fos is reduced in limbic cortical regions but not in the
      caudate or accumbens in a genetic model of NMDA receptor hypofunction.
AB  - A mouse strain has been developed that expresses low levels of the NR1 subunit of
      the NMDA receptor. These mice are a model of chronic developmental NMDA receptor
      hypofunction and may therefore have relevance to the hypothesized NMDA receptor
      hypofunction in schizophrenia. Many schizophrenia patients show exaggerated
      behavioral and neuronal responses to amphetamine compared to healthy subjects.
      Studies were designed to determine if the NR1-deficient mice would exhibit
      enhanced sensitivity to amphetamine. Effects of amphetamine on behavioral
      activation and Fos induction were compared between the NR1-deficient mice and
      wild-type controls. The NR1 hypomorphic mice and controls exhibited similar
      locomotor activation after administration of amphetamine at 2 mg/kg. The mutant
      mice showed slightly reduced peak locomotor activity and slightly increased
      stereotypy after 4 mg/kg amphetamine. There were no differences in Fos induction
      in response to amphetamine in the caudate putamen, nucleus accumbens, medial or
      central amygdala nuclei, or bed nucleus of the stria terminalis. However,
      amphetamine-induced Fos was substantially attenuated in the medial frontal
      (infralimbic) and cingulate cortices, basolateral amygdala, and in the lateral
      septum of the mutant mice. The results suggest a neuroanatomically selective
      activation deficit to amphetamine challenge in the NR1-deficient mice.

PMID- 15467709
TI  - A survey of clusterin and fascin expression in sarcomas and spindle cell
      neoplasms: strong clusterin immunostaining is highly specific for follicular
      dendritic cell tumor.
AB  - Clusterin, a glycoprotein implicated in many cellular functions including
      apoptosis, has recently been shown to be strongly expressed in follicular
      dendritic cell tumors, and to be absent or only weakly expressed in other
      dendritic cell tumors. Fascin has also been investigated as a potential marker of
      dendritic cell neoplasms. We evaluated staining for antibodies directed against
      these two antigens in 202 spindle cell tumors, including cases of follicular
      dendritic cell tumor (n=14), interdigitating dendritic cell tumor (n=7),
      leiomyosarcoma (n=17), inflammatory myofibroblastic tumor (n=13), inflammatory
      pseudotumor (n=2), spindle cell thymoma (n=17), synovial sarcoma (n=11),
      fibrosarcoma (n=14), liposarcoma (n=27), gastrointestinal stromal tumor (n=13),
      malignant fibrous histiocytoma (n=18), angiomatoid fibrous histiocytoma (n=4),
      angiosarcoma (n=10), malignant peripheral nerve sheath tumor (n=8), malignant
      melanoma (n=16), and spindle cell carcinoma (n=11). Among these spindle cell
      neoplasms, strong diffuse clusterin staining had an overall specificity of 93%
      and a sensitivity of 100% for follicular dendritic cell tumor. Clusterin staining
      was least reliable in distinguishing follicular dendritic cell tumor from spindle
      cell thymoma or malignant fibrous histiocytoma, but these are entities that
      usually can be distinguished by clinical and morphologic data. Rare cases of
      leiomyosarcoma, fibrosarcoma and angiosarcoma may show strong clusterin staining.
      Fascin staining was very nonspecific among spindle cell tumors and thus does not
      imply a dendritic cell lineage.

PMID- 15467710
TI  - Distinct spatial expression patterns of AP-2alpha and AP-2gamma in non-neoplastic
      human breast and breast cancer.
AB  - Although transcription factors AP-2alpha and AP-2gamma have been implicated in
      the control of estrogen receptor (ER) and ErbB-2, their impact for breast cancer
      is still controversial. To better understand the role of AP-2 proteins in mammary
      neoplasia, the analysis of their spatial expression pattern in normal breast and
      breast cancer is required. A total of 51 specimens of female breast cancer
      patients and a tissue microarray containing 93 additional female breast cancer
      cases were immunohistochemically stained for AP-2alpha, AP-2gamma, ER and ErbB-2.
      In 70 cases of the tissue microarray, survival data comprising a period of up to
      30 years were present. In non-neoplastic breast tissue, AP-2alpha was expressed
      in the inner glandular cell layer while AP-2gamma was expressed in the outer
      myoepithelial cell layer. Ductal carcinoma in situ revealed strongly AP-2alpha
      positive tumor cells surrounded by a layer of AP-2gamma-positive myoepithelial
      cells. In invasive carcinoma, expression of AP-2alpha and AP-2gamma was variable.
      High expression of ER and AP-2alpha showed better survival rates than low
      expression of these markers. AP-2gamma expression had no effect on survival.
      These results for the first time reveal a distinct spatial expression pattern of
      AP-2alpha and AP-2gamma in normal breast and in ductal carcinoma in situ with
      specific AP-2gamma expression in myoepithelium. High ER and AP-2alpha expression
      in invasive breast cancer showed favorable survival rates. Therefore, AP-2alpha
      expression seems to be associated with better prognosis of breast cancer. AP
      2gamma expression has no influence on survival reflecting that myoepithelial
      cells are not involved in the neoplastic process.

PMID- 15467711
TI  - Erythropoietin and erythropoietin receptor expression in human prostate cancer.
AB  - Erythropoietin is a hematopoietic cytokine that regulates the production of red
      blood cells. Erythropoietin is normally produced in the adult kidney in a hypoxia
      inducible manner. The recombinant form of human erythropoietin is in clinical use
      for the prevention and treatment of anemia that is associated with cancer and its
      treatment with chemoradiation therapy. A series of recent studies from our
      laboratory and others have reported the expression of receptors for
      erythropoietin in several different types of human cancer cells. In the present
      study, we investigated the expression of erythropoietin receptor and its ligand
      erythropoietin in human prostate cancer. In clinical specimens of prostate
      cancer, we found abundant expression of erythropoietin receptor protein in all
      primary tumors examined using immunohistochemistry. Furthermore, we observed
      erythropoietin coexpression in prostate cancer cells by immunohistochemical
      analysis. To determine whether monolayer cultures of continuous cell lines
      derived from prostate cancer also express erythropoietin receptor and
      erythropoietin, we studied well-characterized hormone-responsive (LNCaP) and
      hormone-refractory (PC-3) prostate cancer cell lines. We performed reverse
      transcription and polymerase chain reaction assays to detect erythropoietin
      receptor and erythropoietin mRNA transcripts, and also immunoprecipitation and
      immunoblotting to detect erythropoietin receptor protein expression in prostate
      cancer cells. These experiments revealed the expression of both erythropoietin
      receptor and erythropoietin in LNCaP and PC-3 cells suggesting that these
      prostate cancer cell lines may serve as useful experimental models for further
      studies of erythropoietin and erythropoietin receptor function in prostate
      cancer. The coexpression of erythropoietin receptor and its ligand erythropoietin
      in human prostate cancer cells suggests the potential for growth regulation by
      erythropoietin-erythropoietin receptor in an autocrine or paracrine manner.

PMID- 15467712
TI  - Promoter methylation profiles of tumor suppressor genes in intrahepatic and
      extrahepatic cholangiocarcinoma.
AB  - Recent studies indicate that tumor suppressor genes can be epigenetically
      silenced through promoter hypermethylation. To further understand epigenetic
      alterations in cholangiocarcinoma, we have studied the methylation profiles of 12
      candidate tumor suppressor genes (APC, E-cadherin/CDH1, MGMT, RASSF1A, GSTP, RAR
      beta, p14ARF, p15INK4b, p16INK4a, p73, hMLH1 and DAPK) in 72 cases of
      cholangiocarcinoma, including equal number cases of intrahepatic
      cholangiocarcinoma and extrahepatic cholangiocarcinoma. A total of 10 cases of
      benign biliary epithelia were included as controls. The methylation status of
      tumor suppressor genes was analyzed using methylation-specific PCR. We found that
      85% of all cholangiocarcinomas had methylation of at least one tumor suppressor
      gene. The frequency of tumor suppressor gene methylation in cholangiocarcinoma
      was: RASSF1A (65%), p15INK4b (50%), p16INK4a (50%), APC (46%), E-cadherin/CDH1
      (43%), p14(ARF) (38%), p73 (36%), MGMT (33%), hMHL1 (25%), GSTP (14%), RAR-beta
      (14%) and DAPK (3%). Although single tumor suppressor gene methylation can be
      seen in benign biliary epithelium, methylation of multiple tumor suppressor genes
      is only seen in cholangiocarcinoma. About 70% (50/72) of the cholangiocarcinomas
      had three or more tumor suppressor genes methylated and 52% (38/72) of cases had
      four or more tumor suppressor genes methylated. Concerted methylation of multiple
      tumor suppressor genes was closely associated with methylation of RASSF1A, p16
      and/or hMHL1. Methylation of RASSF1A was more common in extrahepatic
      cholangiocarcinoma than intrahepatic cholangiocarcinoma (83 vs 47%, P=0.003)
      while GSTP was more frequently seen in intrahepatic compared to extrahepatic
      cholangiocarcinoma (31 vs 6%, P=0.012). Our study indicates that methylation of
      promoter CpG islands of tumor suppressor genes is a common epigenetic event in
      cholangiocarcinoma. Based on distinct methylation profiles, intrahepatic
      cholangiocarcinoma and extrahepatic cholangiocarcinoma are two closely related
      but biologically unique neoplastic processes. Taking advantage of the unique
      concurrent methylation profile of multiple genes in cholangiocarcinoma may
      facilitate the distinction of cholangiocarcinoma from benign biliary epithelium
      in clinical settings.

PMID- 15467713
TI  - Eosinophilic and classic chromophobe renal cell carcinomas have similar frequent
      losses of multiple chromosomes from among chromosomes 1, 2, 6, 10, and 17, and
      this pattern of genetic abnormality is not present in renal oncocytoma.
AB  - That chromophobe renal cell carcinoma has an uncommon eosinophilic variant has
      been recognized for more than a decade. In sections stained with hematoxylin and
      eosin, the eosinophilic variant of chromophobe renal cell carcinoma and renal
      oncocytoma are similar in appearance. While it is well established that
      chromophobe renal cell carcinoma and renal oncocytoma have different patterns of
      genetic anomalies, little is known of the genetics of the eosinophilic variant of
      chromophobe renal cell carcinoma. This study was undertaken to elucidate the
      genetic lesions of eosinophilic chromophobe renal cell carcinoma and to compare
      them with those found in classic chromophobe renal cell carcinoma and in renal
      oncocytoma. A total of 29 renal neoplasms--nine eosinophilic chromophobe renal
      cell carcinomas, 10 classic chromophobe renal cell carcinomas, and 10 oncocytomas
      -were investigated by fluorescence in situ hybridization on 5 microm paraffin
      embedded tissue sections with centromeric probes for chromosomes 1, 2, 6, 10, and
      17. Signals were counted in 100-200 neoplastic nuclei from each tumor.
      Chromophobe renal cell carcinomas frequently showed loss of chromosomes 1 (70% of
      classic, 67% of eosinophilic), 2 (90% classic, 56% eosinophilic), 6 (80% classic,
      56% eosinophilic), 10 (60% classic, 44% eosinophilic), and 17 (90% classic, 78%
      eosinophilic); Among the classic chromophobe renal cell carcinomas, only one had
      no loss of any of the chromosomes, while 50% had loss of all five chromosomes.
      Among the eosinophilic chromophobe renal cell carcinomas, one of nine had no loss
      and 44% had loss of all five chromosomes. One oncocytoma had loss of chromosome
      1. No other chromosomal loss was detected in the oncocytomas. In conclusion,
      losses of chromosomes 1, 2, 6, 10, and 17 are frequent in both eosinophilic and
      classic chromophobe renal cell carcinomas. Loss of chromosome 1 occurs
      occasionally in oncocytoma but losses of chromosomes 2, 6, 10, and 17 are not
      found in oncocytomas. When the differential diagnostic problem is oncocytoma vs
      eosinophilic chromophobe renal cell carcinoma, detection of losses of chromosomes
      2, 6, 10, or 17 effectively excludes the diagnosis of oncocytoma and supports the
      diagnosis of chromophobe renal cell carcinoma.

PMID- 15467714
TI  - Expression profile of tuberin and some potential tumorigenic factors in 60
      patients with uterine leiomyomata.
AB  - Human uterine leiomyomata are the most common tumors in women of reproductive
      age. The pathogenesis of leiomyomata remains unknown. An animal model of Eker
      rats with deleted tuberous sclerosis complex gene 2 (tuberin) shows increased
      incidence of leiomyomata. The role of tuberin in human leiomyomata is unknown. In
      this study, we designed a tissue microarray with tissue cores of leiomyomata and
      the matched myometrium from 60 hysterectomy specimens. We examined the expression
      of tuberin and tuberous sclerosis complex gene 1 product hamartin, proteins of
      the insulin-signaling pathway, steroid receptors and some of their cofactors, and
      human mobility group gene A2 by immunohistochemistry. We found that nearly half
      of the cases displayed either reduction or loss of tuberin in leiomyomata
      compared with matched normal myometrium. No change of hamartin was noted.
      Furthermore, a significant reduction of glucocorticoid receptor was found in
      leiomyomata with reduced tuberin. The proteins insulin like growth factor 1,
      insulin-like growth factor receptor beta, AKT kinase, and phosphatidylinositol 3
      kinase were upregulated. Nearly half of leiomyomata show upregulation of human
      mobility group gene A2, along with the steroid receptor cofactors. Our findings
      suggest that there are two broad groups of uterine leiomyomata. One group is
      associated with an alteration of tuberin and glucocorticoid receptor. The other
      group is associated with upregulation of human mobility group gene A2 and steroid
      receptor cofactors.

PMID- 15467715
TI  - Spitz nevi and atypical Spitz nevi/tumors: a histologic and immunohistochemical
      analysis.
AB  - A subset of Spitz nevi poses substantial diagnostic difficulty, even among
      experts, due to its resemblance to malignant melanoma. These lesions are termed
      atypical Spitz nevi/tumors and there is currently a lack of objective criteria
      for predicting their biologic behavior. We compared the expression of Ki-67, p21,
      and fatty acid synthase by immunohistochemistry in 10 atypical Spitz nevi, 28
      typical Spitz nevi, 19 compound melanocytic nevi and 18 invasive malignant
      melanomas. There was a progressive increase in fatty acid synthase cytoplasmic
      expression with statistically significant differences observed between Spitz nevi
      and atypical Spitz nevi (P=0.003) and between atypical Spitz nevi and malignant
      melanoma (P<0.050). Ki-67 nuclear staining was lower in both typical and atypical
      forms of Spitz lesions than in malignant melanoma (P<0.001). The degree of P21
      nuclear expression in atypical Spitz nevi was not significantly different than in
      Spitz nevi, but was significantly greater than expression in conventional nevi
      and approached significance after multiple comparisons corrections for malignant
      melanoma. Thus, a high level of P21 expression makes a tumor more likely to be a
      typical or atypical Spitz nevus than a malignant melanoma, especially when
      coupled with a low Ki-67 index and weak expression of fatty acid synthase. These
      immunohistochemical observations support the concept that atypical Spitz nevi are
      distinct lesions of borderline biologic behavior residing between Spitz nevi and
      malignant melanoma. The study also compared a large array of histologic features
      of 16 cases of typical Spitz nevi in children with 12 typical Spitz nevi in
      adults. The adult lesions were significantly more likely to be intradermal and to
      display dermal fibroplasia, but were histologically similar to their pediatric
      counterparts in all other respects.

PMID- 15467716
TI  - Low D2-40 immunoreactivity correlates with lymphatic invasion and nodal
      metastasis in early-stage squamous cell carcinoma of the uterine cervix.
AB  - Lymphatic invasion and nodal metastasis are predictors of shorter disease-free
      and overall survival in carcinoma of the uterine cervix. The monoclonal antibody
      D2-40, which reacts with the oncofetal membrane antigen M2A, is a new selective
      marker for lymphatic endothelium, and has been shown to be useful in identifying
      the presence of lymphatic invasion in various malignant neoplasms, including
      cervical carcinoma. However, the reactivity of the tumor cells with D2-40 has not
      yet been evaluated. In this study, we examined the pattern of D2-40
      immunoreactivity in a series of 138 invasive squamous cell carcinomas of the
      uterine cervix. We correlated the presence and extent of D2-40 immunoreactivity
      in the tumor cells with various clinicopathologic features, the presence of
      lymphatic invasion, lymph node metastasis and outcome. Diffuse or focal D2-40
      immunoreactivity was present in 17 (12%) and 81 (59%) tumors, respectively, while
      40 (29%) tumors showed no immunoreactivity. Lymphatic invasion and nodal
      metastasis were present in 56 and 29% of tumors, respectively. Tumor emboli
      within lymphatic spaces and metastatic tumor foci in lymph nodes showed no
      immunoreactivity in 86 and 80% of the cases, respectively. Lymphatic invasion and
      nodal metastasis were significantly more common in tumors showing low D2-40
      immunoreactivity (P<0.0001 and 0.022, respectively). D2-40 immunoreactivity
      showed no correlation with any other clinicopathologic features examined,
      including tumor size, grade and FIGO stage. In univariate analysis low D2-40
      immunoreactivity was significantly associated with shorter recurrence-free, but
      not with overall survival. Our studies suggest that D2-40 immunostaining may
      serve as a marker for increased risk of lymphatic invasion and tumor recurrence
      in cervical biopsy material. Further study of the biological function of the M2A
      antigen may shed some light on the interaction of tumor cells with lymphatics.

PMID- 15467717
TI  - von Willebrand factor expression in osteosarcoma metastasis.
AB  - A number of genes are implicated in the initiation and progression of
      osteosarcoma; however, cytogenetic and comparative genomic hybridization studies
      indicate the involvement of additional unidentified genes. An examination of gene
      expression profiles in 22 high-grade osteosarcoma tumor specimens from 15
      patients (including paired primary and metastatic samples from five patients)
      indicated that von Willebrand factor (vWF) mRNA expression may increase during
      tumor progression. vWF, a large glycoprotein previously considered to be
      expressed exclusively by endothelial cells and megakaryocytes, is involved in
      platelet aggregation and adhesion to the subendothelial matrix, processes
      critical to hematogenous tumor cell metastasis to the lung. Analysis of paired
      primary and metastatic osteosarcoma tumor samples from 10 patients revealed an
      increase in vWF gene expression in metastases (P=0.005). Immunohistochemistry
      showed that, in addition to the endothelial cells, vWF protein was also detected
      in osteosarcoma cells in vivo in 13 of 29 tumor specimens as well as in SAOS2, an
      osteosarcoma cell line. The tumor cell staining correlated positively with high
      vWF expression in the sample (P=0.006). Although vascular endothelial cells
      contribute to the vWF mRNA detected in the tumor samples, there was neither any
      correlation between vascular density (VD) and vWF mRNA expression nor between VD
      and clinical outcome. These findings suggest that vWF expression is deregulated
      in osteosarcoma tumors, potentially contributing to metastasis.

PMID- 15467718
TI  - Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin
      insensitive.
AB  - The target of rapamycin (TOR) is a highly conserved protein kinase and a central
      controller of cell growth. In budding yeast, TOR is found in structurally and
      functionally distinct protein complexes: TORC1 and TORC2. A mammalian counterpart
      of TORC1 (mTORC1) has been described, but it is not known whether TORC2 is
      conserved in mammals. Here, we report that a mammalian counterpart of TORC2
      (mTORC2) also exists. mTORC2 contains mTOR, mLST8 and mAVO3, but not raptor. Like
      yeast TORC2, mTORC2 is rapamycin insensitive and seems to function upstream of
      Rho GTPases to regulate the actin cytoskeleton. mTORC2 is not upstream of the
      mTORC1 effector S6K. Thus, two distinct TOR complexes constitute a primordial
      signalling network conserved in eukaryotic evolution to control the fundamental
      process of cell growth.

PMID- 15467719
TI  - Transcranial magnetic stimulation of the occipital pole interferes with verbal
      processing in blind subjects.
AB  - Recent neuroimaging studies in blind persons show that the occipital cortex,
      including the primary visual cortex (V1), is active during language-related and
      verbal-memory tasks. No studies, however, have identified a causal link between
      early visual cortex activity and successful performance on such tasks. We show
      here that repetitive transcranial magnetic stimulation (rTMS) of the occipital
      pole reduces accuracy on a verb-generation task in blind subjects, but not in
      sighted controls. An analysis of error types revealed that the most common error
      produced by rTMS was semantic; phonological errors and interference with motor
      execution or articulation were rare. Thus, in blind persons, a transient 'virtual
      lesion' of the left occipital cortex interferes with high-level verbal processing

PMID- 15467720
TI  - Evidence in the Legionella pneumophila genome for exploitation of host cell
      functions and high genome plasticity.
AB  - Legionella pneumophila, the causative agent of Legionnaires' disease, replicates
      as an intracellular parasite of amoebae and persists in the environment as a free
      living microbe. Here we have analyzed the complete genome sequences of L.
      pneumophila Paris (3,503,610 bp, 3,077 genes), an endemic strain that is
      predominant in France, and Lens (3,345,687 bp, 2,932 genes), an epidemic strain
      responsible for a major outbreak of disease in France. The L. pneumophila genomes
      show marked plasticity, with three different plasmids and with about 13% of the
      sequence differing between the two strains. Only strain Paris contains a type V
      secretion system, and its Lvh type IV secretion system is encoded by a 36-kb
      region that is either carried on a multicopy plasmid or integrated into the
      chromosome. Genetic mobility may enhance the versatility of L. pneumophila.
      Numerous genes encode eukaryotic-like proteins or motifs that are predicted to
      modulate host cell functions to the pathogen's advantage. The genome thus
      reflects the history and lifestyle of L. pneumophila, a human pathogen of
      macrophages that coevolved with fresh-water amoebae.

PMID- 15467721
TI  - Recombination rate and reproductive success in humans.
AB  - Intergenerational mixing of DNA through meiotic recombinations of homologous
      chromosomes during gametogenesis is a major event that generates diversity in the
      eukaryotic genome. We examined genome-wide microsatellite data for 23,066
      individuals, providing information on recombination events of 14,140 maternal and
      paternal meioses each, and found a positive correlation between maternal
      recombination counts of an offspring and maternal age. We postulated that the
      recombination rate of eggs does not increase with maternal age, but that the
      apparent increase is the consequence of selection. Specifically, a high
      recombination count increased the chance of a gamete becoming a live birth, and
      this effect became more pronounced with advancing maternal age. Further support
      for this hypothesis came from our observation that mothers with high oocyte
      recombination rate tend to have more children. Hence, not only do recombinations
      have a role in evolution by yielding diverse combinations of gene variants for
      natural selection, but they are also under selection themselves.

PMID- 15467722
TI  - Amplification of IFN-alpha-induced STAT1 activation and inflammatory function by
      Syk and ITAM-containing adaptors.
AB  - A key function of interferons is priming multiple cell types for enhanced
      activation by cytokines and inflammatory factors, including tumor necrosis
      factor, bacterial lipopolysaccharide and interferons themselves. Here we show
      that interferon-alpha (IFN-alpha)-induced activation of the transcriptional
      activator STAT1 and inflammatory STAT1 target genes was enhanced in IFN-gamma
      primed macrophages. Enhanced IFN-alpha signaling and proinflammatory function
      were dependent on the tyrosine kinase Syk and on adaptor proteins that activate
      Syk through immunoreceptor tyrosine activation motifs. Increased STAT1 expression
      contributed to enhanced IFN-alpha-induced STAT1 activation in primed macrophages.
      These results identify a mechanism by which crosstalk between cytokine and immune
      cell-specific immunoreceptor tyrosine activation motif-dependent signaling
      pathways regulates macrophage responses to IFN-alpha.

PMID- 15467723
TI  - CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86.
AB  - Bidirectional signaling along the B7-CTLA-4 coreceptor pathway enables reciprocal
      conditioning of T cells and dendritic cells. Although T cells can instruct
      dendritic cells to manifest tolerogenic properties after CTLA-4 engagement of B7,
      such a B7-mediated signaling is not known to occur in response to CD28. Here we
      show that mouse dendritic cells were induced by soluble CD28 to express
      interleukin 6 and interferon-gamma. Production of interleukin 6 required B7-1
      (CD80), B7-2 (CD86) and p38 mitogen-activated protein kinase and prevented
      interferon-gamma-driven expression of immunosuppressive tryptophan catabolism. In
      vivo, an adjuvant activity of soluble CD28 was demonstrated as enhanced T cell
      mediated immunity to tumor and self peptides and protection against microbial and
      tumor challenge. Thus, different ligands of B7 can signal dendritic cells to
      express functionally distinct effector responses.

PMID- 15467724
TI  - Domain-wall superconductivity in superconductor-ferromagnet hybrids.
AB  - Superconductivity and magnetism are two antagonistic cooperative phenomena, and
      the intriguing problem of their coexistence has been studied for several decades.
      Recently, artificial hybrid superconductor-ferromagnet systems have been commonly
      used as model systems to reveal the interplay between competing superconducting
      and magnetic order parameters, and to verify the existence of new physical
      phenomena, including the predicted domain-wall superconductivity (DWS). Here we
      report the experimental observation of DWS in superconductor-ferromagnet hybrids
      using a niobium film on a BaFe(12)O(19) single crystal. We found that the
      critical temperature T(c) of the superconductivity nucleation in niobium
      increases with increasing field until it reaches the saturation field of
      BaFe(12)O(19). In accordance with the field-shift of the maximum value of T(c),
      pronounced hysteresis effects have been found in resistive transitions. We argue
      that the compensation of the applied field by the stray fields of the magnetic
      domains as well as the change in the domain structure is responsible for the
      appearance of the DWS and the coexistence of superconductivity and magnetism in
      the superconductor-ferromagnet hybrids.

PMID- 15467725
TI  - Nanostructure engineering by templated self-assembly of block copolymers.
AB  - Self-assembling materials are the building blocks for bottom-up nanofabrication
      processes, but many self-assembled nanostructures contain defects and lack
      sufficient long-range order for certain nanotechnology applications. Here we
      investigate the formation of defects in a self-assembled array of spherical block
      copolymer microdomains, using topographical templates to control the local self
      assembly. Perfect ordered sphere arrays can form in both constant-width templates
      and width-modulated templates. For modulated templates, transition between
      configurations having a constant number of rows and configurations of stable
      arrays with varying numbers of rows is shown to be analogous to dislocation
      formation in an epitaxial thin film system. Based on the configuration transition
      energy and fluctuation energy, designed templates with a high tolerance for
      lithographical imperfections can direct precisely modulated block-copolymer
      nanostructures. This study provides insights into the design of hybrid systems
      combining top-down and bottom-up fabrication.

PMID- 15467726
TI  - TCR affinity and negative regulation limit autoimmunity.
AB  - Autoimmune diseases are often mediated by self-reactive T cells, which must be
      activated to cause immunopathology. One mechanism, known as molecular mimicry,
      proposes that self-reactive T cells may be activated by pathogens expressing
      crossreactive ligands. Here we have developed a model to investigate how the
      affinity of the T-cell receptor (TCR) for the activating agent influences
      autoimmunity. Our model shows that an approximately fivefold difference in the
      TCR affinity for the activating ligand results in a 50% reduction in the
      incidence of autoimmunity. A reduction in TCR-ligand affinity to approximately 20
      times lower than normal does not induce autoimmunity despite the unexpected
      induction of cytotoxic T lymphocytes (CTLs) and insulitis. Furthermore, in the
      absence of a key negative regulatory molecule, Cbl-b, 100% of mice develop
      autoimmunity upon infection with viruses encoding the lower-affinity ligand.
      Therefore, autoimmune disease is sensitive both to the affinity of the activating
      ligand and to normal mechanisms that negatively regulate the immune response.

PMID- 15467727
TI  - Intragenic DNA methylation alters chromatin structure and elongation efficiency
      in mammalian cells.
AB  - Transcriptional silencing in mammals is often associated with promoter
      methylation. However, a considerable number of genomic methylated CpGs exist in
      transposable elements, which are frequently found in intronic regions. To
      determine whether intragenic methylation influences transcription efficiency, we
      used the Cre/loxP-based system, RMCE, to introduce a transgene, methylated
      exclusively in a region downstream of the promoter, into a specific genomic site.
      This methylation pattern was maintained in vivo, and yielded a clear decrease in
      transgene expression relative to an unmethylated control. Notably, RNA polymerase
      II (Pol II) was depleted exclusively in the methylated region, as was histone H3
      di- and trimethylated on Lys4 and acetylated on Lys9 and Lys14. As the methylated
      region adopts a closed chromatin structure in vivo, we propose that dense
      intragenic DNA methylation in mammalian cells initiates formation of a chromatin
      structure that reduces the efficiency of Pol II elongation.

PMID- 15467728
TI  - PML bodies control the nuclear dynamics and function of the CHFR mitotic
      checkpoint protein.
AB  - Nuclear foci containing the promyelocytic leukemia protein (PML bodies), which
      occur in most cells, play a role in tumor suppression. Here, we demonstrate that
      CHFR, a mitotic checkpoint protein frequently inactivated in human cancers, is a
      dynamic component of PML bodies. Intermolecular fluorescence resonance energy
      transfer analysis identified a distinct fraction of CHFR that interacts with PML
      in living cells. This interaction modulates the nuclear distribution and mobility
      of CHFR. A trans-dominant mutant of CHFR that inhibits checkpoint function also
      prevents colocalization and interaction with PML. Conversely, the distribution
      and mobility of CHFR are perturbed in PML(-/-) cells, accompanied by aberrations
      in mitotic entry and the response to spindle depolymerization. Thus, PML bodies
      control the distribution, dynamics and function of CHFR. Our findings implicate
      the interaction between these tumor suppressors in a checkpoint response to
      microtubule poisons, an important class of anticancer drugs.

PMID- 15467729
TI  - Distinct transcriptional control and action of fibroblast growth factor receptor
      4 in differentiating skeletal muscle cells.
AB  - Although FGF signaling promotes myoblast proliferation and represses myogenic
      differentiation, one of the FGF receptors (FGFR), FGFR4, is expressed mainly in
      mature skeletal muscle. Disruption of FGFR4 signaling interrupts chick limb
      muscle formation. To determine the developmental regulation of FGFR4 expression,
      we compared the transcriptional control and action of FGFR4 in myoblasts and
      myotubes. We identified higher FGFR4 expression in differentiated myotubes than
      precursor myoblasts. FGFR4 promoter activity was localized within a region 115 bp
      upstream of the transcription start site. Overlapping fragments of this promoter
      displayed a distinct difference when compared by electromobility shift assay
      (EMSA) using nuclear extracts from myoblasts and myotubes. While fragments B (
      95/-56) and C (-65/-26) formed specific complexes in both cell types, these
      complexes were consistently more intense in myotubes than myoblasts. These
      complexes were efficiently competed by an Sp-type oligonucleotide and were
      supershifted by Sp1 and by Sp3 antibodies. Deletions of the Sp-binding sites in
      fragment B (-95/-56) confirmed their critical contribution to promoter activity.
      Moreover, Sp1 expression correlated with FGFR4-expression in myotubes. To
      determine whether FGFR4 expression regulates myoblast differentiation, we
      infected a soluble dominant-negative FGFR4-containing adenovirus into these
      cells. This significantly impeded Erk1/2 phosphorylation and differentiation of
      myoblasts into MHC-expressing myotubes. Our findings point to distinct
      transcriptional regulation and action for FGFR4 in differentiating skeletal
      muscle cells.

PMID- 15467730
TI  - CXCL12-CXCR4 interactions modulate prostate cancer cell migration,
      metalloproteinase expression and invasion.
AB  - The mechanisms responsible for prostate cancer metastasis are incompletely
      understood at both the cellular and molecular levels. In this regard, chemokines
      are a family of small, cytokine-like proteins that induce motility of neoplastic
      cells, leukocytes and cancer cells. The current study evaluates the molecular
      mechanisms of CXCL12 and CXCR4 in prostate cancer cell migration and invasion. We
      report that functional CXCR4 is significantly expressed by prostate cancer cell
      lines, LNCaP and PC3, when compared with normal prostatic epithelial cells
      (PrEC). As measured using motility and invasion chamber assays, prostate cancer
      cells migrated and invaded through extracellular matrix components in response to
      CXCL12, at rates that corresponded to CXCR4 expression. Anti-CXCR4 antibodies
      (Abs) significantly impaired the migration and invasive potential of PC3 and
      LNCaP cells. CXCL12 induction also enhanced collagenase-1 (metalloproteinase-1
      (MMP-1)) expression by LNCaP and PC3 cells. Collagenase-3 (MMP-13) was expressed
      by prostate cancer cells, but it was not expressed by PrEC cells or modulated by
      CXCL12. CXCL12 increased MMP-2 expression by LNCaP and PC3; however, MMP-9
      expression was elevated only in PC3 cells after CXCL12-CXCR4 ligation. PC3 cells
      also expressed high levels of stromelysin-1 (MMP-3) after CXCL12 stimulation.
      CXCL12 also significantly increased stromelysin-2 (MMP-10) expression by LNCaP
      cells. Stromelysin-3 (MMP-11) was expressed by LNCaP cells, but not by PC3 or
      PrEC cells and CXCL12 induced PC3 MMP-11 expression. Membrane type-1 MMP (MMP-14)
      was not expressed by PrEC or LNCaP cells, but CXCL12 significantly enhanced MMP
      14 expression by PC3 cells. These studies reveal important cellular and molecular
      mechanisms of CXCR4/CXCL12-mediated prostate cancer cell migration and invasion.

PMID- 15467731
TI  - SYT, a partner of SYT-SSX oncoprotein in synovial sarcomas, interacts with
      mSin3A, a component of histone deacetylase complex.
AB  - Synovial sarcomas are soft-tissue tumors predominantly affecting children and
      young adults. They are molecular-genetically characterized by the SYT-SSX fusion
      gene generated from chromosomal translocation t(X; 18) (p11.2; q11.2). When we
      screened new gene products that interact with SYT or SSX proteins by yeast two
      hybrid assay, we found that mSin3A, a component of the histone deacetylase
      complex, interacts with SYT but not with SSX. These results were confirmed by
      mammalian two-hybrid and pull-down assays. Analyses with sequential truncated
      proteins revealed a main mSin3A-interaction region on the SYT amino-terminal 93
      amino acids, and another one on the region between 187th amino acid and break
      point. In luciferase assay, mSin3A repressed the transcriptional activity of
      reporter promoter mediated by SYT and hBRM/BRG1. Our results suggest that the
      histone deacetylase complex containing mSin3A may regulate the transcriptional
      activation mediated by SYT.

PMID- 15467732
TI  - Involvement of overexpressed wild-type BRAF in the growth of malignant melanoma
      cell lines.
AB  - Comparative genomic hybridization (CGH) using 40 cell lines derived from
      malignant melanomas (MMs) revealed frequent amplification at 7q33-q34 containing
      BRAF gene, which often is mutated in MM. We found this gene to be amplified to a
      remarkable degree in the MM cell lines that exhibited high-level gains at 7q33
      q34 in CGH. Among 40 cell lines, the eight lines that revealed neither BRAF nor
      NRAS mutations showed even higher levels of BRAF mRNA expression than the 32
      mutated lines, although DNA amplification at 7q33-q34 was not detected in every
      lines overexpressing BRAF. MM cells that carried wild-type BRAF and NRAS showed
      constitutive overexpression of B-Raf protein and phosphorylation of extracellular
      signal-regulated kinase 1/2 (ERK1/2), even after serum starvation. Not only
      downregulation of the endogenously overexpressed wild-type B-Raf by antisense
      oligonucleotide but also a treatment with an inhibitor of mitogen-activated
      protein kinase kinase (MAPKK, MEK) reduced phosphorylated ERK1/2 and cell growth,
      whereas the exogenously expressed wild-type B-Raf promoted cell growth in MM
      cells. Our results provide the evidence that overexpression of wild-type B-Raf,
      in part but not always as a result of gene amplification, is one of the
      mechanisms underlying constitutive activation of the MAPK pathway that stimulates
      growth of MM cells.

PMID- 15467733
TI  - TMF/ARA160 is a BC-box-containing protein that mediates the degradation of Stat3.
AB  - TMF/ARA160 is a Golgi resident protein whose cellular functions have not been
      conclusively revealed. Herein we show that TMF/ARA160 can direct the proteasomal
      degradation of the key cell growth regulator - Stat3. TMF/ARA160 was dispersed in
      the cytoplasm of myogenic C2C12 cells that were grown under low-serum conditions.
      The cytoplasmic distribution of TMF/ARA160 was accompanied by its transient
      association with the tyrosine kinase Fer and with Stat3, which underwent
      proteasomal degradation under those conditions. Moreover, serum deprivation
      induced the association of ubiquitinated proteins, with the TMF/ARA160 complex.
      However, TMF/ARA160 did not bind Stat1, whose cellular levels were increased in
      serum-starved C2C12 cells. Amino-acid sequence analysis identified a BC-box
      element in TMF/ARA160 that mediated the binding of this protein to elongin C.
      Ectopic expression of TMF/ARA160 in serum-starved C2C12 cells drove the
      ubiquitination and proteasomal degradation of Stat3, an effect that was not
      caused by TMF/ARA160 devoid of the BC-box motif. Thus, the Golgi apparatus
      harbors a novel BC-box-containing protein that can direct Stat3 to proteasomal
      degradation. Interestingly, the level of TMF/ARA160 was significantly decreased
      in malignant brain tumors, implying a suppressive role of that protein in tumor
      progression.

PMID- 15467734
TI  - Epigenetic inactivation of class II transactivator (CIITA) is associated with the
      absence of interferon-gamma-induced HLA-DR expression in colorectal and gastric
      cancer cells.
AB  - Tightly regulated at the level of transcription, expression of MHC class II
      molecules varies significantly among gastrointestinal cancers. High levels of MHC
      class II expression are often associated with a better prognosis, which is
      indicative of the involvement of CD4+ lymphocytes in tumor suppression, but the
      molecular mechanism by which MHC class II expression is regulated remains
      unclear. In the present study, we investigated the expression of one inducible
      MHC class II molecule, HLA-DR, and its coactivators in a panel of colorectal and
      gastric cancer cell lines. Interferon-gamma induced expression of HLA-DR in 14 of
      20 cell lines tested; the remaining six cell lines did not express HLA-DR.
      Analysis of the expression of transcription factors and coactivators associated
      with HLA-DR revealed that the loss of CIITA expression was closely associated
      with the absence of HLA-DR induction. Moreover, DNA methylation of the 5' CpG
      island of CIITA-PIV was detected in all cancer cells that lacked CIITA. The
      methylation and resultant silencing of CIITA-PIV depended on the activities of
      two DNA methyltransferases, DNMT1 and DNMT3B, and their genetic inactivation
      restored CIITA-PIV expression. It thus appears that CIITA methylation is a key
      mechanism that enables some gastrointestinal cancer cells to escape immune
      surveillance.

PMID- 15467735
TI  - HES-1 inhibits 17beta-estradiol and heregulin-beta1-mediated upregulation of E2F
      1.
AB  - We have previously shown that expression of the transcription factor HES-1 is
      required for the growth-inhibitory effect of all-trans retinoic acid on MCF-7
      cells. In this study, we have used T47D cells with tetracyclin-regulated
      expression of wild-type or a dominant-negative form of HES-1. Expression of HES-1
      in T47D cells inhibited G1/S-phase transition and activation of Cdk2 elicited by
      estrogen. Estrogen treatment of T47D cells caused increased expression of E2F-1,
      and this expression was inhibited by cotreatment with all-trans retinoic acid. We
      show that the effect is mediated through HES-1, which directly downregulates E2F
      1 expression through a CACGAG-site within the E2F-1 promoter. Furthermore,
      proliferation caused by heregulin-beta1 treatment of T47D cells was inhibited by
      all-trans retinoic acid and this effect was mediated by HES-1. Interestingly,
      heregulin-beta1-mediated upregulation of E2F-1 expression was directly inhibited
      by HES-1 through the same CACGAG-site as seen with estrogen-stimulated induction.
      In addition, we found that two important downstream target genes of estrogen and
      heregulin-beta1 that are regulated through E2F-1, cyclin E and NPAT, were both
      regulated in a similar fashion by all-trans retinoic acid, and these effects were
      antagonized by dominant-negative HES-1. These findings establish that HES-1
      inhibits both estrogen- and heregulin-beta1-stimulated growth of breast cancer
      cells, and further suggest that growth inhibition induced in these cells by all
      trans retinoic acid occurs via HES-1-mediated downregulation of E2F-1 expression.

PMID- 15467736
TI  - HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia
      associated protein PLZF.
AB  - PLZF, the promyelocytic leukaemia zinc-finger protein, is a transcriptional
      repressor essential to development. In some acute leukaemias, a chromosomal
      translocation fusing the PLZF gene to that encoding the retinoic acid receptor
      RARalpha gives rise to a fusion protein, PLZF-RARalpha, thought to be responsible
      for constitutive repression of differentiation-associated genes in these cells.
      Repression by both PLZF and PLZF-RARalpha is sensitive to the histone deacetylase
      inhibitor TSA, and PLZF was previously shown to interact physically with HDAC1, a
      class I histone deacetylase. We here asked whether class II histone deacetylases,
      known to be generally involved in differentiation processes, participate in the
      repression mediated by PLZF and PLZF-RARalpha, and found that PLZF interacts with
      HDAC4 in both GST-pull-down and co-immunoprecipitation assays. Furthermore, HDAC4
      is indeed involved in PLZF and PLZF-RARalpha-mediated repression, since an
      enzymatically dead mutant of HDAC4 released the repression, as did an siRNA that
      blocks HDAC4 expression. Taken together, our data indicate that recruitment of
      HDAC4 is necessary for PLZF-mediated repression in both normal and leukaemic
      cells.

PMID- 15467737
TI  - Unliganded thyroid hormone receptor beta1 inhibits proliferation of murine
      fibroblasts by delaying the onset of the G1 cell-cycle signals.
AB  - Thyroid hormone receptors (TRs) are members of the ligand-inducible transcription
      factor superfamily. The two major functional TRs (alpha1 and beta1) have
      different spatial and temporal expression patterns and specific physiological
      functions for these isoforms are now starting to emerge. By expressing these TR
      isoforms individually in Swiss 3T3 fibroblasts, we found that TRbeta1 expression,
      in the absence of hormone, provokes a proliferation arrest in G0/G1, lengthening
      the cycling time. Upon serum stimulation TRbeta1-expressing cells showed a marked
      delay in the induction of cyclins D and E, in the phosphorylation of
      retinoblastoma protein, and in the activation of cyclin-dependent kinase 2,
      accompanied by increased levels of cyclin-dependent kinase inhibitor p27Kip1.
      Accordingly, serum-stimulated E2F-1 transcriptional activity was repressed by
      TRbeta1 in transient transfection experiments. Analysis of the receptor domains
      required for this effect confirmed that there is no need for a functional ligand
      binding domain while the DNA-binding domain is essential. In this work, we
      demonstrate for the first time that TRbeta1 participates in the molecular
      mechanisms that control cell proliferation. The unliganded TRbeta1 impairs the
      normal induction of the G1/S cycle regulators preventing progression into the S
      phase.

PMID- 15467738
TI  - Interferon-regulatory factor-1 is critical for tamoxifen-mediated apoptosis in
      human mammary epithelial cells.
AB  - Unlike estrogen receptor-positive (ER(+)) breast cancers, normal human mammary
      epithelial cells (HMECs) typically express low nuclear levels of ER (ER poor). We
      previously demonstrated that 1.0 microM tamoxifen (Tam) promotes apoptosis in
      acutely damaged ER-poor HMECs through a rapid, 'nonclassic' signaling pathway.
      Interferon-regulatory factor-1 (IRF-1), a target of signal transducer and
      activator of transcription-1 transcriptional regulation, has been shown to
      promote apoptosis following DNA damage. Here we show that 1.0 microM Tam promotes
      apoptosis in acutely damaged ER-poor HMECs through IRF-1 induction and caspase
      1/3 activation. Treatment of acutely damaged HMEC-E6 cells with 1.0 microM Tam
      resulted in recruitment of CBP to the gamma-IFN-activated sequence element of the
      IRF-1 promoter, induction of IRF-1, and sequential activation of caspase-1 and 
      3. The effects of Tam were blocked by expression of siRNA directed against IRF-1
      and caspase-1 inhibitors. These data indicate that Tam induces apoptosis in HMEC
      E6 cells through a novel IRF-1-mediated signaling pathway that results in
      activated caspase-1 and -3.

PMID- 15467739
TI  - Inactivating mutations of the Siah-1 gene in gastric cancer.
AB  - SIAH-1: is the mammalian homolog of Drosophila seven in absentia (sina) and has
      been identified as a p53-inducible gene. Siah-1 can induce cell cycle arrests,
      tumor suppression, and apoptosis through a novel beta-catenin degradation
      pathway. To determine whether genetic alterations of Siah-1 gene are involved in
      the development and/or progression of gastric cancer, we searched for mutation of
      the Siah-1 gene in 95 gastric cancers by single-strand conformational
      polymorphism and sequencing. The effect of Siah-1 on beta-catenin degradation was
      further examined in wild- and mutant-type Siah-1-transfected HEK 293T cells. We
      found two missense mutations of the Siah-1 gene. The cases with Siah-1 mutation
      showed nuclear translocation and cytoplasmic staining of beta-catenin.
      Interestingly, two mutants of Siah-1 stabilized cytoplasmic levels of beta
      catenin, even after treatment of adriamycin. Furthermore, both mutants failed to
      suppress cyclin D1 expression and to induce apoptosis. These data suggest that
      inactivating mutations of the Siah-1 may contribute to the development of gastric
      cancer through beta-catenin stabilization and apoptosis block.

PMID- 15467740
TI  - Beta-parvin inhibits integrin-linked kinase signaling and is downregulated in
      breast cancer.
AB  - We analysed breast tumors and breast cancer cell lines for the expression of beta
      parvin (ParvB), an adaptor protein that binds to the integrin-linked kinase
      (ILK). Quantitative RT-PCR indicated that ParvB mRNA was downregulated, by at
      least 60%, in four of nine breast tumors, relative to patient-matched normal
      mammary gland tissue. We also found that ParvB protein levels were reduced by >
      or =90% in five of seven advanced tumors, relative to matched normal breast
      tissue. Conversely, ILK protein and kinase activity levels were elevated in these
      tumors, suggesting that downregulation of ParvB stimulates ILK signaling. Western
      blot analyses indicated very low levels of ParvB protein in MDA-MB-231 and MCF7
      breast cancer cells, facilitating functional studies of the effects of ParvB on
      ILK signaling. Expression of ParvB in MDA-MB-231 and MCF7 cells increased cell
      adhesion to collagen. ParvB inhibited ILK kinase activity, anchorage-independent
      cell growth and in vitro matrigel invasion by MDA-MB-231 cells. EGF-induced
      phosphorylation of two ILK targets, PKB (Ser473) and glycogen synthase kinase
      3beta (Ser9), was also inhibited by ParvB. These results indicated that ParvB
      inhibits ILK signaling downstream of receptor tyrosine kinases. Our results
      suggest that loss of ParvB expression is a novel mechanism for upregulating ILK
      activity in tumors.

PMID- 15467741
TI  - Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor
      merlin and Grb2.
AB  - Neurofibromatosis 2 (NF2) is a dominantly inherited disorder characterized by
      bilateral vestibular schwannomas and meningiomas. Merlin, the neurofibromatosis 2
      tumor suppressor protein, is related to the ERM (ezrin, radixin, moesin) proteins
      and, like its family members, is thought to play a role in plasma membrane
      cytoskeletal interactions. We report a novel protein as a merlin-specific binding
      partner that we have named magicin (merlin and Grb2 interacting cytoskeletal
      protein) and show that the two proteins interact in vitro and in vivo as well as
      colocalize beneath the plasma membrane. Magicin is a 24 kDa protein that is
      expressed in many cell lines and tissues. Magicin, similar to merlin, associates
      with the actin cytoskeleton as determined by cofractionation, immunofluorescence
      and electron microscopy. Analysis of the magicin sequence reveals binding motifs
      for the adaptor protein Grb2. Employing affinity binding, blot overlay and co
      immunoprecipitation assays, we demonstrate an interaction between Grb2 and
      magicin. In addition, merlin is capable of forming a ternary complex with magicin
      and Grb2. These results support a role for merlin in receptor-mediated signaling
      at the cell surface, and may have implications in the regulation of cytoskeletal
      reorganization.

PMID- 15467742
TI  - Transcriptional repression of MMP-1 by p21SNFT and reduced in vitro invasiveness
      of hepatocarcinoma cells.
AB  - p21SNFT (21 kDa small nuclear factor isolated from T cells) is a human basic
      leucine zipper transcription factor that can repress AP-1-mediated transcription.
      We show here that overexpression of p21SNFT in HepG2 cells leads to repression of
      matrix metalloproteinase-1 by 70-80%. p21SNFT interacted with Jun at the matrix
      metalloproteinase-1 promoter -88 Ets/AP-1 enhancer element, where Jun is known to
      activate transcription via interaction with Fos and Ets proteins. When
      p21SNFT/Jun dimers bound the element in the presence of Ets, DNA was protected
      differently than when Fos was paired with Jun. The data suggest a difference in
      overall conformation between p21SNFT-containing and Fos-containing complexes that
      may be involved in the repression of matrix metalloproteinase-1 by p21SNFT.
      Overexpression of p21SNFT led to a reduction in invasiveness of HepG2 cells
      through type I collagen and reconstituted basement membrane, an effect similar to
      that obtained via direct immunodepletion of matrix metalloproteinase-1. The
      results indicate that the mechanism of repression of matrix metalloproteinase-1
      by p21SNFT may be exploited in inhibiting pathological matrix remodeling during
      cancer progression in vivo.

PMID- 15467743
TI  - Mxi1-SRalpha: a novel Mxi1 isoform with enhanced transcriptional repression
      potential.
AB  - Mxi1 belongs to the Myc/Max/Mad network of proteins that have been implicated in
      the control of multiple aspects of cellular behavior. Previously, we had reported
      that the mouse mxi1 gene gives rise to two distinct transcript forms that can
      encode proteins with dramatically different functional abilities. The Mxi1-SR
      protein (here termed Mxi1-SRbeta) can interact with Sin3/histone deacetylase and
      function as a potent transcriptional repressor and growth suppressor, while the
      Mxi1-WR protein lacks these activities. Here, we describe a new mxi1-derived
      transcript form (termed mxi1-SRalpha) whose expression is governed by its own
      promoter, resulting in a spatiotemporally distinct expression profile from that
      of the highly related mxi1-SRbeta form. Moreover, the Mxi1-SRalpha protein
      product, with its unique Sin3 interacting domain, has a greater affinity than its
      Mxi1-SRbeta counterpart for the Sin3 adapter proteins as well as an enhanced
      potential for transcriptional repression in transient reporter assays. Our
      identification of this novel Mxi1 isoform that results from alternative 5' exon
      usage adds an additional layer of complexity to the Mad/Mxi1 family. In addition,
      our findings warrant re-evaluation of mxi1 expression patterns on the cellular
      level and its status in human cancer samples, with a renewed focus on the
      distinct isoforms.

PMID- 15467744
TI  - Fibronectin and type IV collagen activate ERalpha AF-1 by c-Src pathway: effect
      on breast cancer cell motility.
AB  - The expression of estrogen receptor alpha (ERalpha) is generally associated with
      a less invasive and aggressive phenotype in breast carcinoma. In an attempt to
      understand the role of ERalpha in regulating breast cancer cells invasiveness, we
      have demonstrated that cell adhesion on fibronectin (Fn) and type IV Collagen
      (Col) induces ERalpha-mediated transcription and reduces cell migration in MCF-7
      and in MDA-MB-231 cell lines expressing ERalpha. Analysis of deleted mutants of
      ERalpha indicates that the transcriptional activation function (AF)-1 is required
      for ERalpha-mediated transcription as well as for the inhibition of cell
      migration induced by cell adhesion on extracellular matrix (ECM) proteins. In
      addition, the nuclear localization signal region and some serine residues in the
      AF-1 of the ERalpha are both required for the regulation of cell invasiveness as
      we have observed in HeLa cells. It is worth noting that c-Src activation is
      coincident with adhesion of cells to ECM proteins and that the inhibition of c
      Src activity by PP2 or the expression of a dominant-negative c-Src abolishes
      ERalpha-mediated transcription and partially reverts the inhibition of cell
      invasiveness in ERalpha-positive cancer cells. These findings address the
      integrated role of ECM proteins and ERalpha in influencing breast cancer cell
      motility through a mechanism that involves c-Src and seems not to be related to a
      specific cell type.

PMID- 15467745
TI  - The small G-protein RalA stimulates metastasis of transformed cells.
AB  - RAS oncogenes play a critical role in oncogenic transformation and metastases
      formation. Here we show that Ha-ras greatly stimulates spontaneous metastatic
      activity of transformed cells through the Ras/RalGDS/RalA intracellular signaling
      pathway. Introduction of RalA alone leads to a drastic increase of metastatic
      activity of transformed cells. We demonstrate that metastatic ability of cells
      could be dramatically enhanced by RalA stimulation or, conversely, hampered by
      RalA suppression. Furthermore, we found that during in vivo selection cells
      acquire high metastatic properties as a result of endogenous RalA activation. The
      ability of RalA to induce metastasis was demonstrated in spontaneously
      transformed as well as in virus transformed fibroblasts.

PMID- 15467746
TI  - Prediction of high risk Ewing's sarcoma by gene expression profiling.
AB  - Ewing's sarcoma (ES) is the second most common primary malignant bone tumor in
      children and adolescents. Currently accepted clinical prognostic factors fail to
      classify ES patients' risk to relapse at diagnosis. We aimed to find a new
      strategy to distinguish between poor and good prognosis ES patients already at
      diagnosis. We analysed the gene expression profiles of 14 primary tumor specimens
      and six metastases from ES patients, using oligonucleotide microarray analysis.
      The over-expression of two genes was validated by quantitative PCR using the
      LightCycler system. We identified two distinct gene expression signatures
      distinguishing high-risk ES patients that are likely to progress from low-risk ES
      patients with a favorable prognosis of long-term progression-free survival. The
      microarray-based classification was superior to currently used prognostic
      parameters. Over-expressed genes in the poor prognosis patients included genes
      regulating the cell cycle and genes associated with invasion and metastasis,
      while among the downregulated genes were tumor suppressor genes and inducers of
      apoptosis. Our results indicate the existence of a specific gene expression
      signature of outcome in ES already at diagnosis, and provide a strategy to select
      patients who would benefit from risk-adapted improved therapy.

PMID- 15467747
TI  - The Kaposi's sarcoma-associated herpesvirus K-bZIP protein represses transforming
      growth factor beta signaling through interaction with CREB-binding protein.
AB  - Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is involved in the
      pathogenesis of KS, primary effusion lymphoma, and multicentric Castleman's
      disease. K-bZIP, the protein encoded by the open reading frame K8 of KSHV, is a
      member of the basic region-leucine zipper family of transcription factors. We
      studied the mechanisms that underlie KSHV-induced oncogenesis by investigating
      whether K-bZIP perturbs signaling through transforming growth factor beta (TGF
      beta), which inhibits proliferation of a wide range of cell types. K-bZIP
      repressed TGF-beta-induced, Smad-mediated transcriptional activity and
      antagonized the growth-inhibitory effects of TGF-beta. Since both K-bZIP and Smad
      are known to interact with CREB-binding protein (CBP), the effect of CBP on
      inhibition of Smad-mediated transcriptional activation by K-bZIP was examined. K
      bZIP mutants, which lacked the CBP-binding site, could not repress TGF-beta
      induced or Smad3-mediated transcriptional activity. Overexpression of CBP
      restored K-bZIP-induced inhibition of Smad3-mediated transcriptional activity.
      Competitive interaction studies showed that K-bZIP inhibited the interaction of
      Smad3 with CBP. These results suggest that K-bZIP, through its binding to CBP,
      disrupts TGF-beta signaling by interfering with the recruitment of CBP into
      transcription initiation complexes on TGF-beta-responsive elements. We propose a
      possibility that K-bZIP may contribute to oncogenesis through its ability to
      promote cell survival by repressing TGF-beta signaling.

PMID- 15467748
TI  - Loss of one allele of ARF rescues Mdm2 haploinsufficiency effects on apoptosis
      and lymphoma development.
AB  - The tumor suppressor p19ARF inhibits Mdm2, which restricts the activity of p53.
      Complicated feedback and control mechanisms regulate ARF, Mdm2, and p53
      interactions. Here we report that ARF haploinsufficiency completely rescued the
      p53-dependent effects of Mdm2 haploinsufficiency on B-cell development, survival,
      and transformation. In contrast to Mdm2+/- B cells, Mdm2+/- B cells deficient in
      ARF were similar to wild-type B cells in their rates of growth and apoptosis and
      activation of p53. Consequently, the profoundly reduced numbers of B cells in
      Mdm2+/-Emu-myc transgenic mice were restored to normal levels in ARF+/-Mdm2+/-Emu
      myc transgenics. Additionally, ARF+/-Mdm2+/-Emu-myc transgenics developed
      lymphomas at rates analogous to those observed for wild-type Emu-myc transgenics,
      demonstrating that loss of one allele of ARF rescued the protracted lymphoma
      latency in Mdm2+/-Emu-myc transgenics. Importantly, in ARF+/-Mdm2+/-Emu-myc
      transgenic lymphomas, p53 was inactivated at the frequency observed in lymphomas
      of wild-type Emu-myc transgenics. Collectively, these results support a model
      whereby the stoichiometry of Mdm2 and ARF controls apoptosis and tumor
      development, which should have significant implications in the treatment of
      malignancies that have inactivated ARF.

PMID- 15467749
TI  - The human protein Hugl-1 substitutes for Drosophila lethal giant larvae tumour
      suppressor function in vivo.
AB  - Drosophila lethal giant larvae: (lgl), discs large (dlg) and scribble (scrib) are
      tumour suppressor genes acting in a common pathway, whose loss of function leads
      to disruption of cell polarity and tissue architecture, uncontrolled
      proliferation and growth of neoplastic lesions. Mammalian homologues of these
      genes are highly conserved and evidence is emerging concerning their role in cell
      proliferation control and tumorigenesis in humans. Here we investigate the
      functional conservation between Drosophila lethal giant larvae and its human
      homologue Hugl-1(Llgl1). We first show that Hugl-1 is lost in human solid
      malignancies, supporting its role as a tumour suppressor in humans. Hugl-1
      expression in homozygous lgl Drosophila mutants is able to rescue larval
      lethality; imaginal tissues do not show any neoplastic features, with Dlg and
      Scrib exhibiting the correct localization; animals undergo a complete
      metamorphosis and hatch as viable adults. These data demonstrate that Hugl-1 can
      act as a tumour suppressor in Drosophila and thus is the functional homologue of
      lgl. Furthermore, our data suggest that the genetic pathway including the tumour
      suppressors lgl, dlg and scrib may be conserved in mammals, since human scrib and
      mammalian dlg can also rescue their respective Drosophila mutations. Our results
      highlight the usefulness of fruit fly as a model system for investigating in vivo
      the mechanisms linking loss of cell polarity and cell proliferation control in
      human cancers.

PMID- 15467750
TI  - A RasGAP-derived cell permeable peptide potently enhances genotoxin-induced
      cytotoxicity in tumor cells.
AB  - Treatment of many cancers relies on the combined action of several genotoxins,
      but the detrimental effect of these drugs on normal cells can cause severe side
      effects. One major challenge in anticancer therapy is therefore to increase the
      selectivity of current treatments toward cancer cells in order to spare normal
      cells. We have recently demonstrated that a RasGAP caspase cleavage fragment is
      able to sensitize HeLa cells towards cisplatin-induced apoptosis. Here, we extend
      this observation by showing that this fragment also enhances cell death induced
      by adriamycin and mitoxantrone, two other widely used genotoxins. Furthermore, we
      have delineated a short sequence within this fragment that still bears the
      genotoxin-sensitization property. The peptide encoded by this sequence, when
      fused to the TAT cell permeation sequence, potently sensitized a number of tumors
      cells, but not normal cells, towards apoptosis induced by cisplatin, adriamycin
      and mitoxantrone. This sensitization effect was not mediated through modulation
      of NFkappaB activity or activation of the JNK and p38 MAPK pathways. Our results
      demonstrate the feasibility in enhancing the efficacy of currently used drugs to
      selectively kill cancer cells using peptides derived from pro-apoptotic caspase
      substrate fragments.

PMID- 15467751
TI  - Differential regulation of expression of the mammalian DNA repair genes by growth
      stimulation.
AB  - During DNA replication, DNA becomes more vulnerable to certain DNA damages. DNA
      repair genes involved in repair of the damages may be induced by growth
      stimulation. However, regulation of DNA repair genes by growth stimulation has
      not been analysed in detail. In this report, we analysed the regulation of
      expression of mammalian MSH2, MSH3 and MLH1 genes involved in mismatch repair,
      and Rad51 and Rad50 genes involved in homologous recombination repair, in
      relation to cell growth. Unexpectedly, we found a clear difference in regulation
      of these repair gene expression by growth stimulation even in the same repair
      system. The expression of MSH2, MLH1 and Rad51 genes was clearly growth
      regulated, whereas MSH3 and Rad50 genes were constitutively expressed, suggesting
      differential requirement of the repair gene products for cell proliferation. MSH3
      gene is located in a bidirectionally divergent manner with DHFR gene that is
      regulated by growth stimulation, indicating that bidirectionally divergent
      promoters are not necessarily coordinately regulated. Promoter analysis showed
      that the growth-regulated expression of MLH1 and Rad51 genes was mainly mediated
      by E2F that plays crucial roles in regulation of DNA replication, suggesting
      close relation between some of the repair genes and DNA replication.

PMID- 15467752
TI  - Multidomain Bcl-2 homolog Bax but not Bak mediates synergistic induction of
      apoptosis by TRAIL and 5-FU through the mitochondrial apoptosis pathway.
AB  - The death ligand TRAIL synergizes with DNA-damaging therapies such as
      chemotherapeutic drugs or ionizing irradiation. Here, we show that the synergism
      of TRAIL and 5-fluorouracil (5-FU) and cross-sensitization between TRAIL and 5-FU
      for induction of apoptosis, entirely depend on Bax proficiency in human DU145 and
      HCT116 carcinoma cells. DU145 prostate carcinoma cells that have lost Bax protein
      expression due to mutation fail to release cytochrome c and to activate caspase-3
      and -9 when exposed to TRAIL and 5-FU. In contrast, TRAIL sensitized for 5-FU
      induced apoptosis and vice versa upon reconstitution of Bax expression.
      Isobolographic analyses of ED50 doses for 5-FU at increasing TRAIL concentrations
      showed a clear synergism of TRAIL and 5-FU in Bax-expressing cells. In contrast,
      the effect was merely additive in DU145 cells lacking Bax. Notably, both DU145
      and HCT116 Bax-deficient cells still express Bak. This indicates that Bak is not
      sufficient to mediate cross-sensitization and synergism between 5-FU and TRAIL.
      Stable overexpression of Bak in DU145 sensitized for epirubicin-induced apoptosis
      but failed to confer synergy between TRAIL and 5-FU. Moreover, we show by the use
      of EGFP-tagged Bax and Bak that TRAIL and 5-FU synergistically trigger
      oligomerization and clustering of Bax but not Bak. These data clearly establish
      distinct roles for Bax and Bak in linking the TRAIL death receptor pathway to the
      mitochondrial apoptosis signaling cascade and delineate a higher degree of
      specificity in signaling for cell death by multidomain Bcl-2 homologs.

PMID- 15467753
TI  - NHERF (Na+/H+ exchanger regulatory factor) gene mutations in human breast cancer.
AB  - Yeast two-hybrid screening was used to explore novel proteins that interact with
      a breast tumor or metastasis suppressor, SYK (spleen tyrosine kinase). The
      screening yielded NHERF (Na+/H+ exchanger regulatory factor, also known as NHERF1
      or EBP-50) that binds to the interdomain B of SYK. NHERF is an estrogen
      responsive gene that encodes an inhibitory factor for epithelial Na+/H+ exchanger
      isoform 3 (NHE3). We found intragenic mutation of the NHERF gene accompanied by
      loss of heterzygosity (LOH) in approximately 3% (3/85) of breast cancer cell
      lines and primary breast tumors. Mutations occurred at the conserved PDZ domains
      at NHERF NH2-terminus that bound to SYK, or at its COOH-terminus motif that binds
      to MERLIN, the product of Neurofibromatosis 2 (NF2) tumor suppressor gene. NHERF
      tumorigenic mutations decreased or abolished its interaction with SYK or MERLIN,
      suggesting a pathway link among these three molecules that may play a critical
      role in mammary neoplastic progression. Primary breast tumors with LOH at the
      NHERF locus had clinical presentations of higher aggressiveness, indicating that
      deregulated NHERF signaling may be associated with disease progression. Moreover,
      the LOH was inversely correlated with SYK promoter methylation, suggesting that
      NHERF and SYK may transduce a common suppressive signal. Taken together, the
      results indicated NHERF to be a candidate tumor suppressor gene in human breast
      carcinoma that may be interconnected to the SYK and MERLIN suppressors.

PMID- 15467754
TI  - E-cadherin mutation and Snail overexpression as alternative mechanisms of E
      cadherin inactivation in synovial sarcoma.
AB  - We have recently reported frequent E-cadherin gene mutations in synovial sarcoma
      (SS), suggesting mutational inactivation of E-cadherin as a potential mechanism
      of spindle cell morphology in SS, a spindle cell sarcoma that shows areas of
      glandular epithelial differentiaton in some cases (biphasic SS) and only pure
      spindle cell morphology in most cases (monophasic SS). However, the mechanism of
      downregulation of E-cadherin in SS remains unknown. To further address this
      issue, we analysed the mechanisms of E-cadherin silencing in 40 SS. Genetic and
      epigenetic changes in the E-cadherin gene, and the expression level of its
      transcriptional repressor Snail were examined by polymerase chain reaction-single
      strand conformation polymorphism (PCR-SSCP), methylation-specific PCR, and real
      time quantitative PCR, respectively. Expression of E-cadherin was examined by RT
      PCR and immunohistochemistry. We also examined ELF3, a transcription factor
      associated with epithelial differentiation in SS in a previous cDNA microarray,
      by RT-PCR. E-cadherin and ELF3 transcripts were detected, respectively, in 27/40
      (67.5%) and in 25/40 (62.5%) of SS, and these epithelial-related genes were
      almost always coexpressed. Hypermethylation of the promoter of the E-cadherin
      gene was detected in five cases (12.5%) in SS; however, E-cadherin was silenced
      at mRNA level in only one of the five cases. E-cadherin missense mutations were
      observed in five cases (12.5%) of SS. In SS, all five cases with E-cadherin
      missense mutations had the SYT-SSX1 fusion and were monophasic tumors, suggesting
      a relationship between the SYT-SSX fusion type and E-cadherin missense mutation
      (P=0.07). E-cadherin mRNA expression in SS was associated with reduced Snail
      expression level (P=0.03). E-cadherin membranous expression was observed in 14/40
      (35.0%) of SS, and was also correlated with SYT-SSX1 fusion type and biphasic
      histology. ELF3 was confirmed to be more highly expressed in biphasic than
      monophasic SS by real-time quantitative PCR. These results suggest that in SS the
      loss of E-cadherin expression occurs either by Snail trans-repression or by
      inactivating mutations. Thus, E-cadherin downregulation is associated with the
      loss or absence of glandular epithelial differentiation in certain SS.

PMID- 15467755
TI  - Destabilization of vascular endothelial growth factor mRNA by the zinc-finger
      protein TIS11b.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic cytokine, which plays
      a major role in tumor angiogenesis. VEGF mRNA expression is controlled by
      hypoxia, growth factors and hormones through both transcriptional and post
      transcriptional mechanisms. VEGF mRNA has a short half-life and its abundance is
      regulated by the binding of stabilizing (HuR, hRNP-L) and still uncharacterised
      destabilizing proteins to its 3'-untranslated region. Here, we report that the
      ACTH-regulated zinc-finger protein TIS11b and its homologs TIS11 and TIS11d
      interact with the 3'-untranslated region of VEGF mRNA and decrease its stability
      (half-life reduced from 130 to 60 min). Within the 2201 bp 3'-untranslated region
      of VEGF mRNA, we identified a 75 bp domain, containing two consensus AU-rich
      motifs, which binds TIS11b and mediates its destabilizing activity.
      Ribonucleoprotein (RNP) complex immunoprecipitation experiments allowed us to
      demonstrate that the interaction between TIS11b and VEGF 3'-untranslated region
      occurs in live cells. Knocking down TIS11b expression in primary adrenocortical
      cells with small interfering (si)RNAs clearly indicated that TIS11b participates
      in the control of both basal and, to a larger extent, ACTH-induced VEGF mRNA
      expression levels. TIS11b is the first VEGF mRNA-destabilizing protein identified
      so far and therefore appears as a new potential target in antiangiogenic
      therapies.

PMID- 15467756
TI  - The PI 3-kinase/Akt signaling pathway is activated due to aberrant Pten
      expression and targets transcription factors NF-kappaB and c-Myc in pancreatic
      cancer cells.
AB  - The persistent activation of signaling cascades results in dramatic consequences
      that include loss of cellular growth control and neoplastic transformation. We
      show here that phosphoinositide 3-kinase (PI 3-kinase) and its mediator Akt were
      constitutively activated in pancreatic cancer and that this might be due to the
      aberrant expression of their natural antagonist MMAC/PTEN. Indeed, our results
      show that MMAC/PTEN expression was either lost or significantly reduced in five
      of eight cell lines and in twelve of seventeen tumor specimens examined. That the
      poor expression of MMAC/PTEN in pancreatic cancer cells could be due to promoter
      methylation was indicated by methylation-specific PCR analysis. Our studies also
      indicated that PI 3-kinase targeted two important transcription factors in
      pancreatic cancer cells. The ability of constitutively activated NF-kappaB to
      induce gene expression and the stabilization of c-MYC protein by decreased
      phosphorylation of Thr58 were both dependent on PI 3-kinase activity. When
      pancreatic cancer cells were treated with a peptide antagonist of NF-kappaB
      nuclear translocation, or stably transfected with a dominant-negative mutant of
      MYC, their proliferation was markedly inhibited. Taken together, these data
      indicate that the aberrant expression of MMAC/PTEN contributes to the activation
      of the PI 3-kinase/Akt pathway and its transcription factor mediators in
      pancreatic cancer.

PMID- 15467757
TI  - Integrin signaling links protein kinase Cepsilon to the protein kinase B/Akt
      survival pathway in recurrent prostate cancer cells.
AB  - Failure of hormone therapy often involves an outgrowth of protein kinase Cepsilon
      (PKCepsilon)-positive cells in recurrent prostate cancer. Our previous
      investigations have uncovered evidence of a complex signaling network operating
      downstream of this oncogenic protein kinase to actively advance the survival and
      proliferation of prostate cancer cells. In this study, we present evidence of a
      functional interplay among integrin receptors, PKCepsilon, and protein kinase B
      (PKB/Akt) in recurrent CWR-R1 prostate cancer cells. Flow cytometry and confocal
      microscopy provided evidence that PKCepsilon signaling promoted the assembly of
      matrix adhesions containing an abundance of colocalized actin filaments and beta1
      integrins that exhibited an exposed activation epitope on the surface of live CWR
      R1 cells. Reciprocal coimmunoprecipitations provided evidence of signaling
      complexes containing PKCepsilon, beta1 integrins, Src, and PKB/Akt in CWR-R1 cell
      cultures. An investigation into the functional significance of these
      interactions, and of their positive influence on beta1 integrins, demonstrated
      that PKCepsilon and several key components of the PKB/Akt signaling pathway
      remain constitutively phosphorylated/activated in adherent but not suspension
      cultures of PTEN-positive CWR-R1 cells. Gene transfer, antisense and
      pharmacological experiments provided additional support for the hypothesis that a
      mutually reinforcing signaling loop sustains the activation of beta1 integrins,
      PKCepsilon, and PKB/Akt in adherent prostate cancer cells.

PMID- 15467758
TI  - Human SNM1B is required for normal cellular response to both DNA interstrand
      crosslink-inducing agents and ionizing radiation.
AB  - DNA interstrand crosslinks (ICLs) are critical lesions for the mammalian cell
      since they affect both DNA strands and block transcription and replication. The
      repair of ICLs in the mammalian cell involves components of different repair
      pathways such as nucleotide-excision repair and the double-strand
      break/homologous recombination repair pathways. However, the mechanistic details
      of mammalian ICL repair have not been fully delineated. We describe here the
      complete coding sequence and the genomic organization of hSNM1B, one of at least
      three human homologs of the Saccharomyces cerevisiae PSO2 gene. Depletion of
      hSNM1B by RNA interference rendered cells hypersensitive to ICL-inducing agents.
      This requirement for hSNM1B in the cellular response to ICL has been hypothesized
      before but never experimentally verified. In addition, siRNA knockdown of hSNM1B
      rendered cells sensitive to ionizing radiation, suggesting the possibility of
      hSNM1B involvement in homologous recombination repair of double-strand breaks
      arising as intermediates of ICL repair. Monoubiquitination of FANCD2, a key step
      in the FANC/BRCA pathway, is not affected in hSNM1B-depleted HeLa cells,
      indicating that hSNM1B is probably not a part of the Fanconi anemia core complex.
      Nonetheless, similarities in the phenotype of hSNM1B-depleted cells and cultured
      cells from patients suffering from Fanconi anemia make hSNM1B a candidate for one
      of the as yet unidentified Fanconi anemia genes not involved in
      monoubiquitination of FANCD2.

PMID- 15467759
TI  - Downregulation of ICAM-1 and VCAM-1 expression in endothelial cells treated by
      photodynamic therapy.
AB  - Photodynamic therapy (PDT) is a treatment for cancer and several noncancerous
      proliferating cell diseases that depends on the uptake of a photosensitizing
      compound followed by selective irradiation with visible light. In the presence of
      oxygen, irradiation leads to the production of reactive oxygen species (ROS). A
      large production of ROS induces the death of cancer cells by apoptosis or
      necrosis. A small ROS production can activate various cellular pathways. Here, we
      show that PDT by pyropheophorbide-a methyl ester (PPME) induces the activation of
      nuclear factor kappa B (NF-kappaB) in HMEC-1 cells. NF-kappaB is active since it
      binds to the NF-kappaB sites of both ICAM-1 and vascular cell adhesion molecule-1
      (VCAM-1) promoters and induces the transcription of several NF-kappaB target
      genes such as those of IL-6, ICAM-1, VCAM-1. In contrast, expression of ICAM-1
      and VCAM-1 at the protein level was not observed, although we measured an IL-6
      secretion. Using specific chemical inhibitors, we showed that the lack of ICAM-1
      and VCAM-1 expression is the consequence of their degradation by lysosomal
      proteases. The proteasome and calpain pathways were not involved. All these
      observations were consistent with the fact that no adhesion of granulocytes was
      observed in these conditions.

PMID- 15467760
TI  - Estrogen-induced proliferation of normal endometrial glandular cells is initiated
      by transcriptional activation of cyclin D1 via binding of c-Jun to an AP-1
      sequence.
AB  - To explore the mechanism of estrogen-induced growth of normal endometrium, the
      transactivation system of the cyclin D1 gene was analysed using cultured normal
      endometrial glandular cells. Estradiol (E2) treatment of cultured normal
      endometrial glandular cells induced upregulation of c-Jun, and then cyclin D1
      proteins, followed by serial expressions of cyclins E, A and B1 proteins.
      Increase in the mRNA expression of cyclin D1 preceded the protein expression of
      cyclin D1 under E2 treatment. A luciferase assay using deletion constructs of the
      cyclin D1 promoter indicated that E2-induced increase in transcriptional activity
      was observed in reporters containing AP-1-binding site sequence, and that in the
      absence of E2, cotransfection of c-Jun also showed increase of transcriptional
      activity in the same reporters with AP-1 sequence. A gel shift assay using
      nuclear extract from E2-treated endometrial glandular cells and AP-1 sequences of
      the cyclin D1 promoter indicated specific binding between c-Jun protein and the
      promoter. Transfection of c-jun antisense oligonucleotides to the glandular cells
      resulted in the suppression of the E2-induced upregulation of cyclin D1 mRNA and
      protein. These findings suggest that E2-induced proliferation of normal
      endometrial glandular cells is initiated by transcriptional activation of cyclin
      D1 via binding of c-Jun to the AP-1 sequences.

PMID- 15467761
TI  - Inactivation of the RRB1-Pescadillo pathway involved in ribosome biogenesis
      induces chromosomal instability.
AB  - Since chromosomal instability (CIN) is a hallmark of most cancer cells, it is
      essential to identify genes whose alteration results into this genetic
      instability. Using a yeast CIN indicator strain, we show that inactivation of the
      YMR131c/RRB1 gene, which is involved in early ribosome assembly and whose
      expression is induced when the spindle checkpoint is activated, alters chromosome
      segregation and blocks mitosis at the metaphase/anaphase transition. We
      demonstrate that RRB1 interacts with YPH1 (yeast pescadillo homologue 1) and
      other members of the Yph1 complex, RPL3, ERB1 and ORC6, involved in ribosome
      biogenesis and DNA replication. Transient depletion of the human homologues GRWD,
      Pescadillo, Rpl3, Bop1 and Orc6L resulted in an increase of abnormal mitoses with
      appearance of binucleate or hyperploid cells, of cells with multipolar spindles
      and of aberrant metaphase plates. If deregulation of proteins involved in
      ribosome biogenesis, commonly observed in malignant tumors, could contribute to
      cancer through an aberrant protein synthesis, our study demonstrates that
      alteration of proteins linking ribosome biogenesis and DNA replication may
      directly cause CIN.

PMID- 15467762
TI  - The broad-range cyclin-dependent kinase inhibitor UCN-01 induces apoptosis in
      colon carcinoma cells through transcriptional suppression of the Bcl-x(L)
      protein.
AB  - The broad-range cyclin-dependent kinase inhibitor 7-hydroxystaurosporine (UCN-01)
      is known to induce both a G1 cell cycle arrest and apoptosis. The mechanism of
      UCN-01-induced apoptosis is largely unknown. We analysed the mechanism of
      cytotoxicity of UCN-01 in four established colon carcinoma cell lines. The cell
      lines SW48 and LS513 responded to UCN-01 treatment by undergoing apoptosis in a
      concentration-dependent manner while the cell lines HT-29 and WiDr were
      completely resistant. Apoptosis in LS513 and SW48 cell lines was concomitant with
      the suppression of Bcl-x(L) on mRNA and protein level. In contrast, in the
      apoptosis-resistant cell lines, Bcl-x(L) expression was not affected by UCN-01.
      Stable overexpression of the Bcl-x(L) protein abrogated UCN-01-triggered
      apoptosis, but only partially restored growth, indicating that both cell cycle
      arrest and apoptosis exert the anticancer effect in a coordinated manner. The
      inhibition of Akt phosphorylation did not correlate with the apoptotic phenotype.
      UCN-01 inhibited the activating STAT3 phosphorylations on Ser727 and, notably, on
      Tyr705, but STAT3 did not contribute to Bcl-x(L) expression in colon carcinoma
      cells. Moreover, we show for the first time that UCN-01 induces apoptosis by
      suppression of Bcl-x(L) expression. The inhibition of this pathway is a new
      aspect of cytotoxic and modulatory potential of UCN-01.

PMID- 15467763
TI  - Identification of 27 5' CpG islands aberrantly methylated and 13 genes silenced
      in human pancreatic cancers.
AB  - Aberrantly methylated DNA fragments were searched for in human pancreatic
      cancers, using the genome scanning technique: methylation-sensitive
      representational difference analysis (MS-RDA). MS-RDA isolated 111 DNA fragments
      derived from CpG islands (CGIs), and 35 of them were from CGIs in the 5' regions
      of known genes. Methylation-specific PCR (MSP) of the CGIs in seven pancreatic
      cancer cell lines and two pancreatic ductal epithelial cell lines showed that 27
      CGIs in the 5' regions were aberrantly methylated in at least one of the cancer
      cell lines. Quantitative reverse-transcription-PCR analysis showed that
      downstream genes of all the CGIs were either not expressed or only very weakly
      expressed in cancer cell lines with the aberrant methylation. In the pancreatic
      ductal epithelial cell lines, 18 genes were expressed at various levels, and nine
      genes were not expressed at all. Treatment of a cancer cell line with a
      demethylating agent, 5-aza-2'-deoxycytidine, restored the expression of 13 genes,
      RASGRF2, ADAM23, NEF3, NKX2-8, HAND1, EGR4, PRG2, FBN2, CDH2, TLL1, NPTX1, NTSR1
      and THBD, showing their silencing by methylation of their 5' CGIs. MSP of 24
      primary pancreatic cancers showed that all these genes, except for THBD, were
      methylated in at least one cancer. Some of those were suggested to be potentially
      involved in pancreatic cancer development and progression.

PMID- 15467764
TI  - Lack of efficacy of troglitazone at clinically achievable concentrations, with or
      without 9-cis retinoic acid or cytotoxic agents, for hepatocellular carcinoma
      cell lines.
AB  - Although the PPARgamma agonist troglitazone has been shown to induce growth
      inhibition of hepatocellular carcinoma (HCC) cells at high concentration, this
      study indicates troglitazone does not significantly inhibit the growth of HCC
      cells at clinically achievable concentrations (1-10 microM), and this lack of
      activity could not be improved by the addition of 9-cis-retinoic acid.
      Furthermore, no synergistic effect was found between troglitazone and cytotoxic
      anticancer agents.

PMID- 15467765
TI  - Multiple cycles of intermittent chemotherapy in metastatic androgen-independent
      prostate cancer.
AB  - Recently, completed phase III studies demonstrated a survival benefit for a fixed
      number of cycles of docetaxel-containing chemotherapy treatment of androgen
      independent prostate cancer (AIPC). Management of patients who respond well to
      initial chemotherapy for AIPC remains ill-defined. We previously reported that in
      a select group of such patients, retreatment with the same regimen was feasible
      and was associated with quality of life gains. Here, we report that multiple
      cycles of such intermittent chemotherapy are feasible. We prospectively tested
      intermittent chemotherapy in eight AIPC patients responding to calcitriol plus
      docetaxel who reached a serum prostate-specific antigen (PSA) <4 ng ml(-1) (22%
      of the 37 patients who were initially treated with this regimen). Chemotherapy
      was suspended until a rise in PSA > or =50% and 1 ng ml(-1). The median duration
      of the first treatment holiday was 20 weeks (13-74 weeks) and all patients
      retained sensitivity to retreatment. Four patients were eligible for a second
      chemotherapy holiday, and the median duration was 21 weeks (17-28 weeks). Two
      patients elected to take a third chemotherapy holiday, which lasted 10 and 28
      weeks. The median time to treatment failure was 26.5 months (95% CI 23.6-29.4
      months), and the median survival is 41 months (95% CI 33.7-48.3 months). Multiple
      cycles of intermittent chemotherapy interrupted by clinically meaningful
      treatment holidays are feasible in a subset of AIPC patients treated with this
      docetaxel-containing regimen. Intermittent chemotherapy for AIPC is feasible and
      deserves further study.

PMID- 15467766
TI  - Multicentre phase II study of bifractionated CPT-11 with bimonthly leucovorin and
      5-fluorouracil in patients with metastatic colorectal cancer pretreated with
      FOLFOX.
AB  - This multicentre phase II study was designed to evaluate the antitumour activity
      and toxicity of bifractionated camptothecin (CPT-11) and 5-fluorouracil/
      leucovorin (5-FU/LV) in the treatment of patients with metastatic colorectal
      cancer (MCC) who had been pretreated with 5-FU/LV-oxaliplatin (FOLFOX regimen).
      In all, 35 patients were enrolled in a two-stage trial. Treatment consisted of
      two daily doses of CPT-11, 90 mg m2 administered over 90 min, followed by LV, 200
      mg m2 administered over 2 h plus 5-FU 400 mg m2 as a bolus and 600 mg m2 as a 22
      h continuous infusion administered with disposable pumps as outpatient therapy.
      Toxicity was closely monitored. Response was evaluated by computed tomography
      scans every 8 weeks. All 35 patients were assessable for toxicity and response to
      treatment. Seven patients had a partial response, giving an overall response rate
      of 20%; 11 patients had stable disease (31.4%) and 17 progressed (48.5%). The
      median progression-free survival was 7.1 months and median survival was 14
      months. A total of 10 patients (30%) experienced grade 3-4 toxicity, including
      nausea (15%), diarrhoea (12%) and neutropenia (15%), while seven patients (21%)
      had grade 2 alopecia. The bifractionated bimonthly schedule of CPT-11 plus 5
      FU/LV showed substantial antitumour activity and was well tolerated in this group
      of patients with a poor prognosis, pretreated with the FOLFOX regimen.

PMID- 15467767
TI  - S100A2 is strongly expressed in airway basal cells, preneoplastic bronchial
      lesions and primary non-small cell lung carcinomas.
AB  - S100A2 gene products were shown to be frequently and dramatically over
      represented in non-small cell lung cancer (NSCLC) lesions over normal tissue by
      microarray analysis. We have now analysed an independent series of NSCLC tumours
      and multiple matched normal bronchial epithelial sites by RT-PCR and
      immunohistochemistry to investigate: whether this expression pattern can be
      confirmed and whether elevated expression is associated with tumour histology,
      clinical outcome or preneoplasia. In this second series, S100A2 was strongly
      expressed in 76% (35 out of 46) of tumours, more frequently in squamous cell than
      adenocarcinomas (P<0.002). This strong expression was not related to high-level
      gene amplification, but was associated in one of five informative cases with an
      allele-specific imbalance in transcript levels. Most tumours strongly expressed
      the DeltaNp63 transcript, the product of which is a putative regulator of S100A2
      transcription and while all but one of the tumours positive for DeltaNp63
      expressed S100A2, others negative for this regulator also expressed the gene.
      Contrary to the hypothesis that S100A2 is a tumour suppressor, no somatic
      mutations were identified in the coding sequence in 44 tumours. Furthermore, an
      examination of multiple tumour-free epithelial sites from 20 patients showed that
      strong expression was often associated with increasing levels of disorder in
      preinvasive bronchial lesions (P<0.0001).

PMID- 15467768
TI  - An immunohistochemical study of TIMP-3 expression in oesophageal squamous cell
      carcinoma.
AB  - Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activity of matrix
      metalloproteinase, which may play an important role in carcinoma invasion and
      metastasis. We have investigated the relationship between TIMP-3 reduction and
      clinicopathological factors in oesophageal squamous cell carcinoma (ESCC). We
      examined tissue specimens that had been removed from 90 patients with thoracic
      oesophageal cancer who had undergone surgery between 1983 and 2001.
      Immunohistochemical staining was performed by the standard streptavidin-biotin
      method. Immunostaining of TIMP-3 was seen in the cytoplasm of cancer cells and
      normal oesophageal epithelial cells, particularly in cells located in shallow
      areas of the tumour. TIMP-3 preserved (+), moderate (+/-), and reduced (-) cases
      accounted for 30, 27, and 33 of the 90 patients, respectively (33, 30, 37%).
      Significant correlations were observed between TIMP-3 expression and depth of
      tumour invasion (P=0.001), number of lymph node metastases (P=0.003),
      infiltrative growth pattern (P=0.003), and disease stage (P=0.005). The survival
      rates of patients with TIMP-3 (-) cancer were significantly lower than those of
      patients with TIMP-3 (+) and TIMP-3 (+/-) cancer (P=0.0003). The mean 5-year
      survival rates of patients with TIMP-3 (+), (+/-), and (-) were 50, 58, and 21%,
      respectively. In conclusion, decreased expression of TIMP-3 protein correlates
      with invasive activity and metastasis. This makes the prognosis for patients with
      cancer that has lost TIMP-3 significantly less favourable than that for patients
      with cancer that has maintained TIMP-3.

PMID- 15467769
TI  - Development of spontaneous tumours and intestinal lesions in Fhit gene knockout
      mice.
AB  - The fragile histidine triad (FHIT) gene is frequently inactivated in various
      types of tumours. However, the system-wide pathology caused by FHIT inactivation
      has not been examined in detail. Here we demonstrate that Fhit gene knockout mice
      develop tumours in the lymphoid tissue, liver, uterus, testis, forestomach and
      small intestine, together with structural abnormalities in the small intestinal
      mucosa. These results suggest that Fhit plays important roles in systemic tumour
      suppression and in the integrity of mucosal structure of the intestines.

PMID- 15467770
TI  - Dietary induction of NQO1 increases the antitumour activity of mitomycin C in
      human colon tumours in vivo.
AB  - The bioreductive antitumour agent, mitomycin C (MMC), requires activation by
      reductive enzymes like NAD(P)H:quinone oxidoreductase 1 (NQO1). We used a novel
      approach to increase MMC efficacy by selectively inducing NQO1 in tumour cells in
      vivo. CD-1 nude mice were implanted with HCT116 cells, and fed control diet or
      diet containing 0.3% of the NQO1 inducer, dimethyl fumarate (DMF). The mice were
      then treated with saline, 2.0, 3.5 or 2.0 mg kg(-1) MMC and dicoumarol, an NQO1
      inhibitor. The DMF diet increased NQO1 activity by 2.5-fold in the tumours, but
      had no effect in marrow cells. Mice given control diet/2.0 mg kg(-1) MMC had
      tumours with the same volume as control mice; however, mice given DMF diet/2.0 mg
      kg(-1) MMC had significantly smaller tumours. Tumour volumes in mice given
      DMF/2.0 mg kg(-1) MMC were similar to those in mice given control diet/3.5 mg kg(
      1) MMC. Tumour inhibition was partially reversed in mice given DMF/2.0 mg kg(-1)
      MMC and dicoumarol. DMF diet/2.0 mg kg(-1) MMC treatment did not increase
      myelosuppression and did not produce any organ toxicity. These results provide
      strong evidence that dietary inducers of NQO1 can increase the antitumour
      activity of bioreductive agents like MMC without increasing toxicity.

PMID- 15467771
TI  - Breast cancer: patient information needs reflected in English and German web
      sites.
AB  - Individual belief and knowledge about cancer were shown to influence coping and
      compliance of patients. Supposing that the Internet information both has impact
      on patients and reflects patients' information needs, breast cancer web sites in
      English and German language were evaluated to assess the information quality and
      were compared with each other to identify intercultural differences. Search
      engines returned 10 616 hits related to breast cancer. Of these, 4590 relevant
      hits were analysed. In all, 1888 web pages belonged to 132 English-language web
      sites and 2702 to 65 German-language web sites. Results showed that palliative
      therapy (4.5 vs 16.7%; P=0.004), alternative medicine (18.2 vs 46.2%; P<0.001),
      and disease-related information (prognosis, cancer aftercare, self-help groups,
      and epidemiology) were significantly more often found on German-language web
      sites. Therapy-related information (including the side effects of therapy and new
      studies) was significantly more often given by English-language web sites: for
      example, details about surgery, chemotherapy, radiotherapy, hormone therapy,
      immune therapy, and stem cell transplantation. In conclusion, our results have
      implications for patient education by physicians and may help to improve patient
      support by tailoring information, considering the weak points in information
      provision by web sites and intercultural differences in patient needs.

PMID- 15467772
TI  - Effect of process standards on survival of patients with head and neck cancer in
      the south and west of England.
AB  - The aim of the study was to compare standards for the process of care and 2-year
      survival between two cohorts of patients with head and neck cancer in the south
      and west of England. A total of 566 and 727 patients presented in 1996-97 and
      1999-2000, respectively. The median number of cases treated per surgeon was 4
      (1997, range 1-26) and 4 (2000, 1-23) and per radiotherapist was 10 (1-51) and 19
      (1-70). For all 'nontemporal' standards, the overall standard increased, without
      reaching minimum high targets, while most 'waiting times' increased. Overall 2
      year survival was 64.1% in 1997 and 65.1% in 2000. There was no difference in
      survival between networks (range 56-68, 1997, log-rank test 4.1, P=0.4; 62-69,
      2000, log-rank test 1.26, P=0.69). Patients assessed by a multidisciplinary
      clinic exhibited improved survival (1997: P=0.1; 2000: hazard ratio 0.7, P=0.02),
      as did those with a pretreatment chest X-ray (hazard ratio 0.7, P=0.03). Despite
      an increased incidence, standards for the process of care for patients with head
      and neck cancer improved between 1996 and 2000, while waiting times increased and
      2-year survival rates remained unaltered. Two out of five networks demonstrated
      centralisation of services between audits. Being seen in a multidisciplinary
      clinic correlated strongly with patient survival.

PMID- 15467773
TI  - Measurement of abdominal fat by CT compared to waist circumference and BMI in
      explaining the presence of coronary calcium.
AB  - OBJECTIVE: To evaluate the association between standard and computed tomography
      (CT)-based measures of obesity and subclinical atherosclerosis, defined as
      coronary artery calcium (CAC) by Electron Beam Computed Tomography (EBCT).
      DESIGN: Cross-sectional, observational study of anthropometric and CT obesity
      measures and presence of CAC. SUBJECTS: Participants were 383 men and 379 women,
      aged 20-58 y and asymptomatic for coronary artery disease (CAD). MEASUREMENTS:
      Intra-abdominal fat (IAF) and subcutaneous fat (SQF) were measured at the level
      of lumbar 2-3 and 4-5 spaces, using EBCT. Body mass index (BMI) was calculated
      from height and weight, and minimum waist circumference and maximum hip
      circumference were measured. CAC was measured by EBCT. RESULTS: In both men and
      women, BMI, waist circumference, IAF, and SQF were significantly related to CAC.
      However, BMI or waist circumference explained variation in the presence of CAC as
      well as IAF or SQF, univariately and after adjustment for additional
      cardiovascular risk factors. CONCLUSION: CT-based obesity exposure measures are
      not superior to BMI or waist circumference in association studies of subclinical
      CAD.

PMID- 15467774
TI  - Changes in intake of fruits and vegetables in relation to risk of obesity and
      weight gain among middle-aged women.
AB  - OBJECTIVE: To examine the changes in intake of fruits and vegetables in relation
      to risk of obesity and weight gain among middle-aged women. DESIGN: Prospective
      cohort study with 12 y of follow-up conducted in the Nurses' Health Study.
      SUBJECTS: A total of 74,063 female nurses aged 38-63 y, who were free of
      cardiovascular disease, cancer, and diabetes at baseline in 1984. MEASUREMENTS:
      Dietary information was collected using a validated food frequency questionnaire,
      and body weight and height were self-reported. RESULTS: During the 12-y follow
      up, participants tended to gain weight with aging, but those with the largest
      increase in fruit and vegetable intake had a 24% of lower risk of becoming obese
      (BMI> or =30 kg/m2) compared with those who had the largest decrease in intake
      after adjustment for age, physical activity, smoking, total energy intake, and
      other lifestyle variables (relative risk (RR), 0.76; 95% confidence interval
      (CI), 0.69-0.86; P for trend <0.0001). For major weight gain (> or =25 kg), women
      with the largest increase in intake of fruits and vegetables had a 28% lower risk
      compared to those in the other extreme group (RR, 0.72; 95% CI, 0.55-0.93;
      P=0.01). Similar results were observed for changes in intake of fruits and
      vegetables when analyzed separately. CONCLUSIONS: Our findings suggest that
      increasing intake of fruits and vegetables may reduce long-term risk of obesity
      and weight gain among middle-aged women.

PMID- 15467775
TI  - Lipid peroxides in obese patients and effects of weight loss with orlistat on
      lipid peroxides levels.
AB  - OBJECTIVE: Obesity is a well-known risk factor of atherosclerosis. Recent studies
      showed that obesity is associated with enhanced lipid peroxidation. The aim of
      this study is to investigate the effect of weight reduction with orlistat
      treatment on lipid peroxidation levels. We assessed lipid peroxidation by
      measuring the concentration of plasma malondialdehyde (MDA). DESIGN: A
      randomized, controlled, open-label 6-month study. SUBJECTS: In total, 36 obese
      (body mass index (BMI) >30 kg/m2) and 11 healthy age-matched control subjects
      were enrolled in the study. MEASUREMENTS: Fasting glucose, triglyceride, total
      cholesterol, HDL cholesterol and LDL cholesterol and MDA levels were measured in
      both groups. Obese subjects received orlistat, 120 mg three times daily together
      with hypocaloric diet. After 6 months of treatment laboratory tests were
      repeated. RESULTS: MDA levels were significantly higher in obese patients than
      the control group (P<0.0001). After 6 months of treatment in obese subjects, the
      mean weight of the patients decreased by 6.8 kg, the BMI by 3.2 kg/m2. Plasma MDA
      levels were significantly reduced by weight loss from 2+/-0.77 to 0.89+/-0.41
      nmol/ml (P<0.001). BMI correlated with MDA levels at baseline (r=0.6, P<0.0001).
      Changes in BMI was positively associated with plasma MDA level reduction (r=0.36,
      P<0.05). CONCLUSION: These results indicate that obesity is associated with
      increases in endogenous lipid peroxides. Our data show that the indicator of
      lipid peroxidation-MDA-falls markedly in association with weight loss with
      orlistat. The demonstration of decreased free radical generation has important
      implications for oxidative mechanism underlying obesity-associated disorders.

PMID- 15467776
TI  - Feasibility of a partial meal replacement plan for weight loss in low-income
      patients.
AB  - BACKGROUND: Low-income patients are disproportionately affected by obesity.
      Routine care is available to this population at the Venice Family Clinic (VFC) in
      Los Angeles. The current study examined the effectiveness of nutrition clinic
      utilizing meal replacements (Slim-Fast, Slim-Fast Foods Co., FL, USA) in low
      income patients over a 6-month period compared with the routine care by their
      primary care physician (PMD) prior to enrolling in the nutrition clinic at
      similar time intervals. METHODS: In total, 63 patients (51 F; 49+/-0.8 yo) who
      had been followed at the VFC by their PMD for at least 6 months were enrolled in
      this study. Patients had a body mass index (BMI) of 40+/-1.1 kg/m2, were 72%
      Hispanic, 25% Caucasian, and 3% African American. They had the following co
      morbidities: hypertension (HTN) 45%, diabetes mellitus II (DM II) 50%,
      gastroesophageal reflux disease (GERD) 34%, osteoarthritis 51%, and
      hypercholesterolemia 48%. All patients were provided with meal replacements to be
      taken twice a day and were instructed to consume one complete low calorie meal
      per day. Weights at the first visit to the nutrition clinic, 1, 3, and 6 months
      after enrollment in nutrition clinic were compared to their weights at the same
      time intervals during routine visits to their PMD prior to enrollment in the
      nutrition clinic. RESULTS: There was no significant weight change during the 6
      months prior to enrollment in the nutrition program despite receiving care by a
      PMD. At 6 months after participating in the nutrition program, there was a mean
      decrease of 7% body weight with a reduction in BMI from 40-37 kg/m2 (P< or
      =0.05). CONCLUSION: Implementation of nutrition clinic utilizing meal
      replacements in this low-income patient population was effective in achieving a
      significant reduction in weight over 6 months of treatment..

PMID- 15467777
TI  - Flow-resistant red blood cell aggregation in morbid obesity.
AB  - OBJECTIVE: Enhanced red blood cell (RBC) aggregation has an adverse effect on
      microcirculatory blood flow and tissue oxygenation. It has been previously shown
      that obesity is associated with increased RBC aggregation. The objectives of the
      present study were to further characterize obesity-related RBC aggregation and to
      examine whether the enhanced aggregation is a plasma- or cellular-dependent
      process. METHODS: Obese (body mass index (BMI)=40+/-6.3 kg/m2, n=22) and nonobese
      (BMI=24+/-3.4 kg/m2, n=18) individuals were evaluated for inflammation markers
      and aggregation parameters. Aggregation parameters were derived from the
      distribution of RBC population into aggregate sizes, and from the variation of
      the distribution as a function of flow-derived shear stress, using a cell flow
      properties analyzer. To differentiate plasmatic from cellular factors, we
      determined the aggregation in the presence of autologous plasma or dextran-500
      kDa and calculated the plasma factor (PF) in the obese group. PF ranges from 0 to
      1. When the PF=1, the aggregation is all due to plasmatic factors, when PF=0, the
      altered aggregation depends entirely on cellular factors, whereas 0<PF<1 reflects
      the joint contribution of cellular and plasmatic factors. RESULTS: Obese subjects
      had relatively larger aggregates that were more resistant to dispersion by flow.
      The calculated PF in the obese group was 0.9, indicating a pronounced
      contribution of plasma to RBC aggregation in obesity. DISCUSSION: Our results
      suggest that obese individuals present pathological plasma-dependent RBC
      aggregation, which is probably triggered by plasma macromolecules associated with
      the inflammatory response. These findings impact the future attempts to develop
      strategies aimed at attenuation of the enhanced RBC aggregation in obese
      individuals.

PMID- 15467778
TI  - Influence of social class on time trends in BMI distribution in 5-year-old French
      children from 1989 to 1999.
AB  - AIMS: To assess the prevalence of obesity and changes in body mass index (BMI)
      distribution between 1989 and 1999 in 5-y-old children, and to study the
      influence of parental socioeconomic status on these parameters. METHODS: Two
      cohorts of children in the final year of nursery school (in the city of Lille,
      France) were enrolled in 1989 (705 children: mean age=5.6+/-0.4 y) and 1999 (1258
      children: mean age=5.6+/-0.5 y). Weight and height were measured, and data about
      parental occupation were collected during a school medical examination.
      International Obesity Task Force cutoff points were used to define overweight and
      obesity. Parental occupation was classified into four categories. RESULTS: The
      prevalence of obesity increased from 1.8 to 4.9%, and the prevalence of
      overweight rose from 9.6 to 16.9%. Mean-difference plots allowed qualitative
      comparisons of the BMI distribution between the surveys: for children from the
      highest social classes, there was no change in BMI; for children from
      intermediate classes, there was a up-shift only in the upper part of the
      distribution with the heaviest children becoming heavier still; finally, for
      children from the lowest class, there was an increase in BMI across the entire
      population. CONCLUSIONS: This study of the changes in BMI distribution gives
      greater insight into the 'obesity epidemic'. Our results show the influence of an
      interaction between genetic and environmental factors. The increase in BMI in the
      upper part of the distribution suggests that this is a population with a high
      degree of susceptibility, whereas the increase in BMI across the whole population
      in the lowest social class suggests a strong influence of the environment on this
      group and thus the necessity of appropriate, preventive measures.

PMID- 15467779
TI  - Novel short-term effects of adenovirus Ad-36 on hamster lipoproteins.
AB  - OBJECTIVE: Human adenovirus Ad-36 induces adiposity and lowers total serum
      cholesterol in chickens, mice and marmosets and Ad-36 antibodies are associated
      with human obesity. We examined the early effects of Ad-36 inoculation on plasma
      cholesterol levels in hamsters fed a hyperlipidemic diet. DESIGN: A total of 32
      male Golden Syrian hamsters were divided into two equal weight-matched groups and
      intranasally inoculated with Ad-36 (INF: infected) or media (CON: control). In
      each group, the animals were fed either a purified diet (PF, n=8) 40%en fat +/
      194 mg cholesterol/1000 kcal or chow (C, n=8) ad libitum. Animals were killed 5
      weeks postinoculation. RESULTS: Nested PCR assay detected Ad-36 DNA in the lung,
      liver, visceral adipose tissue and skeletal muscle of the INF group, but not in
      the CON animals. Ad-36 antibodies were detected in the INF group only. For all
      animals, total plasma cholesterol (TC) was not significantly affected by Ad-36
      treatment (203+/-92 vs 193+/-75 mg/dl, P=NS; INF vs CON, respectively). In 5
      weeks, Ad-36 infection had no effect on TC concentration in hamsters fed chow
      (128+/-39 vs 130+/-27 mg/dl, INF-C vs CON-C, respectively) or those fed PF (269+/
      70 vs 256+/-47 mg/dl, INF-P vs CON-P, respectively). However, lipoproteins
      isolated by density gradient ultracentrifugation showed a greater proportion of
      LDL cholesterol in INF animals, as compared to CON (28.4+/-1.6% vs 16.4+/-1.2%,
      P=0.02), regardless of dietary treatment (INF-P vs CON-P: 27.3+/-2.1 vs 15.7+/
      1.5%, P=0.07; and INF-C vs CON-C: 29.4+/-1.2 vs 17.0+/-1.1%, P=0.009). This shift
      appears to be from HDL cholesterol to the LDL fractions. CONCLUSION: These data
      suggest that in the hamster (a model resembling several aspects of human
      lipoprotein metabolism), Ad-36 infection may acutely affect the intravascular
      processing of lipoproteins resulting in a more atherogenic lipoprotein profile.

PMID- 15467780
TI  - Pharmacogenetics research network and knowledge base fourth scientific meeting.

PMID- 15467781
TI  - Localization of sequences in wheat endosperm protein genes which confer tissue
      specific expression in tobacco.
AB  - The developing cereal grain accumulates large quantities of proteins which are
      unique to the endosperm tissue. The DNA sequences which determine their endosperm
      specific expression have not yet been identified. In the absence of a suitable
      transformation-regeneration system for cereals, we have investigated whether
      chimaeric genes consisting of low mol. wt (LMW) and high mol. wt (HMW) glutenin
      gene upstream sequences coupled to the coding region of the bacterial
      chloramphenicol acetyl transferase (CAT) gene could be specifically expressed in
      transgenic tobacco. The fusions, made in a Ti-derived binary vector, were
      introduced into tobacco via Agrobacterium tumefaciens-mediated transformation and
      their activity assayed. Both the LMW and HMW glutenin chimaeric genes exhibited
      endosperm-specific CAT activity in the transformed plants. In addition, a
      deletion series of the LMW glutenin sequence indicated that sequences present
      between 326 bp and 160 bp upstream of the transcription start point are necessary
      to confer endosperm-specific CAT activity.

PMID- 15467782
TI  - Azospirillum-plant relationships: physiological, molecular, agricultural, and
      environmental advances (1997-2003).
AB  - This review presents a critical and comprehensive documentation and analysis of
      the developments in agricultural, environmental, molecular, and physiological
      studies related to Azospirillum cells, and to Azospirillum interactions with
      plants, based solely on information published between 1997 and 2003. It was
      designed as an update of previous reviews (Bashan and Levanony 1990; Bashan and
      Holguin 1997a), with a similar scope of interest. Apart from an update and
      critical analysis of the current knowledge, this review focuses on the central
      issues of Azospirillum research today, such as, (i) physiological and molecular
      studies as a general model for rhizosphere bacteria; (ii) co-inoculation with
      other microorganisms; (iii) hormonal studies and re-consideration of the nitrogen
      contribution by the bacteria under specific environmental conditions; (iv)
      proposed Azospirillum as a non-specific plant-growth-promoting bacterium; (v) re
      introduction of the "Additive Hypothesis," which suggests involvement of multiple
      mechanisms employed by the bacteria to affect plant growth; (vi) comment on the
      less researched areas, such as inoculant and pesticide research; and (vii)
      proposes possible avenues for the exploitation of this bacterium in environmental
      areas other than agriculture.

PMID- 15467783
TI  - Preservation of in vitro cultures of the mite pathogenic fungus Neozygites
      tanajoae.
AB  - Neozygites tanajoae has recently been described as a new fungal pathogen distinct
      from Neozygites floridana. This pathogen is currently being used as a classical
      biological control agent against the cassava green mite, Mononychellus tanajoa
      (Bondar), in Africa. Neozygites tanajoae is a particularly fastidious species,
      and in vitro cultures of isolates from Brazil and Africa have only recently been
      established. In this study, the efficacy of several cryoprotectants at different
      exposure times, cooling rates, and warming rates for protecting hyphal bodies of
      N. tanajoae during cryopreservation was investigated. A protocol for preservation
      of cultures of N. tanajoae at ultra-low temperatures of -80 degrees C or -196
      degrees C, using 1% trehalose + 2% dimethyl sulfoxide as cryoprotective agents,
      is described in detail. In this study, we demonstrate that N. tanajoae differs
      remarkably from N. floridana (isolates ARSEF 662 and ARSEF 5376) in the ability
      to withstand the stress of cold temperature (4 degrees C) and cryopreservation.
      In vitro cultures of the 2 N. floridana isolates remained viable at 4 degrees C
      for up to 47 d; however, cultures of N. tanajoae did not survive this temperature
      for 4 d. Cryopreservation methods successful for N. tanajoae isolates are not
      suitable for N. floridana and are unusual in comparison to those for many fungi.

PMID- 15467784
TI  - Pig slurry reduces the survival of Ralstonia solanacearum biovar 2 in soil.
AB  - The effect of added pig slurry and solarization on the survival of Ralstonia
      solanacearum biovar 2 strain 1609 in soil was analysed in soil microcosms and
      field plots. In addition, the invasion of potato plants by R. solanacearum and
      the development of disease symptoms were determined, as measures of induced
      disease suppressiveness. In untreated soil, R. solanacearum showed slow
      population declines in both microcosms and the field from, initially, 10(6-)10(7)
      to 10(3)-10(4) CFU.(g dry soil)(-1) in about 9 weeks. The suppressiveness assays
      of these untreated soils after this period revealed that most of the plants that
      were used developed wilting symptoms and (or) contained the pathogen in their
      lower stem parts, as shown by immunofluorescence colony staining and PCR. The
      addition of pig slurry resulted in a significantly lower population size of R.
      solanacearum as well as reduced numbers of infected and (or) diseased plants in
      the soil suppressiveness tests. On the other hand, solarization of soil also
      decreased R. solanacearum survival but did not enhance soil suppressiveness as
      measured by development of disease symptoms and (or) plant invasion after 9
      weeks. Combined soil solarization and pig slurry addition showed an additive
      effect of both treatments. Healthy-looking plants, primarily from soils treated
      with pig slurry and solarization, incidentally revealed the latent presence of R.
      solanacearum in the lower stem parts. The mechanism behind the enhanced
      population declines and disease suppressiveness induced by pig slurry is unclear
      but shifts in community profiles were clearly discernible by PCR - denaturing
      gradient gel electrophoresis 9 weeks after pig slurry addition in the field
      experiment, indicating induced changes in the bacterial community structure.

PMID- 15467785
TI  - Field and soil microcosm studies on the survival and conjugation of a Pseudomonas
      putida strain bearing a recombinant plasmid, pADPTel.
AB  - Pseudomonas putida CR30RNS (pADPTel) is an antibiotic-resistant strain with a
      recombinant plasmid that confers resistance to tellurite and the ability to
      catabolize atrazine. The survival of this strain as well as its ability to
      transfer genes for atrazine degradation and tellurite resistance to indigenous
      soil bacteria were tested in both fallow soil and canola (Brassica napus)
      rhizosphere by the use of parallel field and laboratory releases. Culturable
      CR30RNS (pADPTel) were enumerated in field and microcosm soils at 7- to 14-day
      intervals over 49 d. Strain CR30RNS (pADPTel) survived for up to 7 weeks in
      microcosm soils at a density of 10(4) CFU/g soil, whereas in field soils the
      population declined to 10(3) CFU/g soil by the fourth week. In contrast, when
      CR30RNS (pADPTel) was introduced into the soil as a seed coating of canola (B.
      napus 'Karoo'), the bacterium established at higher cell densities in the
      rhizosphere (10(6)-10(5) CFU/g fresh root mass), with no subsequent decrease in
      numbers. The presence of selective pressure (i.e., atrazine) had no significant
      effect on the survival of CR30RNS (pADPTel) in either field or microcosm soils.
      One year postinoculation field sites were examined for the presence of CR30RNS
      (pADPTel) and no evidence of culturable parental cells was observed when samples
      were plated onto selective media. However, the atzC and telAB gene segments were
      amplified from the field soils at that time. Under laboratory conditions,
      indigenous soil bacteria were capable of receiving and expressing the engineered
      plasmid construct at frequencies ranging from 1 to 10(-3) transconjugants per
      donor. However, no plasmid transfer to indigenous soil bacteria was detected in
      the field or microcosm soils regardless of the presence of canola rhizosphere and
      (or) the application of atrazine. Our results show that the survival and
      population size of P. putida CR30RNS (pADPTel) might be sufficient for
      degradation of environmental pollutants but that the transfer frequency was too
      low to be detected under the conditions of this study.

PMID- 15467786
TI  - Diversity of cry genes and genetic characterization of Bacillus thuringiensis
      isolated from Brazil.
AB  - Two hundred and eighteen Bacillus thuringiensis isolates from Brazil were
      characterized by the presence of crystal protein genes by PCR with primers
      specific to different cry and cyt genes. Among these isolates, 95 were selected
      according to their geographic origin for genetic characterization with the 16S
      rRNA gene, RAPD, and plasmid profile. Isolates containing cry1 genes were the
      most abundant (48%) followed by the cry11 and cyt (7%) and cry8 genes (2%).
      Finally, 40.3% of the isolates did not produce any PCR product. The plasmid
      profile and RAPD analysis showed a remarkable diversity among the isolates of B.
      thuringiensis not observed in the 16S rRNA gene. These results suggest that the
      genetic diversity of B. thuringiensis species results from the influence of
      different ecological factors and spatial separation between strains generated by
      the conquest of different habitats.

PMID- 15467787
TI  - Molecular and physiological comparisons between Saccharomyces cerevisiae and
      Saccharomyces boulardii.
AB  - In this paper, comparative molecular studies between authentic Saccharomyces
      cerevisiae strains, related species, and the strain described as Saccharomyces
      boulardii were performed. The response of a S. boulardii strain and a S.
      cerevisiae strain (W303) to different stress conditions was also evaluated. The
      results obtained in this study show that S. boulardii is genetically very close
      or nearly identical to S. cerevisiae. Metabolically and physiologically, however,
      it shows a very different behavior, particularly in relation to growth yield and
      resistance to temperature and acidic stresses, which are important
      characteristics for a microorganism to be used as a probiotic.

PMID- 15467788
TI  - Determining the environmental fate of a filamentous fungus, Trichoderma reesei,
      in laboratory-contained intact soil-core microcosms using competitive PCR and
      viability plating.
AB  - Trichoderma spp. are used extensively in industry and are routinely disposed of
      in landfill sites as spent biomass from fermentation plants. However, little is
      known regarding the environmental fate of this biomass. We tracked the survival
      of T. reesei strain QM6A#4 (a derivative of strain QM6A marked with a recombinant
      construct) over a 6-month period in laboratory-contained, intact soil-core
      microcosms incubated in a growth chamber. Survival was tested in 3 different
      soils and the effect of a plant rhizosphere (bush lima beans, Phaseolus limensis)
      was investigated. Levels and viability of the fungus were determined,
      respectively, by quantitative competitive polymerase chain reaction analysis of
      total soil DNA extracts and dilution-plating of soil on a semiselective growth
      medium. Whereas chemically killed QM6A#4 became undetectable within 3 d, QM6A#4
      added as a live inoculum decreased approximately 4- to approximately 160-fold
      over the first 1-3 months and then reached a steady state. After 4 months, soil
      cores were subjected to a 1.5-month simulated winter period, which did not
      significantly affect QM6A#4 levels. Throughout the experiment, QM6A#4 remained
      viable. These results indicate that, following release into the environment, live
      T. reesei will persist in soil for at least 2 seasons.

PMID- 15467789
TI  - A survey of the composition and diversity of bacterial populations in bleached
      kraft pulp-mill wastewater secondary treatment systems.
AB  - Bacterial community compositions from 10 pulp- and paper-mill treatment systems
      were compared using both traditional and molecular techniques. 16S-RFLP (Random
      Fragment Length Polymorphisms) analysis was used to examine the genotypic
      profiles of the whole bacterial community of each treatment system. Although all
      the communities shared approximately 60% of their DNA band pattern, as determined
      by computer-assisted cluster analysis, each community displayed a unique profile
      that was stable over time under normal operating parameters. Reverse Sample
      Genome Probing (RSGP) and 16S-RFLP were used to compare the culturable bacterial
      communities of several geographically separated pulp-mill biotreatment system
      communities. There was little overlap in the composition of the culturable
      community between mills at the genus level. Furthermore, RSGP variation was
      almost as high within a mill as between mills. Partial sequences of the 16S rRNA
      genes from culturable isolates identified Bacillus spp., Pseudomonas spp., and
      Xanthobacter as some of the dominant species. Finally, several 16S rRNA genes
      from two whole community 16S RNA gene libraries were partially sequenced and
      identified as similar to unknown alpha-, beta-, and gamma-Proteobacteria,
      Ralstonia, Alcaligenes, Nitrospira, Firmicutes, and clones representing the new
      Holophaga/Acidobacterium phylum. These findings suggest that although these pulp-
      and paper-mill biotreatment communities perform similar functions, they are
      populated by unique mixtures of species.

PMID- 15467790
TI  - Isolation and transcriptional regulation of the Kluyveromyces lactis FBA1
      (fructose-1,6-bisphosphate aldolase) gene.
AB  - Cloning and transcriptional regulation of the KlFBA1 gene that codes for the
      class II fructose-1,6-bisphosphate aldolase of the yeast Kluyveromyces lactis are
      described. KlFBA1 mRNA diminishes transiently during the shift from hypoxic to
      fully aerobic conditions and increases in the reversal shift. This regulation is
      mediated by heme since expression was higher in a mutant defective in heme
      biosynthesis. KlFBA1 transcription is not induced by calcium-shortage, low
      temperature, or at stationary phase. These data suggest that KlFBA1 plays a role
      in the balance between oxidative and fermentative metabolism and that this gene
      is differentially regulated in K. lactis and Saccharomyces cerevisiae, i.e., a
      respiratory vs. fermentative yeast.

PMID- 15467791
TI  - Increased frequency of drug-resistant bacteria and fecal coliforms in an Indiana
      Creek adjacent to farmland amended with treated sludge.
AB  - Many studies indicate the presence of human pathogens and drug-resistant bacteria
      in treated sewage sludge. Since one of the main methods of treated sewage
      disposal is by application to agricultural land, the presence of these organisms
      is of concern to human health. The goal of this study was to determine whether
      the frequency of drug-resistant and indicator bacteria in Sugar Creek, which is
      used for recreational purposes, was influenced by proximity to a farmland
      routinely amended with treated sludge (site E). Surface water from 3 sites along
      Sugar Creek (site E, 1 upstream site (site C) and 1 downstream site (site K))
      were tested for the presence of ampicillin-resistant (Amp(R)) bacteria, fecal and
      total coliforms over a period of 40 d. Site E consistently had higher frequencies
      of Amp(R) bacteria and fecal coliforms compared with the other 2 sites. All of
      the tested Amp(R) isolates were resistant to at least 1 other antibiotic.
      However, no isolate was resistant to more than 4 classes of antimicrobials. These
      results suggest that surface runoff from the farmland is strongly correlated with
      higher incidence of Amp(R) and fecal coliforms at site E.

PMID- 15467792
TI  - [Clinical trial registration: a statement from the International Committee of
      Medical Journal Editors].

PMID- 15467793
TI  - [Fixing the price of psychiatry].

PMID- 15467794
TI  - [Addictive drugs are not for weaklings].

PMID- 15467795
TI  - [Withdrawal of addictive drugs--patients' experiences?].
AB  - BACKGROUND: The prescription of addictive drugs has been a cause for concern.
      Various small-scale interventions towards patients and doctors have proven
      effective in terms of cutting down the number of prescriptions. However, little
      is known about users' experience with withdrawal of addictive drugs; exploring
      this is the main aim of the present study. MATERIAL AND METHOD: Six focus group
      sessions with 27 former high and low dosage drug users, mainly of
      benzodiazepines, were conducted. All groups were audiotaped and analysed by
      qualitative methods. RESULTS AND INTERPRETATION: Five distinct themes emerged:
      reasons for drug use initiation, experience of being a user, experience related
      to drug withdrawal, of leading a life without medication, and experience with and
      expectations from doctors. Our group members pointed out that drug use was often
      initiated by the doctor and offered instead of counselling in acute crises.
      Information on side effects such as addictiveness was reported as largely absent.
      Both high and low dosage users reported a significant increase in self esteem and
      ability to cope that was directly related to drug withdrawal and they reported a
      substantially improved quality of life. Doctors seldom initiated drug reduction
      strategies and were largely regarded as absent during the withdrawal process. Our
      informants wanted better care, information and ability to communicate from their
      doctors, but also stricter prescription strategies and systematic control
      mechanisms.

PMID- 15467796
TI  - [Alu elements in the human genome].
AB  - BACKGROUND: The sequencing of the human genome has revealed that almost half of
      the genome consists of interspersed repeats. Among the different types of
      interspersed repeats in humans, Alu elements are the most frequent ones, and new
      Alu elements are still integrated into new positions in the humane genome. In
      this review some consequences of this Alu activity are discussed. The first part
      of the review is focused on Alu element activity that causes genetic disease
      while the use of Alu elements as genetic tools for several purposes is discussed
      in the last part. MATERIALS AND METHODS: This review article is based on a
      literature search on Medline. RESULTS AND INTERPRETATION: Alu elements cause
      disease by two different mechanisms. A de novo insertion of an Alu element into,
      or close to, a gene may disrupt its normal function, while homologous
      recombination between two Alu elements may result in deletions or duplications
      that cause genetic disease. The high density of Alu elements in the human genome
      combined with their absence in non-primate species make them useful as genetic
      tools. Alu elements also represent "molecular fossils" that give phylogenetic
      information about primates as well as information about historical DNA
      rearrangements in the human genome.

PMID- 15467798
TI  - [Parvovirus B19 infection--dangerous for the fetus].
AB  - BACKGROUND: Human parvovirus B19 infection is a common and usually benign disease
      in children, but may cause severe complications in pregnancy. We determined the
      proportion of the pregnant population at risk of infection and present a recent
      cluster of cases with fetal complications, hoping to raise the general awareness.
      MATERIAL AND METHODS: Five cases of fetal parvovirus B19 infection during 2001--2
      illustrate the delay in diagnosis, treatment and outcome. During the same period,
      the number of positive and negative serological tests was noted for the catchment
      area and the entire country. Additionally, 206 consecutive pregnant women were
      tested to determine susceptibility. RESULTS: Out of the five cases of fetal
      complications, all had cardiac involvement, three had anaemia, and two fetuses
      died. Lag-time to fetal diagnosis was six, eight, and 13 weeks for those with
      known maternal disease. In Norway, seroconversion is similar to that found in
      other Nordic countries; 36 % (74/206) of the pregnant population is seronegative.
      In Norway, parvovirus B19 infection is more frequently reported in the January
      June period. A third of the pregnant population is susceptible to infection.
      Early testing in cases of exposure or suspected infection in pregnancy is
      recommended in order to ensure appropriate follow-up and treatment.

PMID- 15467797
TI  - [Migraine and psychiatric disorders].
AB  - BACKGROUND: Migraine, mood disorders and anxiety disorders are common afflictions
      in the general population, with similar life-time prevalence rates, 10-20%. These
      disorders share many clinical features and the pathogenetic mechanisms may
      possibly be similar. MATERIAL AND METHODS: This review is based on Medline
      searches for relevant literature. RESULTS: Migraine typically occurs in the form
      of attacks. Panic disorder, the anxiety disorder most strongly linked to
      migraine, also occurs in attacks. Mood swings, both depressive and hypomanic, are
      often of short duration in many patients and can last only a couple of days;
      hence the course of these disorders has more similarities than is usually
      appreciated. Psychiatric symptoms are often seen in the course of a migraine
      attack. Epidemiological studies have shown strong comorbidity between these
      disorders. Migraine patients have higher prevalence of both anxiety disorders and
      depressions. There seems to be a particularly strong association between bipolar
      II disorder and migraine. Disturbances in monoaminergic systems, primarily the
      serotonergic, may represent pathophysiological mechanisms with regard to migraine
      and mood and anxiety disorders. Some drugs are effective in the treatment of all
      these disorders; the most important drugs are tricyclic antidepressants and
      valproate. INTERPRETATION: There are clear connections between migraine and
      psychiatric disorders and the attending physician should have them in mind.

PMID- 15467799
TI  - [Intravenous immunoglobulin in postpolio syndrome].
AB  - BACKGROUND: Postpolio syndrome is characterised by new muscular weakness, pain,
      and fatigue several decades after the acute polio, and affects approximately 1/4
      of patients with previous paralytic polio. MATERIAL AND METHODS: A 47-year-old
      woman with a previous history of acute poliomyelitis developed progressive
      muscular weakness in her left arm and right leg with muscular pain and fatigue.
      Clinical examination, MRI, and electromyography gave no other explanation to her
      progressive muscular weakness and fatigue than postpolio syndrome. She was
      treated with 400 mg/kg immunoglobulin intravenously for five consecutive days.
      RESULTS: At follow-up two and three months later, she had a considerable increase
      in isokinetic muscle strength in knee extension and flexion on the right side,
      and experienced less fatigue. INTERPRETATION: This case suggests that
      stabilisation of an autoimmune dysfunction may be a therapeutic option in
      postpolio syndrome.

PMID- 15467801
TI  - [Use of psychopharmaceuticals--should serum concentration be checked?].

PMID- 15467800
TI  - [Fine needle cytology of the thyroid gland].
AB  - BACKGROUND: Application of fine needle cytology (FNC) is important in the
      preoperative assessment of thyroid lesions. The method is rapid, minimally
      invasive and cost effective. The aim of this study was to evaluate the role of
      fine needle cytology at The Norwegian Radium Hospital in the management of
      thyroid nodules. MATERIAL AND METHODS: Data on FNC and comparable histology
      results were retrieved from the pathology database during the 5-year-period 1998
      through 2003. 1770 FNC samples and corresponding histology results from 443
      lesions were compared. Reviews of cytological slides were done in 39 discrepant
      cases and quality assessment parameters calculated. RESULTS: High complete
      sensitivity (77.5%) and specificity (90.1%) were found. The false positive rate
      was 1.2% and the false negative rate 23.7%. Inadequate FNCs were particularly
      seen in submitted specimens. A review of the discrepant cases showed that the
      main cause of false negative samples was sampling error. Micropapillary carcinoma
      was the predominant tumour type with false negative FNC. Eleven malignancies were
      diagnosed in repeat FNC specimens. INTERPRETATION: FNC is a highly reliable test
      to assess whether a thyroid nodule is benign or malignant. Diagnostic pitfalls
      are mainly due to inability to procure the diagnostic material.

PMID- 15467802
TI  - [The communicating body--eating disorders and culture].
AB  - What is "culture" in eating disorders as culture-bound syndromes? The human body
      is a flesh-and-blood entity, but it also functions as a symbolic instrument. The
      body communicates about culture itself, about norms and boundaries. In this paper
      one central aspect in the phenomenology of eating disorders is emphasised: The
      subjective experience of lack of control and the sense of an overwhelming
      "chaos", both on the inner and outer level. On this basis rapid societal
      transitions are discussed as specific pathogenic factors. Sociocultural
      instability represents insecure conditions for construction of a healthy and
      stable identity. "The open body" is a relevant metaphor, with its dialectical
      relationship to the isolation and delimitation represented by eating disordered
      behaviour. With reference to history and geography the paper also discusses the
      pathoplasticity of eating disorders; how they change in time and space. Cultural
      analysis of eating disorders can contribute to a richer understanding of the
      complexity of the construction of meaning in these disorders, both across
      cultures and within our own cultural contexts.

PMID- 15467803
TI  - [Eating disorders in a historical perspective].
AB  - Disordered eating has been known since antiquity and is mentioned in medical
      journals as well as in popular literature. The holy anorectics in the Middle Ages
      wanted to achieve spiritual perfection, while the anorectics of today are seeking
      bodily perfection. Hilde Bruch and Mara Selvini Palazzoli were the first to focus
      on anorectic symptoms like leanness and body image disturbance. The breakthrough
      in clinical and scientific work on bulimia nervosa came around 1980, primarily
      due to Russell's achievements. In 1874, Sir William Gull was the first to use
      anorexia nervosa as a diagnosis, while bulimia nervosa was first used in 1979. In
      the history of Norwegian psychiatry, several psychiatric disorders were described
      at an early stage, yet eating disorders have only been discussed in the
      scientific literature from the 1980s and onwards. Eating disorders have now
      become a cause of concern on the part of health authorities; their policy is to
      improve clinical skills at all levels rather than to build up specialised
      clinics.

PMID- 15467804
TI  - [Eating disorders in primary care].
AB  - Early diagnosis and treatment are important for the prognosis in eating disorders
      and will also reduce the burden on the patient as well as n his or her family. On
      the other hand, community studies show that less than half of clinical cases of
      eating disorders are identified in primary care; hence, better skills among
      general practitioners in this field are very important. On the basis of the
      literature and clinical experience, this article discusses various problems
      related to identifying, evaluating and treating patients with eating disorders in
      primary care. The most important tool for the general practitioner is an
      understanding of the nature of the disorder, but tools for identification and
      treatment are also useful. Attending the patient and collaboration with hospitals
      and outpatient clinics could be a challenge. There are guidelines for the
      treatment of eating disorders in specialised health care, including indications
      for hospitalisation, but no guidelines for referral to outpatient treatment or
      for the coordination between the general practitioner and specialised units. The
      proposed British guidelines might serve as a basis for Norwegian guidelines.

PMID- 15467805
TI  - [Cholecystectomy in Norway 1990-2002].
AB  - BACKGROUND: The purpose of this study was to investigate cholecystectomy
      incidence and laparoscopy rates in Norway (1990-2002). METHODS: Data were
      compiled from the Norwegian Patient Registry based on codes for cholecystectomy.
      RESULTS: From 1990 to 2000-02, age-adjusted incidence rate (per 10,000
      inhabitants) for cholecystectomy increased from 2.9 to 4.1 for men and from 7.0
      to 11.8 for women. Incidence rates varied between counties. The proportion
      undergoing laparoscopic surgery increased from 1% in 1990 to 89% in 2000-02. Over
      the same period the length of postoperative inpatient stay decreased from 7.3
      days to 3.3 days. 94% of electively admitted patients were operated by
      laparoscopic technique in 2000-02. Among patients admitted on an emergency basis,
      women below 50 were more often operated by laparoscopic technique than older
      women and men. CONCLUSION: Substantial changes in the treatment of gallstone
      disease occurred in Norway over the period 1990 -2002. Increased incidence rates
      for cholecystectomy and reduced length of postoperative inpatient stay were
      observed after the introduction of cholecystectomy by laparoscopic technique.

PMID- 15467806
TI  - [Activity-based financing in psychiatry, too?].

PMID- 15467807
TI  - [Chronic/post-viral fatigue syndrome].

PMID- 15467811
TI  - [Choosing correct total hip prosthesis].

PMID- 15467812
TI  - [Hip prostheses and cements].

PMID- 15467813
TI  - ["Reparative therapy" is unprofessional and unethical].

PMID- 15467814
TI  - [Simplified and not exact about antibiotics].

PMID- 15467815
TI  - [Use of antibiotics in sepsis].

PMID- 15467817
TI  - [Statins in hypertension].

PMID- 15467819
TI  - Taking the sting out of the anthrax vaccine.

PMID- 15467820
TI  - The economy of science.
AB  - We are in the midst of an era of plummeting pay lines at the NIH. History shows
      that when the federal deficit is high, NIH pay lines tend to fall, and the impact
      on biomedical research can be disastrous. Equally bad is the disincentive for the
      future generations of biomedical researchers who observe their mentors struggling
      to get adequate funding. How many bright young people will be turned away from
      careers in biomedical research? How much innovative science will be delayed or
      never initiated, how many new cures never realized? At a time of unprecedented
      challenges and remarkable technological advances that enable us to address those
      challenges, lack of funding is a threat to our society.

PMID- 15467821
TI  - From progress to regression: biomedical research funding.
AB  - Despite great advances in health-related research and health care, major
      challenges remain regarding the causes and cures of many diseases; these may be
      overcome with further research. Our society is enthusiastic about fostering such
      investigations. However, available federal funds limit many such projects.
      Previously there have been sizable increases in the NIH budget, but because of
      the escalating cost of scientific investigation and the pressures of financing
      other much-needed governmental programs, recent growth in biomedical research
      funding has barely kept up with inflation. This article focuses on select
      attempts to sustain the record of scientific achievement enabled in the past by
      continued increasing investment and also suggests some solutions.

PMID- 15467822
TI  - Challenges facing islet transplantation for the treatment of type 1 diabetes
      mellitus.
AB  - Islet transplantation represents a most impressive recent advance in the search
      for a type 1 diabetes mellitus cure. While several hundred patients have achieved
      at least temporary insulin independence after receiving the islet "mini-organs"
      (containing insulin-producing beta cells), very few patients remain insulin
      independent beyond 4 years after transplantation. In this review, we describe
      historic as well as technical details about the procedure and provide insight
      into clinical and basic research efforts to overcome existing hurdles for this
      promising therapy.

PMID- 15467823
TI  - Vasohibin: the feedback on a new inhibitor of angiogenesis.
AB  - Angiogenesis is regulated in large part by the balance of various proangiogenic
      stimulators, such as VEGF, and a diverse group of endogenous inhibitors of
      angiogenesis, most of which are extrinsic to endothelial cells. With respect to
      the latter, until recently, none have appeared to be induced as a consequence of
      a specific, self-regulating, feedback inhibition response. A new inhibitor,
      called vasohibin, has been uncovered. Vasohibin is selectively induced in
      endothelial cells by proangiogenic stimulatory growth factors such as VEGF; it
      appears to operate as an intrinsic and highly specific feedback inhibitor of
      activated endothelial cells engaged in the process of angiogenesis.

PMID- 15467824
TI  - IRS2 takes center stage in the development of type 2 diabetes.
AB  - The etiology of type 2 diabetes is characterized by obesity, insulin and leptin
      resistance, and compensatory beta cell hyperplasia followed by islet
      degeneration, resulting in the eventual dysregulation of glucose and lipid
      homeostasis. The recent identification of insulin receptor substrate 2 (IRS2) as
      a central player in the pathophysiology of many of these processes suggests a
      potentially unifying molecular link underlying the initiation and progression of
      type 2 diabetes.

PMID- 15467825
TI  - Lenti in red: progress in gene therapy for human hemoglobinopathies.
AB  - Hemoglobinopathies are caused by abnormal structure or synthesis of hemoglobin
      chains and represent serious monogenic disorders. A new study demonstrates that
      lentiviral vectors can express clinically relevant levels of human transgenic
      beta-globin in red cells of xenografted mice. While some safety concerns must be
      addressed, this study is an important step toward potential clinical trials of
      gene therapy for hemoglobinopathies.

PMID- 15467826
TI  - Gene therapy for type 1 diabetes: a novel approach for targeted treatment of
      autoimmunity.
AB  - It has been difficult to develop therapies that target those T cells initiating
      and mediating the pathogenesis of autoimmune disease. Indeed, most current
      treatments indiscriminately affect both the autoreactive T cells and the "good" T
      cells, putting the patient at risk of compromised immune function. A new approach
      raises the possibility of targeted therapy for autoimmunity. Transplantation of
      hematopoietic stem cells modified to express a protective form of MHC class II
      corrects a defect in central tolerance. This method contrasts with other targeted
      therapies that attempt to modify peripheral tolerance, which is also defective in
      type 1 diabetes mellitus.

PMID- 15467827
TI  - Judging a virus by its cover.
AB  - The production of protective neutralizing antibodies occurs quickly in some viral
      infections but very slowly in others. In a new study, surface glycoproteins (the
      targets of neutralization) of 2 different viruses were genetically switched.
      Analysis of the neutralizing antibody response to each of the 2 parent and
      recombinant viruses in infected mice revealed that the speed of neutralizing
      antibody induction was intrinsically dependent on the surface glycoprotein and
      not the rest of the virus.

PMID- 15467828
TI  - Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis.
AB  - Negative feedback is a crucial physiological regulatory mechanism, but no such
      regulator of angiogenesis has been established. Here we report a novel
      angiogenesis inhibitor that is induced in endothelial cells (ECs) by angiogenic
      factors and inhibits angiogenesis in an autocrine manner. We have performed cDNA
      microarray analysis to survey VEGF-inducible genes in human ECs. We characterized
      one such gene, KIAA1036, whose function had been uncharacterized. The recombinant
      protein inhibited migration, proliferation, and network formation by ECs as well
      as angiogenesis in vivo. This inhibitory effect was selective to ECs, as the
      protein did not affect the migration of smooth muscle cells or fibroblasts.
      Specific elimination of the expression of KIAA1036 in ECs restored their
      responsiveness to a higher concentration of VEGF. The expression of KIAA1036 was
      selective to ECs, and hypoxia or TNF-alpha abrogated its inducible expression. As
      this molecule is preferentially expressed in ECs, we designated it "vasohibin."
      Transfection of Lewis lung carcinoma cells with the vasohibin gene did not affect
      the proliferation of cancer cells in vitro, but did inhibit tumor growth and
      tumor angiogenesis in vivo. We propose vasohibin to be an endothelium-derived
      negative feedback regulator of angiogenesis.

PMID- 15467829
TI  - Dysregulation of insulin receptor substrate 2 in beta cells and brain causes
      obesity and diabetes.
AB  - The molecular link between obesity and beta cell failure that causes diabetes is
      difficult to establish. Here we show that a conditional knockout of insulin
      receptor substrate 2 (Irs2) in mouse pancreas beta cells and parts of the brain-
      including the hypothalamus--increased appetite, lean and fat body mass, linear
      growth, and insulin resistance that progressed to diabetes. Diabetes resolved
      when the mice were between 6 and 10 months of age: functional beta cells
      expressing Irs2 repopulated the pancreas, restoring sufficient beta cell function
      to compensate for insulin resistance in the obese mice. Thus, Irs2 signaling
      promotes regeneration of adult beta cells and central control of nutrient
      homeostasis, which can prevent obesity and diabetes in mice.

PMID- 15467830
TI  - Insulin receptor substrate 2 plays a crucial role in beta cells and the
      hypothalamus.
AB  - We previously demonstrated that insulin receptor substrate 2 (Irs2) KO mice
      develop diabetes associated with hepatic insulin resistance, lack of compensatory
      beta cell hyperplasia, and leptin resistance. To more precisely determine the
      roles of Irs2 in beta cells and the hypothalamus, we generated beta cell-specific
      Irs2 KO and hypothalamus-specific Irs2 knockdown (betaHT-IRS2) mice. Expression
      of Irs2 mRNA was reduced by approximately 90% in pancreatic islets and was
      markedly reduced in the arcuate nucleus of the hypothalamus. By contrast, Irs2
      expression in liver, muscle, and adipose tissue of betaHT-IRS2 mice was
      indistinguishable from that of control mice. The betaHT-IRS2 mice displayed
      obesity and leptin resistance. At 4 weeks of age, the betaHT-IRS2 mice showed
      normal insulin sensitivity, but at 8 and 12 weeks, they were insulin resistant
      with progressive obesity. Despite their normal insulin sensitivity at 8 weeks
      with caloric restriction, the betaHT-IRS2 mice exhibited glucose intolerance and
      impaired glucose-induced insulin secretion. beta Cell mass and beta cell
      proliferation in the betaHT-IRS2 mice were reduced significantly at 8 and 12
      weeks but not at 10 days. Insulin secretion, normalized by cell number per islet,
      was significantly increased at high glucose concentrations in the betaHT-IRS2
      mice. We conclude that, in beta cells and the hypothalamus, Irs2 is crucially
      involved in the regulation of beta cell mass and leptin sensitivity.

PMID- 15467831
TI  - Defective insulin secretion and increased susceptibility to experimental diabetes
      are induced by reduced Akt activity in pancreatic islet beta cells.
AB  - The insulin and IGF signaling pathways are critical for development and
      maintenance of pancreatic beta cell mass and function. The serine-threonine
      kinase Akt is one of several mediators regulated by these pathways. We have
      studied the role of Akt in pancreatic beta cell physiology by generating
      transgenic mice expressing a kinase-dead mutant of this enzyme in beta cells.
      Reduction of Akt activity in transgenic animals resulted in impaired glucose
      tolerance due to defective insulin secretion. The mechanisms involved in
      dysregulation of secretion in these mice lie at the level of insulin exocytosis
      and are not the result of abnormalities in glucose signaling or function of
      voltage-gated Ca2+ channels. Therefore, transgenic mice showed increased
      susceptibility to developing glucose intolerance and diabetes following fat
      feeding. These observations suggest that Akt plays a novel and important role in
      the regulation of distal components of the secretory pathway and that this enzyme
      represents a therapeutic target for improvement of beta cell function in
      diabetes.

PMID- 15467832
TI  - Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and
      apoptosis.
AB  - The Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathway
      regulates diverse cellular processes such as proliferation, differentiation, and
      apoptosis and is implicated as an important contributor to the pathogenesis of
      cardiac hypertrophy and heart failure. To examine the in vivo role of Raf-1 in
      the heart, we generated cardiac muscle-specific Raf-1-knockout (Raf CKO) mice
      with Cre-loxP-mediated recombination. The mice demonstrated left ventricular
      systolic dysfunction and heart dilatation without cardiac hypertrophy or
      lethality. The Raf CKO mice showed a significant increase in the number of
      apoptotic cardiomyocytes. The expression level and activation of MEK1/2 or ERK
      showed no difference, but the kinase activity of apoptosis signal-regulating
      kinase 1 (ASK1), JNK, or p38 increased significantly compared with that in
      controls. The ablation of ASK1 rescued heart dysfunction and dilatation as well
      as cardiac fibrosis. These results indicate that Raf-1 promotes cardiomyocyte
      survival through a MEK/ERK-independent mechanism.

PMID- 15467833
TI  - CEACAM1 modulates epidermal growth factor receptor--mediated cell proliferation.
AB  - Phosphorylation of the cell adhesion protein CEACAM1 increases insulin
      sensitivity and decreases insulin-dependent mitogenesis in vivo. Here we show
      that CEACAM1 is a substrate of the EGFR and that upon being phosphorylated,
      CEACAM1 reduces EGFR-mediated growth of transfected Cos-7 and MCF-7 cells in
      response to EGF. Using transgenic mice overexpressing a phosphorylation-defective
      CEACAM1 mutant in liver (L-SACC1), we show that the effect of CEACAM1 on EGF
      dependent cell proliferation is mediated by its ability to bind to and sequester
      Shc, thus uncoupling EGFR signaling from the ras/MAPK pathway. In L-SACC1 mice,
      we also show that impaired CEACAM1 phosphorylation leads to ligand-independent
      increase of EGFR-mediated cell proliferation. This appears to be secondary to
      visceral obesity and the metabolic syndrome, with increased levels of output of
      free fatty acids and heparin-binding EGF-like growth factor from the adipose
      tissue of the mice. Thus, L-SACC1 mice provide a model for the mechanistic link
      between increased cell proliferation in states of impaired metabolism and
      visceral obesity.

PMID- 15467834
TI  - High-level beta-globin expression and preferred intragenic integration after
      lentiviral transduction of human cord blood stem cells.
AB  - Transplantation of genetically corrected autologous hematopoietic stem cells is
      an attractive approach for the cure of sickle-cell disease and beta-thalassemia.
      Here, we infected human cord blood cells with a self-inactivating lentiviral
      vector encoding an anti-sickling betaA-T87Q-globin transgene and analyzed the
      transduced progeny produced over a 6-month period after transplantation of the
      infected cells directly into sublethally irradiated NOD/LtSz-scid/scid mice.
      Approximately half of the human erythroid and myeloid progenitors regenerated in
      the mice containing the transgene, and erythroid cells derived in vitro from
      these in vivo-regenerated cells produced high levels of betaA-T87Q-globin
      protein. Linker-mediated PCR analysis identified multiple transgene-positive
      clones in all mice analyzed with 2.1 +/- 0.1 integrated proviral copies per cell.
      Genomic sequencing of vector-containing fragments showed that 86% of the proviral
      inserts had occurred within genes, including several genes implicated in human
      leukemia. These findings indicate effective transduction of very primitive human
      cord blood cells with a candidate therapeutic lentiviral vector resulting in the
      long-term and robust, erythroid-specific production of therapeutically relevant
      levels of beta-globin protein. However, the frequency of proviral integration
      within genes that regulate hematopoiesis points to a need for additional safety
      modifications.

PMID- 15467835
TI  - Beta cell replication is the primary mechanism for maintaining postnatal beta
      cell mass.
AB  - The endocrine pancreas undergoes major remodeling during neonatal development
      when replication of differentiated beta cells is the major mechanism by which
      beta cell mass is regulated. The molecular mechanisms that govern the replication
      of terminally differentiated beta cells are unclear. We show that during neonatal
      development, cyclin D2 expression in the endocrine pancreas coincides with the
      replication of endocrine cells and a massive increase in islet mass. Using cyclin
      D2-/- mice, we demonstrate that cyclin D2 is required for the replication of
      endocrine cells but is expendable for exocrine and ductal cell replication. As a
      result, 14-day-old cyclin D2-/- mice display dramatically smaller islets and a 4
      fold reduction in beta cell mass in comparison to their WT littermates.
      Consistent with these morphological findings, the cyclin D2-/- mice are glucose
      intolerant. These results suggest that cyclin D2 plays a key role in regulating
      the transition of beta cells from quiescence to replication and may provide a
      target for the development of therapeutic strategies to induce expansion and/or
      regeneration of beta cells.

PMID- 15467837
TI  - Costimulation controls diabetes by altering the balance of pathogenic and
      regulatory T cells.
AB  - The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse
      results from a breakdown in tolerance to pancreatic islet antigens. CD28-B7 and
      CD40 ligand-CD40 (CD40L-CD40) costimulatory pathways affect the development of
      disease and are promising therapeutic targets. Indeed, it was shown previously
      that diabetes fails to develop in NOD-B7-2-/- and NOD-CD40L-/- mice. In this
      study, we examined the relative role of these 2 costimulatory pathways in the
      balance of autoimmunity versus regulation in NOD mice. We demonstrate that
      initiation but not effector function of autoreactive T cells was defective in NOD
      B7-2-/- mice. Moreover, the residual proliferation of the autoreactive cells was
      effectively controlled by CD28-dependent CD4+CD25+ regulatory T cells (Treg's),
      as depletion of Treg's partially restored proliferation of autoreactive T cells
      and resulted in diabetes in an adoptive-transfer model. Similarly, disruption of
      the CD28-B7 pathway and subsequent Treg deletion restored autoimmunity in NOD
      CD40L-/- mice. These results demonstrate that development of diabetes is
      dependent on a balance of pathogenic and regulatory T cells that is controlled by
      costimulatory signals. Thus, elimination of Treg's results in diabetes even in
      the absence of costimulation, which suggests a need for alternative strategies
      for immunotherapeutic approaches.

PMID- 15467836
TI  - Prevention of type 1 diabetes by gene therapy.
AB  - The autoimmune disease type 1 diabetes in humans and NOD mice is determined by
      multiple genetic factors, among the strongest of which is the inheritance of
      diabetes-permissive MHC class II alleles associated with susceptibility to
      disease. Here we examined whether expression of MHC class II alleles associated
      with resistance to disease could be used to prevent the occurrence of diabetes.
      Expression of diabetes-resistant MHC class II I-Abeta chain molecules in NOD mice
      following retroviral transduction of autologous bone marrow hematopoietic stem
      cells prevented the development of autoreactive T cells by intrathymic deletion
      and protected the mice from the development of insulitis and diabetes. These data
      suggest that type 1 diabetes could be prevented in individuals expressing MHC
      alleles associated with susceptibility to disease by restoration of protective
      MHC class II expression through genetic engineering of hematopoietic stem cells.

PMID- 15467838
TI  - Kinetics of protective antibodies are determined by the viral surface antigen.
AB  - Delayed and weak virus neutralizing antibody (nAb) responses represent a hallmark
      correlating not only with the establishment of persistent infection but also with
      unsuccessful vaccine development. Using a reverse genetic approach, we evaluated
      possible underlying mechanisms in 2 widely studied viral infection models.
      Swapping the glycoproteins (GPs) of lymphocytic choriomeningitis virus (LCMV,
      naturally persisting, noncytolytic, inefficient nAb inducer) and vesicular
      stomatitis virus (VSV, nonpersisting, cytolytic, potent nAb inducer) transferred
      the only target of nAb's from either virus to the other. We analyzed the nAb
      response to each of the 2 recombinant and parent viruses in infected mice and
      found that nAb kinetics were solely determined by the viral surface GP and not by
      the virus backbone. Moreover, the slowly and poorly nAb-triggering LCMV virion
      was a potent immunogenic matrix for the more antigenic VSV-GP. These findings
      indicate that the viral GP determines nAb kinetics largely independently of the
      specific viral infection context. They further suggest that structural features
      of viral GPs or coevolutionary adaptation of the virus's GP to the host's naive B
      cell repertoire, or both, may critically limit nAb kinetics and improvement of
      vaccine efficacy.

PMID- 15467840
TI  - Hierarchical self-assembly in polymeric complexes: towards functional materials.
AB  - Combination of self-assembly at different length scales leads to structural
      hierarchies. It offers rich possibilities to construct nanostructured matter,
      nanoscale parts, and switching (responsive) properties based on the phase
      transitions of the self-assembled structures. Complexation of oligomeric
      amphiphiles to polymers using ionic interactions, coordination, or hydrogen
      bonding leads to polymeric comb-shaped supramolecules (complexes), which self
      assemble at a length scale of a few nm. Self-assembly at an order of magnitude
      larger length scale is provided by block copolymers, and combination of the
      latter two concepts leads to structural hierarchies. They provide e.g. templates
      for mesoporous materials and nano-objects, and allow switching conductivity and
      switching optical properties. Structural hierarchies are also observed by
      complexing moderately monodisperse polymeric rods with amphiphiles. Finally, self
      assembly at even a larger length scale upon using colloidal particles may be
      combined to the above structures, as encouraged by recent observations.

PMID- 15467839
TI  - Differential subunit composition of the G protein-activated inward-rectifier
      potassium channel during cardiac development.
AB  - Parasympathetic slowing of the heart rate is predominantly mediated by
      acetylcholine-dependent activation of the G protein-gated potassium (K+) channel
      (IK,ACh). This channel is composed of 2 inward-rectifier K+ (Kir) channel
      subunits, Kir3.1 and Kir3.4, that display distinct functional properties. Here we
      show that subunit composition of IK,ACh changes during embryonic development. At
      early stages, IK,ACh is primarily formed by Kir3.1, while in late embryonic and
      adult cells, Kir3.4 is the predominant subunit. This change in subunit
      composition results in reduced rectification of IK,ACh, allowing for marked K+
      currents over the whole physiological voltage range. As a consequence, IK,ACh is
      able to generate the membrane hyperpolarization that underlies the strong
      negative chronotropy occurring in late- but not early-stage atrial cardiomyocytes
      upon application of muscarinic agonists. Both strong negative chronotropy and
      membrane hyperpolarization can be induced in early-stage cardiomyocytes by viral
      overexpression of the mildly rectifying Kir3.4 subunit. Thus, a switch in subunit
      composition is used to adopt IK,ACh to its functional role in adult
      cardiomyocytes.

PMID- 15467842
TI  - The mechanism of the oxidative addition of aryl halides to Pd-catalysts: a DFT
      investigation.
AB  - Based on DFT calculations, a new mechanism for the oxidative addition of aryl
      halides to Pd-catalysts is presented. The key intermediate is an anionic Pd
      species in which the aryl halide coordinates to the palladium via the halide
      atom.

PMID- 15467841
TI  - Synthesis of the ABCD and ABCDE ring systems of azaspiracid-1.
AB  - The efficient syntheses of the ABCD ring system of the originally proposed
      structure of azaspiracid-1 and the ABCDE ring system of the revised structure of
      azaspiracid-1 containing the correct stereochemistry at C(6), C(10), C(13),
      C(14), C(16), C(17), C(19), C(21), C(22), C(24) and C(25) have been achieved.

PMID- 15467843
TI  - A very large Rh-Rh bond shortening on excitation of the [Rh2(1,8-diisocyano-p
      menthane)4]2+ ion by time-resolved synchrotron X-ray diffraction.
AB  - A very large Rh-Rh contraction of approximately 0.85 A occurs on excitation of
      the [Rh(2)(1,8-diisocyano-p-menthane)(4)](2+) ion to its triplet state.

PMID- 15467844
TI  - Racemic D,L-asparagine causes enantiomeric excess of other coexisting racemic D,L
      amino acids during recrystallization: a hypothesis accounting for the origin of L
      amino acids in the biosphere.
AB  - When recrystallizations were performed using a mixture of 12 D,L-amino acids
      (alanine, aspartic acid, arginine, glutamic acid, glutamine, histidine, leucine,
      methionine, serine, valine, phenylalanine, and tyrosine) with excess D,L
      asparagine, all amino acids with the same configuration as asparagine were
      preferentially co-crystallized, indicating that it is the nature of a mixture of
      racemic amino acids to produce a spontaneous high enantiomeric excess.

PMID- 15467845
TI  - A thermally stable nanoporous nickel 5-sulfoisophthalate; crystal structure and
      adsorption properties.
AB  - A 3D nanoporous nickel 5-sulfoisophthlate coordination polymer with a high
      surface area (>700 m(2) g(-1)) has been synthesized hydrothermally and studied
      using single crystal and variable-temperature powder XRD, TGA, and BET
      porosimetry.

PMID- 15467846
TI  - Single-walled carbon nanotubes acquire a specific lectin-affinity through
      supramolecular wrapping with lactose-appended schizophyllan.
AB  - Single-walled carbon nanotubes can be entrapped within a helical superstructure
      composed of schizophyllan bearing lactoside-appendages to show an excellent water
      solubility as well as a specific lectin-affinity.

PMID- 15467847
TI  - Motion of methanol adsorbed in porous coordination polymer with paramagnetic
      metal ions.
AB  - Molecular motions of methanol adsorbed in 1D nanochannels of pillared-layer
      coordination polymer with paramagnetic metal ions have been studied by (2)H NMR
      together with X-ray crystallography.

PMID- 15467848
TI  - Preparation of poly(3,4-ethylenedioxythiophene)(PEDOT) coated silica core-shell
      particles and PEDOT hollow particles.
AB  - Nanometre-sized PEDOT-silica core-shell particles were synthesized and self
      assembled into crystalline colloidal arrays with a reflection peak in the visible
      region; these particles were also etched with hydrofluoric acid to produce hollow
      PEDOT particles.

PMID- 15467849
TI  - Secondary coordination sphere controlled reversible geometry reorganisations in
      copper(II) complexes.
AB  - Reversible geometry reorganisations are demonstrated by cis-3,5-diamino-trans
      hydroxycyclohexane (cis,trans-DAHC) copper(ii) fluoride complexes, with the
      concentration of water in the mother liquor controlling interconversion between
      blue crystals of 5-coordinate syn-[Cu(DAHC)(2)F](F).2CH(3)OH.H(2)O and red
      crystals of 4-coordinate anti-[Cu(DAHC)(2)](F)(2).2H(2)O.

PMID- 15467850
TI  - Assembly of large simple 1D and rare polycatenated 3D molecular ladders from T
      shaped building blocks containing a new, long N,N'-bidentate ligand.
AB  - Molecular ladders [Co(2)(nbpy4)(3)(NO(3))(4)]*solvents and
      [Cd(2)(nbpy4)(3)(NO(3))(4)](nbpy4 =N,N'-bis-(4-pyridinylmethylene)-1,5
      naphthalenediamine) were synthesized via self-assembly; the former is a large,
      simple, noninterpenetrated 1D ladder that contains guest solvent molecules
      between the rungs, while the latter exists as 1D ladders in a rare four-fold
      interlocked 3D structure.

PMID- 15467851
TI  - Synthesis and reactivity of triethylborane adduct of N-heterocyclic carbene:
      versatile synthons for synthesis of N-heterocyclic carbene complexes.
AB  - The reaction of an imidazolium salt with LiBEt(3)H afforded triethylborane adduct
      of imidazol-2-ylidene, which can act as a carbene precursor for the synthesis of
      a transition metal complex as well as a main group element complex.

PMID- 15467852
TI  - A new packing motif for para-sulfonatocalix[4]arene: the solid state structure of
      the para-sulfonatocalix[4]arene D-arginine complex.
AB  - The solid-state structure of the complex of para-sulfonatocalix[4]arene with d
      arginine, contains a water channel diagonal to a zigzag bilayer of the host,
      within the bilayer six crystallographically independent molecules of arginine are
      present, four being included in the calix cavities.

PMID- 15467853
TI  - Synthesis and characterization of electron-rich nickel tris-carbene complexes.
AB  - The synthesis and characterization of the first nickel(0)/(i) tris-carbene
      complex with a nitrogen anchored tripodal N-heterocyclic carbene ligand are
      described.

PMID- 15467854
TI  - Isolation and structural characterization of an optically active intermediate in
      the oxidative addition of methyl iodide on a rhodium(I) centre.
AB  - The optically pure cationic complex (S,S(Rh))-[Rh(eta5-C(5)H(4)CH(2)CH(Ph)PPh(2)
      kappaP)(eta2-CH(2)CH(2))(CH(3))][I] is the first example of a key intermediate in
      the oxidative addition reaction of methyl iodide on a rhodium(I) centre which has
      been structurally characterized by X-ray diffraction.

PMID- 15467855
TI  - Nanoporosity of an interpenetrated NbO-type molecular framework studied by single
      crystal X-ray diffraction.
AB  - The molecular framework [Fe(NCS)(2)(tmbpz)(2)](tmbpz = 3,3',5,5'-tetramethyl-4,4'
      bipyrazolyl) consists of a robust doubly interpenetrated NbO-type network that
      remains stable on the removal of solvent guest molecules.

PMID- 15467856
TI  - Water-in-water mesophases for templating inorganics.
AB  - A water-in-water mesophase that contains only hydrophilic domains is reported for
      the first time; the mesophase templates highly porous calcium phosphate.

PMID- 15467857
TI  - Bis(diethylamino)carbene and the mechanism of dimerisation for simple
      diaminocarbenes.
AB  - Bis(diethylamino)carbene is kinetically stable to dimerization in THF at ambient
      temperature; dimer formed during carbene generation arises from reaction of the
      carbene with the precursor formamidinium ion; this is probably the commonest
      route to tetraaminoethene dimers, and in a related case the intermediate
      protonated tetraaminoethene can be observed by NMR.

PMID- 15467858
TI  - The surprisingly beneficial effect of soft donors on the performance of early
      transition metal olefin polymerisation catalysts.
AB  - Group 4 metal complexes containing phenoxy-amide ligands bearing soft pendant
      donors are shown to give more highly active ethylene polymerisation catalysts
      than counterparts containing hard donors or systems without a pendant donor.

PMID- 15467859
TI  - Unexpected oxidative C-C cleavage in the metallation of 2-substituted imidazolium
      salts to give N-heterocyclic carbene complexes.
AB  - Imidazolium salts blocked at C2 with methyl or benzyl groups unexpectedly react
      with silver oxide to give N-heterocyclic carbene complexes of silver via an
      oxidative carbon-carbon bond cleavage.

PMID- 15467860
TI  - Estimates of internal energies of vaporisation of some room temperature ionic
      liquids.
AB  - Systematic variation in the bimolecular rate constant, k(q), for the reaction of
      singlet oxygen and 1,4-dimethylnaphthalene has led to estimates of the Hildebrand
      solubility parameter, cohesive pressures and internal energies of vaporisation of
      some room temperature ionic liquids.

PMID- 15467861
TI  - First lanthanide dipolar complexes for second-order nonlinear optics.
AB  - New push-pull NLO-phores based on lanthanide complexes (Ln = La, Gd, Dy, Yb)
      featuring an annelated dibutylaminophenyl functionalised terpyridyl ligand have
      been synthesised and shown to exhibit large first-order hyperpolarizability.

PMID- 15467862
TI  - Microemulsion-based synthesis of stacked calcium carbonate (calcite)
      superstructures.
AB  - Synthesis of calcium carbonate in water-in-oil microemulsions results in the
      spontaneous formation of stacked superstructures of 20 nm-thick pseudo-hexagonal
      calcite plates in crystallographic register.

PMID- 15467863
TI  - A direct synthetic approach to vanadium pentoxide nanofibres modified with silver
      nanoparticles.
AB  - Small amounts of silver ions have been found to significantly enhance the growth
      rate of vanadium pentoxide (V(2)O(5)) nanofibres in aqueous solution at room
      temperature, yielding fibres with lengths of several micrometers within a few
      days; the V(2)O(5) fibres are decorated with silver nanoparticles with sizes in
      the range of 5-15 nm, which opens perspectives for applications in chemical
      sensors.

PMID- 15467864
TI  - Polymer-in-salt like conduction behavior of small-molecule electrolytes.
AB  - Abnormal salt content dependence of conductivity is observed in solid
      electrolytes exclusively composed of small molecules of 3-hydroxypropionitrile
      (HPN) and lithium iodide (LiI) induced by reinforced hydrogen bonding and
      formation of ionic clusters at high salt content.

PMID- 15467865
TI  - Hierachically porous nanocrystalline cobalt oxide monoliths through nanocasting.
AB  - Nanocrystalline cobalt oxide, Co(3)O(4), monoliths exhibiting hierarchical
      bimoidal porosity have been prepared by nanocasting of porous silica monoliths.

PMID- 15467866
TI  - Carbon nanotube/poly(2,4-hexadiyne-1,6-diol) nanocomposites prepared with the aid
      of supercritical CO2.
AB  - Poly(2,4-hexadiyne-1,6-diol)(poly(HDiD)) was coated on the outer walls of carbon
      nanotubes (CNTs) with the aid of supercritical CO(2), resulting in poly(HDiD)/CNT
      nanocomposites, which possess optical properties originated from poly(HDiD).

PMID- 15467867
TI  - Water reduction and oxidation on Pt-Ru/Y2Ta2O5N2 catalyst under visible light
      irradiation.
AB  - Y(2)Ta(2)O(5)N(2) is presented as a novel photocatalyst with high activity for
      water splitting under visible-light irradiation in the presence of appropriate
      sacrificial reagents; the activity for reduction to H(2) is increased by the
      incorporation of Pt or Ru as a co-catalyst, with a significant increase in
      production efficiency when both Pt and Ru are present.

PMID- 15467868
TI  - Ionic hydrogenation of C-20, 22-ketene dithioacetal: stereoselective synthesis of
      steroidal C (20R) aldehydes.
AB  - Homologation of 16-dehydropregnenolone acetate leads to excellent
      stereocontrolled synthesis of unnatural C (20R) aldehydes and through compound .

PMID- 15467869
TI  - Facile deposition of copper-doped diamond-like carbon nanocomposite films by a
      liquid-phase electrochemical route.
AB  - Copper-doped diamond-like carbon nanocomposite films have been facilely deposited
      by a liquid-phase electrochemical route from an acetonitrile solution of
      [Cu(CH(3)CN)(4)]ClO(4).

PMID- 15467870
TI  - Efficient boron removal by using mesoporous matrices grafted with saccharides.
AB  - Highly efficient boron removal from water was achieved by using mesoporous silica
      materials functionalised with saccharides.

PMID- 15467871
TI  - Redox couples in the selective catalytic reduction of NOx with hydrocarbons over
      Co-ZSM-5 and Ni-ZSM-5 catalysts: an FT-IR study.
AB  - On the basis of IR spectroscopy studies it is concluded that the redox couples
      Co(2+)/Co(+) and Ni(2+)/Ni(+) operate in the selective catalytic reduction of
      nitrogen oxides with hydrocarbons over Co-ZSM-5 and Ni-ZSM-5.

PMID- 15467872
TI  - A simple approach to mesoporous fibrous titania from potassium dititanate.
AB  - A new approach is developed to synthesize mesoporous fibrous titania from the
      sintered product of K(2)Ti(2)O(5), which involves a novel hydrolytic reaction for
      the formation of potassium-rich nanophase and the generation of an amorphous
      intermediate.

PMID- 15467873
TI  - Direct probe electrospray (and nanospray) ionization mass spectrometry of neat
      ionic liquids.
AB  - Electrospray ionization mass spectrometry of neat ionic liquids does not require
      continuous sample injection and the presence of a molecular solvent facilitates
      analysis of the ionic liquid itself and dissolved analytes.

PMID- 15467874
TI  - Imidazolidinium-based robust crypt with unique selectivity for fluoride anion.
AB  - A new imidazolidinium based receptor exhibiting unique affinity and high
      selectivity for fluoride anion through steric requirements and the cooperativity
      of multiple intramolecular binding, has been designed, synthesized and
      structurally characterized.

PMID- 15467875
TI  - An analogue of adenine that forms an "A:T" base pair of comparable stability to
      G:C.
AB  - The heterocyclic base 7-aminopropargyl-7-deaza-2,6-diaminopurine (D) has been
      incorporated into oligodeoxynucleotides. D:T has similar thermodynamic stability
      to G:C and is a stable analogue of A:T.

PMID- 15467876
TI  - Hydrogen storage of metal nitride by a mechanochemical reaction.
AB  - Metal imides (Li(2)NH, CaNH), a metal amide (LiNH(2)) and metal hydrides (LiH,
      CaH(2)) were synthesized by ball milling of their respective metal nitrides
      (Li(3)N, Ca(3)N(2)) in a H(2) atmosphere at 1 MPa and at room temperature.

PMID- 15467877
TI  - Ultrastable complexes for in vivo use: a bifunctional chelator incorporating a
      cross-bridged macrocycle.
AB  - The synthesis, copper(II) complexation and biotin conjugation of a bifunctional
      chelator incorporating a cross-bridged macrocycle are described.

PMID- 15467878
TI  - Novel non-hydrolytic synthesis of a V2O5-TiO2 xerogel for the selective catalytic
      reduction of NOx by ammonia.
AB  - A vanadia-titania mesoporous xerogel (10.5 wt% V(2)O(5)) was prepared from
      chloride precursors using a one-step non-hydrolytic sol-gel route and subsequent
      drying at ambient pressure; after calcination at 773 K for 5 h no crystalline
      V(2)O(5) was detected and the resulting mixed oxide exhibited remarkable activity
      in the selective reduction of NO with NH(3).

PMID- 15467879
TI  - New crystalline forms of permethylated beta-cyclodextrin.
AB  - Two new crystalline forms of permethylated [small beta]-cyclodextrin are reported
      that contain methylglucose residues exclusively in the (4)C(1) conformation, in
      contrast to the known monohydrate, in which a single methylglucose residue adopts
      the (1)C(4) conformation.

PMID- 15467880
TI  - Unprecedented insertion reaction of a silylene into a B-B bond and generation of
      a novel borylsilyl anion by boron-metal exchange reaction of the resultant
      diborylsilane.
AB  - A kinetically stabilized diarylsilylene, Tbt(Mes)Si: (1, Tbt = 2,4,6
      tris[bis(trimethylsilyl)methyl]phenyl, Mes = mesityl), thermally generated from
      overcrowded disilene Tbt(Mes)Si=Si(Mes)Tbt (2) or stable silylene-isocyanide
      complex (3a), was found to insert into a B-B bond of bis(pinacolato)diboron,
      B2(pin)2 (4), and the boron-lithium exchange reaction of the resulting
      diborylsilane gave the first borylsilyl anion.

PMID- 15467881
TI  - Cyclic water pentamer in a tape-like structure.
AB  - A novel water tape consisting of fused cyclic water pentamers has been observed
      in a supramolecular compound.

PMID- 15467882
TI  - Photochemical polymerization of thiophene derivatives in aqueous solution.
AB  - A novel method of photochemical polymerization of thiophene derivatives in
      aqueous solution catalyzed by potassium dichromate and initiated by illumination
      is described.

PMID- 15467883
TI  - New Pb-Pb bonds: syntheses and molecular structures of hexabiphenyldiplumbane and
      tri(trisbiphenylplumbyl)plumbate.
AB  - Reaction of lead(II) chloride with biphenylmagnesium bromide yields Bp(3)Pb
      PbBp(3) and [(THF)(3)Mg(mu-Cl)(3)Mg(THF)(3)][Pb(PbBp(3))(3)](Bp = biphenyl),
      which, upon single crystal X-ray crystallographic analysis, reveals an
      interesting variation of Pb-Pb bond distances.

PMID- 15467884
TI  - A modular ditopic crown-shielded phosphate ion-pair receptor.
AB  - The synthesis of a modular hybrid receptor containing both an aza macrocycle and
      crown ether is described; a complete thermodynamic characterisation of the
      binding properties, in water, of the zinc(II) complex of the receptor towards
      phosphate is presented and the parameters are compared to those of the aza
      macrocycle precursor.

PMID- 15467885
TI  - The first samarium(II)-mediated aryl radical cyclisation onto an aromatic ring.
AB  - Intramolecular arylation of aryl radicals was mediated by SmI(2)/HMPA in the
      presence of i-PrOH to give spirocycles and/or reduced cine-cyclised products,
      while the reaction in the absence of i-PrOH gave the rearomatised fused rings.

PMID- 15467886
TI  - A supramolecular approach to the selective detection of dopamine in the presence
      of ascorbate.
AB  - Dopamine can be detected selectively in the presence of ascorbate at a gold
      electrode modified by a beta-cyclodextrin/thioctic acid mixed monolayer.

PMID- 15467887
TI  - High efficiency mer-iridium complexes for organic light-emitting diodes.
AB  - We have developed a new process at high vacuum (5 x 10(-5) Torr) and high
      temperature (300 degrees C) to produce meridional iridium complexes from the
      dimer; interestingly, mer-Ir(m-ppy)(3) overthrows the concept of poor efficiency
      and shows excellent efficiency which is almost equal to that of fac-Ir(ppy)(3),
      fac-Ir(m-ppy)(3) and (ppy)(2)Ir(acac).

PMID- 15467888
TI  - Unsaturated 1,2-amino alcohols and ethers from aziridines and organolithiums.
AB  - Organolithium-induced ring-opening of aziridines of 2,5-dihydrofuran (5 and 8)
      and 1,4-dimethoxybut-2-ene (16, 17 and 23) gives 3-substituted 2-aminobut-3-en-1
      ols 9-15 and amino ethers 18-20 and 24-26.

PMID- 15467889
TI  - Synthesis and in vitro photodynamic activity of new hexadeca-carboxy
      phthalocyanines.
AB  - Two new hexadeca-carboxy phthalocyanines have been synthesised and evaluated for
      their photodynamic activities; the zinc(II) analogue exhibits a high class-A
      scavenger-receptor mediated photocytotoxicity towards the J774 murine macrophage
      cell line.

PMID- 15467890
TI  - Novel Pt/CeO2/C catalysts for electrooxidation of alcohols in alkaline media.
AB  - Electrochemical oxidation of methanol, ethanol, glycerol and ethylene glycol (EG)
      on novel Pt-CeO(2)/C catalysts in alkaline media has been studied and shows an
      improved performance in terms of the electrode activity and the poisoning
      resistance.

PMID- 15467891
TI  - The anion sequence in the phase transformation of mesostructures templated by non
      ionic block copolymers.
AB  - A p6m to Ia3d mesophase evolution is achieved by simply adjusting the acidity
      and/or anion species in the presence of block copolymers; the unusual anion
      sequence that affects the phase behavior of block copolymer templated
      mesostructured solids is revealed to be SO(4)(2-)(HSO(4)(-)) > NO(3)(-) > Br(-) >
      Cl(-).

PMID- 15467892
TI  - Paracetamol (acetaminophen) and warfarin interaction: unraveling the pivotal role
      of the vitamin K cycle.

PMID- 15467893
TI  - Further complexities in diagnosing acquired thrombocytopenia: unexpected
      parallels between antibody-mediated delayed thrombocytopenia with abciximab and
      heparin induced thrombocytopenia.

PMID- 15467894
TI  - New insights into paediatric haemostasis: thrombosis and bleeding issues.

PMID- 15467895
TI  - Thrombophilia and pregnancy complications.
AB  - The implications of currently available data on the association of gestational
      vascular complications with thrombophilia are presented in this consensus report.
      Screening is recommended for women with the following previous complications:
      fetal loss including three or more first trimester loss, two or more second
      trimester loss, or any stillbirth; early, severe or recurrent preeclampsia and
      severe intrauterine growth restriction. Maternal antithrombotic therapy is
      currently evaluated in women with thrombophilia and previous complications.

PMID- 15467896
TI  - Increased shear stress- and ristocetin-induced binding of von Willebrand factor
      to platelets in cord compared with adult plasma.
AB  - Multiple indications do exist that the extensive neonatal platelet adhesion and
      aggregation, and the shorter closure time of neonatal compared with adult whole
      blood in the platelet function analyzer 100 are attributable to the physiological
      high plasma concentrations and high concentrations of unusually large von
      Willebrand factor (vWf) multimers in neonates. However, to date the direct
      experimental evidence is lacking. Therefore, we compared in the present study the
      ability of neonatal vWf to bind to platelets to that of adult vWf. Platelet-poor
      plasma of neonatal or adult origin, containing antibody-stained vWf, was
      incubated with neonatal or adult platelet suspension. Subsequently, vWf-platelet
      interaction was induced by exposing the mixture to shear stress by means of a
      cone/plate measuring system or by incubating the mixture with ristocetin.
      Finally, samples were analyzed in a FACScan flow cytometer. Detected fluorescence
      intensities directly correlate with the amount of vWf attached to the platelet
      surface. We found that significantly higher amounts of neonatal vWf were attached
      to platelets in the presence of shear stress or ristocetin. This efficient
      neonatal vWf-platelet interaction is an effect intrinsic to the neonatal vWf, and
      not to the neonatal platelet: the amount of neonatal vWf attached to neonatal
      platelets was not different from the amount of neonatal vWf attached to adult
      platelets. Furthermore, decreasing the vWf content in cord plasma to adult level
      resulted in significantly suppressed vWf-platelet attachment in the presence of
      ristocetin, indicating that the high neonatal vWf level contributes to the
      efficient vWf-platelet binding in neonates.

PMID- 15467897
TI  - Development of selected coagulation factors and anticoagulants in preterm infants
      by the age of six months.
AB  - The development of the coagulation and anticoagulation system in preterm infants
      was assessed, with special emphasis on extremely low birth weight (ELBW) infants
      and haemorrhagic or other complications after birth. Coagulation factors II
      (prothrombin), V (FV), VII (FVII) and X (FX) were analysed at birth and at a
      corrected age of six months. In addition, antithrombin (AT), protein C (PC) and
      protein S (PS) were measured at six months, and DNA samples were tested for
      Factor V Leiden (R506Q). Eighty-two infants, with a median gestational age (GA)
      of 32 weeks (range 24-36) and a median birth weight of 1562 g (range 695-3520),
      were studied. Fifteen of these were ELBW infants (range 695-1000g). Prothrombin,
      FV, FVII and FX reached healthy term six-month-old infant activity levels.
      Prothrombin and FX did not reach adult values; median activity levels remained at
      82% and 78%, respectively. During the follow up, the FV and FVII levels of the
      ELBW infants (GA 24-27 weeks) increased more than those of the preterm infants
      born with higher GA (p < 0.001). At birth, prothrombin correlated significantly
      with FV, FVII and FX (p < 0.001). FVII at birth and at six months correlated
      significantly with PC (p = 0.021 and p = 0.009, respectively). These findings
      indicate that the gain in the coagulation factor concentrations in infancy is
      greatest in infants with the lowest GA at birth. Interesting new inter-relations
      of coagulation factor and physiological anticoagulant levels may indicate that
      there are still unrecognised pathways in the function of newborn haemostasis.

PMID- 15467898
TI  - Arterial ischaemic stroke in children. Review of the literature and strategies
      for future stroke studies.
AB  - Conditions associated with arterial ischaemic stroke in children include a great
      variety of diseases and triggers such as congenital heart malformations, sickle
      cell disease, infections and vasculopathies, although up to 50% are cryptogenic.
      An abnormal vascular status can be demonstrated by vascular imaging in up to 80%
      of children with ischaemic stroke, and case control studies demonstrate an
      association between ischaemic stroke in children and hereditary prothrombotic
      risk factors and infections such as Varicella. Conventional risk factors such as
      hypertension and dyslipidaemia may also play a role, and most children have
      several potential triggers rather than one single cause. This review focuses on
      clinical presentations, imaging methods, stroke subtypes, underlying conditions
      including prothrombotic risk factors, outcome and recurrence. Although data from
      randomised controlled trials, on which clinical practice might be based, are
      sparse, therapeutic approaches and future research directions are discussed.

PMID- 15467899
TI  - Total tissue factor pathway inhibitor is an independent risk factor for
      symptomatic paediatric venous thromboembolism and stroke.
AB  - Tissue factor pathway inhibitor (TFPI) plays an important role in inhibiting
      tissue factor-induced coagulation by a factor Xadependent pathway of the
      activated tissue-factor VIIa complex. Decreased values of the latter inhibitor
      have been recently reported in adult patients with venous thrombosis (VT) or
      ischaemic stroke (IS). The present case-control study was therefore performed to
      evaluate whether a decreased TFPI concentration is also involved in paediatric
      symptomatic thromboembolism (ST). Total TFPI concentrations were measured along
      with established prothrombotic risk factors six to twelve months after the acute
      thrombotic onset in 144 Caucasian children aged 0.6 to 18 years (VT: n=80; IS:
      n=64). The cut-off values defined as age-dependent 10(th) percentiles were
      obtained from 244 healthy controls. Median (range) values of TFPI were
      significantly lower in patients compared with control subjects [50.0(20.0-132.3)
      ng/ml vs. 59.5(25.4-117.4) ng/ml; p-value < 0.0001]. In addition, 42 of the 144
      patients (29.2%) compared with 25 of the 244 controls (10.2%) showed TFPI
      concentrations below the 10(th) age-dependent percentiles. Compared to baseline
      values 78.6% of children with total TFPI Ag < 10(th) percentiles showed a low
      response to enoxaparin administration, whereas in children with normal baseline
      TFPI values 30% show a low TFPI release (p = 0.007). Multivariate analysis
      adjusted for the presence of established prothrombotic risk factors showed a
      significantly increased odds ratio (OR) and 95% confidence interval (CI) for
      patients with ST [OR/CI: 3.8/2.2-6.6; p < 0.0001]. Data shown here give evidence
      that total TFPI concentrations below the 10(th) age-dependent percentiles
      independently increase the risk of ST in Caucasian children 3.8-fold.

PMID- 15467901
TI  - Systemic thromboembolism in children. Data from the 1-800-NO-CLOTS Consultation
      Service.
AB  - Thromboembolism (TE) has recently been recognized as a clinical entity in
      children. Determining the clinical characteristics of pediatric TE is an
      important first step in dealing with this new disorder. The paper summarizes 1776
      consecutive children with systemic TE referred to 1-800-NO-CLOTS telephone
      consultation service. 1-800-NO-CLOTS is a free consultation service for
      clinicians managing pediatric TE. Patient information was collected immediately
      using standardized forms. In children with systemic TE, infants under one year of
      age (47%) including neonates (26%) represented the largest distinct pediatric age
      group. Age-related differences were seen in TE locations, associated conditions,
      and risk factors. However, venous TE was the most frequent manifestation (74%).
      Neonates and children with cardiac disorders were more likely to have an arterial
      TE than a venous TE Beyond the neonatal period, venous TE associated with a
      central line is more likely to occur than arterial TE. Children with ALL were 5.7
      times more likely to have a venous TE than an arterial TE. TE were infrequent in
      otherwise healthy children with 90% of children having at least one risk factor.
      Central catheters were the single most common risk factor associated with TE,
      present in 2/3 of children. Ultrasound was most frequently employed for diagnosis
      of TE. Finally, there was marked heterogeneity in treatment of children with TE.
      In children, neonates form the largest single group with TE. TE usually occur
      only in the presence of one or more risk factors with catheters being the single
      most important factor.

PMID- 15467900
TI  - Paediatric cerebral sinus vein thrombosis. A multi-center, case-controlled study.
AB  - The etiology and pathophysiology of cerebral sinus venous thrombosis (CSVT) in
      the paediatric population is still poorly understood, and the role of
      thrombophilic risk factors remains to be elucidated. In our multi-center case
      controlled study we studied 46 patients with CSVT diagnosed from April 1996 to
      December 2003, consecutively referred for thrombophilia work-up. The results of
      thrombophilia screen were compared to 112 healthy paediatric controls.
      Anticoagulant therapy was applied according to treating physicians' decisions,
      and all cases were prospectively followed for a median of 4.1 years. Of 46
      children, 8 had CSVT diagnosed in the neonatal period and therefore were analyzed
      separately. The prevalence of single thrombophilia markers and combinations of
      thrombophilic risk factors were similar among cases and controls. Among children
      with CSVT co-morbid systemic illness was present in most patients at diagnosis.
      Seven out of 8 children with idiopathic CSVT had thrombophilic risk factors as
      compared to 31/38 patients with co-morbid conditions. Anticoagulation was
      initiated in most patients, 11/46 patients continued therapy for a total of one
      year or more post event. Neither clinical presentation nor initial treatment
      decisions were affected by presence of thrombophilic risk factors in our study
      group. Thrombophilia prevalence was not increased in children with CSVT as
      compared to controls, however thrombophilia was more frequent among children with
      idiopathic CSVT. Thus, those selected patients would benefit most from
      thrombophilia work-up, required for long-term therapy considerations.

PMID- 15467902
TI  - A case series of 72 neonates with renal vein thrombosis. Data from the 1-800-NO
      CLOTS Registry.
AB  - Neonatal renal vein thrombosis (RVT) is a well-recognized clinical entity which
      is associated with serious morbidity. However, current information regarding RVT
      has been restricted to case reports and small case series. In this study, it was
      our objective to describe patient demographics, clinical presentation, location
      and risk factors of RVT. For our study design, we looked at a case series of 72
      neonates with RVT referred to the 1-800-NO-CLOTS consultation service between
      9/1996 and 8/2001. Data on age, gender, associated conditions, prothrombotic
      disorders, family history, location of the thrombosis, diagnostic techniques, and
      treatment were prospectively recorded using a standardized form. Our results show
      that RVT affected males (65%, CI 52-76%) significantly more often than females
      (35%, CI 24-48%). Median age at presentation was 2 days (0-21 days). RVT was
      unilateral in 72% (left side: 67%,CI 49-81%; right side: 33%, CI 19-51%), and
      bilateral in 28%. The majority (83%) had at least one associated condition:
      Prematurity (54%), central venous lines (17%), a diabetic mother (13%), asphyxia
      (6%), infections (6%). Prothrombotic testing was performed in 21 neonates.
      Activated protein C resistance was found in 8 children (38%), other defects in
      three. This is the largest case series of neonatal RVT to date. Data from the
      study show that i) male infants are affected twice as often as females and ii)
      there appears to be a left-sided predominance of neonatal RVT. Neonatal RVT is
      only infrequently associated with the presence of a catheter as compared to
      thrombosis at other sites. The majority of infants have associated conditions
      with prematurity being most frequent. A small subset of neonates were screened
      for prothrombotic abnormalities and 50% of the children screened were positive.

PMID- 15467903
TI  - Point of care monitoring of oral anticoagulant therapy in children: comparison of
      CoaguChek Plus and Thrombotest methods with venous international normalised
      ratio.
AB  - This paper reports the outcome of a research protocol aimed at optimising
      warfarin monitoring in a tertiary pediatric centre. The Thrombotest INR was the
      standard monitoring test employed to manage oral anticoagulant therapy in
      children at the Royal Children's Hospital (RCH), Melbourne. This study compares
      the results of this standard method to the novel CoaguChek INR monitor and the
      "gold standard" technique of venous INR sampling. The objectives were to
      determine 1) if point-of-care techniques of measuring the INR (Thrombotest and
      CoaguChek) are accurate and reliable compared to INR results obtained from venous
      sampling, processed in an accredited laboratory, and 2) if INR results generated
      by POC devices can be safely used to manage oral anticoagulant therapy in
      children. 18 children (10 females and 8 males) participated in the study. Ages
      ranged from 9 months to 21 years (Mean 11.9 years; SD 5.03 years). The agreement
      between CoaguChek and venous INR measurements (r = 0.885) was shown to be higher
      compared to Thrombotest and venous INR (r = 0.700). Compared to the venous INR,
      values obtained with Coaguchek and Thrombotest crossed into or out of the
      therapeutic range in 25% and 36% of cases respectively. In 88% of the CoaguChek
      cases and 57% Thrombotest cases, the difference from the venous result was less
      than 0.5. The CoaguChek method of INR monitoring is a more accurate and reliable
      method compared to Thrombotest, in the pediatric population tested, and can be
      safely used to manage oral anticoagulant therapy in children.

PMID- 15467904
TI  - The use of rFVIIa in non-haemophilia bleeding conditions in paediatrics. A
      systematic review.
AB  - From its original envisioned use in patients with hemophilia and inhibitors,
      recombinant factor VIIa has been increasingly used in a variety of non-hemophilia
      bleeding/hemorrhagic situations with great efficacy. Most of the reported work
      has been in adult patients. This paper sets out to review its use in the
      pediatric non-hemophilia patients and the varied conditions it has been tried and
      used. Most of the published literature has shown that this agent is efficacious,
      safe and can be used as an adjunctive measure in the achievement of hemostasis.
      However, most of the published work is mainly anecdotal, case reports or small
      series. Randomized trials in children are eagerly awaited.

PMID- 15467905
TI  - Low molecular weight heparin for the prophylaxis of thromboembolism in women with
      prosthetic mechanical heart valves during pregnancy.
AB  - Increased thromboembolic events occur in women with mechanical prosthetic valves
      during pregnancy, and selecting an effective and safe anticoagulant is still a
      challenge. Low molecular weight heparin (LMWH) is a promising alternative, but a
      recent warning and label change about its use in patients with mechanical
      prosthetic valves has caused confusion among physicians. The aim of the present
      study was to review the risks of maternal and fetal complications with mechanical
      heart valves treated with LMWH during pregnancy. We performed a review of the
      current medical literature through MEDLINE and EMBASE (1989 to 2004). Additional
      data sources included abstract proceedings, and reference lists of selected
      articles. Among 81 pregnancies in 75 women, the proportion of valve thrombosis
      was 8.64% (7/81; 95% CI, 2.52%-14.76%). The frequency of overall thromboembolic
      complication (TEC) was 12.35% (10/81; 95% CI, 5.19%-19.51%). Nine of ten patients
      with TEC received a fixed dose of LMWH and two of these received a fixed low dose
      of LMWH. Among 51 pregnancies whose anti-factor Xa levels were monitored, only
      one patient was reported to have a thromboembolic complication. The frequency of
      live births with LMWH was 87.65% (95%CI, 80.49%-94.81%). In pregnant women with
      mechanical heart valves, LMWH appears to be a suitable option to a vitamin K
      antagonist. The use of LMWH warrants monitoring and appropriate dose adjustments
      to maintain a 4-6 hr post-injection anti-factor Xa level at a minimum of 1.0 U/ml
      to decrease the incidence of TEC.

PMID- 15467906
TI  - Seminal clotting and fibrinolytic balance: a possible physiological role in the
      male reproductive system.
AB  - Semen contains enzymes and inhibitors of the haemostatic system as well as the
      high molecular weight seminal vesicle (HMW-SV) proteins. The former may have
      roles in seminal clotting and in liquefaction through "fibrinolytic" activity,
      which may ultimately affect fertility. Although a limited number of studies have
      addressed the subject, the role of clotting and fibrinolytic factors in semen
      remains poorly understood. The liquefaction time and the distribution of
      components vary across split ejaculates. This may have an important bearing on
      the way clotting/fibrinolytic factors in semen are assessed. Semen contains
      tissue factor (TF, Thromboplastin, CD142), which originates from the prostate and
      is associated with prostasomes. The function of TF (and prostasomes) in semen is
      still a matter for speculation. Recently the presence of minute amounts of factor
      VII in semen has been demonstrated but its importance is uncertain. Semen also
      contains a thrombin-like enzyme, prothrombin fragments 1 and 2 (F1+2), D-dimer
      (DD) and thrombin-antithrombin (TAT) complexes. The presence of several
      fibrinolytic factors has been demonstrated in semen but few questions about their
      potential impact on semen quality have been raised. Factors found include tissue
      plasminogen activator (t-PA), urinary plasminogen activator (u-PA) and plasmin.
      There are also traces of fibrinogen, plasminogen, plasminogen activator inhibitor
      1 (PAI-1), factor VIII coagulant activity (VIII:c) and fibrin monomers. The co
      ordinate expression of both TF and PAI-1 by decidual cells of the endometrium is
      believed to be important in maintaining haemostasis during endovascular
      trophoblast invasion. Kallikrein-like serine protease inhibitors including
      prostate specific antigen (PSA) are known to be present in semen at high
      concentrations. In semen PSA is also found in a complex form with protein C
      inhibitor (PCI) with mutually inhibitory consequences. A better understanding of
      the spectrum of coagulating and liquefaction agents in semen to include classical
      haemostatic processes and the pathogenesis resulting from any imbalances between
      or within either system may provide the basis for the development of more
      selective and efficient agents affecting global fertility. Here we review aspects
      of male reproductive physiology in the light of recent findings concerning
      conventional clotting/fibrinolytic systems in human semen with a view to
      stimulating further research.

PMID- 15467907
TI  - Expression of transcription factor Oct-4 and other embryonic genes in CD133
      positive cells from human umbilical cord blood.
AB  - A significant number of hematopoietic stem/progenitor cells (HSPC) in human
      umbilical cord blood could serve as a reservoir for the placental vasculature,
      yet, their morphological and functional features are not completely understood.
      Here, we describe the characterization of purified CD133(+) progenitor cells from
      umbilical cord blood, a subset of CD34(+) hematopoietic progenitors that were
      grown in proliferation medium containing Flt3-ligand, thrombopoietin and stem
      cell factor. Following isolation and enrichment of the CD133(+) cells by
      immunomagnetic cell sorting, they remained non-adherent for up to 40 days in
      culture and expressed different pluripotency markers including Sox-1, Sox-2, FGF
      4, Rex-1 and Oct-4.Oct-4 expression was confirmed by laser-assisted single cell
      picking with subsequent quantitative real-time RT-PCR. The expression of Oct-4
      indicates a pluripotent phenotype of CD133(+) cells and appears to be of
      functional relevance: After three weeks in endothelial differentiation medium,
      suspended cells became adherent, developed an endothelial cell-like morphology,
      bound fluoresceine isothiocyanate-labeled Ulex europaeus agglutinin-1, took up
      acetylated Di-LDL, and expressed other endothelial markers such as PECAM-1 or
      VEGFR-2. Concomitantly, Oct-4 expression was significantly reduced. Moreover,
      following treatment with retinoic acid, CD133(+) cells exhibited neural
      morphology associated with the expression of beta-III-tubulin. CD133(+) cells
      were found to express the luteinizing hormone/human chorionic gonadotropin
      (LH/hCG) receptor, detected by RT-PCR and immunocytochemistry. The recombinant
      human chorionic gonadotropin induced proliferation of the CD133(+) cells in a
      dose-specific manner. Our results indicate that CD133(+) HSPC from umbilical cord
      blood may have a greater differentiation potential than previously recognized and
      give rise to proliferative endothelial cells participating in placental
      vasculogenesis.

PMID- 15467908
TI  - Tissue factor and tissue factor pathway inhibitor levels in trophoblast cells:
      implications for placental hemostasis.
AB  - The placenta is a highly vascularized organ with fetal and maternal blood supply.
      Syncytiotrophoblasts (STB), which line the placenta villous are possibly involved
      in local hemostatic mechanisms. The aim of this study was to evaluate the levels
      of tissue factor (TF) and its inhibitors, tissue factor pathway inhibitor (TFPI,
      TFPI-2), in STB model within hemostatic and inflammatory environments. Human
      primary STB cell cultures were characterized by vascular and hormonal markers. TF
      and TFPI mRNA expression, protein levels and activity were determined and
      compared to human umbilical vein endothelial cells (HUVEC). High levels of TF
      were demonstrated in STB cells compared to low levels in HUVEC. In contrast, STB
      expressed lower TFPI levels than HUVEC. LPS and TNFalpha increased the high
      constitutive TF in STB, whereas LPS and IL-1alpha further reduced TFPI levels.
      The procoagulant tendency of STB identified by us may reflect the physiological
      need for immediate inhibition of hemorrhage in the placental inter-villous spaces
      in basal and inflammatory conditions. This hemostatic balance may be critical for
      normal placental function and pregnancy outcome.

PMID- 15467909
TI  - Unselected women with elevated levels of factor VIII:C or homocysteine are not at
      increased risk for obstetric complications.
AB  - Acquired and hereditary thrombophilias are associated with obstetric
      complications such as (pre-)eclampsia, HELLP syndrome and fetal loss. Our
      objective was to assess the risk of obstetric complications in women with
      elevated levels of FVIII:C or hyperhomocysteinemia, as compared with their
      relatives who had normal FVIII:C or homocysteine levels. From a large family
      study of patients with venous thromboembolism or premature atherosclerosis and
      elevated levels of FVIII:C or hyperhomocysteinemia (propositi), the obstetric
      histories of female first degree relatives, who had been pregnant at least once,
      were studied. Levels of FVIII:C and homocysteine (both fasting and post
      methionine loading) were determined. The number of obstetric complications was
      calculated and compared in women with normal and elevated levels of FVIII:C, and
      normal and elevated levels of homocysteine. Women with elevated levels of FVIII:C
      had a 15.4% risk for toxicosis, preeclampsia, or HELLP syndrome and a 23.9% for
      fetal loss. This was not statistically different from women with normal levels of
      FVIII:C. Women with hyperhomocysteinemia tended to have a lower risk for
      toxicosis, pre-eclampsia, or HELLP syndrome (8.0%, RR 0.6, 95% CI 0.2-1.7) and
      fetal loss (22.0%, RR 0.8, 95% CI 0.5-1.5) as compared to relatives with normal
      levels, although these differences did not reach statistical significance. If the
      analysis was limited to comparing extremes, the results did not materially
      differ. Unselected women with elevated plasma levels of FVIII:C or
      hyperhomocysteinemia are not at increased risk for obstetric complications as
      compared to their relatives with normal levels.

PMID- 15467910
TI  - Low molecular weight heparin (tinzaparin) therapy for moderate risk
      thromboprophylaxis during pregnancy. A pharmacokinetic study.
AB  - Low molecular weight heparin (LMWH) is used increasingly for prophylaxis and
      treatment of venous thromboembolism during pregnancy. However, the prophylactic
      dose for patients at moderate risk varies between centers, and the recommended
      LMWH dose for the non pregnant patient is frequently used in pregnant women. The
      aim of this study was to investigate the effects of pregnancy on the
      pharmacokinetics of anti-Xa levels during moderate risk thromboprophylaxis with
      the LMWH, tinzaparin. In 24 pregnant women, one of three doses of tinzaparin (50,
      75 or 100 IU/kg) were given according to the treating physician's assessment of
      their risk profile. Four-hour peak anti-Xa levels were measured throughout
      pregnancy and 24-hour profiles were measured at 28 and 36 weeks gestation. Doses
      were adjusted when peak anti-Xa levels fell below 0.1 IU/ml and, in some cases,
      when levels at 10 and 18 hours post injection were undetectable (<0.05 IU/ml).
      Our results showed that women receiving tinzaparin (50 IU/kg) frequently had peak
      (4 hour) anti-Xa levels below 0.1IU/ml and that 46% of these patients required
      dose adjustment. Similarly anti-Xa levels were also found to be low over the 24
      hour period. A starting dose of 75 IU/kg, once daily, gave greater anti-Xa cover
      over the 24-hour period and may avoid the need for dose adjustment. The results
      suggest that the pharmacokinetics of tinzaparin are affected by pregnancy. Larger
      studies are required to determine whether an increased tinzaparin dose (75 IU/kg)
      would be more effective in the prevention of thrombosis during pregnancy than 50
      IU/kg.

PMID- 15467911
TI  - Paracetamol (acetaminophen) warfarin interaction: NAPQI, the toxic metabolite of
      paracetamol, is an inhibitor of enzymes in the vitamin K cycle.
AB  - Paracetamol (acetaminophen) is generally considered to be the analgesic of choice
      for patients undergoing oral anticoagulant therapy. Occasionally, however,
      interactions have been reported with therapeutic doses of the analgesic, e.g. if
      the drug is taken for a longer period of time. The mechanism of this interaction
      is not clearly understood. We investigated the effects of paracetamol and its
      toxic metabolite N-acetyl-para-benzoquinoneimine (NAPQI) on in vitro vitamin K
      dependent gamma-carboxylase (VKD-carb) and vitamin K epoxide reductase (VKOR)
      activities. Paracetamol had no effect in either enzymatic reactions. NAPQI, on
      the other hand, appeared to interfere with VKD carb activity via two mechanisms;
      1) oxidation of the cofactor vitamin K-hydroquinone, 2) inactivation of the
      enzyme. The inactivation, in micromolar ranges, is not reversible and may be the
      result of covalent binding of NAPQI with functional amino acids. NAPQI also
      inhibited VKOR, but at higher concentrations. Unexpectedly, N-acetylcysteine was
      found to inhibit VKOR activity at concentrations that are obtained during rescue
      therapy of paracetamol intoxication. We conclude that, the potentiation of the
      oral anticoagulant effect by paracetamol is likely to result from NAPQI-induced
      inhibition of enzymes of the vitamin K cycle, particularly VKD-carb.

PMID- 15467912
TI  - Differential effects of heparin and low molecular weight heparin on
      osteoblastogenesis and adipogenesis in vitro.
AB  - We have previously demonstrated that heparin produces cancellous bone loss in
      rats due in part to a decrease in the number of osteoblasts lining the trabecular
      bone surface. In the present study, we use a stromal-derived cell culture system
      together with measurements of alkaline phosphatase (ALP) activity, to compare the
      effects of heparin and the low molecular weight heparin (LMWH), Fragmin, on
      osteoblast differentiation in vitro. In addition, we examined the possibility
      that both heparin and LMWH can induce adipogenesis in our stromal cell culture
      system. Both heparin and LMWH were found to produce a statistically significant
      (P < 0.01) and concentration-dependent decrease in the number of osteoblasts
      while increasing the number of adipocytes. When the effects of gravimetrically
      equivalent amounts of heparin and LMWH were compared, heparin had a 4-fold
      greater effect than LMWH. In contrast to heparin, N-desulfated heparin was found
      to have minimal effects on both osteoblast and adipocyte differentiation
      indicating that the heparin effect is not only chain-length dependent but also
      charge-dependent. The observation that LMWH has less of an effect on bone
      formation than heparin is compatible with the results of clinical trials
      indicating that LMWH produces less bone loss after long-term administration.

PMID- 15467913
TI  - Tissue factor pathway inhibitor-2 (TFPI-2) recognizes the complement and
      kininogen binding protein gC1qR/p33 (gC1qR): implications for vascular
      inflammation.
AB  - Evidence is accumulating to suggest that TFPI-2 is involved in regulating
      pericellular proteases implicated in a variety of physiologic and pathologic
      processes including cancer cell invasion, vascular inflammation, and
      atherosclerosis. Recent immunohistochemical studies of advanced atherosclerotic
      lesions, demonstrated a similar tissue distribution for TFPI-2, High Molecular
      Weight Kininogen (HK), and gC1qR/p33 (gC1qR), a ubiquitously expressed,
      multicompartmental cellular protein involved in modulating complement,
      coagulation, and kinin cascades. Further studies to evaluate TFPI-2 interactions
      with gC1qR demonstrated direct interactions between gC1qR and TFPI-2 using
      immunoprecipitation and solid phase binding studies. Specific and saturable
      binding between TFPI-2 and gC1qR (estimated Kd: approximately 70 nM) was observed
      by ELISA and surface plasmon resonance (Biacore) binding assays. Binding was
      inhibited by antibodies to gC1qR, and was strongly dependent on the Kunitz-2
      domain of TFPI-2, as deletion of this domain reduced gC1qR-TFPI-2 interactions by
      approximately 75%. Deletion of gC1qR amino acids 74-95, involved in C1q binding,
      had no effect on gC1qR binding to TFPI-2, although antibodies to this region and
      purified C1q both inhibited binding, most likely via allosteric effects. In
      contrast, HK did not affect TFPI-2 binding to gC1qR. Binding of TFPI-2 to gC1qR
      produced statistically significant but modest reductions in TFPI-2 inhibition of
      plasmin, but had no effect on kallikrein inhibition in fluid phase chromogenic
      assays. Taken together, these data suggest that gC1qR may participate in tissue
      remodeling and inflammation by localizing TFPI-2 to the pericellular environment
      to modulate local protease activity and regulate HK activation.

PMID- 15467914
TI  - Delayed immunologic thrombocytopenia induced by abciximab.
AB  - Abciximab is an anti-GPIIb-IIIa drug widely used to prevent thrombotic
      complications during percutaneous coronary intervention. We now report on the
      immunologic origin of thrombocytopenia developing between 7 and 12 days after the
      onset of abciximab infusion. Antibodies directed against abciximabcoated
      platelets were located in 5 patients with delayed thrombocytopenia, just as they
      were present in a patient whose platelet count fell within a few hours after
      receiving the drug. Abciximab-dependent IgG antibody was revealed in serum using
      control platelets in the monoclonal antibody immobilization of platelet antigens
      assay (MAIPA) performed with SZ22, a MoAb to GPIIb. The presence of IgG
      antibodies specific for platelets sensitized with abciximab was confirmed by flow
      cytometry. They were not located in 13 patients receiving abciximab but whose
      platelet counts remained stable. For three patients, antibodies were transient
      and their presence related to the extent of the thrombocytopenia. Surprisingly,
      antibodycontaining plasma from three patients induced abciximabdependent
      activation and aggregation of normal platelets, a finding confirmed by electron
      microscopy. Immunogold labeling revealed that abciximab was associated with
      platelets in the aggregate, suggesting that its inhibitory effect was overcome by
      the platelet stimulation. In summary, these results show that abciximab-dependent
      thrombocytopenia can be delayed and potentially prothrombotic.

PMID- 15467915
TI  - Platelets from Munc18c heterozygous mice exhibit normal stimulus-induced release.
AB  - A critical aspect of hemostasis is the release of clot-forming components from
      the three intra-platelet stores: dense core granules, alpha-granules and
      lysosomes. Exocytosis from these granules is mediated by soluble (SNAPs and NSF)
      and integralmembrane proteins (v- and t-SNAREs). Three SM (Sec1/Munc18) proteins
      are present in mouse platelets (Munc18a, 18b and 18c) and each potentially
      regulates exocytosis via modulation of their cognate syntaxin binding partner. To
      define the molecular machinery required for platelet exocytosis, we analyzed
      platelets from Munc18c heterozygous knockout mice. These platelets show a
      decrease in Munc18c but no apparent reduction in other secretory machinery
      components. No differences in the rates of aggregation or of secretion of [(3)H]
      5HT (dense core granules), platelet factor 4 (alpha-granules), or hexosaminidase
      (lysosomes) were detected between platelets from Munc18c heterozygous knockout or
      wild-type mice. The platelets also show normal morphology. Contrary to a
      predicted requirement for Munc18c in platelet secretion, data reported here show
      that reducing Munc18c levels does not substantially alter platelet function.
      These data show that despite Munc18c's role in platelet secretion, the lack of a
      secretion defect may be attributed to compensation by other Munc18 isoforms or
      that one allele is sufficient to maintain secretion under standard conditions.

PMID- 15467916
TI  - Contamination of coagulation factor concentrates with human parvovirus B19
      genotype 1 and 2.
AB  - Human parvovirus B19 (B19) DNA has frequently been detected in plasma-derived
      coagulation factor concentrates. Furthermore, transmission of B19 infection was
      observed, indicating presence of the infectious virus despite routine viral
      inactivation/removal procedures during the manufacturing process. Recently, human
      parvovirus DNA isolates, variant from B19, have been identified resulting in
      classification of B19 virus into three distinct genotypes, with all viruses
      previously classified as B19 belonging to genotype 1. So far, there is no
      information available on contamination of clotting factor concentrates with
      genotype 2. Therefore, we analysed 202 different factor concentrate lots for
      genotype 1 and 2 DNA by PCR. Analysis of one hundred eighty-one lots representing
      13 different products, administered over the last three years, was compared to 21
      lots (8 products) used until the early 1980s which had not been treated by viral
      inactivation procedures. Genotype 1 DNA was detected in 77/181 (42.5%) currently
      administered lots, and 17/21 (81%) previously used lots. The level of genotype 1
      DNA contamination was similar in currently and previously administered
      concentrates. Genotype 2 DNA was found in 5/202 (2.5%) lots, all of which were co
      contaminated with genotype 1 DNA. DNA sequence analysis showed that the PCR
      double positive concentrates contained typical genotype 1 and genotype 2 DNA.
      Because genotype 2 appears to cause a similar spectrum of diseases as genotype 1,
      simultaneous detection of genotype 2 by nucleic acid amplification testing (NAT),
      now widely applied to plasma pools for genotype 1, would give an added level of
      safety to blood products.

PMID- 15467917
TI  - On the mode of action of thrombin-induced angiogenesis: thrombin peptide, TP508,
      mediates effects in endothelial cells via alphavbeta3 integrin.
AB  - In a previous report we have presented evidence that thrombin interacts with
      alpha(v)beta(3) integrin in endothelial cells at the molecular and cellular
      level. This interaction was shown to be of functional significance in vitro and
      in vivo and contributed to activation of angiogenesis by thrombin. In the present
      study, we have used a synthetic thrombin peptide, TP508, which represents
      residues 183 to 200 of human thrombin. This peptide lacks the catalytic site of
      thrombin but contains the thrombin RGD sequence. Immobilized (surface-coated)
      TP508 peptide, like thrombin, supported alpha(v)beta(3) integrin-dependent
      endothelial cell attachment and haptotactic migration. These effects were
      specific (a scrambled TP508 peptide was without effect), and dosedependent. The
      RGD sequence was essential since a modified TP508 peptide, which contained RAD
      sequence instead of RGD, was inactive. Immobilized TP508 peptide stimulated
      phosphorylation of mitogen-activated protein kinases and focal adhesion kinase,
      the signal transduction pathways characteristic for integrin activation. On the
      other hand, TP508 peptide, when in solution, did not mimic other thrombin
      promoted angiogenic effects, such as that of activation gelatinase A,
      upregulation of expression of vascular endothelial growth factor receptor mRNA or
      prostacyclin PGI(2) release in endothelial cells. On the contrary, soluble TP508
      acted as an antagonist for the aforementioned effects of thrombin. TP508 peptide
      inhibited these thrombin-induced effects through a RGD and alpha(v)beta(3)
      related mechanism. The antagonism with thrombin or thrombin receptor activating
      peptide was specific and involved at least in part mitogen-activated protein
      kinases activation. These results point to the importance of RGD sequence of
      thrombin in mediating effects on endothelial cells and angiogenesis.

PMID- 15467918
TI  - Fibrinogen regulates the expression of inflammatory chemokines through NF-kappaB
      activation of endothelial cells.
AB  - The objective of this study was to characterize the role of fibrinogen in
      stimulating expression of inflammatory chemokines in endothelial cells through NF
      kappaB activation. Human umbilical vein endothelial cells (HUVEC) were exposed to
      fibrinogen up to 3,000 microg/ml, and NF-kappaB activation was assessed using
      electrophoretic mobility shift assay (EMSA). Fibrinogen exposure resulted in a
      concentration dependent increase in NF-kappaB activation that reached a maximum
      at 1,000 microg/ml after 4 hours and was sustained up to 24 hours. The effect was
      inhibited by antibodies to alpha(v)beta(3) and alpha(5)beta(1) and by the GRGDS
      peptide, indicating integrin involvement. Preincubation with Mn(2+) lowered the
      fibrinogen concentration-dependence, consistent with integrin activation.
      Supershift assays demonstrated involvement of the p50, p65 and c-Rel components
      of NF-kappaB. Fibrinogen exposure also resulted in up-regulation of expression of
      monocyte chemoattractant protein-1 (MCP-1) and of interleukin-8 as shown by RNase
      protection assays and by real-time RT-PCR. Increased secretion of MCP-1 was
      confirmed by ELISA. Parthenolide, an IkappaB kinase inhibitor, prevented up
      regulation of MCP-1 by fibrinogen, linking this response to NF-kappaB activation.
      From our findings, we conclude that fibrinogen regulates NF-kappaB activation and
      expression of inflammatory chemokines in endothelial cells and may be involved in
      mediating inflammatory processes.

PMID- 15467919
TI  - Haplotype analysis of the matrix metalloproteinase 3 gene and myocardial
      infarction in a Chinese Han population. The Beijing atherosclerosis study.
AB  - Matrix metalloproteinase (MMP) 3 plays an important role in the pathogenesis of
      myocardial infarction (MI). Up to now, there has been conflicting data regarding
      the possible contribution of the MMP3 -1612 5A/6A promoter polymorphism to MI. In
      this study, we have investigated the possible association of three polymorphisms
      (-1612 5A/6A, -376C/G, Glu45Lys) in the MMP3 gene with MI in a Chinese Han
      population. The polymorphisms were analyzed in 509 patients with MI, and in 518
      healthy controls. The frequency of the 5A allele was 14% in the healthy controls,
      which is less than in Western populations (40%-52%). Logistic regression analyses
      of individual polymorphisms indicated that individuals carrying the -1612 5A
      allele had an increased risk of MI (odds ratio [OR] 1.75, 95% confidence interval
      [CI] 1.28 to 2.40), as did those carrying the -376 G allele (OR 1.78, 95% CI 1.33
      to 2.38). The three polymorphisms studied were found to be in strong linkage
      disequilibria. Haplotype analyses showed that the 5A-G-Lys haplotype (-1612 5A, 
      376G and 45Lys) was independently associated with susceptibility to MI. Taken
      together, the effect of the MMP3 polymorphisms studied may be attributable to the
      -1612 5A/6A polymorphism. We conclude that the MMP3 -1612 5A/6A polymorphism is
      associated with MI in our population, implying that individuals of the 5A allele
      carriers have an increased risk of suffering MI.

PMID- 15467921
TI  - Platelet-monocyte interaction and GPIIb/IIIa blockade.

PMID- 15467920
TI  - Blood coagulation kinetics: high throughput method for real-time reaction
      monitoring.
AB  - A high throughput 384-well plate assay of blood function in 60 microl reactions
      with the fluorogenic thrombin substrate, boc-VPR-MCA, allowed for real-time
      monitoring of coagulation under a diverse set of reaction conditions. Using
      recalcified, citrated whole blood diluted 3-fold with corn trypsin inhibitor (to
      block Factor XIIa), addition of 0 to 13.8 pM of tissue factor (TF) reduced the
      time of maximal rate of thrombin production T(max) from 45 min to 11 min. Over
      this range of TF,T(max) was reduced from 35 min to 6 min by co-addition of 10 nM
      convulxin to activate platelets via GPVI. The maximal rate of thrombin production
      at T(max) was not a function of exogenously-added TF,Va, or reVIIa, but increased
      30% with added convulxin. Addition of 0.07 to 0.7 pM TF along with convulxin
      produced small, but detectable reductions in T(max). Addition of up to 0.67 nM
      reVIIa reduced T(max) by up to 53% in the range of 0.7 to 7 pM TF. Interestingly,
      platelet factor 4 (2.7 microM) caused a prolongation of T(max) from 45 min to 78
      min at 0 TF, while protamine (1.8 microM) reduced T(max) to 30 min at 0 TF.
      Finally, combinatorial reaction studies with exogenously-added ADP, histamine,
      fMLP, indomethacin, anti-CD18, and fibrinogen revealed no unusual synergies
      amongst the agents, but demonstrated a striking procoagulant activity of added
      fibrinogen, due to protease contaminants in the "purified" fibrinogen. This high
      throughput approach allowed automated profiling of blood (50 reactions/ml of
      blood) to generate large data sets for testing cellular-proteomic kinetic models,
      screening drug interactions, and potentially monitoring subtle changes in the
      functional phenotype of a patient blood sample.

PMID- 15467922
TI  - Activated protein C enhances tPA-catalyzed Glu-plasminogen activation in the
      presence of poly-D-lysine.

PMID- 15467923
TI  - Rebuttal: factor XII levels, factor XII 46 C>T polymorphism and venous
      thrombosis: a word of caution is needed.

PMID- 15467925
TI  - [OCT in macular holes].
AB  - The traditional Gass classification of macular holes can now be supplemented by
      additional and more detailed morphologic information obtained with optical
      coherence tomography (OCT). The perifoveal vitreous detachment and subsequent
      anterior foveal traction is considered to be the primary pathomechanism of
      macular hole formation. In cases of persistent traction on the fovea it may lead
      to foveal dehiscence. A possible explanation for intraretinal cyst formation may
      be secondary vitreous body fluid accumulation within the retina. A classification
      of macular holes based on additional information from OCT images is possible.
      Thus, OCT is a valuable tool for differential diagnosis of a pseudo macular hole
      versus macular hole, precise stage classification, therapy decision making
      process, outcome control after macular surgery, and prognosis prediction.

PMID- 15467926
TI  - [Telematic-assisted self-tonometry (TAS)].
AB  - BACKGROUND: Close supervision of intraocular pressure (IOP) means monitoring an
      important risk factor for glaucoma. METHOD: After instruction in its use,
      patients measure their own IOP several times a day with the Drager self
      tonometer. The measurements are subsequently transmitted to a server via the
      telephone keypad and recorded separately for each patient. The software enables
      statistical evaluation of the pressure levels collected. RESULTS: Up to now 30 of
      35 patients transmit measurements or had done so for at least 6 months.
      Registration of measurement levels covering months and years provides the
      opportunity for optimizing treatment and hence can be considered a start toward
      quality assurance in the treatment of glaucoma patients. CONCLUSION: TAS is a
      cost-efficient method for obtaining long-term profiles of eye pressure. Thus, the
      possibility exists for early therapeutic intervention in patients at risk. The
      compliance gained by the close relationship between the physician and the patient
      represents a positive prognostic factor.

PMID- 15467927
TI  - [Results of wavefront-guided LASIK].
AB  - BACKGROUND: Wavefront-guided LASIK procedures provide patients with customized
      corneal treatments. The computer ablation profiles correct both spherical and/or
      cylindrical errors of refraction and aberrations up to the fifth order. METHODS:
      We performed wavefront-guided LASIK treatments on 62 patients using the Keracor
      217 Z. The spherical equivalent was -6.11 +/-2.29 D on the average. Data
      collected for 3 months were evaluated to determine the predictability, efficacy,
      stability, and safety of the refractive procedure. RESULTS: We found good
      predictability of the refractive result after correcting -1 to -6 D of myopia.
      Beyond -7 D there were over- and undercorrections of +/-2 D in 10% of the
      procedures. A UCVA of 0.8 or better was observed in 53% of the patients 3 months
      postoperatively, and 75% of the patients reached a BCVA of 0.8 or better. After 3
      months 6% lost 2 lines, 22% lost 1 line, 22% of the patients gained 1-2 lines,
      and BCVA remained unchanged in 55%. The fluctuation of the refraction was about 
      0.23 D during the first 3 postoperative months. CONCLUSIONS: The low and middle
      range of myopia can be corrected very accurately using the wavefront technology.
      Higher degrees of myopia face both under- and overcorrections. Postoperative
      refractions become stable very quickly. However, the visual acuity changes even 6
      months postoperatively. From our point of view, wavefront correction by LASIK
      should be more reliable in terms of centration, accuracy, and standardization to
      get better results.

PMID- 15467928
TI  - [SILK--Steroid-induced lamellar keratopathy. A case report].
AB  - CASE REPORT: After uneventful myopic LASIK, both interfaces of a 31-year-old,
      healthy male patient showed 5 days (right eye) and 7 days (left eye)
      postoperatively a diffuse, multifocal infiltration confined to the flap interface
      which was interpreted as a diffuse lamellar keratitis, stage 2-3. The routine
      postoperative treatment with local antibiotics and steroids was intensified to
      local steroids hourly. At that time intraocular pressure (IOP) was 19 mmHg
      (right) and 18 mmHg (left) (centrally measured by Goldmann applanation
      tonometry). Following 2 weeks under this therapy the keratitis did not resolve
      and IOP increased up to 30 mmHg. Local and systemic antiglaucomatosa were
      administered and IOP was reduced to 22 and 24 mmHg, respectively. Corneal
      interface infiltration, however, remained unchanged. Only the complete stop of
      the local corticosteroids induced a rapid regression and corneal transparency
      returned. IOP was normalized down to 10 mmHg without additional therapy.
      DISCUSSION: 1) It is essential to measure IOP in the early postoperative phase
      after LASIK, especially in cases of corneal haze. 2) After corneal refractive
      surgery with high corneal ablation, IOP data in the upper range has to be
      interpreted as pathological. 3) Steroid-induced lamellar keratopathy is
      postulated as being a separate entity. 4) In cases of stromal infiltration after
      LASIK and increased IOP, local steroids have to be reduced immediately.

PMID- 15467930
TI  - Residency should be expanded to 4 years.

PMID- 15467929
TI  - [Local anesthesia in ophthalmic surgery].
AB  - In recent years anesthesia modalities have changed in ophthalmic surgery. A
      growing trend toward the use of topical anesthesia in cataract surgery is
      apparent. The present-day techniques used in ophthalmic surgery are retrobulbar
      anesthesia, peribulbar anesthesia, subtenon anesthesia, and subconjunctival
      anesthesia as injection techniques, topical anesthesia using drops, gel, or
      sponge, and intracameral anesthesia. Injectable anesthesia (RBA, PBA, STA)
      provides a higher level of analgesia and globe akinesia. With injection
      techniques the risks of vis a tergo and anesthetic complications increase; the
      level of analgesia after topical anesthesia could be improved by supplementation
      with i.v. narcotics.

PMID- 15467931
TI  - Have FPs failed to ask some important questions?

PMID- 15467932
TI  - Authors respond to "cultural issues skill development" letter.

PMID- 15467933
TI  - Teaching medicine using interactive games: development of the "stumpers" quiz
      show game.

PMID- 15467934
TI  - Sprint or marathon? Strategic planning for the society.

PMID- 15467935
TI  - Using "pearls" to ensure that learners learn key information.

PMID- 15467936
TI  - A Web-based approach to teaching students about diagnostic reasoning.
AB  - BACKGROUND: Web-based curricula can decrease classroom time and provide self
      paced, active learning experiences for medical students. INTERVENTION: In our
      family medicine clerkship, we implemented a Web-based module on applying
      diagnostic reasoning to determine the likelihood that a patient has Group A beta
      hemolytic streptococcal pharyngitis based on the history, physical examination,
      and diagnostic tests. RESULTS: Students rated the module more favorably than
      other classroom sessions and homework assignments. Most students accurately
      calculated pretest and posttest probabilities in a write-up of an actual patient
      with a sore throat. CONCLUSIONS: This Web-based module was well received and
      effective.

PMID- 15467937
TI  - Building closeness, understanding, and tolerance among residents: the family
      genogram.

PMID- 15467939
TI  - Doc-U-drama: using drama to teach about patient safety.

PMID- 15467940
TI  - Drawing on the legacy of general practice to build the future of family medicine.

PMID- 15467941
TI  - Undiagnosed obesity: implications for undiagnosed hypertension, diabetes, and
      hypercholesterolemia.
AB  - BACKGROUND AND OBJECTIVES: Since obesity is a risk factor for hypertension,
      diabetes, and hypercholesterolemia, health care providers should screen obese
      individuals for these common diseases. It is possible that obese adults are not
      receiving appropriate screening for these diseases. This study's objective was to
      describe the prevalence of undiagnosed obesity, diabetes, hypertension, and
      hypercholesterolemia, in a nationally representative sample of obese US adults,
      by patients' recollection of whether they had received such a diagnosis. METHODS:
      The prevalence of undiagnosed disease was obtained by identifying respondents in
      the 1999-2000 National Health and Nutrition Examination Survey (NHANES) who had
      findings consistent with a condition but who did not report being told they had
      that condition by a health care provider. RESULTS: The prevalence of undiagnosed
      obesity, diabetes, hypertension, and hypercholesterolemia in currently obese US
      adults is 22.9%, 11.3%, 16.1%, and 37.7%, respectively. Significant predictors of
      undiagnosed obesity include black race and younger age. In addition, obese adults
      with excellent self-reported general health condition and lower body mass index
      are less likely to have diagnosed obesity. CONCLUSIONS: Health care providers are
      missing valuable opportunities to address obesity and diagnose diabetes,
      hypercholesterolemia, and hypertension in obese adults. An emphasis on screening
      obese individuals for these diseases is needed to improve health promotion.

PMID- 15467942
TI  - Doctors on-line: using diffusion of innovations theory to understand internet
      use.
AB  - BACKGROUND AND OBJECTIVES: Family physicians must be aware of the latest and best
      evidence for a broad range of clinical and public health topics. The Internet is
      an important source of this information, but not all family physicians use the
      Internet. This study used "diffusion of innovations" theory to identify
      strategies for increasing Internet use by family physicians. METHODS: We
      conducted a mail survey of 58 family physicians in a midsized Northeastern
      metropolitan area in the United States to assess Internet use and identify
      sources from which physicians obtain medical information. We then used diffusion
      of innovations theory to describe the process by which physicians learn and
      develop skills at using the Internet. RESULTS: Internet use begins when
      physicians are not constrained by a heavy patient volume and are able to learn
      about and observe the benefits of Internet use. When they experience its
      usefulness, their Internet browsing and searching develop and become more
      effortless and less time-consuming. CONCLUSIONS: The innovation attributes of
      diffusion of innovations theory act as predictors of Internet use among family
      physicians. Internet use by family physicians might be increased by providing
      them time to learn about how to use it and to experience its benefits.
      Integration of continuing medical education courses created for the purpose of
      developing and enhancing Internet usage skills into their schedule may be a
      workable solution. Demographic factors such as gender and training recency have
      no influence on Internet use by family physicians.

PMID- 15467943
TI  - Developing a Web site in primary care.
AB  - BACKGROUND AND OBJECTIVES: While content, navigability, and usability are
      essential qualities of effective Web sites, the health care literature contains
      limited discussion of these issues. This article describes how knowledge gained
      through focus groups, Web site searches, and individual interviews were used to
      develop and improve a health-related Web site. METHODS: We conducted 10 focus
      groups and searches of existing Web sites in preparation for developing a Web
      site about colorectal cancer (CRC) screening. We conducted 30 in-depth interviews
      to assess content, navigation, and usability of a new CRC Web site, using
      participants recruited from Michigan communities with a low incidence of CRC
      testing. Targeted participants were 50-70 years of age, had no prior experience
      with CRC testing, and had variable comfort levels with Internet use. RESULTS:
      Existing CRC screening Web sites uniformly use user-directed navigation and have
      little variation in content. Our study participants stimulated revisions in
      content, navigation, and usability. Revised content factors included
      comprehension, utility, and appeal. Navigation changes focused on logical
      transition between sections. Usability changes included user focus and clarity of
      graphics/ text. CONCLUSIONS: We found focus groups, Web site searches, and
      individual interviews useful in developing and testing content, navigation, and
      usability of a CRC screening Web site. These steps provide methodological
      procedures for developing and revising health-related Web sites.

PMID- 15467944
TI  - Ranking departments of family medicine: the eye of the beholder?
AB  - BACKGROUND AND OBJECTIVES: During each of the past several years, a nationally
      circulated periodical (US News & World Report) has provided a ranking of medical
      schools and their respective specialty departments. In contrast to the method
      used to rank medical schools, medical specialties, including family medicine, are
      ranked based solely on ratings by deans and senior faculty at peer schools. This
      study's purpose was to explore how closely this expert opinion-based process
      matches actual objective and quantifiable data about departmental performance.
      METHODS: Available quantifiable data in the following categories were obtained:
      administration, academic productivity, and medical student and resident
      education. Based on their ranking in a category, each department was awarded one
      to five stars depending on the quintile they achieved (except for the dichotomous
      variable pertaining to the presence of a postresidency fellowship). Five stars
      indicate a ranking in the highest quintile. RESULTS: In regards to success in
      administration, research, and residency education and production of family
      physicians, the departments, on average, were rated 3.4, 4.2, and 3.6 stars,
      respectively. Overall, half of the departments consistently ranked in the top
      quartile, as indicated by an average score of 4.0 to 5.0 stars. CONCLUSIONS: Many
      of the departments rated highly in the US News & World Report rankings of the
      departments of family medicine rated very high in the areas of administration,
      research, and education as determined by quantifiable information. In contrast,
      several highly ranked departments were not rated favorably in areas usually
      associated with excellence in academics.

PMID- 15467945
TI  - Questioning the Future of Family Medicine.
AB  - The Future of Family Medicine Report is a milestone in the development of the
      discipline devoted to generalist physicians and the patients and communities they
      serve. From this vantage point, we must take stock of our past as well as our
      future. In this personal essay, I question the process of the Project and the
      conclusions of the Report. Important questions remain, and I list 10 that seem
      too important to leave unasked. Hope for the future springs from the capacity of
      the family physician to learn from experience, adapt to change, and care for
      people.

PMID- 15467947
TI  - Assessing departments of family medicine.

PMID- 15467946
TI  - Fixing family medicine residency training.
AB  - The number of US medical students entering family medicine continues to decline.
      Despite the increased presence of family physicians on medical school faculty and
      increased exposure to family medicine during training, students still cite lack
      of respect and excessive knowledge base to master as reasons for not choosing our
      specialty. Specific changes must be made to family medicine residency training to
      make it more attractive to students and more compatible with the realities of
      practice today. These changes include eliminating maternity care as a
      requirement, lengthening training to 4 years, and reducing the number of
      residency slots available. These changes will ensure that graduating family
      physicians will be better prepared for practice, better qualified to obtain
      privileges in the hospital and clinic, and more respected by their colleagues and
      the public.

PMID- 15467950
TI  - [Apropos continuing education].

PMID- 15467949
TI  - [Metastatic infiltration of the small bowel following a signet ring gastric
      carcinoma].

PMID- 15467951
TI  - [Extended infiltration of the colon by a metastasis from a signet ring
      carcinoma].

PMID- 15467960
TI  - [Mental health in an ageing society].

PMID- 15467961
TI  - [Vascular dementia -- diagnosis, prevention and treatment].
AB  - OBJECTIVE: In this article, current trends in diagnosis, prevention and therapy
      of vascular dementias (VaD) are summarized. METHODS: Based on the conceptual
      background and pathophysiology of VaD, current diagnostic approaches and results
      from recent large-scale randomised preventative and therapeutic studies are
      reviewed. RESULTS: Epidemiological cohort studies and first intervention trials
      with anti-hypertensive drugs demonstrated the usefulness of antihypertensive
      drugs in the prevention of dementia. For the treatment of manifest VaD, no
      pharmaceutical substance has been approved to date, despite positive results in
      controlled studies with acetylcholinesterase inhibitors. CONCLUSIONS: Long-term
      control of vascular risk factors before dementia has occurred appears to be the
      most important strategy to reduce the incidence of VaD.

PMID- 15467962
TI  - [Dementia disorders, behavior problems and the care of clients in geriatric day
      care compared to residents in homes for the elderly: a cross-sectional study in
      eight communities in Baden].
AB  - AIM: The study aims to compare clients using institutions of geriatric day-care
      to residents in homes for the elderly with regard to functional impairment,
      dementia disorders, behavior problems and the care situation. METHODS: A cross
      sectional study of 17 geriatric day-care facilities in eight towns and cities in
      Baden examined the data for all 257 clients who received care on a given
      reference date. These clients were compared to a reference population drawn from
      all residents (N = 1,387) of 15 randomly selected residential and nursing homes
      in the city of Mannheim, whereby identical assessment procedures were used by
      qualified nursing staff. RESULTS: The average age of subjects in both groups was
      around 80 years, over three-fourths of whom were women. Home residents were more
      limited than the clients of geriatric day-care facilities with regard to their
      activities of daily living, above all with regard to their mobility. The
      percentage of moderate to severe dementia disorders at 58.6 % was equally high in
      both groups. In addition, symptoms of depression and behavior problems were
      observed among a substantial number of the day-care clients. While the inpatient
      sector places greater emphasis on basic care and treatment, day-care institutions
      focus primarily on measures of social therapy. CONCLUSIONS: The high percentage
      of demented yet still mobile clients in day-care facilities indicates the
      particular importance of this target group when it comes to providing at least
      partial stress relief for family care-givers.

PMID- 15467963
TI  - [Non-cognitive symptoms of dementia -- prevalence and consequences].
AB  - OBJECTIVE: While the importance of non-cognitive symptoms of dementia is
      increasingly recognized there exist nearly no studies investigating the frequency
      of these symptoms among general hospital inpatients and nursing home residents.
      METHOD: The sample consisted of elderly persons admitted to medical hospital
      departments (N = 372) and nursing homes (N = 249) in Austria. Study participants
      were investigated by research psychiatrists using the Clinical Interview
      Schedule. RESULTS: Of all patients with dementia, in medical departments 28 % and
      in nursing homes 38 % had marked or severe non-cognitive symptoms. Using
      multivariate regression procedures non-cognitive symptoms turned out to be
      significant predictors for nursing home referral, for a prolonged duration of
      hospital stay, and for impaired self-care. CONCLUSIONS: Non-cognitive symptoms of
      dementia occur frequently and have several negative consequences. Since such non
      cognitive symptoms might be treatable, they should receive sufficient attention
      from the staff.

PMID- 15467964
TI  - [Optimised neuro-psychological tests on different stages of dementia
      diagnostics].
AB  - OBJECTIVE: We postulated three level of dementia diagnostics: the general
      practitioner, the neuro-psychiatrist and the memory clinic. For each level,
      definite diagnostic questions were defined as the main diagnostic focus. The aim
      was to establish a staged process in dementia diagnostics, proposing for each
      diagnostic level a specific test battery suitable for the respective diagnostic
      focus. On each level, the test battery can be supplemented by other tests
      proposed on the subsequent diagnostic level. METHOD: 159 patients were examined
      clinically, neuropsychologically, and neuroradiologically. Discriminant analyses
      were computed to find out which tests out of a comprehensive test battery are
      most suitable in differentiating between several diagnostic groups. RESULTS: The
      diagnostic accuracy of the test batteries proposed for general practitioners and
      neuro-psychiatrists were maximally 3 % below that of the complete test battery
      which we suggest for memory clinics. CONCLUSION: Depending on the diagnostic
      level, a definite short form of a comprehensive test battery can be implemented
      without unacceptably reducing diagnostic accuracy.

PMID- 15467965
TI  - [Incidence and risk factors of delirium after hip surgery].
AB  - OBJECTIVE: Postoperative delirium is common among elderly hip surgery patients.
      The objective of the current study was to determine the incidence of delirious
      states and to identify possible risk factors. METHOD: The sample consisted of 200
      consecutive patients, age 60 years and older, who underwent hip surgery because
      of acute hip fracture or elective hip replacement. Patients were prospectively
      assessed preoperatively and on a daily basis postoperatively using the Confusion
      Assessment Method (CAM). Associations between risk factors and delirium were
      analysed by means of multiple logistic regression models. RESULTS: 20.5 % of the
      sample were diagnosed with postoperative delirium. Statistically significant risk
      factors for the development of delirium were higher age, lower preoperative
      cognitive test performance and severe physical comorbidity. Some other putative
      risk factors tended to be associated with postoperative delirium, but failed to
      reach statistical significance. CONCLUSIONS: The study confirmed a high incidence
      of delirium among hip surgery patients. Apart from established risk factors like
      old age, low cognitive test performance, and comorbidity, no other significant
      risk factors could be identified.

PMID- 15467966
TI  - ["Understanding the mass destruction of nerve cells"].
AB  - OBJECTIVE: One important step towards an early diagnosis and treatment of
      dementia is the recognition and understanding of disease by the public. METHOD:
      Since laymen's opinion is influenced by mass media, the portrayal of cognitive
      disorders was analysed using four volumes of a regional newspaper ("Leipziger
      Volkszeitung", LVZ). RESULTS: The predominant topics were related to cause and
      symptoms of dementia. Memory loss was depicted as the main symptom, non-cognitive
      symptoms were completely neglected. Therapy options and prevention were scantily
      touched; if at all, the tenor was one of futility. Unfortunately, dementia was
      often used as a devaluating metaphor. CONCLUSIONS: In the media, scientifically
      sound information on dementia is rare. Supporting journalists with expert
      knowledge may help dementia sufferers to profit from the new developments in the
      field.

PMID- 15467967
TI  - [Research on public mental health in the German-speaking area].
AB  - OBJECTIVE: From the point of view of public mental health, research on mental
      disorders still leads a shadowy existence in the German-speaking countries. The
      aim of this work is to determine the state of affairs of research in this field
      based on the publications in scientific journals. METHOD: Including the German
      and international journals listed in the Science Citation Index (SCI) and the
      Social Science Citation Index (SSCI) for the psychosocial field, a systematic
      search was done for the year 2003. RESULTS: The majority of public mental health
      research in the German-speaking countries is focused on a few institutions only.
      Particularly for Germany, clear-cut regional distinctions can be found. While
      there is a large amount of mental health care research and attitudinal research,
      only a small amount of the research is focused on prevention and health
      economics. CONCLUSION: Our analysis indicates future avenues of research. There
      is legitimate hope that existing gaps will be overcome in the future.

PMID- 15467968
TI  - Chronobiotic protocol and circadian sleep propensity index: new tools for
      clinical routine and research on melatonin and sleep.
AB  - Twenty years ago, chronobiology was a major topic in medical research, especially
      in psychiatry. Over time, however, clinicians lost interest in the subject
      because studies had failed to lead to any practical benefits for patient
      diagnosis or therapy. Today, the field of chronobiology appears to be on the
      verge of a renaissance. Over the past decade, our understanding of the basic
      mechanisms of the circadian timing system (CTS) has increased so rapidly that
      experts in the field sometimes speak of a "clockwork explosion." It has become
      apparent that, in order to treat circadian rhythm disturbances, new diagnostic
      tools are needed so that researchers and physicians can make reliable
      measurements of CTS functionality (e.g., phase position and circadian rhythm
      amplitude). Although clinicians do have a phase marker for the CTS at their
      disposal, there are still no reliable markers for CTS output strength as measured
      by rhythm amplitude. The amplitude is considered to be the most important factor
      in CTS output because it determines the degree of temporal organization in human
      and animal physiology. In this paper, we would like to suggest that circadian
      sleep propensity (CSP) - the endogenously generated 24-hour variation in the
      drive to wakefulness and sleep - is the product of all circadian rhythms, serving
      the human brain at night by assisting it in the production of good-quality sleep.
      If this is indeed the case, developing a CSP index (CSPI) for use in routine
      polysomnography would be of great value. In addition, we will review current data
      on melatonin and its relationship to sleep, basing our analysis on the assumption
      that melatonin is a circadian hormone and a drug with highly time-dependent
      effects. Because of this special mode of action, future melatonin studies should
      employ a special chronobiotic protocol that precludes the use of crossover
      designs and requires outcome measures different from those used in studies on
      classical hypnotics.

PMID- 15467969
TI  - Impaired declarative memory in depressed patients is slow to recover: clinical
      experience.
AB  - INTRODUCTION: The temporal course of recovery of depressed patients' cognitive
      impairment is not fully understood. METHODS: We used the California Verbal
      Learning Test (CVLT) to test declarative memory in 24 depressed patients before
      and after 35 days of antidepressive treatment as well as after long-term follow
      up (> 12 months) in order to relate improvement of depression to recovery of
      cognitive impairment. RESULTS: Patients with complete remission after 35 days had
      generally been less impaired at baseline. The disturbance of declarative memory
      in treatment responders as well as in non-responders did not change from baseline
      to end of treatment (day 35). However, our results revealed normal values in the
      CVLT sum score as well as in measures of short- and long-delay free-recall
      measures in both groups after long-term full remission. DISCUSSION: We conclude
      that clinical response to antidepressive treatment precedes improvement of
      declarative memory. A low degree of impairment of declarative memory is
      associated with early complete remission of depression.

PMID- 15467970
TI  - Public attitudes towards psychotropic drugs: have there been any changes in
      recent years?
AB  - BACKGROUND: Two representative surveys conducted in the early 1990 s found very
      negative views on psychotropic medication among the German public. The question
      arises whether this reservation about drug treatment of mental disorders has
      persisted over the following decade, or whether there have been any changes.
      Furthermore, it will be examined whether the preexisting differences between East
      and West Germany can still be observed. METHODS: In 2001, a representative survey
      was conducted among the German population aged 18 years and older, using the same
      instrument for the assessment of perceived effects of psychotropic medication as
      in a previous survey in 1990. RESULTS: As expected, in 2001, those questioned
      were more ready to acknowledge beneficial effects of drug treatment. However,
      contrary to our expectation, the difference between East and West Germany has
      persisted, with people in the East still being more sceptical in their assessment
      of drug effects. CONCLUSION: Although public attitudes towards psychotropic drugs
      have improved somewhat over the last decade, the actual situation is far from
      being satisfying. Further efforts to improve public knowledge about the
      psychopharmacotherapy of mental disorders are needed.

PMID- 15467971
TI  - Subchronic effects of olanzapine on sleep EEG in schizophrenic patients with
      predominantly negative symptoms.
AB  - BACKGROUND: It is well known that sleep disturbance is an integral symptom of
      schizophrenia. In recent studies, a deficit of delta sleep has been observed in
      schizophrenic patients. Antipsychotic drugs with serotonin (5-HT2) receptor
      antagonistic properties are considered to have delta sleep promoting effects. We
      have investigated the effects of subchronic olanzapine treatment on sleep EEG in
      schizophrenic patients. METHODS: The effects of administration of olanzapine (15
      to 20 mg) on sleep were studied for four weeks in 10 male, drug-free patients
      suffering from schizophrenia with predominantly negative symptoms. Conventional
      sleep EEG parameters were investigated at baseline and after treatment with
      olanzapine for four weeks. Additionally, spectral power analysis of the EEG
      signal in distinct frequency bands was computed for different sleep stages.
      Psychopathology (PANSS, HAMD-17, HAMA) and side effects were assessed weekly.
      RESULTS: All patients improved, as measured by PANSS global scores. Compared to
      baseline, there was a significant improvement of parameters of sleep efficiency
      and an increase of delta sleep as well as REM sleep. Regarding spectral power
      values, no significant differences between baseline and treatment conditions were
      found. CONCLUSIONS: Sleep improvement was due to parameters of sleep efficiency
      and delta sleep, which may be related to serotonin antagonistic properties of
      olanzapine.

PMID- 15467972
TI  - Early administration of tiapride to young rats without long-lasting changes in
      the development of the dopaminergic system.
AB  - BACKGROUND: The benzamide tiapride, a selective dopamine D2/D3-receptor
      antagonist, can be used effectively in children to treat tic disorders and
      stuttering. Tiapride is a clinically safe substance (even during long-term
      treatment and when given to young children). Unfortunately, its probable effects
      on general brain development and the maturation of the dopaminergic system have
      not been investigated. Thus, important information for drug treatment in children
      is missing. Therefore, this study in rats describes tiapride's effects on several
      parameters of dopaminergic activity (dopamine transporter, D2 receptor, dopamine,
      DOPAC, and homovanillic acid in the striatum) seen after tiapride administration
      (30 mg/kg/day) to prepubertal (from day 25-39) and postpubertal (from day 50-64)
      rats. METHODS: Three groups of rats (n = 6) received tiapride within their
      drinking water for 14 days. Two groups were treated before puberty; one of those
      was killed at day 50, the other at day 90. The group treated after puberty was
      measured at day 90. A fourth group (n = 6) was treated from day 50 to day 53 and
      measured under tiapride at day 53. Changes were measured by ligand-binding assays
      (KD and Bmax values of dopamine transporter by [3H]-GBR binding and D2 receptor
      by [3H]- spiperone binding) and by HPLC (concentrations of dopamine, DOPAC, and
      homovanillic acid). RESULTS: The density of dopamine transporters and D2
      receptors remained unaffected after early (day 25) and late (day 50) tiapride
      administration. Only during the treatment period could a significant reduction of
      D2-receptor binding (displacement of spiperone) and of dopamine and DOPAC levels
      be stated. CONCLUSIONS: These data suggest that tiapride treatment during
      postnatal brain development causes no long-lasting changes in the development of
      the central dopaminergic system and is in line with clinical experience in
      children.

PMID- 15467973
TI  - Open trial of mirtazapine in patients with fibromyalgia.
AB  - BACKGROUND: Some positive therapeutic effects in fibromyalgia syndrome (FS) were
      reported with both tricyclic and new antidepressant drugs as well as serotonergic
      agents (5HT2 and 5HT3 receptor blockers). METHODS: In the present study, a novel
      antidepressant drug mirtazapine, 15-30 mg/day, has been used in 29 patients with
      FS in an open trial. RESULTS: Twenty-six patients completed the six-week study.
      Ten (38%) were considered responders on account of the reduction of > or =40% on
      pain, fatigue and sleep disturbances and remission of depressive symptoms at the
      end of study. Eighteen patients had at least moderate depression before
      mirtazapine treatment and 8 patients presented mild depressive symptoms.
      Reduction on main symptoms of FS after 6 weeks of mirtazapine treatment
      significantly correlated with the reduction in depression. However, the
      percentage of responders and patients with > or = 40% reduction on main symptoms
      of fibromyalgia was similar in high and low depression groups. CONCLUSIONS: The
      results obtained suggest that mirtazapine may be promising method of FS
      treatment. Further double-blind placebo-controlled studies are required to
      confirm these results.

PMID- 15467974
TI  - Differential effects of long-term treatment with clozapine or haloperidol on GABA
      transporter expression.
AB  - BACKGROUND: Post-mortem studies with brain samples of schizophrenic patients led
      revealed altered GABA-ergic markers like reduced expression of the GABA
      transporter GAT-1. Whether this effect is due to the pathophysiology of
      schizophrenia or to antipsychotic treatment has not been investigated. We
      therefore established an animal trial of long-term antipsychotic treatment to
      address this question. METHODS: A total of 33 adult male rats were investigated
      in three cohorts of 11 animals. One group received clozapine (45 mg/kg/ day),
      another group haloperidol (1.5 mg/kg/day), and the third one pH-adapted water
      over a period of 6 months. In situ hybridization with cRNA probes specific for
      GABA transporters VGAT, GAT-1 and GAT-3 were performed in comparison to control
      animals. RESULTS: While GAT-1 was upregulated, VGAT expression declined in
      cortical and limbic brain regions, whereby haloperidol showed a greater effect
      than clozapine. GAT-3 expression was suppressed in parietal and temporal cortex.
      CONCLUSIONS: We thus conclude that long-term antipsychotic treatment alters GABA
      transporter expression in rat. The upregulation of GAT-1 contrasts with the post
      mortem finding of reduced GAT-1 expression in schizophrenic patients. Our results
      facilitate the distinction between disease dependent changes of GABAergic markers
      and medication effects.

PMID- 15467975
TI  - High dose antipsychotic use in schizophrenia: findings of the REAP (research on
      east Asia psychotropic prescriptions) study.
AB  - BACKGROUND: High-dose antipsychotic regimes (defined as the prescription of more
      than 1000 chlorpromazine-equivalents milligrams of antipsychotic per day) in the
      management of patients with schizophrenia are not uncommon, but most reports are
      from western countries. Recent functional neuroimaging studies have found that
      the previous notion concerning the use of antipsychotic medication, especially in
      high doses, was unsupported and untenable. METHODS: This international study
      examined the use of high dose antipsychotic medication and its clinical
      correlates in schizophrenia patients within six East Asian countries/territories.
      RESULTS: Within the study group (n = 2399), 430 patients (17.9%) were prescribed
      high dose antipsychotics. Antipsychotic use varied significantly between
      countries, with Japan, Korea, and Singapore using higher doses than the other
      countries. High dose antipsychotic use was associated with younger age in Japan
      (p < 0.001), longer duration of admission (p < 0.001), duration of illness (p <
      0.001, particularly in Korea and Taiwan), positive psychotic symptoms (p < 0.001,
      particularly in Japan and Korea), and aggression (p < 0.05, particularly in
      Japan), and also with a higher likelihood of extrapyramidal and autonomic adverse
      effects (p < 0.05, particularly in China). Country, younger age, the presence of
      delusions and disorganized speech, polypharmacy, and receiving depot medication
      but not atypical antipsychotic drugs were important predictors of high
      antipsychotic use. CONCLUSIONS: This survey revealed that high antipsychotic
      dosing is not an uncommon practice in East Asia. It behooves the prescribing
      clinicians to constantly reevaluate the rationale for such a practice.

PMID- 15467976
TI  - Pharmacokinetics of m-chlorophenylpiperazine after intravenous and oral
      administration in healthy male volunteers: implication for the pharmacodynamic
      profile.
AB  - INTRODUCTION: Serotonin plays an important role in psychiatric diseases, most
      notably in depression and anxiety. Seven different major serotonin receptor
      subtypes have been described. Receptor-selective agonists and antagonists have
      been searched for to find a suitable drug to test the in vivo receptor
      sensitivity. Different serotonin receptor subtypes take part in the control of
      neuroendocrine function. m-Chlorophenylpiperazine (mCPP) acts as an agonist to
      serotonin 2C, 1A, 1B, and 1D receptor subtypes and is applied in challenge tests.
      The object of this study was to develop a pharmacokinetic-pharmacodynamic model
      to describe the effects of mCPP on pituitary hormone secretion. METHODS: The
      hormone and mCPP plasma concentrations were determined after intravenous and oral
      administration of mCPP to 12 healthy men. The kinetic parameters of mCPP were
      compared to the drug's effect on hormonal response. RESULTS: After mCPP
      treatment, ACTH, cortisol, and prolactin levels were significantly increased
      compared to placebo. There was also a significant increase in clinical response
      (anxiety, shivering, dizziness, heightened sensitivity toward light and noise,
      and fear of losing control). Maximum mCPP concentrations varied 2.3-fold after
      intravenous infusion and 8-fold after oral administration. The absolute
      bioavailability ranged from 12% to 84%. mCPP's elimination half-life ranged from
      2.4 h to 6.8 h after intravenous infusion and from 2.6 h to 6.1 h after oral
      application. However, the kinetic data as well as the pharmacodynamic response
      varied to an extent that precluded pharmacokinetic-pharmacodynamic modeling. The
      wide interindividual variability in mCPP's disposition kinetics could not be
      fully explained by genetic variation of the mCPP-metabolizing enzyme cytochrome
      P4502D6, which was determined in all probands. DISCUSSION: Other factors
      contributing to the variability in disposition kinetics could not be ruled out in
      this study, suggesting that mCPP is not a suitable model drug to test serotonin
      2C receptor activity in vivo.

PMID- 15467977
TI  - Usefulness of bromocriptine in the treatment of amisulpride-induced
      hyperprolactinemia: a case report.

PMID- 15467978
TI  - Tramadol use and dependence in chronic noncancer pain patients.

PMID- 15467979
TI  - The genetic or mythical ancestry of descent groups: lessons from the Y
      chromosome.
AB  - Traditional societies are often organized into descent groups called "lineages,"
      "clans," and "tribes." Each of these descent groups claims to have a common
      ancestor, and this ancestry distinguishes the group's members from the rest of
      the population. To test the hypothesis of common ancestry within these groups, we
      compared ethnological and genetic data from five Central Asian populations. We
      show that, although people from the same lineage and clan share generally a
      recent common ancestor, no such common ancestry is observed at the tribal level.
      Thus, a tribe might be a conglomerate of clans who subsequently invented a
      mythical ancestor to strengthen group unity.

PMID- 15467980
TI  - Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete
      sequencing: implications for the peopling of South Asia.
AB  - To resolve the phylogeny of the autochthonous mitochondrial DNA (mtDNA)
      haplogroups of India and determine the relationship between the Indian and
      western Eurasian mtDNA pools more precisely, a diverse subset of 75
      macrohaplogroup N lineages was chosen for complete sequencing from a collection
      of >800 control-region sequences sampled across India. We identified five new
      autochthonous haplogroups (R7, R8, R30, R31, and N5) and fully characterized the
      autochthonous haplogroups (R5, R6, N1d, U2a, U2b, and U2c) that were previously
      described only by first hypervariable segment (HVS-I) sequencing and coding
      region restriction-fragment-length polymorphism analysis. Our findings
      demonstrate that the Indian mtDNA pool, even when restricted to macrohaplogroup
      N, harbors at least as many deepest-branching lineages as the western Eurasian
      mtDNA pool. Moreover, the distribution of the earliest branches within
      haplogroups M, N, and R across Eurasia and Oceania provides additional evidence
      for a three-founder-mtDNA scenario and a single migration route out of Africa.

PMID- 15467981
TI  - Contractions of D4Z4 on 4qB subtelomeres do not cause facioscapulohumeral
      muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is associated with contractions of
      the D4Z4 repeat in the subtelomere of chromosome 4q. Two allelic variants of
      chromosome 4q (4qA and 4qB) exist in the region distal to D4Z4. Although both
      variants are almost equally frequent in the population, FSHD is associated
      exclusively with the 4qA allele. We identified three families with FSHD in which
      each proband carries two FSHD-sized alleles and is heterozygous for the 4qA/4qB
      polymorphism. Segregation analysis demonstrated that FSHD-sized 4qB alleles are
      not associated with disease, since these were present in unaffected family
      members. Thus, in addition to a contraction of D4Z4, additional cis-acting
      elements on 4qA may be required for the development of FSHD. Alternatively, 4qB
      subtelomeres may contain elements that prevent FSHD pathogenesis.

PMID- 15467982
TI  - Mutations in the AHI1 gene, encoding jouberin, cause Joubert syndrome with
      cortical polymicrogyria.
AB  - Joubert syndrome (JS) is an autosomal recessive disorder marked by agenesis of
      the cerebellar vermis, ataxia, hypotonia, oculomotor apraxia, neonatal breathing
      abnormalities, and mental retardation. Despite the fact that this condition was
      described >30 years ago, the molecular basis has remained poorly understood.
      Here, we identify two frameshift mutations and one missense mutation in the AHI1
      gene in three consanguineous families with JS, some with cortical polymicrogyria.
      AHI1, encoding the Jouberin protein, is an alternatively spliced signaling
      molecule that contains seven Trp-Asp (WD) repeats, an SH3 domain, and numerous
      SH3-binding sites. The gene is expressed strongly in embryonic hindbrain and
      forebrain, and our data suggest that AHI1 is required for both cerebellar and
      cortical development in humans. The recently described mutations in NPHP1,
      encoding a protein containing an SH3 domain, in a subset of patients with JS plus
      nephronophthisis, suggest a shared pathway.

PMID- 15467983
TI  - Evidence for sex-specific risk alleles in autism spectrum disorder.
AB  - We investigated the genetic aspects of the large sex bias in the prevalence of
      autism spectrum disorder by monitoring changes in linkage when the family set for
      an affected sibling pair genome scan is subdivided on the basis of the sex of
      affected children. This produces a significant excess in the total number of
      linkage peaks (P=1.3 x 10(-8)) and identifies a major male-specific linkage peak
      at chromosome 17q11 (P<.01). These results suggest that sexual dichotomy is an
      important factor in the genetics of autism; the same strategy can be used to
      explore this possibility in other complex disorders that exhibit significant sex
      biases.

PMID- 15467984
TI  - [Lumbar spinal surgery in elderly patients].
AB  - INTRODUCTION: In the geriatric population, pain with sciatic irradiation requires
      a differential diagnosis to enable a distinction to be made mainly between a
      herniated disc, lateral recess stenosis or lumbar stenosis. In addition, in many
      cases the degenerative problems are often associated with lumbar listhesis or
      instability. Furthermore, these patients present very diverse associated
      cardiovascular, pulmonary or metabolic pathologies which can make surgery
      complicated and, above all, prolong post-operative recovery, as well as
      increasing morbidity and mortality. PATIENTS AND METHODS: We reviewed a group of
      50 patients aged between 70 and 87 who had been submitted to surgery between 1997
      and 2003; 27 were females and 23 males. 76% of them presented associated systemic
      pathologies and 22% had a history of previous spinal surgery. In 15 cases
      clinical symptoms were gait disorders involving claudication, there were three
      cases of paraparesis with cauda equina syndrome, 19 lumbagos with bilateral
      sciatica and 16 cases of lumbago with unilateral sciatica. Unilateral
      decompression hemilaminectomy was performed in 16 patients (group I) with
      microdiscectomy in 13 cases, laminectomy of one or several vertebrae (group II)
      was carried out in 17 patients and another 17 patients were submitted to
      decompression laminectomy plus arthrodesis with transpedicular instrumentation
      (group III). RESULTS: Overall a significant improvement was observed in 86% of
      patients. Detected complications involved two serious deep infections (4%), one
      of which was secondary to cerebrospinal fluid fistula, and the other occurred in
      an instrumented patient. No instabilities secondary to the laminectomy were
      observed in non-instrumented patients. No intraoperative anaesthetic or surgical
      complications were produced. Patients are followed up simultaneously during the
      post-operative period by both Internal Medicine and Neurosurgery. CONCLUSIONS: In
      the geriatric population there is a high incidence of degenerative problems, not
      only involving canal stenosis but also herniated discs. Surgical intervention
      must be the least aggressive possible, bearing in mind that a laminectomy does
      not presuppose post-surgical stability. The associated pathologies presented by
      these patients make a good immediate post-operative follow-up indispensable if
      morbidity and mortality rates are to be reduced.

PMID- 15467985
TI  - [Factors affecting the arrival time of cerebrovascular disease patients at the
      emergency department of a Peruvian hospital].
AB  - INTRODUCTION: The implementation of stroke units and of thrombolysis as treatment
      in cerebrovascular disease (CVD) brought about a radical change in its
      management, but which is influenced by the time patients take to reach the health
      centre following the onset of symptoms. AIMS: This study seeks to determine the
      time needed by CVD patients to reach the Emergency Department at the Hospital
      Nacional Guillermo Almenara Irigoyen (HNGAI) and to establish the sociocultural
      and cultural factors that can affect it. PATIENTS AND METHODS: We carried out a
      prospective study of 186 patients diagnosed as suffering from CVD on urgent
      admission to the HNGAI. Both the time lapsed between the onset of symptoms and
      the sociocultural and cultural factors of the patient and the person accompanying
      them were determined. Patients were divided into two groups: those with a short
      arrival time (< 3 hours) and those who took longer (> 3 hours); statistically
      significant differences were found in the factors under study. RESULTS: The mean
      time taken to reach Emergency was 22 h 57 min 19 s; 22.58% had a short arrival
      time; the predominant socioeconomic factors were the degree of primary schooling
      (49.46%), being a pensioner (44.1%), living in company (94.6%) and recognition of
      the symptoms (36.6%); the most commonly used means of transport were taxi
      (47.31%) and ambulance (45.16%). The person who accompanied them had a higher
      (44.09%) or secondary (43.01%) education, was employed (33.3%), and recognised
      the symptoms (65.6%). CONCLUSIONS: An important number of CVD patients (22.58%)
      reach the Emergency Department shortly after the onset of symptoms. Recognition
      of the symptoms by the person accompanying the patient and taking them to
      hospital by taxi are linked to early arrival, which are factors that should be
      taken into account when implementing an stroke unit in our area.

PMID- 15467986
TI  - [Characterisation of the influence exerted by the visual factor in patients with
      balance disorders].
AB  - INTRODUCTION: Visual information provides data about the position and movement of
      the head with respect to objects and serves as a source of reference for the
      proper perception of verticality. It also plays a specific role in postural
      control by modifying the efficiency of the vestibular and proprioceptive
      responses. AIMS: Our aim was to determine how visual information interacts with
      the symptoms of patients with vertigo, dizziness or instability and to find out
      the degree of disability it produces. PATIENTS AND METHODS: A study was conducted
      in 200 patients who had visited because of dizziness, vertigo, instability or
      loss of balance. We analysed the aspects related to the clinical symptoms of the
      patients. First, we examined the influence visual stimuli have on the symptoms of
      vestibular disease itself and their repercussions on the situation between
      crises. Second, the degree of disability was evaluated on the specific DHI
      (Dizziness Handicap Inventory) questionnaire. RESULTS: As regards the influence
      exerted by visual stimulation on the main symptoms, 77.5% reported that it had no
      effect and 21% said that it made them worse. With regard to the influence of
      visual stimulation during the intercritical period, it was of no relevance in
      53.5% of patients, 26.5% were unaffected, it had an exacerbating effect in 4% and
      in 7.5% it induced it. Different disorders were observed depending on the type of
      disease suffered by the patient, and disability was greater according to the
      influence exerted by the visual factor. CONCLUSIONS: Postural adjustments induced
      by visual stimuli are capable of triggering instability with serious
      consequences.

PMID- 15467987
TI  - [Analysis of the interference pattern in patients with muscular dystrophy].
AB  - INTRODUCTION: The conventional electromyography contribute to differentiation of
      myopatic and neuropatic patterns in neuromuscular disorders, however, the
      classical patterns related to myopatic changes can result in neurogenic
      components, this confusion could be due to denervation and reinervation changes
      involved at the different stages of those diseases. OBJECTIVE: Demonstrate the
      importance of quantitative electromyographic techniques, as the interference
      pattern analysis (IPA), for a better differentiation of muscular dystrophies.
      PATIENTS AND METHODS: IPA was done in 95 patients with 3 different muscular
      dystrophies: 52 Duchenne muscular dystrophy (DMD), 33 limb girdle muscular
      dystrophy (LGMD) and 10 myotonic muscular dystrophy (MD) individuals and in a
      control group of 25 individuals. The left braquial biceps and right anterior
      tibial muscles were evaluated; the variables analyzed were turns/seconds (t/s),
      amplitude/turns (a/t), ratio turns/amplitude mean and root squared mean (RSM).
      RESULTS: We found statistical significant differences in all variables in both
      braquial biceps and right anterior tibial muscles (p < 0.05) in DMD patients. In
      LGMD we only found differences in a/t in braquial biceps. In MD the differences
      were observed in a/t, ratio and RSM in braquial biceps, and in a/t (in anterior
      tibial). CONCLUSIONS: All the DMD patients show differences in IPA values in
      relation to control group, MD only in biceps, However there were not important
      changes in LGMD probably because the diversity and lack of homogeneity in
      affected muscles in this group.

PMID- 15467988
TI  - [Event-related potentials and the diagnosis of short-term verbal memory disorders
      in cerebrovascular disease].
AB  - INTRODUCTION: Cerebrovascular disease can cause different memory disorders
      depending on the area of the brain involved. More specifically, ischemic lesions
      in the frontal region can be associated to short-term verbal memory disorders.
      PATIENTS AND METHODS: Two groups of subjects were studied, 10 of whom were
      patients who presented a frontal cerebral infarction and 10 healthy controls.
      They were administered a memory task involving word recognition. While they were
      performing the task the electrical activity of their brains was recorded in order
      to examine event-related potentials (ERP). RESULTS: The patients' performance of
      the task was poorer than that of the healthy control subjects. Likewise, while
      the latter displayed a predominantly frontal distribution of ERPs, in the
      patients the frontal activity diminished and was seen to be chiefly
      temporoparietooccipital. CONCLUSIONS: These findings allow important conclusions
      to be drawn about the characteristics of the memory disorder presented by these
      patients.

PMID- 15467989
TI  - [Hereditary sensory and autonomic neuropathies. The neurophysiological and
      pathological aspects of two cases with congenital insensitivity to pain].
AB  - AIM: Two patients suffering from congenital insensitivity to pain were studied.
      They corresponded to types IV and V of the 'hereditary sensory and autonomic
      neuropathies' (HSAN) classification. CASE REPORTS: The first case showed
      important autonomic dysfunctions, such as anhidrosis, hyperthermia, skin and bone
      trophic impairment, and mental retardation; the second one only exhibited
      alterations in pain and temperature sensibilities. In both, chronic indolent
      corneal ulcers were also present. Conventional neurophysiological evaluation of
      the neuromuscular system was normal, but an afferent disturbance of the blink
      reflex (BR) was evident in both. The sympathetic skin response was absent in the
      HSAN type IV case and normal in the HSAN type V. Notable reduction of the small
      myelinated fibres, associated to almost no unmyelinated fibres in the first case,
      were found in the sural nerve biopsies. CONCLUSIONS: So far there haven't been
      described BR abnormalities in patients with congenital insensitivity to pain,
      which should be related to a trigeminal sensory impairment, which could explain
      the corneal ulcers that suffered these cases. BR studies should be included in
      the neurophysiological evaluation of the suspected small fibre neuropathies even
      when there are no facial symptoms shown.

PMID- 15467990
TI  - [Intracranial haemorrhage secondary to a lightning strike: a case report].
AB  - INTRODUCTION: The damage caused to the central nervous system by lightning can be
      immediate or delayed. Cerebrovascular accidents are usually an infrequent
      complication of lightning strikes. CASE REPORT: We report the case of a patient
      who was hit by lightning and then developed an acute bilateral
      intraparenchymatous haemorrhage in the basal ganglia and the left internal
      capsule. DISCUSSION: Few cases of intracranial haemorrhages secondary to
      lightning strikes have been reported. We carry out a review and analysis of the
      literature currently available on the subject. A number of theories have been put
      forward that attempt to explain the mechanism behind these haemorrhages in
      patients who have been hit by lightning. The reason why there is a predilection
      for the basal ganglia is unknown, although it could be linked to the particular
      features of the vascularisation of the area.

PMID- 15467991
TI  - [Cerebral venous thrombosis associated to subacute De Quervain's thyroiditis in a
      carrier for the G20210A mutation of the prothrombin gene].
AB  - INTRODUCTION: Recently, thyrotoxicosis has been described as a risk factor for
      cerebral venous thrombosis (CVT) in some reported cases. We present a case of CVT
      associated to a subacute De Quervain's thyroiditis in a young female who was an
      heterozygous carrier for the G20210A mutation of the prothrombin gene. CASE
      REPORT: A 42-year-old female with irrelevant past medical history developed a
      thrombosis of the superior sagital and right transverse sinus in the initial
      phase of a subacute thyroiditis. Diagnosis was made by thyroid radioactive iodine
      uptake, and cerebral computerized tomography scan, magnetic resonance imaging,
      and magnetic resonance angiography. Treatment with aspirin and corticosteroids
      was started until thyroid function was normalized. When CVT diagnosis was made,
      the patient was treated with anticoagulation. Two months later, magnetic
      resonance imaging showed resolution of the CVT. The patient was diagnosed as an
      heterozygous carrier for the G20210A mutation of the prothrombin gene by genetic
      studies. CONCLUSIONS: Subacute thyroiditis might act as a risk factor for CVT,
      increasing the thrombotic risk in the presence of other acquired or hereditary
      prothrombotic factors, such as the G20210A mutation of the prothrombin gene in
      our patient.

PMID- 15467992
TI  - [Restless legs syndrome in a patient with amputation of both legs].
AB  - INTRODUCTION: We present the case of a patient who, after amputation of both
      legs, suffered restless legs syndrome (RLS). This syndrome is characterised by a
      feeling of agitation in the legs and an overwhelming need to move them. CASE
      REPORT: A 62-year-old male patient who visited because of sleep onset and
      maintenance insomnia. The aetiology of the insomnia was interpreted as being an
      anxiety-dysthymic syndrome, which improved with suitable medication. Five months
      later, the patient returned with the same symptoms (onset insomnia). On
      questioning the patient again, we noticed that he displayed clear symptoms of
      RLS, despite the absence of both lower limbs. The clinical features were resolved
      with the administration of ropinirole. CONCLUSIONS: We do not know of any similar
      cases, but the scarce amount of knowledge available about RLS makes it likely
      that many patients with amputations present this problem without any proper
      diagnosis.

PMID- 15467993
TI  - [Serotonergic control of prefrontal cortex].
AB  - INTRODUCTION AND DEVELOPMENT: The prefrontal cortex (PFC) plays a crucial role in
      higher brain functions such as working memory or cognition and controls, via the
      excitatory axons of pyramidal neurons, the activity of many subcortical motor and
      limbic areas. It receives a dense innervation from the brainstem aminergic
      nuclei, including the serotonergic raphe nuclei. Prefrontal function and
      metabolism is altered in patients with severe psychiatric disorders, like major
      depression or schizophrenia. Although the exact role of serotonergic
      neurotransmission in PFC remains largely unknown, the PFC contains a very large
      density or serotonin 5-HT1A (inhibitory) and 5-HT2A (excitatory) receptors. In
      addition, hallucinogens like LSD or DOI are agonists and atypical antipsychotics
      are antagonists at 5-HT2A receptors. In this review we focus on the main
      excitatory and inhibitory mechanisms through which serotonin modulates pyramidal
      and GABAergic neuron activity in the PFC. CONCLUSIONS: We report on the presence
      of 5-HT1A and 5-HT2A receptor-mediated responses in pyramidal neurons of the PFC
      that exert opposite effects on their activity when recorded in vivo in the
      anesthetized rat. Despite the large co-expression of both receptors in pyramidal
      neurons of the PFC, physiological amounts of 5-HT mainly inhibit pyramidal
      neurons. This is probably due to the distinct location of 5-HT1A and 5-HT2A in
      pyramidal neurons. Thus, 5-HT1A receptors are mainly localized in the axon
      hillock, where they may have a prominent inhibitory role in the control of
      pyramidal activity given their coupling to GIRK channels. Moreover, 5-HT can
      inhibit pyramidal neurons indirectly through the activation of 5-HT2A and 5-HT3
      receptors localized in GABAergic interneurons and a subsequent increase in
      synaptic GABA inputs.

PMID- 15467994
TI  - [Ability of neonatal head circumference to predict long-term neurodevelopmental
      outcome].
AB  - AIM: We review the ability of head circumference (HC) at birth and head growth
      during the neonatal period to predict neurodevelopmental outcome, putting
      emphasis on new knowledge in this area. DEVELOPMENT: During infancy HC correlates
      closely with intracranial volume and constitutes an accurate predictor of
      cerebral volume. Both an abnormal head size at birth and an abnormal head growth
      during the neonatal period, can express brain damage or the presence of entities
      that involve varied degrees of neurological dysfunction in childhood. In general,
      the influence of head size or growth abnormalities on neurodevelopment is more
      related to the underlying etiology and/or the presence of structural diseases of
      the brain than with the HC alteration itself. HC evaluation is of particular
      interest in sick neonates, specially very low birth weight infants, regardless of
      whether they are normal or small for gestational age, and both during admission
      an during the first months of life. In these patients, HC catch-up within the
      first months of life represents a favorable neurodevelopmental prognostic factor.
      CONCLUSION: HC measuring and head growth evaluation constitute the most simple,
      inexpensive and quick available tools to assess the development of the central
      nervous system and identify neonates at risk of neurodevelopmental disorders.

PMID- 15467995
TI  - [Central chemoreceptors and sudden infant death syndrome].
AB  - INTRODUCTION: Carbon dioxide partial pressure and pH in the extracellular
      compartment are the most powerful signals regulating respiration. Central
      chemoreceptors (QC) undergo the stimulating effect of CO2 and pH upon
      respiration. AIMS: This review tries to provide an actual envision of the
      progress in the knowledgement on central chemoreception. It also tries to
      highlight the importance of the alterations in the chemoreception mechanism as a
      cause of sudden infant death syndrome (SIDS). DEVELOPMENT: Central chemoreceptors
      respond to acid-base imbalance acting on neurons that give rise to the central
      breathing pattern and have the ability to change the respiratory rate, which is
      normally needed to restore the normal values of acid-base status. QC are widely
      distributed in the brain stem, however QC neurons in the ventral surface of the
      medulla like to be the main relays for ventilatory responses after acid-base
      stimulation. CONCLUSIONS: It has been shown that QC are sensitive to pH and CO2
      as in vivo as in vitro conditions, most of them being serotonin immunopositive, a
      neurotransmitter with known effects on breathing pattern. By other side,
      alterations of central chemoreception have been associated to pathologies like
      congenital hypoventilatory syndrome or SIDS. Interestingly, the post mortem exams
      of the brain of infants dead because these syndromes have showed anomalies of
      serotonergic receptor located in regions containing QC neurons and in others
      related with cardiorespiratory integration.

PMID- 15467996
TI  - [Molecular diffusion/cerebrospinal fluid flow theory].
AB  - AIM: To review the fundamental aspects of the theory of the molecular flow/
      cerebrospinal flux described recently and it can explained a group of events in
      the physiology of the cerebrospinal fluid and the physiopathology of neurological
      diseases. DEVELOPMENT: This theory was based on the postulate that a decrease of
      the flux rate of the cerebrospinal fluid was accompanied by an increment of the
      protein concentration in it and in the nervous system tissue. The increment of
      the protein transport from the blood to the cerebrospinal fluid not require
      structural changes or an increase of permeability. The reibergram or Reiber's
      quotient diagram, with the discriminatory hyperbolic function with its
      theoretical basis and its clinical relevance confirm the acceptance of the
      present theory. This theory was based on the first and second Fick's diffusion
      laws The increment of the molecular diffusion is the cause of the non-linear
      decrease of the cerebrospinal flux rate because of the blood-cerebrospinal fluid
      barrier dysfunction. CONCLUSIONS: This theory explain that an increase of the
      albumin quotient does not means a morphologic change on the barrier structures.
      The change in the cerebrospinal flux rate it has been considered the principal
      modulator of the protein concentration in cerebrospinal fluid in pathological
      conditions characterized by a blood-cerebrospinal fluid barrier dysfunction.

PMID- 15467997
TI  - [The new antiepileptic drugs: their indications and side effects].
AB  - INTRODUCTION: Although the significant progress in pharmacotherapy of epilepsy
      during last decade was achieved, about one third of patients are resistant to the
      current treatment. The introduction of numerous effective, well tolerated and
      safe new antiepileptic drugs (AEDs) in the last decade of the 20th century has
      widened the choice of treatment options in epilepsy and improved the tolerability
      and the ease of use of treating patients with epilepsy. Nevertheless, significant
      safety and efficacy deficits continue to exist. Severe idiosyncratic reactions
      and organ toxicity have hampered the wide use of some of the newer AEDs. As a
      decade before, about one third of patients with chronic epilepsy is resistant to
      current pharmacotherapy. Even in patients in whom pharmacotherapy is efficacious,
      current AEDs do not seem to affect the progression or the underlying natural
      history of epilepsy. DEVELOPMENT: The revision of newer AEDs are formulation,
      action, doses and side effects. CONCLUSION: Thus, there is an unmet need for
      safer and more effective drugs, especially for chronic, drug-resistant epilepsy.
      To stimulate the development of even better compounds, the demonstrated benefits
      and risks of current new AEDs are reviewed.

PMID- 15467998
TI  - [From empiricism to neuroscience in Alzheimer's disease].
AB  - INTRODUCTION AND DEVELOPMENT: It has been almost a hundred years since
      neurofibrillar degeneration in the neurones of the cerebral cortex was first
      described by Alois Alzheimer. This finding led to the recognition of a new
      disease (a presenile dementia unlike senile dementia) using the
      clinicopathological empirical method employed at that time. Despite Alzheimer's
      own opinion and the subsequent findings from many neuropathological studies,
      general acknowledgement of the full implications of this dichotomy has taken
      decades. All the cases were grouped under the eponym of Alzheimer's disease and
      it is now being studied with the different modern scientific methods currently
      available to researchers. CONCLUSIONS: Alzheimer's disease has given rise to an
      exceptional associationist movement around the world and has become one of
      leading social and health problems facing the human race; its research and
      treatment will require the involvement of national and supranational public
      authorities.

PMID- 15467999
TI  - [Extensive cerebral infarction and neurocysticercosis].

PMID- 15468001
TI  - [Neurocysticercosis in Costa Rican children: clinical experience and the
      importance of epidemiological surveillance].

PMID- 15468002
TI  - [Posterior reversible encephalopathy in a 12-year-old female with nephrotic
      syndrome and methylprednisolone therapy].

PMID- 15468003
TI  - [Neurotoxicity in treatment with lithium. A case report and EEG findings].

PMID- 15468004
TI  - [Use of brain SPECT imaging in the diagnosis of Wernicke-Korsakoff's
      encephalopathy].

PMID- 15468005
TI  - [The long-term evolution of botulinum toxin dosage in the treatment of hemifacial
      spasms].

PMID- 15468007
TI  - [Multiple cerebral haemorrhages and antiplatelet drugs].

PMID- 15468008
TI  - Antiparasitic activity of an ivermectin and praziquantel combination paste in
      horses.
AB  - Modern anthelmintic use in horses has decreased the prevalence of the large
      strongyles, which has in turn shifted the focus of parasitologists to the
      pathogenic importance of the small strongyles, tapeworms, and other parasites.
      These studies show that a combination product containing ivermectin and
      praziquantel allowed efficacious treatment of horses for nematode, cestode, and
      bot infections. The use of this combination product may be of special benefit to
      horses that are mainly kept outdoors and on grazing pastures.

PMID- 15468009
TI  - Effect of preoperative administration of tepoxalin on hemostasis and hepatic and
      renal function in dogs.
AB  - Preemptive analgesia is an important part of surgical management, but some NSAIDs
      can adversely affect platelet function or renal or hepatic status. Tepoxalin is
      approved in the United States for control of pain and inflammation associated
      with arthritis and in Europe for relief of pain caused by musculoskeletal
      disorders. In this study, no significant effects on indices of hemostasis or
      renal or hepatic function were detected when a single preoperative oral dose of
      tepoxalin was administered to young healthy dogs undergoing anesthesia and
      surgery.

PMID- 15468010
TI  - Double-blinded placebo-controlled clinical field trial to evaluate the safety and
      efficacy of topically applied 1% diclofenac liposomal cream for the relief of
      lameness in horses.
AB  - A topical 1% diclofenac liposomal cream proved to be safe, easy to use, and
      effective in reducing equine lameness caused by degenerative joint disease.
      Diclofenac liposomal cream was shown to reduce lameness as graded by owners and
      veterinarians, regardless of the severity or chronicity of the clinical
      condition. Topical application allowed for more convenient administration than
      oral or injectable agents, and no clinically relevant hematologic or serum
      biochemical changes were noted. The liposomal cream provided a delivery system
      for diclofenac, an NSAID, to achieve therapeutic levels locally with decreased
      risk for systemic toxicity and side effects and improved targeting of the painful
      area.

PMID- 15468011
TI  - Biology and control of ticks infesting dogs and cats in North America.
AB  - At least 15 different infectious agents and diseases are transmitted or produced
      by ticks parasitizing dogs and cats in North America. Those infectious agents and
      diseases are distributed among eight different tick species that commonly infest
      dogs and cats. All but one of these species are hard ticks with a three-host
      development cycle in which each motile stage (larva, nymph, and adult) feeds on a
      different host after molting. Tick species, disease occurrence, and peak activity
      of each tick life stage can vary dramatically depending on geographic and
      climatic conditions. Gaining an understanding of tick distribution, tick ecology,
      and seasonal occurrence of different tick life stages can help with the
      management of tick infestations and reduce the incidence of tick-transmitted
      diseases in dogs and cats. Control should be based on an understanding and
      management of ecologic factors responsible for tick infestations and selection of
      appropriate acaricides. Occasionally, topical acaricides will appear not to have
      prevented tick infestations. This lack of control may be real or perceived based
      on reinfestation rates and/or pet owner expectations of product performance.

PMID- 15468012
TI  - Pharmacokinetics, stability, and retrospective analysis of use of an oral gel
      formulation of the bovine injectable enrofloxacin in horses.
AB  - In many cases of equine infectious disease, long-term administration of
      antimicrobial drugs is required. Oral agents are preferred because of the
      relative ease of administration compared with other routes. Enrofloxacin has been
      shown to be effective against a variety of equine pathogens, but oral
      administration of this drug has proved difficult in horses. An oral gel
      formulation made from the injectable cattle product produces blood levels
      sufficient to resolve infections caused by a variety of common equine pathogens.

PMID- 15468013
TI  - Aging with a spinal cord injury: factors associated with the need for more help
      with activities of daily living.
AB  - OBJECTIVES: To determine (1) the frequency of the need for more help with
      activities of daily living (ADLs), (2) the frequency of medical complications,
      and (3) the association between medical, injury-related, and sociodemographic
      factors and the need for more help with ADLs among those aging with spinal cord
      injury (SCI). DESIGN: Cross-sectional survey. SETTING: General community,
      international. PARTICIPANTS: Volunteers (N=352) with SCI for more than 20 years.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The need for more help with
      ADLs. RESULTS: The need for more help with ADLs during the last 3 years was
      reported by 32.1% of participants. At least 1 medical complication was reported
      by 85%. Constipation (47.9%), diarrhea/bowel accidents (41.8%), and pressure
      ulcers (38.7%) were common. Constipation, pressure ulcers, female gender, and
      years postinjury were associated with needing more help with ADLs. Constipation
      and pressure ulcers were associated with a 97% and a 76% increase, respectively,
      in the likelihood of needing more help with ADLs during a 3-year time period.
      Female gender was associated with a 96% increased odds of needing more help with
      ADLs. There was a 42% increased odds of needing more help with ADLs per decade
      after SCI. CONCLUSIONS: People aging with SCI are vulnerable to medical
      complications, and additional help is required to function. Knowledge of the
      effect of these factors, particularly the tetrad of constipation, pressure
      ulcers, female gender, and number of years postinjury, should increase awareness
      that more help with ADLs may be needed over time.

PMID- 15468014
TI  - Attending to the task: interference effects of functional tasks on walking in
      Parkinson's disease and the roles of cognition, depression, fatigue, and balance.
AB  - OBJECTIVE: To evaluate the interference effects on walking of functional
      activities in the home in people with Parkinson's disease (PD) and the
      contribution of clinical symptoms to disturbance of gait. DESIGN: A repeated
      measures trial, using a dual-task paradigm to evaluate the attentional demands of
      functional activities. SETTING: Participants' homes and a clinic. PARTICIPANTS:
      Twenty subjects with idiopathic PD and 10 age-, sex-, and education-matched
      controls. INTERVENTIONS: Subjects performed a simple walking task, a dual-motor
      task, a dual-cognitive task, and a multiple task, all of which were real-world
      activities. Main outcome measures Walking speed, mean step length, and step
      frequency were compared across different tasks for each subject. A battery of
      clinical outcome measures hypothesized to compete for attention were also
      conducted: cognition (Hayling and Brixton tests), anxiety and depression
      (Hospital Anxiety and Depression test), fatigue (Multidimensional Fatigue
      Inventory), balance (Berg Balance Scale), and disease severity (Hoehn and Yahr
      score). RESULTS: PD subjects walked at a significantly slower speed (26.5%,
      P<.001) and reduced step length (23%, P<.001) than did the controls. Performance
      of a concurrent cognitive and multitask resulted in significantly slower gait
      speed (P=.022; P<.015) and reduced mean step length (P=.022; P=.001) in PD
      subjects. Cognitive function, depression, physical fatigue, and balance were
      significantly related to walking speed for the functional tasks. Multiple
      regression analysis showed that the Brixton test, physical fatigue, and
      depression accounted for up to 39% of the variation in walking speed during
      functional tasks in PD and control subjects and balance accounted for 54% of
      variance for walking in PD subjects. CONCLUSIONS: Competition for attention
      through additional activities, decreased executive function, depression, fatigue,
      and impaired balance will increase difficulty in walking for PD subjects.
      Evaluation of performance during complex functional activities in an appropriate
      environment should be a focus of therapeutic assessment. Furthermore, functional
      performance may be influenced by several other symptoms that should also be
      considered.

PMID- 15468015
TI  - Kinesiophobia in chronic fatigue syndrome: assessment and associations with
      disability.
AB  - OBJECTIVES: To investigate aspects of the validity of the total scores of the
      Tampa Scale for Kinesiophobia (TSK), Dutch Version, which was modified to make it
      an appropriate questionnaire for the assessment of kinesiophobia (fear of
      movement) in chronic fatigue syndrome (CFS) patients (the Dutch TSK-CFS), and,
      using this assessment tool, to examine the associations between kinesiophobia,
      exercise capacity, and activity limitations and participation restrictions in
      patients with CFS. DESIGN: Prospective observational studies. SETTING: An
      outpatient fatigue clinic. PARTICIPANTS: In the first study, 40 patients
      fulfilling the 1994 US Centers for Disease Control and Prevention (CDC) criteria
      for CFS were enrolled. The sample of the second study consisted of 51 CDC-defined
      patients with CSF. INTERVENTIONS: Not applicable. Main outcome measures Study 1:
      Subjects completed a set of questionnaires; the Utrechtse Coping List (UCL), the
      Dutch TSK-CFS, and the Dutch Baecke Questionnaire of Habitual Physical Activity.
      Study 2: All patients completed 2 questionnaires (Chronic Fatigue Syndrome
      Activities and Participation Questionnaire [CFS-APQ], Dutch TSK-CFS) and
      performed a maximal exercise stress test on a bicycle ergometer. The heart rate
      was monitored continuously by use of an electrocardiograph. Metabolic and
      ventilatory parameters were measured through spirometry. RESULTS: Study 1: The
      Cronbach alpha coefficient for the individual item scores on the TSK-CFS was .80.
      The total scores on the Dutch TSK-CFS showed a statistically significant
      correlation with both the avoidance/abide subscale of the UCL (Spearman rho=.35,
      P=.029) and the total score of the Baecke Questionnaire (rho=-.45, P=.004). Study
      2: The total scores on the Dutch TSK-CFS showed a statistically significant
      correlation with the total scores on the CFS-APQ (rho=.39, P=.004). No
      statistically significant associations were observed between the exercise
      capacity parameters and the total scores on the Dutch TSK-CFS. CONCLUSIONS: These
      results provide evidence for the internal consistency and the convergent and
      congruent validity of the scores obtained by use of the Dutch TSK-CFS.
      Kinesiophobia appears to be associated with activity limitations/participation
      restrictions but not with exercise capacity in patients with CFS.

PMID- 15468016
TI  - The influence of Tai Chi training on the center of pressure trajectory during
      gait initiation in older adults.
AB  - OBJECTIVE: To determine if a program of intense Tai Chi exercise that has been
      shown to reduce the risk of falling in older adults improves postural control by
      altering the center of pressure (COP) trajectory during gait initiation. DESIGN:
      Before-after trial. SETTING: Biomechanics research laboratory. PARTICIPANTS:
      Twenty-eight older adults transitioning to frailty who participated in either a
      48-week intervention of intense Tai Chi training or a wellness education (WE)
      program. INTERVENTIONS: Eight Tai Chi forms emphasizing trunk rotation, weight
      shifting, coordination, and narrowing of lower-extremity stance were taught twice
      weekly. WE program participants met once a week and received lectures focused on
      health. Main outcome measures The COP was recorded during gait initiation both
      before and after the 48-week intervention by using a forceplate sampling at 300
      Hz. The COP trajectory was divided into 3 periods (S1, S2, S3) by identifying 2
      landmark events. Displacement and average velocity of the COP trace in the
      anteroposterior (x) and mediolateral (y) directions, as well as smoothness, were
      calculated. RESULTS: Tai Chi training increased the posterior displacement of the
      COP during S1 and improved the smoothness of the COP during S2. CONCLUSIONS: Tai
      Chi improved the mechanism by which forward momentum is generated and improved
      coordination during gait initiation, suggesting improvements in postural control.

PMID- 15468017
TI  - Significance of poor patient participation in physical and occupational therapy
      for functional outcome and length of stay.
AB  - OBJECTIVES: To determine the frequency of poor patient participation during
      inpatient physical (PT) and occupational therapy (OT) sessions and to examine the
      influence of poor participation on functional outcome and length of stay (LOS).
      DESIGN: Prospective observational study. SETTING: University-based, freestanding
      acute rehabilitation hospital. PARTICIPANTS: Two hundred forty-two inpatients,
      primarily elderly (age range, 20-96y), with a variety of impairment diagnoses
      (eg, stroke), who were admitted for inpatient rehabilitation. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: The Pittsburgh Rehabilitation Participation
      Scale, the 13 motor items from the FIM instrument (FIM motor), LOS, and discharge
      disposition. RESULTS: We categorized the sample into 3 groups: "good"
      participators were those for whom all inpatient PT and OT sessions were rated 4
      or greater (n=139), "occasional poor" participators were those with less than 25%
      of scores rated below 4 (n=53), and "frequent poor" participators were those with
      25% or more of scores rated below 4 (n=50). Change in FIM motor scores during the
      inpatient rehabilitation stay was significantly better for good and occasional
      poor participators, compared with frequent poor participators (mean FIM
      improvement: 23.2, 22.8, and 17.6, respectively; repeated-measures analysis of
      variance group by time interaction, P <.002). LOS was significantly longer for
      occasional poor participators, compared with good and frequent poor participators
      controlling for admission FIM differences (adjusted means: 13.9d, 11.0d, and
      10.9d, respectively; analysis of covariance, P <.001). CONCLUSIONS: Poor
      participation in therapy is common during inpatient rehabilitation and has
      important clinical implications, in terms of lower improvement in FIM scores and
      longer LOS. These results suggest that poor inpatient rehabilitation
      participation and its antecedents deserve further attention.

PMID- 15468018
TI  - Rehabilitation outcomes in cognitively impaired patients admitted to skilled
      nursing facilities from the community.
AB  - OBJECTIVE: To examine the outcomes of patients with varying levels of cognitive
      impairment who received rehabilitation in skilled nursing facilities (SNFs).
      DESIGN: A retrospective analysis of the records of people admitted to SNFs for
      rehabilitation. SETTING: Seven SNFs in Colorado. PARTICIPANTS: Community-dwelling
      persons (N=7159), 65 years of age and older, admitted for rehabilitation after a
      hospitalization or decline in function between May 1998 and May 2002.
      Interventions Not applicable. MAIN OUTCOME MEASURES: Cognitive impairment was
      assessed using a 4-level categorization of the FIM instrument cognitive score at
      admission. Functional gain was measured using the FIM. Community discharge was
      measured as the proportion of patients discharged to home, board and care, or
      assisted living facility. Rehabilitation progress was measured as the number of
      FIM points gained per day. RESULTS: Significant functional gains were made during
      rehabilitation in motor and cognitive FIM scores, regardless of cognitive
      impairment. The most cognitively impaired patients required more rehabilitation
      intervention, achieved less FIM gain, and were less likely to be discharged to
      the community. The strongest predictors of FIM gain were the amount of therapy
      hours and admission cognitive FIM score. The strongest predictors of discharge to
      the community were the discharge total FIM score and age. The strongest
      predictors of adequate rehabilitation progress were medical complexity and
      admission cognitive FIM score. CONCLUSIONS: Patients with cognitive impairment
      were able to recover function with rehabilitation intervention. Patients with a
      more serious cognitive impairment received more rehabilitation intervention than
      patients with less impairment. Outcomes were predicted by admission and
      rehabilitation measures that were qualitatively different from other discharge
      outcomes. Health care professionals need to consider these factors as they create
      a rehabilitation plan of care for patients with cognitive impairment.

PMID- 15468019
TI  - Longitudinal changes in exercise capacity after stroke.
AB  - OBJECTIVE: To determine if stroke patients without specific aerobic training
      experience a change in the first 6 months after stroke. DESIGN: Descriptive,
      longitudinal study with repeated measures of exercise capacity at 1, 2, 3, and 6
      months after stroke. SETTING: Exercise testing laboratory in a tertiary care
      hospital. PARTICIPANTS: Consecutive sample of 25 patients (mean age +/- standard
      deviation, 64.1+/-13.6 y) 1 month after first ischemic stroke. INTERVENTIONS: Not
      applicable. Main Outcome Measures Peak oxygen consumption (Vo(2)peak) was
      measured by open-circuit spirometry during maximal effort treadmill walking with
      15% body-weight support. RESULTS: Mean Vo(2)peak increased from 14.8+/-5.3 mL x
      kg(-1). min(-1) at 1 month to 17.3+/-7.0 mL x kg(-1).min(-1) at 6 months after
      stroke (P=.003) or from 61.7%+/-16% to 71.3%+/-23% of age- and sex-related
      normative values for sedentary healthy adults (P=.008). CONCLUSIONS: Despite
      improvements in Vo(2)peak and other indices of cardiovascular training between 1
      and 6 months poststroke, substantial limitations in exercise capacity persisted.
      Further study is needed to determine the extent to which these limitations can be
      modified through aerobic conditioning.

PMID- 15468020
TI  - Rehabilitation of reaching after stroke: task-related training versus progressive
      resistive exercise.
AB  - OBJECTIVE: To evaluate the effectiveness of 2 rehabilitative approaches for
      improving paretic limb reaching by chronic stroke subjects. DESIGN: Pre- and
      posttest reaching to targets ipsilateral, midline, and contralateral to the
      impaired side. SETTING: Training in subjects' homes; testing in a laboratory
      setting. PARTICIPANTS: Twelve poststroke volunteers were matched using the Motor
      Assessment Scale (MAS) and then were randomly assigned to 1 of 2 training
      conditions. Subjects were subsequently categorized as at a high or low functional
      level, using the reaching pretest movement time scores. INTERVENTIONS: Training
      (trunk unrestrained) using the paretic limb was 4 weeks (12 sessions). Task
      related training (TRT) involved reaching to objects placed across the workspace.
      Progressive resistive exercise (PRE) involved whole-arm pulling against resistive
      therapeutic tubing in planes and distances similar to that in TRT. Main outcome
      measures Kinematic analysis of arm trajectory and trunk motion using the Peak
      Performance System, as well as scores on the MAS and the Rivermead Motor
      Assessment (RMA). RESULTS: For low-level groups, TRT resulted in increased
      substitutive trunk use at the target ipsilateral to the moving arm, and for
      midline and contralateral targets after PRE. Only low-level, TRT subjects
      straightened hand paths, which suggested better coordination of elbow-shoulder
      motion, and improved on the RMA. High-level subjects decreased trunk use at
      ipsilateral target after PRE, which was not observed after TRT. No significant
      differences between training conditions were found for other kinematic variables.
      CONCLUSIONS: Training benefits appear to depend on initial level of functioning.
      Although compensatory trunk use was evident, low-level subjects seemed to benefit
      most from TRT. High-level subjects, whose kinematics showed fairly normal
      movement organization, demonstrated less compensatory movement after PRE.

PMID- 15468021
TI  - Dynamic analysis of trunk flexion after stroke.
AB  - OBJECTIVE: To quantify trunk movement and lower-extremity weight bearing in
      patients with stroke-associated hemiparesis compared with healthy subjects.
      DESIGN: Controlled study with 2 groups: persons with hemiparesis and healthy
      controls. SETTING: Geriatric center offering rehabilitation services.
      PARTICIPANTS: A convenience sample of 15 persons with poststroke hemiparesis
      (age, 69.4+/-12.0y; > or =3mo poststroke; total motor function range, 63-95/100)
      on the Fugl-Meyer Assessment and of 13 healthy persons (age, 67.8+/-7.5y).
      INTERVENTIONS: Subjects were seated on a chair placed on a forceplate with their
      feet on 2 additional forceplates. A target was placed directly in front of or at
      a 45 degrees angle from the midline at 66% of the nonparetic/dominant arm length.
      Subjects' task was to touch the target with their forehead. Main outcome measures
      Amplitude and speed of trunk movements, displacement of the global center of
      pressure (COP), and percentage of body weight distributed on the buttocks and the
      feet. RESULTS: Despite speed and amplitude comparable to that of the healthy
      subjects (NS), subjects with hemiparesis (HS) had less COP displacement (HS,
      33.7+/-6.9; NS, 40.5+/-9.2), resulting in a lower weight-bearing value on the
      feet (HS for the paretic foot, 2.3%+/-3.6%; HS for the nonparetic foot, 2.2%+/
      2.9%; NS for the nondominant foot, 5.4%+/-3.4%; NS for the dominant foot, 5.2%+/
      4.0%). CONCLUSIONS: The similar amplitude of trunk flexion with a decreased
      displacement of COP and a lower weight bearing on the feet suggest smaller
      anterior displacement of the body mass. It is possible that trunk movements in
      persons with hemiparesis are executed by the upper trunk with very little
      anterior tilt of the pelvis.

PMID- 15468022
TI  - Foot contact pattern analysis in hemiplegic stroke patients: an implication for
      neurologic status determination.
AB  - OBJECTIVE: To investigate the feasibility of using a foot contact pattern to
      predict neurologic recovery and the effect of ambulation training in hemiplegic
      stroke patients. DESIGN: Case-comparison study. SETTING: Gait laboratory in a
      tertiary care center. PARTICIPANTS: Sixty-five functionally ambulant hemiplegic
      stroke patients, and 30 healthy subjects serving as the control group.
      INTERVENTIONS: Gait analyses were performed by using the conventional gait
      analysis system (6 cameras) and the portable Computer DynoGraphy (CDG) system.
      Main outcome measures Walking velocity, step length, and cadence were measured
      from the conventional gait analysis system. Cyclogram, gaitline, and ground
      reaction force (GRF) patterns were recorded with the CDG system. RESULTS:
      Velocity, cadence, and step length increased in higher Brunnstrom stages (P<.01).
      Negative correlation was noted between the Brunnstrom stages and the foot contact
      patterns (P<.01). Lower cyclogram, GRF, and gaitline patterns were expected in
      subjects with higher Brunnstrom stages. There were high prediction probabilities
      between cyclogram, gaitline, and GRF patterns. CONCLUSIONS: Foot contact pattern
      can be a simple and reliable indicator of hemiplegic gait in stroke patients. It
      is closely related to patient's neurologic status and is correlated with
      parameters obtained from conventional gait analysis systems. Pathologic
      presentations are noted in both the affected and unaffected limbs, suggesting
      that rehabilitation programs should be implemented on both sides.

PMID- 15468023
TI  - Ankle stiffness and tissue compliance in stroke survivors: a validation of
      Myotonometer measurements.
AB  - OBJECTIVE: To determine the construct validity of Myotonometer measurements of
      tissue compliance as being reflective of ankle plantarflexor tone. DESIGN: Cross
      sectional. SETTING: Motor performance research laboratory. PARTICIPANTS: Twenty
      three stroke survivors (67.5+/-10.9y) and 24 control subjects (71.2+/-9.0y)
      recruited from the community. INTERVENTIONS: Not applicable. Main outcome
      measures Plantarflexor tone was measured using the Modified Ashworth Scale (MAS),
      ankle stiffness (total, passive, intrinsic and reflex components) was quantified
      using a torque motor, and tissue compliance during relaxation and activation of
      the plantarflexors was measured with the Myotonometer. RESULTS: MAS scores in the
      stroke group ranged from 1 to 4, whereas all control subjects had normal tone.
      Mean total ankle stiffness was higher in the stroke group than in the control
      group (P<.02), mainly due to elevated passive stiffness (P<.03). Compliance did
      not change as a function of muscle activation in stroke, but it decreased when
      control subjects contracted their plantarflexors (P<.04). The difference in
      Myotonometer measurements acquired during active and relaxed states was
      associated with total ankle stiffness and, specifically, intrinsic stiffness. The
      relationships were strongest when only stroke data were considered. CONCLUSIONS:
      Stiffness and compliance measures distinguished between control subjects and
      persons with hypertonia secondary to stroke. Compliance differences in the
      relaxed and active gastrocnemius muscle reflected intrinsic stiffness associated
      with the contractile elements of the plantarflexor group of muscles as a whole.

PMID- 15468024
TI  - Biomechanic changes in passive properties of hemiplegic ankles with spastic
      hypertonia.
AB  - OBJECTIVE: To investigate quantitatively biomechanic changes in the passive
      properties of hemiplegic spastic ankles. DESIGN: Evaluation of spastic hypertonia
      by moving the ankle joint slowly between dorsiflexion and plantarflexion extreme
      positions under controlled joint torque and position. SETTING: Institutional
      research center. PARTICIPANTS: Twenty-four stroke patients with spastic ankles
      and 32 healthy controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Passive resistance torque at controlled dorsiflexion and plantarflexion
      positions, dorsiflexion and plantarflexion range of motion (ROM) at controlled
      torques, and quasistatic stiffness and energy loss in dorsiflexion and
      plantarflexion. RESULTS: Spastic hypertonic ankles showed significant alterations
      of the passive properties in plantarflexion (P=.041) as well as in dorsiflexion
      (P=.016) directions. Compared with healthy controls, spastic ankles showed higher
      resistance torque (9.51+/-4.79Nm vs 6.21+/-3.64Nm, P=.016), higher quasistatic
      stiffness (.54+/-.19Nm/deg vs .35+/-.20Nm/deg, P=.001) at 10 degrees of
      dorsiflexion, larger normalized dorsiflexion energy loss (.068+/-.04J/deg vs
      .04+/-.02J/deg, P=.037), and decreased dorsiflexion ROM at 10Nm of resistance
      torque (10.77 degrees +/-8.69 degrees vs 20.02 degrees +/-11.67 degrees ,
      P=.014). The resistance torque, ROM, and stiffness of spastic hypertonic ankles
      in plantarflexion showed similar changes (P<.05) to those in dorsiflexion. The
      passive ROM, joint stiffness, and resistance torque at controlled positions
      correlated with each other and also correlated with the Modified Ashworth Scale
      (P<.01). CONCLUSIONS: Various biomechanic changes in both plantar- and
      dorsiflexors are associated with spastic hypertonia of chronic stroke patients,
      and they can be evaluated quantitatively under well-controlled conditions. With
      simplifications, the various measures in this study can potentially be used to
      obtain more comprehensive and quantitative evaluations of spastic hypertonia in a
      clinical setting.

PMID- 15468025
TI  - Impairment and activity limitation associated with epiphyseal dysplasia in
      children.
AB  - OBJECTIVES: To develop a profile of impairment and activity limitation among
      children with epiphyseal dysplasia (ED) and to identify the relationship between
      these 2 domains. DESIGN: Cross-sectional study. SETTING: Acute, pediatric
      academic and health sciences center. PARTICIPANTS: Eleven subjects with multiple
      epiphyseal dysplasia (MED) and 17 subjects with spondyloepiphyseal dysplasia
      (SED), with a mean age of 12.9 years. INTERVENTIONS: Not applicable. Main outcome
      measures Anthropometric indexes of growth and nutrition, joint range of motion
      (ROM) and alignment, muscle strength, pain, and activity limitation. RESULTS:
      Subjects with SED had significantly shorter stature than the reference population
      (P<.01). Seventy-three percent of participants with MED and 77% of those with SED
      were above average or overweight for their height (P<.01). Both groups presented
      with moderate to severe joint ROM impairment, with greater lower-extremity
      involvement. Subjects with SED had worse outcomes with respect to overall ROM and
      alignment impairments (P<.01), particularly in their upper extremities (P<.01),
      than subjects with MED. Significant overall muscle weakness was noted in all
      subjects (z=-1.81; P<.01). Ninety-four percent of subjects with SED reported pain
      with activity, compared with 64% of those with MED (P=.04), although pain
      intensity did not differ between groups. Fifty percent of subjects had undergone
      orthopedic surgery. Mild activity limitation was reported by all subjects (mean
      score, 87.7+/-18.83). Significant correlations were identified between height for
      age and strength (r=.50) and pain and activity limitation (r=-.50). CONCLUSIONS:
      Despite moderate to severe impairments, all subjects reported surprisingly mild
      activity limitation. A positive correlation was identified between pain and
      activity limitation. This study also identified and described patterns of muscle
      weakness, pain, and nutritional concerns not previously reported in the ED
      literature.

PMID- 15468026
TI  - Therapeutic ultrasound and fracture healing: a survey of beliefs and practices.
AB  - OBJECTIVE: To explore current beliefs among senior physiotherapy (PT) students
      and orthopedic surgeons on the clinical utility of therapeutic ultrasound for
      assisting fracture healing. DESIGN: Cross-sectional survey. SETTING: University.
      PARTICIPANTS: Orthopedic surgeons, senior orthopedic surgery residents, and PT
      students in their final 6 months of study. INTERVENTIONS: Not applicable. Main
      outcome measures Percentage of respondents reporting specific perceptions on (1)
      the role of therapeutic ultrasound in fracture healing, (2) clinical use of
      therapeutic ultrasound for fracture healing, (3) rationale for not using
      therapeutic ultrasound for healing fractures, and (4) what constitutes a
      clinically significant difference in fracture healing time. Between-group
      comparisons were conducted for survey responses. RESULTS: The response rate was
      20 of 22 (90.9%) orthopedic surgeons, 5 of 5 (100%) senior orthopedic residents,
      and 34 of 50 (68.0%) senior PT students. The majority of senior PT students
      (58.8%) and orthopedic residents and surgeons (60.0%) surveyed reported the
      belief that therapeutic ultrasound may help in assisting fracture healing in some
      cases. However, the majority of respondents do not use this modality (60.0% of
      surgeons, 88.2% of Senior PT students), with most surgeons (32.0%) citing lack of
      evidence and most senior PT students (58.8%) indicating lack of availability as
      the predominant barrier. Thirty-two percent of surgeons felt that ultrasound was
      contraindicated and harmful to healing fractures, or that it was of no use, and
      20.5% of PT students reported the belief that ultrasound was contraindicated and
      was, or may be, harmful to healing bone. Most orthopedic residents and surgeons
      (52.0%) reported that a reduction in fracture healing time of 4 weeks would be
      clinically significant versus senior PT students, the majority of whom (64.7%)
      indicated that a reduction of 2 weeks would be clinically significant.
      CONCLUSIONS: Some surgeons and PT students believed that therapeutic ultrasound
      is contraindicated and harmful to healing bone; however, most believed that
      therapeutic ultrasound may help in assisting fracture healing, in at least some
      cases. Current usage of this modality is rare, primarily due to the perceived
      lack of evidence and lack of availability. Large randomized trials are needed to
      define further the role of ultrasound in fracture healing.

PMID- 15468027
TI  - Efficacy of multiwavelength light therapy in the treatment of pressure ulcers in
      subjects with disorders of the spinal cord: A randomized double-blind controlled
      trial.
AB  - OBJECTIVE: To study the efficacy of multiwavelength light therapy in the
      treatment of pressure ulcers in subjects with spinal cord disorders. DESIGN:
      Randomized controlled trial. SETTING: Neurologic rehabilitation ward of a
      referral center in India. PARTICIPANTS: Thirty-five subjects with spinal cord
      injury, with 64 pressure ulcers (stage 2, n=55; stage 3, n=8; stage 4, n=1), were
      randomized into treatment and control groups. One subject refused consent. Mean
      duration of ulcers in the treatment group was 34.2+/-45.5 days and in the control
      group, 57.1+/-43.5 days. INTERVENTIONS: Treatment group received 14 sessions of
      multiwavelength light therapy, with 46 probes of different wavelengths from a
      gallium-aluminum-arsenide laser source, 3 times a week. Energy used was 4.5
      J/cm(2). Ulcers in the control group received sham treatment. MAIN OUTCOME
      MEASURES: Healing of the ulcer, defined as the complete closure of the wound with
      healthy scar tissue, time taken for the ulcer to heal, and stage of the ulcer and
      Pressure Sore Status Tool score 14 days after last treatment. RESULTS: There was
      no significant difference in healing between the treatment and control groups.
      Eighteen ulcers in treatment group and 14 in control group healed completely ( P
      =.802). Mean time taken by the ulcers to heal was 2.45+/-2.06 weeks in the
      treatment group and 1.78+/-2.13 weeks in the control group ( P =.330). Time taken
      for stage 3 and 4 ulcers to reach stage 2 was 2.25+/-0.5 weeks in treatment group
      and 4.33+/-1.53 weeks in control group ( P =.047). CONCLUSIONS: Multiwavelength
      light therapy from a gallium-aluminum-arsenide laser source did not influence
      overall healing pressure ulcers. Limited evidence suggested that it improved
      healing of stage 3 and 4 pressure ulcers.

PMID- 15468028
TI  - Outcome after mild to moderate traumatic brain injury: the role of dizziness.
AB  - OBJECTIVE: To assess the specific effect of dizziness on psychosocial outcome
      after mild to moderate traumatic brain injury (TBI). DESIGN: Six-month cross
      sectional study. Setting An outpatient TBI clinic in a tertiary care referral
      center. Participants A consecutive sample of 207 adults with mild to moderate
      TBI, 138 (66.7%) of whom had subjective complaint of posttraumatic dizziness.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Psychosocial indices
      (Glasgow Outcome Scale [GOS], General Health Questionnaire [GHQ], Rivermead Head
      Injury Follow-Up Questionnaire [RHFUQ], return to work status) were collected
      from dizzy and nondizzy patients. RESULTS: Despite similar demographic, TBI, and
      global disability (GOS) profiles of both groups, psychosocial functioning (GHQ,
      RHFUQ, return to work) was significantly worse in dizzy subjects ( P <.01 for all
      indices). A logistic regression analysis identified dizziness ( P =.006), total
      GHQ ( P =.001), and psychotropic and analgesic use ( P =.05) as significant
      independent predictors of reemployment. CONCLUSIONS: Although dizziness was
      closely linked to psychologic distress at 6 months after head injury, it also
      emerged as an independent predictor of failure to return to work, suggesting that
      not all its adverse effects on outcome are psychologically mediated. Clinicians
      need to be alert to the presence of dizziness as an adverse prognostic indicator
      after mild to moderate TBI.

PMID- 15468029
TI  - Oculomotor rehabilitation in acquired brain injury: a case series.
AB  - OBJECTIVE: To investigate the effects of systematic, oculomotor rehabilitation on
      basic versional ocular motility, as well as reading eye movements, in subjects
      with acquired brain injury, using objective eye movement recording and subjective
      rating of reading ability. DESIGN: Case series. SETTING: Clinical research
      laboratory. PARTICIPANTS: Two men with acquired brain injury: one with traumatic
      brain injury and one with stroke. INTERVENTIONS: Versional oculomotor training
      was performed for 1 hour, twice weekly for 8 weeks. There were 2 feedback modes
      of training: normal internal oculomotor visual feedback alone (4wk), or that
      feedback in conjunction with external oculomotor auditory feedback (4wk). Testing
      was conducted before and after training. Main outcome measures Objective outcome
      measures included both basic eye movement parameters (fixational accuracy,
      saccadic gain and latency, pursuit gain, mean saccade frequency ratio for
      simulated reading), and reading eye movement parameters (words per minute, grade
      level equivalent, fixations per 100 words, regressions per 100 words, percentage
      of reading comprehension, duration of fixation in seconds). Subjective outcome
      measures included the subject's ability to read based on the responses to the
      reading rating-scale questionnaire. RESULTS: Both subjects improved objectively
      in terms of basic versional oculomotor accuracy and reading ability. These
      findings concurred with their subjective impressions. CONCLUSIONS: This case
      series provides objective documentation of the positive effects of oculomotor
      rehabilitation on basic ocular motility and reading ability in selected cases
      with acquired brain injury, thus suggesting the need for a larger clinical trial
      in this area.

PMID- 15468031
TI  - Decreased neck muscle strength is highly associated with pain in cervical
      dystonia patients treated with botulinum toxin injections.
AB  - OBJECTIVES: To compare the isometric neck muscle strength of cervical dystonia
      patients treated with botulinum toxin injections with that of healthy control
      subjects and to evaluate the association between neck strength, neck pain, and
      disability in these patients. DESIGN: Clinical cross-sectional study. SETTING:
      Outpatient rehabilitation and neurology clinics in a Finnish hospital.
      PARTICIPANTS: Twenty-three patients with cervical dystonia with botulinum toxin
      treated neck muscles and 23 healthy control subjects. INTERVENTIONS: Not
      applicable. Main outcome measures Isometric neck strength was measured by a
      special neck strength measurement system. Disability was measured by the Neck
      Disability Index, and pain and symptoms of cervical dystonia by a visual analog
      scale. RESULTS: Isometric neck strength in all directions measured was
      significantly lower (25%-44%) in the cervical dystonia patients than in the
      healthy controls. Neck pain levels reported during the strength tests (r range, 
      .36 to -.70) and neck pain experienced during the preceding week (r range, -.52
      to -.63) were inversely associated with isometric strength results. The
      difference between sides in rotation strength was 35% in the patient group
      (P<.001), whereas no significant difference between sides was found in the
      healthy controls. Fifty-one percent of the patients reported moderate or severe
      disability. Pain, stiffness, and incorrect position of the head were the most
      prominent symptoms. CONCLUSIONS: Cervical dystonia patients with botulinum toxin
      treated neck muscles showed significantly lower maximal neck strength than
      healthy controls. The patients also had a statistically significant difference
      between sides in neck rotation strength. Thus, strength measures may be useful to
      detect disturbance in the function of the neck muscles.

PMID- 15468030
TI  - Musculoskeletal pain in polio survivors and strength-matched controls.
AB  - OBJECTIVES: To determine whether a significant difference exists between
      musculoskeletal symptoms of polio survivors and those of older adults with no
      history of polio, and to determine if activity level and strength predict pain in
      either group. DESIGN: Matched research design. SETTING: A research laboratory in
      a rehabilitation setting. PARTICIPANTS: Fifty-four polio survivors and 54 adults
      with no history of polio were matched for gender, race, and bilateral knee
      extensor strength and selected from a cohort of 316 subjects who participated in
      a study on the relation between activity level and health status. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Location and severity of musculoskeletal
      pain, activity frequency and intensity level, maximum voluntary isometric
      strength, and physical performance measures. RESULTS: Polio survivors reported
      significantly more symptoms than the matched controls ( P <.05). Symptom status
      among the polio survivors was strongly associated with performance strain,
      perceived exertion, and activity intensity. Although the polio survivors had
      activity frequencies and habitual walking speeds that were similar to those from
      the matched controls, there was evidence that they performed activities at higher
      intensity levels. CONCLUSIONS: Activity level is a factor in the development of
      musculoskeletal symptoms in polio survivors. Polio survivors who perform at
      higher intensity levels are more likely to have moderate to severe pain and more
      mobility difficulties.

PMID- 15468032
TI  - Joint range of motion limitations in children and young adults with spinal
      muscular atrophy.
AB  - OBJECTIVES: To elicit descriptive data about limited joint range of motion (ROM)
      in subjects with type II or III spinal muscular atrophy (SMA) and to examine the
      relation between the number of motions with limited range and both age and
      functional ability. DESIGN: Descriptive cross-sectional study. SETTING:
      Neurologic pediatric outpatient clinic at a hospital in Taiwan. PARTICIPANTS:
      Twenty-seven subjects with SMA type II (mean age, 9.8+/-6.5y) and 17 with SMA
      type III (mean age, 12.2+/-8.7y). Intervention Measurement with transparent
      goniometers of joint ROM bilaterally of the shoulder, elbow, wrist, hip, knee,
      and ankle. MAIN OUTCOME MEASURES: The proportion of participants with each ROM
      limitation compared with all participants with the same SMA type, age
      distribution of the participants with each ROM limitation, mean range loss of
      each motion limitation, and the contracture index (risk index of joint
      contracture). RESULTS: Eighty-nine percent of the participants with SMA type II
      experienced knee extension limitation. Approximately 50% of the participants with
      both types of SMA had ankle dorsiflexion limitation. The motions of knee and hip
      extension and ankle dorsiflexion also had a relatively high contracture index.
      The number of motions with limited range positively correlated ( P <.001) with
      age and upper-extremity functional grade (the higher the functional grade, the
      poorer the functional ability) for SMA type II. CONCLUSIONS: We found varying
      degrees of joint ROM limitation. Certain motions were noted to be high risks for
      the development of contractures. This risk was higher mostly in younger children.

PMID- 15468034
TI  - Twenty-seven years of complication-free life with clean intermittent self
      catheterization in a patient with spinal cord injury: A case report.
AB  - Currently, clean intermittent self-catheterization (CISC) is the most prevalent
      method of bladder management in patients with spinal cord injury (SCI) at
      discharge from rehabilitation centers. However, half of the patients discontinue
      using CISC and change to other methods of bladder management several months
      postdischarge despite the fact that it the best way to prevent urinary tract
      complications. Few studies, however, report the long-term consequences of CISC.
      In this case, we present a woman in her early fifties who had sustained thoracic
      SCI and had continued using CISC for 27 years without developing any
      complications. The possible reasons for her success were absence of incontinence
      because of underactive and normal capacity bladder; normal upper-extremity
      functions and absence of marked spasticity of lower extremities that facilitated
      CISC technique; and absence of sociovocational problems, enabling her to keep
      proper intervals between catheterizations each day. This case indicates that CISC
      is useful for long-term bladder management in patients with SCI, even for 25
      years or more. Long-term outcomes of CISC and factors leading to success need to
      be delineated in future studies with larger samples.

PMID- 15468033
TI  - The effects of exercise training on elderly persons with cognitive impairment and
      dementia: a meta-analysis.
AB  - OBJECTIVE: To determine by meta-analysis whether physical exercises are
      beneficial for people with dementia and related cognitive impairments. DATA
      SOURCES: Published articles and nonpublished manuscripts from 1970 to 2003 were
      identified by using electronic and manual searches. Key search words included
      exercise, rehabilitation, activities of daily living, dementia, Alzheimer's
      disease, aged, and geriatrics. STUDY SELECTION: Reviewed studies were limited to
      randomized trials evaluating exercise in persons 65 years of age or older with
      cognitive impairment. Studies included quantitative results (means, standard
      deviations, t tests, F tests) for physical fitness, physical functioning,
      cognition, or behavior outcomes. DATA EXTRACTION: One reviewer extracted data on
      study characteristics and findings. Selected articles were evaluated for
      methodologic quality by 2 raters. DATA SYNTHESIS: A total of 2020 subjects
      participated in the 30 trials that met the inclusion criteria. Summary effects
      were computed using a fixed effects (Hedge's g(i)) model. Significant summary
      effect sizes (ES) were found for strength (ES=.75; 95% confidence interval [CI],
      .58-.92), physical fitness (ES=.69; 95% CI, .58-.80), functional performance
      (ES=.59; 95% CI, .43-.76), cognitive performance (ES=.57; 95% CI, 0.43-1.17), and
      behavior (ES=.54; 95% CI, .36-.72). The overall mean ES between exercise and
      nonexercise groups for all outcomes was .62 (95% CI, .55-.70). CONCLUSIONS:
      Exercise training increases fitness, physical function, cognitive function, and
      positive behavior in people with dementia and related cognitive impairments.

PMID- 15468035
TI  - Distribution and extent of involvement in brachial plexopathies caused by gunshot
      wounds, motor vehicle crashes, and other etiologies: a 10-year electromyography
      study.
AB  - OBJECTIVE: To examine the differences in the extent and distribution of brachial
      plexopathy involvement caused by gunshot wounds (GSW), motor vehicle crashes
      (MVCs), and other etiologies, based on electrophysiologic data. DESIGN:
      Retrospective review of electrophysiologic data from 1993 to 2002. SETTING: A
      large urban county hospital. PARTICIPANTS: Sequential patients (N=109) with the
      diagnosis of brachial plexopathy established by electromyography testing. This
      included 35 patients with GSW, 25 involved in an MVC, and 49 with other
      etiologies. INTERVENTIONS: Not applicable. Main Outcome Measures The brachial
      plexus was divided into 9 regions: upper, middle, and lower root; upper, middle,
      and lower trunks; and lateral, posterior, and medial cords. Regions involved by
      needle study on electromyography were denoted as positive or negative. The total
      number of regions involved was also recorded. RESULTS: Injury was most common in
      the trunks (52%), cords (36%), and roots (12%) (Pearson chi(2), P<.000).
      Specifically, the "other" category had the greatest number of injuries to the
      trunks (54%) (Pearson chi(2), P<.000), whereas the trunks (46%) and cords (45%)
      were more evenly affected in GSW cases (Pearson chi(2), P=.585). In the MVC
      group, there was a trend toward more trunks (56%) being affected (Pearson chi(2),
      P=.076). CONCLUSIONS: Differences were noted in the distribution of injury when
      examining subtypes of traumatic brachial plexopathies.

PMID- 15468036
TI  - Energy expenditure and gait characteristics of a bilateral amputee walking with C
      leg prostheses compared with stubby and conventional articulating prostheses.
AB  - OBJECTIVE: To compare energy cost and stride characteristics during walking with
      3 different types of prostheses in a person with bilateral knee disarticulations.
      DESIGN: Single-case study. Setting Pathokinesiology laboratory. PARTICIPANT: A
      subject with bilateral knee disarticulations and bilateral transradial
      amputations secondary to meningococcemia with purpura fulminans. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Energy cost, stride characteristics, and
      motion analysis. RESULTS: When wearing the C-Leg prostheses, the subject walked
      the farthest and fastest, with an overall lower rate of oxygen consumption and
      oxygen cost compared with walking with either of the other prostheses. Gait
      analysis while the patient was wearing the C-Leg prostheses revealed premature
      hip extension, absence of knee flexion during loading response, and a rate of
      swing in the referent range. CONCLUSIONS: Walking in a C-leg was the most
      efficient method of ambulation for our subject.

PMID- 15468037
TI  - Effects of a simple functional electric system and/or a hinged ankle-foot
      orthosis on walking in persons with incomplete spinal cord injury.
AB  - OBJECTIVES: To compare the effect of functional electric stimulation (FES) with
      that of a hinged ankle-foot orthosis (AFO) for assisting foot clearance, gait
      speed, and endurance and to determine whether there is added benefit in using FES
      in conjunction with the hinged AFO in persons with incomplete spinal cord injury
      (SCI). DESIGN: Within-subject comparison of walking under 4 conditions: AFO, FES,
      AFO and FES, and no orthosis. A plastic hinged AFO was used for all AFO
      conditions. SETTING: Tertiary rehabilitation center. PARTICIPANTS: Nineteen
      subjects with incomplete SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: The self-selected gait speed, 6-minute walk distance, and foot
      clearance values were compared between conditions. RESULTS: Gait speed increased
      with FES ( P <.05) and with the AFO ( P =.06). Six-minute walk distance also
      increased with the AFO ( P <.05). No difference was found between the 2 forms of
      orthoses in either gait speed or endurance. The greatest increase in gait speed
      and endurance from the no-orthosis condition occurred with the combined AFO and
      FES condition. Foot clearance improved with FES but not with AFO. Subjects whose
      gait speed increased with FES had weaker hip flexors, knee flexors, and ankle
      dorsiflexors than those who did not benefit from FES. CONCLUSIONS: Both FES and
      the hinged AFO promote walking and FES is only superior to the AFO in increasing
      foot-clearance values. The hinged AFO and FES together may offer advantages over
      either device alone.

PMID- 15468038
TI  - A real-time plantar pressure feedback device for foot unloading.
AB  - OBJECTIVE: To develop and test a plantar pressure control device that provides
      both visual and auditory feedback and is suitable for correcting plantar pressure
      distribution patterns in persons susceptible to neuropathic foot ulceration.
      DESIGN: Pilot test. SETTING: Sports medicine laboratory in a university in
      France. PARTICIPANT: One healthy man in his mid thirties. INTERVENTIONS: Not
      applicable. Main outcome measures A device was developed based on real-time
      feedback, incorporating an acoustic alarm and visual signals, adjusted to a
      specific pressure load. Plantar pressure measured during walking, at 6 sensor
      locations over 27 steps under 2 different conditions: (1) natural and (2)
      unloaded in response to device feedback. RESULTS: The subject was able to modify
      his gait in response to the auditory and visual signals. He did not compensate
      for the decrease of peak pressure under the first metarsal by increasing the
      duration of the load shift under this area. Gait pattern modification centered on
      a mediolateral load shift. CONCLUSIONS: The auditory signal provided a warning
      system alerting the user to potentially harmful plantar pressures. The visual
      signal warned of the degree of pressure. People who have lost nociceptive
      perception, as in cases of diabetic neuropathy, may be able to change their
      walking pattern in response to the feedback provided by this device. The visual
      may have diagnostic value in determining plantar pressures in such patients. This
      pilot test indicates that further studies are warranted.

PMID- 15468039
TI  - Using the number needed to treat in clinical practice.
AB  - The number needed to treat (NNT) is gaining attention as a method of reporting
      the results of clinical trails with dichotomous outcome measures. The NNT is
      defined as the number of patients who would need to be treated, on average, with
      a specific intervention to prevent 1 additional bad outcome or to achieve 1
      desirable outcome in a given time period. Because it reports outcomes in terms of
      patient numbers, it is extremely useful to clinicians for making decisions about
      the effort expended with a particular intervention to achieve a single positive
      outcome. This special communication describes the NNT statistic and its utility
      for choosing clinical interventions.

PMID- 15468040
TI  - Hyperbaric oxygen for traumatic brain injury.

PMID- 15468044
TI  - Introduction. Advances in Gaucher Disease: therapeutic goals and evaluation and
      monitoring guidelines.

PMID- 15468045
TI  - Therapeutic goals in the treatment of Gaucher disease.
AB  - Gaucher disease, the most common lysosomal storage disorder, is a heterogeneous
      multisystem condition. Patients with non-neuronopathic (type 1) Gaucher disease
      may suffer from hepatomegaly, splenomegaly, thrombocytopenia, bleeding
      tendencies, anemia, hypermetabolism, skeletal pathology, growth retardation,
      pulmonary disease, and decreased quality of life. Enzyme replacement therapy
      (ERT) with mannose-terminated glucocerebrosidase reverses or ameliorates many of
      the manifestations of type 1 Gaucher disease. However, the variable disease
      pattern and severity, and the uncertain manner of progression, render the
      decision to initiate ERT difficult. Thus, implementation of treatment and
      evaluation of the therapeutic response must be tailored to the individual
      patient. To obtain an evidence-based consensus on contemporary therapeutic goals,
      an international panel of physicians with extensive clinical experience in
      Gaucher disease met to review the extant literature on its treatment. The panel
      adopted an integrated system-based approach to arrive at a comprehensive guide to
      individualized management. Here we establish goals of treatment in Gaucher
      disease and propose a comprehensive schedule of monitoring of all relevant
      aspects to confirm the achievement, maintenance, and continuity of the
      therapeutic response.

PMID- 15468046
TI  - Gaucher disease type 1: revised recommendations on evaluations and monitoring for
      adult patients.
AB  - For patients with type 1 Gaucher disease, challenges to patient care posed by
      clinical heterogeneity, variable progression rates, and potential permanent
      disability that can result from untreated or suboptimally treated hematologic,
      skeletal, and visceral organ involvement dictate a need for comprehensive, serial
      monitoring. An updated consensus on minimum recommendations for effective
      monitoring of all adult patients with type 1 Gaucher disease has been developed
      by the International Collaborative Gaucher Group (ICGG) Registry coordinators.
      These recommendations provide a schedule for comprehensive and reproducible
      evaluation and monitoring of all clinically relevant aspects of this disease. The
      initial assessment should include confirmation of deficiency of beta
      glucocerebrosidase, genotyping, and a complete family medical history. Other
      assessments to be performed initially and at regular intervals include a complete
      physical examination, patient-reported quality of life using the SF-36 survey,
      and assessment of hematologic (hemoglobin and platelet count), visceral, and
      skeletal involvement, and biomarkers. Specific radiologic imaging techniques are
      recommended for evaluating visceral and skeletal pathology. All patients should
      undergo comprehensive regular assessment, the frequency of which depends on
      treatment status and whether therapeutic goals have been achieved. Additionally,
      reassessment should be performed whenever enzyme therapy dose is altered, or in
      case of significant clinical complication.

PMID- 15468048
TI  - Familial insensitivity to pain (HSAN V) and a mutation in the NGFB gene. A
      neurophysiological and pathological study.
AB  - We have studied a large Swedish family with a mutation in the nerve growth factor
      beta (NGFB) gene causing insensitivity to deep pain without anhidrosis
      (hereditary sensory and autonomic neuropathy, type V; HSAN V). Painfree joint
      destruction and fractures were common. Peripheral nerve conduction was normal,
      but temperature thresholds were increased. Sural nerve biopsies showed a moderate
      loss of A delta fibers and a severe reduction of C fibers. The three most
      severely affected cases were all born to consanguineous parents, and were
      homozygotes for the causal genetic mutation. Treatment of these patients is
      discussed.

PMID- 15468049
TI  - Expression of calbindin-D28K by yolk sac and chorioallantoic membranes of the
      corn snake, Elaphe guttata.
AB  - The yolk splanchnopleure and chorioallantoic membrane of oviparous reptiles
      transport calcium from the yolk and eggshell to the developing embryo. Among
      oviparous amniotes, the mechanism of calcium mobilization to embryos has been
      studied only in domestic fowl, in which the mechanism of calcium transport of the
      yolk splanchnopleure differs from the chorioallantoic membrane. Transport of
      calcium is facilitated by calbindin-D(28K) in endodermal cells of the yolk
      splanchnopleure of chickens but the chorioallantoic membrane does not express
      calbindin-D(28K). We used immunoblotting to assay for calbindin-D(28K) expression
      in yolk splanchnopleure and chorioallantoic membrane of the corn snake, Elaphe
      guttata, to test the hypothesis that the mechanism of calcium transport by
      extraembryonic membranes of snakes is similar to birds. High calbindin-D(28K)
      expression was detected in samples of yolk splanchnopleure and chorioallantoic
      membrane during late embryonic stages. We conclude that calbindin-D(28K) is
      expressed in these extraembryonic membranes to facilitate transport of calcium
      and that the mechanism of calcium transport of the chorioallantoic membrane of
      the corn snake differs from that of the chicken. Further, we conclude that
      calbindin-D(28K) expression is developmentally regulated and increases during
      later embryonic stages in the corn snake.

PMID- 15468050
TI  - 2000 Year-old ancient equids: an ancient-DNA lesson from pompeii remains.
AB  - Ancient DNA extracted from 2000 year-old equine bones was examined in order to
      amplify mitochondrial and nuclear DNA fragments. A specific equine satellite-type
      sequence representing 3.7%-11% of the entire equine genome, proved to be a
      suitable target to address the question of the presence of aDNA in ancient bones.
      The PCR strategy designed to investigate this specific target also allowed us to
      calculate the molecular weight of amplifiable DNA fragments. Sequencing of a 370
      bp DNA fragment of mitochondrial control region allowed the comparison of ancient
      DNA sequences with those of modern horses to assess their genetic relationship.
      The 16S rRNA mitochondrial gene was also examined to unravel the post-mortem base
      modification feature and to test the status of Pompeian equids taxon on the basis
      of a Mae III restriction site polymorphism.

PMID- 15468051
TI  - Immuno-cross reactivity of transglutaminase and cornification marker proteins in
      the epidermis of vertebrates suggests common processes of soft cornification
      across species.
AB  - In differentiating mammalian keratinocytes proteins are linked to the plasma
      membrane by epidermal transglutaminases through N-epsilon-(gamma-glutamyl)-lysine
      isopeptide bonds to form the cornified cell envelope. The presence of
      transglutaminases and their protein substrates in the epidermis of nonmammalian
      vertebrates is not known. The present study analyses the presence and
      localization of the above proteins in the epidermis using immuno-cross reactivity
      across different classes of amniotes. After immunoblotting, some protein bands
      appear labelled for loricrin, sciellin, and transglutaminase in most species.
      These proteins are scarce to absent in the epidermis of aquatic species (goldfish
      and newt) where a stratum corneum is absent or very thin. The molecular weight of
      transglutaminase immunoreactive bands generally varies between 40 to 62 kDa, with
      the most represented bands at 52-57 kDa in most species. The more intense
      loricrin- and sciellin-immunoreactive bands are seen at 50-55-62 kDa, but are
      weak or absent in aquatic vertebrates. Loricrine-like immunoreactivity is present
      in the epidermis where alpha-(soft)-keratinization occurs. Isopeptide bonds are
      mainly associated to bands in the range of 50-62 kDa. In vertebrates where hard
      keratin is expressed (the beta-keratin corneous layer of sauropsids and in
      feathers) or in hair cortex of mammals, no loricrin-like, transglutaminase-, and
      isopeptide-bond-immunoreactivities are seen. Immunoblotting however shows
      loricrin-, sciellin-, and trasnsglutaminase-positive bands in the corneous layers
      containing beta-keratin. Histologically, the epidermis of most amniotes shows
      variable transglutaminase immunoreactivity, but isopeptide-bond and sciellin
      immunoreactivities are weak or undetactable in most species. The limitations of
      immunohistochemical methods are discussed and compared with results from
      immunoblotting. In reptilian epidermis transglutaminase is mainly localized in
      0.15-0.3 microm dense granules or diffuse in transitional alpha-keratogenic
      cells. In beta-keratogenic cells few small dense granules show a weak
      immunolabeling. Transglutaminase is present in nuclei of terminal differentiating
      alpha- and beta-keratinocytes, as in those of mature inner and outer root sheath.
      The present study suggests that keratinization based on loricrin, sciellin and
      transglutaminase was probably present in the stratum corneoum of basic amniotes
      in the Carboniferous. These proteins were mainly maintained in alpha-keratogenic
      layers of amniotes but decreased in beta-keratogenic layers of sauropsids
      (reptiles and birds). The study suggests that similar proteins for the formation
      of the cornified cell envelope are present in alpha-keratinocytes across
      vertebrates but not in beta-keratinocytes.

PMID- 15468052
TI  - Influence of genetic polymorphisms on biomarkers of exposure and genotoxic
      effects in styrene-exposed workers.
AB  - A study on 44 workers exposed to styrene and 44 matched referents was performed
      in order to examine the influence of genetic polymorphisms in biotransformation
      and DNA repair enzymes on the levels of N-terminal hemoglobin adducts and
      genotoxicity biomarkers. Urinary mandelic acid concentration averaged 201.57 mg/g
      creatinine +/-148.32 in exposed workers, corresponding to a calculated average
      airborne styrene exposure of 9.5 ppm +/-9.6. Individuals with a high level of N
      terminal valine adducts had higher levels of DNA damage, as evaluated by the
      Comet assay (r = 0.29, P = 0.008). Frequencies of micronucleated mononucleated
      lymphocytes (MNMC) (0.71 +/- 0.88 vs 0.11 +/- 0.20, P<0.0001), micronucleated
      binucleated lymphocytes (MNBC) (3.93 +/- 2.75 vs 2.65 +/- 1.94, p = 0.02) and
      micronucleated nasal epithelial cells (0.52 +/- 0.49 vs 0.23 +/- 0.31, p = 0.04)
      differed significantly between the exposed and referent groups. In the whole
      group of 88 individuals, higher frequencies of MNMC were found in individuals
      possessing the XRCC3 Met(241) allele and those individuals with the XRCC1 Gln(
      (399) ) allele showed higher frequencies of MNMC and MNCB. In vitro DNA repair
      capacity, as measured by residual DNA strand breaks in peripheral blood
      leukocytes after a styrene oxide challenge, was also influenced by styrene
      exposure, with an apparent induction of early repair mechanisms associated with
      the intensity of recent exposure and a reduction of late (24 h) repair capacity
      that was associated with the duration of employment. After 1 h of repair, lower
      levels of residual DNA damage were found in individuals possessing GSTT1 (P =
      0.043). After 24 h of repair, lower residual DNA damage was found in individuals
      homozygous for XRCC1 Arg(194) (P = 0.013). Multivariate regression analysis
      indicated that the duration of exposure, smoking habits and polymorphisms of
      XRCC1 at codon 399 were important variables affecting the genotoxic responses.
      Our data suggest that DNA damage is formed in workers exposed to low
      concentrations of styrene, and that genotypes of metabolising and DNA-repair
      genes are important for the assessment of individual genotoxic risk to styrene.
      The in vitro DNA repair phenotype assay might be a valuable method to estimate
      the susceptibility of workers.

PMID- 15468053
TI  - Anal sphincter electromyography: editing of sampled motor unit action potentials.
AB  - During multi-motor unit action potential (MUAP) analysis of the tonically
      contracted external anal sphincter (EAS), a mild interference pattern often
      obscures the baseline, affecting the algorithm's ability to determine accurate
      boundaries of detected MUAPs. To assess the equivalence of methods of editing and
      selecting candidate MUAPs from the EAS, 17 nulliparous women underwent concentric
      needle electromyography (EMG) of the EAS using multi-MUAP software. The selected
      MUAPs either were accepted without question ("automated"), or a subset was
      deleted due to a noisy baseline ("manual-deletion") or manually marked ("manual
      mark"). A second examiner repeated the analysis. Each examiner found that the two
      editing methods were equivalent and yielded results that differed from those
      obtained by automated analysis of unedited data. However, there was a moderate
      difference in MUAP amplitude when the manual-deletion method was compared between
      the two examiners. Editing of selected EAS MUAPs during multi-MUAP analysis is
      required, and development of common protocols is essential to enable meaningful
      comparisons between similar studies.

PMID- 15468054
TI  - Potential chemoprotective effects of the coffee components kahweol and cafestol
      palmitates via modification of hepatic N-acetyltransferase and glutathione S
      transferase activities.
AB  - Coffee drinking has been associated with reduced incidence of colorectal cancer,
      possibly via chemoprotection/modification of the metabolism of dietary
      heterocyclic amine carcinogens such as 2-amino-1-methyl-6-phenylimidazo-[4,5
      b]pyridine (PhIP) by kahweol and cafestol palmitates (K/C), two components of
      unfiltered coffee. Using the PhIP-exposed male Fisher F344 rat as a model, K/C
      have been shown to reduce colonic PhIP-DNA adducts by > 50%. We have used the
      male F344 rat to investigate the effects of dietary K/C (0.02-0.2% as a 1:1
      mixture) on the metabolism of PhIP by N-acetyltransferase- (NAT),
      sulfotransferase- (SULT), and glutathione-dependent pathways. K/C decreased
      hepatic NAT-dependent PhIP activation by up to 80% in a dose-dependent manner.
      Conversely, hepatic glutathione S-transferase (GST) activity/expression
      increased, e.g., 3-4 fold toward 1-chloro-2,4-dinitrobenzene (total activity), up
      to 23-fold toward 4-vinylpyridine (rGSTP1), and approximately 7-fold for rGSTA2
      protein. These effects had fully developed after 5 days of the test diet and
      persisted for at least 5 days after withdrawal of K/C. Hepatic glutathione
      increased two- to threefold and this increase was more short-lived than other
      changes. K/C did not modify hepatic SULT activity or colon NAT and GST
      activities. Benzylisothiocyanate and black tea, which have also been shown to
      reduce the formation of PhIP-DNA adducts in this model, had little effect on
      hepatic NAT, SULT, GST, or GSH. In primary culture of rat hepatocytes, both
      kahweol and cafestol palmitates reduced NAT activity by 80%. In summary, the
      unique potential of K/C to convert rapid acetylators to a slow acetylator
      phenotype, accompanied by GST induction, might contribute to chemoprevention
      against cancers associated with heterocyclic amines.

PMID- 15468055
TI  - Distinct roles of CTLA-4 and TGF-beta in CD4+CD25+ regulatory T cell function.
AB  - Both CTLA-4 and TGF-beta have been implicated in suppression by CD4+CD25+
      regulatory T cells (Treg). In this study, the relationship between CTLA-4 and TGF
      beta in Treg function was examined. Blocking CTLA-4 on wild-type Treg abrogated
      their suppressive activity in vitro, whereas neutralizing TGF-beta had no effect,
      supporting a TGF-beta-independent role for CTLA-4 in Treg-mediated suppression in
      vitro. In CTLA-4-deficient mice, Treg development and homeostasis was normal.
      Moreover, Treg from CTLA-4-deficient mice exhibited uncompromised suppressive
      activity in vitro. These CTLA-4-deficient Treg expressed increased levels of the
      suppressive cytokines IL-10 and TGF-beta, and in vitro suppression mediated by
      CTLA-4(-/-) Treg was markedly reduced by neutralizing TGF-beta, suggesting that
      CTLA-4-deficient Treg develop a compensatory suppressive mechanism through CTLA-4
      independent production of TGF-beta. Together, these data suggest that CTLA-4
      regulates Treg function by two distinct mechanisms, one during functional
      development of Treg and the other during the effector phase, when the CTLA-4
      signaling pathway is required for suppression. These results help explain
      contradictions in the literature and support the existence of functionally
      distinct Treg.

PMID- 15468056
TI  - Selective maturation of dendritic cells by Nippostrongylus brasiliensis-secreted
      proteins drives Th2 immune responses.
AB  - Helminth infections at mucosal and tissue sites strongly polarize towards Th2
      immune responses, following pathways which have yet to be elucidated. We
      investigated whether dendritic cells (DC) exposed to gastrointestinal nematodes
      induce Th2 differentiation and, if so, whether this outcome reflects the absence
      of DC activation (the default hypothesis). We studied secreted proteins from the
      parasite Nippostrongylus brasiliensis, which induce Th2 development in vivo
      without live infection. Murine bone marrow-derived DC pulsed with N. brasiliensis
      excretory/secretory antigen (NES) can, on transfer to naive recipients, prime
      mice for Th2 responsiveness. Heat inactivation of NES abolishes both its ability
      to drive Th2 responses in vivo and its capacity to stimulate DC for Th2
      induction. NES, but not heat-inactivated NES, up-regulates DC maturation markers
      associated with Th2 promotion (CD86 and OX40L), with little change to CD80 and
      MHC class II. Moreover, DC exposed to NES readily produce IL-6 and IL-12p40, but
      not IL-12p70. LPS induced high IL-12p70 levels, except in DC that had been pre
      incubated with NES. These data contradict the default hypothesis, demonstrating
      that a helminth product (NES) actively matures DC, selectively up-regulating CD86
      and OX40L together with IL-6 production, while blocking IL-12p70 responsiveness
      in a manner consistent with Th2 generation in vivo.

PMID- 15468057
TI  - PTEN permits acute increases in D3-phosphoinositide levels following TCR
      stimulation but inhibits distal signaling events by reducing the basal activity
      of Akt.
AB  - Phosphoinositide 3-kinase (PI3K) is important in TCR signaling. PI3K generates
      phosphatidylinositol 3, 4, 5-trisphosphate (PI-3,4,5-P3), which regulates
      membrane localization and/or activity of multiple signaling proteins. PTEN
      (phosphatase and tensin homologue deleted on chromosome 10) opposes PI3K,
      reversing this reaction. Maintaining the balance between these two enzymes is
      important for normal T cell function. Here we use the PTEN-null Jurkat T cell
      line to address the role of PTEN in modulating proximal and distal TCR-signaling
      events. PTEN expression at levels that restored low basal Akt phosphorylation (an
      indicator of PI-3,4,5-P3 levels), but which were not themselves cytotoxic, had
      minimal effect on TCR-stimulated activation of phospholipase Cgamma1 and Ca2+
      flux, but reduced the duration of extracellular signal-regulated kinase (Erk)
      activation. Distal signaling events, including nuclear factor of activated T
      cells (NFAT) activation, CD69 expression and IL-2 production, were all inhibited
      by PTEN expression. Notably, PTEN did not block TCR-stimulated PI-3,4,5-P3
      accumulation. The effect of PTEN on distal TCR signaling events was strongly
      correlated with the loss of the constitutive Akt activation and glycogen synthase
      kinase-3 (GSK3) inhibition that is typical of Jurkat cells, and could be reversed
      by expression of activated Akt or pharmacologic inhibition of GSK3. These results
      suggest that PTEN acts in T cells primarily to control basal PI-3,4,5-P3 levels,
      rather than opposing PI3K acutely during TCR stimulation.

PMID- 15468058
TI  - A mouse model of human adaptive immune functions: HLA-A2.1-/HLA-DR1-transgenic H
      2 class I-/class II-knockout mice.
AB  - HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice were created and
      their immunological potential evaluated in response to hepatitis B DNA vaccine.
      Every single immunized mouse developed hepatitis B virus-specific antibodies, HLA
      DR1-restricted helper, and HLA-A2.1-restricted cytolytic T cell responses
      directed at the same immunodominant epitopes as those identified in naturally
      infected or vaccinated humans. These mice were specifically protected against a
      hepatitis B-recombinant vaccinia virus infection with a 10,000-fold or more
      reduction of the virus load at day 4 post-challenge. These mice represent a
      unique in vivo experimental model for human immune function studies without any
      interference with mouse MHC response which dwarfed the prediction of human
      responses. Furthermore, they enable the complete monitoring of immune adaptative
      responses for preclinical screening of candidate vaccines.

PMID- 15468059
TI  - Function of discoidin domain receptor I in HGF-induced branching tubulogenesis of
      MDCK cells in collagen gel.
AB  - Discoidin domain receptor I (DDR1) is a receptor tyrosine kinase (RTK) and serves
      as the receptor for collagen in addition to integrins. It has been well
      established that Madin-Darby canine kidney (MDCK) cells develop branching tubules
      in three-dimensional collagen gel in the presence of hepatocyte growth factor
      (HGF). MDCK cells normally express DDR1. However, the function of DDR1 in this in
      vitro model system has not been understood. We established stable-transfected
      MDCK cells harboring DDR1a, DDR1b, or dominant-negative (DN) DDR1 and cultured
      these transfectants in collagen gel with HGF (2 ng/ml) for the studies of
      branching tubule morphogenesis. Whether DDR1 played roles in cell growth,
      apoptosis, and migration was examined. We found that cells over-expressing DDR1a
      and DDR1b developed shorter tubules with fewer branches in collagen gel. In
      contrast, DN DDR1 over-expressed cells could not form tubule structure, but
      instead developed mostly cell aggregates with multiple long extended processes.
      Over-expression of DDR1a and 1b in MDCK cells resulted in reduction of cell
      growth when cells were cultured on collagen gel-coated dishes or collagen gel. On
      the other hand, DN DDR1 enhanced cell death on collagen gel, suggesting that DDR1
      is involved in maintenance of cell survival. Moreover, over-expression of DDR1a
      and DDR1b markedly reduced collagen-induced migration capability, whereas DN DDR1
      enhanced it, suggesting that DDR1a and 1b may serve as a negative regulator for
      alpha2beta1 integrin during migration on collagen substratum. These results
      indicate that DDR1 plays important role in regulation of HGF-induced branching
      tubulogenesis by modulating cell proliferation, survival, and cell migration.

PMID- 15468060
TI  - Iron specific growth inhibition of Burkitt's lymphoma cells in vitro, associated
      with a decrease in translocated c-myc expression.
AB  - The cellular proto-oncogene c-myc is an important transcription factor that plays
      a role in several cellular activities such as proliferation, differentiation, and
      apoptosis. It follows that regulation of c-myc expression is crucial for
      maintaining cell integrity. Amplification or translocation can convert this proto
      oncogene into an activated oncogene, thereby deregulating c-myc expression.
      Changes in the expression of c-myc leading to malignant cell growth and tumor
      progression can also be triggered by extrinsic factors. It has been reported that
      iron can increase cell proliferation, mainly by stimulating DNA synthesis as well
      as by enhancing c-myc expression. Here, we studied the effect of iron on cells in
      which c-myc expression is deregulated by either chromosomal translocation or gene
      amplification. When added to Burkitt's lymphoma cell lines, iron markedly
      inhibits cell proliferation. This effect is mediated by a cell cycle arrest in
      G2/M, followed by an important decrease in c-myc expression, whereas no effect
      could be observed in a cell line harboring amplified c-myc. Moreover, the down
      regulation of c-myc expression, which is independent from cell cycle blockade,
      leads to cell death by apoptosis. Collectively, our results suggest the existence
      of a novel iron-dependent cell cycle regulatory mechanism involving modulation of
      translocated c-myc gene expression.

PMID- 15468061
TI  - Gold(I)-catalyzed 5-endo-dig carbocyclization of acetylenic dicarbonyl compounds.

PMID- 15468063
TI  - Stacking and hydrogen bonding: DNA cooperativity at melting.
AB  - By taking into account base-base stacking interactions we improve the Generalized
      Model of Polypeptide Chain (GMPC). Based on a one-dimensional Potts-like model
      with many-particle interactions, the GMPC describes the helix-coil transition in
      both polypeptides and polynucleotides. In the framework of the GMPC we show that
      correctly introduced nearest-neighbor stacking interactions against the
      background of hydrogen bonding lead to increased stability (melting temperature)
      and, unexpectedly, to decreased cooperativity (maximal correlation length). The
      increase in stability is explained as due to an additional stabilizing
      interaction (stacking) and the surprising decrease in cooperativity is seen as a
      result of mixing of contributions of hydrogen bonding and stacking.

PMID- 15468062
TI  - Design, synthesis, and evaluation of peptides with estrogen-like activity.
AB  - Currently used antiestrogenic drugs against hormone-dependent breast cancer, and
      estrogenic drugs used in treatment of osteoporosis, are associated with risk
      factors. Therefore, there is a strong need to develop selective estrogen receptor
      modulators with better tissue selectivity. In a recent study (Peptides, 2002,
      Vol. 3, 573-580), we used a monoclonal antibody to estradiol (mAb-E2) to screen a
      phage-display peptide library. We identified a 15-mer peptide (peptide H5) that
      recognizes mAb-E2 (IC(50) 1 microM) and estrogen receptor (ER)alpha (IC(50) 500
      microM) but not ERbeta, and displays estrogen-like activity in vitro and in vivo.
      In this study, we designed and prepared peptides based on peptide H5, which
      possess improved estrogenic activity, by evaluating their binding to mAb-E2 and
      to ERs. Initially, we determined the minimal binding sequence of peptide H5
      capable of binding mAb-E2 and ER. Subsequently, systematic single-residue
      replacements of the minimal sequence, followed by multiple-residue replacements,
      yielded hexa- and heptapeptides with increased affinities to mAb-E2 and to ER.
      The most promising peptides, VSWFFE (EMP-1) and VSWFFED (EMP-2) (EMP: estrogen
      mimetic peptide), bind mAb-E2 with high affinity (IC(50) of 6 and 30 nM,
      respectively), recognize ERs with increased affinity (IC(50) of 100 microM for
      ERalpha, and 100-250 microM for ERbeta), and possess estrogenic activity in vivo.
      The short peptides described in this study may be used as potential lead
      compounds for developing new ER ligands.

PMID- 15468064
TI  - The strongest isolable acid.

PMID- 15468065
TI  - Protein conformational transitions coupled to binding in molecular recognition of
      unstructured proteins: hierarchy of structural loss from all-atom Monte Carlo
      simulations of p27Kip1 unfolding-unbinding and structural determinants of the
      binding mechanism.
AB  - Conformational transitions coupled to binding are studied for the p27(Kip1)
      protein which undergoes a functional disorder-to-order folding transition during
      tertiary complex formation with the phosphorylated cyclin A-cyclin-dependent
      kinase 2 (Cdk2) binary complex. Temperature-induced Monte Carlo simulations of
      p27(Kip1) unfolding-unbinding carried out from the crystal structure of the
      tertiary complex have revealed a systematic trend in the hierarchy of structural
      loss for p27(Kip1) and a considerable difference in mobility of p27(Kip1)
      secondary structure elements. The most persistent interactions of p27(Kip1) at
      the intermolecular interface during unfolding-unbinding simulations are formed by
      beta-hairpin and beta-strand that on average maintain their structural integrity
      considerably longer than other p27(Kip1) elements. We have found that the
      ensemble of unfolded p27(Kip1) conformations is characterized by transitions
      between mostly unbound, collapsed conformations and entropically favorable
      p27(Kip1) conformations, which are weakly bound to the cyclin A side of the
      binary complex. The results of this study are consistent with the experimental
      evidence pointing to this region of the intermolecular interface as a potential
      initiation docking site during binding reaction and may reconcile conflicting
      experimental hypotheses on the recognition of substrate recruitment motifs.

PMID- 15468066
TI  - Structural analysis of amyloid beta peptide fragment (25-35) in different
      microenvironments.
AB  - Amyloid beta (Abeta) peptides are one of the classes of amphiphilic molecules
      that on dissolution in aqueous solvents undergo interesting conformational
      transitions. These conformational changes are known to be associated with their
      neuronal toxicity. The mechanism of structural transition involved in the
      monomeric Abeta to toxic assemblage is yet to be understood at the molecular
      level. Early results indicate that oriented molecular crowding has a profound
      effect on their assemblage formation. In this work, we have studied how different
      microenvironments affect the conformational transitions of one of the active
      amyloid beta-peptide fragments (Abeta(25-35)). Spectroscopic techniques such as
      CD and Fourier transform infrared spectroscopy were used. It was observed that a
      stored peptide concentrates on dissolution in methanol adopts a minor alpha
      helical conformation along with unordered structures. On changing the methanol
      concentration in the solvated film form, the conformation switches to the
      antiparallel beta-sheet structure on the hydrophilic surface, whereas the peptide
      shows transition from a mixture of helix and unordered structure into
      predominantly a beta-sheet with minor contribution of helix structure on the
      hydrophobic surface. Our present investigations indicate that the conformations
      induced by the different surfaces dictate the gross conformational preference of
      the peptide concentrate.

PMID- 15468067
TI  - Imine-stabilized zinc trimethylsilylchalcogenolates: powerful reagents for the
      synthesis of II-II'-VI nanocluster materials.

PMID- 15468068
TI  - Role of PRIP-1, a novel Ins(1,4,5)P3 binding protein, in Ins(1,4,5)P3-mediated
      Ca2+ signaling.
AB  - PRIP-1 was isolated as a novel inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]
      binding protein with a domain organization similar to phospholipase C-delta1 (PLC
      delta1) but lacking the enzymatic activity. Further studies revealed that the
      pleckstrin homology (PH) domain of PRIP-1 is the region responsible for binding
      Ins(1,4,5)P3. In this study we aimed to clarify the role of PRIP-1 at the
      physiological concentration in Ins(1,4,5)P3-mediated Ca2+ signaling, as we had
      previously used COS-1 cells overexpressing PRIP-1 (Takeuchi et al., 2000, Biochem
      J 349:357-368). For this purpose we employed PRIP-1 knock out (PRIP-1-/-) mice
      generated previously (Kanematsu et al., 2002, EMBO J 21:1004-1011). The increase
      in free Ca2+ concentration in response to purinergic receptor stimulation was
      lower in primary cultured cortical neurons prepared from PRIP-1-/- mice than in
      those from wild type mice. The relative amounts of [3H]Ins(1,4,5)P3 measured in
      neurons labeled with [3H]inositol was also lower in cells from PRIP-1-/- mice. In
      contrast, PLC activities in brain cortex samples from PRIP-1-/- mice were not
      different from those in the wild type mice, indicating that the hydrolysis of
      Ins(1,4,5)P3 is enhanced in cells from PRIP-1-/- mice. In vitro analyses revealed
      that type1 inositol polyphosphate 5-phosphatase physically interacted with a PH
      domain of PRIP-1 (PRIP-1PH) and its enzyme activity was inhibited by PRIP-1PH.
      However, physical interaction with these two proteins did not appear to be the
      reason for the inhibition of enzyme activity, indicating that binding of
      Ins(1,4,5)P3 to the PH domain prevented its hydrolyzation. Together, these
      results indicate that PRIP-1 plays an important role in regulating the
      Ins(1,4,5)P3-mediated Ca2+ signaling by modulating type1 inositol polyphosphate 5
      phosphatase activity through binding to Ins(1,4,5)P3.

PMID- 15468069
TI  - TGF-beta-induced expression of tissue inhibitor of metalloproteinases-3 gene in
      chondrocytes is mediated by extracellular signal-regulated kinase pathway and Sp1
      transcription factor.
AB  - Transforming growth factor (TGF-beta1) is a potent inducer of chondrogenesis and
      stimulant of cartilage extracellular matrix (ECM) synthesis. Tissue inhibitor of
      metalloproteinases-3 (TIMP-3) is located in ECM and is the major inhibitor of
      matrix metalloproteinases (MMPs) and aggrecanase, the principal enzymes
      implicated in collagen and aggrecan degradation in arthritis. We investigated the
      role of extracellular-signal-regulated kinase (ERK)-mitogen-activated protein
      kinases (MAPK) and Sp1 transcription factor in TGF-beta-induced TIMP-3 gene in
      chondrocytes and chondrosarcoma cells. TGF-beta time-dependently induced a
      sustained phosphorylation of ERK-MAPKs in primary human or bovine chondrocytes.
      Inhibitors of this pathway, PD98059 and U0126, downregulated TGF-beta-induced
      expression of TIMP-3 RNA and protein. Since the ERKs can phosphorylate Sp1, and
      the promoter of human TIMP-3 gene contains four Sp1-binding sites, we
      investigated whether Sp1 is a downstream target of this pathway. Mithramycin and
      WP631, the agents that prevent binding of Sp1 to its consensus site,
      downregulated TGF-beta-inducible TIMP-3 expression. Indeed, mithramycin blocked
      TGF-beta-stimulated Sp1 binding activity. Transfection of cytomegalovirus (CMV)
      promoter-Sp1 plasmid increased TIMP-3 promoter (-940 to +376)-driven luciferase
      activity. Depletion of Sp1 by transfection of an antisense phosphorothioate
      oligonucleotide suppressed TGF-beta-induced TIMP-3 protein expression, while its
      sense homolog had no effect. These results suggest that activation of ERK-MAPK
      pathway and Sp1 transcription factor play a pivotal role in the induction of TIMP
      3 by TGF-beta in chondrocytes.

PMID- 15468071
TI  - Mass spectrometric analysis of tumor necrosis factor receptor-associated factor 1
      ubiquitination mediated by cellular inhibitor of apoptosis 2.
AB  - Signaling complexes formed on tumor necrosis factor receptor 2 (TNF-R2) contain
      adaptor proteins TNF-R-associated factors (TRAFs) 1 and 2, and cellular
      inhibitors of apoptosis (cIAPs) 1 and 2 which function as regulators of
      programmed cell death. TRAF2, cIAP1 and cIAP2 all have RING finger domains known
      to possess E3 ubiquitin ligase activity, implying that ubiquitination may play an
      important role in the TNF signaling pathway. In this report, we have shown that
      cIAP2 specifically mediated ubiquitination and proteasome-dependent degradation
      of TRAF1. To identify the sites for cIAP2-mediated ubiquitination of TRAF1, we
      used high pressure liquid chromatography coupled with tandem mass spectrometry.
      Lys185 and Lys193 of TRAF1 were found to be modified with ubiquitin chains.
      Mutation of Lys185 and Lys193 to Arg almost completely blocked cIAP2-mediated
      ubiquitination of TRAF1, indicating that they are the major, if not the only,
      sites of TRAF1 ubiquitination. Our data suggest that cIAP2 may regulate the
      turnover of TRAF1 by adding polyubiquitin chains on Lys185 or Lys193 following
      its recruitment to TNF-R signaling complexes.

PMID- 15468070
TI  - Preparation and synthetic applications of 2-halotryptophan methyl esters:
      synthesis of spirotryprostatin B.

PMID- 15468072
TI  - Neural tube defect rates before and after food fortification with folic acid.
AB  - BACKGROUND: Since 1998, enriched cereal grains sold in the United States have
      been fortified with folic acid, to reduce the incidence of neural tube defects
      (NTDs). The Centers for Disease Control and Prevention (CDC) recently reported
      that NTD rates have decreased 26% since fortification, but that additional effort
      is needed to achieve the national goal of a 50% reduction. However, accurate
      determination of NTD rates requires counting antenatally detected cases; the CDC
      study noted that the number of prenatally diagnosed cases was likely
      underestimated. METHODS AND RESULTS: We examined studies from the United States
      and Canada that compared rates of NTDs before and after very similar
      fortification programs were instituted in each country. U.S. studies had
      incomplete ascertainment of prenatally diagnosed NTD cases, and as a result,
      underreported the number of NTDs prevented. Canadian studies, in which
      ascertainment was more complete, showed decreases in NTD rates up to 54%.
      CONCLUSIONS: There is a strong correlation between the completeness of
      ascertainment and the percentage decrease in NTD rates. Studies that identify
      cases best show that folic acid fortification is preventing around 50% of NTDs.
      The percentage of NTDs that are folate-preventable in the United States is
      uncertain, but is probably 50-60%. Thus, we may be quite close to achieving the
      optimum level of protection at current fortification levels.

PMID- 15468073
TI  - The effect of fever, febrile illnesses, and heat exposures on the risk of neural
      tube defects in a Texas-Mexico border population.
AB  - BACKGROUND: Hyperthermia produces neural tube defects (NTDs) in a variety of
      animal species. Elevated maternal body temperatures may also place the developing
      human embryo at risk. We examined the relation between maternal hyperthermia and
      the development of NTDs in a high-risk Mexican-American population. METHODS: Case
      women were Mexican-American women with NTD-affected pregnancies who resided and
      delivered in any of the 14 Texas counties bordering Mexico, during 1995-2000.
      Control-women were randomly selected from study area residents delivering normal
      live births, frequency-matched to cases by hospital and year. Information on
      maternal fevers, febrile illnesses, exposures to heat generated from external
      sources, and hyperthermia-inducing activities was gathered through in-person
      interviews, conducted about six weeks postpartum. RESULTS: The risk effect (OR)
      associated with maternal fever in the first trimester, compared to no fever, was
      2.9 (95% CI, 1.5-5.7). Women taking fever-reducing medications showed a lower
      risk effect (OR, 2.4; 95% CI, 1.0-5.6) than those who did not (OR, 3.8; 95% CI,
      1.4-10.9). First-trimester maternal exposures to heat devices such as hot tubs,
      saunas, or electric blankets were associated with an OR of 3.6 (95% CI, 1.1
      15.9). Small insignificant effects were observed for activities such as cooking
      in a hot kitchen (OR, 1.6; 95% CI, 1.0-2.6) and working or exercising in the sun
      (OR, 1.4; 95% CI, 0.9-2.2). CONCLUSIONS: Maternal hyperthermia increases the risk
      for NTD-affected offspring. Women intending to become pregnant should avoid
      intense heat exposures, carefully monitor and manage their febrile illnesses, and
      routinely consume folic acid supplements.

PMID- 15468074
TI  - Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome.
AB  - We investigated coexisting autoantibodies in sera of 553 patients with a
      neurological presentation and one or more paraneoplastic neuronal nuclear or
      cytoplasmic autoantibodies: antineuronal nuclear autoantibody type 1 (ANNA-1),
      ANNA-2, ANNA-3; Purkinje cell cytoplasmic autoantibody type 1 (PCA-1), PCA-2; and
      CRMP-5-immunoglobulin G or amphiphysin-immunoglobulin G. Except for PCA-1, which
      occurred alone, 31% of sera had more than one of these autoantibodies. In
      addition, 25% of sera had neuronal calcium channel (P/Q-type or N-type),
      potassium channel, ganglionic acetylcholine receptor, muscle acetylcholine
      receptor, or striational antibodies. The autoantibody profiles observed in
      patients with paraneoplastic disorders imply the targeting of multiple onconeural
      antigens and predict the patient's neoplasm, but not a specific neurological
      syndrome.

PMID- 15468076
TI  - A highly efficient synthesis of the erythrina and B-homoerythrina skeleton by an
      AlMe3-mediated domino reaction.

PMID- 15468075
TI  - Huntington's Disease-like 2 (HDL2) in North America and Japan.
AB  - Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant,
      neurodegenerative disorder with marked clinical and pathological similarities to
      Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on
      chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency
      of HDL2 was determined in nine independent series of patients referred for HD
      testing or selected for the presence of an HD-like phenotype in North America or
      Japan. The repeat length, ancestry, and age of onset of all North American HDL2
      cases were determined. The results show that HDL2 is very rare, with a frequency
      of 0 to 15% among patients in the nine case series with an HD-like presentation
      who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively,
      found in individuals of African ancestry. Repeat expansions ranged from 44 to 57
      triplets, with length instability in maternal transmission detected in a repeat
      of r2=0.29, p=0.0098). The results further support the evidence that the repeat
      expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide
      preliminary guidelines for the genetic testing of patients with an HD-like
      phenotype.

PMID- 15468077
TI  - Single quantum dots in spherical silica particles.

PMID- 15468078
TI  - Metal-mediated deamination of cytosine: experiment and DFT calculations.

PMID- 15468079
TI  - Chameleon labels for staining and quantifying proteins.

PMID- 15468080
TI  - Electrophilic alkylations in neutral aqueous or alcoholic solutions.

PMID- 15468081
TI  - Novel polysilanols by selective functionalizations of oligosilanes.

PMID- 15468083
TI  - Issues of spectral quality in clinical 1H-magnetic resonance spectroscopy and a
      gallery of artifacts.
AB  - In spite of the facts that magnetic resonance spectroscopy (MRS) is applied as
      clinical tool in non-specialized institutions and that semi-automatic acquisition
      and processing tools can be used to produce quantitative information from MRS
      exams without expert information, issues of spectral quality and quality
      assessment are neglected in the literature of MR spectroscopy. Even worse, there
      is no consensus among experts on concepts or detailed criteria of quality
      assessment for MR spectra. Furthermore, artifacts are not at all conspicuous in
      MRS and can easily be taken for true, interpretable features. This article aims
      to increase interest in issues of spectral quality and quality assessment, to
      start a larger debate on generally accepted criteria that spectra must fulfil to
      be clinically and scientifically acceptable, and to provide a sample gallery of
      artifacts, which can be used to raise awareness for potential pitfalls in MRS.

PMID- 15468084
TI  - BOLD MRI mapping of transient hyperemia in skeletal muscle after single
      contractions.
AB  - Transient increases in signal intensity (DeltaSI, peak 2.6 +/- 0.6 %, mean +/-
      SE, n = 14) were observed in axial, gradient-echo, echo-planar magnetic resonance
      images acquired at 1.5 T from human anterior tibialis muscle following single, 1
      s duration, isometric ankle dorsiflexion contractions. The magnitude of the MRI
      measured DeltaSI was not significantly different using TR of 2000 vs 500 ms, or
      using spin-echo vs gradient-echo echo-planar pulse sequences. However, DeltaSI
      measured by gradient-echo sequences was significantly greater at 3 vs 1.5 T (3.8
      +/- 0.8 vs 1.6 +/- 0.2 %, n = 5). The time course of the transient DeltaSI (peak
      at 7.9 +/- 0.4 s after each contraction, decay with half-time of 4.6 +/- 0.6 s)
      was comparable to the time course of the transient increase in relative heme
      saturation (13 +/- 2 %, n = 5) measured after single contractions in another
      group of subjects by near-infrared spectroscopy (peak at 9.3 +/- 0.5 s, decay
      with half-time 6.2 +/- 0.8 s, n = 8). Simulations of intravascular and
      extravascular blood-oxygenation level-dependent (BOLD) effects in muscle
      suggested that intravascular BOLD makes a major contribution to the transient
      changes, although other factors such as increased vascular volume or increased
      muscle cell T2 may also contribute. The transients can be exploited for muscle
      functional imaging analogous to BOLD-based brain functional imaging, and might
      provide an index of peripheral vascular function.

PMID- 15468085
TI  - Minocycline prevents cholinergic loss in a mouse model of Down's syndrome.
AB  - Individuals with Down's syndrome develop Alzheimer's-like pathologies
      comparatively early in life, including progressive degeneration of basal
      forebrain cholinergic neurons (BFCNs). Cholinergic hypofunction contributes to
      dementia-related cognitive decline and remains a target of therapeutic
      intervention for Alzheimer's disease. In light of this, partial trisomy 16
      (Ts65Dn) mice have been developed to provide an animal model of Down's syndrome
      that exhibits progressive loss of BFCNs and cognitive ability. Another feature
      common to both Down's syndrome and Alzheimer's disease is neuroinflammation,
      which may exacerbate neurodegeneration, including cholinergic loss. Minocycline
      is a semisynthetic tetracycline with antiinflammatory properties that has
      demonstrated neuroprotective properties in certain disease models. Consistent
      with a role for inflammatory processes in BFCN degeneration, we have shown
      previously that minocycline protects BFCNs and improves memory in mice with
      acute, immunotoxic BFCN lesions. We now report that minocycline treatment
      inhibits microglial activation, prevents progressive BFCN decline, and markedly
      improves performance of Ts65Dn mice on a working and reference memory task.
      Minocycline is an established antiinflammatory and neuroprotective drug and may
      provide a novel approach to treat specific AD-like pathologies.

PMID- 15468087
TI  - Ionic liquids as moderators in exothermic polymerization reactions.

PMID- 15468086
TI  - Actin mutations are one cause of congenital fibre type disproportion.
AB  - We report three heterozygous missense mutations of the skeletal muscle alpha
      actin gene (ACTA1) in three unrelated cases of congenital fiber type
      disproportion (CFTD) from Japan and Australia. This represents the first genetic
      cause of CFTD to be identified and confirms that CFTD is genetically
      heterogeneous. The three mutations we have identified Leucine221Proline,
      Aspartate292Valine, and Proline332Serine are novel. They have not been found
      previously in any cases of nemaline, actin, intranuclear rod, or rod-core
      myopathy caused by mutations in ACTA1. It remains unclear why these mutations
      cause type 1 fiber hypotrophy but no nemaline bodies. The three mutations all lie
      on one face of the actin monomer on the surface swept by tropomyosin during
      muscle activity, which may suggest a common pathological mechanism. All three
      CFTD cases with ACTA1 mutations had severe congenital weakness and respiratory
      failure without ophthalmoplegia. There were no clinical features specific to CFTD
      cases with ACTA1 mutations, but the presence of normal eye movements in a severe
      CFTD patient may be an important clue for the presence of a mutation in ACTA1.

PMID- 15468088
TI  - Cross-metathesis of propane and methane: a catalytic reaction of C-C bond
      cleavage of a higher alkane by methane.

PMID- 15468089
TI  - Ru- and Rh-catalyzed C-C bond cleavage of cyclobutenones: reconstructive and
      selective synthesis of 2-pyranones, cyclopentenes, and cyclohexenones.

PMID- 15468090
TI  - Carboamination: additions of imine C=N bonds across alkynes catalyzed by
      imidozirconium complexes.

PMID- 15468091
TI  - Zirconium-mediated conversion of amides to nitriles: a surprising additive
      effect.

PMID- 15468092
TI  - Radical-mediated gamma-functionalizations of alpha,beta-unsaturated carboxylic
      amides.

PMID- 15468093
TI  - CuCl nanoplatelets from an ionic liquid-crystal precursor.

PMID- 15468094
TI  - Reversible addition fragmentation chain transfer (RAFT) polymerization from
      unprotected cadmium selenide nanoparticles.

PMID- 15468095
TI  - Mechanism of 4,6-O-benzylidene-directed beta-mannosylation as determined by alpha
      deuterium kinetic isotope effects.

PMID- 15468096
TI  - Altered decision-making in multiple sclerosis: a sign of impaired emotional
      reactivity?
AB  - We assessed decision-making capacity and emotional reactivity in 20 patients with
      multiple sclerosis (MS) and in 16 healthy subjects using the Gambling Task (GT),
      a model of real-life decision making, and the skin conductance response (SCR).
      Demographic, neurological, affective, and cognitive parameters were analyzed in
      MS patients for their effect on decision-making performance. MS patients
      persisted longer (slope, -3.6%) than the comparison group (slope, -6.4%) in
      making disadvantageous choices as the GT progressed (p < 0.001), suggesting
      significant slower learning in MS. Patients with higher Expanded Disability
      Status Scale scores (EDSS >2.0) showed a different pattern of impairment in the
      learning process compared with patients with lower functional impairment (EDSS
      </=2.0). This slower learning was associated with impaired emotional reactivity
      (anticipatory SCR 3.9 vs 6.1 microSiemens [microS] for patients vs the comparison
      group, p < 0.0001; post-choice SCR 3.9 vs 6.2 microS, p < 0.0001), but not with
      executive dysfunction. Impaired emotional dimensions of behavior (assessed using
      the Dysexecutive Questionnaire, p < 0.002) also correlated with slower learning.
      Given the considerable consequences that impaired decision making can have on
      daily life, we suggest that this factor may contribute to handicap and altered
      quality of life secondary to MS and is dependent on emotional experience. Ann
      Neurol 2004.

PMID- 15468097
TI  - The structure of obsessionality among young adults.
AB  - Although the phenomenology of obsessive-compulsive disorder (OCD) is well
      understood, less is known about the structure of obsessive symptoms in non
      clinical populations. The present study examines the factorial structure of the
      Leyton Obsessional Inventory short form (LOI-SF) in a sample of 1,015
      undergraduate college students. Four factors were extracted describing concerns
      about contamination (labeled the Contamination factor); repeating behaviors or
      uncomfortable thoughts or doubts (labeled the Doubts/Repeating factor); checking
      behaviors, too much attention to detail, honesty concerns, strict conscience and
      strict routine (labeled the Checking/Detail factor); and taking a long time to
      dress and to hang up and put away clothing, as well as belief in extremely
      unlucky numbers (labeled Worries/Just Right factor). Self-report measures of
      anxiety and ADHD symptoms were correlated positively with these factors,
      particularly with the checking/detail factor. The prevalence, symptom structure,
      and patterns of comorbidity seen in this sample of unselected college students
      are similar to the patterns seen in adolescents with OCD, suggesting that
      obsessional symptoms and OCD may exist along a continuum.

PMID- 15468100
TI  - The meaning of negative DAT SPECT and F-Dopa PET scans in patients with clinical
      Parkinson's disease.

PMID- 15468101
TI  - A new method to measure caudal motor conduction time using magnetic stimulation.
AB  - Although central motor conduction time (CMCT) has been used for the diagnosis of
      lumbosacral spinal stenosis (LSSS), its diagnostic value is limited due to the
      short length of the involved segment compared to the long length of the total
      conduction distance. To overcome this, we introduce a new method to measure the
      caudal motor conduction time (caudal MCT) using magnetic stimulation. Magnetic
      stimulation was applied to the vertex and the T12 and S1 spinous processes for
      transcortical, thoracic, and sacral stimulation, respectively, and compound
      muscle action potentials were recorded simultaneously from the rectus abdominis
      (RA) and the right and left abductor hallucis (AH) muscles using three channels.
      CMCT was calculated by the latency difference in the AH response between
      transcortical and sacral stimulation, and between transcortical and thoracic
      stimulation for RA. Caudal MCT was calculated by subtracting CMCT for RA from
      that for AH. Caudal MCT was delayed in patients with LSSS compared to normal
      persons. We suggest that measuring caudal MCT may be useful for the diagnosis of
      LSSS, but its diagnostic sensitivity and specificity requires prospective study.

PMID- 15468102
TI  - Desmin increases with high-intensity concentric contractions in humans.
AB  - To investigate the role desmin may play in muscular adaptation to exercise, we
      measured desmin protein content in the vastus lateralis muscle of seven untrained
      men in response to 8 weeks of high-intensity cycle training. Training involved 15
      s sprints separated by rest for 5 min. Subjects began with four sprints twice per
      week, and progressed to six sprints three times per week. Peak power was measured
      before and after training with a 30-s maximal sprint test. Mean power during the
      first 15 s increased significantly after training (P < 0.05). Desmin and actin
      protein levels were determined by immunoblotting, from pretraining and
      posttraining muscle biopsies. Desmin protein levels were increased by 60% after
      training (P < 0.01), whereas actin protein levels did not change with training.
      We conclude that the cytoskeletal protein desmin increases in response to a high
      tension, concentric-only load consequent to sprint training. Desmin appears to
      increase as the force generating capacity of the muscle increases. A reinforced
      desmin cytoskeleton may be necessary for increased force generation by the
      muscle.

PMID- 15468103
TI  - High-throughput chiral analysis of albuterol enantiomers in dog plasma using on
      line sample extraction/polar organic mode chiral liquid chromatography with
      tandem mass spectrometric detection.
AB  - An automated chiral chromatography/tandem mass spectrometry bioanalytical method
      for the determination of albuterol in dog plasma was developed. The method
      employed on-line sample extraction using turbulent flow chromatography coupled to
      a Chirobiotic T column for chiral separation using a polar organic mobile phase
      consisting of methanol, 0.02% formic acid, and 0.1% ammonium formate. The
      analytes were detected by a tandem mass spectrometer operated in positive ion
      mode. The (S)- and (R)-isomers were resolved chromatographically with retention
      times of 5.1 and 5.6 min, respectively. The analytical run time was 8 min. The
      enantiomers did not interconvert either in mobile phase or in dog plasma at room
      temperature over the course of at least 2 h. The assay has a linear dynamic range
      from 2.5-2500 nM for both enantiomers. The lower limit of quantitation (LLOQ) was
      2.5 nM for both enantiomers using 50 microL of plasma. The accuracy and precision
      of intraday validation were determined at five concentration levels of six
      replicates. The accuracy of the method for the (R)-isomer ranged from 94-103% of
      nominal concentrations, and the precision (%CV) ranged from 3.6-12%. The accuracy
      of the method for the (S)-isomer ranged from 94.5-108% of nominal concentrations,
      and the precision ranged from 3.2-9.3%. Interday accuracy and precision were
      evaluated for three days at five concentrations for one replicate. The accuracy
      of the method for the (R)-isomer ranged from 98-110% of nominal concentrations,
      and the precision ranged from 1.5-10.6%. The accuracy of the method for the (S)
      isomer ranged from 96-104% of nominal concentrations, and the precision ranged
      from 1.5-8.7%. The combination of turbulent flow on-line sample extraction with
      polar organic mode chiral chromatography provided a specific, rugged, and high
      throughput method for the chiral analysis of albuterol in biological fluids.

PMID- 15468104
TI  - Optimization of quadrupole ion storage mass spectrometric conditions for the
      analysis of selected polybrominated diphenyl ethers. Comparative approach with
      negative chemical ionization and electron impact mass spectrometry.
AB  - Gas chromatography coupled to quadrupole ion storage mass spectrometry (QISTMS)
      operating in the non-resonant mode is presented as an innovative approach for the
      analysis of selected polybrominated diphenyl ethers (PBDEs). Although reductions
      in complexity and time needed for optimization are achieved in comparison with
      the resonant option, precise adjustment of the mass spectrometric conditions is
      required. Differences in isolation and fragmentation patterns of target species
      with degree of bromination were observed. The reliability of the method was
      confirmed by using standard solutions through the evaluation of certain quality
      parameters such as accuracy (92-108%), injection repeatability and
      reproducibility (coefficient of variation below 10% and 15%, respectively).
      Detection limits ranged from 62 to 621 fg, providing sensitivity similar to that
      of negative chemical ionisation (NCIMS) and greater than that of electron
      ionization mass spectrometry. The applicability of QISTMS method to real samples
      and matrix effects were evaluated through the analysis of some PBDE congeners in
      a sewage sludge sample from a Spanish waste-water treatment plant. Comparable
      results were obtained using QISTMS and NCIMS. According to these observations,
      QISTMS performed in the non-resonant mode may constitute a low-cost, rapid and
      reliable alternative to high-resolution devices for the analysis of selected
      PBDEs in environmental samples.

PMID- 15468105
TI  - Photoelectron resonance capture ionization mass spectrometry: a soft ionization
      source for mass spectrometry of particle-phase organic compounds.
AB  - Photoelectron resonance capture ionization (PERCI) is a soft and sensitive
      ionization method, based on the attachment of low-energy (<1 eV) photoelectrons
      to organic analyte molecules. PERCI has been developed in our laboratory for the
      real-time analysis of organic particles by mass spectrometry, and is employed
      here to monitor the heterogeneous reaction of ozone with oleic acid. Simplified
      identification of the reaction products is possible as a result of the soft
      nature of PERCI, giving predominantly the [M--H](-) ions. The major particle
      phase products are identified as: 1-nonanal, nonanoic acid, 9-oxononanoic acid,
      and azelaic acid, consistent with proposed mechanisms. New insight into this well
      studied heterogeneous reaction is gained as additional minor particle-phase
      products, consistent with the Criegee mechanism, are readily detected.

PMID- 15468106
TI  - Proteomic analysis of mouse liver for the evaluation of effects of Scutellariae
      radix by liquid chromatography with tandem mass spectrometry.
AB  - Scutellariae radix or Scutellaria baicalensis is a medicinal plant that contains
      major flavonoids such as baicalein, baicalin, wogonin and wogonosides. The
      present work describes the development of an approach using proteomic analysis of
      mouse liver to study the effects of prolonged exposure to substances present in
      chemically standardized Scutellariae radix extracts. Histopathological
      examination of the mouse liver was compared with the proteome data. The botanical
      extracts were prepared using pressurized liquid extraction (PLE). A method
      without isotope labeling was developed, using proteolytic digestion with one- and
      two-dimensional liquid chromatography with tandem mass spectrometry, and was used
      to characterize the extent of differential protein expression in mouse liver in
      response to external factors such as extracts from Scutellariae radix. From the
      histopathological examination and proteome data, significant changes in the mouse
      livers were not observed for the low-dose group. The Scutellariae radix extracts
      at high dose were observed to cause damage at the bile duct and expression change
      of a number of proteins including some involved in catabolism of triglyceride
      rich particles, carbohydrate metabolism, regulators of cell signaling processes,
      and enzymes involved in biotransformation. Thus, proteomic analysis of liver
      samples from mice treated with botanical extracts is a promising approach to
      provide information on any potential toxicity effects of the extracts. The
      present method also provides another means for comparing proteomes in biological
      samples such as liver lysates from mice subjected to different treatments.

PMID- 15468107
TI  - Electrospray mass and tandem mass spectrometry of homologous and isomeric singly,
      doubly, triply and quadruply charged cationic ruthenated meso-(phenyl)m-(meta-
      and para-pyridyl)n (m + n = 4) macrocyclic porphyrin complexes.
AB  - Ten homologous or isomeric singly, doubly, triply and quadruply charged cationic
      macrocyclic complexes I-Va, bn+ (n = 1-4) formed by the coordination of
      [Ru(bipy)2Cl]+ to the pyridyl N-atoms of a series of meso-(phenyl)m-(meta or para
      pyridyl)n-porphyrins (m + n = 4) were transferred to the gas phase and
      structurally characterized by electrospray ionization (ESI) mass (MS) and tandem
      mass (MS/MS) spectrometry. Previously known to be stable in solution and in the
      solid state, I-Va, bn+ are found to constitute also a new class of stable, long
      lived multiply charged gas-phase ions with spatially separated charge sites.
      Increasing intramolecular electrostatic repulsion from Ia, b+ to IVa, b3+
      facilitates in-source and tandem collision-induced dissociation (CID). However,
      for the quadruply charged ions Va, b4+, electrostatic repulsion is alleviated
      mainly by ion pairing with the CF3SO3- counterion forming the salt clusters
      [Va,b/CF3SO3]3+ and [Va,b/(CF3SO3)2]2+ with reduced charge states. Ion-pairing
      that yields [IVa,b/CF3SO3]2+ is also observed as a minor ESI process for the
      triply charged ions IVa, b3+. The gaseous ions I-Va, bn+ (n = 2, 3 or 4)
      dissociate by sequential 'charge partitioning' with the formation of two cationic
      fragments by the release of [Ru(bipy)2Cl]+. The meta (a) and para (b) isomers and
      the positional isomers II2+ and III2+ display nearly identical ESI-MS and ESI
      MS/MS spectra. ESI-MS/MS of I-Va, bn+ shows that the Ru-py(P) is, intrinsically,
      the weakest bond since this bond breaks preferentially upon CID.

PMID- 15468109
TI  - No global loss of neocortical neurons in Parkinson's disease: a quantitative
      stereological study.
AB  - The global total number of neocortical neurons was estimated in 10 patients with
      Parkinson's disease (PD; mean age, 74.8 years; range, 68-83) and compared to 12
      comparison subjects (mean age, 75.8 years; range, 70 - 84). The total mean
      neocortical neuron number in the patients with PD was 18.6 x 10(9) with a
      coefficient of variation (CV = SD/mean) of 0.18, which was not statistically
      significantly different from that of the controls (18.8 x 10(9); CV = 0.16; P =
      0.90). In contrast to some studies reporting neocortical atrophy this was not
      confirmed in our study, where the mean volume of neocortex was the same in the
      two groups (P = 0.59). No difference was found in the volume of white matter,
      central gray structures, archicortex, or the ventricular system between the two
      groups. Most patients with PD develop cognitive disturbances with time, and this
      study cannot exclude that local neuron loss in specific subpopulations of
      neocortical neurons or cell loss in small but essential neocortical subregions
      may be part of the structural defects of PD.

PMID- 15468110
TI  - Calibration and validation of confocal spectral imaging systems.
AB  - BACKGROUND: Confocal spectral imaging (CSI) microscopic systems currently on the
      market delineate multiple fluorescent proteins, labels, or dyes within biological
      specimens by performing spectral characterizations. However, some CSI systems
      have been found to present inconsistent spectral profiles of reference spectra
      within a particular system and between related and unrelated instruments. This
      variability confirms that there is a need for a standardized, objective
      calibration and validation protocol. METHODS: Our protocol uses an inexpensive
      multi-ion discharge lamp (MIDL) that contains Hg(+), Ar(+), and inorganic
      fluorophores that emit distinct, stable, spectral features in place of a sample.
      We derived reference spectra from the MIDL data to accurately predict the
      spectral resolution, ratio of wavelength to wavelength, contrast, and aliasing
      parameters of any CSI system. We were also able to predict and confirm the
      influence of pinhole diameter on spectral profiles. RESULTS: Using this
      simulation, we determined that there was good agreement between observed and
      theoretical expectations, thus enabling us to identify malfunctioning subsystems.
      We examined eight CSI systems and one nonconfocal spectral system, all of which
      displayed spectral inconsistencies. No instrument met its optimal performance
      expectations. In two systems, we established the need for factory realignment
      that had not been otherwise recognized. CONCLUSIONS: We found that using a
      primary light source that emits an absolute standard "reference spectrum" enabled
      us to diagnose instrumental errors and measure accuracy and reproducibility under
      normalized conditions. With this information, a CSI operator can determine
      whether a CSI system is working optimally and make objective comparisons with the
      performance of other CSI systems. We determined that, if CSI systems were
      standardized to produce the same spectral profile of a MIDL lamp, researchers
      could be confident that the same experimental findings would be obtained on any
      CSI system.

PMID- 15468111
TI  - Cigarette smoking and Parkinson's disease: a case-control study in a population
      characterized by a high prevalence of pesticide exposure.
AB  - Epidemiological studies have been consistent in showing that cigarette smoking is
      inversely associated with Parkinson's disease (PD), whereas pesticide use is
      positively associated with PD. However, the relationship between PD and cigarette
      smoking remains poorly understood. Our objective was to study the relationship
      between cigarette smoking and PD in a population characterized by a high
      prevalence of pesticide exposure. This case-control study was carried out among
      subjects enrolled in the Mutualite Sociale Agricole, the French health insurance
      organization for workers connected to the agricultural world. We included 247
      cases and 676 controls matched on age, sex, and region of residency. Information
      on smoking was obtained through in-person interviews. Pesticide exposure was
      assessed using a case-by-case expert evaluation procedure. We found an inverse
      relationship between ever cigarette smoking and PD (odds ratio [OR] = 0.6; 95%
      confidence interval [CI] = 0.4-0.9). The strength of this association increased
      with the number of pack-years. This relationship was present even when smoking
      was considered as long as 40 years before PD onset. An inverse association was
      also present among subjects professionally exposed to pesticides (OR = 0.5; 95%
      CI = 0.3-0.8) and was independent of the duration of exposure among men. We
      confirm the inverse association between cigarette smoking and PD in a population
      characterized by a high prevalence of professional pesticide exposure. The
      relationship between PD and cigarette smoking was not significantly modified or
      confounded by exposure to pesticides.

PMID- 15468113
TI  - Evidence for linkage position determination in known feruloylated mono- and
      disaccharides using electrospray ion trap mass spectrometry.
AB  - Various feruloylated arabinose- and galactose-containing mono- and disaccharides
      with known linkage configurations (2-O-(trans-feruloyl)-L-arabinopyranose, 5-O
      (trans-feruloyl)-L-arabinofuranose, O-[2-O-(trans-feruloyl)-alpha-L
      arabinofuranosyl]-(1-->5)-L-arabinofuranose, and O-[6-O-(trans-feruloyl)-beta-D
      galactopyranosyl]-(1-->4)-D-galactopyranose) were analyzed by electrospray
      ionization mass spectrometry using an ion trap or a quadrupole time-of-flight (Q
      TOF) mass analyzer. Collision-induced dissociation (CID) experiments using the
      two mass analyzers generated similar tandem mass spectrometric (MS/MS)
      fragmentation patterns. However, the ester-bond cleavage ions were more abundant
      using the Q-TOF mass analyzer. Compared with the positive ion mode, the negative
      ion mode produces simpler and more useful CID product-ion patterns. For arabinose
      containing feruloylated compounds, results obtained with both analyzers show that
      it is possible to assign the location of the feruloyl group to the O-2 or O-5 of
      arabinosyl residues. In the characterization of the 2-O-feruloyl and 5-O-feruloyl
      linkages, the relative abundance of the cross-ring fragment ions at m/z 265 (-60
      u or -62 u after 18O-labelling) and at m/z 217 (-108 u or -110 u after 18O
      labelling) play a relevant role. For galactose-containing feruloylated compounds,
      losses of 60, 90 and 120 Da observed in MS3 experiment correspond to the
      production of 0,2A1, 0,3A1 and (0,2A1-60 Da) cross-ring cleavage ions,
      respectively, fixing the location of feruloyl group at the O-6 of the galactose
      residue.

PMID- 15468114
TI  - Does the fine-needle aspiration diagnosis of "Hurthle-cell neoplasm/follicular
      neoplasm with oncocytic features" denote increased risk of malignancy?
AB  - The thyroid fine-needle aspiration (FNA) diagnosis of Hurthle-cell neoplasm
      (HCN)/follicular neoplasm with oncocytic features (FNOF) does not differentiate
      between Hurthle-cell adenoma and carcinoma. A majority of cases diagnosed as HCN
      undergo surgical excision for definite characterization. The aim of this study
      was to determine the risk of malignancy in cases diagnosed as HCN and identify
      clinical features that may help in predicting malignancy in patients with FNA
      diagnosis of HCN. We reviewed a cohort of 206 cases of thyroid FNA diagnosed as
      HCN; histological follow-up was available in 169 (82%) cases. The cases were
      evaluated for patient's age, sex, and size of the nodule and histological
      diagnosis. One hundred and sixty-six were female patients and 40 were male
      patients (age range, 12-83 yr). The histological diagnoses were benign in 93
      (93/169, 55%) cases and malignant in 76 (76/169, 45%) cases. The malignant
      histological diagnoses were Hurthle-cell carcinoma (HCC), 53 cases; papillary
      thyroid carcinoma, 19 cases; follicular carcinoma, 3 cases; and medullary
      carcinoma, 1 case. The risk of malignancy was greater in nodules measuring > or
      =2 cm (55% vs. 45%; P value < 0.0001) in patients who were > or =40 yr old (82%
      vs. 18%, P value < 0.0001) than in patients <40 yr. The risk of malignancy was
      found greater in male patients than in female patients (61% vs. 43%); however,
      the difference was not statistically significant. The diagnosis HCN/FNOF carries
      a higher risk of malignancy as compared with a diagnosis of follicular
      lesion/neoplasm (20% malignancy rate from previously published studies). Clinical
      features including size of the nodule, age, and possibly sex of the patient can
      be a part of the decision analysis in selecting a patient for surgery.

PMID- 15468115
TI  - Human T-lymphotropic virus type-1 related adult T-cell leukemia/lymphoma
      presenting as a parotid mass diagnosed by fine-needle aspiration biopsy.
AB  - A 48-yr-old black woman with a history of blood transfusions for menorrhagia
      secondary to uterine fibroids but no known Caribbean association presented with a
      6-wk history of a rapidly enlarging right parotid mass. At the time of
      presentation, she could not close her right eye. An aspiration biopsy showed
      small, medium, and large lymphoma cells with angulated nuclei, red macronucleoli,
      and basophilic cytoplasm with fine vacuoles. Flow cytometry indicated a
      (CD25(+)/CD7(-)) T-cell lineage, suggesting an human T-lymphotropic virus (HTLV)
      1-related T-cell leukemia/lymphoma, which was confirmed by polymerase chain
      reaction (PCR)-based amplification on DNA extracted from fresh tissue with
      specific oligonucleotide primers for HTLV-1 DNA sequence. Histology showed
      interstitial infiltration and destruction of the parotid parenchyma by lymphoma
      cells without involvement of adjacent lymph nodes. Total body CT scan and
      magnetic resonance imaging (MRI) studies were negative for lymphadenopathy but
      showed liver metastasis. To our knowledge, this is the first reported case of
      HTLV-1-related primary parotid lymphoma as the initial presentation of adult T
      cell leukemia/lymphoma.

PMID- 15468116
TI  - Fine-needle aspiration of subcutaneous panniculitis-like T-cell lymphoma.
AB  - We report the fine-needle aspiration (FNA) cytology findings of Subcutaneous
      Panniculitis-like T-cell Lymphoma (SCPTCL) in a 66-year-old woman who presented
      with a four month history of asymptomatic subcutaneous nodules on her right chest
      wall and back. An excisional biopsy of the right chest nodules was performed, and
      the diagnosis of SCPTCL was rendered. On a follow-up visit, several skin lesions
      were noted throughout her body. A fine-needle aspiration (FNA) of the right
      inguinal region was performed. The FNA yielded cellular smears, composed mainly
      of sheets of epithelioid histiocytes and scattered multinucleated cells. However,
      no distinct granulomas were noted. The background of the cytological smears
      showed scattered atypical lymphoid cells, some of which displayed nuclear
      membrane irregularities. To the best of our knowledge, the cytological features
      on FNA material of SCPTCL have not been described.

PMID- 15468117
TI  - Superficial malignant neoplasms in southwestern Ethiopia: a cytopathological
      approach.
AB  - The aim of this study was to describe the distributions of superficial malignant
      neoplasms diagnosed by fine-needle aspiration cytology (FNAC). A prospective
      cross-sectional study was conducted within the Jimma Teaching Hospital, Pathology
      Department, Jimma University during the years between September 1998 and August
      2002. Cases fulfilling cytopathological evidences of superficial malignancies
      were included whereas deep-seated malignancies were excluded from the study. An
      air-dried smear stained with the Wright staining procedure was utilized for the
      FNAC diagnostic technique. A total of 3,200 cases were investigated during the
      study period where 267 (8.3%) cases were of primary superficial malignant
      neoplasms, with 98 cases in the peak age group of 40-59 yr (36.7%) and a median
      age of 38.0 yr (range, 0.2-88 yr). The most frequent superficial cytodiagnosis
      was breast carcinoma, 79 (29.6%) cases; followed by non-Hodgkin's lymphomas, 37
      (13.9%) cases; and soft tissue sarcomas, 26 (9.7%) cases. The overall male-to
      female ratio showed preponderance to female patients (1:1.3). Carcinomas were
      identified more frequently in those >40 yr of age whereas sarcomas were
      identified in those <40 yr of age (P > 0.05). The most common malignant neoplasm
      in women was breast carcinomas found in 74 (27.7%) cases, whereas in men non
      Hodgkin's lymphomas were found in 29 (10.9%) cases. Large proportions of
      carcinomas (88 cases, 33.0%), lymphomas (33 cases, 12.4%), and sarcomas (20
      cases, 7.5%) were detected on the trunk, head, and neck, as well as on the lower
      limb regions, respectively. This study uncovered different types of superficial
      malignant neoplasms that are prevalent in the southwestern part of Ethiopia. The
      most common types of cytodiagnoses such as breast carcinomas, etc. may suggest
      that attention be given to future high-caliber prospective studies in trying to
      identify some of the associated strong risk factors for the disease under study.
      This study may be helpful to local health planners in prioritizing some of the
      commonest malignancies. Some of the diagnostic challenges of lymphomas and
      thyroid follicular lesions were shown also. This investigation is the first in
      Ethiopia and therefore may act as baseline data for similar studies in the
      future.

PMID- 15468118
TI  - Nonepithelial malignancies mimicking primary carcinoma of the breast.
AB  - Although primary carcinomas account for the majority of breast malignancies,
      nonepithelial malignancies form a subset that must be differentiated accurately
      for treatment purposes. The purpose of this study was to identify cytological
      characteristics that differentiate between these two entities. Twenty-six fine
      needle aspiration (FNA) specimens with histological correlation were reviewed
      (five lymphomas, two myelomas, six sarcomas, seven melanomas, and six
      carcinomas). On review, nonepithelial tumors presented as single cells with scant
      or ill-defined cytoplasm with rare cluster formations present. In contrast,
      carcinomas were arranged predominantly in clusters and contained more-defined,
      abundant, and sometimes vacuolated cytoplasm. Moreover, a major aid to diagnosis
      was an accurate clinical history. We conclude that nonepithelial malignancies of
      the breast are best differentiated from epithelial malignancies by a combination
      of cytological features and clinical information. These findings emphasize the
      importance of the triple test, in which integration of cytological findings and
      clinical information play a key role.

PMID- 15468119
TI  - Artifacts of cytology cell block in fine-needle aspiration biopsy of thyroid.

PMID- 15468120
TI  - Fine-needle aspiration cytology of Merkel cell carcinoma.

PMID- 15468121
TI  - Sparse imaging and continuous event-related fMRI in the visual domain: a
      systematic comparison.
AB  - Continuous image acquisition as used in most functional magnetic resonance
      imaging (fMRI) designs may conflict with specific experimental settings due to
      attendant, noisy gradient switching. In sparse fMRI, single images are recorded
      with a delay that allows the registration of the predicted peak of an evoked
      hemodynamic response (HDR). The aim of this study was to assess validity and
      sensitivity of single-trial sparse imaging within the visual domain. Thirteen
      subjects were scanned twice. Either continuous or sparse image acquisition was
      applied while participants viewed single trains of flashlights. Sparse fMRI
      results were compared to continuous event-related fMRI results on single- and
      multisubject level regarding spatial extent, overlap, and intensity of
      activation. In continuously recorded data, the variability of the HDR peak
      latency was examined because this measure determined the timing of sparse image
      acquisition. In sparse fMRI, the sensitivity was analyzed considering different
      numbers of averaged trials. Sparse imaging detected the core activity revealed
      using continuous fMRI. The intensity of signal changes detected by continuous or
      sparse fMRI was comparable. The HDR peak latency was stable across sessions, but
      intersubject and regional variability might have affected the power of sparse
      fMRI. In sparse imaging, adding trials resulted in extension of activation and
      improvement in statistical power. The comparison with established continuous fMRI
      confirms the validity of sparse imaging. Conventional event-related data
      acquisition and analysis provided more comprehensive results. However, only
      sparse fMRI offers the opportunity to apply stimuli and record further biosignals
      free of scanner-related artifacts during intervals without image acquisition.

PMID- 15468122
TI  - Formal characterization and extension of the linearized diffusion tensor model.
AB  - We analyzed the properties of the logarithm of the Rician distribution leading to
      a full characterization of the probability law of the errors in the linearized
      diffusion tensor model. An almost complete lack of bias, a simple relation
      between the variance and the signal-to-noise ratio in the original complex data,
      and a close approximation to normality facilitated estimation of the tensor
      components by an iterative weighted least squares algorithm. The theory of the
      linear model has also been used to derive the distribution of mean diffusivity,
      to develop an informative statistical test for relative lack of fit of the
      ellipsoidal (or spherical) model compared to an unrestricted linear model in
      which no specific shape is assumed for the diffusion process, and to estimate the
      signal-to-noise ratios in the original data. The false discovery rate (FDR) has
      been used to control thresholds for statistical significance in the context of
      multiple comparisons at voxel level. The methods are illustrated by application
      to three diffusion tensor imaging (DTI) datasets of clinical interest: a healthy
      volunteer, a patient with acute brain injury, and a patient with hydrocephalus.
      Interestingly, some salient features, such as a region normally comprising the
      basal ganglia and internal capsule, and areas of edema in patients with brain
      injury and hydrocephalus, had patterns of error largely independent from their
      mean diffusivities. These observations were made in brain regions with
      sufficiently large signal-to-noise ratios (>2) to justify the assumptions of the
      log Rician probability model. The combination of diffusivity and its error may
      provide added value in diagnostic DTI of acute pathologic expansion of the
      extracellular fluid compartment in brain parenchymal tissue.

PMID- 15468125
TI  - Determination of paraquat and diquat in human body fluids by high-performance
      liquid chromatography/tandem mass spectrometry.
AB  - Paraquat (PQ) and diquat (DQ) in human whole blood and urine were analyzed by
      high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) with
      positive ion electrospray ionization (ESI). The compounds were extracted with Sep
      Pak C18 cartridges from whole blood and urine samples containing ethyl paraquat
      as an internal standard. The separation of PQ and DQ was carried out using ion
      pair chromatography with heptafluorobutyric acid in 20 mM ammonium acetate and
      acetonitrile gradient elution for successful coupling with MS. Both compounds
      formed base peaks due to [M-H]+ ions by HPLC/ESI-MS and the product ions produced
      from each [M-H]+ ion by HPLC/MS/MS. Selective reaction monitoring (SRM) showed
      much higher sensitivity for both body fluids. Therefore, a detailed procedure for
      the detection of compounds by SRM with HPLC/MS/MS was established and carefully
      validated. The recoveries of PQ and DQ were 80.8-95.4% for whole blood and 84.2
      96.7% for urine. The calibration curves for PQ and DQ showed excellent linearity
      in the range of 25-400 ng ml(-1) of whole blood and urine. The detection limits
      were 10 ng ml(-1) for PQ and 5 ng ml(-1) for DQ in both body fluids. The intra-
      and inter-day precision for both compounds in whole blood and urine samples were
      not greater than 13.0%. The data obtained from the determination of PQ and DQ in
      rat blood after oral administration of the compounds are also presented.

PMID- 15468123
TI  - Rapid detection of phosphotyrosine proteins by flow cytometric analysis in Bcr
      Abl-positive cells.
AB  - BACKGROUND: Constitutive tyrosine phosphorylation derived from Bcr-Abl kinase
      activity is the major characteristic of Bcr-Abl positive cells. In this study, we
      developed a method to detect the phosphotyrosine proteins by flow cytometry and
      we asked whether phosphorylation was affected by imatinib mesylate treatment.
      METHODS: Cells were treated or not with imatinib mesylate, fixed and
      permeabilized by PFA followed by saponin, then stained with anti-phosphotyrosine
      (p-tyr) monoclonal antibody and analyzed by flow cytometry. RESULTS: Optimal
      staining parameters were performed with p-tyr antibody using K562 and LAMA84
      lines that displayed high levels of tyrosine phosphorylation as compared to the
      control line, HL60. Tyrosine phosphorylation was inhibited by imatinib in a dose
      dependent manner, but not modified by other inhibitors demonstrating that the
      staining detected is specific to Bcr-Abl phosphorylation. The staining of
      imatinib-resistant cell lines such as the mutated BaF/Bcr-AblT315I cell line or
      resistant CML patient cells, showed that hyperphosphorylation was not affected by
      imatinib treatment. In one CML patient, our technique permitted us to detect a
      small hyperphosphorylated population resistant to imatinib that appeared
      hyperphosphorylated and amplified at the time of relapse. CONCLUSIONS: We have
      developed a flow cytometric technique presenting several advantages such as
      rapidity and sensitivity, which requires fewer cells than the Western blot.

PMID- 15468126
TI  - Metastatic extraocular sebaceous carcinoma with an occult primary.
AB  - The cytological diagnosis of sebaceous carcinoma is based on the aspiration of
      tumor lobules with extensive sebaceous differentiation. However, these tumors may
      show a spectrum of cells ranging from basaloid to well-differentiated sebaceous.
      Extraocular sebaceous carcinoma is an uncommon tumor. An occult primary at
      initial presentation has not been described previously. A 60-yr old woman was
      referred to the fine-needle aspiration (FNA) clinic with a submandibular mass.
      The cytological diagnosis was mucoepidermoid carcinoma. Histopathologically, it
      was a sebaceous carcinoma metastatic to the submandibular lymph node. No primary
      tumor was identified. Six months later, she presented with a nodule at the angle
      of her mouth and a recurrence of the submandibular swelling. FNA cytology (FNAC)
      and histopathologic examination revealed a primary cutaneous sebaceous carcinoma
      with submandibular lymph node metastasis. A metastatic sebaceous carcinoma in the
      submandibular region with limited sebaceous differentiation and occult primary is
      another pitfall in the cytomorphological diagnosis of mucoepidermoid carcinoma.

PMID- 15468127
TI  - Sclerosing lobular hyperplasia of the breast: fine-needle aspiration cytology
      findings--a case report.
AB  - Sclerosing lobular hyperplasia (SLH) is an uncommon benign lesion seen in the
      juvenile breast. It presents as a palpable, firm, circumscribed nodular lump in
      the breast of a young woman. Histologically, it is characterised by prominent
      lobular hyperplasia and sclerosis of the intralobular connective tissue. We
      discuss the cytomorphology and differential diagnosis. A 16-yr-old female patient
      presented with a painless, firm, nodular, mobile mass in the right breast
      measuring 4 x 4 cm. The clinical and radiological diagnosis was fibroadenoma.
      Fine-needle aspiration smears showed round to oval ductal epithelial cells in
      flat sheets and round clusters with an acinar arrangement. A few bare nuclei were
      seen dispersed in a clean background but no stroma was visualised. A combination
      of clinical findings, imaging, and cytological features of SLH can help to
      differentiate this condition from other palpable juvenile breast diseases.

PMID- 15468128
TI  - Repair renal tubular cells: a potential false-positive diagnosis in urine
      cytology.
AB  - To study the cytopathology of repair renal tubular cells (RRTCs), the
      Papanicolaou-stained urine sediments of 371 patients with mild and moderate renal
      tubular injuries were reviewed. In 46 cases, the urine sediments showed, in
      addition to a mild or moderate increase in number of RTCs, a few isolated and
      clustered RRTCs that displayed well- or ill-defined, variably abundant, granular
      or vacuolated cytoplasm; slightly pleomorphic nuclei; and conspicuous or
      prominent nucleoli. A spectrum of nuclear changes ranging from mild to moderate
      atypias and/or severe atypia were present in many cases. These RRTCs stained
      strongly positively with vimentin antibody in 92.3% of the cases.

PMID- 15468129
TI  - ASC-US and HPV testing in women aged 40 years and over.
AB  - High-risk human papillomavirus (HPV) DNA triage is commonly performed for
      cervical cytology specimens interpreted as atypical squamous cells of
      undetermined significance (ASC-US), but little is known about testing results in
      women > or =40 yr of age. The extent to which clinical follow-up after HPV
      testing reflects the most recent management guidelines is unknown also. Data from
      108 patients > or =40 yr of age with concurrent (93 patients) or recent (15
      patients) ASC-US interpretations and HPV testing were reviewed. Twenty-five
      (23.1%) of these patients were positive for high-risk HPV. The HPV(+) rate was
      higher in women with a current interpretation of ASC-US (26.9%) compared with
      those with a previous ASC-US result (0%). Many patients were not managed exactly
      according to the "2001 Consensus Guidelines for the Management of Women with
      Cervical Cytologic Abnormalities." The majority (52.6%) of women with HPV(+) ASC
      US did not receive colposcopy in our institution, and 41.3% of women with HPV(-)
      ASC-US received follow-up testing within 8 mo. These results show the potential
      for inadequate evaluation of women with HPV(+) ASC-US, as well as unnecessary
      early repeat cytology in HPV(-) ASC-US patients. Therefore, additional clinician
      education and reminders to correlate cytology and HPV test results may be
      warranted to optimize patient care.

PMID- 15468130
TI  - Cytology of benign breast lesions.

PMID- 15468131
TI  - The significance of the diagnosis of atypia in breast fine-needle aspiration.
AB  - The diagnosis of atypia in breast fine-needle aspiration (FNA) continues to be an
      area of debate in cytology practice. The aim of this study was to assess the
      clinical significance of this term and to evaluate potential morphological
      criteria, which would determine the patient's outcome. A computer-based search
      was carried out to retrieve breast FNAs performed between 1990 and 2000 that were
      diagnosed as atypical. Cases followed by surgical resection were reexamined for
      the presence of morphological features potentially differentiating benign and
      malignant lesions. Out of 1,568 breast FNAs, there were 64 cases (4%) with a
      diagnosis of atypia. Thirty-eight cases had surgical follow-up material that
      revealed malignancy in 14 cases (37%) and benign lesions in 24 cases (63%). The
      benign diagnostic categories included fibrocystic change (12/24), fibroadenoma
      (3/24), tubular adenoma (2/24), and nonspecific findings (7/24). The malignant
      diagnoses included ductal carcinoma (9/14), lobular carcinoma (3/14), ductal
      carcinoma in situ (DCIS; 1/14), and tubular carcinoma (1/14). The evaluation of
      cytological criteria used to differentiate benign from malignant lesions (i.e.,
      cellularity, loss of cohesion, myoepithelial cells, nuclear enlargement, nuclear
      overlap, prominent nucleoli) revealed significant overlap between benign and
      malignant cases, particularly in cases of fibroadenoma, tubular adenoma, and
      proliferative breast disease. The surgical follow-up of four hypocellular cases
      revealed lobular carcinoma in two cases and ductal carcinoma in the remaining two
      cases. Our study confirmed that the diagnosis of atypia is clinically significant
      because it is associated with a high probability of malignancy. No morphological
      criterion is able to reliably differentiate benign and malignant lesions in cases
      diagnosed with atypia. Diagnosis of atypia is particularly significant in
      hypocellular cases. We recommended that breast FNAs with a diagnosis of atypia be
      evaluated further histologically.

PMID- 15468132
TI  - Diagnostic value of GLUT-1 immunoreactivity to distinguish benign from malignant
      cystic squamous lesions of the head and neck in fine-needle aspiration biopsy
      material.
AB  - The distinction of cystic squamous-cell carcinoma (SCC) from benign cystic
      squamous lesions (BCSLs) of the head and neck can be problematic on fine-needle
      aspiration biopsy (FNAB) material, particularly when BCSLs display epithelial
      reactive atypia or when SCC is well differentiated. Glucose transporter 1 (GLUT
      1), a facilitative cell surface glucose transport protein, is aberrantly
      expressed in many cancers including oral and hypopharyngeal SCC. We evaluated the
      expression of GLUT-1 by immunochemistry on FNAB material to determine its value
      in distinguishing cystic SCC from BCSL of the head and neck. A 5-yr retrospective
      review of all head and neck cystic squamous lesions having FNAB specimens with
      cell block material, radiological studies, and histological confirmation was
      performed at our institution. Cell block material from 24 cystic squamous
      lesions, including 8 (33%) BCSL (7 branchial cleft cysts and 1 thyroglossal duct
      cyst[TDC]) and 16 (67%) metastatic SCCs with cystic/liquefactive degeneration,
      was retrieved and immunostained with anti-GLUT-1. GLUT-1 expression was
      considered positive when at least 10% of squamous cells exhibited distinct cell
      membrane reactivity. Positive GLUT-1 immunostaining was detected in all 16 SCCs
      and in none of the 8 BCSLs. In the carcinoma cases, the majority of malignant
      cells exhibited GLUT-1 reactivity; only a minor population of well-differentiated
      SCC cells displaying keratinization and arranged as squamous pearls did not
      express GLUT-1. GLUT-1 expression in cell block material can help to distinguish
      cystic SCCs from BCSLs of the head and neck. In conjunction with clinical and
      radiological correlation, GLUT-1 immunoreactivity can be an important diagnostic
      aid when the cytological findings are ambiguous.

PMID- 15468133
TI  - A simple method to determine the need for glacial acetic acid treatment of bloody
      ThinPrep Pap tests before slide processing.
AB  - ThinPrep (TP) Papanicolaou (Pap) samples containing excessive blood often result
      in unsatisfactory preparations, possibly leading to undetected gynecologic
      disease, and added inconvenience to patients and clinicians. Reprocessing of
      these samples with a glacial acetic acid wash is effective at eliminating blood,
      providing satisfactory preparation and detection of lesions. However, it
      increases laboratory costs and decreases work flow efficiency. We report the use
      of a color standard for gauging the necessity of performing a glacial acetic acid
      wash before TP processing. This "preprocessing" was found to reduce the costs
      associated with reprocessing by 48%, while maintaining high preparation quality
      by improved sample adequacy.

PMID- 15468134
TI  - Diagnosis of nonprimary pancreatic neoplasms by endoscopic ultrasound-guided fine
      needle aspiration.
AB  - Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a proven
      modality for the diagnosis of primary pancreatic neoplasms. We describe our
      experience in diagnosing nonprimary pancreatic tumors by EUS-FNA. Cytology files
      were searched for all EUS-FNA of the pancreas for the period 2000-2002. All cases
      diagnosed as neoplasms were selected and those diagnosed as nonprimary pancreatic
      tumors were reviewed and analyzed. One hundred ninety-one of 468 cases were
      diagnosed as neoplasms. Eleven of these cases were diagnosed as nonprimary
      pancreatic tumors (2.4% of all diagnoses and 5.7% of all neoplasms). The
      diagnoses were supported by clinical history (n = 7), cytological findings (n =
      11), cell block histology (n = 11), cell block immunohistochemistry (n = 6), and
      flow cytometry (n = 1). EUS-FNA is a safe and minimally invasive method for the
      diagnosis of nonprimary pancreatic neoplasms. Evaluation of clinical history,
      cytomorphology, and ancillary techniques, especially those applied to cell block
      material, are essential for accurate diagnoses.

PMID- 15468135
TI  - Collagenous bodies in endometriotic cysts.
AB  - A 4-yr retrospective analysis of cases diagnosed as pelvic endometriotic cysts
      based on clinical, radiological, and cytomorphological features was collected and
      analysed. Out of 15 cases, only 3 cases showed the presence of endometrial
      glands/stroma in the aspiration smears. However, 12 of them showed the presence
      of oval/petal-shaped structures throughout the smear ranging in size from 40 to
      70 micro in maximum dimension. These structures stained positive with periodic
      acid Schiff (PAS) stain. Immunostaining for type IV collagen showed strong
      positivity, indicating their origin from the basement membrane of the glands. The
      presence of these "collagenous bodies" in endometriotic cysts appears to be
      characteristic. However, this needs to be confirmed by prospective studies with a
      larger number of patients. The mechanism of formation of these collagenous bodies
      is uncertain.

PMID- 15468136
TI  - Laccase-catalyzed mediated oxidation of benzyl alcohol: the role of TEMPO and
      formation of products including benzonitrile studied by nanoelectrospray
      ionization Fourier transform ion cyclotron resonance mass spectrometry.
AB  - Substituted benzyl alcohol was oxidized enzymatically with a laccase-mediator
      system and the products were investigated as a function of time by
      nanoelectrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry (nanoESI-FTICRMS). With Trametes versicolor laccase (TVL), the
      mediator, 2,2',6,6'-tetramethylpiperidine-N-oxyl radical (TEMPO), undergoes
      oxidation and forms oxoammonium ion. Oxidized TEMPO oxidizes the alcohol and is
      simultaneously reduced to the N-OH form. The laccase then restores TEMPO back to
      the normal radical form and the oxidation cycle starts again. The role of TEMPO
      and the structures of its oxidized and reduced forms in the enzymatic oxidation
      process were clarified in collision-induced dissociation experiments and gas
      phase hydrogen/deuterium (H/D) exchange reactions. The amounts of enzyme and
      mediator were significant for product formation: with greater amounts
      overoxidation products, the corresponding benzoic acid and benzonitrile were
      formed. Smaller amounts of laccase and mediator generated benzaldehyde in high
      yield. The reaction pathway for benzonitrile formation is discussed and it is
      suggested to start from benzaldehyde and the ammonia in the ammonium acetate
      buffer.

PMID- 15468137
TI  - A streamlined approach to the analysis of volatile fatty acids and its
      application to the measurement of whole-body flux.
AB  - Volatile fatty acids (VFAs) are produced in the human colon by the bacterial
      breakdown of carbohydrates that escape digestion and absorption in the small
      intestine. They have important local and systemic effects on gastrointestinal and
      nutritional functions. Measuring their production is difficult because of
      inaccessibility of sampling sites and low circulating concentrations. Stable
      isotope tracer techniques are a way to measure VFA production but require
      measurement of isotope dilution in blood and other biological fluids. We have
      developed a streamlined and robust method to measure the concentration and
      enrichment of [(2)H]-labelled VFAs by gas chromatography/mass spectrometry
      (GC/MS) and [(13)C]-labelled VFAs by gas chromatography/combustion/isotope ratio
      mass spectrometry (GC/C/IRMS). Both types of analysis were carried out on the
      same samples allowing multiple tracer studies to be conducted. Good accuracy and
      repeatability were found for GC/MS analysis of [(2)H]-labelled VFAs. Careful
      handling of the background contribution, especially acetate, allowed quantitation
      of concentration and enrichment within the analysis. GC/C/IRMS analysis of
      [(13)C] VFAs was also achieved with good accuracy and repeatability. This
      methodology was used to determine whole-body acetate production in two subjects
      using multiple tracers ([(2)H(3)]- and [1-(13)C]acetate) and blood and urine
      sampling. Whole-body acetate flux was similar when measured either with [(2)H(3)]
      or [1-(13)C]acetate, and when flux was determined from plasma or urine tracer
      enrichment. This new method will permit rapid and accurate measurement of VFA
      flux using [(2)H]- and/or [(13)C]-labelled VFAs as tracers. Measurements of the
      contribution of colonic VFA production to whole-body VFA flux are now possible.

PMID- 15468138
TI  - Improved detection of amyloid in fat pad aspiration: an evaluation of Congo red
      stain by fluorescent microscopy.
AB  - Amyloid fat pad aspiration specimens for cases with a clinical suspicion of
      amyloid typically are stained with Congo red and examined by brightfield
      microscopy. Congophilia with apple-green birefringence by polarization microscopy
      (PM) is considered diagnostic for amyloid. Examination of Congo red-stained
      slides by fluorescent microscopy (FM) is considered by some to be a more
      sensitive detection method. In this study, we assessed the utility of this
      technique in cytopathology archival slides from abdominal fat pad aspirations
      previously stained with Congo red dye. Seventy-eight cases of abdominal fat pad
      aspirations collected during the last 5 yr and stained with the Congo red
      procedure were obtained from archival files. Additionally, 20 adipose tissue
      material slides prepared from the surgical pathology specimens were examined as
      controls. One representative smear was examined in each case using FM equipped
      with rhodamine excitation/absorption (540/570 nm) filters. Relevant clinical
      information was obtained in all cases. Twelve cases (15.4%) of the 78 fat pad
      aspiration cases were reported originally as positive by Congo red stain using
      polarization and apple-green birefringence as diagnostic criteria. On review,
      four cases were deemed unsatisfactory. By FM examination 29 of the 74 (39.2%)
      cases were reclassified as positive for amyloid. The results were confirmed by
      immunohistochemical stain for amyloid P protein and electron microscopy. A number
      of similar distinct fluorescence and immunohistochemical patterns were recognized
      in the positive cases. Minimally weak fluorescence in the adipose tissue was
      observed in the control cases. The use of FM in Congo red-stained fat pad smears
      can improve the detection of amyloid in cytology preparations.

PMID- 15468139
TI  - Follow-up findings on aspiration cytology of amyloid from vitreous fluid.

PMID- 15468140
TI  - Scyllo-inositol in normal aging human brain: 1H magnetic resonance spectroscopy
      study at 4 Tesla.
AB  - The scyllo-inositol and myo-inositol concentrations of 24 normal human subjects
      were measured in vivo using 1H magnetic resonance spectroscopy at 4 T. Single
      voxel short-echo (TE = 15 ms) metabolite spectra were collected from the white
      matter region of the corona radiata. Test-retest studies performed on 10 normal
      subjects demonstrated coefficient of variation for scyllo-inositol measurement of
      37%, compared with 6% for N-acetyl aspartate. Comparisons between old and young
      subjects showed higher concentration of scyllo-inositol and myo-inositol in older
      subjects and a trend for a correlation between scyllo-inositol and myo-inositol
      levels across subjects.

PMID- 15468141
TI  - Liquid chromatography/tandem mass spectrometry of unusual phenols from Yucca
      schidigera bark: comparison with other analytical techniques.
AB  - Qualitative and quantitative analyses of phenolic compounds are of interest for
      both medicinal and food plants. In the present work, the phenolic fraction from
      Yucca schidigera, a plant bearing the GRAS (Generally Recognized as Safe) label
      approved by the US Food and Drug Administration, was studied. Crude extracts of
      Y. schidigera bark were investigated by liquid chromatography/UV
      spectrophotometry with diode-array detection, liquid chromatography/electrospray
      ionization mass spectrometry (LC/ESI-MS) and liquid chromatography/electrospray
      ionization tandem mass spectrometry (LC/ESI-MS/MS), in order to develop and
      optimize simple and rapid techniques to determine both stilbenes and yuccaols for
      the purposes of quality control of collected material. With optimal LC and MS
      conditions, stilbenes and yuccaols were quantified with all the proposed methods
      and the results were compared. Sensitivity was evaluated and the results
      indicated that MS/MS detection in the multiple reaction monitoring mode is easily
      applicable to this plant and allows the rapid and direct identification and
      quantification of these peculiar compounds in crude plant extracts.

PMID- 15468142
TI  - The development of descriptors for solids: teaching "catalytic intuition" to a
      computer.

PMID- 15468143
TI  - Rapid determination of amino acids in neonatal blood samples based on
      derivatization with isobutyl chloroformate followed by solid-phase
      microextraction and gas chromatography/mass spectrometry.
AB  - The purpose of this study was to develop a simple, rapid and sensitive analytical
      method for determination of amino acids in neonatal blood samples. The developed
      method involves the employment of derivatization and a solid-phase
      microextraction (SPME) technique together with gas chromatography/mass
      spectrometry (GC/MS). Amino acids in blood samples were derivatized by a mixture
      of isobutyl chloroformate, methanol and pyridine, and the N(O,S)-alkoxycarbonyl
      alkyl esters thus formed were headspace extracted by a SPME fiber. Finally, the
      extracted analytes on the fiber were desorbed and detected by GC/MS in electron
      impact (EI) mode. L-Valine, L-leucine, L-isoleucine, L-phenylanaline and L
      tyrosine in blood samples were quantitatively analyzed by measurement of the
      corresponding N(O,S)-alkoxycarbonyl alkyl esters using an external standard
      method. SPME conditions were optimized, and the method was validated. The method
      was applied to diagnosis of neonatal phenylkenuria (PKU) and maple syrup urine
      disease (MSUD) by the analyses of five amino acids in blood samples. The results
      showed that the proposed method is a potentially powerful tool for simultaneous
      screening for neonatal PKU and MSUD.

PMID- 15468144
TI  - Tissue and fixative dependent shifts of delta13C and delta15N in preserved
      ecological material.
AB  - Carbon and nitrogen stable isotope analyses are routinely used to investigate
      aquatic food webs, and have potential application in retrospective investigations
      using archived materials. However, such analyses assume that storage does not
      alter isotopic signatures of materials preserved, or that changes in isotopic
      composition during storage are predictable. Here we examine preservation shifts
      on cod (Gadus morhua) muscle, roe and liver tissue over 21 months following
      preservation in 80% ethanol, in 4% formaldehyde, and by freezing. Preservation
      shifts were not consistent among tissues. High protein tissues exhibited greater
      delta(15)N shifts than low protein tissues in 4% formaldehyde, while greater
      delta(13)C shifts occurred in relatively higher fat tissues when preserved in
      alcohol. Freezing did not change isotopic signatures. Responses of delta(15)N and
      delta(13)C are explained by differences in the preservative's isotopic signature
      and the reaction properties and biochemical composition of the tissues preserved.
      The results clarify some of the processes that lead to isotopic change during
      preservation.

PMID- 15468145
TI  - Quantitative analysis of the P-glycoprotein inhibitor Elacridar (GF120918) in
      human and dog plasma using liquid chromatography with tandem mass spectrometric
      detection.
AB  - A liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method for the
      determination of the P-glycoprotein and breast cancer resistance protein
      inhibitor Elacridar in human and dog plasma is described. The internal standard
      was stable isotopically labelled Elacridar. Sample pretreatment involved liquid
      liquid extraction with tert-butyl methyl ether. Analysis of Elacridar and
      internal standard was performed by reversed-phase LC on a basic stable minibore
      analytical column with an eluent consisting of acetonitrile and aqueous ammonia.
      An API-2000 triple-quadrupole mass spectrometer with an electrospray ion source
      was used in the positive-ion multiple reaction monitoring mode. The run time per
      sample was only 6 min. The method is sensitive and specific, with a dynamic range
      from 1 to 500 ng ml(-1) from 100 microl of human or dog plasma. The accuracy of
      the method was within 15% bias and the precision was lower than 15% for all
      tested concentration levels and in both matrices. The method is simple and the
      liquid-liquid extraction produces clean samples. This method was successfully
      applied to support the pharmacokinetics of a clinical trial in which orally
      applied Elacridar was used as a bioavailability enhancer.

PMID- 15468146
TI  - Mass spectrometric studies on the intrinsic stability of destruxin E from
      Metarhizium anisopliae.
AB  - Destruxins are of current interest as bioactive agents. They are cyclic
      hexadepsipeptides produced by fungi, the most common destruxins, A, B and E,
      differing in the structure of a side chain. Before they can be widely used, the
      potential risk of destruxins and their metabolites entering the human food chain
      must to be assessed; thus, knowledge of the structures of their degradation
      products is essential. Here we report a study aimed at identifying, by tandem
      mass spectrometry and accurate mass analysis, the products resulting from
      thermally and temporally induced degradation of destruxin E. The degradation
      products fell into two groups: those with relatively simple modifications of the
      side chain and those involving much more complex rearrangements. The structures
      of most of the degradation products were deduced from the MS data, with the major
      product being destruxin E diol: significantly, this compound had previously been
      reported to have only been produced as a metabolic product of enzyme action
      rather than as a simple degradation product as demonstrated here.

PMID- 15468147
TI  - Corticotropin-releasing hormone induces keratinocyte differentiation in the adult
      human epidermis.
AB  - Previously we documented that human epidermis exclusively expresses corticotropin
      releasing hormone receptor 1 (CRH-R1). To define the role of CRH in the
      epidermis, we investigated its effects on differentiation of normal human adult
      epidermal keratinocytes. Thus, CRH inhibited proliferation in a dose dependent
      fashion and significantly decreased Ki-67 antigen expression. This effect was
      independent of either the presence or the absence of growth factors in the
      medium. Flow cytometry analysis demonstrated that CRH inhibited the transition
      from G0/1 to S phase of the cell cycle, which was accompanied by an increased
      expression of cdk inhibitor p16 (Ink4a) protein. The antiproliferative effect was
      attenuated by protein kinase C inhibitor (GF109203X) but not by H89 (protein
      kinase A inhibitor), PD98059, or SB203580 (MAP kinase inhibitors). The cell cycle
      withdrawal was associated with the induction of keratinocyte differentiation.
      Thus, CRH stimulated the expression of cytokeratin 1 and involucrin, and
      inhibited cytokeratin 14 on both mRNA and protein levels. It also increased cell
      granularity and cell size. Furthermore, CRH induced signal transduction cascade
      that included stimulation of inositol 1,4,5-triphosphate, which was time and dose
      dependent. CRH also increased activator protein-1 DNA binding activity with JunD
      identified as the most important element. Thus, activation of CRH-R1 induces a
      non-random and sequential signal transduction cascade governing both keratinocyte
      differentiation and the inhibition of cell proliferation through G0/1 arrest. We
      propose that this program, triggered by CRH interaction with CRH-R1, includes
      induction of a transduction pathway involving the sequential activation of
      phospholipase C, protein kinase C, activator protein-1 (including Jun D), and
      p16.

PMID- 15468148
TI  - Calcium pump disorders of the skin.
AB  - The causes of Darier disease (DD) and Hailey-Hailey disease (HHD) have eluded
      clinicians and scientists for more than 60 years. DD is characterized by loss of
      adhesion between suprabasal epidermal cells associated with abnormal
      keratinization, while loss of epidermal cell-to-cell adhesion is predominant in
      HHD. The genes for both conditions have recently been identified using candidate
      positional cloning approaches. The gene for DD (ATP2A2) encodes a calcium
      transport ATPase of the sarco (endo)plasmic reticulum (SERCA2) Verboomen et al.
      [1992: Biochem J 286(Pt 2):591-595], while the gene for HHD (ATP2C1) codes for a
      secretory pathway for calcium and manganese transport ATPase of the Golgi
      apparatus (SPCA1) Hu et al. [2000: Nat Genet 24:61-65]. These results have
      provided completely new insights into the role of calcium and/or manganese in
      maintaining skin integrity. Although the precise disease mechanisms remain to be
      understood, these discoveries open a new field in research for the understanding
      and the treatment of these distressing disorders.

PMID- 15468149
TI  - Molecular genetics of hereditary hair and nail disease.
AB  - Hair and nail development have many similarities and are likely to share many
      developmental pathways. This is evident from the ectodermal dysplasias that
      affect both appendages. Of special interest are syndromic disorders as they show
      the effects of disturbances in molecular pathways that are essential for normal
      embryonic development. In this review, recent results from studies of syndrome
      affecting hair and nail development will be discussed.

PMID- 15468150
TI  - Genetic diseases of the skin: progress and perspectives.

PMID- 15468151
TI  - Gene therapy and the skin.
AB  - Significant progress has been made during the past decade in corrective gene
      therapy of the skin. This includes advances in vector technology, targeted gene
      expression, gene replacement, gene correction, and the availability of
      appropriate animal models for a variety of candidate diseases. While non-viral
      integration of large genes such as essential basement membrane proteins has been
      mastered, new challenges such as the control of immune responses lie ahead of the
      research community. Among the first skin diseases, patients with junctional
      epidermolysis bullosa (JEB) and xeroderma pigmentosum (XP) will enter clinical
      trials.

PMID- 15468152
TI  - Progress in epidermolysis bullosa: genetic classification and clinical
      implications.
AB  - Epidermolysis bullosa (EB), a heterogenous group of genodermatoses, is
      characterized by fragility and blistering of the skin associated with
      extracutaneous manifestations. Based on clinical severity, constellation of the
      phenotypic manifestations, and the level of tissue separation within the
      cutaneous basement membrane zone (BMZ), EB has been divided into distinct
      subcategories. Traditionally, these include the simplex, junctional, and
      dystrophic forms of EB, and recently attention has been drawn to hemidesmosomal
      variants demonstrating tissue separation at the level of the hemidesmosomes.
      Specific mutations in ten distinct genes expressed within the cutaneous BMZ have
      been delineated in >500 families with different variants of EB. The types of
      mutations, their positions along the affected genes, and their consequences at
      the mRNA and protein levels provide explanation for the phenotypic variability
      and genetic heterogeneity of this group of genodermatoses. Elucidation of
      mutations in different forms of EB has direct translational applications for
      improved diagnosis and molecularly based classification with prognostic
      implications as well as for genetic counseling and DNA-based prenatal testing in
      families with EB.

PMID- 15468153
TI  - Ectodermal dysplasias.
AB  - Ectodermal dysplasias are a large group of heritable conditions characterized by
      congenital defects of one or more ectodermal structures and their appendages:
      hair (hypotrichosis, partial, or total alopecia), nails (dystrophic,
      hypertrophic, abnormally keratinized), teeth (enamel defect or absent), and sweat
      glands (hypoplastic or aplastic). The ectodermal dysplasias, as a rule, are not
      pure "one-layer diseases." Mesodermal and, rarely, endodermal dysplasias coexist.
      Embryogenesis exhibits distinct tissue organizational fields and specific
      interactions among the germ layers that may lead to a wide range of ectodermal
      dysplasias when genes important for development are mutated or otherwise altered
      in expression. Of the approximately 200 different ectodermal dysplasias, about 30
      have been studied at the molecular level with identification of the causative
      gene. Freire-Maia and Pinheiro used the clinical aspects for their
      classification, and Priolo integrated molecular genetic and clinical aspects for
      her scheme. Those two more historical classification schemes have the difficulty
      that, when applied strictly, several additional groups of diseases should be
      integrated within the term "ectodermal dysplasias," e.g. keratodermas with skin
      or hair alterations or the ichthyoses with associated features. Such consequent
      classification would lead to an endless list of diseases and would be useless for
      the practical work. Recent evidence implicates a genetic defect in different
      pathways orchestrating ectodermal organogenesis. Modern molecular genetics will
      increasingly elucidate the basic defects of the different syndromes and yield
      more insight into the regulatory mechanisms of embryology. In this way, a
      reclassification of ectodermal dysplasias will be possible according to the
      function of their involved mutated genes. Lamartine recently proposed a helpful
      classification according to the functions of the genes discovered in different
      types of ectodermal dysplasias. Accordingly, the present overview categorizes the
      various ectodermal dysplasias into four major functional subgroups: cell-cell
      communication and signaling, adhesion, transcription regulation, and development.

PMID- 15468154
TI  - Neural connectivity in hand sensorimotor brain areas: an evaluation by evoked
      field morphology.
AB  - The connectivity pattern of the neural network devoted to sensory processing
      depends on the timing of relay recruitment from receptors to cortical areas. The
      aim of the present work was to uncover and quantify the way the cortical relay
      recruitment is reflected in the shape of the brain-evoked responses. We recorded
      the magnetic somatosensory evoked fields (SEF) generated in 36 volunteers by
      separate bilateral electrical stimulation of median nerve, thumb, and little
      fingers. After defining an index that quantifies the shape similarity of two SEF
      traces, we studied the morphologic characteristics of the recorded SEFs within
      the 20-ms time window that followed the impulse arrival at the primary sensory
      cortex. Based on our similarity criterion, the shape of the SEFs obtained
      stimulating the median nerve was observed to be more similar to the one obtained
      from the thumb (same median nerve innervation) than to the one obtained from the
      little finger (ulnar nerve innervation). In addition, SEF shapes associated with
      different brain regions were more similar within an individual than between
      subjects. Because the SEF morphologic characteristics turned out to be quite
      diverse among subjects, we defined similarity levels that allowed us to identify
      three main classes of SEF shapes in normalcy. We show evidence that the
      morphology of the evoked response describes the anatomo-functional connectivity
      pattern in the primary sensory areas. Our findings suggest the possible existence
      of a thalamo-cortico-thalamic responsiveness loop related to the different
      classes.

PMID- 15468155
TI  - Functional principal component analysis of fMRI data.
AB  - We describe a principal component analysis (PCA) method for functional magnetic
      resonance imaging (fMRI) data based on functional data analysis, an advanced
      nonparametric approach. The data delivered by the fMRI scans are viewed as
      continuous functions of time sampled at the interscan interval and subject to
      observational noise, and are used accordingly to estimate an image in which
      smooth functions replace the voxels. The techniques of functional data analysis
      are used to carry out PCA directly on these functions. We show that functional
      PCA is more effective than is its ordinary counterpart in recovering the signal
      of interest, even if limited or no prior knowledge of the form of hemodynamic
      function or the structure of the experimental design is specified. We discuss the
      rationale and advantages of the proposed approach relative to other exploratory
      methods, such as clustering or independent component analysis, as well as the
      differences from methods based on expanded design matrices.

PMID- 15468156
TI  - The study of cytopathological aspects induced by human cytomegalovirus infection.
AB  - In cytological examination, human cytomegalovirus (HCMV) infection can not be
      implied unless typical HCMV-infected cells like owl's-eye cells are present.
      However, such cells are not always observed in HCMV-infection cases. The aim of
      our study is to establish the cytopathological features induced by HCMV. In vitro
      transfection and fluorescence in situ hybridization (FISH) were performed on
      human embryo lung (HEL) cells. Marked cellular aggregation was observed at 6-hr
      postinfection (hpi). Multinucleated cells, giant cells, and, particularly, small
      vacuoles were present in the nuclei or cytoplasm before the appearance of
      inclusion bodies. However, molding and ground glass in nuclei were absent. Cell
      clusters displayed round cytoplasm, dispersed later, and showed anisocytosis. All
      features occurred before 48 hpi when the owl's-eye cell appeared. In FISH, the
      positive signal highlighted viral particles that became predominant and localized
      in nuclei. These cytological aspects are dependent on viral replication and
      contribute to the cytological detection of HCMV infection.

PMID- 15468157
TI  - Diagnostic protein discovery using proteolytic peptide targeting and
      identification.
AB  - Plasma protein profiling with mass spectrometry is currently being evaluated as a
      diagnostic tool for cancer and other diseases. These experiments consist of three
      steps: plasma protein fractionation, analysis with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), and
      comparisons of the MALDI profiles to develop diagnostic fingerprints using
      bioinformatic techniques. While preliminary results appear promising in small
      sample groups, the method is limited by the sensitivity of MALDI-MS for intact
      proteins, the limited mass range of MALDI-MS, and difficulties associated with
      isolating individual proteins for identification to validate the diagnostic
      fingerprint. Here we present an alternative and improved method directed toward
      diagnostic protein discovery, which incorporates proteolytic peptide profiling,
      bioinformatic targeting of ion signals, and MALDI tandem mass spectrometry
      (MS/MS) peptide sequencing, rather than fingerprinting. Pancreatic cancer
      patients, pancreatitis patients, and controls are used as the model system.
      Profiling peptides after enzymatic digestion improves sensitivity and extends the
      accessible protein molecular weight range when compared to intact protein
      profiling. The first step is to extract and fractionate the proteins from plasma.
      Each fraction is digested with trypsin and subsequently analyzed by MALDI-MS.
      Rather than using bioinformatic analysis as a pattern-matching technique,
      peptides are targeted based on the disease to control peak intensity ratios
      measured in the averages of all mass spectra in each group and t-tests of the
      intensity of each individual peak. The targeted peptide ion signals are
      subsequently identified using MALDI-MS/MS in quadrupole-TOF and tandem-TOF
      instruments. This study found not only the proteins targeted and identified by a
      previous protein profiling experiment, but also detected additional proteins.
      These initial results are consistent with the known biology of pancreatic cancer
      or pancreatitis, but are not specific to those diseases.

PMID- 15468158
TI  - The use of liquid chromatography/mass spectrometry for quantitative analysis of
      oxycodone, oxymorphone and noroxycodone in Ringer solution, rat plasma and rat
      brain tissue.
AB  - Sensitive and reproducible methods for the determination of oxycodone,
      oxymorphone and noroxycodone in Ringer solution, rat plasma and rat brain tissue
      by liquid chromatography/mass spectrometry are described. Deuterated analogs of
      the substances were used as internal standards. Samples in Ringer solution were
      analyzed by direct injection of 10 microL Ringer solution diluted by an equal
      volume of water. The limit of quantification was 0.5 ng/mL and the method was
      linear in the range of 0.5-150 ng/mL for all substances. To analyze oxycodone and
      oxymorphone in rat plasma, 50 microL of plasma were precipitated with
      acetonitrile, and the supernatant was directly injected onto the column. To
      analyze oxycodone, oxymorphone and noroxycodone in rat plasma, 100 microL of rat
      plasma were subjected to a C18 solid-phase extraction (SPE) procedure, before
      reconstituting in mobile phase and injection onto the column. For both methods
      the limit of quantification in rat plasma was 0.5 ng/mL and the methods were
      linear in the range of 0.5-250 ng/mL for all substances. To analyze the content
      of oxycodone, oxymorphone and noroxycodone in rat brain tissue, 100 microL of the
      brain homogenate supernatant were subjected to a C18 SPE procedure. The limit of
      quantification of oxycodone was 20 ng/g brain, and for oxymorphone and
      noroxycodone 4 ng/g brain, and the method was linear in the range of 20-1000 ng/g
      brain for oxycodone and 4-1000 ng/g brain for oxymorphone and noroxycodone. All
      methods utilized a mobile phase of 5 mM ammonium acetate in 45% acetonitrile, and
      a SB-CN column was used for separation. The total run time of all methods was 9
      min. The intra-day precision and accuracy were <11.3% and <+/-14.9%,
      respectively, and the inter-day precision and accuracy were <14.9% and <+/-6.5%,
      respectively, for all the concentrations and matrices described.

PMID- 15468159
TI  - Development, validation and transfer of a hydrophilic interaction liquid
      chromatography/tandem mass spectrometric method for the analysis of the tobacco
      specific nitrosamine metabolite NNAL in human plasma at low picogram per
      milliliter concentrations.
AB  - A highly sensitive bioanalytical method based on a simple liquid/liquid
      extraction and hydrophilic interaction liquid chromatography with tandem mass
      spectrometry (HILIC/MS/MS) analysis has been developed, validated and transferred
      for the determination of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a
      tobacco-specific nitrosamine metabolite. Deuterated NNAL (NNAL-d(4)) was
      synthesized and used as the internal standard. This method can be used for the
      analysis of free and total NNAL (free NNAL plus NNAL-gluc) in K(3)-EDTA human
      plasma. Free NNAL and NNAL-d(4) are extracted from human plasma by liquid/liquid
      extraction. To analyze for total NNAL and the internal standard, a separate
      aliquot of the K(3)-EDTA human plasma is treated with beta-glucuronidase to
      deconjugate the NNAL-gluc; the total NNAL and internal standard are then
      extracted using liquid/liquid extraction. After drying down under nitrogen, the
      residue is reconstituted with acetonitrile and analyzed using positive ion
      electrospray and HILIC/MS/MS at a flow rate of 1.0 mL/min. The chromatographic
      run time is 1.0 min per injection, with retention time for both NNAL and NNAL
      d(4) of 0.75 min with a capacity factor (k') of 2. The standard curve range for
      this assay is from 5.00-1000 pg/mL for both free and total NNAL, using a total
      plasma sample volume of 1.0 mL. The interday precision and accuracy of the
      quality control (QC) samples demonstrated <7.6% relative standard deviation (RSD)
      and <3.3% relative error (RE) for free NNAL. For total NNAL, the interday
      precision and accuracy of the QC samples demonstrated <11.7% RSD and <2.8% RE.
      Optimization of enzyme hydrolysis of NNAL-gluc is discussed in detail. The
      overall recoveries for free and total NNAL and IS were 68.2 and 71.5% (free) and
      70.7 and 65.5% (total). No adverse matrix effects were noticed for this assay.

PMID- 15468161
TI  - Complete sequences of small acid-soluble proteins from Bacillus globigii.
AB  - Three abundant small acid-soluble proteins (SASPs) from spores of Bacillus
      globigii were sequenced using matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry with post-source decay and nanoelectrospray collision
      induced dissociation tandem mass spectrometry. The proteins were extracted from
      spores with 1 M HCl. Scanning electron micrographs of spores before and after
      acid extraction show that the spores retain their overall structure but have a
      shriveled texture following the acid treatment. Extracted SASPs were purified by
      high-performance liquid chromatography and molecular masses of the SASPs were
      identified at 7068 (SASP-1), 7332 (SASP-2), and 8889 (gamma-SASP). De novo
      peptide sequencing was used to determine the protein sequences. The correct
      ordering of peptide sequences was aided by mapping overlapping enzymatic digests
      and by comparison with homologous SASPs from Bacillus stearothermophilus. B.
      globigii is used in many field tests as a surrogate for B. anthracis. Thus
      complete SASP sequences from B. globigii will facilitate the development of
      methods for rapid identification of bacteria based on mass spectrometry and the
      examination of taxonomic relationships between Bacillus species.

PMID- 15468162
TI  - Over-expression of the p110beta but not p110alpha isoform of PI 3-kinase inhibits
      motility in breast cancer cells.
AB  - Phosphoinositide 3-kinase (PI 3-kinase) activity is required for growth factor
      induced cytoskeletal regulation and cell migration. We previously found that in
      MTLn3 rat adenocarcinoma cells, EGF-stimulated induction of actin barbed ends and
      lamellipod extension specifically requires the p85/p110alpha isoform of PI 3
      kinase. To further characterize signaling by distinct PI 3-kinase isoforms, we
      have developed MTLn3 cells that transiently or stably overexpress either
      p110alpha or p110beta. Transient overexpression of p110beta inhibited EGF
      stimulated lamellipod extension, whereas p110alpha-transfected cells showed
      normal EGF-stimulated lamellipod extension. Similar results were obtained by
      overexpression of kinase-dead p110beta, suggesting that effects on cytoskeletal
      signaling were due to competition with p85/p110alpha complexes. Stable
      overexpression of p110alpha appeared to be toxic, based on the difficulty in
      obtaining stable overexpressing clones. In contrast, cells expressing a 2-fold
      increase in p110beta were readily obtainable. Interestingly, cells stably
      expressing p110beta showed a marked inhibition of EGF-stimulated lamellipod
      extension. Using computer-assisted analysis of time-lapse images, we found that
      overexpression of p110beta caused a nearly complete inhibition of motility. Cells
      overexpressing p110beta showed normal activation of Akt and Erk, suggesting that
      overall PI 3-kinase signaling was intact. A chimeric p110 molecule containing the
      p85-binding and Ras-binding domains of p110alpha and the C2, helical, and kinase
      domains of p110beta, was catalytically active yet also inhibited EGF-stimulated
      lamellipod extension. These data highlight the differential signaling by distinct
      p110 isoforms. Identification of effectors that are differently regulated by
      p110alpha versus p110beta will be important for understanding cell migration and
      its role in metastasis.

PMID- 15468163
TI  - Rho expression and activation in vascular smooth muscle cells.
AB  - Phenotypic modulation of smooth muscle cells (SMC) involves dramatic changes in
      expression and organization of contractile and cytoskeletal proteins, but little
      is known of how this process is regulated. The present study used a cell culture
      model to investigate the possible involvement of RhoA, a known regulator of the
      actin cytoskeleton. In rabbit aortic SMC seeded into primary culture at moderate
      density, Rho activation was high at two functionally distinct time-points, first
      as cells modulated to the "synthetic" phenotype, and again upon confluence and
      return to the "contractile" phenotype. Rho expression increased with time, such
      that maximal expression occurred upon return to the contractile state. Transient
      transfection of synthetic state cells with constitutively active RhoA (Val14RhoA)
      caused a reduction in cell size and reorganization of cytoskeletal proteins to
      resemble that of the contractile phenotype. Actin and myosin filaments were
      tightly packed and highly organised while vimentin localised to the perinuclear
      region; focal adhesions were enlarged and concentrated at the cell periphery.
      Conversely, inhibition of endogenous Rho by C3 exoenzyme resulted in complete
      loss of contractile filaments without affecting vimentin distribution; focal
      adhesions were reduced in size and number. Treatment of synthetic state SMC with
      known regulators of SMC phenotype, heparin and thrombin, caused a modest increase
      in Rho activation. Long-term confluence and serum deprivation induced cells to
      return to a more contractile phenotype and this was augmented by heparin and
      thrombin. The results implicate RhoA for a role in regulating SMC phenotype and
      further show that activation of Rho by heparin and thrombin correlates with the
      ability of these factors to promote the contractile phenotype.

PMID- 15468164
TI  - Disruption of genes encoding predicted inner arm dynein heavy chains causes
      motility phenotypes in Tetrahymena.
AB  - The multi-dynein hypothesis [Asai, 1995: Cell Motil Cytoskeleton 32:129-132]
      states: (1) there are many different dynein HC isoforms; (2) each isoform is
      encoded by a different gene; (3) different isoforms have different functions.
      Many studies provide evidence in support of the first two statements [Piperno et
      al., 1990: J Cell Biol 110:379-389; Kagami and Kamiya, 1992: J Cell Sci 103:653
      664; Gibbons, 1995: Cell Motil Cytoskeleton 32:136-144; Porter et al., 1996:
      Genetics 144:569-585; Xu et al., 1999: J Eukaryot Microbiol 46:606-611] and there
      is evidence that outer arms and inner arms play different roles in flagellar
      beating [Brokaw and Kamiya, 1987: Cell Motil. Cytoskeleton 8:68-75]. However,
      there are few studies rigorously testing in vivo whether inner arm dyneins,
      especially the 1-headed inner arm dyneins, play unique roles. This study tested
      the third tenet of the multi-dynein hypothesis by introducing mutations into
      three inner arm dynein HC genes (DYH8, 9 and 12) that are thought to encode HCs
      associated with 1-headed inner arm dyneins. Southern blots, Northern blots, and
      RT-PCR analyses indicate that all three mutants (KO-8, 9, and 12) are complete
      knockouts. Each mutant swims slower than the wild-type cells. The beat frequency
      of KO-8 cells is lower than that of the wild-type cells while the beat
      frequencies of KO-9 and KO-12 are not different from that of wild-type cells. Our
      results suggest that each inner arm dynein HC is essential for normal cell
      motility and cannot be replaced functionally by other dynein HCs and that not all
      of the 1-headed inner arm dyneins play the same role in ciliary motility. Thus,
      the results of our study support the multi-dynein hypothesis [Asai, 1995: Cell
      Motil Cytoskeleton 32:129-132].

PMID- 15468165
TI  - Vasoactive intestinal peptide induces neuroendocrine differentiation in the LNCaP
      prostate cancer cell line through PKA, ERK, and PI3K.
AB  - BACKGROUND: Neuroendocrine (NE) differentiation in prostate cancer has been
      correlated with unfavorable clinical outcome. The mechanisms by which prostate
      cancer acquires NE properties are poorly understood, but several signaling
      pathways have been proposed. We have previously observed that vasoactive
      intestinal peptide (VIP) stimulates cAMP production mainly through VPAC(1)
      receptor, inducing NE differentiation in LNCaP cells. The aim of this study was
      to analyze the mechanisms involved in this process. METHODS: Reverse
      transcriptase (RT)-polymerase chain reaction (PCR), quantitative real-time RT
      PCR, Western blotting, and immunocytochemistry were performed. RESULTS: LNCaP
      cells produce VIP, as demonstrated by RT-PCR and immunocytochemistry. VIP induced
      NE differentiation of LNCaP cells at a time as short as 1 hr of treatment, and
      the same occurred with the expression and secretion of neuronal-specific enolase
      (NSE, a NE differentiation marker). These effects were faster than those exerted
      by serum-deprivation. VIP induced extracellular signal-regulated kinase 1 and 2
      (ERK1/2) phosphorylation and NE differentiation by PKA-dependent and independent
      pathways, since the PKA inhibitor H89 partially blocked VIP-induced NE
      differentiation and did not affect ERK1/2 phosphorylation. mitogen-activated
      protein kinase kinase (MEK) and phosphoinositide 3-kinase (PI3K) appear to be
      also involved since the inhibitors PD98059 and wortmannin abolished ERK1/2
      phosphorylation and decreased NE differentiation induced by VIP. Moreover, VIP
      activated Ras suggesting the involvement of a Ras-dependent pathway. CONCLUSIONS:
      VIP behaves as autocrine/paracrine factor in LNCaP cells by inducing NE
      differentiation through PKA, ERK1/2, and PI3K.

PMID- 15468166
TI  - Effectiveness of adjuvant intermittent endocrine therapy following neoadjuvant
      endocrine therapy and external beam radiation therapy in men with locally
      advanced prostate cancer.
AB  - PURPOSE: To clarify the optimal duration and methods for adjuvant endocrine
      therapy after external beam radiation therapy (EBRT) in patients with locally
      advanced prostate cancer. MATERIALS AND METHODS: Between 2001 and 2003, 215
      patients with locally advanced prostate cancer were enrolled in the study.
      Patients were registered as primary candidates of the study and were treated with
      6 months of LHRH agonist, with short-term of antiandrogen treatment for flare-up
      prevention. Patients with PSA levels below 10 ng/ml after the 6-month endocrine
      treatment were randomly divided into two arms. Then, a total dose of 72 Gy was
      given to the prostate. After 14 months of the protocol treatment, patients were
      treated with continuous androgen ablation (arm 1) or intermittent androgen
      ablation (arm 2). RESULTS: A total of 188 cases (87%) remained in the protocol.
      The median PSA level at entry was 25.3 ng/ml. The Gleason score was 2-6 in 32
      cases (16%), 7 in 94 cases (48%), and 8-10 in 68 cases (35%). The median PSA
      level showed a remarkable decrease to 1.1, 0.2, and 0.1 ng/ml, after 6, 8, and 14
      months of the protocol treatment, respectively. Of the 157 cases treated with
      EBRT, 153 cases (97.5%) had no biochemical failure in the mean follow-up of 17.3
      months. CONCLUSIONS: The present study may reveal the possibilities of
      intermittent endocrine therapy after EBRT. However, the follow-up interval is
      short and little can be said about the results observed so far, exception of
      acute tolerance and patient acceptance of the protocol.

PMID- 15468167
TI  - Beta3 integrins facilitate matrix interactions during transendothelial migration
      of PC3 prostate tumor cells.
AB  - BACKGROUND: beta3 integrins play a role in metastatic progression of prostate
      cancer by mediating adhesion of cancer cells to endothelium and migration through
      extracellular matrix (ECM). However, the role of beta3 integrins during
      transendothelial migration (TEM) of prostate tumor cells is poorly understood. We
      examined the role of beta3 integrins in TEM of PC3 human prostate cancer cells
      through a monolayer of human lung microvascular endothelial cells (HLMVECs).
      METHODS: PC3 cells were challenged with beta3 integrin antibodies or antisense
      nucleotides and their efficiency to migrate through monolayers of endothelial
      cells (ECs) was assessed using confocal microscopy. RESULTS: beta3 integrins in
      PC3 cells are not localized in focal contacts and their blockade significantly
      inhibited TEM by over 50% preferentially during late stages of migration.
      Formation of PC3 cell pseudopodia on matrigel was significantly reduced by beta3
      integrin antisense oligonucleotides. CONCLUSIONS: beta3 integrins play important
      roles during TEM of PC3 cells while interacting with the matrix underneath the
      endothelium. These interactions are independent of the ability to cluster beta3
      integrins into focal adhesions.

PMID- 15468168
TI  - Explicit-chain model of native-state hydrogen exchange: implications for event
      ordering and cooperativity in protein folding.
AB  - Native-state hydrogen exchange experiments on several proteins have revealed
      partially unfolded conformations with diverse stabilities. These equilibrium
      observations have been used to support kinetic arguments that folding proceeds
      via a sequential "pathway." This interpretative logic is evaluated here by
      analyzing the relationship between thermodynamic behavior and folding kinetics in
      a class of simplified lattice protein models. The chain models studied have
      varying degrees of cooperative interplay (coupling) between local helical
      conformational preference and favorable nonlocal interactions. When model
      cooperativity is high, as native conditions are weakened, "isotherms" of free
      energy of exchange for residues belonging to the same helix merge together before
      global unfolding. The point of merger depends on the model energetic favorability
      of the helix. This trend is similar to the corresponding experimental
      observations. Kinetically, we find that the ordering of helix formation in the
      very last stage of native core assembly tends to follow the stabilities of their
      converged isotherms. In a majority (but not all) of folding trajectories, the
      final assembly of helices that are thermodynamically more stable against exchange
      precedes that of helices that are less stable against exchange. These model
      features are in partial agreement with common experimental interpretations.
      However, the model results also underscore the ensemble nature of the folding
      process: the kinetics of helix formation is not a discrete, strictly "all-or
      none" process as that envisioned by certain non-explicit-chain models. Helices
      generally undergo many cycles of partial formation and dissolution before their
      conformations are fixed in the final assembly stage of folding, a kinetic stage
      that takes up only approximately 2% of the average folding time in the present
      model; and the ordering of the helices' final assembly in some trajectories can
      be different from the dominant ordering stipulated by the exchange isotherms.

PMID- 15468169
TI  - Gap junction diseases of the skin.
AB  - Gap junctions are intercellular channels that allow the passage of water, ions,
      and small molecules. They are involved in quick, short-range messaging between
      cells and are found in skin, nervous tissue, heart, and muscle. An increasing
      number of hereditary skin disorders appear to be caused by mutations in one of
      the genes coding for the constituent proteins of gap junctions, known as
      connexins. In this review, the currently known connexin disorders that feature
      skin abnormalities are described: keratitis-ichthyosis deafness syndrome,
      erythrokeratoderma variabilis, Vohwinkel's syndrome, and a novel disorder called
      hypotrichosis-deafness syndrome. What is known about the pathogenesis of these
      disorders is discussed and related to gap junction physiology.

PMID- 15468170
TI  - The genetics of skin cancer.
AB  - Recent advances in molecular genetics have led to a better understanding of the
      biological underpinnings of skin cancer formation. As with most cancers, the RB,
      p53, and RAS pathways appear to play prominent roles in the pathogenesis of
      several skin cancer types. Although various components of these pathways may be
      differentially altered in squamous cell carcinoma (SCC), basal cell carcinoma
      (BCC), and cutaneous melanoma, the final biochemical expression of these defects
      may be the same. With the unraveling of these genetic mechanisms, a more targeted
      approach to diagnosis and treatment may be possible in the near future.

PMID- 15468171
TI  - Systemic administration of a soluble betaglycan suppresses tumor growth,
      angiogenesis, and matrix metalloproteinase-9 expression in a human xenograft
      model of prostate cancer.
AB  - BACKGROUND: Transforming growth factor beta (TGFbeta) over-expression in prostate
      cancer has been shown to promote tumor progression and neo-vascularization. In
      this study, we have investigated the efficacy and the potential mechanism of a
      TGFbeta antagonist, a recombinant soluble betaglycan (sBG), as a prostate cancer
      therapeutic agent after systemic administration in a xenograft model. METHODS:
      Recombinant sBG was delivered continuously via ALZET osmotic pumps or by daily
      bolus i.p. injection at 4.2 mg/kg/day for 14 days in human prostate cancer DU145
      xenograft bearing nude mice. Tumors were analyzed for their size, blood volume by
      hemoglobin assay, microvessel density (MVD) by CD-31 immunostaining, and
      apoptosis by TUNEL assay. Matrix metalloproteinase-9 (MMP-9) activity and
      expression in the DU145 conditioned media were determined by gelatin zymography
      and Western blotting, respectively. Tissue sections were stained with a
      polyclonal antibody to MMP-9 using an immuno-fluorescence method. RESULTS:
      Continuous or bolus administration of sBG showed a similar significant inhibition
      of DU145 xenograft growth associated with a reduced tumor blood volume and MVD,
      and an enhanced intra-tumoral apoptosis. Treatment with sBG inhibited both
      endogenous and TGFbeta-induced MMP-9 activity and expression in a dose-dependent
      manner in vitro and reduced in vivo MMP-9 expression in DU145 xenografts.
      CONCLUSIONS: Our results for the first time indicate that TGFbeta blockade by
      systemic sBG administration can inhibit DU145 prostate xenograft growth and
      angiogenesis. The inhibition is likely in part mediated by the attenuation of
      TGFbeta-induced MMP-9 expression.

PMID- 15468172
TI  - Establishment and characterization of a human primary prostate carcinoma cell
      line, HH870.
AB  - BACKGROUND: Development of new therapeutic modalities for human prostate
      carcinoma has been impeded by a lack of adequate in vitro and in vivo models.
      Most in vitro studies have been carried out using a limited number of human
      prostate cancer cell lines that are mostly derived from metastatic tumors sites
      or are immortalized. METHODS: Characterization of the prostate cancer cell line,
      HH870, included description of morphology, determination of doubling time,
      response to androgens, immunocytochemistry, and immunoblotting of proteins known
      to be associated with prostate carcinoma, karyotyping, fluorescence in situ
      hybridization (FISH), DNA profiling, and growth as xenograft in athymic rodents.
      RESULTS: HH870 expresses various epithelial marker antigens that correlate with
      known basic immunostaining profiles of prostate adenocarcinoma, although the cell
      line does not express PSA, PSMA, or PAP. HH870 exhibits complex chromosomal
      abnormalities and harbors no immortalizing HPV, BKV, JCV, and SV40 DNA.
      CONCLUSIONS: We report the successful establishment and characterization of a new
      long-term primary human prostate tumor cell line HH870.

PMID- 15468173
TI  - Characterization of a lymph node within the mouse prostate: Detailed analysis
      using whole mount histology.
AB  - BACKGROUND: Due to the prevalence of prostate disease, there is a growing
      interest in the immunobiology of the prostate and its contribution to such
      pathologies. Further study is needed to fully characterize immune responses
      within the prostate. METHODS: Mouse ventral prostates were removed and analyzed
      using conventional immunohistochemistry, or by a novel whole mount technique,
      which allows the visualization of complete structures within the prostate.
      RESULTS: A lymphoid structure was detected within the base of the mouse ventral
      prostate. Whole mount and cryostat sections revealed an organized arrangement of
      lymphocytes, along with dendritic cells interspersed throughout the node. It
      possessed a rich network of lymph node specific high endothelial venules (HEVs)
      and adjoining lymphatics containing immune cells. CONCLUSIONS: Our results
      demonstrate the presence of a lymphoid structure within the base of the mouse
      ventral prostate possessing traits characteristic of an organized peripheral
      lymph node.

PMID- 15468174
TI  - Astrocyte-specific overexpression of insulin-like growth factor-I promotes brain
      overgrowth and glial fibrillary acidic protein expression.
AB  - Insulin-like growth factor-I (IGF-I) is widely expressed in the central nervous
      system (CNS). Whereas during normal development IGF-I is expressed predominantly
      by neurons and to a much lesser degree by glial cells, its expression in
      astrocytes, and often in microglia, is increased during and/or after variety of
      CNS injuries. Recently we have generated a new line of IGF-I Tg mice, called IGF
      I(Ast/Tet-Off) Tg mice, in which IGF-I transgene is expressed specifically in
      astrocytes and is tightly controlled by the tetracycline analog doxycycline. In
      this study we examined whether IGF-I derived from astrocytes is capable of
      promoting neural cell growth during development. When the IGF-I transgene is
      allowed to be expressed, IGF-I(Ast/Tet-Off) Tg mice exhibit markedly increases in
      1) brain weight; 2) brain DNA and protein abundance; and 3) number of neurons,
      oligodendrocytes, and astrocytes, as well as myelination, findings similar to
      those observed in our other lines of Tg mice that express IGF-I transgene
      predominantly in neurons. Unlike Tg mice with neuron-specific IGF-I expression,
      which manifest marked increases in the concentrations of oligodendrocyte/myelin
      specific proteins, however, IGF-I(Ast/Tet-Off) Tg mice exhibit an increase in the
      concentration of glial fibrillary acidic protein, an astrocyte-specific protein.
      Furthermore, when transgene expression is blunted, brain overgrowth in IGF
      I(Ast/Tet-Off) Tg mice ceases. Our data indicate that astrocyte-derived IGF-I is
      capable of promoting neural cells growth in vivo. Our data also suggest that IGF
      I's actions in CNS depend in part on the location of its expression and cellular
      microenvironment and that continuous presence of IGF-I expression is necessary
      for brain overgrowth.

PMID- 15468175
TI  - Regeneration of the inner ear as a model of neural plasticity.
AB  - The publication of a paper entitled "Direct transdifferentiation gives rise to
      the earliest new hair cells in regenerating avian auditory epithelium" in the
      Journal of Neuroscience Research offers the opportunity to call attention to a
      well-developed line of research on the auditory receptor of birds, which should
      be of interest to students of regeneration and plasticity of the mature nervous
      system in higher vertebrates, including mammals. Although hair cell proliferation
      normally stops before hatching, destruction of the auditory receptors of the
      chicken may be followed by complete regeneration of hair cells. Most of the new
      hair cells arise from a new wave of proliferation, but Roberson et al. show that
      about one-third of the new hair cells are formed without undergoing cell division
      and thus may differentiate from so-called supporting cells or cells with an
      "intermediate morphology." This finding suggests some models for regeneration of
      this neuroepithelium, including the possibility that mature supporting cells
      could transform directly into hair cells. The present Mini-Review discusses some
      of the models for neural regeneration that future studies might address in the
      light of our current knowledge and the new report. The possibility is raised that
      transitional forms of hair cell and supporting cell precursors may reside in the
      inner ear in a quiescent state until stimulated by damage.

PMID- 15468176
TI  - Preconditioning enhances the expression of mitochondrial antioxidant thioredoxin
      2 in the forebrain of rats exposed to severe hypobaric hypoxia.
AB  - The impact of severe hypoxia and preconditioning on the expression of the
      mitochondrial antioxidant thioredoxin-2 (Trx-2) in rat hippocampus (CA1, CA2, CA3
      fields, and dentate gyrus) and neocortex was studied by immunocytochemistry. The
      preconditioning consisted of three trials of mild hypobaric hypoxia (360 Torr, 2
      hr) spaced at 24 hr. The last trial was followed by severe hypobaric hypoxia (180
      Torr, 3 hr) 24 hr later. Both in hippocampus and in neocortex, severe hypobaric
      hypoxia resulted in enhanced Trx-2 expression at 3 hr, followed by a slight
      decline in Trx-2 levels, which nevertheless remained increased at 24 hr elsewhere
      except for the CA1 region. The preconditioning considerably augmented severe
      hypoxia-induced Trx-2 immunoreactivity, affecting both the number of
      immunoreactive cells and the intensity of immunostaining. The findings suggest a
      role for Trx-2 in the formation of brain hypoxic/ischemic tolerance accomplished
      by the preconditioning.

PMID- 15468177
TI  - Retinal glutamate transporter activity persists under simulated ischemic
      conditions.
AB  - Elevated extracellular concentrations of the neurotransmitter glutamate are
      neurotoxic and directly contribute to CNS damage as a result of ischemic
      pathologies. However, the main contributors to this uncontrolled rise in
      glutamate are still unconfirmed. It has been reported that the reversal of high
      affinity glutamate transporters is a significant contributing factor. Conversely,
      it has also been observed that these transporters continue to take up glutamate,
      albeit at a reduced saturation concentration, under ischemic conditions. We
      sought to determine whether glutamate transporters continue to remove glutamate
      from the extracellular space under ischemic conditions by pharmacologically
      modulating the activity of high-affinity retinal glutamate transporters during
      simulated ischemia in vitro. Retinal glutamate transporter activity was
      significantly reduced under these ischemic conditions. The suppression of retinal
      glutamate transporter activity, with the protein kinase C inhibitor
      chelerythrine, significantly reduced ischemic glutamate uptake and enhanced
      retinal neurodegeneration. These findings imply a limited but protective role for
      retinal glutamate transporters under certain ischemic conditions, suggesting that
      pharmacological enhancement of high-affinity glutamate transporter activity may
      reduce tissue damage and loss of function resulting from toxic extracellular
      glutamate concentrations.

PMID- 15468178
TI  - Habituation to a test apparatus during associative learning is sufficient to
      enhance muscarinic acetylcholine receptor-immunoreactivity in rat suprachiasmatic
      nucleus.
AB  - The suprachiasmatic nucleus (SCN) is engaged in modulation of memory retention
      after (fear) conditioning, but it is unknown which pathways and neurotransmitter
      system(s) play a role in this action. Here we examine immunocytochemically
      whether muscarinic acetylcholine receptors (mAChRs), mediating cholinergic signal
      transduction in the SCN, are involved. For this purpose, mAChR immunoreactivity
      (mAChR-ir) was studied in the SCN after various stages of passive shock avoidance
      (PSA) and active shock avoidance (ASA) training and, for ASA, at various
      posttraining time points. mAChR-ir was significantly enhanced in SCN neurons as a
      result of the training procedure, and the number of mAChR-positive glial cells in
      the SCN increased significantly. The increase in mAChR-ir as a result of PSA and
      ASA training was not due to fear conditioning or the number of correct avoidances
      (in case of ASA training) but rather to behavioral arousal as a consequence of
      (brief) exposure to a novel environment (the test apparatus). This finding was
      confirmed by a cage-change experiment in which the rats were allowed to stay in a
      novel cage for 15 min or 24 hr. Only the brief exposure to the fresh cage
      triggered alterations for SCN mAChRs 24 hr later. These results shed new light on
      a possible function of the cholinergic system in the SCN mediated by mAChRs in
      relation to modulation of memory processes and demonstrate that behavioral
      arousal during (the habituation stage of) a learning task is sufficient to alter
      the mAChR system in the SCN.

PMID- 15468179
TI  - Hippocampal neurotrophin levels after injury: Relationship to the age of the
      hippocampus at the time of injury.
AB  - Aging impairs the competence of the hippocampus for synaptic reorganization after
      injury. This potentially is due to the inability of the aging hippocampus to up
      regulate the critical neurotrophic factors for prolonged periods after injury to
      levels at which they can stimulate neurite outgrowth and facilitate synaptic
      reorganization. We hypothesize that the concentrations of neurotrophins in the
      hippocampus after injury depend on the age at the time of injury. We quantified
      the concentrations of brain-derived neurotrophic factor (BDNF), nerve growth
      factor (NGF), and neurotrophin-3 (NT-3) in the hippocampus of young, middle-aged,
      and aged Fischer 344 rats at 4 days after kainic acid (KA)-induced injury. In
      comparison with the age-matched intact hippocampus, the KA-lesioned hippocampus
      exhibited increased levels of BDNF and NGF in all three age groups. In contrast,
      the NT-3 concentration was unaltered after KA lesion. Notwithstanding similar
      percentage increases in BDNF after injury, the lesioned middle-aged and aged
      hippocampus contained 45-52% less BDNF than the lesioned young hippocampus. NGF
      and NT-3 levels after injury were comparable across the three age groups,
      however. Furthermore, lower BDNF concentration in the injured aging hippocampus
      was associated with normal astrocytic response but significantly diminished
      microglial reaction. Thus, in comparison with the injured young hippocampus, the
      injured aging hippocampus contains considerably less BDNF but similar levels of
      NGF and NT-3. Lower BDNF levels in the injured aging hippocampus might underlie
      the diminished spontaneous healing response observed in the aging hippocampus
      after injury, particularly in terms of synaptic reorganization and dentate
      neurogenesis.

PMID- 15468180
TI  - Quantifying intermolecular interactions: guidelines for the molecular recognition
      toolbox.
AB  - Molecular recognition events in solution are affected by many different factors
      that have hampered the development of an understanding of intermolecular
      interactions at a quantitative level. Our tendency is to partition these effects
      into discrete phenomenological fields that are classified, named, and divorced:
      aromatic interactions, cation-pi interactions, CH-O hydrogen bonds, short strong
      hydrogen bonds, and hydrophobic interactions to name a few.1 To progress in the
      field, we need to develop an integrated quantitative appreciation of the relative
      magnitudes of all of the different effects that might influence the molecular
      recognition behavior of a given system. In an effort to navigate undergraduates
      through the vast and sometimes contradictory literature on the subject, I have
      developed an approach that treats theoretical ideas and experimental observations
      about intermolecular interactions in the gas phase, the solid state, and solution
      from a single simplistic viewpoint. The key features are outlined here, and
      although many of the ideas will be familiar, the aim is to provide a
      semiquantitative thermodynamic ranking of these effects in solution at room
      temperature.

PMID- 15468181
TI  - Arylamine-substituted hexa-peri-hexabenzocoronenes: facile synthesis and their
      potential applications as "coaxial" hole-transport materials.

PMID- 15468182
TI  - A DNA nanomachine based on a duplex-triplex transition.

PMID- 15468183
TI  - A strategy for functional proteomic analysis of glycosidase activity from cell
      lysates.

PMID- 15468184
TI  - A beta-carboline-1-one mimic of the anticancer Amaryllidaceae constituent
      pancratistatin: synthesis and biological evaluation.

PMID- 15468186
TI  - Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum
      prostate-specific antigen level after radical prostatectomy and/or radiation
      therapy.
AB  - BACKGROUND: The objective of this study was to assess the biologic activity of
      rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist that
      has been approved to treat type 2 diabetes, in men with recurrent prostate
      carcinoma using change in prostate specific antigen (PSA) doubling time (PSADT)
      as the primary outcome variable. METHODS: Men with histologically confirmed
      prostate carcinoma, no recent hormone therapy, a rising serum PSA level after
      radical prostatectomy and/or radiation therapy, and no radiographic evidence of
      metastases were assigned randomly to receive either oral rosiglitazone (4 mg
      twice daily) or placebo. The treatment was continued until the men developed
      disease progression or adverse effects. A positive outcome was defined as a
      posttreatment PSADT > 150% the baseline PSADT and no new metastases. RESULTS: One
      hundred six men were enrolled. The median treatment duration was 315 days for men
      in the placebo group and 338 days for men in the rosiglitazone group (P = 0.28).
      Forty percent of men in the in the placebo group and 38% of men in the
      rosiglitazone group had a posttreatment PSADT > 150% of the baseline PSADT and no
      new metastases (P = 1.00). In exploratory analyses, the rate of a positive
      outcome remained higher than expected in the placebo group, even when a positive
      outcome was redefined using more stringent criteria. The time to disease
      progression was similar between the groups. CONCLUSIONS: Rosiglitazone did not
      increase PSADT or prolong the time to disease progression more than placebo in
      men with a rising PSA level after radical prostatectomy and/or radiation therapy.
      The unexpected discordance between baseline and posttreatment PSADT in the
      placebo group reinforced the importance of randomized controlled trials in this
      setting.

PMID- 15468187
TI  - Cranial nerve deficits in patients with metastatic prostate carcinoma: clinical
      features and treatment outcomes.
AB  - BACKGROUND: Cranial nerve lesions due to metastases from prostate carcinoma to
      the skull base are an uncommon yet clinically significant finding. METHODS: The
      authors report the clinical features, treatment, and outcomes for 15 patients who
      presented with cranial nerve palsies complicating metastatic prostate carcinoma.
      Patient charts identified from a Fox Chase Cancer Center treatment data base were
      reviewed. RESULTS: All patients had hormone-refractory disease at the time of
      symptom onset. Twelve of 15 patients had received prior chemotherapy, and 13 of
      15 patients had received prior radiation therapy to areas of bony pain. Symptoms
      varied from recognized clinical syndromes involving multiple cranial nerves to
      isolated cranial nerve lesions. All patients had lesions at the skull base that
      were visualized on computed tomography scans or magnetic resonance images. All
      patients were treated with palliative radiation therapy to either the whole brain
      or the skull base. Fourteen of 15 patients had a clinical (either partial or
      complete) response to radiation therapy. All responding patients subsequently
      died of prostate carcinoma without worsening of residual or development of new
      cranial nerve symptoms. Ten of 15 patients (67%) died within 3 months of
      developing symptoms, and the remaining 5 patients lived between 9 months and 31
      months from onset of symptoms. CONCLUSIONS: The authors concluded that palliative
      radiation therapy should be considered in this heterogeneous group of patients
      given the potential for significant symptom improvement.

PMID- 15468188
TI  - Glucocorticoid administration in antiemetic therapy: is it safe?
AB  - BACKGROUND: Although glucocorticoids are often used in cancer therapy, in
      particular to enhance the effectiveness of antiemetic therapy, they have been
      associated with impaired tumor apoptosis and an increased frequency of metastases
      in some reports. The current study aimed to determine whether glucocorticoid
      treatment had an adverse effect on outcomes in patients with ovarian carcinoma.
      METHODS: Records of patients with ovarian carcinoma who were scheduled to receive
      at least six courses of systemic chemotherapy were reviewed. Patients were
      grouped into those who had or had not received corticosteroid medication as a
      part of general antiemetic prophylaxis before chemotherapy, and details of
      hematologic parameters during treatment and disease recurrence-free and overall
      survival were recorded. RESULTS: Altogether, 245 patients with ovarian carcinoma
      had received chemotherapy. Of these, 62 had been given concurrent glucocorticoid
      treatment and 183 had not. The two patient groups were well balanced with respect
      to disease stage and other prognostic factors. Kaplan-Meier analyses showed no
      significant differences in survival between the groups. Patients who received
      glucocorticoid treatment had significantly higher leukocyte values in the days
      immediately after chemotherapy, higher nadir leukocyte values, and higher counts
      before subsequent courses of chemotherapy (P < 0.01; Levene test, t test)
      compared with patients who did not receive glucocorticoid treatment. As a result,
      the initial treatment targets were achieved significantly more often in the
      glucocorticoid group (P = 0.007; chi-square test). CONCLUSIONS: There was no
      evidence that glucocorticoid treatment had a negative effect on outcomes in these
      patients. Glucocorticoids may exert protective effects on the bone marrow.

PMID- 15468190
TI  - Proteomic approach to identify acute phase response-related proteins with low
      molecular weight in loach skin following injury.
AB  - Proteome analysis by two-dimensional gel electrophoresis (2-DE) together with
      mass spectrometry was applied to screen acute phase response (APR)-related
      proteins with low molecular weight in loach skin following injury. Furthermore,
      Western blotting and function tests were applied to confirm the results obtained
      from the proteomic study. Fifteen APR-related proteins with sixteen spots (PLA
      with two spots) on a 2-DE map were identified in this study. Furthermore, six
      were known acute phase proteins including galactose-binding lectin (GBL),
      lysozyme, C3, CD59, double PLA and 50s ribosomal protein; while ATP kinase, zinc
      finger protein 183, alpha-neurotoxin homology, angiostatin, serine/threonine
      kinase, metalloproteinase inhibitor, regulator of G-protein 4, cryptdin-9 and
      disintegrin trigranin were found by our lab to be APR-related proteins. In
      addition, our results suggest that proteomes with low molecular weight can be
      characterized by 2-DE with a Tris-tricine system followed by mass spectrometry.

PMID- 15468191
TI  - Endostatin gene therapy delivered by Salmonella choleraesuis in murine tumor
      models.
AB  - BACKGROUND: Some anaerobic and facultatively anaerobic bacteria have been used
      experimentally as anticancer agents because of their selective growth in tumors.
      In this study, we exploited attenuated Salmonella choleraesuis as a tumoricidal
      agent and a vector to deliver the endostatin gene for tumor-targeted gene
      therapy. METHODS: Attenuated S. choleraesuis carrying a eukaryotic expression
      plasmid encoding reporter gene was used to evaluate its abilities of tumor
      targeting and gene delivery in three syngeneic murine tumor models. Furthermore,
      S. choleraesuis carrying the endostatin expression vector was administered
      intraperitoneally into tumor-bearing mice, and its antitumor effect was
      evaluated. RESULTS: Systemically administered S. choleraesuis preferentially
      accumulated within tumors for at least 10 days, forming tumor-to-normal tissue
      ratios exceeding 1000-10,000 : 1. Transgene expression via S. choleraesuis
      mediated gene transfer also persisted for at least 10 days. Host immune responses
      and tumor hypoxia may influence tumor-targeting potential of S. choleraesuis.
      When systemically administered into mice bearing melanomas or bladder tumors, S.
      choleraesuis carrying the endostatin expression vector significantly inhibited
      tumor growth by 40-70% and prolonged survival of the mice. Furthermore,
      immunohistochemical studies in the tumors revealed decreased intratumoral
      microvessel density, reduced expression of vascular endothelial growth factor
      (VEGF), and increased infiltration of CD8(+) T cells. CONCLUSIONS: These results
      suggest that tumor-targeted gene therapy using S. choleraesuis carrying the
      endostatin expression vector, which exerts tumoricidal and antiangiogenic
      activities, represents a promising strategy for the treatment of solid tumors.

PMID- 15468192
TI  - Inducible production of erythropoietin using intramuscular injection of block
      copolymer/DNA formulation.
AB  - BACKGROUND: We have previously shown that intramuscular injection of plasmid DNA
      formulated with a non-ionic amphiphile synthetic vector [poly(ethylene oxide)(13)
      poly(propylene oxide)(30)-poly(ethylene oxide)(13) block copolymer; PE6400]
      increases reporter gene expression compared with naked DNA. We have now
      investigated this simple non-viral formulation for production of secreted
      proteins from the mouse skeletal muscle. METHODS: Plasmids encoding either
      constitutive human secreted alkaline phosphatase or murine erythropoietin
      inducible via a Tet-on system were formulated with PE6400 and intramuscularly
      injected into the mouse tibial anterior muscle. RESULTS: PE6400/DNA formulation
      led to an increased amount of recombinant alkaline phosphatase secreted from
      skeletal muscle as compared with naked DNA. In the presence of doxycycline, a
      single injection of 10 microg plasmid encoding inducible murine erythropoietin
      formulated with PE6400 significantly increased the hematocrit, whereas the same
      amount of DNA in the absence of PE6400 had no effect. The increase in the
      hematocrit was stable for 42 days. The tetracycline-inducible promoter permitted
      pharmacological control of hematocrit level after DNA intramuscular injection.
      However, 4 months post-injection the hematocrit returned to its pre-injection
      value, even in the presence of doxycycline. This phenomenon was likely caused by
      an immune response against the tetracycline-activated transcription factor.
      CONCLUSIONS: Intramuscular injection of plasmid DNA formulated with PE6400
      provides an efficient and simple method for secretion and production of non
      muscle proteins.

PMID- 15468193
TI  - Exploiting dendritic cells for cancer immunotherapy: genetic modification of
      dendritic cells.
AB  - Dendritic cells (DCs) are pivotal regulators of immune reactivity and immune
      tolerance. The observation that DCs can recruit naive T cells has invigorated
      cancer immunology and led to the proposal of DCs as the basis for vaccines
      designed for the treatment of cancer. Designing effective strategies to load DCs
      with antigens is a challenging field of research. The successful realization of
      gene transfer to DCs will be highly dependent on the employed vector system.
      Here, we review various viral and non-viral gene transfer systems, and discuss
      their distinct characteristics and possible advantages and disadvantages in
      respect to their use in DC-based immunotherapy.

PMID- 15468194
TI  - Growth factor displayed on the surface of retroviral particles without
      manipulation of envelope proteins is biologically active and can enhance
      transduction.
AB  - BACKGROUND: The therapeutic potential of retroviruses can be significantly
      enhanced by display of specific molecules on the retroviral surface. This has
      been conventionally achieved by the manipulation of retroviral envelope proteins.
      In this report we have tested whether the natural budding mechanism of the
      retrovirus could be exploited to incorporate a specific molecule into the
      retroviral surface. METHODS: Retroviral packaging cells were engineered to
      express the membrane-bound form of human stem cell factor (mbSCF). Surface
      expression of mbSCF on retroviral packaging cells was confirmed by
      immunofluorescence and flow cytometry. Incorporation of mbSCF into retroviral
      particles was demonstrated by virus-binding assay and immunomagnetic capture of
      virus using antibody to SCF. Retroviral supernatants were tested for activity of
      the incorporated cytokine by proliferation assays on factor-dependent cells.
      Amphotropic retrovirus displaying surface mbSCF was used to transduce SCF
      receptor-positive haematopoietic cells. RESULTS: Retroviruses incorporating
      surface SCF showed increased levels of binding to cells (MO7e) expressing the SCF
      receptor, c-kit. mbSCF displayed on the viral surface retained levels of
      biological activity comparable with those of soluble recombinant growth factor.
      Transduction of c-kit-positive target cells with viruses displaying mbSCF showed
      enhanced levels of transduction in comparison with unmodified viruses.
      CONCLUSIONS: Expression of the membrane-bound form of human stem cell factor
      (mbSCF) on the surface of retroviral packaging cells allows its efficient
      incorporation into retrovirus particles in a biologically active form, opening up
      the possibility for the use of retroviral display in many therapeutic areas, such
      as in gene therapy, drug delivery and in the development of novel vaccines.

PMID- 15468195
TI  - Changes in detrusor smooth muscle myosin heavy chain mRNA expression following
      spinal cord injury in the mouse.
AB  - AIMS: Smooth muscle myosin heavy chain (SMMHC) isoform composition has been shown
      to be developmentally regulated and to be associated with functional changes in
      smooth muscle activity. In this study, we sought to determine expression patterns
      of SMMHC isoforms in a murine model of spinal cord injury (SCI) and to compare
      these expression patterns to neurologic, cytometric, and morphometric findings.
      MATERIALS AND METHODS: Baseline cystometry was performed on adult, female mice
      followed by either thoracic spinal cord transection (SCI) or sham operation
      (Sham). At 1, 3, or 6 weeks postoperatively neurologic evaluation and cystometry
      were performed, bladders were harvested, and expression patterns of SMMHC
      isoforms (SM1 vs. SM2 and SMA vs. SMB) were assessed by RT-PCR. Morphometrics
      utilizing computer-assisted color image analysis was also performed on all
      bladders. RESULTS: There was a significant increase in bladder weight and
      capacity 1 week following SCI which normalized over time, however, morphometric
      analysis did not reveal an alteration in tissue composition amongst the three
      groups. One week following SCI, SM1 was predominantly expressed over SM2 and
      began to normalize at 3 weeks. This coincided with the emergence of reflex
      voiding and detrusor overactivity. SMA was expressed following SCI only, and the
      number of bladders found to express SMA decreased with increasing duration since
      SCI. CONCLUSIONS: Smooth muscle myosin heavy chain mRNA expression patterns
      appear to be affected by SCI. We believe the induction of SMA may be a factor in
      altered bladder function following injury.

PMID- 15468196
TI  - Preparation and characterization of novel physically cross-linked hydrogels
      composed of poly(vinyl alcohol) and amine-terminated polyamidoamine dendrimer.
AB  - Poly(vinyl alcohol) (PVA) and polyamidoamine (PAMAM) dendrimers are water
      soluble, biocompatible and biodegradable polymers, which have been widely applied
      in biomedical fields. In this paper, novel physically cross-linked hydrogels
      composed of PVA and amine-terminated PAMAM dendrimer G6-NH(2) were prepared by
      cyclic freezing/thawing treatment of aqueous solutions containing PVA and G6
      NH(2). The FT-IR analysis and elemental analysis indicated that PAMAM dendrimer
      G6-NH(2) was successfully introduced into the formed hydrogels, possibly via
      hydrogen bonds among hydroxyl groups, amide groups and amino groups in PVA and
      PAMAM dendrimer in the process of freezing-thawing cycle. Compared with
      physically cross-linked PVA hydrogel, PVA/G6-NH(2) hydrogels show higher swelling
      ratios and faster re-swelling rate due to the higher hydrophilicity of PAMAM
      dendrimer G6-NH(2). Higher contents of G6-NH(2) in PVA/G6-NH(2) hydrogels
      resulted in higher swelling ratios and faster re-swelling rates. With increasing
      freezing/thawing cyclic times, the swelling ratios and re-swelling rates of
      PVA/G6-NH(2) hydrogels decreased, which is similar to that of physically cross
      linked PVA hydrogel. Combining the special host property of polyamidoamine
      dendrimer, these novel physically cross-linked hydrogels are expected to have
      potential use in drug delivery, including improving drug-loading amounts in
      hydrogels and prolonging drug release time. Swelling ratios of physically cross
      linked PVA/G6-NH(2)-50 hydrogels prepared by three, six, nine freezing/thawing
      cycles. The swelling equilibrium experiments were carried out in distilled water
      at 25 degrees C.

PMID- 15468197
TI  - Characterization of riboflavin-photosensitized changes in aqueous solutions of
      alginate by dynamic light scattering.
AB  - The effect of irradiation, in the wavelength range of 310-800 nm, on aqueous
      solutions (pH = 7.4) of alginate in the presence of the photosensitizer
      riboflavin (RF) has been investigated with the aid of dynamic light scattering
      (DLS). Under aerobic conditions light irradiation of RF causes scission of the
      polymer chains which affects the polymer dynamics. The time correlation data
      obtained from DLS experiments showed at all conditions the existence of two
      relaxation modes: one single exponential at short times, followed by a stretched
      exponential at longer times. The slow relaxation time revealed, over the whole
      considered concentration range, lower values for the alginate/RF system, whereas
      no effect of photochemical degradation was observed for the fast relaxation time
      in the semidilute regime. The results suggest that the photochemically induced
      fragmentation of alginate affects the slow relaxation mode, associated with
      disengagement relaxation of individual chains or cluster relaxation, in a similar
      way as the zero-shear viscosity. These findings provide detailed insight into the
      dynamics of the polymer matrix, and this knowledge can be useful in the context
      of controlled-release delivery of drugs. The chemical units of alginate (M =
      mannuronic acid and G = guluronic acid).

PMID- 15468198
TI  - Dye affinity hollow fibers for albumin purification.
AB  - Reactive Green HE 4BD was immobilized on polyamide (PA) hollow fibers for human
      serum albumin (HSA) adsorption from both aqueous solutions and human plasma.
      Different amounts of Reactive Green HE 4BD were incorporated on the PA hollow
      fibers by changing the dye attachment conditions, i.e. the initial dye
      concentration and the addition of sodium carbonate and sodium chloride. The
      maximum amount of dye attachment was obtained as 39.4 micromol x g(-1) when the
      hollow fibers were treated with 3 M HCl for 30 min before performing the dye
      attachment. HSA adsorption onto unmodified and dye-attached hollow fibers was
      investigated batchwise. The non-specific adsorption of HSA was low (6.0 mg/g
      hollow fiber). Dye attachment onto the hollow fibers significantly increased the
      HSA adsorption (86.7 mg/g). The maximum HSA adsorption was observed at pH 5.0.
      Higher HSA adsorption was observed from human plasma (198 mg HSA/g). The
      desorptions were performed by adding 0.1 M Tris/HCl buffer containing 0.5 M NaSCN
      or 1.0 M NaCl to the HSA solutions in which adsorption equilibria had been
      reached. The desorption results demonstrated that the adsorption of HSA to the
      adsorbent was reversible. Chemical structure of Reactive Green HE-4BD.

PMID- 15468199
TI  - Supramolecular hydrogel formation based on inclusion complexation between
      poly(ethylene glycol)-modified chitosan and alpha-cyclodextrin.
AB  - Supramolecular hydrogels have been prepared on the basis of polymer inclusion
      complex (PIC) formation between poly(ethylene glycol) (PEG)-modified chitosans
      and alpha-cyclodextrin (alpha-CD). A series of PEG-modified chitosans were
      synthesized by coupling reactions between chitosan and monocarboxylated PEG using
      water-soluble carbodiimide (EDC) as coupling agent. With simple mixing, the
      resultant supramolecular assembly of the polymers and alpha-CD molecules led to
      hydrogel formation in aqueous media. The supramolecular structure of the PIC
      hydrogels was confirmed by differential scanning calorimetry (DSC), X-ray
      diffraction, and (13)C cross-polarized/magic-angle spinning (CP/MAS) NMR
      characterization. The PEG side-chains on the chitosan backbones were found to
      form inclusion complexes (ICs) with alpha-CD molecules, resulting in the
      formation of channel-type crystalline micro-domains. The IC domains play an
      important role in holding together hydrated chitosan chains as physical
      junctions. The gelation property was affected by several factors including the
      PEG content in the polymers, the solution concentration, the mixing ratio of host
      and guest molecules, temperature, pH, etc. All the hydrogels in acidic conditions
      exhibited thermo-reversible gel-sol transitions under appropriate conditions of
      mixing ratio and PEG content in the mixing process. The transitions were induced
      by supramolecular association and dissociation. These supramolecular hydrogels
      were found to have phase-separated structures that consist of hydrophobic
      crystalline PIC domains, which were formed by the host-guest interaction between
      alpha-CD and PEG, and hydrated chitosan matrices below the pK(a).The formation of
      inclusion complexes between alpha-cyclodextrin and PEG-modified chitosan leads to
      the formation of hydrogels that can undergo thermo-reversible supramolecular
      dissociation.

PMID- 15468200
TI  - Biomimetic polymer/apatite composite scaffolds for mineralized tissue
      engineering.
AB  - The material surface must be considered in the design of scaffolds for bone
      tissue engineering so that it supports bone cells adhesion, proliferation and
      differentiation. A biomimetic approach has been developed as a 3D surface
      modification technique to grow partially carbonated hydroxyapatite (the bonelike
      mineral) in prefabricated, porous, polymer scaffolds using a simulated body fluid
      in our lab. For the rational design of scaffolding materials and optimization of
      the biomimetic process, this work focused on various materials and processing
      parameters in relation to apatite formation on 3D polymer scaffolds. The apatite
      nucleation and growth in the internal pores of poly(L-lactide) and poly(D,L
      lactide) scaffolds were significantly faster than in those of poly(lactide-co
      glycolide) scaffolds in simulated body fluids. The apatite distribution was
      significantly more uniform in the poly(L-lactide) scaffolds than in the
      poly(lactide-co-glycolide) scaffolds. After incubation in a simulated body fluid
      for 30 d, the mass of poly(L-lactide) scaffolds increased approximately 40%,
      whereas the mass of the poly(lactide-co-glycolide) scaffolds increased by about
      15% (see Figure). A higher ionic concentration and higher pH value of the
      simulated body fluid enhanced apatite formation. The effects of surface
      functional groups on apatite nucleation and growth were found to be more complex
      in 3D scaffolds than on 2D films. Surprisingly enough, it was found that carboxyl
      groups significantly reduced the apatite formation, especially on the internal
      pore surfaces of 3D scaffolds. These findings are critically important in the
      rational selection of materials and surface design of 3D scaffolds for
      mineralized tissue engineering and may contribute to the understanding of
      biomineralization as well.SEM micrograph of a poly(L-lactide) scaffold.

PMID- 15468201
TI  - Direct visualization of straw cell walls by AFM.
AB  - The structural relationship of cellulose, hemicellulose, and lignin in plant cell
      walls is still a mystery needing to be explored. By using atomic force microscopy
      (AFM) the surface of straw at different layers was directly observed, and the
      structural characteristics were analyzed by topographic analysis and FT-IR
      spectra. It was found that a compact layer of wax covered the outside of the
      straw, which protects the straw from insects and microorganisms. At the boundary
      of the primary and second wall there appears a network structure of cellulose and
      hemicellulose, with some lignin localised on the surface of the network. It is
      consistent with the model of a cell wall suggested by Vincent. Inside the second
      cell wall, there is a layer mainly composed of a cellulose crystalline region.
      High-resolution AFM observation reveals that the crystalline structure consists
      of both triclinic and monoclinic unit cells. An AFM phase image showing the
      structural relation between cellulose microfibrils, hemicellulose, and lignin in
      the straw cell wall.

PMID- 15468202
TI  - Polymeric controlled release formulations of niclosamide for control of
      Biomphalaria alexandrina, the vector snail of schistosomiasis.
AB  - Schistosomiasis is one of the most important public health problems in many
      developing countries. The present study was conducted to investigate the effect
      of the polymeric niclosamide formulations against Biomphalaria alexandrina
      snails, the intermediate host of Schistosoma mansoni in Egypt. Three new
      polymeric formulations were prepared for the molluscicide niclosamide. The
      formulations were prepared either by the chemical modifications of poly(glycidyl
      methacrylate) or by physical entrapment of the niclosamide in calcium alginate
      beads. The release of the niclosamide from the polymeric formulations was
      investigated. The activity of the prepared formulations against Biomphalaria
      alexandrina was investigated. The results obtained revealed higher potency for
      polymerized niclosamide B3 than B1; the lowest potency was revealed for B2. After
      an exposure period of 24 hours, LC(50) values were 0.073, 0.098 and 1.09 ppm for
      B3, B1 and B2, respectively. In addition, the molluscicidal potency of the test
      polymeric niclosamide was age-dependent, where old snails were more tolerant to
      the test solutions than young and newly hatched snails. The results also
      indicated that the molluscicidal activity of B3 was extended for 21 days and 17
      days for B1, compared with 5 days for free niclosamide. However, the
      molluscicidal potency of the polymerized niclosamide was increased after boiling
      for one hour, and was increased with increasing the pH of the medium to pH 9. In
      addition, their potency was increased with decreasing the water hardness
      concentrations (CaCO(3)).Molluscicidal activity of free niclosamide and its
      polymeric formulations vs. exposure time.

PMID- 15468203
TI  - ICBP 2003. Proceedings of the 1st IUPAC International Conference on Bio-Based
      Polymers. Saitama, Japan, 12-14 November 2003.

PMID- 15468204
TI  - Evolution of polyhydroxyalkanoate (PHA) production system by "enzyme evolution":
      successful case studies of directed evolution.
AB  - Biotechnological studies towards the biosynthesis of polyhydroxyalkanoates (PHAs)
      biopolyesters have extensively progressed through the development of various
      metabolic engineering strategies. Historically, efficient PHA production has been
      achieved using the fermentation technology of naturally occurring PHA-producing
      bacteria based on external substrate manipulation (1st generation), and
      subsequent reinforcement with recombinant gene technology (2nd generation). More
      recently, "enzyme evolution" is becoming the 3rd generation approach for PHA
      production. A break-through in the chemical synthesis of macromolecules with
      desirable properties was achieved by the development of prominent chemical
      catalysts via "catalyst evolution", as represented by a series of Ziegler-Natta
      catalysts. Thus, one can easily accept the concept that the molecular evolution
      of the biocatalysts (enzymes) relevant to PHA synthesis will provide us with a
      chance to create novel PHA materials with high performance. The first trial of an
      in vitro enzyme evolution in PHA biosynthesis was reported by our group in 2001.
      The following literature data, as well as our own experimental results devoted to
      this new approach, have been accumulated over a short time. This review article
      focuses specifically on the concept and current case studies of the application
      of "enzyme evolution" to PHA biosynthesis.

PMID- 15468205
TI  - Fermentative production of chemicals that can be used for polymer synthesis.
AB  - The fermentative production of chemicals that can be used as monomers for the
      synthesis of polymers has become an important topic in biotechnology research
      because of the limited nature of petroleum and environmental issues. In
      particular, the fermentative production of metabolites such as dicarboxylic
      acids, amino acids, and diols, which are suitable as building blocks for
      subsequent polymerization, has attracted much attention. Various wild-type and
      metabolically engineered microorganisms have been developed for the efficient
      production of these chemicals from renewable resources. In addition, the
      development of fermentation strategies to achieve the highest possible
      productivities has been another focus of research, considering that these
      monomers should be produced at costs low enough to compete with petroleum-derived
      ones. In this paper, the metabolic pathways leading to the synthesis of such
      important monomers including succinic acid, lactic acid, fumaric acid, propan-1,2
      diol, and propan-1,3-diol are reviewed. In addition, the metabolic engineering
      and fermentation strategies for their production are reviewed.

PMID- 15468206
TI  - Microbial polythioesters.
AB  - This feature article describes the current knowledge on biosynthesis of
      polythioesters (PTEs), which are exclusively accumulated by microorganisms
      capable to synthesize the well-known polyhydroxyalkanoates (PHAs). Two bacterial
      PTE biosynthesis systems are discussed, both are depending on the cultivation
      conditions and appropriate feeding regimes. The first system comprises the
      production of PTE copolymers by Ralstonia eutropha, and the second system has
      been established in recombinant Escherichia coli to produce PTE homopolymers.
      Furthermore, synthetic PTEs and other related sulfur containing biopolymers are
      briefly summarized.

PMID- 15468207
TI  - Structure and structural changes of the silk fibroin from Samia cynthia ricini
      using nuclear magnetic resonance spectroscopy.
AB  - The structure of silk fibroin from a wild silkworm, S. c. ricini, the amino acid
      sequence of which consists of repeated poly-Ala and Gly-rich regions, was
      examined by using solution and solid-state NMR methods. The structural transition
      of the silk fibroin in aqueous solution was monitored by using 13C solution NMR
      spectroscopy as a function of temperature. The fast exchange with respect to the
      chemical shift between the helix and coil conformations was observed in the poly
      Ala region and the slow conformational change from alpha-helix to random coil was
      observed for the Gly residue adjacent to the N-terminal Ala residue of the poly
      Ala region. The torsion angles of several Ala and Gly residues in the model
      peptide, GGAGGGYGGDGG(A)12GGA-GDGYGAG, were determined by the conformation
      dependent 13C chemical shifts, rotational echo double resonance (REDOR) and 2D
      spin-diffusion NMR methods. The solid-state NMR analysis leads to the precise
      silk structure before spinning, where the poly-Ala sequence takes a typical alpha
      helix pattern with a tightly winded helical structure at both terminal regions of
      the poly-Ala sequence. This is expected to stabilize the alpha-helical structure
      of the poly-Ala region in S. c. ricini silk fibroin from the silkworm.

PMID- 15468208
TI  - Comonomer-unit compositions, physical properties and biodegradability of
      bacterial copolyhydroxyalkanoates.
AB  - The comonomer-unit compositions and their distribution of as-produced bacterial
      copolyesters, including poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3
      hydroxy-butyrate-co-3-hydroxypropionate), poly(3-hydroxybutyrate-co-3
      hydroxyhexanoate) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate) are described
      in this paper. Each copolyester sample can be comonomer-unit compositionally
      fractionated into several fractions, indicating that the original copolymers are
      mixtures of copolymers with different comonomer-unit compositions. The effects of
      comonomer-unit compositional distribution on thermal properties, crystallization,
      biodegradability and solid-state phase behavior are investigated using comonomer
      compositionally fractionated copolymers.

PMID- 15468209
TI  - Biodegradable aliphatic polyester ionomers.
AB  - A series of polyester-based ionomers containing dimethyl 5-sulfoisophthalate
      sodium salt (DMSI) with up to 5 mol-% diacid units was synthesized by two-step
      polycondensation. Furthermore a polylactic acid (PLA) was modified by introducing
      poly(ethylene-co-methacrylic acid) ionomers with different ion groups, such as
      Na, Li, and Zn, using the melt blending method. This review examines the effect
      of the ionic group on the dynamic mechanical properties, melt rheology,
      crystallization behavior, degradation behavior, and biocompatibility with human
      dermal cells, as well as the nucleating effect of poly(ethylene-co-methacrylic
      acid) ionomer in PLA.

PMID- 15468210
TI  - Degradable polyesters through chain linking for packaging and biomedical
      applications.
AB  - The major route to convert lactic acid to high-molecular-weight polymers is ring
      opening polymerization of lactide. We have investigated alternative synthesis
      routes based on oligomerization and chain linking to produce high-molecular
      weight thermoplastic degradable polymers cost-effectively. Chain linking also
      offers new possibilities to prepare degradable polyesters for biomedical
      applications by extending the range of polymer properties achievable. In this
      paper, we briefly review different chain linking techniques used in our
      laboratory. Typically, lactic acid prepolymers with molecular weights of around
      3,000-15,000 g x mol(-1) have been prepared by direct polycondensation. Hydroxyl
      terminated oligomers have been chain linked by using diisocyanate coupling
      agents, preferably 1,4-butane diisocyanate, forming poly(ester-urethanes).
      Poly(ester-amides) have been prepared by using 2,2'-bis(2-oxazoline) as coupling
      agent for carboxylic acid telechelic oligomers. Chain linking by end
      functionalization has been used in the preparation of poly(ester-anhydrides). In
      addition, a variety of crosslinked degradable polymers and copolymers have been
      synthesized through different crosslinking routes, by using methacrylic, itaconic
      or maleic double bonds or triethoxysilane moieties. A biodegradation test and
      ecotoxicological evaluation of the degradation products were carried out in
      addition to hydrolysis tests. Lactic acid based chain linked polymers were
      biodegradable and the degradation products were harmless. In hydrolysis tests,
      enzymatic degradation was pronounced in the chain linked poly(epsilon
      caprolactone).

PMID- 15468211
TI  - Environmentally degradable bio-based polymeric blends and composites.
AB  - Blends and composites based on environmentally degradable-ecocompatible synthetic
      and natural polymeric materials and fillers of natural origin have been prepared
      and processed under different conditions. Poly(vinyl alcohol) (PVA) was used as
      the synthetic polymer of choice by virtue of its capability to be processed from
      water solution or suspension as well as from the melt by blow extrusion and
      injection molding. Starch and gelatin were taken as the polymeric materials from
      renewable resources. The fillers were all of natural origin, as waste from food
      and agro-industry consisted of sugar cane bagasse (SCB), wheat flour (WF), orange
      peels (OR), apple peels (AP), corn fibres (CF), saw dust (SD) and wheat straw
      (WS). All the natural or hybrid formulations were intended to be utilized for the
      production of: a) Environmentally degradable mulching films (hydro-biomulching)
      displaying, in some cases, self-fertilizing characteristics by in situ spraying
      of water solutions or suspensions; b) Laminates and containers to be used in
      agriculture and food packaging by compression and injection molding followed by
      baking. Some typical prototype items have been prepared and characterized in
      relation to their morphological and mechanical properties and tested with
      different methodology for their propensity to environmental degradation and
      biodegradation as ultimate stage of their service life. A relationship between
      chemical composition and mechanical properties and propensity to biodegradation
      has been discussed in a few representative cases.

PMID- 15468212
TI  - Lactic acid-based functionalized polymers via copolymerization and chemical
      modification.
AB  - Poly(lactic acid) polymers (PLA) are presently the most attractive compounds in
      the field of artificial degradable and biodegradable polymers. In order to
      enlarge the family, and thus the range of accessible properties, stereocopolymers
      and copolymers with various co-monomers have been synthesized. However, very few
      are functionalized, i.e. include functional groups attached to the main chains or
      as part of the side chains. In the search for degradable PLA-type polymers
      bearing functional groups to serve as intermediates for further chemical
      modifications, we are exploring two different routes. The first one is
      copolymerization with a protected hydroxyl-bearing lactide-type monomer, namely 3
      (1,2,3,4-tetraoxobutyldiisopropylidene)dioxane-2,5-dione. The second route
      consists of the formation of a carbanionic site in the alpha-position to
      intrachain carbonyl functions by using lithium N,N-diisopropylamide followed by
      the coupling of electrophiles. Recent advances in this search are presented using
      several examples. In particular, it is shown that OH-functionalized PLA-type
      macromolecules can be made fluorescent by chemical coupling. It is also shown
      that substituents can be attached to PLA-type macromolecules in solution or to
      the surface of PLA-based devices selectively.

PMID- 15468213
TI  - Biosynthesis and compositional regulation of poly[(3-hydroxybutyrate)-co-(3
      hydroxyhexanoate)] in recombinant ralstonia eutropha expressing mutated
      polyhydroxyalkanoate synthase genes.
AB  - A new strategy for bacterial polyhydroxyalkanoate (PHA) production by recombinant
      Ralstonia eutropha PHB(-)4 harboring mutated PHA synthase genes (phaC(Ac)) from
      Aeromona caviae was investigated. The strain harboring wild-type phaC(Ac) gene
      produced a PHA copolymer consisting of (R)-3-hydroxybutyrate and (R)-3
      hydroxyhexanoate [P(3HB-co-3HHx)] with 3.5 mol-% of 3HHx fraction from soybean
      oil. When the mutants of phaC(Ac) gene were applied to this production system,
      3HHx fraction in copolymers was varied in the range of 0-5.1 mol-%. Thus, the
      regulation of PHA copolymer compositions has been achieved by the use of mutated
      PHA synthase genes.

PMID- 15468214
TI  - Mass spectrometry feedback control for synthesis of polyhydroxyalkanoate granule
      microstructures in Ralstonia eutropha.
AB  - Polyhydroxyalkanoate (PHA) granules with core-shell layered microstructure were
      synthesized in Ralstonia eutropha using periodic feeding of valeric acid into a
      growth medium containing excess fructose. The O2 consumption and CO2 evolution
      rates, determined by off-gas mass spectrometry, have been used as sensitive
      measures to indicate the type of nutrients utilized by R. eutropha during PHA
      synthesis. Domains of poly-3-hydroxybutyrate (PHB) were formed during polymer
      storage conditions when only fructose was present. Feeding of valeric acid
      (pentanoic acid) resulted in the synthesis of hydroxyvalerate (HV) monomers,
      forming a poly-3-hydroxybutyrate-co-valerate (PHBV) copolymer. The synthesis of
      desired polymer microstructures was monitored and controlled using online mass
      spectrometry (MS). The respiratory quotient (RQ) was unique to the type of
      polymer being synthesized due to increased O2 consumption during PHBV synthesis.
      MS data was used as the control signal for nutrient feeding strategies in the
      bioreactor. The core-shell structures synthesized were verified in cells using
      transmission electron microscopy after thin sectioning and staining with RuO4. It
      was demonstrated that the synthesis of core-shell microstructures can be
      precisely controlled utilizing a MS feedback control system.

PMID- 15468215
TI  - Metabolic engineering for the production of copolyesters consisting of 3
      hydroxybutyrate and 3-hydroxyhexanoate by Aeromonas hydrophila.
AB  - Aeromonas hydrophila 4AK4 was able to synthesize copolyesters consisting of 3
      hydroxybutyrate (3HB) and about 15 mol-% 3-hydroxyhexanoate (3HHx) (PHBHHx) when
      grown in long chain fatty acids such as dodecanoate regardless of growth
      conditions. To regulate the unit fraction in PHBHHx, phbA and phbB genes encoding
      beta-ketothiolase and acetoacetyl-CoA reductase in Ralstonia eutropha, were
      introduced into A. hydrophila 4AK4. When gluconate was used as cosubstrate of
      dodecanoate, the recombinant produced PHBHHx containing 3-12 mol-% 3HHx,
      depending on the gluconate concentration in media. Vitreoscilla hemoglobin gene,
      vgb, was also introduced into the above recombinant, resulting in improved PHBHHx
      content from 38 to 48 wt.-% in shake flask study. Fermentor studies also showed
      that increased gluconate concentration in medium containing dodecanoate promoted
      the recombinant strain harboring phbA and phbB genes to incorporate more 3HB unit
      into PHBHHx, resulting in reduced 3HHx fraction. Recombinant A. hydrophila
      harboring phbA, phbB and vgb genes demonstrated better PHBHHx productivity and
      higher conversion efficiency from dodecanoate to PHBHHx than those of the
      recombinant without vgb in fermentation study. Combined with the robust growth
      property and simple growth requirement, A. hydrophila 4AK4 appeared to be a
      useful organism for metabolic engineering.

PMID- 15468216
TI  - Synthesis and properties of graft copolymers based on poly(3-hydroxybutyrate)
      macromonomers.
AB  - Graft copolymers of poly(methyl methacrylate) with poly(3-hydroxybutyrate), PHB,
      segments as long side chains were prepared by the macromonomer method. PHB
      macromonomers were prepared from the esterification of oligomers with 2
      hydroxyethyl methacrylate at their carboxylic acid end. Esterification products
      displayed low polydispersity indices (ca. 1.2) and a functionality of over 83%,
      with a Mn of 2,020. Using free radical polymerization methods, the macromonomers
      were copolymerized with methyl methacrylate to yield graft (comb type) copolymers
      at different comonomer feed ratios. The graft copolymers contained from 0.5 to 14
      mol-% of PHB blocks, with a glass transition temperature decreasing from 100 to 3
      degrees C.

PMID- 15468217
TI  - Polymer alloys of Nodax copolymers and poly(lactic acid).
AB  - Properties of polymer alloys comprising poly(lactic acid) and Nodax copolymers
      are investigated. Nodax is a family of bacterially produced polyhydroxyalkanoate
      (PHA) copolymers comprising 3-hydroxybutyrate (3HB) and other 3-hydroxyalkanoate
      (3HA) units with side groups greater than or equal to three carbon units. The
      incorporation of 3HA units with medium-chain-length (mcl) side groups effectively
      lowers the crystallinity and the melt temperature, Tm, of this class of PHA
      copolymers, in a manner similar to that of alpha olefins controlling the
      properties of linear low density polyethylene. The lower Tm makes the material
      easier to process, as the thermal decomposition temperature of PHAs is then
      relatively low. The reduced crystallinity provides the ductility and toughness
      required for many plastics applications. When a small amount of ductile PHA is
      blended with poly(lactic acid) (PLA), a new type of polymer alloy with much
      improved properties is created. The toughness of PLA is substantially increased
      without a reduction in the optical clarity of the blend. The synergy between the
      two materials, both produced from renewable resources, is attributed to the
      retardation of crystallization of PHA copolymers finely dispersed in a PLA matrix
      as discrete domains.

PMID- 15468218
TI  - In-situ atomic force microscopy observation of enzymatic degradation in
      poly(hydroxyalkanoic acid) thin films: normal and constrained conditions.
AB  - The enzymatic degradation of lamellar crystals in poly(hydroxyalkanoic acid) thin
      films has been visualized by using in-situ dynamic force mode (tapping mode)
      atomic force microscopy (AFM) in buffer solution. It was found that
      poly(hydroxybutyric acid) (PHB) depolymerase from Ralstonia pickettii T1 degraded
      the thin surface layers formed at room temperature first, and that lamellar
      crystals formed at the crystallization temperature (110 degrees C) were eroded
      from the crystallographic a-axis to show splintered morphologies at the tips of
      the crystals. In some cases, lamellar crystals were hydrolyzed from the
      crystallographic b-axis, resulting in the formation of small crevices. These
      results suggest that disordered molecular chain-packing regions exist in the
      crystal along the crystallographic a- and b-axes, and that enzymatic degradation
      predominantly occurs from these defective regions. In addition, cantilever-tip
      induced enzymatic degradation was carried out in the presence of PHB
      depolymerase. A concave area was artificially formed on the stacked lamellar
      crystals by the AFM tip. In-situ AFM observation has revealed that enzymatic
      degradation proceeds along both the longitudinal and lateral directions of the
      lamellae. At the same time, the PHB depolymerase preferentially eroded the
      concave area along the crystallographic c-axis. These results demonstrated that
      the PHB depolymerase predominantly degrades the less-ordered molecular chain
      packing regions in the crystals.

PMID- 15468219
TI  - Biodegradable polyesters reinforced with surface-modified vegetable fibers.
AB  - Flax fibers are investigated as reinforcing agents for biodegradable polyesters
      (Bionolle and poly(lactic acid) plasticized with 15 wt.-% of acetyltributyl
      citrate, p-PLLA). The composites are obtained either by high temperature
      compression molding fiber mats sandwiched between polymer films, or by batch
      mixing fibers with the molten polymer. Fibers in composites obtained by the
      latter method are much shorter (140-200 microm) than those of the mats (5,000
      microm). Flax fibers are found to reinforce both p-PLLA and Bionolle (i.e.
      tensile modulus and strength increase) when composites based on fiber mats are
      investigated. Conversely, analogous composites obtained by batch mixing show poor
      mechanical properties. The observed behavior is attributed to the combined effect
      of fiber length and fiber-matrix adhesion. If flax fibers with a modified surface
      chemistry are used, the strength of short fiber composites is seen to improve
      significantly because the interface strengthens and load is more efficiently
      transferred. Appropriate surface modifications are performed by heterogeneous
      acylation reactions or by grafting poly(ethylene glycol) chains (PEG, molecular
      weight 350 and 750). The highest tensile strength of p-PLLA composites is reached
      when PEG-grafted flax fibers are used, whereas in the case of Bionolle the best
      performance is observed with acylated fibers.

PMID- 15468220
TI  - Crystal structure, thermal behavior and enzymatic degradation of
      poly(tetramethylene adipate) solution-grown chain-folded lamellar crystals.
AB  - Solution-grown chain-folded lamellar single crystals of poly(tetramethylene
      adipate) (PTMA) were prepared from a dilute solution of 2-methyl-1-propanol by
      isothermal crystallization. PTMA crystals were hexagonal-shaped and polyethylene
      decoration of the crystals resulted in a "six cross-sector" surface morphology
      and showed that the average direction of chain folding is parallel to the crystal
      growth planes of [110] and [010]. Chain-folded lamellar crystals gave well
      resolved electron diffraction diagrams corresponding to all the equatorial
      reflections of the X-ray fiber diagram obtained from stretched PTMA melt-quenched
      film (beta structure). The unit cell parameters of the beta structure of PTMA
      were determined as a = 0.503 nm, b = 0.732 nm and c (fiber axis) = 1.442 nm with
      an orthorhombic crystal system. The fiber repeat distance is appropriate for an
      all-trans backbone conformation for the straight stems. The setting angle, with
      respect to the a axis, is +/-46 degrees for the corner and center chains. Thermal
      behavior of lamellar crystals has been investigated by means of transmission
      electron microscopy (TEM) and atomic force microscopy (AFM). The lamellar
      thickness at the edges of the crystal increased after thermal treatment with
      taking the molecular chains into recrystallization parts; the holes then opened
      up at the thickening front of the crystal. The morphological changes of lamellar
      crystals after enzymatic degradation by Lipase type XIII from Pseudomonas sp. and
      water-soluble products were characterized by TEM, AFM, gel permeation
      chromatography, high performance liquid chromatography and fast atom bombardment
      mass spectrometry. The degradation progressed mainly from the edges of the
      lamellar crystals without decreasing the molecular weights and the lamellar
      thicknesses. The central portion of single crystals was often degraded by
      enzymatic attacks. This result combined with thermal behavior indicates that the
      loosely chain-packing region exists inside the single crystal, and that molecular
      chains in this region have higher mobility against thermal and enzymatic
      treatments.

PMID- 15468221
TI  - Erosion induced controllable release of gliclazide encapsulated inside degradable
      polymeric particles.
AB  - The microphase inversion of water-insoluble poly(L-lactide), "poly[(L-lactide)-co
      glycolide] and polylactide-block-poly(ethylene oxide)-block-polylactide from THF
      to water can result in narrowly distributed stable particles. Gliclazide, a
      commercial drug, can be encapsulated inside during the process. The formation and
      degradation of such particles was studied by laser light scattering. In
      comparison with the corrosion of a bulk material, the degradation of each
      particle is so fast that we only detect the decrease of the particle number, not
      the corrosion of individual particles. Therefore, the degradation is a "one-by
      one" random process, just like the chemical reaction of molecules in solution.
      The disappearing rate of the particle number is nearly independent of time, ideal
      for the controlled release of drugs encapsulated inside. The amount of
      encapsulated gliclazide depends on the copolymer's hydrophobicity (composition),
      while the releasing rate mainly is, directly related to the disappearing rate of
      the particles. The correlation between the fluorescence intensity and the
      degradation was used to study the kinetics of gliclazide releasing. The releasing
      pattern is controllable with a proper choice of the drug loading, copolymer
      composition, pH and temperature.

PMID- 15468222
TI  - Involvement of Hevea latex organelle membrane proteins in the rubber biosynthesis
      activity and regulatory function.
AB  - Centrifugation of fresh Hevea rubber latex yields three distinct fractions. The
      sediment bottom fraction (BF) content of membrane-bound organelles is ca. 20 vol.
      % of latex. Prolonged storage or delayed use of fresh latex will result in
      disintegration and loss of the bottom fraction. This is due to the osmotically
      sensitive BF rupture and its membrane debris being tightly bound to the top
      rubber particles (RP) phase. The BF membrane was found to be highly active for
      rubber biosynthesis (RB), in contrast to previous reports that describe RB only
      occurring on the RP surface. It was clearly shown that washed BF membrane (WBM)
      was much more active than fresh RP for RB activity. WBM was highly activated by
      SDS for RB in a biphasic manner, but SDS strongly inhibited the RP. Probably WBM
      micelle formation resulted in a highly increased active surface area for RB. C55
      PP (UPP) was a very active allylic for WBM in RB function, but inactive for RP.
      Serial acetone extraction of WBM proteins showed a distinct profile of the
      fractions with different RB activity. WBM isolated proteins suspended in 2%
      sodium dodecyl sulfate (SDS) with an RB activity equal to that of intact WBM was
      with the 20% acetone protein fraction. The 60 and 80% fractions were inactive.
      Combining the 20 with 80% fractions showed a complete inhibition of RB activity.
      Complete RB loss was also found when WBM was mixed with the 80% fraction,
      indicating that WBM has both an enzyme system and a factor for regulation of the
      RB activity in a well controlled metabolic function for the latex RB process.

PMID- 15468223
TI  - Biodegradable water absorbent synthesized from bacterial poly(amino acid)s.
AB  - Biodegradable hydrogels prepared by gamma-irradiation from microbial poly(amino
      acid)s have been studied. pH-Sensitive hydrogels were prepared by the gamma
      irradiation of poly(gamma-glutamic acid) (PGA) produced by Bacillus subtilis and
      poly(epsilon-lysine) (PL) produced by Streptomyces albulus in aqueous solutions.
      When the gamma-irradiation dose was 19 kGy or more, and the concentration of PGA
      in water was 2 wt.-% or more, transparent hydrogels could be produced. For the 19
      kGy dose, the produced hydrogel was very weak, however, the specific water
      content (wt. of absorbed water/wt. of dry hydrogel) of this PGA hydrogel was
      approximately 3,500. The specific water content decreased to 200, increasing when
      the gamma-irradiation dose was over 100 kGy. Under acid conditions or upon the
      addition of electrolytes, the PGA hydrogels shrunk. The PGA hydrogel was pH
      sensitive and the change in the volume of the hydrogel depended on the pH value
      outside the hydrogel in the swelling medium. This PGA hydrogel was
      hydrodegradable and biodegradable. A new novel purifier reagent (coagulant), made
      from the PGA hydrogels, for contaminated turbid water has been found and
      developed by Japanese companies. A very small amount of this coagulant (only 2
      ppm in turbid water) with poly(aluminum chloride) can be used for the
      purification of turbid water. A PL aqueous solution also can change into a
      hydrogel by gamma-irradiation. The specific water content of the PL hydrogel
      ranged from 20 to 160 depending on the preparation conditions. Under acid
      conditions, the PL hydrogel swelled because of the ionic repulsion of the
      protonated amino groups in the PL molecules. The rate of enzymatic degradation of
      the respective PL hydrogels by a neutral protease was much faster than the rate
      of simple hydrolytic degradation.

PMID- 15468224
TI  - Enzymatic hydrolysis of alpha- and beta-oligo(L-aspartic acid)s by poly(aspartic
      acid) hydrolases-1 and 2 from Sphingomonas sp. KT-1.
AB  - The enzymatic hydrolysis of alpha- and beta-oligo(L-aspartic acid)s by PAA
      hydrolase-1 and PAA hydrolase-2 (purified from Sphingomonas sp. KT-1) was
      performed to elucidate the mechanism of the microbial degradation by Sphingomonas
      sp. KT-1 of the thermally synthesized alpha,beta-poly(D,L-aspartic acid) (tPAA).
      GPC analysis of the hydrolyzed products of alpha- and beta-tetra(L-aspartic
      acid)s by PAA hydrolase-1 has showed that PAA hydrolase-1 is capable of
      hydrolyzing only the specific amide bonds between beta-aspartic acid units. The
      RP-HPLC analysis of the enzymatic hydrolysis of beta-oligo(L-aspartic acid)s (4
      and 5 mers) by PAA hydrolase-1 has suggested that the enzymatic hydrolysis of
      beta-oligo(L-aspartic acid)s occurs via an endo-mode cleavage. In contrast, PAA
      hydrolase-2 hydrolyzed both alpha- and beta-oligo(L-aspartic acid)s via an exo
      mode cleavage to yield L-aspartic acid as a final product. A kinetic study on the
      enzymatic hydrolysis of alpha-oligo(L-aspartic acid)s (3 to 7 mers) by PAA
      hydrolase-2 has indicated that Km values are almost independent of the number of
      monomer units in oligomers of 4 to 7 mers, while that Vmax values are markedly
      dependent on the chain length and show a maximum value at 5 mer.

PMID- 15468225
TI  - Ring-opening polymerization of L-lactide and preparation of its microsphere in
      supercritical fluids.
AB  - The ring-opening polymerization of L-lactide initiated by stannous octoate was
      carried out in supercritical chlorodifluoromethane (scR22) at various reaction
      conditions (time and temperature) and reactant concentrations (initiator,
      monomer, and solvent). The monomer conversion increased to ca. 70% on increasing
      the reaction time to 1 h. The molecular weight of the poly(L-lactide) (PLLA)
      product also increased to ca. 160,000 g x mol(-1) over the same period.
      Increasing reaction temperature from 90 to 130 degrees C resulted in increased
      monomer conversion and PLLA molecular weight. A series of polymerizations
      conducted at various 1-dodecanol and stannous octoate concentrations suggested
      that stannous octoate does not act as an initiator by itself, and that the tin
      alkoxide formed from 1-dodecanol and stannous octoate serves as the initiating
      species in scR22. While enhancements of the monomer conversion and PLLA molecular
      weight were observed with increasing monomer concentration, the
      chlorodifluoromethane concentration had the opposite on both. After the
      polymerization, PLLA microspheres were prepared in situ by using a continuous
      supercritical antisolvent process without residual organic solvent and monomer to
      yield highly purified microspheres for environmental and biomedical applications.

PMID- 15468226
TI  - Lipase-catalyzed transformation of poly(lactic acid) into cyclic oligomers.
AB  - Enzymatic transformations into cyclic oligomers were carried out with the
      objective of developing chemical recycling of poly(lactic acid)s, such as
      poly(D,L-lactic acid) (PDLLA), poly(D-lactic acid) (PDLA) and poly(L-lactic acid)
      (PLLA), which are typical biodegradable polymers. They were degraded by lipase in
      an organic solvent to produce the corresponding cyclic oligomer with a molecular
      weight of several hundreds. PDLLA (with a Mw of 84,000) was quantitatively
      transformed into cyclic oligomers by lipase RM (Lipozyme RM IM) in
      chloroform/hexane at 60 degrees C. PLLA (with a Mw of 120,000) was transformed
      into cyclic oligomer by lipase CA (Novozym 435) at a higher temperature of 100
      degrees C in o-xylene. The oligomer structure was identified by 1H and 13C NMR
      spectroscopy and MALDI-TOF (matrix assisted laser desorption/ionization-time-of
      flight) mass spectrometry.

PMID- 15468227
TI  - Organic-inorganic hybrids from renewable plant oils and clay.
AB  - This study deals with the preparation and properties of a new class of organic
      inorganic hybrids from renewable resources. The hybrids were synthesized by an
      acid-catalyzed curing of epoxidized triglycerides in the presence of an
      organophilic montmorillonite (a modified clay). The mechanical properties were
      improved by the incorporation of clay in the oil-based polymer matrix. The
      reinforcement effect due to the addition of clay was confirmed by dynamic
      viscoelasticity analysis. The hybrids showed relatively high thermal stability.
      The co-curing of epoxidized soybean and linseed oils in the presence of clay
      produced hybrids with controlled mechanical and coating properties. The barrier
      property of the hybrid towards water vapor was superior to that of the oil
      polymer. The development of the present hybrids consisting of inexpensive
      renewable resources, triglyceride and clay is expected to contribute to global
      sustainability.

PMID- 15468228
TI  - Hydrogel formation between enantiomeric B-A-B-type block copolymers of
      polylactides (PLLA or PDLA: A) and polyoxyethylene (PEG: B); PEG-PLLA-PEG and PEG
      PDLA-PEG.
AB  - A mixed suspension of the enantiomeric B-A-B triblock copolymers, polyoxyethylene
      block-poly(L-lactide)-block-polyoxyethylene (PEG-PLLA-PEG) and polyoxyethylene
      block-poly(D-lactide)-block-polyoxyethylene (PEG-PDLA-PEG), was found to induce
      reversible gel-to-sol transition depending on the polymer concentration and
      temperature. The storage and loss moduli of the gel formed at lower temperature
      were much higher than those of the gel prepared from the corresponding ABA-type
      triblock copolymers because of the higher polymer concentration in the former.
      Although the stereo-complexation of the PLLA and PDLA blocks occurred at higher
      temperature also in the B-A-B copolymers, it was not responsible for the gelation
      of the mixed suspension. The PEG chains, involved in the helix formation of the
      PLLA and PDLA, should form helices with opposite helical senses to aggregate and
      lead the gelation of the system.

PMID- 15468229
TI  - Peptide/protein hybrid materials: enhanced control of structure and improved
      performance through conjugation of biological and synthetic polymers.
AB  - The conjugation of peptides/proteins and synthetic polymers is a useful strategy
      to overcome some of the limitations related to the use of the individual
      components. This review will highlight two aspects: enhanced structural control
      at the nanometer level and improved performance, in particular with respect to
      biomedical applications. In the former case, peptide sequences are mainly used to
      mediate self-assembly of synthetic polymers. In the latter case, conjugation of
      an appropriate synthetic polymer to a pharmaceutically active peptide/protein
      can, for example, prevent premature enzymatic degradation and enhance blood
      circulation times, which is therapeutically advantageous.

PMID- 15468230
TI  - The biodeterioration of synthetic resins used in conservation.
AB  - Synthetic resins have been extensively employed by artists in their works of art,
      e.g. as paint binders, or by conservators for conservation treatments, e.g. as
      stone consolidants and protectives. It is generally thought that synthetic resins
      are less prone to chemical, physical and biological deterioration than other
      organic products but there are many articles in the scientific literature and
      some reports in the conservation of cultural heritage literature claiming that
      microorganisms are capable of degrading synthetic resins. This paper reviews the
      researches on the biodeterioration of synthetic resins used in the conservation
      of cultural heritage, including stone, painting and textile materials, carried
      out in the last fifty years.

PMID- 15468231
TI  - Preparation and thermosensitivity of naturally occurring polypeptide poly(gamma
      glutamic acid) derivatives modified by propyl groups.
AB  - Poly(gamma-glutamic acid) (gamma-PGA) is a biosynthetic polymer, and the carboxyl
      groups are able to undergo a chemical modification. In this study, poly(alpha
      propyl gamma-glutamate) (gamma-PGA propylate) was synthesized by the
      esterification of these carboxyl groups to yield a thermosensitive and
      biodegradable polymer. In aqueous solution, the gamma-PGA propylate can impart
      thermosensitivity by controlling the hydrophobic-hydrophilic balance of the gamma
      PGA polymeric chains.

PMID- 15468232
TI  - Fabrication of temperature-sensitive imprinted polymer hydrogel.
AB  - Weakly cross-linked temperature sensitive gels that memorize 4-aminopyridine
      molecules were designed and synthesized. The polymer gels show special
      selectivity, good thermo-sensitivity and reusability, which would have an
      enormous potential of application in drug controlled release systems.

PMID- 15468233
TI  - Synthesis of nanosized chitosan-poly(acrylic acid) particles by a dropping
      method.
AB  - Deoxyribonucleic acid (DNA) vaccines are being investigated extensively because
      of their excellent potential over conventional protein ones. A suitable DNA
      carrier, consisting of uniformly dispersed chitosan-poly(acrylic acid) particles
      with an average size of 30 nm, was successfully synthesized by a dropping method
      with a ratio of chitosan solution to poly(acrylic acid) solution of 1:1 and was
      incubated in a buffer solution with a pH value of 3.0. The particle size
      increased from 35.76 to 45.90 nm when the pH value of the buffer solution was
      increased from 3.0 to 7.4. After freeze-drying, the non-incubated mixed solution
      showed a membranous morphology. A powdered product was formed from the mixed
      solution as incubated in buffer solution with pH values of 3.0 and 5.3. However,
      when the mixed solution was incubated in a buffer solution of pH 7.4, a mixture
      of membrane and powder was obtained.

PMID- 15468234
TI  - Chiral polymers containing a carbohydrate moiety: synthesis.
AB  - This paper reports the preparation of poly(acetal-ethers) by two alternative
      synthetic pathways (alkaline and acid-catalyzed conditions). Polycondensations of
      methyl 2,3:4,6-di-O-salicylidene-alpha-D-mannopyranoside (3) (mixtures of endo-H
      and exo-H dioxolan-2-yl-diastereomers) with 1,4-dibromobutane (4) (method I a and
      I b) were performed in solvents (DMF, butyl acetate/DMF, DMSO) and were catalyzed
      by K2CO3/KI or KOH. A similar polymer (6) was formed by the reaction of methyl
      alpha-D-mannopyranoside (1) and 1,4-bis(2-formylphenoxy)butane (7), catalyzed by
      p-toluenesulfonic acid (method II). Regardless of conversion or initial comonomer
      feed ratios, the composition of the polycondensates depended on the reaction
      conditions, leading to the formation of macrocyclic [1 + 1] (5) and [2 + 2]
      compounds, which were macromolecules with diverse molecular weights and optical
      properties. The regioselective polycondensation was examined by 1H NMR
      spectroscopy of selected polymers. In the case of 5-membered cyclic acetal units,
      mixtures of the endo-H and exo-H dioxolan-2-yl system, diastereomers were formed
      in the polymer chain. The macrocycles and linear oligomers were identified by NMR
      and electrospray mass spectrometry (ESI-MS). Thermodynamically controlled
      reactions for making macrocycles as well as oligomers in the absence of templates
      are also discussed.

PMID- 15468235
TI  - New hydrolyzable pH-responsive cationic polymers for gene delivery: a preliminary
      study.
AB  - Here we want to report the synthesis and the characterization of 2-methylacrylic
      acid 2-(3-imidazol-1-yl-propionyloxy)ethyl ester (IPEMA), a new methacrylate
      derivative monomer bearing an hydrolyzable side chain terminated by an imidazole
      group. The kp/kt(1/2) value for its homopolymerization in N,N-dimethylformamide
      at 60 degrees C was found to be 0.120 mol(-1/2) x L(1/2) x s(-1/2). The free
      radical copolymerization of N,N-dimethylaminoethyl methacrylate and this monomer
      was studied in N,N-dimethylformamide at 60 degrees C, the reactivity ratios of
      this couple of monomers were determined to be r(DMAEMA) = 1.13 +/- 0.09 and
      r(IPEMA) = 0.82 +/- 0.09 (using distinct calculation methods). Molecular weights
      analysis, parallely with refractive index increments measurements, were performed
      to characterize the obtained polymers. Potentiometric titrations showed the
      ability of these copolymers to act as a 'proton sponge'. Preliminary study of the
      copolymers hydrolysis proved that imidazole units could be slowly cleaved from
      the polymer backbone at 37 degrees C in neutral aqueous buffer. Agarose gel
      electrophoresis of plasmid DNA/polymer complexes demonstrated the DNA complexing
      properties of these imidazole-based copolymers.

PMID- 15468236
TI  - Amphiphilic block copolymers based on poly(2-acryloyloxyethyl phosphorylcholine)
      prepared via RAFT polymerisation as biocompatible nanocontainers.
AB  - Amphiphilic block copolymers composed of poly(butyl acrylate) and poly(2
      acryloyloxyethyl phosphorylcholine) have been prepared using reversible addition
      fragmentation transfer (RAFT) polymerisation. The conversion of the
      polymerisation was determined using online FT NIR spectroscopy. NMR spectroscopy
      was used not only to support the results obtained from FT NIR spectroscopy but
      also prove the formation of micelles. Due to the strong aggregation tendency of
      these block copolymers and the resulting difficulties concerning the molecular
      weight analysis test experiments were carried out replacing poly(2
      acryloyloxyethyl phosphorylcholine) with poly(2-hydroxyethyl acrylate). Micelle
      size and the aggregation behaviour were investigated using dynamic light
      scattering. The sizes of the nanocontainers obtained were found to be influenced
      by the block length as well as the solvent leading to micelles in the range
      between 40 and 160 nm. The toxicity of the RAFT agent used was then analysed by
      cell growth inhibition tests.

PMID- 15468237
TI  - Sustained release of BSA from a novel drug delivery matrix -- bullfrog skin
      collagen film.
AB  - A novel drug delivery system, bullfrog skin collagen film, was employed to
      release bovine serum albumin (BSA). The biophysical properties of bullfrog skin
      collagen film used were evaluated by thermal denaturation temperature and
      percentage water loss. The film obtained exhibited good stability and can be
      taken as a good candidate for drug delivery matrix. Compared with conventional
      collagen from molecular weight and amino acid composition, bullfrog skin collagen
      showed significant differences. For safety considerations, bullfrog skin collagen
      has great advantages. The release kinetics of BSA from bullfrog skin collagen
      film was measured in vitro. The results indicated bullfrog skin collagen film
      could be used for sustained release of BSA. Thus, bullfrog skin collagen film can
      be taken as a novel drug delivery system.

PMID- 15468238
TI  - Encapsulation and/or release behavior of bovine serum albumin within and from
      polylactide-grafted dextran microspheres.
AB  - Polylactide (PLA)-grafted dextran (Dex-graft-PLA) of various contents of sugar
      units was synthesized by anionic polymerization of L-lactide (L-LA) using the
      alkoxide of partially trimethylsilylated dextran (TMSDex) and subsequently
      removing the trimethylsilyl (TMS) groups. The copolymer showed different
      solubility from L-LA homopolymer with increasing the content of sugar units. We
      prepared bovine serum albumin (BSA)-loaded microspheres (MS)s according to a
      water-in-oil-in-water emulsion-solvent evaporation/extraction method using
      methylene chloride/DMSO as an organic cosolvent. MSs prepared from Dex-graft-PLA
      [MS(Dex-graft-PLA)s] exhibited higher loading efficiency of BSA than MSs prepared
      from PLLA [MS(PLLA)s]. The in vitro release rate of BSA from MS(Dex-graft-PLA)
      was faster than that from MS(PLLA). BSA released from MS(Dex-graft-PLA)
      maintained the secondary structure of native BSA to a great extent, compared with
      BSA released from MS(PLLA).

PMID- 15468239
TI  - Enhanced biocompatibility in biostable poly(carbonate)urethane.
AB  - In this work, we synthesized two MDI-based polyurethanes, including a
      poly(ether)urethane (PEU) and a poly(carbonate)urethane (PCU), by using different
      soft segments, poly(tetramethylene oxide) and poly(hexyl, ethyl)carbonate diol (M
      approximately 2,000). We demonstrated that, in addition to the enhanced
      biostability of PCU over PEU, the biological performances of PCU in vitro were
      also improved in general. These included, better cellular attachment and
      proliferation, less platelet activation, as well as reduced monocyte activation.
      The unusual wide-ranging enhancement in biocompatibility for PCU was believed to
      be related to the larger micro-phase separation in PCU (approximately 25 nm) that
      caused distinct protein adsorption on the surface. The total number of adherent
      monocytes (nonactivated and activated) on the bare sample surfaces, albumin pre
      adsorbed sample surfaces, and fibrinogen pre-adsorbed sample surfaces.

PMID- 15468240
TI  - Mucin macromolecules in normal, adenomatous, and carcinomatous colon: evidence
      for the neotransformation.
AB  - Mucins are high molecular-weight glycoproteins having oligosaccharides attached
      to serine or threonine residues of the mucin core protein backbone by O
      glycosidic linkages. They are major components of mucus, covering the luminal
      surfaces of epithelial respiratory, gastrointestinal and reproductive tracts, and
      responsible for its viscoelastic properties. The core proteins of mucins are
      encoded by different mucin genes. Aberrations in the cell surface carbohydrates
      including mucins have been regarded as a universal characteristic of the
      malignant transformation of cells. These alterations are considered to be
      relevant to the abnormal behaviour of cancer cells, such as altered cell adhesion
      or metastasis, and to the avoidance of immunological defence.

PMID- 15468241
TI  - Peroxidase-catalyzed oxidative polymerization of phenol with a nonionic polymer
      surfactant template in water.
AB  - Peroxidase-catalyzed oxidative polymerization of phenol has been examined using
      the template, poly(ethylene glycol) monododecyl ether (PEGMDE), in water. The
      role of this template, which forms a complex with phenol in the polymerization,
      was verified by UV measurements. During the reaction, a complex of the resulting
      polymer and PEGMDE was precipitated in high yields. The amount and the PEG chain
      length of PEGMDE strongly affected the polyphenol yield. The unit molar ratio of
      polyphenol and PEG of the template was about 1:0.9. The presence of the PEGMDE
      template in the aqueous medium greatly improved the regioselectivity of the
      polymerization, yielding polyphenol with a phenylene unit content close to 90%.
      FT-IR, DSC, and XRD analyses confirmed the formation of the miscible complex of
      polyphenol and PEGMDE by hydrogen-bonding interactions.

PMID- 15468242
TI  - Synthesis of enzymatically crosslinkable peptide-poly(L-lysine) conjugate and
      creation of bio-inspired hybrid fibers.
AB  - Poly(L-lysine)s having an Nepsilon-substituted tetrapeptide, Lys-Gly-Tyr-Gly,
      were synthesized by the coupling of the protected tetrapeptide active ester, Boc
      Lys(Z)-Gly-Tyr(Bzl)-Gly (4-hydroxyphenyl)dimethylsulfonium methylsulfate and
      Nepsilon-group of the poly(L-lysine) side chain. The Nepsilon-substituted
      tetrapeptide functions as the substrate of tyrosinase and is responsible for the
      enzyme-mediated interpolymer cross-linking. The degree of Nepsilon-substitution
      (DS) was mostly controlled by changing the stoichiometry between the Nepsilon
      amino groups of the parent poly(L-lysine) and the protected tetrapeptide active
      ester. Two kinds of samples having DS values of 8.6 and 18 mol-% were prepared.
      The resulting cationic Nepsilon-(Lys-Gly-Tyr-Gly)-poly(L-lysine) (abbreviated as
      PLL(GYGK)) was spun into hybrid fibers with the anionic polysaccharide gellan via
      a polyionic complexation reaction at the interface between aqueous solutions of
      the two polymers. The mechanical strengths of the PLL(GYGK)-gellan hybrid fibers
      were superior to those of the original poly(L-lysine)-gellan fibers. The
      mechanical strength of the hybrid fibers further increased upon the tyrosinase
      mediated cross-linking reaction of the PLL(GYGK). This result indicates that the
      covalent cross-bridge formation between the Nepsilon-substituted peptides
      significantly contributed to reinforcement of the hybrid fibers. The present
      study affords a new methodology for reinforcement inspired by a biological
      process.

PMID- 15468243
TI  - Surface-grafted polystyrene beads with comb-like poly(ethylene glycol) chains:
      preparation and biological application.
AB  - We prepared surface-grafted polystyrene (PS) beads with comb-like poly(ethylene
      glycol) (PEG) chains. To accomplish this, conventional gel-type PS beads (35-75
      microm) were treated with ozone gas to introduce hydroperoxide groups onto the
      surface. Using these hydroperoxide groups, poly(methyl methacrylate) (PMMA, Mn=
      22,000-25,000) was grafted onto the surface of the PS beads. The ester groups of
      the grafted PMMA were reduced to hydroxyl groups with lithium aluminum hydride
      (LAH). After adding ethylene oxide (EO) to the hydroxyl groups, we obtained the
      PS-sg-PEG beads, which had a rugged surface and a diameter of 80-150 microm. We
      could obtain several kinds of the PS-sg-PEG beads by controlling the chain
      lengths of the grafted PMMA and the molecular weights of the PEG chains. The
      grafted PEG layer was about 30-50 microm thick, which was verified from the cross
      sectioned views of the fluorescamine-labeled beads. These fluorescence images
      proved that the beads possessed a pellicular structure. Furthermore, we found
      that the surface-grafted PEG chains had the characteristic property of reducing
      non-specific protein adsorption on the beads.

PMID- 15468244
TI  - Binding of the bioactive component daphnetin to human serum albumin demonstrated
      using tryptophan fluorescence quenching.
AB  - Daphnetin (7,8-dihydroxycoumarin), one of the major bioactive components isolated
      from Daphne koreane Nakai, has been used in traditional Chinese medicine for the
      treatment of coagulation disorders. It is also a chelator, an antioxidant and a
      protein kinase inhibitor. In this paper, a combination of intrinsic fluorescence,
      Fourier transform infrared (FT-IR) spectroscopy and circular dichroic (CD)
      spectroscopy has been used to characterize the binding between daphnetin and
      human serum albumin (HSA) under physiological conditions with drug concentrations
      of 6.7 x 10(-6) - 2.3 x 10(-5) mol x L(-1), and a HSA concentration of 1.5 x 10(
      6) mol x L(-1). Changes in the CD spectra and FT-IR spectra were observed upon
      ligand binding, and the degree of tryptophan fluorescence quenching did change
      significantly in the complexes. These data have proved the change in protein
      secondary structure accompanying ligand binding. The change in tryptophan
      fluorescence intensity was used to determine the binding constants. The
      thermodynamic parameters, the enthalpy change (DeltaH) and the entropy change
      (DeltaS) were calculated to be -12.45 kJ x mol(-1)and 52.48 J x mol(-1) x K(-1)
      according to the van't Hoff equation, which indicated that hydrophobic and
      electrostatic interactions played the main role in the binding of daphnetin to
      HSA, in accordance with the results of calculations performed on a Silicon
      Graphics Ocatane2 workstation. In addition, the binding distance between
      daphnetin and HSA was obtained (4.02 nm) based on the Forster energy transfer
      theory.

PMID- 15468245
TI  - Polyelectrolyte complex films derived from polyethyleneoxide-maleic acid
      copolymer and chitosan: preparation and characterization.
AB  - Polyelectrolyte complex films were prepared with polyethyleneoxide-maleic acid
      copolymer and chitosan using a casting/solvent evaporation method. The films were
      examined in terms of their IR spectra, surface and cross-section morphologies,
      cytotoxicity, and swelling behavior at different pH levels. To assess the
      potential of these films as a biomedical device, the profiles of the release of
      model drug from the CS/PEOMA films were examined at pH 4.8. The surface
      morphology of the films was quite smooth and uniform, and the cross-sectional
      morphology was dense and homogeneous. The swelling behaviors of CS/PEOMA films
      were found to depend on the pH of the solution as well as on the CS/PEOMA
      composition. Drug release from different CS/PEOMA films at pH 4.8 was found to be
      dependent on film composition. The results showed the potential applicability of
      CS/PEOMA film as a drug delivery vehicle.

PMID- 15468246
TI  - Na+ and Mg2+ ion effect on the stability of a poly I . poly A . poly I triple
      helix.
AB  - Differential UV spectroscopy was used to study the temperature dependence of the
      conformational equilibrium in aqueous poly I . poly A . poly I (A2I) solutions
      containing Na+ (0.1-2 M) and Mg2+ (10(-5)-0.005 M) ions. Over the whole range of
      the studied Na+ and Mg2+ concentrations, the heating-induced destruction of the
      triple A2I helix is actually the A2I --> A + I + I (3 --> 1) transition. The rise
      of the transition temperature with increasing Na+ and Mg2+ contents is well
      described by Manning's and the "ligand" theories, which makes it possible to
      estimate the linear charge density on the single-stranded poly I (xi = 1.9 +/-
      0.1) and the Mg2+-A2I binding constant (K = 1,250 M(-1) for the zero degree of
      binding). An analytical expression has been obtained, which correlates the
      constants of Mg2+ binding to three- and single-stranded polynucleotides (K3 and
      K1, respectively) and the linear charge density on them. There are only minor
      distinctions between the K3 values for A2U and A2I because these polynucleotides
      have similar structures. The difference in the K1 values is also slight as single
      stranded poly U, poly I, and poly A have similar conformations. Dependence of the
      conformational transition temperatures of two triple helices with changing Mg2+
      concentration.

PMID- 15468247
TI  - The sustainability of NatureWorks polylactide polymers and Ingeo polylactide
      fibers: an update of the future.

PMID- 15468248
TI  - Synthesis of AB diblock copolymers by atom-transfer radical polymerization (ATRP)
      and living polymerization of alpha-amino acid-N-carboxyanhydrides.
AB  - The synthesis of poly(methyl acrylate)-block-poly(gamma-benzyl-L-glutamate) (PMA
      b-PBLG) diblock copolymers, using atom-transfer radical polymerization (ATRP) of
      methyl acrylate and living polymerization of gamma-benzyl-L-glutamate-N
      carboxyanhydride (Glu-NCA) is described. Amido-amidate nickelacycle end groups
      were incorporated onto amino-terminated poly(methyl acrylates), and the resulting
      complexes were successfully used as macroinitiators for the growth of polypeptide
      segments. This method allows the controlled preparation of polypeptide-block
      poly(methyl acrylate) diblock architectures with control over polypeptide chain
      length and without the formation of homopolypeptide contaminants.

PMID- 15468249
TI  - Helical polymer carrying helical grafts from peptide-based acetylene
      macromonomers: synthesis.
AB  - N-Propargylamide-terminated peptide-based macromonomers with a degree of
      polymerization ranging from 4 to 40 were synthesized by the polymerization of
      gamma-benzyl and gamma-stearyl-L-glutamate-N-carboxy anhydrides initiated with
      propargylamine. The macromonomers took an alpha-helical structure, which was
      confirmed by signals at 208 and 220 nm in CD spectra. The macromonomers were
      subjected to polymerization and copolymerization with an alanine-derived N
      propargylamide [N-(tert-butoxycarbonyl)-L-alanine-N'-propargylamide] catalyzed
      with (2,5-norbornadiene)Rh+[eta6-C6H5B- (C6H5)3]. It was confirmed through a CD
      spectroscopic study that the copolymer obtained from the copolymerization of the
      gamma-stearyl-L-glutamate-based macromonomer with the alanine-derived N
      propargylamide had a helical polyacetylene main chain and helical polypeptide
      side chains.

PMID- 15468250
TI  - Temperature-sensitive polyamidoamine dendrimer/poly(N-isopropylacrylamide)
      hydrogels with improved responsive properties.
AB  - Novel temperature-sensitive poly(N-isopropylacrylamide)/amine-terminated
      polyamidoamine dendrimer G6-NH2 hydrogels with fast responsive properties were
      synthesized by forming semi-interpenetrating polymeric networks. In contrast to
      the conventional PNIPA hydrogel, these new gels showed rapid shrinking rate at
      the temperature above lower critical solution temperature (LCST), and exhibited
      higher equilibrium swelling ratio at room temperature. All these properties might
      be attributed to the incorporation of polyamidoamine dendrimer G6-NH2, which
      forms water-releasing channels and increases the hydrophilicity of PNIPA network.
      The novel hydrogels have potential applications in drug and gene delivery.

PMID- 15468251
TI  - Hydrophilic polymer drug from a derivative of salicylic acid: synthesis,
      controlled release studies and biological behavior.
AB  - Hydrophilic polymeric drugs bearing "Triflusal" (4-trifluoromethylsalicylic
      acid), a drug widely used as antithrombogenic agent (Disgren), have been prepared
      by free radical copolymerization of methacryloyloxyethyl [2-(acetyloxy)-4
      (trifluoromethyl)] benzoate (HTRF) and N,N'-dimethylacrylamide (DMA). The
      reactivity ratios of both monomers have been determined by 1H NMR spectra by
      applying non-linear least square treatments to the copolymerization equation
      (terminal model), and the kinetic parameters obtained indicated that the
      microstructure of copolymer chains is homogeneous, with a random distribution of
      the active HTRF units along the copolymer chains. That means that for the
      copolymer system THDMA22 used in this work, HTRF units are mainly isolated in
      relatively long DMA sequences. Therefore, in this structure the intramolecular
      interactions between adjacent HTRF units are negligible. Release of Triflusal
      from THDMA22 has been studied in vitro using buffered solutions at pH = 2, 7.4
      and 10 and 37 degrees C. The system showed an interesting pseudo-zero order
      release profile at pH = 7.4 during several months. It has been also evaluated the
      pharmacological activity and the behavior of the system in contact with
      biological media. In this sense, we have carried out some in vitro studies about
      the antiaggregant properties and biocompatibility of THDMA22. Results demonstrate
      that this copolymer inhibits platelet aggregation in its macromolecular form and
      presents a good biocompatibility with Human Osteoblastic Cells (HOS).

PMID- 15468252
TI  - Lipase catalyzed copolymerization of 3(S)-isopropylmorpholine-2,5-dione and D,L
      lactide.
AB  - The polymerization and copolymerization of 3(S)-isopropylmorpholine-2,5-dione
      (IPMD) and D,L-lactide (DLLA) were carried out in the presence of Porcine
      pancreatic lipase type II (PPL) as a catalyst at 100 degrees C for 168 h.
      Homopolymers and random copolymers of various compositions were obtained with a
      carboxylic acid group at one end and a hydroxyl group at the other end. The glass
      transition temperature of the copolymers decreases with increasing mole fraction
      of DLLA residue in the copolymers.

PMID- 15468253
TI  - PHEMA hydrogels obtained by a novel low-heat curing procedure with a potential
      for in situ preparation.
AB  - In this work, we report on poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels
      obtained by a low heat curing reaction. These materials are suitable for in situ
      preparation and therefore endowed with a potential for several biomedical
      applications. The novel procedure adopted involves as the first step the
      synthesis of a soluble oligomeric PHEMA precursor containing polymerizable
      functions as side substituents. As the second step, the precursor is dissolved in
      equal amounts of 2-hydroxyethyl methacrylate (HEMA) and water, to form a viscous
      but still injectable syrup. A low temperature water soluble initiator is then
      added. The curing reaction starts promptly and is completed within few minutes.
      During the entire process the internal temperature never rises above 40 degrees
      C. Preliminary mechanical characterizations performed on the hydrogels in their
      water-swollen state and diffusion tests in absorption/desorption experiments
      clearly indicated that on all respects the novel hydrogels are comparable with
      conventional PHEMA hydrogels obtained according to literature from HEMA in the
      presence of divinyl crosslinkers. However, the much shorter curing time combined
      with the far lower curing temperature endow the new hydrogels with a higher
      potential in view of specific surgical requirements, and particularly for in situ
      preparation.

PMID- 15468254
TI  - Elastic properties of poly(hydroxybutyrate) molecules.
AB  - Elasticity of various poly(hydroxybutyrate) (PHB) molecules of regular and
      irregular conformational structure was examined by the molecular mechanics (MM)
      calculations. Force - distance functions and the Young's moduli E were computed
      by stretching of PHB molecules. Unwinding of the 2(1) helical conformation H is
      characterized at small deformations by the Young's modulus E = 1.8 GPa. The H
      form is transformed on stretching into the highly extended twisted form E,
      similar to the beta-structure observed earlier by X-ray fiber diffraction. The
      computations revealed that in contrast to paraffins, the planar all-trans
      structure of undeformed PHB is bent. Hence, a PHB molecule attains the maximum
      contour length in highly straightened, but slightly twisted conformations. A
      dependence of the single-chain moduli of regular and disordered conformations on
      the chain extension ratio x was found. The computed data were used to analyze
      elastic response of tie (bridging) molecules in the interlamellar (IL) region of
      a semi-crystalline PHB. A modification of the chain length distribution function
      of tie molecules tau(N) due to secondary crystallization of PHB was conjectured.
      The resulting narrow distribution tau(N) comprises the taut tie molecules of
      higher chain moduli prone to overstressing. The molecular model outlined is in
      line with the macroscopically observed increase in the modulus and brittleness of
      PHB with storage time.

PMID- 15468255
TI  - Interactions of enzymes and a lectin with a chitin-based graft copolymer having
      polysarcosine side chains.
AB  - The molecular-recognition abilities of a water-soluble chitin derivative, chitin
      graft-polysarcosine (2) were investigated using chitinase, lysozyme, and wheat
      germ agglutinin (WGA). The enzymatic degradabilities of 2 were evaluated using
      chitinase and lysozyme. The molecular weight of those compounds of 2 with a
      higher affinity toward water decreased rapidly, as compared with partially
      deacetylated chitin (1). The 1H NMR spectrum of the low-molecular-weight
      fraction, yielded after lysozymic hydrolysis, indicated that saccharide residues
      in the chitinous backbone were specifically recognized by the lysozyme, then beta
      glycosidic linkages in the backbone were selectively hydrolyzed. Furthermore, the
      molecular-recognition ability of the chitinous backbone of graft copolymer 2
      toward the lectin WGA was elucidated by the enzyme-linked lectin-binding assay
      (ELLA). It was revealed that the graft copolymer with a lower degree of
      substitution (DS) value efficiently interacted with WGA. Interestingly, a graft
      copolymer having longer polysarcosine side chains showed higher recognition
      ability toward WGA than that having short side chains.

PMID- 15468256
TI  - Modulation of proteins adsorption onto the surface of chitosan complexed with
      anionic copolymers. Real time analysis by surface plasmon resonance.
AB  - The interpolyelectrolyte complex formation between chitosan and anionic
      polyacrylic derivatives, bearing sulfonic moieties, as well as the protein
      adsorption onto the chitosan/polyacrylic complexes were studied by surface
      plasmon resonance (SPR) optical biosensor. This unique technique allows a real
      time monitoring of different surface molecular interactions with very high
      sensitivity. The acrylic macromolecules are two families of copolymers of 2
      acrylamido-2-methylpropane sulfonic acid (AMPS) and, respectively, 2
      hydroxyethylmethacrylate (HEMA) and N,N'-dimethylacrylamide (DMAA). The
      complexation process was evaluated through the SPR measurements resulting from
      the flowing of polyacrylic aqueous solution over the sensor previously coated
      with chitosan. The SPR was able to differentiate strong ionic bonds from other
      weak and reversible interactions. By means of the coated sensors (uncomplexed and
      the whole series of complexed chitosan), SPR cold be used for a simple "in vitro"
      protein adsorption analysis, by flowing aqueous solutions of albumin and
      fibrinogen. While both proteins were adsorbed on the uncomplexed chitosan, the
      complexed coatings exhibited different and very promising behaviors. In
      particular, they showed no adsorption or only selective adsorption of albumin.

PMID- 15468257
TI  - Hydrogel networks of poly(ethylene oxide) star-molecules supported by expanded
      polytetrafluoroethylene membranes: characterization, biocompatibility evaluation
      and glucose diffusion characteristics.
AB  - The present work discusses the grafting by electron beam irradiation of
      poly(ethylene oxide) (PEO) star-shaped polymers onto porous expanded
      polytetrafluoroethylene (EXPTFE) surfaces. The resulting materials are intended
      to combine the good biocompatible properties of PEO with the outstanding
      mechanical properties of PTFE. The star-shaped PEOs were synthesized via anionic
      polymerization. 3 Mev electron beam irradiation was applied to graft these PEO
      stars onto porous EXPTFE surfaces. The hydrophobic EXPTFE surface had to be pre
      modified with N-vinylpyrrolidone. ESCA was used to quantify the amount of grafted
      star-shaped PEO. Unmodified EXPTFE surfaces are well known, when implanted in a
      body, to be rapidly covered by a layer of cells and fibrin. The EXPTFE coated
      with PEO were implanted in the peritoneal cavity of rats (or under the back
      skin). This implantation did not induce any inflammation reactions and SEM
      analysis had attested the absence of adsorbed cells and fibrin. The glucose
      diffusion properties of these membranes were studied by a lag time analysis
      method and compared to those of pure PEO hydrogels. As expected, glucose diffuses
      through the hydrogel coated membrane and diffusion is not affected by the
      presence of the EXPTFE membrane.

PMID- 15468258
TI  - Synthesis and characterization of polymeric linseed oil grafted methyl
      methacrylate or styrene.
AB  - Syntheses of wholly natural polymeric linseed oil (PLO) containing peroxide
      groups have been reported. Peroxidation, epoxidation and/or perepoxidation
      reactions of linseed oil, either under air or under oxygen flow at room
      temperature, resulted in polymeric peroxides, PLO-air and PLO-ofl, containing 1.3
      and 3.5 wt.-% of peroxide, with molecular weights of 2 100 and 3 780 Da,
      respectively. PLO-air contained cross-linked film up to 46.1 wt.-% after a
      reaction time of 60 d, associated with a waxy, soluble part (PLO-air-s) that was
      isolated with chloroform extraction. PLO-ofl was obtained as a waxy, viscous
      liquid without any cross-linked part at the end of 24 d under visible irradiation
      and oxygen flow. Polymeric peroxides, PLO-air-s and PLO-ofl initiated the free
      radical polymerization of both methyl methacrylate (MMA) and styrene (S) to give
      PMMA-graft-PLO and PS-graft-PLO graft copolymers in high yields with Mw varying
      from 37 to 470 kDa. The polymers obtained were characterized by FT-IR, (1)H NMR,
      TGA, DSC and GPC techniques. Cross-linked polymers were also studied by means of
      swelling measurements. PMMA-graft-PLO graft copolymer film samples were also used
      in cell-culture studies. Fibroblast cells were well adhered and proliferated on
      the copolymer film surfaces, which is important in tissue engineering.

PMID- 15468259
TI  - Micro construction of poly(epsilon-caprolactone)/poly(L-lactic acid) blend film
      by solution casting under microwave irradiation.
AB  - The micro construction of poly(epsilon-caprolactone) (PCL) and poly(L-lactic
      acid) (PLLA) blend films fabricated by solution casting under microwave
      irradiation was investigated by selective enzymatic degradation and scanning
      electron microscopy (SEM). The results were totally different from the blends
      obtained by conventional methods. The blend was more homogeneous and the PCL
      continuous phase more compact as no spherulites and tiny zone separation were
      observed from the film surface and no PCL network was observed inside the film,
      and the degradation of a PCL plank by Pseudomonas lipase was significantly
      retarded. The distributed PLLA micro spheres were enlarged and amorphous. The
      thermal behavior of the blend by microwave heating revealed that PCL and PLLA
      underwent a melting process, which induced the variations of the PCL phase and
      PLLA spheres. The weight loss caused by degradation of the PCL/PLLA blend
      obtained by conventional methods (B50c) is greater than that of the blend
      obtained by microwave methods (B50m), which reflects the change in morphology
      from a loose PCL network (B50c) to a dense PCL plank (B50m).

PMID- 15468260
TI  - Novel photopolymerizable biodegradable triblock polymers for tissue engineering
      scaffolds: synthesis and characterization.
AB  - For use in micro-patterned scaffolds in tissue engineering, novel diacrylated
      triblock macromers (PLA-b-PCL-b-PLA, PGA-b-PCL-b-PGA and PCL-b-PEO-b-PCL) were
      synthesized and characterized by Fourier transform infrared spectroscopy (FTIR),
      nuclear magnetic resonance spectroscopy (NMR) and gel permeation chromatography
      (GPC). All diacrylated polymers were designed as triblock copolymers and involved
      biodegradable blocks of relatively non-polar epsilon-caprolactone (CL) and polar
      monomers such as glycolide (GA), lactide (LA) or ethylene oxide (EO). All
      triblock polymers were prepared in molecular weights of a few kilo daltons via
      the anionic ring-opening polymerization (ROP) of the corresponding lactide,
      glycolide or caprolactone using stannous octoate [Sn(Oct)(2)] as catalyst. The
      polymers had low polydispersity indices, ranging from 1.23 to 1.56. Biodegradable
      polymeric networks were prepared with conversions of 72-84% via
      photopolymerization of the triblock diacrylated polymers with 2,2-dimethoxy-2
      phenylacetophenone (DMPA) as photoinitiator. PLA-b-PCL-b-PLA copolymers crumbled
      easily and were not suitable for micro-patterning. PGA-b-PCL-b-PGA copolymers had
      higher water contact angles than PCL-b-PEO-b-PCL and were also cytocompatible
      with Fibroblasts 3T3.

PMID- 15468261
TI  - Concanavalin a immobilized affinity adsorbents for reversible use in yeast
      invertase adsorption.
AB  - Concanavalin A (Con A) immobilized poly(2-hydroxyethyl methacrylate) (PHEMA)
      beads were investigated for specific adsorption of yeast invertase from aqueous
      solutions. PHEMA beads were prepared by a suspension polymerization technique
      with an average size of 150-200 microm, and activated by epichlorohydrin. Con A
      was then immobilized by covalent binding onto these beads. The maximum Con A
      immobilization was found to be 10 mg/g. The invertase-loading capability of the
      PHEMA/Con A beads was 107 mg/g. The maximum invertase adsorption capacity on the
      PHEMA/Con A adsorbents was observed at pH 5.0. The values of the Michaelis
      constant K(m) of invertase were significantly larger upon adsorption, indicating
      decreased affinity by the enzyme for its substrate, whereas V(max) was smaller
      for the adsorbed invertase. Adsorption improved the pH stability of the enzyme as
      well as its temperature stability. Thermal stability was found to increase with
      adsorption. The adsorbed enzyme activity was found to be quite stable in repeated
      experiments. Storage stability of adsorbed invertase.

PMID- 15468262
TI  - Design of temperature sensitive imprinted polymer hydrogels based on multiple
      point hydrogen bonding.
AB  - Weakly cross-linked temperature sensitive imprinted polymer hydrogels that
      recognize L-pyroglutamic acid (Pga) molecules via multiple-point hydrogen bonding
      were designed and synthesized. The amount of adsorption for Pga in imprinted
      hydrogels is 3-4 times higher than that in non-imprinted hydrogels. The
      selectivity test of imprinted polymer gels was carried out by using a series of
      structurally related compounds Pga, pyrrolidine, 2-pyrrolidone, L-proline as
      substrates. The results show that imprinted polymer gels exhibit high selectivity
      for Pga as compared to all the other tested substrates. The imprinted polymer
      hydrogels show good temperature sensitivity, special selectivity and reusability,
      suggesting that the polymer hydrogels would have an enormous potential for
      application in controlled drug release and separation field.

PMID- 15468263
TI  - Fully-biodegradable poly(3-hydroxybutyrate)/poly(vinyl alcohol) blend films with
      compositional gradient.
AB  - Fully-biodegradable bacterial poly(3-hydroxybutyrate) (PHB)/chemosynthetic
      poly(vinyl alcohol) (PVA) blend films with compositional gradient from one
      surface to the other surface of the films were prepared by a dissolution
      diffusion technique. Three kinds of PVA samples, high- and low-molecular weight
      atactic PVA and highly syndiotactic PVA (s-PVA), were used in order to
      investigate the effects of molecular weight and tactic structure on the
      generation of compositional gradient. The solution of PHB in 1,1,1,3,3,3
      hexafluoro-2-propanol (HFIP), which is also a good solvent for PVA, was cast on
      the PVA film and then the solvent HFIP was evaporated. By selecting the optimum
      volume of solvent and the evaporation rate, the PHB/PVA blend film with
      compositional gradient was obtained. The formation of compositional gradient was
      confirmed by FT-IR microscopy and ATR-FT-IR analysis. The 50%/50% PHB/s-PVA blend
      film with a nearly ideal compositional gradient, that is, the composition of PHB
      (or PVA) in the film changing gradually from 100% at one surface to 0% at the
      other surface of the film was obtained by casting PHB/HFIP solution on to the s
      PVA film. Positional dependence of the absorbance of C==O and OH stretching bands
      along the film thickness direction for the PHB/S-PVA cast films.

PMID- 15468264
TI  - End-functionalised 1-vinyl-2-pyrrolidinone oligomers bearing lactate functions at
      one end.
AB  - 1-Vinyl-2-pyrrolidinone (VP) oligomers bearing a lactate group at one end (PVP-L)
      were obtained by chain-transfer controlled radical polymerisation carried out in
      the presence of ethyl L-lactate as chain-transfer agent (CTA). Their number
      average molecular weights were in the range 1500-4000 with molecular weight
      distributions ranging from 1.4 to 1.8. The chain transfer constant, C(T), of the
      ethyl L-lactate/VP system was determined by monitoring the variation of PVP-L
      number-average molecular weight on conversion. The C(T) value so obtained was
      1.03 x 10(-2), which is by about one order of magnitude higher than the C(T)
      value previously determined for a seemingly similar system, namely methyl
      isobutyrate/1-vinyl-2-pyrrolidinone (1.64 x 10(-3)). The resultant PVP-L
      oligomers were thoroughly characterised by means of (1)H and (13)C NMR, in order
      to ascertain the regular presence of the lactate functions at one of their chain
      terminals. NMR characterisations gave results in full agreement with the proposed
      structure. Moreover, the molecular weight values determined by NMR very closely
      agreed with those obtained by SEC. Preliminary biological evaluations of the PVP
      L oligomers showed a complete lack of toxicity.

PMID- 15468265
TI  - Local chain mobility of gellan in aqueous systems studied by fluorescence
      depolarization.
AB  - The local chain mobility of a gellan, an electrolyte polysaccharide, in aqueous
      systems was examined with respect to the effect of the temperature, the
      concentration of gellan (c(G)), and the concentration of added salt (c(S)). The
      relaxation time of local motion was estimated for fluorescein isothiocyanate
      (FITC)-labeled-gellan by the fluorescence depolarization technique, and the chain
      mobility was discussed. The relaxation time increased with decreasing
      temperature, in particular when accompanying the coil-helix transition due to the
      great difference in chain mobility between the coil and the helical
      conformations. The effect of c(G) was observed for gellan solutions even below
      the critical concentration of chain entanglement (2 wt.-%) for well-expanded
      nonelectrolyte polymers with size similar to that of the gellan. This suggests
      that the actual excluded volume of gellan is larger than that of nonelectrolyte
      polymers due to the electrostatic repulsion between segments. The relaxation time
      for 0.2 wt.-% systems of gellan in coil conformation is independent of c(S),
      whereas a c(S) dependence of the relaxation time is clearly observed for 0.5 wt.
      % systems. The degree of expansion of the gellan chain is independent of the
      shielding effect of cations on the electrostatic repulsion between gellan
      segments due to the stiffness of gellan chain. On the other hand, the c(G) as
      well as the c(S) dependence of the chain mobility is clearly observed for gellan
      in the helical conformation, examined over the concentration range, probably due
      to the partial aggregation of helices induced by the attractive interaction
      between gellan segments.

PMID- 15468266
TI  - Enzymatic synthesis and chemical recycling of poly(carbonate-urethane).
AB  - Novel enzymatically recyclable poly(carbonate-urethane) consisting of a
      diurethane moiety as a hard segment and a carbonate linkage as an enzymatically
      cleavable unit was prepared by the polycondensation of biodegradable
      diurethanediol and diethyl carbonate using lipase. The produced poly(carbonate
      urethane) was readily transformed by lipase into the corresponding cyclic
      oligomers which were more easily repolymerized by lipase to produce a higher
      molecular weight poly(carbonate-urethane) than that of the parent poly(carbonate
      urethane).

PMID- 15468267
TI  - Release of chlorambucil from poly(N-isopropylacrylamide) hydrogels with beta
      cyclodextrin moieties.
AB  - The present work is focused on investigating the behavior of controlled drug
      release poly(N-isopropylacrylamide) (PNIPA) hydrogels in the presence of beta
      cyclodextrin (beta-CD). For this purpose, three types of NIPA hydrogels with beta
      CD moieties were synthesized with different architectures according to our
      previous studies. An anti-cancer drug (chlorambucil, CLB), which can form an
      inclusion complex with beta-CD, was selected for loading and in vitro release
      studies. The drug was loaded into hydrogels via a swelling method. DSC was used
      to study the interactions between the CLB molecules and the polymers. The results
      indicate that the CLB-polymer interactions are at the molecular level. Loading
      CLB into these polymers can result in an evident decrease in the glass transition
      temperature (T(g)), and the variation of T(g) (DeltaT(g)) depends on the
      structures of the polymers and their beta-CD content. The controlled release
      experiments show that the presence of beta-CD can markedly enhance CLB release
      from shrunken PNIPA hydrogels and increase the ratio of CLB released in total
      drug loading content. Release profile of CLB from hydrogels 1a-c and 4 at pH 1.4
      and 7.4, at 37 degrees C.

PMID- 15468268
TI  - Tissue engineering: key elements and some trends.

PMID- 15468269
TI  - Bone tissue engineering: state of the art and future trends.
AB  - Although several major progresses have been introduced in the field of bone
      regenerative medicine during the years, current therapies, such as bone grafts,
      still have many limitations. Moreover, and in spite of the fact that material
      science technology has resulted in clear improvements in the field of bone
      substitution medicine, no adequate bone substitute has been developed and hence
      large bone defects/injuries still represent a major challenge for orthopaedic and
      reconstructive surgeons. It is in this context that TE has been emerging as a
      valid approach to the current therapies for bone regeneration/substitution. In
      contrast to classic biomaterial approach, TE is based on the understanding of
      tissue formation and regeneration, and aims to induce new functional tissues,
      rather than just to implant new spare parts. The present review pretends to give
      an exhaustive overview on all components needed for making bone tissue
      engineering a successful therapy. It begins by giving the reader a brief
      background on bone biology, followed by an exhaustive description of all the
      relevant components on bone TE, going from materials to scaffolds and from cells
      to tissue engineering strategies, that will lead to "engineered" bone. Scaffolds
      processed by using a methodology based on extrusion with blowing agents.

PMID- 15468270
TI  - Extracellular matrix-like surfactant polymers containing arginine-glycine
      aspartic acid (RGD) peptides.
AB  - We report on a novel series of biomimetic polymers exhibiting interfacial
      properties similar to the extracellular matrix. A series of well-defined
      surfactant polymers were synthesized by simultaneously incorporating arginine
      glycine-aspartic acid (RGD) peptide, dextran oligosaccharide, and hexyl ligands
      with controlled feed ratios onto a poly(vinyl amine) (PVAm) backbone. The peptide
      sequence was H-GSSSGRGDSPA-NH(2) (Pep) having a hydrophilic extender at the amino
      terminus and capped carboxy terminus. The peptide-to-dextran (Pep:Dex) ratios
      were varied to create surfactants having 0, 25, 50, 75, and 100 mol-% peptide
      relative to dextran. The surfactants were characterized by IR, NMR and atomic
      force microscopy (AFM) for composition and surface active properties. AFM
      confirmed full surface coverage of PVAm(Pep)(100%) on graphite, and supported the
      mechanism of interdigitation of hexyl ligands between surfactant molecules within
      a specified range of hexyl chain densities. the attachment and growth of human
      pulmonary artery endothelial cells on the PVAm(Pep)(100%) surface was identical
      to the fibronectin positive control. Cell adhesion decreased dramatically with
      decreasing peptide density on the surfactant polymers. Molecular model of a
      peptide surfactant polymer, consisting of poly(vinyl amine) backbone with
      peptide, dextran oligosaccharide and hexyl branches coupled to the polymer chain.

PMID- 15468271
TI  - Fibers and 3D mesh scaffolds from biodegradable starch-based blends: production
      and characterization.
AB  - The aim of this work is the production of fibers from biodegradable polymers to
      obtain 3D scaffolds for tissue engineering of hard tissues. The scaffolds
      required for this highly demanding application need to have, as well as the
      biological and mechanical characteristics, a high degree of porosity with
      suitable dimensions for cell seeding and proliferation. Furthermore, the open
      cell porosity should have adequate interconnectivity for a continuous flow of
      nutrients and outflow of cell metabolic residues as well as to allow cell growth
      into confluent layers. Blends of corn starch, a natural biodegradable polymer,
      with other synthetic polymers (poly(ethylene vinyl alcohol), poly(epsilon
      caprolactone), poly(lactic acid)) were selected for this work because of their
      good balance of properties, namely biocompatibility, processability and
      mechanical properties. Melt spinning was used to produce fibers from all the
      blends and 3D meshes from one of the starch-poly(lactic acid) blends. The
      experimental characterization included the evaluation of the tensile mechanical
      properties and thermal properties of the fibers and the compression stiffness,
      porosity and degradation behavior of the 3D meshes. Light microscopy picture of
      3D meshes.

PMID- 15468272
TI  - Polypyrrole thin films formed by admicellar polymerization support the osteogenic
      differentiation of mesenchymal stem cells.
AB  - The objective of this study was to evaluate the attachment, proliferation, and
      differentiation of rat mesenchymal stem cells (MSC) toward the osteoblastic
      phenotype seeded on polypyrrole (PPy) thin films made by admicellar
      polymerization. Three different concentrations of pyrrole (Py) monomer (20, 35,
      and 50 x 10(-3) M) were used with the PPy films deposited on tissue culture
      polystyrene dishes (TCP). Regular TCP dishes and PPy polymerized on TCP by
      chemical polymerization without surfactant using 5 x 10(-3) M Py, were used as
      controls. Rat MSC were seeded on these surfaces and cultured for up to 20 d in
      osteogenic media. Surface topography was characterized by atomic force
      microscopy, X-ray photoelectron spectroscopy, and static contact angle. Cell
      attachment, proliferation, alkaline phosphatase (ALP) activity, and calcium
      content were measured to evaluate the ability of MSC to adhere and differentiate
      on PPy-coated TCP. Increased monomer concentrations resulted in PPy films of
      increased thickness and surface roughness. PPy films generated by different
      monomer concentrations induced drastically different cellular events. A wide
      spectrum of cell attachment characteristics (from excellent cell attachment to
      the complete inability to adhere) were obtained by varying the monomer
      concentration from 20 m to 50 x 10(-3) M. In particular the 20 x 10(-3) M PPy
      thin films demonstrated superior induction of MSC osteogenicity, which was
      comparable to standard TCP dishes, unlike PPy films of similar thickness prepared
      by chemical polymerization without surfactant. Adhesion of mesenchymal stem cells
      on tissue culture plates (TCP) coated with polypyrrole thin films made by
      admicellar polymerization.

PMID- 15468273
TI  - Controlled delivery achieved with bi-layer matrix devices produced by co
      injection moulding.
AB  - The aim of this study was to design new soy protein-based bi-layered co-injection
      moulded matrix systems aimed to achieve controlled drug delivery. The devices
      consisted of a drug-free outer layer (skin) and a drug-containing core. The
      systems overcame the inherent disadvantage of non-linear release associated with
      diffusion-controlled single-layer matrix devices by providing additional
      releasing area with time to compensate for the decreasing release rate. As
      expected, the bi-layer devices presented a significant decrease in drug release
      rate when compared with a correspondent single layer matrix system. The skin
      thickness and the degree of crosslinking of the core appeared to be very
      important tools to tailor the release patterns. Furthermore, due to the
      amphoteric nature of the soy protein, the developed devices evidenced a pH
      dependent behaviour. The mechanisms of drug release were also elucidated at two
      different pH values: i) pH 5.0, near the isoelectric point of soy (low matrix
      solubility); and ii) pH 7.4, physiological pH (high matrix solubility).
      Consequently, changing the release medium from pH 5.0 to pH 7.4 after two hours,
      led to an abrupt increase in drug release and the devices presented a typical
      controlled drug delivery profile: slow release/fast release. These evidences may
      provide for the development of individual systems with different release onsets
      that in combination may exhibit drug releases at predetermined times in a pre
      programmed way. Another possibility is the production of three-layer devices
      presenting bimodal release profiles (fast release/slow release/fast release) by
      similar technologies. Scanning electron micrograph of a developed bi-layer
      device.

PMID- 15468274
TI  - Thermally produced biodegradable scaffolds for cartilage tissue engineering.
AB  - A novel process was developed to fabricate biodegradable polymer scaffolds for
      tissue engineering applications, without using organic solvents. Solvent residues
      in scaffolds fabricated by processes involving organic solvents may damage cells
      transplanted onto the scaffolds or tissue near the transplantation site. Poly(L
      lactic acid) (PLLA) powder and NaCl particles in a mold were compressed and
      subsequently heated at 180 degrees C (near the PLLA melting temperature) for 3
      min. The heat treatment caused the polymer particles to fuse and form a
      continuous matrix containing entrapped NaCl particles. After dissolving the NaCl
      salts, which served as a porogen, porous biodegradable PLLA scaffolds were
      formed. The scaffold porosity and pore size were controlled by adjusting the
      NaCl/PLLA weight ratio and the NaCl particle size. The characteristics of the
      scaffolds were compared to those of scaffolds fabricated using a conventional
      solvent casting/particulate leaching (SC/PL) process, in terms of pore structure,
      pore-size distribution, and mechanical properties. A scanning electron
      microscopic examination showed highly interconnected and open pore structures in
      the scaffolds fabricated using the thermal process, whereas the SC/PL process
      yielded scaffolds with less interconnected and closed pore structures. Mercury
      intrusion porosimetry revealed that the thermally produced scaffolds had a much
      more uniform distribution of pore sizes than the SC/PL process. The utility of
      the thermally produced scaffolds was demonstrated by engineering cartilaginous
      tissues in vivo. In summary, the thermal process developed in this study yields
      tissue-engineering scaffolds with more favorable characteristics, with respect
      to, freedom from organic solvents, pore structure, and size distribution than the
      SC/PL process. Moreover, the thermal process could also be used to fabricate
      scaffolds from polymers that are insoluble in organic solvents, such as
      poly(glycolic acid). Cartilage tissue regenerated from thermally produced PLLA
      scaffold.

PMID- 15468275
TI  - Production and characterization of chitosan fibers and 3-D fiber mesh scaffolds
      for tissue engineering applications.
AB  - This study reports on the production of chitosan fibers and 3-D fiber meshes for
      the use as tissue engineering scaffolds. Both structures were produced by means
      of a wet spinning technique. Maximum strain at break and tensile strength of the
      developed fibers were found to be 8.5% and 204.9 MPa, respectively. After 14 d of
      immersion in simulated body fluid (SBF), scanning electron microscopy (SEM),
      energy dispersive spectroscopy (EDS), and inductively coupled plasma emission
      (ICP) spectroscopy analyses showed that a bioactive Ca-P layer was formed on the
      surface of the fibers, meaning that they exhibit a bioactive behavior. The
      samples showed around 120% max. swelling in physiological conditions. The pore
      sizes of 3-D chitosan fiber mesh scaffolds were observed to be in the range of
      100-500 microm by SEM. The equilibrium-swelling ratio of the developed scaffolds
      was found to be around 170% (w/w) in NaCl solution at 37 degrees C. Besides that,
      the limit swelling strain was less than 30%, as obtained by mechanical
      spectroscopy measurements in the same conditions. The viscoelastic properties of
      the scaffolds were also evaluated by both creep and dynamic mechanical tests. By
      means of using short-term MEM extraction test, both types of structures (fibers
      and scaffolds) were found to be non-cytotoxic to fibroblasts. Furthermore,
      osteoblasts directly cultured over chitosan fiber mesh scaffolds presented good
      morphology and no inhibition of cell proliferation could be observed.Osteoblast
      like cells proliferating over chitosan based fibers after 7 d of culture.

PMID- 15468276
TI  - Determination of the three-dimensional, solution-phase structure of the macrolide
      antibiotic oxolide in CD2Cl2 and D2O from NMR constraints.
AB  - The three-dimensional structure of the antibiotic oxolide, (9S,11S)-11-amino-9
      deoxo-11,12-deoxy-9,12-epoxyerythromycin, was determined in CD2Cl2 through
      constrained molecular mechanics with constraints derived from proton NMR. The
      calculations yielded a well-defined global minimum. Data acquired for oxolide in
      D2O, although not as complete, indicate that the antibiotic adopts the same
      conformation in water.

PMID- 15468277
TI  - A complete 1H and 13C NMR data assignment for four drimane sesquiterpenoids
      isolated from Drimys winterii.
AB  - From the bark of Drimys winterii Forst., the drimane derivatives drimendiol,
      polygodial, isotadeonal and isodrimeninol were isolated. Complete and unambiguous
      1H and 13C NMR chemical shift assignments of these compounds were achieved by
      COSY experiments, 13C/1H shift correlation diagrams and NOE experiments.
      Isotadeonal and isodrimeninol were found for the first time in this plant
      species.

PMID- 15468278
TI  - The reporting quality of abstracts of randomised controlled trials submitted to
      the ICS meeting in Heidelberg.
AB  - AIMS: The quality of randomised controlled trials (RCTs) is associated with bias.
      Thus, reports of RCTs must have enough detail of key elements of quality to
      enable them to be interpreted properly. This study examines the quality of
      abstracts of RCTs reported at the ICS meeting in Heidelberg in 2002, using the
      CONSORT statement as the gold standard. MATERIALS AND METHODS: All of the
      abstracts accepted for the meeting at Heidelberg were read to identify reports of
      RCTs. Copies of these were printed and examined to see whether they complied with
      the 22 items in the CONSORT statement. As these were all abstracts the first
      CONSORT item was changed so that to comply the title had to say it was a
      randomised trial. Each item was scored as not met, partially met, met. RESULTS:
      Fifty-three reports of RCTs were found. Five of these were podium presentations,
      14 discussion posters, and 34 non-discussion posters. Most reports did not comply
      with many of the items in the CONSORT statement, lacking particularly in
      technical details of the methods (only one study clearly reported hidden
      allocation to groups), and how the results were presented (only two studies fully
      reported results). Only 2/53 of the abstracts complied fully with more than 10 of
      the items, and 30/53 did not comply at all with 10 or more. CONCLUSIONS: The
      quality of reporting of studies at ICS is so poor that it is difficult to
      interpret the results. Reporting was particularly poor on the details of the
      randomisation and the numeric results.

PMID- 15468279
TI  - Correlation of non-invasive urodynamics with International Prostate Symptom Score
      (IPSS) and prostate volume.
AB  - AIM: To study the correlation between non-invasive urodynamic data, the
      International Prostate Symptom Score (IPSS) and the prostate volume. MATERIALS
      AND METHODS: Data of 667 healthy volunteers participating in a longitudinal study
      of changes in urinary bladder contractility secondary to BPE were analyzed. The
      prostate volume was assessed by transabdominal ultrasonography. Uroflowmetry
      followed to verify if a minimum free flow rate of 4.5 ml/sec could be achieved.
      While (re)filling the bladder by drinking, the subjects completed the Dutch
      version of the IPSS. Next, the bladder pressure was non-invasively measured using
      the condom catheter method. The urethral resistance (URR) was calculated from the
      maximum condom pressure and the maximum free flow rate. RESULTS: The IPSS ranged
      from 0 to 29, (6.1 +/- 4.8) (mean +/- SD), whereas the prostate volumes ranged
      from 8 to 140 cm3, (34 +/- 18). Twenty eight percent (185/667) of the subjects
      had a non-invasively quantified high URR and a significantly higher IPSS (7.3 +/-
      5.2) than those with a low URR (IPSS (5.7 +/- 4.6)), Mann-Whitney U-test: P <
      0.001. The IPSS and the URR were significantly correlated, Spearman's rho (rho) =
      0.20, P < 0.001. A significant difference between the prostate volumes, 36 +/- 21
      cm3 in the high URR versus 33 +/- 17 cm3 in the low URR group, was not found, P =
      0.18. CONCLUSIONS: A weak though statistically significant correlation was found
      between the non-invasively quantified URR and the IPSS. This suggests that an
      elevated resistance is a necessary, but not a sufficient condition for lower
      urinary tract symptoms (LUTS). No correlation was found between the URR and the
      prostate volume.

PMID- 15468281
TI  - High activity of enzymes immobilized in colloidal nanoreactors.
AB  - We present a novel type of nanoreactor suitable for the immobilization of
      enzymes. The particles used consist of a polystyrene core onto which long chains
      of poly(acrylic acid) are grafted ("spherical polyelectrolyte brush"). Proteins
      adsorbed spontaneously onto these particles from aqueous solutions if the ionic
      strength is low. We immobilized glucoamylase on these particles and showed that
      this enzyme keeps nearly its full activity. This is shown by analyzing the
      enzymatic activity in terms of the Michaelis-Menten kinetics. No leaching out of
      the enzyme takes place during the reaction and the colloidal stability is not
      impeded by the adsorbed biomolecules. The data presented here suggest that the
      principle of immobilizing enzymes on these particles may be of general use.The
      Figure shows a schematic representation of the colloidal nanoreactors.

PMID- 15468282
TI  - Fabrication of honeycomb-patterned cellulose films.
AB  - This paper reports for the first time on the fabrication of honeycomb-patterned
      cellulose films by casting water in oil emulsion of cellulose acetate onto a
      glass substrate and subsequent deacetylation treatment. The honeycomb pore size
      could be controlled from 1 to 100 microm under a saturated water vapor condition.
      Both cellulose and cellulose acetate films with honeycomb-pattern are expected to
      be a two-dimensional model of plant cell walls as well as of micro-wells for
      single cell cultivation. Surface topographic image of a honeycomb-patterned
      cellulose film (scalebar: 50 microm).

PMID- 15468283
TI  - Spherical molecularly imprinted polymers (SMIPs) via a novel precipitation
      polymerization in the controlled delivery of sulfasalazine.
AB  - Spherical molecularly imprinted polymers (SMIPs) have been prepared via a novel
      precipitation polymerization using sulfasalazine (prodrug used in the diseases of
      the colon) as template. The sulfasalazine was incorporated into SMIPs and into a
      spherical non-imprinted polymer (control), and then the release rate of the
      bioactive agent at different pH values was evaluated. Considerable differences in
      the release characteristics between imprinted and non-imprinted polymers have
      been observed. This opens the possibility of the development of drug release
      systems capable of modulating the release of a specific molecule.
      Photomicrography of spherical molecularly imprinted polymers (SMIPs).

PMID- 15468284
TI  - Effect of drug-loading methods on drug load, encapsulation efficiency and release
      properties of alginate/poly-L-arginine/chitosan ternary complex microcapsules.
AB  - The drug-loaded alginate/poly-L-arginine/chitosan ternary complex microcapsules
      were prepared by mixing method, absorption method and the combined method of
      mixing and absorption, respectively. The effect of drug-loading methods on drug
      load, the encapsulation efficiency and the release properties of the complex
      microcapsules were investigated. The results showed that the absorption process
      is a dominating factor to greatly increase the drug load of Hb into
      microcapsules. Upon loading Hb into microcapsules by combined method of mixing
      and absorption, the drug load (19.9%) is up to the maximum value, and the
      encapsulation efficiency is 93.8%. Moreover, the drug release is a zero-order
      kinetics process for the ternary complex microcapsules made by mixing. For the
      complex microcapsules made by absorption, the drug release is a first-order
      kinetics. However, for the complex microcapsules made by combining the mixing and
      the absorption, the drug release obeys a first-order kinetics during the first
      eighteen hours, changing afterwards to a zero-order kinetics process. Effect of
      drug-loading methods on drug load and encapsulation efficiency of alginate/poly-L
      arginine/chitosan ternary complex microcapsules.

PMID- 15468285
TI  - Acrylonitrile-acrylic acid copolymer membrane imprinted with uric acid for
      clinical uses.
AB  - The preparation of new polymeric membranes using molecular imprinting technology
      for application in blood filtration devices is described. Membranes, based on an
      acrylic acid-acrylonitrile copolymer, produced through phase inversion, were
      modified by introducing specific binding sites for uric acid into their
      structure. The materials prepared are intended for use to selectively remove uric
      acid from the blood in the case of increased serum uric acid values associated
      with different pathologies. The interactions at a molecular level between the
      membrane forming copolymer and the template were investigated by means of
      calorimetry, infrared spectroscopy and morphological analysis. The presence of
      interactions between the template and the copolymer, and a good thermal stability
      of the imprinted membranes were observed. In addition, the results of rebinding
      tests on the imprinted membranes indicated a good capacity of molecular
      recognition for the template and satisfactory selectivity properties towards
      compounds of similar structure such as theophylline. Membrane permeability values
      suggest their application as (ultra) haemofiltration devices. Poly(acrylonitrile
      co-acrylic acid) membrane.

PMID- 15468286
TI  - Association of calcium phosphate and fibroblast growth factor-2: a dynamic light
      scattering study.
AB  - The size distributions of fibroblast growth factor-2 (FGF-2) in aqueous solutions
      with neutral pH were investigated with a dynamic light scattering technique. We
      found that the FGF-2 was distributed in dimer or trimer form at concentrations of
      0.1-1.0 mg . mL(-1). An aggregate with a hydrodynamic radius of approximately 90
      nm coexisted with this and its proportion increased with a decrease in
      concentration. At lower concentrations (less than 0.10 mg . mL(-1)) FGF-2
      aggregates with an average radius of 80-100 nm were dominant and were stable for
      more than a day. These FGF-2 solutions were mixed with calcium phosphate
      solutions to produce a sub-micron sized compound of FGF-2 and hydroxyapatite,
      which could be used as a biological implant that possessed a pharmacological
      function for bone formation. By utilizing a transformation from amorphous calcium
      phosphate to hydroxyapatite, FGF-2 was effectively incorporated into polycrystals
      of hydroxyapatite.SEM photograph of a mixture of hydroxyapatite and FGF-2.

PMID- 15468287
TI  - Preparation and characterization of biodegradable microspheres containing
      hepatitis B surface antigen.
AB  - Poly-DL-lactide-poly(ethylene glycol) (PELA) microspheres containing Hepatitis B
      surface antigen (HBsAg) were elaborated by a solvent extraction method based on
      the formation of a double water/oil/water (w/o/w) emulsion. Microspheres were
      characterized in terms of morphology, size and size distribution, encapsulation
      efficiency, and the efficiency of microsphere formation (EMF). Transmission
      electron microscopy (TEM) and polyacrylamide gel electrophoresis (PAGE) were used
      to investigate the structural integrality of HBsAg encapsulated in PELA
      microspheres. The release profile was investigated by the measurement of antigen
      present in the release medium at various intervals. The PELA-10 microspheres
      displayed the highest antigen encapsulation efficiency (about 80%), and antigen
      molecules could be stabilized in the PELA-10 microspheres during the preparation
      process. It suggested that the PELA microspheres had a great potential as a new
      polymer adjuvant for HBsAg. The release of Hepatitis B surface antigen from poly
      DL-lactide-poly(ethylene glycol) microspheres.

PMID- 15468289
TI  - Differential expression of proteins in rat plasma exposed to benzene.
AB  - Benzene, a ubiquitous environmental contaminant, is an important solvent in the
      chemical industry and is also known as a constituent of petroleum. It has been
      reported that benzene is associated with hematotoxicity including leukemia in
      humans and cancer in laboratory animals. To study protein expression alterations
      in rat plasma exposed to benzene, rats were exposed to levels of 1, 10, 100 ppm
      benzine for 6 h/day and 5 d/week for 2 or 6 weeks. Two-dimensional gel
      electrophoresis of rat plasma was carried out, and approximately 1000 protein
      spots were detected on the gels. The 11 spots which showed significantly
      different expression were selected and identified with matrix-assisted laser
      desorption/ionization-time of flight-mass spectrometry. Analyzing the targeted 11
      spots, there was no correlation between the 2 and 6 weeks benzene-inhaled groups
      on up-regulated proteins (zinc finger protein, and tristetraprolin) and on down
      regulated proteins (cAMP-regulated guanine nucleotide exchange factor II, protein
      kinase and unknown protein). The overexpressed proteins (inhibitor of kappaB-like
      protein, GTP-binding protein rab14, T-cell receptor alpha chain, and somatostatin
      transactivating factor-1) were detected only in groups inhaling benzene for 6
      weeks. Among them the expression level of T-cell receptor alpha chain was
      confirmed by Western blot.

PMID- 15468290
TI  - Towards a proteomic analysis of atopic dermatitis: a two-dimensional
      polyacrylamide gel electrophoresis/mass spectrometric analysis of cultured
      patient-derived fibroblasts.
AB  - Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease typically
      characterized by a distribution of eczematous skin lesions with lichenification,
      pruritic excoriations, and dry skin with wide varieties of pathophysiologic
      aspects. Recently, AD was divided into extrinsic and intrinsic forms according to
      the presence or absence of an allergy. We investigated alterations in protein
      expression in primary cultured AD cells from the patient biopsy samples by two
      dimensional gel electrophoresis (2-DE) and matrix-assisted laser
      desorption/ionization-time of flight. In the primary cultured fibroblasts, we
      obtained 31 candidate proteins from the two-dimensional gel image analysis in
      which 18 proteins were up-regulated, eight proteins were down-regulated and five
      proteins were post-translationally modified. From these 2-DE results, we found
      several candidate genes matched proteomic expression patterns by semiquantitative
      reverse transcription PCR. Since the exact mechanism of atopic alterations in
      fibroblasts remains unknown, our results may provide new clues to aid in
      understanding AD.

PMID- 15468291
TI  - Significance of pad test loss for the evaluation of women with urinary
      incontinence.
AB  - AIMS: The aim of this study was to determine whether the objective incontinence
      severity, as measured by the pad test, correlated with urethral parameters, and
      if the objective incontinence severity was differentiated by the incontinence
      types and also, if it influenced the patient's clinical outcome. METHODS: Two
      hundred seventy-four female patients who had undergone a tension-free vaginal
      tape procedure between March 1999 and May 2003 were retrospectively reviewed. The
      1 hr pad test was carried out as recommended by the International Continence
      Society, with some modification. The mean patient age was 55.1 years (range: 28
      80). Two hundred-one women (73.3%) that complained of stress urinary incontinence
      and another 73 women (26.7%) that had additional symptoms of urge incontinence
      were enrolled as study subjects. A cure for incontinence, after the tension-free
      vaginal tape procedure, was defined as the absence of a subjective complaint of
      leakage and the absence of objective leakage on stress testing, and all other
      cases were considered failures. RESULTS: In linear regression analysis, the
      Valsalva leak point pressure (VLPP) was the only explanatory variable influencing
      the objective incontinence severity. The urine leakage was significant higher in
      the mixed urinary incontinence group than in the stress urinary incontinence
      group (39.7 +/- 7.5 g vs. 30.3 +/- 2.8 g, P < 0.05). For the total patients, the
      failure group had a more severe preoperative objective severity than the cure
      group (53.2 +/- 16.6 vs. 32.0 +/- 3.0, P < 0.05). Upon a subgroup analysis, a
      similar result was found in the stress urinary incontinence group (87.1 +/- 8.2
      vs. 29.8 +/- 2.8, P < 0.05) but not in the mixed urinary incontinence group.
      CONCLUSIONS: Our findings suggest that the amount of urine leakage as measured
      during the pad test may be associated with the clinical outcome, after the anti
      incontinence surgery.

PMID- 15468292
TI  - Mammary ECM composition and function are altered by reproductive state.
AB  - To address whether reproductive state alters mammary gland extracellular matrix
      (ECM) composition and function, ECM was isolated from nulliparous, pregnant,
      lactating, involuting, and regressed rat mammary glands. The ECM composition of
      fibronectin, tenascin, laminin, clusterin, and MMPs was found to vary
      dramatically with reproductive state. In 3-dimensional (3-D) culture, we
      identified novel effects of these endogenous mammary matrices on mammary
      epithelial cells. Specifically we found that (1) matrix isolated from nulliparous
      animals promoted the formation of epithelial ducts with bifurcation, (2) matrix
      isolated from mid-involuting mammary glands induced cell death, (3) matrix
      isolated from late-stage involuting glands restored glandular development, while
      (4) matrix isolated from parous animals restricted glandular morphogenesis. Our
      data were consistent with mammary gland ECM facilitating epithelial cell
      proliferation, differentiation, death, and glandular reorganization that occur
      during the pregnancy and involution cycle. Further, we show that the parous gland
      has persistent changes in ECM function. Cumulatively, our data demonstrated that
      the microenvironment of the normal adult mammary gland is highly plastic, which
      has important implications for mammary tumor cell progression and dormancy. These
      data also raised the possibility of targeting mammary matrix production with
      preventive or therapeutic interventions.

PMID- 15468293
TI  - Coregulators and chromatin remodeling in transcriptional control.
AB  - Despite many years of investigation by numerous investigators, transcriptional
      regulatory control remains an intensely investigated and continuously evolving
      field of research. Transcriptional regulation is dependent not only on
      transcription factor activation and chromatin remodeling, but also on a host of
      transcription factor coregulators-coactivators and corepressors. In addition to
      transcription factor activation and chromatin changes, there is an expanding
      array of additional modifications that titrate transcriptional regulation for the
      specific conditions of a particular cell type, organ system, and developmental
      stage, and such events are likely to be greatly influenced by upstream signaling
      cascades. Here, we will briefly review the highlights and perspectives of
      chromatin remodeling and transcription controls as affected by cofactor
      availability, cellular energy state, relative ratios of reducing equivalents, and
      upstream signaling. We also present the C-terminal binding protein (CtBP) as a
      novel nuclear receptor (NR) coregulator, which exemplifies the integration of a
      number of transcriptional regulatory controls.

PMID- 15468294
TI  - An overview of polylactides as packaging materials.
AB  - Polylactide polymers have gained enormous attention as a replacement for
      conventional synthetic packaging materials in the last decade. By being truly
      biodegradable, derived from renewable resources and by providing consumers with
      extra end-use benefits such as avoiding paying the "green tax" in Germany or
      meeting environmental regulations in Japan, polylactides (PLAs) are a growing
      alternative as a packaging material for demanding markets. The aim of this paper
      is to review the production techniques for PLAs, summarize the main properties of
      PLA and to delineate the main advantages and disadvantages of PLA as a polymeric
      packaging material. PLA films have better ultraviolet light barrier properties
      than low density polyethylene (LDPE), but they are slightly worse than those of
      cellophane, polystyrene (PS) and poly(ethylene terephthalate) (PET). PLA films
      have mechanical properties comparable to those of PET and better than those of
      PS. PLA also has lower melting and glass transition temperatures than PET and PS.
      The glass transition temperature of PLA changes with time. Humidity between 10
      and 95% and storage temperatures of 5 to 40 degrees C do not have an effect on
      the transition temperature of PLA, which can be explained by its low water
      sorption values (i.e. <100 ppm at Aw = 1). PLA seals well at temperatures below
      the melting temperature but an appreciable shrinking of the films has been noted
      when the material is sealed near its melting temperature. Solubility parameter
      predictions indicate that PLA will interact with nitrogen compounds, anhydrides
      and some alcohols and that it will not interact with aromatic hydrocarbons,
      ketones, esters, sulfur compounds or water. The CO2, O2 and water permeability
      coefficients of PLA are lower than those of PS and higher than those of PET. Its
      barrier to ethyl acetate and D-limonene is comparable to PET. The amount of
      lactic acid and its derivatives that migrate to food simulant solutions from PLA
      is much lower than any of the current average dietary lactic acid intake values
      allowed by several governmental agencies. Thus, PLA is safe for use in
      fabricating articles for contact with food.

PMID- 15468295
TI  - Macromolecular dimensions and mechanical properties of monolayer films of
      Sonorean mesquite gum.
AB  - Mesquite gum sourced from Prosopis velutina trees and gum arabic (Acacia spp.)
      were characterized using light scattering and Langmuir isotherms. Both gum
      materials were fractionated by hydrophobic interaction chromatography, yielding
      four fractions for both gums: FI, FIIa, FIIb and FIII in mesquite gum and FI,
      FII, FIIIa and FIIIb in gum arabic. In mesquite gum, the obtained fractions had
      different protein content (7.18-38.60 wt.-%) and macromolecular dimensions (M
      approximately 3.89 x 10(5)-8.06 x 10(5) g.mol(-1), RG approximately 48.83-71.11
      nm, RH approximately 9.61-24.06 nm) and architecture given by the structure
      factor (RG/RH ratio approximately 2.96-5.27). The mechanical properties of
      Langmuir monolayers at the air-water interface were very different on each gum
      and their fractions. For mesquite gum, the most active species at the interface
      were those comprised in Fractions IIa and IIb and III, while Fraction I the pi/A
      isotherm lied below that of the whole gum. In gum arabic only Fraction III
      developed greater surface pressure at the same surface per milligram of material
      than whole gum. This is rationalized in terms of structural differences in both
      materials. Mesquite gum tertiary structure seems to fit best with an elongated
      polydisperse macrocoil in agreement with the "twisted hairy rope" proposal for
      arabinogalactan proteoglycans.

PMID- 15468296
TI  - A new method for the evaluation of biodegradable plastic using coated cellulose
      paper.
AB  - A highly sensitive analytical method for evaluation of poly(L-lactide) (PLA),
      poly(epsilon-caprolactone) (PCL), poly(beta-hydroxybutyrate) (PHB), and
      poly(butylene succinate) (PBS) degradability was developed using coated cellulose
      paper, prepared by penetration and adhesion of these plastics into/onto the
      cellulose paper. Enzymatic degradability of the obtained plastic coated papers
      was evaluated using various commercial proteases and lipases. PLA coated paper
      was highly susceptible to subtilisin and mammalian enzymes, alpha-chymotrypsin,
      elastase and trypsin. To our knowledge, this is the first report on the
      degradation of PLA coated paper using subtilisin and mammalian enzymes. Almost
      all lipase preparations degraded PCL and PHB coated papers but not PBS coated
      paper. The biodegradability of plastic coated paper was greater than that of
      plastic powder. The penetration of plastic into cellulose paper by coating
      improved the plastic degradability, and can be regulated easily.

PMID- 15468297
TI  - Porous-conductive chitosan scaffolds for tissue engineering, 1. Preparation and
      characterization.
AB  - Novel porous-conductive chitosan scaffolds were fabricated by incorporating
      conductive polypyrrole (PPy) particles into a chitosan matrix and employing a
      phase separation technique to build pores inside the scaffolds. Conductive
      polypyrrole particles were prepared with a microemulsion method using FeCl3 as a
      dopant. The preparation conditions were optimized to obtain scaffolds with
      controlled pore size and porosity. The conductivity of the scaffolds was
      investigated using a standard four-point probe technique. It was found that
      several kinds of scaffolds showed a conductivity close to 10(-3) S.cm(-1) with a
      low polypyrrole loading of around 2 wt.-%. The main mechanical properties, such
      as tensile strength, breaking elongation and Young's modulus of the scaffolds,
      were examined both in the dry and in the hydrated states. The results indicated
      that a few different kinds of scaffolds exhibited the desired mechanical strength
      for some tissue engineering applications. The miscibility of polypyrrole and
      chitosan was also evaluated using a dynamic mechanical method. The presence of
      significant phase separation was detected in non-porous PPy/chitosan scaffolds
      but enhanced miscibility in porous PPy/chitosan scaffolds was observed.

PMID- 15468298
TI  - Cell attachment and proliferation on poly(carbonate urethanes) with various
      degrees of nanophase separation.
AB  - In this work, we synthesized six 4,4'-diphenylmethane diisocyanate (MDI)-based
      poly(carbonate urethanes) (PCU) by using the macrodiol poly(1,6-hexyl, 1,2-ethyl
      carbonate) diol (MW = 2,017) in different molar ratios to MDI. The bulk and
      surface properties of cast PCU films were analyzed. The glass transition
      temperatures measured by dynamic mechanical analysis (DMA) and surface images
      obtained from atomic force microscopy (AFM) indicated that these PCU had various
      degrees of nanophase separation that changed with the time and film casting
      temperatures. The degree of nanophase separation correlated very well with
      endothelial cell attachment and proliferation on PCU.

PMID- 15468299
TI  - Formation and degradation of poly(D,L-lactide) nanoparticles and their potential
      application as controllable releasing devices.
AB  - In the presence of surfactant, water-insoluble poly(D,L-lactide) (PLA) was
      dispersed into narrowly distributed nanoparticles stable in water via microphase
      inversion. The structure and degradation of such formed nanoparticles were
      investigated by a combination of static and dynamic laser light scattering. Our
      results revealed that the degradation rate increased with the temperature and pH
      so that the degradation could be regulated from minutes to days. Using anionic
      sodium dodecyl sulfate (SDS) as stabilizer resulted in a slower degradation than
      using cationic hexadecyltrimethylammonium bromide (HTAB). The phthalocyanine
      chromophores (PC) could be encapsulated inside these PLA nanoparticles. The
      degradation of individual PLA nanoparticles led to a controllable releasing of
      PC. The absorption and fluorescence studies revealed a correlation between the
      degradation and the releasing of PC. Our results showed that a higher PC/PLA
      ratio could lead to a faster degradation.

PMID- 15468300
TI  - Identification of caspase-3 degradome by two-dimensional gel electrophoresis and
      matrix-assisted laser desorption/ionization-time of flight analysis.
AB  - The activation of caspases is a critical event for the execution phase of
      programmed cell death. Caspases are highly specific in their ability to activate
      or inhibit many crucial proteins in the cell via site-specific cleavage. To date,
      more than 60 proteins have been shown to be substrates of one or more caspases in
      mammalian cells, and the list is still growing. In this study, to identify human
      caspase-3 substrates, we digested lysates obtained from a caspase-3-deficient MCF
      7 cell line with purified caspase-3 and analyzed eliminated or decreased spots by
      2-DE. Proteins degraded by caspase-3, termed as caspase-3 degradome, are involved
      in a variety of cellular functions, such as stress-responsive proteins, signaling
      molecules, structural proteins, and unclassified proteins. Interestingly, the
      cellular level of vinculin, a caspase-3 substrate, was dramatically reduced
      during the apoptotic process, where the expression level of caspase-3 was
      increased. This degradomic approach could provide a powerful tool in finding
      physiological substrates of many proteolytic enzymes whose functions remain to be
      determined.

PMID- 15468301
TI  - Neurofibromatosis type 1 and hereditary non-polyposis colorectal cancer: is there
      a link?

PMID- 15468302
TI  - Reversal of the transformed phenotype and inhibition of peptidylglycine alpha
      monooxygenase in Ras-transformed cells by 4-phenyl-3-butenoic acid.
AB  - Recent studies have shown that the proliferation of some tumor cells is dependent
      on autocrine growth loops that require amidated autocrine growth factors.
      Peptidylglycine alpha-monooxygenase (PAM) is required for amidation of these
      growth factors and, therefore, this enzyme is an attractive target for anti-tumor
      compounds. 4-Phenyl-3-butenoic acid (PBA) is an irreversible turnover-dependent
      inhibitor of PAM in vitro and has been shown to decrease lung cancer cell
      proliferation by inhibiting the synthesis of amidated growth factors. We show
      here that PBA (0.1 mg/mL) inhibits the growth of Ras-transformed epithelial cells
      (WB-Ras) but has little effect on the proliferation of normal epithelial cells
      (WB-Neo). The methyl ester derivative of PBA (PBA-Me) at 10-fold lower
      concentration also exhibits a selective inhibition of Ras-transformed cell growth
      compared to normal epithelial cell growth. In addition, PBA produces a
      significant upregulation of gap junctional communication between WB-Ras cells
      following 2-5 day treatments, with a corresponding increase in the degree of
      connexin 43 phosphorylation and an increase in the number of connexin 43
      containing plasma membrane gap junction plaques. Western blot analyses indicate
      no effect of PBA on the proportion of p21 Ras in the membrane versus cytosolic
      fractions or on p44/42 MAP kinase phosphorylation. Furthermore, the cell
      morphology of PBA-treated WB-Ras cells is altered, so as to more closely resemble
      that of non-transformed WB-Neo cells. PAM activity was assayed in both WB-Ras and
      WB-Neo cells, and we demonstrate that PBA at long treatment times (4 days)
      inhibits PAM activity in both cell types at concentrations that produce selective
      growth inhibition of WB-Ras cells. Shorter PBA treatment times (24 h), however,
      inhibit PAM activity in WB-Ras but not WB-Neo cells, an effect that was mimicked
      by PBA-Me. Taken together, these results clearly demonstrate that PBA returns Ras
      transformed cells to a more normal phenotype, a finding consistent with the known
      increased dominance of the Ras signaling pathway in transformed epithelial cells.

PMID- 15468303
TI  - Structures of new secofriedelane and friedelane acids from Calophyllum inophyllum
      of French Polynesia.
AB  - Three new friedelane-type triterpenoids, 3,4-secofriedelan-3,28-dioic acid (1),
      27-hydroxyacetate canophyllic acid (2) and 3-oxo-27-hydroxyacetate friedelan-28
      oic acid (3), were isolated from the leaves of Calophyllum inophyllum
      (Clusiaceae) grown in French Polynesia. Their structures were established by the
      concerted application of 2D NMR techniques including gs-COSY, gs-HMQC and gs
      HMBC.

PMID- 15468304
TI  - Myositis complicating viridans streptococcal sepsis in childhood leukemia.
AB  - Hematogenous focal infections are a rare complication of bacteremia or sepsis
      caused by viridans-group streptococci. We describe two patients with acute
      leukemia who developed myositis during alpha-hemolytic streptococcal bacteremia.
      Children complaining of severe muscle pain associated with viridans streptococcal
      infections should be carefully evaluated for the presence of focal pyogenic
      complications and rhabdomyolysis. The severity of infectious myositis is highly
      variable, depending on the etiologic organism and host immunity, making
      individualized treatment the most effective approach.

PMID- 15468305
TI  - Epstein-Barr virus-associated peripheral T-cell lymphoma and hemophagocytic
      syndrome arising after liver transplantation: case report and review of the
      literature.
AB  - Post-transplantation lymphoproliferative disorders (PTLD) are a well-recognized
      complication of solid organ transplantation. The vast majority of PTLD are
      Epstein-Barr virus (EBV)-related infections that manifest as B-cell malignancies.
      We report an unusual case of an EBV-associated T-cell lymphoma in a 10-year-old
      boy who had previously undergone liver transplantation at age 4 years. He
      presented with hemophagocytic syndrome (HPS) and active EBV infection, with
      positive serum titers and polymerase chain reaction (PCR) for EBV in blood,
      colon, and antral samples.

PMID- 15468306
TI  - Phosphorylation of Artemis following irradiation-induced DNA damage.
AB  - Artemis is a DNA repair factor required for V(D)J recombination, repair of DNA
      damage induced by ionizing radiation (IR) or radiomimetic drugs, and the
      maintenance of genome integrity. During V(D)J recombination, Artemis participates
      in the resolution of hairpin-sealed coding ends, a step crucial to the
      constitution of the gene encoding for the antigen receptor of lymphocytes. The
      precise role of Artemis in the repair of IR-induced DNA damage remains to be
      elucidated. Here we show that Artemis is constitutively phosphorylated in
      cultured cells and undergoes additional phosphorylation events after irradiation.
      The IR-induced phosphorylation is mainly, although not solely, dependent on
      Ataxia-telangiectasia-mutated kinase (ATM). The physiological role of these
      phosphorylation events remains unknown, as in vitro-generated Artemis mutants,
      which present impaired IR-induced phosphorylation, still display an activity
      sufficient to complement the V(D)J recombination defect and the increased
      radiosensibility of Artemis-deficient cells. Thus, Artemis is an effector of DNA
      repair that can be phosphorylated by ATM, and possibly by DNA-PKcs and ATR
      depending upon the type of DNA damage.

PMID- 15468307
TI  - High-risk surgically resected pediatric melanoma and adjuvant interferon therapy.
AB  - BACKGROUND: Pediatric patients with high-risk surgically resected melanoma are at
      risk for relapse, yet little is known about these young patients and how they
      tolerate high-dose interferon therapy. PROCEDURE: We reviewed medical records of
      patients (< or =18 years) with high-risk melanoma referred to the University of
      Michigan Pediatric Hematology-Oncology service between January 1989 and July
      2003. RESULTS: Fourteen patients were identified with high-risk resected
      melanoma. The median age at diagnosis was 8.5 years. The median time to establish
      diagnosis was 9 months. Primary lesions were diagnosed as unequivocal melanoma,
      atypical epithelioid melanocytic proliferations, or atypical Spitz tumor with
      indeterminate malignant potential. Twelve patients had a positive sentinel lymph
      node (SLN) biopsy or a palpable regional lymph node and underwent regional lymph
      node dissection (LND). Two patients with unequivocal melanoma with Breslow depth
      >4 mm had negative SLN biopsies. Twelve patients received adjuvant high-dose
      interferon. The following toxicities were observed: constitutional symptoms,
      gastrointestinal symptoms, depression or neuropsychiatric symptoms,
      myelosuppression, elevated AST or ALT, hypothyroidism, and hypertension. Grade 3
      or 4 toxicities were uncommon with exception of neutropenia, resulting in
      modification of therapy in one patient. All patients are alive and free of
      disease at follow-up (median 24.5 months). CONCLUSIONS: Invasive melanoma can
      occur in very young children. Despite early signs of malignancy, there is often a
      delay in diagnosis. Histologically, diagnosis may be difficult because of overlap
      with Spitz nevi. Pediatric patients tolerated adjuvant high-dose interferon well
      and may be less likely than adults to require therapy modification secondary to
      toxicities.

PMID- 15468308
TI  - Thrombocytosis and toxocariasis: report of two pediatric cases.
AB  - We report two cases of visceral larva migrans (VLM) syndrome by Toxocara in
      children. The biological presentation was unusual and characterized by persistent
      secondary thrombocytosis (>1,000 x 10(9)/L) mimicking an essential
      thrombocythemia and variable hypereosinophilia syndrome. Both children had non
      specific symptoms including abdominal pain, skin rash, and fever. The diagnosis
      was confirmed by serology. The children were treated with either thiabendazole or
      albendazole, resulting in normalization of eosinophil and platelet counts.

PMID- 15468309
TI  - Soluble p185(HER-2) in patients with malignant bone tumours.
AB  - BACKGROUND: This study was initiated to test the hypothesis that soluble p185(HER
      2) could be of value as a diagnostic or predictive marker for patients with
      malignant bone tumours. PROCEDURE: Sera of 35 patients with high-grade malignant
      osteosarcoma (n = 27) and Ewing Sarcoma (n = 8) were tested at the time of
      diagnosis by ELISA and compared with sera of controls (n = 38) and clinical data.
      RESULTS: In patients with osteosarcoma and Ewing Sarcoma, levels of sp185(HER-2)
      did not differ significantly from levels in controls. These results were
      irrespective of the type of tumour, survival chemotherapy or other clinical
      variables. CONCLUSION: p185(HER-2) serum levels do not appear to be of diagnostic
      or predictive value for differentiation of high-grade osteosarcoma and Ewing
      Sarcoma.

PMID- 15468310
TI  - Molecular characterization of a novel splice site mutation within the CYBB gene
      leading to X-linked chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a primary immunodeficiency that affects
      the oxidative mechanism of microbial killing of phagocytic cells. The defect is
      characterized by a lack or severely reduced superoxide anion (O2-) production by
      phagocytes. Seventy percent of CGD cases are X-linked (X-CGD) and they are caused
      by mutations in the gene encoding for gp91(phox), one of the two subunits of the
      flavocytochrome b558 of the NADPH oxidase. We identified an abnormal transcript
      arising from a novel splice site mutation within the gene encoding gp91(phox),
      which suggested that the mutation affected normal mRNA splicing. Thus, the effect
      of this mutation leads to the complete absence of the flavocytochrome b558 in
      neutrophil membranes, which caused the biochemical phenotype X91 degrees-CGD in
      this family. These molecular findings help to explain the early onset and severe
      phenotype in this X-CGD kindred.

PMID- 15468311
TI  - Protein biomarkers in the plasma of workers occupationally exposed to polycyclic
      aromatic hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons (PAHs) form a chemical family containing several
      hundred compounds, including benzo[a]pyrene and pyrene. They are usually produced
      by the incomplete burning of coal, oil, gas, garbage, or other organic substances
      like tobacco or charbroiled meat. Exposure to PAH causes tumors, primarily in the
      lung, the bladder, and the skin. To investigate the differentially expressed
      proteins resultant from PAH exposure, the protein expression in human plasma was
      analyzed using two-dimensional electrophoresis (2-DE). The plasma exposed to PAH
      was obtained from 48 waste gas pollution measurers working at an automobile
      emission inspection center. The 1-hydroxypryene (1-OHP) level, which is the
      urinary PAH metabolite used for evaluation of PAH exposure, was 0.28 micromol/mol
      creatinine in PAH exposure groups, and 0.078 micromol/mol creatinine in unexposed
      groups (control, n = 33). A protein upregulated by PAH (putative capacitative
      calcium entry channel) and five overexpressed proteins (two fibrinogen gamma-A
      chain precursors, a hemopexin precursor, an albumin precursor, and T-cell
      receptor beta chain C region) were identified with matrix assisted laser
      desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and
      confirmed with tandem MS (MS/MS) and Western blotting. The putative capacitative
      calcium entry channel was partially validated with a laboratory made antibody of
      a representative peptide fragment in PAH-exposed human plasma samples.

PMID- 15468312
TI  - Loss of myostatin expression alters fiber-type distribution and expression of
      myosin heavy chain isoforms in slow- and fast-type skeletal muscle.
AB  - Myostatin (Mstn) is a member of the transforming growth factor-beta family that
      negatively regulates skeletal muscle mass. Mstn knockout mice have greater
      skeletal muscle mass than wild-type littermates. We investigated the effect of
      Mstn on fiber type by comparing adult muscles from the murine Mstn knockout with
      wild-type controls. Based on myofibrillar ATPase staining, the soleus of Mstn
      knockout mice displays a larger proportion of fast type II fibers and a reduced
      proportion of slow type I fibers compared with wild-type animals. Based on
      staining for succinate dehydrogenase (SDH) activity, a larger proportion of
      glycolytic fibers and a reduced proportion of oxidative fibers occur in the
      extensor digitorum longus (EDL) of Mstn knockouts. These differences in
      distribution of fiber types are accompanied by differences in the expression of
      myosin heavy chain (MHC) isoforms. In both Mstn knockout soleus and EDL, larger
      numbers of faster MHC isoforms are expressed at the expense of slower isoforms
      when compared with wild-type littermates. Thus, the absence of Mstn in the
      knockout mouse leads to an overall faster and more glycolytic muscle phenotype.
      This muscle phenotype is likely a consequence of developmental processes, and
      inhibition of Mstn in adults does not cause a transformation to a more fast and
      glycolytic phenotype. Our findings suggest that myostatin has a critical role in
      regulating the formation, proliferation, or differentiation of fetal myoblasts
      and postnatal fibers.

PMID- 15468313
TI  - X-linked Charcot-Marie-Tooth disease: phenotypic expression of a novel mutation
      Ile127Ser in the GJB1 (connexin 32) gene.
AB  - We report a family with X-linked dominant Charcot-Marie-Tooth disease (CMTX1).
      Three affected family members are described, who underwent detailed clinical,
      electrophysiological, molecular genetic, and histopathological studies. A novel
      isoleucine at position 127 with serine (Ile127Ser) mutation in the gap junction
      protein beta 1 (GJB1) gene was detected. The electrophysiological findings were
      consistent with a primary demyelinating neuropathy with secondary axonal loss and
      support this model of disease progression. All patients having the CMT phenotype
      and intermediate conduction velocities who are negative for CMT1A
      duplication/hereditary neuropathy with liability to pressure palsies (HNPP)
      deletion, and whose family shows a dominant trait without male-to-male
      transmission, should be screened for CMTX1.

PMID- 15468314
TI  - Functional assessment of A delta and C fibers in patients with Fabry's disease.
AB  - The pathophysiology of neuropathic pain in Fabry's disease (FD) is still largely
      unknown. Seven FD patients were studied by laser evoked potentials (LEPs) to
      assess the function of the A delta and C fibers. Laser pulses were delivered on
      the skin of the hand and perioral region at painful intensity to record LEPs
      related to A delta-fiber inputs and at nonpainful intensity to obtain LEPs
      related to C-fiber inputs. When the perioral region was stimulated, a vertex
      positive component was recorded with a mean latency of 260.3 ms and 376 ms after
      A delta- and C-fiber stimulation, respectively. The mean A delta-LEP amplitude
      was significantly lower in FD patients (N1/P1 mean values were 2.8 microV and 4.5
      microV after hand and face stimulation, respectively, compared to 4 microV and
      8.9 microV for controls; N2/P2 mean values were 8.2 microV and 11.1 microV after
      hand and face stimulation, respectively, and 16.7 microV and 22.3 microV in
      controls). Unlike the healthy subjects, 6 FD patients, suffering from neuropathic
      pain, showed a late positive potential related to C-fiber function (mean latency,
      377.1 ms) also after facial stimulation at painful intensity, suggesting a
      relative overflow of C-fiber input, which may be relevant in the pathophysiology
      of pain in this disease.

PMID- 15468315
TI  - Impairment and distress associated with symptoms of male-typed and female-typed
      DSM-IV Axis-I disorders.
AB  - Recent research has established a pattern of impairment and distress associated
      with the symptoms of DSM-IV Axis-II disorders such that personality disorders
      occurring more commonly among males are associated with more social and
      occupational impairment, but less personal distress, than personality disorders
      occurring more commonly among females. The current study examined whether a
      similar pattern exists for DSM-IV Axis-I disorders. Lay judges (N = 206) rated
      the social impairment, occupational impairment, and personal distress associated
      with the symptoms of six male-typed and six female-typed Axis-I disorders.
      Impairment and distress were associated with male-typed and female-typed Axis-I
      disorders in the same manner as personality disorders. Reasons for the emphasis
      of social and occupational impairment among male-typed disorders and distress
      among female-typed disorders are discussed.

PMID- 15468316
TI  - The Chinese version of the social problem-solving inventory: some initial results
      on reliability and validity.
AB  - The development of an instrument that measures social problem solving of Chinese
      adolescents is reported. The Social Problem-Solving Inventory Revised (SPSI-R)
      was translated to Chinese, and content validity, cultural relevance, and reading
      level of the translated measure were reviewed by panels of experts. The Chinese
      version of the scale (C-SPSI-R) was then administered to a sample of 352 junior
      secondary-school students. Exploratory factor analyses revealed a 5-factor
      structure that was largely consistent with the structure of the original English
      language SPSI-R. The C-SPSI-R and its subscales were found to be internally
      consistent and temporally stable over time. The scores of the subscales were also
      correlated with depression scores, a correlation that supported the convergent
      validity of the subscales. Adolescents with high and low Chinese Beck Depression
      Inventory scores had significant differences in four out of five subscales of the
      C-SPSI-R (except Rational Problem-Solving). On the whole, the results supported
      that the C-SPSI-R is a reliable and valid instrument in the assessment of social
      problem solving in Chinese adolescents.

PMID- 15468317
TI  - MSDsite: a database search and retrieval system for the analysis and viewing of
      bound ligands and active sites.
AB  - The three-dimensional environments of ligand binding sites have been derived from
      the parsing and loading of the PDB entries into a relational database. For each
      bound molecule the biological assembly of the quaternary structure has been used
      to determine all contact residues and a fast interactive search and retrieval
      system has been developed. Prosite pattern and short sequence search options are
      available together with a novel graphical query generator for inter-residue
      contacts. The database and its query interface are accessible from the Internet
      through a web server located at: http://www.ebi.ac.uk/msd-srv/msdsite.

PMID- 15468318
TI  - Structural genomics of Pyrococcus furiosus: X-ray crystallography reveals 3D
      domain swapping in rubrerythrin.

PMID- 15468319
TI  - X-ray structure of Arabidopsis At2g06050, 12-oxophytodienoate reductase isoform
      3.

PMID- 15468320
TI  - Specific DNA recognition by the Antp homeodomain: MD simulations of specific and
      nonspecific complexes.
AB  - Four molecular dynamics simulation trajectories of complexes between the wild
      type or a mutant Antennapedia homeodomain and 2 DNA sequences were generated in
      order to probe the mechanisms governing the specificity of DNA recognition. The
      starting point was published affinity measurements showing that a single protein
      mutation combined with a replacement of 2 base pairs yields a new high-affinity
      complex, whereas the other combinations, with changes on only 1 macromolecule,
      exhibited lower affinity. The simulations of the 4 complexes yielded fluctuating
      networks of interaction. On average, these networks differ significantly,
      explaining the switch of affinity caused by the alterations in the
      macromolecules. The network of mostly hydrogen-bonding interactions involving
      several water molecules, which was suggested both by X-ray and NMR structures of
      the wild-type homeodomain and its DNA operator sequence, could be reproduced in
      the trajectory. More interestingly, the high-affinity complex with alterations in
      both the protein and the DNA yielded again a dynamic but very tight network of
      intermolecular interactions, however, attributing a significantly stronger role
      to direct hydrophobic interactions at the expense of water bridges. The other 2
      homeodomain-DNA complexes, with only 1 molecule altered, show on average over the
      trajectories a clearly reduced number of protein-DNA interactions. The
      observations from these simulations suggest specific experiments and thus close
      the circle formed by biochemical, structural, and computational studies. The
      shift from a water-dominated to a more "dry" interface may prove important in the
      design of proteins binding DNA in a specific manner.

PMID- 15468321
TI  - Crystal structure of Bacillus subtilis YdaF protein: a putative ribosomal N
      acetyltransferase.

PMID- 15468322
TI  - Crystal structure of flavin binding to FAD synthetase of Thermotoga maritima.

PMID- 15468323
TI  - Effects of mutations in tyrosine hydroxylase associated with progressive dystonia
      on the activity and stability of the protein.
AB  - Tyrosine hydroxylase (TyrH) catalyzes the conversion of tyrosine to
      dihydroxyphenylalanine (DOPA), the rate-limiting step in the biosynthesis of
      dopamine. Four mutations in the TyrH gene have recently been described in cases
      of autosomal recessive DOPA-responsive dystonia (Swaans et al., Ann Hum Genet
      2000;64:25-31). All four are predicted to result in changes in single amino acid
      residues in the catalytic domain of the protein: T245P, T283M, R306H, and T463M.
      To determine the effects of these mutations on the molecular properties of the
      enzyme, mutant proteins containing the individual single amino acid changes have
      been expressed in bacteria and purified. Only the T283M mutation results in a
      decrease in the enzyme k(cat) value, while the T245P enzyme has a slightly higher
      value than the wild-type enzyme. The only case in which a K(m) value for either
      tyrosine or tetrahydrobiopterin is perturbed is the T245P enzyme, for which the
      K(m) value for tyrosine has increased about 50%. In contrast to the minor effects
      of the mutations on enzyme activity, the stability is decreased significantly by
      the mutations. The R306H and T283M enzymes are the least stable, losing activity
      30- and 50-fold more rapidly than the wild-type enzyme. The apparent T(m) value
      for unfolding was decreased by 3.9, 8.2, and 7.2 degrees for the T245P, R306H,
      and T463M enzymes, while the T283M enzyme was too unstable for measurement of a
      T(m) value. The results establish that the physiological effects of the mutations
      are primarily due to the decreased stability of the mutant proteins rather than
      decreases in their intrinsic activities.

PMID- 15468324
TI  - All-atom folding of the three-helix HIV accessory protein with an adaptive
      parallel tempering method.
AB  - All-atom protein structure prediction from the amino acid sequence alone remains
      an important goal of biophysical chemistry. Recent progress in force field
      development and validation suggests that the PFF01 free-energy force field
      correctly predicts the native conformation of various helical proteins as the
      global optimum of its free-energy surface. Reproducible protein structure
      prediction requires the availability of efficient optimization methods to locate
      the global minima of such complex potentials. Here we investigate an adapted
      version of the parallel tempering method as an efficient parallel stochastic
      optimization method for protein structure prediction. Using this approach we
      report the reproducible all-atom folding of the three-helix 40 amino acid HIV
      accessory protein from random conformations to within 2.4 A backbone RMS
      deviation from the experimental structure with modest computational resources.

PMID- 15468325
TI  - A search for consensus on the dimensional structure of personality disorders.
AB  - Previous attempts to elucidate the dimensional structure of personality disorders
      (PDs) have been based on single samples and measures. Like one-item tests, they
      are useful but scattered and potentially misleading glimpses at the true
      structure of PDs. Therefore, reanalyses of 33 previously published data sets were
      conducted using recommended statistical procedures to arrive at consensus
      structures. Similar reanalyses of published data were conducted on associations
      between PDs and the five-factor model of normal personality characteristics. High
      degrees of congruence were observed between the consensus PD structures and the
      consensus structures suggested by dimensions of normal personality. The analytic
      techniques used in the present study helped bypass methodological problems
      inherent in previous tests and revealed higher levels of support for both
      theoretically and empirically based representations of the five-factor model
      approach to PDs.

PMID- 15468326
TI  - MOLE: a data management application based on a protein production data model.
AB  - MOLE (mining, organizing, and logging experiments) has been developed to meet the
      growing data management and target tracking needs of molecular biologists and
      protein crystallographers. The prototype reported here will become a Laboratory
      Information Management System (LIMS) to help protein scientists manage the large
      amounts of laboratory data being generated due to the acceleration in proteome
      research and will furthermore facilitate collaborations between groups based at
      different sites. To achieve this, MOLE is based on the data model for protein
      production devised at the European Bioinformatics Institute (Pajon A, et al.,
      Proteins in press).

PMID- 15468327
TI  - Enumeration of antigen-specific CD8+ T lymphocytes by single-platform, HLA
      tetramer-based flow cytometry: a European multicenter evaluation.
AB  - BACKGROUND: HLA class I peptide tetramers represent powerful diagnostic tools for
      detection and monitoring of antigen-specific CD8(+) T cells. The impetus for the
      current multicenter study is the critical need to standardize tetramer flow
      cytometry if it is to be implemented as a routine diagnostic assay. Hence, the
      European Working Group on Clinical Cell Analysis set out to develop and evaluate
      a single-platform tetramer-based method that used cytomegalovirus (CMV) as the
      antigenic model. METHODS: Absolute numbers of CMV-specific CD8(+) T cells were
      obtained by combining the percentage of tetramer-binding cells with the absolute
      CD8(+) T-cell count. Six send-outs of stabilized blood from healthy individuals
      or CMV-carrying donors with CMV-specific CD8(+) T-cell counts of 3 to 10
      cells/microl were distributed to 7 to 16 clinical sites. These sites were
      requested to enumerate CD8(+) T cells and, in the case of CMV-positive donors,
      CMV-specific subsets on three separate occasions using the standard method.
      RESULTS: Between-site coefficients of variation of less than 10% (absolute CD8(+)
      T-cell counts) and approximately 30% (percentage and absolute numbers of CMV
      specific CD8(+) T cells) were achieved. Within-site coefficients of variation
      were approximately 5% (absolute CD8(+) T-cell counts), approximately 9%
      (percentage CMV-specific CD8(+) T cells), and approximately 17% (absolute CMV
      specific CD8(+) T-cell counts). The degree of variation tended to correlate
      inversely with the proportion of CMV-specific CD8(+) T-cell subsets. CONCLUSIONS:
      The single-platform MHC tetramer-based method for antigen-specific CD8(+) T-cell
      counting has been evaluated by a European group of laboratories and can be
      considered a reproducible assay for routine enumeration of antigen-specific
      CD8(+) T cells.

PMID- 15468328
TI  - In vitro-in vivo evaluation of supercritical processed solid dispersions:
      permeability and viability assessment in Caco-2 cells.
AB  - In this study improvement in the bioavailability of carbamazepine (CBZ) prepared
      as solid dispersions by conventional solvent evaporation and supercritical fluid
      (SCF) processing methods was assessed, along with the elucidation of the
      mechanism of improved absorption. Solid dispersions of CBZ in polyethylene glycol
      (PEG) with either Gelucire 44/14 or vitamin E-TPGS (TPGS) were evaluated by
      intrinsic dissolution. Directional transport through Caco-2 cell monolayers was
      determined in the presence and absence of TPGS. Cell viability in presence of
      various concentrations of amphiphilic carriers was seen. In vivo oral
      bioavailability was determined in rats. The apparent intrinsic dissolution rates
      (IDR) of both conventional- and SCF-CBZ/PEG 8000/TPGS solid dispersions were
      increased by 13- and 10.6-fold, respectively, relative to neat CBZ. CBZ was not a
      substrate of P-glycoprotein. Higher CBZ permeability was seen in presence of 0.1%
      TPGS. Cell viability studies showed significant cytotoxicity only at or above
      0.1% amphiphilic carrier. Supercritical treated formulation (without amphiphilic
      carrier) displayed oral bioavailability on par with those conventional solid
      dispersions augmented with amphiphilic carriers. An in vitro-in vivo correlation
      was seen between IDR and the AUC of the various CBZ solid dispersions.
      Bioavailability of CBZ was more a function of dissolution as opposed to membrane
      effects. Although bioavailability from SCF processed dispersions was better than
      conventionally processed counterparts (except for one formulation containing
      Gelucire 44/14), an interaction of processing method and inclusion of an
      amphiphilic carrier, rather by one factor alone contributed to optimal
      absorption, thus giving contradictory results for Gelucire 44/14 and TPGS
      formulations.

PMID- 15468329
TI  - FISH cytogenetics and prognosis in breast and non-small cell lung cancers.
AB  - BACKGROUND: Interphase cytogenetics by fluorescence in situ hybridization (FISH)
      has been demonstrated to be a valuable diagnostic tool in effusions from patients
      with solid tumors. As the next step, we investigated whether certain patterns of
      numeric aberrations in malignant effusion cells supply prognostic information.
      METHODS: From a large series of effusions from patients with solid tumors, 55
      effusions from breast cancer and 39 effusions from non-small cell lung cancer
      (NSCLC) were classified as malignant by cytology or FISH. Tumor cells were
      classified as FISH aneuploid for chromosome 11 and/or 17 or as not aneuploid.
      Predominant cytogenetic anomalies and patterns of intratumor cytogenetic
      heterogeneity were brought in relation to overall survival rate. RESULTS: There
      was no difference with respect to overall survival rate when effusions with or
      without aneuploidy for chromosomes 11 and 17 were compared. Likewise, in
      effusions with aneuploidy, there was no difference in overall survival rate among
      patients with different modal chromosome copy numbers (e.g., trisomy vs.
      tetrasomy 11) or among patients with a low or high grade of intratumor complexity
      (defined by the intratumor heterogeneity of FISH aneuploidy). In breast cancer,
      aneuploidy with gain of chromosome 11 was associated with a significantly
      superior survival rate, suggesting that amplification of chromosome 11 DNA is
      associated with a less aggressive phenotype. CONCLUSIONS: Simple chromosomal
      changes as determined by FISH, such as gain of chromosome 11 copy numbers in
      breast cancer, may be prognostic. Prospective studies in primary tumors that
      classify distinct prognostic groups by FISH cytogenetics are warranted.

PMID- 15468330
TI  - Characterization of site I of human serum albumin using spectroscopic analyses:
      locational relations between regions Ib and Ic of site I.
AB  - Site I of human serum albumin is an important and complex region for high
      affinity binding of drugs. Equilibrium dialysis showed independent binding of
      dansyl-L-asparagine (DNSA) and n-alkyl p-aminobenzoates (p-ABEs) to regions Ib
      and Ic, respectively, in the pH range 6.0-9.0. However, individual binding of
      DNSA increased with pH in the same range. Binding of the four n-alkyl p-ABEs
      strongly perturbed the circular dichroism spectrum of bound DNSA, and the effect
      increased with concentration and the number of carbon atoms in the alkyl moiety.
      A similar effect was observed by increasing pH from 6.0 to 9.0, a pH range in
      which human serum albumin is known to undergo the neutral-to-base transition. The
      spectral changes propose spatial orientation changes of DNSA at region Ib. This
      proposal was supported by increased fluorescence anisotropy values: n-alkyl p
      ABEs binding and the pH-dependent conformational change each restricted the
      mobility of the naphthalene ring of bound DNSA. Despite the similar effects on
      the spatial orientation of DNSA, clear differences were observed between the
      effects of n-alkyl p-ABEs and neutral-to-base transition. The former hardly
      changed the affinity and maximum fluorescence emission wavelength of bound DNSA;
      in contrast, the latter significantly affected them. The results give new
      information about site I and, according to our knowledge, represent a new type of
      ligand interaction, because the binding site of DNSA could be changed by
      simultaneous binding of the n-alkyl p-ABEs without affecting the binding
      constant.

PMID- 15468331
TI  - Role of DNA mismatch repair in apoptotic responses to therapeutic agents.
AB  - Deficiencies in DNA mismatch repair (MMR) have been found in both hereditary
      cancer (i.e., hereditary nonpolyposis colorectal cancer) and sporadic cancers of
      various tissues. In addition to its primary roles in the correction of DNA
      replication errors and suppression of recombination, research in the last 10
      years has shown that MMR is involved in many other processes, such as interaction
      with other DNA repair pathways, cell cycle checkpoint regulation, and apoptosis.
      Indeed, a cell's MMR status can influence its response to a wide variety of
      chemotherapeutic agents, such as temozolomide (and many other methylating
      agents), 6-thioguanine, cisplatin, ionizing radiation, etoposide, and 5
      fluorouracil. For this reason, identification of a tumor's MMR deficiency (as
      indicated by the presence of microsatellite instability) is being utilized more
      and more as a prognostic indicator in the clinic. Here, we describe the basic
      mechanisms of MMR and apoptosis and investigate the literature examining the
      influence of MMR status on the apoptotic response following treatment with
      various therapeutic agents. Furthermore, using isogenic MMR-deficient (HCT116)
      and MMR-proficient (HCT116 3-6) cells, we demonstrate that there is no enhanced
      apoptosis in MMR-proficient cells following treatment with 5-fluoro-2'
      deoxyuridine. In fact, apoptosis accounts for only a small portion of the induced
      cell death response.

PMID- 15468332
TI  - Soluble KDI domain of gamma1 laminin protects adult hippocampus from
      excitotoxicity of kainic acid.
AB  - Recent data indicate that the soluble KDI domain of gamma1 laminin promotes
      survival and neurite outgrowth of human central neurons in vitro (Liebkind et
      al.[2003] J Neurosci Res 73:637-643), and seems to neutralize both glia- and
      myelin-derived signals that hamper regeneration in the central nervous system
      (CNS) of adult mammals. We show that damage of adult rat neocortical and
      hippocampal areas by a stereotaxic injection of kainic acid (KA) is prevented by
      a preceding injection of the soluble KDI domain. In the presence of the KDI
      domain, both neocortical and hippocampal areas show extensive gliosis but have
      viable neurons and glial cells, which are absent and the areas fully destroyed
      after injection of KA alone. This result indicates that the KDI domain of the
      gamma1 laminin protects the CNS against excitotoxic insults and promotes survival
      of both neurons and glial cells. The KDI domain may thus be a potential drug to
      prevent CNS damage induced by neurodegenerative disorders, mechanical injury, or
      ischemia.

PMID- 15468333
TI  - Micropipette manipulation: a technique to evaluate the stability of water-in-oil
      emulsions containing proteins.
AB  - The interfacial properties and stability of water-in-oil emulsions containing
      protein were studied using micromanipulation. Micropipettes were used to produce
      individual water droplets in oil in a controlled manner on the micron scale. The
      pipettes were then used to bring two droplets into contact in order to observe
      fusion. The occurrence of fusion was investigated as a function of the
      compositions of both the continuous (oil) and dispersed (aqueous) phases. Various
      proteins, i.e., insulin, growth hormone, or serum albumin, were dissolved in the
      dispersed phase. When low concentrations of surfactants or no surfactant were
      present in the oil phase, a condensed protein film was formed at the surface of
      the droplets, which was revealed by the irregular topology of the droplet surface
      viewed with contrast microscopy. At higher surfactant concentrations, this
      topology was not observed nor was the stability apparently affected; emulsion
      droplets coalesce immediately upon contact with each other. There seems to be a
      limiting surfactant concentration, which stabilizes the droplets toward fusion
      and prevents formation of a condensed surface film, when the droplets contain
      protein. The technique exhibits potential for examination of the effects of
      various excipients on the coalescence stability of emulsion droplets.

PMID- 15468334
TI  - Identification and characterization of inosine monophosphate dehydrogenase from
      Halobacterium salinarum.
AB  - Extremely halophilic Archaea, Halobacterium salinarum live in hypersaline
      habitats and maintain an osmotic balance of their cytoplasm by accumulating high
      concentrations of salt (mainly KCl). Therefore, their enzymes adapted to high
      NaCl concentrations offer a multitude of acutal or potential applications such as
      biocatalysts in the presence of high salt concentrations. In this study, the
      protein expression profile of H. salinarum cultured under different NaCl
      concentrations (3.5 M, 4.3 M, and 6.0 M) was investigated using two-dimensional
      gel electrophoresis (2-DE). As a result of 2-DE, the protein spots concentrated
      in acidic range at pH 3-10 were separated effectively using pH 3.5-4.5 ultrazoom
      IPG DryStrips. The proteins which proved to be upregulated or downregulated in 2
      DE gel were digested with trypsin and identified with matrix-assisted laser
      desorption/ionization-time of flight (MALDI-TOF) and electrospray ionization
      quadrupole (ESI-Q) TOF-mass spectrometry. Most proteins were identified as known
      annotated proteins based on sequence homology and few as unknown hypothetical
      proteins. Among proteins identified, an enzyme named inosine monophosphate
      dehydrogenase (IMPDH) was selected based on the possibility of its industrial
      application. IMPDH gene (1.6 kb fragment) expected to exist in H. salinarum was
      amplified by polymerase chain reaction (PCR) and expressed in Escherichia coli
      strain, BL21 (DE3) using a pGEX-KG vector. Recombinant IMPDH purified from H.
      salinarum has a higher activity in the presence of salt than in the absence of
      salt.

PMID- 15468335
TI  - Schwann cell is a target in ischemia-reperfusion injury to peripheral nerve.
AB  - Ischemia-reperfusion (IR) causes oxidative injury and ischemic fiber degeneration
      due to injury of the neuron and axon. In this study, we explore the effect of
      oxidative stress on Schwann cells, as a specific peripheral nerve target, using
      our established rat model for IR injury. Fifty-six rats were used. Six groups (N
      = 8 each) underwent complete hindlimb ischemia for 4 h, followed by reperfusion
      durations of 0 h, 3 h, 7 days, 14 days, 28 days, and 42 days. One group underwent
      sham operation (N = 8). We evaluated immunohistochemical labeling for oxidative
      injury using anti-8-hydroxydeoxyguanosine (8-OHdG). To identify cells committed
      to apoptosis, we studied immunolabeling to caspase-3 and terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL)
      positivity. Only minimal positivity was seen in the sham, 0-h, and 3-h groups.
      Positivity to 8-OHdG, caspase-3, and TUNEL increased significantly in groups
      undergoing longer reperfusion (8-OHdG, 7-28 days; caspase-3, 14-42 days; TUNEL,
      14-42 days). The positive cells surrounding axons were identified as being
      Schwann cells by their configuration and colabeling with S-100. We conclude that
      apoptosis of Schwann cells occurs during reperfusion and continues even when
      axons regenerate. Schwann cell apoptosis could contribute to impairment of axonal
      function and efficiency of fiber regeneration. Both these abnormalities are known
      to occur in experimental and human diabetic nerves.

PMID- 15468336
TI  - Regeneration of adult rat spinal cord is promoted by the soluble KDI domain of
      gamma1 laminin.
AB  - Regeneration in the central nervous system (CNS) of adult mammals is hampered by
      formation of a glial scar and by proteins released from the myelin sheaths of
      injured neuronal pathways. Our recent data indicate that the KDI (Lys-Asp-Ile)
      domain of gamma1 laminin neutralizes both glial- and myelin-derived inhibitory
      signals and promotes survival and neurite outgrowth of cultured human spinal cord
      neurons. We show that after complete transection of the adult rat spinal cord,
      animals receiving onsite infusion of the KDI domain via osmotic mini-pumps
      recover and are able to sustain their body weights and walk with their hindlimbs.
      Animals treated with placebo suffer from irreversible hindlimb paralysis.
      Microscopic and molecular analyses of the spinal cords indicate that the KDI
      domain reduces tissue damage at the lesion site and enables neurite outgrowth
      through the injured area to effect functional recovery of the initially paralyzed
      animals. That the KDI domain enhances regeneration of acute spinal cord injuries
      in the adult rat suggests that it may be used to promote regeneration of spinal
      cord injuries in humans.

PMID- 15468337
TI  - Effects of prednisone in canine muscular dystrophy.
AB  - Glucocorticoid use may provide short-term functional improvement in boys with
      Duchenne muscular dystrophy (DMD). We report functional and histopathologic
      changes following a 4-month course of daily oral prednisone in a canine model of
      DMD, termed golden retriever muscular dystrophy (GRMD). Muscle extension forces
      in GRMD dogs treated daily with 1 and 2 mg/kg prednisone measured 2.349 +/- 0.92
      and 3.486 +/- 0.67 N/kg, respectively, compared to 1.927 +/- 0.63 N/kg in
      untreated GRMD controls (p < 0.05 for 2 mg/kg group); GRMD muscle flexion forces
      measured 0.435 +/- 0.13 and 0.303 +/- 0.08 N/kg, respectively, compared to 0.527
      +/- 0.01 N/kg in untreated GRMD controls (p < 0.05 for both groups). Although
      cranial sartorius hypertrophy and tibiotarsal joint angles also tended to
      improve, myofiber calcification increased and fetal myosin expression decreased
      following prednisone. Thus, functional data indicate benefit but histopathologic
      changes following prednisone treatment in GRMD suggest possible deleterious
      consequences.

PMID- 15468338
TI  - Quadriceps fatigue caused by catchlike-inducing trains is not altered in old age.
AB  - The relative loss of peak force from electrical stimulation protocols has
      provided inconsistent results when used to compare muscle fatigability between
      young and old adults. In addition to the effect of task on these comparisons, age
      related alterations in the development and relaxation of force are possible
      factors that have not been considered. The purposes of this study were to compare
      the fatigability of the quadriceps of young (26.7 +/- 1.0 years) and old men
      (78.3 +/- 1.3 years), as assessed by changes in peak force, force time integral
      (FTI), and half-relaxation time (HRT), during intermittent electrical stimulation
      protocols, and to determine whether manipulation of the activation frequency
      affected the comparisons. Fatigue was caused by constant-frequency (CF), and
      catchlike-inducing (CI) train protocols, both of which consisted of intermittent
      trains (6 pulses on: 650 ms off) of stimulation. After each protocol, the force
      generating capacity of the fatigued muscle was assessed with three trains of
      stimuli: a CF train, a CI train and a 1-s 50-HZ train. There was no effect of age
      on the loss of peak force or the development of low-frequency fatigue induced by
      either protocol. Conversely, irrespective of the protocol, the FTI was better
      maintained by approximately 9% in the old than young men. Because peak force did
      not differ between groups during fatigue, it is likely that the FTI was preserved
      by the exacerbated slowing of HRT in the quadriceps of the old men. The results
      confirm an apparent paradox between muscle fatigue and stimulation with CI
      trains: a single CI train produces greater force than a CF train in a fatigued
      muscle, but there is greater fatigue induced by repetitive CI than CF train
      stimulation. Old age did not affect this fatigue paradox.

PMID- 15468339
TI  - Stability of leukemia-associated aberrant immunophenotypes in patients with acute
      myeloid leukemia between diagnosis and relapse: comparison with cytomorphologic,
      cytogenetic, and molecular genetic findings.
AB  - BACKGROUND: Multiparameter flow cytometry is increasingly used to monitor minimal
      residual disease in patients with acute myeloid leukemia to identify leukemic
      cells by leukemia-associated aberrant immunophenotypes (LAIPs). Changes in LAIPs
      during the course of the disease may be a limitation for this approach. METHODS:
      We analyzed 49 patients at diagnosis and relapse by flow cytometry,
      cytomorphology, cytogenetics, and molecular genetics. RESULTS: In 37 patients
      (76%), at least one LAIP detectable at diagnosis was present at relapse; in 12
      patients (24%), none of the original LAIPs were present in at least 1% of bone
      marrow cells. Three groups were identified: no change in LAIPs, partial changes
      in LAIPs, and complete change in LAIPs. There were significant differences across
      these groups with regard to changes in cytomorphology (11%, 40%, and 58% of all
      cases, respectively; P = 0.007), cytogenetics (15%, 20%, and 25%; not
      significant), and molecular genetics (18%, 0, and 86%; P = 0.002). CONCLUSIONS:
      These data indicate that, in a subset of patients with acute myeloid leukemia,
      the disease is biologically different at relapse; therefore, monitoring of
      minimal residual disease is difficult to accomplish. In most patients with acute
      myeloid leukemia, multiparameter flow cytometry may be used to monitor minimal
      residual disease.

PMID- 15468340
TI  - Effects of velocity on maximal torque production in poststroke hemiparesis.
AB  - Impaired torque production is a major physical impairment following stroke, and
      has been studied extensively in isometric conditions. However, functional use of
      a limb requires torque production during movement, and the effects of velocity on
      maximal torque production may be abnormally enhanced in the paretic limb. The
      purpose of this study was to quantify the effects of movement velocity on maximal
      torque production during isokinetic, concentric flexion and extension of the
      elbow in poststroke subjects. Three speeds were tested (30, 75, 120 deg/s) over a
      100-deg range of motion. To control for strength variations between subjects and
      limbs, isokinetic torques were normalized by peak isometric torque. As flexion
      velocity increased, paretic limb torque decreased at a greater rate than in the
      unaffected limb. During extension, paretic limb torque was much lower than torque
      in the unaffected limb at all speeds. In both flexion and extension, the
      disparity between limbs in the constant-velocity torque-angle curves became more
      pronounced as velocity increased. Torque decreased 44% +/- 7% in flexion and 63%
      +/- 9% in extension as velocity increased from 30 to 120 deg/s, whereas the
      corresponding decreases in the unaffected limb were only 9% +/- 5% in flexion and
      16% +/- 4% in extension. No electromyographic (EMG) abnormalities were observed
      during flexion. During extension, EMG data provided evidence for abnormally
      increased antagonist coactivation in brachioradialis and markedly reduced
      activation in triceps as potential contributors to the decreased extension
      torques. The finding that movement velocity produces large deficits in maximal
      torque might explain why functional use of the paretic limb is often impaired
      even though isometric strength appears adequate.

PMID- 15468341
TI  - Neuropathy associated with lansoprazole treatment.

PMID- 15468342
TI  - Predicting psychological distress in college students: the role of rumination and
      stress.
AB  - Psychological distress among college students represents a serious health
      concern. The aim of this research was to investigate, for the first time, whether
      interactions between rumination and different measures of stress could
      differentially predict components of psychological distress, within a diathesis
      stress framework. This self-report study employed a longitudinal design, spanning
      a period of 6 months. One hundred sixty-one undergraduate college students
      completed selected measures of psychological distress, rumination, and stress at
      two time points 6 months apart. Both independent and interaction effects were
      examined through hierarchical regression analyses. Rumination and stress were
      found to interact significantly to predict the social dysfunction components of
      psychological distress. Other main effects are reported. The evidence supported
      the proposed diathesis-stress model and extended previous research by relating
      rumination to different components of psychological distress prospectively.

PMID- 15468343
TI  - Media violence exposure and executive functioning in aggressive and control
      adolescents.
AB  - The relationship between media violence exposure and executive functioning was
      investigated in samples of adolescents with no psychiatric diagnosis or with a
      history of aggressive-disruptive behavior. Age-, gender-, and IQ-matched samples
      of adolescents who had no Diagnostic and Statistical Manual of Mental Disorders
      fourth edition (DSM-IV; American Psychiatric Association, 1994) diagnosis (N =
      27) and of adolescents who had DSM-IV Disruptive Behavior Disorder diagnoses (N =
      27) completed measures of media violence exposure and tests of executive
      functioning. Moderate to strong relationships were found between higher amounts
      of media violence exposure and deficits in self-report, parent-report, and
      laboratory-based measures of executive functioning. A significant diagnosis by
      media violence exposure interaction effect was found for Conners' Continuous
      Performance Test scores, such that the media violence exposure-executive
      functioning relationship was stronger for adolescents who had Disruptive Behavior
      Disorder diagnoses. Results indicate that media violence exposure is related to
      poorer executive functioning, and this relationship may be stronger for
      adolescents who have a history of aggressive-disruptive behavior.

PMID- 15468344
TI  - An efficient therapeutic approach to patients with acute promyelocytic leukemia
      using a combination of arsenic trioxide with low-dose all-trans retinoic acid.
AB  - The use of arsenic trioxide (As2O3, ATO) combined with all-trans retinoic acid
      (ATRA) has recently been reported to induce remission in patients with acute
      promyelocytic leukemia (APL). However, its efficiency remains inconclusive mainly
      due to the small number of the available cases. In this study, therefore, we
      present a clinical study using a combination of ATO with low-dose ATRA (LD-ATRA)
      to treat 108 APL patients (80 newly diagnosed patients, 28 relapsed patients).
      Therapeutic outcomes using the ATO/LD-ATRA approach were compared with those of
      APL patients treated either with ATO alone (65 patients) or ATRA alone (51
      patients). The results showed that the ATO/LD-ATRA approach provided
      significantly better therapeutic outcomes as compared to either ATO or ATRA
      alone, as evidenced by lower mortality, a higher CR rate and a reduced period to
      CR. In addition, the toxic side-effects have been no worse with the combined
      ATO/LD-ATRA treatment than with either ATO or ATRO alone and in some cases have
      been reduced. These data suggest that the ATO/LD-ATRA regimen is superior to
      either regimen given alone to patients with APL.

PMID- 15468345
TI  - How the psychotherapy research community must work toward measurement validity
      and why.
AB  - The clinical and the scientific value of the whole psychotherapy research
      enterprise depends upon the construct validity of its Mental Health Status (MHS)
      measurements. This is essentially a matter of conceptual validity, that is, what
      we agree that MHS reasonably means. Any theory of psychotherapy can be true only
      insofar as it involves independent variables that have demonstrated causal
      relevance to such conceptually valid measurements of MHS, which is also what
      makes the measurements of these independent variables predictively valid. Every
      published efficacy, effectiveness, and case study that tests or explores for
      explanations of MHS ought to involve the same conceptually valid MHS measures,
      but the necessary validity is still undemonstrated. It cannot be demonstrated
      unless the research community reaches a conceptual consensus on MHS, a consensus
      that decisive psychotherapy research must await.

PMID- 15468346
TI  - Power of the database: an international approach to studying longterm rheumatoid
      arthritis therapy.

PMID- 15468347
TI  - The evolving use of tumor necrosis factor inhibitors in rheumatoid arthritis.

PMID- 15468348
TI  - Tumor necrosis factor-alpha blockade and the risk of vasculitis.

PMID- 15468349
TI  - Topical nonsteroidal antiinflammatory drugs are effective in osteoarthritis of
      the knee.

PMID- 15468350
TI  - Fatigue assessments in rheumatoid arthritis: comparative performance of visual
      analog scales and longer fatigue questionnaires in 7760 patients.
AB  - OBJECTIVE: Fatigue has been recognized as an important domain in rheumatoid
      arthritis (RA) clinical trials and in patient care and outcome. However, lengthy
      fatigue questionnaires cannot be easily used in clinical care, and there are no
      data for the comparative performance of various short and long questionnaires. We
      compared a single-item visual analog scale (VAS) with 3 longer fatigue
      questionnaires, investigating 4 fatigues scales: the Multi-dimensional Assessment
      of Fatigue (MAF), the vitality scale from the Medical Outcomes Study Short Form
      36 (SF-36), the Brief Fatigue Inventory (BFI), and the VAS. METHODS: Participants
      in a longitudinal outcome study of RA (N = 7760) completed the 4 questionnaires,
      and a subset of 5155 completed the same fatigue scales 6 months later. RESULTS:
      All questionnaires were highly correlated and were correlated at similar levels
      with clinical variables. The 3 longer questionnaires had slightly greater
      reliability in cross-sectional analyses, but the VAS was as good as or better
      than the longer questionnaires when sensitivity to change was considered.
      CONCLUSION: The single item VAS performs as well as or better than longer scales
      in respect to sensitivity to change, and is at least as well correlated with
      clinical variables as longer scales. The VAS fatigue scale is suitable for
      routine use in clinical care, an advantage that is lacking for the other scales.
      These results do not indicate advantages for longer fatigue scales compared with
      the VAS.

PMID- 15468351
TI  - Can gold therapy be used more safely in rheumatoid arthritis? Adverse drug
      reactions are more likely in patients with nodular disease, independent of HLA
      DR3 status.
AB  - OBJECTIVE: . To investigate whether features associated with severe rheumatoid
      arthritis (RA) are predictive of adverse drug reactions (ADR) to gold salts,
      independent of HLA-DR3 status. METHODS: A cohort of patients with RA (n = 41) who
      developed thrombocytopenia (platelets < 100 10(6)/l) or proteinuria (> 1.0 g/24
      h) upon treatment with gold sodium thiomalate was identified from patient records
      and matched for age, sex, and disease duration with 41 RA controls treated with
      gold without development of ADR. A second group of 161 random RA patients that
      had received gold therapy for at least as long without development of an ADR was
      also compared. All patients were typed for HLA-DRB1, and the presence of
      rheumatoid factor (RF), antinuclear antibodies (ANA), and nodules before
      initiation of therapy was recorded. Association of clinical or genetic factors
      with ADR was investigated using the McNemar test and logistic regression
      analysis. RESULTS: Patients with ADR were more likely to have nodular disease
      than their matched controls (51.3% vs 25.6%; odds ratio, OR = 3.0, p = 0.02) and
      more likely to be HLA-DR3 positive (41.2% vs 17.6%; OR = 3.0, p = 0.045). No
      difference between the groups was found for RF or ANA. Nodular disease was
      associated with development of ADR independently of HLA-DR3, although a
      combination of both factors significantly increased the likelihood of an ADR.
      CONCLUSION: Our data suggest that nodular disease may be a predictor of gold
      induced ADR independent of HLA-DR3.

PMID- 15468352
TI  - Adverse events with disease modifying antirheumatic drugs (DMARD): a cohort study
      of leflunomide compared with other DMARD.
AB  - OBJECTIVE: To determine and compare the incidence of serious adverse events (AE)
      during treatment of rheumatoid arthritis (RA) with disease modifying
      antirheumatic drugs (DMARD), focusing on leflunomide (LEF). METHODS: A
      retrospective cohort study of a large US insurance claims database was performed.
      Study groups were patients with RA classified by DMARD exposure as either no
      DMARD therapy, single-agent DMARD (monotherapy), or combination-DMARD therapy.
      Specific DMARD examined were leflunomide (LEF) and methotrexate (MTX), compared
      to other DMARD (penicillamine, hydroxychloroquine, sulfasalazine, gold,
      etanercept, infliximab) and no DMARD (nonsteroidal antiinflammatory drugs, COX-2
      inhibitors). All AE reported were considered endpoints; primary endpoints
      included hepatic, dermatologic, hematologic, infectious, respiratory,
      hypertension, and pancreatitis AE. RESULTS: The 40,594 RA patients of the study
      period (September 1998 to December 2000) accumulated 83,143 person-years (PY) of
      followup. Followup for each of the groups was: DMARD-monotherapy, 46,054 PY (55%
      of total); combination-DMARD, 25,830 PY (14%); and no-DMARD, 11,259 PY (14%). The
      incidence rate of all AE combined was significantly lower for LEF monotherapy (94
      events/1000 PY) than MTX (145 events/1000 PY), other DMARD (143 events/1000 PY),
      or no DMARD (383 events/1000 PY) (p < 0.001 for all comparisons). The "all-AE"
      rates during combination therapy with LEF + MTX (43/1000 PY) and LEF + other
      DMARD (59/1000 PY) were lower than the "all-AE" rate for DMARD + MTX (70/1000 PY;
      p = 0.002). LEF monotherapy had the lowest rate of hepatic events in the DMARD
      monotherapy groups. CONCLUSION: The rates of AE in the LEF group, alone and
      combined with MTX, were generally lower than or comparable to the AE rates seen
      with MTX and other agents.

PMID- 15468353
TI  - Infusion-related reactions to infliximab in patients with rheumatoid arthritis in
      a clinical practice setting: relationship to dose, antihistamine pretreatment,
      and infusion number.
AB  - OBJECTIVE: We describe infusion-related reactions to infliximab (during infusion
      or within 1 hour postinfusion) in patients with active rheumatoid arthritis (RA)
      treated in a quaternary care center. METHODS: We followed 113 patients for a mean
      of 60.6 +/- 28.9 weeks, obtaining 10.5 +/- 4.9 infusions per patient. RESULTS: We
      observed 1183 infusions resulting in 104 infusion reactions (8.8%). All reactions
      resolved within several hours following cessation of the infusion and none was
      serious enough to warrant hospitalization. Reactions included allergic reactions
      (pruritus, urticaria) in 4.2% of infusions, cardiopulmonary (hypotension,
      hypertension, tachycardia) in 3.0%, and miscellaneous reactions (headache,
      nausea, vomiting) in 2.0%. Reactions occurred in 8.0% of 3 mg/kg infusions and in
      10.3% of 5 mg/kg infusions. Reactions occurred in 13.2% of infusions that
      involved antihistamine pretreatment compared to only 7.5% of infusions that
      involved no pretreatment. At both infliximab doses, there was a similar frequency
      of infusion reactions in patients pretreated due to a previous infusion (12.6%)
      compared to those pretreated strictly based on infusion number (14.7%). A number
      of the reactions involving antihistamine pretreatment may be explained by known
      side effects of diphenhydramine, including headache, dizziness, nausea, and
      palpitations. CONCLUSION: Infusion-related reactions to infliximab were
      infrequent, rarely severe, and easily manageable. The frequency of reactions was
      equivalent in patients treated with 3 mg/kg compared to 5 mg/kg. Reactions were
      significantly more frequent in infusions where patients were pretreated with the
      antihistamine diphenhydramine, compared to those not involving pretreatment.

PMID- 15468354
TI  - Multisegment foot motion during gait: proof of concept in rheumatoid arthritis.
AB  - OBJECTIVE: To test a multisegment foot model for kinematic analysis during
      barefoot walking in patients with well established rheumatoid arthritis (RA) and
      foot impairments. METHODS: Five healthy adult subjects and 11 RA patients with
      advanced disease were studied. Foot impairments were assessed using standardized
      outcomes and clinical examination techniques. A 6-camera 60 Hz video-based motion
      analysis system was used to measure motion of the shank, rearfoot, forefoot, and
      hallux segments and the vertical displacement of the navicular. Face validity and
      estimates of repeatability were determined. Motion patterns were calculated and
      comparisons were made between healthy subjects and patients with RA.
      Relationships between clinical impairment and abnormal motion were determined
      through inspection of individual RA cases. RESULTS: Across the motion variables,
      the within-day and between-day coefficient of multiple correlation values ranged
      from 0.677 to 0.982 for the healthy subjects and 0.830 to 0.981 for RA patients.
      Based on previous studies, motion parameters for the healthy subjects showed
      excellent face validity. In RA patients, there was reduced range of motion across
      all segments and all planes of motion, which was consistent with joint stiffness.
      In the RA patients, rearfoot motion was shifted towards eversion and external
      rotation and peak values for these variables were increased, on average, by 7
      degrees and 11 degrees, respectively. Forefoot range of motion was reduced in all
      3 planes (between 31% and 53%), but the maximum and minimum angles were
      comparable to normal. The navicular height, during full foot contact, was on
      average 3 mm lower in the RA patients in comparison to normal. The hallux was
      less extended in the RA subjects in comparison to normal (21 degrees vs 33
      degrees) during the terminal stance phase. Individual cases showed abnormal
      patterns of motion consistent with their clinical impairments, especially those
      with predominant forefoot pain or pes planovalgus. CONCLUSION: In RA,
      multisegment foot models may provide a more complete description of foot motion
      abnormalities where pathology presents at multiple joints, leading to complex and
      varied patterns of impairment. This technique may be useful to evaluate
      functional changes in the foot and to help plan and assess logical, structurally
      based corrective interventions.

PMID- 15468355
TI  - Occupational risk factors for the development of systemic lupus erythematosus.
AB  - OBJECTIVE: There have been few studies of occupational exposures and systemic
      lupus erythematosus (SLE). We examined the association between the risk of SLE
      and occupational exposures (mercury, solvents, and pesticides), specific jobs
      (ever worked in teaching, healthcare, and cosmetology), and working night or
      rotating shifts. METHODS: Patients with recently diagnosed SLE (n = 265) were
      recruited through 4 university based and 30 community based rheumatology
      practices in North Carolina and South Carolina, USA. Controls (n = 355) were
      identified through driver's license records and were frequency matched to
      patients by age, sex, and state. Data collection included an in-person interview
      with detailed farming and work histories. RESULTS: Associations were seen with
      self-reported occupational exposure to mercury (OR 3.6, 95% CI 1.3, 10.0), mixing
      pesticides for agricultural work (OR 7.4, 95% CI 1.4, 40.0), and among dental
      workers (OR 7.1, 95% CI 2.2, 23.4). Although these associations were fairly
      strong and statistically significant, the prevalence of these exposures was very
      low and thus these estimates are based on a small number of exposed cases and
      controls. Weaker associations were seen between SLE and shift work (OR 1.6, 95%
      CI 0.99, 2.7) and among healthcare workers with patient contact (OR 1.7, 95% CI
      0.99, 2.9). There was no association of SLE with use of solvents or among
      teachers or cosmetologists. CONCLUSION: This study reveals the potential
      contribution of occupational exposures to the development of SLE, and highlights
      some exposures and experiences that should be examined in other studies using
      more extensive exposure assessment techniques and in experimental studies of
      autoimmunity.

PMID- 15468356
TI  - The Systemic Lupus Activity Measure-revised, the Mexican Systemic Lupus
      Erythematosus Disease Activity Index (SLEDAI), and a modified SLEDAI-2K are
      adequate instruments to measure disease activity in systemic lupus erythematosus.
AB  - OBJECTIVE: To assess the validity, reliability, and feasibility of the Systemic
      Lupus Activity Measure-Revised (SLAM-R), the Mexican version of the Systemic
      Lupus Erythematosus Disease Activity Index (MEX-SLEDAI), and a Modified SLEDAI
      2000 (SLEDAI-2K) compared with the SLEDAI-2K in a multiethnic population of
      patients with SLE. METHODS: We studied 92 SLE patients from 3 US geographic areas
      (Alabama, Texas, and Puerto Rico). Assessment occurred during regular outpatient,
      inpatient, or study encounters. A trained physician scored the 4 instruments and
      also assessed disease activity globally [physician global assessment (PGA)].
      Convergent (with SLEDAI-2K) and construct validity (with PGA) were determined by
      Spearman rank (rs) correlation test. Level of agreement between the instruments
      was assessed using Bland-Altman plots. Discriminant validity (distinguishing
      clearly active vs mildly/nonactive disease) was assessed considering the SLEDAI
      2K (and the PGA) as the gold standard. Feasibility was explored by cost analyses.
      RESULTS: The SLAM-R, the MEX-SLEDAI, and the Modified SLEDAI-2K were highly
      correlated with the SLEDAI-2K (rs = 0.566, 0.755, 0.924, respectively) and with
      the PGA (rs = 0.650, 0.540, 0.634, respectively). The 3 instruments showed good
      agreement with the SLEDAI-2K (Bland-Altman plots). The Modified SLEDAI-2K had
      better discriminant validity than the SLAM-R and the MEX-SLEDAI. The Modified
      SLEDAI-2K was the least expensive instrument. CONCLUSION: The SLAM-R, the MEX
      SLEDAI, and the Modified SLEDAI-2K are adequate options for assessment of SLE
      disease activity; they are also less costly than the SLEDAI-2K.

PMID- 15468357
TI  - High prevalence of right ventricular systolic dysfunction in early systemic
      sclerosis.
AB  - OBJECTIVE: To assess right ventricular (RV) function in patients with early
      systemic sclerosis (SSc) and the acute effects of calcium channel blockers on RV
      ejection fraction (RVEF). METHODS: Forty-two consecutive patients with SSc with
      less than 5 years' disease duration and normal pulmonary arterial pressure (35
      women, 7 men; mean age 54.3 +/- 9.7 years; 16 with diffuse and 26 with limited
      cutaneous forms, systolic pulmonary arterial pressure 30.3 +/- 5.4 mmHg) were
      prospectively evaluated. All underwent pulmonary function testing,
      echocardiography, and radionuclide ventriculography at rest and 2 hours after
      receiving 40 mg oral nicardipine, and were compared at baseline with 20 gender
      and age matched controls. RESULTS: None of the patients with SSc had clinical
      evidence of heart failure. At baseline, SSc patients had significantly lower LVEF
      (68.5% +/- 7.9 vs 72.4% +/- 5.0, p = 0.049) and RVEF (36.5% +/- 7.0 vs 45.8% +/-
      5.7, p < 0.0001). Sixteen patients had reduced RVEF (< 35%), 3 had reduced LVEF
      (< 55%), and 10 had reduced peak filling rate (PFR). RVEF correlated to both LVEF
      and PFR (r = 0.64, p < 0.0001, and r = 0.36, p = 0.0037, respectively), whereas
      no correlation was found with pulmonary function impairment or pulmonary arterial
      pressure. Nicardipine resulted in a significant increase in RVEF (from 36.5% +/-
      7.0 to 42.3% +/- 8.4, p < 0.001) whereas afterload indicated by mean arterial
      pressure did not differ significantly. CONCLUSION: Reduced RVEF appears to be a
      common feature in early SSc; it may be due to intrinsic myocardial involvement
      and is acutely improved by nicardipine.

PMID- 15468358
TI  - Autocrine activation by interleukin 1alpha induces the fibrogenic phenotype of
      systemic sclerosis fibroblasts.
AB  - OBJECTIVE: To explore the cellular localization of interleukin 1alpha (IL-1alpha)
      in cultured fibroblasts from lesional skin of patients with systemic sclerosis
      (SSc) and to study the role of intracellular IL-1alpha in the activation of
      fibroblasts. METHODS: Dermal fibroblasts were derived from 12 patients with SSc.
      Expression of IL-1alpha mRNA was examined using reverse transcriptase-polymerase
      chain reaction (RT-PCR). The cellular distribution of IL-1alpha was examined by
      subcellular fractionation, flow cytometry, and immunocytochemistry. A full-length
      IL-1alpha cDNA was subcloned into the pcDNA3 vector to create sense and antisense
      encoding constructs. Normal and SSc fibroblasts were stably transfected with the
      sense and antisense-encoding constructs, respectively. Stably transfected
      fibroblast clones were analyzed for the production of procollagen and IL-6
      protein by ELISA, alpha1(I) procollagen mRNA by Northern blot hybridization, and
      proliferation by [3H]thymidine incorporation. RESULTS: SSc-affected fibroblasts
      constitutively expressed intracellular IL-1alpha, which was predominantly located
      in the nucleus. Inhibition of IL-1alpha expression in SSc-affected fibroblasts
      using antisense constructs resulted in decreased proliferation, IL-6 production,
      and procollagen synthesis. Conversely, overexpression of IL-1alpha in normal
      fibroblasts resulted in development of the SSc fibroblast phenotype. CONCLUSION:
      IL-1alpha is an important autocrine fibrogenic factor in SSc, suggesting that
      inhibition of intracellular IL-1alpha may be a novel strategy for the treatment
      of SSc.

PMID- 15468359
TI  - Leukocytoclastic vasculitis associated with tumor necrosis factor-alpha blocking
      agents.
AB  - OBJECTIVE: To describe the clinical features of leukocytoclastic vasculitis (LCV)
      associated with the use of tumor necrosis factor-alpha (TNF-alpha) blockers.
      METHODS: The Adverse Events Reporting System (AERS) of the US Food and Drug
      Administration (FDA) was queried for reports of patients who developed LCV during
      or after starting etanercept or infliximab from date of approval of each agent
      through September 6, 2002. RESULTS: Thirty-five cases of LCV were identified, 20
      following etanercept administration and 15 following infliximab administration.
      Seventeen of the 35 (48.5%) were biopsy-proven cases and the others had skin
      lesions that were clinically typical for LCV. Twenty-two of 35 (62.8%) patients
      had complete or marked improvement of skin lesions upon stopping the TNF-alpha
      blocker. Three patients who had received etanercept had continuing lesions
      despite discontinuation of the drug; one of these patients improved when switched
      to infliximab. One patient who received infliximab was reported to have
      continuing lesions despite discontinuation of the drug and treatment with
      prednisone and antihistamines. Six patients experienced a positive rechallenge
      (recurrence of LCV on restarting therapy with a TNF-alpha blocker) and 3 patients
      a negative rechallenge phenomenon. LCV lesions improved in patients despite
      continuing use of concomitant medications reportedly associated with LCV.
      CONCLUSION: Therapy with TNF-alpha blocking agents may be associated with the
      development of LCV. Skin lesions improved on discontinuation of anti-TNF-alpha
      therapy in most patients. Other causes of LCV should be excluded, and evaluation
      for systemic involvement with appropriate investigations is recommended.

PMID- 15468360
TI  - Analysis of CARD15 polymorphisms in Korean patients with ankylosing spondylitis
      reveals absence of common variants seen in western populations.
AB  - OBJECTIVE: Substantial epidemiological and genetic evidence suggests that
      ankylosing spondylitis (AS) is likely due to an interplay of genetic and
      environmental factors. Recently, CARD15, located in chromosome 16q12, has been
      established as a disease susceptibility gene for Crohn's disease, Blau syndrome,
      and possibly psoriatic arthritis. Association studies in admixed populations from
      Northern European ancestry noted no such association between CARD15 mutations and
      AS. However, a homogenous population has yet to be studied. We investigated the
      prevalence of the 3 common CARD15 variants in a homogenous Korean population with
      AS. METHODS: All subjects were native Koreans with AS satisfying the modified New
      York criteria. Korean controls were examined and confirmed to be unaffected by
      AS. Subjects with AS were genotyped for the R702W, G908R, and Leu1007fsinsC
      variants of CARD15 using mass array MALDI-TOF mass spectrometry. RESULTS: A total
      of 205 AS subjects and 200 controls were genotyped. No subject with AS had any
      variants at the 702 and 1007 sites of CARD15. Only one subject was heterozygous
      for the 908 variant. The overall genotype frequency in AS for any CARD15 variant
      was 0.5%. No control had any of the 3 CARD15 variants. CONCLUSION: Our findings
      indicate that the CARD15 gene is not a major contributor to AS susceptibility in
      the Korean population.

PMID- 15468361
TI  - CD8+ T cells oligoclonally expanded in synovial fluid at onset of
      spondyloarthropathy selectively proliferate in response to self-antigens:
      characterization of cell specificities in nonclonal populations.
AB  - OBJECTIVE: To characterize putative T cells responsible for the pathogenesis of
      spondyloarthropathies (SpA). METHODS: T cells from synovial fluid (SF) and
      peripheral blood lymphocytes from a patient with chronic ankylosing spondylitis
      and a patient at the onset of SpA were analyzed for the size of the ss-chain
      complementarity-determining region 3 to evaluate the degree of clonality. To
      assess their putative role in triggering disease, immortalized local T cells were
      tested in lymphocyte proliferation assays against a restricted panel of cell
      lines. RESULTS: At disease onset, expansions were detected only in the SF CD8+ T
      cell subset. As well, SF CD8+ T cells sharing an expanded clonotype (TCR-BV17
      J2S1) selectively proliferated when stimulated with autologous-presenting cells.
      The search for sequence similarities with the expanded clonotype revealed a high
      homology with the major clonotype in response to influenza A matrix peptide M58
      66. CONCLUSION: A CD8+ T cell-mediated antigen-driven mechanism seems to be
      responsible in the pathogenesis of SpA. Immune response to viral antigens (e.g.,
      from influenza) could be the initiating event in seronegative arthropathies. The
      combination of spectratyping with RT-PCR and specific Southern blot for the
      expanded clonotypes on cells derived from mixed lymphocyte cultures was useful to
      evaluate the proliferative responses of in vivo-expanded cells and to assess T
      cells involved in the pathogenesis of SpA.

PMID- 15468362
TI  - Doxycycline versus doxycycline and rifampin in undifferentiated
      spondyloarthropathy, with special reference to chlamydia-induced arthritis. A
      prospective, randomized 9-month comparison.
AB  - OBJECTIVE: Chlamydia is a known trigger of reactive arthritis (ReA). It may also
      be common cause of undifferentiated spondyloarthropathy (uSpA). Persistent,
      metabolically active, Chlamydiae have been observed in the synovial tissue of
      these patients years after their initial exposure. Trials with lymecycline and
      rifampin have shown benefit in early/acute Chlamydia-induced arthritis. In vitro
      data suggest that persistent Chlamydia become resistant to chronic monotherapy of
      tetracyclines or rifampin, whereas no such resistance is noted when rifampin is
      added to antimicrobials that are active against Chlamydia. Rifampin and
      doxycycline also show synergistic effect against Chlamydia. In addition, rifampin
      inhibits chlamydial production of heat shock proteins (HSP). HSP60 plays a key
      role in the chronic persistent state of Chlamydia. We conducted a prospective,
      randomized 9-month trial to evaluate the efficacy of doxycycline versus a
      combination of doxycycline and rifampin in the treatment of uSpA. METHODS: The
      study enrolled 30 patients with chronic inflammatory arthritis (average disease
      duration 10 yrs) who fulfilled the European Spondylarthropathy Study Group
      criteria, with no evidence of inflammatory bowel disease, psoriasis, ankylosing
      spondylitis, or preceding dysentery. Patients received doxycycline 100 mg po
      twice daily or a combination of doxycycline 100 mg po twice daily and rifampin
      600 mg po daily. They received a 4-question self-questionnaire and a blinded
      joint examination at each visit. The questions include a visual analog scale
      (VAS) for their current amount of back pain, duration of morning stiffness, back
      pain at night, and peripheral joint pain. The blinded joint examination consisted
      of a swollen joint count (SJC) and a tender joint count (TJC). These 6 variables
      were assessed at baseline and at 1, 3, 6, and 9 months. Responders were defined
      as those who improved > or = 20% in at least 4 of the 6 variables at 9 months of
      therapy. RESULTS: Comparing the doxycycline + rifampin arm (D/R) versus the
      doxycycline arm (D) at 9 months of therapy, all 6 variables improved more in D/R
      versus D, 4 of which were statistically significant. The mean VAS (scale of 100)
      decreased 24.4 points in D/R in contrast to 3 points in D (p < 0.03). Duration of
      morning stiffness decreased by 1.2 h in D/R, with a slight increase of 0.1 h in D
      (p < 0.003). The back pain at night and peripheral joint pain both improved in
      D/R group versus D (not statistically significant). Finally, the SJC and TJC also
      improved in D/R (-2.1 and -2.5) versus D (-0.4 and -0.6; p = 0.02, p = 0.03,
      respectively). Eleven of 15 patients in the D/R arm were responders, whereas only
      2 of 15 D group patients were considered responders (p < 0.003). CONCLUSION: The
      combination of doxycycline and rifampin for 9 months seemed to be effective in
      treatment of chronic uSpA. This is the first study to demonstrate therapeutic
      benefit with antimicrobials to a chronic inflammatory arthritis possibly
      secondary to persistent Chlamydia.

PMID- 15468363
TI  - Clinical vertebral fractures in patients with ankylosing spondylitis.
AB  - OBJECTIVE: To evaluate the prevalence and characteristics of clinically confirmed
      vertebral fractures (CVF) in patients with ankylosing spondylitis (AS). METHODS:
      Coordinated by the Ankylosing Spondylitis International Federation in Germany and
      in Denmark, a self-administered questionnaire was sent to all their members about
      age, diagnosis, disease duration, HLA-B27 status, and history of CVF. Patients
      who were aware of having had a CVF were asked to return the questionnaire with
      additional specification of the location of CVF, associated trauma, neurological
      complications, therapy for these complications, and recovery. We also reviewed
      available radiographs. RESULTS: Out of 15,097 questionnaires, 59 patients (0.4%)
      reporting 66 CVF returned the complete questionnaire (46 men, 13 women). Mean age
      at fracture was 50 +/- 9 years, after a mean duration of symptoms of 26 +/- 11
      years. CVF with wedging or crush or transverse fracture were reported in the
      cervical (n = 21, 36%), thoracic (n = 21, 36%), and lumbar spine (n = 16, 27%),
      with one unspecified. In 37 fractures (56%), patients reported no/low or medium
      trauma in relation to the fracture. In 31 fractures (47%), patients reported
      neurological complications, occurring mostly without trauma (n = 11, 35%) or
      after minimal trauma (n = 7, 23%). Twenty (65%) of these patients did not have
      full neurological recovery. CONCLUSION: We found that 0.4% of patients with AS
      reported CVF at a mean age of 50 years, occurring after 2 decades of disease,
      mainly without trauma or after minimal trauma, with frequent neurological
      complications mostly followed by incomplete neurological recovery.

PMID- 15468364
TI  - Increasing mineral density after menopause in individual lumbar vertebrae as a
      marker for incident degenerative disease: a pilot study for the effects of body
      composition and diet.
AB  - OBJECTIVE: To investigate the potential utility of dual x-ray absorptiometry
      (DXA) in incidence studies of lumbar spinal spondyloarthropathy. METHODS: Fifty
      eight women recruited after menopause to a study of spinal bone loss were
      measured every 2 years for over a decade. Five developed scan image evidence of
      patchy calcification and 10 developed statistically significant (p < 0.05)
      nonparallelism of their bone loss (or gain) in L2, L3, and L4. The number of
      years since menopause at which these abnormal calcification trends (ACT) occurred
      was made the outcome in Cox proportional hazard modeling. At baseline, diet was
      assessed twice using 3-day weighed intakes. Nutrients estimated included
      carbohydrate, fat, protein, fiber, calcium and other minerals, and 6 vitamins.
      Measurements at baseline of fat mass and other anthropometric variables were
      made. RESULTS: The best single explanatory variable for developing ACT was whole
      body fat mass. Dietary fat was also predictive (p = 0.05) and adding dietary
      vitamin D (obtained substantially from oily fish) as a second predictor improved
      the diet model further (to p = 0.006 for model). These 2 dietary variables
      remained significantly predictive when fat mass was adjusted for (p = 0.0003 for
      model). CONCLUSION: Serial DXA measurements of the lumbar spine have the
      potential to provide a new, low radiation-dose approach to early identification
      of localized abnormal spinal calcification in epidemiology and trials. Alongside
      body fat, dietary fat intake and its components may warrant further investigation
      as risk factors for incident degenerative disease of the spine.

PMID- 15468365
TI  - Are there differences between men and women prescribed bisphosphonate therapy in
      canadian subspecialty osteoporosis practices?
AB  - OBJECTIVE: To determine if there are differences between men and women referred
      for treatment of osteoporosis in Canada. METHODS: We performed an observational
      study of 1588 patients (163 men, 1425 women), 50 years of age and older, who were
      prescribed cyclic etidronate or alendronate for treatment of osteoporosis or
      osteopenia and had at least 2 years of followup registered in the Canadian
      Database for Osteoporosis and Osteopenia Patients (CANDOO). Comparisons of
      characteristics between men and women were performed using Pearson chi-square
      test, Student's t test, or a Kruskal-Wallis test, whichever was most appropriate.
      RESULTS: Mean baseline femoral neck and lumbar spine bone mineral densities were
      significantly higher in men than women at both the femoral neck and lumbar spine
      (p < 0.05, respectively). Men had double the rate of prevalent vertebral
      fractures (44%, 72/163) compared to women (22%, 315/1425; p < 0.001) and triple
      the rate of multiple prevalent vertebral fractures (10%, 17/163) compared to
      women (3%, 37/1425, p < 0.001). Furthermore, men were twice as likely as women to
      sustain a fracture within 2 years of starting treatment during observation in the
      CANDOO study (men: 4%, 7/163, women: 2%, 24/1425, p = 0.033). CONCLUSION:
      Osteoporosis may be under-recognized in men until the condition is at an advanced
      stage. A form of gender bias may exist in recognition and treatment (or referral
      for treatment) of osteoporosis in men.

PMID- 15468366
TI  - Comparing the AUSCAN Osteoarthritis Hand Index, Michigan Hand Outcomes
      Questionnaire, and Sequential Occupational Dexterity Assessment for patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: The Australian Canadian Osteoarthritis Hand Index (AUSCAN), Michigan
      Hand Outcomes Questionnaire (MHQ), and the Sequential Occupational Dexterity
      Assessment (SODA) are assessments of hand function. Investigation of psychometric
      properties, administration, acceptability, and content of an assessment add
      strength to the findings of research and treatment. We evaluated the validity and
      reliability of the AUSCAN, MHQ, and the SODA for assessing disability in patients
      with rheumatoid arthritis (RA). METHODS: Sixty-two patients with RA completed the
      AUSCAN (visual analog scale version), the MHQ, and the SODA. Seventeen patients
      repeated the assessments within one week. RESULTS: The assessments recorded high
      variability within the sample of 62 patients with RA. The AUSCAN and MHQ provided
      patient and context-specific information, while the SODA provided more impairment
      information that could be readily compared between patients. Seventeen patients
      were tested twice within 5 days, showing good reliability of all assessments.
      Unlike the MHQ, AUSCAN and SODA do not provide information about individual hands
      or hand dominance. The physical function scales of the AUSCAN and the SODA were
      related (r = 0.81), and the AUSCAN and MHQ pain scales were related (r = 0.68).
      CONCLUSION: Clinicians and researchers should decide whether impairment, ability,
      or handicap outcome is the goal of assessment, and whether bilateral function or
      the function of one hand is of interest before choosing a hand assessment. The
      AUSCAN and MHQ are valid and reliable for assessment of hand disability in
      patients with RA, and they allow the patients to answer questions about their
      home environment. The SODA is also valid and reliable for assessing disability in
      a clinical situation that cannot be generalized to the home.

PMID- 15468367
TI  - Equivalence study of a topical diclofenac solution (pennsaid) compared with oral
      diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized
      controlled trial.
AB  - OBJECTIVE: . To compare the safety and efficacy of a topical diclofenac solution
      versus oral diclofenac in relieving the symptoms of primary osteoarthritis (OA)
      of the knee, in a randomized, double-blind, double-dummy equivalence trial.
      METHODS: A total of 622 men and women with radiological evidence of primary knee
      OA and mild to severe symptoms were randomly assigned to treatment with a topical
      diclofenac solution plus placebo oral capsules, or placebo topical solution plus
      oral diclofenac (50 mg) capsules. Patients applied 50 drops of study solution and
      took 1 study capsule 3 times daily for 12 weeks. Efficacy variables were pain and
      physical function, measured by the Western Ontario and McMaster Universities
      (WOMAC) VA 3.1 OA Index, and patient global assessment (PGA). Equivalence in the
      per-protocol group was based on previously defined ranges of clinically
      significant difference. Safety was assessed by evaluation of adverse events,
      vital signs, and laboratory data. RESULTS: The difference in mean (95% CI) change
      scores (final minus baseline) between treatments was 13.3 mm (-8.6 to 35.2) for
      pain (total scale 500 mm), 71.0 mm (-2.4 to 144.5) for physical function (total
      scale 1700 mm), and 4.3 mm (-1.2 to 9.8) for PGA (total scale 100 mm). The CI for
      each efficacy variable fell within the predefined equivalence ranges (pain, +/-
      75 mm; physical function, +/- 255 mm; PGA, +/- 20 mm), indicating that no
      clinically relevant difference was found between the 2 treatment arms. Safety
      analyses of patients applying topical diclofenac solution revealed some minor
      skin irritation at the application site--mostly skin dryness in 83/311 (27%)
      patients--but a significantly reduced incidence, relative to oral diclofenac, of
      total and severe gastrointestinal (GI) adverse events, including dyspepsia,
      abdominal pain, diarrhea, and nausea. The number of patients developing abnormal
      liver function tests (including clinically significant elevation), hemoglobin,
      and creatinine clearance was significantly higher in the oral diclofenac group.
      CONCLUSION: Application of this topical diclofenac solution to the knee of
      patients with OA produced relief of symptoms equivalent to oral diclofenac, with
      minor local skin irritation, but significantly reduced incidence of diclofenac
      related GI complaints and abnormal laboratory values.

PMID- 15468368
TI  - Osteoarthritic mice exhibit enhanced prostaglandin E2 and unchanged calcitonin
      gene-related peptide release in a novel isolated knee joint model.
AB  - OBJECTIVE: Osteoarthritis (OA) is a painful degenerative joint disease. To assess
      joint nociceptor activation indirectly, we used a novel in vitro knee joint
      preparation and determined the release of calcitonin gene-related peptide (CGRP)
      and prostaglandin E2 (PGE2) in osteoarthritic mice. METHODS: We studied STR/1N
      mice, which spontaneously develop OA, along with CD-1 mice as controls and
      C57/Bl6 mice with unilateral collagenase-induced OA and C57/Bl6 control mice. The
      release of CGRP and PGE2 from tibial and femoral joint preparations was
      determined separately in vitro with enzyme immunoassays; we investigated both
      basal release and release induced by stimulation with capsaicin (CAP, 1 microM)
      or bradykinin (BK, 10 microM). RESULTS: Basal PGE2 release from femoral and
      tibial preparations increased by 79% and 97%, respectively, in STR/1N mice
      between 6 and 18 weeks of age when they developed OA, while age-matched CD-1 mice
      exhibited only a weak increase (23%). BK-evoked PGE2 release was significantly
      higher in 18-week-old STR/1N mice (931 +/- 98 pg/ml and 759 +/- 82 pg/ml from
      femoral and tibial preparations, respectively) than in age-matched CD-1 controls
      (236 +/- 38 pg/ml and 246 +/- 34 pg/ml). CAP stimulation induced a significant
      CGRP release, which, however, did not correlate with the temporal development of
      OA in STR/1N mice. Tibial but not femoral joint preparations from mice with
      collagenase-induced OA exhibited a significantly enhanced release upon BK
      stimulation compared to sham controls, while CAP-induced CGRP release did not
      reveal such difference. CONCLUSION: Basal and evoked PGE2 release from knee joint
      preparations rose while osteoarthritic alterations developed, whereas CGRP
      release remained unaltered. The increased PGE2 release may contribute to enhanced
      nociceptor sensitivity underlying chronic OA pain.

PMID- 15468369
TI  - Tenascin-C concentration in synovial fluid correlates with radiographic
      progression of knee osteoarthritis.
AB  - OBJECTIVE: Osteoarthritis (OA) is a major cause of disability and represents the
      most common disease in the aging population. Although the course of the disease
      is generally assessed using standard radiographic images, biochemical markers may
      be employed to detect the disease and determine the degree of severity. We
      developed an enzyme linked immunosorbent assay (ELISA) system using a monoclonal
      antibody specific for the large-splice variants of tenascin-C (TN-C) and examined
      whether TN-C in synovial fluid (SF) is an adequate biochemical marker of OA
      progression. METHODS: SF samples were obtained from knees of 74 patients with OA
      and 16 without OA. Based on the radiographic grading of the OA severity, the
      knees were divided into 3 groups: mild, moderate, and severe OA. Expression of TN
      C splice variants was examined using immunoblotting. TN-C concentrations were
      determined by ELISA. RESULTS: Western blotting showed the presence of large TN-C
      variants in SF from severe OA. TN-C levels were 5-fold higher in OA samples
      compared to subjects without OA (p < 0.0001). TN-C levels were not different
      between control cases and mild OA, but increased significantly in moderate (p =
      0.0244) and severe OA (p < 0.0001). After adjusting TN-C levels for age, body
      mass index, and sex, TN-C levels correlated with radiographic progression of knee
      OA (R2 = 0.404, p < 0.0001). CONCLUSION: TN-C, including the large-variant
      subunits, is a useful biochemical marker for OA progression in the later stages
      of disease.

PMID- 15468370
TI  - Inflammatory markers and physical function among older adults with knee
      osteoarthritis.
AB  - OBJECTIVE: To investigate whether serum concentrations of various inflammatory
      markers are associated with physical function and disease severity among older
      obese adults with knee osteoarthritis (OA). METHODS: Data are from baseline
      assessments in 274 patients with knee OA participating in an exercise and
      nutrition intervention study. The Western Ontario and McMaster University
      Osteoarthritis Index (WOMAC) was used to assess self-reported physical function,
      pain, and stiffness. The presence of disability was assessed, walking speed was
      calculated on the basis of the 6-minute walk test, and knee radiographs
      determined the radiographic severity of OA. Serum concentration of interleukin 6
      (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and
      the soluble receptors IL-6sR, IL-2sR, TNF-sR1 and TNF-sR2 were measured by ELISA.
      RESULTS: In multivariate regression analyses adjusted for age, sex, race, body
      mass index, comorbid conditions, and use of nonsteroid antiinflammatory drugs,
      higher serum levels of TNF-sR1 and TNF-sR2 were significantly associated with
      lower scores on the WOMAC physical function, with more symptoms of pain and
      stiffness, and with more reported physical disability. In addition, higher serum
      levels of TNF-sR1 and TNF-sR2 were significantly associated with slower walking
      speed, and tended to be associated with worse radiographic scores. Higher serum
      levels of IL-6 tended to be associated with slower walking speed, but no
      significant associations were observed for CRP, IL-6sR, or IL-2sR. CONCLUSION:
      Especially high levels of the soluble receptors of TNF-alpha were found to be
      associated with lower physical function, increased OA symptoms, and worse knee
      radiographic scores in older obese adults with knee OA.

PMID- 15468371
TI  - The prevalence of diffuse idiopathic skeletal hyperostosis in Korea.
AB  - OBJECTIVE: To identify the prevalence of diffuse idiopathic skeletal hyperostosis
      (DISH) in a large Asian population group. METHODS: A total of 3595 subjects (1616
      men and 1979 women) over 50 years of age, residing in 2 cities in Korea, were
      included in this study. The mean age of the study population was 64.25 +/- 9.06
      years. We reviewed lateral chest radiographs through Picture Archiving and
      Communication Systems (PACS) and identified DISH according to Resnick's and
      Julkunen's criteria. RESULTS: One hundred and four (2.9%) of the 3595 subjects
      were diagnosed with DISH according to classical Resnick criteria. A slight
      increase in prevalence (4.1%) could be seen using Julkunen's criteria. The
      prevalence of DISH increased with age, except for the 90-99 year age group. Men
      were approximately 7 times more likely to have DISH than women using Resnick's
      criteria. CONCLUSION: DISH is an age-related skeletal disorder whose overall
      prevalence is much lower in Koreans than in other Western populations.
      Interestingly, the prevalence of DISH was 7 times higher in men. We propose that
      ethnic factors are important elements in the prevalence of DISH.

PMID- 15468372
TI  - Interrelations between fibromyalgia, thyroid autoantibodies, and depression.
AB  - OBJECTIVE: To detect and quantify the association between fibromyalgia (FM) and
      thyroid autoimmunity. METHODS: This cross-sectional study comprised 146 women
      with FM and 74 case-controls, all 18 years of age or older. FM was diagnosed
      according to the American College of Rheumatology 1990 classification criteria.
      The Mini-International Neuropsychiatric Interview (MINI) was applied for the
      diagnosis of depression, previously considered as an important confounding
      factor. Thyroid autoimmunity was defined as the occurrence of detectable
      antithyroid peroxidase antibodies and/or antithyroglobulin antibodies by the
      immunometric assay. Cases of diffuse connective tissue diseases and thyroid
      dysfunctions (hypo or hyperthyroidism) were excluded in both groups. RESULTS:
      Univariate analysis detected an association between FM and thyroid autoimmunity
      (odds ratio, OR = 3.87, 95% confidence interval, CI = 1.54-10.13), depression (OR
      = 3.94, 95% CI = 1.97-7.93), and age (OR = 1.04, 95% CI = 1.01-1.07). In the
      final logistic regression model, after adjustment for depression and age, the
      association between FM and thyroid autoimmunity was strengthened (OR = 4.52, 95%
      CI = 1.86-11.0). CONCLUSION: Our results suggest an association between FM and
      thyroid autoimmunity.

PMID- 15468373
TI  - Workshop report: clinical diagnosis and imaging of sacroiliitis, Innsbruck,
      Austria, October 9, 2003.

PMID- 15468374
TI  - Cytokine flexibility of early and differentiated memory T helper cells in
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: It has been suggested that CD45RO+CD27+ T cells represent recently
      activated memory cells, whereas CD45RO+CD27- T cells are activated memory T cells
      in the process of differentiating into effector cells. We investigated (1) CCR7
      and CCR5 expression and (2) modulation of cytokine expression in "early" (CD27+)
      and "differentiated" (CD27-) memory CD4+ T cells from peripheral blood and
      synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA).
      METHODS: SF CD4+CD45RO+CD27+ and CD27- memory T cells from 6 patients with JIA
      were tested by flow cytometry for intracellular interferon-gamma (IFN-gamma) and
      interleukin 4 (IL-4) after in vitro priming with CD3 and CD28 mAb in the presence
      of IL-4, and subsequent culture with IL-2. RESULTS: SF CD4+CD45RO+CD27+ cells
      contained higher proportions of CCR7+ (median 46% vs 23%) and lower proportions
      of CCR5+ (73% vs 90%) cells than paired CD27- T cells. Both CD27+ and CD27-
      memory T helper cells from SF displayed a higher IFN-gamma/IL-4 ratio than their
      peripheral blood counterparts. No significant difference was observed in the
      percentage of IFN-gamma-expressing cells between CD27+ (32%, range 4-47%) and
      CD27- (29.4%, range 5-52%) memory T helper cells from SF. CONCLUSION:
      Irrespective of their differentiation stage, both CD27+ and CD27- SF memory T
      helper cells were found to switch from a proinflammatory to an antiinflammatory
      pattern of cytokine production.

PMID- 15468375
TI  - Prolonged efficacy of etanercept in refractory enthesitis-related arthritis.
AB  - OBJECTIVE: For many children enthesitis-related arthritis (ERA) causes
      substantial morbidity, and conventional treatments frequently offer limited
      efficacy. Tumor necrosis factor-alpha (TNF-alpha) has been found to play a
      central role in the spondyloarthritides. We investigated the longterm efficacy of
      the TNF fusion protein etanercept in the treatment of patients with ERA
      refractory to disease modifying antirheumatic drug (DMARD) therapy. METHODS:
      Eight patients with active, inflammatory ERA were treated in an open-label pilot
      trial of twice weekly subcutaneous injections (dosing range of 25 to 37.5 mg
      twice weekly, 0.2-0.8 mg/kg/dose) of etanercept for 2 years. Outcome measures
      included duration of morning stiffness, active joint count, hemoglobin, and
      erythrocyte sedimentation rate (ESR). Patients were permitted concomitant
      nonsteroidal antiinflammatory drugs (NSAID) and DMARD at stable doses. RESULTS:
      Treatment with etanercept resulted in significant improvement in active joint
      count, hemoglobin, and ESR in all 8 patients within 2 months. Additionally, all
      patients noted increased mobility and overall well being. Improvement in morning
      stiffness did not achieve statistical significance. One patient was lost to
      followup after completing one year of the study. The remaining 7 patients had
      sustained statistically significant efficacy for active joint count, hemoglobin,
      and ESR throughout the entire 2-year trial. All patients tolerated etanercept
      with no side effects. CONCLUSION: Despite limited power, these results indicate
      that etanercept provided a rapid clinical response in our cohort of patients with
      refractory ERA, who achieved sustained efficacy over a 2-year period.

PMID- 15468376
TI  - Polymorphisms in the promoter region of RANTES and the regulatory region of
      monocyte chemoattractant protein-1 among Chinese children with systemic lupus
      erythematosus.
AB  - OBJECTIVE: Chemokines play an important role in the physiology and
      pathophysiology of acute and chronic inflammatory processes. We investigated
      whether chemokines such as RANTES (regulated upon activation, normally T cell
      expressed and secreted) promoter and monocyte chemoattractant protein-1 (MCP-1)
      regulatory polymorphisms were associated with systemic lupus erythematosus (SLE)
      in Chinese children. METHODS: Forty-six patients with SLE and 107 healthy
      children of comparable ages were studied for genotypes with polymerase chain
      reaction-based assays. RESULTS: The frequency and distribution of genotypes of
      the -28(C/G) RANTES gene polymorphism were significantly different between the 2
      groups (p < 0.001), and the RANTES -28G allele was significantly more frequent in
      patients with SLE than in healthy controls (23.9% vs 11%; p = 0.006, OR 2.37, 95%
      CI 1.25-4.28). There was no significant difference in the frequency or in the
      distribution of genotypes of the -2518(A/G) MCP-1 and the -403(G/A) RANTES gene
      polymorphisms between patients and controls (p = 0.32 and p = 0.19,
      respectively). The RANTES -28G allele was also significantly associated with
      higher initial levels of antinuclear antibody, lower levels of C3, and higher
      incidences of central nervous system lupus. CONCLUSION: In the Chinese
      population, children with RANTES -28C/G polymorphisms have increased risk of
      developing SLE. Healthy controls with the C/G or G/G genotype were 2.37 times
      more likely to have SLE compared to those with the C/C genotype.

PMID- 15468377
TI  - Favorable outcome in patients with renal involvement complicating macrophage
      activation syndrome in systemic onset juvenile rheumatoid arthritis.
AB  - Systemic-onset juvenile rheumatoid arthritis (SoJRA) constitutes about 10-20% of
      all JRA. However more than two-thirds of the mortality seen in JRA patients is
      accounted for by SoJRA. Macrophage activation syndrome (MAS), which can also be
      considered as a form of secondary hemophagocytic lymphohistiocytosis, is a major
      cause of morbidity and mortality in children with SoJRA. MAS is characterized by
      persistent high fever, pancytopenia, mild to serious derangements of liver cell
      function, encephalopathy, and disseminated intravascular coagulation. Renal
      involvement in MAS is a rarely recognized feature. In 2 recently reported case
      series of MAS in SoJRA, renal involvement appeared to be associated with poor
      prognosis. We describe 3 children with SoJRA who had renal involvement
      complicating MAS and had a favorable outcome.

PMID- 15468378
TI  - Effective use of the recombinant interleukin 1 receptor antagonist anakinra in
      therapy resistant systemic onset juvenile rheumatoid arthritis.
AB  - Systemic onset juvenile rheumatoid arthritis (SOJRA) is a multisystem disease
      characterized by high fever, rash, arthritis, serositis, splenomegaly, and
      laboratory evidence of systemic inflammation. Anticytokine therapies show promise
      in the treatment of chronic arthritides in children. We describe the use of the
      recombinant interleukin 1 receptor antagonist anakinra in 2 patients with therapy
      resistant SOJRA. Both patients experienced immediate and sustained resolution of
      symptoms and laboratory markers of inflammation, in one case after years of
      treatment with other immunosuppressive therapies.

PMID- 15468379
TI  - Vasculitis associated with the use of leflunomide.
AB  - Vasculitis as a complication of leflunomide therapy in the treatment of
      rheumatoid arthritis has been reported. We describe a case of acute necrotizing
      vasculitis following leflunomide therapy. Characteristics of this case and 4
      cases in the literature suggest that vasculitis may be a rare but serious adverse
      effect of leflunomide therapy.

PMID- 15468380
TI  - Sensory neuropathy revealing necrotizing vasculitis during infliximab therapy for
      rheumatoid arthritis.
AB  - We describe 2 patients with severe erosive rheumatoid arthritis and rheumatoid
      vasculitis, respectively, in whom infliximab therapy was associated with
      peripheral neuropathy due to necrotizing vasculitis in one patient and to
      progression of preexisting mononeuritis multiplex in the other.

PMID- 15468381
TI  - Alpha1-antitrypsin replacement therapy controls fibromyalgia symptoms in 2
      patients with PI ZZ alpha1-antitrypsin deficiency.
AB  - Two Spanish sisters with alpha1-antitrypsin (AAT) deficiency and fibromyalgia
      (FM) started AAT replacement therapy with commercial alpha1-antitrypsin infusions
      in 1992. They both experienced a rapid, progressive, and constant control of
      their FM symptoms during the next 6 years (1992-98). However, in 1998, treatment
      of both patients was affected by the worldwide commercial shortage of AAT
      replacement therapy; replacement therapy infusions were halted for about 4-6
      consecutive months every year for 5 years. As a result, we observed a striking
      recurrence of FM symptoms. Equally striking was the total disappearance of these
      symptoms when AAT replacement therapy infusions were resumed.

PMID- 15468382
TI  - Bone resorption in systemic sclerosis (scleroderma).

PMID- 15468383
TI  - Autoamputation in a patient with cryoglobulinemia.

PMID- 15468384
TI  - Raynaud's phenomenon and serotonin reuptake inhibitors.

PMID- 15468386
TI  - Bibliography. Current world literature. Psychiatry.

PMID- 15468387
TI  - Bibliography. Current world literature. Gastroenterology and nutrition.

PMID- 15468388
TI  - American society of maxillofacial surgeons outcome study: preoperative and
      postoperative neurodevelopmental findings in single-suture craniosynostosis.
AB  - The purpose of this study was to prospectively determine the neurodevelopmental
      effects associated with single-suture, nonsyndromic craniosynostosis before and
      after surgery. Children diagnosed with single-suture craniosynostosis were
      evaluated by a psychologist using the Bayley Scales of Infant Development-Second
      Edition (BSID-II) within 2 months before and again 1 year after surgical
      correction. The BSID-II is a widely used measure of infant cognitive and motor
      development. The scale consists of three parts, the Mental Developmental Index
      (MDI), the Psychomotor Developmental Index (PDI), and the Behavior Rating Scale.
      The MDI and PDI yield age-standard scores (mean, 100; SD, 16). The children
      ranged in age from 2.5 to 10 months at the time of the craniofacial
      reconstruction (average age, 5.9 months). Metopic synostosis was diagnosed in 23
      percent, sagittal synostosis in 45 percent, and unilateral coronal synostosis in
      32 percent of patients. Twenty-two patients were evaluated preoperatively, of
      whom 15 patients were evaluated postoperatively. Mean baseline BSID-II scores
      revealed a mild delay in mental and motor scores (MDI, 82.3; PDI, 79.5). Mean
      postoperative BSID-II scores still revealed a mild delay in mental scores but
      significantly improved motor scores (MDI, 79.3; PDI, 89.3). Of the 15 children,
      four (27 percent) had BSID-II evaluations that were in the average range for all
      scales and nine infants (60 percent) had at least one MDI or PDI score in the
      significantly delayed range (<70). Among children with single-suture nonsyndromic
      craniosynostosis, mean Bayley scores indicated mild baseline deficits in both
      mental and motor scores. After surgical treatment, improvement was seen in the
      motor scale. It appears from this sample that neurodevelopmental abnormalities
      may be present in children with single-suture synostosis, and some may persist at
      1 year of follow-up.

PMID- 15468389
TI  - Resorbable PLLA-PGA plate and screw fixation in pediatric craniofacial surgery:
      clinical experience in 1883 patients.
AB  - The need to provide rigid bony fixation in the surgical treatment of craniofacial
      deformities has inspired an on-going evolution of surgical innovations and
      implants. Because of the young age of many treated craniosynostosis patients and
      the unique pattern of cranial vault growth, the extensive implantation of metal
      devices is potentially problematic. The use of resorbable plate and screw devices
      offers all of the benefits of rigid fixation without many of their potential
      risks. Since the introduction of resorbable plate and screw devices in 1996, tens
      of thousands of craniofacial patients have received implants, but long-term
      results from a large series have yet to be reported. A combined prospective and
      retrospective analysis was done on 1883 craniosynostosis patients under 2 years
      of age treated by 12 surgeons from seven different geographic locations over a 5
      year period who used the same type of resorbable bone fixation devices (poly-L
      lacticpolyglycolic copolymer). Specifically, the incidence of postoperative
      infection, fixation device failure, occurrence of delayed foreign-body reactions,
      and the need for reoperation resulting from device-related problems were
      determined. Technical difficulties and trends in device use were also noted. From
      this series, significant infectious complications occurred in 0.2 percent, device
      instability primarily resulting from postoperative trauma occurred in 0.3
      percent, and self-limiting local foreign-body reactions occurred in 0.7 percent
      of the treated patients. The overall reoperation rate attributable to
      identifiable device-related problems was 0.3 percent. Improved bony stability was
      gained by using the longest plate geometries/configurations possible and bone
      grafting any significant gaps across plated areas that were structurally
      important. The specific types of plates and screws used evolved over the study
      period from simple plates, meshes, and threaded screws to application-specific
      plates and threadless push screws whose use varied among the involved surgeons.
      This report documents the safety and long-term value of the use of resorbable
      (LactoSorb) plate and screw fixation in pediatric craniofacial surgery in the
      infant and young child. Device-related complications requiring reoperation
      occurred in less than 0.5 percent of the implanted patients, which is less
      frequent than is reported for metallic bone fixation. Resorbable bone fixation
      for the rapidly growing cranial vault has fewer potential complications than the
      traditional use of metal plates, screws, and wires.

PMID- 15468390
TI  - The progressive changes of nasal symmetry and growth after nasoalveolar molding:
      a three-year follow-up study.
AB  - The purpose of this study was to assess the progressive changes of nasal
      symmetry, growth, and relapse after presurgical nasoalveolar molding and primary
      cheiloplasty in unilateral complete cleft lip/palate infants. Twenty-five
      consecutive complete unilateral cleft lip/palate infants were included. All the
      infants underwent nasoalveolar molding before primary cheiloplasty. Standard 1:1
      ratio basilar photographs were taken before and after nasoalveolar molding, 1
      week after cheiloplasty, and yearly for 3 years. Linear measurements were made
      directly on the photographs. The results of this study revealed that the nasal
      asymmetry was significantly improved after nasoalveolar molding and was further
      corrected to symmetry after primary cheiloplasty. After the primary cheiloplasty,
      the nasal asymmetry significantly relapsed in the first year postoperatively and
      then remained stable and well afterward. The relapse was the result of a
      significant differential growth between the cleft and noncleft sides in the first
      year postoperatively. To compensate for relapse and differential growth, the
      authors recommend (1) narrowing down the alveolar cleft as well as possible by
      nasoalveolar molding, (2) overcorrecting the nasal vertical dimension surgically,
      and (3) maintaining the surgical results using a nasal conformer.

PMID- 15468391
TI  - Dynamic reconstruction of eye closure by muscle transposition or functional
      muscle transplantation in facial palsy.
AB  - For patients with facial palsy, lagophthalmus is often a more serious problem
      than the inability to smile. Dynamic reconstruction of eye closure by muscle
      transposition or by free functional muscle transplantation offers a good solution
      for regaining near-normal eye protection without the need for implants. This is
      the first quantitative study of three-dimensional preoperative and postoperative
      lid movements in patients treated for facial paralysis. Between February of 1998
      and April of 2002, 44 patients were treated for facial palsy, including
      reconstruction of eye closure. Temporalis muscle transposition to the eye was
      used in 34 cases, and a regionally differentiated part of a free gracilis muscle
      transplant after double cross-face nerve grafting was used in 10 cases. Patients'
      facial movements were documented by a three-dimensional video analysis system
      preoperatively and 6, 12, 18, and 24 months postoperatively. For this comparative
      study, only the data of patients with preoperative and 12-month postoperative
      measurements were included. In the 27 patients with a final result after
      temporalis muscle transposition for eye closure, the distance between the upper
      and lower eyelid points during eye closing (as for sleep) was reduced from 10.33
      +/- 2.43 mm (mean +/- SD) preoperatively to 5.84 +/- 4.34 mm postoperatively on
      the paralyzed side, compared with 0.0 +/- 0.0 mm preoperatively and
      postoperatively on the contralateral healthy side. In the resting position,
      preoperative values for the paralyzed side changed from 15.11 +/- 1.92 mm
      preoperatively to 13.46 +/- 1.94 mm postoperatively, compared with 12.17 +/- 2.02
      mm preoperatively and 12.05 +/- 1.95 mm postoperatively on the healthy side. In
      the nine patients with a final result after surgery using a part of the free
      gracilis muscle transplant reinnervated by a zygomatic branch of the
      contralateral healthy side through a cross-face nerve graft, eyelid closure
      changed from 10.21 +/- 2.72 mm to 1.68 +/- 1.35 mm, compared with 13.70 +/- 1.56
      mm to 6.63 +/- 1.51 mm preoperatively. The average closure for the healthy side
      was from 11.20 +/- 3.11 mm to 0.0 +/- 0.0 mm preoperatively and from 12.70 +/-
      1.95 mm to 0.0 +/- 0.0 mm postoperatively. In three cases, the resting tonus of
      the part of the gracilis muscle transplant around the eye had increased to an
      extent that muscle weakening became necessary. Temporalis muscle transposition
      and free functional muscle transplantation for reanimation of the eye and mouth
      at the same time are reliable methods for reconstructing eye closure, with
      clinically adequate results. Detailed analysis of the resulting facial movements
      led to an important improvement of the authors' operative techniques within the
      last few years. Thus, the number of secondary operative corrections could be
      significantly reduced. These qualitative and quantitative studies of the
      reconstructed lid movements by three-dimensional video analysis support the
      authors' clinical concept of temporalis muscle transposition being the first
      choice method in adult patients with facial palsy. In children, free muscle
      transplantation is preferred for eye closure, so as not to interfere with the
      growth of the face by transposition of a masticatory muscle. In addition, a
      higher degree of central plasticity in children might be expected.

PMID- 15468392
TI  - A rational approach to nasal reconstruction in leprosy.
AB  - Destruction of the nasal septum and nasal bones by Mycobacterium leprae and
      subsequent infection is still seen regularly in leprosy endemic areas. The social
      stigma associated with this deformity is significant. Many different procedures
      have been developed to reconstruct the nose. Patients operated on at Anandaban
      Hospital and the Green Pastures Hospital and Rehabilitation Center between 1986
      and 2001 were reviewed. There were 48 patients with an average age of 47 years.
      Five deformities were mild, 22 were moderate, 13 were severe, and eight were not
      graded. Bone grafting with nasolabial skin flaps was performed in 14 cases, bone
      grafting alone was performed in 10 cases, flaps alone were performed in seven
      cases, and cartilage grafting was performed in 10 cases. In three patients, a
      prosthesis was inserted, and in three patients a gull-wing forehead flap was
      performed. Overall, excellent or good cosmetic results were obtained in 83
      percent of cases. Grafting with conchal cartilage was associated with the best
      cosmetic results and had minimal complications. Bone grafting with or without
      nasolabial flaps was associated with a 50 percent complication rate of infection
      or graft resorption. In mild to moderate deformities, cartilage grafting is
      recommended; for more severe deformities, bone grafting with bony fixation and
      skin flaps is recommended. Perioperative antibiotics must be used, and these
      procedures should be performed by an experienced surgeon. In very severe cases
      with skin deficiency, reconstruction with a forehead flap gives good results.

PMID- 15468393
TI  - Bilobed fasciocutaneous flap for reconstruction of the posterior neck after
      necrotizing fasciitis.
AB  - Necrotizing fasciitis is an aggressive, deep-seated infection of the fascia and
      subcutaneous fat with necrosis of overlying skin. Eleven cases of necrotizing
      fasciitis of the posterior neck are reviewed to demonstrate the advantage of
      using a bilobed fasciocutaneous flap for repair following surgical debridement.
      Nine men and two women aged 40 to 65 years (mean age, 54.8 years) presented for
      reconstruction from April of 1999 to March of 2003. The blood supply of the
      bilobed fasciocutaneous flap originates from a constant row of musculocutaneous
      perforators of posterior intercostal arteries. The technique enabled regional
      reconstruction, conserved tissues, and provided satisfactory aesthetic results.

PMID- 15468394
TI  - Breast-feeding after vertical mammaplasty with medial pedicle.
AB  - A retrospective study was performed in which the breast-feeding success of women
      of childbearing age (15 to 40 years) with macromastia but no prior breast surgery
      was compared with that of women of similar age who had undergone medial
      pedicle/vertical pattern reduction mammaplasty. All women completed a self
      administered questionnaire that provided information on their breast-feeding
      success. The control group consisted of 149 women with macromastia (mean age, 27
      years) who had been evaluated for possible breast reduction surgery and who had
      children before their consultation. The study group consisted of 58 women (mean
      age, 29 years) who had children after their vertical mammaplasty. The mean weight
      of breast tissue removed was 610 g per breast. None of the patients had absent
      nipple sensation. A period of 2 weeks or more was chosen as the defining duration
      of a successful breast-feeding attempt. Those individuals judged able to breast
      feed were further classified on the basis of having breast-fed exclusively or
      with supplementation. The results demonstrated that, of the women who attempted
      to breast-feed, 61 percent in the control group and 65 percent in the study group
      were successful, with no significant difference between the groups (p > 0.05).
      The breakdown of the successful groups indicated that 36 percent in the control
      group and 38 percent in the study group supplemented their breast-feeding with
      formula. The groups were not significantly different (p > 0.05). In conclusion,
      this study found no significant difference in the rate of breast-feeding success
      between women who had medial pedicle/vertical pattern reduction mammaplasty and
      women who had no prior breast surgery.

PMID- 15468395
TI  - Efficacy of the pain pump catheter in immediate autologous breast reconstruction.
AB  - The purpose of the investigation was to evaluate the efficacy of a slow
      bupivacaine infusion at postoperative surgical sites in immediate breast
      reconstruction patients. This prospective study included 16 patients who
      underwent autologous breast reconstruction with a latissimus dorsi pedicled flap
      immediately after mastectomy. A two-site infusion kit with dual split-flow
      catheters was secured at the operative sites before skin closure. A spring-loaded
      disposable pump then infused 0.25% bupivacaine at a rate of 2.08 cc per catheter
      per hour for 48 continuous hours. Patient pain levels, nausea/emesis, and oral
      and intravenous narcotic use were then recorded at 12-hour intervals. Medication
      use was converted to pain units for results comparison (one pain unit was defined
      as the equivalent of 10 mg of intravenous morphine). A retrospective control
      group comprised 16 consecutive patients from December of 1999 to October of 2002
      who underwent the same surgery by the same surgeon using oral and intravenous
      pain medications. The experimental group demonstrated a more than fivefold
      decrease in the use of oral and intravenous pain medications compared with the
      historical controls (6.7 versus 1.7 pain units) (p < 0.001). The overall pain
      experienced by the catheter patients was nearly twofold less than the pain
      experienced by those without the catheter (1.8 versus 3.4 on the visual analog
      pain scale) (p < 0.017). Twenty-eight percent of the experimental group
      experienced nausea/emesis compared with 61 percent in the control group. No
      complications occurred with the use of the pain pump catheter. A 48-hour infusion
      of 0.25% bupivacaine significantly decreases the need for postoperative narcotics
      and the over-all pain experience in immediate breast reconstruction patients.
      This effective form of pain control may alleviate patient concerns of
      postoperative pain and may safely downstage many plastic surgery procedures, such
      as immediate breast reconstruction, and many cosmetic procedures to same-day
      status when the primary indication for admission is pain management.

PMID- 15468396
TI  - Triple coverage of ischial ulcers with adipofascial turnover and fasciocutaneous
      flaps.
AB  - Despite a wide variety of flap options, ischial ulcers remain the most difficult
      pressure ulcers to treat. This article describes the authors' successful surgical
      procedure for coverage of ischial ulcers using adipofascial turnover flaps
      combined with a local fasciocutaneous flap. After debridement, the adipofascial
      flaps are harvested both cephalad and caudal to the defect. The flaps are then
      turned over to cover the exposed bone in a manner so as to overlap the two flaps.
      A local fasciocutaneous flap (Limberg flap) is applied to the raw surface of the
      turnover flaps. Twenty-two patients with ischial ulcers were treated using this
      surgical procedure. Overall, 86.4 percent of the flaps (19 of 22) healed
      primarily. Triple coverage with the combination of double adipofascial turnover
      flaps and a local fasciocutaneous flap allows for an easily performed and
      minimally invasive procedure, preservation of future flap options, and a soft
      tissue supply sufficient for covering the prominence and bony prominence and
      filling dead space. This technique provides successful soft-tissue reconstruction
      for minor to moderate-size ischial pressure ulcers.

PMID- 15468397
TI  - Distal perforator-based fasciocutaneous V-Y flap for treatment of sacral pressure
      ulcers.
AB  - Although the gluteal V-Y advancement flap has been recognized as the most
      reliable method for management of sacral pressure ulcers, its limited mobility
      has been a challenging problem. The authors present a new modification of the V-Y
      advancement flap to overcome the problem. After debridement, a large triangle is
      designed to create a V-Yadvancement flap on the unilateral buttock and the medial
      half is elevated as a fasciocutaneous flap, preserving the distal perforators in
      the muscular attachment. Then an arc-shaped incision is made in the gluteus
      maximus muscle along with the lateral edge of the triangular flap. The split
      muscle is elevated at a depth above the deeper fascia until sufficient
      advancement of the flap is obtained. This full-thickness elevation of the gluteus
      maximus muscle from the distal (lateral) side avoids the impairment of
      perforators or their mother vessels and achieves great advancement. Thirty-one
      patients with sacral pressure defects larger than 8 cm in diameter were treated
      using this surgical procedure. Overall, 93.5 percent of the flaps (29 of 31)
      healed primarily. The largest defect that was closed with a unilateral flap was
      16 cm in diameter. The present technique accomplishes remarkable excursion of the
      unilateral V-Y fasciocutaneous flap, with high flap reliability and preservation
      of the contralateral buttock as well as gluteus maximus muscle function.

PMID- 15468398
TI  - Free-style free flaps.
AB  - Free-tissue transfer has become the accepted standard for reconstruction of
      complex defects. With the growth of this field, anatomic studies and clinical
      work have added many flaps to the armamentarium of the microvascular surgeon.
      Further advancements and experience with techniques of perforator flap surgery
      have allowed for the harvest of flaps in a free-style manner, where a flap is
      harvested based only on the preoperative knowledge of Doppler signals present in
      a specific region. Between June of 2002 and September of 2003, 13 free-style free
      flaps were harvested from the region of the thigh. All patients presented with an
      oral or pharyngeal cancer and underwent resection and immediate reconstruction of
      these flaps. All flaps were cutaneous and were harvested in a suprafascial plane.
      The average size of the flaps was 108 cm2 (range, 36 to 187 cm2), and the average
      length of the vascular pedicle was 10 cm (range, 9 to 12 cm). All flaps were
      successful in achieving wound coverage and functional outcomes without any
      vascular compromise necessitating re-exploration. Free-style free flaps have
      become a clinical reality. The concepts and techniques used to harvest a free
      style free flap will aid in dealing with anatomic variations that are encountered
      during conventional flap harvest. Future trends in flap selection will focus
      mainly on choosing tissue with appropriate texture, thickness, and pliability to
      match requirements at the recipient site while minimizing donor-site morbidity.

PMID- 15468399
TI  - A prospective, blinded, randomized, controlled clinical trial of topical negative
      pressure use in skin grafting.
AB  - Topical negative pressure has been demonstrated to improve graft take in a number
      of noncomparative studies. This study aimed to assess whether split-thickness
      skin graft take is improved qualitatively or quantitatively with topical negative
      pressure therapy compared with standard bolster dressings. A blinded,
      prospective, randomized trial was conducted of 22 adult inpatients of Liverpool
      Hospital between July of 2001 and July of 2002 who had wounds requiring skin
      grafting. After grafting, each wound half was randomized to receive either a
      standard bolster dressing or a topical negative pressure dressing. Skin graft
      assessment was performed at 2 weeks by a single observer blinded to the
      randomization. Two patients were lost to follow-up and were excluded from the
      study. There were 20 patients (12 men and eightwomen) in the study group. The
      median patient age was 64 years (range, 27 to 88 years), and the mean wound size
      was 128 cm2 (range, 35 to 450 cm2). The wound exposed subcutaneous fat in eight
      patients, muscle in six patients, paratenon in four patients, and deep fascia in
      two patients. At 2 weeks, wounds that received a topical negative pressure
      dressing had a greater degree of epithelialization in six cases (30 percent), the
      same degree of epithelialization in nine cases (45 percent), and less
      epithelialization in five cases (25 percent) compared with their respective
      control wounds. Graft quality following topical negative pressure therapy was
      subjectively determined to be better in 10 cases (50 percent), equivalent in
      seven cases (35 percent), and worse in three cases (15 percent). Although the
      quantitative graft take was not significant, the qualitative graft take was found
      to be significantly better with the use of topical negative pressure therapy (p <
      0.05). Topical negative pressure significantly improved the qualitative
      appearance of split-thickness skin grafts as compared with standard bolster
      dressings.

PMID- 15468400
TI  - Plastic surgeon's life: marvelous for mind, exhausting for body.
AB  - Surgery is accepted as one of the most demanding professions that create both
      physical and mental strain on the performers. Therefore, the authors aimed to
      elucidate the mental burden of surgeons, which is dedicated to operative stress.
      They also tested the hypotheses that participating in surgery creates mental
      stress on surgeons that leads to cardiovascular changes, and that this stress is
      more pronounced for actual operators than for first assistants. The method chosen
      for this purpose was an analysis of heart rate variability. Twelve surgeons (five
      plastic surgery staff and seven plastic surgery residents) were monitored by a
      digital ambulatory Holter recorder on at least two occasions. Half of the
      recordings were carried out on operating days and the other half on office days.
      Heart rate variability indices (low frequency, high frequency, high frequency/low
      frequency ratio, and heart rate) were analyzed from those recordings using
      computerized research tool software. The heart rate variability indices of the
      operators showed statistically significant differences between operating days and
      office hours in favor of an increased sympathetic and decreased parasympathetic
      activity for the former. For first assistants, three of the parameters, with the
      exception of heart rate, changed in favor of a sympathetic predominance over
      parasympathetic activity; these changes were also statistically significant.
      These results showed a sympathetic hyperactivity for both operators and first
      assistants during the operations. When the sympathovagal balance of the actual
      operators was compared with that of assistants, the former group showed a more
      pronounced sympathetic arousal. This difference is accepted as a proof for the
      mental stress of the surgery being the main factor responsible for the
      sympathetic hyperactivity that we detected during the operations. Surgeons
      continuously face a unique mental strain that other professions rarely bring
      forth, and these psychological stressors are associated with alterations in
      cardiac autonomic control that may contribute to the development of cardiac
      disease. Prolonged sympathetic hyperactivity could anticipate cardiac discomfort
      in more experienced surgeons with marginal cardiac reserve. Such cardiac diseases
      would be reconsidered as occupation-related illnesses, which might be reimbursed
      to the physician. In addition, the legal responsibility of surgeons concerning
      their unfavorable results might be assessed with more understanding with a
      realization of their undue working conditions.

PMID- 15468402
TI  - Spontaneous thrombosis of the radial artery at the wrist level.

PMID- 15468401
TI  - Biocompatibility and tissue interactions of a new filler material for medical
      use.
AB  - Filler materials for medical use present limits, such as the induction of chronic
      inflammation and fibrosis. In the search for synthetic materials with improved
      biocompatible properties, a new polyacrylamide hydrogel, Aquamid (Contura SA,
      Montreux, Switzerland), has been investigated in preclinical systems. In cell
      cultures (endothelial cells and fibroblast), no or only transient biological
      effects were associated with 10% Aquamid exposure. The Aquamid-host interactions
      were examined in mice (10 mice per group) implanted subcutaneously or in the
      mammary fat pad with a very large volume (1.5 ml) of the material. Blood
      analysis, performed after 15 and 94 days (five mice per time for each group) to
      detect acute or late manifestations of toxicity, did not reveal relevant
      abnormalities in either group of Aquamid-bearing mice compared with control mice,
      except for a transient thrombocytopenia and a mild leukocytosis. Histological
      analysis of the pellet showed the presence of a thin, poorly vascularized cyst
      wall in implants. Only mild mesenchymal reparative and inflammatory processes
      were observed, even at longer observation times (more than 400 days). No
      alterations in any organ were detected. Despite the large volume implanted
      (approximately 5 percent of mouse body weight), the Aquamid pellet maintained its
      original size and shape without spreading or sticking to surrounding tissues. In
      conclusion, the study indicated a good tolerability of the new biopolymer in
      preclinical systems. The clinical utility of this new compound, if confirmed by
      clinical randomized trials showing its atoxic properties, could be in the field
      of aesthetic plastic surgery as a filler material for body contouring and in
      reconstructive surgery and above all in cancer patients to restore surgical
      defects.

PMID- 15468403
TI  - A Web site service for plastic surgeons: new ideas for patients' records.

PMID- 15468404
TI  - Breast reconstruction with postmastectomy radiation therapy: current issues.
AB  - Two recent trials have demonstrated superior locoregional control, disease-free
      survival, and overall survival in node-positive breast cancer patients with the
      addition of postmastectomy radiation therapy to mastectomy and chemotherapy.
      Based on these results, there has been an increased use of postmastectomy in
      patients with early-stage breast cancer. The inability to determine which
      patients will require postmastectomy radiation therapy has increased the
      complexity of planning for immediate breast reconstruction. There are two
      potential problems with performing an immediate breast reconstruction in a
      patient who will require postmastectomy radiation therapy. One problem is that
      postmastectomy radiation therapy can adversely affect the aesthetic outcome of an
      immediate breast reconstruction. Several studies have evaluated the outcomes of
      breast reconstructions that were performed before radiation therapy and have
      revealed a high incidence of complications and poor aesthetic outcomes.
      Furthermore, these studies have found that often an additional flap is required
      to restore breast shape and symmetry. The other potential problem is that an
      immediate breast reconstruction can interfere with the delivery of postmastectomy
      radiation therapy. During planning for immediate breast reconstruction, it is
      imperative to carefully review the stage of disease and the likelihood the
      patient will require postmastectomy radiation therapy. Unfortunately, the ability
      to detect and predict the presence or extent of axillary lymph node involvement
      is limited, and the need for postmastectomy radiation therapy is usually not
      known until after mastectomy. In all cases of decision making regarding possible
      postoperative radiation therapy and whether or not to perform immediate breast
      reconstruction, the situation should be discussed at a multidisciplinary
      conference or addressed among the various medical, surgical, and radiation teams,
      with active participation by the patient. Immediate breast reconstruction
      probably should be avoided in patients known to require postmastectomy radiation
      therapy and delayed until it is certain the therapy will be needed in patients
      who may require the therapy.

PMID- 15468405
TI  - Philadelphia's legacy of the revolution: American surgical art.

PMID- 15468406
TI  - Artecoll: a long-lasting injectable wrinkle filler material: Report of a
      controlled, randomized, multicenter clinical trial of 251 subjects.
AB  - Artecoll, an injectable wrinkle filler composed of polymethylmethacrylate
      microspheres and bovine collagen, is widely available outside the United States.
      For domestic availability, a multicenter Investigational Device Exemption study
      was required by the U.S. Food and Drug Administration. This study consisted of
      251 subjects at eight centers who received injections of Artecoll or the
      currently approved collagen dermal filler (control) in 1334 wrinkles of the
      glabella, nasolabial fold, radial upper lip lines, and corner-of-the-mouth lines.
      The treatments were randomized, and follow-up safety, efficacy, investigator
      success rating, and subject satisfaction rating data were collected at 1, 3, and
      6 months. The safety data, measured as adverse events and immunoglobulin G serum
      levels, were low and similar for both groups. The efficacy data, measured by
      masked observers using a photographic facial fold assessment scale, demonstrated
      a combined significant improvement with Artecoll compared with collagen at 6
      months (p < 0.001). At 6 months, the investigator success ratings and the subject
      satisfaction ratings for each of the four injections sites were superior for
      Artecoll (p < 0.001). In the Artecoll group, 12-month follow-up was obtained for
      111 subjects (86.7 percent) and showed persistence of significant augmentation.
      Artecoll had fewer adverse events reported throughout the 12-month safety study
      period than the control group did in 6 months, although the difference was not
      statistically significant.

PMID- 15468407
TI  - Improving periorbital appearance in the "morphologically prone".
AB  - Patients with prominent eyes are predisposed to lower lid descent and rounding of
      the palpebral fissure. This deformity may be exaggerated and symptomatic after
      conventional lower blepharoplasty. Normalization of the periorbital appearance in
      "morphologically prone" patients involves three basic maneuvers. Augmenting the
      projection of the infraorbital rim with an alloplastic implant effectively
      changes the skeletal morphology, thereby providing support for the lower lid and
      midface soft tissues. Subperiosteal freeing and elevation of the lower lid and
      midface recruits soft tissues and allows lower lid repositioning. Lateral
      canthopexy restores palpebral fissure shape and provides additional lid support.
      The technique can be adapted for morphologically prone patients who are first
      seeking improvement in their periorbital appearance or for those whose lid
      malposition and round eye appearance have been exaggerated by previous lower
      blepharoplasty. This surgery has been effective treatment for 13 morphologically
      prone patients operated on over a 4-year period.

PMID- 15468408
TI  - Effect of face lift on earlobe ptosis and pseudoptosis.
AB  - The authors have previously described a classification system for earlobe ptosis
      and established criteria for earlobe pseudoptosis. Earlobe heights were
      characterized on the basis of anatomic landmarks, including the intertragal
      notch, the otobasion inferius (the most caudal anterior attachment of the earlobe
      to the cheek skin), and the subaurale (the most caudal extension of the earlobe
      free margin). The classification system was derived from earlobe height
      preferences as determined by a survey of North American Caucasians and identified
      the ideal free caudal segment (otobasion inferius to subaurale distance)
      measuring 1 to 5 mm (grade I ptosis). Also, earlobe pseudoptosis was defined by
      an attached cephalic segment (intertragal notch to otobasion inferius distance)
      measuring greater than 15 mm. In this study, the authors evaluated the effects of
      standard face lift surgery on earlobe ptosis and pseudoptosis by comparing the
      preoperative and postoperative earlobe height measurements from life-size
      photographs of 44 patients who underwent rhytidectomy performed by the senior
      author. The postoperative attached cephalic segment (intertragal notch to
      otobasion inferius distance, 12.22 +/- 0.364 mm) increased over its preoperative
      attached cephalic segment (intertragal notch to otobasion inferius distance,
      11.10 +/- 0.406 mm) (p = 0.041). The postoperative free caudal segment (otobasion
      inferius to subaurale distance, 6.32 +/- 0.438 mm) demonstrated only a trend
      toward decreased heights when compared with the preoperative free caudal segment
      (otobasion inferius to subaurale distance, 7.15 +/- 0.489 mm) (p = 0.210). The
      incidence of pseudoptosis, defined by an attached segment (intertragal notch to
      otobasion inferius distance) greater than 15 mm, increased from 12.3 percent of
      preoperative patient earlobes to 17.3 percent of postoperative patient earlobes.
      An ideal free caudal segment (otobasion inferius to subaurale distance), defined
      by a range of 1 to 5 mm, was observed in only 37.0 percent of postoperative
      earlobes versus 22.2 percent of preoperative earlobes. Significant increases in
      the attached cephalic segments (intertragal notch to otobasion inferius distance)
      following rhytidectomies correlated with increased incidence of earlobe
      pseudoptosis, as observed in 17.3 percent of postoperative patient earlobes.
      Because the free caudal segment was negligibly affected by rhytidectomy, a
      majority of earlobes (63.0 percent) demonstrated persistent nonoptimal free
      caudal segment heights (otobasion inferius to subaurale distance > 5 mm). Earlobe
      height changes can result from either age-related lobule ptosis (increase in free
      caudal segment) as previously described or in patients undergoing rhytidectomy
      (increase in attached cephalic segment). Therefore, ideal lobule distances along
      with the effects of aging and rhytidectomy surgery on the lobule should be
      discussed with patients who are seeking a more youthful facial appearance, so
      that the aging ear may be addressed concurrently with the aging face.

PMID- 15468409
TI  - Abdominal dermolipectomy in an abdomen with pre-existing scars: a different
      concept.
AB  - Although abdominal dermolipectomy is a frequently performed procedure, few
      publications have reported on the safety of the procedure in the scarred abdomen.
      The aim of this study was to stress the possibility of performing a natural
      looking abdominoplasty with no complication such as skin necrosis or liponecrosis
      in the presence of abdominal scars and to clarify that the scarred abdomen is not
      a great limitation for full abdominoplasty as reported in the literature. Seventy
      six abdominoplasties were performed on scarred patients from July of 1997 to June
      of 2003. Twenty-five patients had oblique subcostal scars, six patients had
      median supraumbilical scars, three patients had median infraumbilical scars, 10
      patients had appendectomy scars, nine patients had paramedian supraumbilical
      scars, eight patients had paramedian infraumbilical scars, seven patients had
      long transverse scars of repaired ventral hernias, and eight patients had
      multiple small scars after laparoscopy. In addition, there were concomitant
      transverse cesarean delivery scars in 40 patients. All patients underwent full
      abdominoplasties, plication of the musculoaponeurotic system, and liposuction
      assistance if required (45 patients). Of 76 subjects, three patients had very
      limited liponecrosis at the watershed area. Eleven patients (14.5 percent) were
      morbidly obese and heavy smokers. In comparisons of postabdominoplasty
      complications, such as liponecrosis, wound infection, and dehiscence with and
      without liposuction in scarred abdomen, no significant differences were found.
      Secondary revision was more common among abdominoplasties without liposuction
      [seven of 45 (15.6 percent) versus 12 of 31 (38.7 percent); p = 0.02]. In
      conclusion, there is no limitation or contraindication for abdominal
      dermolipectomy with or without liposuction assistance on the previously scarred
      abdomen as long as the vascular zones of the abdomen are respected. The abdominal
      wall dissection is limited to allow only the plication of the musculoaponeurotic
      system, and aggressive liposuction is avoided.

PMID- 15468410
TI  - Tales of greed.

PMID- 15468411
TI  - Infectious and respiratory hazards of nail sculpture.

PMID- 15468412
TI  - Use of the scalp vein infusion set for irrigation in infections of the hand.

PMID- 15468413
TI  - Use of tracheal tube in isolated fractures of the zygomatic arch.

PMID- 15468414
TI  - Castroviejo caliper: a useful tool in plastic surgery.

PMID- 15468415
TI  - Effect of cerebrospinal fluid on resorbable plate absorption.

PMID- 15468416
TI  - Dextran-related complications in head and neck microsurgery: do the benefits
      outweigh the risks?

PMID- 15468417
TI  - The golden ratio and proportions of beauty.

PMID- 15468418
TI  - Nipple or areolar reduction with simultaneous breast augmentation.

PMID- 15468419
TI  - An unusual complication following free-tissue transfer: pulse rate perception.

PMID- 15468420
TI  - Pathological tissue expansion.

PMID- 15468421
TI  - Meralgia paresthetica in a policeman: the belt or the gun.

PMID- 15468422
TI  - The co-existence of Treacher Collins syndrome and Klinefelter syndrome.

PMID- 15468423
TI  - Management of traumatic complete laceration of the median artery at the carpal
      tunnel: repair or ligate?

PMID- 15468424
TI  - Chest wall reconstruction with acellular dermal matrix (AlloDerm) and a
      latissimus muscle flap.

PMID- 15468425
TI  - Maximizing the use of the abdominoplasty incision.

PMID- 15468426
TI  - Inferior epigastric artery as autogenous arterial graft.

PMID- 15468427
TI  - The island rotation flap: a better alternative for nasal tip repair.

PMID- 15468429
TI  - Hepatitis C in the setting of HIV.

PMID- 15468428
TI  - Cadaveric fascia temporalis graft for pulley reconstruction.

PMID- 15468430
TI  - Designing effective HIV prevention strategies for female street sex workers.

PMID- 15468431
TI  - Hepatitis C and B-cell lymphoma.
AB  - Hepatitis C virus (HCV) infection is a major public health problem worldwide.
      HCV, a lymphotropic and hepatotropic virus, is clearly associated with cirrhosis,
      end-stage liver disease, autoimmune phenomena, hepatocellular carcinoma, and
      essential mixed cryoglobulinemia. Recently, there have been increasing reports of
      B-cell lymphomas in patients with HCV infection, and epidemiologic data from
      several sources have demonstrated high rates of HCV seroprevalence in patients
      with B-cell malignancies. This review describes a case report of a patient with
      HCV and chronic lymphocytic leukemia, followed by a summary of the literature on
      this rapidly evolving area.

PMID- 15468432
TI  - Sexual transmission of hepatitis C virus and prevention with intramuscular
      immunoglobulin.
AB  - The sexual transmission of hepatitis C virus (HCV) has long been debated. The
      prevalence of infected at-risk partners varies from 0% to 30%. In a prospective
      study, the risk of infection was quantified in steady heterosexual partners and
      the prophylactic effect of normal human polyvalent immune serum globulin (ISG)
      was evaluated. A total of 899 at-risk partners of HCV-infected patients were
      enrolled in a single-blind randomized controlled trial and assigned to receive
      every 2 month 4 mL of intramuscular ISG from unscreened donors (450 partners) or
      placebo (499 partners). Seven partners developed acute HCV infection (increased
      aminotransferase levels and appearance of HCV-RNA): six of the placebo group
      (incidence density [ID] 12.00/1,000 person year; 95% confidence interval [CI] 3.0
      to 21.61), and only one of the ISG-treated group (ID 1.98/1,000 person year; 95%
      CI 0 to 5.86). The risk of infection was significantly higher in controls versus
      treated individuals (p = 0.03). Six couples had genotype 1b (85%), and one couple
      had genotype 1a; HCV sequence homology strongly supported sexual transmission.
      Our trial demonstrates that HCV infection can be sexually transmitted and
      quantifies the risk of sexual transmission: for every year of at-risk sexual
      relationship, almost 1% of the partners became infected. Intramuscular ISG is
      safe and well tolerated. Unlike ISG from screened donors, ISG from donors
      unscreened for anti-HCV contains high titers of anti-gpE1/gpE2 neutralizing
      antibodies and high neutralizing activity. Anti-HCV hyperimmune globulin could be
      prepared from anti-HCV-positive blood units and could be used to protect sexual
      partners and in other at-risk situations of exposure to HCV infection.

PMID- 15468433
TI  - Coinfection with HTLV-I and HIV: increase in HTLV-I-related outcomes but not
      accelerated HIV disease progression?
AB  - Human T-lymphotropic virus type I (HTLV-I) and HTLV-II have been postulated to
      accelerate disease progression in patients coinfected with HIV. However, recent
      evidence suggests that HTLV-II has no effect on HIV disease progression. In
      addition, it has recently been reported that HIV viral load was not increased in
      subjects coinfected with HTLV-I, suggesting that the biologic basis for the
      hypothesis does not exist. Several recent studies in Brazil, however, suggest
      that coinfection with HTLV-I and HIV has substantial medical consequences. For
      example, coinfection was associated with a higher CD4 lymphocytes count following
      adjustment for HIV viral load or HIV clinical stage. In addition, coinfected
      subjects have a high prevalence of clinical significant myelopathy. The effect of
      other putative viruses as cofactors in HIV disease progression is also discussed.

PMID- 15468434
TI  - The treatment of oropharyngeal candidiasis in HIV-infected patients with oral
      amphotericin B suspension.
AB  - Oropharyngeal candidiasis (OPC) is the most frequent opportunistic infection
      associated with HIV infection. Therapies such as topical clotrimazole and
      nystatin, as well as oral azoles, which had previously been effective prior to
      the advent of HIV, are increasingly only partially effective in OPC in HIV
      infection. The effectiveness of oral amphotericin B suspension for OPC is
      described in 17 HIV-infected patients whose response to other therapies had been
      unsatisfactory. Three patients yielded isolates of Candida albicans with a
      minimum inhibitory concentration (MIC) to fluconazole of >/=16 microg/mL. Eleven
      patients received amphotericin B suspension monotherapy. Of the 17 patients, the
      symptoms of six resolved entirely, seven patients partially responded, and four
      failed therapy. These data suggest that amphotericin B suspension may be a useful
      additional therapy for OPC in HIV-infected patients.

PMID- 15468435
TI  - Predictors of survival in children with acquired immunodeficiency syndrome in
      Italy, 1983 to 1995.
AB  - To evaluate length and predictors of survival among children with AIDS, 529
      pediatric cases diagnosed in Italy from 1983 to August 1995 were reviewed. Data
      were analyzed using Kaplan-Meier curves and the Cox proportional hazards
      regression model. Various survival patterns were subsequently analyzed. All
      survival analyses were truncated on March 1, 1996. Cases were examined by gender,
      age at diagnosis, HIV transmission category, type and number of the first AIDS
      defining diseases, level of immunosuppression at AIDS diagnosis, HIV transmission
      category of the mother, and period of diagnosis. The overall median survival time
      was approximately 24 months. There wer no significant differences in survival by
      gender, HIV transmission category, mother's risk factor, or period of diagnosis.
      The Kaplan-Meier analysis showed the greatest differences in survival time
      between children less than 6 months of age at diagnosis (median survival 6.4
      months) and all others (median 28.7 months). Children with recurrent bacterial
      infections or lymphoid interstitial pneumonia (LIP) had a survival time at least
      four times longer than those with Pneumocystis carinii pneumonia (PCP),
      mycobacteriosis, cytomegalovirus, tumors, or progressive multifocal
      leukoencephalopathy. At the multivariate analysis, the risk of death was lower
      among children with LIP (Relative Hazard [RH] 0.72) compared with other
      opportunistic diseases, whereas age less than 6 months, diagnosis of PCP or of
      two or more diseases, and severe immunosuppression at diagnosis increased the
      risk of death. Both demographic factors (age) and clinical factors (type and
      number of initial diseases, level of immunosuppression) were found to be
      independent predictors of a poor prognosis in children with AIDS. This
      information may be of use in improving prognosis and planning healthcare and
      treatment.

PMID- 15468436
TI  - HIV-positive women over fifty: how they cope.
AB  - Healthcare providers may not understand the special issues and needs of older
      persons with HIV. This article directs particular attention to the unique
      reactions of older women to an HIV-positive diagnosis. Through their
      participation in a support group, some older HIV-positive women have been able to
      adapt to their illness with a variety of coping styles. Illustrations of the ways
      these women meet challenges both individually and as a group are presented. The
      article concludes with simple messages from the women to the members of the
      medical community.

PMID- 15468437
TI  - HIV and STD prevention update. New CDC guidelines for HIV postexposure
      prophylaxis.

PMID- 15468438
TI  - 12th World AIDS Conference: pointing out the gaps.

PMID- 15468439
TI  - Dealing with fever of unknown origin in an HIV-infected patient.

PMID- 15468440
TI  - BCG lymphadenitis in an HIV-infected child 9.5 years after vaccination.
AB  - Complications of Bacillus Calmette-Guerin (BCG) vaccination have been reported in
      immunocompetent as well as in immunocompromised individuals. Severe and/or late
      complications have been associated with impairment of cell-mediated immunity. A
      case of BCG lymphadenitis in a vertically infected HIV-positive boy 9.5 years
      after vaccination is presented. The vaccination was performed within the first
      week of life, the HIV status of the mother being unknown. When the boy was 2.5
      years old, his HIV infection was diagnosed after his mother had died from AIDS.
      At that time his CD4 count was 739 cells/microL. In the course of the following
      years, his CD4 count declined steadily, until it reached a low of about 20
      cells/microL at the age of 5.5 years. He was troubled with recurring respiratory
      infections and one incidence of severe pancreatitis. Apart from that, he was in
      stable condition and led a more or less normal life. At the age of 9.5 years he
      developed lymphadenitis in his left axilla. The node was examined via biopsy, and
      the appropriate tests showed an infection with Mycobacterium bovis BCG variety.
      The CD4 count at that time was 16 cells/microL, polymerase chain reaction showed
      220,000 RNA copies/mL. There were no signs of dissemination. Antitubercular
      agents were administered, and an antiretroviral combination therapy was started.
      The patient was discharged from the hospital after approximately 2 months. After
      an uneventful period of 9 months, the boy, still on antitubercular medicine,
      exhibited a secreting fistula in his left axilla, again due to Mycobacterium
      bovis, BCG variety. The fistulous tissue was removed surgically, and the
      antitubercular treatment was given intravenously for almost 3 months before being
      changed to an oral application. In addition, the antiretroviral regimen was
      completely exchanged. The case presented illustrates that there is a risk of very
      late complications in HIV-infected individuals, even when they are vaccinated
      when they are asymptomatic newborns. Although the risk seems low, one has to be
      aware of the problem because timely treatment is probably essential to prevent
      dissemination of the infection. Late complications of BCG vaccinations are most
      likely to be detected in countries with high medical standards, where HIV
      infected children are surviving for longer periods of time.

PMID- 15468441
TI  - Candidal meningitis in HIV-infected patients.
AB  - Candida meningitis is considered a rare event in HIV-infected patients, and
      little is known about risk factors, clinical presentation, therapy of choice, or
      outcome in this population. In a review of 14 cases, we observed a low frequency
      of the disease, a strong association to other well-known risk factors for
      systematic candidiasis, such as intravenous drug use, and a chronic course and
      clinical features that mimic those of cryptococcal or tuberculous meningitis.
      Although the role of fluconazole treatment remains to be defined, the combination
      of amphotericin B with flucytosine offers a survival rate similar to non-HIV
      infected patients. In addition, the use of suppressive therapy with fluconazole
      for a prolonged period after clinical improvement seems recommendable.

PMID- 15468442
TI  - An update on drug interactions with zidovudine.
AB  - Zidovudine remains one of the most commonly prescribed agents for patients with
      HIV infection. A variety of drug interactions have been reported that may alter
      blood levels of zidovudine and concomitantly administered drugs or may involve
      overlapping toxicities. Several concomitant medications have been shown to alter
      the plasma concentrations of zidovudine, although most of these interactions are
      not thought to be clinically important. Use of agents that share the bone marrow
      suppressive properties of zidovudine require additional monitoring for the
      development of hematologic toxicity. An understanding of potential mechanisms and
      important zidovudine-related interactions will aid in the optimal care of the HIV
      infected patient.

PMID- 15468443
TI  - Reliability of laboratory markers of HIV-1 infection in Argentinian infants at
      risk of perinatal infection.
AB  - Early and accurate diagnosis of HIV-1 infection in infants born to HIV-1
      seropositive mothers is of great importance. Polymerase chain reaction (PCR), HIV
      culture, and p24 antigen detection assays were evaluated for their ability to
      detect the presence of HIV in 195 infants at risk of perinatal infection. Using
      the Centers for Disease Control and Prevention guidelines for assessing HIV
      infection status in children younger than 18 months, 70 infants (36%) were
      diagnosed as HIV-1 infected and 125 (64%) lacked virologic and clinical evidence
      of infection. PCR and HIV culture were the most sensitive laboratory markers,
      detecting 100% and 98% of positive samples, respectively, regardless of age at
      testing. HIV-1 p24 antigen assay was detected in 26 of 38 positive samples but
      not in negative samples. PCR was performed with three different sets of primers
      (SK38/SK39-SK19-gag, SK68/SK69-SK70-env, and SK150/SK431-SK102-gag). The
      sensitivity/specificity of the individual assays were for SK19, 96.1%/94.25%;
      SK70, 89.6%/100%; and SK102, 100%/100%. A sample was considered HIV-1 positive
      when two positive PCR results were obtained with two different pairs of primers,
      and negative if the sample was negative when three sets of primers were used.
      False-positive results were occasionally obtained with probe SK19 in six
      seroreverter infants before serologic status was known. This suggested that the
      infection was caused by nonreplicative strains or were false-positive results
      probably by nonspecific amplification due to cross-reaction with other
      microorganisms; contamination was discarded because there was no specific
      amplification with the other two primers. All the HIV-1-infected infants were
      correctly identified with PCR; all except one could be identified with coculture
      and only 68.4% were confirmed with p24 antigen assay. No seroreverter infant was
      misdiagnosed using the criteria selected.

PMID- 15468444
TI  - Prisoners' knowledge and attitude toward prophylactic treatment and therapy.
AB  - Identifying factors that hinder an inmate's compliance with Pneumocystis carinii
      pneumonia (PCP) prophylaxis therapy can be critical in preventing or decreasing
      the occurrence of PCP in this population. Anticipated factors include lack of
      knowledge about PCP and its proposed treatment, fear of the adverse effects of
      prophylaxis therapy, and lack of trust in the correctional facility medical team.
      Structured interviews were administered to HIV-positive male inmates chosen
      randomly (n = 104) at a medium- to maximum-security medical correctional facility
      located in the western portion of the United States. A basic "HIV 101 and Early
      Intervention" program encompassed the presentation of HIV facts and knowledge as
      well as safer sex practices. The results revealed that 95% of the respondents
      were knowledgeable about PCP and the side effects of their medications, and 56%
      of the respondents were afraid of the medications' side effects. Significant
      differences based on age were recorded for several specific knowledge questions,
      including the preventable nature of PCP.

PMID- 15468446
TI  - HIV/AIDS case histories: diagnostic problems. Diagnosis: Kaposi's sarcoma.

PMID- 15468445
TI  - Needle sharing and high-risk sexual behaviors among IV drug users in Southern
      Thailand.
AB  - This study sought to determine the prevalence of needle sharing and high HIV risk
      sexual behaviors and to identify characteristics associated with these practices
      in southern Thailand. Data were obtained using a structured questionnaire from
      298 male intravenous drug users (IVDUs) seen in a methadone clinic during the
      previous year. The prevalence of HIV was 37%, and that of needle-sharing in the
      preceding months was 45%, although only 10% claimed to have had unsafe sex with a
      casual partner or prostitute in the same period. Determinants for needle sharing
      included shorter duration of drug injection, diminished knowledge of HIV
      prevention, a carefree attitude toward risk of HIV infection, and lower levels of
      income. Young single IVDUs with a low knowledge of HIV prevention were most
      likely not to use a condom. In conclusion, needle sharing among the study
      subjects was still a common practice, whereas high HIV risk sexual behavior was
      not. Attitudinal change may be necessary to reduce needle-sharing behavior and
      not just information on disease transmission.

PMID- 15468447
TI  - HIV and STD prevention update. Multisite HIV prevention trial.

PMID- 15468448
TI  - Ten books.

PMID- 15468449
TI  - [Dried blood spot Vitamin A determination by high pressure liquid chromatography
      with electrochemical detection].
AB  - In tropical countries. vitamin A deficiency is one of the most important dietary
      deficiencies. Its monitoring usually involves analysis of retinol after
      venipuncture with some difficulties (disease transmission, religious belief).
      Sample collection on Dried Blood Spot (DBS) is less invasive and safer. Sample
      storage is easier. We developed a liquid chromatography method with
      electrochemical detection to measure DBS retinol. Retinol acetate was used as an
      internal standard. The method is linear up to 2.5 microM with a detection limit
      of 0.04 microM. Precision is below 10% and DBS retinol recovery overage is 90%.
      DBS retinol concentration decreased during 7 days after sampling, it is necessary
      to wait this delay before to determine vitamin A concentrations. In Congolese
      children DBS retinol measurement showed a severe vitamin A deficiency in 8% of
      them. This percentage is closely correlated with clinical parameters.

PMID- 15468451
TI  - [Safety of anti-COX 2?].

PMID- 15468450
TI  - Re: Jockusch and Dress 'From sphere to torus: a topological view of the metazoan
      body plan' (Bull. Math.Biol. (2003) 65, 57-65).

PMID- 15468452
TI  - [iRNA against the flu].

PMID- 15468453
TI  - [CFTR traffic: there is Rab!].

PMID- 15468454
TI  - [EPO without doping].

PMID- 15468455
TI  - ["Proteic" therapy for dystrophic bullous epidermolysis].

PMID- 15468456
TI  - [Capacity of bone marrow stem cells to differentiate themselves into epithelial
      cells: a really fusional controversy!].

PMID- 15468458
TI  - ["Normal" PSA levels ignore 15% of prostate cancers].

PMID- 15468457
TI  - [Losing abdominal fat with liposuction does not improve the metabolic syndrome].

PMID- 15468459
TI  - [No need of angiotensin II to activate AT-1 receptors].

PMID- 15468460
TI  - Pathogens in decay.

PMID- 15468461
TI  - HIV vaccine trial halted.

PMID- 15468462
TI  - AIDS funding.

PMID- 15468464
TI  - Consensus-seeking roundtable on placebos in clinical research.

PMID- 15468463
TI  - Corrigendum to "gender in obsessive-compulsive disorder: clinical and genetic
      findings" [Eur. Neuropsychopharmacol. 14 (2004) 105-113].
AB  - BACKGROUND: There is increasing recognition that obsessive-compulsive disorder
      (OCD) is not a homogeneous entity. It has been suggested that gender may
      contribute to the clinical and biological heterogeneity of OCD. METHODS: Two
      hundred and twenty patients (n=220; 107 male, 113 female) with DSM-IV OCD (age:
      36.40 +/- 13.46) underwent structured interviews. A subset of Caucasian subjects
      (n=178), including subjects from the genetically homogeneous Afrikaner population
      (n=81), and of matched control subjects (n=161), was genotyped for polymorphisms
      in genes involved in monoamine function. Clinical and genetic data were
      statistically analyzed across gender. RESULTS: Compared with females, males with
      OCD (1) had an earlier age of onset, and a trend toward having more tics and
      worse outcome, (2) had somewhat differing patterns of OCD symptomatology and axis
      I comorbidity, and (3) in the Caucasian group, were more likely to have the high
      activity T allele of the EcoRV variant of the monoamine oxidase A (MAO-A) gene
      compared to controls, and (4) in the Afrikaner subgroup, were more frequently
      homozygous for the G allele at the G861C variant of the 5HT1Dbeta gene than
      controls. Females with OCD (1) reported more sexual abuse during childhood than
      males, (2) often noted changes in obsessive-compulsive symptoms in the
      premenstrual/menstrual period as well as during/shortly after pregnancy, and with
      menopause, and (3) in the Caucasian subgroup, were more frequently homozygous for
      the low activity C allele of the EcoRV variant of the MAO-A gene compared to
      controls, with this allele also more frequent in female patients than controls.
      CONCLUSION: This study supports the hypothesis that gender contributes to the
      clinical and biological heterogeneity of OCD. A sexually dimorphic pattern of
      genetic susceptibility to OCD may be present. Further work is, however, needed to
      delineate the mechanisms that are responsible for mediating the effects of
      gender.

PMID- 15468465
TI  - Ministerial action plan on research ethics and scientific integrity.

PMID- 15468466
TI  - Issues in consent.

PMID- 15468467
TI  - Maximizing the effectiveness of REBs.

PMID- 15468468
TI  - Protecting human subjects.

PMID- 15468469
TI  - Presentation to the standing committee on health, Ottawa, December 7, 1999.

PMID- 15468470
TI  - An assessment of educational needs in research ethics.

PMID- 15468471
TI  - Design, synthesis and antibacterial activity studies of model peptidess of
      proline/arginine-rich region in bactenecin7.
AB  - Bactenecin 7 (Bac7), a cationic antibacterial peptide, contains a repeating
      region of Xaa-Pro-Arg-Pro (Xaa = hydrophobic residue). To investigate the
      structure and property of a Pro/Arg-rich region, e synthesized a series of
      peptides, Xaa-Pro-Arg-Pro (Xaa = Gly, Arg, Leu, Ile, and Phe) as models and
      characterized . The conformational preferences of these peptides in water and
      trifluoroethanol were examined by circular dichroism. The results suggest the
      presence of largely poly(Pro)-II helical conformation in aqueous and
      trifluoroethanol solutions. Their antibacterial activity against gram-negative
      bacteria such as Escherichia coli, Klebsiella Pneumoniae, Pseudomonas aeruginosa,
      and Escherichia coliHB101, and gram-positive bacteria such as Staphylococcus
      aureus were measured at various peptide concentrations. Two of our synthetic
      tetrapeptide fragments containing Gly and Arg were efficiently killed with gram
      positive bacteria, Staphylococcus aureus, at the concentration level of 200
      microg/mL.

PMID- 15468472
TI  - The implications of differing methods of utility assessment for patient-specific
      decision-analytic tools.

PMID- 15468473
TI  - The case against perfection: what's wrong with designer children, bionic
      athletes, and genetic engineering.

PMID- 15468474
TI  - Realigning Catholic priorities: bioethics and the common good.

PMID- 15468475
TI  - Medical school is sued over research.

PMID- 15468476
TI  - The promise and peril of direct-to-consumer prescription drug promotion on the
      Internet.

PMID- 15468477
TI  - The more things change, the more they stay the same: an analysis of the impact of
      the HIPAA Privacy Rule on Illinois mental health providers.

PMID- 15468478
TI  - A woman's choice? On women, assisted reproduction and social coercion.
AB  - This paper critically discusses an argument that is sometimes pressed into
      service in the ethical debate about the use of assisted reproduction. The
      argument runs roughly as follows: we should prevent women from using assisted
      reproduction techniques, because women who want to use the technology have been
      socially coerced into desiring children--and indeed have thereby been harmed by
      the patriarchal society in which they live. I call this the argument from
      coercion. Having clarified this argument, I conclude that although it addresses
      important issues, it is highly problematic for the following reasons. First, if
      women are being coerced to desire to use AR, we should eradicate the coercive
      elements in pro-natalist ideology, not access to AR. Second, the argument seems
      to have the absurd implication that we should prevent all women, whether fertile
      or not, to try to have children. Third, it seems probable that women's welfare
      will be greater if we let well informed and decision-competent women decide for
      themselves whether they want to use AR.

PMID- 15468479
TI  - A neglected solution to the problem of the metaphysical and moral status of the
      human-animal chimera.

PMID- 15468480
TI  - Lethal injection: the medical charade.

PMID- 15468481
TI  - When a family member changes their mind regarding the DNR order: the importance
      of documentation.

PMID- 15468482
TI  - Human embryos, "twinning," and public policy.

PMID- 15468483
TI  - When names make claims: ethical issues in medical device marketing.

PMID- 15468484
TI  - Knowledge and the governance of biotechnology.

PMID- 15468485
TI  - Ordering life: law and the normalization of biotechnology.

PMID- 15468486
TI  - Expert discourses of risk and ethics on genetically manipulated organisms: the
      weaving of public alienation.

PMID- 15468488
TI  - Should we add "xeno" to "transplantation"?
AB  - Proponents of xenotransplantation hope that it will provide organs to fill the
      gap between the demand for and supply of organs for transplant. The scientific
      obstacles to transplanting animal organs into humans are daunting, as are the
      moral, political, and policy issues. Among them are concerns about animal rights
      and welfare, patient acceptance and informed consent, and broader public health
      issues, such as the cost-efficient deployment of scarce resources and the risk of
      disease in third parties. The latter is, in my view, the most immediately urgent
      issue. Pigs, the current animal of choice, carry many bacterial and viral
      pathogens, and it is currently impossible to assess the risk of disease to human
      populations. Because of this risk, a moratorium on xenotransplantation is
      necessary to protect public health; it is also questionable whether the
      technology, if successful, would be the most cost-effective way to promote
      health.

PMID- 15468489
TI  - The FDA's proposal for public disclosure of adverse events in gene therapy
      trials.
AB  - In January 2001, the Food and Drug Administration (FDA) proposed annual public
      disclosure of adverse events during gene therapy and xenotransplantation trials.
      The proposed policy raises the following questions: (1) Is the reformed policy in
      accord with the FDA's long-standing informed consent policies? (2) Why pair gene
      therapy trials and xenotransplantation trials in the revised guidelines? (3) Why
      single out these trials for public disclosure of adverse events? Each question is
      examined, and three conclusions are drawn. First, the FDA's own policies on
      informed consent require prompter public disclosure of adverse events. Second,
      the coupling of gene therapy and xenotransplantation trials entails a conceptual
      mistake in the types of communities that are harmed by each therapy's related
      adverse events. Third, all clinical trials merit such public disclosure of
      adverse events, not only gene therapy and xenotransplantation trials.

PMID- 15468490
TI  - Unusually difficult challenges in human-subjects research.

PMID- 15468491
TI  - History and ethics in public health research.

PMID- 15468492
TI  - Occupational and environmental health: towards an environmentally inclusive
      bioethics.

PMID- 15468493
TI  - Should epidemiologists and other health scientists become advocates for social
      policies?

PMID- 15468494
TI  - The science of cloning, the right of reproduction, and professional
      responsibility.

PMID- 15468495
TI  - Possibilities for nursing care.

PMID- 15468496
TI  - Slogans for body parts: a look at campaigns to increase organ donation.

PMID- 15468497
TI  - Disability and justice: a pluralistic account.

PMID- 15468498
TI  - Does the non-identity problem block a class of arguments against cloning?
AB  - One class of argument against cloning human beings in the contemporary literature
      focuses on the bad consequences that will befall the clone or "later-twin." In
      this paper I consider whether this line of argumentation can be blocked by
      invoking Parfit's non-identity problem. I canvass two general strategies for
      solving the non-identity problem: a consequentialist strategy and non
      consequentialist, rights based strategy. I argue that while each general strategy
      offers a plausible solution to the non-identity problem as applied to the cases
      most frequently discussed in the non-identity problem literature, neither
      provides a reason for putting aside the non-identity problem when applied to
      cloning. I conclude (roughly) that the non-identity problem does serve to block
      this class of argument against cloning.

PMID- 15468499
TI  - Lower income Hindu women's attitude towards abortion: a case study in urban
      India.
AB  - After a brief discussion of Hindu views on abortion as reflected in classical
      Hindu philosophical and religious texts, this article examines, from an
      interdisciplinary perspective, current social attitudes towards abortion among
      lower-income Hindu women in Calcutta and attempts to identify the reasons for the
      striking disparity between traditional and modern Hindu views. Does Hindu dharma
      have the regulatory power it wielded in the past? What accounts for the changing
      face of mores in urban centers like Calcutta? These and related issues are the
      focus of this essay.

PMID- 15468500
TI  - Unseen failings of primate research.

PMID- 15468501
TI  - UK cloners target diabetes cure.

PMID- 15468502
TI  - Ma adam va-teda-ehu: halakhic criteria for defining human beings.

PMID- 15468503
TI  - Uterine transplantation and the case of the mistaken question.

PMID- 15468504
TI  - Halakhic parameters for removing patients from a ventilator.

PMID- 15468505
TI  - Survey of recent halakhic periodical literature: genetic engineering.

PMID- 15468506
TI  - Medicate-to-execute: current trends in death penalty jurisprudence and the perils
      of dual loyalty.

PMID- 15468507
TI  - Field of genes: the politics of science and identity in the Estonian Genome
      Project.
AB  - This case study of the Estonian Genome Project (EGP) analyses the Estonian policy
      decision to construct a national human gene bank. Drawing upon qualitative data
      from newspaper articles and public policy documents, it focuses on how proponents
      use discourse to link the EGP to the broader political goal of securing Estonia's
      position within the Western/European scientific and cultural space. This dominant
      narrative is then situated within the analytical notion of the "brand state",
      which raises potentially negative political consequences for this type of market
      driven genomic research. Considered against the increasing number of countries
      engaging in gene bank and/or gene database projects, this analysis of Estonia
      elucidates issues that cross national boundaries, while also illuminating factors
      specific to this small, post-Soviet state as it enters the global biocybernetic
      economy.

PMID- 15468508
TI  - Perfecting people: selective breeding at the Oneida Community (1869-1879) and the
      eugenics movement.
AB  - The paper describes the selective breeding experiment which took place in the
      Bible Communist Oneida Community in New York State. The Community was founded in
      1848 by John Humphrey Noyes and grew to some three hundred members. It disbanded
      in 1880 and became a joint stock company, Oneida Ltd., which today is a
      multinational cutlery manufacturer. Between 1869 and 1880 there was a selective
      breeding programme ("stirpiculture") with parents chosen for intellectual,
      physical and spiritual characteristics. Fifty-eight children were born. The
      programme was inspired by Noyes' theology of Perfectionism, Plato's Republic,
      agricultural selective breeding and concerns about human heredity. It was later
      justified by Noyes with the writings of Darwin and Galton. The children were
      followed up and deemed to be superior in physique, intellect, health and other
      characteristics. Though it attracted attention in its day, the experiment had
      little influence on the later eugenic movements in the USA and the UK. It is
      argued that this was because the Community's system of "complex marriage" and the
      arranged matings were an unacceptably radical challenge to the conventional
      notions of love and marriage which dominated these later eugenics movements. The
      first generation of descendants' attempts to bury aspects of the history of the
      Community also contributed a lack of knowledge of the experiment and its outcome.

PMID- 15468509
TI  - [Progress in the prevention and control of whooping cough].

PMID- 15468510
TI  - [Study on the meteorologic epidemiology and its prospect].

PMID- 15468511
TI  - A protocol for quantitative measurement of light intensity levels in food service
      operations.
AB  - Food service workers conduct informal inspections of food service operations to
      ensure that food contamination does not occur. This activity requires proper
      lighting. Compliance with lighting standards is usually assessed by a
      qualitative, visual inspection method. Recent studies suggest, however, that
      qualitative inspections only minimally reduce risks of foodborne-disease
      outbreaks. To evaluate the efficacy of qualitative lighting level assessments,
      this study quantitatively measured lighting in walk-in coolers and at food
      preparation counters in 57 food service establishments. Measurements were
      conducted alongside regular sanitarian inspections. Of the 55 walk-in coolers
      evaluated, 12 had fluorescent and 43 had incandescent lighting. The geometic mean
      (GM) light level at the center of coolers with fluorescent lighting was 15.3 foot
      candles (ft-c) (range: 6.4-85.5). Seventy-five percent of these coolers met the
      standard of 10 ft-c. The GM level at the center of coolers with incandescent
      lighting was 3.43 ft-c (range: 1.0-16.7). Seven percent of the incandescently lit
      coolers met the standard. Inadequate cooler illumination was indicated on only
      four sanitarian inspection reports. The GM level at 185 food preparation counters
      was 38.7 ft-c (range: 2.9-196.8). At 47 percent of the establishments, no
      counters met the 50 ft-c standard. Twenty-three percent of the establishments met
      the standard at all evaluated counters. Inadequate counter illumination was noted
      only once by a sanitarian. Qualitative assessments did not identify most of the
      lighting standard violations. Additional training and integration of quantitative
      assessments into inspections are warranted. Fluorescent lighting produced
      significantly higher light levels and pass rates in coolers and should become the
      lighting type of choice. Finally, gaps in the standards were identified and
      should be addressed.

PMID- 15468512
TI  - The efficacy of cleaning products on food industry surfaces.
AB  - The increased incidence of foodborne illness and the growing use of chemical
      sanitizers in the food industry led the authors to an investigation of
      alternative, chemical-free methods of sanitizing surfaces using fiber cloths with
      hot water. The sanitizing performance of kitchen fiber cloths and all-purpose
      fiber cloths sanitized with hot water at 167 degrees F (75 degrees C) was
      compared with that of generic cloths such as antibacterial cloths and cleaning
      cloths sanitized with hot water at 167 degrees F (75 degrees C) or chemical
      sanitizers--quaternary ammonium compound (QAC) and hypochlorite. The QAC
      sanitizer resulted in the lowest overall concentrations of Staphylococcus aureus
      and Escherichia coli. The sanitizing performance of the kitchen fiber cloths was
      similar to that of the antibacterial cloths (S. aureus: p = .144; E. coli: p =
      .120) and cleaning cloths (S. aureus: p = .297; E. coli: p = .062) sanitized with
      QAC. Use of the fiber cloths resulted in lower concentrations of bacteria on
      stainless-steel kitchen surfaces, compared with the use of the generic cloths
      sanitized with hot water at 167 degrees F (75 degrees C). Concentrations of
      bacteria on the surfaces after use of the all-purpose fiber cloths were similar
      to concentrations of bacteria after use of the generic cloths sanitized with
      hypochlorite.

PMID- 15468513
TI  - Safe handling of drinking water, ice, and dispensers.

PMID- 15468514
TI  - Terrorism response and the environmental health role: the million-dollar (and
      some) question.

PMID- 15468515
TI  - Running the nerve gas gauntlet.

PMID- 15468516
TI  - Listeria monocytogenes--questions and answers.

PMID- 15468517
TI  - It can be done--making the invisible visible.

PMID- 15468518
TI  - The future of expanded school mental health.

PMID- 15468519
TI  - Is recent hospitalization a marker for moderate-severe persistent asthma in
      school children?

PMID- 15468520
TI  - The role of CSHPs in preventing child abuse and neglect.

PMID- 15468521
TI  - A pilot project: pediatric resident and medical student training rotation in
      school-based health clinics.

PMID- 15468522
TI  - Why teach health education.

PMID- 15468523
TI  - The WHO cross-national study of health behavior in school-aged children from 35
      countries: findings from 2001-2002.

PMID- 15468524
TI  - Teaching at the secondary level: wisdom from veteran health educators.
AB  - This qualitative study explored factors that helped veteran public school health
      educators sustain enthusiasm in the classroom throughout their careers. Twelve
      Caucasian participants, seven men and five women with 18 to 28 years of public
      school teaching experience (mean age = 49 years, mean experience = 24 years),
      were interviewed. Participants were selected from teachers with at least 18 years
      experience who lived within 60 minutes of Salt Lake City, Utah. Semi-structured,
      individual interviews addressed four questions: Why did participants enter
      teaching? What are some challenges of teaching? What factors contribute to
      successful teaching? What factors contributed to participants' longevity in
      teaching? A decision to teach was based primarily on having an influential
      teacher. The greatest challenges were discipline and diversity. Factors related
      to successful teaching also contributed to longevity in teaching. These factors
      included staying current with information and technology, supportive colleagues,
      and sharing oneself with students and colleagues. Those interested in a teaching
      career, and those already invested in teaching, can learn from these veterans in
      terms of skills and values.

PMID- 15468525
TI  - Impact of school nurse case management on students with asthma.
AB  - This project determined asthma prevalence in a large school district, absentee
      rates, and potential effects of school nurse case management for student asthma
      over three years. Data were derived from an asthma tracking tool used by nurses
      in one school district for every student reported as having asthma by their
      parent. School nurses began collecting data in their schools in 1999-2000 when an
      asthma-management protocol was first developed. Nurses documented perceived
      asthma severity for each student, presence of medication and peak flow meters in
      school, and case management activities provided. This data base was cross matched
      with percentage of days students were absent for any illness. Prevalence of
      asthma, based on school nurse records of parent report, was between 5.1% to 6.2%
      during the three years. Between 13.5% and 15% were moderate or severe. Students
      with asthma were absent between one-half to one and one-quarter days more often
      than those without asthma. In year three, 39% of students with asthma had
      medication at school, and 12% had a peak flow meter. Contacting a parent was the
      nurse case management activity provided for the largest number of students (27%
      of students with asthma), followed by asthma education (16.5%), contact with
      physician (6%), and home visits (1%). Students who received at least one school
      nurse case management intervention were more likely the next year to have an
      asthma medication at school, to use a peak flow meter at school, and to have a
      change in asthma severity. School nurse case management activity had no
      association with student absences. Availability of medication and peak flow
      meters at school was low, suggesting standards of care for asthma were not
      followed. School nurse case management, when performed outside a project or
      intervention, offers a promising strategy to improve asthma management.

PMID- 15468526
TI  - Using Achievement Goal Theory to assess an elementary physical education running
      program.
AB  - Using Achievement Goal Theory as a theoretical framework, this study examined an
      elementary physical education running program called Roadrunners and assessed
      relationships among achievement goals, perceived motivational climate, and
      student achievement behavior. Roadrunners promotes cardiovascular health,
      physical active lifestyles, and mastery behaviors such as persistence and effort.
      Students were required to run/walk once a week during the school year in their
      regularly scheduled physical education classes. Participants included 116 fourth
      graders (67 boys, 49 girls), who participated in Roadrunners since kindergarten.
      Near the end of spring semester, students completed a 36-item questionnaire
      assessing achievement goals and perceived motivational climate of Roadrunners.
      Student persistence/effort was assessed by the number of run/walk laps over the
      year-long program. Performance was measured by a timed, one-mile run. Results
      revealed the mastery goal related positively to student persistence/effort for
      Roadrunners and to their one-mile run performance. Interaction between the
      mastery goal and perception of a mastery-focused climate emerged as a positive
      predictor of student one-mile run performance. Results provided additional
      empirical support for mastery goals and perceptions of a mastery-focused climate
      as beneficial to student motivation and learning.

PMID- 15468527
TI  - A rapid genotyping method for the vivax malaria transmission-blocking vaccine
      candidates, Pvs25 and Pvs28.
AB  - The antigenic diversity observed in many vaccine candidates is one of the
      difficulties to design effective malaria vaccine. Since it is prerequisite to
      survey genetic polymorphism of the vaccine candidate antigens for the vaccine
      development, it is necessary to establish efficient screening method to detect
      the genetic polymorphism from a large number of samples. Here, we have
      established efficient polymerase chain reaction-single strand conformational
      polymorphism (PCR-SSCP) method to detect nucleotide diversity of the malaria
      transmission-blocking vaccine candidates Pvs25 and Pvs28. We can distinguish all
      4 haplotypes of Pvs25 by this method. By introducing BsmI-digestion step for
      Pvs28, we can distinguish 15/16 haplotypes by single electrophoresis. Since this
      method requires neither sequencing nor radioisotope labeling, it will be easy to
      transfer the method into a field based high throughput screening of genetic
      polymorphism.

PMID- 15468528
TI  - Influence of H2 complex and non-H2 genes on progression of cutaneous lesions in
      mice infected with Leishmania amazonensis.
AB  - Susceptibility to infection with Leishmania amazonensis promastigotes was
      examined in six B10 congenic mouse strains, including C57BL/10J (H2b), B10.BR
      (H2k), B10.M (H2f), B10.S (H2s), B10.RIII (H2r), and B10.D2 (H2d). All strains of
      mice developed skin nodules with punch-out ulcers by 8 weeks post-infection, but
      B10.M and B10.S mice showed resolution of cutaneous leishmaniasis lesions by 16
      weeks post-infection. In addition, the skin lesions were much larger in BALB
      congenic mice than in B10 and C3H mice, even though these mice share the same H2
      haplotypes. These results suggest that H2 complex controls the growth of L.
      amazonensis in cutaneous lesions, and that non-H2 genes inherited by BALB
      congenic mice have a more potent role than the H2 complex in lesion progression.

PMID- 15468529
TI  - Comparison of rDNA sequences from colchicine treated and untreated sporocysts of
      Phyllodistomum folium and Bucephalus polymorphus (Digenea).
AB  - The most frequently used antimitotic agent in cytogenetic studies is colchicine.
      We investigated whether the initial treatment of trematodes for karyological
      analysis with colchicine would have mutagenic or degradational effect on rDNA
      sequences. Dreissena polymorpha is the intermediate host of Phyllodistomum folium
      and Bucephalus polymorphus, and the sporocyst stage of these trematode species
      develop, respectively, in the gills and gonads of this mussel. Sporocysts of P.
      folium and B. polymorphus were obtained from D. polymorpha collected from
      waterbodies in Belarus and in Lithuania. 5.8S and 28S rDNA genes, ITS1 and ITS2
      of P folium and B. polymorphus were sequenced and compared, and no nucleotide
      sequence differences between colchicine treated and untreated trematodes were
      found. Based on these results, we conclude that colchicine treatment for 3-5 h
      has no mutagenic or degradational effect on rDNA sequences. During the course of
      this investigation, two genetically different P. folium samples were noted in
      Belarus.

PMID- 15468530
TI  - Two new species of bucephalids (Digenea: Bucephalidae) parasitic in freshwater
      fishes of Argentina.
AB  - Two new species of bucephalids (Digenea: Bucephalidae) were found parasitizing
      freshwater fishes of Argentina. Prosorhynchoides cambapuntaensis sp. n. from
      Salminus maxillosus (Characidae) is characterised by the tegument covered with
      two kinds of spines, scale-like spines anteriorly and fine spines posteriorly;
      uterine loops reaching the vitelline arch in the pre-oral region; and the
      Laurer's canal short, opening dorsally immediately posterior to the ovary.
      Rhipidocotyle santanaensis sp. n. from Acestrorhynchus pantaneiro
      (Acestrorhynchidae) is characterised by the rhynchus with two lateral
      projections; the testes arranged in tandem or slightly diagonal; and the
      vitelline follicles forming an arch in the pre-oral region.

PMID- 15468532
TI  - An experimental model for amoebic abscess production in the cheek pouch of the
      Syrian golden hamster, Mesocricetus auratus.
AB  - A new experimental model was developed in hamsters for amoebic abscess caused by
      Entamoeba histolytica. E. histolytica trophozoites were cultured in a liquid
      axenic medium, and then injected intradermally into the cheek pouch of the Syrian
      golden hamster, Mesocricetus auratus. Inoculation consistently resulted in
      abscess formation at the site in 20 of 22 (91%) study animals. The amoebic nature
      of the abscesses was confirmed by light microscopy and histopathologic
      examination. Abscess formation was maximal at day 12 post-inoculation. Potential
      applications of this simple and reliable model include further elucidation of the
      pathogenesis of invasive amoebiasis, studies of the host response to amoebae, and
      in vivo evaluation of chemotherapeutic agents that show in vitro efficacy against
      E. histolytica.

PMID- 15468531
TI  - Molecular cloning and characterization of Trypanosoma vivax alternative oxidase
      (AOX) gene, a target of the trypanocide ascofuranone.
AB  - Trypanosoma vivax causes nagana disease in cattle. Since T. vivax is transmitted
      not only by tsetse flies but also by other biting flies (non-cyclic
      transmission), the parasite has been distributed to and has had a significant
      economic impact on wide geographical areas, including Africa and South America.
      Our previous study on Trypanosoma brucei brucei showed that the trypanosome
      alternative oxidase (TAO, TbAOX) is a promising target of chemotherapy. For this
      reason, we also have cloned the T vivax AOX (TvAOX) gene and characterized the
      recombinant enzyme. The deduced amino acid sequence (328 a.a.) of TvAOX shares
      76% identity with TbAOX and contains the diiron-coordination motifs (-E-, -EXXH-)
      that are conserved among AOXs. The Km of recombinant TvAOX (rTvAOX) expressed in
      Escherichia coli for ubiquinol (87.0 +/- 0.54 microM) was significantly lower
      than the value for recombinant TbAOX (rTbAOX) (714 +/- 4.5 microM). Ascofuranone,
      the most potent inhibitor of TbAOX, was a competitive inhibitor of rTvAOX with a
      Ki value (0.40 +/- 0.00 nM) significantly lower than that for rTbAOX (1.29 +/-
      0.00 nM). The non-cyclic transmission ability of T. vivax and the in vivo
      chemotherapeutic efficacy of ascofuranone against T. vivax and T. b. brucei
      infection are discussed in terms of these Km and Ki values.

PMID- 15468533
TI  - Trichomonas vaginalis: random amplified polymorphic DNA analysis of isolates from
      symptomatic and asymptomatic women in India.
AB  - Trichomonas vaginalis, the causative agent for human trichomoniasis, is a
      protozoan parasite. Trichomoniasis is the most common non-viral sexually
      transmitted disease. The infection in women may be asymptomatic or may lead to
      severe vaginitis, cervicitis and severe sequelae. Despite its high prevalence,
      the genetic variability and factors leading to symptomatic infection have been
      poorly understood. One thousand women in childbearing age group were screened for
      the presence of T vaginalis. Thirty-eight women were found positive for T
      vaginalis and out of these 22 (57.9%) were having symptomatic infection and 16
      (42%) were asymptomatic. Fresh isolates from 15 symptomatic and 15 asymptomatic
      women were axenised and subjected to random amplified polymorphic DNA (RAPD)
      analysis with the use of five different random primers (OPD 1-OPD 5). The
      isolates with similar banding pattern were assigned as a single type. OPD 3
      indicated least (nine types) while OPD 4 indicated highest typing (18 types)
      ability. Phylogenetic analysis using RAPD distance software indicated two
      distinct lineages; upper branch consisting of only seven symptomatic isolates
      while lower branch consisting of all the 15 asymptomatic isolates the other eight
      symptomatic isolates were recorded in separate cluster. The study indicated that
      RAPD technique might be helpful to delineate the pathogenic mechanism(s) for its
      virulence; however, further studies on large number of isolates are desired to
      elucidate the findings.

PMID- 15468534
TI  - Cross-reactions with Ascaris suum antigens of sera from mice infected with A.
      suum, Toxocara canis, and Angiostrongylus cantonensis.
AB  - Ascaris suum larval excretory-secretory (AsES) antigen and larval (AsLA) as well
      as adult somatic antigen (AsAA) which were thought to be possibly helpful in the
      diagnosis of visceral larva migrans (VLM) due to A. suum infection were
      investigated in the present study. Serum taken from mice orally inoculated with
      approximately 250 embryonated eggs of A. suum or Toxocara canis, or 40 third
      stage larvae of Angiostrongylus cantonensis were assessed by enzyme-linked
      immunosorbent assay (ELISA) using the AsES antigen, AsLA or AsAA at 1, 2, 3, 4, 6
      and 8 weeks post infection (WPI). The titer of serum IgG from mice infected with
      A. suum increased from 1 WPI and a peak at 4 WPI was observed when it reached
      approximately three times the level of uninfected control mice. Thereafter, it
      decreased gradually but remained high as found from 6 to 8 WPI. No cross
      reactions of heterologous serum IgG against AsES antigen was observed, whereas
      heterologous serum IgM exhibited significant cross-reactions to AsES antigen.
      Cross-reactivities to AsLA and AsAA by heterologous serum IgG as well as IgM
      antibodies were also observed in the trial. Altogether, the AsES antigen
      apparently seemed to be superior to the other two somatic antigens when used in
      the diagnosis of A. suum-induced VLM with serum IgG as tested by ELISA. Moreover,
      it was the first report to test the possibly antigenic cross-reactivity between
      A. suum and A. cantonensis.

PMID- 15468535
TI  - National Museum of Dentistry exhibit comes to California.

PMID- 15468536
TI  - Mercury in our environment.
AB  - Mercury is a very useful metallic element that, while not particularly abundant
      in nature, can play an important role in the overall health of humans and
      animals. This article discusses the benefits and toxicological consequences of
      society's use of mercury. It also will focus upon the mining, processing, and
      uses of mercury in the United States, and then highlight the amounts of mercury
      that are released as wastes. Along the way, three important questions are
      addressed: How much mercury is released by human activities and by natural
      events? Do these releases pose a risk either to humans or to the environment in
      general? How does this information apply to dentistry?

PMID- 15468537
TI  - Cost-effectiveness of removing amalgam from dental wastewater.
AB  - Mercury in the form of amalgam is commonly introduced into dental wastewater as a
      result of amalgam placements and removals. Dental wastewater is primarily
      discharged to municipal sewers that convey industrial and residential wastewater
      to publicly owned treatment works (POTWs) for treatment prior to discharge to
      surface waters. In some localities, the sewage sludge generated by POTWs from the
      treatment of wastewater is incinerated, resulting in the emission of mercury to
      the atmosphere. Some of the mercury emitted from the incinerators is deposited
      locally or regionally and will enter surface waters. An assessment was conducted
      of the use of mercury in amalgam in California and the discharge of that mercury
      from dental facilities to surface waters via the effluent from POTWs and air
      emissions from sewage sludge incinerators (SSIs). The annual use of mercury in
      amalgam placements conducted in California was estimated to be approximately 2.5
      tons. The annual discharge of mercury in the form of amalgam from dental
      facilities to POTWs as a result of amalgam placements and removals was estimated
      as approximately one ton. The discharge of mercury to surface waters in
      California via POTW effluents and SSI emissions was estimated to total
      approximately 163 pounds. A cost-effectiveness analysis determined that the
      annual cost to the California dental industry to reduce mercury discharges to
      surface waters through the use of amalgam separators would range from 130,000
      dollars to 280,000 dollars per pound.

PMID- 15468538
TI  - Understanding the mercury reduction issue: the impact of mercury on the
      environment and human health.
AB  - Mercury has been used in both medicine and dentistry for centuries. Recent media
      attention regarding the increased levels of mercury in dietary fish, high levels
      of mercury in air emissions, and conjecture that certain diseases may be caused
      by mercury exposure has increased public awareness of the potential adverse
      health effects of high doses of mercury. Dentistry has been criticized for its
      continued use of mercury in dental amalgam for both public health and
      environmental reasons. To address these concerns, dental professionals should
      understand the impact of the various levels and types of mercury on the
      environment and human health. Mercury is unique in its ability to form amalgams
      with other metals. Dental amalgam--consisting of silver, copper, tin, and mercury
      -has been used as a safe, stable, and cost-effective restorative material for
      more than 150 years. As a result of this use, the dental profession has been
      confronted by the public on two separate health issues concerning the mercury
      content in amalgam. The first issue is whether the mercury amalgamated with the
      various metals to create dental restorations poses a health issue for patients.
      The second is whether the scraps associated with amalgam placement and the
      removal of amalgam restorations poses environmental hazards which may eventually
      have an impact on human health. Despite the lack of scientific evidence for such
      hazards, there is growing pressure for the dental profession to address these
      health issues. In this article, the toxicology of mercury will be reviewed and
      the impact of amalgam on health and the environment will be examined.

PMID- 15468539
TI  - Dental amalgam: regulating its use and disposal.
AB  - Although dental amalgam has been a restorative material for more than 150 years,
      government regulation of its use and disposal came much later with the creation
      of new federal laws and agencies. None of the federal laws regulating dental
      amalgam today were written specifically to regulate amalgam. Instead, these new
      laws and agencies were created to address broad public safety concerns, where
      little or no regulation existed before, in the areas of medical devices and drugs
      and environmental pollution. It is the interpretation and implementation of
      environmental laws that recently have had the greatest impact on dental
      practices.

PMID- 15468540
TI  - The use of CDA best management practices and amalgam separators to improve the
      management of dental wastewater.
AB  - Concerns over the persistence and effects of mercury in the environment,
      particularly in wastewater, have increased significantly over the past decade.
      Because mercury is a component of dental amalgam, comprising about 50 percent of
      amalgam among other metals, in recent years the concern has affected dental
      practices and even educational curricula in the dental schools. While numbers
      vary widely from area to area, on average, it is estimated dentistry contributes
      less than 1 percent of the mercury generated from human activity to the
      environment. Despite dentistry's low contribution to the environmental mercury
      load, organized dentistry's position is that dentistry's role as a public health
      profession includes environmental stewardship, as well as patient safety, and
      that dental professionals must act responsibly by taking steps to prevent amalgam
      waste or any potentially harmful materials from entering the environment, no
      matter how small the amount. In support of this belief, both the California
      Dental Association and the American Dental Association have developed
      recommendations for best practice that dental offices should follow when handling
      dental amalgam waste. Many dental schools and auxiliary programs have shown their
      commitment to minimizing detrimental effects to the environment, evidenced by the
      fact that most, if not all, have incorporated safe work practices including
      mercury hygiene procedures as part of clinical coursework. Some local
      jurisdictions hardest hit by the effects of mercury in wastewater have gone even
      further to recommend, or even require, the installation of amalgam separators in
      dental offices. This article will describe the history of BMPs and amalgam
      separators usage in California, and examine the practical aspects of their usage
      in reducing the discharge of dental amalgam into waste streams.

PMID- 15468542
TI  - Are there acceptable alternatives to amalgam?
AB  - Amalgam has been the material of choice for restoring posterior teeth for more
      than 100 years. The past 25 years have witnessed significant advances in
      restorative materials themselves and in the bonding systems for retaining a
      restoration in the prepared tooth. As a result, there has been a shift toward
      resin composite materials during this same period because of concerns about the
      esthetics and biocompatibility of dental amalgam. In addition, other materials
      such as glass ionomer cements, ceramic inlays and onlays, and gold alloys have
      been used as alternatives to amalgam. This article will review recent studies on
      the longevity and biocompatibility of these alternatives to dental amalgam.

PMID- 15468541
TI  - The effect of amalgam separators on mercury loading to wastewater treatment
      plants.
AB  - Mercury (Hg) release from dental offices has become an acute issue for the dental
      profession and has resulted in efforts by regulators to mandate both the use of
      Best Management Practices (BMPs) as well as the installation of amalgam
      separators. Concern has been expressed by some regarding the efficacy of amalgam
      separators in reducing the Hg loads to wastewater treatment plants (WWTPs). Data
      from several Publicly Owned Treatment Works (POTWs) serving areas with installed
      bases of separators suggest these devices can substantially reduce Hg burdens to
      WWTPs. The data consists of Hg levels in sewer sludge (biosolids) and in some
      cases includes Hg concentrations in WWTP influent and effluent. Data comes from
      various geographical locations, and suggest separators can have a positive effect
      in reducing the amount of Hg reaching WWTPs.

PMID- 15468543
TI  - The wonder years.

PMID- 15468544
TI  - [Anesthetic management of thoracoscopic surgeries].

PMID- 15468545
TI  - [Invasion-free respiratory monitoring in thoracal surgery of oncology patients].
AB  - The results of intraoperative monitoring in thoracal surgery of 375 oncology
      patients with lung cancer were analyzed. The dynamic parameters of ventilation
      and blood gas composition were investigated in patients with uncomplicated
      anesthetic management and with complicated adequate ventilation. The diagnostic
      value of the above parameters is defined for optimizing the respiratory support
      in surgery for lung cancer.

PMID- 15468546
TI  - [A risk of myocardial ischemia and the nature of infusion-transfusion therapy in
      scheduled surgical treatment of infrarenal aneurisms of the aorta].
AB  - The authors analyzed effects produced by different variations of the infusion
      transfusion therapy on the risk of cardiovascular complications that can develop
      in the scheduled surgical treatment of the aorta abdominal part. The patients
      were randomized in 2 groups. Intraoperative hemodilution was made in group-1
      patients (n = 50) before aorta clipping. Hemodynamics was stabilized by colloids
      and crystacolloids during clip removal; donor packed red blood cells were used at
      the hemoglobin level below 80 g/l. Group 2 comprised 66 patients for whom
      autoblood was prepared preoperatively. The infusion volume was limited before
      aorta clipping; blood losses were compensated for by autoblood and
      autoerythrocytes collected from surgical blood by "Cell Saver". The below results
      were obtained on the basis of conducted research: preventive infusion load
      aggravates, before aorta clipping, the risk of cardiac complications. Maintenance
      of Hb below the level of 90 g/l is accompanied by an impaired transport of oxygen
      to tissues; it speeds up the heart beat and provokes an increased cardiac need in
      oxygen, which enhances the risk of myocardium ischemia. Preparation of autoblood
      and hardware-based reinfusion of autoerythrocytes provide for an adequate
      compensation of blood losses and diminish the risk of cardiac complications in
      the scheduled surgical treatment of infrarenal aneurisms of the aorta.

PMID- 15468547
TI  - [Aprotinin in the correction of the hemodynamic syndrome of systemic inflammatory
      response in surgeries with extracorporeal circulation].
AB  - Seventy-three patients with ischemic heart disease (IHD), who underwent coronary
      artery bypass grafting with artificial circulation (AC), were examined within a
      prospective randomized study. The patients were randomized between three groups.
      The group-1 patients were administered trasilol (T) according to the below
      scheme: 1 mln KIU from patient's admission to the surgery room to the time the
      skin incision is made plus 2 mln KIU from the moment the surgical approach is
      preformed to the beginning of AC. KIU was added to the artificial circulation
      apparatus (ACA) when it was initially filled (total T dose of 6 min KIU). T was
      administered in the group-2 patients similarly to the scheme used in group 1;
      however, it was not added to the ACA (total T dose of 3 mln KIU). And T was not
      used at all in the group-3 patients. The dose of mezatone administered at the AC
      stage was reliably higher in groups 3 and 4 versus group 1 (p < 0.05 and p < 0.1,
      respectively). Doses of mezatone that were used for the vasopressin management
      did not differ significantly between the groups after surgery. A statistically
      more significant increase of stroke index (deltaSI) and a decrease of general
      peripheral vascular resistance (GPVR--deltaGPVR) were registered in 12 hours
      after surgery in group 3 versus group 1, p < 0.05 and p < 0.01, respectively. The
      negative deltaGPRV was also more pronounced versus the parameters observed in
      group 1 and 2 (p < 0.01 and p < 0.02, respectively). Therefore, T, when used at 6
      mln KIU in AC, provides for a smaller-scope vasopressin management in AC. And,
      when it is used before AC at 3 mln KIU, T dose not diminish the dose of
      vasopressin management in AC. The intraoperative use of T (6 or 3 mln KIU)
      arrests a pronounced decreased postoperative deltaGPRVR and an increased
      postoperative CI irrespective of a dose.

PMID- 15468548
TI  - [General anesthesia tools in endovascular surgery of the conductive heart
      system].
AB  - The anesthetic management course was analyzed in 224 patients who underwent
      nonvascular surgeries on the conductive heart system. Analgesic and anti-stress
      techniques, which do not affect the intracardial conductivity and ensure the
      successful outcome of surgery with spontaneous or auxiliary ALV, were designed on
      the basis of research. The above schemes were introduced in practice with their
      efficiency being confirmed. They are based on a balanced use of the new
      generation non-steroid anti-inflammatory drugs, like Xephocam, bezodiazepines and
      fentanyl (when used at subnarcotic doses that do not affect the intracardial
      conductivity). The main analgesic component of lornoxycam was sufficient when
      used at a dose of 0.1 mg/kg and at a total dose of equal to or below 16 mg.

PMID- 15468549
TI  - [Correction of temperature homeostasis and microcirculation under the stress
      protection anesthesia in hip replacement].
AB  - Prolonged epidural anesthesia belongs to the most effective anesthetic management
      schemes in total hip replacement. However, its use is related with compensatory
      stress-induced vasoconstriction resulting in an impaired vasoconstriction
      registered above the block level. It entails, in its turn, an impaired
      thermoregulation (hypothermia, postoperative muscle trembling), a reduced renal
      blood flow with diminished diuresis and metabolic lactate-acidosis. The
      preoperative preparation with daralgin (15 microg/kg, 3 intramuscular injections
      per day for 2-3 days) with its subsequent intraoperative infusion (30 microg/h)
      made concurrently with premedication by clofelin (1.5 microg/kg) arrest the above
      hemostasis impairments. Finally, the ability of stress-protection drugs to
      diminish the rate of postoperative fever and muscle trembling was registered.

PMID- 15468550
TI  - [Anesthetic management of patients in hip replacement].
AB  - The results of an efficiency study of the antinoceptive protection and of
      determination of an adaptation-reaction type in patients after total hip
      replacement with total intravenous or subarachnoid anesthesia and with
      spontaneous breathing are analyzed in the paper.

PMID- 15468551
TI  - [Chemical lumbar sympathectomy in patients with chronic ischemia of the lower
      extremities].
AB  - The efficiency of lumbar chemical sympathectomy made within the complex therapy
      for ischemic pain in the lower extremities was analyzed versus lumbar
      sympathectomy, made surgically, in 84 male and female patients aged 33-84. The
      below parameters were studied: the dynamics of painless-walking distance in
      patients with ischemia, stages IIa and IIb, and rest-pain intensity in patients
      with ischemia, stages III and IV, according to Fontaine. The regional
      hemodynamics was registered in all patients by Duplex scanning of lower
      extremities vessels before manipulation and on days 5 and 10 after sympathectomy
      performed by chemical and surgical techniques. An increased distance of painless
      walking, reduced intensity of rest pain and better parameters of regional
      hemodynamics were observed in the study and control groups; they were of the
      unidirectional nature. Thus, sympathectomy, made by the chemical technique, is
      not inferior by its efficiency to surgical lumber sympathectomy.

PMID- 15468552
TI  - [Surgical stress: clinical-and-laboratory parallels under activation of the
      natural stress-limiting systems].
AB  - Three hundred and eighty-seven patients, who were operated on the scheduled basis
      for different surgical pathologies, were examined. The purpose of the case study
      was definition of the clinical-and-laboratory parallels related with
      pronouncement of surgical stress in an advanced variation of neuroleptanalgesia.

PMID- 15468553
TI  - [Multimodal antinociceptive management of patients with ileus in surgery].
AB  - Acute ileus has been for years a topical problem in abdominal surgery. Successful
      surgical treatment with the pathology depends not only on a surgical scheme but
      also on the efficiency of anesthetic management. The purpose of the present case
      study was to investigate issues related with appropriate anesthesia for elderly
      and senile patients in ileus surgery. General analgesia with sodium oxibutiratis,
      ketamine and phentanil, when combined with epidural anesthesia with ropivaciane,
      provides for an adequate anesthetic management of elderly and senile patients in
      ileus surgery.

PMID- 15468554
TI  - [Total intravenous anesthesia with ketamine and the condition of the higher
      psychic function in the early and remote postoperative periods].
AB  - Influence of total intravenous anesthesia with ketamine on the higher psychic
      function was studied, immediately after surgery and in the remote postoperative
      period, in 143 patients with different typological properties of the nervous
      system after a scheduled surgery--supravaginal uterectomy in fibromyoma of the
      uterine body. The authors defined 6 groups of patients with different typological
      properties of the nervous system. Persistent impairment of the higher nervous
      functions were established, immediately after surgery and in the remote
      postoperative period, in patients with a weak nervous system, biased nervous
      balance towards excitation, and with lability of nervous processes. Total
      intravenous anesthesia with ketamine, when used in patients with the robust
      nervous system, biased nervous balance towards excitation, and with lability of
      nervous processes, caused changes in the higher nervous functions and an
      intensified level of nervous-and-psychic loads, which were unstable and were
      arrested by the 30th postoperative day. The use of such anesthetic scheme was
      found to be inadvisable in the above groups of patients. The described
      impairments were not registered when total intravenous anesthesia was used in
      patients with a balanced nervous system irrespective of its type, a biased
      nervous balance towards inhibition and with inertness of nervous processes. The
      above anesthetic management is acceptable for such patients.

PMID- 15468555
TI  - [Diagnostics and correction of thrombohemorrhagic impairments in patients with
      purulent-septic complications in obstetrics and gynecology].
AB  - The clinical course of thrombohemorrhagic complications was studied in 56
      patients, aged 18 to 38, with sepsis, which developed due to obstetric and
      gynecologic processes on days 1, 3, 5, 7 and 10 after surgery. The patients were
      treated, 1999-2003, at the obstetric intensive-care and consultation center, MUZA
      Maternity Hospital No. 1, Krasnoyarsk. The coagulation, anti-coagulation and
      fibrinolytic chains of the coagulation cascade and vascular-thrombotic hemostasis
      were dynamically evaluated. Thrombohemorrhagic complications in severe sepsis and
      septic shock manifested themselves as hypercoagulation stage in 52% of
      observations. The hemostasis correction does not only require the elimination of
      changes in the hemocoagulation system but also the intensive care of the present
      systemic dysfunctions.

PMID- 15468556
TI  - [Differential choice of intensive care in abdominal sepsis].
AB  - The purpose of the case study was substantiation of a differential intensive care
      in abdominal sepsis with respect to its clinical-and-pathogenetic variations.
      Retro- and prospective clinical-and-biochemical parameters were investigated in
      60 patients with disseminated peritonitis and abdominal sepsis. The patients were
      shared between 3 groups with respect to their clinical-and-laboratory findings.
      Clinical-and-pathogenetic types were defined for the clinical course of abdominal
      sepsis (AS). It was found as necessary to add enteral detoxication to the
      combined intensive care scheme in type 1 AS. A single-stage intravenous perftoran
      infusion plus enteral detoxication are required in type 2 AS. And in type 3 AS,
      the therapeutic scheme should be expanded through intravenous infusion of
      perftoran with subsequent enteral detoxication.

PMID- 15468557
TI  - [Diastolic malfunction in sepsis and septic shock].
AB  - The onset and development of cardiac insufficiency is associated with diverse
      pathophysiological mechanisms with attention being focused recently on studying
      the significance of "proinflammatory" cytokines, primarily, of TNFalpha. Fifty
      nines patients (age--18-24, body weight--54-76) with sepsis (19 persons, group
      1), severe sepsis (20 persons, group 2) and with septic shock (20 persons, group
      3) were examined. The mechanic function of the left cardiac ventricle and
      hemodynamic parameters were evaluated by a routine scheme in the modes of 1D (M
      echo-cardiography) and sector scanning (2D echo-cardiography) at the SIM-5000
      device (Italy). The central hemodynamic indices were investigated by integral
      tetrapolar rheography according to Tishchenko. The results denote a big
      significance of diastolic malfunction of the left cardiac ventricle or "rigid"
      myocardium in shaping of myocardial malfunction as observed in sepsis and septic
      shock.

PMID- 15468558
TI  - [Activated C protein in severe sepsis].

PMID- 15468559
TI  - [Evaluation of the function of the hematoencephalic barrier in victims with
      craniocerebral trauma in critical state].
AB  - Estimates of the relative-entry coefficient, molecular profile of the
      cerebrospinal fluid and of the molecular blood profile based on the comparison of
      concentrations of proteins with different physical-and-chemical properties enable
      an evaluation of the function of the hematoencephalic barrier in victims with
      craniocerebral trauma in critical state. It was possible to state, with such
      approach in use, that the regulatory and protective functions of the
      hematoencephalic barrier were changing differently in favorable and unfavorable
      trauma outcomes, which must be duly considered in choosing a treatment tactics
      for the above category of victims.

PMID- 15468560
TI  - [Neuroprotection by ketamine and dopamine-saving drugs in severe craniocerebral
      trauma at exacerbation and in the treatment of apallic syndrome].

PMID- 15468561
TI  - [An algorithm of respiratory management in the complex treatment and prevention
      of acute pulmonary lesions in patients with impairments of the central nervous
      system].
AB  - The authors elaborated an algorithm of respiratory management (RM) based on the
      correlation of RM parameters with the actual and proper thoracopulmonary
      compliance (C). The algorithm was tested on 42 patients with affections of the
      central nervous system (CNS) due to severe craniocerebral trauma, spinal trauma,
      cerebral stroke and multitrauma. Thirty-nine case-matching patients where in the
      control group--the routine RM algorithm was used for them. Mean pressure in the
      respiratory paths (Pmean, C, PaO2/FiO2 and rSO2 readings by the Glasgow coma
      scale, cerebral perfusion pressure, and consumption of sedatives, muscle
      relaxants and vasopressins as well as frequency rate of acute pulmonary lesions
      (APL) were registered. The RM algorithm provided for a more effective prevention
      and treatment of APL versus the routine RM--it cut, 3-fold, the remote APL. With
      the above RM algorithm, the need in sedatives, muscle relaxants and vasopressins
      went down from day 2. Positive trends in the neurological status as well as
      normalized rSO2 were observed earlier versus the controls. Finally, its use
      ensured a more favorable treatment outcome.

PMID- 15468562
TI  - [An analysis of using the graphic monitoring of ventilation for an optimal choice
      of respiratory management parameters in patients with acute respiratory distress
      syndrome].
AB  - The potentialities of graphic ventilation monitoring (graphic monitor "Servo
      Screen 390", Siemens Elema, Sweden) were analyzed for optimizing the respiratory
      management parameters in 48 obstetric and gynecology patients with acute
      respiratory distress syndrome (ARDS). The ventilation loops and curves, ALV
      parameters, mechanical lung properties, gas blood composition and gas indices
      were dynamically evaluated during examination stages. The graphic ventilation
      monitoring, when used for respiratory management in patients with ARDS, provides
      for optimizing, in the real time mode, the PEEP and Vt levels, which is in line
      with the AVL "safety" concept.

PMID- 15468563
TI  - [Early nutrition support for intestinal insufficiency syndrome in spine surgery].
AB  - Paresis of the gastrointestinal tract resulting in the intestinal insufficiency
      syndrome (IIS) is a postoperative risk factor in spinal surgery. One hundred and
      twenty patients with fractures at L1-L2 spine level, isthmic spondylolisthesis,
      osteochondrosis and with sever neurological symptoms were examined and treated.
      The intestinal motor-evacuation malfunction, hypermetabolism, microbial
      translocation and immunity impairments are observed in IIS. Early nutritional
      support is indicated for the IIS prevention and treatment. Enteral feeding with
      new balanced mixtures containing fibers is effective.

PMID- 15468564
TI  - [Choosing of scale for determining the condition severity in patients with acute
      blood loss].
AB  - Inefficiency of therapy for massive blood losses and hemorrhagic shock can be
      partially explained by inability to identify, as early as possible, the risk
      groups. The purpose of our case study was to investigate the significance of
      diagnostic systems in evaluating the condition severity of patients. One hundred
      and nine male patients (mean age 41.6 +/- 8.1) were examined within the
      randomized prospective study. Examinations were made at admission and in 24 and
      72 hours after injury according to the protocols of condition severity evaluation
      -APACHE-II, III (Acute physiology and chronic health condition) and SAPS
      (Simplified Acute Physiology Score). The scales used in the study are described
      by a high reliability degree in differentiating the severity conditions of
      patients (p < 0.0001). The direct linear relation was observed in all cases
      between the severity condition of patients and the lethality rate (correlation
      factor r(X,Y) > 0.89). The highest specificity was noted for the APACHE-III
      diagnostic system.

PMID- 15468565
TI  - [Some pathophysiological aspects of hyperthermic pharmacotherapy and its clinical
      use].
AB  - The use of artificially induced general controllable hyperthermia (GCH) of high
      degree is acknowledged as the 21st century intensive technology; it is used in
      the treatment of diseases and conditions that can be hardly cured by routine
      methods. Pathogenetic pharmacotherapy was made use of to enhance, purposefully,
      the GCH efficiency. The suggested concept, i.e. reproduction of the most
      efficient use of positive effects from high temperature and thermally mediated
      effects of pharmacotherapy, was named as "hyperthermic pharmacotherapy". The
      controllable maintenance of the "biological zero" phenomenon in the brain
      (registered by EEG) at 42-44 degrees C is the safety criterion of high-level GCH.
      The described intensive-care technique can be referred to as promising
      considering the modern anesthesiological-management potentialities related with
      GCH safety.

PMID- 15468566
TI  - [Filtration and sorption of liquor].

PMID- 15468567
TI  - [Alcohol drinking patterns in dental students].

PMID- 15468568
TI  - [About the vaccines against human papilloma virus].

PMID- 15468569
TI  - [Health differences between male and female migrant agricultural workers in
      Sinaloa, Mexico].
AB  - OBJECTIVE: To assess the differences in the prevalence of muscarinic and
      nicotinic type symptoms and the level of erythrocytic cholinesterase, prior to
      pesticide exposure, in male and female migrant agricultural workers. MATERIAL AND
      METHODS: A cross-sectional study was carried out in 2001 in Sinaloa State,
      Mexico, among 488 migrant workers. A questionnaire was applied and erythrocytic
      cholinesterase levels were measured before the beginning of the agricultural
      season. The differences by sex were compared using the "t" test for continuous
      variables and chi2 test for categorical variables. Prevalence odds ratios were
      also estimated. Statistical significance was assessed using p-values <0.05 and
      95% confidence intervals. RESULTS: Significant differences were found by age,
      migration type, place of origin, education, and migration time (p=0.000). Women
      were six times more likely to have anemia and asthma, twice more likely to have
      parasites and respiratory and gastrointestinal diseases and 38% more likely to
      suffer from heart disease. They were also at greater prevalence in thirteen of
      nineteen investigated symptoms. The average cholinesterase level was within
      normal limits (4.22 U/ml+/-0.77) and it was similar to the levels reported using
      the Magnotti method. CONCLUSIONS: The prevalence of symptoms, illnesses and
      cholinesterase levels found in this study may serve as baseline values for future
      comparisons of the health effects of pesticide exposure. The English version of
      this paper is available at: http://www.insp.mx/salud/index.html.

PMID- 15468570
TI  - [Institutional factors contributing to the utilization of breast clinical
      examination].
AB  - OBJECTIVE: To identify factors associated with utilization of breast clinical
      examination (BCE) and their relationship with institutional medical practice.
      MATERIAL AND METHODS: This is a qualitative study conducted between 1996 and 1997
      in medical units of Instituto Mexicano del Seguro Social (Mexican Institute of
      Social Security) and Secretaria de Salud (Ministry of Health). Eight focus groups
      were included: four groups of female users and four groups of health
      professionals; in total, 47 users and 29 physicians and nurses participated.
      Interpretations of information were based on the organizational ability to
      respond to the user's expectations, "ability/knowledge" within the organization
      and the institutional medical practice, at the light of the Grounded Theory.
      RESULTS: Service demand was conditioned on the perception of poor quality of
      care, lack of trust in physicians, and organizational aspects. When providing
      care, male physicians were not interested and felt uneasy about performing the
      BCE. Female physicians seemed more interested and were well accepted by users.
      CONCLUSIONS: Psychological, cultural, social, and institutional barriers exist in
      the access and utilization of BCE. Identifying these barriers and their origins
      could support the development of actions to improve the physician-patient
      relationship. The English version of this paper is available at:
      http://www.insp.mx/salud/index.html.

PMID- 15468571
TI  - [Towards a Mexican normative standard for measurement of the short format 36
      health-related quality of life instrument].
AB  - OBJECTIVE: To present the results of the application of the short format 36
      instrument (SF-36) in the Mexican states of Sonora and Oaxaca. The levels of
      quality of life were compared with those from Canada and the United States.
      MATERIAL AND METHODS: The data were obtained using a survey on health service
      access, usage, and quality. The SF-36 is composed of 36 questions, which
      represent eight different domains on the health-related quality of life. These
      domains are used to estimate the physical and mental components of health. Data
      analysis was performed to calculate the average scores for each domain for the
      total sample, by gender and age groups in each state. The regional differences
      were assessed by the difference of means. RESULTS: The total response was 98.5%
      of the 4200 selected households. The percent response values were similar between
      the two states. A total of 5961 subjects older than 25 years of age completed the
      questionnaire. Males scored higher than females in all domains and in both
      components. Regardless of sex, the highest variation was observed in adults up to
      64 years of age mainly in three domains: overall health, social function, and
      mental health; in the 65-74 year age group occurred mostly in social function and
      mental health; and in adults older than 75 year only in mental health. The young
      adult age group (25 to 44 years) showed variation in a greater number of domains,
      while women exhibited more variation in the "extreme" age groups, 25 to 34 years
      and 75 years and older. The mean scores in our sample were higher than those
      found in Canada and the United States in five domains and in the two summary
      components. Canada showed higher scores in the other three domains (overall
      health, social function, and mental health). CONCLUSIONS: SF-36 data are not
      available at the national level; hence, the authors recommend that their study
      results may serve as the normative reference for SF-36 in Mexico. Researchers
      using the SF-36 could compare their results with our reference, adjusted by
      gender and age in population-based studies. Considering that the study regions
      have contrasting social and economic characteristics, the data from the more
      developed state, Sonora, may be used as the normative standard. Data from Oaxaca
      would be used as the reference for less-developed states. The English version of
      this paper is available at: http://www.insp.mx/salud/index.html.

PMID- 15468572
TI  - [Cost of mother-child care in Morelos State].
AB  - OBJECTIVE: To compare the cost of maternal and child health care (current model)
      to that of the WHO Mother-Baby Package if it were implemented. MATERIAL AND
      METHODS: A pilot cross-sectional case study was conducted in September 2001 in
      Sanitary District No. III, Morelos State, Mexico. Two rural health centers, an
      urban health center, and a general hospital, all managed by the Ministry of
      Health, were selected for the study. The Mother-Baby Package Costing Spreadsheet
      was used to estimate the total cost and cost per intervention for the current
      model and for the Mother-Baby Package model. RESULTS: The total cost of the
      Mother-Baby Package was twice the cost of the current model. Of the 18
      interventions evaluated, the highest proportion of total costs corresponded to
      antenatal care and normal delivery. Personnel costs represented more than half of
      the total costs. CONCLUSIONS: The Mother-Baby Package Costing Spreadsheet is a
      practical tool to estimate and compare costs and is useful to guide the
      distribution of financial resources allocated to maternal and child healthcare.
      However, this model has limited application unless it is adapted to the structure
      of each healthcare system. The English version of this paper is available at:
      http://www.insp.mx/salud/index.html.

PMID- 15468573
TI  - [Health institutions and physicians' self-care].
AB  - OBJECTIVE: To analyze how self-care of health workers is influenced by their
      professional training and institutional setting. MATERIAL AND METHODS: This study
      took place from March 2000 to February 2001 in a health center, a general
      hospital, and a health research institute. Qualitative in-depth interviews were
      used to collect data. Four in-depth interviews were conducted among physicians at
      the study sites: two to primary care physicians and two to secondary care
      physicians. RESULTS: Study findings show that physicians face barriers to self
      care. Secondary care physicians were particularly affected by long work journeys
      and multiemployment. The main difficulties were associated with stress,
      nutrition, rest, and recreational activities. Physicians did not regularly have
      medical check-ups and would often simply consult with their colleagues in
      "hallway checkups" when they were afflicted by an illness. The physicians
      coincided in their recommendation that the health institutions should develop
      policies, programs, guidelines, and facilities to promote self-care among health
      workers. CONCLUSIONS: Health institutions are not designed or organized to
      promote self-care among their personnel. In the case of secondary care
      physicians, the organizational structure often prevents them from engaging in
      healthy activities. The English version of this paper is available at:
      http://www.insp.mx/salud/index.html.

PMID- 15468575
TI  - [Transforming growth factor-beta as a therapeutic target].
AB  - Transforming growth factor-beta (TGF-beta) family members include TGF-beta,
      activins, and bone morphogenetic proteins (BMP). These proteins are structurally
      related cytokines secreted in diverse Metazoans. TGF-beta family members regulate
      cellular functions such as proliferation, apoptosis, differentiation, and
      migration, and play an important role in organism development. Deregulated TGF
      beta family signaling participates in various human pathologies including
      autoimmune diseases, vascular disorders, fibrotic disease, and cancer. Ligand
      induced activation of TGF-beta family receptors with intrinsic serine/threonine
      kinase activity, triggers phosphorylation of the intracellular effectors of TGF
      beta signaling, the Smads proteins. Once these proteins are activated they
      translocate into the nucleus, where they induce transcription of target genes and
      regulate cellular processes and functions. Novel therapeutic strategies are
      currently being developed to correct alterations in pathologies that involve TGF
      beta as the main mediator. The English version of this paper is available at:
      http://www.insp.mx/salud/index.html.

PMID- 15468576
TI  - [Outcome indicators, 2002. Information according to the National Health System
      Institutions (Part II)].

PMID- 15468574
TI  - [Nitazoxanide vs albendazole against intestinal parasites in a single dose and
      for three days].
AB  - OBJECTIVE: To assess the effectiveness of the usual dose of nitazoxanide
      administered for three days and as a single dose for massive eradication of
      intestinal parasites in the pediatric population, compared with single-dose
      albendazole. MATERIAL AND METHODS: A randomized clinical trial was conducted in
      three rural communities in central Mexico City between 2001 and 2003 to assess
      three possible therapy regimes in a study population of 786 children 5 to 11
      years of age, 92 of whom had a positive parasitology test result (15.1%). Group 1
      included 27 patients treated with 400 mg given as a single dose of albendazole;
      group 2 included 34 patients whose therapy consisted of a 15 mg/kg/day dose for
      three consecutive days; patients in group 3 (n=31) were administered a single 1.2
      g dose of nitazoxanide. Differences in proportions were assessed using Fisher's
      exact test. RESULTS: No statistically significant differences were found in the
      effectiveness of the three treatment regimes: 80.5% with albendazole, compared
      with the two nitazoxanide alternatives (67.6% and 71%, respectively.A higher
      prevalence of side effects was observed with nitazoxanide in the three-day
      regimen (26.5%) and as a single dose (32.2%), compared with a single dose of
      albendazole (7.4%). CONCLUSIONS: According to the evidence on effectiveness and
      side effects, the use of nitazoxanide is not justified as a massive prophylactic
      medication for intestinal parasitosis control alternative in endemic areas. In
      countries with a high prevalence of intestinal parasitosis primary prevention
      measures should be the most important strategy, together with public sanitation,
      drinking water and sewage system availability, water chlorination, and
      appropriate animal fecal waste disposal, as well as health education.

PMID- 15468577
TI  - [XV International Conference on SIDA].

PMID- 15468578
TI  - [Clopidogrel protection is not increased further by ASS!].

PMID- 15468579
TI  - [Expectations and developments in atypical antipsychotics].

PMID- 15468580
TI  - [Psychotropics and weight gain].
AB  - Weight overload and obesity became these last years a major health problem.
      However gain weight is a frequent side effect of a large number of psychotropics.
      This article proposes to discuss this potential while reviewing various
      molecules. This reveals that the atypical antipsychotics are most likely to
      induce weight gain, in particular clozapine and olanzapine. The tricyclic
      antidepressants and mirtazapine come next, with the majority of the mood
      stabilizers. The old antipsychotics seem to involve less gain of weight. The SSRI
      make lose weight in the first weeks of treatment, but induce a moderate weight
      gain on the long term.

PMID- 15468581
TI  - [Influence of physical activity on mental well-being and psychiatric disorders].
AB  - It has been shown that endurance as well as resistance training improves mental
      well-being in the athlete. In patients with psychiatric disorders, physical
      exercise diminishes clinical symptoms. Especially in patients with depression,
      endurance exercise improves mood. Physical training has to be integrated in a
      concept due to the fact the physical exercise can not replace medicinal therapy.
      It has to be postulated that improved mood is a result of increased endogenous
      opioids.

PMID- 15468582
TI  - [Fatal untoward effect of furosemide: immunocytopenic purpura and cerebral
      hemorrhage].
AB  - A 74 year old man was admitted to the hospital for purpura. The history revealed
      coronary heart disease. Bypass surgery had been performed 18 months ago.
      Furosemide had recently been prescribed for cardiac insufficiency and the patient
      had taken the drug intermittently over two weeks. Laboratory analysis showed
      severe thrombocytopenia. Despite immediate treatment with intravenous
      prednisolone and platelet transfusions the patient succumbed to cerebral
      hemorrhage. Autopsy confirmed a diffuse hemorrhagic diathesis and a cellular
      response of the bone marrow typical for an acute immune reaction. The start of
      the purpura nine to ten days after the first dose of furosemide, the exclusion of
      other possible causes for purpura and the focal proliferation of T-lymphocytes in
      the bone marrow render it highly probable, that furosemide was responsible for
      the fatal thrombocytopenia. Furosemide is discussed to have a potential for
      autoimmunological untoward effects due to its sulfonamide structure. Few case
      reports describe vasculitic and allergic phenomena. The generation of antibodies
      against thrombocytes and the depression of megakaryocytic function are thought to
      be involved. Our patient had been treated with furosemide during the bypass
      surgery 18 months before the development of purpura. A sensitization to
      furosemide probably took place at that time.

PMID- 15468583
TI  - [Status febrilis and diarrhea. A 33-year-old auto mechanic and head of the
      family].

PMID- 15468584
TI  - [Therapeutic exotic beauty].

PMID- 15468585
TI  - Health care, the constitutional right.

PMID- 15468586
TI  - From watchdog to 'lap dog': JCAHO deficiences cited by GAO, but solution elusive.

PMID- 15468587
TI  - Massachusetts safe staffing: time runs out for bill this year but final hurdle on
      horizon.

PMID- 15468588
TI  - Medi-scare saves Liberals in Canada.

PMID- 15468589
TI  - The professor is out: lack of qualified educators--nursing's newest threat.

PMID- 15468590
TI  - The retention dilemma: mentoring program helps young RNs deal with reality.

PMID- 15468591
TI  - The RN footsoldier.

PMID- 15468592
TI  - Major candidates dodge health care solution.

PMID- 15468593
TI  - A milestone year for gene therapy goes unnoticed.

PMID- 15468594
TI  - AAV vectors for gene correction.
AB  - Permanent correction of genetic mutations is the ultimate goal in the treatment
      of inherited disorders. Although gene therapy protocols have proven successful in
      several clinical trials that focused on monogenetic diseases, alternative
      approaches have become the subject of growing interest since two cases of
      insertional mutagenesis were reported in one of these trials. Gene correction is
      an alternative technology that aims to repair a mutated gene rather than
      complement the mutation by adding a wild-type copy of the affected gene. This
      review focuses on viral approaches to gene correction, especially the use of
      vectors based on adeno-associated viruses. The pitfalls and prospects, as well as
      the steps needed to improve and advance the technology for clinical applications,
      are discussed.

PMID- 15468595
TI  - Vectors for RNA interference.
AB  - Introduction of double-stranded RNA into cells causes gene silencing in a
      sequence-specific manner, involving the coordinated activity of enzymes such as
      Dicer and RNA-induced silencing complex. Several groups have recently
      demonstrated that this phenomenon of RNA interference (RNAi) occurs in mammalian
      cells when small interfering (si)RNAs are used, and have developed vector-based
      siRNA expression systems that can induce RNAi in living cells. These vector
      systems use polymerase III promoters, such as U6 or H1, and are classified into
      two groups based on the form of expressed RNA, tandem or hairpin. This review
      describes the basis for, and methodology of siRNA expression vectors for
      mammalian cells.

PMID- 15468596
TI  - HIV-1-specific RNA interference.
AB  - The preclinical development of RNA interference (RNAi) as a novel therapeutic
      agent for HIV-1 infection is reviewed. RNAi refers to the sequence-specific
      degradation of RNA that follows the cellular introduction of homologous, short
      interfering RNA (siRNA). RNAi has emerged as a powerful tool to probe the
      function of genes of known sequence in vitro and in vivo. Advances in vector
      design permit the effective expression of siRNA in human cells by transfer of
      short hairpin RNA expression cassettes. Recent investigations have described the
      ability of RNAi to decrease the replication of HIV-1 in lymphocytic cells using
      siRNA targeting viral (eg, Tat, Gag and Rev) and host (eg, CCR5 and CD4)
      proteins. Can RNAi be used as a form of genetic therapy for HIV-1 and associated
      infections? There are numerous challenges associated with converting RNAi from a
      laboratory technique to an antiviral therapeutic. Recent research on the cellular
      delivery, antiviral durability and gene-silencing specificity of HIV-1-specific
      RNAi is reviewed.

PMID- 15468597
TI  - Targeted gene transfer in heart failure: implications for novel gene
      identification.
AB  - Heart failure remains an intractable disease with epidemic proportions in the
      Western World. While progress in conventional treatment modalities for congestive
      heart failure is making steady and incremental gains to reduce this disease
      burden, there remains a need to explore new potentially therapeutic approaches.
      Gene therapy, for example, was initially envisioned as a treatment strategy for
      inherited monogenic disorders. It is now apparent that gene therapy has broader
      potential that also includes acquired polygenic diseases, such as heart failure.
      Advances in the understanding of the molecular basis of congestive heart failure,
      together with the evolution of increasingly efficient gene transfer technology,
      has placed congestive heart failure within reach of gene-based therapy. In
      addition, gene-based reconstitution of a normal phenotype allows us to closely
      examine the behavior of a large number of transcripts as the heart fails and is
      rescued by genetic manipulations.

PMID- 15468598
TI  - Recent developments in molecular therapeutic approaches for rheumatoid arthritis.
AB  - Rheumatoid arthritis is a debilitating systemic autoimmune disease characterized
      by chronic synovial inflammation, which results in the progressive destruction of
      diseased joints. Advances in understanding the disease pathogenesis have led to
      the clinical introduction of biological inhibitors of inflammation or articular
      destruction. However, frequency of administration, cost and systemic side effects
      have driven efforts to develop gene therapeutic transfer strategies. This article
      reviews recent progress in the application of viral and non-viral vectors to
      target therapeutic genes for in vivo delivery.

PMID- 15468599
TI  - Multicellular tumor spheroids in gene therapy and oncolytic virus therapy.
AB  - Multicellular clusters of cells, or spheroids, can be grown and sustained in
      vitro, facilitating various cancer research and treatment approaches. As
      spheroids are three-dimensional and retain many of the cell types and features
      present in the original clinical tissues, they provide an important link between
      two-dimensional cell lines and in vivo xenograft studies. With regards to gene
      therapy and replication-competent oncolytic viruses in particular, spheroids
      allow sustained viability of primary tumor cells in vitro, a requirement for
      reliable analysis of replication. Analysis of clinical samples is of paramount
      importance for preclinical evaluation of candidate anticancer agents.

PMID- 15468600
TI  - Encapsulated, genetically modified cells producing in vivo therapeutics.
AB  - The ability to implant genetically modified cells in immuno-isolating materials
      has much potential for therapeutic use. This review presents the different types
      of polymer that can be used for encapsulation of cells and the recent use of
      genetically modified, encapsulated and thus immunoprotected cells for the
      treatment of diseases in animal models and clinical trials. Some of the
      challenges faced by these technologies and potential solutions are also
      discussed.

PMID- 15468601
TI  - Gene-directed enzyme prodrug therapy: a current assessment.
AB  - Gene-directed enzyme prodrug therapy involves tumor-specific delivery of a gene
      encoding a drug-metabolizing enzyme allowing metabolism of a non-toxic prodrug to
      a toxic species directly within tumor cells. This review covers the wide range of
      enzyme-prodrug combinations currently under preclinical and clinical
      investigation. Issues of tumor specificity and enhanced cytotoxicity through
      bystander effects will be discussed.

PMID- 15468602
TI  - Technology evaluation: TroVax, Oxford BioMedica.
AB  - TroVax, a gene-based tumor vaccine that uses a poxvirus vector to deliver the
      tumor antigen gene 5T4, is under development by Oxford BioMedica for the
      potential treatment of cancer. TroVax is undergoing phase II clinical trials.

PMID- 15468603
TI  - Technology evaluation: ChimeriVax-DEN, Acambis/Aventis.
AB  - Acambis, in collaboration with Aventis Pasteur, is developing a chimeric vaccine
      based on a recombinant yellow fever vaccine for the potential prevention of
      dengue virus infection. The vaccine is undergoing phase I clinical trials.

PMID- 15468604
TI  - Technology evaluation: ABT-510, Abbott.
AB  - ABT-510 is a small peptide thrombospondin-1 mimetic angiogenesis inhibitor under
      development by Abbott Laboratories for the potential treatment of solid tumors.
      ABT-510 is undergoing phase II clinical trials.

PMID- 15468605
TI  - Association of caregiver planning with recent experiences of crisis.
AB  - In this exploratory descriptive study, two classification procedures were used to
      organize and link 479 written plans of 92 adult children caregivers pre-selected
      for recent experiences of crisis. The subjects provided nearly five hours of care
      daily to a cognitively impaired parent and composed an average of 5.21 plans for
      caregiving in the coming two weeks. Subjects reflecting a hands-on, personal
      approach to caregiver planning reported significantly lower ratings for emotional
      arousal and perceived risk for loss of health than other subjects. Subjects
      reflecting an instrumental approach to planning, in addition, composed
      significantly more abstract plans directed to concerns about personal or
      relational sense of security. Subjects composing plans reflective of their grief
      provided significantly fewer hours of parental care and composed fewer plans for
      parental care than other subjects. This information and how it was obtained can
      be used to highlight and strengthen decision-making and parental care capacities
      within the family.

PMID- 15468606
TI  - Talking the talk: a discourse analysis of mental health nurses talking about
      their practice.
AB  - Mental Health nursing exists as a discipline in the UK within the wider
      contemporary health care establishment. Throughout its history it has attempted
      to define itself in ways that differentiate mental health nursing practice from
      other health care professions and fields of nursing. However, it is not
      surprising in this climate of contemporary healthcare for individual professional
      identities to become 'lost' in the melange of interdisciplinary practice. This
      research presents a discourse analysis of individual mental health nurses'
      rhetorical constructions of their professional role(s) as they emerge in their
      talk with each other in focus group discussions. In particular, the focus in this
      paper is their discursive repertoires related to the historical legacy of mental
      health nursing and how this sits with what they consider to be a 'custodial and
      controlling' element of their role. The particular discourse analytic approach
      adopted in this study illustrates how individuals use language in a particular
      way to make justifications and explanations of mental health nursing identities.
      This analytic approach is ensconced within the domain of social psychology and
      lies at the interface of ethno-methodology and conversation analysis. It is
      concerned with structural units of discourse, beyond the level of the sentence,
      that emerge as the nurse participants engage in talking about their practice
      (Potter and Wetherell, 1987 p.53).

PMID- 15468607
TI  - "A comparison of the effectiveness of two hypnotic agents for the treatment of
      insomnia".
AB  - OBJECTIVE: To compare the effectiveness and tolerability of two hypnotic agents,
      trazadone (Desyrel) and zaleplon (Sonata) on psychiatric inpatients with
      insomnia. METHODS: Fifteen patients who were psychiatric inpatients were assigned
      openly and randomly to receive either trazodone (50-100 mg) or zaleplon (10-20
      mg) doses on an "as-needed basis" and followed throughout their hospital stay.
      Efficacy and side effect profile were subsequently assessed. CONCLUSION: This
      pilot study suggests that trazodone may be a better agent to promote longer,
      deeper subjective quality sleep for psychiatric inpatients with insomnia in terms
      of effectiveness. However, tolerability was much better with zaleplon as daytime
      residual side effects were less.

PMID- 15468608
TI  - Spasm or transformation? Advanced practice psychiatric nursing education in the
      United States.
AB  - Psychiatric nursing graduate programs are in precipitous decline in the United
      States, leading many advanced practice psychiatric nurses to question the
      viability of their field. This article examines the current crisis in advanced
      practice psychiatric nursing education in the United States by identifying core
      concerns and exploring the reasons for these concerns. Suggestions for securing
      the future of this practice area are also discussed. These suggestions include
      identifying a more clearly focused role for advanced practice psychiatric nurses,
      development of realistic educational expectations, achievement of greater
      uniformity in curricula, and the establishment of a strong and rigorous process
      of accreditation.

PMID- 15468609
TI  - Coercive treatment is a challenge for psychiatric nursing in Europe [a news item
      from Finland].

PMID- 15468610
TI  - The evolving treatment of chronic hepatitis C: where we stand a decade out.
AB  - The treatment of hepatitis C has evolved rapidly since the identification of the
      hepatitis C virus (HCV) in 1989. Since the first accepted therapy for HCV
      infection, recombinant interferon, received marketing approval a little more than
      a decade ago, it has come to be used in combination with ribavirin for improved
      rates of sustained virologic response. Recently, pegylated versions of interferon
      have been developed for use with ribavirin, offering pharmacokinetic advantages
      and further improvements in response rates over conventional interferon. This
      article briefly reviews how these evolving regimens for HCV infection have
      addressed the subtle and singular characteristics of this challenging virus.

PMID- 15468611
TI  - Initial treatment for chronic hepatitis C: current therapies and their optimal
      dosing and duration.
AB  - The main treatment goal in patients with chronic hepatitis C virus (HCV)
      infection is the prevention of progressive hepatic fibrosis by eradicating serum
      and intrahepatic virus. The current standard of care in previously untreated
      patients with chronic hepatitis C is combination therapy with pegylated
      interferon alfa and ribavirin. The duration of therapy and the dose of ribavirin
      should be determined according to the patient's HCV genotype. Adherence to the
      full dose of therapy for the prescribed treatment duration enhances the
      likelihood of sustained virologic response. Early virologic response is a good
      predictor of eventual sustained response for patients with HCV genotype 1
      infection. Despite important gains in treating chronic hepatitis C, many
      treatment challenges remain.

PMID- 15468612
TI  - Retreatment of patients who do not respond to initial therapy for chronic
      hepatitis C.
AB  - Despite improvements in the treatment of chronic hepatitis C virus (HCV)
      infection, nearly half of all patients do not respond to initial therapy.
      Retreatment of these patients with pegylated interferon and ribavirin has been
      successful in only a limited percentage of cases. Factors associated with
      sustained virologic response (SVR) following retreatment include prior treatment
      with interferon monotherapy, HCV genotype 2 or 3, a low serum HCV RNA level, and
      the absence of cirrhosis. Fewer than 6% of nonresponders who were previously
      treated with interferon and ribavirin and who have cirrhosis, genotype 1, and a
      high viral load achieve SVR following retreatment with pegylated interferon and
      ribavirin. No therapy has been shown to yield SVR in patients who do not respond
      to pegylated interferon and ribavirin. Long-term maintenance therapy with
      pegylated interferon is currently being evaluated in nonresponders with advanced
      fibrosis and cirrhosis. Its use should be considered investigational at this
      time.

PMID- 15468613
TI  - Managing the hematologic side effects of antiviral therapy for chronic hepatitis
      C: anemia, neutropenia, and thrombocytopenia.
AB  - Hematologic abnormalities such as anemia, neutropenia, and thrombocytopenia are
      common during combination therapy with pegylated (or standard) interferon and
      ribavirin for chronic hepatitis C. Ribavirin-induced hemolytic anemia is a common
      cause of dose reduction or discontinuation. Bone marrow suppression also
      contributes to the anemia and is the predominant mechanism for interferon-induced
      neutropenia and thrombocytopenia. Although dose reduction or discontinuation of
      combination therapy can reverse these abnormalities, they may reduce virologic
      response. Hematopoietic growth factors may provide a useful alternative for
      managing these hematologic side effects without reducing the optimal dose of the
      combination antiviral regimen. Treatment of anemia also may improve patients'
      health-related quality of life and their adherence to combination antiviral
      therapy. The impact of growth factors on sustained virologic response and their
      cost-effectiveness in patients with chronic hepatitis C need further assessment.

PMID- 15468615
TI  - Managing the neuropsychiatric side effects of interferon-based therapy for
      hepatitis C.
AB  - Neuropsychiatric side effects are common with interferon-based therapy for
      chronic hepatitis C, and their prompt recognition and management is essential to
      effective patient care. Depression induced by interferon has been a significant
      cause of early treatment discontinuation in clinical trials. The need to monitor
      for and treat interferon-induced depression is well established, but whether to
      use antidepressants prophylactically remains controversial. Nonetheless,
      clinicians should maintain a low threshold for antidepressant therapy. Other
      significant neuropsychiatric side effects include anxiety, hypomania or mania,
      fatigue, and cognitive dysfunction. These can be additional sources of patient
      distress during interferon therapy and require appropriate intervention through
      patient education, psychotropic medications, support, and behavioral techniques.

PMID- 15468614
TI  - The role of hematopoietic growth factors in special populations with chronic
      hepatitis C: patients with HIV coinfection, end-stage renal disease, or liver
      transplantation.
AB  - Certain populations with chronic hepatitis C face special challenges in attaining
      optimal adherence to antiviral therapy, including patients coinfected with human
      immunodeficiency virus, patients undergoing dialysis for end-stage renal disease,
      and liver transplant recipients. These patient groups may stand to gain
      particular benefit from the expanding use of hematopoietic growth factors to
      manage the cytopenic effects of antiviral therapy for hepatitis C. This article
      reviews the rationale, current evidence, and future prospects for the adjunctive
      use of growth factors in these special populations with hepatitis C.

PMID- 15468616
TI  - The role of physician extenders in managing patients with chronic hepatitis C.
AB  - The number of "physician extenders" (nurse practitioners and physician
      assistants) caring for patients with chronic hepatitis C is rising rapidly. Their
      growing role in the management of these patients promises greater efficiency in
      the delivery of care and more provider interaction with patients. This may yield
      benefits in terms of patient education and support, management of medication side
      effects, and patient adherence to treatment regimens. This article reviews the
      role of physician extenders in the management of patients with hepatitis C and
      outlines strategies for maximizing their contribution to the care of these
      patients.

PMID- 15468617
TI  - Physician attitudes and practices on providing care to individuals with
      intellectual disabilities: an exploratory study.
AB  - A dearth of literature exists regarding barriers to physicians providing medical
      care to patients with intellectual disabilities. Using an exploratory study, we
      assessed current physician practice for this population of patients. We mailed a
      17-question anonymous survey to primary care physicians (PCPs) in Connecticut.
      Results showed that many physicians care for patients with intellectual
      disabilities, but approximately 62% of physicians believed caring for this group
      to be more difficult compared to other groups. Lack of training and education
      pertaining to patients with intellectual disabilities, issues of communication,
      and interruptions in continuity of patient care affect physicians' ability to
      care for this population. Future research should establish best practices and
      examine nationwide practices in providing care to patients with intellectual
      disabilities.

PMID- 15468618
TI  - The best and worst of times: cautious optimism and the care of older adults with
      disabilities.

PMID- 15468619
TI  - Management of psychiatric issues in patients with intellectual disability.
AB  - The psychiatric treatment of people with intellectual disability and mental
      illness has progressed substantially. Not only have our interventions improved,
      the willingness and ability of psychiatrists to provide such care has grown
      enormously. Inclusion of psychiatric residents in this endeavor enhances the
      likelihood of future treatment interest by them as professionals in their own
      careers. Meaningful improvement in functional capacity and in reduction of
      symptom burden is achievable in most patients. Multiple levels of service
      delivery are adapted readily to care provision for this population when attention
      is paid to the environment of care and the education and training of staff is
      addressed. With greater attention now being paid to this population, continued
      improvement in the quality and capacity of service delivery is on the horizon.

PMID- 15468620
TI  - Creating meaningful therapy programs for people with developmental disabilities.

PMID- 15468621
TI  - Complementary and alternative medicine for older adults with intellectual
      disabilities.

PMID- 15468622
TI  - The role of the physician in early intervention for children with developmental
      disabilities.

PMID- 15468623
TI  - The physician's role in educational planning for students with developmental
      disabilities.

PMID- 15468624
TI  - Housing barriers and opportunities for persons with disabilities.

PMID- 15468625
TI  - Research issues related to individuals with intellectual disabilities.

PMID- 15468626
TI  - From a parent's perspective.

PMID- 15468627
TI  - Contrasts and challenges.

PMID- 15468628
TI  - The medical liability crisis--one physician's response.

PMID- 15468629
TI  - Sharing of information.

PMID- 15468630
TI  - Towards an ethos of value, mental health reform in the province of Ontario and
      psychosocial rehabilitation: a dialogue.
AB  - Mental health reform in Ontario is moving in the direction of community-based
      delivery of mental health services. At the same time psychosocial rehabilitation
      is emerging as a field of professional study for those who work in the community
      with individuals suffering from a mental illness. This paper offers a reflection
      on how terms popularized in mental health such as empowerment and value ought to
      communicate an existential movement rather than reified technological jargon.

PMID- 15468631
TI  - Employment, recovery, and schizophrenia: integrating health and disorder at work.
AB  - The goal of the present study was to advance theory about the processes involved
      in the recovery of work participation for individuals with schizophrenia. A
      qualitative, multiple case study design was used to study the work lives of three
      individuals. This paper focuses on the analysis of experiences of working with
      schizophrenia and, in particular, efforts to integrate disorder and health in the
      work domain.

PMID- 15468632
TI  - Development of the DPA Fidelity Scale: using fidelity to define an existing
      vocational model.
AB  - Psychiatric rehabilitation practices are often poorly defined, hindering
      implementation, research, and dissemination efforts. Documentation of adherence
      to a specific psychiatric rehabilitation approach is particularly important in
      conducting randomized controlled trials. This paper outlines steps taken to
      define and measure the Diversified Placement Approach (DPA), a well-regarded
      vocational program for people with severe mental illnesses. Details of scale
      development are described, and the scale's utility for model clarification and
      detection of experimental drift are discussed.

PMID- 15468633
TI  - Good days and bad days: the experiences of children of a parent with a
      psychiatric disability.
AB  - Twenty-two children, ages 5 to 17, described their experiences living within a
      family that included a parent with a psychiatric disability who was involved in
      community mental health agency services. The children's descriptions of parents'
      "good days" and "bad days" were captured in a secondary data analysis of a study
      that included face-to-face children's interviews. Children also discussed their
      perceptions of psychiatric disabilities and rehabilitation. Children reported
      more attention from parents on "good days." They expressed concerns about
      multiple family stressors and bias associated with psychiatric disability. They
      had little information about psychiatric disabilities and/or rehabilitation.
      Children recommended "Get help earlier."

PMID- 15468634
TI  - Tying it all together--The PASS to Success: a comprehensive look at promoting job
      retention for workers with psychiatric disabilities in a supported employment
      program.
AB  - Job initiation rates are steadily improving for people with severe and persistent
      mental illnesses. Yet, job retention rates, especially for those individuals who
      historically have had difficulty maintaining employment, continue to concern
      vocational rehabilitation professionals. In this paper, the author develops and
      refines her ideas that were presented in a previous research paper titled
      "Differences in Job Retention in a Supported Employment Program, Chinook
      Clubhouse." A more complete model, "The PASS to Success," is suggested by
      incorporating existing research with the author's revised work. Components of the
      model (Placement, Attitude, Support, Skills), can be used to predict vocational
      success and promote job retention.

PMID- 15468635
TI  - The Generic Work Behavior Questionnaire (GWBQ): assessment of core dimensions of
      generic work behavior of people with severe mental illnesses in vocational
      rehabilitation.
AB  - The purpose of this study was the development of a short self-reporting and
      supervisor-reporting questionnaire to assess generic work behavior of people with
      severe mental illnesses participating in psychiatric vocational rehabilitation.
      An 18-item generic work behavior questionnaire (GWBQ) was developed, which
      contains core dimensions derived from both supervisor scores and self-report
      scores. The factor structure of the GWBQ was replicated for both versions
      (supervisor and self reports). The GWBQ was very reliable for supervisor reports
      and moderately so for self-reports. Although self-report scores and supervisor
      scores correlated significantly, participants rated their own work behavior
      consistently higher than supervisors did.

PMID- 15468636
TI  - The importance of subjective psychotic experiences: implications on psychiatric
      rehabilitation of people with schizophrenia.
AB  - Starting with Jaspers in 1910, subjective psychotic experiences of people with
      schizophrenia became an important area in treatment and rehabilitation of people
      with schizophrenia. Nevertheless, this area of study is overshadowed by the
      statistically and diagnostically oriented DSM movement. In this article, the
      writer tries to re-visit various approaches in understanding subjective psychotic
      experiences of people with schizophrenia. It seems that subjective psychotic
      experiences represent persons' inner feelings; their spontaneous struggle in
      their process of treatment and rehabilitation. All these experiences are
      meaningful for the persons with psychiatric disabilities. In this paper, the
      writer tries to show that empathetic understanding of subjective experience can
      help individuals to re-establish a meaningful relationship with people with
      schizophrenia and motivate them to become involved in their own rehabilitation
      process.

PMID- 15468637
TI  - Conditions facilitating knowledge exchange between rehabilitation and research
      teams--a study.
AB  - This paper describes an experience in the exchange of information between
      researchers and practitioners, where conditions favorable to knowledge exchange
      were systematically documented. Conditions related to the organization proved to
      be the most determining, as did the quality and intensity of communication
      between the actors. This communication process is enhanced by characteristics
      related to practitioners and researchers. However, the well-established
      boundaries between the practitioners and the researchers, fueled by distinctive
      rules of practice, remain a major issue. Knowledge brokerage, effective reporting
      skills, and adapted, well-focused feedback could help to bring together the
      researchers and their partners.

PMID- 15468638
TI  - Prevalence and characteristics of parenting among people served by Assertive
      Community Treatment.
AB  - This study examines the prevalence and the characteristics of parenting among
      people served by Assertive Community Treatment (ACT). Four semi-rural ACT teams
      in southeastern Ontario were surveyed. The findings suggest that a significant
      minority (38%) of persons receiving ACT services are parents, although most (84%)
      do not live with their children and many rarely see their children. These
      findings are surprising considering the lack of discussion in the literature
      about parenting among recipients of ACT services. The results are discussed in
      terms of the meaning for ACT services.

PMID- 15468639
TI  - Quality of life and family functioning in caregivers of relatives with mood
      disorders.
AB  - This study examines the quality of life of caregivers of hospitalized relatives
      with mood disorders. Caregivers reported poor social, physical and emotional
      functioning. Family functioning was poor in the areas of roles, communication and
      affective involvement. It is significant that problem-solving, affective
      responsiveness and behavior control are within the normal range, indicating that
      these families do have strengths. Subjective burden but not objective burden was
      correlated with a poorer quality of life. Less than 30% of caregivers received
      help from other relatives and less than 5% sought help from outside organizations
      like NAMI, MDDA or VNA.

PMID- 15468640
TI  - The pros and cons of different warm line settings.
AB  - Of the three different ways to set up a peer-run warm line, beeper systems have
      the most advantages. Workers can take calls wherever they are, talk at length,
      and know who is calling before they call them back. In contrast, beneficial
      support amongst coworkers in an office setting gets offset by transportation
      difficulties leading to irregular hours of operation. With call forwarding, the
      convenience of working at home and easily finding substitute workers gets offset
      by time limits on calls and an inability to differentiate warm line calls from
      other calls. Such organizational differences impact the effective provision of
      peer support in these settings.

PMID- 15468641
TI  - The need to explore the prevalence and treatment of acquired brain injury among
      persons with serious and persistent mental illnesses.
AB  - This article highlights the importance of studying the prevalence and treatment
      of acquired brain injury among persons with serious and persistent mental
      illnesses. It is likely that the prevalence of acquired brain injury among
      persons with serious and persistent mental illnesses may be underreported and
      therefore, treatment may not address symptoms arising from brain injuries. This
      topic needs to be explored so that persons may participate in treatment that is
      appropriate to their neurological as well as psychiatric illnesses and so that
      the clinicians treating these persons may better understand techniques for
      addressing the needs of a person with an acquired brain injury.

PMID- 15468642
TI  - Treatment of psychiatric impairment complicated by co-occurring substance use:
      impact on rehospitalization.
AB  - This study employs available clinical data to examine the impact of a structured
      ward-based extended treatment program for the co-occurring issues of psychiatric
      impairments and substance abuse as well as a short-term variant of that program
      for acute care settings. While individuals with these co-occurring difficulties
      are often considered to be relatively refractory to treatment with inevitably
      poorer outcomes, the data from this study indicate that significantly decreased
      rehospitalization rates were realized as a result of these interventions. The
      implications of our procedures for treatment in similar settings, as well as how
      treatment in such settings can be evaluated, are discussed.

PMID- 15468643
TI  - From depths of despair to heights of recovery.
AB  - While disclosure of my personal experience with mental illness and recovery is
      not without some concern regarding its reception by others, I feel it's important
      I tell my story. This is because I wish to challenge the misunderstanding and
      stigma that surely surround mental illness. Also, I want to hold out hope to
      anyone presently struggling in the direction of recovery. I know life has its ups
      and downs--it does for everyone. But I feel better able to cope and for now, for
      me, life is good; I hope this article is of help in making this possible for
      others.

PMID- 15468644
TI  - Pivotal therapeutic moments: a patient's perspective on surviving suicide.

PMID- 15468645
TI  - The implications for the clinician of adopting a recovery model: the role of
      choice in assertive treatment.
AB  - Theory is something rarely referred to in psychiatric rehabilitation. But the
      following, though opinion at this point, is meant to be seen as part of a pursuit
      of theory in psychiatric rehabilitation and in social science. The ideas behind
      the writing here draw heavily from the work of Patricia Deegan, yet truly are as
      old as the Declaration of Independence. They are strongly tied to the values of
      freedom, liberty, and the pursuit of happiness, as choice was expressed as a
      value in the Bill of Rights, and the Declaration of Independence. The social
      sciences and the physical sciences are seen as differing, in the same way as the
      social sciences at root draw from personal experiences while the physical
      sciences are more objectively determined. Thus, the author believes it not
      possible to put forward social theory without going beyond the purely objective,
      and including implicit, non-removable aspects of subjectivity. The author is
      herein proposing that the implications for the clinician of adopting a recovery
      model impact the issue of client choice. The Western tradition is now tied to the
      personal freedom of individual choice and opportunity. This paper explores the
      benefits of offering people with mental illnesses tangible choices in those areas
      of life, which impact upon the individual's consequences. The goal is to place
      the client in maximal control of his/her consequences, to the degree that the
      individual is capable of comprehending the nature of the choices involved; for
      the alternative of professionals choosing for their clients will inevitably
      result in learned helplessness. Although all of case management involves
      assertive treatment, this paper refers to cases in any modality of treatment in
      which professionals strongly advocate within the lives of and with the
      cooperation of clients, with special focus on the clients who encounter the
      greatest obstacles to successful treatment. The term "client" is employed here as
      the author is clearly referring to the dynamics of a professional relationship.
      The existence of helping professionals presupposes the existence of clients.

PMID- 15468646
TI  - Six Sigma adds new dimension to quality management processes.

PMID- 15468648
TI  - The benefits of sharing.

PMID- 15468647
TI  - A transformational approach to healthcare quality improvement.

PMID- 15468649
TI  - Diversion of controlled substances: a catalyst for change.
AB  - A quality improvement team was formed in response to a controlled substance
      diversion by an employee. The team's objectives were to track controlled
      substances throughout the institution and to design a system that would eliminate
      inappropriate access to controlled substances without negatively affecting
      patient care. The team utilized flow charts, staff interviews, and auditing tools
      to identify weaknesses within the current system. Subcommittees were formed to
      evaluate access and to develop an education campaign. It is the institution's
      responsibility to keep patients and staff safe by designing, implementing, and
      monitoring systems to appropriately control access to controlled substances.

PMID- 15468650
TI  - Diabetes preventive care and non-traumatic lower extremity amputation rates.
AB  - Clinical performance monitoring data on processes of care from a 3-year period
      were used to assess whether preventive foot care was associated with improved
      health outcomes in diabetes mellitus patients. Preventive foot care as well as
      sensory and pedal-pulse examinations were associated with reduced rates of Lower
      extremity amputation. It is believed that an administrative focus, resource
      direction, and improvement in process monitoring will lead to better patient
      outcomes. External review measures can be used by administrators and cLinicians
      to determine trends in quality of care and patient outcomes andto provide
      feedback on prevention efforts.

PMID- 15468651
TI  - Suzanne F. Delbanco on the Leapfrog Group and employer purchasing power.
      Interview by Pamela K. Scarrow.
AB  - Suzanne F. Delbanco, PhD MPH, is the first executive director of The Leapfrog
      Group, founded by the Business Roundtable. The Leapfrog Group's goal is to
      mobilize employer purchasing power to initiate breakthrough improvements in the
      safety, quality, and overall value of healthcare for American consumers. The
      group's growing consortium of more than 155 Fortune 500 companies and other large
      private and public healthcare purchasers provides health benefits to more than 34
      million Americans; these companies spend more than 62 billion dollars on
      healthcare annually. Dr. Delbanco is a member of the National Committee for
      Quality Assurance Purchaser Advisory Council and a board member of Bridges to
      Excellence. Before joining The Leapfrog Group, she was a senior manager at the
      Pacific Business Group on Health (PBGH), where she worked on the quality team.
      Prior to joining PBGH, she worked on reproductive health policy and the changing
      healthcare marketplace initiative at the Henry J. Kaiser Family Foundation. She
      has also consulted on health insurance coverage in the temporary employment
      industry and on the first statewide survey in California of MediCal
      beneficiaries, and worked as a community Liaison for Kaiser Permanente during the
      establishment of one of California's first County Organized Health Systems. She
      holds a PhD in public policy from the Goldman School of Public PoLicy and a MPH
      from the School of Public Health at the University of California, Berkeley.

PMID- 15468652
TI  - Breast cancer care: changing community standards.
AB  - A community hospital-based program was developed to improve breast cancer care in
      the community. A consensus was developed for what should be optimal care; a
      database was established to document the care being delivered in the community;
      and the data were analyzed to document changes in practice patterns over time.
      The major clinical benefits to patients included a significant improvement in
      needle biopsy rates, decreased utilization of second operative procedures,
      increased breast conservation surgery, conformity to guidelines for adjuvant
      chemotherapy administration, and a sizable increase in discovery of small breast
      cancers by screening mammography.

PMID- 15468653
TI  - Quality-of-care review of optometric records: inter-rater reliability.
AB  - As managed care organizations (MCOs) move into the realm of vision care, the
      issue of quality measurement has grown in relevance. This article assesses the
      inter-rater reliability of a medical record review instrument of a managed vision
      care plan. This study attempts to duplicate the continuous quality improvement
      initiative set forth by these MCOs. Twenty examiners, using the review instrument
      developed by the respective MCO, independently rated the records of 29 patients.
      Although the reviewers rated more than 86% of all records similarly, statistical
      analysis and further investigation deemed the instrument inconsistent and thus
      unreliable in its measurement.

PMID- 15468654
TI  - Using the quality improvement committee to establish accountability and yield
      results.
AB  - Healthcare organizations can respond effectively and efficiently to the needs of
      consumers and the demands of customers, accreditation agencies, and regulators by
      implementing a comprehensive quality improvement (QI) program. Using committees
      with cross-departmental representation, the QI program can facilitate review,
      analysis, prioritization of opportunities for improvement, and the facilitation
      of positive change. This article provides an example of how a managed behavioral
      healthcare organization responded to consumer needs and marketplace demands by
      using such an approach.

PMID- 15468655
TI  - Innovative ideas seminars: a method for eliciting innovations and their effect on
      quality and cost.

PMID- 15468656
TI  - Achieving a continual state of regulatory readiness.

PMID- 15468657
TI  - The relationship between real-time and time-integrated coarse (2.5-10 micrm),
      intermodal (1-2.5 microm), and fine (<2.5 microm) particulate matter in the Los
      Angeles basin.
AB  - A periodic review of the National Ambient Air Quality Standards for Particulate
      Matter by the U.S. Environmental Protection Agency (EPA) will assess the
      standards with respect to levels, particle size, and averaging times. Some
      members of the scientific community in the United States and Europe have
      suggested the use of PM1 instead of PM2.5 as the fine particle measurement
      standard. This proposed standard is intended to reduce the influence of coarse
      particle sources on PM2.5, because some evidence suggests that PM1-2.5 is
      dominated by coarse particulate matter (PM) sources. In this study, coarse (PM2.5
      10), intermodal (PM1-2.5), and fine (PM2.5) mass concentrations at four different
      sites are measured with continuous and time-integrated sampling devices. The main
      objective is to compare variations in these three size ranges while considering
      the effects of location, sources, weather, wind speed, and wind direction.
      Results show strong correlations between PM1 and intermodal PM in receptor sites.
      The contribution of PM1-2.5 to PM2.5 is highest in the summer months, most likely
      due to enhanced long-range transport. Coarse PM is poorly correlated with
      intermodal PM. Continuous data suggest that PM1 is growing into PM1-2.5 via
      complex processes involving stagnation of the aerosol during high relative
      humidity conditions, followed by advection during daytime hours.

PMID- 15468658
TI  - Semicontinuous PM2.5 sulfate and nitrate measurements at an urban and a rural
      location in New York: PMTACS-NY summer 2001 and 2002 campaigns.
AB  - Several collocated semicontinuous instruments measuring particulate matter with
      particle sizes < or =2.5 microm (PM2.5) sulfate (SO4(2-)) and nitrate (NO3-) were
      intercompared during two intensive field campaigns as part of the PM2.5
      Technology Assessment and Characterization Study. The summer 2001 urban campaign
      in Queens, NY, and the summer 2002 rural campaign in upstate New York (Whiteface
      Mountain) hosted an operation of an Aerosol Mass Spectrometer, Ambient
      Particulate Sulfate and Nitrate Monitors, a Continuous Ambient Sulfate Monitor,
      and a Particle-Into-Liquid Sampler with Ion Chromatographs (PILS-IC). These
      instruments provided near real-time particulate SO4(2-) and NO3- mass
      concentration data, allowing the study of particulate SO4(2-)/NO3- diurnal
      patterns and detection of short-term events. Typical particulate SO4(2-)
      concentrations were comparable at both sites (ranging from 0 to 20 microg/m3),
      while ambient urban particulate NO3- concentrations ranged from 0 to 11 microg/m3
      and rural NO3- concentration was typically less than 1 microg/m3. Results of the
      intercomparisons of the semicontinuous measurements are presented, as are results
      of the comparisons between the semicontinuous and time-integrated filter-based
      measurements. The comparisons at both sites, in most cases, indicated similar
      performance characteristics. In addition, charge balance calculations, based on
      major soluble ionic components of atmospheric aerosol from the PILS-IC and the
      filter measurements, indicated slightly acidic aerosol at both locations.

PMID- 15468659
TI  - Characterization of visibility impacts related to fine particulate matter in
      Canada.
AB  - Canada has recently established standards for the management of particulate
      matter (PM) air quality. National networks currently measure PM mass
      concentrations and chemical speciation. Methods used in the U.S. IMPROVE network
      are applied to the 1994--2000 Canadian fine PM data to obtain a regional
      reconstruction of the visibility based on particle composition. Nationally, the
      greatest light extinction occurs in the Windsor-Quebec City corridor. Variations
      in the dominant chemical species responsible for the reduction in visibility are
      presented for regions across the country. In most regions, sulfate and nitrate
      contribute most greatly to reduced visibility. The visibility implications of
      achieving the Canada-Wide Standard (CWS) across the country are evaluated, with
      the greatest improvement in visibility associated with achieving the CWS in
      southern Ontario. Elsewhere in the country, achieving the CWS will actually
      result in deteriorating air quality. Improving current estimates of visibility
      requires higher spatially and temporally resolved measurements of organic and
      elemental carbon fractions and particulate nitrate.

PMID- 15468660
TI  - A methodology to establish the morphology of ambient aerosols.
AB  - The morphology of ambient particulate matter (PM) is an important characteristic
      that seldom is measured and reported. A study was performed to determine the
      viability of a method to establish the distribution of shapes and the fractal
      dimensions of aggregates of ambient aerosols. Particles of PM with aerodynamic
      diameter less than or equal to 2.5 microm (PM2.5) were captured on different days
      via size-independent electrostatic precipitation at two sites in St. Louis and
      examined in a scanning electron microscope (SEM). Nonvolatile particles between
      0.1 and 2.5 microm were readily identified via SEM. Particle shapes were
      classified as fibrous, spherical, agglomerated, or "other." A computer program
      using the nested-squares algorithm was developed and used to determine the
      fractal dimensions of the aggregates. More particles were collected at the St.
      Louis-Midwest Supersite on June 14, 2002, than were collected on the Washington
      University campus loading dock on May 31, 2002, but the campus samples had a
      higher percentage of aggregates. On one day of sampling at the Supersite, the
      aggregate fraction was highest in the morning (14.3% between 7:00 and 9:00 a.m.)
      and steadily declined during the day (1.3% between 5:00 and 7:00 p.m.). The
      fractal dimensions of the aerosols were 1.65 in the morning (7:00-9:00 a.m.),
      decreased to 1.49 (11:00 a.m.-1:00 p.m.), and then increased to 1.87 (5:00-7:00
      p.m.). The results show that the fractal dimension is not a static value and that
      ambient aerosols are not perfectly spherical.

PMID- 15468661
TI  - Characterization of ultrafine particle number concentration and size distribution
      during a summer campaign in southwest Detroit.
AB  - This paper presents results from a study conducted in southwest Detroit from July
      20 to July 30, 2002, to characterize ambient ultrafine particles (dP < 0.1
      microm), and to examine the effect of local sources and meteorological parameters
      on the ultrafine number concentration and size distribution. The number
      concentrations of ambient particles in the size range of 0.01-0.43 microm were
      obtained from a scanning mobility particle sizer (SMPS). Meteorological
      parameters including ambient temperature, relative humidity, wind speed, wind
      direction, rainfall, and solar radiation flux were also monitored concurrently
      atop a 10-m tower. On average, ultrafine particles ranged from 1.4 x 10(4) to 2.5
      x 10(4) cm(-3), with significant diurnal and daily variations, and accounted for
      approximately 89% of the total number concentration (0.01 < dP < 0.43 microm).
      Time-series plots of the 5-min number concentrations revealed that peak
      concentrations often occurred during morning rush hour and/or around solar noon
      when photochemical activity was at a maximum. The morning traffic-related peak
      coincided with the NOx peak, whereas the photochemical-related peak correlated
      with solar radiation flux. On some days, the noon peak concentration was many
      times higher than the morning peak concentration. Although the number size
      distribution varied considerably over the course of the study, it typically
      exhibited one to three modes, with diameters around 0.01, 0.05, and 0.09 microm.
      Analysis of the influence of wind direction indicated that stationary sources
      could be one of the contributors to elevated ultrafine particle concentration.
      Overall, the data indicated that fossil fuel combustion and atmospheric gas-to
      particle conversion of precursor gases are the major sources of ultrafine
      particles in the southwest Detroit area during the summer.

PMID- 15468662
TI  - Characterization of carbon nanoparticles in ambient aerosols by scanning electron
      microscopy and model calculations.
AB  - Size-selected aerosol samples were analyzed by scanning electron microscopy (SEM)
      to explore (1) the relative concentration of individual and aggregated carbon
      nanoparticles (C-NPs) and (2) the combustion behavior of C-NP agglomerates. SEM
      analysis of low-coverage aerosol deposits showed that most of the C-NP matter is
      present in the form of chain-type agglomerates. The individual C-NPs in the
      agglomerates are remarkably similar in diameter (40+/-5 nm) and appear to be very
      tightly bound to the neighboring NPs. Comparison with literature data suggests
      that the agglomerates originated from diesel exhaust. After gently removing the
      water-soluble compounds from relatively thick layers of aerosol matter, the
      residues were exposed to increasing temperatures, for 1 hr at each step, followed
      by SEM analysis of the same sample area. C-NP agglomerates were found to
      disappear rapidly at temperatures exceeding approximately 470 degrees C. This
      observation constitutes the first direct visualization of the combustion of what
      appears to be the most important fraction of elemental carbon in ambient aerosol
      matter. The experimental studies were complemented by simple model calculations
      that aimed at assessing the size-dependent mass fraction of individual C-NPs in
      ambient aerosol matter. The results suggest that the mass fraction decreases from
      20+/-10% at particle diameters of approximately 30-40 nm to less than 0.1% above
      300 nm.

PMID- 15468663
TI  - Deposition and removal of fugitive dust in the arid southwestern United States:
      measurements and model results.
AB  - This work was motivated by the need to better reconcile emission factors for
      fugitive dust with the amount of geologic material found on ambient filter
      samples. The deposition of particulate matter with aerodynamic diameter less than
      or equal to 10 microm (PM10), generated by travel over an unpaved road, over the
      first 100 m of transport downwind of the road was examined at Ft. Bliss, near El
      Paso, TX. The field conditions, typical for warm days in the arid southwestern
      United States, represented sparsely vegetated terrain under neutral to unstable
      atmospheric conditions. Emission fluxes of PM10 dust were obtained from towers
      downwind of the unpaved road at 7, 50, and 100 m. The horizontal flux
      measurements at the 7 m and 100 m towers indicated that PM10 deposition to the
      vegetation and ground was too small to measure. The data indicated, with 95%
      confidence, that the loss of PM10 between the source of emission at the unpaved
      road, represented by the 7 m tower, and a point 100 m downwind was less than
      9.5%. A Gaussian model was used to simulate the plume. Values of the vertical
      standard deviation sigma(z) and the deposition velocity Vd were similar to the
      U.S. Environmental Protection Agency (EPA) ISC3 model. For the field conditions,
      the model predicted that removal of PM10 unpaved road dust by deposition over the
      distance between the point of emission and 100 m downwind would be less than 5%.
      However, the model results also indicated that particles larger than 10 microm
      (aerodynamic diameter) would deposit more appreciably. The model was consistent
      with changes observed in size distributions between 7 m and 100 m downwind, which
      were measured with optical particle counters. The Gaussian model predictions were
      also compared with another study conducted over rough terrain and stable
      atmospheric conditions. Under such conditions, measured PM10 removal rates over
      95 m of downwind transport were reported to be between 86% and 89%, whereas the
      Gaussian model predicted only a 30% removal. One explanation for the large
      discrepancy between measurements and model results was the possibility that under
      the conditions of the study, the dust plume was comparable in vertical extent to
      the roughness elements, thereby violating one of the model assumptions. Results
      of the field study reported here and the previous work over rough terrain bound
      the extent of particle deposition expected to occur under most unpaved road
      emission scenarios.

PMID- 15468664
TI  - Chemical speciation of PM2.5 collected during prescribed fires of the Coconino
      National Forest near Flagstaff, Arizona.
AB  - The use of prescribed fire is expected to increase in an effort to reduce the
      risk of catastrophic fire, particularly at urban/forest interfaces. Fire is a
      well-known source of particulate matter (PM) with particle sizes < or =2.5 microm
      (PM2.5), small diameter PM known to affect climate, visibility, and human health.
      In this work, PM2.5 was collected during seven first-entry burns (flaming and
      smoldering stages) and one maintenance burn of the Coconino National Forest.
      Samples were analyzed for organic and elemental carbon, cations (sodium,
      potassium [K+], and ammonium [NH4+]), anions (nitrate [NO3-] and sulfate), and 48
      elements (with atomic weights between sodium and lead). The PM2.5 contained high
      organic carbon levels (typically >90% by mass), commonly observed ions (K+, NH4+,
      and NO3-) and elements (K+, chlorine, sulfur, and silicon), as well as titanium
      and chromium. Flaming produced higher K+ and NH4+ levels than smoldering, and the
      elemental signature was more complex (20 versus 7 elements). Average organic
      carbon x 1.4 mass fractions (+/-standard deviation) were lower during flaming
      (92+/-14%) than during smoldering (124+/-24%). The maintenance (grassland) burn
      produced lower particle concentrations, lower NH4+ and NO3- levels, and higher K
      and chlorine levels than did the first-entry fires.

PMID- 15468665
TI  - Chemical composition of post-harvest biomass burning aerosols in Gwangju, Korea.
AB  - The main objective of this study was to investigate the chemical characteristics
      of post-harvest biomass burning aerosols from field burning of barley straw in
      late spring and rice straw in late fall in rural areas of Korea. A 12-hr
      integrated intensive sampling of particulate matter (PM) with an aerodynamic
      diameter less than or equal to 10 microm (PM10) and PM with an aerodynamic
      diameter less than or equal to 2.5 microm (PM2.5) biomass burning aerosols had
      been conducted continuously in Gwangju, Korea, during two biomass burning
      periods: June 4--15, 2001, and October 8--November 14, 2002. The fine and coarse
      particles of biomass burning aerosols were analyzed for mass and ionic,
      elemental, and carbonaceous species. The average fine and coarse mass
      concentrations of biomass burning aerosols were, respectively, 129.6 and 24.2
      microg/m3 in June 2001 and 47.1 and 33.2 microg/m3 in October--November 2002. An
      exceptionally high PM2.5 concentration of 157.8 microg/m3 was observed during
      biomass burning events under stagnant atmospheric conditions. In the fine mode,
      chlorine and potassium were unusually rich because of the high content of semi
      arid vegetation. Both organic carbon (OC) and elemental carbon increased during
      the biomass burning periods, with the former exhibiting a higher abundance. PM
      from the open field burning of agricultural waste has an adverse impact on local
      air quality and regional climate.

PMID- 15468666
TI  - Emission rates and comparative chemical composition from selected in-use diesel
      and gasoline-fueled vehicles.
AB  - Emission samples for toxicity testing and detailed chemical characterization were
      collected from a variety of gasoline- and diesel-fueled in-use vehicles operated
      on the Unified Driving Cycle on a chassis dynamometer. Gasoline vehicles included
      normal particle mass (particulate matter [PM]) emitters (tested at 72 and 30
      degrees F), "black" and "white" smokers, and a new-technology vehicle (tested at
      72 degrees F). Diesel vehicles included current-technology vehicles (tested at 72
      and 30 degrees F) and a high PM emitter. Total PM emission rates ranged from
      below 3 mg/mi up to more than 700 mg/mi for the white smoker gasoline vehicle.
      Emission rates of organic and elemental carbon (OC/EC), elements (metals and
      associated analytes), ions, and a variety of particulate and semi-volatile
      organic compounds (polycyclic aromatic hydrocarbons [PAH], nitro-PAH, oxy-PAH,
      hopanes, and steranes) are reported for these vehicles. Speciated organic
      analysis also was conducted on the fuels and lube oils obtained from these
      vehicles after the emissions testing. The compositions of emissions were highly
      dependent on the fuel type (gasoline vs. diesel), the state of vehicle
      maintenance (low, average, or high emitters; white or black smokers), and ambient
      conditions (i.e., temperature) of the vehicles. Fuel and oil analyses from these
      vehicles showed that oil served as a repository for combustion byproducts (e.g.,
      PAH), and oil-burning gasoline vehicles emitted PAH in higher concentrations than
      did other vehicles. These PAH emissions matched the PAH compositions observed in
      oil.

PMID- 15468667
TI  - Mixed-model statistical analysis of fuel, equipment, mileage, and driving
      schedule effects on particulate matter emissions from heavy diesel-powered
      vehicles.
AB  - An extensive experimental program has been conducted to evaluate the comparative
      effects of California Air Resources Board diesel fuel and an ultra-low-sulfur (S)
      diesel (with and without aftermarket passive filtering devices) on mass emissions
      of particulate matter (PM) in heavy vehicles. Tests have been performed on 20
      Class 8 trucks at two high-mileage levels using two different driving schedules.
      The design of the test program facilitates the use of mixed-model statistical
      analysis, which allows more appropriate treatment of the explanatory variables
      than normally achieved. The analysis suggests that the ultra-low-S diesel fuel
      yields extremely low mean PM emissions when used in conjunction with a
      particulate filter, even at high mileage, but that the estimates are highly
      variable. The high degree of uncertainty, caused at least in part by large
      vehicle-to-vehicle variation, may obscure the true PM response and adversely
      impact attainment of increasingly more stringent diesel PM emissions standards in
      the United States.

PMID- 15468668
TI  - Determination of the source areas contributing to regionally high warm season
      PM2.5 in eastern North America.
AB  - An ensemble-trajectory analysis technique known as Quantitative Transport Bias
      Analysis was applied to determine which geographic areas systematically
      contributed to above- and below-average fine particle mass (PM2.5) over eastern
      North America. Six-hour average measurements from 12 rural or suburban locations
      in eastern North America collected using a tapered element oscillating
      microbalance were individually associated with corresponding 3-day back
      trajectories for the warm seasons (May-September) of 2000 and 2001. Much of the
      populated areas of northeastern North America were implicated in the build-up of
      PM2.5 to above-average concentrations. The finer structure of the Quantitative
      Transport Bias Analysis pattern indicated that transport from the Ohio River
      Valley, particularly the eastern portion of this area, was most often associated
      with the highest PM2.5 concentrations. In addition, air masses originating over a
      relatively large area from southeast Ohio to the western part of Virginia and the
      western Kentucky to central Tennessee area tended to result in relatively high
      PM2.5 concentrations over northeastern North America. These observation-based
      findings were consistent with the spatial distribution of the main sulfur dioxide
      emissions sources and the major oxides of nitrogen point sources.

PMID- 15468669
TI  - Assessing source characteristics of PM2.5 in the eastern United States using
      positive matrix factorization.
AB  - Fine aerosol (PM2.5) measurements obtained from the first year of operation of
      the nationwide network of PM2.5 monitors were studied with the factor analysis
      technique of positive matrix factorization (PMF). PM2.5 mass concentration data
      were extracted from the Atmospheric Information Retrieval System (AIRS) database
      of the U.S. Environmental Protection Agency (EPA). PMF was applied to
      measurements at more than 350 monitoring locations in the eastern half of the
      United States. Data consisted of PM2.5 24-hr averaged concentrations measured
      every third day from April through December 1999. The PMF model suggested six
      factors representing source influences to the PM2.5 mass concentrations at
      measurement sites. Factor 5, covering much of the Appalachian states, exhibited
      significant seasonal behavior.

PMID- 15468670
TI  - Source apportionment of indoor, outdoor, and personal PM2.5 in Seattle,
      Washington, using positive matrix factorization.
AB  - As part of a large exposure assessment and health-effects panel study, 33 trace
      elements and light-absorbing carbon were measured on 24-hr fixed-site filter
      samples for particulate matter with an aerodynamic diameter <2.5 microm (PM2.5)
      collected between September 26, 2000, and May 25, 2001, at a central outdoor
      site, immediately outside each subject's residence, inside each residence, and on
      each subject (personal sample). Both two-way (PMF2) and three-way (PMF3) positive
      matrix factorization were used to deduce the sources contributing to PM2.5. Five
      sources contributing to the indoor and outdoor samples were identified:
      vegetative burning, mobile emissions, secondary sulfate, a source rich in
      chlorine, and a source of crustal-derived material. Vegetative burning
      contributed more PM2.5 mass on average than any other source in all
      microenvironments, with average values estimated by PMF2 and PMF3, respectively,
      of 7.6 and 8.7 microg/m3 for the outdoor samples, 4 and 5.3 microg/m3 for the
      indoor samples, and 3.8 and 3.4 microg/m3 for the personal samples. Personal
      exposure to the combustion-related particles was correlated with outdoor sources,
      whereas exposure to the crustal and chlorine-rich particles was not. Personal
      exposures to crustal sources were strongly associated with personal activities,
      especially time spent at school among the child subjects.

PMID- 15468671
TI  - Outdoor versus indoor contributions to indoor particulate matter (PM) determined
      by mass balance methods.
AB  - This study compares an indoor-outdoor air-exchange mass balance model (IO model)
      with a chemical mass balance (CMB) model. The models were used to determine the
      contribution of outdoor sources and indoor resuspension activities to indoor
      particulate matter (PM) concentrations. Simultaneous indoor and outdoor
      measurements of PM concentration, chemical composition, and air-exchange rate
      were made for five consecutive days at a single-family residence using particle
      counters, nephelometers, and filter samples of integrated PM with an aerodynamic
      diameter of less than or equal to 2.5 microm (PM2.5) and PM with an aerodynamic
      diameter of less than or equal to 5 microm (PM5). Chemical compositions were
      determined by inductively coupled plasma mass-spectrometry. During three high
      activity days, prescribed activities, such as cleaning and walking, were
      conducted over a period of 4-6 hr. For the remaining two days, indoor activities
      were minimal. Indoor sources accounted for 60-89% of the PM2.5 and more than 90%
      of the PM5 for the high-activity days. For the minimal-activity days, indoor
      sources accounted for 27-47% of PM2.5 and 44-60% of the PM5. Good agreement was
      found between the two mass balance methods. Indoor PM2.5 originating outdoors
      averaged 53% of outdoor concentrations.

PMID- 15468672
TI  - Estimated hourly personal exposures to ambient and nonambient particulate matter
      among sensitive populations in Seattle, Washington.
AB  - Epidemiological studies of particulate matter (PM) routinely use concentrations
      measured with stationary outdoor monitors as surrogates for personal exposure.
      Despite the frequently reported poor correlations between ambient concentrations
      and total personal exposure, the epidemiologic associations between ambient
      concentrations and health effects depend on the correlation between ambient
      concentrations and personal exposure to ambient-generated PM. This paper
      separates personal PM exposure into ambient and nonambient components and
      estimates the outdoor contribution to personal PM exposures with continuous light
      scattering data collected from 38 subjects in Seattle, WA. Across all subjects,
      the average exposure encountered indoors at home was lower than in all other
      microenvironments. Cooking and being at school were associated with elevated
      levels of exposure. Previously published estimates of particle infiltration
      (Finf) were combined with time-location data to estimate an ambient contribution
      fraction (alpha, mean = 0.66+/-0.21) for each subject. The mean alpha was
      significantly lower for subjects monitored during the heating season (0.55+/
      0.16) than for those monitored during the nonheating season (0.80+/-0.17). Our
      modeled alpha estimates agreed well with those estimated with the sulfur-tracer
      method (slope = 1.08; R2 = 0.67). We modeled exposure to ambient and nonambient
      PM with both continuous light scattering and 24-hr gravimetric data and found
      good agreement between the two methods. On average, ambient particles accounted
      for 48% of total personal exposure (range = 21-80%). The personal activity
      exposure was highly influenced by time spent away from monitored
      microenvironments. The median hourly longitudinal correlation between central
      site concentrations and personal exposures was 0.30. Although both alpha and the
      nonambient sources influence the personal-central relationship, the latter seems
      to dominate. Thus, total personal exposure may be poorly predicted by stationary
      outdoor monitors, particularly among persons whose PM exposure is dominated by
      nonambient exposures, for example, those living in tightly sealed homes, those
      who cook, and children.

PMID- 15468673
TI  - Associations and lags between air pollution and acute respiratory visits in an
      ambulatory care setting: 25-month results from the aerosol research and
      inhalation epidemiological study.
AB  - Particulate matter (PM) has been associated with adverse respiratory outcomes in
      numerous studies that utilized data from emergency room visits, hospital
      admissions, and mortality records. This study is unique in its investigation of
      associations of air pollution measures, including components of PM, with health
      outcomes in an ambulatory-care setting. Visit data were collected from Kaiser
      Permanente, a not-for-profit health maintenance organization in the metropolitan
      Atlanta, GA, area. Kaiser Permanente collaborated on the Aerosol Research
      Inhalation Epidemiological Study (ARIES), which provided detailed information on
      the characteristics of air pollutants. The Kaiser Permanente study was a time
      series investigation of the possible associations between daily levels of
      suspended PM, inorganic gases, and polar volatile organic compounds and
      ambulatory care acute visit rates during the 25-month period from August 1, 1998,
      to August 31, 2000. For this interim analysis, the a priori 0-2 days lagged
      moving average, as well as the 3-5 days and 6-8 days lagged moving averages, of
      air quality measures were investigated. Single-pollutant Poisson general linear
      modeling was used to model daily visit counts for asthma and upper and lower
      respiratory infections (URI and LRI) by selected air quality metrics, controlling
      for temporal trends and meteorological variables. Most of the statistically
      significant positive associations were for the 3-5 days lagged air quality
      metrics with child asthma and LRI.

PMID- 15468674
TI  - Embryonic stem cells form articular cartilage, not teratomas, in osteochondral
      defects of rat joints.
AB  - Embryonic stem (ES) cells are considered to be a potential tool for repairing
      articular cartilage defects, but so far it has been impossible to cause these
      cells to differentiate into chondrocytes exclusively, either in vivo or in vitro.
      To explore a potential new cell source of cell transplantation for articular
      cartilage defects, we transplanted ES cells into articular cartilage defects in
      immunosuppressed rats. ES cells (AB2.2 or CCE cells) were transplanted into
      articular cartilage defects in the patellar groove of immunosuppressed rats
      treated with cyclosporine. The cells were histologically observed until 8 weeks
      after transplantation. To determine whether the repair tissue in the defect in
      the AB2.2-transplanted group was derived from the transplanted cells, the
      neomycin-resistant gene, which had been transfected into AB2.2 cells but does not
      exist in rat cells, was used for detection. The cells produced cartilage,
      resulting in repair of the defects from 4 weeks until 8 weeks after the
      transplantation without forming any teratomas. The neomycin-resistant gene was
      detected in every sample, demonstrating that the repair tissue in the AB2.2
      transplanted group was derived from the transplanted AB2.2 cells. The environment
      of osteochondral defects is chondrogenic for ES cells. ES cells may thus be a
      potential tool for repairing articular cartilage defects.

PMID- 15468675
TI  - Effects of osteogenic induction on mesenchymal cells from fetal and maternal
      parts of human placenta.
AB  - To clarify whether the mesenchymal cells derived from human placenta were
      available for bone regeneration, we investigated the effects of osteogenic
      induction on mesenchymal cells of fetal and maternal parts of the placenta. The
      osteogenic-induced mineralization in both types of cells was measured by von
      Kossa staining, and the calcium concentration and the expression of osteogenic
      markers were assayed by RT-PCR. In the mesenchymal cells of both parts,
      osteopontin, osteocalcin, alkaline phosphatase, and collagen type I, which are
      osteogenic markers, were expressed. Moreover, the mesenchymal cells of the fetal
      part of the placenta were mineralized for 3 weeks, but those of the maternal part
      were not. These results showed that the mesenchymal cells derived from human
      placenta had an osteogenic phenotype and that only the mesenchymal cells of the
      fetal part were capable of being used as a cell source for bone reconstitution.

PMID- 15468676
TI  - Translational research for injectable tissue-engineered bone regeneration using
      mesenchymal stem cells and platelet-rich plasma: from basic research to clinical
      case study.
AB  - Translational research involves application of basic scientific discoveries into
      clinically germane findings and, simultaneously, the generation of scientific
      questions based on clinical observations. At first, as basic research we
      investigated tissue-engineered bone regeneration using mesenchymal stem cells
      (MSCs) and platelet-rich plasma (PRP) in a dog mandible model. We also confirmed
      the correlation between osseointegration in dental implants and the injectable
      bone. Bone defects made with a trephine bar were implanted with graft materials
      as follows: PRP, dog MSCs (dMSCs) and PRP, autogenous particulate cancellous bone
      and marrow (PCBM), and control (defect only). Two months later, dental implants
      were installed. According to the histological and histomorphometric observations
      at 2 months after implants, the amount of bone-implant contact at the bone
      implant interface was significantly different between the PRP, PCBM, dMSCs/ PRP,
      native bone, and control groups. Significant differences were also found between
      the dMSCs/PRP, native bone, and control groups in bone density. These findings
      indicate that the use of a mixture of dMSCs/ PRP will provide good results in
      implant treatment compared with that achieved by autogenous PCBM. We then applied
      this injectable tissue-engineered bone to onlay plasty in the posterior maxilla
      or mandible in three human patients. Injectable tissue-engineered bone was
      grafted and, simultaneously, 2-3 threaded titanium implants were inserted into
      the defect area. The results of this investigation indicated that injectable
      tissue-engineered bone used for the plasty area with simultaneous implant
      placement provided stable and predictable results in terms of implant success. We
      regenerated bone with minimal invasiveness and good plasticity, which could
      provide a clinical alternative to autogenous bone grafts. This might be a good
      case of translational research from basic research to clinical application.

PMID- 15468677
TI  - Osteogenic potential of cultured bone/ceramic construct: comparison with marrow
      mesenchymal cell/ceramic composite.
AB  - Osteogenesis occurs in porous hydroxyapatite (HA) when porous HA blocks combined
      with marrow mesenchymal cells are grafted in vivo. In vitro bone formation occurs
      in HA pores when HA combined with marrow cells is cultured in osteogenic medium
      containing dexamethasone. This cultured bone/HA construct possesses higher
      osteogenic ability when it is grafted in vivo. In the present study, we compared
      the osteogenic potential of a cultured bone/HA construct with that of a marrow
      mesenchymal cell/HA composite. Marrow cells were obtained from the femoral bone
      shaft of 7-week-old, male Fischer 344 rats and were cultured in T-75 flasks.
      Cells were concentrated, then frozen and stored in liquid nitrogen for 6 months.
      The cryopreserved cells were then thawed and prepared for subculture in porous HA
      (5 x 5 x 5 mm, Interpore 500) and for implantation with porous HA. After 2 weeks
      of subculture, three cultured bone/HA constructs were separately implanted in the
      right side of the back of each syngeneic 7-week-old male Fischer rat, and three
      thawed cell/HA composites (without subculture) were separately implanted in the
      left side. These implants were harvested at 2 or 4 weeks postimplantation, and
      prepared for histological, biochemical, and genetic analysis. Alkaline
      phosphatase activity and osteocalcin content of cultured bone/HA constructs were
      much higher than those of the cell/HA composites at 2 and 4 weeks
      postimplantation. Histological examination and gene expression data agreed with
      these findings. The culture technique discussed herein should facilitate the
      development of biosynthetic bone implants with higher osteogenic capacity.

PMID- 15468678
TI  - Bone tissue engineering using novel interconnected porous hydroxyapatite ceramics
      combined with marrow mesenchymal cells: quantitative and three-dimensional image
      analysis.
AB  - We developed fully opened interconnected porous calcium hydroxyapatite ceramics
      having two different pore sizes. One has pores with an average size of 150 microm
      in diameter, an average 40-microm interconnecting pore diameter, and 75% porosity
      (HA150). The other has pores with an average size of 300 microm in diameter, an
      average 60-100-microm interconnecting pore diameter, and 75% porosity (HA300).
      Because of its smaller pore diameter, HA150 has greater mechanical strength than
      that of HA300. These ceramics were combined with rat marrow mesenchymal cells and
      cultured for 2 weeks in the presence of dexamethasone. The cultured ceramics were
      then implanted into subcutaneous sites in syngeneic rats and harvested 2-8 weeks
      after implantation. All the implants showed bone formation inside the pore areas
      as evidenced by decalcified histological sections and microcomputed tomography
      images, which enabled three-dimensional analysis of the newly formed bone and
      calculation of the bone volume in the implants. The bone volume increased over
      time. At 8 weeks after implantation, extensive bone volume was detected not only
      in the surface pore areas but also in the center pore areas of the implants. A
      high degree of alkaline phosphatase activity with a peak at 2 weeks and a high
      level of osteocalcin with a gradual increase over time were detected in the
      implants. The levels of these biochemical parameters were higher in HA150 than in
      HA300. The results indicate that a combination of HA150 and mesenchymal cells
      could be used as an excellent bone graft substitute because of its mechanical
      properties and capability of inducing bone formation.

PMID- 15468679
TI  - Enhancement of in vitro osteoblastic potential after selective sorting of
      osteoblasts with high alkaline phosphatase activity from human osteoblast-like
      cells.
AB  - In this article we describe the expansion of in vitro osteogenic capability of
      human osteoblasts (HOS cells) after sorting by fluorescence-activated cell
      sorting (FACS) with the osteoblastic marker of human bone alkaline phosphatase
      (AP) monoclonal antibody. After culturing for 7 days, the HOS cells were
      incubated with fluorescein isothiocyanate (FITC)-labeled AP monoclonal antibody.
      The antibody recognized the cells with high AP activity (high AP cells), which
      were about 76% of the total cells. After the HOS cells were sorted, the high AP
      cells could be recovered, and almost all of them reacted strongly with the AP
      antibody. Therefore, we were able to condense the high AP cells about 1.3 times.
      We further cultured the sorted cells as well as the unsorted control cells. After
      the initial seeding, the culturing periods for both groups of cells were 20 days.
      At the end of this period, we measured AP activity per DNA and osteocalcin
      contents. In contrast to the low condensation ratio of the high AP cells in the
      sorted fraction, the AP activity and osteocalcin contents were about nine times
      and four times greater than those of the unsorted cells, respectively. These
      results demonstrated that using the sorting technique to isolate the high AP
      cells might be a useful method for applications in bone tissue engineering.

PMID- 15468680
TI  - Propagation of adult rat bone marrow-derived hepatocyte-like cells by serial
      passages in vitro.
AB  - Previously, we found that hepatocyte growth factor receptor (c-Met)-and alpha
      fetoprotein (AFP)-expressing cells were present in adult rat bone marrow, and
      that these cells also expressed hematopoietic stem cell markers, such as CD34,
      Thy-1, and c-Kit. When bone marrow cells were cultured in a hepatocyte growth
      medium (HGM) with HGF and EGF, colonies composed of polygonal cells resembling
      mature hepatocytes appeared by 2 weeks and grew very slowly because of overgrowth
      of stromal cells. At days 34-41, 2-mm2 sheets of hepatocyte-like cells were cut
      out of their colonies by scratching with an injection needle under observation
      with a phase contrast microscope, transferred into wells of 24-well plates, and
      cultured in the HGM medium in the presence or absence of HGF and EGF. When cells
      reached confluence, cells were detached with trypsin and EDTA and transferred
      step by step into bigger culture vessels. Thus, hepatocyte-like cells were
      expanded 1000-fold during less than 4 months. These cells were
      immunocytochemically stained for albumin and also for AFP and the hematopoietic
      stem cell markers described above, showing characteristics of oval cells. By RT
      PCR, we detected mRNAs of tryptophan-2,3-dioxygenase and tyrosine
      aminotransferase, markers of hepatocytes at a terminal differentiation stage. The
      present culture system may be useful for supply of hepatocyte resources for cell
      transplantation therapy.

PMID- 15468681
TI  - Functional activity of human hepatoma cells transfected with adenovirus-mediated
      hepatocyte nuclear factor (HNF)-4 gene.
AB  - Fulminant hepatic failure (FHF) is still associated with high mortality despite
      recent advances in medical management. There is need of an effective and safe
      bioartificial liver (BAL) support to help keep patients with FHF alive until an
      organ becomes available for transplantation or the native liver recovers. The aim
      of this study was to establish highly functional liver cells by means of
      transfecting hepatocyte nuclear factor (HNF)-4 gene for the development of BAL.
      We constructed adenovirus vector carrying rat HNF-4 cDNA, and transfected to
      hepatoma-derived cell lines, HepG2 and HuH-7, to enforce expression of the
      exogenous HNF-4 gene. We analyzed expression of HNF-4, HNF-1, and liver-specific
      genes in cells infected by the adenovirus vector expressing HNF-4. Adenovirus
      mediated HNF-4 gene transfer resulted in increases in expressions of HNF-4, HNF
      1, and liver-specific genes such as apolipoproteins, alpha1-antitrypsin (alpha1
      AT), phosphoenolpyruvate carboxy-kinase, cytochrome P450 families, and glutamine
      synthetase in transfected hepatoma cells. Cells overexpressing HNF-4 removed
      ammonia from medium supplemented with NH4Cl to a greater extent than control
      cells. These findings demonstrated that transfected cell lines restored
      differentiated gene expressions and liver-specific function by the overproduction
      of HNF-4. HNF-4-overexpressing hepatocyte cell lines are useful for bioreactor of
      BAL systems.

PMID- 15468682
TI  - Transplanted mesenchymal stem cells are effective for skin regeneration in acute
      cutaneous wounds.
AB  - Mesenchymal stem cells (MSCs) possess the capacity for site-specific
      differentiation of cell types in response to cues provided by different organs.
      This phenomenon suggests that MSCs participate in cutaneous wound regeneration.
      However, there are no prior reports on the influence of the local application of
      MSCs on cutaneous wound regeneration. To examine the effects of MSCs on wound
      regeneration, we cultured bone marrow cells of the femur of rats and treated the
      plastic adherent cells with a differentiation medium to induce differentiation.
      After treatment, we found that the bone marrow-derived plastic adherent cells
      possessed myogenesis, chondrogenesis, and adipogenesis capabilities, indicating
      that these cells are MSCs. The bone marrow-derived plastic adherent cells were
      injected intradermally into the skin of rats, and linear full-thickness
      incisional wounds were made immediately through the injected area. At 14 days
      after operation, wounds transplanted with bone marrow-derived plastic adherent
      cells had healed with very fine scars. Collagen architecture was thick and
      appeared to be similar to normal dermis. Histomorphologic scale analysis
      demonstrated significant differences between the control and the wounds
      transplanted with bone marrow-derived plastic adherent cells. These results
      indicate that transplanted MSCs can respond quite normally to wound healing and
      regenerate dermal structure.

PMID- 15468683
TI  - Transplantation of nonvascularized kidney tissue fragments into the rat liver
      with the aim of preserving renal function.
AB  - For research in regenerative medicine, not only the study of cellular
      pluripotency but also knowledge of the reorganization of tissue structure is
      crucial. However, the latter will probably be more difficult to acquire. When
      small fragments of kidney (approx. 1 x 1 mm) were implanted in the liver of
      syngeneic LEW rats, the tissue survived at least 2 weeks with retention of normal
      structure including glomeruli and tubules. In contrast, no kidney structure
      survived when transplanted to subcutaneous sites, omentum, or spleen. Molecules
      involved in renal tubular function, such as megalin and glut2 transporter
      protein, were detectable in the implanted tissue by immunohistochemistry,
      suggesting that the cells were biologically active. Survival of cortex, medulla,
      and calyx tissues was then compared. All three components were still detectable 8
      weeks after transplantation but cortex and medulla were replaced by granuloma at
      6 months. Only calyx tissue survived for up to 12 months after transplantation.
      There was no marked difference in tissue survival, either when the recipient
      liver was partially resected or when infantile donor kidney was implanted instead
      of adult kidney. The present method opens new avenues in the development of
      regenerative medicine (i.e., tissue transplantation) as an intermediate modus
      between organ transplantation and cell transplantation.

PMID- 15468684
TI  - Vigorous neuronal differentiation of amplified and grafted basic fibroblast
      growth factor-responsive neurospheres derived from neuroepithelial stem cells.
AB  - Neuroepithelial stem cells (NESCs) have emerged as a possible donor material
      aimed at neural transplantation for the repair of damaged neural circuitry,
      particularly because of their propensity to differentiate into neurons. We
      previously ascertained in vitro that NESCs derived from rat early embryos could
      be amplified in culture containing basic fibroblast growth factors (bFGF), and
      that neurospheres grown for 7 days in the culture had a strong tendency to
      differentiate into neurons. In this report, we analyze immunohistochemically the
      biological nature of bFGF-responsive neurospheres derived from NESCs. We first
      succeeded in amplifying the number of NESCs from the mesencephalic neural plate
      of embryonic day 10 Wistar rats with the addition of bFGF. Grown neurospheres
      were labeled with bromodeoxyuridine (BrdU) in vitro and were stereotactically
      transplanted into the right striatum of the normal adult Wistar rat. Two weeks
      after transplantation, a viable graft in the host brain was observed. While many
      BrdU/Hu double positive cells were seen in the graft, and a few BrdU/nestin
      double positive cells were also seen, no BrdU/GFAP double positive cells could be
      identified. These results suggested that bFGF-responsive neurospheres derived
      from NESCs demonstrated a propensity to differentiate into neurons in the adult
      brain environment. Furthermore, following in vitro amplification of the original
      stem cell number with bFGF, the grown neurospheres preserved their propensity to
      differentiate vigorously into neurons. NESCs are thus suggested as a feasible
      candidate for intracerebral grafting donor materials aimed at reconstruction of
      damaged neural circuits.

PMID- 15468685
TI  - Therapeutic angiogenesis by autologous bone marrow cell implantation for
      refractory chronic peripheral arterial disease using assessment of
      neovascularization by 99mTc-tetrofosmin (TF) perfusion scintigraphy.
AB  - We investigated efficacy and safety of implantation of autologous bone marrow
      mononuclear cells plus platelets, including endothelial progenitor cells (EPCs),
      for recovering refractory chronic peripheral arterial disease (PAD) using visual
      and quantitative analyses by 99mTc-tetrofosmin (TF) perfusion scintigraphy, and
      also investigated various quantitative assessments objectively. We performed 12
      consecutive cases and 19 limbs and hands with severe chronic PAD that were almost
      Fontaine class IV (11/12 cases, about 92%) in this trial. This treatment was very
      effective in relieving severe pain of PAD, especially for Buerger's disease. We
      used a visual analog scale (VAS) for measurement of pain level. The maximum pain
      level before implantation was 66.5+/-5.0 mm, and it decreased to 12.1+/-2.2 mm
      after implantation (p < 0.001). Rest pain in legs and fingers was resolved in 11
      cases (11/12 cases, 92%). All patients could measure pain-free walking time on a
      treadmill, which improved remarkably (140+/-53 s before implantation vs. 451+/-74
      s after implantation, p = 0.034). Resting ankle brachial pressure index (ABI) in
      legs implanted with bone marrow mononuclear cells was also improved (0.65+/-0.08
      before implantation vs. 0.73+/-0.07 after implantation, p = 0.055). According to
      99mTc-TF perfusion scintigraphy, the proximal area (region from knee to ankle)
      was 1.32+/-0.10 before implantation versus 1.56+/-0.11 after implantation (p =
      0.007). 99Tc-TF perfusion scintigraphy in the distal area (region from ankle to
      end of toes, or from wrist to end of fingers) was 0.79+/-0.06 before implantation
      versus 0.83+/-0.06 after implantation (p = 0.29). Ischemic legs and hands that
      were injected showed increased perfusion blood flow. 99mTc-TF perfusion
      scintigraphy was effective to estimate visual and quantitative analysis of
      collateral vessels in neovascularization. We were successful with this new
      treatment for the most severe, chronic PAD that was not curable by any of the
      current treatments. Thus, this therapeutic angiogenesis could be a new strategy
      for saving severe ischemic limbs and hands.

PMID- 15468686
TI  - In vivo tissue-engineered small-caliber arterial graft prosthesis consisting of
      autologous tissue (biotube).
AB  - In this study, vascular-like tubular tissues called biotubes, consisting of
      autologous tissues, were prepared using in vivo tissue engineering. Their
      mechanical properties were evaluated for application as a small-caliber
      artificial vascular prosthesis. The biotubes were prepared by embedding six kinds
      of polymeric rods [poly(ethylene) (PE), poly(fluoroacetate) (PFA), poly(methyl
      methacrylate) (PMMA), segmented poly(urethane) (PU), poly(vinyl chloride) (PVC),
      and silicone (Si)] as a mold in six subcutaneous pouches in the dorsal skin of
      New Zealand White rabbits. For rods apart from PFA, biotubes were constructed
      after 1 month of implantation by encapsulation around the polymeric implants. The
      wall thickness of the biotubes ranged from about 50 to 200 microm depending on
      the implant material and were in the order PFA < PVC < PMMA < PU < PE. As for PE,
      PMMA, and PVC, the thickness increased after 3 months of implantation and ranged
      from 1.5-to 2-fold. None of the biotubes were ruptured when a hydrostatic
      pressure was gradually applied to their lumen up to 200 mmHg. The relationship
      between the intraluminal pressure and the external diameter, which was highly
      reproducible, showed a "J"-shaped curve similar to the native artery. The tissue
      mostly consisted of collagen-rich extracellular matrices and fibroblasts.
      Generally, the tissue was relatively firm and inelastic for Si and soft for PMMA.
      For PMMA, PE, and PVC the stiffness parameter (beta value; one of the indexes for
      compliance) of the biotubes obtained was similar to those of the human coronary,
      femoral, and carotid arteries, respectively. Biotubes, which possess the ability
      for wide adjustments in their matrices, mechanics, shape, and luminal surface
      design, can be applied for use as small-caliber blood vessels and are an ideal
      implant because they avoid immunological rejection.

PMID- 15468687
TI  - Development of a hydroxyapatite/collagen nanocomposite as a medical device.
AB  - The effect of cross-linking of a hydroxyapatite/collagen (HA/Col) nanocomposite,
      in which HA nanocrystals and collagen fibers are aligned like natural bone by a
      self-organization mechanism between HA and collagen in vitro, on mechanical
      properties was examined. The influence of degree of cross-linking, as well as
      rhBMP-2 preadsorption to the composite on the substitution pattern and rate with
      bone, was examined. In Experiment 1, anterior fusion was carried out at the C3-C4
      vertebrae on 10 dogs and they were implanted as follows: without cross-linking
      and without adsorbed rhBMP-2 (three dogs), with cross-linking and without
      adsorbed rhBMP-2 (three dogs), without cross-linking and with adsorbed rhBMP-2
      (two dogs), and with cross-linking and adsorbed rhBMP-2 (two dogs). Implants were
      removed from each dog for histology determinations after 12, 16, and 24 weeks in
      the non-rhBMP-treated groups, and after 16 and 24 weeks in the rhBMP-treated
      groups. In Experiment 2, the HA/Col composites with cross-linking and both with
      and without rhBMP-2 pretreatment were implanted into a bone defect of 20 mm made
      in the central part of tibiae in dogs (N = 3 in each group). As a control, bone
      defects of 20 mm remained without implantation (N = 3). The dogs were allowed to
      walk using an Ilizarov extra skeletal fixator. The implants were removed after
      12, 16, and 24 weeks from one dog in each group. The cross-linking of the HA/Col
      composite was effective in controlling both the mechanical strength and
      bioresorbability. A "self-organization process" on the HA/Col implant surface
      resulted in the formation of bone remodeling units in and around the implant.
      Radiographic and histological findings suggest that a combined treatment of cross
      linking of the HA/Col composite with preadsorption of rhBMP-2 molecules may be a
      very suitable replacement of existing ceramic systems in the anterior fusion of
      the cervical spine, as well as inlay grafting of bone defects in weight-bearing
      sites.

PMID- 15468688
TI  - Collagen vitrigel: a novel scaffold that can facilitate a three-dimensional
      culture for reconstructing organoids.
AB  - Three-dimensional reconstructed organoids in vitro are valuable for not only
      regenerative medicine but also drug development. However, the manipulation of
      conventional three-dimensional cultures is not simple. We describe a nylon
      membrane ring-embedded or a pressed silk sheet-embedded scaffold made of collagen
      "vitrigel" that can facilitate three-dimensional cultures for reconstructing an
      epithelial-mesenchymal model or a hard connective tissue model, respectively.
      Here we define vitrigel as a gel in a stable state produced by rehydration after
      the vitrification of a traditional hydrogel. The collagen vitrigel was
      successfully prepared in three steps involving a gelation process in which a cold
      and clear neutral salt solution containing type I collagen formed an opaque and
      soft gel by incubation at 37 degrees C, a vitrification process in which the gel
      becomes a rigid material like glass after sufficient drying out, and finally a
      rehydration process to convert the vitrified material into a thin and transparent
      gel membrane with enhanced gel strength. The framework-embedded collagen vitrigel
      scaffold that can be easily reversed by forceps was prepared by inserting a nylon
      ring or a silk sheet in the collagen solution prior to the gelation. The scaffold
      enabled culturing anchorage-dependent cells on both surfaces of the collagen
      vitrigel by the manipulation of two-dimensional cultures and consequently
      resulted in reconstructing a three-dimensional organoid. An intestinal epithelial
      mesenchymal model was reconstructed by coculturing fibroblasts on the opposite
      side of monolayered Caco-2 cells on the nylon ring-embedded collagen vitrigel.
      Also, fibroblasts seeded on both surfaces of the silk sheet-embedded collagen
      vitrigel proliferated well and formed multilayers and some cells invaded into the
      vitrigel framed by the network of numerous strong silk filaments, suggesting a
      reconstruction of a hard connective tissue model. These data demonstrate that the
      collagen vitrigel is a valuable scaffold for tissue engineering.

PMID- 15468689
TI  - [What is your diagnosis? Cardiac amyloidosis].

PMID- 15468690
TI  - [Hypokalemia. Main symptoms: muscle weakness, heart rhythm disorders].

PMID- 15468691
TI  - [Importance of timing of music therapy in chemotherapy of cancer patients].
AB  - Neither the measured stress-hormones, nor Beta-Endorphin have been influenced by
      music therapy. Music therapy should be initiated before the beginning of
      chemotherapy, preferably shortly after the operation. The greatest profit of an
      accompanying music therapy is between the chemotherapy courses, because the whole
      energy of the patient during chemotherapy is directed to questions, worries and
      practical aspects.

PMID- 15468692
TI  - [Transabdominal sonography of the gastrointestinal tract: what is the clinical
      value?].

PMID- 15468693
TI  - [Bilateral shoulder-hand syndrome revealing hypothyroidism and colon carcinoma].
AB  - The autors describe a case of a bilateral shoulder-hand syndrome. A Hashimoto's
      thyroiditis bound hypothyroidism was retained as promoting factor. Rheumatic
      manifestations amended slowly with a treatment of corticosteroids associated to
      thyroid hormones replacement. Eighteen months after the onset of the rheumatic
      complaints, a colorectal cancer was also diagnosed. The respective role of
      hypothyroidism and cancer in the emergence of this severe shoulder-hand syndrome
      is discussed.

PMID- 15468695
TI  - [Status febrilis and multiple diffuse calcifications in the spleen].

PMID- 15468694
TI  - [Clopidogrel as basic therapy in high-risk stroke patients].

PMID- 15468697
TI  - [Bitter healing power].

PMID- 15468696
TI  - [Rhabdomyolysis, compartment syndrome, acute kidney and heart failure in a youth:
      the same etiology?].

PMID- 15468698
TI  - Viewing zones in three-dimensional imaging systems based on lenticular, parallax
      barrier, and microlens-array plates.
AB  - The viewing zone of autostereoscopic imaging systems that use lenticular,
      parallax-barrier, and microlens-array plates as the viewing-zone-forming optics
      is analyzed in order to verify the image-quality differences between different
      locations of the zone. The viewing zone consists of many subzones. The images
      seen at most of these subzones are composed of at least one image strip selected
      from the total number of different view images displayed. These different view
      images are not mixed but patched to form a complete image. This image patching
      deteriorates the quality of the image seen at different subzones. We attempt to
      quantify the quality of the image seen at these viewing subzones by taking the
      inverse of the number of different view images patched together at different
      subzones. Although the combined viewing zone can be extended to almost all of the
      front space of the imaging system, in reality it is limited mainly by the image
      quality.

PMID- 15468699
TI  - Spatial carrier-fringe pattern analysis by means of wavelet transform: wavelet
      transform profilometry.
AB  - We present an analysis of a spatial carrier-fringe pattern in three-dimensional
      (3-D) shape measurement by using the wavelet transform, a tool excelling for its
      multiresolution in the time- and space-frequency domains. To overcome the
      limitation of the Fourier transform, we introduce the Gabor wavelet to analyze
      the phase distributions of the spatial carrier-fringe pattern. The theory of
      wavelet transform profilometry, an accuracy check by means of a simulation, and
      an example of 3-D shape measurement are shown.

PMID- 15468700
TI  - Comparison of conoscopic, telescopic, and goniometric methods for measuring
      angular emissions from medical liquid-crystal displays.
AB  - Although emissive displays exhibit a quasi-Lambertian emission, the anisotropy of
      the electro-optic effect that controls light transmission in liquid-crystal
      displays (LCDs) causes the pixel luminance to vary, sometimes strongly, with the
      viewing angle. These variations are not identical for all gray levels and can
      eventually cause gray-scale inversions. We compare methods currently used to
      measure angular luminance variations in the LCDs: the goniometric method, the
      telescopic method, and the conoscopic or Fourier-optics method. We show that,
      although they are the same at the high end of the gray scale, the results of the
      three methods differ significantly at lower gray levels. In some cases the
      measured luminance was as much as 38% higher for the conoscopic system, and 26%
      higher for the telescopic method, than the value obtained with the goniometric
      approach. This shift in the minimum luminance measurement translates directly
      into the contrast ratio, affecting the reporting of technical specifications of
      display systems.

PMID- 15468701
TI  - In-plane switching of cholesteric liquid crystals for visible and near-infrared
      applications.
AB  - We have investigated the in-plane switching of cholesteric liquid crystals for
      reflective wavelength shifters for visible and near-infrared applications. These
      devices are based on the elongation of the cholesteric pitch by an electric field
      perpendicular to the helical axis. The transmission notch-reflection peak
      position can be tuned continuously to a longer wavelength (redshift) by
      application of an in-plane electric field. The helix is completely unwound when
      the electric field is higher than the cholesteric-to-nematic transition field,
      and the sample is transformed to a transparent state. We have investigated the
      electro-optic performance of in-plane switching of cholesteric samples and
      developed a simple phenomenological model to describe the underlying electro
      optic phenomena.

PMID- 15468702
TI  - Effect of dopant composition ratio on nonvolatile holographic recording in
      LiNbO3:Cu:Ce crystals.
AB  - The effect of dopant composition ratio on nonvolatile holographic recording in
      LiNbO3:Cu:Ce crystals is investigated experimentally. The results show that the
      dopant composition ratio affects the recording sensitivity and fixed diffraction
      efficiency by altering the UV light absorption characteristics of the crystals
      during nonvolatile, holographic recording. Increasing the dopant composition
      ratio of Cu and Ce leads to an increase in the absorption of UV light and further
      to an increase in the recording sensitivity and fixed diffraction efficiency. The
      UV light absorption characteristics of LiNbO3:Cu:Ce crystals and their roles in
      nonvolatile holographic recording are theoretically analyzed. The theoretical
      results are consistent with those of the experiments.

PMID- 15468703
TI  - Evaluation by Monte Carlo simulations of the power limits and bit-error rate
      degradation in wavelength-division multiplexing networks caused by four-wave
      mixing.
AB  - Fiber nonlinearities can degrade the performance of a wavelength-division
      multiplexing optical network. For high input power, a low chromatic dispersion
      coefficient, or low channel spacing, the most severe penalties are due to four
      wave mixing (FWM). To compute the bit-error rate that is due to FWM noise, one
      must evaluate accurately the probability-density functions (pdf) of both the
      space and the mark states. An accurate evaluation of the pdf of the FWM noise in
      the space state is given, for the first time to the authors' knowledge, by use of
      Monte Carlo simulations. Additionally, it is shown that the pdf in the mark state
      is not symmetric as had been assumed in previous studies. Diagrams are presented
      that permit estimation of the pdf, given the number of channels in the system.
      The accuracy of the previous models is also investigated, and finally the results
      of this study are used to estimate the power limits of a wavelength-division
      multiplexing system.

PMID- 15468704
TI  - Performance effect in optical-communication systems caused by phase ripples of
      dispersive components.
AB  - We develop a simple theory that relates the performance of an optical component
      to the variance of the amplitude of its phase ripple that has been weighted by
      the incoming signal spectrum. Comparisons of model predictions for chirped fiber
      gratings with 10-Gbit/s test-bed simulations and measurements agree.

PMID- 15468705
TI  - Compact optical system for pulse-to-pulse laser beam quality measurement and
      applications in laser machining.
AB  - Fluctuations in beam quality (M2) have been observed on a pulse-to-pulse basis
      from an industrial Nd:YAG laser. This was achieved with a compact multiplane
      imaging method incorporating quadratically distorted diffraction gratings, which
      enabled simultaneous imaging of nine planes on a single CCD array. With this
      system, we measured across a range of beam qualities with an associated error (in
      M2 variation) of the order of 0.7%. Application of the system to fiber-optic beam
      delivery and laser drilling is demonstrated.

PMID- 15468706
TI  - Improvement of the self-Q-switching behavior of a Cr:LiSrAlF6 laser by use of
      binary diffractive optics.
AB  - It has been shown experimentally and theoretically that Q-switching behavior is
      possible in a flashlamp-pumped Cr-doped LiSrAlF6 (Cr3+:LiSAF) laser that consists
      only of two mirrors, a laser crystal, and a diaphragm. We demonstrate that
      insertion into a laser of a binary diffractive optical element can speed up the
      dynamics of the self-Q-switched laser such that the output pulse is shortened
      (from 60 to 33 ns) and its energy is increased (from 36 to 54 mJ). The self-Q
      switching behavior of the laser has the ability to produce a laser pulse with a
      duration that one can adjust continuously from 60 to 700 ns just by opening the
      diaphragm.

PMID- 15468707
TI  - Production of high-order Bessel beams with a Mach-Zehnder interferometer.
AB  - A new experimental setup is demonstrated to produce high-order Bessel beams. It
      is based on the field decomposition of the Bessel beam into its even and odd
      field components. The implementation is performed over the spectral components
      with a Mach-Zehnder interferometer that synthesizes the components into the
      desired Bessel beam. The main advantage of our setup is that the required annular
      transmittances have only discrete phase changes of pi radians instead of a
      continuous change of phase.

PMID- 15468708
TI  - Narrow-linewidth megahertz-rate pulse-burst laser for high-speed flow
      diagnostics.
AB  - A second-generation pulse-burst laser system for high-speed flow diagnostics is
      described in detail. The laser can produce a burst of high-energy pulses (of the
      order of hundreds of millijoules per pulse) with individual pulse durations of
      less than 10 ns and pulse separations as short as 1 micros. A key improvement is
      the addition of a phase-conjugate mirror, which effectively isolates the high
      intensity, short-duration pulses from the low-intensity, long-duration background
      illumination. It allows for more-efficient amplification and harmonic generation,
      with efficiencies exceeding 50% for second-harmonic and 40% for third-harmonic
      generation. Characteristics of the laser system, including gain narrowing, pulse
      burst energy distribution, pulse narrowing, and overall pulse-burst energy, are
      described. In addition, the applicability of the laser for spectroscopic-based
      flow diagnostics is demonstrated through the presentation of megahertz-rate
      planar Doppler velocimetry results.

PMID- 15468709
TI  - Amplified spontaneous emission and gain from optically pumped films of dye-doped
      polymers.
AB  - The amplified spontaneous emission and gain characteristics of various
      fluorescent dyes, 2-(1,1-dimethylethyl)-6(2-(2,3,6,7-tetrahydro-1,1,7,7
      tetramethyl-1H,5H-benzo[ij] quinolizin-9-1)ethenyl)-4H-pyran-4-ylidene)
      propanedinitrile (DCJTB) and 4-dicyanomethylene-2-methyl-6-(p-dimethyl
      aminostyryl)-4H-pyran (DCM), doped in polystyrene (PS) matrices were studied and
      compared. It was found that DCJTB has a larger net gain, 40.72 cm(-1), a lower
      loss, 2.49 cm(-1), and a lower threshold, 0.16 (mJ/ pulse)/cm2, than DCM, which
      has a net gain of 11.95 cm(-1), a loss of 9.25 cm(-1), and a threshold of
      4(mJ/pulse)/cm2. The improvement of performance in DCJTB PS films is attributed
      to the larger free volume of DCJTB caused by the introduction of steric spacer
      groups into the DCJTB molecule.

PMID- 15468710
TI  - Electro-optic modulator capable of generating simultaneous amplitude and phase
      modulations.
AB  - We report on the analysis and prototype characterization of a dual-electrode
      electro-optic modulator that can generate both amplitude and phase modulations
      with a selectable relative phase, termed a quadrature variable modulator (QVM).
      All modulation states can be reached by tuning only the electrical inputs,
      facilitating real-time tuning, and the device has shown good suppression and
      stability properties. A mathematical analysis is presented, including the
      development of a geometric-phase representation for modulation. The experimental
      characterization of the device shows that relative suppressions of 38, 39, and 30
      dB for phase, single sideband, and carrier-suppressed modulations, respectively,
      can be obtained as well as that the device is well behaved when scanning
      continuously through the parameter space of modulations. The QVM is compared with
      existing optical configurations that can produce amplitude and phase-modulation
      combinations in the context of applications such as the tuning of lock points in
      optical-locking schemes, single-sideband applications, modulation fast-switching
      applications, and applications requiring combined modulations.

PMID- 15468711
TI  - Coherent differential absorption lidar measurements of CO2.
AB  - A differential absorption lidar has been built to measure CO2 concentration in
      the atmosphere. The transmitter is a pulsed single-frequency Ho:Tm:YLF laser at a
      2.05-microm wavelength. A coherent heterodyne receiver was used to achieve
      sensitive detection, with the additional capability for wind profiling by a
      Doppler technique. Signal processing includes an algorithm for power measurement
      of a heterodyne signal. Results show a precision of the CO2 concentration
      measurement of 1%-2% 1sigma standard deviation over column lengths ranging from
      1.2 to 2.8 km by an average of 1000 pulse pairs. A preliminary assessment of
      instrument sensitivity was made with an 8-h-long measurement set, along with
      correlative measurements with an in situ sensor, to determine that a CO2 trend
      could be detected.

PMID- 15468712
TI  - Single-shot, two-dimensional ballistic imaging through scattering media.
AB  - Imaging through scattering materials is an important research area that is
      generally limited to medical diagnostic applications. Published techniques
      typically use a method of time- or coherence-gating of ballistic photons that
      separates these early photons in order to acquire an image without the large
      background created by the later-arriving diffuse light. Because of the limited
      number of ballistic photons and the typically low signal-to-noise ratios of these
      schemes, a large number of averages or scans is necessary. If the desired image
      is changing rapidly, however, single images of this transient are required. We
      have therefore evaluated a two-dimensional, single-shot method that can be used
      for imaging rapid transients in scattering environments.

PMID- 15468713
TI  - Single-particle sizing from light scattering by spectral decomposition.
AB  - A Fourier transform was applied to size an individual spherical particle from an
      angular light-scattering pattern. The position of the peak in the amplitude
      spectrum has a strong correlation with the particle size. A linear equation
      retrieved from regression analysis of theoretically simulated patterns provides a
      relation between the particle size and the location of the amplitude spectrum's
      peak. The equation can be successfully applied to characterize particles of size
      parameters that range from 8 to 180 (corresponding to particle sizes that range
      from 1.2 to 27.2 microm at a wavelength of 0.633 microm). The precision of
      particle sizing depends on the refractive index and reaches a value of 60 nm
      within refractive-index region from 1.35 to 1.70. We have analyzed four samples
      of polystyrene microspheres with mean diameters of 1.9, 2.6, 3.0, and 4.2 microm
      and a sample of isovolumetrically sphered erythrocytes with a scanning flow
      cytometer to compare the accuracy of our new method with that of others.

PMID- 15468714
TI  - Measurements of absolute CH concentrations by cavity ring-down spectroscopy and
      linear laser-induced fluorescence in laminar, counterflow partially premixed and
      nonpremixed flames at atmospheric pressure.
AB  - We report quantitative, spatially resolved measurements of methylidyne
      concentration ([CH]) in laminar, counterflow partially premixed and nonpremixed
      flames at atmospheric pressure by using both cavity ring-down spectroscopy (CRDS)
      and linear laser-induced fluorescence (LIF) in the A-X (0, 0) band. Three
      partially premixed (phiB = 1.45, 1.6, 2.0) flames plus a single nonpremixed
      methane-air flame are investigated at a global strain rate of 20 s(-1). These
      quantitative measurements are compared with predictions from an opposed-flow
      flame code when utilizing two GRI chemical kinetic mechanisms (versions 2.11 and
      3.0). The LIF measurements of [CH] are corrected for variations in the electronic
      quenching rate coefficient by using predicted major species concentrations and
      temperatures along with quenching cross sections for CH that are available in the
      literature. The peak CH concentration obtained by CRDS is used to calibrate the
      quenching-corrected LIF measurements. Excellent agreement is obtained between CH
      concentration profiles measured by using the CRDS and LIF techniques. The spatial
      location of the CH layer is very well predicted by GRI 3.0; moreover, the
      measured and predicted CH concentrations are in good agreement for all the flames
      of this study.

PMID- 15468715
TI  - [Primary bacterial endocarditis (Part 1)].

PMID- 15468716
TI  - [A role of the endothelium in the development of pulmonary hypertension in
      patients with chronic obstructive lung diseases].

PMID- 15468717
TI  - [A role of activation of proinflammatory cytokines and production of autoimmune
      complexes in the pathogenesis of chronic heart failure in patients with
      postinfarct cardiac dysfunction].
AB  - A comparative randomized clinical study was conducted to evaluate the diagnostic
      and prognostic value of the activation of proinflammatory cytokines [tumor
      necrosis factor-alpha (TNF-alpha), interleukin (IL)-1alpha, IL-2, IL-6, IL-8)]
      and the increased production of autoimmune complexes in the pathogenesis of
      chronic heart failure (CHF) in patients with coronary heart disease (CHD). The
      study included 47 patients with CHD who had a more than 6-month history of Q
      forming myocardial infarction. The patients were randomized into 3 groups: 1) 21
      patients with NYHA Functional Class (FC) II heart failure (HF); 2) 16 patients
      with FC III HF; and 3) 10 with FC IV HF. Basic therapy involved angiotensin
      converting enzyme (ACE) inhibitors, nitrates, diuretics, beta-adrenoblockers;
      27.6% received digoxin, disaggregatory agents. A study protocol involved the
      estimation of the parameters of EchCG, paired bicycle ergometric tests, 6-min
      walking test, ECG daily monitoring, the levels of proinflammatory cytokines in
      the serum and IgG autoantibodies to cardiolipin. The findings suggest that with
      the higher expression of autoimmune complexes, the activation of cytokines
      (primarily TNF-alpha, IL-1alpha, IL-2) plays an important role in the
      pathogenesis of CHF in patients with postinfarct cardiac dysfunction: the high
      activation of cytokines and the elevated level of autoimmune complexes are
      associated with moderate or severe NYHA FC II-IV HF, depressed left ventricular
      contractility (ejection fraction, 23-38%), low exercise tolerance, and cardiac
      remodeling.

PMID- 15468718
TI  - [The incidence and pattern of cardiac rhythm and conduction disturbances in
      patients with different clinical and pathogenetic types of hypertensive disease].
AB  - In 237 patients with grades I-III hypertensive disease, the incidence and pattern
      of cardiac rhythm and conduction disturbances were studied in various clinical
      and pathogenetic types of the disease. By taking into account the known clinical,
      laboratory, and hemodynamic criteria, the patients were profiled by the following
      types: 62 (26.2%) patients with a hyperadrenergic type, 61 (25.7%) with a
      hyperhydration types, 60 (25.3%) with a hyperrenin type, and 54 (22.8%) with a
      calcium-dependent type. Bicycle ergometric exercise test, daily ECG monitoring,
      and a transesophageal electrophysiological study of the heart were performed to
      detect latent, routine ECG-unverified cardiac rhythm and conduction disturbances.
      In the total group of patients, cardiac arrhythmia and block occurred in 55.3% of
      the cases, including in 55.7% they are latent. Cardiac rhythm disturbances were
      most frequently detected in the hyperadrenergic and hyperrenin variants of the
      disease (50.0 and 43.3%, respectively). Premature beats and paroxysmal
      supraventricular tachyarrhythmias were predominantly diagnosed in the
      hyperadrenergic type of HD; intraventricular conduction disturbances and
      extrasystolic arrhythmia were in the hyperhydration type; the sick sinus syndrome
      and atrioventricular blocks were in the hyperrenin type. The above cardiac rhythm
      and conduction disturbances were equally characteristic for the calcium-dependent
      type of the disease. There was a direct correlation between the detection rate of
      cardiac arrhythmia and block and the degree of a risk for cardiac and cerebral
      events, as well as left ventricular hypertrophy. Thus, the study of the incidence
      and pattern of cardiac arrhythmias associated with hypertensive disease is of
      importance for choosing an effective and safe treatment; and their existence
      should be borne in mind to stratify a risk of prognosis.

PMID- 15468719
TI  - [The specific features of circadian blood pressure variations in patients with
      hypertensive disease in different types of weather].
AB  - The specific features of circadian blood pressure (BP) variations were studied in
      162 patients aged 20 to 60 years who had hypertensive disease (HD) in the warm
      period of a year in different types of weather. In accordance with the type of
      weather in which daily BP monitoring (DBPM) was performed, the examinees were
      divided into 2 groups: 1) those examined in droughty (anticyclonic) weather; 2)
      those examined in moist (cyclonic) weather, The groups were matched by the number
      (81) of patients, age, gender, duration of the disease, and office BP values. The
      mean BP during a day, daylight and night hours, the maximum and minimum BP during
      wake and sleep was significantly high in moist weather. Examining the magnitude
      of a nocturnal BP decrease indicated that in Group 1, its adequate decrease (the
      dipper daily curve) was recorded in 72.3% of the patients; inadequate BP decrease
      (the non-dipper daily curve) was in 24.2%; paradoxical nocturnal hypertension
      (night peaker) was seen in 1.8%. In Group 2, adequate and inadequate nocturnal BP
      decreases were observed in 44.4 and 41.3%, respectively; paradoxical nocturnal
      hypertension was in 7.7%. Statistical processing confirmed the validity of the
      findings. Moist (cyclonic) weather was ascertained to be marked by the changes in
      adequate circadian BP variations: a significant mean daily, maximum, and minimum
      systolic BP (SBP) and diastolic BP (DBP), as well as by the inadequate nocturnal
      lowering of SBP and DBP, which determines a poor prognosis and may serve as a
      basis for preventing HD complications in this period of a year.

PMID- 15468720
TI  - [Experience with spiral computed tomography used in the diagnosis of
      atherosclerotic calcification of coronary arteries].
AB  - Cardiovascular diseases, including coronary heart disease (CHD), are one of the
      main causes of death in persons aged above 40 years. The WHO report of human
      health in 2003 declares cardiovascular diseases as an occult epidemiology of not
      only the developed, but also developing countries. CHD prevention successfully
      tested in the USA and Europe is recognized to be the only method of its control.
      The standardized calculation of coronary calcification (Cardiac Scoring) is one
      of the most constituents of this prevention. Cardiac Scoring was first used
      during electronic radiation tomography in 1990. While algorithms of a study and
      clinical use of the results were produced, X-ray computed tomographs, both single
      spiral (SSCT) and multispiral (MSCT) ones were perfected. The experience with
      Cardiac Scoring was successfully applied to the use of MSCT. Although routine
      spiral tomography ranks below MSCT in its capacity of visualizing the distal
      segments of coronary arteries and of synchronizing with the movement of the
      heart, SSCT has some advantages for its wide use, accessibility, and rather high
      efficiency. Demand for primary, ambulatory screening for coronary
      atherosclerosis, primarily asymptomatic one when the typical symptom complex of
      CHD has not been formed yet generates the necessity of using all possible methods
      for calculation of calcification, including spiral computed tomography. The
      determination of coronary calcification by SSCT and MSCT is under discussion,
      this problem has its supporters and opponents. At the same time it is accepted
      that it would near sightedly suppress innovation that may be finally
      advantageous.

PMID- 15468721
TI  - [Structural and functional reconfiguration of large arteries in hypertensive
      disease: a role of connective tissue metabolic disturbances].
AB  - The study was undertaken to define a role of connective tissue metabolism (CTM)
      in the structural and functional changes of arterial vessels in patients with
      hypertensive disease (HD). Eighty-nine patients with HD and 33 apparently healthy
      individuals were examined. The morphometrical parameters of the aorta were
      studied by magnetic resonance imaging (MRI), external and internal diameters (ED
      and ID, respectively) and the thickness of the wall (Hao) at the level of the
      ascending aorta and its mass (Mao) were determined. To evaluate aortic function,
      the authors made Doppler studies and determined aortic pulse wave velocity (APWV)
      and the aortic rigidity coefficient (RC). CTM was evaluated by the serum content
      of free oxyproline (FOP) and peptide-bound oxyproline (PBOP), type I procollagen
      C propeptides (PCPP), circulating antibodies (Cab) to elastin, and by the urinary
      levels of total glycosaminoglycans (TGAG) and sulfated glycosaminoglycans (SGAG).
      The patients with HD were found to have significantly higher levels of ID, ED,
      Hao Mao, APWV, RC, which is indicative of dilatation of the aorta and the
      increased thickness and rigidity of its wall. Patients with HD showed
      statistically significant serum elevated levels of PBOP and type I PCPP, a
      decrease in CAb to elastin, and increased urinary content of TGAG and SGAG, which
      indicates the activated synthesis of collagen and structural proteoglycans and
      the degradation of elastin in HD. The results of a multiple regression analysis
      demonstrated a role of CTM changes as a significant and independent factor that
      determines structural and functional impairments of large arteries in patients
      with HD.

PMID- 15468722
TI  - [Platelet aggregatory impairments in chronic obstructive bronchitis and a role of
      laser therapy in their correction].
AB  - A comparative follow-up was made to study platelet aggregatory function in
      patients with chronic obstructive bronchitis (COB) prior to and following
      treatment. The patients were divided into study and control groups. In addition
      to conventional treatment, the patients of the study group received laser therapy
      as intravenous blood irradiation. According to the type of baseline platelet
      aggregatory changes, all the patients were divided into 3 subgroups: 1) patients
      with hyperaggregation; 2) those with normal aggregation; and 3) those with
      hypoaggregation. In the patients from the study group, the performed treatment
      corrected platelet aggregatory disorders--the degree of aggregation decreased
      from 78 +/- 8.6% to 56.8 +/- 6.9% in Subgroup 1, increased from 23 +/- 4.8% to
      54.6 +/- 6.21% in Subgroup 3. The similar positive changes in aggregation rates
      and the cumulative aggregation index was observed in the study group. In the
      control group, conventional drug therapy caused no substantial changes in
      platelet aggregatory function. Thus, intravenous blood laser irradiation is an
      effective technique in correcting thrombocytic dysfunction in COB.

PMID- 15468723
TI  - [A role of lipid peroxidation in postoperative impairments of thrombocytic
      hemostasis in patients with lung cancer].
AB  - The paper analyzes the time course of changes in spontaneous platelet aggregation
      (SPA), malonic dialdehyde (MDA) levels, and overall blood antioxidative capacity
      in the sera of patients with lung cancer after surgical treatment. The laboratory
      signs of impaired lipid peroxidation are shown to form by postoperative days 7 to
      14. Depletion of the activity of antioxidants is followed by the elevated blood
      levels of MDA and may an additional factor of enhanced SPA. The use of
      antioxidants on postoperative days 7 to 14 will assist in avoiding the depletion
      of the antioxidative system. The efficiency of this therapy may be evaluated from
      SPA.

PMID- 15468724
TI  - [Clinical and immunological characteristics of primary and secondary
      antiphospholipid syndrome].
AB  - A prospective study was made of 93 patients with antiphospholipid syndrome (APS),
      including 34 patients with primary APS (PAPS) and 59 with secondary APS (SAPS)
      associated with exanthematous lupus erythematosus (ELE). According to the
      clinical outcomes, PAPS is heterogeneous since the clinical and laboratory signs
      of ELE or lupus-like syndrome occurred in two thirds of the patients with PAPS.
      The clinical manifestations of PAPS and ELE-associated SAPS differed at the
      height of disease: the signs of vascular diseases were prevalent in patients with
      PAPS and ELE-associated systemic manifestations were predominant in those with
      SAPS. In the patients with APS who further developed ELE, unlike those with PAPS
      showed a high incidence of transient erythema and arthralgias. The levels of
      serological markers in patients with APS at its height did not differ. As
      compared with healthy individuals, patients with APS were found to have the
      similar changes in the nonspecific immunological parameters manifested by
      absolute lymphopenia, by the diminished Fc-phagocytosis of monocytes and
      neutrophils, by the elevated levels of circulating immune complexes, and by the
      high biocidal activity of neutrophils. There were no significant differences in
      the immunity of patients with PAPS and in those with SAPS.

PMID- 15468725
TI  - [Clinical features and physical fitness parameters in athletes with cardiac
      connective tissue dysplasia syndrome].
AB  - Seventy-seven athletes with different manifestations of the cardiac connective
      tissue dysplasia (CCTD) syndrome (mitral prolapse (MP), anomalously located
      chordae (ALC) of the left ventricle and/or their combination) and 23 athletes
      without signs of CCTD syndrome were examined. The purpose of the study was to
      determine the specific features of the phenotypic picture, ECG data, and physical
      fitness in athletes with the manifestations of CCTD syndrome. The characteristic
      features of anthropometric data (higher heights and decreased body mass index), a
      larger number of the phenotypic signs of CCTD, the specific features of ECG, and
      lower parameters of physical fitness and aerobic capacities in the groups of MP,
      ALC, and/or their combination were identified; the impact of MP and ALC on these
      parameters was evaluated.

PMID- 15468726
TI  - [The specific features of the course of chronic viral hepatitis concurrent with
      chronic opisthorchiasis].
AB  - A hundred and one patients with chronic viral hepatitis (CVH) in the phase of
      replication were examined. Group 1 comprised 53 patients with CVH in combination
      with chronic opisthorchiasis. Group 2 (a comparison group) included 48 patients
      with CVH without opisthorchiasis. According to the etiology of hepatitis, each
      group was divided into 3 subgroups: subgroups 1a and 2a consisted of patients
      with CVHB; 1b and 2b included those with CVHC, and 1c and 2c comprised those with
      CVHB+C. The clinical, functional, and morphological status of the liver was
      studied and hepatic tissue was qualitatively and quantitatively assessed in all
      the examinees. The findings suggest that Opisthorchis is an additional factor
      that aggravates hepatic damage in patients with CVH in the replicative phase of
      infection.

PMID- 15468727
TI  - [Retrospective analysis of the morphological, cytochemical, cytogenetic, electron
      microscopic, and biochemical features of blast cells in acute promyelocytic
      leukemia].
AB  - The paper presents a retrospective analysis of long-term follow-ups (from 1959 to
      2000) of 86 patients with acute pro-myelocytic leukemia, a rare type of
      hemoblastoses. The specific features of this form of leukemia is that blast cells
      of the bone marrow and peripheral blood have a specific granularity that plays a
      decisive role in the development of the severe hemorrhagic syndrome leading to
      patients' death. The morphological, cytochemical, cytogenetic, electron
      microscopic, and biochemical features of blast cells in this disease and its
      pathogenesis, clinical presentation, and treatment are considered. An extract
      from the records of a female patient who has had a complete clinical and
      hematological remission for 22 years is given. The follow-up of such a prolonged
      remission has not been covered in the Russian literature.

PMID- 15468728
TI  - [Experience with the superselective third-generation beta-adrenoblocker nebivolol
      used to treat patients with prior myocardial infarction].
AB  - The effectiveness and safety of therapy with nebivolol and its effects on life
      quality (LQ) were studied in 71 patients with prior myocardial infarction (MI)
      with an ejection fraction of 40% or more. The follow-up lasted 1 year. The mean
      daily dose of the drug was 3.66 +/- 0.11 mg. Echocardiography, bicycle ergometry,
      daily ECG monitoring, survey according to the questionnaires developed by V. P.
      Zaitsev, a researcher of All-Russian Cardiology Research Center, Russian Academy
      of Medical Sciences, to the depression scale (DS), the personality scale (PS) and
      reactive anxiety scale (RAS) by Spilberg-Khanin were performed. The study was
      conducted on the day of initiation of outpatient treatment, following 3 months
      and 1 year. After 3 months of therapy, clinical improvement was observed in 83%
      of the patients and it preserved at the same level till the end of the first
      year: exercise tolerance and the total volume of work increased significantly (p
      < 0.001), 97% of the examinees returned to work. Nebivolol produced an
      antiarrhythmic effect in 66.7% of the patients with high Lown gradation premature
      beats. Therapy with the agent showed a low mortality rates (1.4%), few number of
      cardiovascular excesses (4.2%), and good tolerability (7.2%). By the end of the
      first year, cardiac remodeling improved insignificantly: end-systolic volume, end
      diastolic volume, left ventricular myocardial mass decreased by 6.4, 1.4, and 7%,
      respectively; fraction ejection increased by 2.3% of the baseline values. The
      parameters of LQ improved: the RAS scores reduced by 18.4%; the number of
      patients with high PS scores decreased significantly (p < 0.05) due to the
      increase in the number of patients with its moderate level (p < 0.01) and, what
      is significant, erectile function did not deteriorate. Thus, nebivolol
      demonstrated its high effectiveness and safety during prolonged therapy of
      patients with prior MI, without cardiodepressive activity and favorable impact on
      their LQ.

PMID- 15468729
TI  - [Present-day classification and nomenclature of rheumatic fever].
AB  - The paper presents a new classification of rheumatic fever, which has been
      adopted by the Plenary Session of the Association of Rheumatologists of Russia in
      May 2003. This classification envisages the abandonment of the term "rheumatism"
      in its former interpretation. The term "acute rheumatic fever" (ARF) appears to
      be more justified since it makes a physician elucidate its association with Group
      A streptococcal infection of the throat and prescribe antibiotics for eradication
      of this infection in its acute period (primary prophylaxis) and for prevention of
      repeated attacks (secondary prophylaxis). The current interpretation of the
      clinical syndromes/symptoms and laboratory parameters that enter into diagnostic
      criteria for ARF is presented. There are 2 types of outcome of the disease. In
      case of recovery, we are dealing with the complete regression of the clinical
      symptomatology of ARF, normalized laboratory parameters and no residual changes.
      Chronic rheumatic diseases of the heart are considered to mean a disease
      characterized by a cardiac valvular lesion as postinflammatory marginal fibrosis
      of valvular leaflets or cardiac abnormality (failure and/or stenosis) developed
      after prior ARF. Emphasis is laid on the significance of evidence of Group A
      streptococcal infection that precedes the development of the disease. Examples of
      clinical diagnosis in accordance with the terminology of the International
      Classification of Diseases, the 10th edition, are given in the paper.

PMID- 15468730
TI  - [Itching in systemic diseases. 1. Causes and mechanisms].

PMID- 15468731
TI  - [Differential diagnosis of eosinophilia in combination with intoxication
      syndrome].

PMID- 15468732
TI  - [E. M.Tareev's clinical approaches to the problem of the so-called collagenoses].

PMID- 15468733
TI  - The emergence of temporal hyperacuity from widely tuned cell populations.
AB  - Typically, individual neural cells operate on a millisecond time scale yet
      behaviorally animals reveal sub-microsecond acuity. Our model resolves this huge
      discrepancy by using populations of many widely tuned cells to attain sub
      microsecond resolution in a temporal discrimination task. An echolocating bat
      uses its auditory system to locate objects and it demonstrates remarkable
      temporal precision in psychophysical tasks. Auditory cells were simulated using
      realistic parameters and connected in three ascending layers with descending
      projections from auditory cortex. Coincidence detection of firing collicular
      cells at thalamus and subsequent integration of multiple inputs at cortex,
      produce an estimate of time represented as the mean of the active cortical
      population. Multiple estimates allow the model bat to use memory to recognize
      predictable change in stimuli values. The best performance is produced using
      cortical feedback and a computation of target time based on combining the current
      and previous estimates. Temporal hyperacuity is attained through population
      coding of physiologically realistic cells but depends on the inherent properties
      of the psychophysical task.

PMID- 15468734
TI  - Motion detection and prediction through spike-timing dependent plasticity.
AB  - We describe a possible mechanism for the formation of direction- and velocity
      selective cells in visual cortex through spike-timing dependent learning. We
      contrast the case where only feedforward excitation and inhibition signals are
      provided to visual neurons with the case where both feedforward and feedback
      signals are provided. In the feedforward-only case, neurons become selective for
      a broad range of velocities centered around the training velocity. However, we
      show that direction selectivity in this case is strongly dependent on delayed
      feedforward inhibition and in contrast to experimental results, becomes
      dramatically weaker when inhibition is reduced. When feedback connections are
      introduced, direction selectivity becomes much more robust due to predictive
      delays encoded in recurrent activity. Direction selectivity persists in the face
      of decreasing inhibition in a manner similar to experimental findings. The model
      predicts that direction-selective cells should exhibit anticipatory activity due
      to recurrent excitation and suggests a pivotal role for spike-timing dependent
      plasticity in shaping cortical circuits for visual motion detection and
      prediction.

PMID- 15468735
TI  - Neural network model to generate head swing in locomotion of Caenorhabditis
      elegans.
AB  - Computer simulation of the neural network composed of the head neurons of
      Caenorhabditis elegans was performed to reconstruct the realistic changes in the
      membrane potential of motoneurons in swinging the head for coordinated forward
      locomotion. The model neuron had ion channels for calcium and potassium, whose
      parameters were obtained by fitting the experimental data. Transmission
      properties of the chemical synapses were set as graded. The neural network
      involved in forward movement was extracted by tracing the neuronal activity flow
      upstream from the motoneurons connected to the head muscles. Simulations were
      performed with datasets, which included all combinations of the excitatory and
      inhibitory properties of the neurons. In this model, a pulse input entered only
      from motoneuron VB1, and activation of the stretch receptors on SAA neurons was
      necessary for the periodic bending. The synaptic output property of each neuron
      was estimated for the alternate contraction of the dorsal and ventral muscles.
      The AIB neuron was excitatory, RIV and SMD neurons seemed to be excitatory and
      RMD and SAA neurons seemed to be inhibitory. With datasets violating Dale's
      principle for the SMB neuron, AIB neuron was excitatory and RMD neuron was
      inhibitory. RIA, RIV and SMD neurons seemed to be excitatory.

PMID- 15468736
TI  - Making connections in a high-tech world.

PMID- 15468737
TI  - A teenager's view of rehabilitation.

PMID- 15468738
TI  - Are you a lifelong learner?

PMID- 15468739
TI  - Therapeutic positioning, wheelchair seating, and pulmonary function of children
      with cerebral palsy: a research synthesis.
AB  - This review analyzed research literature concerning pulmonary function and
      positioning of persons with cerebral palsy (CP) who lack trunk control. The
      search reviewed literature published from 1966 through March 2003. Twenty-eight
      references located by electronic database search were analyzed using Moody's
      Research Analysis Tool. All reflected either a physiologic or therapy-based model
      involving function in activities of daily living, but no health outcomes. One
      reference applied a nursing model to care of developmentally disabled persons,
      including those with CP. Existing research gaps include the need for human
      subjects, larger sample sizes, measurement of influence of gravity on body
      position, greater precision in describing independent variables of positioning,
      and participation by children with disabilities. This paper proposes a conceptual
      model using Orem's self-care theory upon which to base nursing interventions,
      including therapeutic positioning of persons with CP who lack trunk control.
      Future nursing research should explore health outcomes of various properties of
      wheelchair positioning.

PMID- 15468740
TI  - Determinants of discharge destination for stroke patients.
AB  - Discharge to community is an important outcome measure for rehabilitation
      facilities. Studies consistently find that stroke patients with higher scores on
      the Functional Independence Measure (FIM) are more likely to be discharged to the
      community. Other variables, including age, gender, and living status, also have
      shown a relationship to discharge destination for stroke patients. This study
      explored the differences between stroke patients who were discharged to the
      community and those who were discharged to a nursing home after a stay on an
      acute inpatient rehabilitation unit. Results indicated that older patients and
      those with lower admission FIM scores are more likely to be discharged to nursing
      homes, but many patients who fit this profile are discharged to the community.
      The main destination determinant was how well a patient's need for care matched
      informal caregiving resources. These findings indicate a need for additional
      focused assessment of available care giving resources.

PMID- 15468741
TI  - I am not alone: spirituality of chronically ill rural dwellers.
AB  - Spirituality plays a vital role in adjusting to chronic illness and
      rehabilitation nurses strive to gain understanding of their patients'
      spirituality in order to improve patient care and outcomes. The purpose of this
      qualitative study was to explore the nature of spirituality in chronically ill
      rural dwellers and how it relates to their illness. As a part of this pilot
      project, 10 women with chronic illness volunteered to participate in a phone
      interview to discuss their spirituality. Content analysis was used to analyze the
      data. The theme Means the World to Me described what spirituality meant to
      participants. The following themes described how spirituality related to chronic
      illness: I Am Not Alone, Putting on a Happy Face, Others Are Worse Off,
      Transcending Despair and Letting Go. Participants were able to use spiritual
      coping measures to transcend despair. Results from this study provide
      rehabilitation nurses with insight into the spirituality needs of chronically ill
      rural-dwelling women.

PMID- 15468742
TI  - Effect of a computer-based intervention on social support for chronically ill
      rural women.
AB  - Social support is a key factor in illness management. Despite the positive
      effects of support groups, there are barriers to participation by rural dwellers
      in face-to-face groups. To address these barriers, a computer-based support group
      intervention, the Women to Women Project, was designed to provide peer support
      and health information through a computer-based intervention. Data from three
      groups (intervention, information, comparison) of woman who participated in the
      program were analyzed. The pattern of improvement in social support was in the
      anticipated direction, but not significant in the main analysis. Exploratory
      analysis was conducted on a vulnerable subsample of women reporting low social
      support and high psychosocial distress. Results suggest that improvement in
      social support, based on the intervention, was greater for the vulnerable
      subsample as compared with the sample as a whole. An effective and efficient
      means of providing social support and facilitating the mobilization of this
      support is through self-help groups; this study demonstrates that virtual support
      groups can increase perceived social support.

PMID- 15468743
TI  - Job experiences of personal assistants employed in a consumer-directed personal
      assistance services programs.
AB  - The demand for personal assistants for persons with disabilities is outpacing the
      supply. The objective of this pilot project was to describe the training and
      supervision needs of personal assistants, the nature of the assistant-consumer
      relationship, and the job satisfaction associated with being employed as a
      personal assistant. Telephone interviews were conducted with 24 personal
      assistants. All of the participants reported being competent and well trained in
      their work and 79% of the participants reported being very satisfied with their
      work as a personal assistant. All also reported they had an opportunity to
      accomplish something worthwhile in their jobs. Participants reported high levels
      of satisfaction with their relationship with their employers and with their jobs
      in general, despite dissatisfaction with low wages. Further research is needed to
      identify strategies for increasing the supply of personal assistants, who are
      pivotal to helping consumers maintain their independence.

PMID- 15468744
TI  - Substance abuse, suicidality, and self-esteem in South African adolescents.
AB  - Associations among six different domains of self-esteem (peers, school, family,
      sports/athletics, body image, and global self-worth) and risk behaviors related
      to substance use and suicidality were investigated in a sample of South African
      adolescents. Students enrolled in Grades 8 and 11 at independent secondary
      schools in Cape Town (N = 116) completed the Self-Esteem Questionnaire (SEQ) and
      a questionnaire that asked about their participation in a range of risk
      behaviors. Logistic regression analyses indicated that particular domains of self
      esteem were differentially associated with indicators of alcohol, cigarette and
      drug use and suicidal ideation or behaviors in adolescents. Family self-esteem
      showed the strongest overall pattern of associations with the risk behaviors.
      Overall, the findings of this study suggest that interventions which aim to
      protect adolescents from engaging in risk behaviors by increasing their self
      esteem are likely to be most effective and cost-efficient if they are aimed at
      the family and school domains.

PMID- 15468745
TI  - Who's calling the shots? Decision-makers and the adoption of effective school
      based substance use prevention curricula.
AB  - This study investigates the relative roles of school district and school-level
      decision-makers in the implementation of effective substance use prevention
      curricula. Drawing on a "Site-Based Management" approach to effective decision
      making, we hypothesized that schools whose personnel played active decision
      making roles would be more likely to implement effective curricula than those in
      which decision-making was the prerogative of school district personnel. Study
      data comprised 1369 questionnaires completed by a representative national sample
      of both district-level prevention coordinators and middle school-based lead
      prevention teachers. From the perspective of the lead prevention teachers, the
      school district-level prevention coordinator was more influential than school
      staff in selecting effective prevention curricula. However, we did find some
      support for our hypothesis from our district-level informants, who indicated that
      community groups and advisory committees also play a modest role in the selection
      of such curricula.

PMID- 15468746
TI  - Is screening and brief advice for problem drinkers by clergy feasible? A survey
      of clergy.
AB  - Routine screening for alcohol abuse in primary care, with brief advice to stop
      drinking for those screening positive, can detect individuals with alcohol
      problems and reduce alcohol use and alcohol induced problems in those detected.
      Not everyone with alcohol problems sees a physician regularly, however, and not
      all respond to a physician's brief advice. To explore the feasibility of
      expanding screening for alcohol problems to clergy, we did a mailed survey to 315
      clergy at Christian churches in Cleveland, Ohio. Clergy reported a variety of
      views about alcohol use and abuse, but most agreed that alcoholism is a disease.
      They indicated counseling a significant number of parishioners, and were
      receptive to learning brief screening questions to detect alcohol problems. We
      conclude that many clergy would be interested in a strategy of screening and then
      giving brief advice or referral to individuals found to have alcohol problems.

PMID- 15468747
TI  - Toward an ecstasy and other club drug (EOCD) prevention intervention for rave
      attendees.
AB  - A growing body of recent research has identified that "rave" attendees are at
      high risk for the use of "club drugs," such as 3,4-methylenedioxymethamphetamine
      (MDMA or "ecstasy"). Rave attendees, however, comprise only one of several club
      going populations. In the current study, we explore the prevalence of ecstasy and
      other club drug (EOCD) use among a sample of club attendees in Washington, DC.
      Data were collected from adult, primarily homosexual, club attendees during the
      summer of 2003. Data collection was scheduled between 11 p.m. and 3 a.m.
      Participation rates were high. Of the 211 club attendees approached, 88% (n =
      186) completed the interview. Drug use prevalence rates were low. With the
      exception of alcohol and marijuana, 2-day self-reports were less than 1% for each
      drug. These findings, amalgamated with results from other EOCD-related studies
      involving several distinct populations, offer considerable insight into the state
      of ecstasy in American society. Based on a meta-analysis of this literature, we
      offer a community-level prevention intervention for the population at highest
      risk for EOCD use-rave attendees.

PMID- 15468748
TI  - Comparison of web and mail surveys in collecting illicit drug use data: a
      randomized experiment.
AB  - This randomized experiment examined survey mode effects for self-reporting
      illicit drug use by comparing prevalence estimates between a Web-based survey and
      a mail-based survey. A random sample of 7,000 traditional-aged undergraduate
      students attending a large public university in the United States was selected to
      participate in the spring of 2001. Students were randomly assigned to self
      administer a survey via the Web or U.S. mail. The Web survey produced a
      significantly higher response rate than the U.S. mail survey. The prevalence
      estimates of illicit drug use (lifetime and past year) did not differ
      significantly between the two survey modes. The findings provide preliminary
      evidence that Web and U.S. mail surveys produce similar results regarding illicit
      drug use among undergraduate students. Although additional research is needed
      involving more diverse samples, these findings bode well for using Web surveys in
      college-based research.

PMID- 15468749
TI  - Say Yes First: follow up of a five-year rural drug prevention program.
AB  - Say Yes First--To Rural Youth and Family Alcohol/Drug Prevention (SYF) was a 5
      year, federally-funded U.S.D.H.H.S. Center for Substance Abuse Prevention (CSAP)
      project that involved 859 children in the class of the year 2000. The children in
      four rural school districts were followed from Grade 4 to Grade 8 from 1991 to
      1996. Initial results in a previous publication showed significant lower drug
      usage in this cohort than comparison students. A follow-up of 120 SYF
      participants and 136 comparison students in high schools using the National Youth
      Survey (Follow Up Questionnaire) indicated lower usage of alcohol, tobacco and
      other drugs for the program students and lower lifetime prevalence of marijuana
      use for program vs. comparison students. SYF students had higher course grades,
      lower school absenteeism, more positive attitudes toward school, less trouble in
      school and less negative self-appraisal. Program students also reported greater
      participation in sports, more family communication and fewer disagreements or
      arguments with their parents.

PMID- 15468750
TI  - Microarrays in pharmacogenomics.

PMID- 15468751
TI  - Some statistical and regulatory issues in the evaluation of genetic and genomic
      tests.
AB  - The genomics revolution is reverberating throughout the worlds of pharmaceutical
      drugs, genetic testing and statistical science. This revolution, which uses
      single nucleotide polymorphisms (SNPs) and gene expression technology, including
      cDNA and oligonucleotide microarrays, for a range of tests from home-brews to
      high-complexity lab kits, can allow the selection or exclusion of patients for
      therapy (responders or poor metabolizers). The wide variety of US regulatory
      mechanisms for these tests is discussed. Clinical studies to evaluate the
      performance of such tests need to follow statistical principles for sound
      diagnostic test design. Statistical methodology to evaluate such studies can be
      wide ranging, including receiver operating characteristic (ROC) methodology,
      logistic regression, discriminant analysis, multiple comparison procedures
      resampling, Bayesian hierarchical modeling, recursive partitioning, as well as
      exploratory techniques such as data mining. Recent examples of approved genetic
      tests are discussed.

PMID- 15468752
TI  - A generalized additive model for microarray gene expression data analysis.
AB  - Microarray technology allows the measurement of expression levels of a large
      number of genes simultaneously. There are inherent biases in microarray data
      generated from an experiment. Various statistical methods have been proposed for
      data normalization and data analysis. This paper proposes a generalized additive
      model for the analysis of gene expression data. This model consists of two sub
      models: a non-linear model and a linear model. We propose a two-step
      normalization algorithm to fit the two sub-models sequentially. The first step
      involves a non-parametric regression using lowess fits to adjust for non-linear
      systematic biases. The second step uses a linear ANOVA model to estimate the
      remaining effects including the interaction effect of genes and treatments, the
      effect of interest in a study. The proposed model is a generalization of the
      ANOVA model for microarray data analysis. We show correspondences between the
      lowess fit and the ANOVA model methods. The normalization procedure does not
      assume the majority of genes do not change their expression levels, and neither
      does it assume two channel intensities from the same spot are independent. The
      procedure can be applied to either one channel or two channel data from the
      experiments with multiple treatments or multiple nuisance factors. Two
      toxicogenomic experiment data sets and a simulated data set are used to contrast
      the proposed method with the commonly known lowess fit and ANOVA methods.

PMID- 15468753
TI  - Effect of normalization on significance testing for oligonucleotide microarrays.
AB  - MOTIVATION: Normalization techniques are used to reduce variation among gene
      expression measurements in oligonucleotide microarrays in an effort to improve
      the quality of the data and the power of significance tests for detecting
      differential expression. Of several such proposed methods, two that have commonly
      been employed include median-interquartile range normalization and quantile
      normalization. The median-IQR method applied directly to fold-changes for paired
      data also was considered. Two methods for calculating gene expression values
      include the MAS 5.0 algorithm [Affymetrix. (2002). Statistical Algorithms
      Description Document. Santa Clara, CA: Affymetrix, Inc.
      http://www.affymetrix.com/support/technical/whitepapers/sadd-whitepaper.pdf] and
      the RMA method [Irizarry, R. A., Bolstad, B. M., Collin, F., Cope, L. M., Hobbs,
      B., Speed, T. P. (2003a). Summaries of Affymetrix GeneChip probe level data.
      Nucleic Acids Res. 31(4,e15); Irizarry, R. A., Hobbs, B., Collin, F., Beazer
      Barclay, Y. D., Antonellis, K. J., Scherf, U., Speed, T. P. (2003b). Exploration,
      normalization, and summaries of high density oligonucleotide array probe-level
      data. Biostatistics 4(2):249-264; Irizarry, R. A., Gautier, L., Cope, L. (2003c).
      An R package for analysis of Affymetrix oligonucleotide arrays. In: Parmigiani,
      R. I. G., Garrett, E. S., Ziegler, S., eds. The Analysis of Gene Expression Data:
      Methods and Software. Berlin: Springer, pp. 102-119]. RESULTS: In considering
      these methods applied to a prostate cancer data set derived from paired samples
      on normal and tumor tissue, it is shown that normalization methods may lead to
      substantial inflation of the number of genes identified by paired-t significance
      tests even after adjustment for multiple testing. This is shown to be due
      primarily to an unintended effect that normalization has on the experimental
      error variance. The impact appears to be greater in the RMA method compared to
      the MAS 5.0 algorithm and for quantile normalization compared to median-IQR
      normalization.

PMID- 15468754
TI  - A graphical approach for quality control of oligonucleotide array data.
AB  - In studies of quality control of oligonucleotide array data, one objective is to
      screen out ineligible arrays. Incomparable arrays (one type of ineligible arrays)
      arise as the experimental factors are poorly controlled. Due to the high volume
      of data in gene arrays, examination of array comparability requires special
      treatments to reduce data dimension without distortion. This paper proposes a
      graphical approach to address these issues. The proposed approach uses percentile
      methods to group data, and applies the 2D image plot to display the grouped data.
      Moreover, an invariant band is employed to quantify degrees of array
      comparability. We use two publicly available oligonucleotide array datasets from
      Affymetrix GeneChip System for evaluation. The results demonstrate the utility of
      our approach to examine data quality and also as an exploratory tool to verify
      differentially expressed genes selected by vigorous statistical methods.

PMID- 15468755
TI  - Statistical approaches in the analysis of gene expression data derived from bone
      regeneration specific cDNA microarrays.
AB  - Recent advances in molecular biology (e.g., cDNA microarray technology) enables
      the simultaneous monitoring of the expression level of thousands of genes. Due to
      the massive amount of complex data generated, sophisticated statistical
      approaches are necessary in order to properly address the experimental
      investigation. In this paper, we present statistical analysis of cDNA microarray
      data derived from bone regeneration experiments. Several interesting features
      from these data distinguish it from commonly used microarray experiment (i.e.,
      separate hybridization of mRNA samples from reference and experimental tissues,
      selectively spotted cDNA sequences and 1060 systematically selected blank spots
      included in each array). Using this data set, we propose new methods for
      bioinformatic data normalization, as well as the modification and application of
      various other published methods in order to identify co-regulated gene expression
      patterns during the healing of a bone fracture. The proposed normalization
      methods perform effectively to eliminate the variations with a simple algorithm.
      Results from our cluster analysis revealed several clusters having distinct gene
      expression patterns during fracture healing. Our simulation study supports the
      reliability of the proposed methods.

PMID- 15468756
TI  - Identification of differentially expressed genes with multivariate outlier
      analysis.
AB  - DNA microarray offers a powerful and effective technology to monitor the changes
      in the gene expression levels for thousands of genes simultaneously. It is being
      widely applied to explore the quantitative alternation in gene regulation in
      response to a variety of aspects including diseases and exposure of toxicant. A
      common task in analyzing microarray data is to identify the differentially
      expressed genes under two different experimental conditions. Because of the large
      number of genes and small number of arrays, and higher signal-noise ratio in
      microarray data, many traditional approaches seem improper. In this paper, a
      multivariate mixture model is applied to model the expression level of replicated
      arrays, considering the differentially expressed genes as the outliers of the
      expression data. In order to detect the outliers of the multivariate mixture
      model, an effective and robust statistical method is first applied to microarray
      analysis. This method is based on the analysis of kurtosis coefficient (KC) of
      the projected multivariate data arising from a mixture model so as to identify
      the outliers. We utilize the multivariate KC algorithm to our microarray
      experiment with the control and toxic treatment. After the processing of data,
      the differential genes are successfully identified from 1824 genes on the UCLA
      M07 microarray chip. We also use the RT-PCR method and two robust statistical
      methods, minimum covariance determinant (MCD) and minimum volume ellipsoid (MVE),
      to verify the expression level of outlier genes identified by KC algorithm. We
      conclude that the robust multivariate tool is practical and effective for the
      detection of differentially expressed genes.

PMID- 15468757
TI  - Empirical bayes gene screening tool for time-course or dose-response microarray
      data.
AB  - An efficient method to reduce the dimensionality of microarray gene expression
      data from thousands or tens of thousands of cDNA clones down to a subset of the
      most differentially expressed cDNA clones is essential in order to simplify the
      massive amount of data generated from microarray experiments. An extension to the
      methods of Efron et al. [Efron, B., Tibshirani, R., Storey, J., Tusher, V.
      (2001). Empirical Bayes analysis of a microarray experiment. J. Am. Statist.
      Assoc. 96:1151-1160] is applied to a differential time-course experiment to
      determine a subset of cDNAs that have the largest probability of being
      differentially expressed with respect to treatment conditions across a set of
      unequally spaced time points. The proposed extension, which is advocated to be a
      screening tool, allows for inference across a continuous variable in addition to
      incorporating a more complex experimental design and allowing for multiple design
      replications. With the current data the focus is on a time-course experiment;
      however, the proposed methods can easily be implemented on a dose-response
      experiment, or any other microarray experiment that contains a continuous
      variable of interest. The proposed empirical Bayes gene-screening tool is
      compared with the Efron et al. (2001) method in addition to an adjusted model
      based t-value using a time-course data set where the toxicological effect of a
      specific mixture of chemicals is being studied.

PMID- 15468758
TI  - Statistical methods for analyzing tissue microarray data.
AB  - Tissue microarrays (TMAs) are a new high-throughput tool for the study of protein
      expression patterns in tissues and are increasingly used to evaluate the
      diagnostic and prognostic importance of biomarkers. TMA data are rather
      challenging to analyze. Covariates are highly skewed, non-normal, and may be
      highly correlated. We present statistical methods for relating TMA data to
      censored time-to-event data. We review methods for evaluating the predictive
      power of Cox regression models and show how to test whether biomarker data
      contain predictive information above and beyond standard pathology covariates. We
      use nonparametric bootstrap methods to validate model fitting indices such as the
      concordance index. We also present data mining methods for characterizing high
      risk patients with simple biomarker rules. Since researchers in the TMA community
      routinely dichotomize biomarker expression values, survival trees are a natural
      choice. We also use bump hunting (patient rule induction method), which we adapt
      to the use with survival data. The proposed methods are applied to a kidney
      cancer tissue microarray data set.

PMID- 15468759
TI  - A knowledge-based clustering algorithm driven by Gene Ontology.
AB  - We have developed an algorithm for inferring the degree of similarity between
      genes by using the graph-based structure of Gene Ontology (GO). We applied this
      knowledge-based similarity metric to a clique-finding algorithm for detecting
      sets of related genes with biological classifications. We also combined it with
      an expression-based distance metric to produce a co-cluster analysis, which
      accentuates genes with both similar expression profiles and similar biological
      characteristics and identifies gene clusters that are more stable and
      biologically meaningful. These algorithms are demonstrated in the analysis of
      MPRO cell differentiation time series experiments.

PMID- 15468760
TI  - Detection of activity centers in cellular pathways using transcript profiling.
AB  - We present a new computational method for identifying regulated pathway
      components in transcript profiling (TP) experiments by evaluating transcriptional
      activity in the context of known biological pathways. We construct a graph
      representing thousands of protein functional relationships by integrating
      knowledge from public databases and review articles. We use the notion of
      distance in a graph to define pathway neighborhoods. The pathways perturbed in an
      experiment are then identified as the subgraph induced by the genes, referred to
      as activity centers, having significant density of transcriptional activity in
      their functional neighborhoods. We illustrate the predictive power of this
      approach by performing and analyzing an experiment of TP53 overexpression in NCI
      H125 cells. The detected activity centers are in agreement with the known TP53
      activation effects and our independent experimental results. We also apply the
      method to a serum starvation experiment using HEY cells and investigate the
      predicted activity of the transcription factor MYC. Finally, we discuss
      interesting properties of the activity center approach and its possible
      applications beyond the comparison of two experiments.

PMID- 15468761
TI  - Cross-validation for linear model with unequal variances in genomic analysis.
AB  - In recent years, genomic studies are usually conducted to identify genes that may
      have an impact on clinical outcomes. The identified genes are then used to
      establish a predictive model for identifying subjects who are most likely to
      respond to the test treatment in clinical trials. This information is useful in
      early and later phases of clinical development. The United States Food and Drug
      Administration (FDA) requires that such a predictive model be validated before it
      can be used in clinical development. Shao [Shao, J. (1993). Linear model
      selection by cross-validation. J. Amer. Statist. Assoc. 88(422):486-494] proposed
      a cross-validation method for linear model with equal variances, which is found
      useful in genomic studies. In practice, however, genomic data may be obtained
      from different sources with unequal variances. As a result, Shao's method may not
      be applied directly. In this paper, we extend Shao's method for cross-validation
      of a linear model with unequal variances. Along this line, two re-sampling
      methods were proposed to account for the heterogeneity in variance. Several
      simulations were performed to evaluate the finite samples performances of the
      proposed methods. An example concerning a breast cancer research is present to
      illustrate the use of the proposed methods.

PMID- 15468762
TI  - Incorporating durability information in the comparison of proportions of patients
      with HIV suppression.
AB  - In some HIV clinical trials, the proportion of patients who achieve treatment
      success at a clinically meaningful time point (e.g., 16 or 24 weeks) and the
      subsequent durability of the treatment success after that time point are
      collected from two exclusive followup intervals. Two treatments are usually
      compared in terms of the proportion of patients achieving treatment success at
      the pre-defined time point and the subsequent durability information is ignored.
      However, combining the failure/success proportion at the pre-defined time point
      and the subsequent durability information in one test statistic could be more
      powerful if the experimental treatment is more efficacious than the control in
      that either fewer patients fail the experimental treatment at this time point or
      the responding patients have longer duration of viral suppression. In this paper,
      we propose a time-to-event type potency/durability endpoint which captures the
      information from the two exclusive followup intervals. A linear rank statistic to
      compare the two treatments in terms of this potency/durability endpoint can be
      interpreted as a weighted statistic to incorporate the potency information at a
      clinically meaningful time point (e.g., 16 or 24 weeks) and the durability
      information after that time point. The statistical hypotheses being tested by
      using this potency/durability endpoint and their clinical interpretations are
      discussed. A clinical endpoint study in anti-retroviral treatment naive patients
      is used to illustrate this method. Simulation studies show that this method is
      more powerful than comparing the success rates alone when the experimental
      treatment is also more durable in maintaining long term success.

PMID- 15468763
TI  - Three-stage sequential statistical dissolution testing rules.
AB  - The U.S. Pharmacopoeia (USP) general monograph provides a standard for
      dissolution compliance with the requirements as stated in the individual USP
      monograph for a tablet or capsule dosage form. The USP monograph sets performance
      limit on dissolution in terms of a specific percentage Q that the drug product is
      required to be dissolved at a specified time. Japan Pharmacopoeia provides
      acceptance rules different from USP. However the objective of the acceptance
      rules was not defined in terms of the inference of the whole lot by either USP,
      European Pharmacopoeia (EP) or Japan Pharmacopoeia (JP). The operating
      characteristics' curves of these rules are all shown to be sensitive to the true
      mean dissolution and do not reject a lot which has a large percentage of tablets
      that dissolve with less than the specified limit Q. This is especially true when
      the mean dissolution is close to the specification value. We proposed that the
      goal of the dissolution test sampling plan is to accept a lot at least 90% of the
      tablets dissolved more than a pre-specified amount Q at the specific time. The
      group sequential procedure derived accordingly is shown to outperform both USP
      and JP in controlling the type I error rate under normality assumption.

PMID- 15468764
TI  - Nonparametric procedures for simultaneous identification of the minimum effective
      dose in each of several groups.
AB  - This paper considers the extension of the dose finding problem in a one-way
      layout setting to the case of several groups, in which the main goal is to
      identify the minimum effective dose (MED) of each group simultaneously. We
      propose two nonparametric procedures using the respective pairwise- and Helmert
      type two-sample Mann-Whitney statistics, which are applied in a step-down testing
      scheme for identifying the MED simultaneously. The computation for the associated
      p-value of the identified MED vector is discussed. One numerical example is given
      to illustrate the proposed procedures.

PMID- 15468765
TI  - Monitoring a three-armed clinical trial with survival endpoints: Fisher's least
      significant difference approach.
AB  - Researchers have long recognized the importance of monitoring trials to determine
      whether to terminate a trial early or change a trial because of a substantial
      treatment effect. Fisher's least significant difference (LSD) procedure has been
      suggested by Proschan et al. [Proschan, M. A., Follmann, D. A., Geller, N. L.
      (1994). Monitoring multi-armed trials. Stat. Med. 13:1441-1452] to control the
      overall type I error rate for trials with three or more arms and survival
      endpoints. In this paper we propose an alternative Fisher's LSD interim
      monitoring procedure that uses the same adjusted significance levels for the
      pairwise tests as for the global test; it continues performing a global
      hypothesis test at looks subsequent to a look where a global null hypothesis was
      rejected. We also examine revised Proschan et al. approach that uses the O'Brien
      Fleming two-armed trial boundaries for pairwise tests. A simulation study shows
      that compared to the approach proposed by Proschan et al., the procedure we
      propose is more powerful and produces overall type I error rates closer to the
      nominal values when all groups are truly equivalent. For the scenarios examined,
      the overall type I error rates and power of the proposed approach are virtually
      equivalent to those of the revised Proschan et al. approach.

PMID- 15468766
TI  - Evaluating assumptions for least squares analysis using the general linear model:
      a guide for the pharmaceutical industry statistician.
AB  - A review of graphical and test based methods for evaluating assumptions
      underlying the use of least squares analysis with the general linear model is
      presented along with some discussion of robustness. Alternative analyses are
      described for situations where there is evidence that the assumptions are not
      reasonable. Evaluation of the assumptions is illustrated through the use of an
      example from a clinical trial used for US registration purposes. It is
      recommended that: (1) most assumptions required for the least squares analysis of
      data using the general linear model can be judged using residuals graphically
      without the need for formal testing, (2) it is more important to normalize data
      or to use nonparametric methods when there is heterogeneous variance between
      treatment groups, and (3) nonparametric analyses can be used to demonstrate
      robustness of results and that it is best to specify these analyses prior to
      unblinding.

PMID- 15468767
TI  - Using a serial marker to predict a repeated measures outcome in a cohort design-
      results of a simulation study.
AB  - Consider the cohort design and suppose that the outcome of primary interest is a
      continuous random variable observed repeatedly over time. Suppose that there is a
      second variable of clinical relevance which is also observed repeatedly. We are
      interested in assessing whether the "serial marker" is in some sense predictive
      of the primary outcome. We would also like to predict the trend for the primary
      outcome assuming that the clinical marker follows a profile of specific clinical
      interest. In series of earlier papers, we have addressed these issues by applying
      a bivariate repeated measures model. One regression model was prescribed to
      relate the primary outcome to important explanatory variables, while a second
      regression model was prescribed for the serial marker. In this paper, we perform
      a series of simulation studies to investigate the empirical properties of this
      approach. Bivariate repeated measures data were generated at random, and basic
      study parameters including the sample size, the number of time points, the degree
      of serial correlation within the clinical marker, and type of association between
      the serial marker and the primary outcome were varied. The ability of the
      methodology to capture the underlying relationship between the two set of
      repeated measures was assessed. The ability to predicting the primary outcome
      corresponding to a known marker profile of specific interest was examined.

PMID- 15468768
TI  - Nurses' priority must be to reduce infection risk.

PMID- 15468769
TI  - Can we rise to yet another challenge?

PMID- 15468771
TI  - We support the support groups.

PMID- 15468770
TI  - Power and women-dominated professions.

PMID- 15468772
TI  - Nurses are positive, but see room for improvement.

PMID- 15468773
TI  - Diverse services for a diverse community.

PMID- 15468774
TI  - Nurse prescribing: is it for you?

PMID- 15468775
TI  - My role is a fine balancing act.

PMID- 15468776
TI  - Meeting the needs of Muslim service users.

PMID- 15468777
TI  - Needlestick and sharps injuries: avoiding the risk in clinical practice.
AB  - What is the true incidence of needlestick and sharps injuries among health-care
      professionals in the UK and what is the real cost of such injuries? This article
      identifies the obvious and not-so-obvious risks to staff in community and
      hospital settings and examines how such risks can be minimised, drawing on
      guidance from NICE and the RCN.

PMID- 15468778
TI  - What can be done to meet the needs of older people experiencing pain?
AB  - It is a myth that older people feel pain less than younger people. They may have
      more difficulty communicating what they are experiencing, and health-care
      practitioners need to be aware of different ways of monitoring this. Obstacles
      include outdated attitudes, the underuse of opioids, and ineffective use of pain
      measurement scales.

PMID- 15468779
TI  - Do Cox-2 inhibitors have the potential to improve postoperative pain control?
AB  - With the ever-developing role of nurses in pain management and the increasing
      responsibilities for nurse prescribers, it is important for nurses to be aware of
      the current evidence base for practice in this area. This article considers some
      of the latest research surrounding Cox-2 drugs and guidance on their use.

PMID- 15468780
TI  - Make use of all resources to quit smoking.

PMID- 15468781
TI  - Surgical wound care: current views on minimising dressing-related pain.
AB  - Managing surgical wounds healing by primary intention is likely to become less
      problematic with the development of more effective advanced wound dressings;
      increasingly effective methods of medicated pain management; education; and
      advances in minimal access surgical (MAS) techniques. Future research is likely
      to focus on management of patients with surgical wounds healing by secondary
      intention. If so, management of surgical wound pain must become an integral part
      of assessment. Theatre practitioners, clinical nurses and surgical practitioners,
      working as part of the multidisciplinary team, are ideally placed to undertake
      this work and to include multimodal, holistic approaches to caring for surgical
      wounds and controlling surgical wound pain (Gould, 1999). Patient support and
      education is likely to become an increasing priority, particularly in view of the
      significant move from inpatient care to short-stay and day-case surgery.

PMID- 15468782
TI  - Making an informed choice tailored to each patient.
AB  - Nutritional supplements can be useful when the diet alone cannot provide adequate
      nutrition. They can also be used to manage certain clinical conditions. Once a
      decision is made to use them it is important to consider patient choice and
      cultural beliefs as well as which nutrients to supply.

PMID- 15468783
TI  - Developing a practical policy on working with company representatives.
AB  - Purchasing equipment and supplies for an NHS trust is a complicated business,
      with the needs of patients and staff paramount in the process and a number of
      pitfalls for the unwary. A working with company representatives' policy sets out
      clearly the procurement process so that the interests of both sides in any
      negotiations are fairly represented.

PMID- 15468784
TI  - Antimuscarinic drugs.
AB  - Antimuscarinic drugs are used to treat urinary incontinence and increase bladder
      capacity in both children and adults. Carol McLoughlin looks at when they should
      be prescribed, the adverse reactions to be aware of, and how to help patients use
      them properly as part of their treatment

PMID- 15468785
TI  - Lessons for nurses from the ombudsman's adviser.

PMID- 15468786
TI  - Effective corporate teamwork.

PMID- 15468787
TI  - Ward manager at the sharp end.

PMID- 15468788
TI  - From concept to patient--biomaterials solutions to medical problems.

PMID- 15468789
TI  - Engineering of various types of tissues in immunocompetent animals and its
      potential for clinical application.

PMID- 15468790
TI  - Tissue engineering trachea: Malaysian experience.
AB  - Management of severe tracheal anomalies remains a clinical challenge. Tissue
      engineering offers new hope in trachea reconstruction surgery. However to date no
      optimal technique achieved in the formation of human or animal trachea. The main
      problem lies on the biomaterial used and the complex city of forming trachea in
      vivo. This study was aimed at creating tissue-engineered trachea cartilage from
      easily accessible human and animal nasal septum cartilage using internal scaffold
      and biodegradable human and animal fibrin.

PMID- 15468791
TI  - Bone biology in craniofacial growth, development and ageing.

PMID- 15468792
TI  - Interaction between insulin-like growth factor-1 with other growth factors in
      serum depleted culture medium for human cartilage engineering.
AB  - The regulation roles of insulin-like growth factor-1 (IGF-1) with basic
      fibroblast growth factor (bFGF) and transforming growth factor beta 2 (TGFbeta2)
      in human nasal septum chondrocytes monolayer culture and cartilage engineering
      was investigated in this study. The role of IGF-1 with bFGF and TGFbeta2 was
      investigated by measuring chondrocyte growth kinetic and collagen genes
      expression. IGF-1 together with bFGF and TGFbeta2 promote cartilage tissue
      engineering, increase type II collagen expression and enhance the histological
      features of engineered cartilage.

PMID- 15468793
TI  - Tissue engineered human articular neocartilage using serial expanded
      chondrocytes.
AB  - Autologous cells are usually preferred in treating damaged tissue to avoid risks
      of immunological rejection and transmitting infectious diseases. Since only
      limited amount of tissue can be obtained without causing morbidity at the donor
      site, in vitro expansion of isolated cell is essential in order to acquire
      sufficient number of cells to reconstruct neocartilage. The aim of this study was
      to examine whether serial expanded chondrocytes can be use to generate
      neocartilage in vivo.

PMID- 15468794
TI  - The effects of autologous human serum on the growth of tissue engineered human
      articular cartilage.
AB  - Culture media supplemented with animal serum e.g. fetal bovine serum; FBS is
      commonly used for human culture expansion. However, for clinical application, FBS
      is restricted as its carry a risk of viral or prion transmission. Engineering
      autologous cartilage with autologous human serum supplementation is seen as a
      better solution to reduce the risk of transmitting infectious diseases and immune
      rejection during cartilage transplantation. The purpose of this study is to
      establish and compare the effects of 10% autologous human serum (AHS) and 10% FBS
      on the growth of chondrocytes and the formation of tissue engineered human
      articular cartilage.

PMID- 15468795
TI  - The significance of using pooled human serum in human articular cartilage tissue
      engineering.
AB  - Animal serum is commonly used in chondrocytes culture expansion to promote cell
      proliferation and shorten the time lag before new tissue reconstruction is
      possible. However, animal serum is not suitable for regeneration of clinical
      tissue because it has potential risk of viral and prion related disease
      transmission particularly mad cow disease and foreign protein contamination that
      can stimulate immune reaction leading to graft rejection. In this context, human
      serum as homologous supplement has a greater potential as growth promoting agents
      for human chondrocytes culture.

PMID- 15468797
TI  - Using tissue engineering techniques for osteochondral repair and regeneration.

PMID- 15468796
TI  - In vitro development of autologous tissue engineered human articular neocartilage
      for orthopaedic surgery.
AB  - Treatment of articular cartilage lesions remains a clinical challenge. The uses
      of prosthetic joint replace allograft and/or autograft transplant carry a risk of
      complications due to infection, loosening of its component, immunological
      rejection and morbidity at the donor site. There has been an increasing interest
      in the management of cartilage damages, owing to the introduction of new
      therapeutic options. Tissue engineering as a method for tissue restoration begins
      to provide a potential alternative therapy for autologous grafts
      transplantations. We aimed to evaluate how well a tissue engineered neocartilage
      implant, consist of human articular chondrocytes cultured with the presence of
      autologous serum and mixed in a fresh fibrin derived from patient, would perform
      in subcutaneous implantation in athymic mice.

PMID- 15468798
TI  - Prospects of plasma immersion ion implantation and deposition (PIlI & D) in the
      biomaterials field in Malaysia and south East Asia.
AB  - One of the emerging technologies in the area of plasma processing is plasma
      immersion ion implantation (PSII). The paper addresses the merits offered by the
      PSII technique especially in the area of biomaterial processing. Worldwide
      development status as well as the drive towards commercial applications is
      elaborated in an attempt to draw the attention to the importance of the process
      for Malaysia as well as south East Asia.

PMID- 15468799
TI  - Microstructure and properties of crystalline bioglass compositions prepared by
      polymeric route.
AB  - The standard bioglass composition GS45 as well as with excess silica GS50 or with
      the addition of 5% titanium oxide GS45+Ti5, were prepared by the polymeric route.
      The different glass components were added to the formed polymer. Firing at 700
      degrees C gave an amorphous product with microporous texture that readily
      crystallizes out at 900 degrees C. The prepared materials were highly porous with
      two modes of pore system micro-pores and macro-pores with a size ranging between
      100 microm to 0.006 microm and a porosity reaching 73%. The measured bulk density
      was between 0.36 to 1.1g/cm3. The fired material preserved the former structure
      of the polymer precursor. Biocompatibility was verified in vitro and vivo. IR of
      the specimens previously immersed in SBF revealed the formation of apatite like
      layer. While the histology sections of implants in rate femurs showed new bone
      tissue or bone trabeculae after 21 days.

PMID- 15468800
TI  - Study on the effect of Y2O3 addition to the fluorescent property of dental
      porcelain.
AB  - The appearance of dental porcelains is comparable to natural teeth. This study
      discusses the effect of Y2O3 addition to the fluorescent property of dental
      porcelains. The composition of dental porcelains contained Y2O3 as the
      fluorescent agent and base frit. The combinations of Y2O3 added consist of a
      series with 0.5, 1.0, 1.5, 2.0 and 2.5 wt% respectively, based on the total
      composition. In the extreme condition, fluorescent agents are added from 5.0 up
      to 10.0 wt%. In order to enhance the fluorescent property of dental porcelains,
      an opacifiying agent, cerium oxide (CeO2) was also added to dental porcelains
      composition. The fluorescent property was determined using Spectroline EF-1400C/F
      that emits 240 nm wavelength ultraviolet light. The microstructure was examined
      by Scanning Electron Microscope (SEM). The result shows that, the fluorescent
      properties displayed are similar to natural teeth when subjected to ultraviolet
      light. SEM micrograph was able to show the fluorescent agent dispersed in glass
      phase. Increasing additions of Y2O3 gave the fluorescent properties near to
      natural teeth.

PMID- 15468801
TI  - Mechanical and thermal properties of hydroxyaptite filled poly (methyl
      methacrylate) heat processed denture base material.
AB  - The aim of this study was to evaluate the effect of powder-to-liquid ratio on the
      glass transition temperature (Tg) and the tensile properties of denture base
      material prepared from poly (methyl methacrylate) (PMMA) and hydroxyapatite (HA)
      previously treated with 3-trimethoxysilylpropyl methacrylate (gamma-MPS).
      Specimens for mechanical testing were prepared by adding composites powder (PMMA,
      BPO and HA) to the monomer (MMA and EGDMA) followed by hand mixing as in dental
      laboratory description usage. The glass transition temperature was studied by
      using differential scanning calorimetry (DSC). It was observed that the tensile
      properties and the Tg were affected by the powder-to-liquid ratio. The mechanical
      characterization of the materials were performed by using single edge notch
      tension (SEN-T) specimens; the fracture toughness was slightly higher in
      formulation which contained HA filler compared to commercial denture base
      material.

PMID- 15468802
TI  - Comparison of linear-linear and hyperbranched-linear dental composite.
AB  - Linear polymers have been commonly used as dental composite. However the aim of
      this work is to use hyperbranched polymer in an attempt to produce dental
      composite. The reason is because the dendritic molecules have shown low viscosity
      at higher molecular weight compared to the linear counterparts. Therefore, this
      work attempts to substitute the linear polymer with as much of hyperbranched
      polymer in the dental composite that would pass the required ISO 4049:1998(E)
      "Dentistry - Resin-based filling material". Several formulations of dental
      composites were used, i.e. combinations of linear-linear and linear-hyperbranched
      polymers for comparison. Following this, physical and mechanical characterisation
      were conducted based on the ISO standards such as water sorption and water
      solubility. Other characterisation such as polymerisation shrinkage and Vickers
      hardness were also evaluated. It was found that different types of resins give
      different physical and mechanical properties. The maximum achievable
      hyperbranched polymer, which passes the required ISO standard, that can be
      incorporated in the linear polymer to form dental composite is 43% wt.

PMID- 15468803
TI  - Tissue-engineered bone applied for alveolar ridge augmentation with simultaneous
      implant.

PMID- 15468805
TI  - Tissue engineered trachea using sheep nasal septum.

PMID- 15468804
TI  - Autologous human fibrin as the biomaterial for tissue engineering.
AB  - Patient own fibrin may act as the safest, cheapest and immediate available
      biodegradable scaffold material in clinical 1 tissue engineering. This study
      investigated the feasibility of using patient own fibrin isolated from whole
      blood to construct a new human cartilage, skin and bone. Constructed in vitro
      tissues were implanted on the dorsal part of the nude mice for in vivo
      maturation. After 8 weeks of implantation, the engineered tissues were removed
      for histological analysis. Our results demonstrated autologous fibrin has great
      potential as clinical scaffold material to construct various human tissues.

PMID- 15468806
TI  - Towards engineering of a tracheal equivalent: identification of epithelial
      precursor cells, differentiation and cocultivation techniques.

PMID- 15468807
TI  - Scaffolds in bone tissue engineering.

PMID- 15468808
TI  - Quality evaluation analysis of bioengineered human skin.
AB  - Our objective is to determine the quality of tissue engineered human skin via
      immunostaining, RT-PCR and electron microscopy (SEM and TEM). Culture-expanded
      human keratinocytes and fibroblasts were used to construct bilayer tissue
      engineered skin. The in vitro skin construct was cultured for 5 days and
      implanted on the dorsum of athymic mice for 30 days. Immunostaining of the in
      vivo skin construct appeared positive for monoclonal mouse anti-human
      cytokeratin, anti-human involucrin and anti-human collagen type I. RT-PCR
      analysis revealed loss of the expression for keratin type 1, 10 and 5 and re
      expression of keratin type 14, the marker for basal keratinocytes cells in normal
      skin. SEM showed fibroblasts proliferating in the 5 days in vitro skin. TEM of
      the in vivo skin construct showed an active fibrocyte cell secreting dense
      collagen fibrils. We have successfully constructed bilayer tissue engineered
      human skin that has similar features to normal human skin.

PMID- 15468809
TI  - The use of bone marrow stem cells for bone tissue engineering.
AB  - Bone marrow stem cells (BMSC), known for its multipotency to differentiate into
      various mesenchymal cells such as chodrocyte, osteoblasts, adipocytes, etc, have
      been actively applied in tissue engineering. BMSC have been successfully isolated
      from bone marrow aspirate and bone marrow scraping from patients of various ages
      (13-56 years) with as little as 2ml to 5ml aspirate. BMSC isolated from our
      laboratory showed the presence of a heterogenous population that showed varying
      prevalence of surface antigens and the presence of telomerase activity albeit
      weak. Upon osteogenic induction, alkaline phosphatase activity and mineralization
      activity were observed.

PMID- 15468810
TI  - Strategy for generating tissue-engineered human bone construct.
AB  - The strategy used to generate tissue-engineered bone construct, in view of future
      clinical application is presented here. Osteoprogenitor cells from periosteum of
      consenting scoliosis patients were isolated. Growth factors viz TGF-B2, bFGF and
      IGF-1 were used in concert to increase cell proliferation during in vitro cell
      expansion. Porous tricalcium phosphate (TCP)-hydroxyapatite (HA) scaffold was
      used as the scaffold to form 3D bone construct. We found that the addition of
      growth factors, greatly increased cell growth by 2 to 7 fold. TCP/HA proved to be
      the ideal scaffold for cell attachment and proliferation. Hence, this model will
      be further carried out on animal trial.

PMID- 15468811
TI  - Bone marrow mesenchymal stem cells differentiation and proliferation on the
      surface of coral implant.
AB  - This study was designed to evaluate the ability of natural coral implant to
      provide an environment for marrow cells to differentiate into osteoblasts and
      function suitable for mineralized tissue formation. DNA content, alkaline
      phosptatase (ALP) activity, calcium (Ca) content and mineralized nodules, were
      measured at day 3, day 7 and day 14, in rat bone marrow stromal cells cultured
      with coral discs glass discs, while cells alone and coral disc alone were
      cultured as control. DNA content, ALP activity, Ca content measurements showed no
      difference between coral, glass and cells groups at 3 day which were higher than
      control (coral disc alone), but there were higher measurement at day 7 and 14 in
      the cell cultured on coral than on glass discs, control cells and control coral
      discs. Mineralized nodules formation (both in area and number) was more
      predominant on the coral surface than in control groups. These results showed
      that natural coral implant provided excellent and favorable situation for marrow
      cell to differentiate to osteoblasts, lead to large amount of mineralized tissue
      formation on coral surface. This in vitro result could explain the rapid bone
      bonding of coral in vivo.

PMID- 15468812
TI  - Tissue engineering techniques in tendon and ligament replacement.

PMID- 15468813
TI  - Surface properties and microporosity of polyhydroxybutyrate under scanning
      electron microscopy.
AB  - This study was designed to investigate the surface properties especially surface
      porosity of polyhydroxybutyrate (PHB) using scanning electron microscopy. PHB
      granules were sprinkled on the double-sided sticky tape attached on a SEM
      aluminium stub and sputtered with gold(10nm thickness) in a Polaron SC515 Coater,
      following which the samples were placed into the SEM specimen chamber for viewing
      and recording. Scanning electron micrographs with different magnification of PHB
      surface revealed multiple pores with different sizes.

PMID- 15468815
TI  - The effect of dialysis environment on the mechanical behaviour of hollow
      polymeric fibers.
AB  - The effect of hemodialysis on the mechanical behavior of a cellulosic Hemophane
      ME-IOH and one Polysulfone type hollow fibers was investigated. Mechanical tests
      showed that the deformation of polysulfone type of hollow fibers is entirely
      different than that of the other dialyser for the samples used and unused in
      hemodialysis. All the samples exposed to the dialysis showed decreased in
      ductility. Fracture surface studies proved that there was some alignment on the
      fracture surface. XRD and DSC experiments revealed structural changes had
      occurred.

PMID- 15468814
TI  - Poly(vinyl alcohol) : a potential matrix for glucose oxidase immobilization?
AB  - Considerable effort has been focused on the method of immobilizing glucose
      oxidase (GOD) for amperometric glucose biosensors since the technique employed
      may influence the available activity of the enzyme and thus affect the
      performance of the sensor. Narrow measuring range and low current response are
      still considered problems in this area. In this work, poly(vinyl alcohol)(PVA)
      was investigated as a potential matrix for GOD immobilization. GOD was entrapped
      in cross-linked PVA. The use of a PVA-GOD membrane as the enzymatic component of
      a glucose biosensor was found to be promising in both the magnitude of its signal
      and its relative stability over time. The optimum PVA-GOD membrane (cross-linking
      density of 0.06) was obtained through careful selection of the cross-linking
      density of the PVA matrix.

PMID- 15468816
TI  - Microbial polyhydroxyalkanoates (PHAs): an emerging biomaterial for tissue
      engineering and therapeutic applications.
AB  - Among the various biomaterials available for tissue engineering and therapeutic
      applications, microbial polyhydroxyalkanoates (PHAs) offer the most diverse range
      of thermal and mechanical properties. Of particular interest are the PHAs that
      contain 4-hydroxybutyrate such as poly(3-hydroxybutyrate-co-4-hydroxybutyrate)
      [P(3HB-co-4HB) and poly(4-hydroxybutyrate) [P(4HB)]. These polyesters can only be
      synthesized by a few types of bacteria, among which Comamonas acidovorans has the
      most efficient metabolic pathways to channel 4HB monomers. The resulting
      polyesters are bioabsorbable and are being developed as a new biomaterial for
      medical applications. By controlling the molar ratio of the monomers, it is
      possible to produce materials that are as tough and elastic as rubber.

PMID- 15468817
TI  - Characterization of collagen/chitosan films for skin regenerating scaffold.
AB  - Various proportions of chitosan/collagen films (70/30% to 95/05%) w/w were
      prepared and evaluated for its suitability as skin regenerating scaffold.
      Interactions between chitosan and collagen were studied using Fourier Transform
      Infrared spectroscopy (FTIR) and Differential Scanning Colorimetry (DSC).
      Scanning Electron Microscope (SEM) was used to investigate the morphology of the
      blend. Mechanical properties were evaluated using a Universal Testing Machine
      (UTM). The chitosan/collagen films were found to swell proportionally with time
      until it reaches equilibrium. FTIR spectroscopy indicated no chemical interaction
      between the components of the blends. DSC data indicated only one peak proving
      that these two materials are compatible at all proportions investigated. SEM
      micrographs also indicated good homogeneity between these two materials.

PMID- 15468818
TI  - Amplifying the manganese scavenging potential of Streptococcus zooepidemicus to
      reactive oxygen species during production of hyaluronic acid.
AB  - Streptococcus zooepidemicus (SZ) is an aerotolerant bacteria and its ability to
      survive under reactive oxidant challenge raises the question of the existence of
      a defense system. Thus growth, hyaluronic acid (HA) and hydrogen peroxide (H2O2)
      production by SZ in the presence of increasing concentration of Mn2+ were
      studied. The results suggested that the tested strain supported growth and HA
      production in cultures treated with 1 and 10 mM of Mn2+ regardless of H2O2
      presence in the medium. This showed that SZ have acquired elaborate defense
      mechanisms to scavenge oxygen toxicity and thus protect cells from direct and
      indirect effect of this radical. In contrast, cells treated with 25 mM Mn2+ were
      sensitive, in which, the HA production was reduced considerably. Thus showing
      that the oxygen scavenger systems of the cells may be fully saturated at this
      concentration.

PMID- 15468819
TI  - Mechanical properties of HDPE/UHMWPE blends: effect of filler loading and filler
      treatment.
AB  - Various blend ratios of high-density polyethylene (HDPE) and ultra high molecular
      weight polyethylene (UHMWPE) were prepared with the objective of determining
      their suitability as biomaterials. In the unfilled state, a blend of 50/50
      (HDPE/UHMWPE) ratio by weight was found to yield optimum properties in terms of
      processability and mechanical properties. Hydroxyapatite (HA) was compounded with
      the optimum blend ratio. The effects of HA loading, varied from 0 to 50wt% for
      both filled and unfilled blends were tested for mechanical properties. It was
      found that the inclusion of HA in the blend led to a remarkable improvement of
      mechanical properties compared to the unfilled blend. In order to improve the
      bonding between the polymer blend and the filler, the HA used was chemically
      treated with a coupling agent known as 3-(trimethoxysiyl) propyl methacrylate and
      the treated HA was mixed into the blend. The effect of mixing the blend with
      silane-treated HA also led to an overall improvement of mechanical properties.

PMID- 15468820
TI  - Preparation of naltrexone hydrochloride loaded poly (DL-lactide-co-glycolide)
      microspheres and the effect of polyvinyl alcohol (PVA) as surfactant on the
      characteristics of the microspheres.
AB  - The aim of this study was to investigate the effect of the surfactant properties
      of polyvinyl alcohol (PVA) in enhancing the yield of small size microspheres.
      Naltrexone microspheres were prepared by solvent-solvent extraction evaporation
      process. PVA of various concentrations were added into the aqueous phase prior to
      the mixing process. The addition of PVA was expected to influence the shape, size
      distribution, drug loading and drug release profile. The results indicated that
      it is desirable to increase the weight fraction of the microspheres with size
      range below 106 mm for the highest possible yield.

PMID- 15468821
TI  - Calcium phosphate bone substitutes.

PMID- 15468822
TI  - An endeavour from porous to 3D constructs bioceramics.

PMID- 15468823
TI  - Fabrication of synthetic apatites by solid-state reactions.
AB  - The paper presents a method of producing synthetic Hydroxyapatite (HA)
      Ca10(PO4)6(OH)2 and other apatites for biological use by solid-state reaction.
      The solid-state reaction involves mix-grinding dry powders of beta-tricalcium
      phosphate powder (TCP) and either calcium hydroxide (Ca(OH)2) or calcium
      carbonate (CaCO3) or combination thereof, from pure commercial chemicals or
      derived from natural limestone or from seashells, of total calcium/phosphorus
      molar ratio between 1.5 to 2.0, to particle size of less than 10 microns, and
      firing the resultant powder to temperature between 600 degrees C - 1250 degrees C
      in atmosphere or in controlled atmospheric condition. The resultant apatites
      formed were characterised using XRD, SEM-EDX and FTIR. The presented reaction
      process was found to be much simpler compared to conventional methods of
      producing synthetic apatites since it involves only dry mix-grinding of the
      reactants before firing at high temperatures based on the required levels of
      purity. It can also produce synthetic apatites with good reproducibility in a
      shorter time. Thus the presented method has a great industrial value.

PMID- 15468824
TI  - Biomimetic structures for implants and tissue engineering scaffolds.

PMID- 15468825
TI  - Lactic acid-based bioresorbable polymers: properties and traps.

PMID- 15468826
TI  - The synthesis of hydroxyapatite through the precipitation method.
AB  - Hydroxyapatite (HA) has been earmarked as suitable for implantation within the
      human of its chemical makeup to human bone. In this paper, HA powders were
      synthesized via the precipitation method where phosphoric acid (H3PO4) was
      titrated into calcium hydroxide solution [Ca(OH)2]. Two parameters such as
      temperature and stirring rate were identified as factors that influenced the
      amount and purity of HA powder. Phase identification of the synthesized powder
      was done using X-Ray Diffraction (XRD). The results show that HA phase can be
      synthesized from this titration process of Ca(OH)2 and H3PO4 with yield amount of
      HA powder around 45 - 61 grams but with less than hundred percent purity. In
      order to study the effect of heat treatment to HA crystals structure, HA powder
      was calcined at 850 degrees C for 2 hours. It's found that the degree of
      crystallinity increases after calcination because of lattice expansion when the
      materials were heated at higher temperature

PMID- 15468827
TI  - Comparison of hydroxyapatite powders derived from different resources.
AB  - There is a great demand of Hydroxyapatite (HA) material in Orthopaedics and
      Dental applications due to its similarity to human bone. However, the lack of
      availability and due to high import cost of this material in Malaysia, research
      in producing synthetic HA locally is therefore timely. The use of local resources
      as the raw materials for the production of HA is also desirable in reducing the
      overall cost of HA. In this study, two HA materials were synthesised from
      different starting precursors, i.e. commercial pure Ca(OH)2 (HAS) and Ca(OH)2
      directly from a local natural limestone deposit (HAL). Whereas a commercially
      available HA "Captal 60" (HAC) was used as reference. The synthesised powders
      obtained were fired at 1000 degrees C and at 1250 degrees C. Characterisation
      evaluations on bulk properties were carried out using XRD, SEM-EDX, ICP and FTIR.
      The results indicate that both HAS and HAL are comparable to HAC even at 1000
      degrees C. Thus, the local natural limestone can be used to form HA. However, the
      overall appearance of these materials are quite different (HAC - blue, HAS -
      greenish and HAL - light green). The reasons for this and the subsequent
      mechanical and bioactive effects of these materials are currently being
      investigated.

PMID- 15468828
TI  - HAp physical investigation--the effect of sintering temperature.
AB  - The paper presents the effect of sintering temperature on the physical properties
      of porous hydroxyapatite (HAp In this study, the HAp was prepared using polymeric
      sponge techniques with different binder concentrations. The sintering process was
      carried out in air for temperature ranging from 1200 degrees C to 1600 degrees C.
      Different physical properties namely density and porosity were observed at
      different sintering temperatures. The HAp prepared with higher PVP binder showed
      a slightly decreased in apparent density with increasing sintering temperature,
      while those HAp prepared with lower PVP showed a slightly increase in apparent
      density with increasing sintering temperature. The total porosity was found to be
      approximately constant in the whole sintering temperature range. However, closed
      porosity decreases with increasing sintering temperature for HAp prepared by
      lower binder concentration. On the other hand, the HAp prepared by higher binder
      concentrations showed increasing closed porosity with increasing sintering
      temperature. Other features such as the influence of sintering temperatures on
      grain and strut would also be presented in this paper.

PMID- 15468829
TI  - Comparative study of synthesised hyroxyapatite from pure chemicals and Malaysian
      natural limestone precursors.
AB  - Hydroxyapatite, (HA; Ca1O(PO4)6(OH)2) has been successfully applied in medical
      and dental applications for several years due to its excellent biocompatibility.
      The usage of HA in Malaysia, however, is limited due to the lack of availability.
      Therefore the aim of this work is to produce HA materials from both pure
      chemicals and from Malaysian natural limestone precursors, and to compare their
      bulk properties. However, parts of Malaysian natural limestone deposits actually
      consist of a combination of Ca(OH)2 and CaCO3. In order to utilise the limestone
      to produce HA material, the combination of these commercially pure chemicals as
      HA precursors should still work. In order to test this hypothesis, two HAs were
      produced by wet synthesis technique utilising (a) combination of Ca(OH)2 + CaCO3
      from pure commercial chemicals [WCC] and (b) a local natural limestone [WL]
      precursors. The HAs produced; WCC and WL, were compacted into discs and sintered
      at 1250 degrees C. The characterisations and evaluations conducted were XRD, SEM
      EDX, FTIR and shrinkage factor. The results indicate that WL gives slightly
      better bulk properties compared to WCC.

PMID- 15468830
TI  - Microstructure and strength of extruded porous HA ceramics.
AB  - The paper discusses the influence of sintering temperature on the microstructure
      and strength of hydroxyapatite ceramics prepared using the extrusion process. The
      average pore diameters observed were in the range of approximately 150mm to 300mm
      whereas the compaction strength was found to be around 120-160 MPa.

PMID- 15468831
TI  - Sterilisation effect study on granular hydroxyapatite (HA).
AB  - Hydroxyapatite is a calcium phosphate bioceramic that has been shown by many
      authors to be biocompatible with bioactive properties. It is widely accepted as
      the best synthetic material available for surgical use as a bone graft
      substitute. HA granules produced by AMREC-SIRIM from local materials underwent 5
      types of sterilisation techniques with different ageing periods. Samples were
      tested for chemical and phase composition and microbial contamination before and
      after being sterilised. From the microbiological tests done, none of the
      unsterilised positive control yielded a positive culture. Results from X-Ray
      diffraction studies found that all the sterilisation techniques did not
      chemically degrade or structurally change the HA granules significantly.

PMID- 15468832
TI  - The fundamentals of tissue engineering: new scaffolds.
AB  - The ability to regenerate new bone for skeletal use is a major clinical need. In
      this study, two novel porous calcium phosphate materials pure HA and biphasic
      HA/beta-Tricalcium phosphate (HA/beta -TCP) were evaluated as potential scaffolds
      for cell-seeded bone substitutes using human osteoblast-like cells (HOS) and
      primary human mesenchymal stem cells (hMSCs). A high rate of proliferation was
      observed on both scaffolds. A greater increase in alkaline phosphatase (ALP- an
      indicator of osteoblast differentiation) was observed on HA/beta -TCP compared to
      HA. This observation indicates that HA/TCP may play a role in inducing
      osteoblastic differentiation. Although further evaluation is required both
      materials show potential as innovative synthetic substitutes for tissue
      engineered scaffolds.

PMID- 15468833
TI  - Metallic materials stimulating bone formation.
AB  - Metallic materials implanted into bone defects are generally encapsulated by a
      fibrous tissue. Some metallic materials such as titanium and tantalum, however,
      have been revealed to bond to the living bone without forming the fibrous tissue,
      when they were subjected to NaOH solution and heat treatments. Thus treated
      metals form bone tissue around them even in muscle, when they take a porous form.
      This kind of osteoconductive and osteoinductive properties are attributed to
      sodium titanate or tantalate layer on their surfaces formed by the NaOH and heat
      treatments. These layers induce the deposition of bonelike apatite on the surface
      of the metals in the living body. This kind of bioactive metals are useful as
      bone substitutes even highly loaded portions, such as hip joint, spine and tooth
      root.

PMID- 15468834
TI  - Factors inducing in-stent restenosis: an in-vitro model.
AB  - In-stent restenosis is caused by the proliferation of the smooth muscle cells
      (SMCs) following a host response towards the implanted device. However, the
      precise biochemical and cellular mechanisms are still not completely understood.
      In this paper, the behaviour of SMCs has been investigated by an in vitro model
      where the cells were stimulated by platelet derived growth factor (PDGF) on
      tissue-like substrates as well as on biomaterials such as stainless steel (St)
      and diamond-like carbon (DLC)-coated St. The results demonstrated that SMCs have
      a completely different adhesion mode on St and become particularly prone to
      proliferation and pro-inflammatory cytokine secretion under PDGF stimulus. This
      would suggest that restenosis may caused by the accidental contact of the SMC
      with the St substrate under an inflammatory insult.

PMID- 15468835
TI  - "In vitro evaluation of the growth enhancing or cytotoxic effect of Sticophus
      species (Gamat) on established human fibroblast cell lines and antimicrobial
      activity.

PMID- 15468836
TI  - Cinnamtannin B1 activity on adipocytes formation.
AB  - In attempt to discover a small active compound that could promote adipogenesis,
      we investigated the ability of cinnamon (Cinnamomum zeylanicum) extracts to
      stimulate 3T3-L1 preadipocytes, In this study, we designed an experiment by
      replacing insulin with cinnamon extracts. The differentiated of 3T3-L1 adipocytes
      were monitored using oil red O staining method. Induction of adipocyte formation
      by cinnamtannin B1 or water extract gave the similar effects to insulin activity
      in adipogenesis.

PMID- 15468838
TI  - Biocompatibility test of polyhydroxybutyrate on human cell line.
AB  - The human fibroblast MRC-5 cells incubated with PHB granules (TM) added at a
      final concentration of 4 mg/ml showed a time-course pattern of survival. The
      percentages of dead cells obtained were at the rate of 3.8% after 7 days,
      respectively. When the MRC-5 cells grown in different material, using the test
      concentration of 4 mg/ml PCM, they were found to show a similar time-course
      increasing pattern of death as that obtained with PHB. However, the death was
      noted in the cells incubated for 7 days, the death rates obtained was 40.54%
      respectively.

PMID- 15468837
TI  - Cytotoxicity analysis of poly (carbonate-siloxane-urea) urethane.

PMID- 15468839
TI  - In vitro differences of hydroxyapatite from different resources in simulated body
      fluid.
AB  - Hydroxyapatite (HA; Ca10(PO4)6(OH)2), is one of the significant implant materials
      used in Orthopaedics and Dental applications. However, synthetically produced HA
      may not be stable under ionic environment, which it will unavoidably encounter
      during its applications. In this paper, the in vitro effects of three HA
      materials derived from different resources, i.e. commercial HA (HAC), synthesised
      HA from pure chemicals (HAS) and synthesised HA from kapur sireh; derived
      traditionally from natural limestone (HAK), were studied. The HA disc samples
      were prepared and immersed in simulated body fluid (SBF) for 31-day period. The
      evaluation conducted focuses on the changes of the pH and the Calcium ion (Ca
      ion) and Phosphate ion (P-ion) concentrations in the SBF solution, as well as the
      XRD and SEM data representing the reactions on the HA materials. From the XRD, it
      was found that HAK has the smallest crystallite sizes, which in turn affect the
      pH of the SBF during immersion. The Ca and P-ion concentrations generally
      decrease over time at different rates for different HA. Upon 1-day immersion in
      SBF, apatite growth was observed onto all three surfaces, which became more
      pronounced after 3-day immersion. However, the appetites formed were observed to
      be different in shapes and sizes. The reasons for the difference in the apatite
      crystals and their subsequent effects on cells are still being investigated.

PMID- 15468840
TI  - Mutagenicity of CORAGRAF and REKAGRAF in the Ames test.
AB  - Mutagenicity of CORAGRAF (natural coral) and REKAGRAF (hydroxyapatite) was tested
      in Ames test with and without an external metabolic activation system (S9). The
      test revealed no mutagenic activity of both locally produced osseous substitutes.

PMID- 15468841
TI  - Endothelialisation of poly (carbonate-siloxane-urea) urethane.

PMID- 15468842
TI  - In vitro cytotoxicity testing on valued added hydroxyapatite as bone replacement
      material.
AB  - The present in vitro evaluation indicated that the value added hydroxyapatite
      (HA) was more toxic than pure HA but the toxicity of value added HA was slight
      compared to the positive control. In this testing, the conclusion can be made
      that value added HA is less biocompatible than commercialized pure HA. This
      toxicity may be caused by both the particle size and degradation (leaching).
      Further studies should be carried out to determine whether there is particle size
      effect or leaching effect when using powder as compared to the block materials.
      The in vivo evaluation should be done to assess the reaction to this value added
      HA as compared to the pure HA.

PMID- 15468843
TI  - In vivo study of CORAGRAF: a preliminary results.
AB  - The main objective of the study was to determine the biodegradability, resorption
      and osteoconductivity potency of coral implant. Coral blocks (CORAGRAF) were
      prepared from sea coral Porites species. The blocks were implanted in the right
      mandible of rabbit model. Implants were harvested at 2 and 4 weeks intervals and
      subjected for light and scanning electron microscopy. Dense hydroxyapatite (DHA)
      was implanted in the left mandible as a control. The results of this study
      demonstrated that CORAGRAF is a good implant material that can accelerates bone
      healing and be resorbed in an acceptable time. The mechanisms of the resorption
      seemed to be the same (crumbling process), a first step where the edge of the
      coral become powdery then a second step which could be phagocytosis and
      dissolution in extracellular fluid.

PMID- 15468844
TI  - The use of freeze-dry bovine pericardium (FDBP) in diaphragmatic herniorrhaphy in
      dogs.
AB  - A study was conducted to investigate the effectiveness of freeze-dried bovine
      pericardium (FDBP) as a biomaterial in diaphragmatic herniorrhapy in dogs. Eight
      adult dogs were randomly selected and divided into two equal groups. In FDBP
      group, a diaphragmatic defect was induced and repaired with an identical size of
      FDBP. In the control group, a diaphragmatic wall was incised at three-side border
      creating a flap and sutured. Grossly, only mild intrathoracic adhesion was
      observed for most of the animals, and no herniation occured. Microscopically, the
      biomaterial incorporated into the host's tissue by ingrowth of young muscle fiber
      and massive new blood vessel formation in between the fibrous tissue.

PMID- 15468845
TI  - In vivo chromosome aberration test for hydroxyapetite in mice.
AB  - This study evaluates the cytotoxic and mutagenic effect of synthetic
      hydroxyapatite granules (source: School of Material and Mineral Resources
      Engineering, Universiti Sains Malaysia) in the bone marrow cells of mice. Mice
      are exposed to synthetic hydroxyapatite granules, the bone marrow cells are
      collected and observed for chromosome aberrations. No chromosome aberrations were
      noticed in the animals exposed to distilled water (negative control) and to the
      test substance, synthetic hydroxyapatite granules (treatment) groups. Chromosome
      aberrations were observed in the animals exposed to Mitomycin C (positive control
      group). There was no indication of cytotoxicity due to synthetic hydroxyapatite
      granules in the animals as revealed by the mitotic index. Hence, synthetic
      hydroxyapatite granules are considered non-mutagenic under the prevailing test
      conditions.

PMID- 15468846
TI  - Glycerol preserved bovine pericardium for abdominal wall reconstruction:
      experimental study in rat model.
AB  - The aim of this study was to evaluate bovine pericardium surgical patch in rat
      model. Bovine pericardial sacs collected from local abattoir were cleaned,
      disinfected and cut into pieces of 3 by 2.5cm and preserved in 99.5% glycerol.
      Full thickness abdominal wall defects of 3 by 2.5 cm were created in 30 adult
      male Sprague Dawley rats and repaired with glycerol preserved pieces. The rats
      were serially sacrificed in a group of six rats at 1,3,6,9 and 18 weeks post
      surgical intervals for morphological and tensometeric study. Macroscopically, no
      mortality or postoperative surgical complications was encountered except slight
      adhesions between implanted grafts and some visceral organs in 10% of the rats.
      Microscopically no calcification or foreign body giant cell formation was found
      in the explanted grafts. The implanted grafts were replaced gradually with
      recipient tissue, which made mainly of dense collagenous bundles. The healing
      strength between the implanted grafts and the recipient abdominal wall was
      gradually increased with time. The results of this study showed that glycerol
      preserved bovine pericardium act as scaffold for transformation into living
      tissue without clinical complications such as that associated with prostheses.

PMID- 15468847
TI  - An in vivo study of a locally-manufactured hydroxyapatite-based material as bone
      replacement material.
AB  - Defects were created in the mandible of a rabbit model whereby the right side was
      implanted with hydroxyapatite (HA) while the left side was left empty to act as
      control. Both the implant and control sites were evaluated clinically and
      histologically at 4,12,20,22 weeks. Decalcified sections were studied under
      confocal laser scanning microscope. No reactive cells were evident
      microscopically in all sections. There was bone ingrowth as early as 4 weeks when
      viewed by the topographic method. Enhancement of osteoconduction was evident by
      the presence of abundant capillaries, perivascular tissue and osteoprogenitor
      cells of the host. At 22 weeks, the implanted defect showed mature bone formation
      filling almost the whole field. This study demonstrated that the dense HA
      exhibits excellent biocompatibility as noted by the complete absence of reactive
      cells. It also promotes osteoconduction.

PMID- 15468848
TI  - A comparative study of osseointegration phenomenon in coated and non-coated NiTi
      implants in a rabbit model.
AB  - There was a significant increased in Absolute Contact Length measurements of
      endosteal bone growth along the Nickel-Titanium (NiTi) implant coated with the
      natural coral powder and Hydroxyapatite (HA) compared to the non-calcium coated
      implants. This study demonstrated that coated implants seemed to show earlier and
      higher osseointergration phenomena compared to non coated ones. Furthermore,
      there was significantly greater bone-to-implant contact at the apical 1/3rd of
      the coated implants.

PMID- 15468849
TI  - Histological evaluation of the early bone response to hydroxyapatite (HA)
      implanted in rabbit tibia.
AB  - This study is to qualitatively evaluate a locally produced hydroxyapatite (HA),
      made by AMREC-SIRIM in an experimental animal bone defect using New Zealand White
      (NZW) rabbits. HA cylindrical blocks measuring 2.5 mm (D) x 1.0 mm (H) were
      implanted in the rabbits' left tibia. The tibias were harvested within one to
      three weeks post-implantation. The implantion site was cut into thin
      undecalcified sections of about 30 microm to 60 microm and stained with Toluidine
      Blue and Goldner's Masson Trichrome. Microscopic examinations using standard
      light microscopy of these slides were performed.

PMID- 15468850
TI  - The effect of chicken, pigeon, and turkey demineralized bone matrix (DBM)
      implanted in ulnar defects fixed with the intramedullary-external skeletal
      fixator (IM-ESF) tie-in in pigeons (Columba livia): histological evaluations.
AB  - Avian demineralized bone matrix (ADBM) powder prepared from chicken, pigeon, and
      turkey sources induced bone formation via endochondral and intramembranous
      processes, as in mammalian studies. There were no significant differences in
      percentage of new bone, percentage of cartilage, surface-forming osteoblast area,
      or osteoclast count between gaps treated with chicken, pigeon, and turkey DBM.
      However, there was a significantly (p<0.05) higher percentage of inflammatory
      area in gaps treated with chicken DBM than in gaps treated with pigeon DBM.

PMID- 15468851
TI  - Microscopic evaluation of the natural coral (Porites spp.) post-implantation in
      sheep femur.
AB  - The study was carried out with the aim to evaluate natural coral (Porites spp.)
      implanted in sheep femur microscopically. Twelve adult, male sheep were used in
      this study. The defect area was implanted with coral and monitored for up to 12
      weeks. The sheep were euthanased at 2,4,8, and 12 weeks post-implantation.
      Microscopically, natural coral implanted into bone tissue have shown gradual
      resorption and progressively replaced by new bone. At 12 weeks post-implantation,
      the implanted site was almost completely surrounded by mature bone. The results
      showed that natural coral was found to be a biodegradable and osteo-conductive
      biomaterial, which acted as a scaffold for a direct osteoblastic apposition.

PMID- 15468852
TI  - A "healthy apatite" for bone repair.
AB  - Bone is unique in its ability to adapt structure to functional requirements, but
      as is all too obvious in an ever-ageing population it is susceptible to a number
      of degenerative diseases. Therefore there is an increasing need for materials for
      bone replacement. Clearly, the ideal material with which to replace bone, would
      be bone itself, but the major problem now facing us is that there is an
      insufficient supply of the natural bone to satisfy the clinical requirements.
      Hence, there is a need for the development of chemically synthesised bone graft
      substitutes

PMID- 15468853
TI  - Design and fabrication of scaffolds for anatomic bone reconstruction.

PMID- 15468854
TI  - Biomaterials research in Malaysia--development in facilities and expertise for in
      vivo evaluation.

PMID- 15468855
TI  - Synthesis and characterization of poly(p-phenylene vinylene).
AB  - Poly (p-phenylene vinylene) (PPV) was synthesized from p-xylylene
      bis(tetrahydrothiophenium chloride) using the Wessling route and characterized by
      Fourier Transform Infra-Red (FTIR) and UV-visible (UV-VIS) spectroscopic
      techniques. The significance of thermal treatment along with evolution of
      precursor polymer to polymer PPV was also studied through these spectroscopic
      techniques. Thermally Stimulated Current (TSC) measurements indicated the
      presence of crystallization, sulphonium group which occurred through the
      evolution from precursor polymer to polymer PPV during thermal treatment.

PMID- 15468856
TI  - Antibacterial activity of chitosan under physiological conditions.

PMID- 15468857
TI  - Radiation and temperature effects on conductivity properties of PVA-KOH-PC
      composite.
AB  - The aim of this work was to study radiation and the effects of temperature on
      conductivity properties of polyvinyl alcohol (PVA)-based potassium hydroxide
      (KOH) and propylene carbonate (PC), where the ionic conduction preferentially
      occurs in the amorphous phase by free radicals ions through gamma-irradiation.
      Alkaline composite polymer electrolyte (ACPE) consisting of PVA, KOH and PC of
      different concentration ratios were prepared by solvent-casting technique. The
      ACPE were irradiated with different doses from 5 kGy up to 200 kGy. The
      conductivity properties of the electrolyte films were measured at different
      frequencies in the range 20 Hz to 1 MHz using LCR meter. The results showed that
      the conductivity properties were dependent on the radiation dose, temperature and
      the concentration of the polymer blends.

PMID- 15468858
TI  - Synthesis and characterization of poly (methyl methacrylate)/SiO2 hybrid
      membranes: effect of solvents on thermal properties.
AB  - Hybrid organic-inorganic membranes were fabricated using sol-gel technique using
      PMMA and TEOS with 80/20 (w/w) ratio at various solvents. The thin membrane films
      were then characterized using DSC and TGA. From DSC analysis, the Tg value of the
      PMMA moieties in hybrids membranes was in the order H-15-Toluene < Pure PMMA < H
      15-THF < H-15-DMF. Furthermore, from TGA analysis it was found that the hybrid
      membranes have higher thermal stability compared to pure PMMA, and the type of
      solvents used play an important role in their degradation behavior.

PMID- 15468859
TI  - Study on changing the coefficient of thermal expansion (CTE) of dental porcelain.
AB  - Raising the thermal expansion coefficient (CTE) of dental porcelains is important
      to match the CTE of the ceramic material with the higher CTE of the metal inlay
      in dental restorations. The higher thermal expansion of the leucite phase
      increases the overall thermal expansion coefficient of the dental porcelain.
      Potassium nitrate (KNO3) additions in controlled percentages to the base dental
      porcelain formulation help in the formation of a leucite phase. The percentage
      added was 5,10 and 20 weight percent of leucite, respectively, to the total base
      frit composition. The change in CTE values was then investigated using a Linseis
      Dilatometer. A 20wt% KNO3 addition resulted in a CTE of 9.0 microm/m-K compared
      to the 7.7 microm/m-K CTE of the base composition. The microstructures observed
      under the scanning electron microscope (SEM) show a multiphase material with the
      leucite phases dispersed within a glassy matrix. The results suggest that higher
      CTEs in the dental porcelain are possible by increasing the KNO3- additions
      within the limits tested.

PMID- 15468860
TI  - Tensile strength and water absorption of alumina filled poly (methyl
      methacrylate) denture base material.
AB  - The aim of this study was to evaluate the tensile properties and water absorption
      of denture base material prepared from high molecular weight poly methyl
      methacrylate (PMMA) and alumina (Al2O3) as particulate filler. Specimens for
      mechanical testing were prepared by adding composite powder to the monomer
      followed by hand mixing as in dental laboratory procedure. The tensile strength
      of the prepared denture base material was slightly higher than commercial denture
      base material, while the water absorption was almost the same for all formulation
      of denture base materials.

PMID- 15468864
TI  - Plasma-sprayed coating of hydroxyapatite on metal implants--a review.
AB  - Metal implants such as titanium, stainless steel and Co-Cr-Mo are used for load
      bearing purposes such as hip joint prostheses, fixing plates and dental root
      implants. For practical application, plasma-sprayed coatings of hydroxyapatite
      (HA) on metal implants are applied to promote early formation of strong bonds
      between metal implant and living bone. Plasma spray coating involves heating of
      HA material to a semi-molten or molten state and then propels its to a metal
      substrate. The plasma flame temperature is in the range of 6,000 degrees C to
      16,000 degrees C but the surface temperature of the substrate rarely exceeds 150
      degrees C. The HA materials are feed into the spray gun in the form of powders.
      Furthermore, this paper will discuss the processes of plasma-sprayed coating of
      HA on various types of metal implants.

PMID- 15468861
TI  - Effect of powder to liquid ratio on tensile strength and glass transition
      temperature of alumina filled poly methyl methacrylate (PMMA) denture base
      material.
AB  - The aim of this study was to evaluate the mechanical properties and glass
      transition temperature (Tg) of a denture base material prepared from high
      molecular weight poly methyl methacrylate (PMMA) and alumina (Al2O3). The glass
      transition temperature was studied by using differential scanning calorimetry
      (DSC). The effect of powder-to-liquid ratio was investigated. The result showed
      that the tensile properties and the Tg were slightly effected by the powder-to
      liquid ratio. The ratio of 2.2:1 by weight of powder to liquid was found to be
      the best ratio for mixing the material to give the best result in this
      formulation.

PMID- 15468863
TI  - Comparative study between dense and porous hydroxyapatite using light and
      scanning electron microscopy.
AB  - This in vivo study revealed that porous hydroxyapatite (PHA) and dense
      hydroxyapatite (DHA) are good implant materials that can accelerate bone healing
      and resorbed in acceptable time. But there were differences in the mechanism of
      the resorption of DHA and PHA due to variability in the physical properties and
      osteogenicity.

PMID- 15468862
TI  - Locally produced bovine bone sponge as a haemostatic agent.
AB  - The aim of this study was to evaluate the morphological and biological properties
      of a locally produced "Bovine Bone Sponge" for use in dentistry. Bovine bone
      sponge was prepared from local calf bone. Endotoxin level and surface properties
      were investigated. The pore size and water uptake ability were measured and
      results were compared with the commercial haemostatic agent. The material was
      tested for its haemostatic property and its inhibition of alveolar bone
      resorption in a sheep model following dental extraction. Results revealed a
      significant difference in haemostatic effect, and a shorter bleeding time and a
      lower rate of alveolar bone resorption in bovine bone sponge compare to a
      commercial haemostatic agent.

PMID- 15468865
TI  - Hydroxapatite and tricalcium phosphate prepared by precipitation method.
AB  - A mixture with different compositions of HA and TCP were synthesize in this work
      by precipitation method using Ca(NO3)2 4H2 and (NH4)2HPO4 as the starting
      materials. A mixture with HA and TCP phases in different ratios were produced.
      The powders were sintered from 1000 degrees C to 1250 degrees C. The phase
      compositions of the mixtures were then studied via XRD. This work shows that the
      pH value determines the different phase compositions of the HA-TCP mixture.
      Chemical analyses were carried out by FTIR. The microstructure was observed under
      SEM.

PMID- 15468866
TI  - The influence of sintering temperature on the porosity and strength of porous
      hydroxyapatite ceramics.
AB  - The present paper reports on the influence of sintering temperature on the
      porosity and strength of porous hydroxyapatite (HA). HA powder was first prepared
      by the sol-gel precipitation method using calcium hydroxide and ortho-phosporic
      acid. The fine HA powder, measuring <50 microm was then mixed into a slurry with
      the addition of binder agent, being a mixture of sago and PVA. A small amount of
      sodium dodecyl sulphate was also used as a foaming agent. Porous HA samples were
      then prepared via slip casting technique. The surface morphology of the sintered
      samples was observed under scanning electron microscopy at 20 kV and the
      compositions were determined via SEM-EDX. A universal testing machine was used to
      determine the compaction strength of the sintered samples.

PMID- 15468867
TI  - Synthesis of nanosized hydroxyapatite powders.
AB  - Hydroxyapatite powder was mechanochemically synthesized from calcium
      pyrophosphate (Ca2P2O7) and calcium carbonate (CaCO3) using a solid-state
      reaction. The two powders were mixed in distilled water, milled for 8 hours,
      dried and calcined at 1100 degrees C for 1 hour. The phase(s) formed was analyzed
      by x-ray diffraction (XRD). It was found that hydroxyapatite was not the only one
      formed. This result will be used as the starting point to produce a single-phase
      hydroxyapatite in terms of excess hydroxyl group in a mechanochemical reaction.

PMID- 15468869
TI  - Predicting graded young modulus values of Ti alloys modified by ion implantation.
AB  - There has been, and is still, concern about the high elastic modulus of Ti alloys
      compared to bone. Any reduction in the Young's modulus value of the implant is
      expected to enhance stress redistribution to the adjacent bone tissues, minimize
      stress shielding and eventually prolong device lifetime. Dynamic Monte Carlo
      simulation is used to predict the gradual reduction in Young's modulus values
      between the bulk of Ti alloys and the modified surface layers due to Ca ion
      implantation. The simulation can be used as a screening step when applying new
      alloys and/or coatings.

PMID- 15468870
TI  - Gene expressions screening of human cell line exposed to locally produced
      biomaterial.
AB  - In Malaysia, the field of genomics in toxicology is still in infancy. The purpose
      of this study is to focus on the use of toxicogenomics for determination of gene
      expressions changes in cultured human fibroblast cells treated with
      genotoxicology free biomaterial (using Ames test), a locally produced
      hyroxyapatite. Dose and time response is similar to Ames test with time interval
      up to 21 days. mRNA is extracted, followed with RT-PCR and polyacrilamide gel
      electrophoresis. Changes of the gene expressions compared to the non-treated
      fibroblast mRNA would suggest some gene interactions in the molecule level
      associated with the exposure of the fibroblast cell line to the biomaterials.
      Further analysis (cloning & sequencing) shall be carried out to investigate the
      genes involved as simple changes might not signified toxicity.

PMID- 15468868
TI  - Synthesis of nano-sized hydroxyapatite.
AB  - In this work, nanometer HA crystals have been synthesized via wet chemical
      precipitation and characterized. This research studies how key synthesis
      parameters affect the size and phase purity of the produced HA. Characterization
      work was carried out using X-ray powder diffraction method and scanning electron
      microscopy for phase identification and particle sizing, respectively.

PMID- 15468871
TI  - Chromosome aberration test for hydroxyapatite in sheep.
AB  - The present study is aimed at finding the mutagenicity and cytotoxicity of dense
      form of synthetic hydroxyapatite (Source: School of Materials and Mineral
      Resources Engineering, Universiti Sains Malaysia) in the blood of sheep. The
      biomaterial was implanted in the tibia of Malin, an indigenous sheep breed of
      Malaysia. Blood was collected from the sheep before implantation of the
      biomaterial, cultured and a karyological study was made. Six weeks after
      implantation, blood was collected from the same animal, cultured and screened for
      chromosome aberrations. The mitotic indices and karyological analysis indicated
      that the implantation of synthetic hydroxyapatite (dense form) did not produce
      any cytotoxicity or chromosome aberrations in the blood of sheep.

PMID- 15468872
TI  - DNA damage evaluation of hydroxyapatite on fibroblast cell L929 using the single
      cell gel electrophoresis assay.
AB  - Hydroxyapatite is the main component of the bone which is a potential biomaterial
      substance that can be applied in orthopaedics. In this study, the
      biocompatibility of this biomaterial was assessed using an in vitro technique.
      The cytotoxicity and genotoxicity effect of HA2 and HA3 against L929 fibroblast
      cell was evaluated using the MTT Assay and Alkaline Comet Assay respectively.
      Both HA2 and HA3 compound showed low cytotoxicity effect as determined using MTT
      Assay. Cells viability following 72 hours incubation at maximum concentration of
      both HA2 and HA3 (200 mg/ml) were 75.3 +/- 8.8% and 86.7 +/- 13.1% respectively.
      However, the cytotoxicity effect of ZnSO4.7H2O as a positive control showed an
      IC50 values of 46 mg/ml (160 microM). On the other hand, both HA2 and HA3
      compound showed a slight genotoxicity effect as determined using the Alkaline
      Comet Assay following incubation at the concentration 200 mg/ml for 72 hours.
      This assay has been widely used in genetic toxicology to detect DNA strand breaks
      and alkali-labile site. The percentage of the cells with DNA damage for both
      substance was 27.7 +/- 1.3% and 15.6 +/- 1.0% for HA2 and HA3 respectively.
      Incubation of the cells for 24 hours with 38 microg/ml (IC25) of positive control
      showed an increase in percentage of cells with DNA damage (67.5 +/- 0.7%). In
      conclusion, our study indicated that both hydroxyapatite compounds showed a good
      biocompatibility in fibroblast cells.

PMID- 15468873
TI  - Effect of differences in physical and chemical properties of chitosan on
      endothelial cell adhesion and growth.

PMID- 15468876
TI  - Gross, radiology and ultrasonographic evaluation of coral post-implantation in
      sheep femur.
AB  - The study was carried out to evaluate macroscopically the ability of coral to
      repair a large size bone defect. A total 12 adult, male sheep were used in the
      study. The large bone defect (2.5cm x 0.5cm x 0.5cm) was created surgically on
      the left proximal femur and replaced by a block of coral (Porites sp.).
      Radiographs were obtained immediately after surgery and at 2, 4, 8 and 12 weeks
      post-implantation. Ultrasonographic examinations were carried out every 2 weeks
      after implantation up to 12 weeks using ultrasound machine (TOSHIBA Capasee II)
      connected with 7MHz frequency transducer. The sheep were euthanased at 2, 4, 8,
      and 12 weeks post-implantation and the bone examined grossly. Both
      ultrasonographs and radiographs taken at 8 and 12 weeks showed that the implants
      had been resorbed and left the space that much reduced in size. There was no sign
      of implant rejection observed in all animals. The results showed that processed
      coral has potential to become bone substitute for reconstructive bone surgery.

PMID- 15468877
TI  - Failure analysis of stainless steel femur fixation plate.
AB  - Failure analysis was performed to investigate the failure of the femur fixation
      plate which was previously fixed on the femur of a girl. Radiography,
      metallography, fractography and mechanical testing were conducted in this study.
      The results show that the failure was due to the formation of notches on the
      femur plate. These notches act as stress raisers from where the cracks start to
      propagate. Finally fracture occurred on the femur plate and subsequently, the
      plate failed.

PMID- 15468874
TI  - In vitro cytotoxicity evaluation of biomaterials on human osteoblast cells CRL
      1543; hydroxyapatite, natural coral and polyhydroxybutarate.
AB  - The aim of this study was to evaluate the in vitro cytotoxicity of biomaterials;
      Hydroxyapatite (HA), Natural coral (NC) and Polyhydroxybutarate (PHB). Three
      different materials used in this study; HA (Ca10(PO4)6(OH)2), NC (CaCO3) and PHB
      (Polymer) were locally produced by the groups of researcher from Universiti Sains
      Malaysia. The materials were separately extracted in the complete culture medium
      (100mg/ml) for 72h and introduced to the osteoblast cells CRL-1543. The viability
      of osteoblast CRL-1543 cultivated with these extraction materials after 72h
      incubation period was compared to negative control with neutral red assay by
      using spectrophotometer at 540nm. The results showed the non-cytotoxicity of the
      materials. After 72h of incubation period, HA showed 123% viable cells, NC was
      99.43% and PHB was 176.75%. In this study, cytotoxicity test dealt mainly with
      the substances that leached out from the biomaterial. The results obtained showed
      that the materials were not toxic and also promoted cells growth in the sense of
      biofunctionality.

PMID- 15468879
TI  - Collagen fibers an important entity in skin tissues remodeling.
AB  - Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM)
      evaluation were carried out in the in vivo skin construct using fibrin as
      biomaterial. To investigate its progressive remodeling, nude mice were grafted
      and the Extracellular Matrix (ECM) components were studied at four and eight
      weeks post-grafting. It was discovered that by 4 weeks of remodeling the skin
      construct acquired its native structure.

PMID- 15468875
TI  - Cell death induced by hydroxyapatite on L929 fibroblast cells.
AB  - Biomaterials intended for end-use application as bone-graft substitutes have to
      undergo safety evaluation. In this study, we investigated the in vitro cytotoxic
      effects especially to determine the mode of death of two hydroxyapatite compounds
      (HA2, HA3) which were synthesized locally. The methods used for cytotoxicity was
      the standard MTT assay whereas AO/PI staining was performed to determine the mode
      of cell death in HA treated L929 fibroblasts. Our results demonstrated that both
      HA2 and HA3 were not significantly cytotoxic as more than 75% cells after 72
      hours treatment were viable. Furthermore, we found that the major mode of cell
      death in HA treated cells was apoptosis. In conclusion, our results demonstrated
      that these hydroxyapatite compounds are not cytotoxic where the mode of death was
      primarily via apoptosis.

PMID- 15468878
TI  - The effects of age on monolayer culture of human keratinocytes for future use in
      skin engineering.
AB  - Skin is the largest organ in human system and plays a vital role as a barrier
      against environment and pathogens. Skin regeneration is important in tissue
      engineering especially in cases of chronic wounds. With the tissue engineering
      technology, these skins equivalent have been use clinically to repair burns and
      wounds. Consented redundant skin samples were obtained from patients aged 9 to 65
      years old. Skin samples were digested with dispase, thus separating the epidermis
      and the dermis layer. The epidermis layer was trypsinized and cultured in DKSFM
      in 6-well plate at 37 degrees C and 5% CO2. Once confluent, the culture were
      trypsinized and the cells were pooled. Cells were counted using haemacytometer.
      Doubling time and viability were calculated and analysed. From the result, we
      conclude that doubling time and viability of in vitro keratinocytes cultured in
      DKSFM media is not age dependant.

PMID- 15468880
TI  - Comparison of chitosan scaffold and chitosan-collagen scaffold: a preliminary
      study.
AB  - Chitosan has similar structure to glycosaminoglycans in the tissue, thus may be a
      good candidates as tissue engineering scaffold. However, to improve their cell
      attachment ability, we try to incorporate this natural polymer with collagen by
      combining it via cross-linking process. In this preliminary study we evaluate the
      cell attachment ability of chitosan-collagen scaffold versus chitosan scaffold
      alone. Chitosan and collagen were dissolved in 1% acetic acid and then were
      frozen for 24 hours before the lyophilizing process. Human skin fibroblasts were
      seeded into both scaffold and were cultured in F12: DMEM (1:1). Metabolic
      activity assay were used to evaluate cell attachment ability of scaffold for a
      period of 1, 3, 7 and 14 days. Scanning electron micrographs shows good cell
      morphology on chitosan-collagen hybrid scaffold. In conclusion, the incorporation
      of collagen to chitosan will enhance its cell attachment ability and will be a
      potential scaffold in tissue engineering.

PMID- 15468881
TI  - Phenotypic expression of collagen type II and collagen type I gene in monolayer
      culture of human auricular chondrocytes.
AB  - Cartilage is regularly needed for reconstructive surgery. Basic research in
      tissue engineering is necessary to develop its full potential. We presented here
      the expression profile of type II collagen gene and type I collagen gene in human
      auricular monolayer culture expansion. Cultured chondrocytes documented a
      reduction in the expression level of collagen type II gene whilst collagen type I
      gene was gradually expressed through all the passages. This study demonstrated
      that human auricular chondrocytes lose its phenotypic expression during monolayer
      culture expansion. Further studies are required to enhance cartilage specific
      gene expression, collagen type II throughout the in vitro culture.

PMID- 15468882
TI  - Gene expression characteristic in human auricular cartilage tissue engineering.
AB  - This study was to assess collagen type II and collagen type I gene expression in
      tissue-engineered human auricular: cartilage formed via tissue engineering
      technique. Large-scale culture expansions were transformed into 3D in vitro
      construct and were implanted subcutaneously on the dorsal of athymic mice. After
      8 weeks, explanted construct was processed in the same manner of native cartilage
      to facilitate cells for gene expression analysis. Isolated cells from in vivo
      construct demonstrated expression of type II collagen gene comparable to native
      cartilage. This study verified that tissue-engineered auricular cartilage
      expressed cartilage specific gene, collagen type II after in vivo maturation.

PMID- 15468883
TI  - Formation of tissue-engineered human auricular cartilage via tissue engineering
      technique for future use in ear surgery.
AB  - To date there is no optimal approach to reconstruct an external ear. However,
      advances in tissue engineering technologies have indicated that in vitro
      autologous elastic cartilage might be of great importance in the future treatment
      of these patients. The aim of this study was to observe monolayer expansion of
      auricular cartilage and to evaluate engineered cartilage using standard
      histochemical study.

PMID- 15468884
TI  - Human serum provided additional values in growth factors supplemented medium for
      human chondrocytes monolayer expansion and engineered cartilage construction.
AB  - We have previously formulated an optimized human chondrocytes growth medium based
      on 2% fetal bovine serum supplementation. For clinical usage, the animal serum
      must be replaced by patient own serum. We investigated the effects of human serum
      concentration for human nasal septum chondrocytes monolayer culture and cartilage
      reconstruction. Human serum demonstrated a dose dependent manner in promoting
      chondrocytes growth and cartilage engineering.

PMID- 15468885
TI  - Age and gender effect on the growth of bone marrow stromal cells in vitro.
AB  - Bone marrow harvested by aspiration contains connective tissue progenitor cells
      which can be selectively isolated and induced to express bone phenotype in vitro.
      The osteoblastic progenitor can be estimated by counting the number of cells
      attach using the haemacytometer. This study was undertaken to test the hypothesis
      that human aging is associated with a significant change on the number of
      osteoblastic progenitors in the bone marrow. Bone marrow aspirates were harvested
      from 38 patients, 14 men (age 11-70) and 24 women (age 10-70) and cultured in
      F12: DMEM (1:1). In total 15 bone marrow samples have been isolated from patients
      above 40 years old (men/women) of age. Fourteen (93.3%) of this samples failed to
      proliferate. Only one (6.7%) bone marrow sample from a male patient, aged 59
      years old was successfully cultured. Seventy percent (16/23) of the samples from
      patient below than 40 years old were successfully cultured. However, our
      observation on the survival rate for cells of different gender from patient below
      40 years old does not indicate any significant difference. From this study, we
      conclude that the growth of bone marrow stromal cells possibly for bone
      engineering is better from bone marrow aspirates of younger patient.

PMID- 15468886
TI  - Evaluation of suitable biodegradable scaffolds for engineered bone tissue.
AB  - Tricalcium phosphate/hydroxyapatite (TCP/HA), hydroxyapatite (HA), chitosan and
      calcium sulphate (CaSO4) were studied and evaluated for possible bone tissue
      engineered construct acting as good support for osteogenic cells to proliferate,
      differentiate, and eventually spread and integrate into the scaffold. Surface
      morphology visualized by SEM showed that scaffold materials with additional
      fibrin had more cell densities attached than those without, depicting that the
      presence of fibrin and collagen fibers were truly a favourite choice of cells to
      attach. In comparison of various biomaterials used incorporated with fibrin,
      TCP/HA had the most cluster of cells attached.

PMID- 15468887
TI  - Tissue-engineered bone via seeding bone marrow stem cell derived osteoblasts into
      coral: a rat model.
AB  - In the present study, natural coral of porites species was used as scaffold
      combined with in vitro expanded bone marrow stem cell derived osteoblasts (BMSC
      DO), to develop a tissue-engineered bone graft in a rat model. Coral was molded
      into the shape of rat mandible seeded with 5x10(6) /ml BMSC-DO subsequently
      implanted subcutaneously in the back of 5 week Sprague dawely rats for 3 months.
      Coral alone was implanted as a control. The implants were harvest and processed
      for gross inspection and histological observations. The results showed that newly
      bone grafts were successfully formed coral seeded with cells group showed smooth
      highly vascularized like bone tissue. Histological sections revealed mature bone
      formation and lots of blood vessel, the bone formation occurred in the manner
      resemble intramembraneous bone formation. This study demonstrates that coral can
      be use as a suitable scaffold material for delivering bone marrow mesenchymal
      stem cells in tissue engineering.

PMID- 15468888
TI  - Coral--polyhydroxybutrate composite scaffold for tissue engineering:
      prefabrication properties.
AB  - In this study the surface properties of two particulate coral and
      polyhydroxybutrate (PHB) were studied in order to characterize them prior to use
      in composite production. Coral powder and PHB particle were evaluated using
      scanning electron microscopy and confocal laser scanning microscopy, to measure
      surface porosity and pores size. The results showed that coral powder has
      multiple pleomorphic micropores cross each others give appearance of micro
      interconnectivity. Some pore reached to 18 microm with an average porosity of
      70%. PHB revealed multiple different size pores extended to the depth, with an
      average some times reach 25 microm and porosity 45%. These findings demonstrate
      that both coral and PHB have excellent pores size and porosity that facilitate
      bone in growth, vascular invasion and bone development. We believe that
      incorporation of coral powder into PHB will make an excellent composite scaffold
      for tissue engineering.

PMID- 15468889
TI  - Collagen as potential cell scaffolds for tissue engineering.
AB  - Selections of collagen available commercially were tested for their
      biocompatibility as scaffold to promote cell growth in vitro via simple collagen
      fast test and cultivation of mammalian cells on the selected type of collagen. It
      was found that collagen type C9791 promotes the highest degree of aggregation as
      well as cells growth. This preliminary study also indicated potential use of
      collagen as scaffold in engineered tissue.

PMID- 15468890
TI  - Percutaneous intramedullary supracondylar nailing for fractures of distal femur.
AB  - A prospective study of 25 patients with supracondylar and intercondylar fracture
      of the femur was carried out from January 1999 to June 2003 at SSG Hospital,
      Baroda, India. Twenty-eight percent fractures were open and 72% were closed.
      Twelve pecent of the fractures had intraarticular extension. AO classification
      was used to classify the fractures. Eighty-four percent of the fractures were due
      to high velocity trauma. All the cases were operated by percutaneous
      supracondylar nailing. No postoperative complication related to fracture
      treatment was seen. Average follow up was 20.1 months (range 6-40 months).
      Average age of the patients was 31.5 years. Average time of union was 3.1 months
      (range 2-4 months). Average knee range of motion was 117 degrees. Even in open
      injuries, 85.7% had more than 110 infinity range of motion. All patients could
      return to their pre-injury lifestyle. Rating scale developed by Hospital for
      Special Surgery was used to quantify the results. Eighty-four percent showed
      excellent, 8% showed good and 8% showed fair results. Percutaneous supracondylar
      nailing is thus, an excellent method of treating fractures of distal femur.

PMID- 15468891
TI  - The effect of neem (Azadirachta indica) extract and dietary selenium on
      distribution of selenium in hepatocarcinogenesis induced rat.
AB  - Neem, Azadirachta indica, is a plant from the family Meliaceae, known as "Pokok
      Semambu" in Malay community. It has been extensively used in India as traditional
      Ayurvedic and folklore minedicine for the treatment of various diseases. This
      study aimed to determine the distribution of selenium in the liver of rats during
      hepatocarcinogenesis when neem aqueous extract and dietary selenium was
      supplemented.

PMID- 15468892
TI  - Synthesis of precursor of anti-inflammatory agents by using highly reactive zinc.
AB  - Highly reactive zinc metal was prepared by electrolysis of a N,N
      dimethylformamide (DMF) solution containing naphthalene and a supporting
      electrolyte in a one-compartment cell fitted with a platinum cathode and a zinc
      anode. This highly reactive electrogenerated zinc (EGZn/Naph) was used for
      transformation of ethyl 2-bromoacrylate into the corresponding organozinc
      compound, which can not be achieved by the use of usual zinc metals. Reaction of
      the organozinc compounds thus prepared with various aryl halides in the presence
      of 5 mol% of palladium catalyst gave the corresponding cross-coupling products in
      high yields. These cross-coupling reactions were successfully applied to a
      synthesis of the precursor of anti-inflammatory agents such as ibuprofen,
      naproxen, cicloprofen and suprofen.

PMID- 15468893
TI  - Dose response characteristics of polymethacrylic acid gel (PMAAG) for a
      polymerization-based dosimeter using NMR.
AB  - The radiation-response characteristics of polymetharylic acid gel dosimeter
      prepared with different concentrations of monomer and cross-linker is described
      in these studies. The dosimeters were prepared under the hypoxic condition in a
      glove box and were then irradiated with gamma-rays produced by Co-60 radionuclide
      that was generated at 1.25MeV energy. The irradiation took place at different
      doses ranged from 0Gy to 19Gy. Due to the radiation activities, chain-reaction
      polymerisation processes had taken place in the formation of polymethacrylic acid
      (PMAA) gel, which cause the dose response mechanism increased in the NMR
      relaxation rates of protons. It has been observed that for higher concentration
      of monomer and cross-linker, the polymerization rate was increased.

PMID- 15468894
TI  - Distribution of molar mass and branching index of natural rubber from Hevea
      brasiliensis trees of different age by size exclusion chromatography coupled with
      online viscometry.
AB  - Natural rubber from hevea brasiliensis trees (Thailand, RRIM 600 clone) of
      different age (8, 20, and 35 years) were characterized by size exclusion
      chromatography coupled with online viscometry according to their distribution of
      molar mass and branching index at a temperature of 70 degrees C using cyclohexane
      as solvent. Washing with an aqueous solution of sodium dodecylsulfate and
      subsequent saponification purified the natural rubber samples. With this
      procedure physical branching points caused by phospholipids, proteins and
      hydrophobic terminal units, mainly fatty acids, of the natural rubber (cis-1,4
      polyisoprene) molecule, could be removed leading to completely soluble polymer
      samples. All samples investigated possess a very broad (10 to 50,000 kg/mol) and
      distinct bimodal molar mass distribution. With increasing age the peak area in
      the low molar mass region decreases favoring the peak area in the high molar mass
      region. By plotting the branching index as a function of the both, the molar mass
      and the age of the trees.

PMID- 15468895
TI  - Biosorption of phenol from aqueous solution by biosolids.
AB  - Studies on the removal of phenol from aqueous solutions by adsorption on sewage
      treatment plant biosolids (BS) as low-cost adsorbent were carried out with an aim
      to obtain information on treating phenol-containing wastewater from different
      industries. A series of experiments were undertaken in a batch adsorption
      technique to access the effect of the process variables i.e. initial phenol
      concentration, contact time, initial pH and adsorbent dose. The results showed
      that the adsorption capacity of BS in aqueous solution increased with the
      decrease in initial concentration and pH, and increase in contact time and dose
      of adsorbent. The experimental results were fitted by Langmuir and Freundlich
      isotherms to describe the biosorption processes.

PMID- 15468896
TI  - Structural elucidation of peloton lysis using epi-fluorescence dyes.

PMID- 15468897
TI  - [In cases of familial ovarian cancer, always consider the risk of breast cancer].
AB  - A family history of ovarian cancer without breast cancer can be a pitfall in
      interpreting the high breast cancer risks. A family with high breast and ovarian
      cancer risks due to a BRCA1 or BRCA2 mutation, can present itself with ovarian
      cancer only. In three women, 43, 50 and 61 years of age, there was a family
      history of ovarian cancer. In the youngest woman breast carcinoma was diagnosed
      and she was referred for genetic counseling and DNA mutation analysis. She was
      identified with a pathogenic mutation in BRCA1 and decided for regular breast
      examination and prophylactic adnectomy. The 50-year-old woman presented with
      ovarian cancer and was found to have a BRCA1 mutation. She received surgery and
      chemotherapy for her ovarian cancer and regular examination of the breasts. The
      third woman at risk could be reassured, since she did not carry the BRCA1
      mutation that was found in her affected sister. Because the patients and their
      family members can benefit from regular surveillance and prophylactic surgery, it
      is of great importance to identify the high breast cancer risks as well as the
      high ovarian cancer risks in these families.

PMID- 15468898
TI  - [The disquieting consequences of granting patents on human genes for healthcare
      and scientific research in The Netherlands].
AB  - The granting of a patent by the European Patent Office to Myriad Genetics on the
      sequence of the BRCA-1 gene in 2001 prompted the Dutch Minister of Healthcare and
      the Minister of Education, Culture and Science to ask for advice. The Royal
      Netherlands Academy of Arts and Science (KNAW) prepared a report in 2003
      entitled: 'The consequences of granting patents on human genes for scientific
      research in The Netherlands'. Another recommendation (by Van de Bunt) entitled:
      'A code of gene patenting' was also published in 2003. The KNAW report
      recommends, among others: a redefinition of the 'research exemption' and renewed
      discussion on a 'grace period'. The Van de Bunt report concludes, among other
      things, that some holders of gene patents cause unwanted side effects, but that
      the patent system itself provides sufficient possibilities to prevent these side
      effects. In a comment on both reports, the Dutch Ministry of Healthcare
      concluded: 'There is no reason to change the current patent system'. One should
      be more critical, however, and favour the possibility of a 'diagnostic exemption'
      in which DNA-diagnostics would be excluded from patenting.

PMID- 15468899
TI  - [Practical guidelines for the prevention of chronic symptoms after a whiplash
      injury, based on published evidence].
AB  - Recently, systematic reviews and evidence-based guidelines on whiplash have
      appeared, from which preventive recommendations can be derived. Fear of moving,
      catastrophic thoughts and avoidance of activity seem to play an important role in
      the transition from acute to chronic symptoms. Early reassurance and the advice
      to remain active can prevent the development of chronic symptoms following
      whiplash. In the acute and subacute phase, if there is still no recovery despite
      information designed to reduce anxiety, referral to a physiotherapist for active
      exercise therapy and management is indicated. In the chronic phase, depending on
      which factors play a role in the given patient, referral to active exercise
      therapy or a multi-disciplinary training programme may be considered.

PMID- 15468900
TI  - [Completing a course of drug therapy is necessary to combat the infection, not to
      discourage emergence of resistance].
AB  - For the treatment of infections, it is usually recommended to 'complete the
      course' so as to avoid the development of resistance. There is little evidence,
      however, for the exact duration of treatment. Only a few pathogenic
      microorganisms are able to develop resistance during exposure to effective
      antibiotic concentrations. Commensal flora are often destroyed during treatment,
      which can lead to colonisation with resistant mutants. Excretion of antibiotics
      in the urine will expose microorganisms in the environment, leading to
      resistance. Longer exposure will lead to more resistance. Only the time needed to
      clear up the infection should determine the duration of treatment and not the
      arbitrary length of an antibiotic dosage schedule.

PMID- 15468901
TI  - [Diagnostic image (204). A man with abdominal pain and fever].
AB  - In a 53-year-old man with acute sigmoid diverticulitis abdominal CT revealed
      septic thrombophlebitis with gas configurations in the inferior mesenteric vein.

PMID- 15468902
TI  - [The surgical treatment of nonpalpable breast carcinoma in a university teaching
      hospital and a general teaching hospital by residents-in-training and surgeons;
      comparable results].
AB  - OBJECTIVE: To compare the results of the surgical treatment of nonpalpable breast
      cancer between two teaching hospitals in The Netherlands; the University Medical
      Centre Utrecht (UMCU) and the Rijnstate Hospital, Arnhem (RHA). DESIGN:
      Retrospective. METHOD: A total of 240 patients from the UMCU (n = 126) and the
      RHA (n = 114) diagnosed with a malignancy at stereotactic histological needle
      biopsy from 1 February 1997-31 May 2002 were included. The average age of the
      patients at the RHA was 61.3 and at the UMCU 58.0 years. The total number of
      procedures was recorded, as well as the type of operation and whether the first
      surgeon was a resident-in-training or registered as a surgeon. RESULTS: Of the
      240 patients, biopsy results showed that 163 had invasive carcinoma (IC) and 77
      had a ductal carcinoma in situ (DCIS). In 74% of cases one operation was
      sufficient (79% in the RHA versus 69% in the UMCU; p = 0.08). In the RHA fewer
      operations per patient were carried out before radical resection was attained
      (1.25 versus 1.4; p = 0.02). IC was more often treated by breast conserving
      surgery in the RHA than in the UMCU (74% versus 55%; p = 0.01). The intention to
      treat DCIS by breast conserving surgery was more often seen in the UMCU than in
      the RHA (90% versus 69%; p = 0.02). Of all operations analysed in the RHA 48%
      were performed by a resident-in-training as first surgeon versus 87% in the UMCU
      (p < 0.001). In those patients whose first operation was carried out by a
      resident-in-training, the percentages of 'radical resections' were equal: 78% in
      the RHA and 77% in the UMCU. CONCLUSION: Outcomes of surgical treatment were
      comparable in both types of teaching hospital. Good results were achieved in
      nonpalpable breast cancer surgery that was carried out by residents-in-training.

PMID- 15468903
TI  - [Pleural mesothelioma in women is associated with environmental exposure to
      asbestos].
AB  - OBJECTIVE: To determine whether local environmental exposure to asbestos in the
      community of Hof van Twente, The Netherlands (which houses a large asbestos
      cement facility and has a serious environmental asbestos pollution problem), is
      accompanied by an increased mortality due to pleural mesothelioma among women.
      DESIGN: A descriptive, ecologic-epidemiological study. METHOD: Twenty-nine women
      with a verified diagnosis of pleural mesothelioma were selected from 810 requests
      for compensation submitted to a specialised lawyers' office in the period 1990
      2002. Information on asbestos exposure from occupational, household,
      environmental or unknown sources was obtained. The place of residence was
      compared to information on sources of asbestos in the immediate environment
      derived from the settlement 'Asbestos removal in the environment'. The expected
      number of cases of pleural mesothelioma among women was estimated on the basis of
      the observed mortality in The Netherlands in the period 1996-2002. A standardised
      mortality ratio (SMR) was calculated as the ratio of observed cases divided by
      the number of expected cases of pleural mesothelioma x 100. RESULTS: In total, 5
      cases of pleural mesothelioma were identified among women without occupational or
      household exposure to asbestos. The age at diagnosis varied from 38 to 81 years.
      Each case was exposed to asbestos in the direct vicinity of the residence through
      walking and cycling over local roads metalled with asbestos cement scrap
      material. The expected number of cases of mortality due to pleural mesothelioma
      in the town of Hof van Twente for the period 1996-2002 was about 0.46. The SMR
      was 1090 (95% CI: 465-2551), indicating a 10-fold increase in risk. CONCLUSION:
      The increased mortality of pleural mesothelioma was most probably due to
      environmental exposure to asbestos. This finding agrees with comparable studies
      in other countries.

PMID- 15468904
TI  - [Three patients with hereditary multiple exostoses and malignant degeneration of
      an osteochondroma located in the pelvis].
AB  - In three male patients with hereditary multiple exostoses (HME), aged 50, 29 and
      31 years, peripheral low-grade chondrosarcoma in the pelvic region led to
      swelling or pain. In the first patient, curative resection was not feasible
      because of the size and extension of the tumour. However, rapid tumour growth and
      unbearable pain necessitated a debulking procedure 16 months later.
      Histopathologic examination revealed a highly malignant dedifferentiated
      chondrosarcoma. The patient died two years after initial presentation as a result
      of local tumour growth. In the second patient, treatment consisted of wide
      resection of the tumour. Five years after the surgery the patient was free of
      disease. The third patient was initially treated by intralesional resection,
      followed by partial hemipelvectomy because of residual tumour. Thirteen months
      later, a local recurrence occurred that was treated by wide excision. Four years
      after the partial hemipelvectomy the patient was both pain-free and disease-free.
      Patients with HME are at increased risk for malignant degeneration of pelvic
      osteochondroma to chondrosarcoma. Periodic control of patients with pelvic
      osteochondromas is advised, preferably once every two years.

PMID- 15468905
TI  - [The treatment with methylphenidate of demoralisation, apathy and hypoactive
      delirium in patients with somatic illness].
AB  - In 3 patients, 2 women aged 21 and 65 and a man aged 60, admitted for the
      treatment of B-cell lymphoma, trauma caused by a traffic accident and Kahler's
      disease respectively, hypoactive delirium, apathy of unknown origin and
      depressive disorder or adjustment disorder with depressive mood
      ('demoralisation') were seen and caused somatic recovery to be compromised. The
      consulting psychiatrist prescribed methylphenidate with good results. They formed
      part of a group of 34 patients who were given methylphenidate on these
      indications over a period of 12 months. These indications are not among the
      accepted indications for this drug. In the literature, the beneficial use of
      psychostimulants in somatic illness has been described almost exclusively in
      palliative care and case reports of other somatically-ill patients with a poor
      prognosis. No reports were found on the effects of methylphenidate used for
      treatment of patients with hypoactive delirium nor were guidelines for its use in
      somatically-ill patients with a good prognosis. A randomised clinical trial to
      substantiate these reported findings is warranted.

PMID- 15468906
TI  - [What is the anticoagulant guideline after ablation due to atrial fibrillation?].

PMID- 15468907
TI  - [Obstructive jaundice after surgery of the biliary tract: a benign stricture or
      not?].

PMID- 15468908
TI  - [Important prognostic significance of a sentinel-node biopsy in patients with
      malignant melanoma].

PMID- 15468909
TI  - [No spectacular rise in claims for medical damages in the Netherlands: 1993-'01
      compared to 1980-'90].

PMID- 15468910
TI  - [The practice guideline 'Atrial fibrillation' from the Dutch College of General
      Practitioners; a response from the perspective of general practice].

PMID- 15468911
TI  - Neither the tumor necrosis factor alpha-308 A/G polymorphism nor the alpha2
      macroglobulin polymorphism was associated with late-onset Alzheimer's disease in
      the Chinese population.
AB  - Late-onset Alzheimer's disease (LOAD) is the most common cause of dementia in the
      elderly. It is a complex and genetically heterogeneous disorder. Epidemiological
      studies demonstrated that nonsteroidal anti-inflammatory drugs could prevent or
      delay the onset of LOAD suggesting inflammation may be involved in AD. Tumor
      necrosis factor (TNF) is a potent immunomodulator and it might increase the
      production of amyloid beta(Abeta), which makes it an appropriate AD candidate
      gene. Alpha2 macroglobulin (A2M) is a serum protease inhibitor and a major low
      density lipoprotein receptor-related protein (LRP) ligand. It can bind Abeta and
      mediate its clearance and degradation, suggesting it might be another AD
      candidate gene. In the present study, we analyzed the a 5 bp Ins/Del polymorphism
      of A2M gene (A2M-2), TNF alpha-308 A/G polymorphism and apolipoprotein E (APOE)
      polymorphisms of 67 sporadic late-onset AD patients and 142 normal elderly
      controls in the Chinese population. Our data showed that the APOE epsilon4 allele
      frequency in AD was significantly higher than that in the normal controls (chi2 =
      11.66, P < 0.01) neither the frequencies of genotypes nor alleles of the TNF
      alpha-308 A/G and A2M polymorphisms were significantly different between AD and
      controls,suggesting the two polymorphisms were not risk factors to LOAD in
      Chinese.

PMID- 15468912
TI  - [Molecular cloning and identification and biological activity of GIF-interacting
      protein(s)].
AB  - In order to examine the elusive functional mechanism of GIF (Neuronal growth
      inhibitory factor, GIF) and elucidate the possible relationship between GIF and
      Alzheimer's disease, we constructed bait1 plasmid (pHyblex-GIF) by cloning GIF
      cDNA directly in frame with plasmid pHyblex, and used the yeast two-hybrid system
      to screen Alzheimer's disease human brain cDNA library and found the GIF
      interacting proteins. The final results from coimmunoprecipitation and western
      blotting experiments confirmed that interacting proteins specifically binds to
      GIF. After sequencing the nucleotide of the putative positive plasmids and
      searching for homologues, we found that one of these is the part of human nuclear
      dUTPase protein sequence. Then the dUTPase genes are cloned into pGEX-4T-1, the
      fusion expression vector of GST,and highly expressed in E. coli BL21. The
      proteins dUTPase and GIF were purified and obtained by affinity chromatography,
      thrombin digestion and gel filtration on Sephacryl S100. It demonstrated that the
      proteins dUTPase and GIF had the growth inhibitory activity on co-cultured neuron
      in vitro. The inhibitory curve was very similar to the GIF. It's possible that
      dUTPase is one of the proteins interacting with GIF in Alzheimer's disease human
      brain extracts.

PMID- 15468913
TI  - [Comparing gene density and GC content between two large genomic blocks at short
      arm of chromosome 3].
AB  - The present paper is to investigate gene distribution at different genomic region
      with different local GC content. With shout-gun technology, we sequencing two
      sequences at 3p25.1 and 3p26.1, at genome size 328 kb and 753 kb respectively.
      The 328 kb sequence,with an average GC content as high as 47.57%, has high gene
      density (13.7 gene/100 kb). However, another sequence at 3p26.1 only includes one
      exon and one intron of large gene GRM7 and the coding sequence size is 11 520 bp
      only taking a small part (1.31%) of the whole genome region. High percentage
      distribution of GC-rich repeats of SINEs explain high GC genomic region at 3p25.1
      and high concentration of AT-rich repeats of LINEs at 3p26.1 lead to low GC
      content of the region. Our results suggest isochore structure is the result of
      coevolution between gene and genome.

PMID- 15468915
TI  - Comparative allozyme analysis of two geographic populations of Pararcyptera
      microptera meridionalis in China.
AB  - The genetic structure of the two populations of Pararcyptera microptera
      meridionalis (Ikonn.) from Hebei and Liaoning in China was analyzed with
      horizontal starch gel electrophoresis. Among 15 loci of 11 enzymes identified in
      zymograms, Adk-1, Fbp-1, Mdh-2 and G3pd-1 showed low variability with few
      alleles. Higher allelic polymorphisms were observed at Fbp-2, Mdh-1 and Me-1. The
      two populations demonstrated high percentage of polymorphic loci (93.3% and
      100.0%) but low observable overall heterozygosity (0.061 and 0.086), that could
      be attributed to heterozygote deficiencies, which led to the genotype frequency
      deviating from Hardy-Weinberg expectations. It is reasoned that the strong
      movement capability of the insect makes the individuals likely to be exposed to
      drastically varied environments, which tends to maintain dynamic equilibrium of
      genetic polymorphisms. The F-statistics between the two populations was
      comparatively smaller ( F(st) = 0.084), but larger when compared with those in
      migratory locusts like Locusta migratoria manilensis. Nei's genetic identity (I)
      and Roger's genetic distance (D) also showed close genetic relationship of the
      two populations by their high genetic identity (I = 0.904) and small genetic
      distance (D = 0.256). However,considerably qualitative and quantitative
      differences were noted at loci Acp-1 (F(st) = 0.462) and Pgi-1 (F(st) = 0.182).

PMID- 15468914
TI  - [Molecular cloning for an alternatively splicing cDNA of human PKNOX1 gene and
      it's expression analysis].
AB  - Down's syndrome (DS) is the most common chromosomal abnormality in live born
      infants. The cloning and characterization of genes on HC21 are necessary steps
      for the understanding of the molecular basis of Down's syndrome. To search for
      new Down's syndrome related genes, we have used bioinformatics analysis and rapid
      amplification of cDNA ends to identify an alternatively splicing cDNA of human
      PKNOX1 in Down's syndrome critical region on the long arm of human chromosome 21.
      The alternatively splicing full length cDNA of human PKNOX1, named PKNOX1B, is 2
      793 bp in length and encodes a 405 amino acid protein. Bioinformatical studies
      show PKNOX1B gene spans over 58 kb on chromosome 21q22.3 and contains 11 exons
      and 10 introns. The predicted molecule weight of PKNOX1B is 44.628 kDa, and the
      deduced iso-electric point is 6.28. Compared with PKNOX1 gene, PKNOX1B is 30 aa
      shorter at the C terminus than PKNOX1 owing to alternative splice between (10th
      exon and 11th exon) last two exons. PKNOX1B posses a same homeobox-domain as
      PKNOX1, so the isoform of PKNOX1 may be involved in the genetic control of
      development like other members of homeobox-containing gene family. RT-PCR results
      showed that PKNOX1B is expressed in all examined tissues except in marrow tissue.
      By Northern blot, PKNOX1 has three transcripts in adult testis, one about 5 kb,
      second about 2.9 kb, and third about 2 kb. The two larger transcript is expressed
      in all examined tissues, but the smallest transcript is only expressed actively
      in adult testis, so that it may play potential roles in spermatogenesis.

PMID- 15468916
TI  - [Triploid crucain carp-allotetraploid hybrids (male) x goldfish( hermaphrodite)].
AB  - A new type of triploid crucian carp was generated by mating the males of the
      allotetraploid hybrids of red crucian carp (Carassius auratus red var.) (female)
      x common carp (Cyprinus carpio L.) (male), with the females the goldfish(
      Carassius auratus red var.) which was red in color and possessed the biforked
      tails. The biological characteristics of one-year old triploid crucian carp
      including the number and karotype of chromosome, gonadosomatic indices and
      gonadal structures, appearance and growth rate were investigated. The results
      indicated that the triploid crucian carp possessed 150 chromosomes with the
      karyotype: 33m + 51sm + 33st + 33t. In the breeding season, the gonadosomatic
      indices (GSI) of the ovaries and testes in the triplpoid crcuian carp were,
      respectively, lower than those in the diploid red crucian carp, and the tissue
      sections showed that both the ovaries and the testes in the triploid cruican carp
      were not able to produce the mature ova and sperm, respectively, indicating that
      they were sterile during one year. The triploid crucian carp was gray in color
      and had a single fork tail. They had other morphological traits intermediate to
      the paternal allotetraploid hybrids and the maternal goldfish, for example, one
      pair of very short and not readily visible barbells, the formula of lateral line
      scales: 31-6/7, 18 dorsal fin spines, and 0.5 in ratio of the width to the length
      of the body which was evidently higher than that (0.41) in another kind of
      triploid crucian carp called Xiangyun crucian carp, generated by crossing the
      males of the allotetraploid hybrids with the females of the Japanese crucain carp
      (Carassius auratus cuvieri T. et S.). Following 8-month culture, the triploid
      crucian carp averagely reached 350 gram in which the maximum individual weighed
      550 gram. Among one- year old triploid crucian carp, the females grew faster than
      the males. Compared with Xiangyun crucian carp, the new type of triploid crucian
      carp not only presented some advantages the Xiangyun crucian carp had, for
      example, fast growth rate and potential sterility, but also got some new good
      performances like the high ratio of the width to the length of the body and the
      sweet flesh, suggesting they will be very potential in the commercial interest.

PMID- 15468917
TI  - [The shh promoter of zebrafish directs the expression of GFP in notochord].
AB  - In vitro experiment showed that HNF3beta was the direct regulator of sonic
      hedgehog (shh) promoter. To investigate the activity of zebrafish shh promoter in
      vivo, we constructed the expression vector pShh-EGFP with ligating a 538 bp
      zebrafish shh promoter,which contained two HNF3beta binding sites, to EGFP. The
      pShh-EGFP DNA was microinjected into one-cell stage embryos of the zebrafish and
      the embryos were observed for GFP expression with fluorescent microscopy. GFP
      expression started during gastrulation in the axial hypoblast layer. During
      segmentation, GFP was detected in the notochord but not in the foor plate. Our
      experiment demonstrated that the 538 bp shh promoter containing two HNF3beta
      binding sites is able to confer the notochord-expressing activity.

PMID- 15468918
TI  - [Analysis of genetic relationship among Chinese native chicken breeds using
      microsatellites marker].
AB  - The allele frequencies, heterozygosity (H), mean heterozygosity, polymorphism
      information content (PIC) and genetic relationships were studied in Luyuan
      chicken, Gushi chicken, Tibetan chicken, Baier chicken, Xianju chicken, Chahua
      chicken, Dagu chicken,Beijing Fatty chicken, Langshan chicken, Henan Game
      chicken,Taihe Silkies chicken and Xiaoshan chicken using seven microsatellite DNA
      markers. The results showed that there were differences among allele fequencies
      of seven microsatellite loci in 12 Chinese native chicken breeds. Among the 12
      Chinese native chicken breeds, mean heterozygosity of Luyuan chicken was the
      highest (0.5929), and that of Chahua chicken was the lowest (0.3514). There were
      similar results in PIC. By fuzzy cluster analysis was found that the genetic
      relationship between Taihe Silkies chicken and Henan Game chicken was the
      nearest, and that between Gushi chicken and the other chicken breeds was the most
      distant. The 12 Chinese native chicken breeds were divided into three group by
      fuzzy cluster analysis. The first group included Taihe Silkies chicken, Henan
      Game chicken, Langshan chicken, Xiaoshan chicken, Dagu chicken, Beijing Fatty
      chicken and Luyuan chicken, the second group included Chahua chicken, Tibetan
      chicken, Xianju chicken and Baier chicken, and the third group included Gushi
      chicken.

PMID- 15468919
TI  - [HPRT gene knock-out from rat fetal neural stem cells].
AB  - The 3.0 kb 5' arm (long arm, LA) of rat HPRT gene knock-out vector was cut by Sal
      I from rat HPRT gene genomic bacterial artificial chromosome (BAC) , and the 1.7
      kb 3' arm (short arm, SA) was proliferated by PCR. Neo', 5' arm, 3' arm were
      sequentially cloned into pBS vector's relative restriction enzyme sites. For
      acquirement of tk gene, the 5' arm -Neo' -3' arm fragment inserted into pKO
      vector to construct pKO-HPRT. The pKO-HPRT was linearized by Not I, extracted by
      ethidium bromide, butanol and phenol/chloroform, and dialyzed by 0.025
      microlmol/L Millipore. At the same time, rat neural stem cells cultured from
      E14.5-16.5 rat fetal brain. Passage 2 rFNSCs was tranfected by linearized pKO
      HPRT with Fugene-6t transfection reagents. After 80 microg/ml G418 and 0.2
      micromol/L ganciclovir selection, the survived cells was cultured in suspension
      to form neural spheres. The spheres can be picked up under the microscopy, and
      proliferated in 96- ,48- and 24-well plates sequentially. When the cell number
      reached 4 x 10(3)/well, half cells was lysed by lysis buffer to extract DNA, the
      other half was kept on growing to freeze and extract RNA. The knock-out cell
      colonies first detected by PCR, then confirmed by Southern blot and RT-PCR. All
      the results show that we have knocked out HPRT gene in three rat fetal neural
      stem cell colonies from 32 colonies.

PMID- 15468920
TI  - [Study on mitochondrial DNA genetic diversity of some cattle breeds in China].
AB  - The complete mitochondrial D-loop sequences, 910 bp in length, in 22 individuals
      from 8 cattle breeds in China were analyzed. The results showed that A% + T% was
      about 61.65%. Comparisons of these 22 sequences revealed 66 polymorphic sites,
      and 5 types of mutation, transition, transversion, insertion, deletion and
      coexistence site of transition and transversion were observed,with the percentage
      of 81.82%, 6.06%, 7.57%, 3.03%, 1.52%, respectively. In reference to complete
      mtDNA D-loop of the European cattle as a control, eight Chinese cattle breeds
      were classified into 3 groups according to the average percentage of D-loop
      nucleotide variations. The lowest average percentage of mtDNA D-loop nucleotide
      variation was in Xizhen cattle, Mongolian cattle, Holstein, Qinchuan cattle with
      0.37%, 0.44%, 0.52%, 0.66%, the mediate in Nanyang cattle and Jiaxian cattle with
      1.91%, 2.02% and the highest in Jinnan cattle and Yueyang cattle with 4.47%,
      4.73%, respectively. The average sequence divergence estimated from D-loop region
      within breeds and among breeds in China varied from 0.55% - 5.39% and 1.21% -
      6.59%, respectively. Comparisons of these 22 sequences revealed 19 mitochondrial
      haplotypes, the percentage of haplotype was 86.36%, showing that abundant
      mitochondrial genetic diversity exists in Chinese cattle. The molecular
      phylogenetic tree of mtDNA D-loop of 8 Chinese cattle breeds was constructed by
      Neighbor-Joining method. The NJ tree indicated that these mtDNA sequences fell
      into 3 distinct haplotype groups, it also suggested in molecular level that there
      were probably 3 maternal origins, of which the main origins of Chinese cattle
      were from Bos taurus and Bos indicus.

PMID- 15468921
TI  - Characterization of the genetic basis for yield and its component traits of rice
      revealed by doubled haploid population.
AB  - Main-effect QTL, epistatic effects and their interactions with environment are
      important genetic components of quantitative traits. In this study, we analyzed
      the QTLs, epistatic effects and QTL by environment interactions (QE) underlying
      nine traits of yield and yield-component, using a doubled-haploid (DH) population
      consisted of 190 lines from the cross between an indica parent Zhenshan 97 and a
      japonica parent WYJ 2, and tested in two-year replicated field trials. A genetic
      linkage map with 179 SSR (simple sequence repeat) marker loci was constructed. A
      mixed linear model approach was applied to detect QTLs, digenic interactions and
      QEs for the nine traits. In total, 57 QTLs of main effects, 41 digenic
      interactions, eight QEs and seven interactions of epistasis by environment were
      detected. Each of the main-effect QTLs individually explained 1.3 % to 25.8% of
      the phenotypic variations. And they collectively explained 11.5% to 66.8% of the
      phenotypic variations for these traits. Most of the traits (except seed setting)
      had the QTLs simultaneously detected in two years. Many of the traits shared same
      QTLs with each other, which is consistent with their significant phenotypic
      correlations. The pleiotropism or tight linkage of QTLs for different traits
      might be the important genetic base for trait correlations. The environmental
      influences on the stability of the trait performance were also discussed.

PMID- 15468922
TI  - [Genetic diversity analysis of maize recurrent selection populations by SSR
      marker].
AB  - Two cycles of mass (MS) and half-sib (HS) recurrent selection and one cycle of
      marker-assisted selection (MAS) for yield were carried out in two synthetic maize
      populations DC0 and XFC0, respectively. The genetic diversity of five maize (Zea
      mays L.) populations, including basic population DC0 and its developed
      populations HSC2, MSC2, and basic population XFC0 and its developed populations
      XFC1, were evaluated by 49 SSR primers, which are averagely distributed on 10
      maize chromosomes. On the 49 SSR loci, a total of 185 alleles had been detected
      in these populations. At each locus, 1 to 7 alleles could be detected, with an
      average of 3.8. The proportion of polymorphic sites differed in the five maize
      populations, which were 90.3%, 85.9%, 84.9%, 85.9%, 80.5% for DC0, HSC2, MSC2,
      XFC0 and XFC1, respectively. Genotypes can be showed by the difference of the
      alleles detected on the 49 SSR loci. There were totally 430, 392, 377, 399 and
      395 genotypes for DC0, HSC2, MSC2, XFC0 and XFC1, respectively. The mean gene
      heterozygosity calculated from the 185 alleles were 0.660, 0.644, 0.645, 0.662
      and 0.655 for DC0, HSC2, MSC2, XFC0 and XFC1, respectively. All these results
      mean that after selection the ranges of variance of the populations decreased
      slightly. And the mean genetic distance calculated from the 185 alleles were
      0.4695, 0.4696, 0.4698, 0.4836 and 0.4902 for DC0, HSC2, MSC2, XFC0 and XFC1,
      respectively. There was nearly no difference after selection in both the basic
      populations. Analyses on the distribution of genetic distance showed that most of
      the genetic distances in the developed populations were smaller than in the basic
      populations. But the ranges of the genetic distance were wider after selection in
      both populations. This result indicated that heterogeneity between some of the
      individuals in the developed populations increased after several times of
      recombination and exchange. All these indexes demonstrated that the genetic
      diversity of selection populations was similar to their primary populations, and
      genetic variation was maintained during recurrent selection.

PMID- 15468923
TI  - [Molecular identification of wheat granule bound starch synthase gene
      polymorphism].
AB  - Fourteen wheat cultivars were identified into six types of Wx proteins
      combinations using 6% SDS-PAGE. PCR primers were designed according to the three
      Wx genes sequences and their mutants, respectively. A 327 bp-band was amplified
      from the Wx-A1 mutant,while the band was absent for the normal alleles at the Wx
      A1 locus,as well as the presence or absence of a 187 bp PCR fragment at the Wx-B1
      locus and a 700 bp PCR fragment at the Wx-D1 locus, respectively, corresponding
      to the normal and mutant alleles. Compared with the former studies, shorter and
      more different PCR products at three loci, amplified by the primers designed for
      Wx-B1 gene can be separated in 2% agarose gel, which enables screening breeding
      lines for noodle use faster and effectively.

PMID- 15468924
TI  - [Mapping of five genes resistant to SMV strains in soybean].
AB  - Soybean mosaic virus (SMV) is one of the most prevalent pathogens that impact the
      soybean world widely. Previous reports showed that most of the resistances were
      controlled by one pair of dominant genes. In this study, a soybean RIL population
      NJRIKY derived from Kefeng 1 x Nannong 1138-2 was used to study the inheritance
      of resistance to five SMV strains (Sa,Sc-8, Sc-9, N1, and N3) and mapping of
      resistant genes. Kefeng 1 is resistant to all five SMV strains while Nannong 1138
      2 is susceptible to all five SMV strains. The parents and RIL populations were
      planted in green house and five SMV strains were inoculated on different
      populations. The results showed that each ratio of the number of resistant
      families to that of susceptible families was consistent with 1:1 for the five
      strains. This indicated that the resistance to each of the five strains was
      controlled by one dominant gene, respectively. RFLP and SSR markers were used to
      analyze the RIL population, Mapmaker/Exp 3.0b was used to study the linkage
      between markers and the resistant genes. Through linkage analysis, Rsa was found
      linked Rn1, Rn3 and Rsc9 with 21.4 cM, 23.5 cM and 35.3 cM, Rsc8 was found to be
      linked only Rn1 with 35.8 cM. Multi locus analysis showed that the order and
      intervals of the five resistance genes were Rsc8-35.8 cM-Rn1-10.3 cM-Rn3-21.5 cM-
      Rsa-35.8 cM-Rsc9. According to the result of RFLP and SSR analysis, a genetic map
      was constructed which consisted of 256 markers that covered 3050.9 cM and
      converged into 22 linkage groups. The five resistance genes were mapped on the
      linkage group N8-D1b + W. The RFLP markers A691T, K4771, LC5T were found linked
      to the resistant genes Rn1 and Rn3 with distances of 15.04 cM, 17.82 cM, 15.37
      cM, 16.14 cM, 17.82 cM, 16.58 cM.

PMID- 15468925
TI  - [Positional analysis of a gene related to salt tolerance in Sinorhizobium
      meliloti by transposon rescue].
AB  - Salt sensitive mutant 042BML-2 was obtained by mutating Sinorhizobium meliloti
      042BM with transposon Tn5 carried on the plasmid pRL1063a. By transposon rescue,
      a 1.179 kb of DNA sequence of S. meliloti flanking the Tn5 insertion site was
      obtained. The sequence similarity analysis through BLAST analysis in GenBank
      revealed the transposon was inserted into a functionally unknown gene, which is 6
      270 bp in length, of S. meliloti, and the gene was named rtsC. This study
      indicated that rtsC was associated with salt tolerance in S. meliloti 042BM.
      Hydrophobicity profile analysis of the putative amino acid sequence showed that
      two predicted transmembrane domains existed in N-terminal portion of RtsC. The
      significance of RtsC protein in the salt-tolerance in S. meliloti was discussed.

PMID- 15468926
TI  - [Saline tolerance white clover transformed with the betaine aldehyde dehyrogenase
      gene by Agrobacterium tumefaciens].
AB  - The white clover has been transformed with the Betaine Aldehyde Dehydrogenase
      (BADH) gene cloned from Atriplex hortensis by Agrobacterium tumefaciens. The
      relative electronic conductivity of the transgenic plants under 1% NaCl stress
      for 48 hours was about 20%, less than the control plant's relative electronic
      conductivity (more than 40%), these showed the cell membrane of the transgenic
      plants has been less injured than control plants under salt stress. The other
      experience showed that the transgenic plant could grow well in water culture
      included 0.5% NaCl for more than two weeks, but the control plants could not.

PMID- 15468927
TI  - [Molecular mechanism of mRNA alternative splicing].
AB  - Eukayotic pre-mRNAs are spliced to form mature mRNA. The pre-mRNAs alternative
      splicing greatly increases the diversity of proteins and the complexity of genes
      expression. The recognition of splice sites can occur across intron (intron
      definition) or across exon (exon definition). There are many kinds of alternative
      splicing patterns, including the choice of alternative splicing sites, the choice
      of alternative splicing ends, the alternative splicing of mutually exclusive
      exons, and an intron can be excised from or retained in mRNA. The splice sites
      choice process is regulated by many kinds of cis-acting and trans-acting elements
      and is closely related with the basic splicing process. Some of the splicing
      factors in basic splicing process can regulate the alternative splicing. The
      alternative splicing is also a co-transcriptional process. Promoters can regulate
      alternative splicing and produce different mRNA isoforms. Many molecular
      mechanisms of alternative splicing have been proposed, and it was also found that
      the RNA editing and trans-splicing could also regulate alternative splicing.

PMID- 15468928
TI  - [Development of monoclonal-based enzyme-linked immunosorbent assay and
      immunochromatographic assay for lasalocid and semduramicin].
AB  - Monoclonal antibodies (MAbs) against lasalocid and semduramicin were prepared
      using keyhole limpet hemocyanin conjugates for the immunization of mice. With
      these MAbs, we developed quantitative enzyme-linked immunosorbent assay (ELISA)
      methods for lasalocid and semduramicin. The ELISAs were quantitative in the
      ranges of 0.1-50 ng/mL for lasalocid and 0.05-12.5 ng/mL for semduramicin, and
      showed 50% inhibition concentrations of 1.2 ng/mL for lasalocid and 0.5 ng/mL for
      semduramicin. The coefficient of variations (CV%) of lasalocid were 0.3-4.4% for
      intra-assay and 0.5-5.1% for inter-assay and those of semduramicin were 0.1-4.6%
      for intra-assay and 0.3-5.2% for inter-assay. The detection limits for lasalocid
      and semduramicin were 10 ng/g and 5 ng/g in chicken liver and muscle,
      respectively. Based on the immunochromatographic method, rapid test kits for
      lasalocid and semduramicin were also developed. With these kits, the detection
      limits of lasalocid were 50 ng/mL for standard solution and 125 ng/g for chicken
      muscle, and those of semduramicin were 10 ng/mL for standard solution and 100
      ng/g for chicken muscle.

PMID- 15468929
TI  - [Detection method of injured Escherichia coli O157 in noodles and vegetables].
AB  - An enrichment procedure and a polymerase chain reaction (PCR) method for the
      detection of injured Escherichia coli O157 in foods were examined. Freeze-injured
      E. coli O157 inoculated in boiled spaghetti could be detected in 6-h culture
      within 12 h by the PCR method. Cells injured by heating in boiled spaghetti and
      cells injured by chlorine treatment in raw lettuce and carrot did not grow
      sufficiently to be detected in 6-h culture but were detected in 18-h culture
      using selective agar media. The injured cells could be also detected in 18-h
      culture within 24 h by the PCR method. Enrichment at 42 degrees C in trypticase
      soy broth (TSB) was more effective than that at 42 degrees C in modified EC broth
      with novobiocin. These results indicated that the usage of enrichment in TSB for
      18 h at 42 degrees C in combination with the PCR method is suitable for screening
      for E. coli O157 in boiled or chlorinated foods, even if the O157 cells are
      injured.

PMID- 15468930
TI  - [Inter-laboratory evaluation studies for development of notified ELISA methods
      for allergic substances (milk)].
AB  - Extracts of sausage, sauce, cookie, cereal and pasta sauce spiked with milk
      standard protein at a level of 5-20 ng/mL as sample solutions were analyzed in
      replicate in 10 laboratories. Coefficients of variation (CVs) of the three ELISA
      methods using a Milk Protein Casein ELISA Kit (Casein kit), a Milk Protein Beta
      Lactoglobulin ELISA Kit (Beta-Lactoglobulin kit) and a FASTKIT Milk ELISA Kit
      (Milk ELISA kit) were mostly below 10%. Mean recoveries of the milk standard
      protein from the food extracts were over 40% in the three ELISA methods with a
      few excertions. The recoveries of milk standard protein from the sauce extract in
      Casein kit were improved by adjusting the extract to neutrality before the Casein
      kit assay. The recoveries of milk standard protein from cookie, cereal and pasta
      sauce were improved by the increasing the amount of antibody coated in the Milk
      ELISA kit. The detection limits of all the ELISA methods were 1 ng/mL in sample
      solutions. These results suggested that the notified ELISA methods are reliable
      and reproducible for the inspection of milk protein levels in extracts of
      sausage, sauce, cookie, cereal and pasta sauce.

PMID- 15468932
TI  - [Determination of carbadox metabolites, quinoxaline-2-carboxylic acid and
      desoxycarbadox, in swine muscle and liver by liquid chromatography/mass
      spectrometry].
AB  - A sensitive and selective method using liquid chromatography-electrospray mass
      spectrometry (LC-ESI-MS) for the determination of carbadox metabolites,
      quinoxaline-2-carboxylic acid (QCA) and desoxycarbadox (Desoxy-CDX), in swine
      muscle and liver has been developed. The LC separation was performed on a Cadenza
      CD-C18 column (10 cm x 2 mm i.d.) with a gradient system of 0.01% acetic acid
      acetonitrile as the mobile phase at a flow rate of 0.2 mL/min. Negative
      ionization produced the [M-H]- molecular ion of QCA. On the other hand, the
      positive mode produced the [M+H]+ ion of Desoxy-CDX. The calibration graphs for
      QCA and Desoxy-CDX were rectilinear from 0.01 to 0.5 ng with selected ion
      monitoring (SIM). The drugs were extracted with 0.3% metaphosphoric acid-methanol
      (7:3), and the extracts were cleaned up on an Oasis HLB cartridge (60 mg) and by
      liquid-liquid extraction. The recoveries of QCA and Desoxy-CDX from swine muscle
      and liver fortified at 2.5 and 5 ng/g were 70.2-86.3%, and the detection limits
      were 1 ng/g for both drugs.

PMID- 15468931
TI  - [Inter-laboratory evaluation studies for development of notified ELISA methods
      for allergic substances (wheat)].
AB  - Extracts of sausage, sauce, pasta sauce, fish paste and cereal spiked with wheat
      standard protein at a level of 5-20 ng/mL as sample solutions were analyzed in
      replicate in 10 laboratories. Coefficients of variation (CVs) of both ELISA
      methods using a Wheat Protein ELISA Kit (Gliadin kit) and a FASTKIT Wheat ELISA
      Kit (Wheat ELISA kit) were mostly below 10%. Mean recoveries of the wheat
      standard protein from the food extracts were over 40% in the two ELISA methods
      except those from cereal extract determined using the Wheat ELISA kit.
      Repeatability relative standard deviations of wheat standard protein in the five
      food extracts were in the ranges of 16-26.9% and 3.7-36.2% for the Gliadin kit
      and the Wheat ELISA kit, respectively. Reproducibility relative standard
      deviations of wheat standard protein in the five food extracts were 21.6-38.5%,
      29.7-53.8% for the Gliadin kit and the Wheat ELISA kit, respectively. The
      recoveries of wheat standard protein from the cereal extract were improved by the
      increasing the amount of antibody coated on the plate in the Wheat ELISA kit. The
      detection limits of both ELISA methods were 1 ng/mL in sample solutions. These
      results suggested that the notified ELISA methods are reliable and reproducible
      for the inspection of wheat protein levels in extracts of sausage, sauce, pasta
      sauce, fish paste and cereal.

PMID- 15468933
TI  - Investigation of spectrophotometrically determined substances in Yucca extract by
      GC/MS, TLC and on-column injection GC.
AB  - Spectrophotometrically determined substances in Yucca extract, listed as "Yucca
      foam extract" in the "List of Existing Food Additives in Japan", were
      investigated by GC/MS, TLC and GC. A TLC method using an anisaldehyde color
      developing reagent similar to that employed in spectrophotometry was established
      for selective detection of sapogenins in Yucca extract. Several steroidal
      sapogenins were found by GC/MS in the fractions corresponding to spots on the TLC
      plate, and these were assumed to have contributed to the color development in
      spectrophotometry. Sarsasapogenin and smilagenin were the dominant sapogenins. An
      on-column injection GC method to determine these sapogenins in Yucca extract was
      also developed. The sum of these two sapogenins in Yucca extract was 0.9%. The
      total amount of sapogenin estimated by GC was approximately 2%, which was similar
      to that measured by spectrophotometry.

PMID- 15468934
TI  - [Toxicity of puffer fish cultured in netcages].
AB  - During 1990 to 2003, the toxicity of the liver in 4,515 specimens of the puffer
      fish Takifugu rubripes (torafugu) cultured in netcages or on land were
      investigated by means of mouse bioassay and liquid chromatography-mass
      spectrometry (LC/MS). Other tissues (skin, muscles, gonads, etc.) were also
      investigated in some of them. All the livers and other parts examined were found
      to be non-toxic. The peak corresponding to tetrodotoxin (TTX) was not detected in
      the samples by LC/MS analysis for TTX (< 0.1 MU/g). These results show that
      puffer fish fed on a non-toxic diet in netcages do not become intoxicated.

PMID- 15468935
TI  - [Determination of synthetic food dyes in food by capillary electrophoresis].
AB  - A method for the determination of 12 synthetic food dyes (Amaranth, Erythrosine,
      Allura Red AC, New Coccine, Phloxine, Rose Bengal, Acid Red, Tartrazine, Sunset
      Yellow FCF, Fast Green FCF, Brilliant Blue FCF, Indigo Carmine) in food was
      developed using capillary electrophoresis (CE) with photodiode array detection.
      The dyes were extracted with water and 0.5% ammonia-ethanol (1:1) mixture, and
      cleaned up using solid-phase extraction (Sep-Pak Plus tC18). The dyes were eluted
      with methanol from the cartridge. The dyes were separated by CE on a bubble cell
      fused-silica capillary (72 cm to the detector, 75 microm i.d.) using 20%
      acetonitrile in a mixture of 10 mmol/L potassium phosphate, monobasic and 5
      mmol/L sodium carbonate (pH 10.0) as the running buffer. Identifications of the
      dyes were performed on the basis of the migration time and the absorbance
      spectrum of each peak. The coefficients of variation of the migration times and
      the peak areas were 0.28-0.62% and 1.84-4.30%, respectively (n = 5). The
      identification limits using the absorbance spectra of the dyes were 10 microg/mL
      for Brilliant Blue FCF and Fast Green FCF, and 5 microg/mL for the other 10 dyes.
      The recoveries of the 12 dyes from pickles, soft drinks and candies at the level
      of 10 microg/g were 70.0-101.5%. The method was applied to the analysis of dyes
      in foods. The dyes detected by CE were in agreement with those detected by paper
      chromatography.

PMID- 15468937
TI  - [Simultaneous determination of residual fourteen kinds of beta-lactam and
      macrolide antibiotics in bovine muscles by high-performance liquid chromatography
      with a diode array detector].
AB  - Residues of 14 kinds of beta-lactam and macrolide antibiotics in bovine muscles
      were extracted with acetonitrile and the extract was partitioned with n-hexane to
      remove fat. High-performance liquid chromatography was carried out on a TSK-gel
      ODS-80TM column using gradient elution with acetonitrile-0.05% trifluoroacetic
      acid and the drugs were quantitated by diode array detection. The recoveries of
      the drugs from bovine muscles spiked at 0.1 ppm were over 63% and each
      quantitation limit was 0.04 ppm.

PMID- 15468936
TI  - [Evaluation of three commercial ELISA kits for rapid screening of deoxynivalenol
      in unpolished wheat].
AB  - Evaluation of commercial ELISA kits for the screening of deoxynivalenol (DON) was
      carried out. Three kinds of commercial kits supplied by different companies were
      used. Three lots of naturally contaminated wheat and DON-free wheat (<0.05
      microg/g) were used as samples. The values obtained from ELISA were compared with
      those of the HPLC-UV method. In the results obtained from 14 institutions using
      ELISA, the CV values were less than 17.6% for all the commercial kits. The DON
      free sample was not detected as positive with any commercial kits. Also there was
      no negative finding among the naturally contaminated samples used in this
      experiment. Coefficients of determination in ELISA and HPLC analysis were 0.979
      0.999. These results indicate that ELISA using any of the three commercial kits
      is efficient for the screening of DON in wheat.

PMID- 15468938
TI  - [Evaluation of method for simultaneous determination of pesticide residues in
      fruits and vegetables by collaborative study].
AB  - A collaborative study involving 8 laboratories was conducted to evaluate a method
      for the simultaneous determination of pesticide residues in 6 types of fruits and
      vegetables (spinach, tomato, apple, radish, cabbage and carrot). The method of
      analysis was the same as reported by Kakimoto et al. in 2003. One hundred and
      thirty-nine pesticides were spiked by each of 8 laboratories at levels of 0.1
      microg/g (pesticides analyzed by GC/MS) or 0.5 microg/g (pesticides analyzed by
      HPLC) into the 6 kinds of samples. Statistical analysis showed that 111
      pesticides could be analyzed with practical precision by this method. For
      screening purposes, the method could analyze 118 pesticides. The median values of
      the limits of detection were 0.001-0.041 microg/g. The calibration curves were
      linear in the range of 0.5-5 microg/mL for most pesticides with median
      correlation coefficients of 0.983-1.000.

PMID- 15468939
TI  - Study of arsenic trioxide-induced vascular shutdown and enhancement with
      radiation in solid tumor.
AB  - PURPOSE: Arsenic trioxide (ATO) has been reported to be an effective
      chemotherapeutic agent for acute promyelocytic leukemia (APL), and, recently,
      anti-tumor effect has been demonstrated in solid tumors. However, little is known
      about the mechanism of action of the ATO effect on solid tumor. We investigated
      the anti-vascular effect of ATO and the potential of combining ATO with radiation
      therapy. MATERIALS AND METHODS: We studied the anti-vascular effect of ATO and
      radiosensitization of squamous cell carcinoma (SCC) VII murine tumors of C3H
      mice. The anti-vascular effect was examined using magnetic resonance
      imaging(MRI), and radiosensitivity was studied by clonogenic assay and tumor
      growth delay. Histopathological changes of the tumors after various treatments
      were also observed with hematoxylin and eosin (H&E) staining. RESULTS: Necrosis
      and blood flow changes in the central region of tumors in the hind limbs of the
      animals were observed on T2-weighted imaging after an i.p. injection of 8 mg/kg
      of ATO alone. ATO exposure followed by radiation decreased the clonogenic
      survival of SCC VII cells compared with either treatment alone. Tumor growth
      delay after 10-20 Gy of radiation alone was increased slightly compared with
      control tumors, but the combination of ATO injection 2 hours before exposure to
      20 Gy of radiation significantly prolonged tumor growth delay by almost 20 days.
      CONCLUSION: The results suggest that ATO and radiation can enhance the
      radiosensitivity of solid tumor.

PMID- 15468940
TI  - Utility of cine MR urography of the urinary tract and comparison with static MR
      urography.
AB  - PURPOSE: MR urography using heavily T2-weighted images can depict the urinary
      tract without the need for contrast medium. However, this technique has potential
      problems with regard to evaluating the non-dilated ureter. We compared the
      efficacy of cine MR urography (C-MRU) with static MR urography (S-MRU). MATERIALS
      AND METHODS: Twenty-two patients with suspected upper urinary tract disease
      underwent C-MRU. The final clinical diagnosis was compared with the diagnosis
      made using S-MRU and C-MRU, respectively. The sequence used was single-shot fast
      spin echo with a slice thickness of 50 mm, FOV of 45 cm, and 256x256 matrix. MR
      urography was obtained sequentially by 6 to 10 repetitions of single-shot scans
      with intermittent breath holding. S-MRU was used in the initial phase of this
      sequence, while C-MRU was used for the entire sequence. A final diagnosis was
      made based on 1) existence of stenosis, 2) rate of certainty of existence of
      stenosis, 3) etiology of stenosis. RESULTS: No statistically significant
      difference was observed between S-MRU and C-MRU, except in certainty of existence
      of stenosis, where C-MRU (average rate: 2.82 +/- 0.39) was significantly superior
      to S-MRU (2.41 +/- 0.73). CONCLUSION: C-MRU can improve the certainty of
      existence of urinary stenosis, and may be useful in excluding suspected stenoses
      in normal or undilated ureters.

PMID- 15468941
TI  - New CR system with pixel size of 50 microm for digital mammography: physical
      imaging properties and detection of subtle microcalcifications.
AB  - PURPOSE: To investigate the physical imaging properties and detection of
      simulated microcalcifications of a new computed radiography (CR) system with a
      pixel size of 50 microm for digital mammography. MATERIALS AND METHODS: New and
      conventional CR were employed in this study. The new CR system included a high
      resolution imaging plate coupled with the FCR5000MA (50 microm pixel pitch)
      including transparent support and a dual-sided reader. The conventional CR system
      was coupled with the FCR9000 (100 microm pixel pitch). Modulation transfer
      functions (MTFs) and Wiener spectra (WS) of the new and conventional CR systems
      were measured. Observer performance tests were conducted to compare the effects
      of pixel size (50 microm vs. 100 microm) on the diagnostic accuracy of CR systems
      in the detection of simulated microcalcifications. RESULTS: The presampling MTF
      of the new CR system was higher at high frequencies than the conventional CR
      system. The WS of the new CR system was comparable to that of the conventional CR
      system at all frequencies. The area under the receiver operating characteristic
      (ROC) curve (Az) obtained with the new CR and the conventional CR systems were
      0.84 and 0.79, respectively. Results showed that the detection of simulated
      clustered microcalcifications was significantly improved by use of the new CR
      system compared with the conventional CR system (p<0.05). CONCLUSION: The new CR
      mammography system improved physical imaging properties and detection of
      simulated microcalcifications over conventional CR mammography.

PMID- 15468942
TI  - Increased radiation dose by automatic exposure control system during fluoroscopy
      and angiography of pelvis due to contrast material in the bladder: experimental
      study.
AB  - PURPOSE: To evaluate the increase of radiation dose caused by contrast material
      excreted in the bladder during vascular interventional procedures of the pelvis.
      MATERIALS AND METHODS: A latex balloon filled with diluted contrast material,
      simulating the bladder, was placed in a water phantom. Entrance dose rates were
      measured under various conditions with and without the balloon. In animal
      experiments, skin doses during fluoroscopy and angiographic image acquisitions
      were measured at the pelvis of a swine before and after the contrast was excreted
      in the bladder. RESULTS: In phantom experiments, fluoroscopic dose rates
      increased 1.3- to 3.9-fold when the contrast-filled balloon was placed at the
      periphery of the phantom. The dose rates increased 3.0- to 4.0-fold when the
      balloon was placed at the center. In the animal experiment, dose rates increased
      1.4- to 2.0-fold when the bladder was filled with contrast material. Skin doses
      during 10-second angiographic image acquisition also increased 1.1- to 2.3-fold
      when the bladder was filled with contrast. CONCLUSION: When the bladder is filled
      with excreted contrast material, skin doses delivered by fluoroscopy and
      angiography will increase. Removal of urine is recommended during vascular
      interventional procedures of the pelvis.

PMID- 15468943
TI  - Effects of density changes in the chest on lung stereotactic radiotherapy.
AB  - To experimentally and theoretically evaluate dose distribution during lung
      stereotactic radiotherapy, we investigated the relative electron densities in
      lung and tumor tissues using X-ray computed tomography images obtained from 30
      patients in three breathing states: free breathing, inspiration breath-hold, and
      expiration breath-hold. We also calculated dose distribution using Monte Carlo
      simulation for lung tissue with two relative electron densities. The effect of
      changes in relative electron density on dose distribution in lung tissue was
      evaluated using calculated differential and integral dose volume histograms. The
      relative electron density of lung tissue was 0.22 in free breathing, 0.23 in
      shallow expiration, and 0.17 in shallow inspiration, and there was a tendency for
      relative electron density to decrease with age. The relative electron density of
      tumor tissue was approximately 0.9, with little variation due to differences in
      breathing state. As the relative electron density of lung tissue decreases, the
      low-dose region expands and leads to changes in the marginal dose.

PMID- 15468947
TI  - CT and MR findings of basal cell adenoma of the parotid gland.
AB  - We report a case of basal cell adenoma in the left parotid gland. A 34-year-old
      woman presented with a non-tender mass in the left parotid gland. She had first
      noted it 7- years previously, and it had been gradually increasing in size. The
      tumor was well-circumscribed with a smooth contour. On noncontrast-enhanced CT,
      the tumor showed homogeneous soft tissue attenuation. No cystic portion or
      calcification was seen. The tumor showed homogeneous moderate enhancement on
      contrast-enhanced CT. Capsule-like ring enhancement was demonstrated. On T1
      weighted MR imaging, the tumor was homogeneously hypointense to the surrounding
      parotid tissue and isointense to muscle. On T2-weighted imaging the tumor was
      homogeneously hyperintense to muscle but slightly hypointense to the surrounding
      parotid tissue. On Gd-enhanced T1-weighted imaging, the tumor demonstrated
      homogeneous moderate enhancement. Capsule-like ring enhancement was also
      demonstrated. Salivary (technetium-99m-pertechnetate) scintigraphy did not show
      any uptake in the tumor.

PMID- 15468945
TI  - Histologic breast cancer extent after neoadjuvant chemotherapy: comparison with
      multidetector-row CT and dynamic MRI.
AB  - PURPOSE: To evaluate the efficacy of dynamic multidetector-row CT (MDCT) in
      assessing residual cancer extent after neoadjuvant chemotherapy (NAC), and to
      compare MDCT results with those derived from dynamic three-dimensional MRI using
      the volumetric interpolated breath-hold examination (VIBE) sequence. MATERIALS
      AND METHODS: MDCT before and after NAC was performed in 19 consecutive patients
      with breast cancer. MRI was also performed before surgery. The early phase of
      MDCT and MRI was started 60 sec after commencing contrast injection. The late
      phase was started at a 4-min delay from the injection. The injection rate was 3
      mL/sec. The distribution pattern of contrast enhancement (CE) by CT before NAC
      was classified into two groups: replaced lesion (diffuse CE in whole quadrants)
      and non-replaced lesion (localized CE). RESULTS: Pathological complete response
      (pCR) was obtained in one case. In replaced lesions, accuracy for the detection
      of tumor extent with a deviation of less than 2 cm in length was 0% (0/7) with
      early-phase CT/MRI and 100% (7/7) with late-phase CT/MRI. In non-replaced
      lesions, accuracy was 55% (6/11) with early-phase CT/MRI and 82% (9/11) with late
      phase CT/MRI. One case of ductal carcinoma in situ (DCIS) could be detected only
      with late phase MRI. CONCLUSION: Late-phase images obtained by MDCT and MRI may
      be accurate in the diagnosis of residual cancer extent after NAC. The tumor
      distribution determined by MDCT before NAC is thought to be useful in the
      evaluation of shrinkage pattern following NAC.

PMID- 15468944
TI  - Multi-detector row helical CT of the liver: quantitative assessment of iodine
      concentration of intravenous contrast material on multiphasic CT--a prospective
      randomized study.
AB  - PURPOSE: The purpose of this study was to assess the quantitative effects of
      contrast material concentration on hepatic parenchymal and vascular enhancement
      in multiphasic computed tomography (CT), using multi-detector row helical CT.
      MATERIALS AND METHODS: We designed a prospective randomized study to test two
      different concentrations of contrast material on five phasic scans of the liver.
      One hundred patients were randomly assigned to two groups: an iodine
      concentration of 300 mg/mL in group A and 370 mg/mL in group B. All patients
      received a fixed volume of 100 mL at a 4 mL/sec injection rate. Enhancement
      values for the hepatic parenchyma and aorta at three levels (upper, middle, and
      lower level of the liver), and values for portal and hepatic veins were
      statistically compared between the two groups. RESULTS: Hepatic parenchymal
      enhancement values at all levels of the liver in portal phase (PP) and
      equilibrium phase (EP) were significantly higher in group B than in group A
      (p<0.01). Aortic enhancement values at two levels of the liver (middle and lower)
      in early hepatic arterial phase (EAP) were significantly higher in group B than
      in group A (p<0.05), however, there was no significant difference between groups
      A and B in aortic enhancement during the delayed hepatic arterial phase (DAP).
      Portal and hepatic venous enhancement values in PP and EP were significantly
      higher in group B than in group A (p<0.01). CONCLUSION: On multiphasic dynamic
      CT, the use of a higher iodine concentration of contrast material results in
      higher hepatic parenchymal enhancement and aortic enhancement, as well as higher
      portal and hepatic venous enhancement.

PMID- 15468946
TI  - Intraarterial infusion chemotherapy for head and neck cancers: evaluation of
      tumor perfusion with intraarterial CT during carotid arteriography.
AB  - PURPOSE: To evaluate drug distribution in carcinomas of the head and neck region
      with CT during intraarterial contrast-material injection for superselective
      intraarterial infusion of anti-cancer agents, and to evaluate perfusion in the
      carcinomas with intraarterial dynamic CT, using a combined CT and angiography
      system. MATERIALS AND METHODS: Twenty-three consecutive patients underwent
      conventional angiography as well as intraarterial injection CT using a combined
      CT and angiography system. Contrast material enhancement on intraarterial CT
      images was evaluated qualitatively and quantitatively with the following
      parameters: enhanced pattern, delineation and extent of tumor, peak CT value,
      peak time, maximum inclination of wash-in and washout, and transfer index (k)
      using a Patlak plot method. After the feeding vessels had been identified by
      enhancement of the tumor on CT of the selected vessel, relatively low-dose
      cisplatin was injected through the microcatheter placed in each artery depending
      on tumor location. Histopathologic effects were evaluated after surgery and
      compared with CT findings. RESULTS: In the qualitative evaluation, tumors showed
      early, strong enhancement as well as rapid washout compared with the adjacent
      normal tissues, and dynamic CT was useful for evaluation of the extent of the
      tumor. When multiple feeders existed, the dose of cisplatin for each feeder could
      be determined by the percentage of tumor enhanced with CT on each vascular
      injection. The mean values of quantitative parameters, however, were not
      significantly different between the good and poor response groups. CONCLUSION:
      Intraarterial CT was useful for evaluation of the arterial supply and drug
      distribution of the tumor. However, quantitative data did not provide additional
      information for prediction of the treatment effect. This might indicate that the
      effectiveness of intraarterial chemotherapy is not directly related to the
      perfusion of head and neck cancers.

PMID- 15468948
TI  - Brown tumor of the sphenoid sinus in a patient with secondary
      hyperparathyroidism: CT and MR imaging findings.
AB  - We present a case of brown tumor of the sphenoid sinus in a patient with
      secondary hyperparathyroidism. CT showed an expansile soft-tissue attenuation
      mass centered in the sphenoid sinus. CT at bone window setting demonstrated
      expansile, lytic change and remodeling of the surrounding bone. On MR imaging,
      the lesion showed iso-intensity to gray matter on T1-weighted images and
      heterogeneous hyperintensity on T2-weighted images, and showed intense
      enhancement. The extent of the lesion and its relationship to the surrounding
      structures were best evaluated by CT and MR imaging.

PMID- 15468949
TI  - Iatrogenic venous air embolism caused by CT injector--from a risk management
      point of view.
AB  - An iatrogenic venous air embolism caused by computed tomography (CT) injector
      occurred in a 74-year-old man undergoing abdominal-pelvic CT for evaluation of an
      abdominal aortic aneurysm (AAA). During the initial inspection scan of the
      thoracic part, a large amount of air was detected in the right ventricle, but no
      contrast medium was noted in the aorta. Surface oxygen was given immediately, and
      the patient was placed in the left lateral decubitus position on the CT bed.
      During that time he had no symptoms except coughing. CT revealed no air in the
      brain or pulmonary vein, and he was returned to his room 55 minutes after the
      incident. There were no complications during a six-month follow-up period. The
      importance of daily risk management and immediate proper after care to prevent
      such accidents was reconfirmed.

PMID- 15468950
TI  - Early ureteral luminal enhancement on computed tomography in a renal trauma
      patient: a characteristic sign of communication between artery and collecting
      system.
AB  - We report the case of a 65-year-old man with blunt abdominal trauma following a
      fall from a three-meter-high roof. Contrast-enhanced abdominal computed
      tomography (CT) obtained in early phase showed intense contrast enhancement in
      the urinary tract as dense as artery. This finding was considered characteristic
      of traumatic communication between artery and collecting system. In cases of
      blunt abdominal trauma, contrast-enhanced CT should be obtained in the early
      phase to diagnose this disorder. When the diagnosis is made, prompt treatment
      should be initiated.

PMID- 15468952
TI  - Constants and variables in immunohistochemistry.
AB  - Many efforts have been made to develop reliable methods for the quantification of
      immunohistochemical reaction products. Most of the corresponding studies have
      dealt with problems related to the development of adequate hardware and software,
      while fewer investigations have focused on variables of histotechnical or
      immunohistochemical methods. The present paper summarizes findings and experience
      obtained over many years in this latter field, and a total of 14 corresponding
      parameters were considered. The studies were performed with methods well
      established in the author's laboratory; namely immunohistochemistry for various
      pancreatic hormones and chromogranin A applying the peroxidase anti-peroxidase
      method on serial semithin sections from the mammalian endocrine pancreas. Optical
      densities of immunoreactivities were determined using an appropriate measuring
      program by the interactive image analysis system IBAS. All parameters
      investigated were found to influence densities of immunoreactivities, and those
      with major significance were: 1) the thickness of histologic sections; 2) the
      dilution range of the antisera used as first layers; 3) the type or composition
      of the buffers used for dilution of the antisera and of the chromogen di
      aminobenzidine or as the rinsing solution. All these variables could be
      standardized in appropriate ways. It was not possible, however, to prevent batch
      to-batch (inter-assay) variations. Finally, the results of the present
      investigations served to increase the efficiency of immunohistochemical staining
      by the applied methods.

PMID- 15468951
TI  - Diffusion weighted whole body imaging with background body signal suppression
      (DWIBS): technical improvement using free breathing, STIR and high resolution 3D
      display.
AB  - PURPOSE: To examine a new way of body diffusion weighted imaging (DWI) using the
      short TI inversion recovery-echo planar imaging (STIR-EPI) sequence and free
      breathing scanning (diffusion weighted whole body imaging with background body
      signal suppression; DWIBS) to obtain three-dimensional displays. MATERIALS AND
      METHODS: 1) Apparent contrast-to-noise ratios (AppCNR) between lymph nodes and
      surrounding fat tissue were compared in three types of DWI with and without
      breath-holding, with variable lengths of scan time and slice thickness. 2) The
      STIR-EPI sequence and spin echo-echo planar imaging (SE-EPI) sequence with
      chemical shift selective (CHESS) pulse were compared in terms of their degree of
      fat suppression. 3) Eleven patients with neck, chest, and abdominal malignancy
      were scanned with DWIBS for evaluation of feasibility. Whole body imaging was
      done in a later stage of the study using the peripheral vascular coil. RESULTS:
      The AppCNR of 8 mm slice thickness images reconstructed from 4 mm slice thickness
      source images obtained in a free breathing scan of 430 sec were much better than
      9 mm slice thickness breath-hold scans obtained in 25 sec. High resolution multi
      planar reformat (MPR) and maximum intensity projection (MIP) images could be made
      from the data set of 4 mm slice thickness images. Fat suppression was much better
      in the STIR-EPI sequence than SE-EPI with CHESS pulse. The feasibility of DWIBS
      was showed in clinical scans of 11 patients. Whole body images were successfully
      obtained with adequate fat suppression. CONCLUSION: Three-dimensional DWIBS can
      be obtained with this technique, which may allow us to screen for malignancies in
      the whole body.

PMID- 15468953
TI  - The expression of src-suppressed C kinase substrate (SSeCKS) and uptake of
      exogenous particles in endothelial and reticular cells.
AB  - Src-suppressed C kinase substrate (SSeCKS), a potent tumor suppressor, plays a
      role in membrane-cytoskeletal remodeling to regulate mitogenesis, cell
      differentiation, and motility. Our previous study showed that lipopolysaccharide
      (LPS) induced a selective and strong expression of SSeCKS in the vascular
      endothelial cells of several organs, such as hepatic sinusoids, and in the
      reticular cells of lymphoid organs. In the present immunocyto-chemical study, we
      determined the detailed cellular and subcellular localization of SSeCKS in mouse
      tissues after LPS administration, and examined the involvement of SSeCKS in the
      uptake of exogenous particles. SSeCKS immunoreactivity in the liver and lymph
      nodes was below the detectable level under normal conditions. After LPS
      stimulation, an intense immunoreactivity for SSeCKS became noticeable in
      sinusoidal endothelial cells of the liver and medullary reticular cells of the
      lymph node. Electron-microscopically, the immunoreactivity was localized
      predominantly along the cytoplasmic membrane of both cell types. These cells in
      normal mice incorporated a small amount of injected particles (carbon particles
      and latex beads), while after LPS stimulation, the uptake of particles increased
      in terms of the amount and extent of the uptaking sites. Endothelial cells and
      reticular cells without SSeCKS expression could not incorporate any particles
      even after LPS stimulation. The subcellular localization of SSeCKS in endothelial
      cells correlated with some pinocytic pits and phago-lysosomes, although a diffuse
      distribution of SSeCKS in the cytoplasm was also visible. Taken together, these
      findings indicate that SSeCKS expression in endothelial cells and reticular cells
      is a functional index of the reticulo-endothelial system and is involved in the
      uptake of particles from blood and lymph circulation.

PMID- 15468954
TI  - Morphological and immunohistochemical changes to thymic epithelial cells in the
      irradiated and recovering rat thymus.
AB  - The present study analyzed morphological and immunohistochemical changes of
      thymic epithelial cells in the irradiated and recovering rat thymus. Observations
      showed the number of thymocytes was initially severely reduced after irradiation
      but abruptly increased on days 3 to 5 after 6 Gy and on days 7 to 11 after 8 Gy
      irradiation. To analyse the mechanisms for this abrupt recovery of the thymocytes
      after irradiation, the expression of p63 in the normal and irradiated thymus was
      immunohistochemically studied as the expression of this antigen may be related to
      the proliferation of epithelial cells. In the fetal thymus tissue, thymic
      epithelial cells were the principal cell type that stained strongly positive for
      p63. The sporadic expression of p63 was also observed in the normal adult thymus
      tissue, especially in the subcapsular region. An increased number of p63-
      positive cells in the thymus after irradiation indicates that repair or renewal
      of the thymic epithelial cells may be taking place because p63 is more specific
      to transient amplifying thymic epithelial cells. A RT-PCR analysis of p63
      expression in irradiated and regenerating thymus tissue also showed an increased
      expression of p63 after irradiation compared with that of the normal thymus.
      These results suggest that changes in the thymic microenvironment-especially in
      relation to the repair and renewal of thymic epithelial cells- may have an
      important influence on thymocyte proliferation in the normal thymus as well as in
      the irradiated and recovering thymus.

PMID- 15468955
TI  - Cytoarchitecture of the normal rat olfactory epithelium: light and scanning
      electron microscopic studies.
AB  - The three-dimensional cytoarchitecture of the normal rat olfactory epithelium was
      examined by scanning electron microscopy (SEM) of KOH digested tissues as well as
      by light and transmission electron microscopy of plastic sections. Observations
      specimens from the lateral side of the olfactory epithelium allowed
      identification of four cell types by their surface structure: olfactory neurons,
      supporting cells, basal cells, and duct cells of the Bowman's gland. The
      olfactory neurons were characterized by the presence of a thick apical process
      (i.e., dendrite) and a thin basal process (i.e., axon). These olfactory neurons
      tended to be aligned along the vertical axis of the epithelium. Immature
      olfactory neurons were present at the basal part of the epithelium and had a pear
      shaped cell body with a thin and long axon and a short dendrite which failed to
      reach the epithelial surface. Supporting cells were roughly columnar in shape and
      occupied the full length of the epithelium. They became thinner in the basal two
      thirds of their length but had branched foot processes spreading on the basal
      surface of the epithelium. Basal cells located in the basal epithelial region
      were oval, round or cuboidal and present among the foot processes of the
      supporting cells. The ducts of the Bowman's gland entered the epithelium from the
      lamina propria and took straight, perpendicular courses within the epithelium.
      These intraepithelial ducts were composed of several slender cells. The acinar
      cells are sometimes present in the epithelium and appeared as a globular bulge of
      the duct at the basal part of the epithelium. SEM observation of the basal
      surface of the olfactory epithelium also clearly showed that axon bundles were
      surrounded by the sheet-like processes of Schwann cells, the investment being
      found at the base of the epithelium just before axon bundles leave the
      epithelium.

PMID- 15468956
TI  - Atomic force microscopy of human metaphase chromosomes after differential
      staining of sister chromatids.
AB  - Human metaphase chromosomes, in which 5-bromo-deoxyuridine (BrdU) had been
      incorporated into the DNA, were treated with the fluorescent plus Giemsa (FPG)
      method. Use of this method distinctly stained one of the paired sister chromatids
      with the Giemsa solution due to the difference in content of BrdU in the two
      chromatids. These chromosomes with their differential staining of sister
      chromatids were observed by atomic force microscopy (AFM). In the air-dried
      specimens, one of the paired chromatids that was stained strongly with Giemsa
      solution was about two times higher than the counterpart that was stained faintly
      with Giemsa solution. In the critical point dried chromosomes, the height of the
      Giemsa positive chromatid roughly matched that of the Giemsa negative
      counterpart. These findings imply that the arrangement of the Giemsa negative
      chromatid after FPG staining is fragile and easily collapses due to the surface
      tension of water during air-drying. At higher magnifications, the surface
      structure differed between Giemsa positive and negative chromatids; the Giemsa
      positive chromatid (i.e., unifilarly BrdU-incorporated chromatid) was composed of
      fibrous structures while the Giemsa negative chromatid (i.e., bifilarly BrdU
      incorporated chromatid) exhibited a fine granular appearance. These structural
      changes in the sister chromatids are thought to arise from the ultraviolet
      irradiation and heating of the chromosomes during FPG staining.

PMID- 15468957
TI  - Mitochondria-filled nerve endings around the terminal arteriole in the rat
      posterior cricoarytenoid muscle.
AB  - We employed light and electron microscopy to examine the innervation of terminal
      arterioles in the rat posterior cricoarytenoid (PCA) muscle over a three-week
      period before and after unilateral denervation of the recurrent nerve.
      Observations showed an occasional single small-sized myelinated nerve fiber
      around the terminal arteriole in both normal and denervated PCA muscles. One axon
      after the last node of Ranvier of the small-sized myelinated nerve fiber,
      together with some nonmyelinated nerve fibers, was enwrapped by the Schwann cell
      and ran along the terminal arteriole, forming varicose swellings with numerous
      mitochondria along its course. In one instance, a small-sized myelinated nerve
      fiber in the denervated PCA muscle ramified into several branches containing
      numerous mitochondria. These nerve endings mainly existed in the adventitia,
      consisting of some layers of fibroblasts and collagen fibrils, and some of them
      were close to the vascular smooth muscle cells with only an intervening basal
      lamina. These findings suggest that the mitochondria-filled nerve endings may be
      sensory in nature, and function in response to the expansion and contraction of
      blood vessels caused by increased and/or decreased blood flow or intravascular
      pressure.

PMID- 15468958
TI  - REM sleep is impaired by a small amount of alcohol in young women sensitive to
      alcohol.

PMID- 15468959
TI  - Ambulatory motor activity monitoring of Parkinson disease.

PMID- 15468960
TI  - Recurrent ADEM or MS?

PMID- 15468961
TI  - Molecular biology of erythropoietin.
AB  - The glycoprotein hormone erythropoietin (EPO) is an essential viability and
      growth factor for the erythrocytic progenitors. EPO is mainly produced in the
      kidneys. EPO gene expression is induced by hypoxia-inducible transcription
      factors (HIF). The principal representative of the HIF-family (HIF-1, -2 and -3)
      is HIF-1, which is composed of an O2-labile alpha-subunit and a constant nuclear
      beta-subunit. In normoxia, the alpha-subunit of HIF is inactivated following
      prolyl- and asparaginyl-hydroxylation by means of alpha-oxoglutarate and Fe(2+)
      dependent HIF specific dioxygenases. While HIF-1 and HIF-2 activate the EPO gene,
      HIF-3, GATA-2 and NFkappaB are likely inhibitors of EPO gene transcription. EPO
      signalling involves tyrosine phosphorylation of the homodimeric EPO receptor and
      subsequent activation of intracellular antiapoptotic proteins, kinases and
      transcription factors. Lack of EPO leads to anemia. Treatment with recombinant
      human EPO (rHuEPO) is efficient and safe in improving the management of the
      anemia associated with chronic renal failure. RHuEPO analogues with prolonged
      survival in circulation have been developed. Whether the recent demonstration of
      EPO receptors in various non-hemopoietic tissues, including tumor cells, is
      welcome or ominous still needs to be clarified. Evidence suggests that rHuEPO may
      be a useful neuroprotective agent.

PMID- 15468962
TI  - Circulating endothelial cells and vasculitis.
AB  - Systemic vasculitides are a heterogeneous group of disorders with inflammation of
      blood vessels as their common pathogenetic hallmark. They often pose difficulties
      with regard to diagnosis and monitoring of disease activity, both at the initial
      presentation and during follow-up. Novel markers of disease activity are
      therefore eagerly awaited. Circulating endothelial cells have recently emerged as
      one such marker and we have demonstrated their clinical use in ANCA-associated
      small-vessel vasculitis. Not only entire cells but also endothelial
      microparticles can be detected in vasculitis although their use is not
      established to date. Repair of endothelial damage is believed to occur via
      endothelial progenitor cells and their precise role in vasculitis is also unclear
      at present. Circulating endothelial cells may complement, rather than replace,
      conventional markers of disease activity. The ultimate aim of our studies may
      thus be a panel of various laboratory markers for systemic vasculitis.

PMID- 15468963
TI  - Favorable outcome of low-dose cyclosporine after pulse methylprednisolone in
      Japanese adult minimal-change nephrotic syndrome.
AB  - OBJECTIVE: There have been few studies on cyclosporine (CsA) monotherapy in adult
      minimal change nephrotic syndrome (MCNS). To delineate CsA therapy as new
      treatment options for MCNS, we conducted a prospective single-center study.
      METHODS: We assessed the efficacy of 3 different regimens in 36 patients,
      consisting of 26 first attacks or 10 relapses, of adult-onset MCNS. In 12
      patients, CsA alone was given orally at a dose of 2-3 mg/kg/d, and in 12
      patients, CsA after intravenous pulse methylprednisolone therapy (CsA/PMT) was
      given at the same dose. CsA was given for 12 months, tapered slowly, then
      stopped. The other 12 patients were treated with oral prednisolone (PSL, 40-60
      mg/d) alone for 4 to 6 weeks, followed by daily PSL, with slowly tapering doses.
      RESULTS: Complete remission (CR) was obtained in 75% with CsA alone, 100% with
      CsA/PMT and 92% with PSL alone (p = 0.0379). The days required for CR were
      shortest in the CsA/PMT group (40.9 +/- 35.5 days with CsA alone vs. 11.0 +/- 5.6
      with CsA/PMT vs. 21.5 +/- 15.8 with PSL alone). The cumulative rates of CR were
      significantly different among the 3 groups (p < 0.0001). The real numbers of the
      relapse were smallest in the CsA/PMT group, however, the cumulative rates of
      sustained remission among the 3 treatment arms were not statistically different.
      Renal function was well preserved with each treatment period. CsA-associated
      adverse effects were minimal but one patient developed new-onset hypertension and
      gingival hyperplasia. However, the adverse effects of PSL alone were serious in 3
      cases: bleeding from gastric ulcer, diabetes mellitus, and aseptic necrosis. Many
      patients with PSL but few with CsA experienced cosmetic problems. CONCLUSIONS:
      CsA/PMT may be the most advantageous when the clinical efficacy of each treatment
      for MCNS is integrated.

PMID- 15468964
TI  - Influence of inhaled corticosteroids on community-acquired pneumonia in patients
      with bronchial asthma.
AB  - OBJECTIVE: The aim of the present study was to evaluate the influence of inhaled
      corticosteroids (ICS) on community-acquired pneumonia (CAP) in patients with
      asthma. PATIENTS AND METHODS: All asthmatic patients who required hospitalization
      for CAP from the beginning of 1989 through December 2001 were enrolled in this
      retrospective study. Patients who used oral corticosteroids daily were excluded.
      Patients were divided into two groups based on whether or not they used ICS, and
      we analyzed clinical characteristics of the pneumonia. Sixty-two patients (28
      males, 34 females; mean age, 54.5 years) were enrolled in this study. Thirty
      seven of 62 patients used ICS, with the mean dosage being 777.9 microg/day.
      RESULTS: We found no significant differences between the two groups with regard
      to mean age, serum albumin level, duration of asthma, pulmonary function and
      frequency of intravenous infusion of corticosteroids in the outpatient
      department. There were no significant differences in body temperature, white
      blood cell count, and CRP value upon admission between the two groups.
      Differences were not significant in the period of resolution of the pneumonia or
      in the frequency of pathogens identified between the two groups. CONCLUSION: ICS
      therapy appears to have no influence on CAP in patients with asthma. We recommend
      that ICS should be continued to control asthma with adequate antibiotic therapy
      when asthmatic patients have CAP.

PMID- 15468965
TI  - REM sleep is impaired by a small amount of alcohol in young women sensitive to
      alcohol.
AB  - OBJECTIVE: The effect of a small amount of alcohol on the sleep structure in
      relation to alcohol sensitivity was examined using polysomnography (PSG).
      METHODS: Alcohol sensitivity was evaluated using alcohol patch test for all
      subjects. PSGs were performed on three nights after one night for acclimation,
      and subjects consumed no alcohol, 0.28 or 0.69 g ethanol/kg body weight,
      respectively, before going to bed. The percentages of sleep time in each sleep
      stage of 1, 2, 3+4 and rapid eye movement (REM), REM latency, and REM cycle were
      calculated. SUBJECTS: Thirteen healthy female students (age 21.1 +/- 0.7 years)
      were enrolled in this study. RESULTS: In all subjects, there were no significant
      differences in any of the sleep parameters between baseline night and alcohol
      nights. Six of the 13 subjects were sensitive to alcohol, in whom %stage REM was
      significantly decreased by alcohol consumption (baseline night: 18.3 +/- 6.2%,
      alcohol night I: 9.8 +/- 5.1% and alcohol night II: 11.0 +/- 2.8%), and the REM
      latency was significantly prolonged. The standard deviation of REM cycle was
      significantly greater on alcohol nights I and II than baseline night. There were
      no significant differences in other sleep parameters. In the other seven subjects
      who were insensitive to alcohol, none of the sleep parameters were significantly
      affected by alcohol consumption. CONCLUSION: REM sleep was adversely affected by
      a small amount of alcohol in alcohol-sensitive healthy young women. Alcohol
      sensitivity might play some important role in impaired REM sleep by an ingestion
      of a small amount of alcohol.

PMID- 15468966
TI  - Lifecorder: a new device for the long-term monitoring of motor activities for
      Parkinson's disease.
AB  - OBJECTIVE: To quantitatively evaluate motor activity, its fluctuations, and drug
      effects in patients with Parkinson's disease (PD), the Lifecorder, a new
      monitoring device, was attached to a group of patients for several weeks. This
      enabled the continuous recording of motor activity in ten scaled magnitudes at
      two-minute intervals for 6 weeks. PATIENTS AND METHODS: Thirteen patients with PD
      who required dopamine receptor agonist therapy were monitored with Lifecorder,
      and seven healthy subjects served as the control group. The data obtained with
      this device correlated well with the Unified Parkinson's Disease Rating Scale
      (UPDRS) and Hoehn-Yahr grading. The dose of cabergoline, a D2-receptor agonist,
      was increased every 2 weeks, until optimum improvement was achieved. RESULTS: By
      adding cabergoline, the mean UPDRS improved from 40.5 to 28.4, which was
      significant. In parallel, the mean daily walking count (WC) also increased from
      2,459 to 3,315 steps (p < 0.01) and movement-related calorie consumption (MCC)
      increased from 56 to 74 kcal (p < 0.05). UPDRS thus correlated well with WC and
      MCC (p < 0.05) obtained with this device. The improvement ratio of WC and MCC of
      each individual patient was compared with that of UPDRS. WC, and MCC shifted in
      parallel with UPDRS with one exception. The daily time-dependent fluctuation of
      motor activity was clearly shown by the Excel-generated graphs to improve with D
      agonist therapy. In contrast to enhanced daytime activities, nocturnal
      restfulness was also clearly documented with this device. CONCLUSION: The unique
      properties of Lifecorder make this device a useful adjunct to the UPDRS for the
      objective evaluation of Parkinsonian motor activity. The device has a significant
      advantage over conventional clinical scales, as daytime as well as nocturnal
      motor activity can be objectively evaluated over long time periods ranging from
      one hour to one month, and the magnitude of motor activity is quantifiable in
      relation to the time-course.

PMID- 15468967
TI  - Onset of ischemic colitis following use of electrical muscle stimulation (EMS)
      exercise equipment.
AB  - Our patient was a 71-year-old man who presented with lower abdominal pain, and
      bloody and white mucosal stools. He purchased by mail-order an electrical muscle
      stimulation (EMS) device, which he strapped onto his lower abdomen, and for 2
      consecutive days he underwent muscle stimulation comprising 600 contractions at
      2.40 mA and 1.20 V over a 10 minute period. He experienced the onset of lower
      abdominal pain immediately following muscle stimulation on the second day, and
      then passed stools containing blood and white mucus. The cause was thought to be
      electrical and mechanical stimulation of the lower abdomen by the EMS equipment,
      either inducing colonic or vascular spasm, or dislodging thrombi associated with
      atrial fibrillation or atherosclerosis. This is the first known report of
      ischemic colitis associated with the use of EMS exercise equipment. We report
      this case in the belief that this condition is likely to become more common with
      increasing use of such devices.

PMID- 15468968
TI  - Gianotti-Crosti syndrome caused by acute hepatitis B virus genotype D infection.
AB  - A 12-year-old girl with Gianotti-Crosti syndrome caused by hepatitis B virus
      (HBV) infection was admitted due to eruption on her extremities. Laboratory
      findings revealed elevation of transaminase, positivity for HB surface antigen
      (HBsAg), and an IgM type anti-HB core. The eruption and level of transaminase
      improved, and HBsAg became negative within 2 months of onset. Analysis of the
      virus revealed it to be genotype D with a genomic length of 3,182 bases and the
      HBsAg serotype was ayw3, which is very rare in Japan. The possible relationship
      between Gianotti-Crosti syndrome and HBV genotype D infection is discussed.

PMID- 15468970
TI  - Large duodenal somatostatinoma in the third portion associated with severe
      glucose intolerance.
AB  - A 51-year-old man was admitted with hyperglycemia and a duodenal tumor. Although
      his glycemic control was poor, basal C-peptide levels were not suppressed.
      Further examination revealed a mass measuring 7.8 cm in diameter in the third
      portion of the duodenum. Duodenectomy revealed a slow-growing sessile tumor
      located near Treitz's ligament. The immunohistochemical profile of sections of
      the specimen revealed the presence of somatostatin. The patient's serum
      somatostatin was elevated to 300 pg/ml preoperatively, but was reduced to 10
      pg/ml postoperatively. Glycemic control also normalized after the operation.

PMID- 15468969
TI  - Cardiomyopathy with prominent autophagic degeneration, accompanied by an elevated
      plasma brain natriuretic peptide level despite the lack of overt heart failure.
AB  - A 75-year-old man without overt heart failure showed an abnormally high level of
      brain natriuretic peptide (BNP) in plasma: 600 pg/ml. The left ventricular
      endomyocardial biopsy revealed prominent vacuolar degeneration in the myocytes,
      most of which were positive for PAS stain and BNP immunoreaction.
      Ultrastructurally, degenerative changes of myocytes were marked, such as deposits
      of glycogen and lipofuscin granules in the cytoplasm, but the most prominent
      finding was giant vacuoles containing degraded mitochondria, glycogen granules,
      myofibrils, and myelin-like structures (autophagosomes). This case may belong to
      one of the unclassified cardiomyopathies characterized by prominent autophagic
      vacuoles.

PMID- 15468971
TI  - Worsening fluid retention in a patient with hereditary angioedema and end-stage
      renal disease.
AB  - A 60-year-old woman who was diagnosed with hereditary angioedema (HAE) developed
      nephrotic syndrome, with end-stage renal disease (ESRD) occurring about 2.5 years
      later. During her slide toward ESRD, she experienced three severe episodes of
      angioedema that each resulted in significant fluid retention. Though the
      therapeutic administration of C1-inhibitor concentrate was effective in
      controlling her angioedema, seemed ineffective in preventing her from developing
      ESRD requiring hemodialysis treatment. We theorized that the patient's low
      colloid osmolality and glomerular perfusion were important facilitators of her
      attacks of angioedema.

PMID- 15468972
TI  - Pulmonary Langerhans cell histiocytosis associated with lingual carcinoma.
AB  - A 57-year-old man who was a heavy smoker was admitted to our hospital for further
      evaluation of abnormal shadows on a chest X-ray film. Chest radiography and a
      computed tomography (CT) scan revealed nodular lesions and multiple thin-walled
      cysts in both lungs. Histopathological examination of one of these cystic lesions
      showed that the predominant cellular population was Langerhans cells, with the
      cytoplasm testing positive for S-100 protein and the cell membrane showing a
      positive reaction for CD1a. The pathological diagnosis was pulmonary Langerhans
      cell histiocytosis (LCH). A lingual carcinoma that had been detected
      simultaneously was treated with neoadjuvant therapy and the patient was advised
      to stop smoking. However, only limited improvement was seen on follow-up chest
      CT. In view of this, a radical resection of the lingual carcinoma was performed.
      There was a subsequent dramatic improvement in the pulmonary LCH. Langerhans
      cells may play a role in the immune response to tumors. In this patient, we
      suggest the possibility that both the habitual smoking and the lingual carcinoma
      may have contributed to the development of pulmonary LCH.

PMID- 15468973
TI  - Gefitinib as a first line of therapy in non-small cell lung cancer with brain
      metastases.
AB  - Two Japanese women were diagnosed as having well-differentiated adenocarcinoma of
      the lung with brain metastases. Since it was considered they could not tolerate
      conventional chemotherapy, we administered gefitinib without any previous
      systemic therapy. In both patients gefitinib acted dramatically on all the
      lesions including the brain metastases, resulting in a marked decrease of the
      elevated CEA levels, and improvement of their quality of life. Retrospective
      evaluation of epidermal growth factor receptor expression levels by
      immunohistochemistry revealed positive results in both cases. Though gefitinib
      has been recommended for patients previously treated with chemotherapy, it should
      be considered feasible as a first line therapy.

PMID- 15468974
TI  - Three cases of non-specific interstitial pneumonia associated with primary lung
      cancer.
AB  - NSIP associated with primary lung cancer has been rarely reported. In the present
      report, three cases of histologically proven non-specific interstitial pneumonia
      (NSIP) associated with primary lung cancer are described. Importantly, in our 3
      cases, interstitial pneumonia which is histologically proven to be NSIP was
      observed diffusely in both lungs. NSIP in these 3 cases responded to steroid
      therapy. However, 2 patients died from primary lung cancer and 1 patient died
      from progression of the interstitial pneumonia. Although the association between
      lung cancer and NSIP has been rarely documented, this combination was considered
      to be one of the paraneoplastic phenomena. The possible association between
      primary lung cancer and NSIP is discussed.

PMID- 15468975
TI  - Tongue metastasis as an initial presentation of a lung cancer.
AB  - Metastasis to the tongue seldom occurs, and lingual metastasis as an initial sign
      of cancer occurs even less frequently. We report a case of lung cancer in which
      the patient's initial symptom was related to the tongue metastasis. A 63-year-old
      man had a submucosal tumor on the left posterolateral aspect of the tongue and a
      biopsy specimen of the tongue tumor showed poorly differentiated squamous cell
      carcinoma. A chest X-ray showed a mass in the right lung and cytological
      examination of the specimen obtained by bronchial brushing showed poorly
      differentiated squamous cell carcinoma, whose appearance was similar to that of
      the tongue. Based on these findings, the tongue lesion was diagnosed a metastatic
      tumor from the lung cancer. The patient received radiation therapy combined with
      systemic chemotherapy, however, he died 5 months after the diagnosis of lung
      cancer. An autopsy revealed a lung cancer in the right lower lobe with metastatic
      tumors in the tongue, right middle lobe, left upper lobe, liver, adrenal gland,
      pericardium, heart, and subcutaneous tissues. No other possible primary cancer
      that may have been the cause of the metastases was identified.

PMID- 15468976
TI  - Pulmonary strongyloidiasis in a patient receiving prednisolone therapy.
AB  - Strongyloidiasis is widely distributed in tropical and subtropical areas.
      Disseminated strongyloidiasis may develop in patients with immunodeficiencies. In
      the absence of early diagnosis and treatment, the prognosis of disseminated
      strongyloidiasis is extremely poor. We report a case of pulmonary
      strongyloidiasis that was successfully treated. The patient was an 83-year-old
      woman who had been receiving long-term oral prednisolone therapy for uveitis. The
      patient visited our emergency department complaining of breathing difficulties
      and diarrhea. A chest X-ray revealed a diffuse enhancement of interstitial
      shadows. A bronchoalveolar lavage (BAL) was performed, and both Gram staining and
      Grocott's staining revealed the presence of multiple filariform larvae of
      Strongyloides stercoralis in the bronchoalveolar lavage fluid (BALF). A stool
      examination performed at the same time also yielded S. stercoralis. The patient
      was diagnosed as having pulmonary strongyloidiasis and was treated with
      thiabendazole and ivermectin, in addition to antimicrobial agents; her
      respiratory symptoms and diarrhea improved, and S. stercoralis was not detected
      in subsequent follow-up examinations thereafter. In endemic areas of S.
      stercoralis, pulmonary strongyloidiasis should be considered as part of a
      differential diagnosis if chest imaging findings like alveolar and interstitial
      shadow patterns or lobar pneumonia are seen in patients with immunodeficiencies.

PMID- 15468977
TI  - Successful treatment of hypersensitivity pneumonitis caused by Grifola frondosa
      (Maitake) mushroom using a HFA-BDP extra-fine aerosol.
AB  - We successfully treated a patient with occupational hypersensitivity pneumonitis
      (HP) caused by Grifola frondosa (Maitake) mushroom spore with an extra-fine
      aerosol corticosteroid; beclomethasone dipropionate (BDP) dissolved in
      hydrofluoroalkane-134a (HFA). A 49-year-old woman developed respiratory symptoms
      3 months after beginning work on a mushroom farm. She was diagnosed as HP based
      on radiological and serological findings. Oral prednisolone therapy improved her
      HP and she returned to the same farm. Her HP relapsed after 5 months, and daily
      400 microg of HFA-BDP was administered with gradual improvement. An extra-fine
      particle inhaled corticosteroid might reach appropriate alveoli to be effective
      therapy for mild HP.

PMID- 15468978
TI  - Sinus histiocytosis with massive lymphadenopathy associated with malignant
      lymphoma.
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML) is a distinct benign
      clinicopathological entity, characterized by painless enlargement of lymph nodes
      due to sinus histiocytosis. Here, we report a case of SHML with diffuse large B
      cell lymphoma. A 64-year-old man was admitted to our hospital because of fever.
      He presented with enlargement of a small cervical lymph node and huge abdominal
      paraaortic lymphadenopathy. Cervical lymph node biopsy revealed SHML and bone
      marrow biopsy showed infiltration of large B-cell lymphoma. Several cases of SHML
      associated with lymphoma have been documented to date, but this type of
      simultaneous occurrence has not yet been reported.

PMID- 15468979
TI  - Recurrence of acute disseminated encephalomyelitis after a 12-year symptom-free
      interval.
AB  - We report a patient with recurrent acute meningoencephalitis who had three
      episodes of headache, fever and unconsciousness; the first episode was at age 6
      and the second, at age 7. After a 12-year symptom-free interval, she had a
      relapse, exhibiting the same symptoms as those in the previous two episodes. Head
      magnetic resonance imaging also revealed the recurrence of lesions in the basal
      ganglia and medial portion of the temporal lobe. The occurrences of stereotyped
      symptoms with meningoencephalitis and the same lesions in the basal ganglia
      observed in each episode favor the diagnosis of recurrent acute disseminated
      encephalomyelitis (ADEM) rather than multiple sclerosis or multiphasic
      disseminated encephalomyelitis. The occurrence of this rare case suggests that
      ADEM can relapse after a very long symptom-free interval.

PMID- 15468980
TI  - Methanol intoxication: differential diagnosis from anion gap-increased acidosis.
AB  - We report a case of methanol intoxication, which was not distinguished from
      ethylene glycol intoxication during treatment. A 65-year-old man was transferred
      to our emergency department because of drowsiness and remarkable metabolic
      acidosis. He was intubated because his consciousness disturbance worsened. The
      diagnosis was suspected as methanol or ethylene glycol intoxication in addition
      to ethanol intoxication. Administration of ethanol and hemodialysis were chosen
      for his essential treatments. When he was extubated, he complained about visual
      loss. His brain computed tomography scans revealed putaminal lesions, which are
      rarely reported in methanol intoxication. Diagnosis of methanol intoxication was
      confirmed by the serum high methanol levels.

PMID- 15468981
TI  - Acute respiratory failure with gross hemoptysis in a patient with
      lymphangioleiomyomatosis as part of tuberous sclerosis complex.
AB  - A 29-year-old woman was admitted to our hospital with a 7-day history of elevated
      temperature to 39.5 degrees C associated with headache and nausea. She had been
      diagnosed with tuberous sclerosis complex 10 years earlier. Her unconsciousness
      progressed, and she was diagnosed as having aseptic meningoencephalitis. The next
      day, she had a generalized seizure with severe hemoptysis, and she suddenly fell
      into severe respiratory failure (PaO2/FiO2 = 76.9). Transbronchial lung biopsy
      revealed the findings of lymphangioleiomyomatosis. It was suggested that
      neurogenic pulmonary edema accompanied with venous flow obstruction by
      lymphangioleiomyomatosis lesions resulted in diffuse pulmonary hemorrhage with
      resultant gross hemoptysis accelerating to severe hypoxemia.

PMID- 15468982
TI  - Spontaneous rupture of the lumbar artery.

PMID- 15468983
TI  - Changes in lipoprotein profile after selective LDL apheresis.

PMID- 15468984
TI  - Emphysematous cystitis.

PMID- 15468985
TI  - "Honeycomb lung" in an HTLV-I carrier.

PMID- 15468986
TI  - Adenocarcinomatosis of the bone marrow and secondary acute myeloid leukemia.

PMID- 15468987
TI  - Circulating macroglobulinemia cells.

PMID- 15468988
TI  - Iron deficiency anemia due to repeated blood donations.

PMID- 15468989
TI  - Comorbidity in Alaska: evidence and implications for treatment and public policy.

PMID- 15468990
TI  - Comparison of BMI and body fat determinations in rural Alaska women: results of
      the WIC Healthy Mom Survey, Summer 2001.
AB  - OBJECTIVES: Evaluate two field methods to assess body composition of rural Alaska
      women. Excess body fat has been correlated with chronic diseases. METHODS: This
      exploratory study used an orally administered survey of a self-selected sample
      from five rural Alaskan villages. Electrical impedance technique was used to
      determine percent of body fat. Body Mass Index (BMI) was calculated based on
      clinically obtained height and weight and compared to historical data by
      geographical regions. Self-reported health data and fingerstick screenings were
      used to assess health status. RESULTS: The body mass index tool assessed more
      women at excessive weight than did the percent body fat assessment tool.
      Fingerstick screenings for glucose, cholesterol, and hemoglobin were generally
      found to be in normal ranges. CONCLUSIONS: Percent of body fat may be more
      accurate to determine weight status for many Alaska Native women. Historical body
      mass indices may indicate periods of prolonged limited food supplies for a
      geographic region.

PMID- 15468991
TI  - Improvement of vestibular compensation by Levo-sulpiride in acute unilateral
      labyrinthine dysfunction.
AB  - L-sulpiride is the levorotatory enantiomer of sulpiride, a neuroleptic of the
      family of benzamide derivatives; it has a characteristic antagonist effect on
      central DA2 dopaminergic receptors and dopamine DA1 "autoreceptors". Its efficacy
      in the symptomatic control of acute vertigo spells has been recognized, apart
      from its well-known antiemetic, antidyspeptic and anti-depressant properties, at
      high dosages. To establish objective parameters of the results of its clinical
      application, a randomized prospective study was started comparing the effects of
      the drug in a group of 87 patients with vertigo of peripheral origin, with those
      in a control group treated with other vestibular suppressants. The drug was
      administered via the intravenous route, 25 mg t.i.d., for the first 3 days, then
      by oral administration, with the same schedule and dosage, for a further 7 days.
      After clinical evaluation of vestibular signs and symptoms,
      electronystagmographic recordings of rotatory tests were obtained, at admission
      and were then controlled after 6 months. A subjective Visual Analogue Scale was
      also delivered daily to the patients in order to monitor symptomatic
      improvements. When compared to conventional treatments, L-sulpiride appeared to
      induce a statistically significant faster recovery in unilateral vestibular
      lesions. An unexpected favourable outcome of treatment was the facilitation of
      spontaneous vestibular compensation, in terms of lesser residual labyrinthine
      dysfunction and reduction of recurrent vertigo attacks during the 6 months follow
      up. The mechanisms of action of the drug and its interaction with the vestibular
      system are discussed.

PMID- 15468992
TI  - Test-retest reliability of the VOR as measured via Vorteq in healthy subjects.
AB  - To determine the reliability of the vestibolo-ocular reflex test measured via
      Vorteq, 16 subjects underwent head-autorotation test at the frequencies 1-5 Hz.
      All patients underwent the re-test. No linear correlation was observed between
      the measurements, i.e., no repeatability of the same measurements at the various
      frequencies. The Head Auto-Rotation Test by Vorteq has demonstrated advantages:
      patients are not disturbed by the active head movements; the full test protocol,
      lasts only a few minutes; the method enables the vestibolo-ocular reflex to be
      evaluated at high head-rotation frequencies. However, the test has disadvantages:
      poor test-retest inter-individual repeatability, wide standard deviations of
      results with heterogeneous inter-individual spread with regard to phase and
      asymmetry values especially at high rotation frequencies. In the light of the
      above findings, it can be seen that the test-retest of the Vorteq system is not
      sufficiently reliable and hence cannot be used in clinical practice.

PMID- 15468993
TI  - Rhinopharynx endoscopy in the diagnosis of chronic otitis media with effusion in
      infancy.
AB  - Chronic otitis media with effusion is an inflammatory process of the mucosa of
      the middle ear persisting for more than 3 months, being most frequent in infancy,
      and is correlated with marked tube obstruction. In infancy, the most frequent
      cause of this obstruction is adenoid hypertrophy and diagnosis, clinical or
      radiological, is often not confirmed by rhinopharynx fiberendoscopy. Since, in
      these cases, treatment is often surgical, it is possible that small patients may
      be submitted, unnecessarily, to adenoidectomy. In collaboration with the
      Paediatric Clinic, the present study on an infant outpatient population with
      nasal respiratory difficulty, associated with chronic otitis media with effusion,
      was, therefore, aimed at standardizing the endoscopic diagnosis of patients with
      suspected adenoid hypertrophy. Between October and December 2002, 32 consecutive
      patients, aged between 4 and 11 years, all oral breathers with OME, were sent to
      our attention from the Paediatric Clinic. All those patients, with indication for
      adenoidectomy, have been enrolled in the study and submitted to fiberendoscopic
      examination of the external ear and nose. Nasal respiration was confirmed with
      active anterior rhinomanometry. Endoscopic evaluation of the rhinopharynx, aimed
      at assessing adenoid dimensions and their relationship with the auditory tube,
      has been expressed in four degrees of increasing severity and adenoidectomy was
      indicated in those cases, classified, by us, as third and fourth degree. In our
      experience, endoscopic examination of the rhinopharynx has, however, shown that
      only 9 children (28.2%) presented an absolute need to undergo adenoidectomy since
      they were carriers of massive adenoid hypertrophy with tubal obstruction and
      consequent bilateral glue ear (3rd and 4th degree) while, in all other cases
      (71.8%), the clinical and radiological findings did not correspond to endoscopic
      data. Diagnostic accuracy that characterizes rhinopharyngeal fiberendoscopy is,
      therefore, in our opinion, of fundamental importance to avoid these errors, as
      far as possible, and in establishing an appropriate therapeutic programme.

PMID- 15468994
TI  - Role of skin-lined tracheotomy in obstructive sleep apnoea syndrome: personal
      experience.
AB  - Permanent tracheotomy was the first surgical procedure proposed for the treatment
      of severe obstructive sleep apnoea syndrome and is still the only surgical option
      that ensures, even in very severe cases, complete elimination of apnoea and, in
      turn, clinical remission. Improved knowledge of the causes of obstructive sleep
      apnoea syndromes and the increasing therapeutic options (instrumental, medical
      and surgical) have resulted in cases requiring tracheotomy as the only
      indispensable therapeutic option becoming more rare. At present, the only
      indications are in very occasional conditions of life-threatening obstructive
      sleep apnoea syndromes and in patients on whom continuous positive airway
      pressure is not tolerated or is not effective (severe deoxygenation or
      hypercapnia, severe respiratory disorder index, severe obstructive sleep apnoea
      syndrome-related arrhythmias, severe excessive daytime sleepiness, heart diseases
      or ischaemic encephalopathy exacerbated by obstructive sleep apnoea syndromes,
      obstructive pneumopathy exacerbated by obstructive sleep apnoea syndromes, severe
      obstructive sleep apnoea syndromes with few chances of resolution with other
      surgical procedures or failure of the latter). Moreover, it is the only
      therapeutic solution in rare nocturnal laryngeal stridor due to multisystemic
      atrophy (in which obstructive sleep apnoea syndrome is due to nocturnal
      laryngospasm of neurologic origin). Therapeutic tracheotomy must be permanent
      (tracheostomy) and, therefore, preferably carried out with a specific technique
      (skin-lined tracheotomy), able to guarantee greater stability, less risk of
      granulation tissue, wider opening of the tracheostomy, sufficient reversibility.
      In our experience, very few patients (10 cases) withsleep disorder breathing have
      been submitted to skin-lined tracheotomy. Of these, the majority were submitted
      to surgery for severe apnoea due to nocturnal laryngospasm on account of
      multisystemic atrophy (n = 7), while only 3 cases of obstructive sleep apnoea
      syndromes were submitted to skin-lined tracheotomy, i.e., 0.7% of the 424
      patients operated on for obstructive sleep apnoea syndrome and 1.7% of the 175
      operated on for severe, or very severe, obstructive sleep apnoea syndromes (RDI >
      40). Skin-lined tracheotomy was not followed by important complications and
      expected results were achieved with immediate disappearance of daytime symptoms
      and considerable improvement in nocturnal apnoea. Besides sleep-related
      disorders, numerous clinical situations with indications for a permanent
      tracheotomy may benefit from the skinlined technique, such as severe laryngeal or
      tracheal stenoses, laryngeal diplegias, miasthenia gravis, lateral amyotrophic
      sclerosis, intractable aspiration, severe emphysema.

PMID- 15468995
TI  - Closure of tracheo-oesophageal fistula following removal of voice prosthesis; a
      new surgical technique.
AB  - The voice prosthesis is today the most widely used and accepted method of voice
      restoration following total laryngectomy. Fortunately, the cases in which it is
      necessary to temporarily or definitively close the fistula are rare (request of
      the patient, leakage from the fistula, aspiration pneumonia). Herein, an analysis
      is made of these cases and the surgical technique personally developed for the
      closure of tracheo-oesophageal fistula is described. This technique has been used
      in 8 patients with good results; moreover, it is a relatively low cost procedure
      and gives rise to few post-operative complications.

PMID- 15468996
TI  - Internal auditory canal metastasis.
AB  - This report deals with 3 cases of internal auditory canal metastasis, an
      extremely rare lesion, few cases having been reported in the international
      literature. Since pre-operative diagnosis is fundamental in the planning of a
      correct therapeutic strategy, it is important that the neurotologist be aware of
      the possibility of their occurrence in this particular area. Metastasis can occur
      unilaterally as well as bilaterally; the latter being the case in 1 of the
      patients described herein. Correct pre-operative diagnosis is particularly
      difficult in patients in whom the primary tumour has not been detected at the
      time of identification of the lesion in the internal auditory canal. The only
      characteristic, specific of metastasis, is the presence of multifocal cerebral
      lesions. However, these were detected in only 1 of the present cases. On the
      contrary, in cases of a single metastasis, both magnetic resonance imaging and
      computed tomography usually fail to show any distinctive feature when compared to
      the most common tumours of the internal auditory canal (vestibular schwannomas
      and meningiomas). Bilateral metastases can also be misdiagnosed as
      neurofibromatosis type 2. Clinical data that should alert the clinician are:
      rapidly progressive sensorineural hearing loss, followed by onset of progressive
      facial nerve weakness. Radiotherapy and/or chemotherapy are the two main
      treatment modalities, while surgical removal is reserved for selected cases of a
      single metastasis. Albeit, due to the paucity of specific radiological and
      clinical characteristics, surgical removal is often necessary to reach the
      correct diagnosis, as occurred in 2 of the present patients.

PMID- 15468998
TI  - Breast carcinoma metastases in paranasal sinuses, a rare occurrence mimicking a
      primary nasal malignancy. case report.
AB  - Metastatic tumours to the paranasal sinuses are an exceedingly rare event, the
      large majority being of renal origin. Herein, a case of metastatic breast
      carcinoma to the right maxilla is described which occurred 4 years after radical
      mastectomy, clinically and radiologically presenting as a primary sinonasal mass.
      Only the histopathologic examination together with a broad spectrum of
      immunohistochemical antibodies were useful in confirming the origin of the
      neoplasm.

PMID- 15468997
TI  - Cranio-cervical necrotizing fascitiis: case report and review of the literature.
AB  - Necrotising fascitiis is a rapidly progressive bacterial infection of the soft
      tissues and generally attacks the walls of the abdomen, the perineum, the limbs
      or, to a lesser degree, the cranio-cervical area. In the latter region, the
      infection involves the soft tissues of the neck, in a more or less extensive
      manner, and causes diffuse necrosis. Crepitation, areas with linear infiltration
      and others with fluctuation are detected on manual examination. Systemic symptoms
      such as fever, tachycardia, tachypnoea and signs of septic shock are always
      present, at least during the more advanced stages of the disease. Computed
      tomography may prove fundamental since it reveals an increase in the thickness
      and degree of impregnation of the cervical soft tissues, as well as the presence
      of liquid or gaseous infiltration in the thoracic areas, especially in cases of
      mediastinitis. Personal experience in a case is described which led to a review
      of the literature. The best approach in the management of this devastating
      condition is early diagnosis, adequate antibiotic treatment and radical surgical
      procedures, which may often need to be repeated several times.

PMID- 15468999
TI  - Pauci-symptomatic large epidermoid cyst of cerebellopontine angle: case report.
AB  - It is estimated that 10% of intra-cranial tumours are localized in the
      cerebellopontine angle and internal auditory canal and early symptoms of the
      different histological forms are almost identical. Acoustic neuroma account for
      90% and meningioma for 5-10% of these tumours, while a small percentage of rare
      tumours exist, the most frequent being epidermoid cyst, also known as congenital
      cholesteatoma or keratoma. The case is reported here of a large epidermoid cyst
      of the right cerebellopontine angle, and the clinical-radiological course is
      reviewed. The patient, a 35-year-old, male, initially presented an episode of
      objective rotatory vertigo, and a history of right ear fullness, of a few months'
      duration, with normal otoscopy. Audiometric test was normal in left ear, while
      slight pantonal sensori-neural hypoacusia was observed in the right ear. The
      impedenzometric findings were normal as was the vestibular test. Auditory
      brainstem evoked response showed an increased latency of fifth wave. Gadolinium
      enhanced magnetic resonance imaging of brain revealed the presence of a
      voluminous epidermoid cyst occupying the extra-axial side of the right
      cerebellopontine cistern with superior extension into the cistern. Due to the low
      grade of symptoms, we had chosen to wait and not perform surgery immediately,
      with otologic and vestibular test-controls every 6 months, with cerebral magnetic
      resonance imaging to control extension of the mass, without radiation exposure
      for the patient. One year after diagnosis, at the last control, otofunctional
      findings were not modified and repeat magnetic resonance imaging did not
      demonstrate important variations compared to the first. Thus, the choice not to
      proceed with surgery was justified since surgery is burdened by the risk of
      important complications. At magnetic resonance imaging, the epidermoid cyst,
      unlike the majority of intra-cranial tumours, such as acoustic neuroma and
      meningioma, does not show gadolinium-enhancement; this again supporting the
      important role of magnetic resonance imaging in the differential diagnosis of
      intra-cranial neoformations. It is, therefore, worthwhile stressing the validity
      of the approach, step by step, in the diagnosis of patients with otologic
      symptoms, together with the importance of magnetic resonance imaging that, in
      comparison with computed tomography, allowed us to exactly assess the growth rate
      of the mass and to "wait and see" without risks and without radiations for the
      patient.

PMID- 15469000
TI  - [Use of hydrocolloid plates for skin protective fixation of the nasal tube in
      oral CPAP].

PMID- 15469001
TI  - [The concept of tender care of premature infants--a review].

PMID- 15469002
TI  - [Peritoneal dialysis after cardiac surgical procedures].

PMID- 15469003
TI  - [Effects of noise and light on early child development and possibilities of noise
      and light reduction in premature infant intensive care units].

PMID- 15469004
TI  - [Febrile seizures--an update].
AB  - Febrile seizures are most common seizures in childhood (2-4%). Children with
      simple febrile seizures only have a slightly increased risk of epilepsy.
      Recurrences are common. Diagnostic ascertainment is easy, most evaluations
      simple, diagnostic routine schedules almost not necessary. Prophylactic
      antipyretic or anticonvulsant therapies are not recommended. Administration of
      rectal diazepam at home in case of recurrence is useful. Adequate therapeutical
      approach also includes physicians guidance and information for the dramatically
      frightened parents who think their child was about to die. Only complex febrile
      seizures with high risk of subsequent epilepsy may indicate intermittent diazepam
      prophylaxis or even continuous anticonvulsant treatment in case of a beginning
      epileptic syndrome.

PMID- 15469005
TI  - [The Germans die out. How the pension problem solves itself].

PMID- 15469006
TI  - [Isolation and characterization of fragments of ATP-dependent protease Lon from
      Escherichia coli obtained by limited proteolysis].
AB  - Conditions of limited proteolysis of the protease Lon from Escherichia coli that
      provided the formation of fragments approximately corresponding to the enzyme
      domains were found for studying the domain functioning. A method of isolation of
      the domains was developed, and their functional characteristics were compared.
      The isolated proteolytic domain (LonP fragment) of the enzyme was shown to
      exhibit both peptidase and proteolytic activities; however, it cleaved large
      protein substrates at a significantly lower rate than the full-size protease Lon.
      On the other hand, the LonAP fragment, containing both the ATPase and the
      proteolytic domains, retained almost all of the enzymatic properties of the full
      size protein. Both LonP and LonAP predominantly form dimers unlike the native
      protease Lon functioning as a tetramer. These results suggest that the N-terminal
      domain of protease Lon plays a considerable role in the process of the enzyme
      oligomerization.

PMID- 15469007
TI  - [An ACTH-like peptide immunocortin: effect on the activity of cells from the rat
      adrenal cortex].
AB  - The effect of immunocortin, an ACTH-like decapeptide VKKPGSSVKV corresponding to
      the 11-20 sequence of the variable part of the human IgG1 heavy chain on the
      content of 11-hydroxycorticosteroids (CS) in rat adrenal glands and blood serum
      in vivo was studied. An intramuscular injection of immunocortin at a dose of 10
      microg/kg was found in an hour to induce a twofold decrease in CS content in the
      adrenal glands and a 1.8-fold increase in the blood serum CS content. At the same
      time, an immunocortin dose of 100 microg/kg exerted practically no effect on the
      CS content and its dose of 1000 microg/kg increased the CS content both in
      adrenal glands and in blood serum by 1.6 and 2.2 times, respectively. Four hours
      after the injection of any of the three doses of immunocortin, the CS content in
      adrenal glands did not differ from the control value, and after 24 h the content
      decreased threefold. Immunocortin was shown to be bound by the ACTH receptors in
      the membranes of the rat adrenal cortex with a high affinity and specificity
      (inhibiting the specific binding of 125I-labeled ACTH-(11-24) peptide with Ki of
      1.2 nM).

PMID- 15469009
TI  - [Conjugates of the Ca2+ -regulated photoprotein obelin with immunoglobulins:
      synthesis and use as labels in bioluminescent immunoassay].
AB  - An efficient procedure for obelin conjugation with immunoglobulins was developed.
      The possibility was shown of using the resulting conjugates instead of a
      radioisotope label for the immunoassay of thyroid stimulating hormone in sera;
      the conjugates provide a sensitivity of 0.01 microIU/ml. The results of
      bioluminescent immunoassay (sera of 34 patients) satisfactorily correlate with
      the results of radioisotope assay (R 0.99).

PMID- 15469008
TI  - [Induction of immune response by synthetic fragments of the bovine prion protein
      and their analogues in mice of various lines].
AB  - The antibodies to the bovine prion protein were produced by immunizing mice of
      three lines with five synthetic fragments of the protein and their six analogues.
      The analogues contained the amino acid substitutions that, according to
      theoretical calculation, should lead to an increase in the immunogenic activity
      of peptides. All the peptides, except for one, induced the formation of
      antibodies. All the sera containing the antipeptide antibodies were tested by an
      immunohistochemical method. The sera that were effectively bound to the brain
      preparations from the bovine with spongiform encephalopathy were identified; it
      was shown that they do not interact with the preparations of normal brain.
      Therefore, it was shown that the immunization of mice with the synthetic
      fragments of a prion protein helps obtain specific antibodies suitable for the
      study and diagnostics of prion diseases.

PMID- 15469010
TI  - [Photoreactive dTTP analogues as substrates for thermostable DNA polymerase from
      Thermus thermophilus B35].
AB  - Substrate properties of several dTTP analogues bearing a photoreactive 2-nitro-5
      azidobenzoyl (NAB) group attached at position 5 of uracil through linkers of
      various lengths, dTTP-NAB-x-dUTP (where x = 2, 4, 7-13 is the number of atoms in
      the linker), were studied. All the analogues are substrates for thermostable
      Thermus thermophilus B35 DNA polymerase in the elongation reaction of the 5'-32P
      labeled primer-template complex. The kinetic parameters of some of the analogues
      were determined and compared with those of natural dTTP. It was shown that an
      increase in the linker length results in a higher efficiency of the analogue. The
      incorporation of NAB-x-dUMP residues into the 3'-primer end did not impede a
      further elongation of the chain in the presence of natural dNTP.

PMID- 15469011
TI  - [Polyfunctional molecules and their components in the processes of aromatic
      nucleophilic substitution. II. Nucleophilic modification of 3',5'-bis-O
      (alpha,beta,alpha',beta'-tetrafluoropyridyl-gamma)thymidine].
AB  - The interaction of 3',5'-bis-O-(alpha,beta,alpha',beta'-tetrafluoropyrid-gamma
      yl)thymidine with various nucleophilic reagents was studied to evaluate the
      possibility of molecular design of new types of nucleic acid analogues using SNAr
      reactions. The reactions with morpholine and sodium azide led to the introduction
      of one and two nucleophilic residues into each of the polyfluorinated pyridine
      rings. The nucleophilic polycondensation with bifunctional reagents
      ethylenediamine and hexamethylenediamine depended on the nature of nucleophile
      and reaction conditions and resulted in the formation of supramolecules
      containing about five or more than 20 pyrimidine bases.

PMID- 15469012
TI  - [A comparative analysis of regulatory regions of the transthyretin gene in the
      mouse, human, and chimpanzee genomes].
AB  - A full genome analysis of differences between the gene expression in the human
      and chimpanzee brains revealed that the gene for transthyretin, the carrier of
      thyroid hormones, is differently transcribed in the cerebella of these species. A
      7-kbp DNA fragment of chimpanzee was sequenced to identify possible regulatory
      sequences responsible for the differences in expression. One hundred and thirteen
      substitutions were found in the chimpanzee sequence in comparison with the human
      sequence. About 40% of the substitutions were revealed within the repeating
      elements of the genome; their location and sizes did not differ from those in the
      corresponding fragments of the human genome, and the nucleotide sequences had a
      high degree of identity. A comparison of nucleotide sequences of the
      transthyretin region of human, chimpanzee, and mouse genes revealed substantial
      differences in the distribution of G + C content along the examined fragment in
      the human (chimpanzee) and mouse genes and allowed us to localize three sequence
      tracts with a higher degree of identity in the three species. One of these tracts
      is located in the promoter region of the gene, and the other two probably
      determine the specificity of transthyretin gene expression in the liver and
      brain. One of the conserved tracts of the chimpanzee genome was found to have a
      single and a triple nucleotide substitution. The triple substitution
      distinguishes chimpanzees from humans and mice, which have identical sequences of
      this site. It is likely that these substitutions are responsible for the
      differences in the expression levels of the transthyretin gene in the human and
      chimpanzee brains.

PMID- 15469013
TI  - [Localization of matrix-associated elements in the 5'-region of the rat estrogen
      sulfotransferase gene].
AB  - Potential matrix-associated elements in the 5'-region of the rat estrogen
      sulfotransferase gene (Ste1) were searched for and characterized. The DNA
      fragments corresponding to the regions -800/+1048 and +1049/+2038 relative to the
      main point of transcription initiation were found to be bound to the nuclear
      matrix in vitro. A permanent association of the 5'-region of the Ste1 gene with
      the nuclear matrix in rat hepatocytes was found, the most probable site of
      attachment being the region -352/-152. No differences were found in the
      attachment of the 5'-region of the Ste1 gene to the nuclear matrix in the liver
      of males where the gene is actively transcribed and in that of females where it
      is inactive.

PMID- 15469014
TI  - [Tryptophan 7-halogenase from Pseudomonas aureofaciens ACN strain: gene cloning
      and sequencing and the enzyme expression].
AB  - The gene of tryptophan 7-halogenase was isolated from the Pseudomonas
      aureofaciens ACN strain producing pyrrolnitrin, a chlorocontaining antibiotic,
      and sequenced. A high homology degree (over 95%) was established for the genes
      and the corresponding halogenases from P. aureofaciens ACN and P. fluorescens
      BL915. The tryptophan 7-halogenase gene was amplified by PCR, and the
      corresponding enzyme was expressed in Escherichia coli cells using the pBSII SK+
      vector.

PMID- 15469015
TI  - [Sialylation of N-carbohydrate chains of glycoproteins with immobilized trans
      sialidase from Trypanosoma cruzi].
AB  - Alpha2,3-sialylation of the lactosamine type N-glycans with trans-sialidase from
      Trypanosoma cruzi is reported. Trans-sialidase (160 kDa, pI 5.35-5.65) and its
      catalytic fragment (70 kDa, pI 6.0-6.3) were isolated from T. cruzi cells and
      immobilized on ConA-Sepharose. The resulting preparation retained activity for
      several months and was repeatedly used for obtaining mono-, di-, tri-, and
      tetrasialylated 7-amino-4-metylcoumarine-labeled oligosaccharides with various
      numbers of antennas and for alpha2,3-sialylation of glycans within glycoproteins
      and neoglycoconjugates.

PMID- 15469016
TI  - [Elucidation of structure of lipid A from the marine Gram-negative bacterium
      Pseudoalteromonas haloplanktis ATCC 14393T].
AB  - The chemical structure of lipid A from the marine gamma-proteobacterium
      Pseudoalteromonas haloplanktis ATCC 14393T, a main product of lipopolysaccharide
      hydrolysis (1% AcOH), was determined using chemical methods and NMR spectroscopy.
      The lipid A was shown to be beta-1,6-glucosaminobiose 1,4'-diphosphate acylated
      with two (R)-3-hydroxyalkanoic acid residues at C3 and C3' and amidated with one
      (R)-3-hydroxydodecanoyl and one (R)-3-dodecanoyloxydodecanoyl residue at N2 and
      N2', respectively.

PMID- 15469017
TI  - [Photobiological properties of 13,15-N-(carboxymethyl)- and 13,15-N-(2
      carboxyethyl)cycloimide derivatives of chlorin p6].
AB  - Lipophilic derivatives of chlorin p6, 13,15-N-(carboxymethyl)cycloimide methyl
      ester (CIC1) and 13,15-N-(2-carboxyethyl)cycloimide methyl ester (CIC2), were
      shown to absorb light in 710 nm region and to be efficient IR photosensitizers.
      They exhibit similar phototoxicities on the cells of A549 human lung
      adenocarcinoma, which are 40- and 100-fold higher than those of chlorin p6 and
      the clinically used Photogem, respectively, and are not toxic in the absence of
      light irradiation. The confocal spectral imaging technique allowed us to
      demonstrate that the high phototoxicity of CIC1 and CIC2 is due to their ability
      to readily penetrate to cells and to be bound to the cell membranes and lipid
      containing structures in the monomeric photoactive form. Under the irradiation,
      the membrane-bound CIC1 and CIC2 are characterized by high quantum yields of
      singlet oxygen generation (0.6 and 0.65, respectively) and the inability to
      produce hydroxyl radicals. A 1.5-microM content of CIC1 and CIC2 in the
      incubation medium provides for their average cytoplasmic concentrations of 21 and
      16.5 microM, respectively. The incubation times to achieve 50% level of maximum
      accumulation for CIC1 and CIC2 in A549 cells are 30 +/- 6 and 24 +/- 12 min, and
      the times for 50% release of the dyes from the cells are 17 +/- 4 and 50 +/- 10
      min, respectively. A diffuse distribution with the predominant accumulation in
      the membranes of the Golgi apparatus and mitochondria is characteristic of both
      CIC2 and CIC1, whereas, in addition, CIC1 is considerably accumulated in lipid
      droplets (cellular organelles responsible for the storage and metabolism of
      neutral lipids and steryl esters). Our results demonstrate that changes in the
      structure of the imide substituent could affect the intracellular localization
      and the rate of release of chlorin p6 cycloimide derivatives from cells while
      preserving their high photodynamic activity.

PMID- 15469018
TI  - [Effect of genistein and daidzein obtained by acid hydrolysis of their glycosides
      on phospholipid peroxidation].
AB  - A mixture of isoflavones was obtained by acid hydrolysis of isoflavone glycosides
      isolated from the products of soybean processing by a successive extraction with
      aqueous acetone and methanol. Homogeneous isoflavones genistein and daidzein were
      isolated from the aglycone mixture by adsorption chromatography and identified by
      spectral and chromatographic methods. The effect of both isoflavones on lipid
      peroxidation of soy phospholipids in multilamellar vesicles was studied at
      various concentrations. These aglycones were found to inhibit the formation of
      lipid hydroperoxides and malonic dialdehyde at the concentrations as low as 1 mM.

PMID- 15469019
TI  - [Hydrophobic nitroxyl radicals inhibit linoleyl alcohol oxidation by 5
      lipoxygenase].
AB  - The linoleyl alcohol oxidation catalyzed by potato tuber 5-lipoxygenase was found
      to be efficiently inhibited by stable nitroxyl radicals: 1-oxyl-2,2,6,6
      tetramethylpiperidin-4-yl 1-bicyclo[2,2,2]octane-1-carboxylate, 1
      adamantylacetate, dodecanoate, and octadecanoate. The dependence of apparent IC50
      values on the rotational correlation times of times of 4-hydroxy-1-oxyl-2,2,6,6
      tetramethylpiperidine and its derivatives in model micellar systems was analyzed.
      The inhibition mechanism was proposed; it involves the interaction of hydrophobic
      nitroxyl radical with the intermediate radical enzyme-substrate complex.

PMID- 15469020
TI  - [A new synthesis of alpha-methylspermidine].
AB  - A five-step synthesis of alpha-methylspermidine (1,8-diamino-5-azanonane), the
      first polyamine analogue preventing pathological consequences of spermidine
      depletion in transgenic rats overproducing spermine/spermidine N'
      acetyltransferase, from ethyl 3-aminobutyrate was achieved in a high overall
      yield.

PMID- 15469021
TI  - [DNA-specific dimeric bisbenzimidazole].
AB  - A dimeric analogue of the fluorescent dye Hoechst 33258 was synthesized. It was
      shown to differentially stain human chromosome preparations and bind to double
      stranded DNAs.

PMID- 15469022
TI  - Epidemiology: quo vadis?
AB  - In our etiologic research, we epidemiologists need to leave behind the concepts
      of 'cohort' study and 'case-control' study and adopt that of the etiologic study
      as the singular substitute for these. We then need to realize that the etiologic
      study is well suited to be viewed as paradigmal for intervention studies. We
      finally need to become serious about object design before methods design in both
      etiologic and intervention research. Once these developments have occurred, we'll
      be ready for truly meaningful research to advance the knowledge base of both
      types of causality-oriented 'gnosis' in the practice of clinical medicine,
      etiognosis and intervention-prognosis; and descriptive-prognostic study we'll see
      as inherent in any intervention-prognostic study. As for diagnostic research,
      then, we need to come to see it as nothing but a special case of our familiar
      descriptive prevalence research. Because of this readily attainable theoretical
      readiness peculiar to us research epidemiologists, and for other reasons besides,
      only we can assume the central role in the production of the knowledge base for
      scientific medicine. We consequently have the obligation to assume this larger
      and higher, meta-epidemiologic mission--and some even higher ones besides.

PMID- 15469023
TI  - Epidemiology: more than etiology.

PMID- 15469024
TI  - Epidemiology: quo statis?

PMID- 15469025
TI  - Caminante no hay camino, se hace camino al andar.

PMID- 15469026
TI  - Epidemiology: populations, methods and theories.

PMID- 15469027
TI  - Epidemiologic methods: beyond clinical medicine, beyond epidemiology.

PMID- 15469028
TI  - Miettinen's epidemiology: quo vadis?

PMID- 15469029
TI  - Epidemiology in the right direction: the importance of descriptive research.

PMID- 15469030
TI  - Comment on Miettinen: Rose revisited.

PMID- 15469031
TI  - Epidemiology: indeed "quo vadis"?

PMID- 15469032
TI  - Loss to follow-up in cohort studies: how much is too much?
AB  - Loss to follow-up is problematic in most cohort studies and often leads to bias.
      Although guidelines suggest acceptable follow-up rates, the authors are unaware
      of studies that test the validity of these recommendations. The objective of this
      study was to determine whether the recommended follow-up thresholds of 60-80% are
      associated with biased effects in cohort studies. A simulation study was
      conducted using 1000 computer replications of a cohort of 500 observations. The
      logistic regression model included a binary exposure and three confounders.
      Varied correlation structures of the data represented various levels of
      confounding. Differing levels of loss to follow-up were generated through three
      mechanisms: missing completely at random (MCAR), missing at random (MAR) and
      missing not at random (MNAR). The authors found no important bias with levels of
      loss that varied from 5 to 60% when loss to follow-up was related to MCAR or MAR
      mechanisms. However, when observations were lost to follow-up based on a MNAR
      mechanism, the authors found seriously biased estimates of the odds ratios with
      low levels of loss to follow-up. Loss to follow-up in cohort studies rarely
      occurs randomly. Therefore, when planning a cohort study, one should assume that
      loss to follow-up is MNAR and attempt to achieve the maximum follow-up rate
      possible.

PMID- 15469033
TI  - Bootstrap investigation of the stability of disease mapping of Bayesian cancer
      relative risk estimations.
AB  - BACKGROUND: Bayesian approaches to disease mapping of relative risks are useful
      for rare disease when geographical units have very different population sizes. As
      Bayesian approaches may induce very different estimations, it is useful to
      consider the stability of the estimations as a criterion for evaluating the
      quality of the results. MATERIAL: Cancer incidence data, from the Isere cancer
      registry (France) over the 1985-1994 period, have been used to check the proposed
      method: the study is based on 22 cancer sites among males and 24 among females.
      METHOD: A bootstrap approach has been retained to evaluate the stability of the
      estimations. The coefficient of variation was chosen as an indicator of
      stability. Three Bayesian models corresponding to global, local and combined
      smoothing techniques, have been considered. The stability analysis has taken
      account of the results of spatial autocorrelation and heterogeneity tests.
      RESULTS: Bayesian approaches do not necessarily lead to stable estimations. The
      local smoothing approach induces estimations that are often unstable. The global
      smoothing approach is the most stable, but is conservative. Combined smoothing
      appears to be a good compromise if significant spatial variations and
      heterogeneity of relative risks exist. CONCLUSION: Bayesian estimations of
      relative risks may be very unstable. However, when results of spatial
      autocorrelation and heterogeneity tests are taken into account to choose between
      the different Bayesian approaches, instability becomes negligible.

PMID- 15469034
TI  - Longitudinal data analysis. A comparison between generalized estimating equations
      and random coefficient analysis.
AB  - The analysis of data from longitudinal studies requires special techniques, which
      take into account the fact that the repeated measurements within one individual
      are correlated. In this paper, the two most commonly used techniques to analyze
      longitudinal data are compared: generalized estimating equations (GEE) and random
      coefficient analysis. Both techniques were used to analyze a longitudinal dataset
      with six measurements on 147 subjects. The purpose of the example was to analyze
      the relationship between serum cholesterol and four predictor variables, i.e.,
      physical fitness at baseline, body fatness (measured by sum of the thickness of
      four skinfolds), smoking and gender. The results showed that for a continuous
      outcome variable, GEE and random coefficient analysis gave comparable results,
      i.e., GEE-analysis with an exchangeable correlation structure and random
      coefficient analysis with only a random intercept were the same. There was also
      no difference between both techniques in the analysis of a dataset with missing
      data, even when the missing data was highly selective on earlier observed data.
      For a dichotomous outcome variable, the magnitude of the regression coefficients
      and standard errors was higher when calculated with random coefficient analysis
      then when calculated with GEE-analysis. Analysis of a dataset with missing data
      with a dichotomous outcome variable showed unpredictable results for both GEE and
      random coefficient analysis. It can be concluded that for a continuous outcome
      variable, GEE and random coefficient analysis are comparable. Longitudinal data
      analysis with dichotomous outcome variables should, however, be interpreted with
      caution, especially when there are missing data.

PMID- 15469035
TI  - Social class, race/ethnicity and all-cause mortality in the US: longitudinal
      results from the 1986-1994 National Health Interview Survey.
AB  - BACKGROUND: Occupational social class has become a leading indicator of social
      inequalities in health. In the US, economic sectors are distinct with respect to
      wages, benefits, job security, promotion ladders and working conditions. The
      growing economic sector of self-employed workers is characterized by lower wages
      and benefits, and greater job insecurity. Little attention has been given to the
      association between economic sector measures of social class and all-cause
      mortality, and there have been no studies of mortality among the self-employed.
      METHODS: To determine risk of death associated with economic sector social class,
      this study entails a longitudinal analysis of the National Health Interview
      Survey (NHIS), an annual household survey representative of the US population for
      the period 1986-1994 (n = 377,129). The sample includes 201,566 men and 175,563
      women, aged 24-65 years of age, in the civilian labor force. RESULTS: Non-
      professionals are at higher risk of death than professionals across all sectors
      and self-employed professionals are at higher risk of death than professionals
      employed in government and production. Additional social class differences are
      accounted for by age, race, gender and marital status. Results are also partially
      explained by income. After controlling for income, Black professionals did not
      show a lower risk of death than Black non-professionals and self-employed
      Hispanic professionals had a higher risk of death than Hispanic professionals
      employed in the private sector. CONCLUSIONS: Given the growth of self-employment
      in the US, the noted increased risk of death among self-employed professionals
      merits further investigation and monitoring.

PMID- 15469036
TI  - Bone mass density and risk of breast cancer and survival in older women.
AB  - STUDY OBJECTIVE: Older women with high bone mineral density (BMD) have an
      increased risk of breast cancer but it is not well known whether this association
      is associated with the stage of the tumor. The objective of the study is to
      determine if older women with high BMD are likely to develop a more aggressive
      form of breast cancer, as defined by mortality. PATIENTS: We prospectively
      studied 1504 women who were 75 years of age or older at the entry in the study
      (range, 75-90 years), between 1992 and 1994. BMD was measured by dual-photon X
      ray absorptiometry at three skeletal sites (trochanter, Ward's triangle, femoral
      neck). The women were followed for a mean of 7 years for the occurrence of breast
      cancer. Cox proportional-hazards models were used to obtain estimates of the
      relative risk of breast cancer and relative risk of death according to the BMD.
      MAIN RESULTS: Forty-five incident breast cancer cases were identified. In
      multivariate analyses of the risk of breast cancer for women in the highest
      tertile of BMD was greater than for women in the lowest tertile. Indeed, the
      women with a trochanter BMD in the highest tertile were at 2.3-fold increased
      risk compared with women in the lowest tertile. The women with highest tertile
      BMD measured at the Ward's triangle and at the femoral neck were respectively at
      2.2-and 3.3-fold increased risk compared with women at the lowest risk. The 7
      year survival rates were markedly less favorable for women in the second and
      third tertile of the three skeletal sites compared with the lowest tertile. The
      risk of death was greater for women in the highest tertile of BMD than for women
      in the lowest tertile at every skeletal site. CONCLUSION: Elderly women with high
      BMD have an increased risk of breast cancer, especially advanced cancer, compared
      with women with low BMD.

PMID- 15469037
TI  - Polychlorinated biphenyls and breast cancer risk by combined estrogen and
      progesterone receptor status.
AB  - Studies have suggested that breast cancer risk factor profiles may vary according
      to joint estrogen receptor (ER) and progesterone receptor (PR) tumor status. Most
      of the published literature to date which has investigated the association
      between exposure to organochlorine compounds and breast cancer has reported null
      or weak associations. If, indeed, the classification by hormonal receptor status
      identifies different forms of breast cancer, then assessing the risk of exposure
      to polychlorinated biphenyls (PCBs) on breast cancer as one disease or
      stratifying based on ER or PR status alone may obscure the association between
      PCBs and breast cancer. A hospital-based case-control study of 266 cases and 347
      benign breast disease controls was conducted to examine the association of blood
      serum and adipose tissue concentrations of PCBs with breast cancer by joint ER/PR
      status. Total PCBs were measured in blood serum, and the following PCB congeners
      were measured in breast adipose tissue: 74, 118, 138, 153, 156, 170, 180, 183,
      187. We did not detect any clear relationship or change in breast cancer risk
      based on joint ER/PR tumor status for body burden of PCBs, whether measured in
      blood serum or breast adipose tissue, by total PCBs or for specific congeners.
      These results confirm previous findings in the literature of no positive
      association between environmental exposure to PCBs and risk of breast cancer.

PMID- 15469038
TI  - The association of body mass index and waist circumference with blood pressure
      depends on age and gender: a study of 10,928 non-smoking adults in the Greek EPIC
      cohort.
AB  - Body mass index (BMI) and waist circumference are independently associated with
      blood pressure, but the dependence of these associations on gender and age has
      not been clarified. We investigated the associations of BMI and waist
      circumference with systolic (SBP) and diastolic (DBP) blood pressure and assessed
      possible interactions with gender and age. Data concerning blood pressure and
      anthropometric variables were collected at enrollment in a cohort study from
      10,928 non-smoking adults, all over Greece, who have never received
      antihypertensive treatment. Multiple regression-derived standardized coefficients
      were estimated to compare effects among variables. Among men, waist circumference
      appears more important than BMI in the prediction of SBP (standardized
      coefficients 2.26 vs. 1.52 mmHg/SD), and to a lesser extent DBP. In contrast,
      among women, BMI is more important than waist circumference, in the prediction of
      SBP (standardized coefficients 3.97 vs. 1.56 mmHg/ SD) and to a lesser extent
      DBP. The different effects of BMI and waist circumference on blood pressure by
      gender are evident among older individuals (> 55 years); among younger
      individuals BMI and waist circumference have comparable effects in both genders.
      Among younger individuals, BMI and waist circumference are independent and
      equally important predictors of SBP and DBP in both genders, whereas among older
      individuals waist circumference is the dominant predictor of blood pressure among
      men and BMI is the dominant predictor of blood pressure among women. Associations
      are more evident with respect to SBP than DBP.

PMID- 15469039
TI  - Why do some countries publish more than others? An international comparison of
      research funding, English proficiency and publication output in highly ranked
      general medical journals.
AB  - National factor(s) influencing publication output in the highest ranked medical
      journals are largely unknown. We sought to examine the relationship between
      national research funding and English proficiency on publication output. We
      identified all original research articles appearing in the five highest ranked
      general medical journals between 1997 and 2001. Using the country of the
      corresponding author as the source nation for each article, we determined a
      standardized publication rate across developed nations. We used multiple
      regression techniques to determine the influence of national expenditures on
      research and scores from the Test of English as a Foreign Language (TOEFL), a
      surrogate for English proficiency, on publication output. There was a significant
      relationship of national spending on research and TOEFL scores to publication
      output of developed countries (p = 0.04; p < 0.01, respectively). These two
      variables explained approximately 71.5% of the variation in publication rate
      across developed nations around the world (R = 0.85; p < 0.01). Normalized for
      population size, English-speaking nations and certain northern European countries
      such as Denmark, The Netherlands, Switzerland, and Sweden had the highest rate of
      publication in the five highest ranked general medical journals, while Asian
      countries had generally low rates of publication. Research spending and English
      proficiency were strongly associated with publication output in the highest
      ranked general medical journals. While these data cannot be considered definitive
      due to their observational nature, they do suggest that for English-language
      medical journals, research funding and English proficiency may be important
      determinants of publication.

PMID- 15469040
TI  - Snus is not harmless!

PMID- 15469041
TI  - Regulation mechanisms of vanilloid receptors.
AB  - The capsaicin receptor TRPV1 (also known as the vanilloid receptor VR1) is a non
      selective cation channel and is activated not only by capsaicin but also by
      noxious heat or protons. Tissue damage associated with infection, inflammation or
      ischaemia, produces an array of chemical mediators that activate or sensitize
      nociceptor terminals. An important component of this pro-algeic response is ATP.
      In cells expressing TRPV1, ATP increased the currents evoked by capsaicin or
      protons through activation of P2Y metabotropic receptors in a PKC-dependent
      manner. In the presence of ATP, the temperature threshold for TRPV1 activation
      was reduced from 42 degrees C to 35 degrees C, such that normal body temperature
      could activate TRPV1. Functional interaction between P2Y receptors and TRPV1 was
      confirmed in a behavioural analysis using TRPV1-deficient mice. Direct
      phosphorylation of TRPV1 by PKC was confirmed biochemically and the two serine
      residues involved were identified. Extracellular Ca2+ -dependent desensitization
      of TRPV1 is thought to be one mechanism underlying the paradoxical effectiveness
      of capsaicin as an analgesic therapy. The Ca2+ -binding protein calmodulin binds
      to the C-terminus of TRPV1. We found that disruption of the calmodulin binding
      segment prevented TRPV1 desensitization even in the presence of extracellular
      Ca2+.

PMID- 15469042
TI  - Sodium channels and neuropathic pain.
AB  - Although it has long been known that sodium channels play an important role in
      the generation of abnormal neuronal activity and neuropathic pain, it is only
      recently that we have begun to understand the subtypes of sodium channels which
      are particularly important in neuropathic pain. Many of the identified subtypes
      of sodium channels are localized in dorsal root ganglion (DRG) neurons. Based on
      their sensitivity to tetrodotoxin (TTX), these sodium channels are classified as
      TTX-sensitive (TTXs) or TTX-resistant (TTXr) subtypes. In in vitro
      electrophysiological experiments, ectopic discharges arising from DRG neurons
      with injured axons are blocked by TTX at doses that are too low to block TTXr
      subtypes. Furthermore, the same low doses of TTX applied to the DRG of the
      injured segment in neuropathic rats significantly reduce pain behaviours. These
      data suggest that TTXs subtypes of sodium channels are playing an important role
      in the generation of both ectopic discharges and neuropathic pain. Analysis of
      mRNA of the TTXs subtypes of sodium channels in the DRG after spinal nerve
      ligation showed that Nav1.3 (Type III) and Nax (NaG) are the only two subtypes
      that are up-regulated, suggesting their potentially important role in ectopic
      discharge and neuropathic pain generation.

PMID- 15469043
TI  - Ion channel activities implicated in pathological pain.
AB  - Altered expression of voltage-gated sodium, calcium and potassium channels has
      been associated with neuropathic pain conditions. In addition, roles for the
      ligand-gated P2X3 and NMDA receptors, as well as pacemaker HCN channels have also
      been invoked in the pathogenesis of neuropathic pain. In this chapter, evidence
      of an important role for post-translational regulation of Nav1.9 in setting pain
      thresholds is presented. Despite the importance of tactile allodynia and
      mechanical hyperalgesia in chronic pain, we remain ignorant of the molecular
      nature of mechanosensors present in sensory neurons. A number of candidate
      mechanosensor genes, identified because of their structural similarity with
      mechanosensors in Caenorbabditis elegans and Drosophila melanogaster have been
      identified. Acid-sensing ion channels (ASICs) are structurally related to
      putative mechanosensors in C. elegans, whilst transient receptor potential
      channels (TRPs) have been implicated in mechanosensation in the Drosophila
      acoustic system. Evidence against a role for ASICs as primary transducers of
      mechanosensation is provided here, and recent evidence implicating TRP channels
      is reviewed. Finally, the use of sensory neuron-specific gene deletion approaches
      to unravel the significance of individual ion channels in the regulation of
      sensory neuron excitability and the induction of pain will be described.

PMID- 15469044
TI  - Chronic pain and microglia: the role of ATP.
AB  - Pain following nerve damage is an expression of pathological operation of the
      nervous system, one hallmark of which is tactile allodynia. We have been studying
      the role of ATP receptors in pain, and have already reported that activation of
      the P2X2/3 heteromeric channel/receptor in primary sensory neurons causes acutely
      tactile allodynia. We report here that tactile allodynia under chronic pain
      states requires an activation of the P2X4 ionotropic ATP receptor and p38 mitogen
      activated protein kinase (MAPK) in spinal cord microglia. Two weeks after L5
      spinal nerve injury, rats displayed a marked mechanical allodynia. In the rats,
      activated microglia were detected in the injury side of the dorsal horn where the
      level of the dually phosphorylated active form of p38MAPK (phospho-p38MAPK) was
      increased. We performed the double-immunostaining analysis using cell-type
      specific markers and found that phospho-p38MAPK-positive cells were microglia.
      Moreover, intraspinal administration of p38MAPK inhibitor, SB203580, suppressed
      the allodynia. We also found that the expression level of P2X4 was increased
      strikingly in spinal cord microgila after nerve injury and that pharmacological
      blockade of P2X4 reversed the allodynia. Intraspinal administration of P2X4
      antisense oligodeoxynucleotide (ODN) reduced induction of P2X4 and suppressed
      tactile allodynia. Taken together our results demonstrate that activation of P2X4
      or p38 MAPK in spinal cord microglia is necessary for tactile allodynia following
      nerve injury.

PMID- 15469045
TI  - Neurotrophic influences on neuropathic pain.
AB  - Damage to peripheral nerves following trauma or disease has a number of
      consequences including the emergence of neuropathic pain. Commonly, neuropathic
      pain sufferers experience spontaneous burning pain in and radiating from the area
      innervated by the damaged nerves, and an exquisite sensitivity to light touch
      stimuli, which are now perceived as painful. These neuropathic pains are often
      refractory to conventional analgesic therapy, with most patients obtaining at
      best only partial relief. Unfortunately, neuropathic pains are frequently also
      very persistent and do not resolve with time. Thus, neuropathic pain is often an
      extremely debilitating condition with a bleak outlook. In this paper we review
      the pathophysiological mechanisms that underlie these neuropathic pain states
      with particular emphasis on the therapeutic role of neurotrophic factors.

PMID- 15469046
TI  - Changes in DRG neurons and spinal excitability in neuropathy.
AB  - An intracellular signalling pathway in the dorsal root ganglion (DRG) and spinal
      neurons is a popular target in pain research that is relevant to the neuroplastic
      changes that occur during chronic pain conditions. First, we examined the
      phosphorylation of ERK in DRG neurons after peripheral inflammation and sciatic
      nerve transection without any stimulation to the receptive field. We found an
      activation of ERK in different populations of DRG neurons after peripheral
      inflammation and axotomy, which developed from alterations in target-derived
      nerve growth factor (NGF). We observed that the ERK signalling regulates the
      brain-derived neurotrophic factor (BDNF) expression in DRG neurons in both
      conditions. We also demonstrated that very rapid phosphorylation of ERK occurred
      in DRG neurons that were involved in the transmission of various noxious signals
      under normal conditions. Further, we examined the pERK labelling after the
      mechanical stimuli into the inflamed tissue and found that the pERK labelling
      occurred through the P2X3 receptors in the terminals. This activity-dependent
      activation of the ERK signal pathway may be useful for identifying which DRG
      neurons are involved in transmission of noxious stimuli under normal and
      pathological conditions.

PMID- 15469047
TI  - Functional reorganization of the spinal pain pathways in developmental and
      pathological conditions.
AB  - Following inflammation, a subpopulation of Abeta afferents that terminates
      preferentially in deeper laminae have been shown to extend their axons to the
      superficial dorsal horn, particularly substantia gelatinosa (SG). Similarly, SG
      neurons in immature spinal cord receive mainly Abeta afferent inputs. To clarify
      whether the reorganized sensory pathway in the inflamed rats has a functional
      similarity with that in the developmental state, we compared synaptic inputs from
      primary afferents using in vitro and in vivo patch-damp recordings from SG
      neurons. SG neurons in the mature state had monosynaptic inputs from Adelta and C
      afferents, while only a few neurons received inputs from Abeta afferents.
      Following inflammation, the Abeta afferents extended their axons to SG and
      established functional monosynaptic transmission. Meanwhile, SG neurons in the
      immature state received preferentially Abeta as well as Adelta afferent inputs,
      and the majority of Abeta afferent inputs were monosynaptic. These observations
      support the idea that the sprouting of the large afferent fibres observed in
      inflamed rats is, at least in part, a regeneration process. However, the process,
      maybe distinct at some point from the process during development, therefore,
      produces pathological pain. Though the idea that the regeneration mimics the
      developmental process has been widely accepted, other possibilities cannot be
      excluded.

PMID- 15469048
TI  - Central plasticity in pathological pain.
AB  - Neurons and synapses in the central nervous systems are very dynamic and plastic,
      and can undergo changes throughout life. Studies of molecular and cellular
      mechanisms of such changes not only provide important insight into how we learn
      and store new knowledge in our brains, but also reveal the mechanisms of
      pathological changes occurring following an injury. Here, we propose that while
      neuronal mechanisms underlying physiological functions such as learning and
      memory may share some common signalling molecules with abnormal or injury-related
      changes in the brain, distinct synaptic mechanisms are involved in pathological
      pain as compared with that of cognitive learning and memory. Using genetically
      altered mice and classic physiological approaches, we showed that N-methyl-D
      aspartate (NMDA) receptor-dependent, calcium-calmodulin-activated adenylyl
      cyclases (AC1 and AC8) in the anterior cingulate cortex (ACC) play important
      roles in the induction and expression of persistent inflammatory and neuropathic
      pain. In contrast, acute pain was not significantly affected. Calcium-calmodulin
      dependent protein kinase IV, which is widely expressed in central areas related
      to pain and memory, primarily contributes to injury-related fearful memory and
      emotional responses. Our studies suggest distinct signalling pathways are
      responsible for physiological responses to the injury, including behavioural,
      emotional and memory.

PMID- 15469049
TI  - Anti-opioid systems in morphine tolerance and addiction--locus-specific
      involvement of nociceptin and the NMDA receptor.
AB  - Mechanisms for opioid tolerance and addiction are divided into two types of
      plasticity--cellular level and those occurring through multiple neuronal
      networks. Receptor desensitization through phosphorylation and endocytosis are
      currently well discussed using cell lines expressing opioid receptors in relation
      to acute tolerance mechanisms, while altered gene expression is mainly discussed
      in relation to the model mechanisms of chronic tolerance and dependence. However,
      little is known of mechanisms operating through plasticity of neuronal networks.
      In our approach, we began with the assumption that some non-opioid neurons with
      anti-opioid activity may cause neuronal plasticity, showing opioid adaptation and
      dependence. In mice lacking nociceptin/orphanin FQ receptor (NOP), or the NMDA
      receptor epsilon1 subunit, both of which mediate anti-opioid activities,
      analgesic tolerance and dependence following chronic morphine treatments were
      markedly attenuated. Chronic morphine-treatments increased NOP gene or epsilon1
      subunit protein expression in the spinal cord or specific brain loci,
      respectively. Furthermore the rescue of the epsilon1 subunit gene in the specific
      brain locus of knockout mice recovers the tolerance and dependence. All these
      results suggest that the enhanced anti-opioid system may contribute to the
      development of morphine tolerance and dependence, and their contribution could be
      brain locus specific.

PMID- 15469050
TI  - Chronic morphine-induced plasticity among signalling molecules.
AB  - Most formulations of the consequences of the persistent activation of opioid
      receptors have centred on the diminution or loss of opioid receptor-coupled
      signalling mechanisms. Activation of opposing compensatory circuits remains
      another of the adaptations proposed to underlie the extreme loss of the
      antinociceptive potency of narcotics following their chronic administration.
      Recent research has revealed that adaptations to chronic morphine involve not
      only the impairment of opioid receptor functionality but also the altered
      consequences of its G protein coupling. Pre-eminent among the biochemical
      perturbations that underlie the chronic morphine-induced emergence of new
      signalling strategies are enhanced phosphorylation and altered expression of key
      signalling molecules. These molecular changes include the up-regulation and
      augmented phosphorylation of adenylyl cyclase type II isoforms, which underlies
      the ability of morphine to shift opioid receptor G protein signalling from
      predominantly Gialpha inhibitory to Gbetagamma stimulatory. Persistent morphine
      exposure also enhances the concomitant phosphorylation of G protein receptor
      kinase, beta arrestin and the G protein Gbeta subunit, one consequence of which
      is to further enhance G protein receptor signalling via the Gbetagamma subunit.
      This review will focus on our increasing understanding of the importance of
      qualitative changes among components of opioid receptor-coupled signalling
      pathways, as opposed to the interruption of such signalling, as the predominant
      mode of adapting to the presence of opioids.

PMID- 15469051
TI  - Opioid tolerance and neuroplasticity.
AB  - Opioid analgesics are highly effective for treating many forms of acute and
      chronic pain. The development of opioid analgesic tolerance is a pharmacological
      phenomenon indicative of the cellular and system adaptation that could affect the
      clinical use of opioid analgesics. Activation of N-methyl-D-aspartate receptors
      and protein kinase C as well as regulation of glutamate transporters has been
      implicated in the mechanisms of opioid tolerance, suggesting a possible link
      between neural plasticity and the mechanisms of opioid tolerance. More recent
      studies have shown that neural plasticity associated with the development of
      opioid tolerance may activate a pronociceptive mechanism within the central
      nervous system that could counteract the analgesic effects of opioids. Thus,
      exposure to opioids could lead to two seemingly unrelated cellular processes,
      i.e. (1) the development of opioid tolerance--a negative sign of cellular
      adaptation, and (2) the development of opioid-induced pain sensitivity--a
      positive sign of cellular adaptation. The converging effects of these cellular
      mechanisms would significantly reduce the opioid analgesic efficacy. The current
      evidence also suggests new approaches for improving the clinical use of opioid
      analgesics.

PMID- 15469052
TI  - A mechanism-based understanding of bone cancer pain.
AB  - Although bone cancer pain can be severe and is relatively common, as it
      frequently arises from metastases from breast, prostate and lung tumours,
      relatively little is known about the basic mechanisms that generate and maintain
      this chronic pain. To begin to define the mechanisms that give rise to bone
      cancer pain, we developed a mouse model using the intramedullary injection and
      containment of osteolytic sarcoma cells into the mouse femur. These tumour cells
      induced bone destruction as well as ongoing and movement evoked pain behaviours
      similar to that found in patients with bone cancer pain. In addition, there was a
      significant neurochemical reorganization of sensory neurons that innervate the
      tumour bearing bone as well as in the spinal cord segments that received sensory
      input from the cancerous bone. This reorganization generated a neurochemical
      signature of bone cancer pain that was different from that observed in mouse
      models of chronic neuropathic or inflammatory pain. These data suggest that there
      is an inflammatory, neuropathic and tumorigenic component to bone cancer pain.
      Therefore defining when and how these different components drive bone cancer pain
      may allow the development of more selective analgesic agents to treat this
      chronic pain state.

PMID- 15469053
TI  - Mechanistic and clinical aspects of complex regional pain syndrome (CRPS).
AB  - Complex regional pain syndromes (CRPS, reflex sympathetic dystrophy, causalgia)
      are painful disorders that develop after trauma affecting a limb with (I) or
      without (II) nerve injury. Clinical features are pain, impairment of motor
      function, swelling and autonomic abnormalities (changes in sweating and blood
      flow). Autonomic abnormalities. The maximal skin temperature difference between
      the affected and unaffected extremity that occurs during a controlled
      thermoregulation can be used as a diagnostic tool. SMP. Sympathetic outflow to
      the painful extremity was experimentally activated. The intensity as well as area
      of spontaneous pain and mechanical hyperalgesia increased considerably in
      patients that had been classified as having SMP by positive sympathetic blocks. A
      pathological interaction between sympathetic vasoconstrictor and afferent neurons
      within the affected skin is the likely explanation for SMP in CRPS patients.
      Motor abnormalities. Kinematic analysis of target reaching as well as grip force
      analysis showed a pathological sensorimotor integration located in the parietal
      cortex. Furthermore, MEG studies demonstrated a continuous inhibition of the
      primary motor cortex. Neurogenic inflammation. Some features of acute CRPS
      (vasodilatation, swelling, pain) indicate a localized inflammatory process.
      Transcutaneous electrical stimulation of nociceptive C-fibre provoked protein
      extravasation into the interstitial fluid (microdialysis) only in CRPS patients
      and not in controls.

PMID- 15469054
TI  - Cortical pathophysiology of chronic pain.
AB  - Studies in my laboratory have been employing multiple non-invasive brain imaging
      techniques to study the characteristics of patients with chronic pain. Some of
      these results are briefly outlined in this communication. Our studies regarding
      brain activity in chronic pain are summarized, emphasizing the unique role of the
      prefrontal cortex in chronic, especially neuropathic pain states. I also review
      our work examining brain chemistry abnormalities in chronic pain. Given these
      results, we have examined chronic pain patients in a cognitive task, designed to
      probe brain regions that we think are specifically abnormal in chronic pain,
      these results are also summarized. An overview of the mechanisms that may be
      pertinent to the observed results is included.

PMID- 15469055
TI  - [Risk assessment of foodborne infections].
AB  - The microbiological risk assessment during production, processing and treatment
      of foods illustrates an important basis for the judgement of the safety of food
      products. Since the mid-nineties the concept of risk analysis according to Codex
      Alimentarius requirements ist pursued more intensely. Risk assessment is part of
      the risk analysis process besides risk management and risk communication. A
      strict separation between risk management and assessment should lead to a
      systematic, scientifically based and independent process without considering
      economic or political constraints whereas the decision on protective measures or
      the acceptance of risks lies in the responsibility of the managers. Risk
      assessment can only be successfully implemented in an interdisciplinary approach
      between physicians, veterinarians, microbiologists, molecularbiologists, food
      technologists, epidemiologists and mathematicians. Surveillance, monitoring
      programs and other data collections on a variety of parameters like statistics on
      foodborne human cases, the prevalence of zoonotic agents in animals, the
      distribution of micro-organisms in the environment and in foods, the behaviour of
      micro-organisms during food processing and the consumption habits of consumers
      deliver the necessary data for risk assessors. With the aim of mathematic
      modelling and simulation it is possible to calculate the probability of health
      problems in humans after the consumption of a foodstuff contaminated with a
      specific pathogenic micro-organism.

PMID- 15469056
TI  - [Are mycotoxins in food a health hazard?].
AB  - The effects of mycotoxins are well known since antiquity. Modern trace analysis
      show the wide prevalence of mycotoxins in the food chain. Aflatoxins (AFB1, AFB2,
      AFG1, AFG2), trichothecenes (deoxynivalenol, T-2 Toxin, HT-2 Toxin), zearalenone,
      fumonisins (FB1, FB2) and ochratoxin A are the most important mycotoxins world
      wide. Foods of plant origin are normally contaminated more frequently and in
      higher concentrations than food of animal origin. The mean concentrations of
      mycotoxins analysed in European foods can be assed as low. This may be one reason
      why acute poisonings are rare incidences and why the limits of the tolerable
      daily intake (TDI) levels are exceeded only very seldom; however the population
      group "infant" exceed the preliminary TDI-level for trichothecenes. The
      consequences of a chronic intake of low amounts of mykotoxins is hardly to
      assess. A participation of the aflatoxins in the pathogenesis of primary liver
      cancer is considered as certain. Other coherence between the dietary intake of
      mycotoxins and specific clinical symptoms of man are not convincingly shown till
      now.

PMID- 15469057
TI  - [Spread of viruses through the food chain].
AB  - Food associated viruses are responsible for a high number of infectious diseases
      in man, mainly gastroenteritis and hepatitis. The three most important viral
      agents are noroviruses (NV) (formerly known as Norwalk-like viruses), Rotavirus
      (RV) and Hepatitis A-Virus (HAV). The numbers of infections in man were in 2002
      according to the Robert Koch-Institut for NV and RV 50,000, respectively, and for
      HAV 1,500, slightly decreasing in 2003. The rate of foodborne infections caused
      by viruses can only be estimated (appr. 20% of total cases). On the other hand
      only a very small part of viral gastroenteritis can be diagnosed and notified.
      Besides the direct infection through contaminated food the human to human
      infection is the most important source, also responsible for outbreaks. There is
      at the moment no routine diagnostic tool available for the detection of viruses
      in food because of the lack of standardized methods. For NV, one of the most
      important foodborne (live bivalve molluscs) viral pathogens, indicator organisms
      are in use. There is a scientific evaluation in different member states
      concerning the value of bacterial indicators vs. bacteriophages. In addition to
      foodborne viruses (via faecal contamination present in the food chain) there are
      emerging zoonotic viral agents. Food may be a vector for this agents depending on
      the production structures (e.g. SARS or influenca).

PMID- 15469058
TI  - [Occurrence of enterohaemorrhagic E. coli (EHEC) in domestic animals].
AB  - Among the verocytotoxin producing E. coli strains (VTEC) the enterohemorrhagic
      group (EHEC) have emerged as important source of serious disease in human, e.g.
      the haemolytic uremic syndrome (HUS). VTEC strains possess different virulence
      profiles where by virulence traits can be provided by the chromosome, by plasmids
      and, in the case of verocytotoxins (except: VT2e) by bacteriophages. The original
      and main reservoir are ruminants. In Germany, VTEC strains were isolated in
      ruminant stocks regularly. In part, the prevalence was estimated up to 100%.
      However, strains of important EHEC serovar groups, e.g. O157, O26, O111, O103 and
      O145 as main source of human infections are isolated rarly. This is even the case
      for food originated from those animals. The hygienic management to avoid fecal
      contamination of carcasses during the slaughter process is of crucial importance.
      Future preventive strategies in the field of primary production may be the
      development of vaccination programs and/or the feeding management to reduce the
      shedding of acid resistant VTEC. Slowly recognized environmental sources of
      infection and contamination are biotic (e.g. flys, rodents) and abiotic factors
      (e.g. pasture, water, feed). In an own study that investigated the prevalence of
      VTEC positive animals in free range cows during sojourn on pasture a significant
      increase was estimated. Even asymptomatic human carriers can serve as source of
      infection or contamination.

PMID- 15469059
TI  - [The epidemiology of human enterohemorrhagic Escherichia coli infections in Lower
      Saxony].
AB  - BACKGROUND: In the German federal state Lower Saxony, data on infections with
      enterohemorrhagic Escherichia coli (EHEC) and hemolytic uremic syndrome (HUS) are
      collected systematically since 1997 based on reports by physicians and
      laboratories. Initially the data were collected by means of a specific
      established surveillance system, since 2001 they are collected as part of the new
      infectious disease law. RESULTS: From 1997 to 2003, in Lower Saxony 880 EHEC
      infections and 112 HUS-cases, 6 of whom died, were notified. This corresponds to
      an incidence of 1.6 EHEC-infections and 0.2 HUS-cases per 100000 person-years. No
      secular trend was observ-ed for the yearly number of HUS-cases, but raised
      numbers were observed for the years 1997 and 2002. There were strong regional
      differences of the EHEC/HUS-incidence from 0.7 in the district Braunschweig to
      3.5 in the district Weser-Ems. For 56% of reported EHEC-cases, serotype
      information was available. The most frequent serogroup was O157, accounting for
      30% of cases with serotype information. Of HUS-cases with known serotype, 86%
      were caused by O157, 20% by O157:H-. 52% of the EHEC-cases were less than 5 years
      old (HUS: 77%), and 68% less than 10 years (HUS: 92%). 23% of EHEC/HUS-cases
      could be identified as part of clusters with a mean number of 2.6 cases per
      cluster. These clusters almost exclusively affect-ed families. Though the data
      also contained information on possible sources or routes of infection, for none
      of the cases a microbiologically assured source was documented. CONCLUSIONS: The
      incidences of EHEC and HUS were higher in Lower-Saxony than in the whole of
      Germany. During the study period no significant trends concerning the number of
      HUS-cases or the distribution of serotypes were observed. More frequent
      serotyping and more complete information on sources or risks of infection should
      be achieved.

PMID- 15469060
TI  - [Coxiella burnetii as zoonotic pathogen with special regard to food hygiene].
AB  - In Hesse, Germany, bulk milk of farms producing raw milk cheese is examined by
      PCR for Coxiella burnetii yearly. In 2003 the pathogen has been detected
      unusually frequent. By means of two examples the hygienic measures are shown,
      which were initiated by the veterinary administration. To detect Coxiella
      burnetii means always the preoccupation with unsolved questions. It is
      particularly uncertain, whether there is a risk of oral infection for the human
      being. From the point of view of food hygiene, surveys are needed urgently to
      work out a risk assessment. Based on this a uniform risk management and a
      reasonable risk communication can be fixed.

PMID- 15469061
TI  - [Up-to-date information from the German QS salmonella monitoring and reduction
      programme].
AB  - In the beginning, the history, objectives and basic principles of the samonella
      monitoring and reduction programme that has been developed and implemented since
      2002 in the framework of the German cross-sectional quality management and
      assurance programme "QS" for the food chain are expained in detail. It is a semi
      quantitative assessment of the intra-herd prevalence of animals (60 samples per
      slaughter pig herd and year) with antibodies against salmonella species. By means
      of this asessment, herds are assigned to one of three risk categories (I = low
      risk, II = medium risk, and III = high risk) in terms of the probability to
      introduce Salmonella spp. into the food chain via slaughter pigs. The assignment
      to the categories is the basis of salmonella-reducing intervention measures. The
      implementation of the programme is considerably behind the schedule by mid-2004.
      The reasons for the delay are explained and conclusions for the further
      development of the programme are drawn.

PMID- 15469062
TI  - [Monitoring and risk assessment of campylobacter infections].
AB  - The aim of a national study of a "Quantitative Risk Assessment of Campylobacter
      infections and broiler chicken" at the Federal Institute for Risk Assessment is
      to estimate the chicken meat associated risk of Campylobacteriosis in Germany by
      using probabilistic models. Furthermore, process parameters (modelling
      parameters) with the most vital impact on the risk of Campylobacteriosis due to
      chicken meat have to be elaborated to give recommendations for risk management
      options in the whole food chain. The outcome of Joint FAO/WHO Expert
      Consultations on Risk Assessment of Microbiological Hazards in Foods (JEMRA) with
      respect to Campylobacter spp. in broiler chickens are the baseline for the
      national approach. In addition, national studies from Canada, Denmark and The
      Netherlands have to be considered. Typical regional data with respect to the
      disease, to risk factors in Germany and to the qualitative and quantitative
      occurrence of Campylobacter in broiler chickens along the "farm-to-fork"
      continuum have to be collected and validated for elaboration of the four elements
      of a risk assessment. Data on the prevalence of the agent at different stages of
      the food chain given in available surveillance systems in Germany are limited
      with respect to their suitability as incoming parameters for the models. A
      monitoring programme, as required in the Directive 2003/99/EC on the monitoring
      of zoonoses and zoonotic agents, as well as coordinated programmes for the
      official food control authorities, could improve the data baseline for risk
      assessment studies for instance. To collect all necessary information on the
      quantitative load of Camylobacter in broiler chickens will go beyond the scope of
      any existing or future monitoring systems. Results can only be achieved by
      detailed studies. Beside this, regional data on production and processing of
      broiler chicken, consumption data and information on the behaviour of consumers
      in households when preparing broiler chicken products are relevant for assessing
      the final risk to the consumers. For some questions, especially with respect to
      the dose-response-relation, internationally used models have to be applied. The
      national study is embedded in a national epidemiological network of "Foodborne
      Infections in Germany" which is coordinated by the Robert-Koch-Institute and
      supported by the Federal Ministry of Education and Research (BMBF).

PMID- 15469063
TI  - Risk assessment strategies for Europe: integrated safety strategy or final
      product control: Example of Listeria monocytogenes in processed products from
      pork meat industry.
AB  - The European regulation 2160/2003 of November 17th, 2003 clearly shows the
      European strategy of zoonosis monitoring and control as an integrated approach,
      including the entire food production chain with a first application to Salmonella
      control in different animal species. This regulation is the consequence of a risk
      assessment performed with a "farm to fork" philosophy. European strategy is
      scarcely different from the American strategy, despite the fact that both were
      achieved by a quantitative risk assessment, as for instance, in the USA the
      control of Salmonella in eggs is supposed to be completed by refrigeration.
      Nevertheless, the EU will still have a final product control approach towards
      future regulations on microbiological criteria for foodstuffs. The final
      production monitoring and control with HACCP (93/43/EC) and microbiological
      criteria is the only one available for L. monocytogenes in foodstuffs. The
      purpose of this paper is to discuss alternative control strategies for L.
      monocytogenes in pig production including integrated risk assessment. In France,
      most of the food-borne outbreaks associated with L. monocytogenes in delicatessen
      were due to one particular group of strains belonging to serovar 4b and
      presenting a particular RFLP/PFGE (Restriction Fragment Length
      Polymorphism/Pulsed Field Gel Electrophoresis) profile. The outbreak itself is
      always associated with the initial contamination of a RTE ("ready to eat")
      product and re-contamination by inappropriate handling after cooking.
      Consequently, in most cases the RTE product is subject to inadequate
      refrigeration during an excessive shelf-life. The responsibility of the food
      industry and the consumer is clearly engaged during this scenario of foodborne
      diseases. The question is how to avoid the introduction of this particular strain
      of L. monocytogenes in the food chain. In a study we tried to evaluate the risk
      of pig carcass contamination at slaughterhouse level and to identify the main
      risk factors associated with the infection of live pigs. In most cases
      inappropriate cleaning and disinfection of surfaces were associated with the
      contamination of raw meat, but in some cases the introduction of epidemic strains
      in the food chain was also associated with primary production. Feeding with soup
      in piggeries seemed to select a particular microbial ecology associated to L.
      monocytogenes contamination of live pigs. The possible strategies that may be
      used to control L. monocytogenes in live pig production are not yet developed
      sufficiently to be included in the EC regulation but should be discussed in more
      detail.

PMID- 15469064
TI  - [Noroviruses and sapoviruses in man and farm animals].
AB  - Noro- and Sapoviruses belong to the virus family Caliciviridae and are important
      causative agents of acute epidemic gastroenteritis in man. In many cases
      transmission of Noro- and Sapoviruses occurs via contaminated food or water and
      the respective diseases are therefore designated as food borne. Recently, the
      presence of Noro- and Sapoviruses in farm animals has attracted increasing
      attention. Clinical symptoms were observed after experimental infection of cattle
      and swine with members of the two virus groups. Thus far it is not known, whether
      virus transmission from animals to man does occur.

PMID- 15469065
TI  - [Hepatitis C virus. Iatrogenic and nosocomial transmition?].
AB  - The hepatitis C virus (HCV) infection constitutes an important, worldwide public
      health problem. Studies about the prevalence of HCV antibodies among surgical
      patients are few, and the involvement of surgery in the iatrogenic transmission
      of HCV remains a matter of controversy. Blood transfusions and other medical
      acts, have contributed to the spreading of HCV among the population. However,
      some HCV patients do not have antecedents of transfusions which suggest other
      mechanisms of transmission such as surgical acts, that continue facilitating the
      viral transmission. Some studies find an association between previous
      hospitalizations and the HCV infection, others report that such association does
      not exist. Several investigations suggest that the HCV infection risk does not
      reside in the surgery, but in the use of multidose containers, anesthetic
      products, saline solution, etc., administered during surgery. In Venezuela, the
      HCV overall prevalence is 1%. However, in poli-transfused, hemodialized or
      surgical patients is 10-22%. The studies carried out in surgery units, support
      the idea that surgical acts are not involved in the HCV spreading, although they
      can be responsible for this transmission in specific occasions. The HCV
      transmission due to surgical acts can happen in particular contexts of the
      sanitary environment and the study of this relationship is essential to adopt
      preventive measures that can help to eradicate or decrease this problem.

PMID- 15469066
TI  - [Chromosome alterations in workers exposed to ionizing radiation].
AB  - With the purpose of determining and characterizing chromosomal alterations and
      their relation to the radiation dose, time of employment and weekly exposure
      time, a transversal cut-descriptive study was performed on 18 workers, exposed to
      ionizing radiation, from a specialized company in the Venezuelan oil industry.
      These workers, male and females, constituted all the population studied, aged
      between 32 and 59 years, with at least one year on the job. A random sample of a
      non-exposed group of workers was used as a control. An occupational medical
      report was applied and personal dosimetry, environmental monitoring and a
      chromosomal analysis using two chromosomic culture techniques, were performed.
      The results show, in the exposed groups, an age average of 46.10 +/- 7.69 years,
      an average 17.5 +/- 5.00 years of employment and a weekly exposure of 4.30 +/-
      1.33 hours. In the exposed population, 444 chromosomal abnormalities were
      evidenced in 700 metaphases studied; these abnormalities consisted of 66.6%
      single fragilities, 22% of combined fragilities, with chromosomic ruptures,
      deletions and poliploids, and 11% presented a normal kariotype. The control group
      presented chromosomic alterations as single fragilities in 55% of the cases.
      Radiologists presented 88.8% of chromosomic alterations, with below permissible
      doses detected, and 11.2% of them with exceed doses, presented the greatest
      number of fragilities and multiple chromosomic ruptures. The radiologists with
      weekly exposures of 8 hours presented the highest number of chromosomic
      alterations. 88% of radiologists with chromosomal abnormalities had more than 10
      years of exposure. In conclusion, chronic exposure to low levels of ionizing
      radiation can induce chromosomic alterations, depending on the years of
      employment and the weekly time of exposure.

PMID- 15469067
TI  - [Evaluation of the inmunohistochemical markers PCNA and MIB-1 in the diagnosis of
      low grade lesions of the uterine cervix].
AB  - A prospective and comparative study of 112 uterine cervix biopsies, received from
      hospitals of Maracaibo, Venezuela, with the diagnosis of cervical intraepithelial
      neoplasia I (CIN I) determined with the traditional Hematoxilin-Eosin (H-E)
      diagnostic staining, was performed to compare the inmunohistochemical markers
      PCNA and MIB-1 with the conventional H-E staining. The samples were classified
      with H-E, and 3 samples were excluded of the study with a different diagnostic
      from CIN I. After the inmunohistochemical study, 19 biopsies (17.4%) were
      classified as CIN II with PCNA and 18 (16.5%) with MIB-1. The analysis showed a
      significant difference (p < 0.01) between the H-E staining and the inmunomarkers.
      These results allow us to conclude that the inmunohistochemical evaluation of the
      proliferative activity is very useful to establish with certainty the diagnosis
      of preneoplasie lesions of uterine cervix and also represents and important
      parameter in the prognostic evaluation.

PMID- 15469068
TI  - [Preliminary evaluation of a rapid, qualitative one step immunoassay of cardiac
      Troponin I in the acute myocardial infarction diagnosis].
AB  - The cardiac Troponin I is considered the biochemical marker of election to detect
      acute myocardial infarction, a medical urgency that requires a rapid diagnosis.
      In this article, the diagnosis of this condition was studied qualitatively
      through an immunochromatographic assay of a single step detection of cardiac
      Troponin I elaborated in the laboratory comparing it with another, commercially
      available, qualitative immunochromatographic assay of detection of cardiac
      Troponin I, Cardiac STATUS TM. The plasmas of 76 patients with acute myocardial
      infarction and 50 plasmas obtained from healthy donors were evaluated
      retrospectively. The laboratory's immunoassay did not present cross reactivity
      with the skeletal isoform of Troponin I. This test detected 1 ng/mL or more of
      cardiac Troponin I in the form of a tertiary complex in plasma and it also
      recognized the free molecule. The clinical sensitivity of the immunoassay of the
      laboratory in patients with Q wave type acute myocardial infarction was 100% and
      for the commercial immunoassay was 85.7% in the period of 6 h to 24 h following
      the onset of chest pain. For this type of infarction, the signal was detected up
      to 148 h after the onset of symptoms and the clinical sensitivity oscillated
      between 84.2% and 90.9% for both assays. The clinical sensitivities of the two
      immunoassays were 70% in the case of patients with non-Q wave acute myocardial
      infarction. With healthy donor's samples, the clinical specificity of the
      immunochromatographic assay prepared in the laboratory was of 90.4% and for
      commercial immunoassay was 100%. The immunochromatographic immunoassays of a
      single step for the detection of cardiac Troponin I evaluated in this work,
      diagnosed in a quick and easy way, important myocardial cell death and to lesser
      extent smaller necrosis, in patients without concluding electrocardioghraphic
      signs and with the possibility of the occurrence of complications.

PMID- 15469069
TI  - [Serum values of cytokines in children with vitamin A deficiency disorders].
AB  - Vitamin A Deficiency Disorders (VADD) have been associated with alterations of
      cellular differentiation, regulatory functions of the immune system and increased
      children morbidity and mortality rates due to acute respiratory and intestinal
      infections. The aim of the present study was to determine serum concentrations of
      Thl-Th2 cytokines in VADD children. The sample consisted of 138 children (F=72;
      M=66; 4-7 y old) living in slums in Maracaibo, Venezuela, with an adequate
      nutrition assessed by clinics and anthropometry. Vitamin A status was assessed by
      the Conjunctival Impression Cytology (CIC) technique following the ICEPO
      methodology, which determines Normal CIC = control or Abnormal CIC = VADD. The
      cytokines IL-10, IL-4 and IFN-gamma (pg/mL) were analyzed by the ELISA method;
      and IL-2 (U/mL) by the EAISA method. The Student's t test was applied to detect
      differences between values (p<0.05). No one child presented clinical evidence of
      VADD; 71 children (51.40%) exhibited normal CIC (control), whereas 67 children
      (48.60%) presented abnormal CIC indicative of sub-clinical manifestation of VADD.
      The prevalence was higher, although non significant, in females, 5-6 y old
      children and amerindians (51.39%, 64.18% and 60.40%, respectively). A diminished
      serum concentration of IL-10 was detected in VADD children, in comparison with
      the control group (4.41 +/- 1.27 pg/mL vs. 6.03 +/- 3.90 pg/mL) (p<0.03). The
      rest of studied cytokines were not significantly different with respect to
      control. The IL-10 diminution in VADD children would be related to the alteration
      of the inflammatory response at the level of respiratory and intestinal epithelia
      affected by infections.

PMID- 15469070
TI  - [Attitude of hemophilic adult individuals towards their disease].
AB  - The mental health of hemophilic individuals and their families play an important
      role on the integral treatment of the disease. The knowledge of the beliefs and
      attitudes perceived by the patients toward their disease will make possible a
      positive influence in their clinical improvement, their response to the
      treatment, as well as their quality of life. On the basis of the Azjen and
      Fishbein's Theory of Reasoned Action, a questionnaire was applied to 43 adult
      hemophilics to determine the salient beliefs about their disease. These beliefs
      permitted to elaborate a main structured questionnaire named Attitude Model in
      Patients with Hemophilia (Modelo de Actitud en Pacientes con Hemofilia, MAPACHE,
      in spanish), which was administered to the individuals and thus, the attitude
      toward their disease was obtained. Seventy two percent (72%) gave a major
      importance to the clinical aspects of the disease (hemorrhage, joint discomfort
      and trauma), 40% knew the general concepts of hemophilia (heredity, care and
      seriousness of the disease), 20% mentioned the implications of the psychosocial
      factors and only 18% had knowledge concerning the coagulation factors deficiency
      and the appropriate treatment. The MAPACHE showed a slightly positive score
      attitude (4.44 +/- 1.12 SEM) towards the disease in the majority of the groups
      (74.5%); with 26% of the hemophilics with a negative attitude. There were no
      significant differences between attitude and clinical parameters. It is
      recommended that a multidisciplinary team of caregivers should focus their
      efforts toward education and preventive measures in order to avoid the
      complications and consequences of the disease, to make possible a better quality
      of life in individuals with hemophilia.

PMID- 15469071
TI  - Pancreatic toxicity in mice elicited by Tityus zulianus and Tityus discrepans
      scorpion venoms.
AB  - Envenoming by Tityus discrepans (TD) scorpions in northcentral Venezuela mainly
      causes pancreatic and gastrointestinal complications whereas the sting by Tityus
      zulianus (TZ) (western Venezuela) often produces respiratory arrest and death by
      pulmonary oedema. Since TZ pancreatic toxicity may have been overlooked, a study
      was carried out to evaluate TZ venom effect on mice pancreas. BALB/c mice were
      injected intraperitoneally with 0.5 mg protein/kg of either TD or TZ venoms. A
      significant increase in serum-amylase activity (IU/mL) was obtained after 3 h
      (20.6 +/- 3.0, p < 0.05) and 6 h (60.4 +/- 3.0, p < 0.001) of TZ venom injection
      compared to saline-inoculated mice. Increased amylase levels were also elicited
      by TD venom, although these were significantly lower than those induced by TZ.
      Light microscopy of pancreas from TZ-envenomed mice revealed interstitial oedema
      and vacuolization of acinar cells as soon as 1 h after injection. Differences in
      the time course of the pancreatic oedema (wet pancreas weight/body weight ratio)
      elicited by TD and TZ venoms suggest the existence of species-specific mechanisms
      for oedema formation. Taken together, these data suggest that the TZ venom
      contains components highly toxic to the mammalian pancreas, which may play a role
      in developing TZ-related pulmonary complications.

PMID- 15469072
TI  - Central nervous system paracoccidioidomycosis: case report and review.
AB  - Paracoccidioidomycosis is a systemic infection caused by a dimorphic fungus
      (Paracoccidioides brasiliensis). The most common lesions frequently occur in the
      bucopharinx mucosa. Other lesions occur in the adrenal glands, liver, bone,
      gastrointestinal tract, lungs and nervous system. We report here a case of
      neuroparacoccidioidomycosis. The patient was a 49 year-old male, who consulted
      due to neurological symptoms (cephalalgia, speech difficulty and one tonic clonic
      seizure with urinary incontinence) of eight months duration. Upon physical
      examination it was observed an emaciated male with nail clubbing, a skin ulcer
      with raised edges and a crusted bottom of 4 x 2 cm in diameter located in the
      right supraclavicular region and an ulcerated lesion in the left tonsil with
      edema. The rest of the physical examination reveled a discrete left side
      hemiparesis and pulmonary rales in the left hemitorax. The fungus was identified
      through direct examination of cerebrospinal fluid (CSF). The histopathology of
      suprarenal, lungs, brain and skin showed multiple paracoccidioidal granulomas. To
      the best of our knowledge, this is the third case reported in the literature. We
      review the literature on the pathogenesis and prevalence of
      neuroparacoccidioidomycosis.

PMID- 15469073
TI  - [Endoscopic guided nasal and skull base operation].

PMID- 15469074
TI  - [Expression and correlation of apoptosis-related gene c-IAP2 and caspase-4 in
      sinonasal squamous carcinoma].
AB  - OBJECTIVE: To examine the expression of apoptosis-related genes c-IAP2 and
      caspase-4 in sinonasal squamous carcinoma. To investigate the role and mechanism
      of the two apoptosis-related genes in nasal cavity and sinus squamons carcinoma.
      METHODS: Forty-one pathologically confirmed specimens of nasal cavity and sinus
      squamons carcinoma were subjected for immunohistochemical staining to analyze the
      expression of c-IAP2 and caspase-4, in addition 10 normal nasal mucosa were used
      as control. RESULTS: The positive rate of c-IAP2 in sinonasal squamons carcinoma
      was 87.8%, among which 14 cases were strongly stained(+ + +), 15 cases were
      stained(+ +), 7 cases were stained (+), only 5 cases were negative. In 10 normal
      control tissues, no case was stained(+ + +), 2 cases were stained (+ +), 3 cases
      were stained(+), the other 5 cases were negative. Higher level expression of c
      IAP2 protein was detected more often in squamons carcinoma specimens than that in
      normal nasal mucosa. There was statistically significant difference between the
      two groups for the staining(P < 0.05). The expression of c-IAP2 was not
      correlated with clinical staging (P > 0.05), but there were positive correlation
      with clinical prognosis (P < 0.01) and pathological classification (P < 0.01);
      The positive rate of caspase-4 in nasal cavity and sinus squamons carcinoma was
      58.5%, among which 4 cases were strongly stained (+ + +), 7 cases were stained (+
      +), 13 case was stained(+), 17 cases were negative. The expression of caspase-4
      protein was more deletion in squamons carcinoma specimens than that in control
      group, there was statistically significant difference between the two groups for
      the staining (P < 0.05). The expression of caspase-4 protein was negatively
      correlated with clinical prognosis (P < 0.01) and pathological classification ( P
      < 0.01), not correlated with clinical staging(P > 0.05). The expression of c-IAP2
      was negativelly correlated with the experssion of caspase-4. CONCLUSIONS: The
      results indicates that in sinonasal squamous carcinoma, c-IAP2 is activated,
      while caspase-4 is restrained, the signal transduction pathway of apoptosis is
      arrested, leading to surviving of tumor cells, this maybe directly associated
      with the development of sinonasal squamons carcinoma, and with the failure of
      tumor trentment.

PMID- 15469075
TI  - [Clinical analysis of 34 cases of esthesioneuroblastoma].
AB  - OBJECTIVE: To study the diagnosis, treatment policy and prognosis in patients
      with esthesioneuroblastoma. METHODS: A retrospective review was conducted in 34
      patients treated at Cancer Hospital of CAMS from 1958 to 1998. According to the
      Kadish system, the patients were staged as follows: stage A, 1 case; stage B, 9
      cases; and stage C, 24 cases. Three patients were treated with surgery alone, 9
      irradiation alone, and 15 combination with surgery and radiation, 4 combination
      with radiation and chemotherapy and 3 surgery, radiation and chemotherapy.
      RESULTS: The overall 5-year survival rate was 47.1% (16/34). The survival rates
      for stag A, B, and C were 100% (1/1), 88.9% (8/9), and 29.2% (7/24) respectively.
      The survival rates for surgery alone, radiation alone and combined therapy were
      33.3% (1/3), 33.3% (3/9), and 54.5% (7/24), respectively. The local control rate
      and distant metastasis rate were 61.8% (21/34) and 32.4% (11/34), respectively.
      There were 10 patients died of distant metastasis and 5 patients died of local
      recurrence. The survival rate in patients with early stage (A + B)
      esthesioneuroblastoma was significantly better than that in patients with
      advanced stage (C) (chi2 = 8. 174, P = 0.004). The young patients (< or = 30
      years) had a remarkable higher distant metastasis rate (chi2 = 3.865, P = 0.049)
      and poor prognosis (chi2 = 4.194, P = 0.041) than elder patients. CONCLUSIONS:
      Early detection and combined therapy were important to improve survival rate. The
      combined therapy with preoperative radiation therapy and surgery could help to
      achieve excellent local control. Distant metastasis was an important factor which
      affected the prognosis of the patients.

PMID- 15469076
TI  - [Rescue operations of the recurrent nasal and paranasal sinus neoplasms].
AB  - OBJECTIVE: To investigate the symptoms, factors relating to recurrences, the
      styles of the rescue operation and the reconstructive methods of the surgical
      defects in patients with recurrent nasal and paranasal sinus neoplasms. METHODS:
      Excluding the primary neoplasm, only patients with recurrent tumors and suitable
      for rescue operations entered the group. Kaplan-Meier method was used to estimate
      the survival probability. RESULTS: Twenty-five patients receiving rescue
      operations from 1993 to 2002 who met the above inclusion criteria were reviewed.
      The age ranged from 13 - 66 years. All the patients had once surgery or radiation
      therapy at least. The time between the last treatments and the recurrences ranged
      from 2 weeks to 46 months. 80 per cent of the recurrences were within the first 2
      years after the last therapy. The recurrent symptoms included headache (10
      patients), eminences in or around the operation fields (9 patients), diminution
      of vision (7 patients), and so on. The patients were followed 1 to 65 months.
      There were no patients died during the rescue operations. Five patients were
      alive without recurrences and 3 alive with local or regional recurrences.
      Thirteen died of local recurrences and 1 died of metastasis to lung. The one
      year, 2-year and 3-year survival rate were 62.5%, 43.7% and 29.1%, respectively.
      The median survival time was 18 months. Complications included cerebrospinal
      rhinorrhea (3 patients), central diabetes insipidus (1 patient) and necrosis of
      part of the flap (1 patient). CONCLUSIONS: Most of the local recurrences occur
      within 2 years after the last therapies. The recurrent symptoms are commonly
      headache and eminences in or around the operation fields. The recurrences are
      closely related to pathological types and differential degrees of the neoplasms.
      The reasonable and timely combined treatment may help to decrease the frequencies
      of the recurrences. The rescue operations with effective methods can improved the
      patients' life qualities and lengthen their life spans. The main complications
      are cerebrospinal rhinorrhea most of which can be cured by conservative
      treatment.

PMID- 15469077
TI  - [Analysis of 60 masses in the nasal vestibule].
AB  - OBJECTIVE: To summarize the treatment strategy of nasal vestibule masses.
      METHODS: Between May, 1982 and April,2003,60 patients with nasal vestibule mass
      were treated in our department. The clinical features of these masses were
      retrospectively analysed. RESULTS: Among 60 masses, 51 cases were benign tumors,
      5 cases were inflammatory masses, and 4 cases were malignant tumors. All patients
      were surgically treated and discharged with complete recovery. Among patients
      with benign tumor and non-specific inflammatory mass, 37 patients with a median
      follow-up of 97 months without recurrence and malignant change. One patient with
      hidradenoma and one patient with rhinoscleroma recurred and another surgery was
      carried out. There was no recurrence after second surgery. 6 patients died of
      other diseases, and 11 patients lost follow-up. Two patients with malignant
      melanoma recurred after first surgery. Then the tumor was removed via lateral
      rhinotomy and died of local recurrence and liver metastasis. Two patients (one
      with papilloma carcinomatous change and another with non-Hodgkin lymphoma) were
      free of diseases 17 years or 5 years and 2 months respectively. CONCLUSIONS:
      Masses of different histological types can be found in the nasal vestibule.
      Surgical removal is the treatment of choice. The approaches are determined on the
      basis of site, size and kind of the masses.

PMID- 15469078
TI  - [Repair of the rabbit ear cartilage defects with transforming growth factor-beta1
      and allogenic chondrocyte/poly-DL-lactide higher porosity polymer].
AB  - OBJECTIVE: To study the repair of the rabbit ear cartilage defects with
      transforming growth factor-beta1 (TGF-beta1) and allogenic chondrocyte/poly-DL
      lactide (PDLLA) higher porosity polymer. METHODS: A total of 18 rabbits were
      divided into the TGF-beta1 and chondrocytes/PDLLA graft group, the
      chondrocytes/PDLLA graft group, and the blank control group. Samples were taken
      out at 4, 12 and 18 weeks after implantation. The histological characteristics
      were investigated. RESULTS: After 18 weeks of the transplantation, the repaired
      effects of TGF-beta1 and allogenic chondrocytes/PDLLA graft group was better than
      the allogenic chondrocytes/PDLLA graft group not only on general sample but also
      histology, and the blank control group were repaired with fibrous tissue.
      CONCLUSIONS: The allogenic chondrocytes/PDLLA graft could repair the rabbit ear
      cartilage defects while TGF-beta1 could improve the quality of the rabbit ear
      cartilage defects.

PMID- 15469079
TI  - [Study of the relation between Cx31 gene and hereditary hearing impairment].
AB  - OBJECTIVE: To study the relation between hereditary nonsyndromic hearing
      impairment (NSHI) in Chinese and mutation in Connexin 31 (Cx31) gene and to
      explore the pathogenic mechanism. METHODS: Forty-seven pedigrees with hereditary
      NSHI, 38 Children with sporadic NSHI and cases of control were collected in
      present studies. The coding sequence of Cx31 gene was amplified by polymerase
      chain reaction (PCR), screened by denaturing high-performance liquid
      chromatography (DHPLC) and confirmed by direct sequencing. RESULTS: The mutation
      rate of heterozygous mutation C --> T at position 798 of Cx31 cDNA in patient
      group and in control were 14.1% (12/85) and 1% (1/100) respectively. Significant
      difference was found between the two group (P < 0.01). Heterozygous mutation G -
      > A at position 580 of GJB3 cDNA, which results in a missense mutation (A194T),
      was found in two members of one pedigree with autosomal dominant NSHI. The
      mutation was not found in numbers with normal hearing of this pedigree and
      controls. Heterozygous mutation G --> A at position 250 of Cx31 cDNA was found in
      one child with sporadic congenital NSHI. In our previous studies, Cx26 gene
      mutations have been screened among the patient with hereditary NSHI and sporadic
      NSHI and the control of our test, and two Cx26 gene mutations were found in two
      pedigrees. But the two NSHI pedigrees which were confirmed to have Cx26 gene
      mutation were not found to have Cx31 mutation. The patient and the control which
      were confirmed to have Cx31 gene mutations were not found to have Cx26 mutations.
      CONCLUSIONS: Cx31 gene was associated with nonsyndromic hearing impairment There
      was no cross and cooperative effect between Cx26 gene and Cx31 gene.

PMID- 15469081
TI  - [The influence of protein kinase C inhibitor in eosinophil apoptosis of nasal
      polyps].
AB  - OBJECTIVE: To study the influence of the inhibitor of protein kinase C (PKC), Iso
      H7 [1-(5-lsoquinolinyl-sulfony)-3-methylpiperazine dihydrochloride] on eosinophil
      apoptosis in nasal polyp tissues. METHODS: Nasal polyp tissues were cultured and
      divided into two groups, test group (with Iso-H7 in different concentration) and
      control group (without the inhibitor of PKC), to check out the influence of Iso
      H7 on eosinophil apoptosis in nasal polyps. The nasal polyp tissues were cultured
      in Iso-H7 in concentration of 10(-6), 10(-4), 10(-2) mol/L for 1 d, 3 d, and 5 d,
      respectively. Eosinophil apoptosis index was measured with TUNEL (terminal
      deoxynucleotidyl transferase d-UTP nick end labeling), in situ hybridization and
      MGG staining to identify eosinophil apoptosis. RESULTS: Occasionally, there was
      little eosinophil apoptosis in two groups in 1 d, but in 3 d, There were a great
      deal of eosinophil apoptosis in test group. The eosinophil apoptosis indexs of
      the two groups were significantly different (P < 0.01). The indexs of eosinophil
      apoptosis was not significantly higher in 3 d than that in 5 d in test groups (P
      > 0. 05), but significantly higher than that in 1d (P < 0. 01). CONCLUSIONS: Iso
      H7 takes a important role in accelerating eosinophil apoptosis. The inhibitor of
      PKC could significantly promote eosinophil apoptosis in nasal polyps. There is no
      dosage and time dependence of PKC inhibitor in regulating eosinophil apoptosis of
      nasal polyps.

PMID- 15469080
TI  - [Computer-assisted anatomical study of nasofrontal region].
AB  - OBJECTIVE: To evaluate the value of Advantage Windows 3.1 (AW 3.1) software for
      anatomical study of nasofrontal region, and to study the CT characteristics of
      nasofrontal region which related to the frontal sinus surgery. METHODS: Eighty
      patients underwent axial consecutive computed tomography scans and these data
      were studied with AW 3.1 software which provided reconstructional imaging of
      continuous coronal, sagittal, axial sections. Some related structures of
      nasofrontal region were studied and measured. RESULTS: AW 3.1 software could
      identify and measure the following structures accurately: The diameter of frontal
      sinus was (22.5 +/- 8.6) mm in height, (16.3 +/- 6.8) mm in depth, (23.8 +/- 9.8)
      mm in breadth. The diameter of frontal sinus ostium: the anterior-posterior
      diameter was (7.3 +/- 1.7) mm, the transverse diameter was (8.5 +/- 1.9) mm. The
      width of nasal beak of frontal bone(5.9 +/- 1.4 ) mm. The distance of frontal
      sinus ostium to the floor of columella nasi and the corresponding angle to the
      nasal floor were (60.8 +/- 4.2) mm and (70.1 +/- 4.7) degrees. The superior
      attachment sites of the uncinate process were as follows: lamina papyracea 41%,
      posteromedial wall of agger nasi cell 11%, middle turbinate 19%, anterior skull
      base 16%, superior bifurcation 13%. The cells could impinge on the frontal recess
      to cause obstruction (terminal recess 38.8%, anterior ethmoid cell 27.6%, agger
      nasi cells 24.5%). The accessory cells could impinge on the frontal sinus
      (perifrontal cells 32.7%, superaorbital cells 38.8%, intersinus septal cells
      32.0%). There was significant difference between two groups of characteristics of
      nasofrontal region. CONCLUSIONS: AW 3.1 software is a helpful and powerful new
      tool for anatomical study of nasofrontal region and for preoperative evaluation.
      The structures of nasofrontal region are complex and various, frontal sinusitis
      almost always results from the obstruction of frontal sinus outflow tract. These
      results of anatomical study of nasofrontal region are helpful in directing the
      functional endoscopic surgery in frontal sinus.

PMID- 15469083
TI  - [Evaluation of sentinel lymph node in squamous cell carcinoma of the head and
      neck].
AB  - OBJECTIVE: To assess the feasibility of sentinel lymph node (SLN)
      radiolocalization in stage in head and neck squamous cell carcinoma and to gain
      insight as to whether the sentinel lymph node could be prognostic of regional
      micrometastatic disease. METHODS: A prospective trial was made on the application
      sentinel lymph node radiolocalization in 10 patients with NO squamous cell
      carcinoma of the head and neck region. For each patient a peritumoral submucosal
      injection of filtered technetium 99m prepared with dextran colloid (99mTc-DX) was
      performed immediately. After 30 minutes, focal areas of accumulation
      corresponding to sentinel lymph nodes (SLN) were marked on the skin surface. The
      SLN was localized by lymphoscintigraphy and intraoperatively through the intact
      skin by a hand-held gamma-probe. SLN was defined as the count of lymph node could
      be detected 4 times more than that of background. Complete neck dissections were
      performed, and SLNs were identified for later histological evaluation and
      comparison to the remaining lymphadenectomy specimen. RESULTS: SLN
      radiolocalization accurately identified one or more SLNs in the ten cases. 3 of
      10 cases revealed occult metastatic disease. Therefore the negative metastasis
      rate was 30% (3/10). The positive rate of SLN and nonsentinel lymph node (NSLN)
      were 22.7% (5/22) and 0.4% (1/247) respectively. Serial sectioning (SS) and
      immunohistochemical (IHC) on SLNs would reduce the false-negative rate of
      sentinel lymph node biopsy (SLNB). There was no instance in which SLN was
      negative for micrometastatic disease while being positive in a nonsentinel lymph
      node. CONCLUSIONS: SLN evaluation in NO neck in squamous cell carcinoma of the
      head and neck is accurately feasible and seems to adequately predict the presence
      of occult metastasis. Although SLN radiolocalization in head and neck squamous
      cell carcinoma may potentially reduce the time, cost, and morbidity of regional
      lymph node management, more experience with technique is required before its role
      can be determined.

PMID- 15469082
TI  - [Expression of survivin gene and its relationship with expression of p15, p16
      proteins in laryngeal squamous cell carcinomas].
AB  - OBJECTIVE: : To investigate the expression of Survivin (SVV) and its relationship
      with expression of p15, p16 in laryngeal squamous cell carcinoma (LSCC). METHODS:
      Using strep avidin-biotin complex (SABC) method, we examined the expression of
      SVV, p15 and p16 gene in 48 LSCC tissus samples, 24 normal laryngeal mucosa
      tissus samples and 24 normal laryngeal tissus adjacent to the tumors samples.
      RESULTS: SVV was expression in 27 of 48 (56.3%) samples of LSCC and expression in
      6 of 24 (25.0%) samples of normal laryngeal tissus adjacent to the tumors. Normal
      laryngeal mocosa tissus samples did not expressed SVV. Overexpression of SVV was
      related to the tumor site, grade, clinical stage and tumor prognosis (P < 0.05).
      The expression of SVV in LSCC was positive correlated with p16 expression( C =
      0.52 P < 0.001), but not with p15 expression. CONCLUSION: SVV may play a role in
      the pathway of carcinogenesis and tumor progress. It is feasible for early
      diagnosis and prognosis estimation. Overexpression of SVV gene and de-activation
      of antioncogene p16 may be play synergetic roles in the carcinogenesis of LSCC.

PMID- 15469084
TI  - [Investigation and analysis of quality of life for patients after laryngectomy].
AB  - OBJECTIVE: To institute and test the quality of life for laryngectomy, and
      evaluate the feasibility of above questionnaire in patients after laryngectomy.
      METHODS: A questionnaire of quality of life for laryngectomy was instituted. An
      investigation was conducted in patients treated by partial (36, Group A) or total
      (45, Group B) laryngectomy for laryngeal cancer with above questionnaire. The
      feasibility, reliability and validity of the questionnaire was evaluated, the
      quality of life and the influencing factors in laryngectomy were also analyzed.
      RESULTS: The questionnaire of quality of life for laryngectomy consists of 22
      items, covering six aspects. The questionnaire has a comparatively good
      reliability, and the criterion-related validity and content validity of the
      questionnaire is valid. The correlation coefficient of split-half method and
      Cronback's alpha of questionnaire were 0.842 and 0.889 respectively. The
      composite quality of life scores of group A were significant higher than those of
      group B ( P < 0.001). The differences in physical function, laryngeal function,
      psychological state, the ability of living independently were statistically
      significant (P < 0.001; P < 0.001; P < 0.01; P < 0.05) as well. Seven factors
      including operative modality, tumor stage, postoperative complication, coexisted
      disease, family incomes, voicing modality and wearing tracheo-cannula were
      related to postlaryngectomy quality of life. CONCLUSIONS: The questionnaire of
      quality of life for laryngectomy has speciality in laryngectomy and a
      comparatively good reliability and validity, and it is suitable for quality of
      life research in patients after laryngectomy.

PMID- 15469085
TI  - [Visualization and thin sectional anatomy of the laryngeal cartilages].
AB  - OBJECTIVE: To establish digitized visible model of the laryngeal cartilages of
      the visible human, providing morphological data for image diagnosis and
      laryngectomy. METHODS: Cross-sectional images of fresh tissues from the Chinese
      visible human data set were reviewed, and the laryngeal cartilages structures
      data were used, the data was on a section-by-section basis. Three-dimensional
      computer reconstructions of the laryngeal cartilages were generated from these
      data by surface rendering on a SGI workstation. RESULTS: The digital images from
      the visible human offer unique insights into the complex anatomy and ossification
      of the laryngeal cartilages, the quality of the computerized 3D-reconstructed
      images was distinct and perfect. CONCLUSIONS: The visible human data set can
      provide complete and accurate data The digitized model of the laryngeal
      cartilages offer unique insights into the laryngeal anatomy, could be used for
      resident education, rehearsal of an unfamiliar surgery and for developing a new
      surgical approach.

PMID- 15469087
TI  - [Free radical homeostasis].
AB  - Although free radicals have reactive chemical properties, the characteristics of
      free radical homeostasis have been maintained during the evolution of oxygen
      requiring organisms. These characteristics are implicated in performing diverse
      physiological functions and none of deleterious effects resulting from neat
      balance of production and scavenging of free radicals, as well as the repair of
      radical-induced damage of bio-macromolecules under physiological conditions.
      Nutrients and their metabolites along with "essential" antioxidants play crucial
      roles in maintaining free radical homeostasis. Glutathione homeostasis
      interrelates synergistically with free radical homeostasis. Free radical
      homeostasis should be maintained well in healthy humans at different ages and
      under various living conditions in order that oxidative stress and its induced
      oxidative damage will be prevented or ameliorated before aging.

PMID- 15469088
TI  - [Progress on embryonic stem cells for the treatment of myocardial infarction].
AB  - Embryonic stem cells are pluripotent cells derived from blastocyst-stage embryos.
      They are characterized by their capacity for self-renewal and by the ability to
      differentiate into a variety of cell types. In vitro, ES cells can spontaneously
      aggregate into the formation of embryoid bodies (EBs) comprised of a range of
      differentiated cells. When injected into severe combined immunodeficient (SCID)
      mice, ES cells will induce the generation of teratomas, which include
      differentiated cells from three embryonic germ layers. We can induce the
      differentiation of ES cells into cardiocytes by treatment with several growth
      factors or co-culture with certain other cells. The pure differentiated
      cardiocytes from ES cells are then selected and implanted into the infarcted
      hearts. The hearts' function will be improved. ES cells implantation is a novel
      and potential method to treat infarcted hearts.

PMID- 15469089
TI  - [Advances in study on molecular mechanism of circadian clock in pineal gland].
AB  - The pineal gland functions as a central circadian oscillator in a variety of
      nonmammalian vertebrates. More recently, clock genes such as Per, Cry, Clock, and
      Bmal have been found in a variety of vertebrate clock structures including the
      avian pineal gland. The profiles of the temporal change of the clock gene
      expression in the avian pineal gland are more similar to those in the mammalian
      suprachiasmatic nucleus (SCN) of the hypothalamus. Avian pineal gland and
      mammalian SCN seem to share a fundamental molecular framework of the clock
      oscillator composed of a transcription/translation-based autoregulatory feedback
      loop. Some products of the clock genes serve as positive or negative regulators
      influencing the clock oscillation. The circadian time-keeping mechanism is also
      involved in several post-translational events. The above-mentioned processes play
      a quite important role in the stability of the oscillator and/or the photic-input
      pathway for entrainment of the clock.

PMID- 15469090
TI  - [Signal transduction pathways and transcription factors involved in luteinizing
      hormone beta subunit gene expression].
AB  - The pulsatile pattern of the hypothalamic hormone gonadotropin-releasing hormone
      (GnRH) plays a critical role in reproductive function by regulating the
      biosynthesis and secretion of the pituitary gonadotropins. Follicle-stimulating
      hormone (FSH) and Luteinizing hormone (LH) are heterodimeric glycoproteins
      composed of a common peptide, the glycoprotein hormone subuint alpha, and either
      a specific FSHbeta or LHbeta polypeptide. GnRH regulates LHbeta gene expression
      through GnRH receptor activation of the protein kinase C (PKC) and calcium
      signaling cascades. Recently, many transcription factors, such as early growth
      response-1 (Egr-1), steroidogenic factor-1 (SF-1), Ptx1 and Sp1, have been
      recognized to be involved in expression of the LHbeta gene through binding to the
      promoter region of LHbeta gene.

PMID- 15469091
TI  - [Signal transduction on transdifferentiation of renal tubular epithelial cell].
AB  - It is an important cell biological phenomenon that epithelial cells transit into
      mesenchymal cells under special physiological and pathological condition. In
      recent years, it has been known that epithelial-mesenchymal-transition may be
      mediated by several intracellular signaling pathways, such as MAPK, Rho, Src, PI3
      kinase and Smads. Renal tubular epithelial cells have been observed to transit to
      myo-fibroblasts in renal diseases. However, the intracellular signaling pathways
      are rarely known. The progress on this field is reviewed.

PMID- 15469092
TI  - [Progress in the basic research on neurobiological mechanisms of cancer pain].
AB  - Pain shows the most disruptive influence on the quality of the life of cancer
      patients. However, the basic neurobiology of cancer pain is poorly understood, as
      no appropriate animal model of cancer pain is available. New insights into these
      mechanisms are now arising from femur, calcaneus, humerus model of cancer pain in
      murine and tibia model in rats. Cancer pain has its unique mechanisms such as
      osteolysis, peripheral sensitization, central sensitization and nerve entrapping,
      which are all involved in the development and maintenance of cancer pain. Here we
      summarized the study progress of cancer pain animal models, neurochemical
      mechanisms and drugs for treatment of cancer pain from recent literatures.

PMID- 15469094
TI  - [Current progress of a novel oxygen-binding protein: neuroglobin].

PMID- 15469093
TI  - [Myocardin: a novel regulator of muscle-specific gene expression].

PMID- 15469095
TI  - [Applications of proteomic approach in studying cardiovascular diseases].

PMID- 15469096
TI  - [Progress in the study of centrins, a centrosome protein].

PMID- 15469097
TI  - [Progress of research on stem cell plasticity].

PMID- 15469098
TI  - [14-3-3: protective regulatory protein in signaling transduction].

PMID- 15469099
TI  - [Some progress about channelopathies].

PMID- 15469100
TI  - [Progress of investigation on volume-regluated anion channels].

PMID- 15469101
TI  - [Protein local synthesis in neuronal processes].

PMID- 15469102
TI  - [The effect of BMP family and its receptors on animal reproduction].

PMID- 15469103
TI  - ["Oddball" paradigm and P300].

PMID- 15469104
TI  - [The role of osteoclasts on the bone destruction of rheumatoid arthritis and the
      mechanism of its regulation].

PMID- 15469105
TI  - [Morphological and electrophysiological study of dorsal commissural nucleus].

PMID- 15469106
TI  - [Progress in the study of estrogen and estrogen receptors in the hematopoietic
      and immune system].

PMID- 15469107
TI  - [Subunit of voltage-dependent calcium channels in the murine spiral ganglion
      cells].
AB  - OBJECTIVE: To investigate subunit type of voltage-dependent calcium channels in
      the spiral ganglion cells of the mouse. METHODS: The spiral ganglion cells were
      dissected from cochleae of neonatal mice and cultured for 24 h. Total RNA was
      extracted from cultured spiral ganglion cells. After reverse transcription,
      resulting cDNA was amplified by polymerase chain reaction (PCR) with primers
      targeted to nucleotide sequences corresponding to 7 different calcium channel
      subunits. The types of calcium channel subunits were identified by PCR analysis
      and nucleotide sequencing. RESULTS: Reverse transcription (RT)-PCR products
      representing subunit gene expression were strongly and consistently amplified for
      alpha1 D, alpha1 E, alpha2/delta, beta1 and beta3. Nucleotide sequencing
      confirmed the identity of mouse cochlear subunit cDNAs. CONCLUSIONS: alpha1D,
      alpha1E, alpha2/delta, beta1 and beta3 subunits are expressed in spiral ganglion
      cells. And the coexpression of alpha1D and alpha1 E demonstrate the presence of L
      type and R-type calcium channels in mammalian spiral ganglion cells.

PMID- 15469108
TI  - [Research of the electrophysiological properties of acutely dissociated spiral
      ganglion neurons isolated from mice using patch clamp technique].
AB  - OBJECTIVE: To explore the electrophysiological properties of spiral ganglion
      neurons (SGN) isolated from neonatal mice. METHODS: Ion channel currents of
      acutely trypsin-dissociated spiral ganglion neurons was recorded and analyzed
      using whole-cell variation of the voltage clamp technique. RESULTS: In the
      membrane of SGN, we recorded tetraethylammonium (TEA)-sensitive and 4
      aminopyridine (4-AP)-sensitive outside delayed rectifier potassium currents, A
      type potassium currents and tetrodotoxin-sensitive inside sodium currents. Ion
      channel activity had the character of voltage-dependence. Some cells, which did
      not exhibit sodium currents exhibited, delayed rectifier potassium currents.
      CONCLUSIONS: The electrophysiological properties of acutely dissociated spiral
      ganglion neurons could be reference to the research of the mechanics of auditory
      propagation and the ion channel pharmacology.

PMID- 15469109
TI  - [Endostatin in the treatment of the transplantable model of human laryngeal
      squamous carcinoma in nude mice].
AB  - OBJECTIVE: To evaluate the inhibitory effect of endostatin on tumor growth of
      human laryngeal squamous carcinoma in nude mice and to explore the possible
      mechanism of the inhibition and the possible way of biological therapy. METHODS:
      Nude mice model bearing laryngocarcinoma was established by using human laryngeal
      squamous carcinoma cell line ( Hep-II). The animals were given endostatin (20 mg
      x kg(-1) x d(-1)) or PBS, for 21 consecutive days. The volumes of the
      subcutaneous tumor were observed. The microstructure in which the general 2-step
      immuohistochemical examination was adopted and ultra-microstructural changes of
      carcinoma after administration of endostatin were observed under light and
      electron microscopes for pathology examination. RESULTS: The differences were
      statistically significant for the net mice weight, tumor weight, and tumor volume
      and weight/net mice weight between the treatment group and the control group. The
      restrained percentage of tumor was 45.9%. The necrosis and apoptosis of the tumor
      cell and the angiogenesis reduction were found under light and electron
      microscope in the treatment group. The expression of MVD, PCNA and VEGF of the
      treatment group is lower than that of the control group, and T test showed that P
      < 0.01, P < 0.05, P < 0.05 respectively, the differences were statistically
      significant. CONCLUSIONS: These studies showed that endostatin could
      significantly restrain the development of laryngocarcinoma. The mechanism may be
      due to the effect of antiangiogesis.

PMID- 15469110
TI  - [Largest extension of CO2 laser surgery for laryngeal cancer in experimental
      animals].
AB  - OBJECTIVE: To explore the security and limit resection extension of CO2 laser
      surgery for laryngeal cancer in experimental animal under self-retaining
      laryngoscope. METHODS: Ten experimental dogs were selected and received CO2 laser
      surgery with self-retaining laryngoscope. Vertical partial or supraglottic
      horizontal laryngectomy was performed according to the surgical criteria. All the
      dogs were killed immediately (5/10) or 40 days later(5/10) by using air embolus
      postoperatively. The whole larynx was taken out, and specimens were embedded with
      colloidion and then serially sectioned. Dimension of excision and wound surface
      recovery status were observed. RESULTS: All the operations on experiment animals
      were successful and the results were satisfactory. The excision dimension was the
      same as standard surgery. Gross specimens and serial sectioning staining of 5
      dogs were performed. And the other 5 dogs wound surface had already recovered.
      CONCLUSIONS: CO2 laser surgery was comparable with traditional vertical partial
      laryngectomy and supraglottic horizontal laryngectomy for excision size. Animals
      were able to survive the surgery, wound surface could recover spontaneously. It
      suggested the possibility of extended laryngectomy with laser.

PMID- 15469111
TI  - [Observation of maxillary mucosa restoration after the endoscopic sinus surgery
      operation of chronic sinusitis and nasal polyps].
AB  - OBJECTIVE: To understand the restoration process of the mucosa through the
      continual endoscopic, microscopic, transmission electron microscopic and scanning
      electron microscopic observation of the nasal mucosa after endoscopic sinus
      surgery (ESS). This restoration process of mucosa can be used to appraise the
      effectiveness of the operation. METHODS: Thirty-one cases (53 sides) with chronic
      nasal sinusitis and nasal polyps were selected randomly, which had been undergone
      ESS operation during January to December, 2001. Biopsy of posterior frontanelle
      of the maxillary sinus were performed to observe the mucosa changes before the
      ESS and at 2-3 weeks, 8-11 weeks and 13-16 weeks after the ESS, respectively.
      RESULTS: Epithelia shedding, proliferation, squamous metaplasia, glandular and
      fibrous tissue proliferation and lymphocytes infiltration were observed in all
      cases before the ESS. The microtubule abnormal and mitochondria diminishing and
      expanding existed in all cases. The morphological changes were not significant
      within 2-3 weeks after the ESS compared to the changes before the ESS. Eight
      eleven weeks after the ESS, the nasal cavity turned clean and smooth. The number
      of pillar cells increased and the cilia swelling, short cilia, and many pillar
      cells with microvillus were seen. The number of goblet cells increased.
      Pathological glandular and fibrous proliferation were seen in all cases (53
      sides). The operated cavity was clean and covered completely by epithelia (50
      sides) 13-16 weeks after ESS. The length of cilia increased and arrangement of
      the cilia line was in the same direction. The structure of microtubules was
      clear. The mitochondria was elongated and became dense (49 sides). The
      pathological repairing was at work (3 sides). CONCLUSIONS: After the ESS, the
      recovery of the mucus needs 3 months. Some pathological changes are irreversible
      and the cilia pathological change is related with its restoration. The more cilia
      reserved and timely local cleaned after ESS, the more helpful to the restoration
      of the cilia morphology and function. The effective of ESS can be evaluated
      through the histological-morphological changes. timely local cleaned after ESS,
      the more helpful to the restoration of the cilia morphology and function. The
      effective of ESS can be evaluated through the histological-morphological changes.

PMID- 15469112
TI  - [Use of septo-rhinoplasty in the treatment of traumatic deviated nose].
AB  - OBJECTIVE: To explore the new classification and marking method for traumatic
      deviated nose treated by septo-rhinoplasty. METHODS: Twenty-six selected cases of
      traumatic deviated nose were analysed. There were 5 C-type cases, 12 O-type cases
      and 9 S-type cases. Deviated parameters were measured before and after operation.
      All patients were treated by seven-step method. RESULTS: Clinical data in
      seventeen patients including C-type and O-type were complete. There was
      significant difference in changes of deviated parameters before and after
      operation( t = 6.9031, P = 0.0001). The cure rate was 58.8%, the effective rate
      was 88.2%. CONCLUSIONS: The new clinical classification and marking method for
      traumatic deviated nose are suitable for clinical study. Septo-rhinoplasty is
      effective for traumatic deviated nose.

PMID- 15469113
TI  - [Comprehensive prognostic value of spontaneous and evoked electromyography in
      laryngeal paralysis].
AB  - OBJECTIVE: To determine the comprehensive prognostic value of spontaneous and
      evoked electromyography (EMG) in laryngeal paralysis. METHODS: The
      characteristics of laryngeal EMG of 91 cases with unilateral vocal cord paralysis
      (VCP) after thyroid surgery were assessed. All cases were divided into four
      groups according to the interval of laryngeal EMG after onset, which were group
      one (2 months shorter, n = 13), group two (2 to 4 months, n = 23), group three (4
      to 6 months, n = 36), group four (6 months longer, n = 19). The waveform
      morphology and the amplitude of laryngeal EMG and the highest evoked compound
      muscular active potential (CMAP) of thyroarytenoid muscles were examined and
      analyzed during voluntary tasks. The potential amplitude was showed by the
      percentage of that of the healthy lateral. The criterion of evaluation on evoked
      potential was attained by calculating statistical confidence interval. RESULTS:
      The highest evoked CMAP in group one was significantly lower than that of the
      others (P < 0.05), but no significant difference was observed between group two
      and group three (P > 0.05), so group two and group three were analyzed together.
      There were 2 recovered cases and 11 unrecovered cases in group one. On the basis
      of this criterion that a positive prognosis for laryngeal recovery was indicated
      when the evoked CMAP presented and there was no misdirect generated potential,
      correct prognostic rate was 92% (12/13). There were 11 recovered cases and 48
      unrecovered cases in group two and three. The highest evoked CMAP was much higher
      in the recovered than in the unrecovered, significant difference was observed
      between them (P < 0.001). On the basis of the criterion that a positive prognosis
      for laryngeal recovery was indicated when the highest evoked CMAP was higher than
      26. 4%, correct prognostic rate was 90% (53/59). On the basis of the criterion
      that a positive prognosis for laryngeal recovery was indicated when there was no
      misdirect generated potential and the highest evoked CMAP was higher than 26.4%,
      correct prognostic rate was 93% (55/59). When the interval from onset to
      laryngeal EMG recovering was longer than 6 months, none of these patients had
      return of vocal cord mobility whatever were the outcomes of laryngeal EMG.
      CONCLUSIONS: Correct prognostic rate can be improved if the prognosis of VCP in
      different courses is judged respectively by analyzing comprehensively spontaneous
      and evoked EMG.

PMID- 15469114
TI  - [Non-recurrent laryngeal nerve during thyroid surgery: a report of 4 cases and
      literature review].
AB  - OBJECTIVE: To investigate clinical significance of non-recurrent laryngeal nerve.
      METHODS: Clinical data from 4 cases of non-recurrent laryngeal nerve and related
      literature review was made to acknowledge its incidence, variant types and
      matters concerned during thyroid surgery. RESULTS: Seven hundred and nineteen
      recurrent laryngeal nerves were exposed during 2156 thyroid operations in Xiangya
      Hospital, from which 4 were confirmed to hold non-recurrent laryngeal nerves
      (0.56%). Two cases were found on the right side and the other 2 on the left.
      Among the 4 cases, 3 (patients) were found to have non-recurrent laryngeal nerves
      during reoperation because of voice horse after the first operation. The other
      one was recognized during the first operation. CONCLUSIONS: Non-recurrent
      laryngeal nerve, a rare anomaly, is very vulnerable during thyroid surgery.
      Knowing the related knowledge of the non-recurrent laryngeal nerve and its types
      is helpful to avoid its damage during thyroid surgery.

PMID- 15469115
TI  - [Reconstruction of hypopharyngeal circumferential defects: pharyngogastric
      anastomosis or free jejunal interposition].
AB  - OBJECTIVE: To choose the optimal reconstruction for circumferential defects of
      the hypopharynx between pharyngogastric anastomosis and free jejunal
      interposition is. METHODS: Retrospective review of the archives of 125 patients
      who underwent pharyngoesophageal reconstruction with pharyngogastric
      anastomosis(n = 92) or free jejunal interposition(n = 33). Analysis was confined
      to patient with advanced hypopharyngeal cancer or recurrent laryngeal cancer who
      had hypopharyngeal circumferential defects after tumor ablation. RESULTS: The
      morbidity and mortality associated with reconstructive procedures were
      significantly higher in the pharyngogastric anastomosis group than in the free
      jejunal interposition group (43% versus 21%, P = 0.023 and 11% versus 0%, P = 0.
      048). The risk factors related to complications associated with the procedures
      were reconstruction with pharyngogastric anastomosis (OR 2.97; 95% CI 1.14; 7.76)
      and albumin < 40.0 g/L(OR 2.87; 95% CI 1.33; 6.16) . The occurrence of swallow
      obstruction or regurgitation was higher in the pharyngogastric anastomosis group
      than in the free jejunal interposition group(76% versus 12%, P = 0.00). Patients
      in the pharyngogastric anastomosis group had lost weight of 3.3 kg (95% CI - 5.7;
      - 1.0) postoperatively, on the contrary, patients in the free jejunal
      interposition group had gained weight of 2.8 kg(95% CI 0.9; 4.7) postoperatively.
      CONCLUSION: Patients reconstructed with free jejunal interposition had lower
      mortality and complications than with pharyngogastric anastomosis. Furthermore,
      the former seems to have better quality of life than the latter. The first choice
      of reconstructive strategy for hypopharyngeal circumferential defects is free
      jejunal interposition.

PMID- 15469116
TI  - [Application of 99mTc(V)-dimercaptosuccinic acid imaging in detecting neck
      metastases in patients with oral squamous cell carcinoma].
AB  - OBJECTIVE: To evaluate the applicability of 99mTc(V) -dimercaptosuccinic acid
      (99mTc (V) -DMSA) imaging in detecting neck metastases in patients with oral
      squamous cell carcinoma. METHODS: Single photon emission computer tomography
      (SPECT) scintigraphy with 99mTc(V) -DMSA was performed on 32 patients with
      primary squamous cell carcinoma in oral cavity. The coronal aspect of SPECT image
      was chosen, the region of interest (ROI) of the affected neck was drawn, and the
      radioactivity uptake value of the ROI was given by the computer to compare with
      the contralateral neck. The results of 99mTc(V) -DMSA were compared with
      postoperative pathological studies. For false positive lymph nodes, semi
      continuous slice was carried out for pathology examination. RESULTS: The
      sensitivity, specificity and accuracy of 99mTc(V) -DMSA imaging for detecting
      metastatic lymph nodes were 75.0%, 90.0% and 84.4% respectively. The ROI values
      of the affected neck are higher than that of the contralateral part in the 9
      positive patients (t = 8.128, P = 0.000 04). Metastasis was not found in the
      enlarged lymph nodes of the false positive patients. CONCLUSIONS: 99mTc(V) -DMSA
      SPECT imaging has fairly high affinity with metastatic lymph nodes in the neck
      especially in the cN0 patients and is helpful for designing proper neck
      dissection.

PMID- 15469117
TI  - [Comparison of prevalence rates of secretory otitis media in Hong Kong Chinese
      children with western populations].
AB  - OBJECTIVE: To investigate the prevalence rate of secretory otitis media (SOM) in
      Hong Kong Chinese children and further compare the results with the western
      studies. METHODS: From 1995 to 1998, primary schools, kindergartens and nurseries
      were selected by stratified randomization in Hong Kong of China. Six thousand
      eight hundred and seventy-two children of age 2 to 7 were examined on-site in the
      school premises by the otolaryngologist and audiologist with otoscope and
      tympanometry respectively. In order to achieve standardization comparisons, our
      raw data were retrieved and the prevalence rates were recalculated according to
      the various diagnostic criteria set by the western studies. RESULTS: The
      prevalence of SOM in the age-groups 2-3, 4-5 and 6-7 of the present study ranged
      from 5.2% to 21.6% if criteria were set to clinical otoscopic findings and ranged
      from 7.3% to 30.7% if criteria were based on tympanometric findings. The
      variations in the diagnostic criteria with tympanometric findings also lead to a
      deviation of prevalence rates with the same set of data. Regardless of the
      criteria set for investigations, there are no significant differences between our
      findings and those of the western studies with the same age groups. Prevalence
      rates decrease as age increases. CONCLUSIONS: The prevalence rates of SOM in
      Chinese children of age 2-3, 4-5 and 6-7 in Hong Kong are not significantly
      different from those reported in the literature of the West.

PMID- 15469118
TI  - [Measurement of respiratory ciliary beat frequency quantified with high-speed
      digital microscopy].
AB  - OBJECTIVE: To accurately quantify the respiratory cilia activity, a high-speed
      phase-contrast imaging and ciliary beat frequency (CBF) analysis method were
      introduced. METHODS: Airway ciliated cells, from rabbit trachea, mouse trachea
      and human nose, were prepared by primary culture of airway epithelial cells.
      Phase-contrast images were detected with a digital high-speed camera, a
      progressive scan charge-coupled device(CCD) that provided images (648 pixels x
      200 lines) at 240 frames per second (fps). A data analysis approach, which can
      measure the period [frequency (Hz) = 1/period] of each ciliary beat cycle to
      match the high temporal resolution of the image acquisition rate, was also
      introduced. RESULTS: The high signal-to-noise ratio of gray waveform was obtained
      by interactively selecting the optimal region of interest. The frequency of each
      ciliary beat cycle was determined from the period of each cycle of the gray 
      intensity waveform. At 30 degrees C, the basal CBF (x +/- s(x-)), from mouse,
      rabbit and human, were (15.6 +/- 0.7) Hz (n = 5), (13.2 +/- 0.9) Hz (n = 7), and
      (13.4 +/- 1.1) Hz (n = 5), respectively. No statistical difference was found
      among groups (P > 0.05). In response to extracellular ATP, CBF had a rapid
      increment that could occur in seconds, a behavior suggesting the necessity of the
      high temporary resolution data acquisition system. CONCLUSIONS: This ease of
      recording and replaying high-speed images may be useful in analyzing different
      phases and forms of ciliary beat patterns and perhaps in the diagnosis of cilia
      dysfunction-related diseases.

PMID- 15469119
TI  - The American healthcare industry is in the midst of a construction boom.

PMID- 15469120
TI  - The business case for better buildings.
AB  - The buildings in which customers receive services are inherently part of the
      service experience. Given the high stress of illness, healthcare facility designs
      are especially likely to have a meaningful impact on customers. In the past, a
      handful of visionary "healing environments" such as the Lucille Packard
      Children's Hospital at Stanford University in Palo Alto, California; Griffin
      Hospital in Derby, Connecticut; Woodwinds Health Campus in St. Paul, Minnesota;
      and San Diego Children's Hospital were built by values-driven chief executive
      officers and boards and aided by philanthropy when costs per square foot exceeded
      typical construction costs. Designers theorized that such facilities might have a
      positive impact on patients' health outcomes and satisfaction. But limited
      evidence existed to show that such exemplary health facilities were superior to
      conventional designs in actually improving patient outcomes and experiences and
      the organization's bottom line. More evidence was needed to assess the impact of
      innovative health facility designs. Beginning in 2ooo, a research collaborative
      of progressive healthcare organizations voluntarily came together with The Center
      for Health Design to evaluate their new buildings. Various "Pebble Projects" are
      now engaged in three-year programs of evaluation, using comparative research
      instruments and outcome measures. Pebble Projects include hospital replacements,
      critical care units, cancer units, nursing stations, and ambulatory care centers.
      The Pebble experiences are synthesized here in a composite 3oo-bed "Fable
      Hospital" to present evidence in support of the business case for better
      buildings as a key component of better, safer, and less wasteful healthcare. The
      evidence indicates that the one-time incremental costs of designing and building
      optimal facilities can be quickly repaid through operational savings and
      increased revenue and result in substantial, measurable, and sustainable
      financial benefits.

PMID- 15469121
TI  - A challenging road toward a rewarding destination.

PMID- 15469122
TI  - What really drives better outcomes?

PMID- 15469123
TI  - Facility design focused on patient safety.

PMID- 15469124
TI  - Using focus groups to understand physicians' and nurses' perspectives on error
      reporting in hospitals.
AB  - BACKGROUND: To increase error reporting, a better understanding of physicians'
      and nurses' perspectives regarding medical error reporting in hospitals, barriers
      to reporting, and possible ways to increase reporting is necessary. METHODS: Nine
      focus groups--four with 49 staff nurses, two with 10 nurse managers, and three
      with 30 physicians--from 20 academic and community hospitals were conducted in
      May-June 2002 in the St. Louis metropolitan area. Qualitative analysis of focus
      group transcripts characterized participants' perspectives. RESULTS: Although
      participants knew they should report errors associated with serious adverse
      events, there was much uncertainty about reporting less serious errors or near
      misses. Nurses were more knowledgeable than physicians about how to report
      errors. All groups mentioned barriers to reporting, such as fear of reprisals and
      lack of confidentiality, time, and feedback after an error is reported. Some
      physicians doubted the benefit of reporting errors, but, generally, both
      physicians and nurses agreed that reporting was intended to change practice and
      policy to promote patient safety. CONCLUSIONS: A culture characterized by
      anonymous reporting, freedom from repercussions, and feedback about error reports
      should promote error reporting.

PMID- 15469125
TI  - A modified outpatient prescription form to reduce prescription errors.
AB  - BACKGROUND: Given current knowledge of prescribing errors, standard paper
      prescription forms are inadequate for promoting high-quality outpatient
      prescriptions. A modified prescription form was designed and evaluated to reduce
      outpatient prescription errors. METHODS: Eleven providers (nine physicians, two
      nurse practitioners) in an adult internal medicine clinic participated in a
      before-after trial of a modified paper prescription form. The modified form
      contained prompts for medication name, form, strength, dose, route, frequency,
      refills, quantity, indication, and additional directions. Writing the indication
      has face validity and has been recommended in the literature and has been useful
      in the practice. Providers used the modified prescription forms for one month.
      Prescriptions were reviewed using the records of the outpatient pharmacy located
      within the same building as the clinic. RESULTS: A total of 443 prescriptions
      were reviewed during the study period; 150 (34%) were completed using modified
      forms. Pharmacists documented problems with 2.3% of prescriptions (9/293 standard
      and 1/150 modified). Modified prescription forms significantly reduced clinically
      important prescribing problems compared to standard forms (p = .007). Based on
      the legal requirements of a prescription, modified forms decreased omission
      errors compared to standard forms (p = .01). DISCUSSION: Modified prescription
      forms reduced clinically important prescribing problems and prescription omission
      errors compared to standard forms.

PMID- 15469126
TI  - A cognitive aid for cardiac arrest: you can't use it if you don't know about it.
AB  - BACKGROUND: A cognitive aid developed by the Department of Veterans Affairs (VA)
      and distributed to all VA facilities provides caregivers with information to
      minimize omission of critical steps when diagnosing and treating cardiac arrest.
      In 2002, caregivers were surveyed about the usefulness of the cognitive aid and
      the success of its dissemination throughout the VA. METHODS: Fifty randomly
      selected VA hospitals were sent a letter to alert them of the upcoming survey.
      Twenty surveys were sent to each of the selected hospitals with instructions to
      distribute the survey to specific caregiver types. RESULTS: Nine (18%) of the VA
      hospitals had not used the cognitive aid tool because of dissemination problems.
      Of the 565 caregivers responding to the survey, 59% (332) were aware of the
      cognitive aid. Of these 332, 96% agreed that putting the cognitive aid on code
      carts is a good idea. There were 234 respondents who were both aware of the
      cognitive aid and had been involved in at least one code within the past 30 days.
      Of these 234, some 29 (12%) used the aid during a code, 28 of whom agreed that
      the cognitive aid was helpful during the code. DISCUSSION: Both new and
      experienced caregivers find the cognitive aid helpful when responding to "code"
      situations. However, cognitive aids cannot be helpful if theintended users are
      unaware of their availability. Dissemination and awareness of the aids can be
      problematic in large health care systems.

PMID- 15469127
TI  - Readmissions for venous thromboembolism: expanding the definition of patient
      safety indicators.
AB  - BACKGROUND: The Agency for Healthcare Research and Quality (AHRQ) defines its
      venous thromboembolism (VTE) patient safety indicator (PSI) as surgical cases
      with a secondary diagnosis of pulmonary embolism or deep vein thrombosis. Short
      term readmissions for VTE are excluded because most state administrative
      databases are unable to track readmissions. METHODS: Patients meeting the AHRQ
      VTE PSI definition and those readmitted with a VTE principal diagnosis within 30
      days of a prior surgical hospitalization were identified on the basis of
      inpatient discharge data. RESULTS: A total of 4,906 surgical discharges in New
      York met the AHRQ VTE PSI definition in 2001. An additional 1,059 cases of VTE
      were found when surgical patients with a short-term readmission for VTE were
      identified. Patients readmitted with VTE were less likely to die but were more
      likely to have a pulmonary embolism and were more likely to be white and non
      Hispanic compared to those who met the AHRQ VTE PSI definition. DISCUSSION: Short
      term readmissions for VTE represent potentially important cases to capture when
      monitoring adverse events. Prophylaxis, monitoring, and patient education may be
      required after hospital discharge to prevent or treat VTE as early as possible.
      Data systems that can track patients across multiple admissions to identify
      complications resulting in short-term readmissions are needed.

PMID- 15469128
TI  - What are the facilitators and barriers in physician organizations' use of care
      management processes?
AB  - BACKGROUND: Care management processes (CMPs) such as disease registries, reminder
      systems, performance feedback, case management, and self-management education can
      improve chronic illness care, yet 50% of physician organizations have instituted
      few if any CMPs. METHODS: Site-visit interviews were conducted with 158 leaders
      at 15 physician organizations, with 3 organizations (1 large medical group, 1
      small medical group, and 1 independent practice association [IPA]) chosen
      randomly in most cases in each of five communities. RESULTS: Seven of the 15
      organizations had implemented CMPs minimally or not at all. CMPs were most common
      for diabetes and least common for depression; no IPAs had achieved significant
      CMP implementation for any of the conditions. The two most commonly mentioned
      facilitators were strong leadership and organizational culture valuing quality.
      The top five barriers were poor financial situation, reimbursement that does not
      reward high quality, inadequate information technology, physician resistance, and
      physicians being too busy. DISCUSSION: Strong leadership and a quality-valuing
      culture are important facilitators of improved chronic care, but if insurers do
      not reward chronic care improvement, it is unlikely that CMPs will become
      permanently institutionalized in physician organizations.

PMID- 15469129
TI  - Using "no problem found" in infusion pump programing as a springboard for
      learnning about human factors engineering.
AB  - BACKGROUND: A hospital took a second look at a device error with a syringe pump
      in which a dose of fentanyl was delivered in half the anticipated time. When the
      nursing staff could not reproduce the error, the pump was sent to biomedical
      engineering where "no problem was found." The biomedical staff subsequently
      performed another analysis, which led to discovery of the possible cause of the
      problem. MOBILIZING FOR HFE: A human factors engineering (HFE) task force, in
      considering the fentanyl delivery issue, identified a need to educate nursing and
      engineering on such incidents and to consider the consequences of override
      features. The HFE task force then reviewed a tool kit for briefing clinical units
      on education of staff on clinical safety issues. HFE ANALYSIS: Efforts to
      maximize device customization or simplification can have negative HFE
      consequences. The decision to allow for function overrides or nontraditional
      equipment use must be weighed against the potential compromises in patient
      safety. SUMMARY: The problems that arise from the interface between humans and
      devices are not limited to intravenous pumps or even medical devices. Awareness
      of the potential for HFE design flaws can be critical in reducing harm in health
      care.

PMID- 15469130
TI  - To telemedically err is human.
AB  - BACKGROUND: As telemedicine alters the process of health care and introduces new
      technology, the extent to which it introduces new errors or allows for the
      occurrence of familiar errors needs to be examined. TELEMEDICINE'S IMPACT ON
      PATIENT SAFETY FEATURES OF TRADITIONAL CARE: The accuracy of diagnostic decisions
      reached via telemedicine can be directly affected by the technology's limitations
      and the care providers' lack of training. Telemedicine could increase the risk of
      familiar types of patient-provider communication failure and introduce the
      possibility of cumulative errors. TELEMEDICINE'S IMPACT ON NEW CARE FEATURES AND
      CONCEPTS: Telemedical applications that use the Internet to enhance disease
      management and detection and monitoring of symptoms may place the privacy and
      confidentiality of individual health information at risk, which imposes a
      possible barrier to communication. In addition, home care patients' functional
      limitations need to be addressed by human factors engineering. RECOMMENDATIONS:
      Patient safety should be integrated in organizational readiness and budget
      planning for telemedical interventions in hospitals, academic settings, nursing
      homes, home care agencies, and other health care settings. Specific
      recommendations are proposed for the development and diffusion of standards in
      telemedical care, risk management and reduction, and continuous quality
      improvement. SUMMARY AND CONCLUSIONS: To address patient safety and provide high
      quality care, a framework for addressing and examining telemedical errors needs
      to be established.

PMID- 15469131
TI  - Caring for the families that feed the world.

PMID- 15469132
TI  - "La verdad" and risk communication--strategies for communicating results of
      environmental exposure tests to individuals.

PMID- 15469133
TI  - Laboratory workers and musculoskeletal disorders--examining ergonomic risk
      factors and solutions.

PMID- 15469134
TI  - Identifying requirements for an occupational health and safety information
      system.

PMID- 15469136
TI  - Seasonal and migrant agricultural workers: a neglected work force.
AB  - A desperate need exists to provide occupational health services to migrant and
      seasonal farm workers in the United States. There are unique challenges related
      to this endeavor, and the authors have attempted to explain some of the issues
      that have not been previously discussed in a forthright manner. In doing so, it
      is likely that some controversy related to the topic has been introduced.

PMID- 15469135
TI  - Sleep deprivation and injuries in part-time Kentucky farmers: impact of self
      reported sleep habits and sleep problems on injury risk.
AB  - Part-time farmers who hold off-farm jobs may be at risk for injuries because of
      impaired performance resulting from inadequate sleep. For this study, 1004 part
      time male Kentucky farmers completed a telephone interview for the 1994 to 1995
      National Institute for Occupational Safety and Health-funded Farm Family Health
      and Hazard Surveillance Project. Questions were included about demographics,
      sleep habits, and injury occurrence. Twelve percent of the farmers reported an
      injury requiring medical intervention in the previous year. Farmers reported
      sleeping an average of 7.6 hours daily. Approximately 6.7% of the sample had
      three symptoms of sleep apnea. Although hours of sleep were not related to injury
      incidence, sleep medication use (odds ratio [OR] = 2.11, 95% confidence interval
      [CI] = 1.01 to 4.40) and presence of three sleep apnea symptoms (OR = 2.48, 95%
      CI = 1.13 to 5.41) were related to injury incidence. These data support the need
      for further research to examine sleep habits and promote strategies that reduce
      the risk for injuries caused by lack of sleep.

PMID- 15469137
TI  - Agricultural health: a new field of occupational health nursing.
AB  - 1.) Agriculture remains one of the most dangerous industries in America. To serve
      this worker population, agricultural health is emerging as a new nursing
      specialty in which nurses can use their vision to establish new areas of
      practice. 2.) Nurses who are a member of the farming audience can be effective
      agents of change because they know the audience in a personal way. 3.) To
      establish a new agricultural nursing specialty, one must overcome obstacles
      including uncertain funding, a rapidly changing work environment, worker
      preference for independent decision making, and no existing standards to guide
      the process. 4.) Using the early adopters of new ideas in a community can improve
      the acceptance from community leaders.

PMID- 15469138
TI  - Strengthening the nursing curriculum: an interdisciplinary course addressing
      agricultural health and safety.
AB  - 1.) Agricultural work is a dangerous occupation and incorporating content on
      agricultural health and safety issues into the nursing curriculum presents a
      challenge. 2.) The traditional strategy for dealing with these issues has been a
      single discipline approach. 3.) An interdisciplinary course bringing together
      faculty and students from the disciplines of agriculture, nursing, and public
      health proved successful in addressing this content in the curricula of the
      disciplines involved. 4.) When teaching agricultural health and safety content,
      it is essential to emphasize an interdisciplinary approach and frame the course
      in the context of rurality.

PMID- 15469139
TI  - The risky business of production agriculture: health and safety for farm workers.
AB  - The lifestyles of employees affect their work and their health. Occupational
      health nurses need to know as much as possible about employees to render the best
      care possible. Production agriculture is a risky business performed by many
      employees. By understanding the risks involved, occupational health nurses can
      optimize the health of workers in the off farm and on farm contexts of their
      lives. Managers and supervisors need to realize that investment in farm health
      and safety can yield financial benefits in terms of decreasing lost workdays
      caused by injury and illness and increased morale through public recognition of
      the importance of agricultural production.

PMID- 15469140
TI  - The impact of contingent workers on the workplace.

PMID- 15469141
TI  - Professional responsibility of surgeons versus political responsibility!

PMID- 15469142
TI  - [Conducting a surgical intervention without permission...].

PMID- 15469143
TI  - Legal aspects of on-line pharmacy.

PMID- 15469144
TI  - Legal aspects of on-line pharmacy: free movement of goods is not tantamount to
      free provision of services!

PMID- 15469145
TI  - Accreditation in Belgium: a 10 years' experience.

PMID- 15469146
TI  - Rationale for hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment
      or prevention of peritoneal carcinomatosis.
AB  - Up to now, the prognosis of peritoneal carcinomatosis from GI tract cancers
      remains very poor. Intraperitoneal hyperthermic chemotherapy has been proposed in
      the prevention or treatment of peritoneal carcinomatosis. The rationale for this
      locoregional approach comes from a better knowledge of the physiopathology of the
      disease. Intraperitoneal chemotherapy achieves high local drug concentration with
      limited systemic toxicity. It should be performed during or immediately after
      surgery to be effective towards microscopic residual tumor cells. A synergistic
      cytotoxic effect has been demonstrated when heat is combined with antineoplastic
      drugs. Intraperitoneal hyperthermic chemotherapy might not be regarded as the
      panacee but as a promising step in the management of peritoneal carcinomatosis.
      Some randomized studies of gastric cancer with macroscopic serosal invasion have
      suggested the efficacy of hyperthermic intraperitoneal chemotherapy for the
      prevention of peritoneal carcinomatosis. In patients with peritoneal
      carcinomatosis, some studies suggest, in selected cases, the positive effect of
      hyperthermic intraperitoneal chemotherapy on survival, when combined with
      cytoreductive surgery.

PMID- 15469147
TI  - Carotid endarterectomy in octogenarians and nonagenarians : is it worth the
      effort?
AB  - PURPOSE: The safety, effectiveness and cost issues of carotid endarterectomy
      (CEA) in the elderly patient have been debated due to the limited life expectancy
      and presumably increased rate of complications. This is despite multiple reports
      in the literature of excellent results in this population. To further examine
      this issue, we compared characteristics of three populations who underwent CEA at
      our institution: 53-79 year old patients (youngest group), 80-89 years old
      patients (middle group), and 90-98 year old patients (oldest group). METHODS:
      Medical and financial data were obtained by retrospective review of hospital
      charts and billing records. We analyzed 266 random CEAs performed in 251 patients
      in the youngest group, 280 CEAs performed in 247 patients in the middle group and
      19 CEA in 16 patients in the oldest group performed between 2/1/90 and 2/5/01.
      RESULTS: Comparing each CEA group, there were no differences in gender (males:
      56% vs. 51% vs. 53%), incidence of preoperative symptoms (43% vs. 43% vs. 42%),
      hypertension (68% vs. 60% vs. 42%), combined perioperative death and stroke rate
      (1.8% vs. 2.1% vs. 10%) or other complications (11% vs. 10% vs. 10%). Significant
      differences (p<0.05) were noted between the groups in incidence of diabetes (33%
      vs. 51% vs. 5% in each group), and heart disease (28% vs. 38% vs. 21%). Length of
      stay for admissions for CEA only were also similar in all three groups (2.37 days
      vs. 2.67 days vs. 2.36 days). A cost analysis of the earliest 230 patients in the
      entire series examining hospital cost per case revealed similar data for the < 80
      years old and > 80 year old patients ($7,842 vs. $9,400). CONCLUSIONS: Carotid
      endarterectomy can be performed in the elderly as safely and cost effectively as
      in the younger population.

PMID- 15469148
TI  - Amputations of the lower limb--an overview on technical aspects.

PMID- 15469149
TI  - Early fitting of artificial limbs to amputated lower limbs.
AB  - Specific rehabilitation of patients with amputated lower limbs is first of all
      rehabilitation to walk with a prosthesis (artificial limb). After 20 years of
      practice of prosthetic early fitting for lower limbs amputees using practice
      prosthesis, the authors suggest that this technique is still up-to-date. The
      taking charge of amputated patients by a specialised team is an important element
      if one wants to achieve a good functional result. A rehabilitation milieu, where
      the new amputee is with a large number of patients with the same pathology, also
      constitutes a framework that is reassuring as well as stimulating and allows the
      patient to imagine the situation in which he/she can find himself/ herself a few
      weeks later.

PMID- 15469150
TI  - From unstable internal fixation to biological osteosynthesis. A historical
      overview of operative fracture treatment.
AB  - The first techniques of operative fracture treatment were developed in the 19th
      century. In fact, these methods only consisted of an open reduction of the
      fracture followed by a usually very unstable fixation. This method gave rise to
      the combination of the disadvantages of the conservative and the operative
      fracture treatment: the fracture had to be opened with a real risk for (sometimes
      lethal) infection, the bone healing was disturbed, there was muscular atrophy and
      joint stiffness. The successes were very rare and catastrophes were often seen.
      Kuntscher's endomedullary rods can be considered as the first useful implants in
      the treatment of diaphyseal fractures. Reaming of the medullary canal and the
      development of interlocking nails have enlarged the indications for
      intramedullary nailing. The classic Dynamic Compression Plates from the seventies
      were the key to a very rigid fixation, leading to primary bone healing.
      Nevertheless, the use of strong plates and reamed nails disturbed the
      vascularisation of the bone fragments, leading to a high infection rate
      (particularly in open fractures) and delayed union (particularly after plate and
      screw fixation). These insights lead to the development of the "biological
      osteosynthesis" : a terminology introduced to indicate a new type of
      osteosynthesis leading to a sufficiently stable fixation of the bone fragments
      allowing early mobilisation, but without major disturbance of the
      vascularisation. The unreamed nail can also be considered as a biological
      osteosynthesis and in a lot of cases it is the implant of choice for tibial and
      femoral shaft fractures, especially in polytrauma patients. Finally, some new
      devices contributing to the principles of biological osteosynthesis like locking
      plates and the LIS-System are gaining popularity.

PMID- 15469151
TI  - Fractures of the distal radius: a contemporary approach.
AB  - The fracture of the distal radius is the most common fracture we treat. Although
      sometimes stated otherwise, the outcome of these fractures is not uniformly good
      regardless the treatment instituted. A thorough understanding of the anatomy and
      biomechanics of the wrist is a prerequisite when treating these lesions. The
      literature proves that there is a strict relationship between the quality of
      anatomical reconstruction and the long-term functional outcome. We try to clarify
      the complex functional anatomy of this region. No single treatment is the
      solution for every type of fracture in every kind of patient. Based on the
      functional anatomy, we analyze the actual treatment possibilities and try to
      develop strategies in the choice of treatment for different fracture types in
      different patient groups. Treatment aims should be to reconstruct the anatomy as
      good as possible, to guarantee that there is no loss of reduction and to allow
      for a functional after treatment as soon as possible.

PMID- 15469152
TI  - Medium to long-term results with the cementless threaded Acetabular Munich II
      type cup.
AB  - Compared to pressfit cups, little information exists about the results of screwed
      cups in hip arthroplasty. 51 cementless or hybrid (cemented stem) primary total
      hip replacements with a cementless corundium blasted titaniumn alloy threaded
      Aesculap Munich II type cup were examined with a mean follow up of 7.9 years. 23
      of the patients were male and 28 patients were female. From these cups 22 were
      implanted on the right side and 29 on the left. The results were compared to 53
      patients (28 male, 25 female, 29 right side, 24 left side) with the threaded
      Aesculap Munich I type cup, that has a smooth surface and a direct contact of
      bone with the polyethylene inlay. The mean follow up ws 10.2 years. The early and
      medium to long-term clinical and radiographic results show an encouraging
      improvement of the Merle d'Aubigne Score of the type II cup compared to the type
      I cup. Two of the Aesculap type Munich II cups had to be revised; four showed
      radiologic signs of loosening. In conclusion, the threaded Aesculap cup type
      Munich II seems to be a decisive advance in the development of threaded
      acetabular hip cups. The intermediate results exceed those from smooth-surface
      screwed rings and compare favourably with those from cemented cups and with those
      from cementless press-fit metal-backed cups.

PMID- 15469153
TI  - Comparison of Shouldice and Lichtenstein repair for treatment of primary inguinal
      hernia.
AB  - PURPOSE: The purpose of this study was to compare the outcome following
      Lichtenstein open mesh repair or Shouldice repair for the surgical treatment of
      primary unilateral inguinal hernias. PATIENTS AND METHODS: Patients with primary
      unilateral inguinal hernia who underwent a Shouldice repair (n: 120) and a
      Lichtenstein open mesh techniques (n: 121) between 1994 and 1998 were evaluated
      retrospectively. Operation time, hospital stay, postoperative analgesic
      consumption and complications, return to work and recurrence after surgery were
      assessed and compared. RESULTS: The two groups were comparable regarding age,
      types of hernia and the follow-up interval. There were no significant differences
      in hospital stay and postoperative complications. The number of recurrences
      differed significantly between the groups with five in the Shouldice group (4.1%)
      and one in the Lichtenstein group (0.8%) (p < 0.05). The need of analgesic
      medication after mesh repair was significantly lower than the Shouldice group
      (3.9+/-1.4 vs. 4.9+/-1.6 gr. p < 0.05). The operation time was 36+/-14 min. for
      Lichtenstein repair and 61+/-12 min. for Shouldice repair (p < 0.05). The time
      for return to work was shorter in Lichtenstein group (17+/-4 days) compared to
      Shouldice group (25+/-5 days) (p < 0.05). CONCLUSION: Shorter operation time,
      faster return to work, less need to analgesia and lower recurrence rate, shows
      the superiority of Lichtenstein repair against Shouldice repair in the surgical
      repair of primary unilateral inguinal hernia.

PMID- 15469154
TI  - Inguinal hernia repair in general surgical practice in 2004: more than
      laparoscopy, training is the keyword.

PMID- 15469155
TI  - Late complications of incisional hernias following prosthetic mesh repair.
AB  - BACKGROUND: Incisional hernias still continue to be a serious problem for
      surgeons. In this study, we aimed to investigate the effects of polypropylene
      mesh and mersilene mesh, which are frequently employed in incisional hernias, as
      well as the effects of their application techniques on late complications.
      METHODS: Two-hundred-sixty-four open abdominal hernia repairs were performed
      between 1986--2000, using prosthetic materials: polypropylene mesh and mersilene
      mesh were used in hernia repair. Mesh was placed as onlay, underlay and sandwich
      techniques. Follow-up data were obtained from medical records. RESULTS:
      Comparisons were made with respect to surgical techniques and to late
      complications such as recurrence, enterocutaneous fistula, intestinal
      obstruction, and infections. Enterocutaneous fistulas developed in two patients.
      Recurrence occurred in 6.4 per cent. Chronic infection and wound sinus formation
      occurred in 5 per cent. The causes of recurrence included smoking, cellulitis,
      chronic infection/sinus tract, upper abdominal localization, and obstruction.
      Fistula formation occurred in patients with no peritoneal prevention, which was
      statistically significant (p=0.012). Chronic infection/sinus tract was high in
      patients for whom mersilene mesh was used, and enterocutaneous fistula occurred
      in 2 patients. CONCLUSION: To prevent late complications, it is necessary to
      avoid the contact of mesh with bowel.

PMID- 15469156
TI  - Predicting factors for mortality in the penetrating abdominal trauma.
AB  - PURPOSE: penetrating abdominal trauma (PAT) is still a serious problem all over
      the world. This study was made to define and discuss the factors that could
      affect mortality in the PAT. METHODS: the records of 1048 patients hospitalized
      and operated for PAT at Dicle University Hospital (DUH) between January 1990 and
      December 2001 were retrospectively reviewed. Patients (n = 1048) were divided
      into two groups: "Healthy Group" (HG) (n = 942) and "Deathly Group" (DG) (n =
      106). The epidemiological and clinical features were evaluated as probable risk
      factors for mortality. The risk factors for mortality were revealed using
      univariate and multivariate analyses. RESULTS: a total of 1048 patients [937
      (89.4%) male, 111(10.6%) female] with PAT were included in this study. The
      mortality rate (22.5%) of female patients was significantly higher than (8.6%)
      that of male patients (p = 0.000). The mean age was 30.01+/-63.9 (14-74) years
      and 30+/-12.5(15-71) years in the HG and DG consecutively (p = 0.85). The average
      interval between injury and operation (IBIO) was 2.09+/-1.3 (0.5-3) and 6.9+/
      11.4 (1-6.1) hours in the HG and DG respectively (p = 0.000). Presence of shock
      on admission (PSDA) was determined in 87 patients and in 96 patients in the HG
      and DG respectively (p = 0.000). The mortality rate (14.9%) in patients
      presenting gunshot wounds (GSW) was significantly higher than (2.7%) that of
      patients with stab wounds (SW) (p = 0.000). The average number of injured
      intraabdominal organs (NIAOI) was 1.98+/-1.08 (1-7) and 4.67+/-1.99 (1-13) in the
      HG and DG respectively (p = 0.000). Mortality rates were 72.7% in cardiac injury,
      30% in great vessels injuries, 32.6% in cranial injury, and 21.5% in major
      extremity and pelvic injury (p = 0.000). The average penetrating abdominal trauma
      index (PATI) was 11.78+/-9.44 (1-58) and 46.24+/-22.18 (15-119) in the HG and DG
      respectively (p = 0.000). In multivariate analyses, female gender [Odds Ratio
      (OR) = 10.74, 95% Confidence Interval (CI) = 3.03-38.12, P = 0.000], the long
      IBIO (OR = 1.82, CI = 1.39-2.40, P = 0.000), PSDA (OR = 94.45, CI = 28.32-314.95,
      P = 0.000), presence of cranial injury (OR = 0.03, CI = 0.002-0.363, P = 0.006)
      and high PATI (OR = 1.14, CI = 1.09-1.19, P = 0.000), were found significantly
      important for mortality. CONCLUSION: we determined that conditions such as,
      female gender, long interval between injury and operation, presence of shock on
      admission, presence of cranial injury and high PATI were predicting factors for
      mortality in PAT.

PMID- 15469157
TI  - Jugular foramen schwannoma: surgical experience in six cases.
AB  - PURPOSE: Schwannomas of the lower cranial nerves are rare tumours. We have
      surgical experience in six patients. MATERIAL AND METHODS: We have
      retrospectively reviewed the files of the six patients with jugular foramen
      schwannomas that were treated in multidisciplinary collaboration in the
      departments of neurosurgery and ENT. RESULTS: From a clinical point of view, the
      most important finding was that these tumours usually mimic a vestibular
      schwannoma. The imaging findings however always allowed the differentiation. The
      surgical technique included in all cases a suboccipital approach for the
      intracranial part. When large, the extracranial extension had to be removed
      through a lateral cervical or transfacial approach. There was no mortality and
      minor morbidity, with good functional outcome. In subtotally removed tumours,
      recurrence occurred. CONCLUSION: A combined neurosurgical and ENT approach allows
      for safe removal of these often large skull base tumours.

PMID- 15469158
TI  - Operative outcome of minimal access aortic valve replacement versus standard
      procedure.
AB  - BACKGROUND: to determine the advantages and/or risks of minimal access aortic
      valve replacement compared to standard sternotomy procedure. METHODS: from
      January 1997 to December 2001, 271 consecutive adult patients underwent isolated
      aortic valve replacement of which 174 underwent a minimal access procedure (Group
      1) and 97 a standard procedure (Group 2). The preoperative variables of both
      groups were comparable. Retrospective analysis of postoperative outcome was
      performed. RESULTS: follow-up was complete and ranged from 6 months to 4 years.
      Overall in-hospital mortality was 3.3% (respectively 2.8 and 4.1%). No
      statistical difference was noted regarding operative time variables, mortality
      rate and hospital stay. There was a significant higher incidence of revision (p =
      0.018) and late pericardial effusion (p = 0.022) in the minimal access group.
      Also trends were in favour of the standard group for incidence of postoperative
      pneumothorax and pericarditis constrictiva. CONCLUSIONS: minimal access aortic
      valve replacement is a safe and reliable technique, but carries the risk of
      incision-related morbidity. Proper patient selection and perioperative management
      is mandatory.

PMID- 15469159
TI  - Typhoid ileal perforation: surgical experience of 64 cases.
AB  - OBJECTIVE: Intestinal complications of typhoid fever are quite common in
      developing countries. In order to contribute to the improvement of the prognosis
      of typhoid ileal perforation, the authors report their own surgical experience
      PATIENTS AND METHODS: between May 95 and July 98, 64 patients, (31 men and 33
      women), with an average age of 34 years (ranging from 5 to 63 years) underwent
      surgery for typhoid ileal perforation. The surgical techniques used were excision
      suture (n = 31) and resection-ileostomy (n = 33). All the patients were operated
      under similar pre-, per- and postoperative care facilities. RESULTS:
      Postoperative complications were observed in 59 patients (88.1%). The mean
      hospital stay was 30 days (ranging from 8 to 52 days). The overall postoperative
      mortality was 34% (22/64), mainly due to digestive fistula in 11 cases (8 cases
      of anastomotic leak after excision-suture, 3 cases of bowel fistula after
      conservative resection-ileostomy) and to chronic peristomal ulceration in 9
      cases, which led to progressive malnutrition, cachexy and death. CONCLUSION: The
      mortality and morbidity after surgical treatment of typhoid ileal perforation
      remains very high in developing countries. However some recommendations could
      improve the outcome: aggressive resuscitation by intravenous hydratation of 4 to
      6 hours, associated with adequate antibiotherapy, the resection of the last 60
      centimetres of the ileum, in cases of serious abdominal suppuration, and a large
      abdominal washout.

PMID- 15469160
TI  - Biliary pleural fistula as a complication of radiofrequency ablation for liver
      metastasis.
AB  - Radiofrequency ablation (RFA) recently emerged as an efficient and safe local
      ablative method to treat unresecable liver tumours. Currently however, the full
      spectrum of potential complications of RFA remains undetermined. We report a case
      of severe biliary complication, associating main bile duct stricture and biliary
      pleural fistula, arising after extensive RFA for unresectable liver metastasis of
      central location. Treatment consisted of external drainage of the pleural
      effusion and internal endoscopic drainage via a biliary stenting. This
      description of a life-threatening complication emphazises the need to better
      knowledge of the contraindications of RFA, particularly for the treatment of
      large tumours at proximity of main bile ducts.

PMID- 15469161
TI  - Surgical options for complete resectable lung cancer invading the phrenic nerve.
AB  - We describe a 58-year-old male diagnosed with a tumour of the left lung, which on
      subsequent thoracotomy proved to be invading the phrenic nerve. The clinical and
      spirometric outcome of a lobectomy, which resulted in a postoperative ipsilateral
      hemidiaphragmatic paralysis, versus the alternative surgical option of a
      pneumonectomy is discussed.

PMID- 15469162
TI  - Aortic graft infection from appendicitis. A case report.
AB  - Fifteen years after aortobifemoral bypass and five years after left
      femoropopliteal bypass, a 73-year old man presented with a vague abdominal pain
      syndrome. After an extensive work-up, aortobifemoral graft infection was
      suspected; an appendiceal abscess infiltrating the prosthesis was discovered
      during exploratory laparotomy. Appendectomy was performed followed by removal of
      the vascular graft, the latter being replaced by a bilateral axillofemoral
      prosthesis. Aortic graft infection from appendicitis is an extremely rare
      condition; a review of similar cases is presented.

PMID- 15469163
TI  - Cavernous transformation of the portal vein causing jaundice, presenting in the
      form of Wilson's disease.
AB  - The following is a case review of portal vein cavernous malformation presenting
      with intermittent cholestasis and jaundice in a 4 year old child. Correct
      assessment was supported by radiology, later laparoscopy, yet hindered by
      histopathology representative Wilson's disease and elevated urinary copper
      excretion. During surgical procedure the stenosis of the common bile duct
      secondary to extremely dilated portal vein reticulation was solved by Roux-en-Y
      choledochojejunostomy. After a one-year follow up the child remains asymptomatic.

PMID- 15469164
TI  - Idiopathic segmental infarction of right sided greater omentum. Case report and
      review of the literature.
AB  - Idiopathic right segmental infarction of the greater omentum is an uncommon cause
      of acute abdomen. The aetiology is still unclear and the symptoms mimick acute
      appendicitis. We present a case of a 77-year old man with unsignificant medical
      history, admitted with an acute abdomen, in whom the clinical diagnosis was
      unknown until an infarcted segment of right side of the greater omentum was found
      at laparoscopy, and successfully resected. As the aetiology is unknown, we
      highlighted some of the possible theories, and emphasize the importance of
      considering omental infarction in the differential diagnosis of right iliac fossa
      syndrome in cases of acute abdomen.

PMID- 15469165
TI  - Inflammatory pseudo-tumour as an unusual cause of colonic obstruction: a case
      report.
AB  - Inflammatory pseudo-tumour (IPT), also known as inflammatory myofibroblastic
      tumour or plasma cell granuloma, is a benign inflammatory solid tumour that may
      mimic malignancy. The etiology is obscure. Lung, spleen and mesentery are common
      sites of involvement. Colonic occurence is rare. Herein we report a case of IPT
      arising from the hepatic flexura with regard to its radiological, operative and
      histologic findings, that lead to colonic obstruction.

PMID- 15469166
TI  - Primary angiosarcoma of the colon.
AB  - Angiosarcoma of gastrointestinal tract is extremely rare. Since 1948, we can find
      only six reported cases of primary colonic angiosarcoma. The review of the six
      reported cases and a report on the first colonic angiosarcoma to be seen in an
      adolescent male are presented. The treatment of the colon angiosarcoma is wide
      surgical excision. The prognosis is poor. Our case is the second one to be alive,
      more than 18 months after surgery, with no evidence of recurrent disease.

PMID- 15469167
TI  - Necrolytic migratory erythema: first symptom of a glucagonoma. A case report.
AB  - Necrolytic migratory erythema (NME) is a rare skin condition consisting of
      migrating areas of erythema with blisters that heal with hyperpigmentation. NME
      is a pathognomonic feature of a glucagonoma. When confronted with a xerosis cutis
      one should always exclude the possibility of a NME caused by a glucagonoma as
      demonstrated in this case report where the rash was wrongly attributed to an
      acrodermatitis enteropathica due to zinc deficiency. We describe a case of a
      glucagonoma with its classic features, diagnosis and treatment.

PMID- 15469168
TI  - Primary hydatid cyst of vastus lateralis muscle.
AB  - Musculoskeletal system is rarely involved by hydatid cyst,the larval form of
      Echinococcus Granulosus. A 37-year old man was diagnosed as having a cystic mass
      within his left thigh musculature. Preoperative computerized tomography suggested
      an unusual location of echinococcus although serology could not confirm the
      diagnosis. During surgery, a white coloured cyst within left vastus lateralis
      muscle was enucleated. Pathological examination after removal of the mass
      revealed hydatid cyst of vastus lateralis muscle. This case emphasizes that
      hydatidosis should be included in differential diagnosis of any soft tissue mass
      especially in regions where it is endemic.

PMID- 15469169
TI  - Hydatid disease in the breast: a case report.
AB  - A case of primary breast hydatid disease observed in a 42-year old female patient
      is reported. Physical examination, mammography and ultrasonography were the
      methods used for the diagnosis. The lesion was located in the upper outer
      quadrant of the right breast. The mass was surgically removed under local
      anaesthesia. No complications were observed postoperatively. We wanted to
      emphasize the importance of keeping in mind the possibility of hydatid disease in
      cystic breast lesions, particularly in endemic regions.

PMID- 15469170
TI  - Apocrine adenocarcinoma of the nipple: a case report.
AB  - Apocrine adenocarcinoma of the skin is a rare and, most of the time, clinically
      misdiagnosed malignant adnexal tumour. A 66-year-old female patient presented
      with an asymptomatic swelling of the left nipple that on pathological evaluation
      was confirmed as an apocrine adenocarcinoma. Surgery is to be considered as the
      mean treatment for such a lesion and the diagnosis is always difficult to
      establish. To our best knowledge, this is only the second reported apocrine
      adenocarcinoma arising from a nipple and the first presenting with Paget's
      phenomenon.

PMID- 15469171
TI  - Doctors at WAR, responsible surgeons: reflections on a ongoing debate. Comment on
      the publication "Doctors at War. Hospital medecine in Belgium (F. Dewallens,
      Acta. Chir. Belg. 2004, 104: 11-17).

PMID- 15469172
TI  - [Correlation between follicle levels of superoxide dismutase and oocyte quality,
      fertilization rates and embryo development].
AB  - BACKGROUND: The intraovarian oxidative balance is important during oocyte
      development, and fertilization. It has been proposed that one of the most
      important enzymes in the follicle is the superoxide dismutase (SOD). OBJECTIVE:
      To correlate levels and percentage of SOD activity in follicular liquid with
      quality, fertilization and embryo development in a group of patients submitted to
      in vitro fertilization. MATERIAL AND METHODS: We obtained 120 follicular liquids
      from oocytes aspirated in 41 patients during an IVF program and then we followed
      the development of each oocyte separately. We measured the activity and
      concentration of SOD in the follicular liquid, and we evaluated the following
      variables: quality and maturity in the oocytes, as well as fertilization rate,
      segmentation rate and pregnancy. The statistical analysis was made with ANOVA
      test and Pearson test. RESULTS: In the analysis of the results, we observed a
      higher percentage of activity in the SOD in oocytes with good quality (3 and 4)
      in comparison with poor quality oocyte (1 and 2) (89 and 82% vs 75 and 61%
      p<0.05). We observed higher concentrations and activity of SOD in oocytes with a
      good fertilization rate and segmentation (p<0.05). When we analyzed the variables
      in function of pregnancy, we observed that the embryos that were transferred and
      developed pregnancy had higher concentrations and activity of SOD than embryos
      that did not develop pregnancy. CONCLUSIONS: Elevated levels and high percentage
      in the activity of SOD are associated with a better quality in the oocyte, and a
      good embryo development, influenced by the oxidative balance.

PMID- 15469173
TI  - [Craniopharyngioma and its impact upon human reproduction: analysis of 15 cases
      at the Hospital Juarez de Mexico].
AB  - BACKGROUND: Craniopharyngiomas are intracranial tumors of non-glial origin
      derived from cellular remnants of the Rathke's pouch. Their frequency is 1-3% of
      intracranial tumors and 13% of suprasellar neoplasms. Histologically, it is a
      benign lesion, albeit clinically severe with a high index of relapse and sequelae
      upon the reproductive function. OBJECTIVE: To identify the clinical
      characteristics of patients with craniopharyngiomas before and after treatment.
      MATERIAL AND METHODS: We reviewed our experience of 15 cases with
      craniopharyngioma seen at the Hospital Juarez de Mexico from 1995 throughout
      2002. RESULTS: Prevalence was higher in males (ratio 2:1) with ages between 6-45
      years old (X 17.9 +/- 6.45 years). The most common symptoms were cephalalgia
      (100%) and visual disorders (93%); the average levels of hormonal determination
      were in females: FSH 1.0 mIU/mL, LH 0.5 mIU/mL, estradiol 11.0 pg/mL, PRL 80
      mg/mL. In males: FSH 1.7 mIU/mL, LH 2.6 mIU/mL, testosterone 0.6 mg/dL and PRL 29
      mg/mL. All patients had hypogonadotropic hypogonadism. Tumoral relapse was mostly
      seen in patients who underwent only surgery (n = 7, 46.6%). The ones with surgery
      and radiotherapy (n = 8, 53.3%) did not disclose symptoms that required another
      surgery. CONCLUSIONS: The main repercussion of craniopharyngioma, due to its
      proximity to hypothalamus and hypophysis, is on the endocrine and reproductive
      areas of human being.

PMID- 15469174
TI  - [Absence of antiosteopenic effect of hormone replacement therapy in
      postmenopausal women].
AB  - BACKGROUND: Several studies suggest that hormone replacement therapy (HRT) stops
      bone loss in postmenopausal women while increasing their bone mineral density up
      to 20%; however, there are studies where hormone replacement therapy does not
      increase bone density, only prevents it. OBJECTIVE: To analyze the effect of
      hormone replacement therapy upon bone mineral density of hip and lumbar spine in
      postmenopausal women. MATERIAL AND METHODS: Clinical files of several patients
      with sudden menopause diagnosis seen at the Hospital Juarez of Mexico were
      reviewed in the year 2000. They received hormone replacement therapy of
      conjugated estrogens and medroxyprogesterone acetate, with annual controls of
      estradiol in blood, equal or higher than 50 pg/mL and bone mineral density
      measurement (BMD) with DEXA (dual energy X-ray absortiometry) central (hip and
      lumbar spine), and at least one control within a period of four years. 89
      patients were included and four groups were determined: all of them had basal
      densitometry in one (group 1), two (group 2), three (group 3), and four years
      (group 4) of monitoring. The percentage of bone mineral density was calculated in
      both anatomic areas and per group. In each study group the number or patients
      that showed gain, loss or whose mineral bone density stayed the same was
      assessed. The statistical analysis was made using the Student t test. RESULTS:
      The 89 patients mean age was of 50.5 (SD +/- 6.42) years. All of them showed
      spontaneous menopause. The average time of menopause evolution was of 6.9 (SD +/-
      4.7) years. The body mass index (BMI) average was of 27.5 (SD +/- 3.97) kg/m2.
      After admittance, all patients received hormone replacement therapy with
      conjugated equine estrogens (0.625 mg and medroxyprogesterone acetate 2.5
      mg/day). A gain of bone mineral density in the second and third year of treatment
      in the left hip and in the lumbar spine was observed; however, there were no
      important differences in any study group when results were treated statistically.
      CONCLUSION: Hormone replacement therapy was not effective to prevent bone loss,
      neither to increase bone density. Only one treatment was tested, and might be
      necessary to investigate the effect of other routes of administration or
      formulations.

PMID- 15469175
TI  - [Genital prolapse].
AB  - Genital prolapse refers to a pelvic organ protrusion toward or out of the vaginal
      canal as a consequence of the sustenance system's failure of pelvic organs. The
      objective of exploration is to diagnose the specific site of the defect causing
      prolapse, which gives place to the classification and determination of the most
      proper treatment. This paper reviews concepts related to symptoms and diagnosis
      of genital prolapse.

PMID- 15469176
TI  - [Infertility due to a pituitary gangliocytoma].
AB  - This tumor of hypophyseal origin is rare and its incidence is estimated from 2-5%
      of central nervous system neoplasms. It is characterized by enlargement of the
      sella turcica and by the presence of neuron with adenomatous tissue since it is
      derived form the neural crest. Clinical symptoms do not differ from pituitary
      adenomas. The diagnosis is made by histological analysis and prognosis is
      favorable after surgical excision. It is reported the case of a 27 year old
      female complaining of abnormal menses who was seen at our clinic due to primary
      infertility of 6 year duration and galactorrhea. An MRI disclosed a 7 mm lesion
      within the pituitary area. Prolactin was 167 ng/mL. The patient underwent
      transphenoidal surgery and the histological report was of gangliocytoma. Two
      months after surgery the patient resumed menses and 6 months later a MRI did not
      reveal residual tumor; prolactin levels decreased to 44.8 and 18 ng/mL.
      Afterwards, the patient became pregnant and had a normal delivery. To our
      knowledge this is the first report of infertility due to a pituitary
      gangliocytoma.

PMID- 15469177
TI  - [Myocardial infarction during puerperium. A case report and literature review].
AB  - The incidence of acute myocardial infarction related to pregnancy is of 10,000;
      it is less frequent during puerperium, since only 24 cases have been reported in
      literature. A young woman, without coronary risk factors, presented a myocardial
      infarction in the immediate puerperium.

PMID- 15469178
TI  - [Treatment of male sterility. 1949].

PMID- 15469179
TI  - [Specific recommendations for avoiding bad practice in neonatology].

PMID- 15469180
TI  - Proctalgia plus.

PMID- 15469182
TI  - To err is human, but patient safety requires correcting medical errors.

PMID- 15469183
TI  - Presidential address. George E. McGee MD.

PMID- 15469184
TI  - The country surgeon and his nurse in 1904. 1904.

PMID- 15469185
TI  - The personal impact of schizophrenia in Europe.
AB  - The personal impact of schizophrenia is poorly described in the scientific
      literature. The European Psychiatric Services: Inputs Linked to Outcome Domains
      and Needs (EPSILON) study compared representative treated prevalence cohorts of
      patients with schizophrenia in five European countries, to assess unmet needs,
      impact on caregivers, quality of life, satisfaction with services, symptoms and
      disability. Of the 404 patients, 79% undertook no work of any kind, and 65% were
      single. Low quality of life was associated with: anxiety, depression, psychotic
      symptoms, more previous psychiatric admissions, alcohol abuse, having no reliable
      friends nor daily contact with family, being unemployed, and having few leisure
      activities. The most frequently occurring unmet needs among the patients were:
      daytime activities, company and intimate relationships, psychotic symptoms,
      psychological distress, and information. The most common worries of relatives
      were about the patient's health, and their own future, safety and financial
      position. Psychiatric services were therefore largely ineffective in managing the
      personal impact of schizophrenia, especially upon work, home and family life.
      Research, clinical practice and disability policy developments need to address a
      wider range of consequences of the disorder than symptoms alone.

PMID- 15469186
TI  - The sociodemographic correlates of schizophrenia in Butajira, rural Ethiopia.
AB  - OBJECTIVES: To describe the major sociodemographic correlates of schizophrenia,
      and their interactions, in a rural population of Ethiopia. METHODS: We have
      recently completed a study in Butajira to identify cases of major mental
      disorders for description of course and outcome. A total of 318 cases of
      schizophrenia were identified by a door-to-door survey of a predominantly rural
      population of close to 68,500 individuals. Cases were confirmed by use of the
      SCAN and clinical assessment. FINDINGS: The study showed that being male, under
      35 years of age, unmarried, educated and living in an urban area were factors all
      associated with schizophrenia independently of each other. The risk of
      schizophrenia associated with being male was much higher in those aged 35 and
      over compared to those under 35 years of age. The risk of schizophrenia among
      males was higher in those not married (never married, separated, divorced or
      widowed) compared to those who were married. The association of marital status
      with schizophrenia was also more pronounced among those aged 35 year or over
      compared to those under 35. The association between schizophrenia and being
      unmarried was higher in urban than in rural areas. CONCLUSION: The
      sociodemographic correlates of schizophrenia in this rural population were
      similar to those described for the developed world. Furthermore, there were
      significant interactions between sex, age, marital status, area of residence and
      education as correlates of schizophrenia.

PMID- 15469187
TI  - Premorbid adjustment and violent behavior in schizophrenic patients.
AB  - We examined the influence of premorbid adjustment on violent behavior in
      schizophrenic patients. There is some evidence that poor premorbid adjustment
      predicts violent behavior, then we decided to examine this hypothesis further.
      METHOD: We recruited 72 schizophrenic patients without concomitant substance
      abuse 6 months prior to the assessment. Diagnoses were based on the SCID-I.
      Premorbid adjustment was evaluated with the Premorbid Adjustment Scale and
      violent behaviors with the Overt Aggression Scale. RESULTS: Violent schizophrenic
      patients showed an overall worse premorbid adjustment during childhood. In
      addition, the area of "peer relationships" was significantly diminished in
      several life period sections such as childhood, early and late adolescence in
      violent patients. DISCUSSION: Our data indicate that difficulties in social
      relationships during early stages of life may increase the risk of future violent
      behavior among schizophrenic patients.

PMID- 15469188
TI  - Layer upon layer: thermoregulation in schizophrenia.
AB  - A review of the relevant published literature regarding disorders of
      thermoregulation in people with schizophrenia was undertaken. This entailed a
      search of the Medline and PsychINFO databases to 28th May 2003 using the search
      terms "schizophrenia and thermoregulation" and "schizophrenia and temperature".
      The relevant articles as well as secondary references were reviewed. It has
      generally been shown that, when compared with controls, people with schizophrenia
      exhibit dysregulation of body temperature including different baseline
      temperatures; abnormal daily range of temperatures and diurnal variation showing
      an earlier peak; an impaired ability to compensate to heat stress; and
      compensating more effectively to cold stress. This may be intrinsic to the
      syndrome of schizophrenia but is potentially confounded by the administration of
      neuroleptic medication. The underlying cause is likely to be a combination of
      "peripheral" and "central" mechanisms of thermoregulation. Further study is
      required to delineate clearly the quality and magnitude of the temperature
      dysregulation as well as elucidating its mechanism(s). This could further our
      understanding of the mechanism underlying the syndrome of schizophrenia.

PMID- 15469189
TI  - Spatial and temporal parameters of gait disturbances in schizophrenic patients.
AB  - This study assessed the locomotor patterns of gait in schizophrenic patients and
      differentiated intrinsic effects of the illness from those caused by conventional
      and atypical neuroleptic treatment. Gait parameters of drug-naive, conventionally
      and atypically treated patients as well as control subjects were evaluated.
      Differences in gait velocity and in stride length between the four investigated
      groups were highly significant (ANOVA: p<0.001). Mean gait velocities of all
      patient groups were significantly slower than those of controls, with the most
      striking difference observed between the control group and patients treated with
      conventional neuroleptics (p <0.001). Amongst the patient groups, significant
      differences were detected between patients treated with conventional neuroleptics
      and both patients treated with atypical neuroleptics and drug-naive patients (p <
      0.05), but not between untreated and atypically treated patients. In all patient
      groups the reduction of gait velocity was due to a smaller mean stride length,
      while the cadence (steps per minute) was not changed. These results indicate that
      schizophrenia causes a primary disturbance of stride length regulation.
      Conventional antipsychotic treatment intensifies this deficit, whereas atypical
      antipsychotic treatment does not cause any additional gait disturbances. In
      contrast to the spatial parameters, the temporal structure of schizophrenic gait
      is not affected either by antipsychotic treatment or schizophrenia itself.

PMID- 15469190
TI  - Early life stress and PTSD symptoms in patients with comorbid schizophrenia and
      substance abuse.
AB  - OBJECTIVE: The comorbidity of schizophrenia and substance abuse is well
      documented and is remarkable for its prevalence and poor prognosis. While the
      etiology for this association is unknown, one possible mechanism relates to
      traumatic early life experiences, which have been shown to predispose individuals
      to both psychosis and substance abuse. METHODS: Participants (N=122) who were
      outpatients in an inner city public mental health clinic and who were diagnosed
      with schizophrenia, were administered a battery of structured clinical
      assessments including the Childhood Traumatic Events Scale (CTES), Davidson PTSD
      rating scale, Hamilton Depression Rating Scale (HDRS), Positive and Negative
      Symptom Scale (PANSS), and assessments of medication satisfaction and side
      effects. Patients with schizophrenia and a history of substance abuse (N=70) were
      compared to patients with schizophrenia who did not have a history of substance
      abuse (N=52). RESULTS: Patients with schizophrenia and a history of substance
      abuse had significantly higher frequency and severity of childhood traumatic
      events, greater PTSD symptomatology, significantly higher depression scores, and
      higher scores on the general subscale of the PANSS. DISCUSSION: Our findings lend
      support to the notion that sensitization to stress from early life experiences
      may be a factor contributing to the high rate of substance abuse comorbidity in
      patients with schizophrenia.

PMID- 15469191
TI  - Familiarity with mental illness and social distance from people with
      schizophrenia and major depression: testing a model using data from a
      representative population survey.
AB  - OBJECTIVES: The main purpose of this study is to examine whether the relationship
      between familiarity with mental illness and stigmatizing attitudes about mental
      illness, which had been observed in a previous study based on a sample of
      community college students (Psychiatr. Serv. 52 (2001) 953), can be replicated
      using data from a representative population survey. METHODS: In spring 2001, a
      representative survey was carried out in Germany (n=5025). A personal, fully
      structured interview was conducted which began with the presentation of a
      vignette depicting someone with either schizophrenia or major depression.
      Respondents were asked to respond to measures assessing familiarity, perception
      of dangerousness, fear, and social distance. Path analysis with manifest variable
      structural modeling techniques was applied to test the model used in the previous
      study. RESULTS: Despite differences in methods, most findings of the previous
      study were replicated. Respondents who were familiar with mental illness were
      less likely to believe that people with schizophrenia or major depression are
      dangerous. Weaker perceptions of dangerousness corresponded closely with less
      fear of such people, which in turn was associated with less social distance. The
      effect of familiarity was somewhat pervasive: respondents who reported to be
      familiar with mental illness expressed a less strong desire for social distance.
      There is also a relatively strong relationship between perceived dangerousness
      and social distance. CONCLUSIONS: Our findings fully support the notion that
      approaches to social change which increase the public's familiarity with mental
      illness will decrease stigma.

PMID- 15469192
TI  - Age of menarche and schizophrenia onset in women.
AB  - OBJECTIVE: The "estrogen hypothesis" posits that this hormone serves as a
      protective factor in the development of schizophrenia. If true, then it is
      expected that the earlier the age of menarche, the later the onset of
      schizophrenia (as has been reported by some investigators). This study attempts
      to replicate this relationship in a sample of women with schizophrenia and
      schizoaffective disorder. METHOD: Self-report menarche age, clinical status, and
      onset of disorder were collected in a sample of 68 women (55 diagnosed with
      schizophrenia and 13 with schizoaffective disorder). RESULTS: Menarche age and
      schizophrenia onset were not negatively correlated as would be predicted by the
      estrogen hypothesis. Two clinical measures, however, did correlate with age of
      menarche as predicted. Higher negative symptom scores (total SANS) and greater
      functional impairment (lower GAF) were reported in subjects who reported a later
      age at menarche. CONCLUSION: This study suggests that an earlier age at menarche
      might predict improved clinical outcome after schizophrenia onset (in support of
      the estrogen hypothesis). Our data, however, do not support Cohen et al.'s
      findings regarding the relationship between age at menarche, and the timing of
      the onset of the disorder. Further investigations regarding the relationship
      between estrogen and schizophrenia development in women are needed. It is
      suggested that other developmental factors, both biological and psychosocial,
      might play a crucial role in both the age at onset and the outcome of the
      disorder in women.

PMID- 15469193
TI  - A polydiagnostic and dimensional comparison of epileptic psychoses and
      schizophrenia spectrum disorders.
AB  - After establishing the validity of the Japanese version of the Operational
      Criteria Checklist for Psychotic Illness (OPCRIT), we applied it to 58
      consecutive patients with epileptic psychoses (index group) and to age- and sex
      matched controls with schizophrenia spectrum disorders (control group). Compared
      with the control group, the index group had a low family history of
      schizophrenia, high premorbid personality disorder and unemployment, abrupt or
      acute onset of psychosis, good recovery with single or multiple episodes, and low
      deterioration from a premorbid level of function. From 9% to 52% of the index
      group and 38% to 84% of the control group were diagnosed with schizophrenia
      according to the operational criteria used. The percentages of patients diagnosed
      with schizophrenia based on various diagnostic criteria in the two groups were
      similar. In the index group, a diagnosis of schizophrenia was more commonly made
      among patients with inter-ictal psychosis than among those with post-ictal
      psychosis. An exploratory factor analysis identified five factor solutions of
      manic, negative, depressive, vegetative, and positive symptoms. Although positive
      and negative factor values were lower in the index group than in the control
      group, the two groups shared a similar factor profile. These results indicate
      that the difference in symptomatology between the two groups was quantitative
      rather than qualitative.

PMID- 15469194
TI  - Mismatch negativity potentials and cognitive impairment in schizophrenia.
AB  - Cognitive impairment in schizophrenia is an important predictor of clinical and
      social outcome. In this preliminary study, the correlation between cognitive
      status and deficits in mismatch negativity (MMN) generation was explored. The MMN
      response to tone duration deviants was recorded using a new stimulation protocol
      with continuously changing ('roving') standard stimuli in order to measure the
      effect of standard repetitions on MMN (memory trace effect). Cognitive status of
      the patient group (n=28) was assessed using neuropsychological screening. Healthy
      participants (n=20) served as age-matched comparison group. In patients, MMN
      amplitude in frontal electrodes as well as the MMN memory trace effect was
      diminished compared to controls. While both measures were inversely related to
      patient's age and disease severity, only the MMN memory trace effect was robustly
      correlated with the degree of neuropsychological impairment. This suggests that
      ERP measures of auditory system adaptability more appropriately characterise the
      pathophysiological processes underlying cognitive impairment in schizophrenia
      than static measures of ERP magnitude.

PMID- 15469195
TI  - Sex differences in prepulse inhibition deficits in chronic schizophrenia.
AB  - Recent years have seen a dramatic growth in the number of studies using prepulse
      inhibition (PPI) paradigms to index information processing deficits in
      schizophrenia. There are, however, robust sex differences in PPI in healthy
      subjects, with women exhibiting less PPI than men in the absence of any
      psychopathology. To investigate the role of sex in prepulse modification deficits
      in the long-term course of schizophrenia, we assessed PPI (response inhibition
      with the prepulse preceding the pulse by 30-150 ms) and prepulse facilitation
      (PPF; response facilitation with the prepulse preceding the pulse by 1000 ms) of
      the acoustic startle response in 42 chronic schizophrenia patients (27 men; all
      42 on typical antipsychotics) and 35 controls (15 men). The results revealed that
      healthy women showed less PPI than healthy men. Men with schizophrenia showed
      less PPI compared to healthy men, but women with schizophrenia did not differ in
      PPI from healthy women. Age of illness onset negatively correlated to PPI in male
      patients. There was no significant effect of sex in PPF, and although patients
      (regardless of sex) showed less PPF relative to controls, this effect was
      abolished when the current age was co-varied for. These findings indicate sex
      differences in PPI deficits in schizophrenia. Future studies of schizophrenia
      patients need to take sex and age of subjects into account to optimise the
      investigation of PPI deficits, and their clinical, neural, and pharmacological
      correlates.

PMID- 15469196
TI  - Thalamic dysfunction in schizophrenia: neurochemical, neuropathological, and in
      vivo imaging abnormalities.
AB  - While abnormalities of the prefrontal cortex and temporal lobe structures have
      typically been associated with the pathophysiology of schizophrenia, recent
      findings implicate thalamic dysfunction in this illness as well. The thalamus
      plays a critical role in processing and integrating sensory information relevant
      to emotional and cognitive functions. Neuropathological and in vivo imaging
      studies in schizophrenia have identified several structural and metabolic
      abnormalities in the thalamus, which may contribute to a deficit in sensory
      processing and be related to psychotic symptomatology. In addition to these
      postmortem and in vivo imaging studies indicating structural and metabolic
      changes in the thalamus in schizophrenia, more recent studies have examined the
      neurochemical substrates that accompany these changes. Much of this work to date
      has focused on glutamatergic abnormalities in the thalamus, in part because it is
      a predominant neurotransmitter used in the thalamus, and because glutamatergic
      dysfunction has been hypothesized to be involved in schizophrenia. Several
      studies, however, have also examined markers of gamma-aminobutyric acid (GABA)
      and dopaminergic neurotransmission in the thalamus in schizophrenia. We review
      these neurochemical findings, as well as the growing body of postmortem and in
      vivo imaging evidence that supports the hypothesis of thalamic dysfunction in
      schizophrenia.

PMID- 15469197
TI  - Widespread electrical cortical dysfunction in schizophrenia.
AB  - The purpose of this study was to compare slow cortical electrical activity
      between healthy and schizophrenic individuals using 123-channel EEG and current
      density reconstruction (CDR). Twenty-nine healthy subjects and 14 drug-free
      patients performed three visual paired-associate tasks (verbal, pictorial and
      spatial). We modeled the generators of the slow potentials (SPs) at their peak
      amplitude by Lp-norm minimization using individual MRIs to model the volume
      conductor and source. Activity in each architectonic area of Brodmann was scored
      with respect to individual maximum current by a percentile method. Resulting
      scores by cortical area were analyzed by multivariate analysis of variance
      (MANOVA) with planned comparisons, to search for differences among levels.
      Results showed a multifocal pattern of current density foci comprising the SP
      generators, including frontal and posterior cortices in all subjects. A few
      cortical areas, not exclusively frontal, were observed to significantly differ
      between groups. Moreover, changes in patients' frontal activity were not
      exclusively to lower scores or 'hipofrontality': overall effects (all tasks
      collapsed) included increased electrical activity in right area 10, left 38 and
      47 bilaterally, and decreased activity in right area 6 and left areas 39, 21 and
      19. A few additional areas showed significantly altered activity only in
      particular tasks. We conclude that the present method, by preserving individual
      anatomical and functional information, indicates bidirectional patterns of
      altered electrical activity in specific cortical association areas in
      schizophrenia, which are not compatible with the exclusive 'hipofrontality'
      hypothesis. Our results agree with the hypothesis of schizophrenia as a syndrome
      resulting from abnormalities in multiple encephalic foci.

PMID- 15469198
TI  - What is measured by verbal fluency tests in schizophrenia?
AB  - INTRODUCTION: Schizophrenia patients perform below the norm on verbal fluency
      tests. The causes for this are unknown, but defective memory, executive
      functioning and psychomotor speed may play a role. METHOD: We examined 50
      patients with schizophrenia and related disorders, and 25 healthy controls with a
      cognitive test battery containing tests for verbal memory, executive functioning
      and psychomotor speed, and a categorical fluency test. RESULTS: Patients obtained
      significantly lower test results than the controls on most cognitive measures
      including the verbal fluency test. During the fluency test, they formed as many
      clusters, and switched as often between clusters as the controls did, but they
      generated fewer words per cluster. Interestingly, in the control group, fluency
      performance was predicted by memory and executive functioning, but not by
      psychomotor speed. In patients, verbal fluency was predicted by psychomotor
      speed, but not by memory or executive functioning. DISCUSSION: We conclude that
      psychomotor speed could be a crucial factor in cognition, and its influence on
      cognitive test performance should be considered in schizophrenia research.
      Furthermore, these data illustrate the importance of qualitative analysis of
      cognitive impairments in schizophrenia patients, as traditional cognitive tests
      often only provide quantitative information.

PMID- 15469199
TI  - Misattribution of external speech in patients with hallucinations and delusions.
AB  - BACKGROUND: One of the main cognitive models of positive symptoms in
      schizophrenia proposes that they arise through impaired self-monitoring. This is
      supported by evidence of behavioural deficits on tasks designed to engage self
      monitoring, but these deficits could also result from an externalising response
      bias. We examined whether patients with hallucinations and delusions would
      demonstrate an externalising bias on a task that did not involve cognitive self
      monitoring. METHOD: Participants passively listened (without speaking) to
      recordings of single adjectives spoken in their own and another person's voice,
      and made self/nonself judgements about their source. The acoustic quality of
      recorded speech was experimentally manipulated by altering the pitch. Fifteen
      patients with schizophrenia who were currently experiencing hallucinations and
      delusions, 13 patients with schizophrenia not experiencing current hallucinations
      and delusions and 15 healthy controls were compared. RESULTS: When listening to
      distorted words, patients with hallucinations and delusions were more likely than
      both the group with no hallucinations and delusions and the control group to
      misidentify their own speech as alien (i.e. spoken by someone else). Across the
      combined patient groups, the tendency to misidentify self-generated speech as
      alien was positively correlated with current severity of hallucinations but not
      with ratings of delusions or positive symptoms in general. CONCLUSIONS: These
      findings indicate that patients with hallucinations and delusions are prone to
      misidentifying their own verbal material as alien in a task which does not
      involve cognitive self-monitoring. This suggests that these symptoms are related
      to an externalising bias in the processing of sensory material, and not solely a
      function of defective self-monitoring.

PMID- 15469200
TI  - Assessment of executive dysfunction during activities of daily living in
      schizophrenia.
AB  - Many neuropsychological studies have described deficits of memory and executive
      functions in patients with schizophrenia, and the severity of these deficits
      seems to be determinant in predicting the community outcome of these patients
      [Schizophr. Bull. 26 (2000) 119]. However, neuropsychological evaluation does not
      provide valuable information about how the cognitive deficits directly affect
      daily living, that is, which cognitive deficit affects which behavior. The
      present study aimed at determining whether executive dysfunction in schizophrenia
      could be directly measured by analyzing three activities of daily living (ADL),
      in addition to assessing the ecological validity of commonly used
      neuropsychological tests. Within specific ADL (choosing a menu, shopping the
      ingredients, cooking a meal), the sequences of behaviors that have been performed
      by 27 control subjects and 27 patients with schizophrenia were both analyzed by
      using a preset optimal sequence of behavior. When compared with control subjects,
      patients with schizophrenia showed more omissions when choosing the menu, more
      sequencing and repetitions errors during the shopping task, and more planning,
      sequencing, repetition and omission errors during the cooking task. These
      behavioral errors correlated significantly with negative, but not with positive
      symptoms of the patients. Furthermore, they also correlated with the poor
      performances on executive neuropsychological tests, especially those sensitive to
      shifting and sequencing abilities, but not with memory tests. These results
      suggest that executive deficits in schizophrenia may specifically affect ADL and
      that such deficits can be quantitatively assessed with a behavioral scale of
      action sequences.

PMID- 15469201
TI  - No association of the T102C polymorphism of the serotonin 2A receptor gene
      (HTR2A) with suicidality in schizophrenia.
AB  - Additional evidence for a role of serotonin (5-HT) in the pathogenesis of
      suicidal behavior is provided by a recent report that the 5-HT2A (HTR2A) T102C
      polymorphism was associated with suicidality in patients with major depression.
      Three other studies have, however, failed to find an association between this
      polymorphism and suicidality in major depression. The goal of the present study
      was to test the association of allele C of T102C HTR2A polymorphism with
      suicidality in patients with schizophrenia or schizoaffective disorder. Seventy
      one patients with DSM-III-R diagnosis of schizophrenia or schizoaffective
      disorder were included in the study. Patients were genotyped for the T102C HTR2A
      polymorphism. Information about lifetime suicidality was obtained during the
      course of SADS interviews. In addition, current suicidality was assessed by the
      Hamilton Depression Scale in 46 patients. There were no significant differences
      in allele frequencies and genotype distributions between suicidal and non
      suicidal patients using lifetime or current suicidality measures. The results of
      this study did not demonstrate a robust association of the allele C of the T102C
      HTR2A polymorphism with lifetime or current suicidality in patients with
      schizophrenia. However, the mean Hamilton Depression Scale item for current
      suicidality was significantly higher in patient with genotype T/C compared to
      those with genotype C/C (p = 0.01) and marginally higher than for the patients
      with genotype T/T (p=0.06). The relatively small sample size suggests a study
      with a larger sample and greater power would be of interest.

PMID- 15469202
TI  - Psychosocial functioning on the Independent Living Skills Survey in older
      outpatients with schizophrenia.
AB  - Improving real-life community functioning in patients with severe mental illness
      has been an important recent focus of treatment outcome research. Few studies,
      however, have examined psychosocial functioning in older psychotic patients. The
      Independent Living Skills Survey (ILSS) is a measure of the basic functional
      living skills of individuals with severe and persistent mental illness. The self
      report version of the ILSS was administered to 57 middle-aged and older community
      dwelling outpatients with schizophrenia and 40 age-comparable nonpsychiatric
      participants. Regardless of whether patients resided in assisted living or
      independent settings, they showed significantly impaired functioning on a
      majority of the functional areas assessed by the ILSS. No consistent relationship
      was found between symptom severity and functioning. With certain modifications,
      the ILSS appears to be a sensitive indicator of functional impairment in this
      older sample of community-dwelling outpatients with schizophrenia. Information
      provided by the instrument might be useful to guide rehabilitation efforts and
      measure functioning changes in response to treatment in this population.

PMID- 15469203
TI  - Glial fibrillary acidic protein is reduced in cerebellum of subjects with major
      depression, but not schizophrenia.
AB  - Glial fibrillary acidic protein (GFAP) is a major protein of astrocyte
      intermediate filaments and a specific marker for astrocytes. Alterations in
      levels of GFAP may reflect pathological regulation of neuronal function and
      survival as well as abnormal synaptogenesis and neurotransmission. We employed
      quantitative gel electrophoresis and Western blotting to measure levels of GFAP
      in cerebella of 60 subjects divided equally among schizophrenia, bipolar
      disorder, major depression, and normal controls. GFAP levels were reduced by 32%,
      17% and 14.5% in depressed, bipolar, and schizophrenic cerebella, respectively,
      versus controls. Only the depressed value was significantly different (p=0.015
      Post-hoc Bonferroni test). Measurement of beta-actin levels showed no differences
      between the various groups. No significant effects of confounding variables were
      found. This is the first demonstration of GFAP reductions in cerebellum of
      subjects with mood disorders and schizophrenia, thereby adding to the reports of
      reductions in GFAP/glial cell counts in other brain regions of subjects with
      major depression, thus suggesting a downregulation of glial function in this
      disorder.

PMID- 15469204
TI  - Quetiapine in hospitalized patients with schizophrenia refractory to treatment
      with first-generation antipsychotics: a 4-week, flexible-dose, single-blind,
      exploratory, pilot trial.
AB  - This short-term, single-blind, pilot trial was initiated to investigate the
      usefulness of quetiapine therapy in the treatment of schizophrenic patients
      refractory to first-generation antipsychotics. Following a neuroleptic-free
      period prior to study entry (at least 1 week for oral formulations and 6 weeks
      for depot formulations), quetiapine was started at 50 mg/day and titrated up to
      500 mg/day by Day 6. This 500 mg daily dose was then maintained or increased up
      to a maximum of 750 mg/day, at the discretion of the treating physician, who was
      aware of the antipsychotic prescribed. Efficacy measures were represented by
      changes in total and component PANSS score from baseline to different intervals.
      Safety and tolerability were evaluated by monitoring the spontaneously referred
      moderate-to-severe adverse events, changes from baseline in SAS, BARS, and AIMS
      scores, supplementary use of flurazepam, lorazepam, and benztropine, clinically
      relevant physical changes, abnormalities in vital signs, blood chemistry, and
      hematology, and modifications in QTc interval and body weight. Rating scale
      assessments, categorization of adverse events, determination of physical
      examination, vital signs, and body weight were performed by a qualified physician
      blind to the particular antipsychotic under investigation and the aims of the
      study. All 12 patients completed the 4-week quetiapine treatment course. Mean
      total PANSS scores were significantly reduced between baseline and study endpoint
      (p=0.006). Five out of six PANSS subcomponent scores also showed significant
      decreases (p < 0.05). Six patients showed a reduction of > or = 20% in PANSS
      total score by the final day of quetiapine treatment, so were classified as
      responders. There were responders in all schizophrenia diagnostic subgroups
      (undifferentiated, paranoid, and disorganized). Two patients reported moderate
      adverse events. One patient received 3 days of benztropine therapy for EPS and
      five received flurazepam for insomnia. Weight change was minimal and mean SAS,
      BARS, and AIMS scores all showed nonsignificant decreases between baseline and
      endpoint. The 50% quetiapine response rate reported here in refractory patients
      is comparable with those previously reported for other atypical antipsychotics in
      populations of both refractory and intolerant patients.

PMID- 15469205
TI  - The timing of negative symptom exacerbations in relationship to positive symptom
      exacerbations in the early course of schizophrenia.
AB  - Although positive and negative symptoms appear to represent independent symptom
      dimensions of psychopathology when evaluated cross-sectionally among individuals
      with schizophrenia, it is not known if exacerbations of symptoms on these two
      dimensions are independent. This prospective longitudinal study examined the
      temporal relationship between the positive and negative symptom exacerbations
      among 48 recent-onset schizophrenia or schizoaffective patients who received
      symptom ratings every 2 weeks on the Brief Psychiatric Rating Scale. Patients
      were followed for a period of at least 1 year and a mean of 3 years. To examine
      the temporal relationship between positive and negative symptoms, six time
      periods were defined in relation to psychotic exacerbation or relapse (e.g.,
      prodromal, concurrent, post-psychotic) and used to compare the timing of positive
      and negative symptom exacerbations. A substantial proportion of patients had
      exacerbations of positive symptoms (77%) and negative (42%) symptoms. Negative
      symptom exacerbations occurred simultaneously with positive symptom exacerbations
      to a significantly greater extent than expected by chance, and occurred less
      frequently than expected by chance during the time period most temporally removed
      from positive symptom exacerbations. Results suggest that the timing of some
      negative symptom exacerbations is linked to that of positive symptom
      exacerbations during the early course of schizophrenia.

PMID- 15469206
TI  - Self-efficacy and neurocognition may be related to coping responses in recent
      onset schizophrenia.
AB  - Although stressful life events can trigger psychotic and depressive symptom
      exacerbation in schizophrenia, many patients who experience stressful events do
      not subsequently relapse. Models of vulnerability, stress, and protective factors
      in schizophrenia suggest that effective coping responses may serve as protective
      factors. Coping behavior, in turn, may be influenced by a schizophrenia patient's
      level of self-efficacy and neurocognitive functioning. Using the Coping Responses
      Inventory, we examined how 29 recent-onset schizophrenia outpatients and 24
      demographically matched normal comparison subjects responded to a negative
      interpersonal life event. Approach oriented coping responses, such as "Think of
      different ways to deal with the problem" and "Make a plan of action and follow
      it," were used significantly more often by normal subjects (M=2.27) than by
      schizophrenia patients (M=1.89; p < 0.02). Among schizophrenia patients, greater
      use of approach, problem-focused coping strategies was associated with high self
      efficacy (r=0.55, p < 0.01) and better performance on a measure of sustained
      attention emphasizing perceptual processing (r=0.42, p < 0.05). Multiple
      regression indicated that self-efficacy and sustained attention accounted for 56%
      of the variance in the use of problem-focused coping, strategies by schizophrenia
      patients.

PMID- 15469207
TI  - Fine needle aspiration biopsy and molecular analysis in differential diagnosis of
      lymphoproliferative diseases of the orbit and eye adnexa.
AB  - The aim of the investigation was the assessment of the role of routine cytology
      and clonality evaluation using PCR in differential diagnosis of
      lymphoproliferative diseases of the orbit and eye adnexa. The investigations were
      carried out in cellular material collected via fine needle aspiration biopsy
      (FNAB) from 29 patients aged 31-82 years, including 17 women and 12 men. Apart
      from routine cytology, molecular-genetic studies were performed employing the PCR
      technique. In 21 cases histopathology was performed. In 2 patients, despite
      several attempts, FNAB failed to provide any diagnostic material for routine
      cytology. Based on cytology, non-Hodgkin's lymphoma was diagnosed in 11 patients
      and suspected in three. In 13 patients no firm diagnosis was possible based on
      cytological smears. The employment of PCR allowed for rendering the diagnosis
      more precise in 13 cases, confirming it in 13 patients, while in 3 cases the
      results of the above tests did not affect the final diagnosis. Clonality studies
      by PCR may be performed in material obtained through FNAB. Clonality assessment
      by PCR technique is very useful in differential diagnosis of lymphoproliferative
      disordes.

PMID- 15469208
TI  - Benign vascular proliferations--an immunohistochemical and comparative study.
AB  - Hemangiomas constitute a heterogeneous group of benign vascular proliferations.
      Their pathogenesis is not completely understood. In this study the expression of
      GLUT-1, VEGF, Ki-67, bcl-2 and apoptotic index in twenty-six cases of infantile
      capillary hemangioma (ICH), fifteen of lobular capillary hemangioma (LCH) and
      nine of epithelioid hemangioma were examined. The expression of GLUT-1 was
      confined to ICH group and was completely absent in LCH and EH. The significant
      differences in the expression of VEGF, proliferative index and apoptosis between
      ICH, LCH, EH were found. The proliferative index and VEGF expression were highest
      in LCH. Apoptotic index was similar in LCH an ICH but negative in EH. The lesions
      examined did not differ significantly in bcl-2 expression. The GLUT-1 expression
      was not only Ki-67 but also apoptosis independent. Our findings might reflect the
      differences in biology and pathogenesis of hemangiomas.

PMID- 15469209
TI  - Diagnostic difficulties in pouchitis--experience from a single institution.
AB  - The aim of the study was to analyze the clinical, endoscopic and histological
      signs of pouchitis in patients operated on because of ulcerative colitis (UC) and
      familial adenomatous polyposis (FAP). Between 1984 and 2002, the Department of
      Surgery carried out 218 restorative proctocolectomies in patients with UC and 120
      in FAP patients. The follow-up to assess the intensity of inflammatory changes
      included 110 patients: 72 UC and 38 FAP. During the endoscopic examination,
      samples were taken for routine histological examinations. The histological
      assessment was based on the so-called Moskwitz's Histological System. Acute
      pouchitis is diagnosed if the score is > or =4, and chronic condition--if the
      score is > or =4. We used a modified PDAI scale to analyze the symptoms, taking
      into account the microscopically detectable histological features of chronic
      pouchitis. The clinical symptoms of pouchitis were revealed in 28 patients
      (25.5%), endoscopic symptoms in 36 patients (32.7%), and histological parameters
      in 48 patients (28-58.3% with > or =4 score of acute pouchitis and 20-41.7% with
      > or =4 score of chronic pouchitis). The signs of acute and chronic pouchitis
      were evident in endoscopy and histology, with no clinical features observed in
      many cases. Patients with symptoms of chronic pouchitis require a continuous
      follow-up.

PMID- 15469210
TI  - Thymoma with pseudosarcomatous stroma--an unusual variant of a slowly progressing
      thymic neoplasm.
AB  - The authors present the first Polish case of an extremely rare thymoma in a 70
      year old female surgical patient with 15-year observation before surgery.

PMID- 15469211
TI  - The historical outline of Vilnius pathological anatomy in the first half of the
      19th century.
AB  - The first post mortem examination was performed in Vilnius by a priest Stefan
      Bisio in 1770. At the end of the 18th century, Jakub Briotet, a surgeon and
      anatomist, founded a modest anatomical (surgery) study. In 1804, Jan Piotr Frank
      and his son Jozef arrived to Vilnius and became professors of the University. Jan
      Piotr Frank took charge of the University Teaching Hospital and Jozef of the
      Chair of Pathology. When, in 1805, Jozef Frank took charge, after his father, of
      the University Hospital, he founded the first anatomopathological examination
      room there. The samples were obtained mainly from post mortem studies--autopsies.
      Most of the samples kept in spirit in the Frank's room were eaten by the starving
      French soldiers during the retreat of Napoleon's army. Getting dead bodies for
      the Universities was easy thanks to Tsar's decrees from the years 1793-1809 which
      ordered to open dead bodies and collect monsters. Moreover, a permission to
      transfer dead bodies from military hospitals to the University was issued in
      1810. These decrees did not stop the cases of students digging out dead bodies
      from the graves, which still happened in 1810 and 1817. Jozef Frank acknowledged
      great role of post mortem in medicine teaching. He wrote: an author describing a
      disease with lethal outcome, who does not mention pathological changes found
      through autopsy is backward. Beside Frank's study, there was still a study
      founded by Briotet at the Vilnius University, at the Chair of Anatomy. In 1808,
      Tsar Alexander I designed ruins of Spaska Orthodox Church for an anatomic
      theater. After seven year redecoration works, it was opened. Beside the theater,
      dissection room and Veterinary Institute, the building included zoological,
      veterinary and anatomical museum. The growing anatomical museum had, in 1841,
      2895 preparations including 1239 anatomopathological preparations. After closing
      down Vilnius University and opening Medical and Surgery Academy, pathological
      anatomy classes were introduced for the 5th year students in 1834. The first
      lecturer of pathological anatomy, as an individual subject, was Ludwik Siewruk.
      He started the classes in 1840 when he took charge of the Chair of Anatomy at the
      Moscow University. Jan Leonow continued the classes till the closing down of
      Medical and Surgery Academy by the tsar in 1842. The classes performed by Siewruk
      and Leonow were limited to lectures. Practical knowledge, autopsies were a part
      of pathology classes and specific therapy (3rd and 4th years of studies). After
      the Academy had been closed down, all the exhibits of the Vilnius anatomical
      museum, including anatomopathological preparations were moved to the anatomical
      museum of Kiev University. Few of them remained in the Vilnius Medical Society.

PMID- 15469212
TI  - JWC/Tendra (Molnlycke) Scholarships: a progress report.

PMID- 15469213
TI  - Developing a tool to diagnose cases of necrotising fasciitis.
AB  - The rising incidence and high mortality of this soft-tissue disease means it is
      vital to make a speedy diagnosis. The study described in this paper set out to
      develop a protocol to aid clinicians to make a rapid diagnosis and initiate
      prompt treatment.

PMID- 15469214
TI  - The beneficial effect of motorised ankle dorsiflexion on the healing of diabetic
      foot ulcers.
AB  - Many people with diabetes develop foot ulcers which, in extreme cases, lead to
      digit amputation. A small trial of a new device that induces ankle dorsiflexion
      improved peripheral circulation and resulted in the complete healing of all
      ulcers.

PMID- 15469215
TI  - The effectiveness of oral nutritional supplementation in the healing of pressure
      ulcers.
AB  - OBJECTIVE: To investigate the effectiveness of an oral nutritional supplement
      that is rich in protein and enriched with arginine, vitamin C and zinc on the
      healing of pressure ulcers. METHOD: Thirty-nine patients with grade III or IV
      pressure ulcers were enrolled into this open intervention study. Subjects
      received an oral nutritional supplement daily for three weeks. Wound area and the
      wound condition of the ulcers were assessed weekly. RESULTS: After three weeks of
      supplementation, median wound area reduced significantly (p < 0.001) from 23.6
      cm2 (1.6-176.6 cm2) to 19.2 cm2 (1.2-132.7 cm2), a reduction of 29%. Median
      healing of wound area was 0.34 cm2 per day, taking approximately two days to heal
      1 cm2. Within three weeks the amount of exudate in infected ulcers (p = 0.012)
      and the incidence of necrotic tissue (p = 0.001) reduced significantly.
      CONCLUSION: Nutritional intervention in the form of a specific oral nutritional
      supplement resulted in a significant reduction in wound area and an improvement
      in wound condition in patients with grade III and IV pressure ulcers within three
      weeks.

PMID- 15469216
TI  - An Indian community-based epidemiological study of wounds.
AB  - OBJECTIVE: To establish the prevalence of wounds in a community, with an emphasis
      on chronic lower extremity wounds, and to identify the various aetiological
      factors involved. METHOD: A cross-sectional study was conducted to screen the
      population of two nearby communities (one urban and one rural) in India for
      wounds. This involved conducting a door-to-door survey between July 2001 and
      February 2003. RESULTS: The prevalence of wounds in the population studied (n =
      6917) was 15.03 per 1000. The prevalences of acute and chronic wounds were 10.55
      and 4.48 per 1000 of the population respectively. CONCLUSION: The most common
      site for both acute and chronic wounds was the lower extremity. In contrast to
      Western studies, the most common aetiology for a chronic lower extremity wound
      was an untreated acute traumatic wound. This in turn highlights the need to
      establish community-based wound-care teams in India.

PMID- 15469217
TI  - Patient repositioning revisited.
AB  - Everyone agrees that regular patient repositioning helps to prevent pressure
      ulceration. This paper describes the benefits and disadvantages, as cited in the
      literature, of the various patient positions used in clinical practice.

PMID- 15469218
TI  - Pressure ulcer prevention: nurses' knowledge, attitudes and behaviour.
AB  - Despite the increased expenditure on pressure ulcer prevention strategies,
      incidence and prevalence is increasing. Exploring nurses' attitudes about these
      programmes offers an insight into why, in some cases, they are not working.

PMID- 15469219
TI  - Spotlight on the World Union of Wound Healing Societies' meeting.
AB  - Given the strides made between the inaugural meeting of the World Union of Wound
      Healing Societies and the most recent one, held in Paris, there is little doubt
      it will go from strength to strength. Three symposia caught our editor's eye.

PMID- 15469220
TI  - Diagnosis, assessment and management of mixed aetiology ulcers using reduced
      compression.
AB  - Accurate diagnosis of mixed aetiology leg ulcers depends on detailed assessment
      by a trained practitioner. This paper, the fourth in a six-part series on leg
      ulcers, describes how reduced compression bandaging can achieve successful
      outcomes.

PMID- 15469221
TI  - An unusual complication of Vacuum Assisted Closure in the treatment of a pressure
      ulcer.
AB  - A patient with a non-healing sacral pressure ulcer underwent exploratory surgery.
      During the procedure a piece of polyurethane sponge was found to have been left
      in situ. This unusual case highlights the importance of vigilance at dressing
      changes.

PMID- 15469222
TI  - Use of topical negative pressure therapy in postoperative dehisced or infected
      wounds.
AB  - Animal and case studies suggest that topical negative pressure for subacute
      wounds can increase angiogenesis and local blood flow and reduce bacterial
      counts, but clinical trials into the technique have yet to be conducted.

PMID- 15469223
TI  - Hormone replacement therapy.

PMID- 15469224
TI  - New therapies in tendon reconstruction.
AB  - Despite the use of various types of grafts, no surgical treatment currently
      exists to restore a tendon to its normal condition. Tissue engineering techniques
      are being used to develop therapies for tendon reconstruction. Biologic and
      synthetic scaffolds can both repair tendon defects and improve healing by
      allowing for the regeneration of the tendon's natural biologic composition to
      restore its mechanical capacity. This process can be further enhanced through
      augmentation methods such as cell seeding, growth factor implantation, and gene
      therapy.

PMID- 15469225
TI  - Fibrous dysplasia.
AB  - Fibrous dysplasia is a developmental disorder of bone that can present in a
      monostotic or polyostotic form. Primarily affecting adolescents and young adults,
      it accounts for 7% of benign bone tumors. Many of the asymptomatic lesions are
      found incidentally; the remainder present with symptoms of swelling, deformity,
      or pain. Fibrous dysplasia has been associated with multiple endocrine and
      nonendocrine disorders and with McCune-Albright and Mazabraud's syndromes. The
      etiology remains unclear, but molecular biology suggests a mutation in the
      G(s)alpha subunit and activation of c-fos and other proto-oncogenes. Fibrous
      dysplasia has a characteristic radiographic appearance. Most cases do not require
      intervention, but those that do usually are managed surgically with curettage,
      bone grafting, and, in some cases, internal fixation. When some intervention is
      necessary but surgery is not practical, treatment is with bisphosphonates. The
      prognosis generally is good, although poor outcomes are more frequent in younger
      patients and in those with polyostotic forms of the disease. The risk of
      malignant transformation is low.

PMID- 15469226
TI  - Dislocation after total hip arthroplasty.
AB  - Dislocation is one of the most common complications after total hip arthroplasty
      (THA). Risk factors include neuromuscular and cognitive disorders, patient non
      compliance, and previous hip surgery. Surgical considerations that must be
      addressed include approach, soft-tissue tension, component positioning,
      impingement, head size, acetabular liner profile, and surgeon experience. Recent
      improvements in posterior soft-tissue repair after primary THA have shown a
      reduced incidence of dislocation. When dislocation occurs, a thorough history,
      physical examination, and radiographic assessment help in choosing the proper
      intervention. Closed reduction usually is possible, and nonsurgical management
      frequently succeeds in preventing recurrence. When these measures fail, first
      line revision options should target the underlying etiology. This most often
      involves tensioning or augmentation of soft tissues, as in capsulorrhaphy or
      trochanteric advancement; correction of malpositioned components; or improving
      the head-to-neck ratio. If instability persists, or if a primary THA repeatedly
      dislocates without a clear cause, a constrained cup or bipolar femoral prosthesis
      may be as effective as a salvage procedure.

PMID- 15469227
TI  - Fusion in posttraumatic foot and ankle reconstruction.
AB  - Despite appropriate acute treatment, many foot and ankle injuries result in
      posttraumatic arthritis. Arthrodesis remains the mainstay of treatment of end
      stage arthritis of the foot and ankle. An understanding of the biomechanics of
      the foot and ankle, particularly which joints are most responsible for optimal
      function of the foot, can help guide reconstructive efforts. A careful history
      and physical examination, appropriate radiographs, and, when necessary,
      differential selective anesthetic blocks help limit fusion to only those joints
      that are causing pain. Compression fixation, when possible, remains the treatment
      of choice. When bone defects are present, however, neutralization fixation may be
      necessary to prevent a secondary deformity that could result from impaction into
      a bone defect.

PMID- 15469228
TI  - The acutely dislocated knee: evaluation and management.
AB  - Acute knee dislocations are uncommon orthopaedic injuries. Because they often
      spontaneously reduce before initial evaluation, the true incidence is unknown.
      Dislocation involves injury to multiple ligaments of the knee, resulting in
      multidirectional instability. Associated meniscal, osteochondral, and
      neurovascular injuries are often present and can complicate management. The
      substantial risk of associated vascular injury mandates that vascular integrity
      be confirmed by angiography in all suspected knee dislocations. Evaluation and
      initial management must be performed expeditiously to prevent limb-threatening
      complications. Definitive management of acute knee dislocation remains a matter
      of debate; however, surgical reconstruction or repair of all ligamentous injuries
      likely can help in achieving the return of adequate knee function. Important
      considerations in surgical management include surgical timing, graft selection,
      surgical technique, and postoperative rehabilitation.

PMID- 15469229
TI  - Management of pediatric femoral shaft fractures.
AB  - Femoral shaft fractures are the most common major pediatric injuries managed by
      the orthopaedic surgeon. Management is influenced by associated injuries or
      multiple trauma, fracture personality, age, family issues, and cost. In addition,
      child abuse should be considered in a young child with a femoral fracture.
      Nonsurgical management, usually with early spica cast application, is preferred
      in younger children. Surgery is common for the school-age child and for patients
      with high-energy trauma. In the older child, traction followed by casting,
      external fixation, flexible intramedullary nails, and plate fixation have
      specific indications. The skeletally mature teenager is treated with rigid
      intramedullary fixation. Potential complications of treatment include shortening,
      angular and rotational deformity, delayed union, nonunion, compartment syndrome,
      overgrowth, infection, skin problems, and scarring. Risks of surgical management
      include refracture after external fixator or plate removal, osteonecrosis after
      rigid antegrade intramedullary nail fixation, and soft-tissue irritation caused
      by the ends of flexible nails.

PMID- 15469230
TI  - Free vascularized fibular grafts for reconstruction of skeletal defects.
AB  - Nourished by the peroneal vessels, the versatile free vascularized fibular graft
      can be transferred to reconstruct skeletal defects of the extremities. It may be
      combined with skin, fascia, muscle, and growth-plate tissue to address the needs
      of the recipient site. It may be cut transversely and folded to reconstruct the
      length and width of tibial or femoral defects. The main indications for this
      graft are defects larger than 5 to 6 cm or with poor vascularity of the
      surrounding soft tissues. Detailed preoperative planning, experience in
      microvascular techniques, and careful postoperative follow-up are necessary to
      minimize complications and improve outcome. The free vascularized fibular graft
      has been successfully applied as a reconstruction option in patients with
      traumatic or septic skeletal defect, after tumor resection, and has shown promise
      in patients with congenital pseudarthrosis.

PMID- 15469231
TI  - Site-selective conjugation of thiols with aziridine-2-carboxylic acid-containing
      peptides.
AB  - The synthesis and convergent site-selective conjugation of aziridine-2-carboxylic
      acid-containing peptides with thiols, both in solution and on solid support, are
      described. The synthesis and use of FmocAzyOH in this capacity demonstrate both
      the efficient incorporation and tolerance of the Azy moiety in multistep Fmoc
      solid-phase peptide synthesis (SPPS), as well as the competence of solution and
      on-bead ligation through a highly regioselective base-promoted aziridine ring
      opening process.

PMID- 15469232
TI  - Bulk synthesis of polypyrrole nanofibers by a seeding approach.
AB  - The morphology of doped polypyrrole.Cl powder changes dramatically from granular
      to nanofibrillar when a very small amount (1-4 mg) of V2O5 nanofibers are added
      to a chemical oxidative polymerization of pyrrole in aq 1.0 M HCl using
      (NH4)2S2O8 as the oxidant. Unlike the polyaniline system, a key synthetic
      requirement in the polypyrrole system is for the seed template to be "active",
      i.e., to be capable of independently oxidizing the pyrrole monomer. Thin,
      strongly adherent films can be obtained on inert surfaces such as glass,
      plastics, etc., directly from the polymerization mixture without any bulk product
      isolation steps, significantly simplifying the processing of these nanofibers.

PMID- 15469233
TI  - Heme/Cu/O2 reactivity: change in FeIII-(O2 2-)-CuII unit peroxo binding geometry
      effected by tridentate copper chelation.
AB  - A new heme-peroxo-copper complex structural type with mu-eta2:eta2 peroxo
      ligation has been generated utilizing a heterobinucleating ligand with bis(2-(2
      pyridyl)ethyl)amine tridentate chelate for copper. Oxygenation of [(2L)FeIICuI]+
      (1) at -80 degrees C in CH2Cl2/6%EtCN, 1 (lambdamax, 426, 530 nm) produces
      [(2L)FeIII-(O22-)-CuII)]+ (3) (lambdamax, 419, 488, 544, 575 nm). Stopped-flow
      kinetic/spectroscopic probing reveals that a superoxo complex, [(2L)FeIII-(O2
      )...CuI(NCEt)]+ (2) (lambdamax = 544 nm), initially forms, k1 = 5.23 +/- 0.09 x
      104 M-1 s-1 (-105 degrees C). Subsequent intramolecular reaction of the copper(I)
      ion in 2 occurs with k2 = 2.74 +/- 0.04 x 101 s-1 (-105 degrees C), producing 3.
      Resonance Raman spectroscopy (rR) confirms the peroxo assignment for 3; nu(O-O) =
      747 cm-1 (Delta(18O2) = -40 cm-1). In an 16O-18O mixed isotope experiment a
      single band is observed at 730 cm-1. The low nu(O-O) value and the absence of a
      splitting of the 730 cm-1 band are indicative of a symmetrical binding of the
      peroxide group in a side-on mu-eta2:eta2 geometry. This conclusion is supported
      by X-ray absorption spectroscopy on 3. Copper K-edge EXAFS indicates a five
      coordinate metal center: 2 N, 2.028(7) A; 2 O, 1.898(7) A; 1 N, 2.171(12) A. An
      outer-sphere Fe scatterer is found at 3.62(1) A. The iron center K-edge EXAFS
      fits to either a five- or six-coordinate metal center: 4 N(pyrrole),
      approximately 2.1 A; 1,2 O, approximately 1.9 A. A preedge feature (Fe(1s) -->
      Fe(3d) transition) at 7113.2(2) eV resembles that obtained for a eta2-peroxo
      ferric heme complex, being weaker and at approximately 1.5 eV lower energy than
      those found in five-coordinate (P)FeIII-X (in C4v symmetry) complexes. Arguments
      based on rR properties of relevant peroxo compounds also effectively point to the
      copper(II) ion in 3 as being side-on bound, leading to the very low O-O
      stretching frequency observed in comparison to those of heme-peroxo species or
      heme-peroxo-copper complexes with a tetradentate copper chelate. These
      investigations derive from interest in establishing relevant and/or fundamental
      O2 chemistry at heme-copper centers, in relation to heme-copper oxidase active
      site chemistry.

PMID- 15469234
TI  - One-electron oxidation of a hydrogen-bonded phenol occurs by concerted proton
      coupled electron transfer.
AB  - The hydrogen-bonded phenol 2-(aminodiphenylmethyl)-4,6-di-tert-butylphenol (HOAr
      NH2) was prepared and oxidized in MeCN by a series of one-electron oxidants. The
      product is the phenoxyl radical in which the phenolic proton has transferred to
      the amine, *OAr-NH3+. The reaction of HOAr-NH2 and tris(p-tolyl)aminium
      ([N(tol)3]*+) to give *OAr-NH3+ + N(tol)3 has Keq = 2.0 +/- 0.5, follows second
      order kinetics with k = (1.1 +/- 0.2) x 105 M-1 s-1 (DeltaG = 11 kcal mol-1), and
      has a primary isotope effect kH/kD = 2.4 +/- 0.4. Oxidation of HOAr-NH2 with
      [N(C6H4Br)3]*+ is faster, with k congruent with 4 x 107 M-1 s-1. The isotope
      effect, thermochemical arguments, and the dependence of the rate on driving force
      (DeltaDeltaG/DeltaDeltaG degrees = 0.53) all indicate that electron transfer from
      HOAr-NH2 must occur concerted with intramolecular proton transfer from the phenol
      to the amine (proton-coupled electron transfer, PCET). The data rule out stepwise
      paths that involve initial electron transfer to form the phenol radical cation
      *+HOAr-NH2 or that involve initial proton transfer to give the zwitterion -OAr
      NH3+. The dependence of the electron-transfer rate constants on driving force can
      be fit with the adiabatic Marcus equation, yielding a large intrinsic barrier:
      lambda = 34 kcal mol-1 for reactions of HOAr-NH2 with NAr3*+.

PMID- 15469235
TI  - Triggering DNAzymes with light: a photoactive C8 thioether-linked adenosine.
AB  - Herein we report evidence for a light-inducible DNAzyme. In so doing, we also
      disclose the synthesis and photochemical properties of a novel nucleoside: 8-(2
      (4-imidazolyl)ethyl-1-thio)-2'-deoxyriboadenosine (d1). The light sensitivity of
      (d1) was evaluated via an examination of the photoinduced reactivation of DNAzyme
      8-17E from an inactive form that contained a single nucleotide (d1) modification.
      Restoration of DNAzyme activity results from a photoinduced reversion of (d1) to
      unmodified deoxyadenosine. Deuterium studies indicate that water is the source of
      hydrogen in the C8-H product and not the alkylthio group, suggesting that
      reversion of (1) to adenosine is not a consequence of simple homolysis of the C8
      S bond but of an unprecedented photochemical conversion. This adenosine, which
      affords significant control of catalytic reactivation of a DNAzyme, may find
      general use in photodecaging other biological systems.

PMID- 15469236
TI  - Direct electron transfer to the oxygenase domain of neuronal nitric oxide
      synthase (NOS): exploring unique redox properties of NOS enzymes.
AB  - Thin film direct electrochemistry shows that the oxygenase domain of neuronal
      nitric oxide synthase undergoes reversible electron transfer with an underlying
      electrode. The midpotential of the FeIII/FeII couple is found to be modulated by
      both the binding of the tetrahydropterin cofactor and the pH of the buffer
      medium.

PMID- 15469237
TI  - Stimuli-responsive supramolecular nanocapsules from amphiphilic calixarene
      assembly.
AB  - We synthesized tetrameric amphiphilic molecules based on a calixarene building
      block that self-assembles into a tunable and stable aggregation structure in
      aqueous solution. The amphiphilic calixarene molecules with a small hydrophilic
      part were observed to assemble into a vesicular structure that decreases
      significantly in diameter with only small increases in the hydrophilic chain
      length. Further increasing the chain length induced the collapse of the vesicles
      into spherical micelles. Remarkably, the vesicles were also observed to transform
      into small globular micelles at lower pH, which can be used to trigger the
      release of the encapsulated hydrophilic guest molecules.

PMID- 15469238
TI  - Electrostatic interactions dominate the catalytic contribution of arg39 in 4
      oxalocrotonate tautomerase.
AB  - The synthesis and kinetic parameters of a comprehensive set of 4-OT analogues
      with arginine (X = NH2+) to citrulline (X = O) substitutions at positions 11, 39,
      and 61 are reported. These data suggest that the main contribution of Arg39' ' to
      catalysis is by electrostatic stabilization of the anionic transition state
      leading to intermediate 2, and not by hydrogen bonding.

PMID- 15469239
TI  - Mechanically regulated rotation of a guest in a nanoscale host.
AB  - The spinning rate of an encapsulated cyclophane guest is affected by the "size"
      of the coguests.

PMID- 15469240
TI  - Plasmon mode imaging of single gold nanorods.
AB  - We have investigated two-photon-induced photoluminescence images and spectra of
      single gold nanorods by using an apertured scanning near-field optical
      microscope. The observed PL spectrum of single gold nanorod can be explained by
      the radiative recombination of the electron-hole pair near the X and L symmetry
      points. PL images reveal characteristic features reflecting an eigenfunction of a
      specific plasmon mode as well as electric field distributions around the nanorod.

PMID- 15469241
TI  - Shape-selective sensing of lipids in aqueous solution by a designed fluorescent
      molecular tube.
AB  - The design, synthesis, and recognition properties of two isomeric
      calixnaphthalene-type molecular tubes is described. The anti isomer showed strong
      fluorescence quenching upon titration with various simple lipid guests in water,
      in which the more hydrophobic guests associated with higher affinity. The syn
      isomer bound long straight-chain guests tightly with a similar fluorescence
      quenching response. However, the syn isomer was more selective, giving an
      increase in fluorescence upon titration of guests which could not thread through
      the tube. Thus, the syn isomer is a selective fluorescent sensor for long
      straight-chain lipids.

PMID- 15469242
TI  - Photochromic and luminescence switching properties of a versatile diarylethene
      containing 1,10-phenanthroline ligand and its rhenium(I) complex.
AB  - A versatile bis(2,5-dimethyl-3-thienyl)-1,10-phenanthroline photochromic ligand
      has been successfully synthesized via a Suzuki cross-coupling reaction. The
      excitation wavelength for photochromic reaction of the dithienylphenanthroline
      could be extended from lambda </= 340 nm in the UV region to ca. 480 nm in the
      visible region, corresponding to the MLCT excitation, through the incorporation
      into the rhenium(I) tricarbonyl system. Reversible switching of the emissive
      state by the photochromic reaction has also been demonstrated.

PMID- 15469243
TI  - Electrophoretic analysis and purification of fluorescent single-walled carbon
      nanotube fragments.
AB  - Arc-synthesized single-walled carbon nanotubes have been purified through
      preparative electrophoresis in agarose gel and glass bead matrixes. Two major
      impurities were isolated: fluorescent carbon and short tubular carbon. Analysis
      of these two classes of impurities was done. The methods described may be readily
      extended to the separation of other water-soluble nanoparticles. The separated
      fluorescent carbon and short tubule carbon species promise to be interesting
      nanomaterials in their own right.

PMID- 15469244
TI  - Coaxially gated in-wire thin-film transistors made by template assembly.
AB  - Nanowire field effect transistors were prepared by a wet chemical template
      replication method using anodic aluminum oxide membranes. The membrane pores were
      first lined with a thin SiO2 layer by the surface sol-gel method. Au, CdS (or
      CdSe), and Au wire segments were then sequentially electrodeposited within the
      pores, and the resulting nanowires were released by dissolution of the membrane.
      Electrofluidic alignment of these nanowires between source and drain leads and
      evaporation of gold over the central CdS (CdSe) stripe affords a "wrap-around
      gate" structure. At VDS = -2 V, the Au/CdS/Au devices had an ON/OFF current ratio
      of 103, a threshold voltage of 2.4 V, and a subthreshold slope of 2.2 V/decade. A
      3-fold decrease in the subthreshold slope relative to that of planar
      nanocrystalline CdSe devices can be attributed to coaxial gating. The control of
      dimensions afforded by template synthesis should make it possible to reduce the
      gate dielectric thickness, channel length, and diameter of the semiconductor
      segment to sublithographic dimensions while retaining the simplicity of the wet
      chemical synthetic method.

PMID- 15469245
TI  - A photopatternable pentacene precursor for use in organic thin-film transistors.
AB  - We demonstrate that modifying pentacene to incorporate an acid-labile moiety into
      its molecular structure leads to a new precursor that can be easily deposited,
      photopatterned, and processed via wet-chemical methods to produce organic
      semiconducting devices exhibiting good electrical characteristics. Acidic
      conditions produced by ultraviolet illumination of a co-deposited photoacid
      generator greatly accelerate the local conversion of this N-sulfinyl-tert
      butylcarbamate pentacene adduct back to pentacene. Photopatterned thin-film
      transistors exhibit carrier mobilities in excess of 0.1 cm2 V-1 s-1, making this
      an attractive precursor for fabrication of large-area organic electronics via
      solution-phase methods.

PMID- 15469246
TI  - An unusual zwitterionic, diradical intermediate in photochemical electron
      transfer substitution reactions.
AB  - An unusual zwitterionic diradical intermediate complex R*...X-...HR'B*+ is
      generated during the photoinduced electron-transfer substitution reaction between
      alkyl halides (RX) and Lewis bases (HR'B). This reaction intermediate was
      observed for the 1-chloroadamantane and tert-butylamine system in a hydrocarbon
      glass at 25 K by electron spin resonance spectroscopy. Ab initio density
      functional calculations were carried out to examine the physical and electronic
      structure of the intermediate.

PMID- 15469248
TI  - Sugar-based microemulsion glass templates.
AB  - Complex fluids comprising of surfactants with water and/or oil form a rich
      variety of dynamic self-assembled structures, ranging from spherical swollen
      micelles, viscous rod-like micelles, and bicontinuous microemulsions to ordered
      liquid crystalline phases. The wide range of practical and specialized
      applications of complex fluids has made them the subject of intense research for
      many decades. Here, we demonstrate for the first time how bicontinuous
      microemulsions containing equal masses of oil and sugar can be driven to the
      glassy state without phase separation at ambient temperatures by controlled
      desiccation of sugar-rich microemulsions. The robust nanostructure of these
      microemulsion glasses allows polymerization of hydrophobic liquid monomers within
      the interstices of the glassy microemulsion template without macroscopic phase
      separation. Yet after polymerization, the sugar and surfactant template can be
      easily removed by dissolution in water.

PMID- 15469247
TI  - Dendritic macromers as in situ polymerizing biomaterials for securing cataract
      incisions.
AB  - Dendritic macromers are attractive macromolecules for hydrogel formation since
      high cross-linking densities at low polymer concentration can be obtained, varied
      physical properties can be observed based on the macromer structure, and low
      viscous aqueous solutions can be injected in an in vivo site of irregular shaped
      to form a well-integrated polymer network. A peptide dendron possessing terminal
      cysteine residues was synthesized and characterized. When this peptide dendron
      was mixed with poly(ethylene glycol dialdehyde) in aqueous solution at pH = 7.4,
      a hydrogel spontaneously formed as a consequence of thiazolidine linkages between
      the macromers. Such in situ polymerized hydrogels are of interest for tissue
      engineering and wound-repair applications. To evaluate the potential use of this
      hydrogel sealant in ophthalmic surgeries, a 3-mm clear corneal incision (i.e.,
      the wounds created during a typical cataract surgery) was successfully sealed.

PMID- 15469249
TI  - Modified DNA analogues that sense light exposure with color changes.
AB  - We report the discovery of a new class of light-sensing molecules. These light
      sensors are composed of fluorophore oligomers assembled on a DNA backbone. A
      combinatorial library of tetrafluorophores consisting of over 14 000 compounds
      was synthesized and screened for rapid responses toward light exposure. Among the
      most light-sensitive molecules, at least three tetramers were found to respond to
      light exposure with apparent color changes, rather than simple photobleaching.

PMID- 15469250
TI  - Site-specific assembly of DNA and appended cargo on arrayed carbon nanotubes.
AB  - We describe a strategy that permits discrete regions of arrayed carbon nanotubes
      (CNTs) to be functionalized simultaneously and specifically with DNA
      oligonucleotides. The different chemical properties of two regions on single CNTs
      and orthogonal chemical coupling strategies have been exploited to derivatize
      CNTs within highly ordered arrays with multiple DNA sequences. Through duplex
      hybridization, we then targeted different DNA sequences with appended metal
      nanoparticles to distinct sites on the CNT architecture with precise spatial
      control. The materials generated from these studies represent the first CNTs with
      bipartite functionalization. The approach described provides a high level of
      precision in parallel and directed assembly of DNA sequences and appended cargo
      and is useful for the preparation of novel hybrid bionanomaterials.

PMID- 15469251
TI  - Amino acid backbone specificity of the Escherichia coli translation machinery.
AB  - Using a pure Escherichia coli translation system, we tested the intrinsic
      specificity of the protein biosynthetic machinery by determining the relative
      yields of peptide synthesis for incorporation of a series of acyl
      %@mt;sys@%tRNA%@sx@%GAC%@be@%AsnB%@sxx@%%@mx@% 's with varied backbone structures
      at the sense codon GUU (Val). The results showed that different amino acids on
      the same tRNA adaptor give significantly different peptide yields and the
      potential for cross-talk between the amino acid and tRNA body/anticodon in aa
      tRNA decoding by the ribosome. They further support the substrate plasticity of
      the ribosomal biosynthetic machinery and provide immediate candidates for
      ribosomally encoded polymer synthesis.

PMID- 15469252
TI  - Long-range 1H-19F distance measurement in peptides by solid-state NMR.
AB  - A new NMR technique for determining long-range 1H-19F distances in solids is
      demonstrated. Using a modified rotational-echo double resonance (REDOR) sequence
      involving 1H homonuclear decoupling and composite 19F pulses, we show that it is
      possible to determine 1H-19F distances to approximately 8 A. The detrimental
      effect of the large 19F chemical shift to REDOR dephasing is partially
      compensated for by the composite pulse, 90 degrees 225 degrees 315 degrees . The
      1HNLeu-19FPhe distance in the peptide f-MLF-OH was found to be 7.7 A. This was
      used to refine the Phe side chain conformation. The 1H-19F REDOR technique should
      be useful for restraining the three-dimensional structure of proteins.

PMID- 15469253
TI  - Semiconductor-encapsulated peptide-amphiphile nanofibers.
AB  - We report here on the use of peptide-amphiphile (PA) nanofibers displaying the
      S(P)RGD peptide sequence on their exterior as templates for the mineralization of
      cadmium sulfide (CdS). At low Cd:PA ratios, the nanofibers nucleate and organize
      quantum-confined 3-5 nm CdS nanocrystals into linear arrays. Tubular structures,
      in which the PA fibers are completely encapsulated by the semiconductor, are
      produced at higher Cd:PA ratios.

PMID- 15469254
TI  - The pseudouridine synthases: revisiting a mechanism that seemed settled.
AB  - RNA containing 5-fluorouridine, [f 5U]RNA, has been used as a mechanistic probe
      for the pseudouridine synthases, which convert uridine in RNA to its C-glycoside
      isomer, pseudouridine. Hydrated products of f 5U were attributed to ester
      hydrolysis of a covalent complex between an essential aspartic acid residue and f
      5U, and the results were construed as strong support for a mechanism involving
      Michael addition by the aspartic acid residue. Labeling studies with [18O]water
      are now reported that rule out such ester hydrolysis in one pseudouridine
      synthase, TruB. The aspartic acid residue does not become labeled, and the
      hydroxyl group in the hydrated product of f 5U derives directly from solvent. The
      hydrated product, therefore, cannot be construed to support Michael addition
      during the conversion of uridine to pseudouridine, but the results do not rule
      out such a mechanism. A hypothesis is offered for the seemingly disparate
      behavior of different pseudouridine synthases toward [f 5U]RNA.

PMID- 15469255
TI  - Rendering poly(amidoamine) or poly(propylenimine) dendrimers temperature
      sensitive.
AB  - The poly(amidoamine) dendrimers having terminal isobutyramide (IBAM) groups were
      prepared by the reaction of isobutyric acid and the amine-terminated
      poly(amidoamine) dendrimers with generations (G) of 2 to 5 by using a condensing
      agent, 1,3-dicyclohexylcarbodiimide. 1H and 13C NMR revealed that an IBAM group
      was attached to essentially every chain end of the dendrimers. While the IBAM
      terminated G2 dendrimer was soluble in water, the IBAM-terminated G3, G4, and G5
      dendrimers exhibited the lower critical solution temperatures (LCSTs) at 75, 61,
      and 43 degrees C, respectively. Because the density of the terminal IBAM groups
      in the periphery of the dendrimer progressively increases with increasing
      dendrimer generation, the interaction of the IBAM groups might take place more
      efficiently, resulting in a remarkable decrease in the LCST. In addition,
      attachment of IBAM groups to poly(propylenimine) dendrimers could give the
      temperature-sensitive property, indicating that this is an efficient method to
      render dendrimers temperature sensitive.

PMID- 15469256
TI  - Nonionic side chains modulate the affinity and specificity of binding between
      functionalized polyamines and structured RNA.
AB  - This Communication introduces side-chain-bearing polyamines as molecules for
      selective recognition of folded RNA structures. The complex folded structures
      associated with RNA create binding pockets for proteins, and also binding sites
      for small molecules. Developing organic molecules that can bind RNA with high
      affinity and specificity is a challenge that must be overcome for RNA to be
      considered a viable drug target. In this work, six polyamines with different side
      chains were synthesized to test for effects on binding affinity and specificity
      to TAR RNA and RRE RNA of HIV. Binding interactions between polyamines and RNAs
      were examined using two footprinting assays, based on terbium-induced cleavage
      and magnesium-catalyzed cleavage at higher pH. The binding constants and the
      binding specificity were highly dependent on the side chains of the polyamines,
      demonstrating that this class of molecules is a very promising starting point for
      development of highly selective RNA-binding ligands.

PMID- 15469257
TI  - Organolanthanide-catalyzed synthesis of phosphine-terminated polyethylenes.
AB  - Organolanthanide-mediated hydrophosphination and ethylene polymerization are
      coupled in a catalytic cycle to produce diphenylphosphine-terminated
      polyethylenes. The resulting polymers were characterized by 1H, 13C, and 31P NMR,
      GPC, and DSC and compared spectroscopically to the model compound, 1
      eicosyldiphenylphosphine oxide. High activities (107 g polymer/(mol Ln.atm
      ethylene.h)) and narrow polydispersities were observed in the
      polymerization/chain transfer process. Polyethylene molecular weights were found
      to be inversely proportional to diphenylphosphine concentration, supporting a
      chain transfer mechanism. The present discovery represents the first case in
      which an electron-rich phosphine functions efficiently as a chain transfer agent
      in a single-site fn/d0-mediated olefin polymerization process.

PMID- 15469258
TI  - Stepwise hydration and multibody deprotonation with steep negative temperature
      dependence in the benzene.+ -water system.
AB  - We studied the stepwise hydration and solvent-mediated deprotonation of the
      benzene*+ cation (Bz*+) and found several unusual features. The solvent binding
      energies DeltaH on-1,n for the reactions Bz*+(H2O)n-1 + H2O --> Bz*+(H2O)n are
      nearly constant at 9 +/- 1 kcal mol-1 for n = 1 to 8. We observed a remarkable
      sudden decrease in the entropy of association accompanying the formation of
      Bz*+(H2O)7 and Bz*+(H2O)8, indicating strong orientational restraint in the
      hydration shells of these clusters consistent with the formation of cagelike
      structures. We observed the size-dependent deprotonation of Bz*+ in a cooperative
      multibody process, where n H2O molecules (n >/= 4) can remove a proton from Bz*+
      to form protonated water clusters. We measured, for the first time, the
      temperature dependence of such a process and found a negative temperature
      coefficient of a magnitude unprecedented in any chemical reaction, of the form k
      = AT-67+/- 4, or in an Arrhenius form having an activation energy of -34 +/- 1
      kcal mol-1. The temperature effect may be explained by Bz*+ and four H2O
      molecules needing to be assembled from gas-phase components to form the reactive
      species. Such large temperature effects may be therefore general in solvent
      cluster-mediated reactions.

PMID- 15469259
TI  - Competitive 15N kinetic isotope effects of nitrogenase-catalyzed dinitrogen
      reduction.
AB  - Biological N2 fixation is achieved under ambient conditions by enzymatic
      catalysis. The enzyme nitrogenase has been studied extensively, but the N2
      chemical reduction step is, by far, not rate limiting and hard to examine. A new
      method was developed that allows studying the reduction transition state within
      the enzyme's complex kinetic cascade by means of the 15N kinetic isotope effect
      on the reaction's second-order rate constant, V/K. A value of 1.7% +/- 0.2% was
      measured.

PMID- 15469260
TI  - Triplet (pi,pi) reactivity of the guanine-cytosine DNA base pair: benign
      deactivation versus double tautomerization via intermolecular hydrogen transfer.
AB  - Ab initio computations (CASSCF/6-31G* supported by CAS-PT2 single-point
      calculations) are used to study the reactivity of the triplet excited state of
      the guanine-cytosine DNA base pair. When the triplet excitation is centered on
      cytosine there is a competition between benign deactivation to the ground state
      and a hydrogen transfer route that can trigger double tautomerization. The
      calculated barriers favor the benign deactivation, but this route goes through a
      singlet/triplet intersystem crossing with small spin-orbit coupling. Therefore,
      the potentially mutagenic, double tautomerization route cannot be ruled out
      completely, and the two paths are probably an alternative to the well-known
      cytidine photodimerization reaction.

PMID- 15469261
TI  - Perfluorocyclobutyl-linked hexa-peri-hexabenzocoronene networks.
AB  - Hexa-peri-hexabenzocoronene (HBC) derivatives possess many interesting properties
      ranging from liquid crystallinity, to hole transport, to variable emission
      behavior, yet are plagued by insolubility and general accessibility of
      polymerizable substituents. The first synthesis of trifluorovinyl ether
      substituted hexabenzocoronene and its polymerization to perfluorocyclobutyl
      (PFCB) polymers and copolymers is shown. Unlike hydrocarbon ethers, fluoro vinyl
      ethers are stable under HBC oxidation conditions. Discrete HBC units in PFCB
      polymers provide access to potentially processable HBC optical materials.

PMID- 15469262
TI  - An experimental strategy to evaluate the thermodynamic stability of highly
      dynamic binding sites in proteins using hydrogen exchange.
AB  - Quantitative characterization of the stability of highly dynamic regions in
      proteins is a significant goal because it represents a cornerstone to an
      understanding of the role of dynamics in function. Due to experimental
      constraints, however, monitoring the local stability of highly dynamic regions
      using standard hydrogen exchange (HX) methods is not a viable approach. Here, an
      experimental strategy is outlined that takes advantage of the coupling between
      stability as monitored by HX and binding affinity as monitored by isothermal
      titration calorimetry. It is shown that the stability of dynamic regions, which
      are part of binding sites, can be inferred from the response of the system to Gly
      mutations at surface-exposed sites. When applied to the analysis of the highly
      dynamic RT loop of SEM5 C-terminal SH3 domain, this approach reveals that the
      energetic consequences of the observed conformational heterogeneity are
      significant.

PMID- 15469263
TI  - Stereoselective synthesis of highly substituted Delta1-pyrrolines: exo-selective
      1,3-dipolar cycloaddition reactions with azlactones.
AB  - We report herein a silver(I)-catalyzed exo-selective synthesis of highly
      substituted Delta1-pyrroline scaffolds from amino acid-derived munchnones. Silver
      acetate successfully catalyzed the cycloaddition reaction of azlactones with
      alkenes, generating Delta1-pyrrolines in very good yields without isomerization
      to the Delta2-pyrrolines or decarboxylation.

PMID- 15469264
TI  - 14-electron disilene palladium complex having strong pi-complex character.
AB  - The first 14-electron disilene palladium complex eta2-[tetrakis(tert
      butyldimethylsilyl)disilene](tricyclohexylphosphine)palladium (4) was
      synthesized. In the solid state, complex 4 has one tricyclohexylphosphine ligand
      bound unsymmetrically to the palladium center in regard to the eta2-disilene
      moiety. The elongation of the Si-Si bond length from that of the corresponding
      free disilene (3.2%) and the bent back angles of the disilene moiety (4.41
      degrees and 9.65 degrees ) for 4 were much smaller than those for the
      corresponding 16-electron eta2-disilene complex (Me3P)2Pd[tetrakis(tert
      butyldimethylsilyl)disilene] (4.6% and 27.2 degrees , respectively). Complex 4 is
      regarded as the complex having the strongest pi-complex character among the known
      disilene complexes. Highly symmetric NMR spectra were observed for 4; central Si1
      and Si2 nuclei were equivalent and appeared as a doublet with 2J(29Si-31P) of 19
      Hz, indicating facile flipping of the phosphine ligand in the Pd-Si-Si plane.

PMID- 15469265
TI  - Efficient photocurrent generation by self-assembled monolayers composed of 3 10
      helical peptides carrying linearly spaced naphthyl groups at the side chains.
AB  - Self-assembled monolayers (SAMs) were prepared on a gold substrate from a 310
      helical peptide carrying three naphthyl groups at the side chain (SSN3B) or from
      the reference peptides carrying no or one naphthyl group. The 310-helical
      conformation of SSN3B in solution was confirmed by 1H NMR spectroscopy and
      geometry optimization. Cyclic voltammetry and infrared absorption-reflection
      spectroscopy showed vertical molecular orientation and a well-packed structure in
      the SSN3B SAM. Anodic photocurrent was successfully generated by the SSN3B SAM in
      the presence of triethanolamine, and the current intensity was found to be much
      larger than those by the other SAMs from peptides carrying one naphthyl group. It
      was therefore concluded that the linearly spaced naphthyl groups along the
      helical axis act as photosensitizer and electron-hopping site to promote
      photocurrent generation remarkably.

PMID- 15469266
TI  - Fluorinated carbon with ordered mesoporous structure.
AB  - Fluorination and structural change of highly ordered mesoporous carbons were
      studied. Mesoporous and fluorinated carbons with ordered cubic structure were
      synthesized and characterized with TEM, FTIR, adsorption, and EDX.

PMID- 15469267
TI  - Copper-catalyzed enantioselective conjugate addition of grignard reagents to
      acyclic enones.
AB  - A highly enantioselective Cu-catalyzed addition of Grignard reagents to acyclic
      aliphatic enones is described. In the presence of 5 mol % of CuBr.SMe2 and 6 mol
      % of JosiPhos diphosphine aliphatic enones react with Grignard reagents to
      provide beta-substituted linear ketones with high yields, regio-, and
      enantioselectivities.

PMID- 15469268
TI  - Influence of electron correlation effects on the solvation of Cu2+.
AB  - Hybrid QM/MM MD simulations including electron correlation effects at MP2 level
      were performed to obtain an accurate picture of the solvation structure and the
      Jahn-Teller effect of the Cu2+ ion.

PMID- 15469269
TI  - Resonance Raman spectroscopy of the neutral radical Trp306 in DNA photolyase.
AB  - The resonance Raman spectrum of the tryptophan neutral radical in a protein,
      Escherichia coli photolyase, is reported for the first time. The data compare
      very well to a solution study and computational predictions, and tentative
      assignments are made for the observed vibrations. This important new result
      demonstrates the potential of time-resolved resonance Raman spectroscopy as a
      powerful tool to investigate these radicals in protein electron-transfer
      processes and in enzymatic reactions in real time.

PMID- 15469270
TI  - Enantioselective total synthesis of (+)-gigantecin: exploiting the asymmetric
      glycolate aldol reaction.
AB  - The enantioselective synthesis of the potent, selective, cytotoxic, annonaceous
      acetogenin, (+)-gigantecin, has been completed. An asymmetric glycolate aldol
      serves to establish the stereocenters at C13,14 and at C21,22. A Carreira
      asymmetric acetylide addition is used to establish the C17 stereocenter.

PMID- 15469271
TI  - Ru3(CO)12-catalyzed silylation of benzylic C-H bonds in arylpyridines and
      arylpyrazoles with hydrosilanes via C-H bond cleavage.
AB  - Ruthenium-catalyzed silylation of sp3 C-H bonds at a benzylic position with
      hydrosilanes gave benzylsilanes. For this silylation reaction, Ru3(CO)12 complex
      showed high catalytic activity. This silylation proceeded at the methyl C-H bond
      selectively. For this silylation reaction, pyridyl and pyrazolyl groups, and the
      imino group in hydrazones, can function as a directing group. Several
      hydrosilanes involving triethyl-, dimethylphenyl-, tert-butyldimethyl-, and
      triphenylsilanes can be used as a silylating reagent. Coordination of an sp2
      nitrogen atom to the ruthenium complex is important for achieving this silylation
      reaction.

PMID- 15469272
TI  - DNA cleavage induced by thermal electron transfer from a dimeric NADH analogue to
      acridinium ions in the presence of oxygen.
AB  - Acridinium ions, which can intercalate to DNA, act as thermal DNA cleavers in the
      presence of a dimeric NADH analogue and O2 in an aqueous solution via thermal
      electron transfer from a dimeric NADH analogue to acridinium ions, followed by
      the electron-transfer reduction of O2 to O2*- by the resulting NAD radicals.

PMID- 15469273
TI  - Arylene ethynylene macrocycles prepared by precipitation-driven alkyne
      metathesis.
AB  - A convenient, multigram-scale synthesis of arylene ethynylene macrocycles near
      room temperature is described. Driven by the precipitation of a diarylacetylene
      byproduct, alkyne metathesis produces the desired macrocycles in one step from
      monomers in high yields.

PMID- 15469274
TI  - Structures and dynamics of self-assembled surface monolayers observed by
      ultrafast electron crystallography.
AB  - In this communication, we report our first study of self-assembled adsorbates on
      metal surfaces. Specifically, we studied single-crystal clean surfaces of Au(111)
      with and without a monolayer of reaction involving the assembly of 2
      mercaptoacetic acid from 2,2'-dithiodiacetic acid. We also studied monolayers of
      iron hemes. With ultrafast electron crystallography, we are able to observe and
      isolate structural dynamics of the substrate (gold) and adsorbate(s) following an
      ultrafast temperature jump.

PMID- 15469275
TI  - Characterization of nonspecific protein-DNA interactions by 1H paramagnetic
      relaxation enhancement.
AB  - Nonspecific protein-DNA interactions play an important role in a variety of
      contexts related to DNA packaging, nucleoprotein complex formation, and gene
      regulation. Biophysical characterization of nonspecific protein-DNA interactions
      at the atomic level poses significant challenges owing to the dynamic nature of
      such complexes. Although NMR spectroscopy represents a powerful tool for the
      analysis of dynamic systems, conventional NMR techniques have provided little
      information on nonspecific protein-DNA interactions. We show that intermolecular
      (1)H paramagnetic relaxation enhancement (PRE) arising from Mn(2+) chelated to an
      EDTA-group covalently attached to a thymine base (dT-EDTA-Mn(2+)) in DNA provides
      a unique approach for probing the global dynamics and equilibrium distribution of
      nonspecific protein-DNA interactions. For nonspecific DNA binding, similar
      intermolecular (1)H-PRE profiles are observed on the (1)H resonances of the bound
      protein when dT-EDTA-Mn(2+) is located at either end of a DNA oligonucleotide
      duplex. We demonstrate the applicability of this approach to HMG-box proteins and
      contrast the results obtained for nonspecific DNA binding of the A-box of HMGB-1
      (HMGB-1A) with sequence-specific DNA binding of the related SRY protein.
      Intermolecular (1)H-PRE data demonstrate unambiguously that HMGB-1A binds to
      multiple sites in multiple orientations even on a DNA fragment as short as 14
      base pairs. Combining the (1)H-PRE data with the crystal structure of the HMGB-1
      A-box/cisplatin-modified DNA complex allows one to obtain a semiquantitative
      estimate of the equilibrium populations at the various sites.

PMID- 15469276
TI  - In situ click chemistry: enzyme inhibitors made to their own specifications.
AB  - The in situ click chemistry approach to lead discovery employs the biological
      target itself for assembling inhibitors from complementary building block
      reagents via irreversible connection chemistry. The present publication discusses
      the optimization of this target-guided strategy using acetylcholinesterase (AChE)
      as a test system. The application of liquid chromatography with mass
      spectroscopic detection in the selected ion mode for product identification
      greatly enhanced the sensitivity and reliability of this method. It enabled the
      testing of multicomponent mixtures, which may dramatically increase the in situ
      screening throughput. In addition to the previously reported in situ product syn
      TZ2PA6, we discovered three new inhibitors, syn-TZ2PA5, syn-TA2PZ6, and syn
      TA2PZ5, derived from tacrine and phenylphenanthridinium azides and acetylenes, in
      the reactions with Electrophorus electricus and mouse AChE. All in situ-generated
      compounds were extremely potent AChE inhibitors, because of the presence of
      multiple sites of interaction, which include the newly formed triazole nexus as a
      significant pharmacophore.

PMID- 15469277
TI  - Photochemically induced dynamic nuclear polarization in photosystem I of plants
      observed by 13C magic-angle spinning NMR.
AB  - Photochemically induced dynamic nuclear polarization (photo-CIDNP) has been
      observed in photosystem I of spinach by (13)C magic angle spinning solid-state
      NMR under continuous illumination with white light. An almost complete set of
      chemical shifts of the aromatic ring carbons of a single Chl a molecule has been
      obtained which is assigned to the P2-cofactor of the primary electron donor P700.
      Since all light-induced (13)C NMR signals appear to be emissive, a predominance
      of the three-spin mixing mechanism over the differential decay mechanism is
      proposed. The origin of the strong contribution of the three-spin mixing
      mechanism and the differences with photosystem II are discussed.

PMID- 15469278
TI  - Systematic investigation of Saccharomyces cerevisiae enzymes catalyzing carbonyl
      reductions.
AB  - Eighteen key reductases from baker's yeast (Saccharomyces cerevisiae) have been
      overproduced in Escherichia coli as glutathione S-transferase fusion proteins. A
      representative set of alpha- and beta-keto esters was tested as substrates (11
      total) for each purified fusion protein. The stereoselectivities of beta-keto
      ester reductions depended both on the identity of the enzyme and the substrate
      structure, and some reductases yielded both L- and D-alcohols with high
      stereoselectivities. While alpha-keto esters were generally reduced with lower
      enantioselectivities, it was possible in all but one case to identify pairs of
      yeast reductases that delivered both alcohol antipodes in optically pure form.
      Taken together, the results demonstrate not only that individual yeast reductases
      can be used to supply important chiral building blocks, but that GST-fusion
      proteins allow rapid identification of synthetically useful biocatalysts (along
      with their corresponding genes).

PMID- 15469279
TI  - Catalytic unfolding and proteolysis of cytochrome C induced by synthetic binding
      agents.
AB  - A class of polyanionic copper porphyrin dimers is shown to selectively increase
      the susceptibility of cytochrome c to proteolysis through binding-induced
      disruption of tertiary and secondary structure. The free energy of the protein
      conformation leading to proteolytic attack is stabilized by about 2.4 kcal/mol in
      the bound state. The proteolytic acceleration is catalytic in nature, requiring
      only a fraction of an equivalent of metalloporphyrin to effect complete, rapid
      digestion in the presence of a protease.

PMID- 15469280
TI  - Lifetime regulation of the charge-separated state in DNA by modulating the
      oxidation potential of guanine in DNA through hydrogen bonding.
AB  - A series of naphthalimide (NI)- and 5-bromocytosine ((br)C)-modified
      oligodeoxynucleotides (ODNs) were prepared, and their lifetimes of the charge
      separated states during the photosensitized one-electron oxidation of DNA were
      measured. Various lifetimes of the charge-separated states were observed
      depending on the sequence and the incorporation sites of (br)C, and the oxidation
      potential of G in the (br)C:G base-pair relative to that of G in the C:G base
      pair and in the GGG sequence was determined by comparing the lifetimes of the
      charge-separated states. The change in the cytosine C5 hydrogen to bromine
      resulted in a 24 mV increase in the oxidation potential of G in the (br)C:G base
      pair as compared to that of G in the C:G base-pair, the value of which is
      comparable to a 58 mV decrease in the oxidation potential of G in the GGG
      sequence. These results clearly demonstrate that hole transfer in DNA can be
      controlled through hydrogen bonding by introducing a substituent on the cytosine.

PMID- 15469281
TI  - IspH protein of Escherichia coli: studies on iron-sulfur cluster implementation
      and catalysis.
AB  - The ispH gene of Escherichia coli specifies an enzyme catalyzing the conversion
      of 1-hydroxy-2-methyl-2-(E)-butenyl diphosphate into a mixture of isopentenyl
      diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) in the nonmevalonate
      isoprenoid biosynthesis pathway. The implementation of a gene cassette directing
      the overexpression of the isc operon involved in the assembly of iron-sulfur
      clusters into an Escherichia coli strain engineered for ispH gene expression
      increased the catalytic activity of IspH protein anaerobically purified from this
      strain by a factor of at least 200. For maximum catalytic activity, flavodoxin
      and flavodoxin reductase were required in molar concentrations of 40 and 12
      microM, respectively. EPR experiments as well as optical absorbance indicate the
      presence of a [3Fe-4S](+) cluster in IspH protein. Among 4 cysteines in total,
      the 36 kDa protein carries 3 absolutely conserved cysteine residues at the amino
      acid positions 12, 96, and 197. Replacement of any of the conserved cysteine
      residues reduced the catalytic activity by a factor of more than 70 000.

PMID- 15469282
TI  - Analysis on a cooperative pathway involving multiple cations in hammerhead
      reactions.
AB  - The hammerhead ribozyme reaction is more complex than might have been expected,
      perhaps because of the flexibility of RNA, which would have enhanced the
      potential of RNA during evolution of and in the RNA world. Divalent Mg(2+) ions
      can increase the rate of the ribozyme-catalyzed reaction by approximately 10(9)
      fold as compared to the background rate under standard conditions. However, the
      role of Mg(2+) ions is controversial since the reaction can proceed in the
      presence of high concentrations of monovalent ions, such as Li(+), Na(+), and
      NH(4)(+) ions, in the absence of divalent ions. We thus carried out ribozyme
      reactions under various conditions, and we obtained parameters that explain the
      experimental data. On the basis of the analysis, we propose a new pathway in the
      hammerhead ribozyme reaction in which divalent metal ions and monovalent ions act
      cooperatively.

PMID- 15469283
TI  - Oxidation of carboxylic acids by horseradish peroxidase results in prosthetic
      heme modification and inactivation.
AB  - Hemoproteins are powerful oxidative catalysts. However, despite the diversity of
      functions known to be susceptible to oxidation by these catalysts, it is not
      known whether they can oxidize carboxylic acids to carboxylic radicals. We report
      here that incubation of horseradish peroxidase (HRP) at acidic pH with H(2)O(2)
      in acetate buffer results in rapid modification of the heme group and loss of
      catalytic activity. Mass spectrometry and NMR indicate that an acetoxy group is
      covalently bound to the delta-meso-carbon in the modified heme. A heme with a
      hydroxyl group on the 8-methyl is also formed as a minor product. These reactions
      do not occur if protein-free heme and H(2)O(2) are co-incubated in acetate
      buffer, if the HRP reaction is carried out at pH 7, in the absence of H(2)O(2),
      or if citrate rather than acetate buffer is used. A similar heme modification is
      observed in incubations with n-caproic and phenylacetic acids. A mechanism
      involving oxidation of the carboxyl group to a carboxylic radical followed by
      addition to the delta-meso-position is proposed. This demonstration of the
      oxidation of a carboxylic acid solidifies the proposal that a carboxylic radical
      mediates the normal covalent attachment of the heme to the protein in the
      mammalian peroxidases and CYP4 family of P450 enzymes. The hemoprotein-mediated
      oxidation of carboxylic acids, ubiquitous natural constituents, may play other
      roles in biology.

PMID- 15469284
TI  - Induced axial chirality in the biphenyl core of the Calpha-tetrasubstituted alpha
      amino acid residue Bip and subsequent propagation of chirality in (Bip)n/Val
      oligopeptides.
AB  - In the dipeptides Boc-Bip-L-Val-OMe and Boc-Bip-D-Val-OMe, an induced axial
      chirality in the biphenyl core of the Bip residue, a conformationally labile,
      proatropoisomeric C(alpha,alpha)-disubstituted glycine, was observed by
      electronic CD and (1)H NMR. Chiral induction is significantly higher when the Val
      residue is located at the C-terminal position of Bip. An outstanding phenomenon
      of propagation of chirality was demonstrated to occur in the related 3(10)
      helical -(Bip)n-L-Val (n = 2-6) oligopeptides by CD and vibrational CD
      techniques.

PMID- 15469285
TI  - Chemistry of the diazeniumdiolates. O- versus N-alkylation of the RNH[N(O)NO](-)
      ion.
AB  - Monomethylation of the potentially ambident RNH[N(O)NO](-) ion (R = isopropyl or
      cyclohexyl) has been shown to occur at the terminal oxygen to yield the novel
      diazeniumdiolate structural unit, RNHN(O)=NOMe. The NH bond of the product proved
      acidic, with a pK(a) of 12.3 in aqueous solution. The ultraviolet spectrum showed
      a large bathochromic shift on ionization (lambda(max) 244 --> 284 nm,
      epsilon(max) 6.9 --> 9.8 mM(-1) cm(-1)). Deprotonation led to a pH-dependent line
      broadening in the (1)H NMR spectrum of iPrNHN(O)=NOMe, suggesting a complex
      fluxionality possibly involving isomerizations around the N-N bonds. Consistent
      with this interpretation, evidence for extensive delocalization and associated
      changes in bond order on ionizing RNHN(O)=NOR' were found in density functional
      theory calculations using Gaussian 03 with B3LYP/6-311++G basis sets. With
      MeNHN(O)=NOMe as a model, all N-N and N-O bonds lengthened by 0.04-0.07 A as a
      result of ionization except for the MeN-N linkage, which shortened by 7%. These
      anions can be N-alkylated to generate R(1)R(2)NN(O)=NOR(3) derivatives that would
      otherwise be difficult to access synthetically. Additionally, some RNHN(O)=NOR'
      species may display unique and beneficial pharmacological properties. As one
      example, an agent with R = isopropyl and R' = beta-D-glucosyl was prepared and
      shown to generate nitric oxide in the presence of glucosidase at pH 5.

PMID- 15469286
TI  - Chemistry and biology of diazonamide A: first total synthesis and confirmation of
      the true structure.
AB  - With the addition of a tenth ring, the exchange of an oxygen atom for a nitrogen
      in the heart of the molecule, and a different terminal residue, the revised
      architecture for diazonamide A (1) provided an even more challenging molecular
      puzzle for chemical synthesis than its predecessor. In this article, we detail
      the first successful total synthesis of diazonamide A, an endeavor which not only
      verified its proper connectivities and established the stereochemistry of its
      previously unassignable C-37 chiral center, but which also was attended by the
      development of several new synthetic strategies and tactics.

PMID- 15469287
TI  - Chemistry and biology of diazonamide A: second total synthesis and biological
      investigations.
AB  - As an especially unique target for chemical synthesis, diazonamide A has the
      potential to be constructed through a plethora of synthetic routes, each attended
      by different challenges and opportunities for discovery. In this article, we
      detail our second total synthesis of diazonamide A through a sequence entirely
      distinct from that employed in our first campaign, one whose success required the
      development of several special strategies and tactics. We also disclose our
      complete studies regarding the chemical biology of diazonamide A and its
      structural congeners, and more fully delineate the scope of our protocol for
      Robinson-Gabriel cyclodehydration using pyridine-buffered POCl(3).

PMID- 15469288
TI  - Dendrimer interior functional group conversion and dendrimer metamorphosis--new
      approaches to the synthesis of oligo(dibenzyl sulfone) and
      oligo(phenylenevinylene) dendrimers.
AB  - A series of [G1] to [G3]-oligo(dibenzylsulfide) dendrimers containing up to 21
      interior dibenzylsulfide moieties was prepared as starting materials toward the
      syntheses of two new series of oligo(dibenzyl sulfone) and
      oligo(phenylenevinylene) dendrimers using two different dendrimer-to-dendrimer
      conversion strategies. The first strategy entailed the interior functionalization
      of the [G1] to [G3]-oligo(dibenzylsulfide)s to the corresponding [G1] to [G3]
      oligo(dibenzyl sulfone)s via hydrogen peroxide oxidation. Successful conversions
      of up to 21 interior dibenzylsulfide moieties to the corresponding dibenzyl
      sulfone groups were demonstrated. The second involved the skeletal
      rearrangements, also named as dendrimer metamorphosis, of the [G1] and [G2]
      oligo(dibenzyl sulfone) dendritic backbones to the corresponding [G1] and [G2]
      oligo(phenylenevinylene)s dendrimers via the Ramberg-Backlund (RB) reaction. Up
      to nine RB rearrangements on a dendrimer skeleton were realized and the
      conversion efficiency of each single RB rearrangement reaction was found to be
      96%.

PMID- 15469289
TI  - Aromatic gold and silver "rings": hydrosilver(I) and hydrogold(I) analogues of
      aromatic hydrocarbons.
AB  - Quantum chemical calculations suggest that a series of molecules with the general
      formula cyclo-Mn(mu-H)n (M = Ag, Au; n = 3-6) are stable. All cyclo-MnHn species,
      except cyclo-Au(3)H(3), have the same symmetry with the respective aromatic
      hydrocarbons but differ in that the hydrogen atoms are in bridging positions
      between the metal atoms and not in terminal positions. The aromaticity of the
      hydrosilver(I) and hydrogold(I) analogues of aromatic hydrocarbons was verified
      by a number of established criteria of aromaticity, such as structural,
      energetic, magnetic, and chemical criteria. In particular, the nucleus
      independent chemical shift, the relative hardness, Deltaeta, the electrophilicity
      index, omega, and the chemical reactivity toward electrophiles are indicative for
      the aromaticity of the hydrosilvers(I) and hydrogolds(I). A comprehensive study
      of the structural, energetic, spectroscopic (IR, NMR, electronic, and
      photoelectron spectra), and bonding properties of the novel classes of inorganic
      compounds containing bonds that are characterized by a common ring-shaped
      electron density, more commonly seen in organic molecules, is presented.

PMID- 15469290
TI  - Liquid crystalline bolaamphiphiles with semiperfluorinated lateral chains:
      competition between layerlike and honeycomb-like organization.
AB  - Novel bolaamphiphilic triblockmolecules consisting of a rigid biphenyl unit, with
      a polar 2,3-dihydroxypropyloxy group and a phenolic OH group at opposite ends, as
      well as a semiperfluorinated chain in a lateral position have been synthesized
      via palladium catalyzed cross coupling reactions as the key steps. The
      thermotropic liquid crystalline behavior of these compounds was investigated by
      polarized light microscopy, DSC and X-ray scattering, and the influence of the
      length of the lateral chain on the mesomorphic properties was studied. The
      compound with the shortest chain as well as the long chain derivatives form
      lamellar mesophases composed of segregated layers of the bolaamphiphilic moieties
      and sublayers comprising the fluid lateral chains. The layers within the lamellar
      phases of the short chain compound adopt a positional correlation, leading to a
      2D lattice (Col(r)/p2mm), whereas the layers of the lamellar phases of the long
      chain derivatives are noncorrelated (Lam). Compounds with a medium chain length
      organize into columnar phases, where the nonpolar lateral chains segregate into
      columns, which are embedded in networks of regular (Col(h)) or stretched
      (Col(r)/c2mm) hexagonal cylinder shells consisting of the bolaamphiphilic units.
      In total, an unusual phase sequence was found, where, with respect to the chain
      length, columnar mesophases occur between two mesophases with layer organization.

PMID- 15469291
TI  - L-shaped three-center two-electron (C-C-C)+ bonding array.
AB  - The structures and reactivities of the complexes between carbenium ions (R(+))
      and acetylene or propyne have been investigated with the aid of electron
      correlated quantum mechanical calculations (hybrid density functional,
      perturbation theory, and coupled cluster methods). Depending on the R group, the
      acetylene/carbenium ion interaction can produce either an "open" 3c-2e structure
      or the conventional vinyl cation structure. The "open" 3c-2e C-C-C bonding
      geometry exists as a minimum for R = methyl and primary/secondary/tertiary alkyl,
      and hence is the most notable. The alignment of three carbon centers is neither
      bridged nor linear, but L-shaped, and represents a new type of "open" 3c-2e
      bonding that has so far escaped proper attention.

PMID- 15469292
TI  - Synthesis and characterization of dendrimer templated supported bimetallic Pt-Au
      nanoparticles.
AB  - Bimetallic dendrimer-stabilized nanoparticles (DSNs) were used to prepare
      supported Pt-Au catalysts within the bulk miscibility gap for this binary system.
      Hydroxy-terminated generation 5 PAMAM dendrimers were used to prepare Cu(0)
      nanoparticles (NPs). The Cu(0) NPs were subsequently used to reduce K(2)PtCl(4)
      and HAuCl(4), preparing stabilized bimetallic Pt-Au NPs with a 1:1 stoichiometry.
      The stabilized NPs were adsorbed onto a high surface area silica support and
      thermally activated to remove the dendrimers. Transmission electron microscopy
      (TEM), energy dispersive spectroscopy (EDS), and infrared spectroscopy of
      adsorbed CO showed that this preparation route resulted in NPs in which the two
      metals are intimately mixed and that the majority of the bimetallic NPs were
      smaller than 3 nm. Further, the bimetallic NPs were highly active for CO
      oxidation catalysis near room temperature and showed evidence of CO induced
      restructuring at ambient temperatures.

PMID- 15469293
TI  - Gas-phase reactivity of charged pi-type biradicals.
AB  - Four pi,pi-biradicals, 2,6-dimethylenepyridinium and the novel isomers N-(3
      methylenephenyl)-3-methylenepyridinium, N-phenyl-3,5-dimethylenepyridinium, and N
      (3,5-dimethylenephenyl)pyridinium ions, were generated and structurally
      characterized in a Fourier transform ion cyclotron resonance mass spectrometer.
      Their gas-phase reactivity toward various reagents was compared to that of the
      corresponding monoradicals, 2-methylenepyridinium, N-phenyl-3
      methylenepyridinium, and N-(3-methylenephenyl)pyridinium ions. The biradicals
      reactivity was found to reflect their predicted multiplicity. The 2,6
      dimethylenepyridinium ion, the only biradical in this study predicted to have a
      closed-shell singlet ground state, reacts significantly faster than the other
      biradicals, which are predicted to have triplet ground states. In fact, this
      biradical reacts at a higher rate than the analogous monoradical, which suggests
      that to avoid the costly uncoupling of its unpaired electrons, the biradical
      favors ionic mechanisms over barriered radical pathways. In contrast, the second
      order reaction rate constants of the isomeric biradicals with triplet ground
      states are well approximated by those of the analogous monoradicals, although the
      final reaction products are sometimes different. This difference arises from
      rapid radical-radical recombination of the initial monoradical reaction products.
      The overall reactivity toward the hydrogen-atom donors benzeneselenol and
      tributylgermanium hydride is significantly greater for the radicals with the
      charged site in the same ring system as the radical site. This finding indicates
      that polar effects play an important role in controlling the reactivity of pi,pi
      biradicals, just as has been demonstrated for sigma,sigma-biradicals.

PMID- 15469294
TI  - Ab initio calculation of optical rotatory dispersion (ORD) curves: a simple and
      reliable approach to the assignment of the molecular absolute configuration.
AB  - In this paper, both Hartree-Fock (HF) and density functional theory (DFT) methods
      have been used to make ab initio calculations of the optical rotatory power of
      selected molecules at several wavelengths; that is, part of the optical rotatory
      dispersion (ORD) curve has been predicted. This approach constitutes a new,
      simple, and reliable method to assign the molecular absolute configuration, at
      least for rigid molecules such as those studied in the present work. In fact, in
      this way, it is possible to overcome the difficulties connected to some relevant
      cases, in particular that of (-)-beta-pinene, for which even a very high-level
      (DFT/B3LYP/6-311++G(2d,2p)) calculation affords the wrong sign of the optical
      rotation at 633 nm. On the contrary, the predicted ORD curve, even using small
      basis sets, reproduces (below 400 nm) the experimental trend well, allowing for
      the correct configurational assignment. This result clearly shows that to have a
      reliable configurational assignment the comparison between experimental and
      predicted rotation values must be carried out at different wavelengths and not at
      a single frequency. The reason for this is that working at wavelengths
      approaching the absorption maximum the [alpha](lambda) values become larger and
      their prediction becomes more reliable. Coupling the use of an inexpensive
      instrument (a polarimeter working at a few wavelengths) with the use of a DFT
      calculation package can also allow the experimental organic chemist to arrive,
      quickly and reliably, at the assignment of the molecular absolute configuration.

PMID- 15469295
TI  - Leaving group effects in gas-phase substitutions and eliminations.
AB  - Using a methodology recently developed for studying the product distributions of
      gas-phase S(N)2 and E2 reactions, the effect of the leaving group on the reaction
      rate and branching ratio was investigated. Using a dianion as the nucleophile,
      reactions with a series of alkyl bromides, iodides, and trifluoroacetates were
      examined. The alkyl groups in the study are ethyl, n-propyl, n-butyl, isobutyl,
      isopropyl, sec-butyl, and tert-butyl. The data indicate that leaving group
      abilities are directly related to the exothermicities of the reaction processes
      in both the gas phase and the condensed phase. Gas-phase data give a reactivity
      order of iodide > trifluoroacetate > bromide for S(N)2 and E2 reactions. Previous
      condensed phase data indicate a reactivity order of iodide > bromide >
      trifluoroacetate for substitution reactions; however, the basicities of bromide
      and trifluoroacetate are reversed in the condensed phase so this reactivity
      pattern does reflect the relative reaction exothermicities. Aside from this
      variation, the gas-phase data parallel condensed phase data indicating that the
      substituent effects are rooted in the nature of the alkyl substrate rather than
      in differences in solvation. The experimental data are supported by calculations
      at the MP2/6-311+G(d,p)//MP2/6-31+(d) level.

PMID- 15469296
TI  - CdSe and CdSe/CdS nanorod solids.
AB  - We demonstrate the self-organization of CdSe nanorods into nematic, smectic, and
      crystalline solids. Layered colloidal crystals of CdSe nanorods grow by slow
      destabilization of a nanocrystal solution upon allowing the diffusion of a
      nonsolvent into the colloidal solution of nanocrystals. The colloidal crystals of
      nanorods show characteristic birefringence, which we assign to specific
      spherulite-like texture of each nanorod assembly. To demonstrate the general
      character of nanorod self-assembly technique, CdSe/CdS heterostructure nanorods
      were organized into highly luminescent superlattices.

PMID- 15469297
TI  - Rhenium-based molecular rectangles as frameworks for ligand-centered mixed
      valency and optical electron transfer.
AB  - A series of six neutral, tetrametallic, molecular rectangles has been synthesized
      that have the form ([Re(CO)(3)](2)BiBzIm)(2)-mu,mu'-(LL)(2), where BiBzIm is 2,2'
      bisbenzimidazolate and LL is a reducible, dipyridyl or diazine ligand. X-ray
      crystallographic studies of the six show that the rectangle frameworks, as
      defined by the metal atoms, range in size from 5.7 A x 7.2 A to 5.7 A x 19.8 A.
      The singly reduced rectangles are members of an unusual category of mixed-valence
      compounds in which the ligands themselves are the redox centers and interligand
      electronic communication is controlled by direct ligand orbital overlap rather
      than by superexchange through the metal ions. Despite nominally identical
      coordination-defined ligand positioning, the spectrally determined electronic
      strengths, H(ab)2, vary by roughly 100-fold. As shown by X-ray crystallography
      and computational modeling, the observed differences largely reflect detailed
      geometric configurational differences that can either facilitate or frustrate
      productive direct orbital overlap.

PMID- 15469298
TI  - Mechanistic evidence for an alpha-oxoketene pathway in the formation of beta
      ketoamides/esters via Meldrum's acid adducts.
AB  - A practical, one-pot process for the preparation of beta-keto amides via a three
      component reaction, including Meldrum's acid, an amine, and a carboxylic acid,
      has been developed. Key to development of an efficient, high-yielding process was
      an in-depth understanding of the mechanism of the multistep process. Kinetic
      studies were carried out via online IR monitoring and subsequent principal
      component analysis which provided a means of profiling the concentration of both
      the anionic and free acid forms of the Meldrum's adduct 6 in real time. These
      studies, both in the presence and absence of nucleophiles, strongly suggest that
      formation of beta-keto amides from acyl Meldrum's acids occurs via alpha
      oxoketene species 2 and rule out other possible reaction pathways proposed in the
      literature, such as via protonated alpha-oxoketene intermediates 3 or
      nucleophilic addition-elimination pathways.

PMID- 15469299
TI  - Heats of adsorption of linear CO species adsorbed on the Au degrees and Ti+delta
      sites of a 1% Au/TiO2 catalyst using in situ FTIR spectroscopy under adsorption
      equilibrium.
AB  - The heats of adsorption of two linear CO species adsorbed on the Au degrees
      particles (denoted L(Au degrees)) and on the Ti(+delta) sites (denoted
      L(Ti+delta)) of a 1% Au/TiO(2) catalyst are determined as the function of their
      respective coverage by using the AEIR procedure (adsorption equilibrium infrared
      spectroscopy) previously developed. Mainly, the evolutions of the IR band area of
      each adsorbed species (2184 cm(-1) for L(Ti+delta) and at 2110 cm(-1) for L(Au
      degrees)) as a function of the adsorption temperature T(a), at a constant CO
      adsorption pressure P(CO), provide the evolutions of the coverages
      theta(LTi+delta) and theta(LAu degrees ) of each adsorbed CO species with T(a) in
      isobar conditions that give the individual heats of adsorption. It is shown that
      they linearly vary from 74 to 47 kJ/mol for L(Au degrees ) and from 50 to 40
      kJ/mol for L(Ti+delta) at coverages 0 and 1, respectively. These values are
      consistent with literature data on model Au particles and TiO(2). In particular,
      it is shown that the mathematical formalism supporting the AEIR procedure can be
      applied to literature data on Au-containing solids (single crystals and model
      particles).

PMID- 15469300
TI  - Distinct electronic effects on reductive eliminations of symmetrical and
      unsymmetrical bis-aryl platinum complexes.
AB  - Symmetrical bis-aryl platinum complexes (DPPF)Pt(C(6)H(4)-4-R)(2) (R = NMe(2),
      OMe, CH(3), H, Cl, CF(3)) and electronically unsymmetrical bis-aryl platinum
      complexes (DPPF)Pt(C(6)H(4)-4-R)(C(6)H(4)-4-X) (R = CH(3), X = NMe(2), OMe, H,
      Cl, F, CF(3); R = OMe, X = NMe(2), H, Cl, F, CF(3); R = CF(3), X = H, Cl, NMe(2);
      and R = NMe(2), X = H, Cl) were prepared, and the rates of reductive elimination
      of these complexes in the presence of excess PPh(3) are reported. The platinum
      complexes reductively eliminated biaryl compounds in quantitative yields with
      first-order rate constants that were independent of the concentration of PPh(3).
      Plots of Log(k(obs)/k(obs(H))) vs Hammett substituent constants (sigma) of the
      para substituents R and X showed that the rates of reductive elimination
      reactions depended on two different electronic properties. The reductive
      elimination from symmetrical bis-aryl platinum complexes occurred faster from
      complexes with more electron-donating para substituents R. However, reductive
      elimination from a series of electronically unsymmetrical bis-aryl complexes was
      not faster from complexes with the more electron-donating substituents. Instead,
      reductive elimination was faster from complexes with a larger difference in the
      electronic properties of the substituents on the two platinum-bound aryl groups.
      The two electronic effects can complement or cancel each other. Thus, this
      combination of electronic effects gives rise to complex, but now more
      interpretable, free energy relationships for reductive elimination.

PMID- 15469301
TI  - An extremely active catalyst for the Negishi cross-coupling reaction.
AB  - A new catalyst system for the Pd-catalyzed cross-coupling of organozinc reagents
      with aryl halides (Negishi coupling) has been developed. This system permits
      efficient preparation of hindered biaryls (tri- and tetra-ortho-substituted),
      functions effectively at low levels of catalyst, and tolerates a wide range of
      functional groups and heterocyclic substrates. A systematic study of ligand
      structure was performed and was correlated with catalyst activity.

PMID- 15469302
TI  - Stoichiometric and catalytic H/D incorporation by cationic iridium complexes: a
      common monohydrido-iridium intermediate.
AB  - A mechanistic study of the stoichiometric and catalytic H/D exchange reactions
      involving cationic iridium complexes is presented. Strong evidence suggests that
      both stoichiometric and catalytic reactions proceed via a monohydrido-iridium
      species. Stoichiometric deuterium incorporation reactions introduce multiple
      deuterium atoms into the organic products when aryliridium compounds
      CpPMe(3)Ir(C(6)H(4)X)(OTf) (X = H, o-CH(3), m-CH(3), p-CH(3)) react with D(2).
      Multiple deuteration occurs at the unhindered positions (para and meta) of
      toluene, when X = CH(3). The multiple-deuteration pathway is suppressed in the
      presence of an excess of the coordinating ligand, CH(3)CN. The compound
      CpPMe(3)IrH(OTf) (1-OTf) is observed in low-temperature, stoichiometric
      experiments to support a monohydrido-iridium intermediate that is responsible for
      catalyzing multiple deuteration in the stoichiometric system. When paired with
      acetone-d(6)(), [CpPMe(3)IrH(3)][OTf] (4) catalytically deuterates a wide range
      of substrates with a variety of functional groups. Catalyst 4 decomposes to
      [CpPMe(3)Ir(eta(3)-CH(2)C(OH)CH(2))][OTf] (19) in acetone and to
      [CpPMe(3)IrH(CO)][OTf] (1-CO) in CH(3)OH. The catalytic H/D exchange reaction is
      not catalyzed by simple H(+) transfer, but instead proceeds by a reversible C-H
      bond activation mechanism.

PMID- 15469303
TI  - Highly effective pincer-ligated iridium catalysts for alkane dehydrogenation. DFT
      calculations of relevant thermodynamic, kinetic, and spectroscopic properties.
AB  - The p-methoxy-substituted pincer-ligated iridium complexes, (MeO-(tBu)PCP)IrH(4)
      ((R)PCP = kappa(3)-C(6)H(3)-2,6-(CH(2)PR(2))(2)) and (MeO-(iPr)PCP)IrH(4), are
      found to be highly effective catalysts for the dehydrogenation of alkanes (both
      with and without the use of sacrificial hydrogen acceptors). These complexes
      offer an interesting comparison with the recently reported bis-phosphinite
      "POCOP" ((R)POCOP = kappa(3)-C(6)H(3)-2,6-(OPR(2))(2)) pincer-ligated catalysts,
      which also show catalytic activity higher than unsubstituted PCP analogues
      (Gottker-Schnetmann, I.; White, P.; Brookhart, M. J. Am. Chem. Soc. 2004, 126,
      1804). On the basis of nu(CO) values of the respective CO adducts, the MeO-PCP
      complexes appear to be more electron-rich than the parent PCP complexes, whereas
      the POCOP complexes appear to be more electron-poor. However, the MeO-PCP and
      POCOP ligands are calculated (DFT) to show effects in the same directions,
      relative to the parent PCP ligand, for the kinetics and thermodynamics of a broad
      range of reactions including the addition of C-H and H-H bonds and CO. In
      general, both ligands favor (relative to unsubstituted PCP) addition to the 14e
      (pincer)Ir fragments but disfavor addition to the 16e complexes (pincer)IrH(2) or
      (pincer)Ir(CO). These kinetic and thermodynamic effects are all largely
      attributable to the same electronic feature: O --> C(aryl) pi-donation, from the
      methoxy or phosphinito groups of the respective ligands. DFT calculations also
      indicate that the kinetics (but not the thermodynamics) of C-H addition to
      (pincer)Ir are favored by sigma-withdrawal from the phosphorus atoms. The high
      nu(CO) value of (POCOP)Ir(CO) is attributable to electrostatic effects, rather
      than decreased Ir-CO pi-donation or increased OC-Ir sigma-donation.

PMID- 15469304
TI  - Molybdenocene trihydride complexes: influence of a [Me2Si] ansa bridge on
      classical versus nonclassical nature, stability with respect to elimination of
      dihydrogen, and acidity.
AB  - Experimental and computational studies on a series of cationic molybdenocene
      trihydride complexes, namely [Cp(2)MoH(3)]+, [(Cp(Bu)t)(2)MoH(3)]+,
      [Cp(2)MoH(3)]+, and ([Me(2)Si(C(5)Me(4))(2)]MoH(3))+, demonstrate that the most
      stable form for the ansa molybdenocene derivative is a nonclassical dihydrogen
      hydride isomer, ([Me(2)Si(C(5)Me(4))(2)]Mo(eta(2)-H(2))(H))+, whereas the stable
      forms for the non-ansa complexes are classical trihydrides, [Cp(2)Mo(H)(3)]+,
      [(Cp(Bu)t)(2)Mo(H)(3)]+, and [Cp(2)Mo(H)(3)]+. In addition to altering the
      classical versus nonclassical nature of [Cp(2)MoH(3)]+ and
      ([Me(2)Si(C(5)Me(4))(2)]Mo(eta(2)-H(2))(H))+, the [Me(2)Si] ansa bridge also
      markedly influences the stability of the complex with respect to elimination of
      H(2) and dissociation of H+. Finally, computational studies on
      ([H(2)Si(C(5)H(4))(2)]MoH(2)D)+ and ([H(2)Si(C(5)H(4))(2)]MoHD(2))+ establish
      that deuterium exhibits a greater preference than hydrogen to occupy dihydrogen
      versus hydride sites.

PMID- 15469305
TI  - Surface-aligned ion-molecule reaction on the surface of a molecular crystal CD3+
      + CD3I --> C2D5+ + DI.
AB  - An ion-molecule reaction has been observed from a condensed molecular crystal of
      CD(3)I using the time-of-flight electron-stimulated desorption ion angular
      distribution technique. The CD(3)I multilayer is produced by growth on an ordered
      substrate. The reaction occurs between CD(3)(+) ions produced by electron
      stimulated desorption and neighbor CD(3)I molecules in the topmost layer of the
      molecular crystal of CD(3)I, forming product C(2)D(5)(+) ions whose desorption
      dynamics have been measured. The normal momentum of the product ion is close to
      that of the reactant ion, suggesting that the reaction is dominated by a two-body
      collision, i.e., the momentum of the reactant CD(3)(+) ion governs the momentum
      of the product C(2)D(5)(+) ion. The ion-molecule reaction is of high cross
      section since the C(2)D(5)(+) yield is comparable to the CD(3)(+) yield. It is
      found that the yield and directionality of the emission of the C(2)D(5)(+)
      product ion is governed by the molecular order that is characteristic of the
      molecular crystal of CD(3)I. Destroying or modifying this order by using a spacer
      layer of H(2)O diminishes the C(2)D(5)(+) product ion yield relative to the
      reactant CD(3)(+) yield and broadens the ion emission directions.

PMID- 15469306
TI  - Density functional calculations of the 13C NMR chemical shifts in (9,0) single
      walled carbon nanotubes.
AB  - The electronic structure and (13)C NMR chemical shift of (9,0) single-walled
      carbon nanotubes (SWNTs) are investigated theoretically. Shielding tensor
      components are also reported. Density functional calculations were carried out
      for C(30)-capped and H-capped fragments which serve as model systems for the
      infinite (9,0) SWNT. Based on the vanishing HOMO-LUMO gap, H-capped nanotube
      fragments are predicted to exhibit "metallic" behavior. The (13)C chemical shift
      approaches a value of approximately 133 ppm for the longest fragment studied
      here. The C(30)-capped SWNT fragments of D(3d)/D(3h) symmetry, on the other hand,
      are predicted to be small-gap semiconductors just like the infinite (9,0) SWNT.
      The differences in successive HOMO-LUMO gaps and HOMO and LUMO energies, as well
      as the (13)C NMR chemical shifts, converge slightly faster with the fragment's
      length than for the H-capped tubes. The difference between the H-capped and C(30)
      capped fragments is analyzed in some detail. The results indicate that (at least
      at lengths currently accessible to quantum chemical computations) the H-capped
      systems represent less suitable models for the (9,0) SWNT because of pronounced
      artifacts due to their finite length. From our calculations for the C(30)-capped
      fragments, the chemical shift of a carbon atom in the (9,0) SWNT is predicted to
      be about 130 ppm. This value is in reasonably good agreement with experimental
      estimates for the (13)C chemical shift in SWNTs.

PMID- 15469307
TI  - Variational transition state theory as a tool to determine kinetic selectivity in
      reactions involving a valley-ridge inflection point.
AB  - Variational transition state theory has been used to calculate the kinetic
      isotope effects affecting product ratios in the reaction between (1)O(2) and d(6)
      tetramethylethylene. The minimum energy path on the potential energy surface for
      this process reaches a valley-ridge inflection point and then bifurcates leading
      to the two final products. Using canonical variational transition state theory,
      two distinct dynamical bottlenecks were located corresponding to the H- and the D
      abstraction, respectively. The calculated KIE at 263 K turns out to be 1.126.
      Analogously, a H/T KIE of 1.17 at the same temperature has been found for the
      reaction of (1)O(2) with the tritiated derivative of tetramethylethylene.

PMID- 15469308
TI  - The location of adsorbed hydrogen in graphite nanostructures.
AB  - Recent experiments suggest that the high hydrogen storage capacity in graphite
      nanostructures might be associated with adsorption on the edges. First-principles
      calculations are used to study the structure and energetics of H chemisorption on
      graphite zigzag edges. The properties of both singly and doubly hydrogenated
      edges are examined. Molecular hydrogen can dissociatively adsorb on the edge
      directly, with small activation barriers to the formation of either singly or
      doubly hydrogenated structures. A new model for the location of adsorbed H is
      proposed.

PMID- 15469309
TI  - Determination of sugar structures in solution from residual dipolar coupling
      constants: methodology and application to methyl beta-D-xylopyranoside.
AB  - We have developed methodology for the determination of solution structures of
      small molecules from residual dipolar coupling constants measured in dilute
      liquid crystals. The power of the new technique is demonstrated by the
      determination of the structure of methyl beta-d-xylopyranoside (I) in solution.
      An oriented sample of I was prepared using a mixture of C(12)E(5) and hexanol in
      D(2)O. Thirty residual dipolar coupling constants, ranging from -6.44 to 4.99 Hz,
      were measured using intensity-based J-modulated NMR techniques. These include 15
      D(HH), 4 (1)D(CH), and 11 (n)D(CH) coupling constants. The accuracy of the
      dipolar coupling constants is estimated to be < +/- 0.02 Hz. New constant-time
      HMBC NMR experiments were developed for the measurement of (n)D(CH) coupling
      constants, the use of which was crucial for the successful structure
      determination of I, as they allowed us to increase the number of fitted
      parameters. The structure of I was refined using a model in which the directly
      bonded interatom distances were fixed at their ab initio values, while 16
      geometrical and 5 order parameters were optimized. These included 2 CCC and 6 CCH
      angles, and 2 CCCC and 6 CCCH dihedral angles. Vibrationally averaged dipolar
      coupling constants were used during the refinement. The refined solution
      structure of I is very similar to that obtained by ab initio calculations, with
      11 bond and dihedral angles differing by 0.8 degrees or less and the remaining 5
      parameters differing by up to 3.3 degrees . Comparison with the neutron
      diffraction structure showed larger differences attributable to crystal packing
      effects. Reducing the degree of order by using dilute liquid crystalline media in
      combination with precise measurement of small residual dipolar coupling
      constants, as shown here, is a way of overcoming the limitation of strongly
      orienting liquid crystals associated with the complexity of (1)H NMR spectra for
      molecules with more than 12 protons.

PMID- 15469310
TI  - Slow motion, trapping, and sorting of water- and chloroform-soluble porphyrins in
      nanowells.
AB  - A two-step self-assembly procedure on smooth, aminated silica particles
      established holey monolayers. At first, single, flat-lying porphyrin tetraamides
      (A) were bound covalently, followed by the build-up of a rigid monolayer made of
      diamido bolaamphiphiles (bolas) around the porphyrin islands. "Nanowells" around
      porphyrin (A) bottoms with a uniform diameter of 2.2 nm and varying depths of
      0.6, 1.0, or 1.5 nm depending on the length of the applied bolas were thus
      obtained. Oligoethylene headgroups solubilized the particles in water, ethanol,
      and chloroform/ethanol, and two hydrogen bond chains between the secondary amide
      groups prevented swelling of the monolayer. Manganese(III) porphyrinates (B)
      migrated from the bulk solution to the bottom of the form-stable nanowells with a
      speed of about 1 pm/s and were trapped there above porphyrin (A). After isolation
      of the (A,B) particles by centrifugation or ultrafiltration, the particles were
      suspended in a chloroform solution of a chlorin (C), which was also fixated
      irreversibly on the bottom of the nanowells. The nanowells thus contained three
      different porphyrins A,B,C in a noncovalent stack. The reverse sequence A,C,B was
      built-up correspondingly, first in chloroform/ethanol, and then in water. The
      "sorting" of A,B,C and A,C,B systems was characterized by visible spectra,
      sequence-dependent fluorescence quenching, and cyclic voltammetry of the top
      component. The molecular sorting method is the first of its kind and should be
      generally useful for the production of noncovalent reaction systems on any smooth
      surface.

PMID- 15469311
TI  - Electron-deficient bonding in rhomboid rings.
AB  - The bonding environment of boron is usually thought about in terms of localized
      2c-2e/3c-2e bonding (as in diborane) or completely delocalized polyhedral bonding
      (as in B(12)H(12)(2)(-)). Recently, a number of boron compounds having a
      rhomboidal B(4) framework have been synthesized; these show an amazing variation
      in their skeletal electron count, one that cannot be interpreted in familiar
      ways. In this report, we systematically explore the origin of the range of
      electron counts in these compounds. We find that four skeletal MOs are primarily
      responsible for keeping the B(4) skeleton together. As a subunit in a
      macropolyhedral environment, termed rhombo-B(4), such an arrangement of B atoms
      deviates from Wade's rule by three electron pairs (if treated as a distorted
      arachno system derived from B(6)H(6)(2)(-)). Aided by this analysis, we examine
      the nature of bonding in Na(3)B(20), where the rhombo-B(4) unit forms linear
      chains fusing closo-B(7) units. Theory suggests that this structure requires one
      more electron per formula unit for optimal bonding. Finally, we study the nature
      of bonding in beta-SiB(3), where silicon atoms also adopt the rhomboid framework.

PMID- 15469312
TI  - Cooperative motions of protein and hydration water molecules: molecular dynamics
      study of scytalone dehydratase.
AB  - Two molecular dynamics (MD) simulations totaling 25 ns of simulation time of
      monomeric scytalone dehydratase (SD) were performed. The enzyme has a ligand
      binding pocket containing a cone-shaped alpha+beta barrel, and the C-terminal
      region covers the binding pocket. Our simulations clarified the difference in
      protein dynamics and conformation between the liganded protein and the unliganded
      protein. The liganded protein held the ligand molecule tightly and the initial
      structure was maintained during the simulation. The unliganded protein, on the
      other hand, fluctuated dynamically and its structure changed largely from the
      initial structure. In the equilibrium state, the binding pocket was fully
      solvated by opening of the C-terminal region, and the protein dynamics was
      connected with hydration water molecules entry into and release from the binding
      pocket. In addition, the cooperative motions of the unliganded protein and the
      hydration water molecules produced the path through the protein interior for
      ligand binding.

PMID- 15469313
TI  - Elastic effects behind cooperative bonding in beta-sheets.
AB  - We present extensive density functional theory calculations of the bonding
      between strands in beta-sheets. We identify a significant cooperative effect
      whereby the interaction increases in strength with the number of strands. We show
      that the effect is related to a coupling between interstrand bonding and
      intrastrand elastic properties. It is found that a direct consequence of this
      coupling is that the pitch of beta-sheets should contract with increasing number
      of strands, and we show that the effect can be observed directly in experimental
      data from the Protein Data Bank.

PMID- 15469314
TI  - Hydration of the amylopectin branch point. Evidence of restricted conformational
      diversity of the alpha-(1-->6) linkage.
AB  - The hydration behavior of a model compound for the amylopectin branch point,
      methyl 6'-alpha-maltosyl-alpha-maltotrioside, was investigated by combining
      molecular dynamics simulations in explicit water, 500 MHz NMR spectroscopy,
      including pulsed field gradient diffusion measurements, and exploratory
      multivariate data analysis. In comparison with results on a tetrasaccharide
      analogue, the study reveals that the conformational diversity of the three-bond
      alpha-(1-->6) linkage becomes quite limited in aqueous solution upon the addition
      of a fifth glucose residue that elongates the alpha-(1-->6) branch. This
      investigation reveals two plausible starch branch point structures, one that
      permits the formation of double helices and one that is adapted for
      interconnection of double helices. The apparent rigidity of the former is
      explained by the presence of water pockets/bridges in the vicinity of the branch
      point that lock the pentasaccharide structure into one conformational family that
      is able to accommodate the creation of the double-helical amylopectin structure.

PMID- 15469315
TI  - Free energy, entropy, and induced fit in host-guest recognition: calculations
      with the second-generation mining minima algorithm.
AB  - This study applies a novel computational method to study molecular recognition
      for three sets of synthetic hosts: molecular clips, molecular tweezers, and a
      synthetic barbiturate receptor. The computed standard free energies of binding
      for the 12 binding reactions agree closely with experiment and provide insight
      into the roles of configurational entropy, preorganization, and induced fit in
      the systems studied. The computed changes in configurational entropy are
      comparable in magnitude to the changes in mean potential plus solvation energy,
      and they result primarily from changes in the average width of the energy wells
      upon binding. A strong correlation is observed between the changes in
      configurational energy and configurational entropy upon binding, resulting in
      near-linear compensation analogous to classical entropy-enthalpy compensation.

PMID- 15469316
TI  - Synthesis of a C4-epi-C1-C6 fragment of FR901464 using a novel
      bromolactolization.
AB  - [reaction: see text] A synthesis of a C4-epi-C1-C6 fragment of the antitumor
      agent FR901464 is reported. The advanced intermediate prepared in this study
      contains two of the three correct stereocenters found in the C1-C6 moiety of
      FR901464. For the preparation of this intermediate, we have developed a highly
      diastereoselective bromolactolization of a delta-alkenyl ketone.

PMID- 15469317
TI  - Asymmetric synthesis and translational competence of L-alpha-(1
      cyclobutenyl)glycine.
AB  - [reaction: see text] L-alpha-(1-Cyclobutenyl)glycine (1-Cbg) was targeted as a
      potentially translatable analogue of isoleucine and valine and as a useful
      building block for peptides. An enantioselective synthesis was executed in which
      the key step was diastereoselective addition of 1-cyclobutenylmagnesium bromide
      to the sulfinimine 2b derived from (S)-t-butanesulfinimide and tert-butyl
      glyoxylate. 1-Cbg was found to substitute efficiently for isoleucine and valine,
      but not leucine, in the translation of green fluorescent protein in vitro.

PMID- 15469318
TI  - meso-Porphyrinyl-substituted porphyrin and expanded porphyrins.
AB  - [structure: see text] A series of meso-porphyrinyl-substituted expanded
      porphyrins were prepared from the 1:1 acid-catalyzed condensation reaction of 4
      porphyrinyl-2,3,5,6-tetrafluorobenzaldehyde and pyrrole.

PMID- 15469319
TI  - pi-Stacked quadruply hydrogen-bonded dimers: pi-stacking influences H-bonding.
AB  - [reaction: see text] The effects of pi-stacking on the stability of multiply
      hydrogen-bonded systems are investigated using hybrid DFT calculations on pi
      stacked quadruply H-bonded dimers of ureidopyrimidinone in its different
      tautomeric forms. Both the strengths of the hydrogen bonds and the relative
      occurrence of tautomers are influenced by pi-stacking; electrostatics and natural
      bond orbital analysis are used to explain these observations. Finally, these
      conclusions are independent of the precise nature of the multiply hydrogen-bonded
      systems, including the DNA base pairs.

PMID- 15469320
TI  - Tin-free radical cyclizations for the synthesis of 7-azaoxindoles, 7
      azaindolines, tetrahydro[1,8]naphthyridines, and tetrahydro-5H-pyrido[2,3
      b]azepin-8-ones.
AB  - [reaction: see text] Compounds containing a pyridine nucleus fused to a saturated
      nitrogen-containing ring, including 7-azaoxindoles, 7-azaindolines,
      tetrahydro[1,8]naphthyridines, and tetrahydro-5H-pyrido[2,3-b]azepin-8-ones, were
      prepared in good yield starting from various 2,6-dichloropyridines. The method
      hinges on a free-radical xanthate-mediated cyclization or intermolecular
      addition/cyclization sequence for the construction of the new fused rings.

PMID- 15469321
TI  - Highly efficient stereoconservative amidation and deamidation of alpha-amino
      acids.
AB  - [reaction: see text] An overall stereoconservative protection and deprotection
      method of amino and carboxyl groups is presented. N-Phthaloyl N'-alkyl secondary
      amides of alpha-amino acids can be generated from corresponding N-phthaloyl amino
      acids by coupling reaction of N-alkylamines using mixed anhydride method. These
      secondary amides can be transformed by thermal rearrangement of intermediate
      nitrosoamides to O-alkyl esters with retention of configuration and excellent
      yields.

PMID- 15469322
TI  - Mercuric triflate-catalyzed synthesis of 2-methylfurans from 1-alkyn-5-ones.
AB  - [reaction: see text] 2-Methylfurans were prepared by an effective cyclization of
      1-alkyn-5-ones in the presence of mercuric triflate as the catalyst under very
      mild reaction conditions with high catalytic turnover up to 100 times. Benzene,
      toluene, or dichloromethane was the solvent of choice.

PMID- 15469323
TI  - Amphotericin B as a potential probe of the physical state of vesicle membranes.
AB  - [structure: see text] The investigations described introduce a new role for a
      natural product such as amphotericin B as a potential biophysical reporter group
      to probe the physical state of a membrane. Specifically, we demonstrated that the
      K(+) efflux pattern reveals an interesting sterol dependence. This is suggested
      to be correlated to the physical state of the membrane showing high efflux in a
      vesicle membrane of intermediate fluidity.

PMID- 15469324
TI  - Convenient methods for the synthesis of ferrocene-carbohydrate conjugates.
AB  - [structure: see text] We report two methods for the attachment of mono- and
      disaccharides to one or both of the cyclopentadienyl rings in ferrocene. The
      first strategy involves the reaction in acidic media of thioglycosides with
      ferrocenemethanol or 1,1'-ferrocenedimethanol. The second method consists of the
      regiospecific catalytic cycloaddition of propargyl glycoside and azidomethyl and
      bis(azidomethyl)ferrocene leading to the 1,2,3-triazole derivatives. The inverse
      strategy was also explored. The electrochemical behavior of the synthesized
      ferrocene-containing glycoconjugates was investigated.

PMID- 15469325
TI  - Mannich-type C-nucleosidations in the 5,8-diaza-7,9-dicarba-purine family.
AB  - [structure: see text] C-Nucleosidation with cyclic iminium salts occurring under
      mild reaction conditions and affording C-nucleosides that are isosteric with N
      nucleosides of natural purines is shown to be a consistent property of the entire
      family of 2,6-(oxo or amino)-disubstituted 5,8-diaza-7,9-dicarba-purines.

PMID- 15469326
TI  - Stereoselective synthesis of multisubstituted butadienes through directed
      Mizoroki-Heck reaction and homocoupling reaction of vinyl(2-pyridyl)silane.
AB  - [reaction: see text] We have developed the homocoupling reaction of alkenyl(2
      pyridyl)silanes mediated by CuI and CsF, in which the strong directing effect of
      the 2-pyridyl group was observed. The homocoupling reaction was successfully
      integrated with the Mizoroki-Heck reaction of vinyl(2-pyridyl)silane with aryl
      halides, enabling a rapid and stereoselective synthesis of multisubstituted
      butadienes. From a relatively small compound library, it was possible to detect a
      number of fluorescent butadienes with a wide range of fluorescence color
      variations (blue to reddish-orange).

PMID- 15469327
TI  - Racemic but tropos (chirally flexible) BIPHEP ligands for Rh(I)-complexes: highly
      enantioselective ene-type cyclization of 1,6-enynes.
AB  - [reaction: see text] The tropos (chirally flexible) or atropos (chirally rigid)
      nature of BIPHEP-Rh complexes at room temperature critically depends on the
      amines complexed. The aliphatic DPEN complex is atropos, whereas the aromatic
      DABN complex is tropos. BIPHEP-Rh chirality can thus be controlled by DABN at
      room temperature. The amine-free BIPHEP-Rh complex is tropos. At 5 degrees C,
      even amine-free BIPHEP-Rh complexes are atropos and hence can be used as
      enantiopure catalysts to give high enantioselectivity in ene-type cyclization of
      1,6-enynes.

PMID- 15469328
TI  - Preparation of tertiary amides from carbamoyl chlorides and organocuprates.
AB  - [reaction: see text] Reaction of carbamoyl chlorides with cyano-Gilman cuprates
      affords tertiary amides in good to excellent yields. The reaction is general due
      to the possibility of using reagents made either from organolithium or from
      Grignard compounds. The characterization of the main side products allowed for
      the suggestion of a possible mechanism.

PMID- 15469329
TI  - General silaindene synthesis based on intramolecular reductive cyclization toward
      new fluorescent silicon-containing pi-electron materials.
AB  - [reaction: see text] The reaction of (o-silylphenyl)acetylene derivatives with
      lithium naphthalenide undergoes intramolecular reductive cyclization to produce
      various silaindene derivatives. On the basis of this methodology, a series of
      silaindene-containing pi-electron systems are synthesized that show intense blue
      to greenish-blue fluorescence.

PMID- 15469330
TI  - Ring-closing olefin metathesis of 2,2'-divinylbiphenyls: a novel and general
      approach to phenanthrenes.
AB  - [reaction: see text] The ring-closing olefin metathesis (RCM) of 2,2'
      divinylbiphenyls, using a second-generation RCM ruthenium-based catalyst, leads
      to differently substituted phenanthrenes in quantitative yield under very mild
      reaction conditions, independent of both nature and position of the groups
      present on the biphenyl moiety.

PMID- 15469331
TI  - Synthesis of AX7593, a quinazoline-derived photoaffinity probe for EGFR.
AB  - [structure: see text] The synthesis of a photoaffinity probe for EGFR is
      described. O-Alkylation of 4-(meta-azidoanilino)-6-methoxy-7-hydroxy-quinazoline
      with a protected tetraethyleneglycol linker followed by the attachment of
      tetramethylrhodamine yielded the fluorescent probe AX7593. Photoaffinity labeling
      of EGFR by AX7593 (K(b) = 280 nM) was shown to have an efficiency of 34% and to
      be competitive with the EGFR inhibitors PP2 and AG1478.

PMID- 15469332
TI  - A ring-rearrangement metathesis approach toward the synthesis of cyclopenta- and
      cyclohexa[c]indene systems.
AB  - [reaction: see text] A highly efficient synthesis of angularly fused tricyclic
      enones, cyclopenta- and cyclohexa[c]indene skeletons, has been achieved by the
      tether-directed ring-rearrangement metathesis sequence starting with readily
      accessible norbornene derivatives bearing allyl and homoallyl groups at the
      bridging carbon.

PMID- 15469333
TI  - An investigation into causes and effects of high cyanide levels in the palladium
      catalyzed cyanation reaction.
AB  - [reaction: see text] The palladium-catalyzed cyanation reaction is known to be
      sensitive to dissolved cyanide. Investigation into some causes of high levels of
      dissolved cyanide is presented here, along with a robust solution to this
      problem.

PMID- 15469334
TI  - Selective amine recognition: development of a chemosensor for dopamine and
      norepinephrine.
AB  - [reaction: see text] A boronic acid-containing coumarin aldehyde was designed and
      synthesized. The sensor binds to catecholamines such as dopamine and
      norepinephrine by forming an iminium ion with the amine as well as a boronate
      ester with the catechol. An internal hydrogen bond produces a colorimetric
      response to these analytes with good selectivity for catecholamines over simple
      amines. The fluorescence of the sensor is quenched by the catechol.

PMID- 15469335
TI  - Cp2Fe(PR2)2PdCl2 (R = i-Pr, t-Bu) complexes as air-stable catalysts for
      challenging Suzuki coupling reactions.
AB  - [reaction: see text] The use of Cp(2)Fe(PR(2))(2)PdCl(2) (R = i-Pr and t-Bu) in
      Suzuki coupling reactions were illustrated using a high throughput screening
      approach. The di-tbpfPdCl(2) catalyst was shown to be the more active catalyst
      for unactivated and sterically challenging aryl chlorides. Comparison studies
      using the commercial catalysts dppfPdCl(2), (Ph(3)P)(2)PdCl(2),
      (Cy(3)P)(2)PdCl(2), DPEPhosPdCl(2), dppbPdCl(2), dppePdCl(2), Pd(t-Bu(3)P)(2),
      and [Pd(mu-Br)(t-Bu(3)P)](2) were also done for selected cases to demonstrate the
      superior activities of di-tbpfPdCl(2) and di-isoppfPdCl(2).

PMID- 15469336
TI  - Synthesis of cyclic hemiketals and spiroketals from dioxanorbornanes.
AB  - [reaction: see text] A new method for the synthesis of substituted pyranone
      hemiketals from dioxanorbornanes via SmI(2) is described. Also reported is a
      synthesis of spiro[4.5]ketals from analogous intermediates via acid-promoted
      deprotection/ketalization.

PMID- 15469337
TI  - Synthesis of carbazoles and dibenzofurans via cross-coupling of o-iodoanilines
      and o-iodophenols with silylaryl triflates.
AB  - [reaction: see text] An efficient route to synthesize a variety of carbazoles and
      dibenzofurans has been developed. It involves the reaction of o-iodoanilines or o
      iodophenols with silylaryl triflates in the presence of CsF to afford the N- or O
      arylated products, which are subsequently cyclized using a Pd catalyst to
      carbazoles and dibenzofurans in good to excellent yields. This chemistry
      tolerates a variety of functional groups.

PMID- 15469338
TI  - Total synthesis of (-)-alpha-kainic acid by (-)-sparteine-mediated asymmetric
      deprotonation-cycloalkylation.
AB  - [reaction: see text] We report a new enantioselective synthesis of (-)-alpha
      kainic acid from d-serine methyl ester hydrochloride, based on a (-)-sparteine
      mediated asymmetric deprotonation of an intermediate carbamate that, by
      stereospecific anti S(N)'S(E)' intramolecular cycloalkylation, leads to the
      pyrrolidine ring precursor of (-)-alpha-kainic acid, in high yield and
      diastereoselectivity. The intermediate pyrrolidine was further transformed to (-)
      alpha-kainic acid in three steps.

PMID- 15469339
TI  - Syntheses of omega-hydroxy-alpha,alpha-difluoromethylphosphonates by oxacycle
      ring-opening reactions.
AB  - [reaction: see text] Oxacycle ring-opening reactions from a non-HCFC-based source
      of phosphonodifluoromethyl carbanion 1 are reported. This straightforward
      strategy opens access to a variety of primary and secondary omega-hydroxy
      alpha,alpha-difluoromethylphosphonates via one step. The syntheses of a glycerol
      monophosphate analogue and precursors to nucleoside phosphorylase inhibitors are
      described using this method.

PMID- 15469340
TI  - An efficient synthesis of beta-C-glycosides based on the conformational
      restriction strategy: Lewis acid promoted silane reduction of the anomeric
      position with complete stereoselectivity.
AB  - [reaction: see text] The reduction of glyconolactols having an anomeric carbon
      substituent by Et(3)SiH/TMSOTf proceeded with complete stereoselectivity to
      produce the corresponding beta-C-glycosides when the substrates were
      conformationally restricted in the (4)C(1)-chair form by a 3,4-O-cyclic diketal
      or a 4,6-O-benzylidene protecting group. Thus, the efficient construction of beta
      C-glycosides was achieved on the basis of the conformation restriction strategy.

PMID- 15469342
TI  - Regioselective enzymatic acylation of beta-L-2'-deoxynucleosides: application in
      resolution of beta-D/L-2'-deoxynucleosides.
AB  - [reaction: see text] A practical synthesis of beta-L-3'- and beta-L-5'-O
      levulinyl-2'-deoxynucleosides has been described for the first time through
      enzymatic acylation and/or hydrolysis processes. It is noteworthy that the
      different behavior exhibited by Pseudomonas cepacia lipase in the acylation of D-
      and L-nucleosides allows the parallel kinetic resolution of D/L-nucleosides.

PMID- 15469341
TI  - Generation of alkoxycarbenium ion pools from thioacetals and applications to
      glycosylation chemistry.
AB  - [reaction: see text] Alkoxycarbenium ions have been generated and accumulated as
      "cation pools" by the low-temperature electrochemical oxidation of alpha
      phenylthioethers. Although an unsuccessful attempt to accumulate glycosyl cations
      was made, a one-pot method for electrochemical glycosylation, which involves
      anodic oxidation of thioglycosides to generate glycosyl cation equivalents
      followed by their reactions with glycosyl acceptors, has been developed.

PMID- 15469343
TI  - Enantioselective aldol reaction of trimethoxysilyl enol ether catalyzed by
      lithium binaphtholate.
AB  - [reaction: see text] An aldol reaction of trimethoxysilyl enol ether catalyzed by
      lithium binaphtholate, in which water serves as an additive and plays a pivotal
      role in stereoselectivities, was developed. This is the first example of an aldol
      reaction of trimethoxysilyl enol ether catalyzed by a chiral base.

PMID- 15469344
TI  - Caged trans-4-hydroxy-2-nonenal.
AB  - [reaction: see text] A caged 4-hydroxy-2-nonenal (4-HNE) has been prepared and
      its photochemistry investigated. Upon photolysis, 1 releases 4-HNE in up to 100%
      yield. From these photolyses, 4-HNE could be isolated in up to 91% yield. 4-HNE
      is produced under either aerobic or anaerobic conditions. The caging strategy
      does not require prior preparation of 4-HNE and, therefore, represents a three
      step synthetic route to the bioactive enal in 48% overall yield.

PMID- 15469345
TI  - PtCl2-Catalyzed transannular cycloisomerization of 1,5-enynes: a new efficient
      regio- and stereocontrolled access to tricyclic derivatives.
AB  - [reaction: see text] Transannular PtCl(2)-catalyzed cycloisomerizations open a
      new route to cyclopropanic tricyclic systems. Ketones A or C were efficiently
      prepared from the same cycloundec-5-en-1-yne precursor B, depending on the
      substituent at the propargylic position (either benzoate or methoxy).

PMID- 15469346
TI  - Enantioselective preparation of ring-fused 1-fluorocyclopropane-1-carboxylate
      derivatives: en route to mGluR 2 receptor agonist MGS0028.
AB  - [reaction: see text] An approach to the densely functionalized fluorocyclopropane
      14, a key framework toward the synthesis of mGluR 2 receptor agonist MGS0028 (1)
      is reported. The Trost AAA reaction enantioselectively introduced the key allylic
      stereogenic center and the alpha-fluoroester moiety. Stereoselective epoxidation
      followed by intramolecular epoxide ring opening efficiently constructed the 1
      fluorocyclopropane-1-carboxylate matrix. This route can potentially be a general
      methodology for a concise, highly enantio- and stereoselective synthesis of 1
      fluorocyclopropane-1-carboxylate derivatives.

PMID- 15469347
TI  - Synthesis of a highly reactive heterocyclic reactant and its unusual
      photochemistry; mechanistic and exploratory organic photochemistry.
AB  - [reaction: see text] A unique new set of reactions has been observed in
      heterocyclic photochemistry. 2-Methyl-4,4-diphenyl-3,4-dihydropyrimidin-1(2H)-one
      has been synthesized and its photochemistry investigated. This compound has been
      found to lead to a rearranged, dimeric product arising from a unique bond
      scission process.

PMID- 15469348
TI  - Stereocontrolled synthesis of onchidins.
AB  - [structure: see text] The first total synthesis of a molecule possessing the
      stereochemistry proposed for onchidin is described. The structure synthesized
      appears to be different from that of the marine natural product.

PMID- 15469349
TI  - Efficient and selective removal of methoxy protecting groups in carbohydrates.
AB  - [reaction: see text] The selective removal from carbohydrate substrates of
      methoxy protecting groups next to hydroxy groups is reported. On treatment with
      PhI(OAc)(2)-I(2), the methoxy group is transformed into an easily removable
      acetal. The mild conditions of this methodology are compatible with many
      functional groups, and good to excellent yields are usually achieved.

PMID- 15469350
TI  - Studies toward the total synthesis of angelmicin B (hibarimicin B): synthesis of
      a model CD-D' arylnaphthoquinone.
AB  - [structure: see text] A synthesis of arylnaphthoquinone 22 corresponding to the
      CD-D' unit of angelmicin B via the Suzuki coupling of the D' arylboronic acid 15
      with the CD bromonaphthoquinone 21 is described. The mild conditions for the
      Suzuki cross-coupling leading to 22 may prove to be useful for the eventual late
      stage coupling of the two highly functionalized halves of angelmicin B.

PMID- 15469351
TI  - Highly regioselective nucleophilic carbon-carbon bond formation on furans and
      thiophenes initiated by pummerer-type reaction.
AB  - [reaction: see text] The reactions of (phenylsulfinyl)furans or -thiophenes with
      carbon nucleophiles in the presence of trifluoroacetic anhydride allowed the
      nucleophilic installation of carbon functional groups on the furan and thiophene
      nuclei with complete regioselectivity.

PMID- 15469352
TI  - Stereospecific synthesis of 1,2-cis glycosides by vinyl-mediated IAD.
AB  - [reaction: see text] Stereospecific 1,2-cis glycosylation of 2-O-vinyl
      thioglycosides, synthesized from the corresponding alcohols by Ir-catalyzed
      transvinylation with vinyl acetate, is achieved by iodine-mediated tethering of a
      range of primary and secondary carbohydrate acceptors, followed by intramolecular
      aglycon delivery (IAD). The use of such an intramolecular glycosylation strategy
      furnishes the desired alpha-gluco and beta-manno disaccharides in an entirely
      stereoselective manner.

PMID- 15469353
TI  - Preparation of peptide p-nitroanilides using an aryl hydrazine resin.
AB  - [reaction: see text] Peptide p-nitroanilides are useful compounds for studying
      protease activity; however, the poor nucleophilicity of p-nitroaniline makes
      their preparation difficult. We describe a new efficient approach for the Fmoc
      based synthesis of peptide p-nitroanilides using an aryl hydrazine resin. Mild
      oxidation of the peptide hydrazide resin yields a highly reactive acyl diazene
      that efficiently reacts with weak nucleophiles. We have prepared several peptide
      p-nitroanilides, including substrates for the Lethal Factor protease from B.
      anthracis.

PMID- 15469354
TI  - Environmentally benign synthesis of h-phosphinic acids using a water-tolerant,
      recyclable polymer-supported catalyst.
AB  - [reaction: see text] A reusable polymer-supported hydrophosphinylation catalyst
      is described for the preparation of H-phosphinic acids. The polystyrene-based
      ligand is prepared in one step from commercially available compounds. The
      polymeric catalyst generally gives good yields for a variety of substrates and is
      water- and air-tolerant, although the scope of alkenes and alkynes which can be
      employed is somewhat narrower than with our original xantphos/Pd(2)dba(3)
      catalyst.

PMID- 15469355
TI  - 5-(2-Aminoethyl)dithio-2-nitrobenzoate as a more base-stable alternative to
      Ellman's reagent.
AB  - [reaction: see text] 5-(2-Aminoethyl)dithio-2-nitrobenzoate (ADNB) reacts with
      free thiols with kinetics similar to those of Ellman's reagent but has
      dramatically improved stability under alkaline conditions, making it an excellent
      alternative to Ellman's reagent for the quantitation of thiol contents and
      enzymatic assays under basic pH conditions.

PMID- 15469356
TI  - Synthesis and study of naphthacenedione (TQ) as a photosensitizer for one
      electron oxidation of DNA.
AB  - [reaction: see text] Photosensitizers are useful for the study of one-electron
      oxidation of DNA. Most such photosensitizers absorb light in the UV spectral
      region. We report the synthesis and investigation of a 5,12-naphthacenedione (TQ)
      derivative as a DNA photosensitizer. Irradiation of a TQ-linked duplex with
      visible light results in reaction of the DNA that is characteristic of one
      electron oxidation. The results from TQ sensitization are identical, within
      experimental error, with that of a well-studied anthraquinone derivative.

PMID- 15469357
TI  - Oligonucleotide incorporation of 8-thio-2'-deoxyguanosine.
AB  - [reaction: see text] 8-Thio-2'-deoxyguanosine (SdG) is a useful analogue of the
      abundant promutagen 8-oxo-2'-deoxyguanosine (OdG). Its synthesis and DNA
      incorporation using standard phosphoramidite chemistry is reported. To prevent
      oxidation during DNA synthesis, the sulfur was protected as a 2
      (trimethylsilyl)ethyl sulfide. Subsequent treatment with TBAF yielded the desired
      8-thiocarbonyl functionality. Melting studies with SdG revealed almost equal
      stabilities of SdG:dC and SdG:dA base pairs, lending insight into the base
      pairing preferences of OdG.

PMID- 15469358
TI  - Metathesis approach to the synthesis of polyheterocyclic structures from
      oxanorbornenes.
AB  - [reaction: see text] The synthesis of stereochemically defined tri- and penta
      heterocyclic ring systems 9 and 28, respectively, via the metathesis reaction of
      substituted oxanorbornanes derived from 3 is described.

PMID- 15469359
TI  - Application of phosphine-oxazoline ligands in Ir-catalyzed asymmetric
      hydrogenation of acyclic aromatic N-arylimines.
AB  - [reaction: see text] A new class of chiral phosphine-oxazoline ligands have been
      developed. Chiral Ir complexes prepared from these ligands induced high
      enantioselectivities (66-90% ee) when applied to the asymmetric hydrogenation of
      acyclic aromatic N-arylimines.

PMID- 15469360
TI  - OBOC small-molecule combinatorial library encoded by halogenated mass-tags.
AB  - [reaction: see text] A bromine-/chlorine-containing mass-tag encoding strategy
      for a small-molecule OBOC combinatorial library is reported. The resulting MALDI
      FTMS isotope pattern of each tag clearly defines the component building blocks of
      each "hit" bead in an 1890-member demonstration library screened on-bead for
      binding against streptavidin via both enzyme-linked colorimetric and Quantum
      Dot/COPAS assays.

PMID- 15469361
TI  - Synthesis of the bicyclo[7.3.0]dodecatrienediyne core of the C-1027 chromophore.
AB  - [reaction: see text] C-1027, an extremely potent antitumor agent, is composed of
      chromophore 1 and an apoprotein. Here we report a general and efficient route to
      the exceedingly reactive bicyclo[7.3.0]dodecatrienediyne core of 1, utilizing
      selenoxide elimination and epoxide deoxygenation to build the cyclopentadiene and
      enediyne structures, respectively.

PMID- 15469362
TI  - Novel concerted fragmentation upon alcoholysis of a urazole.
AB  - [reaction: see text] Instead of yielding the expected hydrazine, alcoholysis of
      the above heterocycle results in fragmentation via a highly unusual pathway.

PMID- 15469363
TI  - Synthesis and metalation of novel fluorescent conjugated macrocycles.
AB  - [reaction: see text] Large shape-persistent conjugated macrocycles with tunable
      pore diameters in the nanometer regime were prepared by a simple, one-pot
      procedure. These new self-assembled macrocycles contain rings of 48-66 covalently
      bonded atoms and can bind multiple metal ions, forming soluble luminescent
      complexes.

PMID- 15469364
TI  - An ionic liquid-coordinated palladium complex: a highly efficient and recyclable
      catalyst for the Heck reaction.
AB  - [structure: see text] The monoquaternary product of 2,2'-biimidazole with
      iodobutane is an ionic liquid that acts as both the solvent and ligand for
      catalytic reactions. A new palladium complex was prepared by adding PdCl(2) to
      this ionic liquid to form a catalytic solution that is effective for Heck
      reactions with good recyclability.

PMID- 15469365
TI  - Access to both anomers of pectenotoxin spiroketals by kinetic spiroketalization.
AB  - [structure: see text] A concise synthesis of both AB ring spiroisomers of the
      pectenotoxins is described. The nonanomeric AB spiroketal ring system of the
      pectenotoxins-1, -2, -3, and -6 is formed under very mild, kinetic
      spiroketalization conditions, along with the anomeric isomer. Only catalytic
      asymmetric transformations were used as the source of chirality in the synthesis
      route.

PMID- 15469366
TI  - Stereocontrolled construction of either stereoisomer of 12
      oxatricyclo[6.3.1.0(2,7)]dodecanes using Prins-pinacol reactions.
AB  - [reaction: see text] 12-Oxatricyclo[6.3.1.0(2,7)]dodecanes can be efficiently
      synthesized in a stereoselective manner by Prins-pinacol reactions. By biasing
      the transition state of the Prins cyclization, it is possible to access either
      stereoisomer of this oxatricyclic ring system.

PMID- 15469367
TI  - Syntheses of the C(1-6) and C(19-24) fragments of lituarines A, B, and C.
AB  - [structure: see text] Lituarines A-C are marine natural products comprising a
      tricyclic spiroacetal bridged at C(8) and C(18) by a functionalized ester linkage
      conceptually obtained from a C(19-24) alcohol and a C(1-6) carboxylic acid whose
      oxidation level varies at C(4) and C(5). Stereoselective routes are described to
      compounds 26 and 27, fully functionalized ester fragments of lituarine A and
      lituarines B and C, respectively.

PMID- 15469368
TI  - Stereoselective synthesis of the lituarine tricyclic spiroacetal.
AB  - [reaction: see text] Oxidative cyclizations of 2-(4-hydroxybutyl)furan
      derivatives provide spirobutenolide acetals directly; on the basis of this
      methodology, we describe an asymmetric synthesis of a tricyclic spirobutenolide
      precursor to the C(7-18) fragment common to lituarines A-C.

PMID- 15469369
TI  - Synthesis of the C11-C29 fragment of amphidinolide F.
AB  - [reaction: see text] An efficient synthesis of the C(11)-C(29) fragment 31 of
      amphidinolide F has been accomplished via a diastereoselective [3 + 2]-annulation
      reaction of allylsilane 5 and ethyl glyoxylate to prepare the key tetrahydrofuran
      15 and a highly stereoselective methyl ketone aldol reaction to generate the
      C(11)-C(16) segment.

PMID- 15469370
TI  - Synthesis of azacridone A.
AB  - [reaction: see text] The first total synthesis of the only known naturally
      occurring azaacridone alkaloid (1) has been achieved in 10 steps from
      phloroglucinol. A variety of ortholithiation reactions are described, and a
      method for overcoming the originally unfavorable regiochemistry of one of them is
      provided.

PMID- 15469371
TI  - Chiral [2.2.2] dienes as ligands for Rh(I) in conjugate additions of boronic
      acids to a wide range of acceptors.
AB  - [reaction: see text] We document a series of investigations that led to new
      substituted [2.2.2]-diene ligands which display high selectivity in Rh(I)
      catalyzed conjugate addition reactions to substrates not previously examined with
      diene ligands. Moreover, we disclose an unexpected, interesting effect that
      results from the introduction of a third C=C onto the ligand scaffold (cf. 1).

PMID- 15469372
TI  - Synthesis of seven-membered ring glycals via endo-selective alkynol
      cycloisomerization.
AB  - [reaction: see text] Alkynyldiols 1 undergo cycloisomerization to the
      corresponding seven-membered cyclic enol ethers 2 under tungsten carbonyl
      catalysis. This novel transformation proceeds with good yields and virtually
      complete regioselectivity for all diastereomers of 1, favoring the product 2
      resulting from endo-mode cyclization. The unexpected regioselectivity may be
      dependent on the presence of the dioxolane structure tethering the terminal
      alkyne and diol functional groups.

PMID- 15469373
TI  - Upgrading your computer skills: the time is now.

PMID- 15469374
TI  - A differentiated practice model for school nursing.
AB  - School nursing is notable for autonomous practice and independent decision
      making. School nurses practice within a complex school health services
      environment that is subject to constant change, the influence of multiple
      stakeholders, and a chronic state of uncertain resources. Other professional
      challenges faced by school nurses are a lack of standardized entry education
      requirement, inadequate theoretical research with practice application, and
      expanding role responsibilities. Administrative restructuring of school nursing
      services using a differentiated practice model could be a method to address the
      challenges of school nurse practice. A model of differentiated school nursing
      practice is proposed as a starting point for the national school nurse audience
      to consider this alternative to the master's entry requirement. School nurse role
      responsibilities are divided among three levels of practitioners: generalist,
      master's prepared, and school nurse policy analyst. Each level features an
      increased scope of responsibility based on higher educational attainment.
      Research regarding how differentiated practice has been implemented in other
      health care settings is described. Implications for the implementation of
      differentiated practice in school health services are discussed, including the
      need for cooperation among stakeholders, possible cost considerations, and how
      school nurse education might be affected.

PMID- 15469375
TI  - The STARS program: social empowerment training for preadolescents with attention
      deficit hyperactivity disorder (ADHD).
AB  - According to the National Institutes of Health (NIH), there has been a dramatic
      increase in the number of children being diagnosed with attention deficit
      hyperactivity disorder (ADHD) in the last several years. School nursing
      interventions need to be developed, implemented, and evaluated to address
      complexities experienced by this population. The STARS curriculum (Social
      Empowerment Training and Responsibilities for Students with ADHD) is a nursing
      intervention designed to improve perceptions of scholastic competence, social
      acceptance, and behavioral conduct in preadolescents diagnosed with ADHD. It
      consists of eight sessions with the theme of social empowerment training woven
      throughout the curriculum. The support group concept, with children helping
      children, initiated dynamic conversation as the participants creatively problem
      solved and developed solutions to their difficulties.

PMID- 15469376
TI  - Second-impact syndrome.
AB  - Sports-related injuries are among the more common causes of injury in adolescents
      that can result in concussion and its sequelae, postconcussion syndrome and
      second-impact syndrome (SIS). Students who experience multiple brain injuries
      within a short period of time (hours, days, or weeks) may suffer catastrophic or
      fatal reactions related to SIS. Adolescents are particularly susceptible to the
      dangers of SIS, and current return-to-play guidelines may be too lenient to
      protect a student from SIS. Any student with signs of a concussion should receive
      medical evaluation and not be allowed to return to play in the current game or
      practice. The role of the school nurse includes being knowledgeable about
      management of head injuries and return-to-play guidelines, providing follow-up
      for athletes who have concussions, and providing education on prevention and
      management of head injuries.

PMID- 15469377
TI  - Impact of food allergies on school nursing practice.
AB  - Food allergies affect 11 million Americans, including 6-8% of children. The rate
      of peanut allergies in children doubled from 1997 to 2002. There is no cure;
      therefore, strict avoidance of the allergen is the only way to avoid a reaction.
      Fatalities are associated with delays in or lack of epinephrine administration.
      Severe reactions, called anaphylaxis, have occurred in schools. In a nationwide
      telephone survey of 400 elementary school nurses, 44% reported an increase in
      children with food allergies in their schools over the last 5 years; more than
      one third had 10 or more students with food allergies; 78% did staff training as
      a preventive strategy, with 74% developing their own training guidelines; and 90%
      stated students' epinephrine was stored in the nurse's office. Standardized
      training in food allergies as well as timely access to epinephrine is needed to
      respond appropriately to an anaphylactic reaction in the school setting.

PMID- 15469378
TI  - Evaluation of an anaphylaxis training program for unlicensed assistive personnel.
AB  - This study evaluated a training program designed to prepare unlicensed assistive
      personnel (UAP) in high school settings to recognize and respond effectively to
      an anaphylactic emergency. Subjects included 53 adults employed by a high school
      district in the San Francisco Bay Area of California. A training model was
      developed based on Bandura's theory of sources of self-efficacy. Knowledge and
      perceived self-efficacy of participants were measured before and after the
      training program to determine if a theory-based anaphylaxis recognition and
      epinephrine auto-injector training program would increase participants' knowledge
      and self-efficacy in responding to an anaphylactic emergency. Paired t tests
      revealed significant improvement in scores for both knowledge and perceived self
      efficacy following the intervention (p < .001). This theory-based training
      program offers a valuable model for other school nurses in providing knowledge
      and skill training for unlicensed assistive personnel in other health
      emergencies.

PMID- 15469379
TI  - Overweight and perceived health in Mexican American children: a pilot study in a
      central Texas community.
AB  - This study assessed actual and perceived health status of overweight Mexican
      American clients at a central Texas school-based health center in a predominantly
      Hispanic school district. It also explored the participants' interest in making
      lifestyle changes to promote a healthy weight. A medical records review indicated
      that of the Hispanic children between the ages of 7 and 12 years, 38% had a
      weight status at or above the 85th percentile. Assessments were conducted in a
      sample of these overweight Mexican American children to learn about their medical
      history, eating and activity patterns, perceived health and body size, and
      general health-risk status. Weight-related conditions, such as elevated blood
      pressure and cholesterol levels, were found in more than half the sample. Few
      consumed fruits and vegetables, and many engaged in only sedentary activities.
      The majority perceived themselves as "big," wanted to make changes in their body
      size, and wanted family members to participate in making changes with them.
      Although most of the sample were in the 97th body mass index percentile, many
      perceived themselves to be as healthy as or healthier than others. These findings
      substantiate the need to design and implement a culturally appropriate weight
      management and obesity prevention program in this community. However, the
      perception of being healthy in the presence of multiple indicators of poor health
      may pose challenges to successful intervention.

PMID- 15469380
TI  - Spyware.
AB  - School nurses access an enormous amount of information through the Internet.
      Although most avid computer users are savvy to the threat of viruses to the
      integrity of data, many who surf the Web do not know that their data and the
      functioning of their computer is at risk to another hidden threat--spyware. This
      article will describe spyware, why it is a problem, how it is transmitted to a
      personal or business computer, how to prevent spyware infestation, and how to
      delete it.

PMID- 15469381
TI  - Privacy questions from practicing school nurses.
AB  - This Question and Answer (Q&A) article addresses practice issues related to
      school health records and school nursing documentation that were posed by school
      nurses in the field. Specifically, the questions addressed concern the following:
      education records, medication privacy issues, sharing of sensitive health
      information, privacy of individual student logs, use of record access logs, and
      the use of spreadsheets and home computers for creating student records. The
      Health Insurance Portability and Accountability Act (HIPAA), the Family
      Educational Records and Privacy Act (FERPA), and other laws are addressed as
      appropriate.

PMID- 15469382
TI  - Research to reality: applying findings to practice.

PMID- 15469383
TI  - Lumps, bumps, and things that go itch in your office!

PMID- 15469384
TI  - Autophosphorylation, electrophoretic mobility and immunoreaction of oat
      phototropin 1 under UV and blue Light.
AB  - Phototropins are UV-A/blue light photoreceptors containing two flavin
      mononucleotide (FMN)-binding domains, light, oxygen and voltage (LOV)1 and LOV2,
      of which LOV2 is more sensitive toward light and more important for the
      physiological response compared with LOV1. Some physiological responses are plant
      phototropism, chloroplast migration and stomatal opening. Oat phototropin 1
      together with light-dependent autophosphorylation shows a reduced electrophoretic
      mobility and reduced immunoreaction against a heterologous antiserum; both
      effects were suggested to be caused by phosphorylation at the same sites (M.
      Salomon, E. Knieb, T. von Zeppelin and W. Rudiger [2003] Biochemistry 42, 4217
      4225). In this study, we show that both effects can be separated from each other:
      at low temperature, reduced immunoreaction preceded the mobility shift, and
      irradiation with UV-C light led to the mobility shift without the loss of
      immunoreactivity. We demonstrated that UV-C light at 280 nm, which does not match
      any absorption maximum of FMN, leads to autophosphorylation of phototropin. It is
      hypothesized that UV-C light causes differential activation of the LOV domains
      via energy transfer from aromatic amino acids.

PMID- 15469385
TI  - Calculation of singlet oxygen dose from photosensitizer fluorescence and
      photobleaching during mTHPC photodynamic therapy of MLL cells.
AB  - Predicting the therapeutic outcome of photodynamic therapy (PDT) requires
      knowledge of the amount of cytoxic species generated. An implicit approach to
      assessing PDT efficacy has been proposed where changes in photosensitizer (PS)
      fluorescence during treatment are used to predict treatment outcome. To
      investigate this, in vitro experiments were performed in which Mat-LyLu cells
      were incubated in meta-tetra(hydroxyphenyl)chlorin (mTHPC) and then irradiated
      with 652 nm light. PS concentration, fluence rate and oxygenation were
      independently controlled and monitored during the treatment. Fluorescence of
      mTHPC was monitored during treatment and, at selected fluence levels, cell
      viability was determined using a colony-formation assay. Singlet oxygen dose was
      calculated using four different models and was compared with cell survival. For
      the dose metric based on singlet oxygen-mediated PS photobleaching, a universal
      relationship between cell survival and singlet oxygen dose was found for all
      treatment parameters. Analysis of the concentration dependence of bleaching
      suggests that the lifetime of singlet oxygen within the cell is 0.05-0.25 micros.
      Generation of about 9 x 10(8) molecules of singlet oxygen per cell reduces the
      surviving fraction by 1/e.

PMID- 15469386
TI  - Prevention of ultraviolet-B radiation damage by resveratrol in mouse skin is
      mediated via modulation in survivin.
AB  - Nonmelanoma skin cancer is the most frequently diagnosed malignancy in the United
      States, and multiple exposures to solar ultraviolet (UV) radiation (particularly
      its UV-B component, 290-320 nm), is its major cause. 'Chemoprevention' by
      naturally occurring agents is being appreciated as a newer dimension in the
      management of neoplasia including skin cancer. We recently demonstrated that
      resveratrol (trans-3, 5, 4-trihydroxystilbene), an antioxidant found in grapes,
      red wines and a variety of nuts and berries, imparts protection from acute UV-B
      mediated cutaneous damages in SKH-1 hairless mice. Understanding the mechanism of
      resveratrol-mediated protection of UV responses is important. We earlier
      demonstrated that resveratrol imparts chemopreventive effects against multiple UV
      exposure-mediated modulations in (1) cki-cyclin-cdk network, and (2) mitogen
      activated protein kinase (MAPK)-pathway. This study was conducted to assess the
      involvement of inhibitor of apoptosis protein family Survivin during resveratrol
      mediated protection from multiple exposures of UV-B (180 mJ/cm(2); on alternate
      days; for a total of seven exposures) radiations in the SKH-1 hairless mouse
      skin. Our data demonstrated that topical pre-treatment of resveratrol (10
      micromol in 200 microl acetone/mouse) resulted in significant inhibition of UV-B
      exposure-mediated increases in (1) cellular proliferations (Ki-67
      immunostaining), (2) protein levels of epidermal cyclooxygenase-2 and ornithine
      decarboxylase, established markers of tumor promotion, (3) protein and messenger
      RNA levels of Survivin, and (4) phosphorylation of survivin in the skin of SKH-1
      hairless mouse. Resveratrol pretreatment also resulted in (1) reversal of UV-B
      mediated decrease of Smac/DIABLO, and (2) enhancement of UV-B-mediated induction
      of apoptosis, in mouse skin. Taken together, our study suggested that resveratrol
      imparts chemopreventive effects against UV-B exposure-mediated damages in SKH-1
      hairless mouse skin via inhibiting Survivin and the associated events.

PMID- 15469387
TI  - DNA molecular photonics.
AB  - Synthetic DNA conjugates in which one or both ends of a short duplex is capped by
      a stilbene chromophore have been prepared and characterized crystallographically.
      Selective excitation of the chromophore can be used to initiate electron transfer
      processes in which a nucleobase serves as either an electron donor or an electron
      acceptor. These processes include hole- and electron injection and hole
      migration. The dynamics of these processes and its dependence on distance,
      driving force, and base sequence have been investigated by means of femtosecond
      time-resolved spectroscopy. Duplexes with identical chromophores at both ends
      have been used to study both the dynamics of electron transfer processes and
      exciton coupling between the two chromophores by means of circular dichroism
      spectroscopy. Duplexes with different chromophores can also be used to study
      distance dependence of both electron transfer and exciton coupling.

PMID- 15469388
TI  - Self-aggregation of synthetic protobacteriochlorophyll-d derivatives.
AB  - 3(1)-Racemically pure zinc 3(1)-hydroxy-13(1)-oxo-porphyrins (zinc methyl 17,18
      dehydro-bacteriopheophorbides-d) as well as their 3(1)-demethyl form were
      prepared by modifying chlorophyll-a through oxidation by 2,3-dichloro-5,6-dicyano
      benzoquinone. From visible, circular dichroism and infrared spectral analyses,
      these synthetic pigments self-aggregated in 1%(vol/vol) tetrahydrofuran and
      cyclohexane to give large oligomers by an intermolecular bonding of 13-C=O...H
      O(3(1))...Zn(central) and pi-pi interaction of the porphyrin chromophores. The
      supramolecular structures are similar to those of the corresponding chlorins and
      a core part of extramembranous light-harvesting antennas of photosynthetic green
      bacteria. The 17,18-dehydrogenation of a chlorin to porphyrin moiety did not
      disturb its self-aggregation and the synthetic zinc porphyrins are good models
      for naturally occurring self-aggregative bacteriochlorophylls.

PMID- 15469389
TI  - Molecular targets in immune-mediated diseases: focus on rheumatoid arthritis.
AB  - There are a large number of diseases involving inappropriate activation of the
      immune system. This review focuses on one such disease, rheumatoid arthritis
      (RA). Over recent years there has been a dramatic shift in the treatment of RA,
      in which biological agents, such as monoclonal antibodies and immuno-fusion
      proteins, have offered the potential to enhance or replace conventional
      immunosuppressive therapies. This review covers some of the novel biological
      molecules currently under investigation as potential therapeutic targets in RA.
      In addition, it covers the genomic and proteomic strategies being used to
      identify potential new molecular targets for future therapies. Selectively
      blocking the immune response, in a combination approach blocking not only
      inflammation but also the adaptive memory response and tissue destruction, holds
      great promise for the treatment of RA and many other immune-mediated diseases.

PMID- 15469390
TI  - Brain-derived neurotrophic factor as a drug target for CNS disorders.
AB  - Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of
      trophic factors. BDNF is widely and abundantly expressed in the CNS and is
      available to some peripheral nervous system neurons that uptake the neurotrophin
      produced by peripheral tissues. BDNF promotes survival and differentiation of
      certain neuronal populations during development. In adulthood, BDNF can modulate
      neuronal synaptic strength and has been implicated in hippocampal mechanisms of
      learning and memory and spinal mechanisms for pain. Several CNS disorders are
      associated with a decrease in trophic support. As BDNF and its high affinity
      receptor are abundant throughout the whole CNS, and BDNF is a potent
      neuroprotective agent, this trophic factor is a good candidate for therapeutic
      treatment of some of CNS disorders. This review aims to correlate the features of
      some CNS disorders (Parkinson's disease, Alzheimer's disease, depression,
      epilepsy and chronic pain) to changes in BDNF expression in the brain. The
      cellular and molecular mechanism by which BDNF might be a therapeutic strategy
      are critically examined.

PMID- 15469391
TI  - Role of oxidative stress and inflammation in the origin of Type 2 diabetes--a
      paradigm shift.
AB  - In Type 2 diabetes the body either produces too little insulin, or does not
      respond well to it. Current pharmacological treatments, which are less than
      optimal, either target defective insulin secretion (sulfonylureas, glinides) or
      insulin resistance (metformin, thiazolidinediones). Exciting new research is now
      helping us to understand novel pathways that may contribute to defective insulin
      secretion as well as decreased response to insulin. Such pathways may explain the
      development of diabetes and associated complications (atherosclerosis and
      diabetic nephropathy). Understanding the way a cell metabolises glucose may be
      the key to understanding how cells secrete insulin and respond to it.

PMID- 15469392
TI  - STAT proteins as novel targets for cancer drug discovery.
AB  - Signal transducer and activator of transcription (STAT) proteins are latent
      cytoplasmic transcription factors that were discovered in the context of cytokine
      and growth factor signalling. Normal STAT signalling is tightly controlled with
      finite kinetics, which is in keeping with standard cellular responses. However,
      persistent STAT activation has also been observed and is frequently associated
      with malignant transformation. Constitutive activation of STAT proteins, notably
      of Stat3 and Stat5, is detected in many human tumour cells and cells transformed
      by oncoproteins that activate tyrosine kinase signalling pathways. It is well
      established that constitutively active Stat3 is one of the molecular
      abnormalities that has a causal role in oncogenesis. Aberrant Stat3 promotes
      uncontrolled growth and survival through dysregulation of gene expression,
      including cyclin D1, c-Myc, Bcl-xL, Mcl-1 and survivin genes, and thereby
      contributes to oncogenesis. Moreover, recent studies reveal that persistently
      active Stat3 induces tumour angiogenesis by upregulation of vascular endothelial
      growth factor induction, and modulates immune functions in favour of tumour
      immune evasion. Overall, studies have validated Stat3 as a novel target for
      cancer therapy, and hence provided the rationale for developing small-molecule
      Stat3 inhibitors. This review will discuss current evidence for the critical role
      of aberrant STAT signalling in malignant transformation, and examine the validity
      as well as the therapeutic potential of Stat3 as a cancer target. An update on
      the efforts to develop novel Stat3 inhibitors for therapeutic application will
      also be provided.

PMID- 15469393
TI  - Targeted treatments for cirrhosis.
AB  - The causes of hepatic scarring (fibrosis) are protean but, unchecked, all result
      in a common fate--the development of cirrhosis--with gross disruption of the
      normal liver architecture. Subsequent liver cell dysfunction and portal
      hypertension give rise to major systemic complications and premature death.
      Cirrhosis and its sequelae represent a huge, and global, healthcare burden. The
      success of liver transplantation and the development of efficacious antiviral
      regimens for hepatitis B and C should not be underestimated, but they also serve
      to highlight our current inability to manipulate the underlying fibrotic process
      in many patients with liver disease. Moreover, transplantation as a treatment is
      limited by organ availability, among other factors. The development of
      antifibrotic therapies is urgently needed and for this we require a mechanistic
      and evidence-based approach. Accumulating data from clinical and laboratory
      studies demonstrate that even advanced fibrosis and cirrhosis are potentially
      reversible. The hepatic stellate cells have been identified as the pivotal
      effector cells orchestrating the fibrotic process and, furthermore, reversibility
      appears to hinge upon their elimination. This review draws on recent scientific
      advances, and highlights emerging therapeutic interventions in liver fibrosis.

PMID- 15469394
TI  - Potassium channel subtypes as molecular targets for overactive bladder and other
      urological disorders.
AB  - Potassium channels have re-emerged as attractive targets for overactive bladder
      and other urological diseases in recent years, in part due to an enhanced
      understanding of their molecular heterogeneity, tissue distribution, functional
      roles and regulation in physiological and pathological states. Cloning and
      heterologous expression analysis, coupled with the advancement of improved high
      throughput screening techniques, have enabled expeditious identification of
      selective small-molecule openers and blockers for ATP-sensitive K+ channels, Ca2+
      activated K+ channels and voltage-dependent K+ channel-KQT-like subfamily (KCNQ)
      members, and has paved the way in the assessment of efficacy and adverse effects
      in preclinical models. This review focuses on the rationale for molecular
      targeting of K+ channels, the current status of target validation, including
      preclinical proof-of-concept studies, and provides perspectives on the
      limitations and hurdles to be overcome in realising the potential of these
      targets for diverse urological indications such as overactive bladder, erectile
      dysfunction and prostate diseases.

PMID- 15469395
TI  - Novel targets for the treatment of endometriosis.
AB  - Endometriosis is an enigmatic, debilitating disease that affects up to 15% of all
      women of reproductive age. It is characterised by pelvic pain and infertility.
      Current treatment regimens control the disease by inducing a hypoestrogenic
      state. Although the absence of circulating oestrogen levels leads to a regression
      of the disease, this hypoestrogenism also induces many unpleasant side effects.
      As such, these and other shortcomings of current drug therapies emphasise their
      limitations and the necessity for the development of novel endometriosis
      treatments. In this review, current therapies for medical management of
      endometriosis are discussed, as are their shortcomings. Potential target areas
      that may be attractive alternatives to current therapies are also reviewed.
      Emphasis is placed upon the emerging research using TNF inhibitors, their
      potential benefits over current treatment regimens and the development of future
      potential therapeutic targets.

PMID- 15469397
TI  - Inhibition of cardiac cytochrome P450: a new approach to cardiac ischaemia and
      reperfusion damage.
AB  - During reperfusion, the heart undergoes damage characterised by excessive
      production of reactive oxygen species (ROS), which may be generated by
      mitochondrial protein synthesis or the activity of cardiac cytochrome P450
      enzymes (CYPs). Chloramphenicol inhibits both mitochondrial protein synthesis and
      the activity of CYPs, and in the perfused rat model of ischaemia/reperfusion, it
      decreased the release of creatine kinase and infarct size. This cardioprotective
      effect of chloramphenicol was not associated with mitochondrial protein
      synthesis, implicating the inhibition of CYPs in the cardioprotection. The ROS
      superoxide was generated by the heart in ischaemia/reperfusion, and this
      generation was inhibited by chloramphenicol. Inhibitors of CYP2C9 with no effect
      on mitochondrial protein synthesis, such as cimetidine and sulfaphenazole, are
      also cardioprotective in the perfused rat heart. Inhibition of CYP2C9 is a
      promising approach for the treatment of myocardial infarction, and should be
      further developed.

PMID- 15469396
TI  - Regulation of MMP-9 gene expression for the development of novel molecular
      targets against cancer and inflammatory diseases.
AB  - The need to pharmacologically control the proteolytic activity of matrix
      metalloproteinases (MMPs) has been commonly acknowledged, despite its limited
      efficacy in clinical trials. Among the reasons that explain this failure is our
      limited understanding of the signals that control the expression of MMPs in
      different cell types during different pathological conditions. Thus, future
      therapies must rely on more selective approaches. With the continually increasing
      body of proof implicating MMPs in a large number of diseases, it has become a
      priority to establish the pertinence of molecules involved in the signalling
      pathways leading to the expression of these enzymes. MMP-9 is a case in point:
      its dramatic overexpression in cancer and various inflammatory conditions clearly
      points to the molecular mechanisms controlling its expression as a potential
      target for eventual rational therapeutic intervention. In this article, recent
      progress in the signalling pathways that regulate MMP-9 expression is reviewed,
      and the latest strategies to be considered in the search for a specific inhibitor
      of its expression are presented.

PMID- 15469398
TI  - Second annual GPCRs: from orphan to blockbuster.
AB  - The superfamily of G-protein-coupled receptors (GPCRs) was discussed at a recent
      Cambridge Healthtech Institute meeting. Scientists working in both academia and
      industry participated in 2 days of talks that addressed important issues related
      to the use of GPCRs as targets. The meeting delved into questions and strategies
      surrounding receptor structure, lack of knowledge about endogenous ligands, novel
      methodology for identifying compounds from high-throughput screening, the
      development process from hits to leads, and what constitutes adequate proof-of
      principle studies. This report highlights several presentations related to the
      ongoing search for more effective GPCR-targeted drug discovery efforts.

PMID- 15469399
TI  - Chemical genetics: toward the next generation of molecular medicines.

PMID- 15469401
TI  - Nucleic acid-based technologies: application amplified.

PMID- 15469402
TI  - Bioscience 2004.

PMID- 15469403
TI  - Pharmacogenomics and drug response in cardiovascular disorders.
AB  - There are a total of 17 families of drugs that are used for treating the
      heterogeneous group of cardiovascular diseases. We propose a comprehensive
      pharmacogenomic approach in the field of cardiovascular therapy that considers
      the five following sources of variability: the genetics of pharmacokinetics, the
      genetics of pharmacodynamics (drug targets), genetics linked to a defined
      pathology and its corresponding drug therapies, the genetics of physiologic
      regulation, and environmental-genetic interactions. Examples of the genetics of
      pharmacokinetics are presented for phase I (cytochromes P450) and phase II
      (conjugating enzymes) drug-metabolizing enzymes and for phase III drug
      transporters. The example used to explain the genetics of pharmacodynamics is
      glycoprotein IIIa and the response to antiplatelet effects of aspirin. Genetics
      linked to a defined pathology and its corresponding drug therapies is exemplified
      by ADRB1, ACE, CETP and APOE and drug response in metabolic syndrome. The
      examples of cytochrome P450s, APOE and ADRB2 in relation to ethnicity, age and
      gender are presented to describe genetics of physiologic regulation. Finally,
      environmental-genetic interactions are exemplified by CYP7A1 and the effects of
      diet on plasma lipid levels, and by APOE and the effects of smoking in
      cardiovascular disease. We illustrate this five-tiered approach using examples of
      cardiovascular drugs in relation to genetic polymorphism.

PMID- 15469404
TI  - Pharmacogenomics of adrenoceptors.
AB  - Adrenoceptors (ARs) consist of nine subtypes (alpha(1A)-, alpha(1B)-, alpha(1D)-,
      beta(1)-, beta(2)-, beta(3)-, alpha(2A)-, alpha(2B)- and alpha(2C)-AR), which are
      involved in a wide spectrum of physiological functions and are the site of action
      for a considerable percentage of currently prescribed therapeutics. With the
      exception of alpha(1D), all AR subtypes are polymorphic with genetic variations
      in the coding and non-coding regions. This review discusses the biochemical
      consequences of these genetic variations and their impact in receptor function,
      disease pathophysiology, and drug response. Pharmacogenomic principles that have
      been discovered are also discussed.

PMID- 15469405
TI  - Pharmacogenetics of methotrexate.
AB  - Methotrexate (MTX) has proven efficient in the treatment of a number of
      malignancies, as well as non-malignant disorders characterized by a rapid
      cellular growth. Yet some patients might develop resistance, while others could
      have toxic side effects. MTX achieves its cytotoxicity through the inhibition of
      folate-dependent enzymes, suggesting that the genes controlling their activity or
      the levels of folate cofactors can modulate drug efficacy and, thus, the
      sensitivity of a patient to MTX. Indeed, several studies, conducted mostly in
      leukemia and rheumatoid arthritis patients, have addressed the potential for
      tailoring MTX therapy based on a patient's genetics. Several genetic variants
      have been shown to have a predictive role, among which the most frequently
      studied are those of methylenetetrahydrofolate reductase and thymidylate synthase
      genes. The other candidates, as well as gene-gene interactions, which may be even
      more important for the prediction of disease outcomes than the individual gene
      effects, are also briefly discussed.

PMID- 15469406
TI  - Pharmacogenetics of irinotecan toxicity.
AB  - Irinotecan is an anticancer drug approved in combination therapy for advanced
      colorectal cancer. Severe, life-threatening toxicities can occur from irinotecan
      treatment. Although multiple genes may play a role in irinotecan activity, the
      UDP glycuronosyltransferase 1 family, polypeptide A1 (UGT1A1) enzyme has been
      strongly associated with toxicity. A common dinucleotide repeat polymorphism in
      the UGT1A1 promoter region (UGT1A1*28) has been correlated with severe toxicity
      in cancer patients receiving irinotecan-containing therapy. Prospective screening
      of patients prior to chemotherapy selection may reduce the frequency of severe
      toxicities by allowing alternate therapy selections for patients carrying the
      UGT1A1*28 polymorphism.

PMID- 15469407
TI  - MHC-bound antigens and proteomics for novel target discovery.
AB  - The MHC molecules present normal as well as disease-related and pathogen-derived
      peptides to T cells as a way of alerting the immune system of the health status
      of a cell. Proteomic technologies involving immunoaffinity purification are now
      extensively used to separate MHC complexes from their peptide cargo, and then the
      peptides are sequenced by tandem mass spectrometry. The identified peptides are
      tested as vaccine candidates for viral diseases, immunostimulants for treating
      cancer, and immune-tolerance-inducing agents for autoimmune disorders. One of the
      challenges in devising novel HLA-peptide-based immunotherapies is to decipher
      whether a therapeutic window exists between the induction of tumor immunity and
      the onset of autoimmunity, which can have dangerous sequelae. This review will
      cover these topics with an overview of the vast possibilities emerging in the
      field of proteomic analyses of MHC-bound antigens as novel targets for
      immunotherapy.

PMID- 15469408
TI  - Toward the pharmacogenomics of cystic fibrosis--an update.
AB  - Cystic fibrosis (CF) is the most common autosomal recessive disorder in
      Caucasians, with a frequency of approximately 1 in 3000 live births. The mutated
      gene is a defective chloride channel in epithelial cells, named cystic fibrosis
      transmembrane conductance regulator (CFTR). Several different protocols for the
      scanning of the entire gene have aided molecular diagnosis and improved our
      understanding of the disorder's pathophysiology, but also showed the disease's
      complexity. Therefore, CF phenotype remains difficult to predict from CFTR
      mutation data alone: several studies have suggested that additional genes could
      modulate its clinical outcome. Gene replacement therapy is still far from being
      used in patients with CF, mostly due to the difficulties with targeting the
      appropriate cells. In this review, we summarize recent advances, both in the
      pharmacological and gene therapy field, aimed for the treatment of the disease.

PMID- 15469409
TI  - Genomics, proteomics and metabonomics in toxicology: hopefully not
      'fashionomics'.
AB  - Genomics, proteomics and metabonomics are applied to toxicology either as stand
      alone technologies or in combination, with the intention of providing a more
      efficient assessment of the potential side effects of new chemical entities. Two
      different approaches are taken: a predictive/proactive strategy based on a
      statistical analogy of 'signatures' of drugs to many known toxicant gene or
      metabolite fingerprints; and a mechanistic/reactive strategy based on the in
      depth biological analysis of the gene, protein or metabolite profiles induced by
      one or a few compounds of interest. This article focuses on the advantages and
      disadvantages of these technologies, as well as the many hurdles associated with
      both these approaches in toxicology that have to be considered before applying
      them to the assessment of future drugs.

PMID- 15469410
TI  - Genetic variation in eleven phase I drug metabolism genes in an ethnically
      diverse population.
AB  - The extent of genetic variation found in drug metabolism genes and its
      contribution to interindividual variation in response to medication remains
      incompletely understood. To better determine the identity and frequency of
      variation in 11 phase I drug metabolism genes, the exons and flanking intronic
      regions of the cytochrome P450 (CYP) isoenzyme genes CYP1A1, CYP1A2, CYP2A6,
      CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5 were amplified
      from genomic DNA and sequenced. A total of 60 kb of bi-directional sequence was
      generated from each of 93 human DNAs, which included Caucasian, African-American
      and Asian samples. There were 388 different polymorphisms identified. These
      included 269 non-coding, 45 synonymous and 74 non-synonymous polymorphisms. Of
      these, 54% were novel and included 176 non-coding, 14 synonymous and 21 non
      synonymous polymorphisms. Of the novel variants observed, 85 were represented by
      single occurrences of the minor allele in the sample set. Much of the variation
      observed was from low-frequency alleles. Comparatively, these genes are variation
      rich. Calculations measuring genetic diversity revealed that while the values for
      the individual genes are widely variable, the overall nucleotide diversity of 7.7
      x 10(-4) and polymorphism parameter of 11.5 x 10(-4) are higher than those
      previously reported for other gene sets. Several independent measurements
      indicate that these genes are under selective pressure, particularly for
      polymorphisms corresponding to non-synonymous amino acid changes. There is
      relatively little difference in measurements of diversity among the ethnic
      groups, but there are large differences among the genes and gene subfamilies
      themselves. Of the three CYP subfamilies involved in phase I drug metabolism (1,
      2, and 3), subfamily 2 displays the highest levels of genetic diversity.

PMID- 15469411
TI  - Biomedical informatics: development of a comprehensive data warehouse for
      clinical and genomic breast cancer research.
AB  - The Windber Research Institute is an integrated high-throughput research center
      employing clinical, genomic and proteomic platforms to produce terabyte levels of
      data. We use biomedical informatics technologies to integrate all of these
      operations. This report includes information on a multi-year, multi-phase hybrid
      data warehouse project currently under development in the Institute. The purpose
      of the warehouse is to host the terabyte-level of internal experimentally
      generated data as well as data from public sources. We have previously reported
      on the phase I development, which integrated limited internal data sources and
      selected public databases. Currently, we are completing phase II development,
      which integrates our internal automated data sources and develops visualization
      tools to query across these data types. This paper summarizes our clinical and
      experimental operations, the data warehouse development, and the challenges we
      have faced. In phase III we plan to federate additional manual internal and
      public data sources and then to develop and adapt more data analysis and mining
      tools. We expect that the final implementation of the data warehouse will greatly
      facilitate biomedical informatics research.

PMID- 15469412
TI  - Systems literature analysis.
AB  - Systems literature analysis (SLA) is the literature-driven version of systems
      biology. It treats collections of scientific literature as a system of millions
      of interconnections between research parameters, such as genes, diseases,
      tissues, cell events, model organisms, experiment types, and reagents. SLA aims
      to replace the traditional keyword-based querying of literature databases, which
      return sorted lists of papers, with a systems-based approach that returns
      integrated networks of relationships. Major applications include literature-based
      discovery of novel targets that link, for example, previously unlinked diseases
      and phenotypes to common genes and cellular events, and experiment design.

PMID- 15469413
TI  - Rationale and study design of the CardioGene Study: genomics of in-stent
      restenosis.
AB  - BACKGROUND AND AIMS: in-stent restenosis is a major limitation of stent therapy
      for atherosclerosis coronary artery disease. The CardioGene Study is an ongoing
      study of restenosis in bare mental stents (BMS) for the treatment of coronary
      artery disease. The overall goal is to understand the genetic determinants of the
      responses to vascular injury that result in the development of restenosis in some
      patients but not in others. Gene expression profiling at transcriptional and
      translational levels provides global assessment of gene activity after vascular
      injury and mechanistic insight. Furthermore, the delineation of genetic
      biomarkers would be of value in the clinical setting of risk-stratify patients
      prior to stent therapy. Prospective risk stratification would allow for the
      rational selection of specialized treatments against the development of in-stent
      restenosis (ISR), such as drug-eluting stents. SETTING: Patients are enrolled at
      two sites in the US with high-volume cardiac catheterization facilities: the
      William Beaumont Hospital in Royal Oak, MI, USA, and the Mayo Clinic in
      Rochester, MN, USA. STUDY DESIGN: Two complementary study designs are used to
      understand the molecular mechanisms of restenosis and the genetic biomarkers
      predictive of restenosis. First, 350 patients are enrolled prospectively at the
      time of stent implantation. Blood is sampled prior to stent placement and
      afterwards at 2 weeks and 6 months. The clinical outcome of restenosis is
      determined 6 and 12 months after stent placement. The primary outcome is clinical
      restenosis at 6 months. The major secondary outcome is clinical restenosis at 12
      months. Second, a corollary case-control analysis will be carried out with the
      enrollment of an additional 250 cases with a history of recurrent restenosis
      after treatment with BMS. Controls for this analysis are derived from the
      prospective cohort. PATIENTS AND METHODS: Consecutive patients presenting to the
      cardiac catheterization laboratory are screened, informed about the study and
      enrolled after signing the consent form. Enrollment has been completed for the
      prospective cohort, and enrollment of the additional group is ongoing. A
      standardized questionnaire is used to collect clinical data primarily through
      direct patient interview to assess medical history, medication use, functional
      status, family history, environmental factors, and social history. Further data
      are abstracted from the medical charts and catheterization reports. A total of
      276 clinical variables are collected per individual at baseline, and 49 variables
      are collected at each of the 6- and 12-month follow-up visits. A Clinical Events
      Committee adjudicates clinical outcomes. Blood samples are processed at each
      clinical enrollment site using standardized operating procedures. From each blood
      sample, several aliquots are prepared and stored of peripheral blood mononuclear
      cells, granulocytes, platelets, serum, and plasma. Additionally, a portion of
      each patient's leukocytes is cryopreserved for future cell-line creation. Samples
      are frozen and shipped to the National Heart, Lung and Blood Institute (NHLBI).
      Additional materials generated in the analysis of the samples at the NHLBI are
      frozen and stored, including isolated genomic DNA, total RNA, reverse transcribed
      cDNA libraries and labeled RNA hybridization mixtures used in microarray
      analysis. Per individual in the prospective cohort, high-quality transcript
      profiles of peripheral blood mononuclear cells at each time of blood sampling are
      obtained using Affymetrix U133A microarrays (Affymetrix, Santa Clara, CA, USA).
      Per chip, this yields 495,930 features per individual per time of sampling. This
      represents expression levels for 22,283 genes per patients oer time of blood
      sampling, including 14,500 well-characterized human genes. Proteomics of plasma
      is performed with multidimensional liquid chromatography and tandem mass
      spectrometry. Protein expression is examined similarly to mRNA expression as a
      measure of gene expression. Genotyping is performed in two manners. First, those
      genes showing differential expression at the levels of mRNA and protein are
      investigated using a candidate gene approach. Specific variants in known gene
      regulatory regions, such as promoters, are sought initially, as those variants
      may explain differences in expression level. Second, a genome-wide scan is used
      to identify genetic loci that are associated with ISR. Those regions identified
      are further examined for genes that show differential expression in the mRNA
      microarray profiling or proteomics investigations. These genes are finely
      investigated for candidate SNPs and other gene variants. Complementary genomic
      and proteomic approaches are expected to be robust. Integration of data sets is
      accomplished using a variety of informatics tools, organization of gene
      expression into functional pathways, and investigation of physical maps of up-
      and downregulated sets of genes. CONCLUSIONS: The CardioGene Study is designed to
      understand ISR. Global gene and protein expression profiling define molecular
      phenotypes of patients. Well-defined clinical phenotypes will be paired with
      genomic data to define analyses aimed to achieve several goals. These include
      determining blood gene and protein expression in patients with ISR, investigating
      the genetic basis of ISR, developing predictive gene and protein biomarkers, and
      the identification of new targets for treatment.

PMID- 15469414
TI  - The effect of the farnesyl protein transferase inhibitor SCH66336 on
      isoprenylation and signalling by the prostacyclin receptor.
AB  - Like Ras, farnesylation of the IP (prostacyclin receptor) is required for its
      efficient intracellular signalling, and hence the IP represents a potential
      target for inhibition by FTIs [FTase (farnesyl protein transferase) inhibitors].
      Herein, the effect of SCH66336 on the isoprenylation and function of the human
      and mouse IPs overexpressed in human embryonic kidney 293 cells, and by the IP
      endogenously expressed in human erythroleukaemia cells, was investigated.
      SCH66336 yielded concentration-dependent decreases in IP-mediated cAMP generation
      (IC50 0.27-0.62 nM), [Ca2+]i mobilization (IC50 26.6-48.3 nM) and IP
      internalization, but had no effect on signalling by the non-isoprenylated beta2
      adrenergic receptor or b isoform of the TP (prostanoid thromboxane A2 receptor).
      Additionally, SCH66336 impaired IP-mediated crossdesensitization of TPa
      signalling (IC50 56.1 nM) and reduced farnesylation of the molecular chaperone
      protein HDJ-2 (IC50 3.1 nM). To establish whether farnesylation of the IP is
      inhibited and/or whether its 'CaaX motif' might undergo alternative
      geranylgeranylation in the presence of SCH66336, a series of chimaeric Ha
      (Harvey)-Ras fusions were generated by replacing its CaaX motif (-CVLS) with that
      of the IP (-CSLC) or, as controls, of Ki (Kirsten)-Ras 4B (-CVIM) or Rac 1 (
      CVLL). Whereas SCH66336 had no effect on Ha-RasCVLL isoprenylation in vitro or in
      whole cells, it supported alternative geranylgeranylation of Ha-RasCVIM, but
      completely impaired isoprenylation of both Ha-RasCVLS and Ha-RasCSLC. These data
      confirm that the -CSLC motif of the IP is a direct target for inhibition by the
      FTI SCH66336, and in the presence of strong FTase inhibition, the IP does not
      undergo compensatory geranylgeranylation

PMID- 15469415
TI  - Overexpression of troponin T in Drosophila muscles causes a decrease in the
      levels of thin-filament proteins.
AB  - Formation of the contractile apparatus in muscle cells requires co-ordinated
      activation of several genes and the proper assembly of their products. To
      investigate the role of TnT (troponin T) in the mechanisms that control and co
      ordinate thin-filament formation, we generated transgenic Drosophila lines that
      overexpress TnT in their indirect flight muscles. All flies that overexpress TnT
      were unable to fly, and the loss of thin filaments themselves was coupled with
      ultrastructural perturbations of the sarcomere. In contrast, thick filaments
      remained largely unaffected. Biochemical analysis of these lines revealed that
      the increase in TnT levels could be detected only during the early stages of
      adult muscle formation and was followed by a profound decrease in the amount of
      this protein as well as that of other thin-filament proteins such as tropomyosin,
      troponin I and actin. The decrease in thin-filament proteins is not only due to
      degradation but also due to a decrease in their synthesis, since accumulation of
      their mRNA transcripts was also severely diminished. This decrease in expression
      levels of the distinct thin-filament components led us to postulate that any
      change in the amount of TnT transcripts might trigger the down-regulation of
      other co-regulated thin-filament components. Taken together, these results
      suggest the existence of a mechanism that tightly co-ordinates the expression of
      thin-filament genes and controls the correct stoichiometry of these proteins. We
      propose that the high levels of unassembled protein might act as a sensor in this
      process.

PMID- 15469416
TI  - Lack of evidence for a role of TRB3/NIPK as an inhibitor of PKB-mediated insulin
      signalling in primary hepatocytes.
AB  - The protein TRB3 (tribbles 3), also called NIPK (neuronal cell death-inducible
      protein kinase), was recently identified as a protein-protein interaction partner
      and an inhibitor of PKB (protein kinase B). To explore the hypothesis that
      TRB3/NIPK might act as a negative regulator of insulin signalling in the liver,
      this protein was overexpressed by adenoviral transduction of primary cultures of
      rat hepatocytes, and various aspects of insulin action were investigated. The
      insulin-induced phosphorylation of Ser-473 and Thr-308 of PKB was found to be
      undiminished in transduced hepatocytes with a molar excess of TRB3/NIPK over PKB
      of more than 25-fold. Consistent with unimpaired insulin activation of PKB, the
      stimulation of Ser-21 and Ser-9 phosphorylation of glycogen synthase kinase 3
      alpha and -beta, and the apparent phosphorylation level of 4E-BP1 (eukaryotic
      initiation factor 4-binding protein 1), were similar in transduced and control
      hepatocytes. The induction by insulin of the mRNAs encoding glucokinase and
      SREBF1 (sterol-regulatory-element-binding factor 1) were also normal in TRB3/NIPK
      hepatocytes. In contrast, the insulin-dependent induction of these two genes, as
      well as the activation of PKB, were shown to be suppressed in hepatocytes treated
      with the lipid ether compound PIA6 (phosphatidylinositol ether lipid analogue 6),
      a recently discovered specific inhibitor of PKB. Since TRB3/NIPK was reported to
      be increased in the liver of fasting mice, the effects of glucagon,
      glucocorticoids and insulin on the level of endogenous TRB3/NIPK mRNA in primary
      hepatocytes were investigated. No significant change in mRNA level occurred under
      any of the hormonal treatments. The present study does not support the hypothesis
      that the physiological role of TRB3/NIPK might be to put a brake on insulin
      signalling in hepatocytes.

PMID- 15469418
TI  - Exploration of multilocus effects in a highly polymorphic gene, the
      apolipoprotein (APOB) gene, in relation to plasma apoB levels.
AB  - A detailed exploration of all the polymorphisms in candidate genes is required to
      better characterize the relationship between gene variability and complex traits.
      We propose a novel strategy for investigating the association between a highly
      polymorphic gene and a phenotype, by combining a multilocus genotype analysis and
      an haplotype analysis. For the multilocus genotype analysis, a data mining tool-
      termed DICE (Detection of Informative Combined Effects)--was developed to
      identify the best subset of polymorphisms that are associated--individually or in
      combination--with the phenotype. For the haplotype analysis, we used our recently
      developed method of haplotype-phenotype association to determine the most
      informative and parsimonious haplotype model fitting the data. We illustrate this
      strategy by investigating the association between twelve polymorphisms of the
      APOB gene and plasma apoB levels in 1442 European subjects. After exploring all
      main effects and interactions between polymorphisms, DICE identified the N4311S
      polymorphism as the most informative polymorphism in relation to apoB levels.
      Haplotype analysis led to the same conclusion. Additionally, DICE identified the
      E4154K (EcoRI) and the T2488T (XbaI) polymorphisms as potentially interesting.
      This selection was not modified by inclusion of the common APOE polymorphism in
      the analysis.

PMID- 15469417
TI  - Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat
      adipocytes.
AB  - The facilitative glucose transporter, GLUT4, mediates insulin-stimulated glucose
      uptake in adipocytes and muscles, and the participation of GLUT4 in the
      pathogenesis of various clinical conditions associated with obesity, visceral fat
      accumulation and insulin resistance has been proposed. Glucose uptake by some
      members of the GLUT family, mainly GLUT1, is inhibited by flavonoids, the natural
      polyphenols present in fruits, vegetables and wine. Therefore it is of interest
      to establish if these polyphenolic compounds present in the diet, known to be
      effective antioxidants but also endowed with several other biological activities
      such as protein-tyrosine kinase inhibition, interfere with GLUT4 function. In the
      present study, we show that three flavonoids, quercetin, myricetin and catechin
      gallate, inhibit the uptake of methylglucose by adipocytes over the concentration
      range of 10-100 microM. These three flavonoids show a competitive pattern of
      inhibition, with K(i)=16, 33.5 and 90 microM respectively. In contrast, neither
      catechin nor gallic acid inhibit methylglucose uptake. To obtain a better
      understanding of the interaction among GLUT4 and flavonoids, we have derived a
      GLUT4 three-dimensional molecular comparative model, using structural co
      ordinates from a GLUT3 comparative model and a mechanosensitive ion channel [PDB
      (Protein Data Bank) code 1MSL] solved by X-ray diffraction. On the whole, the
      experimental evidence and computer simulation data favour a transport inhibition
      mechanism in which flavonoids and GLUT4 interact directly, rather than by a
      mechanism related to protein-tyrosine kinase and insulin signalling inhibition.
      Furthermore, the results suggest that GLUT transporters are involved in flavonoid
      incorporation into cells.

PMID- 15469419
TI  - Contribution of chromosome 1q21-q23 to familial combined hyperlipidemia in
      Mexican families.
AB  - Familial combined hyperlipidemia (FCHL) is the most common familial dyslipidemia,
      with a prevalence of 1-2% in the general population. A major locus for FCHL has
      been mapped to chromosome 1q21-q23 in Finnish, Chinese, German and US families.
      We studied seven extended Mexican families with 153 members, including 64
      affected subjects. A total of 11 markers were genotyped, including D1S104 which
      has been linked to FCHL in other studies. Two point linkage analysis for the FCHL
      phenotype, and for the elevated triglyceride (TG) trait, allowing for
      heterogeneity, gave a maximum HLOD of 1.67 (alpha = 0.49) and 1.93 (alpha = 0.43)
      at D1S2768 (2.69 cM proximal to D1S104) respectively. Heterogeneity and non
      parametric (NPL) multipoint analyses for the FCHL phenotype and the TG trait
      showed maximum HLODs of 1.27 (alpha = 0.46) and 1.64 (alpha = 0.38), and NPLs of
      4.00 (P = 0.0001) and 3.68 (P = 0.0003) near D1S2768, respectively. In addition,
      analysis of four candidate genes putatively involved in the expression of FCHL
      showed no evidence of linkage for the LCAT gene or the APOA1/C3/A4/A5 gene
      cluster. However, we cannot exclude the participation of these genes, or the LIPC
      and LPL genes, as minor susceptibility loci in the expression of FCHL, or the TG
      or elevated total cholesterol (TC) traits in our families. In conclusion, our
      data confirm the involvement of a major susceptibility locus on chromosome 1q21
      q23 in FCHL Mexican families, consistent with findings in other populations.

PMID- 15469420
TI  - Compound haplotypes at Xp11.23 and human population growth in Eurasia.
AB  - To investigate patterns of diversity and the evolutionary history of Eurasians,
      we have sequenced a 2.8 kb region at Xp11.23 in a sample of African and Eurasian
      chromosomes. This region is in a long intron of CLCN5 and is immediately flanked
      by a highly variable minisatellite, DXS255, and a human-specific Ta0 LINE.
      Compared to Africans, Eurasians showed a marked reduction in sequence diversity.
      The main Euro-Asiatic haplotype seems to be the ancestral haplotype for the whole
      sample. Coalescent simulations, including recombination and exponential growth,
      indicate a median length of strong linkage disequilibrium, up to approximately 9
      kb for this area. The Ka/Ks ratio between the coding sequence of human CLCN5 and
      its mouse orthologue is much less than 1. This implies that the region sequenced
      is unlikely to be under the strong influence of positive selective processes on
      CLCN5, mutations in which have been associated with disorders such as Dent's
      disease. In contrast, a scenario based on a population bottleneck and exponential
      growth seems a more likely explanation for the reduced diversity observed in
      Eurasians. Coalescent analysis and linked minisatellite diversity (which reaches
      a gene diversity value greater than 98% in Eurasians) suggest an estimated age of
      origin of the Euro-Asiatic diversity compatible with a recent out-of-Africa model
      for colonization of Eurasia by modern Homo sapiens.

PMID- 15469421
TI  - Y chromosome and mitochondrial DNA variation in Lithuanians.
AB  - The genetic composition of the Lithuanian population was investigated by
      analysing mitochondrial DNA hypervariable region 1, RFLP polymorphisms and Y
      chromosomal biallelic and STR markers in six ethnolinguistic groups of
      Lithuanians, to address questions about the origin and genetic structure of the
      present day population. There were no significant genetic differences among
      ethnolinguistic groups, and an analysis of molecular variance confirmed the
      homogeneity of the Lithuanian population. MtDNA diversity revealed that
      Lithuanians are close to both Slavic (Indo-European) and Finno-Ugric speaking
      populations of Northern and Eastern Europe. Y-chromosome SNP haplogroup analysis
      showed Lithuanians to be closest to Latvians and Estonians. Significant
      differences between Lithuanian and Estonian Y chromosome STR haplotypes suggested
      that these populations have had different demographic histories. We suggest that
      the observed pattern of Y chromosome diversity in Lithuanians may be explained by
      a population bottleneck associated with Indo-European contact. Different Y
      chromosome STR distributions in Lithuanians and Estonians might be explained by
      different origins or, alternatively, be the result of some period of isolation
      and genetic drift after the population split.

PMID- 15469422
TI  - Mitochondrial DNA diversity in tribal and caste groups of Maharashtra (India) and
      its implication on their genetic origins.
AB  - Genetic relationships among caste-groups are not uniform across the geographical
      regions of India. Many anthropologists have speculated on the tribal origin of
      some caste groups in Maharashtra and other states of India. To test this
      hypothesis, we used neutral mtDNA markers to study genetic relatedness among
      tribal and caste groups from Maharashtra. Descriptive statistics such as
      nucleotide diversity, gene diversity and average mismatches were found to be of
      the same magnitude. Phylogenetic network analysis exhibited a star-like expansion
      that may date back to the peopling of Eurasia, approximately 50,000 year ago. The
      reconstruction of mtDNA haplogroups showed that both the caste and tribal
      populations share similar branches of the tree. Also, the coalescence age
      estimation of caste and tribal populations suggests the persistence of maternal
      lineages with their root in early late Pleistocene. Our mtDNA analyses show some
      preliminary and significant evidence for the origin of prehistoric tribal and
      hierarchical caste societies of Maharashtra.

PMID- 15469423
TI  - Inferring the most likely geographical origin of mtDNA sequence profiles.
AB  - In a number of practical cases it is important to determine the likely
      geographical origin of an individual or a biological sample. A dead body, old
      bones or a sample of semen may be available. Information on where the sample
      might come from can assist investigation or research. The first part of this
      paper is independent of specific data structure. We formulate the problem as a
      classification problem. Bayes' theorem allows different sources of information or
      data to be reconciled conveniently. The main part of the paper involves high
      dimensional data for which simple, standard methods are not likely to work
      properly. Mitochondrial DNA (mtDNA) data is a typical example of such data. We
      propose a procedure involving essentially two steps. First, principal component
      analysis is used to reduce the dimension of the data. Next, quadratic
      discriminant analysis performs the actual classification. A cross validation
      procedure is implemented to select the optimal number of principal components.
      The importance of using separate data sets for model fitting and testing is
      emphasized. This method distinguishes well between individuals with a self
      reported European (Icelandic or German) origin and SE Africans. In this case the
      error rate is 2.0%.

PMID- 15469424
TI  - Genetic dissection of human stature in a large sample of multiplex pedigrees.
AB  - Recently, we reported a whole genome scan on a sample of 630 Caucasian subjects
      from 53 human pedigrees. Several genomic regions were suggested to be linked to
      height. In an attempt to confirm the identified genomic regions, as well as to
      identify new genomic regions linked to height, we conducted a whole genome
      linkage study on an extended sample of 1,816 subjects from 79 pedigrees, which
      includes the 53 pedigrees containing the original 630 subjects from our previous
      whole genome study and an additional 128 new subjects, and 26 further pedigrees
      containing 1,058 subjects. Several regions achieved suggestive linkage signals,
      such as 9q22.32 [MLS (multipoint LOD score) = 2.74], 9q34.3 [MLS = 2.66], Xq24
      [two-point LOD score = 2.64 at the marker DXS8067], and 7p14.2 [MLS = 2.05]. The
      importance of the above regions is supported either by other whole genome studies
      or by candidate genes within these regions relevant to linear growth or
      pathogenesis of short stature. In addition, this study has tentatively confirmed
      the Xq24 region's linkage to height, as this region was also detected in the
      previous whole genome study. To date, our study has achieved the largest sample
      size in the field of genetic linkage studies of human height. Together with the
      findings of other studies, the current study has further delineated the genetic
      basis of human stature.

PMID- 15469425
TI  - Commingling analysis of intraocular pressure and glaucoma in an older Australian
      population.
AB  - PURPOSE: To test the hypothesis of a major genetic determinant of intraocular
      pressure (IOP) under the mixed genetic model in a defined population, and to
      elucidate the relationship between IOP and glaucoma. METHODS: IOP was measured in
      3654 persons attending the Blue Mountains Eye Study. A commingling analysis on
      IOP was performed using a new program, SKUDRIVER. The goodness of fit of 1-, 2-
      and 3-distribution models was measured. This was repeated after the glaucoma
      cases had been removed from the dataset, and further repeated on the glaucoma
      cases in the dataset. RESULTS: The best model was 3-distribution with no evidence
      for Hardy-Weinberg disequilibrium. The proportion of variance explained by this
      major effect was 0.18. When glaucoma cases were removed, the best model had 2
      distributions. There was no evidence of admixture in glaucoma patients.
      CONCLUSIONS: The findings of this study are consistent with the presence of a
      major gene accounting for 18% of the variance of IOP, which could therefore
      influence the risk of glaucoma, in this population. These findings suggest
      methods of optimizing strategies for family and association studies to identify
      quantitative trait loci for IOP. No evidence for distinct IOP-dependent and IOP
      independent subgroups of glaucoma was found.

PMID- 15469426
TI  - Methods for testing familial aggregation of diseases in population-based samples:
      application to Hodgkin lymphoma in Swedish registry data.
AB  - We use data on lymphoma in families of Hodgkin lymphoma (HL) cases from the
      Swedish Family Cancer Database (Hemminki et al. 2001) to illustrate survival
      methods for detecting familial aggregation in first degree relatives of case
      probands compared to first degree relatives of control probands, from registries
      that permit sampling of all cases. Because more than one case may occur in a
      given family, the first degree relatives of case probands are not necessarily
      independent, and we present procedures that allow for such dependence. A
      bootstrap procedure also accommodates matching of case and control probands by
      resampling the matching clusters, defined as the combined set of all first degree
      relatives of the matched case and control probands. Regarding families as
      independent sampling units leads to inferences based on "sandwich variance
      estimators" and accounts for dependencies from having more than one proband in a
      family, but not for matching. We compare these methods in analysis of familial
      aggregation of HL and also present simulations to compare survival analyses with
      analyses of binary outcome data.

PMID- 15469427
TI  - Novel HMBS founder mutation and significant intronic polymorphism in Spanish
      patients with acute intermittent porphyria.
AB  - Acute intermittent porphyria (AIP) is an autosomal dominant disorder of heme
      biosynthesis, caused by a partial deficiency of hydroxymethylbilane synthase
      (HMBS). Knowledge of the nature of the HMBS mutations causing AIP in Spanish
      families is very limited. Here we report a novel 669_698del of the HMBS gene in
      twenty-two individuals from five independent Spanish AIP families, settled in
      Murcia (southeastern region of Spain). All mutation carriers shared a common
      disease associated haplotype indicating an ancestral founder effect.
      Identification of the 669_698del founder mutation allowed rapid and simple
      molecular diagnosis of AIP in families from this region in Spain. In addition,
      771 + 58C>T in intron 12 on the non-669_698del allele was identified in six AIP
      patients, which promoted homozygous AIP misdiagnosis.

PMID- 15469428
TI  - Estimated frequency of genetic and nongenetic causes of congenital idiopathic
      cerebral palsy in west Sweden.
AB  - Mathematical analysis of prenatal and perinatal risk factors was performed on the
      first 681 published cases of idiopathic congenital cerebral palsy (born 1959
      1970) in the west Swedish population-based cerebral palsy (CP) study. Analysis
      indicates that an estimated 40% of etiologically undiagnosed cases of CP in the
      community (48% of those born at term and 24% of those born prematurely) are
      genetically caused. These proportions of genetic causation are no less in CP than
      in idiopathic mental retardation. Genetic causes account for 60% of maturely born
      hemiplegics, 45% of maturely born spastic diplegics, 32% of premature spastic
      diplegics and virtually all cases of pure ataxia. About 23% of CP cases in the
      community have suffered nongenetic brain damage in accordance with the two-stage
      model. The residue of 37% is characterized by a single risk factor, usually
      perinatal.

PMID- 15469429
TI  - Endosomal membrane traffic: convergence point targeted by Mycobacterium
      tuberculosis and HIV.
AB  - Inhibition of phagolysosome biogenesis in infected macrophages is a classical
      pathogenesis determinant of Mycobacterium tuberculosis. In this review we
      primarily cover the cellular mechanisms of M. tuberculosis phagosome maturation
      arrest. A detailed picture is beginning to emerge, involving regulators of
      membrane trafficking in mammalian cells and phagosomal interactions with
      endosomal organelles and the trans-Golgi network. We also present a hypothesis
      that overlaps may exist between the mycobacterial interference with the host cell
      membrane trafficking processes and the targeting of the late endosomal sorting
      machinery by HIV during viral budding in macrophages. We propose that
      interference with the endosomal sorting machinery contributes to the synergism
      between the two significant human diseases--AIDS and tuberculosis.

PMID- 15469430
TI  - Immunity to vacuolar pathogens: what can we learn from Legionella?
AB  - Intracellular pathogens can manipulate host cellular pathways to create
      specialized organelles. These pathogen-modified vacuoles permit the survival and
      replication of bacterial and protozoan microorganisms inside of the host cell. By
      establishing an atypical organelle, intracellular pathogens present unique
      challenges to the host immune system. To understand pathogenesis, it is important
      to not only investigate how these organisms create unique subcellular
      compartments, but to also determine how mammalian immune systems have evolved to
      detect and respond to pathogens sequestered in specialized vacuoles. Recent
      studies have identified genes in the respiratory pathogen Legionella pneumophila
      that are essential for establishing a unique endoplasmic reticulum-derived
      organelle inside of mammalian macrophages, making this pathogen an attractive
      model system for investigations on host immune responses that are specific for
      bacteria that establish vacuoles disconnected from the endocytic pathway. This
      review will focus on the host immune response to Legionella and highlight areas
      of Legionella research that should help elucidate host strategies to combat
      infections by intracellular pathogens.

PMID- 15469431
TI  - Salmonella-induced macrophage death: multiple mechanisms, different outcomes.
AB  - The facultative intracellular pathogen Salmonella enterica triggers programmed
      cell death in macrophages. The close examination of this phenomenon has revealed
      an unusually complex picture involving diverse mechanisms that lead to different
      types of programmed cell death. It appears that the outcome of the interaction of
      salmonella with macrophages depends on the relative contribution of two type III
      protein secretion systems, in conjunction with the stimulation of innate immunity
      outputs through conserved determinants collectively known as 'pathogen-associated
      molecular patterns' (PAMPs). These interactions result in a breakdown of the
      balance between survival and pro-apoptotic cellular pathways, which eventually
      leads to macrophage cell death. The relative significance for the infection
      process of the different types of macrophage cell death triggered by salmonella
      remains to be established.

PMID- 15469432
TI  - Disabling surveillance: bacterial type III secretion system effectors that
      suppress innate immunity.
AB  - Many Gram-negative bacterial pathogens of plants and animals are dependent on a
      type III protein secretion system (TTSS). TTSSs translocate effector proteins
      into host cells and are capable of modifying signal transduction pathways. The
      innate immune system of eukaryotes detects the presence of pathogens using
      specific pathogen recognition receptors (PRRs). Plant PRRs include the FLS2
      receptor kinase and resistance proteins. Animal PRRs include Toll-like receptors
      and nucleotide-binding oligomerization domain proteins. PRRs initiate signal
      transduction pathways that include mitogen-activated protein kinase (MAPK)
      cascades that activate defence-related transcription factors. This results in
      induction of proinflammatory cytokines in animals, and hallmarks of defence in
      plants including the hypersensitive response, callose deposition and the
      production of pathogenesis-related proteins. Several type III effectors from
      animal and plant pathogens have evolved to counteract innate immunity. For
      example, the Yersinia YopJ/P cysteine protease and the Pseudomonas syringae
      HopPtoD2 protein tyrosine phosphatase inhibits defence-related MAPK kinase
      activity in animals and plants respectively. Thus, type III effectors can
      suppress signal transduction pathways activated by PRR surveillance systems.
      Understanding targets and activities of type III effectors will reveal much about
      bacterial pathogenicity and the innate immune system in plants and animals.

PMID- 15469433
TI  - Analysis of the mechanisms of Salmonella-induced actin assembly during invasion
      of host cells and intracellular replication.
AB  - Salmonella enterica serovar Typhimurium (S. typhimurium) induces actin assembly
      both during invasion of host cells and during the course of intracellular
      bacterial replication. In this study, we investigated the involvement in these
      processes of host cell signalling pathways that are frequently utilized by
      bacterial pathogens to manipulate the eukaryotic actin cytoskeleton. We confirmed
      that Cdc42, Rac, and Arp3 are involved in S. typhimurium invasion of HeLa cells,
      and found that N-WASP and Scar/WAVE also play a role in this process. However, we
      found no evidence for the involvement of these proteins in actin assembly during
      intracellular replication. Cortactin was recruited by Salmonella during both
      invasion and intracellular replication. However, RNA interference directed
      against cortactin did not inhibit either invasion or intracellular actin
      assembly, although it resulted in increased cell spreading and a greater number
      of lamellipodia. We also found no role for either the GTPase dynamin or the
      formin family member mDia1 in actin assembly by intracellular bacteria.
      Collectively, these data provide evidence that signalling pathways leading to
      Arp2/3-dependent actin nucleation play an important role in S. typhimurium
      invasion, but are not involved in intracellular Salmonella-induced actin
      assembly, and suggest that actin assembly by intracellular S. typhimurium may
      proceed by a novel mechanism.

PMID- 15469434
TI  - Identification of Salmonella typhimurium genes responsible for interference with
      peptide presentation on MHC class I molecules: Deltayej Salmonella mutants induce
      superior CD8+ T-cell responses.
AB  - Salmonella-derived epitopes are presented on MHC molecules by antigen-presenting
      cells, and both CD4+ and CD8+ T cells participate in protective immunity to
      Salmonella. Therefore, mechanisms that allow Salmonella to escape specific immune
      recognition are likely to have evolved in this bacterial pathogen. To identify
      Salmonella genes, which potentially interfere with the MHC class I (MHC-I)
      presentation pathway, Tn10d transposon mutagenesis was performed. More than 3000
      mutants, statistically covering half of the Salmonella genome, were individually
      screened for altered peptide presentation by infected macrophages. Two mutants
      undergoing enhanced antigen presentation by macrophages were identified, carrying
      a Tn10d insertion in the yej operon. This phenotype was validated by specific
      inactivation and complementation experiments. In accordance with their enhanced
      MHC-I presentation phenotype, we showed that (i) specific CD8+ T cells were
      elicited at a higher level in mice, in response to immunization with yej mutants
      compared to their parental strain in two different experimental settings; and
      (ii) yej mutants were superior vaccine carriers for heterologous antigens
      compared to the parental strain in a tumour model.

PMID- 15469435
TI  - Salmonella enterica serovar Typhimurium interaction with dendritic cells: impact
      of the sifA gene.
AB  - Salmonella enterica serovar Typhimurium (S. Typhimurium) and several mutant
      derivatives were able to enter efficiently murine bone marrow-derived dendritic
      cells using mechanisms predominantly independent of the Salmonella pathogenicity
      island 1 type III secretion system. The levels of intracellular bacteria did not
      increase significantly over many hours after invasion. Using fluid endocytic
      tracers and other markers, S. Typhimurium-containing vacuoles (SCVs) were
      physically distinguishable from early endocytic compartments. Fifty to eighty per
      cent of SCVs harbouring wild-type S. Typhimurium or aroA, invH and ssaV mutant
      derivatives were associated with late endosome markers. In contrast, S.
      Typhimurium sifA was shown to escape the SCVs into the cytosol of infected
      dendritic cells. S. Typhimurium aroC sifA was more efficient than S. Typhimurium
      aroC in delivering a eukaryotic promoter-driven green fluorescent protein
      reporter gene for expression in dendritic cells. In contrast, S. Typhimurium aroC
      sifA did not detectably increase the efficiency of MHC class I presentation of
      the model antigen ovalbumin to T cells compared to a similar aroC derivative.
      Mice infected with the S. Typhimurium aroC sifA expressing ovalbumin did not
      develop detectably enhanced levels of cytotoxic T cell or interferon-gamma
      production compared to S. Typhimurium aroC derivatives.

PMID- 15469436
TI  - Candida albicans and Streptococcus salivarius modulate IL-6, IL-8, and TNF-alpha
      expression and secretion by engineered human oral mucosa cells.
AB  - We investigated the involvement of oral epithelial cells via two cytokines (IL-6
      and TNF-alpha) and one chemokine (IL-8) in local defences against live yeast
      (Candida albicans) and bacteria (Streptococcus salivarius) using an engineered
      human oral mucosa model. We report that the yeast changed from the blastospore to
      the hyphal form and induced significant tissue disorganization at later contact
      periods (24 and 48 h) compared to the bacteria. However, this effect did not
      reduce the viability or total number of epithelial cells. Gene activation
      analyses revealed that IL-6, IL-8 and TNF-alpha mRNA levels rose in tissues in
      contact with live C. albicans or S. salivarius. Gene activation was followed by
      an upregulation of protein secretion. IL-6 levels were higher after contact with
      C. albicans than with S. salivarius. IL-8 levels after contact with S. salivarius
      were higher than with C. albicans. Our study suggests that S. salivarius is more
      efficient at inducing proinflammatory mediator release than C. albicans. These
      results provide additional evidence for the contribution of oral epithelial cells
      to the inflammatory response against fungi and bacteria.

PMID- 15469437
TI  - Enteropathogenic Escherichia coli EspF is targeted to mitochondria and is
      required to initiate the mitochondrial death pathway.
AB  - Enteropathogenic Escherichia coli (EPEC) is a causative agent of infant diarrhoea
      in developing countries. The EspF protein is the product of the espF gene found
      on the locus of enterocyte effacement, the key pathogenicity island carried by
      EPEC and enterohemorrhagic E. coli. EspF is injected from adherent EPEC into host
      cells via a type III secretion system and was previously shown to induce
      apoptotic cell death and to be required for disruption of host intestinal barrier
      function. In this work, we show by immunofluorescence and fractionation studies
      that EspF is targeted to host mitochondria. The N-terminal region of EspF serves
      as a mitochondrial import signal and, when expressed within cells, can target
      hybrid green fluorescent protein to mitochondria. Assessment of mitochondrial
      membrane potential in infected epithelial cells indicated that EspF plays a role
      in the mitochondrial membrane permeabilization induced by EPEC infection.
      Furthermore, EspF was associated with the release of cytochrome c from
      mitochondria into the cytoplasm and with caspase-9 and caspase-3 cleavage. These
      findings indicate a role for EspF in initiating the mitochondrial death pathway.

PMID- 15469440
TI  - Association amongst factors thought to be important by instructors in dental
      education and perceived effectiveness of these instructors by students.
AB  - It is hypothesised that dental educators have perceptions of their roles as
      effective teachers. It is expected that subject matter expertise would be amongst
      the components of such personal philosophies of education, but it is unclear
      whether faculty member self-perceptions carry over into student ratings of
      instructors' effectiveness. A 20-item survey of 'Teaching Characteristics' was
      completed by 86% of full-time and 64% of the part-time faculty members at the
      University of the Pacific. Respondents distributed 100 points amongst the
      descriptions of what makes an effective instructor. The responses were factor
      analysed, resulting in four general faculty 'types' that explained about 50% of
      the variance in ratings: expert, enthusiast, judicial and good soldier. Student
      ratings for the 2 years running up to the date of the survey administration were
      used to gauge student perceptions of instructor effectiveness. Faculty members
      who placed emphasis on expertise as key to being a good instructor received
      significantly lower ratings for teacher effectiveness from students than did
      other faculty members. Faculty members who conceived their roles as motivating
      students, explaining difficult concepts, displaying interest in the subject,
      showing compassion and caring, and being proactive tended to receive high ratings
      for teaching effectiveness from students.

PMID- 15469441
TI  - Assessment and evaluation of individual prerequisites for dental education.
AB  - Since 2001 the School of Dentistry of Malmo University in Sweden has used an
      alternative admissions procedure based on results of an investigation supported
      by the Swedish Council for the Renewal of Undergraduate Education. The
      investigation concerned possibilities of predicting dental school performance on
      the basis of an interview, as well as tests of general intelligence, spatial
      ability, manual dexterity, empathy and social competence. Two groups of incoming
      students were followed from start to completion of their training. Significant
      relationships were found between (i) number of course examinations failed and
      poor results on interviews, as well as low scores on intelligence, spatial
      ability, and a test of spatial-manual ability, (ii) good results in a pre
      clinical course in cavity preparation and high scores on spatial ability, (iii)
      assessments of high social competence during training and good results on
      interviews, as well as high scores on empathy and non-verbal intelligence.
      Dropout from the study programme could not be predicted, possibly due to the
      varying reasons for it.

PMID- 15469442
TI  - Impact of teaching requirements for students on the activity of a university
      dental hospital.
AB  - OBJECTIVES: This study aimed at investigating the influence of teaching
      requirements on the clinical activity of a dental hospital. METHOD: The annual
      clinical activity of seven classes of fifth-year students (n = 294) was monitored
      between 1994 and 2001 within the conservative dentistry and endodontic
      departments of a French dental hospital. The variables chosen were: (i) the mean
      number of procedures performed per student, and (ii) the proportion of different
      types of treatment within the global activity (i.e. endodontic treatment,
      anterior, and posterior restorations). These data were analysed in relation to
      changes in student assessment criteria over time. RESULTS: Quantitative clinical
      teaching requirements were removed for the academic year 1998-99 and student
      clinical activity subsequently decreased by 32.7%, going from 51.9 +/- 12.2
      dental procedures on average per student in 1997-98, to 29.1 +/- 7.2 in 2000-01.
      The mean number of patients treated per student also declined significantly
      during this period. The size of the minimum clinical requirement altered over the
      years prior to being removed altogether and a positive correlation existed
      between the volume of activity and the minimum requirement over this time. The
      types of treatment provided changed independently from the assessment criteria
      over the study period. There was a decrease in the percentage of amalgams placed
      and an increase in the number of posterior composites. A negative correlation
      existed between the evolution of these two types of treatment. CONCLUSION: This
      study demonstrates that the clinical activity of a department in a dental
      teaching hospital is directly related to the assessment criteria fixed by the
      university. This may have repercussions for hospital services.

PMID- 15469443
TI  - Students' attitudes to digital radiography and measurement accuracy of two
      digital systems in connection with root canal treatment.
AB  - The aim of this study was to evaluate students' attitudes towards digital
      radiography and measurement accuracy in digital images recorded with a CCD-sensor
      and a photostimulable phosphor (PSP) plate radiography system in connection with
      root canal treatment. Thirty-one dental students participated in an endodontic
      course. Two single-rooted teeth were assigned at random to two receptors for
      digital radiographic examination, either (i) the RVG-ui CCD sensor or (ii) the
      Digora PSP plate system. After the endodontic treatment had been completed for
      the first tooth, the student filled in a questionnaire on their use of the
      digital system. Thereafter, the students switched radiography system and repeated
      the procedure for the second tooth. Eventually, the students completed the
      questionnaire by answering questions that directly compared the two digital
      systems. The gutta-percha filled tooth was measured using the system's own
      software. Two measurements of each tooth were performed: total tooth length (TTL)
      and root filling length (RFL). The teeth were dismounted from the plaster blocks
      and the true TTL and RFL was measured with an electronic slide calliper. The
      majority of the students had used the contrast enhancement facility (CCD sensor =
      52%, PSP = 71%) and the zoom facility (65-68%) whilst some had used the density
      enhancement facility (CCD sensor = 39%, PSP = 55%). The students stated that they
      saved more time when they used the CCD sensor than when they used the PSP system
      (P < 0.001), and that it was easier to position the tooth with the PSP plate than
      with the sensor (P < 0.01). The lengths measured on the digital images from both
      digital systems were marginally larger than the true tooth lengths (P < 0.05).
      However, there was no difference between the two digital systems for the TTL/RFL
      ratio (P > 0.05).

PMID- 15469444
TI  - Undergraduate experience of clinical procedures in paediatric dentistry in a UK
      dental school during 1997-2001.
AB  - Abstract The aim of this study was to determine the clinical experience of
      undergraduate students in paediatric dentistry. This was a prospective study in a
      clinic teaching paediatric dentistry to undergraduates within a UK dental school.
      Students who graduated between 1997 and 2001 at King's Dental Institute, London,
      were required to complete a quantitative record of their clinical activity. The
      mean undergraduate intake for the 5-year period was 58. Thirty-six (36) sessions
      each of 2-2 1/2 h duration were available in the course for the clinical
      treatment of children (one half day per week), a total of 81 h. The
      undergraduates assessed and planned treatment for 13.4 patients, 3.6 emergency
      patients and administered 10.4 local analgesics. The mean number of inhalation
      sedation administrations increased (1.5-3.3) per student during the 5-year
      period. The mean number of procedures performed by undergraduates for primary
      teeth was 8.1 restorations in glass ionomer or compomer and 1.9 in amalgam, 1.6
      pulpotomies and 0.2 preformed crowns. The mean number of procedures for permanent
      teeth was 24.5 fissure sealants, 2.6 preventive resin restorations, 1.5 amalgams,
      1.7 composites, 1.4 incisal edge restorations and 0.8 root canal treatments. For
      permanent teeth, the trend was towards an increase in the number of preventive
      resin restorations (1.9-2.8) and composite restorations (1.4-1.9) but a decrease
      in the number of amalgam restorations (2.1-0.9) during the 5-year period.
      Individual students' clinical experience was very variable. Procedures that were
      performed more than 10 times were experienced by every student. A procedure
      performed on average two to four times within a year group would be experienced
      by only 80-90% of the group and less frequently performed procedures would only
      have been experienced by a minority of graduates. A large number of patients
      failed to attend or cancelled appointments representing a loss of 21 h of
      clinical treatment time per student, about 25% of the total time available for
      the treatment of children in the clinical course.

PMID- 15469445
TI  - British Society for Oral and Maxillofacial Pathology, UK: minimum curriculum in
      oral pathology.
AB  - This paper describes a minimum curriculum in oral pathology for undergraduate
      dental education in the United Kingdom prepared by the Teachers Group of The
      British Society of Oral and Maxillofacial Pathology. Curricular development in UK
      dental schools is overseen by the General Dental Council (GDC), the Quality
      Assurance Agency for Higher Education (QAA) and the European Union. These
      organisations define the framework for education and learning outcomes but
      provide little or no detailed guidance on syllabus or curriculum. This
      recommended minimum curriculum has been drawn up by a consensus process involving
      teachers of oral pathology from all 13 UK and one Irish dental schools and is
      cross-referenced to the GDC and QAA published requirements for undergraduate
      dental education.

PMID- 15469448
TI  - Clinical and genetic features of human prion diseases in Catalonia: 1993-2002.
AB  - We describe the clinical and genetic characteristics of the 85 definite or
      probable human prion diseases cases died between January 1993 and December 2002
      in Catalonia (an autonomous community of Spain, 6 million population). Seventy
      three (86%) cases were sporadic Creutzfeld-Jakob diseases (sCJD) (49 definite, 24
      probable), with a median age at onset of 66 years. The clinical presentation was
      dementia in 29 cases, ataxia in 14 and visual symptoms in five. The median
      survival was 3 months. The 14-3-3 assay was positive in 93% cases, 62% presented
      periodic sharp wave complexes (PSWC) in EEG but only 18% the typical signs on
      MRI. Forty-eight sCJD were studied for codon 129 PRNP polymorphism: 69% were
      methionine/methionine (M/M), 14.5% valine/valine (V/V) and 16.5% M/V. Six out of
      seven V/V cases did not present PSWC and in two survival was longer than 20
      months. Eleven cases (13%) were genetic: five familial fatal insomnia and six
      familial CJD (fCJD). Up to four (67%) fCJD lacked family history of disease, two
      presented seizures early at onset and one neurosensorial deafness. The only
      iatrogenic case was related to a dura mater graft. No case of variant CJD was
      registered. The study confirms in our population the consistent pattern reported
      worldwide on human prion diseases. Atypical features were seen more frequently in
      sporadic 129 V/V CJD and fCJD cases.

PMID- 15469449
TI  - Dysferlin mutation analysis in a group of Italian patients with limb-girdle
      muscular dystrophy and Miyoshi myopathy.
AB  - Mutations in the dysferlin gene (DYSF) on chromosome 2p13 cause distinct
      phenotypes of muscular dystrophy: limb-girdle muscular dystrophy type 2B
      (LGMD2B), Miyoshi myopathy (MM), and distal anterior compartment myopathy, which
      are known by the term 'dysferlinopathy'. We performed mutation analyses of DYSF
      in 14 Italian patients from 10 unrelated families with a deficiency of dysferlin
      protein below 20% of the value in normal controls by immunoblotting analysis. We
      identified 11 different mutations, including eight missense and three deletion
      mutations. Nine of them were novel mutations. We also identified a unique 6-bp
      insertion polymorphism within the coding region of DYSF in 15% of Italian
      population, which was not observed in East Asian populations. The correlation
      between clinical phenotype and the gene mutations was unclear, which suggested
      the role of additional genetic and epigenetic factors in modifying clinical
      symptoms.

PMID- 15469450
TI  - New V272A presenilin 1 mutation with very early onset subcortical dementia and
      parkinsonism.
AB  - In this report, we present the clinical and pathological details of a kindred of
      four individuals with a novel missense mutation (V272A) of the presenilin 1 gene
      (PSEN1) that experienced a subcortical dementia. The age of onset of symptoms
      ranged 26-36-year old, with an age at death of 36-46 years. Initial symptom was a
      marked mood disorder, with prominent parkinsonism in one case. The
      neuropsychological study, as well as the neuroimaging and PET in the proband were
      concordant with a subcortical dementia. The cerebral pathology showed in this
      patient, aside from the classical lesions of Alzheimer disease, Lewy bodies in
      cortex and substantia nigra, and widespread subcortical neuritic lesions. This
      clinical pattern and pathology expands the clinical spectrum of familial
      Alzheimer's disease and compel to include mutations of PSEN1 gene in the genetic
      study of subcortical dementia.

PMID- 15469451
TI  - No effect of eletriptan administration during the aura phase of migraine.
AB  - Migraine aura is a warning sign readily recognized by patients. From the onset of
      aura it takes 30-60 min before the headache phase starts. Administration of acute
      medication during aura should provide sufficient time to achieve therapeutic
      plasma levels, counteracting the headache. To test this hypothesis we evaluated
      the efficacy of eletriptan 80 mg taken during aura. Patients met International
      Headache Society diagnostic criteria for migraine with aura, with an attack
      frequency of at least one per month and with aura occurring in > 50% of recent
      attacks. Of 123 patients randomized, 87 (71%) were treated with a double-blind,
      one attack, during the aura phase before headache, dose of either eletriptan 80
      mg (n = 43; 74% female; mean age, 40 years), or placebo (n = 44; 82% female; mean
      age, 40 years). The primary outcome measure was the proportion of patients not
      developing moderate-to-severe headache within 6 h post-dose. There was no
      significant difference in the proportion of patients developing moderate-to
      severe headache on eletriptan (61%) versus placebo (46%). Eletriptan was well
      tolerated and did not prolong the aura phase. Typical transient triptan adverse
      events were observed; most were mild-to-moderate in intensity. This study
      confirms the findings of two studies showing that triptans are ineffective but
      safe when given during the migraine aura phrase.

PMID- 15469452
TI  - Inadequate management of cerebrovascular risk factors in participants of a public
      stroke prevention program in Austria.
AB  - The aim of our investigation was to identify frequencies and treatment quality of
      stroke risk factors in participants of a stroke prevention program in the
      province of Salzburg (Austria). A total of 9356 participants free of previous
      stroke were classified in three risk categories for suffering from ischemic
      stroke within the next 10 years and analyzed referring to history, therapy, and
      treatment quality of cerebrovascular risk factors. A total of 6519 (69.7%)
      participants were classified to be at low (<10%), 2232 (23.9%) at intermediate
      (10-20%) and 605 (6.5%) at high risk (>20%). Elevated blood pressure with the
      need for follow-up investigations was found in 5193 persons (55.5%); of 3713
      (39.7%) persons with a history of hypertension, 3204 (86.3%) are under medical
      treatment, which is sufficient only in 765 patients (23.9%). Similar results were
      present for other well documented modifiable risk factors. In the investigated
      population there is high presence of stroke risk factors with inadequate
      treatment in most cases.

PMID- 15469453
TI  - Differences between hypertensive and non-hypertensive ischemic stroke.
AB  - We compared risk factors, clinical features, neuroimaging data, and outcome
      between hypertensive and non-hypertensive ischemic stroke patients. Differential
      features of ischemic stroke patients with hypertension (n = 768) and without
      hypertension (n = 705) were assessed by bivariate analysis. Independent
      predictors of hypertensive ischemic stroke were determined by multivariate
      analysis. Atherothrombotic infarction and lacunar infarct were significantly more
      common in the hypertensive group, in which older age and a higher occurrence of
      previous cerebral infarction, hyperlipidemia, acute stroke onset, lacunar
      syndrome, and pons topography was also observed. Age of 85 years or older,
      valvular heart disease, and decreased consciousness were more common in non
      hypertensive patients. After multivariate analysis, lacunar syndrome, female
      gender, and previous infarction were directly associated with hypertensive
      ischemic stroke. Age of 85 years or older and valvular heart disease were
      inversely associated with hypertensive ischemic stroke. Hypertension was the main
      cardiovascular risk factor only for lacunes and atherothrombotic infarction, that
      is, ischemic stroke associated with small- and large-artery disease.

PMID- 15469454
TI  - Refractory status epilepticus due to acute hepatic porphyria in a pregnant woman:
      induced abortion as the sole therapeutic option?
AB  - A 22-years old, 55 kg female patient in the twelfth week of pregnancy developed
      neuropsychiatric syndromes and in the following status epilepticus. Raised
      porphyrines and porphyrine precursors were found in the patient's urine. Despite
      intravenous glucose infusions and appropriate medication no reduction in seizure
      frequency and neuropsychiatric syndromes was observed. An abortion was induced.
      After the interruption and starting of haem arginate therapy, seizure activity
      stopped and porphyrine precursors returned to normal levels, and after 6 weeks
      the patient was discharged in excellent clinical condition. This report describes
      a status epilepticus caused by acute hepatic porphyria, triggered by pregnancy,
      in a 22-years old woman. To our knowledge this is the first report of induced
      abortion as successful treatment in acute hepatic porphyria induced status
      epilepticus.

PMID- 15469455
TI  - Delirium in acute stroke: a preliminary study of the role of anticholinergic
      medications.
AB  - The pathogenesis of delirium in acute stroke is incompletely understood. The use
      of medications with anticholinergic (ACH) activity is associated with an
      increased frequency of delirium. We hypothesized that the intake of medications
      with ACH activity is associated with delirium in acute stroke patients. Delirium
      was assessed using the DSM-IV-TR criteria and the Delirium Rating Scale, in a
      sample of consecutive patients with an acute (< or =4 days) cerebral infarct or
      intracerebral haemorrhage (ICH). We performed a gender and age matched case
      control study. Twenty-two delirious stroke patients (cases) and 52 non-delirious
      patients (controls) were compared concerning the intake of ACH medications (i)
      before stroke, (ii) during hospitalization but before the assessment. The
      variables associated with delirium on bivariate analysis were entered in a
      stepwise logistic regression analysis. The final regression model (Nagelkerke R2
      = 0.65) retained non-neuroleptics ACH medication during hospitalization (OR =
      24.4; 95% CI = 2.18-250), medical complications (OR = 20.8; 95% CI = 3.46-125),
      ACH medication taken before stroke (OR = 17.5; 95% CI = 1.00-333.3) and ICH (OR =
      16.9; 95% CI = 2.73-100) as independent predictors of delirium. This preliminary
      result indicates that drugs with subtle ACH activity play a role in the
      pathogeneses of delirium in acute stroke. Medication with ACH activity should be
      avoided in acute stroke patients.

PMID- 15469456
TI  - Reduced cerebellar vermis activation during urinary storage and micturition in
      multiple system atrophy: 99mTc-labelled ECD SPECT study.
AB  - Single-photon emission computed tomography brain imaging with special reference
      of bladder function was performed in eight multiple system atrophy (MSA) patients
      (two men, six women; mean age, 61 years) and age-matched five normal control
      subjects (three men, two women; 62 years). In both groups imagings were obtained
      in three conditions; empty bladder, storage, and micturition. [99mTc]-labelled
      ECD (555 MBq) was intravenously injected, which was immediately trapped and
      stabilized within the brain. Using NEUROSTAT software, which could also cancel
      morphologic differences between MSA and canonical brain, statistical difference
      between normalized mean tracer counts of both groups in each phase was calculated
      and visualized. In the storage phase, there was a significant decrease in tracer
      activity in bilateral cerebellar vermis, particularly of the right side in the
      MSA group (P < 0.05), which is also known to be involved in the neural control of
      micturition. In the micturition phase, the area of decrease in tracer activity in
      the cerebellar vermis became wider in the MSA group. In the resting state, no
      statistically significance was seen between both groups. In conclusion, it is
      suggested that the decrease in tracer activity in the cerebellar vermis during
      urinary storage and micturition is contributing to the micturitional disturbance
      in this disorder.

PMID- 15469457
TI  - Thiethylperazine-induced parkinsonism: in vivo demonstration of dopamine D2
      receptors blockade.
AB  - Thiethylperazine (Torecan) is a piperazine phenothiazine employed to relieve
      vertigo. Its use may be associated with extrapyramidal side effects (dystonia,
      akathisia, tardive dyskinesia) (Sulkava, 1984), but parkinsonism has rarely been
      described. We describe a woman who, 1 month after the onset of thiethylperazine
      treatment, developed parkinsonism that disappeared 2 months after withdrawal of
      the drug. However, cerebral single-photon emission computed tomography (SPECT)
      with the dopamine (DA) D2 receptors ligand 123I-iodobenzamide (123I-IBZM)
      revealed a persistent reduced DA D2 receptors activity (by 45%) in the basal
      ganglia (BG), which may be clinically not effective.

PMID- 15469458
TI  - Progressive dementia caused by Hashimoto's encephalopathy -- report of two cases.
AB  - Dementia induced by Hashimoto's encephalopathy (HE) seems to be a rare condition.
      We report on two patients, who revealed a syndrome consisting of a rapid
      progressive dementia with myocloni. In both patients, the detection of
      antithyroid antibodies enabled the diagnosis of HE. The symptoms receded
      completely during a high-dose glucocorticoid therapy. In patients with rapidly
      progressive dementia or with dementia of unknown origin, HE should be considered.

PMID- 15469459
TI  - Striatal lesions: an underestimated complication of cerebral malaria?

PMID- 15469460
TI  - The coexistence of familial Mediterranean fever with multiple sclerosis.

PMID- 15469470
TI  - Is there a case for routine clinical application of ploidy measurements in
      gastrointestinal tumours?

PMID- 15469471
TI  - CD10 immunostaining of bile canaliculi in liver biopsies: change of staining
      pattern with the development of cirrhosis.
AB  - AIMS: This study was prompted by published observations concerning the absence of
      normal bile canalicular CD10 staining in some cases of primary liver cell
      carcinoma. Our aim was to investigate the possibility that this loss of staining
      occurs prior to the development of cancer. METHODS AND RESULTS: The study
      comprised 164 liver biopsies, including 96 from patients with hepatitis C
      infection of various grades and stages including nine cases with cirrhosis, 24
      other cases of cirrhosis of other aetiology, five cases of primary liver
      carcinoma, 12 cases of metastatic carcinoma, as well as biopsies with a variety
      of other liver diseases. CD10 was demonstrated in paraffin sections using the
      avidin-biotin immunoperoxidase technique. In hepatitis C cases, a significant
      loss of the canalicular pattern was seen in four out of 41 (10%) biopsies with
      stages 0-1 compared with 25 out of 55 (45%) with stages 2-6 (P < 0.001). There
      was also a significant difference (P < 0.001) between biopsies with stage 2-3 and
      those with stage 4-6, where marked pattern loss was seen in 9/37 (24%) and 16/18
      (89%), respectively. Marked loss of the pattern was also seen in 16 out of the 24
      (67%) other cirrhotic biopsies, as well as in cases with severe lobular
      inflammation and cholestasis and liver cell dysplasia and carcinoma. In hepatitis
      C biopsies, no relationship was noted between the reduction in the canalicular
      pattern and the necroinflammatory score. CONCLUSIONS: CD10-stained bile
      canalicular pattern in liver biopsies is preserved in cases with mild fibrosis
      and inflammation, but it becomes increasingly reduced with the advance of
      fibrosis or the presence of severe lobular inflammation or extensive metastases.
      Further investigations into the relationship between the changes in CD10 staining
      pattern and liver function tests may be useful in explaining test results.

PMID- 15469472
TI  - Ductal carcinoma in situ with spindle cells: a potential diagnostic pitfall in
      the evaluation of breast lesions.
AB  - AIMS: To evaluate the morphological features of 11 cases of breast ductal
      carcinoma in situ (DCIS) with spindle cells and to propose an approach to
      distinguish it from benign mimics. The association with neuroendocrine
      differentiation was also investigated. METHODS: Cases of breast DCIS with a
      spindle cell component diagnosed in the Department of Pathology, Singapore
      General Hospital, between June 1996 and January 2003, were included in the study.
      The histological characteristics were documented, and immunohistochemistry for
      neuroendocrine markers, hormone receptors, cerbB2, smooth muscle actin (SMA) and
      high-molecular-weight (HMW) cytokeratins, was carried out. Electron microscopy
      was carried out on reprocessed paraffin-embedded material in three cases.
      RESULTS: Of 11 women diagnosed with DCIS with spindle cells, four presented with
      nipple discharge, six with a breast lump, while one was discovered to have a
      screen detected density. The tumour size ranged from 3 to 41 mm. The proportion
      of spindle cells varied from 10% to 80% of the in-situ tumour cell population.
      Nuclear grade was low in seven cases and intermediate in four. Necrosis was
      observed in two cases. Architectural pattern was papillary in six cases, and
      mixed in the rest. Microinvasion was present in two cases, with possible
      microinvasion in another two. Immunohistochemistry for neuroendocrine markers
      synaptophysin and chromogranin showed positive reactivity for at least one marker
      in all but three cases; one of these latter cases demonstrated ultrastructural
      neurosecretory granules. Oestrogen and progesterone receptors were expressed in
      10 and nine cases, respectively, while cerbB2 was positive in only one case. HMW
      cytokeratin immunoprofile revealed a general lack of immunostaining within the
      abnormal cell population; likewise, no positivity for SMA of the cellular
      proliferation was detected. CONCLUSIONS: Almost all DCIS lesions with spindle
      cells disclose neuroendocrine differentiation. Although the distinction from
      benign florid usual hyperplasia may pose a diagnostic histological problem, the
      presence of diffuse neuroendocrine expression, in conjunction with the pattern of
      HMW keratin profile on immunohistochemistry, supports an in-situ neoplastic
      process. The absence of SMA immunostaining, in conjunction with negative
      reactivity for cytokeratins 5/6 and 14, makes the possibility of a myoepithelial
      proliferation unlikely.

PMID- 15469473
TI  - The role of nuclear morphometry in prediction of prognosis for rhabdomyosarcoma
      in children.
AB  - AIMS: To determine whether nuclear morphometry can be used in pretreatment
      diagnostic procedures to guide the therapy of childhood rhabdomyosarcoma (RMS).
      MATERIALS AND METHODS: Biopsy specimens obtained from 108 patients with
      rhabdomyosarcoma aged between 1 and 217 months treated in 12 paediatric oncology
      departments in Poland were evaluated. There were 65 (60.2%) specimens of
      embryonal rhabdomyosarcoma (RME), 32 (29.6%) of alveolar RMS (RMA) and 11 (10.2%)
      cases of undifferentiated RMS (RMU). The clinical data from all analysed patients
      were evaluated. Nuclear morphometry was performed semiautomatically on
      haematoxylin-eosin-stained sections using the MultiScan v.8.08 Computer Scanning
      System and an Olympus BX 50 microscope with a x 40 magnification lens. RESULTS:
      In the RMA subtype cells with spindle-shape nuclei were less common (P = 0.013)
      and cell nuclei were generally more round in comparison with RME (P = 0.033). The
      clinical outcome was better if the nuclei seen in biopsies of RMS were more
      spindle-shaped (event-free survival 0.51 and 0.23, respectively; P = 0.04) or
      more cells with spindle-shaped nuclei were observed (event-free survival 0.5 and
      0.28, P = 0.035). RME patients with small nuclei had a better outcome then
      patients with large nuclei (P = 0.014). In the RMA/RMU group, patients with small
      tumour cell nuclei had a worse prognosis than patients with larg tumour cell
      nuclei (P = 0.046). CONCLUSIONS: Nuclear morphometry is a useful tool in the
      assessment of children with RMS. Additionally, certain morphometric parameters
      could be easily applied in a selection of patients with good prognosis.

PMID- 15469474
TI  - Cellular angiofibroma and related fibromatous lesions of the vulva: report of a
      series of cases with a morphological spectrum wider than previously described.
AB  - AIMS: Cellular angiofibroma (CA) is a rare benign mesenchymal lesion with a
      predilection for the vulval region. In this report we aim to describe the
      clinical, pathological and immunohistochemical features of a series of vulval
      mesenchymal lesions, some of which have the classically described histological
      appearance of CA while others exhibit atypical features. We believe these lesions
      fall within the broad spectrum of fibromatous lesions of the vulva. METHODS AND
      RESULTS: Seven cases were included. Histological sections were examined and
      immunohistochemical staining with vimentin, desmin, alpha smooth muscle actin, h
      caldesmon, S100, EMA, AE1/3, CD34, CD10, ER, PR and MIB1 was performed. The
      patients' ages ranged from 20 to 65 years and the lesions ranged in size from 10
      to 50 mm. All lesions were well circumscribed, moderately cellular lesions and
      were composed of bland spindle-shaped cells set in a fibrous stroma. Many blood
      vessels with thick hyalinized walls were present in four cases, in one case
      occasional such blood vessels were present and in two cases vessels with thick
      hyalinized walls were not present. In five cases the vessels were at least
      focally dilated resulting in a haemangiopericytomatous pattern. Histological
      features identified in a variable numbers of cases included peripheral adipose
      tissue (four cases), adipose tissue within the centre of the lesion (one case),
      stromal mast cells (six cases), stromal lymphoid aggregates (five cases),
      scattered multinucleate cells (five cases), hypocellular hyalinized areas (two
      cases), myxoid areas (four cases) and focal areas of marked cellular atypia
      reminiscent of symplastic change within a uterine leiomyoma (one case). Mitotic
      figures were identified in four cases, all with a mitotic count of < 1 per 10
      high-power fields. Immunohistochemically all neoplasms were positive with
      vimentin and all but one with ER and PR (PR staining was not performed in one
      tumour). In all cases desmin, alpha smooth muscle actin, h-caldesmon, S100 and
      AE1/3 were negative (h-caldesmon and AE1/3 staining were not performed in one
      case). Three cases were positive with CD34, one with EMA and two with CD10. All
      exhibited a low MIB1 proliferation index of approximately 1%. One lesion recurred
      locally 6 months following initial removal. CONCLUSIONS: CA is a rare benign
      vulval mesenchymal lesion with limited potential for local recurrence. We
      describe several hitherto unreported histological features which add to the
      morphological spectrum. Although not all lesions exhibit the classically
      described histological features of CA, we believe all fall within the broad
      spectrum of benign vulval fibromatous lesions. These cases are characterized by
      vimentin positivity but negative staining with smooth muscle markers which
      assists in excluding many of the other vulvovaginal mesenchymal lesions which
      enter into the differential diagnosis. The immunophenotype indicates that CA
      probably exhibits fibroblastic rather than myofibroblastic differentiation. These
      lesions are almost always positive with ER and PR, suggesting that they probably
      arise from the hormone receptor-positive subepithelial mesenchymal layer within
      the lower female genital tract.

PMID- 15469475
TI  - Liposclerosing myxofibrous tumour: a traumatized variant of fibrous dysplasia?
      Report of four cases and review of the literature.
AB  - AIMS: To describe the pathological and radiological features of four cases of
      liposclerosing myxofibrous tumour (LSMFT). LSMFT is a benign fibro-osseous lesion
      of bone with a marked predilection for the intertrochanteric region of the
      proximal femur. It is characterized by a complex mixture of histological elements
      including fibrous dysplasia-like bony trabeculae, myxofibrous tissue, lipomatous
      areas, xanthoma cells and pseudo-Paget's bone. This lesion is not a universally
      accepted pathological entity and often appears in the literature under variants
      of fibrous dysplasia or other benign lytic bone lesions. METHODS AND RESULTS: All
      lesions exhibited histological and/or radiological overlap with fibrous
      dysplasia. A relationship to trauma was noted in three of the cases. The
      hypothesis that these lesions represent a traumatized variant of fibrous
      dysplasia was explored. After reviewing the biomechanics of the proximal femur, a
      possible relationship between predilection of LSFMT for this anatomical region
      and increased susceptibility to fracture was noted. CONCLUSIONS: We hypothesize
      that when fibrous dysplasia involves the proximal femur, it makes the bone more
      susceptible to fatigue fracture, thereby altering its histological appearance.
      The wide variety of histological patterns in LSMFT could represent the end result
      of repeated reaction to fatigue stresses.

PMID- 15469476
TI  - Neutrophilic phlebitis is characteristic of intestinal Behcet's disease and
      simple ulcer syndrome.
AB  - AIM: To characterize the histological features of intestinal Behcet's disease and
      simple ulcer syndrome and to clarify the possible mechanisms involved in their
      development by analysing the type of inflammatory infiltrates in the diseased
      intestine and the expression of adhesion molecules on endothelial cells. METHODS
      AND RESULTS: Tissue samples from 10 patients diagnosed as having intestinal
      Behcet's disease or simple ulcer syndrome were studied. Immunohistochemical
      studies were performed on paraffin-embedded tissue using a labelled streptavidin
      biotin method. In all cases, phlebitis was remarkably seen in submucosal
      inflammatory lesions, but the adjacent arteries were not affected. Inflammatory
      infiltrates around the affected vessels consisted of neutrophils and mononuclear
      cells, and neutrophils predominated over CD68+ macrophages and lymphocytes. The
      majority of mononuclear cells were CD3+ T cells, and CD4+ cells were more
      frequent than CD8+ T cells. As for adhesion molecule expression, intercellular
      adhesion molecule-1, but not vascular cell adhesion molecule-1, was expressed in
      most endothelial cells of the vessels with phlebitis, some of which were also
      positive for HLA-DR. CONCLUSION: Neutrophilic phlebitis may be involved in the
      pathogenesis of intestinal Behcet's disease and simple ulcer syndrome.

PMID- 15469477
TI  - Prevalence of CD99 protein expression in pancreatic endocrine tumours (PETs).
AB  - AIMS: To determine the prevalence of CD99 expression in pancreatic endocrine
      tumours (PETs). We evaluated CD99 expression and analysed Ki67 labelling by
      immunohistochemistry in PETs. METHODS AND RESULTS: Thirty-eight PETs from 33
      patients were analysed. CD99 immunoreactivity was consistently observed in normal
      islets of the pancreas, regardless of the cell type. Tumours comprising more than
      30% CD99+ cells were defined as positively immunoreactive for CD99. CD99
      expression was observed in 20 of the 38 PETs examined, but not in any of the
      pancreatic tumours of other histological subtypes (10 ductal adenocarcinomas,
      five intraductal papillary-mucinous tumours, and two acinar cell tumours). Loss
      of CD99 expression was related to markers of worse prognosis for PET, including
      gross local invasion, metastasis to the lymph nodes or other organs, lymphatic or
      blood vessel invasion, and neuroendocrine carcinoma (NEC). Thus, CD99 expression
      may have an efficiency comparable to that of high Ki67 labelling index (5% or
      more) for prognostication. CONCLUSIONS: CD99 expression was observed frequently
      and exclusively in PETs, and loss of CD99 expression in PETs was found to be
      associated with ominous prognostic indicators.

PMID- 15469478
TI  - The pathology associated with therapeutic procedures in malignant mesothelioma.
AB  - AIMS: To describe iatrogenic pathological lesions in malignant pleural
      mesothelioma. METHODS AND RESULTS: All cases of malignant pleural mesothelioma
      confirmed by antemortem pleural biopsy and undergoing post mortem examination
      over a 7-year period (1995-2001) formed the study group. This comprised 48
      malignant pleural mesotheliomas [epithelioid (n = 21), biphasic (n = 14) and
      sarcomatoid (n = 13)]. Twenty-eight of 48 (58%) had received chemical (talc)
      pleurodesis, 30/48 (63%) palliative localized radiotherapy, 6/48 (13%)
      chemotherapy, and 14/48 (30%) surgery [12/48 (26%) pleural decortication and 2/48
      (4%) pleuropneumonectomy]. CONCLUSIONS: Talc pleurodesis induces a marked
      pseudosarcomatous fibroblastic proliferation which may impart a biphasic pattern
      to the neoplasm. In more chronic cases, paucicellular fibrosis with a foreign
      body giant cell reaction is noted. The talc is polarizable and deposited in
      linear fashion within the tumour. In 2/28 (7%) pleurodesis cases platyform
      ferruginous bodies were seen in the peripheral alveolated lung parenchyma and
      these mimicked asbestos bodies. An awareness of this is important to prevent
      false attribution to asbestos. Talc could be identified by transmission electron
      microscopic mineral analysis in 5/15 (33%) cases examined. Tumour nodules
      developing subjacent to iatrogenic wound sites were noted in 8/48 (17%) cases. In
      6/8 (75%) of these cases, comparative assessment of the locally irradiated
      subcutaneous chest wall tumour, with background pleural mesothelioma, showed no
      morphological difference in architectural tumour growth pattern, extent of
      necrosis, cytological or nuclear pleomorphism, mitotic activity or tumour
      immunophenotype. In 2/8 (25%) cases the locally irradiated tumour showed
      prominent bizarre multinucleated tumour giant cells and intense mixed
      inflammation, a feature not seen in the background (non-irradiated) tumour. All
      six malignant pleural mesotheliomas receiving chemotherapy appeared refractory to
      treatment in that chemotherapy did not appear to have any significant effect on
      the tumour morphology, cytonuclear pleomorphism, mitotic activity, extent of
      necrosis or immunophenotype. In the 12 decortication specimens and two
      pleuropneumonectomy resections, post mortem examination identified evidence of
      residual malignant mesothelioma of similar morphological subtype and
      immunophenotype to the resected tumour.

PMID- 15469479
TI  - Rare expression of KIT (CD117) in lymphomas: a tissue microarray study of 1166
      cases.
AB  - AIMS: Imatinib mesylate specifically inhibits KIT tyrosine kinase activity, and
      has been proven to be effective in the treatment of gastrointestinal stromal
      tumours. Because other KIT-expressing malignancies might benefit from Imatinib
      therapy, we evaluated the distribution and expression of KIT in 1166 cases of
      malignant lymphoma. MATERIALS AND RESULTS: Tissue microarrays (TMAs) containing
      824 non-Hodgkin's lymphoma (NHL) and 342 Hodgkin's lymphoma (HL) cases were
      immunohistochemically analysed for the expression of the KIT protein. Two KIT
      positive NHLs were sequenced using polymerase chain reaction analysis. One T-cell
      lymphoma and one follicular lymphoma of the 747 NHL cases (0.3%) were positive
      for KIT. All HLs were Kit-negative. None of the KIT-positive cases showed a kit
      gene mutation. CONCLUSIONS: KIT expression is a very rare event in NHL and
      virtually absent in HL. In the few positive cases, the aberrant expression is not
      caused by a mutation in the 'hot-spots' of the kit gene, indicating that
      treatment of these tumours with Imatinib may be ineffective.

PMID- 15469480
TI  - Tenascin-C in primary malignant melanoma of the skin.
AB  - AIMS: To investigate the expression and the prognostic role of glycoprotein
      Tenascin-C (Tn-C) in primary melanoma of the skin. METHODS AND RESULTS: The
      immunohistochemical expression of Tn-C was studied in 98 primary melanomas and
      related to inflammation, invasion, and patient outcome. Patients were followed up
      for disease recurrence for 0.04-7.4 years (median 3.9) and for survival for 0.5
      to 12.1 years (median 9.3). The expression of Tn-C was evaluated for each tumour
      invasion border; the stromal and intracytoplasmic Tn-C of the melanoma islets
      were also recorded. Tn-C is widely expressed in primary melanoma samples, the
      staining pattern varying from focal to diffuse in different parts of the tumour.
      No correlation existed between intensity of Tn-C staining and inflammation. No
      stromal Tn-C was detected at the upper dermal lateral border in 12 patients, nor
      at the deep, dermal or subcutaneous border in 14 patients. These patients showed
      better disease-free survival (DFS) than did those cases with focal or diffuse
      staining (P = 0.06, P = 0.05). Also, absence of intracytoplasmic Tn-C was a
      beneficial prognostic factor for DFS (P = 0.04). In multivariate analysis, tumour
      ulceration and intracytoplasmic Tn-C expression of melanoma cells were
      independent adverse prognostic factors for DFS. CONCLUSIONS: In primary melanoma
      of the skin, absence of Tn-C in the stroma of invasion fronts and within tumour
      cells seems to be related to a more benign disease behaviour with a lower risk of
      developing metastases.

PMID- 15469481
TI  - Transplant histopathology of the general histopathologist.

PMID- 15469482
TI  - Apocrine sclerosing adenosis of the sweat glands.

PMID- 15469483
TI  - Reducing the workload of a histopathology department.

PMID- 15469484
TI  - Paget's disease of the nipple occurring after conservative surgery for ductal
      carcinoma in situ of the breast.

PMID- 15469485
TI  - Hepatic inflammatory pseudotumour related to autoimmune pancreatitis.

PMID- 15469486
TI  - Morphological and immunohistochemical characterization of an endometriotic cyst
      of the liver: diagnostic approach to endometriosis.

PMID- 15469487
TI  - Basal cell (myoepithelial) adenocarcinoma of the lung. First case with
      cytogenetic findings.

PMID- 15469488
TI  - Spindle cell variant of papillary thyroid carcinoma.

PMID- 15469489
TI  - Diffuse embryoma with intratubular germ-cell neoplasia.

PMID- 15469491
TI  - Disruption and overexpression of auxin response factor 8 gene of Arabidopsis
      affect hypocotyl elongation and root growth habit, indicating its possible
      involvement in auxin homeostasis in light condition.
AB  - Auxin response factor (ARF) family genes play a central role in controlling
      sensitivity to the plant hormone auxin. We characterized the function of ARF8 in
      Arabidopsis by investigating a T-DNA insertion line (arf8-1) and overexpression
      lines (ARF8 OX) of ARF8. arf8-1 showed a long-hypocotyl phenotype in either
      white, blue, red or far-red light conditions, in contrast to ARF8 OX that
      displayed short hypocotyls in the light. Stronger and weaker apical dominance,
      and promotion and inhibition of lateral root formation were observed in arf8-1
      and ARF8 OX respectively. Sensitivity to auxin was unaltered in arf8-1 hypocotyls
      with respect to growth inhibition caused by exogenously applied auxin and growth
      promotion induced by higher temperatures. ARF8 expression was observed
      constitutively in shoot and root apexes, and was induced in the light condition
      in hypocotyls. Free IAA contents were approximately 30% reduced in light-grown
      hypocotyls of ARF8 OX, but were similar between those of arf8-1 and wild type.
      Expression of the three GH3 genes was reduced in arf8-1 and increased in ARF8 OX,
      indicating that they are targets of ARF8 transcriptional control. Because the
      three GH3 proteins may be involved in the conjugation of IAA as suggested by
      Staswick et al. (2002), and because two of the three GH3 genes are auxin
      inducible, ARF8 may control the free IAA level in a negative feedback fashion by
      regulating GH3 gene expression. ARF family genes seem to control both auxin
      sensitivity and homeostasis in Arabidopsis.

PMID- 15469492
TI  - Manipulation of DET1 expression in tomato results in photomorphogenic phenotypes
      caused by post-transcriptional gene silencing.
AB  - The tomato HIGH PIGMENT-2 gene encodes an orthologue of the Arabidopsis nuclear
      protein DE-ETIOLATED 1 (DET1). From genetic analyses it has been proposed that
      DET1 is a negative regulator of light signal transduction, and recent results
      indicate that it may control light-regulated gene expression at the level of
      chromatin remodelling. To gain further understanding about the function of DET1
      during plant development, we generated a range of overexpression constructs and
      introduced them into tomato. Unexpectedly, we only observed phenotypes
      characteristic of DET1 inactivation, i.e. hyper-responsiveness to light.
      Molecular analysis indicated in all cases that these phenotypes were a result of
      suppression of endogenous DET1 expression, due to post-transcriptional gene
      silencing. DET1 silencing was often lethal when it occurred at relatively early
      stages of plant development, whereas light hyper-responsive phenotypes were
      obtained when silencing occurred later on. The appearance of phenotypes
      correlated with the generation of siRNAs but not DNA hypermethylation, and was
      most efficient when using constructs with mutations in the DET1 coding sequence
      or with constructs containing only the 3'-terminal portion of the gene. These
      results indicate an important function for DET1 throughout plant development and
      demonstrate that silencing of DET1 in fruits results in increased carotenoids,
      which may have biotechnological potential.

PMID- 15469493
TI  - The nuclear localization signal and the C-terminal region of FHY1 are required
      for transmission of phytochrome A signals.
AB  - Plants use the family of phytochrome photoreceptors to sense their light
      environment in the red/far-red region of the spectrum. Phytochrome A (phyA) is
      the primary photoreceptor that regulates germination and early seedling
      development. This phytochrome mediates seedling de-etiolation for the
      developmental transition from heterotrophic to photoauxotrophic growth. High
      intensity far-red light provides a way to specifically assess the role of phyA in
      this process and was used to isolate phyA-signaling intermediates. fhy1 and pat3
      (renamed fhy1-3) are independently isolated alleles of a gene encoding a phyA
      signal transduction component. FHY1 is a small 24 kDa protein that shows no
      homology to known functional motifs, besides a small conserved septin-related
      domain at the C-terminus, a putative nuclear localization signal (NLS) and a
      putative nuclear exclusion signal (NES). Here we demonstrate that the septin
      related domain is important for FHY1 to transmit phyA signals. Moreover, the
      putative NLS and NES of FHY1 are indeed involved in its nuclear localization and
      exclusion. Nuclear localization of FHY1 is needed for it to execute responses
      downstream of phyA. Together with the results from global expression analysis,
      our findings point to an important role of FHY1 in phyA signaling through its
      nuclear translocation and induction of gene expression.

PMID- 15469494
TI  - Two Arabidopsis srfr (suppressor of rps4-RLD) mutants exhibit avrRps4-specific
      disease resistance independent of RPS4.
AB  - RPS4 specifies the Arabidopsis disease resistance response to Pseudomonas
      syringae pv. tomato expressing avrRps4 and was cloned based on the identification
      of RLD as a naturally occurring susceptible accession. To dissect the molecular
      and genetic basis of disease resistance, we used a genetic approach to identify
      suppressor mutations that reactivate the avrRps4-triggered defense response in
      RLD. In this report, we describe two non-allelic srfr (suppressor of rps4-RLD)
      mutants, srfr1 and srfr3, that were susceptible to virulent P. syringae pv.
      tomato strain DC3000, but resistant to DC3000 expressing avrRps4. In quantitative
      bacterial growth assays, growth of DC3000 was similar in wild-type control and
      both mutant lines, indicating that basal resistance was not enhanced in srfr1 and
      srfr3. Growth of DC3000 (avrRps4) was approximately 30-fold lower in srfr1 and
      srfr3 than in RLD, but intermediate compared with fully resistant Col-0 and
      transgenic RLD containing RPS4-Col. The srfr1 and srfr3 mutants did not develop
      spontaneous lesions prior to inoculation or constitutively express the
      pathogenesis-related gene PR-1. Therefore, srfr1 and srfr3 constitute novel avr
      specific mutants that differ from previously described Arabidopsis mutants with
      elevated disease resistance. The srfr1 and srfr3 mutations were recessive, and
      both mapped to the bottom of chromosome IV. Genetic analysis indicated that
      resistance in srfr1 and srfr3 was independent of the rps4-RLD allele, but
      dependent on a second gene in RLD. We propose that SRFR1 and SRFR3 are negative
      regulators of avrRps4-triggered gene-for-gene disease resistance.

PMID- 15469495
TI  - The potyvirus recessive resistance gene, sbm1, identifies a novel role for
      translation initiation factor eIF4E in cell-to-cell trafficking.
AB  - From the characterization of the recessive resistance gene, sbm1, in pea we have
      identified the eukaryotic translation initiation factor, eIF4E, as a
      susceptibility factor required for infection with the Potyvirus, Pea seed-borne
      mosaic virus. A functional analysis of the mode of action of the product of the
      dominant allele revealed a novel function for eIF4E in its support for virus
      movement from cell-to-cell, in addition to its probable support for viral RNA
      translation, and hence replication. Different resistance specificities in two
      independent pea lines were explained by different mutations in eIF4E. On the
      modelled structure of eIF4E the coding changes were in both cases lying in and
      around the structural pocket involved in binding the 5'-m7G cap of eukaryotic
      mRNAs. Protein expression and cap-binding analysis showed that eIF4E encoded by a
      resistant plant could not bind to m7G-Sepharose, a result which may point to
      functional redundancy between eIF4E and the paralogous eIF(iso)4E in resistant
      peas. These observations, together with related findings for other potyvirus
      recessive resistances, provide a more complete picture of the potyvirus life
      cycle.

PMID- 15469496
TI  - Molecular dissection of plant cytokinesis and phragmoplast structure: a survey of
      GFP-tagged proteins.
AB  - To identify molecular players implicated in cytokinesis and division plane
      determination, the Arabidopsis thaliana genome was explored for potential
      cytokinesis genes. More than 100 open reading frames were selected based on
      similarity to yeast and animal cytokinesis genes, cytoskeleton and polarity
      genes, and Nicotiana tabacum genes showing cell cycle-controlled expression. The
      subcellular localization of these proteins was determined by means of GFP tagging
      in tobacco Bright Yellow-2 cells and Arabidopsis plants. Detailed confocal
      microscopy identified 15 proteins targeted to distinct regions of the
      phragmoplast and the cell plate. EB1- and MAP65-like proteins were associated
      with the plus-end, the minus-end, or along the entire length of microtubules. The
      actin-binding protein myosin, the kinase Aurora, and a novel cell cycle protein
      designated T22, accumulated preferentially at the midline. EB1 and Aurora, in
      addition to other regulatory proteins (homologs of Mob1, Sid1, and Sid2), were
      targeted to the nucleus, suggesting that this organelle operates as a
      coordinating hub for cytokinesis.

PMID- 15469497
TI  - BRL1, a leucine-rich repeat receptor-like protein kinase, is functionally
      redundant with BRI1 in regulating Arabidopsis brassinosteroid signaling.
AB  - BRI1-like receptor kinase (BRL1) was identified as an extragenic suppressor of a
      weak bri1 allele, bri1-5, in an activation-tagging genetic screen for novel
      brassinosteroid (BR) signal transduction regulators. BRL1 encodes a leucine-rich
      repeat receptor-like protein kinase (LRR-RLK). Sequence alignment revealed that
      BRL1 is closely related to BRI1, which is involved in BR perception.
      Overexpression of a BRL1 cDNA, driven by a constitutive CaMV 35S promoter,
      recapitulates the bri1-5 suppression phenotypes, and partially complements the
      phenotypes of a null bri1 allele, bri1-4. Analysis of a BR-specific feedback
      response gene, CPD, indicates that BRL1 functions in BR signaling. BRL1
      expression pattern overlaps with, but is distinct from, that of BRI1. In
      addition, both the expression level and in vitro kinase autophosphorylation
      activity of BRL1 are significantly lower than those of BRI1. bri1-5 brl1-1 double
      mutant plants have enhanced developmental defects relative to bri1-5 mutant
      plants, revealing that BRL1 plays a partially redundant role with BRI1 in
      controlling Arabidopsis growth and development. These findings enhance our
      understanding of functional redundancy and add an additional layer of complexity
      to RLK-mediated BR signaling transduction in Arabidopsis.

PMID- 15469498
TI  - A novel C-terminal sequence from barley polyamine oxidase is a vacuolar sorting
      signal.
AB  - Barley contains two different isoforms of flavin-containing polyamine oxidase
      (BPAO1 and BPAO2). We have previously demonstrated that BPAO2 is a symplastic
      protein in barley leaves. On the contrary, maize polyamine oxidase (MPAO), the
      best characterized member of this enzyme class, is apoplastic. Comparison of the
      derived amino-acid sequences of BPAO2 and MPAO has revealed that both precursor
      proteins include a cleavable N-terminal signal peptide of 25 amino acid residues,
      but the barley enzyme shows an extra C-terminal extension of eight amino acids.
      By means of MPAO engineering with BPAO2 C-terminal tail (MPAO-T) and exploiting
      transient expression in Nicotiana tabacum protoplasts, we demonstrate that this
      oligopeptide is a signal for protein sorting to the plant vacuole. The vacuolar
      sorting of MPAO-T was saturable. Specific mutations of the C-terminal tail were
      constructed to determine which amino acid residues of this novel propeptide
      affect proper protein sorting. No consensus sequence or common structural
      determinant is required for the intracellular retention of the MPAO-T protein,
      but a gradual lowering of the efficiency was observed as a result of progressive
      deletion of the C-terminus.

PMID- 15469499
TI  - Detection of protein-protein interactions in plants using bimolecular
      fluorescence complementation.
AB  - Protein function is often mediated via formation of stable or transient
      complexes. Here we report the determination of protein-protein interactions in
      plants using bimolecular fluorescence complementation (BiFC). The yellow
      fluorescent protein (YFP) was split into two non-overlapping N-terminal (YN) and
      C-terminal (YC) fragments. Each fragment was cloned in-frame to a gene of
      interest, enabling expression of fusion proteins. To demonstrate the feasibility
      of BiFC in plants, two pairs of interacting proteins were utilized: (i) the alpha
      and beta subunits of the Arabidopsis protein farnesyltransferase (PFT), and (ii)
      the polycomb proteins, FERTILIZATION-INDEPENDENT ENDOSPERM (FIE) and MEDEA (MEA).
      Members of each protein pair were transiently co-expressed in leaf epidermal
      cells of Nicotiana benthamiana or Arabidopsis. Reconstitution of a fluorescing
      YFP chromophore occurred only when the inquest proteins interacted. No
      fluorescence was detected following co-expression of free non-fused YN and YC or
      non-interacting protein pairs. Yellow fluorescence was detected in the cytoplasm
      of cells that expressed PFT alpha and beta subunits, or in nuclei and cytoplasm
      of cells that expressed FIE and MEA. In vivo measurements of fluorescence spectra
      emitted from reconstituted YFPs were identical to that of a non-split YFP,
      confirming reconstitution of the chromophore. Expression of the inquest proteins
      was verified by immunoblot analysis using monoclonal antibodies directed against
      tags within the hybrid proteins. In addition, protein interactions were confirmed
      by immunoprecipitations. These results demonstrate that plant BiFC is a simple,
      reliable and relatively fast method for determining protein-protein interactions
      in plants.

PMID- 15469500
TI  - Visualization of protein interactions in living plant cells using bimolecular
      fluorescence complementation.
AB  - Dynamic networks of protein-protein interactions regulate numerous cellular
      processes and determine the ability to respond appropriately to environmental
      stimuli. However, the investigation of protein complex formation in living plant
      cells by methods such as fluorescence resonance energy transfer has remained
      experimentally difficult, time consuming and requires sophisticated technical
      equipment. Here, we report the implementation of a bimolecular fluorescence
      complementation (BiFC) technique for visualization of protein-protein
      interactions in plant cells. This approach relies on the formation of a
      fluorescent complex by two non-fluorescent fragments of the yellow fluorescent
      protein brought together by association of interacting proteins fused to these
      fragments (Hu et al., 2002). To enable BiFC analyses in plant cells, we generated
      different complementary sets of expression vectors, which enable protein
      interaction studies in transiently or stably transformed cells. These vectors
      were used to investigate and visualize homodimerization of the basic leucine
      zipper (bZIP) transcription factor bZIP63 and the zinc finger protein lesion
      simulating disease 1 (LSD1) from Arabidopsis as well as the dimer formation of
      the tobacco 14-3-3 protein T14-3c. The interaction analyses of these model
      proteins established the feasibility of BiFC analyses for efficient visualization
      of structurally distinct proteins in different cellular compartments. Our
      investigations revealed a remarkable signal fluorescence intensity of interacting
      protein complexes as well as a high reproducibility and technical simplicity of
      the method in different plant systems. Consequently, the BiFC approach should
      significantly facilitate the visualization of the subcellular sites of protein
      interactions under conditions that closely reflect the normal physiological
      environment.

PMID- 15469501
TI  - The upstream oxylipin profile of Arabidopsis thaliana: a tool to scan for
      oxidative stresses.
AB  - Various physiological imbalances lead to reactive oxygen species (ROS)
      overproduction and/or increases in lipoxygenase (LOX) activities, both events
      ending in lipid peroxidation of polyunsaturated fatty acids (PUFAs). Besides the
      quantification of such a process, the development of tools is necessary in order
      to allow the identification of the primary cause of its development and
      localization. A biochemical method assessing 9 LOX, 13 LOX and ROS-mediated
      peroxidation of membrane-bound and free PUFAs has been improved. The assay is
      based on the analysis of hydroxy fatty acids derived from PUFA hydroperoxides by
      both the straight and chiral phase high-performance liquid chromatography.
      Besides the upstream products of peroxidation of the 18:2 and 18:3 PUFAs,
      products coming from the 16:3 were characterized and their steady-state level
      quantified. Moreover, the observation that the relative amounts of the ROS
      mediated peroxidation isomers of 18:3 were constant in leaves allowed us to
      circumvent the chiral analyses for the discrimination and quantification of 9
      LOX, 13 LOX and ROS-mediated processes in routine experiments. The methodology
      has been successfully applied to decipher lipid peroxidation in Arabidopsis
      leaves submitted to biotic and abiotic stresses. We provide evidence of the
      relative timing of enzymatic and non-enzymatic lipid peroxidation processes. The
      13 LOX pathway is activated early whatever the nature of the stress, leading to
      the peroxidation of chloroplast lipids. Under cadmium stress, the 9 LOX pathway
      added to the 13 LOX one. ROS-mediated peroxidation was mainly driven by light and
      always appeared as a late process.

PMID- 15469502
TI  - Modulation of AraC family member activity by protein ligands.
AB  - A number of AraC family transcriptional activators bind low-molecular-weight
      ligands that modulate the activity of these proteins. Recently, it has become
      clear that the activity of several virulence-related AraC family members is
      regulated through the direct interaction of protein ligands. These interactions,
      in general, function to activate or repress the transcription of virulence genes
      in response to specific extracellular stimuli. The identification and
      characterization of several protein ligands that modify the activity of AraC
      family members in Pseudomonas aeruginosa and Salmonella enterica are discussed
      herein.

PMID- 15469503
TI  - Calcium signalling in bacteria.
AB  - Whereas the importance of calcium as a cell regulator is well established in
      eukaryotes, the role of calcium in prokaryotes is still elusive. Over the past
      few years, there has been an increased interest in the role of calcium in
      bacteria. It has been demonstrated that as in eukaryotic organisms, the
      intracellular calcium concentration in prokaryotes is tightly regulated ranging
      from 100 to 300 nM. It has been found that calcium ions are involved in the
      maintenance of cell structure, motility, transport and cell differentiation
      processes such as sporulation, heterocyst formation and fruiting body
      development. In addition, a number of calcium-binding proteins have been isolated
      in several prokaryotic organisms. The characterization of these proteins and the
      identification of other factors suggest the possibility that calcium signal
      transduction exists in bacteria. This review presents recent developments of
      calcium in bacteria as it relates to signal transduction.

PMID- 15469504
TI  - The elusive malaria sporozoite in the mammalian host.
AB  - Malaria infection is initiated when Plasmodium sporozoites are injected into a
      host during the bite of an infected mosquito. In the mammal, the sporozoite must
      rapidly reach an intravacuolar niche within a hepatocyte, where it will generate
      the parasite stage that invades red blood cells and causes the symptoms of the
      disease. Herein, we describe our understanding of the way in which sporozoites
      travel from the site of the mosquito bite to the liver, arrest in the liver,
      cross the sinusoidal barrier and eventually gain access to hepatocytes. We also
      highlight some of the recent advances in our understanding of these processes at
      the molecular level.

PMID- 15469505
TI  - An in vivo inducible gene of Pseudomonas aeruginosa encodes an anti-ExsA to
      suppress the type III secretion system.
AB  - We have previously reported on the isolation of in vivo inducible genes of
      Pseudomonas aeruginosa using IVET system. One of such genes isolated from burn
      mouse infection model encodes a short open reading frame with unknown function.
      In this study, we demonstrate that this gene product specifically suppresses the
      expression of type III secretion genes in P. aeruginosa, thus named PtrA
      (Pseudomonas type III repressor A). A direct interaction between the PtrA and
      type III transcriptional activator ExsA was demonstrated, suggesting that its
      repressor function is probably realized through inhibition of the ExsA protein
      function. Indeed, an elevated expression of the exsA compensates the repressor
      effect of the PtrA. Interestingly, expression of the ptrA is highly and
      specifically induced by copper cation. A copper- responsive two-component
      regulatory system, copR-copS, has also been identified and shown to be essential
      for the copper resistance in P. aeruginosa as well as the activation of ptrA in
      response to the copper signal. Elevated expression of the ptrA during the
      infection of mouse burn wound suggests that P. aeruginosa has evolved tight
      regulatory systems to shut down energy-expensive type III secretion apparatus in
      response to specific environmental signals, such as copper stress.

PMID- 15469506
TI  - Ss-LrpB, a novel Lrp-like regulator of Sulfolobus solfataricus P2, binds
      cooperatively to three conserved targets in its own control region.
AB  - Ss-LrpB, a novel Lrp-like DNA-binding protein from the hyperthermophilic
      crenarchaeon Sulfolobus solfataricus, was shown to bind cooperatively to three
      regularly spaced targets in its own control region, with as consensus the 15 bp
      palindrome 5'-TTGYAW WWWWTRCAA-3'. Binding to the border sites occurred with high
      affinity; the target in the middle proved to be a low affinity site which is
      stably bound only when both flanking sites are occupied. Ss-LrpB contacts two
      major groove segments and the intervening minor groove of each site, all aligned
      on one face of the helix. The operator shows intrinsic bending and is
      increasingly deformed upon binding of Ss-LrpB to one, two and three targets.
      Complex formation relies therefore on DNA conformability, protein-DNA and protein
      protein contacts. Mobility-shift assays and in gel footprinting indicate that Ss
      LrpB and the transcription factors TATA-box binding protein (TBP) and
      transcription factor B (TFB) can bind simultaneously to the control region. Based
      on these findings we present a model for the construction of the higher order
      nucleoprotein complexes and a hypothesis for the autoregulatory process. The
      latter is based on the concentration-dependent formation of distinct complexes
      exhibiting different stoichiometries and conformations, which could positively
      and negatively affect promoter activity.

PMID- 15469507
TI  - Co-ordinate single-cell expression of LEE4- and LEE5-encoded proteins of
      Escherichia coli O157:H7.
AB  - Escherichia coli O157:H7 is a zoonotic pathogen that can express a type III
      secretion system (TTSS) considered important for colonization and persistence in
      ruminants. E. coli O157:H7 strains have been shown to vary markedly in levels of
      protein secreted using the TTSS and this study has confirmed that a high
      secretion phenotype is more prevalent among isolates associated with human
      disease than isolates shed by healthy cattle. The variation in secretion levels
      is a consequence of heterogeneous expression, being dependent on the proportion
      of bacteria in a population that are actively engaged in protein secretion. This
      was demonstrated by indirect immunofluorescence and eGFP fusions that examined
      the expression of locus of enterocyte effacement (LEE)-encoded factors in
      individual bacteria. In liquid media, the expression of EspA, tir::egfp, intimin,
      but not map::egfp were co-ordinated in a subpopulation of bacteria. In contrast
      to E. coli O157:H7, expression of tir::egfp in EPEC E2348/69 was equivalent in
      all bacteria although the same fusion exhibited variable expression when
      transformed into an E. coli O157:H7 background. An E. coli O157:H7 strain deleted
      for the LEE demonstrated weak but variable expression of tir::egfp indicating
      that the elements controlling the heterogeneous expression lie outside the LEE.
      The research also demonstrated the rapid induction of tir::egfp and map::egfp on
      contact with bovine epithelial cells. This control in E. coli O157:H7 may be
      required to limit exposure of key surface antigens, EspA, Tir and intimin during
      colonization of cattle but allow their rapid production on contact with bovine
      gastrointestinal epithelium at the terminal rectum.

PMID- 15469508
TI  - HopPtoN is a Pseudomonas syringae Hrp (type III secretion system) cysteine
      protease effector that suppresses pathogen-induced necrosis associated with both
      compatible and incompatible plant interactions.
AB  - Pseudomonas syringae pv. tomato DC3000 causes bacterial speck disease in tomato,
      and it elicits the hypersensitive response (HR) in non-host plants such as
      Nicotiana tabacum and Nicotiana benthamiana. The compatible and incompatible
      interactions of DC3000 with tomato and Nicotiana spp., respectively, result in
      plant cell death, but the HR cell death occurs more rapidly and is associated
      with effective plant defense. Both interactions require the Hrp (HR and
      pathogenicity) type III secretion system (TTSS), which injects Hop (Hrp outer
      protein) effectors into plant cells. Here, we demonstrate that HopPtoN is
      translocated into tomato cells via the Hrp TTSS. A hopPtoN mutant produced
      eightfold more necrotic 'speck' lesions on tomato leaves than did DC3000, but the
      mutant and the wild-type strain grew to the same level in infected leaves. In non
      host N. tabacum leaves, the hopPtoN mutant produced more cell death, whereas a
      DC3000 strain overexpressing HopPtoN produced less cell death and associated
      electrolyte leakage in comparison with wild-type DC3000. Transient expression of
      HopPtoN via infection with a PVX viral vector enabled tomato and N. benthamiana
      plants to tolerate, with reduced disease lesions, challenge infections with
      DC3000 and P. syringae pv. tabaci 11528, respectively. HopPtoN showed cysteine
      protease activity in vitro, and hopPtoN mutants altered in the predicted cysteine
      protease catalytic triad (C172S, H283A and D299A) lost HR suppression activity.
      These observations reveal that HopPtoN is a TTSS effector that can suppress plant
      cell death events in both compatible and incompatible interactions.

PMID- 15469509
TI  - Multiple variants of the archaeal DNA rudivirus SIRV1 in a single host and a
      novel mechanism of genomic variation.
AB  - The DNA rudivirus SIRV1 of the hyperthermophilic archaeon Sulfolobus shows
      exceptional properties. Viral isolates invariably contain a population of
      variants with different but closely related genomes. Upon propagation in a given
      host strain, one or more genomes dominate in the viral population. However, upon
      passage into a new host strain the viral population undergoes changes and other
      dominant variants are selected. Sequencing and analysis of the variant genomes
      revealed that major differences occur in gene order, gene size and gene content
      at localized genomic sites. A previously unknown mechanism of genomic
      rearrangement involving putative 12 bp archaeal introns appears to facilitate
      alteration of the variant genomes. Inter-genomic recombination between the
      different variants also occurs. The variant genomes exhibit signature
      tetranucleotide sequences near their putative sites for replication initiation.

PMID- 15469510
TI  - Peptide-mediated macrolide resistance reveals possible specific interactions in
      the nascent peptide exit tunnel.
AB  - Expression of specific short peptides can render cells resistant to macrolide
      antibiotics. Peptides conferring resistance to structurally different macrolides
      including oleandomycin, azithromycin, azaerythromycin, josamycin and a ketolide
      cethromycin were selected from a random pentapeptide expression library. Analysis
      of the entire collection of the resistance peptides allowed their classification
      into five distinct groups according to their sequence similarity and the type of
      resistance they confer. A strong correlation was observed between the structures
      of macrolide antibiotics and sequences of the peptides conferring resistance.
      Such a correlation indicates that sequence-specific interactions between the
      nascent peptide and the macrolide antibiotic and/or the ribosome can occur in the
      ribosomal exit tunnel.

PMID- 15469511
TI  - Activation of the RcsC/YojN/RcsB phosphorelay system attenuates Salmonella
      virulence.
AB  - Bacterial pathogens have the ability to sense their presence in host tissues and
      to promote expression of their virulence factors in a time- and location
      dependent manner. However, little is known about those genes whose expression is
      detrimental and thus suppressed during infection. Here we report that
      constitutive activation of the RcsC/YojN/RcsB system resulting from a mutation in
      the rcsC sensor gene dramatically attenuates Salmonella virulence. Mutation of
      the cognate response regulator gene rcsB restored full virulence to the rcsC
      constitutive mutant, indicating that virulence attenuation results from aberrant
      expression of RcsB-regulated genes. The virulence attenuation phenotype was
      partially dependent on the regulatory gene rcsA, which is necessary for
      transcription of certain RcsB-regulated genes, and on the RcsB- and RcsA
      dependent colanic acid capsule synthesis cps operon. The rcsC constitutive mutant
      was phagocytized less efficiently by macrophages and it was defective for
      invasion of non-phagocytic cells and survival within macrophages; but it could
      protect mice upon challenge with wild-type Salmonella. Our results suggest that a
      successful infection demands that pathogens turn off expression of products that
      might interfere with virulence functions.

PMID- 15469512
TI  - The PAK family kinase Cla4 is required for budding and morphogenesis in Ustilago
      maydis.
AB  - The phytopathogenic basidiomycete Ustilago maydis displays a dimorphic switch
      between budding growth of haploid cells and filamentous growth of the dikaryon.
      In a screen for mutants affected in morphogenesis and cytokinesis, we identified
      the serine/threonine protein kinase Cla4, a member of the family of p21-activated
      kinases (PAKs). Cells, in which cla4 has been deleted, are viable but they are
      unable to bud properly. Instead, cla4 mutant cells grow as branched septate
      hyphae and divide by contraction and fission at septal cross walls. Delocalized
      deposition of chitinous cell wall material along the cell surface is observed in
      cla4 mutant cells. Deletion of the Cdc42/Rac1 interaction domain (CRIB) results
      in a constitutive active Cla4 kinase, whose expression is lethal for the cell.
      cla4 mutant cells are unable to induce pathogenic development in plants and to
      display filamentous growth in a mating reaction, although they are still able to
      secrete pheromone and to undergo cell fusion with wild-type cells. We propose
      that Cla4 is involved in the regulation of cell polarity during budding and
      filamentation.

PMID- 15469513
TI  - Cryptococcus neoformans Kin1 protein kinase homologue, identified through a
      Caenorhabditis elegans screen, promotes virulence in mammals.
AB  - Cryptococcal infections are a global cause of significant morbidity and
      mortality. Recent studies support the hypothesis that virulence of Cryptococcus
      neoformans may have evolved via survival selection in environmental hosts, such
      as amoebae and free-living nematodes. We used killing of the nematode
      Caenorhabditis elegans by C. neoformans as an assay to screen a library of random
      C. neoformans insertion mutants. Of 350 mutants tested, seven were identified
      with attenuated virulence that persisted after crossing the mutation back into a
      wild-type strain. Genetic analysis of one strain revealed an insertion in a gene
      homologous to Saccharomyces cerevisiae KIN1, which encodes a serine/threonine
      protein kinase. C. neoformans kin1 mutants exhibited significant defects in
      virulence in murine inhalation and haematogenous infection models and displayed
      increased binding to alveolar and peritoneal macrophages. The kin1 mutant
      phenotypes were complemented by the wild-type KIN1 gene. These findings show that
      the C. neoformans Kin1 kinase homologue is required for full virulence in
      disparate hosts and that C. elegans can be used as a substitute host to identify
      novel factors involved in fungal pathogenesis in mammals.

PMID- 15469514
TI  - Deletion of the genes encoding the MtrA-MtrB two-component system of
      Corynebacterium glutamicum has a strong influence on cell morphology, antibiotics
      susceptibility and expression of genes involved in osmoprotection.
AB  - The MtrAB two-component signal transduction system is highly conserved in
      sequence and genomic organization in Mycobacterium and Corynebacterium species,
      but its function is completely unknown. Here, the role of MtrAB was studied with
      C. glutamicum as model organism. In contrast to M. tuberculosis, it was possible
      to delete the mtrAB genes in C. glutamicum. The mutant cells showed a radically
      different cell morphology and were more sensitive to penicillin, vancomycin and
      lysozyme but more resistant to ethambutol. In order to identify the molecular
      basis for this pleiotropic phenotype, the mRNA profiles of mutant and wild type
      were compared with DNA microarrays. Three genes showed a more than threefold
      increased RNA level in the mutant, i.e. mepA (NCgl2411) encoding a putative
      secreted metalloprotease, ppmA (NCgl2737 ) encoding a putative membrane-bound
      protease modulator, and lpqB encoding a putative lipoprotein of unknown function.
      Expression of plasmid-encoded mepA in Escherichia coli led to elongated cells
      that were hypersensitive to an osmotic downshift, supporting the idea that
      peptidoglycan is the target of MepA. The mRNA level of two genes was more than
      fivefold decreased in the mutant, i.e. betP and proP which encode transporters
      for the uptake of betaine and proline respectively. The microarray results were
      confirmed by primer extension and RNA dot blot experiments. In the latter, the
      transcript level of genes involved in osmoprotection was tested before and after
      an osmotic upshift. The mRNA level of betP, proP and lcoP was strongly reduced or
      undetectable in the mutant, whereas that of mscL (mechanosensitive channel) was
      increased. The changes in cell morphology, antibiotics susceptibility and the
      mRNA levels of betP, proP, lcoP, mscL and mepA could be reversed by expression of
      plasmid-encoded copies of mtrAB in the DeltamtrAB mutant, confirming that these
      changes occurred as a consequence of the mtrAB deletion.

PMID- 15469515
TI  - Distinctive genetic features exhibited by the Y-family DNA polymerases in
      Bacillus subtilis.
AB  - Translesional DNA polymerases form a large family of structurally related
      proteins, known as the Y-polymerases. Bacillus subtilis encodes two Y
      polymerases, referred herewith as Pol Y1 and Pol Y2. Pol Y1 was expressed
      constitutively and did not mediate UV mutagenesis. Pol Y1 overexpression
      increased spontaneous mutagenesis. This effect depended on Pol Y1 polymerase
      activity, Pol Y1 interaction with the beta-clamp, and did not require the
      presence of the RecA protein. In addition, Pol Y1 overexpression delayed cell
      growth at low temperature. The growth delay was mediated by Pol Y1 interaction
      with the beta-clamp but not by its polymerase activity, suggesting that an excess
      of Pol Y1 in the cell could sequester the beta-clamp. In contrast, Pol Y2 was
      expressed during the SOS response, and, in its absence, UV-induced mutagenesis
      was abolished. Upon Pol Y2 overproduction, both UV-induced and spontaneous
      mutagenesis were stimulated, and both depended on the Pol Y2 polymerase activity.
      However, UV mutagenesis did not appear to require the interaction of Pol Y2 with
      the beta-clamp whereas spontaneous mutagenesis did. In addition, Pol Y2-mediated
      spontaneous mutagenesis required the presence of RecA. Together, these results
      show that the regulation and the genetic requirements of the two B. subtilis Y
      polymerases are different, indicating that they fulfil distinct biological roles.
      Remarkably, Pol Y1 appears to exhibit a mutator activity similar to that of
      Escherichia coli Pol IV, as well as an E. coli UmuD-related function in growth
      delay. Pol Y2 exhibits an E. coli Pol V-like mutator activity, but probably acts
      as a single polypeptide to bypass UV lesions. Thus, B. subtilis Pol Y1 and Pol Y2
      exhibit distinctive features from the E. coli Y-polymerases, indicating that
      different bacteria have adapted different solutions to deal with the lesions in
      their genetic material.

PMID- 15469516
TI  - The midcell replication factory in Bacillus subtilis is highly mobile:
      implications for coordinating chromosome replication with other cell cycle
      events.
AB  - During vegetative growth, rod-shaped bacterial cells such as Escherichia coli and
      Bacillus subtilis divide precisely at midcell. It is the Z ring that defines the
      position of the division site. We previously demonstrated that the early stages
      of chromosome replication are linked to midcell Z ring assembly in B. subtilis
      and proposed a direct role for the centrally located replication factory in
      masking and subsequently unmasking the midcell site for Z ring assembly. We now
      show that the replication factory is significantly more scattered about the cell
      centre than the Z ring in both vegetative cells and outgrown spores of B.
      subtilis. This finding is inconsistent with the midcell replication factory
      acting as a direct physical block to Z ring assembly. Time-lapse experiments
      demonstrated that the lower precision of replication factory positioning results
      from its high mobility around the cell centre. Various aspects of this mobility
      are presented and the results are discussed in the light of current views on the
      determinants of positional information required for accurate chromosome
      segregation and cell division.

PMID- 15469517
TI  - Characterization of a lipoprotein, NilC, required by Xenorhabdus nematophila for
      mutualism with its nematode host.
AB  - Xenorhabdus nematophila is a gamma-proteobacterial mutualist of an insect
      pathogenic nematode, Steinernema carpocapsae. X. nematophila requires nilC, a
      gene predicted to encode an outer membrane lipoprotein of unknown function, for
      colonization of its nematode host. Characterization of NilC, described here,
      demonstrated it is a 28 kDa lipoprotein directed to the periplasm by an N
      terminal signal sequence. Lipidation and processing of NilC occurs by a mechanism
      that is conserved in proteobacteria. This work also showed NilC is membrane
      associated and oriented towards the periplasm of X. nematophila and is produced
      as an outer membrane-associated protein when expressed in Escherichia coli.
      Expression analyses revealed that nilC transcription is directly or indirectly
      repressed by Lrp, and this regulatory link may explain the nematode mutualism
      defect of a previously identified lrp::Tn5 mutant. An lrp::Tn5 mutant produces an
      additional nilC transcript, not observed in wild-type cells growing in vitro, and
      produces approximately 75-fold more nilC than wild-type cells in late stationary
      phase. These fundamental characterizations of nilC expression and nilC
      localization and processing events have provided firm bases for understanding the
      role of this colonization factor in the X. nematophila/S. carpocapsae microbe
      host interaction.

PMID- 15469518
TI  - Analysis of the N-terminal DNA binding domain of the IS30 transposase.
AB  - IS30 is the founding member of a large family of widely spread bacterial
      insertion sequences with closely related transposases. The N-terminal end of the
      IS30 transposase had been shown to retain sequence-specific DNA binding activity
      and to protect the IS30 terminal inverted repeats. Structural predictions
      revealed the presence of a helix-helix-turn-helix motif (H-HTH2) which, in the
      case of IS30, is preceded by an additional helix-turn-helix motif (HTH1).
      Analysis of deletion and point mutants in this region revealed that both motifs
      are important for IS30 transposition. IS30 exhibits two types of insertion
      specificity preferring either a 24 bp palindromic hot-spot (GOHS) or sequences
      resembling its ends [left and right terminal inverted repeat (IRL and IRR)].
      Results are presented suggesting that the HTH1 region is required for GOHS
      targeting and interferes with the inverted repeat (IR) targeting. On the other
      hand, H-HTH2 appears to be required for both. The binding activities of the
      mutant proteins to the terminal IS30 IRs as measured by gel retardation
      correlated well with these results. Furthermore, close inspection of the H-HTH2
      region revealed significant amino acid identity with a similar predicted
      secondary structure carried by the transcriptional regulator FixJ of
      Sinorhizobium meliloti and involved in FixJ binding to its target sequence. This
      suggests that FixJ and IS30 transposase share similar sequence-specific DNA
      binding mechanisms.

PMID- 15469519
TI  - Communication between Esigma(54) , promoter DNA and the conserved threonine
      residue in the GAFTGA motif of the PspF sigma-dependent activator during
      transcription activation.
AB  - Conversion of Esigma(54) closed promoter complexes to open promoter complexes
      requires specialized activators which are members of the AAA (ATPases Associated
      with various cellular Activities) protein family. The ATP binding and hydrolysis
      activity of Esigma(54) activators is used in an energy coupling reaction to
      remodel the Esigma(54) closed promoter complex and to overcome the sigma(54)
      imposed block on open complex formation. The remodelling target for the AAA
      activator within the Esigma(54) closed complex includes a complex interface
      contributed to by Region I of sigma(54), core RNA polymerase and a promoter DNA
      fork junction structure, comprising the Esigma(54) regulatory centre. One
      sigma(54) binding surface on Esigma(54) activators is a conserved sequence known
      as the GAFTGA motif. Here, we present a detailed characterization of the
      interaction between Region I of sigma(54) and the Escherichia coli AAA sigma(54)
      activator Phage shock protein F. Using Esigma(54) promoter complexes that mimic
      different conformations adopted by the DNA during open complex formation, we
      investigated the contribution of the conserved threonine residue in the GAFTGA
      motif to transcription activation. Our results suggest that the organization of
      the Esigma(54) regulatory centre, and in particular the conformation adopted by
      the sigma(54) Region I and the DNA fork junction structure during open complex
      formation, is communicated to the AAA activator via the conserved T residue of
      the GAFTGA motif.

PMID- 15469520
TI  - Candida albicans lacking the frataxin homologue: a relevant yeast model for
      studying the role of frataxin.
AB  - We cloned the CaYFH1 gene that encodes the yeast frataxin homologue in Candida
      albicans. CaYFH1 was expressed in Deltayfh1 Saccharomyces cerevisiae cells, where
      it compensated for all the phenotypes tested except for the lack of cytochromes.
      Double DeltaCayfh1/DeltaCayfh1 mutant had severe defective growth, accumulated
      iron in their mitochondria, lacked aconitase and succinate dehydrogenase activity
      and had defective respiration. The reductive, siderophore and haem uptake systems
      were constitutively induced and the cells excreted flavins, thus behaving like
      iron-deprived wild-type cells. Mutant cells accumulated reactive oxygen species
      and were hypersensitive to oxidative stress, but not to iron. Cytochromes were
      less abundant in mutants than in wild-type cells, but this did not result from
      defective haem synthesis. The low cytochrome concentration in mutant cells was
      comparable to that of iron-deprived wild-type cells. Mitochondrial iron was still
      available for haem synthesis in DeltaCayfh1/DeltaCayfh1 cells, in contrast to S.
      cerevisaeDeltayfh1 cells. CaYFH1 transcription was strongly induced by iron,
      which is consistent with a role of CaYfh1 in iron storage. Iron also regulated
      transcription of CaHEM14 (encoding protoporphyrinogen oxidase) but not that of
      CaHEM15 (encoding ferrochelatase). There are thus profound differences between S.
      cerevisiae and C. albicans in terms of haem synthesis, cytochrome turnover and
      the role of frataxin in these processes.

PMID- 15469521
TI  - Enterococcus faecalis pheromone-responsive protein PrgX: genetic separation of
      positive autoregulatory functions from those involved in negative regulation of
      conjugative plasmid transfer.
AB  - The pCF10 plasmid in Enterococcus faecalis transfers from donor cells to
      recipients upon induction via peptide pheromone. Two plasmid-encoded negative
      regulators produced from the same transcript, PrgX protein and Qa RNA, repress
      conjugation genes in uninduced donor cells. PrgX positively autoregulates
      production of both itself and mature Qa RNA, and is believed to repress the prgQ
      promoter in a pheromone-sensitive fashion. Previous analysis of PrgX was
      complicated because mutations in prgX affecting regulation of conjugation also
      disrupted PrgX autoregulation, suggesting the two functions might be inseparable.
      In this study, we isolated 14 single amino acid substitutions in PrgX that
      reduced or eliminated repression of prgQ, without affecting autoregulation or DNA
      binding. PrgX was shown to bind to its cognate pheromone, cCF10, and most of the
      mutations lowered the affinity of PrgX for cCF10. Dimerization was affected by
      five of the mutations and the data indicate that it is required, but insufficient
      for pheromone induction. We propose a new model for the mechanism used by PrgX
      for regulation of the prgQ promoter, PrgX autoregulation, and Qa RNA processing.

PMID- 15469522
TI  - Cladosporium fulvum circumvents the second functional resistance gene homologue
      at the Cf-4 locus (Hcr9-4E ) by secretion of a stable avr4E isoform.
AB  - Introgression of resistance trait Cf-4 from wild tomato species into tomato
      cultivar MoneyMaker (MM-Cf0) has resulted in the near-isogenic line MM-Cf4 that
      confers resistance to the fungal tomato pathogen Cladosporium fulvum. At the Cf-4
      locus, five homologues of Cladosporium resistance gene Cf-9 (Hcr9s) are present.
      While Hcr9-4D represents the functional Cf-4 resistance gene matching Avr4, Hcr9
      4E confers resistance towards C. fulvum by mediating recognition of the novel
      avirulence determinant Avr4E. Here, we report the isolation of the Avr4E gene,
      which encodes a cysteine-rich protein of 101 amino acids that is secreted by C.
      fulvum during colonization of the apoplastic space of tomato leaves. By
      complementation we show that Avr4E confers avirulence to strains of C. fulvum
      that are normally virulent on Hcr9-4E-transgenic plants, indicating that Avr4E is
      a genuine, race-specific avirulence determinant. Strains of C. fulvum evade Hcr9
      4E-mediated resistance either by a deletion of the Avr4E gene or by production of
      a stable Avr4E mutant protein that carries two amino acid substitutions,
      Phe(82)Leu and Met(93)Thr. Moreover, we demonstrate by site-directed mutagenesis
      that the single amino acid substitution Phe(82)Leu in Avr4E is sufficient to
      evade Hcr9-4E-mediated resistance.

PMID- 15469523
TI  - A regulation cascade controls expression of Porphyromonas gingivalis fimbriae via
      the FimR response regulator.
AB  - Little is known about how Porphyromonas gingivalis, a Gram-negative oral
      anaerobe, senses environmental changes, and how such information is transmitted
      to the cell. The production of P. gingivalis surface fimbriae is regulated by
      FimS-FimR, a two component signal transduction system. Expression of fimA,
      encoding the fimbrilin protein subunit of fimbriae, is positively regulated by
      the FimR response regulator. In this study we investigated the molecular
      mechanisms of FimR regulation of fimA expression. Comparative transcription
      profiling of fimR wild-type and mutant strains shows that FimR controls the
      expression of several genes including five clustered around the fimA locus.
      Chromatin immunoprecipitation assays and electrophoretic mobility shift assays
      identify and confirm that FimR binds to the promoter region of the first gene in
      the fimA cluster. Gene expression analyses of mutant strains reveal a
      transcriptional cascade involving multiple steps, with FimR activating expression
      of the first gene of the cluster that encodes a key regulatory protein.

PMID- 15469524
TI  - Symbiotic phenotypes and translocated effector proteins of the Mesorhizobium loti
      strain R7A VirB/D4 type IV secretion system.
AB  - The symbiosis island of Mesorhizobium loti strain R7A contains genes with strong
      similarity to the structural vir genes (virB1-11; virD4) of Agrobacterium
      tumefaciens that encode the type IV secretion system (T4SS) required for T-DNA
      transfer to plants. In contrast, M. loti strain MAFF303099 lacks these genes but
      contains genes not present in strain R7A that encode a type III secretion system
      (T3SS). Here we show by hybridization analysis that most M. loti strains contain
      the VirB/D4 T4SS and not the T3SS. Strikingly, strain R7A vir gene mutants formed
      large nodules containing bacteroids on Leucaena leucocephala in contrast to the
      wild-type strain that formed only uninfected tumour-like structures. A rhcJ T3SS
      mutant of strain MAFF303099 also nodulated L. leucocephala, unlike the wild type.
      On Lotus corniculatus, the vir mutants were delayed in nodulation and were less
      competitive compared with the wild type. Two strain R7A genes, msi059 and msi061,
      were identified through their mutant phenotypes as possibly encoding translocated
      effector proteins. Both Msi059 and Msi061 were translocated through the A.
      tumefaciens VirB/D4 system into Saccharomyces cerevisiae and Arabidopsis
      thaliana, as shown using the Cre recombinase Reporter Assay for Translocation
      (CRAfT). Taken together, these results suggest that the VirB/D4 T4SS of M. loti
      R7A plays an analogous symbiotic role to that of T3SS found in other rhizobia.
      The heterologous translocation of rhizobial proteins by the Agrobacterium VirB/D4
      T4SS is the first demonstration that rhizobial effector proteins are translocated
      into plant cells and confirms functional conservation between the M. loti and A.
      tumefaciens T4SS.

PMID- 15469525
TI  - Predictive genetic testing in young people: when is it appropriate?
AB  - Predictive genetic testing is currently offered to adults for a range of
      conditions, even when there is no possibility of prophylaxis or treatment.
      However, similar testing in children and adolescents is advised against in
      international guidelines. Despite this, several authors have argued against the
      existing guidelines. Given the lack of empirical evidence, it is important that
      clinicians are aware not only of the guidelines, but also of the arguments in
      favour of such testing.

PMID- 15469526
TI  - Primary adrenal insufficiency in childhood and adolescence: advances in diagnosis
      and management.
AB  - OBJECTIVES: Primary adrenal insufficiency occurring in childhood and adolescence
      is due to abnormalities of gland development, gland responsiveness, and steroid
      biosynthesis or target organ response. Causes include autoimmune Addison's
      disease, tuberculosis, HIV, adrenoleukodystrophy, adrenal hypoplasia congenita
      and syndromes including triple A and IMAGe. We aimed to define the causes of
      adrenal insufficiency for a cohort of children in Melbourne. METHODS: We reviewed
      the frequency and variety of presentation of primary adrenal insufficiency to the
      Royal Children's Hospital over the past 10 years through an audit of patient
      records, collating demographic information, presentation and investigations.
      RESULTS: Sixteen cases (13 male, 3 female) of primary adrenal insufficiency were
      diagnosed at this hospital between January 1993 and July 2003. Median age at
      presentation was 7.7 years (range: birth to 14.8 years). Symptoms at presentation
      included weakness, increased pigmentation, abdominal pain, nausea, developmental
      delay or a reduction in school performance. Four patients presented with adrenal
      crisis. Median adrenocorticotrophic hormone (ACTH) at diagnosis was 246 pmol/L
      (range 30-969 pmol/L). Autoantibodies were positive in five patients. Five
      patients had elevation of very long chain fatty acids. Five patients were
      diagnosed with autoimmune adrenal insufficiency, five with adrenal hypoplasia
      congenita, five with adrenoleukodystrophy and one with IMAGe syndrome.
      CONCLUSIONS: A high index of suspicion results in earlier detection and possible
      prevention of adrenal crisis with a reduction in associated morbidities.
      Definitive diagnosis is now possible for almost all cases of primary adrenal
      insufficiency using technologies for screening autoimmunity, adrenoleukodystrophy
      (ALD) and genetic screening.

PMID- 15469527
TI  - Management of tongue-tie in children: a survey of paediatric surgeons in
      Australia.
AB  - OBJECTIVES: To explore the beliefs and practices of Australian surgeons regarding
      surgical intervention to release tongue-tie and to determine the main referral
      sources. In addition, we aimed to ascertain if there were differences in beliefs
      and practices according to surgical specialty. METHODS: Four hundred surgeons in
      three different surgical specialties were surveyed via questionnaire. Multiple
      choice response questions and open ended questions were used to explore beliefs
      and practices surrounding tongue-tie assessment, management and follow up. The
      questionnaires were distributed by email (where available), followed by fax and
      mail. RESULTS: A response rate of 80.8% (n = 323) was obtained. Of these, 236
      (73%) reported they practised surgery to release tongue-tie; 46% were oral and
      maxillofacial surgeons, 37% were plastic surgeons and 17% were paediatric general
      surgeons. Indications for surgical management and follow up varied according to
      surgical specialty. There was no clear consensus regarding clinical indicators
      for surgery or functional outcomes following surgery. CONCLUSIONS: It appears
      that until a prospective study designed to address some of the controversial
      issues outlined is undertaken, we will remain ignorant about the need for surgery
      to release tongue-tie in children.

PMID- 15469528
TI  - Pneumococcal meningitis: clinical course and resource use in Western Australian
      children.
AB  - OBJECTIVES: Paediatric pneumococcal meningitis causes high rates of neurological
      sequelae and is presenting challenges due to the emergence of antibiotic
      resistance. Diagnosis can be difficult and management is frequently complicated
      and resource intensive. This population-based study outlines the diagnosis,
      clinical course and initial resource use of Western Australian (WA) children
      diagnosed between 1990 and 2000. METHODS: The charts of all rural and
      metropolitan children discharged from all WA hospitals with International
      Classification of Disease 9 and 10 codes of pneumococcal or streptococcal
      meningitis from the Health Department's Hospital Morbidity Data System were
      reviewed retrospectively. RESULTS: Ninety-four episodes of pneumococcal
      meningitis were confirmed (median age 12.4 months). Initial diagnosis was often
      difficult with a suggestive prodrome in less than one quarter of cases and a
      median of two reviews until diagnosis (range 1-7). The median duration of
      hospitalization was 11.6 days, 41.5% were admitted to the Intensive Care Unit
      (ICU), and 47.9% had seizures. There were eight related deaths and neurological
      sequelae occurred in 24. Initial hospitalization cost on average $A 19,900.
      Penicillin resistance was first noted in 1993 and occurred in 4.6% of isolates.
      Most cases (84.5%) were caused by serotypes contained in the currently available
      seven-valent conjugate vaccine. CONCLUSIONS: Pneumococcal meningitis is often
      difficult to diagnose, necessitates long and frequently complicated in-patient
      stays and has high rates of neurological sequelae. It is possible to prevent most
      cases with new conjugate vaccines.

PMID- 15469529
TI  - Pneumococcal meningitis in Western Australian children: epidemiology,
      microbiology and outcome.
AB  - OBJECTIVES: Pneumococcal meningitis is now vaccine-preventable but continues to
      cause high rates of neurological sequelae internationally. Population-based
      epidemiology, outcome and microbiology data are necessary to target vaccination
      strategies. This study outlines these key areas for Western Australian children
      diagnosed 1990-2000. METHODS: The charts of all rural and metropolitan children
      with International Classification of Disease 9 and 10 discharge codes of
      pneumococcal or streptococcal meningitis from the Health Department's Hospital
      Morbidity Data System were reviewed. RESULTS: Over 10.5 years, 94 episodes were
      confirmed. The average annual incidence for children under 2 years was 13.45 per
      100 000 and 0.66 per 100 000 for children 2 years or older. Indigenous children
      had an almost seven-fold increased risk compared to non-Indigenous (with 78.55
      per 100 000 in the under two-year Indigenous group). Eight children died and 24
      of the survivors had neurological sequelae. Penicillin resistance occurred in
      four of 87 isolates. One quarter of the cohort qualify under the current
      Australian policy of vaccination of high-risk children with seven-valent
      conjugate (7vPCV) vaccine. Most isolates (49/58) were 7vPCV serotypes, however,
      Indigenous populations were less well-covered (58.3% covered vs 91.3% of isolates
      from non-Indigenous children). Indigenous coverage would be improved to 75% with
      11-valent conjugate vaccine. CONCLUSIONS: Indigenous children and those under 2
      years are most affected by pneumococcal meningitis and remain primary vaccination
      targets. Three quarters of these children would not be protected by a policy of
      vaccination of only high-risk children with 7vPCV--improved protection requires
      higher valencies for Indigenous populations and universal infant vaccination.

PMID- 15469530
TI  - Head lice prevalence in primary schools in Victoria, Australia.
AB  - OBJECTIVES: To determine the prevalence of and assess risk factors associated
      with head lice infections (pediculosis) in children from government primary
      schools in Victoria, Australia. METHODS: Between May and October 2001, children
      were selected by clustered random sampling of schools and classes, then examined
      for head lice using hair conditioner and a fine-toothed head lice comb. There
      were 1838 children screened from 16 primary schools. Risk factors evaluated
      included metropolitan or rural residence, school class, gender and hair length.
      RESULTS: Thirteen percent of children (239/1838) had an active infection (95% CI,
      10.9-15.1) and 3.3% (61/1838) had an inactive infection (95% CI, 2.0-4.6).
      Prevalence of active pediculosis varied between schools from 0 to 28%. Our
      screening identified no more than one case per class in the majority of classes
      screened (58.5%). Females were 2.2 times more likely to have active infection
      than males (95% CI [1.7,2.9]) and there was no significant difference for the
      other risk factors investigated. CONCLUSIONS: Our study demonstrated the
      prevalence of head lice varied across Victoria and showed that risk factors
      commonly attributed to head lice infections did not hold true. Our findings
      support the premise that traditional ad hoc mass school-based screening may not
      be the best use of resources when controlling head lice. We suggest a more
      pragmatic community-based approach.

PMID- 15469531
TI  - Oral glucose tolerance test in children and adolescents: positives and pitfalls.
AB  - OBJECTIVES: To describe the glycaemic status (assessed by an oral glucose
      tolerance test (OGTT)) and associated comorbidities in a cohort of Australian
      children and adolescents at risk of insulin resistance and impaired glucose
      homeostasis (IGH). METHODS: Twenty-one children and adolescents (three male, 18
      female) (18 Caucasian, one Indigenous, two Asian) (20 obese, one lipodystrophy)
      referred to the Paediatric Endocrinology and Diabetes Clinic underwent a 2-h OGTT
      with plasma glucose and insulin measured at baseline, + 60 and + 120 min. If
      abnormal, the OGTT was repeated. RESULTS: The mean (SD) age was 14.2 (1.6) years,
      BMI 38.8 (7.0) kg/m2 and BMI-SDS 3.6 (0.6). Fourteen patients had fasting insulin
      levels >21 mU/L. Type 2 diabetes mellitus was diagnosed in one patient, impaired
      glucose tolerance (IGT) in four patients and impaired fasting glycaemia (IFG) in
      one patient. Despite no weight loss, only one patient had a persistently abnormal
      OGTT on repeat testing. Three patients with IGH were medicated with risperidone
      at the time of the initial OGTT. One patient who had persistent IGT had continued
      risperidone. The other two patients had initial OGTT results of IGT and diabetes
      mellitus type 2. They both ceased risperidone between tests and repeat OGTT
      showed normal glycaemic status. CONCLUSIONS: Use of fasting glucose alone may
      miss cases of IGH. Diagnosis of IGT should not be made on one test alone.
      Interpretation of glucose and insulin responses in young people is limited by
      lack of normative data. Larger studies are needed to generate Australian
      screening recommendations. Further assessment of the potential adverse effects of
      atypical antipsychotic medication on glucose homeostasis in this at-risk group is
      important.

PMID- 15469532
TI  - Increased rates of ENT surgery among young children: have clinical guidelines
      made a difference?
AB  - OBJECTIVES: To examine the association between introduction of paediatric ear,
      nose and throat (ENT) surgery guidelines and population procedure rates. To
      determine changes in children's risk of undergoing ENT surgery. METHODS: Trend
      analysis of incidence of myringotomy, tonsillectomy and adenoidectomy among New
      South Wales (NSW) children aged 0-14 between 1981 and mid 1999. Poisson
      regression models were used to estimate annual rates of change pre and
      postguidelines introduction and age/gender specific rates, and lifetable methods
      to determine risk of undergoing an ENT procedure by age 15. RESULTS: ENT surgery
      rates increased by 21% over the study period. Children's risk of surgery
      increased from 17.9% in 1981 to 20.2% in 1998/99. Guideline introduction was
      associated with moderate short-term decreases in rates. For tonsillectomy, rates
      decreased between 1981 and 1983, but then rose continually until the introduction
      of myringotomy guidelines in 1993, when they fell, only to recommence rising
      until the end of the study period. For myringotomy, rates rose annually from 1981
      to 1992/93 and fell in the 3 years following guideline introduction, after which
      they rose again. Increases were almost exclusively restricted to children aged 0
      4 and correspond with increased use of formal childcare. The prevalence of
      myringotomy by the age of 5 years rose from 5.6% of children born in 1988/89 to
      6.4% of those born in 1994/95, and the prevalence of tonsillectomy from 2.4% to
      2.7%. CONCLUSIONS: The risk of young Australian children undergoing ENT surgery
      increased significantly over the last two decades despite the introduction of
      guidelines and no evidence of an increase in otitis media, one condition
      prompting surgery. Surgery increased most among the very young. We hypothesize
      this is related to increasing use of childcare.

PMID- 15469533
TI  - Oxidant and antioxidant levels in preterm newborns with idiopathic
      hyperbilirubinaemia.
AB  - OBJECTIVES: Newborns, particularly preterm infants, have limited antioxidant
      protective capacity. The organism's defence system against reactive oxygen
      species including vitamins A, E and C, trace element selenium (Se) and enzymes,
      such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase
      (GSH-Px) are essential components of the antioxidant system against the oxidative
      injury to the cellular membranes of erythrocytes. In this study, our aim was to
      compare the oxidant nitric oxide (total plasma nitrite level as an indicator of
      nitric oxide (NO)), antioxidant vitamins and selenium and erythrocyte antioxidant
      enzymes in premature babies with hyperbilirubinaemia with healthy preterms.
      METHODS: Twenty preterm infants with newborn jaundice were included in the study
      group, while 15 preterm infants without jaundice were enrolled in the control
      group. We evaluated the mean plasma levels of, respectively, the total nitrite as
      an indicator of NO, bilirubin, vitamins A, E, C and selenium, and the activity of
      erythrocyte antioxidant enzymes such as CAT, SOD and GSH-Px of preterm infants
      with idiopathic hyperbilirubinaemia and compared to those of the control group.
      RESULTS: The mean plasma total nitrite and total serum bilirubin levels and blood
      reticulocyte counts of the study group were found to be significantly higher than
      those of the control group (P < 0.001, P < 0.001 and P < 0.05, respectively).
      Furthermore, the activity of erythrocyte antioxidant enzymes (all P < 0.001) and
      the mean plasma levels of the antioxidant vitamins A, E, and C (P < 0.05, P <
      0.05 and P < 0.001, respectively) and selenium (P < 0.001) of the study group
      were all found to be significantly lower than those of the control group.
      CONCLUSION: We hypothesize that low antioxidants in pretem babies may predispose
      them to increased oxidative stress, and cause hyperbilirubinaemia.

PMID- 15469536
TI  - Macro-AST: a benign cause of persistently elevated aspartate aminotransferase.

PMID- 15469535
TI  - Child booster seats and lethal seat belt injury.
AB  - A 7-year-old boy travelling in the rear seat of a sedan car was wearing a lap
      shoulder seat belt and sitting on a booster seat. Following a collision the boy
      'submarined' under the seat belt sustaining trauma to the anterior aspect of his
      neck, cardiac arrest and subsequent death from hypoxic-ischaemic encephalopathy.
      This case demonstrates a potential problem with unsecured older-style booster
      seats. Movement of a seat in a collision may cause a child to slip under a seat
      belt and sustain significant neck injuries. Seatbelts for children must be
      correctly fitted, booster seats or capsules must be securely fastened and
      manufacturer's recommendations for size and weight limits should be followed.
      Unfortunately older booster seats may not have attached instructions for
      installation and use, may not fit later model vehicles, may not conform to
      current safety recommendations and may have worn webbing. For these reasons their
      use should be discouraged.

PMID- 15469537
TI  - Addison's disease presenting with an acute abdomen and complicated by
      cardiomyopathy.
AB  - Adrenal insufficiency typically presents with non-specific symptoms, followed by
      shock secondary to a salt-wasting crisis and/or the vascular effects of
      glucocorticoid deficiency if it progresses to acute adrenal insufficiency.
      Rhabdomyolysis and cardiac dysfunction are rarely reported, particularly in
      children. We report a child with adrenal insufficiency, presenting with acute
      abdominal signs, probably secondary to rhabdomyolysis, and complicated by
      reversible cardiomyopathy. Acute adrenal insufficiency should be considered with
      this presentation. The possibility of impaired cardiac function during its
      treatment should also be considered.

PMID- 15469538
TI  - Hypercalcaemia and hypertransaminasaemia in a child with hyperthyroidism.
AB  - Hypercalcaemia and hypertransaminasaemia are well recognized and not infrequent
      findings in hyperthyroidism in adults. Both conditions are seldom reported in
      children. Here we report the case of a 4-year-old girl with hyperthyroidism
      associated with hypercalcaemia and hypertransaminasaemia which were reversed
      after euthyroid state was achieved. We recommend that serum calcium and liver
      function should always be monitored in children with hyperthyroidism.

PMID- 15469539
TI  - Perforation of jejunal duplication lined with ectopic gastric mucosa.
AB  - Alimentary tract duplications are rare congenital anomalies that occasionally
      contain ectopic gastric mucosa that secretes acid peptic juice and can cause
      pain, ulceration, bleeding and rarely perforation. We report a case of a 2-year
      old girl who developed perforation of a jejunal duplication lined with ectopic
      gastric mucosa who was managed surgically.

PMID- 15469540
TI  - Use of the newborn screening card to define cause of death in a 12-year-old
      diagnosed with epilepsy.
AB  - Post-mortem investigation of sudden death in young people frequently reveals no
      overt cause for the death. Full investigation is hampered if tissue or blood is
      not retained for DNA analysis. We report a post mortem molecular diagnosis of
      long QT syndrome in a 12-year-old boy diagnosed with epilepsy who died suddenly
      playing sport. The DNA was extracted from an archived blood spot on his newborn
      screening ('Guthrie') card, which had been taken from him at 6 days of age. A
      missense mutation was detected in exon 5 of the KCNQ1 gene; R243C (835C > T),
      associated with long QT type 1. The same mutation was found in the mother (who
      now takes effective preventative therapy), but not in the sib who has now been
      reassured that she is not at risk of sudden death.

PMID- 15469541
TI  - Congenital cystic adenomatoid malformation: importance of postnatal chest
      computed tomography scans.

PMID- 15469542
TI  - Severe labial fusion as a temporary contraindication to voiding cystourethrogram.

PMID- 15469548
TI  - The CARI guidelines. Urine protein as diagnostic test: evaluation of proteinuria
      in children.

PMID- 15469549
TI  - The CARI guidelines. Urine protein as diagnostic test: monitoring proteinuria in
      patients with suspected or known renal disease.

PMID- 15469550
TI  - The CARI guidelines. CMV disease and kidney transplant: diagnostic tests for
      cytomegalovirus in renal transplantation.

PMID- 15469551
TI  - The CARI guidelines. CMV disease and kidney transplant: prophylaxis for
      cytomegalovirus infection in patients following renal transplantation.

PMID- 15469552
TI  - The CARI guidelines. Urine protein as diagnostic test: testing for proteinuria.

PMID- 15469553
TI  - The CARI guidelines. CMV disease and kidney transplant: pre-emptive treatment of
      cytomegalovirus.

PMID- 15469554
TI  - The CARI guidelines. CMV disease and kidney transplant: treatment of
      cytomegalovirus disease in renal transplant recipients.

PMID- 15469555
TI  - The CARI guidelines. Evidence for peritonitis treatment and prophylaxis: the
      influence of peritoneal dialysis systems and solutions on the incidence of
      peritonitis and catheter-related infections.

PMID- 15469556
TI  - The CARI guidelines. Evidence for peritonitis treatment and prophylaxis:
      peritoneal dialysis-associated peritonitis in children.

PMID- 15469557
TI  - The CARI guidelines. Evidence for peritonitis treatment and prophylaxis:
      indications for recommencement of peritoneal dialysis after treatment for
      peritonitis.

PMID- 15469558
TI  - The CARI guidelines. Evidence for peritonitis treatment and prophylaxis:
      indications for the removal of peritoneal dialysis catheters.

PMID- 15469559
TI  - The CARI guidelines. Evidence for peritonitis treatment and prophylaxis:
      indications for the use of urokinase in peritoneal dialysis-associated
      peritonitis.

PMID- 15469560
TI  - The CARI guidelines. Evidence for peritonitis treatment and prophylaxis: type of
      peritoneal dialysis catheter.

PMID- 15469561
TI  - The CARI guidelines. Evidence for peritonitis treatment and prophylaxis:
      technique of insertion of peritoneal dialysis catheter.

PMID- 15469562
TI  - The CARI guidelines. Evidence for peritonitis treatment and prophylaxis:
      prophylactic antibiotics for insertion of peritoneal dialysis catheter.

PMID- 15469563
TI  - The CARI guidelines. Evidence for peritonitis treatment and prophylaxis: timing
      of commencement of dialysis after peritoneal dialysis catheter insertion.

PMID- 15469564
TI  - The CARI guidelines. Evidence for peritonitis treatment and prophylaxis:
      treatment of peritoneal dialysis-associated fungal peritonitis.

PMID- 15469565
TI  - The CARI guidelines. Urine protein as diagnostic test: performance
      characteristics of tests used in the initial evaluation of patients at risk of
      renal disease.

PMID- 15469566
TI  - The CARI guidelines. Evidence for peritonitis treatment and prophylaxis:
      peritoneal dialysis catheter-related infection: exit site and tunnel.

PMID- 15469567
TI  - The CARI guidelines. Evidence for peritonitis treatment and prophylaxis:
      prophylaxis for exit site/tunnel infections using mupirocin.

PMID- 15469568
TI  - The CARI guidelines. Evidence for peritonitis treatment and prophylaxis:
      treatment of peritoneal dialysis-associated peritonitis in adults.

PMID- 15469569
TI  - In vitro and in vivo evaluation of a new active heat moisture exchanger.
AB  - INTRODUCTION: In order to improve the efficiency of heat moisture exchangers
      (HMEs), new hybrid humidifiers (active HMEs) that add water and heat to HMEs have
      been developed. In this study we evaluated the efficiency, both in vitro and in
      vivo, of a new active HME (the Performer; StarMed, Mirandola, Italy) as compared
      with that of existing HMEs (Hygroster and Hygrobac; Mallinckrodt, Mirandola,
      Italy). METHODS: We tested the efficiency by measuring the temperature and
      absolute humidity (AH) in vitro using a test lung ventilated at three levels of
      minute ventilation (5, 10 and 15 l/min) and at two tidal volumes (0.5 and 1 l),
      and in vivo in 42 patients with acute lung injury (arterial oxygen
      tension/fractional inspired oxygen ratio 283 +/- 72 mmHg). We also evaluated the
      efficiency in vivo after 12 hours. RESULTS: In vitro, passive Performer and
      Hygrobac had higher airway temperature and AH (29.2 +/- 0.7 degrees C and 29.2 +/
      0.5 degrees C, [P < 0.05]; AH: 28.9 +/- 1.6 mgH2O/l and 28.1 +/- 0.8 mgH2O/l, [P
      < 0.05]) than did Hygroster (airway temperature: 28.1 +/- 0.3 degrees C [P <
      0.05]; AH: 27 +/- 1.2 mgH2O/l [P < 0.05]). Both devices suffered a loss of
      efficiency at the highest minute ventilation and tidal volume, and at the lowest
      minute ventilation. Active Performer had higher airway temperature and AH (31.9
      +/- 0.3 degrees C and 34.3 +/- 0.6 mgH2O/l; [P < 0.05]) than did Hygrobac and
      Hygroster, and was not influenced by minute ventilation or tidal volume. In vivo,
      the efficiency of passive Performer was similar to that of Hygrobac but better
      than Hygroster, whereas Active Performer was better than both. The active
      Performer exhibited good efficiency when used for up to 12 hours in vivo.
      CONCLUSION: This study showed that active Performer may provide adequate
      conditioning of inspired gases, both as a passive and as an active device.

PMID- 15469570
TI  - Case report: a ball valve blood clot in the airways - life-saving whole tube
      suction.
AB  - Respiratory tract obstruction due to a blood clot may result in life threatening
      ventilatory impairment. Ball valve blood clot obstructions of the airways are
      rare. A ball valve blood clot acts as a one-way valve, allowing (near) normal air
      entry into the airways, but (completely) blocking expiration. In a near fatal
      case of obstruction of the airways by a ball valve blood clot, we performed
      'whole tube suction' to resolve the airway problem.

PMID- 15469571
TI  - Hospitalized cancer patients with severe sepsis: analysis of incidence,
      mortality, and associated costs of care.
AB  - INTRODUCTION: Infection is an important complication in cancer patients, which
      frequently leads to or prolongs hospitalization, and can also lead to acute organ
      dysfunction (severe sepsis) and eventually death. While cancer patients are known
      to be at higher risk for infection and subsequent complications, there is no
      national estimate of the magnitude of this problem. Our objective was to identify
      cancer patients with severe sepsis and to project these numbers to national
      levels. METHODS: Data for all 1999 hospitalizations from six states (Florida,
      Massachusetts, New Jersey, New York, Virginia, and Washington) were merged with
      US Census data, Centers for Disease Control vital statistics and National Cancer
      Institute, Surveillance, Epidemiology, and End Results initiative cancer
      prevalence data. Malignant neoplasms were identified by International
      Classification of Disease (ninth revision, clinical modification) (ICD-9-CM)
      codes (140-208), and infection and acute organ failure were identified from ICD-9
      CM codes following Angus and colleagues. Cases were identified as a function of
      age and were projected to national levels. RESULTS: There were 606,176 cancer
      hospitalizations identified, with severe sepsis present in 29,795 (4.9%).
      Projecting national estimates for the US population, cancer patients account for
      126,209 severe sepsis cases annually, or 16.4 cases per 1000 people with cancer
      per year. The inhospital mortality for cancer patients with severe sepsis was
      37.8%. Compared with the overall population, cancer patients are much more likely
      to be hospitalized (relative risk, 2.77; 95% confidence interval, 2.77-2.78) and
      to be hospitalized with severe sepsis (relative risk, 3.96; 95% confidence
      interval, 3.94-3.99). Overall, severe sepsis is associated with 8.5% (46,729) of
      all cancer deaths at a cost of 3.4 billion dollars per year. CONCLUSION: Severe
      sepsis is a common, deadly, and costly complication in cancer patients.

PMID- 15469572
TI  - Comparison of two percutaneous tracheostomy techniques, guide wire dilating
      forceps and Ciaglia Blue Rhino: a sequential cohort study.
AB  - INTRODUCTION: To evaluate and compare the peri-operative and postoperative
      complications of the two most frequently used percutaneous tracheostomy
      techniques, namely guide wire dilating forceps (GWDF) and Ciaglia Blue Rhino
      (CBR). METHODS: A sequential cohort study with comparison of short-term and long
      term peri-operative and postoperative complications was performed in the
      intensive care unit of the University Medical Centre in Nijmegen, The
      Netherlands. In the period 1997-2000, 171 patients underwent a tracheostomy with
      the GWDF technique and, in the period 2000-2003, a further 171 patients with the
      CBR technique. All complications were prospectively registered on a standard
      form. RESULTS: There was no significant difference in major complications, either
      peri-operative or postoperative. We found a significant difference in minor peri
      operative complications (P < 0.01) and minor late complications (P < 0.05).
      CONCLUSION: Despite a difference in minor complications between GWDF and CBR,
      both techniques seem equally reliable.

PMID- 15469573
TI  - Effects of positive end-expiratory pressure on gastric mucosal perfusion in acute
      respiratory distress syndrome.
AB  - INTRODUCTION: Positive end-expiratory pressure (PEEP) improves oxygenation and
      can prevent ventilator-induced lung injury in patients with acute respiratory
      distress syndrome (ARDS). Nevertheless, PEEP can also induce detrimental effects
      by its influence on the cardiovascular system. The purpose of this study was to
      assess the effects of PEEP on gastric mucosal perfusion while applying a
      protective ventilatory strategy in patients with ARDS. METHODS: Eight patients
      were included. A pressure-volume curve was traced and ideal PEEP, defined as
      lower inflection point + 2 cmH2O, was determined. Gastric tonometry was measured
      continuously (Tonocap). After baseline measurements, 10, 15 and 20 cmH2O PEEP and
      ideal PEEP were applied for 30 min each. By the end of each period, hemodynamic,
      CO2 gap (gastric minus arterial partial pressures), and ventilatory measurements
      were performed. RESULTS: PEEP had no effect on CO2 gap (median [range], baseline:
      19 [2-30] mmHg; PEEP 10: 19 [0-40] mmHg; PEEP 15: 18 [0-39] mmHg; PEEP 20: 17 [4
      39] mmHg; ideal PEEP: 19 [9-39] mmHg; P = 0.18). Cardiac index also remained
      unchanged (baseline: 4.6 [2.5-6.3] l min(-1) m(-2); PEEP 10: 4.5 [2.5-6.9] l min(
      1) m(-2); PEEP 15: 4.3 [2-6.8] l min(-1) m(-2); PEEP 20: 4.7 [2.4-6.2] l min(-1)
      m(-2); ideal PEEP: 5.1 [2.1-6.3] l min(-1) m(-2); P = 0.08). One patient did not
      complete the protocol because of hypotension. CONCLUSION: PEEP of 10-20 cmH2O
      does not affect gastric mucosal perfusion and is hemodynamically well tolerated
      in most patients with ARDS, including those receiving adrenergic drugs.

PMID- 15469574
TI  - Altered immune parameters in chronic alcoholic patients at the onset of infection
      and of septic shock.
AB  - INTRODUCTION: Chronic alcoholic patients have a threefold to fourfold increased
      risk for developing a severe infection or septic shock after surgery, which might
      be due to altered immune response. The aim of this outcome matched study was to
      investigate proinflammatory and anti-inflammatory immune parameters during the
      course of infection and subsequent septic shock in chronic alcoholic patients,
      and to compare these parameters with those in nonalcoholic patients. METHODS:
      Twenty-eight patients from a cohort of fifty-six with either pneumonia or
      peritonitis and subsequent septic shock were selected. Fourteen patients were
      chronic alcoholics whereas fourteen were nonalcoholic patients. Chronic alcoholic
      patients met criteria (Diagnostic and Statistical Manual of Mental Disorders IV,
      of the American Psychiatric Association) for alcohol abuse or dependence.
      Measurements were performed during the onset of infection (within 24 hours after
      the onset of infection), in early septic shock (within 12 hours after onset of
      septic shock) and in late septic shock (72 hours after the onset). Blood
      measurements included proinflammatory and anti-inflammatory cytokines. RESULTS:
      Chronic alcoholic patients exhibited significantly lower plasma levels of IL-8 (P
      < 0.010) during the onset of infection than did matched nonalcoholic patients. In
      early septic shock, chronic alcoholic patients had significantly decreased levels
      of IL-1beta (P < 0.015), IL-6 (P < 0.016) and IL-8 (P < 0.010). The anti
      inflammatory parameters IL-10 and tumour necrosis factor receptors I and II did
      not differ between alcoholic and nonalcoholic patients. CONCLUSION: At the onset
      of infection and during early septic shock, chronic alcoholic patients had lower
      levels of proinflammatory immune parameters than did nonalcoholic patients.
      Therefore, immunomodulatory therapy administered early may be considered in
      chronic alcoholic patients at the onset of an infection because of their altered
      proinflammatory immune response.

PMID- 15469575
TI  - The outcome of extubation failure in a community hospital intensive care unit: a
      cohort study.
AB  - INTRODUCTION: Extubation failure has been associated with poor intensive care
      unit (ICU) and hospital outcomes in tertiary care medical centers. Given the
      large proportion of critical care delivered in the community setting, our purpose
      was to determine the impact of extubation failure on patient outcomes in a
      community hospital ICU. METHODS: A retrospective cohort study was performed using
      data gathered in a 16-bed medical/surgical ICU in a community hospital. During 30
      months, all patients with acute respiratory failure admitted to the ICU were
      included in the source population if they were mechanically ventilated by
      endotracheal tube for more than 12 hours. Extubation failure was defined as
      reinstitution of mechanical ventilation within 72 hours (n = 60), and the control
      cohort included patients who were successfully extubated at 72 hours (n = 93).
      RESULTS: The primary outcome was total ICU length of stay after the initial
      extubation. Secondary outcomes were total hospital length of stay after the
      initial extubation, ICU mortality, hospital mortality, and total hospital cost.
      Patient groups were similar in terms of age, sex, and severity of illness, as
      assessed using admission Acute Physiology and Chronic Health Evaluation II score
      (P > 0.05). Both ICU (1.0 versus 10 days; P < 0.01) and hospital length of stay
      (6.0 versus 17 days; P < 0.01) after initial extubation were significantly longer
      in reintubated patients. ICU mortality was significantly higher in patients who
      failed extubation (odds ratio = 12.2, 95% confidence interval [CI] = 1.5-101; P <
      0.05), but there was no significant difference in hospital mortality (odds ratio
      = 2.1, 95% CI = 0.8-5.4; P < 0.15). Total hospital costs (estimated from direct
      and indirect charges) were significantly increased by a mean of 33,926 US dollars
      (95% CI = 22,573 US dollars - 45,280 US dollars; P < 0.01). CONCLUSION:
      Extubation failure in a community hospital is univariately associated with
      prolonged inpatient care and significantly increased cost. Corroborating data
      from tertiary care centers, these adverse outcomes highlight the importance of
      accurate predictors of extubation outcome.

PMID- 15469576
TI  - Erythropoietin and renin as biological markers in critically ill patients.
AB  - INTRODUCTION: During sepsis the endocrine, immune and nervous systems elaborate a
      multitude of biological responses. Little is known regarding the mechanisms
      responsible for the final circulating erythropoietin (EPO) and renin levels in
      septic shock. The aim of the present study was to assess the role of EPO and
      renin as biological markers in patients with septic shock. METHODS: A total of 44
      critically ill patients with septic shock were evaluated. RESULTS: Nonsurvivors
      had significantly higher serum EPO levels than did survivors on admission (median
      [minimum-maximum]; 61 [10-602] versus 20 [5-369]). A negative relationship
      between serum EPO and blood haemoglobin concentrations was observed in the
      survivor group (r = -0.61; P < 0.001). In contrast, in the nonsurvivors the serum
      EPO concentration was independent of the blood haemoglobin concentration.
      Furthermore, we observed significant relationships between EPO concentration and
      lactate (r = 0.5; P < 0.001), arterial oxygen tension/fractional inspired oxygen
      ratio (r = -0.41; P < 0.005), arterial pH (r = -0.58; P < 0.001) and renin
      concentration (r = 0.42; P < 0.005). With regard to renin concentration,
      significant correlations with lactate (r = 0.52; P < 0.001) and arterial pH (r = 
      0.33; P < 0.05) were observed. CONCLUSION: Our findings show that EPO and renin
      concentrations increased in patients admitted to the intensive care unit with
      septic shock. Renin may be a significant mediator of EPO upregulation in patients
      with septic shock. Further studies regarding the regulation of EPO expression are
      clearly warranted.

PMID- 15469577
TI  - Critical care procedure logging using handheld computers.
AB  - INTRODUCTION: We conducted this study to evaluate the feasibility of implementing
      an internet-linked handheld computer procedure logging system in a critical care
      training program. METHODS: Subspecialty trainees in the Interdepartmental
      Division of Critical Care at the University of Toronto received and were trained
      in the use of Palm handheld computers loaded with a customized program for
      logging critical care procedures. The procedures were entered into the handheld
      device using checkboxes and drop-down lists, and data were uploaded to a central
      database via the internet. To evaluate the feasibility of this system, we tracked
      the utilization of this data collection system. Benefits and disadvantages were
      assessed through surveys. RESULTS: All 11 trainees successfully uploaded data to
      the central database, but only six (55%) continued to upload data on a regular
      basis. The most common reason cited for not using the system pertained to initial
      technical problems with data uploading. From 1 July 2002 to 30 June 2003, a total
      of 914 procedures were logged. Significant variability was noted in the number of
      procedures logged by individual trainees (range 13-242). The database generated
      by regular users provided potentially useful information to the training program
      director regarding the scope and location of procedural training among the
      different rotations and hospitals. CONCLUSION: A handheld computer procedure
      logging system can be effectively used in a critical care training program.
      However, user acceptance was not uniform, and continued training and support are
      required to increase user acceptance. Such a procedure database may provide
      valuable information that may be used to optimize trainees' educational
      experience and to document clinical training experience for licensing and
      accreditation.

PMID- 15469579
TI  - Early tracheostomy in intensive care trauma patients improves resource
      utilization: a cohort study and literature review.
AB  - INTRODUCTION: Despite the integral role played by tracheostomy in the management
      of trauma patients admitted to intensive care units (ICUs), its timing remains
      subject to considerable practice variation. The purpose of this study is to
      examine the impact of early tracheostomy on the duration of mechanical
      ventilation, ICU length of stay, and outcomes in trauma ICU patients. METHODS:
      The following data were obtained from a prospective ICU database containing
      information on all trauma patients who received tracheostomy over a 5-year
      period: demographics, Acute Physiology and Chronic Health Evaluation II score,
      Simplified Acute Physiology Score II, Glasgow Coma Scale score, Injury Severity
      Score, type of injuries, ICU and hospital outcomes, ICU and hospital length of
      stay (LOS), and the type of tracheostomy procedure (percutaneous versus
      surgical). Tracheostomy was considered early if it was performed by day 7 of
      mechanical ventilation. We compared the duration of mechanical ventilation, ICU
      LOS and outcome between early and late tracheostomy patients. Multivariate
      analysis was performed to assess the impact of tracheostomy timing on ICU stay.
      RESULTS: Of 653 trauma ICU patients, 136 (21%) required tracheostomies, 29 of
      whom were early and 107 were late. Age, sex, Acute Physiology and Chronic Health
      Evaluation II score, Simplified Acute Physiology Score II and Injury Severity
      Score were not different between the two groups. Patients with early tracheostomy
      were more likely to have maxillofacial injuries and to have lower Glasgow Coma
      Scale score. Duration of mechanical ventilation was significantly shorter with
      early tracheostomy (mean +/- standard error: 9.6 +/- 1.2 days versus 18.7 +/- 1.3
      days; P < 0.0001). Similarly, ICU LOS was significantly shorter (10.9 +/- 1.2
      days versus 21.0 +/- 1.3 days; P < 0.0001). Following tracheostomy, patients were
      discharged from the ICU after comparable periods in both groups (4.9 +/- 1.2 days
      versus 4.9 +/- 1.1 days; not significant). ICU and hospital mortality rates were
      similar. Using multivariate analysis, late tracheostomy was an independent
      predictor of prolonged ICU stay (>14 days). CONCLUSION: Early tracheostomy in
      trauma ICU patients is associated with shorter duration of mechanical ventilation
      and ICU LOS, without affecting ICU or hospital outcome. Adopting a standardized
      strategy of early tracheostomy in appropriately selected patients may help in
      reducing unnecessary resource utilization.

PMID- 15469578
TI  - Novel applications of therapeutic hypothermia: report of three cases.
AB  - Therapeutic hypothermia can provide neuroprotection in various situations where
      global or focal neurological injury has occurred. Hypothermia has been shown to
      be effective in a large number of animal experiments. In clinical trials,
      hypothermia has been used in patients with postanoxic injury following
      cardiopulmonary resuscitation, in traumatic brain injury with high intracranial
      pressure, in the perioperative setting during various surgical procedures and for
      various other indications. There is thus evidence that hypothermia can be
      effective in various situations of neurological injury, although a number of
      questions remain unanswered. We describe three patients with unusual causes of
      neurological injury, whose clinical situation was in fundamental aspects
      analogous to conditions where hypothermia has been shown to be effective.

PMID- 15469580
TI  - Mild hypothermia after near drowning in twin toddlers.
AB  - INTRODUCTION: We report a case of twin toddlers who both suffered near drowning
      but with different post-trauma treatment and course, and different neurological
      outcomes. METHODS AND RESULTS: Two twin toddlers (a boy and girl, aged 2 years
      and 3 months) suffered hypothermic near drowning with protracted cardiac arrest
      and aspiration. The girl was treated with mild hypothermia for 72 hours and
      developed acute respiratory dysfunction syndrome and sepsis. She recovered
      without neurological deficit. The boy's treatment was conducted under
      normothermia without further complications. He developed an apallic syndrome.
      CONCLUSION: Although the twin toddlers experienced the same near drowning
      accident together, the outcomes with respect to neurological status and
      postinjury complications were completely different. One of the factors that
      possibly influenced the different postinjury course might have been prolonged
      mild hypothermia.

PMID- 15469582
TI  - Albumin in critical care: SAFE, but worth its salt?
AB  - Intravascular fluid therapy is a common critical care intervention. However, the
      optimal type of resuscitation fluid, crystalloid or colloid, remains
      controversial. Despite the many theoretical benefits of human albumin
      administration in critically ill patients, there has been little evidence to
      support its widespread clinical use. Previous systematic reviews have led to
      conflicting results regarding the safety and efficacy of albumin. The recently
      reported Saline versus Albumin Evaluation study has provided conclusive evidence
      that 4% albumin is as safe as saline for resuscitation, although no overall
      benefit of albumin use was seen. Subgroup analysis of the albumin-treated group
      revealed a trend towards decreased mortality in patients with septic shock, and a
      trend towards increased mortality in trauma patients, especially those with
      traumatic brain injury. The results of these subgroups, as well as the use of
      higher albumin concentrations and other synthetic colloids (dextrans, starches),
      require rigorous evaluation in clinical trials. Finally, the Saline versus
      Albumin Evaluation trial represents a methodological milestone in critical care
      medicine, due to its size, its efficient trial design, and its logistical
      coordination. Future studies are still required, however, to establish a
      therapeutic niche for albumin and other colloids.

PMID- 15469581
TI  - Clinical review: moral assumptions and the process of organ donation in the
      intensive care unit.
AB  - The objective of the present article is to review moral assumptions underlying
      organ donation in the intensive care unit. Data sources used include personal
      experience, and a Medline search and a non-Medline search of relevant English
      language literature. The study selection included articles concerning organ
      donation. All data were extracted and analysed by the author. In terms of data
      synthesis, a rational, utilitarian moral perspective dominates, and has captured
      and circumscribed, the language and discourse of organ donation. Examples include
      "the problem is organ shortage", "moral or social duty or responsibility to
      donate", "moral responsibility to advocate for donation", "requesting organs" or
      "asking for organs", "trained requesters", "pro-donation support persons",
      "persuasion" and defining "maximising donor numbers" as the objective while
      impugning the moral validity of nonrational family objections to organ donation.
      Organ donation has recently been described by intensivists in a morally neutral
      way as an "option" that they should "offer", as "part of good end-of-life care",
      to families of appropriate patients. In conclusion, the review shows that a
      rational utilitarian framework does not adequately encompass interpersonal
      interactions during organ donation. A morally neutral position frees intensivists
      to ensure that clinical and interpersonal processes in organ donation are
      performed to exemplary standards, and should more robustly reflect societal
      acceptability of organ donation (although it may or may not "produce more
      donors").

PMID- 15469583
TI  - Why can't I visit? The ethics of visitation restrictions - lessons learned from
      SARS.
AB  - Patients want, need and expect that their relatives will be able to visit them
      during inpatient admissions or accompany them during ambulatory visits. The
      sudden outbreak of severe acute respiratory syndrome (SARS), or a similar
      contagious pathogen, will restrict the number of people entering the hospital.
      The ethical values that underlie visitor restrictions are discussed here.

PMID- 15469585
TI  - Role of iron in anaemic critically ill patients: it's time to investigate!
AB  - Anaemia is a common problem in critically ill patients admitted to intensive care
      units. Many factors can be involved in its development, including rapid
      alterations of iron metabolism. Maintenance of iron homeostasis is a prerequisite
      for many essential biological processes and a central element for the development
      of erythroid precursors and mature red blood cells. With the inflammatory
      process, iron distribution is disturbed, with decreased serum iron levels and
      increased iron stores. Little information is available on the precise role of
      alterations of iron metabolism in the development of iron anaemia in critically
      ill patients.

PMID- 15469586
TI  - Positive end-expiratory pressure in acute respiratory distress syndrome - an old
      yet mysterious tool.
AB  - A recent study by Bruhn and colleagues, discussed here, confirms that even high
      levels of positive end-expiratory pressure (PEEP) - up to 20 cmH2O - may be
      applied in conditions of moderate acute respiratory distress syndrome. Such
      levels of PEEP were found to be safe in terms of their impact on cardiac output
      and adequacy of gastric mucosal perfusion once systemic haemodynamics were
      stabilized by adequate fluid replacement and catecholamine therapy. However, we
      strongly recommend that the reader does not oversimplify the conclusions of that
      study. PEEP therapy is not inherently safe with respect to haemodynamics and
      regional organ perfusion, but it may be used safely, even at high levels of up to
      20 cmH2O, if haemodynamic therapy is appropriate.

PMID- 15469587
TI  - Extubation failure: an outcome to be avoided.
AB  - Extubation failure is an outcome of increasing importance but nearly all studies
      have been conducted in academic settings. The article by Seymour and colleagues
      demonstrates that extubation failure is an outcome to be avoided in the community
      hospital setting as well. Patients failing extubation experience longer lengths
      of stay, experience higher intensive care unit mortality, and incur greater
      hospital costs. Investigators have identified tools for predicting extubated
      patients at highest risk for reintubation. The predictors focus on detecting
      upper airway obstruction, inadequate cough, excess respiratory secretions, and
      abnormal mental status. Systematic application of these predictors has the
      potential to improve outcome.

PMID- 15469588
TI  - Reluctant horses at the digital river.
AB  - Mastery of the changing bank of information needed to practice at the cutting
      edge will require the exploitation of emerging informatics and communication
      technologies. Whether their limitless promise will be embraced or forgone will
      depend as much on human as on technological practice.

PMID- 15469589
TI  - Saline volume expansion and cardiovascular physiology: novel observations, old
      explanations, and new questions.
AB  - In a clinical investigation, Kumar and coworkers reported the hemodynamic events
      that accompany plasma volume expansion over 3 hours in healthy adult volunteers,
      and found that increases in stroke volume (SV) may be related to increases in
      left ventricular (LV)/right ventricular (RV) end-diastolic volume, as they
      expected, but also to decreases in LV/RV end-systolic volume. The latter finding
      suggests increased contractility and/or decreased afterload, which do not fit
      with their perception that clinicians ascribe increases in SV to increases in end
      diastolic volume based on Starling's work. Increased ejection fraction and
      decreased vascular resistances were also observed. The same authors recently
      reported novel data suggesting that reduced blood viscosity may account for the
      observed reduction in vascular resistances with saline volume expansion. However,
      the variances in preload and afterload, along with uncertainty in estimates of
      contractility, substantially limit their ability to define a primary mechanism to
      explain decreases in LV end-systolic volume. A focus on using ejection fraction
      to evaluate the integrated performance of the cardiovascular system is provided
      to broaden this analytic perspective. Sagawa and colleagues described an approach
      to estimate the relationship, under clinical conditions, between ventricular and
      arterial bed elastances (i.e. maximal ventricular systolic elastance [Emax] and
      maximal arterial systolic elastance [Ea]), reflecting ventricular-arterial
      coupling. I used the mean data provided in one of the reports from Kumar and
      coworkers to calculate that LV Emax decreased from 1.09 to 0.96 mmHg/ml with
      saline volume expansion, while Ea decreased from 1.1 to 0.97 mmHg/ml and the SV
      increased (i.e. the increase in mean SV was associated with a decrease in mean
      afterload while the mean contractility decreased). The results reported by Kumar
      and coworkers invite further studies in normal and critically ill patients during
      acute saline-induced plasma volume expansion and hemodilution. If reduced
      viscosity decreases afterload, then this raises the questions by what mechanism,
      and what is the balance of benefit and harm associated with reduced blood
      viscosity affecting oxygen delivery? Why the mean Emax might decrease must be
      evaluated with respect to benefit in reducing ventricular work or a negative
      inotropic effect of saline.

PMID- 15469590
TI  - Percutaneous dilatation tracheostomy: which technique is the best for the
      critically ill patient, and how can we gather further scientific evidence?
AB  - Percutaneous dilatation tracheostomy in the intensive care setting presents an
      increasingly important concept for establishing a large-bore tracheal airway with
      minimal surgical intervention. Over the last years, different technical solutions
      have been studied to assess their respective risks and benefits to determine
      whether one method is actually superior. A recent observational study comparing
      two such techniques prompted this commentary, which reviews the current
      literature, comments on study design and suggests interesting topics for future
      research in this field.

PMID- 15469591
TI  - Tracheostomy must be individualized!
AB  - Tracheostomy is one of the most frequent procedures carried out in critically ill
      patients with major advantages compared to translaryngeal endotracheal intubation
      such as reduced laryngeal anatomical alterations, reduced inspiratory load,
      better patient's tolerance and nursing. Thus, tracheostomy can enhance patient's
      care in patients who need prolonged mechanical ventilation and/or control of
      airways. The right timing of tracheostomy remains controversial, however it
      appears that early tracheostomy in selected severe trauma, burn and neurological
      patients could be effective to reduce the duration of mechanical ventilation
      intensive care stay and costs. Percutaneous tracheostomy techniques are becoming
      the procedure of choice in the majority of the cases, since they are safe, easy
      and quick, and complications are minor. However, percutaneous tracheostomies
      should be always performed by experienced physicians to avoid unnecessary
      additional complications. It is not clear the superiority of one percutaneous
      technique compared to another, but experience of the operator and clinical
      individual anatomical, physiopathological characteristics of the patient should
      be always considered. We believe that the operator should have experience of at
      least one intrusive and one extrusive percutaneous technique. The general
      "optimal" tracheostomy technique and timing do not exist, but tracheostomy should
      be targeted on the patient's individual clinical characteristics.

PMID- 15469592
TI  - Erythropoietin in the critically ill - is it more than just blood?
AB  - Erythropoietin (EPO) has been in clinical use for the treatment of anemia for
      over 15 years. Recently it has been demonstrated that EPO has actions other than
      stimulating the bone marrow. It has been suggested that due to its tissue
      protecting effect, EPO may be effective in improving outcome in the critically
      ill.

PMID- 15469593
TI  - Pro/con clinical debate: tracheostomy is ideal for withdrawal of mechanical
      ventilation in severe neurological impairment.
AB  - Most clinical trials on the topic of extubation have involved patients outside
      the neurological intensive care unit. As a result, in this area clinicians are
      left with little evidence on which to base their decision making. Although
      tracheostomies are increasingly common procedures, they are not without
      complications and costs, and hence a decision to perform them should not be taken
      lightly. In this issue of Critical Care two groups debate the merits of
      tracheostomy before extubation in a patient with neurological impairment. What
      becomes very clear is the need for more high quality data for this common
      clinical problem.

PMID- 15469594
TI  - Science review: extracellular acidosis and the immune response: clinical and
      physiologic implications.
AB  - Metabolic acidosis is among the most common abnormalities seen in patients
      suffering from critical illness. Its etiologies are multiple and treatment of the
      underlying condition is the mainstay of therapy. However, growing evidence
      suggests that acidosis itself has profound effects on the host, particularly in
      the area of immune function. Given the central importance of immune function to
      the outcome of critical illness, there is renewed interest in elucidating the
      effects of this all too common condition on the immune response. In this review
      we concentrate on the effects of extracellular acids on production and release of
      inflammatory mediators, and we demonstrate that different acids produce different
      effects despite similar extracellular pH. Finally, we discuss potential clinical
      implications.

PMID- 15469595
TI  - Science review: recombinant human erythropoietin in critical illness: a role
      beyond anemia?
AB  - Erythropoiesis usually fails during severe illness because of a blunting of the
      kidney-erythropoietin (EPO)-bone marrow axis. In this setting, clinical studies
      have shown that recombinant human erythropoietin (rhEPO), administered in
      pharmacological amounts, significantly reduces the need for blood transfusions.
      In addition to the kidney, however, EPO is also produced locally by other tissues
      in a paracrine-autocrine manner. Here, similar to its role in the bone marrow,
      EPO rescues cells from apoptosis. Additionally, EPO reduces inflammatory
      responses, restores vascular autoregulation, and promotes healing. The results of
      many studies (including a phase II clinical trial in ischemic stroke) demonstrate
      that rhEPO protects the brain, spinal cord, retina, heart, and kidney from
      ischemic and other types of injury. Although rhEPO is efficacious in the
      treatment of EPO-deficient anemia during illness, inadequate effort has been
      devoted to determining whether direct tissue protection might also result from
      its administration. Here, we speculate on the potential utility of EPO as a
      protective cytokine in the context of acute critical illness and suggest key
      parameters required for a proof-of-concept clinical study.

PMID- 15469597
TI  - Bench-to-bedside review: chest wall elastance in acute lung injury/acute
      respiratory distress syndrome patients.
AB  - The importance of chest wall elastance in characterizing acute lung injury/acute
      respiratory distress syndrome patients and in setting mechanical ventilation is
      increasingly recognized. Nearly 30% of patients admitted to a general intensive
      care unit have an abnormal high intra-abdominal pressure (due to ascites, bowel
      edema, ileus), which leads to an increase in the chest wall elastance. At a given
      applied airway pressure, the pleural pressure increases according to (in the
      static condition) the equation: pleural pressure = airway pressure x (chest wall
      elastance/total respiratory system elastance). Consequently, for a given applied
      pressure, the increase in pleural pressure implies a decrease in transpulmonary
      pressure (airway pressure - pleural pressure), which is the distending force of
      the lung, implies a decrease of the strain and of ventilator-induced lung injury,
      implies the need to use a higher airway pressure during the recruitment maneuvers
      to reach a sufficient transpulmonary opening pressure, implies hemodynamic risk
      due to the reductions in venous return and heart size, and implies a possible
      increase of lung edema, partially due to the reduced edema clearance. It is
      always important in the most critically ill patients to assess the intra
      abdominal pressure and the chest wall elastance.

PMID- 15469596
TI  - Science review: natriuretic peptides in critical illness.
AB  - The present review will cover the mechanisms of release and the potential
      pathophysiological role of different natriuretic peptides in critically ill
      patients. By focusing on the cardiovascular system, possible implications of
      natriuretic peptides for diagnosis and treatment will be presented. In critical
      illness such as sepsis, trauma or major surgery, systemic hypotension and an
      intrinsic myocardial dysfunction occur. Impairment of the cardiovascular system
      contributes to poor prognosis in severe human sepsis. Natriuretic peptides have
      emerged as valuable marker substances to detect left ventricular dysfunction in
      congestive heart failure of different origins. Increased plasma levels of
      circulating natriuretic peptides, atrial natriuretic peptide, N-terminal pro
      atrial natriuretic peptide, brain natriuretic peptide and its N-terminal moiety N
      terminal pro-brain natriuretic peptide have also been found in critically ill
      patients. All of these peptides have been reported to reflect left ventricular
      dysfunction in these patients. The increased wall stress of the cardiac atria and
      ventricles is followed by the release of these natriuretic peptides. Furthermore,
      the release of atrial natriuretic peptide and brain natriuretic peptide might be
      triggered by members of the IL-6-related family and endotoxin in the critically
      ill. Apart from the vasoactive actions of circulating natriuretic peptides and
      their broad effects on the renal system, anti-ischemic properties and
      immunological functions have been reported for atrial natriuretic peptide. The
      early onset and rapid reversibility of left ventricular impairment in patients
      with good prognosis associated with a remarkably augmented plasma concentration
      of circulating natriuretic peptides suggest a possible role of these hormones in
      the monitoring of therapy success and the estimation of prognosis in the
      critically ill.

PMID- 15469598
TI  - Bench-to-bedside review: iron metabolism in critically ill patients.
AB  - Critically ill patients frequently develop anemia due to several factors. Iron
      withholding mechanisms caused by inflammation contribute to this anemia. The iron
      metabolism imbalances described or reported in all intensive care studies are
      similar to the values observed in anemia of inflammation. The administration of
      iron could be useful in the optimization of recombinant human erythropoietin
      activity, but this could be at the expense of bacterial proliferation. Since
      there is a lack of evidence to support either oral or intravenous iron
      administration in intensive care patients, further studies are necessary to
      determine the efficacy and safety of iron supplementation in conjunction with
      recombinant human erythropoietin in critically ill patients. We review the
      mechanisms leading to iron sequestration in the presence of inflammation. The
      present article also reviews the literature describing the iron status in
      critically ill patients and explores the role of iron supplementation in this
      setting.

PMID- 15469599
TI  - Bench-to-bedside review: microdialysis in intensive care medicine.
AB  - Microdialysis is a technique used to measure the concentrations of various
      compounds in the extracellular fluid of an organ or in a body fluid. It is a form
      of metabolic monitoring that provides real-time, continuous information on
      pathophysiological processes in target organs. It was introduced in the early
      1970s, mainly to measure concentrations of neurotransmitters in animal
      experiments and clinical settings. Using commercial equipment it is now possible
      to conduct analyses at the bedside by collecting interstitial fluid for
      measurement of carbohydrate and lipid metabolites. Important research has been
      reported in the field of neurosurgery in recent decades, but use of metabolic
      monitoring in critical care medicine is not yet routine. The present review
      provides an overview of findings from clinical studies using microdialysis in
      critical care medicine, focusing on possible indications for clinical biochemical
      monitoring. An important message from the review is that sequential and tissue
      specific metabolic monitoring, in vivo, is now available.

PMID- 15469600
TI  - Clinical review: how to identify high-risk surgical patients.
AB  - Postoperative outcome is mainly influenced by ventricular function. Tests
      designed to identify myocardial ischemia alone will fail to detect cardiac
      failure and are thus inadequate as a screening test for identification of cardiac
      risk in noncardiac surgical patients. We find that the degree of cardiac failure
      is the most important predictor of morbidity and mortality. We use
      cardiopulmonary exercise testing to establish the anaerobic threshold as the sole
      measure of cardiopulmonary function as well as to detect myocardial ischemia.
      Patients with an anaerobic threshold < 11 ml/min/kg are at risk for major
      surgery, and perioperative management must be planned accordingly. Myocardial
      ischemia combined with moderate to severe cardiac failure (anaerobic threshold <
      11 ml/min/kg) is predictive of the highest morbidity and mortality.

PMID- 15469601
TI  - Clinical review: hemorrhagic shock.
AB  - This review addresses the pathophysiology and treatment of hemorrhagic shock - a
      condition produced by rapid and significant loss of intravascular volume, which
      may lead sequentially to hemodynamic instability, decreases in oxygen delivery,
      decreased tissue perfusion, cellular hypoxia, organ damage, and death.
      Hemorrhagic shock can be rapidly fatal. The primary goals are to stop the
      bleeding and to restore circulating blood volume. Resuscitation may well depend
      on the estimated severity of hemorrhage. It now appears that patients with
      moderate hypotension from bleeding may benefit by delaying massive fluid
      resuscitation until they reach a definitive care facility. On the other hand, the
      use of intravenous fluids, crystalloids or colloids, and blood products can be
      life saving in those patients who are in severe hemorrhagic shock. The optimal
      method of resuscitation has not been clearly established. A hemoglobin level of 7
      8 g/dl appears to be an appropriate threshold for transfusion in critically ill
      patients with no evidence of tissue hypoxia. However, maintaining a higher
      hemoglobin level of 10 g/dl is a reasonable goal in actively bleeding patients,
      the elderly, or individuals who are at risk for myocardial infarction. Moreover,
      hemoglobin concentration should not be the only therapeutic guide in actively
      bleeding patients. Instead, therapy should be aimed at restoring intravascular
      volume and adequate hemodynamic parameters.

PMID- 15469602
TI  - Statistics review 12: survival analysis.
AB  - This review introduces methods of analyzing data arising from studies where the
      response variable is the length of time taken to reach a certain end-point, often
      death. The Kaplan-Meier methods, log rank test and Cox's proportional hazards
      model are described.

PMID- 15469603
TI  - Hemorrhagic shock: a review.

PMID- 15469604
TI  - Complications of percutaneous dilating tracheostomy.

PMID- 15469605
TI  - Molecular regulation of pancreatic stellate cell function.
AB  - Until now, no specific therapies are available to inhibit pancreatic fibrosis, a
      constant pathological feature of chronic pancreatitis and pancreatic cancer. One
      major reason is the incomplete knowledge of the molecular principles underlying
      fibrogenesis in the pancreas. In the past few years, evidence has been
      accumulated that activated pancreatic stellate cells (PSCs) are the predominant
      source of extracellular matrix (ECM) proteins in the diseased organ. PSCs are
      vitamin A-storing, fibroblast-like cells with close morphological and biochemical
      similarities to hepatic stellate cells (also known as Ito-cells). In response to
      profibrogenic mediators such as various cytokines, PSCs undergo an activation
      process that involves proliferation, exhibition of a myofibroblastic phenotype
      and enhanced production of ECM proteins. The intracellular mediators of
      activation signals, and their antagonists, are only partially known so far.
      Recent data suggest an important role of enzymes of the mitogen-activated protein
      kinase family in PSC activation. On the other hand, ligands of the nuclear
      receptor PPARgamma (peroxisome proliferator-activated receptor gamma) stimulate
      maintenance of a quiescent PSC phenotype. In the future, targeting regulators of
      the PSC activation process might become a promising approach for the treatment of
      pancreatic fibrosis.

PMID- 15469606
TI  - Genetic alterations and in vivo tumorigenicity of neurospheres derived from an
      adult glioblastoma.
AB  - Pediatric brain tumors may originate from cells endowed with neural
      stem/precursor cell properties, growing in vitro as neurospheres. We have found
      that these cells can also be present in adult brain tumors and form highly
      infiltrating gliomas in the brain of immunodeficient mice. Neurospheres were
      grown from three adult brain tumors and two pediatric gliomas. Differentiation of
      the neurospheres from one adult glioblastoma decreased nestin expression and
      increased that of glial and neuronal markers. Loss of heterozygosity of 10q and
      9p was present in the original glioblastoma, in the neurospheres and in tumors
      grown into mice, suggesting that PTEN and CDKN2A alterations are key genetic
      events in tumor initiating cells with neural precursor properties.

PMID- 15469607
TI  - Evaluation of sense-strand mRNA amplification by comparative quantitative PCR.
AB  - BACKGROUND: RNA amplification is required for incorporating laser-capture
      microdissection techniques into microarray assays. However, standard
      oligonucleotide microarrays contain sense-strand probes, so traditional T7
      amplification schemes producing anti-sense RNA are not appropriate for
      hybridization when combined with conventional reverse transcription labeling
      methods. We wished to assess the accuracy of a new sense-strand RNA amplification
      method by comparing ratios between two samples using quantitative real-time PCR
      (qPCR), mimicking a two-color microarray assay. RESULTS: We performed our
      validation using qPCR. Three samples of rat brain RNA and three samples of rat
      liver RNA were amplified using several kits (Ambion messageAmp, NuGen Ovation,
      and several versions of Genisphere SenseAmp). Results were assessed by comparing
      the liver/brain ratio for 192 mRNAs before and after amplification. In general,
      all kits produced strong correlations with unamplified RNAs. The SenseAmp kit
      produced the highest correlation, and was also able to amplify a partially
      degraded sample accurately. CONCLUSION: We have validated an optimized sense
      strand RNA amplification method for use in comparative studies such as two-color
      microarrays.

PMID- 15469608
TI  - Identitag, a relational database for SAGE tag identification and interspecies
      comparison of SAGE libraries.
AB  - BACKGROUND: Serial Analysis of Gene Expression (SAGE) is a method of large-scale
      gene expression analysis that has the potential to generate the full list of
      mRNAs present within a cell population at a given time and their frequency. An
      essential step in SAGE library analysis is the unambiguous assignment of each 14
      bp tag to the transcript from which it was derived. This process, called tag-to
      gene mapping, represents a step that has to be improved in the analysis of SAGE
      libraries. Indeed, the existing web sites providing correspondence between tags
      and transcripts do not concern all species for which numerous EST and cDNA have
      already been sequenced. RESULTS: This is the reason why we designed and
      implemented a freely available tool called Identitag for tag identification that
      can be used in any species for which transcript sequences are available.
      Identitag is based on a relational database structure in order to allow rapid and
      easy storage and updating of data and, most importantly, in order to be able to
      precisely define identification parameters. This structure can be seen like three
      interconnected modules : the first one stores virtual tags extracted from a given
      list of transcript sequences, the second stores experimental tags observed in
      SAGE experiments, and the third allows the annotation of the transcript sequences
      used for virtual tag extraction. It therefore connects an observed tag to a
      virtual tag and to the sequence it comes from, and then to its functional
      annotation when available. Databases made from different species can be connected
      according to orthology relationship thus allowing the comparison of SAGE
      libraries between species. We successfully used Identitag to identify tags from
      our chicken SAGE libraries and for chicken to human SAGE tags interspecies
      comparison. Identitag sources are freely available on http://pbil.univ
      lyon1.fr/software/identitag/ web site. CONCLUSIONS: Identitag is a flexible and
      powerful tool for tag identification in any single species and for interspecies
      comparison of SAGE libraries. It opens the way to comparative transcriptomic
      analysis, an emerging branch of biology.

PMID- 15469609
TI  - Effectiveness of behavioural graded activity compared with physiotherapy
      treatment in chronic neck pain: design of a randomised clinical trial
      [ISRCTN88733332].
AB  - BACKGROUND: Chronic neck pain is a common complaint in the Netherlands with a
      point prevalence of 14.3%. Patients with chronic neck pain are often referred to
      a physiotherapist and, although many treatments are available, it remains unclear
      which type of treatment is to be preferred. The objective of this article is to
      present the design of a randomised clinical trial, Ephysion, which examines the
      clinical and cost effectiveness of behavioural graded activity compared with a
      physiotherapy treatment for patients with chronic non-specific neck pain.
      METHODS: Eligible patients with non-specific neck pain persisting longer than 3
      months will be randomly allocated to either the behavioural graded activity
      programme or to the physiotherapy treatment. The graded activity programme is
      based on an operant approach, which uses a time-contingent method to increase the
      patient's activity level. This treatment is compared with physiotherapy treatment
      using a pain-contingent method. Primary treatment outcome is the patient's global
      perceived effect concerning recovery from the complaint. Global perceived effect
      on daily functioning is also explored as primary outcome to establish the impact
      of treatment on daily activity. Direct and indirect costs will also be assessed.
      Secondary outcomes include the patient's main complaints, pain intensity, medical
      consumption, functional status, quality of life, and psychological variables.
      Recruitment of patients will take place up to the end of the year 2004 and follow
      up measurement will continue until end 2005.

PMID- 15469611
TI  - External metallic circle in hepaticojejunostomy.
AB  - BACKGROUND: Biliary-enteric anastomosis especially Roux-en Y hepaticojejunostomy
      is frequently used for biliary diversion in benign biliary strictures. In this
      study, we present the results of hepaticojejunostomy with external metallic
      circle. METHODS: Hepaticojejunostomy with external metallic circle were performed
      in eight male Sprague-Dawley rats. At the end of the third month, anastomoses
      were analysed for patency and stability of external circles. RESULTS:
      Relaparotomy revealed that all the anastomoses were patent and circles were in
      original places. CONCLUSION: To provide the patency of narrow hepaticojejunostomy
      anastomoses, external metallic circle can be a good alternative to use of
      internal stents in suitable cases.

PMID- 15469610
TI  - An unusual case of chronic meningitis.
AB  - BACKGROUND: Chronic meningitis is defined as symptoms and signs of meningeal
      inflammation and persisting cerebrospinal fluid abnormalities such as elevated
      protein level and pleocytosis for at least one month. CASE PRESENTATION: A 62
      year-old woman, of unremarkable past medical history, was admitted to hospital
      for investigation of a four-week history of vomiting, malaise an associated
      hyponatraemia. She had a low-grade pyrexia with normal inflammatory markers. A CT
      brain was unremarkable and a contrast MRI brain revealed sub-acute infarction of
      the right frontal cortex but with no evidence of meningeal enhancement. Due to
      increasing confusion and patient clinical deterioration a lumbar puncture was
      performed at 17 days post admission. This revealed gram-negative coccobacilli in
      the CSF, which was identified as Neisseria meningitidis group B. The patient made
      a dramatic recovery with high-dose intravenous ceftriaxone antibiotic therapy for
      meningococcal meningitis. CONCLUSIONS: 1) Chronic bacterial meningitis may
      present highly atypically, particularly in the older adult. 2) There may be an
      absent or reduced febrile response, without a rise in inflammatory markers,
      despite a very unwell patient. 3) Early lumbar puncture is to be encouraged as it
      is essential to confirm the diagnosis.4) Despite a delayed diagnosis appropriate
      antibiotic therapy can still lead to a good outcome.

PMID- 15469612
TI  - Overdispersed logistic regression for SAGE: modelling multiple groups and
      covariates.
AB  - BACKGROUND: Two major identifiable sources of variation in data derived from the
      Serial Analysis of Gene Expression (SAGE) are within-library sampling variability
      and between-library heterogeneity within a group. Most published methods for
      identifying differential expression focus on just the sampling variability. In
      recent work, the problem of assessing differential expression between two groups
      of SAGE libraries has been addressed by introducing a beta-binomial hierarchical
      model that explicitly deals with both of the above sources of variation. This
      model leads to a test statistic analogous to a weighted two-sample t-test. When
      the number of groups involved is more than two, however, a more general approach
      is needed. RESULTS: We describe how logistic regression with overdispersion
      supplies this generalization, carrying with it the framework for incorporating
      other covariates into the model as a byproduct. This approach has the advantage
      that logistic regression routines are available in several common statistical
      packages. CONCLUSIONS: The described method provides an easily implemented tool
      for analyzing SAGE data that correctly handles multiple types of variation and
      allows for more flexible modelling.

PMID- 15469613
TI  - In vitro evaluation of the potential role of sulfite radical in morphine
      associated histamine release.
AB  - BACKGROUND: Intravenous morphine use is associated with elevated histamine
      release leading to bronchoconstriction, edema and hemodynamic instability in some
      patients. This study evaluated the possibility that sulfite, which is present as
      a preservative in many morphine preparations, might contribute to histamine
      release in vitro. RESULTS: The human mast cell line, HMC-1, was exposed to
      various morphine concentrations, in the absence of sulfite, under cell culture
      conditions. Clinically attained concentrations of morphine (0.018microg/ml and
      0.45microg/ml) did not cause increased histamine release from mast cells. There
      was a significant increase in histamine release when the morphine concentration
      was increased by 1184-fold (668microg/ml morphine). Histamine release from mast
      cells exposed to morphine and/or sulfite required the presence of prostaglandin H
      synthetase. Histamine release in experiments using sulfite-containing morphine
      solutions was not statistically different from that observed in morphine-only
      solutions. CONCLUSION: Sulfite in sulfite-containing morphine solutions, at
      concentrations seen clinically, is not responsible for histamine release in in
      vitro experiments of the human mast cell line, HMC-1. This does not preclude the
      fact that sulfite may lead to elevation of histamine levels in vivo.

PMID- 15469614
TI  - Identification of hip fracture patients from radiographs using Fourier analysis
      of the trabecular structure: a cross-sectional study.
AB  - BACKGROUND: This study presents an analysis of trabecular bone structure in
      standard radiographs using Fourier transforms and principal components analysis
      (PCA) to identify contributions to hip fracture risk. METHODS: Radiographs were
      obtained from 26 hip fracture patients and 24 controls. They were digitised and
      five regions of interest (ROI) were identified from the femoral head and neck for
      analysis. The power spectrum was obtained from the Fourier transform of each
      region and three profiles were produced; a circular profile and profiles parallel
      and perpendicular to the preferred orientation of the trabeculae. PCA was used to
      generate a score from each profile, which we hypothesised could be used to
      discriminate between the fracture and control groups. The fractal dimension was
      also calculated for comparison. The area under the receiver operating
      characteristic curve (Az) discriminating the hip fracture cases from controls was
      calculated for each analysis. RESULTS: Texture analysis of standard radiographs
      using the fast Fourier transform yielded variables that were significantly
      associated with fracture and not significantly correlated with age, body mass
      index or femoral neck bone mineral density. The anisotropy of the trabecular
      structure was important; both the perpendicular and circular profiles were
      significantly better than the parallel-profile (P < 0.05). No significant
      differences resulted from using the various ROI within the proximal femur. For
      the best three groupings of profile (circular, parallel or perpendicular), method
      (PCA or fractal) and ROI (Az = 0.84 - 0.93), there were no significant
      correlations with femoral neck bone mineral density, age, or body mass index. PCA
      analysis was found to perform better than fractal analysis (P = 0.019).
      CONCLUSIONS: Both PCA and fractal analysis of the FFT data could discriminate
      successfully between the fracture and control groups, although PCA was
      significantly stronger than fractal dimension. This method appears to provide a
      powerful tool for the assessment of bone structure in vivo with advantages over
      standard fractal methods.

PMID- 15469616
TI  - Community nursing needs more silver surfers: a questionnaire survey of primary
      care nurses' use of information technology.
AB  - BACKGROUND: In the UK the health service is investing more than ever before in
      information technology (IT) and primary care nurses will have to work with
      computers. Information about patients will be almost exclusively held in
      electronic patient records; and much of the information about best practice is
      most readily accessible via computer terminals. OBJECTIVE: To examine the
      influence of age and nursing profession on the level of computer use. METHODS: A
      questionnaire was developed to examine: access, training received, confidence and
      use of IT. The survey was carried out in a Sussex Primary Care Trust, in the UK.
      RESULTS: The questionnaire was sent to 109 nurses with a 64% response rate. Most
      primary care nurses (89%) use their computer regularly at work: 100% of practice
      nurses daily, compared with 60% of district nurses and 59% of health visitors (p
      < 0.01). Access to IT was not significantly different between different age
      groups; but 91% of practice nurses had their own computer while many district
      nurses and health visitors had to share (p < 0.01). Nurses over 50 had received
      more training that their younger colleagues (p < 0.01); yet despite this, they
      lacked confidence and used computers less (p < 0.001). 96% of practice nurses
      were confident at in using computerised medical records, compared with 53% of
      district nurses and 44% of health visitors (p < 0.01.) One-to-one training and
      workshops were the preferred formats for training, with Internet based learning
      and printed manuals the least popular (p < 0.001). CONCLUSIONS: Using computers
      in the surgery has become the norm for primary care nurses. However, nurses over
      50, working out in the community, lack the confidence and skill of their younger
      and practice based colleagues.

PMID- 15469615
TI  - The role of hemodialysis machines dedication in reducing Hepatitis C transmission
      in the dialysis setting in Iran: a multicenter prospective interventional study.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is a significant problem among
      patients undergoing maintenance hemodialysis (HD). We conducted a prospective
      multi-center study to evaluate the effect of dialysis machine separation on the
      spread of HCV infection. METHODS: Twelve randomly selected dialysis centers in
      Tehran, Iran were randomly divided into two groups; those using dedicated
      machines (D) for HCV infected individuals and those using non-dedicated HD
      machines (ND). 593 HD cases including 51 HCV positive (RT-PCR) cases and 542 HCV
      negative patients were enrolled in this study. The prevalence of HCV infection in
      the D group was 10.1% (range: 4.6%- 13.2%) and it was 7.1% (range: 4.2%-16.8%) in
      the ND group. During the study conduction 5 new HCV positive cases and 169 new
      HCV negative cases were added. In the D group, PCR positive patients were
      dialyzed on dedicated machines. In the ND group all patients shared the same
      machines. RESULTS: In the first follow-up period, the incidence of HCV infection
      was 1.6% and 4.7% in the D and ND group respectively (p = 0.05). In the second
      follow-up period, the incidence of HCV infection was 1.3% in the D group and 5.7%
      in the ND group (p < 0.05). CONCLUSIONS: In this study the incidence of HCV in HD
      patients decreased by the use of dedicated HD machines for HCV infected patients.
      Additional studies may help to clarify the role of machine dedication in
      conjunction with application of universal precautions in reducing HCV
      transmission.

PMID- 15469617
TI  - The validity of the SF-36 in an Australian National Household Survey:
      demonstrating the applicability of the Household Income and Labour Dynamics in
      Australia (HILDA) Survey to examination of health inequalities.
AB  - BACKGROUND: The SF-36 is one of the most widely used self-completion measures of
      health status. The inclusion of the SF-36 in the first Australian national
      household panel survey, the Household, Income and Labour Dynamics in Australia
      (HILDA) Survey, provides an opportunity to investigate health inequalities. In
      this analysis we establish the psychometric properties and criterion validity of
      the SF-36 HILDA Survey data and examine scale profiles across a range of measures
      of socio-economic circumstance. METHODS: Data from 13,055 respondents who
      completed the first wave of the HILDA Survey were analysed to determine the
      psychometric properties of the SF-36 and the relationship of the SF-36 scales to
      other measures of health, disability, social functioning and demographic
      characteristics. RESULTS: Results of principle components analysis were similar
      to previous Australian and international reports. Survey scales demonstrated
      convergent and divergent validity, and different markers of social status
      demonstrated unique patterns of outcomes across the scales. CONCLUSION: Results
      demonstrated the validity of the SF-36 data collected during the first wave of
      the HILDA Survey and support its use in research examining health inequalities
      and population health characteristics in Australia.

PMID- 15469619
TI  - Vaccination of mice with a 30 kDa Schistosoma antigen with and without human
      adjuvant induces high protection against S. mansoni infection.
AB  - A 30 kDa antigen was characterized as a hydrophobic polypeptide containing 16
      amino acids and evaluated as a potential candidate vaccine against infection by
      Schistosoma mansoni. CD1 albino mice immunized at 0, 14, and 21 days with 25 or
      50 microg of the 30 kDa antigen per mouse with and without alum developed high
      levels of IgG antibodies (predominantly IgG2a and IgG2b isotypes). When immunized
      mice were infected with 200 S. mansoni cercariae, the highest protection levels
      (61% and 65% reduction in worm burden in two separate experiments) were obtained
      using the 50-microg antigen without alum adjuvant. The granuloma size decreased
      to 10%, a non-significant level in mice immunized using alum adjuvant. The
      results demonstrate the ability of the 30 kDa antigen with and without alum
      adjuvant to protect mice against S. mansoni infection.

PMID- 15469618
TI  - Classification between normal and tumor tissues based on the pair-wise gene
      expression ratio.
AB  - BACKGROUND: Precise classification of cancer types is critically important for
      early cancer diagnosis and treatment. Numerous efforts have been made to use gene
      expression profiles to improve precision of tumor classification. However,
      reliable cancer-related signals are generally lacking. METHOD: Using recent
      datasets on colon and prostate cancer, a data transformation procedure from
      single gene expression to pair-wise gene expression ratio is proposed. Making use
      of the internal consistency of each expression profiling dataset this
      transformation improves the signal to noise ratio of the dataset and uncovers new
      relevant cancer-related signals (features). The efficiency in using the
      transformed dataset to perform normal/tumor classification was investigated using
      feature partitioning with informative features (gene annotation) as
      discriminating axes (single gene expression or pair-wise gene expression ratio).
      Classification results were compared to the original datasets for up to 10
      feature model classifiers. RESULTS: 82 and 262 genes that have high correlation
      to tissue phenotype were selected from the colon and prostate datasets
      respectively. Remarkably, data transformation of the highly noisy expression data
      successfully led to lower the coefficient of variation (CV) for the within-class
      samples as well as improved the correlation with tissue phenotypes. The
      transformed dataset exhibited lower CV when compared to that of single gene
      expression. In the colon cancer set, the minimum CV decreased from 45.3% to
      16.5%. In prostate cancer, comparable CV was achieved with and without
      transformation. This improvement in CV, coupled with the improved correlation
      between the pair-wise gene expression ratio and tissue phenotypes, yielded higher
      classification efficiency, especially with the colon dataset - from 87.1% to
      93.5%. Over 90% of the top ten discriminating axes in both datasets showed
      significant improvement after data transformation. The high classification
      efficiency achieved suggested that there exist some cancer-related signals in the
      form of pair-wise gene expression ratio. CONCLUSION: The results from this study
      indicated that: 1) in the case when the pair-wise expression ratio transformation
      achieves lower CV and higher correlation to tissue phenotypes, a better
      classification of tissue type will follow. 2) the comparable classification
      accuracy achieved after data transformation suggested that pair-wise gene
      expression ratio between some pairs of genes can identify reliable markers for
      cancer.

PMID- 15469620
TI  - Equal partnership: two trematode species, not one, manipulate the burrowing
      behaviour of the New Zealand cockle, Austrovenus stutchburyi.
AB  - Metacercariae of the trematode Curtuteria australis (Echinostomatidae) accumulate
      in the foot of the New Zealand cockle Austrovenus stutchburyi, severely impairing
      the cockle's ability to burrow under the sediments. This results in increased
      predation by birds on cockles, and thus enhanced transmission rates of the
      parasite to its bird definitive hosts. This host manipulation by the trematode is
      costly: fish regularly crop the tip of the foot of cockles stranded on the
      sediment surface, killing any metacercariae they ingest. A second, previously
      undetected trematode species (characterized by 23 collar spines) co-existing with
      C. australis, has been found in the foot of cockles in the Otago Harbour, South
      Island, New Zealand. The relative abundance of the two species varies among
      localities, with the identity of the numerically dominant species also changing
      from one locality to the next. Both C. australis and the new species have a
      strong preference for encysting in the tip of the cockle's foot, where their
      impact on the burrowing ability of the host is greatest, and where they both face
      the risk of cropping by fish. Results indicate that these two species are
      ecological equivalents, and their combined numbers determine how the cockle
      population is affected.

PMID- 15469621
TI  - Utilization of brown trout Salmo trutta by Acanthocephalus clavula in an Irish
      lake: is this evidence of a host shift?
AB  - The population biology of the fish acanthocephalan Acanthocephalus clavula was
      described from 161 wild brown trout, Salmo trutta sampled over a two-year period
      in Clogher Lake in the west of Ireland. Overall prevalence of the parasite was
      86% and the mean abundance was 53 worms per fish. Despite the presence of large
      numbers of worms in the trout very few females (2%) attained full reproductive
      maturity. This suggests that trout is an accidental host. A sample of yellow
      eels, Anguilla anguilla was examined at a different time from the same lake. The
      prevalence of A. clavula was 97% and the average abundance was 8 worms per fish.
      In contrast to the situation in trout, the proportion of female worms attaining
      full reproductive maturity was 61% fulfilling the expected characteristic of a
      preferred definitive host. The possible explanations for the very high abundance
      of A. clavula in trout are discussed and include the influence of fluctuations in
      host populations, host diet and the absence of a potential competitor.

PMID- 15469622
TI  - Lack of evidence for co-speciation in a parasitic nematode of grey kangaroos.
AB  - Multilocus enzyme electrophoresis was used to compare specimens of the parasitic
      nematode Cloacina obtusa from the stomach of the eastern grey kangaroo, Macropus
      giganteus and the western grey kangaroo, M. fuliginosus. Allelic variation among
      nematodes was detected at 17 (85%) of 20 loci, but there was only a single fixed
      genetic difference (at the locus for isocitrate dehydrogenase, IDH) between C.
      obtusa from M. fuliginosus and those from M. giganteus in areas where each host
      occurred in allopatry. However, this fixed difference was not apparent within the
      zone of host sympatry. Although electrophoretic data indicate genetic divergence
      among allopatric populations of C. obtusa in the two host species, the magnitude
      of the electrophoretic difference (5%) between these populations does not refute
      the hypothesis that C. obtusa represents a single species. The 'usual' situation
      for parasitic helminths of grey kangaroos is that pairs of parasite species occur
      in the two host species. This situation differs for C. obtusa, where there has
      been a lack of speciation following a speciation event in its macropodid
      marsupial hosts. This finding suggests that a speciation event in the host does
      not necessarily lead to a speciation event for all its parasites and further
      highlights our lack of understanding of which processes drive speciation in
      parasites.

PMID- 15469623
TI  - Larval productivity of Fasciola gigantica in two lymnaeid snails.
AB  - Two groups of Galba truncatula and two groups of Lymnaea natalensis were
      experimentally infected with Fasciola gigantica to determine if snail species had
      an influence on the redial burden and cercarial shedding of this trematode when
      snails of both species were infected with the same isolate of miracidia. In the
      two groups used for the study of redial burden, the total number of free rediae
      was significantly higher at day 49 post-exposure in L. natalensis than in G.
      truncatula. In the groups used for cercarial shedding, the life-span of cercaria
      shedding snails and those of infected snails which died without cercarial
      emission, and the duration of the prepatent period were significantly longer in
      L. natalensis than those noted in G. truncatula. However, the mean numbers of
      shed cercariae did not significantly differ and showed no differences in their
      daily distribution throughout the shedding period. These results demonstrate that
      G. truncatula might be the principal intermediate host of F. gigantica in Egypt,
      at least in the areas where this lymnaeid species lives.

PMID- 15469624
TI  - The helminth community of the wood mouse, Apodemus sylvaticus, in the Sierra
      Espuna, Murcia, Spain.
AB  - The helminth community of the wood mouse, Apodemus sylvaticus, in the Sierra
      Espuna was characterized after a complete analysis of its helminth community
      component and infracommunity structure relative to host age, sex and year of
      capture. The helminth community comprised 13 species: one trematode, four
      cestodes and eight nematodes. The cestode Pseudocatenotaenia matovi and the
      nematode Syphacia frederici were the most prevalent and abundant helminth
      species, respectively. Sixty four percent of mice analysed presented helminths
      with a direct cycle and 42% presented helminths with an indirect cycle. The
      helminth community presents a low diversity with infracommunities usually made up
      of only one or two helminth species. Host age and year of capture seem to play a
      major role in determining species richness and helminth diversity, but not in
      determining the abundance of helminths. Host sex does not seem to affect the
      infection rate nor the diversity. Further studies on more samples of wood mice
      and other small mammal species in this regional park are needed to explore any
      possible interactions between helminth communities in the host populations.

PMID- 15469625
TI  - Seasonal dynamics of Proteocephalus sagittus in the stone loach Barbatula
      barbatula from the Hana River, Czech Republic.
AB  - The seasonal cycle of the cestode Proteocephalus sagittus (Cestoda:
      Proteocephalidae) was studied for the first time in the stone loach Barbatula
      barbatula from the Hana River, Czech Republic. A total of 180 loaches were
      examined monthly from January to December 2001. The parasite occurred in loaches
      throughout the year but infection parameters differed significantly among
      seasons, with the highest values of prevalence and abundance from the late winter
      to the early summer. Parasite recruitment took place in the winter and early
      spring and the worms sexually matured in the late spring and early summer. In
      contrast to P. torulosus, the gravid worms of which laid eggs only at the end of
      the spring/beginning of the summer, gravid worms of P. sagittus were also found,
      although in low numbers, in the autumn and early winter. The rate of infection of
      loach with P. sagittus was neither dependent on the sex nor on the size of its
      fish host.

PMID- 15469626
TI  - Evolutionary relationships within 'pygmaeus' group microphallids using genetic
      analysis and scanning electron microscopy.
AB  - There are four species of 'pygmaeus' microphallids, namely Microphallus pygmaeus,
      M. piriformes, M. pseudopygmaeus and M. triangulatus (Trematoda: Microphallidae)
      which are parasites of marine birds and their sporocysts give rise to
      transmissible metacercariae inside littoral gastropods (mostly littorines).
      Universally primed polymerase chain reaction (UP-PCR) showed no apparent pattern
      between genetic diversity of the metacercariae as estimated by genomic banding
      profiles and their geographic region or molluscan host species. At the same time
      UP-PCR product cross-hybridization showed that M. pseudopygmaeus and M.
      triangulatus are genetically very similar, indicating that these taxa represent
      one species complex. In contrast, M. pygmaeus and M. piriformes are genetically
      well separated from each other and also from the pseudopygmaeus-triangulatus
      complex. Scanning electron microscopy of ventral spines, and analyses of spine
      angles and the number of teeth per spine, showed that all species differed
      significantly from one another. It was concluded that M. piriformes represents
      the original western member of the 'pygmaeus' group. Microphallus pygmaeus
      probably diverged from M. piriformes as it progressively specialized for sea duck
      final hosts. Microphallus pseudopygmaeus and M. triangulatus diverged from each
      other and the piriformes-pygmaeus ancestral line relatively recently.
      Microphallus pseudopygmaeus specialized for adoption of a wide range of gastropod
      host species and M. triangulatus developed morpho-functional specialization
      associated with final host exploitation.

PMID- 15469627
TI  - Epidemiology of alveolar echinococcosis in southern Cantal, Auvergne region,
      France.
AB  - Alveolar echinococcosis (AE) is a helminth zoonosis which is encountered only in
      the northern hemisphere. In central France, the Auvergne region represents the
      most western and southern extension of this helminthiasis. In 1999, a human case
      of AE was diagnosed in the southern part of the Cantal department, where AE was
      supposed absent, and an epidemiological survey was subsequently carried out. The
      transmission of the zoonosis in the sylvatic and peridomestic definitive hosts
      was studied, as well as that in the rodent and human intermediate hosts. Eleven
      red foxes (Vulpes vulpes) were shot, and 50 fox faecal deposits were collected.
      Twelve farm dogs had their faeces taken by rectal touch, and four were checked
      after arecoline purgation. Optical detection of Echinococcus multilocularis worms
      was achieved on fox intestines after scraping, and also on dog stools after
      arecoline therapy. Coproantigen ELISA assay was performed for the 11 scraping
      products, for the 50 fox faeces, and for the 12 dog faecal samples. No adult AE
      agent was observed by microscopy, and the ELISA assay yielded positive results in
      one of 11 fox intestines, one of 50 fox faeces, and 2 of 12 dog faecal samples.
      Twenty-five small mammals were trapped, of which 19 were Arvicola terrestris
      water voles. One rodent liver exhibited a hepatic lesion consistent with AE. An
      epidemiological questionnaire was completed in 85 human volunteers, who were also
      serologically tested for AE. Only one (the case's husband) exhibited a Western
      blotting pattern indicative of a low-grade AE infection. The results of this
      preliminary study suggested a slow AE extension to the south of Cantal department
      from the northern focus.

PMID- 15469628
TI  - Heat shock protein synthesis over time in infective Trichinella spiralis larvae
      raised in suboptimal culture conditions.
AB  - Changes in the viability, infectivity and heat shock protein (Hsp) levels are
      reported in Trichinella spiralis first stage larvae (L1) stored in 199 medium for
      up to seven days at 37 degrees C. These conditions induce stress that the larvae,
      eventually, cannot overcome. After three days of storage, the infectivity and
      viability were unchanged, although higher Hsp70 levels were observed. After this
      time, larvae gradually lost viability and infectivity, coinciding with a decrease
      in Hsp70 and Hsp90 and an increase in actin (a housekeeping protein). In
      addition, a possibly inducible heat shock protein, Hsp90i, appeared as
      constitutive Hsp90 disappeared. No significant changes in Hsp60 levels were
      detected at any time. These results suggest that heat shock proteins initially
      try to maintain homeostasis, but on failing, may be involved in cell death.

PMID- 15469629
TI  - The responses of a tropical breed of domestic rabbit, Oryctolagus cuniculus, to
      experimental infection with Trichostrongylus colubriformis.
AB  - Clinical, parasitological and pathological responses of a tropical out-bred
      domestic rabbit to experimental Trichostrongylus colubriformis infection were
      used to evaluate its suitability as a laboratory host and model for studying the
      host-parasite relationships of T. colubriformis. In the first experiment, three
      groups each of 16, predominantly juvenile male, 8- to 10-week-old rabbits were
      given a single pulse infection with 500, 5000 or 25000 infective larvae (L3) of
      T. colubriformis, to represent low, medium and high levels of infection,
      respectively. A fourth group of 16 rabbits of similar age formed the uninfected
      controls. In the second experiment, two groups of 10 juvenile (8- to 10-week-old)
      and 10 adult (8- to 10-month-old) rabbits were similarly infected with 20000 L3,
      with appropriate naive controls. Prepatency was 14 and 16 days and peak faecal
      egg counts occurred on days 24 and 20 after infection in young and adult rabbits
      respectively. Peak worm counts occurred on day 14 in both age groups and at all
      levels of infection. Subsequently, parasite burdens declined in a highly
      significantly dose- and age-dependent manner. At low and moderate levels of
      infection, approximately 83-98% of worms were recovered from the first 60 cm of
      the small intestine. Worm fecundity was also significantly influenced by host age
      and larval dose. Host age also had a significant effect on worm length.
      Infections with T. colubriformis were associated with a highly significant loss
      of body weight, accompanied by anorexia, diarrhoea and 25% mortality at high dose
      levels during the patent period of infection. There were no significant changes
      in packed cell volume and eosinophil counts at all ages and levels of infection
      but significant lymphocytosis occurred at the high dose level between days 7 and
      21. Parasite-specific serum IgG responses were not related to worm burden.
      Overall, data showed that this miniature, docile and relatively inexpensive breed
      of rabbit is a potentially valuable laboratory host for studying T. colubriformis
      infections. The larval dose, duration of infection and host age were major
      determinants of host responsiveness to primary infections in this rabbit
      genotype.

PMID- 15469630
TI  - Prevalence and pathology of helminths of ciconiiform birds from the Brazilian
      swamplands.
AB  - The prevalence of helminths recovered from 108 birds representing eight species
      of Ciconiiformes from the Brazilian west-central region are presented. The
      digeneans Ascocotyle (Phagicola) longa, Clinostomum marginatum, Cotylotretus
      grandis, Ithyoclinostomum dimorphum, the nematodes Contracaecum multipapillatum,
      Desmidocercella ardeae, Eustrongylides ignotus, and the cestode Valipora
      mutabilis were identified. Contracaecum multipapillatum was the most prevalent
      species and E. ignotus the most pathogenic. Gross lesions due to infections with
      C. multipapillatum were characterized by ulcerative processes and hyperemia of
      the mucosa whereas those caused by E. ignotus consisted of perforations of the
      gastric mucosa and fibrotic tubular lesions in the gastric serosa.
      Histopathological examinations revealed necrosis and mixed leucocyte
      infiltrations and discrete compression of the mucosa in C. multipapillatum
      infections. Destruction of the mucosa and submucosa with the presence of fibrous
      capsules were observed in E. ignotus infections. Reports of accidental human
      infections, with severe clinical signs induced by these parasites, indicate the
      necessity of a proper evaluation of the pathogenicity of helminths of aquatic
      birds.

PMID- 15469631
TI  - Epidemiology of cerebrospinal Elaphostrongylus cervi infection in red deer in
      central Spain.
AB  - Elaphostrongylus cervi produces a subclinical cerebrospinal disease in many wild
      and domestic ruminants from Europe, North America and New Zealand and has
      recently been described in Spain. To determine some aspects of its epidemiology,
      121 red deer (Cervus elaphus) from central Spain were sampled during 2000. The
      prevalence (7%) and mean worm burden (3.8 worms per brain) were similar to the
      values previously recorded in other European areas. The infection was only
      detected in young deer during the winter. The estimation of larval production in
      the faeces was not a reliable method of diagnosing E. cervi infection.

PMID- 15469632
TI  - Intestinal anisakiasis in Italy: case report.
AB  - A case of intestinal anisakiasis caused by Anisakis sp. larva type I in a woman
      from Italy who consumed raw marinated anchovies, is reported. The diagnosis was
      based on the morphological features characteristic of anisakid larval stages,
      which were readily recognized in a large granuloma removed after emergency
      surgical treatment.

PMID- 15469633
TI  - Natural infection of the gerbil Meriones lybicus with the metacestode of Taenia
      endothoracicus in Arak, central Iran.
AB  - Polycephalic larvae of Taenia endothoracicus were found from naturally infected
      gerbils Meriones lybicus in a rural area of Arak, central Iran. A large cyst
      containing 19 protoscolices was located in the peritoneum, attached to the large
      omentum. The characteristics of the protoscolices and rostellar hooks confirmed
      the identification of these larvae as T. endothoracicus.

PMID- 15469634
TI  - Effects of snail size on encystment of Echinostoma caproni in juvenile
      Biomphalaria glabrata (NMRI strain) and observations on the survival of infected
      snails.
AB  - The effects of snail size on encystment of Echinostoma caproni cercariae in
      neonatal and juvenile Biomphalaria glabrata (NMRI strain) snails were studied.
      Encystment in neonatal (0.7-1.1 mm shell diameter) and juvenile (2-3 mm shell
      diameter) snails was compared 24 h post-infection (PI) following individual
      exposure of snails of each size to 1, 5, 10, 25 and 50 cercariae. Significantly
      more cysts were recovered from juveniles exposed to 1, 5, 10 and 50 cercariae
      than from neonatals with comparable exposure. Size of B. glabrata was a major
      factor in determining cyst burden in this planorbid. Survival of infected versus
      uninfected neonatals and juveniles was also examined for 7 days. Neonatals
      exposed to 10 cercariae showed a significant decrease in survival at 3, 6 and 7
      days PI when compared to the uninfected controls. There was no significant
      decrease in the survival of juveniles exposed to 10 cercariae compared to
      uninfected controls at any time point. Snail size was a factor in mortality
      associated with echinostome cercarial penetration and encystment.

PMID- 15469635
TI  - Schistosoma bovis in western Uganda.
AB  - During routine parasitological surveillance and monitoring activities within a
      National Control Programme for control of human schistosomiasis in Uganda, it was
      noted that cattle grazing in a water meadow immediately adjacent to Tonya primary
      school, where the prevalence of intestinal schistosomiasis in children was in
      excess of 90%, were unusually emaciated. To test the hypothesis that there may
      have been an anthropozoonotic focus of Schistosoma mansoni within the local herd,
      a young female heifer, clearly emaciated and c. 8 months old, was slaughtered
      from which schistosome worms were later recovered by dissection. As female worms
      inspected by microscopy were not gravid, morphological identification proved
      inconclusive but analysis of cytochrome oxidase subunit I (COI) and small subunit
      (SSU) ribosomal DNA sequences from these worms identified them as Schistosoma
      bovis Sonsino, 1876. This is the first substantiated report of S. bovis from Lake
      Albert, western Uganda. Further epidemiological surveys are needed to clarify the
      extent of bovine schistosomiasis within this region, particularly so since this
      lakeside plain has been earmarked as a future game reserve.

PMID- 15469636
TI  - Lesions in the liver of guinea-pigs infected with the swine lungworm,
      Metastrongylus apri.
AB  - Clear spot lesions were formed on the liver surface in guinea-pigs repeatedly
      infected with swine lungworm, Metastrongylus apri. The largest lesion, measuring
      0.25 cm in diameter, was hard and yellow and showed a large granuloma in the
      lobule. The nematode larva was located at the centre of the lesion. This finding
      is likely to be an example of erratic parasitism in guinea-pigs with
      metastrongylidiasis.

PMID- 15469637
TI  - Adherence to the Mediterranean dietary pattern among the population of the
      Balearic Islands.
AB  - The aim of the present study was to assess the prevalence of the Mediterranean
      dietary pattern (MDP) in the population of the Balearic Islands and socio
      demographic and lifestyle factors that might determine adherence to the MDP. A
      cross-sectional nutritional survey was carried out in the Balearic Islands
      between 1999 and 2000. A random sample (n 1200) of the adult population (16-65
      years) was interviewed. Dietary questionnaires incorporating questions related to
      socio-economic status, education level, lifestyle factors and health status were
      utilised. Dietary habits were assessed by means of two 24 h recalls, and a
      quantitative food-frequency questionnaire. Adherence to the MDP was defined
      according to a score constructed considering the consumption of nine MDP
      characteristic components: high MUFA:saturated fatty acids ratio, moderate
      ethanol consumption, high legumes, cereals and roots, fruits, vegetables, and
      fish consumption, and low consumption of meat and milk. Then, socio-demographic,
      lifestyle and health status variables that could determine a higher or lower
      adherence were assessed. Adherence to the MDP among the population of the
      Balearic Islands was found to be 43.1 (sd 5.8)%, and was similar in all socio
      demographic and lifestyle groups, with some differences according to age, sex and
      physical status. There was an increase in the percentage of adherence with age,
      which was greater in males than in females. A more physically active lifestyle
      was associated with a higher adherence to the MDP. The promotion of the
      Mediterranean lifestyle, including the MDP and greater physical activity, should
      be reinforced in the population of the Balearic Islands and especially in the
      younger generations.

PMID- 15469638
TI  - Adipokines: inflammation and the pleiotropic role of white adipose tissue.
AB  - White adipose tissue is now recognised to be a multifunctional organ; in addition
      to the central role of lipid storage, it has a major endocrine function secreting
      several hormones, notably leptin and adiponectin, and a diverse range of other
      protein factors. These various protein signals have been given the collective
      name 'adipocytokines' or 'adipokines'. However, since most are neither
      'cytokines' nor 'cytokine-like', it is recommended that the term 'adipokine' be
      universally adopted to describe a protein that is secreted from (and synthesised
      by) adipocytes. It is suggested that the term is restricted to proteins secreted
      from adipocytes, excluding signals released only by the other cell types (such as
      macrophages) in adipose tissue. The adipokinome (which together with lipid
      moieties released, such as fatty acids and prostaglandins, constitute the
      secretome of fat cells) includes proteins involved in lipid metabolism, insulin
      sensitivity, the alternative complement system, vascular haemostasis, blood
      pressure regulation and angiogenesis, as well as the regulation of energy
      balance. In addition, there is a growing list of adipokines involved in
      inflammation (TNFalpha, IL-1beta, IL-6, IL-8, IL-10, transforming growth factor
      beta, nerve growth factor) and the acute-phase response (plasminogen activator
      inhibitor-1, haptoglobin, serum amyloid A). Production of these proteins by
      adipose tissue is increased in obesity, and raised circulating levels of several
      acute-phase proteins and inflammatory cytokines has led to the view that the
      obese are characterised by a state of chronic low-grade inflammation, and that
      this links causally to insulin resistance and the metabolic syndrome. It is,
      however, unclear as to the extent to which adipose tissue contributes
      quantitatively to the elevated circulating levels of these factors in obesity and
      whether there is a generalised or local state of inflammation. The parsimonious
      view is that the increased production of inflammatory cytokines and acute-phase
      proteins by adipose tissue in obesity relates primarily to localised events
      within the expanding fat depots. It is suggested that these events reflect
      hypoxia in parts of the growing adipose tissue mass in advance of angiogenesis,
      and involve the key controller of the cellular response to hypoxia, the
      transcription factor hypoxia inducible factor-1.

PMID- 15469639
TI  - Bioavailability of angiotensin I converting enzyme inhibitory peptides.
AB  - Hypertension or high blood pressure is a significant health problem worldwide.
      Bioactive peptides that inhibit angiotensin I converting enzyme (ACE) in the
      cardiovascular system can contribute to the prevention and treatment of
      hypertension. These ACE inhibitory peptides are derived from many food proteins,
      especially milk proteins. An ACE inhibitory activity in vitro does not always
      imply an antihypertensive effect in vivo. Even if it does, it is very difficult
      to establish a direct relationship between in vitro and in vivo activity. This is
      mainly due to the bioavailability of the ACE inhibitory peptides after oral
      administration and the fact that peptides may influence blood pressure by
      mechanisms other than ACE inhibition. To exert an antihypertensive effect after
      oral ingestion, ACE inhibitory peptides have to reach the cardiovascular system
      in an active form. Therefore, they need to remain active during digestion by
      human proteases and be transported through the intestinal wall into the blood.
      The bioavailability of some ACE inhibitory peptides has been studied. It is also
      known that (hydroxy)proline-containing peptides are generally resistant to
      degradation by digestive enzymes. Peptides can be absorbed intact through the
      intestine by paracellular and transcellular routes, but the potency of the
      bioactivity after absorption is inversely correlated to chain length. In
      addition, some strategies are proposed to increase the bioavailability of ACE
      inhibitory peptides. Further research into the bioavailability of ACE inhibitory
      peptides will lead to the development of more effective ACE inhibitory peptides
      and foods.

PMID- 15469640
TI  - Meta-analysis of the health effects of using the glycaemic index in meal
      planning.
AB  - Diabetes mellitus and CVD are some of the leading causes of mortality and
      morbidity. Accumulating data indicate that a diet characterised by low-glycaemic
      index (GI) foods may improve the management of diabetes or lipid profiles. The
      objective of the present meta-analysis was to critically analyse the scientific
      evidence that low-GI diets have beneficial effects on carbohydrate and lipid
      metabolism compared with high-GI diets. We searched for randomised controlled
      trials with a crossover or parallel design published in English between 1981 and
      2003, investigating the effect of low-GI v. high-GI diets on markers for
      carbohydrate and lipid metabolism. Unstandardised differences in mean values were
      examined using the random effects model. The main outcomes were fructosamine,
      glycated Hb (HbA1c), HDL-cholesterol, LDL-cholesterol, total cholesterol and
      triacylglycerol. Literature searches identified sixteen studies that met the
      strict inclusion criteria. Low-GI diets significantly reduced fructosamine by 
      0.1 (95 % CI -0.20, 0.00) mmol/l (P=0.05), HbA1c by 0.27 (95 % CI -0.5, -0.03) %
      (P=0.03), total cholesterol by -0.33 (95 % CI -0.47, -0.18) mmol/l (P<0.0001) and
      tended to reduce LDL-cholesterol in type 2 diabetic subjects by -0.15 (95 % CI 
      0.31, -0.00) mmol/l (P=0.06) compared with high-GI diets. No changes were
      observed in HDL-cholesterol and triacylglycerol concentrations. No substantial
      heterogeneity was detected, suggesting that the effects of low-GI diets in these
      studies were uniform. Results of the present meta-analysis support the use of the
      GI as a scientifically based tool to enable selection of carbohydrate-containing
      foods to reduce total cholesterol and to improve overall metabolic control of
      diabetes.

PMID- 15469641
TI  - The trans-10,cis-12 isomer of conjugated linoleic acid reduces hepatic
      triacylglycerol content without affecting lipogenic enzymes in hamsters.
AB  - Conjugated linoleic acid (CLA) refers to the positional and geometric dienoic
      isomers of linoleic acid. The dietary intake of CLA has been associated with
      changes in lipid metabolism. The aim of the present work was to assess the
      effects of the two main isomers of CLA on sterol regulatory element binding
      protein (SREBP)-1a and SREBP-1c mRNA levels, as well as on mRNA levels and the
      activities of several lipogenic enzymes in liver. For this purpose hamsters were
      fed an atherogenic diet supplemented with 5 g linoleic acid, cis-9,trans-11 or
      trans-10,cis-12 CLA/kg diet for 6 weeks. The trans-10,cis-12 isomer intake
      produced significantly greater liver weight, but also significantly decreased
      liver fat accumulation. No changes in mRNA levels of SREBP-1a, SREBP-1c and
      lipogenic enzymes, or in the activities of these enzymes, were observed. There
      was no effect of feeding cis-9,trans-11 CLA. These results suggest that increased
      fat accumulation in liver does not occur on the basis of liver enlargement
      produced by feeding the trans-10,cis-12 isomer of CLA in hamsters. The reduction
      in hepatic triacylglycerol content induced by this isomer was not attributable to
      changes in lipogenesis.

PMID- 15469642
TI  - The effect of six different C18 fatty acids on body fat and energy metabolism in
      mice.
AB  - We studied the effects of five high-fat semi-purified diets varying at a 4% (w/w)
      level in either stearic, oleic, linoleic, alpha-linolenic, or gamma-linolenic
      acid on body fat and energy metabolism in BALB/c mice. A diet containing
      caprylic, capric, lauric, and myristic acid was used as a reference diet and a
      diet with 4% conjugated linoleic acid (CLA) was used as a positive control as it
      is known to effectively lower body fat in mice. The diets were fed for 35 d. Body
      fat was significantly lower in the CLA group than in the other groups but was not
      significantly different among the non-CLA groups. Among the non-CLA groups, the
      linoleic acid group tended to have the highest and the alpha-linolenic acid group
      the lowest proportion of body fat. In energy-balance studies, the percentage of
      energy intake that was stored in the body was significantly lower in the CLA
      group compared with the other dietary groups. The percentage of energy intake
      eliminated in excreta was highest in the stearic acid group followed by the gamma
      linolenic acid group. These results were reflected in apparent fat digestibility,
      which was lowest in the stearic acid group. The percentage of energy intake
      expended as heat was highest in the CLA-fed mice. The results of the present
      study suggest that body fat and energy accretion in mice fed diets containing
      different C18 fatty acids is by far the lowest with CLA and that linoleic acid
      produced the highest fat intake and energy accretion.

PMID- 15469644
TI  - Effect of a gamma-aminobutyric acid-enriched dairy product on the blood pressure
      of spontaneously hypertensive and normotensive Wistar-Kyoto rats.
AB  - We investigated the blood-pressure-lowering effects of gamma-aminobutyric acid
      (GABA) and a GABA-enriched fermented milk product (FMG) by low-dose oral
      administration to spontaneously hypertensive (SHR/Izm) and normotensive Wistar
      Kyoto (WKY/Izm) rats. FMG was a non-fat fermented milk product produced by lactic
      acid bacteria, and the GABA contained in FMG was made from the protein of the
      milk during fermentation. A single oral dose of GABA or FMG (5 ml/kg; 0.5 mg
      GABA/kg) significantly (P<0.05) decreased the blood pressure of SHR/Izm from 4 to
      8 h after administration, but did not increase that of WKY/Izm rats. The
      hypotensive activity of GABA was dose-dependent from 0.05 to 5.00 mg/kg in
      SHR/Izm. During the chronic administration of experimental diets to SHR/Izm, a
      significantly slower increase in blood pressure with respect to the control group
      was observed at 1 or 2 weeks after the start of feeding with the GABA or FMG diet
      respectively (P<0.05) and this difference was maintained throughout the period of
      feeding. The time profile of blood-pressure change due to administration of FMG
      was similar to that of GABA. FMG did not inhibit angiotensin 1-converting enzyme.
      Furthermore, an FMG peptide-containing fraction from reverse-phase chromatography
      lacked a hypotensive effect in SHR/Izm rats. The present results suggest that low
      dose oral GABA has a hypotensive effect in SHR/Izm and that the hypotensive
      effect of FMG is due to GABA.

PMID- 15469643
TI  - Effect of plasma insulin and branched-chain amino acids on skeletal muscle
      protein synthesis in fasted lambs.
AB  - The increase in fractional rate of protein synthesis (Ks) in the skeletal muscle
      of growing rats during the transition from fasted to fed state has been explained
      by the synergistic action of a rise in plasma insulin and branched-chain amino
      acids (BCAA). Since growing lambs also exhibit an increase in Ks with level of
      feed intake, the objective of the present study was to determine if this
      synergistic relationship between insulin and BCAA also occurs in ruminant
      animals. Six 30 kg fasted (72 h) lambs (8 months of age) received each of four
      treatments, which were based on continuous infusion into the jugular vein for 6 h
      of: (1) saline (155 mmol NaCl/l); (2) a mixture of BCAA (0.778 micromol leucine,
      0.640 micromol isoleucine and 0.693 micromol valine/min.kg); (3) 18.7 micromol
      glucose/min.kg (to induce endogenous insulin secretion); (4) co-infusion of BCAA
      and glucose. Within each period all animals received the same isotope of
      phenylalanine (Phe) as follows: (1) L-[1-13C]Phe; (2) L-phenyl-[ring 2H5]
      alanine; (3) L-[15N]Phe; (4) L-[ring 2,6-3H]Phe. Blood was sampled serially
      during infusions to measure plasma concentrations of insulin, glucose and amino
      acids, and plasma free Phe isotopic activity; biopsies were taken 6 h after the
      beginning of infusions to determine Ks in m. longissimus dorsi and vastus muscle.
      Compared with control (saline-infused) lambs, Ks was increased by an average of
      40% at the end of glucose infusion, but this effect was not statistically
      significant in either of the muscles sampled. BCAA infusion, alone or in
      combination with glucose, also had no significant effect on Ks compared with
      control sheep. Ks was approximately 60% greater for vastus muscle than for m.
      longissimus dorsi (P<0.01), regardless of treatment. It is concluded that there
      are signals other than insulin and BCAA that are responsible for the feed-induced
      increase in Ks in muscle of growing ruminant animals.

PMID- 15469645
TI  - Addition of pearl barley to a rice-based diet for newly weaned piglets increases
      the viscosity of the intestinal contents, reduces starch digestibility and
      exacerbates post-weaning colibacillosis.
AB  - The purposes of the present study were to investigate the effects of feeding a
      cereal grain containing NSP on body growth and the intestinal microenvironment of
      recently weaned pigs, and to examine resultant associations with pathogenic
      Escherichia coli in the intestinal tract. In Expt 1, pearl barley, a grain rich
      in soluble NSP, was incorporated (250, 500 or 750 g/kg diet) into a low-fibre
      control diet based on cooked white rice and fed for 7-10 d following weaning.
      Consumption of pearl barley did not significantly alter piglet live-weight gain
      compared with the control cooked rice diet, but it accelerated large intestinal
      growth and fermentation, decreased ileal starch digestibility and increased
      intestinal viscosity. Expt 2 was conducted to determine whether these differences
      would favour proliferation of enterotoxigenic E. coli, the bacterium causing post
      weaning colibacillosis (PWC). Three groups of pigs were weaned onto diets based
      on cooked white rice, rice with 500 g pearl barley/kg, or rice with 500 g pearl
      barley/kg supplemented with exogenous enzymes (Porzyme 8100; Danisco,
      Marlborough, Wilts., UK). Pigs were inoculated orally with haemolytic E. coli
      serovar O8;K87;K88 after weaning. Animals eating the pearl barley had increased
      viscosity of the intestinal contents, greater intestinal colonisation with the E.
      coli strain and more diarrhoea than pigs fed the rice-only diet. The enzymes did
      not reduce viscosity or protect from PWC. The results suggest that pearl barley
      alters the intestinal microenvironment and predisposes to PWC, whilst a low
      viscosity, highly digestible diet based on cooked white rice is protective.

PMID- 15469646
TI  - Influence of Camembert consumption on the composition and metabolism of
      intestinal microbiota: a study in human microbiota-associated rats.
AB  - The objective of the present study was to evaluate the consequence of Camembert
      consumption on the composition and metabolism of human intestinal microbiota.
      Camembert cheese was compared with milk fermented by yoghurt starters and
      Lactobacillus casei as a probiotic reference. The experimental model was the
      human microbiota-associated (HM) rat. HM rats were fed a basal diet (HMB group),
      a diet containing Camembert made from pasteurised milk (HMCp group) or a diet
      containing fermented milk (HMfm group). The level of micro-organisms from dairy
      products was measured in faeces using cultures on a specific medium and PCR
      temporal temperature gradient gel electrophoresis. The metabolic characteristics
      of the caecal microbiota were also studied: SCFA, NH3, glycosidase and reductase
      activities, and bile acid degradations. The results showed that micro-organisms
      from cheese comprised 10(5)-10(8) bacteria/g faecal sample in the HMCp group.
      Lactobacillus species from fermented milk were detected in HMfm rats. Consumption
      of cheese and fermented milk led to similar changes in bacterial metabolism: a
      decrease in azoreductase activity and NH3 concentration and an increase in
      mucolytic activities. However, specific changes were observed: in HMCp rats, the
      proportion of ursodeoxycholic resulting from chenodeoxycholic epimerisation was
      higher; in HMfm rats, alpha and beta-galactosidases were higher than in other
      groups and both azoreductases and nitrate reductases were lower. The results show
      that, as for fermented milk, Camembert consumption did not greatly modify the
      microbiota profile or its major metabolic activities. Ingested micro-organisms
      were able to survive in part during intestinal transit. These dairy products
      exert a potentially beneficial influence on intestinal metabolism.

PMID- 15469647
TI  - The in vivo use of the stable isotope-labelled biomarkers lactose-[15N]ureide and
      [2H4]tyrosine to assess the effects of pro- and prebiotics on the intestinal
      flora of healthy human volunteers.
AB  - Amongst the various claimed beneficial effects of pro- and prebiotics for the
      human host, it has been hypothesised that functional foods are able to suppress
      the generation and accumulation of toxic fermentation metabolites (NH3, p
      cresol). Direct evidence supporting this hypothesis is lacking mainly because of
      the unavailability of reliable biomarkers. Preliminary data indicate that lactose
      [15N]ureide and [2H4]tyrosine may be potential biomarker candidates. The aim of
      the present study was to evaluate the effect of pro- and prebiotics on the
      colonic fate of these biomarkers in a randomised, placebo-controlled, cross-over
      study with nineteen healthy volunteers. At the start of the study and at the end
      of each 2-week study period, during which they were administered either a
      probiotic (n 10; 6.5 x 10(9) Lactobacillus casei Shirota cells twice daily) or a
      prebiotic (n 9; lactulose 10 g twice daily), the volunteers consumed a test meal
      containing the two biomarkers. Urine was collected during 48 h. Results were
      expressed as percentage of the administered dose. As compared with the placebo,
      the decrease in the percentage dose of p-[2H4]cresol in the 24-48 h urine
      fraction was significantly higher after probiotic intake (P=0.042). Similar
      changes were observed for the 15N tracer (P=0.016). After prebiotic intake, a
      significantly higher decrease in the percentage dose of p-[2H4]cresol (P=0.005)
      and 15N tracer (P=0.029) was found in the 0-24 h urine collection. The present
      results demonstrate that suppression of the generation and accumulation of
      potentially toxic fermentation metabolites by pro- and prebiotics can reliably be
      monitored in vivo by the use of stable isotope-labelled biomarkers.

PMID- 15469648
TI  - Different effects of whole milk and a fermented milk with the same fat and
      lactose content on gastric emptying and postprandial lipaemia, but not on
      glycaemic response and appetite.
AB  - Longitudinal studies indicate that milk and fermented milk products lower basal
      plasma cholesterol concentrations, despite their high content of saturated fat,
      and therefore have favourable health effects. However, there have been few
      studies on the postprandial effects of milk products. The present study compared
      the effect of whole milk with a fermented milk, A-38, on postprandial
      carbohydrate and lipid metabolism, gastric emptying and appetite. Eight healthy
      young men participated. On the two test days, they arrived fasting for collection
      of baseline values before consuming the meals, which for a 75 kg subject
      consisted of 1.4 litre milk or fermented milk, plus 165 mg [13C]acetate (for
      later determination of gastric emptying by a [13C]acetate breath test). Lactose
      (15 g) was added to the A-38 meal to equalize the lactose content. Postprandially
      the A-38 meal resulted in a slower gastric emptying rate than milk (P<0.001).
      Furthermore, the A-38 meal resulted in a greater increase and a quicker decrease
      of the triacylglycerol content in all lipoprotein fractions (LDL-fraction,
      P<0.05; other fractions, P<0.001) and of the gastrointestinal hormones
      (cholecystokinin and peptide YY, P<0.05; gastric inhibitory polypeptide and
      glucagon-like polypeptide-1, P<0.001). There were no significant differences in
      appetite sensations (measured by visual analogue scale) or in the glucose and
      insulin response (P>0.10). The slower emptying rate of the liquid phase after the
      A-38 meal is probably due to the higher viscosity of A-38. The lower and more
      prolonged triacylglycerol response after the milk meal might be caused by
      coagulation of milk in the stomach.

PMID- 15469649
TI  - Antioxidant vitamin status in high exposure to oxidative stress in competitive
      athletes.
AB  - We conducted a cross-sectional study in 118 well-trained athletes to investigate
      'high exposure' to sub-deficient antioxidant status, and consequently to
      oxidative damage, in relation to estimated daily energy expenditure (EE) and
      dietary antioxidant intake. Subjects completed 7 d food and activity records.
      Blood samples were obtained on day 8. Of the athletes 81, 60 and 43% had intakes
      of vitamins E, C and beta-carotene below two-thirds of the French RDA
      respectively, which is adjusted for EE (FRDAa). The deficit in vitamin E intake
      was positively correlated with EE (r 0.51, P<0.0001). All the athletes had normal
      plasma vitamins E and C and 14% had marginal plasma beta-carotene. Plasma
      thiobarbituric acid-reactive substances (TBARS) did not increase with increased
      EE. As evidenced by ANOVA, EE-induced vitamin C intakes increased and
      consequently led to increased plasma ascorbic acid concentrations. In male
      athletes, plasma total carotenoids were negatively correlated with plasma TBARS
      concentrations (r -0.31, P<0.006). The relationship between vitamin C intakes and
      plasma concentrations was logarithmic (r 0.59, P< 0.0001). To summarize, it is
      not clear whether vitamin E requirements are overestimated with reference to EE
      in the FRDAa. Daily requirements for vitamin C do not exceed 200 mg. Our present
      results could be interpreted as meaning that carotenoids play a protective role
      as exogenous antioxidants. Carotenoid intakes in athletes must be considered
      carefully.

PMID- 15469650
TI  - Effects of one single bout of low-intensity exercise on postprandial lipaemia in
      type 2 diabetic men.
AB  - Fighting type 2 diabetes and its high risk of CVD, lifestyle intervention with
      diet and exercise is of uttermost importance. Epidemiological studies strongly
      suggest an inverse association between increased physical activity, moderate
      alcohol drinking and the incidence of both type 2 diabetes and CVD. However,
      alcohol is known to increase postprandial lipaemia, a risk marker of CVD, and
      exercise to reduce postprandial lipaemia in healthy individuals. The aim of the
      present study was to investigate how type 2 diabetic men respond, in the
      postprandial period, to a single exercise session feasible to perform on a daily
      basis for type 2 diabetic men. The twelve participants ingested a test meal
      containing 100 g butter, 50 g carbohydrate, together with 40 g alcohol, at each
      meal test, imitating a social meal situation. Two protocols included exercise
      sessions with 40 min at 40% VO2max, one where they exercised 3.5 h after, and
      another the afternoon before the test meal. One protocol was without any
      exercise. No significant effect of low-intensity exercise on postprandial
      lipaemia following a fat-rich meal with alcohol was seen in the middle-aged type
      2 diabetic men.

PMID- 15469651
TI  - Circulating triacylglycerol and apoE levels in response to EPA and
      docosahexaenoic acid supplementation in adult human subjects.
AB  - High doses of n-3 PUFA found in fish oils can reduce the circulating
      concentration of triacylglycerol (TG), which may contribute to the positive
      impact of these fatty acids on the risk of CVD. The present study aimed to
      establish the differential impact of EPA and docosahexaenoic (DHA) on plasma
      lipids and apo in adults. Forty-two normolipidaemic adult subjects completed a
      double-blind placebo controlled parallel study, receiving an EPA-rich oil (4.8 g
      EPA/d), DHA-rich oil (4.9 g DHA/d) or olive oil as control, for a period of 4
      weeks. No effects of treatment on total cholesterol, LDL-cholesterol or HDL
      cholesterol were evident. There was a significant 22 % reduction in TG level
      relative to the control value following the DHA treatment (P=0.032), with the 15
      % decrease in the EPA group failing to reach significance (P=0.258). There were
      no significant inter-group differences in response to treatment for plasma apoA1,
      -C3 or -E levels, although a significant 15 % within-group increase in apoE was
      evident in the EPA (P=0.006) and DHA (P=0.003) groups. In addition, a within
      group decrease in the apoA1:HDL-cholesterol ratio was observed in the DHA group,
      suggesting a positive impact of DHA on HDL particle size. The DHA intervention
      resulted in a significant increase in the proportion of EPA P=0.000 and DHA
      P=0.000 in plasma phospholipids, whilst significant increases in EPA P=0.000 and
      docosapentaenoic acid P=0.002, but not DHA P=0.193, were evident following EPA
      supplementation (P<0.05). Our present results indicate that DHA may be more
      efficacious than EPA in improving the plasma lipid profile.

PMID- 15469652
TI  - The validation of using serum iron increase to measure iron absorption in human
      subjects.
AB  - The objectives of the present study were to study the correlation between the
      change in serum Fe and Fe absorption when administering 100 mg Fe (as FeSO4)
      orally, and to study the correlation between the absorption from a 3 mg and a 100
      mg Fe (as FeSO4) dose. The study was conducted in a group of eleven male blood
      donors, without any evident infection, who had given blood 8 weeks before the
      study. On three consecutive mornings the subjects were served a wheat roll
      fortified with Fe. On the first 2 d the roll was fortified with 3 mg Fe labelled
      with 59Fe; on day 3 the roll was fortified with 100 mg Fe labelled with 55Fe. The
      serum Fe response to the 100 mg dose was followed for 6 h. Fe absorption was
      measured by whole-body counting. High correlations were seen between the
      absorption of Fe and the change in serum Fe after 100 mg Fe (r2 0.94, P<0.001),
      between the absorption from 3 mg and 100 mg Fe (r2 0.88, P<0.001), and between
      the absorption from 3 mg Fe and change in serum Fe after 100 mg Fe (r2 0.90,
      P<0.001). This strengthens the evidence that it is possible to use the change in
      serum Fe as a measure of Fe absorption, e.g. when establishing the relative
      bioavailability for Fe powders. The results also imply that the induced serum Fe
      increase following 100 mg Fe added to a food could predict the Fe absorption of a
      small dose of Fe added to the same meal.

PMID- 15469653
TI  - Plasma folate as marker of folate status in epidemiological studies: the European
      Investigation into Cancer and Nutrition (EPIC)-Potsdam study.
AB  - Folate deficiency is often discussed as a potential risk factor for CVD and some
      cancers. Reliable assessment of folate status in large-scale epidemiological
      studies is therefore of major importance. The present study assessed the value of
      plasma folate (PF) compared with erythrocyte folate (EF) as a marker of folate
      status in 363 participants in the European Investigation into Cancer and
      Nutrition (EPIC)-Potsdam cohort. EF and PF, total homocysteine (tHcy),
      pyridoxine, cobalamin, creatinine, total protein and packed cell volume were
      determined; glutamate carboxypeptidase (GCP) C1561T, reduced folate carrier (RFC)
      G80A and methylenetetrahydrofolate (MTHFR) C677T polymorphisms were analysed.
      Anthropometric measurements were taken and dietary intake was assessed with the
      EPIC-Potsdam food-frequency questionnaire. Comparison of EF and PF with factors
      that may modulate their concentrations was performed. Cross-classification of
      blood folates in quintile categories resulted in correct classification into the
      same or adjacent category of 75.5 % of all subjects. Age, BMI, pyridoxine and
      cobalamin, fruit and vegetable intake, and vitamin supplementation 24 h before
      blood draw were positively associated with EF and with PF. For tHcy an inverse
      association was found. Participants with the MTHFR 677TT genotype showed
      significantly elevated EF concentrations compared with those with 677CT genotype;
      EF and PF were more strongly correlated (r 0.78, P<0.0001) for participants with
      MTHFR 677TT genotype than for those with the 677CC or 677CT genotype. In summary,
      our present results indicate that plasma folate seems to be a suitable marker for
      assessment of folate status for use in large-scale epidemiological studies.

PMID- 15469654
TI  - Socio-economic and behavioural factors are predictors of food use in the National
      Food Stamp Program Survey.
AB  - The unhealthy dietary patterns in the USA especially among low-income households
      demand complex strategies for health promotion. The present paper analysed the
      proximate determinants of 7 d food use by 919 participants in the National Food
      Stamp Program Survey conducted in 1996. The households' consumption of dietary
      energy, carbohydrate, protein, fibre, saturated, monounsaturated and
      polyunsaturated fats, Ca, Fe, beta-carotene and vitamin C were explained by
      background, socio-economic and behavioural factors. Certain methodological issues
      arising in modelling food use data were addressed. The results showed that the
      subjects' knowledge of the US Department of Agriculture food pyramid, reading
      nutrition labels, adopting a low-fat diet, selecting fruits and vegetables,
      saving money at grocery stores and frequency of shopping trips were often
      significantly associated (P<0.05) with the densities of nutrient use. The results
      identified certain aspects of nutrition education programmes that deserve greater
      emphasis for improving diet quality. The model for energy intake indicated that
      disbursing half the food stamp benefits on a 2-week basis and better shopping
      practices can enhance food availability.

PMID- 15469655
TI  - Soyabean protein hydrolysate prevents the development of hypertension in
      spontaneously hypertensive rats.
AB  - The aim of the present study was to investigate the anti-hypertensive and
      angiotensin-converting enzyme (ACE) inhibition effects of soyabean protein
      hydrolysate in spontaneously hypertensive rats (SHR). Soyabean protein
      hydrolysate was prepared by peptic hydrolysis and was added into the feed of SHR
      (0% for the S0 group, 0.5% for the S1 group, and 1% for the S2 group) for 12
      weeks. Systolic blood pressure and mean blood pressure of the S1 (164.3 (sem
      4.7); 128.0 (sem 5.0) mmHg) and S2 (156.8 (sem 1.6); 120.8 (sem 3.4) mmHg) groups
      were significantly lower than those of the S0 group (199.4 (sem 5.2); 158.3 (sem
      7.0) mmHg) at the end of the study. In the analysis of ACE activity, plasma and
      heart ACE activities of the S1 and S2 groups were significantly lower than those
      of the S0 group, and there were no significant differences in aorta, kidney, and
      lung ACE activities among all SHR. Soyabean protein hydrolysate had no
      significant effect on plasma lipids, electrolytes, or on left ventricular wall or
      aorta wall thickness. The results suggest that the long-term administration of
      soyabean protein hydrolysate might retard the development of hypertension in SHR
      by its inhibitory effect on ACE in vivo.

PMID- 15469656
TI  - Prenatal exposure to a maternal low-protein diet programmes a preference for high
      fat foods in the young adult rat.
AB  - Nutrient restriction in pregnancy has been shown to programme adult obesity.
      Modulation of feeding behaviour may provide a mechanism through which obesity may
      be programmed. Pregnant Wistar rats were fed either a control diet or a low
      protein (LP) diet throughout gestation. Their offspring were allocated to a self
      selected-diet protocol to assess appetite and food preferences at 12 and at 30
      weeks of age. Self-selection of high-fat, high-protein or high-carbohydrate foods
      by 12-week-old rats indicated that the prenatal environment influenced feeding
      behaviour. Both male and female offspring of LP-fed mothers consumed
      significantly more of the high-fat (P<0.001) and significantly less (P<0.02) of
      the high-carbohydrate food than the control animals. Female, but not male,
      offspring of LP-fed rats failed to adjust food intake to maintain a constant
      energy intake and had higher fat (P<0.005) and energy intakes (P<0.05) than
      control female rats. At 30 weeks of age there were no differences in the pattern
      of food selection between the two groups of animals. Male offspring of LP-fed
      rats had significantly more gonadal fat than control animals (P<0.05), but
      analysis of total body fat content indicated that there was no significant
      difference in overall adiposity. The present study suggests that in young adults
      at least, early life exposure to undernutrition determines a preference for fatty
      foods. Maternal nutrition may thus promote changes in systems that are involved
      in control of appetite or the perception of palatability.

PMID- 15469657
TI  - Inulin-type fructans modulate gastrointestinal peptides involved in appetite
      regulation (glucagon-like peptide-1 and ghrelin) in rats.
AB  - The hypothesis tested in the present study is that dietary fructans are able to
      modulate gastrointestinal peptides involved in the control of food intake, namely
      glucagon-like peptide (GLP)-1 (7-36) amide and ghrelin. After 3 weeks of
      treatment with a standard diet (control) or the same diet enriched with 100 g
      fructans varying in their degrees of polymerization (oligofructose (OFS), Synergy
      1 (Syn) or long chain inulin)/kg, male Wistar rats were deprived of food for 8 h
      before sample collection. Dietary energy intake throughout the experiment was
      significantly lower (P<0.05) in fructans-fed rats than in control rats, leading
      to a significant decrease (P<0.01) in epidydimal fat mass at the end of the
      treatment in OFS- and Syn-treated rats. GLP-1 (7-36) amide concentration in
      portal vein serum was higher in OFS- and Syn-fed than in control rats. Both GLP-1
      (7-36) amide concentration and proglucagon mRNA concentrations were significantly
      greater (P<0.05) in the proximal colonic mucosa of fructans-fed rats v. controls.
      Normally active ghrelin concentration in plasma increases during food deprivation
      and rapidly falls during a meal. In the present study, after 8 h of food
      deprivation, active ghrelin in the plasma remained significantly lower (P<0.05)
      in OFS and Syn-fed than in control rats. These results are in accordance with the
      modifications of dietary intake and fat-mass development in short-chain fructans
      treated rats and demonstrate the potential modulation of GLP-1 (7-36) amide and
      ghrelin by fermentable fibres such as fructans, which are rapidly and extensively
      fermented in the proximal part of the colon.

PMID- 15469658
TI  - What influences the timing of the introduction of solid food to infants?
AB  - The aim of the present study was to assess the factors which may influence the
      timing of the introduction of solid food to infants. The design was a prospective
      cohort study by interview and postal questionnaire. Primiparous women (n 541)
      aged between 16 and 40 years were approached in the Forth Park Maternity
      Hospital, Fife, Scotland. Of these, 526 women agreed to participate and seventy
      eight were used as subjects in the pilot study. At 12 weeks we interviewed 338
      women of the study sample. The postal questionnaire was returned by 286 of 448
      volunteers. At 12 weeks 133 of 338 mothers said that they had introduced solids.
      Those that said that they had introduced solids early (<12 weeks) were compared
      with those who had introduced solids late (>12 weeks) by bivariate and multiple
      regression analysis. Psychosocial factors influencing the decision were measured
      with the main outcome measure being the time of introduction of solid food. The
      early introduction of solids was found to be associated with: the opinions of the
      infant's maternal grandmother; living in a deprived area; personal disagreement
      with the advice to wait until the baby was 4 months; lack of encouragement from
      friends to wait until the baby was 4 months; being in receipt of free samples of
      manufactured food. Answers to open-ended questions indicated that the early
      introduction appeared to be influenced by the mothers' perceptions of the baby's
      needs. Some of the factors influencing a woman's decision to introduce solids are
      amenable to change, and these could be targeted in educational interventions.

PMID- 15469659
TI  - Long-term almond supplementation without advice on food replacement induces
      favourable nutrient modifications to the habitual diets of free-living
      individuals.
AB  - Epidemiological and metabolic studies have shown that regular nut consumption may
      protect against risk of heart disease and diabetes. None has investigated the
      effect of adding nuts to a self-selected habitual diet (containing little or no
      nuts) on dietary patterns. The present study evaluated the impact of long-term
      almond supplementation in healthy men (n 43) and women (n 38) aged 25-70 years on
      nutrient profile and nutrient displacement. All subjects were followed for 1
      year. During the first 6 months, subjects followed their habitual diets; in the
      second 6 months, subjects added almonds to their diets. Diets were assessed by
      seven random 24 h telephone diet recalls during each diet period. On average, the
      almond supplement was 52 g/d (about forty-two nuts) containing 1286 kJ. When
      subjects changed from their habitual diet to the almond-supplemented diet, the
      intakes of MUFA, PUFA, fibre, vegetable protein, alpha-tocopherol, Cu and Mg
      significantly (P<0.05) increased by 42, 24, 12, 19, 66, 15 and 23% respectively;
      the intakes of trans fatty acids, animal protein, Na, cholesterol and sugars
      significantly (P<0.05) decreased by 14, 9, 21, 17 and 13% respectively. These
      spontaneous nutrient changes closely match the dietary recommendations to prevent
      cardiovascular and other chronic diseases. Displacement estimates for total
      energy, total protein, total fat, SFA, MUFA, PUFA, total fibre, Ca, Fe, Mg, P, K,
      Zn and alpha-tocopherol ranged from 16 to 98%; the estimates for total food
      weight, carbohydrate, sugars and Se were >245%. A daily supplement of almonds can
      induce favourable nutrient modifications for chronic disease prevention to an
      individual's habitual diet.

PMID- 15469660
TI  - Body-weight change during over- and underfeeding as an indicator of adaptive
      thermogenesis.

PMID- 15469664
TI  - Aripiprazole: novelty, adherence and understatement.

PMID- 15469665
TI  - The combination of nicotine with the D2 antagonist raclopride or the weak D4
      antagonist L-745,870 generates a clozapine-like facilitation of NMDA receptor
      mediated neurotransmission in pyramidal cells of the rat medial prefrontal
      cortex.
AB  - Clozapine and other atypical, but not typical, antipsychotic drugs (APDs),
      facilitate both dopaminergic and N-methyl-D-aspartate (NMDA) receptor-mediated
      glutamatergic transmission in the medial prefrontal cortex (mPFC), which is
      thought to improve cognition. Switching schizophrenic patients from typical APDs
      to clozapine may reduce their cigarette smoking. Here, we tested whether
      nicotine, which facilitates dopamine release, also facilitates NMDA receptor
      mediated neurotransmission in the mPFC, when given alone or in combination with a
      D(2,3) antagonist, raclopride, or a D4 antagonist, 3-(4-[4-chlorophenyl]piperazin
      1-yl)methyl-1H-pyrrolo[2,3b]pyridine (L-745,870), using intracellular recording
      in pyramidal cells of the rat mPFC. Neither nicotine nor raclopride or L-745,870
      alone altered NMDA-induced currents in these cells. However, combining nicotine
      with raclopride or L-745,870 facilitated these currents. Similarly to clozapine
      the combination of nicotine with raclopride or L-745,870 also markedly
      potentiated evoked excitatory post-synaptic potentials in the mPFC. Our results
      support the idea that intense smoking in schizophrenia may represent a form of
      self-medication with nicotine.

PMID- 15469666
TI  - Neuroendocrine effects of quetiapine in healthy volunteers.
AB  - The present study measured prolactin, cortisol, ACTH and growth hormone in
      healthy male volunteers following an acute oral administration of quetiapine, an
      atypical antipsychotic with high affinity for H1 and moderate affinity for sigma,
      alpha1, 5-HT2, alpha2 and D2 receptors. Fifteen male volunteers entered this
      randomized double-blind, cross-over, placebo-controlled study. Blood samples were
      drawn every 30 min from 09:00 hours to 13:00 hours. The first samples were drawn
      immediately before the administration of 150 mg quetiapine or placebo. Mean
      results for each hormone and ANOVA for repeated measures were performed. The area
      under the curve (AUC) hormonal values were calculated and compared by paired t
      test. The ANOVA showed an increase of prolactin after quetiapine administration
      from time 60 min up to the end of the observation period. Cortisol decreased
      after quetiapine administration from time 150 min to time 240 min. ACTH secretion
      showed no difference compared to placebo. There was a late increase in growth
      hormone secretion, significant in comparison with placebo only at time 210 min.
      The AUC values were statistically different for prolactin and cortisol compared
      to placebo. A single dose of quetiapine (150 mg) increased prolactin secretion
      probably due to a transiently high D2 receptor occupancy at the anterior
      pituitary. Cortisol secretion decreased as was expected from quetiapine's
      pharmacodynamic profile. The lack of response of ACTH might be, at least in part,
      explained by the low hormonal assay sensitivity. The late growth hormone increase
      might have been due to quetiapine's antagonism of H1 receptors.

PMID- 15469667
TI  - Human 5-HT1A receptor C(-1019)G polymorphism and psychopathology.
AB  - Dysfunction of the serotonin (5-HT1A) receptor (5-HTR1A) has been implicated in
      mood disorders, anxiety disorders, psychosis and the action of antidepressants. A
      common C(-1018)G [C(-1019)G] functional polymorphism in the promoter region of
      the human 5-HT1A receptor gene has been reported, which may be useful in
      identifying psychopathology associated with altered function of the human 5-HT1A
      receptor. We studied the relationship of this polymorphism to psychopathology and
      5-HT1A binding in prefrontal cortex. The 5-HT1A receptor genotype for the C(
      1019)G polymorphism was typed in 696 unrelated psychiatric subjects, 107
      unrelated healthy volunteers, and in post-mortem brain samples from 241 cases. 5
      HT1A receptor binding was assayed in post-mortem prefrontal cortex using [3H]8-OH
      DPAT, and specific binding determined by 1 microM 5-HT. An association of
      genotype distribution and allele frequency of the 5-HTR1A C(-1019)G locus was
      observed in schizophrenia (chi2=9.51, d.f.=2, p=0.009; chi2=9.52, d.f.=1,
      p=0.002; Armitage's trend test: chi2=9.07, d.f.=1, p=0.003), in substance use
      disorder (chi2=8.41, d.f.=2, p=0.015; chi2=8.35, d.f.=1, p=0.004; Armitage's
      trend test: chi2=6.27, d.f.=1, p=0.0012), and in panic attack (chi2=6.31, d.f.=2,
      p=0.043; chi2=6.14, d.f.=1, p=0.013; Armitage's trend test: chi2=6.27, d.f.=1,
      p=0.012). An association of the 5-HTR1A C(-1019)G locus with schizophrenia,
      substance use disorder, and panic attack was suggested by our results. In post
      mortem brain samples, 5-HT1A receptor binding in prefrontal cortex and suicide
      were not associated with genotype. The relationship does not appear to be
      explained by binding differences, although we cannot rule out altered receptor
      affinity and transduction.

PMID- 15469668
TI  - Does comorbid subthreshold anxiety affect clinical presentation and treatment
      response in depression? A preliminary 12-month naturalistic study.
AB  - The aim of this study was to evaluate the effects of comorbid subthreshold
      anxiety on the course and the treatment of Depressive Disorders. The sample
      studied comprised four groups defined by the DSM-IV Axis I diagnosis: (1)
      Patients with a Major Depressive Disorder (MDD) and an Anxiety Disorder (DA); (2)
      patients with MDD and a subthreshold Anxiety Disorder (Da); (3) patients with
      subthreshold depression and an Anxiety Disorder (dA); (4) patients with
      subthreshold depression and subthreshold anxiety (da). HAMD, HAMA and CGI rating
      scales were administered monthly for 12 months while patients were treated with
      different antidepressants. Significant differences were found among the four
      groups with respect to the baseline depressive symptoms: Da presented more
      frequently suicidal ideation (chi2=9.568, d.f.=3, p=0.023), psychomotor
      retardation (chi2=12.568, d.f.=3, p=0.006), sexual dysfunctions (chi2=7.761,
      d.f.=3, p=0.05), hypochondriacal ideation (chi2=13.633, d.f.=3, p=0.003), weight
      loss (chi2=9.520, d.f.=3, p=0.023), and diurnal variation of symptoms
      (chi2=13.258, d.f.=3, p=0.004). With respect to the treatment response Da
      patients showed an overall worse response to antidepressants, having a longer
      latency and a lower reduction of symptoms. These results suggest that patients
      with Major Depression and subthreshold anxiety present with a more severe
      baseline clinical picture and seem to have a less efficient response to
      antidepressants.

PMID- 15469670
TI  - The non-principal phenomenon: a threat to continuity of care and patient
      enablement?

PMID- 15469671
TI  - Occupational asthma case finding: a role for primary care.

PMID- 15469672
TI  - Management in general practice: the challenge of the new General Medical Services
      contract.
AB  - BACKGROUND: Managers in general practice perform a variety of roles, from purely
      administrative to higher-level strategic planning. There has been little research
      investigating in detail how they perform these roles and the problems that they
      encounter. The new General Medical Services (GMS) contract contains new
      management challenges and it is not clear how practices will meet these. AIM: To
      improve understanding of the roles performed by managers in general practice and
      to consider the implications of this for the implementation of the new GMS
      contract. DESIGN OF STUDY: In-depth qualitative case studies covering the period
      before and immediately after the vote in favour of the new GMS contract. SETTING:
      Three general practices in England, chosen using purposeful sampling. METHOD:
      Semi-structured interviews with all clinical and managerial personnel in each
      practice, participant and non-participant observation, and examination of
      documents. RESULTS: Understanding about what constitutes the legitimate role of
      managers in general practice varies both within and between practices. Those
      practices in the study that employed a manager to work at a strategic level with
      input into the direction of the organisation demonstrated significant problems
      with this in practice. These included lack of clarity about what the legitimate
      role of the manager involved, problems relating to the authority of managers in
      the context of a partnership, and lack of time available to them to do higher
      level work. In addition, general practitioners (GPs) were not confident about
      their ability to manage their managers' performance. CONCLUSION: The new GMS
      contract will place significant demands on practice management. These results
      suggest that it cannot be assumed that simply employing a manager with high-level
      skills will enable these demands to be met; there must first be clarity about
      what the manager should be doing, and attention must be directed at questions
      about the legitimacy enjoyed by such a manager, the limits of his or her
      authority, and the management of performance in this role.

PMID- 15469673
TI  - Preferences for general practice jobs: a survey of principals and sessional GPs.
AB  - BACKGROUND: Many countries are experiencing recruitment and retention problems in
      general practice, particularly in rural areas. In the United Kingdom (UK), recent
      contractual changes aim to address general practitioner (GP) recruitment and
      retention difficulties. However, the evidence base for their impact is limited,
      and preference differences between principals and sessional GPs (previously
      called non-principals) are insufficiently explored. AIM: To elicit GP principals'
      and sessional GPs' preferences for alternative jobs in general practice, and to
      identify the most important work attributes. DESIGN OF STUDY: A discrete choice
      experiment. SETTING: National Health Service (NHS) general practices throughout
      Scotland. METHOD: A postal questionnaire was sent to 1862 principals and 712
      sessional GPs. The questionnaire contained a discrete choice experiment to
      quantify GPs' preferences for different job attributes. RESULTS: A response rate
      of 49% (904/1862) was achieved for principals and 54% (388/712) for sessional
      GPs. Of responders, most principals were male (60%), and sessional GPs female
      (75%), with the average age being 42 years. All GPs preferred a job with longer
      consultations, no increase in working hours, but an increase in earnings. A job
      with outside commitments (for example, a health board or hospital) was
      preferable; one with additional out-of-hours work was less preferable. Sessional
      GPs placed a lower value on consultation length, were less worried about hours of
      work, and a job offering sufficient continuing professional development was less
      important. CONCLUSION: The differences in preferences between principals and
      sessional GPs, and also between different personal characteristics, suggests that
      a general contract could fail to cater for all GPs. Recruitment and retention of
      GPs may improve if the least preferred aspects of their jobs are changed.
      However, the long-term success of contractual reform will require enhancement of
      the positive aspects of working, such as patient contact.

PMID- 15469674
TI  - Why do general practitioners from France choose to work in London practices? A
      qualitative study.
AB  - BACKGROUND: Growing concerns about the ability to maintain and increase the
      general practitioner (GP) workforce has led to active recruitment of GPs from
      overseas. However, little is known about why these GPs choose to leave their
      countries and come to work in London. AIM: To investigate the motivations and
      expectations of French GPs migrating to work in general practices in London.
      DESIGN OF STUDY: A qualitative study using semi-structured interviews. SETTING:
      General practice induction programme in southeast London. METHOD: Individual
      interviews with 31 French GPs, who attended an induction programme for
      international recruits, were taped, transcribed, and analysed using a categorical
      approach. RESULTS: Three factors led to the process of migration: instigating
      factors, creating the stimulus for migration; activating factors, based on the
      perception that English general practice offered greater opportunities; and
      facilitating factors, which make migration possible. Particular emphasis was
      placed on personal and professional instigating factors, with a desire for new
      cultural experiences and a widespread discontent surrounding the infrastructure
      of French general practice, playing crucial roles in the stimulus to migrate.
      Ease of travel and a paid induction programme facilitated the move to their
      chosen destination. CONCLUSION: French GPs' decisions were part of a process of
      migration influenced by a series of integrated factors. Consideration of these
      factors will not only enhance recruitment to English general practice, but will
      also facilitate foreign GPs' transition to work in the National Health Service
      (NHS) and, ultimately, maximise their retention.

PMID- 15469675
TI  - Management of acute asthma exacerbations by general practitioners: a cross
      sectional observational survey.
AB  - BACKGROUND: General practitioners (GPs) have a central place in the management of
      asthma, particularly in the context of acute exacerbations. AIM: To evaluate the
      management of asthma exacerbations by GPs, and to investigate the ability of risk
      factors for near fatal asthma to predict the severity of asthma attacks in the
      community. DESIGN OF STUDY: A 1-month multicentre cross-sectional survey.
      SETTING: One thousand and ninety-four GPs of the French Sentinel Network were
      contacted; 365 responded. METHOD: Asthma exacerbations were classified according
      to severity at presentation. Univariate and multivariate analyses were performed
      by logistic regression to identify those factors associated with severe
      exacerbations. RESULTS: Exacerbations were described in 219 patients with asthma.
      Over half (54%) of exacerbations were severe. Peak expiratory flow was recorded
      during the consultation in 55% of patients who were more than 5 years old.
      beta(2) agonists were prescribed to 93% of patients, systemic corticosteroids to
      71%, and antibiotics to 64%. Only 42% of patients had a written action plan for
      self-management of exacerbations. Risk factors for near fatal asthma, identified
      in 26% of patients, were not significantly associated with severe asthma
      exacerbations. Short duration of exacerbation before consultation (<3 hours) was
      associated with an increase in relative risk of severe exacerbation of 3.38, 95%
      confidence intervals (CIs) = 1.19 to 9.61, compared with duration of >3 hours.
      CONCLUSION: Risk factors for near fatal asthma identified in previous studies
      were not predictive of a severe exacerbation in general practice, with the
      exception of short duration of exacerbation before consultation. This suggests
      that new methods to predict risk in the outpatient settings should be developed.

PMID- 15469676
TI  - Cost-effectiveness of implementing new guidelines for treatment of hypertension
      in general practice.
AB  - BACKGROUND: Hypertension is a major public health concern and, as the population
      ages, the size of the problem is likely to increase. However, detection rates and
      treatment of hypertension have been low. The introduction of new guidelines for
      the detection and treatment of hypertension have been encouraged but without any
      consideration to their cost-effectiveness. AIM: To assess the potential cost
      effectiveness of implementing new guidelines for the treatment of hypertension in
      general practice. DESIGN OF STUDY: Model examining the incremental costs and
      effects of the new guidelines compared with the old. SETTING: A large general
      practice in north Yorkshire. METHOD: Two thousand and twenty-three patients
      reporting for a new health patient check had the costs and outcomes under the old
      and new guidelines estimated. RESULTS: Implementing new guidelines for the
      detection, management, and treatment of hypertension in a primary care setting is
      more costly than the implementation of previous guidelines, but more effective in
      reducing the risk of cardiovascular disease. The incremental cost per
      cardiovascular disease event avoided is ?30 000, although sensitivity analysis
      shows that the estimate is subject to considerable uncertainty. CONCLUSIONS:
      Compared with previous guidelines, introducing new guidelines for the management
      and treatment of hypertension in new patients in general practice is likely to be
      cost-effective. However, the workforce implications for general practitioners
      (GPs) and practice nurses should be considered.

PMID- 15469678
TI  - Are general practitioners' assessments of housing applicants' health accurate?
AB  - Public sector housing is often allocated on the basis of the 'vulnerability' of
      applicants. As part of assessing vulnerability, housing departments request
      assessments from applicants' general practitioners (GPs). GP assessments
      submitted over 3 years to a local authority housing department were analysed. The
      nature of the patient group and format of the GP report discriminate against
      accurate reporting and hence fair assignment of housing.

PMID- 15469677
TI  - Valued aspects of primary palliative care: content analysis of bereaved carers'
      descriptions.
AB  - BACKGROUND: Informal carers provide the bulk of palliative home care. They
      largely rely on general practitioners (GPs) and district nurses to support them
      in this role, yet little is known about what carers themselves consider important
      in this support. AIM: To identify what informal carers valued in the palliative
      support provided by GPs and district nurses by using carers' own descriptions of
      such support. DESIGN OF STUDY: Retrospective interviews. SETTING: Primary care in
      Cambridgeshire. METHOD: Semi-structured interviews with bereaved carers of 48
      patients with cancer and 12 patients with non-cancer diagnoses. Content analysis
      of carers' evaluative descriptions of GP and district nurse support. RESULTS: The
      accessibility of the GP and district nurse emerged as the most important aspect
      of support. Enlistment of help from other agencies was also extensively
      mentioned, together with provision of equipment. Attitude or approach during
      interactions, and relationship with the professional were important, particularly
      regarding GP support, whereas support for the carer, information, and symptom
      control were mentioned less often. Data suggested that support was not as good
      for older patients (> or =75 years), but this finding requires further
      investigation. CONCLUSION: Results largely confirmed findings of previous,
      quantitative research and the importance of a patient-centred approach. What
      emerged most strongly, however, was the central importance of accessibility of
      support services for lay carers responsible for end-of-life home care. This
      mainly concerned GP and district nurse support, but accessibility of additional
      care and equipment were also important. In short, carers' main focus was the
      basic support that enabled them to sustain care in the home.

PMID- 15469679
TI  - The outcome of initiation of antiepileptic drug monotherapy in primary care: a UK
      database survey.
AB  - We describe the incidence of newly treated epilepsy in primary care and patterns
      of antiepileptic drug prescription, numbers of patients who remain on initial
      therapy and health service utilisation. Data was collected from 100 general
      practices that subscribed to the Doctors Independent Network (DIN-LINK) project.
      Over the study period 1531 patients were identified, equating to an annual
      incidence rate of 36.3 per 100 000 (95% confidence interval [CI] = 32.1 to 40.8).
      Of these patients, 1465 (95.7%) were started on antiepileptic drugs. Overall,
      1154 (78.8%) patients remained on the original monotherapy at the 12-month stage.
      Primary care consultations, secondary care referrals and emergency admissions
      were all increased for those whose treatment was changed either to polytherapy or
      an alternative monotherapy.

PMID- 15469680
TI  - Fast-track cancer diagnoses.

PMID- 15469681
TI  - Train GPs to provide good sexual health care.

PMID- 15469682
TI  - Jury service is bad for your health.

PMID- 15469683
TI  - Screening for type 2 diabetes.

PMID- 15469684
TI  - Simple and effective treatment for head lice.

PMID- 15469685
TI  - A seemingly ineffective study on menopausal memory problems.

PMID- 15469686
TI  - A year in Afghanistan--Herat hospital paediatric ward.

PMID- 15469687
TI  - An important role of Nrf2-ARE pathway in the cellular defense mechanism.
AB  - The antioxidant responsive element (ARE) is a cis-acting regulatory element of
      genes encoding phase II detoxification enzymes and antioxidant proteins, such as
      NAD(P)H: quinone oxidoreductase 1, glutathione S-transferases, and glutamate
      cysteine ligase. Interestingly, it has been reported that Nrf2 (NF-E2-related
      factor 2) regulates a wide array of ARE-driven genes in various cell types. Nrf2
      is a basic leucine zipper transcription factor, which was originally identified
      as a binding protein of locus control region of beta-globin gene. The DNA binding
      sequence of Nrf2 and ARE sequence are very similar, and many studies demonstrated
      that Nrf2 binds to the ARE sites leading to up-regulation of downstream genes.
      The function of Nrf2 and its downstream target genes suggests that the Nrf2-ARE
      pathway is important in the cellular antioxidant defense system. In support of
      this, many studies showed a critical role of Nrf2 in cellular protection and anti
      carcinogenicity, implying that the Nrf2-ARE pathway may serve as a therapeutic
      target for neurodegenerative diseases and cancers, in which oxidative stress is
      closely implicated.

PMID- 15469688
TI  - Characterization of the nucleotide sequence of a polyubiquitin gene (PUBC1) from
      Arabian camel, Camelus dromedarius.
AB  - Molecular amplification and sequencing of genomic DNA that encodes camel
      polyubiquitin (PUBC1) was performed by a polymerase chain reaction (PCR) using
      various sets of primers. The amplification generated a number of DNA fragments,
      which were sequenced and compared with the polyubiquitin coding sequences of
      various species. One DNA fragment that conformed to 325 bp was found to be 95 and
      88% homologous to the sequences of human polyubiquitin B and C, respectively. The
      DNA translated into 108 amino acids that corresponded to two fused units of
      ubiquitin with no intervening sequence, which indicates that it is a
      polyubiquitin and contains at least two units of ubiquitin. Although, variations
      were found in the nucleotide sequence when compared to those of other species,
      the amino acid sequence was 100% homologous to the polyubiquitin sequences of
      humans, mice, and rats. This is the first report of the polyubiquitin DNA coding
      sequence and its corresponding amino acid sequence from camels, amplified using
      direct genomic DNA preparations.

PMID- 15469689
TI  - An oligonucleotide microarray bait for isolation of target gene fragments.
AB  - A new molecular-baiting method was studied by retrieving targeted gene fragments
      from an oligonucleotide microarray bait after hybridization. To make the
      microarray bait, 70-mer oligonucleotides that were designed to specifically
      represent the SSA1 gene of Saccharomyces cerevisiae were printed on the slide.
      Samples of the Saccharomyces cerevisiae mRNA were extracted and labeled by the RD
      PCR (Restriction Display PCR) method using the Cy5-labelled universal primer,
      then applied for hybridization. The sample fragments that hybridized to the
      microarray were stripped, and the eluted cDNAs were retrieved and cloned into the
      pMD 18-T vector for transformation, plasmid preparation, and sequencing. BLAST
      searching of the GenBank database identified the retrieved fragments as being
      identical to the SSA1 gene (from 2057-2541bp). A new method is being established
      that can retrieve the sample fragments using an oligo-microarray-bait.

PMID- 15469690
TI  - Characterization of insulin-like growth factor-free interaction between insulin
      like growth factor binding protein 3 and acid labile subunit expressed from
      Xenopus oocytes.
AB  - The acid-labile subunit (ALS) is known to interact with the IGF binding protein
      (IGFBP) in the presence of insulin-like growth factors (IGFs). Studies, however,
      indicate that ALS forms a doublet with IGFBP3, independent of IGFs. To
      characterize the structural domain required for the IGF-free ALS-IGFBP3
      interaction, seven recombinant human IGFBP3 mutants were generated: three
      deletion mutants and four site-specific mutants that had altering N-terminal
      regions of IGFBP3. ALS and IGFBP3 mRNAs were co-injected into Xenopus oocytes,
      and their products were cross-linked and immunoprecipitated using antisera
      against ALS or IGFBP3. Among the deletion mutants, the mutant of D40 (deleted in
      11-40th amino acids) exerted no effect in the interaction with ALS, while D60
      (Delta11-60) demonstrated a moderate reduction. D88 (Delta11-88), however, showed
      a significant decrease. In the case of site-specific mutants, the mutation that
      alterated the IGF binding site (codons 56 or 80) exerted a significant reduction
      in the interaction, whereas codons 72 or 87 showed no significant change in the
      interaction with ALS. The stability of the ALS-IGFBP3 interaction was analyzed
      according to a time-dependent mode. Consistent with the binding study, mutants on
      the IGF binding sites (56 or 80) consistently show a weakness in the ALS-IGFBP3
      interaction when compared to the mutants that covered the non-IGF binding sites
      (72 or 87). This study suggests that the N-terminal of IGFBP3, especially the IGF
      binding site, plays an important role in interacting with ALS as well as in
      stabilizing the dual complex, independent of IGFs.

PMID- 15469691
TI  - Identification and characterization of a novel angiostatin-binding protein by the
      display cloning method.
AB  - Angiostatin is a potent anti-angiogenic protein. To examine the angiostatin
      interacting proteins, we used the display-cloning method with a T7 phage library
      presenting human cDNAs. The specific T7 phage clone that bound to the immobilized
      angiostatin was isolated, and a novel gene encoding the displayed polypeptide on
      the isolated T7 phage was identified. The displayed angiostatin-binding sequence
      was expressed in E. coli as a soluble protein and purified to homogeneity. This
      novel angiostatin-binding region interacted specifically to angiostatin with a
      dissociation constant of 3.4 x 10(-7) M. A sequence analysis showed that the
      identified sequence was a part of the large ORF of 1,998 amino acids, whose
      function has not yet been characterized. A Northern analysis indicated that the
      gene containing the angiostatin-binding sequence was expressed differentially in
      the developmental stages or cell types.

PMID- 15469692
TI  - Increased DNA polymerase fidelity of the Lamivudine resistant variants of human
      hepatitis B virus DNA polymerase.
AB  - Although efficient antiviral lamivudine is used for HBV-infected patients, a
      prolonged treatment with nucleoside analogs often results in lamivudine-resistant
      variants. In this study, we evaluated the fidelity of the lamivudine-resistant
      variants. The FLAG-tagged wild-type (FPolE) and Met550 variants (FPolE/M550A,
      M550V, and M550I) of HBV DNA polymerases were expressed in insect cells, then
      purified. Like many other reverse transcriptases, no 3' --> 5' exonuclease
      activity was detected in the HBV DNA polymerase. Since there is no proofreading
      activity, then the use of the site-specific nucleotide misincorporation method is
      beneficial. From the f(ins) value analysis, it is evident that M550I and M550V
      exhibit higher fidelity values than the wild-type HBV DNA polymerase, while M550A
      exhibits similar fidelity values. It is therefore suggested that lamivudine
      resistance comes from the stringency to dNTP binding and the discrimination of
      dCTP and lamivudine in M550V and M550I.

PMID- 15469693
TI  - Molecular structure and organization of crustacean hyperglycemic hormone genes of
      Penaeus monodon.
AB  - The Crustacean hyperglycemic hormone (CHH) has been shown to exist as multiple
      molecular forms in several crustacean species. In Penaeus monodon, a gene
      encoding CHH (so-called Pem-CHH1) was recently described. In this study, the
      molecular structures of two other CHH genes (Pem-CHH2 and Pem-CHH3) are reported.
      Both the Pem-CHH2 and Pem-CHH3 genes contain three exons that are separated by
      two introns that are similar to the structure of other genes in the same family.
      An analysis of the upstream nucleotide sequences of each Pem-CHH gene has
      identified the putative promoter element (TATA box) and putative binding sites
      for several transcription factors. The binding sites for CREB, Pit-1, and AP-1
      were found upstream of all three Pem-CHH genes. A Southern blot analysis showed
      that at least one copy of each Pem-CHH gene was located within the same 10 kb
      genomic DNA fragment. These results suggest that the CHH genes are arranged in a
      cluster in the genome of P. monodon, and that their expression may be modulated
      by similar mechanisms.

PMID- 15469694
TI  - Protective role of tissue transglutaminase in the cell death induced by TNF-alpha
      in SH-SY5Y neuroblastoma cells.
AB  - Tissue transglutaminase (tTGase) regulates various biological processes,
      including extracellular matrix organization, cellular differentiation, and
      apoptosis. Here we report the protective role of tTGase in the cell death that is
      induced by the tumor necrosis factor alpha (TNF-alpha) and ceramide, a product of
      the TNF-alpha signaling pathway, in human neuroblastoma SH-SY5Y cells. Treatment
      with retinoic acid (RA) induced the differentiation of the neuroblastoma cells
      with the formation of extended neurites. Immunostaining and Western blot analysis
      showed the tTGase expression by RA treatment. TNF-alpha or C(2) ceramide, a cell
      permeable ceramide analog, induced cell death in normal cells, but cell death was
      largely inhibited by the RA treatment. The inhibition of tTGase by the tTGase
      inhibitors, monodansylcadaverine and cystamine, eliminated the protective role of
      RA-treatment in the cell death that is caused by TNF-alpha or C(2)-ceramide. In
      addition, the co-treatment of TNF-alpha and cycloheximide decreased the protein
      level of tTGase and cell viability in the RA-treated cells, supporting the role
      of tTGase in the protection of cell death. DNA fragmentation was also induced by
      the co-treatment of TNF-alpha and cycloheximide. These results suggest that
      tTGase expressed by RA treatment plays an important role in the protection of
      cell death caused by TNF-alpha and ceramide.

PMID- 15469695
TI  - Suppression of ceramide-induced cell death by hepatitis C virus core protein.
AB  - The hepatitis C virus (HCV) core protein is believed to be one of viral proteins
      that are capable of preventing virus-infected cell death upon various stimuli.
      But, the effect of the HCV core protein on apoptosis that is induced by various
      stimuli is contradictory. We examined the possibility that the HCV core protein
      affects the ceramide-induced cell death in cells expressing the HCV core protein
      through the sphingomyelin pathway. Cell death that is induced by C(2)-ceramide
      and bacterial sphingomyelinase was analyzed in 293 cells that constitutively
      expressed the HCV core protein and compared with 293 cells that were stably
      transfected only with the expression vector. The HCV core protein inhibited the
      cell death that was induced by these reagents. The protective effects of the HCV
      core protein on ceramide-induced cell death were reflected by the reduced
      expression of p21(WAF1/Cip1/Sid1) and the sustained expression of the Bcl-2
      protein in the HCV core-expressing cells with respect to the vector-transfected
      cells. These results suggest that the HCV core protein in 293 cells plays a role
      in the modulation of the apoptotic response that is induced by ceramide. Also,
      the ability of the HCV core protein to suppress apoptosis might have important
      implications in understanding the pathogenesis of the HCV infection.

PMID- 15469696
TI  - Purification and characterization of six fibrinolytic serine-proteases from
      earthworm Lumbricus rubellus.
AB  - The six lumbrokinase fractions (F1 to F6) with fibrinolytic activities were
      purified from earthworm Lumbricus rubellus lysates using the procedures of
      autolysis, ammonium sulfate fractionation, and column chromatography. The
      proteolytic activities on the casein substrate of the six iso-enzymes ranged from
      11.3 to 167.5 unit/mg with the rank activity orders of F2 > F1 > F5 > F6 > F3 >
      F4. The fibrinolytic activities of the six fractions on the fibrin plates ranged
      from 20.8 to 207.2 unit/mg with rank orders of F6 > F2 > F5 > F3 > F1 > F4. The
      molecular weights of each iso-enzyme, as estimated by SDS-PAGE, were 24.6 (F1),
      26.8 (F2), 28.2 (F3), 25.4 (F4), 33.1 (F5), and 33.0 kDa (F6), respectively. The
      plasminogen was activated into plasmin by the enzymes. The optimal temperature of
      the six iso-enzymes was 50 degrees C, and the optimal pH ranged from pH 4-12. The
      four iso-enzymes (F1-F4) were completely inhibited by PMSF. The two enzymes (F5
      and F6) were completely inhibited by aprotinin, TLCK, TPCK, SBTI, LBTI, and
      leupeptin. The N-terminal amino acid (aa) sequences of the first 20 to 22
      residues of each fraction had high homology. All six iso-enzymes had identical aa
      residues 2-3 and 13-15. The N-terminal 21-22 aa sequences of the F2, F3, and F4
      iso-enzymes were almost the same. The N-terminal aa sequences of F5 and F6 were
      identical.

PMID- 15469697
TI  - Identification, characterization and phylogenic analysis of conserved genes
      within the odvp-6e/odv-e56 gene region of Choristoneura fumiferana granulovirus.
AB  - The genes that are located within the odvp-6e/odv-e56 region of the Choristoneura
      fumiferana granulovirus (ChfuGV) were identified by sequencing the 11 kb BamHI
      restriction fragment on the ChfuGV genome. The global GC content that was
      calculated from the data obtained from this genomic region was 34.96%. The open
      reading frames (ORFs), located within the odvp-6e/odv-e56 region, are presented
      and compared to the equivalent ORFs that are located at the same region in other
      GVs. This region is composed of 14 ORFs, including three ORFs that are unique to
      ChfuGV with no obvious homologues in other baculoviruses as well as eleven ORFs
      with homologues to granuloviral ORFs, such as granulin, CfORF2, pk-1, ie-1, odv
      e18, p49, and odvp-6e/odv-e56. In this study, the conceptual products of seven
      major conserved ORFs (granulin, CfORF2, IE-1, ODV-E18, p49 and ODVP-6E/ODV-E56)
      were used in order to construct phylogenetic trees. Our results show that
      granuloviruses can be grouped in 2 distinct groups as follows: Group I;
      Choristoneura fumiferana granulovirus (ChfuGV), Cydia pomonella granulovirus
      (CpGV), Phthorimaea operculella granulovirus (PhopGV), and Adoxophyes orana
      granulovirus (AoGV). Group II; Xestia c-nigrum granulovirus (XcGV), Plutella
      xylostella granulovirus (PxGV), and Trichoplusia ni granulovirus (TnGV). The
      ChfuGV conserved proteins are most closely related to those of CpGV, PhopGV, and
      AoGV. Comparative studies, performed on gene arrangements within this region of
      genomes, demonstrated that three GVs from group I maintain similar gene
      arrangements.

PMID- 15469698
TI  - Species identification of the tropical abalone (Haliotis asinina, Haliotis ovina,
      and Haliotis varia) in Thailand using RAPD and SCAR markers.
AB  - A randomly amplified polymorphic DNA (RAPD) analysis was used to identify the
      species- and population-specific markers of abalone; Haliotis asinina, H. ovina,
      and H. varia in Thai waters. Fifteen species-specific and six population-specific
      RAPD markers were identified. In addition, an 1650 bp band (UBC195) that was
      restricted to H. ovina from the Gulf of Thailand (east) was also found. All of
      the specific RAPD markers were cloned and sequenced. Twenty pairs of primers were
      designed and specificity-tested (N = 12 and 4 for target and non-target species,
      respectively). Seven primer pairs (CUHA1, 2, 4, 11, 12, 13, and 14) were
      specifically amplified by H. asinina DNA, whereas a single pair of primers showed
      specificity with H. ovina (CUHO3) and H. varia (CUHV1), respectively. Four primer
      pairs, including CUHA2, CUHA12, CUHO3, and CUHV1, were further examined against
      216 individuals of abalone (N = 111, 73, and 32, respectively). Results indicated
      the species-specific nature of all of them, except CUHO3, with the sensitivity of
      detection of 100 pg and 20 pg of the target DNA template for CUHA2 and CUHA12 and
      CUHV1, respectively. The species-origin of the frozen, ethanol-preserved, dried,
      and boiled H. asinina specimens could also be successfully identified by CUHA2.

PMID- 15469699
TI  - Activity of some hepatic enzymes in schistosomiasis and concomitant alteration of
      arylsulfatase B.
AB  - The levels of arylsulfatases A and B, alpha-amylase, aspartate transcarbamylase,
      and gamma-glutamyl transpeptidase were investigated during the infection of mice
      with schistosoma mansoni. This infection caused a significant (p < 0.001)
      increase in the activity of hepatic arylsulfatase B (ASB), aspartate
      transcarbamylases and gamma-glutamyl transpeptidase. A non-significant difference
      occurred for alpha-amylase (p < 0.3) and arylsulfatase A (p > 0.5) when compared
      to the control. The specific activity of hepatic ASB was progressively increased
      with the progression of the Schistosoma-infection. Moreover, the kinetic studies
      of hepatic ASB in Schistosoma-infection showed that a slight decrease in the
      value of K(m) and about a 40% increase in V(max) when compared to the control. In
      addition, the pH optimum of hepatic ASB was altered from 6 to 7 as a result of
      schistosomiasis. These observations suggest that there are schistosomiasis
      associated changes of the catalytic and kinetic properties of hepatic ASB.

PMID- 15469700
TI  - Purification and partial characterization of a lectin from the fresh leaves of
      Kalanchoe crenata (Andr.) Haw.
AB  - A haemagglutinating protein from the saline extracts of Kalanchoe crenata leaves,
      which agglutinate all human blood types, was purified to homogeneity by ion
      exchange chromatography on a DEAE-Cellulose column followed by gel filtration on
      a Sephadex G-100 column. The purified protein showed one band, both in non
      denaturing PAGE and SDS-PAGE. The M(r) that was determined by SDS-PAGE was 44,000
      Da and that estimated from gel filtration was 47,000. Treatment of the
      haemagglutinating protein with 5 mM EDTA diminished the haemagglutinating
      activity to 50% of the original level. The addition of divalent cations, 10 mM
      Mg(2+), 10 mM Mn(2+), or 10mM Ba(2+), totally restored and enhanced the activity.
      The protein showed maximum activity over the 3-7 pH range and was heat-resistant.
      It was also a glycoprotein containing about 1.5% carbohydrate.

PMID- 15469701
TI  - Methylene tetrahydrofolate reductase C677T mutation and left ventricular
      hypertrophy in Turkish patients with type II diabetes mellitus.
AB  - This study was designed to investigate, in the Turkish population, the
      association of methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism
      and left ventricular hypertrophy (LVH) in patients with type II diabetes
      mellitus. Our study included 249 patients with type II diabetes mellitus (102
      men, 147 women) and 214 healthy volunteers as controls (91 men, 123 women). MTHFR
      C677T genotypes were determined by polymerase chain reaction, restriction
      fragment length polymorphism techniques. No differences were observed in the
      distribution of MTHFR genotypes or allele frequencies in the cases versus the
      controls. The frequency of the MTHFR-mutated allele (T) was 31.7% in the type II
      diabetes mellitus versus 31.1% of the controls. The homozygous mutation (T/T) in
      the MTHFR gene was identified in 12% of the type II diabetes mellitus versus 9.3%
      of the controls. Patients with the TT genotype showed a higher prevalence of LVH
      when compared to patients with the CC and CT genotypes (p = 0.01). The MTHFR gene
      C677T mutation may be a possible risk factor for the development of LVH in the
      type II diabetic patients.

PMID- 15469702
TI  - Pyruvate protection against endothelial cytotoxicity induced by blockade of
      glucose uptake.
AB  - We have previously demonstrated that the redox reactant pyruvate prevents
      apoptosis in the oxidant model of bovine pulmonary artery endothelial cells
      (BPAEC), and that the anti-apoptotic mechanism of pyruvate is mediated in part
      via the mitochondrial matrix compartment. However, cytosolic mechanisms for the
      cytoprotective feature of pyruvate remain to be elucidated. This study
      investigated the pyruvate protection against endothelial cytotoxicity when the
      glycolysis inhibitor 2-deoxy-D-glucose (2DG) was applied to BPAEC. Millimolar 2DG
      blocked the cellular glucose uptake in a concentration- and time-dependent manner
      with >85% inhibition at > or =5 mM within 24 h. The addition of 2DG evoked BPAEC
      cytotoxicity with a substantial increase in lipid peroxidation and a marked
      decrease in intracellular total glutathione. Exogenous pyruvate partially
      prevented the 2DG-induced cell damage with increasing viability of BPAEC by 25
      30%, and the total glutathione was also modestly increased. In contrast, 10 mM L
      lactate, as a cytosolic reductant, had no effect on the cytotoxicity and lipid
      peroxidation that are evoked by 2DG. These results suggest that 2DG toxicity may
      be a consequence of the diminished potential of glutathione antioxidant, which
      was partially restored by exogenous pyruvate but not L-lactate. Therefore,
      pyruvate qualifies as a cytoprotective agent for strategies that attenuate the
      metabolic dysfunction of the endothelium, and cellular glucose oxidation is
      required for the functioning of the cytosolic glutathione/NADPH redox system.

PMID- 15469703
TI  - Detection of germline mutations in argentine retinoblastoma patients: low and
      full penetrance retinoblastoma caused by the same germline truncating mutation.
AB  - Constitutional RB1 gene mutations were studied in a series of 21 families with
      unilateral and bilateral retinoblastoma patients. Peripheral blood lymphocytes
      were analyzed by "exon by exon" PCR-heteroduplex and sequencing. Mutations were
      identified in 6 (29%) of the patients. One mutation corresponded to an intronic
      polymorphism in g.174351T > A. The other five mutations resulted C to T exonic
      transitions, four were CGA sequences (g.65386, g.150037 in two patients, and
      g.162237), creating stop codons and presumably truncated proteins. The fifth one
      was new and resulted in alanine to valine substitution (g.73774). Two patients
      had the same the germline truncated mutation (g.150037C > T), one with a familial
      bilateral early onset retinoblastoma and one with a sporadic unilateral late
      onset retinoblastoma. The later type has not been previously described. This
      finding is discussed in the genotype/phenotype correlation context. Additionally,
      a single nucleotide change was found in six studied samples, where a C to T
      homozygous transversion was identified in intron 26 (IVS26 + 28). It is worthy
      the non concordance of the nucleotide with the published sequence. This analysis
      proved to be a useful method for the detection of mutations in the RB1 gene, and
      contributed to the adequate genetic counseling to patients and relatives.

PMID- 15469704
TI  - Cloning and sequencing analysis of the repressor gene of temperate
      mycobacteriophage L1.
AB  - The wild-type and temperature-sensitive (ts) repressor genes were cloned from the
      temperate mycobacteriophage L1 and its mutant L1cIts391, respectively. A
      sequencing analysis revealed that the 131st proline residue of the wild-type
      repressor was changed to leucine in the ts mutant repressor. The 100% identity
      that was discovered between the two DNA regions of phages L1 and L5, carrying the
      same sets of genes including their repressor genes, strengthened the speculation
      that L1 is a minor variant of phage L5 or vice versa. A comparative analysis of
      the repressor proteins of different mycobacteriophages suggests that the
      mycobacteriophage-specific repressor proteins constitute a new family of
      repressors, which were possibly evolved from a common ancestor. Alignment of the
      mycobacteriophage-specific repressor proteins showed at least 7 blocks
      (designated I-VII) that carried 3-8 identical amino acid residues. The amino acid
      residues of blocks V, VI, and some residues downstream to block VI are crucial
      for the function of the L1 (or L5) repressor. Blocks I and II possibly form the
      turn and helix 2 regions of the HTH motif of the repressor. Block IV in the L1
      repressor is part of the most charged region encompassing amino acid residues 72
      92, which flanks the putative N-terminal basic (residues 1-71) and C-terminal
      acidic (residues 93-183) domains of L1 repressor.

PMID- 15469705
TI  - Chemical modification of transducin with dansyl chloride hinders its binding to
      light-activated rhodopsin.
AB  - Transducin (T), the heterotrimeric guanine nucleotide binding protein in rod
      outer segments, serves as an intermediary between the receptor protein,
      rhodopsin, and the effector protein, cGMP phosphodiesterase. Labeling of T with
      dansyl chloride (DnsCl) inhibited its light-dependent guanine nucleotide binding
      activity. Conversely, DnsCl had no effect on the functionality of rhodopsin.
      Approximately 2-3 mol of DnsCl were incorporated per mole of T. Since
      fluoroaluminate was capable of activating DnsCl-modified T, this lysine-specific
      labeling compound did not affect the guanine nucleotide-binding pocket of T.
      However, the labeling of T with DnsCl hindered its binding to photoexcited
      rhodopsin, as shown by sedimentation experiments. Additionally, rhodopsin
      completely protected against the DnsCl inactivation of T. These results
      demonstrated the existence of functional lysines on T that are located in the
      proximity of the interaction site with the photoreceptor protein.

PMID- 15469706
TI  - New performance from an old member: SNP assay and de novo sequencing mediated by
      exo+ DNA polymerases.
AB  - DNA polymerases without the 3' exonuclease function (exo(-) pol) have been widely
      used in sequencing and SNP genotyping. As a major player that expedited the
      coming of the postgenomic era, exo(-) polymerases worked remarkably well in the
      Human Genome Sequencing Project. However, it has become a challenge for this
      class of polymerases to efficiently screen the large number of SNPs that are
      found in the human genome. For more than three decades it has been recognized
      that polymerase fidelity varied according to the presence of proofreading
      activity that is mediated by its internal 3' exonuclease. Polymerases with
      proofreading function are famous for their high fidelity in DNA replication both
      in vivo and in vitro, but this well-known class of polymerases has been almost
      completely neglected in genetic analysis in the postgenomic era. We speculate
      that exo(+) polymerases may exhibit higher nucleotide identification ability when
      compared to exo- polymerases for an in vitro genetic analysis. With the
      application of exo(+) polymerases in SNP assays, a novel mechanism for the
      maintenance of DNA replication, the on/off switch, was discovered. Two new SNP
      assays have been developed to carry out genome-wide genotyping, taking advantage
      of the enzymatic properties of exo(+) polymerases. Furthermore, the on/off switch
      mechanism embodies a powerful nucleotide identification ability, which can be
      used to discriminate the bases that are upstream of the 3' terminus, and thus
      defines a new concept in de novo sequencing technology. Application of exo(+)
      polymerases to genetic analysis, and especially SNP assays, will greatly
      accelerate the pace to personalized medicine.

PMID- 15469707
TI  - Presence of rhodanese in the cytosolic fraction of the fruit bat (Eidolon helvum)
      liver.
AB  - Rhodanese was isolated and purified from the cytosolic fraction of liver tissue
      homogenate of the fruit bat, Eidolon helvum, by using ammonium sulphate
      precipitation and CM-Sephadex C-50 ion exchange chromatography. The specific
      activity was increased 130-fold with a 53% recovery. The K(m) values for KCN and
      Na(2)S(2)O(3) as substrates were 13.5 +/- 2.2mM and 19.5 +/- 0.7 mM,
      respectively. The apparent molecular weight was estimated by gel filtration on a
      Sephadex G-100 column to be 36,000 Da. The optimal activity was found at a high
      pH (pH 9.0) and the temperature optimum was 35 degrees C. An Arrhenius plot of
      the heat stability data consisted of two linear segments with a break occurring
      at 35 degrees C. The apparent activation energy values from these slopes were
      11.5 kcal/mol and 76.6 kcal/mol. Inhibition studies on the enzyme with a number
      of cations showed that Mg(2+), Mn(2+), Ca(2+), and Co(2+) did not affect the
      activity of the enzyme, but Hg(2+) and Ba(2+) inhibited the enzyme.

PMID- 15469708
TI  - Isolation, characterization, and molecular cloning of the cDNA encoding a novel
      phytase from Aspergillus niger 113 and high expression in Pichia pastoris.
AB  - Phytases catalyze the release of phosphate from phytic acid. Phytase-producing
      microorganisms were selected by culturing the soil extracts on agar plates
      containing phytic acid. Two hundred colonies that exhibited potential phytase
      activity were selected for further study. The colony showing the highest phytase
      activity was identified as Aspergillus niger and designated strain 113. The
      phytase gene from A. niger 113 (phyI1) was isolated, cloned, and characterized.
      The nucleotide and deduced amino acid sequence identity between phyI1 and phyA
      from NRRL3135 were 90% and 98%, respectively. The identity between phyI1 and phyA
      from SK-57 was 89% and 96%. A synthetic phytase gene, phyI1s, was synthesized by
      successive PCR and transformed into the yeast expression vector carrying a signal
      peptide that was designed and synthesized using P. pastoris biased codon. For the
      phytase expression and secretion, the construct was integrated into the genome of
      P. pastoris by homologous recombination. Over-expressing strains were selected
      and fermented. It was discovered that ~4.2 g phytase could be purified from one
      liter of culture fluid. The activity of the resulting phytase was 9.5 U/mg. Due
      to the heavy glycosylation, the expressed phytase varied in size (120, 95, 85,
      and 64 kDa), but could be deglycosylated to a homogeneous 64 kDa species. An
      enzymatic kinetics analysis showed that the phytase had two pH optima (pH 2.0 and
      pH 5.0) and an optimum temperature of 60 degrees C.

PMID- 15469709
TI  - Aromaticity of Tyr-202 in the alpha4-alpha5 loop is essential for toxicity of the
      Bacillus thuringiensis Cry4A toxin.
AB  - The current model for the mechanism of action of the Bacillus thuringiensis Cry
      delta-endotoxins involves the penetration of the alpha4-alpha5 hairpin into the
      target midgut epithelial cell membranes, followed by pore formation. In this
      study, PCR-based mutagenesis was employed to identify a critical residue within
      the alpha4-alpha5 loop of the 130kDa Cry4A mosquito-larvicidal protein. Alanine
      substitutions of two charged (Asp-198 and Asp-200) and four polar (Asn-190, Asn
      195, Tyr-201 and Tyr-202) residues in the alpha4-alpha5 loop were performed. Like
      the wild-type, all of the mutant toxins were over-expressed as inclusion bodies
      in Escherichia coli. When E. coli cells expressing each mutant toxin were
      bioassayed against Aedes aegypti larvae, larvicidal activity was completely
      abolished for the substitution of only Tyr-202, while replacements at the other
      positions still retained a high level of toxicity. Further replacement of Tyr-202
      with an aromatic side chain, phenylalanine, did not affect the toxicity. These
      results revealed a crucial role in toxin activity for the conserved aromatic
      residue at the 202 position within the alpha4-alpha5 loop of the Cry4A toxin.

PMID- 15469710
TI  - Nano-scale proteomics approach using two-dimensional fibrin zymography combined
      with fluorescent SYPRO ruby dye.
AB  - In general, a SYPRO Ruby dye is well known as a sensitive fluorescence-based
      method for detecting proteins by one-or two-dimensional SDS-PAGE (1-DE or 2-DE).
      Based on the SYPRO Ruby dye system, the combined two-dimensional fibrin
      zymography (2-D FZ) with SYPRO Ruby staining was newly developed to identify the
      Bacillus sp. proteases. Namely, complex protein mixtures from Bacillus sp. DJ-4,
      which were screened from Doen-Jang (Korean traditional fermented food), showed
      activity on the zymogram gel. The gel spots on the SYPRO Ruby gel, which
      corresponded to the active spots showing on the 2-D FZ gel, were analyzed by a
      matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass
      spectrometric analysis. Five intracellular fibrinolytic enzymes of Bacillus sp.
      DJ-4 were detected through 2-D FZ. The gel spots on the SYPRO Ruby dye stained 2
      D gel corresponding to 2-D FZ were then analyzed by MALID-TOF MS. Three of the
      five gel spots proved to be quite similar to the ATP-dependent protease,
      extracellular neutral metalloprotease, and protease of Bacillus subtilis. Also,
      the extracellular proteases of Bacillus sp. DJ-4 employing this combined system
      were identified on three gels (e.g., casein, fibrin, and gelatin) and the
      proteolytic maps were established. This combined system of 2-D zymography and
      SYPRO Ruby dye should be useful for searching the specific protease from complex
      protein mixtures of many other sources (e.g., yeast and cancer cell lines).

PMID- 15469711
TI  - Bacillus thuringiensis Cry4A and Cry4B mosquito-larvicidal proteins: homology
      based 3D model and implications for toxin activity.
AB  - Three-dimensional (3D) models for the 65-kDa activated Cry4A and Cry4B delta
      endotoxins from Bacillus thuringiensis subsp. israelensis that are specifically
      toxic to mosquito-larvae were constructed by homology modeling, based on atomic
      coordinates of the Cry1Aa and Cry3Aa crystal structures. They were structurally
      similar to the known structures, both derived 3D models displayed a three-domain
      organization: the N-terminal domain (I) is a seven-helix bundle, while the middle
      and C-terminal domains are primarily comprise of anti-parallel beta-sheets.
      Circular dichroism spectroscopy confirmed the secondary structural contents of
      the two homology-based Cry4 structures. A structural analysis of both Cry4 models
      revealed the following: (a) Residues Arg-235 and Arg-203 are located in the
      interhelical 5/6 loop within the domain I of Cry4A and Cry4B, respectively. Both
      are solvent exposed. This suggests that they are susceptible to tryptic cleavage.
      (b) The unique disulphide bond, together with a proline-rich region within the
      long loop connecting alpha4 and alpha5 of Cry4A, were identified. This implies
      their functional significance for membrane insertion. (c) Significant structural
      differences between both models were found within domain II that may reflect
      their different activity spectra. Structural insights from this molecular
      modeling study would therefore increase our understanding of the mechanic aspects
      of these two closely related mosquito-larvicidal proteins.

PMID- 15469712
TI  - Characterization of monoclonal antibodies against heavy and light chains of
      flounder (Paralichthys olivaceus) immunoglobulin.
AB  - Flounder (Paralichthys olivaceus) Immunoglobulins (Igs) were purified from the
      serum of mouse IgG-immunized flounder by using affinity chromatography. Under
      denaturing conditions in SDS-PAGE, the flounder Igs appeared to be composed of 2
      heavy (H) chains (72 and 77 kDa) and two light (L) chains (26 and 28 kDa).
      Monoclonal antibodies (MAbs) were produced by the fusion of myeloma cells (SP2/0)
      with Balb/c mouse spleen cells that were previously sensitized against affinity
      purified flounder Igs. In a Western blot analysis, the produced MAbs, FIM511,
      FIM519, and FIM562 recognized both the 72 and 77 kDa H chains, 26 kDa, and 28 kDa
      L chain, respectively. Mouse antiserum against flounder Igs reacted more strongly
      with the L chain of 28 kDa than with 26 kDa, suggesting that the 28 kDa molecule
      is more immunogenic than the 26 kDa L chain molecule. In a FACS analysis, the
      ratios of the Ig+ cell population in the flounder head kidney and spleen cells
      were 49% and 24%, respectively. Unexpectedly, however, the ratios of the Ig+ B
      like cell population in the flounder were not significantly augmented, even after
      the immunization of an immunogenic antigen. This suggests that the humoral immune
      response in fish could be considerably different from that in mammals. The
      produced MAbs in this study would be useful in characterizing flounder Ig+ B-like
      cells and in developing flounder Ig detecting an immunoassay system.

PMID- 15469713
TI  - Homeodomain-leucine zipper proteins interact with a plant homologue of the
      transcriptional co-activator multiprotein bridging factor 1.
AB  - StMBF1 (Solanum tuberosum multiprotein bridging factor 1) is a plant member of
      the MBF1 family of transcriptional co-activators. In an attempt to understand the
      role of StMBF1, we analyzed its interaction with plant transcription factors of
      the homeodomain-leucine zipper (Hd-Zip) family, a group of proteins with a
      typical leucine zipper motif adjacent to a homeodomain. StMBF1 is able to
      interact in vitro with the Hd-Zip protein Hahb-4 both in the presence and absence
      of DNA. Upon binding, StMBF1 increases the DNA binding affinity of Hahb-4, and of
      another plant homeodomain containing protein from the GL2/Hd-Zip IV family, HAHR
      1. The biological role of interactions is discussed in this paper.

PMID- 15469714
TI  - Modification of Cu,Zn-superoxide dismutase by oxidized catecholamines.
AB  - Oxidation of catecholamines may contribute to the pathogenesis of Parkinson's
      disease (PD). The effect of the oxidized products of catecholamines on the
      modification of Cu,Zn-superoxide dismutase (SOD) was investigated. When Cu,Zn-SOD
      was incubated with the oxidized 3,4-dihydroxyphenylalanine (DOPA) or dopamine,
      the protein was induced to be aggregated. The deoxyribose assay showed that
      hydroxyl radicals were generated during the oxidation of catecholamines in the
      presence of copper ion. Radical scavengers, azide, N-acetylcysteine, and catalase
      inhibited the oxidized catecholamine-mediated Cu,Zn-SOD aggregation. Therefore,
      the results indicate that free radicals may play a role in the aggregation of
      Cu,Zn-SOD. When Cu,Zn-SOD that had been exposed to catecholamines was
      subsequently analyzed by an amino acid analysis, the glycine and histidine
      residues were particularly sensitive. These results suggest that the modification
      of Cu,Zn-SOD by oxidized catecholamines might induce the perturbation of cellular
      antioxidant systems and led to a deleterious cell condition.

PMID- 15469715
TI  - Modification of substrate inhibition of synaptosomal acetylcholinesterase by
      cardiotoxins.
AB  - Different types of cardiotoxin (I-V and n) were isolated and purified from the
      venom of the Taiwan cobra (Naja naja atra). The effects of these cardiotoxins
      were studied on membrane-bound acetylcholinesterase, which was isolated from a
      sheep's brain cortex. The results showed that cardiotoxins I-III, V, and n
      activated the enzyme by modification of substrate inhibition, but cardiotoxin
      IV's reaction was different. The inhibition and activation of
      acetylcholinesterase were linked to the functions of the hydrophobicity index,
      presence of a cationic cluster, and the accessible arginine residue. Our results
      indicate that Cardiotoxins have neither a cationic cluster nor an arginine
      residue in their surface area of loop I; therefore, in contrast to fasciculin,
      cardiotoxins are attached by loop II to the peripheral site of the enzyme. As a
      result, fasciculin seems to stabilize nonfunctional conformation, but
      cardiotoxins seem to stabilize the functional conformation of the enzyme. Based
      on our experimental and theoretical findings, similar secondary and tertiary
      structures of cardiotoxins and fasciculin seem to have an opposite function once
      they interact with acetylcholinesterase.

PMID- 15469716
TI  - Localization of germin genes and their products in developing wheat coleoptiles.
AB  - Germination is a process which characterized with nescient synthesis of genes.
      Among the genes synthesized during the germination of wheat embryos, germin
      genes, proteins and their enzymatic activity were defined. Germin is a water
      soluble homopentameric glycoprotein which is remarkable resistant to degradation
      by a broad range of proteases including pepsin. Germin proteins found to have
      strong oxalate oxidase activity which produces hydrogen peroxide by degrading
      oxalic acid. The current study, aimed to localize the germin genes, proteins and
      enzymatic activities in developing coleoptiles which is a rapidly growing
      protective tissue of leaf primordium and shoot apex. Non-radioactively labeled
      germin riboprobes were employed to localize germin mRNAs in situ. FITC
      (Fluorescein isothiocyanate) and alkaline phosphatase linked anti-germin
      antibodies were used to localize germin proteins under the fluorescence and light
      microscopy and finally germin enzymatic activity was localized by using
      appropriate enzyme assay. The results revealed that in coleoptiles germin genes,
      proteins and their enzymatic activity were predominantly associated with the
      cells of epidermis and vascular bundle sheath cells.

PMID- 15469717
TI  - Molecular characterization of a thiJ-like gene in Chinese cabbage.
AB  - A cDNA clone for a salicylic acid-induced gene in Chinese cabbage (Brassica rapa
      subsp. pekinensis) was isolated and characterized. The cabbage gene encoding a
      protein of 392 amino acids contained a tandem array of two thiJ-like sequences.
      ThiJ is a thiamin biosynthesis enzyme that catalyzes the phosphorylation of
      hydroxymethylpyrimidine (HMP) to HMP monophosphate. Although the cabbage gene
      shows a similarity to bacterial thiJ genes, it also shares a similarity with the
      human DJ-1, a multifunctional protein that is involved in transcription
      regulation, male fertility, and parkinsonism. The cabbage thiJ-like gene is
      strongly induced by salicylic acid and a nonhost pathogen, Pseudomonas syringae
      pv. tomato, which elicits a hypersensitive response in Chinese cabbage. Treatment
      of the cabbage leaves with BTH, methyl jasmonate, or ethephon showed that the
      cabbage thiJ-like gene expression is also strongly induced by BTH, but not by
      methyl jasmonate or ethylene. This indicates that the cabbage gene is activated
      via a salicylic acid-dependent signaling pathway. Examination of the tissue
      specific expression revealed that the induction of the cabbage gene expression by
      BTH occurs in the leaf, stem, and floral tissues but not in the root.

PMID- 15469718
TI  - Rapid preparation of total nucleic acids from E. coli for multi-purpose
      applications.
AB  - Separate protocols are commonly used to prepare plasmid DNA, chromosomal DNA, or
      total RNA from E. coli cells. Various methods for the rapid preparation of
      plasmid DNA have been developed previously, but the preparation of the
      chromosomal DNA and total RNA are usually laborious. We report here a simple,
      fast, reliable, and cost-effective method to extract total nucleic acids from E.
      coli by direct lysis of the cells with phenol. Five distinct and sharp bands,
      which correspond to chromosomal DNA, plasmid DNA, 23S rRNA, 16S rRNA, and a
      mixture of small RNA, were observed when analyzing the prepared total nucleic
      acids on a regular 1-2% agarose gel. The simple and high-quality preparation of
      the total nucleic acids in a single tube allowed us to rapidly screen the
      recombinant plasmid, as well as to simultaneously monitor the change of the
      plasmid copy number and rRNA levels during the growth of E. coli in the liquid
      medium.

PMID- 15469719
TI  - DNA microarray probe preparation by gel isolation nested PCR.
AB  - To develop a simplified method that can rapidly prepare DNA microarray probes in
      a massive scale, a lambda phage genomic DNA-fragments library was constructed for
      the microarray-probes collection. Four methods of DNA band recovery from the
      first PCR products were tested and compared. The DNA microarray probes were
      collected by a novel method of nested PCR that was mediated by gel isolation of
      the first PCR products. This method was named GIN-PCR. The probes that were
      prepared by this GIN-PCR technique were used as subjects to fabricate a DNA
      microarray. The results showed that a wooden toothpick was superior to the other
      3 methods, since this technique can steadily transfer the DNA bands as the
      template of the second PCR after the first PCR. A group of probes were
      successfully collected and DNA microarrays were constructed using these probes.
      Hybridization results demonstrated that this technique of DNA recovery and probe
      preparation was rapid, efficient, and effective. We developed a cost-effective
      and less labor-intensive method for DNA microarray probe preparation by nested
      PCR that is mediated by wooden toothpick transfer of the DNA bands in the gel
      after electrophoresis.

PMID- 15469720
TI  - Sorting of the human folate receptor in MDCK cells.
AB  - The human folate receptor (hFR) is a glycosylphosphatidy-linositol (GPI) linked
      plasma membrane protein that mediates delivery of folates into cells. We studied
      the sorting of the hFR using transfection of the hFR cDNA into MDCK cells. MDCK
      cells are polarized epithelial cells that preferentially sort GPI-linked proteins
      to their apical membrane. Unlike other GPI-tailed proteins, we found that in MDCK
      cells, hFR is functional on both the apical and basolateral surfaces. We verified
      that the same hFR cDNA that transfected into CHO cells produces the hFR protein
      that is GPI-linked. We also measured the hFR expression on the plasma membrane of
      type III paroxysmal nocturnal hemoglobinuria (PNH) human erythrocytes. PNH is a
      disease that is characterized by the inability of cells to express membrane
      proteins requiring a GPI anchor. Despite this defect, and different from other
      GPI-tailed proteins, we found similar levels of hFR in normal and type III PNH
      human erythrocytes. The results suggest the hypothesis that there may be multiple
      mechanisms for targeting hFR to the plasma membrane.

PMID- 15469721
TI  - Protective effect of soybean against hepatocarcinogenesis induced by DL
      ethionine.
AB  - There has been increasing interest in the value of using soybean to delay or
      reduce the tumor incidence. This study was undertaken to investigate the possible
      protective effects of soybean against hepatocarcinogenesis induced by DL
      ethionine. Accordingly, we measured biochemical changes occurring in serum and
      liver of rats treated with DL-ethionine in the presence or absence of soybean.
      Male albino rats were fed a control diet containing the hepatocarcinogen, DL
      ethionine, or the control diet plus soybean 30%, or the control diet plus soybean
      plus DL-ethionine 0.25% for three months and then returned to a control diet for
      up to nine months. Rats fed a control diet plus DL-ethionine showed a gradual
      decrease in liver DNA, RNA, total protein, and liver weight and enzyme activities
      of liver transaminases (GOT and GPT) and alkaline phosphatase over the 7-month
      study period. This was followed by a large increase in the liver parameters at
      the end of the 9(th) month, except for 5'-nucleotidase and glucose-6-phosphatase
      that showed a large decrease. On the other hand, a gradual increase in the serum
      enzyme activities of GOT, GPT, 5-nucleotidase, alkaline phosphatase, and in the
      albumin/globulin (A/G) ratio is observed in the group of rats fed a control diet
      plus DL-ethionine compared to the control group over 8 months, and this was
      followed by a large increase in all serum parameters studied at nine-months. The
      administration of 30% soybean to the rat diet in addition to DL-ethionine
      maintained all parameters studied at near control values until the end of the
      9(th) month. This study suggests that soybean has a protective effect against the
      hepatocarcinogenesis induced by DL-ethionine.

PMID- 15469722
TI  - Efficient transduction with recombinant adenovirus in EBV-transformed B
      lymphoblastoid cell lines.
AB  - The Epstein-Barr-transformed B lymphoblastoid cell lines, LCL, which express
      antigens, are potential antigen-presenting cells (APCs) for the induction of
      cytotoxic T lymphocytes in vitro. However, transfecting LCL with subsequent
      selection by antibiotics is notoriously difficult because the plating
      efficiencies of LCL are reported to be 1% or less. Therefore, this study
      investigated the optimal conditions for increasing the transduction efficiency of
      a recombinant adenovirus to LCL for use as a source of APCs. The transduction
      efficiencies were < 13% (SD +/- 2.13) at a multiplicity of infection (MOI) of
      100, while it was increased to 28% (SD +/- 9.43) at an MOI of 1000. Moreover, its
      efficiencies to LCL that expressed the coxsackie adenovirus receptor were
      increased to 60% (SD +/- 6.35) at an MOI of 1000, and were further increased to
      70% (SD +/- 4.56) when combined with the centrifugal method. The cationic
      liposome or anionic polymer had no effect on the transduction efficiency when
      compared to that of the centrifugal method. These results may be used as a
      convenient source of target cells for a CTL assay and/or autologous APCs for the
      induction of the in vitro CTL responses that are specific to viral and tumor
      antigens.

PMID- 15469723
TI  - Inhibition of herpesvirus-6B RNA replication by short interference RNAs.
AB  - RNA interference (RNAi) is a process of sequence-specific gene silencing, which
      is initiated by double-stranded RNA (dsRNA). RNAi may also serve as an antiviral
      system in vertebrates. This study describes the inhibition of herpesvirus-6B (HHV
      6B) replication by short interference RNAs (siRNAs) that are targeted to the U38
      sequence that encodes DNA polymerase. When virus-infected SupT1 cells were
      treated by siRNA, these cells blocked the cytopathic effect (CPE) and detected
      the HHV-6B antibody-negative in indirect immunofluorescence assays (IFA). Our
      result suggests that RNAi can efficiently block Herpesvirus-6B replication.

PMID- 15469724
TI  - Production, isolation, and purification of L-asparaginase from Pseudomonas
      aeruginosa 50071 using solid-state fermentation.
AB  - The L-asparaginase (E. C. 3. 5. 1. 1) enzyme was purified to homogeneity from
      Pseudomonas aeruginosa 50071 cells that were grown on solid-state fermentation.
      Different purification steps (including ammonium sulfate fractionation followed
      by separation on Sephadex G-100 gel filtration and CM-Sephadex C50) were applied
      to the crude culture filtrate to obtain a pure enzyme preparation. The enzyme was
      purified 106-fold and showed a final specific activity of 1900 IU/mg with a 43%
      yield. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of
      the purified enzyme revealed it was one peptide chain with M(r) of 160 kDa. A
      Lineweaver-Burk analysis showed a K(m) value of 0.147 mM and V(max) of 35.7 IU.
      The enzyme showed maximum activity at pH 9 when incubated at 37 degrees C for 30
      min. The amino acid composition of the purified enzyme was also determined.

PMID- 15469725
TI  - Understanding enzyme structure and function in terms of the shifting specificity
      model.
AB  - The purpose of this paper is to suggest that the prominence of Haldane's
      explanation for enzyme catalysis significantly hinders investigations in
      understanding enzyme structure and function. This occurs despite the existence of
      much evidence that the Haldane model cannot embrace. Some of the evidence, in
      fact, disproves the model. A brief history of the explanation of enzyme catalysis
      is presented. The currently accepted view of enzyme catalysis--the Haldane model-
      is examined in terms of its strengths and weaknesses. An alternate model for
      general enzyme catalysis (the Shifting Specificity model) is reintroduced and an
      assessment of why it may be superior to the Haldane model is presented. Finally,
      it is proposed that a re-examination of many current aspects in enzyme structure
      and function (specifically, protein folding, x-ray and NMR structure analyses,
      enzyme stability curves, enzyme mimics, catalytic antibodies, and the loose
      packing of enzyme folded forms) in terms of the new model may offer crucial
      insights.

PMID- 15469726
TI  - Human liver specific transcriptional factor TCP10L binds to MAD4.
AB  - A human gene T-complex protein 10 like (TCP10L) was cloned in our lab. A previous
      study showed that it expressed specifically in the liver and testis. A
      transcription experiment revealed that TCP10L was a transcription factor with
      transcription inhibition activity. In this study, the human MAD4 was identified
      to interact with TCP10L by a yeast two-hybrid screen. This finding was confirmed
      by immunoprecipitation and subcellular localization experiments. As MAD4 is a
      member of the MAD family, which antagonizes the functions of MYC and promotes
      cell differentiation, the biological function of the interaction between TCP10L
      and MAD4 may be to maintain the differentiation state in liver cells. Also, we
      propose that the up-regulation of Myc is caused by the down-regulation of TCP10L
      in human hepatocarcinomas.

PMID- 15469727
TI  - Expression of cyclodextrinase gene from Paenibacillus sp. A11 in Escherichia coli
      and characterization of the purified cyclodextrinase.
AB  - The expression of the Paenibacillus sp. A11 cyclodextrinase (CDase) gene using
      the pUC 18 vector in Escherichia coli JM 109 resulted in the formation of an
      insoluble CDase protein in the cell debris in addition to a soluble CDase protein
      in the cytoplasm. Unlike the expression in Paenibacillus sp. A11, CDase was
      primarily observed in cytoplasm. However, by adding 0.5 M sorbitol as an
      osmolyte, the formation of insoluble CDase was prevented while a three-fold
      increase in cytoplasmic CDase activity was achieved after a 24 h-induction. The
      recombinant CDase protein was purified to approximately 14-fold with a 31%
      recovery to a specific activity of 141 units/mg protein by 40-60% ammonium
      sulfate precipitation, DEAE-Toyopearl 650 M, and Phenyl Sepharose CL-4B
      chromatography. It was homogeneous by non-denaturing and SDS-PAGE. The enzyme was
      a single polypeptide with a molecular weight of 80 kDa, as determined by gel
      filtration and SDS-PAGE. It showed the highest activity at pH 7.0 and 40 degrees
      C. The catalytic efficiency (k(cat)/K(m)) values for alpha-, beta-, and gamma- CD
      were 3.0 x 10(5), 8.8 x 10(5), and 5.5 x 10(5) M(-1) min(-1), respectively. The
      enzyme hydrolyzed CDs and linear maltooligosaccharides to yield maltose and
      glucose with less amounts of maltotriose and maltotetraose. The rates of
      hydrolysis for polysaccharides, soluble starch, and pullulan were very low. The
      cloned CDase was strongly inactivated by N-bromosuccinimide and
      diethylpyrocarbonate, but activated by dithiothreitol. A comparison of the
      biochemical properties of the CDases from Paenibacillus sp. A11 and E. coli
      transformant (pJK 555) indicates that they were almost identical.

PMID- 15469728
TI  - Antioxidant activity of NADH and its analogue--an in vitro study.
AB  - The antioxidant activities of NADH and of its analogue, 1,4-dihydro-2,6-dimethyl
      3,5-dicarbethoxy-pyridine (PyH(2)), were evaluated in vitro. NADH was found to be
      oxidized by the peroxyl radical derived from 2,2-azobis-(2-amidinopropane)
      dihydrochloride (AAPH) decomposition, in a pH-dependent manner. Both NADH and
      PyH(2) inhibited the peroxidation of egg yolk lecithin (EYL) liposomes, although
      PyH(2) was more effective than NADH when 2,2'-azobis-4-methoxy-2,4-dimethyl
      valeronitrile (methoxy-AMVN) was employed to induce EYL liposome peroxidation.
      The antioxidant activities of NADH and PyH(2) were also evaluated by measuring
      their influences on 1,3-diphenylisobenzofuran (DPBF) fluorescence decay in the
      presence of peroxyl radicals. NADH and PyH(2) were much more effective at
      inhibiting DPBF quenching in Triton X-100 micelles than in liposomes. These
      results indicate that NADH can inhibit lipid peroxidation despite being
      hydrophilic. Nevertheless, membrane penetration is an important factor and limits
      its antioxidant activity.

PMID- 15469729
TI  - Degradation of raw starch granules by alpha-amylase purified from culture of
      Aspergillus awamori KT-11.
AB  - Raw-starch-digesting alpha-amylase (Amyl III) was purified to an
      electrophoretically pure state from the extract of a koji culture of Aspergillus
      awamori KT-11 using wheat bran in the medium. The purified Amyl III digested not
      only soluble starch but also raw corn starch. The major products from the raw
      starch using Amyl III were maltotriose and maltose, although a small amount of
      glucose was produced. Amyl III acted on all raw starch granules that it has been
      tested on. However, it was considered that the action mode of the Amyl III on
      starch granules was different from that of glucoamylase judging from the
      observation of granules under a scanning electron microscope before and after
      enzyme reaction, and also from the reaction products. Glucoamylase (GA I) was
      also isolated and it was purified to an electrophoretically pure state from the
      extract. It was found that the electron micrographic features of the granules
      after treatment with the enzymes were quite different. A synergistic effect of
      Amyl III and GA I was observed for the digestion of raw starch granules.

PMID- 15469730
TI  - Molecular cloning and determination of the nucleotide sequence of raw starch
      digesting alpha-amylase from Aspergillus awamori KT-11.
AB  - Complementary DNAs encoding alpha-amylases (Amyl I, Amyl III) and glucoamylase
      (GA I) were cloned from Aspergillus awamori KT-11 and their nucleotide sequences
      were determined. The sequence of Amyl III that was a raw starch digesting alpha
      amylase was found to consist of a 1,902 bp open reading frame encoding 634 amino
      acids. The signal peptide of the enzyme was composed of 21 amino acids. On the
      other hand, the sequence of Amyl I, which cannot act on raw starch, consisted of
      a 1,500 bp ORF encoding 499 amino acids. The signal peptide of the enzyme was
      composed of 21 amino acids. The sequence of GA I consisted of a 1,920 bp ORF that
      encoded 639 amino acids. The signal peptide was composed of 24 amino acids. The
      amino acid sequence of Amyl III from the N-terminus to the amino acid number 499
      showed 63.3% homology with Amyl I. However, the amino acid sequence from the
      amino acid number 501 to C-terminus, including the raw-starch-affinity site and
      the TS region rich in threonine and serine, showed 66.9% homology with GA I.

PMID- 15469731
TI  - Comparison of hybridization behavior between double and single strands of targets
      and the application of asymmetric PCR targets in cDNA microarray.
AB  - Double stranded targets on the cDNA microarray contain representatives of both
      the coding and noncoding strands, which will introduce hybridization competition
      with probes. Here, the effect of double and single strands of targets on the
      signal intensity and the ratios of Cy5/Cy3 within the same slide were compared.
      The results show that single stranded targets can increase the hybridization
      efficiency without changing the Cy5/Cy3 ratio. Based on these results, a new
      strategy was established by generating cDNA targets with asymmetric PCR, instead
      of conventional PCR, to increase the sensitivity of the cDNA microarray.
      Furthermore, the feasibility of this approach was validated. The results indicate
      that the cDNA microarray system based on asymmetric PCR is more sensitive, with
      no decrease in the reliability and reproducibility as compared with that based on
      conventional symmetric PCR.

PMID- 15469732
TI  - Abrin induces HeLa cell apoptosis by cytochrome c release and caspase activation.
AB  - We identified apoptosis as being a significant mechanism of toxicity following
      the exposure of HeLa cell cultures to abrin holotoxin, which is in addition to
      its inhibition of protein biosynthesis by N-glycosidase activity. The treatment
      of HeLa cell cultures with abrin resulted in apoptotic cell death, as
      characterized by morphological and biochemical changes, i.e., cell shrinkage,
      internucleosomal DNA fragmentation, the occurrence of hypodiploid DNA, chromatin
      condensation, nuclear breakdown, DNA single strand breaks by TUNEL assay, and
      phosphatidylserine (PS) externalization. This apoptotic cell death was
      accompanied by caspase-9 and caspase-3 activation, as indicated by the cleavage
      of caspase substrates, which was preceded by mitochondrial cytochrome c release.
      The broad-spectrum caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl
      ketone (zVADfmk), prevented abrin-triggered caspase activation and partially
      abolished apoptotic cell death, but did not affect mitochondrial cytochrome c
      release. These results suggest that the release of mitochondrial cytochrome c,
      and the sequential caspase-9 and caspase-3 activations are important events in
      the signal transduction pathway of abrin-induced apoptotic cell death in the HeLa
      cell line.

PMID- 15469733
TI  - Mitochondrial damage and metabolic compensatory mechanisms induced by hyperoxia
      in the U-937 cell line.
AB  - Experimental hyperoxia represents a suitable in vitro model to study some
      pathogenic mechanisms related to oxidative stress. Moreover, it allows the
      investigation of the molecular pathophysiology underlying oxygen therapy and
      toxicity. In this study, a modified experimental set up was adopted to accomplish
      a model of moderate hyperoxia (50% O(2), 96 h culture) to induce oxidative stress
      in the human leukemia cell line, U-937. Spectrophotometric measurements of
      mitochondrial respiratory enzyme activities, NMR spectroscopy of culture media,
      determination of antioxidant enzyme activities, and cell proliferation and
      differentiation assays were performed. The data showed that moderate hyperoxia in
      this myeloid cell line causes: i) intriguing alterations in the mitochondrial
      activities at the levels of succinate dehydrogenase and succinate-cytochrome c
      reductase; ii) induction of metabolic compensatory adaptations, with significant
      shift to glycolysis; iii) induction of different antioxidant enzyme activities;
      iv) significant cell growth inhibition and v) no significant apoptosis. This work
      will permit better characterization the mitochondrial damage induced by
      hyperoxia. In particular, the data showed a large increase in the succinate
      cytochrome c reductase activity, which could be a fundamental pathogenic
      mechanism at the basis of oxygen toxicity.

PMID- 15469734
TI  - Structural design and characterization of a channel-forming peptide.
AB  - A 16-residue polypeptide model with the sequence acetyl-YALSLAATLLKEAASL-OH was
      derived by rational de novo peptide design. The designed sequence consists of
      amino acid residues with high propensity to adopt an alpha helical conformation,
      and sequential order was arranged to produce an amphipathic surface. The designed
      sequence was chemically synthesized using a solid-phase method and the
      polypeptide was purified by reverse-phase liquid chromatography. Molecular mass
      analysis by electro-spray ionization mass spectroscopy confirmed the correct
      designed sequence. Structural characterization by circular dichroism spectroscopy
      demonstrated that the peptide adopts the expected alpha helical conformation in
      50% acetonitrile solution. Liposome binding assay using Small Unilamellar Vesicle
      (SUV) showed a marked release of entrapped glucose by interaction between the
      lipid membrane and the tested peptide. The channel-forming activity of the
      peptide was revealed by a planar lipid bilayer experiment. An analysis of the
      conducting current at various applied potentials suggested that the peptide forms
      a cationic ion channel with an intrinsic conductance of 188 pS. These results
      demonstrate that a simple rational de novo design can be successfully employed to
      create short peptides with desired structures and functions.

PMID- 15469735
TI  - Purification and characterization of an acid deoxyribonuclease from the cultured
      mycelia of Cordyceps sinensis.
AB  - A new acid deoxyribonuclease (DNase) was purified from the cultured mycelia of
      Cordyceps sinensis, and designated CSDNase. CSDNase was purified by
      (NH(4))(2)SO(4) precipitation, Sephacryl S-100 HR gel filtration, weak anion
      exchange HPLC, and gel filtration HPLC. The protein was single-chained, with an
      apparent molecular mass of ca. 34 kDa, as revealed by SDS-PAGE, and an
      isoelectric point of 7.05, as estimated by isoelectric focusing. CSDNase acted on
      both double-stranded (ds) and single- stranded (ss) DNA, but preferentially on
      dsDNA. The optimum pH of CSDNase was pH 5.5 and its optimum temperature 55. The
      activity of CSDNase was not dependent on divalent cations, but its enzymic
      activity was inhibited by high concentration of the cation: MgCl(2) above 150 mM,
      MnCl(2) above 200 mM, ZnCl(2) above 150 mM, CaCl(2) above 200 mM, NaCl above 300
      mM, and KCl above 300 mM. CSDNase was found to hydrolyze DNA, and to generate 3
      phosphate and 5-OH termini. These results indicate that the nucleolytic
      properties of CSDNase are essentially the same as those of other well
      characterized acid DNases, and that CSDNase is a member of the acid DNase family.
      To our knowledge, this is the first report of an acid DNase in a fungus.

PMID- 15469736
TI  - Molecular characterization of tgd057, a novel gene from Toxoplasma gondii.
AB  - The expressed sequence tag (EST) effort in Toxoplasma gondii has generated a
      substantial amount of gene information. To exploit this valuable resource, we
      chose to study tgd057, a novel gene identified by a large number of ESTs that
      otherwise show no significant match to known sequences in the database. Northern
      analysis showed that tgd057 is transcribed in this tachyzoite. The complete cDNA
      sequence of tgd057 is 1169 bp in length. Sequence analysis revealed that tgd057
      possibly adopts two polyadenylation sites, utilizes the fourth in-frame ATG for
      translation initiation, and codes for a secretory protein. The longest open
      reading frame for the tgd057 gene was cloned and expressed as a recombinant
      protein (rd57) in Escherichia coli. Western analysis revealed that serum against
      rd57 recognized a molecule of ~21 kDa in the tachyzoite protein extract. This
      suggests that the tgd057 gene is expressed in vivo in the parasite.

PMID- 15469738
TI  - Synonymous codon usage analysis of the mycobacteriophage Bxz1 and its plating
      bacteria M. smegmatis: identification of highly and lowly expressed genes of Bxz1
      and the possible function of its tRNA species.
AB  - The extent of codon usage in the protein coding genes of the mycobacteriophage,
      Bxz1, and its plating bacteria, M. smegmatis, were determined, and it was
      observed that the codons ending with either G and / or C were predominant in both
      the organisms. Multivariate statistical analysis showed that in both organisms,
      the genes were separated along the first major explanatory axis according to
      their expression levels and their genomic GC content at the synonymous third
      positions of the codons. The second major explanatory axis differentiates the
      genes according to their genome type. A comparison of the relative synonymous
      codon usage between 20 highly- and 20 lowly expressed genes from Bxz1 identified
      21 codons, which are statistically over represented in the former group of genes.
      Further analysis found that the Bxz1- specific tRNA species could recognize 13
      out of the 21 over represented synonymous codons, which incorporated 13 amino
      acid residues preferentially into the highly expressed proteins of Bxz1. In
      contrast, seven amino acid residues were preferentially incorporated into the
      lowly expressed proteins by 10 other tRNA species of Bxz1. This analysis predicts
      for the first time that the Bxz1-specific tRNA species modulates the optimal
      expression of its proteins during development.

PMID- 15469737
TI  - Cobalt chloride-induced apoptosis and extracellular signal-regulated protein
      kinase 1/2 activation in rat C6 glioma cells.
AB  - Brain ischemia brings about hypoxic insults. Hypoxia is one of the major
      pathological factors inducing neuronal injury and central nervous system
      infection. We studied the involvement of mitogen-activated protein (MAP) kinase
      in hypoxia-induced apoptosis using cobalt chloride in C6 glioma cells. In vitro
      cytotoxicity of cobalt chloride was tested by MTT assay. Its IC(50) value was 400
      microM. The DNA fragment became evident after incubation of the cells with 300
      microM cobalt chloride for 24 h. We also evidenced nuclear cleavage with
      morphological changes of the cells undergoing apoptosis with electron microscopy.
      Next, we examined the signal pathway of cobalt chloride-induced apoptosis in C6
      cells. The activation of extracellular signal-regulated protein kinase 1/2 (ERK
      1/2) started to increase at 1 h and was activated further at 6 h after treatment
      of 400 M cobalt chloride. In addition, pretreatment of PD98059 inhibited cobalt
      chloride-induced apoptotic cell morphology in Electron Microscopy. These results
      suggest that cobalt chloride is able to induce the apoptotic activity in C6
      glioma cells, and its apoptotic mechanism may be associated with signal
      transduction via MAP kinase (ERK 1/2).

PMID- 15469739
TI  - Genetic diversity and molecular markers in introduced and Thai native apple
      snails (Pomacea and Pila).
AB  - The genetic diversity and species-diagnostic markers in the introduced apple
      snail, Pomacea canaliculata and in the native Thai apple snails; Pila ampullacea,
      P. angelica, P. pesmei, and P. polita, were investigated by restriction analysis
      of COI and are reported for the first time. Twenty-one composite haplotypes
      showing non-overlapping distributions among species were found. Genetic
      heterogeneity analysis indicated significant differences between species (P <
      0.0001) and within P. pesmei (P < 0.0001) and P. angelica (P < 0.0004). No such
      heterogeneity was observed in Pomacea canaliculata (P > 0.0036 as modified by the
      Bonferroni procedure), P. ampullacea (P = 0.0824-1.000) and P. polita (P =
      1.0000). A neighbor-joining tree based on genetic distance between pairs of
      composite haplotypes differentiated all species and indicated that P. angelica
      and P. pesmei are closely related phylogenetically. In addition, the 16S rDNA of
      these species was cloned and sequenced. A species-specific PCR for P.
      canaliculata was successfully developed with a sensitivity of detection of
      approximately 50 pg of the target DNA template. The amplification of genomic DNA
      (50 pg and 25 ng) isolated from the fertilized eggs, and juveniles (1, 7, and 15
      d after hatching) of Pomacea canaliculata was also successful, and suggested that
      Pomacea canaliculata and Pila species can be discriminated from the early stages
      of development.

PMID- 15469740
TI  - One-pot enzymatic synthesis of UDP-D-glucose from UMP and glucose-1-phosphate
      using an ATP regeneration system.
AB  - Glucose-1-phosphate uridylyltransferase from E. coli K12 was used to convert
      uridine-5'-triphosphate and glucose-1-phosphate to UDP-D-glucose. The conversion
      was efficient and completed within 5 minutes under the employed conditions. In
      addition, thymidine-5'-monophosphate kinase and acetate kinase were proven to be
      non-specific, converting udridine-5'-monophosphate to uridine-5'-triphosphate
      with 55% conversion after 6 h, which was much slower than the production of TTP
      under the same conditions (complete conversion within one hour). Since these two
      reactions could proceed under the same conditions, a one-pot synthesis of UDP-D
      glucose with ATP regeneration was designed from easily available starting
      materials, and conversion up to 40% by HPLC peak integration was achieved given a
      reaction time of 4 h.

PMID- 15469741
TI  - Gamma irradiation up-regulates expression of B cell differentiation molecule CD23
      by NF-kappaB activation.
AB  - Gamma irradiation (gamma-IR) is reported to have diverse effects on immune cell
      apoptosis, survival and differentiation. In the present study, the
      immunomodulatory effect of a low dose gamma-IR (5~10 Gy) was investigated,
      focusing on the role of NF-kappaB in the induction of the B cell differentiation
      molecule, CD23/FceRII. In the human B cell line Ramos, gamma-IR not only induced
      CD23 expression, but also augmented the IL-4-induced surface CD23 levels. While
      gamma-IR did not cause STAT6 activation in these cells, it did induce both DNA
      binding and the transcriptional activity of NF-kappaB in the IkappaB degradation
      dependent manner. It was subsequently found that different NF-kappaB regulating
      signals modulated the gamma-IR-or IL-4-induced CD23 expression. Inhibitors of NF
      kappaB activation, such as PDTC and MG132, suppressed the gamma-IR-mediated CD23
      expression. In contrast, Ras, which potentiates gamma-IR-induced NF-kappaB
      activity in these cells, further augmented the gamma-IR- or IL-4-induced CD23
      levels, The induction of NF-kappaB activation and the subsequent up-regulation of
      CD23 expression by gamma-IR were also observed in monocytic cells. These results
      suggest that gamma-IR, at specific dosages, can modulate immune cell
      differentiation through the activation of NF-kappaB, and this potentially affects
      the immune inflammatory response that is mediated by cytokines.

PMID- 15469742
TI  - [Maternal mortality: an old problem that continues in our era].

PMID- 15469743
TI  - [Binocular and monocular visors for neuroendoscopy and endoscopy-assisted
      neurosurgery].
AB  - This paper reports the testing of a lightweight wearable stereoscopic display
      during neuroendoscopies and endoscope assisted neurosurgeries. The viewers tested
      were a binocular (for the surgeon) and a monocular system (for the instrumenting
      nurse), whose optics are specially designed for wearable, portable applications
      and comprise a color corrected refractive magnifying system.

PMID- 15469744
TI  - [Cry analysis of hypoacoustic children and normal hearing children].
AB  - OBJECTIVE: We analyzed the spectrograms of the cry of deaf children and compared
      the results with those of normal children. MATERIAL AND METHODS: Twenty deaf
      children (0-2 years of age, both sexes) and 20 normal hearing children of both
      sexes within the same age range were studied. The deaf cases were selected from
      patients with high-risk pregnancies who are followed up at the National Institute
      of Perinatology (INPer), Department of Human Communication. Brainstem evoked
      potential responses were carried out in order to corroborate hearing loss in the
      affected group and to verify normal hearing in the other group. During physical
      examination in the Human Communication Clinic of the Inper, the cry was recorded
      with a Fisher tape recorder and MK2 unidirectional microphone. Sonograms were
      analyzed in the "Laboratorio de Bioacustica" of the Institute of the Human
      Communication (CNR) using the Software Cool Edit 96. We registered the
      fundamental frequency and 6 harmonic F1 at F6 (Hz). The cry frequencies of the
      deaf children were compared and of the normal hearing children using one-way
      analysis of variance. A typology of frequencies was organized by means of cluster
      analysis by the method of Ward and was compared with the study groups by means of
      contingency analysis (chi square). RESULTS: No significant difference was
      demonstrated in the fundamental frequency or in the harmonic by means of the one
      way analysis. With cluster analysis, 8 types were obtained that were not
      different when compared with the study groups. The hypothesis was rejected with
      the obtained data. CONCLUSIONS: Upon confirmation of the obtained results,
      analysis of the spectrogram of deaf children at early ages does not have the
      ability to identify the problem and thus cannot be used as a method for early
      detection of deafness.

PMID- 15469745
TI  - [Cost analysis: metronidazole-amikacin vs. preoperative monodose of ceftriaxone
      in appendicitis. Preliminary report].
AB  - INTRODUCTION: Postoperative management of acute appendicitis in our country has
      been supported by results from studies overseas. Ampicillin, clindamycin and
      gentamicin is the classic association of antimicrobial drugs. However, it is
      expensive, unnecessary and risky. We believe that a single dose can be useful.
      MATERIAL AND METHODS: We studied two groups comprised of 82 patients each in whom
      an appendectomy was performed. In group A an intravenous (i.v.) dose of
      ceftriaxone was given 30-240 minutes before skin incision. Group B or control
      group was comprised by the same number of patients previously operated and
      managed under traditional method (amikacin-metronidazole). RESULTS: In group A,
      three wound infections and an intraperitoneal abscess were identified, while in
      group B only one wound infection was seen. Average cost for patients in group A
      was 2,108.91 pesos (approx. 200 US dollars). In group B, the average cost was
      9,407.48 pesos (approx. 900 US dollars). CONCLUSIONS: One dose of preoperative
      ceftriaxone proved to be most financially economical.

PMID- 15469746
TI  - [Enterocutaneous fistulas in patients older than 70 years].
AB  - INTRODUCTION: Enterocutaneous fistula remains a major complication after
      abdominal surgery. MATERIAL AND METHODS: We reviewed the charts of patients over
      70 years of age with enterocutaneous fistula who were seen in a general surgery
      department. Special interest was given to mortality-related factors. RESULTS: A
      total of 19 patients were seen. The median age was 76 years. All fistulas were
      postoperative. All patients were managed based on the phases of Chapman and
      Sheldon. The most common site of presentation was colon, followed by jejunum and
      duodenal fistulas. More than half of the patients were malnourished at time of
      presentation. Spontaneous closure presented in eight patients (47%), seven other
      patients required surgical treatment for closure of their fistulas. Closure of
      the fistulas was obtained in 15 patients (79%). Four patients died resulting in a
      mortality rate of 21%. The factors against spontaneous closure were high output
      (p < 0.03), jejunal fistulas (p < 0.05), hydroelectrolytic imbalance (p < 0.01)
      and multiple fistulas (p < 0.02). The factors related to mortality were high
      output (p < 0.04), hydroelectrolytic imbalance (p < 0.02), jejunal fistulas (p <
      0.04) and sepsis (p < 0.01). CONCLUSION: Patients > 70 years of age with
      enterocutaneous fistulas have the same mortality reported in the overall
      population. Sepsis remains the most important cause of death in patients with
      enterocutaneous fistulas.

PMID- 15469747
TI  - [Thromboprophylaxis in post-surgical patients: review of 1,500 cases].
AB  - Deep venous thrombosis (DVT) and pulmonary embolism (PE) are entities with a
      relative high frequency in post-surgical patients and can occur immediately after
      the surgical procedure or even two or three weeks after the surgical event. In
      the United States and Europe, DVT is present in over 5 million events each year,
      while PE is present in over 500,000 cases. The purpose of this study is to review
      the cases that undergo surgery during a period of three months (1,500 cases),
      from June 15th to September 15th, 2003, at the Angeles of Pedregal Hospital in
      Mexico City, in order to evaluate the type of risk that each one represents
      (International Consensus, 1997 ACCP, and the 2000 Mexican Consensus over venous
      thromboembolism (VTE) questionnaire), and the prophylaxis applied in each case,
      to be compared with international standards. The Angeles of Pedregal Hospital
      maintains a general prophylactic standard with its patients equivalent in number
      to the international standard; however, there is deficiency in the measures taken
      in orthopedic, high-risk, and very high-risk patients, where prophylaxis was low.
      It has also been called to our attention that the prophylactic measures taken
      were insufficient, both in the type of measure that was chosen and the
      combination of those that were applied, which in relation to the international
      recommendations were extremely low.

PMID- 15469748
TI  - [Maternal mortality at the Mexican Institute of Social Security (IMSS). Initial
      results from a reduction intervention strategy].
AB  - OBJECTIVE: To analyze the preliminary results of a medical manager intervention
      to improve the quality of medical care during pregnancy, delivery and puerperium,
      on the maternal mortality rates in population covered by the Mexican Institute of
      Social Security (IMSS). MATERIAL AND METHODS: We selected the 14 administrative
      delegations of IMSS that showed the highest rates and absolute numbers of
      maternal deaths in the years 1999 to 2001. Within this group, the manager medical
      staff developed activities for medical training of family physicians and
      gynecologists, to improve medical resources, to achieve a better coordination
      among medical services, to adequate reference of obstetrical complications to
      higher-level hospitals, and for monitoring of maternal mortality committees
      operation. The other 23 IMSS administrative delegations were used as controls.
      RESULTS: Maternal mortality rates fell down from 40.7 to 28.2 per 100,000 live
      births among the delegations included in the strategy (mean reduction 30.7%).
      Among the control delegations maternal mortality rate fell down 1.5% only (32.3
      to 31.8 per 100,000 live births). A similar phenomenon was observed for the
      absolute number of maternal deaths, with a reduction of 36.7% and 8.4%,
      respectively. CONCLUSIONS: The improving intervention was associated with a
      noticeable reduction in the maternal mortality rate. It is necessary a long-term
      observation to confirm a cause-effect relationship.

PMID- 15469749
TI  - [Antihyperalgesic activity of chlorimipramine and sodium phenytoin in an induced
      model of neuropathic pain in rats].
AB  - INTRODUCTION: Neuropathic pain results from injury or impairment of the nervous
      system manifested by pain syndrome. Experimental models have been used to study
      its effects and how to suppress these. Tricyclic antidepressants (TCA) and
      anticonvulsant (AC) have been used for treatment. OBJECTIVE: To evaluate the
      antihyperanalgesic efficiency of intraperitoneal (IP) chlorimipramine (CIP) vs IP
      phenytoine (DFH) for induced neuropathic pain in an experimental animal model.
      METHODS: After making a surgical ligature of the sciatic nerve in the right leg
      of 18 male rats, the time of withdrawal of both claws immersed in hot (45 degrees
      C) and cold water (10 degrees C) was measured during a four week period before
      and after IP CIP, DFH, or placebo administered in a double blind study. RESULTS:
      Significant statistical differences were observed in the time of withdrawal with
      CIP as compared with DFH and when both groups were compared with placebo (as
      tested by the paw immersion in hot water). When the thermal stimulus was cold
      water, an increase of the time of withdrawal was seen with DFH. CONCLUSIONS:
      These findings suggest that CIP and FS are both effective in the treatment of
      neuropathic pain in an animal model, as well as for the treatment of secondary
      hiperalgesia.

PMID- 15469751
TI  - [Communication and auditory behavior obtained by auditory evoked potentials in
      mammals, birds, amphibians, and reptiles].
AB  - METHODS:  ANIMALS: amphibians, Frog catesbiana (frog bull, 30 animals); reptiles,
      Sceloporus torcuatus (common small lizard, 22 animals); birds: Columba livia
      (common dove, 20 animals), and mammals, Cavia porcellus, (guinea pig, 20
      animals). With regard to lodging, all animals were maintained at the Institute of
      Human Communication Disorders, were fed with special food for each species, and
      had water available ad libitum. Regarding procedure, for carrying out analysis of
      auditory evoked potentials of brain stem SPL amphibians, birds, and mammals were
      anesthetized with ketamine 20, 25, and 50 mg/kg, by injection. Reptiles were
      anesthetized by freezing (6 degrees C). Study subjects had needle electrodes
      placed in an imaginary line on the half sagittal line between both ears and eyes,
      behind right ear, and behind left ear. Stimulation was carried out inside a no
      noise site by means of a horn in free field. The sign was filtered at between 100
      and 3,000 Hz and analyzed in a computer for provoked potentials (Racia APE 78).
      RESULTS: In data shown by amphibians, wave-evoked responses showed greater
      latency than those of the other species. In reptiles, latency was observed as
      reduced in comparison with amphibians. In the case of birds, lesser latency
      values were observed, while in the case of guinea pigs latencies were greater
      than those of doves but they were stimulated by 10 dB, which demonstrated best
      auditory threshold in the four studied species. Last, it was corroborated that as
      the auditory threshold of each species it descends conforms to it advances in the
      phylogenetic scale. CONCLUSIONS: Beginning with these registrations, we care able
      to say that response for evoked brain stem potential showed to be more complex
      and lesser values of absolute latency as we advance along the phylogenetic scale;
      thus, the opposing auditory threshold is better agreement with regard to the
      phylogenetic scale among studied species. These data indicated to us that seeking
      of auditory information is more complex in more evolved species.

PMID- 15469752
TI  - [Bouveret's syndrome. Case report].
AB  - INTRODUCTION: Bouveret's syndrome is characterized by piloro-duodenal obstruction
      following the implant of a giant gallstone with gallstone ileus origin. It
      constitutes the less common variety of gallstone ileus (1-3%), mainly affecting
      elderly patients with chronic degenerative illnesses, possibly with high
      mortality. OBJECTIVE: We report the case of a patient with a less common variety
      of gallstone ileus. The patient was treated at a third-level care hospital.
      CLINIC CASE: Patient is a 52-year-old male with gastric obstruction and secondary
      dehydration. Studies were supported by a series of esophagus-gastric-duodenal and
      broad endoscopy. Piloro-duodenal obstruction by a giant gallstone was reported
      which could not be extracted by endoscopy. The patient was taken to surgery where
      a giant gallstone lying in the duodenal site was found and biliary vesicular
      scleroatrophic. Gastrotomy is effected with the extraction of the gallstone and
      gastrography. Gallstone duodenal fistula is then identified with support
      analysis. CONCLUSIONS: Bouveret's syndrome is a rare entity whose diagnosis has a
      high sensitivity and specificity with a supported radiographic diagnosis.
      Endoscopy is difficult in the case of a giant impacted gallstone, making surgery
      the best therapeutic choice.

PMID- 15469753
TI  - [Thrombosed cavernous hemangioma of the anterior mediastinum. A report of one
      case].
AB  - Mediastinum hemangioma is a rare benign tumor. We performed surgery and present
      the first reported case in Chile. The patient is a 24-year-old symptomatic woman,
      referred to our hospital from a rural health center. The patient had all routine
      preoperative studies, chest radiographs and computed tomography of the thorax. We
      performed a median sternotomy with a complete resection of the mass. During the
      36-month follow-up, she was well, asymptomatic and without relapse evidence. A
      review of the most outstanding characteristics of this rare tumor is presented.

PMID- 15469754
TI  - [Acute intestinal obstruction provoked by intraperitoneal secretion of ovarian
      tumor. A clinical case].
AB  - We report here of the case of a 53-year-old woman who presented with intestinal
      obstruction without response to medical treatment. Exploratory laparotomy
      produced a moderate quantity of yellowish-green liquid and agglutination of semi
      dough-like material. Separation of the flaps of intestine and colon was easily
      done by the fingers. A grayish white mass of 10 x 15 cm was seen in the left
      annex, with a perforation which released the semi-dough-like material. Wide
      resection of the corresponding annex was carried out. Anatomopathologic
      examination revealed malignant thecoma with resected free borders of at least 2
      cm which was moderately differentiated. Because endometrial biopsy was normal, we
      decided against further hysterectomy. The patient was referred to an oncologist
      who did not recommend chemotherapy. The patient was reviewed one year later and
      was found to be free of tumor and in good condition although with some evidence
      of occlusive blocking. There have been only four similar cases in the literature
      in which intestinal obstruction by the same mechanism appeared, also indicating
      that the finding of malignant thecoma is rare.

PMID- 15469755
TI  - [Acute myeloblastic leukemia (M5) and aspergilloma in a 75-year-old man].
AB  - We report here a case of pulmonary aspergilloma in a patient with acute
      myeloblastic leukemia. We present the clinical and radiological characteristics
      of this case. Aspergillus flavus was isolated. The antifungal treatment was
      unsuccessful. Pulmonary aspergillomas are associated with a high mortality in the
      immunocompromised host. It is important to know the diagnostic approach and the
      surgical and medical treatment of this disease.

PMID- 15469756
TI  - [Pseudothrombocytopenia induced by ethylenediaminetetraacetic acid in burned
      patients].
AB  - The EDTA-dependent pseudothrombocytopenia is a false decrease in the number of
      platelets below the normal value when analyzed with automated devices. There is
      an incidence of 0.09 to 0.21% in hospitalized patients. Pseudothrombocytopenia is
      secondary to platelet clumping induced by antibodies in the presence of EDTA and
      has been associated with sepsis, cancer, cardiac surgery and drugs. We report the
      first case of pseudothrombocytopenia induced by EDTA in a burn patient.

PMID- 15469757
TI  - [Inaugural speech of the Seventy-First Academic Year of the Mexican Academy of
      Surgery].

PMID- 15469759
TI  - [Detection of thyroid disease during surgical exploration of the neck for primary
      hyperparathyroidism].

PMID- 15469760
TI  - [Detection of thyroid disease during surgical exploration of the neck for primary
      hyperparathyroidism].

PMID- 15469761
TI  - Contemporary management of chronic pain disorders.

PMID- 15469762
TI  - Opioids in chronic pain management: Navigating the clinical and regulatory
      challenges.

PMID- 15469763
TI  - Approach to assessment and diagnosis of chronic pain.

PMID- 15469764
TI  - Politics and family medicine: vote November 2.

PMID- 15469770
TI  - How the presidential candidates' health care proposals contrast.

PMID- 15469771
TI  - Facial lesion that came "out of nowhere".

PMID- 15469772
TI  - Practice pearls.

PMID- 15469773
TI  - Ottawa Ankle Rules accurately asses injuries and reduce reliance on radiographs.

PMID- 15469774
TI  - Raloxifene reduces risk of vertebral fractures [corrected] in postmenopausal
      women regardless of prior hormone therapy.
AB  - OBJECTIVE: We examined whether past use of hormone therapy influences the effects
      of raloxifene on the risk of new vertebral fracture, cardiovascular events, or
      breast cancer. STUDY DESIGN: The Multiple Outcomes of Raloxifene Evaluation
      (MORE) trial examined vertebral fracture incidence as the primary endpoint,
      breast cancer incidence as a secondary endpoint. Cardiovascular events were
      collected as secondary safety endpoints. POPULATION: The MORE trial enrolled 7705
      postmenopausal women. Of the 7682 women who reported their previous HT use
      status, 29% used HT before screening. OUTCOMES MEASURED: Separate logistic
      regression models analyzed the relationships between prior HT use and the risk of
      vertebral fracture, cardiovascular events, or breast cancer. Interaction terms
      with P<.10 were considered to be statistically significant. Confidence intervals
      for relative risks (RR) were calculated using the Mantel-Haenszel method.
      RESULTS: Raloxifene 60 mg/d, the clinically approved dose for osteoporosis
      prevention and treatment, reduced the risk of vertebral fractures by 54%
      (RR=0.46) and 29% (RR=0.71) in women with and without prior HT use, respectively
      (interaction P=.05). A lower incidence of invasive breast cancer in women with
      prior HT use (RR=0.23) and in women without prior HT use [RR=0.31; interaction
      P=.60] was observed in women receiving raloxifene (pooled doses). Irrespective of
      prior HT use, women treated with raloxifene (pooled doses) had no change in
      incidence of cardiovascular events (interaction P=.56). CONCLUSIONS: The risk of
      vertebral fractures was lower in women treated with raloxifene, regardless of
      prior HT use, but there was a suggestion that the effect was greater in women who
      had used HT. Women randomized to receive raloxifene exhibited a decreased
      incidence of invasive breast cancer, compared with women receiving placebo. No
      change occurred in the incidence of cardiovascular events, regardless of prior HT
      use.

PMID- 15469775
TI  - How should we manage Bell's palsy?

PMID- 15469776
TI  - A new treatment option for grade II and IV hemorrhoids.

PMID- 15469777
TI  - Abnormal vaginal discharge: using office diagnostic testing more effectively.

PMID- 15469778
TI  - Optimizing combination therapy for type 2 diabetes in adolescents and adults: a
      case-based approach.
AB  - Children and adolescents who are overweight and have additional risk factors (ie,
      high-risk ethnic group or signs of insulin resistance) should be screened for
      diabetes every 2 years (strength of recommendation [SOR]: C). Management of type
      2 diabetes in all age groups requires a multifactorial approach that addresses
      not only glycemic control (A1C <7%) but also other cardiovascular risk factors
      such as hypertension, dyslipidemia, and obesity (SOR: A). Most patients with type
      2 diabetes will eventually require combination therapy with 2 or more agents to
      attain and maintain glycemic control (SOR: A). Combining an insulin secretagogue
      (ie, sulfonylurea or meglitinide) and an insulin sensitizer (ie, metformin or a
      glitazone) capitalizes on unique mechanisms of action and results in significant
      A1C lowering (SOR: C). If a patient is unable to achieve glycemic control on 2
      oral agents, insulin therapy is an appropriate consideration and should be added
      to oral agents (rather than substituted) (SOR: B).

PMID- 15469779
TI  - Clinical inquiries. How should we treat chronic daily headache when conservative
      measures fail?

PMID- 15469780
TI  - Clinical inquiries. Should we screen for bacterial vaginosis in asymptomatic
      patients at risk for preterm labor?

PMID- 15469781
TI  - Clinical inquiries. How reliable are self-measured blood pressures taken at home?

PMID- 15469782
TI  - Clinical inquiries. What effect do inhaled steroids have on delaying the
      progression of COPD?

PMID- 15469783
TI  - Clinical inquiries. How effective is prophylactic therapy for gout in people with
      prior attacks?

PMID- 15469784
TI  - Clinical inquiries. Does tight control of blood glucose in pregnant women with
      diabetes improve neonatal outcomes?

PMID- 15469786
TI  - [The Manresa study: a stimulus to the development of cardiovascular epidemiology
      in Spain].

PMID- 15469785
TI  - [Endothelial dysfunction, inflammation and statins: new evidences].

PMID- 15469787
TI  - [Noninvasive assessment of the effect of atorvastatin on coronary
      microvasculature and endothelial function in patients with dyslipidemia].
AB  - INTRODUCTION AND OBJECTIVES: The effect of statins has been monitored mainly in
      peripheral arteries. It is now possible to study coronary microcirculation by
      analyzing coronary reserve with transthoracic echocardiography. The aim of this
      study was to use this noninvasive technique to evaluate the effect of
      atorvastatin on peripheral endothelial function and on the coronary
      microvasculature in patients with dyslipidemia. PATIENTS AND METHOD: We included
      21 patients with dyslipidemia but no clinical antecedents of atherosclerosis.
      Mean (SD) age was 64.9 (11) years, and women made up 61.9% of the group. All
      patients were treated with 20 mg atorvastatin during 3 months. Lipid profile,
      carotid intima-media thickness, endothelium-dependent vasodilation and coronary
      flow reserve were determined at baseline and at the end of treatment. All studies
      were performed with echocardiographic techniques. RESULTS: Together with
      improvements in the lipid profile, we found a 43% increase in endothelium
      dependent vasodilation (4.3 [4.4] to 6.2 [3.8]; P=.07) and a 25% increase in
      coronary flow reserve (2.5 [0.6] vs 3.1 [0.8]; P=.002). The increase in
      endothelium-dependent vasodilatation correlated with age (r=-0.60; P=.004),
      intima-media thickness (r=-0.47; P=.029), low-density lipoprotein level before
      treatment (r=-0.43; P=.05), and baseline endothelium-dependent vasodilatation (r=
      0.63; P=.002). The increase in coronary flow reserve correlated with low-density
      lipoprotein level after treatment (r=-0.51; P=.04). CONCLUSIONS: Short-term
      treatment with atorvastatin improved the lipid profile, coronary microvascular
      function and endothelium-dependent vasodilation in the peripheral circulation.
      The noninvasive assessment of coronary reserve is feasible with transthoracic
      echocardiography.

PMID- 15469788
TI  - [Effect of the early administration of pravastatin on C-reactive protein and
      interleukin-6 levels in the acute phase of myocardial infarction with ST segment
      elevation].
AB  - INTRODUCTION AND OBJECTIVES: C-reactive protein (CRP), whose synthesis in the
      liver is regulated by interleukin 6 (IL-6), is related with the prognosis for
      ischemic heart disease. The aim of this study was to evaluate the effect of early
      administration of pravastatin on plasma levels of CRP and IL-6 in patients with
      acute myocardial infarction and ST segment elevation. PATIENTS AND METHOD: 71
      patients were randomized during the first 10 hours from the onset of symptoms to
      receive 40 mg of pravastatin once a day or not. CRP and IL-6 were measured on
      admission, 48 hours and 7 days later. CRP was also measured 2 months later.
      RESULTS: On admission, levels of CRP and IL-6 were similar in both groups. After
      7 days of treatment the administration of pravastatin was associated with a lower
      level of CRP (P=.002). Mean and median CRP levels decreased from 48 hours to day
      7 by 48.4% and 51.9% respectively in the pravastatin group, and by 32.5% and
      15.9% respectively in the control group. In contrast, no significant differences
      in IL-6 levels were observed between the two groups. After 2 months of follow-up,
      50% of the treated patients and 25% of the control patients had CRP levels lower
      than 6.6 mg/L (P=.039). CONCLUSIONS: Early administration of pravastatin in the
      acute phase of myocardial infarction with ST segment elevation was associated
      with a lower level of CRP after 7 days of treatment, with no concomitant changes
      in IL-6 levels.

PMID- 15469789
TI  - [Patterns of mortality in a cohort of workers followed during 28 years: the
      Manresa study].
AB  - INTRODUCTION AND OBJECTIVES: To describe mortality patterns in a cohort of
      workers followed for 28 years, to estimate possible trends, and to compare the
      findings with those for the general population. SUBJECTS AND METHOD: The cohort
      included 1059 healthy male workers aged 30 to 59 years and followed for 28 years.
      Physical examinations and structured interviews were carried out every 5 years.
      Deaths were recorded from death certificates. The standardized mortality ratio
      (SMR) was calculated using sex- and age-specific mortality rates for the Catalan
      population as a reference for the same time period. RESULTS: The number of
      observed deaths in this cohort was 259 (24%). The main causes of death were
      cardiovascular diseases (n = 90, 35%) and cancer (n = 90, 35%). No excess
      mortality was observed in the cohort in comparison to the general population. All
      cause mortality was lower, and cause-specific mortality was lower than or similar
      to rates in the general population. Overall, 382 deaths were expected, resulting
      in a significantly lower standardized mortality ratio of 67.7% (95% CI: 59.7%
      76.5%). CONCLUSIONS: The patterns of mortality in this cohort of male workers
      were similar to those in the general population. Total mortality was lower than
      expected--evidence of the "healthy worker effect" which was particularly strong
      during the early part of the follow-up period.

PMID- 15469790
TI  - [Reproducibility of measurements of left ventricular function with gated
      myocardial perfusion SPECT and comparison with blood pool radionuclide
      ventriculography].
AB  - INTRODUCTION AND OBJECTIVE: This study was designed to evaluate the
      reproducibility of ejection fraction (EF) and ventricular volume measurements
      obtained with single photon emission computed tomography (gated-SPECT), and to
      assess the correlation between EF values obtained with this method and blood pool
      planar radionuclide ventriculography. PATIENTS AND METHOD: A total of 55 patients
      were included (37 men, mean age 61.3 years) upon referral to two nuclear
      cardiology units for diagnosis (50%) or follow-up of known coronary artery
      disease. In a standard 2-day protocol, patients received a dose of
      [99mTc]tetrofosmin (800 MBq) at stress and at rest. Two resting gated-SPECT
      studies were performed. QGS software was used to obtain left ventricular EF, end
      diastolic volume (EDV) and end-systolic volume (ESV). Forty-nine patients agreed
      to undergo blood pool ventriculography on the third day. RESULTS: Interobserver
      variability was 0.5 (2.6)% (r=0.99) for EF, 1.9 (10.7) mL for EDV (r=0.98) and
      0.5 (5.4) mL for ESV (r=0.99). Interassay variability was 2 (5.1)% (r=0.94) for
      EF, 4.5 (8.6) mL for EDV (r=0.99) and 3.4 (6.6) mL for ESV (r=0.99). The
      correlation between gated-SPECT EF and blood pool EF was suboptimal (r=0.75,
      95%CI, 0.59-0.85). CONCLUSIONS: There was excellent interobserver and interassay
      reproducibility for left ventricular functional parameters measured with gated
      SPECT and QGS software, and this method can be used for serial evaluations of
      ventricular function. Although the correlation between values obtained with gated
      SPECT and blood pool ventriculography was acceptable, the differences show that
      the two techniques cannot be considered equivalent.

PMID- 15469791
TI  - [Ablation of permanent atrial fibrillation in cardiac surgery. Short-term and mid
      term results].
AB  - INTRODUCTION: Surgical ablation of atrial fibrillation is currently a simple
      procedure that can be done during cardiac surgery in most patients. A number of
      different energy sources now available allow to easily create ablation lines in
      the atria. We describe our experience during the previous three years. PATIENTS
      AND METHOD: In 93 patients with cardiac problems treated with surgery and
      permanent atrial fibrillation (longer than 3 months), surgical ablation of the
      arrhythmia was done at the same time. Mean duration of the atrial fibrillation
      was 6 years (range 0.3 to 24 years). Mean (SD) preoperative size of the atrium as
      measured echocardiographically was 51.7 (8.8) mm (range 35 to 77 mm). RESULTS:
      Five patients died in the hospital (5.3% in-hospital mortality). After a mean
      follow-up of 10 months, 83.8% of the patients had recovered and maintained sinus
      rhythm, and 16.1% of the patients remained in atrial fibrillation. A permanent
      pacemaker was implanted in 3 of these patients. Among the 82 patients followed
      for more than 6 months, the prevalence of sinus rhythm was 84.1%.
      Echocardiographically documented contractility in both atria was observed in 50%
      of the patients. Major complications related to the ablation procedure occurred
      in 3.5% of the patients, and consisted of a perivalvular leak 2 months after
      surgery, a circumflex artery spasm, and an atrio-esophageal fistula. CONCLUSIONS:
      Surgical ablation of permanent atrial fibrillation is a simple procedure
      associated with low morbidity and mortality, and with recovery of sinus rhythm in
      most patients. The main problem with the procedure is the incidence of early
      postoperative arrhythmias.

PMID- 15469792
TI  - [Efficacy of oral sildenafil as rescue therapy in patients with severe pulmonary
      arterial hypertension chronically treated with prostacyclin. Long-term results].
AB  - INTRODUCTION AND OBJECTIVE: Prostacyclin therapy is an effective treatment for
      severe pulmonary hypertension. Sildenafil, a selective phosphodiesterase type 5
      inhibitor, induces selective vasodilatation of the pulmonary vessels. A
      synergistic effect has been described for these two drugs. The aim of this study
      was to evaluate the efficacy and safety of sildenafil as rescue therapy in
      patients with severe pulmonary hypertension on chronic treatment with
      prostacyclin whose clinical or functional course was unsatisfactory. PATIENTS AND
      METHOD: Observational study of 11 patients (7 men, 4 women, mean age 42 [8]
      years) diagnosed as having severe idiopathic pulmonary hypertension, who were
      receiving chronic prostacyclin therapy. Sildenafil was started after a worsening
      of their clinical or functional status. Baseline, 3-month and 12-month follow-up
      evaluations were based on functional status (NYHA functional class and 6-minute
      walking test), the presence of decompensated right heart failure and
      echocardiogram. RESULTS: Seven of the 11 patients showed significant improvements
      in exercise capacity (distance walked in 6 minutes) at 3 (+25 m) and 12 months'
      follow-up (+36 m). Improvements in functional class were seen, and heart failure
      disappeared. No significant adverse effects of sildenafil were detected. The
      echocardiographic parameters showed a significant reduction in right ventricular
      end-diastolic diameter and left ventricular diastolic eccentricity index. One
      patient died after 4 months of follow-up from sudden cardiac death. CONCLUSIONS:
      The addition of oral sildenafil to chronic prostacyclin treatment in patients
      with severe pulmonary hypertension improved functional capacity and reduced
      episodes of decompensated right heart failure, with good tolerance and no
      significant adverse effects.

PMID- 15469793
TI  - [Guidelines on prevention, diagnosis and treatment of infective endocarditis.
      Executive summary].

PMID- 15469794
TI  - [Expert consensus document on the use of antiplatelet agents].

PMID- 15469795
TI  - [Future perspectives in the treatment of heart failure: from cell transplantation
      to cardiac regeneration].
AB  - The last few years have witnessed growing interest in regenerative therapy for
      the failing heart by cell transplantation. Although initial studies with skeletal
      myoblasts are more than 10 years old, the potential of bone marrow-derived cells
      has led to a flurry of experimental studies generating generally positive but
      occasionally contradictory results. This has given rise on not a few occasions to
      conflicting viewpoints regarding the ethics of initiating clinical trials. We
      feel it is appropriate to offer a critical view of the use of stem cells for
      heart failure. Perhaps the thorniest question to answer at this time is whether
      clinical trials are justified or not in the light of current knowledge, or
      whether we should acquire deeper knowledge of the possible efficacy and safety of
      this type of treatment, and of the mechanisms that account for its efficacy,
      before we so much as initiate studies in humans. We feel there is now sufficient
      evidence to justify the performance of clinical trials despite the undoubtedly
      numerous questions that remain to be answered with experimental studies in
      animals.

PMID- 15469796
TI  - [Right atrial thrombus related to venous catheter].

PMID- 15469797
TI  - [Cardiac perforation complicated by cardiac tamponade and sealed with metallic
      coils].
AB  - Distal coronary artery perforation with an angioplasty guidewire is a rare
      complication that may cause cardiac tamponade, myocardial infarction, arrhythmia,
      and even death. The use of platelet IIb/IIIa glycoprotein receptor inhibitors
      increases the risk of potentially fatal complications that are difficult to
      manage. We report a patient on treatment with abciximab who presented coronary
      perforation in a distal branch of the right coronary artery caused by the
      coronary guidewire tip, and complicated by acute cardiac tamponade. Blood
      extravasation to the pericardium was stopped by releasing two metallic coils into
      the distal vessel, thereby avoiding the need for emergent cardiac surgery.

PMID- 15469798
TI  - [Tricuspid valve endocarditis in a nonaddicted patient without predisposing
      myocardiopathy].
AB  - Right-sided endocarditis is exceptional in non-drug addict patients without
      previous heart disease. Few cases have been published, and its diagnosis
      sometimes presents a significant clinical challenge. We describe a 57-year-old
      patient with no history of parenteral drug addiction or vascular catheter use,
      who had tricuspid valve endocarditis in a morphologically normal valve. The
      clinical debut was characterized by acute febrile syndrome, purpura (petechia) on
      the legs, and oligoarthritis. This entity usually has a good prognosis and
      responds well to treatment, and presents certain common clinical features
      (persistent fever, pulmonary lesions, anemia and microscopic hematuria) that can
      lead the clinician to suspect the diagnosis. However, diagnosis should be based
      on microbiological studies (S. aureus is the organism isolated most often) and on
      echocardiographic findings.

PMID- 15469799
TI  - [Recurrent coronary thrombosis, factor V Leiden, primary antiphospholipid
      syndrome and HIV].
AB  - We describe a 54-year-old man who was HIV-positive, admitted for cardiogenic
      shock complications inferior myocardial infarction. He was treated with primary
      percutaneous transluminal angioplasty (PCTA) and stent deployment in mid right
      coronary artery. After a few days thrombotic occlusion of the stent occurred, and
      the problem recurred during implantation of a new stent in the course of a second
      PTCA. We detected coinheritance of factor V Leiden, primary antiphospholipid
      syndrome and antithrombin deficiency. We discuss the role of these coagulation
      disorders in acute myocardial infarction as well as the treatment and course of
      the coronary syndrome in this context.

PMID- 15469802
TI  - [National and international impact factor of Anales de Pediatria].
AB  - INTRODUCTION: The aim of this study was to present bibliometric indicators of the
      impact of Anales de Pediatria in 2001 and to compare this journal with other
      Spanish pediatrics journals. MATERIAL AND METHOD: A total of 5,388 bibliographic
      references from 1999, 2000 and 2001 corresponding to citable articles published
      in 2001 in a sample of 87 selected Spanish medical journals were analyzed. The
      indicators obtained were the number of citations, the national and international
      impact factor (IF) and the immediacy index. RESULTS: The national IF of Anales de
      Pediatria was 0.334 and the international IF was 0.372. The immediacy index was
      0.111. DISCUSSION: This study confirms the leadership of Anales de Pediatria,
      since this journal is the most frequently cited Spanish pediatrics journal and
      has the highest IF and immediacy index. The bibliometric indicators obtained are
      comparable with those observed in other journals included in Journal Citation
      Reports.

PMID- 15469803
TI  - [Comparative efficacy of oral deflazacort versus oral prednisolone in children
      with moderate acute asthma].
AB  - OBJECTIVES: To assess the efficacy and tolerability of oral deflazacort versus
      oral prednisolone in acute moderate asthma in children. PATIENTS AND METHODS: We
      performed a prospective, randomized, parallel group trial of children aged 6 to
      14 years old with a diagnosis of asthma who presented to the pediatric emergency
      department for moderate asthma exacerbation. All patients were administered short
      acting beta2-adrenergic agonists. The intervention groups received either oral
      deflazacort (1.5 mg/kg) or prednisolone (1 mg/kg) for 7 days. The primary outcome
      measure was forced expiratory volume in 1 second (FEV1) and secondary outcome
      measures were pulmonary symptom score index, peak expiratory flow rate (PEFR),
      hospitalization rate and the use of rescue beta2-agonists. Patients were
      evaluated at the start of treatment (visit 1), on day 2 (visit 2) and on day 7
      (visit 3). RESULTS: Of the 54 children enrolled, two were hospitalized on visit 2
      (one from each group). Baseline clinical data were similar in both groups: FEV1:
      53 and 51 %; bronchodilator test: 119 and 121 %; PEFR: 169 and 165 L/min; symptom
      score: 6 and 6.5 for the deflazacort and prednisolone groups, respectively. On
      visit 2, all measures improved: FEV1: 122.2 and 126.5 % (p < 0.05); PEFR: 164 and
      149 L/min (p < 0.05); symptom score: -4.4 and -3.8 (p < 0.05), without
      significant differences between groups. On visit 3 all variables continued to
      show improvement: FEV1: 133.2 and 132.5 % (p < 0.05); PEFR: 1115.7 and 187.6
      L/min (p < 0.05); symptom score: -5.4 and -5.9 (p < 0.05), without significant
      differences between groups. No adverse effects were reported. CONCLUSIONS:
      Deflazacort and prednisolone show similar efficacy in improving pulmonary
      function and in producing clinical improvement in the management of acute
      moderate asthma in children.

PMID- 15469804
TI  - [Respiratory infections due to metapneumovirus in hospitalized infants].
AB  - BACKGROUND: Human metapneumovirus (hPMV) is a recently identified virus that is
      recognized as a cause of respiratory tract illness in the pediatric population.
      OBJECTIVES: To determine the incidence of respiratory tract infections caused by
      hPMV in hospitalized infants and to describe the clinical characteristics and
      possible presence of coinfection with other viral agents. PATIENTS AND METHODS:
      We performed a prospective study from September to June 2003 in all children aged
      less than 24 months who were admitted to the Severo Ochoa Hospital (Leganes,
      Madrid) with a respiratory tract infection. Virological diagnosis was made with a
      direct immunofluorescent assay and/or reverse transcriptase-polymerase chain
      reaction on specimens obtained from nasopharyngeal washing. Demographic and
      clinical data from patients with an hPMV respiratory tract infection were
      analyzed. RESULTS: During the study period, 200 infants were admitted with a
      respiratory tract infection, of which 18 (9 %) had an hPMV infection. HPMV was
      the viral agent isolated in 13.8 % of positive nasopharyngeal washings. All
      patients were admitted between March and April. The mean age was 6.7 +/- 6.1
      months. The most common diagnoses were recurrent wheezing (55.5 %) and
      bronchiolitis (38.8 %). Oxygen therapy was required by 55.5 % of infants during
      hospitalization. Coinfection with other respiratory viruses was confirmed in 33.3
      % of the patients. CONCLUSIONS: Human metapneumovirus is a major cause of
      respiratory tract illness in hospitalized infants. This virus causes mainly
      bronchiolitis and recurrent wheezing and is more frequent in spring. Coinfection
      with other respiratory viruses is frequent.

PMID- 15469805
TI  - [Chest radiograph in bronchiolitis: is it always necessary?].
AB  - BACKGROUND: The routine use of chest radiograph in infants with bronchiolitis
      increases health costs and can often unnecessarily expose the patient to
      radiation. OBJECTIVES: To evaluate the prevalence of infiltrate/atelectasis in
      infants younger than 2 years who presented to the emergency department with
      bronchiolitis, to assess whether patient management is changed after viewing the
      chest radiograph and to determine which clinical variables can accurately
      identify children with normal radiographs, with a view to reducing unnecessary
      radiological investigations. PATIENTS AND METHODS: From October 2003 to December
      2004, infants aged < 24 months evaluated in the emergency department of the
      Severo Ochoa Hospital (Madrid) with a diagnosis of bronchiolitis were included in
      this study. The variables registered were age, sex, time since onset, respiratory
      rate, temperature, asymmetry on auscultation, oxygen saturation and the virus
      identified. A chest radiograph was obtained and the need for admission was
      evaluated before and after obtaining the results. RESULTS: Two hundred fifty-two
      infants were included, of which 50 % were aged less than 5 months.
      Infiltrate/atelectasis was identified in 14.3 % (95 % CI: 10.1-18.5; kappa
      coefficient: 0.64). Patients with infiltrate/atelectasis were 2.5 times more
      likely to have a temperature of > or = 38 degrees C (p: 0.004), O2 saturation of
      < 94 % (p: 0,006) and to be admitted before the results of chest radiograph were
      known. No differences were found between children with and without infiltrate in
      age at presentation, sex, disease duration, respiratory rate or identified virus.
      Patient management was modified in 30 % of patients with infiltrate/ atelectasis.
      Patients with a temperature of < 38 degrees and O2 saturation of > 94 % had a 92
      % probability of normal chest radiograph. CONCLUSIONS: Most infants presenting
      with bronchiolitis had a normal chest radiograph. Temperature >or = 38 degrees
      and O2 saturation < 94 % were significantly associated with
      infiltrate/atelectasis. In most infants with bronchiolitis, the absence of fever
      and hypoxia are good predictors of normal chest radiographs.

PMID- 15469806
TI  - [Reduction in infant mortality in Chile between 1990 and 2001].
AB  - OBJECTIVES: To present the change in infant mortality (IM) in Chile and its
      possible explanations. METHODS: We performed a time-series study. Data on infant
      mortality were gathered from the demographic yearbooks of the National Institute
      of Statistics and from the health programs implemented by the Ministry of Health.
      RESULTS: The IM rate fell from 16 per 1000 live newborns in 1990 to 8.3 per 1000
      in 2001. Programs for the use of surfactant and for the surgical management of
      cardiac malformations in newborns were implemented. Programs for the early
      treatment of acute respiratory infection were also implemented and new vaccines
      were introduced into the National Immunization Program in infants. CONCLUSIONS:
      The fall in infant mortality in Chile between 1990 and 2001 may be partly due to
      the implementation of the above-mentioned programs.

PMID- 15469807
TI  - [Information and quality of care in a pediatric intensive care unit. Parents'
      opinion].
AB  - OBJECTIVE: To identify parents' opinion of the quality of medical information and
      the quality of care in a pediatric intensive care unit (PICU). MATERIAL Y METHOD:
      We designed a structured survey to gather data on the characteristics of
      information given to parents, parents' dealings with the unit's staff and
      resources for parents. This survey was carried out by means of personal direct
      interviews with the parents of 61 children admitted to our PICU from November
      2003 to March 2003. RESULTS: Most of the parents (90.2 %) reported that the
      information they received was of good quality, whereas 3 % did not receive any
      information at all and 8 % only once. A total of 83.6 % were satisfied with the
      unit's staff, whereas 50.8 % pointed out at least one deficiency in the PICU
      resources available for families. Eighty-seven percent of the parents wanted more
      time to be with their child in the PICU. Eighty-four percent of parents reported
      that they had been particularly worried in one or more occasion during their
      child's stay in the PICU and 47 % would occasions liked to have received some
      type of psychological help. CONCLUSIONS: In our PICU the parents of admitted
      children were satisfied with the quality of information and the unit's medical
      staff. Nevertheless, we identified some features that could be improved such as
      the information provided in the first few hours of admission, visiting time
      schedules, psychological support and the unit's infrastructure.

PMID- 15469808
TI  - [Phenotypic consequences of chromosome abnormalities].
AB  - The incidence of chromosome anomalies in newborn infants is 0.7-0.8 %. The
      phenotypic manifestations of chromosomal abnormalities are highly diverse. These
      anomalies may be present in phenotypically normal individuals in whom they can
      increase the risk of recurrent miscarriage and birth defects and/or mental
      retardation. It is important to determine this risk to provide patients with
      appropriate genetic counseling.

PMID- 15469809
TI  - [Scientific information in pediatrics: utility of Indice Medico Espanol].
AB  - The international bibliographic databases (Medline, Embase, Current Contents,
      etc.) are one of the main sources of information in medicine. Because only some
      Spanish journals are included in these databases, knowledge and use of the Indice
      Medico Espanol (IME) is also important because this database includes almost all
      Spanish biomedical and scientific journals (basic, experimental and clinical),
      which provides certain well known advantages for authors and editors in Spain. Of
      the journals indexed at any given time in the IME (461 journals), those related
      to pediatrics constitute 5.2 % of the total (24 journals) with a total of 21,006
      documents. Only 34 % of all the pediatrics documents in the IME are included in
      PubMed. The most productive pediatrics journals in the IME are Anales Espanoles
      de Pediatria (8,639, plus 912 registered from 2002 as Anales de Pediatria),
      Revista Espanola de Pediatria (2,564), Acta Pediatrica Espanola (2,189), Archivos
      de Pediatria (1,365), Pediatrika (1,314), and Cirugia Pediatrica (685). Anales de
      Pediatria is the third most productive journal in the IME, after Medicina Clinica
      (13,323) and Revista Clinica Espanola (9,603). Overall, pediatrics is the second
      most productive field of research in medicine in Spain after internal medicine. A
      complementary tool of the IME is the hypothetical study of the national and
      international impact factor (IF) of Spanish biomedical journals. The hypothetical
      national IF of Anales de Pediatria (0.334) is noteworthy among Spanish medical
      journals overall and is much higher than those of Acta Pediatrica Espanola
      (0.134), Pediatrika (0.119), Cirugia Pediatrica (0.099) and Revista Espanola de
      Pediatria (0.079). The international IF of Anales de Pediatria (0.372) is higher
      than that of some pediatrics journals included in the Science Citation Index. The
      IME should be included in bibliographic search strategies for scientific
      information in pediatrics as a complement to international databases.

PMID- 15469810
TI  - [Asthma and respiratory syncytial virus. New opportunities for therapeutic
      intervention].
AB  - Numerous studies have described an association between respiratory sincticial
      virus (RSV) infection in infancy and the subsequent development of airway
      hyperresponsiveness (AHR). Besides the exaggerated immune response and the
      abnormal neurogenic mechanisms induced by RSV, recent studies have correlated the
      "persistence" of RSV in the lower respiratory tract with the development of AHR.
      Several investigators have evaluated whether treatment with antiviral or
      immunosuppressive agents could decrease the long term respiratory abnormalities
      induced by RSV. The RSV murine model has allowed us to study the
      immunopathogenesis of RSV-induced AHR. Once the airway obstruction, typical of
      acute disease, is resolved and no virus is longer detected by cell cultures, mice
      progress into a chronic phase characterized by AHR and persistent airway
      inflammation. The use of polymerase chain reaction assay for RSV quantitation has
      demonstrated, quite unexpectedly, the presence of RSV RNA in the lower
      respiratory tract of mice during the chronic phase of the disease. As an example
      of intervention, the administration of an anti-RSV neutralizing antibody
      (palivizumab) was associated with a significant reduction in viral replication,
      pulmonary inflammation and inflammatory cytokines, as well as a significant
      improvement in the pulmonary function both in the acute and chronic phases of the
      disease. Future clinical studies to determine whether therapy with palivizumab
      can prevent the long-term morbidity associated with RSV in children are
      warranted.

PMID- 15469811
TI  - [Recombinant human activated protein C in the treatment of children with
      meningococcal purpura fulminans].
AB  - Meningococcal purpura fulminans (MPF) produces high mortality and morbidity,
      despite appropriate standard therapy. Administration of recombinant human
      activated protein C (rhAPC) has been successfully applied in adults with MPF and
      pediatric studies are under way. We report three pediatric patients with MPF
      treated with rhAPC as compassionate therapy. In two of these patients, positive
      clinical and laboratory effects were observed and both children achieved full
      recovery. The remaining patient died after 36 hours from refractory multiorgan
      failure. No rhAPC-related adverse effects were detected. The reported cases
      highlight the usefulness of rhAPC in children with MPF at least as a rescue
      compassionate treatment. Further clinical trials are needed to better delineate
      its efficacy and administration schedule in children.

PMID- 15469812
TI  - [Deep venous thrombosis: an early manifestation of Behcet's disease in
      childhood].
AB  - Behcet's disease is a multisystemic vasculitis of unknown origin whose classical
      triad is oral and genital ulcers and uveitis. Deep venous thrombosis may
      sometimes be the first manifestation of this disease but is very rare in
      children. We report the case of a 14-year-old boy with deep venous thrombosis of
      the leg and a history of severe aphthous gingivostomatitis, perianal ulcers,
      Henoch-Schonlein purpura, ecchymotic lesions on the lower limbs and intermittent
      swelling of the left ankle. Complementary tests ruled out the main causes of
      thrombosis in children. HLA-B5 and B-51 study proved positive, which, together
      with the patient's history, suggested a diagnosis of Behcet's disease. This
      disease usually presents around the third decade of life and is very unusual in
      children. This case is exceptional because thrombosis as an early manifestation
      of Behcet's disease is very rare in children and because it led to the diagnosis
      of Behcet's disease in our patient.

PMID- 15469813
TI  - [Cutaneous larva migrans].

PMID- 15469814
TI  - [Kawasaki's disease in a 3-month-old infant].

PMID- 15469815
TI  - [Newborn infant with an interlabial cystic mass].

PMID- 15469816
TI  - [Erythematous plaques].

PMID- 15469817
TI  - Recombination mechanisms; fortieth anniversary meeting of the Holliday model.
AB  - The year 2004 marks the fortieth anniversary of the Holliday junction. This
      extraordinary DNA structure, originally proposed by Robin Holliday to explain
      genetic recombination in fungi, now appears to be a pivotal intermediate in many
      aspects of DNA metabolism. In those forty years the Holliday junction has gone
      from a hypothetical structure to models for its atomic structure and
      visualization of its dynamics at the single molecule level.

PMID- 15469818
TI  - Conserved translational frameshift in dsDNA bacteriophage tail assembly genes.
AB  - A programmed translational frameshift similar to frameshifts in retroviral gag
      pol genes and bacterial insertion elements was found to be strongly conserved in
      tail assembly genes of dsDNA phages and to be independent of sequence
      similarities. In bacteriophage lambda, this frameshift controls production of two
      proteins with overlapping sequences, gpG and gpGT, that are required for tail
      assembly. We developed bioinformatic approaches to identify analogous -1
      frameshifting sites and experimentally confirmed our predictions for five
      additional phages. Clear evidence was also found for an unusual but analogous -2
      frameshift in phage Mu. Frameshifting sites could be identified for most phages
      with contractile or noncontractile tails whose length is controlled by a tape
      measure protein. Phages from a broad spectrum of hosts spanning Eubacteria and
      Archaea appear to conserve this frameshift as a fundamental component of their
      tail assembly mechanisms, supporting the idea that their tail genes share a
      common, distant ancestry.

PMID- 15469819
TI  - Expansion and compression of a protein folding intermediate by GroEL.
AB  - The GroEL-GroES chaperonin system is required for the assisted folding of many
      essential proteins. The precise nature of this assistance remains unclear,
      however. Here we show that denatured RuBisCO from Rhodospirillum rubrum populates
      a stable, nonaggregating, and kinetically trapped monomeric state at low
      temperature. Productive folding of this nonnative intermediate is fully dependent
      on GroEL, GroES, and ATP. Reactivation of the trapped RuBisCO monomer proceeds
      through a series of GroEL-induced structural rearrangements, as judged by
      resonance energy transfer measurements between the amino- and carboxy-terminal
      domains of RuBisCO. A general mechanism used by GroEL to push large, recalcitrant
      proteins like RuBisCO toward their native states thus appears to involve two
      steps: partial unfolding or rearrangement of a nonnative protein upon capture by
      a GroEL ring, followed by spatial constriction within the GroEL-GroES cavity that
      favors or enforces compact, folding-competent intermediate states.

PMID- 15469820
TI  - GSK3-mediated BCL-3 phosphorylation modulates its degradation and its
      oncogenicity.
AB  - The oncoprotein BCL-3 is a nuclear transcription factor that activates NF-kappaB
      target genes through formation of heterocomplexes with p50 or p52. BCL-3 is
      phosphorylated in vivo, but specific BCL-3 kinases have not been identified so
      far. In this report, we show that BCL-3 is a substrate for the protein kinase
      GSK3 and that GSK3-mediated BCL-3 phosphorylation, which is inhibited by Akt
      activation, targets its degradation through the proteasome pathway. This
      phosphorylation modulates its association with HDAC1, -3, and -6 and attenuates
      its oncogenicity by selectively controlling the expression of a subset of newly
      identified target genes such as SLPI and Cxcl1. Our results therefore suggest
      that constitutive BCL-3 phosphorylation by GSK3 regulates BCL-3 turnover and
      transcriptional activity.

PMID- 15469821
TI  - An Rb-Skp2-p27 pathway mediates acute cell cycle inhibition by Rb and is retained
      in a partial-penetrance Rb mutant.
AB  - It is believed that Rb blocks G1-S transition by inhibiting expression of E2F
      regulated genes. Here, we report that the effects of E2F repression lag behind
      the onset of G1 cell cycle arrest in timed Rb reexpression experiments. In
      comparison, kinase inhibitor p27Kip1 protein accumulates with a faster kinetics.
      Conversely, Rb knockout leads to faster p27 degradation. Rb interacts with the N
      terminus of Skp2, interferes with Skp2-p27 interaction, and inhibits
      ubiquitination of p27. Disruption of p27 function or expression of the Skp2 N
      terminus prevents Rb from causing G1 arrest. A full-penetrance, inactive Rb
      mutant fails to interfere with Skp2-p27 interaction but, interestingly, a partial
      penetrance Rb mutant that is defective for E2F binding retains full activity in
      inhibiting Skp2-p27 interaction and can induce G1 cell cycle arrest with wild
      type kinetics. These results identify an Rb-Skp2-p27 pathway in Rb function,
      which may be involved in inhibition of tumor progression.

PMID- 15469822
TI  - Drp-1-dependent division of the mitochondrial network blocks intraorganellar Ca2+
      waves and protects against Ca2+-mediated apoptosis.
AB  - By transiently or stably overexpressing the mitochondrial fission factor dynamin
      related protein-1 (Drp-1), we evaluated the role of mitochondrial division in
      organelle Ca2+ homeostasis and apoptotic signaling. Quantitative 3D digital
      microscopy revealed a split mitochondrial network in Drp-1-overexpressing cells
      without changes in cell viability. High-speed mitochondrial [Ca2+] ([Ca2+]m)
      imaging revealed propagating intramitochondrial Ca2+ waves in intact cells, which
      were blocked in the Drp-1-fragmented network, leaving a fraction of individual
      mitochondria without substantial [Ca2+]m elevation. Consequently, in Drp-1
      expressing cells the apoptotic efficacy of ceramide, which causes a Ca2+
      dependent perturbation of mitochondrial structure and function, was drastically
      reduced. Conversely, the sensitivity to staurosporine-induced apoptosis,
      previously shown to be directly triggered by Drp-1-dependent recruitment of
      proapoptotic proteins to mitochondria, was enhanced. These results demonstrate
      that the regulated process of mitochondrial fusion and fission controls the
      spatiotemporal properties of mitochondrial Ca2+ responses and, thus,
      physiological and pathological consequences of cellular Ca2+ signals.

PMID- 15469823
TI  - Endogenous trans-acting siRNAs regulate the accumulation of Arabidopsis mRNAs.
AB  - Here we describe a set of endogenous short interfering RNAs (siRNAs) in
      Arabidopsis, some of which direct the cleavage of endogenous mRNAs. These siRNAs
      correspond to both sense and antisense strands of a noncoding RNA (At2g27400)
      that apparently is converted to double-stranded RNA and then processed in 21 nt
      increments. These siRNAs differ from previously described regulatory small RNAs
      in two respects. First, they require components of the cosuppression pathway
      (RDR6 and SGS3) and also components of the microRNA (miRNA) pathway (AGO1, DCL1,
      HEN1, and HYL1) but not components needed for heterochromatic siRNAs (DCL3 and
      RDR2), another class of endogenous plant siRNAs. Second, these siRNAs repress the
      expression of genes that have little overall resemblance to the genes from which
      they originate, a characteristic previously reported only for miRNAs. The
      identification of this silencing pathway provides yet another dimension to
      posttranscriptional mRNA regulation in plants.

PMID- 15469824
TI  - CK2 phosphorylation of Bdp1 executes cell cycle-specific RNA polymerase III
      transcription repression.
AB  - RNA polymerase III (pol III) transcription from the human U6 snRNA promoter can
      be reconstituted with the recombinant factors SNAPc and Brf2-TFIIIB combined with
      purified pol III. In this system, CK2 treatment of the pol III complex is
      required for transcription, whereas treatment of Brf2-TFIIIB is inhibitory. Here
      we show that CK2 inhibits Brf2-TFIIIB by specifically phosphorylating its Bdp1
      component. Bdp1 is phosphorylated by CK2 during mitosis, and this is accompanied
      by Bdp1 dissociation from the U6 promoter and from chromatin in general and by
      transcription repression. Remarkably, whereas inhibition of CK2 in mitotic
      extracts restores pol III transcription, inhibition of CK2 in active S phase
      extracts debilitates transcription. Thus, CK2 is directed to phosphorylate
      different targets within the basal pol III transcription machinery at different
      times during the cell cycle, with opposite transcriptional effects.

PMID- 15469825
TI  - Human SirT1 interacts with histone H1 and promotes formation of facultative
      heterochromatin.
AB  - We characterized human SirT1, one of the human homologs of the budding yeast
      Sir2p, an NAD+-dependent histone deacetylase involved in establishing repressive
      chromatin and increased life span. SirT1 deacetylates histone polypeptides with a
      preference for histone H4 lysine 16 (H4-K16Ac) and H3 lysine 9 (H3-K9Ac) in
      vitro. RNAi-mediated decreased expression of SirT1 in human cells causes
      hyperacetylation of H4-K16 and H3-K9 in vivo. SirT1 interacts with and
      deacetylates histone H1 at lysine 26. Using an inducible system directing
      expression of SirT1 fused to the Gal4-DNA binding domain and a Gal4-reporter
      integrated in euchromatin, Gal4-SirT1 expression resulted in the deacetylation of
      H4-K16 and H3-K9, recruitment of H1 within the promoter vicinity, drastically
      reduced reporter expression, and loss of H3-K79 methylation, a mark restricting
      silenced chromatin. We propose a model for SirT1-mediated heterochromatin
      formation that includes deacetylation of histone tails, recruitment and
      deacetylation of histone H1, and spreading of hypomethylated H3-K79 with
      resultant silencing.

PMID- 15469826
TI  - AlkB restores the biological function of mRNA and tRNA inactivated by chemical
      methylation.
AB  - Deleterious 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) lesions are
      introduced into nucleic acids by methylating agents. It was recently demonstrated
      that the E. coli AlkB protein and a human homolog, hABH3, can demethylate these
      lesions both in DNA and RNA. To elucidate the biological significance of the RNA
      repair, we have tested whether such repair can rescue the function of chemically
      methylated RNA. We demonstrate that a methylation-induced block in translation of
      an mRNA can be readily relieved by treatment with AlkB and hABH3 prior to
      translation. Furthermore, we show that chemical methylation of tRNAPhe inhibits
      aminoacylation and translation, but that the inhibition can be reversed by AlkB
      and hABH3. AlkB-mediated repair of 1-meA in tRNA was also observed in E. coli in
      vivo. Our data demonstrate that AlkB proteins can mediate functional recovery of
      RNA exposed to methylation damage, supporting the notion that RNA repair is
      important.

PMID- 15469827
TI  - Hot spots for modulating toxicity identified by genomic phenotyping and
      localization mapping.
AB  - DNA repair and checkpoint pathways protect against carcinogen-induced toxicity.
      Here, we describe additional, equally protective pathways discovered by
      interrogating 4,733 yeast proteins for their ability to diminish toxicity induced
      by four known carcinogens. A computational mapping strategy for global phenotypic
      data was developed to build a systems toxicology model detailing recovery from
      carcinogen exposure and identifying protein complexes that modulate toxicity.
      Global phenotypic data were merged with global subcellular localization and
      protein interactome data to generate an integrated picture of cellular recovery
      after carcinogen exposure. Statistically validated results from this systems-wide
      integration demonstrate that, in addition to the nucleus, subnetworks of toxicity
      modulating proteins were overrepresented in the vacuolar membrane, endosome,
      endoplasmic reticulum, and mitochondrion. In addition, we show that many proteins
      associated with RNA polymerase II, macromolecular trafficking, and vacuole
      function can now be counted among the many proteins that modulate carcinogen
      induced toxicity.

PMID- 15469828
TI  - Solution structure of the Tn3 resolvase-crossover site synaptic complex.
AB  - Tn3 resolvase is a site-specific DNA recombinase, which catalyzes strand exchange
      in a synaptic complex containing twelve resolvase subunits and two res sites.
      Hyperactive mutants of resolvase can form a simpler complex (X synapse)
      containing a resolvase tetramer and two shorter DNA segments at which strand
      exchange takes place (site I). We have solved the low-resolution solution
      structure of the purified, catalytically competent X synapse from small-angle
      neutron and X-ray scattering data, using methods in which the data are fitted
      with models constructed by rigid body transformations of a published
      crystallographic structure of a resolvase dimer bound to site I. Our analysis
      reveals that the two site I fragments are on the outside of a resolvase tetramer
      core and provides some information on the quaternary structure of the tetramer.
      We discuss implications of our structure for the architecture of the natural
      synaptic complex and the mechanism of strand exchange.

PMID- 15469829
TI  - Delivery of yeast telomerase to a DNA break depends on the recruitment functions
      of Cdc13 and Est1.
AB  - The yeast single-strand TG-repeat telomere binding protein Cdc13 and the
      telomerase accessory protein Est1 play essential roles in chromosome end
      replication. To determine whether a proposed Cdc13-Est1 interaction recruits
      telomerase (Est2), we used a simplified system in which telomere formation was
      monitored at an HO-induced DNA double-strand break (DSB). Tethering of either
      Cdc13 or Est1 adjacent to a DSB promoted telomere formation, and tethering of
      Est1, even in the absence of a DSB, resulted in the recruitment of Est2. Est1
      association with a DSB containing an adjacent short TG-repeat sequence depended
      on the Cdc13-Est1 interaction affected by cdc13-2 and est1-60 mutations, whereas
      Cdc13 association did not. Similarly, Est2 binding to the DSB also required the
      Cdc13-Est1 interaction, but not synthesis of new TG repeats at the break site.
      These data demonstrate a critical role for Est1 in recruiting telomerase to its
      site of action, in cooperation with the telomere binding protein Cdc13.

PMID- 15469830
TI  - ChIC and ChEC; genomic mapping of chromatin proteins.
AB  - To map the genomic interaction sites of chromatin proteins, two related methods
      were developed and experimentally explored in Saccharomyces cerevisiae. The ChIC
      method (chromatin immunocleavage) consists of tethering a fusion protein (pA-MN)
      consisting of micrococcal nuclease (MN) and staphylococcal protein A to
      specifically bound antibodies. The nuclease is kept inactive during the tethering
      process (no Ca2+). The ChEC method (chromatin endogenous cleavage) consists of
      expressing fusion proteins in vivo, where MN is C-terminally fused to the
      proteins of interest. The specifically tethered nucleases are activated with Ca2+
      ions to locally introduce double-stranded DNA breaks. We demonstrate that ChIC
      and ChEC map proteins with a 100-200 bp resolution and excellent specificity. One
      version of the method is applicable to formaldehyde-fixed nuclei, another to
      native cells with comparable results. Among various model experiments, these
      methods were used to address the conformation of yeast telomeres.

PMID- 15469831
TI  - The structure of an endosomal protein sorter.
AB  - Three "endosomal sorting complexes required for transport," ESCRT-I, -II, and 
      III, mediate sorting of ubiquitinated membrane proteins into intraluminal
      endosomal vesicles that are destined for degradation in lysosomes. Two recent
      reports, one in Nature and one in this issue of Developmental Cell, reveal the
      crystal structure of the yeast form of ESCRT-II.

PMID- 15469832
TI  - Caveolae meet endosomes: a stable relationship?
AB  - The endocytic trafficking of caveolae has been the subject of some controversy
      for many years. A new study (Pelkmans et al.) shows that budded caveolae can
      interact with both the caveosome and the early endosome and that caveolin
      enriched regions of the early endosomal membrane form unusually stable domains
      that can incorporate cargo in a regulated manner.

PMID- 15469833
TI  - Untangling the web: mitochondrial fission and apoptosis.
AB  - Mitochondria exist as an interconnected network that is constantly remodeled by
      balancing membrane fission and fusion events. A new study by Szabadkai et al. in
      the October 8th issue of Molecular Cell shows that dynamin-related protein 1
      (Drp1)-induced scission hinders the ability of mitochondria to transport calcium
      across the cell and mediate apoptosis.

PMID- 15469834
TI  - Ena/VASP family: new partners, bigger enigma.
AB  - Linking external signals to remodeling of the cytoskeleton is essential to
      multiple processes during animal development and physiology. Two new studies have
      uncovered a new family of proteins that can regulate actin dynamics both locally
      at the membrane interface and globally throughout the cell.

PMID- 15469836
TI  - Developmental biology is "Cruzing".
AB  - The 2004 Santa Cruz Developmental Biology Meeting took place August 5th-8th and
      covered a diverse range of current topics in developmental biology. This report
      discusses some of the highlights.

PMID- 15469835
TI  - Diverse roles of eph receptors and ephrins in the regulation of cell migration
      and tissue assembly.
AB  - Eph receptor tyrosine kinases and ephrins have key roles in regulation of the
      migration and adhesion of cells required to form and stabilize patterns of cell
      organization during development. Activation of Eph receptors or ephrins can lead
      either to cell repulsion or to cell adhesion and invasion, and recent work has
      found that cells can switch between these distinct responses. This review will
      discuss biochemical mechanisms and developmental roles of the diverse cell
      responses controlled by Eph receptors and ephrins.

PMID- 15469837
TI  - In memoriam: Edward B. Lewis (1918-2004).

PMID- 15469838
TI  - Apoptotic cells can induce compensatory cell proliferation through the JNK and
      the Wingless signaling pathways.
AB  - In many metazoans, damaged and potentially dangerous cells are rapidly eliminated
      by apoptosis. In Drosophila, this is often compensated for by extraproliferation
      of neighboring cells, which allows the organism to tolerate considerable cell
      death without compromising development and body size. Despite its importance, the
      mechanistic basis of such compensatory proliferation remains poorly understood.
      Here, we show that apoptotic cells express the secretory factors wingless (wg)
      and decapentaplegic (dpp). When cells undergoing apoptosis were kept alive with
      the caspase inhibitor p35, excessive nonautonomous cell proliferation was
      observed. Significantly, wg signaling is necessary and, at least in some cells,
      also sufficient for mitogenesis under these conditions. Finally, we provide
      evidence that the DIAP1 antagonists reaper and hid can activate the JNK pathway
      and that this pathway is required for inducing wg and cell proliferation. These
      findings support a model where apoptotic cells activate signaling cascades for
      compensatory proliferation.

PMID- 15469839
TI  - Opposing activities of Dally-like glypican at high and low levels of Wingless
      morphogen activity.
AB  - The glypican family of heparan sulfate proteoglycans has been implicated in
      formation of morphogen gradients. Here, we examine the role of the glypican Dally
      like protein (Dlp) in shaping the Wingless gradient in the Drosophila wing disc.
      Surprisingly, we find that Dlp has opposite effects at high and low levels of
      Wingless. Dlp promotes low-level Wingless activity but reduces high-level
      Wingless activity. We present evidence that the Wg antagonist Notum acts to
      induce cleavage of the Dlp glypican at the level of its GPI anchor, which leads
      to shedding of Dlp. Thus, spatially regulated modification of Dlp by Notum
      employs the ligand binding activity of Dlp to promote or inhibit signaling in a
      context-dependent manner. Notum-induced shedding of Dlp could convert Dlp from a
      membrane-tethered coreceptor to a secreted antagonist.

PMID- 15469840
TI  - Spatial regulation of Wingless morphogen distribution and signaling by Dally-like
      protein.
AB  - Wingless (Wg) is a morphogen required for the patterning of many Drosophila
      tissues. Several lines of evidence implicate heparan sulfate-modified
      proteoglycans (HSPGs) such as Dally-like protein (Dlp) in the control of Wg
      distribution and signaling. We show that dlp is required to limit Wg levels in
      the matrix, contrary to the expectation from overexpression studies. dlp mutants
      show ectopic activation of Wg signaling at the presumptive wing margin and a
      local increase in extracellular Wg levels. dlp somatic cell clones disrupt the
      gradient of extracellular Wg, producing ectopic activation of high threshold Wg
      targets but reducing the expression of lower threshold Wg targets where Wg is
      limiting. Notum encodes a secreted protein that also limits Wg distribution, and
      genetic interaction studies show that dlp and Notum cooperate to restrict Wg
      signaling. These findings suggest that modification of an HSPG by a secreted
      hydrolase can control morphogen levels in the matrix.

PMID- 15469841
TI  - R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is required
      for Xenopus myogenesis.
AB  - We have carried out a small pool expression screen for modulators of the Wnt/beta
      catenin pathway and identified Xenopus R-spondin2 (Rspo2) as a secreted activator
      of this cascade. Rspo2 is coexpressed with and positively regulated by Wnt
      signals and synergizes with Wnts to activate beta-catenin. Analyses of functional
      interaction with components of the Wnt/beta-catenin pathway suggest that Rspo2
      functions extracellularly at the level of receptor ligand interaction. In
      addition to activating the Wnt/beta-catenin pathway, Rspo2 overexpression blocks
      Activin, Nodal, and BMP4 signaling in Xenopus, raising the possibility that it
      may negatively regulate the TGF-beta pathway. Antisense Morpholino experiments in
      Xenopus embryos and RNAi experiments in HeLa cells reveal that Rspo2 is required
      for Wnt/beta-catenin signaling. In Xenopus embryos depleted of Rspo2, the muscle
      markers myoD and myf5 fail to be activated and later muscle development is
      impaired. Thus, Rspo2 functions in a positive feedback loop to stimulate the
      Wnt/beta-catenin cascade.

PMID- 15469842
TI  - Small wing PLCgamma is required for ER retention of cleaved Spitz during eye
      development in Drosophila.
AB  - The Drosophila EGF receptor ligand Spitz is cleaved by Rhomboid to generate an
      active secreted molecule. Surprisingly, when a cleaved variant of Spitz (cSpi)
      was expressed, it accumulated in the ER, both in embryos and in cell culture. A
      cell-based RNAi screen for loss-of-function phenotypes that alleviate ER
      accumulation of cSpi identified several genes, including the small wing (sl) gene
      encoding a PLCgamma. sl mutants compromised ER accumulation of cSpi in embryos,
      yet they exhibit EGFR hyperactivation phenotypes predominantly in the eye. Spi
      processing in the eye is carried out primarily by Rhomboid-3/Roughoid, which
      cleaves Spi in the ER, en route to the Golgi. The sl mutant phenotype is
      consistent with decreased cSpi retention in the R8 cells. Retention of cSpi in
      the ER provides a novel mechanism for restricting active ligand levels and hence
      the range of EGFR activation in the developing eye.

PMID- 15469843
TI  - Differential requirements for COPI transport during vertebrate early development.
AB  - The coatomer vesicular coat complex is essential for normal Golgi and secretory
      activities in eukaryotic cells. Through positional cloning of genes controlling
      zebrafish notochord development, we found that the sneezy, happy, and dopey loci
      encode the alpha, beta, and beta' subunits of the coatomer complex. Export from
      mutant endoplasmic reticulum is blocked, Golgi structure is disrupted, and mutant
      embryos eventually degenerate due to widespread apoptosis. The early embryonic
      phenotype, however, demonstrates that despite its "housekeeping" functions,
      coatomer activity is specifically and cell autonomously required for normal
      chordamesoderm differentiation, perinotochordal basement membrane formation, and
      melanophore pigmentation. Hence, differential requirements for coatomer activity
      among embryonic tissues lead to tissue-specific developmental defects. Moreover,
      we note that the mRNA encoding alpha coatomer is strikingly upregulated in
      notochord progenitors, and we present data suggesting that alpha coatomer
      transcription is tuned to activity- and cell type-specific secretory loads.

PMID- 15469844
TI  - ESCRT-II, an endosome-associated complex required for protein sorting: crystal
      structure and interactions with ESCRT-III and membranes.
AB  - ESCRT-I, -II, and -III protein complexes are sequentially recruited to endosomal
      membranes, where they orchestrate protein sorting and MVB biogenesis. In
      addition, they play a critical role in retrovirus budding. Structural
      understanding of ESCRT interaction networks is largely lacking. The 3.6 A
      structure of the yeast ESCRT-II core presented here reveals a trilobal complex
      containing two copies of Vps25, one copy of Vps22, and the C-terminal region of
      Vps36. Unexpectedly, the entire ESCRT-II core consists of eight repeats of a
      common building block, a "winged helix" domain. Two PPXY-motifs from Vps25 are
      involved in contacts with Vps22 and Vps36, and their mutation leads to ESCRT-II
      disruption. We show that purified ESCRT-II binds directly to the Vps20 component
      of ESCRT-III. Surprisingly, this binding does not require the protruding N
      terminal coiled-coil of Vps22. Vps25 is the chief subunit responsible for Vps20
      recruitment. This interaction dramatically increases binding of both components
      to lipid vesicles in vitro.

PMID- 15469845
TI  - Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of
      lamellipodial dynamics.
AB  - Lamellipodial protrusion is regulated by Ena/VASP proteins. We identified
      Lamellipodin (Lpd) as an Ena/VASP binding protein. Both proteins colocalize at
      the tips of lamellipodia and filopodia. Lpd is recruited to EPEC and Vaccinia,
      pathogens that exploit the actin cytoskeleton for their own motility. Lpd
      contains a PH domain that binds specifically to PI(3,4)P2, an asymmetrically
      localized signal in chemotactic cells. Lpd's PH domain can localize to ruffles in
      PDGF-treated fibroblasts. Lpd overexpression increases lamellipodial protrusion
      velocity, an effect observed when Ena/VASP proteins are overexpressed or
      artificially targeted to the plasma membrane. Conversely, knockdown of Lpd
      expression impairs lamellipodia formation, reduces velocity of residual
      lamellipodial protrusion, and decreases F-actin content. These phenotypes are
      more severe than loss of Ena/VASP, suggesting that Lpd regulates other effectors
      of the actin cytoskeleton in addition to Ena/VASP.

PMID- 15469846
TI  - RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1
      induced adhesion.
AB  - The small GTPase Rap1 induces integrin-mediated adhesion and changes in the actin
      cytoskeleton. The mechanisms that mediate these effects of Rap1 are poorly
      understood. We have identified RIAM as a Rap1-GTP-interacting adaptor molecule.
      RIAM defines a family of adaptor molecules that contain a RA-like (Ras
      association) domain, a PH (pleckstrin homology) domain, and various proline-rich
      motifs. RIAM also interacts with Profilin and Ena/VASP proteins, molecules that
      regulate actin dynamics. Overexpression of RIAM induced cell spreading and
      lamellipodia formation, changes that require actin polymerization. In contrast,
      RIAM knockdown cells had reduced content of polymerized actin. RIAM
      overexpression also induced integrin activation and cell adhesion. RIAM knockdown
      displaced Rap1-GTP from the plasma membrane and abrogated Rap1-induced adhesion.
      Thus, RIAM links Rap1 to integrin activation and plays a role in regulating actin
      dynamics.

PMID- 15469847
TI  - Retrotransposons regulate host genes in mouse oocytes and preimplantation
      embryos.
AB  - A comprehensive analysis of transposable element (TE) expression in mammalian
      full-grown oocytes reveals that LTR class III retrotransposons make an
      unexpectedly high contribution to the maternal mRNA pool, which persists in
      cleavage stage embryos. The most abundant transcripts in the mouse oocyte are
      from the mouse transcript (MT) retrotransposon family, and expression of this and
      other TE families is developmentally regulated. Furthermore, TEs act as
      alternative promoters and first exons for a subset of host genes, regulating
      their expression in full-grown oocytes and cleavage stage embryos. To our
      knowledge, this is the first example of TEs initiating synchronous,
      developmentally regulated expression of multiple genes in mammals. We propose
      that differential TE expression triggers sequential reprogramming of the
      embryonic genome during the oocyte to embryo transition and in preimplantation
      embryos.

PMID- 15469848
TI  - Assembling a gene regulatory network for specification of the B cell fate.
AB  - The generation of B lymphocyte precursors is dependent on the combinatorial
      action of the transcription factors PU.1, Ikaros, E2A, EBF, and Pax-5. Loss of
      PU.1 results in a severe reduction in Flk2+, IL-7R+ lymphoid progenitors as well
      as impaired expression of EBF and Pax-5. Restoration of EBF expression
      facilitates rapid generation of pro-B cells from PU.1-/- progenitors. Molecular
      analysis suggests that PU.1 directly participates in regulation of the EBF gene.
      Although PU.1 is dispensable for expression of most early B lineage genes, it is
      required for CD45R/B220. Using EBF-/- mutant progenitors, we show that EBF
      induces Pax-5 and the early program of B lineage gene expression. Importantly,
      Pax-5 does not rescue B cell development from either PU.1-/- or EBF-/-
      progenitors. Pax-5 expression and function are contingent on EBF. Based on these
      results, we propose a hierarchical regulatory network for specification and
      commitment to the B cell fate.

PMID- 15469849
TI  - An ear-core interaction regulates the recruitment of the AP-3 complex to
      membranes.
AB  - AP-3 is a heterotetrameric adaptor involved in the biogenesis of lysosome-related
      organelles. The function of AP-3 as an adaptor relies on its ability to bind to
      membranes in an Arf-dependent fashion and to recognize sorting signals in the
      cytosolic tails of the transmembrane cargo. Here, we report an interdomain
      interaction involving the ear domain of the delta subunit and the sigma3 subunit
      of AP-3. This interaction interferes with the binding of AP-3 to Arf but not to
      dileucine-based sorting signals. As a consequence, the delta-ear inhibits the
      recruitment of AP-3 to membranes both in vitro and in vivo and impairs the
      sorting of lysosomal membrane proteins. These observations suggest a new
      regulatory mechanism for the recruitment of AP-3 to membranes involving delta-ear
      sigma3 interactions.

PMID- 15469850
TI  - Advances in the clinical laboratory detection of gestational trophoblastic
      disease.
AB  - BACKGROUND: Gestational trophoblastic disease (GTD) consists of a spectrum of
      disorders that are characterized by an abnormal proliferation of trophoblastic
      tissue. Gestational trophoblastic neoplasia (GTN) refers to a subset of GTD with
      a persistently elevated serum hCG in the absence of a normal pregnancy and with a
      history of normal or abnormal pregnancy. Although previously a lethal disease,
      GTN is considered today the most curable gynecologic cancer. However, a delay in
      the diagnosis may increase the patient's risk of developing malignant GTN, and
      therefore the prompt identification of GTN is important. SERUM MARKERS: hCG test
      is essential for detection of GTN. It has emerged that there are problems with
      hCG tests. In addition to regular hCG, at least five major variants of hCG are
      present in serum samples. False-positive hCG (phantom hCG) can occur in the
      absence of GTN. Low-level real hCG may occasionally persist in the absence of
      clinical evidence of pregnancy or GTD. Alternatively, low-level real hCG may be
      due to pituitary hCG. Other placental hormones, human placental lactogen (hPL),
      inhibin and activin, and progesterone have also been evaluated as tumor markers
      for GTD. CONCLUSION: hCG has high diagnostic sensitivity, approaching 100%
      sensitivity, for managing the treatment of GTN and for detecting recurrences of
      disease. It is recommended to use hCG test that recognizes all forms of the hCG
      molecule. In cases where low-level hCG persists, it must be differentiated
      whether it is real or false. Real-hCG may be due to quiescent gestational
      trophoblastic disease or pituitary hCG. It has not yet been established whether
      measurement of markers other than hCG (hPL, inhibin, activin, and progesterone)
      is useful in the detection and follow-up of GTD.

PMID- 15469851
TI  - Alpha-fetoprotein in the early neonatal period--a large study and review of the
      literature.
AB  - BACKGROUND: Alpha-fetoprotein (AFP) is a glycoprotein molecule, which has
      similarity to albumin and is produced by the fetal liver. Its biological role is
      unclear and factors that may influence its concentrations in neonates are only
      partially identified. However, it has an important role as a diagnostic marker,
      especially in certain tumors and liver diseases of childhood. Its normal
      reference values in newborns have not been well defined. METHODS: Serum AFP
      concentrations were measured and characterized in 260 term and near-term newborns
      [gestational age (GA)> or =34 weeks, birthweight (BW)> or =1700 g] at birth
      [umbilical cord (UC) blood] and upon discharge from the nursery at 60+/-24 h of
      life (venous sample). RESULTS: Due to the nonnormal distribution of AFP levels,
      it is useful to relate to reference interval for AFP concentrations at birth that
      was 15.7-146.5 microg/ml, based on 95% confidence interval (CI). The median value
      of 48.3 microg/ml is also a useful reference. However, mean AFP concentrations at
      birth that were 61.6+/-44.8 microg/ml are less informative due to the large
      standard deviation (S.D.). Upon discharge, AFP concentrations dropped to 9.7
      111.9 microg/ml (95% CI) with a median of 34.2 microg/ml. A significant negative
      correlation was found between AFP serum levels and gestational age and to a
      lesser extent with birthweight. No significant differences were found between
      males and females. CONCLUSIONS: Normal reference intervals for AFP in term and
      near-term newborns have been defined, but need to be addressed with caution due
      to the wide range of normal values. AFP levels at birth decrease as gestation
      advances and the newborn weighs more.

PMID- 15469852
TI  - Natriuretic peptides BNP and NT-pro-BNP: established laboratory markers in
      clinical practice or just perspectives?
AB  - A growing body of literature describes diagnostic and prognostic value of B-type
      natriuretic peptides (BNP) in cardiac diseases since it was first described in
      1988. As BNP is mainly secreted in the left ventricular (LV) myocardium, BNP was
      found to reflect LV function much better than any other neurohumoral factor.
      Thus, BNP is recommended as the first noninvasive blood test for determination of
      cardiac function by some authors. The introduction of fully automated, rapid
      bioassays for measurement of BNP and the aminoterminal part of its pro-hormone
      (NT-pro-BNP) made it possible to use the test even in emergency care settings.
      Here we review the literature with special focus on assessment of BNP and NT-pro
      BNP in the following clinical settings: community screening for LV dysfunction,
      primary diagnosis of heart failure in general practice and emergency department
      (ED) and risk stratification in cardiac dysfunction and acute coronary syndromes.
      In addition, we discuss which applications can be recommended for daily clinical
      use from the cardiologist's point of view.

PMID- 15469853
TI  - Clinical significance of circulating endothelial adhesion molecules (sE-selectin
      and sICAM) in untreated multiple myeloma patients.
AB  - BACKGROUND: The expression of adhesion molecules is important for the interaction
      of myeloma cells with the bone marrow microenvironment. In the current study,
      serum soluble adhesion molecules (sICAM-1 and sE-selectin) were measured in
      untreated multiple myeloma (MM) patients in relation with other markers of
      disease activity. MATERIALS AND METHODS: The study group consisted of 67 patients
      with MM (classified according to the Durie-Salmon classification) and 15
      controls. Interleukin-6 (IL-6), sICAM-1 and sE-selectin concentrations were
      determined by enzyme-linked immunosorbent assay (ELISA). In addition, the
      monoclonal protein, erythrocyte sedimentation rate (ESR) and hemoglobin (Hb)
      concentration were also determined. RESULTS: Serum sICAM-1 level increased
      significantly at advanced stages of MM and was higher in comparison to controls
      (p<0.01). sE-selectin increased significantly with advancing stage of the
      disease, but did not differ from controls. IL-6, ESR and M-component were
      significantly higher and Hb concentrations lower with advancing stage of disease.
      There was a positive correlation of IL-6 with sICAM-1 and sE-selectin.
      CONCLUSIONS: We conclude that serum sICAM-1 differs in multiple myeloma patients
      from normals and together with sE-selectin increase in parallel to increasing
      stage of disease, which may reflect a dysregulation and possible involvement of
      these adhesion molecules in myeloma progression.

PMID- 15469854
TI  - High glutathione turnover in human cell lines revealed by acivicin inhibition of
      gamma-glutamyltranspeptidase and the effects of thiol-reactive metals during
      acivicin inhibition.
AB  - BACKGROUND: Glutathione is the most abundant nonprotein sulfhydryl-containing
      compound and constitutes the largest component of the endogenous thiol buffer.
      Glutathione is known to have multifaceted physiological functions and is a
      critical factor in protecting organisms against toxicity and disease.
      Intracellular cysteine concentration is a limiting factor for glutathione
      synthesis. METHODS: In the present study, the metabolism of intra- and
      extracellular glutathione in HeLa and hepatoma cell cultures is investigated by
      using different transport inhibitors for cellular uptake of cystine/cysteine.
      RESULTS: There exist several ways of cystine/cysteine transport into HeLa and
      hepatoma cells, and inhibition of them decreased intracellular concentration of
      cystine/cysteine and in some cases also of glutathione. It was also shown that a
      large pool of total cell culture glutathione was located extracellularly in both
      HeLa and hepatoma cell cultures when gamma-glutamyltranspeptidase (GT) activity
      was inhibited by acivicin (ACI). Furthermore, the addition of thiol-reactive
      metal ions significantly increased the total amount of glutathione in hepatoma
      cell cultures during acivicin inhibition. Thus, occasional determinations of
      extracellular concentrations of glutathione without GT inhibition strongly
      underestimate the total turnover of glutathione in a cell culture. CONCLUSION:
      This finding has important implications for future research in glutathione
      metabolism and the understanding of its role in human health and disease.

PMID- 15469855
TI  - Acetylsalicylic acid inhibits ATP diphosphohydrolase activity by platelets from
      adult rats.
AB  - BACKGROUND AND METHODS: The in vitro effect of the nonsteroidal anti-inflammatory
      drug, acetylsalicylic acid (ASA), on the extracellular adenine nucleotide
      hydrolysis by intact rat blood platelets was studied. RESULTS: Our results
      demonstrate that aspirin, at final concentrations of 2.0 and 3.0 mM, inhibits ATP
      extracellular hydrolysis in vitro by approximately 17% and 21%, respectively.
      Aspirin, at a final concentration of 3.0 mM, also inhibited in vitro
      extracellular ADP hydrolysis by approximately 41%. The same concentrations of
      this drug, however, did not alter AMP hydrolysis by intact rat blood platelets
      under similar assay conditions. The kinetic analysis demonstrated that the
      inhibition of ADP and ATP hydrolysis by aspirin in rat platelets is of the
      uncompetitive type. CONCLUSION: In this study, we demonstrated an inhibitory
      effect of ASA upon E-NTPDase 3 activity of platelets from adult rats and
      discussed the significance of our findings.

PMID- 15469856
TI  - Increased plasma biotinidase activity in rats with paracetamol-induced acute
      liver injury.
AB  - BACKGROUND: Biotinidase, an enzyme that is synthesized by the liver and secreted
      into the blood, decreases in plasma in both humans and experimental animal liver
      cirrhosis. In overdose conditions, paracetamol is known to cause centrilobular
      necrosis in both humans and experimental animals. We determined if there is any
      alteration in the activity of the enzyme in the plasma and liver of rats after
      subtoxic and toxic doses of paracetamol. METHODS: After 4-, 24-, and 40-h
      treatment of rats with either subtoxic (350 mg/kg body wt) or toxic dose (1000 mg
      per kg) of paracetamol intraperitoneally, biotinidase activity was assayed in the
      liver and plasma along with the albumin concentration and ALT activity. RESULTS:
      After the subtoxic dose of paracetamol, there were no significant change in
      plasma biotinidase activity and liver biotinidase activity was observed at any
      time period after treatment. However, 24 and 40 h after the toxic dose of
      paracetamol, biotinidase activity was decreased in the liver and increased in the
      plasma as compared with the control, when plasma ALT was increased. CONCLUSION:
      The increase in plasma biotinidase activity may serve as an indicator of
      paracetamol-induced acute liver injury in the rat.

PMID- 15469857
TI  - Ionized magnesium in erythrocytes--the best magnesium parameter to observe hypo-
      or hypermagnesemia.
AB  - BACKGROUND: Almost 99% of the body magnesium is inside cells. The concentration
      of intracellular ionized magnesium (iMg) is physiologically relevant. iMg in
      erythrocytes is a new parameter that can help to establish reliable information
      on the functional magnesium status. METHODS: iMg concentration in erythrocytes
      and serum was measured by ion-selective electrode, in clinical analyzer Microlyte
      (KONE). Total magnesium (tMg) concentration was measured by atomic absorption
      spectrometry (AAS). Albumin and total protein concentration were measured
      colorimetrically. RESULTS: In critically ill postoperative patients, the mean of
      albumin, protein and hematocrit concentration was significantly lower compared to
      healthy individuals. Hypomagnesemia was found in 15.9% patients as tMgs, at 22.2%
      as iMgs and 36.5% as iMge. Significant correlations are between iMgs and tMgs or
      iMge and iMgs/tMgs. In dialyzed patients, the mean of hematocrit was
      significantly lower, iMge was significantly higher compared with healthy
      individuals. Significant negative correlations are between iMgs and tMge or
      iMge/tMge and tMge. CONCLUSIONS: iMge is the best magnesium parameter to observe
      hypo- or hypermagnesemia for both groups of patients. The function of magnesium
      is mainly intracellular and intracellular magnesium concentrations can be the
      method to evaluate the magnesium status.

PMID- 15469858
TI  - Arteriovenous carboxyhemoglobin difference is not correlated to TNF-alpha, IL-6,
      PCT, CRP and leukocytes in critically ill patients.
AB  - BACKGROUND: It is still unclear as to whether the paradoxical arteriovenous
      carboxyhemoglobin (COHb) difference found in critical illness may represent a
      novel marker of the acute inflammatory response. We determined whether the
      arterial and central venous COHb concentration or their difference may be
      correlated to classical pro-inflammatory markers. METHODS: Arterial and matched
      central venous blood gases were obtained from non-smoking intensive care patients
      undergoing gastrointestinal surgery, and were correlated with plasma
      concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6),
      procalcitonin (PCT), C-reactive protein (CRP) and leukocytes. RESULTS: No
      correlation was found between arteriovenous COHb difference and the investigated
      pro-inflammatory mediators. While arterial and central venous COHb concentrations
      were positively correlated to plasma concentrations of TNF-alpha (P< or =0.01),
      IL-6 (P<0.05) and PCT (P< or =0.01), they were neither interrelated with PCT nor
      with leukocytes. CONCLUSIONS: Arteriovenous COHb difference does not appear to be
      a marker of the acute inflammatory response. Future studies are needed to
      investigate whether arterial and central venous COHb concentrations by themselves
      may serve as indicators of systemic inflammation.

PMID- 15469859
TI  - Fenofibrate inhibits thrombogenic and fibrinolytic factors expression in adipose
      tissue of atherosclerotic rabbits.
AB  - BACKGROUND: Tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1)
      activity and/or expression are upregulated in obesity. We investigated TF and PAI
      1 mRNA expression in adipose tissues of cholesterol-fed rabbits, and the effects
      of fenofibrate. METHODS: Male rabbits were fed either a normal or high
      cholesterol diet for 8 weeks. After 4 weeks, those fed high-cholesterol diets
      were randomly assigned to 30 mg/kg/day fenofibrate and starch. At the end of 12
      weeks, subcutaneous adipose was collected. The concentration of TF and PAI-1 mRNA
      was detected by reverse transcription-polymerase chain reaction (RT-PCR). The
      plasma activities of TF and PAI-1 were determined with ELISA and chromogenic
      substrate method, respectively. RESULTS: The atherogenic diet caused a consistent
      increase in serum concentrations of total cholesterol (TC) (p<0.05) and did not
      significantly affect serum triglyceride (TG) concentrations, and increased TF and
      PAI-1 mRNA expression in adipose tissues (1.149+/-0.014 and 1.200+/-0.012,
      respectively) as compared to the normal diet (1.034+/-0.011 and 1.098+/-0.013,
      respectively) (p<0.01). The plasma activities of TF [(74.4+/-28.8) ng/l] and PAI
      1 [(15.6+/-1.9) x 10(3) AU/l] in high-cholesterol diet group were higher than
      those of normal diet group [(33.1+/-10.7) ng/l and (6.9+/-0.9) x 10(3) AU/l,
      respectively, p<0.05]. Four-week fenofibrate treatment resulted in significant
      decrease of TF (1.017+/-0.010) and PAI-1 mRNA (1.061+/-0.011, p<0.01), the plasma
      activity of TF [(40.3+/-12.2) ng/l, p<0.05] and PAI-1 [(7.5+/-1.5) x 10(3) AU/l,
      p<0.01] also decreased significantly, and the concentrations of lipids were not
      changed. CONCLUSION: TF and PAI-1 mRNA expression and plasma activities increased
      in adipose tissue of cholesterol-fed rabbits. Fenofibrate reduced TF and PAI-1
      expression and plasma activity in adipose, suggesting that fenofibrate treatment
      reduces thrombosis risk, and may have an antithrombotic effect independent of its
      lipid-lowering.

PMID- 15469860
TI  - Alteration of autoantibodies against p53 in Taiwanese lung cancer patients
      undergoing chemotherapy.
AB  - BACKGROUND: Correlation between p53 autoantibodies (p53 Abs) titers and the
      efficacy of Taiwanese lung cancer patients undergoing chemotherapy has never been
      investigated. Our present study aimed at evaluating putative possibility of using
      p53 Abs levels as a model system to monitor effect of chemotherapy and prognosis
      prediction of lung cancer. METHODS: The prevalence of p53 Abs in lung cancer
      patients and temporal alteration of p53 Abs titers in lung cancer patients
      carrying p53 Abs were investigated by using ELISA and Western blot analysis.
      RESULTS: p53 Abs was detected in 17 of 277 (6.14%) lung cancer patients, the
      positivity of p53 Abs in patients with small cell lung carcinoma and non-small
      cell lung carcinoma was 4.88% and 6.36%, respectively. No significant association
      between p53 Abs and patients' clinical manifestations was found. Titer of p53 Abs
      was decreased in 6 of 17 p53 Abs-carrying patients after chemotherapy. However,
      the decreasing p53 Abs titers were not correlated with patients' survival or
      chemotherapeutic efficacy. CONCLUSIONS: The prevalence of p53 Abs in Taiwanese
      lung cancer is much lower than that in Caucasians. It is unlikely that p53 Abs
      titer could be a monitoring indicator for the chemotherapeutic efficacy or a
      prognosis indicator of lung cancer.

PMID- 15469861
TI  - The regular supplementation with an antioxidant mixture decreases oxidative
      stress in healthy humans. Gender effect.
AB  - BACKGROUND: Antioxidant consumption is claimed to be associated with improved
      antioxidant defenses and with the prevention of free radical-associated diseases.
      We evaluated if the regular supplementation with an antioxidant mixture modified
      oxidative stress parameters in healthy humans. METHODS: Malondialdehyde (MDA),
      vitamin E (alpha-tocopherol), beta-carotene, and ubiquinol-10 were determined in
      plasma by HPLC; plasma 2-thiobarbituric acid reactive substances (TBARS) were
      evaluated fluorometrically. The supplement contained 106 IU vitamin E, 10 mg beta
      carotene, 60 mg coenzyme Q-10, and 40 microg selenium. RESULTS: After a 10-day
      wash out period, 16 healthy, free-living adults (31-48 years old; 9 women, 7 men)
      consumed the supplement daily during 30 days. At day 20, plasma concentration of
      vitamin E (alpha-tocopherol), beta-carotene, and ubiquinol-10 increased 45%, 66%,
      and 104%, respectively, over baseline values. Plasma MDA concentrations were
      reduced at days 20 (25%) and 30 (32%). Plasma TBARS concentrations decreased
      steadily during the treatment, reaching at day 30 an 11% decrease compared to
      baseline. Segregating by gender, both MDA and TBARS plasma concentrations were
      higher in men than in women at baseline. However, such differences disappeared
      after 30 days of supplementation. CONCLUSION: The observed modifications in
      variables associated with oxidative stress are indicative of an effective
      antioxidant action of the used mixture of lipid soluble compounds, and gender
      differences suggest that men should optimize their antioxidants defenses earlier
      in life than women.

PMID- 15469862
TI  - Structural analysis and fatty acid-binding properties of two Croatian variants of
      human serum albumin.
AB  - BACKGROUND: The aim of the present work was to characterize the molecular defects
      of a slow-migrating (albumin Zagreb) and a fast-migrating (albumin Krapina)
      genetic variant of human serum albumin detected in heterozygous persons living in
      Croatia and to elucidate the fatty acid-binding properties of the two
      alloalbumins. METHODS: Purification and structural identification of the variants
      were performed by conventional protein chemistry methods, whereas types and
      amounts of albumin-bound, endogenous fatty acids were determined by gas
      chromatography. RESULTS: Protein sequencing established that albumin Zagreb is a
      proalbumin variant (-1Arg-->Gln), and that albumin Krapina is due to a mutation
      within the mature polypeptide chain (573Lys-->Glu). The gas chromatographic
      results showed that the fatty acid-binding properties of the proalbumin variant
      are normal, while the amino acid substitution in position 573 resulted in a
      general decrease of fatty acid binding. CONCLUSIONS: The structural defects of
      the first alloalbumins, detected by routine clinical electrophoresis among the
      Croatian population, were characterized. Albumin Zagreb is caused by a hot-spot
      mutation occurring in a CpG sequence in the albumin gene. It is commonly assumed
      that bisalbuminaemia has no direct clinical relevance. However, the present study
      suggests that naturally occurring mutations can affect the ligand-binding
      properties of human serum albumin.

PMID- 15469863
TI  - Evaluation of Advia Centaur automated chemiluminescence immunoassay for
      determining total homocysteine in plasma.
AB  - BACKGROUND: A lot of methods are now available for total plasma homocysteine
      (tHcy) determination. HPLC with fluorescence detection were the most widely used
      methods until recently but immunoassays, easier to use, currently supplant in
      house laboratory methods. METHODS: The latest commercial automated
      chemiluminescence immunoassay (ICL) for tHcy, developed on the ADVIA Centaur
      analyzer (Bayer Diagnostics), was fully evaluated and compared with a current
      HPLC method. RESULTS: The ICL-ADVIA Centaur method had a detection limit <0.9
      micromol/l and was linear for tHcy between 2.4 and 58.8 micromol/l. The within-
      and between assay imprecision was <6% and <7%, respectively. The analytical
      recovery ranged from 93.5% to 109.7%. The comparison of 168 clinical plasma
      specimens indicated a good correlation between the two methods (r=0.96, p<0.0001)
      but a systematic positive bias for ICL-ADVIA Centaur method (mean difference=3.0
      micromol/l). CONCLUSIONS: The ADVIA Centaur method is a useful and practicable
      alternative to HPLC methods for tHcy determination. The ICL method is even more
      convenient than chromatographic methods for routine use because of its
      significantly higher throughput (200 samples/h vs. 40 per 24 h). However, the
      agreement among methods is insufficient to allow them to be used interchangeably.

PMID- 15469864
TI  - Comparison of coenzyme Q10 plasma levels in obese and normal weight children.
AB  - BACKGROUND: Childhood obesity is associated with lower plasma levels of
      lipophilic antioxidants which may contribute to a deficient protection of low
      density lipoproteins (LDL). An increased plasma level of oxidized LDL in obese
      people with insulin resistance has been demonstrated. The lipophilic antioxidant
      coenzyme Q10 (CoQ10) is known as an effective inhibitor of oxidative damage in
      LDL as well. The aim of the present study was to compare the CoQ10 levels in
      obese and normal weight children. METHODS: The CoQ10 plasma concentrations were
      measured in 67 obese children (BMI>97th percentile) and related to their degree
      of insulin resistance. Homeostasis model assessment (HOMA) was used to detect the
      degree of insulin resistance. The results were compared to a control group of 50
      normal weight and apparently healthy children. The results of the CoQ10 levels
      were related to the plasma cholesterol concentrations. RESULTS: After adjustment
      to plasma cholesterol, no significant difference in the CoQ10 levels between
      obese and normal weight children could be demonstrated. Furthermore, there was no
      difference between insulin-resistant and non-insulin-resistant obese children.
      CONCLUSION: CoQ10 plasma levels are not reduced in obese children and are not
      related to insulin resistance.

PMID- 15469865
TI  - The influence of tumor necrosis factor -308 and C-reactive protein G1059C gene
      variants on serum concentration of C-reactive protein: evidence for an age
      dependent association.
AB  - BACKGROUND: C-reactive protein (CRP) synthesis and activity are modulated both by
      genetic and environmental factors. Data about the influence of genetic factors
      upon CRP concentration are sparse. We evaluated the hypothesis that allele
      variations in the genes encoding the CRP and TNF-alpha genes could modulate hs
      CRP serum concentration in the general population. METHODS: Six hundred and
      eighty-four asymptomatic Brazilian individuals, selected between July 1998 and
      July 2001, 295 men (43.1%) and 389 women (56.9%) were studied. Laboratory
      assessment included: serum glucose, cholesterol, triglycerides, thyroid
      stimulating hormone, uric acid and CRP measured by a high-sensitivity assay (hs
      CRP). TNF -308 and CRP G1059C genotypes were obtained through PCR amplification
      and restriction enzyme digestion. RESULTS: Serum concentrations of hs-CRP were
      distributed into population quartiles. There was no significant difference of hs
      CRP serum concentration regarding CRP gene G1059C polymorphism. However, there
      was a tendency for higher hs-CRP serum levels in individuals harboring the TNFA2
      allele in quartile 4. In addition, ANOVA factorial modeling using log-transformed
      hs-CRP serum level as the dependent variable disclosed a significant association
      between hs-CRP and the TNFA2 allele following stratification for age quartiles
      (p=0.01). Finally, the presence of TNFA2 allele in this age group increased the
      odds of being in the fourth quartile of hs-CRP concentration (p<0.05, OR=5.1).
      CONCLUSION: These findings suggest an association between a functional genetic
      variant of the TNF-alpha gene and hs-CRP levels at particular age groups.

PMID- 15469866
TI  - Accuracy of the EasyTouch blood glucose self-monitoring system: a study of 516
      cases.
AB  - BACKGROUND: Self-monitoring blood glucose device is an important tool for
      diabetes patients to efficiently control their blood glucose concentrations. We
      evaluated the accuracy of EasyTouch glucose monitoring system. METHODS: Capillary
      blood glucose concentrations measured using EasyTouch and the reference values
      obtained from Yellow Springs Instruments (YSI) 2300 STAT were performed in the
      Department of Laboratory Medicine, Wei-Gong Memorial Hospital. Results were
      evaluated using (1) linear regression analysis, (2) Clarke Error Grid analysis,
      (3) percentage of readings within a defined range of deviation from the reference
      value, (4) bias plots, and (5) coefficients of variation (CVs) calculated from 60
      measurements in series. RESULTS: The window of the 516 EasyTouch readings covered
      a range from 42 to 555 mg/dl. Linear regression analysis yielded a regression
      slope 0.9972, intercept 1.899 mg/dl, r2 0.9571, and Syx 14.89 mg/dl. A Clarke
      Error Grid analysis showed 100% of the EasyTouch readings in clinically
      acceptable zones A and B. Of the EasyTouch readings, 98.3%, 91.9%, 78.3% and
      46.9% were found within +/-20%, +/-15%, +/-10%, and +/-5%, respectively, of the
      reference values. Further analysis showed that the percentage of EasyTouch
      readings within the defined intervals was similar in three glucose ranges (< or
      =100, 101-200, and > or =201 mg/dl). The CVs for the four lots of strips (lot 1
      to lot 4) ranged from 3.5 to 5.5%, 2.1 to 4.8%, 1.8 to 3.6%, and 3.0 to 5.7%,
      respectively. CONCLUSIONS: EasyTouch provides high accurate and precise glucose
      readings over a wide range of glucose concentrations.

PMID- 15469867
TI  - Heritability of biochemical kidney markers and relation to survival in the
      elderly--results from a Danish population-based twin study.
AB  - BACKGROUND AND AIM: We performed a twin study to assess the relative contribution
      of genetic and environmental factors to serum levels of urea, creatinine, urate
      and sodium in a population of 688 elderly twins (73-95 years). Furthermore, we
      tested the association between these biochemical values and mortality to examine
      the consequence of an abnormal biochemical kidney parameter in an aging
      population. RESULTS: A third to a half of the variation in the biochemical kidney
      tests is due to genetic factors except for creatinine in males. Survival analysis
      show that all four parameters influence mortality and values below reference
      interval for urea and urate have a more pronounced impact on survival [hazard
      ratios (95% confidence interval): 2.32 (1.03-5.26) and 3.56 (1.46-8.69),
      respectively] than values above [1.20 (0.87-1.64) and 1.50 (1.11-2.02),
      respectively]. Increased creatinine (above 130 micromol/l) and decreased sodium
      (below 136 mmol/l) also have a significant impact on survival with hazard ratios
      on 1.83 (1.13-2.95) and 1.56 (1.22-1.99), respectively. Between 5% and 44% of the
      measured values are outside the established reference interval. CONCLUSION: This
      study provides evidence for the importance of genetic factors in determining the
      biochemical kidney parameters in an aging population. Furthermore, our data shows
      that abnormal kidney parameters are common in older adults and results in a
      significant increase in mortality risk.

PMID- 15469868
TI  - Analytical variation in the measurement of serum monoclonal component by
      capillary electrophoresis.
AB  - The amount of serum monoclonal components (MC), and moreover, their variation
      with time are important factors for differentiating malignancy-associated from
      benign gammopathies. Capillary electrophoresis (CE) of serum proteins allows
      better quantitative measurement in comparison to conventional gel-supported
      electrophoresis. We investigated the analytical variation of CE measurement of
      serum MC of different sizes: the variation due to integration settings and the
      analytical variation of the CE procedure were assessed in separate experiments.
      "Small" MC (in the interval 4-14% of total protein) were measured with analytical
      imprecision (CV%) in the interval 5-25%. The step of setting the integration
      limits was found to generate an important portion of such an overall variability.
      The imprecision was negatively, nonlinearly related to MC concentration: at the
      "critical" MC value of 40% of total protein, the analytical imprecision was CV
      approximately 2.5%. The variation computed from sets of subsequent routine MC
      measurements in "stable" patients with MGUS, over observation intervals from 10
      to 30 months, behaved similarly to the "pure" analytical variation measured
      experimentally. This suggested very low, if any, biological variation of MC.
      Differences between subsequent MC measurements in a patient should be interpreted
      in light of the analytical variation.

PMID- 15469869
TI  - Dietary antioxidant lack, impaired hepatic glutathione reserve, and cholesterol
      gallstones.
AB  - BACKGROUND: Theoretical considerations and experimental studies suggest a causal
      connection between micronutrient antioxidant insufficiency and the development of
      human gallstones. METHODS: Fasting plasma/serum samples from 24 patients with
      cholesterol gallstones-on unchanged lifestyles-were analysed for the four main
      micronutrient antioxidants, glutathione and factors that impact or report upon
      glutathione homeostasis. The results were assessed by comparison with laboratory
      referent ranges. RESULTS: The vitamin E:cholesterol ratio was lower in patients
      than controls (P=0.021) as also concentrations of beta-carotene (P=0.001) and
      vitamin C (P=0.001) but not selenium (P=0.280). A fall in plasma glutathione
      (P=0.001) was also accompanied by lower values of pyridoxyl-5-phosphate (the
      coenzyme that participates in vitamin B6-dependent enzyme reactions) which is
      involved in glutathione biosynthesis (P<0.001), and of folate (P=0.012) but not
      vitamin B12 (P=0.377) that participate in its regeneration via the methionine
      homocysteine pathway. Despite these defects, values for plasma homocysteine were
      not significantly different from controls (P=0.092)-an anomaly rationalised by
      poor levels of precursor methionine (P=0.003) and cysteine (P=0.046).
      CONCLUSIONS: Micronutrient antioxidant-including sulphur amino acid-lack, with
      disturbed glutathione homeostasis, are features of cholesterol gallstone disease.

PMID- 15469870
TI  - Gene analysis of the glucocorticoid receptor alpha in Alzheimer's disease.
AB  - BACKGROUND: In Alzheimer's disease (AD), the hypothalamic-pituitary-adrenal (HPA)
      axis is hyperactive and the sensitivity to dexamethasone is decreased, suggesting
      a possible involvement of glucocorticoid receptor alpha (GRalpha) defects in the
      aetiopathology of the disease. METHODS: We, therefore, searched for the presence
      of mutations in the human GRalpha (hGRalpha) gene, focusing on the hormone
      binding domain due to its importance in mediating glucocorticoids' effects. RNA
      isolated from peripheral blood mononuclear cells (PBMCs) of 15 patients with
      Alzheimer's disease and 20 healthy individuals was subjected to reverse
      transcription-polymerase chain reaction amplification (RT-PCR) analysis followed
      by denaturing gradient gel electrophoresis (DGGE). RESULTS: No mutations could be
      detected in the region of the hGRalpha gene examined. CONCLUSIONS: We conclude
      that the hormone-binding domain of GRalpha is not altered in Alzheimer's disease
      and molecular defects in other gene regions of the GRalpha or in its isoform
      GRbeta warrant further investigation in Alzheimer's disease.

PMID- 15469871
TI  - Hypermethylation of the RASSF1A gene in gliomas.
AB  - BACKGROUND: Promoter methylation is an important pathway in transcriptional
      silencing of tumor suppressor genes (TSGs) in brain tumors. The identified 3p21.3
      tumor suppressor gene RAS association domain family protein 1A (RASSF1A) is
      highly methylated in primary lung, breast and other tumors. We investigated the
      promoter methylation and gene expression of RASSF1A in gliomas. METHODS: The
      methylation status of the promoter region of RASSF1A, p16INK4A and death
      associated protein kinase (DAPK) genes was analyzed by methylation-specific PCR
      (MSP) in 41 surgically resected gliomas. RASSF1A expression was also detected by
      reverse-transcription polymerase chain reaction (RT-PCR) in 28 glioma tissues.
      RESULTS: The frequencies of RASSF1A, p16INK4A and DAPK promoter methylation were
      13/41 (31.7%), 3/41 (7.3%) and 6/41 (14.6%) respectively. However, the
      methylations of those genes were not correlated with the clinical characteristics
      of patients (tumor grade, tumor types and sex). Among 28 glioma tissues, 6 showed
      the loss of the gene (21.4%). Promoter hypermethylation of RASSF1A is associated
      with loss of gene expression in glioma tissues. (p=0.022). CONCLUSIONS: Our
      results suggested that the RASSF1A gene might play an important role in glioma
      carcinogenesis. It also gives us an insight for future glioma medical therapy
      with a demethylating agent.

PMID- 15469872
TI  - Trimester-specific reference intervals for thyroxine and triiodothyronine in
      pregnancy in iodine-sufficient women using isotope dilution tandem mass
      spectrometry and immunoassays.
AB  - BACKGROUND: Accurate assessment of the pregnant woman's thyroid status is
      critical, for both the initiation of thyroid hormone therapy and for the
      adjustment of thyroid hormone dose in those already receiving thyroid hormone.
      Trimester-specific intervals are especially important during pregnancy when
      thyroid insufficiency may be associated with adverse obstetric outcome and fetal
      neurodevelopmental deficits. We defined pregnancy-specific reference intervals
      for thyroxine (T4) and 3,5,3'-triiodothyronine (T3). We used a novel isotope
      dilution tandem mass spectrometry (LC/MS/MS) method, and compare these to
      reference intervals obtained by immunoassays (IAs) performed on the same samples.
      METHODS: Concentrations of circulating T4 and T3 were measured simultaneously
      during first, second and third trimesters and postpartum in iodine-sufficient,
      healthy, singleton pregnancies using API-3000 LC/MS/MS with deuterium-labeled
      internal standard (L-thyroxine-d2). Immunoassays were conducted on the same
      samples (T4 Dade Behring RxL, T3 DPC-Immunolite). RESULTS: Linear regression is
      reported for method comparisons; for T4, the slope decreased from r=0.900 in
      nonpregnant women to 0.802-0.820 during pregnancy. For T3, correlations between
      LC/MS/MS and immunoassays were weaker in all cases (r=0.407-0.574). CONCLUSION:
      In this longitudinal study, we established trimester-specific reference intervals
      for T4 and T3 by LC/MS/MS and compare these to intervals obtained by
      immunoassays.

PMID- 15469873
TI  - A simple multiplex PCR method for the concurrent detection of three CYP2C8
      variants.
AB  - BACKGROUND: Cytochrome P450 (CYP) 2C8 is a principle enzyme responsible for the
      metabolism of many clinically important drugs as well as endogenous compounds
      such as arachidonic acid. The enzyme is genetically polymorphic but a simple
      method is not available to study its genetic polymorphism. We developed and
      optimized a variant-specific PCR techniques to detect CYP2C8*2, CYP2C8*3 and
      CYP2C8*4. METHOD: Genomic DNA was extracted from blood using standard extraction
      methods. A two-step PCR method was developed to detect simultaneously three
      CYP2C8 variants. In the first PCR (PCR1), specific regions from exons 3, 5 and 8
      of the CYP2C8 gene were amplified. The products were used as templates in
      parallel alleles-specific PCR (PCR2). This method was tested against DNA samples
      obtained from 57 healthy Malaysian volunteers. RESULT: The bands of interest were
      successfully amplified. This method showed specific and reproducible results when
      tested on healthy volunteers. DNA sequencing further confirmed genotype results
      obtained from current method. CONCLUSION: We have successfully developed and
      optimized a multiplex PCR method suitable for use in population studies of CYP2C8
      polymorphism.

PMID- 15469874
TI  - Prevalence in a Tunisian Arabic population of factor VII DNA variants and
      relation to factor VII plasma levels.
AB  - BACKGROUND: A raised plasma factor VII (FVII) level is a risk factor for coronary
      heart disease. DNA variants have been described to be associated with alteration
      in FVII levels. The prevalence of FVII polymorphisms is unknown in the Tunisian
      Arab population. METHODS: In a group of 240 healthy Tunisians, we examined the
      relationship between levels of FVII coagulant activity (FVIIc) and two
      polymorphisms in the FVII gene. One polymorphism alters arginine at position 353
      to glutamine (R/Q) and the other is a 10 base pair insertion (0/10 bp). RESULTS:
      The FVII distribution was in accordance with the Hardy-Weinberg equilibrium. The
      allele frequencies of Q and 10 bp were 0.212 and 0.235, respectively. There were
      significant differences in these allelic frequencies between Tunisian and other
      populations (p<0.001). We observed lower FVIIc levels among subjects with the Q
      allele compared to RR subjects (RR: 98.17%, RQ/QQ: 57.41%, p<0.0001). For the
      0/10 polymorphism, no statistically difference was observed. CONCLUSION: The
      prevalence of the Q allele which was found to be associated with lower plasma
      FVIIc levels is high in Tunisian population. Further analyses should yield
      information on the protective role of carrying the Q allele for coronary heart
      disease.

PMID- 15469875
TI  - Differential expression of matrix metalloproteinases in viral and non-viral
      chronic liver diseases.
AB  - BACKGROUND: Fibrosis is a common consequence of chronic liver diseases
      irrespective of aetiology. Metalloproteinases play an important role in the
      fibrotic process participating in the balance between collagen synthesis and
      degradation. We examined whether matrix gelatinases and stromelysins are
      similarly involved in the development of viral (HCV, HBV) and non-viral (NASH)
      liver diseases. METHODS: Hepatic mRNA levels of matrix metalloproteinase MMP-2,
      MMP-9, MMP-10 and MMP-11 isolated from liver biopsies were measured by semi
      quantitative RT-PCR. Seventy-three patients were examined in this study: non
      diseased controls (10), patients with chronic hepatitis B (14), chronic hepatitis
      C (33) and non-alcoholic steatohepatitis (16). RESULTS: A significant increase of
      MMP-9 and MMP-10 expression was found in patients with non-viral (non-alcoholic
      steatohepatitis) liver disease. Patients with chronic hepatitis B and hepatitis C
      showed an increase in MMP-2 mRNA expression compared to controls. Moreover,
      chronic hepatitis B and hepatitis C patients had significantly different mRNA
      expression patterns. CONCLUSIONS: These findings indicate that matrix
      metalloproteinases are differentially involved in the fibrotic process of viral
      and non-viral chronic liver diseases. Differences exist between HBV and HCV
      chronic hepatitis. Differences between early and late fibrosis indicate that in
      future studies, careful staging of patients is mandatory for interpretation of
      results.

PMID- 15469876
TI  - Day-night variations of urinary glycosaminoglycans in healthy young men.

PMID- 15469877
TI  - Involvement of alpha7- and alpha4beta2-type postsynaptic nicotinic acetylcholine
      receptors in nicotine-induced excitation of dopaminergic neurons in the
      substantia nigra: a patch clamp and single-cell PCR study using acutely
      dissociated nigral neurons.
AB  - The receptor subtypes, which mediate nicotine-induced excitation of dopaminergic
      neurons in the substantia nigra, were investigated by whole-cell patch clamp
      studies and single-cell RT-PCR using acutely dissociated nigral neurons. Three
      types of current were observed when acetylcholine (1 mM) was applied to the
      neurons in the presence of atropine (1 microM) by the U-tube system, which
      allowed the rapid application of drugs. In 50% of neurons examined, acetylcholine
      (1 mM) plus atropine (1 microM) evoked a current with a rapidly desensitizing
      decay phase (designated as type Ia current). In 14% of neurons tested, the
      current induced by acetylcholine plus atropine had a decay phase with slow
      desensitization (designated as type II current). The third type of response,
      which had both characteristics of type Ia and II currents, was evoked in 36% of
      neurons tested (designated as type Ib currents). Nicotine (1 mM) also induced
      three types of inward currents which were similar to those induced by
      acetylcholine (1 mM) plus atropine (1 microM). In all three types of current,
      nicotine (0.1 microM-1 mM)-evoked inward currents were dose-dependent. Type Ia
      and II currents were inhibited by methyllycaconitine (MLA, 0.01 microM), a
      selective nicotinic alpha7 receptor antagonist, and dihydro-beta-erythroidine
      (DHbetaE, 0.1 microM), an antagonist for alpha4beta2 receptor, respectively. In
      type Ib currents, a fast-decaying phase was inhibited by MLA (0.01 microM), while
      a slow-decaying phase was blocked by DHbetaE (0.1 microM). After recording the
      type Ib current, single-cell RT-PCR analysis was performed using aspirated
      cytoplasm as total RNA templates. The results revealed that mRNAs for alpha7
      nicotinic receptor subunit and tyrosine hydroxylase were detected in the same
      single neuron tested, which confirms the existence of alpha7-type nicotinic
      acetylcholine receptor in dopaminergic neurons of this area. These results
      suggest that nicotine directly acts on postsynaptic alpha7- and alpha4beta2-type
      nicotinic acetylcholine receptors and induces inward current, which result in the
      excitation of dopaminergic neurons in the substantia nigra.

PMID- 15469878
TI  - Conservation of expression and alternative splicing in the prosaposin gene.
AB  - Prosaposin is the precursor of four lysosomal activator molecules known as
      saposins A, B, C and D. It is also secreted and was proposed to be a neurotrophic
      factor. The neurotrophic function was attributed to the amino terminus of saposin
      C. In man, mouse and rat prosaposin is transcribed to two major isoforms
      differing in the inclusion of 9 bps of exon 8 within the saposin B domain. In the
      present study, we show that there is evolutionary conservation of the prosaposin
      structure and alternative splicing in chick and zebrafish as well. Moreover,
      there is conservation in prosaposin expression as tested immunohistochemically in
      the mouse and chick developing brain. We developed a sensitive assay to
      quantitate the prosaposin alternatively spliced forms. Our results indicate that,
      in mouse brain, skeletal and cardiac muscle the exon 8-containing RNA is most
      abundant, while it is almost absent from visceral and smooth muscle-containing
      organs. We observed temporal and differential expression of the alternatively
      spliced prosaposin mRNAs in mouse and chick brain as well as during development.
      The elevation in the abundance of exon 8-containing prosaposin RNA during mouse
      and chick brain development may suggest a role for the exon 8-containing
      prosaposin form in this process.

PMID- 15469879
TI  - Expression profile of mRNAs from rat hippocampus and its application to
      microarray.
AB  - Stress refers to physiological or psychological stimuli that disrupt homeostasis
      and induce pathophysiological conditions due to maladaptive response, sometimes
      resulting in mental disorders including depression and post-traumatic stress
      disorder. Severe stress has been shown to induce neuronal atrophy and apoptosis,
      especially in the hippocampus, which is thought to be a region of the brain
      important in stress-related disorders. We have analyzed gene expression in rat
      hippocampus comprehensively to clarify the molecular mechanism of stress-related
      disorders. In the present study, we identified and catalogued 13,660 partial
      complementary DNA sequences (expressed sequence tags (ESTs)) of randomly selected
      clones from a cDNA library of rat hippocampus. Sequence analysis showed that
      these clones cluster into 7173 non-redundant sequences comprising 1794 clusters
      and 5379 singletons. As a result of nucleotide and peptide database search, 2594
      were found to represent known rat sequences. Of the remaining 4579 genes, 599 non
      redundant ESTs represent rat homologs of genes identified in other species or new
      members of structurally related families. In addition, we illustrate the use of
      these clone sets by constructing a cDNA microarray focused on genes categorized
      into "cell/organism defense". These ESTs and our own microarray thus provide an
      improved genomic source for molecular studies of animal models of stress-related
      disorders.

PMID- 15469880
TI  - Unique levels of expression of N-methyl-D-aspartate receptor subunits and
      neuronal nitric oxide synthase in the rostral ventrolateral medulla of the
      spontaneously hypertensive rat.
AB  - The rostral ventrolateral medulla (RVLM) is the major brainstem region
      contributing to sympathetic control of blood pressure. We have compared the
      expression of N-methyl-d-aspartate (NMDA) receptor subunits (NR1, NR2A-D), NR1
      splice variants (NR1-1a/1b, -2a/2b, -3a/3b, -4a/4b), and the neuronal and
      inducible isoforms of NO synthase (nNOS and iNOS) in the RVLM of Wistar Kyoto
      (WKY) and spontaneously hypertensive rats (SHR), based on the hypothesis that
      altered NMDA receptor make-up or altered expression of endogenous NO may be
      associated with the increase in sympathetic output described from this site in
      hypertension. Total RNA was extracted and reverse transcribed from the RVLM of
      mature male WKY and SHR (16-23 weeks). Conventional polymerase chain reaction
      (PCR) indicated that only the NR1 splice variants NR1-2a, NR1-2b, NR1-4a and NR1
      4b were expressed in the RVLM of either species. Quantitative real-time PCR
      indicated that for both strains of rat, mRNA for the NR1 subunit (all splice
      variants) was the most abundant (16.5-fold greater, P< or =0.05, relative to the
      NR2A subunit). Amongst the NR2A-D subunits, NR2C was the most abundant (7- and
      1.7-fold greater relative to the NR2A subunit, P< or =0.05, WKY and SHR,
      respectively). Relative to WKY, mRNA levels for the NR2C and NR2D subunits in the
      SHR RVLM were significantly lower (0.3- and 0.25-fold less, P< or =0.05), while
      nNOS was significantly higher (1.76-fold greater, P< or =0.05). This was
      confirmed immunohistochemically for nNOS expression. These results demonstrate
      differential expression levels of NMDA receptor subunits and NOS isoforms in the
      RVLM region of SHR when compared to WKY rats.

PMID- 15469881
TI  - Combined proteomic approach with SELDI-TOF-MS and peptide mass fingerprinting
      identified the rapid increase of monomeric transthyretin in rat cerebrospinal
      fluid after transient focal cerebral ischemia.
AB  - Several proteins are known to be markedly expressed in the brain during cerebral
      ischemia, however the change in protein profiles within the cerebrospinal fluid
      (CSF) after an ischemic insult has not been fully elucidated. We studied the
      changes in the CSF proteome in rat transient middle cerebral artery occlusion
      model. Surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF)
      mass spectrometry (MS) was used to detect the time-course changes in CSF protein
      patterns after transient focal brain ischemia. According to hierarchical cluster
      analysis by self-organising tree algorism (SOTA), the temporal pattern of protein
      peaks was divided into four groups: acute increase group, chronic increase group,
      gradual decrease group and unchanged group. In the acute increase group, the
      expression of a 13.6-kDa protein was markedly increased during the acute phase.
      The 13.6-kDa protein was identified as monomeric form of transthyretin using two
      dimensional electrophoresis and peptide mass fingerprinting based on matrix
      assisted laser desorption/ionization-time of flight mass spectrometry. The
      monomeric transthyretin may represent an ischemia-specific CSF marker to indicate
      the sequential changes according to ischemic insults of the brain.

PMID- 15469882
TI  - Cloning of chicken choline acetyltransferase and its expression in early
      embryonic retina.
AB  - The enzyme choline acetyltransferase [EC 2.3.1.6] (ChAT) synthesizes the
      neurotransmitter acetylcholine that plays a key morphogenic role in vertebrate
      retina development. As the embryonic avian retina is particularly useful for
      morphogenetic studies, we cloned the complete coding region of chicken ChAT cDNA.
      At the deduced amino acid level, chicken ChAT is approximately 76% identical to
      mammalian ChAT proteins. We also report here the cloning of the complete 5' end
      of the complex cholinergic locus. This locus contains both the ChAT gene and the
      nested intronless gene for the vesicular acetylcholine transporter (VAChT). The
      genomic organization of the 5' end of the chicken cholinergic locus is similar to
      that reported in other vertebrate species. A 5.7 kb mRNA corresponding to the
      ChAT message was detected in both embryonic retina and post-hatch brain. An
      analysis of the ChAT mRNA in embryonic chick retina shows that the message can be
      detected by E6 and its level increased during early retinal development.
      Vertebrate ChAT mRNAs can contain one or more of three non-coding exons, M, N or
      R and by RT-PCR we demonstrate, at least, a chicken ChAT mRNA containing exon M.

PMID- 15469883
TI  - In vitro and in vivo effects of an alpha3 neuronal nicotinic acetylcholine
      receptor antisense oligonucleotide.
AB  - In the mammalian central nervous system (CNS), a family of alpha and beta
      subunits (alpha2-7, beta2-4) assemble to form both hetero- and homopentameric
      neuronal nicotinic acetylcholine receptors (nAChRs). In contrast to alpha4beta2
      and alpha7, the predominant brain subtypes, far less is known regarding the
      functional expression and significance of alpha3-containing nAChRs in the CNS. In
      trying to better understand the role alpha3 in the CNS, an antisense knockdown
      strategy was utilized in the present studies. Specifically, Isis 106567 was
      identified out of 80 antisense oligonucleotides (aONs) designed and screened for
      their ability to reduce alpha3 mRNA expression in PC-12 cells. In addition to
      reducing alpha3 mRNA by greater than 75%, Isis 106567 attenuated nicotine-induced
      calcium influx in alpha3-expressing F11 cells. In vivo studies revealed
      significant reduction of alpha3 mRNA levels in both thalamus and medial habenula,
      regions known to express alpha3, following continuous (7 days)
      intracerebroventricular (i.c.v.) infusion of Isis 106567 in rats. Consistent with
      functional alpha3 knockdown, epibatidine-induced c-Fos expression in the medial
      habenula was attenuated in aON-treated rats. Known physiological responses
      elicited by epibatidine, such as hypothermia and micturition, were not affected
      by alpha3 aON treatment. However, the incidence of epibatidine-induced seizures
      was reduced in alpha3-antisense aON-treated rats, suggesting that alpha3 may be
      involved in mediating seizures produced by the nAChR agonist. Results of our
      studies suggest that Isis 106567 may be a useful in vivo tool for characterizing
      the functional significance of alpha3 expression in the CNS.

PMID- 15469884
TI  - A cDNA microarray analysis of gene expression profiles in rat hippocampus
      following a ketogenic diet.
AB  - The ketogenic diet (KD) is an effective therapy for medically intractable
      epilepsy, but its anticonvulsant mechanisms are unknown. Few studies to date have
      addressed the molecular changes following treatment with a KD. In the present
      study, we fed juvenile rats either a standard diet or a KD for 1 month, and then
      determined changes in hippocampal gene expression using cDNA microarray analysis
      (Clontech). To validate the microarray expression results, we also performed
      Northern blot and RT-PCR analysis on a small subset of affected genes. Among a
      total of 1176 cDNAs, 42 genes were strongly up- or down-regulated (>2-fold change
      over controls) by a KD. We found that the expression of mitochondrial ATP
      synthase beta subunit, mitochondrial ATP synthase D subunit (ATP5H) and
      mitochondrial ATP synthase beta subunit precursor (ATP5F) were especially
      increased in KD-treated group, whereas the KD down-regulated protein kinase C
      (PKC) beta and epsilon isoforms. Thus, the most prominent changes were seen in
      genes encoding proteins involved in mitochondrial metabolic and intracellular
      signal transduction pathways. Our data provide some insights into the complex
      cascade of cellular changes in the hippocampus induced by a KD, some of which may
      contribute to its anticonvulsant effects.

PMID- 15469885
TI  - Effects of adenoviral vector-mediated BDNF expression on the bulbectomy-induced
      apoptosis of olfactory receptor neurons.
AB  - The expression of adenoviral vector (Ad)-mediated lacZ and brain-derived
      neurotrophic factor (BDNF) in mouse olfactory epithelium (OE) was examined, and
      the effect of BDNF on the survival of the bulbectomized OE was evaluated. A
      recombinant adenovirus, Ax1CAlacZ, was administrated into the mouse OE after
      bulbectomy, and the expression of a transferred E. coli beta-galactosidase (beta
      gal) gene was confirmed by X-gal staining. The expression and effects of
      exogenous BDNF in the OE after bulbectomy were examined using
      immunohistochemistry and the TUNEL method. The adenoviral vector-mediated
      expression of beta-gal in the mouse OE was detectable for up to 14 days after
      bulbectomy in vivo. The Ad-mediated expression of BDNF was also observed in the
      OE after bulbectomy. Exogenously induced BDNF suppressed the degenerative changes
      of bulbectomized OE. TUNEL staining indicated that the exogenous BDNF enhanced
      the survival of the bulbectomized OE by inhibiting apoptosis. Ad-mediated
      expression of BDNF in the mouse nasal mucosa alleviated degenerative changes in
      bulbectomized OE. Ad-mediated transfer of neurotrophic factors might be
      applicable in the treatment of olfactory disorders.

PMID- 15469886
TI  - Ischemic preconditioning-induced expression of gp130 and STAT3 in astrocytes of
      the rat hippocampus.
AB  - We investigated the distribution and time course of expression of both gp130 mRNA
      and signal transducer and activator of transcription factor-3 (STAT3) in a rat
      model of ischemic tolerance induction. Forebrain ischemia was induced by four
      vessel occlusion for 3 min as an ischemic preconditioning. Ischemic
      preconditioning 3 days before a 10-min lethal ischemia preserved neuronal signal.
      Expression of gp130 mRNA was induced 12 h after ischemic preconditioning, and was
      most prominent in the CA1 and the hilar region at 3 days, with expression
      sustained for at least 7 days. Ischemic preconditioning-induced STAT3 activation,
      as revealed by nuclear translocation, resembled that of gp130 expression. Nuclear
      STAT3 immunoreactivity occurred in the CA1 and the hilar region within 12 h after
      ischemic preconditioning, and was sustained for at least 7 days. Double-labeling
      experiments revealed that the cells expressing gp130 or STAT3 were glial
      fibrillary acidic protein (GFAP) immunoreactive astrocytes. These results
      demonstrate upregulation of gp130 and STAT3 in reactive astrocytes following
      ischemic preconditioning, indicating that this signal pathway is involved in the
      astroglial reaction to ischemic preconditioning in the rat hippocampus.

PMID- 15469887
TI  - Reduced anxiety-related behaviour in transgenic mice overexpressing serotonin 1A
      receptors.
AB  - Serotonergic neurons play a major role in the modulation of emotion and
      behaviour. Especially knockout studies have revealed a role for the serotonin(1A)
      (5-HT(1A)) receptor in anxiety related behaviour. Mutant animals exhibit enhanced
      anxiety-like responses, possibly resulting from impaired autoinhibitory control
      of midbrain serotonergic neurons. To further elucidate the role of the 5-HT(1A)
      receptors in affective behaviour, a complementary approach has been used and
      transgenic mice overexpressing this receptor subtype have been generated. The
      expression of the active 5-HT(1A) receptor protein as indicated by
      autoradiography was transiently increased during early postnatal development
      (P1.5) as compared to wild-type mice. Within the next 2 weeks, the increase in
      receptor binding vanished and was also not apparent in adult animals indicating
      adaptive changes in the regulation of 5-HT(1A) receptor expression. Although no
      evidence for increased receptor binding in the brains of adult homozygous mice
      was found by autoradiography, typical phenotypic changes indicative of 5-HT(1A)
      receptor overactivity were apparent. Transgenic mice revealed a reduced molar
      ratio of 5-hydroxyindoleacetic acid to serotonin in several brain areas and
      elevated serotonin values in the hippocampus and striatum. Moreover, anxiety-like
      behaviour was decreased in male and female transgenic mice and body temperature
      was lowered in male transgenic mice in comparison with heterozygous and wild-type
      mice. These findings further underline the pivotal role of 5-HT(1A) receptors in
      the homeostasis of anxiety-like behaviour and the crucial importance of
      stimulation of the 5-HT(1A) receptor during the early postnatal development for
      normal anxiety-like behaviour throughout life.

PMID- 15469888
TI  - Effect of genetic polymorphism on the metabolism of endogenous neuroactive
      substances, progesterone and p-tyramine, catalyzed by CYP2D6.
AB  - Metabolic activities toward endogenous substrates in the brain, progesterone and
      p-tyramine, by cytochrome P450 2D6.2 (CYP2D6.2), CYP2D6.10A, CYP2D6.10C, and
      P34S, G42R, R296C, and S486T mutants expressed in recombinant Saccharomyces
      cerevisiae were compared with those by CYP2D6.1 (wild-type) in order to clarify
      the effects of genetic polymorphism of CYP2D6 on the metabolism of neuroactive
      steroids and amines in the brain. For the 6beta-hydroxylation of progesterone,
      the V(max) values for CYP2D6.2, CYP2D6.10A, and the P34S and G42R mutants, were
      less than half of those for CYP2D6.1, and CYP2D6.10C had a higher K(m) and a
      lower V(max) than the wild-type. The V(max)/K(m) values for CYP2D6.10A,
      CYP2D6.10C, and the P34S and G42R mutants were 12-31% of that for CYP2D6. The
      16alpha-hydroxylation and 21-hydroxylation of progesterone by CYP2D6.10A,
      CYP2D6.10C, and the P34S and G42R mutants were not detected, and the R296C mutant
      had a higher K(m) for the 16alpha-hydroxylation and a lower V(max) for the 21
      hydroxylation than those for CYP2D6.1. For dopamine formation from p-tyramine,
      the K(m) values for CYP2D6.2 and the R296C mutant were higher than those for
      CYP2D6.1, CYP2D6.10A, and CYP2D6.10C had a higher K(m) and a lower V(max) than
      the wild-type. The V(max)/K(m) values for CYP2D6.2, CYP2D6.10A, CYP2D6.10C and
      the P34S, G42R and R296C mutants were less than 45% of those for the wild-type.
      These results suggest the possibility that the polymorphism of CYP2D6, including
      CYP2D6*2, CYP2D6*10 and CYP2D6*12, might affect an individual behavior and the
      central nervous system through endogenous compounds, such as neuroactive steroids
      and tyramine, in the brain.

PMID- 15469890
TI  - Gene expression profiles highlight adaptive brain mechanisms in corticotropin
      releasing factor overexpressing mice.
AB  - Corticotropin-releasing factor (CRF) plays an important role in mediating central
      and peripheral responses to stress. Alterations in CRF system activity have been
      linked to a number of psychiatric disorders, including anxiety and depression.
      Aim of this study was to elucidate homeostatic mechanisms induced by lifelong
      elevated CRF levels in the brain. We therefore profiled gene expression in
      several brain areas of transgenic mice overexpressing CRF (CRF-OE), a model for
      chronic stress. Several genes showed altered expression levels in CRF-OE mice
      when compared to their wild type littermates and were confirmed by quantitative
      PCR. Differences in gene expression profiles revealed the presence of previously
      unrecognized homeostatic mechanisms in CRF-OE animals. These included changes in
      glucocorticoid signaling, as exemplified by changes in 11beta-hydroxysteroid
      dehydrogenase type 1, FK506 binding protein 5 and serum/glucocorticoid kinase.
      Alterations in expression of genes involved in myelination (myelin, myelin
      associated glycoprotein), cell proliferation and extracellular matrix formation
      (Edg2, Fgfr2, decorin, brevican) suggest changes in the dynamics of neurogenesis
      in CRF-OE. Pronounced changes in neurotensin (NT) receptors 1 and 2 mRNA were
      identified. Overall downregulation of NT receptors in CRF-OE animal was
      substantiated by receptor binding studies. Pronounced neurotensin receptor
      downregulation was observed for NT type 1 receptors in limbic brain areas,
      suggesting that NT could be implicated in some of the effects attributed to CRF
      overexpression. These data show that lifelong exposure to excessive CRF leads to
      adaptive changes in the brain which could play a role in some of the behavioral
      and physiological alterations seen in these animals.

PMID- 15469889
TI  - Altered expression of Bcl2, Bad and Bax mRNA occurs in the rat cerebellum within
      hours after ethanol exposure on postnatal day 4 but not on postnatal day 9.
AB  - Previous studies have demonstrated that ethanol exposure during the vulnerable
      postnatal (PN) day 4-6 period results in a dose-dependent loss of Purkinje
      neurons in rats by apoptosis. Although the mechanism of ethanol action and the
      reasons for Purkinje cell vulnerability are unknown, we hypothesize that during
      the PN4-6 vulnerable period Purkinje cells are dependent on active trophic factor
      suppression of apoptosis. Furthermore, ethanol acts to prevent the reception of
      this trophic signaling resulting in the execution of the apoptotic pathway that
      includes specific alterations of proteins in the Bcl2 gene family. Ethanol
      exposure that occurs after this vulnerable period (i.e. PN9) would not be
      expected to demonstrate alterations in these apoptotic proteins since the
      Purkinje cells no longer demonstrate vulnerability to ethanol. The current study
      was undertaken to identify the alterations in mRNA expression for members of the
      Bcl2-family within the initial hours following ethanol administration on PN4 or
      PN9. Semi-quantitative reverse transcriptase with polymerase chain reaction (PCR)
      techniques were used to determine the expression levels of pro-apoptotic factors
      Bad and Bax, and anti-apoptotic Bcl(2) mRNA. Ethanol was administered at four
      different doses (1.5, 3.0, 4.5, and 6.0 g/kg) on PN4 and analyses of whole
      cerebellar mRNA was conducted at 1, 4, 6, and 8 h after treatment. Doses greater
      than 1.5 g/kg produced significant decreases in Bcl(2) and significant increases
      in Bad and Bax mRNA during the 8-h period after treatment. In stark contrast,
      when ethanol was administered at 3.0 or 6.0 g/kg to PN9 pups, no significant
      alterations of these apoptotic factors were identified at either 1 or 4 h after
      treatment. These results are in agreement with and provide further support for
      our hypothesis that ethanol interrupts the active suppression of apoptosis that
      is a crucial feature of Purkinje cell vulnerability during this time period.

PMID- 15469891
TI  - Transcription of SCO-spondin in the subcommissural organ: evidence for down
      regulation mediated by serotonin.
AB  - The subcommissural organ (SCO) is a brain gland located in the roof of the third
      ventricle that releases glycoproteins into the cerebrospinal fluid, where they
      form a structure known as Reissner's fiber (RF). On the basis of SCO-spondin
      sequence (the major RF glycoprotein) and experimental findings, the SCO has been
      implicated in central nervous system development; however, its function(s) after
      birth remain unclear. There is evidence suggesting that SCO activity in adult
      animals may be regulated by serotonin (5HT). The use of an anti-5HT serum showed
      that the bovine SCO is heterogeneously innervated with most part being poorly
      innervated, whereas the rat SCO is richly innervated throughout. Antibodies
      against serotonin receptor subtype 2A rendered a strong immunoreaction at the
      ventricular cell pole of the bovine SCO cells and revealed the expected
      polypeptides in blots of fresh and organ-cultured bovine SCO. Analyses of organ
      cultured bovine SCO treated with 5HT revealed a twofold decrease of both SCO
      spondin mRNA level and immunoreactive RF glycoproteins, whereas no effect on
      release of RF glycoproteins into the culture medium was detected. Rats subjected
      to pharmacological depletion of 5HT exhibited an SCO-spondin mRNA level twofold
      higher than untreated rats. These results indicate that 5HT down-regulates SCO
      spondin biosynthesis but apparently not its release, and suggest that 5HT may
      exert the effect on the SCO via the cerebrospinal fluid.

PMID- 15469892
TI  - Regulation of microtubule-associated proteins, protein kinases and protein
      phosphatases during differentiation of SY5Y cells.
AB  - Regulation of expression and function of microtubule-associated proteins (MAPs)
      is critical for neurons to maintain normal cytoskeletal architecture and
      functions. We have shown previously that in differentiated human neuroblastoma
      SY5Y cells, the expression of tau, a major neuronal MAP, is dramatically
      increased, and tau phosphorylation is differentially regulated. In the present
      study, we investigated the expression, the subcellular distribution and the
      microtubule-binding activities of several MAPs in SY5Y cells upon
      differentiation. We also studied the activities of protein kinases and
      phosphatases that are involved in regulation of tau phosphorylation during cell
      differentiation. We found that the expression of MAP1b in addition to tau was
      upregulated upon differentiation. Tau, MAP1a, MAP1b and MAP2 had distinct
      immunocytochemical staining patterns in differentiated SY5Y cells, suggesting
      differential biological functions. The microtubule-binding activity of tau
      increased after cell differentiation, whereas the activities of MAP1a and MAP2
      decreased. Upon differentiation, the phosphorylation of tau at
      Ser198/Ser199/Ser202 and Ser396/Ser404 was increased, but that at Ser262/Ser356
      was decreased. These changes in tau phosphorylation were accompanied by an
      upregulation of activities of several protein kinases (cdk5, MAPK, PKC and CK-1)
      as well as protein phosphatases PP-1 and PP-2A. These results suggest that the
      expression, post-translational modifications and biological activities of various
      MAPs are differentially regulated to meet the biological needs during cell
      differentiation.

PMID- 15469893
TI  - Neurogranin expression in stably transfected N2A cell line affects cytosolic
      calcium level by nitric oxide stimulation.
AB  - To test a cellular effect of rodent neurogranin (Ng) oxidation as compared to Ng
      phosphorylation, we develop a cell model capable of stable expression of Ng using
      the Tet-On system, and determine whether Ng oxidation regulates intracellular
      calcium level. Our results show that Ng oxidation by nitric oxide donor induces
      an increase of [Ca(2+)](i) in Ng-expressed cells as compared to the control cells
      without expressing Ng. These results suggest that Ng oxidation plays a
      significant role in intracellular Ca(2+) homeostasis, essential for the activated
      signaling networks in learning and memory.

PMID- 15469894
TI  - Brainstem prolactin mRNA is enhanced in mice with suppressed neuronal nitric
      oxide synthase activity.
AB  - Prolactin (PRL) and vasoactive intestinal polypeptide (VIP) mRNA levels were
      elevated in the brainstem of neuronal nitric oxide synthase (nNOS) gene knockout
      (KO) mice compared to the levels in nNOS control mice. In addition, PRL mRNA
      levels increased in the hypothalamus and the brainstem of nNOS control mice after
      administration of 7-nitro-indazole (7-NI), a relatively selective nNOS inhibitor.
      The results suggest that NO inhibits PRL. No differences in the genes measured
      were observed in inducible NOS KO mice.

PMID- 15469895
TI  - Regulation of growth factor receptor bound 2 by electroconvulsive seizure.
AB  - Electroconvulsive seizure (ECS) is a well-established non-chemical antidepressant
      that is effective in the treatment of severe depression and also in subjects
      resistant to chemical antidepressant treatment. Although the molecular mechanism
      governing the antidepressant efficacy of ECS is unknown, recent work suggests
      that an amplification of growth/neurotrophic signaling might play a role in
      mediating the therapeutic effects. In this context, we examined the regulation of
      growth factor receptor bound 2 (Grb2), an important adaptor molecule in several
      growth factor signaling cascades. In situ hybridization analysis revealed a more
      than 2-fold induction of Grb2 mRNA in the hippocampal dentate gyrus as well as
      superficial and deep layers of the cortex with both acute and chronic ECS. Grb2
      also exhibited a time-dependent induction 4 and 8 h after acute ECS, returning to
      basal levels at 24 h. These results provide further evidence of increased growth
      factor signaling in response to ECS.

PMID- 15469896
TI  - Differential regulation of variant glucocorticoid receptor mRNAs in the rat
      hippocampus by the antidepressant fluoxetine.
AB  - Adult rats were given antidepressant drugs orally. Fluoxetine, but not
      moclobemide, venlafaxine, tianeptine or desipramine, increased total
      glucocorticoid receptor (GR) mRNA in the hippocampus after 4 weeks. Further
      examination revealed that GR mRNA containing the brain-specific exon 1(7) was
      increased across all hippocampal subregions. In contrast, expression of the major
      exon 1(10) and another brain-specific exon 1(5)-containing GR mRNAs were
      unchanged. Tissue-specific first exon usage may contribute to the differential
      regulation of GR by fluoxetine in brain subregions.

PMID- 15469897
TI  - Exploration of neuroendocrine and immune gene expression in peripheral blood
      mononuclear cells.
AB  - As pathways of communication between the nervous, endocrine, and immune systems
      are identified, the importance of the interplay of these systems for health and
      well-being is increasingly recognized. In this study, we created a comprehensive
      database of 1622 genes likely to be involved in synthetic, biochemical, and
      regulatory psycho-neuroendocrine-immune (PNI) pathways. Expression of 1058 of
      these genes was detected in the peripheral blood by querying both a peripheral
      blood-specific expressed sequence tag (EST) database and a peripheral blood
      database generated from microarray evaluation of 30,000 genes. Several neural and
      endocrine genes were expressed in the peripheral blood including hormone
      receptors, a hormone-responsive transcription factor, and neurotransmitter
      receptors. These findings document the expression of nervous and endocrine genes
      in the peripheral blood that have previously only been characterized in the
      respective system tissues, and indicate that the blood is a rich source of
      information that should help in deciphering the communication between the mind
      and the body.

PMID- 15469898
TI  - Lipopolysaccharides of Vibrio cholerae II. Genetics of biosynthesis.
AB  - An account of our up to date knowledge of the genetics of biosynthesis of Vibrio
      cholerae lipopolysaccharide (LPS) is presented in this review. While not much
      information is available in the literature on the genetics of biosynthesis of
      lipid A of V. cholerae, the available information on the characteristics and
      proposed functions of the corepolysaccharide (core-PS) biosynthetic genes is
      discussed. The genetic organizations encoding the O-antigen polysaccharides (O
      PS) of V. cholerae of serogroups O1 and O139, the disease causing ones, have been
      described along with the putative functions of the different constituent genes.
      The O-PS biosynthetic genes of some non-O1, non-O139 serogroups, particularly the
      serogroups O37 and O22, and their putative functions have also been discussed
      briefly. In view of the importance of the serogroup O139, the origination of the
      O139 strain and the possible donor of the corresponding O-PS gene cluster have
      been analyzed with a view to having knowledge of (i) the mode of evolution of
      different serogroups and (ii) the possible emergence of pathogenic strain(s)
      belonging to non-O1, non-O139 serogroups. The unsolved problems in this area of
      research and their probable impact on the production of an effective cholera
      vaccine have been outlined in conclusion.

PMID- 15469899
TI  - Functional analysis of altered reduced folate carrier sequence changes identified
      in osteosarcomas.
AB  - Osteosarcomas are common primary malignant bone tumors that do not respond to
      conventional low-dose treatments of methotrexate (Mtx), suggesting an intrinsic
      resistance to this drug. Previous work has shown that cDNAs generated from
      osteosarcoma mRNA from a fraction of patients contain sequence changes in the
      reduced folate carrier (RFC), the membrane protein transporter for Mtx. In this
      study, the functionality of the altered RFC proteins was assessed by fusing the
      green fluorescent protein (GFP) to the C-terminal, and examining the ability of
      the transfected constructs to complement a hamster cell line null for the
      carrier. Confocal microscopy and cell surface biotinylation indicated that all
      altered proteins were properly localized at the cell membrane. Only one of those
      examined, Leu291Pro, was unable to complement the null carrier line, but did bind
      Mtx at the cell surface. Thus, this alteration confers drug resistance since the
      carrier is unable to translocate the substrate across the cell membrane. Three
      alterations, Ser46Asn, Ser4Pro and Gly259Trp, while able to complement the
      carrier null line, conferred some degree of resistance to Mtx via a decreased
      rate of transport (Vmax). Another set of alterations, Glu21Lys, Ala7Val, and the
      combined changes Thr222Ile, Met254Thr, complemented the carrier null line and did
      not confer resistance to Mtx. Thus, some, but not all of these identified
      alterations in the RFC may contribute to the lack of responsiveness of
      osteosarcomas to Mtx treatment.

PMID- 15469900
TI  - Role of bicarbonate/CO2 buffer in the initiation of vesicle-mediated
      calcification: mechanisms of aortic calcification related to atherosclerosis.
AB  - Calcifying vesicles play an important role in the mechanism of aortic
      calcification induced by dietary cholesterol interventions. This study was
      initiated to test the hypothesis that alterations in the ratio of
      bicarbonate/CO2, which is a main physiological buffer, could affect vesicle
      mediated calcification. Using rabbits as a model, in vitro calcification of
      vesicles isolated from aortas was performed to study the effect of the
      bicarbonate buffer on the mineralization process. When Tris buffer was initially
      used to maintain pH of the media, ATP-dependent vesicle calcification increased
      with pH of calcifying media. By replacing Tris with physiological bicarbonate/CO2
      buffer, ATP-dependent vesicle calcification increased rapidly with increased
      ratios of bicarbonate/CO2. The increase appears to be a result of elevated levels
      of pH through the alteration in the ratios of bicarbonate/CO2. The effect of the
      physiological concentration of bicarbonate (30 mM) on pH of calcifying media was
      remarkable since 50 mM of Tris buffer at pH 7.6 failed to prevent a rapid rise in
      pH under atmospheric CO2. The effect of bicarbonate and CO2 on vesicle
      calcification was dependent on the ratio of the surface area to the volume of
      calcifying media, since the ratio profoundly affects the exchange rate between
      the gas and liquid phases of CO2. Although the pathological conditions that alter
      the pH remain unknown, it is conceivable that blockage in the supply of blood CO2
      to the media by intimal thickening in the lesions could contribute to focal
      calcification. We conclude that bicarbonate buffer could provide a dynamic and
      rapid transitional increase in pH of extracellular fluids, thereby creating a
      favorable condition for the initiation of vesicle-mediated calcification under
      pathological conditions.

PMID- 15469901
TI  - The transferrin homologue, melanotransferrin (p97), is rapidly catabolized by the
      liver of the rat and does not effectively donate iron to the brain.
AB  - Melanotransferrin (MTf) or melanoma tumor antigen p97 is a membrane-bound
      transferrin (Tf) homologue that binds iron (Fe). This protein is also found as a
      soluble form in the plasma (sMTf) and was suggested to be an Alzheimer's disease
      marker. In addition, sMTf has been recently suggested to cross the blood-brain
      barrier (BBB) and accumulate in the brain of the mouse following intravenous
      infusion. Considering the importance of this observation to the physiology and
      pathophysiology of the BBB and the function of sMTf in vivo, we investigated the
      uptake and distribution of 59Fe-125I-sMTf and compared it to 59Fe-125I-Tf that
      were injected intravenously in rats. Studies were also performed to measure 59Fe
      and 125I-protein uptake by reticulocytes using these radiolabelled proteins. The
      results showed that sMTf was rapidly catabolized, mainly in the liver and to a
      lesser extent by the kidneys. The 59Fe was largely retained by these organs but
      the 125I was released into the plasma. Only a small amount of 125I-sMTf or its
      bound 59Fe was taken up by the brain, less than that from 59Fe-125I-Tf. There was
      much less 59Fe uptake by erythropoietic organs (spleen and femurs) from 59Fe-sMTf
      than from 59Fe-Tf, and no evidence of receptor-mediated uptake of sMTf was
      obtained using reticulocytes. It is concluded that compared to Tf, sMTf plays
      little or no role in Fe supply to the brain and erythropoietic tissue. However, a
      small amount of sMTf was taken up from the plasma by the brain and a far greater
      amount by the liver.

PMID- 15469902
TI  - Two novel mutations of Wiskott-Aldrich syndrome: the molecular prediction of
      interaction between the mutated WASP L101P with WASP-interacting protein by
      molecular modeling.
AB  - Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by eczema,
      thrombocytopenia and increased susceptibility of infections, with mutations of
      the WAS gene being responsible for WAS and X-linked thrombocytopenia. Herein, two
      novel mutations of WAS at T336C on exon 3, and at 1326-1329, a G deletion on exon
      10, resulting in L101P missense mutation and frameshift mutation 444 stop,
      respectively, are reported. The affected patients with either mutation showed
      severe suppression of WAS protein (WASP) levels, T cell proliferation, and CFSE
      labeled T cells division. Because WASP L101 have not shown direct nuclear
      Overhauser effect (NOE) contact with the WASP-interacting protein (WIP) in NMR
      spectroscopy, molecular modeling was performed to evaluate the molecular effect
      of WASP P101 to WIP peptide. It is presumed that P101 induced a conformational
      change in the Q99 residue of WASP and made the side chain of Q99 move away from
      the WIP peptide, resulting in disruption of the hydrogen bond between Q99 WASP
      and Y475 WIP. A possible model for the molecular pathogenesis of WAS has been
      proposed by analyzing the interactions of WASP and WIP using a molecular modeling
      study.

PMID- 15469903
TI  - Purification, characterisation and intracellular localisation of aryl hydrocarbon
      interacting protein-like 1 (AIPL1) and effects of mutations associated with
      inherited retinal dystrophies.
AB  - Mutations in AIPL1 are associated with Leber Congenital Amaurosis (LCA), a major
      cause of childhood blindness, yet the cellular function of the encoded protein
      has yet to be fully elucidated. In order to investigate the biochemistry of
      AIPL1, we have developed a system for the expression of the recombinant protein
      in bacteria and its subsequent purification. The secondary structure and
      thermostability of wild-type and mutant proteins have been examined by circular
      dichroism (CD) spectroscopy. Some of the variants, notably W278X and P376S, had
      markedly different secondary structure compositions, indicating that the proteins
      had not folded properly, whilst W278X and T114I were particularly thermolabile.
      When eukaryotic cells were transfected with the AIPL1 expression constructs, we
      show by immunofluorescence microscopy that wild-type protein is distributed
      throughout the nucleus and cytoplasm. Several of the mutants give similar
      results. With two of the disease-associated variants (W278X and A336Delta2),
      however, the protein remains in the cytoplasm in aggresome-like particles. These
      particles were shown to be ubiquitinated, indicating that the mutant protein had
      been tagged for proteosomal degradation. On this basis, we can conclude that wild
      type protein is expressed in a soluble and folded manner, and that some of the
      disease-associated mutant proteins are nonfunctional because they are insoluble
      and are degraded by the cell. Other mutations appear to have a more localised
      effect on secondary structure, which does not result in insolubility or affect
      protein targeting, but reduces the stability of the protein at human body
      temperature.

PMID- 15469904
TI  - Role of ceramide in activation of stress-associated MAP kinases by minimally
      modified LDL in vascular smooth muscle cells.
AB  - Interaction of oxidized low-density lipoprotein (LDL) with arterial smooth muscle
      cells (SMC) is believed to play a key role in the development of atherosclerosis.
      Depending on the extent of oxidation, apolipoproteins and/or lipids in the
      particle may be modified and thus lead to different cellular responses (e.g.
      proliferation or cell death). Here we report on the signaling effects of LDL, in
      which only the lipids were oxidized. This so-called minimally modified LDL
      (mmLDL) mainly activated components involved in stress response and apoptotic
      cell death including p38 mitogen-activated protein kinase (MAPK) and c-Jun N
      terminal kinase/stress-activated protein kinase (JNK) as well as neutral and acid
      sphingomyelinase. In contrast, proliferative signaling elements such as
      extracellular regulated kinase, AKT-kinase and phospho-BAD seem to play a minor
      role as they were only slightly stimulated by mmLDL. Ceramide, the hydrolysis
      product of sphingomyelin, seems to be a key mediator as it mimics mmLDL by
      inducing activation of the same signaling components. Moreover, mmLDL- and
      ceramide-associated effects on apoptotic protein kinases were abolished by NB6, a
      specific inhibitor of acid sphingomyelinase. Thus, acid sphingomyelinase is very
      likely to be primarily responsible for triggering intracellular signal
      transduction in SMC after exposure to mmLDL via formation of ceramide by an
      autocatalytic mechanism.

PMID- 15469905
TI  - Characterization of the peroxidase system at low H2O2 concentrations in isolated
      neonatal rat islets.
AB  - B cell destruction during the onset of diabetes mellitus is associated with
      oxidative stress. In this work, we attempted to further trace the fate of H2O2
      inside the pancreatic islets and determine whether it is mediated by enzymatic
      (peroxidase) activity or by chemical reaction with thiols from any protein chain.
      Our results suggest that the islet cells have a very similar peroxidase activity
      at the hydrophilic (cytoplasm) and hydrophobic compartments (organelles and
      nucleus), independent of the catalase content of the samples. This activity is
      composed of sacrificial thiols and by proteins with Fe3+/Mn3+ ions at non-heme
      catalytic sites. The capacity of the hydrophobic fraction to scavenge O2- was
      increased in the presence of high concentrations of NADP* and RS* and was highly
      dependent on RSH. On the contrary, the hydrophilic fraction exhibited a low RSH
      dependent activity where the O2- scavenging is related to metal Cu2+/Fe3+/Mn3+
      ions attached to the protein molecules.

PMID- 15469906
TI  - Tissue-specific changes in iron metabolism genes in mice following
      phenylhydrazine-induced haemolysis.
AB  - Iron metabolism in animals is altered by haemolytic anaemia induced by
      phenylhydrazine (PHZ). In common with a number of other modulators of iron
      metabolism, the mode and the mechanisms of this response are yet to be
      determined. However, recent studies have shown increased expression of the
      ferrous transporter DMT1 in the duodenum and other tissues of mice administered
      PHZ. We examined the expression of the ferric reductase Dcytb, DMT1 and some
      other genes involved in Fe metabolism in tissues of mice dosed with PHZ. The
      expression of iron-related genes in the duodenum, liver, and spleen of the mice
      were evaluated using Northern blot analyses, RT-PCR and immunocytochemistry.
      Dcytb, and DMT1 mRNA and protein increased markedly in the duodenum of mice given
      PHZ. The efflux protein Ireg1 also increased in the duodenum of the treated mice.
      These changes correlated with a decrease in hepatic hepcidin expression. Dcytb,
      DMT1, Ireg1 and transferrin receptor 1 mRNA expression in the spleen and liver of
      mice treated with PHZ responded to the enhanced iron demand associated with the
      resulting stimulation of erythropoiesis. Enhanced iron absorption observed in PHZ
      treated animals is facilitated by the up-regulation of the genes involved in iron
      transport and recycling. The probable association of the erythroid and the store
      regulators of iron homeostasis and absorption in the mice is discussed.

PMID- 15469907
TI  - Modification of myosin protein and gene expression in failing hearts due to
      myocardial infarction by enalapril or losartan.
AB  - The effects of enalapril, an angiotensin converting enzyme (ACE) inhibitor, and
      losartan, an angiotensin II receptor type I antagonist, were investigated on
      alterations in myofibrillar ATPase activity as well as myosin heavy chain (MHC)
      content and gene expression in failing hearts following myocardial infarction
      (MI). Three weeks after ligation of the left coronary artery, rats were treated
      with or without enalapril (10 mg/kg/day), and/or losartan (20 mg/kg/day) for 5
      weeks. The infarcted animals exhibited an increase in left ventricle (LV) end
      diastolic pressure and depressed rates of LV pressure development as well as
      pressure decay. LV myofibrillar Ca2+ -stimulated ATPase activity was decreased in
      the infarcted hearts compared with controls, MHC alpha-isoform content was
      significantly decreased whereas that of MHC beta-isoform was markedly increased.
      The level of MHC alpha-isoform mRNA was decreased whereas that of MHC beta
      isoform was increased in the viable infarcted LV. Treatment of animal with
      enalapril, losartan, or combination of enalapril and losartan partially prevented
      the MI induced changes in LV function, myofibrillar Ca2+ -stimulated ATPase
      activity, MHC protein expression and MHC gene expression. The results suggest
      that the beneficial effects of the renin-angiotensin system blockade in heart
      failure are associated with partial prevention of myofibrillar remodeling.

PMID- 15469908
TI  - Position- and orientation-specific enhancement of topoisomerase I cleavage
      complexes by triplex DNA structures.
AB  - Topoisomerase I (Top1) activities are sensitive to various endogenous base
      modifications, and anticancer drugs including the natural alkaloid camptothecin.
      Here, we show that triple helix-forming oligonucleotides (TFOs) can enhance Top1
      mediated DNA cleavage by affecting either or both the nicking and the closing
      activities of Top1 depending on the position and the orientation of the triplex
      DNA structure relative to the Top1 site. TFO binding 1 bp downstream from the
      Top1 site enhances cleavage by inhibiting religation and to a lesser extent DNA
      nicking. In contrast, TFO binding 4 bp downstream from the Top1 site enhances DNA
      nicking especially when the 3' end of the TFO is proximal to the Top1 site.
      However, when the orientation of the triplex is inverted, with its 5' terminus 4
      bp downstream from the Top1 site, religation is also inhibited. These position-
      and orientation-dependent effects of triplex structures on the Top1-mediated DNA
      cleavage and religation are discussed in the context of molecular modeling and
      effects of TFO on DNA twist and mobility at the duplex/triplex junction.

PMID- 15469910
TI  - Targeting a binding pocket within the trimer-of-hairpins: small-molecule
      inhibition of viral fusion.
AB  - Trimeric class I virus fusion proteins undergo a series of conformational
      rearrangements that leads to the association of C- and N-terminal heptad repeat
      domains in a "trimer-of-hairpins" structure, facilitating the apposition of viral
      and cellular membranes during fusion. This final fusion hairpin structure is
      sustained by protein-protein interactions, associations thought initially to be
      refractory to small-molecule inhibition because of the large surface area
      involved. By using a photoaffinity analog of a potent respiratory syncytial virus
      fusion inhibitor, we directly probed the interaction of the inhibitor with its
      fusion protein target. Studies have shown that these inhibitors bind within a
      hydrophobic cavity formed on the surface of the N-terminal heptad-repeat trimer.
      In the fusogenic state, this pocket is occupied by key amino acid residues from
      the C-terminal heptad repeat that stabilize the trimer-of-hairpins structure. The
      results indicate that a low-molecular-weight fusion inhibitor can interfere with
      the formation or consolidation of key structures within the hairpin moiety that
      are essential for membrane fusion. Because analogous cavities are present in many
      class I viruses, including HIV, these results demonstrate the feasibility of this
      approach as a strategy for drug discovery.

PMID- 15469911
TI  - Ammonia-oxidizing bacteria respond to multifactorial global change.
AB  - Recent studies have demonstrated that multiple co-occurring global changes can
      alter the abundance, diversity, and productivity of plant communities. Below
      ground processes, often mediated by soil microorganisms, are central to the
      response of these communities to global change. Very little is known, however,
      about the effects of multiple global changes on microbial communities. We
      examined the response of ammonia-oxidizing bacteria (AOB), microorganisms that
      mediate the transformation of ammonium into nitrite, to simultaneous increases in
      atmospheric CO2, precipitation, temperature, and nitrogen deposition, manipulated
      on the ecosystem level in a California grassland. Both the community structure
      and abundance of AOB responded to these simulated global changes. Increased
      nitrogen deposition significantly altered the structure of the ammonia-oxidizing
      community, consistently shifting the community toward dominance by bacteria most
      closely related to Nitrosospira sp. 2. This shift was most pronounced when
      temperature and precipitation were not increased. Total abundance of AOB
      significantly decreased in response to increased atmospheric CO2. This decrease
      was most pronounced when precipitation was also increased. Shifts in community
      composition were associated with increases in nitrification, but changes in
      abundance were not. These results demonstrate that microbial communities can be
      consistently altered by global changes and that these changes can have
      implications for ecosystem function.

PMID- 15469912
TI  - The Caenorhabditis elegans IMPAS gene, imp-2, is essential for development and is
      functionally distinct from related presenilins.
AB  - Presenilins (PSs) are required for Notch signaling in the development of
      vertebrates and invertebrates. Mutations in human PS1 and PS2 homologs are a
      cause of familial Alzheimer's disease (AD). The function of the recently
      identified ancient family of IMPAS proteins (IMP/SPP/PSH) homologous to PSs is
      not yet known. We show here that, unlike PSs, IMPs (orthologous C. elegans Ce-imp
      2 and human hIMP1/SPP) do not promote Notch (C. elegans lin-12,glp-1) proteolysis
      or signaling. The knock-down of Ce-imp-2 leads to embryonic death and an abnormal
      molting phenotype in Caenorhabditis elegans. The molting defect induced by Ce-imp
      2 deficiency was mimicked by depleting cholesterol or disrupting Ce-lrp-1 and
      suppressed, in part, by expression of the Ce-lrp-1 derivate. C. elegans lrp-1 is
      a homolog of mammalian megalin, lipoprotein receptor-related protein (LRP)
      receptors essential for cholesterol and lipoprotein endocytosis and signaling.
      These data suggest that IMPs are functionally distinct from related PSs and
      implicate IMPs as critical regulators of development that may potentially
      interact with the lipid-lipoprotein receptor-mediated pathway.

PMID- 15469913
TI  - RNA polymerase can track a DNA groove during promoter search.
AB  - Many proteins select special DNA sequences to form functional complexes. In one
      possible mechanism, protein molecules would scan DNA sequences by tracking a
      groove without complete dissociation. Upon dragging single molecules of DNA over
      a surface carrying fixed Escherichia coli RNA polymerase holoenzyme, we detected
      rotation of individual DNA molecules, providing direct evidence that a DNA
      binding protein can track a DNA groove. These results confirm our previous
      observations of longitudinal movement of RNA polymerase along fixed, extended DNA
      and, moreover, imply that groove tracking facilitates scanning of DNA sequences.

PMID- 15469914
TI  - Experimental test of Hatano and Sasa's nonequilibrium steady-state equality.
AB  - Most natural processes occur far from equilibrium and cannot be treated within
      the framework of classical thermodynamics. In 1998, Oono and Paniconi [Oono, Y. &
      Paniconi, M. (1998) Prog. Theor. Phys. Suppl. 130, 29-44] proposed a general
      phenomenological framework, steady-state thermodynamics, encompassing
      nonequilibrium steady states and transitions between such states. In 2001, Hatano
      and Sasa [Hatano, T. & Sasa, S. (2001) Phys. Rev. Lett. 86, 3463-3466] derived a
      testable prediction of this theory. Specifically, they were able to show that the
      exponential average of Y, a quantity similar to a dissipated work, should be
      equal to zero for arbitrary transitions between nonequilibrium steady states, 
      ln<e(-Y)> = 0. We have tested this strong prediction by measuring the dissipation
      and fluctuations of microspheres optically driven through water. We have found
      that -ln<e(-Y)> approximately 0 for three different nonequilibrium systems,
      supporting Hatano and Sasa's proposed extension of thermodynamics to arbitrary
      steady states and irreversible transitions.

PMID- 15469916
TI  - A mathematical model for the scaling of turbulence.
AB  - We present a simple physical model of turbulent wall-bounded shear flows that
      reveals exactly the scaling properties we had previously obtained by similarity
      considerations. The significance of our results for the understanding of
      turbulence is pointed out.

PMID- 15469915
TI  - Development of a polyclonal antiserum for the detection of the isoforms of the
      receptors for human growth hormone-releasing hormone on tumors.
AB  - Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of
      various human cancers by multiple mechanisms, which include direct effects on
      tumor cells through the splice variants (SV) of the GHRH receptor. Our findings
      suggest that the tumoral protein encoded by SV 1 (SV1) is a likely functional
      receptor. The aim of this study was to develop a polyclonal antiserum against a
      polypeptide analog of segment 1-25 of the putative SV1 receptor protein. Rabbits
      were immunized with [Ala-23]SV1 (1-25)-Tyr-26-Cys-27-NH2 as a hapten, conjugated
      to BSA or keyhole limpet hemocyanin. The antisera thus generated were evaluated
      by RIA for binding to the radiolabeled hapten. The specificity and sensitivity of
      the antisera were studied on xenografts of RL and HT human non-Hodgkin's
      lymphomas. The sera raised against keyhole limpet hemocyanin-SV1 hapten, showed
      binding values of 50-75% at a 1:56,000 dilution. In Western blot analyses, the
      purified polyclonal antibody recognized a specific signal with a molecular mass
      of approximately 40 kDa in RL and HT lymphomas. This band corresponds to the
      estimated molecular mass of the GHRH receptor isoform encoded by SV1. RT-PCR and
      ligand binding studies also revealed the expression of SV1 and the presence of
      high-affinity binding sites for GHRH on RL and HT tumors. Because the antiserum
      developed recognizes the tumoral GHRH receptor protein encoded by SV1, it should
      be of value in various investigations.

PMID- 15469917
TI  - Dimensional reduction for a Bayesian filter.
AB  - An adaptive strategy is proposed for reducing the number of unknowns in the
      calculation of a proposal distribution in a sequential Monte Carlo implementation
      of a Bayesian filter for nonlinear dynamics. The idea is to solve only in
      directions in which the dynamics is expanding, found adaptively; this strategy is
      suggested by earlier work on optimal prediction. The construction should be of
      value in data assimilation, for example, in geophysical fluid dynamics.

PMID- 15469918
TI  - Wolbachia-induced cytoplasmic incompatibility as a means for insect pest
      population control.
AB  - Biological control is the purposeful introduction of parasites, predators, and
      pathogens to reduce or suppress pest populations. Wolbachia are inherited
      bacteria of arthropods that have recently attracted attention for their potential
      as new biocontrol agents. Wolbachia manipulate host reproduction by using several
      strategies, one of which is cytoplasmic incompatibility (CI) [Stouthamer, R.,
      Breeuwer, J. A. J. & Hurst, G. D. D. (1999) Annu. Rev. Microbiol. 53, 71-102]. We
      established Wolbachia-infected lines of the medfly Ceratitis capitata using the
      infected cherry fruit fly Rhagoletis cerasi as donor. Wolbachia induced complete
      CI in the novel host. Laboratory cage populations were completely suppressed by
      single releases of infected males, suggesting that Wolbachia-induced CI could be
      used as a novel environmentally friendly tool for the control of medfly
      populations. The results also encourage the introduction of Wolbachia into pest
      and vector species of economic and hygenic relevance to suppress or modify
      natural populations.

PMID- 15469919
TI  - Cross-scale interactions, nonlinearities, and forecasting catastrophic events.
AB  - Catastrophic events share characteristic nonlinear behaviors that are often
      generated by cross-scale interactions and feedbacks among system elements. These
      events result in surprises that cannot easily be predicted based on information
      obtained at a single scale. Progress on catastrophic events has focused on one of
      the following two areas: nonlinear dynamics through time without an explicit
      consideration of spatial connectivity [Holling, C. S. (1992) Ecol. Monogr. 62,
      447-502] or spatial connectivity and the spread of contagious processes without a
      consideration of cross-scale interactions and feedbacks [Zeng, N., Neeling, J.
      D., Lau, L. M. & Tucker, C. J. (1999) Science 286, 1537-1540]. These approaches
      rarely have ventured beyond traditional disciplinary boundaries. We provide an
      interdisciplinary, conceptual, and general mathematical framework for
      understanding and forecasting nonlinear dynamics through time and across space.
      We illustrate the generality and usefulness of our approach by using new data and
      recasting published data from ecology (wildfires and desertification),
      epidemiology (infectious diseases), and engineering (structural failures). We
      show that decisions that minimize the likelihood of catastrophic events must be
      based on cross-scale interactions, and such decisions will often be
      counterintuitive. Given the continuing challenges associated with global change,
      approaches that cross disciplinary boundaries to include interactions and
      feedbacks at multiple scales are needed to increase our ability to predict
      catastrophic events and develop strategies for minimizing their occurrence and
      impacts. Our framework is an important step in developing predictive tools and
      designing experiments to examine cross-scale interactions.

PMID- 15469920
TI  - Three-body interactions improve the prediction of rate and mechanism in protein
      folding models.
AB  - Here we study the effects of many-body interactions on rate and mechanism in
      protein folding by using the results of molecular dynamics simulations on
      numerous coarse-grained Calpha-model single-domain proteins. After adding three
      body interactions explicitly as a perturbation to a Go-like Hamiltonian with
      native pairwise interactions only, we have found (i) a significantly increased
      correlation with experimental phi values and folding rates, (ii) a stronger
      correlation of folding rate with contact order, matching the experimental range
      in rates when the fraction of three-body energy in the native state is
      approximately 20%, and (iii) a considerably larger amount of three-body energy
      present in chymotripsin inhibitor than in the other proteins studied.

PMID- 15469921
TI  - Ciona intestinalis Hox gene cluster: Its dispersed structure and residual
      colinear expression in development.
AB  - Ascidians, belonging to the subphylum Urochordata, the earliest branch from the
      lineage to the vertebrates, exhibit a prototypical morphogenesis of chordates in
      the larval development, although they subsequently metamorphose into adults with
      a unique body structure. Recent draft genome analysis of the ascidian Ciona
      intestinalis has identified 9 Hox genes, which, however, have been located on
      five scaffolds. Similarly, expression patterns of Ciona Hox genes are largely
      unknown, although some data have been available for a few Hox member genes. Thus,
      the cluster structure and colinearity of Hox genes are still an enigma in C.
      intestinalis. To address these issues, we used fluorescence in situ hybridization
      and whole-mount in situ hybridization techniques and examined the genomic
      organization and spatiotemporal expression of all Hox as well as extended Hox
      member genes (Evx and Mox) of C. intestinalis. We found that seven of nine Ciona
      Hox genes are located on a single chromosome with some ordering exceptions, and
      the other genes, including Evx and Mox, are located on three other chromosomes.
      Some Ciona Hox genes, if not all, exhibited spatially coordinated expression
      within the larval central nervous system and the gut of the juvenile. In light of
      these observations, we suggest that the cluster organization and colinearity of
      the Hox genes are under dispersing and disintegrating conditions in C.
      intestinalis.

PMID- 15469922
TI  - A function of the hepatitis B virus precore protein is to regulate the immune
      response to the core antigen.
AB  - A unique characteristic of the hepatitis B virus is the production of a secreted
      form (precore or HBeAg) of the structural nucleocapsid (core or HBcAg). By using
      T cell receptor (TCR) transgenic (Tg) and TCR x HBc/HBeAg double- and triple-Tg
      pairs, we demonstrate that HBeAg elicits T cell tolerance, whereas HBcAg is
      nontolerogenic in this system. In fact, TCR x HBc double-Tg mice spontaneously
      seroconvert to IgG anti-HBc positivity at an early age. However, the presence of
      HBeAg in the serum of TCR x HBc x HBe triple-Tg mice prevents anti-HBc
      seroconversion. HBeAg mediates its immunoregulatory effect by eliciting tolerance
      in HBc/HBeAg-specific T cells. The results suggest that hepadnaviruses have
      retained a secretory form of the nucleoprotein because it functions as a T cell
      tolerogen and regulates the immune response to the intracellular nucleocapsid.
      This HBeAg-mediated immune regulation may predispose to chronicity during
      perinatal infections and prevent severe liver injury during adult infections.

PMID- 15469924
TI  - Multiple sequences in the C terminus of MaxiK channels are involved in
      expression, movement to the cell surface, and apical localization.
AB  - Apical expression of the large-conductance, calcium- and voltage-activated
      potassium (MaxiK) channel in the cortical collecting duct is responsible for flow
      stimulated potassium secretion. Here, we identify two cytoplasmic regions
      controlling apical expression of the MaxiK channel. Disruption of the proximal
      region results in the intracellular retention of the MaxiK channel without
      affecting channel assembly, thereby reducing surface expression. Coexpression of
      the WT channel with this mutant results in a reduction of WT MaxiK channel at the
      cell surface. Our data indicate that this proximal region is necessary for export
      of the MaxiK channel from the endoplasmic reticulum as a way to assess the final
      assembly of the channel. Deletion of a more distal region disrupts apical
      sorting, resulting in a nonpolarized distribution of the channel without
      impairing its surface delivery. In summary, we have found that sequences of amino
      acids in the C terminus of the MaxiK channel operate after the channel is
      assembled into a multimer and play a role in its expression, movement to the cell
      surface, and apical localization.

PMID- 15469923
TI  - Dead cells in melanoma tumors provide abundant antigen for targeted delivery of
      ionizing radiation by a mAb to melanin.
AB  - Melanoma is a cancer with a rising incidence, and metastatic disease is almost
      always lethal. We investigated the feasibility of targeting melanin, an
      intracellular melanocyte pigment, to deliver cytotoxic radiation to human
      melanoma cells in vivo by using a melanin-binding mAb (6D2). Nude mice bearing
      MNT1 pigmented human melanoma tumors were treated with mAb 6D2 labeled with 1.5
      mCi (1 Ci = 37 GBq) of the beta-emitter 188-Rhenium (188Re) and manifested
      inhibition of tumor growth and prolonged survival. mAb 6D2 bound tumor melanin
      and demonstrated no crossreactivity with normal melanized tissues in black mice.
      The mechanism of melanin targeting involved Ab binding to extracellular melanin
      released during tumor cell turnover or to dying cells with permeable membranes.
      In this approach, the cytotoxic radiation emanating from labeled Ab bound to
      melanin is presumably delivered by "crossfire" effect to the adjacent viable
      tumor cells. Our results establish the feasibility of targeting melanin released
      from dead melanoma cells in tumors with radiolabeled Abs to achieve a therapeutic
      effect. In contrast to conventional tumor antigens, melanin is insoluble,
      resistant to degradation, and can be expected to accumulate in targeted tissues,
      suggesting that the efficacy of therapy could increase with each subsequent
      treatment cycle.

PMID- 15469925
TI  - Ubiquitin-mediated fluorescence complementation reveals that Jun ubiquitinated by
      Itch/AIP4 is localized to lysosomes.
AB  - Ubiquitin family peptide modifications regulate the functions and stabilities of
      many proteins. We have developed an approach for the visualization of
      ubiquitinated proteins in living cells designated ubiquitin-mediated fluorescence
      complementation (UbFC). This approach is based on complementation among fragments
      of fluorescent proteins when they are brought together by the covalent
      conjugation of ubiquitin fused to one fragment to a substrate protein fused to a
      complementary fragment. The UbFC strategy enables simultaneous visualization of
      proteins modified by different ubiquitin family peptides and comparison of their
      effects on protein localization. Visualization of ubiquitinated Jun revealed that
      it was localized predominantly to cytoplasmic structures. In contrast, Jun
      conjugated to small ubiquitin-related modifier 1 (SUMO1) was localized to
      subnuclear foci. Comparison of the distribution of ubiquitinated Jun with markers
      for various cytoplasmic compartments revealed that ubiquitinated Jun was
      localized to lysosomal vesicles. Fractionation of cell lysates confirmed that the
      majority of ubiquitinated Jun partitioned to the cytoplasmic fraction, and
      density gradient centrifugation analysis demonstrated that it cosedimented with
      lysosomal beta-hexosaminidase activity. Mutation of a recognition sequence for
      the E3 ligase Itch/AIP4 prevented Jun ubiquitination and stabilized it in cells.
      Inhibition of lysosomal protein degradation by bafilomycin or chloroquine
      stabilized Jun but had no effect on the stability of mutated Jun that was not
      ubiquitinated by Itch/AIP4. The visualization of ubiquitinated Jun in living
      cells has uncovered a lysosomal pathway for Jun degradation that involves
      ubiquitination by Itch/AIP4.

PMID- 15469926
TI  - Sparsely populated folding intermediates of the Fyn SH3 domain: matching native
      centric essential dynamics and experiment.
AB  - A complete description of how a protein folds requires the characterization of
      intermediate conformations traversed during the folding transition. We have
      calculated dynamics trajectories of a simplified model of the Fyn SH3 domain with
      a native-centric potential energy function. Analysis of the resulting site
      resolved energy trajectory identifies an ensemble of intermediate conformations
      for folding and another for unfolding. The model's folding intermediate is
      structured in the three beta-strands that make up the protein's core and is
      strikingly similar to intermediates detected in a recent NMR study of Fyn SH3
      folding and to folding transition states elucidated in mutagenesis studies of SH3
      domains. The unfolding intermediate is formed by dissociation of the folded
      protein's two terminal beta-strands from its core. The presence of such an
      intermediate is consistent with the results of a protein-engineering study on the
      src SH3 domain showing that these strands separate before the rate-limiting step
      of unfolding. Despite the presence of these conformations intermediate between
      the native and fully unfolded states, the computed heat capacity vs. temperature
      profile of the model protein indicates that its thermodynamics satisfies the
      usual calorimetric criterion for two-state folding. This observation highlights
      the fact that, if not properly interpreted, methods such as calorimetry that do
      not probe multiple sites in a molecule can lead to an oversimplified view of
      folding. The close agreement between results from this simplified model and
      experimental work underscores the important contributions that computational
      methods can make in providing insights into protein folding.

PMID- 15469927
TI  - Left insula activation: a marker for language attainment in bilinguals.
AB  - Several lines of evidence suggest the importance of phonological working memory
      (PWM) in language acquisition. We investigated the neural correlates of PWM in
      young adults who were under compelling social pressure to be bilingual. Equal
      bilinguals had high proficiency in English and Chinese as measured by a
      standardized examination, whereas unequal bilinguals were proficient in English
      but not Chinese. Both groups were matched on several measures of nonverbal
      intelligence and working memory. In-scanner behavioral results did not show
      between-group differences. Of the regions showing load-dependent increments in
      activation, the left insula showed greater activation in equal bilinguals.
      Unequal bilinguals showed greater task-related deactivation in the anterior
      medial frontal region and greater anterior cingulate activation. Although unequal
      bilinguals kept apace with equal bilinguals in the simple PWM task, the
      differential cortical activations suggest that more optimal engagement of PWM in
      the latter may correlate with better second-language attainment.

PMID- 15469928
TI  - A universal picture of chromophores in pi-conjugated polymers derived from single
      molecule spectroscopy.
AB  - Single-molecule spectroscopy can provide insight into the fundamental
      photophysics of large macromolecules containing tens of thousands of carbon atoms
      by circumventing disorder broadening. We apply this technique to comparatively
      ordered ladder-type poly(para-phenylene) and highly disordered
      poly(phenylenevinylene) (PPV), both of which are materials of substantial
      technological interest. Identical spectroscopic features are observed on the
      single-chromophore level, independent of the chemical structure or the chain
      morphology. Both materials exhibit narrow fluorescence lines down to 0.5 nm wide,
      which we attribute to the single-chromophore zero-phonon line, accompanied by a
      discrete vibronic progression providing a signature of the chemical structure.
      The chromophore units display spectral diffusion, giving rise to dynamic disorder
      on the scale of the linewidth. Although the energetic range of spectral diffusion
      is small, it can influence intramolecular excitation energy transfer and thus the
      overall molecular emission. The spectral diffusion dynamics of single
      chromophores are identical in both material systems and follow a universal
      Gaussian distribution. In the case of emission from multiple chromophores
      situated on the molecule, which we observe for PPV, spectral diffusion follows
      Lorentzian-like statistics. The fundamental difference between the two materials
      is the possibility of coherent interchromophoric coupling in PPV, resulting in
      strong spectral broadening caused by aggregation or superradiance. Such behavior
      is absent in the ladder-type polymers, where the linewidth of the emissive
      species is identical for all molecules. Our results demonstrate that structure
      property correlations in conjugated polymers derive mainly from chain morphology
      rather than chromophoric properties and should be considered extrinsic in nature.

PMID- 15469929
TI  - Comprehensive gene expression profiles reveal pathways related to the
      pathogenesis of chronic obstructive pulmonary disease.
AB  - To better understand the molecular basis of chronic obstructive pulmonary disease
      (COPD), we used serial analysis of gene expression (SAGE) and microarray analysis
      to compare the gene expression patterns of lung tissues from COPD and control
      smokers. A total of 59,343 tags corresponding to 26,502 transcripts were
      sequenced in SAGE analyses. A total of 327 genes were differentially expressed
      (1.5-fold up- or down-regulated). Microarray analysis using the same RNA source
      detected 261 transcripts that were differentially expressed to a significant
      degree between GOLD-2 and GOLD-0 smokers. We confirmed the altered expression of
      a select number of genes by using real-time quantitative RT-PCR. These genes
      encode for transcription factors (EGR1 and FOS), growth factors or related
      proteins (CTGF, CYR61, CX3CL1, TGFB1, and PDGFRA), and extracellular matrix
      protein (COL1A1). Immunofluorescence studies on the same lung specimens localized
      the expression of Egr-1, CTGF, and Cyr61 to alveolar epithelial cells, airway
      epithelial cells, and stromal and inflammatory cells of GOLD-2 smokers. Cigarette
      smoke extract induced Egr-1 protein expression and increased Egr-1 DNA-binding
      activity in human lung fibroblast cells. Cytomix (tumor necrosis factor alpha, IL
      1beta, and IFN-gamma) treatment showed that the activity of matrix
      metalloproteinase-2 (MMP-2) was increased in lung fibroblasts from EGR1 control
      (+/+) mice but not detected in that of EGR1 null (-/-) mice, whereas MMP-9 was
      regulated by EGR1 in a reverse manner. Our study represents the first
      comprehensive analysis of gene expression on GOLD-2 versus GOLD-0 smokers and
      reveals previously unreported candidate genes that may serve as potential
      molecular targets in COPD.

PMID- 15469930
TI  - Nonvesicular release of acetylcholine is required for axon targeting in the
      Drosophila visual system.
AB  - We report evidence for a developmental role of acetylcholine in axon pathfinding
      in the Drosophila visual system. Acetylcholine was detected on photoreceptor
      axons during their navigation to target sites in the brain, a time well before
      the formation of functional synapses. The pattern of photoreceptor axon
      projections was severely disrupted when acetylcholine synthesis or metabolism was
      altered or eliminated, or when transgenic alpha-bungarotoxin, a nicotinic
      acetylcholine receptor antagonist, was expressed in the developing eye or brain.
      The requirement for acetylcholine signaling exists before photoreceptor neurons
      form synaptic connections and does not require the function of vesicular
      acetylcholine transporter protein. That this early effect of acetylcholine is
      mediated through nonvesicular release is further supported by the observation
      that transgenic expression of tetanus toxin, a blocker of neurotransmitter
      release via synaptic vesicles, did not cause similar photoreceptor axon
      projection defects. These observations support the notion that a form of
      acetylcholine secretion mediates the behavior of growth cones during axon
      pathfinding.

PMID- 15469931
TI  - The crystal structure of transthyretin in complex with diethylstilbestrol: a
      promising template for the design of amyloid inhibitors.
AB  - Transthyretin (TTR) is a homotetrameric plasma protein that, in conditions not
      yet completely understood, may aggregate, forming the fibrillar material
      associated with TTR amyloidosis. A number of reported experiments indicate that
      dissociation of the TTR tetramer occurs prior to fibril formation, and therefore,
      studies aiming at the discovery of compounds that stabilize the protein
      quaternary structure, thereby acting as amyloid inhibitors, are being performed.
      The ability of diethylstilbestrol (DES) to act as a competitive inhibitor for the
      thyroid hormone binding to TTR indicated a possible stabilizing effect of DES
      upon binding. Here we report the crystallographic study of DES binding to TTR.
      The structural data reveal two different binding modes, both located in the
      thyroxine binding channel. In both cases, DES binds deeply in the channel and
      establishes interactions with the equivalent molecule present in the adjacent
      binding site. The most remarkable features of DES interaction with TTR are its
      hydrophobic interactions within the protein halogen binding pockets, where its
      ethyl groups are snugly fitted, and the hydrogen bonds established at the center
      of the tetramer with Ser-117. Experiments concerning amyloid formation in vitro
      suggest that DES is effectively an amyloid inhibitor in acid-mediated
      fibrillogenesis and may be used for the design of more powerful drugs. The
      present study gave us further insight in the molecular mechanism by which DES
      competes with thyroid hormone binding to TTR and highlights key interactions
      between DES and TTR that oppose amyloid formation.

PMID- 15469932
TI  - A dileucine motif and a cluster of acidic amino acids in the second cytoplasmic
      domain of the batten disease-related CLN3 protein are required for efficient
      lysosomal targeting.
AB  - The juvenile form of ceroid lipofuscinosis (Batten disease) is a
      neurodegenerative lysosomal storage disorder caused by mutations in the CLN3
      gene. CLN3 encodes a multimembrane-spanning protein of unknown function, which is
      mainly localized in lysosomes in non-neuronal cells and in endosomes in neuronal
      cells. For this study we constructed chimeric proteins of three CLN3 cytoplasmic
      domains fused to the lumenal and transmembrane domains of the reporter proteins
      LAMP-1 and lysosomal acid phosphatase to identify lysosomal targeting motifs and
      to determine the intracellular transport and subcellular localization of the
      chimera in transfected cell lines. We report that a novel type of dileucine-based
      sorting motif, EEEX(8)LI, present in the second cytoplasmic domain of CLN3, is
      sufficient for proper targeting to lysosomes. The first cytoplasmic domain of
      CLN3 and the mutation of the dileucine motif resulted in a partial missorting of
      chimeric proteins to the plasma membrane. At equilibrium, 4-13% of the different
      chimera are present at the cell surface. Analysis of lysosome-specific
      proteolytic processing revealed that lysosomal acid phosphatase chimera
      containing the second cytoplasmic domain of CLN3 showed the highest rate of
      lysosomal delivery, whereas the C terminus of CLN3 was found to be less efficient
      in lysosomal targeting. However, none of these cytosolic CLN3 domains was able to
      interact with AP-1, AP-3, or GGA3 adaptor complexes. These data revealed that
      lysosomal sorting motifs located in an intramolecular cytoplasmic domain of a
      multimembrane-spanning protein have different structural requirements for adaptor
      binding than sorting signals found in the C-terminal cytoplasmic domains of
      single- or dual-spanning lysosomal membrane proteins.

PMID- 15469933
TI  - Secreted protein acidic, rich in cysteine (SPARC), mediates cellular survival of
      gliomas through AKT activation.
AB  - Secreted protein acidic, rich in cysteine (SPARC), is an extracellular matrix
      protein expressed in many advanced cancers, including malignant gliomas. We and
      others have previously shown that human glioma cell lines engineered to
      overexpress SPARC adopt an invasive phenotype. We now show that SPARC expression
      increases cell survival under stress initiated by serum withdrawal through a
      decrease in apoptosis. Phosphatidylinositol 3-OH kinase/AKT is a potent pro
      survival pathway that contributes to the malignancy of gliomas. Cells expressing
      SPARC display increased AKT activation with decreased caspase 3/7 activity.
      Exogenous SPARC rapidly induces AKT phosphorylation, an effect that is blocked by
      a neutralizing SPARC antibody. Furthermore, AKT activation is essential for the
      anti-apoptotic effects of SPARC as the decreased apoptosis and caspase activity
      associated with SPARC expression can be blocked with dominant-negative AKT or a
      specific AKT inhibitor. As tumor cells face stressful microenvironments
      particularly during the process of invasion, these results suggest that SPARC
      functions, in part, to promote tumor progression by enabling tumor cells to
      survive under stressful conditions.

PMID- 15469934
TI  - Identification and characterization of the IKKalpha promoter: positive and
      negative regulation by ETS-1 and p53, respectively.
AB  - IKKalpha, a subunit of IkBalpha kinase (IKK) complex, has an important role in
      the activation of nuclear factor-kB (NF-kB), a key regulator of normal and tumor
      cell proliferation, apoptosis, and response to chemotherapy. However, little is
      known about the transcriptional regulation of the IKKalpha gene itself. The
      present study revealed that the transcriptional induction of the IKKalpha gene is
      positively regulated by binding ETS-1, the protein product of the ETS-1 proto
      oncogene. Furthermore, ETS-1 mediated activation of IKKalpha is negatively
      regulated by p53 binding to ETS-1. By analyzing the genomic DNA sequence, we
      identified the putative IKKalpha promoter sequence in the 5'-flanking
      untranslated region of the IKKalpha gene. Transfection of EU-4, an acute
      lymphoblastic leukemia (ALL) cell line, with plasmids containing the IKKalpha 5'
      untranslated region sequence upstream of the luciferase reporter showed that this
      region possessed major promoter activity. Induction or enforced overexpression of
      p53 represses IKKalpha mRNA and protein expression as well as IKKalpha promoter
      activity. Deletion and mutation analyses as well as chromatin immunoprecipitation
      and electrophoretic mobility shift assay indicated that ETS-1 binds to the core
      IKKalpha promoter and strongly induces its activity. Although p53 does not
      directly bind to the IKKalpha promoter, it physically interacts with ETS-1 and
      specifically inhibits ETS-1-induced IKKalpha promoter activity. These results
      suggest that the proximal 5'-flanking region of the IKKalpha gene contains a
      functional promoter reciprocally regulated by p53 and ETS-1. Furthermore, loss of
      p53-mediated control over ETS-1-dependent transactivation of IKKalpha may
      represent a novel pathway for the constitutive activation of NF-kB-mediated gene
      expression and therapy resistance in cancer.

PMID- 15469935
TI  - Mutational analysis of putative calcium binding motifs within the skeletal
      ryanodine receptor isoform, RyR1.
AB  - The functional relevance of putative Ca(2+) binding motifs previously identified
      with Ca(2+) overlay binding analysis within the skeletal muscle ryanodine
      receptor isoform (RyR1) was examined using mutational analysis. EF hands between
      amino acid positions 4081 and 4092 (EF1) and 4116 and 4127 (EF2) were scrambled
      singly or in combination within the full-length rabbit RyR1 cDNA. These cDNAs
      were expressed in 1B5 RyR-deficient myotubes and channel function assessed using
      Ca(2+)-imaging techniques, [(3)H]ryanodine binding measurements, and single
      channel experiments. In intact myotubes, these mutations did not affect
      functional responses to either depolarization or RyR agonists (caffeine, 4-chloro
      m-cresol) compared with wtRyR1. However, in [(3)H]ryanodine binding measurements,
      both Ca(2+) activation and inhibition of the EF1 mutant was significantly altered
      compared with wtRyR1. No high affinity [(3)H]ryanodine binding was observed in
      membranes expressing the EF2 mutation, although in single channel measurements,
      the EF2-disrupted channel could be activated by micromolar Ca(2+) concentrations.
      In addition, micromolar levels of ryanodine placed these channels into the
      classical half-conductance state, thus indicating that occupancy of high affinity
      ryanodine binding sites is not required for ryanodine-induced subconductance
      states in RyR1. Disruption of three additional putative RyR1 calcium binding
      motifs located between amino acid positions 4254 and 4265 (EF3), 4407 and 4418
      (EF4), or 4490 and 4502 (EF5) either singly or in combination (EF3-5) did not
      affect functional responses in 1B5 myotubes except that the EC(50) for caffeine
      activation for the EF3 construct was significantly increased compared with
      wtRyR1. However, in [(3)H]ryanodine binding experiments, the Ca(2+)-dependent
      activation and inactivation of mutated RyRs containing EF3, EF4, or EF5 was
      unaffected when compared with wtRyR1.

PMID- 15469936
TI  - Structural determinants of the anti-HIV activity of a CCR5 antagonist derived
      from Toxoplasma gondii.
AB  - The protozoan parasite Toxoplasma gondii possesses a protein, cyclophilin-18 (C
      18), which binds to the chemokine receptor CCR5, induces interleukin-12
      production from murine dendritic cells, and inhibits fusion and infectivity of
      human immunodeficiency virus 1 (HIV-1) R5 viruses by co-receptor antagonism. Site
      directed mutagenesis was employed to identify the domains in C-18 responsible for
      its CCR5 binding and antiviral functions. To do so we focused on amino acid
      differences with Plasmodium falciparum cyclophilin, which, although 53% identical
      with C-18, has minimal binding activity for CCR5, and we generated 22 mutants
      with substitutions in the regions of non-homology located on the putative surface
      of the molecule. Two mutations situated on the face of C-18, predicted to be
      involved in its interaction with the ligand cyclosporin A, were shown to be
      critical for CCR5-binding and the inhibition of HIV-1 fusion and infectivity. In
      contrast, four mutations in C-18 specifically designed to abolish the peptidyl
      prolyl cis-trans-isomerase activity of the protein failed to inactivate its CCR5
      binding and HIV inhibitory activities. Interleukin-12 induction by C-18, on the
      other hand, was abrogated by mutations effecting either the CCR5 binding or
      enzymatic function of the molecule. These findings shed light on the structural
      basis of the molecular mimicry of the chemokine function by a pathogen-derived
      protein and provide a basis for further modification of C-18 into an antiviral
      agent.

PMID- 15469937
TI  - Mouse very long-chain Acyl-CoA synthetase 3/fatty acid transport protein 3
      catalyzes fatty acid activation but not fatty acid transport in MA-10 cells.
AB  - The family of proteins that includes very long-chain acyl-CoA synthetases (ACSVL)
      consists of six members. These enzymes have also been designated fatty acid
      transport proteins. We cloned full-length mouse Acsvl3 cDNA and characterized its
      protein product ACSVL3/fatty acid transport protein 3. The predicted amino acid
      sequence contains two highly conserved motifs characteristic of acyl-CoA
      synthetases. Northern blot analysis revealed that the mouse Acsvl3 mRNA is highly
      expressed in adrenal gland, testis, and ovary, with lower expression in the brain
      of adult mice. A developmental Northern blot revealed that Acsvl3 mRNA levels
      were significantly higher in embryonic mouse brain (embryonic days 12-14) than in
      newborn or adult mice, suggesting a possible role in nervous system development.
      Immunohistochemistry revealed high ACSVL3 expression in adrenal cortical cells,
      spermatocytes and interstitial cells of the testis, theca cells of the ovary,
      cerebral cortical neurons, and cerebellar Purkinje cells. Endogenous ACSVL3 was
      found primarily in mitochondria of MA-10 and Neuro2a cells by both Western blot
      analysis of subcellular fractions and immunofluorescence analysis. In MA-10
      cells, loss-of-function studies using RNA interference confirmed that endogenous
      ACSVL3 is an acyl-CoA synthetase capable of activating both long-chain (C16:0)
      and very long-chain (C24:0) fatty acids. However, despite decreased acyl-CoA
      synthetase activity, initial rates of fatty acid uptake were unaffected by
      knockdown of Acsvl3 expression in MA-10 cells. These studies cast doubt on the
      designation of ACSVL3 as a fatty acid transport protein.

PMID- 15469938
TI  - Inhibition of calcium/calmodulin-dependent protein kinase kinase by protein 14-3
      3.
AB  - Intracellular calcium concentrations regulate diverse cellular events including
      cytoskeletal dynamics, gene transcription, and synaptic plasticity. The calcium
      signal is transduced in part by the calcium/calmodulin-dependent protein kinase
      (CaMK) cascade that is comprised of CaMK kinase (CaMKK) and its primary
      downstream substrates, CaMKI and CaMKIV. The CaMK cascade also participates in
      cross-talk with other signaling pathways: CaMKK/CaMKI can activate the mitogen
      activated protein kinase pathway and cAMP-dependent protein kinase (PKA) can
      directly phosphorylate two inhibitory sites (Thr108 and Ser458) in CaMKK. Here we
      report an additional PKA-dependent regulation of CaMKK through its interaction
      with protein 14-3-3. CaMKK and 14-3-3 co-immunoprecipitated from co-transfected
      heterologous cells as well as from rat brain homogenate, and site-directed
      mutagenesis studies identified phospho-Ser74 in CaMKK as the primary 14-3-3
      binding site. In cultured rat hippocampal neurons and acute hippocampal slices
      this interaction was robustly stimulated by activation of PKA through forskolin
      treatment and was blocked by inhibition of PKA. Interaction of 14-3-3 with CaMKK
      had two regulatory consequences in vitro. It directly inhibited CaMKK activity,
      and it also blocked dephosphorylation of Thr108, an inhibitory PKA
      phosphorylation site. In human embryonic kidney 293 cells transfected with CaMKK
      and stimulated with forskolin, co-transfection with 14-3-3 prevented
      dephosphorylation of Thr108 to the same extent as did inhibition of protein
      phosphatases with okadaic acid. We conclude that binding of 14-3-3 to CaMKK
      stabilizes its inhibition by PKA-mediated phosphorylation, which may have
      important consequences in the regulation of CaMKI, CaMKIV, protein kinase B, and
      ERK signaling pathways.

PMID- 15469939
TI  - Distinct mechanisms of neurodegeneration induced by chronic complex I inhibition
      in dopaminergic and non-dopaminergic cells.
AB  - Chronic mitochondrial dysfunction, in particular of complex I, has been strongly
      implicated in the dopaminergic neurodegeneration in Parkinson's disease. To
      elucidate the mechanisms of chronic complex I disruption-induced
      neurodegeneration, we induced differentiation of immortalized midbrain
      dopaminergic (MN9D) and non-dopaminergic (MN9X) neuronal cells, to maintain them
      in culture without significant cell proliferation and compared their survivals
      following chronic exposure to nanomolar rotenone, an irreversible complex I
      inhibitor. Rotenone killed more dopaminergic MN9D cells than non-dopaminergic
      MN9X cells. Oxidative stress played an important role in rotenone-induced
      neurodegeneration of MN9X cells, but not MN9D cells: rotenone oxidatively
      modified proteins more in MN9X cells than in MN9D cells and antioxidants
      decreased rotenone toxicity only in MN9X cells. MN9X cells were also more
      sensitive to exogenous oxidants than MN9D cells. In contrast, disruption of
      bioenergetics played a more important role in MN9D cells: rotenone decreased
      mitochondrial membrane protential and ATP levels in MN9D cells more than in MN9X
      cells. Supplementation of cellular energy with a ketone body, D-beta
      hydroxybutyrate, decreased rotenone toxicity in MN9D cells, but not in MN9X
      cells. MN9D cells were also more susceptible to disruption of oxidative
      phosphorylation or glycolysis than MN9X cells. These findings indicate that,
      during chronic rotenone exposure, MN9D cells die primarily through mitochondrial
      energy disruption, whereas MN9X cells die primarily via oxidative stress. Thus,
      intrinsic properties of individual cell types play important roles in determining
      the predominant mechanism of complex I inhibition-induced neurodegeneration.

PMID- 15469940
TI  - Aurora-A abrogation of p53 DNA binding and transactivation activity by
      phosphorylation of serine 215.
AB  - The tumor suppressor p53 is important in the decision to either arrest cell cycle
      progression or induce apoptosis in response to a variety of stimuli. p53
      posttranslational modifications and association with other proteins have been
      implicated in the regulation of its stability and transactivation activity. Here
      we show that p53 is phosphorylated by the mitotic kinase Aurora-A at serine 215.
      Unlike most identified phosphorylation sites of p53 that positively associate
      with p53 function (Brooks, C. L., and Gu, W. (2003) Curr. Opin. Cell Biol. 15,
      164-171), the phosphorylation of p53 by Aurora-A at Ser-215 abrogates p53 DNA
      binding and transactivation activity. Downstream target genes of p53, such as
      p21Cip/WAF1 and PTEN, were inhibited by Aurora-A in a Ser-215 phosphorylation
      dependent manner (i.e. phosphomimic p53-S215D lost and non-phosphorylatable p53
      S215A retained normal p53 function). As a result, Aurora-A overrides the
      apoptosis and cell cycle arrest induced by cisplatin and gamma-irradiation,
      respectively. However, the effect of Aurora-A on p53 DNA binding and
      transactivation activity was not affected by phosphorylation of Ser-315, a
      recently identified Aurora-A phosphorylation site of p53 (Katayama, H., Sasai,
      K., Kawai, H., Yuan, Z. M., Bondaruk, J., Suzuki, F., Fujii, S., Arlinghaus, R.
      B., Czerniak, B. A., and Sen, S. (2004) Nat. Genet. 36, 55-62). Our data indicate
      that phosphorylation of p53 at Ser-215 by Aurora-A is a major mechanism to
      inactivate p53 and can provide a molecular insight for Aurora-A function.

PMID- 15469941
TI  - Peroxisomal proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1
      alpha) enhances the thyroid hormone induction of carnitine palmitoyltransferase I
      (CPT-I alpha).
AB  - Carnitine palmitoyltransferase I (CPT-I) catalyzes the rate-controlling step in
      the pathway of mitochondrial fatty acid oxidation. Thyroid hormone will stimulate
      the expression of the liver isoform of CPT-I (CPT-I alpha). This induction of CPT
      I alpha gene expression requires the thyroid hormone response element in the
      promoter and sequences within the first intron. The peroxisomal proliferator
      activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is a coactivator that
      promotes mitochondrial biogenesis, mitochondrial fatty acid oxidation, and
      hepatic gluconeogenesis. In addition, PGC-1 alpha will stimulate the expression
      of CPT-I alpha in primary rat hepatocytes. Here we report that thyroid hormone
      will increase PGC-1 alpha mRNA and protein levels in rat hepatocytes. In
      addition, overexpression of PGC-1 alpha will enhance the thyroid hormone
      induction of CPT-I alpha indicating that PGC-1 alpha is a coactivator for thyroid
      hormone. By using chromatin immunoprecipitation assays, we show that PGC-1 alpha
      is associated with both the thyroid hormone response element in the CPT-I alpha
      gene promoter and the first intron of the CPT-I alpha gene. Our data demonstrate
      that PGC-1 alpha participates in the stimulation of CPT-I alpha gene expression
      by thyroid hormone and suggest that PGC-1 alpha is a coactivator for thyroid
      hormone.

PMID- 15469943
TI  - Seasonal and annual stem respiration of Scots pine trees under boreal conditions.
AB  - BACKGROUND AND AIMS: Stem respiration of trees is a major, but poorly assessed
      component of the carbon balance of forests, and important for geo-chemistry.
      Measurements are required under naturally changing seasonal conditions in
      different years. Therefore, intra- and inter-annual carbon fluxes of stems in
      forests were measured continuously from April to November in three consecutive
      years. METHODS: Stem respiratory CO2 fluxes of 50-year-old Scots pine (Pinus
      sylvestris) trees were continuously measured with a CO2 analyser, and,
      concomitantly, stem circumference, stem and air temperature and other
      environmental factors and photosynthesis, were also measured automatically. KEY
      RESULTS: There were diurnal, seasonal and inter-annual changes in stem
      respiration, which peaked at 1600 h during the day and was highest in July. The
      temperature coefficient of stem respiration (Q10) was greater during the growing
      season than when growth was slow or had stopped, and more sensitive to
      temperature in the growing season. The annual Q10 remained relatively constant at
      about 2 over the three years, while respiration at a reference temperature of 15
      degrees C (R15) was higher in the growing than in the non-growing season (1.09
      compared with 0.78 micromol m(-2) stem surface s(-1)), but was similar between
      the years. Maintenance respiration was 76 %, 82 % and 80 % of the total
      respiration of 17.46, 17.26 and 19.35 mol m2 stem surface in 2001, 2002 and 2003,
      respectively. The annual total stem respiration of the stand per unit ground area
      was 75.97 gC m(-2) in 2001 and 74.28 gC m(-2) in 2002. CONCLUSIONS: Stem
      respiration is an important component in the annual carbon balance of a Scots
      pine stand, contributing 9 % to total carbon loss from the ecosystem and
      consuming about 8 % of the carbon of the ecosystem gross primary production. Stem
      (or air) temperature was the most important predictor of stem carbon flux. The
      magnitude of stem respiration is modified by photosynthesis and tree growth.
      Solar radiation indirectly affects stem respiration through its effect on
      photosynthesis.

PMID- 15469942
TI  - Identification and functional characterization of a novel human misshapen/Nck
      interacting kinase-related kinase, hMINK beta.
AB  - Misshapen/NIKs-related kinase (MINK) is a member of the germinal center family of
      kinases that are homologous to the yeast sterile 20 (Ste20) kinases and regulate
      a wide variety of cellular processes, including cell morphology, cytoskeletal
      rearrangement, and survival. Here, we present the cloning and functional
      characterization of a novel human Misshapen/NIKs-related kinase beta (hMINK beta)
      that encodes a polypeptide of 1312 amino acids. hMINK beta is ubiquitously
      expressed in most tissues with at least five alternatively spliced isoforms.
      Similar to Nck interacting kinase (NIK) and Traf2 and Nck-interacting kinase
      (TNIK), hMINK beta moderately activates c-Jun N-terminal kinase (JNK) and
      associates with Nck via the intermediate domain in the yeast two-hybrid system
      and in a glutathione S-transferase (GST) pull-down assay. Interestingly,
      overexpression of the kinase domain deleted and kinase-inactive mutants of hMINK
      beta in human fibrosarcoma HT1080 cells enhanced cell spreading, actin stress
      fiber formation, and adhesion to extracellular matrix, as well as decreased cell
      motility and cell invasion. Furthermore, these mutants also promoted cell-cell
      adhesion in human breast carcinoma MCF7 cells, evidenced with cell growth in
      clusters and increased membrane localization of beta-catenin, a multifunctional
      protein involved in E-cadherin-mediated cell adhesion. Finally, hMINK beta
      protein was found to colocalize with the Golgi apparatus, implicating that hMINK
      beta might exert its functions, at least in part, through the modulation of
      intracellular protein transport. Taken together, these results suggest that hMINK
      beta plays an important role in cytoskeleton reorganization, cell adhesion, and
      cell motility.

PMID- 15469944
TI  - Quantitative and qualitative differences in morphological traits revealed between
      diploid Fragaria species.
AB  - BACKGROUND AND AIMS: The aims of this investigation were to highlight the
      qualitative and quantitative diversity apparent between nine diploid Fragaria
      species and produce interspecific populations segregating for a large number of
      morphological characters suitable for quantitative trait loci analysis. METHODS:
      A qualitative comparison of eight described diploid Fragaria species was
      performed and measurements were taken of 23 morphological traits from 19
      accessions including eight described species and one previously undescribed
      species. A principal components analysis was performed on 14 mathematically
      unrelated traits from these accessions, which partitioned the species accessions
      into distinct morphological groups. Interspecific crosses were performed with
      accessions of species that displayed significant quantitative divergence and,
      from these, populations that should segregate for a range of quantitative traits
      were raised. KEY RESULTS: Significant differences between species were observed
      for all 23 morphological traits quantified and three distinct groups of species
      accessions were observed after the principal components analysis. Interspecific
      crosses were performed between these groups, and F2 and backcross populations
      were raised that should segregate for a range of morphological characters. In
      addition, the study highlighted a number of distinctive morphological characters
      in many of the species studied. CONCLUSIONS: Diploid Fragaria species are
      morphologically diverse, yet remain highly interfertile, making the group an
      ideal model for the study of the genetic basis of phenotypic differences between
      species through map-based investigation using quantitative trait loci. The
      segregating interspecific populations raised will be ideal for such
      investigations and could also provide insights into the nature and extent of
      genome evolution within this group.

PMID- 15469945
TI  - Childhood predictors of self reported chronic fatigue syndrome/myalgic
      encephalomyelitis in adults: national birth cohort study.
AB  - OBJECTIVE: To study childhood risk factors for chronic fatigue syndrome in adult
      life. DESIGN: Examination of data from the 1970 British birth cohort.
      PARTICIPANTS: 16,567 babies born 5-11 April 1970, followed up at 5, 10, 16, and
      29-30 years. MAIN OUTCOME MEASURES: Chronic fatigue syndrome/myalgic
      encephalomyelitis (CFS/ME) identified by self report at age 30 years. Data from
      childhood from questionnaires given to parents and teachers. Maternal mental
      health assessed with the malaise inventory. RESULTS: 93 (0.8%, 95% confidence
      interval 0.7 to 1.0) of 11 261 participants reported ever having CFS/ME, and 48
      (0.4%, 0.3 to 0.6) had the condition currently. Higher risk of CFS/ME was
      associated with having a limiting longstanding condition in childhood (odds ratio
      2.3, 1.4 to 3.9), female sex (2.3, 1.4 to 2.6), and high social class in
      childhood (2.2, 1.4 to 3.5). Higher levels of exercise in childhood were
      associated with lower risk (0.5, 0.2 to 0.9). Maternal psychological disorder,
      psychological problems in childhood, birth weight, birth order, atopy, obesity,
      school absence, academic ability, and parental illness were not associated with
      risk of CFS/ME. CONCLUSIONS: We identified no association between maternal or
      child psychological distress, academic ability, parental illness, atopy, or birth
      order and increasing risk of lifetime CFS/ME. Sedentary behaviour increased the
      risk.

PMID- 15469946
TI  - Issues in the reporting of epidemiological studies: a survey of recent practice.
AB  - OBJECTIVES: To review current practice in the analysis and reporting of
      epidemiological research and to identify limitations. DESIGN: Examination of
      articles published in January 2001 that investigated associations between risk
      factors/exposure variables and disease events/measures in individuals. SETTING:
      Eligible English language journals including all major epidemiological journals,
      all major general medical journals, and the two leading journals in
      cardiovascular disease and cancer. MAIN OUTCOME MEASURE: Each article was
      evaluated with a standard proforma. RESULTS: We found 73 articles in
      observational epidemiology; most were either cohort or case-control studies. Most
      studies looked at cancer and cardiovascular disease, even after we excluded
      specialty journals. Quantitative exposure variables predominated, which were
      mostly analysed as ordered categories but with little consistency or explanation
      regarding choice of categories. Sample selection, participant refusal, and data
      quality received insufficient attention in many articles. Statistical analyses
      commonly used odds ratios (38 articles) and hazard/rate ratios (23), with some
      inconsistent use of terminology. Confidence intervals were reported in most
      studies (68), though use of P values was less common (38). Few articles explained
      their choice of confounding variables; many performed subgroup analyses claiming
      an effect modifier, though interaction tests were rare. Several investigated
      multiple associations between exposure and outcome, increasing the likelihood of
      false positive claims. There was evidence of publication bias. CONCLUSIONS: This
      survey raises concerns regarding inadequacies in the analysis and reporting of
      epidemiological publications in mainstream journals.

PMID- 15469947
TI  - Reasons for considering leaving UK medicine: questionnaire study of junior
      doctors' comments.
AB  - OBJECTIVES: To study the reasons given by junior doctors trained in the United
      Kingdom for considering leaving UK medicine. DESIGN: Analysis of replies to
      postal questionnaire surveys. SETTING: United Kingdom. PARTICIPANTS: 1326 doctors
      who qualified in 1999. MAIN OUTCOME MEASURE: Reasons for considering leaving.
      RESULTS: Of 1047 doctors who indicated that they would stay in medicine but not
      necessarily in the United Kingdom, 65% (682) gave reasons for leaving that
      concerned lifestyle, such as a preference for living outside the United Kingdom;
      41% (433) gave reasons concerning working conditions in UK medicine; and 18%
      (184) gave positive work related reasons, such as wanting to work in developing
      countries. Of 279 doctors considering leaving medicine, 75% (210) cited working
      conditions, 23% (63) cited lifestyle reasons, and 9% (24) cited positive
      interests in a different career. Of the 169 doctors who said that they would
      probably or definitely leave the United Kingdom but remain in medicine, 78% (132)
      specified lifestyle reasons. Of the 42 who said that they would probably or
      definitely leave medicine, 67% (28) cited working conditions. CONCLUSIONS: The
      wish to work abroad, but to stay in medicine, was more common than the wish to
      leave medicine. The preference for a different lifestyle, particularly to live
      outside the United Kingdom, is not readily amenable to policy changes to the
      medical working environment. The smaller numbers of doctors who gave work
      experience as a reason for considering leaving medicine might be influenced to
      stay by improvements in working lives.

PMID- 15469948
TI  - Caffeic acid phenethyl ester prevents neonatal hypoxic-ischaemic brain injury.
AB  - Neonatal hypoxic-ischaemic (HI) brain injury resulting in encephalopathy is a
      leading cause of morbidity and mortality with no effective treatment. Here we
      show that caffeic acid phenethyl ester (CAPE), an active component of propolis,
      administered either before or after an HI insult, significantly prevents HI
      induced neonatal rat brain damage in the cortex, hippocampus and thalamus. In
      addition to blocking HI-induced caspase 3 activation, CAPE also inhibits HI
      mediated expression of inducible nitric oxide synthase and caspase 1 in vivo and
      potently blocks nitric oxide-induced neurotoxicity in vitro. Furthermore, CAPE
      directly inhibits Ca2+-induced cytochrome c release from isolated brain
      mitochondria. Thus, CAPE induces neuroprotection against HI-induced neuronal
      death, possibly by blocking HI-induced inflammation and/or directly inhibiting
      the HI-induced neuronal death pathway. CAPE may therefore be a novel effective
      therapy for preventing neonatal HI injury.

PMID- 15469949
TI  - Clinicopathological and genetic study of early-onset demyelinating neuropathy.
AB  - Autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT4), Dejerine
      Sottas disease and congenital hypomyelinating neuropathy are variants of
      hereditary demyelinating neuropathy of infancy, a genetically heterogeneous group
      of disorders. To explore the spectrum of early-onset demyelinating neuropathies
      further, we studied the clinicopathological and genetic aspects of 20 patients
      born to unaffected parents. In 19 families out of 20, consanguinity between the
      parents or presence of an affected sib suggested autosomal recessive
      transmission. Screening of various genes known to be involved in CMT4 revealed
      six mutations of which five are novel. Four of these novel mutations occurred in
      the homozygous state and include: one in GDAP1, one in MTMR2, one in PRX and one
      in KIAA1985. One patient was heterozygous for a novel MTMR2 mutation and still
      another was homozygous for the founder mutation, R148X, in NDRG1. All patients
      tested negative for mutations in EGR2. Histopathological examination of nerve
      biopsy specimens showed a severe, chronic demyelinating neuropathy, with onion
      bulb formation, extensive demyelination of isolated fibres and axon loss. We did
      not discern a specific pattern of histopathology that could be correlated to
      mutations in a particular gene.

PMID- 15469950
TI  - A study of bipolar disorder using magnetization transfer imaging and voxel-based
      morphometry.
AB  - Bipolar disorder (BP) traditionally has been considered as a recurrent illness
      with full recovery between episodes, and the absence of neuropathological
      abnormalities has usually been taken for granted. In recent times, the
      realization that, for many BP carries a poor prognosis, that cognitive deficits
      are often persistent and that structural brain abnormalities are detectable with
      modern imaging techniques has spurred the search for its neuropathological
      substrate. The shortcomings of post-mortem studies make the use of imaging
      techniques sensitive to neuropathological changes compelling. We report here the
      first study of BP patients using two such techniques in conjunction:
      magnetization transfer imaging (MTI) and voxel-based morphometry (VBM). Thirty
      nine patients with BP (13 males and 26 females; 28 with BPI and 11 with BPII) and
      35 healthy controls were investigated. Both high-resolution volumetric T1
      weighted images and MT images were acquired from all subjects. Images were
      processed using a voxel-by-voxel analysis in statistical parametric mapping 2
      (SPM2). The magnetization transfer ratio MTR, an index indicative of loss of
      macromolecular density, was reduced in the right subgenual anterior cingulate and
      adjacent white matter in bipolar patients compared with controls. VBM did not
      reveal significant volumetric differences between BP patients and controls in
      grey and white matter, but white matter density was significantly reduced
      bilaterally in prefrontal areas encompassing fronto-striatal connections. Our
      findings suggest that subtle abnormalities are present in the anterior cingulate
      and subgyral white matter in patients with BP in the absence of significant
      volumetric changes. These findings are in keeping with those of previously
      reported neuropathological studies and illustrate important similarities
      (involvement of the anterior cingulate) and differences (lack of widespread
      cortical abnormalities in BP) with our previous studies in schizophrenic patients
      using the same methodology.

PMID- 15469951
TI  - Wild-type bone marrow cells ameliorate the phenotype of SOD1-G93A ALS mice and
      contribute to CNS, heart and skeletal muscle tissues.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative
      disease without any effective therapy. To evaluate the potential of wild-type
      bone marrow (BM)-derived stem cells to modify the ALS phenotype, we generated BM
      chimeric Cu/Zn superoxide dismutase (SOD1) mice by transplantation of BM cells
      derived from mice expressing green fluorescent protein (GFP) in all tissues and
      from Thy1-YFP mice that express a spectral variant of GFP (yellow fluorescent
      protein) in neurons only. In the recipient cerebral cortex, we observed rare GFP+
      and YFP+ neurons, which were probably generated by cell fusion, as demonstrated
      by fluorescence in situ hybridization (FISH) analysis, suggesting that this
      phenomenon is not limited to Purkinje cells. GFP-positive microglial cells were
      extensively present in both the brain and spinal cord of the affected animals.
      Completely differentiated and immature GFP+ myofibres were also present in the
      heart and skeletal muscles of SOD1 mice, confirming that BM cells can participate
      in striated muscle tissue regeneration. Moreover, wild-type BM chimeric SOD1 mice
      showed a significantly delayed disease onset and an increased life span, probably
      due to a positive 'non-neuronal environmental' effect rather than to
      neuronogenesis. This improvement in SOD1-G93A mouse survival is comparable with
      that previously obtained using some safer pharmacological agents. BM
      transplantation-related complications in humans preclude its clinical application
      for ALS treatment. However, our data suggest that further studies aimed at
      improving the degree of tissue chimerism by BM-derived cells may provide valuable
      insights into strategies to slow ALS progression.

PMID- 15469952
TI  - Skeletal muscle fiber atrophy: altered thin filament density changes slow fiber
      force and shortening velocity.
AB  - Single skinned fibers from soleus and adductor longus (AL) muscles of weight
      bearing control rats and rats after 14-day hindlimb suspension unloading (HSU)
      were studied physiologically and ultrastructurally to investigate how slow fibers
      increase shortening velocity (V0) without fast myosin. We hypothesized that
      unloading and shortening of soleus during HSU reduces densities of thin
      filaments, generating wider myofilament separations that increase V0 and decrease
      specific tension (kN/m2). During HSU, plantarflexion shortened soleus working
      length 23%. AL length was unchanged. Both muscles atrophied as shown by
      reductions in fiber cross-sectional area. For AL, the 60% atrophy accounted fully
      for the 58% decrease in absolute tension (mN). In the soleus, the 67% decline in
      absolute tension resulted from 58% atrophy plus a 17% reduction in specific
      tension. Soleus fibers exhibited a 25% reduction in thin filaments, whereas there
      was no change in AL thin filament density. Loss of thin filaments is consistent
      with reduced cross bridge formation, explaining the fall in specific tension. V0
      increased 27% in soleus but was unchanged in AL. The V0 of control and HSU fibers
      was inversely correlated (R = -0.83) with thin filament density and directly
      correlated (R = 0.78) with thick-to-thin filament spacing distance in a nonlinear
      fashion. These data indicate that reduction in thin filament density contributes
      to an increased V0 in slow fibers. Osmotically compacting myofilaments with 5%
      dextran returned density, spacing, and specific tension and slowed V0 to near
      control levels and provided evidence for myofilament spacing modulating tension
      and V0.

PMID- 15469953
TI  - Differential regulation of voltage-gated K+ channels by oxidized and reduced
      pyridine nucleotide coenzymes.
AB  - The activity of the voltage-sensitive K+ (Kv) channels varies as a function of
      the intracellular redox state and metabolism, and several Kv channels act as
      oxygen sensors. However, the mechanisms underlying the metabolic and redox
      regulation of these channels remain unclear. In this study we investigated the
      regulation of Kv channels by pyridine nucleotides. Heterologous expression of
      Kvalpha1.5 in COS-7 cells led to the appearance of noninactivating currents.
      Inclusion of 0.1-1 mM NAD+ or 0.03-0.5 mM NADP+ in the internal solution of the
      patch pipette did not affect Kv currents. However, 0.5 and 1 mM NAD+ and 0.1 and
      0.5 mM NADP+ prevented inactivation of Kv currents in cells transfected with
      Kvalpha1.5 and Kvbeta1.3 and shifted the voltage dependence of activation to
      depolarized potentials. The Kvbeta-dependent inactivation of Kvalpha currents was
      also decreased by internal pipette perfusion of the cell with 1 mM NAD+. The
      Kvalpha1.5-Kvbeta1.3 currents were unaffected by the internal application of 0.1
      mM NADPH or 0.1 or 1 mM NADH. Excised inside-out patches from cells expressing
      Kvalpha1.5-Kvbeta1.3 showed transient single-channel activity. The mean open time
      and the open probability of these currents were increased by the inclusion of 1
      mM NAD+ in the perfusate. These results suggest that NAD(P)+ prevents Kvbeta
      mediated inactivation of Kv currents and provide a novel mechanism by which
      pyridine nucleotides could regulate specific K+ currents as a function of the
      cellular redox state [NAD(P)H-to-NAD(P)+ ratio].

PMID- 15469954
TI  - Helicobacter pylori lipopolysaccharide activates Rac1 and transcription of NADPH
      oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells.
AB  - Primary cultures of guinea pig gastric mucosal cells express NADPH oxidase 1
      (Nox1), a homolog of gp91(phox), and produce superoxide anion (O2-) at a rate of
      approximately 100 nmol.mg protein(-1).h(-1) in response to Helicobacter pylori
      (H. pylori) lipopolysaccharide (LPS) from virulent type I strains. The
      upregulated O2- production also enhances H. pylori LPS-stimulated tumor necrosis
      factor-alpha or cyclooxygenase-2 mRNA expression, which suggests a potential role
      for Nox1 in the pathogenesis of H. pylori-associated diseases. The H. pylori LPS
      stimulated O2- production in cultured gastric mucosal cells was inhibited by
      actinomycin D as well as cycloheximide, suggesting that the induction is
      regulated at the transcriptional level. The LPS treatment not only increased the
      Nox1 mRNA to a greater extent but also induced expression of the message
      encoding, Nox-organizing protein 1 (NOXO1), a novel p47phox homolog required for
      Nox1 activity. In addition, H. pylori LPS activated Rac1; i.e., it converted Rac1
      to the GTP-bound state. A phosphoinositide 3-kinase inhibitor, LY-294002, blocked
      H. pylori LPS-induced Rac1 activation and O2- generation without interfering with
      the expression of Nox1 and NOXO1 mRNA. O2- production inhibited by LY-294002 was
      completely restored by transfection of an adenoviral vector encoding a
      constitutively active Rac1 but not an inactive Rac1 or a constitutively active
      Cdc42. These findings indicate that Rac1 plays a crucial role in Nox1 activation.
      Thus the H. pylori LPS-stimulated O2- production in gastric mucosal cells appears
      to require two distinct events: 1) transcriptional upregulation of Nox1 and NOXO1
      and 2) activation of Rac1.

PMID- 15469955
TI  - Are second messengers crucial for opening the pore associated with P2X7 receptor?
AB  - Stimulation of the P2X7 receptor by ATP induces cell membrane depolarization,
      increase in intracellular Ca2+ concentration, and, in most cases,
      permeabilization of the cell membrane to molecules up to 900 Da. After the
      activation of P2X7, at least two phenomena occur: the opening of low-conductance
      (8 pS) cationic channels and pore formation. At least two conflicting hypotheses
      have been postulated to reconcile these findings: 1) the P2X7 pore is formed as a
      result of gradual permeability increase (dilation) of cationic channels, and 2)
      the P2X7 pore represents a distinct channel, possibly activated by a second
      messenger and not directly by extracellular nucleotides. In this study, we
      investigated whether second messengers are necessary to open the pore associated
      with the P2X7 receptor in cells that expressed the pore activity by using the
      patch-clamp technique in whole cell and cell-attached configurations in
      conjunction with fluorescent imaging. In peritoneal macrophages and 2BH4 cells,
      we detected permeabilization and single-channel currents in the cell-attached
      configuration when ATP was applied outside the membrane patch in a condition in
      which oxidized ATP and Lucifer yellow were maintained within the pipette. Our
      data support Ca2+ as a second messenger associated with pore formation because
      the permeabilization depended on the presence of intracellular Ca2+ and was
      blocked by BAPTA-AM. In addition, MAPK inhibitors (SB-203580 and PD-98059)
      blocked the permeabilization and single-channel currents in these cells. Together
      our data indicate that the P2X7 pore depends on second messengers such as Ca2+
      and MAP kinases.

PMID- 15469956
TI  - Ciglitizone inhibits cell proliferation in human uterine leiomyoma via activation
      of store-operated Ca2+ channels.
AB  - This study investigated the acute effects of a peroxisome proliferator-activated
      receptor (PPAR)-gamma ligand, ciglitizone, on cell proliferation and
      intracellular Ca2+ signaling in human normal myometrium and uterine leiomyoma.
      Changes in intracellular Ca2+ concentration ([Ca2+]i) were measured with fura-2
      AM, and cellular viabilities were determined by viable cell count and 3-(4,5
      dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction assay.
      Ciglitizone (100 microM) induced greater inhibition of cell proliferation in
      uterine leiomyoma than in myometrium. Ciglitizone also dose-dependently increased
      [Ca2+]i in both myometrium and uterine leiomyoma; these [Ca2+]i increases were
      inhibited by PPAR-gamma antagonists and raloxifene. Ciglitizone-induced [Ca2+]i
      increase showed only an initial peak in normal myometrial cells, whereas in
      uterine leiomyoma there was a second sustained [Ca2+]i increase as well. The
      initial [Ca2+]i increase in both myometrium and uterine leiomyoma resulted from
      the release of Ca2+ by the sarcoplasmic reticulum via activation of ryanodine
      receptors. The second [Ca2+]i increase was observed only in uterine leiomyoma
      because of a Ca2+ influx via an activation of store-operated Ca2+ channels
      (SOCCs). Cell proliferation was inhibited and secondary [Ca2+]i increase in
      uterine leiomyoma was attenuated by cotreatment of ciglitizone with a SOCC
      blocker, lanthanum. The results suggest that ciglitizone inhibits cell
      proliferation and increases [Ca2+]i through the activation of SOCCs, especially
      in human uterine leiomyoma.

PMID- 15469957
TI  - Oxidized linoleic acid regulates expression and shedding of syndecan-4.
AB  - Syndecan-4, a heparan sulfate proteoglycan that is widely expressed in the
      vascular wall and as a cell surface receptor, modulates events relevant to acute
      tissue repair, including cell migration and proliferation, cell-substrate
      interactions, and matrix remodeling. While syndecan-4 expression is regulated in
      response to acute vascular wall injury, its regulation under chronic
      proatherogenic conditions such as those characterized by prolonged exposure to
      oxidized lipids has not been defined. In this investigation, arterial smooth
      muscle cells were treated with 13-hydroperoxy-9,11-octadecadienoic acid (HPODE)
      and 13-hydroperoxy-10,12-octadecadienoic acid, oxidized products of linoleic
      acid, which is the major oxidizable fatty acid in LDL. Both oxidized fatty acids
      induced a dose-dependent, rapid upregulation of syndecan-4 mRNA expression that
      was not attenuated by cycloheximide. This response was inhibited by pretreatment
      with N-acetylcysteine, catalase, or MEK1/2 inhibitors, but not by curcumin or
      lactacystin, known inhibitors of NF-kappaB. These data suggest that oxidized
      linoleic acid induces syndecan-4 mRNA expression through the initial generation
      of intracellular hydrogen peroxide with subsequent activation of the
      extracellular signal-regulated kinase signaling pathway via MEK1/2. Notably, the
      HPODE-induced enhancement of syndecan-4 mRNA was accompanied by accelerated
      shedding of syndecan-4. In principle, alterations in both the cell surface
      expression and shedding of syndecan-4 may augment a variety of proatherogenic
      events that occur in response to oxidized lipids.

PMID- 15469958
TI  - Dopamine enhances spatiotemporal spread of activity in rat prefrontal cortex.
AB  - Dopaminergic modulation of prefrontal cortex (PFC) is important for neuronal
      integration in this brain region known to be involved in cognition and working
      memory. Because of the complexity and heterogeneity of the effect of dopamine on
      synaptic transmission across layers of the neocortex, dopamine's net effect on
      local circuits in PFC is difficult to predict. We have combined whole cell patch
      clamp recording and voltage-sensitive dye imaging to examine the effect of
      dopamine on the excitability of local excitatory circuits in rat PFC in vitro.
      Whole cell voltage-clamp recording from visually identified layer II/III
      pyramidal neurons in rat brain slices revealed that, in the presence of
      bicuculline (10 microM), bath-applied dopamine (30-60 microM) increased the
      amplitude of excitatory postsynaptic currents (EPSCs) evoked by weak
      intracortical stimulus. The effect was mimicked by the selective D1 receptor
      agonist SKF 81297 (1 microM). Increasing stimulation resulted in epileptiform
      discharges. SKF 81297 (1 microM) significantly lowered the threshold stimulus
      required for generating epileptiform discharges to 83% of control. In the imaging
      experiments, bath application of dopamine or SKF 81297 enhanced the
      spatiotemporal spread of activity in response to weak stimulation and previously
      subthreshold stimulation resulted in epileptiform activity that spread across the
      whole cortex. These effects could be blocked by the selective D1 receptor
      antagonist SCH 23390 (10 microM) but not by the D2 receptor antagonist
      eticlopride (5 microM). These results indicate that dopamine, by a D1 receptor
      mediated mechanism, enhances spatiotemporal spread of synaptic activity and
      lowers the threshold for epileptiform activity in local excitatory circuits
      within PFC.

PMID- 15469959
TI  - Temporal interactions of air-puff-evoked blinks and saccadic eye movements:
      insights into motor preparation.
AB  - Following the initial, sensory response to stimulus presentation, activity in
      many saccade-related burst neurons along the oculomotor neuraxis is observed as a
      gradually increasing low-frequency discharge hypothesized to encode both timing
      and metrics of the impending eye movement. When the activity reaches an
      activation threshold level, these cells discharge a high-frequency burst, inhibit
      the pontine omnipause neurons (OPNs) and trigger a high-velocity eye movement
      known as saccade. We tested whether early cessation of OPN activity, prior to
      when it ordinarily pauses, acts to effectively lower the threshold and
      prematurely trigger a movement of modified metrics and/or dynamics. Relying on
      the observation that OPN discharge ceases during not only saccades but also
      blinks, air-puffs were delivered to one eye to evoke blinks as monkeys performed
      standard oculomotor tasks. We observed a linear relationship between blink and
      saccade onsets when the blink occurred shortly after the cue to initiate the
      movement but before the average reaction time. Blinks that preceded and
      overlapped with the cue increased saccade latency. Blinks evoked during the
      overlap period of the delayed saccade task, when target location is known but a
      saccade cannot be initiated for correct performance, failed to trigger saccades
      prematurely. Furthermore, when saccade and blink execution coincided temporally,
      the peak velocity of the eye movement was attenuated, and its initial velocity
      was correlated with its latency. Despite the perturbations, saccade accuracy was
      maintained across all blink times and task types. Collectively, these results
      support the notion that temporal features of the low-frequency activity encode
      aspects of a premotor command and imply that inhibition of OPNs alone is not
      sufficient to trigger saccades.

PMID- 15469960
TI  - Shrinkage of somatosensory hand area in subjects with upper extremity dysmelia
      revealed by magnetoencephalography.
AB  - The effect of peripheral lesions on cerebral somatosensory representations is
      well studied for experimentally induced amputations and deafferentations acquired
      later in life. However, few studies have investigated the brain's capacity for
      plastic changes in congenital malformations. We studied somatosensory-evoked
      fields to electrical stimulation of the bordering fingers in 10 subjects with
      upper extremity dysmelia in comparison with 10 control subjects using a 122
      channel whole-head magnetometer. The number of developed fingers varied between
      two and four in the affected subjects. We localized finger representations in the
      primary somatosensory cortex and calculated Euclidian distances to estimate the
      size of the somatosensory hand area. Euclidian distances were significantly
      smaller in dysmelic subjects (5.7 mm) than in control subjects (11.6 mm) and were
      related to the number of the developed fingers on the contralateral hand. In
      contrast, individual finger representations were not found to be reduced. We
      suggest that the shrinkage of the somatosensory hand area might be related to the
      congenital nature of the malformation, to the smaller anatomical hand size in the
      affected subjects, and/or to use-dependent effects due to impaired hand function.

PMID- 15469961
TI  - Cortical neurons lacking KCC2 expression show impaired regulation of
      intracellular chloride.
AB  - As excitable cells, neurons experience constant changes in their membrane
      potential due to ion flux through plasma membrane channels. They maintain their
      transmembrane cation concentrations through robust Na(+)/K(+)-ATPase pump
      activity. During synaptic transmission and spread of action potentials, the
      concentration of the major anion, Cl-, is also under constant challenge from
      membrane potential changes. Moreover, intracellular Cl- is also affected by
      ligand-gated Cl- channels such as GABA(A) and glycine receptors. To regulate
      intracellular Cl- in an electrically silent manner, neurons couple the movement
      of Cl- with K+. In this study, we have used gene-targeted KCC2-/- mice to provide
      strong evidence that KCC2, the neuronal-specific K-Cl co-transporter, drives
      neuronal Cl- to low concentrations, shifting the GABA reversal potential toward
      more negative potentials, thus promoting hyperpolarizing GABA responses. Cortical
      neurons lacking KCC2, not only fail to show a developmental decrease in [Cl-]i,
      but also are unable to regulate [Cl-]i on Cl- loading or maintain [Cl]i during
      membrane depolarization. These data are consistent with the central role of KCC2
      in promoting inhibition and preventing hyperexcitability.

PMID- 15469962
TI  - Passive movements of the head do not abolish anticipatory firing properties of
      head direction cells.
AB  - Neurons in the anterior dorsal thalamic nucleus (ADN) of the rat selectively
      discharge in relation to the animal's head direction (HD) in the horizontal
      plane. Temporal analyses of cell firing properties reveal that their discharge is
      optimally correlated with the animal's future directional heading by
      approximately 24 ms. Among the hypotheses proposed to explain this property is
      that ADN HD cells are informed of future head movement via motor efference copy
      signals. One prediction of this hypothesis is that when the rat's head is moved
      passively, the anticipatory time interval (ATI) will be attenuated because the
      motor efference signal reflects only the active contribution to the movement. The
      present study tested this hypothesis by loosely restraining the animal and
      passively rotating it through the cell's preferred direction. Contrary to our
      prediction, we found that ATI values did not decrease during passive movement but
      in fact increased significantly. HD cells in the postsubiculum did not show the
      same effect, suggesting independence between the two sites with respect to
      anticipatory firing. We conclude that it is unlikely that a motor efference copy
      signal alone is responsible for generating anticipatory firing in ADN HD cells.

PMID- 15469963
TI  - Modeling neuromuscular modulation in Aplysia. III. Interaction of central motor
      commands and peripheral modulatory state for optimal behavior.
AB  - Recent work in computational neuroethology has emphasized that "the brain has a
      body": successful adaptive behavior is not simply commanded by the nervous
      system, but emerges from interactions of nervous system, body, and environment.
      Here we continue our study of these issues in the accessory radula closer (ARC)
      neuromuscular system of Aplysia. The ARC muscle participates in the animal's
      feeding behaviors, a set of cyclical, rhythmic behaviors driven by a central
      pattern generator (CPG). Patterned firing of the ARC muscle's two motor neurons,
      B15 and B16, releases not only ACh to elicit the muscle's contractions but also
      peptide neuromodulators that then shape the contractions through a complex
      network of actions on the muscle. These actions are dynamically complex: some are
      fast, but some are slow, so that they are temporally uncoupled from the motor
      neuron firing pattern in the current cycle. Under these circumstances, how can
      the nervous system, through just the narrow channel of the firing patterns of the
      motor neurons, control the contractions, movements, and behavior in the
      periphery? In two earlier papers, we developed a realistic mathematical model of
      the B15/B16-ARC neuromuscular system and its modulation. Here we use this model
      to study the functional performance of the system in a realistic behavioral task.
      We run the model with two kinds of inputs: a simple set of regular motor neuron
      firing patterns that allows us to examine the entire space of patterns, and the
      real firing patterns of B15 and B16 previously recorded in a 2 1/2-h-long meal of
      749 cycles in an intact feeding animal. These real patterns are extremely
      irregular. Our main conclusions are the following. 1) The modulation in the
      periphery is necessary for superior functional performance. 2) The components of
      the modulatory network interact in nonlinear, context- and task-dependent
      combinations for best performance overall, although not necessarily in any
      particular cycle. 3) Both the fast and the slow dynamics of the modulatory state
      make important contributions. 4) The nervous system controls different components
      of the periphery to different degrees. To some extent the periphery operates
      semiautonomously. However, the structure of the peripheral modulatory network
      ensures robust performance under all circumstances, even with the irregular motor
      neuron firing patterns and even when the parameters of the functional task are
      randomly varied from cycle to cycle to simulate a variable feeding environment.
      In the variable environment, regular firing patterns, which are fine-tuned to one
      particular task, fail to provide robust performance. We propose that the CPG
      generates the irregular firing patterns, which nevertheless are guaranteed to
      give robust performance overall through the actions of the peripheral modulatory
      network, as part of a trial-and-error feeding strategy in a variable, uncertain
      environment.

PMID- 15469964
TI  - Loss of cyclin-dependent kinase inhibitors produces adipocyte hyperplasia and
      obesity.
AB  - Adipocyte hyperplasia is characteristic of some forms of human obesity, but the
      role of adipocyte number in obesity and how normal adipocyte number is
      established are unclear. Preadipocytes proliferate and then differentiate to
      become mitotically quiescent adipocytes. This involves exit from the cell cycle,
      a process regulated by cell cycle inhibitors such as the cyclin-dependent kinase
      inhibitors (CDKIs) p27 and p21. 3T3-L1 preadipocytes show marked changes in p27
      and p21 during differentiation, suggesting CDKIs may regulate establishment of
      adipocyte number in vivo. To study the role of these CDKIs in adipogenesis, we
      analyzed adult p27 knockout (p27KO), p21 knockout (p21KO), p27/p21 double
      knockout (DBKO), and wild-type (WT) mice. Adult DBKO mice weighed 100% more and
      had fourfold increases in body fat percentage compared with WT. Fat pad weights
      were increased 80, 90, and 500% in p27KO, p21KO, and DBKO mice, respectively,
      compared with WT. Adipocyte numbers of p27KO, p21KO, and DBKO mice were 1.9-, 1.7
      , and 6.1-fold, respectively, that of WT; adipocyte size was not increased. DBKO
      mice showed glucose intolerance, insulin insensitivity, hepatic steatosis and
      dyslipidemia; gradations of these effects occurred in p27KO and p21KO mice. In
      conclusion, p27KO and p21KO mice are obese because of adipocyte hyperplasia, and
      DBKO mice have further increases in obesity and adipocyte hyperplasia, indicating
      that their functions in establishing adipocyte number are not redundant. p27 and
      p21 are major regulators of adipocyte number in vivo, and knockouts lacking one
      or both of these proteins provide models for producing adipocyte hyperplasia and
      understanding its metabolic consequences.

PMID- 15469965
TI  - Epigenetic reprogramming of UDP-N-acetylglucosamine 2-epimerase/N
      acetylmannosamine kinase (GNE) in HIV-1-infected CEM T cells.
AB  - Sialylated glycoconjugates mediate several key lymphocyte functions. We
      previously reported that hyposialylation occurred in latently HIV-1-infected CEM
      T cells, despite the fully preserved catalytic activity of several
      sialyltransferases. We show now that these cells are affected by a down
      regulation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
      (GNE), which leads to a dramatic decrease in the synthesis of CMP-sialic acid,
      the donor substrate of all sialyltransferases. The GNE gene promoter was found to
      be located in a CpG island with several regulatory motifs CREB, SP1, and AP-2. De
      novo hypermethylation of this promoter was observed in HIV-1-infected CEM cells.
      This phenomenon might explain some immunological disorders that persist in
      infected individuals despite long-term therapeutically controlled viral
      replication. Indeed, an overall decrease in sialic acid engraftment can affect
      glycoproteins, notably those in which the sialylation status is crucial to ensure
      homing, recirculation, and survival of lymphocytes.

PMID- 15469966
TI  - Tyrosine phosphorylation of the LDL receptor-related protein (LRP) and activation
      of the ERK pathway are required for connective tissue growth factor to potentiate
      myofibroblast differentiation.
AB  - Renal myofibroblasts play a crucial role in the accumulation of excess
      extracellular matrix during renal fibrosis. Both transforming growth factor-beta1
      (TGFbeta1) and connective tissue growth factor (CTGF) are important profibrotic
      growth factors, which interact in the pathogenesis of fibrosis. In this study, we
      demonstrate that CTGF alone has no influence on myofibroblast transformation and
      fibronectin secretion in kidney interstitial fibroblasts, whereas incubation of
      CTGF in combination with TGFbeta1 enhanced TGFbeta1 responses, including
      myofibroblast activation, de novo expression of alpha-SMA, and extracellular
      accumulation of fibronectin. CTGF induced tryrosine phosphorylation of the
      cytoplasmic domain of the low-density lipoprotein receptor-associated protein
      (LRP) in fibroblasts, and the LRP-antagonist, receptor-associated protein (RAP)
      inhibited CTGF-induced tryrosine phosphorylation of LRP. Inhibition of LRP
      signaling reduced CTGF-mediated synergistic induction of alpha-SMA protein.
      Furthermore, the potentiating action of CTGF was neither dependent on modulation
      of TGFbeta1-induced Smad2 phosphorylation and its association with Smad4, nor did
      it result from nuclear accumulation of activated Smad2. When TGFbeta1-pretreated
      fibroblasts were incubated with CTGF, activation of ERK1/2 MAPK signaling was
      observed. Inhibition of ERK activation by the MEK1 inhibitor PD98059 was
      associated with a reduction of CTGF-promoted alpha-SMA protein expression. Our in
      vitro studies provide evidence that CTGF potentiates TGFbeta1-mediated
      myofibroblast differentiation and activates differentiated myofibroblasts.

PMID- 15469967
TI  - Fat facets and Liquid facets promote Delta endocytosis and Delta signaling in the
      signaling cells.
AB  - Endocytosis modulates the Notch signaling pathway in both the signaling and
      receiving cells. One recent hypothesis is that endocytosis of the ligand Delta by
      the signaling cells is essential for Notch activation in the receiving cells.
      Here, we present evidence in strong support of this model. We show that in the
      developing Drosophila eye Fat facets (Faf), a deubiquitinating enzyme, and its
      substrate Liquid facets (Lqf), an endocytic epsin, promote Delta internalization
      and Delta signaling in the signaling cells. We demonstrate that while Lqf is
      necessary for three different Notch/Delta signaling events at the morphogenetic
      furrow, Faf is essential only for one: Delta signaling by photoreceptor
      precluster cells, which prevents recruitment of ectopic neurons. In addition, we
      show that the ubiquitin-ligase Neuralized (Neur), which ubiquitinates Delta,
      functions in the signaling cells with Faf and Lqf. The results presented bolster
      one model for Neur function in which Neur enhances Delta signaling by stimulating
      Delta internalization in the signaling cells. We propose that Faf plays a role
      similar to that of Neur in the Delta signaling cells. By deubiquitinating Lqf,
      which enhances the efficiency of Delta internalization, Faf stimulates Delta
      signaling.

PMID- 15469969
TI  - Morphogenesis in the absence of integrins: mutation of both Drosophila beta
      subunits prevents midgut migration.
AB  - Two integrin beta subunits are encoded in the Drosophila genome. The betaPS
      subunit is widely expressed and heterodimers containing this subunit are required
      for many developmental processes. The second betasubunit, betanu, is a divergent
      integrin expressed primarily in the midgut endoderm. To elucidate its function,
      we generated null mutations in the gene encoding betanu. We find that betanu is
      not required for viability or fertility, and overall the mutant flies are normal
      in appearance. However, we could observe betanu function in the absence of
      betaPS. Consistent with its expression, removal of betanu only enhanced the
      phenotype of betaPS in the developing midgut. In embryos lacking the zygotic
      contribution of betaPS, loss of betanu resulted in enhanced separation between
      the midgut and the surrounding visceral mesoderm. In the absence of both maternal
      and zygotic betaPS, a delay in midgut migration was observed, but removing betanu
      as well blocked migration completely. These results demonstrate that the second
      beta subunit can partially compensate for loss of betaPS integrins, and that
      integrins are essential for migration of the primordial midgut cells. The two
      beta subunits mediate midgut migration by distinct mechanisms: one that requires
      talin and one that does not. Other examples of developmental cell migration, such
      as that of the primordial germ cells, occurred normally in the absence of
      integrins. Having generated the tools to eliminate integrin function completely,
      we confirm that Drosophila integrins do not control proliferation as they do in
      mammals, and have identified alphaPS3 as a heterodimeric partner for betanu.

PMID- 15469968
TI  - Id4 regulates neural progenitor proliferation and differentiation in vivo.
AB  - The mechanisms that determine whether a precursor cell re-enters the cell cycle
      or exits and differentiates are crucial in determining the types and numbers of
      cells that constitute a particular organ. Here, we report that Id4 is required
      for normal brain size, and regulates lateral expansion of the proliferative zone
      in the developing cortex and hippocampus. In its absence, proliferation of stem
      cells in the ventricular zone (VZ) is compromised. In early cortical progenitors,
      Id4 is required for the normal G1-S transition. By contrast, at later ages,
      ectopically positioned proliferating cells are found in the mantle zone of the
      Id4-/- cortex. These observations, together with evidence for the premature
      differentiation of early cortical stem cells, indicate that Id4 has a unique and
      complex function in regulating neural stem cell proliferation and
      differentiation.

PMID- 15469970
TI  - FGF and PI3 kinase signaling pathways antagonistically modulate sex muscle
      differentiation in C. elegans.
AB  - Myogenesis in vertebrate myocytes is promoted by activation of the phosphatidyl
      inositol 3'-kinase (PI3 kinase) pathway and inhibited by fibroblast growth factor
      (FGF) signaling. We show that hyperactivation of the Caenorhabditis elegans FGF
      receptor, EGL-15, similarly inhibits the differentiation of the hermaphrodite sex
      muscles. Activation of the PI3 kinase signaling pathway can partially suppress
      this differentiation defect, mimicking the antagonistic relationship between
      these two pathways known to influence vertebrate myogenesis. When ectopically
      expressed in body wall muscle precursor cells, hyperactivated EGL-15 can also
      interfere with the proper development of the body wall musculature.
      Hyperactivation of EGL-15 has also revealed additional effects on a number of
      fundamental processes within the postembryonic muscle lineage, such as cell
      division polarity. These studies provide important in vivo insights into the
      contribution of FGF signaling events to myogenesis.

PMID- 15469971
TI  - Mice expressing a dominant-negative Ret mutation phenocopy human Hirschsprung
      disease and delineate a direct role of Ret in spermatogenesis.
AB  - The Ret receptor tyrosine kinase mediates physiological signals of glial cell
      line-derived neurotrophic factor (GDNF) family ligands (GFLs) and is essential
      for postnatal survival in mice. It is implicated in a number of human diseases
      and developmental abnormalities. Here, we describe our analyses of mice
      expressing a Ret mutant (RetDN) with diminished kinase activity that inhibits
      wild-type Ret activity, including its activation of AKT. All RetDN/+ mice died by
      1 month of age and had distal intestinal aganglionosis reminiscent of
      Hirschsprung disease (HSCR) in humans. The RetDN/+ proximal small intestine also
      had severe hypoganglionosis and reduction in nerve fiber density, suggesting a
      potential mechanism for the continued gastric dysmotility in postsurgical HSCR
      patients. Unlike Ret-null mice, which have abnormalities in the parasympathetic
      and sympathetic nervous systems, the RetDN/+ mice only had defects in the
      parasympathetic nervous system. A small proportion of RetDN/+ mice had renal
      agenesis, and the remainder had hypoplastic kidneys and developed tubulocystic
      abnormalities postnatally. Postnatal analyses of the testes revealed a decreased
      number of germ cells, degenerating seminiferous tubules, maturation arrest and
      apoptosis, indicating a crucial role for Ret in early spermatogenesis.

PMID- 15469972
TI  - Developmental potential of defined neural progenitors derived from mouse
      embryonic stem cells.
AB  - The developmental potential of a uniform population of neural progenitors was
      tested by implanting them into chick embryos. These cells were generated from
      retinoic acid-treated mouse embryonic stem (ES) cells, and were used to replace a
      segment of the neural tube. At the time of implantation, the progenitors
      expressed markers defining them as Pax6-positive radial glial (RG) cells, which
      have recently been shown to generate most pyramidal neurons in the developing
      cerebral cortex. Six days after implantation, the progenitors generated large
      numbers of neurons in the spinal cord, and differentiated into interneurons and
      motoneurons at appropriate locations. They also colonized the host dorsal root
      ganglia (DRG) and differentiated into neurons, but, unlike stem cell-derived
      motoneurons, they failed to elongate axons out of the DRG. In addition, they
      neither expressed the DRG marker Brn3a nor the Trk neurotrophin receptors.
      Control experiments with untreated ES cells indicated that when colonizing the
      DRG, these cells did elongate axons and expressed Brn3a, as well as Trk
      receptors. Our results thus indicate that ES cell-derived progenitors with RG
      characteristics generate neurons in the spinal cord and the DRG. They are able to
      respond appropriately to local cues in the spinal cord, but not in the DRG,
      indicating that they are restricted in their developmental potential.

PMID- 15469973
TI  - Specification of Drosophila motoneuron identity by the combinatorial action of
      POU and LIM-HD factors.
AB  - In both vertebrates and invertebrates, members of the LIM-homeodomain (LIM-HD)
      family of transcription factors act in combinatorial codes to specify motoneuron
      subclass identities. In the developing Drosophila embryo, the LIM-HD factors
      Islet (Tailup) and Lim3, specify the set of motoneuron subclasses that innervate
      ventral muscle targets. However, as several subclasses express both Islet and
      Lim3, this combinatorial code alone cannot explain how these motoneuron groups
      are further differentiated. To identify additional factors that may act to refine
      this LIM-HD code, we have analyzed the expression of POU genes in the Drosophila
      embryonic nerve cord. We find that the class III POU protein, Drifter (Ventral
      veinless), is co-expressed with Islet and Lim3 specifically in the ISNb
      motoneuron subclass. Loss-of-function and misexpression studies demonstrate that
      the LIM-HD combinatorial code requires Drifter to confer target specificity
      between the ISNb and TN motoneuron subclasses. To begin to elucidate molecules
      downstream of the LIM-HD code, we examined the involvement of the Beaten path
      (Beat) family of immunoglobulin-containing cell-adhesion molecules. We find that
      beat Ic genetically interacts with islet and Lim3 in the TN motoneuron subclass
      and can also rescue the TN fasciculation defects observed in islet and Lim3
      mutants. These results suggest that in the TN motoneuron context, Islet and Lim3
      may specify axon target selection through the actions of IgSF call-adhesion
      molecules.

PMID- 15469974
TI  - Drosophila Epsin mediates a select endocytic pathway that DSL ligands must enter
      to activate Notch.
AB  - Recent findings suggest that Delta/Serrate/Lag2 (DSL) signals activate Notch by
      an unprecedented mechanism that requires the ligands to be endocytosed in signal
      sending cells to activate the receptor in signal-receiving cells. Here, we show
      that cells devoid of Epsin, a conserved adaptor protein for Clathrin-mediated
      endocytosis, behave normally except that they cannot send DSL signals.
      Surprisingly, we find that Epsin is not required for bulk endocytosis of DSL
      proteins. Instead, Epsin appears to be essential for targeting DSL proteins to a
      special endocytic pathway that they must enter to acquire signaling activity. We
      present evidence that DSL proteins must be mono-ubiquitinated to be targeted by
      Epsin to this pathway. Furthermore, we show that the requirements for both Epsin
      and mono-ubiquitination can be bypassed by introducing the internalization signal
      that mediates endocytosis and recycling of the Low Density Lipoprotein (LDL)
      receptor. We propose that Epsin is essential for DSL signaling because it targets
      mono-ubiquitinated DSL proteins to an endocytic recycling compartment that they
      must enter to be converted into active ligands. Alternatively Epsin may be
      required to target mono-ubiquitinated DSL proteins to a particular subclass of
      coated pits that have special properties essential for Notch activation.

PMID- 15469975
TI  - accordion, a zebrafish behavioral mutant, has a muscle relaxation defect due to a
      mutation in the ATPase Ca2+ pump SERCA1.
AB  - When wild-type zebrafish embryos are touched at 24 hours post-fertilization
      (hpf), they typically perform two rapid alternating coils of the tail. By
      contrast, accordion (acc) mutants fail to coil their tails normally but contract
      the bilateral trunk muscles simultaneously to shorten the trunk, resulting in a
      pronounced dorsal bend. Electrophysiological recordings from muscles showed that
      the output from the central nervous system is normal in mutants, suggesting a
      defect in muscles is responsible. In fact, relaxation in acc muscle is
      significantly slower than normal. In vivo imaging of muscle Ca2+ transients
      revealed that cytosolic Ca2+ decay was significantly slower in acc muscle. Thus,
      it appears that the mutant behavior is caused by a muscle relaxation defect due
      to the impairment of Ca2+ re-uptake. Indeed, acc mutants carry a mutation in
      atp2a1 gene that encodes the sarco(endo)plasmic reticulum Ca2+-ATPase 1 (SERCA1),
      a Ca2+ pump found in the muscle sarcoplasmic reticulum (SR) that is responsible
      for pumping Ca2+ from the cytosol back to the SR. As SERCA1 mutations in humans
      lead to Brody disease, an exercise-induced muscle relaxation disorder, zebrafish
      accordion mutants could be a useful animal model for this condition.

PMID- 15469976
TI  - Phosphatidylserine receptor is required for the engulfment of dead apoptotic
      cells and for normal embryonic development in zebrafish.
AB  - During development, the role of the phosphatidylserine receptor (PSR) in the
      removal of apoptotic cells that have died is poorly understood. We have
      investigated this role of PSR in developing zebrafish. Programmed cell death
      began during the shield stage, with dead cells being engulfed by a neighboring
      cell that showed a normal-looking nucleus and the nuclear condensation multi
      micronuclei of an apoptotic cell. The zebrafish PSR engulfing receptor was cloned
      (zfpsr), and its nucleotide sequence was compared with corresponding sequences in
      Drosophila melanogaster (76% identity), human (74%), mouse (72%) and
      Caenorhabditis elegans (60%). The PSR receptor contained a jmjC domain (residues
      143-206) that is a member of the cupin metalloenzyme superfamily, but in this
      case serves an as yet unknown function(s). psr knockdown by a PSR morpholino
      oligonucleotide led to accumulation of a large number of dead apoptotic cells in
      whole early embryo. These cells interfered with embryonic cell migration. In
      addition, normal development of the somite, brain, heart and notochord was
      sequentially disrupted up to 24 hours post-fertilization. Development could be
      rescued in defective embryos by injecting psr mRNA. These results are consistent
      with a PSR-dependent system in zebrafish embryos that engulfs apoptotic cells
      mediated by PSR-phagocytes during development, with the system assuming an
      important role in the normal development of tissues such as the brain, heart,
      notochord and somite.

PMID- 15469977
TI  - Skeletal defects in ringelschwanz mutant mice reveal that Lrp6 is required for
      proper somitogenesis and osteogenesis.
AB  - Here, we present evidence that Lrp6, a coreceptor for Wnt ligands, is required
      for the normal formation of somites and bones. By positional cloning, we
      demonstrate that a novel spontaneous mutation ringelschwanz (rs) in the mouse is
      caused by a point mutation in Lrp6, leading to an amino acid substitution of
      tryptophan for the evolutionarily conserved residue arginine at codon 886
      (R886W). We show that rs is a hypomorphic Lrp6 allele by a genetic
      complementation test with Lrp6-null mice, and that the mutated protein cannot
      efficiently transduce signals through the Wnt/beta-catenin pathway. Homozygous rs
      mice, many of which are remarkably viable, exhibit a combination of multiple Wnt
      deficient phenotypes, including dysmorphologies of the axial skeleton, digits and
      the neural tube. The establishment of the anteroposterior somite compartments,
      the epithelialization of nascent somites, and the formation of segment borders
      are disturbed in rs mutants, leading to a characteristic form of vertebral
      malformations, similar to dysmorphologies in individuals suffering from
      spondylocostal dysostosis. Marker expression study suggests that Lrp6 is required
      for the crosstalk between the Wnt and notch-delta signaling pathways during
      somitogenesis. Furthermore, the Lrp6 dysfunction in rs leads to delayed
      ossification at birth and to a low bone mass phenotype in adults. Together, we
      propose that Lrp6 is one of the key genetic components for the pathogenesis of
      vertebral segmentation defects and of osteoporosis in humans.

PMID- 15469978
TI  - Tbx1 regulates fibroblast growth factors in the anterior heart field through a
      reinforcing autoregulatory loop involving forkhead transcription factors.
AB  - Birth defects, which occur in one out of 20 live births, often affect multiple
      organs that have common developmental origins. Human and mouse studies indicate
      that haploinsufficiency of the transcription factor TBX1 disrupts pharyngeal arch
      development, resulting in the cardiac and craniofacial features associated with
      microdeletion of 22q11 (del22q11), the most frequent human deletion syndrome.
      Here, we have generated an allelic series of Tbx1 deficiency that reveals a lower
      critical threshold for Tbx1 activity in the cardiac outflow tract compared with
      other pharyngeal arch derivatives, including the palatal bones. Mice hypomorphic
      for Tbx1 failed to activate expression of the forkhead transcription factor Foxa2
      in the pharyngeal mesoderm, which contains cardiac outflow precursors derived
      from the anterior heart field. We identified a Fox-binding site upstream of Tbx1
      that interacted with Foxa2 and was necessary for pharyngeal mesoderm expression
      of Tbx1, revealing an autoregulatory loop that may explain the increased cardiac
      sensitivity to Tbx1 dose. Downstream of Tbx1, we found a fibroblast growth factor
      8 (Fgf8) enhancer that was dependent on Tbx1 in vivo for regulating expression in
      the cardiac outflow tract, but not in pharyngeal arches. Consistent with its role
      in regulating cardiac outflow tract cells Tbx1 gain of function resulted in
      expansion of the cardiac outflow tract segment derived from the anterior heart
      field as marked by Fgf10. These findings reveal a Tbx1-dependent transcriptional
      and signaling network in the cardiac outflow tract that renders mouse
      cardiovascular development more susceptible than craniofacial development to a
      reduction in Tbx1 dose, similar to humans with del22q11.

PMID- 15469979
TI  - Muscle reconstitution by muscle satellite cell descendants with stem cell-like
      properties.
AB  - Recent studies have demonstrated that a distinct subpopulation with stem cell
      like characteristics in myoblast culture is responsible for new muscle fiber
      formation after intramuscular transplantation. The identification and isolation
      of stem-like cells would have significant implications for successful myogenic
      cell transfer therapy in human muscle disorders. Using a clonal culture system
      for mouse muscle satellite cells, we have identified two cell types, designated
      'round cells' and 'thick cells', in clones derived from single muscle satellite
      cells that have been taken from either slow or fast muscle. Clonal analysis of
      satellite cells revealed that the round cells are immediate descendants of
      quiescent satellite cells in adult muscle. In single-myofiber culture, round
      cells first formed colonies and then generated progeny, thick cells, that
      underwent both myogenic and osteogenic terminal differentiation under the
      appropriate culture conditions. Thick cells, but not round cells, responded to
      terminal differentiation-inducing signals. Round cells express Pax7, a specific
      marker of satellite cells, at high levels. Myogenic cell transfer experiments
      showed that round cells reconstitute myofibers more efficiently than thick cells.
      Furthermore, round cells restored dystrophin in myofibers of mdx nude mice, even
      when as few as 5000 cells were transferred into the gastrocnemius muscle. These
      results suggest that round cells are satellite-cell descendants with stem cell
      like characteristics and represent a useful source of donor cells to improve
      muscle regeneration.

PMID- 15469980
TI  - Signaling through BMP type 1 receptors is required for development of interneuron
      cell types in the dorsal spinal cord.
AB  - During spinal cord development, distinct classes of interneurons arise at
      stereotypical locations along the dorsoventral axis. In this paper, we
      demonstrate that signaling through bone morphogenetic protein (BMP) type 1
      receptors is required for the formation of two populations of commissural
      neurons, DI1 and DI2, that arise within the dorsal neural tube. We have generated
      a double knockout of both BMP type 1 receptors, Bmpr1a and Bmpr1b, in the neural
      tube. These double knockout mice demonstrate a complete loss of D1 progenitor
      cells, as evidenced by loss of Math1 expression, and the subsequent failure to
      form differentiated DI1 interneurons. Furthermore, the DI2 interneuron population
      is profoundly reduced. The loss of these populations of cells results in a dorsal
      shift of the dorsal cell populations, DI3 and DI4. Other dorsal interneuron
      populations, DI5 and DI6, and ventral neurons appear unaffected by the loss of
      BMP signaling. The Bmpr double knockout animals demonstrate a reduction in the
      expression of Wnt and Id family members, suggesting that BMP signaling regulates
      expression of these factors in spinal cord development. These results provide
      genetic evidence that BMP signaling is crucial for the development of dorsal
      neuronal cell types.

PMID- 15469981
TI  - Direct visualization of microtubule flux during metaphase and anaphase in crane
      fly spermatocytes.
AB  - Microtubule flux in spindles of insect spermatocytes, long-used models for
      studies on chromosome behavior during meiosis, was revealed after iontophoretic
      microinjection of rhodamine-conjugated (rh)-tubulin and fluorescent speckle
      microscopy. In time-lapse movies of crane-fly spermtocytes, fluorescent speckles
      generated when rh-tubulin incorporated at microtubule plus ends moved poleward
      through each half-spindle and then were lost from microtubule minus ends at the
      spindle poles. The average poleward velocity of approximately 0.7 microm/min for
      speckles within kinetochore microtubules at metaphase increased during anaphase
      to approximately 0.9 microm/min. Segregating half-bivalents had an average
      poleward velocity of approximately 0.5 microm/min, about half that of speckles
      within shortening kinetochore fibers. When injected during anaphase, rhtubulin
      was incorporated at kinetochores, and kinetochore fiber fluorescence spread
      poleward as anaphase progressed. The results show that tubulin subunits are added
      to the plus end of kinetochore microtubules and are removed from their minus ends
      at the poles, all while attached chromosomes move poleward during anaphase A. The
      results cannot be explained by a Pac-man model, in which 1) kinetochore-based,
      minus end-directed motors generate poleward forces for anaphase A and 2)
      kinetochore microtubules shorten at their plus ends. Rather, in these cells,
      kinetochore fiber shortening during anaphase A occurs exclusively at the minus
      ends of kinetochore microtubules.

PMID- 15469982
TI  - IC138 is a WD-repeat dynein intermediate chain required for light chain assembly
      and regulation of flagellar bending.
AB  - Increased phosphorylation of dynein IC IC138 correlates with decreases in
      flagellar microtubule sliding and phototaxis defects. To test the hypothesis that
      regulation of IC138 phosphorylation controls flagellar bending, we cloned the
      IC138 gene. IC138 encodes a novel protein with a calculated mass of 111 kDa and
      is predicted to form seven WD-repeats at the C terminus. IC138 maps near the BOP5
      locus, and bop5-1 contains a point mutation resulting in a truncated IC138
      lacking the C terminus, including the seventh WD-repeat. bop5-1 cells display
      wild-type flagellar beat frequency but swim slower than wild-type cells,
      suggesting that bop5-1 is altered in its ability to control flagellar waveform.
      Swimming speed is rescued in bop5-1 transformants containing the wild-type IC138,
      confirming that BOP5 encodes IC138. With the exception of the roadblock-related
      light chain, LC7b, all the other known components of the I1 complex, including
      the truncated IC138, are assembled in bop5-1 axonemes. Thus, the bop5-1 motility
      phenotype reveals a role for IC138 and LC7b in the control of flagellar bending.
      IC138 is hyperphosphorylated in paralyzed flagellar mutants lacking radial spoke
      and central pair components, further indicating a role for the radial spokes and
      central pair apparatus in control of IC138 phosphorylation and regulation of
      flagellar waveform.

PMID- 15469983
TI  - NVL2 is a nucleolar AAA-ATPase that interacts with ribosomal protein L5 through
      its nucleolar localization sequence.
AB  - NVL (nuclear VCP-like protein), a member of the AAA-ATPase family, is known to
      exist in two forms with N-terminal extensions of different lengths in mammalian
      cells. Here, we show that they are localized differently in the nucleus; NVL2,
      the major species, is mainly present in the nucleolus, whereas NVL1 is
      nucleoplasmic. Mutational analysis demonstrated the presence of two nuclear
      localization signals in NVL2, one of which is shared with NVL1. In addition, a
      nucleolar localization signal was found to exist in the N-terminal extra region
      of NVL2. The nucleolar localization signal is critical for interaction with
      ribosomal protein L5, which was identified as a specific interaction partner of
      NVL2 on yeast two-hybrid screening. The interaction of NVL2 with L5 is ATP
      dependent and likely contributes to the nucleolar translocation of NVL2. The
      physiological implication of this interaction was suggested by the finding that a
      dominant negative NVL2 mutant inhibits ribosome biosynthesis, which is known to
      take place in the nucleolus.

PMID- 15469984
TI  - Plk1 regulates activation of the anaphase promoting complex by phosphorylating
      and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1.
AB  - Progression through mitosis requires activation of cyclin B/Cdk1 and its
      downstream targets, including Polo-like kinase and the anaphase-promoting complex
      (APC), the ubiquitin ligase directing degradation of cyclins A and B. Recent
      evidence shows that APC activation requires destruction of the APC inhibitor
      Emi1. In prophase, phosphorylation of Emi1 generates a D-pS-G-X-X-pS degron to
      recruit the SCF(betaTrCP) ubiquitin ligase, causing Emi1 destruction and allowing
      progression beyond prometaphase, but the kinases directing this phosphorylation
      remain undefined. We show here that the polo-like kinase Plk1 is strictly
      required for Emi1 destruction and that overexpression of Plk1 is sufficient to
      trigger Emi1 destruction. Plk1 stimulates Emi1 phosphorylation, betaTrCP binding,
      and ubiquitination in vitro and cyclin B/Cdk1 enhances these effects. Plk1 binds
      to Emi1 in mitosis and the two proteins colocalize on the mitotic spindle poles,
      suggesting that Plk1 may spatially control Emi1 destruction. These data support
      the hypothesis that Plk1 activates the APC by directing the SCF-dependent
      destruction of Emi1 in prophase.

PMID- 15469985
TI  - Enlargeosome, an exocytic vesicle resistant to nonionic detergents, undergoes
      endocytosis via a nonacidic route.
AB  - Enlargeosomes, a new type of widely expressed cytoplasmic vesicles, undergo
      tetanus toxin-insensitive exocytosis in response to cytosolic Ca(2+)
      concentration ([Ca(2+)](i)) rises. Cell biology of enlargeosomes is still largely
      unknown. By combining immunocytochemistry (marker desmoyokin-Ahnak, d/A) to
      capacitance electrophysiology in the enlargeosome-rich, neurosecretion-defective
      clone PC12-27, we show that 1) the two responses, cell surface enlargement and
      d/A surface appearance, occur with similar kinetics and in the same low
      micromolar [Ca(2+)](i) range, no matter whether induced by photolysis of the
      caged Ca(2+) compound o-nitrophenyl EGTA or by the Ca(2+) ionophore ionomycin.
      Thus, enlargeosomes seem to account, at least in large part, for the exocytic
      processes triggered by the two stimulations. 2. The enlargeosome membranes are
      resistant to nonionic detergents but distinct from other resistant membranes,
      rich in caveolin, Thy1, and/or flotillin1. 3. Cell cholesterol depletion, which
      affects many membrane fusions, neither disrupts enlargeosomes nor affects their
      regulated exocytosis. 4. The postexocytic cell surface decline is [Ca(2+)](i)
      dependent. 5. Exocytized d/A-rich membranes are endocytized and trafficked along
      an intracellular pathway by nonacidic organelles, distinct from classical
      endosomes and lysosomes. Our data define specific aspects of enlargeosomes and
      suggest their participation, in addition to cell differentiation and repair, for
      which evidence already exists, to other physiological and pathological processes.

PMID- 15469986
TI  - Short tetracysteine tags to beta-tubulin demonstrate the significance of small
      labels for live cell imaging.
AB  - Genetically encoded tags are of fundamental importance for live cell imaging. We
      show that small tetracysteine (TetCys) tags can be highly advantageous for the
      functionality of the host protein compared with large fluorescent protein tags.
      One to three concatenated small TetCys tags as well as the large green
      fluorescent protein (GFP) were fused by integrative epitope tagging to the C
      terminus of beta-tubulin (Tub2) in the budding yeast Saccharomyces cerevisiae.
      The increasing tag size correlated with functional interference to the host
      protein. Tub2 tagged with either 1 x TetCys (10 amino acids [aa]) or 2 x TetCys
      (20 aa) was able to substitute Tub2 in haploid cells. In contrast, C-terminal
      tagging of Tub2 with 3 x TetCys (29 aa) or with GFP (244 aa) resulted in
      nonviable haploid cells. Cells expressing Tub2-1 x TetCys or Tub2-2 x TetCys were
      stained with FlAsH, which selectively binds to the TetCys-tag. The stained cells
      displayed dynamic FlAsH-labeled microtubules and low cellular background
      fluorescence. The presented approach to tag open reading frames (ORFs) at their
      native loci with very small TetCys-tags and the subsequent visualization of the
      tagged proteins in vivo can be extended in principle to any ORF in S. cerevisiae.

PMID- 15469987
TI  - Regulation of epidermal growth factor receptor degradation by heterotrimeric
      Galphas protein.
AB  - Heterotrimeric G proteins have been implicated in the regulation of membrane
      trafficking, but the mechanisms involved are not well understood. Here, we report
      that overexpression of the stimulatory G protein subunit (Galphas) promotes
      ligand-dependent degradation of epidermal growth factor (EGF) receptors and Texas
      Red EGF, and knock-down of Galphas expression by RNA interference (RNAi) delays
      receptor degradation. We also show that Galphas and its GTPase activating protein
      (GAP), RGS-PX1, interact with hepatocyte growth factor-regulated tyrosine kinase
      substrate (Hrs), a critical component of the endosomal sorting machinery. Galphas
      coimmunoprecipitates with Hrs and binds Hrs in pull-down assays. By
      immunofluorescence, exogenously expressed Galphas colocalizes with myc-Hrs and
      GFP-RGS-PX1 on early endosomes, and expression of either Hrs or RGS-PX1 increases
      the localization of Galphas on endosomes. Furthermore, knock-down of both Hrs and
      Galphas by double RNAi causes greater inhibition of EGF receptor degradation than
      knock-down of either protein alone, suggesting that Galphas and Hrs have
      cooperative effects on regulating EGF receptor degradation. These observations
      define a novel regulatory role for Galphas in EGF receptor degradation and
      provide mechanistic insights into the function of Galphas in endocytic sorting.

PMID- 15469988
TI  - Regulation of the vasopressin V2 receptor by vasopressin in polarized renal
      collecting duct cells.
AB  - Binding of arginine-vasopressin (AVP) to its V2 receptor (V2R) in the basolateral
      membrane of principal cells induces Aquaporin-2-mediated water reabsorption in
      the kidney. To study the regulation of the V2R by dDAVP in a proper model, a
      polarized renal cell line stably-expressing V2R-GFP was generated. Labeled AVP
      binding studies revealed an equal basolateral vs. apical membrane distribution
      for V2R-GFP and endogenous V2R. In these cells, GFP-V2R was expressed in its
      mature form and localized for 75% in the basolateral membrane and for 25% to late
      endosomes/lysosomes. dDAVP caused a dose- and time-dependent internalization of
      V2R-GFP, which was completed within 1 h with 100 nM dDAVP, was prevented by
      coincubation with a V2R antagonist, and which reduced its half-life from 11.5 to
      2.8 h. Semiquantification of the V2R-GFP colocalization with E-cadherin
      (basolateral membrane), early endosomal antigen-1 (EEA-1) and lysosome-associated
      membrane protein-2 (LAMP-2) in time revealed that most dDAVP-bound V2R was
      internalized via early endosomes to late endosomes/lysosomes, where it was
      degraded. The dDAVP-internalized V2R did not recycle to the basolateral membrane.
      In conclusion, we established the itinerary of the V2R in a polarized cell model
      that likely resembles the in vivo V2R localization and regulation by AVP to a
      great extent.

PMID- 15469989
TI  - p116Rip targets myosin phosphatase to the actin cytoskeleton and is essential for
      RhoA/ROCK-regulated neuritogenesis.
AB  - Activation of the RhoA-Rho kinase (ROCK) pathway stimulates actomyosin-driven
      contractility in many cell systems, largely through ROCK-mediated inhibition of
      myosin II light chain phosphatase. In neuronal cells, the RhoA-ROCK-actomyosin
      pathway signals cell rounding, growth cone collapse, and neurite retraction;
      conversely, inhibition of RhoA/ROCK promotes cell spreading and neurite
      outgrowth. The actin-binding protein p116(Rip), whose N-terminal region bundles F
      actin in vitro, has been implicated in Rho-dependent neurite remodeling; however,
      its function is largely unknown. Here, we show that p116(Rip), through its C
      terminal coiled-coil domain, interacts directly with the C-terminal leucine
      zipper of the regulatory myosin-binding subunits of myosin II phosphatase, MBS85
      and MBS130. RNA interference-induced knockdown of p116(Rip) inhibits cell
      spreading and neurite outgrowth in response to extracellular cues, without
      interfering with the regulation of myosin light chain phosphorylation. We
      conclude that p116(Rip) is essential for neurite outgrowth and may act as a
      scaffold to target the myosin phosphatase complex to the actin cytoskeleton.

PMID- 15469990
TI  - Insulin and hypertonicity recruit GLUT4 to the plasma membrane of muscle cells by
      using N-ethylmaleimide-sensitive factor-dependent SNARE mechanisms but different
      v-SNAREs: role of TI-VAMP.
AB  - Insulin and hypertonicity each increase the content of GLUT4 glucose transporters
      at the surface of muscle cells. Insulin enhances GLUT4 exocytosis without
      diminishing its endocytosis. The insulin but not the hypertonicity response is
      reduced by tetanus neurotoxin, which cleaves vesicle-associated membrane protein
      (VAMP)2 and VAMP3, and is rescued upon introducing tetanus neurotoxin-resistant
      VAMP2. Here, we show that hypertonicity enhances GLUT4 recycling, compounding its
      previously shown ability to reduce GLUT4 endocytosis. To examine whether the
      canonical soluble N-ethylmaleimide-sensitive factor attachment protein receptor
      (SNARE) mechanism is required for the plasma membrane fusion of the tetanus
      neurotoxin-insensitive GLUT4 vesicles, L6 myoblasts stably expressing myc-tagged
      GLUT4 (GLUT4myc) were transiently transfected with dominant negative N
      ethylmaleimide-sensitive factor (NSF) (DN-NSF) or small-interfering RNA to
      tetanus neurotoxin-insensitive VAMP (TI-VAMP siRNA). Both strategies markedly
      reduced the basal level of surface GLUT4myc and the surface gain of GLUT4myc in
      response to hypertonicity. The insulin effect was abolished by DN-NSF, but only
      partly reduced by TI-VAMP siRNA. We propose that insulin and hypertonicity
      recruit GLUT4myc from partly overlapping, but distinct sources defined by VAMP2
      and TI-VAMP, respectively.

PMID- 15469991
TI  - The Na+/H+ exchanger regulatory factor stabilizes epidermal growth factor
      receptors at the cell surface.
AB  - Ligand binding to cell surface receptors initiates both signal transduction and
      endocytosis. Although signaling may continue within the endocytic compartment,
      down-regulation is the major mechanism that controls the concentration of cell
      surface receptors, their ability to receive environmental signals, and the
      ultimate strength of biological signaling. Internalization, recycling, and
      trafficking of receptor tyrosine kinases (RTKs) within the endosome compartment
      are each regulated to control the overall process of down-regulation. We have
      identified the Na(+)/H(+) exchanger regulatory factor (NHERF) as an important
      molecular component that stabilizes epidermal growth factor receptors (EGFRs) at
      the cell surface to restrict receptor down-regulation. The NH(2)-terminal PDZ
      domain (PDZ 1) of NHERF specifically binds to an internal peptide motif located
      within the COOH-terminal regulatory domain of EGFR. Expression of NHERF slows the
      rate of EGF-induced receptor degradation. A point mutation that abolishes the PDZ
      1 recognition sequence of EGFR enhances the rate of ligand-induced endocytosis
      and down-regulation of EGFR. Similarly, expression of a dominant negative mutant
      of NHERF enhances EGF-induced receptor down-regulation. In contrast to beta
      adrenergic receptors where NHERF enhances recycling of internalized receptors,
      NHERF stabilizes EGFR at the cell surface and slows the rate of endocytosis
      without affecting recycling. Although the mechanisms differ, for both RTKs and G
      protein-coupled receptors, the overall effect of NHERF is to enhance the fraction
      of receptors present at the cell surface.

PMID- 15469992
TI  - Association of ABCA1 with syntaxin 13 and flotillin-1 and enhanced phagocytosis
      in tangier cells.
AB  - The ATP-binding cassette transporter A1 (ABCA1) facilitates the cellular release
      of cholesterol and choline-phospholipids to apolipoprotein A-I (apoA-I) and
      several studies indicate that vesicular transport is associated with ABCA1
      function. Syntaxins play a major role in vesicular fusion and have also been
      demonstrated to interact with members of the ABC-transporter family. Therefore,
      we focused on the identification of syntaxins that directly interact with ABCA1.
      The expression of syntaxins and ABCA1 in cultured human monocytes during M-CSF
      differentiation and cholesterol loading was investigated and syntaxins 3, 6, and
      13 were found induced in foam cells together with ABCA1. Immunoprecipitation
      experiments revealed a direct association of syntaxin 13 and full-length ABCA1,
      whereas syntaxin 3 and 6 failed to interact with ABCA1. The colocalization of
      ABCA1 and syntaxin 13 was also shown by immunofluorescence microscopy. Silencing
      of syntaxin 13 by small interfering RNA (siRNA) led to reduced ABCA1 protein
      levels and hence to a significant decrease in apoA-I-dependent choline
      phospholipid efflux. ABCA1 is localized in Lubrol WX-insoluble raft microdomains
      in macrophages and syntaxin 13 and flotillin-1 were also detected in these
      detergent resistant microdomains along with ABCA1. Syntaxin 13, flotillin-1, and
      ABCA1 were identified as phagosomal proteins, indicating the involvement of the
      phagosomal compartment in ABCA1-mediated lipid efflux. In addition, the uptake of
      latex phagobeads by fibroblasts with mutated ABCA1 was enhanced when compared
      with control cells and the recombinant expression of functional ABCA1 normalized
      the phagocytosis rate in Tangier fibroblasts. It is concluded that ABCA1 forms a
      complex with syntaxin 13 and flotillin-1, residing at the plasma membrane and in
      phagosomes that are partially located in raft microdomains.

PMID- 15469993
TI  - Deletions of single extracellular loops affect pH sensitivity, but not voltage
      dependence, of the Escherichia coli porin OmpF.
AB  - The molecular basis for the voltage and pH dependence of the Escherichia coli
      OmpF porin activity remains unknown. The L3 loop was previously shown not be
      involved in voltage dependence. Here we used seven OmpF mutants where single
      extracellular loops, except L3, were deleted one at a time. The proteins are
      expressed at levels comparable to wild-type and purified as trimers. Wild-type
      and mutant proteins were inserted into planar lipid bilayers for
      electrophysiological measurement of their activity. Current-voltage relationships
      show the typical porin channel closure at voltages greater than the critical
      voltage. Measurements of critical voltages for the seven deletion mutants showed
      no significant differences relative to wild-type, hence eliminating the role of
      single loops in voltage sensitivity. However, deletions of loops L1, L7 or L8
      affected the tendency of channels to close at acidic pH. Wild-type channels close
      more readily at acidic pH and their open probability is decreased by
      approximately 60% at pH 4.0 relative to pH 7.0. For mutants lacking loop L1, L7
      or L8, the channel open probability was found not to be significantly different
      at pH 4.0 than at pH 7.0. The other deletion mutants retained a pH sensitivity
      similar to the wild-type channel. Possible mechanistic scenarios for the voltage-
      and pH dependence of E.coli OmpF porin are discussed based on these results.

PMID- 15469994
TI  - Design of fully active FGF-1 variants with increased stability.
AB  - Fibroblast growth factor 1 is a powerful mitogen playing an important role in
      morphogenesis, angiogenesis and wound healing and is therefore of potential
      medical interest. Using homologous sequence and structure comparisons, we
      designed and constructed 16 mutants of FGF-1 with increased thermodynamic
      stability, as determined by chemical and heat denaturation. For multiple mutants,
      additive effects on stability were observed, providing mutants up to 7.8 degrees
      C more stable than the wild-type. None of the introduced mutations affected any
      FGF-1 biological activities, such as stimulation of DNA synthesis, MAP kinase
      activation and binding to the FGF receptor on the cell surface. Our study
      provides a good starting point to improve the stability of FGF-1 in the context
      of its wide potential therapeutic applications. We showed that a homology
      approach is an effective method to change the thermodynamic properties of the
      protein without altering its function.

PMID- 15469995
TI  - Affinity-dependent alterations of mouse B cell development by noninherited
      maternal antigen.
AB  - We have examined the passage of maternal cells into the fetus during the
      gestation and postpartum in mice. Using enhanced green fluorescent protein (EGFP)
      transgenic females, we showed that maternal cells frequently gain access to the
      fetus, mostly in syngeneic pregnancies, but also in allogeneic and outbred
      crosses. EGFP-transgenic cells, including B, T, and natural killer cells, can
      persist until adulthood, primarily in bone marrow and thymus. We then asked
      whether maternal cells, bearing antigens not inherited by the fetus, influence
      the development of fetal and neonatal B lymphocytes. We have used the B cell
      receptor 3-83 mu/delta transgenic mouse model, whose B cells recognize the major
      histocompatibility complex class I molecules H-2Kk and H-2Kb, with a high or
      moderate affinity, respectively. The fate of transgenic B cells in animals
      exposed to noninherited H-2Kk or H-2Kb maternal antigens (NIMA) during gestation
      and lactation was compared with those of nonexposed controls. In H-2Kk-exposed
      fetuses, NIMA-specific transgenic B cells are partially deleted during late
      gestation. Nondeleted cells have downmodulated their B cell receptor. In
      contrast, in NIMA H-2Kb-exposed neonates, transgenic B cells present an activated
      phenotype, including proliferation, upregulation of surface CD69, and
      preferential localization in the T cell zone of splenic follicles. This state of
      activation is still clearly detectable up to 3 wk of age. Thus, we show that
      fetal and neonatal B cell development is affected by maternal cells bearing
      antigens noninherited by the fetus and that this phenomenon is highly dependent
      on the affinity of the B cell receptor for the NIMA.

PMID- 15469996
TI  - Sry associates with the heterochromatin protein 1 complex by interacting with a
      KRAB domain protein.
AB  - In mammals, the SRY/Sry gene on the Y chromosome is necessary and sufficient for
      a bipotential gonad to develop into a testis, regardless of its chromosomal sex.
      The SRY/Sry gene encodes a protein that belongs to a high-mobility-group (HMG)
      box protein family and that has been postulated to modulate the expression of
      genes necessary for male gonadal differentiation. Using a yeast two-hybrid
      screen, we identified a novel protein containing only a Kruppel-associated box
      (KRAB) domain, which is hereafter named KRAB-O (KRAB Only), as an SRY-interacting
      protein. The KRAB-O protein is encoded by an alternatively spliced transcript
      from the Zfp208 locus that also produces another transcript coding for a KRAB
      zinc finger protein, ZFP208. The interaction of the mouse SRY with KRAB-O was
      further confirmed by glutathione S-transferase pull-down assay and
      coimmunoprecipitation in transfected COS7 cells. The KRAB-O interaction domain in
      both the human and mouse SRY was mapped to the bridge region outside the HMG box.
      Indirect immunofluorescence and confocal microscopy show that the mouse SRY
      colocalizes with KRAB-O in nuclear dots in transiently transfected COS7 cells and
      primary fetal mouse gonadal cells. Using similar approaches, we demonstrate that
      KRAB-O interacts directly with KAP1 (KRAB-associated protein 1), the obligatory
      corepressor for KRAB domain proteins. Furthermore, we show that the mouse SRY is
      associated indirectly with KAP1 and heterochromatin protein 1 (HP1) through its
      interaction with KRAB-O, suggesting that the mouse SRY could use the KRAB-KAP1
      HP1 organized transcriptional regulatory complex to regulate its yet-to-be
      identified downstream target genes.

PMID- 15469997
TI  - Progesterone upregulates calcitonin gene-related peptide and adrenomedullin
      receptor components and cyclic adenosine 3'5'-monophosphate generation in Eker
      rat uterine smooth muscle cell line.
AB  - Calcitonin gene-related peptide (CGRP) and adrenomedullin (AM), two potent smooth
      muscle relaxants, have been shown to cause uterine relaxation. Both CGRP- and AM
      binding sites in the uterus increase during pregnancy and decrease at labor and
      postpartum. These changes in binding sites appear to be related to the changes in
      calcitonin receptor-like receptor (CRLR), receptor activity-modified protein 1
      (RAMP1), RAMP2, and RAMP3 mRNA levels. It is not clear, however, whether the
      changes in the receptor components occur in the myometrial cells and whether the
      steroid hormones can directly alter these receptor components in the muscle
      cells. In addition, the mechanism of CGRP and AM signaling in the rat myometrium
      is not well understood. Therefore, we examined the mRNA expression of CGRP- and
      AM-receptor components, G protein Galphas, CGRP, and AM stimulation of cAMP and
      cGMP, and the effects of progesterone on these parameters in the Eker rat uterine
      myometrial smooth-muscle cell line (ELT3). ELT3 cells expressed CGRP- and AM
      receptor components CRLR, RAMP1, RAMP2, and RAMP3. Expression of CRLR and RAMP1
      mRNA increased with progesterone treatment and decreased with estradiol-17beta
      treatment. However, RAMP2 and RAMP3 mRNA expressions were unaltered by both
      progesterone and estradiol. Progesterone increased (P<0.05) Galphas expression
      and augmented CGRP- and AM-induced increases in cAMP levels. In uterine smooth
      muscle cells, the antagonist to Galphas protein NF449 decreased basal as well as
      CGRP- and AM-stimulated cAMP levels. None of the cell treatments affected cyclic
      GMP production. Our results suggest that the progesterone-stimulated increases in
      CGRP and AM receptors, Galphas protein levels, and cAMP generation in the
      myometrial cells may be responsible for increased uterine relaxation sensitivity
      to CGRP and AM during pregnancy.

PMID- 15469998
TI  - Cytoplasmic impact on cross-genus cloned fish derived from transgenic common carp
      (Cyprinus carpio) nuclei and goldfish (Carassius auratus) enucleated eggs.
AB  - In previous studies of nuclear transplantation, most cloned animals were obtained
      by intraspecies nuclear transfer and are phenotypically identical to their
      nuclear donors; furthermore, there was no further report on successful fish
      cloning since the report of cloned zebrafish. Here we report the production of
      seven cross-genus cloned fish by transferring nuclei from transgenic common carp
      into enucleated eggs of goldfish. Nuclear genomes of the cloned fish were
      exclusively derived from the nuclear donor species, common carp, whereas the
      mitochondrial DNA from the donor carp gradually disappeared during the
      development of nuclear transfer (NT) embryos. The somite development process and
      somite number of nuclear transplants were consistent with the recipient species,
      goldfish, rather than the nuclear donor species, common carp. This resulted in a
      long-lasting effect on the vertebral numbers of the cloned fish, which belonged
      to the range of goldfish. These demonstrate that fish egg cytoplasm not only can
      support the development driven by transplanted nuclei from a distantly related
      species at the genus scale but also can modulate development of the nuclear
      transplants.

PMID- 15469999
TI  - Reduced expression of MAD2, BCL2, and MAP kinase activity in pig oocytes after in
      vitro aging are associated with defects in sister chromatid segregation during
      meiosis II and embryo fragmentation after activation.
AB  - This study was conducted to examine expression of centromere protein B (CENPB),
      spindle checkpoint protein MAD2 (mitotic arrest deficient protein), and
      antiapoptotic protein BCL2; activities of MAPK (mitogen-activated protein kinase)
      and mitochondria distribution in pig oocytes during aging, and their relationship
      with sister chromatid separation during meiosis II and embryo fragmentation and
      apoptosis after activation. After immature oocytes were cultured for 40-72 h,
      CENPB, MAD2, tubulin, BCL2, and MAPK in the oocytes were examined by
      immunoblotting. Spindles, chromosomes, kinetochores, and mitochondria were
      examined by immunofluorescence staining and apoptosis was examined by TUNEL
      assay. It was found that tubulin and CENPB was not changed during 40-72 h of
      culture. However, the expression of MAD2 and BCL2 and the activity of MAPK were
      gradually reduced during oocyte aging. The percentages of oocytes with normal
      spindle, chromosomes, and kinetochores were also reduced as oocyte aged from 9.5%
      at 40 h to 17.3%, 34.6%, and 42.9% at 48, 60, and 72 h, respectively. Aggregated
      mitochondria were found in the aged oocytes as compared with the uniform
      distribution in young oocytes. After activation, the proportions of oocytes with
      abnormal anaphase II were significantly increased in aged oocytes. More (P<0.001)
      oocytes cultured for 60-72 h fragmented and showed apoptosis after activation as
      compared with the oocytes cultured for 40-48 h. This study indicates that aging
      reduces expression in spindle checkpoint protein and antiapoptosis protein and
      MAPK activity in pig oocytes. These events in turn cause abnormal sister
      chromatid segregation during meiosis II, embryo fragmentation, and apoptosis.

PMID- 15470000
TI  - Establishment of spermatogenesis in neonatal bovine testicular tissue following
      ectopic xenografting varies with donor age.
AB  - Ectopic testicular xenografting can be used to investigate spermatogenesis and as
      an alternative means for generating transgenic spermatozoa in many species.
      Improving the efficiency of spermatogenesis in xenografted testicular tissue will
      aid in the application of using this approach. The present study was conducted to
      evaluate age-related differences in the establishment of spermatogenesis in
      grafted testicular tissue from bulls between 2 and 16 wk of life. Testicular
      tissue was ectopically xenografted under the skin on the backs of castrated nude
      mice and subsequently evaluated for growth, testosterone production, and
      establishment of spermatogenesis 24 wk after grafting. The greatest weight
      increases occurred in donor tissue from calves of the ages 2, 4, and 8 wk
      compared with the ages of 12 and 16 wk. Recipient mouse serum testosterone
      concentration was at normal physiological levels 24 wk after grafting and no
      significant differences were detected between recipients grafted with testicular
      tissue from bull calves of different ages. The development of germ cells to
      elongated spermatids were observed in seminiferous tubules of grafts from donor
      calves of the ages 4, 8, 12, and 16 wk but not observed in grafts from 2-wk
      donors, which contained round spermatids as the most advanced germ cell stage.
      Grafts from 8-wk donors contained a significantly higher (10-fold) average
      percentage of seminiferous tubules with elongated spermatids than all other donor
      ages. These data demonstrate differences in the ability of testicular tissue from
      donor animals of different ages to establish spermatogenesis following ectopic
      testicular xenografting.

PMID- 15470001
TI  - MTNR1A melatonin receptors in the ovine premammillary hypothalamus: day-night
      variation in the expression of the transcripts.
AB  - Melatonin regulation of reproductive functions in sheep is mediated by action in
      the premammillary hypothalamus (PMH). The aim of this study was to identify the
      high-affinity melatonin-receptor subtypes expressed in this structure. To achieve
      this, we used reverse transcription-polymerase chain reaction (RT-PCR) and
      developed in situ hybridization techniques (ISH). By using RT-PCR, we detected a
      band corresponding to the MTNR1A melatonin-receptor cDNA in the PMH as well as in
      the pars tuberalis (PT). On the opposite, MTNR1B melatonin-receptor transcripts
      were not detected using degenerate primers in any of the structures considered,
      confirming the lack of expression of this receptor subtype in sheep. The
      expression of MTNR1A mRNA was further confirmed in the PMH by ISH with a 35S
      labeled ovine MTNR1A riboprobe. We next investigated the variation in the
      expression of MTNR1A mRNA between the end of the day and the end of the night
      (absence and presence of melatonin, respectively). MTNR1A transcript expression
      was greater at the end of the night than at the end of the day in the PMH. In
      contrast, MTNR1A mRNA expression was lower at the end of the night than at the
      end of the day in the PT. No significant variation in the MTNR1A mRNA expression
      was observed in a more dorsal hypothalamic area. Overall, these results show that
      MTNR1A transcripts are expressed in the ovine PMH and that their expression
      follows a diurnal rhythm, which is different from the pattern of expression
      observed in the PT.

PMID- 15470002
TI  - Effects of neonatal exposure to diethylstilbestrol, tamoxifen, and toremifene on
      the BALB/c mouse mammary gland.
AB  - In this study, we compared the long-term effects of neonatal exposure to
      diethylstilbestrol (DES, 0.0125-50 microg), tamoxifen (TAM, 0.0125-50 microg),
      and toremifene (TOR, 53 microg) on mammary gland development and differentiation.
      Allometric growth of the mammary ducts was stimulated by neonatal DES exposure
      (12.5 microg) and impaired by exposure to TAM (25 microg). Neonatal treatment
      with high doses of DES resulted in mammary ducts that displayed extensive
      dilatation and precocious lactogenesis in postpubertal, nulliparous females.
      Initiation of this precocious differentiation coincided with the absence of
      corpora lutea, increased levels of serum prolactin (PRL), and the induction of
      Prl mRNA expression within the mammary glands. Neonatal exposure to 1.25 microg
      TAM increased alveolar development in postpubertal, nulliparous females similar
      to that recorded in females treated with low doses of DES. Lower doses of TAM did
      not affect alveolar development, whereas branching morphogenesis and alveolar
      development were impaired by higher doses. Increased alveolar development in
      females exposed to 1.25 microg TAM was associated with elevated serum
      progesterone (P) and increased alveolar development in response to exogenous P.
      Taken together, our findings demonstrate that neonatal exposure to both DES and
      TAM exerts long-lasting effects on the proliferation and differentiation of the
      mammary glands in female BALB/c, primarily as the result of endocrine disruption.

PMID- 15470003
TI  - Reducing injury from speed related road crashes.

PMID- 15470004
TI  - International Collaborative Effort on Injury Statistics: 10 year review.
AB  - International comparisons of injury data may be useful for examining differences
      in risk and for suggesting potential interventions or hypotheses for future
      studies. However important issues to be considered in conducting comparisons are
      related to both the underlying quality of the data and how the data are
      collected. The International Collaborative Effort (ICE) on Injury Statistics grew
      out of concerns over the comparability of international injury data. This article
      outlines the history behind the development of the Injury ICE, brief descriptions
      of current and past projects, collaborations, and reflections on the value of
      collaboration.

PMID- 15470005
TI  - What makes community based injury prevention work? In search of evidence of
      effectiveness.
AB  - Community based injury prevention work has become a widely accepted strategy
      among safety promotion specialists. Hundreds of community based injury prevention
      programs have been implemented since the mid-1970s, but relatively few have been
      evaluated rigorously, resulting in a lack of consensus regarding the
      effectiveness of this approach. This study sought to identify key components that
      contribute to the effectiveness of these programs. The objective was to gain a
      better understanding of the community based model for injury prevention. The
      study was performed as a structured review of existing evaluations of injury
      prevention programs that employed multiple strategies to target different age
      groups, environments, and situations. The results of this study suggested that
      there are complex relationships between the outcome and the context, structure,
      and process of community-wide injury prevention programs. The interconnectedness
      of these variables made it difficult to provide solid evidence to prioritise in
      terms of program effectiveness. The evaluations of multifaceted community
      oriented injury prevention programs were found to have many shortcomings. Meagre
      descriptions of community characteristics and conditions, insufficient assessment
      of structural program components, and failure to establish process-outcome
      relationships contributed to the difficulty of identifying key success factors of
      the programs.

PMID- 15470006
TI  - Quality of information on risk factors reported by ski patrols.
AB  - OBJECTIVE: To determine the reliability of reporting of information on risk
      factors from a standard accident report form used by ski patrols and a follow up
      mail questionnaire or telephone interview among injured skiers and snowboarders.
      SETTING: 19 ski areas in the Canadian province of Quebec between November 2001
      and April 2002. PARTICIPANTS: 4377 injured skiers and snowboarders seen by the
      ski patrol, who completed a follow up mail questionnaire or telephone interview.
      MAIN OUTCOME MEASURES: Kappa and weighted kappa statistics were used to measure
      the chance corrected agreement for self reported ability, age, skiing time on day
      of injury, lessons, type of practice, use of helmet at time of injury, and hill
      difficulty. RESULTS: The kappa value for helmet use at the time of injury was
      0.88 (95% confidence interval 0.87 to 0.90) and for other risk factors ranged
      from 0.45 (skiing time on day of injury) to 0.98 (age). Few differences were seen
      in reporting by body region of injury. Reporting consistency was lower for
      respondents who completed telephone interviews compared with those who completed
      mail questionnaires and those who responded more than four months after the
      injury. CONCLUSIONS: Moderate to almost perfect agreement, depending on the risk
      factor, exists between ski patrols' accident report forms and follow up
      information. Ski patrol reports can be a reliable and readily available source of
      information on risk factors for skiing and snowboarding.

PMID- 15470007
TI  - Firearm related deaths: the impact of regulatory reform.
AB  - OBJECTIVES: To examine trends in rates of firearm related deaths in Victoria,
      Australia, over 22 years in the context of legislative reform and describe and
      investigate impact measures to explain trends. DESIGN: Mortality data were
      extracted from vital statistics for 1979-2000. Data on firearm related deaths
      that were unintentional deaths, assaults, suicides, and of undetermined intent
      were analyzed. Rates were calculated with population data derived from estimates
      by the Australian Bureau of Statistics. A quasi-experimental design that used a
      Poisson regression model was adopted to compare relative rates of firearm related
      deaths for Victoria and the rest of Australia over three critical periods of
      legislative reform. The Wilcoxon signed ranks test was used to assess changes in
      the types of firearm related deaths before and after 1998. RESULTS: In Victoria,
      two periods of legislative reform related to firearms followed mass shooting
      events in 1988 and 1996. A national firearm amnesty and buyback scheme followed
      the latter. Victorian and Australian rates of firearm related deaths before
      reforms (1979-86) were steady. After initial Victorian reforms, a significant
      downward trend was seen for numbers of all firearm related deaths between 1988
      and 1995 (17.3% in Victoria compared with the rest of Australia, p<0.0001). A
      further significant decline between 1997 and 2000 followed the later reforms.
      After the later all state legislation, similar strong declines occurred in the
      rest of Australia from 1997 (14.0% reduction compared with Victoria, p = 0.0372).
      Victorian reductions were observed in frequencies of firearm related suicides,
      assaults, and unintentional deaths before and after the 1988 reforms, but
      statistical significance was reached only for suicide. CONCLUSION: Dramatic
      reductions in overall firearm related deaths and particularly suicides by
      firearms were achieved in the context of the implementation of strong regulatory
      reform.

PMID- 15470008
TI  - Urban youths' perspectives on violence and the necessity of fighting.
AB  - OBJECTIVES: To assess youth perceptions of the causes and consequences of
      violence generally, the causes and consequences of fighting specifically, and to
      determine how best to approach fighting in the context of violence prevention
      activities. METHODS: Thirteen structured focus group interviews with youths from
      three high violence urban settings: a large, urban high school, a training center
      for disadvantaged youths, and a school for adjudicated youths. Participants were
      120 urban, predominately African-American youths and young adults ages 14-22
      years (mean: 17.2 years). Seven focus groups were conducted with females, and six
      with males. RESULTS: Adolescents identified the causes of violence on multiple
      levels including: individual, family, interpersonal, and community level factors.
      Most youths (89%) had been in a physical fight. Participants felt that fighting
      was not "right", but identified situations in which it was necessary.
      Specifically, fighting was used as a problem solving tool, and could prevent
      escalation of violence. Youths felt that the adults in their lives, including
      physicians, were generally ill equipped to give advice about violence, as adults'
      experiences were so removed from their own. Participants looked to experienced
      role models to offer problem solving and harm reduction strategies. Youths were
      open to receiving anticipatory guidance about violence and fighting from primary
      care physicians they felt comfortable with, and who showed respect for their
      experiences. CONCLUSIONS: Interventions that include blanket admonitions against
      fighting should be reassessed in light of youth perceptions that fighting plays a
      complex role in both inciting and preventing more serious violence.

PMID- 15470009
TI  - Cochrane Injuries Group.

PMID- 15470010
TI  - How low can they go? Potential for reduction in work injury rates.
AB  - BACKGROUND: There is a considerable variability in occupational injury rates
      across companies, even within the same industry. The aim of this study was to
      estimate how many injuries could be prevented if all firms could achieve the
      performance of their better peers. METHOD: Data were obtained from the Workplace
      Safety & Insurance Board of Ontario on all insured firms in the province. Within
      rate groups (firms in the same type of business) the number of injuries expected
      if all firms had a lost time injury rate at the 25th percentile of the
      distribution for the rate group were estimated. The total number of injuries were
      compared with the expected number, after adjusting for firm size and type of
      injury. RESULTS: Overall, using the 25th percentile as a benchmark, 42% of lost
      time injuries in Ontario could be prevented. DISCUSSION: There is considerable
      potential for prevention of work injuries based on currently achieved, non
      optimal benchmarks.

PMID- 15470011
TI  - Risk factors for work related violence in a health care organization.
AB  - OBJECTIVE: Identify the exposure effects of job family, patient contact, and
      supervisor support on physical and non-physical work related violence. DESIGN:
      Cross sectional study of employees in a Midwest health care organization,
      utilizing a specially designed mailed questionnaire and employer secondary data.
      SUBJECTS: Respondents included 1751 current and former employees (42% response
      rate). RESULTS: Physical and non-physical violence was experienced by 127 (7.2%)
      and 536 (30.6%) of the respondents, respectively. Multivariate analyses of
      physical violence identified increased odds for patient care assistants (odds
      ratio (OR) 2.5, 95% confidence interval (CI) 1. 1 to 6.1) and decreased odds for
      clerical workers (OR 0.1, 95% CI 0.03 to 0.5). Adjusted for job family, increased
      odds of physical violence were identified for moderate (OR 5.9, 95% CI 2.1 to
      16.0) and high (OR 7.8, 95% CI 2.9 to 20.8) patient contact. Similar trends were
      identified for non-physical violence (OR 1.4, 95% CI 1.1 to 2.0 and OR 1.7, 95%
      CI 1.3 to 2.3). Increased supervisor support decreased the odds of both physical
      (OR 0.7, 95% CI 0.6 to 0.95) and non-physical violence (OR 0.5, 95% CI 0.4 to
      0.6), adjusting for job family and demographic characteristics. CONCLUSIONS:
      Increased odds of physical violence were identified for the job family of nurses,
      even when adjusted for patient contact. Increased patient contact resulted in
      increased physical and non-physical violence, independent of job family, while
      supervisor support resulted in decreased odds of physical and non-physical
      violence.

PMID- 15470012
TI  - All-terrain vehicle injury in children: strategies for prevention.
AB  - OBJECTIVE: A variety of educational efforts, policies, and regulations have been
      adopted to reduce all-terrain vehicle (ATV) injury in children. Despite this, ATV
      use by children continues and serious injuries are common. The purpose of this
      study was to investigate the knowledge, practices, and beliefs of ATV users to
      help develop effective educational strategies to promote safer ATV use. DESIGN:
      Focus groups were conducted to characterize participant ATV use and safety
      awareness as well as to explore avenues for prevention. Feedback on draft ATV
      safety public service announcements was elicited. Themes of transcribed focus
      group data were summarized. SETTING: Rural state with high ATV use and injury
      rates. SUBJECTS: Adult and adolescent ATV users. INTERVENTIONS: None. MAIN
      OUTCOME MEASURES: Summaries of focus group discussions. RESULTS: ATV riders
      frankly discussed current use and safety behaviors and were aware of some ATV
      risks. Youths felt that age specific regulation was unlikely to be a helpful
      strategy. Participants endorsed messages demonstrating graphic consequences as
      likely to get the attention of young riders regarding risks. Educational settings
      were suggested, including hunter and driver safety classes. CONCLUSIONS: Efforts
      to improve ATV safety awareness should clearly show pediatric ATV injury risk and
      safety practices. Campaigns must also show realistic understanding of current use
      practices to be credible for users. Messages emphasizing the consequences of ATV
      use were endorsed as most likely to have impact. Approaches based on age based
      restrictions were considered unrealistic and alternative strategies were
      suggested.

PMID- 15470014
TI  - Lost working days, productivity, and restraint use among occupants of motor
      vehicles that crashed in the United States.
AB  - BACKGROUND: In 2001, 6.3 million passengers were involved in motor vehicle
      crashes. This study aimed to determine the number of work days lost as a result
      of motor vehicle crashes and factors that influenced people's return to work.
      METHODS: This was a retrospective, population based cohort study of occupants in
      motor vehicles involved in crashes from the 1993-2001 Crashworthiness Data System
      produced by the National Highway Traffic Safety Administration. The sample
      population of people aged 18-65 years included two groups: occupants who survived
      and were working before the crash and occupants who were injured fatally and were
      estimated to have been working before the crash. Multivariate linear regression
      was used to analyze the impact of restraint use and injury type on return to
      work. RESULTS: Overall, 30.1% of occupants of vehicles that crashed missed one or
      more days of work. A crash resulted in a mean 28.0 (95% confidence interval 15.8
      to 40.1) days lost from work, including losses associated with fatalities. The
      2.1 million working occupants of vehicles that crashed in 2001 lost a total of 60
      million days of work, resulting in annual productivity losses of over $7.5
      billion (2964 to 12 075). Unrestrained vehicle occupants accounted for $5.6
      billion in lost productivity. CONCLUSIONS: Motor vehicle crashes result in large
      and potentially preventable productive losses that are mostly attributable to
      fatal injuries.

PMID- 15470013
TI  - Risk factors for serious fall related injury in elderly women living at home.
AB  - OBJECTIVES: To study whether balance, function, and other health status
      indicators can predict serious fall related injury in elderly women living at
      home. METHODS: In this prospective study, the authors took a random sample of 307
      women aged 75 years and over (mean 80.8 years, response rate 74.5%), living in
      the community. Serious fall injuries which occurred over a period of during one
      year were recorded, together with baseline registrations of health, function, and
      tests of walking and balance. RESULTS: In all, 155 women (50.5%) fell one or more
      times. One hundred and fifty six (51%) of the 308 falls resulted in a fall
      related injury, 74 (24%) in a serious fall related injury, and 40 falls (13%)
      resulted in fractures. The presence of rheumatic disorders, inability to rise
      from the floor, arthrosis of the hip, having had more than one fall during the
      one year follow up period, and an increased tendency to sway in the frontal plane
      when doing a calculation task were independent and significant predictors for
      serious fall related injury (fractures included). The independent predictors of
      fall induced fractures were experiencing more than one fall in the follow up
      period, cognitive impairment, and receiving care from professional or other.
      CONCLUSION: The study suggests that rheumatic disorders and the inability to get
      up from lying on the floor were the strongest independent risk factors for
      serious fall related injury. Experiencing more than one fall in the follow up
      period and cognitive impairment are the strongest independent predictors for fall
      induced fractures. Age was not a significant predictor of serious fall related
      injury. Assessment of these markers is feasible in a clinical setting and is a
      useful way of identifying those who are at risk of serious fall related injuries.

PMID- 15470015
TI  - Secreted immunomodulatory viral proteins as novel biotherapeutics.
AB  - Many viruses have learned to evade or subvert the host antiviral immune responses
      by encoding and expressing immunomodulatory proteins that protect the virus from
      attack by elements of the innate and acquired immune systems. Some of these viral
      anti-immune regulators are expressed as secreted proteins that engage specific
      host immune targets in the extracellular environment, where they exhibit potent
      anti-immune properties. We review here viral immunomodulatory proteins that have
      been tested as anti-inflammatory reagents in animal models of disease caused by
      excessive inflammation or hyperactivated immune pathways. The potential for such
      viral molecules for the development of novel drugs to treat immune-based or
      inflammatory disorders is discussed.

PMID- 15470016
TI  - Cutting edge: productive HIV-1 infection of dendritic cells via complement
      receptor type 3 (CR3, CD11b/CD18).
AB  - In the present study, we demonstrate that macrophage-tropic HIV-1 opsonized by
      complement and limited amounts of anti-HIV-IgG causes up to 10-fold higher
      productive infection of human monocyte-derived dendritic cells than HIV treated
      with medium or HIV opsonized by Ab only. Enhanced infection is completely
      abolished by a mAb specific for the ligand-binding site of CD11b (i.e., alpha
      chain of complement receptor 3, receptor for iC3b), proving the importance of
      complement receptor 3 in this process. Inhibition of complement activation by
      EDTA also prevents enhanced infection, further demonstrating the role of
      complement in virus uptake and productive infection. Since HIV is, even in the
      absence of Abs, regularly opsonized by complement, most probably the above
      described mechanism plays a role during in vivo primary infection.

PMID- 15470017
TI  - Rebuilding an immune-mediated central nervous system disease: weighing the
      pathogenicity of antigen-specific versus bystander T cells.
AB  - Although both self- and pathogen-specific T cells can participate in tissue
      destruction, recent studies have proposed that after viral infection, bystander T
      cells of an irrelevant specificity can bypass peptide-MHC restriction and
      contribute to undesired immunopathological consequences. To evaluate the
      importance of this mechanism of immunopathogenesis, we determined the relative
      contributions of Ag-specific and bystander CD8+ T cells to the development of CNS
      disease. Using lymphocytic choriomeningitis virus (LCMV) as a stimulus for T cell
      recruitment into the CNS, we demonstrate that bystander CD8+ T cells with an
      activated surface phenotype can indeed be recruited into the CNS over a chronic
      time window. These cells become anatomically positioned in the CNS parenchyma,
      and a fraction aberrantly acquires the capacity to produce the effector cytokine,
      IFN-gamma. However, when directly compared with their virus-specific
      counterparts, the contribution of bystander T cells to CNS damage was
      insignificant in nature (even when specifically activated). Although bystander T
      cells alone failed to cause tissue injury, transferring as few as 1000 naive LCMV
      specific CD8+ T cells into a restricted repertoire containing only bystander T
      cells was sufficient to induce immune-mediated pathology and reconstitute a fatal
      CNS disease. These studies underscore the importance of specific T cells in the
      development of immunopathology and subsequent disease. Because of highly
      restrictive constraints imposed by the host, it is more likely that specific,
      rather than nonspecific, bystander T cells are the active participants in T cell
      mediated diseases that afflict humans.

PMID- 15470018
TI  - A novel model for lymphocytic infiltration of the thyroid gland generated by
      transgenic expression of the CC chemokine CCL21.
AB  - Lymphocytic infiltrates and lymphoid follicles with germinal centers are often
      detected in autoimmune thyroid disease (AITD), but the mechanisms underlying
      lymphocyte entry and organization in the thyroid remain unknown. We tested the
      hypothesis that CCL21, a chemokine that regulates homeostatic lymphocyte
      trafficking, and whose expression has been detected in AITD, is involved in the
      migration of lymphocytes to the thyroid. We show that transgenic mice expressing
      CCL21 from the thyroglobulin promoter (TGCCL21 mice) have significant lymphocytic
      infiltrates, which are topologically segregated into B and T cell areas. Although
      high endothelial venules expressing peripheral lymph node addressin were
      frequently observed in the thyroid tissue, lymphocyte recruitment was independent
      of L-selectin or lymphotoxin-alpha but required CCR7 expression. Taken together,
      these results indicate that CCL21 is sufficient to drive lymphocyte recruitment
      to the thyroid, suggest that CCL21 is involved in AITD pathogenesis, and
      establish TGCCL21 transgenic mice as a novel model to study the formation and
      function of lymphoid follicles in the thyroid.

PMID- 15470019
TI  - The role of dendritic cells in selection of classical and nonclassical CD8+ T
      cells in vivo.
AB  - T cell development is determined by positive and negative selection events. An
      intriguing question is how signals through the TCR can induce thymocyte survival
      and maturation in some and programmed cell death in other thymocytes. This
      paradox can be explained by the hypothesis that different thymic cell types
      expressing self-MHC/peptide ligands mediate either positive or negative selection
      events. Using transgenic mice that express MHC class I (MHC-I) selectively on DC,
      we demonstrate a compartmentalization of thymic functions and reveal that DC
      induce CTL tolerance to MHC-I-positive hemopoietic targets in vivo. However, in
      normal and bone marrow chimeric mice, MHC-I+ DC are sufficient to positively
      select neither MHC-Ib (H2-M3)- nor MHC-Ia (H2-K)-restricted CD8+ T cells. Thus,
      thymic DC are specialized in tolerance induction, but cannot positively select
      the vast majority of MHC-I-restricted CD8+ T cells.

PMID- 15470020
TI  - A-kinase anchoring proteins interact with phosphodiesterases in T lymphocyte cell
      lines.
AB  - The cAMP protein kinase A (PKA) pathway in T cells conveys an inhibitory signal
      to suppress inflammation. This study was performed to understand the mechanisms
      involved in cAMP-mediated signaling in T lymphocytes. A-kinase anchoring proteins
      (AKAPs) bind and target PKA to various subcellular locations. AKAPs also bind
      other signaling molecules such as cyclic nucleotide phosphodiesterases (PDEs)
      that hydrolyze cAMP in the cell. PDE4 and PDE7 have important roles in T cell
      activation. Based on this information, we hypothesized that AKAPs associate with
      PDEs in T lymphocytes. Immunoprecipitation of Jurkat cell lysates with Abs
      against both the regulatory subunit of PKA (RIIalpha) and specific AKAPs resulted
      in increased PDE activity associated with RIIalpha and AKAP95, AKAP149, and
      myeloid translocation gene (MTG) compared with control (IgG). Immunoprecipitation
      and pull-down analyses demonstrate that PDE4A binds to AKAP149, AKAP95, and MTG,
      but not AKAP79, whereas PDE7A was found to bind only MTG. Further analysis of
      MTG/PDE association illustrated that PDE4A and PDE7A bind residues 1-344 of
      MTG16b. Confocal analysis of HuT 78 cells stained with anti-PDE7A showed
      overlapping staining patterns with the Golgi marker GM130, suggesting that PDE7A
      is located in the Golgi. The staining pattern of PDE7A also showed similarity to
      the staining pattern of MTG, supporting the immunoprecipitation data and
      suggesting that MTG may interact with PDE7A in the Golgi. In summary, these data
      suggest that AKAPs interact with both PKA and PDE in T lymphocytes and thus are a
      key component of the signaling complex regulating T cell activation.

PMID- 15470021
TI  - Localization of marginal zone macrophages is regulated by C-C chemokine ligands
      21/19.
AB  - The marginal zone (MZ) of the spleen is an important site for the capture of
      blood-borne pathogens and a gateway for lymphocytes entering the white pulp. We
      have recently reported that Leishmania donovani infection results in a remarkably
      selective loss of MZ macrophages (MZM) from the MZ. To understand the basis of
      this observation, we have investigated how MZM maintain their anatomical
      distribution in the steady state in uninfected mice. We now report that plt/plt
      mice, which lack functional CCL19 and CCL21, have significantly reduced numbers
      of MZM compared with normal C57BL/6 (B6) mice. Similarly, in B6.CD45.1-->plt/plt
      chimeras, donor-derived MZM were rare compared with the number observed in
      reciprocal plt/plt-->B6.CD45.1 chimeras. Moreover, we show that administration of
      pertussis toxin, an inhibitor of chemokine receptor signaling, to B6 mice results
      in exit of MZM from the MZ, that MZM can migrate in response to CCL19 and CCL21
      in vitro, and that MZM colocalize with CD31+CCL21+ endothelial cells.
      Collectively, these data indicate that CCL21 and, to a lesser extent, CCL19 play
      significant roles in the distinctive localization of MZM within the splenic MZ.
      Deficiency of CCL19 and CCL21, as also previously observed in mice infected with
      L. donovani, may thus account for the selective loss of MZM seen during this
      infection.

PMID- 15470022
TI  - Th2 response of human peripheral monocytes involves isoform-specific induction of
      monoamine oxidase-A.
AB  - Monocyte/macrophage function is critically regulated by specific cytokines and
      growth factors that they are exposed to at inflammatory sites. IL-4 and IL-13 are
      multifunctional cytokines generated mainly by Th2 lymphocytes that have important
      biological activities in allergy and inflammation. The Th2 response of human
      peripheral monocytes is characterized by complex alterations in the gene
      expression pattern, which involves dominant expression of CD23 cell surface Ag
      and lipid-peroxidizing 15-lipoxygenase-1 (15-LOX1). In this study, we report that
      the classical Th2 cytokines IL-4 and IL-13 strongly up-regulate expression of
      monoamine oxidase A (MAO-A) with no induction of the closely related isozyme, MAO
      B. Real-time PCR indicated a >2000-fold up-regulation of the MAO-A transcripts,
      and immunohistochemistry revealed coexpression of the enzyme with 15-LOX1 in a
      major subpopulation of monocytes. MAO-A was also induced in lung carcinoma A549
      cells by IL-4 in parallel with 15-LOX1. In promyelomonocytic U937 cells, which
      neither express 15-LOX1 nor MAO-A in response to IL-4 stimulation, expression of
      MAO-A was up-regulated following transfection with 15-LOX1. This is the first
      report indicating expression of MAO-A in human monocytes. Its isoform-specific up
      regulation in response to Th2 cytokines suggests involvement of the enzyme in
      modulation of innate and/or acquired immune system.

PMID- 15470023
TI  - A novel pathway of alloantigen presentation by dendritic cells.
AB  - In the context of transplantation, dendritic cells (DCs) can sensitize
      alloreactive T cells via two pathways. The direct pathway is initiated by donor
      DCs presenting intact donor MHC molecules. The indirect pathway results from
      recipient DCs processing and presenting donor MHC as peptide. This simple
      dichotomy suggests that T cells with direct and indirect allospecificity cannot
      cross-regulate each other because distinct APCs are involved. In this study we
      describe a third, semidirect pathway of MHC alloantigen presentation by DCs that
      challenges this conclusion. Mouse DCs, when cocultured with allogeneic DCs or
      endothelial cells, acquired substantial levels of class I and class II
      MHC:peptide complexes in a temperature- and energy-dependent manner. Most
      importantly, DCs acquired allogeneic MHC in vivo upon migration to regional lymph
      nodes. The acquired MHC molecules were detected by Ab staining and induced
      proliferation of Ag-specific T cells in vitro. These data suggest that recipient
      DCs, due to acquisition of donor MHC molecules, may link T cells with direct and
      indirect allospecificity.

PMID- 15470024
TI  - Marrow stromal cells and osteoclast precursors differentially contribute to TNF
      alpha-induced osteoclastogenesis in vivo.
AB  - The marrow stromal cell is the principal source of the key osteoclastogenic
      cytokine receptor activator of NF-kappaB (RANK) ligand (RANKL). To individualize
      the role of marrow stromal cells in varying states of TNF-alpha-driven osteoclast
      formation in vivo, we generated chimeric mice in which wild-type (WT) marrow,
      immunodepleted of T cells and stromal cells, is transplanted into lethally
      irradiated mice deleted of both the p55 and p75 TNFR. As control, similarly
      treated WT marrow was transplanted into WT mice. Each group was administered
      increasing doses of TNF-alpha. Exposure to high-dose cytokine ex vivo induces
      exuberant osteoclastogenesis irrespective of in vivo TNF-alpha treatment or
      whether the recipient animals possess TNF-alpha-responsive stromal cells. In
      contrast, the osteoclastogenic capacity of marrow treated with lower-dose TNF
      alpha requires priming by TNFR-bearing stromal cells in vivo. Importantly, the
      osteoclastogenic contribution of cytokine responsive stromal cells in vivo
      diminishes as the dose of TNF-alpha increases. In keeping with this conclusion,
      mice with severe inflammatory arthritis develop profound osteoclastogenesis and
      bone erosion independent of stromal cell expression of TNFR. The direct induction
      of osteoclast recruitment by TNF-alpha is characterized by enhanced RANK
      expression and sensitization of precursor cells to RANKL. Thus, osteolysis
      attending relatively modest elevations in ambient TNF-alpha depends upon
      responsive stromal cells. Alternatively, in states of severe periarticular
      inflammation, TNF-alpha may fully exert its bone erosive effects by directly
      promoting the differentiation of osteoclast precursors independent of cytokine
      responsive stromal cells and T lymphocytes.

PMID- 15470025
TI  - TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts
      potentiates TCR signaling.
AB  - Ligation of the TCR along with the coreceptor CD28 is necessary to elicit T cell
      activation in vivo, whereas TCR triggering alone does not allow a full T cell
      response. Upon T cell activation of human peripheral blood T cells, we found that
      the majority of cAMP was generated in T cell lipid rafts followed by activation
      of protein kinase A. However, upon TCR and CD28 coligation, beta-arrestin in
      complex with cAMP-specific phosphodiesterase 4 (PDE4) was recruited to lipid
      rafts which down-regulated cAMP levels. Whereas inhibition of protein kinase A
      increased TCR-induced immune responses, inhibition of PDE4 blunted T cell
      cytokine production. Conversely, overexpression of either PDE4 or beta-arrestin
      augmented TCR/CD28-stimulated cytokine production. We show here for the first
      time that the T cell immune response is potentiated by TCR/CD28-mediated
      recruitment of PDE4 to lipid rafts, which counteracts the local, TCR-induced
      production of cAMP. The specific recruitment of PDE4 thus serves to abrogate the
      negative feedback by cAMP which is elicited in the absence of a coreceptor
      stimulus.

PMID- 15470026
TI  - Identification of novel human aggrecan T cell epitopes in HLA-B27 transgenic mice
      associated with spondyloarthropathy.
AB  - The pathology of ankylosing spondylitis, reactive arthritis, and other
      spondyloarthropathies (SpA) is closely associated with the human leukocyte class
      I Ag HLA-B27. A characteristic finding in SpA is inflammation of cartilage
      structures of the joint, in particular at the site of ligament/tendon and bone
      junction (enthesitis). In this study, we investigated the role of CD8+ T cells in
      response to the cartilage proteoglycan aggrecan as a potential candidate
      autoantigen in BALB/c-B27 transgenic mice. We identified four new HLA-B27
      restricted nonamer peptides, one of them (no. 67) with a particularly strong T
      cell immunogenicity. Peptide no. 67 immunization was capable of stimulating HLA
      B27-restricted, CD8+ T cells in BALB/c-B27 transgenic animals, but not in wild
      type BALB/c mice. The peptide was specifically recognized on P815-B27
      transfectants by HLA-B27-restricted CTLs, which were also detectable by HLA
      tetramer staining ex vivo as well as in situ. Most importantly, analysis of the
      joints from peptide no. 67-immunized mice induced typical histological signs of
      SpA. Our data indicate that HLA-B27-restricted epitopes derived from human
      aggrecan are involved in the induction of inflammation (tenosynovitis),
      underlining the importance of HLA-B27 in the pathogenesis of SpA.

PMID- 15470027
TI  - IL-7 gene therapy in aging restores early thymopoiesis without reversing
      involution.
AB  - Thymic involution begins early in life and continues throughout adulthood,
      resulting in a decreased population of naive T cells in the periphery and a
      reduced ability to fight off newly encountered infectious diseases. We have
      previously shown that the first step of thymopoiesis is specifically blocked in
      aging. This block at the DN1 to DN2 transition and the subsequent loss of thymic
      output in old age mirrors the changes seen in IL-7-deficient mice, and it is
      hypothesized that decreased intrathymic IL-7 is involved in age-related thymic
      involution. To separate the effect of IL-7 on thymic involution from its function
      as a peripheral lymphocyte growth cofactor, we injected IL-7-secreting stromal
      cells into the thymi of recipient mice. The increased local concentration of IL-7
      maintained the first step of thymopoiesis at a level far higher than was seen in
      age-matched controls. However, despite this success, there was no decrease in
      thymic involution or increase in T cell output. The inability of IL-7 to prevent
      involution led us to the discovery of an additional age-sensitive step in
      thymopoiesis, proliferation of the DN4 population, which is unaffected by IL-7
      expression.

PMID- 15470028
TI  - Flt3-ligand, IL-4, GM-CSF, and adherence-mediated isolation of murine lung
      dendritic cells: assessment of isolation technique on phenotype and function.
AB  - Lung dendritic cells (DCs) are difficult to study due to their limited quantities
      and the complexities required for isolation. Although many procedures have been
      used to overcome this challenge, the effects of isolation techniques on lung DCs
      have not been reported. The current study shows that freshly isolated DCs
      (CD11c+) have limited ability to induce proliferation in allogeneic T cells, and
      are immature as indicated by low cell surface expression of costimulatory
      molecules compared with liver or splenic DCs. DCs isolated after overnight
      culture or from mice treated with Flt3L are phenotypically mature and potent
      stimulators of allogeneic T cells. DCs could not be propagated from lung
      mononuclear cells in response to IL-4 and GM-CSF. Contrary to data reported for
      nonpulmonary DCs, expression of CCR6 was decreased on mature lung DCs, and only a
      subset of mature DCs expressed higher levels of CCR7. Absence of CD8alpha
      expression indicates that freshly isolated DCs are myeloid-type, whereas mature
      DCs induced by overnight culture are both "lymphoid" (CD8alpha+) and "myeloid"
      (CD8alpha-). DCs from mice genetically deficient in CD8alpha expression were
      strong simulators of allogeneic T cells which was consistent with data showing
      that CD8alpha- DCs from CD8alpha-sufficient mice are better APCs compared with
      CD8alpha+ DCs from the same mice. These data show that freshly isolated lung DCs
      are phenotypically and functionally distinct, and that the isolation technique
      alters the biology of these cells. Therefore, lung DC phenotype and function must
      be interpreted relative to the technique used for isolation.

PMID- 15470029
TI  - Regression of established liver tumor induced by monoepitopic peptide-based
      immunotherapy.
AB  - Most types of cancer are difficult to eradicate, and some, like hepatocellular
      carcinoma, are almost always fatal. Among various interventions to improve the
      survival of patients with cancer, immunotherapy seems to hold some promises.
      However, it requires relevant animal models for preclinical development. In this
      study we report a new and relevant experimental model where liver tumors grow
      inside a nontumoral parenchyma of adult mice. This model is based on the
      intrasplenic injection in syngeneic recipient mice of hepatocytes from transgenic
      mice expressing SV40 large T oncogene specifically in the liver. Using this model
      where no apparent spontaneous cellular immune response was observed, immunization
      using a single injection of monoepitopic SV40 T Ag short peptide was sufficient
      to provoke liver tumor destruction, leading rapidly to complete remission. Tumor
      regression was associated with the induction of a long-lasting CD8+ T cell
      response, observed not only in the spleen but also, more importantly, in the
      tumoral liver. These results show the efficacy of peptide immunotherapy in the
      treatment of liver cancer.

PMID- 15470030
TI  - Initiation of cellular organization in lymph nodes is regulated by non-B cell
      derived signals and is not dependent on CXC chemokine ligand 13.
AB  - The molecular and cellular events that initiate the formation of T and B cell
      areas in developing lymph nodes are poorly understood. In this study we show that
      formation of the lymphoid architecture in murine neonatal lymph nodes evolves
      through a series of distinct stages. The initial segregation of T and B cells is
      regulated in a CXCL13-independent manner, characterized by the localization of B
      cells in a ring-like pattern in the outer cortex on day 4. However, during this
      CXCL13-independent phase of lymph node modeling, CXCL13 is expressed and
      regulated in a lymphotoxin-alpha1beta2 (LTalpha1beta2)-dependent manner.
      Surprisingly, neonatal B cells are unable to respond to this chemokine and also
      lack surface LTalpha1beta2 expression. At this time, CD45+CD4+CD3- cells are the
      predominant LTalpha1beta2-expressing cells and are also capable of responding to
      CXCL13. From day 4 on, architectural changes become CXCL13 dependent, and B cells
      become fully CXCL13 responsive, express LTalpha1beta2, and cluster in
      anatomically distinct follicles. Because the initial induction of CXCL13 is
      dependent on LTalpha1beta2, a role for CD45+CD4+CD3- cells in inducing chemokine
      expression in the developing lymph nodes is proposed and, as such, a role in
      initiation of the shaping of the microenvironment.

PMID- 15470031
TI  - Human cytomegalovirus induces inhibition of macrophage differentiation by binding
      to human aminopeptidase N/CD13.
AB  - Human CMV (HCMV) infection in immunocompromised patients is frequently associated
      with impaired immunological functions. We have recently found that HCMV inhibits
      cytokine-induced differentiation of monocytes into macrophages. In this study, we
      demonstrate that HCMV-induced inhibition of macrophage differentiation was
      dependent on binding of virus particles to the cell surface molecule
      CD13/aminopeptidase N, which involved Ca2+ -dependent intracellular signaling
      pathways. We found that treatment of cells with the CD13-specific mAbs My7 and
      WM15 inhibited macrophage differentiation, and that My7 and WM15 induced a rise
      in intracellular Ca2+ in similar ways as HCMV. In contrast, binding of the CD13
      specific Ab clone SJ1D1 blocked the ability of HCMV to inhibit macrophage
      differentiation, and blocked the HCMV-induced intracellular Ca2+ response. In
      addition, the Ca2+ modulator thapsigargin partially blocked the ability of HCMV
      to inhibit cellular differentiation. Furthermore, we demonstrate that recombinant
      viral glycoprotein gB was able to inhibit macrophage differentiation in similar
      ways as the virus. Thus, these results suggest that binding of HCMV to monocytes
      induces an intracellular rise of Ca2+, of which one result is a block in the
      ability of the cells to differentiate into macrophages. These observations
      suggest an efficient viral strategy to interfere with cellular differentiation
      pathways, and may also in part explain the generalized immunosuppression that is
      often observed in HCMV-infected patients.

PMID- 15470032
TI  - E2f1 mutation induces early onset of diabetes and Sjogren's syndrome in nonobese
      diabetic mice.
AB  - E2f1 is an important regulator of T cell proliferation, differentiation, and
      apoptosis that controls the transcription of a group of genes that are normally
      regulated at the G1 to S phase transition in the cell cycle. Insulin-dependent
      diabetes mellitus (IDDM) and Sjogren's syndrome (SS) are highly regulated
      autoimmune diseases that develop spontaneously in NOD mice. The aim of the
      present in vivo study was to explore the functional importance of the E2f1
      molecule in IDDM and SS, in the context of whole animal physiology and
      pathophysiology, using E2f1-deficient NOD mice. For the experiment, we produced
      NOD mice homozygous for a nonfunctional E2f1 allele onto a NOD background. E2f1
      deficient NOD mice developed an early and increased onset of diabetes as compared
      with their littermates. These mice also exhibited a defect in T lymphocyte
      development, leading to excessive numbers of mature T cells (CD4+ and CD8+), due
      to a maturation stage-specific defect in the apoptosis of thymocytes and
      peripheral T cells. We also found that they also exhibited a more rapid and
      increased entry into the S phase following antigenic stimulation of spleen cells
      and thymocytes in vitro. Furthermore, E2f1-deficient mice showed a profound
      decrease of immunoregulatory CD4+CD25+ T cells, while the spleen cells of NOD
      mice lacking E2f1 showed a significant increase of the proinflammatory cytokine
      IFN-gamma following antigenic stimulation in vitro. Consistent with these
      observations, E2f1 homozygous mutant NOD mice were highly predisposed to the
      development of IDDM and SS.

PMID- 15470033
TI  - Blocking programmed death-1 ligand-PD-1 interactions by local gene therapy
      results in enhancement of antitumor effect of secondary lymphoid tissue
      chemokine.
AB  - The negative signal provided by interactions of programmed death-1 (PD-1) and its
      ligands, costimulatory molecules PD-L1 (also B7-H1) and PD-L2 (also B7-DC), is
      involved in the mechanisms of tumor immune evasion. In this study, we found that
      this negative signal was also involved in immune evasion in tumor immunotherapy.
      When we used different doses of a constructed eukaryotic expression plasmid,
      pSLC, which expresses functional murine secondary lymphoid tissue chemokine (SLC,
      CCL21), to treat BALB/c mice inoculated with H22 murine hepatoma cells, the
      inhibitory effect was enhanced along with the increase of pSLC dosage.
      Unexpectedly, however, the best complete inhibition rate of tumor was reached
      when pSLC was used at the dosage of 50 microg but not 100 or 200 microg. RT-PCR
      and real-time PCR revealed that both PD-L1 and PD-L2 genes were expressed in
      tumor and vicinal muscle tissues of tumor-bearing mice and the expression level
      was significantly increased if a higher dosage of pSLC was administered. We then
      constructed a eukaryotic expression plasmid (pPD-1A) that expresses the
      extracellular domain of murine PD-1 (sPD-1). sPD-1 could bind PD-1 ligands, block
      PD-Ls-PD-1 interactions, and enhance the cytotoxicity of tumor-specific CTL.
      Local gene transfer by injection of pPD-1A mediated antitumor effect and improved
      SLC-mediated antitumor immunity. The combined gene therapy with SLC plus sPD-1
      did not induce remarkable autoimmune manifestations. Our findings provide a
      potent method of improving the antitumor effects of SLC and possibly other
      immunotherapeutic methods by local blockade of negative costimulatory molecules.

PMID- 15470034
TI  - MIP-3alpha transfection into a rodent tumor cell line increases intratumoral
      dendritic cell infiltration but enhances (facilitates) tumor growth and decreases
      immunogenicity.
AB  - Dendritic cells are powerful APCs for activation of specific antitumor T
      lymphocytes. To present tumor Ags efficiently, they have first to migrate to the
      tumor site, engulf Ag, and then process them. To attract immature DCs to the
      tumor site, we transfected tumor cells with MIP-3alpha which is strongly
      chemotactic for DCs. Surprisingly, MIP-3alpha-transfected tumor cells grew faster
      than the mock-transfected tumor cells. Histological analysis and tumor
      dissociation confirmed that the MIP-3alpha-transfected tumors contain three to
      four times more DCs than mock-transfected tumors. FACS analysis of the intratumor
      DCs showed that they were predominantly immature. Functional analysis showed that
      the alloreactivity mediated by these infiltrating MIP-3alpha-transfected tumor
      DCs is strongly reduced. In conclusion, MIP-3alpha is an efficient chemokine for
      attracting DCs in vivo, but the high density of DCs in the tumor site injection
      is not a sufficient condition to induce an immune response. Furthermore, this
      attraction of immature DCs may always have an adverse effect by inducing a
      tolerance to the tumor cells.

PMID- 15470035
TI  - Geranylgeraniol regulates negatively caspase-1 autoprocessing: implication in the
      Th1 response against Mycobacterium tuberculosis.
AB  - Caspase-1 is a cysteine protease composed by two 20-kDa and two 10-kDa subunits
      that processes pro-IL-1beta and pro-IL-18 to their mature forms. This enzyme is
      present in cells as a latent zymogen that becomes active through a tightly
      regulated proteolytic cascade. Activation is initiated by the oligomerization of
      an adaptor molecule, or by the formation of a multiprotein complex named
      inflammasome. Negative regulation of caspase-1 activation is exerted by proteins
      that compete with the adaptor molecule or with the inflammasome formation. We
      previously reported that fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase, increases caspase-1 activity in PBMC. This effect was
      strengthened by Mycobacterium tuberculosis, rending an exacerbated IL-1beta, IL
      18, and IFN-gamma production. Mevalonate, the product of 3-hydroxy-3
      methylglutaryl coenzyme A reductase, is a precursor for both nonsterol isoprenoid
      and sterol formation. In this study, we studied the involvement of mevalonate
      derivatives in the regulation of caspase-1 activation. Inhibition of sterol
      formation by SKF-104976 or haloperidol had no effect on IL-1beta release.
      However, the isoprenoid geranylgeraniol prevented both caspase-1 activation and
      the exacerbated IL production induced by fluvastatin. This isoprenoid
      significantly reduced the release of IL-18 and IFN-gamma by PBMC treated with
      mycobacteria, even in the absence of fluvastatin. In correlation with the
      increased caspase-1 activity, fluvastatin stimulated the proforms cleavage,
      enhancing the formation of active subunit p10. Geranylgeraniol not only prevented
      this effect, but induced proforms accumulation. Present results suggest that,
      once the proteolytic cascade is initiated, geranylgeraniol may exert an
      additional negative regulation on caspase-1 cleavage process.

PMID- 15470036
TI  - Restriction of de novo nucleotide biosynthesis interferes with clonal expansion
      and differentiation into effector and memory CD8 T cells.
AB  - Nucleotide synthesis inhibitors are currently used in neoplastic diseases or as
      immunosuppressive agents for the prevention of acute rejection in organ
      transplantation and the treatment of autoimmune disorders. We have previously
      described that these inhibitors interfere with proliferation and survival of
      primary T cells in vitro. However, the precise effects of nucleotide restriction
      on effector and memory functions have not been elucidated. In this study, we
      investigated the impact of nucleotide synthesis inhibition on CD8 T cell
      differentiation by using TCR transgenic mice (F5) specific for the influenza
      virus nucleoprotein 68 peptide presented on the H-2Db molecule. Our results show
      that methotrexate and 5-fluorouracil prevent the acquisition of effector
      functions, such as IFN-gamma, granzyme B expression, and cytotoxic function
      following antigenic stimulation of naive cells. Surprisingly, in the presence of
      mycophenolate mofetil, activated F5 cells are still able to produce granzyme B
      and to kill target cells but to a lesser extent compared with control. All three
      inhibitors interfere with the differentiation of naive cells into memory CD8 T
      cells. In contrast, the drugs are unable to inhibit the development of improved
      cytotoxic functions displayed by memory CD8 T cells.

PMID- 15470037
TI  - The magnitude of Akt/phosphatidylinositol 3'-kinase proliferating signaling is
      related to CD45 expression in human myeloma cells.
AB  - In multiple myeloma, the Akt/PI3K pathway is involved in the proliferation of
      myeloma cells. In the current study, we have investigated the impact of the CD45
      phosphatase in the control of Akt/PI3K activation. We show that Akt activation in
      response to insulin-like growth factor-1 (IGF-1) is highly variable from one
      human myeloma cell line to another one. Actually, Akt activation is highly
      related to whether CD45 is expressed or not. Indeed, both the magnitude and the
      duration of Akt phosphorylation in response to IGF-1 are more important in CD45-
      than in CD45+ myeloma cell lines. We next demonstrate a physical association
      between CD45 and IGF-1 receptor (IGF-1R) suggesting that CD45 could be involved
      in the dephosphorylation of the IGF-1R. Furthermore, the growth of CD45- myeloma
      cell lines is mainly or even totally controlled by the PI3K pathway whereas that
      of CD45+ myeloma cell lines is modestly controlled by it. Indeed, wortmannin, a
      specific PI3K inhibitor, induced a dramatic growth inhibition in the CD45-
      myeloma cell lines characterized by a G1 growth arrest, whereas it has almost no
      effect on CD45+ myeloma cell lines. Altogether, these results suggest that CD45
      negatively regulates IGF-1-dependent activation of PI3K. Thus, strategies that
      block IGF-1R signaling and consequently the Akt/PI3K pathway could be a priority
      in the treatment of patients with multiple myeloma, especially those lacking CD45
      expression that have a very poor clinical outcome.

PMID- 15470038
TI  - Granulocyte colony-stimulating factor modulates alpha-galactosylceramide
      responsive human Valpha24+Vbeta11+NKT cells.
AB  - Despite more than a 10-fold increase in T cell numbers in G-CSF-mobilized
      peripheral blood stem cell (PBSC) grafts, incidence and severity of acute graft
      vs-host disease (GVHD) are comparable to bone marrow transplantation. As CD1d
      restricted, Valpha24+Vbeta11+ NKT cells have pivotal immune regulatory functions
      and may influence GVHD, we aimed to determine whether G-CSF has any effects on
      human NKT cells. In this study, we examined the frequency and absolute numbers of
      peripheral blood NKT cells in healthy stem cell donors (n = 8) before and
      following G-CSF (filgrastim) treatment. Effects of in vivo and in vitro G-CSF on
      NKT cell cytokine expression profiles and on responsiveness of NKT cell
      subpopulations to specific stimulation by alpha-galactosylceramide (alpha-GalCer)
      were assessed. Contrary to the effects on conventional T cells, the absolute
      number of peripheral blood NKT cells was unaffected by G-CSF administration.
      Furthermore, responsiveness of NKT cells to alpha-GalCer stimulation was
      significantly decreased (p < 0.05) following exposure to G-CSF in vivo. This
      hyporesponsiveness was predominantly due to a direct effect on NKT cells, with a
      lesser contribution from G-CSF-mediated changes in APC. G-CSF administration
      resulted in polarization of NKT cells toward a Th2, IL-4-secreting phenotype
      following alpha-GalCer stimulation and preferential expansion of the CD4+ NKT
      cell subset. We conclude that G-CSF has previously unrecognized differential
      effects in vivo on NKT cells and conventional MHC-restricted T cells, and effects
      on NKT cells may contribute to the lower than expected incidence of GVHD
      following allogeneic peripheral blood stem cell transplantation.

PMID- 15470039
TI  - STAT6-dependent differentiation and production of IL-5 and IL-13 in murine NK2
      cells.
AB  - NK cells differentiate into either NK1 or NK2 cells that produce IFN-gamma or IL
      5 and IL-13, respectively. Little is known, however, about the molecular
      mechanisms that control NK1 and NK2 cell differentiation. To address these
      questions, we established an in vitro mouse NK1/NK2 cell differentiation culture
      system. For NK1/NK2 cell differentiation, initial stimulation with PMA and
      ionomycin was required. The in vitro differentiated NK2 cells produced IL-5 and
      IL-13, but the levels were 20 times lower than those of Th2 or T cytotoxic (Tc)2
      cells. No detectable IL-4 was produced. Freshly prepared NK cells express IL
      2Rbeta, IL-2RgammaC, and IL-4Ralpha. After stimulation with PMA and ionomycin, NK
      cells expressed IL-2Ralpha. NK1 cells displayed higher cytotoxic activity against
      Yac-1 target cells. The levels of GATA3 protein in developing NK2 cells were
      approximately one-sixth of those in Th2 cells. Both NK1 and NK2 cells expressed
      large amounts of repressor of GATA, the levels of which were equivalent to CD8
      Tc1 and Tc2 cells and significantly higher than those in Th2 cells. The levels of
      histone hyperacetylation of the IL-4 and IL-13 gene loci in NK2 cells were very
      low and equivalent to those in naive CD4 T cells. The production of IL-5 and IL
      13 in NK2 cells was found to be STAT6 dependent. Thus, similar to Th2 cells, NK2
      cell development is dependent on STAT6, and the low level expression of GATA3 and
      the high level expression of repressor of GATA may influence the unique type 2
      cytokine production profiles of NK2 cells.

PMID- 15470040
TI  - Essential role of LFA-1 in activating Th2-like responses by alpha
      galactosylceramide-activated NKT cells.
AB  - NKT cells produce large amounts of cytokines associated with both the Th1 (IFN
      gamma) and Th2 (IL-4) responses following stimulation of their invariant Valpha14
      Ag receptor. The role of adhesion molecules in the activation of NKT cells by the
      Valpha14 ligand alpha-galactosylceramide (alpha-GalCer) remains unclear. To
      address this issue, LFA-1-/- (CD11a-/-) mice were used to investigate IL-4 and
      IFN-gamma production by NKT cells following alpha-GalCer stimulation.
      Intriguingly, LFA-1-/- mice showed increased IL-4, IL-5, and IL-13 production and
      polarized Th2-type responses in response to alpha-GalCer in vitro and in vivo.
      Furthermore, the Th2-specific transcription factor GATA-3 was up-regulated in
      alpha-GalCer-activated NKT cells from LFA-1-/- mice. These results provide the
      first genetic evidence that the adhesion receptor LFA-1 has a crucial role in Th2
      polarizing functions of NKT cells.

PMID- 15470041
TI  - Rac1 mediates collapse of microvilli on chemokine-activated T lymphocytes.
AB  - Lymphocytes circulate in the blood and upon chemokine activation rapidly bind,
      where needed, to microvasculature to mediate immune surveillance. Resorption of
      microvilli is an early morphological alteration induced by chemokines that
      facilitates lymphocyte emigration. However, the antecedent molecular mechanisms
      remain largely undefined. We demonstrate that Rac1 plays a fundamental role in
      chemokine-induced microvillar breakdown in human T lymphocytes. The supporting
      evidence includes: first, chemokine induces Rac1 activation within 5 s via a
      signaling pathway that involves Galphai. Second, constitutively active Rac1
      mediates microvilli disintegration. Third, blocking Rac1 function by cell
      permeant C-terminal "Trojan" peptides corresponding to Rac1 (but not Rac2, Rho,
      or Cdc42) blocks microvillar loss induced by the chemokine stromal cell-derived
      factor 1alpha (SDF-1alpha). Furthermore, we demonstrate that the molecular
      mechanism of Rac1 action involves dephosphorylation-induced inactivation of the
      ezrin/radixin/moesin (ERM) family of actin regulators; such inactivation is known
      to detach the membrane from the underlying actin cytoskeleton, thereby
      facilitating disassembly of actin-based peripheral processes. Specifically, ERM
      dephosphorylation is induced by constitutively active Rac1 and stromal cell
      derived factor 1alpha-induced ERM dephosphorylation is blocked by either the
      dominant negative Rac1 construct or by Rac1 C-terminal peptides. Importantly, the
      basic residues at the C terminus of Rac1 are critical to Rac1's participation in
      ERM dephosphorylation and in microvillar retraction. Together, these data
      elucidate new roles for Rac1 in early signal transduction and cytoskeletal
      rearrangement of T lymphocytes responding to chemokine.

PMID- 15470042
TI  - Murine CD4+CD25+ regulatory T cells fail to undergo chromatin remodeling across
      the proximal promoter region of the IL-2 gene.
AB  - CD4+CD25+ regulatory T cells (Treg) acquire unique immunosuppressive properties
      while maintaining an anergy phenotype when activated in vitro under conditions
      that induce IL-2 production and proliferation in conventional CD4+ T cells. We
      investigated the mechanism underlying one component of this naturally anergic
      phenotype, the inability of the Treg cells to produce IL-2 following activation.
      Analysis of freshly isolated murine CD4+CD25+ Treg and conventional CD4+CD25- T
      cells following PMA/ionomycin stimulation demonstrated no differences in
      inducible AP-1 formation, an important transcriptional complex in regulating IL-2
      gene expression. Although p38 MAPK and ERK1/2 protein kinases were phosphorylated
      with similar kinetics, we observed diminished activation of JNK in the CD4+CD25+
      Treg cells. However, lentiviral-mediated reconstitution of the JNK pathway using
      a constitutively active construct did not overcome the block in IL-2 synthesis.
      Using a PCR-based chromatin accessibility assay we found that the minimal IL-2
      promoter region of CD4+CD25+ Treg cells, unlike conventional CD4 T cells, did not
      undergo chromatin remodeling following stimulation, suggesting that the inability
      of CD4+CD25+ Treg cells to secrete IL-2 following activation is controlled at the
      chromatin level.

PMID- 15470043
TI  - Suppressive oligodeoxynucleotides inhibit Th1 differentiation by blocking IFN
      gamma- and IL-12-mediated signaling.
AB  - Repetitive TTAGGG motifs present at high frequency in mammalian telomeres can
      suppress Th1-mediated immune responses. Synthetic oligonucleotides (ODN)
      containing TTAGGG motifs mimic this activity and have proven effective in the
      prevention/treatment of certain Th1-dependent autoimmune diseases. This work
      explores the mechanism by which suppressive ODN block the induction of Th1
      immunity. Findings indicate that these ODN inhibit IFN-gamma-induced STAT1
      phosphorylation and IL-12-induced STAT3 and STAT4 phosphorylation. As a result, T
      bet expression is reduced as is the maturation of naive CD4+ cells into Th1
      effectors. These changes indirectly support the generation of Th2-dominated
      immune responses. Suppressive ODN may thus represent a novel approach to
      influence the Th1:Th2 balance in vivo.

PMID- 15470045
TI  - Reversal in the immunodominance hierarchy in secondary CD8+ T cell responses to
      influenza A virus: roles for cross-presentation and lysis-independent
      immunodomination.
AB  - Immunodominance is a central feature of CD8+ T cell (TCD8+) responses to
      pathogens, transplants, and tumors. Determinants occupy a stable position in an
      immunodominance hierarchy (alpha-, beta-, etc.) defined by the frequencies of
      responding TCD8+. In this paper, we study the mechanistic basis for place
      swapping between alpha- (acid polymerase (PA)(224-233)) and beta-determinants
      (nuclear protein 366-374) in primary vs secondary anti-influenza A virus (IAV)
      responses in mice. This phenomena was recently correlated with the inability of
      IAV-infected nondendritic cells (DCs) to generate PA(224-233), and it was
      proposed that secondary TCD8+ are principally activated by IAV-infected
      epithelial cells, while primary TCD8+ are activated by IAV-infected DCs. In this
      study, we show that the inability of non-DCs to generate PA(224-232) is relative
      rather than absolute, and that the preferential use of cross-priming in secondary
      anti-IAV responses can also account for the revised hierarchy. We further show
      that immunodomination of PA(224-233)-specific TCD8+ by nucleoprotein 366-374
      specific TCD8+ plays a critical role in the phenomena, and that this is unlikely
      to be mediated by TCD8+ lysis of APCs or other cells.

PMID- 15470044
TI  - Engagement of glucocorticoid-induced TNFR family-related receptor on effector T
      cells by its ligand mediates resistance to suppression by CD4+CD25+ T cells.
AB  - Nonactivated CD4+CD25+ regulatory T cells constitutively express glucocorticoid
      induced TNFR family-related receptor (GITR), a TNFR family member whose
      engagement was presumed to abrogate regulatory T cell-mediated suppression. Using
      GITR-/- mice, we report that GITR engagement on CD25-, not CD25+ T cells
      abrogates T cell-mediated suppression. Mouse APCs constitutively express GITR
      ligand (GITR-L), which is down-regulated following TLR signaling in vivo.
      Although GITR-/-CD25- T cells were capable of mounting proliferative responses,
      they were incapable of proliferation in the presence of physiological numbers of
      CD25+ T cells. Thus, GITR-L provides an important signal for CD25- T cells,
      rendering them resistant to CD25+ -mediated regulation at the initiation of the
      immune response. The down-regulation of GITR-L by inflammatory stimuli may
      enhance the susceptibility of effector T cells to suppressor activity during the
      course of an infectious insult.

PMID- 15470046
TI  - Role of B7 in T cell tolerance.
AB  - The induction of effective immune responses requires costimulation by B7
      molecules, and Ag recognition without B7 is thought to result in no response or
      tolerance. We compared T cell responses in vivo to the same Ag presented either
      by mature dendritic cells (DCs) or as self, in the presence or absence of B7. We
      show that Ag presentation by mature B7-1/2-deficient DCs fails to elicit an
      effector T cell response but does not induce tolerance. In contrast, using a
      newly developed adoptive transfer system, we show that naive OVA-specific DO11
      CD4+ T cells become anergic upon encounter with a soluble form of OVA, in the
      presence or absence of B7. However, tolerance in DO11 cells transferred into
      soluble OVA transgenic recipients can be broken by immunization with Ag-pulsed
      DCs only in B7-deficient mice and not in wild-type mice, suggesting a role of B7
      in maintaining tolerance in the presence of strong immunogenic signals. Comparing
      two double-transgenic models--expressing either a soluble or a tissue Ag--we
      further show that B7 is not only essential for the active induction of regulatory
      T cells in the thymus, but also for their maintenance in the periphery. Thus, the
      obligatory role of B7 molecules paradoxically is to promote effective T cell
      priming and contain effector responses when self-Ags are presented as foreign.

PMID- 15470047
TI  - Loss of SHIP and CIS recruitment to the granulocyte colony-stimulating factor
      receptor contribute to hyperproliferative responses in severe congenital
      neutropenia/acute myelogenous leukemia.
AB  - Mutations in the G-CSF receptor (G-CSFR) in patients with severe congenital
      neutropenia (SCN) are postulated to contribute to transformation to acute
      myelogenous leukemia (AML). These mutations result in defective receptor
      internalization and sustained cellular activation, suggesting a loss of negative
      signaling by the G-CSFR. In this paper we investigated the roles of SHIP and
      cytokine-inducible Src homology 2 protein (CIS) in down-modulating G-CSFR signals
      and demonstrate that loss of their recruitment as a consequence of receptor
      mutations leads to aberrant signaling. We show that SHIP binds to phosphopeptides
      corresponding to Tyr744 and Tyr764 in the G-CSFR and that Tyr764 is required for
      in vivo phosphorylation of SHIP and the formation of SHIP/Shc complexes. Cells
      expressing a G-CSFR form lacking Tyr764 exhibited hypersensitivity to G-CSF and
      enhanced proliferation, but to a lesser degree than observed with the most common
      mutant G-CSFR form in patients with SCN/AML, prompting us to investigate whether
      suppressor of cytokine signaling proteins also down-modulate G-CSFR signals. G
      CSF was found to induce the expression of CIS and of CIS bound to phosphopeptides
      corresponding to Tyr729 and Tyr744 of the G-CSFR. The expression of CIS was
      prolonged in cells with the SCN/AML mutant G-CSFR lacking Tyr729 and Tyr744,
      which also correlated with increased G-CSFR expression. These findings suggest
      that SHIP and CIS interact with distal phosphotyrosine residues in the G-CSFR to
      negatively regulate G-CSFR signaling by limiting proliferation and modulating
      surface expression of the G-CSFR, respectively. Novel therapeutic approaches
      targeting inhibitory pathways that limit G-CSFR signaling may have promise in the
      treatment of patients with SCN/AML.

PMID- 15470048
TI  - Sonic hedgehog regulates early human thymocyte differentiation by counteracting
      the IL-7-induced development of CD34+ precursor cells.
AB  - The Hedgehog (Hh) family of signaling molecules normally functions in the
      development of numerous tissues by regulating cellular differentiation and
      proliferation. Recent results have demonstrated that the different components of
      the Hh signaling pathway are expressed in the human thymus. In this study, we
      investigate the potential role of Sonic hedgehog (Shh) in human intrathymic T
      cell maturation. Results show that the expression of the two components of the Hh
      receptor, Patched and Smoothened, is mostly restricted to CD34+ precursor cells
      that are committing to the T cell lineage. Shh significantly increased the
      viability of CD34+ T cell precursors modulating bcl-2 and bax protein expression,
      and also inhibited their proliferation. The treatment of chimeric human-mouse
      fetal thymus organ cultures with Shh resulted in an arrested thymocyte
      differentiation and an accumulation of CD34+ progenitor cells. This effect was
      mainly attributed to the ability of Shh to counteract the IL-7-induced
      proliferation and differentiation of CD34+ cells. Shh down-regulated in the
      precursor cell population the expression of IL-7R as well as stromal-derived
      factor-1 chemokine receptor, CXCR4, and inhibited IL-7-dependent STAT5
      phosphorylation. Therefore, Shh may function as a maintenance factor for
      intrathymic CD34+ precursor cells.

PMID- 15470049
TI  - Developmental activation of the TCR alpha enhancer requires functional
      collaboration among proteins bound inside and outside the core enhancer.
AB  - The TCR delta enhancer (Edelta) and TCR alpha enhancer (Ealpha) play critical
      roles in the temporal and lineage-specific control of V(D)J recombination and
      transcription at the TCR alphadelta locus, working as a developmental switch
      controlling a transition from TCR delta to TCR alpha activity during thymocyte
      development. Previous experiments using a transgenic reporter substrate revealed
      that substitution of the 116-bp minimal Ealpha, denoted Talpha1-Talpha2, for the
      entire 1.4-kb Ealpha led to a premature activation of V(D)J recombination. This
      suggested that binding sites outside of Talpha1-Talpha2 are critical for the
      strict developmental regulation of TCR alpha rearrangement. We have further
      analyzed Ealpha to better understand the mechanisms responsible for appropriate
      developmental regulation in vivo. We found that a 275-bp Ealpha fragment, denoted
      Talpha1-Talpha4, contains all binding sites required for proper developmental
      regulation in vivo. This suggests that developmentally appropriate enhancer
      activation results from a functional interaction between factors bound to Talpha1
      Talpha2 and Talpha3-Talpha4. In support of this, EMSAs reveal the formation of a
      large enhanceosome complex that reflects the cooperative assembly of proteins
      bound to both Talpha1-Talpha2 and Talpha3-Talpha4. Our data suggest that
      enhanceosome assembly is critical for developmentally appropriate activation of
      Ealpha in vivo, and that transcription factors, Sp1 and pCREB, may play unique
      roles in this process.

PMID- 15470050
TI  - Identification of seventeen new simian immunodeficiency virus-derived CD8+ T cell
      epitopes restricted by the high frequency molecule, Mamu-A*02, and potential
      escape from CTL recognition.
AB  - MHC class I-restricted CD8+ T cells play an important role in controlling HIV and
      SIV replication. In SIV-infected Indian rhesus macaques (Macaca mulatta),
      comprehensive CD8+ T cell epitope identification has only been undertaken for two
      alleles, Mamu-A*01 and Mamu-B*17. As a result, these two molecules account for
      virtually all known MHC class I-restricted SIV-derived CD8+ T cell epitopes. SIV
      pathogenesis research and vaccine testing have intensified the demand for
      epitopes restricted by additional MHC class I alleles due to the shortage of Mamu
      A*01+ animals. Mamu-A*02 is a high frequency allele present in over 20% of
      macaques. In this study, we characterized the peptide binding of Mamu-A*02 using
      a panel of single amino acid substitution analogues and a library of 497
      unrelated peptides. Of 230 SIVmac239 peptides that fit the Mamu-A*02 peptide
      binding motif, 75 peptides bound Mamu-A*02 with IC50 values of < or = 500 nM. We
      assessed the antigenicity of these 75 peptides using an IFN-gamma ELISPOT assay
      with freshly isolated PBMC from eight Mamu-A*02+ SIV-infected macaques and
      identified 17 new epitopes for Mamu-A*02. The synthesis of five Mamu-A*02
      tetramers demonstrated the discrepancy between tetramer binding and IFN-gamma
      secretion by SIV-specific CD8+ T cells during chronic SIV infection. Bulk
      sequencing determined that 2 of the 17 epitopes accumulated amino acid
      replacements in SIV-infected macaques by the chronic phase of infection,
      suggestive of CD8+ T cell escape in vivo. This work enhances the use of the SIV
      infected macaque model for HIV and increases our understanding of the breadth of
      CD8+ T cell responses in SIV infection.

PMID- 15470051
TI  - Caspase inhibition blocks human T cell proliferation by suppressing appropriate
      regulation of IL-2, CD25, and cell cycle-associated proteins.
AB  - Caspases have been described as proteases essential for the release of certain
      cytokines and for initiation as well as execution of apoptosis. Increasing
      evidence indicates, however, that caspase activity is also required for
      activation-induced proliferation of mature T lymphocytes. The molecular
      mechanism, how caspase activity facilitates T cell proliferation, is still
      controversially discussed. In this study, we show that proliferation of human T
      cells in response to a specific antigenic stimulus is completely prevented by
      caspase inhibition. In addition, we demonstrate that this lack of proliferation
      is due to a failure to initiate cell cycle progression, but not the result of
      increased T cell death. Our results demonstrate that caspase inhibition leads to
      strongly reduced IL-2 release, failure to up-regulate CD25, and a lack of proper
      regulation of cell cycle-associated proteins. Furthermore, T cell proliferation
      was partially rescued by addition of exogenous IL-2. Using Jurkat cells, we show
      that in the absence of caspase-8, the mitogen-induced activation of the
      transcription factor NF-kappaB is moderately diminished, while the activity of
      the composite element CD28 response element and NF-IL-2B AP-1 sites is strongly
      reduced. Finally, we provide evidence that caspase inhibition suppresses the
      activation of purified monocytes by bacterial Ags.

PMID- 15470052
TI  - Linker for activation of T cells integrates positive and negative signaling in
      mast cells.
AB  - The transmembrane adapter linker for activation of T cells (LAT) is thought to
      couple immunoreceptors to intracellular signaling pathways. In mice, its
      intracytoplasmic domain contains nine tyrosines which, when phosphorylated upon
      receptor aggregation, recruit Src-homology 2 domain-containing cytosolic enzymes
      and adapters. The four distal tyrosines are critical for both TCR and FcepsilonRI
      signaling. Unexpectedly, knock-in mice expressing LAT with a point mutation of
      the first or of the last three of these tyrosines exhibited an abnormal T cell
      development characterized by a massive expansion of TH2-like alphabeta or
      gammadelta T cells, respectively. This phenotype suggests that, besides positive
      signals, LAT might support negative signals that normally regulate terminal T
      cell differentiation and proliferation. We investigated here whether LAT might
      similarly regulate mast cell activation, by generating not only positive but also
      negative signals, following FcR engagement. To this end, we examined IgE- and/or
      IgG-induced secretory and intracellular responses of mast cells derived from
      knock-in mice expressing LAT with combinations of tyrosine mutations (Y136F,
      Y(175, 195, 235)F, or Y(136, 175, 195, 235)F). A systematic comparison of pairs
      of mutants enabled us to dissect the respective roles played by the five proximal
      and the four distal tyrosines. We found that LAT tyrosines differentially
      contribute to exocytosis and cytokine secretion and differentially regulate
      biological responses of mucosal- and serosal-type mast cells. We also found that,
      indeed, both positive and negative signals may emanate from distinct tyrosines in
      LAT, whose integration modulates mast cell secretory responses.

PMID- 15470053
TI  - Novel negative regulator of expression in Fas ligand (CD178) cytoplasmic tail:
      evidence for translational regulation and against Fas ligand retention in
      secretory lysosomes.
AB  - Fas ligand ((FasL) CD178), a type II transmembrane protein, induces apoptosis of
      cells expressing the Fas receptor. It possesses a unique cytoplasmic tail
      (FasLCyt) of 80 aa. As a type II transmembrane protein, the early synthesis of
      FasLCyt could affect FasL translation by impacting FasL endoplasmic reticulum
      translocation and/or endoplasmic reticulum retention. Previous studies suggest
      that the proline-rich domain (aa 43-70) in FasLCyt (FasLPRD) inhibits FasL
      membrane expression by retaining FasL in the secretory lysosomes. This report
      shows that deletion of aa 2-33 of FasLCyt dramatically increased total FasL
      levels and FasL cell surface expression. This negative regulator of FasL
      expression is dominant despite the presence of FasLPRD. In addition, retention of
      proline-rich domain-containing FasL in the cytoplasm was not observed. Moreover,
      we demonstrated that FasLCyt regulates FasL expression by controlling the rate of
      de novo synthesis of FasL. Our study demonstrated a novel negative regulator of
      FasL expression in the FasLCyt region and its mechanism of action.

PMID- 15470054
TI  - In vivo adjuvant-induced mobilization and maturation of gut dendritic cells after
      oral administration of cholera toxin.
AB  - Although dendritic cells (DCs) regulate immune responses, they exhibit functional
      heterogeneity depending on their anatomical location. We examined the functional
      properties of intestinal DCs after oral administration of cholera toxin (CT), the
      most potent mucosal adjuvant. Two CD11c+ DC subsets were identified both in
      Peyer's patches and mesenteric lymph nodes (MLN) based on the expression of
      CD8alpha (CD8+ and CD8- DCs, respectively). A third subset of CD11c+CD8int was
      found exclusively in MLN. Feeding mice with CT induced a rapid and transient
      mobilization of a new CD11c+CD8- DC subset near the intestinal epithelium. This
      recruitment was associated with an increased production of the chemokine CCL20 in
      the small intestine and was followed by a massive accumulation of CD8int DCs in
      MLN. MLN DCs from CT-treated mice were more potent activators of naive T cells
      than DCs from control mice and induced a Th2 response. This increase in
      immunostimulating properties was accounted for by CD8int and CD8- DCs, whereas
      CD8+ DCs remained insensitive to CT treatment. Consistently, the CD8int and CD8-
      subsets expressed higher levels of costimulatory molecules than CD8+ and
      corresponding control DCs. Adoptive transfer experiments showed that these two DC
      subsets, unlike CD8+ DCs, were able to present Ags orally coadministered with CT
      in an immunostimulating manner. The ability of CT to mobilize immature DCs in the
      intestinal epithelium and to promote their emigration and differentiation in
      draining lymph nodes may explain the exceptional adjuvant properties of this
      toxin on mucosal immune responses.

PMID- 15470055
TI  - The host resistance locus sst1 controls innate immunity to Listeria monocytogenes
      infection in immunodeficient mice.
AB  - Epidemiological, clinical, and experimental approaches have convincingly
      demonstrated that host resistance to infection with intracellular pathogens is
      significantly influenced by genetic polymorphisms. Using a mouse model of
      infection with virulent Mycobacterium tuberculosis (MTB), we have previously
      identified the sst1 locus as a genetic determinant of host resistance to
      tuberculosis. In this study we demonstrate that susceptibility to another
      intracellular pathogen, Listeria monocytogenes, is also influenced by the sst1
      locus. The contribution of sst1 to anti-listerial immunity is much greater in
      immunodeficient scid mice, indicating that this locus controls innate immunity
      and becomes particularly important when adaptive immunity is significantly
      depressed. Similar to our previous observations using infection with MTB, the
      resistant allele of sst1 prevents formation of necrotic infectious lesions in
      vivo. We have shown that macrophages obtained from sst1-resistant congenic mice
      possess superior ability to kill L. monocytogenes in vitro. The bactericidal
      effect of sst1 is dependent on IFN-gamma activation and reactive oxygen radical
      production by activated macrophages after infection, but is independent of NO
      production. It is possible that there is a single gene that controls common IFN
      dependent macrophage function, which is important in the pathogenesis of
      infections caused by both MTB and L. monocytogenes. However, host resistance to
      the two pathogens may be controlled by two different polymorphic genes encoded
      within the sst1 locus. The polymorphic gene(s) encoded within the sst1 locus that
      controls macrophage interactions with the two intracellular pathogens remains to
      be elucidated.

PMID- 15470056
TI  - The role of CTLs in persistent viral infection: cytolytic gene expression in CD8+
      lymphocytes distinguishes between individuals with a high or low proviral load of
      human T cell lymphotropic virus type 1.
AB  - The proviral load in human T cell lymphotropic virus type 1 (HTLV-1) infection is
      typically constant in each infected host, but varies by >1000-fold between hosts
      and is strongly correlated with the risk of HTLV-1-associated inflammatory
      disease. However, the factors that determine an individual's HTLV-1 proviral load
      remain uncertain. Experimental evidence from studies of host genetics, viral
      genetics, and lymphocyte function and theoretical considerations suggest that a
      major determinant of the equilibrium proviral load is the CD8+ T cell response to
      HTLV-1. In this study, we tested the hypothesis that the gene expression profile
      in circulating CD8+ and CD4+ lymphocytes distinguishes between individuals with a
      low proviral load of HTLV-1 and those with a high proviral load. We show that
      circulating CD8+ lymphocytes from individuals with a low HTLV-1 proviral load
      overexpressed a core group of nine genes with strong functional coherence: eight
      of the nine genes encode granzymes or other proteins involved in cell-mediated
      lysis or Ag recognition. We conclude that successful suppression of the HTLV-1
      proviral load is associated with strong cytotoxic CD8+ lymphocyte activity in the
      peripheral blood.

PMID- 15470057
TI  - Bacterial heat shock proteins enhance class II MHC antigen processing and
      presentation of chaperoned peptides to CD4+ T cells.
AB  - APCs process heat shock protein (HSP):peptide complexes to present HSP-chaperoned
      peptides on class I MHC molecules, but the ability of HSPs to contribute
      chaperoned peptides for class II MHC (MHC-II) Ag processing and presentation is
      unclear. Our studies revealed that exogenous bacterial HSPs (Escherichia coli
      DnaK and Mycobacterium tuberculosis HSP70) delivered an extended OVA peptide for
      processing and MHC-II presentation, as detected by T hybridoma cells. Bacterial
      HSPs enhanced MHC-II presentation only if peptide was complexed to the HSP,
      suggesting that the key HSP function was enhanced delivery or processing of
      chaperoned peptide Ag rather than generalized enhancement of APC function. HSP
      enhanced processing was intact in MyD88 knockout cells, which lack most TLR
      signaling, further suggesting the effect was not due to TLR-induced induction of
      accessory molecules. Bacterial HSPs enhanced uptake of peptide, which may
      contribute to increased MHC-II presentation. In addition, HSPs enhanced binding
      of peptide to MHC-II molecules at pH 5.0 (the pH of vacuolar compartments), but
      not at pH 7.4, indicating another mechanism for enhancement of MHC-II Ag
      processing. Bacterial HSPs are a potential source of microbial peptide Ags during
      phagocytic processing of bacteria during infection and could potentially be
      incorporated in vaccines to enhance presentation of peptides to CD4+ T cells.

PMID- 15470058
TI  - Preapoptotic phenotype of viral epitope-specific CD8 T cells precludes memory
      development and is an intrinsic property of the epitope.
AB  - Virus-specific CD8 T cells after clearance of infection reduce their number in
      lymphoid organs by apoptotic death and by migration into peripheral tissues.
      During and after infection, many lymphocytic choriomeningitis virus (LCMV)
      specific CD8 T cells in lymphoid but not peripheral tissues are in a preapoptotic
      state, as detected by the early apoptosis marker annexin V. In this report, we
      investigated the significance of this preapoptotic state and how it may be
      influenced by viral epitope specificity. Stimulation with anti-CD3 or IL-2 in
      vitro postponed DNA fragmentation in annexin V+ cells, but adoptive transfer
      studies in vivo showed that this preapoptotic phenotype precluded the development
      of functional memory. CD8 T cells specific to LCMV epitopes NP396 and gp33
      differed in their preapoptotic state, with NP396-specific T cells binding more
      annexin V than gp33-specific T cells. These epitope- and tissue-dependent
      differences were seen in primary, memory, and secondary responses and in mice
      receiving different displays of Ag by infection with LCMV strains of different
      tropisms or by infection with vaccinia virus recombinants expressing LCMV
      proteins. Thus, the epitope-dependent differences in apoptosis were independent
      of virus tropisms, duration of Ag exposure, and competition within APCs, and were
      an intrinsic property of the epitope. The tissue-dependent and epitope-dependent
      preapoptotic state correlated with reduced expression of IL-7Ralpha.

PMID- 15470059
TI  - CpG oligodeoxynucleotides stimulate protective innate immunity against pulmonary
      Klebsiella infection.
AB  - Bacterial pneumonia is a leading cause of mortality in the United States. Innate
      immune responses, including type-1 cytokine production, are critical to the
      effective clearance of bacterial pathogens from the lung. Synthetic
      oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotide motifs (CpG
      ODN), which mimic the effects of bacterial DNA, have been shown to enhance type-1
      cytokine responses during infection due to intracellular pathogens, resulting in
      enhanced microbial clearance. The role of CpG ODN in modulating protective innate
      immunity against extracellular pathogens is unknown. Using a murine model of Gram
      negative pneumonia, we found that CpG ODN administration stimulated protective
      immunity against Klebsiella pneumoniae. Specifically, intratracheal (i.t.)
      administration of CpG ODN (30 microg) 48 h before i.t. K. pneumoniae challenge
      resulted in increased survival, compared with animals pretreated with control ODN
      or saline. Pretreatment with CpG ODN resulted in enhanced bacterial clearance in
      lung and blood, and higher numbers of pulmonary neutrophils, NKT cells,
      gammadelta-T cells, and activated NK1.1+ cells and gammadelta-T lymphocytes
      during infection. Furthermore, pretreatment with CpG ODN enhanced the production
      of TNF-alpha, and type-1 cytokines, including IL-12, IFN-gamma, and the IFN-gamma
      dependent ELR- CXC chemokines IFN-gamma-inducible protein-10 and monokine induced
      by IFN-gamma in response to Klebsiella challenge, compared with control mice.
      These findings indicate that i.t. administration of CpG ODN can stimulate
      multiple components of innate immunity in the lung, and may form the basis for
      novel therapies directed at enhancing protective immune responses to severe
      bacterial infections of the lung.

PMID- 15470060
TI  - Vdelta1+ gammadelta T cells producing CC chemokines may bridge a gap between
      neutrophils and macrophages in innate immunity during Escherichia coli infection
      in mice.
AB  - An influx of neutrophils followed a short time later by an influx of macrophages
      to the infected site plays a key role in innate immunity against Escherichia coli
      infection. We found in this study that Vdelta1-/- mice exhibited impaired
      accumulation of peritoneal macrophages but not neutrophils and delayed bacterial
      clearance after i.p. inoculation with E. coli. Peritoneal gammadelta T cells from
      E. coli-infected wild-type mice produced CCL3/MIP-1alpha and CCL5/RANTES in
      response to gammadelta TCR triggering in vitro, whereas such production was not
      evident in gammadelta T cells from E. coli-infected Vdelta1-/- mice.
      Neutralization of CCL3/MIP-1alpha by a specific mAb in vivo significantly
      inhibited the accumulation of macrophages in the peritoneal cavity after E. coli
      infection, resulting in exacerbated bacterial growth in the peritoneal cavity.
      These results suggest that Vdelta1+ gammadelta T cells bridge a gap between
      neutrophils and macrophages in innate immunity during E. coli infection mediated
      by production of CC chemokines, enhancing macrophage trafficking to the site of
      infection.

PMID- 15470061
TI  - Protease-activated receptor signaling increases epithelial antimicrobial peptide
      expression.
AB  - Epithelial tissues provide both a physical barrier and an antimicrobial barrier.
      Antimicrobial peptides of the human beta-defensin (hBD) family are part of the
      innate immune responses that play a role in mucosal defense. hBDs are made in
      epithelia including oral epithelium where the bacterial load is particularly
      great. hBD-2 and hBD-3 are up-regulated in response to bacterial stimuli.
      Previous studies show that hBD-2 expression in human gingival epithelial cells
      (GEC) is stimulated by both nonpathogenic and pathogenic bacteria, including
      Porphyromonas gingivalis, a Gram-negative pathogen associated with periodontitis.
      Present evidence suggests that hBD-2 expression in GEC uses several signaling
      pathways, including an NF-kappaB-mediated pathway but without apparent LPS-TLR4
      signaling. Protease-activated receptors (PAR) are G-protein-coupled receptors
      that mediate cellular responses to extracellular proteinases. P. gingivalis
      secretes multiple proteases that contribute to its virulence mechanisms. To
      determine whether PAR signaling is used in hBD-2 induction, GEC were stimulated
      with wild-type P. gingivalis or mutants lacking one or more proteases. hBD-2 mRNA
      expression was reduced in GEC stimulated with single protease mutants (11-67%
      compared with wild type), strongly reduced in double mutants (0.1-16%), and
      restored to wild-type levels (93%) in mutant with restored protease activity.
      Stimulation by wild type was partially blocked by inhibitors of phospholipase C,
      a main signaling pathway for PARs. Expression of hBD-3 was unaffected. Peptide
      agonist of PAR-2, but not PAR-1 activator, also induced hBD-2 in GEC. Thus, P.
      gingivalis proteases are directly involved in regulation of hBD-2 in cultured
      GEC, and this induction partially uses the PAR-2 receptor and signaling pathway.

PMID- 15470062
TI  - Impaired immunity to intestinal bacterial infection in stromelysin-1 (matrix
      metalloproteinase-3)-deficient mice.
AB  - Infection of mice with the intestinal bacterial pathogen Citrobacter rodentium
      results in colonic mucosal hyperplasia and a local Th1 inflammatory response
      similar to that seen in mouse models of inflammatory bowel disease. Matrix
      metalloproteinases (MMPs) have been shown to mediate matrix remodeling and cell
      migration during tissue injury and repair in the intestine. We have previously
      shown enhanced pathology in infected TNFRp55-/-, IL-12p40-/-, and IFN-gamma-/-
      mice, and here we show that this is associated with an increase in stromelysin-1
      (MMP3) transcripts in colonic tissues. We have therefore investigated the role of
      MMP3 in colonic mucosal hyperplasia and the local Th1 responses using MMP3-/-
      mice. In MMP3-/- mice, similar mucosal thickening was observed after infection as
      in wild-type (WT) mice. Colonic tissues from MMP3-/- mice showed a compensatory
      increase in the expression of other MMP transcripts, such as MMP7 and MMP12.
      However, MMP3-/- mice showed delayed clearance of bacteria and delayed appearance
      of CD4+ T lymphocytes into intestinal lamina propria. CSFE-labeled mesenteric
      lymph node CD4+ T lymphocytes from infected WT mice migrated in fewer numbers
      into the mesenteric lymph nodes and colon of MMP3-/- mice than into those of WT
      mice. These studies show that mucosal remodeling can occur in the absence of
      MMP3, but that MMP3 plays a role in the migration of CD4+ T lymphocytes to the
      intestinal mucosa.

PMID- 15470063
TI  - Endogenous IL-15 sustains recruitment of IL-2Rbeta and common gamma and IL-2
      mediated chemokine production in normal and inflamed human gingival fibroblasts.
AB  - We recently reported that anti-IL-15 neutralizing mAb has been shown to inhibit
      production of MCP-1 in response to IL-2 from normal human gingival fibroblasts
      (HGF), the major constituent of gingival tissue. In the present study, we
      examined the expression of IL-2R and IL-15R subunits in HGF from normal and
      inflamed regions and the role of endogenous IL-15 in IL-2-mediated signaling.
      Normal HGF expressed IL-2Rbeta and common gamma-chain (gammac) but not IL-2Ralpha
      or IL-15Ralpha, whereas inflamed HGF expressed IL-2Ralpha, IL-15Ralpha, IL
      2Rbeta, and gammac, as assessed by RT-PCR and flow cytometry. Exogenous IL-2 and
      IL-15 induced production of MCP-1 but not IL-8 in normal HGF, and induced the
      production of both chemokines in inflamed HGF. Both HGF constitutively
      transcribed the 48 aa-IL-15 isoform, and the isoform was not actively secreted
      but rather existed as a membrane-bound form. Pretreatment with anti-IL-15
      neutralizing mAb for 24 h completely inhibited the production of MCP-1 induced by
      IL-2 and IL-15 and IL-2-induced phosphorylation of Jak 1 and 3 in HGF. The
      pretreatment and RNA interference targeted to IL-15 mRNA resulted in total
      inhibition of the IL-2Rbeta and gammac expression at mRNA and protein levels.
      Furthermore, excess amounts of IL-2 restored the inhibitory effect of anti-IL-15,
      inhibition of NF-kappaB abrogated the expression of IL-2Rbeta and gammac, and IL
      2-induced-nuclear translocation of NF-kappaB was completely inhibited by the RNA
      interference in HGF. These results suggest that endogenous membrane-bound IL-15
      sustains recruitment of IL-2Rbeta and gammac through activation of NF-kappaB in
      HGF.

PMID- 15470064
TI  - Transendothelial migration of human basophils.
AB  - During allergic reactions, basophils migrate from the blood compartment to
      inflammatory sites, where they act as effector cells in concert with eosinophils.
      Because transendothelial migration (TEM) represents an essential step for
      extravasation of cells, for the first time we have studied basophil TEM using
      HUVEC. Treatment of HUVEC with IL-1beta significantly enhanced basophil TEM,
      which was further potentiated by the presence of a CCR3-specific ligand,
      eotaxin/CCL11. In addition to CCR3 ligands, MCP-1/CCL2 was also active on
      basophil TEM. Although stromal cell-derived factor-1/CXCL12, a CXCR4 ligand,
      failed to induce TEM in freshly isolated basophils, it caused strong TEM in 24-h
      cultured cells. IL-3 enhanced basophil TEM by increasing the chemokinetic
      response. Spontaneous TEM across activated HUVEC was inhibited by treatment of
      cells with anti-CD18 mAb, but not with anti-CD29 mAb, and also by treatment of
      HUVEC with anti-ICAM-1 mAb. Anti-VCAM-1 mAb alone failed to inhibit TEM, but
      showed an additive inhibitory effect in combination with anti-ICAM-1 mAb. In
      contrast, eotaxin- and IL-3-mediated TEM was significantly inhibited by anti-CD29
      mAb as well as anti-CD18 mAb. These results indicate that beta2 integrins play
      the primary role in basophil TEM, but beta1 integrins are also involved,
      especially in TEM of cytokine/chemokine-stimulated basophils. In conclusion, the
      regulatory profile of basophil TEM is very similar to that reported for
      eosinophils. Our results thus support the previous argument for a close
      relationship between basophils and eosinophils and suggest that the in vivo
      kinetics of these two cell types are similar.

PMID- 15470065
TI  - The 15-deoxy-delta12,14-prostaglandin J2 inhibits the inflammatory response in
      primary rat astrocytes via down-regulating multiple steps in phosphatidylinositol
      3-kinase-Akt-NF-kappaB-p300 pathway independent of peroxisome proliferator
      activated receptor gamma.
AB  - Ligands for peroxisome proliferator-activated receptor gamma (PPARgamma), such as
      15-deoxy-12,14-PGJ2 (15d-PGJ2), have been proposed as a new class of anti
      inflammatory compounds because 15d-PGJ2 was able to inhibit the induction of
      inflammatory response genes such as inducible NO synthase (iNOS) and TNF (TNF
      alpha) in a PPAR-dependent manner in various cell types. In primary astrocytes,
      the anti-inflammatory effects (inhibition of TNF-alpha, IL-1beta, IL-6, and iNOS
      gene expression) of 15d-PGJ2 are observed to be independent of PPARgamma.
      Overexpression (wild-type and dominant-negative forms) of PPARgamma and its
      antagonist (GW9662) did not alter the 15d-PGJ2-induced inhibition of LPS/IFN
      gamma-mediated iNOS and NF-kappaB activation. The 15d-PGJ2 inhibited the
      inflammatory response by inhibiting IkappaB kinase activity, which leads to the
      inhibition of degradation of IkappaB and nuclear translocation of p65, thereby
      regulating the NF-kappaB pathway. Moreover, 15d-PGJ2 also inhibited the LPS/IFN
      gamma-induced PI3K-Akt pathway. The 15d-PGJ2 inhibited the recruitment of p300 by
      NF-kappaB (p65) and down-regulated the p300-mediated induction of iNOS and NF
      kappaB luciferase reporter activity. Coexpression of constitutive active Akt and
      PI3K (p110) reversed the 15d-PGJ2-mediated inhibition of p300-induced iNOS and NF
      kappaB luciferase activity. This study demonstrates that 15d-PGJ2 suppresses
      inflammatory response by inhibiting NF-kappaB signaling at multiple steps as well
      as by inhibiting the PI3K/Akt pathway independent of PPARgamma in primary
      astrocytes.

PMID- 15470066
TI  - Key metalloproteinases are expressed by specific cell types in experimental
      autoimmune encephalomyelitis.
AB  - Metalloproteinases (MPs) include matrix metalloproteinases (MMPs) and
      metalloproteinase-disintegrins (ADAMs). Their physiological inhibitors are tissue
      inhibitor of metalloproteinases (TIMPs). MPs are thought to be mediators of
      cellular infiltration in the pathogenesis of multiple sclerosis and its animal
      model, experimental autoimmune encephalomyelitis (EAE). We used real-time RT-PCR
      to profile the expression of all 22 known mouse MMPs, seven ADAMs, and all four
      known TIMPs in spinal cord from SJL/J mice and mice with adoptively transferred
      myelin basic protein (MBP)-specific EAE. A significant and >3-fold alteration in
      expression was observed for MMP-8, MMP-10, MMP-12, ADAM-12, and TIMP-1, which
      were up-regulated, and for MMP-15, which was down-regulated. Expression levels
      correlated with disease course, with all but ADAM-12 returning toward control
      levels in remission. To examine potential cellular sources of these strongly
      affected proteins in the inflamed CNS, we isolated macrophages, granulocytes,
      microglia, and T cells by cell sorting from the CNS of mice with EAE and analyzed
      their expression by real-time RT-PCR. This identified macrophages as a major
      source of MMP-12 and TIMP-1. Granulocytes were a major source of MMP-8. ADAM-12
      was expressed primarily by T cells. Cellular localization of MMP-10, TIMP-1, and
      ADAM-12 in perivascular infiltrates was confirmed by immunostaining or in situ
      hybridization. Microglia from control mice expressed strong signal for MMP-15.
      Strikingly, the expression of MMP-15 by microglia was significantly down
      regulated in EAE, which was confirmed by immunostaining. Our study identifies the
      cellular sources of key MPs in CNS inflammation.

PMID- 15470067
TI  - Bradykinin B2 receptor mediates NF-kappaB activation and cyclooxygenase-2
      expression via the Ras/Raf-1/ERK pathway in human airway epithelial cells.
AB  - In this study, we investigated the signaling pathways involved in bradykinin (BK)
      induced NF-kappaB activation and cyclooxygenase-2 (COX-2) expression in human
      airway epithelial cells (A549). BK caused concentration- and time-dependent
      increase in COX-2 expression, which was attenuated by a selective B2 BK receptor
      antagonist (HOE140), a Ras inhibitor (manumycin A), a Raf-1 inhibitor (GW 5074),
      a MEK inhibitor (PD 098059), an NF-kappaB inhibitor (pyrrolidine dithiocarbate),
      and an IkappaB protease inhibitor (L-1-tosylamido-2-phenylethyl chloromethyl
      ketone). The B1 BK receptor antagonist (Lys-(Leu8)des-Arg9-BK) had no effect on
      COX-2 induction by BK. BK-induced increase in COX-2-luciferase activity was
      inhibited by cells transfected with the kappaB site deletion of COX-2 construct.
      BK-induced Ras activation was inhibited by manumycin A. Raf-1 phosphorylation at
      Ser338 by BK was inhibited by manumycin A and GW 5074. BK-induced ERK activation
      was inhibited by HOE140, manumycin A, GW 5074, and PD 098059. Stimulation of
      cells with BK activated IkappaB kinase alphabeta (IKKalphabeta), IkappaBalpha
      phosphorylation, IkappaBalpha degradation, p65 and p50 translocation from the
      cytosol to the nucleus, the formation of an NF-kappaB-specific DNA-protein
      complex, and kappaB-luciferase activity. BK-mediated increase in IKKalphabeta
      activity and formation of the NF-kappaB-specific DNA-protein complex were
      inhibited by HOE140, a Ras dominant-negative mutant (RasN17), manumycin A, GW
      5074, and PD 098059. Our results demonstrated for the first time that BK, acting
      through B2 BK receptor, induces activation of the Ras/Raf-1/ERK pathway, which in
      turn initiates IKKalphabeta and NF-kappaB activation, and ultimately induces COX
      2 expression in human airway epithelial cell line (A549).

PMID- 15470068
TI  - Bacterial lipoprotein delays apoptosis in human neutrophils through inhibition of
      caspase-3 activity: regulatory roles for CD14 and TLR-2.
AB  - The human sepsis syndrome resulting from bacterial infection continues to account
      for a significant proportion of hospital mortality. Neutralizing strategies aimed
      at individual bacterial wall products (such as LPS) have enjoyed limited success
      in this arena. Bacterial lipoprotein (BLP) is a major constituent of the wall of
      diverse bacterial forms and profoundly influences cellular function in vivo and
      in vitro, and has been implicated in the etiology of human sepsis. Delayed
      polymorphonuclear cell (PMN) apoptosis is a characteristic feature of human
      sepsis arising from Gram-negative or Gram-positive bacterial infection. Bacterial
      wall product ligation and subsequent receptor-mediated events upstream of caspase
      inhibition in neutrophils remain incompletely understood. BLP has been shown to
      exert its cellular effects primarily through TLR-2, and it is now widely accepted
      that lateral associations with the TLRs represent the means by which CD14
      communicates intracellular messages. In this study, we demonstrate that BLP
      inhibits neutrophil mitochondrial membrane depolarization with a subsequent
      reduction in caspase-3 processing, ultimately leading to a significant delay in
      PMN apoptosis. Pretreatment of PMNs with an anti-TLR-2 mAb or anti-CD14 mAb
      prevented BLP from delaying PMN apoptosis to such a marked degree. Combination
      blockade using both mAbs completely prevented the effects of BLP (in 1 and 10
      ng/ml concentrations) on PMN apoptosis. At higher concentrations of BLP, the
      antiapoptotic effects were observed, but were not as pronounced. Our findings
      therefore provide the first evidence of a crucial role for both CD14 and TLR-2 in
      delayed PMN apoptosis arising from bacterial infection.

PMID- 15470069
TI  - A mouse herpesvirus induces relapse of experimental autoimmune arthritis by
      infection of the inflammatory target tissue.
AB  - It is not known what is required for successive relapses in autoimmune diseases
      or evolution to a progressive chronic disease. Autoimmune arthritis caused by
      passive transfer of autoantibodies against glucose 6-phosphate isomerase is
      transient and therefore lends itself well to test for what might extend the
      disease. Herpesviruses have long been suspected of contributing to human
      autoimmune disease. We infected mice with a murine gamma-herpesvirus (MHV-68). In
      immunodeficient mice, transient arthritis was followed by a relapse. This was due
      to lytic viral infection of synovial tissues demonstrated by PCR,
      immunohistochemistry, and electron microscopy. Latent infection could be
      reactivated in the synovium of normal mice when treated with Cytoxan and this was
      associated with increased clinical arthritis. We conclude that herpesviruses may
      play an ancillary pathogenic role in autoimmune arthritis by infection of the
      inflammatory target tissue.

PMID- 15470070
TI  - T cell proliferation by direct cross-talk between OX40 ligand on human mast cells
      and OX40 on human T cells: comparison of gene expression profiles between human
      tonsillar and lung-cultured mast cells.
AB  - Mast cells (MCs) are the primary effector cells in allergic reactions and have
      also been found to activate T cells and to reside in close physical proximity to
      T cells. However, the molecular mechanisms involved in the MC-T cell interaction
      remain unclear. We hypothesized that human tonsillar MCs, which locate in the
      interfollicular areas, might interact with T cells. Thus, we first established a
      culture system of human tonsillar MCs and then compared gene expression profiles
      of tonsillar MCs with that of lung MCs before and after aggregation of
      FcepsilonRI by using high-density oligonucleotide probe arrays. Here we show that
      resting tonsillar MCs, when compared with lung MCs, revealed significantly higher
      expression levels for CC chemokines (CCL3 and 4), which recruit T cells, and for
      TNFR superfamilies (OX40 ligand and 4-1BB ligand), which induce proliferation of
      T cells. After aggregation of FcepsilonRI, not only tonsillar MCs but also lung
      MCs up-regulated the expression of these molecules. We confirmed that T cell
      proliferation is induced in direct cross-talk by the MC surface molecule OX40
      ligand. These results suggest that human MCs may play important roles in adaptive
      immunity through the T cell responses.

PMID- 15470071
TI  - Allergy vaccine engineering: epitope modulation of recombinant Bet v 1 reduces
      IgE binding but retains protein folding pattern for induction of protective
      blocking-antibody responses.
AB  - Human type 1 immediate allergic response symptoms are caused by mediator release
      from basophils and mast cells. This event is triggered by allergens aggregating
      preformed IgE Abs bound to the high-affinity receptor (FcepsilonRI) on these
      cells. Thus, the allergen/IgE interaction is crucial for the cascade leading to
      the allergic and anaphylactic response. Two genetically engineered forms of the
      white birch pollen major allergen Bet v 1 with point mutations directed at
      molecular surfaces have been characterized. Four and nine point mutations led to
      a significant reduction of the binding to human serum IgE, suggesting a mutation
      induced distortion of IgE-binding B cell epitopes. In addition, the mutated
      allergens showed a decrease in anaphylactic potential, because histamine release
      from human basophils was significantly reduced. Retained alpha-carbon backbone
      folding pattern of the mutated allergens was indicated by x-ray diffraction
      analysis and circular dichroism spectroscopy. The rBet v 1 mutants were able to
      induce proliferation of T cell lines derived from birch pollen allergic patients.
      The stimulation indices were similar to the indices of nonmutated rBet v 1 and
      natural Bet v 1 purified from birch pollen. The ability of anti-rBet v 1 mutant
      specific mouse IgG serum to block binding of human serum IgE to rBet v 1
      demonstrates that the engineered rBet v 1 mutants are able to induce Abs reactive
      with nonmodified Bet v 1. rBet v 1 mutants may constitute vaccine candidates with
      improved efficacy/safety profiles for safer allergy vaccination.

PMID- 15470072
TI  - Role of L-selectin in the vascular homing of peripheral blood-derived endothelial
      progenitor cells.
AB  - Ex vivo expanded endothelial progenitor cells (EPCs) represent a new potential
      approach for the revascularization of ischemic sites. However, local accumulation
      of infused EPCs in these sites is poor, and the mechanisms responsible for their
      homing are largely unknown. We observed the expression of L-selectin, an adhesion
      receptor that regulates lymphocyte homing and leukocyte rolling and migration, on
      ex vivo expanded blood-derived human EPCs. When EPCs were subcloned in SV40-T
      large Ag-transfected isolates, the copresence of L-selectin and endothelial
      lineage markers was confirmed. We therefore demonstrated that the expression of L
      selectin by EPCs was functional because it mediates interaction with a murine
      endothelial cell line (H.end) expressing L-selectin ligands by way of
      transfection with alpha(1,3/4)-fucosyltransferase. Indeed, adhesion of EPCs after
      incubation at 4 degrees C on a rotating platform was enhanced on alpha(1,3/4)
      fucosyltransferase-transfected H.end cells compared with control vector
      transfected cells, and treatment with anti-L-selectin Abs prevented this event.
      We then studied the role of L-selectin in EPC homing in vivo. H.end cells were
      implanted s.c. in SCID mice to form endothelioma tumors, and EPCs were
      subsequently i.v. injected. L-selectin+ EPCs localized into alpha(1,3/4)
      fucosyltransferase-transfected endothelial tumors to a greater extent than in
      control tumors, and they were able to directly contribute to tumor
      vascularization by forming L-selectin+ EPC-containing vessels. In conclusion, our
      results showed that a mechanism typical of leukocyte adhesion is involved in the
      vascular homing of EPCs within sites of selectin ligand expression. This
      observation may provide knowledge about the substrate to design strategies to
      improve EPC localization in damaged tissues.

PMID- 15470073
TI  - IgE-mediated mast cell activation induces Langerhans cell migration in vivo.
AB  - Langerhans cells and mast cells are both resident in large numbers in the skin
      and act as sentinel cells in host defense. The ability of mast cells to induce
      Langerhans cell migration from the skin to the draining lymph node in vivo was
      examined. Genetically mast cell-deficient (W/Wv) mice and control mice were
      sensitized with IgE Ab in the ear pinna. Seven to 14 days later, mice were
      challenged with Ag i.v. After a further 18-24 h, epidermal sheets and draining
      auricular lymph nodes were examined using Langerin/CD207 immunostaining. In mast
      cell-containing mice, a significant decrease in the number of Langerhans cells
      was observed at epidermal sites of mast cell activation. A significant increase
      in total cellularity and accumulation of Langerin-positive dendritic cells was
      observed in the auricular lymph nodes, draining the sites of IgE-mediated mast
      cell activation. These changes were not observed in W/Wv mice, but were restored
      by local mast cell reconstitution. Treatment of mast cell-containing mice with
      the H2 receptor antagonist cimetidine significantly inhibited the observed IgE/Ag
      induced changes in Langerhans cell location. In contrast, Langerhans cell
      migration in response to LPS challenge was not mast cell dependent. These data
      directly demonstrate the ability of mast cells to induce dendritic cell migration
      to lymph nodes following IgE-mediated activation in vivo by a histamine-dependent
      mechanism.

PMID- 15470074
TI  - Expansion of bone marrow IFN-alpha-producing dendritic cells in New Zealand Black
      (NZB) mice: high level expression of TLR9 and secretion of IFN-alpha in NZB bone
      marrow.
AB  - Patients with systemic lupus erythematosus have elevated IFN-alpha production.
      Furthermore, sera IFN-alpha levels correlate with disease activity. We have
      focused our attention on whether this phenotype is also seen in the New Zealand
      Black (NZB) mice and simultaneously addressed the underlying mechanisms.
      Specifically, we analyzed: 1) levels of sera IFN-alpha after type A CpG ODN 2216
      injection in autoimmunity-prone NZB and control mice, and 2) levels of IFN-alpha
      synthesized by IFN-alpha-producing dendritic cells (IPDCs) using highly enriched
      populations of CD11c+B220+ IPDCs derived from NZB and control mice; IPDCs are
      divided into two subpopulations (CD4+CD11c+B220+ and CD4-CD11c+B220+). Our data
      demonstrate that NZB mice produced higher levels of sera IFN-alpha after type A
      CpG ODN 2216 injection when compared with control mice (p < 0.01). In addition,
      the cell numbers, frequency, and TLR9 mRNA levels of CD4+ and CD4- IPDC were
      markedly increased in the bone marrow (BM) of NZB mice. Upon in vitro stimulation
      with TLR9 ligand-CpG ODN 2216, higher levels of IFN-alpha were synthesized by
      IPDCs from the BM of NZB. The major contributor of IFN-alpha was the CD4
      CD11c+B220+ IPDC subpopulation. Furthermore, NZB BM IPDCs manifest impaired
      expression of homing chemokine CCR7 and CD62L, and IL-12 production. These data
      on the functional characteristics of the IPDC lineages explain in part the
      mechanism of hyper-IFN-alpha production and help clarify the mechanism for the
      expansion of NZB BM IPDCs.

PMID- 15470075
TI  - Inhibition of T cell apoptosis in the aqueous humor of patients with uveitis by
      IL-6/soluble IL-6 receptor trans-signaling.
AB  - A fundamental mechanism of immune privilege in the eye is the induction of T
      lymphocyte apoptosis. Intraocular inflammation in uveitis implies compromise of
      immune privilege. This study sought to determine whether apoptosis of T cells is
      actively inhibited in patients with uveitis and by what pathways this may occur.
      Apoptotic lymphocytes were found to be absent from aqueous humor (AqH) of
      virtually all patients with recent-onset uveitis. However, T cells removed from
      the eye were highly susceptible to both spontaneous and Fas ligand-induced
      apoptosis in vitro. AqH from patients with uveitis had no modulatory effect on
      Fas ligand-induced apoptosis, but strongly suppressed survival factor deprivation
      induced apoptosis. In contrast, noninflammatory AqH from patients undergoing
      cataract surgery had no modulatory effects on apoptosis at all. These data
      suggest that triggering of the Fas pathway is diminished in uveitis, and also
      that homeostatic resolution through survival factor deprivation-induced apoptosis
      is inhibited by factors present in AqH. The most widely recognized pathways,
      common gamma-chain cytokines and type I IFNs, did not contribute to AqH-mediated
      T cell survival. High levels of both IL-6 and soluble IL-6R were found in AqH. IL
      6 alone did not induce T cell survival, because IL-6R expression on T cells in
      AqH was too low to facilitate signaling. However, combinations of IL-6 and
      soluble IL-6R were highly effective inhibitors of T cell apoptosis, suggesting
      that the trans-signaling pathway is likely to be a key mediator of T cell
      apoptosis inhibition mediated by uveitis AqH.

PMID- 15470076
TI  - Gamma-aminobutyric acid inhibits T cell autoimmunity and the development of
      inflammatory responses in a mouse type 1 diabetes model.
AB  - Gamma-aminobutyric acid (GABA) is both a major inhibitory neurotransmitter in the
      CNS and a product of beta cells of the peripheral islets. Our previous studies,
      and those of others, have shown that T cells express functional GABAA receptors.
      However, their subunit composition and physiological relevance are unknown. In
      this study, we show that a subset of GABAA receptor subunits are expressed by
      CD4+ T cells, including the delta subunit that confers high affinity for GABA and
      sensitivity to alcohol. GABA at relatively low concentrations down-regulated
      effector T cell responses to beta cell Ags ex vivo, and administration of GABA
      retarded the adoptive transfer of type 1 diabetes (T1D) in NOD/scid mice.
      Furthermore, treatment with low dose of GABA (600 microg daily) dramatically
      inhibited the development of proinflammatory T cell responses and disease
      progression in T1D-prone NOD mice that already had established autoimmunity.
      Finally, GABA inhibited TCR-mediated T cell cycle progression in vitro, which may
      underlie GABA's therapeutic effects. The immunoinhibitory effects of GABA on T
      cells may contribute to the long prodomal period preceding the development of
      T1D, the immunological privilege of the CNS, and the regulatory effects of
      alcohol on immune responses. Potentially, pharmacological modulation of GABAA
      receptors on T cells may provide a new class of therapies for human T1D as well
      as other inflammatory diseases.

PMID- 15470077
TI  - Increased natural killer cell activity in viremic HIV-1 infection.
AB  - NK cells are a subset of granular lymphocytes that are critical in the innate
      immune response to infection. These cells are capable of killing infected cells
      and secreting integral cytokines and chemokines. The role that this subset of
      cytolytic cells plays in HIV infection is not well understood. In this study, we
      dissected the function of NK cells in viremic and aviremic HIV-1-infected
      subjects, as well as HIV-1-negative control individuals. Despite reduced NK cell
      numbers in subjects with ongoing viral replication, these cells were
      significantly more active in secreting both IFN-gamma and TNF-alpha than NK cells
      from aviremic subjects or HIV-1-negative controls. In addition, NK cells in
      subjects with detectable viral loads expressed significantly higher levels of
      CD107a, a marker of lysosomal granule exocytosis. The expression of CD107a
      correlated with NK cell-mediated cytokine secretion and cytolytic activity as
      well as with the level of viral replication, suggesting that CD107a represents a
      good marker for the functional activity of NK cells. Finally, killer Ig-related
      receptor+ NK cells were stable or elevated in viremic subjects, while the numbers
      of CD3-/CD56+/CD94+ and CD3-/CD56+/CD161+ NK cells were reduced. Taken together,
      these data demonstrate that viremic HIV-1 infection is associated with a
      reduction in NK cell numbers and a perturbation of NK cell subsets, but increased
      overall NK cell activity.

PMID- 15470078
TI  - Blockade of IL-18 receptor signaling delays the onset of autoimmune disease in
      MRL-Faslpr mice.
AB  - Autoimmune disease in Fas-deficient MRL-Faslpr mice is dependent on infiltrating
      autoreactive leukocytes and autoantibodies, and IFN-gamma plays an important role
      in the pathogenesis. As IL-18 is capable of inducing IFN-gamma production in T
      cells, we hypothesized that signaling through IL-18R is involved in the
      pathogenesis. To investigate the impact of IL-18 in this autoimmune disease, we
      generated an MRL-Faslpr strain deficient in IL-18Ralpha. Compared with the wild
      type strain, IL-18Ralpha-deficient MRL-Faslpr mice survived longer and showed a
      significant reduction in renal pathology, including glomerular IgG deposits,
      proteinuria, and serum anti-DNA Abs. Intrarenal transcripts encoding IFN-gamma,
      TNF-alpha, IL-12, and IL-10, which have been linked to nephritis, were all
      markedly reduced. Skin lesions, lymphadenopathy, and lung pathology
      characteristic of the MRL-Faslpr mouse disease were diminished in IL-18Ralpha
      deficient MRL-Faslpr mice. Thus, we conclude that IL-18Ralpha signaling is
      critical to the pathogenesis of autoimmune disease in MRL-Faslpr mice.

PMID- 15470079
TI  - Subunit composition of nicotinic receptors in monkey striatum: effect of
      treatments with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or L-DOPA.
AB  - Nicotinic acetylcholine receptors (nAChRs) represent an important modulator of
      striatal function both under normal conditions and in pathological states such as
      Parkinson's disease. Because different nAChR subtypes may have unique functions,
      immunoprecipitation and ligand binding studies were done to identify their
      subunit composition. As in the rodent, alpha2, alpha4, alpha6, beta2, and beta3
      nAChR subunit immunoreactivity was identified in monkey striatum. However,
      distinct from the rodent, the present results also revealed the novel presence of
      alpha3 nAChR subunit-immunoreactivity in this same region, but not that for
      alpha5 and beta4. Relatively high levels of alpha2 and alpha3 subunits were also
      identified in monkey cortex, in addition to alpha4 and beta2. Experiments were
      next done to determine whether striatal subunit expression was changed with
      nigrostriatal damage. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment
      decreased alpha6 and beta3 subunit immunoreactivity by approximately 80% in
      parallel with the dopamine transporter, suggesting that they are predominantly
      expressed on nigrostriatal dopaminergic projections. In contrast, alpha3, alpha4,
      and beta2 subunit immunoreactivity was decreased approximately 50%, whereas
      alpha2 was not changed. These data, together with those from dual
      immunoprecipitation and radioligand binding studies ([(3)H]cytisine, (125)I-alpha
      bungarotoxin, and (125)I-alpha-conotoxin MII) suggest the following: that
      alpha6beta2beta3, alpha6alpha4beta2beta3, and alpha3beta2* nAChR subtypes are
      present on dopaminergic terminals and that the alpha4beta2 subtype is localized
      on both dopaminergic and nondopaminergic neurons, whereas alpha2beta2* and alpha7
      receptors are localized on nondopaminergic cells in monkey striatum. Overall,
      these results suggest that drugs targeting non-alpha7 nicotinic receptors may be
      useful in the treatment of disorders characterized by nigrostriatal dopaminergic
      damage, such as Parkinson's disease.

PMID- 15470080
TI  - Histidine residues 912 and 913 in protein associated with Myc are necessary for
      the inhibition of adenylyl cyclase activity.
AB  - We reported previously that protein associated with Myc (PAM) interacts with the
      C2 domain of type V adenylyl cyclase (ACV-C2) and that purified PAM is a potent
      inhibitor of Galphas-stimulated ACV activity (J Biol Chem 276:47583-47589, 2001).
      The present study was conducted to identify the region in PAM that inhibits ACV
      activity and to determine whether its binding with the ACV-C2 is necessary and
      sufficient to inhibit the enzyme. Coexpression of ACV and full-length PAM or its
      N-terminal third (PAM-N) in COS-7 cells inhibited isoproterenol-stimulated cAMP
      accumulation. Deletion of the RCC1 homology domains in PAM-N abolished its
      ability to inhibit isoproterenol-stimulated cAMP formation in cells. Purified GST
      fusion protein of the second RCC1 homology domain (RHD2) of PAM was sufficient to
      bind with ACV-C2 and inhibit Galphas-stimulated ACV activity. In addition,
      deletion of 11 amino acids in GST-RHD2 obliterated its ability to bind with and
      inhibit ACV. The C terminus of the RHD2 domain bound with ACV-C2 without
      inhibiting enzyme activity. Furthermore, substitution of His912 and His913 with
      alanine in the GST-RHD2 obliterated its ability to inhibit ACV without altering
      binding to ACV-C2. Likewise, H912/913A mutants of both PAM-N and full-length PAM
      did not inhibit cAMP formation in cells. Thus, the RHD2 domain of PAM is
      sufficient to inhibit Galphas-stimulated ACV activity and the binding of RHD2 to
      ACV-C2 is necessary but not sufficient for this inhibition. Moreover, His912 and
      His913 in PAM are critical for inhibiting ACV.

PMID- 15470081
TI  - Hepatic expression of the UGT1A9 gene is governed by hepatocyte nuclear factor
      4alpha.
AB  - UDP-glucuronosyltransferase (UGT) enzymes catalyze the glucuronidation reaction,
      which is a major pathway in the catabolism and elimination of numerous endo- and
      xenobiotics. Among the UGT enzyme family members, the UGT1A7, UGT1A8, UGT1A9, and
      UGT1A10 isoforms are issued from a single gene through differential splicing.
      However, these enzymes display distinct tissue-specific expression patterns.
      Indeed, UGT1A7, UGT1A8, and UGT1A10 are exclusively expressed in extrahepatic
      tissues, whereas UGT1A9 transcripts are found at high concentrations in liver. In
      the present study, we report that the liver-enriched hepatocyte nuclear factor 4
      (HNF4)-alpha controls the hepatic expression of the UGT1A9 enzyme. Liver-specific
      disruption of the HNF4alpha gene in mice drastically decreases liver UGT1A9 mRNA
      levels. Furthermore, an HNF4alpha response element (HNF4alpha RE) was identified
      in the promoter of human UGT1A9 at position -372 to -360 base pairs by transient
      transfection, electrophoretic mobility shift assays, and chromatin
      immunoprecipitation experiments. It is interesting that this response element is
      absent in the proximal UGT1A7, UGT1A8, and UGT1A10 gene promoters. In conclusion,
      the present study identifies HNF4alpha as a major factor for the control of
      UGT1A9 hepatic expression and suggests that the absence of UGT1A7, UGT1A8, and
      UGT1A10 expression in the liver is caused by, at least in part, a few base pair
      changes in their promoter sequences in the region corresponding to the HNF4alpha
      RE of the UGT1A9 gene.

PMID- 15470082
TI  - Proteochemometric mapping of the interaction of organic compounds with
      melanocortin receptor subtypes.
AB  - Proteochemometrics was applied in the analysis of the binding of organic
      compounds to wild-type and chimeric melanocortin receptors. Thirteen chimeric
      melanocortin receptors were designed based on statistical molecular design; each
      chimera contained parts from three of the MC(1,3-5) receptors. The binding
      affinities of 18 compounds were determined for these chimeric melanocortin
      receptors and the four wild-type melanocortin receptors. The data for 14 of these
      compounds were correlated to the physicochemical and structural descriptors of
      compounds, binary descriptors of receptor sequences, and cross-terms derived from
      ligand and receptor descriptors to obtain a proteochemometric model (correlation
      was performed using partial least-squares projections to latent structures; PLS).
      A well fitted mathematical model (R(2) = 0.92) with high predictive ability (Q(2)
      = 0.79) was obtained. In a further validation of the model, the predictive
      ability for ligands (Q(2)lig = 0.68) and receptors (Q(2)rec = 0.76) was
      estimated. The model was moreover validated by external prediction by using the
      data for the four additional compounds that had not at all been included in the
      proteochemometric model; the analysis yielded a Q(2)ext = 0.73. An interpretation
      of the results using PLS coefficients revealed the influence of particular
      properties of organic compounds on their affinity to melanocortin receptors.
      Three-dimensional models of melanocortin receptors were also created, and
      physicochemical properties of the amino acids inside the receptors' transmembrane
      cavity were correlated to the PLS modeling results. The importance of particular
      amino acids for selective binding of organic compounds was estimated and used to
      outline the ligand recognition site in the melanocortin receptors.

PMID- 15470083
TI  - Protein kinase C and epidermal growth factor stimulation of Raf1 potentiates
      adenylyl cyclase type 6 activation in intact cells.
AB  - Adenylyl cyclase type 6 (AC6) activity is inhibited by protein kinase C (PKC) in
      vitro; however, in intact cells, PKC activation does not inhibit the activity of
      transiently expressed AC6. To investigate the effects of PKC activation on AC6
      activity in intact cells, we constructed human embryonic kidney (HEK) 293 cells
      that stably express wild-type AC6 (AC6-WT) or an AC6 mutant lacking a PKC and
      cyclic AMP-dependent protein kinase (PKA) phosphorylation site, Ser674 (AC6
      S674A). In contrast to in vitro observations, we observed a PKC-mediated
      enhancement of forskolin- and isoproterenol-stimulated cyclic AMP accumulation in
      HEK-AC6 cells. Phorbol 12-myristate 13-acetate also potentiated cyclic AMP
      accumulation in cells expressing endogenous AC6, including Chinese hamster ovary
      cells and differentiated Cath.a differentiated cells. In HEK-AC6-S674A cells, the
      potentiation of AC6 stimulation was significantly greater than in cells
      expressing AC6-WT. The positive effect of PKC activation on AC6 activity seemed
      to involve Raf1 kinase because the Raf1 inhibitor 3-(3,5-dibromo-4
      hydroxybenzylidene-5-iodo-1,3-dihydro-indol-2-one (GW5074) inhibited the PKC
      potentiation of AC6 activity. Furthermore, the forskolin-stimulated activity of a
      recombinant AC6 in which the putative Raf1 regulatory sites have been eliminated
      was not potentiated by activation of PKC. The ability of Raf1 to regulate AC6 may
      involve a direct interaction because AC6 and a constitutively active Raf1
      construct were coimmunoprecipitated. In addition, we report that epidermal growth
      factor receptor activation also enhances AC6 signaling in a Raf1-dependent
      manner. These data suggest that Raf1 potentiates drug-stimulated cyclic AMP
      accumulation in cells expressing AC6 after activation of multiple signaling
      pathways.

PMID- 15470084
TI  - Comparison study between the mechanisms of allergic asthma amelioration by a
      cysteinyl-leukotriene type 1 receptor antagonist montelukast and
      methylprednisolone.
AB  - We investigated the effects of cysteinyl-leukotriene (cysLT) type 1 receptor
      antagonist montelukast (MK) and compared them with those of methylprednisolone
      (MP) in an allergic asthma model. Rats sensitized to ovalbumin (OVA) received
      repeated intratracheal exposure to OVA for up to 3 consecutive days. Pretreatment
      with MK or MP before OVA exposure inhibited late airway response (LAR) and
      reduced cellular infiltration into the bronchial submucosa after the triple OVA.
      The amount of N-acetyl-leukotriene E(4) in the bile was significantly reduced by
      pretreatment with MK or MP, suggesting that both drugs reduced the production of
      cysLTs in the lungs. In the in vitro study, when the fragments of lungs that had
      been repeatedly pretreated with MK or MP and exposed to OVA were removed and
      incubated with OVA, the coaddition of either drug significantly reduced cysLT
      production. In contrast, the cysLT production following the addition of OVA to
      the lung fragments that had not received in vivo pretreatment with either drug
      was inhibited by MK but not by MP. These results indicate that MK and MP inhibit
      LAR by suppressing the infiltration of inflammatory cells into the bronchial
      submucosa, thereby inhibiting the production of cysLTs in the lungs, and that MK
      but not MP may inhibit cysLT production directly. The different effects on cysLT
      production between the two drugs may provide a rationale for the use of
      combination therapy with cysLT(1) receptor antagonists and steroids for the
      treatment of asthma.

PMID- 15470085
TI  - Evaluation of tamsulosin and alfuzosin activity in the rat vas deferens:
      relevance to ejaculation delays.
AB  - The effect of two alpha-adrenergic receptor antagonists widely employed in the
      therapy of benign prostatic hyperplasia, tamsulosin [(-)-(R)-5-[2-[[2-(0
      ethoxyphenoxy) ethyl]amino]propyl]-2-methoxybenzenesulfonamide] and alfuzosin
      [(+/-)-N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl) methylamino]propyl]
      tetrahydro-2-furancarboxamide], was investigated in the rat vas deferens. Because
      several clinical studies have shown that tamsulosin causes ejaculatory disorders,
      this study also evaluated the possible mechanisms implicated in these disorders
      by comparing the effect of tamsulosin with that of alfuzosin. Tamsulosin
      competitively antagonized the contractions induced by noradrenaline in vitro in
      the epididymal portion of the vas deferens with a potency pA(2) value of 9.2 +/-
      0.8. In the prostatic portion, tamsulosin increased the amplitude of intermittent
      spikes induced by exogenous noradrenaline (100-1000 microM). In both portions of
      the vas deferens, alfuzosin behaved as an alpha-adrenergic antagonist blocking
      the contractions induced by exogenous noradrenaline without altering spikes. The
      administration of tamsulosin (3 microg/kg i.v.) significantly reduced the
      contractions evoked by electrical pulses in the epididymal portion, whereas it
      increased those produced in the prostatic portion. Intravenous tamsulosin
      antagonized the contraction produced by exogenous noradrenaline, whereas
      alfuzosin administration (10 microg/kg i.v.) did not change the electrically
      induced contractions in both portions of the rat vas deferens and did not
      antagonize the contractions produced by exogenous noradrenaline. The fact that
      tamsulosin unusually enhances noradrenaline-induced intermittent spike
      contractions and nerve stimulation-induced twitches in the prostatic portions
      might be linked to its greater propensity to cause sexual dysfunctions.

PMID- 15470086
TI  - Retinoic acid down-regulates aldehyde dehydrogenase and increases cytotoxicity of
      4-hydroperoxycyclophosphamide and acetaldehyde.
AB  - Multiple prior studies have identified aldehyde dehydrogenases (ALDH) that are
      capable of oxidizing retinal to retinoic acid. In this study, we test the
      hypothesis that the accumulation of intracellular retinoic acid may lead to the
      suppression of ALDH expression and thus increase cytotoxicity to 4
      hydroperoxycyclophosphamide (4-HC) in vitro. Mainly A549, but also other lung
      cancer cell lines, were used in our experiments, with the former having high
      levels of two ALDH isozymes expressed. Dose-response and time-course experiments
      were performed by incubating the cells with all-trans retinoic acid (ATRA) as
      well as other commercially available retinoids. The results show that incubation
      of A549 cells with any of the retinoids at pharmacologic doses for > or =48 h
      results in a significant decrease in ALDH-1A1 and ALDH-3A1 enzyme activity and
      protein levels but not the corresponding mRNAs. Such a decrease in ALDH activity
      was seen in all cell lines tested and results in a significant increase in
      toxicity of 4-HC and acetaldehyde, both of which are substrates for the enzymes.
      Prior incubation with ATRA also results in increased cytotoxicity, although to a
      lesser degree, of phenylketophosphamide and melphalan, neither of which is a
      substrate for ALDHs. These results suggest a post-translational mechanism through
      which retinoids decrease both ALDH expression, which results in increased
      cytotoxicity of 4-HC and acetaldehyde, although other previously described
      effects of these retinoids may contribute to the slight increase in cytotoxicity
      seen with other chemotherapy agents. These results may have clinical implications
      in regard to the use of retinoids in lung cancer prevention and treatment.

PMID- 15470087
TI  - Genome update: chromosome atlases.

PMID- 15470088
TI  - Congruence between strain morphology and the 16S rRNA gene sequence.

PMID- 15470090
TI  - Singular structures and operon organizations of essential two-component systems
      in species of Streptococcus.

PMID- 15470091
TI  - Fungal cell wall biogenesis: building a dynamic interface with the environment.

PMID- 15470092
TI  - Multiple sequence signals determine the distribution of
      glycosylphosphatidylinositol proteins between the plasma membrane and cell wall
      in Saccharomyces cerevisiae.
AB  - Glycosylphosphatidylinositol (GPI)-anchored cell wall proteins (GPI-CWPs) play an
      important role in the structure and function of the cell wall in Saccharomyces
      cerevisiae and other fungi. While the majority of characterized fungal GPI
      anchored proteins localize to the cell wall, a subset of GPI proteins are thought
      to reside at the plasma membrane and not to traffic significantly to the cell
      wall. The amino acids immediately upstream of the site of GPI anchor addition
      (the omega site) are the primary signal determining whether a GPI protein
      localizes to the cell wall or to the plasma membrane. Here, evidence was found
      that in addition to this omega-proximal signal, other sequences in the protein
      can impact the distribution of GPI proteins between cell wall and membrane. In
      particular, it was found that long regions rich in serine and threonine residues
      (a feature of many cell wall proteins) can override the omega-proximal signal and
      redirect a model GPI plasma membrane protein to the cell wall.

PMID- 15470093
TI  - Deficiencies in the essential Smp3 mannosyltransferase block
      glycosylphosphatidylinositol assembly and lead to defects in growth and cell wall
      biogenesis in Candida albicans.
AB  - Glycosylphosphatidylinositols (GPIs) are essential for viability in yeast and
      have key roles in cell wall construction. Assembly of Saccharomyces cerevisiae
      GPIs includes the addition of a fourth, side-branching mannose (Man) to the third
      Man of the core GPI glycan by the Smp3 mannosyltransferase. The SMP3 gene from
      the human pathogenic fungus Candida albicans has been cloned. CaSMP3 complements
      the inviable S. cerevisiae smp3 null mutant and, when expressed in an S.
      cerevisiae smp3/gpi13 double mutant, it permits in vivo conversion of the Man3
      GPI precursor that accumulates in that mutant to a Man4-GPI. One allele of CaSMP3
      was disrupted using the ura-blaster procedure, then the remaining allele was
      placed under the control of the glucose-repressible MAL2 promoter. Repression of
      CaSMP3 expression leads to accumulation of a GPI precursor glycolipid whose
      glycan headgroup contains three mannoses and bears a phosphodiester-linked
      substituent on its first Man. Under repressing conditions, cells exhibited
      morphological and cell wall defects and became inviable. CaSmp3p therefore adds a
      fourth, alpha1,2-linked Man to trimannosyl GPI precursors in C. albicans and is
      necessary for viability. Because addition of a fourth Man to GPIs is of less
      relative importance in mammals, Smp3p is a potential antifungal target.

PMID- 15470094
TI  - Systematic identification in silico of covalently bound cell wall proteins and
      analysis of protein-polysaccharide linkages of the human pathogen Candida
      glabrata.
AB  - Candida glabrata is an important cause of systemic candidiasis in humans. This
      paper reports a systematic analysis of the putative glycosylphosphatidylinositol
      modified (GPI) proteins of C. glabrata, a large part of which are covalently
      bound to the cell wall glucan network and the remainder of which are retained in
      the plasma membrane, and of cell wall proteins (CWPs) which are covalently bound
      in a mild-alkali-sensitive manner. In silico genomic analysis revealed 106
      putative GPI proteins. Fifty-one of these GPI proteins could be categorized as
      adhesive proteins, potentially implicated in fungus-host interactions or biofilm
      formation during the development of fungal infections. Eleven proteins belonged
      to well-known GPI protein families of glycoside hydrolases, probably involved in
      cell wall expansion and remodelling during growth. Other identified GPI proteins
      included phospholipases, aspartic proteases, homologues of ScEcm33p and ScKre1p,
      and structural CWPs. Interestingly, the GPI algorithm predicted three orthologues
      of an abundant CWP in S. cerevisiae, Cwp1p, which is absent in Candida albicans.
      To evaluate the in silico predictions, isolated cell walls were extracted using
      HF-pyridine, which specifically cleaves phosphodiester bonds, to release GPI
      CWPs. Immunological analysis of the extract using one-dimensional SDS-PAGE and
      anti-ScCwp1p antiserum indicated the presence of a Cwp1p homologue in C. glabrata
      cell walls. Further analysis by two-dimensional gel electrophoresis and
      electrospray ionization tandem mass spectrometry (ESI-MS/MS) confirmed the
      presence of two of the predicted Cwp1p proteins, Cwp1.1p and Cwp1.2p. Crh1p, a
      putative 1,3-beta-glucan remodelling enzyme, was also identified. In silico
      genomic analysis further revealed five putative Pir proteins (Pir1-5p) and five
      members of the Bgl2 glycoside hydrolase family 17, belonging to a class of
      putative CWPs that can be extracted with NaOH. Immunological analysis of mild
      alkali-extracted CWPs showed the presence of a ScPir2p homologue. Together, these
      experimental data and in silico predictions represent the first systematic
      analysis of the C. glabrata cell wall proteome.

PMID- 15470095
TI  - Increased mortality of Saccharomyces cerevisiae cell wall protein mutants.
AB  - The yeast cell wall contains an unusually high number of different mannoproteins.
      The physiological role of most of them is unknown and gene disruptions leading to
      depletion of different proteins do not affect major functions of the wall. In
      this work the phenotype of different single and multiple cell wall protein
      mutants was observed at the level of individual cells. It was found that the lack
      of the non-covalently bound wall proteins Scw4p, Scw10p and Bgl2p increases the
      mortality of Saccharomyces cerevisiae cells grown exponentially under standard
      laboratory conditions, as assayed by methylene blue staining. Mutation of SCW11,
      however, suppressed the phenotype of scw4scw10, or scw4scw10bgl2, indicating that
      Scw4p, Scw10p and Bgl2p act synergistically while Scw11p has an activity
      antagonistic to that of the other three proteins. Mutants lacking major
      covalently bound proteins, either all four described Pir-proteins or the five
      most abundant glycosylphosphatidylinositol (GPI)-anchored proteins (Ccw12p,
      Ccw13p/Dan1p, Ccw14p/Icwp1p, Tip1p and Cwp1p), also had increased mortalities,
      the first somewhat more and the latter less than that of scw4scw10bgl2. In all
      cases the observed phenotype was suppressed by the addition of an osmotic
      stabilizer to the growth medium, indicating that cells died due to decreased
      osmotic stability. If cells were grown to stationary phase, Scw-mutants showed
      only slightly increased mortality, but mutants lacking Pir- or GPI-anchored
      proteins had significantly increased sensitivity, suggesting that their
      physiological function is primarily expressed in stationary-phase cells. In many
      cases structures consisting of a living ccw5ccw6ccw7ccw8 (multiple Pir-protein
      mutant) mother with two methylene blue-stained daughters could be seen.

PMID- 15470096
TI  - Role of Pir1 in the construction of the Candida albicans cell wall.
AB  - Searches in a Candida albicans database (http://genolist.pasteur.fr/CandidaDB/)
      identified two Individual Protein Files (IPF 15363 and 19968) whose deduced amino
      acid sequences showed 42 % and 45 % homology with Saccharomyces cerevisiae Pir4.
      The two DNA sequences are alleles of the same gene (CaPIR1) but IPF 19968 has a
      deletion of 117 bases. IPF 19968 encodes a putative polypeptide of 364 aa, which
      is highly O-glycosylated and has an N-mannosylated chain, four cysteine residues
      and seven repeats. Both alleles are expressed under different growth conditions
      and during wall construction by regenerating protoplasts. The heterozygous mutant
      cells are elongated, form clumps of several cells and are hypersensitive to drugs
      that affect cell wall assembly. CaPir1 was labelled with the V5 epitope and found
      linked to the 1,3-beta-glucan of the C. albicans wall and also by disulphide
      bridges when expressed in S. cerevisiae.

PMID- 15470097
TI  - Rot1p of Saccharomyces cerevisiae is a putative membrane protein required for
      normal levels of the cell wall 1,6-beta-glucan.
AB  - Although ROT1 is essential for growth of Saccharomyces cerevisiae strain BY4741,
      the growth of a rot1Delta haploid was partially restored by the addition of 0.6 M
      sorbitol to the growth medium. Rot1p is predicted to contain 256 amino acids, to
      have a molecular mass of 29 kDa, and to possess a transmembrane domain near its C
      terminus. Candida albicans and Schizosaccharomyces pombe have Rot1p homologues
      with high identity that also have predicted transmembrane domains. To explore the
      role of Rot1p, the phenotypes of the rot1Delta haploid were analysed. Deletion of
      ROT1 caused cell aggregation and an abnormal morphology. Analysis of the cell
      cycle showed that rot1Delta cells are delayed at the G2/M phase. The rot1Delta
      cells were resistant to K1 killer toxin and hypersensitive to SDS and hygromycin
      B, suggesting that they had cell wall defects. Indeed, greatly reduced levels of
      alkali-soluble and -insoluble 1,6-beta-glucan, and increased levels of chitin and
      1,3-beta-glucan, were found in rot1Delta cells. Furthermore, the phenotypes of
      rot1Delta cells resemble those of disruption mutants of the KRE5 and BIG1 genes,
      which show greatly reduced levels of cell wall 1,6-beta-glucan. Incorporation of
      glycosylphosphatidylinositol (GPI)-dependent cell wall proteins in big1Delta and
      rot1Delta cells was examined using a GFP-Flo1 fusion protein. GFP fluorescence
      was detected both on the cell surface and in the culture medium, suggesting that,
      in these mutants, mannoproteins may become only weakly bound to the cell wall and
      some of these proteins are released into the medium. Electron microscopic
      analyses of rot1Delta and big1Delta cells showed that the electron-dense
      mannoprotein rim staining was more diffuse and paler than that in the wild-type,
      and that the outer boundary of the cell wall was irregular. A big1Deltarot1Delta
      double mutant had a growth rate similar to the corresponding single mutants,
      suggesting that Rot1p and Big1p have related functions in 1,6-beta-glucan
      synthesis.

PMID- 15470098
TI  - Role of chitin synthase genes in Fusarium oxysporum.
AB  - Three structural chitin synthase genes, chs1, chs2 and chs3, were identified in
      the genome of Fusarium oxysporum f. sp. lycopersici, a soilborne pathogen causing
      vascular wilt disease in tomato plants. Based on amino acid identities with
      related fungal species, chs1, chs2 and chs3 encode structural chitin synthases
      (CSs) of class I, class II and class III, respectively. A gene (chs7) encoding a
      chaperone-like protein was identified by comparison of the deduced protein with
      Chs7p from Saccharomyces cerevisiae, an endoplasmic reticulum (ER) protein
      required for the export of ScChs3p (class IV) from the ER. So far no CS gene
      belonging to class IV has been isolated from F. oxysporum, although it probably
      contains more than one gene of this class, based on the genome data of the
      closely related species Fusarium graminearum. F. oxysporum chs1-, chs2- and chs7
      deficient mutants were constructed through targeted gene disruption by homologous
      recombination. No compensatory mechanism seems to exist between the CS genes
      studied, since chitin content determination and expression analysis of the chs
      genes showed no differences between the disruption mutants and the wild-type
      strain. By fluorescence microscopy using Calcofluor white and DAPI staining, the
      wild-type strain and Deltachs2 and Deltachs7 mutants showed similar septation and
      even nuclear distribution, with each hyphal compartment containing only one
      nucleus, whereas the Deltachs1 mutant showed compartments containing up to four
      nuclei. Pathogenicity assays on tomato plants indicated reduced virulence of
      Deltachs2 and Deltachs7 null mutants. Stress conditions affected normal
      development in Deltachs2 but not in Deltachs1 or Deltachs7 disruptants, and the
      three chs-deficient mutants showed increased hyphal hydrophobicity compared to
      the wild-type strain when grown in sorbitol-containing medium. The chitin
      synthase mutants will be useful for elucidating cell wall biogenesis in F.
      oxysporum and the relationship between fungal cell wall integrity and
      pathogenicity.

PMID- 15470099
TI  - Interspore bridges: a new feature of the Saccharomyces cerevisiae spore wall.
AB  - The Saccharomyces cerevisiae spore wall is a multilaminar coat that surrounds
      individual spores and protects them from environmental insult. Scanning electron
      microscopy reveals that the four spores of an ascus are connected by interspore
      bridges. Transmission electron microscopy of spores indicates that these bridges
      are continuous with the outer layers of the spore wall. In chs3 mutants, which
      lack the chitosan and dityrosine layers of the spore wall, bridges are absent. By
      contrast, in dit1 mutants, which lack only the dityrosine layer, bridges are
      present, suggesting that the bridges may be composed of chitosan. Interspore
      bridges are shown to be necessary to hold spores together after release from the
      ascus. A function for these bridges in the maintenance of heterozygous markers in
      a homothallic yeast population is proposed.

PMID- 15470100
TI  - Scw10p, a cell-wall glucanase/transglucosidase important for cell-wall stability
      in Saccharomyces cerevisiae.
AB  - Glycosyl hydrolases and transferases are crucial for the formation of a rigid but
      at the same time plastic cell wall in yeasts and fungi. The Saccharomyces
      cerevisiae glucan hydrolase family 17 (GH17) contains the soluble cell-wall
      proteins Scw4p, Scw10p, Scw11p and Bgl2p. For Bgl2p,
      endoglucanase/glucanosyltransferase activity has been demonstrated, and Scw11p
      has been shown to be involved in cell separation. Here, Scw4p and Scw10p, which
      show 63 % amino acid identity, were characterized. scw4 and scw10 single mutants
      were sensitive towards cell-wall destabilizing agents, suggesting a role in cell
      wall assembly or maintenance. Simultaneous deletion of SCW4 and SCW10 showed a
      synergistic effect, and activated the cell-wall compensatory mechanism in a PKC1
      dependent manner. Both the amount of cell-wall chitin and the amount of
      mannoproteins attached to chitin were increased in mutant scw4scw10. Deletion of
      CHS3 proved the critical role of chitin in scw4scw10. However, the mannoprotein
      Sed1p and the glucan synthase Fks2p were also crucial for cell-wall stability in
      mutant scw4scw10. The exchange of two conserved glutamate residues localized in
      the putative catalytic domain of GH17 family members strongly suggests that
      Scw10p acts as a 1,3-beta-glucanase or as a 1,3-beta-glucanosyltransferase. In
      addition, the synthetic interactions between Bgl2p and Scw10p which support a
      functional cooperation in cell-wall assembly were analysed. The data suggest that
      Scw4p and Scw10p act as glucanases or transglucosidases in concert with other
      cell-wall proteins to assure cell-wall integrity.

PMID- 15470101
TI  - Yeast Kre1p is GPI-anchored and involved in both cell wall assembly and
      architecture.
AB  - Kre1p is a cell surface O-glycoprotein involved in a late stage of 1,6-beta
      glucan formation in the yeast Saccharomyces cerevisiae. Disruption of KRE1 leads
      to a 40 % reduction in the overall 1,6-beta-glucan content of the cell wall. This
      paper shows that in a yeast Deltakre1 null mutant, neither an N-terminal
      truncated Kre1p nor Kre1p variants lacking a C-terminal
      glycosylphospatidylinositol (GPI) attachment site are capable of achieving normal
      function in glucan assembly, while full-length Kre1p completely complements a
      Deltakre1 null mutation and restores cell wall 1,6-beta-glucan content up to wild
      type level. In a yeast gpi1 mutant, a green-fluorescent-protein-tagged Kre1p
      derivative is secreted into the medium, indicating an at least transient GPI
      anchoring stage of Kre1p during its processing within the yeast secretory
      pathway. In contrast to the severe defect in cell wall beta-d-glucan, the amount
      of cell wall mannoproteins is not significantly decreased in a Deltakre1
      disruptant, as could be confirmed in competition assays by investigating toxin
      binding to isolated cell wall mannoproteins. Since the yeast Deltakre1 mutant
      differed in its sensitivity to zygocin and K28, two killer viral protein toxins
      that use different cell wall mannoprotein populations as a primary toxin
      receptor, it can be concluded that in a yeast Deltakre1 background, mannoproteins
      do not differ significantly in total amount from a Kre1+ wild-type but rather in
      their expression and distribution at the cell surface. Taken together, these data
      favour and suggest a structural, rather than enzymic, function of Kre1p in yeast
      cell wall assembly.

PMID- 15470102
TI  - The ER-Golgi v-SNARE Bet1p is required for cross-linking alpha-agglutinin to the
      cell wall in yeast.
AB  - In Saccharomyces cerevisiae, glycosylphosphatidylinositol (GPI)-anchored cell
      wall mannoproteins, including alpha-agglutinin, are secreted to the cell surface
      through vesicular transport pathways. At the cell surface the GPI anchors are
      cleaved within the glycan, then transglycosylated to form a covalent cross-link
      to 1,6-beta-glucan. Among mutants that were temperature-sensitive for growth and
      for ability to cross-link the mannoprotein alpha-agglutinin to the cell wall, one
      strain was complemented by BET1, which encodes an ER-Golgi v-SNARE. Temperature
      sensitive mutations in BET1 caused aberrations in cell wall structure, including
      excretion of alpha-agglutinin into the medium, sensitivity to lysis with
      Zymolyase and hypersensitivity to Calcofluor White. At restrictive temperatures,
      bet1 mutations block secretion of invertase and other proteins, but alpha
      agglutinin was excreted into the extracellular medium. In wild-type parental or
      bet1 cells, secretion of alpha-agglutinin also continued after protein synthesis
      was blocked with cycloheximide. This secretion was due to continued export of a
      significant amount of alpha-agglutinin from compartments distal to the BET1
      dependent secretion step. Thus, in bet1 cells the ER-Golgi block allowed
      secretion to continue, but prevented cell wall incorporation of the alpha
      agglutinin. Therefore, a mutation early in the secretion pathway caused aberrant
      cell wall synthesis by preventing localization of key components required in wall
      cross-links.

PMID- 15470103
TI  - Saccharomyces cerevisiae Bni4p directs the formation of the chitin ring and also
      participates in the correct assembly of the septum structure.
AB  - In Saccharomyces cerevisiae cytokinesis is efficiently achieved when a concerted
      series of events take place at the neck region, leading to septum formation. Here
      it is shown that Bni4p plays a crucial role in this process. Deltabni4 mutants
      contain normal amounts of chitin and show normal chitin synthase III (CSIII)
      activity, but are partially resistant to Calcofluor White (CFW), probably due to
      the striking pattern of chitin distribution. CFW vital staining shows that chitin
      is synthesized in daughter cells and that it is also asymmetrically deposited at
      the mother-side of the neck in large-budded cells. This specific pattern
      coincides with that of Chs4p and Chs3p proteins. Alternatively, staining of
      unbudded cultures confirmed that Bni4p directs early chitin ring assembly, but is
      no longer required for the chitin deposition that occurs late in the cell cycle
      at cytokinesis. Consequently, this work provides a strategy to genetically
      discriminate between the absence of chitin synthesis (Deltachs3 mutant) and
      failure in chitin ring assembly (Deltabni4 mutants). The characterization of
      double mutants affected in chitin synthesis and primary septum (PS) assembly
      (Deltamyo1 and Deltachs2) provides evidence for the cooperation of Bni4p in PS
      formation besides its role in chitin ring assembly. In addition, it is shown that
      the chitin ring, but not the late deposition of chitin, cooperates in the correct
      assembly of the actomyosin ring and the PS when the biological function of the
      septins is compromised. We conclude that Bni4p is not only required for the
      assembly of the chitin ring, but is also involved in septum architecture and the
      maintenance of neck integrity.

PMID- 15470104
TI  - Candida albicans mutants in the BNI4 gene have reduced cell-wall chitin and
      alterations in morphogenesis.
AB  - The Candida albicans BNI4 gene was identified by homology to the Saccharomyces
      cerevisiae orthologue and encodes a predicted 1655 amino acid protein. In S.
      cerevisiae most cell-wall chitin is associated with primary septum formation and
      Bni4p is involved in tethering the Chs3p chitin synthase enzyme to the mother-bud
      neck by forming a bridge between a regulatory protein Chs4p and the septin
      Cdc10p. CaBni4p shows 20 % overall identity to the ScBni4p, with 73 % identity
      over the C-terminal 63 amino acids, which includes a putative protein phosphatase
      type 1 (PP1) binding domain. Northern blot analysis revealed a transcript of the
      expected size that was expressed in both yeast and hyphal growth forms. C.
      albicans has more chitin in its cell wall than S. cerevisiae, and again most
      chitin is synthesized by CaChs3p. The function of CaBNI4 was investigated by
      performing a targeted gene disruption using the 'Ura-blaster' method to delete
      amino acids 1120-1611 that are essential for function. The resulting
      Cabni4Delta/Cabni4Delta null mutants formed lemon-shaped yeast cells and had a 30
      % reduction in cell-wall chitin, reduced hyphal formation on solid serum
      containing medium and increased sensitivity to SDS and increased resistance to
      Calcofluor White. The Cabni4Delta/Cabni4Delta null mutants were unaffected in
      chitin ring formation, but often exhibited displaced bud sites with more obvious
      but flattened birth scars. Therefore, unlike in S. cerevisiae, the Cabni4 mutant
      apparently alters chitin distribution throughout the cell wall and not
      exclusively at the bud-neck region.

PMID- 15470105
TI  - Survival and cytokinesis of Saccharomyces cerevisiae in the absence of chitin.
AB  - Most fungal cell walls are constructed with significant amounts of chitin, a
      linear polysaccharide that contributes mechanical resistance to the structure. In
      the yeast Saccharomyces cerevisiae, chitin is synthesized by three different
      isozymes, each of which has a separate cellular function. In this yeast, the most
      important role of chitin is in cytokinesis, when a thin primary septum is
      synthesized by chitin synthase II to separate mother and daughter cells. If no
      primary septum can be formed, an irregular remedial septum is synthesized, a
      process that relies on chitin synthase III. It was found that, with osmotic
      stabilization, S. cerevisiae tolerates a loss of all chitin synthase activities.
      Chitin-deficient mutants display a cytokinesis defect which leads to the
      formation of cell chains with incompletely separated cytoplasms. In these mutants
      septa are formed rarely. The few septa found are bulky structures which contain
      inclusions of cytoplasm. Nuclear division proceeds under these conditions,
      demonstrating that there is no cell cycle arrest triggered by a failure to form a
      septum between mother and daughter cell. A genetic suppressor arises quickly in
      chitin-deficient mutants, giving rise to the synthesis of chitin-free remedial
      septa. The suppressed chitin-free mutants grow well without osmotic stabilization
      and display hyper-resistance against the chitin-synthase inhibitor polyoxin D.

PMID- 15470106
TI  - The Aspergillus fumigatus cell wall is organized in domains that are remodelled
      during polarity establishment.
AB  - Aspergillus fumigatus is a life-threatening and increasingly frequent pathogen of
      the immunocompromised. Like other filamentous fungi A. fumigatus grows in a
      highly polar manner, adding new cell wall to the apical region of hyphae. mAbs
      were raised against isolated A. fumigatus cell walls. Fifteen antibodies bound
      reproducibly to isolated cell walls in ELISAs and to the walls of intact cells in
      immunofluorescence experiments. Surprisingly, individual mAbs showed distinct
      patterns of localization. Six antibodies labelled exclusively conidial or basal
      regions, seven labelled apical regions and a single antibody labelled both basal
      and apical regions of hyphae. Ten antibodies did not label the walls adjacent to
      septa. In double labelling experiments with representative mAbs there was little
      or no overlap between epitopes recognized. These labelling patterns suggest that
      the wall is made up of basal and apical domains that differ in composition or
      organization and that the wall region flanking septa differs from other regions
      of the lateral wall. In time-course experiments of early A. fumigatus growth,
      mAb16C4 failed to label isotropically expanding cells and labelled emerging germ
      tubes and branches. The same mAb failed to label the Aspergillus nidulans swoC
      mutant, which is defective in polarity establishment. However, mAb16C4 did label
      the A. nidulans swoA mutant, which completes polarity establishment, but is
      defective in polarity maintenance. Thus, mAb16C4 appears to recognize a cell wall
      change that occurs during polarity establishment. In immunogold labelling and
      transmission electron microscopy (TEM) experiments, conidia, basal regions and
      apical regions of thin-sectioned cells labelled with mAb16C4. That only apical
      regions labelled in intact cells (immunofluorescence) while conidial, basal and
      apical regions labelled in thin-sectioned cells (TEM) suggests that the 16C4
      epitope is present along the whole hypha, but is masked everywhere except the tip
      until polarity establishment. That is to say, some remodelling of the wall during
      polarity establishment exposes the 16C4 epitope. The 16C4 epitope was partially
      purified from A. fumigatus total protein by passage through hydrophobic
      interaction and anion-exchange columns. The resulting single ELISA-positive
      fraction showed relatively few bands by SDS-PAGE and silver staining and a strong
      band by Western blotting with the16C4 mAb. Sequencing of the fraction yielded a
      predicted peptide with a 6-amino acid exact match to a region of the Cat1 protein
      previously identified as an immunodominant A. fumigatus catalase that localizes
      to the cell wall and is secreted to the medium. Experiments are under way to
      determine if mAb16C4 recognizes Cat1 or another protein that co-purifies with
      Cat1.

PMID- 15470107
TI  - CRR1, a gene encoding a putative transglycosidase, is required for proper spore
      wall assembly in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, sporulation is a developmental process that converts
      a single cell into four haploid spores. The four haploid nuclei are encapsulated
      within multilayered spore walls that protect them against stressful conditions.
      The formation of the spore-specific cell wall is a highly coordinated process
      that requires the participation of enzymic activities for biosynthesis,
      degradation, and cross-linking between components. Here the sporulation-specific
      gene CRR1, encoding a putative transglycosidase that is required for proper spore
      wall assembly, is described. Both the transcription of CRR1 and the synthesis of
      Crr1p were induced biphasically under sporulating conditions, with a first
      expression peak displaying kinetics similar to those of the middle to middle-late
      sporulation-specific genes, and a second late peak after 24 h under these
      conditions. Localization studies revealed that Crr1p localized to the spore wall
      that surrounds each of the four ascospores within the mature asci. Mutation of
      this gene had no effect on the efficiency of spore formation. However, crr1
      mutant spores were sensitive to hydrolytic enzymes such as glusulase and to heat
      shock treatments, underscoring the importance of this gene in the proper
      formation and assembly of the ascospore wall. Moreover, the deletion of CRR1 had
      additive effects with respect to the sensitivity of cda1 cda2 mutants to these
      treatments. Interestingly, overexpression of CRR1 not only complemented the
      phenotype of the crr1 strain but also rendered spores more resistant to the
      stress conditions than the wild-type. Like other mutants impaired in the
      formation of the spore outer layer, crr1 mutants were permeable to Calcofluor
      White. Finally, detailed analysis by electron microscopy of the spore walls in
      the crr1 mutants revealed a defect in the assembly of the spore wall components,
      suggesting a role for Crr1p in the cross-linking between the inner
      (glucan/mannoprotein) and the outer (chitosan/dityrosine) spore layers.

PMID- 15470108
TI  - Mutational analysis of the cytoplasmic domain of the Wsc1 cell wall stress
      sensor.
AB  - Wsc1 is a member of a family of highly O-glycosylated cell surface proteins that
      reside in the plasma membrane of Saccharomyces cerevisiae and function as sensors
      of cell wall stress. These proteins activate the cell wall integrity signalling
      pathway by stimulating the small G-protein Rho1, protein kinase C (Pkc1) and a
      MAP kinase cascade. The cytoplasmic domains of Wsc1 family members interact with
      the Rom2 guanine nucleotide exchange factor to stimulate GTP-binding of Rho1.
      Here, a mutational analysis of the cytoplasmic domain of Wsc1 is presented. The
      data identify two regions of the Wsc1 cytoplasmic tail that are conserved with
      other family members as important for Rom2 interaction. These regions are
      separated by an inhibitory region, which includes a cluster of seryl residues
      that appear to be phosphorylated. Mutational analysis of these residues supports
      a model in which Wsc1 interaction with Rom2 is negatively regulated by
      phosphorylation.

PMID- 15470109
TI  - Differential roles of PDK1- and PDK2-phosphorylation sites in the yeast AGC
      kinases Ypk1, Pkc1 and Sch9.
AB  - Saccharomyces cerevisiae Pkh1 and Pkh2 (orthologues of mammalian protein kinase,
      PDK1) are functionally redundant. These kinases activate three AGC family kinases
      involved in the maintenance of cell wall integrity: Ypk1 and Ypk2, two closely
      related, functionally redundant enzymes (orthologues of mammalian protein kinase
      SGK), and Pkc1 (orthologue of mammalian protein kinase PRK2). Pkh1 and Pkh2
      activate Ypk1, Ypk2 and Pkc1 by phosphorylating a Thr in a conserved sequence
      motif (PDK1 site) within the activation loop of these proteins. A fourth protein
      kinase involved in growth control and stress response, Sch9 (orthologue of
      mammalian protein kinase c-Akt/PKB), also carries the conserved activation loop
      motif. Like other AGC family kinases, Ypk1, Ypk2, Pkc1 and Sch9 also carry a
      second conserved sequence motif situated in a region C-terminal to the catalytic
      domain, called the hydrophobic motif (PDK2 site). Currently, there is still
      controversy surrounding the identity of the enzyme responsible for
      phosphorylating this second site and the necessity for phosphorylation at this
      site for in vivo function. Here, genetic and biochemical methods have been used
      to investigate the physiological consequences of phosphorylation at the PDK1 and
      PDK2 sites of Ypk1, Pkc1 and Sch9. It was found that phosphorylation at the PDK1
      site in the activation loop is indispensable for the essential functions of all
      three kinases in vivo, whereas phosphorylation at the PDK2 motif plays a non
      essential and much more subtle role in modulating the ability of these kinases to
      regulate the downstream processes in which they participate.

PMID- 15470110
TI  - Studies on the regulation of the two-component histidine kinase gene CHK1 in
      Candida albicans using the heterologous lacZ reporter gene.
AB  - The two-component histidine kinase Chk1p of Candida albicans has been implicated
      in the regulation of cell wall biosynthesis. Deletion of CHK1 results in
      avirulence that in part may be due to the increased sensitivity of mutant strains
      to polymorphonuclear leukocytes. The mutant also does not adhere to human
      oesophageal tissue in vitro, probably as a consequence of its altered cell wall.
      In the current study, a CHK1 promoter-lacZ reporter (CHK1prlacZ) construct was
      expressed in wild-type C. albicans strain CAI4 and in two-component signal
      transduction mutants to determine the effect of environmental stress conditions
      on the regulation of CHK1 and the co-regulatory activities among these proteins.
      It is shown that lacZ expression varied according to the type of growth
      conditions and incubation time; expression was also influenced by the strain
      background. lacZ expression in CAI4 was greater at 37 degrees C and at a pH of
      3.5 and in the presence of 4 mM H2O2, 0.1 mM menadione, 10 % serum or 1.5 M NaCl
      compared to cells grown at 30 or 42 degrees C. The increases in expression were
      time-dependent and not observed until cells were incubated for 120 min in these
      conditions (P < 0.05). As a correlate of the increase in transcription of CHK1
      lacZ in the presence of H2O2, the chk1 mutant was more sensitive than wild-type
      and revertant cells to H2O2 in vitro. In addition to strain CAI4, we also
      measured CHK1p-lacZ reporter activity of mutants deleted in genes encoding other
      two-component proteins such as the response regulator gene SSK1, the histidine
      kinases, SLN1 and NIK1, and the HOG1 MAP kinase. Of these proteins, Ssk1p and
      Sln1p are presumed to mediate phosphotransfer to the HOG1 [hyperosmotic glycerol]
      MAP kinase pathway during oxidative and perhaps osmotic stress in C. albicans.
      Compared to strain CAI4, lacZ reporter activity increased significantly in the
      ssk1 mutant under all growth conditions after a 10 and 120 min incubation (P <
      0.0001). lacZ expression in the ssk1 mutant was less at 42 degrees C compared to
      all other growth conditions (P < 0.05). Furthermore, lacZ reporter activity also
      increased in the hog1 mutant of C. albicans. These data suggest that SSK1 and
      HOG1 indirectly or directly negatively regulate CHK1 under most growth conditions
      tested. In the sln1 mutant, downregulation of CHK1 was observed in all growth
      conditions compared to strain CAI4 (P < 0.05), while regulation of lacZ in the
      nik1 mutant was similar to strain CAI4 except when cells were incubated in the
      presence of 4 mM H2O2 for 120 min (P < 0.05). Western blot analysis was used to
      determine the role of Chk1p in phosphorylation of Hog1p under oxidative or
      osmotic stress. It was found that Hog1p was phosphorylated in the chk1 mutant
      similar to wild-type CAF2-1 cells, although the temporal events of
      phosphorylation differed slightly in mutant cells. These results show that
      transcription of CHK1, as measured by the lacZ reporter assay, is statistically
      increased when cells are exposed to several types of stress or when incubated in
      10 % serum in a mutant-specific background and at a specific time point. Of
      importance, our data also suggest that lacZ expression is indirectly or directly
      regulated by the HOG1 MAP kinase pathway, although a determination of its
      position in this pathway or in a cross-talking pathway awaits additional studies.

PMID- 15470111
TI  - The cell wall stress response in Aspergillus niger involves increased expression
      of the glutamine : fructose-6-phosphate amidotransferase-encoding gene (gfaA) and
      increased deposition of chitin in the cell wall.
AB  - Perturbation of cell wall synthesis in Saccharomyces cerevisiae, either by
      mutations in cell wall synthesis-related genes or by adding compounds that
      interfere with normal cell wall assembly, triggers a compensatory response to
      ensure cell wall integrity. This response includes an increase in chitin levels
      in the cell wall. Here it is shown that Aspergillus niger also responds to cell
      wall stress by increasing chitin levels. The increased chitin level in the cell
      wall was accompanied by increased transcription of gfaA, encoding the glutamine :
      fructose-6-phosphate amidotransferase enzyme, which is responsible for the first
      and a rate-limiting step in chitin synthesis. Cloning and disruption of the gfaA
      gene in A. niger showed that it was an essential gene, but that addition of
      glucosamine to the growth medium could rescue the deletion strain. When the plant
      pathogenic fungus Fusarium oxysporum and food spoilage fungus Penicillium
      chrysogenum were subjected to cell wall stress, the transcript level of their gfa
      gene increased as well. These observations suggest that cell wall stress in fungi
      may generally lead to activation of the chitin biosynthetic pathway.

PMID- 15470112
TI  - Impaired PRPP-synthesizing capacity compromises cell integrity signalling in
      Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, PRS genes comprise a family of five paralogous
      genes. Previously, it has been shown that in the cell the gene products are
      organized into two interacting complexes, one of which is a heterodimer and the
      other a heterotrimer. Here, it has been demonstrated that in addition to
      supplying the cell with the key metabolic intermediate PRPP [5-phospho-D-ribosyl
      1(alpha)-pyrophosphate], the gene products contribute to the maintenance of cell
      integrity. Specifically, the phosphorylation of Rlm1, one of the end points of
      the cell integrity signalling pathway, is significantly impaired following
      deletion of any one of the PRS genes, in particular PRS1 and PRS3. This is
      reflected in changes in the expression of the alternative 1,3-beta-glucan
      synthase catalytic subunit, Fks2, as measured by its promoter activity. Yeast two
      hybrid analysis has shown that Prs1, specifically the non-homologous region, NHR1
      1 and Prs3, and to a lesser extent Prs2 and Prs4, interact with the MAPK (mitogen
      activated protein kinase) of the cell integrity pathway, Slt2. When PRS1 is
      lacking, the basal level of phosphorylation of Slt2 is increased. Furthermore,
      prs1Delta and prs3Delta strains have an increased chitin content under normal
      growth conditions. alpha-Factor sensitivity and Calcofluor White resistance
      associated with the lack of Prs1 and Prs3 corroborate the involvement of these
      two gene products in cell integrity signalling. It is postulated that Prs
      polypeptides play a significant role in the remodelling of the cell wall and may
      have a direct involvement in cell integrity signalling.

PMID- 15470113
TI  - The GPI-anchored protein CaEcm33p is required for cell wall integrity,
      morphogenesis and virulence in Candida albicans.
AB  - Ecm33p is a widely distributed fungal protein with functional relevance, clearly
      demonstrated by ecm33Delta mutant phenotypes, mainly related to the cell wall.
      Homology searches with Saccharomyces cerevisiae genes identified Candida albicans
      Ecm33p, as well as the two other proteins of its family: Pst1p and the product of
      YCL048w. C. albicans Ecm33p is a 423 aa protein which has the typical features of
      cell-surface GPI proteins and is able to complement S. cerevisiae ecm33Delta cell
      wall defects. Heterozygous (RML1) and homozygous (RML2) mutants of CaECM33 were
      obtained, as well as a single and a double reintegrant (RML3 and RML4,
      respectively). Caecm33 mutant strains displayed an aberrant morphology, being
      more rounded and bigger than the wild-type, suggesting morphogenetic defects.
      They also exhibited cell wall defects, with enhanced sensitivity to different
      compounds that interfere in polymerization of cell wall components (Calcofluor
      white, Congo red and hygromycin B) and a marked tendency to flocculate
      extensively. In addition, CaEcm33p is required for normal C. albicans yeast-to
      hyphae transition in vitro. In liquid medium (5 % serum), the transition was
      delayed in Caecm33 mutants, and after 24 h the culture contained very abnormal
      large and rounded cells. On solid medium (10 % serum, Spider or SLADH) RML2
      failed to produce hyphae and media invasiveness. CaECM33 showed a gene dosage
      effect, demonstrated by the intermediate phenotype of the heterozygous mutants
      RML1 and confirmed by Northern blot analysis. Furthermore, CaEcm33p is also
      involved in C. albicans virulence. In a murine systemic model of infection, 100 %
      mouse survival and no kidney or brain colonization were obtained 30 days after
      infection with 10(6) Candida cells of any homozygous or heterozygous Caecm33Delta
      mutant tested. In contrast, all mice infected with parental or RML4 (two CaECM33
      copies reintegrated) strains died in a few days, showing that, in these
      conditions, two CaECM33 copies were required for virulence.

PMID- 15470114
TI  - Ectophosphatase activity in conidial forms of Fonsecaea pedrosoi is modulated by
      exogenous phosphate and influences fungal adhesion to mammalian cells.
AB  - A cell-wall-associated phosphatase in hyphae of Fonsecaea pedrosoi, a fungal
      pathogen causing chromoblastomycosis, was previously characterized by the
      authors. In the present work, the expression of an acidic ectophosphatase
      activity in F. pedrosoi conidial forms was investigated. The surface phosphatase
      activity in F. pedrosoi is associated with the cell wall, as demonstrated by
      transmission electron microscopy. This enzyme activity was strongly inhibited by
      exogenous inorganic phosphate (P(i)). Accordingly, removal of P(i) from the
      culture medium of F. pedrosoi resulted in a marked (130-fold) increase of
      ectophosphatase activity. With the artificial phosphatase substrate p-nitrophenyl
      phosphate, a Km value of 0.63+/-0.04 mM was estimated for the phosphatase
      activity of fungal cells strongly expressing the enzyme activity. This enzyme
      activity was not modulated by cations. Conidia with greater ectophosphatase
      activity showed greater adherence to mammalian cells than did fungi cultivated in
      the presence of P(i) (low phosphatase activity). Surface phosphatase activity was
      apparently involved in the adhesion to host cells, since the enhanced attachment
      of F. pedrosoi to host cells was reversed by pre-treatment of conidia with
      phosphatase inhibitor. Since conidial forms are the putative infectious
      propagules in chromoblastomycosis, the expression and activity of acidic surface
      phosphatases in these cells may contribute to the early mechanisms required for
      disease establishment.

PMID- 15470115
TI  - Comparative genomics using Candida albicans DNA microarrays reveals absence and
      divergence of virulence-associated genes in Candida dubliniensis.
AB  - Candida dubliniensis is a pathogenic yeast species closely related to Candida
      albicans. However, it is less frequently associated with human disease and
      displays reduced virulence in animal models of infection. Here comparative
      genomic hybridization was used in order to assess why C. dubliniensis is
      apparently less virulent than C. albicans. In these experiments the genomes of
      the two species were compared by co-hybridizing C. albicans microarrays with
      fluorescently labelled C. albicans and C. dubliniensis genomic DNA. C.
      dubliniensis genomic DNA was found to hybridize reproducibly to 95.6 % of C.
      albicans gene-specific sequences, indicating a significant degree of nucleotide
      sequence homology (> 60 %) in these sequences. The remaining 4.4 % of sequences
      (representing 247 genes) gave C. albicans/C. dubliniensis normalized fluorescent
      signal ratios that indicated significant sequence divergence (< 60 % homology) or
      absence in C. dubliniensis. Sequence divergence was identified in several genes
      (confirmed by Southern blot analysis and sequence analysis of PCR products) with
      putative virulence functions, including the gene encoding the hypha-specific
      human transglutaminase substrate Hwp1p. Poor hybridization of C. dubliniensis
      genomic DNA to the array sequences for the secreted aspartyl proteinase-encoding
      gene SAP5 also led to the finding that SAP5 was absent in C. dubliniensis and
      that this species possesses only one gene homologous to SAP4 and SAP6 of C.
      albicans. In addition, divergence and absence of sequences in several gene
      families was identified, including a family of HYR1-like GPI-anchored proteins, a
      family of genes homologous to a putative transcriptional activator (CTA2) and
      several ALS genes. This study has confirmed the close relatedness of C. albicans
      and C. dubliniensis and has identified a subset of unique C. albicans genes that
      may contribute to the increased prevalence and virulence of this species.

PMID- 15470117
TI  - Amino acid residues involved in cold adaptation of isocitrate lyase from a
      psychrophilic bacterium, Colwellia maris.
AB  - To investigate the mechanism of cold adaptation of isocitrate lyase (ICL; EC
      4.1.3.1) from the psychrophilic bacterium Colwellia maris, Gln207 and Gln217 of
      this enzyme were substituted by His and Lys, respectively, by site-directed
      mutagenesis. His184 and Lys194 of ICL from Escherichia coli, corresponding to the
      two Gln residues of C. maris ICL, are highly conserved in the ICLs of many
      organisms and are known to be essential for catalytic function. The mutated ICLs
      (Cm-Q207H and Cm-Q217K, respectively) and wild-type enzymes of C. maris and E.
      coli (Cm-WT and Ec-WT) with His-tagged peptides were overexpressed in E. coli
      cells and purified to homogeneity. Thermolabile Cm-WT and mutated ICLs were
      susceptible to digestion with trypsin, while relatively thermostable Ec-WT was
      resistant to trypsin digestion, suggesting that the thermostability and
      resistance to tryptic digestion of the ICLs are related. Cm-Q207H and Cm-Q217K
      showed specific activities similar to Cm-WT at temperatures between 30 degrees C
      and 40 degrees C, but their activities between 10 degrees C and 25 degrees C were
      decreased, indicating that the two Gln residues of the C. maris ICL play
      important roles in its cold adaptation. Phylogenetic analysis of ICLs from
      various organisms revealed that the C. maris ICL can be categorized in a novel
      group, subfamily 3, together with several eubacterial ICLs.

PMID- 15470116
TI  - Stress induces depletion of Cdc25p and decreases the cAMP producing capability in
      Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae the cAMP-dependent protein kinase A pathway
      antagonizes the cellular response to stress. It is shown here that the cellular
      content of Cdc25p, the upstream activator of Ras and adenylyl cyclase, decays
      upon various stresses such as heat shock and oxidative and ethanol shocks,
      whereas its phosphorylation level and its localization are unaffected. In
      parallel with the reduction of Cdc25p, the maximal capacity of the cell to
      accumulate cAMP decreases when its feedback regulation is abolished. A deletion
      of CDC25 prevents this decrease. Paradoxically, in wild-type cells, with normal
      feedback regulation, the level of cAMP, which is much lower, is not reduced but
      is rather increased upon stress. These observations are consistent with a role of
      Cdc25p in sensing and transducing stress to downstream targets, either through a
      cAMP-independent pathway or by large fluctuations in the cAMP content of the
      cell.

PMID- 15470118
TI  - The role of polyhydroxyalkanoate biosynthesis by Pseudomonas aeruginosa in
      rhamnolipid and alginate production as well as stress tolerance and biofilm
      formation.
AB  - Pseudomonas aeruginosa is capable of synthesizing polyhydroxyalkanoic acids
      (PHAs) and rhamnolipids, both of which are composed of 3-hydroxydecanoic acids
      connected by ester bonds, as well as synthesizing the biofilm matrix polymer
      alginate. In order to study the influence of PHA biosynthesis on rhamnolipid and
      alginate biosynthesis, as well as stress tolerance and biofilm formation,
      isogenic knock-out mutants deficient in PHA biosynthesis were generated for P.
      aeruginosa PAO1 and the alginate-overproducing P. aeruginosa FRD1. A gentamicin
      resistance cassette was inserted replacing the 3' region of phaC1, the whole of
      phaZ and the 5' region of phaC2. Gas chromatography/mass spectrometry analysis
      showed that PHA accumulation was completely abolished in both strains.
      Interestingly, this gene replacement did not abolish rhamnolipid production.
      Thus, as previously suggested, the PHA synthase is not directly involved in
      rhamnolipid biosynthesis. In the PHA-negative mutant of mucoid FRD1 alginate
      biosynthesis was not affected, whereas in the PHA-negative PAO1 mutant an almost
      threefold increase in biosynthesis was observed compared to the wild-type.
      Consistently, PHA accumulation in FRD1 contributed only 4.7 % of cell dry weight,
      which is fourfold less than in PAO1. These data suggest that PHA biosynthesis and
      alginate biosynthesis are in competition with respect to a common precursor. The
      surface attachment and biofilm development of the PHA-negative mutants were also
      compared to those of wild-type strains in glass flow-cell reactors. PHA-negative
      mutants of P. aeruginosa PAO1 and FRD1 showed reduced attachment to glass.
      However, the PAO1 PHA-negative mutant, in contrast to the wild-type, formed a
      stable biofilm with large, distinct and differentiated microcolonies
      characteristic of alginate-overproducing strains of P. aeruginosa. The stress
      tolerance of PHA-negative mutants with respect to elevated temperature was
      strongly impaired. These data indicated a functional role for PHA in stress
      response and tolerance.

PMID- 15470119
TI  - Membrane topology and mutational analysis of Escherichia coli CydDC, an ABC-type
      cysteine exporter required for cytochrome assembly.
AB  - Cytochrome bd is a respiratory quinol oxidase in Escherichia coli. Besides the
      structural genes (cydA and cydB) encoding the oxidase complex, the cydD and cydC
      genes, encoding an ABC-type transporter, are required for assembly of this
      oxidase. Recently, cysteine has been identified as a substrate (allocrite) that
      is transported from the cytoplasm by CydDC, but the mechanism of cysteine export
      to the periplasm and its role there remain unknown. To initiate an understanding
      of structure-function relationships in CydDC, its membrane topography was
      analysed by generating protein fusions between random and selected residues in
      the two polypeptides with both alkaline phosphatase and beta-galactosidase. CydD
      and CydC are experimentally shown each to have six transmembrane segments, two
      major cytoplasmic loops and three minor periplasmic loops; both termini of each
      protein face the cytoplasm. The cydD1 allele is shown to have two point mutations
      (G319D, G429E) within the ATP-binding domain of CydD; either mutation alone is
      sufficient to cause loss or severe reduction of cytochrome bd assembly. A
      comparative sequence analysis prompted the targeting of residues in CydD for site
      directed mutational analysis, which identified (i) the 'start' methionine
      residue, (ii) essential residues in the ATP-binding site (Walker sequence A) and
      (iii) a duplicated positively charged heptameric motif, R-G/T-L/M-X-T/V-L-R, in
      CydD cytoplasmic loop II. The replacement of arginines in these motifs with
      glycines resulted in Cyd- phenotypes; however, activity could be restored at
      these positions by replacing the glycine with lysine or histidine and hence
      returning the positive charge. The conservation of these charges in CydD-like
      proteins indicates functional importance. Evolutionary aspects of bacterial cyd
      genes are discussed.

PMID- 15470120
TI  - Microbial community structure in a thermophilic anaerobic hybrid reactor
      degrading terephthalate.
AB  - A thermophilic terephthalate-degrading methanogenic consortium was successfully
      enriched for 272 days in an anaerobic hybrid reactor, and the microbial structure
      was characterized using terminal RFLPs, clone libraries and fluorescence in-situ
      hybridization with rRNA-targeted oligonucleotide probes. All the results
      suggested that Methanothrix thermophila-related methanogens, Desulfotomaculum
      related bacterial populations in the Gram-positive low-G + C group, and OP5
      related populations were the key members responsible for terephthalate
      degradation under thermophilic methanogenic conditions except during periods when
      the reactor experienced heat shock and pump failure. These perturbations caused a
      significant shift in bacterial population structure in sludge samples taken from
      the sludge bed but not from the surface of the packing materials. After system
      recovery, many other bacterial populations emerged, which belonged mainly to the
      Gram-positive low-G + C group and Cytophaga-Flexibacter-Bacteroides, as well as
      beta-Proteobacteria, Planctomycetes and Nitrospira. These newly emerged
      populations were probably also capable of degrading terephthalate in the hybrid
      system, but were out-competed by those bacterial populations before
      perturbations.

PMID- 15470121
TI  - GerE-independent expression of cotH leads to CotC accumulation in the mother cell
      compartment during Bacillus subtilis sporulation.
AB  - Evidence is presented that expression of the cotH gene, whose product is required
      for the correct assembly of the Bacillus subtilis spore coat, is negatively
      controlled by the transcriptional regulator GerE. Mutations in the GerE-box,
      present in the cotH promoter region, increased expression of this gene, which
      also remained elevated during late stages of sporulation, when in wild-type cells
      cotH is normally turned off. Such alterations of cotH expression did not
      significantly affect spore coat structure or function but caused the accumulation
      of CotC molecules in the mother cell compartment, most likely as a consequence of
      CotH-mediated protection of CotC.

PMID- 15470122
TI  - Detoxification of hydrogen peroxide and expression of catalase genes in
      Rhodobacter.
AB  - The two related facultatively photosynthetic bacteria Rhodobacter sphaeroides and
      Rhodobacter capsulatus show different sensitivities against peroxide stress. R.
      sphaeroides is able to tolerate higher concentrations of H2O2 and exhibits higher
      catalase activity than R. capsulatus. The katE gene of R. sphaeroides and the
      katG gene of R. capsulatus are strongly induced by H2O2. This induction depends
      on the presence of the OxyR protein, which is able to bind to the promoter
      regions of these genes. In addition to katE R. sphaeroides harbours the katC
      gene, which shows no significant response to H2O2 but is induced in stationary
      phase.

PMID- 15470123
TI  - Crotonyl-coenzyme A reductase provides methylmalonyl-CoA precursors for monensin
      biosynthesis by Streptomyces cinnamonensis in an oil-based extended fermentation.
AB  - It is demonstrated that crotonyl-CoA reductase (CCR) plays a significant role in
      providing methylmalonyl-CoA for monensin biosynthesis in oil-based 10-day
      fermentations of Streptomyces cinnamonensis. Under these conditions S.
      cinnamonensis L1, a derivative of a high-titre producing industrial strain C730.1
      in which ccr has been insertionally inactivated, produces only 15 % of the
      monensin yield. Labelling of the coenzyme A pools using [3H]-beta-alanine and
      analysis of intracellular acyl-CoAs in the L1 and C730.1 strains demonstrated
      that loss of ccr led to lower levels of the monensin precursor methymalonyl-CoA,
      relative to coenzyme A. Expression of a heterologous ccr gene from Streptomyces
      collinus fully restored monensin production to the L1 mutant. Using C730.1 and an
      oil-based extended fermentation an exceptionally efficient and comparably intact
      incorporation of ethyl [3,4-13C2]acetoacetate into both the ethylmalonyl-CoA- and
      methylmalonyl-CoA-derived positions of monensin was observed. No labelling of the
      malonyl-CoA-derived positions was observed. The opposite result was observed when
      the incorporation study was carried out with the L1 strain, demonstrating that
      ccr insertional inactivation has led to a reversal of carbon flux from an
      acetoacetyl-CoA intermediate. These results dramatically contrast similar
      analyses of the L1 mutant in glucose-soybean medium which indicate a role in
      providing ethylmalonyl-CoA but not methylmalonyl-CoA, thus causing a change in
      the ratio of monensin A and monensin B analogues, but not the overall monensin
      titre. These results demonstrate that the relative contributions of different
      pathways and enzymes to providing polyketide precursors are thus dependent upon
      the fermentation conditions. Furthermore, the generally accepted pathways for
      providing methylmalonyl-CoA for polyketide production may not be significant for
      the S. cinnamonensis high-titre monensin producer in oil-based extended
      fermentations. An alternative pathway, leading from the fatty acid catabolite
      acetyl-CoA, via the CCR-catalysed reaction is proposed.

PMID- 15470125
TI  - Urease activity of enterohaemorrhagic Escherichia coli depends on a specific one
      base substitution in ureD.
AB  - The authors previously reported that most enterohaemorrhagic Escherichia coli
      (EHEC) strains do not express urease activity, despite having the urease gene.
      This study compared the nucleotide sequences of the urease gene clusters of a
      urease-activity-positive and a urease-activity-negative strain. The results
      showed that in the urease-activity-negative strain, ureD, a gene encoding a
      chaperone protein, had a single base substitution that encoded a premature stop
      codon resulting in a short ORF. The premature stop codon in ureD was commonly
      found in urease-activity-negative EHEC strains, but not in urease-activity
      positive strains. Urease activity was detected after complementing the urease
      activity-negative strain with ureD from the urease-activity-positive strain.
      Furthermore, introduction of the urease gene cluster from the urease-activity
      negative strain into an amber suppressor phenotype Escherichia coli strain,
      DH5alpha, conferred the ability to produce the active urease. These results
      suggest that the lack of urease activity in most EHEC strains is due to a
      premature stop codon in ureD.

PMID- 15470124
TI  - Regulation of exopolysaccharide synthesis in Rhizobium sp. strain TAL1145
      involves an alternative sigma factor gene, rpoH2.
AB  - Exopolysaccharide (EPS) produced by Rhizobium sp. strain TAL1145 has been shown
      to be essential for effective nodulation on Leucaena leucocephala (leucaena).
      This paper reports the isolation and characterization of an alternative sigma
      factor gene, rpoH2, involved in the regulation of EPS synthesis in TAL1145.
      Disruption of this gene in TAL1145 resulted in a Calcofluor-dim mutant RUH102
      that produced approximately 18 % of the amount of EPS made by TAL1145. This
      mutation did not affect the normal growth of RUH102 in free-living state. RUH102
      induced few nitrogen-fixing nodules, resulting in a significant reduction in
      total nitrogen content in leucaena. It was complemented for EPS production and
      nodulation by a 2.0 kb HindIII fragment of TAL1145. Sequence analysis of this
      fragment revealed the rpoH2 ORF of 870 bp that encoded a protein of 32 kDa.
      Expression of the rpoH2 ORF in Escherichia coli also revealed a 32 kDa protein. A
      PCR-constructed clone of 1263 bp, containing the rpoH2 ORF and its upstream
      putative regulatory region, complemented RUH102 for EPS defects. Comparison of
      the RpoH2 sequence to proteins in the databases showed significant similarity to
      RpoH-like sigma factors of other Gram-negative bacteria. By constructing several
      exo : : Tn3Hogus fusions and transferring them to the backgrounds of TAL1145 and
      RUH102, it was demonstrated that RpoH2 positively regulates the transcription of
      some exo genes.

PMID- 15470126
TI  - Mycoplasmas associated with canine infectious respiratory disease.
AB  - Canine infectious respiratory disease (CIRD) is a complex infection that occurs
      worldwide predominantly in kennelled dogs, and several bacterial and viral micro
      organisms have been associated with outbreaks of CIRD. However, few studies have
      comprehensively examined the species of mycoplasma present in healthy dogs and
      those with CIRD. As part of an extensive study investigating the micro-organisms
      involved in CIRD, the species of mycoplasma present throughout the respiratory
      tract of dogs with and without CIRD were determined. Mycoplasmas were cultured
      from tonsillar, tracheal and bronchial lavage samples, and identified to the
      species level by PCR and sequencing. Mycoplasma cynos was demonstrated on the
      ciliated tracheal epithelium by in situ hybridization and was the only mollicute
      found to be associated with CIRD, but only in the lower respiratory tract.
      Isolation of M. cynos was correlated with an increased severity of CIRD, younger
      age and a longer time in the kennel.

PMID- 15470127
TI  - The Mycobacterium tuberculosis Rv1099c gene encodes a GlpX-like class II fructose
      1,6-bisphosphatase.
AB  - There are now abundant data indicating that Mycobacterium tuberculosis uses fatty
      acids as a carbon source in vivo. A key enzyme in gluconeogenesis, missing in the
      original annotation of the M. tuberculosis genome, is fructose 1,6-bisphosphatase
      (FBPase; EC 3.1.3.11). The authors have shown that M. tuberculosis Rv1099c, a
      glpX homologue, can complement Escherichia coli mutants lacking FBPase. The
      protein encoded by Rv1099c was shown to have FBPase activity. Rv1099c was
      expressed at significant levels in M. tuberculosis, and may encode the major
      FBPase of this pathogen.

PMID- 15470128
TI  - Nucleotide sequences and comparison of two large conjugative plasmids from
      different Campylobacter species.
AB  - Two large tetracycline resistance (TcR) plasmids have been completely sequenced,
      the pTet plasmid (45.2 kb) from Campylobacter jejuni strain 81-176 and a plasmid
      pCC31 (44.7 kb) from Campylobacter coli strain CC31 that was isolated from a
      human case of severe gastroenteritis in the UK. Both plasmids are mosaic in
      structure, having homologues of genes found in a variety of different commensal
      and pathogenic bacteria, but nevertheless, showed striking similarities in DNA
      sequence and overall gene organization. Several predicted proteins encoded by
      genes involved in conjugation showed highest homology to proteins found in
      Actinobacillus actinomycetemcomitans, a periodontal pathogen. In addition to
      replication- and conjugation-associated genes, both plasmids carried a tet(O)
      gene encoding tetracycline resistance, a 6 kb ORF encoding a putative methylase
      and a number of genes of unknown function. The pTet plasmid co-exists in C.
      jejuni strain 81-176 with a smaller, previously characterized, non-conjugative
      plasmid pVir that also encodes a type IV secretion system (T4SS) that may affect
      virulence. In contrast, the T4SS encoded by pTet and pCC31 are shown to mediate
      bacterial conjugation between Campylobacter. The possible origin and evolution of
      pCC31 and pTet is discussed.

PMID- 15470129
TI  - The zebrafish nrc mutant reveals a role for the polyphosphoinositide phosphatase
      synaptojanin 1 in cone photoreceptor ribbon anchoring.
AB  - Visual, vestibular, and auditory neurons rely on ribbon synapses for rapid
      continuous release and recycling of synaptic vesicles. Molecular mechanisms
      responsible for the properties of ribbon synapses are mostly unknown. The
      zebrafish vision mutant nrc has unanchored ribbons and abnormal synaptic
      transmission at cone photoreceptor synapses. We used positional cloning to
      identify the nrc mutation as a premature stop codon in the synaptojanin1 (synj1)
      gene. Synaptojanin 1 (Synj1) is undetectable in nrc extracts, and biochemical
      activities associated with it are reduced. Furthermore, morpholinos directed
      against synj1 phenocopy the nrc mutation. Synj1 is a polyphosphoinositide
      phosphatase important at conventional synapses for clathrin-mediated endocytosis
      and actin cytoskeletal rearrangement. In the nrc cone photoreceptor pedicle, not
      only are ribbons unanchored, but synaptic vesicles are reduced in number,
      abnormally distributed, and interspersed within a dense cytoskeletal matrix. Our
      findings reveal a new role for Synj1 and link phosphoinositide metabolism to
      ribbon architecture and function at the cone photoreceptor synapse.

PMID- 15470130
TI  - Survival of adult spiral ganglion neurons requires erbB receptor signaling in the
      inner ear.
AB  - Degeneration of cochlear sensory neurons is an important cause of hearing loss,
      but the mechanisms that maintain the survival of adult cochlear sensory neurons
      are not clearly defined. We now provide evidence implicating the neuregulin (NRG)
      erbB receptor signaling pathway in this process. We found that NRG1 is expressed
      by spiral ganglion neurons (SGNs), whereas erbB2 and erbB3 are expressed by
      supporting cells of the organ of Corti, suggesting that these molecules mediate
      interactions between these cells. Transgenic mice in which erbB signaling in
      adult supporting cells is disrupted by expression of a dominant-negative erbB
      receptor show severe hearing loss and 80% postnatal loss of type-I SGNs without
      concomitant loss of the sensory cells that they contact. Quantitative RT-PCR
      analysis of neurotrophic factor expression shows a specific downregulation in
      expression of neurotrophin-3 (NT3) in the transgenic cochleas before the onset of
      neuronal death. Because NT3 is critical for survival of type I SGNs during
      development, these results suggest that it plays similar roles in the adult.
      Together, the data indicate that adult cochlear supporting cells provide critical
      trophic support to the neurons, that survival of postnatal cochlear sensory
      neurons depends on reciprocal interactions between neurons and supporting cells,
      and that these interactions are mediated by NRG and neurotrophins.

PMID- 15470131
TI  - Failure to consolidate the consolidation theory of learning for sensorimotor
      adaptation tasks.
AB  - An influential idea in human motor learning is that there is a consolidation
      period during which motor memories are transformed from a fragile to a permanent
      state, no longer susceptible to interference from new learning. The evidence
      supporting this idea comes from studies showing that the motor memory of a task
      (A) is lost when an opposing task (B) is experienced soon after, but not if
      sufficient time is allowed to pass (approximately 6 hr). We report results from
      three laboratories challenging this consolidation idea. We used an ABA paradigm
      in the context of a reaching task to assess the influence of experiencing B after
      A on the retention of A. In two experiments using visuomotor rotations, we found
      that B fully interferes with the retention of A even when B is experienced 24 hr
      after A. Contrary to previous reports, in four experiments on learning force
      fields, we also observed full interference between A and B when they are
      separated by 24 hr or even 1 week. This latter result holds for both position
      dependent and velocity-dependent force fields. For both the visuomotor and force
      field tasks, complete interference is still observed when the possible affects of
      anterograde interference are controlled through the use of washout trials. Our
      results fail to support the idea that motor memories become consolidated into a
      protected state. Rather, they are consistent with recent ideas of memory
      formation, which propose that memories can shift between active and inactive
      states.

PMID- 15470132
TI  - The GABAA receptor gamma2 subunit R43Q mutation linked to childhood absence
      epilepsy and febrile seizures causes retention of alpha1beta2gamma2S receptors in
      the endoplasmic reticulum.
AB  - The GABA(A) receptor gamma2 subunit mutation R43Q is an autosomal dominant
      mutation associated with childhood absence epilepsy and febrile seizures.
      Previously, we demonstrated that homozygous alpha1beta3gamma2L(R43Q) receptor
      whole-cell currents had reduced amplitude with unaltered time course, suggesting
      reduced cell surface expression of functional receptors. In human embryonic
      kidney 293-T cells, we demonstrate that both heterozygous and homozygous
      alpha1beta2gamma2S(R43Q) GABA(A) receptor current amplitudes were reduced when
      receptors were assembled from coexpressed alpha1, beta2, and gamma2S subunits and
      from beta2-alpha1 tandem subunits coexpressed with the gamma2L subunit. Using
      fluorescence confocal microscopy, we demonstrated that mutant receptors
      containing enhanced yellow fluorescent protein-tagged gamma2S subunits had
      reduced surface expression and were retained in the endoplasmic reticulum. In
      addition, using biotinylation of surface receptors and immunoblotting, we
      confirmed that alpha1beta2gamma2S(R43Q) receptors had reduced surface expression.
      These results provide evidence that the gamma2S(R43Q) mutation impaired GABA(A)
      receptor function by compromising receptor trafficking and reducing surface
      expression.

PMID- 15470134
TI  - Detection and masking of spoiled food smells by odor maps in the olfactory bulb.
AB  - Two major causes of spoiled food smells such as fatty, fishy off-flavors are
      alkylamines liberated by bacterial actions and aliphatic acids-aldehydes
      generated by lipid oxidation. Using the method of intrinsic signal imaging, we
      mapped alkylamine-responsive glomeruli to a subregion of the aliphatic acid
      responsive and aldehyde-responsive cluster in the odor maps of rat olfactory
      bulb. Extracellular single-unit recordings from mitral-tufted cells in the
      subregion showed that individual cells responded to the alkylamines in addition
      to acids and aldehydes. Responses of mitral-tufted cells tended to last for a
      long period (5-88 sec) even after the cessation of the alkylamine stimulation.
      These results suggest that the subregion is part of the representation of the
      fatty, fishy odor quality. Fennel and clove, spices known to add flavor and mask
      the fatty, fishy odor, activated glomeruli in the surrounding clusters and
      suppressed the alkylamine-induced and acid-aldehyde-induced responses of mitral
      cells, suggesting that the odor masking is mediated, in part, by lateral
      inhibitory connections in the odor maps of the olfactory bulb.

PMID- 15470133
TI  - Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels.
AB  - Acid-sensing ion channels (ASICs), a novel class of ligand-gated cation channels
      activated by protons, are highly expressed in peripheral sensory and central
      neurons. Activation of ASICs may play an important role in physiological
      processes such as nociception, mechanosensation, and learning-memory, and in the
      pathology of neurological conditions such as brain ischemia. Modulation of the
      activities of ASICs is expected to have a significant influence on the roles that
      these channels can play in both physiological and/or pathological processes. Here
      we show that the divalent cation Zn2+, an endogenous trace element, dose
      dependently inhibits ASIC currents in cultured mouse cortical neurons at
      nanomolar concentrations. With ASICs expressed in Chinese hamster ovary cells,
      Zn2+ inhibits currents mediated by homomeric ASIC1a and heteromeric ASIC1a-ASIC2a
      channels, without affecting currents mediated by homomeric ASIC1beta, ASIC2a, or
      ASIC3. Consistent with ASIC1a-specific modulation, high-affinity Zn2+ inhibition
      is absent in neurons from ASIC1a knock-out mice. Current-clamp recordings and
      Ca2+-imaging experiments demonstrated that Zn2+ inhibits acid-induced membrane
      depolarization and the increase of intracellular Ca2+. Mutation of lysine-133 in
      the extracellular domain of the ASIC1a subunit abolishes the high-affinity Zn2+
      inhibition. Our studies suggest that Zn2+ may play an important role in a
      negative feedback system for preventing overexcitation of neurons during normal
      synaptic transmission and ASIC1a-mediated excitotoxicity in pathological
      conditions.

PMID- 15470135
TI  - Regulation of neuronal excitability through pumilio-dependent control of a sodium
      channel gene.
AB  - Dynamic changes in synaptic connectivity and strength, which occur during both
      embryonic development and learning, have the tendency to destabilize neural
      circuits. To overcome this, neurons have developed a diversity of homeostatic
      mechanisms to maintain firing within physiologically defined limits. In this
      study, we show that activity-dependent control of mRNA for a specific voltage
      gated Na+ channel [encoded by paralytic (para)] contributes to the regulation of
      membrane excitability in Drosophila motoneurons. Quantification of para mRNA, by
      real-time reverse-transcription PCR, shows that levels are significantly
      decreased in CNSs in which synaptic excitation is elevated, whereas, conversely,
      they are significantly increased when synaptic vesicle release is blocked.
      Quantification of mRNA encoding the translational repressor pumilio (pum) reveals
      a reciprocal regulation to that seen for para. Pumilio is sufficient to influence
      para mRNA. Thus, para mRNA is significantly elevated in a loss-of-function allele
      of pum (pum(bemused)), whereas expression of a full-length pum transgene is
      sufficient to reduce para mRNA. In the absence of pum, increased synaptic
      excitation fails to reduce para mRNA, showing that Pum is also necessary for
      activity-dependent regulation of para mRNA. Analysis of voltage-gated Na+ current
      (I(Na)) mediated by para in two identified motoneurons (termed aCC and RP2)
      reveals that removal of pum is sufficient to increase one of two separable I(Na)
      components (persistent I(Na)), whereas overexpression of a pum transgene is
      sufficient to suppress both components (transient and persistent). We show,
      through use of anemone toxin (ATX II), that alteration in persistent I(Na) is
      sufficient to regulate membrane excitability in these two motoneurons.

PMID- 15470136
TI  - Histamine H3 receptors inhibit serotonin release in substantia nigra pars
      reticulata.
AB  - The substantia nigra pars reticulata (SNr) plays a key role in basal ganglia
      function. Projections from multiple basal ganglia nuclei converge at the SNr to
      regulate nigrothalamic output. The SNr is also characterized by abundant
      aminergic input, including dopaminergic dendrites and axons containing 5
      hydroxytryptamine (5-HT) or histamine (HA). The functions of HA in the SNr
      include motor control via HA H3 receptors (H3Rs), although the mechanism remains
      far from elucidated. In Parkinson's disease, there is an increase in H3Rs and the
      density of HA-immunoreactive axons in the SN. We explored the role of H3Rs in the
      regulation of 5-HT release in SNr using fast-scan cyclic voltammetry at carbon
      fiber microelectrodes in rat midbrain slices. Immunohistochemistry identified a
      similar distribution for histaminergic and serotonergic processes in the SNr:
      immunoreactive varicosities were observed in the vicinity of dopaminergic
      dendrites. Electrically evoked 5-HT release was dependent on extracellular Ca2+
      and prevented by NaV+-channel blockade. Extracellular 5-HT concentration was
      enhanced by inhibition of uptake transporters for 5-HT but not dopamine.
      Selective H3R agonists (R)-(-)-alpha-methyl-histamine or immepip inhibited evoked
      5-HT release by up to 60%. This inhibition was prevented by the H3R antagonist
      thioperamide but not by the 5-HT1B receptor antagonist isamoltane. H3R inhibition
      of 5-HT release prevailed in the presence of GABA or glutamate receptor
      antagonists (ionotropic and metabotropic), suggesting minimal involvement of GABA
      or glutamate synapses. The potent regulation of 5-HT by H3Rs reported here not
      only elucidates HA function in the SNr but also raises the possibility of novel
      targets for basal ganglia therapies.

PMID- 15470137
TI  - Laminar patterning in the developing neocortex by temporally coordinated
      fibroblast growth factor signaling.
AB  - Laminar organization, a fundamental neural architecture in the CNS, is a
      prominent feature of the neocortex, where the cortical neurons in spatially
      distinct layers are generated from the common progenitors in a temporally
      distinct manner during development. Despite many advances in the characterization
      of the molecular mechanisms of the radial migration of cortical neurons, the way
      in which the early-late temporal sequence of cortical neuron generation is linked
      with the deep-superficial spatial sequence of cell body positioning remains
      obscure. Using in vivo electroporation-mediated gene transfer, we show here that
      the activities mediated by fibroblast growth factor receptors (FGFRs) in cortical
      progenitors are critical for conferring proper migratory properties on nascent
      neuronal progeny. Furthermore, we provide supportive evidence that Pea3 subfamily
      members of Ets (Pea3-Ets) transcription factors mediate the activities of FGFR at
      the mid to late phase of neocortical development. In addition, using FGF18 knock
      out mice, we demonstrate that FGF18 expressed by early-generated cortical neurons
      in the cortical plate is critical for the expression of Pea3-Ets transcription
      factors and that FGF18 is sufficient to induce their expressions. Our results
      thus imply that a feedback mechanism mediated by FGF signaling is involved in
      setting up the proper laminar positioning of cortical neurons; FGF18 derived from
      early-generated cortical neurons acts on the cortical progenitors expressing
      FGFRs and induces the expression of Pea3-Ets transcription factors that, in turn,
      confer proper migratory behaviors on nascent cortical progeny during the mid to
      late stages of neocortical development.

PMID- 15470138
TI  - B-myb and C-myb play required roles in neuronal apoptosis evoked by nerve growth
      factor deprivation and DNA damage.
AB  - Activation of cell cycle elements plays a required role in neuronal apoptosis
      associated with both development and neurodegenerative disorders. We demonstrated
      previously that neuron survival requires gene repression mediated by the cell
      cycle transcription factor E2F (E2 promoter binding factor) and that apoptotic
      stimuli lead to de-repression of E2F-regulated genes and consequent death.
      However, the downstream mediators of such death have been unclear. The
      transcription factors B- and C-myb are E2F-regulated genes that are induced in
      neurons by apoptotic stimuli. Here, we examine the role of B- and C-myb induction
      in neuron death. Antisense and siRNA constructs that effectively block the
      upregulation of B- and C-myb provide substantial protection against death of
      cultured neuronal PC12 cells, sympathetic neurons, and cortical neurons elicited
      by either NGF withdrawal or DNA damage. There is also significant protection from
      death induced by direct E2F-dependent gene de-repression. Our findings thus
      establish required roles for B- and C-myb in neuronal apoptosis.

PMID- 15470139
TI  - Switching mature retinal ganglion cells to a robust growth state in vivo: gene
      expression and synergy with RhoA inactivation.
AB  - The inability of mature CNS neurons to regenerate injured axons has been
      attributed to a loss of inherent growth potential of cells and to inhibitory
      signals associated with myelin and the glial scar. The present study investigated
      two complementary issues: (1) whether mature CNS neurons can be stimulated to
      alter their gene expression profile and switch into a strong growth state; and
      (2) whether inactivating RhoA, a convergence point for multiple inhibitory
      signals, is sufficient to produce strong regeneration even without activating the
      growth state of neurons. In the mature rat, retinal ganglion cells (RGCs)
      normally fail to regenerate axons through the injured optic nerve but can be
      stimulated to do so by activating macrophages in the eye (e.g., by lens injury).
      To investigate underlying changes in gene expression, we retrogradely labeled
      RGCs with a fluorescent dye, performed optic nerve surgery with or without lens
      injury, and 4 d later, dissociated retinas, isolated RGCs by fluorescence
      activated cell sorting, and examined their profiles of gene expression using
      microarrays. To investigate the effects of inactivating RhoA, we transfected RGCs
      with adeno-associated viruses carrying a gene for C3 ribosyltransferase. Our
      results show that, with appropriate stimulation, mature CNS neurons can undergo
      dramatic changes in gene expression comparable with those seen in regenerating
      neurons of the PNS, and that RhoA inactivation by itself results in moderate
      regeneration, and strongly potentiates axon regeneration through the mature optic
      nerve when the growth state of neurons is activated.

PMID- 15470140
TI  - Neuropeptide Y inhibits hypocretin/orexin neurons by multiple presynaptic and
      postsynaptic mechanisms: tonic depression of the hypothalamic arousal system.
AB  - Neurons that release neuropeptide Y (NPY) have important effects on hypothalamic
      homeostatic regulation, including energy homeostasis, and innervate hypocretin
      neurons. Using whole-cell patch-clamp recording, we explored NPY actions on
      hypocretin cells identified by selective green fluorescent protein expression in
      mouse hypothalamic slices. NPY reduced spike frequency and hyperpolarized the
      membrane potential of hypocretin neurons. The NPY hyperpolarizing action
      persisted in tetrodotoxin (TTX), was mimicked by Y1 receptor-selective agonists
      [Pro34]-NPY and [D-Arg25]-NPY, and was abolished by the Y1-specific antagonist
      BIBP3226 [(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine-amide],
      consistent with a direct activation of postsynaptic Y1 receptors. NPY induced a
      current that was dependent on extracellular potassium, reversed near the
      potassium equilibrium potential, showed inward rectification, was blocked by
      extracellular barium, and was abolished by GDP-betaS in the recording pipette,
      consistent with a G-protein-activated inwardly rectifying K+ (GIRK) current.
      [Pro34]-NPY evoked, and BIBP3226 blocked, the activation of the GIRK-type
      current, indicating mediation by a Y1 receptor. NPY attenuated voltage-dependent
      calcium currents mainly via a Y1 receptor subtype. BIBP3226 increased spontaneous
      spike frequency, suggesting an ongoing Y1 receptor-mediated NPY inhibition. In
      TTX, miniature EPSCs were reduced in frequency but not amplitude by NPY, NPY13
      36, and [D-Trp32]-NPY, but not by [Pro34]-NPY, suggesting the presynaptic
      inhibition was mediated by a Y2/Y5 receptor. NPY had little effect on GABA
      mediated miniature IPSCs but depressed spontaneous IPSCs. Together, these data
      support the view that NPY reduces the activity of hypocretin neurons by multiple
      presynaptic and postsynaptic mechanisms and suggest NPY axons innervating
      hypocretin neurons may tonically attenuate hypocretin-regulated arousal.

PMID- 15470141
TI  - Ral and phospholipase D2-dependent pathway for constitutive metabotropic
      glutamate receptor endocytosis.
AB  - G-protein-coupled receptors play a central role in the regulation of neuronal
      cell communication. Class 1 metabotropic glutamate receptors (mGluRs) mGluR1a and
      mGluR5a, which are coupled with the hydrolysis of phosphoinositides, are
      essential for modulating excitatory neurotransmission at glutamatergic synapses.
      These receptors are constitutively internalized in heterologous cell cultures,
      neuronal cultures, and intact neuronal tissues. We show here that the small GTP
      binding protein Ral, its guanine nucleotide exchange factor RalGDS (Ral GDP
      dissociation stimulator), and phospholipase D2 (PLD2) are constitutively
      associated with class 1 mGluRs and regulate constitutive mGluR endocytosis.
      Moreover, both Ral and PLD2 are colocalized with mGluRs in endocytic vesicles in
      both human embryonic kidney 293 (HEK 293) cells and neurons. Ral and PLD2
      activity is required for the internalization of class 1 mGluRs but is not
      required for the internalization of the beta2-adrenergic receptor. Constitutive
      class 1 mGluR internalization is not dependent on the downstream Ral effector
      proteins Ral-binding protein 1 and PLD1 or either ADP-ribosylation factors ARF1
      or ARF6. The treatment of HEK 293 cells and neurons with small interfering RNA
      both downregulates PLD2 expression and blocks mGluR1a and mGluR5a endocytosis.
      The constitutive internalization of mGluR1a and mGluR5a is also attenuated by the
      treatment of cells with 1-butanol to prevent PLD2-mediated phosphatidic acid
      formation. We propose that the formation of a mGluR-scaffolded RalGDS/Ral/PLD2
      protein complex provides a novel alternative mechanism to beta-arrestins for the
      constitutive endocytosis of class 1 mGluRs.

PMID- 15470143
TI  - Molecular, topographic, and functional organization of the cerebellar cortex: a
      study with combined aldolase C and olivocerebellar labeling.
AB  - Aldolase C (zebrin) expression in Purkinje cells reveals stripe-shaped
      compartments in the cerebellar cortex. However, it is not clear how these
      compartments are related to cerebellar functional localization. Therefore, we
      identified olivocerebellar projections to aldolase C compartments by labeling
      climbing fibers with biotinylated dextran injected into various small areas
      within the inferior olive in rats. Specific rostral and caudal aldolase C
      compartments were linked in an orderly manner by common olivocerebellar
      projection across the rostrocaudal boundary on lobule VIc-crus Ib. Based on the
      localization of the olivary origins of projection to similar compartments, the
      compartments and olivocerebellar projections could be sorted into five groups:
      group I, positive compartments extending from the posterior lobe to the anterior
      lobe innervated by the principal olive and some neighboring areas; group II,
      positive compartments localized within the posterior lobe innervated by several
      medial subnuclei; group III, vermal and central negative compartments innervated
      by the centrocaudal medial accessory olive; group IV, negative and lightly
      positive compartments in the hemisphere and the rostral and caudal pars
      intermedia innervated by the dorsal accessory olive and some neighboring areas;
      group V, the flocculus and nodulus. The olivocerebellar topography within each
      group was simple and suggests an "orientation axis" within the concerned parts of
      the inferior olive. Furthermore, parts of the inferior olive in each group
      receive specific afferent inputs, indicating a close relationship between
      aldolase C compartments and functional localization. Thus, the five-group scheme
      we propose here may integrate the molecular, topographic, and functional
      organization of the cerebellum.

PMID- 15470142
TI  - Characterization of the c-Jun N-terminal kinase-BimEL signaling pathway in
      neuronal apoptosis.
AB  - The c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in
      mediating apoptosis in the nervous system; however, the mechanisms by which JNK
      triggers neuronal apoptosis remain incompletely understood. Recent studies
      suggest that in addition to inducing transcription of pro-apoptotic genes, JNK
      also directly activates the cell death machinery. Here, we report that JNK
      catalyzed the phosphorylation of the BH3-only protein Bcl-2 interacting mediator
      of cell death (BimEL) at serine 65, both in vitro and in vivo. The JNK-induced
      phosphorylation of BimEL at serine 65 promoted the apoptotic effect of BimEL in
      primary cerebellar granule neurons. We also characterized the role of the JNK
      BimEL signaling pathway in apoptosis that was triggered by overexpression of the
      p75 neurotrophin receptor (p75NTR). We found that activation of p75NTR induced
      the JNK-dependent phosphorylation of endogenous BimEL at serine 65 in cells. The
      genetic knockdown of BimEL by RNA interference or the expression of a dominant
      interfering form of BimEL significantly impaired the ability of activated p75NTR
      to induce apoptosis. Together, these results suggest that JNK-induced
      phosphorylation of BimEL at serine 65 mediates p75NTR-induced apoptosis. Our
      findings define a novel mechanism by which a death-receptor pathway directly
      activates the mitochondrial apoptotic machinery.

PMID- 15470144
TI  - Altered social behavior in pituitary adenylate cyclase-activating polypeptide
      type I receptor-deficient mice.
AB  - The olfactory bulb plays a critical role in odor discrimination and in processing
      olfactory cues controlling social behavior in mammals. Given that the pituitary
      adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1) is highly
      expressed in the olfactory bulb, we examined its role in regulating olfaction and
      social investigation. We found that olfactory detection of nonsocial stimuli was
      similar in PAC1-deficient mice and wild-type (WT) littermates. In contrast, PAC1
      deficient mice displayed markedly abnormal social behaviors. PAC1-deficient mice
      exhibited a faster decrease in social investigation after repeated exposure to
      social cues or ovariectomized female urine compared with WT mice. Moreover, PAC1
      deficient females exhibited delayed affiliative behavior when housed with novel
      males, and PAC1-deficient males displayed excessive sexual mounting toward both
      females and males as well as reduced aggression and increased licking and
      grooming toward intruder males. In aggregate, these results uncover PAC1
      signaling as an important factor in the development and/or functioning of neural
      pathways associated with pheromone processing and the regulation of social
      interactions in mice. In turn, these studies raise the potential clinical
      relevance of PACAP signaling dysfunctions in neuropsychiatric disorders
      characterized by social reciprocity impairments such as autism spectrum
      disorders.

PMID- 15470145
TI  - Developmentally regulated switch in alternatively spliced SNAP-25 isoforms alters
      facilitation of synaptic transmission.
AB  - Although the basic molecular components that promote regulated neurotransmitter
      release are well established, the contribution of these proteins as regulators of
      the plasticity of neurotransmission and refinement of synaptic connectivity
      during development is elaborated less fully. For example, during the period of
      synaptic growth and maturation in brain, the expression of synaptosomal protein
      25 kDa (SNAP-25), a neuronal t-SNARE (soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor) essential for action potential-dependent
      neuroexocytosis, is altered through alternative splicing of pre-mRNA transcripts.
      We addressed the role of the two splice-variant isoforms of SNAP-25 with a
      targeted mouse mutation that impairs the shift from SNAP-25a to SNAP-25b. Most of
      these mutant mice die between 3 and 5 weeks of age, which coincides with the time
      when SNAP-25b expression normally reaches mature levels in brain and synapse
      formation is essentially completed. The altered expression of these SNAP-25
      isoforms influences short-term synaptic function by affecting facilitation but
      not the initial probability of release. This suggests that mechanisms controlling
      alternative splicing between SNAP-25 isoforms contribute to a molecular switch
      important for survival that helps to guide the transition from immature to mature
      synaptic connections, as well as synapse regrowth and remodeling after neural
      injury.

PMID- 15470146
TI  - Distribution and injury-induced plasticity of cadherins in relationship to
      identified synaptic circuitry in adult rat spinal cord.
AB  - Cadherins are synaptically enriched cell adhesion and signaling molecules. In
      brain, they function in axon targeting and synaptic plasticity. In adult spinal
      cord, their localization, synaptic affiliation, and role in injury-related
      plasticity are mostly unexplored. Here, we demonstrate in adult rat dorsal horn
      that E- and N-cadherin display unique patterns of localization to functionally
      distinct types of synapses of intrinsic and primary afferent origin. Within the
      nociceptive afferent pathway to lamina II, nonpeptidergic C-fiber synapses in the
      deeper half of lamina II (IIi) contain E-cadherin but mostly lack N-cadherin,
      whereas the majority of the peptidergic C-fiber synapses in the outer half of
      lamina II (IIo) contain N-cadherin but lack E-cadherin. Approximately one-half of
      the Abeta-fiber terminations in lamina III contain N-cadherin; none contain E
      cadherin. Strikingly, the distribution and levels of these cadherins are
      differentially affected by sciatic nerve axotomy, a model of neuropathic pain in
      which degenerative and regenerative structural plasticity has been implicated.
      Within the first 7 d after axotomy, E-cadherin is rapidly and completely lost
      from the dorsal horn synapses with which it is affiliated, whereas N-cadherin
      localization and levels are unchanged; such patterns persist through 28 d
      postlesion. The loss of E-cadherin thus occurs before the onset of mechanical
      hyperalgesia (approximately 10-21 d postlesion), as reported previously.
      Together, the synaptic specificity displayed by these cadherins, coupled with
      their differential response to injury, suggests that they may proactively
      contribute to the maintenance of some, and incipient dismantling of other,
      synaptic circuits in response to nerve injury. Speculatively, such changes may
      ultimately contribute to subsequently emerging abnormalities in pain perception.

PMID- 15470147
TI  - Calcium-activated potassium channels are selectively coupled to P/Q-type calcium
      channels in cerebellar Purkinje neurons.
AB  - Cerebellar Purkinje neurons fire spontaneously in the absence of synaptic
      transmission. P/Q-type voltage-gated calcium channels and calcium-activated
      potassium channels are required for normal spontaneous activity. Blocking P/Q
      type calcium channels paradoxically mimics the effects of blocking calcium
      activated potassium channels. Thus, an important function of the P/Q-type calcium
      channels is to provide calcium for activation of calcium-activated potassium
      channels. Purkinje neurons express several classes of voltage-gated calcium
      channels, and the P/Q- and T-type channels make comparable contributions to total
      calcium entry after an action potential. Here we demonstrate that calcium
      activated potassium channels are activated exclusively by calcium entering
      through P/Q-type voltage-gated calcium channels. This selective coupling is
      maintained even when calcium flux through voltage-gated channels is increased by
      increasing the extracellular calcium concentration. Small decreases in P/Q
      current density are likely to alter spontaneous activity of Purkinje neurons via
      decreased recruitment of calcium-activated potassium channels. In both human and
      murine animal models, mutations that decrease P/Q current density in Purkinje
      neurons also cause cerebellar ataxia. Alterations in the spontaneous activity of
      Purkinje neurons may be an important contributing factor to the ataxia in these
      subjects.

PMID- 15470148
TI  - The role of cAMP response element-binding protein in Drosophila long-term memory.
AB  - In Drosophila, the transcription factor cAMP response element-binding protein 2
      (dCREB2) has been reported to modulate the formation of long-term olfactory
      memory (LTM). Overexpression of a repressor isoform of CREB (dCREB2-b) under the
      control of a heat-shock promoter was reported to block LTM, whereas
      overexpression of an activator isoform (dCREB2-a) was reported to enhance LTM. A
      ratiometric model based on these results predicts that the balance of functional
      dCREB2-a and dCREB2-b provides a switch for memories to remain labile or to
      become enduring. We show here that the dCREB2-a transgene originally reported to
      enhance LTM carries a mutation that produces a translational reading-frame shift
      with the consequent formation of a stop codon at predicted amino acid position
      79. Overexpression of this mutant dCREB2-a transgene or a corrected dCREB2-a
      transgene failed to show any enhancement of LTM. Overexpression of the dCREB2-b
      repressor transgene, in contrast, produced the anticipated block in LTM
      formation. We discuss the implications of these findings and propose an
      alternative model for the role of dCREB in Drosophila LTM.

PMID- 15470149
TI  - Coregulation of glutamate uptake and long-term sensitization in Aplysia.
AB  - In Aplysia, long-term facilitation (LTF) at sensorimotor synapses of the pleural
      pedal ganglia is mediated by an increase in the release of a neurotransmitter,
      which appears to be glutamate. Glutamate uptake also is increased in sensory
      neurons 24 hr after the induction of long-term sensitization (Levenson et al.,
      2000b). The present study investigated whether the same signaling pathways were
      involved in the long-term increase in glutamate uptake as in the induction of
      LTF. Thus, roles for cAMP, PKA (cAMP-dependent protein kinase), MAPK (mitogen
      activated protein kinase), and tyrosine kinase in the regulation of glutamate
      uptake were tested. We found that 5-HT increased cAMP and activated PKA in
      sensory neurons. Exposure of pleural-pedal ganglia to analogs of cAMP or
      forskolin increased glutamate uptake 24 hr after treatments. Inhibitors of PKA
      (KT5720), MAPK (U0126 and PD98059), and tyrosine kinase (genistein) blocked the
      long-term increase in glutamate uptake produced by 5-HT. In addition, bpV, a
      tyrosine phosphatase inhibitor, facilitated the ability of subthreshold levels of
      5-HT to increase glutamate uptake. Inhibition of PKC, which is not involved in
      LTF, had no effect on the long-term increase in glutamate uptake produced by 5
      HT. Furthermore, activation of PKC by phorbol-12,13-dibutyrate did not produce
      long-term changes in glutamate uptake. The results demonstrate that the same
      constellation of second messengers and kinases is involved in the long-term
      regulation of both glutamate release and glutamate uptake. These similarities in
      signaling pathways suggest that regulation of glutamate release and uptake during
      formation of long-term memory are coordinated through coregulation of these two
      processes.

PMID- 15470150
TI  - A new platform to study the molecular mechanisms of exocytosis.
AB  - The exocytotic process in neurons and neuroendocrine cells consists of a sequence
      of reactions between well defined proteins. In the present study, we have created
      for the first time a comprehensive kinetic model that demonstrates the dynamics
      of interactions between key synaptic proteins that are associated with
      exocytosis. The interactions between the synaptic proteins were transformed into
      differential rate equations that, after their integration over time,
      reconstructed the experimental signal. The model can perfectly reconstruct the
      kinetics of exocytosis, the calcium-dependent priming and fusion processes, and
      the effects of genetic manipulation of synaptic proteins. The model suggests that
      fusion occurs from two parallel pathways and assigns precise, non-identical
      synaptic protein complexes to the two pathways. In addition, it provides a unique
      opportunity to study the dynamics of intermediate protein complexes during the
      fusion process, a possibility that is hidden in most experimental systems. We
      thus developed a novel approach that allows detailed characterization of the
      temporal relationship between synaptic protein complexes. This model provides an
      excellent platform for prediction and quantification of the effects of protein
      manipulations on exocytosis and opens new avenues for experimental investigation
      of exocytosis.

PMID- 15470151
TI  - Selection for cognitive control: a functional magnetic resonance imaging study on
      the selection of task-relevant information.
AB  - The complex environment we live in makes it necessary to distinguish relevant
      from irrelevant information constantly and reliably. The aim of the present study
      was to investigate the neural substrate underlying the selection of task-relevant
      information. We devised a new paradigm in which participants had to switch
      between two different tasks that were instructed by task cues. The task cues had
      a relevant and an irrelevant cue dimension. In congruent trials, both cue
      dimensions indicated the same task; in incongruent trials, they indicated
      different tasks; and in neutral trials, only the relevant dimension indicated a
      task. By comparing trials in which both cue dimensions were informative
      (congruent and incongruent trials) with trials in which only the relevant
      dimension was informative (neutral trials), we were able to show that the lateral
      prefrontal cortex and a region in the intraparietal sulcus are involved in the
      selection of task-relevant information. Furthermore, the present paradigm allows
      the influence of the selected task and stimulus dimension to be investigated. No
      significant influence was found in the prefrontal cortex, indicating that this
      region serves a very abstract role in the selection of task-relevant information.

PMID- 15470152
TI  - Recovery from polyglutamine-induced neurodegeneration in conditional SCA1
      transgenic mice.
AB  - Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant, polyglutamine
      induced neurodegenerative disorder that results in loss of motor coordination
      caused primarily by a disruption of cerebellar Purkinje cell function. In this
      study, we developed a conditional SCA1 mouse model to examine whether stopping
      expression of mutant ataxin-1 alters the disease phenotype. After cessation of
      SCA1[82Q] transgene expression, mutant ataxin-1, including that in nuclear
      inclusions, was cleared rapidly from Purkinje cells. At an early stage of
      disease, Purkinje cell pathology and motor dysfunction were completely
      reversible. After halting SCA1 expression at later stages of disease, only a
      partial recovery was seen. Interestingly, restoration of the ability to perform a
      complex motor task, the accelerating Rotarod, correlated with localization of
      mGluR1alpha to the Purkinje cell-parallel fiber synapse. These results show that
      the progression of SCA1 pathogenesis is dependent on the continuous expression of
      mutant ataxin-1. Of note, even at a late stage of disease, Purkinje cells retain
      at least some ability to repair the damage caused by mutant ataxin-1.

PMID- 15470153
TI  - SynGAP regulates spine formation.
AB  - SynGAP is a brain-specific ras GTPase-activating protein that is an abundant
      component of the signaling complex associated with the NMDA-type glutamate
      receptor. We generated mutant mice lacking synGAP to study its physiological
      role. Homozygous mutant mice die in the first few days after birth; however,
      neurons from mutant embryos can be maintained in culture. Here, we report that
      spine and synapse formation are accelerated in cultured mutant neurons, and the
      spines of mature mutant neurons are significantly larger than those of wild type.
      Clusters of PSD-95 and subunits of AMPA-type and NMDA-type glutamate receptors
      accumulate in spines of mutant neurons by day 10 in vitro, whereas in wild-type
      neurons they are still mostly located in dendritic shafts. The frequency and
      amplitude of miniature EPSCs are larger in mutant neurons at day 10 in vitro,
      confirming that they have more functional synapses. At day 21 in vitro, the
      spines of mutant neurons remain significantly larger than those of wild type. The
      mutant phenotype at day 10 in vitro can be rescued by introduction of recombinant
      wild-type synGAP on day 9. In contrast, introduction of mutant synGAP with a
      mutated GAP domain or lacking the terminal domain that binds to PSD-95 does not
      rescue the mutant phenotype, indicating that both domains play a role in control
      of spine formation. Thus, the GAP activity of synGAP and its association with PSD
      95 are important for normal regulation of spine and synapse formation in
      hippocampal neurons.

PMID- 15470154
TI  - Timing and balance of inhibition enhance the effect of long-term potentiation on
      cell firing.
AB  - The role of a neuron in neural processing is ultimately determined by whether or
      not it fires an action potential in a given context. Studies on synaptic
      plasticity have focused primarily on changes in EPSPs, and not on whether
      plasticity translates into changes in firing. However, this issue has been
      addressed by examining EPSP-spike (E-S) potentiation, which enhances the ability
      of an EPSP of a fixed slope to elicit spikes after long-term potentiation (LTP).
      Although LTP is thought to underlie learning and memory, E-S potentiation could
      play an equally important role by potentiating the neuronal input-output
      function. Here, we used a combined experimental and theoretical approach to
      examine both the mechanisms underlying E-S potentiation as well as the role of
      inhibition in shaping the input-output function of neurons. Whereas previous
      studies examined tetanus-LTP, in which inhibitory synapses may have undergone
      plasticity, here we examined pairing-induced associative LTP. We determined that
      although intact inhibition was necessary for pairing-induced E-S potentiation,
      inhibitory plasticity was not. We further established using computer simulations
      that a primary mechanism of E-S potentiation was a change in the relative
      recruitment and latency of inhibitory neurons. Although these studies do not
      exclude the presence of additional mechanisms of E-S potentiation that may be
      engaged depending on the induction protocol, they do establish that under intact
      pharmacology, LTP of the Schaffer collateral to CA1 pyramidal neuron synapses
      will produce E-S potentiation as a result of changes in the balance and timing of
      excitation and inhibition.

PMID- 15470155
TI  - Switching of NMDA receptor 2A and 2B subunits at thalamic and cortical synapses
      during early postnatal development.
AB  - Switching of the NMDA receptor 2A (NR2A) and NR2B subunits at NMDA receptors is
      thought to underlie the functional changes that occur in NMDA receptor properties
      during the developmental epoch when neural plasticity is most pronounced. The
      cellular expression of NR2A and NR2B and the NR2 synaptic binding protein
      postsynaptic density-95 (PSD-95) was examined in the mouse somatosensory cortex
      and thalamus from postnatal day 2 (P2) to P15 using reverse transcription-PCR, in
      situ hybridization histochemistry, and immunocytochemistry. The localization of
      NR2A and NR2B subunits and PSD-95 was then studied at synapses in layer IV of
      somatosensory cortex and in the ventral posterior nucleus of the thalamus using
      high-resolution immunoelectron microscopy. At both cortical and thalamic
      synapses, a quantitative switch in the dominant synaptic subunit from NR2B to
      NR2A was accompanied by a similar change in the cellular expression of NR2A but
      not of NR2B. Synaptic PSD-95 developed independently, although both NR2A and NR2B
      colocalized with PSD-95. Displacement of NR2B subunits from synapses was not
      accompanied by an increase in an extrasynaptic pool of this subunit. Thus, the
      switch in synaptic NR2 subunit predominance does not occur by changes in
      expression or displacement from synapses and may reflect the formation of new
      synapses from which NR2B is lacking.

PMID- 15470156
TI  - Mechanisms of fast ripples in the hippocampus.
AB  - Hippocampal fast ripples (FRs) have been associated with seizure onset in both
      human and experimental epilepsy. To characterize the mechanisms underlying FR
      oscillations (200-600 Hz), we studied activity of single neurons and neuronal
      networks in rat hippocampal slices in vitro. The correlation between the action
      potentials of bursting pyramidal cells and local field potential oscillations
      suggests that synchronous onset of action potential bursts and similar intrinsic
      firing patterns among local neurons are both necessary conditions for FR
      oscillations. Increasing the fidelity of individual pyramidal cell spike train
      timing by blocking accommodation dramatically increased FR amplitude, whereas
      blockade of potassium conductances decreased the fidelity of action potential
      timing in individual pyramidal cell action potential bursts and decreased FR
      amplitude. Blockade of ionotropic glutamate receptors desynchronized onset of
      action potential bursts in individual pyramidal cells and abolished fast ripples.
      Thus, synchronous burst onset mediated by recurrent excitatory synaptic
      transmission and similar intrinsic spike timing mechanisms in neighboring
      pyramidal cells are necessary conditions for FR oscillations within the
      hippocampal network.

PMID- 15470157
TI  - Robustness of multiplicative processes in auditory spatial tuning.
AB  - Auditory space-specific neurons in the owl's inferior colliculus selectively
      respond to the direction of sound propagation, which is defined by combinations
      of interaural time (ITD) and level (ILD) differences. Mathematical analyses show
      that the amplitude of postsynaptic potentials in these neurons is a product of
      two components that vary with either ITD or ILD. Temporal correlation in the fine
      structure of signals between the ears is essential for detection of ITD. By
      varying the degree of binaural correlation, we could accurately change the
      amplitude of the ITD component of postsynaptic potentials in the space-specific
      neurons. Multiplication worked for the entire range of postsynaptic potentials
      created by manipulation of ITD.

PMID- 15470158
TI  - Reducing the uncertainty: gating of peripheral inputs by zona incerta.
AB  - Sensory inputs are relayed to the neocortex by "first-order" thalamic nuclei, the
      responses of which are determined by ascending inputs from peripheral receptors.
      In contrast, "higher-order" thalamic nuclei respond poorly to peripheral inputs,
      and their responses are thought to be determined by descending cortical inputs.
      We tested this hypothesis by recording from neurons in the higher-order
      somatosensory posterior medial (POm) nucleus of narcotized rats. As reported
      previously, POm neurons responded to whisker stimuli with long-latency (median,
      27 msec) and low-magnitude responses, consistent with cortically driven
      responses. However, when we suppressed inhibitory inputs from the subthalamic
      nucleus zona incerta (ZI), POm responses were of significantly higher magnitude
      and shorter latency, with many POm neurons responding at latencies consistent
      with ascending driving inputs from trigeminal nuclei. Our data suggest that POm
      comprises two neuronal populations: one population is driven by both peripheral
      and cortical inputs, and the second population responds only to cortical inputs.
      These findings demonstrate that ZI gates peripheral inputs to POm, enabling it to
      function both as a first-order and higher-order nucleus. Because ZI innervates
      all higher-order nuclei, this gating mechanism may exert similar regulation of
      thalamic processing in other sensory systems.

PMID- 15470159
TI  - Time-dependent inhibition and tetrahydrobiopterin depletion of endothelial nitric
      oxide synthase caused by cigarettes.
AB  - Smoking causes a dysfunction in endothelial nitric-oxide synthase (eNOS), which
      is ameliorated, in part, by administration of tetrahydrobiopterin (BH(4)). The
      exact mechanism by which the nitric oxide deficit occurs is unknown. We have
      previously shown that aqueous extracts of chemicals in cigarettes (CE) cause the
      suicide inactivation of neuronal NO synthase (nNOS) by interacting at the
      substrate-binding site. In the current study, we have found that CE directly
      inactivates eNOS by a process that is not affected by the natural substrate l
      arginine and is distinct from the mechanism of inactivation of nNOS. We
      discovered that CE causes a time-, concentration-, and NADPH-dependent
      inactivation of eNOS in an in vitro system containing the purified enzyme,
      indicating a metabolic component to the inactivation. The CE-treated eNOS but not
      nNOS was nearly fully reactivated upon incubation with excess BH(4), suggesting
      that BH(4) depletion is a potential mechanism of inactivation. Moreover, in the
      presence of CE, eNOS catalyzed the oxidation of BH(4) to dihydrobiopterin and
      biopterin by a process attenuated by high concentrations of superoxide dismutase
      but not catalase. We speculate that a redox active component in CE, perhaps a
      quinone compound, causes oxidative uncoupling of eNOS to form superoxide, which
      in turn oxidizes BH(4). The discovery of a direct inactivation of eNOS by a
      compound(s) present in tobacco provides a basis not only for further study of the
      mechanisms responsible for the biological effects of tobacco but also a search
      for a potentially novel inactivator of eNOS.

PMID- 15470160
TI  - Trans-3'-hydroxycotinine O- and N-glucuronidations in human liver microsomes.
AB  - Trans-3'-hydroxycotinine is a major metabolite of nicotine in humans and is
      mainly excreted as O-glucuronide in smoker's urine. Incubation of human liver
      microsomes with UDP-glucuronic acid produces not only trans-3'-hydroxycotinine O
      glucuronide but also N-glucuronide. The formation of N-glucuronide exceeds the
      formation of O-glucuronide in most human liver microsomes, although N-glucuronide
      has never been detected in human urine. Trans-3'-hydroxycotinine N
      glucuronidation in human liver microsomes was significantly correlated with
      nicotine and cotinine N-glucuronidations, which are catalyzed mainly by UDP
      glucuronosyltransferase (UGT)1A4 and was inhibited by imipramine and nicotine,
      which are substrates of UGT1A4. Recombinant UGT1A4 exhibited substantial trans-3'
      hydroxycotinine N-glucuronosyltransferase activity. These results suggest that
      trans-3'-hydroxycotinine N-glucuronidation in human liver microsomes would be
      mainly catalyzed by UGT1A4. In the present study, trans-3'-hydroxycotinine O
      glucuronidation in human liver microsomes was thoroughly characterized, since
      trans-3'-hydroxycotinine O-glucuronide is one of the major metabolites of
      nicotine. The kinetics were fitted to the Michaelis-Menten equation with a K(m)
      of 10.0 +/- 0.8 mM and a V(max) of 85.8 +/- 3.8 pmol/min/mg. Among 11 recombinant
      human UGT isoforms expressed in baculovirus-infected insect cells, UGT2B7
      exhibited the highest trans-3'-hydroxycotinine O-glucuronosyltransferase activity
      (1.1 pmol/min/mg) followed by UGT1A9 (0.3 pmol/min/mg), UGT2B15 (0.2
      pmol/min/mg), and UGT2B4 (0.2 pmol/min/mg) at a substrate concentration of 1 mM.
      Trans-3'-hydroxycotinine O-glucuronosyltransferase activity by recombinant UGT2B7
      increased with an increase in the substrate concentration up to 16 mM (10.5
      pmol/min/mg). The kinetics by recombinant UGT1A9 were fitted to the Michaelis
      Menten equation with K(m) = 1.6 +/- 0.1 mM and V(max) = 0.69 +/- 0.02 pmol/min/mg
      of protein. Trans-3'-hydroxycotinine O-glucuronosyltransferase activities in 13
      human liver microsomes ranged from 2.4 to 12.6 pmol/min/mg and were significantly
      correlated with valproic acid glucuronidation (r = 0.716, p < 0.01), which is
      catalyzed by UGT2B7, UGT1A6, and UGT1A9. Trans-3'-hydroxycotinine O
      glucuronosyltransferase activity in human liver microsomes was inhibited by
      imipramine (a substrate of UGT1A4, IC(50) = 55 microM), androstanediol (a
      substrate of UGT2B15, IC(50) = 169 microM), and propofol (a substrate of UGT1A9,
      IC(50) = 296 microM). Interestingly, imipramine (IC(50) = 45 microM),
      androstanediol (IC(50) = 21 microM), and propofol (IC(50) = 41 microM) also
      inhibited trans-3'-hydroxycotinine O-glucuronosyltransferase activity by
      recombinant UGT2B7. These findings suggested that trans-3'-hydroxycotinine O
      glucuronidation in human liver microsomes is catalyzed by mainly UGT2B7 and, to a
      minor extent, by UGT1A9.

PMID- 15470161
TI  - Identification of the UDP-glucuronosyltransferase isoforms involved in
      mycophenolic acid phase II metabolism.
AB  - Mycophenolic acid (MPA), the active metabolite of the immunosuppressant
      mycophenolate mofetil is primarily metabolized by glucuronidation. The nature of
      UDP-glucuronosyltransferases (UGTs) involved in this pathway is still debated.
      The present study aimed at identifying unambiguously the UGT isoforms involved in
      the production of MPA-phenyl-glucuronide (MPAG) and MPA-acylglucuronide (AcMPAG).
      A liquid chromatography-tandem mass spectrometry method allowing the
      identification and determination of the metabolites of mycophenolic acid was
      developed. The metabolites were characterized in urine and plasma samples from
      renal transplant patients under mycophenolate mofetil therapy and in vitro after
      incubation of mycophenolic acid with human liver (HLM), kidney (HKM), or
      intestinal microsomes (HIM). The UGT isoforms involved in MPAG or AcMPAG
      production were investigated using induced rat liver microsomes, heterologously
      expressed UGT (Supersomes), and chemical-selective inhibition of HLM, HKM, and
      HIM. The three microsomal preparations produced MPAG, AcMPAG, and two
      mycophenolate glucosides. Among the 10 UGT isoforms tested, UGT 1A9 was the most
      efficient for MPAG synthesis with a K(m) of 0.16 mM, close to that observed for
      HLM (0.18 mM). According to the chemical inhibition experiments, UGT 1A9 is
      apparently responsible for 55%, 75%, and 50% of MPAG production by the liver,
      kidney, and intestinal mucosa, respectively. Although UGT 2B7 was the only
      isoform producing AcMPAG in a significant amount, the selective inhibitor
      azidothymidine only moderately reduced this production (approximately -25%). In
      conclusion, UGT 1A9 and 2B7 were clearly identified as the main UGT isoforms
      involved in mycophenolic acid glucuronidation, presumably due to their high
      hepatic and renal expression.

PMID- 15470162
TI  - The effect of perioperative beta-blockers on patients undergoing noncardiac
      surgery - is the answer in?

PMID- 15470163
TI  - Anesthesia-related medication error: time to take action.

PMID- 15470164
TI  - Perioperative use of beta-blockers remains low: experience of a single Canadian
      tertiary institution.
AB  - BACKGROUND: Perioperative beta-blockade appears to reduce morbidity and mortality
      in non-cardiac surgery, and is recommended by published guidelines. This study
      explores the frequency of perioperative beta-blockade and identifies factors
      limiting its use. METHODS: We conducted a prospective analysis of consecutive
      patients seen by anesthesiologists before major non-cardiac surgery in a single
      month. Because not all patients undergoing major surgery were seen preoperatively
      by anesthesiologists, we also performed a retrospective analysis of patients who
      recently underwent such surgery. Data were collected on demographic information,
      cardiovascular risk factors, beta-blocker use, and perceived
      contraindications/barriers to beta-blocker use, using a validated instrument.
      RESULTS: The prospective phase studied 222 patients preoperatively, of whom 96
      were suitable candidates for perioperative beta-blockade by the American College
      of Physician guidelines. The retrospective phase studied 200 patients, of whom 63
      were suitable candidates, and assessed pre- and postoperative use of beta
      blockade. 40.6% and 38.1% of suitable patients received preoperative beta
      blockade in the two phases, respectively. Findings were similar in those
      undergoing vascular surgery, suggesting that perception of perioperative risk did
      not influence the decision to use beta-blockade. Beta-blockers were not
      prescribed preoperatively because of lack of knowledge about contraindications to
      beta-blockade, and anesthesiologist reluctance to prescribe oral medication to
      outpatients. DISCUSSION: Use of preoperative beta-blockade among suitable
      candidates appears to be approximately 40%. Anesthesiologists started
      preoperative beta-blockers infrequently even in patients without
      contraindications. These findings suggest that educating anesthesiologists about
      the perioperative use of beta-blockade may increase the use of this potentially
      beneficial strategy.

PMID- 15470165
TI  - Patient selection in ambulatory anesthesia - an evidence-based review: part I.
AB  - PURPOSE: To identify and characterize the evidence supporting decisions made in
      the care of patients with selected medical conditions undergoing ambulatory
      anesthesia and surgery. Conditions highlighted in this review include: the
      elderly, heart transplantation, hyper-reactive airway disease, coronary artery
      disease, and obstructive sleep apnea. SOURCE: A structured search of MEDLINE
      (1966-2003) was performed using keywords for ambulatory surgery and patient
      condition. Selected articles were assigned a level of evidence using Centre for
      Evidence Based Medicine (CEBM) criteria. Recommendations were also graded using
      CEBM criteria. PRINCIPAL FINDINGS: The elderly may safely undergo ambulatory
      surgery but are at increased risk for hemodynamic variation in the operating
      room. The heart transplant recipient is at increased risk of coronary artery
      disease and renal insufficiency and should undergo careful preoperative
      evaluation. The patient with reactive airway disease is at increased risk of
      minor respiratory complications and should be encouraged to quit smoking. The
      patient with coronary artery disease and recent myocardial infarction may undergo
      ambulatory surgery without stress testing if functional capacity is adequate. The
      patient with obstructive sleep apnea is at increased risk of difficult tracheal
      intubation but the likelihood of airway obstruction and apnea following
      ambulatory surgery is unknown. CONCLUSION: Ambulatory anesthesia is infrequently
      associated with adverse outcomes, however, knowledge regarding specific patient
      conditions is of generally low quality. Few prospective trials are available to
      guide management decisions.

PMID- 15470166
TI  - Patient selection in ambulatory anesthesia - an evidence-based review: part II.
AB  - PURPOSE: This is the second of two reviews evaluating the management of patients
      with selected medical conditions undergoing ambulatory anesthesia and surgery.
      Conditions highlighted in this review include: diabetes mellitus; morbid obesity;
      the ex-premature infant; the child with an upper respiratory infection; malignant
      hyperthermia; and the use of monoamine oxidase inhibitors. SOURCE: Medline search
      strategies and the framework for the evaluation of clinical evidence are
      presented in Part I. PRINCIPAL FINDINGS: Diabetes mellitus has not been linked
      with adverse events following ambulatory surgery. The morbidly obese patient is
      at an increased risk for minor respiratory complications in the perioperative
      period but these events do not increase unanticipated admissions. The ex
      premature infant may be considered for ambulatory surgery if post-conceptual age
      is > 60 weeks and hematocrit is > 30%. The child with a recent upper respiratory
      tract infection is at an increased risk for perioperative respiratory
      complications, particularly if endotracheal intubation is required. Patients with
      malignant hyperthermia may undergo outpatient surgery but require four hours of
      postoperative temperature monitoring. Sporadic cases of drug interactions have
      been reported when meperidine and indirect-acting catecholamines are administered
      in the presence of monamine oxidase inhibitors. Ambulatory anesthesia and surgery
      is safe if these combinations of drugs are avoided. CONCLUSION: Ambulatory
      anesthesia can be performed in, and is being offered to, a variety of patients
      with significant coexistent disease. In many cases there is little evidence
      documenting the outcomes expected in such patients. Prospective observational and
      interventional trials are required to better define perioperative management.

PMID- 15470167
TI  - Phonomyographic measurements of neuromuscular blockade are similar to
      mechanomyography for hand muscles.
AB  - PURPOSE: Phonomyography consists of recording low frequency sounds created during
      muscle contraction. In this study, phonomyography of three regions of the hand
      was compared to mechanomyography of the adductor pollicis. METHODS: In 12
      patients, phonomyography was recorded via small condenser microphones taped over
      the thenar mass, the hypothenar eminence, and the dorsal groove between the first
      and second metacarpal bones to record the acoustic signals of adductor pollicis
      and the hypothenar and first dorsal interosseus muscles, respectively.
      Mechanomyography of the adductor pollicis was recorded simultaneously using a
      force transducer. After induction of anesthesia, the ulnar nerve was stimulated
      supramaximally using train-of-four (TOF) stimulation every 12 sec. Onset, maximum
      effect, and offset of neuromuscular block after rocuronium 0.6 mg x kg(-1) were
      measured using phonomyography and compared to mechanomyography using ANOVA and
      the Bland-Altman test. RESULTS: Phonomyographic measurements of onset and maximum
      effect of neuromuscular blockade were not significantly different from
      mechanomyographic measurements. Phonomyographic measurements of offset (T25%, T75
      %, TOF 0.8) of neuromuscular block at the thenar muscles and first dorsal
      interosseus muscles were not significantly different from mechanomyographic
      measurements at adductor pollicis; however, T50%, T75% and T90% phonomyographic
      measurements at the hypothenar muscle were significantly shorter than at any
      other muscle site. CONCLUSION: There was good agreement between mechanomyographic
      measurements at the adductor pollicis muscle and phonomyographic measurements at
      the thenar and the first dorsal interosseus muscles. Phonomyography of those two
      muscles could be used interchangeably with mechanomyography of adductor pollicis
      for clinical purposes.

PMID- 15470168
TI  - Patient satisfaction with anesthesia care: information alone does not lead to
      improvement.
AB  - PURPOSE: To evaluate if information campaigns and introduction of information
      leaflets lead to an improvement in patient satisfaction with anesthesia care.
      METHODS: In 2000, we carried out an assessment of patient satisfaction with
      anesthesia care. "Information/involvement in decision making" was identified as
      the worst problem area. The three hospitals involved in this study introduced
      strategies to improve this dimension of patient satisfaction by launching
      information campaigns, producing or improving information brochures (particularly
      in hospitals A and C), and by expanding the preanesthetic care unit (hospital B).
      In 2002, a second survey was carried out. Each of the hospitals sent
      questionnaires to 600 elective surgery patients after discharge. We compared the
      total problem scores (the percentage of patients who responded that a problem was
      present) and the problem scores for the dimension 'information/involvement in
      decision making' between 2000 and 2002. RESULTS: The total problem score (mean in
      %, 95% confidence interval) for all three hospitals together remained unchanged
      [19% (1)], as well as the problem scores for each hospital [hospital A 16% (1),
      hospital B 21% (1), hospital C 20% (1)]. The problem score for
      'information/involvement in decision making' remained unchanged also: 31% (29-33)
      in 2000 compared to 28% (26-30) in 2002. CONCLUSION: Information campaigns and
      the introduction of information leaflets alone do not improve patient
      satisfaction with anesthesia care.

PMID- 15470169
TI  - [Severe bradycardia and asystole with low dose sufentanil during induction with
      sevoflurane: a report of three cases].
AB  - OBJECTIVES: In a randomized double blind clinical study using low doses of
      fentanyl or sufentanil during sevoflurane induction, we observed three cases of
      severe bradycardia, forcing us to discontinue the study. We wish to describe
      these three cases. CLINICAL DATA: Anesthesia was induced in the three patients,
      using a single breath technique consisting of a mixture of sevoflurane 8% with a
      nitrous oxide flow of 3 L x min(-1) and an oxygen flow of 3 L x min(-1). After
      the patients had lost consciousness, low dose sufentanil was administered (0.025
      microg x kg(-1) for the first patient and 0.1 microg x kg(-1) for the other two
      patients). Heart rate fell to 38, 40 and 42 beats x min(-1) respectively two
      minutes after the sufentanil injection in these three patients, and progressed to
      asystole in the third. All the patients responded to atropine 0.6 mg i.v.
      CONCLUSION: The addition of sufentanil, even at very low doses, during anesthesia
      induction with sevoflurane using a single breath technique, may be dangerous
      because of possible bradycardia and even asystole.

PMID- 15470170
TI  - Increased body mass index and ASA physical status IV are risk factors for block
      failure in ambulatory surgery - an analysis of 9,342 blocks.
AB  - PURPOSE: Regional anesthesia can be the technique of choice for selected
      ambulatory surgery procedures, but in spite of its benefits, it has an inherent
      failure rate even in experienced hands. We examine the efficacy and factors
      associated with failure of ambulatory regional anesthesia techniques. METHODS:
      This study included 9,342 blocks performed on 7,160 patients at the Duke
      University Ambulatory Surgery Center. Blocks were classified as interscalene,
      supraclavicular, axillary, lumbar plexus, femoral, sciatic, ankle, paravertebral,
      spinal, and other (frequency less than 100). A block was considered surgical if a
      single attempt at placing the block resulted in a complete sensory, motor, and
      sympathetic nerve block. Multiple logistic regression analyses were used to
      assess the risk-adjusted association between patient characteristics and block
      failure. RESULTS: Paravertebral blocks and those considered in the "other"
      category had significantly higher failure rates (P < 0.001), while spinal and
      lumbar plexus blocks had lower than average rates of failure (P < 0.001 and P =
      0.03, respectively). In multiple logistic regression analyses excluding
      paravertebral blocks, body mass index (BMI) scores greater than 25 (P values: BMI
      25-29: < 0.001; BMI 30-34: P < 0.001; BMI 35: P < 0.001) and ASA physical status
      IV (P < 0.001) were significantly associated with higher block failure rates.
      CONCLUSION: High BMI and ASA IV are independent risk factors for block failure in
      ambulatory surgery patients.

PMID- 15470171
TI  - Sciatic nerve block in the popliteal fossa: description of a new medial approach.
AB  - PURPOSE: Sciatic nerve blocks through lateral approaches in the popliteal fossa
      have been proposed. We describe a new medial approach to the sciatic nerve at
      this level. METHODS: After an anatomical study on six cadavers, we performed
      sciatic nerve blocks on 20 patients. A 100-mm insulated needle and a nerve
      stimulator were used; 20 mL of lidocaine 1.5% with epinephrine were injected.
      RESULTS: Patients lied in the supine position, the thigh flexed, abducted and
      rotated externally (30 degrees in all directions). The leg was flexed at 130
      degrees . In this position, above the adductor tubercle, a depression known as
      Jobert's fossa is palpated. Through this groove, a medial approach to the sciatic
      nerve at the level of the popliteal fossa is possible. The mean distance between
      the adductor tubercle and the puncture site is 6.18 cm (range 4-8 cm) and the
      mean distance between the skin and the sciatic nerve is 6.62 cm (range 4-9 cm).
      Mean time to perform the block was 100 sec (range 55-165 sec). Complete motor
      blockade was obtained after a mean time of 30 min (range 5-60 min) inside the
      common peroneal nerve area and 43 min (range 15-75 min) inside the tibial nerve
      area. Motor block was complete in 17 patients and sensory block in 18 patients.
      No vessel puncture was observed. CONCLUSION: We describe a new medial approach to
      the sciatic nerve in the popliteal fossa. More studies will be required to
      demonstrate the technique is effective and safe.

PMID- 15470172
TI  - Bilateral sixth cranial nerve palsy after unintentional dural puncture.
AB  - PURPOSE: Bilateral sixth nerve palsy is a known though uncommon complication
      following dural puncture. The recommended treatment consists of hydration and
      alternate monocular occlusion. The value and the timing of an epidural blood
      patch (EBP) for sixth nerve palsy remains controversial as some authors have
      demonstrated benefits in performing an EBP early in course of the nerve palsy
      whereas others have not found any advantage when an EBP was performed later.
      CLINICAL FEATURES: A 40-yr-old woman developed bilateral sixth nerve palsy ten
      days after an unintentional dural puncture. An EBP was done within 24 hr after
      the onset of the symptoms and immediate improvement of the diplopia was noted by
      the patient and confirmed by an ophthalmologist. Complete resolution of the
      diplopia occurred 36 days after the dural puncture. CONCLUSION: Blood patching
      within 24 hr of the onset of diplopia may be a reasonable treatment for ocular
      nerve palsy as it relieved the postdural puncture headache and produced partial
      improvement of the diplopia.

PMID- 15470173
TI  - Desflurane increases cerebral blood flow velocity when used for rapid emergence
      from propofol anesthesia in children.
AB  - PURPOSE: Desflurane may be used to replace propofol at the end of anesthesia to
      facilitate rapid emergence. This study determined the effect of administering
      desflurane during emergence of anesthesia on middle cerebral artery blood flow
      velocity (Vmca) in children anesthetized with propofol. METHODS: Thirty healthy
      children aged one to six years scheduled for orchidopexy or hypospadias repair
      under general anesthesia were enrolled. Anesthesia was maintained with a propofol
      infusion targeting an estimated serum level of 3 microg x mL(-1), remifentanil
      0.2 microg x kg(-1) x min(-1) and a caudal epidural block. Transcranial Doppler
      sonography was used to measure Vmca at five-minute intervals. In half the
      patients, propofol was substituted with desflurane 1 MAC, 30 min prior to the end
      of the surgical procedure. Once steady-state had been achieved recordings of
      Vmca, heart rate, and mean arterial pressure were resumed. Upon termination of
      the surgical procedure, the maintenance agent was discontinued and recordings
      continued at one-minute intervals during emergence of anesthesia. RESULTS: There
      were no demographic differences between the two groups. Vmca increased from 37.2
      +/- 3.1 cm x sec(-1) to 57.7 +/- 4.1 cm x sec(-1) when propofol was changed to
      desflurane (P < 0.01). Upon emergence of anesthesia, Vmca decreased from 57.8 +/-
      4.2 cm x sec(-1) to 37.8 +/- 3.2 cm x sec(-1) in the desflurane group (P < 0.01)
      but remained unchanged in the propofol group. CONCLUSION: Desflurane is
      associated with an increase in cerebral blood flow velocity when used to
      facilitate rapid emergence following a propofol infusion in children. This may be
      of clinical significance in patients with intracranial pathology.

PMID- 15470174
TI  - Decreased heart rate and blood pressure in a recent cardiac transplant patient
      after spinal anesthesia.
AB  - PURPOSE: To describe the cardiovascular effects of neuraxial blockade in a heart
      transplant patient. CLINICAL FEATURES: A 69-yr-old 70-kg male underwent
      orthotopic heart transplant (bicaval anastomosis technique) for ischemic
      cardiomyopathy. Five months after transplantation, the patient underwent a
      transurethral bladder tumour resection under spinal anesthesia. Two millilitres
      of bupivacaine 0.75% (15 mg) were injected intrathecally at L(3-4) and the
      patient remained seated for approximately 20 sec prior to assuming the lithotomy
      position. Subsequently, both blood pressure (BP) and heart rate (HR) diminished
      gradually (BP and HR immediately pre-spinal: 113 mmHg (mean arterial pressure)
      and 92 beats x min(-1), respectively; nadir BP and HR: 94 mmHg (16.8% decrease)
      30 min postspinal and 73 beats x min(-1) (20.7% decrease) 40 min postspinal,
      respectively). HR and mean BP were highly correlated (r = 0.9410, P < 0.0001,
      R(2) = 0.8854). The dermatome level of neuraxial anesthesia, determined by
      sensitivity to pin prick, was T(8) (five minutes) and T(6) (ten minutes)
      postinjection of spinal anesthetic. Control patients (n = 10) undergoing elective
      urological procedures with identical anesthesia management demonstrated very
      similar cardiovascular responses. CONCLUSIONS: Although cardiac transplant
      patients may tolerate neuraxial anesthesia admirably, a fall in HR may ensue
      which theoretically could have important physiological consequences. It is argued
      that the change in HR in the transplanted patient was mediated by mechanisms
      intrinsic to the transplanted heart and/or by reduced catecholamine secretion
      from the adrenal medulla. It is emphasized that HR changes observed in cardiac
      transplant patients do not necessarily imply reinnervation of the transplanted
      organ.

PMID- 15470175
TI  - In cadavers, directly measured mucosal pressures are similar for the Unique and
      the Soft Seal laryngeal mask airway devices.
AB  - PURPOSE: We compare the Soft Seal and Unique single-use, plastic laryngeal mask
      airway devices with respect to intracuff pressure, directly measured mucosal
      pressure and in vitro elastance. METHODS: Ten fresh male cadavers were studied.
      Microchip pressure sensors were attached to the following locations: A) the
      anterior middle part of the cuff side; B) the posterior tip of the cuff; C) the
      anterior base of the cuff; D) the posterior middle part of the cuff side; E) the
      backplate; and F) the posterior tube. The size 5 Unique and size 5 Soft Seal were
      inserted in random order using laryngoscope-guidance. Intracuff pressure and
      mucosal pressure were documented at 0 to 40 mL cuff volume in 10 mL increments.
      In vitro elastance was determined between 20 to 40 mL cuff volume. RESULTS: For
      both devices, mucosal pressure increased with cuff volume at most locations.
      Intracuff pressures and in vitro elastance (5.2 +/- 0.7 cm H(2)O/mL vs 3.8 +/-
      0.4 cm H(2)O/mL, P < 0.0001) were higher for the Unique than the Soft Seal (P <
      0.0001), but there were no differences in mucosal pressures at any location or
      cuff volume. CONCLUSION: Intracuff pressures and in vitro elastance are higher
      for the Unique than the Soft Seal, but mucosal pressures are similar suggesting
      that the airway morbidity will be similar.

PMID- 15470176
TI  - Total airway obstruction during local anesthesia in a non-sedated patient with a
      compromised airway.
AB  - PURPOSE: To report a case of complete upper airway obstruction after
      topicalization with lidocaine in a completely conscious patient with partial
      upper airway obstruction. CLINICAL FEATURES: A 69-yr-old man with a history of
      neck cancer and radiation presented for resection of recurrent neck tumour. No
      preoperative sedation was given. He had inspiratory and expiratory stridor but
      had no history of aspiration or swallowing problem. Phonation was distorted but
      effective. The surgeon was reluctant to perform an awake tracheostomy under local
      anesthesia. In preparation for a fibrescope-assisted orotracheal intubation, the
      non-sedated patient was given topical upper airway lidocaine during which he
      developed total airway obstruction and hypoxemia. He was immediately intubated
      with a fibrescope. His vocal cords were not edematous although the supraglottic
      structures appeared to be. The vocal cords were abducted and their movement was
      limited and not paradoxical. Tumour resection was uneventful upon successful
      tracheal intubation and general anesthesia. Tracheostomy at the end of the case
      was difficult, as expected. The patient tolerated the procedures and regained
      consciousness with no neurologic sequelae. CONCLUSION: Dynamic airflow limitation
      associated with local anesthesia of the upper airway may lead to complete upper
      airway obstruction in a compromised airway. The main cause may be the loss of
      upper airway muscle tone, exacerbated by deep inspiration during panic.

PMID- 15470178
TI  - Best evidence in critical care medicine: treatment of submassive pulmonary
      embolism.

PMID- 15470177
TI  - Laryngo-tracheo-bronchial stenosis in a patient with primary pulmonary
      amyloidosis: a case report and brief review.
AB  - PURPOSE: To report a case of lower respiratory tract obstruction occurring in a
      patient with primary pulmonary amyloidosis and discuss anesthetic management.
      CLINICAL FEATURES: A 53-yr-old man was referred to our institution for
      microlaryngoscopy and laser treatment of the larynx. He presented with a five
      year history of primary laryngo-tracheo-bronchial amyloidosis and symptoms
      consistent with narrowing of the conducting airways. General anesthesia was
      induced with iv propofol 150 mg and remifentanil 50 microg. Mivacurium 20 mg
      provided muscle relaxation for endotracheal intubation. Following endotracheal
      intubation, the airway became obstructed and patient ventilation impossible. The
      endotracheal tube was removed and a Dedo laryngoscope inserted. Gas exchange was
      maintained using supraglottic jet ventilation via a distal port of the
      laryngoscope. Rigid bronchoscopy showed tissue partially obstructing the lumen of
      the lower trachea. This was removed and the airway appeared patent. At the end of
      the case, a further episode of lower airway obstruction occurred requiring
      reinsertion of the laryngoscope and resumption of jet ventilation. Extensive
      debridement through the bronchoscope was required before adequate ventilation
      could be restored. Some days later when the patient's condition deteriorated
      again and he required further debridement of the trachea and insertion of a
      tracheostomy, guide wires were positioned in the femoral vessels in the event
      that cardiopulmonary bypass was required for gas exchange. CONCLUSIONS: Primary
      laryngo-tracheo-bronchial amyloidosis is a recurrent disease, requiring
      repetitive surgical procedures. Airway compromise can be a persistent problem.
      Awareness of this uncommon disease process and its presentation may serve to
      caution the anesthesiologist presented with this type of case.

PMID- 15470180
TI  - Coronary spasm in a 59-yr-old woman with hyperventilation.

PMID- 15470181
TI  - Ropivacaine plasma concentrations are similar during continuous lumbar plexus
      blockade using two techniques: pharmacokinetics or pharmacodynamics?

PMID- 15470182
TI  - [Paravertebral blockade is not a suitable anesthetic technique for ambulatory
      minor breast surgery].

PMID- 15470183
TI  - Accidental administration of succinylcholine for the treatment of hypotension in
      a labouring parturient.

PMID- 15470184
TI  - Drug labelling and a near miss in the labour suite.

PMID- 15470185
TI  - Narcotrend depth of anesthesia monitoring in infants and children.

PMID- 15470186
TI  - Atropine-triggered idiopathic ventricular tachycardia in an asymptomatic
      pediatric patient.

PMID- 15470187
TI  - Rapid sequence intubation: how do we define success?

PMID- 15470188
TI  - Rapid sequence intubation: how do we define success?

PMID- 15470189
TI  - Gum elastic bougie-guided insertion of the LMA-ProSeal in occult tonsillar
      hypertrophy.

PMID- 15470190
TI  - Fanning the flames.

PMID- 15470191
TI  - Genes, longevity, and technology: meeting report from the 2nd conference on
      functional genomics of aging in Crete.
AB  - Whole-genome sequences are now available, and methods have evolved for targeting,
      in parallel, each gene in a genome, offering for the first time the opportunity
      to study the entire dynamic network of genes involved in aging. At a recent
      conference in Hersonissos, Crete, around 200 internationally renowned experts
      gathered to discuss techniques and emerging results as the science of aging
      undergoes a shift toward systems biology.

PMID- 15470192
TI  - Coxibs and cardiovascular disease.

PMID- 15470193
TI  - Failing the public health--rofecoxib, Merck, and the FDA.

PMID- 15470194
TI  - Evidence of oxidative stress in full-term healthy infants.
AB  - We hypothesized that early infancy would be a time of oxidative stress due to the
      difficulty of adapting to ambient oxygen. Therefore, we measured levels of
      products of lipid peroxidation (F2-isoprostanes), antioxidant enzyme activity
      (catalase (CAT) and superoxide dismutase (SOD)), and ability to resist oxidative
      stress (ferric reducing ability of plasma (FRAP)) in full-term infants (38-42 wk)
      fed human milk from birth. Seventy-seven infants were followed at 1, 3.5, 6, and
      12 mo of age. F2-isoprostanes in plasma declined significantly (p < 0.05) from 1
      to 6 mo (160 +/- 43; 90 +/- 33; 41 +/- 27 pg/mL (mean +/- SD)). FRAP values (775
      +/- 196, 723 +/- 133, 697 +/- 126, 669 +/- 145 microM) 1, 3.5, 6, and 12,
      respectively) declined (p = 0.06) from 1 to 3.5 mo and from 3.5 to 6 mo of age.
      RBC-SOD (2.7 +/- 2, 3.2 +/- 2.8, 2.1 +/- 1.8, 2.5 +/- 1.8 U, 1, 3.5, 6, 12 mo,
      respectively) declined from 3.5 to 6 mo. RBC-CAT (76 +/- 23, 94 +/- 28, 81 +/-
      22, 85 +/- 31 U, 1, 3.5, 6, 12 mo, respectively) also declined between 3.5 and 6
      mo, after a significant increase between 1 and 3.5 mo. These data suggest that
      the human infant is under oxidative stress early in infancy and further study may
      be warranted to assess the potential benefits of antioxidant supplementation for
      either the mother or the infant.

PMID- 15470195
TI  - Role of heme oxygenase and bilirubin in oxidative stress in preterm infants.
AB  - In a previous study, it was found that the decrease in the total plasma bilirubin
      level (Btot) in preterm infants was associated with the decrease in oxidative
      stress. We hypothesized that this occurs as a result of a pro-oxidant effect of
      heme oxygenase (HO), which outcompetes with the antioxidant properties of
      bilirubin. In this study we studied 12 preterm infants in whom the plasma levels
      of Btot, total hydroperoxide (TH), protein SH groups, HO activity, non
      transferrin-bound iron (NTBI), and erythrocyte CuZn superoxide dismutase (CuZn
      SOD) activity were concurrently measured when the Btot was >220 microM and after
      a Btot drop of >34 microM. The Btot decrease was concurrent with the TH decrease,
      protein SH groups increase, and the HO and CuZn SOD activity increase and was not
      associated with an NTBI increase. We concluded that 1) Btot does not exert a
      meaningful antioxidant effect in vivo; 2) HO does not exert a pro-oxidant effect
      involving an NTBI increase and that, on the contrary, it could exert an
      antioxidant effect; and 3) the concurrent HO and CuZn SOD activity increase could
      indicate a synergic antioxidant effect of the two enzymes.

PMID- 15470196
TI  - Association of vascular endothelial growth factor (VEGF) and VEGF receptor gene
      polymorphisms with coronary artery lesions of Kawasaki disease.
AB  - We analyzed the genetic polymorphisms of vascular endothelial growth factor
      (VEGF) and its receptors [Fms-related tyrosine kinase-1, kinase insert domain
      receptor (KDR)] in Japanese patients with Kawasaki disease (KD) and normal
      control subjects to examine whether these genes would contribute to the KD
      occurrence and/or the development of coronary artery lesion (CAL) in KD. We found
      that the frequency of G allele of VEGF g.-634 G>C single-nucleotide polymorphism
      in the promoter region was significantly higher in KD patients with CAL than in
      those without CAL (p = 0.012) or control subjects (p = 0.021) because of a
      significantly higher frequency of the GG genotype in KD patients with CAL. In
      addition, the frequency of the A1 allele with 11 AC repeats of KDR g.+4422(AC)11
      14 dinucleotide repeat polymorphism in intron 2 was significantly higher in KD
      patients with CAL than in those without CAL (p = 0.013) or control subjects (p =
      0.040) as a result of a significantly higher frequency of the A1A1 genotype in KD
      with CAL patients. The multivariate analysis of clinical features and genotypes
      of the two polymorphisms showed that the A1A1 genotype of KDR g.+4422(AC)11-14
      polymorphism was an independent risk factor for the development of CAL with the
      highest odds ratio among several clinical parameters (odds ratio 6.76; 95%
      confidence interval 1.05-43.48). Dual luciferase assay demonstrated that the A1
      allele with KDR g.+4422(AC)11 repeats showed a weaker silencer function than the
      A2 allele with 12 AC repeats. These findings suggested that VEGF and its
      receptor, KDR, genes contributed to the development of CAL in KD patients.

PMID- 15470197
TI  - Extracellular receptor kinase and cAMP response element binding protein
      activation in the neonatal rat heart after perinatal cocaine exposure.
AB  - Prenatal exposure to cocaine has been shown to induce an increase in the
      myocardial expression and activation of the cAMP response binding protein (CREB),
      a transcriptional factor that has been shown to regulate gene expression. Several
      different kinases, including protein kinase A, calcium calmodulin kinase II, and
      mitogen-activated protein kinase can induce phosphorylation of CREB at serine
      133, a necessary step for CREB activation. We examined whether the mitogen
      activated protein kinase-extracellular receptor kinase (ERK) pathway may be
      involved in mediating the serine 133 CREB phosphorylation in cardiac nuclei after
      perinatal cocaine exposure. Pregnant rats were treated daily with saline or
      cocaine at 60 mg/kg (C60) by intragastric administration during the entire
      gestational period, and treatment was continued in the nursing dams after
      delivery until the time of the study. Nuclear extracts were isolated from hearts
      of 1-d- and 7-d-old neonatal rats. We performed immunoblotting experiments using
      an antibody that recognized CREB with phosphorylation specifically at the serine
      133 site and an antibody that recognized both the phosphorylated and the
      unphosphorylated forms of CREB, as well as antibodies for total ERK, phospho-ERK,
      total ribosomal S6 kinase 1 (RSK1), RSK2, and phospho-RSK. We assessed the
      interaction of RSK with CREB or CREB-binding protein by performing co
      immunoprecipitation experiments. We found that perinatal cocaine exposure
      increased both phospho-ERK and phospho-RSK expression, indicative of an increased
      activity of these two enzymes. Furthermore, we demonstrated that phospho-RSK was
      immunoprecipitated with CREB in all neonatal cardiac nuclei and that the greatest
      interaction was found in day 7 hearts after perinatal cocaine exposure. Our
      results thus illustrate that the ERK-RSK pathway was active in the postnatal rat
      heart at 1 and 7 d of age and that this pathway may mediate the increase in
      myocardial CREB activation after perinatal cocaine exposure in the day 7 hearts.

PMID- 15470198
TI  - Oral mucosal microvascular abnormalities: an early marker of bronchopulmonary
      dysplasia.
AB  - An abnormal pulmonary vasculature has been reported as an important component of
      bronchopulmonary dysplasia (BPD). We tested the hypothesis of an early abnormal
      vascular network pattern in infants with BPD. Fifteen infants with BPD (nine boys
      and six girls; gestational age 27.5 +/- 2.0 wk; birth weight 850 +/- 125 g) and
      15 sex- and gestational age-matched infants (nine boys and six girls; gestational
      age 27.6 +/- 2.6 wk; birth weight 865 +/- 135 g) were examined on postnatal days
      1 and 28. BPD infants showed a significantly higher prevalence of histologic
      chorioamnionitis (p = 0.009), as well as higher intubation duration (p = 0.0004),
      oxygen supplementation (p < 0.0001), and initial illness severity (p = 0.0002)
      than the BPD-negative population. The lower gingival and vestibular oral mucosa
      was chosen as the study area. The blood vessel area was determined, and the oral
      vascular networks were characterized by analyzing their complexity (D, at two
      scales: D 1-46, D 1-15), tortuosity (Dmin), and randomness (L-Z) of the vascular
      loops. Infants with BPD showed a significantly lower blood vessel area as well as
      a higher vascular network complexity (D 1-46, D 1-15, and L-Z) than control
      subjects (p < 0.0001). Our findings provide a new early clinical sign in BPD and
      stress the importance of an early disorder in the oral mucosal vascularization
      process in the disease pathogenesis.

PMID- 15470199
TI  - Perinatal salt restriction: a new pathway to programming insulin resistance and
      dyslipidemia in adult wistar rats.
AB  - Several studies support the hypothesis that chronic diseases in adulthood might
      be triggered by events that occur during fetal development. This study examined
      the consequences of perinatal salt intake on blood pressure (BP) and carbohydrate
      and lipid metabolism in adult offspring of dams on high-salt [HSD; 8% (HSD2) or
      4% (HSD1)], normal-salt (NSD; 1.3%), or low-salt (LSD; 0.15% NaCl) diet during
      pregnancy and lactation. At 12 wk of age, female Wistar rats were matched with
      adult male rats that were fed NSD. Weekly tail-cuff BP measurements were
      performed before, during, and after pregnancy. After weaning, the offspring
      received only NSD and were housed in metabolic cages for 24-h urine collection
      for sodium and potassium and nitrate and nitrite excretion measurements. At 12 wk
      of age, intra-arterial mean BP was measured, a euglycemic-hyperinsulinemic clamp
      was performed, and plasma lipids and nitrate and nitrite concentrations were
      determined. Tail-cuff BP was higher during pregnancy in HSD2 and HSD1 than in NSD
      and LSD dams. Mean BP (mm Hg) was also higher in the offspring of HSD2 (110 +/-
      5) and HSD1 (107 +/- 5) compared with NSD (100 +/- 2) and LSD (92 +/- 2). Lower
      glucose uptake and higher plasma cholesterol and triacylglycerols were observed
      in male offspring from LSD dams (glucose uptake: HSD2 17 +/- 4, HSD1 15 +/- 3,
      NSD 11 +/- 3, LSD 4 +/- 1 mg . kg(-1) . min(-1); cholesterol: HSD2 62 +/- 6, HSD1
      82 +/- 11, NSD 68 +/- 10, LSD 98 +/- 17 mg/dL; triacylglycerols: HSD2 47 +/- 15,
      HSD1 49 +/- 12, NSD 56 +/- 19, LSD 83 +/- 11 mg/dL). In conclusion, maternal salt
      intake during pregnancy and lactation has long-term influences on arterial
      pressure, insulin sensitivity, and plasma lipids of the adult offspring.

PMID- 15470200
TI  - Cardiovascular autonomic regulation in preterm infants: the effect of atropine.
AB  - To study cardiovascular autonomic control, we assessed the effect of atropine on
      heart rate (HR) and blood pressure (BP) variability in 12 preterm infants (range
      26-32 wk) before intubation for respiratory insufficiency. Spectral power
      analysis of R-R interval and systolic BP (SBP) series were estimated in a low
      frequency (LF; 0.04-0.15 Hz) and high-frequency (HF; 0.4-1.5 Hz) band and
      evaluated for a 10-min period before and a 10-min period after atropine sulfate
      (0.01 mg/kg). Baroreceptor reflex (BR) functioning was estimated using transfer
      function analysis at LF (coherence, gain, and phase). Atropine resulted in a
      significant 12% increase in steady-state HR (p < 0.01) and unchanged SBP. For R-R
      interval series, the total spectral power decreased 6-fold (p < 0.01), which was
      predominantly due to a reduction in the LF band (16-fold; p < 0.01). In contrast,
      we observed a significant increase (25%; p < 0.05) in total spectral power of SBP
      series partly as a result of an increase in HF power. The LF power of SBP series
      was not altered. The median LF transfer gain (BR sensitivity) between SBP and R-R
      interval decreased from 4.2 to 1.4 ms/mm Hg (p < 0.01) after atropine. The LF
      phase relationship (BP leads R-R interval fluctuations by approximately 4 s) was
      not changed after atropine. In conclusion, even in preterm infants in distress,
      atropine modulates HR and BP variability, suggesting that BR-mediated
      parasympathetic control of heart rate is of significance for cardiovascular
      control at that age.

PMID- 15470201
TI  - Pentoxifylline reduces regional inflammatory and ventilatory disturbances in
      meconium-exposed piglet lungs.
AB  - Neonatal meconium aspiration frequently produces severe respiratory distress,
      which is associated with patchy pulmonary neutrophil influx and inflammatory
      injury. To examine the effects of pentoxifylline (PTX), a potent anti
      inflammatory agent, on regional pulmonary inflammation and ventilation after
      meconium aspiration, we studied 17 anesthetized and ventilated neonatal piglets
      (age <2 d) for 12 h. After unilateral intrapulmonary instillation of meconium,
      PTX treatment was started in nine animals, and eight untreated animals served as
      controls. Bronchoalveolar lavage (BAL) fluid and lung tissue were studied for
      inflammatory variables at the end of the study, and changes in regional
      ventilation were serially analyzed with a dynamic pulmonary x-ray imaging method.
      Meconium insufflation increased BAL fluid total cell, neutrophil, and macrophage
      counts and tumor necrosis factor-alpha (TNF-alpha) and protein concentrations as
      well as lung tissue myeloperoxidase activity in the instilled lungs, compared
      with the noninstilled side. PTX treatment prevented the increase of BAL fluid
      alveolar macrophage count and TNF-alpha and protein concentrations in the
      meconium-instilled lungs but had no significant effect on the pulmonary
      neutrophil accumulation. Ventilation of the meconium-insulted lung was initially
      disturbed similarly in both study groups, but PTX administration prevented the
      sustained local ventilatory perturbation at 4, 6, and 12 h after meconium
      instillation. The results thus indicate that PTX treatment may attenuate meconium
      induced regional ventilation derangements, mainly through its effects on local
      alveolar macrophages and TNF-alpha production as well as alveolocapillary
      permeability rather than via significant prevention of accumulation of active
      neutrophils in the insulted lungs.

PMID- 15470202
TI  - Natural infection of infants with respiratory syncytial virus subgroups A and B:
      a study of frequency, disease severity, and viral load.
AB  - Heterogeneity in respiratory syncytial virus (RSV) disease severity likely is due
      to a combination of host and viral factors. Infection with RSV subgroup A is
      thought to produce more severe disease than RSV-B. Higher RSV loads correlate
      with greater disease severity in hospitalized infants. Whether subgroup-specific
      variations in disease severity result from differences in RSV load has not been
      studied. A total of 102 RSV-hospitalized infants <2 y of age were studied. Nasal
      washes were collected in a standardized manner and were cultured in <3 h in
      parallel with an RSV quantitative standard in a HEp-2 plaque assay. RSV-A (72%)
      was more frequent than RSV-B. Disease severity risk factors were similar between
      subgroups. RSV loads were similar between A and B subgroups (4.77 versus 4.68 log
      PFU/mL). Measures of disease severity were also similar between subgroups.

PMID- 15470203
TI  - Influence of fetal breathing movements on pulmonary hemodynamics in fetal sheep.
AB  - During fetal development, pulmonary vascular resistance (PVR) is high, and, as a
      result, blood flow through the fetal lungs is low. Although PVR markedly
      decreases at the time of birth, the factors that regulate pulmonary blood flow
      (PBF) and PVR before and immediately after birth are not clear. Our aim was to
      examine the relationship between episodes of fetal breathing movements (FBM) and
      pulmonary hemodynamics during late gestation to further understand the
      relationship among lung luminal volume, phasic changes in intrapulmonary
      pressure, and PVR before birth. In chronically catheterized fetal sheep (120-128
      d gestation; n = 5; term approximately 147 d), PBF and PVR were measured during
      periods of FBM and apnea. Episodes of FBM were divided into periods of
      accentuated (amplitude of >3.5 mm Hg change in tracheal pressure) and
      nonaccentuated periods of FBM. During accentuated episodes of FBM, mean PBF was
      increased to 159.5 +/- 23.4% (p < 0.0025) of the preceding apneic period and was
      associated with a 19.1 +/- 5.2% reduction in PVR. In addition, during accentuated
      episodes of FBM, the retrograde flow of blood through the left pulmonary artery
      was reduced to 90.1 +/- 1.0% of the preceding apneic period, which most likely
      contributed to the increase in mean PBF at this time. Although a change in PBF
      and PVR could not be detected during nonaccentuated FBM, compared with the
      preceding apneic period, PBF was linearly and positively correlated with the
      amplitude (change in pressure) of FBM. We conclude that PVR is decreased and PBF
      is increased during accentuated episodes of FBM, possibly as a result of phasic
      reductions in intrapulmonary pressures.

PMID- 15470204
TI  - Pituitary-adrenal responses to acute hypoxemia during and after maternal
      dexamethasone treatment in sheep.
AB  - The effects of maternal dexamethasone treatment on hypothalamic-pituitary-adrenal
      axis function were determined during basal and hypoxemic conditions in maternal
      and fetal sheep. Under halothane, ewes and their fetuses were catheterized at 117
      d gestation (term = 145 d). Starting at 124 d, the ewes received i.m. injections
      of two doses of either dexamethasone (12 mg) or saline at 24-h intervals. All
      animals experienced one episode of hypoxemia when the dexamethasone was present
      in the maternal and fetal circulations [125 +/- 1 d (H1)] and a second episode of
      hypoxemia when the steroid was no longer detectable in either the maternal or
      fetal circulations [128 +/- 1 d (H2)]. The fall in partial pressure of oxygen in
      arterial blood in response to hypoxia was similar in the two episodes in both the
      fetal and the maternal blood. Maternal dexamethasone treatment diminished
      maternal and fetal basal plasma cortisol but not ACTH during the normoxic period
      of H1 but not H2. In control animals, hypoxemia induced increases in fetal but
      not maternal ACTH and cortisol concentrations. In dexamethasone-treated animals,
      maternal ACTH and cortisol concentrations also remained unchanged from baseline
      in both H1 and H2. In contrast, fetal plasma ACTH and cortisol responses to
      hypoxemia were significantly suppressed during H1 but not H2. Correlation of
      fetal plasma ACTH and cortisol concentrations suggested diminished cortisol
      output without a change in adrenocortical responsiveness in dexamethasone-treated
      fetuses during H1 but not H2. Maternal treatment with dexamethasone transiently
      suppressed maternal and fetal basal hypothalamic-pituitary-adrenal axis function
      and the fetal plasma ACTH and cortisol responses to acute hypoxemia in sheep.

PMID- 15470206
TI  - Protecting the uninsured.

PMID- 15470205
TI  - Angiotensin-converting enzyme and angiotensin type 2 receptor gene genotype
      distributions in Italian children with congenital uropathies.
AB  - Angiotensin I-converting enzyme (ACE) and angiotensin type 2 receptor (AT2R) gene
      polymorphisms have been associated with an increased incidence of congenital
      anomalies of the kidney and urinary tract (CAKUT). We investigated the genotype
      distribution of these polymorphisms in Italian children with CAKUT. We also
      evaluated the association between the ACE insertion/deletion and the AT2R gene
      polymorphisms with the progression of renal damage in subgroups of CAKUT
      patients. We recruited 102 Italian children with CAKUT; 27 with vesicoureteral
      reflux; 12 with hypoplastic kidneys; 20 with multicystic dysplastic kidneys; 13
      with ureteropelvic junctions stenosis/atresia; 18 with nonobstructed,
      nonrefluxing primary megaureters; and 12 with posterior urethral valves and
      compared them with 92 healthy control subjects. ACE and AT2R gene polymorphisms
      were analyzed by PCR. The identification of AT2R gene polymorphisms in intron 1
      and in exon 3 was revealed by enzymatic digestion. ACE genotype distribution in
      children with CAKUT was no different from that of the control subjects, but the
      subgroup of patients with radiographic renal parenchymal abnormalities showed an
      increased occurrence of the D/D genotype. The frequency of the G allele of AT2R
      gene in children with CAKUT was increased in respect to that of the control
      subjects. By contrast, no significant difference in the frequency of the C and A
      alleles of the AT2R gene was found. Our findings indicate that the ACE gene can
      be a risk factor in the progression of renal parenchymal damage in CAKUT
      patients. Moreover, a major role of the AT2R gene in the development of CAKUT has
      been found, at least in Italian children.

PMID- 15470207
TI  - Isolation of poliovirus--John Enders and the Nobel Prize.

PMID- 15470208
TI  - Advances in virology--Weller and Robbins.

PMID- 15470209
TI  - From culture to vaccine--Salk and Sabin.

PMID- 15470210
TI  - Mechanisms of androgen-refractory prostate cancer.

PMID- 15470211
TI  - Genotypes and phenotypes--another lesson from the hemoglobinopathies.

PMID- 15470212
TI  - Protected carotid-artery stenting versus endarterectomy in high-risk patients.
AB  - BACKGROUND: Carotid endarterectomy is more effective than medical management in
      the prevention of stroke in patients with severe symptomatic or asymptomatic
      atherosclerotic carotid-artery stenosis. Stenting with the use of an emboli
      protection device is a less invasive revascularization strategy than
      endarterectomy in carotid-artery disease. METHODS: We conducted a randomized
      trial comparing carotid-artery stenting with the use of an emboli-protection
      device to endarterectomy in 334 patients with coexisting conditions that
      potentially increased the risk posed by endarterectomy and who had either a
      symptomatic carotid-artery stenosis of at least 50 percent of the luminal
      diameter or an asymptomatic stenosis of at least 80 percent. The primary end
      point of the study was the cumulative incidence of a major cardiovascular event
      at 1 year--a composite of death, stroke, or myocardial infarction within 30 days
      after the intervention or death or ipsilateral stroke between 31 days and 1 year.
      The study was designed to test the hypothesis that the less invasive strategy,
      stenting, was not inferior to endarterectomy. RESULTS: The primary end point
      occurred in 20 patients randomly assigned to undergo carotid-artery stenting with
      an emboli-protection device (cumulative incidence, 12.2 percent) and in 32
      patients randomly assigned to undergo endarterectomy (cumulative incidence, 20.1
      percent; absolute difference, -7.9 percentage points; 95 percent confidence
      interval, -16.4 to 0.7 percentage points; P=0.004 for noninferiority, and P=0.053
      for superiority). At one year, carotid revascularization was repeated in fewer
      patients who had received stents than in those who had undergone endarterectomy
      (cumulative incidence, 0.6 percent vs. 4.3 percent; P=0.04). CONCLUSIONS: Among
      patients with severe carotid-artery stenosis and coexisting conditions, carotid
      stenting with the use of an emboli-protection device is not inferior to carotid
      endarterectomy.

PMID- 15470213
TI  - Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate
      cancer.
AB  - BACKGROUND: Mitoxantrone plus prednisone reduces pain and improves the quality of
      life in men with advanced, hormone-refractory prostate cancer, but it does not
      improve survival. We compared such treatment with docetaxel plus prednisone in
      men with this disease. METHODS: From March 2000 through June 2002, 1006 men with
      metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice
      daily and were randomly assigned to receive 12 mg of mitoxantrone per square
      meter of body-surface area every three weeks, 75 mg of docetaxel per square meter
      every three weeks, or 30 mg of docetaxel per square meter weekly for five of
      every six weeks. The primary end point was overall survival. Secondary end points
      were pain, prostate-specific antigen (PSA) levels, and the quality of life. All
      statistical comparisons were against mitoxantrone. RESULTS: As compared with the
      men in the mitoxantrone group, men in the group given docetaxel every three weeks
      had a hazard ratio for death of 0.76 (95 percent confidence interval, 0.62 to
      0.94; P=0.009 by the stratified log-rank test) and those given weekly docetaxel
      had a hazard ratio for death of 0.91 (95 percent confidence interval, 0.75 to
      1.11; P=0.36). The median survival was 16.5 months in the mitoxantrone group,
      18.9 months in the group given docetaxel every 3 weeks, and 17.4 months in the
      group given weekly docetaxel. Among these three groups, 32 percent, 45 percent,
      and 48 percent of men, respectively, had at least a 50 percent decrease in the
      serum PSA level (P<0.001 for both comparisons with mitoxantrone); 22 percent, 35
      percent (P=0.01), and 31 percent (P=0.08) had predefined reductions in pain; and
      13 percent, 22 percent (P=0.009), and 23 percent (P=0.005) had improvements in
      the quality of life. Adverse events were also more common in the groups that
      received docetaxel. CONCLUSIONS: When given with prednisone, treatment with
      docetaxel every three weeks led to superior survival and improved rates of
      response in terms of pain, serum PSA level, and quality of life, as compared with
      mitoxantrone plus prednisone.

PMID- 15470215
TI  - Lamivudine for patients with chronic hepatitis B and advanced liver disease.
AB  - BACKGROUND: The effectiveness of antiviral therapy in preventing disease
      progression in patients with chronic hepatitis B and advanced fibrosis or
      cirrhosis is unknown. METHODS: Patients with chronic hepatitis B who had
      histologically confirmed cirrhosis or advanced fibrosis were randomly assigned in
      a 2:1 ratio to receive lamivudine (100 mg per day) or placebo for a maximum of
      five years. Of 651 patients, 436 were assigned to receive lamivudine and 215 to
      receive placebo. The primary end point was time to disease progression, defined
      by hepatic decompensation, hepatocellular carcinoma, spontaneous bacterial
      peritonitis, bleeding gastroesophageal varices, or death related to liver
      disease. An independent data and safety monitoring board monitored the progress
      of the study and performed interim analyses of the data. RESULTS: We randomly
      assigned 651 patients (98 percent Asian and 85 percent male) to receive
      lamivudine or placebo. The study was terminated after a median duration of
      treatment of 32.4 months (range, 0 to 42) owing to a significant difference
      between treatment groups in the number of end points reached. End points were
      reached by 7.8 percent of the patients receiving lamivudine and 17.7 percent of
      those receiving placebo (hazard ratio for disease progression, 0.45; P=0.001).
      The Child-Pugh score increased in 3.4 percent of the patients receiving
      lamivudine and 8.8 percent of those receiving placebo (hazard ratio, 0.45;
      P=0.02), whereas hepatocellular carcinoma occurred in 3.9 percent of those in the
      lamivudine group and 7.4 percent of those in the placebo group (hazard ratio,
      0.49; P=0.047). Genotypic resistance YMDD mutations developed in 49 percent of
      the patients treated with lamivudine, and the Child-Pugh score was more likely to
      increase in patients with these mutations than in the other patients treated with
      lamivudine (7 percent vs. <1 percent). Overall, 12 percent of the patients in the
      lamivudine group and 18 percent of the patients in the placebo group reported
      serious adverse events. CONCLUSIONS: Continuous treatment with lamivudine delays
      clinical progression in patients with chronic hepatitis B and advanced fibrosis
      or cirrhosis by significantly reducing the incidence of hepatic decompensation
      and the risk of hepatocellular carcinoma.

PMID- 15470216
TI  - Hemoglobin Jamaica plain--a sickling hemoglobin with reduced oxygen affinity.
AB  - A baby girl presented with symptomatic sickle cell disease exacerbated by mild
      hypoxemia, despite a newborn-screening diagnosis of sickle cell trait. DNA
      sequencing of the beta globin gene revealed that her maternal beta globin allele
      was normal. Her paternal allele had not only the expected sickle-trait mutation,
      betaGlu6Val, but also a second, charge-neutral mutation, betaLeu68Phe. Analysis
      of the patient's hemoglobin revealed that the double-mutant protein, which we
      called "hemoglobin Jamaica Plain," had severely reduced oxygen affinity.
      Structural modeling suggested destabilization of the oxy conformation as a
      molecular mechanism for sickling in a heterozygote at an ambient partial pressure
      of oxygen.

PMID- 15470214
TI  - Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced
      refractory prostate cancer.
AB  - BACKGROUND: Mitoxantrone-based chemotherapy palliates pain without extending
      survival in men with progressive androgen-independent prostate cancer. We
      compared docetaxel plus estramustine with mitoxantrone plus prednisone in men
      with metastatic, hormone-independent prostate cancer. METHODS: We randomly
      assigned 770 men to one of two treatments, each given in 21-day cycles: 280 mg of
      estramustine three times daily on days 1 through 5, 60 mg of docetaxel per square
      meter of body-surface area on day 2, and 60 mg of dexamethasone in three divided
      doses before docetaxel, or 12 mg of mitoxantrone per square meter on day 1 plus 5
      mg of prednisone twice daily. The primary end point was overall survival;
      secondary end points were progression-free survival, objective response rates,
      and post-treatment declines of at least 50 percent in serum prostate-specific
      antigen (PSA) levels. RESULTS: Of 674 eligible patients, 338 were assigned to
      receive docetaxel and estramustine and 336 to receive mitoxantrone and
      prednisone. In an intention-to-treat analysis, the median overall survival was
      longer in the group given docetaxel and estramustine than in the group given
      mitoxantrone and prednisone (17.5 months vs. 15.6 months, P=0.02 by the log-rank
      test), and the corresponding hazard ratio for death was 0.80 (95 percent
      confidence interval, 0.67 to 0.97). The median time to progression was 6.3 months
      in the group given docetaxel and estramustine and 3.2 months in the group given
      mitoxantrone and prednisone (P<0.001 by the log-rank test). PSA declines of at
      least 50 percent occurred in 50 percent and 27 percent of patients, respectively
      (P<0.001), and objective tumor responses were observed in 17 percent and 11
      percent of patients with bidimensionally measurable disease, respectively
      (P=0.30). Grade 3 or 4 neutropenic fevers (P=0.01), nausea and vomiting
      (P<0.001), and cardiovascular events (P=0.001) were more common among patients
      receiving docetaxel and estramustine than among those receiving mitoxantrone and
      prednisone. Pain relief was similar in both groups. CONCLUSIONS: The improvement
      in median survival of nearly two months with docetaxel and estramustine, as
      compared with mitoxantrone and prednisone, provides support for this approach in
      men with metastatic, androgen-independent prostate cancer.

PMID- 15470217
TI  - Clinical practice. Aortic regurgitation.

PMID- 15470219
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Laboratory reference values.

PMID- 15470220
TI  - Stenting for carotid-artery stenosis.

PMID- 15470221
TI  - Prevention of hepatocellular carcinoma.

PMID- 15470222
TI  - Doctors and torture.

PMID- 15470223
TI  - Cetuximab in colon cancer.

PMID- 15470224
TI  - Hot-flash hypotension.

PMID- 15470225
TI  - Hemoglobin C disease.

PMID- 15470226
TI  - Comparative analyses reveal a complex history of molecular evolution for human
      MYH16.
AB  - We describe the pattern of molecular evolution at a sarcomeric myosin gene,
      MYH16, using more than 30,000 bp of exon and intron sequence data from the
      chimpanzee and human genome sequencing projects to evaluate the timing and
      consequences of a human lineage-specific frameshift deletion. We estimate the age
      of the deletion at approximately 5.3 MYA. This estimate is consistent with the
      time of human and chimpanzee divergence and is significantly older than the first
      appearance of the genus Homo in the fossil record. We also find conflicting
      estimates of nonsynonymous fixation rates (d(N)) across different regions of this
      gene, revealing a complex pattern inconsistent with a simple model of pseudogene
      evolution for human MYH16.

PMID- 15470227
TI  - Substitution rates in a new Silene latifolia sex-linked gene, SlssX/Y.
AB  - Dioecious white campion Silene latifolia has sex chromosomal sex determination,
      with homogametic (XX) females and heterogametic (XY) males. This species has
      become popular in studies of sex chromosome evolution. However, the lack of genes
      isolated from the X and Y chromosomes of this species is a major obstacle for
      such studies. Here, I report the isolation of a new sex-linked gene, Slss, with
      strong homology to spermidine synthase genes of other species. The new gene has
      homologous intact copies on the X and Y chromosomes (SlssX and SlssY,
      respectively). Synonymous divergence between the SlssX and SlssY genes is 4.7%,
      and nonsynonymous divergence is 1.4%. Isolation of a homologous gene from
      nondioecious S. vulgaris provided a root to the gene tree and allowed the
      estimation of the silent and replacement substitution rates along the SlssX and
      SlssY lineages. Interestingly, the Y-linked gene has higher synonymous and
      nonsynonymous substitution rates. The elevated synonymous rate in the SlssY gene,
      compared with SlssX, confirms our previous suggestion that the S. latifolia Y
      chromosome has a higher mutation rate, compared with the X chromosome. When
      differences in silent substitution rate are taken into account, the Y-linked gene
      still demonstrates significantly faster accumulation of nonsynonymous
      substitutions, which is consistent with the theoretical prediction of relaxed
      purifying selection in Y-linked genes, leading to the accumulation of
      nonsynonymous substitutions and genetic degeneration of the Y-linked genes.

PMID- 15470228
TI  - Measuring the fit of sequence data to phylogenetic model: allowing for missing
      data.
AB  - It is fundamentally important to assess the fit of data to model in phylogenetic
      and evolutionary studies. Phylogenetic methods using molecular sequences
      typically start with a multiple alignment. It is possible to measure the fit of
      data to model expectations of data, for example, via the likelihood-ratio (G)
      test or the X(2) test, if all sites in all sequences have an unambiguous residue.
      However, nearly all alignments of interest contain sites (columns of the
      alignment) with missing data, that is, ambiguous nucleotides, gaps, or
      unsequenced regions, which must presently be removed before using the above
      tests. Unfortunately, this is often either undesirable or impractical, as it will
      discard much of the data. Here, we show how iterative ML estimators may directly
      estimate the site-pattern probabilities for columns with missing data, given only
      standard i.i.d. assumptions. The optimization may use an EM or Newton algorithm,
      or any other hill-climbing approach. The resulting optimal likelihood under the
      unconstrained or multinomial model may be compared directly with the likelihood
      of the data coming from the model (a G statistic). Alternatively the modified
      observed and the expected frequencies of site patterns may be compared using a
      X(2) test. The distribution of such statistics is best assessed using appropriate
      simulations. The new method is applicable to models using codons or paired sites.
      The methods are also useful with Hadamard conjugations (spectral analysis) and
      are illustrated with these and with ML evolutionary models that allow site-rate
      variability.

PMID- 15470229
TI  - The structure of cell wall alpha-glucan from fission yeast.
AB  - Morphology and structural integrity of fungal cells depend on cell wall
      polysaccharides. The chemical structure and biosynthesis of two types of these
      polysaccharides, chitin and (1-->3)-beta-glucan, have been studied extensively,
      whereas little is known about alpha-glucan. Here we describe the chemical
      structure of alpha-glucan isolated from wild-type and mutant cell walls of the
      fission yeast Schizosaccharomyces pombe. Wild-type alpha-glucan was found to
      consist of a single population of linear glucose polymers, approximately 260
      residues in length. These glucose polymers were composed of two interconnected
      linear chains, each consisting of approximately 120 (1-->3)-linked alpha-d
      glucose residues and some (1-->4)-linked alpha-D-glucose residues at the reducing
      end. By contrast, alpha-glucan of an alpha-glucan synthase mutant with an
      aberrant cell morphology and reduced alpha-glucan levels consisted of a single
      chain only. We propose that alpha-glucan biosynthesis involves an ordered series
      of events, whereby two alpha-glucan chains are coupled to create mature cell wall
      alpha-glucan. This mature form of cell wall alpha-glucan is essential for fission
      yeast morphogenesis.

PMID- 15470230
TI  - Different acceptor specificities of two glucuronyltransferases involved in the
      biosynthesis of HNK-1 carbohydrate.
AB  - The biosynthesis of HNK-1 carbohydrate is mainly regulated by two
      glucuronyltransferases (GlcAT-P and GlcAT-S) and a sulfotransferase (HNK-1 ST).
      To determine how the two glucuronyltransferases are involved in the biosynthesis
      of the HNK-1 carbohydrate, we prepared soluble forms of GlcAT-P and GlcAT-S fused
      with the IgG-binding domain of protein A and then compared the enzymatic
      properties of the two enzymes. Both GlcAT-P and GlcAT-S transferred glucuronic
      acid (GlcA) not only to a glycoprotein acceptor, asialoorosomucoid (ASOR), but
      also to a glycolipid acceptor, paragloboside. The activity of GlcAT-P toward ASOR
      was enhanced fivefold in the presence of sphingomyelin, but there were no effects
      on that of GlcAT-S. The activities of the two enzymes toward paragloboside were
      only detected in the presence of phospholipids such as phosphatidylinositol.
      Kinetic analysis revealed that the K(m) value of GlcAT-P for ASOR was 10 times
      lower than that for paragloboside. Furthermore, acceptor specificity analysis
      involving various oligosaccarides revealed that GlcAT-P specifically recognized N
      acetyllactosamine (Galbeta1-4GlcNAc) at the nonreducing terminals of acceptor
      substrates. In contrast, GlcAT-S recognized not only the terminal Galbeta1
      4GlcNAc structure but also the Galbeta1-3GlcNAc structure and showed the highest
      activity toward triantennary N-linked oligosaccharides. GlcAT-P transferred GlcA
      to NCAM about twice as much as to ASOR, whereas GlcAT-S did not show any activity
      toward NCAM. These lines of evidence indicate that these two enzymes have
      significantly different acceptor specificities, suggesting that they may
      synthesize functionally and structurally different HNK-1 carbohydrates in the
      nervous system.

PMID- 15470231
TI  - IL-1 and TNF antagonists prevent inhibition of fracture healing by ethanol in
      rats.
AB  - We tested the hypothesis that combined administration of IL-1 and TNF antagonists
      would protect fracture healing from inhibition by chronic ethanol exposure. Adult
      male rats were fed a liquid diet +/- ethanol (CON and ETOH) by intragastric
      infusion for three weeks prior to and three weeks after creation of an externally
      fixated tibial fracture. Beginning the day of fracture, one-half of each dietary
      group received 2.0 mg/kg/day IL-1ra and 2.0 mg/kg/2-days sTNFR1 (CON + ANTAG and
      ETOH + ANTAG), while all other animals received vehicle alone (CON + VEH and ETOH
      + VEH). Scoring of ex vivo radiographs and analysis by pQCT revealed a
      significantly lower incidence of bridging and reduced total mineral content in
      the ETOH + VEH group compared to all other groups. These results support, for the
      first time, the hypothesis that IL-1 and TNF antagonists are capable of
      protecting fracture healing from the inhibition associated with chronic ethanol
      consumption.

PMID- 15470232
TI  - Organophosphorus insecticides induce airway hyperreactivity by decreasing
      neuronal M2 muscarinic receptor function independent of acetylcholinesterase
      inhibition.
AB  - We previously demonstrated that the organophosphorus (OP) insecticide
      chlorpyrifos potentiates vagally induced bronchoconstriction independent of
      acetylcholinesterase (AChE) inhibition by decreasing the function of neuronal M2
      muscarinic receptors that normally inhibit acetylcholine release from
      parasympathetic nerves supplying airway smooth muscle. However, it has been
      reported that different OPs may not affect muscarinic receptors equally. To
      determine if the effects of chlorpyrifos on airway hyperreactivity can be
      generalized to other OPs, we tested whether parathion and diazinon also inhibit
      neuronal M2 receptor function resulting in airway hyperreactivity. In control
      animals, the M2 agonist pilocarpine inhibits vagally induced bronchoconstriction
      in a dose-related manner. Treatment of guinea pigs with either parathion (1-10
      mg/kg, sc) or diazinon (0.75-75 mg/kg, sc) shifted pilocarpine dose-response
      curves significantly to the right, indicating loss of neuronal M2 receptor
      function. These OP treatments also significantly potentiated vagally induced
      bronchoconstriction. Treatments that did not decrease M2 receptor function
      (parathion at 0.1 mg/kg, sc, or the non-OP insecticide permethrin at 150 mg/kg,
      sc) also did not cause airway hyperreactivity. None of the OP treatments altered
      bronchoconstriction induced by iv acetylcholine or methacholine in vagotomized
      guinea pigs, suggesting that OP-induced airway hyperreactivity is not due to
      altered function of muscarinic receptors on airway smooth muscle or to AChE
      inhibition. AChE assays of lung, blood, and brain confirmed that parathion and
      diazinon decreased M2 function at concentrations that did not inhibit AChE. These
      data suggest that multiple diethyl phosphorothionate OPs cause airway
      hyperreactivity via a common mechanism of M2 receptor dysfunction independent of
      AChE inhibition.

PMID- 15470233
TI  - Pharmacokinetics of perfluorooctanoate in cynomolgus monkeys.
AB  - The pharmacokinetics of perfluorooctanoate (PFOA) in cynomolgus monkeys were
      studied in a six-month oral capsule dosing study of ammonium perfluorooctanoate
      (APFO) and in a single-dose iv study. In the oral study, samples of serum, urine,
      and feces were collected every two weeks from monkeys given daily doses of either
      0, 3, 10, or 20 mg APFO/kg. Steady-state was reached within four weeks in serum,
      urine, and feces. Serum PFOA followed first-order elimination kinetics after the
      last dose, with a half-life of approximately 20 days. Urine was the primary
      elimination route. Mean serum PFOA concentrations at steady state in the 3, 10,
      and 20 mg/kg-day dose groups, respectively, were 81, 99, and 156 microg/ml in
      serum; 53, 166, and 181 microg/ml in urine; and, 7, 28, and 50 microg/g in feces.
      Mean liver concentrations reached 16, 14, and 50 microg/g in the 3, 10, and 20
      mg/kg groups, respectively. In the iv study, three monkeys per sex were given a
      single dose of 10 mg/kg potassium PFOA. Samples were collected through 123 days.
      The terminal half-life of PFOA in serum was 13.6, 13.7, and 35.3 days in the
      three male monkeys and 26.8, 29.3, and 41.7 days in the three females. Volume of
      distribution at steady state was 181 +/- 12 and 198 +/- 69 ml/kg for males and
      females, respectively. Based on the result of both the oral and iv studies, the
      elimination half-life is approximately 14-42 days, and urine is the primary route
      of excretion.

PMID- 15470234
TI  - Glutathione-dependent reduction of arsenate in human erythrocytes--a process
      independent of purine nucleoside phosphorylase.
AB  - Reduction of arsenate (AsV) to the more toxic arsenite (AsIII) is toxicologically
      important, yet its mechanism is unknown. To clarify this, AsV reduction was
      investigated in human red blood cells (RBC), as they possess a simple metabolism.
      RBC were incubated with AsV in gluconate buffer, and the formed AsIII was
      quantified by high performance liquid chromatography-hydride generation-atomic
      fluorescence spectrometry (HPLC-HG-AFS). The observations are compatible with the
      following conclusions. (1) Human RBC reduce AsV intracellularly, because 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, inhibitor of the chloride
      bicarbonate exchanger, which also mediates phosphate and AsV uptake), as well as
      chloride and phosphate, countered AsIII formation. (2) Purine nucleoside
      phosphorylase (PNP), whose AsV reductase activity has been directly demonstrated,
      cannot be a physiologically relevant AsV reductase, because its inhibitor (BCX
      1777) failed to decrease the basal erythrocytic AsV reduction, although it
      prevented the increase in AsIII formation caused by artificial activation of PNP
      with inosine and dithiothreitol. (3) The basal (PNP-independent) AsV reduction
      requires glutathione (GSH), because the GSH depletor diethylmaleate strongly
      diminished AsIII formation. (4) The erythrocytic AsV reduction apparently depends
      on NAD(P) supply, because oxidants of NAD(P)H (i.e., pyruvate, ferricyanide,
      methylene blue, nitrite, tert-butylhydroperoxide, dehydroascorbate, 4
      dimethylaminophenol) enhanced AsIII formation from AsV. The oxidant-stimulated
      AsV reduction is PNP-independent, because BCX-1777 failed to affect it, but is
      GSH-dependent, because diethylmaleate impaired it. (5) Pyruvate-induced glucose
      depletion, which causes NAD enrichment in the erythrocytes at the expense of
      NADH, enhanced AsV reduction. This suggests that the erythrocytic AsV reduction
      requires both NAD supply and operation of the lower part of the glycolytic
      pathway starting from glyceraldehyde-3-phosphate dehydrogenase (GAPDH) that,
      unlike the upper part, remains fed with substrates originating from the
      degradation of 2,3-bisphosphoglycerate in RBC depleted of glucose by pyruvate.
      (6) Fluoride, which arrests glycolysis at enolase and thus prevents NAD
      formation, inhibited AsV reduction in glucose-sufficient RBC, but increased it in
      glucose-deficient (NAD-enriched) cells, suggesting that the section of glycolysis
      coupled to AsV reduction lies between GAPDH and enolase. In conclusion, besides
      the artificial PNP-dependent AsV reduction, human RBC contain a PNP-independent
      AsV-reducing mechanism. This appears to require the supply of GSH, NAD, and
      substrate to one or more of the glycolytic enzymes localized between GAPDH and
      enolase.

PMID- 15470235
TI  - Role of phagocytosis in the virulence of Cryptococcus neoformans.

PMID- 15470236
TI  - Transcriptional response of Candida albicans upon internalization by macrophages.
AB  - The opportunistic fungal pathogen Candida albicans is both a benign gut commensal
      and a frequently fatal systemic pathogen. The interaction of C. albicans with the
      host's innate immune system is the primary factor in this balance; defects in
      innate immunity predispose the patient to disseminated candidiasis. Because of
      the central importance of phagocytic cells in defense against fungal infections,
      we have investigated the response of C. albicans to phagocytosis by mammalian
      macrophages using genomic transcript profiling. This analysis reveals a dramatic
      reprogramming of transcription in C. albicans that occurs in two successive
      steps. In the early phase cells shift to a starvation mode, including
      gluconeogenic growth, activation of fatty acid degradation, and downregulation of
      translation. In a later phase, as hyphal growth enables C. albicans to escape
      from the macrophage, cells quickly resume glycolytic growth. In addition, there
      is a substantial nonmetabolic response imbedded in the early phase, including
      machinery for DNA damage repair, oxidative stress responses, peptide uptake
      systems, and arginine biosynthesis. Further, a surprising percentage of the genes
      that respond specifically to macrophage contact have no known homologs,
      suggesting that the organism has undergone substantial evolutionary adaptations
      to the commensal or pathogen lifestyle. This transcriptional reprogramming is
      almost wholly absent in the related, but nonpathogenic, yeast Saccharomyces
      cerevisiae, suggesting that these large-scale and coordinated changes contribute
      significantly to the ability of this organism to survive and cause disease in
      vivo.

PMID- 15470237
TI  - Introns and splicing elements of five diverse fungi.
AB  - Genomic sequences and expressed sequence tag data for a diverse group of fungi
      (Saccharomyces cerevisiae, Schizosaccharomyces pombe, Aspergillus nidulans,
      Neurospora crassa, and Cryptococcus neoformans) provided the opportunity to
      accurately characterize conserved intronic elements. An examination of large
      intron data sets revealed that fungal introns in general are short, that 98% or
      more of them belong to the canonical splice site (ss) class (5'GU...AG3'), and
      that they have polypyrimidine tracts predominantly in the region between the 5'
      ss and the branch point. Information content is high in the 5' ss, branch site,
      and 3' ss regions of the introns but low in the exon regions adjacent to the
      introns in the fungi examined. The two yeasts have broader intron length ranges
      and correspondingly higher intron information content than the other fungi.
      Generally, as intron length increases in the fungi, so does intron information
      content. Homologs of U2AF spliceosomal proteins were found in all species except
      for S. cerevisiae, suggesting a nonconventional role for U2AF in the absence of
      canonical polypyrimidine tracts in the majority of introns. Our observations
      imply that splicing in fungi may be different from that in vertebrates and may
      require additional proteins that interact with polypyrimidine tracts upstream of
      the branch point. Theoretical protein homologs for Nam8p and TIA-1, two proteins
      that require U-rich regions upstream of the branch point to function, were found.
      There appear to be sufficient differences between S. cerevisiae and S. pombe
      introns and the introns of two filamentous members of the Ascomycota and one
      member of the Basidiomycota to warrant the development of new model organisms for
      studying the splicing mechanisms of fungi.

PMID- 15470238
TI  - Transcriptional transitions during Dictyostelium spore germination.
AB  - Many protozoa form spores in response to adversity; therefore, spore germination
      is a key process in their life cycle. Dictyostelium discoideum sporulates in
      response to starvation following a developmental program. Germination is
      characterized by two visible changes, spore swelling and the emergence of amoeba
      from the spore capsule. Several studies have indicated that an additional process
      termed spore activation is also required, but the physiological changes that
      characterize the three phases are largely uncharacterized. We used microarrays to
      monitor global transcriptional transitions as a surrogate measure of the
      physiological changes that occur during germination. Using two independent
      methods to induce germination, we identified changes in mRNA levels that
      characterized the germination process rather than changes that resulted from the
      induction method. We found that germination is characterized by three
      transitions. The first transition occurs during activation, while the spores
      appear dormant, the largest transition occurs when swelling begins, and the third
      transition occurs when emergence begins. These findings indicate that activation
      and swelling are not passive occurrences, such as dilution of inhibitors or spore
      rehydration, but are active processes that are accompanied by dramatic events in
      mRNA degradation and de novo transcription. These findings confirm and extend
      earlier reports that genes such as celA are regulated during spore germination.
      We also found by mutation analysis that the unconventional myosin gene myoI,
      which is induced during early germination, plays roles in the maintenance of
      dormancy and in spore swelling. This finding suggests that some of the observed
      transcriptional changes are required for spore germination.

PMID- 15470239
TI  - Msn2- and Msn4-like transcription factors play no obvious roles in the stress
      responses of the fungal pathogen Candida albicans.
AB  - In Saccharomyces cerevisiae, the (C2H2)2 zinc finger transcription factors Msn2
      and Msn4 play central roles in responses to a range of stresses by activating
      gene transcription via the stress response element (STRE; CCCCT). The pathogen
      Candida albicans displays stress responses that are thought to help it survive
      adverse environmental conditions encountered within its human host. However,
      these responses differ from those in S. cerevisiae, and hence we predicted that
      the roles of Msn2- and Msn4-like proteins might have been functionally reassigned
      in C. albicans. C. albicans has two such proteins: CaMsn4 and Mnl1 (for Msn2- and
      Msn4-like). CaMSN4, but not MNL1, weakly complemented the inability of an S.
      cerevisiae msn2 msn4 mutant to activate a STRE-lacZ reporter. Also, the
      disruption of CaMsn4 and Mnl1 had no discernible effect upon the resistance of C.
      albicans to heat, osmotic, ethanol, nutrient, oxidative, or heavy-metal stress or
      upon the stress-activated transcriptome in C. albicans. Furthermore, although
      Cap1-dependent activation of a Yap response element-luciferase reporter was
      observed, a STRE reporter was not activated in response to stresses in C.
      albicans. Ectopic expression of CaMsn4 or Mnl1 did not affect the cellular or
      molecular responses of C. albicans to stress. Under the conditions tested, the
      putative activation and DNA binding domains of CaMsn4 did not appear to be
      functional. These data suggest that CaMsn4 and Mnl1 do not contribute
      significantly to stress responses in C. albicans. The data are consistent with
      the idea that stress signaling in this fungus has diverged significantly from
      that in budding yeast.

PMID- 15470240
TI  - Schizosaccharomyces pombe Pmr1p is essential for cell wall integrity and is
      required for polarized cell growth and cytokinesis.
AB  - The cps5-138 fission yeast mutant shows an abnormal lemon-like morphology at 28
      degrees C in minimal medium and a lethal thermosensitive phenotype at 37 degrees
      C. Cell growth is completely inhibited at 28 degrees C in a Ca2+-free medium, in
      which the wild type is capable of growing normally. Under these conditions, actin
      patches become randomly distributed throughout the cell, and defects in septum
      formation and subsequent cytokinesis appear. The mutant cell is hypersensitive to
      the cell wall-digesting enzymatic complex Novozym234 even under permissive
      conditions. The gene SPBC31E1.02c, which complements all the mutant phenotypes
      described above, was cloned and codes for the Ca2+-ATPase homologue Pmr1p. The
      gene is not essential under optimal growth conditions but is required under
      conditions of low Ca2+ (<0.1 mM) or high temperature (>35 degrees C). The green
      fluorescent protein-tagged Cps5 proteins, which are expressed under physiological
      conditions (an integrated single copy with its own promoter in the cps5Delta
      strain), display a localization pattern typical of endoplasmic reticulum
      proteins. Biochemical analyses show that 1,3-beta-D-glucan synthase activity in
      the mutant is decreased to nearly half that of the wild type and that the mutant
      cell wall contains no detectable galactomannan when the cells are exposed to a
      Ca2+-free medium. The mutant acid phosphatase has an increased electrophoretic
      mobility, suggesting that incomplete protein glycosylation takes place in the
      mutant cells. These results indicate that S. pombe Pmr1p is essential for the
      maintenance of cell wall integrity and cytokinesis, possibly by allowing protein
      glycosylation and the polarized actin distribution to take place normally.
      Disruption and complementation analyses suggest that Pmr1p shares its function
      with a vacuolar Ca2+-ATPase homologue, Pmc1p (SPAPB2B4.04c), to prevent lethal
      activation of calcineurin for cell growth.

PMID- 15470241
TI  - Epigenetic control of chromosome breakage at the 5' end of Paramecium tetraurelia
      gene A.
AB  - Macronuclei and micronuclei of ciliates have related genomes, with macronuclei
      developing from zygotic micronuclei through programmed DNA rearrangements. While
      Paramecium tetraurelia wild-type strain 51 and mutant strain d48 have the same
      micronuclear genome, qualitative differences between their macronuclear genomes
      have been described, demonstrating that programmed DNA rearrangements could be
      epigenetically controlled in ciliates. Macronuclear chromosomes end downstream of
      gene A (A51 Mac ends) and at the 5' end of gene A (Ad48 Mac ends) in strains 51
      and d48, respectively. To gain further insight into the process of chromosome end
      formation, we performed an extensive analysis of locus A rearrangement in strains
      d48 and 51, in strain d12, which harbors a gene A deletion, and in interstrain
      cross progeny. We show that (i) allele Ad12 harbors a deletion of >16 kb, (ii)
      A51 Mac ends distribute over four rather than three DNA regions, (iii) strains
      d48 and 51 display only quantitative differences (rare Ad48 and A51 Mac ends do
      form in strains 51 and d48, respectively), (iv) the level of A51 Mac ends is
      severalfold enhanced in d12- and d48-derived progeny, and (v) this level
      inversely correlates with the level of Ad48 Mac ends in the d48 parent. Together,
      these data lead to a model in which the formation of Ad48 Mac ends is
      epigenetically controlled by a d48 factor(s). We propose that the d48 factor(s)
      may be derived from RNA molecules transcribed from the Ad48 Mac ends and
      encompassing the truncated A gene and telomeric repeats.

PMID- 15470242
TI  - Integration of stress responses: modulation of calcineurin signaling in
      Saccharomyces cerevisiae by protein kinase A.
AB  - Calcineurin is a Ca2+/calmodulin-dependent protein phosphatase required for
      Saccharomyces cerevisiae to adapt to a variety of environmental stresses. Once
      activated, calcineurin dephosphorylates the Zn-finger transcription factor
      Crz1p/Tcn1p, causing it to accumulate in the nucleus where it activates gene
      expression. Here we show that cyclic AMP-dependent protein kinase A (PKA)
      phosphorylates and negatively regulates Crz1p activity by inhibiting its nuclear
      import. Activation of PKA in vivo decreases Crz1p-dependent transcription. PKA
      phosphorylates Crz1p in vitro, and we identify specific residues required for
      this phosphorylation, all of which reside in or adjacent to the nuclear
      localization signal. Mutation of these residues to alanine results in increased
      nuclear import of Crz1p and results in higher levels of both basal and Ca2+
      induced Crz1p transcriptional activity. PKA regulates the general stress response
      in yeast and coordinates this response with nutrient availability. In contrast,
      calcineurin regulates the cellular response to a restricted set of environmental
      insults. Thus, these studies identify a specific biochemical mechanism through
      which the activities of multiple stress-activated signaling pathways are
      integrated in vivo.

PMID- 15470243
TI  - Inner kinetochore of the pathogenic yeast Candida glabrata.
AB  - The human pathogenic yeast Candida glabrata is the second most common Candida
      pathogen after Candida albicans, causing both bloodstream and mucosal infections.
      The centromere (CEN) DNA of C. glabrata (CgCEN), although structurally very
      similar to that of Saccharomyces cerevisiae, is not functional in S. cerevisiae.
      To further examine the structure of the C. glabrata inner kinetochore, we
      isolated several C. glabrata homologs of S. cerevisiae inner kinetochore protein
      genes, namely, genes for components of the CBF3 complex (Ndc10p, Cep3p, and
      Ctf13p) and genes for the proteins Mif2p and Cse4p. The amino acid sequence
      identities of these proteins were 32 to 49% relative to S. cerevisiae. CgNDC10,
      CgCEP3, and CgCTF13 are required for growth in C. glabrata and are specifically
      found at CgCEN, as demonstrated by chromatin immunoprecipitation experiments.
      Cross-complementation experiments revealed that the isolated genes, with the
      exception of CgCSE4, are species specific and cannot functionally substitute for
      the corresponding genes in S. cerevisiae deletion strains. Likewise, the S.
      cerevisiae CBF3 genes NDC10, CEP3, and CTF13 cannot functionally replace their
      homologs in C. glabrata CBF3 deletion strains. Two-hybrid analysis revealed
      several interactions between these proteins, all of which were previously
      reported for the inner kinetochore proteins of S. cerevisiae. Our findings
      indicate that although many of the inner kinetochore components have evolved
      considerably between the two closely related species, the organization of the C.
      glabrata inner kinetochore is similar to that in S. cerevisiae.

PMID- 15470245
TI  - Gene replacement of fructose-1,6-bisphosphate aldolase supports the hypothesis of
      a single photosynthetic ancestor of chromalveolates.
AB  - Plastids (photosynthetic organelles of plants and algae) are known to have spread
      between eukaryotic lineages by secondary endosymbiosis, that is, by the uptake of
      a eukaryotic alga by another eukaryote. But the number of times this has taken
      place is controversial. This is particularly so in the case of eukaryotes with
      plastids derived from red algae, which are numerous and diverse. Despite their
      diversity, it has been suggested that all these eukaryotes share a recent common
      ancestor and that their plastids originated in a single endosymbiosis, the so
      called "chromalveolate hypothesis." Here we describe a novel molecular character
      that supports the chromalveolate hypothesis. Fructose-1,6-bisphosphate aldolase
      (FBA) is a glycolytic and Calvin cycle enzyme that exists as two nonhomologous
      types, class I and class II. Red algal plastid-targeted FBA is a class I enzyme
      related to homologues from plants and green algae, and it would be predicted that
      the plastid-targeted FBA from algae with red algal secondary endosymbionts should
      be related to this class I enzyme. However, we show that plastid-targeted FBA of
      heterokonts, cryptomonads, haptophytes, and dinoflagellates (all photosynthetic
      chromalveolates) are class II plastid-targeted enzymes, completely unlike those
      of red algal plastids. The chromalveolate enzymes form a strongly supported group
      in FBA phylogeny, and their common possession of this unexpected plastid
      characteristic provides new evidence for their close relationship and a common
      origin for their plastids.

PMID- 15470244
TI  - Pmt-mediated O mannosylation stabilizes an essential component of the secretory
      apparatus, Sec20p, in Candida albicans.
AB  - Sec20p is an essential endoplasmic reticulum (ER) membrane protein in yeasts,
      functioning as a tSNARE component in retrograde vesicle traffic. We show that
      Sec20p in the human fungal pathogen Candida albicans is extensively O
      mannosylated by protein mannosyltransferases (Pmt proteins). Surprisingly, Sec20p
      occurs at wild-type levels in a pmt6 mutant but at very low levels in pmt1 and
      pmt4 mutants and also after replacement of specific Ser/Thr residues in the
      lumenal domain of Sec20p. Pulse-chase experiments revealed rapid degradation of
      unmodified Sec20p (38.6 kDa) following its biosynthesis, while the stable O
      glycosylated form (50 kDa) was not formed in a pmt1 mutant. These results suggest
      a novel function of O mannosylation in eukaryotes, in that modification by
      specific Pmt proteins will prevent degradation of ER-resident membrane proteins
      via ER-associated degradation or a proteasome-independent pathway.

PMID- 15470246
TI  - A cell number counting factor regulates Akt/protein kinase B to regulate
      Dictyostelium discoideum group size.
AB  - Little is known about how individual cells can organize themselves to form
      structures of a given size. During development, Dictyostelium discoideum
      aggregates in dendritic streams and forms groups of approximately 20,000 cells.
      D. discoideum regulates group size by secreting and simultaneously sensing a
      multiprotein complex called counting factor (CF). If there are too many cells in
      a stream, the associated high concentration of CF will decrease cell-cell
      adhesion and increase cell motility, causing aggregation streams to break up. The
      pulses of cyclic AMP (cAMP) that mediate aggregation cause a transient
      translocation of Akt/protein kinase B (Akt/PKB) to the leading edge of the plasma
      membrane and a concomitant activation of the kinase activity, which in turn
      stimulates motility. We found that countin- cells (which lack bioactive CF) and
      wild-type cells starved in the presence of anticountin antibodies (which block CF
      activity) showed a decreased level of cAMP-stimulated Akt/PKB membrane
      translocation and kinase activity compared to parental wild-type cells.
      Recombinant countin has the bioactivity of CF, and a 1-min treatment of cells
      with recombinant countin potentiated Akt/PKB translocation to membranes and
      Akt/PKB activity. Western blotting of total cell lysates indicated that countin
      does not affect the total level of Akt/PKB. Fluorescence microscopy of cells
      expressing an Akt/PKB pleckstrin homology domain-green fluorescent protein (PH
      GFP) fusion protein indicated that recombinant countin and anti-countin
      antibodies do not obviously alter the distribution of Akt/PKB PH-GFP when it
      translocates to the membrane. Our data indicate that CF increases motility by
      potentiating the cAMP-stimulated activation and translocation of Akt/PKB.

PMID- 15470247
TI  - Presence of a poly(A) binding protein and two proteins with cell cycle-dependent
      phosphorylation in Crithidia fasciculata mRNA cycling sequence binding protein
      II.
AB  - Crithidia fasciculata cycling sequence binding proteins (CSBP) have been shown to
      bind with high specificity to sequence elements present in several mRNAs that
      accumulate periodically during the cell cycle. The first described CSBP has
      subunits of 35.6 (CSBPA) and 42 kDa (CSBPB). A second distinct binding protein
      termed CSBP II has been purified from CSBPA null mutant cells, lacking both CSBPA
      and CSBPB proteins, and contains three major polypeptides with predicted
      molecular masses of 63, 44.5, and 33 kDa. Polypeptides of identical size were
      radiolabeled in UV cross-linking assays performed with purified CSBP II and 32P
      labeled RNA probes containing six copies of the cycling sequence. The CSBP II
      binding activity was found to cycle in parallel with target mRNA levels during
      progression through the cell cycle. We have cloned genes encoding these three
      CSBP II proteins, termed RBP63, RBP45, and RBP33, and characterized their binding
      properties. The RBP63 protein is a member of the poly(A) binding protein family.
      Homologs of RBP45 and RBP33 proteins were found only among the kinetoplastids.
      Both RBP45 and RBP33 proteins and their homologs have a conserved carboxy
      terminal half that contains a PSP1-like domain. All three CSBP II proteins show
      specificity for binding the wild-type cycling sequence in vitro. RBP45 and RBP33
      are phosphoproteins, and RBP45 has been found to bind in vivo specifically to
      target mRNA containing cycling sequences. The levels of phosphorylation of both
      RBP45 and RBP33 were found to cycle during the cell cycle.

PMID- 15470248
TI  - Nucleus-encoded genes for plastid-targeted proteins in Helicosporidium:
      functional diversity of a cryptic plastid in a parasitic alga.
AB  - Plastids are the organelles of plants and algae that house photosynthesis and
      many other biochemical pathways. Plastids contain a small genome, but most of
      their proteins are encoded in the nucleus and posttranslationally targeted to the
      organelle. When plants and algae lose photosynthesis, they virtually always
      retain a highly reduced "cryptic" plastid. Cryptic plastids are known to exist in
      many organisms, although their metabolic functions are seldom understood. The
      best-studied example of a cryptic plastid is from the intracellular malaria
      parasite, Plasmodium, which has retained a plastid for the biosynthesis of fatty
      acids, isoprenoids, and heme by the use of plastid-targeted enzymes. To study a
      completely independent transformation of a photosynthetic plastid to a cryptic
      plastid in another alga-turned-parasite, we conducted an expressed sequence tag
      (EST) survey of Helicosporidium. This parasite has recently been recognized as a
      highly derived green alga. Based on phylogenetic relationships to other plastid
      homologues and the presence of N-terminal transit peptides, we have identified 20
      putatively plastid-targeted enzymes that are involved in a wide variety of
      metabolic pathways. Overall, the metabolic diversity of the Helicosporidium
      cryptic plastid exceeds that of the Plasmodium plastid, as it includes
      representatives of most of the pathways known to operate in the Plasmodium
      plastid as well as many others. In particular, several amino acid biosynthetic
      pathways have been retained, including the leucine biosynthesis pathway, which
      was only recently recognized in plant plastids. These two parasites represent
      different evolutionary trajectories in plastid metabolic adaptation.

PMID- 15470250
TI  - A beta-tubulin mutation selectively uncouples nuclear division and cytokinesis in
      Tetrahymena thermophila.
AB  - The ciliated protozoan Tetrahymena thermophila contains two distinct nuclei
      within a single cell-the mitotic micronucleus and the amitotic macronucleus.
      Although microtubules are required for proper division of both nuclei,
      macronuclear chromosomes lack centromeres and the role of microtubules in
      macronuclear division has not been established. Here we describe nuclear division
      defects in cells expressing a mutant beta-tubulin allele that confers
      hypersensitivity to the microtubule-stabilizing drug paclitaxel. Macronuclear
      division is profoundly affected by the btu1-1 (K350M) mutation, producing cells
      with widely variable DNA contents, including cells that lack macronuclei
      entirely. Protein expressed by the btu1-1 allele is dominant over wild-type
      protein expressed by the BTU2 locus. Normal macronuclear division is restored
      when the btu1-1 allele is inactivated by targeted disruption or expressed as a
      truncated protein. Immunofluorescence studies reveal elongated microtubular
      structures that surround macronuclei that fail to migrate to the cleavage
      furrows. In contrast, other cytoplasmic microtubule-dependent processes, such as
      cytokinesis, cortical patterning, and oral apparatus assembly, appear to be
      unaffected in the mutant. Micronuclear division is also perturbed in the K350M
      mutant, producing nuclei with elongated early-anaphase spindle configurations
      that persist well after the initiation of cytokinesis. The K350M mutation affects
      tubulin dynamics, as the macronuclear division defect is exacerbated by three
      treatments that promote microtubule polymerization: (i) elevated temperatures,
      (ii) sublethal concentrations of paclitaxel, and (iii) high concentrations of
      dimethyl sulfoxide. Inhibition of phosphatidylinositol 3-kinase (PI 3-kinase)
      with 3-methyladenine or wortmannin also induces amacronucleate cell formation in
      a btu1-1-dependent manner. Conversely, the myosin light chain kinase inhibitor ML
      7 has no effect on nuclear division in the btu1-1 mutant strain. These findings
      provide new insights into microtubule dynamics and link the evolutionarily
      conserved PI 3-kinase signaling pathway to nuclear migration and/or division in
      Tetrahymena.

PMID- 15470249
TI  - TbDSS-1, an essential Trypanosoma brucei exoribonuclease homolog that has
      pleiotropic effects on mitochondrial RNA metabolism.
AB  - Mitochondrial gene expression in trypanosomes is controlled primarily at the
      levels of RNA processing and RNA stability. This regulation undoubtedly involves
      numerous ribonucleases. Here we characterize the Trypanosoma brucei homolog of
      the yeast DSS-1 mitochondrial exoribonuclease, which we term TbDSS-1. Biochemical
      fractionation indicates that TbDSS-1 is mitochondrially localized, as predicted
      by its N-terminal sequence. In contrast to its yeast homolog, TbDSS-1 does not
      appear to be associated with mitochondrial ribosomes. Targeted downregulation of
      TbDSS-1 by RNA interference in procyclic-form T. brucei results in a severe
      growth defect. In addition, TbDSS-1 depletion leads to a decrease in the levels
      of never edited cytochrome oxidase subunit I (COI) mRNA and both unedited and
      edited COIII mRNAs, indicating this enzyme functions in the control of
      mitochondrial RNA abundance. We also observe a considerable reduction in the
      level of edited apocytochrome b (CYb) mRNA and a corresponding increase in
      unedited CYb mRNA, suggesting that TbDSS-1 functions, either directly or
      indirectly, in the control of RNA editing. The abundance of both gCYb[560] and
      gA6[149] guide RNAs is reduced upon TbDSS-1 depletion, although the reduction in
      gCYb[560] is much more dramatic. The significant reduction in gCYb levels could
      potentially account for the observed decrease in CYb RNA editing. Western blot
      analyses of mitochondrial RNA editing and stability factors indicate that the
      perturbations of RNA levels observed in TbDSS-1 knock-downs do not result from
      secondary effects on other mitochondrial proteins. In all, these data demonstrate
      that TbDSS-1 is an essential protein that plays a role in mitochondrial RNA
      stability and RNA editing.

PMID- 15470252
TI  - RNA polymerase II localizes in Tetrahymena thermophila meiotic micronuclei when
      micronuclear transcription associated with genome rearrangement occurs.
AB  - The germ line micronucleus in Tetrahymena thermophila is transcriptionally silent
      in vegetatively growing cells. However, micronuclear transcription has been
      observed in the early ("crescent") stages of the sexual process, conjugation.
      This transcription is proposed to play a central role in identifying sites for
      subsequent genome rearrangements that accompany development of the somatic
      macronucleus from the micronucleus. RPB3 (cnjC), a gene encoding a protein
      homologous to the third largest subunit of RNA polymerase II (RNAP II), was
      previously reported to be expressed specifically during conjugation, suggesting a
      role in micronucleus-specific transcription. Rpb3p localized in the micronucleus
      only during the meiotic prophase, when micronuclear transcription occurs, and its
      intranuclear distribution is strikingly similar to that for previously described
      sites of micronuclear RNA synthesis. By contrast, Rpc5p, the homologous subunit
      shared by RNAPs I and III, was not detectable in the micronucleus at any stage of
      the life cycle. However, Rpb3p is not specific to the transcribing micronucleus.
      Like Rpc5p, it also localizes to macronuclei in all stages of the life cycle.
      Rpb3p is encoded by a unique, essential gene in Tetrahymena. Thus, RNAP II is
      associated with both somatic transcription and crescent transcription and
      probably has an important role in genome rearrangement.

PMID- 15470251
TI  - Linkage between mitochondrial hypovirulence and viral hypovirulence in the
      chestnut blight fungus revealed by cDNA microarray analysis.
AB  - The phenomenon of transmissible hypovirulence (virulence attenuation) associated
      with biological control of natural populations of the chestnut blight fungus
      Cryphonectria parasitica can be experimentally reproduced by infection with
      hypovirus cDNA clones (viral hypovirulence) or by mutation of mitochondrial DNA
      (mtDNA) in the absence of virus infection (mitochondrial hypovirulence). We now
      report the use of an established C. parasitica cDNA microarray to monitor nuclear
      transcriptional responses to an mtDNA mutation of C. parasitica strain EP155,
      designated EP155/mit2, which was previously shown to induce elevated alternative
      oxidase activity and hypovirulence (C. B. Monterio-Vitorello, J. A. Bell, D. W.
      Fulbright, and H. A. Bertrand, Proc. Natl. Acad. Sci. USA 92:5935-5939, 1995).
      Approximately 10% of the 2,200 genes represented on the microarray exhibited
      altered transcript accumulation as a result of the mit2 mtDNA mutation. While
      genes involved in mitochondrial function were clearly represented in the
      EP155/mit2-responsive gene list, direct parallels to the well-characterized
      Saccharomyces cerevisiae retrograde response to mitochondrial dysfunction were
      not observed. Remarkably, 47% of the genes that were differentially expressed
      following the infection of strain EP155 by the prototypic hypovirus CHV1-EP713
      had similarly changed transcript accumulation in the virus-free EP155/mit2
      mutant. These results establish a linkage between viral and mitochondrial
      hypovirulence and raise questions regarding the relationship between hypovirus
      infection and mitochondrial dysfunction. The combined set of transcriptional
      profile data provides a foundation for future studies on mitochondrion-to-nucleus
      communications in the context of hypovirus infection and senescence associated
      with mitochondrial dysfunction in filamentous fungi.

PMID- 15470253
TI  - Control of cell type proportioning in Dictyostelium discoideum by differentiation
      inducing factor as determined by in situ hybridization.
AB  - We have determined the proportions of the prespore and prestalk regions in
      Dictyostelium discoideum slugs by in situ hybridization with a large number of
      prespore- and prestalk-specific genes. Microarrays were used to discover genes
      expressed in a cell type-specific manner. Fifty-four prespore-specific genes were
      verified by in situ hybridization, including 18 that had been previously shown to
      be cell type specific. The 36 new genes more than doubles the number of available
      prespore markers. At the slug stage, the prespore genes hybridized to cells
      uniformly in the posterior 80% of wild-type slugs but hybridized to the posterior
      90% of slugs lacking the secreted alkylphenone differentiation-inducing factor 1
      (DIF-1). There was a compensatory twofold decrease in prestalk cells in DIF-less
      slugs. Removal of prespore cells resulted in cell type conversion in both wild
      type and DIF-less anterior fragments. Thus, DIF-1 appears to act in concert with
      other processes to establish cell type proportions.

PMID- 15470254
TI  - Identification of Cryptococcus neoformans temperature-regulated genes with a
      genomic-DNA microarray.
AB  - The ability to survive and proliferate at 37 degrees C is an essential virulence
      attribute of pathogenic microorganisms. A partial-genome microarray was used to
      profile gene expression in the human-pathogenic fungus Cryptococcus neoformans
      during growth at 37 degrees C. Genes with orthologs involved in stress responses
      were induced during growth at 37 degrees C, suggesting that a conserved
      transcriptional program is used by C. neoformans to alter gene expression during
      stressful conditions. A gene encoding the transcription factor homolog Mga2 was
      induced at 37 degrees C and found to be important for high-temperature growth.
      Genes encoding fatty acid biosynthetic enzymes were identified as potential
      targets of Mga2, suggesting that membrane remodeling is an important component of
      adaptation to high growth temperatures. mga2Delta mutants were extremely
      sensitive to the ergosterol synthesis inhibitor fluconazole, indicating a
      coordination of the synthesis of membrane component precursors. Unexpectedly,
      genes involved in amino acid and pyrimidine biosynthesis were repressed at 37
      degrees C, but components of these pathways were found to be required for high
      temperature growth. Our findings demonstrate the utility of even partial-genome
      microarrays for delineating regulatory cascades that contribute to microbial
      pathogenesis.

PMID- 15470255
TI  - PP2A phosphatase activity is required for stress and Tor kinase regulation of
      yeast stress response factor Msn2p.
AB  - In response to stress and nutrient starvation, the Saccharomyces cerevisiae
      transcription factor Msn2p accumulates in the nucleus and activates expression of
      a broad array of genes. Here, we analyze the role of the Tor (target of
      rapamycin) signaling pathway in mediating these responses. Inactivation of the
      Tor pathway component Tap42p using tap42(Ts) alleles causes a sustained nuclear
      localization similar to that after the addition of the Tor kinase inhibitor
      rapamycin. Effects of Tap42p inactivation and rapamycin addition could be
      suppressed by deletion of TIP41, which encodes a Tap42p-interacting protein.
      These results support the notion that rapamycin affects Msn2p by inactivating
      Tap42p function. Tap42p interacts with the catalytic subunit of PP2A (protein
      phosphatase 2A) and PP2A-like phosphatases. Deletion of either the catalytic or
      regulatory subunit that forms the PP2A phosphatase complex prevents nuclear
      accumulation of Msn2p in the tap42(Ts) strain and in wild-type strains treated
      with rapamycin. These results suggest that Tap42p is an inhibitor of PP2A
      phosphatase, which in turn inhibits nuclear export of Msn2p. Interestingly, PP2A
      function is also required for nuclear accumulation of Msn2p in response to
      stresses, such as heat and osmotic shock, as well as nitrogen (but not glucose)
      starvation. Thus, PP2A and the Tor kinase pathway transduce stress and nitrogen
      starvation signals to Msn2p. Finally, Msn2p localization is unaffected by
      conditional loss of 14-3-3 protein function, ruling out the possibility that 14-3
      3 proteins act as a scaffold to sequester Msn2p in the cytoplasm.

PMID- 15470256
TI  - Functional characterization of myosin I tail regions in Candida albicans.
AB  - The molecular motor myosin I is required for hyphal growth in the pathogenic
      yeast Candida albicans. Specific myosin I functions were investigated by a
      deletion analysis of five neck and tail regions. Hyphal formation requires both
      the TH1 region and the IQ motifs. The TH2 region is important for optimal hyphal
      growth. All of the regions, except for the SH3 and acidic (A) regions that were
      examined individually, were required for the localization of myosin I at the
      hyphal tip. Similarly, all of the domains were required for the association of
      myosin I with pelletable actin-bound complexes. Moreover, the hyphal tip
      localization of cortical actin patches, identified by both rhodamine-phalloidin
      staining and Arp3-green fluorescent protein signals, was dependent on myosin I.
      Double deletion of the A and SH3 domains depolarized the distribution of the
      cortical actin patches without affecting the ability of the mutant to form
      hyphae, suggesting that myosin I has distinct functions in these processes. Among
      the six myosin I tail domain mutants, the ability to form hyphae was strictly
      correlated with endocytosis. We propose that the uptake of cell wall remodeling
      enzymes and excess plasma membrane is critical for hyphal formation.

PMID- 15470257
TI  - FKBP12 controls aspartate pathway flux in Saccharomyces cerevisiae to prevent
      toxic intermediate accumulation.
AB  - FKBP12 is a conserved member of the prolyl-isomerase enzyme family and serves as
      the intracellular receptor for FK506 that mediates immunosuppression in mammals
      and antimicrobial actions in fungi. To investigate the cellular functions of
      FKBP12 in Saccharomyces cerevisiae, we employed a high-throughput assay to
      identify mutations that are synthetically lethal with a mutation in the FPR1
      gene, which encodes FKBP12. This screen identified a mutation in the HOM6 gene,
      which encodes homoserine dehydrogenase, the enzyme catalyzing the last step in
      conversion of aspartic acid into homoserine, the common precursor in threonine
      and methionine synthesis. Lethality of fpr1 hom6 double mutants was suppressed by
      null mutations in HOM3 or HOM2, encoding aspartokinase and aspartate beta
      semialdehyde dehydrogenase, respectively, supporting the hypothesis that fpr1
      hom6 double mutants are inviable because of toxic accumulation of aspartate beta
      semialdehyde, the substrate of homoserine dehydrogenase. Our findings also
      indicate that mutation or inhibition of FKBP12 dysregulates the homoserine
      synthetic pathway by perturbing aspartokinase feedback inhibition by threonine.
      Because this pathway is conserved in fungi but not in mammals, our findings
      suggest a facile route to synergistic antifungal drug development via concomitant
      inhibition of FKBP12 and Hom6.

PMID- 15470258
TI  - A temperature-sensitive dcw1 mutant of Saccharomyces cerevisiae is cell cycle
      arrested with small buds which have aberrant cell walls.
AB  - Dcw1p and Dfg5p in Saccharomyces cerevisiae are homologous proteins that were
      previously shown to be involved in cell wall biogenesis and to be essential for
      growth. Dcw1p was found to be a glycosylphosphatidylinositol-anchored membrane
      protein. To investigate the roles of these proteins in cell wall biogenesis and
      cell growth, we constructed mutant alleles of DCW1 by random mutagenesis,
      introduced them into a Deltadcw1 Deltadfg5 background, and isolated a temperature
      sensitive mutant, DC61 (dcw1-3 Deltadfg5). When DC61 cells were incubated at 37
      degrees C, most cells had small buds, with areas less than 20% of those of the
      mother cells. This result indicates that DC61 cells arrest growth with small buds
      at 37 degrees C. At 37 degrees C, fewer DC61 cells had 1N DNA content and most of
      them still had a single nucleus located apart from the bud neck. In addition, in
      DC61 cells incubated at 37 degrees C, bipolar spindles were not formed. These
      results indicate that DC61 cells, when incubated at 37 degrees C, are cell cycle
      arrested after DNA replication and prior to the separation of spindle pole
      bodies. The small buds of DC61 accumulated chitin in the bud cortex, and some of
      them were lysed, which indicates that they had aberrant cell walls. A temperature
      sensitive dfg5 mutant, DF66 (Deltadcw1 dfg5-29), showed similar phenotypes. DCW1
      and DFG5 mRNA levels peaked in the G1 and S phases, respectively. These results
      indicate that Dcw1p and Dfg5p are involved in bud formation through their
      involvement in biogenesis of the bud cell wall.

PMID- 15470259
TI  - Regulation of flagellar assembly by glycogen synthase kinase 3 in Chlamydomonas
      reinhardtii.
AB  - Chlamydomonas reinhardtii controls flagellar assembly such that flagella are of
      an equal and predetermined length. Previous studies demonstrated that lithium, an
      inhibitor of glycogen synthase kinase 3 (GSK3), induced flagellar elongation,
      suggesting that a lithium-sensitive signal transduction pathway regulated
      flagellar length (S. Nakamura, H. Takino, and M. K. Kojima, Cell Struct. Funct.
      12:369-374, 1987). Here, we demonstrate that lithium treatment depletes the pool
      of flagellar proteins from the cell body and that the heterotrimeric kinesin
      Fla10p accumulates in flagella. We identify GSK3 in Chlamydomonas and demonstrate
      that its kinase activity is inhibited by lithium in vitro. The tyrosine
      phosphorylated, active form of GSK3 was enriched in flagella and GSK3 associated
      with the axoneme in a phosphorylation-dependent manner. The level of active GSK3
      correlated with flagellar length; early during flagellar regeneration, active
      GSK3 increased over basal levels. This increase in active GSK3 was rapidly lost
      within 30 min of regeneration as the level of active GSK3 decreased relative to
      the predeflagellation level. Taken together, these results suggest a possible
      role for GSK3 in regulating the assembly and length of flagella.

PMID- 15470260
TI  - The Toxoplasma gondii rhoptry protein ROP4 is secreted into the parasitophorous
      vacuole and becomes phosphorylated in infected cells.
AB  - Many intracellular pathogens are separated from the cytosol of their host cells
      by a vacuole membrane. This membrane serves as a critical interface between the
      pathogen and the host cell, across which nutrients are imported, wastes are
      excreted, and communication between the two cells takes place. Very little is
      known about the vacuole membrane proteins mediating these processes in any host
      pathogen interaction. During a screen for monoclonal antibodies against novel
      surface or secreted proteins of Toxoplasma gondii, we identified ROP4, a
      previously uncharacterized member of the ROP2 family of proteins. We report here
      on the sequence, posttranslational processing, and subcellular localization of
      ROP4, a type I transmembrane protein. Mature, processed ROP4 is localized to the
      rhoptries, secretory organelles at the apical end of the parasite, and is
      secreted from the parasite during host cell invasion. Released ROP4 associates
      with the vacuole membrane and becomes phosphorylated in the infected cell.
      Similar results are seen with ROP2. Further analysis of ROP4 showed it to be
      phosphorylated on multiple sites, a subset of which result from the action of
      either host cell protein kinase(s) or parasite kinase(s) activated by host cell
      factors. The localization and posttranslational modification of ROP4 and other
      members of the ROP2 family of proteins within the infected cell make them well
      situated to play important roles in vacuole membrane function.

PMID- 15470261
TI  - Insights into the survival of Chlamydomonas reinhardtii during sulfur starvation
      based on microarray analysis of gene expression.
AB  - Responses of photosynthetic organisms to sulfur starvation include (i) increasing
      the capacity of the cell for transporting and/or assimilating exogenous sulfate,
      (ii) restructuring cellular features to conserve sulfur resources, and (iii)
      modulating metabolic processes and rates of cell growth and division. We used
      microarray analyses to obtain a genome-level view of changes in mRNA abundances
      in the green alga Chlamydomonas reinhardtii during sulfur starvation. The work
      confirms and extends upon previous findings showing that sulfur deprivation
      elicits changes in levels of transcripts for proteins that help scavenge sulfate
      and economize on the use of sulfur resources. Changes in levels of transcripts
      encoding members of the light-harvesting polypeptide family, such as LhcSR2,
      suggest restructuring of the photosynthetic apparatus during sulfur deprivation.
      There are also significant changes in levels of transcripts encoding enzymes
      involved in metabolic processes (e.g., carbon metabolism), intracellular
      proteolysis, and the amelioration of oxidative damage; a marked and sustained
      increase in mRNAs for a putative vanadium chloroperoxidase and a peroxiredoxin
      may help prolong survival of C. reinhardtii during sulfur deprivation.
      Furthermore, many of the sulfur stress-regulated transcripts (encoding
      polypeptides associated with sulfate uptake and assimilation, oxidative stress,
      and photosynthetic function) are not properly regulated in the sac1 mutant of C.
      reinhardtii, a strain that dies much more rapidly than parental cells during
      sulfur deprivation. Interestingly, sulfur stress elicits dramatic changes in
      levels of transcripts encoding putative chloroplast-localized chaperones in the
      sac1 mutant but not in the parental strain. These results suggest various
      strategies used by photosynthetic organisms during acclimation to nutrient
      limited growth.

PMID- 15470263
TI  - Rapid production of gene replacement constructs and generation of a green
      fluorescent protein-tagged centromeric marker in Aspergillus nidulans.
AB  - A method to rapidly generate gene replacement constructs by fusion PCR is
      described for Aspergillus nidulans. The utility of the approach is demonstrated
      by green fluorescent protein (GFP) tagging of A. nidulans ndc80 to visualize
      centromeres through the cell cycle. The methodology makes possible large-scale
      GFP tagging, promoter swapping, and deletion analysis of A. nidulans.

PMID- 15470262
TI  - CbfA, the C-module DNA-binding factor, plays an essential role in the initiation
      of Dictyostelium discoideum development.
AB  - We recently isolated from Dictyostelium discoideum cells a DNA-binding protein,
      CbfA, that interacts in vitro with a regulatory element in retrotransposon TRE5
      A. We have generated a mutant strain that expresses CbfA at <5% of the wild-type
      level to characterize the consequences for D. discoideum cell physiology. We
      found that the multicellular development program leading to fruiting body
      formation is highly compromised in the mutant. The cells cannot aggregate and
      stay as a monolayer almost indefinitely. The cells respond properly to
      prestarvation conditions by expressing discoidin in a cell density-dependent
      manner. A genomewide microarray-assisted expression analysis combined with
      Northern blot analyses revealed a failure of CbfA-depleted cells to induce the
      gene encoding aggregation-specific adenylyl cyclase ACA and other genes required
      for cyclic AMP (cAMP) signal relay, which is necessary for aggregation and
      subsequent multicellular development. However, the cbfA mutant aggregated
      efficiently when mixed with as few as 5% wild-type cells. Moreover, pulsing cbfA
      mutant cells developing in suspension with nanomolar levels of cAMP resulted in
      induction of acaA and other early developmental genes. Although the response was
      less efficient and slower than in wild-type cells, it showed that cells depleted
      of CbfA are able to initiate development if given exogenous cAMP signals. Ectopic
      expression of the gene encoding the catalytic subunit of protein kinase A
      restored multicellular development of the mutant. We conclude that sensing of
      cell density and starvation are independent of CbfA, whereas CbfA is essential
      for the pattern of gene expression which establishes the genetic network leading
      to aggregation and multicellular development of D. discoideum.

PMID- 15470264
TI  - Smokeless tobacco and oral cancer: a review of the risks and determinants.
AB  - Smokeless tobacco has been associated with oral cancer for many decades. The
      purpose of this article is to review research relevant to this association,
      including epidemiologic studies, studies of putative carcinogens such as tobacco
      specific nitrosamines (TSNAs) and other contaminants, and possible cancer
      inhibitors. Epidemiologic studies addressing this issue primarily consist of case
      control studies. They show that the use of chewing tobacco and moist snuff is
      associated with very low risks for cancers of the oral cavity and related
      structures (relative risks [RR] from 0.6 to 1.7). The use of dry snuff is
      associated with higher RRs, ranging from 4 to 13, while the RRs from smokeless
      tobacco, unspecified as to type, are intermediate (RR = 1.5 to 2.8). With regard
      to TSNAs, historical levels in American moist snuff products were higher than
      those in their Swedish counterparts, but levels in contemporary products are
      uniformly low. TSNA levels in chewing tobacco have always been low, but levels in
      dry snuff have been higher, including some very high levels in current products.
      In general, smokeless tobacco users are not exposed to significant levels of
      cadmium, lead, benzo(a)pyrene, polonium-210, and formaldehyde, when compared with
      concentrations of these compounds in foods. Finally, low oral cancer risk from
      smokeless tobacco use may be influenced by the presence of cancer inhibitors,
      mainly anti-oxidants, in smokeless tobacco products.

PMID- 15470266
TI  - Zinc finger transcription factors in skeletal development.
AB  - Cellular and molecular processes that regulate the development of skeletal
      tissues resemble those required for regeneration. Given the prevalence of
      degenerative skeletal disorders in an increasingly aging population, the
      molecular mechanisms of skeletal development must be understood in detail if
      novel strategies are to be developed in regenerative medicine. Research in this
      area over the past decade has revealed that cell differentiation is largely
      controlled at the level of gene transcription, which in turn is regulated by
      transcription factors. Transcription factors usually recognize and bind to
      specific DNA sequences in the promoter of target genes via characteristic DNA
      binding domains. Although the gene family containing C2H2 zinc fingers as DNA
      binding motifs is the largest family of transciptional regulators, with several
      hundred individual members in mammals, only a small but increasing number of zinc
      finger genes have been implicated in bone, cartilage, or tooth development. These
      zinc finger proteins (ZFPs) contain multiple structural motifs that require zinc
      to maintain their structural integrity and function. Interestingly, zinc
      deficiency is known to result in skeletal growth retardation and has been
      identified as a risk factor in the pathogenesis of osteoporosis. This review
      attempts to summarize our current state of knowledge regarding the role of ZFPs
      in the molecular regulation of skeletogenesis.

PMID- 15470267
TI  - Signal transducers and activators of transcription: insights into the molecular
      basis of oral cancer.
AB  - Recent efforts on developing more direct and effective targets for cancer therapy
      have revolved around a family of transcription factors known as STATs (signal
      transducers and activators of transcription). STAT proteins are latent
      cytoplasmic transcription factors that become activated in response to
      extracellular signaling proteins. STAT proteins have been convincingly reported
      to possess oncogenic properties in a plethora of human cancers, including oral
      and oropharyngeal cancer. Signal transduction pathways mediated by these
      oncogenic transcription factors and their regulation in oral cancer are the focus
      of this review.

PMID- 15470265
TI  - The wrickkened pathways of FGF23, MEPE and PHEX.
AB  - The last 350 years since the publication of the first medical monograph on
      rickets (old English term wrickken) (Glisson et al., 1651) have seen spectacular
      advances in our understanding of mineral-homeostasis. Seminal and exciting
      discoveries have revealed the roles of PTH, vitamin D, and calcitonin in
      regulating calcium and phosphate, and maintaining healthy teeth and skeleton.
      However, it is clear that the PTH/Vitamin D axis does not account for the entire
      picture, and a new bone-renal metabolic milieu has emerged, implicating a novel
      set of matrix proteins, hormones, and Zn-metallopeptidases. The primary defects
      in X-linked hypophosphatemic rickets (HYP) and autosomal-dominant
      hypophosphatemic rickets (ADHR) are now identified as inactivating mutations in a
      Zn-metalloendopeptidase (PHEX) and activating mutations in fibroblast-growth
      factor-23 (FGF23), respectively. In oncogenic hypophosphatemic osteomalacia
      (OHO), several tumor-expressed proteins (MEPE, FGF23, and FRP-4) have emerged as
      candidate mediators of the bone-renal pathophysiology. This has stimulated the
      proposal of a global model that takes into account the remarkable similarities
      between the inherited diseases (HYP and ADHR) and the tumor-acquired disease OHO.
      In HYP, loss of PHEX function is proposed to result in an increase in uncleaved
      full-length FGF23 and/or inappropriate processing of MEPE. In ADHR, a mutation in
      FGF23 results in resistance to proteolysis by PHEX or other proteases and an
      increase in half-life of full-length phosphaturic FGF23. In OHO, over-expression
      of FGF23 and/or MEPE is proposed to result in abnormal renal-phosphate handling
      and mineralization. Although this model is attractive, many questions remain
      unanswered, suggesting a more complex picture. The following review will present
      a global hypothesis that attempts to explain the experimental and clinical
      observations in HYP, ADHR, and OHO, plus diverse mouse models that include the
      MEPE null mutant, HYP-PHEX transgenic mouse, and MEPE-PHEX double-null-mutant.

PMID- 15470268
TI  - Virulence factors of Enterococcus faecalis: relationship to endodontic disease.
AB  - Enterococcus faecalis is a micro-organism that can survive extreme challenges.
      Its pathogenicity ranges from life-threatening diseases in compromised
      individuals to less severe conditions, such as infection of obturated root canals
      with chronic apical periodontitis. In the latter situation, the infecting
      organisms are partly shielded from the defense mechanisms of the body. In this
      article, we review the virulence factors of E. faecalis that may be related to
      endodontic infection and the periradicular inflammatory response. The most-cited
      virulence factors are aggregation substance, surface adhesins, sex pheromones,
      lipoteichoic acid, extracellular superoxide production, the lytic enzymes
      gelatinase and hyaluronidase, and the toxin cytolysin. Each of them may be
      associated with various stages of an endodontic infection as well as with
      periapical inflammation. While some products of the bacterium may be directly
      linked to damage of the periradicular tissues, a large part of the tissue damage
      is probably mediated by the host response to the bacterium and its products.

PMID- 15470269
TI  - Oxidative stress in NRTI-induced toxicity: evidence from clinical experience and
      experiments in vitro and in vivo.
AB  - This article reviews the relationship of oxidative stress with nucleoside reverse
      transcriptase inhibitor (NRTI)-induced toxicity and suggests how oxi-dative
      stress may participate in NRTI-mediated toxicity. NRTIs are pro-drugs that
      require intracellular phosphorylation to their 5' triphosphates by cellular
      kinases to inhibit viral and mitochondrial DNA (mtDNA) replication. NRTIs in
      highly active antiretroviral therapy have decreased morbidity and mortality, but
      side effects can be limiting after prolonged use. These side effects may be
      linked through mitochondrial dysfunction arising from altered mtDNA replication
      and oxidative stress via destruction of elements of mtDNA replication, decreased
      oxidative phosphorylation, and cellular function. Although oxidative stress is
      associated with NRTI therapy, there is still debate about whether it plays a
      direct role in NRTI-induced toxicity. The impact of oxidative stress on
      cardiovascular disease is likely to increase because patients with HIV infection
      are living longer as a result of effective antiretroviral therapy.

PMID- 15470270
TI  - Direct, DNA pol-gamma-independent effects of nucleoside reverse transcriptase
      inhibitors on mitochondrial bioenergetics.
AB  - Nucleoside reverse transcriptase inhibitor (NRTI)-induced cardiomyopathy has been
      suggested to reflect mitochondrial targets of drug toxicity. The prevailing
      hypothesis is that, through structural mimicry, the NRTIs are mistaken as
      substrates for DNA polymerase and incorporated into replicating DNA, where they
      cause truncation of the elongating strand. Although there exist five forms of
      nuclear DNA polymerase, mitochondria possess solely DNA polymerase-gamma (pol
      gamma), which is a preferred target for most NRTIs. Consequently, mitochondria
      are particularly susceptible to inhibition of DNA replication by the NRTIs, which
      is consistent with the phenotype of mitochondrial depletion and metabolic failure
      in affected patients. However, the DNA pol-gamma hypothesis by itself fails to
      explain the entire array of metabolic deficiencies associated with NRTI-induced
      disorders. In this article, we review the published literature regarding the
      direct effects of NRTIs on various mitochondrial targets and suggest the
      possibility that the initiating event in NRTI-induced cardiomyopathy is a direct
      mitochondrial toxicity rather than inhibition of mitochondrial DNA pol-gamma. The
      goal of this review is to encourage a discussion of the cause of NRTI-induced
      mitochondrial cardiomyopathy to include a fresh consideration of all possible
      targets and integrating pathways that are involved in establishing mitochondrial
      bioenergetic fidelity and metabolic capacity in the affected myocardium.

PMID- 15470271
TI  - HIV/AIDS-related cardiovascular disease.
AB  - Recent advances in antiretroviral therapies have enhanced survival of HIV/AIDS
      patients, but cardiovascular complications have emerged as important issues in
      this growing patient population. Although the antiviral drug therapies apparently
      yield cardiac and/or vascular toxicities themselves, several other factors
      associated with HIV pathogenesis have also been implicated. This brief review
      provides an overview of the significance and complexities of HIV/ AIDS-related
      cardiovascular complications and addresses some important mechanistic aspects
      that may contribute to this important clinical problem.

PMID- 15470272
TI  - Cardiovascular toxicity with highly active antiretroviral therapy: review of
      clinical studies.
AB  - Highly active antiretroviral therapy (HAART) has dramatically improved the life
      expectancy of patients with human immunodeficiency virus (HIV). Specific
      toxicities cited for HAART include elevations in serum levels of total
      cholesterol and triglycerides, reduction in high-density lipoprotein cholesterol,
      alterations in the distribution of body fat, increases in insulin resistance, and
      diabetes, which are major risk factors for cardiovascular disease (CVD). The
      majority of the studies examining the incidence of CV events demonstrated an
      increase in CV event rate with HAART in the HIV-infected population. Overall, the
      CVD risk appears to be greater in the HIV-infected population than in the general
      population, and the increased CV risk is associated with HAART, particularly with
      protease inhibitor use. Despite the relative risk (RR) for CVD being
      significantly high (the hazard ratio for myocardial infarction ranging between
      1.3 and 7.1), the absolute risk for CVD remains low, with the CV event rates
      ranging between one and seven events per 1000 person-years. Although there is
      general consensus that the benefits of HAART far outweigh toxicity-related risks
      of the treatment with HAART, prolonged survival among HIV-infected patients will
      likely support the use of different antiretroviral regimens with potentially less
      CV toxicity in the future.

PMID- 15470273
TI  - Clinical aspects of endothelial dysfunction associated with human
      immunodeficiency virus infection and antiretroviral agents.
AB  - Endothelial dysfunction is a critical initial step of atherogenesis that
      subsequently contributes to the progression and clinical manifestations of
      atherosclerosis. The use of human immunodeficiency virus type 1 (HIV-1) protease
      inhibitor (PI) agents has been associated with increased cardiovascular events
      and worsening of multiple coronary heart disease risk factors including dys
      lipidemia, insulin resistance, and endothelial dysfunction. Endothelial
      dysfunction may be caused by HIV infection itself as well as treatment-related
      effects of the antiretroviral agents used to treat HIV. The available evidence
      suggests that PIs may induce endothelial dysfunction via their effects on both
      lipid and glucose metabolism. Studies in healthy subjects confirm a role for
      reduced endothelial nitric oxide production in the endothelial dysfunction
      associated with the PI indinavir. Further work is needed to determine the
      relative tendencies of other antiretroviral agents to induce endothelial
      dysfunction, the physiologic mechanisms involved, and the contribution of the
      metabolic and body shape changes associated with HIV treatment-related
      lipodystrophy, and to establish effective interventions for endothelial
      dysfunction in HIV-infected patients.

PMID- 15470274
TI  - Cardiovascular effects of HAART in infants and children of HIV-infected mothers.
AB  - Over the past decade, the course of human immunodeficiency virus (HIV) infection
      has been markedly altered by highly active antiretroviral therapy (HAART). As
      advances in early diagnosis and aggressive therapy, as well as better supportive
      care, become available to more HIV-infected patients, survival is being prolonged
      and more patients are experiencing cardiac abnormalities. Cardiovascular
      manifestations of pediatric HIV infection have especially proven to be an ongoing
      challenge to practicing physicians, who face cardiac abnormalities ranging from
      asymptomatic cardiomyopathy to severe heart failure. Antiretroviral therapy has
      substantially decreased vertical transmission of HIV; however, studies of adults
      receiving HAART have found increased peripheral and coronary artery disease.
      Children exposed to this therapy in utero are thus at an increased risk for
      toxicity and cardiac abnormalities, regardless of their HIV status. Preliminary
      studies have reported complications including lactic acidosis and mitochondrial
      toxicity, as well as cardiomyopathy. Further studies are needed to explore the
      long-term effects and possible toxicities of prophylactic antiretroviral therapy
      on infants born to HIV-infected mothers.

PMID- 15470275
TI  - Cardiovascular effects of antiretroviral therapy and noninvasive assessments of
      cardiovascular disease in HIV infection.
AB  - The heart is frequently affected in patients with the acquired immune deficiency
      syndrome (AIDS). Although the introduction of potent antiretroviral therapy (ART)
      has produced a sharp decline in mortality and morbidity in HIV-infected patients,
      the use of ART is associated with the development of peripheral insulin
      resistance, dyslipidemia, and lipodystrophy. These abnormalities are also
      associated with coronary artery disease, and numerous reports of myo-cardial
      infarction in young HIV-infected patients have raised concerns of pre-mature
      coronary disease in this population. A comprehensive review of the epidemiology
      of coronary artery disease is given. In recent years, several non-invasive
      methods to detect early development of atherosclerosis have been evaluated. Two
      noninvasive techniques using ultrasound have emerged as valid methods to detect
      early development of atherosclerosis: intima-media thickness and endothelial
      dysfunction assessed by the measurement of flow-mediated brachial artery
      dilatation. Multicenter, randomized trials using either technique may provide
      more information about whether HIV infection alone, long-term HAART use, or both
      may increase the risks of or accelerate coronary disease in HIV-infected
      patients.

PMID- 15470276
TI  - HAART drugs induce oxidative stress in human endothelial cells and increase
      endothelial recruitment of mononuclear cells: exacerbation by inflammatory
      cytokines and amelioration by antioxidants.
AB  - Highly active antiretroviral therapy (HAART) has significantly improved the
      prognosis of HIV-1-infected patients but is associated with significant side
      effects such as diabetes, atherosclerosis, and cardiovascular complications.
      Oxidative stress can disrupt endothelial homeostasis by dysregulating the balance
      between pro- and antiatherogenic factors. We hypothesized that chronic exposure
      to HAART results in endothelial oxidative stress and activation of mononuclear
      cell recruitment, an early event in atherosclerosis. We studied the effects of
      HAART drug combinations, consisting of zidovudine, a nucleoside reverse
      transcriptase inhibitor; efavirenz, a nonnucleoside reverse transcriptase
      inhibitor; and either of the two protease inhibitors (PIs), indinavir or
      nelfinavir, on human aortic endothelial cells (HAECs) by monitoring the following
      parameters: (1) generation of reactive oxygen species (ROS), (2) mono-nuclear
      cell (Jurkat or U-937) adhesion, and (3) expression of cell adhesion molecules
      (CAMs). HAART exposure increased ROS formation in HAECs. Exposure to PIs alone
      and in HAART combinations increased mononuclear cell adhesion to HAECs in a
      concentration-dependent manner. Mononuclear cell adhesion to HAART-exposed HAECs
      was significantly enhanced following acute (24-h) exposure to the inflammatory
      cytokines, tumor necrosis factor (TNF)-alpha or interleukin (IL)-1beta and was
      suppressed by the antioxidants N-ace-tylcysteine and glutathione. Exposure to
      HAART increased intercellular adhesion molecule-1 (ICAM-1) gene expression and
      concomitant exposure to TNF-alpha further increased ICAM-1, vascular cell
      adhesion molecule-1 (VCAM-1), and endothelial-leukocyte adhesion molecule cell
      surface protein levels. These studies indicate that chronic HAART exposure
      increases oxidative stress in endothelial cells and induces mononuclear cell
      recruitment, which may eventually precipitate the cardiovascular diseases
      observed in HIV-1+ individuals on antiretroviral therapy.

PMID- 15470278
TI  - Trends in medical education: challenges and directions for need-based reforms of
      medical training in South-East Asia.
AB  - Most medical schools, especially in South-East Asia, currently are experiencing
      difficulties in providing the right quality and quantity of educational
      experiences as the curricula have failed to respond to the needs of the community
      and country. The pedagogic shift from traditional approach to a need-based
      approach requires a fundamental change of the roles and commitments of educators,
      planners and policymakers. Teachers of health professional education in the
      region are to be well-informed of the trends and innovations and utilize these to
      increase relevance and quality of education to produce competent human resources
      for the region. The purpose of this paper is twofold: (i) to discuss innovative
      strategies and emerging trends, which have been successfully adopted by educators
      around the world for the reorientation of medical education to overcome existing
      traditions of educational planning, review and development and (ii) to highlight
      their implications and importance to initiate need-based reforms of medical
      training in South-East Asia.

PMID- 15470277
TI  - HIV, metabolic syndrome X, inflammation, oxidative stress, and coronary heart
      disease risk : role of protease inhibitor exposure.
AB  - Differences on measures of metabolic syndrome X and coronary heart disease (CHD)
      risk, as well as potential pathophysiological mediators, inflammation, and
      oxidative stress, were examined as a function of HIV serostatus and highly active
      antiretroviral therapy (HAART) regimen with and without protease inhibitors
      (PIs). Data from 164 men and women, aged 18 to 55 yr, were used to compare 82
      HIV+ subjects who were free of hepatitis C virus and were on a stable HAART
      regimen for >/=6 mo, with 82 seronegative subjects matched on age, sex, body mass
      index, and ethnicity. For the HIV+ subjects, after controlling for diabetes
      status and HIV disease progression, PI exposure was associated with greater
      oxidative stress, triglyceridemia, and lipidemia than it was for non-PI-exposed
      HIV+ subjects, and the risk of a future myocardial infarction was up to 56%
      greater in PI-exposed than in non-PI-exposed subjects and 129% greater than in
      controls. Although it is likely that the greatest proportion of CHD risk in the
      HIV+ subjects may be accounted for by pathological conditions linked to HIV
      infection in interaction with mediating processes such as inflammation, central
      obesity, and dyslipidemia, which was greater than in controls, it appears that PI
      medications may exacerbate oxidative stress and hypertriglyceridemia to enhance
      this risk.

PMID- 15470279
TI  - Combination of thrombophilia markers in acute myocardial infarction of the young.
AB  - BACKGROUND: The pathogenesis of arterial thrombotic disease involves multiple
      genetic and environmental factors related to atherosclerosis and thrombosis. But,
      there have been very few studies in India which have investigated some of the
      thrombophilia markers. AIM: To look for combined thrombophilia in MI patients.
      SETTINGS AND DESIGN: One hundred twenty patients of myocardial infarction (age
      below 40 yrs.) were recruited 8-10 weeks after stabilization. Hundred age and sex
      matched healthy controls were also recruited in the present study. METHODS AND
      MATERIAL: Following thrombophilia markers were screened in these patients--plasma
      fibrinogen, protein C, protein S, antithrombin III, factor V Leiden, PT G20210A
      polymorphism, MTHFR C677T, homocysteine, fibrinogen b448 Arg/Lys polymorphism and
      CBS T833C mutation. STATISTICAL ANALYSIS: Statistical analysis was done using
      Statistical Package for Social Sciences (SPSS) version 10.0, SPSS Inc., Chicago,
      USA. RESULTS AND CONCLUSION: Elevated fibrinogen levels, homocysteine (p< 0.001
      and homocysteine with odds ratio 6.26) and factor V Leiden (p=0.038) were
      independently associated with MI in our patients. A total of 37 patients (42.5%)
      had the presence of more than one thrombophilia markers in combination. Out of
      these, 10 had the presence of three markers in combination and 1 had five
      thrombophilia markers in combination. Only 2 controls had prothrombotic markers
      in combination. Combined prothrombotic risk factors were significant in cases in
      comparison to controls (p< 0.001). Further larger studies on a nationwide basis
      recruiting a large number of young MI patients should be done to substantiate
      these findings.

PMID- 15470280
TI  - Iron deficiency amongst nursing students.
AB  - CONTEXT: Iron deficiency anemia (IDA) is widely prevalent in India. IDA is
      preceded by a stage of latent iron deficiency (ID) where serum ferritin is
      reduced but hemoglobin is normal. AIMS: Present study was undertaken (1) to find
      prevalence of IDA and ID amongst nursing students; (2) to observe effect of
      hematinic therapy on Hb and red cell indices. SETTINGS AND DESIGN: Nursing
      students were taken up for study after they gave a written consent. METHODS AND
      MATERIAL: Subjects were given a written questionnaire to elicit anemia related
      symptoms. Blood counts were done on electronic counter and serum ferritin was
      assayed by Elisa. Hematinic capsule was given once at bedtime for a period of
      three months, after which, participants again answered the same questionnaire and
      blood count was done. STATISTICAL ANALYSIS USED: Students' t test was used to
      compare the results. RESULTS: There was no significant difference in Hb, MCV and
      MCH of normal and ID group. Differences in Hb, MCV and MCH between normal and IDA
      groups and between IDA and ID groups were highly significant (p < 0.001). Symptom
      score did not show significant difference in three groups. Ferritin levels of ID
      and IDA groups were significantly lower than that of normal group (p < 0.001)
      whereas there was no significant difference in ferritin levels of ID and IDA
      groups. IDA group showed highly significant improvement in Hb, MCV and MCH as a
      result of treatment. ID and normal groups did not show increase in Hb level after
      treatment but increase in MCV and MCH in both groups were highly significant.
      CONCLUSIONS: IDA and ID were found in 20.3% and 27.5% subjects respectively.
      Significant rise in MCV and MCH in normal group indicated that even this
      apparently normal group had iron deficient erythropoiesis.

PMID- 15470281
TI  - Microbial and cytopathological study of intrauterine contraceptive device users.
AB  - CONTEXT: Intrauterine contraceptive device (IUCD) is a commonly used birth
      spacing method which is fitted into maternal system. Clinical, microbial and
      cytopathological monitoring of women using these devices are important for
      ascertaining their side effects, risk of genital tract infection and carcinogenic
      potential. AIMS: To study clinical, microbial and cytopathological changes in
      IUCD users in a tertiary care hospital. DESIGN: Prospective analytic. SETTING:
      Tertiary hospital. MATERIAL AND METHODS: women visiting Family Planning clinic
      for follow up (IUCD users, n=100) or for IUCD insertion (controls, n=50) were
      enrolled in the study. Each subject underwent detailed history, general physical,
      systemic, and per local examination. Vaginal discharge was subjected to pH
      testing, KOH and wet mount examination, gram staining, and for culture and
      sensitivity. Bacterial vaginosis was defined using Nugent criteria. Cervical
      smears were examined and reported as per Bethesda system. STATISTICAL ANALYSIS:
      The information was entered into Microsoft Excel spreadsheet. The results were
      analyzed using EPI Info version-6 and Stata statistical software version 7
      packages. Two-tailed t-test, chi2 test with Yates correction and two-tailed
      Fisher Exact tests were applied. RESULTS: Most women used CuT 200 (92%). Median
      duration of use was 2 years. Chief complaints of IUCD users included backache
      (54%), vaginal discharge (46%), pain lower abdomen (34%), dyspareunia (22%),
      menorrhagia (18%) and dysmenorrhea (14%). Mean hemoglobin was lower in IUCD users
      than controls (11.2+/-1.7 versus 11.9+/-1.8 g/dL, p 0.02). Proportion of women
      with anemia was higher in IUCD users than in controls (29% versus 16%, p 0.12).
      Cervical erosion was significantly increased in study group as compared the
      controls (20% versus 0%, p=0.00) whereas only insignificant increase in vaginitis
      (6% versus 0%, p=0.17). Trichomonas vaginalis and fungal hyphae positivity and
      gram stain findings and bacterial vaginosis rate were not significantly different
      in two groups. Vaginal discharge bacterial culture revealed comparable results in
      two groups. Cytological findings were predominantly inflammatory. None of cases
      revealed Actinomycosis infection. High-grade squamous intraepithelial lesion
      (n=2) and low grade squamous intraepithelial lesion (n=1) cytological finding
      were present in IUCD users compared to none in controls. None of the cases had
      any malignant transformation. CONCLUSION: IUCD use results in lower hemoglobin
      concentration and cervical erosion. Women using IUCD requires a regular follow
      up, clinical examination, counseling and further investigation if required.

PMID- 15470282
TI  - Hemolytic anemia.

PMID- 15470283
TI  - Chronic kidney disease: it's time to recognize its presence in our patients with
      hypertension.

PMID- 15470284
TI  - Graded blood pressure reduction in hypertensive outpatients associated with use
      of a device to assist with slow breathing.
AB  - To study the effects of device-guided breathing on office systolic blood pressure
      (SBP), five centers randomized 149 untrained hypertensives (50% male, age 59+/-10
      years, baseline blood pressure 150+/-9/86+/-9 mm Hg, 77% taking drug therapy).
      One half received a device to guide slow breathing; all received a home blood
      pressure monitor and only simple, written instructions. The changes in office SBP
      (adjusted for office-to-home difference in baseline SBP and accumulated time
      spent in slow breathing, guided and measured by the device) were significantly
      (p<0.001 for trend) correlated with accumulated time spent in slow breathing.
      Greater decreases in SBP (-15.0+/-1.8 vs. -7.3+/-1.9 mm Hg) were observed for
      those who spent more (vs. less) than 180 minutes over 8 weeks in slow breathing,
      as well as those who just monitored their blood pressure at home (-9.2+/-1.6 mm
      Hg). Thus, even without training, hypertensive patients who receive a device to
      guide slow breathing significantly lowered their office SBP if the total time
      spent in slow breathing over 8 weeks exceeded a "threshold" value of 180 minutes.

PMID- 15470285
TI  - Elevation of C-reactive protein in people with prehypertension.
AB  - The objective of this study was to determine the relationship of C-reactive
      protein (CRP) and blood pressure (BP) across the range of BP categories including
      prehypertension. The Third National Health and Nutrition Examination Survey
      (NHANES III) data collected from 1988 to 1994 were analyzed. In unadjusted
      analyses, there was a step-wise increase in the probability of elevated CRP
      across a wide range of BP categories. Prehypertensive participants had a higher
      prevalence of elevated CRP than normotensive people (27.4% vs. 19.8%; p<05).
      After adjustment for age, gender, race, smoking, body mass index, exercise,
      diabetes, and medication usage, participants with systolic BP 120-139 mm Hg or
      diastolic BP 80-89 mm Hg were more likely to have elevated CRP than people with
      systolic BP <120 (odds ratio, 1.36; 95% confidence interval, 1.14-1.62; odds
      ratio, 1.20; 95% confidence interval, 1.02-1.41, respectively). CRP and BP are
      positively related across a wide range of BP categories. A substantial proportion
      of prehypertensive individuals have elevated CRP independent of multiple
      confounders.

PMID- 15470286
TI  - Antihypertensive efficacy of angiotensin receptor blockers in combination with
      hydrochlorothiazide: a review of the factorial-design studies.
AB  - Most hypertensive patients require more than one drug for adequate blood pressure
      (BP) control. The seventh report of the Joint National Committee on Prevention,
      Detection, Evaluation, and Treatment of High Blood Pressure recommends starting
      treatment with a thiazide diuretic or, when BP is >20/10 mm Hg above goal or in
      patients with diabetes, using two different antihypertensive agents. Searches of
      Medline, EMBASE, and BIOSIS databases identified four similarly designed,
      randomized, factorial studies comparing various doses of angiotensin II receptor
      blockers with hydrochlorothiazide as monotherapy and in combination. The
      methodology and results of these studies were compared. The primary efficacy end
      point in these studies was a decrease from baseline in mean diastolic BP after 8
      weeks of therapy. All currently available angiotensin I receptor
      blocker/hydrochlorothiazide combinations evaluated (irbesartan, olmesartan
      medoxomil, telmisartan, and valsartan plus hydrochlorothiazide) produced
      significant systolic BP and diastolic BP reductions. Olmesartan
      medoxomil/hydrochlorothiazide 40 mg/25 mg provided the largest mean reduction in
      absolute and placebo-corrected systolic BP/diastolic BP. For all angiotensin II
      receptor blocker/hydrochlorothiazide combinations evaluated, > or =63% of
      patients achieved a diastolic BP response (diastolic BP <90 mm Hg or > or =10-mm
      Hg reduction). In conclusion, the combination of an angiotensin II receptor
      blocker and hydrochlorothiazide produces more substantial BP responses than
      monotherapy with either component.

PMID- 15470287
TI  - Lifestyle modification: is it achievable and durable? The argument for.

PMID- 15470288
TI  - Lifestyle modification: is it achievable and durable? The argument against.

PMID- 15470289
TI  - Clinical features and management of selected hypertensive emergencies.
AB  - A hypertensive emergency, defined as an elevated blood pressure with evidence of
      acute target organ damage, can manifest in many forms, including neurological,
      cardiac, renal, and obstetric. After diagnosis, effective parenteral
      antihypertensive therapy (typically, nitroprusside starting at 0.5 microg/kg/min,
      but some physicians prefer fenoldopam or nicardipine) should be given in the
      hospital. In general, blood pressure should be reduced about 10% during the first
      hour and another 15% gradually over 2-3 more hours. The exception is aortic
      dissection, for which treatment includes a b blocker, and the target is systolic
      blood pressure <120 mm Hg after 20 minutes. Oral antihypertensive therapy can
      usually be instituted after 6-12 hours of parenteral therapy. Consideration
      should be given to secondary causes of hypertension after transfer from the
      intensive care unit. Because of advances in antihypertensive therapy and
      management, "malignant hypertension" should be malignant no longer.

PMID- 15470290
TI  - Blunted nocturnal decline in blood pressure.
AB  - Blood pressure normally declines 10%-20% from daytime to sleep. Patients with
      less than a 10% reduction in daytime blood pressure are referred to as
      nondippers. A blunted nocturnal decline in blood pressure may be due to
      diminished sodium excretory capacity, alteration in the autonomic nervous system,
      or other factors. Secondary hypertension should be considered as a possibility.
      Target organ damage appears to be more common in nondippers, however, poor
      reproducibility of nondipping status raises the question as to the appropriate
      duration of monitoring to establish a diagnosis. Nondippers tend to have a
      greater reduction in nocturnal blood pressure with nonpharmacologic and
      pharmacologic treatment.

PMID- 15470293
TI  - Update on the management of hypertension: recent clinical trials and the JNC 7.
AB  - The following issues are highlighted: Emphasis is placed on the importance of
      systolic blood pressure elevations in estimating risk and in determining
      prognosis. A review of placebo-controlled clinical trials indicates that
      cardiovascular events are statistically significantly reduced with diuretic- or b
      blocker-based treatment regimens. The question of whether blood pressure lowering
      alone or specific medications make the difference in outcome is discussed. Based
      on the results of numerous trials, it is apparent that blood pressure lowering
      itself is probably of greater importance in reducing cardiovascular events than
      the specific medication used. Meta-analyses suggest, however, that the use of an
      agent that blocks the renin-angiotensin aldosterone system is probably more
      effective in diabetics and in patients with nephropathy than a regimen based on
      calcium channel blocker therapy. The Antihypertensive and Lipid-Lowering
      treatment to Prevent Heart Attack Trial (ALLHAT) reported no overall difference
      in coronary heart disease outcome among patients treated with a diuretic-based
      compared to a calcium channel blocker- or an angiotensin-converting enzyme
      inhibitor-based treatment program. However, patients in the diuretic group
      experienced fewer episodes of heart failure than in the calcium channel blocker
      group and fewer episodes of heart failure and strokes than those in the
      angiotensin-converting enzyme inhibitor group. Results were similar in diabetics
      and nondiabetics. Possible reasons for this outcome are discussed. The Australian
      National Blood Pressure 2 study, which was unblinded, reported a marginally
      significantly better outcome only in male patients receiving an angiotensin
      converting enzyme inhibitor-based regimen compared to those receiving a diuretic
      based program. Finally, the Seventh Report of the Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)
      is reviewed. Highlights of this report include the new designation of
      prehypertension, i.e., blood pressures of 120-139 mm Hg/80-89 mm Hg. The JNC 7
      suggested that diuretics should be the first-step drug of choice in most
      patients, but listed numerous specific reasons why other agents should be used in
      special situations. The report stressed that the majority of patients will
      require two or more medications to achieve goal blood pressure.

PMID- 15470294
TI  - From hypertension to heart failure.
AB  - The prevalence of heart failure is increasing in modern societies. Hypertension
      is a major contributor to the development of heart failure, whether through the
      development of left ventricular hypertrophy and diastolic dysfunction or by
      promoting atherosclerosis and myocardial infarction, which eventually leads to
      systolic dysfunction and left ventricular dysfunction. Effective therapy for
      hypertension can prevent more than 50% of heart failure events. Most studies done
      in the last three decades have used b blockers with diuretics as the modality of
      therapy. These agents have been shown to effectively prevent the development of
      heart failure. More recent comparative studies have shown that use of angiotensin
      converting enzyme inhibitors and angiotensin receptor blockers are also effective
      in preventing heart failure. Calcium channel blockers, however, seem to be less
      effective in preventing development of heart failure in patients with
      hypertension. It needs to be emphasized that the most important variable in
      preventing heart failure is the appropriate treatment of hypertension.

PMID- 15470295
TI  - Treatment of hypertension in the elderly.
AB  - The aging of the United States population means that treatment of hypertension in
      the elderly is becoming an increasingly important issue, and the pathophysiology,
      consequences, and benefits of treatment are quantitatively different in older and
      younger people. There are several issues to be addressed, which include the
      significance of pulse pressure as a risk factor, the reliability of measurement
      of blood pressure in the elderly, choice of drugs and lifestyles, and management
      of the very old.

PMID- 15470296
TI  - Hypertension, renal disease, and drug considerations.
AB  - The incidence of chronic kidney disease is steadily increasing in the United
      States. The magnitude of this problem is such that virtually all health care
      providers are being called upon to manage these patients. The interplay between
      chronic kidney disease and drug therapy is complex in that the kidney is both a
      target for drug effect as well as a moderator of drug elimination. Renal drug
      elimination occurs by filtration, secretion, and/or metabolism. For renally
      cleared compounds, drug clearance typically falls in tandem with the loss of
      renal function. This process is noteworthy for drug accumulation when the
      glomerular filtration rate approaches the 30-cc/min range. The kidney is a target
      for drug effect in relationship to blood pressure and protein excretion.
      Angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy
      (usually given along with a diuretic) are the drug classes that have been shown
      to be effective for reduction in both blood pressure and protein excretion in the
      chronic kidney disease patient. A number of questions still remain unanswered in
      the pharmacotherapy of chronic kidney disease, including the optimal dose for
      these drugs as well as what represents the most favorable achieved blood
      pressure.

PMID- 15470297
TI  - Prevalence of sleep disordered breathing in a heart failure program.
AB  - Recent data show that a high percentage of patients with systolic left
      ventricular dysfunction have sleep-disordered breathing (SDB), contributing to
      the incidence of morbidity and mortality in heart failure. This study examines
      the prevalence of sleep disorders in stable heart failure patients regardless of
      ejection fraction. On three consecutive days in a heart failure clinic, all
      patients were asked to participate in a screening for SDB. This screening
      involved the placement of an outpatient device (ClearPath, Nexan, Inc.,
      Alpharetta, GA), which collects thoracic impedance, oxyhemoglobin saturation, and
      2-lead electrocardiogram data. Sixteen patients (42%) had moderate or severe SDB,
      and 22 patients (55%) had mild or no significant SDB. Fourteen of the 16 patients
      with moderate or severe SDB subsequently received treatment by confirming SDB and
      the continuous positive airway pressure in a sleep lab. Forty-two percent of
      patients with stable heart failure presenting to a heart failure clinic screened
      positive for SDB, despite receiving optimal standard of care.

PMID- 15470298
TI  - Usefulness of B-type natriuretic peptide as a predictor of treatment outcome in
      pulmonary arterial hypertension.
AB  - We examined the utility of early modulation B-type natriuretic peptide (BNP)
      levels in 20 pulmonary arterial hypertension patients as a marker of response to
      epoprostenol therapy. The baseline BNP level was 828+/-217 pg/mL. A total of 19
      hospitalizations and one death occurred in nine patients during 11.0+/-1.8
      months. At baseline, a trend toward higher BNP level was observed among the event
      free (Group A) as compared with clinical event patients (Group B) (1090+/-372 vs.
      510+/-235 pg/mL, respectively; p=0.08). After 3 months on epoprostenol, a
      significant reduction among Group A occurred while Group B demonstrated an
      increase (288+/-92 vs. 610+/-121 pg/mL, p=0.04). A comparison of percent
      reduction in BNP level demonstrated a -70+/-7% change among Group A and an 11+/
      19% increase in Group B (p=0.005). A decrease in BNP level of > or =50% during
      the first 3 months on epoprostenol was strongly predictive of event-free survival
      (p=0.003). This investigation establishes the utility of BNP for predicting
      response to epoprostenol therapy in pulmonary arterial hypertension.

PMID- 15470299
TI  - Quality of life in bridge-to-transplant patients with chronic heart failure after
      implantation of an axial flow ventricular assist device.
AB  - Research suggests that ventricular assist devices improve quality of life for
      congestive heart failure patients awaiting heart transplantation. Axial flow
      ventricular assist devices like the Jarvik 2000 (Jarvik Heart, Inc., New York,
      NY) represent the newest type of ventricular assist device technology, but their
      effects on quality of life are not well understood. Therefore, the authors
      administered the Minnesota Living with Heart Failure Questionnaire to patients
      who had the Jarvik 2000 implanted as a bridge to heart transplantation. Patients
      completed the Minnesota Living with Heart Failure Questionnaire immediately
      before device implantation, 1 month after implantation, immediately before heart
      transplantation, and 1 month after transplantation. One month after implantation
      of the device, the nine patients who completed the study showed significant
      improvements in physical (p<0.008), emotional (p<0.02), and overall (p<0.008)
      quality of life. These improvements were maintained until the device was
      explanted. The authors conclude that implantation of the Jarvik 2000 ventricular
      assist device can substantially improve quality of life for patients awaiting
      heart transplantation.

PMID- 15470300
TI  - Decompensated heart failure: is there a role for the outpatient use of
      nesiritide?
AB  - Heart failure (HF) management has seen enormous advances in the past two decades,
      including publication of HF management guidelines targeted at further reduction
      of morbidity and mortality. Nonetheless, the morbidity of HF has steadily
      increased and now represents one of the largest health care expenditures in this
      country. Because hospitalization for HF is most likely for patients with more
      advanced HF, they share a disproportionate burden of the hospitalization costs
      and will require treatment regimens beyond the current guidelines, if this burden
      is to be alleviated. In June 2004, a group of investigators who helped establish
      the natriuretic peptide treatment paradigm, met to discuss the potential role of
      nesiritide as an outpatient treatment option for patients with symptomatic HF who
      were at high risk for repeated admissions, a syndrome now described as "chronic
      decompensated HF." This report presents their considerations on the contribution
      of natriuretic peptide physiology to the amelioration of progressive left
      ventricular dysfunction, the therapeutic use of B-type natriuretic peptide, and
      its potential application to the outpatient management of acute and chronic
      decompensated HF. The use of outpatient IV nesiritide was considered a promising
      treatment option for symptomatic chronic decompensated HF patients that merits
      further investigation. Such an approach, once validated, should be integrated
      into an evidence-based HF disease management program.

PMID- 15470301
TI  - Endothelial dysfunction and nitric oxide enhancing therapy: a new approach to the
      treatment of heart failure.
AB  - Despite ethnic differences in heart failure prevalence, risk profiles, and
      outcomes, no clinical trials have been designed to prospectively examine the
      mechanisms responsible for these differences. The African-American Heart Failure
      Trial is the first prospective trial designed to test a novel therapy that
      enhances endothelial function and nitric oxide bioavailability in African
      American patients with advanced heart failure.

PMID- 15470302
TI  - Mechanisms and treatment of anemia in chronic heart failure.
AB  - Anemia is highly prevalent in patients with chronic heart failure (HF) and is
      associated with poor clinical outcomes. Multiple mechanisms contribute to anemia
      in chronic HF, and subnormal compensatory rise in endogenous erythropoietin
      levels in response to anemia is one contributory factor. Randomized trials with
      recombinant human erythropoietin therapy in anemic patients with chronic kidney
      disease and concomitant heart disease have demonstrated a reduction in left
      ventricular hypertrophy but variable effects on clinical outcome. Preliminary
      clinical trials in anemic patients with chronic HF demonstrate that
      erythropoietin therapy is well tolerated and associated with short-term clinical
      improvement. The optimum target hemoglobin, erythropoietic agent, and dosing
      regimen, and the role of iron supplementation in patients with chronic HF, are
      not known. Additional studies are needed to determine the safety and efficacy of
      long-term erythropoietic therapy in chronic HF patients.

PMID- 15470303
TI  - Surgical ventricular restoration: technique and outcomes.
AB  - Surgical ventricular restoration is a surgical procedure developed in an attempt
      to reverse the negative remodeling that occurs following myocardial infarction.
      The goal of the procedure is to: 1) reduce the size and restore the normal
      elliptical shape of the heart; 2) perform a complete myocardial
      revascularization; and 3) repair any mitral insufficiency. This article will
      review the surgical procedure and describe outcomes achieved with surgical
      ventricular restoration.

PMID- 15470304
TI  - CHF: "compressive" heart failure? A clinical review of metastatic cardiac tumors.
AB  - Nearly 10% of patients with malignant neoplasms are found to have cardiac
      metastasis. Metastatic disease is much more common than primary cardiac tumors
      and is also associated with a worse prognosis. The authors describe a case of
      mitral inflow obstruction due to metastatic malignancy to the left atrium which
      led to "compressive" heart failure. They further provide a clinical review of
      malignant metastatic heart disease.

PMID- 15470306
TI  - Pharmacotherapy in congestive heart failure: aldosterone receptor antagonism:
      interface with hyperkalemia in heart failure.
AB  - Aldosterone receptor antagonism (ARA) is an increasingly well-accepted element of
      heart failure therapy. The experimental underpinnings for the use of ARA in heart
      failure are strong being linked to a variety of tissue-based cardiac effects
      characteristic of drugs in this class. However, the benefits of ARA therapy do
      not come without some risk since drugs in this class are potent inhibitors of
      renal potassium (K+) elimination. Thus, some increment in serum K+, up to and
      including the development of overt hyperkalemia (typically defined as a serum K+
      value in excess of 6.0 mEq/L), is to be expected whenever they are used.
      Hyperkalemia attributable to ARA relates to several factors including ARA dose,
      patient predisposition to hyperkalemia, as in the case of renal failure, and
      dietary intake of K+. The risk of some change in serum K+ with ARA should not be
      a deterrent to use of drugs in this class but, rather should prompt careful
      surveillance for the onset of this potentially life-threatening electrolyte
      disturbance. The frequency of such scrutiny should be patient-specific and based
      on the constellation of risk factors for hyperkalemia.

PMID- 15470307
TI  - The effects of rest interval length and training on quadriceps femoris muscle.
      Part I: knee extensor torque and muscle fatigue.
AB  - AIM: The purpose of this study was to examine the effects of rest interval on
      quadriceps femoris (QF) muscle strength and fatigue during short-term, high
      intensity training. METHODS: Fifteen healthy males were assessed for isokinetic
      QF strength, via peak torque (PT), work (WK) and power (PW), at a pre-set angular
      velocity of 180 deg x s(-1). Quadriceps femoris muscle fatigue was evaluated as
      the decline in isokinetic work and power (slope) across 30 maximal concentric
      contractions. Subjects were randomly assigned to 1 of 3 groups: Group 1 (short
      rest interval), Group 2 (long rest interval), and Group 3 (control-no training).
      Subjects in Group 1 received a rest period of 40 s in between exercise sets
      corresponding to a 2:1 rest:work ratio. Subjects in Group 2 received a rest
      period of 160 s corresponding to an 8:1 rest:work ratio. Groups 1 and 2 performed
      isokinetic knee extension contractions at 180 deg x s(-1) 2 days per week for 6
      weeks. RESULTS: The results demonstrated a significant increase in QF muscle PT
      across the 6 week training period in the long rest interval group, and no
      significant changes in the short rest interval and control groups. Quadriceps
      femoris muscle work and power were observed to not change significantly across
      the training period in all 3 groups. The reduction in QF muscle work across the
      single set of 30 repetitions was observed to decrease significantly in the
      control group across the 6 week duration; no other significant changes in QF
      muscle fatigue for work and power were observed. CONCLUSION: The major findings
      of this study suggests that the possibility of different physiological mechanisms
      of adaptation exist for QF muscle peak torque, work and power, while changes in
      muscle fatigue resistance may be present when assessed across multiple, rather
      than a single, bouts of activity.

PMID- 15470308
TI  - Concentric quadriceps and hamstrings isokinetic strength in volleyball and soccer
      players.
AB  - AIM: Muscular strength is one of the most important components of sport, both for
      high performance and for injury prevention. One of the most used methods to
      assess strength muscle balance between dominant (D)/non-dominant (ND) and
      antagonist/agonist is isokinetic testing. The main purpose of the present study
      was to describe and to compare isokinetic strength profiles (peak torque,
      bilateral strength differences between D/ND leg (BD) and hamstrings/quadriceps
      (H/Q) ratio) in athletes of different sports and positional roles. METHODS:
      Twenty-eight elite volleyball players and 47 pro soccer players (goalkeepers, n =
      5; full-backs, n = 7; defenders, n = 10; midfielders, n = 15; forwards, n = 10)
      were evaluated using an isokinetic dynamometer (Biodex-System 2). Maximal gravity
      corrected concentric peak torque of knee extensor and flexor muscles were
      measured at angular velocities of 360 degrees x s(-1) (6.28 rad x s(-1)) and 90
      degrees x s(-1) (1.57 rad x s(-1)). RESULTS: No significant BD were found between
      soccer and volleyball players with exception of hamstrings at 90 degrees x s(-1)
      (soccer: 10.6 +/- 8.0% vs volleyball: 6.9 +/- 5.5%). The H/Q ratio was
      significantly lower in volleyball players at 90 degrees x s(-1) (D: soccer 57.4
      +/- 6.7% vs volleyball 50.4 +/- 7.2%; ND: soccer: 56.1 +/- 8.2% vs volleyball:
      50.5 +/- 6.4%). No significant differences were found for BD and H/Q ratio in
      soccer players of different positional roles. CONCLUSION: In general, soccer and
      volleyball players do not seem to be different concerning BD although a
      significant difference was observed in hamstrings at 90 degrees x s(-1).
      Moreover, our data suggest that specific demands of these sports and the
      different positional roles in soccer did not induce bilateral leg imbalances.
      However, sport demands seem to influence isokinetic concentric H/Q ratio.

PMID- 15470309
TI  - Snatch lift kinematics and bar energetics in male adolescent and adult
      weightlifters.
AB  - AIM: The aim of the present study was compare linear kinematics and energy
      changes of the barbell, along with the angular kinematics of the leg movement
      during the snatch technique, between male adolescent and adult weightlifters.
      METHODS: Two S-VHS cameras operating at 60 fields per second recorded the
      heaviest lifts of 14 male adolescent and 9 adult top-level weightlifters under
      competitive conditions. The spatial co-ordinates of selected points on the body
      and the barbell were calculated using the direct linear transformation procedure.
      A low pass digital filter with 4 Hz cut-off frequency was used for the smoothing
      of raw co-ordinate data. The ''t''-test for independent samples was used for the
      statistical treatment of data. RESULTS: The results revealed that there were no
      significant differences between the adolescent and the adult weightlifters in the
      majority of the kinematic variables. However, adolescent weightlifters extended
      their knees significantly slower (t21 = 4.211, p < 0.05) during the 1st pull and
      their ankles during the 2nd pull (t21 = 2.440, p < 0.05) than the adult
      weightlifters did. Moreover, the average relative power output was significantly
      greater for the adult weightlifters during both the 1st (t21 = 2.303, p < 0.05)
      and the snd pull (t21 = 2.611, p < 0.05). CONCLUSION: These results indicate that
      the adolescent weightlifters were characterised from a high level of snatch
      technique and differentiated from the adults predominantly at the less powerful
      execution of the movement.

PMID- 15470310
TI  - Validation of a single-day maximal lactate steady state assessment protocol.
AB  - AIM: The classical maximal lactate steady state (MLSS) assessment protocol takes
      multiple days to measure thus necessitates athletes to return to a laboratory for
      several visits. The purpose of this study was to assess the validity and
      reliability of a new protocol (Palmer protocol), which proposes to measure MLSS
      in a single-day. METHODS: Nine endurance-trained males (age 21.1 +/- 1.6 years,
      VO2max of 63.2 +/- 3.2 ml x kg(-1) x min(-1)) performed the Palmer protocol and
      the classical MLSS assessment protocol. The classical MLSS protocol consisted of
      several constant-velocity runs of increasing intensity. The MLSS was defined as
      the highest velocity associated with an increase in blood lactate concentration
      ([La-]) = or < 1.0 mmol x L (-1) during the final 20 min of a 30 min run.
      Concurrent validity was assessed by calculating a Pearson product correlation
      coefficient between the running velocity at MLSS from the classical protocol and
      from the single-day Palmer protocol. Test-retest reliability was assessed by
      calculating a Pearson product correlation coefficient between the running
      velocities from 2 separate trials of the single-day Palmer protocol. RESULTS: The
      velocity at MLSS from the single-day Palmer protocol (236.4 +/- 27.8 m x min(-1))
      produced a strong correlation of 0.97 (p<0.001) with the velocity at MLSS from
      the classical protocol (226.3 +/- 22.6 m x min(-1)). An equally strong
      correlation was calculated from test-retest reliability of the single-day Palmer
      protocol (r=0.97), (p<0.001). CONCLUSION: These results suggest that the single
      day Palmer protocol is valid and reliable in the estimation of MLSS.

PMID- 15470311
TI  - Physiological changes following a 12 week gym based stair-climbing, elliptical
      trainer and treadmill running program in females.
AB  - AIM: Despite the growing popularity in recent years of the elliptical trainer
      aerobic exercise modality the physiological changes induced following a training
      program using elliptical trainers remains unknown. The present study investigated
      the metabolic and cardiorespiratory improvements following a 12-week aerobic
      training program using elliptical trainer, treadmill or stair-climbing
      modalities. METHODS: Twenty-two moderately active females (28.6 +/- 5.3 y, 1.65
      +/- 0.05 m) were randomly assigned to treadmill running (n=7), elliptical trainer
      (n=8) or stair-climber (n=7) groups and trained 3 days x week(-1) initially at 70
      80% of maximum heart rate (HRmax) for 30 min, progressing to 80-90% HRmax for 40
      min. Subjects performed incremental exercise to volitional exhaustion using an
      electronically loaded cycle ergometer before and upon completion of the program.
      In addition, subjects performed sub-maximal fixed load tests at 0, 4, 8 and 12
      weeks, using ergometers specific to their exercise group. RESULTS: No significant
      inter-group differences were recorded for pre-training VO2max or VEmax.
      Significant (p<0.05) post-training increases in cycling VO2max and VEmax were
      observed for treadmill (mean +/- SEM, 40.7 +/- 2.2 vs 43.4 +/- 2.6 ml x kg(-1) x
      min(-1) and 82.9 +/- 5.1 vs 90.2 +/- 6.4 l x min(-1)), elliptical trainer (36.9
      +/- 2.5 vs 39.6 +/- 2.4 ml x kg(-1) x min(-1) and 86.8 +/- 2.3 vs 92.5 +/- 4.1 l
      x min(-1)) and stair-climber (37.4 +/- 2.9 vs 39.2 +/- 3.1 ml x kg(-1) x min(-1)
      and 95.9 +/- 5.8 vs 97.4 +/- 5.8 l x min(-1)) modalities, however, the increases
      were not significantly different between groups. For all groups, sub-maximal HR
      significantly decreased from week 0 to 4, and from week 4 to 8. CONCLUSION: In
      moderately active females similar physiological improvements were observed using
      stair-climber, elliptical trainer and treadmill running when training volume and
      intensity were equivalent.

PMID- 15470312
TI  - A perceptive individual time trial performed by triathletes to estimate the
      anaerobic threshold. A preliminary study.
AB  - AIM: The aim of the study was to test the ability to estimate the power output
      (PO) and heart rate (HR) associated with ''anaerobic threshold'' levels for
      triathletes by means of a 30-min perceptive individual time trial (PITT30).
      METHODS: Thirteen triathletes (8 males and 5 females) performed an incremental
      exercise test to estimate maximal parameters such as oxygen uptake, power output
      and heart rate. From this incremental exercise test, the individual anaerobic
      threshold (IAT) and ventilatory threshold (VT) for all subjects were estimated.
      Then, the subjects completed a PITT30 at self-selected work intensity on a
      stationary ergometer equipped with the SRM Training System. Mean values of PO,
      HR, and pedalling cadence were recorded continuously between the 5th and the 30th
      min of the test. RESULTS: Significant correlations were observed between the mean
      PO recorded during PITT30 and PO measured at IAT (r=0.88; p<0.0001) and at VT
      (r=0.89; p<0.0001). Furthermore, bias and limits of agreement confirm the degree
      of association between the 3 METHODS: However, PITT30 over-estimated HR values
      compared to the values obtained at IAT and VT. CONCLUSION: It was concluded that,
      for triathletes, mean PO measured with PITT30 allows a partial valid estimation
      of PO associated with 2 known methods of ''anaerobic threshold'' determination.
      The application of PITT30 may offer a useful tool for athletes and coaches to
      estimate the ''anaerobic threshold'' in order to control accurately the training
      effects.

PMID- 15470313
TI  - Physiological and technical characteristics of elite young basketball players.
AB  - AIM: The aim of this study was 2-fold: a) to describe the physiological and
      technical characteristics of elite young basketball players, and b) to examine
      the relationship between certain field and laboratory tests among these players.
      METHODS: Thirteen male players of the junior's Basketball National team (age:
      18.5 +/- 0.5 years, mass: 95.5 +/- 8.8 kg, height: 199.5 +/- 6.2 cm, body fat:
      11.4 +/- 1.9%, means+/-SD) performed a run to exhaustion on the treadmill, the
      Wingate test and 2 types of vertical jump. On a separate day, the field tests
      (control dribble, defensive movement, speed dribble, speed running, shuttle run
      and dribble shuttle run) were conducted. RESULTS: Maximal oxygen uptake (VO2max)
      and ventilatory threshold were 51.7 +/- 4.8 ml/kg/min and 77.6 +/- 7.0% VO2max,
      respectively. Maximum power output was 10.7 +/- 1.3 Watts/kg and mean power
      (Pmean) 8.0 +/- 0.7 Watts/kg. Counter-movement and squat jump height were 40.1 +/
      3.7 and 39.8 +/- 4.0 cm, respectively. Performance in control dribble (13.70 +/-
      0.96 s), speed dribble (4.24 +/- 0.75 s), high intensity shuttle run (27.90 +/-
      1.04 s) and dribble shuttle run (29.50 +/- 1.22 s) was correlated with Pmean (r=
      0.58, r=-0.62, r=-0.56 and r=-0.73, respectively, p<0.05). Percent body fat was
      negatively correlated with all the above field tests (r=0.63, r=0.57, r=0.66,
      r=0.65, respectively, p<0.05). CONCLUSION: These players presented a moderate
      VO2max and anaerobic power. The significant correlation between Pmean and certain
      field tests indicates that these tests could be used for the assessment of
      anaerobic capacity of young basketball players.

PMID- 15470314
TI  - Physiologic profile of recreational male and female novice and experienced Tae
      Kwon Do practitioners.
AB  - AIM: Subjects, 28 recreational male and female novice and experienced Tae Kwon Do
      practitioners (age 19-42 years), were examined on 6 physiological parameters:
      body composition (BF%, skinfold measures), flexibility (sit-and-reach and leg
      splits tests), lower and upper-body dynamic muscular strength (leg press and
      bench press), abdominal strength and endurance (1-minute timed, bent-knee sit-ups
      test), lower extremity explosive power (vertical jump-and-reach test), and
      cardiovascular endurance (graded exercise treadmill test). METHODS: Subjects were
      assigned to 1 of the 4 following groups: Tae Kwon Do experienced and trained men
      (MT), Tae Kwon Do experienced and trained women (FT), novice Tae Kwon Do men
      (MN), and novice Tae Kwon Do women (FN). RESULTS: Results of multiple testing
      procedures and comparison across groups indicated that Tae Kwon Do black belts
      were more athletically fit as compared with that of novice Tae Kwon Do
      practitioners of the same sex in spite of the fact that male and female black
      belts were older than their novice counterparts. Experienced Tae Kwon Do subjects
      were stronger as measured by lower body strength and showed better aerobic
      performance capacity as well as lower percent body fat. Additionally, MT subjects
      demonstrated higher flexibility. CONCLUSION: The highly diverse training,
      repeated and continuous use of the legs and arms alone or combined with maximal
      stretching, and high intensity exercise may account for observed differences
      among groups.

PMID- 15470315
TI  - Low-intensity pulsed ultrasound in the conservative treatment of pseudoarthrosis.
AB  - AIM: The management of pseudarthrosis remains a challenge. Several in vivo animal
      and controlled clinical studies have demonstrated that low-intensity pulsed
      ultrasound can influence fracture healing. METHODS: A prospective longitudinal
      design was used. Fifteen patients (12 males and 3 females; mean age 35.5+/-12.9,
      range 18 to 60), all amateur athletes, under treatment for pseudarthrosis at
      different sites (average fracture age: of 336.6+/-60.1 days) were treated with a
      single 20 min daily application of low-intensity pulsed ultrasound (frequency 1.5
      MHz and intensity 30 mW/cm2). All patients underwent clinical examination and
      plain radiography at the beginning of treatment and were followed up clinically
      and radiographically at 4, 8, 12, 16, 20 and 24 weeks until the fracture healed.
      RESULTS: All fractures healed with a mean healing time of 94.7+/-43.8 days.
      CONCLUSION: Low-intensity pulsed ultrasound is effective in the management of
      long standing fracture non-unions. Prospective randomized studies are needed to
      confirm the value of this modality of treatment.

PMID- 15470316
TI  - Cardiac responses to progressive upright exercise in adult male cyclists.
AB  - AIM: Previous investigations have indicated that maximal stroke volume is the
      primary factor which differentiates physiological aerobic fitness (VO2max) in
      endurance athletes from nonathletes. Understanding the pattern of stroke volume
      response to progressive exercise may provide insights into the mechanisms which
      are responsible for this difference. METHODS: Doppler echocardiography was used
      to estimate stroke volume changes with maximal upright cycle exercise in 8 highly
      trained adult cyclists (mean age 30.5+/-1.6 years) and 16 age-matched nontrained
      males. Ventricular dimensions were measured during exercise using 2-dimensional
      echocardiography (parastemal long axis view). Findings were compared to a group
      of untrained adult male subjects. RESULTS: Mean maximal oxygen uptake was 73.7+/
      7.0 and 47.4+/-7.5 ml x kg(-1) x min(-1) in the 2 groups, respectively. Stroke
      volume rose in both the cyclists and nontrained subjects at the onset of exercise
      but then plateaued without significant change to exhaustion. Values for stroke
      index were significantly greater at rest and all levels of exercise in the
      cyclists (maximal 85+/-13 versus 61+/-13 ml x m(-2)). Two dimensional
      echocardiograms during exercise in the cyclists revealed a small initial rise in
      left ventricular end-diastolic dimension and then a small decline, while systolic
      dimension decreased progressively, resulting in a rise in shortening fraction.
      CONCLUSION: These findings are consistent with the concept that determinants of
      stroke volume at rest are most influential in defining differences in maximal
      stroke volume between athletes and nonathletes.

PMID- 15470317
TI  - Stability and convergent validity of the Physical Activity Scale for the Elderly
      (PASE).
AB  - AIM: The purpose of this study was to assess the stability and convergent
      validity of the Physical Activity Scale for the Elderly (PASE) among rural,
      community dwelling elderly persons using Computer Science and Applications, Inc.
      Actigraph Monitors (Actigraph) as the direct criterion measure. METHODS: 
      EXPERIMENTAL DESIGN: a correlational design was employed. SETTING: rural
      community in the United States. PARTICIPANTS: 56 subjects (age=75.7+/-7.9 years)
      who were living independently and volunteered to participate in the study.
      MEASURES: subjects wore an Actigraph monitor during all waking hours for 7
      consecutive days. At the conclusion of the 7 days, each subject met with a
      trained interviewer to complete the PASE questionnaire. Three days later the
      subjects met with the same interviewer to complete the PASE a 2nd time recalling
      their physical activity for the same 7-day period. RESULTS: Actigraph data
      indicated that subjects averaged 168.1+/-76.3 counts x minute(-1) during the 7
      day period. A high intraclass correlation coefficient (r=0.91) was calculated
      between the 1st interview total PASE score (115.97+/-59.91) and the 2nd interview
      total PASE score (115.71+/-50.97). In addition, there was a statistically
      significant Spearman correlation coefficient of 0.43 (p<0.01) between Actigraph
      mean counts x minute(-1) and 1st interview total PASE scores. CONCLUSION: In this
      rural elderly sample, the PASE was a stable instrument with validity indices
      similar to those previously reported in younger, more active, populations.

PMID- 15470318
TI  - Early alterations in serum creatine kinase and total cholesterol following high
      intensity eccentric muscle actions.
AB  - AIM: The purpose of this experiment was to assess the levels of muscle soreness,
      serum total cholesterol (TC) and creatine kinase (CK) in the first 48 hours
      following fatiguing eccentric exercise performed with the triceps brachii.
      METHODS: Eleven untrained male college students performed a total of 50 eccentric
      elbow extensions in 8 sets (6 x 7 and 2 x 4) with a load equal to 85% of their
      maximal concentric elbow extension strength. Isometric elbow extension strength,
      muscle soreness and circumference, and serum CK and TC concentrations were
      measured before, immediately after, and 2, 24 and 48 hours after the exercise.
      RESULTS: Statistically reliable changes in isometric strength, serum CK and TC,
      muscle soreness and upper arm circumference occurred within the first 48 hours
      following eccentric exercise. Serum TC concentrations exhibited a very rapid
      (within 2 hours) reduction from pre-exercise values after eccentric exercise to a
      relatively stable concentration of approximately 85% of baseline. CONCLUSION:
      These results suggest that serum TC concentration may follow the time-course of
      reductions in force generating capacity more closely than other biochemical
      markers of muscle damage.

PMID- 15470319
TI  - Plasma leptin concentrations in lean, physically active males and females in
      relation to body composition and metabolic variables.
AB  - AIM: It is well recognized that plasma leptin levels even adjusted to body fat
      are significantly higher in females than in males. Additionally, physical
      activity irrespectively of sex is known to affect plasma leptin concentrations.
      However, the predictors of plasma leptin levels in males and females
      characterized by similar physical activity were not studied. The aim of the
      present study was to examine the predictors of plasma leptin concentrations in
      male and female physical education students not engaged in any specific sport but
      active due to obligatory studies' program. METHODS: A total of 36 subjects (17
      males and 19 females) volunteered to participate in the study. Fasting blood was
      drawn from the antecubital vein for glucose and insulin determination. Fasting
      insulin resistance index (FIRI) was calculated from insulin and glucose plasma
      levels. Body fat was assessed using bioelectric impendance method (BIA). Pearson
      product-moment correlations between log10 transformed plasma leptin
      concentrations and FIRI, fat mass, percentage of body fat and lean body mass were
      calculated. Multiple regression analysis was performed to find the best model
      predicting plasma leptin levels. RESULTS: In males the only variables affecting
      plasma leptin concentrations were fat mass (r=0.60; p<0.01) and and the
      percentage of body fat (r=0.49; p<0.04). In contrast, in females the best model
      included fat mass, lean body mass and FIRI (adj. R2=0.538; p=0.002). CONCLUSION:
      The results of the current study indicated that the predictors of plasma leptin
      levels markedly differed in physically active males and females. The only
      variable predicting plasma leptin concentrations in both males and females was
      body fatness. In females lean body mass and fasting insulin resistance index
      (FIRI) together with body fatness markedly contributed to the variations in
      plasma leptin concentrations.

PMID- 15470320
TI  - Differences in the cellular and humoral immune system between middle-aged men
      with different intensity and duration of physically training.
AB  - AIM: The effects of acute exercise on immune system and serum magnesium and iron
      have been investigated in recent years. However, data related to the comparisons
      of long-term physical training with different intensity and duration are limited.
      METHODS: The association between long-term physical training and cellular
      (lymphocyte phenotyping) and humoral immune parameters (serum immunoglobulins)
      and serum magnesium and iron values in the middle-aged men was investigated.
      Eleven male master athletes (MA) performing high intensity and long duration
      training, 11 male recreational athletes (RA) performing moderate intensity and
      duration training (>10 years) participated. Eleven male sedentary individuals
      were enrolled as control group (CG). RESULTS: The percentages of total CD3+ T
      cells, CD4+ T helper, CD8+ T suppressor/cytotoxic, CD19+ B cells, natural killer
      cells, HLA-DR+ active T cells and CD4/CD8 ratios did not show any significant
      difference among 3 groups. In MA, VO2max values showed a significant negative
      correlation with CD4+ T helper cells. There were no significant differences among
      MA, RA and CG in terms of IgG, IgA, and IgM concentrations. There was a
      significant correlation between VO2max and IgG in RA. Iron, iron binding capacity
      and ferritin were found similar in all groups, but serum magnesium level in MA
      was significantly lower than RA and CG. CONCLUSION: No exact data to support
      immunosuppression or immunostimulation could be obtained except a significant
      negative correlation between CD4+ T helper cells and VO2max values in MA and a
      positive correlation between serum IgG and VO2max ivalues in RA. These findings
      may be the indirect markers of cellular immune system suppression by intensive
      exercises and stimulation of IgG production by moderate exercises.

PMID- 15470321
TI  - Cerebral cortex activity during supramaximal exhaustive exercise.
AB  - AIM: The purpose of this study was to examine the effect of fatigue resulting
      from supramaximal dynamic exercise on cerebral cortex activity. METHODS: Five
      healthy male subjects (age 24.6+/-0.4 years, body weight 62.9+/-1.1 kg, height
      175.3+/-1.2 cm, and maximal O2 uptake per body mass 48.4+/-1.3 ml/kg/min)
      participated in this study. All subjects performed at 120% of maximal oxygen
      uptake (VO2peak) on a cycle ergometer until reaching a state of volitional
      fatigue. Cerebral oxygenation was measured by near-infrared spectroscopy (NIRS)
      throughout the supramaximal constant exhaustive exercise. RESULTS: The mean
      exercise duration of the subjects was 147.2+/-3.4 s. The peak value of blood
      lactate concentration within 3-10 min after the exercise test was 14.4+/-0.1
      mmol/l. Cerebral oxygenation (8.8+/-1.8 micromol/l) was increased significantly
      during the first minutes of exercise compared with the pre-exercise value
      (p<0.05) and cerebral oxygenation decreased with the passage of time during
      exercise. Cerebral oxygenation at the end of exercise decreased significantly
      compared with the resting value (-29.9+/-3.4 micromol/l, p<0.05). CONCLUSION:
      These findings suggest that the exhaustive exercise induces the decrease of
      cerebral function and that the fatigue resulting from dynamic exercise decreases
      the cerebral cortex activity.

PMID- 15470322
TI  - Smoking during pregnancy--United States, 1990-2002.
AB  - Cigarette smoking during pregnancy adversely affects the health of both mother
      and child. The risk for adverse maternal conditions (e.g., premature rupture of
      membranes, abruptio placentae, and placenta previa) and poor pregnancy outcomes
      (e.g., neonatal mortality and stillbirth, preterm delivery, and sudden infant
      death syndrome) is increased by maternal smoking. Infants born to mothers who
      smoke weigh less than other infants, and low birthweight (<2,500 grams) is a key
      predictor for infant mortality. Infertility and conception delay also might be
      elevated by smoking. National health objectives for 2010 target an increase in
      cessation to 30% among pregnant smokers during the first trimester and abstinence
      from cigarettes by 99% of women giving birth. To assess progress toward these
      goals, CDC analyzed state-specific trends in maternal smoking during 1990-2002 by
      using data collected on birth certificates. This report summarizes the results of
      those analyses, which indicated that whereas participating areas observed a
      significant decline in maternal smoking during the surveillance period, 10 states
      reported recent increases in smoking by pregnant teens. Although the widespread
      public health message to abstain from smoking during pregnancy has helped
      decrease maternal smoking, to reduce prevalence further, implementation of
      additional interventions are required.

PMID- 15470323
TI  - State estimates of neonatal health-care costs associated with maternal smoking-
      United States, 1996.
AB  - Smoking during pregnancy can cause poor outcomes for both the pregnant woman and
      her unborn child and also result in added health-care expenditures. To
      characterize costs by state, CDC analyzed pregnancy risk surveillance and birth
      certificate data to estimate the association between maternal smoking and the
      probability of infant admission to a neonatal intensive care unit (NICU).
      Neonatal health-care costs, in 1996 dollars, were assigned on the basis of data
      from private health insurance claims. This report summarizes the results of that
      analysis, which estimated smoking-attributable neonatal expenditures (SAEs) of
      366 million dollars in the United States in 1996, or 704 dollars per maternal
      smoker, and indicated wide variations in SAEs among states. These costs are
      preventable. States can use these data to justify or support their prevention and
      cessation treatment strategies.

PMID- 15470324
TI  - State-specific trends in chronic kidney failure--United States, 1990-2001.
AB  - Kidney disease is the ninth leading cause of death in the United States.
      Approximately 19 million U.S. adults have chronic kidney disease, and an
      estimated 80,000 persons have chronic kidney failure diagnosed annually. Major
      causes of chronic kidney failure are diabetes mellitus and hypertension, which
      account for approximately 60% of new cases. To assess national and state-specific
      trends in the prevalence of chronic kidney failure during 1990-2001, CDC analyzed
      data from the United States Renal Data System (USRDS). This report summarizes the
      results of that analysis, which indicated that the prevalence of chronic kidney
      failure in the United States increased 104% during 1990-2001. Treating and
      controlling risk factors and screening persons at high risk for chronic kidney
      failure are key steps that health-care providers and public health practitioners
      can take to reverse the upward trend in this disease.

PMID- 15470325
TI  - Carbon monoxide releases and poisonings attributed to underground utility cable
      fires--New York, January 2000-June 2004.
AB  - Carbon monoxide (CO) is a potentially deadly gas that is odorless, colorless,
      tasteless, and nonirritating. Each year, CO poisoning causes approximately 500
      unintentional deaths in the United States. CO is generated during the incomplete
      combustion of carbon-based fuels such as oil, natural gas, kerosene, coal,
      charcoal, gasoline, and wood. Common sources of CO poisonings include furnaces,
      generators, and nonelectric space heaters. Another potential cause of CO
      poisonings is the unintentional burning of underground utility cables. The oxygen
      poor environment below ground promotes incomplete combustion and the production
      of CO. The New York State Department of Health (NYSDOH) documented 234 events
      during January 2000-June 2004 in which CO releases resulted from underground
      utility cable fires (also known as CO burnout events). This report describes
      these events, summarizes data on reported CO burnouts, and discusses associated
      injuries. The findings underscore the need for preventive actions, such as
      installation of CO detectors in central locations in homes and businesses. In
      homes, CO detectors should be installed outside of each separate sleeping area.

PMID- 15470326
TI  - West Nile virus activity--United States, September 29-October 5, 2004.
AB  - During September 29-October 5, a total of 81 cases of human West Nile virus (WNV)
      illness were reported from 18 states (Alabama, Arizona, Arkansas, California,
      Florida, Georgia, Illinois, Iowa, Kansas, Kentucky, Minnesota, Missouri, Ohio,
      Oklahoma, Pennsylvania, South Dakota, Texas, and Virginia).

PMID- 15470327
TI  - Discovering adverse reactions: why does it take so long?

PMID- 15470328
TI  - Different dosage regimens of rabeprazole for nocturnal gastric acid inhibition in
      relation to cytochrome P450 2C19 genotype status.
AB  - OBJECTIVE: For the treatment of gastroesophageal reflux disease, intragastric pH
      should be lower than 4.0 for no more than 4 hours a day (<16.7%). We aimed to
      develop optimal dosage regimens for rabeprazole to control nocturnal acidity in
      relation to cytochrome P450 (CYP) 2C19 genotypes. METHODS: Fifteen Helicobacter
      pylori -negative volunteers, comprising 5 homozygous extensive metabolizers
      (EMs), 6 heterozygous EMs, and 4 poor metabolizers (PMs) of CYP2C19, took placebo
      and rabeprazole, at a dose of 20 or 40 mg once daily (at 10 pm ) for 8 days.
      Plasma rabeprazole concentrations and 24-hour intragastric pH were determined on
      days 7 and 8, respectively. Because the nocturnal intragastric pH was lower than
      4.0 for more than 16.7% of the time with once-daily regimens in homozygous EMs
      and heterozygous EMs, they were administered 20 mg rabeprazole twice daily (8 am
      and 10 pm ) or 10 mg rabeprazole 4 times daily (8 am , 12:30 pm , 6 pm , and 10
      pm ). RESULTS: With 40 mg rabeprazole once daily, the median percent time with
      nocturnal pH lower than 4.0 was less than 16.7% in PMs (9.5% [range, 3.0%-31.1%])
      but not in homozygous EMs (45.3% [range, 29.0%-52.2%]) ( P = .043) and
      heterozygous EMs (41.3% [range, 33.0%-59.0%]) ( P = .043). The mean plasma
      rabeprazole concentrations differed among the different CYP2C19 genotype groups.
      With 20 mg rabeprazole twice daily and 10 mg rabeprazole 4 times daily, the
      median percent times with nocturnal pH lower than 4.0 were 5.0% (range, 0.0%
      42.0%) and 1.0% (range, 5.0%-7.1%) in heterozygous EMs and 62.0% (range, 10.8%
      68.3%) and 14.7% (range, 0.0%-41.7%) in homozygous EMs, respectively, and plasma
      concentrations were sustained longer than with the once-daily regimens.
      CONCLUSIONS: We propose that rabeprazole dosage regimens for sufficient acid
      inhibition are 20 mg once daily for PMs, 20 mg twice daily for heterozygous EMs,
      and 10 mg 4 times daily for homozygous EMs or heterozygous EMs.

PMID- 15470329
TI  - Impact of the ultrarapid metabolizer genotype of cytochrome P450 2D6 on
      metoprolol pharmacokinetics and pharmacodynamics.
AB  - INTRODUCTION: In the treatment of heart failure and hypertension with metoprolol,
      ultrarapid metabolizers (UMs) may not achieve optimal target concentrations with
      recommended doses. We compared metoprolol pharmacokinetics and effects in UMs
      with extensive metabolizers (EMs) and with poor metabolizers (PM) as an
      additional reference group. METHODS: After a single dose of 100 mg metoprolol,
      pharmacokinetics, resting and exercise heart rate, and blood pressure were
      analyzed in relation to the CYP2D6 genotypes. We included 12 UMs, 13 EMs, and 4
      PMs (healthy volunteers). CYP2D6 genotyping covered alleles *1 to *6 , *9 , *10 ,
      *35 , and *41 and the duplications. beta 1 -Adrenergic receptor polymorphisms
      Ser49Gly and Arg389Gly were included as factors possibly interfering with the
      pharmacokinetic-pharmacodynamic relationship of metoprolol. RESULTS: Median total
      metoprolol clearance values were 31, 168, and 367 L/h and median maximum plasma
      concentrations were 260, 118, and 67 microg/L in PMs, EMs, and UMs, respectively
      ( P < .0001). At 6 hours after administration, metoprolol reduced the exercise
      heart rate by median values of 31, 21, and 18 beats/min in PMs, EMs, and UMs,
      respectively ( P = .01). Blood pressure did not significantly differ according to
      CYP2D6 . CONCLUSIONS: A linear relationship between the number of active CYP2D6
      genes and metabolic clearance of metoprolol was found and the the median
      clearances differed by more than 10-fold between the PM and the UM groups.
      Metoprolol pharmacodynamics, however, differed only by less than 2-fold, and
      there was only a marginal difference in metoprolol efficacy on heart rate between
      the EM and UM groups.

PMID- 15470330
TI  - The effect of clarithromycin, fluconazole, and rifabutin on sulfamethoxazole
      hydroxylamine formation in individuals with human immunodeficiency virus
      infection (AACTG 283).
AB  - BACKGROUND: Sulfamethoxazole hydroxylamine formation, in combination with long
      term oxidative stress, is thought to be the cause of high rates of adverse drug
      reactions to sulfamethoxazole in human immunodeficiency virus (HIV)-infected
      subjects. Therefore the goal of this study was to determine the effect of
      fluconazole, clarithromycin, and rifabutin on sulfamethoxazole hydroxylamine
      formation in individuals with HIV-1 infection. METHODS: HIV-1-infected subjects
      (CD4 + count >/=200 cells/mm 3 ) were enrolled in a 2-part (A and B), open-label
      drug interaction study (Adult AIDS Clinical Trial Group [AACTG] 283). In part A
      (n = 9), subjects received cotrimoxazole (1 tablet of 800 mg sulfamethoxazole/160
      mg trimethoprim daily) alone for 2 weeks and then, in a randomly assigned order,
      cotrimoxazole plus either fluconazole (200 mg daily), rifabutin (300 mg daily),
      or fluconazole plus rifabutin, each for a 2-week period. Part B (n = 12) was
      identical to part A except that clarithromycin (500 mg twice daily) was
      substituted for rifabutin. RESULTS: In part A, fluconazole decreased the area
      under the plasma concentration-time curve (AUC), percent of dose excreted in 24
      hour urine, and formation clearance (CL f ) of the hydroxylamine by 37%, 53%, and
      61%, respectively (paired t test, P < .05). Rifabutin increased the AUC, percent
      excreted, and CL f of the hydroxylamine by 55%, 45%, and 53%, respectively ( P <
      .05). Fluconazole plus rifabutin decreased the AUC, percent excreted, and CL f of
      the hydroxylamine by 21%, 37%, and 46%, respectively ( P < .05). In part B the
      fluconazole data were similar to those of part A. Overall, clarithromycin had no
      effect on hydroxylamine production. CONCLUSIONS: If the exposure (AUC) to
      sulfamethoxazole hydroxylamine is predictive of sulfamethoxazole toxicity, then
      rifabutin will increase and clarithromycin plus fluconazole or rifabutin plus
      fluconazole will decrease the rates of adverse reactions to sulfamethoxazole in
      HIV-infected subjects.

PMID- 15470331
TI  - Effect of St John's wort on imatinib mesylate pharmacokinetics.
AB  - OBJECTIVE: Imatinib is a potent inhibitor of the Bcr-Abl and c- kit tyrosine
      kinases and is approved for the treatment of Philadelphia chromosome-positive
      chronic myelogenous leukemia and gastrointestinal stromal tumors. Because
      imatinib is predominantly metabolized by cytochrome P450 (CYP) 3A4, its
      pharmacokinetics may be altered when it is coadministered with drugs or herbs
      (eg, St John's wort) that modulate CYP3A4 activity. Thus we examined the effects
      of St John's wort on imatinib pharmacokinetics. METHODS: This 2-period, open
      label, fixed-sequence study was completed by 12 healthy subjects (6 men and 6
      women) aged between 20 and 51 years. Each subject received 400 mg imatinib orally
      on study day 1, St John's wort (300 mg 3 times daily) on days 4 to 17, and 400 mg
      imatinib again on day 15. Serial blood samples were obtained over a 72-hour
      period after each imatinib dose. Imatinib and N -desmethyl-imatinib (CGP 74588)
      were quantified in plasma by liquid chromatography-mass spectrometry. RESULTS: St
      John's wort administration increased imatinib clearance by 43% ( P < .001), from
      12.5 +/- 3.6 L/h to 17.9 +/- 5.6 L/h; imatinib area under the concentration
      versus time curve (AUC) extrapolated to infinity was decreased by 30%, from 34.5
      +/- 9.5 microg . h/mL to 24.2 +/- 7.0 microg . h/mL ( P < .001). Imatinib half
      life (12.8 hours versus 9.0 hours) and maximum concentration (C max ) (2.2
      microg/mL versus 1.8 microg/mL) were also significantly decreased ( P < .005). N 
      desmethyl-imatinib C max was increased from 285 +/- 95 ng/mL to 318 +/- 95 ng/mL
      during St John's wort dosing, but the AUC from 0 to 72 hours was not altered.
      CONCLUSIONS: These data indicate that St John's wort increases imatinib
      clearance. Thus patients taking imatinib should avoid taking St John's wort.
      Concomitant use of enzyme inducers, including St John's wort, may necessitate an
      increase in the imatinib dose to maintain clinical effectiveness.

PMID- 15470332
TI  - Hyperforin content determines the magnitude of the St John's wort-cyclosporine
      drug interaction.
AB  - OBJECTIVE: Hyperforin (HYF) has been discussed as a potential cause of the
      reduction in the bioavailability of numerous drugs seen with St John's wort (SJW)
      comedication. This study compared the effects of 2 SJW preparations with high and
      low HYF content on the pharmacokinetics of cyclosporine (INN, ciclosporin) (CSA).
      METHODS: In a crossover study, 10 renal transplant patients were randomized into
      2 groups and received SJW extract (900 mg/d) containing low or high
      concentrations of HYF for 14 days in addition to their regular regimen of CSA.
      After a 27-day washout phase, patients were crossed over to the other SJW
      treatment for 14 days. Blood concentrations of CSA were measured by immunoassay.
      RESULTS: The study showed a significant difference between the effects of the 2
      SJW preparations on CSA pharmacokinetics (area under the plasma concentration
      time curve within one dosing interval [AUC 0-12 ], P < .0001, ANOVA). AUC 0-12
      values (monoclonal) with high-HYF SJW comedication were 45% lower (95% confidence
      interval [CI], -37% to -54%; P < .05, Student-Newman-Keuls test) than for low-HYF
      SJW. The dose-corrected AUC 0-12 for CSA (monoclonal) decreased significantly
      compared with baseline by 52% (95% CI, -46% to -56%; P < .05) after 2 weeks of
      comedication with high-HYF SJW. Values of peak concentration in plasma and drug
      concentration at the end of one dosing interval were affected to a similar
      extent, with reductions by 43% (95% CI, -36% to -48%) and 55% (95% CI, -48% to 
      60%), respectively. In addition, a 65% (95% CI, 53% to 85%; P < .05) increase in
      daily CSA doses was required during high-HYF SJW treatment. In contrast,
      coadministration of low-HYF SJW did not significantly affect CSA pharmacokinetics
      and did not require CSA dose adjustments compared with baseline. CONCLUSION: HYF
      content of SJW extracts significantly affects the extent of the pharmacokinetic
      interaction between CSA and SJW.

PMID- 15470333
TI  - In vivo comparisons of constitutive cytochrome P450 3A activity assessed by
      alprazolam, triazolam, and midazolam.
AB  - BACKGROUND: Previous studies have not demonstrated good correlations between
      various presumed phenotypic measures of in vivo cytochrome P450 (CYP) 3A
      activity. However, in reality, few have used appropriate and validated in vivo
      probes that consider the complexities of CYP3A. Accordingly, the disposition of 3
      closely related benzodiazepines with extensive and similar CYP3A-mediated
      metabolism characteristics but different pharmacokinetics was investigated, and
      correlations between the drugs were examined. METHODS: The single-dose oral
      clearances of alprazolam, midazolam, and triazolam and the systemic clearances of
      the latter 2 drugs were separately determined in 21 healthy subjects (10 men)
      according to a randomized experimental design with a minimum 1-week period
      between the individual studies. An erythromycin breath test was also performed.
      RESULTS: After intravenous administration, systemic clearance varied 3-fold
      compared with a 6-fold range in clearance after an oral dose for all 3 drugs.
      However, mean values differed markedly between the drugs, with the systemic
      clearance of midazolam being almost double that of triazolam (383 +/- 73 mL/min
      versus 222 +/- 54 mL/min). Oral clearances were even more dissimilar: alprazolam,
      75 +/- 36 mL/min; triazolam, 360 +/- 195 mL/min; and midazolam, 533 +/- 759
      mL/min. Estimates of CYP3A-mediated extraction by the intestine and liver
      indicated approximately equal contributions by both organs but larger values for
      midazolam than for triazolam, and these differences accounted for the differences
      in oral bioavailability, 30% +/- 13% versus 55% +/- 20%, respectively.
      Statistically significant ( P = .001 to .004) correlations between the 3 drugs'
      oral clearances ranged from 0.60 to 0.68 ( r s value), whereas the correlation
      for the systemic clearances of midazolam and triazolam was 0.66 ( P = .001). No
      statistically significant relationships were observed between any of the
      clearance parameters and the erythromycin breath test. CONCLUSION: Despite
      alprazolam, midazolam, and triazolam having markedly different pharmacokinetic
      characteristics, statistically significant correlations were present between the
      oral and systemic clearances of the 3 drugs, consistent with a major involvement
      of CYP3A in their metabolism and elimination. However, the magnitude of the
      coefficients of determination ( r s ) was such to suggest that an in vivo probe
      approach, even with the use of valid phenotypic trait values, will be unable to
      accurately and reliably predict the pharmacokinetic behavior of another CYP3A
      substrate, as determined by the enzyme's constitutive activity.

PMID- 15470334
TI  - The effects and metabolic fate of nitroflurbiprofen in healthy volunteers.
AB  - OBJECTIVE: Nitric oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs)
      are a new class of cyclooxygenase (COX) inhibitors. To investigate whether these
      drugs actually release nitric oxide (NO), we labeled the nitroxy group of
      nitroflurbiprofen with nitrogen 15 to determine the metabolic fate of this
      compound in humans. METHOD: Six healthy volunteers who fasted were given an oral
      dose of 15 N-nitroflurbiprofen (100 mg). Samples of blood, urine, and gastric
      headspace gas were taken over a 24-hour period to determine the levels of
      nitroflurbiprofen, flurbiprofen, total nitrate/nitrite, 15 N-nitrate/nitrite, COX
      activity, and gastric NO. In a crossover study (1 week apart), a further 6
      healthy volunteers who fasted were given an oral dose of nitroflurbiprofen (100
      mg) or flurbiprofen (65 mg) and levels of gastric NO were determined. RESULTS:
      Nitroflurbiprofen was undetectable in the systemic circulation. Levels of 15 N
      nitrate/nitrite (5.2% +/- 1.5% enrichment) and flurbiprofen (2.4 +/- 0.7
      microg/mL) peaked at 4 hours in the plasma and gradually decreased thereafter. In
      unstimulated blood, the plasma levels of thromboxane B 2 (COX-1 activity) were 2
      to 3 ng/mL, and after calcium ionophore stimulation, large amounts of thromboxane
      B 2 were produced (112 +/- 31 ng/mL). Prostaglandin E 2 was undetectable in
      unstimulated blood. After lipopolysaccharide stimulation, the plasma levels of
      prostaglandin E 2 increased to 15 +/- 4 ng/mL. The metabolite flurbiprofen
      inhibited plasma COX-1 activity for the duration of the study period (maximum
      inhibition at 4 hours), whereas COX-2 activity recovered after 6 hours. In the
      crossover study, levels of gastric NO were higher in subjects given
      nitroflurbiprofen, when compared with those given flurbiprofen. (The area under
      the curve for gastric NO was 435 +/- 107 ppm . h versus 305 +/- 94 ppm . h [95%
      confidence interval of the difference, 89-172 ppm . h; P < .001]). CONCLUSION:
      Nitroflurbiprofen was undetectable in the systemic circulation, suggesting
      metabolism to 15 N-nitrate/nitrite and flurbiprofen in the presystemic
      circulation. Levels of gastric NO were significantly higher after ingestion of
      nitroflurbiprofen than flurbiprofen.

PMID- 15470335
TI  - QT interval prolongation after oxytocin bolus during surgical induced abortion.
AB  - BACKGROUND: Although oxytocin, a uterotonic agent, may cause short-term
      vasodilation that results in severe hypotension, it is still routinely given as
      an intravenous bolus injection during surgical suction curettage. Two reported
      cases of ventricular tachycardia after oxytocin bolus in patients with long QT
      interval syndrome led us to assess the effect of oxytocin on QT interval. METHOD:
      Thirty-eight healthy women scheduled for a surgical suction curettage with
      general anesthesia were enrolled. General anesthesia was induced by propofol and
      maintained by either propofol (n = 18) or sevoflurane (n = 20).
      Electrocardiographic recordings were obtained before and at 1, 2, 3, and 5
      minutes after a 10-U intravenous bolus of oxytocin. RESULTS: Intravenous oxytocin
      induced a pronounced QTc interval prolongation of 41 +/- 21 ms ( P < .0001),
      which was maximal 1 minute after administration. The QTc interval returned to
      control values 3 minutes after oxytocin bolus. Oxytocin bolus also induced an
      increase in heart rate of 19 +/- 10 beats/min and a significant decrease in
      systolic arterial pressure of 11 +/- 9 mm Hg (both P < .0001). The drug used to
      maintain anesthesia was not an independent factor of QT interval prolongation in
      ANOVA analysis. CONCLUSIONS: Oxytocin intravenous bolus induced a large and
      transient QTc interval prolongation, suggesting that it may lead to proarrhythmia
      in circumstances favoring QTc interval increase.

PMID- 15470336
TI  - No adverse hemodynamic interaction between sildenafil and red wine.
AB  - OBJECTIVE: Our objective was to investigate the hemodynamic interaction between
      sildenafil and red wine. Sildenafil citrate (Viagra), a phosphodiesterase type 5
      inhibitor, is an effective treatment for male erectile dysfunction that
      potentiates nitric oxide-mediated vasodilation. Alcohol is a commonly used
      recreational substance with complex vascular effects, which may, in part, be
      mediated by nitric oxide. Thus there is potential for an adverse hemodynamic
      interaction. METHODS: Eight healthy men received either 100 mg sildenafil,
      alcohol (750 mL red wine, 13.5% by volume), or the combination, in a 4-way,
      double placebo-controlled, randomized crossover study. Blood pressure, heart
      rate, and cardiac index were measured every 15 minutes up to 180 minutes.
      RESULTS: Results are expressed as mean +/- SEM. Red wine increased cardiac index
      (by 15% +/- 8%, P = .04) and heart rate (by 27% +/- 5%, P < .0001). Mean arterial
      pressure initially increased by approximately 5% and then fell by a maximum of
      approximately 7%. Sildenafil reduced peripheral vascular resistance (by 24% +/-
      8%, P = .03) and mean arterial pressure (by 7% +/- 3%, P = .03) with no effect on
      cardiac index or heart rate. CONCLUSIONS: There is no clinically important
      hemodynamic interaction between sildenafil and alcohol (red wine).

PMID- 15470337
TI  - Influences of sildenafil on lung function and hemodynamics in patients with
      chronic heart failure.
AB  - BACKGROUND: Chronic heart failure (CHF) may be associated with a disordered
      nitric oxide (NO)-mediated regulation of the pulmonary vessel tone and
      permeability and of the gas transfer across the alveolar-capillary membrane.
      Whether enhancement of NO availability is beneficial with regard to these
      functions has not been explored. Phosphodiesterase 5 inhibitors, such as
      sildenafil, may provide a tool with which to test this possibility. METHODS: In
      10 patients with CHF and 10 normal subjects, before and at 60 minutes after
      sildenafil (50 mg) or placebo, we measured left ventricular ejection fraction,
      pulmonary hemodynamics, lung diffusion capacity for carbon monoxide and its
      alveolar-capillary membrane and blood capillary volume subcomponents, and flow
      mediated brachial artery dilation (FMD) during reactive hyperemia to distal
      circulatory arrest (an indirect index of NO-mediated endothelial function).
      RESULTS: In patients with CHF, sildenafil caused no variations in ejection
      fraction, cardiac index, wedge pulmonary pressure, and blood capillary volume; it
      decreased pulmonary artery systolic (-21.6%) and diastolic (-31.8%) pressure and
      arteriolar resistance (-36.9%); and it increased lung diffusion capacity for
      carbon monoxide (+11.2%), diffusing capacity of the alveolar-capillary membrane
      (+10.6%), and FMD (from +8.3% to +13.4%). All changes were significant at P <
      .01. None of these effects was observed in healthy subjects. Placebo was
      ineffective in both patients and control subjects. CONCLUSION: This study
      provides the novel information that, in patients with CHF, phosphodiesterase 5
      inhibition with sildenafil ameliorates the pulmonary hemodynamics and reduces the
      impedance of the alveolar-capillary interface, even if left ventricular filling
      pressure and function remain steady. The associated improvement in FMD at the
      periphery substantiates the possibility that an enhancement in NO release may
      underlie these effects.

PMID- 15470338
TI  - Angiotensin-converting enzyme inhibition and smoking potentiate the kinin
      response to cardiopulmonary bypass.
AB  - BACKGROUND: This study tested the hypothesis that angiotensin-converting enzyme
      (ACE) inhibitors potentiate activation of the kallikrein-kinin system during
      cardiopulmonary bypass (CPB). METHODS: The effects of CPB on concentrations of
      bradykinin and its metabolite bradykinin 1-5 (BK1-5) were determined in 31
      patients taking an ACE inhibitor who were randomized to continue ACE inhibitors
      until coronary artery bypass surgery (ACE inhibitor group, N = 19) or to
      discontinue them 48 hours before surgery (no ACE inhibitor group, N = 12).
      Arterial and venous blood was sampled before CPB, at 30 minutes of CPB, at 60
      minutes of CPB, after separation from CPB, and on postoperative day 1. RESULTS:
      Arterial bradykinin ( P < .001 [from 22.4 +/- 24.1 fmol/mL to 86.2 +/- 98.7
      fmol/mL in the no ACE inhibitor group]) and arterial ( P < .001) and venous ( P =
      .016) BK1-5 concentrations increased significantly during CPB. Arterial
      bradykinin concentrations were significantly higher ( P = .017), whereas BK1-5
      concentrations ( P = .024) and the molar ratio of BK1-5/bradykinin ( P = .008)
      were significantly lower in the ACE inhibitor group compared with the no ACE
      inhibitor group. In addition, arterial bradykinin concentrations were
      significantly increased in smokers compared with nonsmokers ( P = .015), when we
      controlled for the ACE inhibitor group. There was no effect of smoking on ACE
      activity ( P = .597 overall). There was a significant inverse correlation between
      arterial bradykinin and mean arterial pressure ( r 2 = 0.2137, P = .010) and a
      significant correlation between arterial bradykinin and tissue-type plasminogen
      activator antigen concentrations ( r 2 = 0.174, P = .022) during CPB. Tissue-type
      plasminogen activator antigen was significantly higher in the ACE inhibitor group
      than in the no ACE inhibitor group (18.0 +/- 7.8 ng/mL versus 12.4 +/- 4.5 ng/mL,
      P = .016) but not in smokers compared with nonsmokers ( P = .451). CONCLUSION:
      Preoperative ACE inhibitors and smoking potentiate the kinin response to CPB and
      may contribute to the hemodynamic and fibrinolytic response observed during CPB.

PMID- 15470339
TI  - Substantially elevated levels of atorvastatin and metabolites in cyclosporine
      treated renal transplant recipients.

PMID- 15470340
TI  - Cytochrome P450 3A expression and activity in the human small intestine.

PMID- 15470341
TI  - Take a stand on smoking.

PMID- 15470342
TI  - New diagnostic tools in orthodontics.

PMID- 15470343
TI  - Comparison between traditional 2-dimensional cephalometry and a 3-dimensional
      approach on human dry skulls.
AB  - The cephalogram is the standard used by orthodontists to assess skeletal, dental,
      and soft tissue relationships. This approach, however, is based on 2-dimensional
      (2D) views used to analyze 3-dimensional (3D) objects. The purpose of this
      project was to evaluate and compare a 3D imaging system and traditional 2D
      cephalometry for accuracy in recording the anatomical truth as defined by
      physical measurements with a calibrated caliper. Thirteen skeletal landmarks were
      located by both radiographic methods on 9 dry human skulls. Intraclass
      correlation (0.995), variance (0.054 mm(2)), and standard deviation (SD) (0.237
      mm) were averaged over 76 measurements and derived from precision calipers to
      establish these physical measurements as a reliable gold standard to make
      comparisons of the 2D and 3D radiographic methods. The results showed great
      variability of the 2D from the gold standard, with the range varying from -17.68
      mm (underestimation of Gn-Zyg R) to +15.52 mm (overestimation of Zyg L-Zyg R). In
      contrast, the 3D method (Sculptor, Glendora, Calif) indicated a range of the SD
      from -3.99 (underestimation) mm to +2.96 mm (overestimation). The 3D evaluation
      was much more precise, within approximately 1 mm of the gold standard. These
      results indicate that, when the actual distance is measured on a human skull in
      its true dimensions of 3D space, the Sculptor program, by using a 3D method, is
      more precise and 4 to 5 times more accurate than the 2D approach. Evaluating
      distances in 3D space with a 2D image grossly exaggerates the true measure and
      offers a distorted view of craniofacial growth. There is an inherent problem of
      representing a linear measure occupying a 3D space with a 2D image.

PMID- 15470344
TI  - Three-dimensional changes in the condyle during development of an asymmetrical
      mandible in a rat: a microcomputed tomography study.
AB  - A rapidly growing postnatal animal model was used to study changes in the
      calcified tissue of the mandibular condyle during altered muscle function. A
      maxillary occlusal splint was designed to shift the mandible laterally (left)
      during closure. Groups of 5 Wistar rats were killed at 5, 9, 15, 21, 30, and 40
      weeks (n = 30), with an equal number of controls. The experimental animals
      developed shorter, asymmetrical mandibles compared with the control animals. The
      left condyle became larger and thicker than the right condyle. Microcomputed
      tomography assessment of the left and right condylar trabecular bone indicated
      that both had less bone volume than the control condyle. The right masseter
      muscle significantly lost fiber size and type IIA oxidative fibers, suggesting
      that the right masseter muscle was used with less tension development. In
      contrast, the left masseter maintained its fiber size and was similar to the
      control masseter fiber diameters. Comparison in the sequence of changes indicated
      that the morphologic changes occurred first in the ramus (age, 5 weeks), before
      the corpus (age, 15 weeks), and before changes in masseter fiber size and
      composition (age, 9 weeks). This study showed that both the mandible and the
      condyle modified their shape and size, as well as the trabecular bone of the
      condyle, during shifting of the mandible to one side as it closed.

PMID- 15470345
TI  - Mechanical strain on the human skull in a humanoid robotic model.
AB  - Patterns of strain were analyzed in a dry human skull at 15 different regions on
      the lateral and medial surfaces of the mandible. The strains were induced with a
      human robotic system that represented each of 8 bilateral muscles by a DC
      servomotor connected to a wire and pulley. The tractions of the simulated muscles
      (masseter, medial pterygoid, anterior temporalis, and posterior temporalis) were
      increased from 1x to 4x with each representing different levels of traction or
      force (5, 3, 4, and 4 N, respectively). The study was done with the teeth in
      maximum intercuspal occlusion. Bite forces were also measured with a transducer
      and reached a maximum of 40 N on the posterior teeth with less force on the
      anterior dentition. The smallest traction level (1x) developed some small
      strains. At 2x, compressive strains developed more on the medial (lingual) side
      beneath the molars through the corpus and radiated into the anterior ramus.
      Strains at 3x to 4x significantly increased both the tensile and compressive
      strains throughout the mandible with more strains developing in the ramus. The
      increased bilateral traction and loading developed significant compressive forces
      on both sides of the mandible. Evaluation of disparities between compressive and
      tensile strains at one site, and comparison between the medial and lateral sides
      of strain, suggested some visible distortion of portions of the mandible under
      the higher loads.

PMID- 15470346
TI  - Delayed tooth eruption: pathogenesis, diagnosis, and treatment. A literature
      review.
AB  - Delayed tooth eruption (DTE) is the emergence of a tooth into the oral cavity at
      a time that deviates significantly from norms established for different races,
      ethnicities, and sexes. This article reviews the local and systemic conditions
      under which DTE has been reported to occur. The terminology related to
      disturbances in tooth eruption is also reviewed and clarified. A diagnostic
      algorithm is proposed to aid the clinician in the diagnosis and treatment
      planning of DTE. The sequential and timely eruption of teeth is critical to the
      timing of treatment and the selection of an orthodontic treatment modality. This
      review addresses the need for a more in-depth understanding of the underlying
      pathophysiology of DTE and gives the clinician a methodology to approach its
      diagnosis and treatment.

PMID- 15470347
TI  - Performance measures to improve the quality of orthodontic services and control
      expenditures.
AB  - One of the most critical and contentious issues for specialist and nonspecialist
      professionals in the coming decades will be to evaluate the outcomes of health
      care services. Performance measures are imperative for elective orthodontics,
      because of the relatively weak evidence that they lead to significant
      improvements in dental and oral health, occlusal function, and psychological well
      being of patients. Such measures are particularly crucial for orthodontic
      treatment eligible for benefit payments, because they will assure third-party
      dental insurers that the annual premiums levied from governments (taxes),
      employers (in lieu of salary increments), and individuals (in lieu of other
      discretionary expenditures) are well spent (ie, not wasted). Performance measures
      will also improve the "standards of orthodontic practice," so the continued
      integrity of the profession is contingent on their development.

PMID- 15470348
TI  - Dentoskeletal treatment changes in Class II subdivision malocclusions in
      submentovertex and posteroanterior radiographs.
AB  - The objective of this study was to evaluate the dentoskeletal changes consequent
      to orthodontic treatment in subjects with Class II subdivision malocclusions,
      treated with asymmetric extractions, compared with a normal-occlusion control
      group. The sample consisted of 3 groups, with 30 subjects in each: normal
      occlusion subjects (group 1), untreated Class II subdivision subjects (group 2),
      and Class II subdivision patients treated with asymmetric extractions (group 3).
      All subjects had a full complement of permanent teeth at the beginning of
      treatment. The average ages of the subjects were 22.42, 15.76, and 18.57 years,
      respectively, in groups 1, 2, and 3. Measurements of relative differences in the
      spatial position of dental and skeletal bilateral landmarks were obtained from
      the submentovertex and posteroanterior cephalometric (PA) radiographs. The t test
      for independent samples was used to compare group 1 with groups 2 and 3 at
      different times. Results from the submentovertex radiograph showed that
      asymmetric extractions in Class II subdivision malocclusions will maintain the
      differences in the anteroposterior positions of right and left, maxillary and
      mandibular first molars, as would be expected with the treatment protocols used.
      There were no significant skeletal changes that could be attributed to the
      treatment approaches investigated or transverse collateral effects with the
      asymmetric mechanics used. It was also demonstrated that treatment of Class II
      subdivision malocclusions with asymmetric extractions produced corrections of
      maxillary and mandibular dental midline deviations with the midsagittal plane,
      without canting the occlusal plane or any other investigated horizontal plane, as
      seen in the PA radiograph. Treatment of Class II subdivision malocclusions with
      asymmetric extractions constitutes a beneficial approach to this problem.

PMID- 15470349
TI  - Evaluation of dental arch width and form changes after orthodontic treatment and
      retention with a new computerized method.
AB  - The purpose of this study was to evaluate longitudinal arch width and form
      changes and to define arch form types with a new computerized method. Maxillary
      and mandibular models of 21 Class II Division 1 patients were examined before
      treatment (T(0)), after treatment (T(1)), and an average of 3 years after
      retention (T(2)). Arch width measurements were made directly on scanned images of
      maxillary and mandibular models. Arch form changes at T(0)-T(1) and T(1)-T(2)
      were evaluated by superimposing the computer-generated Bezier arch curves with a
      computer program. Types of dental arch forms were defined by superimposing them
      with the pentamorphic arch system, which included 5 different types of arch
      forms: normal, ovoid, tapered, narrow ovoid, and narrow tapered. Maxillary arch
      widths were increased during orthodontic treatment. Mandibular posterior arch
      widths were also increased. The expansion of the mandibular arch forms was less
      than in the maxillary arch forms. Arch width changes were generally stable,
      except for reduction in maxillary and mandibular interlateral, inter-first
      premolar, and mandibular intercanine widths. Pretreatment maxillary arch forms
      were mostly tapered; mandibular arch forms were tapered and narrow tapered. In
      maxillary arch forms, 76% of the treatment changes were maintained. Mandibular
      arch form was maintained in 67% of the sample, both during treatment and after
      retention. In mandibular arches, 71% of orthodontically induced arch form changes
      were maintained.

PMID- 15470351
TI  - Accuracy of third-order bends of nickel-titanium wires and the effect of high and
      low pressure during memorizing heat treatment.
AB  - This study evaluated the accuracy of third-order bends of nickel-titanium wires
      and determined the effect of high and low pressure for maintaining the wire shape
      during memorizing heat treatment. A computer-aided bending machine was used to
      incorporate 200 randomly determined torsional angles between 0 degrees and 60
      degrees into 30 linear 0.016 x 0.022-in NeoSentalloy F80 (GAC International,
      Central Islip, NY) wires. The torsional bendings were randomized into 2 groups.
      Bends assigned to group 1 (n = 100) received heat treatment of 1.6 MPa (16 bar)
      pressure, and bends assigned to group 2 (n = 100) received heat treatment of 50
      MPa (500 bar) pressure. Cross-sectional cuts from the bent wires were prepared by
      using standard metallurgical techniques, and the torsional angles were analyzed
      under computer control. The results of our study show that third-order bends </=
      30 degrees can be made with adequate clinical accuracy with an error of 1.89
      degrees +/- 1.75 degrees (0 degrees to 10 degrees ) and 3.57 degrees +/- 1.57
      degrees (20 degrees to 30 degrees ), irrespective of the pressure applied. With
      bends > 30 degrees but </= 40 degrees , the method with the higher pressure
      offers fundamentally greater precision than that with the lower pressure. With
      torque bends > 40 degrees , the bending error with both methods is clinically
      unacceptable. In addition to the variability in the dimension and composition of
      nickel-titanium wires, the scale of the incorporated plastic deformations makes a
      substantial contribution to the bending error. As far as permitted by the
      clinical situation, then, the bend should be distributed over the maximum
      possible wire length. Third-order bends in the first rectangular pseudoelastic
      nickel-titanium wires represent an efficient means of effecting torque at an
      early stage. This individualization allows the full therapeutic potential of
      these archwires to be exploited right from the initial phase of treatment.

PMID- 15470352
TI  - Cephalometric keys to internal derangement of temporomandibular joint in women
      with Class II malocclusions.
AB  - The aim of this study was to find cephalometric keys to provide information on
      the progression of temporomandibular internal derangement. The sample consisted
      of 58 women with Class II malocclusions. They were examined with routine lateral
      cephalograms and magnetic resonance imaging of the temporomandibular joint (TMJ)
      before orthodontic treatment. They were classified into 3 groups according to the
      results of the magnetic resonance imaging: normal disk position, disk
      displacement with reduction, and disk displacement without reduction. Thirty-four
      cephalometric variables regarding their pretreatment lateral cephalograms were
      analyzed by 1-way analysis of variance to evaluate the differences in the
      dentofacial morphology among the 3 groups. The results showed a decrease in
      posterior facial height, a decrease in ramus height, and backward rotation and
      retruded position of the mandible in the subjects with internal derangement of
      the TMJ. These changes were less severe in those with disk displacement with
      reduction and more severe as internal derangement progressed to disk displacement
      without reduction. The results suggest that internal derangement of the TMJ might
      induce dentofacial changes, and that some cephalometric variables can assist in
      identifying potential patients with internal derangement of the TMJ.

PMID- 15470354
TI  - Long-term outcome in a patient with Class I malocclusion with severe crowding
      treated without extractions.
AB  - The treatment of a patient with a Class I malocclusion with significant skeletal
      transverse maxillary discrepancy and severe crowding is presented. The maxilla
      was narrow compared with the mandible, and the posterior teeth were compensated,
      with the maxillary teeth inclined buccally and the mandibular teeth inclined
      lingually. Treatment included rapid palatal expansion to correct the transverse
      maxillary deficiency and to gain arch length. Long-term follow-up (20 years) with
      a stable result is reported.

PMID- 15470355
TI  - Category 1: Interceptive or early treatment.
AB  - This case report was part of a display of cases sponsored by the American Board
      of Orthodontics after the board-certification process. The summary of treatment
      and records are reprinted here as they were submitted to the board.

PMID- 15470356
TI  - How can I match the color on 2 intraoral digital images?

PMID- 15470357
TI  - Litigation, legislation, and ethics. Truth or consequences: lies-representations
      or warranties?

PMID- 15470358
TI  - The role of part-time educators in defining knowledge and skill levels in
      orthodontic residency programs.

PMID- 15470359
TI  - Subcellular distribution of HP1 proteins is altered in ICF syndrome.
AB  - The Immunodeficiency, Centromeric instability, and Facial (ICF) syndrome is a
      rare autosomal recessive disorder that results from mutations in the DNMT3B gene,
      encoding a DNA-methyltransferase that acts on GC-rich satellite DNAs. This
      syndrome is characterized by immunodeficiency, facial dysmorphy, mental
      retardation of variable severity and chromosomal abnormalities that essentially
      involve juxtacentromeric heterochromatin of chromosomes 1 and 16. These
      abnormalities demonstrate that hypomethylation of satellite DNA can induce
      alterations in the structure of heterochromatin. In order to investigate the
      effect of DNA hypomethylation on heterochromatin organization, we analyzed the in
      vivo distribution of HP1 proteins, essential components of heterochromatin, in
      three ICF patients. We observed that, in a large proportion of ICF G2 nuclei, all
      HP1 isoforms show an aberrant signal concentrated into a prominent bright focus
      that co-localizes with the undercondensed 1qh or 16qh heterochromatin. We found
      that SP100, SUMO-1 and other proteins from the promyelocytic leukemia nuclear
      bodies (NBs) form a large body that co-localizes with the HP1 signal. This is the
      first description of altered nuclear distribution of HP1 proteins in the
      constitutional ICF syndrome. Our results show that satellite DNA hypomethylation
      does not prevent HP1 proteins from associating with heterochromatin. They suggest
      that, at G2 phase, HP1 proteins are involved in the heterochromatin condensation
      and may therefore remain concentrated at these sites until the condensation is
      complete. They also indicate that proteins from the NB could play a role in this
      process. Finally, satellite DNA length polymorphism could affect the efficiency
      of heterochromatin condensation and thus contribute to the variability of the ICF
      phenotype.

PMID- 15470360
TI  - Interaction between obesity-susceptibility loci in chromosome regions 2p25-p24
      and 13q13-q21.
AB  - One of the chief complexities of genetic influences on human obesity appears to
      be gene-gene interactions. Here, we employed model-free approaches to look for
      gene-gene interaction effects in human obesity using genome scan data from 260
      European American families. We found consistent evidence for statistical
      interaction between 2p25-p24 (18-38 cM) and 13q13-q21 (26-47 cM). For discrete
      traits, the positive correlations were significant at P<0.0001 (P</=0.0023 after
      correction for multiple tests) in both IBD-based and NPL-based analyses for
      BMI>/=40 kg/m(2). Other analytic approaches gave consistent, supportive results.
      For quantitative traits, interaction effects were significant for BMI (P=0.0012),
      percent fat (P=0.0265) and waist circumference (P=0.0023) in a Haseman-Elston
      regression model, and for BMI (P=0.0043) in variance component analysis. Our
      findings suggest that obesity-susceptibility loci in chromosome regions 2p25-p24
      and 13q13-21 may interact to influence extreme human obesity. The identification
      of gene-gene interactions may prove crucial to understanding the contributions of
      genes, which, by themselves, have relatively small effects on obesity
      susceptibility and resistance.

PMID- 15470361
TI  - New tools for preimplantation genetic diagnosis of Huntington's disease and their
      clinical applications.
AB  - Huntington's disease (HD) is a late-onset neurodegenerative disorder transmitted
      as an autosomal dominant trait. The causative mutation was characterised in 1993.
      For HD carriers willing to create a family, prenatal diagnosis (PND) or
      preimplantation genetic diagnosis (PGD) based on the mutation identification can
      be offered. For at-risk persons who do not want to undergo presymptomatic testing
      (PT), an exclusion test can be proposed. With such a test, only foetuses or
      embryos that inherit an allele from the unaffected grandparent are considered as
      unaffected. In cases of PND, if the foetus has one allele of the affected
      grandparent, termination of pregnancy is proposed. In cases of PGD, only not at
      risk embryos are transferred. Since the beginning of our PGD activity, we have
      had 43 PGD referrals for HD, of which 24 were from patients who know their
      genetic status and 19 from patients who do not wish to perform PT. We have
      developed 12 multiplex fluorescent PCR protocols applied at the single-cell level
      for PGD, some of which target the CAG repeat while others use two different
      polymorphic microsatellites. We present here these different protocols and their
      clinical applications, as well as the characterisation and use of a new highly
      polymorphic intragenic marker. Between May 2001 and December 2003, 39 PGD cycles
      have been performed for 17 couples, 11 of whom had a known genetic status and six
      who did not wish to perform PT, resulting in four pregnancies.

PMID- 15470362
TI  - A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD
      syndrome and Noonan-like/multiple giant cell lesion syndrome.
AB  - Noonan (NS) and multiple lentigines/LEOPARD syndromes (LS) have proved to be
      associated with distinct PTPN11 mutations. Noonan-like/multiple giant cell lesion
      syndrome (NLS) is a rare disease, characterised by short stature, facial
      dysmorphisms, congenital heart defect (CHD) and central giant cell lesions.
      PTPN11 gene mutations have been reported in a single NLS family and two sporadic
      patients. Here we report a patient with a complex phenotype progressing
      throughout the years from NS at birth towards LS and NLS. PTPN11 gene analysis
      disclosed a novel missense mutation (Ala461Thr) in exon 12, affecting the
      consensus sequence of the SHP2-active site. This observation joins together NS
      and LS to NLS into a unique genetic defect, broadening the clinical and molecular
      spectrum of PTPN11-related disorders.

PMID- 15470363
TI  - New insights on the evolution of the SMN1 and SMN2 region: simulation and meta
      analysis for allele and haplotype frequency calculations.
AB  - Most spinal muscular atrophy patients lack both copies of SMN1. Loss of SMN1 ('0
      copy alleles') can occur by gene deletion or SMN1-to-SMN2 gene conversion.
      Despite worldwide efforts to map the segmental duplications within the SMN
      region, most assemblies do not correctly delineate these genes. A near
      pericentromeric location provides impetus for the strong evidence that SMN1 and
      SMN2 arose from a primate-specific paralogous gene duplication. Here we meta
      analyzed our recent laboratory results together with available published data, in
      order to calculate new mutation rates and allele/haplotype frequencies in this
      recalcitrant and highly unstable region of the human genome. Based on our tested
      assumption of compliance with Hardy-Weinberg equilibrium, we conclude that the
      SMN1 allele frequencies are: '0-copy disease alleles,' 0.013; '1-copy normal
      alleles,' 0.95; '2-copy normal alleles (ie, two copies of SMN1 on one
      chromosome),' 0.038; and '1(D) disease alleles (SMN1 with a small intragenic
      mutation),' 0.00024. The SMN1 haplotype ['(SMN1 copy number)-(SMN2 copy number)']
      frequencies are: '0-0,' 0.00048; '0-1,' 0.0086; '0-2,' 0.0042; '1-0,' 0.27; '1
      1,' 0.66; '1-2,' 0.015; '2-0,' 0.027; and '2-1,' 0.012. Paternal and maternal de
      novo mutation rates are 2.1 x 10(-4) and 4.2 x 10(-5), respectively. Our data
      provide the basis for the most accurate genetic risk calculations, as well as new
      insights on the evolution of the SMN region, with evidence that nucleotide
      position 840 (where a transition 840C>T functionally distinguishes SMN2 from
      SMN1) constitutes a mutation hotspot. Our data also suggest selection of the 1-1
      haplotype and the presence of rare chromosomes with three copies of SMN1.

PMID- 15470364
TI  - Mutation analysis in the fibroblast growth factor 14 gene: frameshift mutation
      and polymorphisms in patients with inherited ataxias.
AB  - The spinocerebellar ataxias (SCAs) with autosomal dominant inheritance are a
      group of neurodegenerative disorders with overlapping as well as highly variable
      phenotypes. Genetically, at least 25 different loci have been identified. Seven
      SCAs are caused by CAG trinucleotide repeat expansions, for 13 the chromosomal
      localization is known solely. Recently, a missense mutation in the fibroblast
      growth factor 14 gene (FGF14) has been reported in a Dutch family with a new
      dominantly inherited form of SCA. To evaluate the frequency of mutations in the
      FGF14 gene, we performed molecular genetic analyses for the five exons in 208
      nonrelated familial ataxia cases and 208 control samples. In one patient, we
      detected a novel single base pair deletion in exon 4 (c.487delA) creating a
      frameshift mutation. In addition, we found DNA polymorphisms in exon 1a, 4, and
      5, an amino-acid exchange at position 124, as well as a single-nucleotide
      polymorphism in the 3'-untranslated region of exon 5.

PMID- 15470365
TI  - Familial pericentric inversion of chromosome 18: behavioral abnormalities in
      patients heterozygous for either the dup(18p)/del(18q) or dup(18q)/del(18p)
      recombinant chromosome.
AB  - We describe a family in which the largest hitherto reported pericentric inversion
      of chromosome 18, inv(18)(p11.22q23), segregates. Individuals heterozygous for
      the nonrecombinant inversion were unaffected. However, those heterozygous for
      either the dup(18p)/del(18q) or dup(18q) /del(18p) recombinant exhibited mild
      learning difficulty, personality disorders and deficient social behavior in the
      absence of mental retardation. Of the three family members tested, the behavioral
      abnormalities were more prominent in the two individuals with the
      dup(18p)/del(18q) recombinant than in the one with the dup(18q)/del(18p)
      recombinant. Genetic counseling issues for this family, in particular for the
      affected, include the enhanced probability of reduced fertility as well as the
      recurrence risk of the parental inversion equaling 1/2 in surviving offspring.
      This observation kindles the interest in determining the frequency of
      subtelomeric rearrangements in individuals with learning difficulty and
      deficiency in social interaction, phenotypic features often considered to be of
      multifactorial causation.

PMID- 15470366
TI  - A second locus mapping to 2q35-36 for familial pseudohyperkalaemia.
AB  - Familial pseudohyperkalaemia (FP) is a symptomless, dominantly inherited red cell
      trait, which shows a 'passive leak' of K+ cations into the plasma upon storage of
      blood at room temperature (or below). There are no haematological abnormalities.
      The loss of K+ is due to a change in the temperature dependence of the leak. The
      Scottish case initially described, FP Edinburgh, maps to 16q23-qter. Here we
      studied a large kindred of Flemish descent with FP, termed FP Lille, which was
      phenotypically identical to the Edinburgh FP. In FP Lille, however, the
      responsible locus mapped to 2q35-36, with a Lod score of 8.46 for marker D2S1338.
      We infer that FP Edinburgh and FP Lille, although they are phenocopies of one
      another, stem from two distinct loci, FP1 (16q23-qter) and FP2 (2q35-36),
      respectively. This duality hints at the possibility that the protein mediating
      the leak might be a heterodimer. No mutation was found in three plausibly
      candidate genes: the KCNE4 gene, the TUBA1 gene and a predicted gene located in
      genomic contig NT_005403.

PMID- 15470367
TI  - Association of the mitochondrial DNA haplogroup J with longevity is population
      specific.
AB  - Evidences are accumulating on the effects of the variability of mitochondrial DNA
      (mtDNA) on many complex traits. In particular, mtDNA haplogroup J has been
      reported to increase the individual chance to attain longevity in northern
      Italians, Northern Irish and Finns. However, since the genetic contribution to
      longevity may be population specific, we wanted to verify if haplogroup J does
      affect longevity also in a southern European population having a different
      genetic and environmental history. We analysed a population sample (883 subjects,
      371 males and 521 females; age range 18-108 years) from southern Italy for the
      presence of haplogroup J. No frequency increase of this mtDNA haplogroup was
      found in the older cohorts, suggesting that, in this population, haplogroup J
      does not play a significant role in longevity. This finding shows that, as for
      other genetic factors, the association of mtDNA inherited variability with
      longevity is population specific.

PMID- 15470368
TI  - Overdispersion of allele frequency differences between populations: implications
      for meta-analyses of genotypic disease associations.
AB  - Methods correcting case-control studies of genetic polymorphisms for unmeasured
      genetic population substructure by modelling the variation at a number of variant
      loci provide no standard and easily implemented approach to meta-analysis, which
      is a key to understanding the effects of minor genotypic risks on complex
      diseases. A correction of the odds ratio estimate and its confidence interval is
      shown to be easy to implement using a mixed effects logistic regression. The
      method is shown to substantially reduce bias and to give accurate coverage even
      when there is substantial overdispersion of allele frequency differences between
      populations. Major sequence classes of single-nucleotide polymorphism (SNP) are
      likely to act as valid controls for each other, since CpG SNPs did not differ in
      the extent of population structure from other SNPs. Agreement among investigators
      and journals to provide these straightforward statistics in publications of
      polymorphism studies will enhance the ability of future investigators to perform
      meta-analyses of weak genetic effects across accumulated studies that allow for
      population structure.

PMID- 15470370
TI  - Phenotypic variability in Angelman syndrome: comparison among different deletion
      classes and between deletion and UPD subjects.
AB  - Angelman syndrome (AS) can result from either a 15q11-q13 deletion (del),
      paternal uniparental disomy (UPD), imprinting, or UBE3A mutations. Here, we
      describe the phenotypic and behavioral variability detected in 49 patients with
      different classes of deletions and nine patients with UPD. Diagnosis was made by
      methylation pattern analysis of exon 1 of the SNRPN-SNURF gene and by
      microsatellite profiling of loci within and outside the 15q11-q13 region. There
      were no major phenotypic differences between the two main classes (BP1-BP3; BP2
      BP3) of AS deletion patients, except for the absence of vocalization, more
      prevalent in patients with BP1-BP3 deletions, and for the age of sitting without
      support, which was lower in patients with BP2-BP3 deletions. Our data suggest
      that gene deletions (NIPA1, NIPA2, CYF1P1, GCP5) mapped to the region between
      breakpoints BP1 and BP2 may be involved in the severity of speech impairment,
      since all BP1-BP3 deletion patients showed complete absence of vocalization,
      while 38.1% of the BP2-BP3 deletion patients were able to pronounce syllabic
      sounds, with doubtful meaning. Compared to UPD patients, deletion patients
      presented a higher incidence of swallowing disorders (73.9% del x 22.2% UPD) and
      hypotonia (73.3% del x 28.57% UPD). In addition, children with UPD showed better
      physical growth, fewer or no seizures, a lower incidence of microcephaly, less
      ataxia and higher cognitive skills. As a consequence of their milder or less
      typical phenotype, AS may remain undiagnosed, leading to an overall
      underdiagnosis of the disease.

PMID- 15470369
TI  - Family-based association study of DYX1C1 variants in autism.
AB  - DYX1C1: was recently identified as a candidate gene for developmental dyslexia,
      which is characterized by an unexpected difficulty in learning to read and write
      despite adequate intelligence, motivation, and education. It will be important to
      clarify, whether the phenotype caused by DYX1C1 extends to other language-related
      or comorbid disorders. Impaired language development is one of the essential
      features in autism. Therefore, we analyzed the allelic distribution of the DYX1C1
      gene by family-based association method in 100 Finnish autism families. No
      evidence for association was observed with any intragenic marker or with
      haplotypes constructed from alleles of several adjacent markers. No evidence for
      deviated allelic diversity was either observed: the frequency of expected
      dyslexia risk haplotype was comparable to its frequency in Finnish controls. Thus
      it seems unlikely that DYX1C1 gene would be involved in the genetic etiology of
      autism in Finnish patients.

PMID- 15470371
TI  - Situs ambiguus in a female fetus with balanced (X;21) translocation--evidence for
      functional nullisomy of the ZIC3 gene?
AB  - The human ZIC3 gene has been mapped to Xq26.2, the visceral heterotaxy locus
      HTX1, and has been shown to be mutated in X-linked situs ambiguus and/or complex
      heart defects. We report on a female fetus with situs ambiguus, asplenia and
      corrected transposition of the great arteries, displaying a (X;21) translocation.
      The balanced state of the t(X;21)(q26;p13) was verified by FISH on metaphase
      chromosomes of the fetus using DOP-PCR products of the microdissected der(21) and
      Xq-subtelomere specific sequences, and by PRINS with beta-satellite specific
      sequences. Examination with polymorphic markers flanking ZIC3 on DOP-PCR products
      of the microdissected der(21) chromosome evidenced that the complete copy of the
      ZIC3 gene was translocated to chromosome 21. Mutations in the fetal and parental
      ZIC3 genes were excluded by sequencing. Paternal origin of the der(X) and der(21)
      chromosomes was confirmed by use of polymorphic microsatellite markers from
      chromosome 21 and from the chromosomal region Xq26, respectively. X chromosome
      inactivation analysis using a PCR of a polymorphic (CAG)(n) repeat in the first
      exon of the androgen receptor gene showed a completely skewed X inactivation
      pattern with the paternal X as the active X chromosome, thus excluding functional
      disomy of distal Xq. A positional effect caused by the balanced (X;21)
      translocation may be responsible for functional nullisomy of ZIC3 and thus
      explain the situs and cardiac abnormalities in the fetus.

PMID- 15470372
TI  - Chronic stress decreases the number of parvalbumin-immunoreactive interneurons in
      the hippocampus: prevention by treatment with a substance P receptor (NK1)
      antagonist.
AB  - Previous studies have demonstrated that stress may affect the hippocampal
      GABAergic system. Here, we examined whether long-term psychosocial stress
      influenced the number of parvalbumin-containing GABAergic cells, known to provide
      the most powerful inhibitory input to the perisomatic region of principal cells.
      Adult male tree shrews were submitted to 5 weeks of stress, after which
      immunocytochemical and quantitative stereological techniques were used to
      estimate the total number of hippocampal parvalbumin-immunoreactive (PV-IR)
      neurons. Stress significantly decreased the number of PV-IR cells in the dentate
      gyrus (DG) (-33%), CA2 (-28%), and CA3 (-29%), whereas the CA1 was not affected.
      Additionally, we examined whether antidepressant treatment offered protection
      from this stress-induced effect. We administered fluoxetine (15 mg/kg per day)
      and SLV-323 (20 mg/kg per day), a novel neurokinin 1 receptor (NK1R) antagonist,
      because the NK1R has been proposed as a possible target for novel antidepressant
      therapies. Animals were subjected to a 7-day period of psychosocial stress before
      the onset of daily oral administration of the drugs, with stress continued
      throughout the 28-day treatment period. NK1R antagonist administration completely
      prevented the stress-induced reduction of the number of PV-IR interneurons,
      whereas fluoxetine attenuated this decrement in the DG, without affecting the CA2
      and CA3. The effect of stress on interneuron numbers may reflect real cell loss;
      alternatively, parvalbumin concentration is diminished in the neurons, which
      might indicate a compensatory attempt. In either case, antidepressant treatment
      offered protection from the effect of stress and appears to modulate the
      hippocampal GABAergic system. Furthermore, the NK1R antagonist SLV-323 showed
      neurobiological efficacy similar to that of fluoxetine.

PMID- 15470373
TI  - Effect of a single dose of levodopa on sexual response in men and women.
AB  - From animal research, there is ample evidence for a facilitating effect of
      dopamine on sexual behavior. In humans, little experimental research has been
      conducted on the inter-relation between dopamine and sexual response, even less
      so in women than in men. We investigated the effect of levodopa (100 mg) on
      sexual response in men and women following a double-blind, placebo-controlled
      crossover design. Genital and subjective sexual responses were measured as well
      as somatic motor system activity by means of Achilles tendon (T) reflex
      modulation. Genital and subjective sexual arousal were not affected by levodopa.
      However, the drug increased T reflex magnitude in response to sexual stimulation
      in men, but not in women. These results support the view that dopamine is
      involved in the energetic aspects of appetitive sexual behavior in men. The
      observed gender difference in the effect of levodopa is discussed in the
      perspective of possible dopamine-steroid interaction.

PMID- 15470374
TI  - The complexities of individual financial conflicts of interest.
AB  - Academic health centers (AHCs) are unique resources that are critical for the
      advancement of science and the training of health care providers, scientists, and
      educators. AHCs depend on public trust. Certain financial relationships between
      medical school faculty and industry create situations that have the potential to
      be deleterious to AHCs. Yet, the translation of clinically relevant, scientific
      advances to products that directly impact patients' lives benefits from
      entrepreneurial activities, and such activities necessitate interactions between
      academia and industry. Society has a vested interest in protecting human research
      participants, maintaining objectivity in scientific research, and encouraging
      creative research with clinical applications. Conflicts of interest (COI)
      committees have been created by AHCs to evaluate faculty financial COI and to
      develop strategies to eliminate, reduce, or manage such conflicts. Issues
      involving financial COI are relevant to psychiatry. These issues are reviewed
      from the perspective of regulatory oversight provided by a medical school's COI
      committee.

PMID- 15470375
TI  - Ronin, PhD.

PMID- 15470376
TI  - Challenges to informed consent.

PMID- 15470377
TI  - Accelerating drug discovery.

PMID- 15470378
TI  - Genomics and drugs. An interview conducted by Holger Breithaupt and Caroline
      Hadley.

PMID- 15470379
TI  - Fighting malaria at the crossroads.

PMID- 15470380
TI  - Room of its own.

PMID- 15470382
TI  - Of yeast and men. The evolution of PtdIns(3,4,5)P(3) synthesis.

PMID- 15470383
TI  - Multi-tasking by the p75 neurotrophin receptor: sortilin things out?
AB  - Signalling by the p75 neurotrophin receptor has been implicated in diverse
      neuronal responses, including increased differentiation or survival, inhibition
      of regeneration, and initiation of apoptotic cell death. These numerous roles are
      matched by, but are not yet correlated with, a multiplicity of extracellular
      ligands and intracellular interactors. Membrane proteins such as sortilin, a
      member of the Vps10p family of sorting receptors, and the
      glycosylphosphatidylinositol-linked Nogo receptor (NgR) and the associated
      adaptor lingo 1 have recently been added to the list of p75-interacting
      modulators. Other studies have described intramembranal cleavage of p75 and the
      potential nuclear targeting of cleavage fragments or of the complete receptor
      after it has been internalized into a putative signalling endosome. These
      findings suggest that some of the diversity in p75 activities might be due to
      differential subcellular localization and transport of p75 receptor complexes. We
      therefore argue that cell-biology-driven approaches are now required to make
      sense of p75 signalling.

PMID- 15470384
TI  - Duchenne muscular dystrophy and dystrophin: pathogenesis and opportunities for
      treatment.

PMID- 15470385
TI  - Bioturbators enhance ecosystem function through complex biogeochemical
      interactions.
AB  - Predicting the consequences of species loss is critically important, given
      present threats to biological diversity such as habitat destruction,
      overharvesting and climate change. Several empirical studies have reported
      decreased ecosystem performance (for example, primary productivity) coincident
      with decreased biodiversity, although the relative influence of biotic effects
      and confounding abiotic factors has been vigorously debated. Whereas several
      investigations focused on single trophic levels (for example, grassland plants),
      studies of whole systems have revealed multiple layers of feedbacks, hidden
      drivers and emergent properties, making the consequences of species loss more
      difficult to predict. Here we report functionally important organisms and
      considerable biocomplexity in a sedimentary seafloor habitat, one of Earth's most
      widespread ecosystems. Experimental field measurements demonstrate how the
      abundance of spatangoid urchins--infaunal (in seafloor sediment) grazers/deposit
      feeders--is positively related to primary production, as their activities change
      nutrient fluxes and improve conditions for production by microphytobenthos
      (sedimentatry microbes and unicellular algae). Declines of spatangoid urchins
      after trawling are well documented, and our research linking these bioturbators
      to important benthic-pelagic fluxes highlights potential ramifications for
      productivity in coastal oceans.

PMID- 15470386
TI  - Futures of artificial life.

PMID- 15470387
TI  - Kyoto challenge has just begun.

PMID- 15470388
TI  - US universities up in arms over licence plans for foreign staff.

PMID- 15470391
TI  - Colourful work on quarks scoops triple crown.

PMID- 15470392
TI  - Tardy earthquake excites California geophysicists.

PMID- 15470389
TI  - Science of smell wins medicine Nobel.

PMID- 15470393
TI  - Subtler tests urged for supercomputers.

PMID- 15470394
TI  - Britain warms to European space exploration plan.

PMID- 15470395
TI  - Blair to seek consensus on safe greenhouse-gas levels.

PMID- 15470397
TI  - Iraqi military research: rocket man.

PMID- 15470398
TI  - Semiconductor industry: chipping in.

PMID- 15470399
TI  - Synthetic biology: starting from scratch.

PMID- 15470400
TI  - Scientists and teachers should ignore politics.

PMID- 15470401
TI  - No mistake in Berkeley's biotechnology deal.

PMID- 15470402
TI  - Brazil needs action rather than words.

PMID- 15470407
TI  - The long and the short of it...

PMID- 15470408
TI  - Developmental biology: holding it together in the eye.

PMID- 15470409
TI  - Astromineralogy: dust in another solar system.

PMID- 15470410
TI  - Molecular biology: no exception to reversibility.

PMID- 15470413
TI  - Materials physics: doping control for nanotubes.

PMID- 15470412
TI  - Palaeontology: ecology of ice-age extinctions.

PMID- 15470414
TI  - Cell biology: light on pits.

PMID- 15470416
TI  - Chicken genomics: feather-pecking and victim pigmentation.
AB  - Feather-pecking in domestic birds is associated with cannibalism and severe
      welfare problems. It is a dramatic example of a spiteful behaviour in which the
      victim's fitness is reduced for no immediate direct benefit to the perpetrator
      and its evolution is unexplained. Here we show that the plumage pigmentation of a
      chicken may predispose it to become a victim: birds suffer more drastic feather
      pecking when the colour of their plumage is due to the expression of a wild
      recessive allele at PMEL17, a gene that controls plumage melanization, and when
      these birds are relatively common in a flock. These findings, obtained using an
      intercross between a domestic fowl and its wild ancestor, have implications for
      the welfare of domestic species and offer insight into the genetic changes
      associated with the evolution of feather-pecking during the early stages of
      domestication.

PMID- 15470417
TI  - Pair bonds: arrival synchrony in migratory birds.
AB  - Synchronous arrival of pairs of migratory birds at their breeding grounds is
      important for maintaining pair bonds and is achieved by pairs that remain
      together all year round. Here we show that arrival is also synchronized in paired
      individuals of a migratory shorebird, the black-tailed godwit (Limosa limosa
      islandica), even though they winter hundreds of kilometres apart and do not
      migrate together. The mechanisms required to achieve this synchrony and prevent
      'divorce' illustrate the complexity of migratory systems.

PMID- 15470418
TI  - Surface mechanics mediate pattern formation in the developing retina.
AB  - Pattern formation of biological structures involves organizing different types of
      cells into a spatial configuration. In this study, we investigate the physical
      basis of biological patterning of the Drosophila retina in vivo. We demonstrate
      that E- and N-cadherins mediate apical adhesion between retina epithelial cells.
      Differential expression of N-cadherin within a sub-group of retinal cells (cone
      cells) causes them to form an overall shape that minimizes their surface contact
      with surrounding cells. The cells within this group, in both normal and
      experimentally manipulated conditions, pack together in the same way as soap
      bubbles do. The shaping of the cone cell group and packing of its components
      precisely imitate the physical tendency for surfaces to be minimized. Thus,
      simple patterned expression of N-cadherin results in a complex spatial pattern of
      cells owing to cellular surface mechanics.

PMID- 15470419
TI  - Direct integration of Hox and segmentation gene inputs during Drosophila
      development.
AB  - During Drosophila embryogenesis, segments, each with an anterior and posterior
      compartment, are generated by the segmentation genes while the Hox genes provide
      each segment with a unique identity. These two processes have been thought to
      occur independently. Here we show that abdominal Hox proteins work directly with
      two different segmentation proteins, Sloppy paired and Engrailed, to repress the
      Hox target gene Distalless in anterior and posterior compartments, respectively.
      These results suggest that segmentation proteins can function as Hox cofactors
      and reveal a previously unanticipated use of compartments for gene regulation by
      Hox proteins. Our results suggest that these two classes of proteins may
      collaborate to directly control gene expression at many downstream target genes.

PMID- 15470420
TI  - An early extrasolar planetary system revealed by planetesimal belts in beta
      Pictoris.
AB  - beta Pictoris (beta Pic) is a main-sequence star with an edge-on dust disk that
      might represent a state of the early Solar System. The dust does not seem to be a
      remnant from the original protoplanetary disk, but rather is thought to have been
      generated from large bodies like planetesimals and/or comets. The history and
      composition of the parent bodies can therefore be revealed by determining the
      spatial distribution, grain size, composition and crystallinity of the dust
      through high-resolution mid-infrared observations. Here we report that the sub
      micrometre amorphous silicate grains around beta Pic have peaks in their
      distribution around 6, 16 and 30 au (1 au is the Sun-Earth distance), whereas the
      crystalline and micrometre-sized amorphous silicate grains are concentrated in
      the disk centre. As sub-micrometre grains are blown quickly out from the system
      by radiation pressure from the central star, the peaks indicate the locations of
      ongoing dust replenishment, which originates from ring-like distributions of
      planetesimals or 'planetesimal belts'.

PMID- 15470421
TI  - Magnesium sulphate salts and the history of water on Mars.
AB  - Recent reports of approximately 30 wt% of sulphate within saline sediments on
      Mars--probably occurring in hydrated form--suggest a role for sulphates in
      accounting for equatorial H2O observed in a global survey by the Odyssey
      spacecraft. Among salt hydrates likely to be present, those of the MgSO4*nH2O
      series have many hydration states. Here we report the exposure of several of
      these phases to varied temperature, pressure and humidity to constrain their
      possible H2O contents under martian surface conditions. We found that crystalline
      structure and H2O content are dependent on temperature-pressure history, that an
      amorphous hydrated phase with slow dehydration kinetics forms at <1% relative
      humidity, and that equilibrium calculations may not reflect the true H2O-bearing
      potential of martian soils. Mg sulphate salts can retain sufficient H2O to
      explain a portion of the Odyssey observations. Because phases in the MgSO4*nH2O
      system are sensitive to temperature and humidity, they can reveal much about the
      history of water on Mars. However, their ease of transformation implies that salt
      hydrates collected on Mars will not be returned to Earth unmodified, and that
      accurate in situ analysis is imperative.

PMID- 15470422
TI  - A superconductor to superfluid phase transition in liquid metallic hydrogen.
AB  - Although hydrogen is the simplest of atoms, it does not form the simplest of
      solids or liquids. Quantum effects in these phases are considerable (a
      consequence of the light proton mass) and they have a demonstrable and often
      puzzling influence on many physical properties, including spatial order. To date,
      the structure of dense hydrogen remains experimentally elusive. Recent studies of
      the melting curve of hydrogen indicate that at high (but experimentally
      accessible) pressures, compressed hydrogen will adopt a liquid state, even at low
      temperatures. In reaching this phase, hydrogen is also projected to pass through
      an insulator-to-metal transition. This raises the possibility of new state of
      matter: a near ground-state liquid metal, and its ordered states in the quantum
      domain. Ordered quantum fluids are traditionally categorized as superconductors
      or superfluids; these respective systems feature dissipationless electrical
      currents or mass flow. Here we report a topological analysis of the projected
      phase of liquid metallic hydrogen, finding that it may represent a new type of
      ordered quantum fluid. Specifically, we show that liquid metallic hydrogen cannot
      be categorized exclusively as a superconductor or superfluid. We predict that, in
      the presence of a magnetic field, liquid metallic hydrogen will exhibit several
      phase transitions to ordered states, ranging from superconductors to superfluids.

PMID- 15470423
TI  - A quantum fluid of metallic hydrogen suggested by first-principles calculations.
AB  - It is generally assumed that solid hydrogen will transform into a metallic alkali
      like crystal at sufficiently high pressure. However, some theoretical models have
      also suggested that compressed hydrogen may form an unusual two-component
      (protons and electrons) metallic fluid at low temperature, or possibly even a
      zero-temperature liquid ground state. The existence of these new states of matter
      is conditional on the presence of a maximum in the melting temperature versus
      pressure curve (the 'melt line'). Previous measurements of the hydrogen melt line
      up to pressures of 44 GPa have led to controversial conclusions regarding the
      existence of this maximum. Here we report ab initio calculations that establish
      the melt line up to 200 GPa. We predict that subtle changes in the intermolecular
      interactions lead to a decline of the melt line above 90 GPa. The implication is
      that as solid molecular hydrogen is compressed, it transforms into a low
      temperature quantum fluid before becoming a monatomic crystal. The emerging low
      temperature phase diagram of hydrogen and its isotopes bears analogies with the
      familiar phases of 3He and 4He (the only known zero-temperature liquids), but the
      long-range Coulomb interactions and the large component mass ratio present in
      hydrogen would result in dramatically different properties.

PMID- 15470424
TI  - Room-temperature ferromagnetic nanotubes controlled by electron or hole doping.
AB  - Nanotubes and nanowires with both elemental (carbon or silicon) and multi-element
      compositions (such as compound semiconductors or oxides), and exhibiting
      electronic properties ranging from metallic to semiconducting, are being
      extensively investigated for use in device structures designed to control
      electron charge. However, another important degree of freedom--electron spin, the
      control of which underlies the operation of 'spintronic' devices--has been much
      less explored. This is probably due to the relative paucity of nanometre-scale
      ferromagnetic building blocks (in which electron spins are naturally aligned)
      from which spin-polarized electrons can be injected. Here we describe nanotubes
      of vanadium oxide (VO(x)), formed by controllable self-assembly, that are
      ferromagnetic at room temperature. The as-formed nanotubes are transformed from
      spin-frustrated semiconductors to ferromagnets by doping with either electrons or
      holes, potentially offering a route to spin control in nanotube-based
      heterostructures.

PMID- 15470425
TI  - Biogenically driven organic contribution to marine aerosol.
AB  - Marine aerosol contributes significantly to the global aerosol load and
      consequently has an important impact on both the Earth's albedo and climate. So
      far, much of the focus on marine aerosol has centred on the production of aerosol
      from sea-salt and non-sea-salt sulphates. Recent field experiments, however, have
      shown that known aerosol production processes for inorganic species cannot
      account for the entire aerosol mass that occurs in submicrometre sizes. Several
      experimental studies have pointed to the presence of significant concentrations
      of organic matter in marine aerosol. There is some information available about
      the composition of organic matter, but the contribution of organic matter to
      marine aerosol, as a function of aerosol size, as well as its characterization as
      hydrophilic or hydrophobic, has been lacking. Here we measure the physical and
      chemical characteristics of submicrometre marine aerosol over the North Atlantic
      Ocean during plankton blooms progressing from spring through to autumn. We find
      that during bloom periods, the organic fraction dominates and contributes 63% to
      the submicrometre aerosol mass (about 45% is water-insoluble and about 18% water
      soluble). In winter, when biological activity is at its lowest, the organic
      fraction decreases to 15%. Our model simulations indicate that organic matter can
      enhance the cloud droplet concentration by 15% to more than 100% and is therefore
      an important component of the aerosol-cloud-climate feedback system involving
      marine biota.

PMID- 15470426
TI  - Basal tyrannosauroids from China and evidence for protofeathers in
      tyrannosauroids.
AB  - Tyrannosauroids are one of the last and the most successful large-bodied
      predatory dinosaur groups, but their early history remains poorly understood.
      Here we report a new basal tyrannosauroid from the Early Cretaceous Yixian
      Formation of western Liaoning, China, which is small and gracile and has
      relatively long arms with three-fingered hands. The new taxon is the earliest
      known unquestionable tyrannosauroid found so far. It shows a mosaic of
      characters, including a derived cranial structure resembling that of derived
      tyrannosauroids and a primitive postcranial skeleton similar to basal
      coelurosaurians. One of the specimens also preserves a filamentous integumentary
      covering similar to that of other coelurosaurian theropods from western Liaoning.
      This provides the first direct fossil evidence that tyrannosauroids had
      protofeathers.

PMID- 15470427
TI  - Pleistocene to Holocene extinction dynamics in giant deer and woolly mammoth.
AB  - The extinction of the many well-known large mammals (megafauna) of the Late
      Pleistocene epoch has usually been attributed to 'overkill' by human hunters,
      climatic/vegetational changes or to a combination of both. An accurate knowledge
      of the geography and chronology of these extinctions is crucial for testing these
      hypotheses. Previous assumptions that the megafauna of northern Eurasia had
      disappeared by the Pleistocene/Holocene transition were first challenged a decade
      ago by the discovery that the latest woolly mammoths on Wrangel Island,
      northeastern Siberia, were contemporaneous with ancient Egyptian civilization.
      Here we show that another spectacular megafaunal species, the giant deer or
      'Irish elk', survived to around 6,900 radiocarbon yr bp (about 7,700 yr ago) in
      western Siberia-more than three millennia later than its previously accepted
      terminal date-and therefore, that the reasons for its ultimate demise are to be
      sought in Holocene not Pleistocene events. Before their extinction, both giant
      deer and woolly mammoth underwent dramatic shifts in distribution, driven largely
      by climatic/vegetational changes. Their differing responses reflect major
      differences in ecology.

PMID- 15470428
TI  - Photosynthetic architecture differs in coastal and oceanic diatoms.
AB  - Diatoms are a key taxon of eukaryotic phytoplankton and a major contributor to
      global carbon fixation. They are ubiquitous in the marine ecosystem despite
      marked gradients in environmental properties, such as dissolved iron
      concentrations, between coastal and oceanic waters. Previous studies have shown
      that offshore species of diatoms and other eukaryotic algae have evolved lower
      iron requirements to subsist in iron-poor oceanic waters, but the biochemical
      mechanisms responsible for their decreased iron demand are unknown. Here we show,
      using laboratory-cultured model species, a fundamental difference between a
      coastal and an oceanic diatom in their photosynthetic architecture. Specifically,
      the oceanic diatom had up to fivefold lower photosystem I and up to sevenfold
      lower cytochrome b6f complex concentrations than a coastal diatom. These changes
      to the photosynthetic apparatus markedly decrease the cellular iron requirements
      of the oceanic diatom but not its photosynthetic rates. However, oceanic diatoms
      might have also sacrificed their ability to acclimate to rapid fluctuations in
      light intensity--a characteristic of dynamic and turbid coastal waters. We
      suggest that diatoms, and probably other eukaryotic algal taxa, exploited this
      difference in the underwater light climate between oceanic and coastal waters,
      enabling them to decrease their iron requirements without compromising
      photosynthetic capacity. This adaptation probably facilitated the colonization of
      the open ocean by diatoms, and contributes to their persistence in this iron
      impoverished environment.

PMID- 15470429
TI  - Pleiotropy as a mechanism to stabilize cooperation.
AB  - Most genes affect many traits. This phenomenon, known as pleiotropy, is a major
      constraint on evolution because adaptive change in one trait may be prevented
      because it would compromise other traits affected by the same genes. Here we show
      that pleiotropy can have an unexpected effect and benefit one of the most
      enigmatic of adaptations--cooperation. A spectacular act of cooperation occurs in
      the social amoeba Dictyostelium discoideum, in which some cells die to form a
      stalk that holds the other cells aloft as reproductive spores. We have identified
      a gene, dimA, in D. discoideum that has two contrasting effects. It is required
      to receive the signalling molecule DIF-1 that causes differentiation into
      prestalk cells. Ignoring DIF-1 and not becoming prestalk should allow cells to
      cheat by avoiding the stalk. However, we find that in aggregations containing the
      wild-type cells, lack of the dimA gene results in exclusion from spores. This
      pleiotropic linkage of stalk and spore formation limits the potential for
      cheating in D. discoideum because defecting on prestalk cell production results
      in an even greater reduction in spores. We propose that the evolution of
      pleiotropic links between cheating and personal costs can stabilize cooperative
      adaptations.

PMID- 15470430
TI  - Migratory neural crest-like cells form body pigmentation in a urochordate embryo.
AB  - The neural crest, a source of many different cell types in vertebrate embryos,
      has not been identified in other chordates. Current opinion therefore holds that
      neural crest cells were a vertebrate innovation. Here we describe a migratory
      cell population resembling neural crest cells in the ascidian urochordate
      Ecteinascidia turbinata. Labelling of embryos and larvae with the vital
      lipophilic dye DiI enabled us to detect cells that emerge from the neural tube,
      migrate into the body wall and siphon primordia, and subsequently differentiate
      as pigment cells. These cells express HNK-1 antigen and Zic gene markers of
      vertebrate neural crest cells. The results suggest that migratory cells with some
      of the features of neural crest cells are present in the urochordates. Thus, we
      propose a hypothesis for neural crest evolution beginning with the release of
      migratory cells from the CNS to produce body pigmentation in the common ancestor
      of the urochordates and vertebrates. These cells may have gained additional
      functions or were joined by other cell types to generate the variety of
      derivatives typical of the vertebrate neural crest.

PMID- 15470431
TI  - Role for a cortical input to hippocampal area CA1 in the consolidation of a long
      term memory.
AB  - A dialogue between the hippocampus and the neocortex is thought to underlie the
      formation, consolidation and retrieval of episodic memories, although the nature
      of this cortico-hippocampal communication is poorly understood. Using selective
      electrolytic lesions in rats, here we examined the role of the direct entorhinal
      projection (temporoammonic, TA) to the hippocampal area CA1 in short-term (24
      hours) and long-term (four weeks) spatial memory in the Morris water maze. When
      short-term memory was examined, both sham- and TA-lesioned animals showed a
      significant preference for the target quadrant. When re-tested four weeks later,
      sham-lesioned animals exhibited long-term memory; in contrast, the TA-lesioned
      animals no longer showed target quadrant preference. Many long-lasting memories
      require a process called consolidation, which involves the exchange of
      information between the cortex and hippocampus. The disruption of long-term
      memory by the TA lesion could reflect a requirement for TA input during either
      the acquisition or consolidation of long-term memory. To distinguish between
      these possibilities, we trained animals, verified their spatial memory 24 hours
      later, and then subjected trained animals to TA lesions. TA-lesioned animals
      still exhibited a deficit in long-term memory, indicating a disruption of
      consolidation. Animals in which the TA lesion was delayed by three weeks,
      however, showed a significant preference for the target quadrant, indicating that
      the memory had already been adequately consolidated at the time of the delayed
      lesion. These results indicate that, after learning, ongoing cortical input
      conveyed by the TA path is required to consolidate long-term spatial memory.

PMID- 15470433
TI  - The philanthropic principle.

PMID- 15470432
TI  - Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918
      pandemic virus.
AB  - The 'Spanish' influenza pandemic of 1918-19 was the most devastating outbreak of
      infectious disease in recorded history. At least 20 million people died from
      their illness, which was characterized by an unusually severe and rapid clinical
      course. The complete sequencing of several genes of the 1918 influenza virus has
      made it possible to study the functions of the proteins encoded by these genes in
      viruses generated by reverse genetics, a technique that permits the generation of
      infectious viruses entirely from cloned complementary DNA. Thus, to identify
      properties of the 1918 pandemic influenza A strain that might be related to its
      extraordinary virulence, viruses were produced containing the viral
      haemagglutinin (HA) and neuraminidase (NA) genes of the 1918 strain. The HA of
      this strain supports the pathogenicity of a mouse-adapted virus in this animal.
      Here we demonstrate that the HA of the 1918 virus confers enhanced pathogenicity
      in mice to recent human viruses that are otherwise non-pathogenic in this host.
      Moreover, these highly virulent recombinant viruses expressing the 1918 viral HA
      could infect the entire lung and induce high levels of macrophage-derived
      chemokines and cytokines, which resulted in infiltration of inflammatory cells
      and severe haemorrhage, hallmarks of the illness produced during the original
      pandemic.

PMID- 15470436
TI  - Nuts and bolts. Totally stumped?

PMID- 15470434
TI  - Centre stage in Missouri.

PMID- 15470438
TI  - End of the interlude?

PMID- 15470439
TI  - Electoral campaign delays resolution of biotech issues.

PMID- 15470440
TI  - Growing pains in AIDS drug development.

PMID- 15470441
TI  - Inhaled insulin products puff along.

PMID- 15470442
TI  - China moves to reform biotech policies.

PMID- 15470443
TI  - Genentech discloses safety concerns over Avastin.

PMID- 15470445
TI  - Profile: Fritjof Capra.

PMID- 15470446
TI  - Biotech patenting matures.

PMID- 15470447
TI  - A taste of the future.

PMID- 15470448
TI  - Putting Cartagena into practice.

PMID- 15470449
TI  - The need for international stem cell agreements.

PMID- 15470451
TI  - Data hoarding is harming proteomics.

PMID- 15470452
TI  - A partnership between biology and engineering.

PMID- 15470453
TI  - The impact of systems approaches on biological problems in drug discovery.

PMID- 15470454
TI  - Two-dimensional annotation of genomes.

PMID- 15470455
TI  - More than meets the eyes?

PMID- 15470456
TI  - Can complexity be commercialized?

PMID- 15470457
TI  - Towards quality assurance and harmonization of genetic testing services in the
      European Union.

PMID- 15470458
TI  - Embryonic stem cells pace the heart.

PMID- 15470459
TI  - Phasing in iodine for structure determination.

PMID- 15470460
TI  - A universal TANGO?

PMID- 15470461
TI  - Climbing the protein ladder.

PMID- 15470462
TI  - Engineering sweet targets for magic bullets.

PMID- 15470464
TI  - The evolution of molecular biology into systems biology.
AB  - Systems analysis has historically been performed in many areas of biology,
      including ecology, developmental biology and immunology. More recently, the
      genomics revolution has catapulted molecular biology into the realm of systems
      biology. In unicellular organisms and well-defined cell lines of higher
      organisms, systems approaches are making definitive strides toward scientific
      understanding and biotechnological applications. We argue here that two distinct
      lines of inquiry in molecular biology have converged to form contemporary systems
      biology.

PMID- 15470465
TI  - Systems biology in drug discovery.
AB  - The hope of the rapid translation of 'genes to drugs' has foundered on the
      reality that disease biology is complex, and that drug development must be driven
      by insights into biological responses. Systems biology aims to describe and to
      understand the operation of complex biological systems and ultimately to develop
      predictive models of human disease. Although meaningful molecular level models of
      human cell and tissue function are a distant goal, systems biology efforts are
      already influencing drug discovery. Large-scale gene, protein and metabolite
      measurements ('omics') dramatically accelerate hypothesis generation and testing
      in disease models. Computer simulations integrating knowledge of organ and system
      level responses help prioritize targets and design clinical trials. Automation of
      complex primary human cell-based assay systems designed to capture emergent
      properties can now integrate a broad range of disease-relevant human biology into
      the drug discovery process, informing target and compound validation, lead
      optimization, and clinical indication selection. These systems biology approaches
      promise to improve decision making in pharmaceutical development.

PMID- 15470466
TI  - Exploiting biological complexity for strain improvement through systems biology.
AB  - Cellular complexity makes it difficult to build a complete understanding of
      cellular function but also offers innumerable possibilities for modifying the
      cellular machinery to achieve a specific purpose. The exploitation of cellular
      complexity for strain improvement has been a challenging goal for applied
      biological research because it requires the coordinated understanding of multiple
      cellular processes. It is therefore pursued most efficiently in the framework of
      systems biology. Progress in strain improvement will depend not only on advances
      in technologies for high-throughput measurements but, more importantly, on the
      development of theoretical methods that increase the information content of these
      measurements and, as such, facilitate the elucidation of mechanisms and the
      identification of genetic targets for modification.

PMID- 15470467
TI  - The challenges of modeling mammalian biocomplexity.
AB  - Understanding the relationships between human genetic factors, the risks of
      developing major diseases and the molecular basis of drug efficacy and toxicity
      is a fundamental problem in modern biology. Predicting biological outcomes on the
      basis of genomic data is a major challenge because of the interactions of
      specific genetic profiles with numerous environmental factors that may
      conditionally influence disease risks in a nonlinear fashion. 'Global' systems
      biology attempts to integrate multivariate biological information to better
      understand the interaction of genes with the environment. The measurement and
      modeling of such diverse information sets is difficult at the analytical and
      bioinformatic modeling levels. Highly complex animals such as humans can be
      considered 'superorganisms' with an internal ecosystem of diverse symbiotic
      microbiota and parasites that have interactive metabolic processes. We now need
      novel approaches to measure and model metabolic compartments in interacting cell
      types and genomes that are connected by cometabolic processes in symbiotic
      mammalian systems.

PMID- 15470468
TI  - The level of disclosure necessary for patent protection of genetic innovations.

PMID- 15470472
TI  - What is a hidden Markov model?

PMID- 15470473
TI  - Ten thousand interactions for the molecular biologist.
AB  - Previous studies have suggested that nature is restricted to about 1,000 protein
      folds to perform a great diversity of functions. Here, we use protein interaction
      data from different sources and three-dimensional structures to suggest that the
      total number of interaction types is also limited, and estimate that most
      interactions in nature will conform to one of about 10,000 types. We currently
      know fewer than 2,000, and at the present rate of structure determination, it
      will be more than 20 years before we know a full representative set.

PMID- 15470474
TI  - Changing talent needs to realize biotech products.

PMID- 15470475
TI  - Interleukin-1beta polymorphisms in Colombian patients with autoimmune rheumatic
      diseases.
AB  - Interleukin-1 beta (IL-1beta) exerts a range of inflammatory and immunomodulatory
      activities that are important in host defense and autoimmune response. The IL
      1beta gene, located on chromosome 2 (2q13), is polymorphic. The influence of its
      polymorphism on 355 patients with autoimmune rheumatic diseases was examined. To
      this effect, 172 patients with rheumatoid arthritis (RA), 114 with systemic lupus
      erythematosus (SLE), and 69 with primary Sjogren's syndrome (pSS) were studied.
      The control group consisted of 392 matched healthy individuals. Genotyping of IL
      1beta single-nucleotide polymorphisms (SNPs) at positions -511 (C/T) and + 3953
      (C/T) was performed by the polymerase chain reaction-restriction fragment length
      polymorphism technique. In addition, levels of IL-1beta were measured by
      immunoassay in supernatants of lipopolysaccharide (LPS)-stimulated and
      nonstimulated peripheral blood monocytes (PBM) obtained from 19 homozygous
      individuals for the three most common IL-1beta likely haplotypes, all belonging
      to the control group. Allele + 3953T was protective for SLE (odds ratio (OR) =
      0.57, 95% confidence intervals (CI) = 0.34-0.88, P = 0.01) as was the haplotype 
      511C + 3953T (OR = 0.43, 95%CI = 0.25-0.74, pc = 0.006). The latter was
      associated with a lower LPS-stimulated-PBM IL-1beta secretion. Results suggest
      that IL-1beta polymorphism influences the susceptibility to acquire SLE in our
      population. The protective association might be explained by the observed
      inhibitory effect of IL-1beta + 3953T allele on the secretion of IL-1beta under
      inflammatory circumstances.

PMID- 15470476
TI  - Cytokine genetic adjuvant facilitates prophylactic intravascular DNA vaccine
      against acute and latent herpes simplex virus infection in mice.
AB  - Intravascular plasmid DNA (pDNA) vaccine encoding herpes simplex virus type 1
      (HSV-1) glycoprotein B (gB) effectively induces prophylactic immunity against
      lethal HSV-1 infection in mice. We investigated whether the vaccine potency is
      further improved by coadministration of cytokine genes together with a low dose
      of genetic vaccine. pDNA encoding IL-12, IL-15, IL-18 or IL-21 was capable of
      elevating survival rates of HSV-1-infected mice when coinjected with 1 microg of
      gB pDNA, while IL-10 gene delivery failed to affect the effectiveness of the
      genetic immunization. Although only 17% of mice survived acute HSV infection
      after the gB pDNA vaccination at a dose of 1 microg, all mice coadministered with
      1 microg each of gB and IL-12 pDNAs not only survived the acute infection but
      also escaped latent infection. In these animals, the neutralizing antibody
      against HSV-1 was abundantly produced, and CTL activity against the gB antigen
      was augmented. Coadministration of the gB and IL-12 genes also elevated the serum
      level of interferon-gamma. Adaptive transfer experiments indicated that soluble
      factors contributed to preventive immunity, while cell components alone were not
      capable of protecting mice from fatal viral infection. These results strongly
      suggest potential usefulness of Th1 cytokine genes as effective molecular
      adjuvants that facilitate specific humoral as well as cellular immune responses
      elicited by intravascular molecular vaccination.

PMID- 15470477
TI  - Electroporative transfection with KGF-1 DNA improves wound healing in a diabetic
      mouse model.
AB  - We recently demonstrated that electroporation enhances transfection in a mouse
      wound-healing model. Keratinocyte growth factor (KGF) is an inducer of epithelial
      cell proliferation and differentiation and has been shown to be under expressed
      in the wounds of diabetic individuals. We hypothesized that KGF delivered into an
      excisional wound via naked DNA injection with subsequent electroporation would be
      a novel and potentially effective method to enhance wound closure in a diabetic
      mouse model. ELISA assays confirmed production of KGF protein in cultured mouse
      cells and RT-PCR assays confirmed KGF mRNA in skin samples taken from mice. In
      all, 32 genetically diabetic mice were given two identical excisional wounds of
      their dorsum and split into two groups with one group receiving KGF DNA injection
      and electroporation with the other group receiving no treatment. Over 90% of
      wounds healed in the presence of KGF and electroporation versus 40% in the
      untreated group by day 12. Histological analysis of the wounds demonstrated that
      untreated wounds contained microulcers with thin or incomplete epithelium with
      unresolved inflammation as compared to treated wounds where intact and mature
      epithelium was observed. Taken together these findings suggest that a single
      injection of KGF DNA encoded on a plasmid coupled with electroporation improves
      and accelerates wound closure in a delayed wound-healing model.

PMID- 15470478
TI  - Gene knockdown with intrathecal siRNA of NMDA receptor NR2B subunit reduces
      formalin-induced nociception in the rat.
AB  - N-methyl-D-aspartate (NMDA) receptor activation, at the level of the spinal cord,
      has been shown to play an important role in the facilitation of nociception in
      several animal models. However, the use of NMDA antagonists as analgesics is
      limited by serious side effects due to nonselective effects among the NMDA
      receptor subtypes. Recent discoveries revealed that the transfection of small
      interfering RNAs (siRNAs) into animal cells resulted in the potent, long-lasting,
      post-transcriptional silencing of specific genes. Thus, we investigated the
      effect of intrathecal (i.t.) injection of siRNAs targeting NMDA-R2B receptor
      subunit protein (NR2B) receptors, a subunit of NMDA receptor, for the modulation
      of pain. The results indicate that the use of siRNA targeting the NR2B subunit
      not only decreased the expression of NR2B mRNA and its associated protein, as
      demonstrated by real-time PCR and Western blotting, but also abolished formalin
      induced pain behaviors in rat model. The peak effect occurred on day 3 for mRNA
      and day 7 for its protein, following i.t. injection of 5 microg of siRNA-NR2B.
      These data prove the feasibility of i.t. siRNAs in the investigation of
      functional gene expression in the context of whole animal behavior for the
      management of chronic pain.

PMID- 15470479
TI  - Nonviral monocyte chemoattractant protein-1 gene transfer improves arteriogenesis
      after femoral artery occlusion.
AB  - Local infusion of recombinant monocyte chemoattractant protein-1 (MCP-1) has been
      shown to enhance collateral artery formation in rabbit and pig hindlimb models.
      Owing to clinical disadvantages of protein infusion, a nonviral, liposome-based
      MCP-1 gene transfer was developed. Collateralization in a porcine hindlimb model
      served to provide a proof-of-principle for the functional benefit of MCP-1
      overexpression. Development of arterial conductance as a measure of functionally
      relevant collateralization was evaluated in occluded as well as untreated
      hindlimbs in each animal. At the time of occlusion, MCP-1 and control DNA/DC-30
      lipoplexes were transferred to femoral arteries of Goettingen minipigs (two
      therapeutic MCP-1 groups: 2 and 4 microg and one control group), using the
      Infiltrator local drug-delivery device. At 2 weeks following occlusion,
      collateralization was determined as changes in peripheral haemodynamic
      conductance, peripheral over aortic blood pressure ratio and angiographically
      visible morphology of the peripheral vessel tree. Nonviral MCP-1 gene transfer
      significantly improved peripheral conductance (control 11.69+/-2.78%, 2 microg
      23.81+/-2.81%, P<0.05 and 4 microg 23.36+/-3.1%, P<0.05; n=12 per group) as well
      as the ratio of peripheral over aortic blood pressure (control 0.64+/-0.03%, 2
      microg 0.75+/-0.02%, P<0.05 and 4 mug 0.75+/-0.02%, P<0.05; n=12 per group) when
      compared to the untreated controls 2 weeks after occlusion. Thus, it could be
      demonstrated for the first time that in situ overexpression of MCP-1 following
      local nonviral gene transfer is a potential approach to improve peripheral
      collateralization.

PMID- 15470480
TI  - HSV vector-mediated transduction and GDNF secretion from adipose cells.
AB  - The accessibility of adipose tissue and its ability to secrete various bioactive
      molecules suggest that adipose cells may be attractive targets for gene therapy
      applications. Here, we report the use of highly defective herpes simplex virus
      (HSV) vectors as suitable gene transfer agents for adipose cells in culture and
      fat tissue in animals. Using an in vitro model of human adipose differentiation,
      we first demonstrated that mature adipocytes and their precursor cells express
      the two principal HSV viral entry receptors HveA and HveC (nectin-1) and are
      efficiently transduced at a low multiplicity of infection by HSV-lacZ reporter
      gene and glial cell line-derived neurotrophic factor (GDNF) gene vectors.
      Extended expression of beta-galactosidase and secretion of GDNF occurred in
      transduced fat tissue explants from rabbits. In vivo gene transfer to rabbit
      subcutaneous adipose tissue resulted in local GDNF expression for at least 2
      months. These experiments establish the efficient transduction of adipose cells
      by HSV vectors and suggest that fat tissue may represent a useful site for HSV
      mediated gene delivery with potential for therapeutic applications.

PMID- 15470481
TI  - Transbronchial administration of adenoviral-mediated interleukin-10 gene to the
      donor improves function in a pig lung transplant model.
AB  - Interleukin-10 (IL-10) gene transfection of donor lungs prior to transplantation
      is an attractive strategy to reduce ischemia-reperfusion induced lung injury.
      However, experimental data with gene therapy in large animal models of lung
      transplantation are generally lacking. We have developed a simple clinically
      applicable technique for adenoviral-mediated gene delivery of human IL-10 to the
      lung of large animals that provides homogenous gene expression after 12-24 h of
      transfection. Using this technique of gene delivery, we have studied the dynamics
      of adenoviral gene delivery to the lung in the setting of lung transplantation.
      Although there is a persistent inflammatory response to the adenoviral vector, we
      achieved significant expression of human IL-10 in lung tissue before lung
      retrieval to obviate the deleterious impact of the adenoviral vector on the donor
      lung. The administration of adenoviral-mediated human IL-10 to the donor lung
      reduced ischemia-reperfusion injury and improved graft function after lung
      transplantation in this pig lung transplantation model. Transfection of
      adenoviral-mediated human IL-10 to the donor lung prevented the release of
      inflammatory cytokines such as IL-6 in lung tissue and plasma. We have
      demonstrated that IL-10 gene therapy has significant potential to prevent or
      treat the inflammatory response associated with ischemia-reperfusion injury in
      lung transplantation. In the future, IL-10 gene therapy could also be used for
      immunomodulation or tolerance induction.

PMID- 15470482
TI  - Polyethyleneimine grafted with pluronic P85 enhances Ku86 antisense delivery and
      the ionizing radiation treatment efficacy in vivo.
AB  - In an effort to improve the efficacy of antisense delivery, we evaluated
      polyethyleneimine (PEI, 2 kDa) alone or grafted with nonionic amphiphilic block
      copolymer Pluronic (P85) as a carrier for Ku86 antisense oligonucleotide (ASO)
      delivery. Ku86 is an abundant nuclear protein that plays an important role in
      nonhomologous DNA end joining and has implications in tumorigenesis and acquired
      drug resistance. Transfection of adherent and suspension cell lines with Ku86
      ASOs complexed with P85-g-PEI (2 kDa) conjugates was associated with a specific
      decrease in Ku86 mRNA levels (EC50<75 nM and EC50<250 nM, respectively, n=3).
      More importantly, no requirement for reduced serum conditions was necessary
      during transfection. In contrast, whereas Ku86 ASOs complexed with PEI (2 kDa)
      alone were effective in decreasing Ku86 mRNA levels in adherent cell lines
      (EC50<75 nM, n=3), the formulation did not produce any detectable decrease in
      Ku86 mRNA levels in suspension cell lines. Transfection of adherent cell lines
      with 500 nM Ku86 ASOs formulated with P85-g-PEI (2 kDa) was associated with a
      specific decrease (<10% remaining of control) in Ku86 protein expression and a
      two-fold increased cell death after treatment with ionizing radiation (IR). In
      athymic nude mice bearing subcutaneous human HT29 colon adenocarcinoma
      xenografts, Ku86 ASO-P85-g-PEI (2 kDa) administration (15 mg/kg, subcutaneously)
      with a Q1D x 7 treatment schedule, when combined with a single dose of IR (6 Gy),
      caused a significant inhibition of HT29 tumor growth compared with mismatch- and
      naked antisense-pretreated control groups (time from 200 to 1000 mm3, 126.9
      versus 84.18 and 87.76 days, P<0.005). A potentiation of the antitumor activity
      was observed in all mice treated with Ku86 ASO-P85-g-PEI (2 kDa) formulation;
      however, tumor growth inhibition was reversible upon treatment cessation. No
      morbidity/mortality or changes in histopathology were observed under this
      treatment regiment. Our results indicate that P85-g-PEI (2 kDa) conjugates may
      increase the efficacy of Ku86 ASO delivery in management of resistant
      malignancies, thus providing a rationale for their evaluation in cancer patients
      in combination with conventional anticancer therapies.

PMID- 15470483
TI  - A randomized trial on sodium reduction in two developing countries.
AB  - Hypertension remains the most common cardiovascular risk factor in developing
      countries, yet the majority of patients have no access to pharmacological
      therapy. Population-wide preventive strategies, such as salt restriction, are an
      attractive alternative, but experience in resource-poor settings is limited. To
      address this question, we conducted a randomized crossover study of salt
      restriction in adults living in Nigeria and Jamaica in order to estimate the mean
      blood pressure (BP) response. After a 4-week run-in period to determine
      willingness to adhere to a low-salt diet, 56 Jamaicans and 58 Nigerians completed
      an 8-week crossover study of low-salt and high-salt intake. Baseline BPs were in
      the normotensive range (systolic=125 mmHg in Jamaica, 114 mmHg in Nigeria).
      Baseline urinary sodium excretion was 86.8 and 125.6 mEq/day in Nigeria and
      Jamaica, respectively. The mean difference between urinary sodium excretion at
      baseline and at the end of the 3-week low-sodium phase was 33.6 mEq/day in
      Nigeria and 57.5 mEq/day in Jamaica. During the high-sodium phase, mean change in
      urinary sodium excretion from baseline to week 3 was 35.0 and 5.5 mEq/day in
      Nigeria and Jamaica, respectively. The mean change in systolic BP ('high' vs
      'low' sodium phase) was approximately 5 mmHg in both groups. This study suggests
      that the efficacy of sodium reduction in developing countries equals those noted
      in more affluent cultures. If promoted on a wide scale, sodium reduction could be
      used to treat persons with established hypertension, and more importantly, to
      prevent age-related increases in BP in poor communities.

PMID- 15470484
TI  - FcgammaRIIB expression in diffuse large B-cell lymphomas does not alter the
      response to CHOP+rituximab (R-CHOP).

PMID- 15470485
TI  - Prevention of venous thromboembolism with low molecular-weight heparin in
      patients with multiple myeloma treated with thalidomide and chemotherapy.

PMID- 15470486
TI  - Raf and VEGF: emerging therapeutic targets in Kaposi's sarcoma-associated
      herpesvirus infection and angiogenesis in hematopoietic and nonhematopoietic
      tumors.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with
      several cancers including Kaposi's sarcoma (KS), primary effusion lymphoma, and
      multicentric Castleman's disease. KSHV-mediated pathogenesis is dependent mainly
      on KSHV infection as well as on the microenvironment provided by the growth
      factors (GFs)/inflammatory cytokines (ICs). Recently, we determined that
      oncoprotein Raf enhances KSHV infection of target cells. Interestingly, Raf
      regulates the expression of a variety of GFs/ICs including those involved in
      angiogenesis such as vascular endothelial growth factor (VEGF). In this review,
      we discuss the effect of the Raf-GF/IC autocrine/paracrine loop on KSHV infection
      of both hematopoietic and nonhematopietic cells, and associated disease
      conditions.

PMID- 15470488
TI  - Gene expression profiling of minimal residual disease in acute myeloid leukaemia
      by novel multiplex-PCR-based method.
AB  - In acute myeloid leukaemia (AML), alterations in apoptotic pathways are crucial
      for treatment outcome, resulting either in refractoriness or in minimal residual
      disease (MRD). The apoptosis characteristics of MRD cells may differ from those
      at diagnosis and thereby determine the adequacy of further treatment. Such
      characteristics are largely unknown, since studies hereto are hampered by minimal
      cell availability. This study explores the applicability of the recently
      described RT-Multiplex Ligation-dependent Probe Amplification (RT-MLPA) for gene
      expression analysis of small amounts of RNA obtained from MRD cells.
      Reproducibility and dilution experiments showed that the relative expression of
      37 apoptosis-related genes starting with only 1000 cells could be measured with
      12% variation; for 100 cells, 31/37 genes could still be quantified, though
      expression variation increased. In practice 100-1000 leukemic cells can be
      obtained from bone marrow samples with clinically relevant MRD percentages of
      0.01-0.1. Procedures often necessary to obtain AML blasts, that is, FACS-sorting,
      freeze-thawing or combinations are possible, provided that selected viable
      nonapoptotic cells are used. Concluding, RT-MLPA allows accurate gene expression
      profiling of MRD cells. This method will help to gain insight into the processes
      of MRD emergence and persistence in AML, which may ultimately guide new
      therapeutic strategies in AML.

PMID- 15470487
TI  - Identification of natural killer cell receptor phenotypes associated with
      leukemia.
AB  - Natural killer (NK) cells play a key role in defense against tumor cells that
      have the capacity to downregulate human leukocyte antigen (HLA) class I
      expression. It has been reported that leukemic cells can have downregulated
      expression of HLA class I molecules. The polymorphic nature of NK cell receptor
      (NKR) genes generates diverse repertoires in the human population, which display
      specificity in the innate immune response. In the present study, 11 KIR and two
      CD94/NKG2 receptors were genotyped by PCR-SSP in 96 leukemic patients and 148
      healthy Caucasians. Here, we report a significant increased frequency of the more
      inhibitory AB killer cell immunoglobulin-like receptor (KIR) phenotype in
      leukemic patients compared to the controls (31.1% in healthy controls vs 51.0% in
      leukemic patients, Pc=0.002), which is related to the high prevalence of the
      inhibitory KIR2DL2 in this population (Pc=0.007). Moreover, two specific KIR
      phenotypes AB1 and AB9, including all inhibitory KIRs, were significantly
      associated with leukemic patients. Our study suggests that an important
      percentage of leukemic patients express a KIR phenotype in favor of escape from
      NK cell immunity.

PMID- 15470489
TI  - Grb7 expression and cellular migration in chronic lymphocytic leukemia: a
      comparative study of early and advanced stage disease.
AB  - Grb7, a noncatalytic intracellular adaptor protein involved in cell migration, is
      overexpressed in certain invasive and metastatic solid tumors. We found a highly
      significant difference in the level of expression of Grb7 between chronic
      lymphocytic leukemia (CLL) cells obtained from stage I and stage IV patients
      (P<0.001). Using semiquantitative RT-PCR, we detected high levels of Grb7 in 88%
      of stage IV patients vs only 18% in stage I patients. A corresponding increase
      was found in the in vitro migration of stage IV CLL cells in comparison to stage
      I cells. The statistically significant difference in the expression of Grb7
      between stage IV and stage I patients was preserved even when tested specifically
      in the ZAP70-positive group (P<0.01). These findings show that Grb7 levels
      reflect the severity of the disease, and may be used, in conjunction with ZAP70,
      to predict disease progression.

PMID- 15470490
TI  - Identification of a survivin-derived peptide that induces HLA-A*0201-restricted
      antileukemia cytotoxic T lymphocytes.

PMID- 15470491
TI  - Prediction of relapse of acute myeloid leukemia in allogeneic transplant
      recipients by marrow CD34+ donor cell chimerism analysis.

PMID- 15470492
TI  - TCRB gene rearrangements in childhood and adult precursor-B-ALL: frequency,
      applicability as MRD-PCR target, and stability between diagnosis and relapse.
AB  - Using the multiplex PCR tubes of the BIOMED-2 Concerted Action, TCRB gene
      rearrangements were detected in 35% of childhood (n=161) and adult (n=172)
      precursor-B-ALL patients (Vbeta-(Dbeta)-Jbeta in 25%; Dbeta-Jbeta in 15%). The
      presence of TCRB rearrangements showed a significant relation with age (highest
      frequency of 46% between 5 and 10 years of age) and the presence of TEL-AML1
      transcripts, and was associated with relatively high frequencies of IGK-Kde,
      TCRG, and Vdelta2-Jalpha rearrangements. In 62 out of 65 patients with Southern
      blot-detected Vbeta-(Dbeta)-Jbeta and/or Dbeta-Jbeta rearrangements, at least one
      TCRB gene rearrangement was detected by PCR. Based on combined Southern blot and
      PCR analysis, oligoclonal TCRB gene rearrangements were observed in only 12% of
      patients. Analysis of paired diagnosis and relapse samples (n=26) showed that 20
      out of 24 (83%) Vbeta-(Dbeta)-Jbeta rearrangements and eight out of 14 (57%)
      Dbeta-Jbeta rearrangements remained stable. Using real-time quantitative PCR, a
      quantitative range < or =10(-4) was obtained in 64% of TCRB gene rearrangements
      and in 86% of cases a sensitivity < or =10(-4) was obtained. In conclusion, TCRB
      gene rearrangements occur in 35% of precursor-B-ALL patients and are relatively
      stable and sensitive PCR targets for detection of minimal residual disease,
      particularly if this concerns complete Vbeta-(Dbeta)-Jbeta rearrangements.

PMID- 15470493
TI  - Extramedullary manifestation of a donor-derived acute myeloid leukemia in a liver
      transplant patient.

PMID- 15470494
TI  - TGFbeta-mediated activation of Smad1 in B-cell non-Hodgkin's lymphoma and effect
      on cell proliferation.
AB  - We have previously reported an overexpression of Smad1 in follicular lymphoma
      (FL) cells, which are characterized by the t(14;18) bcl2/IgH translocation. Smad1
      is commonly involved in bone morphogenetic protein but not in tumor-transforming
      growth factor beta (TGFbeta) signaling pathways. This study focuses on Smad1
      signaling pathway in non-Hodgkin lymphoma cells including follicular or large
      cell lymphoma cells. Our results support the notion that phosphorylation of Smad1
      is mediated by TGFbeta present in the microenvironment and occurs in FL in vivo.
      Using an in vitro coculture system mimicking interactions between stroma cells
      and FL cells, we found that both the cell partners release TGFbeta at a
      sufficient concentration to activate Smad pathways in the malignant cells. This
      Smad1 activation involves TGFbetaRII but not ALK-1 receptors, and does not
      compete with the Smad2 pathway. Moreover, proliferation assays performed on
      lymphoma cells expressing wild-type or mutated Smad1, or in which endogenous
      Smad1 level was decreased by gene silencing, strongly supported that
      overexpression and activation of Smad1 modifies the biological response of
      lymphoma B cells to TGFbeta family members. This work opens new insights into
      aberrant Smad pathways and their pathophysiological role in FL and in other non
      Hodgkin lymphomas.

PMID- 15470496
TI  - Defining the position of the switches between replicative and bypass DNA
      polymerases.
AB  - Cells contain specialized DNA polymerases that are able to copy past lesions with
      an associated risk of generating mutations, the major cause of cancer. Here, we
      reconstitute translesion synthesis (TLS) using the replicative (Pol III) and
      major bypass (Pol V) DNA polymerases from Escherichia coli in the presence of
      accessory factors. When the replicative polymerase disconnects from the template
      in the vicinity of a lesion, Pol V binds the blocked replication intermediate and
      forms a stable complex by means of a dual interaction with the tip of the RecA
      filament and the beta-clamp, the processivity factor donated by the blocked Pol
      III holoenzyme. Both interactions are required to confer to Pol V the
      processivity that will allow it synthesize, in a single binding event, a TLS
      patch long enough to support further extension by Pol III. In the absence of
      these accessory factors, the patch synthesized by Pol V is too short, being
      degraded by the Pol III-associated exonuclease activity that senses the
      distortion induced by the lesion, thus leading to an aborted bypass process.

PMID- 15470498
TI  - Macrodomain organization of the Escherichia coli chromosome.
AB  - We have explored the Escherichia coli chromosome architecture by genetic
      dissection, using a site-specific recombination system that reveals the spatial
      proximity of distant DNA sites and records interactions. By analysing the
      percentages of recombination between pairs of sites scattered over the
      chromosome, we observed that DNA interactions were restricted to within
      subregions of the chromosome. The results indicated an organization into a ring
      composed of four macrodomains and two less-structured regions. Two of the
      macrodomains defined by recombination efficiency are similar to the Ter and Ori
      macrodomains observed by FISH. Two newly characterized macrodomains flank the Ter
      macrodomain and two less-structured regions flank the Ori macrodomain. Also the
      interactions between sister chromatids are rare, suggesting that chromosome
      segregation quickly follows replication. These results reveal structural features
      that may be important for chromosome dynamics during the cell cycle.

PMID- 15470497
TI  - Essential role of Smad3 in the inhibition of inflammation-induced PPARbeta/delta
      expression.
AB  - Wound healing proceeds by the concerted action of a variety of signals that have
      been well identified. However, the mechanisms integrating them and coordinating
      their effects are poorly known. Herein, we reveal how PPARbeta/delta (PPAR:
      peroxisome proliferator-activated receptor) follows a balanced pattern of
      expression controlled by a crosstalk between inflammatory cytokines and TGF
      beta1. Whereas conditions that mimic the initial inflammatory events stimulate
      PPARbeta/delta expression, TGF-beta1/Smad3 suppresses this inflammation-induced
      PPARbeta/delta transcription, as seen in the late re-epithelialization/remodeling
      events. This TGF-beta1/Smad3 action involves an inhibitory effect on AP-1
      activity and DNA binding that results in an inhibition of the AP-1-driven
      induction of the PPARbeta/delta promoter. As expected from these observations,
      wound biopsies from Smad3-null mice showed sustained PPARbeta expression as
      compared to those of their wild-type littermates. Together, these findings
      suggest a mechanism for setting the necessary balance between inflammatory
      signals, which trigger PPARbeta/delta expression, and TGF-beta1/Smad3 that
      governs the timely decrease of this expression as wound healing proceeds to
      completion.

PMID- 15470499
TI  - NSCL-1 and NSCL-2 synergistically determine the fate of GnRH-1 neurons and
      control necdin gene expression.
AB  - To study the role of the bHLH genes NSCL-1 and NSCL-2 in the development of GnRH
      1 neurons, we have generated compound mutant mice. Mutant animals die at birth
      and show a virtually complete absence of GnRH-1 neurons in the posterior parts of
      the brain at E18.5 and an aberrant morphology of the remaining GnRH-1 neurons in
      the anterior parts of the brain indicating that NSCL-1 and NSCL-2 might
      concomitantly control differentiation/migration of GnRH-1 neurons in a cell
      autonomous manner. To gain further insights into this process, we screened for
      NSCL target genes using DNA array hybridization and detected necdin, which is
      deleted in the human Prader-Willi syndrome phenotypically resembling the NSCL-2
      mutation. Using chromatin immunoprecipitation and site-directed mutagenesis of
      the necdin promoter, we demonstrate that NSCLs together with additional cofactors
      directly control transcription of the necdin gene. NSCL-dependent control of
      necdin expression might be instrumental for proper neuronal cell differentiation
      and enable GnRH-1 neurons to migrate.

PMID- 15470500
TI  - TI-VAMP/VAMP7 is required for optimal phagocytosis of opsonised particles in
      macrophages.
AB  - Phagocytosis relies on extension of plasmalemmal pseudopods generated by focal
      actin polymerisation and delivery of membranes from intracellular pools. Here we
      show that compartments of the late endocytic pathway, bearing the tetanus
      neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP/VAMP7), are
      recruited upon particle binding and undergo exocytosis before phagosome sealing
      in macrophages during Fc receptor (FcR)-mediated phagocytosis. Expression of the
      dominant-negative amino-terminal domain of TI-VAMP or depletion of TI-VAMP with
      small interfering RNAs inhibited phagocytosis mediated by Fc or complement
      receptors. In addition, inhibition of TI-VAMP activity led to a reduced
      exocytosis of late endocytic vesicles and this resulted in an early blockade of
      pseudopod extension, as observed by scanning electron microscopy. Therefore, TI
      VAMP defines a new pathway of membrane delivery required for optimal FcR-mediated
      phagocytosis.

PMID- 15470501
TI  - Inefficient degradation of truncated polyglutamine proteins by the proteasome.
AB  - Accumulation of mutant proteins into misfolded species and aggregates is
      characteristic for diverse neurodegenerative diseases including the polyglutamine
      diseases. While several studies have suggested that polyglutamine protein
      aggregates impair the ubiquitin-proteasome system, the molecular mechanisms
      underlying the interaction between polyglutamine proteins and the proteasome have
      remained elusive. In this study, we use fluorescence live-cell imaging to
      demonstrate that the proteasome is sequestered irreversibly within aggregates of
      overexpressed N-terminal mutant Huntingtin fragment or simple polyglutamine
      expansion proteins. Moreover, by direct targeting of polyglutamine proteins for
      proteasomal degradation, we observe incomplete degradation of these substrates
      both in vitro and in vivo. Thus, our data reveal that intrinsic properties of the
      polyglutamine proteins prevent their efficient degradation and clearance.
      Additionally, fluorescence resonance energy transfer is detected between the
      proteasome and aggregated polyglutamine proteins indicative of a close and stable
      interaction. We propose that polyglutamine-containing proteins are kinetically
      trapped within proteasomes, which could explain their deleterious effects on
      cellular function over time.

PMID- 15470502
TI  - Structure of the MutL C-terminal domain: a model of intact MutL and its roles in
      mismatch repair.
AB  - MutL assists the mismatch recognition protein MutS to initiate and coordinate
      mismatch repair in species ranging from bacteria to humans. The MutL N-terminal
      ATPase domain is highly conserved, but the C-terminal region shares little
      sequence similarity among MutL homologs. We report here the crystal structure of
      the Escherichia coli MutL C-terminal dimerization domain and the likelihood of
      its conservation among MutL homologs. A 100-residue proline-rich linker between
      the ATPase and dimerization domains, which generates a large central cavity in
      MutL dimers, tolerates sequence substitutions and deletions of one-third of its
      length with no functional consequences in vivo or in vitro. Along the surface of
      the central cavity, residues essential for DNA binding are located in both the N-
      and C-terminal domains. Each domain of MutL interacts with UvrD helicase and is
      required for activating the helicase activity. The DNA-binding capacity of MutL
      is correlated with the level of UvrD activation. A model of how MutL utilizes its
      ATPase and DNA-binding activities to mediate mismatch-dependent activation of
      MutH endonuclease and UvrD helicase is proposed.

PMID- 15470503
TI  - Regulated communication between the upstream face of RNA polymerase and the beta'
      subunit jaw domain.
AB  - We used bacteriophage T7-encoded transcription inhibitor gene protein 2 (gp2) as
      a probe to study the contribution of the Escherichia coli RNA polymerase (RNAP)
      beta' subunit jaw domain--the site of gp2 binding--to activator and ATP
      hydrolysis-dependent open complex formation by the sigma(54)-RNAP. We show that,
      unlike sigma(70)-dependent transcription, activated transcription by sigma(54)
      RNAP is resistant to gp2. In contrast, activator and ATP hydrolysis-independent
      transcription by sigma(54)-RNAP is highly sensitive to gp2. We provide evidence
      that an activator- and ATP hydrolysis-dependent conformational change involving
      the beta' jaw domain and promoter DNA is the basis for gp2-resistant
      transcription by sigma(54)-RNAP. Our results establish that accessory factors
      bound to the upstream face of the RNAP, communicate with the beta' jaw domain,
      and that such communication is subjected to regulation.

PMID- 15470504
TI  - Reorganisation of an RNA polymerase-promoter DNA complex for DNA melting.
AB  - Sigma factors, the key regulatory components of the bacterial RNA polymerase
      (RNAP), direct promoter DNA binding and DNA melting. The sigma(54)-RNAP forms
      promoter complexes in which DNA melting is only triggered by an activator and ATP
      hydrolysis-driven reorganisation of an initial sigma(54)-RNAP-promoter complex.
      We report that an initial bacterial RNAP-DNA complex can be reorganised by an
      activator to form an intermediate transcription initiation complex where full DNA
      melting has not yet occurred. Using sigma(54) as a chemical nuclease we now show
      that the reorganisation of the initial sigma(54)-RNAP-promoter complex occurs
      upon interaction with the activator at the transition point of ATP hydrolysis. We
      demonstrate that this reorganisation event is an early step in the transcription
      initiation pathway that occurs independently of RNAP parts normally associated
      with stable DNA melting and open complex formation. Using photoreactive DNA
      probes, we provide evidence that within this reorganised sigma(54)-RNAP-promoter
      complex, DNA contacts across the 'to be melted' sequences are made by the
      sigma(54) subunit. Strikingly, the activator protein, but not core RNAP subunits,
      is close to these DNA sequences.

PMID- 15470505
TI  - Activation of IKKalpha target genes depends on recognition of specific kappaB
      binding sites by RelB:p52 dimers.
AB  - IkappaB Kinase (IKK)alpha is required for activation of an alternative NF-kappaB
      signaling pathway based on processing of the NF-kappaB2/p100 precursor protein,
      which associates with RelB in the cytoplasm. This pathway, which activates
      RelB:p52 dimers, is required for induction of several chemokine genes needed for
      organization of secondary lymphoid organs. We investigated the basis for the
      IKKalpha dependence of the induction of these genes in response to engagement of
      the lymphotoxin beta receptor (LTbetaR). Using chromatin immunoprecipitation, we
      found that the promoters of organogenic chemokine genes are recognized by
      RelB:p52 dimers and not by RelA:p50 dimers, the ubiquitous target for the
      classical NF-kappaB signaling pathway. We identified in the IKKalpha-dependent
      promoters a novel type of NF-kappaB-binding site that is preferentially
      recognized by RelB:p52 dimers. This site links induction of organogenic
      chemokines and other important regulatory molecules to activation of the
      alternative pathway.

PMID- 15470507
TI  - [Current status of combined vaccines].

PMID- 15470506
TI  - Rac regulation of chemotaxis and morphogenesis in Dictyostelium.
AB  - Chemotaxis requires localized F-actin polymerization at the site of the plasma
      membrane closest to the chemoattractant source, a process controlled by Rac/Cdc42
      GTPases. We identify Dictyostelium RacB as an essential mediator of this process.
      RacB is activated upon chemoattractant stimulation, exhibiting biphasic kinetics
      paralleling F-actin polymerization. racB null cells have strong chemotaxis and
      morphogenesis defects and a severely reduced chemoattractant-mediated F-actin
      polymerization and PAKc activation. RacB activation is partly controlled by the
      PI3K pathway. pi3k1/2 null cells and wild-type cells treated with LY294002
      exhibit a significantly reduced second peak of RacB activation, which is linked
      to pseudopod extension, whereas a PTEN hypomorph exhibits elevated RacB
      activation. We identify a RacGEF, RacGEF1, which has specificity for RacB in
      vitro. racgef1 null cells exhibit reduced RacB activation and cells expressing
      mutant RacGEF1 proteins display chemotaxis and morphogenesis defects. RacGEF1
      localizes to sites of F-actin polymerization. Inhibition of this localization
      reduces RacB activation, suggesting a feedback loop from RacB via F-actin
      polymerization to RacGEF1. Our findings provide a critical linkage between
      chemoattractant stimulation, F-actin polymerization, and chemotaxis in
      Dictyostelium.

PMID- 15470508
TI  - [Rifaximin].

PMID- 15470509
TI  - [Coverage of the 23-valent pneumococcal vaccine in those older than 64 years of
      age in the region of Castellon and Valencia, Spain].
AB  - The different serotypes of Streptococcus pneumoniae isolated from adults aged
      over 64 years in the Valencia and Castellon health region of Spain from June 1999
      to December 2003 were analyzed. A total of 163 strains were evaluated; 58.3% were
      invasive, 47.24% were from respiratory source, and 4.9% were from exudates. The
      greatest percentage of samples was obtained from the group of patients aged 65 to
      75 years (60.7%), while the lowest percentage was obtained from the group of
      patients aged over 85 years (10.4%). In the latter group, 53% of the strains were
      invasive and 29.4% were isolated from sputum. A total of 21 serotypes were
      identified, with the most common (> 3%) being: serotype 3 (22.1%); serotype 19
      (12.9%); serotype 6 (12.3%); serotype 9 (8.6%); serotype 14 (10.4%); serotype 23
      (8%); serotype 29 (3.7%); and serotype 18 (3.1%). Serotype 3 was the most common
      serotype found in all samples, with the exception of exudate, while serotype 23
      was not isolated in blood. In this population group, the coverage of the 23
      valent vaccine was 88.4%. Serotypes not included in this vaccine but isolated
      from invasive samples were serotypes 16, 24, 29 and 35. No changes were observed
      in serotype distribution over the 4-year period of the study. However, it is
      necessary to continue epidemiological monitoring to determine whether serotype
      substitution occurs.

PMID- 15470510
TI  - [Bibliometric analysis of the Spanish Journal of Chemotherapy (1996-2000)].
AB  - A bibliometric study of the output of Spanish scientific research into
      antimicrobial and antiparasitic chemotherapy was carried out, based on articles
      published in the Spanish Journal of Chemotherapy from 1996 to 2000. The 20 issues
      of the journal corresponding to the 5-year period studied were analyzed using the
      main indicators for bibliometry: article typology; output; Bradford's Law and
      Lotka's estimation; collaboration index; institutional origin; geographic
      location; subject; and advertising. The majority of the articles were original,
      and a small group of high-output authors and an appropriate level of contribution
      were identified. The greatest percentage of scientific output was from the
      autonomous regions of Madrid and Valencia. The majority of studies included in
      the analysis were hospital-based and the most researched topic was antimicrobial
      drugs. A reduction in the amount of advertising was noted.

PMID- 15470511
TI  - [Evaluation of the Phoenix system for identifying and determining the
      susceptibility of clinical isolates. Comparative study with the Microscan
      system].
AB  - The Phoenix system (BD Diagnostic Systems), a rapid ID/AST system, was compared
      with the MicroScan WalkAway-40 system for accuracy of identification and
      antimicrobial susceptibility test results. The 327 bacterial isolates, were
      comprised of 191 Gram-negative bacilli (187 Enterobacteriaceae and 4 Aeromonas
      spp.) and 136 Gram-positive cocci (27 Staphylococcus aureus, 53 coagulase
      negative staphylococci, 45 enterococci and 11 beta haemolytic streptococci). The
      overall rate of agreement between the two systems for species level
      identification was 95.8% and 96.3% for Gram-negative bacilli and Gram-positive
      cocci, respectively. Enterococcus and Streptococcus species both achieved a 100%
      rate of species level agreement. The genus level agreement was >99% overall.
      Arbitration of the 8 Gram-negative bacilli disagreements resolved with 7 in
      agreement with the Phoenix identification. For the 5 Gram-positive cocci
      disagreements, 3 resolved in agreement with Phoenix. Overall, 3688
      antimicrobial/organism combinations were evaluated in both systems. For Gram
      negative isolates, the rate of essential agreement for the MICs was 98.5%, while
      the categorical agreement rate was 95.9%. Arbitration of 13 Gram-negative
      disagreements resolved with 11 in agreement with the Phoenix system. For
      Staphylococcus spp. and Enterococcus spp. isolates, the essential agreement rates
      were 96.4% and 99% respectively. Categorical agreement rates for both genera were
      94.7% and 96.1%, respectively. Arbitration of 5 staphylococci disagreements
      resolved with 2 in agreement with Phoenix system. Our results show that the
      Phoenix system is a rapid and reliable system for both identification and
      antimicrobial susceptibility testing of common clinical isolates.

PMID- 15470512
TI  - [Epidemiological study and effect on antimicrobial use in the genus Acinetobacter
      in a university hospital].
AB  - In recent years, bacteria of the genus Acinetobacter have gradually been gaining
      epidemiological importance. This is due to the fact that they have been emerging
      as opportunistic pathogens causing a great number of nosocomial infections, and
      due to their multiresistance to antimicrobial agents, which limits treatment
      options. This study aimed to determine the epidemiological importance of isolates
      of the genus Acinetobacter at the Clinical University Hospital of Salamanca,
      Spain. The identification and susceptibility of Acinetobacter was determined
      using the Pasco automated system for Gram-negative bacteria MIC/ID 6J. Clinical
      and epidemiological data were obtained from the clinical history. During the
      study period it was found that A. anitratus was the most frequently isolated
      species (56%). The origin of the bacteria was mainly nosocomial (70%), and it was
      most prevalent in the ICU.

PMID- 15470513
TI  - [Susceptibility of Enterococcus genus to new antimicrobial agents].
AB  - The aim of this study was to determine the prevalence of resistance to different
      antibiotics in 109 clinical strains of Enterococcus isolated consecutively in
      hospital over a four-month period in 2002. The strains were identified by species
      using the semiautomatic system Microscan walk away 40 (Dade Behring) and the
      API20 STREP system (Biomerieux). Three different methods for the susceptibility
      study were used: Sensititre, E-test and disc diffusion. The percentage of
      Enterococcus faecalis and Enterococcus faecium isolated was 92% and 8%,
      respectively. The following resistance to Enterococcus faecalis was detected:
      erythromycin (53%), telithromycin (36%), penicillin (2%), ampicillin (1%),
      vancomycin, teicoplanin and linezolid (0%), high level resistance to streptomycin
      (51%) and gentamicin (32%). A high percentage of strains resistant to penicillin
      and ampicillin was detected in E. faecium (six of nine strains). For two species,
      high susceptibility to linezolid and glycopeptides was found.

PMID- 15470514
TI  - [A study of clinical response to antibiotic treatment in subjects with chronic
      bacterial prostatitis].
AB  - A study was carried out on the clinical response to antibiotics in 105 patients
      with chronic bacterial prostatitis. Two groups of patients were compared in a
      retrospective study. The results of rectal examination, ultrasound scan,
      microbiological analysis, and response to different antibiotic therapy regimens
      were compared. There was a high incidence of perineal-testicular pain and sexual
      potency reduction; prostate congestion and pain on rectal examination were
      frequently reported. All the patients had positive microbial cultures, with Gram
      negative microorganisms being predominantly isolated. Following the
      administration of different antibiotic therapy regimens, symptoms either
      disappeared or diminished, irrespective of whether positive cultures remained. A
      poorer clinical response was observed in patients with positive prostate
      ultrasound and rectal examination, and with isolated Gram-negative bacilli. No
      differences were observed between either group in clinical response to different
      antimicrobial regimens.

PMID- 15470515
TI  - [Current therapeutic perspectives for sepsis].

PMID- 15470516
TI  - [Antimicrobial susceptibility of no-O1 Vibrio cholerae strains isolated from
      patients in Cuba].

PMID- 15470517
TI  - [Recommendations for the appropriate use of anti-TNFalpha therapy in patients
      with psoriatic arthritis. Italian Rheumatology Society].

PMID- 15470518
TI  - [The diabetic hand].
AB  - Diabetes mellitus is a chronic metabolic condition characterized by persistent
      hyperglycaemia with resultant morbidity and mortality related to its
      microvascular and macrovascular complications. In addition diabetes is also
      associated with several musculoskeletal disorders of the hand, that can be
      debilitating. There is increased incidence of these abnormalities in patients
      with type 1 and type 2 diabetes compared with the general population, related to
      disease duration but not to the age or sex. Typical diabetes associated hand
      condition include the palmar flexor tenosynovitis, Dupuytren's contracture,
      syndrome of limited joint mobility, carpal tunnel syndrome, Charcot arthropathy
      and reflex sympathetic dystrophy. Maintaining good glycaemic control by exercise,
      diet and drugs improves or prevents the development of these hand rheumatic
      condition. In this brief report we review the rational therapeutic approach to
      these disorders.

PMID- 15470519
TI  - [B lymphocyte stimulator (BLyS) and monocytes: possible role in autoimmune
      diseases with a particular reference to rheumatoid arthritis].
AB  - Recently, a new member of the TNF family, BLyS, was identified. This protein,
      synthesized by myeloid cell lines, specifically interacts with B lymphocytes and
      increases their life-span. BLyS was studied in the murine models of some
      autoimmune diseases and it was demonstrated that it has a key role in the B
      lymphocyte system homeostasis and in the relation between chronic inflammation
      and autoimmunity. Analysis of BLyS plasma levels in Systemic Lupus Erythematosus,
      Sjogren's Syndrome and Rheumatoid Arthritis (RA) has shown that BLyS is higher in
      a group of patients than in the controls. In RA, BLyS correlates with the disease
      activity, in particular, with the swollen joints count; so, at least part of the
      chronic rheumatoid synovitis could be the epiphenomenon of the B cells activation
      driven by monocyte-macrophage population. More studies are necessary to
      understand the role of BLyS in the interaction between the monocyte and the B
      lymphocyte in some autoimmune disease and the possible usefulness of this
      cytokine as a diagnostic or prognostic marker and/or therapeutic target.

PMID- 15470520
TI  - [Hyper-IgD syndrome and other hereditary periodic fever syndromes].
AB  - Hereditary periodic fever syndromes are a group of systemic disorders
      characterized by recurrent attacks of systemic inflammation (autoinflammation)
      without infectious or autoimmune cause. The hyper-IgD syndrome (HIDS) is a rare
      autosomal recessive inflammatory disorder characterized by recurrent fever,
      increased serum IgD (normal value < 100 U/ml) and generalized inflammation
      (lymphadenopathy, arthralgias/arthritis, abdominal complaints, skin rash, and
      headache). The attacks persist during the entire life although frequency and
      severity tend to diminish with age. HIDS is caused by specific mutations in the
      gene encoding mevalonate kinase, resulting in depressed enzymatic activity. At
      present the therapy for the syndrome is only supportive. Other than HIDS, other
      hereditary systemic inflammatory disorders have been described: the Familial
      Mediterranean Fever, the tumour necrosis factor receptor associated periodic
      syndrome (TRAPS), a disease related to the mutations of one of the TNF receptors,
      the Familial Cold Urticaria and the Muckle-Wells syndrome. The differential
      diagnosis with other causes of periodic fever is crucial for assessing
      appropriate management and treatment.

PMID- 15470522
TI  - [Role for familial and genetic features in the therapeutic response of psoriatic
      arthritis].
AB  - AIM OF THE STUDY: To analyze PsA patients with and without a familiar
      distribution for Ps and PsA, in order to better evaluate the genetic data, to
      verify the existence of different expression of the disease and finally to define
      the susceptibility to treatment in these patients. MATERIALS AND METHODS: 230 PsA
      patients were selected for familiar or sporadic distribution of the disease and
      were evaluated for the main clinical, demographic, radiological and laboratory
      features, as well as for the ongoing treatments. In each patient HLA class I
      (A,B,C) and II (DRB1, DQB1) antigens were typed with PCR-SSP method while MICA-A
      exon 5 microsatellite typing was performed by heteroduplex analysis in 122
      subjects. RESULTS: A familiar distribution for Ps and PsA was found in 68
      patients (29.6%) although only two patients had familiarity for PsA. In the
      familiar PsA group the male prevalence was significantly higher respect to the
      sporadic one (p<0.001) and the more frequently involved relative was the father
      (28%). Mean age (p<0.006) and age at onset of Ps (p<0.004) and PsA (p<0.014) were
      significantly lower in familiar respect to sporadic PsA. Between the two groups
      no difference was found concerning the articular involvement, the radiological
      findings, the disease activity (including number of painful/swollen joints), the
      inflammatory laboratory parameters (including ESR and CRP) and genetic aspects,
      including the frequencies of MICA-A alleles that were analysed in 30 patients
      with the familiar form and in 92 with the sporadic one. In the follow-up the
      therapeutic response to any evaluated treatment adopted for PsA did not show any
      significant difference in the two groups. All these results were confirmed even
      when the patients in the two groups were matchable for sex, age and disease
      duration. CONCLUSION: Our results confirm that familiar PsA is characterized by
      an early onset of the disease and by a male and fatherly predominance respect to
      the sporadic form, although the clinical-radiologic findings, the genetic typing
      and the therapeutic response do not permit us to identify any particular subset.

PMID- 15470521
TI  - Apoptosis and necrosis increase antigenicity of proteins recognized by
      antinuclear antibodies.
AB  - OBJECTIVE: Present study addresses the issue whether apoptosis and necrosis
      increases the antigenicity of proteins recognized by antinuclear antibodies.
      MATERIAL AND METHODS: HEp-2 cells were cultured in standard conditions; apoptosis
      was induced by camptothecin and necrosis by mercuric chloride. Protein
      antigenicity of cell extracts was tested onto nitrocellulose membranes and probed
      with positive or negative sera for antinuclear antibodies by a luminescent-dot
      ELISA system. RESULTS: Apoptotic changes in HEp-2 cells appeared by 24 hours of
      camptothecin exposure, meanwhile the necrotic features become visible earlier.
      Luminescence was significantly superior in ANA positive sera than in ANA negative
      controls. Antinuclear antibody sera recognized better the antigens from the
      apoptotic and necrotic cells than controls without chemical treatments.
      CONCLUSIONS: Apoptosis and necrosis increase the ANA binding by better
      availability of intracellular antigens, or by disclosing cryptic epitopes.

PMID- 15470523
TI  - [Epidemiology and risk factors in osteoarthritis: literature review data from
      "OASIS" study].
AB  - Ostheoarthritis (OA) is a social disease characterized by pain, inflammation and
      stiffness due to an involvement of articular cartilage, soft tissues and bone. OA
      is the most common rheumatic disease, every age can be affected but prevalence
      increases dramatically with age with a greater incidence in subjects between 40
      and 50 years of age. Hip OA has an important correlation with weight, genetic
      factors, sex, previous traumas, occupational factors and age. People older than
      35 have a prevalence of hip OA of 10.8% that becomes 35.4% in people older than
      85. Knee OA has a great correlation with weight ,life style and physical
      activity. An Italian study demonstrated that the prevalence of this kind of OA is
      highest in subjects older than 65 that becomes 44% in people older than 80. In
      this report we explain the results of a study conducted in the South of Italy
      called the OstheoArtrithis Southern Italy Study (OASIS) that involved 456 doctors
      and 1782 patients of three different regions. The mean age of these patients was
      66.3 years and we evaluated prevalence of hip, knee, hand and spine OA and
      correlated it to sex, age, weight and BMI. We also evaluated what kind of drugs
      were used for these patients. Knee OA is the most common subset of OA, the one
      that requires the highest number of examinations and the one that causes the
      greatest disability. The most common used drugs are Fans and Coxibs.
      Condroprotectors were not used much, probably because they are not considered to
      be very effective.

PMID- 15470524
TI  - [The treatment of recurrent uveitis with TNF-alpha inhibitors].
AB  - OBJECTIVE: Uveitis is a severe manifestation of rheumatic diseases since it can
      lead to visual impairment and even blindness. Ocular involvement is frequently a
      clinical challenge because its occurrence often requires changes of the
      therapeutic strategy. There are growing evidence that tumor necrosis factor alpha
      (TNFalpha) inhibitors may be an effective treatment of refractory uveitis.
      Purpose of this study was to evaluate the efficacy and safety of TNFalpha
      blocking agents in patients with seronegative spondylo-arthropathies (SNSA) and
      Behcet disease (BD) associated relapsing uveitis. METHODS: Five consecutive
      patients with chronic or relapsing uveitis were prospectively studied. Two
      patients with SNSA had recurrent anterior uveitis and three patients had BD
      associated uveitis (one anterior, two posterior uveitis). All of the patients
      were taking systemic and topical corticosteroids and three of them were also
      treated with DMARDs (methotrexate, cyclosporine, sulphasalazine) without clinical
      benefit. Four patients received infliximab, an anti-TNFalpha monoclonal antibody,
      at a dosage of 5 mg/kg body weight and one patient was treated with etanercept, a
      TNFalpha receptor p75-Fc fusion protein, at a dosage of 25 mg twice weekly.
      RESULTS: Both infliximab and etanercept induced a marked improvement in uveitis
      and none relapse was observed throughout all the study. Systemic corticosteroids
      were progressively tapered and stopped in all patients. Also methotrexate and
      sulphasalazine were discontinued, while cyclosporine dose has been reduced by
      30%. No side effects were observed. CONCLUSIONS: Therapy with TNFalpha blockers,
      infliximab and etanercept, was effective and safe in the treatment of rheumatic
      disease associated uveitis. A complete remission was achieved even in patients
      with severe steroid resistant uveitis. Further controlled studies on larger
      number of patients are needed to better define the different forms of ocular
      involvement that can benefit from the therapy with TNFalpha inhibitors.

PMID- 15470525
TI  - [Italian consensus on Eular 2003 recommendations for the treatment of knee
      osteoarthritis].
AB  - The recommendations for the management of osteoarthritis (OA) of the knee firstly
      proposed by the EULAR in 2000, have been updated in 2003. One of the most
      important objectives of the expert charged to provide these recommendations was
      their dissemination. Thus, the information generated may be used by each
      individual country to produce their own set of management guidelines and
      algorithms for treatment in primary care. The Italian Society of Rheumatology
      (SIR) and the Italian League against Rheumatism (LIMAR) have organised a
      Consensus on the EULAR recommendations 2003 with the aim to analyse their
      acceptability and applicability according to our own experience and local
      situations in the Italy. The results of this Consensus have demonstrated that a
      large majority of the EULAR recommendations are endorsed by the Italian experts.
      Furthermore, the final document of the Italian Consensus clearly indicated the
      need that specialists involved in the management of knee OA strongly encourage
      the dissemination of the EULAR 2003 recommendations also in Italy.

PMID- 15470526
TI  - [Femoral and humeral head osteonecrosis in a patient with hypofibrinolysis and
      hyperhomocysteinemia. A case report and a review of the literature].
AB  - Osteonecrosis is a disease characterized by the death of marrow and bone tissues.
      All bones may be affected, most commonly those of the hip, knee, shoulder, ankle
      as well as the small bones of the hands and feet. When the disease involves a
      weight-bearing joint there is a significant risk that subarticular fracture may
      develop leading to disabling arthrosis and requiring, therefore, arthroplasty
      surgery. Osteonecrosis typically affects patients in their third, fourth and
      fifth decades of life and is associated with many factors including other
      diseases and co-morbidities. Multifocal osteonecrosis is defined according to the
      involvement of at least three separated anatomic sites. We describe the case of a
      young man with osteonecrosis of the shoulder and hip joints which required total
      arthroplasty. Among biochemical investigations, an increase in the plasminogen
      activator inhibitor type 1 (PAI-1) levels associated with mild
      hyperhomocysteinemia was present. Another finding was the HLA B27, without signs
      of spondyloarthropathies. In patients with osteonecrosis, especially if
      multifocal, a careful medical history, a complete physical examination and some
      biochemical investigations, particularly those related to thrombophilia and
      hypofibrinolysis, should be performed.

PMID- 15470527
TI  - [Thumb troubles in rheumatoid arthritis].
AB  - Thumb involvement may play a relevant role in inducing a severe functional
      impairment in rheumatoid arthritis. The aim of this sonographic vignette is to
      show the value of sonography in detailing anatomic changes involving the thumb
      during a phase of active synovitis. The patient was a 50-year old man who
      presented with a 3-year history of rheumatoid arthritis. He complained of a 4
      week history of a marked recrudescence inflammatory thumb involvement associated
      with clinical signs of carpal tunnel syndrome. Sonographic images were obtained
      with a real-time ultrasound system equipped with a 13 MHz linear transducer.
      Sonographic examination on longitudinal dorsal scan of the metacarpophalangeal
      joint of the thumb showed a moderate joint cavity widening with two evident bone
      erosions, one at the metacarpal head and the other one at the basis of the
      proximal phalanx. The longitudinal volar scan of the first metacarpophalangeal
      joint confirmed the presence of synovitis detecting a marked joint cavity
      widening, with aspect of synovial proliferation. The flexor pollicis longus
      tendon was severely involved (marked tendon sheath widening, synovial
      proliferation, loss of the normal homogeneous fibrillar echotexture, and a large
      intratendinous tear). Sonography allowed the depiction of a wide range of
      otherwise undetectable pathologic changes in the standard clinical setting.

PMID- 15470528
TI  - [Some historical considerations on the inflammatory theory of atherosclerosis].
AB  - In the past 20 years several clinical and experimental observations have led to
      the hypothesis that an inflammatory response can trigger some key processes
      during the development of atherosclerosis. Here we briefly review, from the
      historical viewpoint, the inflammatory theory of atherosclerosis, as proposed by
      the Berliner pathologist Rudolf Virchow in the XIX century. Contrary to this
      hypothesis, in the same period the Viennese Karl von Rokitansky recognized blood
      dyscrasia (particularly fibrin-induced alterations) as the promoting factor in
      the process of atherogenesis. Moreover, we outline the relationship between
      atherosclerosis and arthritis, by reporting some passages from two scientific
      works published in the late XIX century, the former by the Italian Achille De
      Giovanni ("Sull'arterite. Sue forme cliniche e sua patogenesi", 1882) and the
      latter by the French Theophile Guyot ("L'arthritis. Maladie Constitutionnelle",
      1890).

PMID- 15470529
TI  - Wilson's Disease: a challenge of diagnosis. The 5-year experience of a tertiary
      centre.
AB  - BACKGROUND: Because molecular diagnosis is considered impractical and no
      patognomonic features have been described, diagnosis of Wilson's disease (WD)
      using clinical and biochemical findings is still challenging. PATIENTS AND
      METHOD: We analysed predictive factors for the diagnosis in 55 patients with WD
      diagnosed in our centre between 1st January 1999 and 1st April 2004. All patients
      presented predominant liver disease classified as: 1) asymptomatic, found
      incidentally, 2) chronic hepatitis or cirrhosis, or 3) fulminant hepatic failure.
      Diagnosis was considered as classic (two out of the three following criteria: 1)
      serum ceruloplasmin < 20 mg/dl, 2) the presence of Kayser-Fleischer rings and/or
      3) hepatic copper > 250 mg/g dry weight liver tissue), and non-classic (clinical
      manifestations plus laboratory parameters suggesting impaired copper metabolism).
      The association between the predictive factors and non-classic diagnosis was
      assessed based on the level of statistical significance (p value<0.05) associated
      with the chi-squared test in contingency tables. Multivariate analysis was
      performed by logistic regression using SPSS 10. RESULTS: There were 31 males
      (56.3%) and 24 females (43.7%) with the mean age at diagnosis of 20.92 +/- 9.97
      years (4-52 years); 51 patients (92.7%) were younger than 40 years. Asymptomatic
      WD was diagnosed in 14 patients (25.4%), chronic liver disease due to WD in 29
      patients (52.8%) and fulminant hepatic failure in 12 patients (21.8%). The
      classic diagnosis was made in 32 patients (58.18%). In the univariate analysis
      the non-classic diagnosis was associated with: age>18 years (p=0.03), increased
      copper excretion (p<0.0001), Coombs-negative hemolysis (p=0.03), absence of
      neurological manifestations (p<0.0001). Multivariate analysis identified age over
      18 years, increased urinary copper, and isolated hepatic involvement as
      independent predictors. CONCLUSION: In clinical practice, WD should be considered
      also in patients who do not fulfil classic criteria. Independent factors
      associated with non-classic diagnosis were age over 18 years, increased
      cupruresis and isolated liver disease.

PMID- 15470530
TI  - Risk factors for colorectal cancer: an epidemiologic descriptive study of a
      series of 333 patients.
AB  - AIM: The purpose of the research was to evaluate several risk factors for colonic
      neoplasia and to institute a specialized colorectal cancer (CRC) registry in the
      3rd Medical and Surgical Clinics Cluj-Napoca. MATERIAL AND METHODS: The study
      comprised 333 patients,155 women, mean age 61.32 +/- 12.42 years and 178 men,
      mean age 64.31 +/- 10.39 years, admitted to the 3rd Medical Clinic and 3rd
      Surgical Clinic Cluj-Napoca and diagnosed with CRC between January 2001 -
      September 2003. The diagnosis was made on the basis of clinical, endoscopical and
      histopathological findings. Age, geographical patterns, tumor location, family
      history, personal history and several lifestyle factors: dietary habits (intake
      of fat and red meat), long term smoking (more than 20 years), heavy alcohol
      consumption were analyzed. Evaluation was made using family history and
      epidemiologic lifestyle questionnaires. RESULTS: CRC occurred more frequently in
      the 7th decade. There was a strong correlation between age and CRC development.
      In the 5th decade, females developed CRC more frequently than males. The median
      age for developing right-sided tumors was significantly higher in males. Patients
      living in an urban area were dominant (69%). Family history was present in 1/3 of
      females and 1/4 of males. Personal history of colon polyps was more common in
      men, particularly among smokers for more than 20 years and among those with an
      excessive intake of fat. The cholecystectomized women had an increased frequency
      of sigmoidian tumors. All the patient's information was included in a specialized
      colon cancer registry. CONCLUSION: High fat intake and cigarette smoking favour
      colon polyp development. CRC development and location of the tumor are associated
      with an older age (in men) and personal history of cholecystectomy (in women).
      Inheritance was significant in our study group.

PMID- 15470531
TI  - Screening for functional tumor suppressor activity in pancreatic cancer.
AB  - Pancreatic cancer has a well-known reputation as one of the leading causes of
      cancer deaths worldwide. Thus, acquisition of efficient approaches and markers
      for accurate detection at the earlier stages of the disease should be
      prioritized. We have been focusing on tumor suppressor genes (TSGs) activity in
      pancreatic cancer to find effective methods for its genetic diagnosis and/or
      treatment. In this study, we utilized the technique of micro-cell-mediated
      chromosome transfer (MMCT) to introduce a normal copy of human chromosome 18
      individually into some pancreatic cancer cells. Subsequently, the tumorigenic
      ability of the resulting hybrids was assessed in vitro and in vivo. In vitro
      growth of the hybrid clones was significantly delayed as compared to the parental
      cells. This was paralleled by the hybrid cells promotion of invasive carcinomas
      in nude mice at a significantly lower rate and with a longer latency than the
      parental tumor cells. This study provides evidence that MMCT is an efficient tool
      for screening of tumor suppressor activity in pancreatic cancer. The functional
      data emerging from this study bring into sharp relief the implication of
      chromosome 18 as a putative location for new TSG(s), yet to be identified in this
      region.

PMID- 15470532
TI  - Relevance of mast cells and hepatic lobule innervation to liver injury.
AB  - Chronic liver diseases commonly result in liver fibrosis, and eventually liver
      cirrhosis. In the last decade, a new theory explaining liver fibrosis has been
      established. Accordingly, the development of liver fibrosis due to chronic liver
      diseases is thought to be mediated by inflammatory cells. They release fibrogenic
      mediators such as transforming growth factors (TGF)-beta, which are considered to
      be responsible for the activation and transformation of fat-storing cells.
      Recently, the involvement of mast cells and peripheral and autonomic nervous
      system in the fibrogenesis has been suggested. This study was aimed to establish
      the presence and distribution of mast cells and nerve fibers in the rat liver in
      the light of their implication in liver inflammatory and fibrotic disorders. Mast
      cells and afferent (sensory) fibers were detected immunohistochemically. An
      immunofluorescent method was applied to demonstrate tryptase and serotonin (SER)
      in the mast cells, while the primary sensory neuronal processes were identified
      by using antibodies against their marker calcitonin gene-related peptide (CGRP)
      and the proinflammatory mediator substance P (SP). The portal tracts and fibrous
      septa contained numerous mast cells, which exhibited strong immuno-reactivity to
      tryptase and SER. SER-positive nerve fibers were also found. It is generally
      accepted that no nerve fibers are present in the hepatic lobules, but the current
      investigation clearly demonstrates availability of CGRP-, SP, and SER
      immunoreactive nerve fibers there. Our results indicate that in the rat liver
      portal tracts and hepatic lobules there are numerous mast cells, sensory and
      autonomic nerve fibers, which may be involved in liver injury by the inflammatory
      mediators they release.

PMID- 15470533
TI  - Pharmacokinetic interaction study between ranitidine and metoclopramide.
AB  - The pharmacokinetics of metoclopramide in healthy volunteers was evaluated to
      determine if previously repeated doses of ranitidine inhibit the metabolism of
      the gastrointestinal prokinetic drug. Metoclopramide 20 mg (tablets) in
      combination with ranitidine 150 mg (tablets) were administered to 14 healthy
      human volunteers in a two treatment study design, separated by 5 days in which
      the ranitidine alone was administrated in single p.o. doses twice daily. Plasma
      concentrations of metoclopramide were determined during a 24 hour period
      following drug administration. Metoclopramide plasma concentrations were
      determined by a validated RP-HPLC method. Pharmacokinetic parameters were
      calculated with compartmental and non-compartmental analysis. In the two periods
      of treatments, the mean peak plasma concentrations Cmax were 44 ng/ml
      (metoclopramide alone) and 49.2 ng/ml (metoclopramide and ranitidine). The time
      taken to reach the peak, Tmax, was 1.15 hrs, and 1.21 hrs, respectively. The
      total areas under the curve (AUC) was 314.3 ng.hr/ml and 354.06 ng.hr/ml,
      respectively. The half-life (T 1/2) was 5.6 hr and 6.7 hr. A statistically
      significant difference was observed for both AUC and half-life of metoclopramide
      when administered alone or after 5 days of treatment with ranitidine. The
      experimental data proved the pharmacokinetic interaction between ranitidine of
      metoclopramide, and suggest monitoring adverse effects in patients.

PMID- 15470534
TI  - Chronic acalculous gallbladder disease: outcomes of treatment by laparoscopic
      cholecystectomy.
AB  - BACKGROUND AND AIMS: The diagnosis and treatment of chronic acalculous
      gallbladder disease (CAGD) remains controversial. Laparoscopic cholecystectomy
      (LC) is increasingly accepted as the treatment of choice for this condition. The
      purpose of this study was to analyse the outcomes from LC for CAGD and to
      identify potential prognostic factors. METHODS: We retrospectively analysed 54
      patients with a clinical diagnosis of CAGD. All patients underwent LC. The
      outcomes were evaluated at 12 months. Outcomes from surgery were graded on a
      predetermined scoring system (score 1-6) reflecting the effect of surgery on
      symptomatology. Histopathological analysis was systematically performed on the
      resection specimens. RESULTS: Post-operatively, 90.8% of patients (49/54) were
      satisfied with the operation (outcome score 1-2). A pathological abnormality was
      detected in 40 patients (74.1%). Of those in whom no abnormality detected on
      histopathological examination, LC achieved a successful outcome (score 1-2) in
      85.7% of patients (12/14). The worst outcomes (score 5-6) were observed in 2
      patients with a pathological abnormality of the gallbladder. For the 5 patients
      with outcome scores of 3 to 6 (poor outcome), the mean duration of symptoms was
      7.1 months compared to 18.2 months for patients with score of 1 and 2 (good
      outcome). CONCLUSIONS: There is no significant correlation between outcomes from
      LC for CAGD and the existence of a definable underlying pathology (p>0.05).
      Patients with long-standing symptoms were more likely to benefit from LC
      (p=0.039). LC is an appropriate treatment option for CAGD.

PMID- 15470535
TI  - Barrett's Esophagus.
AB  - Barrett's esophagus is an alteration of the esophageal epithelium, regardless of
      length, evidenced by endoscopic examination (protrusion of the gastric mucosa
      into the esophagus in the shape of a flame) and confirmed by histological
      examination of the bioptic samples (intestinal metaplasia with mucosecretory
      cells). It develops following long-term gastro-esophageal reflux (GER). The
      documented risk factors are: long-term GER (duration more than 5 years), age over
      50 years, male sex, Caucasian race, aggressiveness of the refluxed material,
      individual susceptibility of the esophageal mucosa to the refluxed material. The
      carcinogenic risk is 30 times higher than in the general population. Treatment
      targets the acid reflux, with proton pump inhibitors (PPI), prevention of
      carcinogenesis with cyclooxygenase 2 inhibitors, ablation of the metaplastic area
      by laser, plasma-argon mucosectomy, or photodynamic therapy and antireflux
      surgery.

PMID- 15470536
TI  - Molecular prognostic factors in rectal cancer.
AB  - The prognosis of patients with rectal cancer can be assessed mainly on the basis
      of clinical and pathological factors among which the pTNM stage is the most
      valuable indicator. Recently, different combinations of molecular markers, which
      have prognostic significance, have been identified in an attempt to establish a
      "molecular staging" that would permit - along with the histopathological staging 
      taking optimum therapeutic decisions in colorectal cancer. An example in this
      respect is the attempt to classify patients with rectal cancer stage II (N-) with
      a view to administering adjuvant treatment to the risk subgroup. The prognostic
      role of various factors (biological, genetic, molecular, etc.) was classified
      into four categories according to their predictive value. This paper reviews the
      most recent research, especially regarding the factors in the third category in
      order to assess their impact upon prognosis and to identify the most valuable
      factors that could change the therapeutic algorithm of rectal cancers in the
      future. However, more statistical studies are necessary before these factors can
      become the basis of new therapeutic strategies or prognostic evaluations in
      rectal cancer.

PMID- 15470537
TI  - Surgical therapy of colorectal metastases -- state of the art.

PMID- 15470538
TI  - Blue rubber bleb nevus syndrome: case report and literature review.
AB  - Blue Rubber Bleb Nevus Syndrome ( BRBNS) is a rare disorder characterized by
      multiple cutaneous venous malformations in the skin and gastrointestinal tract
      associated with intestinal hemorrhage and iron deficiency anemia. Other organs
      may also be involved. BRBNS has a potential for serious or fatal bleeding. The
      causes of this syndrome are unknown. Its most common presentation is in the form
      of sporadic cases, but dominant autosomal inheritance has been described.
      Although it was first recognized by Gascoyen in 1860, only one hundred years
      later did Bean further describe these lesions and coined the term BRBNS. A
      MEDLINE search yielded about 200 case reports published till 2003. We present a
      case of this syndrome diagnosed in a 16- year - old patient with both upper and
      lower gastrointestinal bleeding. He had severe anemia and venous swellings on the
      trunk. Similar lesions were found in the stomach, bowel and on his foot. In
      addition, we review the available literature on the epidemiology, clinical
      features, associated conditions, diagnosis and treatment.

PMID- 15470539
TI  - Right adrenal abscess -- an unusual complication of acute apendicitis.
AB  - Acute appendicitis represents one of the most frequent abdominal emergencies
      encountered in everyday surgical practice. Local infectious complications are not
      unusual and retroperitoneal abscesses after acute retrocaecal appendicitis have
      been previously described. The authors present the case of a 22-years-young
      female patient, admitted for a right iliac fossa abscess, secondary to gangrenous
      appendicitis. A right adrenal mass 35/40 mm was revealed during preoperative
      ultrasound evaluation, which evolved in an adrenal abscess that spontaneously
      drained 10 days after appendectomy and retrocecal drainage. Adrenal abscesses are
      exceptionally rare, with only a few cases being reported in the literature, but
      none of these after acute appendicitis.

PMID- 15470540
TI  - Ruptured hydatid cyst of the liver with biliary obstruction: presentation of a
      case and review of the literature.
AB  - The case of a 66 year old woman admitted with a picture of jaundice acute
      cholangitis is reported. Ultrasonography showed a dilatation of intrahepatic bile
      ducts, gallbladder hydrops with several stones, enlarged common bile duct (CBD)
      with hyperechoic material inside and a cystic tumor with hydatid features. With a
      strong suspicion of a hydatid cyst ruptured in the biliary tree with biliary
      obstruction, endoscopic cholangiopancreatography was performed. The diagnosis was
      confirmed by endoscopic retrograde cholangiopancreatography and the hydatid
      membranes were extracted from the CBD with subsequent clinical improvement. The
      second step of treatment comprised the surgical cure of the cyst and
      cholecystectomy. The data from the literature are finally presented with a
      special emphasis on the ultrasound diagnosis and the endoscopic treatment.

PMID- 15470542
TI  - Residual accessory spleen after splenectomy in liver cirrhosis with portal
      hypertension.

PMID- 15470541
TI  - Hematemesis as a presenting symptom of lung cancer with synchronous metastases to
      the esophagus and stomach. A case report.
AB  - A rare case of upper gastrointestinal hemorrhage due to synchronous metastases to
      the esophagus and stomach from an asymptomatic lung cancer is reported. A 51-year
      old white man presented with hematemesis and an emergency endoscopy revealed
      submucosal tumorous lesions with central ulcerations in the esophagus and
      stomach. A needle aspiration biopsy revealed the presence of cellular
      proliferation of adenocarcinoma, which led to the diagnosis of lung cancer, along
      with a chest radiograph revealing a tumor in the right middle lung field. The
      importance of conducting an upper gastrointestinal endoscopic examination for
      staging of patients with lung cancer is stressed.

PMID- 15470543
TI  - [Benzodiazepines: mental health and social health].

PMID- 15470544
TI  - [Benzodiazepines: Consequences on memory in the elderly].
AB  - Studies conducted with a healthy voluntary population with a unique medication
      indicate that benzodiazepines (BZD) are known to induce memory deficits. However,
      this group does not correspond to the population usually using these medication
      on a regular basis, knowingly the elderly people. Few studies have been conducted
      with this target population to determine the impact of BZD on their memory.
      However, some findings suggest that there are important consequences on the
      functioning of memory of the elderly people taking BZD. The current data go as
      far as suggesting that BZD exacerbate memory deficits in the elderly. This could
      even constitute a risk factor that could hasten cognitive decline and thus
      increase development of dementia.

PMID- 15470545
TI  - [Clinical advice facilitating withdrawal of benzodiazepines].
AB  - This article summarizes a clinical approach aiming at facilitating withdrawal of
      benzodiazepines. The authors underline the importance of a medical evaluation in
      order to identify reasons that have led to the use and maintaining of a
      pharmacological treatment and to better understand the reasons and motivation of
      the patient to cease his medication. During this assessment, it is important to
      inform the patient to gradually reduce his medication in order to diminish the
      severity of side effects expected during withdrawal. A step by step approach
      where the patient actively participates in decisions is proposed to reduce the
      anxiety, but also to prevent the patient from taking unilateral initiatives that
      would go against an approach aiming at optimizing the success of withdrawal. Some
      clinical vignettes are presented to illustrate the steps of withdrawal as well as
      situations where reducing or even stopping medication is difficult.

PMID- 15470546
TI  - [Benzodiazepine withdrawal in patients with generalized anxiety disorder:
      efficiency of a behavioral and cognitive intervention].
AB  - Benzodiazepine medication is often prescribed for the short-term treatment of
      generalized anxiety disorder. The chronic nature of generalized anxiety disorder
      entails a prolonged use of these psychotropic medication on several months and
      several years, entailing also a psychological and physical addiction. The current
      study aims at determining if the combination of a behavioral and cognitive
      therapy and gradual withdrawal facilitate interrupting the use of benzodiazepine
      in patients with generalized anxiety disorder. In total, five participants have
      received the combined intervention according to an experimental protocol of
      unique case with multiple levels. Four among them have completed the withdrawal
      plan and have demonstrated important clinical improvements. Data collected during
      the 3rd and 6th month indicate the preservation of therapeutic gain. These
      results suggest that behavioral and cognitive therapy facilitates stopping the
      use of benzodiazepine medication in patients with generalized anxiety disorder by
      significantly reducing anxious symptoms.

PMID- 15470547
TI  - [Cognitive-behavioral treatment of insomnia and its use during withdrawal of
      hypnotic medication].
AB  - Insomnia is a widespread health problem that often leads to the use of hypnotic
      medication. Among the available pharmacological agents to treat insomnia,
      benzodiazepines (BZD) present some undesirable effects, entailing risks of
      tolerance and dependence, and increased risk of automobile accidents, falls and
      fractures in the elderly. Cognitive-behavioral treatment (CBT) of insomnia, which
      focuses on psychological and behavioral factors that play a role in maintaining
      sleep-related problems, is efficient to improve sleep in the elderly who suffer
      from primary insomnia. This treatment may represent an alternative to
      pharmacotherapy or again be complementary during discontinuation of hypnotic
      medication. The CBT of insomnia may include different components such as stimulus
      control, sleep restriction, relaxation, cognitive restructuring and sleep
      hygiene. For people who are dependent to BZD or other hypnotic medication, a
      supervised tapering based on attaining successive objectives is generally added
      to the CBT of insomnia.

PMID- 15470548
TI  - [Developing an Instrument evaluating expectations related to benzodiazepine
      withdrawal].
AB  - Discontinuing the use of benzodiazepine medication can represent a difficult task
      for some people. High rates of relapses are associated with attempts to stop
      their use. However, it remains difficult to explain why some people fail in their
      efforts. The current knowledge suggests the involvement of a psychological
      component in the difficulty to stop benzodiazepine medication (BZD). Expectations
      of people who consider stopping their medication has been mentioned as a possible
      explanation of the failure of the withdrawal process. However, no empirical study
      has examined the effect of these expectations on the appearance of symptoms
      during withdrawal or its outcome. This article presents the development of an
      instrument aiming at assessing personal expectations regarding discontinuation of
      benzodiazepine medication with individuals who suffer from anxiety. It presents
      preliminary data related to the clinical validity of items. From 50 initial
      items, 24 have been eliminated following a first test with some participants.
      Among 26 chosen items, it has been observed that 8 items (for example,
      nervousness/anxiety, cognitive capacities, mood) could discriminate between
      participants having succeeded and those having failed. Generally, it has been
      observed that participants who have succeeded had expectations that were
      significantly more positive than people who had failed in their attempt to stop.
      These preliminary results tend to support the hypothesis according to which
      negative expectations would harm the BZD withdrawal process. However, these
      results must be replicated with a greater number of participants.

PMID- 15470549
TI  - [Evaluation of a program to help discontinuation of benzodiazepines].
AB  - The efficacy of a new cognitive-behavioral group program to help discontinuation
      of benzodiazepines (PASSE) was evaluated by comparison to a group receiving only
      social support. Both programs lasted 20 weeks commencing with a preparatory
      period of one month and then tapering continually during 16 subsequent weeks
      until discontinuation. Forty-eight participants (24 in each condition) with a
      diagnosis of anxiety disorder took part in the study. These two active conditions
      were compared with a separate group of 41 people receiving standard tapering with
      physician counselling only. The results post-treatment supported the hypothesis
      that those receiving either of the two active treatments succeeded better in
      discontinuing benzodiazepines than those receiving the standard treatment. Among
      those completing the two active programs there was no difference in outcome
      between the social support and the cognitive behavioral (PASSE) group. However,
      when the rate of dropout was considered, the cognitive-behavioral group proved
      significantly superior than the social support group. The results suggest that a
      cognitive-behavioral program can help people wishing to discontinue
      benzodiazepines to psychologically tolerate the immediate effects of
      discontinuation.

PMID- 15470550
TI  - [Benzodiazepine use in the elderly: state of the knowledge].
AB  - This article reviews the literature concerning addiction to benzodiazepine (BZD)
      in the elderly population of 65 and over. While the negative consequences related
      to a prolonged use of BZD are well known, much less is known on the phenomenon of
      dependency to these substances in this population. There is still no consensus on
      the definition of the problem. The continuous use of BZD may be more problematic
      in the elderly for whom tolerance to chemical agents diminishes with age. The
      risk factors involved in the chronic use are an interactive combination between
      the characteristics of the elderly as well as the physicians who prescribe such
      medication. Paths of research to support a paradigmatic change are presented in
      order to improve the research in this field.

PMID- 15470551
TI  - [Anxiolytic, sedative and hypnotic medication use in the elderly living in the
      community: Developing a conceptual framework].
AB  - Inappropriate consumption of anxiolytic, sedative and hypnotic medication (ASH)
      in the elderly is an important public health issue. Almost 35 % of the elderly
      population living at home take these medications, approximately 206 days per
      year. According to Quebec data, people who are 65 and older take five times more
      ASH than people between 18 and 64. The use of ASH would not only be determined by
      the presence of symptoms, but also by psychosocial characteristics of the
      subjects. Moreover, several researchers have suggested that the family as well as
      the health system were environmental factors that could facilitate or inhibit
      consumption of these medications in the elderly. A conceptual framework is
      proposed to help specify more adequately the various explanatory hypotheses of
      this social health behavior and, consequently, better target interventions aiming
      at its modification.

PMID- 15470552
TI  - [Five cases of neonaticide in Quebec].
AB  - A neonaticide is the homicide of an infant that occurs during the first 24 hours
      after birth. This homicide is almost exclusively done by the mother. According to
      previous data, the parent who commits such homicide is a single woman, who
      usually conceals her pregnancy and delivers secretly either at home or in the
      workplace and panics at this very moment. Five vignettes are selected from the
      files of the Quebec Coroner. The cases are presented in order to verify if these
      women represent a homogeneous group, as research of the last thirty years has
      demonstrated. According to data for the period between 1986 and 1994, the
      deceased newborns are boys, and the teenage mothers have personalities that are
      characterized by immaturity. In this group, denial of pregnancy is a temporary
      state that may vary in depth among individuals. Moreover, they did not want to be
      pregnant. One older group of women experience separation anxiety at the time of
      commiting the neonaticide. Clinical and theoretical implications are discussed in
      link with these two sub-groups.

PMID- 15470553
TI  - [Rational motivation of drug injection and prostitution].
AB  - Homeless drug users and prostitutes constitute a population at risk for
      contracting and propagating AIDS. This study aims at understanding the paradox
      related to drug injection and prostitution among 21 homeless from Montreal. These
      behaviors are studied following the picoeconomic paradox of an apprehended
      desire. The results show that these homeless see drug injection as a self-reward
      motivated by imaginary emotional object, in spite of the known and dreaded
      consequences. Prostitution is described as a self-investment accessory to drug
      injection. This study concludes with reflections on AIDS prevention programs in
      relation with the needs of the homeless.

PMID- 15470554
TI  - [Psychological profile of adolescent girls victim of sexual abuse and under the
      protection of child services].
AB  - This study examines the symptoms of 30 adolescent girls who are under child
      protection care following sexual assault. In addition to describing the
      psychological profile of these adolescents, the study describes the sexual abuse,
      services received, and identifies factors that are likely to be linked to
      symptoms. Results show that adolescents present many psychological problems and
      that the majority experience distress necessitating clinical attention. Sexual
      abuses are at the extreme end of the large continuum reported in the literature
      and services are infrequent and irregular. Symptoms are associated with the time
      elapsed since the last sexual abuse and with services received. The discussion
      highlights the importance of adequacy between services and psychological profile
      of each adolescent while suggesting a model of recovery.

PMID- 15470555
TI  - [Sexual and physical abuse in women with severe mental disorder: a literature
      review].
AB  - In order to better understand women who suffer from severe psychiatric disorders,
      this literature review of 18 studies examines their experiences of sexual and
      physical abuse. It is apparent that people with severe mental disorder and more
      specifically women, are vulnerable to physical and sexual abuse. Homeless women
      with severe mental disorders are particularly vulnerable. The authors focus on
      links between reality and practice in the treatment of this clientele in both
      institutional and community settings.

PMID- 15470556
TI  - [The use of theatre as promoter of change in social skills].
AB  - This article presents a case study on the use of acting with six people suffering
      from severe and long-lasting psychotic state. The study aims at elaborating the
      hypothesis on the use of this activity in readaptation. The effect of expression
      therapy on the development of social skills has rarely been substantiated by
      empirical studies. The literature review points out a poor generalization of
      social skills following social skills training ; it also allows a description of
      the acting and its therapeutic potential. A qualitative methodology is applied to
      an investigation conducted in a psychiatric day center and uses the description
      of behavior before and after the program. The results indicate resemblances
      between the therapeutically acquired social skills and the social behavior from
      everyday life. The use of acting in therapy would contribute at the
      generalization of social skills.

PMID- 15470557
TI  - [Young patients with severe mental illness returning to school: results of a
      pilot project conducted in Montreal].
AB  - Schizophrenia generally appears at the beginning of adult life at a time when
      individuals have important academic choices to make for their professional
      future. Patients with schizophrenia suffer from cognitive deficits as well as
      positive and negative symptoms and experience disorganization. Schizophrenia is
      responsible for a high level of failure in obtaining a high school diploma, an
      important cause of social exclusion and low economic status. Twenty-seven
      students with severe mental health have been integrated in an educational program
      implemented in Montreal. Preliminary results indicate efficiency of the program
      with many students succeeding ministerial test. However, it is suggested that a
      ratio of 1/10 professor/students would be preferable in such special education
      class.

PMID- 15470558
TI  - [A few unresolved and frequent questions concerning anxiety and anxiety
      disorders].
AB  - The field of anxiety disorders shows a considerable evolution in the last decades
      concerning the overall conceptualization of the disorders and concerning their
      treatment. However many questions remain open. For instance, what is the
      importance of anxiety disorders in terms of public health? What is their
      influence on other factors affecting populations' health, e.g. substance abuse,
      and especially smoking? Questions also remain concerning the underlying
      mechanisms, whether biological or psychological. For instance, is it possible to
      identify cognitive schemas leading to pathological anxiety? What are the
      physiological manifestations of the hypervigilance and hyperreactivity that are
      described clinically? Despite the successive classifications, some issues are
      unsettled concerning the delimitation of anxiety disorders. For instance, do
      obsessive-compulsive disorders belong to anxiety disorders or preferably to a
      different family of mental disorders constituting a spectrum of obsessive
      compulsive disorders? Several practical issues remain open for clinicians: what
      is the importance of specific therapeutic factors in cognitive-behavioral
      therapies? Is there a psychoanalytical method and a psychopharmacological therapy
      specific to anxiety disorders? Concrete questions also deserve attention in
      relation with therapeutic modalities. Are group treatments superior to individual
      ones? What is the role of emotion in cognitive-behavioral treatment? Is it useful
      to associate self-regulation strategies like meditation? Do self-help
      organizations, that are numerous and helpful in that field, have a role
      concerning psychotherapy?

PMID- 15470559
TI  - [How hypervigilance and hyperreactivity clinically described in anxiety expressed
      physiologically?].
AB  - Anxious people often show a particular attentional focus towards potentially
      threatening stimuli. Like any other emotion, anxiety goes along with
      physiological reactions, which may be more or less noticeable, and may impair
      behavior and physical wellness. In view of the psychophysiological reactions
      related with anxiety and anxiety disorders, it seems important to examine
      potential correlations between psychophysiological activity and the phenomena of
      hypervigilance. In fact, selective psychophysiological activation has repeatedly
      been found as a reaction to pathology-specific threatening stimuli in patients
      with anxiety disorders, whereas their psychophysiological responses appeared
      often to be blunted when they were submitted to neutral stimuli.

PMID- 15470560
TI  - [Obsessive compulsive disorders: part of anxiety disorders or another family of
      mental disorders?].
AB  - This article reviews four separate conceptions of obsessional compulsive disorder
      (OCD). The first is a movement disorder, the second is part of a wider OCD
      spectrum including impulsive and compulsive disorders, the third is currently
      classified in the DSM-IV-TR, as an anxiety disorder, and the fourth and final
      view that OCD is a belief disorder and forms a continuum with other belief
      disorders such as delusional ideation. Although there is support for the four
      viewpoints, and OCD is distinct from movement, anxiety and impulsive disorders,
      it seems reasonable to conceptualize OCD as a belief disorder which creates
      anxiety as a consequence of the obsessional belief.

PMID- 15470561
TI  - [Early maladaptive schemas predisposing anxiety].
AB  - This article examines the links between anxiety and early maladaptive schemas as
      elaborated by Young. These schemas have been divided in three categories: schemas
      that already include anxiety in their definition; schemas that refer to a
      relational loss or crisis; schemas linked to a potential loss of self-integrity.
      These three categories influence the expression of anxiety. The link between
      anxiety and schemas is not always clear and often require further clinical
      judgment. Finally, the schema focused approach appear to favor a better
      understanding of symptoms in the context of the individual's structural
      organization.

PMID- 15470562
TI  - [Anxiety disorders: an issue for public health?].
AB  - The enhancement of mental health is becoming an increasingly important public
      health issue. Anxiety disorders are the most common mental problems. In light of
      the scope of the problem, public health has the mandate to continuously monitor
      the evolution of these disorders and to ensure that the health care system serves
      the population appropriately, in terms of service availability, accessibility,
      continuity and effectiveness. Moreover, public health ensures that prevention and
      promotion programs are put in place to contend with risk factors and encourage
      individuals to adopt habits that promote good mental health. This article
      describes public health interventions in relation to anxiety disorders in
      Montreal.

PMID- 15470563
TI  - [Are anxiety disorders associated to a particular addiction to smoking? Stress,
      anxiety and nicotine addiction].
AB  - This paper describes the relationship between several types of anxiety disorders
      and tobacco use. Possible explanations of those relationships are presented.
      Nicotine probably modulates the function of pathways involved in stress response
      and anxiety in the normal brain, which results in alterations of anxiety levels.
      Anxiety disorders do not seem to be related to a particular form of tobacco
      consumption. However, smoking is more frequent in these patients and seems to be
      implicated in some of their coping strategies. Understanding neurobiological and
      behavioral mechanisms underlying the association between smoking and anxiety
      disorders may improve physician's ability to assist smokers in their efforts to
      quit.

PMID- 15470564
TI  - [Is there an approach of psychoanalytical inspiration specifically adapted to
      anxiety disorders?].
AB  - Psychoanalytic treatments have been relegated to a secondary status in the
      current recommendations concerning the treatment of anxiety disorders. This is
      due to the lack of controlled studies pertaining to these psychotherapies, as
      well as to the late adaptation of psychoanalysis to the contemporary trends of
      psychopathology and psychotherapy focusing on symptoms. The recent development of
      a manualized psychotherapy for the treatment of panic disorder, the Panic-Focused
      Psychodynamic Psychotherapy (PFPP), is a good example of such an adaptation
      (Milrod et al., 1997). PFPP appears to be effective (Milrod, 2001). This type of
      psychotherapy is probably neither more nor less effective than other forms of
      psychotherapy if one considers the results of empirical research on the
      comparative effectiveness of psychotherapies. The question formulated by the
      title of this paper is perhaps less central as is that of the nature of the
      active factors of the psychotherapeutic process.

PMID- 15470565
TI  - [What is the specific importance of therapeutic factors in the psychological
      treatment of social phobia?].
AB  - This article describes the psychological interventions developed or adapted
      specifically for the treatment of social phobia. Two main strategies have been
      identified : anxiety reduction and improvement of social functioning. Exposure
      and cognitive restructuring are the main procedures for anxiety reduction. For
      the improvement of social functioning, social skills training is the principal
      procedure. The outcomes on a short and long term basis are analyzed and compared
      to psychopharmacology. Tasks (homework) to be performed in real-life situations
      between sessions are considered as an essential element of all interventions.
      However, these tasks are guided by the different theoretical principles inherent
      to each approach.

PMID- 15470566
TI  - [What is the place of emotion in cognitive-behavioral approaches of obsessive
      compulsive disorders?].
AB  - The efficacy of behavioral techniques based on exposure and response prevention
      has been well validated in the treatment of obsessive-compulsive disorder.
      Nevertheless in a large proportion of patients the disease persists, among others
      due to refusal of the treatment or due to non-response. About one of two patient
      entering treatment seems therefore to possibly benefit from behavioral therapy
      (Ladouceur et al., 1999). Cognitive techniques may extend the behavioral
      approach, and may represent a more indirect and progressive method, and may
      improve patients' commitment in the therapy. However, the proportion of treatment
      resistant patients remains important. New techniques are therefore warranted in
      order to progress in the understanding and treatment of these patients. Emotion
      focused therapy could possibly represent an interesting approach based on the
      improvement of emotional awareness, the exploration and the cognitive
      restructuring of emotions. The different techniques are described throughout
      clinical case reports.

PMID- 15470567
TI  - [Do cognitive-behavioral group therapies in the treatment of anxiety disorders
      have an advantage over individual treatments?].
AB  - Group cognitive-behavior therapies in the treatment of anxiety disorders for
      adult psychiatric patients were historically developed on the basis of validated
      individual treatments. They have been widely employed and studied for social
      phobia, panic disorders, agoraphobia and obsessive-compulsive disorders, with
      generally positive results similar to those obtained with the corresponding
      individual methods. The cognitive-behavioural group treatments for generalized
      anxiety and posttraumatic stress disorders have not yet received sufficient
      validation. The results of evaluative research show that the format of the
      therapy (individual or group) does not appear to predict the outcome. Therefore
      an indication for an individual or a group therapy cannot be made on the basis of
      the diagnosis alone. It has to be based on other criteria, in particular
      economical, organisational or clinical. Group therapies can certainly offer
      advantages in comparison with individual procedures, even if they cannot always
      fit perfectly the specific needs of every patient. Indication has to be made
      individually, in order to allow the therapists to judge their patients'
      capacities and interest to participate in a group program.

PMID- 15470568
TI  - [Is there a specific pharmacological treatment for anxiety disorders? Summary of
      a controversy].
AB  - The acute pharmacological treatment of anxiety disorders is barely specific with
      the exception of the obsessive-compulsive disorder: it responds preferentially to
      potent serotoninergic antidepressants only. For all other anxiety disorders all
      antidepressants regardless of their mechanism of action could be equally
      efficient thanks to their common class effect and are considered to be the
      pharmacological treatment of first choice. Benzodiazepines that also share a
      common class effect are recommended as possible and temporary adjuvants.
      Augmentation strategies for the cases of refractory anxiety disorders are also
      non-specific: lithium, antipsychotics, anticonvulsants.

PMID- 15470569
TI  - [Does approach using "mindfulness" meditative exercises have a role to play?].
AB  - Mindfulness is the fundamental attentional stance underlying all streams of
      Buddhist meditative practice. It has been described as "paying attention in a
      particular way: on purpose, in the present moment, and nonjudgmentally." During
      the last years, mindfulness practice has been evaluated and introduced into
      several mental health treatments (Mindfulness Based Stress Reduction; Dialectical
      Behavior Therapy; Mindfulness Based Cognitive Therapy). In this paper, the author
      considers the mechanisms that may explain how mindfulness skills can lead to
      symptom reduction and behavior change in different emotional disorders and in
      anxiety disorders.

PMID- 15470571
TI  - [Group homes and the "not in my back yard" phenomenon (NIMBY)--it happened close
      to home: a pilot study].
AB  - Implementation of group homes often come up against the "Not in My Back Yard"
      (NIMBY) phenomenon. In order to better understand this phenomenon, this pilot
      study examines the experience of community residents in three borough where
      opposition to the implementation of group homes was encountered. Results reveal
      the underlying reasons for this problem as well as explore the negative impact of
      the presence of such group homes in the community. Finally, the author concludes
      that listening to citizens and acknowledging their concerns are essential to
      developing greater acceptance and a better support towards group homes.

PMID- 15470572
TI  - [Paradoxical situation in the organization of work: a threat for workers' mental
      health].
AB  - For the past decades, in a world of high competition, firms struggle to regain an
      advantage over foreign competition. Thus, new management trends, usually based on
      price reduction, high quality products and speed production are now part of
      strategic reorganization plans of high impact on work organization particularly
      in terms of large demands put on workers, and take a heavy toll on workers. Thus
      the incidence of mental health problems in the work place has risen sharply in
      recent years and currently counts as one of the leading causes of work
      absenteeism. A study based on the psychodynamic of work was conducted among
      machine operators working in a high-technology company in the aviation sector.
      Important management and technological transformations were recently introduced
      in the factory. The content analysis of the study shows that the work
      organization places the operator in a double bind situation. They are caught
      between an injunction where the capacity of making a high quality product is
      directly opposed to that demanding speed production. Moreover, severe and
      arbitrary sanctions are applied when the operators do not comply with either
      injunction. The operators are put in a deadlock situation that creates fear and
      anxiety. They are obliged to turn to defensive psychological strategies such as
      individualism and cheating. Those defensive strategies have negative impacts on
      social relationships.

PMID- 15470573
TI  - [Validation of the French version of the CTQ and prevalence of the history of
      maltreatment].
AB  - This study demonstrates that the five maltreatment scales in the long and short
      versions of the CTQ are valid and usable with French-speaking populations. It
      also shows emotional neglect to be the most common form of maltreatment in its
      general population sample, and physical neglect to be the least common. Physical,
      emotional and sexual abuse prevalences in the convenience sample roughly
      correspond to the rates generally obtained in non-clinical samples. Finally,
      women in the sample display greater co-occurrence of different forms of
      maltreatment, especially involving sexual abuse, than men.

PMID- 15470574
TI  - [Life events and trauma in chronic negligent mothers].
AB  - The present study examines more closely the chronic behaviors of maltreating
      mothers. Events that these mothers have experienced during childhood are
      examined, experiences including abuse, placement, separation, bereavement,
      rejection, neglect, lack of love and role reversal. Signs of unresolved trauma
      found in the discourse of mothers, such as dissociation, are also studied. It is
      proposed that negligent mothers from the chronic group will evoke more negative
      experiences and/or more intense negative experiences which occurred during
      childhood than the mothers from the transitory group. The chronic group will also
      show more signs of dissociation. From a six years follow-up study, a sample of 20
      mothers was recruited from the Child Protection Services, including the cases of
      10 chronic maltreating mothers and 10 transitory maltreating mothers. Two main
      measures were used: the Child Abuse Potential Inventory (CAPI) and the Adult
      Attachment Interview (AAI) (Main et Goldwyn, 1998). The experiences from
      childhood and complete discourse in AAI were analysed with the method used by
      Main et Goldwyn (1998). Non parametric analysis indicate that mothers from the
      chronic group evoke more negative and very negative childhood experiences than
      the mothers from the transitory group. Content analysis show that chronic
      maltreating mothers relate having gone through more potentially traumatic events
      such as foster care placements, separations and abuse. The analysis of the Adult
      Attachment Interview according to Main and Goldwyn's system demonstrate that the
      majority of the chronic maltreating mothers have two times more unresolved
      traumas.

PMID- 15470575
TI  - [The psychodynamic of work: object, epistemological considerations, concepts and
      theoretical premises].
AB  - This article describes the psychodynamic approach to work developed in the '70 in
      France by Christophe Dejours. It consists of an interdisciplinary approach that
      views the organization of work as both a source of pleasure and suffering as well
      as the origin of defensive strategies of individuals who strive to reconcile the
      demands of the workplace with personal efforts to protect their health. The
      psychodynamic approach is part of the comprehensive subjectivist paradigm based
      on a hermeneutic philosophy. The author's purpose is to make this approach more
      widely known by researchers who seek a better understanding of mental health
      problems that arise in the workplace.

PMID- 15470576
TI  - [The psychodynamic of work and the stress paradigm: a sound and useful
      complementarity in favor of the development of knowledge in the field of health
      at work].
AB  - This article describes the major similarities and differences between the
      approaches of psychodynamic of work and stress. It shows how the psychodynamic of
      work constitutes an interesting complementary approach to the stress paradigm in
      terms of development of knowledge of mental health at work.

PMID- 15470577
TI  - [The long march backward.... Essay on the psychology of the contemporary
      individual].

PMID- 15470578
TI  - [Brain dynamics according to Justo Gonzalo].

PMID- 15470579
TI  - Epidemiology of central nervous system tumors at the Instituto Nacional de
      Neurologia y Neurocirugia in Mexico City.
AB  - The purpose of this study was to determine the frequency of different Central
      Nervous System Tumors (CNST) diagnosed at the Instituto Nacional de Neurologia y
      Neurocirugia (National Institute of Neurology and Neurosurgery) from Mexico City
      over a 10-year period (1990 to 1999) by means of a hospital survey. This
      institute is a reference hospital that provides medical attention to a very high
      number of adult neurological patients every year (approximately 6,000 new
      patients per year besides emergency cases). From a total number of 2,041 CNST
      cases, we found that the most frequent tumors were those affecting the
      neuroepithelial tissue (32.8 %), followed by tumors of the anterior pituitary
      gland (26.2 %) and tumors of the meninges and similar tissues (24.1 %). In both,
      male and female patients the higher frequency of CNST was found in patients whose
      age ranged from 25 to 44 years, and CNST were slightly more frequent in women
      than in men. Most of the CNST patients lived in the southern districts of Mexico
      City, it could be because of the great number of people living in the southern
      districts of the city, or perhaps due to the presence of certain yet unidentified
      environmental carcinogenic substance in this area. Since CNST are among the more
      frequent malignant neoplasms, it is necessary to improve the registration system
      to include frequency, prevalence, incidence and mortality of these diseases in
      Mexico, in order to plan health policies like in developed countries.

PMID- 15470580
TI  - [Spanish contribution to the clinical development of eletriptan: an analysis of
      controlled studies].
AB  - INTRODUCTION: Eletriptan is a recently marketed second-generation triptan with a
      potent agonist activity on 5-HT1B/ 1D receptors. Our aim has been to analyze the
      specific results from the Spanish participation in phase IIIa and IIIb clinical
      trials vs placebo and compare them with the results obtained in the global
      clinical development of eletriptan. PATIENTS AND METHODS: Analysis of the results
      obtained in 40 centers in Spain (358 patients) vs global sample 4,677 patients)
      for the first migraine attack in 6 controlled clinical trials with eletriptan 40
      mg, eletriptan 80 mg and placebo. This ad hoc analysis was carried out for those
      treatment groups with more than 50 patients, which reduced the final number of
      patients from Spain to 250. RESULTS: The proportion of patients with relief at 2
      hours (main endpoint) in the Spanish sample was 22 %, 59 % and 67 % for placebo,
      eletriptan 40 mg and eletriptan 80 mg, respectively. These values were
      significantly higher (p < 0.05) than those of placebo and similar to those from
      the total sample. The proportion of pain free patients at 2 hours in the Spanish
      sample was 10 %, 36 % and 41 % for placebo, eletriptan 40 mg and eletriptan 80
      mg, respectively. These values were significantly better than those for placebo
      (p < 0.05) and about 15 %-20 % higher than those from the total sample.
      Recurrence rate in the Spanish sample was 50 %, 16 % and 25 % for placebo,
      eletriptan 40 and eletriptan 80 mg, respectively, and did not differ from that of
      the total sample. Sustained relief for the two eletriptan doses was 46 % for both
      eletriptan 40 and eletriptan 80, this being significant (p < 0.05) over placebo
      (11 %) for the Spanish sample and similar to that of the global sample. The
      results for other efficacy parameters, such as need of rescue medication,
      functional response at 2 hours, complete response for pain-freeness and
      acceptability followed a similar pattern. Eletriptan was, in general, well
      tolerated. Adverse events were slight-moderate in intensity, transient and were
      not different, either in profile or proportion, from those from the global
      sample. CONCLUSIONS: These results confirm eletriptan 40 mg and 80 mg as an
      excellent option for the symptomatic treatment of migraine in our setting.

PMID- 15470581
TI  - [Descriptive analysis of the e-mail list "Neurologia-RedIRIS"
      (http://listserv.rediris.es/neurologia.html): an active, plural instrument having
      scientific quality at the reach of the Spanish speaking neurology sector].
AB  - INTRODUCTION: In recent years, professional mailing-lists (PML) have experienced
      wide diffusion in the field of the medicine thanks to their educational and
      academic potential. In neurology and in Spanish, Neurologia list belonging to
      RedIRIS has played the lead in the history of PML. Since the year 1997, it has
      maintained approximately 200 persons related with neurology in communication and
      has exceeded more of 7,300 messages. MATERIAL AND METHODS: We analyzed
      retrospectively the activity recorded in the Neurologia PML between January and
      December 2003, recording variables related to the activity and scientific quality
      of the PML and to the origin and content of the messages. RESULTS: 758 messages
      were registered (2.07 messages/day; 3.73 messages/subscriber). 93 of 203
      subscribers (45.81 %) participated on at least one occasion. 83 % of the messages
      came from Spain, there being an inverse relationship between the neurologists
      relative endowment and degree of participation in the PML. The most frequent
      messages referred to clinical cases followed by debate of topics of management
      and scientific consultations. The scientific quality of Neurologia PML is
      comparable to other English language based PML analyzed based on the number of
      publications in Index Medicus and of the impact factor of its subscribers.
      CONCLUSION: Neurologia PML has reached a level of maturity and enjoys a critical
      mass and a number of subscribers of high scientific level that assures its
      immediate future. Besides its educational and consultation functions, it may
      become an opinion forum for the Spanish neurologists without their losing their
      independence or Latin-American vocation.

PMID- 15470583
TI  - [Modafinil and fatigue in multiple sclerosis].
AB  - Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis
      (MS) patients. This symptom's etiopathogenic mechanism, though not known, seems
      complex and multifactorial, and its therapeutic management is difficult.
      Different treatments have been tested in recent years, but a weak efficacy that
      may be limited in time has been observed. Recently, modafinil has been suggested
      as a possible treatment for fatigue in MS patients, although nowadays, the only
      use of modafinil approved by the Food and Drug Administration is narcolepsy.
      Modafinil, 2-([difenilmetil]sulfinil), acetamide is a state of wakeness promoter,
      and although its exact action mechanism is not known, it differs from other
      central nervous system stimulants because no dopaminergic activation is observed,
      and its action take place at the hypothalamic level. It is known that modafinil
      increases the proportion of high-frequency alpha waves and reduces delta and
      theta waves, increasing vigilance. Although few studies exist on modafinil in MS
      patients with fatigue, the results suggest this drug as a promising treatment,
      because of its efficacy and safety, and should encourage us to continue working
      in this area.

PMID- 15470582
TI  - [The neuroscientific work of Justo Gonzalo (1910-1986): the center syndrome and
      reversal metamorphopsia].
AB  - The Spanish neuroscientist Justo Gonzalo Rodriguez-Leal (Barcelona 1910, Madrid
      1986) carried out different studies on cerebral functions, highlighting those
      made in patients with encephalic injuries suffered during the Spanish civil war.
      His book "Investigaciones sobre la nueva dinamica cerebral. La actividad cerebral
      en funcion de las condiciones de excitabilidad nerviosa", published in two
      volumes (the first one in 1945 and the second one five years later), gathers some
      of his fundamental contributions, among which the so-called central syndrome
      stands out. A dominant parietal lesion (central) equidistant from the visual,
      sensorial and auditory projection areas can lead to diverse perceptive
      dysfunctions, among them inversions in visual, tactile and acoustic perception.
      As the lesion becomes more peripheral, the resulting defect will be more
      unisensorial and crossed, while when it approaches the central region, the
      disorders will be bilateral and polysensorial. Justo Gonzalo explained all these
      phenomena later by a gradient system.

PMID- 15470584
TI  - [Spanish adaptation of the European Guidelines on Cardiovascular Disease
      Prevention].

PMID- 15470585
TI  - [European Guidelines on Cardiovascular Disease Prevention in the Clinical
      Practice. Third work group of the european societies and other societies on
      cardiovascular disease prevention in the clinical practice].

PMID- 15470586
TI  - [Fascicular paralysis of the III cranial nerve].

PMID- 15470588
TI  - [Cerebellar degeneration associated with anti-Tr antibodies without Hodgkin's
      disease. Four years follow-up].
AB  - The presence of antineuronal anti-Tr antibodies is associated to paraneoplastic
      cerebellar degeneration due to Hodgkin's disease. The anti-Tr can become negative
      after successful and early treatment of the tumor, and there could even be
      remission of the cerebellar symptoms in some patients. There are few cases in
      which no tumor is found when there are anti-Tr. We report the case of a 66 year
      old man with a severe cerebellar syndrome and anti-Tr in serum detected by
      immunohistochemistry. After a 4 year follow-up, no underlying tumor has been
      found. In addition, anti-Tr spontaneously disappeared. The cerebellar
      degeneration persists and is incapacitating. This case suggests that in a few
      instances the origin of anti-Tr is not a tumor but another unknown cause.
      Alternatively the anti-Tr mediated immune response could have eradicated the
      underlying lymphoma.

PMID- 15470587
TI  - [Baroreflex failure after chemodectoma resection].
AB  - Baroreflex failure after chemodectoma resection We present a case of baroreflex
      failure secondary to a unilateral injury of the glossopharyngeal nerve. The
      patient was operated for a left-sided chemodectoma in the carotid body. Some
      months after surgery she started to report presyncopal episodes exacerbated by
      mental stress and when standing up. During these episodes, the patient presented
      hypertensive crises and tachycardia. However, blood pressure was below normal
      ranges at rest. The diagnosis was baroreflex failure secondary to unilateral
      injury of the glossopharyngeal nerve. The case reported herein illustrates the
      fact that the presence of a bilateral injury is not essential for the occurrence
      of this disorder.

PMID- 15470589
TI  - [Progressive encephalomyelitis with rigidity responsive to gabapentin: a
      pharmacological update].

PMID- 15470590
TI  - Medicinal chemistry-XVIIIth International Symposium. Part I. 15-19 August 2004,
      Copenhagen, Denmark & Malmo, Sweden.

PMID- 15470591
TI  - Medicinal chemistry-XVIIIth International Symposium. Part II. 15-19 August 2004,
      Copenhagen, Denmark & Malmo, Sweden.

PMID- 15470592
TI  - International Narcotics Research Conference-35th Meeting. Current developments in
      medicinal chemistry in the opioid field 17-24 July 2004, Kyoto, Japan.
AB  - Research in the opioid field underwent a lull in the 1990's but much new research
      has recently been stimulated, firstly by the cloning of all of the opioid
      receptors and then by the development of gene knockout mice and their phenotype
      characterization. These developments have led to a a reappraisal of the potential
      utility of opioid agonists and antagonists not only for the treatment of pain but
      also for mood-related conditions and peripheral indications. Medicinal chemistry
      groups are still moving the field forward, and the pharmaceutical industry
      continues to keep a watching brief. Opioids are no longer exclusively the
      province of pain scientists, and potential for treatment of limbic disorders,
      itch and addiction are only now beginning to be considered seriously.

PMID- 15470593
TI  - AIDS 2004-XV International Conference July 11-16, 2004, Gangkok, Thailand.
AB  - The headlines from the XV International AIDS Conference concerned political,
      economic and social controversies, but among the thousands of studies presented
      was evidence that progress is being made in finding treatments that may someday
      be able to control the AIDS epidemic, and not only in the world's wealthier
      nations.

PMID- 15470594
TI  - GPCR allosterism and accessory proteins: new insights into drug discovery, 17
      July 2004, Glasgow, Scotland.
AB  - This satellite meeting provided an insight into the current status and progress
      with GPCR allosterism and interacting accessory proteins. With one compound on
      the market (cinacalcet) and several others in clinical development (eg, targeting
      M1 and mGluR2), it is clear that targeting allosteric sites on GPCRs represents a
      valid approach to identifying novel drugs. Targeting allosteric sites may confer
      additional selectivity and permit conformational changes in GPCRs to enable
      disruption of large protein-protein interactions (eg, CCR5). Despite emerging
      research on the potential of interacting accessory proteins as drug targets,
      further research to understand these interactions are required before initiating
      focused drug discovery programs that specifically target GPCR-interacting
      proteins.

PMID- 15470595
TI  - American Society for Virology-23rd annual meeting. Vaccines and antiviral agents
      10-14 July 2004, Montreal Canada.

PMID- 15470596
TI  - Antibody World Summit 2004-SRI Conference 19-21 July 2004, Philadelphia, PA, USA.
AB  - Overall, the sessions were well attended and a lot of questions were asked. Two
      thirds of the speakers were from industry and the rest from academia. Of
      particular note, The academics presented cutting-edge science in the antibody
      discovery and development area. Business representatives from various therapeutic
      antibody companies discussed in detail various aspects and challenges of building
      a viable therapeutic antibody company.

PMID- 15470597
TI  - Federation of European Pharmacological Societies-fourth annual meeting. Part I.
      14-17 July 2004, Porto, Portugal.

PMID- 15470598
TI  - Federation of the European Pharmacological Societies-fourth annual meeting. Part
      II. 14-17 July 2004, Porto. Portugal.
AB  - The aims of this Federation of European Pharmacological Societies (EPHAR)
      meetings are to broaden the understanding of fundamental pharmacology. Rather
      than present clinically relevant novel therapeutics, most symposia and posters
      presented data exploring the role of receptors, transmitters and potential agents
      within a basic science framework. The opening plenary session was given by Sir
      James Black, and the main meeting revolved around parallel symposia and poster
      sessions. Most presenters gave a broad overview of the current understanding,
      with less emphasis on individual compounds, while others developed a theme
      exploring specific agonists/antagonists and experimental models.

PMID- 15470599
TI  - Metabolic Diseases Drug Discovery-Strategic Research Institute's Third
      International World Summit. PPAR and PTB1B modulators 26-27 July 2004, San Diego,
      CA, USA.

PMID- 15470600
TI  - Metabolic Diseases Drug Discovery-Strategic Research Institute's Third
      International World Summit. Dipeptidyl peptidase-IV inhibitors 26-27 July 2004,
      San Diego, CA, USA.
AB  - The majority of the presentations a the conference were on three highly sought
      after targets for type 2 diabetes mellitus, namely PTP1B, PPARs and DPP-IV,
      reflecting the current focus and trend in the industry. A couple of novel targets
      were discussed, including the potential of myostatin as a type 2 diabetes
      mellitus target and a novel GPCR target. While small molecules were dominant,
      several biological-based approaches were covered: antibody therapeutics and
      oligonucleotide-based approaches (ASO and siRNA). In searching for small-molecule
      leads, structure-based rational design and focused combination chemistry appear
      to produce better results than a random high-throughput approach over the entire
      chemical library. The biggest challenges for diabetes and obesity drugs remain
      similar to those mentioned in previous meetings: increasing specificity to reduce
      side effects and maintaining long-term effect while maintaining or increasing
      efficacy. Due to the tremendous interest of the pharmaceutical industry in
      metabolic disease drug development, our knowledge of food intake and metabolism
      regulation has increased exponentially. Overall, the prospect of better drugs
      for, and better control of, type 2 diabetes mellitus and obesity is promising.

PMID- 15470601
TI  - BioAsia Licensing and Deal-Making Summit-SRI Conference. Life science partnering
      and investment on the Pacific Rim 2-3 August, 2004, Coronado, CA, USA..
AB  - The Strategic Research Institute's inaugural BioAsia Licensing and Deal-Making
      Summit, co-organized by the BioMinerva Group, attracted industrial leaders in
      biotechnology and pharmaceuticals from both sides of the Pacific Ocean. Topics
      discussed at the 2-day conference spanned from trans-Pacific licensing and
      partnering trends led by Japan-US deals, the changing landscape of the Japanese
      pharmaceutical industry, and trans-Pacific partnering strategies to perspectives
      of Asia-Pacific markets and successful investment strategies. The emerging
      Chinese biotechnology and pharmaceutical industry was also covered prominently,
      including assessments of the Chinese market, discussions on intellectual
      property, regulatory and tax issues, as well as case studies of Sino-US
      collaborations and technology showcases from Chinese biotech companies.

PMID- 15470602
TI  - Bipolar depression: an overview.
AB  - Depressive episodes are significant in bipolar illness since patients can spend
      up to one-third of their lives in depression. Although the treatment of bipolar
      depression remains an understudied area, new data from randomized, controlled
      trials and naturalistic studies have expanded the range of treatments available.
      The main aim in the treatment of bipolar depression is the prevention of the
      patient switching to mania and cycle acceleration, and antidepressant therapy may
      be contraindicated because of the risk for switching. Guidelines for the acute
      treatment of bipolar depression emphasize treatment with a mood stabilizer, of
      which lithium has been the most thoroughly studied in randomized, controlled
      trials in acute bipolar depression. Lamotrigine has also demonstrated significant
      efficacy in recent studies and has been approved by the FDA.

PMID- 15470603
TI  - Vinflunine.
AB  - Pierre Fabre SA, in collaboration with Bristol-Myers Squibb Co, is developing
      vinflunine, a fluorinated vinca alkaloid, as a potential anticancer agent.

PMID- 15470604
TI  - Estrasorb.
AB  - Novovax Inc has developed and launched Estrasorb, a transdermally absorbed, micro
      encapsulated estradiol, as an estrogen replacement therapy for short-term use in
      the reduction of vasomotor symptoms in menopausal women. Estrasorb was launched
      in the US in April 2004.

PMID- 15470605
TI  - Is there a difference between diabetic and non-diabetic ITAs? Histomorphological
      and immunohistochemical examinations of internal thoracic arteries.
AB  - BACKGROUND: The relative resistance to arteriosclerosis of the internal thoracic
      artery is clinically valid. The aim of this study was to evaluate the graduation
      of intima and media fibrosis in ITA parts and to determine the extent of
      atherosclerosis using immunohistochemical methods related to patients' risk
      factors. METHODS: 227 distal ITA segments from 144 male and 83 female patients
      were examined. Mean age was 66.7 +/- 9.03 years. HE and Elastica van Gieson
      staining was performed to detect intima-/mediafibrosis. POPULATION: insulin
      dependent diabetes mellitus (idDM; n = 35), non-insulin-dependent diabetes
      mellitus (nidDM; n = 32), irradiation of the chest due to cancer (n = 27),
      control group with isolated hyperlipidemia, hypertension, peripheral vascular
      disease (n = 133). 12 ITA segments of each group were examined
      immunohistochemically using CD34, CD68, Tenascin, Collagen III, Collagen IV.
      RESULTS: Histomorphological examinations using HE and Elastica van Gieson
      stainings showed for idDM-ITAs no fibrosis in 57 %, slight fibrosis in 34 %,
      medium in 6 %, no severe, for nidDM-ITAs no fibrosis in 63 %, slight 31 %, medium
      3 %, severe 3 %, for ITAs after irradiation: no fibrosis in 37 %, slight in 62 %,
      no medium or severe fibrosis. Compared to the control group there was no
      statistically significant difference in diabetic ITAs. Immunohistochemical
      examinations, scored on a 0 - 3 basis with 0 being the lowest (no reaction), 3
      the highest (severe reaction), showed mostly no or slight reaction to CD34, CD68,
      Tenascin, and Collagen III for intima and media, with comparable results for
      diabetic or "irradiated" ITAs to those of the control group. The most distinct
      reaction (medium= 2), was detected for Collagen IV, a marker which outlines
      basement membranes of endothelia and smooth muscle cells of the vessel wall, but
      without differences between the four groups. No severe reactions were observed.
      CONCLUSIONS: The relative resistance of ITA to arteriosclerosis could be
      demonstrated in 227 ITA segments. Immunohistochemistry supports
      histomorphological findings. The influence of diabetes mellitus and irradiation
      remains irrelevant.

PMID- 15470606
TI  - Are men treated better than women? Outcome of male versus female patients after
      CABG using bilateral internal thoracic arteries.
AB  - BACKGROUND: Apart from smaller native coronary arteries a lower number of
      anastomoses and a lower ITA incidence have been suggested as being responsible
      for the increased mortality in female patients compared to males. The aim of this
      study was to clarify whether the outcome of females might be a consequence of a
      different regimen in anastomosis and ITA frequency. METHODS: We evaluated
      operative data and early outcome of 6906 patients with isolated CABG operated
      between 1/96 - 7/03 3064 out of 5381 males received bilateral ITA (BITA) vs. 750
      of 1525 females. Single ITA (SITA) was performed in 2126 males and 704 females.
      RESULTS: Demographic and operative data: average age for male patients was 64.0
      +/- 9.2 years, for females 68.5 +/- 8.6 years ( p < 0.05). The prevalence of
      diabetes mellitus was significantly higher in females (34.6 % vs. 27.4 %, p <
      0.01). Body mass index (BMI, 26.6 vs. 27.4 mean), incidence of main stem stenosis
      (23.0 % vs. 23.5 %), ejection fraction < 40 % (7.8 % vs. 10.1 %), urgent or
      emergent operations (13.1 % vs. 11.3 %) and number of performed anastomoses (3.2
      vs. 3.5 mean) showed no significant difference between males and females. Total
      ITA frequency did not differ (95.3 % vs. 96.5 %), but BITA frequency was
      significantly higher (56.9 % vs. 49.2 %, p < 0.01) in male patients. Overall 30
      day mortality was 2.8 % for males vs. 4.1 % ( p < 0.05) for females. Cardiac
      related mortality was significantly higher in female patients (2.6 % vs. 1.1 %, p
      < 0.01). Non-cardiac-related mortality did not differ significantly. Graft
      related mortality for males and females revealed 2.7 % in the BITA, 3.3 % in the
      SITA group and 6.9 % for patients without ITAs and reached statistical
      significance ( p < 0.01) for SITA or BITA vs. the no-ITA group, but not for BITA
      vs. SITA grafting. Nevertheless cardiac-related mortality in male and female
      patients without an ITA graft was more than two-fold higher compared to these
      with single ITAs and more than three-fold higher compared to those with BITA
      grafting. CONCLUSIONS: Female gender, frequently associated with diabetes
      mellitus, presents a predictor for increased mortality in CABG. A discrimination
      of women with respect to a restriction of ITA grafting could be confirmed only
      for bilateral ITAs. The superior results of bilateral ITA grafts are independent
      of gender.

PMID- 15470607
TI  - Effect of smoking status on mortality and morbidity following coronary artery
      bypass surgery.
AB  - BACKGROUND: We aimed to examine the effect of smoking on outcomes following
      coronary artery bypass grafting (CABG). METHODS: We retrospectively analysed 6
      367 consecutive patients who underwent CABG between April 1997 and March 2003.
      Logistic regression was used to risk adjust in-hospital outcomes, while Cox
      proportional hazards analysis was used to risk adjust Kaplan-Meier survival
      curves. Outcomes were adjusted for variables suggested by the American Heart
      Association and American College of Cardiology. RESULTS: 947 (14.9 %) patients
      were current smokers (smoking within 1 month of surgery), while 3857 (60.6 %)
      were ex-smokers and 1 563 (24.5 %) were non-smokers. After adjusting for
      differences in case-mix, current smokers were more likely to develop chest
      infections ( p < 0.001), atelectasis ( p < 0.001), and require ventilation longer
      than 48 hours ( p = 0.003). Current smokers were also more likely to stay in
      intensive care for more than 3 days ( p < 0.001). Ex-smokers were not associated
      with excess mortality ( p = 0.11), while current smokers had significantly
      increased mortality during follow-up ( p = 0.029). CONCLUSIONS: Patients should
      be encouraged to stop smoking to maximise the long-term benefits of CABG.

PMID- 15470608
TI  - Pre- and postoperative assessment of left ventricular function by magnetic
      resonance imaging and 2-D-echocardiography in patients undergoing left
      ventricular aneurysmectomy.
AB  - BACKGROUND: Left ventricular (LV) aneurysms may complicate myocardial
      infarctions. Reliable quantification of LV functional parameters is mandatory to
      predict clinical outcome in patients undergoing LV aneurysmectomy. We compared
      global LV function measured by magnetic resonance (MR) and 2-D-echocardiography
      in patients before and after aneurysmectomy. METHODS: 31 patients (23 male), mean
      age 64 (range 35 - 85) years with an LV aneurysm (25/31 anterior MI, 5/31
      inferior MI, 1/31 both) were enrolled. MR and echocardiography were performed
      directly before and 3 - 65 (median 8) days after surgery. MR studies were
      performed on a 1.5 Tesla scanner. End-diastolic and end-systolic volumes and
      diameters (EDV/ESV, EDD/ESD), ejection fraction (EF) and stroke volume (SV) were
      determined. Echocardiography was performed to determine EF, EDD and ESD. NYHA
      class was assessed before and 3 months after surgery. RESULTS: After
      aneurysmectomy MR analysis showed a decrease in EDV (255 +/- 68 ml to 202 +/- 59
      ml) ( p < 0.001) and ESV (186 +/- 71 ml to 134 +/- 53 ml; p < 0.001); EF
      increased (28 +/- 10 % to 35 +/- 12 %; p < 0.001); EDD/ESD decreased ( p < 0.01).
      Compared to echocardiography, a low correlation was found in EF before/after
      surgery r = 0.76/r = 0.69 and ESD r = 0.43/r = 0.60, respectively. In EDD a good
      correlation was found before surgery (r = 0.81), and a lower correlation after
      surgery (r = 0.72). NYHA class improved from 3.0 +/- 0.5 before to 1.8 +/- 0.8
      after operation ( p < 0.001). CONCLUSION: Resection of an LV aneurysm results in
      a mean improvement of 25 % in LV function, and improved clinical outcome. In
      asymmetric ventricles with aneurysms MR proved to be superior as a sensitive and
      non-invasive tool compared to conventional 2-D-echocardiography.

PMID- 15470609
TI  - Additional pulmonary blood flow has no adverse effect on outcome after TCPC.
AB  - BACKGROUND: Use of additional sources of pulmonary blood flow (APBF) with
      bidirectional cavopulmonary anastomosis (BDG) and total cavopulmonary connection
      (TCPC) remains controversial. We have therefore assessed the effects of APBF on
      BDG and TCPC outcome. METHODS: From 1996 to 2000, 106 patients underwent BDG,
      either isolated (group 1, n = 54), or with APBF via pulmonary artery (PA) (group
      2, n = 30), or Blalock-Taussig shunt (BTS) (group 3, n = 22) with 28 patients
      completed by TCPC. RESULTS: After BDG low output syndrome was more frequent in
      group 2 and less in 3 ( p = 0.01), whereas superior cava syndrome was again more
      common in group 2 and less in groups 1 and 3 ( p < 0.05) than expected. Mortality
      and complications were similar after TCPC in all groups. Oxygen saturation (SaO
      (2)) was lower without than with APBF ( p < 0.002) after BDG and in group 3 than
      in group 2 after TCPC ( p < 0.05). Repeated measures ANOVA showed no effect of
      APBF on SaO (2), PA pressures, fractional shortening, end-diastolic pressure and
      AV-valve function. CONCLUSIONS: Early after BDG, APBF via PA presents different
      difficulties than APBF via BTS. However, BDG and TCPC outcomes are not affected
      by the presence or absence of APBF.

PMID- 15470610
TI  - Determination of the coronary flow reserve of the LAD in patients with HOCM using
      the intracoronary Doppler catheter.
AB  - OBJECTIVE: Hypertrophic obstructive cardiomyopathy (HOCM) is still a serious
      problem that is characterized by an increasing hypertrophy of the cardiac muscle.
      The aim of this study was to investigate the hypothesis whether in HOCM the
      coronary flow reserve in the left anterior descending artery (LAD) is influenced
      by pharmacologic stimulation or stimulation using a pacemaker. PATIENTS AND
      METHODS: The study was carried out in 15 patients (6 male, 9 female) with the
      typical echocardiographic signs of HOCM without coronary artery disease. Using an
      intracoronary Doppler catheter the average peak velocity and the absolute
      coronary flow reserve were determined in the proximal, medial and distal part of
      the LAD under influence of Papaverine, Substance P and under pacemaker
      stimulation. The coronary square plane was calculated angiographically under the
      influence of Substance P. Moreover, the retrograde flow was studied and the
      coherence between the increase of the coronary square plane and the coronary flow
      reserve were investigated. For statistical analysis the mean value, the standard
      error of the mean, Spearman's correlation coefficient and the t-test were
      calculated. RESULTS: Under pharmacologic stimulation higher values in the average
      peak velocity were observed compared to pacemaker stimulation. A retrograde flow
      was observed in 8 out of 10 patients. The coronary flow reserve was higher under
      pharmacologic influence than under pacemaker stimulation. A coherence between the
      increase of the coronary square plane and the coronary flow reserve was not
      found. CONCLUSIONS: So far, from the published data concerning the
      characteristics of coronary flow in HOCM patients, only the retrograde flow was
      reproducible in our patient group. However, a decrease of the coronary flow
      reserve compared to a healthy control group of the literature could not be
      observed. Nevertheless ischemia in the subordinate vessels and on the base of
      microcirculation cannot be excluded.

PMID- 15470611
TI  - Results of surgical treatment for non-small cell lung cancer of 20 mm or less in
      diameter.
AB  - BACKGROUND: Surgical efficacy is still unsatisfactory for small lung cancer;
      accordingly, minimal resection has recently been the focus of increased study.
      The objective of the current study was to evaluate the factors associated with
      small lung cancer, and to determine whether such factors are reliable predictors
      of long-term survival. METHODS: We retrospectively investigated 130 patients with
      histologically confirmed non-small cell carcinoma, whose treatments were
      primarily surgical, with no chemotherapy or radiotherapy prior to surgery. All
      tumors were located peripherally and were less than 20 mm in diameter. Follow-up
      was performed for five-year and eight-year survivors and multivariate analysis
      with Cox's proportional hazards regression model was performed. RESULTS: Of all
      130 patients, the 5-year survival rate among patients with tumors less than 15 mm
      was 82.5 %, vs. 57.4 % of patients with tumors with a diameter of 16 - 20 mm. The
      5-year survival rate of patients who were node negative was 73.9 % while it was
      28.5 % for node-positive patients. Status of nodal invasion was also
      significantly associated with survival in small-size tumors ( p < 0.0001).
      Furthermore, the 5-year survival rate among patients with pleural involvement was
      55 % vs. 83.8 % for patients without pleural involvement. Using multivariate Cox
      analysis, lymph node involvement ( p = 0.0004), size ( p = 0.0475), and pleural
      invasion ( p = 0.0482) were found to be independent prognostic factors in cases
      of tumors 20 mm or less in diameter. CONCLUSIONS: The results of this study at
      least demonstrate that the optimal therapy for patients with nodal involvement or
      patients with tumors of 16 - 20 mm must be carefully determined even in cases of
      small lung cancer.

PMID- 15470612
TI  - Late postpneumonectomy bronchopleural fistula.
AB  - OBJECTIVE: The incidence of late postpneumonectomy bronchopleural fistula (PBPF)
      is very small after the 3rd postoperative week due to the existence of
      fibrothorax providing an effective natural protection against fistula formation.
      However, the development of late PBPF is a serious complication characterized by
      high morbidity and mortality. We present our modest experience in treating 11
      patients with late PBPF using the transsternal transpericardial approach.
      MATERIAL: Between 1996 and 1999, 11 male patients with a mean age of 61 years
      were treated in our department for late PBPF (diameter > 5 mm). The interval
      between pneumonectomy and fistula creation ranged from 1 to 10 years. The initial
      operation was right pneumonectomy in all cases due to lung cancer. pTNM stage was
      either II or IIIA. Bronchoscopically no recurrence was observed and empyema was
      present in all cases. RESULTS: The initial treatment consisted of tube
      thoracostomy. We proceeded to direct bronchial stump repair transpericardially
      with omental flap coverage and finally open window thoracostomy. Neither deaths
      nor major complications occurred perioperatively. The ICU and hospital stay
      ranged from 5 to 10 and 30 to 45 days, respectively. During a follow-up of 10 to
      28 months no recurrence was observed. CONCLUSIONS: 1. The management of late
      large PBPF can be only surgical. 2. Fibrothorax and empyema makes the approach
      through thoracotomy impossible and dangerous for dissection and repair. 3.
      Bronchial stump repair through the transpericardial approach by median sternotomy
      is very effective in late PBPF cases where the patient's general condition is
      good, allowing a major intervention.

PMID- 15470613
TI  - Cystic tumor in the left atrium: an unusual aspect of a myxoma.
AB  - Most cardiac tumors are benign, whereas up to 50 % of the diagnosed cases are
      histologically myxomas. The common clinical signs are rhythm disturbances,
      myocardial ischemia, pulmonary edema, syncope and cardiac arrest. They do
      normally lead to the diagnostic hypothesis of an intracardiac mass. The primary
      modality for imaging is echocardiography which usually confirms the suspected
      diagnosis. But in rare cases there are masses which cannot be exactly identified
      by this technique. Here we present a patient with an atypical echocardiography of
      an unusual intracardiac tumor.

PMID- 15470615
TI  - Cardiac surgery in Germany during 2003: a report by the German Society for
      Thoracic and Cardiovascular Surgery.

PMID- 15470614
TI  - A murine model of ischemic cardiomyopathy induced by repetitive ischemia and
      reperfusion.
AB  - BACKGROUND: Repetitive brief myocardial ischemia has been implicated in the
      pathogenesis of the ventricular dysfunction associated with ischemic
      cardiomyopathy and myocardial hibernation. In this study we examine the effects
      of repetitive ischemia and reperfusion (I/R) on murine myocardium. METHODS:
      C57/BL6 mice underwent daily 15 min left anterior descending coronary occlusions
      followed by reperfusion. After 3, 5, 7, 14, 21 and 28 days, echocardiographic
      studies were performed, and hearts of I/R and sham-operated animals were
      processed for histological examination. RESULTS: Histological studies showed no
      evidence of myocardial necrosis in the ischemic region. Quantitative assessment
      of collagen revealed a marked persistent interstitial deposition of collagen
      after seven days I/R in the anterior left ventricular wall (sham 4.6 +/- 2.0 %,
      I/R 21.5 +/- 6.5 %, p < 0.05). Echocardiographic studies showed persistent
      regional anterior wall dysfunction in I/R animals. Histological evaluation showed
      absence of neovessel formation. After discontinuation of the I/R protocol,
      fibrosis and regional ventricular dysfunction decreased within 60 days.
      CONCLUSIONS: Repetitive brief murine myocardial I/R induces reversible fibrotic
      remodeling and ventricular dysfunction, without myocardial infarction and
      necrosis, and may play a role in the pathogenesis of ischemic cardiomyopathy and
      myocardial hibernation.

PMID- 15470616
TI  - [Issues about on-line manuscript submission and evaluation].

PMID- 15470617
TI  - [Barium sulphate allergy (case report)].
AB  - Barium sulphate is a commonly used agent in the radiographic studies of the
      gastrointestinal tract and has been regarded as a safe contrast medium. Barium
      sulphate allergy is very rare. We present a case of barium sulphate allergy which
      occurred during an upper gastrointestinal study in a 24-year-old woman.

PMID- 15470618
TI  - [Double inversion recovery sequence in temporal lobe epilepsy: preliminary
      results].
AB  - PURPOSE: DIR (double inversion recovery) is a sequence with the hybrid contrast
      of both FLAIR and STIR sequences, produced by the application of double inversion
      recovery pulse. It has been suggested that DIR provides high sensitivity to
      lesions with low T2 contrast. The purpose of this study was to test the
      hypothesis that DIR sequence is superior to conventional sequences in the
      identification of mesial temporal sclerosis and other temporal lobe lesions in
      patients with temporal lobe epilepsy. MATERIALS AND METHODS: Thirty-three
      subjects with a prediagnosis of temporal lobe epilepsy and ten healthy control
      subjects with no abnormality on magnetic resonance imaging studies have been
      studied with DIR, FLAIR and T2W sequences. Coronal images through temporal lobes
      and hippocampus were acquired. Qualitatively, overall sensitivity to the presence
      of lesions, hippocampal lesion detectability, temporal horn dilatation and
      artifacts were evaluated in temporal lobe epilepsy cases and quantitatively,
      hippocampal and white matter signal-to-noise ratio as well as hippocampus-white
      matter contrast-to-noise ratio were calculated in the healthy subjects.
      Subjective scores were graded on a scale of 3 or 4 points. RESULTS: Signal-to
      noise ratio scores were higher on T2W sequence, however contrast-to-noise ratio
      scores were higher on DIR sequence compared to the other two sequences. Imaging
      findings were compatible with mesial temporal sclerosis in seven patients,
      tumoral mass in two, and chronic infarct in four. DIR sequence was less sensitive
      to hippocampal atrophy than the other two sequences because of cerebrospinal
      fluid artifacts. Overall sensitivity to the presence of lesions and hippocampal
      lesion detectability scores, although similar among three sequences, were highest
      with DIR sequence. However, lesion sensitivity scores were highest for lesions
      compatible with mesial temporal sclerosis and for solid masses and lowest for
      cystic lesions on DIR sequence. CONCLUSION: Despite the presence of artifacts,
      DIR is a sequence providing high sensitivity to mesial temporal sclerosis like
      lesions at hippocampus. DIR might be useful as an additional sequence when the
      other conventional sequences reveal a suspicious lesion with no accompanying
      hippocampal atrophy.

PMID- 15470619
TI  - [The role of three dimensional MR myelography in lumbar discogenic disease].
AB  - PURPOSE: To evaluate the role of the three dimensional (3D) MR myelography (MRM)
      in the diagnosis of the lumbar discogenic disease compared with conventional MR
      imaging. MATERIALS AND METHODS: Fifty consecutive patients with clinical symptoms
      of lumbar disc herniation were enrolled for the study. Conventional MR imaging
      and coronal 3D MRM were performed on a 1.5 T MR system. At each disc space level,
      the presence and the location of disc herniation and nerve root compression were
      evaluated. Note was also made if MRM had additional contribution to the
      determination of most significant level in the cases of multilevel disc disease
      and lumbar spinal stenosis. RESULTS: Disc herniation was found in 60 disc space
      levels on conventional MR imaging and in 54 disc space levels on 3D-MRM imaging.
      As regards to disc herniation, the sensitivity, specificity, and accuracy of 3D
      MRM was 90%, 100%, and 96%, respectively. Nerve root compression was seen in 91
      levels on conventional MR images, as opposed to 98 on 3D-MRM. Regarding nerve
      root compression, the sensitivity, specificity, and accuracy of 3D-MRM was 100%,
      97%, and 98%, respectively. In all of 13 patients with multilevel disc disease
      and lumbar spinal stenosis, 3D-MRM had additional contribution. CONCLUSION: Scan
      time of 3D-MRM is short. It can be easily added to routine lumbar MR imaging. It
      may be a valuable modality in the diagnosis of the lumbar discogenic disease. The
      presence of false-negative and false-positive examinations necessitates caution
      in interpreting 3D-MRM images. 3D MRM technique may be useful in selected cases
      such as patients with multilevel disc abnormalities or lumbar spinal stenosis
      where it allows a rapid and easy appreciation of the level most likely to account
      for the pathology.

PMID- 15470620
TI  - [Spontaneous trans-sphenoidal encephalocele presenting with nontraumatic
      cerebrospinal fluid rhinorrhea (case report)].
AB  - Encephaloceles are uncommon and can arise from congenital, traumatic, or
      spontaneous origins. Approximately 80% of all cerebrospinal fluid rhinorrheas are
      caused by head injuries. Spontaneous or nontraumatic encephaloceles or
      cerebrospinal fluid leaks have been the least common in most series, accounting
      for only 3% to 5% of all cerebrospinal fluid leaks. There is a high incidence of
      meningitis and brain abscess. Thus, early diagnosis is very important. We present
      an adult patient with uncomplicated nontraumatic cerebrospinal fluid rhinorrhea
      that was caused by spontaneous trans-sphenoidal encephalocele.

PMID- 15470621
TI  - [Adrenoleukodystrophy: single voxel MR spectroscopy findings (case report)].
AB  - Adrenoleukodystrophy is a rare genetic disorder. Histopathological features of
      this disorder include demyelination and axonal loss in white matter. We describe
      a six-year-old boy with significantly decreased N-acetyl-aspartate (NAA)/Creatin
      (Cr), increased Choline (Cho)/Cr and Myo-inositol (MI)/Cr in parieto-occipital
      white matter by MR spectroscopy. In contrast to the normal appearance of frontal
      white matter on MR imaging, increased Cho/Cr and MI/Cr ratios were detected on MR
      spectroscopy. These changes in involved areas could be an indication of
      neuroaxonal loss, demyelination and gliosis.

PMID- 15470622
TI  - [Multidetector computed tomography in the diagnosis of parathyroid adenomas:
      contribution of contrast enhancement pattern to diagnosis].
AB  - PURPOSE: Contrast enhancement patterns of parathyroid adenomas in the arterial
      and venous phases were evaluated with multidetector computed tomography and
      specificity of the method to characterize the lesions was investigated. MATERIALS
      AND METHODS: Arterial and venous enhancement patterns of parathyroid adenomas
      were evaluated retrospectively with multidetector computed tomography in 12
      patients. All adenomas were removed surgically and the diagnosis was confirmed
      histopathologically. An area from the mandibular angle to the aortic arch was
      scanned with 1.5 mm section thickness in the arterial phase (20 seconds delay
      time) and venous phase (70 seconds delay time) after bolus injection of 50 ml of
      iodinated contrast media. Arterial and venous contrast enhancement of parathyroid
      adenomas was evaluated in the axial and coronal reformat images. RESULTS: Ten
      (83.3%) of 12 parathyroid adenomas showed a heterogeneous enhancement with a
      hypodense small central area in the arterial phase and a homogeneous enhancement
      in the venous phase. However, two small lesions, four and five mm in diameter
      respectively, showed homogeneous contrast enhancement in the arterial phase
      unlike the larger lesions which displayed a hypodense center in this phase.
      CONCLUSION: Dynamic scanning with multidetector computed tomography after
      contrast administration may be helpful in characterizing parathyroid adenomas.

PMID- 15470623
TI  - [Mediastinal hemangioma (case report)].
AB  - We present radiographic and computed tomographic findings of a mediastinal
      hemangioma, a very rare benign vascular tumor that comprises less than 0.5% of
      all mediastinal masses. Posteroanterior chest film showed a homogeneous opacity
      in the left upper zone that was contiguous with the mediastinum. Computed
      tomography demonstrated a mediastinal mass with inhomogeneous contrast
      enhancement and a small calcification.

PMID- 15470624
TI  - [Mammography-related pain and anxiety].
AB  - PURPOSE: To investigate whether informing patients about mammographic compression
      changed the anxiety and pain that they experience during mammography. MATERIALS
      AND METHODS: Five hundred and one patients were enrolled in the study. Two
      hundred and fifty seven (51.3%) were informed before the procedure by written
      forms explaining the necessity of compression. The remaining 244 (48.7%) didn't
      get any pre-procedural information. All participants completed demographic form
      and Spielberger's State Anxiety Inventory while they were waiting for
      mammography. They marked the level of pain due to compression on a 100-mm visual
      analog scale (VAS) after the procedure. Chi square, Pearson's correlation and
      Student's t tests were used for statistical analyses. RESULTS: We didn't find any
      significant difference between the anxiety scores of the informed (41.4+/-7.9)
      and uninformed (40.9+/-7.7) women, but the pain level was significantly lower in
      the informed group (16.5+/-22.4) than in the uninformed group (24.5+/-28.1).
      There was no statistically significant relationship between the anxiety and pain
      levels. Women who had recently felt tense and nervous or had a fear of breast
      cancer diagnosis had higher anxiety levels. CONCLUSION: Our data shows that
      informing patients about examination decreases the level of pain due to
      mammographic compression, but does not alter the anxiety level. The main cause of
      anxiety appears to be the fear of a malignant diagnosis. Any intervention to
      decrease this fear may increase the compliance rates for screening mammography.

PMID- 15470625
TI  - [Diagnostic efficiency of multislice computed tomography colonography in the
      detection of colorectal tumors: comparison with conventional colonography].
AB  - PURPOSE: To evaluate the diagnostic efficiency of multislice CT colonography in
      the detection of colorectal tumors by comparing it with conventional colonography
      in patients with high risk of colorectal cancer. MATERIALS AND METHODS: Thirty
      seven patients who had undergone conventional colonoscopy because of a suspicion
      of colorectal cancer were scanned with a four-detector multislice CT scanner with
      4 x 1 mm detector collimation, 120 kV, 0.5 sec gantry rotation and 120 mAs scan
      parameters. Multiplanar reformatted images, virtual colonography and virtual
      colonoscopy images were compared with conventional colonoscopy. With conventional
      colonoscopy taken as the reference standard, the results were calculated with 95%
      confidence interval technique. RESULTS: Seventeen of the 23 polyps detected in
      conventional colonoscopy were identified correctly with multislice CT. Nine of 11
      lesions with a diameter of 10 mm or greater (81%), three of four lesions with a
      diameter of 6-9 mm (75%), and five of eight lesions with a diameter of 1-5 mm
      (62%) were correctly identified with multislice CT. CONCLUSION: Multislice CT
      colonography is a good alternative to other colorectal screening tests because it
      has high sensitivity for polyps 10 mm or larger in diameter, is relatively safe
      and minimally invasive.

PMID- 15470626
TI  - [Effect of propranolol on renal hemodynamics in patients with cirrhosis:
      assessment with Doppler US].
AB  - PURPOSE: To determine the renal resistive index profile in cirrhotic patients
      before and after propranolol treatment and assess the effects of propranolol on
      renal hemodynamics. MATERIALS AND METHODS: Thirty-six patients with cirrhosis and
      ascites (decompensated group), 39 patients with cirrhosis but no ascites
      (compensated group) and 25 patients with normal renal and hepatic functions
      (control group) were studied. All had normal blood urea nitrogen and serum
      creatinine levels. The renal resistive index was calculated in all patients
      before and after oral propranolol treatment. RESULTS: Resistive index was
      significantly higher in the decompensated group (p<0.05) than in other groups.
      After propranolol treatment, resistive indices decreased in the compensated
      patients (p<0.05) but increased in the decompensated group (p<0.05). There was a
      slight but statistically insignificant increase in the control group. CONCLUSION:
      In patients with cirrhosis renal failure is a significant risk factor for liver
      transplantation. In these patients, Doppler sonography provides early detection
      of renal dysfunction even before renal function tests are abnormal. Doppler
      sonography is a useful noninvasive method to evaluate the effects of drugs on
      renal hemodynamics.

PMID- 15470628
TI  - [Thoracopancreatic fistula: imaging findings (case report)].
AB  - Thoracopancreatic fistula is a rare complication of acute and chronic
      pancreatitis caused by an inflammatory or traumatic injury to the main pancreatic
      duct or side branches. Rupture of the duct into the pleura, pericardium, and
      mediastinum may present as a pancreaticopleural fistula, mediastinal pseudocyst,
      pancreaticobronchial or pancreticopericardial fistula. We present the imaging
      findings in a rare case of thoracopancreatic fistula caused by recurrent
      pancreatitis.

PMID- 15470627
TI  - [Plasental chorioangioma (case report)].
AB  - Placental chorioangioma is the most common benign tumor of placenta, encountered
      in approximately 1% of all pregnancies. Clinical manifestations are rare and
      usually associated with tumors greater than 5 cm in diameter. They include
      polyhydramnios, congestive heart failure, anemia, prematurity, growth
      retardation, and intrauterine fetal death. We report a case of chorioangioma of
      the placenta in which ultrasonography and Doppler ultrasonography findings were
      useful in establishing the prenatal diagnosis.

PMID- 15470629
TI  - [Subcapsular fatty infiltration of the liver in peritoneal dialysis patients
      treated with intraperitoneal insulin: US and CT features (case report)].
AB  - In recent years a characteristic subcapsular and periligamentous fatty
      infiltration of the liver has been reported in diabetic patients on
      intraperitoneal insulin treatment by continuous ambulatory peritoneal dialysis.
      The finding is unique to these patients on continuous ambulatory peritoneal
      dialysis and has not been defined in diabetics using subcutaneous insulin. We
      present characteristic US and CT findings in two such patients with focal
      subcapsular fatty infiltration of the liver.

PMID- 15470630
TI  - [Ganglion cysts of the knee originating from tendons and ligaments].
AB  - PURPOSE: To investigate the clinical features and MR imaging findings of the
      ganglion cysts arising from the tendons and ligaments of the knee. MATERIALS AND
      METHODS: One thousand six hundred and twenty knee MR examinations that had been
      performed in a three-year period were evaluated retrospectively for the presence
      of ganglion cysts originating from tendons or ligaments. Clinical findings and
      MRI features of the lesions were noted. RESULTS: Twenty-three patients had a
      ganglion cyst originating from a tendon or a ganglion, with an incidence of 1.4%.
      Six lesions were associated with the anterior cruciate ligament, six with the
      posterior cruciate ligament, six with the medial collateral ligament, two with
      the lateral collateral ligament, two with the transverse ligament, and one with
      the patellar tendon. The most common clinical finding was knee pain. There were
      swelling at the medial side of the knee in two patients, swelling at the lateral
      side of the knee in one patient and swelling in the popliteal region in one
      patient. CONCLUSION: MR appearance of ganglion cysts arising from the tendons and
      ligaments of the knee is characteristic. Meniscal cysts, pigmented villonodular
      synovitis, and synovial hemangioma should be considered in the differential
      diagnosis.

PMID- 15470631
TI  - [Endovascular treatment of vertebral artery origin stenosis in high risk
      patients].
AB  - PURPOSE: Atherosclerotic stenosis of the vertebrobasilar system most commonly
      occurs at the vertebral artery origin. Stenting of these stenotic lesions in
      combination with antithrombotics with or without anticoagulants is a safe and
      effective treatment method. The purpose of this study is to present the results
      of vertebral artery origin stenting in 14 high-risk patients. MATERIALS AND
      METHODS: Significant vertebral artery origin stenosis was treated with primary
      stenting in 14 patients, aged between 58 and 74 years (mean, 66+/-5.3 years).
      Eleven patients were male, and three were female. Vertebral artery stenosis was
      detected in eight patients prior to coronary artery surgery, and in six patients
      after a posterior system stroke or during evaluation of a vertebrobasilar
      insufficiency. All stenosis were successfully treated with stent placement.
      Except one patient who had a left posterior cerebral artery infarction, all
      patients had an uneventful procedure without any complication. Third-month and
      sixth-month clinical and color Doppler follow-up examinations were available in
      ten patients, and 12th-month control angiography performed in three patients did
      not show stent restenosis. None of the patients had new neurologic deficit during
      the follow-up. CONCLUSION: Vertebral artery origin stenoses are one of the most
      common causes of vertebrobasilar stroke. In the presence of concomitant cerebral
      artery stenosis or systemic disorders, patients are under high risk even if they
      are on medical therapy. Primary stenting combined with medical treatment is a
      safe and effective treatment modality.

PMID- 15470632
TI  - Yves Delage (1854-1920) as a forerunner of modern nuclear transfer experiments.
AB  - It is generally considered that animal cloning by nuclear transfer originated in
      proposals made by Hans Spemann (1936), following his experiments on delayed
      nucleation in the newt egg, which were preceded by similar attempts using the sea
      urchin egg (Loeb, 1894). Briggs and King (1952) were the first to succeed in
      transplanting blastula and gastrula nuclei into the enucleated frog egg and in
      obtaining a significant number of normal tadpoles by means of this technique. We
      present evidence that much earlier (1895) Yves Delage (1854-1920), a French
      biologist, had clearly formulated the same experimental project of nuclear
      transfer, as a means to test Weismann's theory of cell differentiation during
      embryonic development. This was also Spemann's motivation. Both Delage and
      Spemann were aware of Loeb's experiments (1894), in which delayed nucleation in
      the sea-urchin egg was found to result in twin larvae. It is difficult to decide
      whether Delage's project was influenced by Loeb's findings. On the other hand, it
      seems that Spemann was not aware of Delage's proposal, since he did not express
      his own ideas on extended nuclear transfer before 1936. Finally, neither Delage
      nor Spemann imagined that nuclear transfer could be a means of obtaining groups
      of genetically identical animals (reproductive cloning).

PMID- 15470633
TI  - Additional enhancer copies, with intact cdx binding sites, anteriorize Hoxa
      7/lacZ expression in mouse embryos: evidence in keeping with an instructional cdx
      gradient.
AB  - Expression of a Hoxa-7/lacZ reporter construct in transgenic mouse embryos is
      shifted anteriorly when the upstream enhancer is multimerized. The shift occurs
      in spinal ganglia, neurectoderm and in both paraxial and lateral plate mesoderms.
      Much of the multimer effect is inhibited by destruction of a single caudal (cdx)
      binding motif in the additional copies of the enhancer. These observations are in
      agreement with earlier enhancer multimerization analyses made for Hoxb-8 (Charite
      et al., 1998). Our findings therefore provide further evidence that the anterior
      limit of a Hox gene's expression domain is normally dependent upon and is
      determined by, the dosage of transcription factor(s) which bind to its enhancer
      element(s) and that these factors may be, or must include, the cdx proteins. We
      consider these findings in terms of both instructional (morphogen-like) gradient
      and timing models for the establishment of Hox gene expression domains. Enhancer
      multimerization results in an earlier onset of Hoxa-7/lacZ activity in the
      embryo. In neurectoderm at 8.7 days and in mesoderm at 10.5 days, the anterior
      boundaries of expression are located posterior to those seen at some earlier
      stages of development. We discuss how these findings are in keeping with a model
      where Hox expression boundaries become set along instructional cdx gradients,
      formed by cdx decay in cells moving away from the primitive streak region.

PMID- 15470634
TI  - Pbx genes are required in Xenopus lens development.
AB  - Development of the vertebrate eye is dependent on multiple tissue interactions
      and distinct sets of transcription factors and signalling molecules. The latter
      are thought to be FGF8 and BMP4, proteins secreted from the neural plate to
      induce lens formation in the overlying ectoderm. Here we show that the Pbx
      transcription factor plays a crucial role in this process, as it is required for
      FGF8 expression in the neural plate and is thus part of the complex hierarchy of
      genes involved in lens induction.

PMID- 15470635
TI  - X-chromosome inactivation in differentiating mouse embryonic stem cells carrying
      X-linked GFP and lacZ transgenes.
AB  - Three new female ES cell lines (GLM1, GLP1 and GLP2) were established from mouse
      embryos carrying GFP (green fluorescent protein) and HMG-lacZ transgenes on one
      of two X chromosomes in cis. Using these cell lines, we studied the temporal
      relationships among three events relevant to X-chromosome inactivation:
      replication asynchrony of the X chromosome, and quenching of GFP fluorescence and
      beta-galactosidase (beta-gal) activity, during cell differentiation induced by
      embryoid body (EB) formation and retinoic acid (RA) treatment. In embryoid bodies
      adhering to the bottom of culture dishes, GFP-negative cells appeared first in
      the peripheral outgrowths 4 days after the initiation of EB formation, followed
      about 24 hours later by the appearance of cells negative for beta-gal and those
      having a single allocyclic X chromosome. Although the frequency of cells with an
      allocyclic X chromosome could reach 80% in adherent embryoid bodies, it tended to
      remain low and variable in embryoid bodies maintained in suspension. In spite of
      apparently parallel extinction of GFP and lacZ in embryoid bodies, their
      concurrent occurrence did not always characterize RA-induced differentiation.
      Moreover, an allocyclic X chromosome was identified in not more than 20 percent
      of informative metaphase cells up to 10 days after initiation of RA treatment.
      These findings suggest that RA-induced differentiation of female ES cells does
      not always accompany X-inactivation.

PMID- 15470636
TI  - Effects of FGF9 on embryonic Sertoli cell proliferation and testicular cord
      formation in the mouse.
AB  - Proliferation and cord formation by embryonic Sertoli cells are pivotal events
      involved in testis morphogenesis. A number of growth factors have been implicated
      in mediating these events. However, the exact level of involvement and importance
      of each as yet remains elusive. We have adopted an in vitro approach to assess
      developing mouse Sertoli cells, whereby they are cultured in the presence or
      absence of fibroblast growth factor (FGF9) and/or extracellular matrix (ECM) gel,
      since previous studies have shown that ECM gel aids Sertoli cell differentiation.
      The present findings corroborate this effect, but in addition demonstrate that in
      the presence of FGF9 (10 ng/ml), cells undergo greater proliferation than those
      cultured on gel alone. They also display a differentiated epithelial phenotype,
      with appositional contact of cell membranes in cord-like aggregations. In
      addition we have shown that cultured Sertoli cells generally express a smaller
      truncated, nuclear form of the FGFr3, although in the presence of FGF9 and
      absence of gel, the larger, cytoplasmic form of the receptor is also expressed.
      Immunolocalisation of FGFr3 in Sertoli cells of whole testes revealed a temporal
      expression pattern profile, with high levels being abundant in the embryonic
      testicular cords and at puberty, but an absence in adult Sertoli cells. Our
      findings suggest that FGF9 plays an important role in proliferation and
      organisation of embryonic Sertoli cells during testis morphogenesis.

PMID- 15470637
TI  - Expression and activity of osteoblast-targeted Cre recombinase transgenes in
      murine skeletal tissues.
AB  - The Cre/loxP recombination system can be used to circumvent many of the
      limitations of generalized gene ablation in mice. Here we present the development
      and characterization of transgenic mice in which Cre recombinase has been
      targeted to cells of the osteoblast lineage with 2.3 kb (Col 2.3-Cre) and 3.6 kb
      (Col 3.6-Cre) fragments of the rat Col1a1 promoter. Cre mRNA was detected in
      calvaria and long bone of adult Col 2.3-Cre and Col 3.6-Cre mice, as well as in
      tendon and skin of Col 3.6-Cre mice. To obtain a historical marking of the
      temporal and spatial pattern of Cre-mediated gene rearrangement, Col-Cre mice
      were bred with ROSA26 (R26R) mice in which Cre-mediated excision of a floxed
      cassette results in LacZ expression. In Col 2.3-Cre;R26R and Col 3.6-Cre;R26R
      progeny, calvarial and long bone osteoblasts showed intense beta-gal staining at
      embryonic day 18 and postnatal day 5. The spatial pattern of beta-gal staining
      was more restricted in bone and in bone marrow stromal cultures established from
      Col 2.3-Cre;R26R mice. Similar differences in the spatial patterns of expression
      were seen in transgenic bone carrying Col1a1-GFP visual reporters. Our data
      suggest that Col 2.3-Cre and Col 3.6-Cre transgenic mice may be useful for
      conditional gene targeting in vivo or for obtaining osteoblast populations for in
      vitro culture in which a gene of interest has been inactivated.

PMID- 15470638
TI  - Differences in maternal supply and early development of closely related nematode
      species.
AB  - Comparative analyses revealed considerable differences in embryonic pattern
      formation and cell-specification between Caenorhabditis elegans and Acrobeloides
      nanus, members of two neighboring nematode clades. While C.elegans develops very
      rapidly, A. nanus needs 4-5 times as long. To investigate whether differences
      during early embryogenesis could be related to developmental tempo, we studied
      three more slowly developing representatives of the genus Rhabditis, thus close
      relatives of C.elegans. Besides differences in body size and mode of
      reproduction, they differ from C.elegans in the order of cleavages, germline
      behavior and requirement for early zygotic transcription, showing evident
      similarities to A. nanus. The distinct variations in cell-cycle rhythms and
      arrest after inhibition of transcription appear to reflect a species-specific
      interplay in the timing between exhausting maternal supplies and making available
      newly transcribed gene products. Looking for the reversal of cleavage polarity in
      the germline present in C.elegans but not in A. nanus, two of the studied species
      express this distinct feature only in a later cell generation. We found that a
      C.elegans mutant in the mes-1 gene shows a similar deviation. Concerning
      specification of the gut cell lineage and the potential to compensate for lost
      cells, the three tested Rhabditis species behave less regulatively, like
      C.elegans; in contrast to A. nanus, the gut precursor EMS requires an inductive
      signal from the germline cell P2 and an experimentally eliminated EMS cell is not
      replaced by a neighboring blastomere. In conclusion, embryogenesis of the
      examined Rhabditis species includes features of both the fast-developing C.
      elegans and the slow-developing A. nanus.

PMID- 15470639
TI  - Development of the dendrobatid frog Colostethus machalilla.
AB  - To provide a developmental correlate with other frogs, we prepared a normal table
      of development for the dendrobatid, Colostethus machalilla and analyzed the
      morphology of its early development. This frog reproduces in captivity and
      deposits moderately sized eggs (1.6 mm in diameter) in terrestrial nests. The
      father guards the embryos until tadpole hatching. We divided development until
      hatching into 25 stages and implemented methods for in vitro culture of the
      embryos. The external and internal morphology of embryos were evaluated by
      observations in whole mount and in sections. Neural, notochord and somite
      specific antibodies were used to analyze gene expression patterns by
      immunostaining of embryos. Embryonic development of C. machalilla is slow and
      deviates from Xenopus laevis. In C. machalilla the elongation of the notochord,
      neural plate and somite formation occur after blastopore closure, possibly due to
      a delay in the dorsal convergence and extension movements. The gastrula of C.
      machalilla also deviates from X. laevis. The archenteron remains small until
      blastopore closure, where small cells accumulate at the blastopore lips.
      Simultaneously, the blastocoel roof thins until it becomes a monolayer of cells.
      Although C. machalilla does not form an embryonic disk, its thick blastopore lips
      resemble the embryonic disk of the marsupial frog Gastrotheca riobambae and
      represent an interesting deviation from the gastrulation pattern observed in X.
      laevis.

PMID- 15470640
TI  - Distinct neural precursors in the developing human spinal cord.
AB  - Both embryonic and adult central nervous system have been shown to contain
      multipotent neural stem cells, but it is not yet clear whether they consist of a
      single or distinct populations of neural precursors. Since embryonic human neural
      precursors, particularly in the spinal cord, have not been extensively
      characterized, we have studied their behaviour at different days of gestation and
      in different culture conditions. Depending on dissociation and culture
      conditions, neurospheres which contain nestin- and vimentin-positive or only
      vimentin-positive neural precursors can be isolated. Whereas the former can be
      isolated only at early developmental stages, the latter appear to be present at
      all the stages examined, between 45 and 89 days of gestation. Furthermore,
      comparison of the effect of FGF, EGF and the two factors in combination on colony
      formation shows an additive effect of the two growth factors, indicating the
      existence of more than one type of neural precursor. Overall our results suggest
      that the human spinal cord contains distinct and dynamic populations of neural
      precursors which are developmentally regulated.

PMID- 15470641
TI  - MMTV-trBrca1 mice display strain-dependent abnormalities in vaginal development.
AB  - The breast cancer susceptibility gene Brca1 encodes a large multi-functional
      protein which is implicated as a caretaker of the genome, through its role in
      regulation of DNA damage response pathways, including apoptosis. Here we show
      that in mice expressing a dominant-negative Brca1 transgene on a BALB/c
      background, vaginal entrance remodeling is inhibited, and that the incidence of
      this phenotype is increased on a p53 +/- genotype. Given that this developmental
      process is mediated primarily by apoptosis, we hypothesized that disruption of
      BRCA1 may confer a resistance to apoptosis in normal epithelial cells. Consistent
      with this, we show that expression of this transgene in vitro leads to resistance
      to ionizing radiation induced cell killing in mammary epithelial cells. This is
      the first time that BRCA1 has been implicated in an apoptosis-mediated normal
      developmental process.

PMID- 15470642
TI  - Identification of new modes of Dd-STATa regulation of gene expression in
      Dictyostelium by in situ hybridisation.
AB  - Signal Transducers and Activators of Transcription (STATs) are transcription
      factors which lie at the end of cytokine and growth signal transduction pathways.
      Dictyostelium Dd-STATa is a functional homologue of metazoan STATs. It is
      activated by cAMP and, at the slug stage, it translocates into the nuclei of the
      tip cells, which are a subset of the anterior, prestalk A (pstA) cells. Here we
      searched for novel Dd-STATa regulated genes by in situ hybridisation. A set of 54
      cDNA clones whose gene expression patterns are known to be prestalk-specific
      (Maeda et al., 2003), were chosen as probes and we compared their expression
      patterns in parental and Dd-STATa-null strains. We identified 13 genes which are
      candidates for direct induction by Dd-STATa. In the parental strain, most of
      these genes are expressed in the cone shaped mass of pstAB cells which is located
      within the prestalk region. These cDNAs show little or no expression in the Dd
      STATa-null strain. This contrasts markedly with the paradigmatic ecmB gene which
      is expressed in pstAB cells in parental cells, but which is expressed throughout
      the prestalk zone in the Dd-STATa-null strain. We also identified several genes
      which are normally expressed in pstA cells, or throughout the prestalk region,
      but whose expression is markedly down-regulated in the null mutant. Again, this
      contrasts with markers derived from the paradigmatic, ecmA gene which are
      expressed normally in the Dd-STATa-null strain. The identification of these novel
      genes provides valuable tools to investigate the role of Dd-STATa.

PMID- 15470643
TI  - Should the management of heart failure become a new subspecialty?

PMID- 15470645
TI  - Age, functional capacity, and health-related quality of life in patients with
      heart failure.
AB  - BACKGROUND: Although heart failure disproportionately affects older persons and
      is associated with significant physical disability, existing data on physical
      limitations and health-related quality of life (HRQL) derive largely from studies
      of younger subjects. We compared the relationship between functional limitation
      and HRQL between older and younger patients with heart failure. METHODS AND
      RESULTS: We evaluated 546 outpatients with heart failure enrolled in a
      multicenter prospective cohort study. At baseline and 6 +/- 2 weeks later,
      functional status was assessed by New York Heart Association (NYHA)
      classification and 6-minute walk testing. HRQL was measured with the Kansas City
      Cardiomyopathy Questionnaire (KCCQ). Comparing older (age >65 years, n = 218) and
      younger patients (n = 328), we assessed baseline HRQL across strata of functional
      status. In the 484 patients who completed follow-up (194 older and 290 younger
      patients), we also assessed the changes in HRQL associated with changes in
      functional status over time. At baseline, older patients had better HRQL than
      younger patients (mean KCCQ score 60 +/- 25 versus 54 +/- 28, P = .005) in spite
      of worse NYHA class (mean 2.54 versus 2.35, P < .001) and lower 6-minute walk
      distances (824 +/- 378 versus 1064 +/- 371 feet, P < .001). After multivariable
      adjustment including baseline NYHA class, older age was independently correlated
      with better HRQL (beta = +7.9 points, P < .001). At follow-up, older patients
      with a deterioration in NYHA class experienced marked declines in HRQL compared
      with younger patients (mean HRQL change of -14.4 points versus +0.3 points,
      respectively, P < .001). Analyses using 6-minute walk distance as the functional
      measure yielded similar results. CONCLUSIONS: Although older patients with heart
      failure have relatively good HRQL in spite of significant functional limitations,
      they are at risk for worsening HRQL with further decline in functional status.
      These results underscore the importance of treatments aimed at maintaining
      functional status in older persons with heart failure, including those with
      significant baseline functional limitations.

PMID- 15470646
TI  - Hospitalized heart failure: rates and long-term mortality.
AB  - BACKGROUND: Heart failure has been called the "new epidemic of cardiovascular
      disease," but few studies have described key epidemiologic measures of the
      syndrome in geographically defined US populations. METHODS AND RESULTS: We
      obtained lists of discharge diagnosis codes in 1995 from 22 Minneapolis-St. Paul
      metropolitan area hospitals; identified patients 35 to 84 years old with a heart
      failure discharge code; and sampled and abstracted 50% of the hospital records.
      To identify heart failure-related hospitalizations, we applied 6 published
      definitions of the syndrome to the sample and selected cases that met at least 4
      of the 6 definitions (n = 2887). The patient cohort was followed for 5 to 6 years
      to ascertain deaths. The rate of hospitalized heart failure ranged from a few
      dozen hospitalized patients per 100,000 residents ages 35 to 44 years to more
      than 2000 per 100,000 residents ages 75 to 84, and was consistently higher among
      men than among women (age-adjusted rate ratio 1.46; 95% CI 1.39-1.54). Within 1
      year of the index admission, 37% of male patients and 30% of female patients have
      died-10 times the annual mortality of the source population. By the end of the
      follow-up, cumulative mortality reached 72% in men and 66% in women. In
      multivariable regression of the hazard of death on age, sex, and left ventricular
      ejection fraction (LVEF), age was a strong determinant of mortality and male
      patients had modestly higher hazard of death than female patients (adjusted
      hazard ratio, 1.29; 95% CI 1.18-1.41). LVEF was not a strong predictor of death.
      CONCLUSION: A heart failure-related hospitalization is a marker of grave
      prognosis: only one quarter to one third of the patients survives 5 years after
      admission. Both the risk of hospitalization for heart failure and the risk of
      subsequent death are moderately higher in men than in women. LVEF, when measured
      in the context of heart failure-related hospitalization, is not a strong
      predictor of death.

PMID- 15470647
TI  - Intermittent outpatient ultrafiltration for the treatment of severe refractory
      congestive heart failure.
AB  - BACKGROUND: Patients with severe congestive heart failure (CHF) become refractory
      to conventional medical therapy, leading to recurrent rehospitalizations. We
      examined the impact of intermittent outpatient ultrafiltration (UF), using either
      peritoneal dialysis or hemofiltration, on long-term clinical outcomes in patients
      with refractory CHF. METHODS AND RESULTS: We analyzed clinical and hemodynamic
      data in 19 consecutive patients with refractory CHF who received intermittent
      outpatient UF for at least 1 year between July 1998 and November 2002. The mean
      left ventricular ejection fraction of all 19 patients was 30.2 +/- 19.0%. All
      patients (100.0%) were New York Heart Association (NYHA) class IV. Only 5
      patients (26.3%) received peritoneal dialysis; the remaining 14 (73.7%) received
      hemofiltration. There were 6 patients with a normal left ventricular ejection
      fraction (45%). After UF was started, the number of patients that were considered
      inotrope-dependent was reduced from 86.4% to 36.8% (P < .005). Compared with the
      year before UF was initiated, the number of CHF hospitalizations during follow-up
      was reduced from 2.6 to 0.3 (P < .005), and the NYHA class was improved from 4 to
      3.1 (P < .005). Among all patients, 2 deaths were related to complications of UF,
      and cumulative 1-year survival was 63.2%. CONCLUSION: Our study suggests that UF
      is a safe, feasible therapy, but it needs further evaluation in carefully
      designed, prospective, randomized clinical trials. UF has the potential for
      offering another important therapeutic option for patients with severe and
      refractory CHF.

PMID- 15470648
TI  - Comparative costs of home positive inotropic infusion versus in-hospital care in
      patients awaiting cardiac transplantation.
AB  - BACKGROUND: Outpatient positive inotropic support combined with implantation of
      an automatic implantable cardioverter defibrillator (AICD) may be used as a
      successful bridge to cardiac transplantation in patients with end-stage heart
      failure. A detailed comparative cost analysis of this outpatient strategy versus
      in-hospital care has not been previously reported. METHODS AND RESULTS: Twenty
      one United Network for Organ Sharing 1B patients awaiting cardiac transplantation
      received continuous outpatient inotropic therapy for a total of 3070 patient
      days. Daily costs for outpatient and in-hospital treatment were calculated.
      Nonparametric decision analysis was used to determine the strategy with greatest
      cost savings (immediate hospital discharge after AICD implantation versus in
      hospital care). A threshold analysis was performed to test the robustness of the
      decision analysis model. The outpatient strategy realized an average savings of
      $71,300 to $120,500 per patient. Decision analysis showed that no fixed period of
      in-hospital monitoring was more cost-saving than immediate hospital discharge
      after AICD implantation. Threshold analysis revealed that AICD costs would need
      to exceed $82,000 (currently $62,000) or that the difference between the
      outpatient and the in-hospital costs would need to be < or = $475 per day for any
      other intermediate strategy to be considered cost-saving. CONCLUSION: Outpatient
      inotropic therapy combined with AICD implantation in selected patients awaiting
      cardiac transplantation is an effective cost-minimizing strategy.

PMID- 15470649
TI  - Depression and health status in patients with advanced heart failure: a
      prospective study in tertiary care.
AB  - BACKGROUND: Depression impairs health status among patients with coronary
      disease. The effect of depression on patients with heart failure has been studied
      to date only in hospitalized patients. METHODS AND RESULTS: Prospective cohort
      study of 113 outpatients with advanced heart failure. At baseline, 19% (n = 21)
      had major depression or dysthymia, 9% (n = 10) had minor depression, and 72% (n =
      82) had no current depression diagnosis. Repeated measures analyses of covariance
      adjusting for demographic and clinical differences demonstrated that the
      depression groups differed on observed function (6-minute walk distance [F = 4.8,
      P = .01]), and self-reported generic (SF-36) and disease-specific (Kansas City
      Cardiomyopathy Questionnaire) health status. Depression groups also differed in
      severity of self-reported breathlessness, chest pain, and fatigue. Subject- and
      spouse-reported role function also differed between the groups. Partial
      correlation (controlling for the same covariates) between baseline Hamilton
      Depression Scale scores and these outcomes was highly significant at baseline and
      follow-up. CONCLUSIONS: Depression is prospectively associated with poorer health
      status in patients with advanced heart failure. Physical and role function,
      symptom severity, and quality of life are all significantly affected.

PMID- 15470650
TI  - Variability in the clinical status of patients with advanced heart failure.
AB  - BACKGROUND: The importance of repeated clinical assessments of patients with
      heart failure is widely accepted. The frequency of such follow-up is not
      established and is likely to depend on the natural history and variability of
      patients' health status and the availability and use of appropriate treatments.
      METHODS AND RESULTS: We analyzed data from a multicenter prospective cohort study
      of heart failure outpatients comparing baseline variables including New York
      Heart Association (NYHA) class, summary score on the Kansas City Cardiomyopathy
      Questionnaire (KCCQ), and performance on a 6-minute walk test with results of a
      repeat evaluation at 6 weeks. We also compared patient and physician assessment
      of change in disease status among patients with advanced symptoms (NYHA class III
      with a recent antecedent hospitalization or class IV) and those with milder
      degrees of limitation (NYHA classes I, II, and stable III). Patients with
      advanced symptoms had greater short-term variability in health status as
      reflected by the KCCQ summary score and a visual analog scale. A greater
      proportion of patients with advanced heart failure experienced moderate or
      greater clinical change. Patient and physician global assessments were congruent
      with more direct measures of health status. CONCLUSION: Patients with advanced
      heart failure have greater short-term variability in status, supporting the need
      for frequent clinical follow-up and appropriate power calculations for clinical
      trials that are designed to measure meaningful changes over a short period.

PMID- 15470651
TI  - Independent and additional prognostic value of aminoterminal propeptide of type
      III procollagen circulating levels in patients with chronic heart failure.
AB  - BACKGROUND: In chronic heart failure (CHF), changes in the extracellular space
      contribute to cardiac dysfunction. We aimed to determine whether aminoterminal
      propeptide of type III procollagen (PIIINP), a marker of extracellular matrix
      turnover, might provide prognostic information in CHF patients. METHODS AND
      RESULTS: A total of 101 consecutive CHF patients (mean age 61.7 +/- 8.7 years,
      88% males) were followed up between 1999 and 2001. The combined endpoint of the
      study was death and hospitalization for heart failure. During follow-up there
      were 15 deaths and 11 hospitalizations for worsening heart failure. At the
      survival analysis, age (P = .02), New York Heart Association class (P = .014), s
      creatinine (P = .014), plasma-PIIINP (p-PIIINP) levels (P = .005), left
      ventricular ejection fraction (LVEF) (P = .0002), and a restrictive mitral
      filling pattern (P = .0003) predicted event-free survival. At the multivariate
      analysis, p-PIIINP levels predicted outcome independently of other clinical
      variables, hormones, and echocardiographic and exercise testing variables (P <
      .05 in all models). In patients with LVEF <31%, the presence of p-PIIINP >4.7
      microg/L levels was significantly associated with a higher risk of death and
      hospitalization as compared with the other patients (event-free survival rate at
      12 months: 45% versus 95%; at 24 months: 27% versus 88%; at 36 months: 18% versus
      85%, P < .0001). CONCLUSIONS: In patients with CHF, PIIINP levels predict outcome
      independently of clinical status, hemodynamics and hormonal activation. PIIINP
      levels provide additional prognostic information to that of left ventricular
      function alone, suggesting that it may reflect more than cardiac extracellular
      matrix turnover.

PMID- 15470652
TI  - Losartan improves regional left ventricular systolic and diastolic function in
      patients with hypertension: accurate evaluation using a newly developed color
      coded tissue doppler imaging technique.
AB  - BACKGROUND: Angiotensin II receptor antagonists have recently been accepted as
      antihypertensive therapy. Tissue Doppler imaging (TDI) has been developed as a
      noninvasive tool to assess quantitatively regional myocardial motion
      abnormalities. This study was designed to determine whether our newly developed
      technique of color-coded TDI may be a useful means of quantifying the improvement
      in regional left ventricular (LV) myocardial contractility and relaxation after
      treatment with losartan in patients with hypertension. METHODS AND RESULTS:
      Losartan (50 to 100 mg) was administered for 6 months to 37 previously untreated
      patients with essential hypertension. Averaged myocardial velocity profiles
      (MVPs) for color-coded TDI were recorded in the ventricular septum and LV
      posterior wall before and after treatment. Peak myocardial velocities and peak
      myocardial velocity gradients (MVGs) in the LV walls were determined during
      systole and early diastole. The plasma concentration of transforming growth
      factor (TGF)-beta1 also was measured in all patients. Blood pressure and plasma
      TGF-beta1 level decreased after initiation of losartan therapy. The LV mass index
      and LV meridional end-systolic wall stress also decreased after treatment with
      losartan. LV geometry changed from a pattern consistent with concentric
      hypertrophy to normal geometry in 10 patients and to a pattern consistent with
      concentric remodeling in 5 patients, and from concentric remodeling to normal
      geometry in 5 patients after treatment with losartan. The ratio of early to late
      diastolic filling for the transmitral flow velocity increased after losartan
      treatment. The peak systolic and early diastolic myocardial velocities and MVGs
      in the ventricular septum and LV posterior wall increased after treatment with
      losartan, although the values 6 months after treatment with losartan were still
      lower than those in normal individuals. There were good correlations between
      changes in plasma TGF-beta1 level and changes in systolic and early diastolic
      MVGs 6 months after losartan. However, there were no significant correlations
      between changes in the systolic blood pressure and LV end-systolic wall stress
      and changes in the TDI parameters. CONCLUSION: Losartan improves regional LV
      function in patients with hypertension. Our newly developed averaged MVP and MVG
      measurements may be useful for accurately evaluating regional LV myocardial
      contractility and relaxation in these patients.

PMID- 15470653
TI  - Prediction of mortality in chronic heart failure from peak oxygen consumption
      adjusted for either body weight or lean tissue.
AB  - BACKGROUND: Peak oxygen consumption (pVO2) reflects oxygen extraction from the
      skeletal muscles, but is routinely corrected for body weight. We hypothesized
      that correcting pVO2 for lean tissue rather than total body weight would improve
      the prediction of prognosis in patients with chronic heart failure (CHF). METHODS
      AND RESULTS: A total of 272 CHF outpatients (mean age 61 +/- 12 years, New York
      Heart Association [NYHA] class 2.3 +/- 0.8) underwent a cardiopulmonary exercise
      testing and body composition assessment by dual-energy X-ray absorptiometry.
      During a median follow-up of 608 days (range 8-3656), 75 patients died.
      Univariate survival analysis showed strong survival prediction from pVO2 adjusted
      for total weight or lean tissue (chi2 17.7, P < .001; chi2 27.5, P < .0001,
      respectively). Both predicted survival significantly in bivariate analysis, (chi2
      4.6, P = .032; chi2 16.6, P < .0001). The predictive effects were independent of
      exercise protocol (treadmill versus cycle ergometer) (both P < .001).
      Multivariate analysis showed that pVO2 adjusted for lean tissue had prognostic
      importance independently of NYHA class, ejection fraction, and ventilation and
      carbon dioxide production slope (P < .05 for each). In patients with NYHA class I
      and II (n = 160), pVO2 adjusted for lean tissue predicted outcome (P = .03).
      CONCLUSION: Adjustment for lean tissue instead for body weight increases the
      prognostic power of pVO2, particularly in patients with mild heart failure.

PMID- 15470654
TI  - Reduced pulmonary clearance of endothelin in congestive heart failure: a marker
      of secondary pulmonary hypertension.
AB  - BACKGROUND: Endothelin-1 (ET-1) levels are elevated in congestive heart failure
      (CHF) in relation with the severity of pulmonary hypertension. We evaluated
      whether a reduced pulmonary ET-1 clearance could contribute to this elevation.
      METHODS AND RESULTS: We determined pulmonary ET-1 clearance in 24 patients with
      CHF in relation with hemodynamics, plasma ET-1, and N-terminal pro-brain
      natriuretic peptide (NT-proBNP) levels. Pulmonary ET-1 extraction, measured by
      the single bolus indicator-dilution technique, was reduced to 32 +/- 14% in
      comparison to historic controls (47 +/- 7%). Plasma ET-1 clearance by the lungs
      (924 +/- 588 mL/min) was also much lower than in controls (1424 +/- 79 mL/min).
      Clearance correlated inversely with mean pulmonary artery pressure (PAP, r = 
      .47, P = .017) and pulmonary capillary wedge pressure (r = -.47, P = .017) and
      positively with the rate of left ventricular (LV) relaxation LV -dP/dt (r = .593,
      P = .004). After multivariate analysis, only mean PAP and LV -dP/dt were
      independently correlated with ET-1 clearance (r = -.40, P = .03, and r = .55, P =
      .005, respectively). Plasma ET-1 levels did not correlate with clearance (r =
      .038, P = .86), and there was no significant arteriovenous ET-1 gradient. There
      was a mild nonsignificant correlation between plasma ET-1 and pulmonary artery
      systolic pressure (r = .38, P = .06), but a strong correlation with right atrial
      pressure (r = .696, P < .0001) and NT-proBNP levels (r = .51, P = .001), which
      were maintained after multivariate linear regression (r = .60, P = .001, and r =
      .32, P = .04, respectively). CONCLUSION: Pulmonary ET-1 clearance is reduced in
      CHF in relation with the severity of pulmonary hypertension. This reduced
      clearance does not significantly modulate plasma ET-1 levels. Whether this is
      only a marker of secondary pulmonary hypertension or could modulate pulmonary
      vascular tone will require further studies.

PMID- 15470655
TI  - Eplerenone, a selective aldosterone blocker, improves diastolic function in aged
      rats with small-to-moderate myocardial infarction.
AB  - BACKGROUND: The incidence of cardiovascular diseases increases rapidly with age,
      and the elderly suffer higher morbidity and mortality. Aldosterone blockers have
      shown benefits in patients with left ventricular (LV) dysfunction and heart
      failure after myocardial infarction (MI). However, aldosterone blockade efficacy
      has not been explored in aged animals with MI. Methods and results Small-to
      moderate MI was induced by coronary artery ligation in 16-month old rats, divided
      into 3 groups: sham-operated (control, n = 9), MI (n = 9), and MI fed a diet
      containing eplerenone (120 mg/kg/day, MI+Eplerenone, n = 9) given 18 days
      postsurgery and up to sacrifice 3 months later. At sacrifice, untreated MI rats
      did not show overt systolic dysfunction but they had (1) echocardiographic
      evidences of impaired relaxation (increase of E wave deceleration time and of
      isovolumic relaxation time, decrease of peak E wave velocity), (2)
      hemodynamically impaired LV relaxation (LV -dP/dt from 7413 +/- 720 to 4956 +/-
      475 mm Hg/s, P < .05), and (3) significant increase of collagen content in LV
      interstitium (from 4.27 +/- 0.23 to 5.34 +/- 0.24%, P < .01) and in aorta (from
      19 +/- 1 to 24 +/- 2%, P < .05). Eplerenone normalized echocardiographic and
      hemodynamic evidences of diastolic dysfunction, as well as myocardial
      interstitial collagen and aortic fibrosis (all parameters statistically different
      from untreated MI). CONCLUSION: In aged rats with small to moderate MI,
      eplerenone normalized diastolic relaxation, possibly through a reduction of
      interstitial fibrosis.

PMID- 15470656
TI  - Improved balance between TIMP-3 and MMP-9 after regional myocardial ischemia
      reperfusion during AT1 receptor blockade.
AB  - BACKGROUND: Angiotensin II (AngII) modulates the balance between matrix
      metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), and AngII type 1
      receptor (AT1R) blockers (ARBs) limit left ventricular (LV) dysfunction and
      remodeling after acute ischemia-reperfusion (IR). Whether ARBs improve TIMP/MMP
      balance during IR has not been determined. METHODS AND RESULTS: We measured
      hemodynamics, LV function, MMP-2 and MMP-9, and TIMP-3 and TIMP-4 in the ischemic
      zone (IZ) and nonischemic zone (NIZ) after in vivo IR (90 minutes anterior
      ischemia; 120 minutes reperfusion) in 28 dogs that were randomized to sham, IR
      controls, and IR plus the ARB valsartan. In controls, IR induced LV dysfunction,
      infarction, and IZ remodeling; increased MMP-9 and decreased TIMP-3 in the IZ
      compared with the NIZ (low TIMP-3/MMP-9 ratio); and did not change MMP-2 or TIMP
      4. Compared with controls, valsartan (1) limited LV dysfunction, infarct size,
      and IZ remodeling; (2) increased MMP-2 and MMP-9 and TIMP-3 and -4 in the NIZ;
      and (3) increased TIMP-3 and the TIMP-3/MMP-9 ratio in the IZ, but did not change
      MMP-2 and TIMP-4. CONCLUSION: Valsartan-induced cardioprotection after IR is
      associated with enhanced TIMP-3 expression and improved TIMP-3/MMP-9 balance in
      the in vivo dog model.

PMID- 15470658
TI  - [Clinical and instrumental surveillance of the arteriovenous fistula].
AB  - Stenosis and thrombosis are the most important complications leading to vascular
      access failure in hemodialysis (HD). Aiming for an early access dysfunction
      diagnosis and elective repair of the failing access, the DOQI guidelines
      recommend that all HD patients undergo a program of regular monitoring and
      surveillance. The K/DOQI 2000 update identifies specific types of evaluation for
      dialysis accesses. First nephrologists should examine patients by inspecting,
      ausculting and palpating the access at least every 4-6 weeks when patients are
      not being dialyzed. In addition, access surveillance should be regularly
      performed by various techniques, i.e. urea recirculation test, dialysis venous
      pressure measurement and access blood flow assessment. Recently many methods have
      been proposed and implemented. Ultrasound dilution is the most commonly used.
      This technique relies on the change in ultrasound velocity when blood is diluted
      with a normal saline bolus at a known dialyzer blood flow rate, after the lines
      have been reversed. Following the use of blood ultrasound dilution, multiple
      technologies have been implemented for access flow measurement with line
      reversal, i.e. hematocrit (Hct) dilution, thermodilution, conductivity variation
      assessment. There are three other methods that do not require line reversal: i.e.
      transcutaneous access flow (TQA) assessment, glucose pump test (GPT) and the
      variable flow Doppler. Finally, duplex scanning can provide both the anatomy and
      blood flow of the access. With a Qa <600 mL/min or <1000 mL/min, but reduced by
      25% in 4 months, K/DOQI suggest performing angiography and eventual elective
      repair.

PMID- 15470659
TI  - [Bone complications of renal transplantation. How to identify and prevent them].
AB  - Bone disease is a very frequent complication after renal transplantation (RTx).
      The main features of transplant bone disease include the osteopenic-osteoporotic
      syndrome, often complicated by fractures, avascular osteonecrosis of bones, bone
      pain syndrome and growth retardation in the children. The bone loss is greater
      during the first 12 months after RTx and can reach the osteoporotic range in
      above 40% of patients, with a fracture rate of 2-3% per year. The story of bone
      disease over the long pre-uremic and uremic period is one of the main causal
      factors. After RTx, glucocorticoid therapy seems to play the major causal role.
      Much more disputed is the role of the other immunosuppressive drugs, of
      persistent secondary hyperparathyroidism, and age. Hypophosphatemia and some
      genetic factors could also affect bone loss after RTx. Diabetic patients are
      particularly prone to develop bone disease after RTx. The main prophylactic
      interventions consist in the optimal control of hyperparathyroidism during the
      pre-transplant period, prescribing parathyroidectomy for autonomous
      hyperparathyroidism, not-responding to medical therapy. After RTx, both
      bisphosphonate and vitamin D metabolites, variably associated with calcium
      supplementation, have been demonstrated to have some beneficial effect on bone
      loss, at least in the first year after RTx. However, there are no data about the
      possible efficacy of these treatments on fracture rate.

PMID- 15470660
TI  - [Quantitative bone ultrasonography: state of the art and perspectives].
AB  - Quantitative Ultrasound (QUS) is a relatively new method of bone assessment that
      measures the velocity of sound and the broadband ultrasound attenuation at
      different skeletal sites: heel and phalanges. This is a mobile, inexpensive, easy
      to perform and radiation-free technique, capable of assessing not only bone
      density, commonly measured by means of Single Energy X-ray Absorptiometry, SXA,
      Dual Energy X-ray Absorptiometry, DXA and Quantitative Computed Tomography, QCT,
      but also its elasticity and structure. QUS has been validated for diagnosis of
      osteoporosis and prevention of hip fractures. Very recently, QUS was also been
      applied to the study of uremic osteodistrophy, of female premenopausal
      osteoporosis, male osteoporosis and in paediatric population. Moreover, many
      studies in the dialysis population has also shown the effectiveness of QUS at the
      phalanges site in evaluating bone turn-over and bone osteopenia. QUS may be an
      useful tool for the nephrologist in the day by day monitoring of uremic
      osteodistrophy and secondary hyperparathyroidism.

PMID- 15470661
TI  - [Continuous medical education].
AB  - Continuing medical education is an essential element of state-of-the-art medical
      practice. Continuing medical education as structured today in most countries,
      must be able to guarantee the quality of continuing medical education and its
      independence. There should, therefore, be an independent professional body at
      national level responsible for assessing and guaranteeing both quality and
      independence. This body will also have the power to oversee the participation of
      medical specialists in continuing medical education. A system of credits should
      was developed to express the professional value of continuing medical education
      activities. Each activity is credited with a certain score, which can be awarded
      to the participating specialist. Continuing medical education should remain an
      ethical obligation subject to the disciplinary authority of the profession
      itself. Continuing medical education should be both an individual and also a
      collective obligation of the profession; in order to promote and make it
      effective, each member state must provide the means of making continuing medical
      education available to all physicians. For the above reason the CME is a
      strategic way to improve the quality of the health system. In Italy new way to
      obtain CME credits are going to be issue in the near future.

PMID- 15470662
TI  - [The treatment of osteodystrophy in dialyzed uremic patients: results of the
      first Sardinian audit].
AB  - BACKGROUND: Hyperphosphatemia in the uremic patient undergoing dialysis causes
      and makes the secondary hyperpharatyroidism progress. Nowadays it has a very
      important role in predicting mortality. The aim of the study was to assess by
      "Audit" to analyse adequacy of the Sardinian dialytic patients with reference to
      the optimal objective of the national and international guidelines. PATIENTS AND
      METHODS: The questionnaire of the audit was composed of 11 questions about the
      percentage distribution of: calcium in the dialysate, values of phosphoremia), Ca
      x P product, patients treated with vitamin D taking one or more phosphate
      binders, average dose, spKt/V > or = 1.2, serum aluminium, parathiroidectomy.
      RESULTS: We examined 1274 dialysis patients (93% on hemodialysis and 7% in CAPD)
      in 26 dialytic centers in our region (age 63.8 anni +/- 32.4; dialytic age 5.15
      +/- 5.06. Phosphorus ranges (mg/dL) P < 5.5: 61.3 +/- 23%; between 5.5 e 6.5:
      28.2 +/- 17.7%; and P > 6.5: 10.4 +/- 7.7%; Ca x P (<60): 77.8% +/- 16.6%;
      between 60-70: 16.8 +/- 13.4%; > 70: 4.99 +/- 4.7%. The more prescribed dialysate
      calcium was 1.5 mmol/L in HD (58.8%) HF (60.6%), HDF (51.6%) and CAPD (5.6%). PTH
      levels were: 31.1% (<120); 29.5% (120-250); 21.1% (250-450); 8% (450-600); 10.3%
      (>600). Patients on vitamin D: os daily 23.04 +/- 28%; post-dialysis boluses: os
      32.6 +/- 28, i.v. 10.6 +/- 9%; no therapy 32.7 +/- 22.7%. The percentage use of
      phosphorus binders: 48.5% calcium carbonate (2.9 g/d); 7.12% calcium acetate
      (1.34 g/d); 13.5% sevelamer (2.79 g/d); 10% total aluminium based (0.62 g/d). The
      aluminium is dosed in 11/26 dialysis units (32.3% of the population); 2.3% +/-
      0.9% of patients having Aluminium > 30 mcg/L. The dialytic patients have a Kt/V >
      or = 1.2: 80.1 +/- 19%. Parathyroidectomy incidences 1.8%. CONCLUSIONS: The data
      show good control of the average phosporous, there is a worrying percentage of
      patients with PTH values compatible with hypodynamic bone condition, lower and
      therefore safer calcium levels in the dialysate, poor aluminium control and low
      incidence of parathyroidectomy. In our experience the audit is a good way to
      verify and to correct the therapeutic choice in uremic osteodistrophy.

PMID- 15470663
TI  - [Large volume increase in a trastigian kidney].
AB  - With few exceptions renal volume is markedly reduced in patients with end-stage
      renal disease, a phenomenon which is almost always accompanied by a progressive
      loss of renal compliance secondary to renal structure fibrosis. We have observed
      a remarkable renal compliance during an episode of acute pyelonephritis in a
      patient on long-term dialysis.

PMID- 15470664
TI  - [From the Mailing List of the Italian Society of Nephrology: Pharmacological
      therapy and plasma exchange in the treatment of HCV-associated cryoglobulinemia].
AB  - The Mailing List SociSIN (ML-SIN) is beginning to develop, beside more
      experienced organisational topics, there is also some discussion on clinical
      topics. During the month of May, some messages requesting the opinion of
      experienced Colleagues on the use of plasma exchange in the cryoglobulinaemia
      correlated with HCV have risen an interesting debate on this argument. This issue
      of the review dedicated to the ML-SIN presents a short introduction dedicated to
      the definition, the main characteristics and the therapeutic bases of the
      cryoglobulinaemia associated to HCV. The messages on this topic are then
      summarised and, finally, the opinion of an expert on the matter is reported. The
      expert is chosen on the basis of the importance of his international scientific
      contribution to this particular topic.

PMID- 15470665
TI  - Fine structural correlates of the choroid plexus of the lateral cerebral
      ventricle of the human fetal brain.
AB  - The germinal matrix neuroepithelium and the choroidal fissure of the fetal
      choroid plexus commonly possess microvessels that are often poorly developed.
      There may be a reduction of type IV collagen that surrounds these fragile
      microvessels. During the first and second trimester of neural development, these
      microvessels are friable and can undergo intraventricular hemorrhage under a
      number of circumstances. Early subtle changes in the integrity of germinal matrix
      epithelium are not easily visualized by ultrasound. The current investigation
      employing scanning electron microscopy clearly defines subtle hemorrhagic events
      and tearing of the germinal matrix neuroepithelium in the brains of human
      fetuses. A 23-week-old fetus survived for 11 days but died from other causes. The
      choroid plexus of this fetus was compared with the choroid plexus and germinal
      matrix epithelium of a 22-week-old fetus that was the product of an elective
      termination due to severe anhydramnios of unknown origin and a 19-week-old male
      fetus from an elective termination. All tissues were autopsy material not
      requiring institutional review board approval.

PMID- 15470667
TI  - Evolution of the special senses in primates: past, present, and future.
AB  - The present special issue of The Anatomical Record is the result of a symposium
      entitled Evolution of the Special Senses in Primates. Considered together, the
      special senses of primates are remarkable because they constitute a singular and
      definitive suite of mammalian characteristics. Examining their evolution is
      pivotal for understanding the origin and present-day variation of primate
      behavior and ecology. Accordingly, the 14 articles assembled here consider the
      different constraints and opportunities associated with the uptake and use of
      physical and chemical stimuli. The present issue brings together experts on
      different primate sensory modalities and stresses events at the sensory
      periphery, where the organism is exposed to and comes into contact with its
      environment. Key topics include color vision, the genetics of olfaction, the
      morphological basis and significance of chemical communication, and the neural
      organization and scaling of primate sensory systems. The result is a special
      issue that both reflects our current understanding of primate sensory modalities
      and challenges certain fundamental assumptions concerning their evolution.

PMID- 15470668
TI  - High-resolution computed tomography study of the cranium of a fossil anthropoid
      primate, Parapithecus grangeri: new insights into the evolutionary history of
      primate sensory systems.
AB  - Extant anthropoids have large brains, small olfactory bulbs, and high-acuity
      vision compared with other primates. The relative timing of the evolution of
      these characteristics may have important implications for brain evolution. Here
      computed tomography is used to examine the cranium of a fossil anthropoid,
      Parapithecus grangeri. It is found that P. grangeri had a relatively small brain
      compared with living primates. In addition, it had an olfactory bulb in the
      middle of the range for living primates. Methods for relating optic foramen area
      and other cranial measurements to acuity are discussed. Multiple regression is
      used to estimate retinal ganglion cell number in P. grangeri. Given currently
      available comparative data, P. grangeri seems to have had retinal ganglion cell
      counts intermediate for living primates, overlapping with the upper end of the
      range for strepsirrhines and possibly with the lower end for anthropoids.

PMID- 15470669
TI  - Three-dimensional structure and evolution of primate primary visual cortex.
AB  - In this study, three-dimensional reconstructions of primate primary visual cortex
      (V1) were used to address questions about its evolution. The three-dimensional
      shape of V1 in anthropoids is significantly longer and narrower than in
      strepsirrhines. This difference is an effect of clade and is not due to
      differences in activity pattern or V1 size. New measurements of V1 volume were
      also provided in order to reassess V1 size differences between strepsirrhines and
      anthropoids. It was found that for a given lateral geniculate nucleus (LGN)
      volume, anthropoids have a significantly larger V1 than strepsirrhines do. This
      is important since LGN is the principal source of V1's input. Finally,
      independent contrasts analysis was used to examine the scaling of V1 relative to
      LGN, the rest of cortex, and the rest of the brain. It was confirmed that V1
      scales with positive allometry relative to LGN. A number of possible explanations
      for scaling are discussed. V1 scaling may have to do with the tendency of large
      brains to be more compartmentalized than small brains, or V1 scaling might
      reflect the geometry of information representation.

PMID- 15470670
TI  - Comparative morphology of the eye in primates.
AB  - Comparative studies of mammalian eye morphology have shown that relative cornea
      size is an important correlate of visual ecology. Nocturnal species tend to have
      large corneas relative to eye size as an adaptation for increasing visual
      sensitivity. By contrast, diurnal species tend to have smaller corneas relative
      to eye size because their eye morphology maximizes visual acuity. Although
      qualitative analyses suggest that activity pattern may have a similar influence
      on eye morphology in primates, various current hypotheses have proposed that
      either diurnal anthropoids or diurnal lemurs have visual systems that diverge
      from those of other diurnal mammals. The goal of this analysis is to quantify the
      relationship between eye morphology and activity pattern in primates and to
      determine whether primates exhibit variation in eye morphology comparable to that
      of other mammals. Data on eye size and cornea size were collected for 147
      specimens of 55 primate species. These data reveal that, within primate
      suborders, diurnal species have significantly smaller relative cornea sizes than
      nocturnal or cathemeral species. Both haplorhines and strepsirrhines thus exhibit
      variation in eye morphology that is consistent with functional expectations.
      However, comparisons between the two primate suborders demonstrate that
      haplorhines and strepsirrhines differ significantly in eye morphology. Whereas
      strepsirrhines have relative cornea sizes that are similar to nonprimate mammals
      of comparable activity pattern, diurnal anthropoids have smaller relative cornea
      sizes than most nonprimate mammals. This derived eye morphology in anthropoids
      probably evolved in the anthropoid stem lineage as a result of selection for
      highly acute diurnal vision.

PMID- 15470671
TI  - On the relationship between orbit orientation and binocular visual field overlap
      in mammals.
AB  - The orbital apertures of Primates are among the most convergent (i.e., facing in
      the same direction) among mammals. It is often assumed that orbit convergence is
      associated with binocular visual field overlap and stereoscopic depth perception
      in primates. Likewise, it is also assumed that orbit orientation reflects the
      shape of the visual field across mammals. To date, however, no study has
      demonstrated that orbit and visual field orientation are correlated, much less
      comparable, across mammals. In this study, data on orbit convergence were
      collected for a representative sample of mammals for which data on the extent of
      the visual field are available. Both standard and phylogenetically controlled
      comparisons were made. The results demonstrate that orbit convergence and
      binocular visual field overlap are significantly correlated and display a linear
      relationship. Based on orbit convergence, Primates as a group have the largest
      binocular visual fields among mammals.

PMID- 15470672
TI  - Primate auditory diversity and its influence on hearing performance.
AB  - The auditory region contains numerous structures that have proven useful for
      phylogenetic classification at various taxonomic levels. However, little work has
      been done in primates relating differences in morphology to variations in hearing
      performance. This study documents anatomical and physiological distinctions
      within primates and begins to address the functional and evolutionary
      consequences of these and other auditory features. The dimensions of the outer
      ear (pinna) were measured in cadaveric specimens representing nearly every
      primate family and used to calculate a shape ratio (height/width). It was found
      that nonanthropoids have a significantly higher ratio than anthropoids, although
      the actual height was not found to differ. This indicates that most
      nonanthropoids have ears that are tall and narrow, whereas monkeys and apes are
      characterized by ears with more equal height and width dimensions. Eardrum area,
      stapedial footplate area, and ossicular lever arm lengths were measured in dried
      specimens to calculate an impedance transformer ratio. A distinction was found
      between anthropoids and strepsirrhines, with the latter group having a
      transformer ratio indicative of a higher percentage of acoustic energy
      transmission through the middle ear. Audiogram data were gathered from the
      literature to analyze hearing sensitivity and it was found that platyrrhines
      illustrate more low-frequency sensitivity than like-sized lorisoids. The effects
      of intraspecific variation on the audiogram results were also examined and were
      found to produce similar results as the analysis using species mean threshold
      values. Lastly, correlations between morphological and audiogram variables were
      examined. Several measures of hearing sensitivity were found to be correlated
      with pinna shape but correlations with middle ear transmission properties were
      weaker. In addition to using traditional statistical techniques, phylogenetic
      corrective methods were applied to address the problem of statistical
      nonindependence of the data and the results of both analyses are compared. These
      findings are discussed with respect to how sensory adaptations and phylogenetic
      history may be related to the current radiation of primates.

PMID- 15470673
TI  - Evolution of somatosensory and motor cortex in primates.
AB  - Inferences about how the complex somatosensory systems of anthropoid primates
      evolved are based on comparative studies of such systems in extant mammals.
      Experimental studies of members of the major clades of extant mammals suggest
      that somatosensory cortex of early mammals consisted of only a few areas,
      including a primary area, S1, bordered by strip-like rostral and caudal
      somatosensory fields, SR and SC. In addition, the second somatosensory area, S2,
      and the parietal ventral area, PV, were probably present. S1, S2, and PV were
      activated independently via parallel projections from the ventroposterior
      nucleus, VP. Little posterior parietal cortex existed, and it was unlikely that a
      separate primary motor area, M1, existed until placental mammals evolved. Early
      primates retained this basic organization and also had a larger posterior
      parietal region that mediated sensorimotor functions via connections with motor
      and premotor areas. The frontal cortex included M1, dorsal and ventral premotor
      areas, supplementary motor area, and cingulate motor fields. Ventroposterior
      superior and ventroposterior inferior nuclei were distinct from the
      ventroposterior nucleus in the thalamus. In early anthropoid primates, areas S1,
      SR, and SC had differentiated into the fields now recognized as areas 3b, 3a, and
      1. Areas 3b and 1 contained parallel mirror-image representations of cutaneous
      receptors and a parallel representation in area 2 was probable. Serial processing
      became dominant, so that neurons in areas 1, S2, and PV became dependent on area
      3b for activation. Posterior parietal cortex expanded into more areas that
      related to frontal cortex. Less is known about changes that might have occurred
      with the emergence of apes and humans, but their brains were larger and posed
      scaling problems most likely solved by increasing the number of cortical areas
      and reducing the proportion of long connections.

PMID- 15470674
TI  - Meissner corpuscles and somatosensory acuity: the prehensile appendages of
      primates and elephants.
AB  - Meissner corpuscles (MCs) are specialized mechanoreceptors located exclusively in
      the papillae of glabrous skin. They are confined largely to cutaneous pads of the
      extremities and respond to transient, phasic, or vibratory stimuli. Though absent
      in most eutherian taxa, MCs are reported in all primates studied, being most
      developed in modern humans. The location of MCs between the internal ridges of
      the epidermis indicates they are well situated to detect friction or deformation
      at the external surface. Accordingly, MCs are hypothesized to provide primates
      generally with an enhanced tactile perception. However, the selective pressures
      favoring greater somatosensory acuity in primates are seldom considered.
      Interestingly, primate digital dexterity varies greatly. In general, dexterity
      improves with the extent to which foraging requires food manipulation or textural
      evaluation. This observation implies that MC density could vary accordingly. Here
      we report on the density of MCs in five anthropoid taxa selected to represent
      diverse dietary regimes. Results show that greater MC density correlates with the
      extent to which primates are frugivorous; however, locomotor and/or phylogenetic
      effects cannot be discounted.

PMID- 15470675
TI  - Comparative analysis of the role of olfaction and the neocortex in primate
      intrasexual competition.
AB  - In strepsirrhine primates, the accessory olfactory system plays an important role
      in intrasexual competition. However, it does not play the same role in most
      haplorhines. In these primates, the main olfactory system and neocortex may have
      evolved to serve similar functions as the accessory olfactory system in
      strepsirrhines. To test these hypotheses, the relative size of the main olfactory
      bulb and neocortex were analyzed for associations with male and female
      competition frequency and intensity (categorized as low or high). Because
      neocortex size and competition intensity are associated with diet, only
      frugivorous species were analyzed (catarrhines, n = 7; platyrrhines, n = 8).
      Neither the size of the main olfactory bulb nor the neocortex was significantly
      associated with intrasexual competition among males. However, neocortex size was
      related to the frequency of female competition. Because the main olfactory system
      and neocortex both serve multiple purposes, there may not be a single behavioral
      variable that has selected for their size. Furthermore, categorization of male
      and female competition intensity reflects physically aggressive behavior. Use of
      the neocortex for social manipulation may allow males to obtain copulations and
      females to obtain food resources despite poor physical fighting abilities and low
      dominance rank.

PMID- 15470676
TI  - Expression of neuron-specific markers by the vomeronasal neuroepithelium in six
      species of primates.
AB  - Vomeronasal organ (VNO) morphology varies markedly across primate taxa. Old World
      monkeys display no postnatal VNO. Humans and at least some apes retain a
      vestigial VNO during postnatal life, whereas the strepsirrhines and New World
      Monkeys present a morphologically well-defined VNO that, in many species, is
      presumed to function as an olfactory organ. Available microanatomical and
      behavioral studies suggest that VNO function in these species does not precisely
      duplicate that described in other mammalian taxa. The questions of which species
      retain a functional VNO and what functions they serve require inquiry along
      diverse lines but, to be functional, the vomeronasal epithelium must be neuronal
      and olfactory. We used immunohistochemistry to establish these criteria in six
      primate species. We compared the expression of two neuronal markers, neuron
      specific beta-tubulin (BT) and protein gene product 9.5, and olfactory marker
      protein (OMP), a marker of mature olfactory sensory neurons, in paraffin-embedded
      VNO sections from two strepsirrhine and four haplorhine species, all of which
      retain morphologically well-defined VNOs during postnatal life. The infant
      Eulemur mongoz, adult Otolemur crassicaudatus, neonatal Leontopithicus rosalia,
      and adult Callithrix jacchus express all three proteins in their well-defined
      vomeronasal neuroepithelia. The infant Tarsius syrichta showed some BT and OMP
      immunoreactivity. We establish that two strepsirrhine species and at least some
      New World haplorhines have mature sensory neurons in the VNO. In contrast, at all
      ages examined, Saguinus geoffroyi VNO expresses these markers in only a few
      cells.

PMID- 15470677
TI  - Facts, fallacies, fears, and frustrations with human pheromones.
AB  - Among primates in general, pheromones are of variable importance to social
      communication. Data on humans have generated the greatest controversy regarding
      the existence of pheromonal communication. In this review, the likelihood of
      pheromonal communication in humans is assessed with a discussion of chemical
      compounds produced by the axilla that may function as pheromones; the likelihood
      that the vomeronasal organ (VNO), a putative pheromone receptor organ in many
      other mammals, is functional in humans; and the possible ways pheromones operate
      in humans. In the human axilla, the interactions between the cutaneous microflora
      and axillary secretions render this region analogous to scent glands found in
      other primates. Both the chemistry of axillary secretions and their effects on
      conspecifics in humans appear to be analogous to other mammalian pheromone
      systems. Whichever chemical compounds serve a pheromonal function in humans,
      another unknown is the receptor. Although the VNO has been implicated in the
      reception of pheromones in many vertebrates, it is not the only pathway through
      which such information has access to the central nervous system; there is ample
      evidence to support the view that the olfactory epithelium can respond to
      pheromones. Furthermore, if a chemical activates receptors within the VNO, this
      does not necessarily mean that the compound is a pheromone. An important caveat
      for humans is that critical components typically found within the functioning VNO
      of other, nonprimate, mammals are lacking, suggesting that the human VNO does not
      function in the way that has been described for other mammals. In a broader
      perspective, pheromones can be classified as primers, signalers, modulators, and
      releasers. There is good evidence to support the presence of the former three in
      humans. Examples include affects on the menstrual cycle (primer effects);
      olfactory recognition of newborn by its mother (signaler); individuals may exude
      different odors based on mood (suggestive of modulator effects). However, there
      is no good evidence for releaser effects in adult humans. It is emphasized that
      no bioassay-guided study has led to the isolation of true human pheromones, a
      step that will elucidate specific functions to human chemical signals.

PMID- 15470678
TI  - Convergence of sensory systems in the orbitofrontal cortex in primates and brain
      design for emotion.
AB  - In primates, stimuli to sensory systems influence motivational and emotional
      behavior via neural relays to the orbitofrontal cortex. This article reviews
      studies on the effects of stimuli from multiple sensory modalities on the brain
      of humans and some other higher primates. The primate orbitofrontal cortex
      contains the secondary taste cortex, in which the reward value of taste is
      represented. It also contains the secondary and tertiary olfactory cortical
      areas, in which information about the identity and also about the reward value of
      odors is represented. A somatosensory input is revealed by neurons that respond
      to the viscosity of food in the mouth, to the texture (mouth feel) of fat in the
      mouth, and to the temperature of liquids placed into the mouth. The orbitofrontal
      cortex also receives information about the sight of objects from the temporal
      lobe cortical visual areas. Information about each of these modalities is
      represented separately by different neurons, but in addition, other neurons show
      convergence between different types of sensory input. This convergence occurs by
      associative learning between the visual or olfactory input and the taste. In that
      emotions can be defined as states elicited by reinforcers, the neurons that
      respond to primary reinforcers (such as taste and touch), as well as learn
      associations to visual and olfactory stimuli that become secondary reinforcers,
      provide a basis for understanding the functions of the orbitofrontal cortex in
      emotion. In complementary neuroimaging studies in humans, it is being found that
      areas of the orbitofrontal cortex are activated by pleasant touch, by painful
      touch, by taste, by smell, and by more abstract reinforcers such as winning or
      losing money. Damage to the orbitofrontal cortex in humans can impair the
      learning and reversal of stimulus-reinforcement associations and thus the
      correction of behavioral responses when these are no longer appropriate because
      previous reinforcement contingencies change. It is striking that humans and other
      catarrhines, being visual specialists like other anthropoids, interface the
      visual system to other sensory systems (e.g., taste and smell) in the
      orbitofrontal cortex.

PMID- 15470679
TI  - Explorations into new reaction chemistry.
AB  - This Review describes the basic concepts that have guided our exploration of new
      chemical reactions by giving examples of results from my research group. Our
      strategy of carrying out research is to investigate three to four different
      topics at a time so we can gather as many results as possible. These may at first
      appear unrelated to each other but may have the potential to be united into a
      greater hypothesis after repeated feedback. Three scenarios from our research are
      presented: the "oxidative-reductive condensation reaction" devised in 1960, which
      after an interval of nearly 40 years brought forth the new concept of using
      compounds of structure Ph(2)POR as reducing reagents; the "TiCl(4)-aldol
      reaction" of 1973 that eventually led to the present "base-promoted aldol
      reaction" through a chain of ideas; and the "glycosylation reaction using
      fluorosugars" from 1984 which recently bloomed into "stereocontrolled
      glycosylation". Thus, it can be said that by reviewing what we had done before,
      we were able to expand on it to achieve new outcomes.

PMID- 15470681
TI  - Natural history of disease progression in patients who fail to achieve an
      undetectable prostate-specific antigen level after undergoing radical
      prostatectomy.
AB  - BACKGROUND: To the authors' knowledge, the natural history of disease progression
      to distant metastasis is unknown in men who fail to achieve an undetectable
      prostate-specific antigen (PSA) level after radical retropubic prostatectomy
      (RRP),. The authors assessed the clinical outcome of men with a persistently
      detectable PSA level after RRP for clinically localized prostate carcinoma.
      METHODS: Between 1989 and 2002, 160 men failed to achieve an undetectable PSA
      level (>/= 0.1 ng/mL) after undergoing RRP for clinically localized prostate
      carcinoma. No patient received adjuvant therapy before documented metastasis. The
      Kaplan-Meier method was used to estimate distant metastasis-free survival.
      Univariate and multivariate Cox proportional hazards regression was used to
      assess the ability of clinical and pathologic variables to predict distant
      metastasis-free survival. RESULTS: The probability of distant metastasis-free
      survival at 3 years, 5 years, and 10 years was reported to be 68%, 49%, and 22%,
      respectively. Seventy-five men (47%) developed distant metastases after RRP
      (median time to metastases of 5.0 years; range, 0.5-13 years). The combination of
      RRP Gleason score, seminal vesicle status, and lymph node status resulted in 3
      risk groups for the prediction of distant metastasis-free survival (hazards ratio
      [HR] = 1.6; P < 0.01). The slope of PSA changes approximately 3-12 months after
      RRP at a cutoff value >/= 0.05 was found to be even more predictive of distant
      metastasis-free survival (HR = 2.9; P < 0.01). CONCLUSIONS: Many patients
      remained free of metastatic disease for an extended period despite failing to
      achieve an undetectable PSA level after undergoing RRP for clinically localized
      prostate carcinoma. However, other patients experienced rapid disease progression
      to distant metastasis. The authors defined clinical (PSA slope) and pathologic
      (Gleason score) prognostic variables to help identify those patients with a
      higher risk of developing distant metastasis after undergoing RRP.

PMID- 15470680
TI  - Abnormal PcG protein expression in Hodgkin's lymphoma. Relation with E2F6 and
      NFkappaB transcription factors.
AB  - The Polycomb group (PcG) of proteins comprises a family of repressors of homeobox
      genes that play key roles in body formation, haematopoiesis and cell cycle
      control. In this study, a large-scale analysis of PcG protein expression (BMI1,
      MEL18, PH1, RNF2, RING1, and RYBP) was performed in 321 Hodgkin's lymphoma (HL)
      biopsies and in reactive lymphoid tissues using tissue microarrays. The relevance
      of PcG proteins in HL was also investigated by the simultaneous analysis of PcG
      and other proteins involved in the control of cell cycle, transcription machinery
      and lymphoid differentiation. The analysis revealed increased expression of a set
      of PcG proteins (particularly RYBP and BMI1) in tumour cells in comparison with
      reactive lymphoid tissue. One of the most striking findings was anomalous RYBP
      expression in 55% of classical HL cases associated with an unfavourable response
      to treatment and shorter survival. The data obtained in this study also show an
      association of PcG proteins with E2F6 and NFkappaB transcription factors. The
      statistical relationship between PcG and NFkappaB activation was further explored
      in HL-derived cell lines treated with curcumin, an NFkappaB inhibitor, and
      TNFalpha. Up- or downregulation of MEL18 was paralleled by loss or gain of
      activated NFkappaB, which suggests that NFkappaB may regulate expression of this
      protein. Investigation of the relationship between E2F6 and RING1 by
      immunofluorescence and confocal analysis, in HL cell lines and paraffin sections,
      revealed co-expression of both proteins in the same tumour cells. These results
      allow us to propose that the formation of transcription complexes with E2F6 may
      modify the functional status of PcG proteins in HSR cells.

PMID- 15470683
TI  - Psychological and educational factors: better predictors of work status than FEV1
      in adults with cystic fibrosis.
AB  - Now that more individuals with cystic fibrosis (CF) are living into adulthood,
      vocational attainment is an increasingly important consideration. Work is a key
      factor in quality of life. The purpose of the present paper was to evaluate the
      factors that are associated with work status in 183 adults with CF. Approximately
      half of the participants were working at the time of evaluation, an impressive
      figure given that the mean forced expired volume in 1 sec (FEV1) was 31.9%. The
      average number of hours worked was 32.7 hr/week. The majority of individuals were
      employed in professional, technical, or managerial occupations (accounting,
      teaching, law, or social work). A third were employed in clerical and sales
      occupations, and the remaining individuals were employed in a wide range of other
      occupations (hotel manager, undercover shopper, artist, or dental technician).
      Interestingly, FEV1 and age did not differentiate between subjects who were
      working and those who were not. Individuals who were working had significantly
      lower depression scores and a higher educational level than those who were not
      working. Future research is needed to determine whether it is the increased
      socialization and the resulting social support that may come from a work
      environment, or a reduction in financial stress because of better income and
      health benefits that helps to explain this difference. Alternatively, work may
      serve as a distraction from the symptoms of CF. It is likely that those with
      higher educational levels had more professional jobs that were more easily
      modified as health declined. Future research needs to assess how career choices
      are made, and what factors into a patient's decision to keep working.

PMID- 15470684
TI  - Children with smoking parents have a higher airway resistance measured by the
      interruption technique.
AB  - Children exposed to environmental tobacco smoke, during or after pregnancy, are
      known to have decreased lung function. So far this has been measured using
      spirometry in schoolchildren and invasive techniques in newborns. The
      interruption technique (Rint) is a noninvasive technique to measure airway
      resistance in preschool children. Our aim in this study was to investigate the
      effect of passive smoke exposure on Rint values in preschool and school-aged
      children. Rint values were obtained from 557 children in two nursery and two
      primary schools in the north of the Netherlands. Besides information on parental
      smoking habits, we collected data on characteristics that might affect airway
      resistance (respiratory symptoms, atopy, and family history for asthma), using a
      short questionnaire. Multiple linear regression was used to estimate the
      associations of these characteristics with Rint, for the whole group as well as
      for the preschool group separately. Atopy or a positive family history for asthma
      did not affect Rint values in the total group of 4-12-year-olds. However, as may
      be expected, height, age, weight, and having respiratory symptoms were associated
      with Rint. Moreover, Rint was significantly increased if parents smoked three or
      more cigarettes a day in the presence of their child. This result remained after
      subgroup analysis in the preschool children (4-6 years old). We conclude that
      passive smoke exposure is associated with a significantly higher airway
      resistance in preschool and school-aged children measured by Rint.

PMID- 15470686
TI  - Determination of enrofloxacin and its primary metabolite, ciprofloxacin, in pig
      tissues. Application to residue studies.
AB  - A simple and sensitive HPLC method has been developed for the simultaneous
      determination of enrofloxacin (ENR) and ciprofloxacin (CIP) in pig tissue using
      difloxacin (DIF) as internal standard. Tissue sample preparations were carried
      out by adding phosphate buffer (pH 7.4, 0.1 m), followed by extraction with
      trichloromethane. Fluoroquinolones were separated on a reversed-phase column and
      eluted with aqueous buffer solution-acetonitrile (80:20, v/v). The concentrations
      of CIP, ENR and DIF eluted from the column, with retention times of 2.20, 2.73
      and 4.38 min, respectively, were monitored by fluorescence detection at
      lambda(ex) 276 and lambda(em) 442 nm. The detection and quantitation limit were 8
      and 25 ng/g, respectively, for both compounds. Standard curves were linearly
      related to concentration in the range 25-400 ng/g. The consequences of the
      introduction of minor reasonable variations (ruggedness studies) have also been
      analysed. Finally, the measurement of the tissue levels of ENR and CIP in the pig
      tissues after oral administration confirmed the utility of the proposed method.

PMID- 15470687
TI  - Simultaneous determination of niflumic acid and its prodrug, talniflumate in
      human plasma by high performance liquid chromatography.
AB  - A high-performance liquid chromatographic (HPLC) method has been developed for
      the simultaneous determination of niflumic acid and its prodrug, talniflumate, in
      human plasma. Niflumic acid and talniflumate were eluted isocratically with
      methanol-water (73:27, v/v, adjusted to pH 3.5 by acetic acid) at a fl ow rate of
      1 mL/min. Indomethacin was used as an internal standard. Signals were monitored
      by an UV detector at 288 nm. Retention times of indomethacin, niflumic acid and
      talniflumate were 5.9, 7.2 and 13.5 min, respectively. Calibration plots were
      linear over the range 50-5000 ng/mL for niflumic acid and 100-5000 ng/mL for
      talniflumate. The limits of quantitation were 50 ng/mL for niflumic acid and 100
      ng/mL for talniflumate. The intra- and inter-day relative standard deviations
      (RSD) of niflumic acid and talniflumate were less than 10% and the accuracies
      were higher than 90%. This method is rapid, sensitive and reproducible for the
      determination of niflumic acid and talniflumate in human plasma.

PMID- 15470688
TI  - Virtual microscopy for learning and assessment in pathology.
AB  - Virtual slides are high-magnification digital images of tissue sections, stored
      in a multi-resolution file format. Using appropriate software, these slides can
      be viewed in a web browser in a manner that closely simulates examination of
      glass slides with a real microscope. We describe the successful implementation of
      teaching microscopic pathology with virtual slides and, for the first time, their
      use in summative assessment. Both students and teaching staff readily adapted to
      the use of virtual microscopy. Questionnaire feedback from students strongly
      indicated that virtual slides solved a number of problems in their learning,
      while providing good to excellent image quality. A deliberate policy of
      allocating two students per workstation promoted collaboration and helped to
      maintain interest in microscopic pathology. The use of a secure browser
      facilitated assessment using virtual slides, with no technical or security issues
      arising despite high peak demand. The new Medicine programme at the University of
      New South Wales will exclusively utilize virtual microscopy for the study of both
      histology and histopathology. We believe that the use of high-quality learning
      resources such as virtual slides can ensure that microscopic examination of
      tissues remains both meaningful and interesting.

PMID- 15470689
TI  - An insight into a novel class of self-assembled porphyrins: geometric structure,
      electronic structure, one- and two-photon absorption properties.
AB  - We have theoretically investigated a series of butadiyne-linked porphyrin
      derivatives that exhibit large two-photon absorption (TPA) cross sections in the
      visible-IR range. The electronic structure, one-photon absorption (OPA), and TPA
      properties have been studied in detail. We found that the introduction of a
      butadiyne linkage and the increase of the molecular dimensionality from monomer
      to dimer determine the OPA intensities of Q band and Soret band, respectively. A
      most important role for the enhancement of the TPA cross section is played by
      introducing a butadiyne bridge. The complementary coordination and the
      combination of the terminal free base and the core zinc porphyrin are also two
      effective factors for the enhancement of the TPA efficiency. The dimer with two
      porphyrins linked at meso-positions by a butadiyne linkage results in a maximum
      TPA cross section (79.35 x 10(-48) cm4 s per photon). Our theoretical findings
      are consistent with the recent experimental observations. This series of
      porphyrin derivatives as promising TPA materials are the subject of further
      investigation.

PMID- 15470690
TI  - Novel methods of automated structure elucidation based on 13C NMR spectroscopy.
AB  - Three new approaches for automated structure elucidations of organic molecules
      using NMR spectroscopic data were introduced recently. These approaches apply a
      neural network 13C NMR chemical shift prediction method to rank the results of
      structure generators by their agreement of the predicted and experimental
      chemical shifts. These three existing implementations are compared using
      realistic example molecules. The applicability and reliability of such approaches
      is addressed.

PMID- 15470691
TI  - Electron delocalization in linearly pi-conjugated systems: a concept for
      quantitative analysis.
AB  - Donor- and/or acceptor-substituted pi-conjugated systems represent an important
      class of compounds in organic chemistry. However, up to now, a general method to
      quantitatively address the efficiency of a conjugated path is still missing. In
      this work, a novel computational approach based on deletion energies and on
      second-order orbital interaction energies in a natural bond orbital (NBO) scheme
      is employed to quantitatively assess ("measure") delocalization energies.
      Moreover, the purpose of this work is to assess the efficiency of distinct pi
      conjugated paths, that is, geminal, cis, and trans, as well as to predict the
      impact of substituents on a given backbone. This study is focused on various mono
      , di-, tri-, and tetrasubstituted tetraethynylethenes (TEEs). These model systems
      are suitable for our analysis, because they offer distinct conjugation paths
      within the same molecule, and can also be substituted in multiple ways.
      Differences between conjugation paths, the effect of neighbor paths, and the
      impact of donor and acceptor substituents on the various paths are discussed.

PMID- 15470692
TI  - Hydrogen bonding of water confined in mesoporous silica MCM-41 and SBA-15 studied
      by 1H solid-state NMR.
AB  - The adsorption of water in two mesoporous silica materials with cylindrical pores
      of uniform diameter, MCM-41 and SBA-15, was studied by 1H MAS (MAS=magic angle
      spinning) and static solid-state NMR spectroscopy. All observed hydrogen atoms
      are either surface -SiOH groups or hydrogen-bonded water molecules. Unlike MCM
      41, some strongly bound water molecules exist at the inner surfaces of SBA-15
      that are assigned to surface defects. At higher filling levels, a further
      difference between MCM-41 and SBA-15 is observed. Water molecules in MCM-41
      exhibit a bimodal line distribution of chemical shifts, with one peak at the
      position of inner-bulk water, and the second peak at the position of water
      molecules in fast exchange with surface -SiOH groups. In SBA-15, a single line is
      observed that shifts continuously as the pore filling is increased. This result
      is attributed to a different pore-filling mechanism for the two silica materials.
      In MCM-41, due to its small pore diameter (3.3 nm), pore filling by pore
      condensation (axial-pore-filling mode) occurs at a low relative pressure,
      corresponding roughly to a single adsorbed monolayer. For SBA-15, owing to its
      larger pore diameter (8 nm), a gradual increase in the thickness of the adsorbed
      layer (radial-pore-filling mode) prevails until pore condensation takes place at
      a higher level of pore filling.

PMID- 15470693
TI  - The control of the cholesteric pitch by some azo photochemical chiral switches.
AB  - A few chiral azo compounds, which undergo reversible photochemical switching, are
      presented. Of these, the most interesting contain the binaphthyl moiety and
      belong to the C2 (derivatives 1 and 2) or C1 symmetry group (derivatives 3 and
      4). These binaphthyl compounds display intense CD and high beta values.
      Photochemical switching has profound effects on both the CD and beta values of
      these compounds; in the case of compound 3, the sign of beta changes upon
      isomerisation. Compound 2 has, to our knowledge, the highest beta of the switches
      reported in the literature and also seems the most interesting owing to its fast
      response to photochemical stimuli. Nematic phases can be transformed into
      cholesteric phases with reflection bands in the visible region by doping with
      reasonable amounts of 1 and 2. The reflection colours can be changed reversibly
      by photoisomerisation of the switches. Thermal reversion of the colourless UV
      photostationary state to the green isomeric EE state or to intermediate coloured
      states is temperature dependent. This can allow the thermal history of a sample
      to be traced.

PMID- 15470694
TI  - 2,5-Diphenyl-3,4-bis(2-pyridyl)cyclopenta-2,4-dien-1-one as a redox-active
      chelating ligand.
AB  - 2,5-Diphenyl-3,4-bis(2-pyridyl)cyclopenta-2,4-dien-1-one (1), a close relative of
      tetraphenylcyclopentadienone, is a new ligand platform for use in redox switches
      and sensors. Compound 1 acts as a molecular electrochemical sensor towards a
      range of divalent metal ions and exhibits favourable two-wave behaviour. It forms
      chelates of the type [(1)MX2], whose stability is enhanced by five orders of
      magnitude upon one-electron reduction. The bite angle of 1 is close to 90 degrees
      in these complexes. The attachment of the 14-valence-electron Cp*Co fragment to
      the cyclopentadienone pi system reduces the bite angle and thus modulates the
      binding characteristics of 1.

PMID- 15470695
TI  - New uses for the Burgess reagent in chemical synthesis: methods for the facile
      and stereoselective formation of sulfamidates, glycosylamines, and sulfamides.
AB  - Although the Burgess reagent (methoxycarbonylsulfamoyltriethylammonium hydroxide,
      inner salt) has found significant use in chemical synthesis as a dehydrating
      agent, almost no work has been directed towards its potential in other synthetic
      applications. As this article will detail, we have found that the Burgess reagent
      is remarkably effective at accomplishing a number of non-dehydrative synthetic
      tasks when applied to appropriate substrates, such as the formation of
      sulfamidates from 1,2-diols or epoxyalcohols, alpha- and beta-glycosylamines from
      carbohydrates, and cyclic sulfamides from 1,2-aminoalcohols. Beyond delineating
      the power of these new reaction manifolds, we also describe the construction of a
      group of alternative Burgess-type reagents that extends the scope of these new
      reactions even further.

PMID- 15470696
TI  - Rhodium-catalyzed intramolecular hydroacylation of 5- and 6-alkynals: convenient
      synthesis of alpha-alkylidenecycloalkanones and cycloalkenones.
AB  - A novel intramolecular hydroacylation of 5- and 6-alkynals leading to alpha
      alkylidenecycloalkanones was accomplished by using cationic a rhodium(I)/BINAP
      complex. For all cyclizations described, a single (E)-olefin isomer was obtained.
      At elevated temperature, hydroacylation and double bond migration of 5- and 6
      alkynals proceeded in a one-pot reaction to give cycloalkenones. An
      intramolecular hydroacylation of a 7-alkynal was unsuccessful. This method
      represents an attractive new route to highly functionalized alpha
      alkylidenecycloalkanones and cycloalkenones.

PMID- 15470697
TI  - Gas chromatography-tandem mass spectrometry analysis of gabapentin in serum.
AB  - A new highly sensitive analytical method for determining gabapentin [1
      (aminomethyl) cyclohexaneacetic acid; Neurontin] in serum using gas
      chromatography/tandem mass spectrometry (GC-MS/MS) was developed. GC-MS/MS was
      applied to determine the levels of gabapentin in serum samples of mice at 1 and 6
      h after oral or intraperitoneal treatment (300 mg/kg). At 1 h, the concentrations
      of the drug were 4.02 +/- 0.42 and 4.32 +/- 0.28 microg/mL in mice treated orally
      and intraperitoneally, respectively. At 6 h, drug levels decreased by about 66%
      in both groups. The method, coupling two stages of mass analysis, could be very
      useful in identifying the drug in complex mixtures such as blood and urine.
      Moreover, it is easy and rapid to perform, and sensitive enough to allow the
      presence of the drug to be determined at very low detection limits. It is a very
      reliable method for both clinical and experimental monitoring of gabapentin.

PMID- 15470698
TI  - The study of growth inhibitive protein factor by various mode of HPLC and
      estimation of its binding with drugs.
AB  - The protein fraction of the brain of white rat inhibiting the proliferation of
      homological cells was studied by hydrophobic interaction and reversed-phase
      liquid chromatography. The hybrid modification of hydrophobic interaction and
      biopartitional micellar chromatography was also applied for the elution of
      hydrophobic component of brain protein fraction. It was established that this
      protein fraction represents a hydrophilic-hydrophobic complex. The binding of
      pharmacological preparations with the brain protein fraction in the model system
      was also investigated. The separation of free and protein bound fractions of
      drugs was carried out by cloud-point extraction. It was shown that the degree of
      binding of phenobarbital with the mentioned protein fraction exceeds the same
      values for carbamazepine and chlorpromazine.

PMID- 15470699
TI  - Fragmentation patterns of selected ergot alkaloids by electrospray ionization
      tandem quadrupole mass spectrometry.
AB  - Tall fescue toxicosis and other maladies in livestock result from the ingestion
      of vasoconstrictive ergot alkaloids produced by fungal endophytes associated
      symbiotically with the grass. In order to facilitate future analyses of grass
      extracts considered responsible for outbreak of related livestock diseases, we
      examined the electrospray ionization mass spectra of specific ergot alkaloids
      under conditions that permit protonation. Our purposes were both to record the
      spectra with interpretation of mechanisms of fragmentation and to derive
      commonalities that would allow the prediction of mass spectra of related
      compounds for which standards were not readily available. With [M + H](+) values
      in parentheses, water-insoluble lysergic acid peptide ergot derivatives
      ergovaline (m/z 534), ergotamine (m/z 582), ergocornine (m/z 562), ergocryptine
      (m/z 576) and ergocrystine (m/z 610) exhibited a consistent loss of water (-18 u)
      from the C-12' alpha-hydroxy functionality. Of this group, ergovaline and
      ergotamine generated an m/z 320 fragment deriving from cleavage of ring E amide
      and ether functions with retention of the peptide ring system methyl group.
      Ergocornine, ergocryptine and ergocrystine similarly formed an m/z 348 fragment
      with retention of isopropyl. These assignments were supported by the lack of
      similar fragments from the water-soluble ergot ergonovine, which lacks a peptide
      ring system. Clavine-type ergot alkaloids lysergic acid and lysergol lack any
      substituents beyond simple ones directly on the C-8 position and, similarly to
      ergonovine, lack significant fragments at m/z 268, 251 and 225 shared by the
      peptide ergot alkaloids.

PMID- 15470700
TI  - Liquid chromatographic determination of nine N-methylcarbamates in drinking
      water.
AB  - A multi-residue method for the simultaneous extraction from drinking water using
      solid-phase extraction on LiChrolut EN [poly(styrene-divinylbenzene), PSDVB] and
      determination of nine N-methylcarbamate pesticides (NMCs) (aldicarb, its
      metabolites i.e. aldicarb sulfone and aldicarb sulfoxide and carbaryl,
      carbofuran, dioxacarb, ethiofencarb, methomyl and propoxur) using reversed-phase
      liquid chromatography was studied. A 1000-fold pre-concentration was achieved and
      the method was used for determination of the nine pesticides in water, with
      limits of detection in the range 3-15 ng L(-1). For all compounds the recoveries
      determined at the 0.1 and 1 microg L(-1) level generally ranged from 85 to 104%
      with relative standard deviations (RSD) of 1.4-8.8%.

PMID- 15470701
TI  - Determination of the sulphoxides and sulphones of three simple sulphides in rat
      urine: effects of phenobarbitone, beta-naphthoflavone and methimazole.
AB  - In this investigation, the measurement and identification of the S-oxidation
      products of three simple sulphides-ethyl methyl sulphide (EMS), 4-chlorophenyl
      methyl sulphide (CPMS) and diphenyl sulphide (DPS)-in rat urine were carried out
      and a study of the effects of phenobarbitone (PB), beta-naphtho flavone (betaNF)
      and methimazole on the urinary levels of their metabolites was conducted. Male
      Wistar rats (n = 4) were pretreated with PB (80 mg/kg/day in saline, i.p.),
      betaNF (100 mg/kg/day in corn oil, i.p.), methimazole (50 mg/kg/day in saline,
      i.p.) or the vehicles alone (1 mL/kg) for three consecutive days. After
      pretreatment, EMS, CPMS or DPS (50 mg/kg in corn oil, 500 microL) was
      administered orally to the appropriate groups of rats. The animals were placed in
      metabolic cages and urine samples collected at 24 h intervals over 96 h.
      Chromatographic and spectroscopic techniques were used for the measurement and
      identification of the sulphoxides and sulphones of EMS, CPMS and DPS in rat
      urine. Although only a trace of ethyl methyl sulphoxide (EMSO) was present in rat
      urine after administration of EMS, ethyl methyl sulphone (EMSO(2)) accounted for
      about 16% of the administered dose in the urine of male rats given EMS. In
      addition, pretreatment of rats with methimazole significantly decreased the S
      oxidation of EMS. 4-Chlorophenyl methyl sulphone (CPMSO(2)) was the main
      metabolite recovered in the urine of male rats treated with CPMS, accounting for
      about 10% of the dose. Pretreatment of rats with PB before administration of CPMS
      significantly increased the levels of CPMSO(2) excreted in the urine.
      Additionally, pretreatment of rats with methimazole significantly decreased the S
      oxidation of CPMS in vivo. About 2.5% of diphenyl sulphoxide (DPSO) and 4% of
      diphenyl sulphone (DPSO(2)) were recovered in the urine of male rats given DPS.
      Pretreatment of rats with PB, betaNF or methimazole before administration of DPS
      decreased the levels of DPSO and DPSO(2) excreted in the urine, although this was
      not statistically significant. These results indicate that microsomal
      monooxygenases mediate the S-oxidation of EMS, CPMS and DPS to their
      corresponding sulphones via a transient sulphoxide in rats.

PMID- 15470702
TI  - Synthesis of fluorescent label, DBD-beta-proline, and the resolution efficiency
      for chiral amines by reversed-phase chromatography.
AB  - DBD-d(and l)-beta-proline, new fluorescent chiral derivatization reagents, were
      synthesized from the reaction of 4-(N,N-dimethylaminosulfonyl)-7- fl uoro-2,1,3
      benzoxadiazole (DBD-F) with beta-proline. The racemic mixture synthesized was
      separated by a chiral stationary phase (CSP) column, Chiralpak AD-H, with n
      hexane-EtOH-TFA-diethylamine (70:30:0.1:0.1) as the mobile phase. The dl-forms
      were decided according to the results obtained from a circular dichroism (CD)
      detector after separation by the CSP column. The fractionated enantiomers reacted
      with chiral amine to produce a couple of diastereomers. The labeling proceeded in
      the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and pyridine
      as the activation reagents. The reaction conditions were mild and no racemization
      occurred during the diastereomer formation. The resulting diastereomers
      fluoresced at around 570 nm (excitation at around 460 nm). Good linearity of the
      calibration curves was obtained in the range 1-75 pmol and the detection limits
      on chromatogram were less than 1 pmol. The separability of the diastereomers was
      compared with the diastereomers derived from DBD-d(or l)-proline. The resolution
      values (Rs) obtained from the diastereomers of three chiral amines with DBD-d(or
      l)-beta-proline were higher than those derived from DBD-d(or l)-proline, e.g. dl
      phenylalanine methylester (dl-PAME), 2.23 vs 1.37; (R)(S)-1-phenylethylamine
      [(R)(S)-PEA], 2.09 vs 1.13; and (R)(S)-1-(1-naphthyl)ethylamines [(R)(S)-NEA],
      5.19 vs 1.23. The results suggest that the position of COOH group on pyrrolidine
      moiety in the structures is one of the important factors for the efficient
      separation of a couple of the diastereomers.

PMID- 15470703
TI  - Quantitative effects of thermal injury and insulin on the metabolism of the
      skeletal muscle using the perfused rat hindquarter preparation.
AB  - Injury from a severe burn or trauma can propel the body into a hypermetabolic
      state that can lead to the significant erosion of lean muscle mass.
      Investigations describing this process have been somewhat limited due to the lack
      of adequate experimental models. Here we report the use of a perfused rat
      hindquarter preparation to study the consequences of a moderate burn injury
      (approximately 20% total body surface area), with or without the addition of
      exogenous insulin (12.5 mU/mL), on the fluxes of major metabolites across the
      isolated skeletal muscle. The metabolic flux data was further analyzed using
      metabolic flux analysis (MFA), which allows for the estimation of the impact of
      these conditions on the intracellular muscle metabolism. Results indicate that
      this model is able to capture the increased rate of proteolysis, glutamine
      formation, and the negative nitrogen balance associated with the burn-induced
      hypermetabolic state. The inclusion of exogenous insulin resulted in significant
      changes in several fluxes, including an increase in the metabolism of glucose and
      the flux through the pentose phosphate pathway, as well as a reduction in the
      metabolism of glutamine, alanine, and leucine. However, insulin administration
      did not affect the nitrogen balance or the rate of proteolysis in the muscle, as
      has been suggested using other techniques. The use of the perfused hindquarter
      model coupled with MFA is a physiologically relevant and experimentally flexible
      platform for the exploration of skeletal muscle metabolism under catabolic
      conditions, and it will be useful in quantifying the specific metabolic
      consequences of other therapeutic advances.

PMID- 15470704
TI  - Differential gene expression shows natural brominated furanones interfere with
      the autoinducer-2 bacterial signaling system of Escherichia coli.
AB  - The quorum sensing disrupter (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)
      furanone (furanone) of the alga Delisea pulchra was previously found by us
      (Environ Microbiol 3:731-736, 2001) to inhibit quorum sensing in Escherichia coli
      via autoinducer-2 (AI-2, produced by LuxS). In this study, DNA microarrays were
      used to study the genetic basis of this natural furanone inhibition of AI-2
      signaling (significant values with p < 0.05 are reported). Using DNA microarrays,
      the AI-2 mutant Escherichia coli DH5alpha was compared with the AI-2 wild-type
      strain, E. coli K12, to determine how AI-2 influenced gene expression.
      Escherichia coli K12 was also grown with 0 and 60 microg/mL furanone to study the
      inhibition of quorum sensing gene expression. It was found that 166 genes were
      differentially expressed by AI-2 (67 were induced and 99 were repressed) and 90
      genes were differentially expressed by furanone (34 were induced and 56 were
      repressed). Importantly, 79% (44 out of 56) of the genes repressed by furanone
      were induced by AI-2, which indicated that furanone inhibited AI-2 signaling and
      influenced the same suite of genes as a regulon. Most of these genes have
      functions of chemotaxis, motility, and flagellar synthesis. Interestingly, the
      aerotaxis genes aer and tsr were discovered to be induced by AI-2 and repressed
      by furanone. Representative microarray results were confirmed by RNA dot
      blotting. Furthermore, the E. coli air-liquid interface biofilm formation was
      repressed by furanone, supporting the results that taxis and flagellar genes were
      repressed by furanone. The autoinducer bioassay indicated that 100 microg/mL
      furanone decreased the extracellular concentration of AI-2 2-fold, yet luxS and
      pfs transcription were not significantly altered. Hence, furanone appeared to
      alter AI-2 signaling post-transcriptionally.

PMID- 15470705
TI  - A method for the determination of flux in elementary modes, and its application
      to Lactobacillus rhamnosus.
AB  - In this article we address the question of how, given information about the
      reaction fluxes of a system, flux values can be assigned to the elementary modes
      of that system. Having described a method by which this may be accomplished, we
      first illustrate its application to a hypothetical, in silico system, and then
      apply it to fermentation data from Lactobacillus rhamnosus. This reveals
      substantial changes in the flux values assigned to elementary modes, and thus to
      the internal metabolism, as the fermentation progresses. This is information that
      could not, to our knowledge, be obtained by existing methods. The relationship
      between our technique and the well-known method of Metabolic Flux Analysis is
      also discussed.

PMID- 15470706
TI  - Mechanism of extraction of beta-carotene from microalga Dunaliellea salina in two
      phase bioreactors.
AB  - We show that it is possible to extract beta-carotene selectively from Dunaliella
      salina in two-phase bioreactors. The cells continue to produce beta-carotene and
      the extracted part is substituted by newly produced molecules. This process is
      called "milking." We performed several experiments to understand the exact
      mechanism of the extraction process. The results show that direct contact between
      the cells and the biocompatible organic solvent was not a requirement for the
      extraction but it accelerated the extraction. Electron microscopy photographs
      showed an undulated shape of the cell membrane and a space between the cell and
      the chloroplast membranes in the cells growing in the presence of dodecane (a
      biocompatible solvent). Extra-chloroplast beta-carotene globules located in the
      space between the cell and the chloroplast membranes were observed in these cells
      as well. It was shown that dodecane was taken up by the cells. The concentration
      of dodecane in the cells was about 13 pg.cll(-1). It can be concluded that
      dodecane uptake by the cells is responsible for the morphological changes in the
      cells and leads to more activity in the cell membrane. The results suggest two
      possible modes of extraction. One of the mechanisms is transport of the globules
      from the chloroplast to the space between the cell and the chloroplast membranes
      and subsequently from there to the outside by exocytosis. Another possible mode
      for the extraction could be release of beta-carotene from the globules as a
      result of alterations in the membrane in response to the uptake of dodecane. beta
      Carotene molecules diffuse from the chloroplast to the space between the cell and
      the chloroplast membranes and from there to the medium either by diffusion or by
      exocytosis after accumulation in the vesicles.

PMID- 15470707
TI  - Volumetric measurements of bacterial cells and extracellular polymeric substance
      glycoconjugates in biofilms.
AB  - In this study an enrichment culture developed from activated sludge was used to
      investigate the architecture of fully hydrated multispecies biofilms. The
      assessment of biofilm structure and volume was carried out using confocal laser
      scanning microscopy (CLSM). Bacterial cell distribution was determined with the
      nucleic acid-specific stain SYTO 60, whereas glycoconjugates of extracellular
      polymeric substances (EPS) were stained with the Alexa-488-labeled lectin of
      Aleuria aurantia. Digital image analysis was employed for visualization and
      quantification of three-dimensional CLSM data sets. The specific volumes of the
      polymeric and cellular biofilm constituents were quantified. In addition,
      gravimetric measurements were done to determine dry mass and thickness of the
      biofilms. The data recorded by the CLSM technique and the gravimetric data were
      then compared. It was shown that the biofilm thicknesses determined with both
      methods agree well for slow-growing heterotrophic and chemoautotrophic biofilms.
      In addition, for slow-growing biofilms, the volumes and masses calculated from
      CLSM and the biomass calculated from gravimetric measurements were also
      comparable. For fast-growing heterotrophic biofilms cultivated with high glucose
      concentrations the data sets fit to a lesser degree, but still showed the same
      common trend. Compared with traditional gravimetric measurements, CLSM allowed
      differential recording of multiple biofilm parameters with subsequent three
      dimensional visualization and quantification. The quantitative three-dimensional
      results recorded by CLSM are an important basis for understanding, controlling,
      exploiting, and modeling of biofilms.

PMID- 15470708
TI  - A renal mass in the setting of a nonrenal malignancy: When is a renal tumor
      biopsy appropriate?
AB  - BACKGROUND: Frequently, a renal mass is identified when patients with cancer
      undergo studies for staging or surveillance. In determining whether it represents
      a metastasis, patients are frequently subjected to percutaneous renal biopsies.
      The authors evaluated their experience with this dilemma to formulate management
      guidelines. METHODS: The authors reviewed the medical records of 100 consecutive
      patients with nonrenal malignancies diagnosed with renal masses at presentation
      or follow-up. Renal mass histology was available for all patients after
      nephrectomy or biopsy. Clinical characteristics were assessed to identify factors
      predictive for a renal metastasis versus a primary renal neoplasm. RESULTS: The
      only factors predictive of a metastasis to the kidney were progression of the
      nonrenal malignancy and lack of enhancement of the renal mass (P < 0.0001). Forty
      six patients (46%) had evidence of progression of their nonrenal malignancy in
      addition to the renal mass. In these patients, the probability of a metastasis to
      the kidney was 86% (95% confidence interval [CI], 57.2-98.2%) without renal mass
      enhancement and 32% (95% CI, 14-55%) with enhancing renal masses. None of the 54
      patients without signs of progression of their nonrenal malignancy proved to have
      metastases to the kidney, regardless of the imaging characteristics of the mass
      (zero probability; 95% CI, 0-7%; P < 0.001). CONCLUSIONS: In patients presenting
      with renal masses and another clinically localized malignancy, renal mass
      biopsies were not indicated, as the mass rarely represented a metastasis. These
      patients may opt for close surveillance or extirpation based on the prognosis of
      their nonrenal malignancy.

PMID- 15470709
TI  - Robust control of initiation of prokaryotic chromosome replication: essential
      considerations for a minimal cell.
AB  - A genomically and chemically detailed mathematical model of a "minimal cell"
      would be useful to understand better the "design logic" of cellular regulation. A
      "minimal cell" will be a prokaryote with the minimum number of genes necessary
      for growth and replication in an ideal environment (i.e., preformed precursors,
      constant temperature, etc.). The Cornell single-cell model of Escherichia coli
      serves as the basic framework upon which a minimal cell model can be constructed.
      A critical issue for any cell model is to describe a mechanism for control of
      initiation of chromosome replication. There is strong evidence that the essence
      of chromosome replication control is highly conserved in eubacteria and even
      extends to the archae. A generalized mechanism is possible based on binding of
      the protein DnaA-ATP to the origin of replication (oriC) as a primary control.
      Other features, such as regulatory inactivation of DnaA (RIDA) by conversion of
      DnaA-ATP to DnaA-ADP and titration of DnaA by binding to other DnaA boxes on the
      chromosome, have emerged as critical elements in obtaining a functional system to
      control initiation of chromosome synthesis. We describe a biologically realistic
      model of chromosome replication initiation control embedded in a complete whole
      cell model that explicitly links the external environment to the mechanism of
      replication control. The base model is deterministic and then modified to include
      stochastic variation in the components for replication control. The stochastic
      model allows evaluation of the model's robustness, employing a low standard
      deviation of interinitiation time as a measure of robustness. Four factors were
      examined: DnaA synthesis rate; DnaA-ATP binding sites at oriC; the binding rate
      of DnaA-ATP to the nonfunctional DnaA boxes; and the effect of changing the
      number of nonfunctional binding sites. The observed DnaA synthesis rate (2000
      molecules/cell) and the number of DnaA binding sites per origin (30) are close to
      the values predicted by the model to provide good control (low variance of
      interinitiation time), with a reasonable expenditure of cell resources. At
      relatively high binding rates for DnaA-ATP to the DnaA boxes (10(16) M(-1) s(
      1)), increasing the number of DnaA binding sites to about 300, improved control
      (but little further improvement was seen by extension to 1000 boxes); however, at
      a low binding rate (10(10) M(-1) s(-1)), an increase in DnaA boxes had an adverse
      effect on control. The combination of all four factors is probably necessary to
      obtain a robust control system. Although this mechanism of replication initiation
      control is highly conserved, it is not clear if simpler control in a minimal cell
      might exist based on experimental observations with Mycoplasma. This issue is
      discussed in this investigation.

PMID- 15470710
TI  - Small cell astrocytoma: an aggressive variant that is clinicopathologically and
      genetically distinct from anaplastic oligodendroglioma.
AB  - BACKGROUND: Small cell glioblastoma (GBM) is a variant with monomorphous,
      deceptively bland nuclei that often is misdiagnosed as anaplastic
      oligodendroglioma. METHODS: To elucidate its clinicopathologic and genetic
      features, the authors studied 71 adult patients (median age, 57 years), including
      22 patients who were identified from a set of 229 GBMs (10%) that had been
      characterized previously by epidermal growth factor receptor (EGFR)/EGFR-vIII
      variant immunohistochemistry. Tumors also were analyzed by fluorescence in situ
      hybridization for 1p, 19q, 10q, and EGFR copy numbers. RESULTS: Radiologically,
      37% of tumors that were not selected for grade showed minimal to no enhancement.
      Similarly, 33% of tumors had no endothelial hyperplasia or necrosis
      histologically, qualifying only as anaplastic astrocytoma (Grade III) using World
      Health Organization criteria. Nevertheless, such tumors progressed rapidly, with
      mortality rates that were indistinguishable from their Grade IV counterparts. The
      median survival for 37 patients who were followed until death was 11 months.
      Oligodendroglioma-like histology included chicken-wire vasculature (86%), haloes
      (73%), perineuronal satellitosis (58%), and microcalcifications (45%), although
      mucin-filled microcystic spaces were lacking. No small cell astrocytomas had
      1p/19q codeletions, whereas EGFR amplification and 10q deletions were present in
      69% and 97% of small cell astrocytomas, respectively. The tumors expressed EGFR
      and EGFR-vIII more commonly than nonsmall cell GBMs (83% vs. 35% [P < 0.001]; 50%
      vs. 21% [P < 0.001] respectively). CONCLUSIONS: Small cell astrocytoma is an
      aggressive histologic variant that behaved like primary GBM, even in the absence
      of endothelial hyperplasia and necrosis. Despite considerable morphologic overlap
      with anaplastic oligodendroglioma, clinicopathologic and genetic features were
      distinct. Fifty percent of small cell astrocytomas expressed the constitutively
      activated vIII mutant form of EGFR, and molecular testing for 10q deletion
      improved the diagnostic sensitivity over EGFR alone.

PMID- 15470711
TI  - Pioglitazone and rofecoxib combined with angiostatically scheduled trofosfamide
      in the treatment of far-advanced melanoma and soft tissue sarcoma.
AB  - BACKGROUND: Combined treatment approaches targeting tumor cells as well as
      stromal cells may control chemorefractory malignancies. In the current study, the
      authors sought to test one such combined approach in the treatment of
      chemorefractory melanoma and soft tissue sarcoma. METHODS: A Phase II trial was
      initiated to analyze the activity of a continuously administered molecularly
      targeted treatment regimen (daily pioglitazone [45 mg administered orally] and
      rofecoxib [25 mg administered orally]) combined with sequentially added
      angiostatic chemotherapy for patients with previously treated metastatic melanoma
      (n = 19) or soft tissue sarcoma (n = 21). Angiostatic chemotherapy consisted of
      trofosfamide (50 mg) administered orally 3 times daily beginning on the 15th day
      after the start of molecularly targeted therapy. RESULTS: Forty patients were
      evaluable for response and toxicity. Major side effects (World Health
      Organization Grade 3 or 4) were not observed. Objective responses and disease
      stabilization lasting longer than 6 months were noted in 11% and 11%,
      respectively, of all patients with melanoma and in 19% and 14%, respectively, of
      all patients with soft tissue sarcoma. Complete remission was noted in one
      patient with melanoma and in three patients with sarcoma. Both normal C-reactive
      protein (CRP) levels and CRP levels that decreased by > 30% during the 14-day
      biomodulator pretreatment period were found to be predictive of prolonged
      progression-free survival. CONCLUSIONS: To our knowledge, the current study is
      the first to demonstrate that a novel, completely orally administered combined
      biomodulator/metronomic chemotherapy regimen may be active and well tolerated in
      patients with chemorefractory malignancies.

PMID- 15470712
TI  - Effects of cancer history and comorbid conditions on mortality and healthcare use
      among older cancer survivors.
AB  - BACKGROUND: Older cancer survivors use healthcare services to an increased extent
      relative to their counterparts who have no history of malignant disease. In the
      current study, the authors set out to assess the effects of cancer history and
      comorbid conditions on healthcare use and mortality. METHODS: Using information
      from the 1992 North Carolina Established Populations for Epidemiologic Study of
      the Elderly database, study participants were classified as having no history of
      malignant disease or as having a recent (cancer diagnosed < 1 year earlier),
      intermediate (cancer diagnosed 1-6 years earlier), or remote (cancer diagnosed >
      6 years earlier) history of malignancy. Overall, 15 different comorbid conditions
      were ascertained. Logistic regression models adjusted for sociodemographic
      factors, tobacco and alcohol use, and functional measures were used to determine
      the risk of emergency room, hospital, and nursing home (NH) admission in 1992 and
      also in 1996 according to history of malignancy and presence of comorbid
      conditions. Using data from the National Death Registry, a similar controlled
      analysis of 7-year mortality also was performed. RESULTS: There were 2567
      participants in the current study (mean age, 79 years; range, 71-102 years); 69%
      of all participants were women, 55% were African American, and 14% reported
      having a history of malignancy. Participants with a history of malignancy had an
      average of 3 comorbid conditions, and differences across groups in terms of
      cardiovascular and lung disease incidence were noted. Controlled analyses
      revealed that recent cancer history (odds ratio [OR], 15.5; 95% confidence
      interval [CI], 7.0-34.2) and intermediate cancer history (OR, 2.1; 95% CI, 1.4
      3.3) were associated with same-year hospital admission. In addition, having a
      recent history of malignancy in 1992 was found to be correlated with NH admission
      4 years later (OR, 3.1; 95% CI, 1.1-9.1). History of malignancy was not
      associated with mortality. CONCLUSIONS: Cancer history had limited influence on
      healthcare use and mortality. Efforts aimed at improving health-related outcomes
      in older cancer survivors should continue to focus on attenuating the impact of
      comorbid conditions.

PMID- 15470713
TI  - The prevention of invasive breast carcinoma.

PMID- 15470714
TI  - High solid simultaneous saccharification and fermentation of wet oxidized corn
      stover to ethanol.
AB  - In this study ethanol was produced from corn stover pretreated by alkaline and
      acidic wet oxidation (WO) (195 degrees C, 15 min, 12 bar oxygen) followed by
      nonisothermal simultaneous saccharification and fermentation (SSF). In the first
      step of the SSF, small amounts of cellulases were added at 50 degrees C, the
      optimal temperature of enzymes, in order to obtain better mixing condition due to
      some liquefaction. In the second step more cellulases were added in combination
      with dried baker's yeast (Saccharomyces cerevisiae) at 30 degrees C. The phenols
      (0.4-0.5 g/L) and carboxylic acids (4.6-5.9 g/L) were present in the
      hemicellulose rich hydrolyzate at subinhibitory levels, thus no detoxification
      was needed prior to SSF of the whole slurry. Based on the cellulose available in
      the WO corn stover 83% of the theoretical ethanol yield was obtained under
      optimized SSF conditions. This was achieved with a substrate concentration of 12%
      dry matter (DM) acidic WO corn stover at 30 FPU/g DM (43.5 FPU/g cellulose)
      enzyme loading. Even with 20 and 15 FPU/g DM (corresponding to 29 and 22 FPU/g
      cellulose) enzyme loading, ethanol yields of 76 and 73%, respectively, were
      obtained. After 120 h of SSF the highest ethanol concentration of 52 g/L (6
      vol.%) was achieved, which exceeds the technical and economical limit of the
      industrial-scale alcohol distillation. The SSF results showed that the cellulose
      in pretreated corn stover can be efficiently fermented to ethanol with up to 15%
      DM concentration. A further increase of substrate concentration reduced the
      ethanol yield significant as a result of insufficient mass transfer. It was also
      shown that the fermentation could be followed with an easy monitoring system
      based on the weight loss of the produced CO2.

PMID- 15470715
TI  - Mortality associated with daily bolus 5-fluorouracil/leucovorin administered in
      combination with either irinotecan or oxaliplatin: results from Intergroup Trial
      N9741.
AB  - BACKGROUND: Intergroup Trial N9741 evaluated 5-fluorouracil (5-FU)/leucovorin
      (LV) administered in conjunction with either irinotecan or oxaliplatin in the
      first-line treatment of advanced colorectal carcinoma (CRC). The current report
      describes two treatment arms that were withdrawn from the protocol due to
      unexpected treatment-related toxicities and a high mortality rate. The
      complications observed in these arms highlight the importance of aggressive and
      immediate supportive care in the management of digestive toxicity. METHODS: In
      Trial N9741, patients were randomly assigned to receive one of the following six
      regimens: 1) irinotecan plus bolus 5-FU/LV (Arm A); 2) sequential irinotecan plus
      bolus 5-FU/LV (Arm B); 3) bolus 5-FU/LV only (Mayo Clinic regimen; Arm D); 4)
      oxaliplatin plus bolus 5-FU/LV (Arm E); 5) oxaliplatin plus infusional 5-FU/LV
      (Arm F); or 6) oxaliplatin plus irinotecan (Arm G). In the current study, the
      authors investigated treatment-related toxicity in patients who received either
      of the two combination regimens containing daily bolus 5-FU (i.e., patients in
      Arm B or Arm E). RESULTS: Sixty-one and 47 patients were enrolled in Arm B and
      Arm E, respectively. Diarrhea and neutropenia were the most common toxicities in
      both groups. Five patients in Arm B (8.2%) and 4 patients in Arm E (8.5%) died
      within 60 days of study entry. All fatal toxicities occurred within 15 days of
      treatment administration, and all deaths were associated with the simultaneous
      occurrence of multiple symptoms, which were dominated by Grade > or = 3 diarrhea.
      CONCLUSIONS: Combination regimens containing daily bolus 5-FU/LV and oxaliplatin
      or irinotecan can be associated with severe gastrointestinal toxicity and high
      mortality rates. Therefore, the authors recommend the use of more tolerable
      infusional 5-FU-based regimens in the treatment of metastatic CRC.

PMID- 15470716
TI  - Analytical monitoring of alcoholic fermentation using NIR spectroscopy.
AB  - Alcoholic fermentation under Saccharomyces cerevisiae yeasts is governed largely
      by glucose uptake, biomass formation, ethanol and glycerin production, and
      acidification. In this work, PLS calibration models were developed with a view to
      determining these analytical parameters from near infrared spectra and analytical
      data provided by the corresponding reference methods. The models were applied to
      a set of samples obtained from various fermentation processes. The glucose,
      ethanol, and biomass values predicted by the models exhibited a high correlation
      with those provided by the reference method.

PMID- 15470717
TI  - Parameter oscillations in a very high gravity medium continuous ethanol
      fermentation and their attenuation on a multistage packed column bioreactor
      system.
AB  - The quasi-steady-states, marked by small fluctuations of residual glucose,
      ethanol, and biomass concentrations, and sustainable oscillations marked by big
      fluctuations of these monitored fermentation parameters were observed during the
      continuous ethanol fermentation of Saccharomyces cerevisiae when very high
      gravity media were fed and correspondingly high ethanol concentrations reached. A
      high ethanol concentration was shown to be one of the main factors that incited
      these oscillations, although the residual glucose level affected the patterns of
      these oscillations to some extent. The lag response of S. cerevisiae to high
      ethanol stress that causes the shifts of morphology, viability loss, and death of
      yeast cells is assumed to be one of the probable mechanisms behind these
      oscillations. It was predicted that the longer the delay of this response was,
      the longer the oscillation periods would be, which was validated by the
      experimental data and the comparison with the oscillatory behaviors reported for
      the ethanologen bacterium, Zymomonas mobilis. Furthermore, three tubular
      bioreactors in series were arranged to follow a stirred tank bioreactor to
      attenuate these oscillations. However, exaggerated oscillations were observed for
      the residual glucose, ethanol, and biomass concentrations measured in the broth
      from these tubular bioreactors. After the tubular reactors were packed with
      Intalox ceramic saddle packing, these oscillations were effectively attenuated
      and quasi-steady-states were observed during which there were very small
      fluctuations of residual glucose, ethanol, and biomass within the entire
      experimental run.

PMID- 15470719
TI  - Acitretin embryopathy: a case report.
AB  - BACKGROUND: Acitretin is an aromatic retinoid analog of vitamin A. Drugs of this
      group are well-known teratogenic agents. Nevertheless, acitretin embryopathy has
      been described only in fetuses. CASE: An infant was exposed to 10 mg/day of
      acitretin from the beginning of pregnancy until the 10th gestational week. At
      term, the newborn showed the following abnormalities: microcephaly, epicanthal
      folds, low nasal bridge, high palate, cup-shaped ears, anteverted nostrils,
      atrial septal defect, and bilateral sensorineural deafness. At 18 months of age,
      the patient showed microcephaly and neurodevelopmental delay. CONCLUSIONS: Our
      patient shows a pattern of anomalies resembling that observed in isotretinoin-
      and etretinate-exposed children. After ingestion, acitretin is partially
      converted into etretinate, and etretinate is partially metabolized into
      acitretin. A similar phenotype would therefore be expected after prenatal
      exposure to either drug. Moreover, in the present case, teratogenic effects were
      observed even though the dose was lower than in the previously reported acitretin
      embryopathy cases. Therefore, we propose that different retinoids, acitretin
      included, produce only one malformation pattern with variable phenotypic
      expression.

PMID- 15470720
TI  - Regulated expression of VP16CREB in neuroblastoma cells: analysis of
      differentiation and apoptosis.
AB  - Highly malignant neuroblastoma tumors generally have defects in differentiation
      and apoptotic pathways. For a better understanding of these events, we use a
      murine neuroblastoma cell line (NBP2) that terminally differentiates into mature
      neurons in response to elevated levels of cAMP. Because one of the main
      downstream effectors of the cAMP signaling pathway is cAMP-response element
      binding (CREB), we reasoned that it might affect the expression of genes
      associated with differentiation and apoptotic events in NBP2 cells. To
      investigate this, we established tetracycline-regulated expression (TetOff) of
      VP16CREB, which constitutively transactivates promoters containing the CRE
      sequence motif. Using this system, we found that inducible expression of VP16CREB
      in NBP2 cells results in 1) morphological differentiation that is characterized
      by the formation of neurites and growth cones, 2) reversible cell differentiation
      unlike cAMP-induced terminal differentiation, 3) cell cycle arrest at G1, 4) no
      apoptosis in the presence of partial inhibition of proteasome unlike an increase
      in cAMP levels, and 5) changes in the expression of many genes, including down
      regulation of N-myc, cyclin B1, Dickkopf-1, and Mad-2 and up-regulation of
      tyrosine hydroxylase, c-fos, N10, and ICER genes. Although VP16CREB expression
      and activation of the cAMP pathway impart many similar effects in NBP2 cells,
      they also bear some distinct genetic and morphological differences. Our data
      suggest that increased levels of cAMP function through not only CREB but also
      other signaling pathways that account for the additional cAMP-induced effects,
      including irreversible differentiation and onset of apoptosis during partial
      inhibition of proteasome in NBP2 cells.

PMID- 15470721
TI  - Cyclosilicate nanocomposite: a novel resorbable bioactive tissue engineering
      scaffold for BMP and bone-marrow cell delivery.
AB  - Porous bioactive resorbable silica-calcium phosphate nanocomposite (SCPC) was
      prepared by a sintering technique. XRD analyses showed that the main crystalline
      phases of the SCPC are Na(3)CaPSiO(7) (clinophosinaite), beta-NaCaPO(4)
      (rhenanite), Na(2)CaSiO(4), and beta-quartz (SiO(2)). The clinophosinaite is a
      novel cyclosilicate bioactive mineral that enhanced the mechanical and
      bioactivity properties of the SCPC. TEM analysis showed that the grain sizes of
      the multiphase SCPC are in the nanometer scale. Moreover, the SCPC was engineered
      with nano- and microscale porosity. The SCPC had significantly higher compressive
      strength than porous hydroxyapatite (HA). FTIR analyses revealed the formation of
      biological hydroxyapatite layer on the SCPC surface after 4 days of immersion in
      SBF. When SCPC was loaded with rhBMP-2, it provided a superior release profile of
      biologically active rhBMP-2 compared to porous HA. Bone-marrow cells incubated
      with medium treated with the rhBMP-2 released from the SCPC-rhBMP-2 hybrid
      expressed significantly higher alkaline phosphatase activity than that expressed
      by cells incubated with media treated with rhBMP-2 released from HA-rhBMP-2. In
      addition, cells attached to the SCPC-rhBMP-2 hybrid produced mineralized
      extracellular matrix (ECM) and bone-like tissue that covered the material surface
      and filled pores in the entire thickness of the template after 3 weeks in
      culture. In contrary, cells attached to the HA-rhBMP-2 produced limited amount of
      unmineralized ECM after the same time period. Results of the study strongly
      suggest that the porous bioactive silica-calcium phosphate nanocomposite can
      serve as a delivery system for cells and biological molecules. The SCPC-rhBMP-2
      marrow cell hybrid may serve as an alternative to autologous bone grafting.

PMID- 15470722
TI  - Ageing-related decline in adenosine A1 receptor binding in the rat brain: an
      autoradiographic study.
AB  - The adenosine system has important neuromodulatory and neuroprotective functions
      in the brain. Several lines of evidence suggest that ageing is associated with
      major alterations in the adenosine system, which may be partially responsible for
      changes in sleep, mood, and cognition. In the present study, we examined
      adenosine A1 receptor density in the rat brain by means of quantitative
      autoradiography to obtain a detailed anatomical overview of the changes during
      ageing. A1 receptor binding was assessed in young, old, and senescent animals of
      3, 24, and 30 months old, respectively. There was a clear age-dependent reduction
      in adenosine A1 receptors in most of the brain areas examined, but the magnitude
      of this reduction varied greatly among regions. Also, whereas some regions
      displayed a gradual decline in A1 binding sites across the three age classes,
      other regions showed a particularly strong decrease between the ages of 24 and 30
      months. For example, whereas the hippocampus and thalamus showed a gradual
      decline in A1 binding, some cortical and septal regions showed a more abrupt
      decline after the age of 24 months. Since particularly in rats many studies have
      used animals at the age of 24 months or even less, the ageing-related decline in
      adenosine A1 signaling might have been underestimated.

PMID- 15470723
TI  - Cholinergic synaptic signaling mechanisms underlying behavioral teratogenicity:
      effects of nicotine, chlorpyrifos, and heroin converge on protein kinase C
      translocation in the intermedial part of the hyperstriatum ventrale and on
      imprinting behavior in an avian model.
AB  - A wide variety of otherwise unrelated neuroteratogens elicit a common set of
      behavioral defects centering around cholinergic contributions to cognitive
      function. We utilized the developing chick to overcome confounds related to
      maternal effects and compared the actions of nicotine, chlorpyrifos, and heroin
      on cholinergic signaling in the intermedial part of the hyperstriatum ventrale
      (IMHV), which controls imprinting behavior. Chicken eggs were injected with
      nicotine (10 mg/kg of egg), chlorpyrifos (10 mg/kg of egg), or heroin (20 mg/kg
      of egg; all doses below the threshold for dysmorphology) on incubation days (ID)
      0 and 5, and then tests were conducted posthatching. All three compounds elicited
      significant deficits in imprinting behavior. We also found defects in cholinergic
      synaptic signaling specifically involving the muscarinic receptor-mediated
      membrane translocation of protein kinase C (PKC)-gamma and in the basal levels of
      both PKCgamma and PKCbetaII, the two isoforms known to be relevant to behavioral
      performance. In contrast, there were no alterations in the response of PKCalpha,
      an isoform that does not contribute to the behavior, nor were cytosolic levels of
      any of the isoforms affected. Taken together with similar results obtained in
      rodents, our findings suggest that disparate neuroteratogens all involve
      signaling defects centering on the ability of cholinergic receptors to elicit
      PKCgamma translocation/activation and that this effect is direct, i.e., not
      mediated by maternal confounds. The chick thus provides a suitable model for the
      rapid screening of neuroteratogens and elucidation of the mechanisms underlying
      behavioral anomalies.

PMID- 15470724
TI  - The unification of psychology: a noble quest.
AB  - Henriques' effort to develop a unified theory for psychology represents a noble
      quest (this issue). Even if the quest fails, the effort itself may produce
      benefits for psychology. This article focuses first on some general comments on
      the unified theory, with some suggestions about elements that seem desirable in
      the theory and some elements that may benefit from further elaboration. A
      specific application to the area of posttraumatic growth suggests the theory is
      capable of providing a framework for understanding specific areas of human
      psychology. Finally, the potential future of the unified theory is considered
      with a focus on its potential as a "useful mass movement" in psychology.

PMID- 15470725
TI  - How does psychotherapy influence personality? A theoretical integration.
AB  - A given type of psychotherapy (e.g., psychodynamic) is associated with a set of
      specific change techniques (e.g., interpreting defenses, identifying relationship
      themes). Different change techniques can be conceived of as influencing different
      parts of personality (e.g., interpreting defense increases conscious awareness).
      An integrated model of personality is presented. Then, change techniques from
      different theoretical perspectives are assigned by judges to areas of personality
      the techniques are believed to influence. The results suggest that specific
      change techniques can be reliably sorted into the areas of personality. Thinking
      across theoretical perspectives leads to important new opportunities for
      assessment, therapy outcome research, and communication with patients concerning
      personality change.

PMID- 15470726
TI  - Beyond the justification hypothesis: a broader theory of the evolution of self
      consciousness.
AB  - We evaluate Henriques' Justification Hypothesis (JH; this issue) and argue that
      his explanation for the evolution of self-consciousness is overly narrow and the
      evolutionary sequence of events is backwards. Instead, we propose a broader
      theory of the evolution of self-consciousness, with four categories of adaptive
      functions: (a) self-regulation, (b) selective information processing, (c)
      understanding others, and (d) identity formation.

PMID- 15470727
TI  - Pluralism in the sciences is not easily dismissed.
AB  - The unification scheme proposed by Henriques in his article "Psychology Defined"
      (this issue) holds promise as a coherent and comprehensive approach to psychology
      and as a helpful way to think about the relation of psychology to other sciences.
      There is, nevertheless, room for concern that there is no concept of unification
      to date that does not neglect important dimensions of human experience. It is
      argued that the disunities in psychology need not result in a sense of
      disciplinary inferiority. In fact, many leading scholars now challenge the belief
      that other sciences are models of integration and unity. It is also argued that
      there are not true type identities between levels of organization (e.g.,
      experience and underlying neurological processes). Accordingly, there are serious
      questions about the kind of unity that can be achieved.

PMID- 15470728
TI  - Metarepresentation and the great cognitive divide: a commentary on Henriques'
      "psychology defined".
AB  - I locate the discontinuity between humans and other animals a bit differently
      than Henriques (this issue)-in metarepresentational abilities. However, I do
      think that the justification process might have played a critical role in the
      development of these metarepresentational abilities.

PMID- 15470729
TI  - The unification of psychology and psychological organizations.
AB  - The Tree of Knowledge is an imaginative attempt to construct a metatheoretical
      system that proposes to unify the discipline of psychology. However, it is
      limited in its appreciation of political factors, and so an optimistic view of
      the possibility of the system overlooks the power issues that beset the field.

PMID- 15470730
TI  - Rooting the tree of knowledge: a response to Henriques' "psychology defined".
AB  - Neither science nor culture could exist without a participant-observer and a
      conceiving human mind. Being-in-the-world, or "Dasein," as Heidegger termed it,
      is fundamental to any conceptual understanding we have of how things work in the
      universe. There is no view from nowhere. Psychology is the primordial ground in
      which the tree of knowledge has its roots.

PMID- 15470731
TI  - Unifying psychology: epistemological act or disciplinary maneuver?
AB  - Two arguments with attempts to unify psychology are adumbrated in this
      commentary. First, the unification of psychology is largely a disciplinary
      maneuver and not primarily an epistemological act. Second, the discipline of
      psychology has been unified for some time around a series of methodological and
      functional categories that have served to support its institutional projects but
      hide metaphysical problems.

PMID- 15470732
TI  - Unity within psychology, and unity between science and practice.
AB  - The unity of psychology as a science is to be found in its definition as the
      science of mental life, and its explanation of individual behavior in terms of
      mental states. This disciplinary focus will help negotiate psychology's relations
      with other disciplines, such as neuroscience and cognitive science. The unity
      within psychology between science and practice is to be found in a focus on
      scientific evidence as the source of the status, autonomy, and privileges of
      professional practitioners. Psychology should avoid the temptations of
      reductionism, and assert (and enjoy) its twin status as both a biological science
      and a social science.

PMID- 15470733
TI  - Defining psychology: is it worth the trouble?
AB  - Henrique's thoughtful effort (this issue) to define psychology suffers from at
      least three shortcomings: (a) "psychology" is almost certainly an inherently
      fuzzy concept that resists precise definition; (b) attempts to define psychology
      are likely to hamper rather than foster consilience across scientific
      disciplines; and (c) Henriques incorrectly diagnoses the cause of the scientist
      practitioner gap and hence offers an incorrect prescription. The sources of this
      gap lie not in intractable definitional disputes, but in fundamentally different
      approaches to acquiring knowledge.

PMID- 15470734
TI  - Taxonomy as a contextualist views it.
AB  - The Henriques' article, "Psychology Defined" (this issue), reflects an underlying
      philosophy of science that emphasizes coherence as its truth criterion. The
      taxonomic efforts that result are of unknown value when viewed from other
      philosophical positions. From the point of view of functional contextualism, the
      primary metric of successful science is not coherence per se, but the precision,
      scope, and depth of the analysis as a means of predicting and influencing
      psychological phenomena. Henriques presents neither data nor specific research
      proposals that would allow even the beginning application of such a metric. Thus,
      the proposed taxonomy has no known value when viewed contextualistically. Since
      the practical goals of clinical psychology are very similar to those of
      functional contextualism, clinical psychologists interested in making a practical
      difference will have few current empirical reasons to be attracted to this
      taxonomy.

PMID- 15470735
TI  - Psychology's dilemma: an institutional neurosis?
AB  - The term psychology refers both to an institutional discipline and to a subject
      matter. Henriques, in his article "Psychology Defined" (this issue) , emphasizes
      the second reference, and its focus can be sharpened by taking into account the
      first reference. On the one hand, epistemic progress in science is a dynamic
      process, which, as often as not, cuts across institutional divisions. However, on
      the other hand there are some problems of disunity that solely concern the
      institution. That the latter falls within the scope of the Tree of Knowledge is
      illustrated in how Henriques' "Justification Hypothesis" sheds light on the
      nature of institutional disunity.

PMID- 15470736
TI  - Psychology defined.
AB  - A new form of knowledge technology is used to diagnose psychology's
      epistemological woes and provide a solution to the difficulties. The argument
      presented is that psychology has traditionally spanned two separate but
      intimately related problems: (a) the problem of animal behavior and (b) the
      problem of human behavior. Accordingly, the solution offered divides the field
      into two broad, logically consistent domains. The first domain is psychological
      formalism, which is defined as the science of mind, corresponds to animal
      behavior, and consists of the basic psychological sciences. The second domain is
      human psychology, which is defined as the science of human behavior at the
      individual level and is proposed as a hybrid that exists between psychological
      formalism and the social sciences.

PMID- 15470737
TI  - Defining psychology: what can it do for us?
AB  - "Psychology," like many abstract terms, is difficult to define precisely.
      Henriques' (this issue) argument that psychology, though unified and coherent,
      actually spans two realms-psychological formalism ("the science of mind," this
      issue) and human psychology ("the science of human behavior at the individual
      level," this issue)-seems likely to improve the clarity of the concept. The
      strongest contribution of his analysis may be its placing "psychology" in the
      larger conceptual framework of the Tree of Knowledge taxonomy.

PMID- 15470738
TI  - A much needed macro level view: a commentary on Henriques' "psychology defined".
AB  - To develop greater coherence, psychology must develop its macro and integrative
      approaches to the mind. In this illuminating paper, Henriques (this issue)
      outlines the kind of thinking that is needed. He skillfully illuminates the
      levels of emergence of mind from the material world and argues that the recursive
      self-regulative abilities of self-awareness set us apart from other animals. The
      interaction between an evolved mind, adapted to pursue strategic goals, while
      also being phenotypically shaped by both environment and our recently evolved
      cognitive competencies, is a core focus of psychology.

PMID- 15470739
TI  - Some discontents with theoretical unification: a response to Henriques'
      "psychology defined".
AB  - In response to Henriques' article "Psychology Defined" (this issue), I argue that
      theoretical unification should not be pursued for its own sake and that many
      psychologists are unlikely to endorse the specific unifying principles of the
      Tree of Knowledge System. It is suggested that other scholarly endeavors such as
      the open pursuit of truth, sustained dialogue among diverse discourse
      communities, and critical reflection on psychological theories and practice are
      more important than theoretical unification.

PMID- 15470740
TI  - Home-range use and intergroup encounters in western gorillas (Gorilla g. gorilla)
      at Lossi forest, North Congo.
AB  - I present data on home-range use and types of intergroup encounters for one group
      (Apollo) of western gorillas (Gorilla gorilla gorilla) from a new study site in
      the Republic of Congo. The total home-range size of the focal group, which I
      calculated by superimposing a 100 m x 100 m grid over the mapped daily path
      traveled, was 11 km2. The majority (73%) of the group's home range was used
      exclusively, although at the periphery it overlapped with the ranges of three
      other groups. Most encounters (86%) with other groups (n = 14) took place in the
      periphery of the home range, and appeared to involve access to fruit trees. The
      focal group silverback's encounters with solitary silverbacks occurred throughout
      the focal group's home range, did not involve access to fruit, and typically
      resulted in aggressive or avoidance behavior. The focal group silverback's
      response to other group males was more varied: it included tolerance (64%),
      avoidance (14%), and aggression (21%), and was dependent upon the identity of the
      extragroup male. The focal group exhibited an unusual form of tolerant behavior
      toward some other groups by occasionally forming "nesting supergroups" (two
      groups nested together overnight at distances of 30-50 m). The western gorillas
      at Lossi were somewhat fluid in their grouping. Subgrouping and supergrouping
      occurred, although more infrequently than reported previously, and with a new
      twist: subgrouping did not necessarily require a silverback's presence. I stress
      the need for intraspecific comparisons and more complete data sets on western
      gorilla social organization.

PMID- 15470741
TI  - Responses of human keratocytes to micro- and nanostructured substrates.
AB  - We have previously shown that human corneal epithelial cells respond to synthetic
      topographic features with dimensions similar to those found in the native human
      corneal basement membrane. Epithelial cells integrated inputs from substrate
      topography and soluble factors in the culture medium to generate alignment
      responses to substrate topographic anisotropies. Human keratocytes are the main
      cellular components of the stroma, the tissue that underlies the corneal
      epithelium. Here we report that keratocytes aligned more strongly than epithelial
      cells along topographic patterns of grooves and ridges. On patterns with pitches
      of 800 nm and larger approximately 70% of keratocytes were aligned along the
      patterns compared to 35% for epithelial cells. On 70 nm-wide ridges on a 400-nm
      pitch, keratocyte alignment dropped to 45%, whereas epithelial cell alignment
      remained constant. Similarly to epithelial cells, focal adhesions and associated
      stress fibers in keratocytes were aligned mainly along the substrate
      topographies, although oblique orientations were also observed. Furthermore,
      keratocytes cultured on the nanoscale patterns had fewer stress fibers and focal
      adhesions than cells cultured on microscale patterns or on smooth substrates.

PMID- 15470742
TI  - Western gorilla diet: a synthesis from six sites.
AB  - The objective of this paper is to collate information on western gorilla diet
      from six study sites throughout much of their current range, including
      preliminary information from two sites (Afi and Lossi), where studies of diet
      have begun only recently. Food lists were available from each site, derived from
      indirect signs of gorilla feeding (such as feces), with some observational data.
      Important staple, seasonal, and fallback foods have been identified, and a number
      of striking similarities across sites have been revealed based on a much larger
      data set than was previously available. It was confirmed that the western gorilla
      diet is always eclectic, including up to 230 items and 180 species. The greatest
      diversity is found among the fruit species eaten, fruit being included in western
      gorilla diets from all sites and throughout most or all of the year. Eight plant
      families provide important foods at five, or all six, sites, suggesting that it
      may be possible in the future to predict which habitats are the most suitable for
      gorillas. Gorillas exploit both rare and common forest species. Similarities and
      differences among sites can be explained superficially on the basis of geography
      and the past history of the forest. Gorilla density across sites appears to be
      most affected by the density of monocotyledonous bulk food plants, but its
      relationship to the density of important tree food species has yet to be tested.

PMID- 15470743
TI  - Impact of ecological and social factors on ranging in western gorillas.
AB  - We examined the influence of ecological (diet, swamp use, and rainfall) and
      social (intergroup interaction rate) factors on ranging behavior in one group of
      western gorillas (Gorilla gorilla gorilla) during a 16-month study. Relative to
      mountain gorillas, western gorillas live in habitats with reduced herb densities,
      more readily available fruit (from seasonal and rare fruit trees), and, at some
      sites, localized large open clearings (swamps and "bais"). Ranging behavior
      reflects these ecological differences. The daily path length (DPL) of western
      gorillas was longer (mean=2,014 m) than that of mountain gorillas, and was
      largely related to fruit acquisition. Swamp use occurred frequently (27% of days)
      and incurred a 50% increase in DPL, and 77% of the variation in monthly frequency
      of swamp use was explained by ripe fruit availability within the swamp, and not
      by the absence of resources outside the swamp. The annual home-range size was
      15.4 km2. The western gorilla group foraged in larger areas each month, and
      reused them more frequently and consistently through time compared to mountain
      gorillas. In contrast to mountain gorillas, intergroup encounters occurred at
      least four times more frequently, were usually calm rather than aggressive, and
      had no consistent effect on DPL or monthly range size for one group of western
      gorillas. High genetic relatedness among at least some neighboring males [Bradley
      et al., Current Biology, in press] may help to explain these results, and raises
      intriguing questions about western gorilla social relationships.

PMID- 15470744
TI  - Within-group social relationships among females and adult males in wild western
      lowland gorillas (Gorilla gorilla gorilla).
AB  - Within-group female relationships, and relationships between females and adult
      males have not been described for wild western lowland gorillas. New data are
      presented here from Mbeli Bai in the Nouabale-Ndoki National Park, Republic of
      Congo. Nine groups were observed over a continuous 2-year period, and affiliative
      and agonistic interactions, as well as time spent by females and adult males in
      proximity to each other were recorded. Affiliative behavior was extremely rare in
      the bai, and measures of proximity between individuals were inconclusive because
      of the small sample sizes. Rates of agonistic interaction among females were
      highly variable between groups. The majority of agonistic interactions were
      undecided, and the supplant rate was low. Evidence for an agonistic dominance
      hierarchy is weak. The data do not support hypotheses that increased frugivory in
      western lowland gorillas raises levels of within-group contest competition;
      however, the need for intersite comparisons is stressed. In contrast, rates of
      agonistic behavior between females and silverback males were higher and more
      consistent between groups. Agonistic relationships between males and females
      conformed with patterns seen in mountain gorillas, where male protection from
      intraspecific aggression is important. The benefit females gain by forming long
      term cooperative alliances appears to be small, and is likely outweighed by
      reproductive advantages associated with male protection.

PMID- 15470745
TI  - Behavioral ecology of western gorillas: new insights from the field.
AB  - The papers in this issue are from a conference held in May 2002 at the Max Planck
      Institute for Evolutionary Anthropology in Leipzig, Germany. This conference
      brought together researchers from all current western gorilla sites for the first
      time with the aim of synthesizing the most current information available on
      western gorilla behavioral ecology. Our goal was to assess the degree of
      behavioral diversity in gorillas in light of our current understanding of social
      evolution. The articles include 1) synopses of the current information on western
      gorilla foraging strategy, social behavior, life history, and genetic variation;
      2) more-detailed descriptions of home-range use and intergroup encounters across
      sites; and 3) the first description of the social behavior of western gorilla
      females.

PMID- 15470746
TI  - Genetic variation in gorillas.
AB  - This review summarizes what is currently known concerning genetic variation in
      gorillas, on both inter- and intraspecific levels. Compared to the human species,
      gorillas, along with the other great apes, possess greater genetic variation as a
      consequence of a demographic history of rather constant population size. Data and
      hence conclusions from analysis of mitochondrial DNA (mtDNA), the usual means of
      describing intraspecific patterns of genetic diversity, are limited at this time.
      An important task for future studies is to determine the degree of confidence
      with which gorilla mtDNA can be analyzed, in view of the risk that one will
      inadvertently analyze artifactual rather than genuine sequences. The limited
      information available from sequences of nuclear genomic segments does not
      distinguish western from eastern gorillas, and, in comparison with results from
      the two chimpanzee species, suggests a relatively recent common ancestry for all
      gorillas. In the near future, the greatest insights are likely to come from
      studies aimed at genetic characterization of all individual members of social
      groups. Such studies, addressing topics such as behavior of individuals with kin
      and non-kin, and the actual success of male reproductive strategies, will provide
      a link between behavioral and genetic studies of gorillas.

PMID- 15470747
TI  - Effects of group dynamics and diet on the ranging patterns of a western gorilla
      group (Gorilla gorilla gorilla) at Bai Hokou, Central African Republic.
AB  - This study describes how group dynamics and diet have influenced the ranging
      patterns of a western gorilla group at Bai Hokou, Central African Republic. The
      results are compared with those from an earlier study [Cipolletta, International
      Journal of Primatology, 2003], when the same group was larger and undergoing the
      process of habituation to humans. Data were obtained from maps of the gorillas'
      travel routes, direct observations, and analysis of fecal samples. Through the
      years, the group has experienced a decrease in size, from eight to three
      individuals, with periods of membership fluctuation. The male's search for new
      mates resulted in a larger home range than was recorded when the group consisted
      of more individuals. Moreover, despite an average group size of three throughout
      this study, the monthly range and mean daily path length (DPL) were also larger
      when the group was acquiring/losing members in new areas, than when no new
      members joined or left the group. Fruit was consumed year-round, although more
      heavily so during wet months. The influence of fruit consumption on the ranging
      patterns was concealed initially by the effect of habituation [Cipolletta,
      International Journal of Primatology, 2003], and later (at least partially) by
      the male's search for new mates. In the last 14 months of the study, when the
      group numbered only three individuals and was ranging in a restricted area, the
      average DPL, but not the monthly range, increased when the gorillas were
      consuming more fruit.

PMID- 15470748
TI  - The potential calcification of octacalcium phosphate on intraocular lens
      surfaces.
AB  - Recently, calcification was observed on implanted intraocular lens (IOL) surfaces
      when viscoelastic substances were applied during surgery. To elucidate the
      mechanisms of mineral formation, the crystallization of calcium phosphates on IOL
      surfaces was studied in vitro with nanomolar sensitivity using a constant
      composition method. Three different commercial viscoelastic materials (Viscoat,
      OcuCoat, and Amvisc Plus) were investigated and it was found that some IOLs
      treated with Viscoat or Amvisc Plus induced the nucleation and growth of
      octacalcium phosphate crystallites under biological conditions. After treatments,
      the IOL surfaces became more hydrophilic probably because of the high
      viscoelastic phosphate and carboxylate contents. In contrast to Viscoat, the use
      of OcuCoat during surgery resulted in virtually no octacalcium phosphate
      nucleations. Calcification studies of IOL surfaces treated with fatty acids,
      which are present in human aqueous humor, suggest that hydrophobic cyclic
      silicones adsorbed on the IOL surfaces interact strongly with hydrophobic
      hydrocarbon chains of the fatty acids, creating a layer of amphiphiles oriented
      with functional carboxylate groups exposed to the aqueous solution and serving as
      active calcification sites.

PMID- 15470749
TI  - Social structure and life-history patterns in western gorillas (Gorilla gorilla
      gorilla).
AB  - Life-history traits and ecological conditions have an important influence on
      primate social systems. Most of what we know about the life-history patterns and
      social structure of gorillas comes from studies of eastern gorillas (Gorilla
      beringei sp.), which live under dramatically different ecological conditions
      compared to western gorillas (Gorilla gorilla sp.). In this paper we present new
      data on western gorilla social structure and life histories from four study
      sites, and make comparisons with eastern gorilla populations. Data were obtained
      from two study sites with gorilla groups undergoing the habituation process
      (Lossi, Democratic Republic of Congo and Bai Hokou, Central African Republic) and
      two "bai" studies (Maya Nord and Mbeli Bai, Republic of Congo). The size and
      structure of these groups were similar to those seen in eastern gorillas.
      However, differences in the occurrence of various group transitions (group
      formations, changes between one-male and multimale composition, and group
      disintegrations) exist, and western gorillas notably exhibit much higher rates of
      male emigration and correspondingly fewer multimale groups compared to mountain
      gorillas. Certain phenomena have been observed only rarely, including predation
      by leopards. The preliminary data show no significant differences in birth rates
      between western gorillas and mountain gorillas. The ecological variability across
      gorilla habitats likely explains the flexibility in the social system of
      gorillas, but we need more information on the social relationships and ecology of
      western gorillas to elucidate the causes for the similarities and differences
      between western and eastern gorillas on the levels of individuals, social groups,
      and population dynamics.

PMID- 15470750
TI  - Prolongation of levodopa responses by glycineB antagonists in parkinsonian
      primates.
AB  - To examine the antiparkinsonian effects of blocking glycineB receptors, we
      designed a pilot study testing the potent and selective antagonist, PAMQX, in 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates. PAMQX had no
      intrinsic effects but markedly potentiated the antiparkinsonian action of
      levodopa. In a dose-dependent fashion, coadministration of the glycineB
      antagonist with levodopa extended the response duration by nearly 60%. It is
      noteworthy that PAMQX, within a considerable dose range, did not cause ataxia or
      other side effects. These data indicate that blocking N-methyl-D-aspartate
      receptors selectively to manipulate dopaminergic-mediated motor responses may be
      produced effectively by glycineB antagonists.

PMID- 15470751
TI  - A novel endogenous erythropoietin mediated pathway prevents axonal degeneration.
AB  - Clinically relevant peripheral neuropathies (such as diabetic and human
      immunodeficiency virus sensory neuropathies) are characterized by distal axonal
      degeneration, rather than neuronal death. Here, we describe a novel, endogenous
      pathway that prevents axonal degeneration. We show that in response to axonal
      injury, periaxonal Schwann cells release erythropoietin (EPO), which via EPO
      receptor binding on neurons, prevents axonal degeneration. We demonstrate that
      the relevant axonal injury signal that stimulates EPO production from surrounding
      glial cells is nitric oxide. In addition, we show that this endogenous pathway
      can be therapeutically exploited by administering exogenous EPO. In an animal
      model of distal axonopathy, systemic EPO administration prevents axonal
      degeneration, and this is associated with a reduction in limb weakness and
      neuropathic pain behavior. Our in vivo and in vitro data suggest that EPO
      prevents axonal degeneration and therefore may be therapeutically useful in a
      wide variety of human neurological diseases characterized by axonopathy.

PMID- 15470753
TI  - Connexin 32 promoter P2 mutations: a mechanism of peripheral nerve dysfunction.
AB  - We identified a large Charcot-Marie-Tooth disease family with a novel mutation in
      the Connexin 32 (Cx32) P2 promoter region at position -526bp. This mutation was
      in a highly conserved SOX10 binding site. Functional studies were conducted on
      the Cx32 promoter that showed that this mutation reduced the activity of the Cx32
      promoter and the affinity for SOX10 binding. These data suggest that interaction
      between the Cx32 P2 promoter, SOX10, and EGR2 highlight a mechanism of peripheral
      nerve dysfunction.

PMID- 15470752
TI  - cAMP response element-binding protein activation in ligation preconditioning in
      neonatal brain.
AB  - Perinatal hypoxic-ischemic (HI) brain injury is a major cause of permanent
      neurological dysfunction in children. An approach to study the treatment of
      neonatal HI encephalopathy that allows for neuroprotection is to investigate the
      states of tolerance to HI. Twenty-four-hour carotid-artery ligation
      preconditioning established by delaying the onset of hypoxia for 24 hours after
      permanent unilateral carotid ligation rats markedly diminished the cerebral
      injury, however, the signaling mechanisms of this carotid-artery ligation
      preconditioning in neonatal rats remain unknown. Ligation of the carotid artery
      24 hours before hypoxia provided complete neuroprotection and produced improved
      performance on the Morris water maze compared with ligation performed 1 hour
      before hypoxia. Carotid artery ligation 6 hours before hypoxia produced
      intermediate benefit. The 24-hour carotid-artery ligation preconditioning was
      associated with a robust and sustained activation of a transcription factor, the
      cAMP response element-binding protein (CREB), on its phosphorylation site on
      Ser133. Intracerebroventricular infusions of antisense CREB oligodeoxynucleotides
      significantly reduced the 24-hour carotid-artery ligation-induced neuroprotection
      effects by decreasing CREB expressions. Pharmacological activation of the cAMP
      CREB signaling with rolipram 24 hours before hypoxia protected rat pups at
      behavioral and pathological levels by sustained increased CREB phosphorylation.
      This study suggests that 24-hour carotid-artery ligation preconditioning provides
      important mechanisms for potential pharmacological preconditioning against
      neonatal HI brain injury.

PMID- 15470754
TI  - Hoxc8 early enhancer of the Indonesian coelacanth, Latimeria menadoensis.
AB  - Hoxc8 early enhancer controls the initiation and establishment phase of Hoxc8
      expression in the mouse. Comparative studies indicate the presence of Hoxc8 early
      enhancer sequences in different vertebrate clades including mammals, birds and
      fish. Previous studies have shown differences between teleost and mammalian Hoxc8
      early enhancers with respect to sequence and organization of protein binding
      elements. This raises the question of when the Hoxc8 early enhancer arose and how
      it has become modified in different vertebrate lineages. Here, we describe Hoxc8
      early enhancer from the Indonesian coelacanth, Latimeria menadoensis. Coelacanths
      are the only extant lobefinned fish whose genome is tractable to genome analysis.
      The Latimeria Hoxc8 early enhancer sequence more closely resembles that of the
      mouse than that of Fugu or zebrafish. When assayed for enhancer activity by
      reporter gene analysis in transgenic mouse embryos, Latimeria Hoxc8 early
      enhancer directs expression to the posterior neural tube and mesoderm similar to
      that of the mouse enhancer. These observations support a close relationship
      between coelacanths and tetrapods and place the origin of a common Hoxc8 early
      enhancer sequence within the sarcopterygian lineage. The divergence of teleost
      (actinopterygii) Hoxc8 early enhancer may reflect a case of relaxed selection or
      other forms of instability induced by genome duplication events.

PMID- 15470755
TI  - Markers of individual susceptibility and DNA repair rate in workers exposed to
      xenobiotics in a tire plant.
AB  - Workers employed in tire plants are exposed to a variety of xenobiotics, such as
      1,3-butadiene (BD), soots containing polycyclic aromatic hydrocarbons, and other
      organic chemicals (e.g., styrene). In the present study, we investigated markers
      of genotoxicity [chromosomal aberrations (CAs) and single-strand breaks (SSBs)]
      in a cohort of 110 tire plant workers engaged in jobs with different levels of
      xenobiotic exposure in relation to various polymorphisms in genes coding for
      biotransformation enzymes (CYP1A1, CYP2E1, EPHX1, GSTM1, GSTP1, and GSTT1) and in
      genes involved in DNA repair (XPD exon 23, XPG exon 15, XPC exon 15, XRCC1 exon
      10, and XRCC3 exon 7). In addition, the expression of CYP2E1, a gene playing a
      key role in BD metabolism, was determined by real-time PCR in peripheral blood
      lymphocytes, and the capacity of lymphocytes to repair gamma-ray-induced SSBs and
      to convert 8-oxoguanine in HeLa cell DNA into SSBs was assessed using in vitro
      assays. No positive associations were detected between the CA frequency or SSB
      induction and levels of workplace exposure; however, a nonsignificant twofold
      higher irradiation-specific DNA repair rate was found among highly exposed
      workers. In evaluations conducted with the markers of individual susceptibility,
      workers with low-EPHX1-activity genotypes exhibited a significantly higher CA
      frequency as compared to those with medium and high-EPHX1-activity genotypes (P =
      0.050). CA frequencies were significantly lower in individuals homozygous for the
      XPD exon 23 variant allele in comparison to those with the wild-type CC genotype
      (P = 0.003). Interestingly, CAs were higher in individuals with higher CYP2E1
      expression levels, but the association was nonsignificant (P = 0.097). The
      results from this study suggest the importance of evaluating markers of
      individual susceptibility, since they may modulate genotoxic effects induced by
      occupational exposure to xenobiotics.

PMID- 15470756
TI  - An efficient hybrid explicit/implicit solvent method for biomolecular
      simulations.
AB  - We present a new hybrid explicit/implicit solvent method for dynamics simulations
      of macromolecular systems. The method models explicitly the hydration of the
      solute by either a layer or sphere of water molecules, and the generalized Born
      (GB) theory is used to treat the bulk continuum solvent outside the explicit
      simulation volume. To reduce the computational cost, we implemented a multigrid
      method for evaluating the pairwise electrostatic and GB terms. It is shown that
      for typical ion and protein simulations our method achieves similar equilibrium
      and dynamical observables as the conventional particle mesh Ewald (PME) method.
      Simulation timings are reported, which indicate that the hybrid method is much
      faster than PME, primarily due to a significant reduction in the number of
      explicit water molecules required to model hydration effects.

PMID- 15470757
TI  - Enthalpies of formation of monoderivatives of hydrocarbons: Interaction of polar
      groups with an alkyl group.
AB  - Energies of hydrocarbon monoderivatives CH(3)X, C(2)H(5)X, n-C(4)H(9)X, and n
      C(5)H(11)X with 16 different substituents X were calculated at the levels B3LYP/6
      311+G(d,p) and B3LYP/AUG-cc-pVTZ//B3LYP/6-311+G(d,p). The results were used to
      test the validity of the additive rule that has served commonly for estimating
      the enthalpies of formation Delta(f)H(T). The exact additivity corresponds to
      zero reaction energy DeltaE of the isodesmic reaction, in which the substituent X
      is transferred from one alkyl group R to another. Additivity is approximately
      fulfilled for butyl and pentyl derivatives with the differences less than 0.3 kJ
      mol(-1) (except charged groups X). Methyl derivatives deviated from the additive
      rule up to 22 kJ mol(-1) for dipolar groups X and 45 kJ mol(-1) for charged
      group, in agreement with the available experiments and with the anticipation of
      all suggested empirical schemes. In addition, smaller deviations of ethyl
      derivatives (3 or 20 kJ mol(-1), respectively) were observed here for the first
      time. There is no correlation between the deviations of methyl and ethyl
      derivatives; they are also not related to steric effects, and only partly to
      polarization. Deviations of methyl derivatives are proportional to the
      electronegativity of the first atom of the substituent; even when the definition
      of electronegativity is somewhat questionable, one can say in any case that it is
      controlled by the first atom.

PMID- 15470758
TI  - A force-field description of short-range repulsions for high density alkane
      molecular dynamics simulations.
AB  - The use of Buckingham (exp-6) van der Waals potentials in molecular dynamics (MD)
      simulations can quite successfully reproduce experimental thermodynamic data at
      low densities. However, they are less successful in producing a description of
      the repulsive regions of the potential energy surface (PES) that is in accord
      with the results of high-level ab initio computations. We show that Morse
      potentials can be parameterized to give excellent fits to both the attractive and
      repulsive regions of the PES. The best set of alkane van der Waals Morse function
      parameters reported to date for the description of nonbond repulsive interactions
      is presented, as determined by comparison with both ab initio and experimental
      results. C...C, H...H and C...H atom-pair potentials employing parameter sets
      based on the use of the geometric mean in the fitting procedure are found to be
      portable from methane to n-butane. Fitting to a combination of methane dimer
      interaction energies and forces from ab initio calculations yields parameter sets
      whose performance is superior to those determined from the interaction energies
      alone. Used in MD simulations, our newly developed parameter sets predict
      thermodynamic functions that show better agreement with experiment than those
      based on parameter sets in common use.

PMID- 15470759
TI  - Biosafety laboratories proliferate across the USA.

PMID- 15470760
TI  - Trial of antiretroviral for HIV prevention on hold.

PMID- 15470761
TI  - Synthetic antimalaria drug enters clinical trials.

PMID- 15470762
TI  - Emergency initiative to reduce leishmaniasis in Afghanistan.

PMID- 15470763
TI  - Is obesity an infectious disease?

PMID- 15470764
TI  - Fewer colds with increased vitamin E intake.

PMID- 15470765
TI  - Predicting vaccination behaviour.

PMID- 15470766
TI  - Largest de-worming campaign in history happens in Afghanistan.

PMID- 15470767
TI  - India to use AD syringes to stem infection from reused needles.

PMID- 15470768
TI  - Protease inhibitors and risk of developing HIV-related sensory neuropathy.

PMID- 15470772
TI  - [The surveillance and facing new challenge of influenza].

PMID- 15470773
TI  - Cardiac tamponade due to massive pericardial effusion in mixed connective tissue
      disease: reversal with steroid therapy.

PMID- 15470775
TI  - Abstracts of the 27th European Conference on Visual Perception. Budapest,
      Hungary, 22-26 August 2004.

PMID- 15470774
TI  - [Progress in the study of etiology of non-syndromic cleft lip with plate].

PMID- 15470776
TI  - Abstracts of the 40th Annual Scientific Meeting of the Australian and New Zealand
      Society of Nephrology. Adelaide, Australia, 1-3 September 2004.

PMID- 15470777
TI  - Abstracts of the 26th Congress of the European Cystic Fibrosis Society. Belfast,
      Northern Ireland, 4-7 June 2003.

PMID- 15470778
TI  - Abstracts of the 27th European Cystic Fibrosis Conference. Birmingham, United
      Kingdom, 12-17 June 2004.

PMID- 15470779
TI  - Abstracts of REGPEP 2004, the 15th International Symposium on regulatory
      peptides. Toulouse, France, September 19-22, 2004.

PMID- 15470781
TI  - [Abstracts of the XI Colombian Congress of Parasitology and Tropical Medicine.
      Cali, Colombia, 30 October-2 November 2003].

PMID- 15470782
TI  - Ethical issues in the diagnostic genetic testing process.
AB  - The diagnostic genetic testing process has certain unique ethical features and
      deserves special consideration. The purpose of this study was to determine
      through empirical research, using focussed interview, what ethical issues are
      involved in the diagnostic genetic testing process. This article describes views
      and perceptions of adult patients, parents of child patients and various
      personnel groups (n=30). The ethical issues were analysed classified into three
      main categories: a) personnel characteristics, including personality,
      professional skills, morals and values; b) realization of ethical principles in
      the examination process, with subcategories of knowledge, autonomy, data
      protection and equity; and c) consequences of genetic testing, including
      patients' control over their own lives, manifestation of heterogeneity and
      outlook on the world. Problematic ethical issues in all three main categories
      were described in a more many-sided way by parents and personnel than by adult
      patients. In the future, attention should be paid to the content areas
      highlighted by the study, in both clinical practice and further studies.

PMID- 15470783
TI  - Abstracts of the International Society of Neuroimmunology 7th International
      Congress. Venice, Italy, 28 September-2 October 2004.

PMID- 15470784
TI  - Human genetic banking: altruism, benefit and consent.
AB  - This article considers how we should frame the ethical issues raised by current
      proposals for large-scale genebanks with on-going links to medical and lifestyle
      data, such as the Wellcome Trust and Medical Research Council's 'UK Biobank'. As
      recent scandals such as Alder Hey have emphasised, there are complex issues
      concerning the informed consent of donors that need to be carefully considered.
      However, we believe that a preoccupation with informed consent obscures important
      questions about the purposes to which such collections are put, not least that
      they may be only haphazardly used for research (especially that of commercial
      interest)--an end that would not fairly reflect the original altruistic
      motivation of donors, and the trust they must invest. We therefore argue that
      custodians of such databases take on a weighty pro-active duty, to encourage
      public debate about the ends of such collections and to sponsor research that
      reflects publicly agreed priorities and provides public benefits.

PMID- 15470785
TI  - [Abstracts of the VI Meeting of the Society of Nephrology and of the Francophone
      Society of Dialysis. Marseille, France, 28 September-1 October 2004].

PMID- 15470786
TI  - Re: Use of rheolytic thrombectomy in treatment of acute massive pulmonary
      embolism.

PMID- 15470788
TI  - Abstracts of the 44th Annual Meeting of the Society for Psychophysiological
      Research. October 20-24, 2004, Santa Fe, New Mexico, USA.

PMID- 15470787
TI  - "They want to know where they came from": population genetics, identity, and
      family genealogy.
AB  - This paper discusses the changing relationship between population genetics,
      family genealogy and identity. It reports on empirical research with participants
      in a genetic study who anticipated that personal feedback on the analysis of
      their donated samples would elucidate aspects of their own family genealogies.
      The paper also documents how geneticists, building on the practices of offering
      personal feedback to research participants, have developed genetic tests marketed
      directly to people wishing to trace their ancestry. Some of the social and
      ethical issues raised by this development in the use of genetic testing are
      considered.

PMID- 15470789
TI  - Medical ethics education in a problem-based learning curriculum.

PMID- 15470790
TI  - Troubled times for patient autonomy: a delicate balance.

PMID- 15470791
TI  - Are your insurance premiums my problem?

PMID- 15470792
TI  - Einstein's clone.

PMID- 15470793
TI  - Just allocation and medical savings accounts.

PMID- 15470794
TI  - Medical charts and teddy bears.

PMID- 15470795
TI  - Just allocation of reproductive choice: the case of Israel's sick funds.

PMID- 15470796
TI  - Transplant and personal responsibility.

PMID- 15470797
TI  - Naloxone in the treatment of acute dissociative states in female patients with
      borderline personality disorder.
AB  - BACKGROUND: Acute dissociative states are common in patients with borderline
      personality disorder (BPD). However, there are no established pharmacotherapeutic
      treatment options for this severe clinical condition. METHODS: The effect of 0.4
      mg naloxone administered intravenously in acute dissociative states was examined
      as compared to placebo in a double-blind crossover study in nine patients who met
      DSM-IV-criteria for BPD. Dissociative symptoms before and 15 min after a single
      dose of naloxone or saline placebo were assessed using a self-rating instrument
      for dissociation and aversive inner tension (DSS) and the observer-based items of
      the Clinician Administered Dissociative States Scale (CADSS). RESULTS:
      Dissociative symptoms before treatment with naloxone or saline placebo were
      moderate to severe. After injection of either naloxone or placebo, dissociative
      symptoms significantly decreased on the DSS (p < 0.01) and the CADSS (p < 0.05).
      However, there were no significant differences between naloxone and placebo in
      the reduction of symptoms. Patients who showed the most prominent response to
      naloxone fulfilled the highest number of DSM-IV-criteria for BPD. CONCLUSIONS:
      Although it is difficult to draw definite conclusions from this small sample of
      patients, this study does not support the assumption that naloxone in a single
      dose of 0.4 mg is superior to placebo in acute dissociative states in patients
      with BPD. Further studies will investigate whether patients benefit from naloxone
      in a higher dose or whether subgroups of patients with BPD profit from naloxone
      in acute dissociative states.

PMID- 15470798
TI  - The impact of the selective monoamine reuptake inhibitors reboxetine and
      citalopram on visually-evoked event-related potentials in depressed patients.
AB  - OBJECTIVE: The aim of our study was to assess the possible relationship between
      event-related potentials (ERP) and serotonergic or noradrenergic activity in
      depression. Therefore, we were interested in the impact of different monoamine
      reuptake inhibitors on ERP. METHODS: Thirty-six inpatients with major depression
      were treated with either reboxetine (n = 17) or citalopram (n = 19) in a
      prospective randomized study. Before and after four weeks of treatment, visually
      evoked ERP were investigated. Twenty-two patients completed the study.
      Monoaminergic function was determined by oral reboxetine and citalopram challenge
      tests. RESULTS: P3 latency significantly decreased after a four-week treatment
      with either drug. There was no significant difference in the decrease of P3
      latency between both drugs. We detected a significant inverse correlation between
      serotonergic hypofunction before treatment and the P3 latency (r = -0.739, p =
      0.001). CONCLUSIONS: These results show that, in depressed patients, the P3
      latency is decreased by antidepressive treatment. Furthermore, the results
      suggest that P3 latency might depend on the serotonergic rather than the
      noradrenergic system.

PMID- 15470799
TI  - Cardiovascular risk factors in outpatients with bipolar disorder.
AB  - BACKGROUND: The mortality due to cardiovascular diseases in bipolar patients is
      much higher than in the general population. It is unclear whether lithium
      treatment contributes to this cardiovascular morbidity. METHODS: The
      cardiovascular risk factors in outpatients with bipolar disorder on monotherapy
      lithium were explored. Cardiac (family) history, important habits and recent
      stressful events were assessed. Quetelet Index (QI) was calculated and blood
      samples were taken. Blood pressure (BP) was measured in supine position and
      during orthostatic challenge. RESULTS: 40 out of 81 patients on monotherapy
      lithium were studied in detail. In this group, one patient was hypothyroid; six
      patients suffered from hypertension. QI was > 25 in 57.5% of the patients; mean
      cholesterol level was 5.7 mmol/L. Renal functioning, electrolytes and glucose
      concentrations were normal. There were no significant relationships between the
      duration of lithium treatment, the duration of bipolar disorder, recent stressful
      events and hypertension. Out of the group of 81 patients on lithium monotherapy,
      13 patients in total used antihypertensive medication, indicating a high
      prevalence of hypertension in this group as compared to the general population.
      CONCLUSIONS: Cardiovascular risk factors, including hypertension, were increased
      in a large proportion of this population on monotherapy lithium. However, no
      significant relationships were observed between duration of lithium treatment or
      bipolar disorder and presence of hypertension.

PMID- 15470800
TI  - Chronic antidopaminergic medication might affect amygdala structure in patients
      with schizophrenia.
AB  - BACKGROUND: Recently amygdala enlargement has been reported in patients with
      schizophrenia like psychosis of epilepsy. The effect of antipsychotic medication
      on amygdala structure has not been investigated so far. There is theoretical
      evidence to support the assumption that dopaminergic neurotransmission might
      affect neuronal plasticity. METHODS: In order to analyze the influence of chronic
      antidopaminergic medication on amygdala structure we compared amygdala volumes in
      patients with schizophrenia like psychosis of epilepsy (POE) treated with
      neuroleptic medication (n = 11) to patients with POE not treated with such
      medication (n = 15), patients with epilepsy alone (n = 24) and healthy control
      subjects (n = 20). RESULTS: Analyzing our data with a factorial ANOVA approach,
      we found a significant effect of the factor medication in that patients treated
      with antipsychotic medication displayed a "normalization" of the increased
      amygdala volumes observed in the untreated patient group. CONCLUSION: This
      observation supports the assumption that antidopaminergic medication might affect
      the amygdala structure.

PMID- 15470801
TI  - A two-year study on the effects of nicotine and its withdrawal on mood and sleep.
AB  - Acute administration of nicotine has beneficial effects on a variety of
      neurological and psychiatric disorders. The purpose of this study was to
      determine the long-term effects of transdermal nicotine on sleep and major
      depression. Under a single blind protocol study where patients initially received
      nicotine and then switched to placebo. Fourteen non-smoking patients with major
      depression (Hamilton Rating > or = 18) served as subjects. Transdermal nicotine
      (17.5 mg), was administered five days weekly for six months, three days weekly on
      month 7 and one day per week on month 8. From the 9th to the 24th month, once a
      week a patch without nicotine substituted the nicotine patch. Sleep and
      depression was assessed throughout. REM sleep latency changed from 32.6 min. to
      78.2 min. at the end of the study, wakefulness decreased, slow wave sleep
      increased throughout the study and a transient decrease of REM sleep duration
      upon nicotine withdrawal was observed. Hamilton scores went from an initial mean
      score of 29.7 to a final score of 10.8. The results support the possible
      therapeutical effects of long-term transdermal nicotine on sleep and mood, with a
      carryover effect into the withdrawal period, even though, the conclusions should
      be taken with caution due to the design applied.

PMID- 15470802
TI  - Serum levels of substance P and response to antidepressant pharmacotherapy.
AB  - Substance P (SP) is possibly involved in the etiopathology of affective
      disorders. Here we investigated the relationship of SP serum levels and response
      to antidepressant drug therapy. SP serum levels were determined before and during
      a 9-week drug trial in 40 depressed patients treated with paroxetine in
      combination with either lamotrigine (n = 20) or placebo (n = 20). Responders (n =
      18) and non-responders (n = 22) significantly differed in SP serum levels:
      responders started with higher SP levels that decreased during drug therapy,
      whereas non-responders had lower SP levels that increased at the beginning. There
      were no differences between patients with adjunct lamotrigine or placebo. These
      preliminary data indicate that SP serum levels might be related to response to
      antidepressant drug therapy. Further studies have to substantiate this finding.

PMID- 15470803
TI  - Olanzapine augmentation in panic disorder: a case report.
AB  - Chronic and treatment refractory cases of panic disorder are not uncommon. We
      report on a man completely remitted from panic disorder after olanzapine and
      paroxetine combined treatment, and the possible modulating anti-anxiety effect of
      olanzapine is discussed. Olanzapine augmentation in panic and other anxiety
      disorders is deserving of more clinical attention.

PMID- 15470804
TI  - A male case of monosymptomatic hypochondriacal psychosis responding to
      olanzapine: a case report.
AB  - We report the case of a 62-year-old man with monosymptomatic hypochondriacal
      psychosis who failed to respond to paroxetine treatment. Olanzapine addition
      brought about dramatic improvement in the patient's condition and thereafter
      paroxetine withdrawal further eliminated his psychosis. These findings suggest
      that olanzapine itself may be effective for the treatment of monosymptomatic
      hypochondriacal psychosis. Further controlled studies are required, but this is
      the first report describing an olanzapine effect in a male patient with
      monosymptomatic hypochondriacal psychosis.

PMID- 15470805
TI  - Preventing, and managing the impact of, anesthesia awareness.

PMID- 15470806
TI  - Wheeling and healing.

PMID- 15470807
TI  - Protecting profits.

PMID- 15470809
TI  - [Abstracts of the 29th Meeting of the European Society of Pediatric Neurology.
      Bologne, Italy, 25-28 October 2001].

PMID- 15470808
TI  - Enhancing research in academic radiology departments: recommendations of the 2003
      Consensus Conference.
AB  - Opportunities for funded radiologic research are greater than ever, and the
      amount of federal funding coming to academic radiology departments is increasing.
      Even so, many medical school-based radiology departments have little or no
      research funding. Accordingly, a consensus panel was convened to discuss ways to
      enhance research productivity and broaden the base of research strength in as
      many academic radiology departments as possible. The consensus panel included
      radiologists who have leadership roles in some of the best-funded research
      departments, radiologists who direct other funded research programs, and
      radiologists with related expertise. The goals of the consensus panel were to
      identify the attributes associated with successful research programs and to
      develop an action plan for radiology research based on these characteristics.

PMID- 15470810
TI  - Wages, health benefits, and workers' health.
AB  - Employer-based health insurance provides the majority of U.S. workers with access
      to health care and protection against devastating financial losses. Millions of
      workers, however, do not receive health benefits from their employers, and few
      sources of affordable coverage exist outside the employer-based system. This
      study, based on data from the Commonwealth Fund Biennial Health Insurance Survey,
      finds a deep divide in the U.S. labor force and an urgent need for expanding
      access to comprehensive and affordable coverage to working Americans and their
      families. According to the authors, higher-wage workers are more likely than
      their lower-paid counterparts to have health insurance and health-related
      benefits, such as paid sick leave, and to use preventive care services. Low-wage
      workers, meanwhile, are much more likely to forgo needed health care because of
      cost and to report problems paying medical bills.

PMID- 15470811
TI  - Genetic and molecular basis of cardiac arrhythmias. Proceedings of the XIV Paavo
      Nurmi Symposium. Helsinki, Finland, 27-29 August 2003.

PMID- 15470812
TI  - Immunosuppressive Treatments in Multiple Sclerosis. Proceedings of the European
      Charcot Foundation Symposium. Seville, Spain, 28-30 November 2002.

PMID- 15470813
TI  - Voices lost: Indigenous health and human rights in Australia.

PMID- 15470814
TI  - Human rights, drinking rights? Alcohol policy and Indigenous Australians.

PMID- 15470815
TI  - Mental illness in detained asylum seekers.

PMID- 15470816
TI  - Asthma among California's children, adults and the elderly: a geographic look by
      legislative districts.
AB  - Asthma is a chronic lung condition characterized by wheezing, breathlessness,
      chest tightness, and nighttime or early morning coughing; it has been on the rise
      in the United States over the past two decades. In California, about three
      million children and adults who have ever been diagnosed with asthma also
      experienced asthma symptoms at least once in 2002. This policy brief provides
      data for California legislative districts to highlight the variation in asthma
      symptom prevalence for children and adults across the state. Asthma symptom
      prevalence rates at the district level are estimates created by a small-area
      methodology, based on rates from the 2001 California Health Interview Survey
      (CHIS 2001) that are applied to population data from the 2000 Census and 2002
      California Department of Finance. This first-of-its-kind sub-county data are
      relevant for policy makers, advocates, and medical providers to illuminate the
      problem of asthma throughout California and within local communities.

PMID- 15470817
TI  - [Large liver "leech"].

PMID- 15470818
TI  - Electronic health records: How close? How far to go?
AB  - This paper looks at the central role of the electronic health record (EHR) in
      health information technology. It considers the extent to which EHRs are in use
      and initiatives designed to increase their prevalence, as well as barriers to the
      widespread adoption of EHRs and efforts to surmount them. Particular attention is
      given to such obstacles as cost, the professional culture of physicians,
      standardization, and legal questions.

PMID- 15470819
TI  - Cycling exercise and fetal spinal cord transplantation act synergistically on
      atrophied muscle following chronic spinal cord injury in rats.
AB  - The potential of two interventions, alone or in combination, to restore chronic
      spinal cord transection-induced changes in skeletal muscles of adult Sprague
      Dawley rats was studied. Hind limb skeletal muscles were examined in the
      following groups of animals: rats with a complete spinal cord transection (Tx)
      for 8 weeks; Tx with a 4-week delay before initiation of a 4-week motor-assisted
      cycling exercise (Ex) program; Tx with a 4-week delay before transplantation (Tp)
      of fetal spinal cord tissue into the lesion cavity; Tx with a 4-week delay before
      Tp and Ex; and uninjured control animals. Muscle mass, muscle to body mass
      ratios, and mean myofiber cross-sectional areas were significantly reduced 8
      weeks after transection. Whereas transplantation of fetal spinal cord tissue did
      not reverse this atrophy and exercise alone had only a modest effect in restoring
      lost muscle mass, the combination of exercise and transplantation significantly
      increased muscle mass, muscle to body mass ratios, and mean myofiber cross
      sectional areas in both soleus and plantaris muscles. Spinal cord injury (SCI)
      also caused changes in myosin heavy chain (MyHC) expression toward faster
      isoforms in both soleus and plantaris and increased soleus myofiber succinate
      dehydrogenase (SDH) activity. Combined exercise and transplantation led to a
      change in the expression of the fastest MyHC isoform in soleus but had no effect
      in the plantaris. Exercise alone and in combination with transplantation reduced
      SDH activity to control levels in the soleus. These results suggest a synergistic
      action of exercise and transplantation of fetal spinal cord tissue on skeletal
      muscle properties following SCI, even after an extended post-injury period before
      intervention.

PMID- 15470820
TI  - Development of a health-related quality of life measure for peripheral
      neuropathy.
AB  - STATEMENT OF PROBLEM: To develop and evaluate a self-administered health-related
      quality of life (HRQOL) measure for peripheral neuropathy. METHODS: A field test
      measure of 162 items was developed that included the RAND-36 Health Survey as a
      generic core and a neuropathy-targeted supplement whose content was driven by
      results from three focus groups with 22 adults having peripheral neuropathy. It
      was administered at baseline and at 3- and 6-month follow-ups to 80 adult
      clinical trial enrollees with diabetic neuropathy. Item reduction and placement
      into scales, reliability, construct validity, responsiveness, and HRQOL
      comparisons to a general U.S. population were conducted. RESULTS: The final 97
      item instrument includes 16 multi-item scales and 6 single items. Internal
      consistency reliabilities ranged from 0.67 to 0.93 (median = 0.88); intraclass
      correlation coefficients for those reporting no change in health between baseline
      and 3 months ranged from 0.42 to 0.84 (median = 0.77). Factor analysis of scales
      revealed physical and mental health as the two underlying dimensions.
      Correlations between selected HRQOL scales and sociodemographic variables were
      modest; there were more noteworthy associations between HRQOL scales and
      employment, disability days, and neurologic symptom ratings. Associations of
      HRQOL with neurologic examination (strength and reflexes) and with
      electrophysiologic findings were nonsignificant (all p > 0.10). Responsiveness of
      a physical health summary score relative to a criterion of change in subject's
      ratings of neuropathy symptom severity yielded a moderate effect size (= 0.60)
      and a Guyatt statistic exceeding 1.0. CONCLUSIONS: Results provide preliminary
      support for the measure's reliability and validity among adults with diabetic
      peripheral neuropathy. HRQOL was more strongly associated with symptom ratings
      than with examination and electrophysiologic test results.

PMID- 15470821
TI  - Maintenance of oral production in agrammatic aphasia: verb tense morphology
      training.
AB  - We used a single-subject research design to examine long-term maintenance of
      treatment gains in a severely aphasic patient. We used a well-defined therapy
      protocol [i.e., Computerized Visual Communication System (C-VIC) training] to
      target production of tense morphology and an assessment specifically designed to
      measure improvements in the targeted behavior. We first trained Subject #1, a 65
      year-old man with a severe nonfluent aphasia, to produce simple subject-verb
      object sentences, then tense-marked sentences. Remarkable improvement was shown
      and was maintained five months after training was terminated. Sixteen months
      later, he maintained only the ability to produce trained root verb forms. A
      second training was initiated to examine the parameters of training that affect
      maintenance. Maintenance was demonstrated up to a year after termination of
      treatment. We attribute Subject #1's maintained performance to his continued
      involvement in general C-VIC sentence level therapy following tense training.

PMID- 15470822
TI  - Computerized assessment of voluntary control in the shift of the center of
      pressure: a pilot study.
AB  - The aim of the study was to test a new stabilometric platform (BioGP) designed to
      provide visual feedback to patients with balance disorders performing sustained
      voluntary shifts of their center of pressure (COP). Twenty-five outpatients with
      mild to moderate impairments of balance due to multiple sclerosis (MS) and 23
      healthy subjects volunteered for the study. Patients' control of balance in
      static conditions was first rated on the Ataxia Battery and the Motricity Index;
      all subjects were then asked to stand on the platform in front of a large screen
      and try to move a visual target representing the momentary position of their COP
      along two vertical paths and one horizontal paths by appropriate movements of
      their hips and ankles along the lateral and antero-posterior planes. To assess
      the validity of BioGP, clinical scores of static balance were correlated with
      measures of speed and accuracy on the platform tasks. To assess the sensitivity
      of the equipment to poor balance control, patients' measures were compared with
      those of healthy subjects. Pearson's correlation coefficients between the Ataxia
      Battery scores and BioGP data ranged between -0.4 and - 0.82. As a group,
      patients performed statistically worse than controls on most BioGP measures. The
      graphic output of BioGP also contributed to define the dynamic relations between
      momentary COP position and balance control. These preliminary findings suggest a
      possible use of the system as both an evaluation and rehabilitation instrument.

PMID- 15470823
TI  - Initial functional independence measure score and interval post stroke help
      assess outcome, length of hospitalization, and quality of care.
AB  - OBJECTIVE: This study tests the hypothesis that the rehabilitation hospital
      admission functional Independence Measure (FIM) score and interval post stroke
      can be used to define clinically relevant functional recovery goals, estimate
      length of stay, and compare quality of care. BACKGROUND: The effects of time from
      stroke to rehabilitation unit admission on admission and discharge FIM scores,
      length of rehabilitation stay, and change in FIM score/day have not yet been
      reported. METHODS: Analysis was based on prospectively collected data from
      patients admitted to an inpatient stroke rehabilitation unit with FIM scores < or
      = 90 and an initial, unilateral, hemispheric, thrombotic, or embolic stroke who
      were fully independent without the use of an assistive device before their
      stroke. Patients with severe (admission FIM < 54) and moderate (admission FIM 54
      90) stroke deficits were divided into cohorts based on interval from stroke to
      rehabilitation hospital admission: 0-2, 2-4, and 4-6 weeks. RESULTS: Over a 17
      month interval, 87 patients met selection criteria. Significant improvements were
      seen in total FIM scores for all. For those with moderate stroke, all three time
      cohorts reached a FIM score of 102 +/- 2 SEM after 35 +/- 2 days on the
      rehabilitation unit. Patients admitted within 2 weeks of a severe stroke reached
      a plateau FIM score of 72 +/- 6 after 43 +/- 3 days on the rehabilitation unit
      compared with the 2-4 week group (FIM = 57 +/- 5 after 53 +/- 4 days) and the 4-6
      week group (FIM = 54 +/- 10 after 40 +/- 6 days). Complications increased with
      severity of stroke and delay in rehabilitation hospital transfer. CONCLUSIONS:
      Admission FIM score and interval from stroke to rehabilitation hospital admission
      can be used to set FIM outcome goals, predict length of rehabilitation
      hospitalization needed to meet those goals, and compare quality of care across
      institutions with different referral patterns. Our results provide a benchmark
      against which to compare less intense or shorter duration inpatient treatment
      options.

PMID- 15470824
TI  - Long-term tracheostomy ventilation in neuromuscular diseases: patient acceptance
      and quality of life.
AB  - Domiciliary assisted ventilation has been used to prolong life in patients with
      neuromuscular diseases. Although earlier studies suggest that the majority of
      patients are satisfied with their lives, the physician's perception of a
      patient's poor quality of life on assisted ventilation is a major reason for
      discouraging assisted ventilation. In this study, the quality of life was
      assessed in 19 patients with neuromuscular diseases on domiciliary tracheal
      intermittent positive-pressure ventilation for a mean duration of 54 months. An
      attempt was made to compare the quality of life of Duchenne muscular dystrophy
      patients with that of amyotrophic lateral sclerosis patients. More than two
      thirds of patients were satisfied with their lives. Eighty-four percent thought
      they had made the right choice. Patients with amyotrophic lateral sclerosis were
      somewhat more negative or ambiguous toward assisted ventilation and had lower
      life satisfaction scores as compared with Duchenne muscular dystrophy patients.
      Financial stresses were significant. Assisted ventilation should be offered as a
      viable option to patients with neuromuscular diseases. Larger studies may be
      useful in influencing insurance companies to make expenses associated with
      assisted ventilation reimbursable.

PMID- 15470825
TI  - A pilot study of the effect of L-threodops on rehabilitation outcome of stroke
      patients.
AB  - We investigated whether L-threodops (L-DOPS), a norepinephrine precursor,
      improves rehabilitation outcome in patients with initial hemiparetic
      supratentorial ischemic stroke (2 months post stroke). Five patients who agreed
      to be treated with L-DOPS received 45-minute physical therapy (PT) and
      occupational therapy (OT) for 2 months, 3 days a week, with an oral dose of 200
      mg L-DOPS 2 hours before each session, followed by PT and OT without L-DOPS for 2
      months (DOPS group). Eight patients who disagreed received PT and OT for 4 months
      (control). Each group demonstrated comparable age, sex, complications, Mini
      Mental State Examination, and the baseline Functional Independence Measure (FIM,
      DOPS/control = 36/42), Fugl-Meyer (F-M) motor scale (30/27), and ambulation
      endurance (10/9 meters). DOPS group had significantly greater gain than control
      (p < 0.05, Mann-Whitney U test) in FIM score at 4 (51/45) and 6 months (57/49),
      ambulation at 4 (66/16) and 6 months (82/24), and F-M score at 4 months (40/29).
      There were no side effects that required discontinuation of the drug. These
      results suggest that L-DOPS treatment paired with PT and OT may be effective in
      improving functional outcome in stroke.

PMID- 15470826
TI  - Reflex interactions during whole head-and-body tilts are modified by age in
      humans.
AB  - We have demonstrated that lower limb extensor muscle response to tibial nerve
      stimulation is significantly facilitated by whole head-and-body tilt in the
      forward direction. Our aim was to examine whether this reflex interaction is
      influenced by age. Reflexes were elicited in lower limb muscles by electrical
      stimulation (ES) of the right tibial nerve. We compared reflexes during supported
      stance (ESalone) and sudden forward tilting of the whole head-and-body (Tilt+ES)
      between 10 healthy subjects aged 66 +/- 4 years and 13 subjects aged 27 +/- 3
      years. In young subjects the area of response evoked in the ipsilateral vastus
      lateralis (iVL) was significantly increased by 74% during Tilt+ES as compared
      with ESalone (p < 0.05). Moreover, the latency of contralateral VL and soleus
      muscle responses (cVL and/or cSO) was significantly shorter by 61 ms during
      Tilt+ES than ESalone (p < 0.01). In contrast, older subjects showed no
      significant increase in the excitability of iVL muscle response and cVL and/or
      cSO muscle responses during Tilt+ES as compared with ESalone, despite the
      application of similar intensity of ES and head acceleration as in young
      subjects. Our findings showed that the interaction between ES-evoked and tilt
      evoked responses in lower limb extensor muscles is modified with age, which
      suggests modifications of sensorimotor integration involved in balance control.

PMID- 15470827
TI  - Pharmacologic treatment of cognitive deficits and hypersexuality due to "shaken
      baby syndrome".
AB  - OBJECTIVE: To describe the clinical effects of amantadine and propranolol in an
      agitated pediatric patient with cognitive deficits, hyperactivity, and
      hypersexualism secondary to "shaken-baby syndrome." BACKGROUND: Patients with
      shaken-baby syndrome can present with cognitive and behavioral impairments. CASE:
      A 9-year-old girl presented with cognitive impairments secondary to shaken-baby
      syndrome at 3 weeks of age. She was receiving many medications, including
      dextroamphetamine, methylphenidate, and clonidine, that were not effective in
      improving her cognitive status or decreasing her hypersexuality. She was weaned
      from stimulants and clonidine and prescribed amantadine 100 mg bid with
      improvement of attention, concentration, and cognition, although hypersexuality
      remained. She was then started on propranolol 10 mg tid and a gradual increase to
      40 mg tid with amelioration of hypersexuality and hyperactivity and no unwanted
      effects noted. Self-weaning of propranolol was associated with the return of
      hypersexuality. The combination of amantadine and propranolol led to improvement
      of cognition and behavior, especially intellectual functioning and appropriate
      socialization with peers, respectively. CONCLUSION: Cognitive deficits and
      hypersexuality with hyperactive features due to shaken-baby syndrome may respond
      to the drug regimen of amantadine and propranolol.

PMID- 15470828
TI  - "ICDAS"--an international system for caries detection and assessment being
      developed to facilitate caries epidemiology, research and appropriate clinical
      management.

PMID- 15470829
TI  - The decline in dental caries among 12-year-old children in Germany between 1994
      and 2000.
AB  - OBJECTIVE: To determine the prevalence of dental caries in 12-year-old-children
      in 11 of the 16 German Federal States over time following the introduction of
      intensive preventive measures. DESIGN: Cross sectional oral health surveys of
      children aged 12 years were performed in 1994-1995, 1997 and 2000. SUBJECTS:
      After random selection 18,459 (1994-1995), 22,908 (1997) and 24,679 (2000)
      children were examined in schools. METHOD: DMFT and fissure sealants were
      recorded following WHO criteria. Caries was diagnosed at the caries into dentine
      (D3) threshold using visual method without radiography or fiber-optic
      transillumination. RESULTS: The mean DMFT scores for Germany decreased from 2.44
      in 1994-1995 to 1.81 in 1997 and 1.24 in 2000. In 1994-1995 31.1% of 12-year-olds
      had no caries experience (DMFT = 0). The corresponding figures were 42.5% in 1997
      and 55.3% in 2000. The average Significant Caries Index (SiC index) dropped from
      5.25 in 1994-1995 to 4.29 in 1997 and to 3.30 in 2000. The results in different
      federal states showed a wide variation in caries prevalence. In the first
      examination, mean DMFT scores between 2.10 and 3.54 were found, while after the
      third evaluation corresponding values between 1.03 and 1.95 were observed. In
      1997 on average between 0.20 and 2.00 teeth with fissure sealants per child were
      found, the corresponding values in 2000 were between 2.13 and 2.83. CONCLUSION:
      The results of our study show considerable inequalities in oral health in the
      various federal states. Nevertheless, oral health in Germany improved
      considerably between the years 1994 and 2000.

PMID- 15470830
TI  - Use of asthma-drugs and risk of dental caries among 5 to 7 year old Danish
      children: a cohort study.
AB  - OBJECTIVE: To estimate the risk of dental caries in 5-7 year old Danish children
      who received prescriptions for asthma-drugs. DESIGN: Population-based cohort
      study based on data from a prescription registry and dental database. Setting The
      County of North Jutland, Denmark. PARTICIPANTS: 4,920 children born in 1993, and
      followed to the end of 2000. Main outcome measures Dental caries in primary
      canines and molars, and permanent teeth. RESULTS: Between the age 3 and 5 years
      30.4% of the children received one or more prescriptions for asthma-drugs
      compared to 18.8% between 5 and 7 years of age. Children often received two or
      more drugs in combination. Approximately 6% of the children received both inhaled
      cortico-steroids and inhaled beta2-agonists between 3 and 7 years of age. No
      increased risk of caries could be shown in the primary teeth, while the relative
      risk of caries in the permanent teeth was estimated at 1.45 (95% C.I.: 0.99-2.11)
      in children who received prescriptions of both inhaled beta2-agonists and
      corticosteroids between 5 and 7 years. Of the 169 children who received
      prescriptions of both inhaled beta2-agonists and cortico-steroids between the
      ages of 3 and 7 years, the relative risk was estimated at 1.62 (95% C.I.: 1.03
      2.56). CONCLUSIONS: Asthma-drugs may increase the risk of caries in newly erupted
      permanent molars.

PMID- 15470831
TI  - A retrospective study of dental general anaesthesia carried out in children
      living in North Wales 1995-1998.
AB  - OBJECTIVES: To determine the reasons for referral for dental general anaesthesia
      (DGA) in children in North Wales and to ascertain the level of repeat DGA.
      RESEARCH DESIGN: Retrospective study of the clinical records for a random sample
      of 10-year-old children who had a DGA before November 1998. SETTING: DGAs carried
      out at two centres within the Community Dental Service (CDS) in the former county
      of Clwyd, North Wales. METHOD: A random sample of children who had a DGA between
      April 1995 and November 1998 from whose records data was collected regarding the
      reason for referral and outcome. RESULTS: It was found that 26.6% of children had
      received an additional DGA, but the total of 203 additional episodes (including
      third and fourth DGAs) represents a true rate of 31.8%. The General Dental
      Service (GDS) referred more than double the numbers of children than the CDS but
      the referral rate per dentist was reversed with the GDS referring an average of
      5.2 subjects and the CDS 11.9 subjects. Around half of all referrals did not
      include a medical history. CONCLUSIONS: The repeat DGA rate was cause for concern
      as was the quality of referrals.

PMID- 15470832
TI  - The prevalence and severity of fluorosis and other developmental defects of
      enamel in children who received free fluoride toothpaste containing either 440 or
      1450 ppm F from the age of 12 months.
AB  - OBJECTIVE: To assess the impact of a programme regularly supplying free fluoride
      toothpaste to children on the prevalence and severity of fluorosis and other
      developmental defects of enamel. DESIGN: Randomised, controlled, parallel three
      group clinical trial. Two groups received toothpaste containing either 440 or
      1450 ppm F; the third group received no intervention. Children were supplied with
      toothpaste and advice on its use from the age of 12 months until they were 5-6
      years old. The participants were a sub sample of those involved in a study that
      considered the caries benefits of providing free fluoride toothpaste. They were
      eligible if they completed the main study, lived in four of the nine districts
      involved and attended schools with 6 or more eligible participants. SETTING:
      Children from the north west of England consuming drinking water containing less
      than 0.1 ppm F were examined in primary schools. PARTICIPANTS: 3731 children
      completed the main study. Of the 1833 children in the four selected districts,
      927 were from schools with six or more participants. METHOD: Digital images
      encompassing the upper and lower anterior sextants were taken of each child when
      they were 8-9 years old. MAIN OUTCOME MEASURES: Developmental defects of enamel
      and dental fluorosis (TF index) were recorded on upper central incisors from wet
      and dry images. RESULTS: A total of 703 children were included in the data
      analysis. In the 1450 ppm F (n=218), 440 ppm F (n = 226) and control (n = 259)
      groups the prevalence of dental fluorosis (TF > 0) was 17%, 15% and 12% for the
      wet (p > 0.05) and 26%, 24% and 25% for the dry (p > 0.05) photographs
      respectively. The prevalence of TF scores 2 or 3 (highest score) was 5%, 4% and
      2% and for the wet (p > 0.05) and 7%, 4% and 5% for the dry (p > 0.05)
      photographs respectively. All subjects identified with TF score 3 were found in
      the group using the 1450 ppm F toothpaste (3 wet and 4 dry) and there were
      statistically significant differences between the three groups for both wet (p =
      0.03) and dry photographs (p < 0.01). However, the pairwise comparisons between
      the groups failed to attain statistical significance. The highest prevalence and
      severity of demarcated opacities was seen in the control group and for the wet
      photographs the difference between the three groups attained statistical
      significance (p = 0.04). For both the wet and dry photographs the prevalence of
      any enamel defects (including fluorosis) and large demarcated or TF score 3 was
      similar for the three groups (p > 0.05). CONCLUSION: Previously it has been
      reported that only the provision of 1450 ppm F toothpaste provides anticaries
      benefits in a programme of this type. This benefit is accompanied by a slight
      increase in prevalence of TF score 3 but not the overall prevalence of
      developmental defects of enamel. Careful targeting and implementation of a
      programme of this type is required to maximise benefits and minimise risks of
      fluoride exposure.

PMID- 15470833
TI  - Oral health status of institutionalised elderly in Hong Kong.
AB  - OBJECTIVES: To describe the oral health status of institutionalized elderly in
      Hong Kong. METHODS: Older adults in 56 elderly homes were clinically examined in
      the institution by one of two calibrated dentists using standard methods
      recommended by the World Health Organization. Information on their perceived oral
      health status and behaviour was obtained from an interview. RESULTS: A total of
      3153 elderly aged 65 years or above (mean = 79.8) were examined. Around 20% of
      them were edentulous. The mean DMFT score was 23.0 (DT = 2.6; MT = 20.1; FT =
      0.3). The percentage of dentate subjects with healthy gingivae, bleeding on
      probing, calculus, shallow pockets, and deep pockets (according to the highest
      CPI score) were 1, 2, 41, 37 and 20 respectively. Two-thirds of the elderly
      reported having difficulties chewing, and over half had not visited a dentist for
      over 5 years. CONCLUSION: The oral health status of institutionalised elderly in
      Hong Kong is poor and needs to be improved.

PMID- 15470834
TI  - Association between some educational indicators and dental caries experience of
      12-year-old children in developing countries: an ecological approach.
AB  - OBJECTIVE: The aim of this study was to investigate the association between some
      educational indicators and dental caries experience of 12-year-old children in
      developing countries. BASIC RESEARCH DESIGN: The ecological association between
      DMFT levels amongst 12 year olds (DMFT-12 index) with six educational indicators
      (adult literacy rate, mean years of schooling, pupil-teacher ratio for primary
      level, educational expenditure as a percentage of gross national product, primary
      enrollment ratio and percent completing primary level) has been studied using
      developing countries as the unit of analysis. Pearson's correlation analysis and
      stepwise linear multiple regression technique were used to identify the
      significantly associated educational indicators with the DMFT-12 index. RESULTS:
      A negative association between DMFT-12 index and percent completing primary
      education level has been observed (r = -0.509; p < 0.01). Also, stepwise
      regression analysis results have shown that only percent completing primary level
      education is significantly associated with DMFT-12 index scores (partial
      regression coefficient = -0.042; 95% confidence intervals: -0.064, -0.021).
      CONCLUSION: Dental caries experience of 12-year-old children appears to be
      highest in countries with low percent of primary level completion. Percent
      completing primary level education may be considered a good predictor of DMFT-12
      index in developing countries.

PMID- 15470835
TI  - Preventing narcotic adverse events in critical care units.

PMID- 15470836
TI  - Impact of the nurse practitioner role in cardiothoracic surgery.
AB  - Changes in the health care system are necessitating new approaches to acute care
      delivery. The acute care nurse practitioner (NP) role was implemented in the
      cardiothoracic intensive care unit (CVICU) at the University of Alberta Hospital,
      Edmonton, Alberta. An evaluation of the structure, process, and outcomes of this
      new role are presented. A survey was conducted of all health care providers (n =
      90) directly involved with the NP in the CVICU. The unique skills of the NP were
      perceived to have a beneficial impact on patients and families, nurses,
      physicians and other health care providers. Factors affecting the implementation
      of the NP role in CVICU are described.

PMID- 15470837
TI  - Post-anesthesia tracheal extubation.
AB  - Caring for the patient in the post-anesthetic period requires an understanding of
      the intubation and extubation process. The nurse must be knowledgeable of the
      numerous tracheal extubation-related complications that can occur. Tracheal
      extubation is a vulnerable period for the patient; there is risk of aspiration,
      laryngospasm, a cardiovascular response, or hypoventilation occurring. In this
      article, the author reviews the more common post-extubation difficulties, risk
      factors, and treatment modalities. After reviewing extubation criteria and the
      safe extubation process, the nurse can apply this knowledge to patient care.
      Although nurses are excellent initiators of tracheal extubation, the procedure is
      ideally performed by an anesthetist or internist who can treat complications that
      arise, or re-intubate the patient, if required.

PMID- 15470838
TI  - About critical thinking.
AB  - Although a universally accepted definition of critical thinking has yet to be
      determined, there is much discussion in the literature about its meaning and, in
      particular, how it can be expressed in professional nursing practice. The
      simultaneous use of related terms such as reflective thinking, problem solving
      and clinical decision-making contributes to the lack of clarity around exactly
      what critical thinking is and, subsequently, how it can be taught and evaluated
      in the clinical setting. The purpose of this article is to provide an overview of
      the various components of critical thinking and to discuss barriers, facilitators
      and strategies that can enhance nurses' attainment of this core competency. Few
      would argue that registered nurses today must be able to think critically in
      order to effectively communicate a nursing perspective that reflects a meaningful
      clinical grasp and preparedness to act.

PMID- 15470839
TI  - The right to a 'good death'.

PMID- 15470840
TI  - Are you still listening?

PMID- 15470841
TI  - Rock of ages.

PMID- 15470842
TI  - Care home placement: can admission direct from acute hospital be justified?

PMID- 15470843
TI  - Introducing a physical activity group on an intermediate care ward.

PMID- 15470844
TI  - Power in care homes.

PMID- 15470845
TI  - The evidence base for gerontological nursing practice. Part 1: What do we mean by
      'evidence'?
AB  - In recent years, 'evidence-based practice' has featured increasingly in the
      lexicon of healthcare practitioners. But what does it mean and how is 'evidence'
      gathered, graded and described? In the first of two articles, Jan Draper explores
      the issues.

PMID- 15470846
TI  - Beta-blockers.

PMID- 15470847
TI  - Ask the experts.

PMID- 15470848
TI  - Petroleum jelly myth.

PMID- 15470850
TI  - Trailblazing in the fens.

PMID- 15470849
TI  - Testing times.

PMID- 15470851
TI  - The pursuit of healthcare.

PMID- 15470852
TI  - A personal reflection on the nursing shortage.

PMID- 15470854
TI  - Postoperative pulmonary dysfunction in adults after cardiac surgery with
      cardiopulmonary bypass: clinical significance and implications for practice.
AB  - Postoperative pulmonary complications are the most frequent and significant
      contributor to morbidity, mortality, and costs associated with hospitalization.
      Interestingly, despite the prevalence of these complications in cardiac surgical
      patients, recognition, diagnosis, and management of this problem vary widely. In
      addition, little information is available on the continuum between routine
      postoperative pulmonary dysfunction and postoperative pulmonary complications.
      The course of events from pulmonary dysfunction associated with surgery to
      discharge from the hospital in cardiac patients is largely unexplored. In the
      absence of evidence-based practice guidelines for the care of cardiac surgical
      patients with postoperative pulmonary dysfunction, an understanding of the
      pathophysiological basis of the development of postoperative pulmonary
      complications is fundamental to enable clinicians to assess the value of current
      management interventions. Previous research on postoperative pulmonary
      dysfunction in adults undergoing cardiac surgery is reviewed, with an emphasis on
      the pathogenesis of this problem, implications for clinical nursing practice, and
      possibilities for future research.

PMID- 15470853
TI  - Effect of kinetic therapy on pulmonary complications.
AB  - BACKGROUND: Optimal turning of critically ill patients is not well established.
      Kinetic therapy (systematic mechanical rotation of patients with 40 degree turns)
      may improve pulmonary function more than the improvement in function achieved via
      the standard of care (turning patients every 2 hours). OBJECTIVE: To determine
      (1) if patients receiving mechanical ventilation who tolerate kinetic therapy
      have better pulmonary function than do patients treated with standard turning and
      (2) the cost-effectiveness of kinetic therapy. METHODS: A prospective,
      randomized, multicenter study including 234 medical, surgical, and trauma
      patients (137 control patients, 97 patients receiving kinetic therapy). RESULTS:
      Kinetic therapy significantly decreased the occurrence of ventilator-associated
      pneumonia and lobar atelectasis. The risk of pneumonia developing was lower (P =
      .002) in patients receiving kinetic therapy than in the control patients. The
      risk of lobar atelectasis developing was decreased (P = .02) for the patients
      receiving kinetic therapy. Lengths of stay in the intensive care unit and in the
      hospital did not differ between the groups. Charges for intensive care were less
      in the kinetic therapy group (81,700 dollars) than in the control group (84,958
      dollars), but not significantly less. Twenty-one patients did not tolerate
      kinetic therapy and were not included in the analysis. CONCLUSION: Kinetic
      therapy helps prevent ventilator-associated pneumonia and lobar atelectasis in
      critically ill patients. Costs to rent the bed may be offset by the potential
      cost reduction associated with kinetic therapy.

PMID- 15470855
TI  - Role of diastole in left ventricular function, I: Biochemical and biomechanical
      events.
AB  - Left ventricular diastolic function plays an important role in cardiac
      physiology. Lusitropy, the ability of the cardiac myocytes to relax, is affected
      by both biochemical events within the myocyte and biomechanical events in the
      left ventricle. Beta-adrenergic stimulation alters diastole by enhancing the
      phosphorylation of phospholamban, a substrate within the myocyte that increases
      the uptake of calcium ions into the sarcoplasmic reticulum, increasing the rate
      of relaxation. Troponin I, a regulatory protein involved in the coupling of
      excitation to contraction, is vital to maintaining the diastolic state; depletion
      of troponin I can produce diastolic dysfunction. Other biochemical events, such
      as defects in the voltage-sensitive release mechanism or in inositol triphosphate
      calcium release channels, have also been implicated in altering diastolic tone.
      Extracellular collagen determines myocardial stiffness; impaired glucose
      tolerance can induce an increase in collagen cross-linking and lead to higher end
      diastolic pressures. The passive properties of the left ventricle are most
      accurately measured during the diastasis and atrial contraction phases of
      diastole. These phases of the cardiac cycle are the least affected by volume
      status, afterload, inherent viscoelasticity, and the inotropic state of the
      myocardium. Diastolic abnormalities can be conceptualized by using pressure
      volume loops that illustrate myocardial work and both diastolic and systolic
      pressure-volume relationships. The pressure-volume model is an educational tool
      that can be used to demonstrate isolated changes in preload, afterload, inotropy,
      and lusitropy and their interaction.

PMID- 15470856
TI  - Cardiovascular single-unit stay: a case study in change.
AB  - A cardiovascular single-unit-stay program began at North Memorial Medical Center,
      Robbinsdale, Minn, in January 2000. Before then, cardiac surgery patients had
      been admitted to the intensive care unit directly from the operating room and
      then transferred to the postcoronary care unit on postoperative day 1 or 2. The
      traditional care delivery model created multiple transfers and delays in care,
      which often led to dissatisfaction among patients, increased costs, and greater
      potential for errors. The cardiovascular single-unit-stay program allows patients
      to stay in the same room with a consistent care team throughout the patients'
      postoperative course. Decreased lengths of stay, decreased morbidity and
      mortality, increased satisfaction among patients and their families, and improved
      collaboration between members of the multidisciplinary team are just a few of the
      positive trends since the program's inception.

PMID- 15470857
TI  - Secondary prevention of hyperlipidemia after coronary artery bypass graft: from
      acute care to primary care.
AB  - BACKGROUND: Clinical trials have established that secondary prevention of
      hyperlipidemia in patients after coronary artery bypass graft (CABG) surgery
      prevents progression of atherosclerosis. A multidisciplinary team promotes
      secondary prevention by prescribing antihyperlipidemic agents, screening for risk
      factors, and providing education on disease, diet, and medications. Information
      is minimal on the number of patients who continue with antihyperlipidemic therapy
      or follow-up with a primary care provider for cholesterol management after
      antihyperlipidemic therapy is initiated in an acute surgical setting. OBJECTIVES:
      To determine (1) the frequency of use of antihyperlipidemic agents before CABG
      surgery, at hospital discharge, and approximately 9 months after discharge and
      (2) the occurrence of cholesterol monitoring by a primary care provider at least
      once between discharge and telephone follow-up. METHODS: Observational study of
      135 patients undergoing CABG surgery at a regional medical center during a 4
      month period. Patients were contacted by telephone between 5 and 12 months after
      discharge and asked about continued use of antihyperlipidemic agents and
      cholesterol monitoring since discharge. RESULTS: Before surgery, 56% of the
      patients were taking an antihyperlipidemic agent. At discharge, 95% were taking
      an antihyperlipidemic agent. At the time of study follow-up, 91% were still
      taking an antihyperlipidemic agent, and 84% had follow-up cholesterol monitoring
      by their primary care provider. CONCLUSION: Initiation of an antihyperlipidemic
      agent and provision of education during hospitalization for CABG surgery results
      in a high percentage of patients continuing antihyperlipidemic therapy and having
      cholesterol levels monitored by their primary care provider after discharge.

PMID- 15470858
TI  - Lived experience of critically ill patients' family members during
      cardiopulmonary resuscitation.
AB  - BACKGROUND: During resuscitative efforts, patients' family members are often
      barred from the patients' rooms and may never have the opportunity to see their
      loved ones alive again. Recently, the need to ask family members to leave the
      room is being questioned. Little is known about families' perceptions of
      cardiopulmonary resuscitation. OBJECTIVE: To describe the experiences, thoughts,
      and perceptions of family members of critically ill patients during
      cardiopulmonary resuscitation in the intensive care unit. METHOD: Six family
      members whose loved ones underwent cardiopulmonary resuscitation and survived
      consented to an audiotaped interview. During the interview, family members were
      asked to describe their experiences during the resuscitation. Interviews were
      transcribed and were analyzed for relevant themes by using Van Manen thematic
      analysis. RESULTS: One major theme emerged. Should we go or should we stay?
      Additionally, 2 subthemes emerged: What is going on? and You do your job. A
      model, the family's experience with cardiopulmonary resuscitation, was developed
      to reflect the research findings. CONCLUSIONS: During the period of
      resuscitation, healthcare professionals neglect to recognize that patients'
      family members are experiencing crisis along with the patients and that coping
      mechanisms are impaired. Moreover, the family members' informational and
      proximity needs are often ignored during this time of crisis. Addressing these
      needs through appropriate nursing interventions will become increasingly
      important as patients' family members begin to remain with their loved ones
      during cardiopulmonary resuscitation.

PMID- 15470859
TI  - Critical illness polyneuropathy in adults after cardiac surgery: a case study.

PMID- 15470860
TI  - Designing formal classification systems to better articulate knowledge, skills,
      and meanings in nursing practice.

PMID- 15470861
TI  - A silent killer--often preventable.
AB  - Deep vein thrombosis and its potentially fatal complication, PE, accounts for
      more than 250,000 hospitalizations annually in the United States. Pulmonary
      embolism is the most serious complication and has a 3-month mortality of 17%. Two
      million people each year are affected by VTE, and the prevalence is rising
      because of the aging population. Deep vein thrombosis and its potential
      complication, PE, is preventable. However, there still is widespread failure to
      screen, diagnose, and initiate prophylactic therapy in patients at risk. This
      failure can be corrected by development of a heightened awareness of risk factors
      among emergency department physicians and nurses and by similar personnel caring
      for bedridden hospitalized patients. A recent landmark study Prophylaxis in
      Medical Patients With Enoxaparin Study (MEDENOX) revealed the risk factors of VTE
      in order of frequency: (1) previous VTE, (2) acute infectious disease, (3)
      cancer, (4) age greater than 75 years, and (5) chronic respiratory disease. This
      study confirmed the effectiveness of a LMWH, enoxaparin, in the prevention of
      VTE.

PMID- 15470862
TI  - An evolving myocardial infarction.

PMID- 15470863
TI  - [Variation in the composition of Rhodococcus rodochrous GNP-OHP-38r cell membrane
      fatty acids in response to temperature and salinity].
AB  - The members of the genus Rhodococcus are frequent and abundant inhabitants of
      polluted areas with hydrocarbons and they resist the salinity present in the
      central Patagonia. This genus has good capacity to eliminate pollution produced
      by hydrocarbons that constitutes the biggest pollutant agent in the region. The
      present work studies the answer in the composition of its fatty acids under the
      combined action of the temperature and saline concentration of an isolated stump
      of a landfarming system. The strategy of Rhodococcus rodochrous strain GNP-OHP
      38r in front of the thermal-osmotic stress is the increase of the percentage of
      the total saturated fatty acids (n:0); fatty acids branched in the terminal
      carbon with hidroxyl group in position 2 (n:0 iso 2 OH) and saturated with group
      methyl in carbon 10 (n:0 10 metil) when the temperature is increased. These acids
      increase while the percentage of n:1 cis decrease.

PMID- 15470864
TI  - [Immunodiagnosis of endemic mycoses and bronchopulmonary aspergillosis: a
      multicenter study in Argentina].
AB  - In order to contribute to the knowledge of the relative frequency of chronic
      fungal diseases and assess the performance of diagnostic laboratories in
      Argentina, a multicenter study was performed with the participation of 25 medical
      centers located in 12 different provinces and Buenos Aires City. Between 04-01
      2000 and 03-30-2001, 965 serum specimens from patients clinically suspected of
      having histoplasmosis (HP), paracoccidioidomycosis (PCM), coccidioidomycosis (CM)
      or aspergilosis were analyzed. Agar immunodiffusion tests (IDD) were done
      locally. All positive and 35% of negative sera were retested in the reference
      center. Results of laboratories of origin showed 98.8% concordance with those of
      reference center. Antibodies against any of the etiological agents were detected
      in 120 specimens from 98 patients. Endemic mycoses (HP, PCM and CM) were
      diagnosed in 70 patients (71.4%) and aspergilosis in 28 (28.6%). The frequencies
      of the different mycoses in decreasing order were PCM 47 patients (47.9%),
      aspergilosis 28 patients (28.6%), HP 13 patients (13.3%) and CM 10 patients
      (10.2%). The study was carried out on a voluntary basis and some areas of the
      country were not represented. However, the frequencies were in range with the
      expected rates in the population under study.

PMID- 15470865
TI  - [Necrotizing lymphadenitis caused by Nocardia asteroides in a healthy girl].
AB  - A case of a healthy girl with a trauma in her right leg is described. Twelve
      hours later she developed fever and pain in the inguinal region. Two days later,
      she was admitted to the Hospital, and there, an aspiration of pus from the lymph
      node was performed, and this sample was sent for culture. The Gram smear showed
      gram-positive filamentous bacilli and when Kinyoun was used they were observed as
      weakly acid fast rods. After four days of incubation under aerobic conditions,
      white and hemolitic colonies were seen on human blood agar plates. Biochemical
      tests as urea hydrolysis and gelatin liquefaction were performed. To complete the
      identification it was sent to a reference laboratory, INEI-ANLIS Dr. Carlos G.
      Malbran, where the isolate was confirmed as Nocardia asteroides sensu stricto.
      The patient was treated with intravenous cephalotin with good evolution. Therapy
      was followed with oral trimethoprim-sulfamethoxazole. This case is the first
      report of a Nocardia infection in the Hospital de Ninos de Santa Fe. The fact
      that N. asteroides was isolated from an immunologically competent girl should be
      highlighted. This species is uncommon in children and it is rare in our region.
      In addition, N. asteroides infections are usually seen in pulmonary disease and
      rarely producing cutaneous infections.

PMID- 15470866
TI  - Unusual phenotypic characteristic of Neisseria gonorrhoeae from male patients who
      have sex with men.
AB  - We describe four isolates of Ng from men who have sex with men (MSM) patients
      that were able to grow in the abscense of CO2, as previously was described for N.
      gonorrhoeae ssp. kochii. These isolates were able to grow aerobically (without
      any added CO2) at 37 degrees C giving small colonies after 48 hs; two of them
      isolated from pharynx and urethra of one patient, were also able to grow without
      the blood supplement in the same conditions. In these unusual isolates the major
      outer-membrane proteins are of the same molecular weight than Ng. These isolates
      could be taken for other members of the genus if not confirmed by means of these
      (or other) methods.

PMID- 15470867
TI  - [Bacteremia by Brucella canis. Isolation with the Bact-Alert system].
AB  - Brucella canis and other species of the genus Brucella can cause human disease.
      However, this species infrequently cause human disease, including in countries
      where dogs population is highly infected. A 15 years old male was admitted to the
      hospital with 15 days history of fever without visible focus. Physical
      examination revealed pain at liver palpation and axillar, cervical and inguinal
      lymphoadenomegalies. Abdominal ultrasonography showed spleenomegally, the chest
      Rx and the trans thoracic echocardiogram were normal. Five blood samples were
      obtained and cultured in 2 standards bottles (time of positivization 72 - 64.8
      hours), and 3 pediatric FAN bottles (time of positivization 74.5; 72 and 67.2
      hours) (Bact-Alert system, Biomerieux, Marcy, l'Etolie, France). The
      microorganism was presuntive identified as B. canis, and then was confirmed in
      the National Reference Center Instituto ANLIS "Carlos G. Malbran". After 14 days
      of initiating ceftriaxone treatment the patient was afebrile. When the
      confirmation of Brucella was made, he was discharged and ambulatory was
      prescribed with doxycycline and rifampin for 21 days. Bones were not compromised
      and the outcome was good with complete resolution of his illness.

PMID- 15470868
TI  - [Evaluation of 61 episodes of infective endocarditis in intravenous drug abusers
      and human immunodeficiency type-1 virus infection].
AB  - We conducted a retrospective evaluation to determine the clinical and
      microbiological characteristics of 61 episodes of infective endocarditis (IE) in
      intravenous drug abusers (IDA), HIV seropositive patients. Forty-nine males and 6
      females between 15 and 42 years of age were included in the study. All the
      included patients presented 61 episodes of IE. Fever and cardiac murmur were
      present in all episodes; 43 (70.4%) had hepatomegaly; 29 (47.5%) had
      splenomegaly. Thirty-eight (62.3%) presented cough (9 with hemoptysis); 25 (41%)
      had dyspnea, and 5 (8.2%) had jugular ingurgitation. Fundoscopy showed
      alterations in 3 patients (4.9%). Bacteriological confirmation was obtained in 41
      episodes (67.2%); blood cultures revealed Staphylococcus aureus in 30 cases
      (73.1%), Streptococcus viridans in 8 (19.5%) patients, Staphylococcus epidermidis
      in 1 (2.4%), Staphylococcus hominis in 1 (2.4%) and Streptococcus pneumoniae in
      one case (2.4%). The tricuspid valve was involved in 51 episodes (83.6%), the
      aorta in 6 (9.8%), the mitral valve in 3 (4.9%) and the pulmonary valve in one
      (1.6%). There was evidence of right bivalvular involvement in 2 patients (3.2%)
      and tricuspid and mitral involvement in another (1.6%). Pericardial effusion was
      detected in 19 episodes (31.1%). Six patients (10.9%) died during the acute
      episode of IE.

PMID- 15470869
TI  - [Antiviral sensitivity of herpes simplex virus in immunocompromised patients].
AB  - The Herpes simplex Virus (HSV) resistance to acyclovir (ACV) occurs in a 5% of
      the inmunocompromised patients, approximately. The treatment with analogs of
      nucleosides, causes the appearance of resistent HSV-ACV stocks (ACVr) which can
      be produced by alteration in genes coding for the TK or the DNA-polymerase. A
      previous large-scale clinical study on ACVr HSV strains isolated from patients
      infected with human immunodeficiency virus indicated that 96% of ACVr HSV mutants
      were low producers of, or deficient in, TK activity (TK-), with 4% being TK
      mutants with an altered substrate specificity. No DNA Pol mutants were isolated.
      The pirophosphate analogs generate resistance in the gene of DNA-polymerase by
      mutation. In this paper we show the methodology used for the determination of
      sensibilite profiles to ACV and Phoscarnet (PFA) in a population of
      inmunocompromised patients. We analized 46 HSV strain from vesicular injuries of
      transplanted patients. All samples, were inoculated in human fibroblasts and the
      HSV isolates were identified by inmunofluorescence whith monoclonal antibodies.
      These strains were amplified and the profile of susceptibility determinated in
      Vero cells, using 100 tissue culture inhibition dosis 50 (TCID50) of each Viral
      stock and the specific antiviral drugs in different concentrations. The
      cytopathic effect (CPE) was evaluated after 72hs. post infection. The 50%
      inhibitory concentration (CI50) was calculated from the percentage of inhibition
      of the ECP based on the concentration of the drug. From 46 isolations, 26 were
      HSV-1 and 20 were HSV-2. Two of them, one HSV-1 and one HSV-2, were resistant to
      ACV and none of the isolates were resistant to PFA.

PMID- 15470870
TI  - [The action of different coagulants to remove Cryptosporidium during the process
      of water treatment].
AB  - Cryptosporidium is one of the microorganisms of main concern from the point of
      view of Public Health, being a priority problem for water treatment plants and
      water regulatory institutions. Due to its small size and resistance to
      chlorination, Cryptosporidium removal during the process of drinking water
      treatment is a hard task. The effectiveness of different coagulants commonly used
      in the process of removal of oocysts was analyzed. The technique used was the Jar
      Test. It was found that: 1) coagulants with the addition of polimeric coadjuvants
      produce over 2 logs of oocyst removal; 2) a low value in turbidity does not
      necessarily mean optimal parasite removal, and 3) the addition of
      polyelectrolites to ferric chloride diminishes variability, both in final
      turbidity and Cryptosporidium removal.

PMID- 15470871
TI  - Buonocore Memorial Lecture. Review of the clinical survival of direct and
      indirect restorations in posterior teeth of the permanent dentition.
AB  - This review provides a survey on the longevity of restorations in stress-bearing
      posterior cavities and assesses possible reasons for clinical failure. The dental
      literature, predominantly since 1990, was reviewed for longitudinal, controlled
      clinical studies and retrospective cross-sectional studies of posterior
      restorations. Only studies investigating the clinical performance of restorations
      in permanent teeth were included. Longevity and annual failure rates of amalgam,
      direct composite restorations, compomers, glass ionomers and derivative products,
      composite and ceramic inlays and cast gold restorations were determined for Class
      I and II cavities. Mean (SD) annual failure rates in posterior stress-bearing
      cavities are: 3.0% (1.9) for amalgam restorations, 2.2% (2.0) for direct
      composites, 3.6% (4.2) for direct composites with inserts, 1.1% (1.2) for
      compomer restorations, 7.2% (5.6) for regular glass ionomer restorations, 7.1%
      (2.8) for tunnel glass ionomers, 6.0% (4.6) for ART glass ionomers, 2.9% (2.6)
      for composite inlays, 1.9% (1.8) for ceramic restorations, 1.7% (1.6) for CAD/CAM
      ceramic restorations and 1.4% (1.4) for cast gold inlays and onlays. Publications
      from 1990 forward showed better results. Indirect restorations exhibited a
      significantly lower mean annual failure rate than direct techniques (p=0.0031).
      Longevity of dental restorations is dependent upon many different factors,
      including material, patient- and dentist-related. Principal reasons for failure
      were secondary caries, fracture, marginal deficiencies, wear and postoperative
      sensitivity. We need to learn to distinguish between reasons that cause early
      failures and those that are responsible for restoration loss after several years
      of service.

PMID- 15470872
TI  - Effect of luting cement on dental biofilm composition and secondary caries around
      metallic restorations in situ.
AB  - Since the importance of luting cement on secondary caries in enamel and dentin is
      unknown, an in situ crossover study was conducted in three phases over 21 days
      using a fluoride-containing toothpaste. One hundred and twenty-six metallic
      restorations were cemented into the dentinoenamel junction of slabs of human
      teeth with zinc phosphate (ZP), resin-modified glass ionomer (GI) or resinous
      cement (RC). The slabs were inserted onto flanges of the removable partial
      acrylic dentures of 14 volunteers and covered with gauze to enhance dental plaque
      accumulation. The volunteers used fluoride toothpaste (1.100 microg F/g, w/w).
      After 21 days, the biofilm that formed on the slabs was collected for biochemical
      and microbiological analyses, and the demineralization in enamel-dentin around
      the restorations was evaluated. The fluoride concentration of biofilm in the GI
      group was higher (p<0.05) than the ZP and RC groups. Also, the concentration of
      Zinc in biofilm formed on the slabs cemented with ZP was higher (p<0.05) than the
      other groups. However, the effect of the luting material on enamel or dentin
      demineralization was not statistically significant (p>0.05). The data suggest
      that when fluoride toothpaste is used, the anticariogenic property of the luting
      cement may not be relevant to the reduction of secondary caries.

PMID- 15470873
TI  - Clinical evaluation of a polyacid-modified resin composite under different
      conditioning methods in primary teeth.
AB  - This study evaluated the clinical performance of a polyacid-modified resin
      composite, Dyract AP (De Trey/Dentsply), under different conditioning methods in
      primary teeth. Eighty-one box-shaped cavity preparations (three restorations per
      patient) on the mesial or distal surfaces of primary first or second molars were
      prepared in 27 patients. The cavity preparations were either non pre-treated or
      pre-treated with 36% phosphoric acid or NRC (De Trey/Dentsply). The teeth were
      restored with Prime & Bond NT (De Trey/Dentsply) and Dyract AP. The restorations
      were evaluated at baseline and 6, 12 and 18-month recalls according to the
      modified Ryge criteria by two calibrated operators. The data obtained from the
      clinical assessment of all restorations were subjected to statistical analysis by
      chi-square-tests at a 0.05 level of significance. The ratings of each criteria
      were compared among each evaluation period between treatment groups. Statistical
      analysis revealed no significant difference among each evaluation period between
      groups in regard to color match, marginal discoloration, marginal adaptation,
      secondary caries, surface texture, anatomic form and retention.

PMID- 15470874
TI  - Fluoride releasing materials: their anti-cariogenic properties tested in in vitro
      caries models.
AB  - The anti-cariogenic properties of three fluoride-releasing materials on root
      surfaces were evaluated using two different caries models. Standardized cavities
      were prepared in dentin specimens and restored with either glass-ionomer, resin
      modified glass-ionomer, polyacid-modified resin composite or resin composite
      material. Two groups of 56 specimens were demineralized using a microbial caries
      model for three days, while another 56 specimens were demineralized using a
      chemical demineralization model for three days. Lesions around the restorations
      were measured with a confocal laser scanning microscope. Glass ionomers
      demonstrated significant anti-cariogenic properties when exposed to the chemical
      model. However, no significant anti-cariogenic properties were observed with the
      microbial caries model. In conclusion, the fluoride releasing materials showed
      different anti-cariogenic properties in root surfaces under the different caries
      models, suggesting that caution should be exercised when trying to extrapolate
      the results of in vitro studies to the clinical situation.

PMID- 15470875
TI  - Influence of interchanging adhesive resins and self-etching primers on the
      mechanical properties of adhesive resins.
AB  - This study determined the influence of interchanging adhesive resins and self
      etching primers on the mechanical properties of adhesive resins. Four
      commercially available two-step self-etching primer systems were used. To measure
      microtensile strength, 0.5-mm thick dumbbell-shaped slabs of each combination of
      adhesive resin and self-etching primer were prepared. After 24 hours storage in
      37 degrees C distilled water, these specimens were subjected to microtensile
      testing at a crosshead speed of 1.0 mm/minute. Fourier transformation infrared
      spectroscopy was used to determine the degree of conversion. The percentage of
      residual double bonds, including pendant and monomeric double bonds, was
      calculated by comparing the obtained ratio against uncured adhesive resin. The
      degree of conversion of the adhesive resins was obtained by subtracting the %C=C
      from 100%. Two-way ANOVAs, followed by Tukey tests, were done. The microtensile
      strengths and degree of conversion varied with different combinations of self
      etching primer and adhesive resin. Numerically, the highest microtensile
      strengths were obtained when the primer/adhesive resin combinations from the same
      manufacturer were used. When the different combinations of self-etching primers
      and adhesive resins were mixed, the microtensile strength and degree of
      conversion of the adhesive resins tended to decrease for some combinations.
      Within the limitations of this study, which was far removed from clinical
      situations, the role of the self-etching primers on the mechanical properties of
      adhesive resins should be considered to create an authentic resin-dentin
      interface.

PMID- 15470876
TI  - Immunohistochemical analysis of collagen fibrils within the hybrid layer: a
      FEISEM study.
AB  - This study evaluated the immunohistochemical labeling pattern of dentin collagen
      fibrils within hybrid layers created by different bonding systems using high
      resolution SEM. Four different adhesive materials, including self-etching and
      total-etching systems, were examined: Prime & Bond NT, OptiBond SOLO Plus, Single
      Bond and Clearfil Protect Bond. All materials were applied to the dentin of
      extracted human third molars. After cutting the bonded specimens transversely, an
      anti-collagen type I antibody was incubated on the surface of the dentin-adhesive
      interface and gold-conjugated secondary antibody was applied to reveal collagen
      labeling under high resolution SEM. The hybrid layers showed a significant number
      of collagen fibrils embedded in the resin matrix. The presence of exposed dentin
      collagen fibrils, as determined by positive labeling with an anti-type I collagen
      monoclonal antibody, is considered an indication of the presence of incompletely
      embedded fibrils and, thus, the quality of dentin matrix hybridization. The
      hybrid layers produced by total-etching systems showed higher labeling compared
      to those produced by the self-etching system. Positive collagen labeling was also
      found along the resin tags produced by total-etching adhesive systems.

PMID- 15470877
TI  - Effects of aging on mechanical properties of composite restoratives: a depth
      sensing microindentation approach.
AB  - This study investigated the effects of aging on the hardness and modulus of two
      composites (Tetric Ceram [TC], Vivadent; Esthet X [EX], Dentsply), a conventional
      (Compoglass [CG], Vivadent) and a posterior compomer (Dyract Posterior [DP],
      Dentsply) using a depth-sensing microindentation approach. Seven specimens (3-mm
      wide x 3-mm long x 2-mm deep) of each material were made and conditioned in
      distilled water at 37 degrees C. Hardness and modulus of the materials were
      determined at seven and 30 days using depth-sensing microindentation testing with
      the Instron MicroTester. Hardness was determined by dividing the peak load over
      the maximum projected contact area while effective modulus was calculated by
      analysis of the loading/unloading P-h curves and the analytical model according
      to Oliver and Pharr (1992). Results were analyzed using one-way ANOVA/Scheffe's
      post-hoc test and Independent Samples t-test at significance level 0.05. Mean
      Vickers Hardness (HV) ranged from 46.60 to 58.67 and 44.44 to 59.41 at seven and
      30 days, respectively. Mean indentation modulus ranged from 9.57 to 9.95 and 9.19
      to 10.03 for the same time periods. At both time periods, EX was significantly
      harder than all the other materials and HV values for TC were significantly
      greater than CG. No significant difference in hardness and modulus was observed
      between seven and 30 days for all materials with the exception of CG. For the
      latter, a significant decrease in mechanical properties was detected over time.

PMID- 15470878
TI  - Influence of environmental conditions on dentin bond strengths of one-application
      adhesive systems.
AB  - Resin composites are considered susceptible to environmental conditions that
      might affect bond strength. This study investigated the influence of relative
      humidity and temperature on the dentin bond strength of newly developed one
      application adhesive systems. Bonding systems employed in this study were five
      commercial one-application adhesive systems. Labial surfaces of bovine incisors
      were ground wet on 600-grit SiC paper. The teeth were transferred to a controlled
      temperature and humidity chamber and the specimens were prepared in six different
      environmental conditions, A) 25 +/- 0.5 degrees C, 50 +/- 5% RH, B) 25 +/- 0.5
      degrees C, 80 +/- 5% RH, C) 25 +/- 0.5 degrees C, 95 +/- 5% RH, D) 37 +/- 0.5
      degrees C, 50 +/- 5% RH, E) 37 +/- 0.5 degrees C, 80 +/- 5% RH, F) 37 +/- 0.5
      degrees C, 95 +/- 5% RH. The dentin surfaces were treated according to each
      manufacturer's instructions. Resin composites of each bonding system were
      condensed into a mold and light irradiated. After storage in 37 degrees C water
      for 24 hours, 10 specimens per group were tested in a shear mode in a testing
      machine at a crosshead speed of 1.0 mm/minute. Statistical analysis was carried
      out with one-way ANOVA followed by Duncan's multiple range tests at a p-value of
      0.05. The dentin bond strengths of one-application adhesive systems decreased
      with increasing RH. These data suggest that the relative high humidity in the
      oral environment needs consideration in developing clinical procedures for
      management of these one-application adhesive systems.

PMID- 15470879
TI  - Partial ceramic crowns: influence of preparation design and luting material on
      internal adaptation.
AB  - The influence of three different cavity preparations on the marginal integrity of
      partial ceramic crowns (PCC) luted with four different luting systems was
      investigated in this in vitro study. PCC preparations were performed in 144
      extracted human molars using one of the following preparation designs
      (n=48/preparation): A--Coverage of functional cusps/butt joint preparation; B-
      horizontal reduction of functional cusps and C--complete reduction of functional
      cusps/butt joint preparation. Non-functional cusps were not covered; mesial and
      distal proximal boxes were extended 1 mm below the cemento-enamel-junction. PCC
      were fabricated from Vita Mark II ceramic (Vita) with a Cerec 3 Unit (Sirona) and
      adhesively luted to the cavities using the following luting systems: (VL)
      Variolink II/Excite (Vivadent), (PA) Panavia F/ED Primer (Kuraray), (DY)
      Dyract/Prime & Bond NT (DeTrey/Dentsply) and (FU) Fuji Plus/GC Cavity Conditioner
      (GC). Samples were simultaneously exposed to thermocycling and mechanical loading
      (TC: 5000x8-55 degrees C, 30 seconds/cycle; ML: 500000x72.5N, 1.6Hz). Marginal
      adaptation was assessed by evaluating dye penetration on multiple sections by
      relating the actual penetration distance to the maximal length of the
      corresponding cavity wall (100%). Ceramic- and tooth-luting material interfaces
      were evaluated separately. The data were statistically analyzed with the Mann
      Whitney U-test and Wilcoxon Rank Sumtest. In general, no significant differences
      could be found between preparations A, B and C. The combination of preparation C
      and luting material PA showed a tendency for the lowest dye penetration values,
      especially within dentin (30%). Significant differences could be determined
      between luting materials: Composite luting materials PA (0%) and VL (1%) revealed
      less dye penetration than the compomer DY (6%) and resin-modified glass ionomer
      cement (RMGIC) FU (26%); use of RMGIC caused fractures of the restorations. The
      dentin/luting material interface showed the highest penetration values, ranging
      from 17% to 100%. In conclusion, with adhesively bonded partial ceramic crowns,
      the choice of luting material proved to be more relevant than preparation design
      under the limitations of this study. Margins below the cemento-enamel junction
      reveal significant loss of adhesion in spite of subsequent application of
      adhesive luting techniques. RMGIC cannot be recommended as a luting material for
      feldspathic PCC.

PMID- 15470880
TI  - Analysis of the degree of conversion of LED and halogen lights using micro-Raman
      spectroscopy.
AB  - This study determined the degree of conversion of two LED (light-emitting diodes)
      (Elipar FreeLight [FL], 3M ESPE; GC e-Light [EL], GC), a high intensity (Elipar
      TriLight [TL], 3M ESPE) and a very high intensity (Astralis 10 [AS], Ivoclar
      Vivadent) halogen light. The degree of conversion of these lights was compared to
      a conventional halogen light (Max [MX] (control), Dentsply-Caulk). Ten different
      light curing regimens, including pulse (EL1), continuous (FL1, EL2, TL1), turbo
      (EL3, AS1) and soft-start (FL2, EL4, TL2) modes of various lights were also
      investigated. Composite specimens of dimensions 3 x 3 x 2 mm were cured with the
      10 different light curing regimens investigated. Micro-Raman spectroscopy was
      used to determine the degree of conversion at the top and bottom surfaces of a
      composite restorative (Z100, [3M ESPE]) at 60 minutes post-light polymerization.
      Five specimens were made for each cure mode. The results were analyzed using
      ANOVA/Scheffe's post-hoc test and Independent Samples t-tests at significance
      level 0.05. The degree of conversion ranged from 55.98 +/- 2.50 to 59.00 +/-
      2.76% for the top surface and 51.90 +/- 3.36 to 57.28 +/- 1.56% for the bottom
      surface. No significant difference in degree of conversion was observed for the
      10 light curing regimens when compared to MX (control). The curing efficiency of
      LED lights was comparable to halogen lights regardless of curing modes.

PMID- 15470881
TI  - Demineralization inhibition of direct tooth-colored restorative materials.
AB  - This study compared the demineralization inhibition properties of fluoride
      releasing tooth-colored restorative materials. Materials evaluated included a
      giomer (Reactmer, Shofu [RM]), a conventional glass ionomer (Fuji II, GC [FJ]), a
      resin modified glass ionomer (Fuji II LC, GC [FL]) and a compomer (Dyract AP,
      Dentsply [DY]). A non-fluoride releasing composite (Spectrum TPH, Dentsply [SP])
      was used for comparison. Class V preparations on buccal and palatal/lingual were
      made at the CEJ of 75 freshly extracted molars. The teeth were randomly divided
      into five groups of 15 and restored with the various materials. The occlusal half
      of each restoration was in enamel, while the gingival half was in dentin. The
      restored teeth were stored in distilled water at 37 degrees C for two weeks and
      subjected to artificial caries challenge (18 hours demineralization [pH 5.0]
      followed by six hours of remineralization [pH 7.0]) for three days. Sections of
      130 +/- 20 microm were examined with a polarized light microscope, and outer
      lesion depth [OLD] and wall area [WA] lesion/inhibition measurements were made
      using image analysis software. All data were subjected to statistical analyses at
      0.05 significance level. For the various materials, OLD ranged from 54.55 to
      65.86 microm and 124.68 to 145.97 microm in enamel and dentin, respectively. WA
      ranged from -2356.13 to 1398.20 microm2 and -3011.73 to 5095.80 microm2 (positive
      values indicate wall inhibition, negative values indicate wall lesion) in enamel
      and dentin, respectively. Results of ANOVA/Scheffe's post-hoc test (p<0.05) were
      as follows: Enamel OLD--no significant difference between materials; Dentin OLD-
      SP > FJ, FL & RM; Enamel WA inhibition--FJ, FL & RM > DY & SP and Dentin WA
      inhibition--FJ > FL > RM > DY > SP. The demineralization inhibition effect of
      giomers, conventional and resin-modified glass ionomer cements appear to be more
      evident at the margins of restorations.

PMID- 15470882
TI  - Effects of pH on the surface texture of glass ionomer based/containing
      restorative materials.
AB  - This study determined the effect of pH on the surface texture of commonly used
      posterior glass-ionomer based/containing restorative materials. The materials
      evaluated included a compomer (Dyract AP), a giomer (Beautifil) and two highly
      viscous glass ionomer cements (Fuji IX and Ketac Molar). A resin composite
      (Esthet-X) was used for comparison. Forty-two specimens (3-mm wide x 3-mm long x
      2-mm deep) were made for each material. The specimens were divided into six
      groups and conditioned in the following solutions at 37 degrees C for one week:
      Citric acid (pH 2, 3, 4, 5 and 6) and distilled water (pH 7). After conditioning,
      the surface roughness (Ra, microm) of each specimen was measured using a surface
      profilometer (Surftest, Mitutoyo Corp, Tokyo, Japan). Data was analyzed using one
      way ANOVA and Scheffe's test at a significance level of 0.05. The effects of pH
      on the surface texture of glass-ionomer based/containing restoratives were
      material dependent. Ra values ranged from 0.02 microm to 0.15 microm and 0.03
      microm to 4.40 microm for pH 7 and 2, respectively. With the exception of the
      composite, the surface roughness of all materials evaluated was significantly
      affected by acids of low pH. The surface texture of highly viscous glass ionomer
      cements deteriorated significantly when conditioned in solutions of low pH, which
      makes them more susceptible to clinical failure.

PMID- 15470883
TI  - Stability of dentin bond strengths using different bonding techniques after 12
      months: total-etch, deproteinization and self-etching.
AB  - This study evaluated the influence of (1) different dentin treatments and (2)
      storage time on dentin shear bond strengths. Two hundred and twenty-five bovine
      incisors were collected, ground to expose a flat dentin surface and randomly
      divided into three groups according to dentin surface treatment: (1) Total etch +
      Single Bond; (2) Total etch + collagen depletion with 10% NaOCl + Single Bond and
      (3) No etch + experimental self-etching adhesive. Composite was applied to the
      treated surfaces using a 3 x 5 mm cylindrical Teflon matrix and was light-cured.
      Each group was further stratified in five subgroups according to storage time in
      water at 37 degrees C: 1 day, 7 days, 30 days, 6 months and 12 months. Shear bond
      strengths (SBS) were determined and expressed in MPa. Data was analyzed for
      statistical significance with two-way ANOVA and Tukey's test (p=0.05). No
      interaction was observed between surface treatment and storage time. Storage time
      did not significantly affect bond strengths. Statistically significant
      differences were observed among the different surface treatments. Single Bond
      applied after total-etch presented higher mean SBS when compared to the other
      surface treatment methods. Collagen removal negatively influenced SBS, and the
      experimental self-etching adhesive presented intermediate values.

PMID- 15470884
TI  - Agricultural biotechnology. A growing field.

PMID- 15470885
TI  - Cloning vectors for expression-PCR products.

PMID- 15470887
TI  - Shuffled: a software suite that assists the analysis of recombinant products
      resulting from DNA shuffling.

PMID- 15470888
TI  - Robust dosage (RD)-PCR protocol for the detection of heterozygous deletions.

PMID- 15470886
TI  - Universal method for producing ROX-labeled size standards suitable for automated
      genotyping.

PMID- 15470889
TI  - Scalable high-throughput micro-expression device for recombinant proteins.

PMID- 15470890
TI  - Robust expression of transgenes in MCF-7 breast cancer cells is expression vector
      dependent.

PMID- 15470891
TI  - Polyhydroxybutyrate-enhanced transformation of log-phase Escherichia coli.
AB  - Transformation of Escherichia coli plays an important role in recombinant DNA
      technology. Most current transformation protocols require that the cells be
      treated to attain a particular physiological state known as "competence," and
      this makes transformation procedures lengthy and arduous. Here we describe a
      protocol for transforming log-phase E. coli using dimethyl sulfoxide (DMSO)
      solutions of poly-(R)-3-hydroxybutyrate (PHB) to facilitate the transfer of
      plasmid DNA into cells, and certain reagents and temperature shocks to promote
      DNA uptake. The protocol was optimized using factorial design techniques across
      variables that included PHB molecular weight and concentration, DMSO
      concentration, monovalent and divalent salts, glucose, cold and heat shocks, cell
      density, and pH. Using 10 ng DNA, the optimized protocol produces approximately
      1000 colony-forming units (CFUs) from 100 microL early log-phase cell culture or
      approximately 300 CFU from a 21-24 h single colony, sufficient for many
      applications. The total volume of the transformation reaction mixture is only 150
      microL suggesting that the procedure may be adapted for use in microplates or
      automated transformation technologies.

PMID- 15470892
TI  - Development of a universal gap repair vector for yeast-based screening of
      knockout rodents.
AB  - Recently, we reported the production of the first knockout rats by combining N
      ethyl-N-nitrosourea (ENU)-induced mutagenesis with a yeast-based truncation
      screening method. To make this new knockout technology more applicable for other
      laboratories and for high-throughput applications, we have developed a universal
      gap repair vector that is ready for use in screening for gene knockouts without
      additional engineering. The universal gap repair vector was validated for its
      application in both cDNA- and genomic DNA-based yeast truncation mutation assays.
      Breast cancer genes Brca1, Brca2, and Adenomatosis polyposis coli (Apc) genes
      from N2 rats of Brca1 and Brca2 knockouts and (Atm x ApcMin/+)F1 mice were
      examined, respectively. The results indicate that the universal gap repair vector
      we developed, using randomly selected codons as a universal cassette, is equally
      efficient at identifying truncation mutations as are those gap repair vectors
      designed specifically for Brca1 and Brca2. The availability of a universal gap
      repair vector should facilitate the broader screening of knockouts of most genes
      of many species using the combined approach of ENU-induced mutagenesis and yeast
      truncation assay.

PMID- 15470893
TI  - Mutation detection using ligase chain reaction in passivated silicon-glass
      microchips and microchip capillary electrophoresis.
AB  - The ligase chain reaction (LCR) following PCR is one of the most sensitive and
      specific methods for detecting mutations, especially single nucleotide
      polymorphisms (SNPs). Performing LCR in microchips remains a challenge because of
      the inhibitory effect of the internal surfaces of silicon-glass microchips. We
      have tested a dynamic polymer-based surface passivation method for LCR conducted
      in oxide-coated silicon-glass microchips. The combination of polyvinylpyrrolidone
      40 (PVP-40) at 0.75% (w/v) with an excess of the ligase produced successful LCR
      in the silicon-glass microchips, with yields of ligated primers comparable to
      reactions performed in conventional reaction tubes. Ligated primers were detected
      and quantified simply and conveniently using microchip capillary electrophoresis.

PMID- 15470894
TI  - Multiplex ligation-dependent probe amplification using a completely synthetic
      probe set.
AB  - The recent development of multiplex ligation-dependent probe amplification (MLPA)
      has provided an efficient and reliable assay for dosage screening of multiple
      loci in a single reaction. However, a drawback to this method is the time
      consuming process of generating a probe set by cloning in single-stranded
      bacteriophage vectors. We have developed a synthetic probe set to screen for
      deletions in a region spanning 18.5 Mb within chromosome 3q. In a pilot study, we
      tested 15 synthetic probes on 4 control samples and on 2 patients previously
      found to possess a heterozygous deletion in the region 3q26-q28. These synthetic
      probes detected deletions at all previously known deleted loci. Furthermore,
      using synthetic probes, the variability of results within samples was similar to
      that reported for commercially available M13-derived probes. Our results
      demonstrate that this novel approach to MLPA provides a generic solution to the
      difficulties of probe development by cloning; such synthetically generated probes
      may be used to screen a large number of loci in a single reaction. We conclude
      that the use of synthetic probes for MLPA is a rapid, robust, and efficient
      alternative for research (and potentially diagnostic) deletion and duplication
      screening of multiple genomic loci.

PMID- 15470895
TI  - Inaccuracies in MTS assays: major distorting effects of medium, serum albumin,
      and fatty acids.
AB  - Soluble formazan assays are widely used for cell number assessment. However, in
      our hands, we observed frequent occasions in which the actual cell number was at
      odds with the assay reading. In this study, we have determined that (i) a large
      proportion of the reading obtained in commonly used culture media can be caused
      by media component amplification of formazan production in a way that cannot be
      corrected for by media-only controls; (ii) the albumin present in 10% serum can
      reduce the assay absorbance by 50% so that an actual doubling of cell number can
      be obscured; and (iii) this latter effect is dependent on the concentration of
      fatty acids. To counter these problems, we have developed a protocol that gives
      consistent readings that are fully representative of cell number while retaining
      some of the original advantages of soluble formazan assays.

PMID- 15470896
TI  - Detection of bacterial endotoxin in human tissues.
AB  - Detection of bacterial lipopolysaccharide (LPS) in the absence of overt infection
      is a challenging problem in tissue homogenates and other complex samples. We
      found that conventional Limulus amebocyte lysate (LAL) assays are not suitable
      for this purpose due to interference from beta-glucan-like molecules. In
      contrast, a modified LAL assay that is unaffected by beta-glucan-like molecules
      was able to detect LPS in infected tissue and in a subset of clinically aseptic
      tissues. A two-step LAL assay was used to exclude the possibility of false
      positives due to nonspecific amidases. False positives due to sample color were
      also excluded, as were false negatives due to assay inhibition. This is the first
      report to successfully detect LPS in tissue in the absence of overt infection.
      This approach may be extremely useful in assessing recent hypotheses that
      subclinical levels of bacteria contribute to a wide range of chronic diseases.

PMID- 15470897
TI  - Method for enhancing solubility of the expressed recombinant proteins in
      Escherichia coli.
AB  - The production of correctly folded protein in Escherichia coli is often
      challenging because of aggregation of the overexpressed protein into inclusion
      bodies. Although a number of general and protein-specific techniques are
      available, their effectiveness varies widely. We report a novel method for
      enhancing the solubility of overexpressed proteins. Presence of a dipeptide,
      glycylglycine, in the range of 100 mM to 1 M in the medium was found to
      significantly enhance the solubility (up to 170-fold) of the expressed proteins.
      The method has been validated using mycobacterial proteins, resulting in improved
      solubilization, which were otherwise difficult to express as soluble proteins in
      E. coli. This method can also be used to enhance the solubility of other
      heterologous recombinant proteins expressed in a bacterial system.

PMID- 15470898
TI  - Producing peptide arrays for epitope mapping by intein-mediated protein ligation.
AB  - Peptide arrays are increasingly used to define antibody epitopes and substrate
      specificities of protein kinases. Their use is hampered, however, by ineffective
      and variable binding efficiency of peptides, which often results in low
      sensitivity and inconsistent results. To overcome these limitations, we have
      developed a novel method for making arrays of synthetic peptides on various
      membranes after ligating the peptide substrates to an intein-generated carrier
      protein. We have conducted screening for optimal carrier proteins by
      immunoreactivity and direct assessment of binding using a peptide derivatized at
      a lysine sidechain with fluorescein, CDPEK(fluorescein)DS. Ligation of a
      synthetic peptide antigen to a carrier protein, HhaI methylase, resulted in an
      improved retention of peptides and an increased sensitivity of up to 10(4)-fold
      in immunoassay- and epitope-scanning experiments. Denaturing the ligation
      products with 2% sodium dodecyl sulfate (SDS) or an organic solvent (20%
      methanol) prior to arraying did not significantly affect the immunoreactivity of
      the HhaI methylase-peptide product. Because the carrier protein dominates the
      binding of ligation products and contains one peptide reactive site, the amount
      of peptide arrayed onto the membranes can be effectively normalized. This
      technique was utilized in the alanine scanning of hemagglutinin (HA) antigen
      using two monoclonal antibodies, resulting in distinguishing the different
      antigen epitope profiles. Furthermore, we show that this method can be used to
      characterize the antibodies that recognize phosphorylated peptides. This novel
      approach allows for synthetic peptides to be uniformly arrayed onto membranes,
      compatible with a variety of applications.

PMID- 15470899
TI  - Transfection microarray of nonadherent cells on an oleyl poly(ethylene glycol)
      ether-modified glass slide.
AB  - Cell-based microarrays are emerging as a tool for analyzing the functions of
      genes in cells. However, partly due to the difficulty of cell immobilization, the
      application of this method has been limited to adherent cells. We previously
      reported a method that rapidly and strongly attached living nonadherent cells to
      glass slides modified with a cell membrane anchoring reagent, designated a
      biocompatible anchor for membrane (BAM). Here we demonstrate that plasmid DNA
      deposited in a defined area on BAM-modified glass slides was transfected into
      nonadherent K562 cells immobilized on the DNA-deposited and BAM-modified slides.
      This method allowed the transfection of K562 cells not only with plasmid cDNA
      expression vectors but also with small interfering RNA (siRNA) at a defined
      location on the BAM-modified slides. We expect this methodology to greatly expand
      the scope of current cell microarray technology.

PMID- 15470900
TI  - siRNA cell arrays for high-content screening microscopy.
AB  - RNA interference (RNAi) is a recent advance that provides the possibility to
      reduce the expression of specific target genes in cultured mammalian cells with
      potential applications on a genome-wide scale. However, to achieve this, robust
      methodologies that allow automated and efficient delivery of small interfering
      RNAs (siRNAs) into living cultured cells and reliable quality control of siRNA
      function must be in place. Here we describe the production of cell arrays for
      reverse transfection of tissue culture cells with siRNA and plasmid DNA suitable
      for subsequent high-content screening microscopy applications. All the necessary
      transfection components are mixed prior to the robotic spotting on noncoated
      chambered coverglass tissue culture dishes, which are ideally suited for time
      lapse microscopy applications in living cells. The addition of fibronectin to the
      spotting solution improves cell adherence. After cell seeding, no further cell
      culture manipulations, such as medium changes or the addition of 7 serum, are
      needed. Adaptation of the cell density improves autofocus performance for high
      quality data acquisition and cell recognition. The co-transfection of a
      nonspecific fluorescently labeled DNA oligomer with the specific siRNA helps to
      mark each successfully transfected cell and cell cluster. We demonstrate such an
      siRNA cell array in a microscope-based functional assay in living cells to
      determine the effect of various siRNA oligonucleotides against endogenous targets
      on cellular secretion.

PMID- 15470901
TI  - Universal mouse reference RNA derived from neonatal mice.
AB  - A reproducible, transcriptionally diverse common reference RNA is required for
      accurate comparisons of data generated from most spotted microarray experiments
      in different experiments. Several methods have been proposed to make such a
      reference RNA, such as pooling RNAs isolated from multiple cell lines or tissues,
      amplifying pooled RNAs, or synthesizing RNAs or DNAs complementary to microarray
      features. We report an approach to prepare a large amount of mouse reference RNA
      from whole neonatal mice. This approach is simple, quick, reliable, reproducible,
      and inexpensive. The whole mouse reference RNA is highly representative when
      compared to two commercially available universal mouse reference RNAs isolated
      and pooled from multiple cell lines or organs.

PMID- 15470902
TI  - Suitability of stratagene reference RNA for analysis of lymphoid tissues.
AB  - We evaluated a lymphoid RNA standard prepared in our laboratory for spotted
      microarrays against the Universal Human Reference standard from Stratagene. Our
      goal was to determine if the Stratagene standard, which contains only two
      lymphoid cell lines out of a pool of 10 human cancer cell lines, had acceptable
      gene coverage to serve as a comprehensive standard for gene expression profiling
      of lymphoid tissues. Our lymphoid standard was prepared from thymus, spleen,
      tonsil, and cell lines representing immature B cells, plasma cells, and natural
      killer (NK) cells, thus covering the entire spectrum of lymphoid cells and most
      stromal elements present in specialized lymphoid tissues. The two standards were
      co-hybridized on oligonucleotide microarrays containing 17,260 genes, and both
      had fluorescence intensities above background for approximately 85% of the genes.
      Despite the limited representation of lymphoid cells in the Stratagene standard,
      only 4.2% genes exhibited expression differences greater than 2-fold including
      only 0.35% with differences greater than 4-fold. Although the lymphoid standard
      reflected a more comprehensive representation of immune system-associated genes,
      the Stratagene standard has the advantage of being commercially available,
      enabling easier comparison across laboratories and allowing comparative studies
      across a long period of time.

PMID- 15470903
TI  - Multiparametric duplex real-time nucleic acid sequence-based amplification assay
      for mRNA profiling.
AB  - Nucleic acid sequence-based amplification (NASBA) is a sensitive isothermal
      transcription-based amplification method. We have developed real-time NASBA
      assays to detect mRNA coding for the estrogen receptor alpha (ESR1) and the
      progesterone receptor (PGR) in breast tumors by means of duplex reactions using
      cyclophilin B (PPIB) as the normalizing gene. Both the ESR1/PPIB and PGR/PPIB
      duplex NASBA assays are highly sensitive, specific, and reproducible.
      Quantification is determined using external standard calibration curves and the
      ratio between the number of target and housekeeping gene mRNA copies.
      Amplification of the target gene in the duplex NASBA assay was disrupted when
      this latter was mixed with a large amount of the housekeeping PPIB gene,
      suggesting that it is preferable for the normalizing gene chosen to have an
      expression level comparable to the target gene. Sensitivity and robustness of the
      duplex NASBA assays were assessed in breast cancer cell lines. Such a rapid and
      easy-to-use multiparametric duplex real-time NASBA assay could also
      advantageously be set up for other mRNA profiling applications.

PMID- 15470904
TI  - PPARs: altering clinical responses in Type 2 diabetes and atherosclerosis.
      Introduction.

PMID- 15470905
TI  - Will the potential of peroxisome proliferator-activated receptor agonists be
      realized in the clinical setting?
AB  - Drugs targeting both peroxisome proliferator-activated receptor-gamma (PPAR
      gamma) agonists (the thiazolidinediones) and PPAR-alpha (the fibrates) have
      already been developed for clinical use. However, the thiazolidinediones,
      currently prescribed to treat hyperglycemia and improve peripheral insulin
      resistance, may also have cardiovascular benefits that have yet to be fully
      realized. Animal models of atherosclerosis have shown that the thiazolidinediones
      reduce the extent of atherosclerotic lesions and inhibit macrophage accumulation.
      Clinical studies have also shown that these drugs improve the lipid profile of
      patients at risk of developing atherosclerosis and reduce circulating levels of
      inflammatory markers. This combination of lower lipid concentrations and reduced
      inflammation may explain the cardiovascular benefits of this class of drugs.
      Early trials in patients with coronary stents have reported promising findings,
      with restenosis rates being greatly reduced with thiazolidinedione therapy. It is
      hoped that the results of future clinical trials will continue to be encouraging,
      so that the thiazolidinediones' cardiovascular benefits can be fully realized in
      the clinic.

PMID- 15470906
TI  - What are the effects of peroxisome proliferator-activated receptor agonists on
      adiponectin, tumor necrosis factor-alpha, and other cytokines in insulin
      resistance?
AB  - Patients with type 2 diabetes are at high risk of cardiovascular disease. In
      addition to treating hyperglycemia, the thiazolidinedione (TZD) class of
      antidiabetic agents may also benefit the cardiovascular complications associated
      with the disease. The two available TZDs, pioglitazone and rosiglitazone, are
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists that
      influence gene expression of key proteins involved in regulating glucose and
      lipid metabolism. Tumor necrosis factor-alpha (TNF-alpha) and adiponectin are
      believed to be important in the development of insulin resistance and
      atherosclerosis. Understanding the role of these cytokines in the inflammatory
      processes that trigger plaque development might lead to identification of other
      potential mechanisms that could be exploited to enhance future treatments for
      patients with diabetes and atherosclerosis.

PMID- 15470907
TI  - Imaging and peroxisome proliferator-activated receptor agonists: uncovering their
      role in atherosclerosis development.
AB  - Technologic advances have enhanced clinical understanding of the physical changes
      that occur in the vasculature during atherosclerosis development. Traditionally,
      diagnostic techniques such as angiography have focused on the lumen of the
      coronary arteries, with narrowing of the lumen suggesting the presence of
      atherosclerotic plaques in the vessel wall. Newer methods, such as intravascular
      ultrasound, focus on the vessel wall itself and have shown that extensive plaque
      development can occur in conjunction with minimal luminal restriction of the
      artery. In fact, lumen narrowing occurs only in the very late stages of
      atherosclerosis, suggesting that, in many cases, the early stages of disease
      development would remain undetected when angiographic techniques are used. The
      ability to detect atheromatous disease, particularly in the early stages of
      development, must be accompanied by systemic pharmacologic therapies effective in
      inducing atherosclerotic regression. With this in mind, a recent study in
      patients treated with statins has shown less progression with aggressive lipid
      lowering, while the findings from trials employing peroxisome proliferator
      activated receptor-gamma agonists are eagerly awaited.

PMID- 15470908
TI  - Variations in dose response with x-ray energy of LiF:Mg,Cu,P thermoluminescence
      dosimeters: implications for clinical dosimetry.
AB  - In many medical procedures where accurate radiation dose measurements are needed,
      the variation of detector response with x-ray energy is of concern. The response
      of LiF:Mg,Cu,P TLDs to a range of x-ray energies was analysed in monoenergetic
      (synchrotron), diagnostic and therapy radiation beams with the aim of
      implementing this dosimeter into clinical practice where existing dosimetry
      techniques are limited due to lack of sensitivity or tissue equivalence (e.g.
      neonatal radiography, mammography and brachytherapy). LiF:Mg,Cu,P TLDs in
      different forms from two manufacturers (MCP-N: TLD Poland, GR200: SDDML China)
      were irradiated using x-ray beams covering 10 keV to 18 MVp. Dose readings were
      compared with an ionization chamber. The effect of different TLD types and
      annealing cycles on clinical utility was investigated. The measured energy
      response of LiF:Mg,Cu,P TLDs was fit to a simple model devised by Kron et al
      (1998 Phys. Med. Biol. 43 3235-59) to describe the variation of TLD response with
      x-ray energy. If TLDs are handled as recommended in the present paper, the energy
      response of LiF:Mg,Cu,P deviates by a maximum of 15% from unity and agrees with
      the model to within 5% or experimental uncertainty between 15 keV and 10 MeV.
      LiF:Mg,Cu,P TLDs of all forms have consistent and superior energy response
      compared to the standard material LiF:Mg,Ti and are therefore suitable for a wide
      range of applications in diagnostic radiology and radiotherapy.

PMID- 15470909
TI  - Linear energy transfer dependence of a normoxic polymer gel dosimeter
      investigated using proton beam absorbed dose measurements.
AB  - Three-dimensional dosimetry with good spatial resolution can be performed using
      polymer gel dosimetry, which has been investigated for dosimetry of different
      types of particles. However, there are only sparse data concerning the influence
      of the linear energy transfer (LET) properties of the radiation on the gel
      absorbed dose response. The purpose of this study was to investigate possible LET
      dependence for a polymer gel dosimeter using proton beam absorbed dose
      measurements. Polymer gel containing the antioxidant
      tetrakis(hydroxymethyl)phosphonium (THP) was irradiated with 133 MeV
      monoenergetic protons, and the gel absorbed dose response was evaluated using
      MRI. The LET distribution for a monoenergetic proton beam was calculated as a
      function of depth using the Monte Carlo code PETRA. There was a steep increase in
      the Monte Carlo calculated LET starting at the depth corresponding to the front
      edge of the Bragg peak. This increase was closely followed by a decrease in the
      relative detector sensitivity (Srel = Dgel/Ddiode), indicating that the response
      of the polymer gel detector was dependent on LET. The relative sensitivity was
      0.8 at the Bragg peak, and reached its minimum value at the end of the proton
      range. No significant effects in the detector response were observed for LET <
      4.9 keV microm(-1), thus indicating that the behaviour of the polymer gel
      dosimeter would not be altered for the range of LET values expected in the case
      of photons or electrons in a clinical range of energies.

PMID- 15470910
TI  - Analysis of stochastic noise in intensity-modulated beams.
AB  - Inverse planning techniques are known to produce intensity-modulated beams (IMBs)
      that are highly modulated. They are characterized by the fact that they contain
      high-frequency modulations that are absent in the profiles that are easier to
      deliver. For the purpose of this study these clinically unwanted fluctuations are
      being defined as 'noise'. Although these highly modulated solutions are also
      optimal solutions, as soon as the profiles are being delivered, they become
      unfavourable with respect to delivery efficiency and the analysis and
      verification of treatment. The aim of this work was therefore to understand the
      origins of the structure and complexity of IMBs. Ultimately, if one can
      characterize the essential features in optimum beam profiles, it might be
      possible to control the frequency distribution of IMBs and simplify the IMRT
      planning and delivery process. The study was based on two common optimization
      techniques: simulated annealing (SA) and gradient-descent (GD). The assumptions
      made at the start of this work were that the stochastic noise caused by the SA
      optimization technique is dominant over other sources of noise and that it could
      be separated out from the essential modulation after convergence of the cost
      function by averaging minimum-cost fluence profiles. The results indicate that
      there are three possible sources of stochastic noise in IMBs, i.e. the
      optimization technique, the cost function and the definition of convergence of
      that cost function. In terms of the optimization technique itself, it was
      confirmed that the gradient-descent technique does not introduce stochastic noise
      in the IMBs. The SA technique does introduce stochastic noise but averaging of
      minimum-cost fluence profiles does not result in smoother beam profiles. This
      originates from the fact that this type of noise is not the dominant factor in
      the optimization, but rather the curvature of the cost function close to the
      global minimum. It is shown that the choice of initial temperature in the SA
      optimization technique is crucial for the convergence of the cost function and
      the frequency distribution of the fluence profiles. If the initial temperature is
      too small the stochastic noise will get frozen into the fluence profiles and
      become the dominant component of noise, resulting in very random-looking and
      difficult to deliver patterns.

PMID- 15470911
TI  - The influence of head frame distortions on stereotactic localization and
      targeting.
AB  - A strong attachment of a stereotactic head frame to the patient's skull may cause
      distortions of the head frame. The aim of this work was to identify possible
      distortions of the head frame, to measure the degree of distortion occurring in
      clinical practice and to investigate its influence on stereotactic localization
      and targeting. A model to describe and quantify the distortion of the Riechert
      Mundinger (RM) head frame was developed. Distortions were classified as (a)
      bending and (b) changes from the circular ring shape. Ring shape changes were
      derived from stereotactic CT scans and frame bending was determined from
      intraoperative stereotactic x-ray images of patients with implanted 125I-seeds
      acting as landmarks. From the examined patient data frame bending was determined
      to be 0.74 mm+/-0.32 mm and 1.30 mm in maximum. If a CT-localizer with a top ring
      is used, frame bending has no influence on stereotactic CT-localization. In
      stereotactic x-ray localization, frame bending leads to an overestimation of the
      z-coordinate by 0.37 mm+/-0.16 mm on average and by 0.65 mm in maximum. The
      accuracy of patient positioning in radiosurgery is not affected by frame bending.
      But in stereotactic surgery with an RM aiming bow trajectory displacements are
      expected. These displacements were estimated to be 0.36 mm+/-0.16 mm (max. 0.74
      mm) at the target point and 0.65 mm+/-0.30 mm (max. 1.31 mm) at the entry point
      level. Changes from the circularring shape are small and do not compromise the
      accuracy of stereotactic targeting and localization. The accuracy of CT
      localization was found to be close to the resolution limit due to voxel size. Our
      findings for frame bending of the RM frame could be validated by statistical
      analysis and by comparison with an independent patient examination. The results
      depend on the stereotactic system and details of the localizers and instruments
      and also reflect our clinical practice. Therefore, a generalization is not
      possible. Preliminary experience with a new MR-compatible RM head frame made of
      ceramics shows no frame distortions as with the conventional frame made of an Al
      Cu-Mg alloy.

PMID- 15470912
TI  - X-ray micro-tomography system for small-animal imaging with zoom-in imaging
      capability.
AB  - Since a micro-tomography system capable of microm-resolution imaging cannot be
      used for whole-body imaging of a small laboratory animal without sacrificing its
      spatial resolution, it is desirable for a micro-tomography system to have local
      imaging capability. In this paper, we introduce an x-ray micro-tomography system
      capable of high-resolution imaging of a local region inside a small animal. By
      combining two kinds of projection data, one from a full field-of-view (FOV) scan
      of the whole body and the other from a limited FOV scan of the region of interest
      (ROI), we have obtained zoomed-in images of the ROI without any contrast
      anomalies commonly appearing in conventional local tomography. For experimental
      verification of the zoom-in imaging capability, we have integrated a micro
      tomography system using a microfocus x-ray source, a 1248 x 1248 flat-panel x-ray
      detector, and a precision scan mechanism. The mismatches between the two
      projection data caused by misalignments of the scan mechanism have been estimated
      with a calibration phantom, and the mismatch effects have been compensated in the
      image reconstruction procedure. Zoom-in imaging results of bony tissues with a
      spatial resolution of 10 lp mm(-1) suggest that zoom-in micro-tomography can be
      greatly used for high-resolution imaging of a local region in small-animal
      studies.

PMID- 15470913
TI  - A two-step Hilbert transform method for 2D image reconstruction.
AB  - The paper describes a new accurate two-dimensional (2D) image reconstruction
      method consisting of two steps. In the first step, the backprojected image is
      formed after taking the derivative of the parallel projection data. In the second
      step, a Hilbert filtering is applied along certain lines in the differentiated
      backprojection (DBP) image. Formulae for performing the DBP step in fanbeam
      geometry are also presented. The advantage of this two-step Hilbert transform
      approach is that in certain situations, regions of interest (ROIs) can be
      reconstructed from truncated projection data. Simulation results are presented
      that illustrate very similar reconstructed image quality using the new method
      compared to standard filtered backprojection, and that show the capability to
      correctly handle truncated projections. In particular, a simulation is presented
      of a wide patient whose projections are truncated laterally yet for which highly
      accurate ROI reconstruction is obtained.

PMID- 15470914
TI  - High resolution ultrasound elastomicroscopy imaging of soft tissues: system
      development and feasibility.
AB  - Research in elasticity imaging typically relies on 1-10 MHz ultrasound.
      Elasticity imaging at these frequencies can provide strain maps with a resolution
      in the order of millimetres, but this is not sufficient for applications to skin,
      articular cartilage or other fine structures. We developed a prototype high
      resolution elastomicroscopy system consisting of a 50 MHz ultrasound backscatter
      microscope system and a calibrated compression device using a load cell to
      measure the pressure applied to the specimen, which was installed between a
      rigidly fixed face-plate and a specimen platform. Radiofrequency data were
      acquired in a B-scan format (10 mm wide x 3 mm deep) in specimens of mouse skin
      and bovine patellar cartilage. The scanning resolution along the B-scan plane
      direction was 50 microm, and the ultrasound signals were digitized at 500 MHz to
      achieve a sensitivity better than 1 microm for the axial displacement
      measurement. Because of elevated attenuation of ultrasound at high frequencies,
      special consideration was necessary to design a face-plate permitting efficient
      ultrasound transmission into the specimen and relative uniformity of the
      compression. Best results were obtained using a thin plastic film to cover a
      specially shaped slit in the face-plate. Local tissue strain maps were
      constructed by applying a cross-correlation tracking method to signals obtained
      at the same site at different compression levels. The speed of sound in the
      tissue specimen (1589.8+/-7.8 m s(-1) for cartilage and 1532.4+/-4.4 m s(-1) for
      skin) was simultaneously measured during the compression test. Preliminary
      results demonstrated that this ultrasound elastomicroscopy technique was able to
      map deformations of the skin and articular cartilage specimens to high
      resolution, in the order of 50 microm. This system can also be potentially used
      for the assessment of other biological tissues, bioengineered tissues or
      biomaterials with fine structures.

PMID- 15470915
TI  - First photon detection in time-resolved transillumination imaging: a theoretical
      evaluation.
AB  - First photon detection, as a special case of time-resolved transillumination
      imaging, is studied through the derivation of the temporal probability density
      function (pdf) for the first arriving photon. The pdf for different laser
      intensities, media and second and later arriving photons were generated. The
      arrival time of the first detected photon reduced as the laser power increased
      and also when the scattering and absorption coefficients decreased. The pdf for
      an imbedded totally absorbing 3 mm inhomogeneity may be distinguished from the
      pdf of a homogeneous turbid medium similar to that of human breast in dimensions
      and optical properties.

PMID- 15470916
TI  - Spectral components of laser Doppler flowmetry signals recorded in healthy and
      type 1 diabetic subjects at rest and during a local and progressive cutaneous
      pressure application: scalogram analyses.
AB  - A significant transient increase in laser Doppler flowmetry (LDF) signals is
      observed in response to a local and progressive cutaneous pressure application in
      healthy subjects. This reflex may be impaired in diabetic patients. The work
      presents a signal processing providing the clarification of this phenomenon.
      Scalogram analyses of LDF signals recorded at rest and during a local and
      progressive cutaneous pressure application are performed on healthy and type 1
      diabetic subjects. Three frequency bands, corresponding to myogenic, neurogenic
      and endothelial related metabolic activities, are studied. The results show that,
      at rest, the scalogram energy of each frequency band is significantly lower for
      diabetic patients than for healthy subjects, but the scalogram relative energies
      do not show any statistical difference between the two groups. Moreover, the
      neurogenic and endothelial related metabolic activities are significantly higher
      during the progressive pressure than at rest, in healthy and diabetic subjects.
      However, the relative contribution of the endothelial related metabolic activity
      is significantly higher during the progressive pressure than at rest, in the
      interval 200-400 s following the beginning of the pressure application, but only
      for healthy subjects. These results may improve knowledge on cutaneous
      microvascular responses to injuries or local pressures initiating diabetic
      complications.

PMID- 15470917
TI  - A stochastic model simulating the capture of pathogenic micro-organisms by
      superparamagnetic particles in an isodynamic magnetic field.
AB  - The method of immunomagnetic separation (IMS) has become an established technique
      to concentrate and separate animal cells, biologically active compounds and
      pathogenic micro-organisms from clinical, food and environmental matrices. One
      drawback of this technique is that the analysis is only possible for small sample
      volumes. We have developed a stochastic model that involves numerical simulations
      to optimize the process of concentration of pathogenic micro-organisms onto
      superparamagnetic carrier particles (SCPs) in a gradient magnetic field. Within
      the range of the system parameters varied in the simulations, optimal conditions
      favour larger particles with higher magnetite concentrations. The dependence on
      magnetic field intensity and gradient together with concentration of particles
      and micro-organisms was found to be less important for larger SCPs but these
      parameters can influence the values of the collision time for small particles.
      These results will be useful in aiding the design of apparatus for immunomagnetic
      separation from large volume samples.

PMID- 15470918
TI  - Photon migration in turbid media with anisotropic optical properties.
AB  - We analyse properties of photon migration in reflectance measurements made on a
      semi-infinite medium bounded by a plane, in which optical parameters may vary in
      directions neither parallel to, nor perpendicular to the bounding plane. Our aim
      in doing this is to develop the formulae necessary to deduce parameters of
      directionality from both time-gated and continuous wave measurements. The
      mathematical development is based on a diffusion picture, in which the bounding
      plane is regarded as being totally absorbing so that all photons reaching the
      surface contribute to the reflectance.

PMID- 15470919
TI  - Methodology for lognormal modelling of malignant pleural mesothelioma survival
      time distributions: a study of 5580 case histories from Europe and USA.
AB  - A truncated left-censored and right-censored lognormal model has been validated
      for representing pleural mesothelioma survival times in the range 5-200 weeks for
      data subsets grouped by age for males, 40-49, 50-59, 60-69, 70-79 and 80+ years
      and for all ages combined for females. The cases available for study were from
      Europe and USA and totalled 5580. This is larger than any other pleural
      mesothelioma cohort accrued for study. The methodology describes the computation
      of reference baseline probabilities, 5-200 weeks, which can be used in clinical
      trials to assess results of future promising treatment methods. This study is an
      extension of previous lognormal modelling by Mould et al (2002 Phys. Med. Biol.
      47 3893-924) to predict long-term cancer survival from short-term data where the
      proportion cured is denoted by C and the uncured proportion, which can be
      represented by a lognormal, by (1 - C). Pleural mesothelioma is a special case
      when C = 0.

PMID- 15470920
TI  - Inclusion of organ movements in IMRT treatment planning via inverse planning
      based on probability distributions.
AB  - In this paper, we investigate an off-line strategy to incorporate inter-fraction
      organ motion in IMRT treatment planning. It was suggested that inverse planning
      could be based on a probability distribution of patient geometries instead of a
      single snap shot. However, this concept is connected to two intrinsic problems:
      first, this probability distribution has to be estimated from only a few images;
      and second, the distribution is only sparsely sampled over the treatment course
      due to a finite number of fractions. In the current work, we develop new concepts
      of inverse planning which account for these two problems.

PMID- 15470921
TI  - Performance characteristics of a microMOSFET as an in vivo dosimeter in radiation
      therapy.
AB  - The commercially available microMOSFET dosimeter was characterized for its
      dosimetric properties in radiotherapy treatments. The MOSFET exhibited excellent
      correlation with the dose and was linear in the range of 5-500 cGy. No measurable
      effect in response was observed in the temperature range of 20-40 degrees C. No
      significant change in response was observed by changing the dose rate between 100
      and 600 monitor units (MU) min(-1) or change in the dose per pulse. A 3% post
      irradiation fading was observed within the first 5 h of exposure and thereafter
      it remained stable up to 60 h. A uniform energy response was observed in the
      therapy range between 4 MV and 18 MV. However, below 0.6 MeV (Cs-132), the MOSFET
      response increased with the decrease in energy. The MOSFET also had a uniform
      dose response in 6-20 MeV electron beams. The directional dependence of MOSFET
      was within +/-2% for all the energies studied. The inherent build-up of the
      MOSFET was evaluated dosimetrically and found to have varying water equivalent
      thickness, depending on the energy and the side of the beam entry. At depth, a
      single calibration factor obtained by averaging the MOSFET response over
      different field sizes, energies, orientation and depths reproduced the ion
      chamber measured dose to within 5%. The stereotactic and the penumbral
      measurements demonstrated that the MOSFET could be used in a high gradient field
      such as IMRT. The study showed that the microMOSFET dosimeter could be used as an
      in vivo dosimeter to verify the dose delivery to the patient to within +/-5%.

PMID- 15470922
TI  - Two-dimensional dosimetry in the near field of the model 200 103Pd source for
      interstitial brachytherapy implants using a thermoluminescent sheet.
AB  - A large area and highly sensitive thermoluminescent (TL) sheet film was used for
      two-dimensional dose distribution measurements at millimetre distances from a
      103Pd interstitial brachytherapy source. The TL film is made of Teflon
      homogeneously mixed with small particles of thermoluminescent material (BaSO4: Eu
      doped). This TL sheet (5 cm x 5 cm) was used to determine the relative dosimetric
      characteristics (i.e., radial dose function, 2D and 1D anisotropy functions, as
      defined by the updated AAPM Task Group No 43 report) of the model 200 103Pd
      source that emits low energy photons (21 keV). The two-dimensional dosimetry data
      were obtained for distances from the source surface to 15 mm. The radial dose
      function measured with the TL sheet is in reasonable agreement within 11% with
      the values recommended in the updated AAPM TG-43 report. All the measured 2D dose
      distributions showed limited symmetry about the source axes. The differences
      between the 1D anisotropy function values measured with the TL sheet and the data
      recommended in the updated AAPM TG-43 report were 10% at 5 mm and 7.5% at 10 mm,
      respectively, for the model 200 103Pd seed. Our experiments have demonstrated
      that it is feasible to use the TL sheet as a dosimeter in the determination of
      the dosimetric characteristics in the immediate vicinity of interstitial
      brachytherapy sources emitting low energy photons.

PMID- 15470923
TI  - Radiochromic film measurement of anisotropy function for high-dose-rate Ir-192
      brachytherapy source.
AB  - The dose distribution produced by the high-dose-rate (HDR) 192Ir source is
      inherently anisotropic due to self-absorption by the high-density source core,
      oblique filtration by the source capsule and the asymmetric geometry of the
      source capsule. To account for the dose distribution anisotropy of brachytherapy
      sources, AAPM Task Group No 43 has included a two-dimensional anisotropy
      function, F(r, theta), in the recommended dose calculation formalism. Gafchromic
      HS radiochromic film (RCF) was used to measure anisotropy function for
      microSelectron HDR 192Ir source (classic/old design). Measurements were carried
      out in a water phantom using specially fabricated PMMA cylinders at radial
      distances 1, 2, 3, 4 and 5 cm. The data so generated are comparable to both
      experimental and Monte Carlo calculated values for this source reported earlier
      by other authors. The RCF method described in this paper is comparatively high
      resolution, simple to use and is a general method, which can be applied for other
      brachytherapy sources as well.

PMID- 15470924
TI  - Commissioning of an NRC-type sealed water calorimeter at METAS using 60Co gamma
      rays.
AB  - As part of a collaborative project between the National Research Council of
      Canada (NRC) and the Swiss Federal Office of Metrology and Accreditation (METAS),
      a sealed water calorimeter was built at NRC and transferred to METAS. The
      calorimeter is operated at 4 degrees C and uses two thermistor probes in a sealed
      glass vessel containing high-purity water to measure the radiation-induced
      temperature rise. The various correction factors have been evaluated and the
      estimated standard uncertainty on the absorbed dose to water is 0.41%. An
      extensive set of measurements using 60Co gamma-rays was carried out at NRC and
      two ionization chambers were calibrated against the absorbed dose determined
      calorimetrically. The chambers were also calibrated against the NRC standard for
      absorbed dose. After transferring the calorimeter to METAS, a similar set of
      measurements was carried out using their 60Co beam and the same two ionization
      chambers were calibrated against the absorbed dose to water established at METAS.
      The discrepancy between the three sets of calibration coefficients was smaller
      than the estimated standard uncertainty of 0.47% on the ratio of any pair of
      calibration coefficients.

PMID- 15470925
TI  - High resolution MR based polymer dosimetry versus film densitometry: a systematic
      study based on the modulation transfer function approach.
AB  - Precise methods of modem radiation therapy such as intensity modulated
      radiotherapy (IMRT), brachytherapy (BT) and high LET irradiation allow for high
      dose localization in volumes of a few mm3. However, most dosimetry methods
      ionization chambers, TLD arrangements or silicon detectors, for example-are not
      capable of detecting sub-mm dose variations or do not allow for simple dose
      imaging. Magnetic resonance based polymer dosimetry (MRPD) appears to be well
      suited to three-dimensional high resolution relative dosimetry but the spatial
      resolution based on a systematic modulation transfer function (MTF) approach has
      not yet been investigated. We offer a theoretical construct for addressing the
      spatial resolution in different dose imaging systems, i.e. the dose modulation
      transfer function (DMTF) approach, an experimental realization of this concept
      with a phantom and quantitative comparisons between two dosimetric systems:
      polymer gel and film dosimetry. Polymer gel samples were irradiated by Co-60
      photons through an absorber grid which is characterized by periodic structures of
      different spatial period (a), the smallest one at width of a/2 = 280 microm. The
      modulation in dose under the grid is visualized via calibrated, high resolution,
      parameter-selective (T2) and dose images based on multi-echo MR imaging. The DMTF
      is obtained from the modulation depth of the spin-spin relaxation time (T2) after
      calibration. Voxel sizes below 0.04 mm3 could be achieved, which are
      significantly smaller than those reported in MR based dose imaging on polymer
      gels elsewhere, using a powerful gradient system and a highly sensitive small
      birdcage resonator on a whole-body 3T MR scanner. Dose modulations at 22% of
      maximum dose amplitude could be observed at about 2 line pairs per mm. The
      polymer DMTF results are compared to those of a typical clinical film-scanner
      system. This study demonstrates that MR based gel dosimetry at 200 microm pixel
      resolution might even be superior, with reference to relative spatial resolution,
      to the results of a standard film-scanner system offering a nominal scan
      resolution of 200 microm.

PMID- 15470926
TI  - Integrating a MRI scanner with a 6 MV radiotherapy accelerator: dose deposition
      in a transverse magnetic field.
AB  - Integrating magnetic resonance imaging (MRI) functionality with a radiotherapy
      accelerator can facilitate on-line, soft-tissue based, position verification. A
      technical feasibility study, in collaboration with Elekta Oncology Systems and
      Philips Medical Systems, led to the preliminary design specifications of a MRI
      accelerator. Basically the design is a 6 MV accelerator rotating around a 1.5 T
      MRI system. Several technical issues and the clinical rational are currently
      under investigation. The aim of this paper is to determine the impact of the
      transverse 1.5 T magnetic field on the dose deposition. Monte Carlo simulations
      were used to calculate the dose deposition kernel in the presence of 1.5 T. This
      kernel in turn was used to determine the dose deposition for larger fields. Also
      simulations and measurements were done in the presence of 1.1 T. The pencil beam
      dose deposition is asymmetric. For larger fields the asymmetry persists but
      decreases. For the latter the distance to dose maximum is reduced by
      approximately 5 mm, the penumbra is increased by approximately 1 mm, and the 50%
      isodose line is shifted approximately 1 mm. The dose deposition in the presence
      of 1.5 T is affected, but the effect can be taken into account in a conventional
      treatment planning procedure. The impact of the altered dose deposition for
      clinical IMRT treatments is the topic of further research.

PMID- 15470927
TI  - MRI intensity inhomogeneity correction by combining intensity and spatial
      information.
AB  - We propose a novel fully automated method for retrospective correction of
      intensity inhomogeneity, which is an undesired phenomenon in many automatic image
      analysis tasks, especially if quantitative analysis is the final goal. Besides
      most commonly used intensity features, additional spatial image features are
      incorporated to improve inhomogeneity correction and to make it more dynamic, so
      that local intensity variations can be corrected more efficiently. The proposed
      method is a four-step iterative procedure in which a non-parametric inhomogeneity
      correction is conducted. First, the probability distribution of image intensities
      and corresponding second derivatives is obtained. Second, intensity correction
      forces, condensing the probability distribution along the intensity feature, are
      computed for each voxel. Third, the inhomogeneity correction field is estimated
      by regularization of all voxel forces, and fourth, the corresponding partial
      inhomogeneity correction is performed. The degree of inhomogeneity correction
      dynamics is determined by the size of regularization kernel. The method was
      qualitatively and quantitatively evaluated on simulated and real MR brain images.
      The obtained results show that the proposed method does not corrupt inhomogeneity
      free images and successfully corrects intensity inhomogeneity artefacts even if
      these are more dynamic.

PMID- 15470928
TI  - Dose comparison between conventional and quasi-monochromatic systems for
      diagnostic radiology.
AB  - Several techniques have been introduced in the last year to reduce the dose to
      the patient by minimizing the risk of tumour induced by radiation. In this work
      the radiological potential of dose reduction in quasi-monochromatic spectra
      produced via mosaic crystal Bragg diffraction has been evaluated, and a
      comparison with conventional spectra has been performed for four standard
      examinations: head, chest, abdomen and lumbar sacral spine. We have simulated
      quasi-monochromatic x-rays with the Shadow code, and conventional spectra with
      the Spectrum Processor. By means of the PCXMC software, we have simulated four
      examinations according to parameters established by the European Guidelines, and
      calculated absorbed dose for principal organs and the effective dose. Simulations
      of quasi-monochromatic laminar beams have been performed without anti-scatter
      grid, because of their inherent scatter geometry, and compared with simulations
      with conventional beams with anti-scatter grids. Results have shown that the dose
      reduction due to the introduction of quasi-monochromatic x-rays depends on
      different parameters related to the quality of the beam, the organ composition
      and the anti-scatter grid. With parameters chosen in this study a significant
      dose reduction can be achieved for two out of four kinds of examination.

PMID- 15470929
TI  - Intrathoracic tumour motion estimation from CT imaging using the 3D optical flow
      method.
AB  - The purpose of this work was to develop and validate an automated method for
      intrathoracic tumour motion estimation from breath-hold computed tomography (BH
      CT) imaging using the three-dimensional optical flow method (3D OFM). A modified
      3D OFM algorithm provided 3D displacement vectors for each voxel which were used
      to map tumour voxels on expiration BH CT onto inspiration BH CT images. A
      thoracic phantom and simulated expiration/inspiration BH CT pairs were used for
      validation. The 3D OFM was applied to the measured inspiration and expiration BH
      CT images from one lung cancer and one oesophageal cancer patient. The resulting
      displacements were plotted in histogram format and analysed to provide insight
      regarding the tumour motion. The phantom tumour displacement was measured as 1.20
      and 2.40 cm with full-width at tenth maximum (FWTM) for the distribution of
      displacement estimates of 0.008 and 0.006 cm, respectively. The maximum error of
      any single voxel's motion estimate was 1.1 mm along the z-dimension or
      approximately one-third of the z-dimension voxel size. The simulated BH CT pairs
      revealed an rms error of less than 0.25 mm. The displacement of the oesophageal
      tumours was nonuniform and up to 1.4 cm, this was a new finding. A lung tumour
      maximum displacement of 2.4 cm was found in the case evaluated. In conclusion, 3D
      OFM provided an accurate estimation of intrathoracic tumour motion, with
      estimated errors less than the voxel dimension in a simulated motion phantom
      study. Surprisingly, oesophageal tumour motion was large and nonuniform, with
      greatest motion occurring at the gastro-oesophageal junction.

PMID- 15470930
TI  - Improved method of in vivo respiratory-gated micro-CT imaging.
AB  - The presence of motion artifacts is a typical problem in thoracic imaging.
      However, synchronizing the respiratory cycle with computed tomography (CT) image
      acquisition can reduce these artifacts. We currently employ a method of in vivo
      respiratory-gated micro-CT imaging for small laboratory animals (mice). This
      procedure involves the use of a ventilator that controls the respiratory cycle of
      the animal and provides a digital output signal that is used to trigger data
      acquisition. After inspection of the default respiratory trigger timing, we
      hypothesized that image quality could be improved by moving the data-acquisition
      window to a portion of the cycle with less respiratory motion. For this reason,
      we developed a simple delay circuit to adjust the timing of the ventilator signal
      that initiates micro-CT data acquisition. This delay circuit decreases motion
      artifacts and substantially improves image quality.

PMID- 15470931
TI  - An open-ended waveguide system for SAR system validation or probe calibration for
      frequencies above 3 GHz.
AB  - Compliance with safety guidelines prescribed in terms of maximum electromagnetic
      power absorption (specific absorption rate or SAR) for any 1- or 10-g of tissue
      is required for all newly introduced personal wireless devices such as wireless
      PCs. The prescribed SAR measuring system is a planar phantom with a relatively
      thin base of thickness 2.0 mm filled with a lossy fluid to simulate dielectric
      properties of the tissues. A well-characterized, broadband irradiator is required
      for SAR system validation or submerged E-field probe calibration for the Wi-Fi
      frequencies in the 5-6 GHz band. We describe an open-ended waveguide system that
      may be used for this purpose. Using a fourth-order polynomial least-squares fit
      to the experimental data gives SAR variations close to the bottom surface of the
      phantom that are in excellent agreement with those obtained using the finite
      difference time-domain (FDTD) numerical method. The experimentally determined
      peak 1- and 10-g SARs are within 1 to 2% of those obtained using the FDTD both at
      5.25 and 5.8 GHz.

PMID- 15470932
TI  - Monte Carlo investigations of distance-dependent effects on energy deposition in
      K-shell x-ray fluorescence bone lead measurement.
AB  - Radiation energy deposition results are presented from a Monte Carlo code
      simulating the lower part of a leg during an in vivo 109Cd K-shell x-ray
      fluorescence (KXRF) bone lead measurement. The simulations were run for a leg
      phantom model representing an adult subject, assuming concentrations of 10 microg
      Pb per gram bone mineral and tracing 500 million photons in each simulation.
      Trials were performed over a range (0.5-6.0 cm) of source-to-sample (S-S)
      distances. Energies deposited due to Compton and photoelectric processes
      occurring in the bone and the soft tissue were obtained. The data show an
      increase in the amount of energy deposited in the bone as the sample is moved
      closer to the source (from 2.0 cm to 0.5 cm). However, there is a decrease in the
      amount of energy deposited in the soft tissue as the sample is moved closer to
      the source over the same distance interval. In decreasing the S-S distance from
      2.0 cm to 0.5 cm, the amount of energy deposited in the sample as a whole was
      found to increase by 11%. By calculating the energy deposition in the bone and in
      the soft tissue as a fraction of the total energy deposited in the sample, the
      corresponding changes are quantified as a function of S-S distance. Similarly,
      the proportions of energy deposited via the photoelectric effect and Compton
      scattering are presented as a function of S-S distance.

PMID- 15470933
TI  - A generalized extension to the Hounsell-Wilkinson head scatter model.
AB  - Hounsell and Wilkinson (1997 Phys. Med. Biol. 42 1737-49) have demonstrated that
      the concept of a scatter-plane source can accurately describe head scatter in
      irregularly shaped fields produced by the MLC of an Elekta linear accelerator. In
      these linacs, the solid jaw is below the MLC set and plays no part on defining
      the view of the main source of head scatter, the flattening filter. A more
      complicated situation arises for linear accelerator head designs which
      incorporate a solid upper jaw pair with the MLC jaws further from the source.
      Application of the Hounsell and Wilkinson technique to these accelerator designs
      does not achieve the accuracy in the Elekta application. We present a generalized
      extension to Hounsell and Wilkinson's model and present results for typical
      treatment field shapes on a Siemens Primus linear accelerator.

PMID- 15470934
TI  - Matchline dosimetry in step and shoot IMRT fields: a film study.
AB  - The Varian millennium 120 multileaf collimator has curved leaf ends. Transmission
      through the leaf ends generates a small asymmetric penumbral dose effect. This
      design can lead to hot spots between neighbouring beam segments during step and
      shoot IMRT dose delivery. We have observed some matchlines with film for clinical
      beams optimized using the pinnacle radiotherapy treatment planning system; hence
      we sought to verify the optimum leaf offset required to minimize the matchline
      effect. An in-house program was created to control the MLC leaf banks in 2 cm
      steps with a 2 cm gap. The gap was varied by the following offset values from 0.0
      to 0.1 cm. Two types of radiographic films (Kodak EDR and XV films) and a
      radiochromic film (Gafchromic MD-55-2) were used to measure the optical density
      maps. The films were positioned in a solid water phantom perpendicular to the
      beam axis and irradiated at d(max) using a 6 MV photon beam. An ion chamber (IC4)
      was used to measure point doses for normalization in a beam umbral minima
      position. The relative mean peak to valley dose ratios measured with no leaf
      offset were 1.31, 1.30 and 1.31 for the XV, EDR2 and Gafchromic films,
      respectively. For a 0.07 cm gap per leaf and a performance of end leaf
      repeatability of 0.01 cm, the central matchline was reduced to about 1.0 for all
      dosimeters, with two mini-peaks measured as 1.05, 1.05 and 1.08 each side of the
      matchline, for XV, EDR2 and Gafchromic, respectively. The average relative dose
      across the umbra for this offset was XO-mat V = 1.01, EDR = 1.01 and radiochromic
      film = 1.02, respectively. While we expected the beam penumbral tails from
      segment neighbours to cause overprediction of the dose in the central valley
      regions due to the energy response of radiographic films, by normalizing all
      dosimeters to an ion chamber reading in the minimum we could not observe any
      major shape distortion between the radiographic film and radiochromic film
      results. In conclusion, relative doses measured by radiographic and radiochromic
      films agree well with IC4 within +/-2%.

PMID- 15470935
TI  - Self-concept and adolescents' refusal of unprotected sex: a test of mediating
      mechanisms among African American girls.
AB  - During adolescence, girls form self-concepts that facilitate the transition to
      adulthood. This process may entail engaging in risky sexual behaviors resulting
      in STD infection and pregnancy. This study assessed the relation between self
      concept and unwanted, unprotected sex refusal among 335 African American
      adolescent girls. The second aim was to determine whether attributes of partner
      communication about sex would act as a mediating mechanism on this hypothesized
      relationship. These assessments were made within the context of several
      theoretical models (social cognitive theory and theory of gender and power). Self
      concept was composed of self-esteem, ethnic identity, and body image, whereas
      attributes of partner communication about sex was conceptualized as frequency of
      communication, fear of condom use negotiation, and self-efficacy of condom use
      negotiation. Structural equation modeling was used to analyze data. The results
      showed that self-concept was associated with partner communication attributes
      about sex, which in turn, was associated with frequency of unprotected sex
      refusal. The hypothesized mediating role of partner communication was also
      supported. STD-HIV preventive interventions for this population may be more
      effective if they target self-concept as opposed to only self-esteem, incorporate
      an Afrocentric approach, and focus on enhancing several attributes of partner
      communication about sex.

PMID- 15470936
TI  - Adolescent predictors of young adult and adult alcohol involvement and dysphoria
      in a prospective community sample of women.
AB  - The adolescent predictors of later alcohol involvement (AI), dysphoria (D), and
      their shared association (AD) among women have not been adequately established.
      Three waves of data from an ethnically diverse community sample of women,
      assessed over 16 years are used to study how various psychosocial factors in
      adolescence influenced later drinking, depression, and their shared association.
      Structural equation models revealed that several adolescent ecodevelopmental and
      social development model variables influenced their later outcome in young
      adulthood and adulthood. The strongest relation was between adolescent Social
      Conformity and adult AD (beta = -.46) over a 16-year period, emphasizing the
      impact of this construct. Numerous other relations were revealed. For instance,
      less satisfaction with school during adolescence predicted adult AI. Having a
      good bond to the family in adolescence predicted a lower quantity of alcohol
      consumed during adulthood. Lower satisfaction with "what you want to be" during
      adolescence predicted young adult D. Higher levels of adolescent relationship
      satisfaction and school satisfaction predicted less suicidal ideation as an
      adult. Prevention interventions focusing on increasing socially conforming
      attitudes and on strengthening relationships both in and out of the home during
      adolescence are likely to be effective in reducing aspects of AI, D, and AD for
      women in the general community.

PMID- 15470937
TI  - Defining subgroups of adolescents at risk for experimental and regular smoking.
AB  - If multiple etiologies of substance use are truly at work in the population, then
      further strides in the accurate prediction of smoking and the use of other
      substances will likely be built on diverse pattern-centered approaches that
      explore the presence of multiple population subgroups across various substance
      use stages. The present study aimed to identify population subgroups defined by
      individual risk factors or risk factor constellations that prospectively predict
      specific smoking stages. Using data from the National Longitudinal Study of
      Adolescent Health (Add Health), analyses were conducted on the sample that took
      part in the baseline and 1 year follow-up assessment between 1994 and 1996.
      Classification and regression tree procedures were used to investigate the
      structure of individual risk factors, or constellations of risk, that define
      population subgroups with high rates of both experimental and established
      smoking. For each level of smoking, a relatively simple model including two
      subgroups predicted over half of the smoking cases. Findings also indicated that
      the two group models identified higher rates of regular smokers compared to
      experimental smokers. Deviant behaviors and alcohol use without permission
      independently predicted movement to experimentation at follow-up. Progression to
      regular smoking from both a nonsmoking and experimental smoking status at
      baseline were each predicted by smoking friends. Additionally, baseline levels of
      experimental use predicted movement from experimental to regular smoking, while a
      relatively low grade point average predicted rapid progression from baseline
      nonuse to regular use at follow-up. By identifying first approximations of
      patterns, these analyses may lead to clues regarding the major multiple
      mechanisms at work for the progression of smoking among adolescents.

PMID- 15470938
TI  - A conceptual framework for adaptive preventive interventions.
AB  - Recently, adaptive interventions have emerged as a new perspective on prevention
      and treatment. Adaptive interventions resemble clinical practice in that
      different dosages of certain prevention or treatment components are assigned to
      different individuals, and/or within individuals across time, with dosage varying
      in response to the intervention needs of individuals. To determine intervention
      need and thus assign dosage, adaptive interventions use prespecified decision
      rules based on each participant's values on key characteristics, called tailoring
      variables. In this paper, we offer a conceptual framework for adaptive
      interventions, discuss principles underlying the design and evaluation of such
      interventions, and review some areas where additional research is needed.

PMID- 15470939
TI  - Students' special needs and problems as reasons for the adaptation of substance
      abuse prevention curricula in the nation's middle schools.
AB  - In this study we estimate the proportion of the nation's middle school teachers
      who have adapted substance abuse curricula in response to their students' special
      problems or needs. We also explore a variety of characteristics associated with
      schools, teachers, and the curricula implemented that are associated with
      adaptations made in response to the most prevalent of these student problems or
      needs. Study data were collected in 1999 from a representative sample of lead
      substance abuse prevention teachers in the nation's public and private schools.
      We found that 79.8% of respondents report adapting their prevention curricula in
      response to at least one of the dozen student problems and needs specified. The
      problems cited most frequently, by slightly more than half of all respondents,
      relate to the needs of students who are sexually active or have discipline
      problems. Associated most strongly with adaptations for these two reasons were
      teachers who were recently trained in their curricula, and substance abuse
      prevention lessons that could readily be integrated into the school's overall
      curriculum. We discuss the need for curriculum developers to recognize the
      frequency with which, and reasons for which, teachers are adapting their
      curricula, and to include appropriate optional content that addresses students'
      needs.

PMID- 15470940
TI  - Long-term follow-up effects of a school-based drug abuse prevention program on
      adolescent risky driving.
AB  - This study examined long-term follow-up data from a large-scale randomized trial
      to determine the extent to which participation in a school-based drug abuse
      prevention program during junior high school led to less risky driving among high
      school students. Self-report data collected from students in the 7th, 10th, and
      12th grades were matched by name to students' department of motor vehicles (DMV)
      records at the end of high school. The DMV data included the total number of
      violations on students' driving records as well as the number of "points" that
      indicate the frequency and severity of the violations. A series of logistic
      regression analyses revealed that males were more likely to have violations and
      points on their driving records than females, and regular alcohol users were more
      likely to have violations and points than those who did not use alcohol
      regularly. Controlling for gender and alcohol use, students who received the drug
      prevention program during junior high school were less likely to have violations
      and points on their driving records relative to control group participants that
      did not receive the prevention program. Findings indicated that antidrinking
      attitudes mediated the effect of the intervention on driving violations, but not
      points. These results support the hypothesis that the behavioral effects of
      competence-enhancement prevention programs can extend to risk behaviors beyond
      the initial focus of intervention, such as risky driving.

PMID- 15470941
TI  - A precious resource.

PMID- 15470942
TI  - TNA's nurse-friendly designation program rolls out.

PMID- 15470943
TI  - Nurse fatigue: the human factor.

PMID- 15470944
TI  - Cultures of trauma: anthropological views of posttraumatic stress disorder in
      international health.

PMID- 15470945
TI  - The political economy of 'trauma' in Haiti in the democratic era of insecurity.
AB  - This article explores the challenges that emerge at the intersection of economies
      of compassion and terror: local, national, and international forms of
      humanitarian assistance; security practices in insecure social and institutional
      environments; questions of victimization and global reparations; and quests for
      justice, as revealed through an analysis of political violence and humanitarian
      interventions in Haiti during and after the 1991-94 coup period. Each domain is
      constrained by politics and history but can engender "occult economies" that
      challenge the intended consequences of restitution policies at international,
      national, and local levels of exchange. 'Trauma' and discourses about traumatic
      suffering are the hinge around which these economies pivot, generating new forms
      of political subjectivity for Haitian activists.

PMID- 15470946
TI  - Struggling with imaginaries of trauma and trust: the refugee experience in
      Switzerland.
AB  - This article discusses some effects of migration politics on asylum seekers and
      refugees and on the Swiss health services. It is based on multisited ethnographic
      research that tracked interpretative concepts of the refugee experience.
      Following a grounded theory approach, it identifies imaginaries of trauma and
      trust as key categories in the field of transnational migration and health. The
      psychiatric concept of trauma and a more popularized discourse of traumatic
      memory are strongly emphasized in all of the investigated field sites: the
      providers of primary health care and psychosocial services and representatives of
      social welfare agencies and law-making bodies use this "diagnosis" extensively.
      This leads refugees to develop tactics of a) identifying with the trauma
      discourse in order to become "good refugees" and achieve legal status in
      Switzerland; b) struggling with the ascribed pathologies and suffering from
      retraumatizing effects of these predominant trauma policies; and c) trying to
      refuse or subvert them by emphasizing the existence of structural violence in the
      receiving countries. An analysis of the interactions of health providers and
      refugees shows that it takes place in an environment of social and economic
      insecurity and in a shared imaginary of (mis)trust, putting at stake the moral
      economy of recent migration politics and the refugee experience.

PMID- 15470947
TI  - The work of indebtedness: the traumatic present of late capitalist Chile.
AB  - In political and biomedical discourses, "posttraumatic stress disorder" has
      become a set of organizing concepts for trauma and traumatic memory. These
      concepts, however, are predicated on an understanding of traumatic memory as a
      discrete etiological event that, when reexperienced, is productive of symptoms.
      In this essay, I explore alternative framings of trauma that arise out of
      historical changes in political economic language and from experiences of
      monetary, historical, and affective indebtedness in Santiago, Chile. This
      ethnographic research is based in an historically leftist poblacion (poor urban
      sector) and follows the interwoven narratives of a formerly exiled communist
      militant and her adopted daughter. Throughout this essay, I describe the mother's
      attempts to inhabit an untimely language of socialist politics and the daughter's
      rejection of both this language and her mother's pain. I elaborate on how these
      attempts are products of and productive of monetary and intersubjective
      indebtedness in a neoliberal present. By describing the differing historical
      languages inhabited by these subjects, I attempt to evoke an understanding of
      trauma not as an individual possession or etiological event, but rather as a
      referential dissonance in the neoliberal context. This referential dissonance
      emerges from the gap between the historical languages that inform subjectivities.
      I explore how such a gap can create contexts in which the everyday itself both
      threatens the disarticulation of the subject and produces injurious affective
      relationships. In this way, I interrogate relationships between trauma, recovery,
      and the everyday.

PMID- 15470948
TI  - Writing trauma: emotion, ethnography, and the politics of suffering among Somali
      returnees in Ethiopia.
AB  - By comparing Somali narratives of emotion and suffering with literature about
      emotion in relation to trauma and "the refugee experience," this paper
      contributes to the understanding of emotion, suffering, and trauma in different
      cultural and sociopolitical contexts, and interrogates the roles and methods of
      ethnographies of trauma in situations of high political, social, and economic
      stakes. In the mid-1990s, emotional distress among Ethiopian Somali returnees was
      about social rupture and injustice and not simply about private suffering.
      Emotion is critical to creating, recognizing, reinforcing, and mobilizing the
      moral webs on which both individual and collective survival depend. In the
      aftermath of dispossession and war, and amidst ongoing hunger and destitution,
      certain expressions of emotion carry a particularly important valence: anger,
      passion, and rhetorics of demoralization revolving around a collective narrative
      of dispossession and demands for restitution. "Experience near" descriptions of
      Somali emotion expressions cannot be conflated with "psychological" analyses or
      "Posttraumatic Stress Disorder." Somali refugee narratives index and challenge
      the embodiment in lived experience of local, national, and global institutions'
      (in)action and inequality. To the extent that academic debates over emotion and
      trauma help to shape, reinforce, or challenge the assumptions and practices of
      institutions affecting millions of lives, we researchers must address in our
      analyses the practical and political implications of how we interpret and write
      about emotion, trauma, and politics.

PMID- 15470949
TI  - Culture and pathology: flathead loneliness revisited. The 2001 Roger Allan Moore
      lecture.
AB  - My earlier considerations of Flathead loneliness and depressive disorder yielded
      an interpretation that emphasized the lack of necessary pathology in the Flathead
      experience of loneliness. In this paper I detail a shift in my thinking about the
      pathological character of loneliness, a shift traceable to a set of interactions
      that have led me away from illness experience and diagnosis to questions of
      treatment, intervention, and healing. I explore how this new set of questions
      refocused my attention-away from an exclusive preoccupation with the lonesome
      individual. I conclude with a reimagination of the pathological dimensions of
      Flathead loneliness as aspects of both group and individual health.

PMID- 15470950
TI  - The American Indian veteran and posttraumatic stress disorder: a telehealth
      assessment and formulation.

PMID- 15470951
TI  - Extraocular photoreception and circadian entrainment in nonmammalian vertebrates.
AB  - In mammals both the regulation of circadian rhythms and photoperiodic responses
      depend exclusively upon photic information provided by the lateral eyes; however,
      nonmammalian vertebrates can also rely on multiple extraocular photoreceptors to
      perform the same tasks. Extraocular photoreceptors include deep brain
      photoreceptors located in several distinct brain sites and the pineal complex,
      involving intracranial (pineal and parapineal) and extracranial (frontal organ
      and parietal eye) components. This review updates the research field of the most
      recent acquisitions concerning the roles of extraocular photoreceptors on
      circadian physiology and behavior, particularly photic entrainment and sun
      compass orientation.

PMID- 15470952
TI  - Circadian rhythm of glucose uptake in cultures of skeletal muscle cells and
      adipocytes in Wistar-Kyoto, Wistar, Goto-Kakizaki, and spontaneously hypertensive
      rats.
AB  - Hypertension and noninsulin-dependent diabetes mellitus are usually associated
      with marked glucose intolerance. Hypertensive and even nonhypertensive diabetic
      individuals display disturbances of the normal circadian blood pressure rhythm.
      However, little is known about circadian changes of the glucose uptake in muscle
      and fat cells, the major glucose utilizing tissues. Therefore, we investigated
      circadian rhythms of glucose uptake in primary muscle and fat cell cultures of
      hypertensive and type II diabetic rats and their respective control strains. 2
      Deoxy-D-(1-3H)glucose uptake was measured over 48 h after synchronization of
      cells by means of medium change with and without addition of insulin, phloretine,
      and/or staurosporine. The circadian changes of glucose uptake were assessed by
      fitting cosine curves to the uptake values. Insulin stimulation of deoxyglucose
      uptake was only present in control animals, not in hypertensive and diabetic
      rats. Deoxyglucose uptake displayed a circadian rhythm in control animals, and
      was markedly disturbed in hypertensive and diabetic animals. Blocking of glucose
      transporters by phloretine abolished the circadian pattern of deoxyglucose uptake
      indicating a role of glucose transporters in its generation. Inhibition of
      kinases by staurosporine inhibited the insulin-stimulated deoxyglucose uptake,
      but did not dampen the circadian rhythmicity of basal deoxyglucose uptake. The
      generation of the circadian rhythm of glucose uptake in muscle and fat cell
      cultures is therefore probably insulin independent and independent of protein
      kinases. In summary, our results show for the first time: (a) a circadian rhythm
      of deoxyglucose uptake in glucose utilizing muscle and fat cells in vitro, (b) a
      disruption of this rhythm in cells of hypertensive and diabetic rats.

PMID- 15470953
TI  - Multi-oscillatory control of eclosion and oviposition rhythms in Drosophila
      melanogaster: evidence from limits of entrainment studies.
AB  - The eclosion and oviposition rhythms of flies from a population of Drosophila
      melanogaster maintained under constant conditions of the laboratory were assayed
      under constant light (LL), constant darkness (DD), and light/dark (LD) cycles of
      10:10h (T20), 12:12h (T24), and 14:14h (T28). The mean (+/- 95% confidence
      interval; CI) free-running period (tau) of the oviposition rhythm was 26.34 +/-
      1.04h and 24.50 +/- 1.77h in DD and LL, respectively. The eclosion rhythm showed
      a tau of 23.33 +/- 0.63 h (mean +/- 95% CI) in DD, and eclosion was not rhythmic
      in LL. The tau of the oviposition rhythm in DD was significantly greater than
      that of the eclosion rhythm. The eclosion rhythm of all 10 replicate vials
      entrained to the three periodic light regimes, T20, T24, and T28, whereas the
      oviposition rhythm of only about 24 and 41% of the individuals entrained to T20
      and T24 regimes, respectively, while about 74% of the individuals assayed in T28
      regimes showed entrainment. Our results thus clearly indicate that the tau and
      the limits of entrainment of eclosion rhythm are different from those of the
      oviposition rhythm, and hence this reinforces the view that separate oscillators
      may regulate these two rhythms in D. melanogaster.

PMID- 15470954
TI  - Daily increments of light hours near vernal equinox synchronize circannual
      testicular cycle of tropical spotted munia.
AB  - In some long-lived organisms, particularly in tropical birds and migrants that
      spend part of the year close to the equator, endogenous circannual rhythms have
      been demonstrated in seasonal events like reproduction, molt, and migration.
      These, like the circadian rhythms, are expressed only in constant conditions of
      illumination with a periodicity deviating from 1 yr. If birds followed this
      periodicity, they would soon be out of phase with the annual calendar and perish
      and, therefore, they would need to be synchronized. However, almost nothing is
      known as to how synchronization is achieved in birds. Herein, with the help of a
      suitable model, viz., the tropical spotted munia and long-term experiments
      conducted in series over a 5-yr period, we provide direct evidence for the first
      time indicating that the segment of annual photocycle with maximal rate of
      increase prior to vernal equinox (approximately between mid-February and mid
      March) synchronizes the circannual reproductive cycle with the monsoon period of
      ample food supply through a phase delay. Data also indicate, contrary to the
      prevalent view, that birds in the tropics can perceive minor changes in day
      length, that birds respond to progressive changes in day-length as distinct from
      responding to fixed photoperiods of particular durations, and that birds can
      actually distinguish the quality of the environmental signal, viz., vernal
      equinox from early spring, or increasing days of spring from decreasing days of
      autumn. The underlying mechanisms, although yet to be identified, appear to
      involve a gonado-inhibitory rather than the conventional gonado-stimulatory
      response to increasing day-length. The photoperiodic responses of spotted munia
      are distinctly different from that of any "long-day" birds described thus far and
      do not conform to the prevalent "circadian coincidence" hypothesis of
      photoperiodism.

PMID- 15470956
TI  - Chronobiological study of the pharmacological response of rats to combination
      ketamine-midazolam.
AB  - Ketamine is commonly administered in combination with benzodiazepines to achieve
      surgical anaesthesia in rats. The aim of the present study was to analyze the
      pharmacological response of the combination ketamine-midazolam injected
      intraperitoneally at different times of day to rats. The study was conducted in
      July 2003, during the winter in the Southern hemisphere. Female prepuberal
      Sprague-Dawley rats synchronized to a 12h light:12h dark cycle (light, 07:00
      19:00h) were used as experimental animals. A combination treatment of ketamine
      (40 mg/kg) and midazolam (2 mg/kg) was administered to five different clock-time
      groups of rats (n=7/group). Duration of the latency period, ataxia, loss-of
      righting reflex (LRR), post-LRR ataxia, and total pharmacological response were
      assessed by visual assessment. Significant treatment-time differences were
      detected in the duration of LRR, post-LRR ataxia, and total pharmacological
      response duration. The longest pharmacological response occurred in rats injected
      during the light (rest) phase, and the shortest pharmacological response occurred
      in rats injected during the dark (activity) phase. Cosinor analysis documented
      circadian rhythmicity in the duration of post-LRR ataxia. The findings of the
      study indicate the duration of CNS-depression of the ketamine-midazolam
      combination exhibits treatment-time-dependent variation in the rat.

PMID- 15470955
TI  - Feeble weekly rhythmicity in hematological, cardiovascular, and thermal
      parameters in the horse.
AB  - The homeostatic control of physiological processes is affected by a variety of
      temporal programs, such as circadian rhythms, estrous cycles, and circannual
      rhythms. The existence of circaseptan rhythms (endogenous rhythms with the
      duration of a week) has been postulated but not properly verified. In this study,
      we compared plasma concentration of lactic acid, systolic and diastolic blood
      pressure, and rectal temperature in athletic horses (maintained under a weekly
      training schedule) with those in sedentary horses (maintained under a constant
      schedule throughout the week). Although exercise had robust acute effects on the
      measured parameters, measurements conducted early in the morning or in the
      evening showed significant weekly rhythmicity only in one of the parameters
      (plasma concentration of lactic acid) in a few animals. This rhythmicity was
      feeble, was present only in athletic horses, and vanished if rigorous statistical
      criteria were applied. In contrast, 24 h rhythmicity was significant in all
      parameters in all horses. We conclude that the overall 7-day pattern in
      physiological parameters of the horse is feeble and is caused by the weekly
      schedule of activity. The available evidence does not support the notion of
      endogenous, circaseptan rhythms.

PMID- 15470957
TI  - Chronotoxicity of nedaplatin in rats.
AB  - Chronotoxicologic profiles of nedaplatin, a platinum compound, were evaluated in
      rats maintained under a 12 light/12 dark cycle with light from 07:00h to 19:00 h.
      Nedaplatin (5 mg/kg) was injected intravenously, once a week for 5 weeks at
      08:00h or 20:00h. The suppression of body weight gain and reduction of creatinine
      clearance were significantly greater with the 20:00h than 08:00h treatment.
      Accumulation of nedaplatin in the renal cortex and bone marrow were also greater
      with 20:00 h treatment. There were significant relationships between the
      nedaplatin content in the kidney and bone marrow and degree of injury to each.
      These results suggest that the nedaplatin-induced toxicity depends on its dosing
      time, and it is greater with treatment at 20:00 h, during the active phase. The
      dosing-time dependency in the accumulation of nedaplatin in the tissue of the
      organs might be involved in this chronotoxicologic phenomenon.

PMID- 15470958
TI  - Circadian rhythm of irinotecan tolerability in mice.
AB  - The toxicity of irinotecan (CPT-11), a topoisomerase-I inhibitor largely used in
      cancer patients, was investigated as a function of the circadian time of its
      administration in mice, with mortality, body weight loss, leukopenia,
      neutropenia, intestinal lesions, and bone marrow cell cycle phase distribution as
      end points. Four experiments were performed on a total of 773 male mice
      standardized with 12h light/12h darkness. Irinotecan was administered daily for 4
      or 10 consecutive days (D1-4 and D1-10, respectively, in different experiments)
      at one of six circadian stages expressed in hours after light onset (HALO). The
      survival curves differed significantly as a function of the dosage and circadian
      time of drug administration by the D1-10 schedule, with 70% survival at 7 or 11
      HALO and 51% at 19 or 23 HALO (p=0.039 from log rank test). CPT-11 administration
      at 19 or 23 HALO resulted in (1) greatest mean body weight loss at nadir; (2)
      most severe colic and bone marrow lesions and/or slowest recovery; and (3)
      deepest neutropenia nadir and/or slowest hematologic recovery. These circadian
      treatment time-related differences were statistically validated. The bone marrow
      cell cycle data revealed a four to eight-fold larger G2-M phase arrest following
      irinotecan administration at 19 or 23 HALO in comparison to the other times of
      drug administration, apparently representative of the repair of more extensive
      DNA damage (p < 0.001 from ANOVA) when the medication was given at these
      circadian times. Overall, CPT-11 was better tolerated by mice treated during the
      light (animals' rest) span. The results support the administration of CPT-11 to
      cancer patients in the second half of the night, during sleep, in order to
      improve drug tolerability.

PMID- 15470959
TI  - Neuromuscular efficiency of the triceps surae in induced and voluntary
      contractions: morning and evening evaluations.
AB  - Variations in force and electromyographic (EMG) activities of skeletal muscles
      with the time-of-day have been previously described, but not for a postural
      muscle, submitted to daily postural and locomotor tasks. In this article,
      mechanical performances, EMGs, and the ratio between these parameters, i.e., the
      neuromuscular efficiency (NME), were measured on the triceps surae (TS) of eight
      subjects, two times each day, at 6:00 and 18:00 h. NME was evaluated under
      different experimental conditions (electrically induced contractions, reflex
      contractions, maximal and submaximal voluntary isometric contractions, and during
      a natural movement, a drop jump) to determine whether mechanisms, peripheral or
      central in origin, were responsible for the eventual changes in NME with time-of
      day. To calculate NME in induced conditions (NMEind), a supramaximal electrical
      stimulus was applied to the tibial nerve, and the maximal M wave of TS (TS Mmax)
      and the amplitude of the twitch tension (PtMmax) in response to this electrical
      stimulation were quantified. TS Mmax was significantly lower in the evening (mean
      gain value -10.7 +/- 5.5%, p < 0.05), whereas PtMmax was not significantly
      modified. NMEind (PtMmax/TS Mmax) was significantly higher in the evening (mean
      gain of 17.6 +/- 5.8%, p < 0.05), and this increase was necessarily peripheral in
      origin. Secondly, maximal tendon taps were applied to the Achilles tendon in
      order to quantify at the two times-of-day the reflexes in response to a
      mechanical stimulus. The maximal reflex, TS Tmax/Mmax (%), the peak amplitude of
      the twitch tension associated to this tendon jerk (PtTmax), and the corresponding
      NME (NMEreflex = PtTmax/TS Tmax/Mmax) were not affected by time-of-day,
      indicating that reflex excitability did not present daytime variations when
      tested under these conditions. Voluntary isometric contractions were required
      under maximal (MVC) and submaximal (25% MVC) conditions, and the corresponding
      torques and TS EMG were measured. MVC was higher in the evening (mean gain: 8.6
      +/- 2.7%, p < 0.05) and TS EMGmax (normalized with regard to TS Mmax) also
      increased in the evening but not significantly; thus, NMEMvc was not modified. At
      25% of MVC, TS EMG was significantly higher in the evening (mean gain of 23 +/-
      13.9%, p <0.05) and a trend for a lower NME25%MVC in the evening was observed, a
      result probably representative of a higher muscle fatigue state in the evening.
      Finally, to test the muscle capacities during a natural task, a NME index was
      calculated during a drop jump (DJ). The NMEDJ was defined as the ratio between
      jump height and mean amplitude of TS EMG (% of TS Mmax) between the drop and the
      jump. Both jump height and NMEDJ were significantly higher in the evening (mean
      gains of 10.9 +/- 4.5% and 15.7 +/- 7.4%, respectively, p <0.05). In conclusion,
      daytime changes in the efficiency of postural muscles seem to depend on both
      peripheral and central mechanisms. According to the experimental conditions, NME
      of the postural muscle could increase, remain constant, or even decrease in the
      evening, and this result may reflect reverse effects of better contractile
      capacities and higher fatigue state.

PMID- 15470960
TI  - The isolated and combined effects of menstrual cycle phase and time-of-day on
      muscle strength of eumenorrheic females.
AB  - Diurnal variation in muscle performance has been well documented in the past few
      years, but almost exclusively in the male population. The possible effects of the
      menstrual cycle on human circadian rhythms have remained equivocal, particularly
      in the context of muscle strength. The purpose of the study was to analyze the
      isolated and combined effects of circamensal variation and diurnal changes on
      muscle strength. Eight eumenorrheic females (age 30 +/- 5 yrs, height 1.63 +/-
      0.06m and body mass 66.26 +/- 4.6kg: mean +/- SD) participated in this
      investigation. Isokinetic peak torque of knee extensors and flexors of the
      dominant leg were measured at 1.05, 3.14rad.s(-1) (through 90 degrees ROM) at two
      times-of-day (06:00, 18:00 h) and five time points of the menstrual cycle
      (menses, mid-follicular, ovulation, mid-luteal, late luteal). In addition,
      maximum voluntary isometric contraction of knee extensors and flexors and
      electrically stimulated isometric contraction of the knee extensors were measured
      at 60 degrees of knee flexion. Rectal temperature was measured during 30min
      before the tests. There was a significant time-of-day effect on peak torque
      values for isometric contraction of knee extensors under electrical stimulation
      (P< 0.05). At 18:00 h, muscle force was 2.6% greater than at 06:00 h. The time-of
      day effect was not significant when the tests were performed voluntarily without
      stimulation: effect size calculations indicated small differences between morning
      and evening for maximal voluntary isometric contraction and peak torque (at
      1.05rad.s(-1) for the knee extensors. A circamensal variation was observed for
      peak torque of knee flexors at 1.05rad.s(-1), extensors at 3.14rad.s(-1), and
      also isometric contraction of knee flexors, values being greatest at the
      ovulation phase. Interaction effects between time-of-day and menstrual cycle
      phase were not observed in any of the indices of muscle strength studied. The
      phase of the menstrual cycle seemed to have a greater effect than did the time-of
      day on female muscle strength in this group of subjects. The present results
      suggest that peripheral rather than central mechanisms (e.g., motivation) are
      implicated in the diurnal variation of maximal isometric strength of women.

PMID- 15470961
TI  - Actigraphic monitoring of the activity-rest behavior of preterm and full-term
      infants at 20 months of age.
AB  - Differences in the activity-rest behavior of preterm and full-term infants
      provide an important contribution to the analysis of the ontogeny of circadian
      rhythms. In this study, we recorded the activity-rest behavior of 17 preterm and
      8 full-term infants at the approximate age of 20 months over an average of 10
      days by means of actigraphic monitoring (Actiwatch, Cambridge Neurotechnology
      Ltd.). At the same time, the parents of the infants kept a daily diary. The
      activity-rest rhythm, the nighttime sleep duration, the daytime rest duration, as
      well as the sleep quality of the infants were analyzed. Preterm and full-term
      infants at the age of 20 months show a circadian rhythm with a period length
      between 23 h 32 min (23:32 h) and 24 h 23 min (24:23 h). It can be concluded that
      the preterm and full-term infants all reached a vital developmental step by
      showing the dominant circadian rhythm in the spectrum. The daytime rest duration
      of preterm infants is significantly shorter than that of full-term infants. The
      sleep quality of preterm infants is significantly lower than that of full-term
      infants, which means that the preterm infants have a larger percentage of less
      restful nighttime sleep. In other studies preterm infants show an over
      proportional frequency of attention deficit hyperactivity disorder (ADHD). For
      this reason, future analyses should reveal whether or not actigraphic monitoring
      is a suitable means for an early identification of activity-rest behavior in
      children who may develop ADHD.

PMID- 15470962
TI  - Circadian components in energy and tension and their relation to physiological
      activation and performance.
AB  - The purpose of the study was to examine validity of R. Thayer's activation model
      regarding 24h variations of two subjective dimensions of activation (Energy and
      Tension), and their 24 h relations with indices of physiological activation and
      performance efficiency. The participants of the study (n = 28 females) spent 26 h
      under controlled laboratory conditions. Self-ratings of subjective activation and
      measurements of oral temperature, electrodermal activity, and performance on a
      visual vigilance task were done every 4 h. Twenty-four-hour variations were
      examined by means of repeated measures analyses of variance and by group mean
      cosinor analyses before and after controlling for the data trends. Self-ratings
      on both dimensions of subjective activation showed significant 24 h variation.
      Energy showed both nonrhythmic and endogenously determined circadian variation,
      while 24h variation of tension was dominantly nonrhythmic and most probably
      determined by exogenous factors. Significant 24 h covariation was found between
      energy and body temperature. A negative correlation between 24 h variation of
      energy and tension was also found. Considering low and intermediate levels of
      subjective activation established over the 24 h in this study, the association of
      the two dimensions of subjective activation did not prove to be consistent with
      the assumptions of Thayer's model.

PMID- 15470963
TI  - Olfactory discrimination and transient mood change in young men and women:
      variation by season, mood state, and time of day.
AB  - Odor performance varies by clinical state and gender, though little is known
      about its variation by season or time of day. Many odors, including lavender,
      induce transient mood changes. This study explored discrimination differences
      between various lavender oil blends and their effects on transient mood in the
      morning and evening in depressed and nondepressed adults. We also determined
      seasonal influences on these measures. A total of 169 subjects, 98 women and 71
      men (mean age +/- SD, 19.3 +/- 1.6 y) participated, with different subjects
      studied at different times of the year. The Beck Depression Inventory (BDI)
      classified subjects as depressed (score > or =10; N= 57) or nondepressed (score
      <10; N= 112). In the discrimination test, subjects compared pairs of two
      different lavender oil blends or a control. Transient change in mood was assessed
      by the Profile of Mood States (POMS) after each trial of five lavender blends
      interspersed by three control odors. Tests were conducted in the morning (08:00
      10:00 h) and evening (18:00-20:00h). In all subjects, discrimination was
      significantly better for some odor pairs than for others, thus demonstrating test
      specificity. Discrimination was better overall in the fall than winter/spring and
      better in depressed than nondepressed subjects for specific odor pairs. No
      significant gender or time-of-day differences in discriminability were detected.
      There were, however, significant group differences in transient mood profiles.
      Current depressed state affected mood response, with lavender increasing anger in
      depressed subjects only. In addition, depressed subjects and men, whether or not
      depressed, exhibited diurnal mood variation, with better mood in the evening; the
      former group also showed more evening energy. All subjects were more confused in
      the morning than evening. Season also affected transient mood; winter/spring
      tested subjects reported more vigor than fall-tested subjects. In addition,
      summer-tested subjects showed more tension in the morning, whereas fall-tested
      subjects showed the opposite pattern in the evening. In all subjects, lavender
      increased fatigue, tension, confusion, and total mood disturbance, and it
      decreased vigor. The study showed that both chronobiological (seasonal and time
      of-day) and clinical factors modify discrimination and mood response to odors.
      Brief lavender odor presentation may serve as a nonphotic method for altering
      mood in young depressed and nondepressed adults particularly during the fall, a
      time of heightened discriminability.

PMID- 15470964
TI  - Effects of alcohol on psycho-technical tests and social communication in a
      festive situation: a chronopsychological approach.
AB  - The aim of this study was to determine the effect of consuming alcoholic vs.
      nonalcoholic beverages on performance of psycho-technical tasks (attentional and
      general nonverbal intelligence tasks) and social behavior at different times of
      day. Both alcoholic and nonalcoholic consumption took place in a largely festive
      situation. The experiment was conducted on 184 degree-level and postgraduate
      students (94 female and 90 male) divided into eight independent groups for study
      at different times: 8:00 to 11:00, 11:00 to 14:00, 14:00 to 17:00, 17:00 to
      20:00h. The main result obtained, by analysis of variance (ANOVA), showed that
      time of day had no effect on the performance of psycho-technical tasks nor on
      social communication, except for the retest situation in the attentional task.
      Alcohol (equal to approximately 0.5 g/L of blood) facilitated communication, but
      basically it had no effect on any of the psycho-technical performance tests. For
      the latter, an interaction was observed between when the test was done and type
      of beverage consumed. Alcohol appears to alter the expected change in performance
      in the retest situation. The results suggest that the body's sensitivity to a
      measured quantity of alcohol differs according to the cognitive processes
      involved.

PMID- 15470965
TI  - Altered circadian relationship between serum nitric oxide, carbon dioxide, and
      uric acid in multiple sclerosis.
AB  - The free radical nitric oxide (NO*) is involved in a variety of diverse
      biological processes from acting as a vasodilator in the cardiovascular system to
      being the rate-limiting component in the production of peroxynitrite (ONOO-), a
      contributor to neurodegenerative disorders such as multiple sclerosis (MS). Uric
      acid (UA), the end product of purine metabolism in humans and a selective
      inhibitor of toxic reactions attributed to radicals formed by the interaction of
      ONOO- and CO2, is generally low in MS patients. We investigated the relationship
      between serum ONOO-, CO2, and UA in MS patients and normal controls by comparing
      the circadian characteristics of the NO* metabolites nitrite/ nitrate (NO), CO2,
      and UA. In this preliminary study, we found the functional relationship ascribed
      to the circadian timing of the peak and trough levels of NO, CO2, and UA in
      healthy subjects to be clearly altered in MS patients. These findings suggest
      that alterations in the temporal relationship between the 24h pattern in serum
      ONOO- formation and UA may either contribute to or reflect the disease processes
      in MS.

PMID- 15470966
TI  - Bright light therapy for winter depression--is phase advancing beneficial?
AB  - Bright light is the recommended treatment for winter seasonal affective disorder
      (SAD). Previously we showed that the antidepressant effect of morning (but not
      evening) light was greater than placebo after 3 weeks of treatment. Here, we
      determined if the magnitude and direction of circadian rhythm phase shifts
      produced by the bright light in the previous study were related to the
      antidepressant effects. Twenty-six SAD patients from the original sample of 96
      had their rectal temperature continuously monitored while they participated in a
      placebo-controlled parallel design conducted over six winters. After a baseline
      week, there were three treatments for 4 weeks-morning light, evening light, or
      morning placebo. Bright light was produced by light boxes (approximately 6000
      lux). Placebos were sham negative ion generators. All treatments were 1.5 h in
      duration. Depression ratings were made weekly by blind raters. Circadian phase
      shifts were determined from changes in the timing of the core body temperature
      minimum (Tmin). Morning light advanced and evening light delayed the Tmin by
      about 1 h. The placebo treatment did not alter circadian phase. As the sleep
      schedule was held constant, morning light increased and evening light decreased
      the Tmin to wake interval, or phase angle between circadian rhythms and sleep.
      Phase advance shifts and increases in the phase angle were only weakly associated
      with antidepressant response. However, there was an inverted U-shaped function
      showing that regardless of treatment assignment the greatest antidepressant
      effects occurred when the phase angle was about 3h, and that patients who moved
      closer to this phase angle benefited more than those who moved farther from it.
      However 46% of our sample had a phase angle within 30 min of this 3 h interval at
      baseline. So it does not appear that an abnormal phase angle can entirely account
      for the etiology of SAD. A majority (75%) of the responders by strict joint
      criteria had a phase angle within this range after treatment, so it appears that
      obtaining the ideal phase relationship may account for some, but not all of the
      antidepressant response. In any case, regardless of the mechanism for the
      antidepressant effect of morning light, it can be enhanced when patients sleep at
      the ideal circadian phase and reduced when they sleep at a more abnormal
      circadian phase.

PMID- 15470967
TI  - Retrospective study of the risk factors and prevalence of colic in horses after
      orthopaedic surgery.
AB  - The records of 496 orthopaedic operations on 428 horses were reviewed to estimate
      the prevalence of, and identify the risk factors for, the development of colic in
      horses after surgery. Colic was defined as any recognised sign of abdominal pain
      that could not be attributed to a concurrent disease. Fourteen of the horses
      developed colic; eight of them were undiagnosed, three were classified as
      impactions, one as tympanic colic of the colon, one as incarceration of the small
      intestine in the epiploic foramen, and one as left dorsal displacement of the
      colon in the nephrosplenic space. Morphine was associated with a four-fold
      increased risk of colic compared with the use of no opioid or butorphanol, and
      out-of-hours surgery was also associated with an increased risk.

PMID- 15470968
TI  - Use of endoscopy and renal biopsy for the diagnosis of kidney disease in free
      living birds of prey and owls.
AB  - Eighty-nine free-living birds of prey and owls were examined and blood samples
      and radiographs were taken. In addition, 126 specimens of renal tissue were
      obtained without complications, with a mean postbiopsy haemorrhage time of 67
      seconds. On average, the samples were 2.2 mm long, 1.3 mm wide and 1.0 mm deep
      and they all contained proximal and distal tubuli and from one to 89 glomeruli;
      49 of them contained from one to four intralobular veins, and on average each
      sample contained 10.7 per cent air sac tissue; 113 of the 126 samples could be
      evaluated histologically.

PMID- 15470969
TI  - T cell lymphoma in the lumbar spine of a domestic ferret (Mustela putorius furo).
AB  - A 22-month-old castrated male ferret developed acute pelvic limb paresis.
      Radiographs and computed tomography revealed a soft tissue mass with associated
      bony lysis of L5, and ultrasound-guided fine needle aspirates suggested that it
      was a lymphoma. Treatment with prednisone at immunosuppressive doses did not
      produce any detectable improvement in the ferret's clinical signs and it became
      moribund less than two weeks after they developed. A postmortem biopsy confirmed
      the presence of a lymphoma which had invaded the vertebral bone. No viruses were
      detected by cell culture, or electron microscopy.

PMID- 15470970
TI  - Choroiditis and cataracts in Atlantic salmon (Salmo salar L) recovering from
      subzero water temperatures.

PMID- 15470971
TI  - Rupture of the plantar ligament in a goat.

PMID- 15470972
TI  - Failure to isolate Escherichia coli O157 from pigs fed with bovine whey.

PMID- 15470973
TI  - Campylobacter jejuni and Arcobacter species associated with intussusception in a
      raccoon (Procyon lotor).

PMID- 15470974
TI  - Ivermectin resistance in a terminal sire sheep flock.

PMID- 15470975
TI  - Problems associated with twin pregnancies in dairy cows.

PMID- 15470976
TI  - Replacing the prolapsed bovine uterus.

PMID- 15470977
TI  - Replacing the prolapsed bovine uterus.

PMID- 15470978
TI  - Multiple offspring in roe deer.

PMID- 15470979
TI  - Bovine TB.

PMID- 15470980
TI  - Faculty clinicians and clinical scholars: mirror images in nursing.

PMID- 15470981
TI  - Nursing leadership in Australia: the Australian Peak Nursing Forum.

PMID- 15470982
TI  - Caring for a febrile child: the quality of Internet information.
AB  - AIM: A small study was conducted to evaluate the quality of information on the
      Internet about caring for a child with fever in order to alert nurses to the
      variable nature of information on the Internet for their own professional use and
      to provide advice to their patients. METHODS: Three search engines were used to
      locate web sites with information about the management of fever. A total of 22
      web sites were assessed after duplicate and irrelevant web sites were excluded
      from the analysis. Each site was evaluated against the criteria: accuracy;
      currency; source; original source; and disclosure. The web sites were also
      examined for warnings against potentially dangerous treatments. RESULTS: The
      quality of information on the Internet about the management of fever varied
      greatly, but was generally poor. Accuracy was assessed using five recommendations
      for managing fever and the proportion of web sites that included these
      recommendations ranged from 5% to 64%. Less than two-thirds of the sites recorded
      their creation or review dates. A third of the web sites did not carry warnings
      about potentially dangerous treatments. CONCLUSION: This study's findings
      highlight the poor quality of health information on the Internet and indicate
      factors to consider when using the Internet as an information source. Nurses'
      awareness of the variable quality of information on the Internet will assist them
      to identify quality information for their own professional practice and knowledge
      on which to base advice to patients.

PMID- 15470983
TI  - Expectations and perceptions of graduates' performance at the start and at the
      end of their graduate year.
AB  - This descriptive study reports on the expectations and perceptions of graduate
      performance by graduates themselves, their preceptors, and their clinical nurse
      consultants (CNCs) at the commencement of employment as a beginning level
      registered nurse, and near the end of graduates' twelve months of professional
      employment. Findings indicate that graduates expected to be functioning at a
      higher level of performance at the beginning of their graduate year than did the
      preceptors and CNCs. There was little agreement between the three groups
      regarding the rating of their expectations of graduates' nursing performance.
      When agreement between pairs of groups was examined, preceptors and CNCs agreed
      most, followed by graduates and preceptors, and graduates and CNCs. When
      perceptions of graduates' performance were compared near the end of the
      graduates' employment period, graduates rated their own nursing performance
      higher than preceptors and CNCs. Once again there was little agreement among the
      three groups. Overall, graduates and preceptors agreed most. On the basis of
      these results the question is begged, on what basis is the decision taken to
      terminate preceptorship support for graduates?

PMID- 15470984
TI  - The ennursement of old age in NSW: a history of nursing and the care of older
      people between white settlement and Federation.
AB  - The public perception of old age has come to be strongly associated with the
      nursing profession. This perception persists in Australian culture despite recent
      attempts by government and some sectors of industry to remove or dilute nursing
      from nursing homes as well as a trend by nurses themselves to not highly regard
      caring for older people. The history and heritage of the relationship between
      older people and nursing is not well known or appreciated in Australia. How and
      when did: 1) older people emerge as a social group identifiable not only by
      chronological age but also by their specific needs; and 2) nurses come to care
      for older people in Australia? The following is a brief history examining this
      unique phenomenon.

PMID- 15470985
TI  - Nursing and the health system: from the margins. Interview by Jennifer Rowe.

PMID- 15470986
TI  - Co-operation and co-morbidity: managing dual diagnosis in rural South Australia.
AB  - This paper reports a small portion of the findings from a research study that
      explored how the use of the label 'dual diagnosis' impacts on service delivery to
      people with concurrent mental health and alcohol and/or other drug problems in
      rural South Australia. Semi-structured telephone interviews were conducted with
      registered nurses from Rural Mental Health Services and Rural Drug and Alcohol
      Services. Using a form of discourse analysis we explored the interview data for
      descriptions of management of people with dual diagnosis. This paper focuses on
      the two positions of 'pulling together' and 'sharing resources' that we found in
      the data. Where the literature on management of co-morbidity usually suggests
      integrating services or expertise at the systemic level, this study shows that
      what may work best is contingent on the needs of individual clients.

PMID- 15470987
TI  - Being dialysis-dependent: a qualitative perspective.
AB  - technology of renal dialysis offers a way in which life can be sustained, so it
      is not surprising that the complex, diverse and evolving iatrogenic aspects of
      dialysis-dependency continue to be researched. However, there has been a tendency
      to take for granted the human process of making sense of the intrusiveness of
      dialysis. This study was designed to explore the meanings of dialysis-dependency.
      The study sample was 10 participants: five female, five male; five on peritoneal
      dialysis, five on haemodialysis; whose ages ranged from 22 to 68 years. Using a
      narrative methodology the following methods were used: in-depth interviews,
      narrative and thematic analysis, fieldwork/notes from five renal units,
      participant validation, and journal reflections. A thematic analysis revealed the
      continuum themes of Freedom-Restrictions, Being Normal-Being Visible, Control
      Acquiesce, Hope-Despair and Support-Abandon. The themes portrayed as continuums
      serve to remind health care professionals that those with chronic illnesses
      strive to make sense of what is happening to them. Variations within each of
      these themes can occur daily, weekly or monthly. Acceptance may never be reached
      or may be tentative. Some clients will strive for control and freedom to choose
      for themselves, others will acquiesce to the overwhelming changes wrought in
      their lives. Thus, health care professionals might consider placing the personal
      meanings of those who are dialysis-dependent to the fore, being sensitive to the
      sufferings wrought by the regime, which treats but does not cure, which sustains
      life but does not heal.

PMID- 15470989
TI  - Searching the literature: making a start.

PMID- 15470988
TI  - Ethics on the floor.
AB  - The work of the 'Human Research Ethics Committee' (HREC) is expanding as the
      dimensions of ethical practice and research grow in the clinical arena. Over the
      past five years, the demands on practitioners and ethics committee members have
      expanded, as the general public demands accountability on the part of clinical
      and other researchers. This paper presents a case study of an ethics committee in
      an Area Health Service in Sydney. It represents the views of the members as to
      why they see their job as important, what aspects are difficult, how they
      delineate between ethical/legal and scientific issues, and what are the major
      stumbling blocks for them in enacting their membership of a HREC. The data for
      the case study was collected using interviews with nine out of eleven members.
      The audio taped interviews were transcribed, the text thematically analysed for
      commonalities and contrasts, and a description of the members' perspective on
      various issues written. Issues emerging include: amount of material members read
      prior to the committee meeting, the difficulty in educating practitioners (all
      researchers) to write information sheets that are simple and comprehensible to
      laypersons, the payment of subjects for their time, the appropriate amount of
      monitoring to be applied on each project, the difficulty in letting researchers
      know that the ethics committee is committed to encouraging research and that its
      questions are intended to ensure the best possible project answering the
      researchers' questions/aims is conducted, and the slow or no response by
      researchers to ethics committee questions. The findings imply that reviewing
      research proposals for their ethical value is individual and members of human
      research ethics committees need to synthesise these in a committee context to
      make informed decisions.

PMID- 15470990
TI  - Quo vadis: Part 2.

PMID- 15470991
TI  - Resin composite restoration in primary anterior teeth using short-post technique
      and strip crowns: a case report.
AB  - A case report describing a technique for the restoration of endodontically
      treated primary maxillary incisors with resin composite short posts and celluloid
      strip crowns in a 3-year-old boy is presented. The technique offers the
      advantages of using one restorative material, improving esthetics, and reducing
      chairtime and costs.

PMID- 15470992
TI  - Safety and efficacy of a nightguard bleaching agent containing sodium fluoride
      and potassium nitrate.
AB  - OBJECTIVES: Transient sensitivity during bleaching is generally reported to
      affect 67% of patients. While most people tolerate this sensitivity, some find it
      impossible to continue treatment. The purpose of this study was to determine the
      safety and efficacy of an experimental, low-sensitivity bleaching agent. METHOD
      AND MATERIALS: Twenty-two participants bleached for a minimum of 6 hours per
      night over a 2-week period. The bleaching agent used, Experimental Product E, is
      a 10% carbamide peroxide gel containing potassium nitrate and sodium fluoride.
      Evaluations were performed at baseline and 1,2,13, and 26 weeks. Color change was
      measured using a value-ordered Vita classic shade guide and a colorimeter.
      Sensitivity of the teeth, gingiva, tongue, and/or throat was measured daily using
      a patient log. RESULTS: The median color change after 2 weeks was eight tabs.
      Approximately 36% reported sensitivity during the active whitening phase of the
      study. As a group, participants reported sensitivity during 13.7% of the total
      days spent whitening. CONCLUSION: Experimental Product E was shown to be safe.
      Participants experienced minor sensitivity during the active bleaching phase
      only. Experimental Product E was shown to be an effective bleaching agent for the
      subjects tested in this study.

PMID- 15470993
TI  - Scanning electron microscopic investigation of incidence, location, and size of
      accessory foramina in primary and permanent molars.
AB  - OBJECTIVE: The purpose of this study was to determine and compare the incidence,
      location, and size of accessory foramina in the furcation region of permanent and
      primary molars. METHOD AND MATERIALS: A random sample of 100 extracted human
      permanent maxillary and mandibular first and second molars (25 teeth of each
      type) and a random sample of 100 extracted human primary maxillary and mandibular
      molars (50 teeth of each type) were used. The crowns and roots of each tooth were
      removed at a point 1.5 mm apical to the external furcation region, and a second
      cut was made at a point 1 mm apical to the cementoenamel junction. The specimens
      were examined using scanning electron microscopy at magnifications ranging from x
      10 to x 1,250. The incidence, location, and size of accessory foramina were
      documented and statistically analyzed. RESULTS: Of the 100 permanent molars
      examined, 79% had accessory foramina with diameters ranging from 10 microm to 200
      microm. Accessory foramina were present in 94% of the primary molars, with
      diameters varying from 10 microm to 360 microm. The incidence of accessory
      foramina was significantly higher in primary than in permanent molars.
      CONCLUSION: The presence of accessory foramina with large diameters may imply
      that an inflammatory process can spread from pulpal to periodontal tissues and
      vice versa.

PMID- 15470994
TI  - New knowledge of the pathogenesis of periodontal disease.
AB  - The aim of this study was to evaluate the relationship between the accumulation
      of interleukins IL-1beta, TNF-alpha, IL-8, and chemokine RANTES (Regulated upon
      Activation Normal T-cell Expressed and Secreted) in gingival fluid and
      periodontal support tissues in patients with periodontitis. A review is also
      provided of apoptotic processes as events of major importance, highlighting the
      presence of TUNEL cells and ultrastructural morphologic changes associated with
      cell apoptosis. There appears to be further evidence to support the important
      role of inflammation control. Cytokines may be considered as markers of the
      progression and severity of periodontitis as well as indicators of an appropiate
      response to treatment. However, further studies are needed to support and
      characterize this concept.

PMID- 15470995
TI  - Prospective clinical evaluation of dental implants with sand-blasted, large-grit,
      acid-etched surfaces loaded 6 weeks after surgery.
AB  - Twenty implants with sand-blasted, large-grit, acid-etched (SLA) surfaces (ITI
      Dental System) were followed up for a period of 12 months, during which the
      following clinical criteria were evaluated: (a) absence of persistent clinical
      symptoms (pain, strange sensations, or paresthesia) after the placement of
      implants; (b) absence of recurring peri-implant inflammation or suppuration; (c)
      absence of increasing mobility, tested with Periotest; and (d) absence of bone
      loss or radiolucency around the implants. After 12 months of follow-up, all the
      loaded implants, after 6 weeks of placement, were approved under all the
      aforementioned criteria. During the analysis of the increasing mobility, tested
      with Periotest, and grouping these implants according to the site of implantation
      (mandible or maxilla), it was possible to observe that the implants presented the
      same increasing mobility.

PMID- 15470996
TI  - Aspects of oral syphilis.
AB  - The incidence of sexually transmitted diseases recently increased in the United
      States and Europe due to migration, increase in high-risk behavior, and
      abandonment of safer sex practices at the advent of anti-retroviral combination
      therapy for human immunodeficiency virus infection. This article presents four
      cases of primary oral anti perioral syphilis with differential diagnoses. It is
      important to bear this reappearing infection in mind to avoid latent infection.
      Resembling common oral infections, the primary affect disappears spontaneously,
      and the infection enters the second stage. The patient remains infected, may
      further spread the disease, and risks severe organ damage from long-standing
      infection. The antibiotic cure is inexpensive and safe and spares the patient
      mucous patches and gumma residuals, apart from severe general sequelae such as
      thoracic aorta aneurysm and neurosyphilis. However, compliance problems
      jeopardize clinical and serologic follow-up. The growing syphilis incidence
      prompts the commemoration of Dr Moriz Kaposi and his dispositive 1891 book
      Pathology and Therapy of the Syphilis. Moriz Kaposi is acknowledged as one of the
      heads of the Vienna School of Dermatology, a superb clinician, and renowned
      teacher.

PMID- 15470997
TI  - Primary syphilis of oral mucosa: case report of an unusual manifestation.
AB  - Dental clinicians and other health care providers have long been concerned about
      a variety of infectious agents that may be transmitted within the dental setting.
      Many infectious diseases, including human immunodeficiency virus, hepatitis,
      tuberculosis, and syphilis are important both because of their potential
      transmissibility and because the first manifestations of the disease may appear
      in the oral cavity. Oral disease as a consequence of primary syphilis is rare.
      This article details a patient presenting with a labial nodule as her only
      clinical manifestation of undiagnosed primary syphilis.

PMID- 15470998
TI  - Oral lichen planus.
AB  - Lichen planus is the most common dermatologic disease with oral manifestations,
      and oral lichen planus (OLP) is one of the more common mucosal conditions a
      clinician is likely to encounter in his or her practice. It is an immunologically
      based, chronic, inflammatory, mucocutaneous disorder of undetermined etiology.
      While research over the past decade has dramatically improved the overall
      understanding of the underlying pathogenesis of OLP, specific details of its
      pathogenesis and a clear understanding of why certain patients are afflicted
      while others are not, remains elusive. The care and management of patients with
      OLP continues to challenge even the most experienced clinician, and strongly
      suspected associations with chronic liver disease and oral squamous cell
      carcinoma further complicate matters. To provide prudent and competent care, oral
      health care providers must have a basic understanding of the impact the disease
      and/or its treatment may have on their patients.

PMID- 15470999
TI  - An investigation of pH changes of various cements.
AB  - OBJECTIVE: In this study, the time-related pH changes that occur in cements
      having different structures were observed. METHOD AND MATERIALS: Eight cements
      consisting of four permanent and four temporary cements were used. The materials
      were prepared according to manufacturers' instructions. The materials were used
      in 0.100 +/- 0.02-g increments, with the purpose of standardizing the effect of
      massive differences. The 80 total specimens, including 10 from each cement type,
      were prepared, and the pH value of the distilled water was measured at
      3,10,30,60, and 120 minutes, and then again 24 hours later. RESULTS: Analysis of
      variance showed the relation between the kind of cement and its pH change during
      the course of the study was statistically significant. CONCLUSION: Though
      temporary cements indicated neutral pH from the beginning of the study, the
      acidity of the other cements changed with time and took values approximate to
      neutral pH within 24 hours.

PMID- 15471000
TI  - Clinical evaluation of a resin composite and bonding agent in Class I and II
      restorations: 2-year results.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical performance and
      longevity of Tetric Ceram and Syntac Sprint restorations in stress-bearing areas
      performed in general practice. METHOD AND MATERIALS: The light-curing resin
      composite Tetric Ceram in combination with the bonding material Syntac Sprint
      were used as restorative materials in three public dental health clinics. All the
      restorations were done by general practitioners in an ordinary patient pool
      attending a public health clinic. Before starting, the general practitioners were
      instructed and trained in performing the restorations according to a standardized
      clinical procedure, and the evaluations were done according to United States
      Public Health Service criteria. One hundred forty-eight restorations (27 Class I,
      121 Class II) were done in 123 patients. After 2 years, 140 restorations (95%)
      could be assessed. Color slides and bitewings were taken to supplement the
      clinical evaluations of color match, marginal discoloration, secondary caries,
      and marginal adaptation. Wear of the restorations was evaluated according to the
      Leinfelder method. RESULTS: After 2 years, 7 out of 148 restorations had failed,
      giving a failure rate of 5% of the tested materials. Five restorations failed due
      to hypersensitivity, one to secondary caries, and one to fracture. The wear rate
      was low (mean 37 microm) and did not result in any replacement. CONCLUSION: This
      2-year study showed that clinically satisfactory results could be obtained using
      resin composite Class I and II restorations in stress-bearing areas done in
      general practice on an ordinary clientele when the clinical procedure is
      standardized.

PMID- 15471001
TI  - Risk factors for gametocyte carriage in uncomplicated falciparum malaria in
      children.
AB  - The risk factors associated with gametocytaemia at presentation and after
      treatment with different antimalarial drug regimens were evaluated in 767
      children enrolled prospectively in 5 antimalarial drug trials between July 1996
      and December 2002 in a hyperendemic area of southwestern Nigeria. The children
      were assigned to one of 6 treatment groups: chloroquine (CQ) only; pyrimethamine
      sulfadoxine (PS) only; amodiaquine (AQ) only; CQ combined with chlorpheniramine
      (CQCP); or PS combined with CQ (CQPS) or AQ (AQPS). At enrolment, 115 (15%) of
      767 children were gametocyte carriers. During follow-up, 15.6% of all patients
      (i.e. 120 patients) developed patent gametocytaemia, which in 85% (102 patients)
      had developed by day 7 following treatment. In a multiple regression model, 4
      factors were found to be independent risk factors for the presence of
      gametocytaemia at enrolment: male gender (adjusted odds ratio [AOR] = 0.55, 95%
      confidence interval [CI] 0.36-0.83, P=0.005), absence of fever (AOR = 1.61, 95%
      CI 1.05-2.5, P=0.03), duration of illness >3 days (AOR=1.57, 95% CI 1.0-2.4,
      P=0.047), and asexual parasite densities less than 5000/microl (AOR=0.42, 95% CI
      0.24-0.73, P=0.002). The presence of patent gametocytaemia at enrolment
      (AOR=0.04, 95% CI 0.02-0.07, P<0.001) and recrudescence of asexual parasites
      within 14 days were associated with the presence of gametocytaemia 7 or 14 days
      after enrolment (AOR=0.5, 95% CI 0.3-0.8, P=0.007). Delay in the time taken to
      clear the initial parasitaemia (>2 days) was associated with increased risk of
      subsequent gametocyte carriage. These findings may have implications for malaria
      control efforts in sub-Saharan Africa where control of the disease depends almost
      entirely on chemotherapy.

PMID- 15471002
TI  - Eleven years of malaria surveillance in a Sudanese village highlights unexpected
      variation in individual disease susceptibility and outbreak severity.
AB  - An analysis is presented of continuous data collected over 11 years based on
      1,902,600 person/days of observation on the malaria experience of the people of
      Daraweesh, a village in eastern Sudan. Malaria transmission is hypo-endemic: the
      acquisition of clinical immunity with age is not as obvious as in more holo
      endemic areas and malaria remained a problem in all age groups throughout the
      study. However, this population, who are of Fulani origin, showed a distinctly
      variable level of disease susceptibility. Thirty-two percent of the village never
      reported malaria symptoms or required malaria treatment while others experienced
      up to 8 clinical episodes over the 11 years of observation. Malaria incidence was
      clearly influenced by drought but much less obviously by rainfall. To what extent
      outbreak patterns are explicable in terms of anopheline factors, and to human
      immune factors, remains an interesting question for malaria modelling in this,
      and in other low transmission zones, such as the burgeoning urban areas of modern
      Africa.

PMID- 15471003
TI  - Correlation of structural development and differential expression of invasion
      related molecules in schizonts of Plasmodium falciparum.
AB  - During asexual development Plasmodium schizonts undergo a series of complex
      biochemical and structural changes. Using tightly synchronized cultures of 2 P.
      falciparum lines (clone C10 and strain ITO4) for light microscopy and
      fluorescence imaging we monitored the timing and sequence of expression of
      proteins associated with invasion-related organelles. Antibodies to rhoptry,
      micronemal and dense granule proteins (Rhoptry Associated Protein 1, Apical
      Membrane Antigen 1, Erythrocyte Binding Antigen 175, Ring-infected Erythrocyte
      Surface Antigen) and to pellicle-associated proteins (Merozoite Surface Protein
      1, PfMyosin-A) were used. Clone C10 developed faster than ITO4; this difference
      was also found in the timing of protein expression seen by immunofluorescence.
      Light microscopic data were combined with transmission electron microscopic
      analysis using serial sectioning of ITO4 schizonts to determine nuclear number
      and organellar development. Thus a timetable of schizont structural maturation
      was established. Generally, the timing of organelle-specific antigen expression
      correlates well with the ultrastructural data. Rhoptries are formed mainly
      between second and fourth nuclear divisions, micronemes between the end of the
      fourth nuclear division and merozoite separation from the residual body, while
      dense granules are generated mainly after the micronemes. PfAMA-1 appears in
      micronemes before EBA-175, suggesting micronemal heterogeneity.

PMID- 15471004
TI  - Bayesian age-stage modelling of Plasmodium falciparum sequestered parasite loads
      in severe malaria patients.
AB  - A discrete-time age-stage model is proposed for estimating the number of
      sequestered parasites in severe malaria patients. A Bayesian Markov chain Monte
      Carlo (MCMC) approach is used to model the dynamics of Plasmodium falciparum
      parasitaemia in 107 paediatric patients in a randomized controlled trial of
      quinine and artemether in Kenya, in whom 4-hourly peripheral parasitaemia
      determinations were made. The MCMC approach allows the model to be fitted
      simultaneously to the entire dataset, providing point and interval estimates for
      both population and individual patient parameters. Analysis of a simulated
      dataset indicated that the models gave good estimates of the distribution of
      parasites between different stages on enrolment, for patients with a wide range
      of initial states. The analysis of the Kenyan patients suggested that there is
      considerable variation between patients within the same centre, in both the
      proportion of sequestered parasites and the intrinsic rate of increase of the
      parasite population in the absence of treatment. The resulting models should
      prove a useful tool for cross-validating biochemical approaches for estimating
      the sequestered load.

PMID- 15471005
TI  - Potential risk factors for bovine Neospora caninum infection in Germany are not
      under the control of the farmers.
AB  - In the German state of Rhineland-Palatinate, herds were identified that were
      likely to have a Neospora caninum sero-prevalence > or = 10% by using a bulk milk
      ELISA. Individual herd data were obtained by a questionnaire. Univariate logistic
      regression showed that bulk milk positive farms had a significantly higher chance
      to report an increased abortion rate than negative farms (P(Wald)<0.1). The
      chance to have a bulk milk positive herd increased with the minimum number of
      years a farm had reported an increased abortion rate (P(Wald)<0.1). Questionnaire
      data, population and dog density as well as climatic data specific for the farm
      localization were used to identify potential risk factors for a herd to have
      acquired N. caninum infections. Within an optimized multiple logistic regression
      model 'Number of farm dogs', 'Herd size', and factors related to the municipality
      the farm was localized, i.e. 'Mean temperature in July', and 'Dog density' were
      significant risk factors (P(Wald)<0.1). The present study underlines the role
      farm dogs have in the epidemiology of neosporosis. In addition, it suggests that
      the risk a herd has to acquire N. caninum infections is also associated with
      factors related to the farm location, i.e. factors that are largely out of the
      control of farmers.

PMID- 15471006
TI  - Macrophages in the development of protective immunity against experimental Brugia
      malayi infection.
AB  - The present report compares the macrophage function in rodent hosts susceptible
      and resistant to the human lymphatic filariid Brugia malayi. Macrophages from
      both mastomys (resistant) and gerbil (susceptible) infected intraperitoneally
      (i.p.) with the infective larvae (L3) of B. malayi were isolated from peritoneal
      lavage at different time-intervals and formation rate of NO, H2O2, O2-, TNF
      alpha, glutathione peroxidase and reductase was assayed. NO release was found to
      be significantly increased in resistant mastomys as compared to gerbils and the
      release was markedly suppressed by i.p. administration of the NOS inhibitor
      aminoguanidine (AG). The AG-treated mastomys also demonstrated significantly
      greater establishment of larvae which correlated well with suppressed formation
      of NO. Nitric oxide synergizes with superoxide to form peroxynitrite radical
      (potent oxidant), which is known to be more toxic per se than NO. Results
      indicate the possible involvement of peroxynitrite in the rapid killing of larvae
      in the peritoneal cavity of mastomys. In contrast, the production of H2O2 was
      found to be enhanced in both species indicating that B. malayi L3 could withstand
      the toxic effects of H2O2. The higher level of glutathione peroxidase and
      reductase, as observed in mastomys compared with the gerbil after larval
      introduction, possibly protects the cell against the injurious effect of H2O2.
      The TNF-alpha level remained virtually unchanged in both the hosts, suggesting an
      insignificant role for this cytokine in parasite establishment.

PMID- 15471007
TI  - Characterization of Trypanosoma cruzi TcRjl locus and analysis of its transcript.
AB  - RJLs represent a recently described family of the Ras-related GTP-binding
      proteins. The Trypanosoma cruzi orthologue, TeRjl, was isolated and its locus was
      characterized in a region of almost 5 kb. Its 660 bp orf, predicting a protein of
      24.13 kDa, is present as a single copy gene in T. cruzi I lineage, and from 1-2
      copies in T. cruzi II lineage. TcRjl shares 73% aa sequence similarity with its
      closest identified orthologue, T. brucei TbRjl. RT-PCR experiments revealed that
      TcRjl is transcribed in mRNA in the 3 main life forms of the parasite, while
      Northern hybridization demonstrated that TcRjl is transcribed in T. cruzi
      epimastigotes as at least 2 transcripts, one of around 950 nt and the other of
      1500 nt. Splice-leader addition was mapped to a single site at -69 bp upstream of
      TcRjl orf indicating that the two mRNA types may derive in differences at the 3'
      of TcRjl mRNA. TcRjl locus presents considerable synteny with Rjl loci from
      Trypanosoma brucei and Leishmania major as available from their respective genome
      projects.

PMID- 15471008
TI  - Intra-specific host sharing in the manipulative parasite Acanthocephalus dirus:
      does conflict occur over host modification?
AB  - The acanthocephalan parasite Acanthocephalus dirus induces a colour change in the
      intermediate host, the aquatic isopod Caecidotea intermedius, which increases
      transmission to definitive hosts (creek chub, sunfish). We examined the potential
      for conflict to occur between infective (cystacanth) and non-infective (acanthor,
      acanthella) stages of A. dirus over the level of colour modification that should
      be induced when these stages share a host. Using a field survey, we showed that
      host sharing by infective and non-infective stages was relatively common and that
      infective and non-infective stages differed in their effects on colour
      modification. Non-infective stages induced a colour change over 40% of the body,
      whereas infective stages induced a colour change over 80%. Thus, conflict could
      occur between stages over the level of modification that should be induced. We
      then showed that mixed-stage infections induced a colour change in the host that
      was consistent with the level of modification induced by the infective stage. We
      discuss the potential significance of these results to patterns of host
      modification and their effects on stage-related survival in nature.

PMID- 15471009
TI  - Evidence for the hypothesis of strain formation in Pomphorhynchus laevis
      (Acanthocephala): an investigation using mitochondrial DNA sequences.
AB  - A hypothesis has been erected stating that in the British Isles the
      acanthocephalan, Pomphorhynchus laevis can be separated into 3 strains, an
      English, Irish and marine strain. Ecological and morphological evidence exists in
      support of this hypothesis. An investigation at the molecular level was conducted
      in order to test the validity of the existing evidence. A mitochondrial gene,
      subunit I of cytochrome c oxidase was partially sequenced from 3 Irish
      populations of P. laevis, 1 Scottish population and 3 English populations. P.
      laevis sequences from brown trout from Ireland, England and Scotland were very
      similar, showing a mean sequence divergence of 0.7%. Sequences from two
      populations of P. laevis from English chub and bullhead were also similar to each
      other (0.35% divergence). These two groups of sequences, the brown trout group
      and the chub/bullhead group were 2.2% different. These data confirm the existence
      of at least 2 strains in Ireland and Britain, although there is evidence to
      suggest that these strains are defined by their host species rather than by their
      geographical distributions.

PMID- 15471010
TI  - Long-term epidemiology, effect on body condition and interspecific interactions
      of concomitant infection by nasopharyngeal bot fly larvae (Cephenemyia auribarbis
      and Pharyngomyia picta, Oestridae) in a population of Iberian red deer (Cervus
      elaphus hispanicus).
AB  - We studied the pattern of infection and the inter-annual variation and individual
      factors affecting the infection of 2 species of nasopharyngeal bot flies,
      Cephenemyia auribarbis and Pharyngomyia picta (Diptera: Oestridae), in a
      population of Iberian red deer (Cervus elaphus hispanicus) from south central
      Spain (10 annual periods between 1990 and 2003). Mean prevalence+/-S.E.95%CI of
      infection was 35.19+/-4.24% (n=486). The frequency distribution of the parasites
      was markedly aggregated (K: 0.213, mean abundance+/-S.D.: 5.49+/-12.12). Parasite
      load of Oestridae peaked at calf and subadult age groups and declined thereafter,
      which suggests that acquired immunity may be acting. In common with other host
      parasite relationships, male hosts were found to have higher prevalence and
      abundance levels than females. The prevalence of P. picta was positively affected
      by the presence of C. auribarbis whereas the intensity of infection of P. picta
      was negatively affected by the presence of C. auribarbis. Intensity of P. picta
      in concomitant infections with C. auribarbis was lower than in pure P. picta
      infections, whilst the intensity of C. auribarbis infections did not change. This
      provides good evidence of interspecific competence, which could be dealt with by
      parasites by means of asynchronous life-cycles and different maturation periods.
      Weather also affects the dynamics and transmission rates of these parasites.
      Previous annual rainfalls positively affected the level of infection with
      oestrids. Yearly autumn rainfalls affected positively P. picta, possibly due to
      an effect on the pupal stage survival. Infection of Oestridae affected body
      condition in calves and subadults, suggesting that oestrids could have sublethal
      effects on Iberian red deer. Future research is needed to investigate the effect
      of parasites on the dynamics of the Iberian red deer.

PMID- 15471011
TI  - The relationship between IgA activity against 4th-stage larvae and density
      dependent effects on the number of 4th-stage larvae of Teladorsagia circumcincta
      in naturally infected sheep.
AB  - The number of Teladorsagia circumcincta 4th-stage larvae in naturally infected
      lambs from a single farm varied among lambs and among different years. Within
      each year the distribution of 4th-stage larvae among lambs was similar to that
      expected from a negative binomial distribution. The ratio of 4th-stage larvae to
      adult T. circumcincta was low in two years with a low mean intensity of infection
      but high in two years with a higher mean intensity of infection. The negative
      binomial distribution is defined by the mean and by k, a parameter that measures
      dispersion; k was low when mean infection intensity was low but higher when mean
      infection intensity was high. As k is an inverse index of overdispersion this
      indicated that the distribution of 4th-stage larvae was more overdispersed at low
      levels of infection. In a combined analysis, the number of adult T. circumcincta
      and the plasma IgA activity against 4th-stage larvae were both associated with
      increased numbers of 4th-stage larvae. There was a statistical interaction
      between the number of adults and IgA activity that moderated their combined
      effect.

PMID- 15471012
TI  - Characterization of excretory-secretory products from protoscoleces of
      Echinococcus granulosus and evaluation of their potential for immunodiagnosis of
      human cystic echinococcosis.
AB  - This study describes, for the first time, the characterization of excretory
      secretory antigens (ES-Ag) from Echinococcus granulosus protoscoleces, evaluating
      their usefulness in the immunodiagnosis of human cystic echinococcosis. ES-Ag
      were obtained from the first 50 h maintenance of protoscoleces in vitro. This
      preparation contained over 20 major protein components which could be
      distinguished by 1-dimensional SDS-PAGE with apparent masses between 9 and 300
      kDa. The culture of of protoscoleces from liver produced a greater variety of
      excretory-secretory protein components than those from lung. Determination of
      enzymatic activities of secreted proteins revealed the presence of phosphatases,
      lipases and glucosidases, but no proteases. These findings were compared to those
      obtained from somatic extracts of protoscoleces and hydatid cyst fluid products.
      Immunochemical characterization was performed by immunoblotting with sera from
      individuals infected by cystic echinococcosis (n = 15), non-hydatidic parasitoses
      (n = 19), various liver diseases (n = 24), lung neoplasia (n = 16), and healthy
      donors (n = 18). Antigens with apparent masses of 89, 74, 47/50, 32, and 20 kDa
      showed specificity for immunodiagnosis of human hydatidosis. The 89 and 74 kDa
      components corresponded to antigens not yet described in E. granulosus, whereas
      proteins of 41-43 kDa and 91-95 kDa were recognized by the majority of the non
      hydatid sera studied.

PMID- 15471013
TI  - Variation in the helminth community structure in spiny mice (Acomys dimidiatus)
      from four montane wadis in the St Katherine region of the Sinai Peninsula in
      Egypt.
AB  - We compared helminth communities in spiny mice (Acomys dimidiatus) from 4 wadis
      in the arid montane region of the southern Sinai in Egypt, in a 4-week period in
      late summer. Total helminth species richness was 14 (8 nematodes, 5 cestodes and
      1 acanthocephalan) with 94% of mice carrying at least 1 species and an overall
      mean species richness of 1.85. The most prevalent parasites were Protospirura
      muricola (47.8 %) and Dentostomella kuntzi (46.3%). One larval cestode,
      Joyeuxiella rossicum, represents a new host record. The helminth community was
      dominated by intestinal nematodes (88.7%) of which 58.2% were arthropod
      transmitted heteroxenic species. At the component community level, 70% of the
      worms were recovered from mice in just two wadis (Gharaba and Tlah) and 48.6 % of
      intestinal nematodes were from Wadi Gharaba. Although only 7 species of helminths
      were recorded from Wadi Gharaba, this site gave the highest Berger-Parker
      dominance index because of P. muricola. P. muricola was also dominant in Wadi El
      Arbaein whilst Syphacia minuta was the dominant species in Wadis Gebal and Tlah.
      At the infracommunity level, mean species richness and Brillouin's index of
      diversity were highest in Wadi Tlah and lowest in Wadi Gebal, and the former was
      age dependent. Whilst mice from different wadis differed in the nematodes that
      were most common, those from Wadi Gharaba carried the highest mean number of
      worms/mouse. The abundance of P. muricola in particular varied markedly between
      sites: Wadi Gharaba was distinct as the site showing the highest mean worm burden
      whereas mice from Wadi Gebal were uninfected. None of the directly transmitted
      oxyuroid nematodes showed significant variation in abundance between wadis, or
      host sex or age classes. Overall, the single extrinsic factor in the study, site
      of capture, was more important than the intrinsic factors in explaining variation
      in helminth communities in the region. We conclude that in the high mountains of
      southern Sinai, each wadi is distinct in terms of its rodent parasites, and hence
      we expect spatially different coevolutionary pressures on their hosts, with
      resultant variation in life-histories.

PMID- 15471014
TI  - Late laparoscopic reoperation of failed antireflux procedures.
AB  - Failures of antireflux procedures occur in 5% to 10% of the patients. Our
      objective is to report our experience with laparoscopic management of failed
      antireflux operations. Of 1698 patients who underwent laparoscopic treatment of
      gastroesophageal reflux disease (GERD), 53 were reoperations following either a
      previous open or laparoscopic antireflux procedure. The indications for surgical
      reoperation were persistent or recurrent GERD in 35 patients (66%), presence of
      paraesophageal hiatal hernia in 4 (7.5%), and severe dysphagia in 14 (26.4%).
      Hospital stay varied from 1 to 8 days, with an average of 1.2 days. Conversion to
      open laparotomy occurred in 10 patients (18.8%). The main causes for persistent
      or recurrent GERD were herniation (n=20) and disruption (n=12) of the
      fundoplication. Two patients had both herniation and disruption of the
      fundoplication. The main reason for severe dysphagia was tight hiatus. The most
      common reoperations were hiatal repair for hernia correction (n=26), redo
      fundoplication (n=16), and widening of the hiatus (n=12). Two patients had both
      hiatal repair and redo fundoplication. Intra (n=5) and postoperative (n=16)
      complications were frequent, but they were usually minor. There was no mortality.
      The present study demonstrated that laparoscopic reoperation for failed
      antireflux procedures may be performed safely in most patients with excellent
      result, low severe morbidity, and no mortality.

PMID- 15471015
TI  - Does the early ligation of the splenic artery reduce hemorrhage during
      laparoscopic splenectomy?
AB  - The aim of this study was to investigate whether early ligation of the splenic
      artery before splenic lysis has an effect on the amount of intraoperative
      bleeding and conversion rate during laparoscopic splenectomy. Laparoscopic
      splenectomy was performed in 34 patients with hematological diseases or splenic
      cysts between January 1993 and January 2003. The splenic artery was ligated
      before manipulation of the spleen in 22 patients (group 1) and laparoscopic
      splenectomy was performed with no previous ligation of the splenic artery in 12
      patients (group 2). Prospective data was collected and the groups compared
      regarding intraoperative blood loss, platelet count, operative time, hospital
      stay, and conversion rate. Laparoscopic splenectomy was successfully completed in
      30 (88%) patients. One patient in group 1 (5%) and 3 patients in group 2 (25%)
      required conversion due to bleeding. Estimated average blood loss was 161 mL
      (range 70-450 mL) in group 1, and 292 mL (range 100-700 mL) in group 2 (P <
      0.001). The average operative time was 140 minutes (range 80-240) in group 1, and
      155 minutes (range 80-200) in group 2 (P > 0.05). There were no statistically
      significant differences between the two groups comparing splenic size, conversion
      rate, hospital length of stay and platelet count. Early ligation of the splenic
      artery is feasible, safe and effective and may provide easy dissection and
      manipulation of the spleen during laparoscopic splenectomy with decreased
      intraoperative blood loss and no extension of the operative time.

PMID- 15471016
TI  - Laparoscopic surgical management of perforative peritonitis in enteric fever: a
      preliminary study.
AB  - Early surgery in enteric perforation is the only accepted form of treatment in
      modem day medicine and gives excellent results. Exploratory laparotomy continues
      to be the mainstay of surgical treatment and several different procedures are
      recommended in literature. Between January 1998 and November 2001, we have
      successfully managed 6 consecutive cases of enteric perforation laparoscopically
      with complete resolution of the disease. There were 4 males and 2 females in our
      study. The mean time of presentation to us was 38 hours after the perforation
      (range 22 hours to 63 hours). The mean age was 32 years (range 28 years to 43
      years). All patients presented with free air under the diaphragm. A laparoscopic
      approach was carried out through a 10 mm supraumbilical port and two 5 mm
      additional ports in the midline infraumbilical area and the left iliac fossa
      area. Simple one layer closure of the perforation was carried out with 2-0 silk
      intracorporeally and the peritoneal cavity was washed out and adequately drained.
      All perforations were localised to the terminal ileum and were single in number.
      The mean operating time was 54 minutes-(range 42 to 75 minutes). All patients
      received parenteral ofloxacin and metrogyl. Postoperative recovery was uneventful
      in all patients and there were no major complications. All patients were
      discharged from hospital by the 4th postoperative day. Follow up over a period of
      12 to 16 months revealed all patients to be in normal health. We strongly
      recommend a first line laparoscopic approach in all patients with typhoid
      perforation; as it is a safe and effective method of managing such cases.

PMID- 15471017
TI  - An optimal, cost-effective laparoscopic appendectomy technique for our surgical
      residents.
AB  - Since early 1999, we have implemented a standardized technique for laparoscopic
      appendectomy, which is simple, safe and easily learned and mastered by our
      residents. Besides superior ergonomics, it offers cosmetic advantages. It is
      inexpensive as only reusable instruments are used. It incorporates useful
      modifications, such as the use of suprapubic ports, inferior approach with
      repositioning of the videoscope from the umbilical port to the left suprapubic
      port, laparoscopic gauze swabs and instrument-assisted knotting, as well as
      skeletonization of the appendix. We analyze the outcome of this technique between
      January 2000 and December 2002. The overall conversion rate of 713 laparoscopic
      appendectomies was 8.7%, which is comparable with the "best" rates in
      international literature. Operative times (mean, 59.0 minutes) and the
      complication rate (6.7%) compared favorably with previous reports on resident
      training. In summary, our residents feel comfortable with our standardized
      approach, while producing acceptable results with low cost.

PMID- 15471018
TI  - Immediate, early, and late morbidity with laparoscopic ventral hernia repair and
      tolerance to composite mesh.
AB  - The laparoscopic repair of ventral hernias is still a controversial therapeutic
      option, and little is known of its medium- and long-term morbidity. The purpose
      of the study is to evaluate the postoperative morbidity of laparoscopic ventral
      hernia repair and analyze the clinical factors that might be related to it. 86
      consecutive patients who had ventral hernia and underwent endoscopic surgery in a
      Universitary teaching hospital. Epidemiological, clinical, postoperative
      complications, tolerance, aesthetic evaluation of the wall and recurrence rate
      are analyzed. The mean follow-up (100%) was 42 months (range: 1-5 years) and
      included clinical and ultrasonographic evaluation. The overall postoperative
      morbidity rate was 23.2%, with one case of mortality following a sepsis due to
      intestinal perforation; the rate of re-admissions and recurrences was 3.5%.
      Statistically significant relationships were shown between the complications and
      infra-umbilical location (P < 0.001), age over 60 years and female sex (P <
      0.05). The dynamic ultrasound study showed 91% and 94% of the patients to be
      adhesion-free at 1 and 3 years respectively. Aesthetic assessment of the wall at
      3 years showed persistent asymmetries in 5% of the patients and a 92% degree of
      personal satisfaction. The morbidity with laparoscopic ventral hernia repair is
      not negligible. The surgeon must know these complications and be able to treat
      them appropriately.

PMID- 15471019
TI  - Patient information following emergency laparoscopy for right iliac fossa pain.
AB  - Laparoscopy is increasingly used as a diagnostic and therapeutic tool in the
      management of emergency surgical admissions. Laparoscopic scars give little clue
      to the operation performed. Hence, the future assessment of patients re-admitted
      with abdominal pain, often needs to rely on the patient's own account of the
      operation performed. This study attempted to evaluate the quality of
      communication between surgeons and patients regarding the results of their
      laparoscopy and how much information was retained by the patients on discharge.
      Seventy-seven patients were identified from computerised medical records. A
      detailed case note review was undertaken looking at operative findings, procedure
      performed, and documentation of surgeon-to-patient communication. A questionnaire
      was posted to patients asking their opinion regarding the quality of
      communication from surgeons. The questionnaire asked specific questions regarding
      the patient's understanding of the operation performed and its findings. Overall
      communication between surgeons and patients was good. However, a small proportion
      of patients were unsure of their diagnosis and what therapeutic procedure had
      been performed following laparoscopy. This included one patient (out of 28 who
      had undergone laparoscopic appendectomy) who was unsure if their appendix had
      been removed. Two from 12 patients diagnosed with pelvic pathology at laparoscopy
      who were unclear of their diagnosis and two patients with histologically normal
      appendices who thought their appendices had been inflamed at removal. Greater
      effort must be made to inform patients of their laparoscopic findings and any
      therapeutic procedure performed. We recommend the use of written information
      leaflets to be sent to the patient's home address to ensure that all patients are
      fully aware of their laparoscopic findings. For any future emergency admission,
      the patient's knowledge of any previous surgery and whether their appendix is in
      situ is of considerable diagnostic value to the assessing clinician. More effort
      must be made to enable patients to retain such necessary information.

PMID- 15471020
TI  - An "all 5-mm ports" selective approach to laparoscopic cholecystectomy,
      appendectomy, and anti-reflux surgery.
AB  - Laparoscopic appendectomy, cholecystectomy, or anti-reflux procedures are
      conventionally performed with the use of one and often two 10/12-mm ports. While
      needlescopic or micropuncture laparoscopic procedures reduce postoperative pain,
      they invariably involve the use of one 10/12-mm port and the instruments applied
      have their ergo-dynamic shortcomings. Between September 2002 and March 2003, we
      have attempted an "all 5-mm ports" approach in 49 laparoscopic procedures, which
      included 18 of 59 laparoscopic cholecystectomies (31%), 26 diagnostic
      laparoscopies for suspected appendicitis (of which we proceeded to a laparoscopic
      appendectomy in 17 patients), and in the last 5 of 9 laparoscopic Nissen
      fundoplications. Conversion of one of the 5-mm ports to a 10-mm port was required
      in 5 of the 18 (28%) laparoscopic cholecystectomies and in 6 of the 17 (35%)
      laparoscopic appendectomies to facilitate organ retrieval in patients with large
      gallstones (>5 mm in diameter) and in obese patients with fatty mesoappendix.
      There were no conversions to open surgery. No significant differences in the
      operating time between the laparoscopic procedures performed by the all 5-mm
      ports approach or the conventional approach were observed. No intraoperative or
      postoperative complications occurred in this series. The "all 5-mm ports"
      approach to laparoscopic cholecystectomy and appendectomy in selected patients
      and to laparoscopic fundoplication appears feasible and safe. A randomised
      comparison between this approach and the conventional laparoscopic approach to
      elective cholecystectomy and fundoplication in which two of the ports employed
      are of the 10-mm diameter is warranted.

PMID- 15471021
TI  - Camera and instrument holders and their clinical value in minimally invasive
      surgery.
AB  - During minimally invasive procedures an assistant is controlling the laparoscope.
      Ideally, the surgeon should be able to manipulate all instruments including the
      camera him/herself, to avoid communication problems and disturbing camera
      movements. Camera holders return camera-control to the surgeon and stabilize the
      laparoscopic image. An additional holder can be used to stabilize an extra
      laparoscopic instrument for retracting. A literature survey has been carried out
      giving an overview of the existing "robotic" and passive camera and instrument
      holders and, if available, results of their clinical value. Benefits and
      limitations were identified. Most studies showed that camera holders, passive and
      active, provide the surgeon with a more stable image and enables them to control
      their own view direction. Only the passive holders were suitable for holding
      instruments. Comparisons between different systems are reviewed. Both active and
      passive camera and instrument holders are functional, and may be helpful to
      perform solo-surgery. The benefits of active holders are questionable in relation
      to the performance of the much simpler passive designs.

PMID- 15471022
TI  - The effect of carbon dioxide pneumoretroperitoneum on free oxygen radicals in
      rabbit retroperitoneoscopy model.
AB  - The aim of this study was to investigate the possible effects of carbon dioxide
      (CO2) pneumoretroperitoneum on free oxygen radicals in the kidney. Twelve male
      New Zealand rabbits were divided into 2 equal groups; group 1; control operation
      group (retroperitoneal space preparation without CO2 insufflation) and group 2;
      study group (10-12 mm Hg pneumoretroperitoneum for 3 hours with CO2). At the end
      of the procedure, laparotomy was performed to harvest ipsilateral and
      contralateral kidney in both groups after three hours. Kidney tissues were
      homogenized and were assayed for malondialdehyde (MDA), protein carbonyls (for
      protein oxidation), and reduced glutathione (GSH). Ipsilateral and contralateral
      kidney tissue levels of the MDA, protein carbonyls and GSH were not different in
      both the study and the control group (P > 0.05 for all comparisions).
      Corresponding ipsilateral and contralateral tissue levels of the markers, MDA and
      protein carbonyls were found to be significantly different in the study group as
      compared with the control group (P < 0.05 for the four comparisons mentioned).
      However, neither the ipsilateral nor the contralateral tissue levels of the
      marker GSH showed statistically relevant difference when the study group was
      compared with the control group. Oxidative stress was identified as a component
      of CO2 pneumoretroperitoneum-induced kidney injury using an animal model of
      retroperitoneoscopy. Oxidative stress is likely to contribute to the impairment
      of renal function after retroperitoneoscopy using a 10 mm-12 mm Hg CO2
      pneumoretroperitoneum.

PMID- 15471023
TI  - Laparoscopic treatment of intrahepatic duct stone.
AB  - Between October 1998 and November 1999, 12 patients with IHD stones, without
      severe ductal stricture, adhesion due to previous exploration, intrahepatic
      abscess or suspicious malignancy, were in the subjects of this study. A 4-port
      technique was performed, with a 4-way flexible choledochoscope, via a
      choledochotomy, for removal of the stones. The postoperative follow-up for
      recurrent stones was performed with a cholangiogram and an ultrasonogram, and the
      quality of life was evaluated by a questionnaire for the symptoms. The mean
      operating time was 288.3 (150-420) minutes. There was only one postoperative
      complication, but no intraoperative transfusions or perioperative mortality.
      Remnant stones were detected in 1 patient on the final T-tube cholangiogram,
      which was removed by percutaneous choledochoscopy, through the tract matured by
      the T-tube. There were no cholangitis or recurrent stones during the mean follow
      up period of 31.4 (10-45) months. With increasing demand for minimal
      invasiveness, the laparoscopic treatment of IHD stones could be an effective
      option.

PMID- 15471024
TI  - Laparoscopic triple cholecystectomy.
AB  - Gallbladder triplication is an unusual congenital biliary malformation, and its
      laparoscopic management has not been described. We report the 11th case of
      gallbladder triplication and the first successfully treated with laparoscopic
      cholecystectomy. We consider the procedure reliable and safe, after proper
      identification of the common biliary duct.

PMID- 15471025
TI  - Laparoscopic appendicostomy with cecoplication for antegrade colonic enema
      procedure.
AB  - Successful application of antegrade colonic enema procedure in selected patients
      with intractable constipation requires creation of an easy catheterizable but
      continent stoma. We describe a new laparoscopic technique for antegrade colonic
      enema procedure by using the in situ appendix that is combined with a Nissen-like
      cecoplication around the appendix to create a one-way valve.

PMID- 15471026
TI  - Stump appendicitis: case report and review.
AB  - The purpose of this study is to review the medical literature regarding the
      prevalence of appendicitis in patients with previous appendectomy. Stump
      appendicitis is a real entity not often considered when evaluating patients with
      right lower quadrant pain and a history of appendectomy. This leads to delays in
      diagnosis and treatment. An extensive review of the world literature using
      Medline, MD Consult, and the references of articles found using these methods to
      gather information regarding stump appendicitis. Results showed 29 cases of stump
      appendicitis have been reported in the world literature. Herein we review the
      literature as well as present a case study. Stump appendicitis is a real, yet
      probably underreported entity. It can occur after either laparoscopic or open
      appendectomy. Avoidance of a long appendiceal stump is the only suggested means
      by which to avoid its occurrence.

PMID- 15471027
TI  - Retroperitoneoscopic heminephrectomy of a horseshoe kidney for calculus disease.
AB  - Retroperitoneoscopic management of complications of a horseshoe kidney provides a
      feasible and effective alternative to conventional management. We describe a
      patient who had presented with multiple calculi and a poorly functioning left
      moiety of a horseshoe kidney, in whom we performed a retroperitoneoscopic left
      heminephrectomy. Most of the previous reports of laparoscopic nephrectomy have
      been described via the transperitoneal route. Division of the isthmus was done
      using ultrasonic shears. The patient had an uneventful recovery and was
      discharged within 24 hours.

PMID- 15471028
TI  - Laparoscopic resection of a retroperitoneal schwannoma behind the lesser omental
      sac.
AB  - Most schwannomas occur in the head, neck, or limbs with a few cases occurring in
      the retroperitoneal space. In benign schwannoma occurring in the retroperitoneal
      space, tumors are most commonly located near the adrenal gland. Herein, we report
      on a 55-year-old Japanese man with benign schwannoma (6x4 cm) behind the lesser
      omental sac, which was removed under laparoscopy. Non-functioning neurogenic
      tumor was suspected as a differential diagnosis by computed tomography,
      ultrasonography, and magnetic resonance imaging, and the patient underwent
      laparoscopic resection of the tumor. Histologically, the resected tumor was
      diagnosed as benign schwannoma. The patient was discharged from our hospital on
      the tenth postoperative day without any complications. A laparoscopic surgical
      technique is safe and feasible for the diagnosis and treatment of retroperitoneal
      benign tumors such as schwannoma.

PMID- 15471029
TI  - Pressure sore and digital neuropraxia of the thumb in laparoscopic
      cholecystectomy.

PMID- 15471030
TI  - The human lives-behind data collection in the research process.

PMID- 15471031
TI  - The new dirt on hand hygiene.
AB  - Brown et al.'s (2003) study supported that the use of alcohol-based hand rubs
      would improve hand hygiene compliance and decrease the incidence of cross
      infection. The results of this study can be used to support a group research
      utilization project that would educate nurses about the use of alcohol-based hand
      rubs as an effective technique for hand hygiene. Feasibility issues could include
      cost of the antiseptic and dispensers, placement of dispensers in relation to
      patient care, and education sessions with the nurses on how and when to use the
      antiseptic. Future research could be done to examine various nations' compliance
      with hand hygiene through use of a alcohol-based hand rubs, while also using a
      more discrete means of observation.

PMID- 15471033
TI  - A new beginning. Interview by Nick Lipley.

PMID- 15471034
TI  - Spotlight on success. Hilary Scholefield.

PMID- 15471035
TI  - A new era of health care.

PMID- 15471036
TI  - Engaging nurse executives in Agenda for Change.

PMID- 15471037
TI  - Nurses from overseas: making a world of difference.

PMID- 15471038
TI  - New leaders, new leadership: a transcultural approach.

PMID- 15471039
TI  - Managing to care? The nurse director's dilemma.

PMID- 15471040
TI  - A hard day's night.

PMID- 15471041
TI  - Strong foundations.

PMID- 15471042
TI  - Mental illness... or disability?

PMID- 15471043
TI  - Nurses and patient education.

PMID- 15471044
TI  - Practical guidelines for relief of itch.
AB  - Itch is the major symptom in, skin diseases with a variety of etiologies. Recent
      progress has been achieved in understanding the pathophysiology of itch in skin
      diseases. There are many) topical therapies availablte/for managingp ruritus.
      Emergin;g therapies include dominant ceramide moisturizers, topical
      immunomodulators, low pH moisturizers, topical aspirin, and combinations of
      moisturizers with antipruritic compounds. Using these in conjunction with
      practical measuresf or itch reduction can benefit patients in the outpatient
      clinical setting.

PMID- 15471045
TI  - Topical sensitizers in alopecia areata.
AB  - Though many therapies exist for alopecia areata, one of the most unique is
      topical sensitization. By altering the pathogenic inflammatory response with few
      side effects, sensitizers offer an attractive treatment option for many patients
      with alopecia areata, including those who have previously failed more traditional
      treatments and those who have extensive disease.

PMID- 15471046
TI  - The difficult task of delivering bad news.
AB  - Maintaining straightforward communication with the patient and family regarding
      all possibilities lays a foundation of trust and understanding between the
      patient and the health care team. In this kind of setting the patient is more
      likely to receive comfort measures and palliative care at the appropriate time in
      the process, not as a last resort or an afterthought to care.

PMID- 15471047
TI  - The ultimate advocacy role.
AB  - For nurses, end-of-life care isn't just about providing compassion. It is also
      about two very important legal documents.

PMID- 15471048
TI  - What's your assessment? Keratosis pilaris.

PMID- 15471049
TI  - Recognizing antigen: your ID please.

PMID- 15471050
TI  - 'Why won't this wound heal?' Factors affecting wound repair.

PMID- 15471051
TI  - Herpes zoster.

PMID- 15471052
TI  - Microcystic adnexal carcinoma.

PMID- 15471057
TI  - Gerontology coursework in undergraduate nursing programs in the United States.

PMID- 15471058
TI  - Nurses' attitudes toward aging and older adults--examining attitudes and
      practices among health services providers in Australia.
AB  - Data from an applied research project on ageism among health professionals were
      used to examine nurses' attitudes toward aging and working with older adults.
      Nurses were compared with groups of other health professionals, and sources of
      variation within the nurses (e.g., employer, work setting, gerontology education)
      were examined. Nurses had less accurate knowledge of aging than other health
      professionals. Nurses expressed higher anxiety about aging and were more likely
      to believe working with older adults was associated with low esteem in the
      profession. Nurses were more likely to hold positive attitudes if they worked for
      a service provider rather than an employment agency, had gerontology education,
      and worked outside the residential care sector. Improving education in
      gerontology is an important strategy in improving the attitudes of the profession
      toward older adults and could help to address nursing shortages in this sector.

PMID- 15471059
TI  - Perceived helpfulness of telephone calls--providing support for caregivers of
      family members with dementia.
AB  - The purpose of this study was to determine the perceived helpfulness of telephone
      calls to 83 caregivers of family members with dementia. Study participants were
      assigned by groups to experimental (n = 41) or attention-only control (n = 42)
      conditions. Initial baseline interview data and narrative transcripts of
      telephone calls were used in this study. Major perceived reasons for helpfulness
      were that participants were assisted in sharing thoughts and feelings, expressing
      feelings of being overwhelmed, discussing physical and psychosocial problems,
      forgetting the situation, seeking reassurance, and asking for information;
      several participants perceived the telephone calls to be lacking in helpfulness.
      Results from this study suggest family caregivers can be helped through a variety
      of social support mechanisms.

PMID- 15471060
TI  - Assaultive behavior in Alzheimer's disease: identifying immediate antecedents
      during bathing.
AB  - To identify immediate antecedents of bathing-related physical assaults against
      caregivers by nursing home residents with Alzheimer's disease and related
      disorders, videotapes of nursing home residents who physically assaulted nursing
      assistants during baths were analyzed. Caregiver behaviors that occurred
      significantly (p < .01) more often during the 5 seconds preceding an assault
      included: calling the resident by name, confrontational communication,
      invalidation of the resident's feelings, failure to prepare the resident for a
      task, disrespectful speech, any touch, absence of physical restraint, and hurried
      pace of bath. Assaults were significantly more likely when caregivers sprayed
      water without a verbal prompt; the resident's feet, axilla, or perineum were
      touched; residents exhibited signs of temperature discomfort; and multiple
      caregivers were present. Improved caregiver training and individualized, gentler
      bathing methods should be investigated as methods of reducing assaults.

PMID- 15471061
TI  - Older adults and the arts: the importance of aesthetic forms of expression in
      later life.
AB  - The purpose of this study was to examine the importance of aesthetic forms of
      expression in a randomly selected Swedish population age 65 to 89. Data were
      based on semi-structured interviews with 166 participants. Results revealed
      dance, music, literature, and pictures were important for this group of elderly
      individuals in promoting successful aging, and the connection to their everyday
      life was apparent. Participants considered viewing natural scenes and looking in
      a photo album as important aesthetic activities. The aesthetic forms of
      expression contributed to physical and intellectual activities, as well as to
      interaction with other individuals. Aesthetic experiences were related to
      feelings of timelessness and spacelessness, and served as sources of
      gratification.

PMID- 15471062
TI  - Physician orders for life-sustaining treatment form: honoring end-of-life
      directives for nursing home residents.
AB  - Physician Orders for Life-Sustaining Treatment (POLST) form provides choices
      about end-of-life care and gives these choices the power of physician orders. The
      POLST form assures end-of-life choices can be implemented in all settings, from
      the home through the health-care continuum. The use of the POLST form was
      evaluated in a pilot study in nursing homes in two eastern Washington counties.
      Chart reviews and template analysis of interviews revealed the POLST form
      accurately conveyed end-of-life wishes in 19 of 21 cases. An informed consent
      process was evidenced in 16 of 21 cases, and the POLST form was congruent with
      residents' existing advance directives for health care. The findings support the
      continued use, development, and evaluation of this promising tool for improving
      end-of-life care.

PMID- 15471063
TI  - Validation of the Reactions to Ageing Questionnaire: assessing similarities
      across several countries.
AB  - With the increasing numbers of older adults, factors impacting the effectiveness
      of provision of health care must be addressed. The literature suggests attitudes,
      particularly those of nurses, impact health service provision. This article
      reports the outcome of a multicountry validation study of the Reactions to Ageing
      Questionnaire (RAQ). The RAQ measures attitudes toward personal aging and has
      been used in Australia for 5 years. This study was designed to determine whether
      the psychometric characteristics and norms of the RAQ identified for Australian
      nurses also apply to nursing samples in Sweden and the United Kingdom. Findings
      indicate the internal structure of the RAQ extends outside Australia, with
      similar factors appearing across the three countries. Ranges and standard
      deviations indicate the instrument is able to discriminate between respondents
      within each country. Cronbach's alpha coefficients were consistent across
      countries and fell in the moderately high range. The findings indicate the RAQ
      has many potential applications in attitude assessment and in providing direction
      for training designed to address attitudinal factors that may impact the
      effectiveness of nursing practice for older adults.

PMID- 15471064
TI  - Fluoride and oral health.

PMID- 15471065
TI  - An exploratory qualitative study of Otago adolescents' views of oral health and
      oral health care.
AB  - OBJECTIVES: To investigate Otago adolescents' views of oral health and oral
      health care, in order to increase understanding of the influences on their use or
      non-use of free care. DESIGN: The study employed a qualitative approach, using
      focus groups and grounded theory analysis. PARTICIPANTS: Participants ranged in
      age from 13 to 18, and included both genders and a variety of educational
      attainments, ethnicities and family incomes. Focus groups were conducted in
      schools, training centres, a place of employment, a CYF (Child, Youth and Family)
      Home, and a University Hall of Residence. RESULTS: While aware of the normative
      pressure to attend for free dental care and engage in oral health care, Otago
      adolescents consider doing so to be "just so gay". They exhibit strongly held
      preconceptions about the expense of dentistry and the respective competence of
      dentists and dental therapists. The dental surgery environment was viewed as a
      major disincentive. Adolescent oral health beliefs centred on two models: the
      medicalised, pragmatic view of oral health (which valued the function of teeth);
      and the cosmetic view of oral health (which valued the aesthetics of teeth); or a
      combination of these two models. In both models, media advertising for oral
      health care products was a significant source of oral health information. The
      preferred oral health behaviour associated with the medicalised model was
      frequent use of chewing gum and rapid toothbrushing, and, for the cosmetic model
      frequent use of chewing gum and breath fresheners. CONCLUSIONS: These findings
      support the international literature on the use/non-use of dental services even
      when the financial barriers to seeking such services has been removed. New
      Zealand dental care has developed without reference to the changing norms of
      youth culture, and the conventional dental practice setting is not viewed by
      adolescents as being inviting or appropriate. Increasing the uptake of free oral
      health care by that group will require some innovative approaches.

PMID- 15471066
TI  - Exposed root surface: a review of aetiology, management and evidence-based
      outcomes of treatment.
AB  - Gingival recession and the associated exposure of root surfaces are a common
      finding in our patient population. Many factors have been proposed as influencing
      the development of marginal tissue recession and controversy exists over the
      concept of an "adequate" zone of attached tissue. We will explore the aetiology
      of marginal recession and the factors affecting the outcome of treatment of these
      defects through an evidence-based perspective. A review of currently accepted
      surgical techniques backed by evidence of success will be presented to
      familiarize the reader with procedures used to treat exposed root surfaces.

PMID- 15471068
TI  - Reflections on a career move.

PMID- 15471067
TI  - Oral health and dental attendance patterns of Pacific people in Christchurch, New
      Zealand.
AB  - OBJECTIVES: To determine levels of self-reported oral health, dental attendance
      patterns and barriers to seeking dental care among a Pacific community in New
      Zealand. DESIGN: Cross-sectional study using a self-completed questionnaire.
      SETTING: A Pacific Island Health Trust in Christchurch. PARTICIPANTS AND METHODS:
      Adults affiliated to the Pacific Trust Canterbury, who were in contact with any
      of the Trust's health services within a four-week period, were invited to
      complete a dental self-report questionnaire. RESULTS: One hundred and twenty-one
      Pacific adults took part in the study. The mean age of the sample was 38.7 years,
      with an age range of 17 to 77 years. Over half the respondents had not attended a
      dentist within the previous two years, and more than three-quarters had last
      attended a dentist because of pain. Most respondents had paid for their last
      treatment themselves, and over half had received an extraction because of
      infection. Participants who received a Government benefit were more likely to
      have used a public dental service than those in paid employment. Those who had
      not received education beyond secondary school were more likely to have used a
      public dental service than those who had achieved higher education levels. Males
      were more likely to have had a tooth removed due to infection than females; and
      Cook Island, Niuean and other Pacific groups were more likely to have had a tooth
      removed than Samoans. CONCLUSIONS: Most Pacific people among this sample were
      episodic dental attenders, usually presenting because of pain. Many depended on
      hospital dental departments, particularly beneficiaries, those with community
      services cards, and those in low socioeconomic occupations. Tooth loss was a
      common occurrence among this population. Further information on Pacific people's
      oral health in New Zealand would be beneficial.

PMID- 15471069
TI  - [Combination therapy with estramustine and docetaxel for hormone refractory
      prostate cancer].
AB  - Six patients with hormone refractory prostate cancer were orally administered 560
      mg of Estramustine daily in 2 equally divided doses for four or five days. In
      addition 70 mg/m2 of Docetaxel was infused through intravenous drip from day 1,
      decreasing to 40-60 mg/m2 if any side effects such as bone marrow depression were
      observed. One cycle was three weeks in hospital and one month after discharge.
      Patients were treated until progression or the development of treatment-limiting
      toxicity. In five of the six patients (83.3%), serum prostate specific antigen
      (PSA) was decreased by more than 50%. Currently, this therapy is ongoing in four
      outpatients. A side effect of leucopenia (grade 2 or 3) was observed in all
      patients. Granulocyte-colony stimulating factor (G-CSF) formulation was given as
      treatment. One case was withdrawn due to loss of appetite after one cycle. This
      therapy is considered to be effective against hormone refractory prostate cancer.
      However, further examination is needed about dosage and dosing regimen of
      Estramustine and Docetaxel.

PMID- 15471070
TI  - [Retroperitoneal fibrosarcoma with myxoid matrix: a case report].
AB  - A 54-year-old male visited a local physician with right dorsolumbar pain as the
      chief complaint. Ultrasonography revealed a tumor mass 13 cm in diameter at the
      lower part of the liver, and the patient was referred to our hospital. On
      abdominal computed tomography, uneven contrast-enhanced effects were recognized
      in the tumor. On magnetic rescmance imaging studies, T1-weighted images showed a
      hypoechoic pattern from the kidney and a weak hyperechoic pattern from the
      muscle. T2-weighted images showed uneven hyperecoic patterns. Uneven contrast
      enhanced effects were recognized inside and on the margin of the tumor. A
      diagnosis of retroperitoneal tumor was made, and surgery was performed.
      Histopathological examination revealed a fascicular alignment of spindle cells in
      the area in which the myxoid matrix is seen. On the immunological special test,
      only vimentin was positive, which led to the diagnosis of fibrosarcoma.
      Fibrosarcoma originating from retroperitoneal tumor is relatively rare.

PMID- 15471071
TI  - [A case of papillary cystadenocarcinoma of the prostate].
AB  - A 63-year-old man presented with dysuria. Ultrasonography revealed a cystic
      intravesical mass. During needle aspiration we aspirated bloody fluid. The result
      cytology was class II. We gave medication on an outpatient basis, but symptoms
      became worse. We performed transurethral resection (TUR) of prostate.
      Histopathological examination of the TUR specimen revealed a papillary
      cystadenocarcinoma of the prostate. We diagnosed the tumor as a stage B prostate
      cancer, and performed total prostatectomy. Histopathological examination of
      prostate revealed no residual cancer. Eleven cases of papillary
      cystadenocarcinoma of the prostate in the Japanese literature are reviewed
      briefly.

PMID- 15471072
TI  - [A prostatic duct carcinoma difficult to distinguish from transitional cell
      carcinoma: a case report].
AB  - A 77-year-old male with a complaint of dysuria and gross hematuria for 3 months
      visited our hospital. Abdominal ultrasonography, computed tomographic scan and
      magnetic resonance imaging revealed a prominent tumor from the bladder neck.
      Serum prostate specific antigen (PSA) level was high (1,130 ng/ml) suggesting
      prostate cancer, but transitional cell carcinoma (TCC) was detected by
      transurethral biopsy. Bone scintigraphy revealed multiple bone metastasis. Since
      gross hematuria requiring bladder tamponade continued, simple cystoprostatectomy
      and cutaneous ureterostomy were performed. Pathological findings showed prostatic
      acinar carcinoma and prostatic duct carcinoma mimicking TCC, and PSA
      immunohistochemically weak positive. The final diagnosis was prostate cancer
      consisting of acinar and ductal component. Adjuvant hormonal therapy was
      performed, but was ineffective. The patient died 2.5 months after operation. We
      reviewed and discussed 66 cases of prostatic duct carcinoma, including our case,
      in the Japanese literature.

PMID- 15471073
TI  - [New method of endocrine therapy for male infertility].
AB  - We undertook a prospective trial to compare the efficacy and adverse effects of a
      gonadotropin releasing-hormone analogue (GnRHa) and clomiphene citrate therapy
      for idiopathic normogonadotropic oligoasthenozoospermia (INOA). Fifty-nine newly
      diagnosed INOA patients were randomly allocated to treatment with GnRHa or
      clomiphene citrate. Efficacy was assessed by measuring changes in semen
      parameters prior to and after 3 months of treatment. Thirty-six INOA patients
      underwent GnRHa therapy with 15 microg of diluted buserelin acetate given once a
      day intranasally, and 23 INOA patients were treated with 50 mg of clomiphene
      citrate daily by oral administration. The mean sperm density in the GnRHa group
      increased from 13.7 x 10(6)/ml to 22.1 x 10(6)/ml (p < 0.01), while the mean
      sperm density did not change significantly in the group treated with clomiphene.
      Similarly, the mean sperm motility increased from 35.9% to 43.9% in the GnRHa
      group (p < 0.05), but did not significantly change in the clomiphene group. No
      adverse effects were observed in either group. This GnRHa treatment protocol can
      be administered on an outpatient basis and is hoped to be of benefit to INOA
      patients.

PMID- 15471074
TI  - [Treatment of traditional Chinese medicine for idiopathic male infertility].
AB  - Several Chinese herbal medicines have been used to treat patients with idiopathic
      male infertility and have been reported to improve semen quality. The clinical
      efficacy of these medicines was reviewed. The therapeutic effect of Hochu-ekki-to
      based on the pretreatment traditional diagnosis (Sho) was examined. Three months
      after the administration of Hochu-ekki-to, the semen count and motility
      significantly increased in comparison with pretreatment values. When the patients
      were classified into 3 categories based on "Sho", Hochu-ekki-to was effective in
      semen motility in patients with vacuity pattern (Kyo-Sho). Seminal plasma soluble
      Fas (sFas) levels before and three months after the administration of drug were
      analyzed. Seminal plasma sFas level elevated significantly after the
      administration of Hochu-ekki-to. After the administration of Hochu-ekki-to,
      seminal plasma sFas levels significantly correlated with sperm concentration. To
      make the best use of traditional medicine, it is important to give medication
      according to the traditional diagnosis (Sho).

PMID- 15471075
TI  - [Indication of varicocelectomy for the treatment of male infertility].
AB  - The most common and correctable known cause of male infertility is varicoceles,
      not all infertile patients with varicoceles present an improvement of fertility
      after surgical repair. In this study, we assessed preoperative factors predictive
      of improved fertility and/or semen parameters following varicocelectomy. We
      performed varicocelectomy on 148 consecutive infertile patients with varicocele
      between 1993 and 1999. Unassisted pregnancy was achieved in 38 (25.7%) patients.
      The patients with low grade varicocele, high serum follicle stimulating hormone
      (FSH), severe asthenozoospermia preoperatively had significant lower unassisted
      pregnancy rates compared to the others, respectively. Patients who have at least
      one of these three factors had a significantly lower unassisted pregnancy rate
      compared to patients without all three factors (7.7%, and 39.8%, respectively).
      In conclusion, certain preoperative variables in the physical and laboratory
      analyses appeared to predict a greater surgical response.

PMID- 15471076
TI  - [Diagnosis and treatment of obstructive azoospermia].
AB  - There are two types of azoospermia, namely, obstructive and nonobstructive
      azoospermia. Urologists play a more important role in the former, because many
      patients of the former can expect spontaneous pregnancy after surgical
      reconstruction of the seminal tract. In this review, we discuss about the causes,
      diagnosis, and treatment of obstructive azoospermia. The treatment includes
      vasovasostomy, epididymovasostomy, and transurethral resection of the ejaculatory
      duct. Surgical outcomes in our series are also described. The urologist must take
      care that the obstructive-azoospermic patients do not undergo unnecessary
      assisted reproduction procedures.

PMID- 15471077
TI  - [Male fertility in space].
AB  - The effects of simulated microgravity on mammalian reproduction were studied
      using tail-suspended mice, during parabolic flight in a jet plane and in a
      horizontal clinostat device. In the tail-suspended mouse, which is a model of the
      shift of body fluid in a microgravity environment, atrophy of the testis and
      decrease of serum testosterone level were observed. The sperm motility decreased
      in the muG condition produced by the parabolic flight. There were no
      statistically significant differences in the efficiency of achieving normal
      fertilization in vitro, but there was a statistically significant decrease in the
      number of embryos reaching the morula and blastocyst stages after 96 hours in
      culture under clinostat rotation. These results suggest that the process of
      fertilization in vitro is not sensitive to the gravitational vector. However, the
      possibility exists that microgravity increases the disturbance of spermatogenesis
      and sperm motility or the frequency of early embryonic lethality. On the
      possibility of reproduction in space, there are some problems such as the cosmic
      radiation besides gravity. It is necessary to carry out further experiments in
      outer space.

PMID- 15471078
TI  - [Optimal treatment of urolithiasis pain].
AB  - Many drugs have been used in the treatment of renal colic, but the safest and
      most effective drug has not yet been clearly defined. A questionnaire was used to
      collate the types of treatment for renal colic used by Japanese urologists. The
      main treatments were nonsteroidal analgesic (suppository) and anticholinergic
      agent. A new protocol was developed on the basis of this result, and its effect
      on renal colic was verified. The combination of an injection of a local
      anesthetic and pointillage was found to be superior to non-steroidal analgesic
      anti-inflammatory drugs and anticholinergic agent in terms of both duration of
      action and effectiveness.

PMID- 15471079
TI  - [What foods should stone formers avoid?].
AB  - Urolithiasis is a disease that has a high recurrence rate. We think that dietary
      guidance is necessary for the prevention of urolithiasis. It is important that
      stone formers eat a well-balanced diet and proper quantity of foods.

PMID- 15471080
TI  - [Study on beverages and kidney stone disease].
AB  - The incidence of upper urinary stones has been increasing since World War II in
      Japan. One of the causes is the change in dietary habit to a more westernized
      diet. The consumption of animal protein, fats and oils also correlates with the
      incidence of upper urinary stones. The results of numerous treatments for
      preventing formation of calcium stones are not sufficient, and the improvement of
      daily life habits and dietary advice have been proposed to be important. An
      increased intake of fluid is of great value for patients with stone diseases,
      irrespective of the stone composition. We discuss whether or not non-alcoholic
      and alcoholic beverages, are appropriate for prevention of stone diseases from
      the viewpoint of the contents of the beverages.

PMID- 15471081
TI  - [Surgical treatmnt for urolithiasis (in view of medical economics)].
AB  - Surgical treatment for upper urinary stones has dramatically changed since
      extracorporeal shock wave lithotripsy (ESWL) was introduced in 1985 in Japan.
      Since then, the number of ESWL apparatus is increasing year by year, and there
      were about 800 ESWL apparatus available in Japan in 2001. On the other hand, the
      number of patients with upper urinary stones are also increasing in Japan, and
      the age-adjusted annual incidence of first-episode upper urinary tract stones in
      1995 was estimated at 68.9 per 100,000 (100.1 in men and 55.4 in women), a steady
      increase from 54.2 in 1965. Under these circumstances, it would be very important
      to treat stone patients surgically even from an economical point of view, because
      the cost of ESWL is very expensive and more than 90% of the patients with
      urolithiasis are now treated by ESWL. In this paper, the medical economics of
      urolithiasis in Japan is discussed especially in the surgical treatment.

PMID- 15471082
TI  - [Economical aspects on the treatments of urolithiasis by surgical methods:
      comparison of surgical method selections and world status].
AB  - Economical elements including surgical fee and hosipital stay become larger in
      the selection of surgical methods for the treatment of urinary stones. Then,
      urologists need to explain to patients the treatment cost to obtain informed
      consent. By comparing the data from participants' answer to Debate 1 at the 82th
      annual meeting of the Japanese Urological Association (April 2002, Tokyo) and
      questionnaire responses from the members of the annual meeting of central
      division of Japanese Urological Association (November 2002, Nagoya), we surveyed
      the trends of surgical methods on the treatments of staghorn caliculi and lower
      ureter stones. Furthermore, we clarified the cost of these methods. Based on the
      status of world countries, we demonstrate the ideal selection including
      economical aspects on the selection of endourological method.

PMID- 15471083
TI  - [Future perspective on the prevention of nephrolithiasis].
AB  - Renal stone formation has been explained by the physicochemical theory; i.e.,
      nucleation, growth and aggregation of crystals in the urine. Current medical
      prevention is based on this theory and seeks to modulate promoters and inhibitors
      of stone formation. Recent studies have identified increasing numbers of
      macromolecular inhibitors such as glycosaminoglycans, bikunin, osteopontin and
      urinary prothrombin F1. These appear to be more important than low-molecular
      inhibitors like citrate. On the other hand, many investigators have focused on
      the role of tubular epithelial cells in stone formation. While crystal retention
      in the nephron has been considered necessary for stone formation, we and others
      have found that calcium oxalate crystals can bind to renal epithelial cells.
      Moreover, available evidence suggests that oxalate and/or calcium oxalate
      crystals can damage renal epithelial cells and enhance crystal binding.
      Concurrently, oxalate exposure induces genes coding macromolecular inhibitors,
      which are supposed to be a protective mechanism against stone formation. Thus,
      understanding of the mechanisms involved in kidney stone formation could lead to
      new therapeutic approaches to preventing stone recurrence. However, clinical
      application of the prophylactic approaches proposed here awaits further progress
      in basic research using rapidly growing new technologies. Application of the DNA
      microarray technique to the rat stone model may provide a clue to understanding
      stone forming process at the genetic level. In addition, case-control association
      analysis using single nucleotide polymorphism as a marker may be useful for
      detecting susceptibility genes in patients with calcium stone disease.

PMID- 15471084
TI  - [Behavioral situation at onset of paradoxical brain embolism due to patent
      foramen ovale].
AB  - The goal of this study was to determine whether there was difference in
      behavioral situation at onset of stroke between the patients with right-to-left
      shunt whose stroke was diagnosed as paradoxical brain embolism according to the
      new criteria proposed by Strategies against Stroke Study for Young Adults in
      Japan (SASSY-Japan) and whose stroke was not. Among 365 consecutive patients with
      possible acute ischemic stroke who underwent transesophageal echocardiography, we
      compared clinical profiles of the following three patient groups: patients with
      patent foramen ovale whose stroke was diagnosed as paradoxical brain embolism
      (group A), patients with patent foramen ovale whose stroke was not diagnosed as
      paradoxical brain embolism (group B), and patients without patent foramen ovale
      whose stroke was diagnosed as cardiogenic brain embolism (group C). Patent
      foramen ovale was present on echocardiogram in 76 of 365 patients (21%). Among
      them, 19 patients were classified into group A and 34 into group B. Group C was
      composed of 69 patients. At stroke onset, 3 patients in group A took behavior
      with positive Valsalva maneuver, 2 in group B, and 1 in group C. Similarly at
      stroke onset, 4 patients in group A just stood up from long-time sitting
      position, 1 in group B, and 1 in group C. In all, stroke onset following Valsalva
      maneuver or long-time sitting position was positive in 37% of group A, 9% of
      group B, and 3% of group C, and was most frequent in group A (p < 0.0001). In
      group A, the frequency of Valsalva maneuver or long-time sitting position at
      stroke onset was higher than the frequency of detection of venous thrombus (21%).
      The result indicates that Valsalva maneuver and long-time sitting position
      contribute to occurrence of paradoxical brain embolism. We think that these
      behavioral situations are appropriate diagnostic criteria for paradoxical brain
      embolism.

PMID- 15471085
TI  - [Clinical features of neuropathies in a group of patients associated with anti
      GalNAc-GD1a antibody].
AB  - To clarify the clinical features of patients with anti-GalNAc-GD1a antibody, we
      retrospectively investigated which conditions were associated with anti-GalNAc
      GD1a antibody in a large number of patients. Sixty-four out of 1,713 patients had
      anti-GalNAc-GD1a IgG antibody. Fifty-seven (89%) were diagnosed with Guillain
      Barre syndrome (GBS) or atypical GBS with preserved deep tendon reflexes. These
      patients were characterized by young man, antecedent diarrhea, distal-dominant
      limb weakness, and absence of cranial nerve impairment and sensory disturbance.
      Some of sera from patients had anti-GM1, anti-GM1b, and anti-GD1a IgG antibodies
      associated with axonal GBS. Our study suggests that the anti-GalNAc-GD1a antibody
      testing is useful for supporting the diagnosis of GBS. In addition, fine
      specificity of the antibody also was clarified.

PMID- 15471086
TI  - [A neuro-ophthalmological analysis in 80 cases of multiple sclerosis].
AB  - We report clinical features of ocular symptoms in 80 patients with multiple
      sclerosis (MS). Serial 80 patients with MS had been admitted to our Neurology
      Ward at Nihon University Itabashi Hospital from April 1980 to October 2003. All
      patients were also examined by our neuro-ophthalmologists. Ocular symptoms were
      observed in 49 patients, and 14 patients were male and 35 were female. Patients'
      age at onset varied from 17 to 51 years old, with the average being 31.2 +/- 4.2
      years. Observation period were 6 months to15 years, and average 5.4 +/- 1.4
      years. In visual symptoms, retrobulbar optic neuritis was observed in 33 eyes of
      26 patients. On the first attack of retrobulbar optic neuritis, 25 eyes showed a
      corrected visual acuity of less than 0.1. After corticosteroid therapy, a
      corrected visual acuity improved more than 1.0 in 17 eyes. Optic atrophy was
      observed in 22 eyes and color blindness in 16 eyes. On the second attack of
      retrobulbar optic neuritis on the same eyes, 6 of 9 eyes showed a corrected
      visual acuity of less than 0.1 after corticosteroid therapy. Optic atrophy and
      color blindness were confirmed in all eyes. Homonymous hemianopia was detected in
      2 female patients and completely resolved after corticosteroid therapy. On the
      other hand, ocular motor symptoms were observed in 29 patients. Internuclear
      ophthalmoplegia was detected in 18 patients, nystagmus in 5, abducens nerve palsy
      in 5, skew deviation in 5, one-and-a-half syndrome in 2, gaze palsy in 2 and
      ocular myoclonus in 1. In all except one patient with primary position downbeat
      nystagmus, ocular myoclonus and bilateral internuclear ophthalmoplegia, these
      symptoms improved completely within 8 weeks after corticosteroid therapy. We
      emphasize that cooperation of neurologist and ophthalmologist plays an important
      role for clinical evaluation of MS patients.

PMID- 15471087
TI  - [Multiple brain infarctions in a young patient with Buerger's disease. A case
      report of cerebral thromboangiitis obliterans].
AB  - We report a 46-year-old woman with Buerger's disease who presented vascular
      dementia. In her early thirties, she began to feel cold sensation and pain in the
      lower extremities and later developed Raynaud's phenomenon in the upper
      extremities. The diagnosis of Buerger's disease was established on the basis of
      angiographic findings which showed the obstruction of peripheral vessels in both
      anterior tibial arteries. She was admitted to our hospital because of a transient
      attack of left brachial monoparesis and two episodes of epileptic seizure with
      progressive cognitive impairment for preceding five years. Neurological
      examination revealed acalculia, constructional apraxia, recent memory
      disturbance, and hyperreflexia of the left limbs without motor disturbance. Brain
      MRI revealed multiple infarctions mainly located in the border zone territories
      of the major cerebral arteries. Conventional angiography failed to detect
      abnormalities of cerebral vessels. She had no cardiovascular abnormality or
      coagulopathy. Cerebrovascular complications, so-called cerebral thoromboangiitis
      obliterans (CTAO), occur approximately in 2% of patients with Buerger's disease.
      CTAO has two types. Type 1 is associated with large artery changes and type 2 is
      associated with medium and small artery changes. Patients with type 2 CTAO
      usually have multiple infarcts in the cerebral arterial border zones and may
      develop progressive cognitive decline without motor deficit. Her clinical
      features are compatible with type 2 CTAO. While CTAO is a relatively rare
      manifestation of Buerger's disease, it should be suspected in cases of Buerger's
      disease in association with cognitive impairment of unknown onset.

PMID- 15471088
TI  - [A case of hypertrophic pachymeningitis, resolved by antimicrobial therapy].
AB  - A 65-year-old woman with diabetes mellitus and chronic otitis media developed
      headache, fever, and hoarseness, all of which did not responded to the oral
      antibiotics. As stiff neck and lower cranial nerve palsies appeared, bacterial
      meningitis was suspected. Neurological examination revealed the right hearing
      disturbance, right recurrent laryngeal nerve palsy, left sternocleidomastoid
      muscle atrophy and bilateral tongue atrophy. The CSF examination revealed mild
      pleocytosis and elevated protein, but no bacterial organism was cultured from the
      CSF. CT scans showed bilateral mastoiditis, and the right mastoid process and a
      posterior part of the petrous bone were eroded, indicating the exposed bony
      structures to the posterior fossa. MRI scans demonstrated the thickening of the
      dura mater of the posterior fossa and the right cerebellar tentorium. This is a
      rare example of bacterial pachymeningitis of the posterior fossa, the clinical
      symptoms and MRI findings of which resolved solely by antimicrobial agents
      without corticosteroid.

PMID- 15471089
TI  - [Neuroradiological study of progressive multifocal leukoencephalopathy associated
      with acquired immunodeficiency syndrome by MR imaging including diffusion
      weighted imaging].
AB  - A 27-year-old man presented with subacute progressive left hemiparesis and hemi
      sensory loss. Laboratory examinations revealed CD4 count at 14/microl, the HIV
      antibody positive, and HIV-RNA at 4.3 x 10(4) copies. Brain CT showed hypodence
      areas without contrast enhancement or mass effect in the right parietooccipital
      white matter and the right external capsule. On MR imaging, the lesion in the
      parietooccipital area showed hypointensity without enhancement on T1-weighted
      images and hyperintensity on T2-weighted images. On FLAIR images, the lesion
      showed hypointensity surrounded by hyperintensity. Meanwhile, diffusion-weighted
      images revealed three layers of different intensity. The area that demonstrated
      hypointensity on FLAIR images showed also hypointensity, while that in the area
      that demonstrated hyperintensity on FLAIR was divided into two parts; an area of
      isointense that encircles an hypointense area and a hyperintense area in the
      margin. The isointense and hypointense areas on diffusion-weighted images showed
      hyperintensity on apparent diffusion coefficient map. As JCV DNA was detected
      from his CSF, the diagnosis of PML was made. Based on comparative assessment of
      these MR images, it was speculated that the PML lesion appeared to be constituted
      of three parts from the margin to the center: cytotoxic edema, vasogenic edema,
      and liquefied lesion such as necrosis.

PMID- 15471090
TI  - [CT perfusion abnormalities in a case of non-herpetic acute limbic encephalitis].
AB  - We report a 42-year-old woman of non-herpetic acute limbic encephalitis (NHALE)
      whose CT perfusion (CTP) images revealed abnormalities of the limbic system at
      the early stage. The patient had high fever, convulsion and memory disturbance
      soon after having caught a common cold, and was admitted to a hospital where she
      developed progressive disturbance of consciousness. She was then transferred to
      our hospital 7 days after the initial manifestations. Although enhanced CT images
      of the brain failed to find any lesion, CTP images revealed a focal increase in
      the cerebral blood flow and shortening of mean transit time in the bilateral
      hippocampi and amygdalae. MRI of the subsequent day showed high signal intensity
      lesions on diffusion, T2-weighted and FLAIR images at the same area. Her
      consciousness improved by intravenous administration of high-dose
      methylprednisolone together with other combination therapies. Her CTP images
      apparently improved by 5 weeks after the onset, but she was left with mild memory
      disturbance, amenorrhea secondary to hypothalamic failure, hyperosmia, and
      hypogeusia. In conclusion, CTP is sensitive enough to detect the lesions of the
      limbic system even in the early stage of NHALE.

PMID- 15471091
TI  - [A case of middle-aged onset sialidosis type I].
AB  - We reported a patient with middle-aged onset sialidosis type I. A 52-year-old
      Japanese man was referred to our hospital because of dysarthria, involuntary
      movement of his extremities and gait disturbance since the age of 46 years. On
      admission, neurological examination revealed scanning speech, action myoclonus,
      cerebellar ataxia and cherry-red spots. Vacuolated lymphocytes were found in
      peripheral blood. Brain 18F-2-fluoro-2-deoxy-D-glucose positron emission
      tomography (18F-FDG PET) showed decreased glucose metabolism in the cerebellum.
      Enzymological analysis using his skin fibroblasts revealed primary deficiency of
      sialidase activity. Sialidase gene analysis identified compound heterozygotes for
      base substitusions of 239T-to-C and 649G-to-A, which resulted in amino acid
      alterations of P80L and V217M, respectively. These mutations have been reported
      in Japanese sialidosis type II (P80L) and I (V217M). Further studies are required
      to reveal effects of gene mutations on residual enzyme activities and phenotypes.

PMID- 15471092
TI  - [Decerebrate rigidity after bilateral carotid arteries occlusion].
AB  - We reported a 77-year-old woman with atrial fibrillation. She was admitted to our
      hospital because of bradycardia and disturbance of consciousness. She regained
      consciousness soon after the admission, however on the 3rd day of admission, she
      abruptly fell into a coma. Neurological examination revealed decerebrate
      rigidity, conjugate eye deviation to the right, and bilateral Babinski signs, but
      remaining oculocephalic reflex in both vertical and horizontal directions.
      Diffusion-weighed MR image of the brain on the same day demonstrated extensive
      hyperintense lesions in the bilateral hemispheres, sparing the brainstem. On the
      duplex carotid ultrasonography just after the MR study, oscillating intraluminal
      thrombi occluded the right common carotid and the left internal carotid artery.
      We diagnosed the patient as having bilateral carotid occlusions by cardioembolic
      mechanism.

PMID- 15471093
TI  - [A variant of Guillain-Barre syndrome with prominent bilateral peripheral facial
      nerve palsy--facial diplegia and paresthesias].
AB  - A patient with Facial diplegia and paresthesias, a rare regional variant of
      Guillain-Barre syndrome (GBS), is described. A 37-year-old woman developed
      paresthesias in the distal limbs and subsequently bifacial weakness. She had had
      a preceding episode of laryngitis. Neurological examination showed severe facial
      diplegia with loss of taste sensation on the tip of the tongue. Limb muscle power
      was preserved. Deep tendon reflexes were generally absent. She complained of
      paresthesias in the distal limbs, but sensory examination was normal.
      Cerebrospinal fluid showed albuminocytological dissociation. Electrophysiological
      studies revealed severe facial nerve involvements and demyelinative findings in
      her limbs. Intravenous immunoglobulin rapidly improved the abnormal sensation in
      her limbs. Although facial diplegia gradually lessened after the therapy, mild
      residual weakness was noted 6 months after the neurological onset. To diagnose
      facial diplegia and paresthesias, it is important to clarify the findings common
      to typical GBS such as the antecedent illness, acute and monophasic course,
      distal paresthesias, areflexia, cerebrospinal fluid albuminocytological
      dissociation, and demyelinative conduction abnormalities in the limbs.

PMID- 15471094
TI  - Use of biomarkers to characterize functions of polymorphic DNA repair genotypes.
AB  - Inheritance of variant DNA repair genes is believed to influence individual
      susceptibility to the development of environmental cancer. However, the validity
      of the belief is dependent upon understanding the functions of the variant genes.
      Consequently, a variety of studies have been conducted to investigate the
      functions of variant DNA repair genes, e.g. using biomarkers. These studies on
      several representative polymorphic DNA repair genes are reviewed in this report.
      From a general overview, it appears that the biomarker investigations did not
      provide consistent observations. However, from a more careful evaluation, it is
      clear that the inconsistencies are probably caused by the use of populations and
      biomarkers that are not appropriate for investigating the repair activities of
      the genes. For example, the use of cigarette smokers and patients may not
      generate precise information for this type of investigations because these
      conditions can modify the functions of the investigated genes. Thus, the use of
      healthy non-smokers would be more appropriate. Other problems with these studies
      includes the small sample size used and the fact that some of the biomarkers
      used, such as sister chromatid exchanges, are not appropriate because the
      mechanisms for formation of the biomarkers and their biological significance are
      unknown. Nevertheless, the following conclusions can be derived from the review
      of the various biomarker studies that have been published. XRCC1 194Trp, OGG1
      326Cys and APE1 148Glu probably have limited alterations in repair activities
      compared to the wild-type genotypes. XRCC1 399Gln and XRCC3 241Met are deficient
      in the repair of X-ray-, but not UV-light-induced chromosome aberrations,
      therefore the variant genes are defective in base excision repair. XPD 312Asn and
      XPD 751Gln are deficient in the repair of UV-light- but not X-ray-induced
      chromosome aberrations, therefore they are defective in nucleotide excision
      repair.

PMID- 15471095
TI  - Evidence for increased internal exposure to lower chlorinated polychlorinated
      biphenyls (PCB) in pupils attending a contaminated school.
AB  - External and internal exposure to six WHO-indicator congeners of polychlorinated
      biphenyls (PCB 28, 52, 101, 138, 153, 180) as well as subjective health
      complaints of a group of 377 pupils attending a PCB-contaminated school were
      compared with a control group of 218 pupils attending a non-contaminated school.
      Indoor air of the contaminated school revealed total PCB concentrations (sum of
      six indicator congeners times 5) ranging between 690 and 20,800 ng/m3 (median
      2044 ng/m3). The lower chlorinated congeners PCB 28, 52, 101 were the prevailing
      contaminants (median 33, 293, and 66 ng/m3). Using improved analytical procedures
      at least one of the lower chlorinated congeners could be detected in 95% of the
      blood samples of pupils attending the contaminated school. Median concentrations
      for PCB 28, 52, 101, and for the sum of lower chlorinated congeners were 6, 9, 5,
      and 22 ng/l blood plasma, respectively, whereas the corresponding values in the
      control group were all < 1 ng/l. In contrast, no significant differences were
      found for the higher chlorinated congeners (PCB 138, 153, 180) which were
      detected in 1-2 orders of magnitude higher concentrations in both groups. Due to
      the dietary intake of these congeners similar total PCB levels were found (95th
      percentile 1070 and 1010 ng/l plasma in participants of the contaminated and
      control school). Using the Giessen Subjective Complaint List for Children and
      Adolescents no statistically significant differences in health complaints were
      observed between both groups of children. It is concluded that exposure of pupils
      to PCB in indoor air of the contaminated school caused increased blood
      concentrations of lower chlorinated congeners. Compared to background levels the
      detected excess body burden was very low indicating no additional health risk.
      Exposure was not associated to any specific subjective complaints.

PMID- 15471096
TI  - Occupational exposure to polycyclic aromatic hydrocarbons suppresses constitutive
      expression of CYP1B1 on the transcript level in human leukocytes.
AB  - Expression patterns of the cytochromes P450 CYP1A1 and CYP1B1 have been analyzed
      on the transcript level in leukocytes of persons (n = 30) occupationally exposed
      to polycyclic aromatic hydrocarbons (PAH). To assess effects on expression levels
      results were compared with data obtained from a non-exposed control group (n =
      68). CYP1B1 transcripts can be detected in all subjects of the control group but
      vary largely in their levels (factor 35). Statistical analysis shows that this
      variability is neither due to the age of the persons nor due to cigarette
      smoking. Furthermore, there is no difference in expression levels between
      genders. In contrast to CYP1B1, CYP1A1 is detectable in only 14% of the subjects.
      People involved in graphite electrode production and exposed to PAH show largely
      decreased CYP1B1 transcript levels. In 67% of the subjects, CYP1B1 is no more
      detectable at all. Vice versa, expression of CYP1A1 is increased in exposed
      persons so that 80% become positive for CYP1A1 vs. 14% of the control group. The
      results show that occupational exposure to PAH apparently leads to effect
      relevant internal doses. Both, suppression of CYP1B1 and induction of CYP1A1 in
      leukocytes can be used as exposure parameters proving both enzymes to be suitable
      biomarkers of exposure. The suppression of CYP1B1 is an unexpected effect which
      needs further investigation. It is discussed that CYP1B1 and CYP1A1 indeed share
      a common Ah receptor mediated transcriptional regulation but that differences in
      promoter structure of the two genes and tissue-specific expression profiles of
      transcription factors may cause a differential expression behaviour.

PMID- 15471097
TI  - Nicotine and surface of particulates as indicators of exposure to environmental
      tobacco smoke in public places in Austria.
AB  - As part of a Europe-wide project the amount of exposure to environmental tobacco
      smoke (ETS) in public places like schools, restaurants, and public transport
      facilities was investigated. Three methods were applied: nicotine passive
      samplers (with a filter treated with sodium bisulphate), the same filters with an
      active sampling device, and the measurement of fine particles' active surface by
      unipolar diffusion charging. Settings were selected where either high or low ETS
      concentrations were expected and where non-smokers would have to stay or at least
      to pass by. Highest ETS concentrations were found in discos (mean nicotine
      concentration 154.4 maximum 487.1 microg/m3) and intermediate concentrations in
      restaurants with no significant difference between smoking (21.3 +/- 6.1
      microg/m3) and non-smoking areas (23.3 +/- 15.9 microg/m3) but on average higher
      values in restaurants with no separation between smoking and non-smoking areas
      (38.0 +/- 60.6 microg/m3). Concentrations usually below 10 microg/m3 were found
      in transport facilities (8.9 +/- 8.0 microg/m3, maximum 20.6 in the restaurant
      section of a railway station's waiting room) and in schools (3.0 +/- 4.6
      microg/m3). In hospitals "problem spots" were sought and so concentrations from
      very low to as high as 45.1 microg/m3 next to a smoking area with no physical
      barrier or separation and 47.7 microg/m3 inside a smoking room could be
      documented (21.4 +/- 39.3 microg/m3). The fine particle's surface correlated well
      with the nicotine concentration (r = 0.8; p < 0.001). Only in one instance (in a
      pizza restaurant on a busy road with heavy duty diesel traffic and the sampling
      spot next to the pizza stove) high concentration of fine particles was detected
      without high nicotine. Tobacco smoke is a key source of indoor fine particles.
      Health policy must intervene to change the situation found at present in many
      public places in Austria.

PMID- 15471098
TI  - Content of lead in human hair from people with various exposure levels in
      Lithuania.
AB  - A study has been performed to estimate if hair lead (Pb) can be used assessing
      environmental and occupational exposure to the metal. From 1994-1997, 622 ceramic
      plant employees, 520 randomly selected controls from Kaunas without occupational
      exposure to Pb aged 18-64 years, and 380 10-13 year old children living in Kaunas
      participated in this study. The concentration of Pb in the hair samples was
      measured by atomic absorption spectrometry. The geometric mean of Pb in the hair
      of workers occupationally exposed to Pb was significantly higher than that in
      persons not exposed to the metal (7.6 microg/g, 95% CI = 6.5-8.7 for exposed
      workers, 3.2 microg/g, 95% CI = 2.8-3.6 for not exposed workers and 2.6 microg/g,
      95% CI = 2.4-2.9 for randomly selected controls, p < 0.05). Pb content in hair of
      boys and girls was 2.9 microg/g (95% CI = 2.6-3.3) and 3.1 microg/g (95% CI = 2.6
      3.6), respectively. Lead in hair was not related to gender. Multiple regression
      analysis in adults with age as a continuous variable showed a positive
      relationship between Pb in hair and age. Also different exposure levels were
      significantly related to Pb in hair. In men, a positive association was found
      between Pb in hair and smoking. The data obtained suggest that human hair could
      be used to identify lead exposure in epidemiological surveys.

PMID- 15471099
TI  - Biological effects of ultrafine model particles in human macrophages and
      epithelial cells in mono- and co-culture.
AB  - Exposure to elevated concentrations of ambient ultrafine particulate matter has
      been associated with increased morbidity and mortality in the public. The
      particle parameters triggering the underlying mechanisms are largely unknown. The
      aim of this study was to compare biological in vitro-effects of ultrafine model
      particles (hematite, silicasol) of different composition and different sizes to
      evaluate the influence of these parameters. Human epithelial (A549) and
      macrophage (THP-1, Mono Mac 6) cell lines in mono-culture as well as in co
      culture were used as cellular models. The uptake of hematite particles into A549
      cells was identified by light microscopy and confirmed by transmission electron
      microscopy. The loss of membrane integrity measured by the lactate dehydrogenase
      assay as well as the induction of interleukin-6 and interleukin-8 release were
      affected by the particles in a dose dependent manner. This study demonstrated
      that particle size and particle composition, respectively, were responsible for
      the observed biological effects. Furthermore, the co-cultures of epithelial cells
      (A549) and macrophages (Mono Mac 6 or differentiated THP-1) showed an increased
      sensitivity to particles concerning the cytokine release in comparison to the
      mono-cultures of each cell type.

PMID- 15471100
TI  - Well water--one source of Helicobacter pylori colonization.
AB  - Helicobacter pylori (H. pylori) is one of the world's most widespread
      microorganisms. Its acquisition in humans remains poorly understood, however,
      epidemiological studies have identified drinking water as reservoir for the
      bacterium. The aim of this study was to investigate the prevalence of H. pylori
      infection among individuals using or drinking previously H. pylori tested well
      water. Applying household cluster sampling, a total of 91 subjects, all using or
      drinking well water (13 of either H. pylori positive or negative wells), were
      screened for their H. pylori status. The group was comprised of 73 adults and 19
      children under the age of 18. H. pylori infection was determined using the
      [13C]urea breath test. A self-administered or parent-completed questionnaire
      provided information on living conditions and lifestyle habits including the use
      or drinking of well water. Logistic regression analyses associated the drinking
      of H. pylori positive well water with a positive colonization status [Odds Ratio
      (OR) 8.3; 95% confidence interval (95% CI) 2.4-29]. In summary, the use or
      drinking of H. pylori contaminated well water appears associated with the
      acquisition of a H. pylori infection. This study is based on a relatively small
      and inhomogeneous population sample and should be repeated to confirm the
      results.

PMID- 15471101
TI  - Indoor fungi levels in homes of children with and without allergy history.
AB  - A study was performed at the four sentinel health departments of Baden
      Wurttemberg between November 1999 and March 2000 to investigate the indoor levels
      of fungi at the homes of school children (mean age 10 y) and to describe possible
      associations with allergy statuses. Three hundred and ninety-seven households of
      school children with (n = 199) and without (n = 198) allergic history were
      included in the study. The median of colony forming units (CFU/m3) of fungi,
      measured in the children's bedrooms' in indoor air, was 105 (range 5 to 15,000),
      in outdoor air 110 (range 10 to 1500). The median of viable mould spores (CFU/g
      dust) in floor dust was 28,500 (range 1500 to 1,235,000), in mattresses 16,250
      (range 0 to 2,500,000). Neither climatological conditions, nor differences
      between urban and rural regions showed a systematic influence on fungi counts.
      There was no difference in concentrations and distribution of fungi species
      levels between children with and without allergic history. The sensitization rate
      against molds (IgE) was higher for children with allergic condition (9.2%) than
      in control children (4.4%), but there was no association with the fungi counts in
      the rooms. In conclusion, the study defined the mould levels in children's rooms,
      but did not find an association with allergic history of the children or their
      sensitization rate.

PMID- 15471102
TI  - Ergosterol as an indicator of mould growth on building materials.
AB  - Ergosterol was used as a specific indicator of fungal biomass to determine and
      assess mould growth on damp building material. The samples were saponified,
      cleaned up on a silica gel column and the sterols silylated and analysed by gas
      chromatography and mass spectrometry in MS/MS mode. Ninety-one samples of
      building materials from damp rooms were analysed including plaster,
      plaster/paint, paint, wood-chip wallpaper and paper wall covering. The
      concentrations of ergosterol ranged from 0.1 to 130 microg/g dry mass and
      depended on carbon content of the material. The highest concentrations were
      determined for wallpaper, the lowest for plaster and intermediate ones for paint.
      Based on ergosterol content and inspection of the room during sampling a rough
      classification of mould infestation is presented. The applicability of the
      ergosterol method was further tested in two case studies on the spatial
      distribution of fungi on damp walls and irregular distributions were found. With
      few exceptions the concentration of ergosterol in building materials was found to
      be a suitable indicator to estimate fungal biomass.

PMID- 15471103
TI  - Two episodes of vancomycin-resistant Enterococcus faecium outbreaks caused by two
      genetically different clones in a newborn intensive care unit.
AB  - In 2001 two outbreak episodes (January-March and June-July) caused by vancomycin
      resistant E. faecium (VRE) of the VanA-type were observed at a neonatal intensive
      care unit (NICU) of a university hospital in south-west Germany. To identify the
      initial source and the route of transmission environmental samples were examined
      as well as stool samples from patients and the staff. VRE was not found in
      environmental samples. However, stool samples from 24 hospitalised children
      tested positive and bacterial clonality was assessed by Sma1-based macro
      restriction analysis. Furthermore, esp gene and vancomycin resistance gene
      carriage were examined as well as bacteriocin production. PCR analysis showed
      that all 24 isolates carried vanA gene cluster, encoding resistance to vancomycin
      and teicoplanin. However, five of the vanA-positive isolates were resistant to
      vancomycin but not to teicoplanin. Only these five isolates produced bacteriocin,
      but in none of the isolates esp gene was detected. PFGE revealed that both
      outbreaks were caused by two different clones. The patient initiating the first
      episode, was identified whereas the origin of the second episode remained
      unknown. From one of the 40 staff stool samples VRE was isolated. This strain was
      related to the clone of the summer outbreak. In conclusion there were two
      independent episodes of self limiting VRE outbreaks and transmission on the ward
      is highly probable.

PMID- 15471104
TI  - Amalgam studies: disregarding basic principles of mercury toxicity.
AB  - Dental amalgam, which has been used for over 150 years in dental practice,
      consists of about 50% metallic mercury. Studies on animal and humans show that
      mercury is continuously released from dental amalgam and absorbed by several body
      tissues. It is widely accepted that the main source of mercury vapor is dental
      amalgam and it contributes substantially to mercury load in human body tissues.
      There is still a controversy about the consequences of this additional mercury
      exposure from amalgam to human health. Many studies were performed to evaluate
      possible adverse effects. In this comment, these studies were analyzed with
      regard to their methodical quality by considering the newest findings on mercury
      toxicity and metabolism. In sum, a number of studies are methodically flawed
      drawing inaccurate conclusions as to the safety of dental amalgam.

PMID- 15471105
TI  - Health effects of particles in ambient air.
AB  - A summary of a critical review by a working group of the German commission on Air
      Pollution Prevention of VDI and DIN of the actual data on exposure and health
      effects (excluding cancer) of fine particulate air pollution is presented.
      EXPOSURE: Typical ambient particle concentrations for PM10 (PM2.5) in Germany are
      in the range of 10-45 (10-30) microg/m3 as annual mean and 50-200 (40-150)
      microg/m3 as maximum daily mean. The ratio of PM2.5/PM10 generally amounts
      between 0.7 and 0.9. HEALTH EFFECTS: During the past 10 years many new
      epidemiological and toxicological studies on health effects of particulate matter
      (PM) have been published. In summary, long-term exposure against PM for years or
      decades is associated with elevated total, cardiovascular, and infant mortality.
      With respect to morbidity, respiratory symptoms, lung growth, and function of the
      immune system are affected. Short-term studies show consistant associations of
      exposure to daily concentrations of PM with mortality and morbidity on the same
      day or the subsequent days. Patients with asthma, COPD, pneumonia, and other
      respiratory diseases as well as patients with cardio-vascular diseases and
      diabetes are especially affected. The strongest associations are found for PM2.5
      followed by PM10, with no indication of a threshold value for the health effects.
      The data base for ultra fine particles is too small for final conclusions. The
      available toxicological data support the epidemiological findings and give hints
      as to the mechanisms of the effects. CONCLUSION: The working group concludes that
      a further reduction of the limit values proposed for 2005 will substantially
      reduce health risks due to particulate air pollution. Because of the strong
      correlation of PM10 with PM2.5 at most German sites there is no specific need for
      limit values of PM2.5 for Germany in addition to those of PM10.

PMID- 15471106
TI  - Cost burden of hip and knee replacements in Ohio: estimates from the National
      Hospital Discharge Survey, 2000.
AB  - This study estimated the number of arthritis-related hip/knee replacements
      performed in the nation as well as in Ohio. These estimates were then used to
      calculate the economic burden associated with arthritis-related surgeries. The
      National Hospital Discharge Survey in 2000 and the 2000 U.S. Census were utilized
      to estimate the number and cost of hip/knee replacements performed. In the United
      States, approximately 9.9 billion dollars was spent on 439,833 hip/knee
      replacement surgeries in the year 2000. In Ohio, approximately 420 million
      dollars was spent for 18,731 hip/knee replacement surgeries. The true cost of
      arthritis in terms of joint replacement is estimated to be much higher if
      preoperative and postoperative care is included.

PMID- 15471107
TI  - Using the Internet for disease management: who do we reach?

PMID- 15471108
TI  - Assessing stage of change and informed decision making for Internet participation
      in health promotion and disease management.
AB  - The Internet is a potentially powerful source of low- or no-cost programs through
      which individuals can be guided in changing their behavior to improve health.
      Using the Transtheoretical Model and survey methodology, the authors sought to
      produce reliable and valid instruments for assessing "stage of change" and
      "informed decision making," and to generate cross-sectional and longitudinal
      stage-of-change data for a sample of Internet users, as they apply to Internet
      use for health promotion and disease management. They found that only 24.7% of
      their sample used the Internet for these purposes and concluded that considerably
      more research will be needed to determine how to help significant percentages of
      populations to progress toward enhancing their health through the Internet.

PMID- 15471109
TI  - Is the market ready for direct pharmaceutical contracting by employers?

PMID- 15471110
TI  - Economic effect of cholinesterase inhibitor therapy: implications for managed
      care.
AB  - The growing elderly population is at great risk for Alzheimer's disease (AD). In
      1997, annual costs associated with AD were 100 billion dollars. Cholinesterase
      inhibitor (ChEI) therapy is most commonly used to manage patients with AD, but
      the economic implications arising from their use are not well known. A review of
      studies assessing the cost effectiveness of ChEIs suggests that ChEI therapy
      provides benefit at every stage of disease, with better outcomes resulting from
      persistent, uninterrupted treatment. The cost savings range from 73 dollars over
      two years to 3891 dollars over one year, depending on the type of study, drug
      evaluated, and economic model employed in the evaluation.

PMID- 15471111
TI  - Prompt-pay legislation: is it a solution?
AB  - Prompt-pay laws, whose purpose is to ensure prompt and equitable settlement of
      health care claims, have been enacted in 48 states and the District of Columbia.
      The laws were enacted in reaction to the growth of managed care plans, despite
      the fact they apply to all health plans. Are they working? The author explores
      this question in the context of New York State, although the lessons learned may
      be applied to any jurisdiction in which these statutes have been enacted.

PMID- 15471112
TI  - Ki-67 immunostaining in Pap smears of cervix: assessment of proliferation in
      preinvasive and invasive squamous epithelial lesions.
AB  - Ki-67 is a novel proliferation marker. Its use has been extensively studied in
      biopsy sections of preinvasive and invasive squamous epithelial lesions of
      cervix. However, only limited work has been done on its application on Pap smears
      of cervix. We applied Ki-67 immunostaining on cytology smears of various grades
      of squamous epithelial lesions of cervix. Sixty cases were chosen for
      immunostaining by Peroxidase antiperoxidase method using DAB as a chromogen. High
      level of Ki-67 labelled proliferation was measured in squamous cell carcinomas of
      cervix. Statistically significant difference was observed between preinvasive and
      invasive squamous epithelial lesions of cervix. Ki-67 could prove as a useful
      adjunctive test to routine Pap smear in triage of patients harboring lesions of
      cervix.

PMID- 15471113
TI  - Intestinal neuronal disorders--a study of seven cases.
AB  - Intestinal neuronal dysplasia (IND) has been reported as an innervation disorder
      that can present as isolated disease or may be associated with Hirschsprung's
      disease (HD). The interest in this disorder is growing as it mimics HD at
      clinical level but can be managed with a more conservative approach if an
      accurate diagnosis can be made. Many workers have tried to set up diagnostic
      criteria of this condition. But the importance of one criterion varied from one
      study to another. In our study we analysed seven cases of suspected innervation
      disorder that had undergone resection. A detailed histological study on these
      cases was performed and four of them were found to fulfill the diagnostic
      criteria of IND laid down by Kobayashi and his co-workers. These patients had
      hyperganglionosis, giant ganglia and ectopic ganglion cells in the lamina
      propria. In the other three cases some features were highly suggestive of the
      diagnosis of the IND and can be considered to be so if we follow other workers
      who have not given much importance to the simultaneous presence of all three
      criteria in a single case.

PMID- 15471114
TI  - Rapid rescreening of cervical smears by cytopathologists: experience at a WHO
      collaborating centre for research in cytology.
AB  - The conventional 10% random full rescreening of cervical smears has been
      criticized as a quality assurance measure as it is not scientifically based and
      tends to detect only a few false negative cases. Rapid rescreening (RR) of
      negative cervical smears seems to be a viable alternative, especially in
      developing countries, as it picks up more positive lesions, reduces the false
      negative rate and is cost effective. We performed rapid review on 12374 cervical
      smears received under a hospital based cervical cancer screening programme. An
      additional 498 lesions were picked up on RR including a sizeable number of low
      and high grade lesions as well as 2 malignant cases. Thus RR led to an increase
      in efficiency of our laboratory.

PMID- 15471115
TI  - Immunohistochemical detection of serum autoantibodies--a new technique using
      routine formalin fixed paraffin sections.
AB  - Detection of autoantibodies in serum is important in the diagnosis of primary
      immune mediated diseases. Tests of these antibodies are conventionally done by
      indirect immunoflourescence (IIF) on frozen sections of fresh target tissues from
      the murine species. More recently enzyme-linked immunoassays and IIF on cultured
      human epithelial cells or on fresh frozen sections of murine tissues coated onto
      wells or glass slides are also being used. But these tests are more expensive and
      generally not easily available to laboratories in developing countries. Obtaining
      small animals for preparing frozen sections of fresh tissue is also getting to be
      increasingly difficult. A simple; new and inexpensive technique was developed to
      perform IIF on routine paraffin sections of human tissues following antigen
      unmasking. This, technique offers qualitatively good, consistent, species
      specific and dependable results with several advantages over the conventional IIF
      on animal tissue frozen sections, particularly in a sausage block made from
      different types of tissues. Immunoperoxidase stain for autoantibodies can also be
      easily performed with the advantages of permanent preservation and clearer
      evaluation in light microscopy. Most importantly the technique is easily
      affordable and practicable in all histopathology laboratories.

PMID- 15471116
TI  - Goblet cell status in idiopathic ulcerative colitis--implication in surveillance
      program.
AB  - Idiopathic ulcerative colitis (IUC) patients have higher incidence of dysplasia
      and malignancy. Close follow-up with biopsy at regular interval is mandatory. The
      study was done to correlate incidence of atypical epithelium, goblet cell
      hyperplasia (GCH) and disease duration (DD) with Ki67, AgNOR and p53 expression
      in IUC with disease for 5 or more years. Ki67 and AgNOR are good indicators of
      cellular proliferation and p53 tumour suppressor protein is a marker for
      neoplastic cell. Of 130 cases studied, 40 cases showed atypical epithelium and
      were selected for further study. DD in these 40 cases ranged from 60 to 228
      months. All had GCH and showed histological features of chronicity. Low-grade
      dysplasia (LGD) was seen in 15 cases, indefinite for dysplasia (ID) in 8 and
      inflammatory atypia in 17 cases. Disease duration showed no influence in the type
      of atypical epithelium. A positive staining of lining epithelium by Ki67 and p53
      was not restricted to dysplasia. LGD and ID showed stronger p53 nuclear staining.
      AgNOR appeared to be a more sensitive marker than Ki67. GCH showed a positive
      correlation with DD and AgNOR index. p53 expression correlated positively with
      goblet cell hyperplasia. Conclusion- goblet cell hyperplasia could indicate
      presence of epithelial cell dysplasia.

PMID- 15471117
TI  - Melanin containing cells of the uterine cervix and a possible histogenesis--a
      case report.
AB  - A 30 year old nulligravidfemale attended gynaecological OPD for investigation of
      primary infertility. Local examination revealed presence of a dark pigmented area
      in the posterior lip of the cervix. The biopsy from cervix showed, squamous
      metaplasia of the lining epithelium with presence of granules of melanin pigment
      in the basal layer. Schmorl's stain for melanin and immunohistochemical staining
      for S-100 and HMB-45 showed strong positivity in these cells. Melanosis of the
      uterine cervix is usually an incidental finding in females with uterine prolapse
      in their fifth and sixth decade. The origin of melanin containing cells in the
      uterine cervix is debatable till date. Amongst the various possibilities for the
      origin of these cells in the uterine cervix, neural origin is probably more
      acceptable than epithelial cell origin. The combined expression of melanocytic
      and Schwanian markers in the index case, suggest a biphasic differentiation of
      melanin containing cells in the uterine cervix. Although the exact histogenesis
      and clinical significance of these are still unknown, a long term follow-up is
      needed to study the nature of these lesions to look for any precursor lesion for
      development of malignant melanoma.

PMID- 15471118
TI  - Isolated nocardial subcapsular and perinephric abscess.
AB  - We report a rare presentation of Nocardia infection in a 60 years old diabetic
      and cirrhotic patient who had perinephric and subcapsular renal abscess. This
      localized type of infection was successfully treated with oral cotrimoxazole.

PMID- 15471119
TI  - Fibrosarcomatous Bednar tumor with distant metastases--a case report.
AB  - In July 1994, a 27 year-old man presented with a twice recurrent, pigmented tumor
      on his left wrist. Wide excision and histological examination showed a pigmented
      dermatofibrosarcoma protuberans (PDFSP) or Bednar tumor with foci of
      fibrosarcomatous (FS) change. Immunohistochemistry helped to distinguish it from
      cellular blue nevus and malignant melanoma. In January 1997, he presented with 3
      swellings on his thighs which showed features of fibrosarcoma. In March 1998, he
      developed multiple tumors on his thighs, chest wall, supraclavicular region,
      parapharyngeal region and two lung nodules. To the best of our knowledge, there
      are only 3 previously published reports of metastases in patients with Bednar
      tumor. We present the fourth such case.

PMID- 15471120
TI  - Congenital cystic adenomatoid malformation of lung--report of three cases.
AB  - Congenital cystic adenomatoid malformation (CCAM) of the lung is a rare anomaly
      of fetal development of terminal respiratory structures. We report three cases of
      congenital cystic adenomatoid malformation (CCAM) of lung Stocker's type I. All
      the cases presented with progressive neonatal respiratory distress. One case
      developed hyaline membrane because of ventilator therapy. No other congenital
      malformation was found in any of our cases. Two of our cases were suspected on
      antenatal ultrasonography. Routine prenatal ultrasonography has increased the
      frequency of prenatal diagnosis of congenital cystic lung malformation including
      CCAM. The pathogenesis, management and prognosis of CCAM are discussed along with
      a review of literature.

PMID- 15471121
TI  - Presacral carcinoid tumour arising in a tailgut cyst--a case report.
AB  - Primary carcinoid tumours of the presacral region are extremely infrequent with
      just a handful of such cases reported in literature. Tailgut cysts(retrorectal
      cystic hamartoma) are also very uncommon lesions which are usually identified in
      adult life. They are developmental abnormalities and consist of multiloculated
      cysts lined by squamous, transitional or glandular epithelium. Malignant
      transformation within tailgut cysts is rare; the tumours which arise include
      carcinoid tumours and adenocarcinomas. We report the unusual occurrence of a
      carcinoid tumour developing within a tailgut cyst.

PMID- 15471122
TI  - Rosette formation in non Hodgkin's lymphoma in the bone marrow--a case report.
AB  - This is a case report of rosette formation in non-Hodgkin's lymphoma in the bone
      marrow. A 66 year old female on treatment for metastatic papillary carcinoma
      thyroid and non-Hodgkin's lymphoma of the nodular small cleaved cell type was
      found to have bone marrow infiltration by a low grade B cell lymphoma. Bone
      marrow aspirate, imprint and trephine biopsy showed rosettes of the abnormal
      lymphoid cells. The associations of papillary carcinoma thyroid,
      hyperglobulinemia and retroperitoneal fibrosis in this case which explain the
      histogenesis of rosette formation are discussed.

PMID- 15471123
TI  - Xanthogranulomatous pancreatitis: mass lesion of the pancreas simulating
      pancreatic carcinoma--a report of two cases.
AB  - Xathogranulomatous inflammation is well known in the gall bladder and kidney.
      Xanthogranulomatous pancreatitis has not been previously described. We report two
      cases of this new clinicopathologic entity. The first was a 50 years old male
      with cholelithiasis and progressive obstructive jaundice for 5 months. Radiology
      was suggestive of carcinoma head of pancreas and a Whipples procedure was
      performed. The second was a 36 years old male with choledocholithiasis and
      features of chronic pancreatitis. During pancreaticojejunostomy, a mass was found
      in the tail of pancreas, which was excised with a suspicion of carcinoma. Gross
      examination of both specimens showed firm grey white masses, demarcated from the
      surrounding pancreas but with infiltrative margins, and were thought to be
      carcinoma. Histopathological examination showed localized inflammation with
      numerous foamy histiocytes along with dilated ducts and microabscesses. A
      diagnosis of xanthogranulomatous pancreatitis was made in both instances. In view
      of clinical, radiological, operative and gross appearances of our cases
      simulating carcinoma, recognition of xanthogranulomatous chronic pancreatitis as
      a distinct clinicopathological entity seems important, analogous to similar
      lesions of the kidney and gall bladder.

PMID- 15471124
TI  - Water-clear cell adenoma of the parathyroid gland: a rare entity.
AB  - Water-clear cell hyperplasia is a rare but well-documented cause of primary
      hyperparathyroidism. Parathyroid adenomas of water-clear cell type are
      exceptionally rare, and only five case reports are available at present in the
      medical literature. We report an additional case of water-clear cell adenoma of
      the parathyroid gland, and the differential diagnoses are discussed.

PMID- 15471125
TI  - Recurrent diffuse lipomatosis of the neck--a case report.
AB  - Diffuse lipomatosis is a rare disorder of adipose tissue occurring in young
      people . It has a predilection for trunk and proximal extremities where it
      presents as poorly circumscribed overgrowth of fatty tissue. Definite diagnosis
      is established by histological examination of tumor. Though it attains extensive
      size and has a high tendency to recur, the clinical course is benign.

PMID- 15471126
TI  - Transformation of solitary osteochondroma calcaneum to chondrosarcoma--a case
      report.
AB  - Solitary osteochondroma of calcaneum is an uncommon benign tumor. Its malignant
      transformation to chondrosarcoma is rarely encountered. Pain and recent
      enlargement are clinical manifestations of this complication. Magnetic resonance
      imaging is a valuable tool to detect this change.

PMID- 15471127
TI  - Adrenocortical carcinoma: diagnosis by fine needle aspiration cytology.
AB  - Two cases of adrenal cortical carcinoma are described, wherein the diagnosis was
      established by fine needle aspiration cytology (FNAC). FNAC is increasingly being
      accepted as a means of diagnosis of adrenal cortical carcinomas. In yester years
      the diagnosis was established largely on post-operative histopathology. Adrenal
      cortical carcinomas are rare and account for less than 0.05% of all malignant
      neoplasms. Adrenal gland has become frequent target of needle biopsies with the
      availability of sensitive imaging techniques and better localization. Currently,
      needle biopsy is the only non-surgical means of obtaining a diagnosis in patient
      with adrenal mass. We present two cases of adrenal cortical carcinoma diagnosed
      on fine needle aspiration cytology (FNAC).

PMID- 15471128
TI  - Dedifferentiated chondrosarcoma--an unusual presentation: a case report.

PMID- 15471129
TI  - Congenital transient myeloproliferative disorder progressing to acute myeloid
      leukemia in Down's syndrome: a case report.
AB  - Chromosomal abnormalities like monosomies and trisomies predispose to various
      malignancies, hematopoietic or non hematopoietic. Patients with Trisomy 21(Down's
      syndrome) are prone to acute leukemias during childhood, but congenital leukemia
      in such children is rare (17%) and should be differentiated from a similar
      condition -Transient Myeloproliferative Disorder (TMD) which does not necessitate
      any treatment other than follow up. We report a patient of Down's syndrome with
      TMD in neonatal period which had spontaneous remission at 3 weeks but later died
      of acute myeloid leukemia at 6 months. The blasts in our case during the TMD
      episode were Myeloperoxidase(MPO) positive unlike other cases of TMD reported in
      literature. To the best of our knowledge we have not come across a case of TMD
      (MPO positive) later progressing to leukemia in Indian literature. Hence we
      report this case.

PMID- 15471130
TI  - Gamna Gandy bodies of spleen seen in CML: a causal association--a case report.
AB  - Gamna Gandy bodies are usually seen in spleen in cases of chronic venous
      congestion. We present a case of CML showing gamna gandy bodies. These may have
      occurred as a part of evolving portal hypertension which maybe due to
      antileukemic therapy or CML per se or due to a combination of both factors.

PMID- 15471131
TI  - Bilateral total renal dysplasia: a case report.
AB  - Bilateral total renal dysplasia is an extremely rare congenital anomaly
      associated with Potter's facies. We report an autopsy case of a stillborn male
      child. Histopathology is showing persistence of structures not seen in normal
      development.

PMID- 15471132
TI  - Malignant melanoma of soft parts a diagnostic pitfall in FNA: a case report.
AB  - Malignant melanoma of soft parts (MMSP) is a rare tumour with frequent local
      recurrences and eventual nodal and distant metastasis. It has characteristic
      clinical features and histologic picture. However, a precise diagnosis of this
      tumor may be difficult on aspiration material. We report two cases of MMSP which
      posed a diagnostic dilemma owing to their variable cytomorphological features and
      make an attempt to review the literature.

PMID- 15471133
TI  - Leiomyosarcoma of the urinary bladder: a case report.
AB  - A case of leiomyosarcoma of the urinary bladder occurring in a middle aged lady
      with immunohistochemical confirmation is presented for its rarity with emphasis
      on grading of smooth muscle neoplasms of the urinary bladder.

PMID- 15471134
TI  - Left shoulder region metastasis from hepatocellular carcinoma as an initial
      presentation--a case report.
AB  - Hepatocellular carcinoma metastasis as a soft tissue mass is rare; we came across
      a 65 years old female who presented with a left shoulder region mass. There was
      no previous history of any liver disease and liver function tests were normal.
      Histologically, it turned out to be a metastasis from hepatocellular carcinoma.

PMID- 15471135
TI  - The TACRD association is distinct from VACTERL association--a case report.
AB  - Tracheal agenesis is a rare malformation. A case of tracheal agenesis with
      associated ventricular septal defect, gastric hypoplasia, hiatus hernia, duodenal
      atresia, isomerism of the lungs, hypoplastic spleen with polysplenia, Meckel's
      diverticulum and fused crossed ectopia of the kidneys is presented. This case
      fits into a newly proposed TACRD association, an extremely rare condition
      composed of tracheal agenesis, cardiac, renal and duodenal malformations. It is
      distinct from the more common VACTERL association of which tracheo-esophageal
      fistula and not tracheal agenesis is a part. TACRD association has complex
      internal malformations and lacks the external skeletal manifestations of VACTERL
      association. Awareness amongst pathologists conducting neonatal autopsies is
      necessary for correct identification of this condition.

PMID- 15471136
TI  - True malignant mixed tumor (carcinosarcoma) of parotid gland : a case report.
AB  - The malignant mixed tumor (carcinosarcoma) of the salivary gland is an extremely
      rare tumor. By definition, it is composed of both malignant epithelial and
      malignant mesenchymal components. We report a case of carcinosarcoma in the
      parotid gland of a 59 year old man, that arose "de novo" and contained ductal
      adenocarcinoma as the epithelial component and osteosarcoma and chondrosarcoma as
      mesenchymal components. The etiologic and histologic features are presented and
      in addition, the literature is reviewed.

PMID- 15471137
TI  - Bilateral granulocytic sarcoma (chloroma) of the breast in CML in blast crisis: a
      case report.
AB  - A 35 year old lady was diagnosed as having chronic myeloid leukemia in May 1999
      and thereafter started on chemotherapy. Three years later the patient presented
      with bilateral breast masses. FNAC from both the breast lesions showed leukemic
      infiltration (granulocytic sarcoma). The peripheral blood picture showed blastic
      transformation. Breast is an uncommon site for development of granulocytic
      sarcoma. We present this case because of its unusual location and bilateral
      nature.

PMID- 15471138
TI  - Rosette formation in osteosarcoma.
AB  - Rosette formation is a rare, recently reported variation in osteogenic sarcoma
      and is thought to be associated with a poor prognosis. We report two cases of
      rosette forming osteosarcoma, one with poor response and other with total
      necrosis following chemotherapy. Pathologists should be aware of rosette
      formation in osteosarcoma to avoid misdiagnosis as other rosette forming tumors
      of bone especially PNET/Ewings sarcoma. In our opinion rosettes in an
      osteosarcoma should be documented both from a differential diagnostic point of
      view and also to elucidate definitive prognostic implications.

PMID- 15471139
TI  - Transitional cell carcinoma of uterine cervix complicated by pyometra.
AB  - Transitional cell carcinoma of cervix is a rare neoplasm of recent description. A
      case of primary transitional cell carcinoma of female genital tract i.e. uterine
      cervix in a 60 year-old postmenopausal female complicated by pyometra is
      reported.

PMID- 15471140
TI  - Adenosquamous carcinoma of the rectum: a case report.
AB  - Adenosquamous carcinoma is defined as a tumor with well defined malignant
      glandular and squamous components and the potential for both components to
      metastases. This tumor is extremely rare in colon and rectum with an incidence of
      less than 0.2%. Adenosquamous carcinoma of rectum should be distinguished from
      collision tumor with exemption of all lesions located distal to a level of 7 cm
      above the dentate line. Here we present a case of rare type adenosquamous
      carcinoma in rectum in a 29 year old female.

PMID- 15471141
TI  - Pleural empyema due to S. typhi: a case report.
AB  - In a 35 year old immunocompetent male, clinically diagnosed as a case of
      hydropneumothorax of left side, Salmonella typhi was isolated as the causative
      agent of pleural empyema.

PMID- 15471142
TI  - Infective endocarditis due to Salmonella typhi--a case report.
AB  - Endocarditis is a rare complication of typhoid fever. We report a case in which
      Salmonella enterica serotype typhi was isolated from a case of endocarditis. The
      isolate was resistant to ampicillin, chloramphenicol and ciprofloxacin but
      sensitive to ceftriaxone, amikacin and gentamicin.

PMID- 15471143
TI  - Persistence of parvovirus B19 IgM antibodies and DNA in pure red cell aplasia
      resulting in myelodysplasia--a case report.
AB  - Human erythrovirus B19 (B19), previously known as parvovirus B19, is a small
      spherical, non-enveloped single stranded DNA virus. It has been shown to cause a
      wide spectrum of clinical conditons including various hematological disorders. We
      report here for the first time from Inida a case of pure red cell aplasia in a 45
      year-old female for last 7 years due to chronic persistent B19 infection leading
      to myelodysplasia after 4 years. Her sera were positive for two times 4 months
      apart for B19 IgM and B19 DNA at the initial stage. Presently the patient is on
      repeated blood transfusion on every 15-20 days.

PMID- 15471144
TI  - Correlation of extended spectrum beta lactamases production with cephalosporin
      resistance in gram negative bacilli.
AB  - Beta lactamase production is an important mechanism of developing resistance to
      beta lactam group of antibiotics. Cephlosporins with extended spectrum of
      activity and stability were introduced to overcome this resistance, but soon
      production of extended spectrum beta lactamases (ESBLs), which are inducible in
      nature was reported. In this study Klebsiella aerogenes--166, Escherichia coli-
      120, Citrobacter spps--116, Pseudomonas spps--50, Proteus spps--32 and S. typhi-
      16, strains were subjected to sensitivity testing against various generations of
      cephalosporins by disc diffusion method and for the production of ESBLs using
      disc approximation method. Klebsiella aerogenes, Escherichia coli, Citrobacter
      spps and Pseudomonas spps showed statistically significant difference in the
      resistance pattern to all three generations of cephalosporins and ESBLs
      production.

PMID- 15471145
TI  - Detection of slime production by coagulase-negative Staphylococcus: an assessment
      of two methods.
AB  - The detection of slime can be helpful in determining the diagnostic value of
      coagulase-negative Staphylococcus (CNS). Here, we have made a comparative study
      of two phenotypic methods of slime production test from 28 clinically significant
      blood culture isolates of CNS. A total 16 out of 28 isolates (57.1%) were
      positive for slime by either of the tests, whereas only 5 out of 28 isolates
      (17.9%) were positive for slime by both the tests. The tube method detected slime
      in significantly more number of isolates than the spectrophotometric method (14
      vs. 7; p<0.0483279). A weak correlation was found between the tube method and the
      spectrophotometric method (rs=0.2474). The tube test was found to be superior to
      the spectrophotometric test in terms of sensitivity, ease of performance and
      interpretation, and cost effectiveness.

PMID- 15471146
TI  - Molecular epidemiology of rotavirus in Delhi.
AB  - Rotavirus is now established as an important cause of childhood diarrhoea
      throughout the world. Despite the availability of more advanced techniques for
      HRV characterization, electropherotyping was employed in this study to
      demonstrate the occurrence of diverse electropherotypes & any aberrant types
      thereof in isolates from children with acute gastroenteritis in Delhi, keeping in
      mind the ease of availability, performance and discriminatory power. Faecal
      specimens from 1172 children suffering from acute gastroenteritis were subjected
      to enzyme linked immunosorbent assay (ELISA) and polyacrylamide gel
      electrophoresis (PAGE). A total of 158 rotavirus strains were detected and
      electropherotyped by PAGE. Rotavirus was detected in 13.48% of the samples. A
      total of 10 electropherotypic patterns were observed to be in circulation. There
      was predominance of the long type over the short type and long type G was the
      most common isolate. The present study highlights the simultaneous coexistence of
      different electropherotypes of Human rotavirus strains circulating in Delhi and
      stresses the need for constant monitoring of the genomic diversity resulting from
      extensive genomic variation among Rotaviruses.

PMID- 15471147
TI  - [Importance of spinal cord stimulation in the treatment of refractory angina].
AB  - A small non-quantified number of patients is reported to be affected by forms of
      angina pectoris already treated by traditional therapy but no longer able to
      achieve better results by drugs or surgery: this is called "refractory angina".
      Treatments like external counterpulsation, transmyocardial laser
      revascularization, stem cell transplantation or spinal cord stimulation may be
      suitable for these patients. The analysis of major studies on spinal cord
      stimulation based on exercise ECG, Holter monitoring and positron emission
      tomography, has shown a reduction in anginal attacks and in nitroglycerin pills.
      Though in small figures, an improved perfusion of the ischemic areas, an increase
      in the time of ischemia and cardiac mortality comparable to bypass surgery as
      well as a better quality of life and lower costs with respect to traditional
      treatment are also evident. Patients who are at high risk of mortality for bypass
      surgery, and who cannot receive significant benefits from revascularization or
      improved pharmacological therapy are candidate to spinal cord stimulation. Spinal
      cord stimulation is safe and effective in about 70% of patients. Some issues have
      not been investigated yet: the clinical characteristics of "non-responders" and
      the possibility of avoiding sudden cardiac death in stimulated patients.

PMID- 15471148
TI  - [Hypertension, dyslipidemia and cardiovascular risk in chronic renal disease].
AB  - Cardiovascular disease is the major cause of morbidity and mortality in patients
      with chronic kidney disease (CKD). The presence of CKD whether manifested by
      albuminuria or reduction in glomerular filtration rate is an independent risk
      factor for cardiovascular outcome. This is mainly due to both an overexpression
      of traditional cardiovascular risk factors, and the onset of new factors which
      are peculiar of CKD. In this revision the role of arterial hypertension and of
      dyslipidemia is analyzed in detail. Most interventional trials have demonstrated
      that a reduction of blood pressure and the normalization of lipid profile are
      associated with a significant reduction in the incidence of major cardiovascular
      events and mortality. According to the National Kidney Foundation-Kidney Disease
      Outcomes Quality Initiative (NKF-K/DOQI) recommendations, patients with CKD,
      regardless of the stage of disease, should be considered the highest risk group
      for cardiovascular events. For these patients the NKF-K/DOQI guidelines recommend
      strict blood pressure control, renin-angiotensin system blockade, and the use of
      statins with target LDL cholesterol levels < 100 mg/dl.

PMID- 15471149
TI  - [Cardiac resynchronization therapy for heart failure].
AB  - The short-term prognosis of advanced refractory heart failure is extremely poor
      and closely correlated with progressive left ventricular dysfunction. The
      identification of the negative effects of conduction delay on cardiac
      performance, observed in almost 50% of heart failure patients, disclosed a new
      research field addressing the correction of electrical abnormalities in order to
      achieve an improvement in myocardial function. Biventricular stimulation, or
      cardiac resynchronization therapy, corrects the atrioventricular, inter- and
      intraventricular mechanical asynchrony and, to date, is indicated (class IIA,
      level of evidence A) for patients with NYHA class III-IV refractory heart failure
      regardless of its etiology, QRS interval > or = 130 ms, left ventricular end
      diastolic diameter > or = 55 mm, and ejection fraction < or = 35%. To date, the
      completed trials demonstrated in patients undergoing biventricular pacing a
      significant improvement in left ventricular performance, quality of life and NYHA
      class with no significant effects on total mortality. The identification of non
      responders (approximately 20-30% of the patient population in completed trials)
      represents an unresolved issue of cardiac resynchronization therapy. Tissue
      Doppler imaging evaluation of left ventricular dyssynchrony, which is being
      addressed by non-randomized prospective studies, should drastically decrease the
      percentage of these patients.

PMID- 15471150
TI  - [Echocardiography in aortic stenosis: new insights into challenging scenarios].
AB  - The natural history of aortic stenosis is well defined. There is overwhelming
      evidence that patients with this disease who develop symptoms require prompt
      aortic valve replacement, as average survival rapidly falls. Once surgery has
      been performed age-corrected rates of survival approach the rate in the normal
      population. Conversely, asymptomatic patients with severe aortic stenosis have an
      excellent clinical prognosis. Nevertheless, there is a low risk of sudden death
      or rapid rate of progression to the symptomatic state. This low risk while
      patients remain asymptomatic does not outweigh the risk associated with valve
      replacement surgery or the complications of artificial prostheses, so surgery is
      not recommended for the entire group of asymptomatic patients. Therefore,
      therapeutic decisions in patients with aortic stenosis are based on the
      definition of symptomatic status and of hemodynamic severity, so accurate
      evaluation of these two issues is mandatory. However, establishing symptomatic
      status and severity of valve disease can be challenging because assessment of
      subjective symptoms and functional capacity is sometimes ambiguous, particularly
      in the elderly. Furthermore, it is well recognized that assessment of hemodynamic
      obstruction defined by echocardiographic indexes such as transvalvular pressure
      gradient and aortic valve area, is suboptimal because of technical difficulties
      and poor correlation with symptoms. Hence, aortic stenosis evaluation should be
      also performed introducing in clinical practice new simple indexes, such as
      function- and pressure-corrected indexes and energy loss index, that could
      provide a different estimate of disease severity, based on prognostic indication
      of adverse clinical outcome. Indeed, clinical outcome represents the real
      endpoint for defining severity and should be incorporated in clinical assessment
      and used to aid patient management in unclear situations. The development of
      heart failure in patients with aortic stenosis is associated with a high
      mortality rate and requires a careful management that includes an initial
      evaluation of the severity of the stenosis and the functional state of the left
      ventricle. Left ventricular dysfunction is usually due to afterload mismatch, but
      as end stage develops, decline in the intrinsic myocardial contractility becomes
      the most relevant mechanism. However, separating the effect of myocardial
      contractile dysfunction from that of afterload mismatch on pump performance is
      difficult. Dobutamine echocardiography can be useful both by testing myocardial
      contractile reserve and by separating true from relative aortic stenosis.
      Unfortunately the optimal management of patients with severe aortic stenosis and
      left ventricular dysfunction remains controversial, and we still have missing
      data to determine which patients are more likely to benefit from aortic valve
      replacement, by improving survival and functional status, with an acceptable
      perioperative mortality rate.

PMID- 15471151
TI  - [Statistical notes. Absolute and relative effect measures].
AB  - The aim of these statistical notes was to give the cardiologist the suitable
      tools for the understanding of the statistical aspects in the reading of papers
      presenting the results of randomized controlled clinical trials, in the most
      simple and intuitive way, without any previous knowledge of basic statistics. The
      fundamentals of the most common tools for the comparison of two experimental
      treatments, are developed by getting cue from classical cardiological examples
      and by guiding the reader, step by step, toward the understanding and critical
      discussion of the proposed examples. In particular, this note focuses the
      attention on the main "indicators" of absolute and relative effect measures by
      evidencing their most important differences.

PMID- 15471152
TI  - [How is syncope studied in the Italian hospitals?].
AB  - BACKGROUND: The aim of this study was to evaluate how the main tests for the
      diagnostic assessment of syncope are currently performed in the Italian
      hospitals. METHODS: During the early 2003 dedicated questionnaires were
      administered to about 400 Italian hospitals. About each test information was
      requested relative to: test protocol, laboratory equipment, patients evaluated
      during 2002. RESULTS: Eighty-four hospitals answered the questionnaire. A syncope
      dedicated ambulatory (at least once a week) was available during 2002 in 59/84
      hospitals, and 56 were dependent on the Cardiology Division. Carotid sinus
      massage was performed either in clinostatic and in orthostatic position in 60
      Centers and was repeated after atropine in 15. To define the test positivity, 35
      Centers followed the "symptom method". Only 15 Centers performed > 100 procedures
      during 2002 (range 3-500). Tilt testing was performed in 72 hospitals. A
      dedicated tilting bed was available in 65 Centers, continuous beat-to-beat
      pressure measurement in 22. Out of the 72 Centers, 55 followed the so-called
      "Italian protocol" as the main methodology of the test. Only 17 Centers performed
      > 100 procedures during 2002 (range 3-500). Adenosine test was performed in 26
      hospitals, the median dose of drug was 18 mg (range 6-20 mg); 25 out 26 Centers
      considered the test as positive when an asystolic pause > or = 6 s was observed.
      Only 6 Centers performed > 15 procedures during 2002 (range 1-204). An
      implantable loop recorder was available in 48 Centers. The number of implant
      procedures during 2002 varied among the Centers from 1 to 22. CONCLUSIONS: A
      great variability was observed concerning the methodology of each test and the
      number of procedures performed. Thus, a standardization effort about the
      methodology of syncope study is still needed by the medical associations.

PMID- 15471153
TI  - [Diabetes in Italy: a public health problem].
AB  - BACKGROUND: Type 2 diabetes is the most frequent form of diabetes in the adult
      population and is associated with an increasing risk of cardiovascular diseases.
      The objective of this study was to describe the prevalence and the state of
      control in an Italian population sample examined within the Osservatorio
      Epidemiologico Cardiovascolare study. METHODS: The sample of this study consisted
      in 8972 subjects, men and women aged 35-74 years. A fasting capillary blood
      glucose > or = 126 mg/dl or being on antidiabetic treatment were the criteria
      used to define diabetes, while a fasting capillary blood glucose < 140 mg/dl was
      considered to represent effective treatment (controlled diabetes) in treated
      patients. RESULTS: Diabetes was present in 8.4% of men and 6% in women. The
      prevalence of glucose intolerance was 8.2% in men and 4.3% in women. Only 50.7%
      of diabetic men and 56.5% of diabetic women knew about their disease; among these
      people, 21% was on treatment with oral antidiabetics and/or insulin. Such a
      therapy was effective in 39.5% of the treated cases. CONCLUSIONS: The prevalence
      of diabetes as well as glucose intolerance was greater in men and in the regions
      of the Center and South of Italy. The state of control of diabetes cannot be
      considered satisfactory; women and older age groups, when prevention strategies
      are less important, appear to be under better care.

PMID- 15471154
TI  - [Primary lymphoma of the right atrium: a case report].
AB  - Primary cardiac tumor is an extremely rare disease and is associated with a high
      mortality. The cases described in the literature are recently increased thanks to
      the employment of the new diagnostic methodologies (computed tomography, nuclear
      magnetic resonance, transesophageal echocardiography). Particularly the primitive
      lymphoma, non-HIV correlated, is very rare (< 1.5% of all cardiac tumors), but it
      is treatable when appropriately diagnosed. We report a case of 52-year-old
      patient who presented with an infiltrative mass in the right atrium. The
      examination of the tissue obtained by transvenous intracardiac biopsy with
      transesophageal echocardiography guidance revealed high grade non-Hodgkin's
      lymphoma of B-cell lineage. The patient achieved complete tumor remission after
      treatment with standard chemotherapy. This case demonstrates that early diagnosis
      might contribute to a better prognosis for patients with malignant lymphoma of
      the heart.

PMID- 15471155
TI  - [Usefulness of Doppler ultrasound in the diagnosis of renal artery stenosis in
      hypertensive children. Two case reports and review of the literature].
AB  - Renal artery stenosis, mainly due to fibromuscular dysplasia, is the second more
      common cause of arterial hypertension in children, after aortic coarctation. Two
      children sent to our Center of Pediatric Cardiology, one for arterial
      hypertension and the other for renal failure (associated with severe hypertension
      not previously recognized) are reported. In both of them the diagnosis of renal
      artery stenosis was established at Doppler ultrasonography, performed at the time
      of Doppler echocardiography. Both children were submitted to successful
      percutaneous transluminal angioplasty; short- and medium-term results are
      evaluated by Doppler ultrasonography. Renovascular disease is a potentially
      curable cause of renal artery stenosis in children. Renal artery evaluation by
      Doppler ultrasound is recommended in all hypertensive children who undergo
      Doppler echocardiography.

PMID- 15471156
TI  - [A strange neck pain].

PMID- 15471157
TI  - What can we learn from diagnostic tests that visualize the coronary arteries?
AB  - So far, no one procedure has proved more useful to the cardiovascular specialist
      than cardiac catheterization and coronary angiography. Coronary angiography is
      still alive and well and will remain so for many years.

PMID- 15471158
TI  - B-type natriuretic peptide measurement in heart failure.
AB  - Serum testing for the hormone B-type natriuretic peptide (BNP) may have clinical
      utility in congestive heart failure (CHF). This hormone is secreted predominantly
      by the left ventricular myocardium in patients with CHF. Measurement of serum BNP
      may improve diagnosis of CHF and may also help guide therapy in patients with
      CHF. The literature regarding the clinical utility of BNP measurement in CHF is
      reviewed.

PMID- 15471159
TI  - Concise review of atrial fibrillation: treatment update considerations in light
      of AFFIRM and RACE.
AB  - Atrial fibrillation (AF) is the most common clinically significant arrhythmia
      seen by clinicians. Prevalence is as high as 9.0% in patients aged > or = 80
      years, and incidence is projected to be more than 5.6 million patients in the
      U.S. by 2050. Recently, new trials have challenged the traditional belief that
      rhythm control is inherently superior to rate control in these patients. This
      article reviews the basic tenets of treatment for AF and discusses how new trial
      data integrate into these protocols. A concise treatment algorithm is provided
      and new and upcoming more aggressive interventional treatment options are
      discussed. This review is designed to help the general practitioner decide how to
      treat patients in the outpatient setting, evaluate which patients should be
      hospitalized for management, and which patients should be referred to a
      cardiologist.

PMID- 15471161
TI  - Images in cardiology: Pericardial cyst.

PMID- 15471160
TI  - A systolic murmur is a common presentation of aortic regurgitation detected by
      echocardiography.
AB  - BACKGROUND: The finding of aortic regurgitation at a classical examination is a
      diastolic murmur. HYPOTHESIS: Aortic regurgitation is more likely to be
      associated with a systolic than with a diastolic murmur during routine screening
      by a noncardiologist physician. METHODS: In all, 243 asymptomatic patients (mean
      age 42 +/- 10 years) with no known cardiac disease but at risk for aortic valve
      disease due to prior mediastinal irradiation (> or = 35 Gy) underwent
      auscultation by a noncardiologist followed by echocardiography. A systolic murmur
      was considered benign if it was grade < or = II/VI, not holosystolic, was not
      heard at the apex, did not radiate to the carotids, and was not associated with a
      diastolic murmur. RESULTS: Of the patients included, 122 (49%) were male, and 86
      (35%) had aortic regurgitation, which was trace in 20 (8%), mild in 52 (21%), and
      moderate in 14 (6%). A systolic murmur was common in patients with aortic
      regurgitation, occurring in 12 (86%) with moderate, 26 (50%) with mild, 6 (30%)
      with trace, and 27 (17%) with no aortic regurgitation (p < 0.0001). The systolic
      murmurs were classified as benign in 21 (78%) patients with mild and 8 (67%) with
      moderate aortic regurgitation. Diastolic murmurs were rare, occurring in two
      (14%) with moderate, two (4%) with mild, and three (2%) with no aortic
      regurgitation (p=0.15). CONCLUSIONS: An isolated systolic murmur is a common
      auscultatory finding by a noncardiologist in patients with moderate or milder
      aortic regurgitation. A systolic murmur in patients at risk for aortic valve
      disease should prompt a more thorough physical examination for aortic
      regurgitation.

PMID- 15471162
TI  - Closure of defects of the atrial septum in adults using the Amplatzer device: 100
      consecutive patients in a single center.
AB  - BACKGROUND: Transcatheter device closure of atrial septal defects (ASD) is an
      alternative to surgery, but experience is limited in adults, especially in those
      with large (> 26 mm) defects. HYPOTHESIS: We investigated the safety, efficacy,
      and learning curve for closure of ASD and patent foramen ovale (PFO) using the
      Amplatzer device. METHODS: In all, 101 procedures were carried out in 100
      consecutive adult patients in a single cardiac center between July 1998 and
      August 2002. RESULTS: Preprocedure diagnosis was ASD and PFO in 50 patients each.
      A device was deployed in 94 of 101 attempts (93%) in 94 of 100 patients (94%).
      Atrial septal defect device sizes were 10-38 mm, median 24 mm, and 40% were > 26
      mm. Major complications occurred in 2 of 100 patients (2%). One ASD device
      displaced requiring surgery within 24 h and one patient with PFO experienced
      pericardial tamponade; there were no deaths. Local vascular complications
      occurred in 4 of 100 (4%) and late complications in 4 of 100 (4%) patients.
      Patent foramen ovale closure was quicker (p<0.001), required less radiation
      (p=0.04), and was associated with fewer local vascular complications than ASD
      closure (p=0.04). Deployment of ASD devices > 26 mm was not associated with
      increased complications, length of procedure, or radiation compared with devices
      < or = 26 mm (all p>0.05). Complications in the first 35 patients were more
      frequent than in subsequent patients: 7 of 35 (20%) versus 3 of 65 (4.6%)
      (p=0.04); procedure and fluoroscopy times (both p<0.001) and radiation doses
      (p=0.001) were also higher. CONCLUSION: The Amplatzer device is an effective
      method for transcatheter closure of interatrial defects in adults, including
      large ASDs up to 38 mm. Major complications are uncommon. A learning curve of
      approximately 35 cases was suggested by the decline of complications, procedure
      times, and radiation exposure.

PMID- 15471163
TI  - Images in cardiology: Heparin-induced thrombocytopenia and thrombosis.

PMID- 15471164
TI  - Persistent left superior vena cava draining into the coronary sinus: report of 10
      cases and literature review.
AB  - BACKGROUND: Persistent left superior vena cava (PLSVC) is the most common
      thoracic venous anomaly. HYPOTHESIS: This study examines the epidemiologic,
      clinical, and morphologic characteristics of a cohort of patients with PLSVC
      draining into the coronary sinus. METHODS: We examined the clinical and
      morphologic characteristics of patients with PLSVC draining into the coronary
      sinus diagnosed at a single referral hospital for a defined population in
      northwestern Spain. We designed a prospective study of the case records of all
      patients diagnosed with PLSVC draining into the coronary sinus at the
      echocardiography laboratory of the Hospital Xeral-Calde from January 2001 through
      December 2002. Patients were included if they had a PLSVC diagnosed by
      transthoracic echocardiogram (TTE) using an echo-contrast enhancement and
      confirmed by a magnetic resonance (MR) imaging. Ten patients (6 women) fulfilled
      the inclusion criteria described above. All patients were adults and had
      associated heart disease, including a congenital heart disease in three cases.
      RESULTS: Magnetic resonance imaging examination confirmed the presence of PLSVC
      and the site of drainage into the coronary sinus. Absence of the right superior
      vena cava was observed only in three patients, in whom the main coronary sinus
      size was significantly increased. Absence of the left brachiocephalic vein was
      diagnosed in five patients. CONCLUSION: This study describes 10 new cases of
      PLSVC and supports the necessity of considering PLSVC draining into the coronary
      sinus in the diagnosis of patients presenting with dilated coronary sinus
      diagnosed by TTE. It also underlines the important role of MR imaging in the
      evaluation of these abnormalities. An associated heart disease must always be
      excluded in these patients.

PMID- 15471165
TI  - Does mild pulmonary stenosis progress during childhood? A study of its natural
      course.
AB  - BACKGROUND: Increase in the gradient in congenital pulmonary valvular stenosis
      during follow-up is a subject of controversy and could determine the need for
      treatment in pediatric patients. HYPOTHESIS: It is postulated that a gradient <50
      mmHg shows a stable or decreasing tendency at follow-up for congenital pulmonary
      valvular stenosis. METHODS: Thirty-five patients with pulmonary stenosis,
      isolated and not treated, were followed for 7 years (interquartilic rank 5.7
      years) at 1.5-year intervals. Clinical and complementary tests
      (electrocardiogram, x-ray, Doppler echocardiogram) were undertaken. The gradient
      was measured by Doppler and by using the clinical formula derived from the New
      England Study (Ellison). The changes observed from the initial to the final
      consultation were analyzed by means of the Student's t-test, paired Wilcoxon, and
      Pearson correlation coefficient. RESULTS: No significant changes were noted on
      symptoms or physical examination. Signs of cardiac enlargement diminished on both
      ECG (R wave in V1, p<0.0001) and x-ray (cardiothoracic ratio, p<0.0007), with a
      decreasing gradient trend during the follow-up period (p<0.026) as well.
      CONCLUSIONS: The gradient trend confirms the stable nature of mild pulmonary
      stenosis. In our study, we found that patients aged >6 months, whose gradients
      were below 40 mmHg at the time of diagnosis, remained stable and required no
      treatment. Furthermore, the follow-up control and clinical management of these
      patients may then be performed at intervals of 2 years or more.

PMID- 15471166
TI  - Effects of cyclooxygenase inhibition on endothelial function in hypertensive
      patients treated with angiotensin-converting enzyme inhibitors.
AB  - BACKGROUND: Cyclooxygenase inhibition restores endothelium-dependent
      vasodilatation in hypertension, but it is unknown whether it restores endothelial
      function in hypertensive patients treated with angiotensin-converting enzyme
      (ACE) inhibitors. HYPOTHESIS: The purpose of the present study was to evaluate
      the effects of cyclooxygenase inhibition on endothelial function in hypertensive
      patients treated with ACE inhibitors. METHODS: Endothelium-dependent flow
      mediated dilatation (FMD) and endothelium-independent glyceryl trinitrate-induced
      dilatation were investigated in 10 patients treated with enalapril (ACE group),
      11 patients treated with manidipine and metoprolol (non-ACE group), and 12
      normotensive control subjects. After administration of 1000 mg of aspirin, FMD
      was investigated once again. Plasma cyclic guanosine monophosphate (cGMP) and
      eicosanoids were also measured during reactive hyperemia before and after aspirin
      administration. RESULTS: Flow-mediated dilatation was more impaired in the non
      ACE group than in the ACE group (8.3 +/- 3.8%, 5.7 +/- 1.7%, respectively,
      p<0.04). Glyceryl trinitrate-induced dilatation was similar in the ACE group, the
      non-ACE group, and in the control subjects. In the ACE group, FMD was reduced
      after administration of aspirin (5.3 +/- 4.2%, p<0.05). The percent change in FMD
      after administration of aspirin correlated significantly with percent change in
      cGMP (r=0.77, p<0.03; y-intercept, -62.1%, p<0.01). After aspirin administration,
      levels of thromboxane B2 and 6-keto-prostaglandin(1alpha) were significantly
      decreased compared with those before aspirin administration in all groups.
      CONCLUSIONS: Cyclooxygenase inhibition may reduce the beneficial effect on
      endothelium-dependent vasodilatation induced by ACE inhibitors. The results
      suggested that prostacyclin in addition to nitric oxide plays a significant role
      in the restoration of endothelial function in hypertensive patients treated with
      ACE inhibitors.

PMID- 15471167
TI  - Left atrial systolic function in primary and familial amyloidosis: assessment
      from left atrial volume change.
AB  - The severity of left ventricular involvement may differ between primary (PA) and
      familial amyloidosis (FA). This study examined whether differences in left atrial
      (LA) systolic function are also present. Twenty-eight patients (18 men, 10 women,
      aged 59 +/- 12 years) with PA, 17 (11 men, 6 women, aged 40 +/- 11 years) with
      FA, and 25 normal controls (18 men, 7 women, aged 56 +/- 14 years) underwent
      transthoracic M-mode, two-dimensional, and Doppler echocardiography. Left atrial
      volumes were determined at mitral valve (MV) opening (maximal, Vmax),
      electrocardiographic P wave (onset of atrial systole, Vp), and MV closure
      (minimal, Vmin) from the apical two-and four-chamber views using the biplane area
      length method. Left atrial systolic function was assessed with the LA active
      emptying volume (ACTEV) = Vp-Vmin and fraction (ACTEF) = ACTEV/Vp. The E/A ratio
      was increased (1.34 +/- 0.93 vs. 0.89 +/- 0.3), whereas deceleration time was
      decreased (168.1 +/- 33.7 vs. 196.2 +/- 34.2 ms) in PA compared with FA (p<0.05).
      Vmax and Vp were similar in PA and FA and greater than in the controls (46.6 +/-
      14 vs. 40 +/- 11.4 vs. 27.1 +/- 6.3 cm3/m2, p<0.01, and 33.4 +/- 11.6 vs. 29.7 +/
      10.8 vs. 16.8 +/- 3.8 cm3/m2, p<0.01, respectively). The ACTEV was lower in PA
      and in the controls than in FA (6.7 +/- 2 vs. 6.2 +/- 2.2 vs. 8.5 +/- 3.3,
      respectively, p<0.05). The ACTEF was lower in PA than in FA and both were lower
      than those in the controls (20 +/- 5% vs. 28 +/- 7% vs. 36 +/- 11%, respectively,
      p<0.01). Despite a similar increase in LA volume, LA systolic dysfunction is more
      pronounced in PA than in FA. This is most likely due to the restrictive left
      ventricular physiology possibly associated with depressed LA contractility in the
      former.

PMID- 15471168
TI  - Obesity is not only an adult problem. C. R. Conti: Clin Cardiol 2004;27:183-184.

PMID- 15471169
TI  - Profile in Cardiology. David H. Spodick.

PMID- 15471170
TI  - The WVSMA: continuing to go for the gold.

PMID- 15471171
TI  - Physician supply in key medical specialties in West Virginia hospitals, 2001
      2004.
AB  - This article describes the development, implementation and analysis of an ongoing
      prospective physician supply survey of the largest acute care hospitals in West
      Virginia. This survey was designed to assess changes in availability of
      physicians in key specialties from 2001-2004, a period of years that included a
      "malpractice insurance crisis." The malpractice crisis in this article describes
      the period of time in 2001-2002 when medical malpractice insurance rates
      increased abruptly in West Virginia and a number of physicians publicized their
      departure from practice in the state. We calculated the absolute and relative
      percentage change in the median number of physicians in each specialty between
      2001-2004, calculated percentage change for each specialty by year, and performed
      univariate analysis on the percentage changes among all hospitals. We also
      calculated univariate analysis on the percentage changes among all hospitals. The
      median number of staff physicians in these hospitals declined steadily from 2001
      2004. Declines in the number of specialists (some statistically significant)
      occurred, especially early in the three-year period, notably among surgical
      specialties. The availability of nephrologists increased significantly from 2003
      2004. Decreases in staff physician numbers may have leveled off, but there is no
      evidence of sustained growth.

PMID- 15471172
TI  - Serum TSH variability in normal individuals: the influence of time of sample
      collection.
AB  - Difficulty in treatment decisions can arise when TSH levels measured on the same
      patient on the same day but at different times show considerable variability.
      This study was a prospective, observational evaluation of 100 consecutive adult
      patients who had serum TSH tests ordered by attending physicians at an outpatient
      clinic. Early morning fasting serum TSH levels were compared to late morning non
      fasting serum TSH levels in the same patients on the same day The late morning
      non-fasting TSH tests declined in 97 of 100 subjects by an average of 26.39% when
      compared to early morning, fasting, TSH test results. This lead to
      reclassification of 6% of patients from presumptive subclinical hypothyroidism to
      "normal." Since the time of day of phlebotomy or the fasting or non-fasting
      status of the patient, or both, can significantly affect serum TSH test results,
      the diagnosis of subclinical hypothyroidism should not be made only on a fasting
      TSH measurement. Further studies are needed to determine the independent effects
      of the time of phlebotomy and fasting/non-fasting status on TSH levels.

PMID- 15471173
TI  - A brief summary of alcohol intervention research at West Virginia University from
      1998-2003.
AB  - Injury resulting in death and disability and alcohol-related problems are two
      major problems in West Virginia, yet few effective preventive strategies are
      available. A relatively simple and effective preventive strategy, appropriate for
      all health care providers, can help to alter excessive alcohol consumption and
      its resulting harm and consequences. Over the past five years, a series of
      alcohol intervention projects have been conducted in the Emergency Department at
      West Virginia University Hospital and other medical settings. Short motivational
      counseling sessions, which are referred to as screening and brief intervention
      (SBI), were tailored to each patient's needs. SBI is a secondary prevention
      strategy used to help persons identified with alcohol problems to decrease their
      drinking and reduce the harm caused by alcohol. To date, 90% of the nearly 8,000
      eligible patients have consented to participate in these studies. Follow-up rates
      have ranged between 45% and 61%. This article describes the methodologies and
      results of our SBI studies and their relevance to West Virginia health care
      providers.

PMID- 15471174
TI  - Methadone-induced torsade de pointes in a patient with normal baseline QT
      interval.
AB  - Torsade de pointes (TdP) is a life threatening cardiac arrhythmia that is
      typically associated with prolongation of the QT interval. A wide variety of
      nonantiarrthymic medications may trigger TdP in patients with prolonged QT
      interval, only a few reports have described an association between TdP and
      methadone. We report a case of TdP caused by a large dose of methadone in a
      patient with presumably normal QT interval at baseline prior to his presentation
      at the hospital.

PMID- 15471175
TI  - Concern about mad cow disease: end of the beginning, or beginning of the end?

PMID- 15471176
TI  - Treatment of chronic hepatitis C patients not responding to combination therapy
      with ribavirin and interferon alpha--hype or hope?

PMID- 15471178
TI  - Massive subcutaneous bleeding as a first manifestation of chronic myeloid
      leukemia in chronic phase.

PMID- 15471177
TI  - [Dietary fibre: more than a matter of dietetics. II. Preventative and therapeutic
      uses].
AB  - A nutrition rich in fibre has a preventive effect against constipation, colon
      diverticulosis, carcinoma of the large bowel and stomach, type 2-diabetes,
      metabolic syndrome and cardiovascular disease. In case of constipation,
      diverticulosis and diabetes this effect solely depends on dietary fibre.
      Regarding carcinomas and cardiovascular diseases, so far unknown factors
      integrated in or associated with fibre-rich food may also contribute to the
      preventive effect. Therapy with dietary fibre is indicated for constipation,
      colon diverticulosis, diarrhea, diabetes, and hypercholesterinemia. The
      individual dietary fibres differ substance-specifically. Food-integrated dietary
      fibre such as whole-grain bread, vegetables and fruit have their place in
      prevention. Dietary fibre preparations such as wheat bran, flax seed or sugar
      beet fibre are useful in the treatment of constipation, colon diverticulosis and
      adiposity. Oat bran is preferentially used in hypercholesterinemia. Purified
      dietary fibres such as cellulose, guar, psyllium, and beta-glucan have an anti
      diabetic, all viscous fibres an anti-lipaemic effect. The therapeutic dosages of
      dietary fibre preparations are 20-40 g/day and of purified fibres substances 10
      20 g/day respectively.

PMID- 15471179
TI  - Creutzfeldt-Jakob disease in Slovenia from 1985 to 2003.
AB  - AIM: The epidemic of bovine spongiform encephalopathy and subsequent emergence of
      a new variant of Creutzfeldt-Jakob disease have raised great public concern,
      initiating improved and prospective surveillance of human prion diseases in
      Europe and all over the world. This report briefly presents the epidemiology,
      clinical data, neuropathology, immunohistochemistry, biochemistry, and prion
      protein gene analysis of Slovenian cases of Creutzfeldt-Jakob disease from
      January 1985 to the end of 2003. MATERIALS, METHODS AND RESULTS: During the 19
      year period, 39 suspected cases of Creutzfeldt-Jakob disease were referred and 22
      were confirmed. The prion-protein gene was analyzed in 12 of the confirmed cases
      and the protein glycosylation pattern in 11. There was a low average incidence of
      Creutzfeldt-Jakob disease (0.5/million) throughout the surveillance period, but a
      pronounced increase between January 2001 and December 2003 (to 1.9/million/year).
      A high female to male ratio (2.5/1) was noted. All of the confirmed cases were
      defined as sporadic Creutzfeldt-Jakob disease based on the clinical data,
      neuropathological findings, glycosylation pattern, and gene analysis. All tested
      cases had a type-2 glycosylation pattern; eleven of the twelve tested patients
      were homozygous at codon 129 of the prion-protein gene (1 VV and 10 MM) and one
      was heterozygous. CONCLUSION: The small number of Slovenian cases of sporadic
      Creutzfeldt-Jakob disease during the last 19 years has shown a pronounced
      increase in incidence, reflecting improved surveillance, and a high female to
      male ratio, where female cases are more than twice as numerous as male cases.

PMID- 15471181
TI  - Extracorporeal shockwave treatment is effective in calcific tendonitis of the
      shoulder. A randomized controlled trial.
AB  - BACKGROUND: Calcific tendonitis of the shoulder is often associated with chronic
      pain and impairment of function. Extracorporeal shockwave therapy (ESWT) is
      considered to be a treatment option. We compared the effects of two different
      ESWT regimens. METHODS: 43 patients (57 shoulders) with symptomatic calcific
      tendonitis of the shoulder for more than six months were included in a double
      blinded study. Thirty-one shoulders were treated at the area of maximum pain with
      application of 2 x 2000 impulses of 0.28 mJ/mm2 at an interval of two weeks
      (treatment group) and 26 shoulders with 2 x 2000 impulses of < 0.07 mJ/mm2 at an
      interval of two weeks (control group), without pretreatment analgesia. Shoulder
      function (Constant score) and pain (visual analogue scale, VAS) were assessed
      before treatment and at one week, three months and seven months after treatment.
      Shoulder X-rays were performed at the 3- and 7-month follow-up visits. RESULTS:
      Improvement in Constant score was significantly higher in the treatment group at
      all follow-up visits (p < 0.05). Seven months post-treatment, calcifications
      dissolved completely in 19% of the treatment group and 8% of the control group,
      and a > 50% reduction was observed in 19% and 8% respectively. With regard to
      reduction of pain, there was significant improvement in the treatment group
      compared with the control group at the 1-week follow-up (p < 0.05). However, at
      the 3-month and 7-month visits, no significant between-group difference in pain
      could be detected. CONCLUSION: As applied, ESWT with an energy flux density of
      0.28 mJ/mm2 led to a significantly greater improvement in shoulder function and a
      slightly higher, nonsignificant, rate of > 50% disintegration of calcific
      deposits compared with the control group. However, this did not result in
      reduction of pain.

PMID- 15471180
TI  - Retreatment of patients with chronic hepatitis C not responding to
      interferon/ribavirin combination therapy with daily interferon plus ribavirin
      plus amantadine.
AB  - There is currently no accepted therapeutic regimen for patients with chronic
      hepatitis C who failed to respond to standard combination treatment with
      interferon-alpha plus ribavirin. We investigated triple combination treatment
      with induction dosing of interferon-alpha plus ribavirin plus amantadine in these
      difficult-to-treat patients. Nonresponders (n = 67), breakthroughs (n = 16) and
      relapsers (n = 19) to previous interferon/ribavirin combination treatment of at
      least 6 months were included. For the first 16 weeks, patients received
      interferon-alpha2a 6 MU daily, ribavirin 800-1200 mg/d, and amantadine 200 mg/d.
      In cases of undetectable HCV RNA at week 12, treatment was continued with
      interferon-alpha2a 6 MU every other day and the same doses of ribavirin and
      amantadine until week 48. In cases of HCV RNA positivity at week 12, treatment
      was stopped. A total of 102 patients were enrolled (80%: genotype 1, 19%:
      cirrhosis). HCV RNA was negative in 35/102 patients (34%) at week 12 and in 27/
      102 patients (26%) at the end of treatment. Virological response was sustained in
      15/102 patients (15%). On-treatment virological response was higher in previous
      relapsers/breakthroughs than in previous nonresponders (week 12: 49% vs. 27%, p <
      0.05; week 48: 46% vs. 16%, p < 0.01) but no such difference was found for
      sustained virological response (20% vs. 12%, NS). In conclusion, triple
      combination treatment with daily interferon-alpha plus ribavirin plus amantadine
      for 3 months can induce virological response in a considerable number of
      nonresponders/relapsers to previous dual combination treatment, but the sustained
      virological response rate remains low.

PMID- 15471182
TI  - [Is it possible to reduce CMV-infections after heart transplantation with a three
      month antiviral prophylaxis? 7 years experience with ganciclovir].
AB  - BACKGROUND: In the early phase after heart transplantation (HTX) patients are at
      high risk for infection because of intensified immunosuppression. This
      retrospective study evaluates the efficacy of a three-month antiviral
      cytomegalovirus (CMV) prophylaxis. PATIENTS AND METHODS: 133 patients received a
      three-month combined intravenous and oral CMV prophylaxis with Ganciclovir
      (Cymevene after HTX between 1997 and April 2003 (group II). They were compared to
      a historical group consisting of 40 patients, who had undergone HTX between 1995
      and 1996 (group I; CMV-prophylaxis: hyperimmune globuline (Cytotect) for the
      first post-operative month in combination with orally administered aciclovir
      (Zovirax) for 6 months). Demographic data of organ recipients and donors in both
      groups were comparable, except for underlying cardiac diseases (p = 0.016). All
      patients had identical postoperative immunosuppressive regimes. RESULTS: Group II
      had a significantly lower mortality rate (GI: 37.5%, GII: 9.8%; p < 0.001); one
      year survival (p = 0.001) and overall survival (p = 0.001) were significantly
      better than in group I. Patients of group II had fewer rejection episodes > or =
      grade II ISHLT requiring treatment (p < 0.001). Group II presented significantly
      fewer positive CMV blood samples (p = 0.005) and CMV infections (26% versus 47,5%
      in GI; p = 0.008), and a later onset of infections after HTX than group I (group
      I with a mean interval of 5.8 weeks after HTX, group II: 24.8 weeks after HTX; p
      < 0.001). CONCLUSION: Incidence of CMV infection was significantly lowered under
      ganciclovir prophylaxis, infections occurred at a later time point after HTX,
      when patients were immunologically more competent. The proportion of higher grade
      rejection episodes was markedly reduced and survival was improved.

PMID- 15471183
TI  - [Diagnosis and therapy of restless legs syndrome in the doctor's office].
AB  - BACKGROUND: Restless legs syndrome (RLS) is a movement and sleep disorder with
      leg dysesthesias with a high prevalence (9-18% in Austria). AIM OF THE STUDY:
      Determination of frequency, diagnosis and therapy of RLS in general practitioner
      and specialist offices. METHODS: Telephone survey of a random sample of 120
      general practitioners, 100 neurologists and 80 specialists in internal medicine.
      RESULTS: 69% of the whole sample of doctors reported seeing 1 to 10 RLS patients,
      but in proportion to the prevalence of these two conditions fewer cases of RLS
      than of Parkinson's disease are treated. In all three groups of doctors, 84%
      consider the 4 key symptoms (urge to move the legs accompanied or caused by
      dysesthesia; worsening of symptoms at rest or inactivity; relief by activity;
      worsening of symptoms in the evening/at night) the most important diagnostic
      criteria for RLS, followed by a complaint of disturbed sleep (75%), daytime
      tiredness (43%) and dopaminergic responsiveness in a therapeutic trial (29%). 83%
      of general practitioners and 86% of medical specialists refer their RLS patients
      to a neurologist, 19% to a polysomnographic examination. 75% of doctors decide
      for pharmacological treatment of RLS, 18% for psychotherapy, 15% for household
      remedies. 54% of all doctors (70% of the neurologists, 68% of the GPs, 48% of the
      medical specialists) prescribe dopamine agonists. L-Dopa is used by 49% (61% of
      the neurologists, 42% of the GPs, 44% of the medical specialists). 17% prescribe
      GABAergic drugs, 6% opiates. 51% would be highly interested in obtaining a drug
      specifically registered for the treatment of RLS. CONCLUSION: RLS is not as well
      known as Parkinson's disease. Thus providing doctors with relevant information
      and further education programs on this subject seems desirable. In Austrian
      doctors' offices the diagnosis of RLS is usually obtained clinically on the basis
      of the 4 key symptoms. Patients suffering from insomnia of multifactorial
      pathogenesis should be referred to an outpatient clinic for sleep disorders with
      an associated sleep laboratory. Especially neurologists and GPs consider dopamine
      agonists the treatment of first choice, closely followed by L-Dopa.

PMID- 15471184
TI  - Highly refractory acute myeloid leukemia.
AB  - In this study we evaluated 103 patients suffering from acute myeloid leukemia
      (AML) who did not respond to induction chemotherapy and defined a sub-group of
      patients with highly refractory disease characterized by a persistence of more
      than 1 G/L blast cells in the peripheral blood between days 12 and 16 of the
      first induction cycle. Only seven patients (one female, six males) met these
      criteria. Their median age was 65 years (range 41-82 years). Four had de novo AML
      and three secondary AML. Cytogenetic analysis was performed in six patients:
      complex aberrations were detected in four patients and, unexpectedly, normal
      karyotypes were found in the other two. Analysis of multidrug-resistance factors
      revealed high co-expression of P-glycoprotein (P-gp) and lung resistance protein
      (LRP) in all four patients with highly refractory disease tested a finding in
      only 6% of patients with refractory disease and 3% of patients who achieved
      complete remission (CR) of disease. Furthermore, patients with highly refractory
      AML had substantially higher leukocyte counts than patients with refractory AML
      or CR, although this was not significant statistically. Overall, patients with
      highly refractory AML are characterized by a high incidence of complex
      cytogenetic aberrations and marked expression of drug transporters.

PMID- 15471185
TI  - Spontaneous bilateral diaphragmatic paralysis: a rare cause of respiratory
      failure.
AB  - Bilateral diaphragmatic paralysis (BDP) can occur in the course of motor neuron
      disease, myopathy, or from mechanical damage or the use of "ice slush" during
      cardiac surgery. BDP has been observed during and after infections, associated
      with systemic lupus erythematosus and mediastinal tumors, or may have idiopathic
      etiology. It is a serious and life-threatening condition. A 62-yr-old man
      presented with slowly progressive dyspnoea that worsened in the supine position
      and on bending forward. Chest X-rays, fluoroscopy, lung-function parameters and
      blood-gas analysis revealed respiratory failure. BDP was confirmed from a phrenic
      nerve stimulation test and measurement of transdiaphragmatic pressure (Pdi).
      Since there was no evidence of an obvious etiology, BDP was considered
      idiopathic. Other muscles were not involved. The pathological basis was probably
      focal demyelination in segments of the phrenic nerve. Because of increasing
      diaphragmatic muscle fatigue, the patient was treated with a nasal mask providing
      bi-level positive airway pressure (BiPAP) ventilation during the night. Clinical
      suspicion of BDP should always be raised in patients suffering slowly progressive
      dyspnoea without any obvious cardiac, metabolic or traumatic predisposing
      factors, and orthopnoea and dyspnoea on bending forward. Electromyographic tests
      and measurement of Pdi can reveal the correct diagnosis.

PMID- 15471187
TI  - Cervical disease screening and detection: emerging techniques in molecular
      diagnostic assays.

PMID- 15471186
TI  - [Medical aspects of objectifying torture sequels].
AB  - Migration, civil wars and other conflicts in various regions of the world have
      led to a drastic increase in the number of displaced persons and refugees.
      Associated with this development is an increase in the number of torture victims
      seeking asylum. This means that the medical personnel is increasingly confronted
      with the evaluation and therapy of torture victims. The methods of verification
      of sequels of torture are of utmost importance in the work-up of treatment
      centres for survivors of torture. Since each organ can be affected by torture, a
      multidisciplinary cooperation is mandatory for the examination of torture
      victims. In this paper we shall discuss some aspects concerning the diagnosis of
      injuries caused by torture which are essential for interviewing and examining
      torture victims in order to objectify sequels of torture.

PMID- 15471188
TI  - Cytology information system helps improve patient care.

PMID- 15471189
TI  - A chat with the good doctor: how can the lab support the physician in the allergy
      march?

PMID- 15471190
TI  - Part I: Tumor markers from A to Z.

PMID- 15471191
TI  - Building bridges one bar code at a time: laboratorians and nurses pursue patient
      ID system.

PMID- 15471192
TI  - ABX VP Jim Williams affirms perpetual growth mode.

PMID- 15471193
TI  - Addressing workplace issues.

PMID- 15471194
TI  - Legal dangers of testing unacceptable specimens.

PMID- 15471195
TI  - Specialty histology labs increase risks.

PMID- 15471196
TI  - Intermediate- to high-risk prostate cancer patient treated with radiation
      therapy.

PMID- 15471198
TI  - Clinical trials referral resource. Current clinical trials investigating
      Triapine.

PMID- 15471197
TI  - Trastuzumab in breast cancer.
AB  - Trastuzumab (Herceptin) is a therapeutic monoclonal antibody specific for the
      human epidermal growth factor receptor type 2 (HER2), a cell-surface tyrosine
      kinase receptor overexpressed by 25% to 30% of breast cancers. The drug is now
      regarded as one option for standard therapy in HER2-overexpressing metastatic
      breast cancers. It is associated with a moderate response rate as a single agent,
      and in combination with standard chemotherapy, can produce greater response rates
      and prolong the survival of women with advanced breast cancer. Its activity in
      metastatic breast cancer has led to active clinical trials examining its
      potential role in the neoadjuvant and adjuvant settings. The successful clinical
      development of trastuzumab provides further proof of principle that biologically
      targeted therapies can have a profound impact on the management of breast cancer.
      Here we review the clinical development of this novel agent, emphasizing the
      potential for therapeutic synergy when trastuzumab is combined with both standard
      chemotherapy and innovative molecularly targeted and biologic agents.

PMID- 15471199
TI  - Bevacizumab proves active in wide range of cancers.

PMID- 15471200
TI  - Coming to grips with hand-foot syndrome. Insights from clinical trials evaluating
      capecitabine.
AB  - Hand-foot syndrome is a localized cutaneous side effect associated with the
      administration of several chemotherapeutic agents, including the
      oralfluoropyrimidine capecitabine (Xeloda). It is never life-threatening but can
      develop into a painful and debilitating condition that interferes with patients'
      normal daily activities and quality of life. Several symptomatic/prophylactic
      treatments have been used to alleviate hand-foot syndrome, but as yet there is
      insufficient prospective clinical evidence to support their use. The only proven
      method of managing hand-foot syndrome is treatment modification (interruption
      and/or dose reduction), and this strategy is recommended for patients receiving
      capecitabine. Retrospective analysis of safety data from two large phase III
      trials investigating capecitabine as first-line therapy in patients with
      colorectal cancer confirms that this strategy is effective in the management of
      hand-foot syndrome and does not impair the efficacy of capecitabine. This finding
      is supported by studies evaluating capecitabine in metastatic breast cancer.
      Notably, the incidence and management of hand-foot syndrome are similar when
      capecitabine is administered in the metastatic and adjuvant settings, as
      monotherapy, or in combination with docetaxel (Taxotere). It is important that
      patients learn to recognize the symptoms of hand-foot syndrome, so that prompt
      symptomatic treatment and treatment modification strategies can be implemented.

PMID- 15471201
TI  - Melanoma in the older person.
AB  - Melanoma accounts for the majority of skin cancer deaths worldwide and has
      dramatically increased in incidence over the past half-century. Despite recent
      trends showing improved survival, and stabilization of incidence rates in younger
      Americans, melanoma incidence and mortality continue to rise unabated in older
      individuals, particularly in men over age 65. Efforts at early clinical detection
      of melanoma in older individuals should take into account the differences in
      melanoma subtypes in older individuals, potentially reduced access to medical
      specialists in this population, as well as comorbidities that may affect ability
      to undergo treatment for advanced disease. Secondary melanoma prevention should
      be focused on targeted education to older men and their spouses for early
      detection and reduction of mortality in this extremely high-risk group.

PMID- 15471202
TI  - Bortezomib data show improved survival in patients with relapsed multiple
      myeloma.

PMID- 15471203
TI  - Herceptin produces clinical benefit in metastatic breast cancer regardless of
      tumor response.

PMID- 15471204
TI  - Sutter Health expands EMR system to capitated physicians.

PMID- 15471205
TI  - Sutter Connect beefs up back-office functions.
AB  - Sutter Connect, an administrative services organization, uses a variety of
      information technology methods to reduce PMPM costs. Find out what back office
      functions are used to manage more than dollars 504 million in capitation dollars
      for about 415,000 commercial and Medicare Advantage managed care lives.

PMID- 15471206
TI  - Capped organizations gain edge with care management, incentives.
AB  - California medical groups and IPAs are more likely than physician organizations
      in other states to use recommended care management processes for treating
      patients with chronic illnesses primarily because they have a greater number of
      external incentives to improve quality.

PMID- 15471207
TI  - Capitated providers, health plans cut costs.
AB  - Capitated physician organizations and health plans are using case management
      approaches to reduce PMPM costs in patients with chronic conditions like
      diabetes, asthma, congestive heart failure and hypertension. Read about their
      ongoing efforts to address chronic disease, which accounts for up to 80% of total
      health care expenditures.

PMID- 15471208
TI  - Potential and challenges of a human cytome project.
AB  - BACKGROUND: The elucidation of the molecular pathways from the 20-40.000 genes of
      the sequenced human genome via investigation of genetic networks and molecular
      pathways up to the cellular and organismal phenotypes is highly complex and time
      consuming. STRATEGY AND GOALS: The proposed upside-down research strategy of a
      human cytome project accesses the expressed molecular cell phenotypes by
      differential screening, for example of diseased versus healthy, or
      undifferentiated versus differentiated cells to obtain information on disease or
      differentiation related molecular hotspots at the single cell level. The genome
      serves as inventory of the biomolecular capacities of organisms while the
      mechanisms of genome realisation are initially entirely bypassed. Detected
      molecular hotspots are further investigated by backward directed systems biology,
      including molecular pathway modelling to elucidate disease related molecular
      pathways. New drug targets may be identified to specifically influence such
      pathways. Differential screening provides, in addition, individualized disease
      course predictions for everyday medicine, in form of "predictive medicine by
      cytomics." The early recognition of future disease complications enables an
      immediate application of preventive therapies. This is likely to lower disease
      related irreversible tissue destruction and adverse drug reactions and will allow
      to individually optimize patient therapy. OUTLOOK: Immediate medical use,
      facilitated access to the detection of new drug targets, increased research speed
      and the stimulation for advanced technological developments represent major
      driving forces for the efforts to establish a human cytome project.

PMID- 15471209
TI  - New technologies for the human cytome project.
AB  - Cytomes or cell systems are composed of various kinds of single-cells and
      constitute the elementary building units of organs and organisms. Their
      individualised (cytomic) analysis overcomes the problem of averaged results from
      cell and tissue homogenates where molecular changes in low frequency cell
      populations may be hidden and wrongly interpreted. Analysis of the cytome is of
      pivotal importance in basic research for the understanding of cells and their
      interrelations in complex environments like tissues and in predictive medicine
      where it is a prerequisite for individualised preventive therapy. Analysis of
      molecular phenotypes requires instrumentation that on the one hand provides high
      throughput measurement of individual cells and is on the other hand highly
      multiplexed, enabling the simultaneous acquisition of many parameters on the
      single cell level. Upcoming technology suitable to this task, such as slide based
      cytometry is available or under development. The realisation of cytomic
      technology is important for the realisation of the human cytome project.

PMID- 15471210
TI  - Low-dose ionizing radiation exposure: understanding the risk for cellular
      transformation.
AB  - Radiation is energy transfer. When radiation has sufficient energy to remove an
      orbital electron from its atom, an ionized atom is formed, and radiation with the
      capacity to do this is called ionizing radiation. The primary effect of radiation
      is the induction of free radicals and Reactive Oxygen Species (ROS). All the
      molecules in every cell of the body are potential targets, but the final effect
      of radiation will be mainly of concern if the molecule impaired is a molecule
      critical for life. ROS are also generated as a result of the aerobic respiration
      (metabolic ROS) in much larger quantity than from the natural radiation
      background. During evolution, life has developed powerful control and repair
      mechanisms that greatly contribute to minimize the risks associated with the
      generation of free radicals and ROS. At low irradiation doses the probability of
      the risk is therefore proportional to the dose, and the ALARA (As Low As
      Reasonable Achievable) principle seems to be a valuable goal in radioprotection
      policies.

PMID- 15471211
TI  - Cytometric methods to analyze radiation effects.
AB  - Here, we review the most relevant cytometric methods currently used to analyze
      ionizing radiation effects. Particular interest has been devoted to the following
      methods: chromosomal aberrations, micronucleus assay, fluorescence in situ
      hybridization chromosome painting, comet assay, comet-FISH assay as well as flow
      cytometry.

PMID- 15471212
TI  - Sensitivity of germ cells and embryos to ionizing radiation.
AB  - Experiments performed in laboratory animals suggest that ionizing radiation can
      induce DNA damage in the germ cells of exposed individuals and lead to various
      deleterious effects in their progeny, including miscarriage, low birth weight,
      congenital abnormalities and perhaps cancer. However, no clear evidence for such
      effects has been found in epidemiological studies of people exposed to radiation.
      The predicted risks of hereditary effects of any kinds resulting from parental
      exposure to relatively low doses of ionizing radiation remain very low, compared
      to the spontaneous risks in the absence of irradiation. Irradiation of the mouse
      embryo can lead to various effects (lethality, growth retardation, congenital
      abnormalities), depending on the period of gestation at which irradiation occurs.
      In humans, prenatal irradiation has only been exceptionally associated with
      congenital abnormalities, but irradiation between weeks 8-25 has been shown to be
      able to induce severe mental retardation. Although being not proven, the risk of
      developing a childhood cancer following prenatal irradiation may also not be
      excluded. Like for genetic effects, the risk of adverse effects following
      exposure of the embryo to relatively low doses remains quite low compared to the
      natural risks.

PMID- 15471213
TI  - Apoptosis in human ejaculated spermatozoa.
AB  - After the introduction of assays determining apoptosis in human ejaculated
      spermatozoa, several studies have been published about the relationship between
      apoptosis in spermatozoa and semen quality. Apoptosis in spermatozoa is
      significantly correlated with conventional semen quality parameters, but also
      with the outcome of assisted reproductive techniques. The apoptotic process is
      probably set in motion before ejaculation. Determining apoptosis in spermatozoa
      can improve selection criteria in assisted reproduction.

PMID- 15471214
TI  - Micrometastasis in breast cancer and other solid tumors.
AB  - Hematogenous distant metastasis is the leading cause of cancer-related death in
      breast cancer and other solid tumors. By applying sensitive immunocytochemical
      and molecular assays, disseminated tumor cells (DTC) in bone marrow (BM) can be
      detected in 20-40% of cancer patients without any clinical or even
      histopathological signs of metastasis and the presence of these DTC at primary
      diagnosis predicts the subsequent occurrence of overt metastases in bone and
      other organs. cDNA-microarray analysis on primary breast carcinomas from patients
      with and without tumor cells in BM revealed a predominant downregulation of
      potential metastasis-suppressor genes in BM-positive tumors. Thus, dissemination
      of tumor cells appears to be an early process associated with a specific
      molecular signature of the primary tumor.

PMID- 15471215
TI  - The role of adhesion molecules and chemokine receptor CXCR4 (CD184) in small cell
      lung cancer.
AB  - Small-cell lung cancer (SCLC) is a particularly aggressive form of lung cancer.
      Responsible for this highly malignant phenotype is an early and widespread
      metastasis with a high propensity of SCLC cells for bone marrow involvement and
      the ability to develop resistance against chemotherapeutic agents. Tumor cell
      migration and metastasis share many similarities with leukocyte trafficking,
      which is critically regulated by chemokines and adhesion molecules. There is
      growing evidence that the chemokine stromal derived factor-1 (SDF-1/CXCL12) and
      its receptor CXCR4 (CD184) regulate migration and metastasis of a variety of
      cancers including SCLC. SCLC cells express high levels of functional CXCR4
      receptors. Engagement of CXCR4 by CXCL12 leads to an upregulation of integrin
      mediated adhesion in SCLC and other tumor cells. Activation of CXCR4 chemokine
      receptors and integrins on SCLC cells promotes adhesion to accessory cells (such
      as stromal cells) and extracellular matrix molecules within the tumor
      microenvironment. These adhesive interactions result in an increased resistance
      of SCLC cells to chemotherapy. As such, inhibitors of the CXCR4/CXCL12 axis
      and/or integrin activation may increase the chemosensitivity of SCLC cells and
      lead to new therapeutic avenues for patients with SCLC.

PMID- 15471216
TI  - Use of the allogeneic TCR repertoire to enhance anti-tumor immunity.
AB  - It is well established that antigen-specific T lymphocytes can inhibit tumor
      growth in humans and in mice, leading to complete tumor elimination in some
      cases. However, in many cases T cell immunity is unable to successfully control
      tumor progression. Since tumors are derived from normal tissues, most antigens
      are shared with normal tissues, although expression levels are usually elevated
      in malignant cells. Nevertheless, low-level expression in normal cells can be
      sufficient to render autologous T cells tolerant and thus unable to mount
      effective immune responses against tumors. Here, we review how allogeneic T cells
      can be used to isolate T cells that effectively recognise and kill tumor cells,
      but not normal cells with low level of antigen expression. The TCR of allogeneic
      T cells can be introduced into patient T cells to equip them with anti-tumor
      specificity that may not be present in the autologous T cell repertoire.

PMID- 15471217
TI  - Adoptive immuno-gene therapy of cancer with single chain antibody [scFv(Ig)] gene
      modified T lymphocytes.
AB  - Adoptive transfer of antigen-specific T cells has recently shown therapeutic
      successes in the treatment of viral infections and tumors. T cells specific for
      the antigen of interest can be generated in vitro, and adoptively transferred
      back to provide patients with large numbers of immune-competent T cells. Adoptive
      T cell therapy, however, is a patient-tailored treatment that unfortunately is
      not universally applicable to treat viral infections and tumors. We and others
      have demonstrated that the transfer of genes encoding antigen-specific receptors
      into T cells (i.e., genetic retargeting) represents an attractive alternative to
      induce antigen-specific immunity. Currently, we evaluate this concept in a
      clinical protocol to treat patients with metastatic renal cell cancer (RCC) using
      autologous RCC-specific gene-modified T lymphocytes.

PMID- 15471218
TI  - Flow cytometric diagnosis of myelodysplasia and myeloproliferative disorders.
AB  - The current diagnosis of both myelodysplastic syndromes and myeloproliferative
      disorders relies in large part on subtle and subjective morphologic findings and
      the presence of cytogenetic abnormalities. Consequently, diagnosis of these
      disorders is often difficult and tentative with diagnosis at early stages
      representing a particular challenge. There is a need for new diagnostic
      techniques to allow a more definitive and objective diagnosis for these diseases.
      The published literature relating to the potential diagnostic utility of flow
      cytometric immunophenotyping in the diagnosis of myelodysplastic syndromes and
      myeloproliferative disorders is reviewed, and the increasingly important
      contribution of this technique to the diagnosis of these disorders emphasized.

PMID- 15471219
TI  - Detection of minimal residual disease in acute leukemia.
AB  - Detection of minimal residual disease (MRD) has prognostic value in acute
      lymphoblastic leukemia and acute myeloid leukemia. Particularly the evaluation of
      early treatment response has high prognostic value, because this allows
      identification of true low-risk and high-risk patients, who may profit from
      treatment reduction or treatment intensification, respectively. Consequently,
      monitoring of MRD is now being incorporated in many clinical protocols. Analysis
      of MRD in acute leukemia is currently mainly performed using flowcytometric
      immunophenotyping, real-time quantitative (RQ-)PCR analysis of fusion gene
      transcripts, and RQ-PCR analysis of rearranged immunoglobulin and/or T-cell
      receptor genes. These three techniques differ in their applicability and
      sensitivity and it should be noted that MRD results obtained by one method cannot
      yet easily be compared with MRD results obtained by another method. Also between
      laboratories applying the same method, significant variations in MRD results can
      be present. Consequently, multicenter clinical studies with MRD-based treatment
      intervention need standardization of MRD techniques and quality control of MRD
      results.

PMID- 15471220
TI  - Prevalence and characteristics of monoclonal B-cell lymphocytosis (MBL) in
      healthy individuals and the relationship with clinical disease.
AB  - Identifying and characterizing the earliest stages of disease is particularly
      important in disorders such as Chronic Lymphocytic Leukemia (CLL), where the
      initiating oncogenic events are unknown. Improvements in diagnostic technology
      have led to the detection of disease-associated markers in increasing numbers of
      otherwise healthy individuals. However, many of these approaches do not
      necessarily constitute evidence of a neoplastic process: the identification of a
      disease-precursor state requires evidence at several levels. The advent of high
      sensitivity flow cytometry techniques, developed to monitor disease in CLL
      patients undergoing treatment, has allowed accurate enumeration of sub-clinical
      levels of monoclonal B-cells with a CLL phenotype in healthy individuals from the
      general population and CLL families. The age and gender distribution parallels
      that of clinical disease. Emerging evidence confirms the association between the
      aberrant cells in healthy individuals and those in CLL patients at the
      phenotypic, genotypic and clinical level, particularly in families with inherited
      susceptibility. These cells provide a tool for studying the events responsible
      for disease initiation.

PMID- 15471221
TI  - Interaction between clonal plasma cells and the immune system in plasma cell
      dyscrasias.
AB  - The term "monoclonal gammopathy" (MG) includes a group of clonal plasma cell
      disorders, which show heterogeneous clinical behavior. While multiple myeloma
      (MM) and plasma cell leukemia (PCL) are incurable malignant diseases, most
      patients with MG of undetermined significance (MGUS) show an indolent/benign
      clinical course. Evidence has accumulated which supports the role of the bone
      marrow microenvironment in MG. Accordingly, the survival, drug-resistance and
      proliferation of MM cells have been shown to be largely dependent on a supportive
      microenvironment. Among the different environment-associated parameters, those
      related to the status/activity of the immune system are particularly relevant.
      This review focuses on the different ways clonal plasma cells (PC) interact with
      the immune system in different models of MG, to characterize crucial events in
      the development and progression of MG. These advances may support the design of
      novel therapeutic approaches in patients with MG.

PMID- 15471222
TI  - Genetic determinants of platelet function in thromboembolic diseases.
AB  - Within the past decade our understanding of thromboembolic disorders has become
      even more sophisticated as recent discoveries have suggested the influence of
      gene variants on the development of atherosclerotic disease and arterial
      thrombosis. Candidate genes encode proteins involved in processes relevant to
      atherosclerosis, ranging from cholesterol metabolism to arterial thrombosis.
      Platelets are key elements in primary hemostasis, but also in arterial
      thrombosis. Moreover, a number of genetic polymorphisms of platelet proteins may
      also induce gain or loss of function, supporting a role predisposing some
      individuals to thrombotic events. However, after thousands of studies, much
      controversy remains whether individual platelet polymorphisms contribute to an
      increased likelihood of thromboembolic disorders. Although platelet polymorphisms
      are a promising addition to more established cardiovascular risk factors,
      identifying genetic variants as a single cause of cardiovascular disease would be
      an oversimplification; instead, the contribution of these polymorphisms should
      also be considered in the context of a multifactorial disease. Gene-gene and gene
      environment studies would identify specific combinations associated with a high
      risk to suffer from these diseases. The platelet's genetic heterogeneity should
      also be considered in every aspect of clinical medicine, ranging from
      susceptibility to diseases, pathogenesis, and clinical outcome to diversity in
      responses to drug treatment (pharmacogenomics), and bleeding.

PMID- 15471223
TI  - Platelet activation as a marker for in vivo prothrombotic activity: detection by
      flow cytometry.
AB  - Circulating platelets play a pivotal role in hemostasis. The platelet hemostatic
      function involves the direct interaction with damaged vessel walls, and
      circulating coagulation factors, primarily thrombin resulting in platelet
      activation, aggregation and formation of hemostatic plug. Flow cytometry is a
      useful technique for the study of platelet activation in circulating blood.
      Platelet activation markers for ex vivo analysis may include a) activation
      dependent epitopes of the membrane glycoprotein (GP) IIb/IIIa (CD41a) receptor,
      as demonstrated by the binding of activation-specific monoclonal antibodies
      (MoAbs) PAC1, anti-LIBS1 and anti-RIBS); b) the expression of P-selectin (CD62p),
      the alpha-granule GP translocated to the platelet surface following release
      reaction; and c) platelet procoagulant activity, as demonstrated by the binding
      of i) annexin V protein to the prothrombinase-complex (prothrombin, activated
      factor X (Xa) and V (Va)) binding sites on the surface of activated platelets,
      and of ii) MoAbs against activated coagulation factors V and X bound to the
      surface of activated platelets. Using this method, platelet activation as a
      marker for in vivo prothrombotic activity can be demonstrated in various clinical
      conditions including coronary angioplasty, orthostatic challenge in primary
      depression, sickle cell disease in clinical remission and during pain episode,
      and in pregnancy-related hypertension with marked increase during preeclampsia.
      The finding of platelet procoagulant activity is corroborated by increased levels
      of plasma markers for thrombin generation and fibrinolytic activity.

PMID- 15471224
TI  - The AIDS epidemic: the spread of a deadly disease in the biotech era.
AB  - In the last two decades we have witnessed the progression of a newly introduced
      infection in humans. It is sobering that despite a world-wide effort and the
      tremendous progression of technical capabilities and scientific knowledge we are
      still not able to control the global epidemic of HIV. In 2004 more than 40
      million people were infected. Educational approaches to modify risk-taking
      behavior is still the most critical component of prevention and the most
      important measure to limit the spread of the infection. Vaccine development,
      which is still far from promising, is probably the only way to control the
      disease in the future.

PMID- 15471226
TI  - Blood clotting in space.
AB  - We describe herein a novel in vitro approach that can be used effectively to
      obtain valuable insights into the role of platelets, various coagulation proteins
      as well as proteins of the subendothelial extracellular matrix involved in the
      hemostatic and thrombotic processes occurring under microgravity. At difference
      with other experimental approaches proposed in the past our device operates in a
      closed system and under different shear forces, which better mimics flow
      conditions occurring in vessels. Furthermore our device by allowing real time
      monitoring of the thrombotic process and its underlying mechanisms can be
      regarded as a reliable system for the precise assessment of platelet function.

PMID- 15471225
TI  - In vitro selection of HIV and CMV specific T-lymphocytes.
AB  - CMV and HIV produce life-long infections. During CMV infection, cellular
      responses mediated by virus specific CD8 and CD4 lymphocytes are effective, while
      during HIV infection cellular responses are ineffective in the long run. In
      recent years, much work has been carried out to better characterize such
      responses by using different methodologies to define the fine epitope
      specificity, the frequency and the function of specific T-cells. These studies
      have diagnostic and therapeutic implications. In fact, monitoring of specific
      lymphocytes may help define the immune status of the patients for therapeutic
      interventions. Identification of CD8 and CD4 epitopes allows the use of relevant
      peptides for lymphocyte stimulation or for vaccine development. Enumeration of
      specific cells permits a quantitative estimate of the immune response. In vitro
      selection provides large numbers of virus specific T-cells for studies on clonal
      composition, on epitope mapping and on HLA restriction as well as for therapeutic
      immunoreconstitution with ex vivo expanded T-cells.

PMID- 15471227
TI  - Space flight effects on bacterial physiology.
AB  - The study of bacterial behavior under space flight conditions is highly important
      for the early detection of changes in bacterial communities and bacteria with
      medical, environmental, or life support consequences for survival of the crew in
      closed space environments. Although many species of prokaryotes have been studied
      in ground simulation facilities or have been flown in space flights, at present
      only few hard research data are available to predict the effects of cosmic
      radiation, microgravity, vibration and hypervelocity on microbial behavior in
      space flight. The results that are available tend to be fragmentary and often
      lack a classical, controlled experimental context to interpret them. Thus, many
      basic questions concerning the effects of space on microbial behavior have yet to
      be resolved.

PMID- 15471228
TI  - Cell cytometry with a light touch: sorting microscopic matter with an optical
      lattice.
AB  - Lab-on-a-chip design is a key technology for increasing both the reliability and
      the functionality of many different preparation and diagnostic techniques in
      biomedicine. The drive towards ever more integrated lab-on-a-chip designs
      requires increasingly complex microfluidic systems. In order to build these
      systems, non-invasive actuators such as pumps, filters and mixers are required.
      We have demonstrated microfluidic sorting based on a 3D interference pattern,
      formed from multiple coherent laser beams, which has the potential to fulfil all
      the above criteria. By interfering five laser beams from a fibre laser at 1070
      nm, we have formed a 3D optical lattice. When particles flow through the optical
      lattice their trajectories depend upon the force exerted on the particle by the
      optical lattice, in combination with the drag force exerted by the fluid flow.
      Hence, with the strength of a particle's interaction with the lattice determining
      the total force exerted upon it, its trajectory is determined by its physical
      properties. These properties include refractive index, size and shape, giving a
      range of criteria with which to sort an analyte. We have shown separation at 45
      degrees of polymer from silica microspheres (by refractive index), the separation
      of protein microcapsules and the sorting of erythrocytes from lymphocytes. The
      interference pattern can be tailored to the particles and if a blockage occurs,
      the laser can simply be switched off, unlike solid-state micro-sorters, so that
      no jamming occurs. Efficiencies in excess of 95% have been achieved.

PMID- 15471229
TI  - Videomicrofluorometry on living cells and discriminant factorial analysis to
      study cell cycle distributions.
AB  - After a rapid overview of the approaches used to study cell cycle, a fluorescent
      digital imaging microscopy method is proposed. This method is improved by a
      factorial analysis relying on the evaluation of several parameters recorded on
      each living cell. Single lympho-blastoid living cells are labeled with three
      fluorescent markers: Hoechst 33342 for nuclear DNA, Rhodamine 123 for
      mitochondria and Nile Red for plasma membrane. For each cell, morphological and
      functional information parameters are obtained. A typological analysis is used to
      separate control cells into four groups: G0-G1, S, G2+M and polyploid cells Gn.
      These control cells define a learning population used to analyze untreated and
      adriamycine treated cells as supplementary individuals in a discriminant
      factorial analysis. Such an approach allows to accurately evidence the change of
      the values of some cellular parameters.

PMID- 15471230
TI  - Evaluation of real-time PCR data.
AB  - If real-time PCR is to be of much worth to its user, some idea regarding the
      reliability of its data is essential. We discuss here some of the problems
      associated with interpreting numerical real-time PCR data that lend themselves to
      analytical evaluation. We translate into the language of molecular biology some
      of the criteria which are used to evaluate the performance of any new method
      (linearity, precision, specificity, limit of detection and quantification).

PMID- 15471231
TI  - Internal case management program gets injured employees back to work.

PMID- 15471232
TI  - CMs, quality manager team up for better care.

PMID- 15471233
TI  - CM is the glue holding the trauma team together.

PMID- 15471234
TI  - Joint replacement CM helps hospital improve outcomes.

PMID- 15471235
TI  - Clinic serves as a model for care of the uninsured.

PMID- 15471236
TI  - Uninsured cases increase in number, complexity.

PMID- 15471237
TI  - Patient safety alert. 'Safety culture' approach guides health system's efforts.

PMID- 15471238
TI  - Not a minute wasted.

PMID- 15471239
TI  - Board's eye view.

PMID- 15471240
TI  - The faculty of emergency nursing: where next?

PMID- 15471241
TI  - Managing minor injuries.

PMID- 15471242
TI  - Improving assessment of pain in older people.

PMID- 15471243
TI  - Management of pregnant trauma patients.

PMID- 15471244
TI  - Nursing diagnostics and electrocardiogram interpretation in relation to
      thrombolysis.

PMID- 15471245
TI  - Cell-signalling repression in bacterial quorum sensing.
AB  - In this paper we expand on two mathematical models for investigating the role of
      three distinct repression mechanisms within the so-called quorum sensing (QS)
      cell-signalling process of bacterial colonies growing (1) in liquid cultures and
      (2) in biofilms. The repression mechanisms studied are (i) reduction of cell
      signalling molecule (QSM) production by a constitutively produced agent degrading
      the messenger RNA of a crucial enzyme (QSE), (ii) lower QSM production rate due
      to a negative feedback process and (iii) loss of QSMs by binding directly to a
      constitutively produced agent; the first two mechanisms are known to be employed
      by the pathogenic bacterium Pseudomonas aeruginosa and the last is relevant to
      the plant pathogen Agrobacterium tumefaciens. The modelling approach assumes that
      the bacterial colony consists of two sub-populations, namely down- and up
      regulated cells, that differ in the rates at which they produce QSMs, while QSM
      concentration governs the switching between sub-populations. Parameter estimates
      are obtained by curve-fitting experimental data (involving P. aeruginosa growth
      in liquid culture, obtained as part of this study) to solutions of model (1).
      Asymptotic analysis of the model (1) shows that mechanism (i) is necessary, but
      not sufficient, to predict the observed saturation of QSM levels in an
      exponentially growing colony; either mechanism (ii) or (iii) also needs to be
      incorporated to obtain saturation. Consequently, only a fraction of the
      population will become up-regulated. Furthermore, only mechanisms (i) and (iii)
      affect the main timescales for up-regulation. Repression was found to play a less
      significant role in a biofilms, but mechanisms (i)-(iii) were nevertheless found
      to reduce the ultimate up-regulated cell fraction and mechanisms (i) and (iii) to
      increase the timescale for substantial up-regulation and to decrease the wave
      speed of an expanding front of QS activity.

PMID- 15471246
TI  - A unified approach to burst properties of multiconductance single ion channels.
AB  - Patch clamp recordings from ion channels often show bursting behaviour, that is
      periods of repetitive activity, which are noticeably separated from each other by
      periods of inactivity. In this paper, bursting behaviour is considered for a
      general finite state space continuous-time Markov chain model of channel gating,
      allowing for one or more non-zero conductance levels. A unified semi-Markov
      framework, that encompasses both theoretical and empirical bursts, is described
      for analysing a broad range of properties of bursts, including the total charge
      transfer, the number of sojourns at distinct conductance levels and the number of
      openings in a burst, with the results presented when the channel is in
      equilibrium. When the gating mechanism is time reversible, it is shown that the
      distribution and autocorrelation function of each of the above properties are
      necessarily finite linear combinations of exponentially or geometrically decaying
      components with non-negative coefficients. Three methods for choosing a critical
      time for empirical bursts are investigated. The theory is illustrated by
      numerical examples from ryanodine, chloride and nicotinic acetylcholine receptor
      channels, demonstrating the power and flexibility of the methodology, and
      permitting comparison between the methods for choosing the critical time.

PMID- 15471247
TI  - Numerical approximations for an age-structured model of a population dispersing
      in a spatially heterogeneous environment.
AB  - As ecological information on life history and habitat characteristics has become
      more sophisticated, models have become more realistic, and simulation methodology
      has become more important. The numerical analysis of simulation models,
      especially those of complex structured ecological systems, is generally lacking.
      The numerical analysis techniques developed here are to help form a systematic
      basis for a simulation theory for physiologically structured, individual-based
      population models in a spatially heterogeneous habitat. The major thrust of this
      paper is to develop and analyse a finite-difference-finite-element numerical
      approximation scheme for a mathematical model of an age-structured population
      dispersing in a bounded spatial environment in Rn. The numerical scheme applies a
      characteristic finite-difference discretization for the time-age domain and a
      finite-element discretization with numerical integral modifications for the
      spatial domain. The scheme not only provides optimal error estimates from the
      numerical analysis perspective but also produces biologically reasonable
      approximate solutions in that the solutions remain non-negative. The existence
      and boundedness of the non-negative approximate solution are shown, and the
      optimal error estimate is proved.

PMID- 15471248
TI  - Is improved detection of adenocarcinoma in situ by screening a key to reducing
      the incidence of cervical adenocarcinoma?

PMID- 15471249
TI  - Cervical cytology screening history of women diagnosed with adenocarcinoma in
      situ of the cervix: a case-control study.
AB  - OBJECTIVE: To determine whether women diagnosed with adenocarcinoma in situ (AIS)
      of the cervix are as well screened as healthy control women. STUDY DESIGN: A case
      control study was performed (307 cases, 1,228 controls) within a statewide
      registry. Cases consisted of women diagnosed with AIS on histology between 1995
      and 2001. Screening histories were compiled from registry records. Variables of
      interest included number of previous negative Pap smears, time interval since
      last negative Pap smear, median time between previous negative Pap smears,
      proportion of negative Pap smears with an endocervical component and history of
      cervical abnormality. RESULTS: Conditional logistic regression showed that cases
      and controls did not differ significantly in the number of previous negative
      smears or in the median time between previous negative smears. Decreasing time
      since last negative smear was protective against AIS, with controls more likely
      to have had a recent negative smear. There was no difference in the proportion of
      previous negative smears with an endocervical component between cases and
      controls; however, some complex temporal relationships were observed in the
      regression analysis. CONCLUSION: Women who are diagnosed with AIS have a
      screening history similar to that of healthy, control women. The findings are
      consistent with the concept that AIS is predominantly a screening-detected
      disease.

PMID- 15471250
TI  - Cytology of vaginal and uterine sarcomas.
AB  - OBJECTIVE: To retrospectively review, based on cytologic and histopathologic
      findings, the diagnoses of 13 patients with uterine sarcoma and 1 with vaginal
      sarcoma. STUDY DESIGN: There were 8 cases of uterine carcinosarcoma (CS), 2 of
      leiomyosarcoma, 2 of endometrial stromal sarcoma (ESS), 1 of endocervical stromal
      sarcoma (ECSS) and 1 of malignant fibrous histiocytoma (MFH) of the vagina. The
      presence of sarcomatous components was retrospectively investigated by
      microscopic observation of preoperative specimens from the endocervical canal and
      endometrial cells. Characteristic features of sarcomatous cells were then
      investigated by cytodiagnostic micrometry of malignant cells. RESULTS: Of the 14
      patients, 1 with low grade ESS and 1 with homologous CS were diagnosed as
      negative for sarcomatous components. One case of high grade ESS had been
      overlooked, as were 4 cases of CS. Thus, 7 cases (50%) were diagnosed as positive
      for sarcomatous cells by preoperative cytologic observation. Based on these
      findings, 12 of the 14 cases (85.7%) were positive for sarcomatous elements on
      retrospective reexamination of the specimens. CONCLUSION: Careful attention
      should be paid to small sarcomatous cells since cases of ESS or ECSS with such
      cells show morphologic characteristics similar to those of stromatous cells.
      Furthermore, careful microscopic observation of an entire specimen is required to
      avoid misdiagnosis as carcinoma since it is easy to overlook sarcomatous elements
      in smears with carcinosarcoma if there are only a few sarcomatous cells.

PMID- 15471251
TI  - Quantitation of Ki-67 expression in the differential diagnosis of reserve cell
      hyperplasia vs. small cell lung carcinoma.
AB  - OBJECTIVE: To investigate whether the detection of proliferation-associated Ki-67
      antigen may be of value in differentiating between reserve cell hyperplasia (RCH)
      and small cell lung cancer (SCLC). STUDY DESIGN: Retrospectively, 20 Papanicolaou
      stained bronchial brushes or washings from 20 patients were selected. Ten were
      diagnosed as RCH (and had no SCLC in follow-up) and the other 10 as SCLC
      (histologically confirmed). All 20 Papanicolaou-stained slides were restained
      with the monoclonal antibody MIB1, directed against Ki-67 antigen; that simple
      and reliable procedure was described recently. In each specimen 5 coherent cell
      groups were identified, corresponding to RCH or SCLC, respectively; photographed;
      and studied for Ki-67 antigen expression after MIB1 staining of the slides. At
      least 3 cell groups remained in each specimen. The Ki-67 labeling index (LI) of
      the specimens was determined as the number of MIB1-positive cells divided by the
      total number of cells in the remaining cell groups. RESULTS: All cases of SCLC
      showed a mean Ki-67 LI of at least .415 (mean .684, SD .151), whereas in the
      cases with RCH the mean Ki-67 LI never was more than .158 (mean .048, SD .049).
      The difference was highly significant (P<.001, Student's t test). Linear
      discriminant analysis resulted in a classifier with which we were able to
      discriminate correctly between SCLC and RCH in 100% of the 20 bronchial brushings
      and washings. CONCLUSION: The results clearly demonstrate that measuring
      proliferative activity in Papanicolaou-stained bronchial brushings and washings
      by MIB1 restaining of the slides may be of great practical value in accurately
      discriminating RCH from SCLC. The method is simple and can be performed in any
      laboratory that is able to carry out immunocytochemical staining. However, an
      additional (prospective) study with a series of difficult cases is necessary to
      confirm these findings.

PMID- 15471252
TI  - Reporting the presence of significant epithelial atypia in pancreaticobiliary
      brush cytology specimens lacking evidence of obvious carcinoma: impact on
      performance measures.
AB  - OBJECTIVE: To assess the clinical impact of recognizing and reporting the
      presence of significant atypia in brush cytology specimens from the biliary and
      pancreatic ducts lacking obvious features of carcinoma. STUDY DESIGN: Analysis of
      120 pancreaticobiliary brushings from 99 patients over a 4-year period. There
      were 114 bile duct and 6 pancreatic duct specimens obtained via endoscopic
      retrograde cholangiopancreatography at a tertiary care center. RESULTS: Overall
      sensitivity, specificity, accuracy, and positive and negative predictive values
      for carcinoma were 47%, 99%, 79%, 95% and 76%, respectively. When the presence of
      "significant epithelial abnormalities," cancer or cellular atypia less than
      carcinoma, was reported, the overall sensitivity, specificity, accuracy, and
      positive and negative predictive values were 62%, 93%, 82%, 85% and 80%,
      respectively. CONCLUSION: Recognizing and reporting the presence of significant
      epithelial abnormalities in pancreaticobiliary specimens lacking obvious features
      of malignancy in brush cytology specimens led to a modest improvement in
      sensitivity for "significant epithelial abnormalities" and cancer, along with a
      slight decrease in specificity and positive predictive value and slightly
      increased accuracy and negative predictive value. Maintaining high specificity is
      essential to avoiding false positive diagnoses on pancreaticobiliary brush
      cytology.

PMID- 15471253
TI  - Determining when to operate on patients with Hashimoto's thyroiditis with nodular
      lesions: the role of ultrasound-guided fine needle aspiration cytology.
AB  - OBJECTIVE: To elucidate the role of ultrasound-guided fine needle aspiration
      cytology (FNAC) in determining whether to request an operation. STUDY DESIGN:
      Twenty-four consecutive patients (23 women and 1 man) with Hashimoto's
      thyroiditis combined with nodular lesions revealed by ultrasonography were
      included in the study. Ultrasound-guided FNAC was performed on their thyroid
      tissue compatible with Hashimoto's thyroiditis and nodular lesions. RESULTS: Two
      of 24 patients (8.3%) had papillary thyroid cancer, which was diagnosed from
      aspirates of 31 nodular lesions and confirmed by operative pathologic findings.
      CONCLUSION: If a patient with Hashimoto's thyroiditis has nodular lesions shown
      by ultrasonography, ultrasound-guided FNAC is helpful in elucidating the nature
      of the lesion and determining whether to request an operation.

PMID- 15471254
TI  - Utility of immediate evaluation of endoscopic ultrasound-guided transesophageal
      fine needle aspiration of mediastinal lymph nodes.
AB  - OBJECTIVE: To assess the value of immediate cytologic evaluation (ICE) in
      mediastinal endoscopic ultrasound-guided transesophageal fine needle aspiration
      (EUS-FNA). STUDY DESIGN: Fifty eight patients with mediastinal lymphadenopathy
      underwent transesophageal EUS-FNA. Cellularity, number of needle passes and
      number of slides prepared were reviewed retrospectively. RESULTS: Of moderate to
      highly cellular passes, 75% were diagnostic. ICE had a 100% positive predictive
      value and 97% negative predictive value. ICE allowed a diagnosis in all cases.
      Calculated diagnostic accuracy was 70% if the procedure ended after a single
      specimen of at least moderate cellularity or after completion of 4 needle passes.
      CONCLUSION: Immediate cytologic evaluation of EUS-FNA specimens allowed a
      diagnosis in all cases and contributed to the utility of EUS-FNA as a diagnostic
      procedure for mediastinal adenopathy.

PMID- 15471255
TI  - Thyroid transcription factor-1 immunocytochemical staining of pleural fluid
      cytocentrifuge preparations for detection of small cell lung carcinoma.
AB  - OBJECTIVE: To assess whether thyroid transcription factor-1 (TTF-1)
      immunostaining of cytocentrifuge slides previously stained by the Papanicolaou
      technique is feasible and useful in diagnosing small cell lung carcinoma (SCLC)
      in pleural fluid. STUDY DESIGN: Eleven Papanicoalou-stained cytocentrifuge
      preparations of pleural fluid from 11 patients with SCLC were reviewed. The
      initial cytologic diagnoses were 5 positive, 1 suspicious and 5 negativefor SCLC.
      After transferring the cytologic material to a positively charged slide,
      immunostaining was performed using mouse monoclonal antibody against TTF-1.
      RESULTS: The neoplastic cellularity varied among the single suspicious and 5
      positive cases. The case with a suspicious diagnosis had scant tumor cells. All 6
      cases showed nuclear stainingfor TTF-1 in most of the tumor cells. The other 5
      cases with a negative cytologic diagnosis were negativefor TTF-1. CONCLUSION: The
      results of this study indicate that immunostaining for TTF-1 can be successfully
      applied to previously Pap-stained cytocentrifuge preparations to assist in the
      diagnosis of SCLC in pleural fluid.

PMID- 15471256
TI  - Granulocytic sarcoma of the small intestine in a child without leukemia: report
      of a case with cytologic findings and immunophenotyping pitfalls.
AB  - BACKGROUND: Granulocytic sarcoma is a rare tumor that is often misdiagnosed as it
      can be confused with lymphoma. It has unique cytologic features independent of
      the site of the tumor and can be identified on fine needle aspiration. CASE: A 13
      year old girl without a relevant medical history presented with an abdominal
      mass. Investigation revealed a tumor infiltrate in the small intestine and
      mesentery. The fine needle aspirate contained myeloid blasts with cytoplasmic
      granules. Immunohistochemistry on subsequent biopsy confirmed myeloid
      differentiation. There was no evidence of blood or bone marrow involvement
      suggestive of acute leukemia. The patient was well after 27 months of follow-up.
      CONCLUSION: Granulocytic sarcoma should be included in the differential diagnosis
      of any small intestine infiltrate. Cytomorphology is accurate and efficient for
      the diagnosis in conjunction with complete immunocytochemistry study.

PMID- 15471257
TI  - Metastatic carcinoma with myxoid stroma in the salivary gland: a case report.
AB  - BACKGROUND: Most epithelial salivary gland tumors with a myxoid stroma are
      pleomorphic adenomas. Rare metastatic carcinomas have prominent myxoid stroma and
      therefore can mimic pleomorphic adenomas cytologically. CASE: A 62-year-old man
      presented with a left canthal tumor. A biopsy and computed tomography revealed an
      adenocarcinoma of the left ethmoid sinus with medial canthal extension. The
      patient was treated with tumor resection and chemoradiation. An enlarging, left
      parotid mass developed that was reported as a pleomorphic adenoma on a fine
      needle aspirate. However, a parotidectomy showed metastatic adenocarcinoma with a
      myxoid and fibroblastic stroma in an intraparotid lymph node. CONCLUSION: Before
      concluding cytologically that a biphasic epithelial/myxoid stromal salivary gland
      lesion is a pleomorphic adenoma, the patient's previous malignancies should be
      reviewed, and the smears should be scrutinizedfor the absence of diffuse
      epithelial atypia and presence of spindle cells transitional between the 2 tissue
      phases.

PMID- 15471258
TI  - Imprint cytology of extraskeletal mesenchymal chondrosarcoma of the perineum: a
      case report.
AB  - BACKGROUND: Extraskeletal mesenchymal chondrosarcoma (EMC) is an uncommon soft
      tissue tumor, occurring mainly in the lower limbs, meninges and retroperitoneum.
      EMC of the female genital tract is extremely rare, and the cytologic literature
      is scarce. CASE: A 43-year-old female with a growing perineal mass underwent
      excision of the tumor. Pathologic examination of the rumor revealed a
      characteristic two-cell pattern of primitive small cells and cartilaginous
      tissue. A diagnosis of EMC of the perineum was made. Imprint cytology from
      surgical material showed a cluster of small round cells with a focal
      hemangiopericytomalike arrangement and islets of cartilage. The cartilaginous
      cells reacted with S-100 protein immunocytochemically. CONCLUSION: The
      characteristic features of EMC, a hemangiopericytomalike arrangement of small
      cells and S-100-positive cartilaginous cells, may be helpful in diagnosing EMC
      and differentiating it from other perineal tumors.

PMID- 15471259
TI  - Cytologic features of odontogenic myxoma.

PMID- 15471260
TI  - Strongyloides stercoralis as a contaminant in a cervicovaginal smear.

PMID- 15471261
TI  - Nurses look forward to a better deal.

PMID- 15471262
TI  - Nurses are key to sickle cell screening.

PMID- 15471263
TI  - Should we change the law on organ donation?

PMID- 15471265
TI  - How to get ahead in nursing.

PMID- 15471266
TI  - Helping patients to help themselves. Interview by Janis Smy.

PMID- 15471267
TI  - In the line of fire.

PMID- 15471268
TI  - Assessing the value of the internet in health improvement.
AB  - The internet is a powerful tool that provides easy access to information. Many
      people access it for health information and bring the material gathered to health
      appointments. However, the information may not always be correct or adequately
      monitored for quality. This could lead to some of it being harmful. This article
      examines whether or not the internet will enable us to lead healthier lives. The
      need for a quality label, how professionals must become adept at using the
      internet, the possibility of a digital divide exacerbating health inequalities
      and the dangers of misusing the internet's interactive elements are examined.

PMID- 15471269
TI  - What you need to know about...diverticular disease.

PMID- 15471270
TI  - Recognising and managing adult patients who are critically sick.
AB  - The challenge of recognising the ward-based patient at risk of rapid
      deterioration is discussed frequently within the literature. As their role
      enables them to be in constant contact with patients, nurses are in a prime
      position to identify problems at an early stage with the use of systematic
      patient assessment. This means appropriate treatment can be initiated quickly,
      potentially saving the patient's life.

PMID- 15471271
TI  - Evaluating an education project in mental health of older people.
AB  - This article describes the development and evaluation of an education and
      training pathway for older people's mental health. It aimed to increase the
      knowledge and skills of non-specialist NHS-registered and support staff working
      on acute wards for older people. The article makes recommendations to improve
      future training.

PMID- 15471272
TI  - How assessment tools helped me challenge current practice.

PMID- 15471274
TI  - The rewards of being a research nurse. Interview by Craig Kenny.

PMID- 15471273
TI  - Factors influencing the selection of appropriate pain assessment tools.
AB  - Pain is one of the most complex human experiences. Nurses have a moral, ethical,
      humanitarian and professional responsibility to provide an adequate standard of
      pain assessment and documentation. In order to obtain an accurate pain assessment
      from patients, they need to feel that their expression of pain will be listened
      to, accepted and acted on. It is therefore vital that nurses are educated in the
      process of pain assessment.

PMID- 15471276
TI  - Effect of different stimulus frequencies on short-latency somatosensory-evoked
      potentials in patients with focal brain lesions.
AB  - To investigate whether the abnormality of short-latency somatosensory evoked
      potentials(SSEPs)in patients with focal brain lesions is enhanced by different
      stimulus frequencies, the median nerve at the wrist in 10 normal subjects and 12
      patients with cortical (frontal, central and parietal) lesions was stimulated
      electrically at 1.3-18.3 Hz. Normal subjects had decreased frontal P22-N30 and
      parietal P27 amplitudes at high (12.3 and 18.3 Hz) stimulus frequencies, whereas
      the N20 amplitude was relatively preserved. Dissociated loss of frontal P22-N30
      occurred in patients with frontal lesions, but the preserved parietal components
      had characteristics similar to those of the non-affected side or of normal
      subjects at the various stimulus rates, which is evidence of an independent
      pathway for forming the frontal components. A N20 amplitude decrease occurred at
      high stimulus rates in the patients with central lesions, probably because of
      disturbed synaptic transmission. A paradoxical amplitude increase occurred at the
      high stimulus rates in patients with parietal lesions, which is indicative of
      inhibitory function loss in the sensory cortex or thalamo-cortical networks. In
      conclusion, change in the stimulus frequency is a useful method for detecting
      sensory process alteration in patients with focal cortical lesions.

PMID- 15471277
TI  - Successful thromboendarterectomy for severe chronic thromboembolic pulmonary
      hypertension caused by primary antiphospholipid syndrome.
AB  - Pulmonary hypertension is one of the lethal complications in the antiphospholipid
      syndrome due to chronic recurrence of embolism or thrombosis. We experienced a 19
      year-old man suffering from severe chronic thromboembolic pulmonary hypertension
      (CTEPH) caused by primary antiphospholipid syndrome. According to the guideline,
      pulmonary thromboendarterectomy was decided on after combined therapy with
      warfarin, beraprost and oxygen inhalation had not been effective enough to
      improve severe CTEPH. By an operation, the mean pressure of the pulmonary artery
      was decreased from 50 mmHg to 16 mmHg, while his New York Heart Association
      (NYHA) functional class classification significantly improved from class III to
      class I. We concluded that pulmonary thromboendarterectomy could dramatically
      improve hemodynamic indices, NYHA functional status and quality of life in
      patients with CTEPH.

PMID- 15471278
TI  - Preoperative evaluation of trigeminal neuralgia due to epidermoid tumor using a
      three dimensional fast advanced spin echo--case report.
AB  - We report preoperative virtual images reconstructed from three-dimensional fast
      advanced spin echo (3D-FASE)and evaluate the cause of a trigeminal neuralgia due
      to an epidermoid tumor. A 60-year-old man had a 3-year-history of atypical
      trigeminal neuralgia in the left V2 region accompanied by a hypesthesia in the
      cheek. Neuroimaging demonstrated an epidermoid tumor in the left cerebello
      pontine cistern. As the preoperative virtual images reconstructed from 3D-FASE
      images indicated that the superior cerebellar artery compressed the trigeminal
      nerve at the root entry zone, we carried out total removal of the tumor and
      microvascular decompression of the trigeminal nerve. It was possible to visualize
      the fine structures around the trigeminal nerve, because an epidermoid tumor
      shows a high intensity mass on 3D-FASE images. The simulated 3D images were
      useful in deciding upon the additional microvascular decompression surgery for
      trigeminal neuralgia after total removal of the epidermoid tumor.

PMID- 15471279
TI  - [Surgical treatment of medically intractable temporal lobe epilepsy--fundamental
      technique and tips for implantation of intracranial electrodes and tailored
      temporal lobectomy].
AB  - We report a tailored temporal lobectomy for surgical treatment of medically
      intractable temporal lobe epilepsy. Surgery was conducted on 30 patients with
      temporal lobe epilepsy, 15 of whom required intracranial electrode placement. A
      precise skin incision had to be designed when subdural electrodes were placed,
      taking into consideration the electrodes' size and where they should be placed.
      Drawing of the Sylvian line and Rolandic line using Taylor's method on the
      patient's scalp provided useful information to determine the place of craniotomy.
      Fundamental surgical techniques and tips are described, including how to open the
      inferior horn after minimal removal of the lateral temporal cortex, and the
      introduction of a newly developed needle electrode combined with the ring type
      for recording electrocorticography from the exposed hippocampal surface. Twenty
      three patients with mesial temporal epilepsy were treated surgically and the
      surgical results of 20 patients followed-up for more than one year (mean 44
      months)were analyzed. Eighteen patients (90%)were seizure free (Engel class I),
      and 2 patients were categorized as having a significant seizure reduction (class
      III). Despite the good surgical results to date, further follow-up is needed to
      evaluate the long-term surgical effects.

PMID- 15471280
TI  - [Fatigue estimation of visual display terminal (VDT) workers by physiological
      data--preliminary study of a new computer program for VDT work analysis].
AB  - The methods for assessing VDT workload based on individual capabilities are
      necessary to evaluate general fatigue by VDT work. We have developed a new
      computer program for assessing data entry performance of each individual. Four
      healthy male volunteers conducted a data entry task at their own pace using this
      program under a controlled environment. They performed the task for 30 minutes
      twice with 10 minutes rest between them. As a result, the average number of
      inputs was 133.2 characters/min in the first task and 129.1 characters/min after
      taking the rest. The error rate was 8.6% and 10.6% in each task. This program was
      useful to evaluate their data entry performance. We also reported our concern
      with a drop in nasal skin temperature that was observed during these VDT tasks.

PMID- 15471281
TI  - [Vapor-liquid equilibria for multicomponent organic solvents].
AB  - Most organic solvents used in the workplace are mixed solvents consisting of
      several components. It is therefore very important to know the equilibrated vapor
      concentrations in order to control the work environment. In this study, the vapor
      liquid equilibrium for multicomponent organic solvents is estimated by
      introducing the activity coefficients, which are calculated with the UNIFAC
      (Universal Quasichemical Functional Group Activity Coefficient) model. For two
      component solvents, that is, the toluene-methanol and o-xylene-methanol systems,
      the calculated values of the vapor fraction and the equilibrated vapor
      concentrations are in good agreement with the reference ones. For three- or four
      component solvents that are used as thinners, the calculated values are also
      generally in good agreement with the reference ones.

PMID- 15471282
TI  - [Exposure to formaldehyde during an anatomy dissecting course].
AB  - Formaldehyde is a flammable, colorless and readily polymerized gas at ambient
      temperature, and is one of the major pollutants in indoor air. Medical students
      during their dissection course are exposed to formaldehyde, whose exposure is
      recently considered to be one of the causes of multiple chemical sensitivity. To
      understand the system that produces exposures and to plan for implementing
      control options, this study examined formaldehyde exposures that occurred in the
      gross anatomy laboratory. Formaldehyde in air was sampled by an active 2,4
      dinitrophenylhydrazine (DNPH)-silica gel cartridge, extracted with acetonitrile
      and analyzed with an high performance liquid chromatograph-ultraviolet(HPLC
      UV)detector. The geometric mean formaldehyde concentration was 20-93 ppb in the
      anatomy laboratory before starting the anatomy dissecting. After beginning the
      dissecting, however, the highest geometric mean concentrations were 1012-1380
      ppb. Significant differences were observed during the exposed period for symptoms
      of "unusual thirst", "burning eyes", "itchy eyes", "bad feeling", "fatigue", etc.
      in comparison with the non-exposed period. These results show that medical
      schools should take more concrete measures to reduce exposure to formaldehyde.

PMID- 15471283
TI  - [Evaluation of bacterial flora in contaminated soil as a countermeasure against
      H2S gas production].
AB  - Gas productions in illegal dumping sites and waste landfills have caused serious
      problems. The gas production was induced by bacterial flora inhabited soils. In
      order to construct a culture independent evaluation system of the soil bacteria,
      bacterial communities were analyzed quantitatively and qualitatively, about 16
      soil samples at 4 sites, both using culture and culture-independent methods. The
      real time PCR method was developed for counting total bacterial number.
      Sequencing analysis of 16S rDNA amplified by a direct PCR method revealed that
      non-spore forming sulfate reducing bacteria and sulfur-oxidizing bacteria were
      detected at a similar frequency at an illegal dumping site near mountains. On the
      other hand, spore-forming sulfate reducing bacteria and Clostridium sp. were
      mainly detected in deep samples at reclaimed landfills from the sea, whereas
      sulfur-oxidizing bacteria was hardly detected. The result regarding sulfate
      reducing bacteria was confirmed also by an anaerobic culture method. Culture
      independent molecular analyses of soil bacteria would give us useful information
      for prediction of gas production and for the evaluation of soil equilibrium.

PMID- 15471284
TI  - [New developments in the occupational safety and health management system].
AB  - The occupational safety and health management system(OSHMS)has been introduced
      into many companies and factories in Japan. However, there are certain factories
      that are considering the introduction of OSHMS, while other factories are not
      interested in it. In the factories which have introduced OSHMS, occupational
      health activities are still insufficient. Passage by which OSHMS was introduced
      into Japan and a basic way to advance OSHMS is described in this paper. In
      addition, for OSHMS to spread to many companies in the future, and to achieve
      good results, the themes and prospects which should be examined are described.
      The themes shown in this paper are as follows: risk assessment, revision of the
      law and regulation, system auditing, individual management of safety and health
      rules, evaluation of the low concentration exposure influence, appropriate job
      suitability system, training of the expert, the support organization, supporting
      small and medium-sized scale factories.

PMID- 15471285
TI  - [Effect of the Training Program at Occupational Health Training Center (OHTC) on
      the attitude of occupational health residents].
AB  - University of Occupational and Environmental Health (UOEH) conducts three courses
      in postgraduate education of occupational health (OH). Graduates of UOEH who have
      already received a basic education in OH can participate in any course and are
      trained to play an appropriate role as an occupational physician (OP). We operate
      the training program to provide practical knowledge and skills as well as to
      encourage interest in occupational health and to promote a further understanding
      of the role of the OP. In this study we evaluated changes in attitude of
      participants and the effectiveness of our program by an anonymous questionnaire.
      The subjects were all 19 participants of the 3-month program conducted between
      September 2003 and February 2004 as a part of the postgraduate education
      following several years of clinical experience. They were expected to be
      occupational physicians with a clinical specialty. The data were collected from
      questionnaires handed out at the beginning and the end of the program. The
      questionnaire included 8 items on the attitude toward occupational health. The
      subjects answered the questions according to a scale of 1 to 7. Data analysis was
      performed using the unpaired t-test by SPSS. The results suggested that our
      training program had a positive effect on trainees. Interest in occupational
      practice (P < 0.05) and willingness to act as a full-time occupational physician
      in a large company (P < 0.05) increased significantly. When considering the
      positive correlation between willingness to act as an OP and interest in a field
      that has some overlap between the speciality and occupational health, it was
      thought that developing a vision as an OP with respect to their career was
      important for training. However, in some clinical fields it may be difficult to
      define a relationship between the clinical speciality and occupational health.
      Understanding the role of an OP (P < 0.05) and self-confidence in playing an
      appropriate role as an OP (P < 0.05) also showed significant improvement. On the
      other hand, fourteen of the trainees (74%) did not have enough confidence to play
      a role as an OP even after completion of the program. In this study, the
      questionnaire we used was anonymous and did not include items concerning various
      attributes of the subjects. Therefore it was not possible to analyze changes of
      attitude at the individual level. We recognize the need to improve the program
      and are preparing a new version of the educational program with emphasis on
      understanding company organization activities and practical skills for problem
      solving. Opportunities to consider association between clinical speciality and
      occupational health are also included in this new version. We hope that the new
      program will further encourage trainees.

PMID- 15471286
TI  - [Evaluation of students' learning through simulation experience study in
      gerontological nursing education--understanding the elderly person and the role
      of the caregiver].
AB  - The purpose of this study was to clarify the learning of the students who
      participated in an elderly person simulation experience study. We analyzed the
      aspects of the students' understanding of an elderly person and the role of a
      caregiver using the records maintained by the students during their simulation
      experience study. Based on the results, the students' understanding of an elderly
      person was classified under six categories, that is, 1) the physical phenomena of
      aging, 2) the effect of physical phenomena on the activities of daily living
      (ADL), 3) influence of the vital functions on an elderly person's physical
      function and health, 4) the effect on the mental state, 5) the constraint on the
      other persons, and 6) the change in the social status and relationships. The role
      of a caregiver was classified under two categories; that is, 1) the activities
      and role of the caregiver, and 2) the adjustment to the environment. In this
      study, the students perceived not only the physical difficulties but also the
      emotional and sensitivity levels of the aged. In conclusion, it is thought that
      the elderly simulation program is effective in developing a better understanding
      of the physical state of the elderly as well as the importance of providing them
      with support.

PMID- 15471287
TI  - A "See and Treat" approach for high grade squamous intraepithelial lesion on
      cervical cytology.
AB  - OBJECTIVE: To examine the final histologic findings as well as to correlate
      colposcopic and histologic findings in patients who had a high-grade squamous
      intraepithelial lesion (HGSIL) on the Pap smear and underwent colposcopy followed
      by LEEP on the "See and Treat" basis without intervening colposcopically directed
      biopsy. MATERIAL AND METHOD: The medical records of patients with HGSIL on
      cytology who underwent LEEP without prior cervical biopsy at Chiang Mai
      University Hospital over a 5-month period were reviewed. The authors summarized
      the final LEEP histologic results and correlated colposcopic and histologic
      findings in these patients. RESULTS: Of 55 patients who had a see-and-treat LEEP,
      53 patients (96%) had a high-grade intraepithelial lesion or higher. There were
      11 patients (20%) who had invasive squamous cell carcinoma. Of 4 patients with a
      low-grade lesion on colposcopic examination, all had a high-grade lesion or
      higher on final histology. Forty-four patients (96%) with high-grade impression
      on colposcopy had high-grade or more severe lesion on the final histologic
      diagnosis. CONCLUSION: For patients with a high-grade lesion on the Pap smear,
      LEEP according to the "See and Treat" approach appeared to be a reasonable
      alternative to conventional colposcopically directed biopsy, especially in low
      resource settings.

PMID- 15471288
TI  - The incidence of deep vein thrombosis and pulmonary embolism after total knee
      arthroplasty: the screening study by radionuclide venography.
AB  - Deep vein thrombosis (DVT) and pulmonary embolism (PE) are considered uncommon in
      Asian populations and thrombo-prophylaxis is rarely indicated. The objective of
      this study was to investigate the incidence of DVT and PE after total knee
      replacement in an Asian population. MATERIAL AND METHOD: There were 100 patients
      who underwent total knee replacement enrolled in this study. No thrombo
      prophylaxis was given to these patients. The possible risk factors such as age,
      sex, body mass index (BMI), operative time and the post-operative blood loss were
      recorded. RESULTS: The duplex ultrasonography (controlled) showed no evidence of
      DVT in all cases. There were 67 patients who completed radionuclide venography in
      this study. The incidence of DVT from positive radionuclide venography was 24%
      (16/67 patients) and PE was 12% (8/67 patients). All patients with positive
      imaging studies were asymptomatic. The risk factors were similar in both groups.
      CONCLUSION: The incidence of DVT and PE in post-operative total knee replacement
      surgery, although lower than the incidence in Western populations, is higher than
      previously assumed. The radionuclide venography is less invasive and a useful
      diagnostic method for both DVT and PE. Because all patients with DVT and PE are
      asymptomatic, the use of thrombo-prophylaxis should be considered for risk and
      benefit.

PMID- 15471289
TI  - Microsurgical lymphonodovenous implantation for chronic lymphedema.
AB  - This is a prospective study of 10 cases, 14 lower extremities lymphedema were
      treated by microsurgical lymphonodovenous implantation from October 2001 to July
      2003. All of the presented patients suffered from filariasis with obstructive
      lymphedema of the lower limbs. The surgical technique is described. The results
      have been satisfactory. The average reduction in the circumference of the
      affected limb was 7.37 cm at 16 cm below the knee joint level, with an average
      follow up of 4.5 months. Subjective and objective signs were improved.

PMID- 15471290
TI  - Homogeneity of beta(0)-thalassemia codon 17 (A-->T) alleles in Northern Thailand
      using a direct DNA sequencing method.
AB  - The aim of this study was to characterize beta-globin gene micro-haplotype
      polymorphisms (frameworks) associated with a beta-thalassemia mutations common in
      Northern Thailand using a direct DNA sequencing method. A total of 11 beta
      thalassemia major patients homozygous for the codon 17 (A-->T) mutation admitted
      to Chiang Mai University Hospital were examined. All 22 alleles were found to
      contain the Asian framework 3A. The homogeneity of the framework associated with
      the codon 17 (A-->T) mutation indicates a relatively recent origin of the codon
      17 (A-->T) mutation. Similar studies in other East Asian populations may provide
      information concerning the origin and the migrational spread of this beta
      thalassemia mutation.

PMID- 15471291
TI  - Kawasaki disease in central area of Northeast Thailand.
AB  - Kawasaki disease (KD) is a leading cause of acquired heart disease of childhood.
      The authors retrospectively reviewed cases of KD in major referral centers of
      central Northeast Thailand from July 1991 to June 2003. Seventy-three episodes
      occurring in 72 patients were diagnosed with KD by the American Heart Association
      criteria with a mean age of presentation of 27 +/- 19 months. The annual
      incidence was 2.2 per 100,000 children < 5 years of age. Coronary artery
      abnormalities (CAA) were found in 15 (20.5%) children. Nine patients (18%) who
      were diagnosed before 10 days were not treated with intravenous immunoglobulin
      (IVIG). Two (13%) of the 15 patients still had coronary lesions at the end of the
      follow-up period of 35.5 +/- 13.4 months. Index of suspicious should be
      maintained in children who had clinical signs of KD for early diagnosis and
      prompt treatment with IVIG.

PMID- 15471292
TI  - The comparison of conventional pterional and transciliary keyhole approaches: pro
      and con.
AB  - For years, neurosurgical operations have developed. Treatment modalities
      involving new devices and instruments have been innovated. Another principle of
      management that has been created and developed is the approach to enter the
      intracranial structure. Yasargil was credited to the standard and may be the most
      important approach, pterional or frontotemporal approach. Many modifications of
      this approach by new neurosurgeons has been created. Until now the concept of
      minimally invasive neurosurgery has been well accepted. The fundamental tendency
      to be as minimally invasive as possible with a minimum of iatrogenic
      traumatization and to achieve a maximum of efficiency in the treatment of a
      patient has existed since the beginning of surgery. The development of
      unconventional or "difficult approaches", which is based on increased knowledge
      of microsurgical anatomy, improved preoperative diagnostic techniques, and well
      adapted microsurgical instruments, definitely forms one important aspect of
      "refinement in microneurosurgical operating". The supraorbital keyhole via the
      eyebrow incision is one of the minimally invasive approaches. Until now, there
      are debates between the advantage and disadvantage of this approach. The authors
      present the comparative approaches between these young and old methods. The pros
      and cons are listed in detail.

PMID- 15471293
TI  - Cerebrospinal fluid analysis: a predictor of chronic hydrocephalus following
      spontaneous subarachnoid hemorrhage.
AB  - Hydrocephalus is a well-recognized condition following spontaneous subarachnoid
      hemorrhage (SSAH). Ninety-one medical records of patients who presented with SSAH
      were reviewed, 56 patients were included in this study. The amount of red blood
      cells (RBCs) in the cerebrospinal fluid (CSF) and the occurrence of chronic
      hydrocephalus requiring shunt placement were analyzed. In the group that did not
      require shunt placement, the average amount of RBCs in the CSF was 45,823 +/-
      48,789 cells/mm3, whereas, in the shunted group (total of 15 patients) it was
      86,788 +/- 71,045 cells/mm3 which was statistical significantly higher than the
      non-shunted group (p < 0.05). The authors concluded that CSF analysis is a useful
      predictor for shunt placement following SSAH.

PMID- 15471294
TI  - Contralateral total knee arthroplasty after unilateral surgery in bilateral varus
      gonathrosis.
AB  - The authors retrospectively evaluated the rate of contralateral total knee
      arthroplasty (TKA) in 93 patients who had bilateral varus gonarthrosis and
      underwent unilateral TKA. Patients were divided into 3 groups according to degree
      of anatomical varus of the contralateral knee and/or contralateral knee pain at
      the time of first TKA. Group A, 25 patients, had no pain and within 10-degree
      deformity. Group B, 48 patients, had pain and within 10-degree deformity. Group
      C, 20 patients, had pain and more than 10-degree deformity. At a minimum of 2
      years follow up after the first TKA, the mean function scores among the groups
      were significantly different (p < 0.0001). Seventy-five percent of group C, 34%
      of group B and 0% of group A underwent sequential contralateral TKA, respectively
      at average 6.7-month interval. Rate of contralateral TKA was high if patients had
      contralateral knee pain and more than 10 degrees of anatomical varus.

PMID- 15471295
TI  - Development and validation of a new clinical risk index for prediction of
      osteoporosis in Thai women.
AB  - The objective of this study was to develop and validate a new simple tool for
      identifying Thai women who are at high risk of having osteoporosis. A total of
      322 women, aged > or = 45 years, were randomly divided into two cohorts: a
      development (n = 130) and a validation cohort (n = 192). Femoral neck and lumbar
      spine BMD were measured by LUNAR DPX-IQ densitometer. The prevalence of
      osteoporosis (defined by BMD T-scores < or = -2.5) was 33 per cent by either
      femoral neck or lumbar spine BMD. Khon Kaen Osteoporosis Study (KKOS), scoring
      based on age and weight was calculated and applied to the development cohort.
      Individuals with KKOS score < or = -1 were defined as "high risk"; otherwise a
      "low risk" was defined. In the validation cohort, the sensitivity and specificity
      of KKOS was 70 and 73 per cent, respectively. Furthermore, if the high risk
      individuals identified by KKOS are to be treated, and if the treatment reduces
      fracture incidence by 50 per cent and assuming that treatment cost is 10 bahts
      per day, then the cost to prevent one fracture is estimated to be 466,695 bahts
      per year. These data suggest that although age and body weight can be used to
      identify Thai women who are at high risk of having osteoporosis, its application
      to the general population requires further research to arrive at the optimal cost
      benefit for the community.

PMID- 15471296
TI  - Percutaneous carotid stenting: a novel treatment for carotid artery stenosis.
AB  - BACKGROUND: Stroke is currently a leading cause of physical disability and
      carries a high mortality rate. About 20% of ischemic stroke is caused by carotid
      artery stenosis. Carotid stenting is now another therapeutic modality for the
      treatment of extracranial carotid artery stenosis. MATERIAL AND METHOD: All
      patients who underwent carotid stenting at King Chulalongkorn Memorial Hospital
      from March 2001 to December 2002 were analyzed. The case success was determined
      by residual angiographic stenosis of less than 30% without any major adverse
      cardiovascular events such as death, stroke or emergency re-intervention.
      RESULTS: Carotid stenting was performed in 6 patients with 9 vessels disease.
      Their mean age was 71.8 years. Hypertension was the most common risk factor
      detected in all patients, followed by smoking (83.3%), dyslipidemia (83.3%) and
      diabetes (33.3%). One third of the patients had a prior history of stroke or
      transient ischemic attack and 16.6% occurred within 6 months. Five of six (83.3%)
      had severe coronary disease and required coronary artery bypass grafting after
      successful carotid stenting. The procedures were successful in all patients. The
      average percent of stenosis was reduced from 83.2% to 9.4%. The distal protection
      device was used in one-third of the cases. The average procedure time was 63.6
      minutes and fluoroscopic time was 16.6 minutes. There was no evidence of stroke
      or death after the procedures. Only one (11.1%) developed hypotension and
      bradycardia that required intravenous fluid loading and inotropic support for 24
      hours. CONCLUSION: Carotid stenting at our center is feasible and considered to
      be a safe procedure for the treatment of carotid artery stenosis. This procedure
      is another alternative treatment and may be superior to carotid endarterectomy,
      the standard treatment of carotid artery stenosis.

PMID- 15471297
TI  - Pathology and etiology of 110 consecutively removed aortic valves.
AB  - OBJECTIVES: To study the pathology and determine the etiology and prevalence of
      aortic valve disease from surgically removed aortic valve specimens. MATERIAL AND
      METHOD: All the native surgically excised aortic valves (AV) received from June
      1997 to March 1999 (22 months) were studied macroscopically including cuspal
      measurements and microscopically. By preoperative echocardiographic and
      macroscopic studies, they were classified into functional disorders of
      predominant aortic stenosis (AS), aortic stenosis with regurgitation (AS-AR) and
      predominant aortic regurgitation (AR). The patients' medical records were
      reviewed and the clinical information was extracted. The etiology was determined
      according to the macroscopic, microscopic and clinical findings. RESULTS: Among
      110 AV (76 isolated AV and 34 with concomitant mitral valves from patients aged
      15-96 years, mean age 47.54 years; male:female = 1.39:1) there were 25 AS
      (22.73%), 34 AS-AR (30.91%) and 51 AR (46.36%) cases. Eighty-four (76.36%) were
      tricuspid, 16 (14.54%) were bicuspid and 10 were undetermined. Cuspal
      measurements of each disease were provided and compared. All AS specimens were
      related to moderate to severe calcification and causes included postinflammatory
      disease (14 cases, 56%; age range 38-67 years, mean age 53.29 years, male:female
      = 0.56:1), degenerative calcific change (11 cases, 44%, age range 56-76 years,
      male:female = 1.2:1; mean age 69 years of 5 tricuspid AV and 60.83 years of 6
      bicuspid AV). In AS-AR, 29 cases (85.29%; mean age 47.10 years; male:female =
      1.23:1) were attributable to postinflammatory disease and 5 cases (mean age 70.20
      years; male:female = 1.5:1) to degenerative calcific change. In pure AR, there
      were 21 cases (age range 15-65 years, mean age 29.76 years) of postinflammatory
      disease, 14 cases of infective endocarditis (IE) and postIE (age range 20-63
      years, mean age 42.21 years; all 10 IE cases contained gram positive cocci), 1
      case (age 55 years) of bicuspid calcific change, 8 cases of AV with dilated valve
      ring, 5 cases of miscellaneous causes and 2 cases of indeterminate etiology.
      Aschoff bodies were found in 3 AR cases. Four of 18 postinflammatory AS-AR and 4
      of 14 postinflammatory disease AR cases had past history of rheumatic fever. One
      postinflammatory AS also had infective endocarditis from gram positive cocci
      without clinical sign. Severe degenerative calcific change had a higher incidence
      of underlying diabetes (3 of 15 cases, 20%), hypertension (8 of 14 cases, 57.14%)
      and dyslipoproteinemia (9 of 13 cases, 69.23%) in comparison with 3.37% (3/89)
      for diabetes, 9.09% (8/88) for hypertension and 30.99% (22/71) for
      dyslipoproteinemia in other AV diseases in combination. CONCLUSION: The three
      common causes of severe AV functional disorders were postinflammatory disease
      (58.18%), degenerative calcific change (15.45%) and IE-postIE (12.72%).
      Underlying diseases of severe degenerative calcific change included hypertension,
      dyslipoproteinemia and diabetes. Macroscopic and microscopic examinations
      together with clinical information, echocardiographic findings and operative
      details are important in evaluating the etiology of valvular diseases especially
      in severely calcified specimens.

PMID- 15471298
TI  - Serological study of Mycoplasma pneumoniae infections.
AB  - Mycoplasma pneumoniae antibody was determined in 811 sera of different patients
      admitted to Siriraj Hospital with respiratory tract infection from July 1, 2000
      to August 31, 2003 by agglutination with gelatin particle agglutination test kit
      (SERODIA-MYCO II, Fujirebio Inc. Japan) in microtiter plates. Three hundred and
      three sera were positive (37.36%). The five most positive titer were found in
      patients 5-9 yr (40.26%), followed by patients 1-4 yr (24.75%), 10-14 yr
      (19.80%), 30-39 yr (5.28%) and 20-29 yr (3.96%). The positive titers ranged from
      40 to > 20,480. Female:male ratio in positive patients was approximately the same
      (1.19:1). High titers (> or = 320) were found in 146 out of 303 patients
      (48.18%). The infection was mostly found in children aged 5-9 yr. Detection of
      antibody to M. pneumoniae infection showed that 37.36% of patients who were
      suspected of having atypical bacterial pneumonia were positive.

PMID- 15471299
TI  - Application of subjective global assessment as a screening tool for malnutrition
      in pediatric surgical patients.
AB  - OBJECTIVES: To determine the incidence of malnutrition in the pediatric surgical
      ward and to evaluate the value of SGA as a nutrition assessment tool in this
      patient group. PATIENTS AND METHOD: Consecutive pediatric patients aged 2 months
      16 years who were admitted for an operation in the pediatric surgical ward,
      Songklanagarind Hospital from February to September 2001 were included.
      Nutritional assessment was performed for each case, using a translated version of
      the SGA questionnaire. Anthropometric measurements and laboratory tests were
      performed as a routine pre-operative evaluation. The result of the SGA ratings
      were tested against the other parameters and Gomez's weight for age (W/A)
      criteria for protein energy malnutrition. SGA and the other parameters were
      tested for association with post-operative infectious complications. Each SGA
      question was analyzed by multivariate logistic regression analysis, to determine
      an independent correlation between the question item and final SGA rating.
      RESULTS: The study included 78 patients. At least one item of SGA history was
      positive in 28 cases (35.9%). The SGA rating was class A in 50 cases (64.1%),
      class B in 17 cases and class C in 11 cases. According to the Gomez
      classification, 42 cases (53.8%) were considered normal or overweight, whereas 23
      cases (29.5%) were in the first degree underweight, 9 cases were in the second
      degree and 4 cases were in the third degree. Malnutrition by SGA rating
      correlated significantly with Gomez's second and third degree malnutrition, lower
      z-score, lower BMI and hypoalbuminemia. Malnutrition by SGA rating and
      hypoalbuminemia were associated with increased risk of an infectious
      complication, whereas a significant relation between a complication and
      anthropometric malnutrition could not be demonstrated. Moreover, SGA malnutrition
      was significantly associated with a longer post-operative stay. Among 5 items of
      SGA questions, history of weight change in the recent 2 weeks and increased
      energy need considered by an underlying disease were found to be independently
      associated with a final SGA rating of malnutrition. History of weight loss and
      gastrointestinal symptoms were the 2 most sensitive questions. CONCLUSIONS: SGA
      is a sensitive and specific nutrition assessment tool useful in a pre-operative
      pediatric setting. Application of the protocol as a complement of standard
      anthropometric tool should be considered.

PMID- 15471300
TI  - Percutaneous endopyelotomy in the treatment of ureteropelvic junction
      obstruction.
AB  - INTRODUCTION: Current advances in endourology, percutaneous endopyelotomy has now
      become the preferred treatment for ureteropelvic junction obstruction. Many
      advantages of endopyelotomy compared to open correction are decreasing
      postoperative pain, shorter operative time and short recovery time. PATIENTS AND
      METHOD: Percutaneous endopyelotomy was performed in 15 patients. Nine patients
      had previous open kidney and upper ureteral surgery. 11 patients had associated
      renal calculi. The incised ureteropelvic junction was stented with an
      endopyelotomy stent size 14/7 F. The stent was removed 6 weeks postoperatively.
      RESULTS: 14 patients (93%) remain symptom-free and 11 (73%) had improvement of
      their symptoms and postoperative intravenous pyelogram or renogram after follow
      up at 12-38 months (over 18 months). CONCLUSION: Percutaneous endopyelotomy is
      widely accepted as the first choice for correction of ureteropelvic junction
      obstruction due to less morbidity and with a high success rate.

PMID- 15471301
TI  - Mortality analysis of HIV-1 infected patients for prioritizing antiretroviral
      drug therapy.
AB  - Mortality data of patients, classified according to their clinical status and
      CD4+ cell count status, would be very useful to guide clinicians to prioritizing
      patients who need antiretroviral drug therapy. In the current study, the authors
      re-analyzed data derived from a previously published retrospective study of HIV-1
      infected individuals at Lampang Hospital in northern Thailand. According to the
      Cox proportional hazard model, compared to asymptomatic patients with a high CD4+
      cell count (> 200 cell/microl), the mortality rate of asymptomatic patients with
      a medium CD4+ cell count (100-199 cell/microl) did not significantly differ.
      However, the mortality rate of patients with a CD4+ cell count below 100
      cell/microl was at least 16 times higher, regardless of the presence of clinical
      symptoms. Based on these results, the authors produced a Lampang Hospital
      guideline of antiretroviral drug use; priority of antiretroviral therapy should,
      therefore, be given to patients with CD4+ cell count < 100 cell/microl.

PMID- 15471302
TI  - Cost analysis of laboratory tests: a study of the Central Laboratory of King
      Chulalongkorn Memorial Hospital.
AB  - OBJECTIVES: To present cost analysis on laboratory management of laboratory tests
      provided by the Central Laboratory of King Chulalongkorn Memorial Hospital
      (KCMH). MATERIAL AND METHOD: The expenditure and income of the laboratory were
      studied using a descriptive design. RESULTS: The Central Laboratory provided
      routine hematology, urinalysis, and chemistry tests, and performed 2,157,275
      tests in year 2002. The expenditure of the Central Laboratory was 32,094,960.24
      baht, while the income was 97,393,244.40 baht. The average calculated
      profitability ratio for all parameters was 3.03. CONCLUSION: The authors
      concluded that the Central Laboratory is a good Revenue Producing Cost Center
      (RPCC) for the hospital. To improve the laboratory efficiency, the data needed
      for laboratory management should be easily available to the laboratory manager.
      In addition, the authors strongly suggest that the organization structure and the
      data management system of the hospital and the faculty should be simplified for
      future management. In addition, all laboratories should perform their own cost
      analysis.

PMID- 15471303
TI  - Occurrence and protective level of influenza infections using serology in
      patients with COPD in vaccination study.
AB  - OBJECTIVE: To investigate the prevalence, occurrence and protective level of
      influenza infections using serology in patients with chronic obstructive
      pulmonary disease (COPD) during a one-year influenza vaccination study. MATERIAL
      AND METHOD: A total of 123 patients with COPD were enrolled during the period of
      1997 to 1998. There were 61 patients in the vaccine group and 62 patients in the
      placebo group with a mean age +/- SD of 67.6 +/- 8.0 and 69.1 +/- 7.5,
      respectively. The vaccine was composed of influenza A/Texas/36/91 (H1N1),
      A/Nanchang/933/95 (H3N2) and B/Harbin/07/94 strains. Antibodies to influenza
      viruses were detected by hemagglutination inhibition (HI) test using antigens of
      vaccine strains. RESULTS: The incidence of influenza proven by serological
      examination was 22/123 (17.9%) cases. Among 17/62 (27.4%) influenza cases in the
      placebo group representing natural infections, 3 (17.6%) were diagnosed as A
      (H1N1), 8 (47.1%) as A (H3N2), 3 (17.6%) as type A, 1 (5.9%) as type B and 2
      (11.8%) as untypeable viruses. The 8.2% of influenza cases found in the vaccine
      group was significantly lower than 27.4% of that in the placebo group (Chi-square
      test, p = 0.01). The protection rate of influenza vaccination was 71%. Among 23
      acute blood samples from 22 influenza cases, the titers ranged from < 10 to 20
      corresponding to its type/subtype. In the vaccine group, 5 influenza cases
      occurred at 7, 7, 10, 11 and 11 months after vaccination. The HI antibodies to
      influenza A (H1N1), A (H3N2) and B viruses at titers of > or = 10 vs > or = 40
      were 50.4% vs 21.9%, 54.5% vs 28.5% and 17.9% vs 4.1%, respectively. CONCLUSION:
      The findings indicated that from 1997 to 1998, the occurrence of influenza as
      natural infection was 27.4%. Influenza A (H3N2) was more frequently prevalent
      than A (H1N1) and B viruses. The influenza vaccination in COPD patients was
      effective. The protective HI antibody titers were > or = 40. The patients without
      protective HI antibody to A (H1N1), A (H3N2) and B viruses were 78.1%, 71.5% and
      95.9%, respectively. Such patients were considered to be at high-risk for
      influenza and recommended to have vaccination.

PMID- 15471304
TI  - Incidence of febrile seizures in thalassemic patients.
AB  - BACKGROUND: Febrile seizures are the most common seizures in children. Their
      incidence is 2-5% or 4.8/1000 person-years. To date, the pathophysiology of
      febrile seizures is unknown. But several hypotheses have been proposed that it
      may relate with plasma iron level. Such low incidence in thalassemic patients
      whose plasma iron level is high could give some clues to this hypothesis.
      PATIENTS AND METHOD: Four hundred and thirty thalassemic patients from the
      hematology clinic at two hospitals in Northeastern Thailand were consecutively
      enrolled between Febuary 2003 and January 2004. The authors reviewed all the
      medical records of the patients and interviewed their parents for occurrence of
      febrile seizures. RESULTS: The patients included 208 males and 222 females with
      an age ranged of 6 months to 10 years (mean = 6.36 years). Twenty patients (4.7%)
      had siblings who had febrile seizures. There were 3 episodes out of 2,734 person
      years. The incidence was 1.10 per 1,000 person-years (95% CI: 0.23 to 3.20). This
      was statistically lower than that of the general population (p-value = 0.002).
      Therefore, the rate in thalassemic patients was 4.4 times less than that of the
      general population (95% confidence interval: 1.4 to 22.6). CONCLUSIONS: The
      incidence of febrile seizures in thalassemic patients was very low compared to
      that of the general children population. Thus, iron overload may be a major
      factor involving the brain metabolism that prevents febrile seizures.

PMID- 15471305
TI  - EBV and hemophagocytic syndrome: analysis of 3 cases, with speculation on
      clinical features, therapy and role of EBV.
AB  - The authors report three patients diagnosed with EBV associated HPCS. The first
      case died of a fatal EBV infection. The second and third cases had primary
      disease of malignant lymphoma. In case 2, T cell lymphoma associated HPCS was
      diagnosed early. However, despite the aggressive treatment of HPCS and T-cell
      lymphoma, the patient died because of the refractory lymphoma. In case 3, HPCS
      and B malignant lymphoma were diagnosed at post mortem. EBV was found very late
      in all three cases. Case 1 and case 2 had a very high DNA-EBV load in blood. Case
      3 demonstrated EBV-RNA encoded antigen (EBER) in lymph node by in situ
      hybridization technique. The clinical features of HPCS were analysed. Four early
      manifestations in these three cases were emphasized, namely fever, splenomegaly,
      progressive pancytopenia and impaired liver function test without severe
      jaundice. The authors stress the most important factor to save the life of the
      patients is to give early diagnosis and early proper management of HPCS as well
      as the etiologic diseases. The treatment of choice of early HPCS are pulse
      corticosteroid, IVIgG. Combination immunochemotherapy including pulse
      corsticosteroid, IVIgG, cyclosporin A, etoposide and plasma exchange should be
      given promptly in severe cases. From the present report, it indicates that the
      association of EBV with HPCS is not uncommon in Thailand. EBV is very important
      because it gives a very poor prognosis either by being an etiologic cause of HPCS
      or by association with ML with HPCS. Clinicians should be aware of EBV and
      recognize it early. The early treatment of EBV should helpfully changes the
      prognosis of the patients. The role of EBV on the occurrence of HPCS and T-ML is
      also discussed

PMID- 15471306
TI  - Diencephalic syndrome: a rare and easily overlooked cause of failure to thrive.
AB  - BACKGROUND: Diencephalic syndrome (DS) is an uncommon cause of failure to thrive
      in infants and young children. The major manifestations are emaciation,
      hyperkinesia, and euphoria. Most patients have a tumor in the hypothalamic-optic
      chiasma region. CASE REPORT: Two children, aged 14 months and 5 years 9 months,
      who presented with classic features of DS at an onset of 2 and 3 months
      respectively, were reported. Neurologic examination was normal, except for
      papilledema in the second child. Imaging of the brain showed a suprasellar mass,
      identified as pilocytic astrocytoma in both cases. The first case was lost to
      follow up. The latter underwent partial resection of the tumor and received
      radiotherapy postoperatively. He gradually gained in weight and height.
      CONCLUSION: DS should be a differential diagnosis in any children with emaciation
      despite adequate caloric intake and an inappropriately euphoric mood. Awareness
      of this syndrome, careful history taking, general detail as well as neurological
      examination including fundoscopic examination and appropriated investigations are
      crucial.

PMID- 15471307
TI  - Mucoepidermoid carcinoma of the lung presenting as a cavitary lesion.
AB  - The authors describe a 62-year-old female patient who presented with a
      progressively enlarging cavitary lesion in the right upper lobe of the lung. Acid
      fast bacilli were recovered from a bronchial washing fluid and identified as
      Mycobacterium tuberculosis. She received antituberculous therapy for 5 months
      without improvement in her clinical symptoms and chest radiograph. A lobectomy
      was performed and pathological review demonstrated a high-grade mucoepidermoid
      lung carcinoma with extensive central necrosis. Staging revealed metastases in
      her left adrenal gland, kidney and spine. High-grade mucoepidermoid carcinoma of
      the lung may present as a cavitary lesion. The presence of M. tuberculosis should
      not preclude clinicians from pursuing adequate diagnostic procedures for a
      possible malignant lesion.

PMID- 15471308
TI  - Aortoesophageal fistula: a life-threatening cause of upper gastrointestinal
      hemorrhage in double aortic arch, a case report.
AB  - The authors present the case of a 2-month-old infant with double aortic arch that
      developed massive bright red upper gastrointestinal hemorrhage from
      aortoesophageal fistula (AEF) after prolonged endotracheal and nasogastric
      intubation. Emergency thoracotomy with AEF and double aortic arch repaired were
      done successfully under cardiopulmonary bypass. Due to tracheomalacia and left
      phrenic nerve injury, tracheal extubation could not be done until 1 month after
      correction of the vascular ring. The endotracheal and nasogastric tube led to
      fistula formation by compression of the esophageal wall against an abnormal
      double aortic arch. When a double aortic arch is suspected, prolonged nasogastric
      intubation should be avoided.

PMID- 15471309
TI  - Nutritional problem of children and youth from a pediatrician's perspective.

PMID- 15471310
TI  - Authorship.

PMID- 15471311
TI  - Volunteers: help in plain sight.
AB  - Hospital volunteers no longer fit the stereotypic patient escort and "candy
      striper" roles. Find out how to make the best use of the talents of newly retired
      Baby Boomers, downsized executives and other community helpers you may have
      overlooked.

PMID- 15471312
TI  - How to respond to a qui tam lawsuit.
AB  - Whistle-blowers, i.e., current or former employees who report believed fraudulent
      hospital claims to the government, are on the rise. The best defense? Beat
      investigators to the punch and do your own sleuthing.

PMID- 15471313
TI  - Governance in the spotlight: what the Sarbanes-Oxley Act means for you.

PMID- 15471314
TI  - Kenni Friedman: a force for change.

PMID- 15471315
TI  - Ten questions for building a physician relations strategy.

PMID- 15471316
TI  - Gazing through the crystal ball: Helicobacter pylori.

PMID- 15471317
TI  - Molecular adsorbent and re-circulating system.
AB  - The molecular adsorbent recirculating system (MARS) is a non-biological
      artificial liver support system. Used for almost a decade, there are only two
      randomized controlled trials on the efficacy of MARS till date. A number of
      uncontrolled studies have documented a marked improvement in the biochemical
      parameters of patients after MARS. Although MARS seems to be an effective and
      promising tool in the management of liver failure, its cost needs to be reduced
      to enable it use in a member of indications.

PMID- 15471318
TI  - Silent gallstones: a therapeutic dilemma.
AB  - Asymptomatic gall stones are defined as stones that have not caused biliary colic
      or other biliary symptoms. Nearly two-third of patients with gall stones are
      asymptomatic. Studies of the natural history of asymptomatic gall stones suggest
      that the cumulative probability of developing biliary colic after 10 years ranges
      from 15% to 25%. The incidence of other complications is much less. The operative
      mortality of elective cholecystectomy is <0.5% but increased mortality is seen in
      elderly persons (>60 year of age), particularly in those with complications such
      as acute cholecystitis. Most decision analysis studies do not favour prophylactic
      cholecystectomy for asymptomatic cholelithiasis. Nonetheless, many studies have
      listed certain criteria for carrying out elective cholecystectomy in asymptomatic
      patients. The authors, from their own experience and after reviewing the
      literature, propose the following criteria for cholecystectomy: life expectancy
      >20 years, calculi >3 cm in diameter, particularly in individuals in geographical
      regions with a high prevalence of gall bladder cancer or calculi <3 mm,
      chronically obliterated cystic duct, non-functioning gallbladder and calcified
      (porcelain) gallbladder. The widespread use of diagnostic abdominal
      ultrasonography has led to the increasing detection of clinically unsuspected
      gall stones. This, in turn, has given rise to a great deal of controversy
      regarding the optimal management of asymptomatic or 'silent' gall stones. While
      cholecystectomy is the undisputed gold standard treatment for symptomatic gall
      stones, the natural history of silent gall stones is not known well enough to
      recommend a definitive therapeutic strategy for such patients. The treatment
      options for asymptomatic or silent gall stones range from no treatment to
      selective cholecystectomy in at-risk group to elective cholecystectomy in all
      patients. There are a large number of proponents for each of these options so
      that each merits careful consideration. In this article, the authors examine the
      evidence for and against treating silent gall stones with the aim of providing
      more specific guidelines for the management of patients found to have
      asymptomatic gall stones.

PMID- 15471319
TI  - Micronutrient antioxidant intake in patients with chronic pancreatitis.
AB  - Increased oxidative stress has been postulated to be an important mechanism in
      the pathophysiology of chronic pancreatitis (CP). Micronutrient deficiency may
      increase the oxidative stress as they assist in free radical clearance. The
      present study was undertaken to assess the intake of micronutrients, i.e.
      vitamins E and C, carotene, selenium, copper, zinc, manganese, magnesium,
      sulphur, riboflavin, methionine and choline in patients with CP. All consecutive
      patients with CP attending the Pancreas Clinic at the All India Institute of
      Medical Sciences were enrolled in the study. The usual dietary intake was
      estimated by the 24-hour dietary recall method and food frequency questionnaire.
      Dietary restrictions, if any, were also noted. The micronutrient intake of
      patients not on any nutritional supplements (n=75, 65 males and 10 females, mean
      age 31.06 +/- 10.64 years) was compared with age- and sex- matched healthy
      controls (n=75). The micronutrients were calculated as per the Nutritive value of
      Indian Foods given by the National Institute of Nutrition, Indian Council of
      Medical Research, India and the US dietary intake guidelines as applicable. It
      was found that the Body Mass Index (BMI) of patients was significantly lower than
      that of healthy controls. The total intake in terms of calorie was lower in
      patients when compared to controls. The dietary intake of vitamin E, riboflavin,
      choline, magnesium, copper manganese and sulfur was significantly lower than that
      of controls as well as the Recommended Dietary Allowance (RDA). Dietary intake of
      selenium and vitamin C was within the limits of the RDA but was lower than that
      of controls, while the intake of carotene was similar in both the groups and met
      the RDA. We conclude that patients with CP had significantly decreased
      micronutrient intake owing to diet modification due to pain. Micronutrient
      deficiency might contribute to increased oxidative stress in these patients.

PMID- 15471320
TI  - C-reactive protein in patients with gallbladder and biliary tract diseases.
AB  - C-reactive protein (CRP) assay is widely used as a clinical tool for the
      evaluation of bacterial infections. No study has been undertaken to evaluate the
      presence of CRP and/or the estimation of this protein in the bile of patients
      with diseases of the gallbladder (GB). In the present study, we estimated the
      quantity of CRP in bile (n=358) as well as serum samples (n=186) obtained from
      patients with GB and biliary tract diseases, using the semiquantitative Avitex
      CRP kit. Bacteriological study was also done on the bile samples. CRP was
      positive in the bile of 56 patients, (15.6%) many of who had bacteriobilia. CRP
      was also present in 49 of the serum samples studied (26.3%). Control serum
      samples did not show any CRP within detectable limits. Hitherto, this is the
      first report that investigated the level of CRP in the bile of patients with GB
      and biliary tract diseases, along with biliary bacterial profile.

PMID- 15471321
TI  - Prevalence of nonalcoholic fatty liver disease in coastal eastern India: a
      preliminary ultrasonographic survey.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a common clinical condition which is
      fast assuming importance as a possible precursor of more serious liver disorders,
      including cirrhosis of the liver and hepatocellular carcinoma. There are no data
      in the published English literature on the prevalence of NAFLD in India. The
      present study was performed to assess a prevalence of NAFLD by ultrasonography in
      a general population in coastal eastern India. Asymptomatic, apparently healthy
      attendants accompanying the patients attending the Gastroenterology outpatient
      were subjected to abdominal ultrasonographic examination for the presence of
      fatty liver; individuals who gave a history of alcohol abuse were excluded from
      the study. The subjects of the study comprised 159 apparently healthy attendants,
      who underwent ultrasonography. Fatty liver was diagnosed by ultrasonography in 39
      of these 159 persons (24.5%). Fatty liver was seen more commonly in males (26.9%)
      than in females (13.8%). Persons with ultrasonographic fatty liver had a higher
      body mass index (BMI) (mean 25.9 +/- 4.17 kg/m2) than persons without fatty liver
      (mean 22.1 +/- 3.27 kg/m2) (p<0.001). The estimated prevalence of NAFLD in an
      unselected apparently healthy and asymptomatic population as detected by
      ultrasonography in our study was found to be 24.5%. This is similar to the
      prevalence rate published from the west. However, contrary to figures from the
      west, males appeared to have a greater predilection for fatty liver than females
      in our study. NAFLD is perhaps as common in developing world as in the developed
      countries despite a lower prevalence of obesity. Indian males may have a greater
      genetic predisposition to developing NAFLD.

PMID- 15471322
TI  - Abdominal cocoon due to primary peritonitis: barium meal is valuable in
      diagnosis.
AB  - Abdominal cocoon, a rare condition in which the small bowel is encased in a
      membrane, resembles peritoneal fibrsis. There are only 16 case reports of this
      condition in the world literature. A 15-year-old girl presented with recurrent
      abdominal pain due to distal small bowel obstruction. Abdominal X-ray showed
      multiple air fluid levels like small intestinal obstruction. Contrast study
      revealed segregation of the small bowel loops with a dilatedproximal small
      intestine and gradual narrowing of the distal ileum with the obstruction; the
      mucosal pattern was preserved till the distal ileum. Contrast was not flowing
      into the colon. At laparotomy, the small intestine was seen to be encased and
      coiled up in a membrane. The membrane was excised, resulting in release of the
      obstruction.

PMID- 15471323
TI  - Acute pancreatitis: presenting manifestation of varicella infection.
AB  - A 29-year-old man presented with symptoms suggestive of acute pancreatitis of 3
      day's duration. No definite aetiology was identifiable at admission. The patient
      had been receiving corticosteroids for the preceding 1 month, after the
      evacuation of a traumatic subdural haematoma. During the hospital stay, he
      developed a macular skin rash, which evolved over a period of 48 hours to a
      papulovesicular rash typical of varicella infection. Liver function tests were
      suggestive of anicteric hepatitis. Acyclovir therapy was instituted. However, the
      patient succumbed to an episode ventricular arrhythmia of sudden onset, possibly
      due to varicella myocarditis. A high index of suspicion for varicella infection
      in immunocompromised patients presenting with acute pancreatitis is necessary for
      early diagnosis. The rash may at times be atypical and may rarely appear after
      the onset of pancreatitis. Whenever any rash develops in the setting of
      pancreatitis of unknown aetiology, rapid diagnostic tests should be undertaken to
      establish the diagnosis and start appropriate therapy.

PMID- 15471324
TI  - Rectal tuberculosis: a rare case.
AB  - A 35-year-old emaciated woman presented with bleeding per rectum with mucoid
      stool due to a rectal growth which clinically mimicked carcinoma rectum. Anterior
      resection and biopsy of the resected specimen proved the case to be one of rectal
      tuberculosis.

PMID- 15471325
TI  - A new technique of postoperative pancreatico gastric enterocutaneous fistula
      repair using de-tubularised afferent loop.
AB  - Postoperative fistula involving upper gastrointestinal tract surgery is a rare
      but troublesome occurrence. Reoperation on these patients is challenging and
      needs to be individualised. Various methods are described including primary
      closure, bypass procedures, serosal patch repair and Roux-en-Y repair. We present
      a new technique of repair using afferent loop that provided a vascularized bowel
      segment, which used in an anatomical fashion for closure of fistula.

PMID- 15471326
TI  - Hilar biliary cystadenocarcinoma: an uncommon hepatic neoplasm.
AB  - Biliary cystadenocarcinoma (BCAC) is a rare cystic tumour of the liver; with its
      benign counterpart, it accounts for <5% of non-parasitic hepatic cysts.
      Preoperative diagnosis of BCAC is difficult; complete surgical excision is
      recommended to prevent recurrence or metastasis. We present the case of a 67-year
      female with centrally located BCAC involving the right hepatic duct and
      distorting the hepatic hilum. This report highlights the difficulties in
      diagnosis, surgical resection, subsequent biliary reconstruction and its outcome.

PMID- 15471327
TI  - Improving outcome in patients of high output small bowel fistula.
AB  - Early and effective control of sepsis is the most important factor determining
      the outcome in patients with enterocutaneous fistulae (ECF). From a retrospective
      analysis of the hospital records (published data), ongoing contamination of the
      peritoneal cavity by the faecal stream was the most important factor leading to
      sepsis and occurred in 75% of patients. The mortality figure in patients with
      high-output ECF was 54.5% and in the presence of sepsis it was 63%. In an attempt
      to reduce these high mortality rates, we conducted a prospective study to
      evaluate the role of the routine use of ileostomy as an ancillary surgical
      procedure for diversion of the faecal stream in patients with high-output small
      bowel fistulae. Data were collected prospectively over a period of 3 years for 31
      patients with high-output small bowel fistulae. On the appearance of the first
      signs of a leak, a laparotomy incision was opened in part or entirely and the
      abdominal collections were drained. Atthe time of exploration ileostomy was
      performed. There were 19 males and 12 females with a age range of 15-34 years
      (mean 30.1 years). All the fistulae were postoperative. Enteric fever was the
      most common aetiology (39%), followed by tuberculosis (35.5%). In 26 patients
      (84%), ileostomy could be done while 5 (16%) were received in moribund state and
      could not be operated on. Nine patients were operated on within 24 hours of the
      leak and 7 (77%) survived. Fifteen patients were operated on between 2 and 5
      days, and 13 (87%) survived. The remaining 2 patients were operated on after 7
      days of the leak and both died. All 5 patients who were not operated on died. The
      overall mortality in patients with high-output small bowel ECFwas 35.5%, which
      was significantly less than themortality figure of 54.5% in a similar group in
      our retrospective study. The mortality in patients undergoing ileostomy was 23%.
      In the postoperative period, surgical wound infection occurred in 100% of
      patients with partial or complete wound dehiscence. Two patients required
      secondary suturing while the remaining healed by secondary intention. Routine use
      of ileostomy for diverting the faecal stream in patients with high-output small
      bowel fistulae was effective in bringing down mortality rates.

PMID- 15471328
TI  - Infant gastroesophageal reflux disease score: reproducibility and validity in a
      developing country.
AB  - A 25-point infant gastro-oesophageal reflux disease (GERD) score based on 11
      signs and symptoms of gastrooesophageal reflux (GER), to diagnose GERD has been
      suggested in infant. We carried out this study to test the reproducibility and
      validity of this scoring system in the cross-cultural settings of Indian infants.
      Caretakers of 610 apparently healthy infants, between the ages of 1 month and 24
      months were administered the Orenstein's infant GER questionnaire and assigned a
      GERD score. Of these, 95 infants were taken up for a 24-hours oesophageal pH
      monitoring study. Before the pH study, each subject was again tested by the
      infant GER questionnaire by another independent observer and assigned an infant
      GERD score. The 24-hours oesophageal pH study was done using the Synectics
      Digitrapper MK III portable pH recording device. Reflux index (RI) >10% in
      infants up to 1 year of age and >5% in children more than 1 year of age was taken
      as pathological. Upper gastrointestinal endoscopy and oesophageal biopsies were
      performed in 35 cases, after taking informed consent. A good correlation was seen
      between the scores evaluated independently by the two workers, with a Pearson
      correlation coefficient of 0.906. The mean GERD score in infants with GER (as
      diagnosed by pH-metry) was 4.64 +/- 3.99 compared to 3.54 +/- 3.96 in those with
      no documented GER (p>0.05). A GERD score of 5 had a sensitivity of 43% and
      specificity of 79%, compared to 86% and 85% observed by Orenstein et al. in their
      series. The infant GER Questionnaire is easily adaptable and reproducible in the
      settings of developing countries. However, its diagnostic validity appears to be
      much less than that obtained by Orenstein et al. in their study on American
      infants.

PMID- 15471330
TI  - Low anorectal malformation associated with sarococcygeal teratoma.
AB  - The association of sacrococcygeal teratoma with anorectal malformation is rare
      event in teratopathogenesis. One such case is described here. The Sacrococcygeal
      teratoma was excised at birth and the low anorectal anomaly was also treated at
      the same time.

PMID- 15471329
TI  - Oesophageal duplication cyst causing neonatal haemoptysis.
AB  - Duplication anomalies of the alimentary tract often present with myriad clinical
      symptoms and signs. There have been no reports of haemoptysis as the presenting
      feature and oesophageal duplication cyst is not considered as a cause for
      haemoptysis. An infant presented with this unusual manifestation. Chest X-ray
      showed persistent right upper zone haziness and contrast enhanced computed
      tomographic scan showed a multiloculated mass on the right side of the chest. The
      cystic mass was excised via a right thoracotomy and dense adhesions were noted
      with the oesophagus. The postoperative period was uneventful and
      histopathological examination revealed it to be a duplication cyst with ectopic
      gastric mucosa. Thus, the diagnosis was made retrospectively.

PMID- 15471331
TI  - Nurses absolved of liability for ER's failure to diagnose stroke.

PMID- 15471332
TI  - Sex harassment of RN by Dr. results in 1.3 million dollar verdict.

PMID- 15471333
TI  - OH: Nurses try to remove 'unremovable' dentures: cracked & hanging teeth impede
      eating--pt. dies.

PMID- 15471334
TI  - MN: 'Melodramatic... female' misdiagnosed: patient 'codes' & dies from
      myocarditis.

PMID- 15471335
TI  - RN sexually assaulted after attempt to render aid on grounds.

PMID- 15471336
TI  - Introductory lecture: nonadiabatic effects in chemical dynamics.
AB  - Recent progress in the theoretical treatment of electronically nonadiabatic
      processes is discussed. First we discuss the generalized Born-Oppenheimer
      approximation, which identifies a subset of strongly coupled states, and the
      relative advantages and disadvantages of adiabatic and diabatic representations
      of the coupled surfaces and their interactions are considered. Ab initio diabatic
      representations that do not require tracking geometric phases or calculating
      singular nonadiabatic nuclear momentum coupling will be presented as one
      promising approach for characterizing the coupled electronic states of polyatomic
      photochemical systems. Such representations can be accomplished by methods based
      on functionals of the adiabatic electronic density matrix and the identification
      of reference orbitals for use in an overlap criterion. Next, four approaches to
      calculating or modeling electronically nonadiabatic dynamics are discussed: (1)
      accurate quantum mechanical scattering calculations, (2) approximate wave packet
      methods, (3) surface hopping, and (4) self-consistent-potential semiclassical
      approaches. The last two of these are particularly useful for polyatomic
      photochemistry, and recent refinements of these approaches will be discussed. For
      example, considerable progress has been achieved in making the surface hopping
      method more applicable to the study of systems with weakly coupled electronic
      states. This includes introducing uncertainty principle considerations to
      alleviate the problem of classically forbidden surface hops and the development
      of an efficient sampling algorithm for low-probability events. A topic whose
      central importance in a number of quantum mechanical fields is becoming more
      widely appreciated is the introduction of decoherence into the quantal degrees of
      freedom to account for the effect of the classical treatment on the other degrees
      of freedom, and we discuss how the introduction of such decoherence into a self
      consistent-potential approximation leads to a reasonably accurate but very
      practical trajectory method for electronically nonadiabatic processes. Finally,
      the performances of several dynamical methods for Landau-Zener-type and Rosen
      Zener-Demkov-type reactive scattering problems are compared.

PMID- 15471337
TI  - Ultrafast temporary charge transfer in pyrrolidinyl-benzonitrile and pyrrolyl
      benzonitrile in the gas phase.
AB  - 4-(N-pyrrolidinyl)benzonitrile and 4-(N-pyrrolyl)benzonitrile were excited by an
      ultrashort pulse at 270 nm to their La (S2) states and then probed by ionization
      at long wavelengths. Parent and fragment ion signals show components with time
      constants < 100 fs which we attribute to ultrafast relaxation to the Lb (S1)
      state. From this short time we infer a conical intersection between the Lb and La
      surfaces. The wave packet can branch there, one part going temporarily to a
      strongly displaced state. Its shift was concluded from an anisotropy observed
      only there. The only excited state known to have a large displacement is the
      charge-transfer (CT) state. The positive anisotropy indicates that the CT state
      belongs to the 2A species for both molecules. For pyrrolylbenzonitrile, this is
      in contrast to previous assignments. The anisotropy, and a coherent oscillation
      observed in pyrrolidinylbenzonitrile, support the idea that the amino-group twist
      is an important component of the CT reaction coordinate.

PMID- 15471338
TI  - Regularized diabatic states and quantum dynamics on intersecting potential energy
      surfaces.
AB  - The importance of diabatic electronic states for a quantum-dynamical treatment of
      conically intersecting potential energy surfaces is well known. An efficient
      construction scheme of approximately diabatic states is discussed which focuses
      on the removal of the singular derivative couplings and often relies on
      information from the potential energy surfaces alone. Thus an accuracy is
      achieved which is comparable to that of the Born-Oppenheimer approximation for
      widely spaced electronic states. New applications are presented for nitrogen
      dioxide and acetylene.

PMID- 15471339
TI  - A resonance-mediated non-adiabatic reaction: F*(2P1/2) + HD --> HF(v' = 3) + D.
AB  - The reaction of F(2P3/2,1/2) + HD --> HF(v' = 3) + D was investigated in a
      rotating-source, crossed-beam machine. The high translational energy resolution
      afforded by the Doppler-selected time-of-flight technique enabled us to
      distinguish the differential attributes of the HF(v' = 3) + D products of the
      ground state (2P3/2) reaction from those due to the spin-orbit excited (2P1/2)
      one. It was found that the F*(2P1/2) reactivity is significantly smaller than
      that for F(2P3/2), and the two state-to-state angular distributions exhibit
      remarkable similarities, though some differences were noted. Comparing the
      results with those concluded previously, we assert that both the adiabatic
      (F(2P3/2) + HD) and, in particular, the non-adiabatic (F*(2P1/2) + HD) reactions
      are predominantly mediated by a resonance mechanism for the formation of the
      HF(v' = 3) + D channel.

PMID- 15471340
TI  - Details and consequences of the nonadiabatic coupling in the Cl(2P) + H2
      reaction.
AB  - In an investigation of nonadiabaticity in the Cl + H2 reaction we examine the
      various coupling terms responsible. By neglecting various of these terms, we show
      that the spin-orbit coupling in the Cl atom is primarily responsible for non Born
      Oppenheimer effects in this reaction, and that the anisotropies in the
      contributing electronic potential energy surfaces as well as Coriolis terms, are
      considerably weaker in their effect. Neglect of all coupling except spin-orbit
      leads to little change in the calculated reaction probabilities both for the Born
      Oppenheimer allowed [Cl(2P3/2) + H2] and Born-Oppenheimer forbidden [Cl(2P1/2) +
      H2] reactions. This implies that one can safely neglect the coupling between
      different values of the electronic projection quantum number omega. Consequently,
      the computational effort involved in an accurate quantum scattering treatment of
      this (and, hopefully, other similar reactions) can be substantially reduced.

PMID- 15471341
TI  - Target isotope effects for vibrationally-resolved electron capture in low-energy
      collisions of O3+ with molecular hydrogen.
AB  - Using a quantum-mechanical molecular-orbital coupled-channel (QMOCC) approach, we
      investigate single electron capture in collisions of O3+ with various molecular
      hydrogen isotopomers (H2, HD, T2) for collision energies of 1 and 100 eV u(-1).
      Potential energy surfaces and nonadiabatic couplings obtained with the spin
      coupled valence-bond method are incorporated into QMOCC calculations of
      vibrationally-resolved cross sections of the product molecular ion. The infinite
      order sudden approximation is adopted and comparisons of the vibrational
      distributions are made with the centroid approximation, which incorporates
      ionization Franck-Condon factors. Intercomparison of the results is used to
      assess the reliability of the approximations and to give insight into the target
      isotope effects.

PMID- 15471342
TI  - Rapid timescale processes and the role of electronic surface coupling in the
      photolysis of diatomic ligands from heme proteins.
AB  - We have observed coherent oscillations of the heme protein myoglobin (Mb)
      following femtosecond laser excitation and photodissociation of the CO, O2, and
      NO bound ligands. Use of a novel methodology, involving "wavelength selective
      modulation" of the pump and/or probe laser pulse train, allows us to discriminate
      between coherences created by pump fields of differing wavelength within the
      laser pulse versus signals that arise from the decay of either vibrational or
      electronic populations. The population driven signals appear when pump field
      interactions having the same optical frequency are allowed to contribute to the
      signal detection channel. One surprising result, which will be stressed in the
      discussion, is the observation of a distinct product state vibrational coherence
      (the iron-histidine stretching vibration of deoxy Mb at 220 cm(-1)) that depends
      upon the presence of pump field interactions having a wavelength mismatch that is
      equal to the 220 cm(-1) vibrational frequency. This observation is surprising
      because the iron-histidine mode is not observed in the resonance Raman
      measurements on the six-coordinate reactant species. Thus, the pump-pulse laser
      excitation between the ground and excited state, which leads to the ligand
      dissociation, is evidently able to create a "field driven" vibrational coherence
      of a resonance Raman inactive mode that extends into non-vertical regions of the
      reactive excited state potential energy surface. Non-radiative electronic surface
      crossing, followed by the rapid development of new electronic forces on the
      nuclei, appears to be ruled out as a source of the coherent signals (the random
      phase of the optically uncoupled modes is one possible explanation for this
      observation). The extremely rapid timescale (<< 150 fs) for the development of
      the (S = 2) high-spin product state of the iron atom from the initial
      unphotolyzed state (S = 0) is worthy of further theoretical discussion because of
      the spin forbidden nature of such a transition. Excited state admixtures of the
      iron spin states are presumably involved, and the mixing of these states, along
      with the unpaired electron on NO, may help to explain the ultrafast time scales
      and large amplitudes that characterize the NO geminate recombination in
      comparison to CO.

PMID- 15471343
TI  - Strickler-Berg analysis of excited singlet state dynamics in DNA and RNA
      nucleosides.
AB  - The excited singlet state lifetime of the ribonucleoside uridine was found to be
      210+/-30 fs by femtosecond transient absorption spectroscopy. This value is
      considerably shorter than all previous time-domain measurements. This result and
      our previous lifetime measurements [see J.-M. L. Pecourt, J. Peon and B. Kohler,
      J. Am. Chem. Soc., 2001, 123, 10 370] for the other common nucleosides are
      compared with lifetimes calculated from available photophysical data using the
      Strickler-Berg (SB) equation. The calculated lifetimes for pyrimidine nucleosides
      are 10-25% lower than the lifetimes measured in femtosecond transient absorption
      experiments. For the purine nucleosides, guanosine and adenosine, consideration
      of just the lowest 1pi --> pi* transition led to predicted lifetimes that are
      three times greater than experimental ones. On the other hand, inclusion of both
      of the lowest energy 1pi --> pi* absorption bands in the SB equation resulted in
      much better agreement with the experimental values. This suggests that both 1pi
      pi* states of the purine nucleosides contribute to their emission. Decay by the
      bright 1pi pi* state (or states, in the case of the purines) is believed to be
      responsible for the experimentally observed lifetimes.

PMID- 15471344
TI  - Conical intersection dynamics in solution: the chromophore of Green Fluorescent
      Protein.
AB  - We use ab initio results to reparameterize a multi-reference semiempirical method
      to reproduce the ground and excited state potential energy surfaces (PESs) for
      the chromophore of Green Fluorescent Protein (GFP). The validity of the new
      parameter set is tested, and the new method is combined with a quantum
      mechanical/molecular mechanical (QM/MM) treatment so that it can be applied in
      the solution phase. Solvent effects on the energetics of the relevant conical
      intersections are explored. We then combine this representation of the ground and
      excited state PESs with the full multiple spawning (FMS) nonadiabatic wavepacket
      dynamics method to simulate the photodynamics of the neutral GFP chromophore in
      both gas and solution phases. In these calculations, the PESs and their
      nonadiabatic couplings are evaluated simultaneously with the nuclear dynamics,
      ie. "on-the-fly". The effect of solvation is seen to be quite dramatic, resulting
      in an order of magnitude decrease in the excited state lifetime. We observe a
      correlated torsion about a double bond and its adjacent single bond in both gas
      and solution phases. This is discussed in the context of previous proposals about
      minimal volume isomerization mechanisms in protein environments.

PMID- 15471345
TI  - Spin-forbidden CO ligand recombination in myoglobin.
AB  - The reaction of small ligands within the distal pocket of haem proteins such as
      myoglobin, to form ligated, low-spin iron complexes is an archetypal spin
      forbidden process in bioinorganic chemistry, because the initial, "deoxy" iron
      complex has a high-spin ground state. Density functional theory (DFT), transition
      state theory (TST), and hybrid DFT/molecular mechanics (QM/MM) calculations are
      reported on the carbon monoxide reaction. Using DFT data for a model compound,
      TST rate calculations at room temperature are carried out which give fair
      agreement with experiment, and suggest a highly non-adiabatic nature to the
      reaction. QM/MM calculations on the whole protein are reported, which are in
      qualitative agreement with the gas-phase model results, but suggest that protein
      matrix effects on the reaction rate may be important.

PMID- 15471346
TI  - Structure of the intersection space associated with ZIE photoisomerization of
      retinal in rhodopsin proteins.
AB  - In this paper we employ a CASSCF/AMBER quantum-mechanics/molecular-mechanics tool
      to map the intersection space (IS) of a protein. In particular, we provide
      evidence that the S1 excited-state potential-energy surface of the visual
      photoreceptor rhodopsin is spanned by an IS segment located right at the bottom
      of the surface. Analysis of the molecular structures of the protein chromophore
      (a protonated Schiff base of retinal) along IS reveals a type of geometrical
      deformation not observed in vacuo. Such a structure suggests that conical
      intersections mediating different photochemical reactions reside along the same
      intersection space. This conjecture is investigated by mapping the intersection
      space of the rhodopsin chromophore model 2-Z-hepta-2,4,6-trieniminium cation and
      of the conjugated hydrocarbon 3-Z-deca-1,3,5,6,7-pentaene.

PMID- 15471347
TI  - Non-adiabatic intramolecular and photodissociation dynamics studied by
      femtosecond time-resolved photoelectron and coincidence imaging spectroscopy.
AB  - Time-resolved photoelectron spectroscopy (TRPES) is emerging as a useful tool for
      the study of non-adiabatic dynamics in isolated polyatomic molecules and clusters
      due to its sensitivity to both electronic and vibrational dynamics. A powerful
      extension of TRPES, coincidence imaging spectroscopy (CIS), based upon
      femtosecond time-resolved 3D momentum vector imaging of both photoions and
      photoelectrons in coincidence, is a new technique for the study of complex
      dissociative processes. Here we show how these spectroscopies can be used to
      study both non-adiabatic intramolecular and photodissociation dynamics in
      polyatomic molecules. Intramolecular dynamics in the alpha, beta-enones acrolein,
      crotonaldehyde and methyl vinyl ketone are studied using both TRPES and laser
      induced fluorescence of HCO(X) product yields. The location of the methyl group
      is seen to have very dramatic effects on the relative electronic relaxation rates
      and the HCO(X) yield. Applying both TRPES and CIS to the 200 nm and 209 nm
      photodissociation of the nitric oxide dimer, (NO)2, we observe the fs time-scale
      evolution of the excited parent neutral via its photoelectron spectrum and the
      emergence of the NO(A) photofragment including its energy and angular
      distributions.

PMID- 15471348
TI  - Experimental observation of competing pathways in the relaxation of ICl* in a He
      supersonic expansion.
AB  - Differing caging mechanisms of electronically excited ICl within He...ICl
      complexes are investigated using laser-induced fluorescence and two-laser, pump
      probe spectroscopy. A continuum signal is observed in laser-induced fluorescence
      spectra recorded with excitation energies that access regions above the I 2P3/2 +
      Cl 2P3/2 dissociation limit. We show that this signal is associated with
      transitions of the He ...ICl(X,v" = 0) complex with a linear equilibrium geometry
      to the continuum of states correlating with the repulsive, inner wall of the
      ICl(A 3pi1) potential. The dissociating ICl(A) molecule within the complex
      undergoes kinematic one-atom caging, ejecting the weakly bound He atom, and re
      stabilizing the molecule in high lying vibrational levels within the A electronic
      state with very little rotational excitation. At higher excitation energies, weak
      LIF features superimposed on the continuum fluorescence signals are observed in
      preliminary investigations. When fixing an excitation laser on one of these
      features, at 18,012 cm(-1), I35Cl(B,v' = 2,3) vibrational levels are formed with
      little rotational excitation. This feature is associated with transitions of the
      linear He...I35Cl(X,v" = 0) complex to intermolecular states associated with the
      ICl(B) diabat that are coupled with those in the ICl(B') adiabat formed by an
      avoided curve crossing. The I35Cl(B,v') products are formed via a non-adiabatic
      one-atom caging mechanism of ICl* molecules within linear He...I35Cl* complexes.

PMID- 15471349
TI  - Photodissociation dynamics of pyrrole: evidence for mode specific dynamics from
      conical intersections.
AB  - The H and D atom elimination mechanisms in the photodissociation of jet cooled
      pyrrole and pyrrole-d1 have been studied by photofragment velocity map imaging.
      The molecules were excited to the 1 1A2 (pi sigma*) state at lambda = 243 nm and
      to the 1 1B2 (pi pi*) state at lambda = 217 nm. H/D atoms were detected by (2 +
      1) resonance enhanced multiphoton ionization (REMPI) at lambda = 243 nm. The
      analysis of the images and the resulting translational energy distributions from
      the 1 1A2 state demonstrates the existence of two decay pathways, fast mode
      specific cleavage of the NH bond in the excited state (channel A) and internal
      conversion (IC) to the electronic ground state (S0) followed by unimolecular
      decomposition of the vibrationally hot S0 molecules (channel B). The angular
      distributions of the H/D atoms from the direct dissociation in the excited state
      are strongly anisotropic, whereas the decay of the S0 molecules leads to
      spatially isotropic distributions. The results at lambda = 217 nm indicate that
      the 1 1B2 state undergoes an ultrafast radiationless transition to 1 1A2 followed
      by the abovementioned direct mode-specific NH bond fission on the 1 1A2 potential
      energy surface (channel A') or conversion to S0 and subsequent unimolecular
      decomposition (channel B'). The latter pathway may also be initiated by a direct
      relaxation from 1 1B2 to S0. The anisotropy parameter of beta approximately -1
      for the direct NH bond fission at lambda = 217 nm is in accordance with the
      expectations for a perpendicular electronic excitation and a dissociation
      lifetime that is short compared to the rotational period of the molecules. The
      fast decay dynamics of both excited electronic states can be rationalized with
      reference to the theoretically predicted conical intersections between the pi
      pi*, pi sigma*, and S0 potential energy surfaces and the antibonding nature of
      the pi sigma* potential energy surface with respect to the NH bond [A. L.
      Sobolewski, W. Domcke. C. Dedonder-Lardeux and C. Jouvet, Phys. Chem. Chem. Phys.
      2002, 4, 1093].

PMID- 15471350
TI  - Time-dependent quantum wave-packet description of the 1pi sigma* photochemistry
      of pyrrole.
AB  - The photoinduced hydrogen elimination reaction in pyrrole via the conical
      intersection of the 1B1 (1pi sigma*) excited state with the electronic ground
      state has been investigated by time-dependent quantum wave-packet dynamics. A two
      dimensional model potential-energy surface has been constructed as a function of
      the NH stretching and the hydrogen out-of-plane bending mode, employing multi
      reference ab initio electronic-structure methods. The branching ratio of the
      reactive flux at the conical intersection has been investigated in dependence on
      the initial vibrational state of the molecule. The results suggest that laser
      control of the photodissociation of pyrrole via mode-specific vibrational
      excitation should be possible.

PMID- 15471351
TI  - New paradigm of transition metal polypyridine complex photochemistry.
AB  - Using polarization sensitive ultrafast transient absorption spectroscopy we have
      studied energy transfer and excited state relaxation pathways in a tetranuclear
      transition metal [(osmium)(ruthenium)3] polypyridine complex. Contrary to the
      generally accepted picture of transition metal complex photochemistry we find
      that ultrafast energy transfer (< or =60 fs) occurs from the excited singlet MLCT
      state of the peripheral Ru-chromophores to the central Os-core, in efficient
      competition with intersystem crossing. Energy transfer between relaxed triplet
      MLCT states is more than an order of magnitude slower (600 fs).

PMID- 15471352
TI  - A novel algorithm for non-adiabatic direct dynamics using variational Gaussian
      wavepackets.
AB  - In a recent paper (G. Worth, P. Hunt and M. Robb, J. Phys. Chem. A, 2003, 107,
      621), we used surface hopping direct dynamics calculations to study the molecular
      dynamics of the butatriene radical cation in the X/A manifold, which is coupled
      by a conical intersection. Here, we present the first direct dynamics
      calculations using a novel algorithm, again using this ideal test system. The
      algorithm, which is based on the powerful multi-configuration time-dependent
      Hartree (MCTDH) wavepacket propagation method, uses a variational basis of
      coupled frozen Gaussian functions that optimally represent the evolving nuclear
      wavepacket at all times. Each Gaussian function follows a "quantum trajectory",
      along which the potential surface is evaluated by quantum chemistry calculations.
      As far fewer Gaussian functions are needed than classical trajectories in a semi
      classical method, the number of quantum chemical calculations is drastically
      reduced. A crucial point in direct dynamics. To validate the method, initial
      calculations have been made using an analytic model Hamiltonian, where it is
      shown to reproduce the main features of the state population transfer with 8-16
      basis functions per state. Coupled to the GAUSSIAN quantum chemistry program, the
      method is then shown to provide a feasible direct dynamics algorithm for the
      description of this non-adiabatic process.

PMID- 15471353
TI  - Marching along ridges. An extrapolatable approach to locating conical
      intersections.
AB  - A conical intersection is a singular point in nuclear coordinate space. As result
      of this singularity the parameters used to search for energy minimized conical
      intersections, energy gradients, energy difference gradients and coupling
      vectors, vary irregularly along the search path. This irregular variation
      precludes the efficient use of extrapolation procedures to speed convergence. In
      this work we show how a previously introduced orthogonalization procedure for the
      branching or g-h space can be used to design search algorithms in which the key
      parameters are slowly varying functions of the search path. From a topographical
      perspective this approach amounts to walking along a path parallel the ridge of
      conical intersections.

PMID- 15471354
TI  - On diabatization and the topological D-matrix: theory and numerical studies of
      the H + H2 system and the C2H2 molecule.
AB  - This article is divided into two main parts: (1) The theoretical part contains a
      new derivation of the topological matrix D (M. Baer and A. Alijah, Chem. Phys.
      Lett., 2000, 319, 489) which is based, solely, on the spatial dependent
      electronic manifold. This derivation enables more intimate relations between the
      adiabatic and the diabatic frameworks as is discussed in detail in the
      manuscript. (2) The numerical part is also divided into two parts: (a) In the
      first part we extend our previous study on the H + H2 system (G. Halasz, A.
      Vibok, A. M. Mebel and M. Baer, J. Chem. Phys., 2003, 118, 3052) by calculating
      the topological matrix for five states (instead of three) and for configuration
      spaces four times larger than before. These studies are expected to yield
      detailed information on the possibility of diabatization of this system. (b) We
      report on preliminary results concerning the C2H2 molecule. So far we established
      the existence of one (1,2) conical intersection and we have good reasons to
      believe that this system contains several (2,3) and (3,4) conical intersections
      as well.

PMID- 15471355
TI  - Time resolved solvent rearrangement dynamics.
AB  - Ultrafast pump-probe studies of I2- recombination in size-selected I2- (CO2)n
      cluster ions demonstrate long time coherent motions in size-selected clusters and
      the resulting non-statistical energy flow in the cluster. For I2-
      photodissociated to produce either I- + I or I- + I*, we identify a solvent
      driven energy transfer process without a condensed phase counterpart. The
      mechanism involved is a Marcus-like solvent-driven curve crossing, with the
      driving force arising from asymmetric solvation, not just from solvent
      orientation. By substituting another halogen for one I atom, we "break" the I2-
      symmetry, and thus obtain direct information on the electron transfer process.
      New experiments on IBr- (CO2)n photodissociation products confirm the behavior
      suspected in the I2- studies. Time-resolved experiments on IBr- and theoretical
      modeling of the dynamics provide quantitative information on the multiple curve
      crossings encountered in the recombination process. In related investigations,
      femtosecond negative ion-neutral-positive ion charge reversal apparatus is
      employed to investigate transient neutral species evolving along a reaction
      coordinate. We report studies of the rearrangement dynamics of Cu(OH2) produced
      by photodetachment of the corresponding anion. Following a controlled delay
      period, a second ultrafast tunable laser pulse initiates resonant multiphoton
      photoionization of the time-evolving Cu...OH2 complex. The time-resolved Cu+ and
      Cu+(OH2) signals provide information both on the prompt dissociation of the
      complex and on energy redistribution between internal rotational and radial modes
      of the evolving complex. Calculations of the time evolution of the anion
      geometric configuration on the neutral potential energy surface yield deeper
      insight into the nature of the rearrangement process and the energy flow within
      the complex.

PMID- 15471356
TI  - Environmental effects on a conical intersection: a model study.
AB  - Excited-state processes at conical intersections (CIs) involving charge transfer
      phenomena can depend sensitively on the influence of a polar and polarizable
      environment. We propose here a formulation to describe the chromophore
      environment interaction for such situations. In a model study, we focus on an
      extension of the two-electron two-orbital model by V. Bonacic-Koutecky, J.
      Koutecky, and J. Michl [Angew. Chem., Int. Ed. Engl., 1987, 26, 170], which
      yields a diabatic model for the S1-S0 CI in protonated Schiff bases and related
      systems, and describes the charge properties and charge translocation phenomena
      associated with this CI. The electrostatic effects of the environment, which are
      expected to strongly affect the CI topology, are accounted for by a dielectric
      continuum model. This translates to the image of free energy surfaces for the
      coupled chromophore-environment system represented by molecular coordinates plus
      a solvent coordinate. The environment's impact on the location and character of
      the CI is investigated. The limiting situations of "frozen" and equilibrium
      solvation effects are examined.

PMID- 15471357
TI  - Triatomic dissociative recombination theory: Jahn-Teller coupling among
      infinitely many Born-Oppenheimer surfaces.
AB  - The coupling of many Rydberg surfaces poses a stringent challenge for theoretical
      description. Yet simplifications arise because quantum defect ideas can be
      applied, which circumvents some of the usual difficulties that arise. We describe
      a theoretical technique capable of handling these complex interactions, which has
      already been applied with success to the dynamics of H3 Rydberg states. The
      extensions necessary to treat the other isotopomers H2D+ and HD2+ are then
      discussed, along with a preliminary application.

PMID- 15471358
TI  - Extraordinary branching ratios in astrophysically important dissociative
      recombination reactions.
AB  - Branching ratios of the dissociative recombination reactions of the
      astrophysically relevant ions DCO+, N2H+ and DOCO+ (as substitute for HOCO+) have
      been measured using the CRYRING storage ring at the Manne Siegbahn Laboratory at
      the University of Stockholm, Sweden. For DCO+, the channel leading to D and CO
      was by far the most important one (branching ratio 0.88), only small
      contributions of the CD + O and OD + C product pathways (branching ratios 0.06
      each) were recorded. In the case of N2H+ the surprising result of a break-up of
      the N-N bond to N and NH (branching ratio 0.64) was found with the branching
      ratio of the N2 + H product channel therefore displaying a branching ratio of
      only 0.36. In the case of DOCO+, the three-body break-up into D + O + CO
      dominated (branching ratio 0.68), whereas the contribution of the CO2 + H channel
      was only minute (0.05). The remaining share (branching ratio 0.27) was taken by
      the pathway leading to OH + CO. For the dissociative recombination of N2H+ and
      DOCO+ also absolute reaction cross sections were obtained in the collisional
      energy range between 0 and 1 eV. From these cross sections it was possible to
      work out the thermal rate constants, which were found to be k(T) = 1.0+/-0.1 x
      10(-7) (T/300 K)(-0.51+/-0.02) cm3 s(-1) and k(T) = 1.2+/-0.1 x 10(-6) (T/300 K)(
      0.64+/-0.02) cm3 S(-1) for N2H+ and DOCO+, respectively.

PMID- 15471359
TI  - Nonadiabatic coupling and vector correlation in dissociation of triatomic
      hydrogen.
AB  - We determine experimentally the vector correlation among the three neutral ground
      state hydrogen atoms which appear in dissociation of neutral H3* molecules. The
      sum of the kinetic energies of the three H-atoms is fixed by selecting the energy
      of the H3* molecule by laser excitation in the range between 0.85 and 3.60 eV.
      The highly structured maps of correlation in the motion of the three atoms
      provide a direct view of the internal molecular couplings which initiate
      dissociation. We discuss this feature in a model calculation and in terms of a
      new quantum chemical calculations of the potential energy surfaces of H3*.

PMID- 15471361
TI  - Increased expression of caspase-1 and interleukin-18 in peripheral blood
      mononuclear cells in patients with multiple sclerosis.
AB  - Multiple sclerosis (MS) is supposedly a T-cell mediated autoimmune disorder of
      the central nervous system. Cytokines and other molecules involved in the
      regulation of apoptosis are thought to be of importance for the pathogenesis of
      MS. In this study, the mRNA levels of interleukin 18 (IL-18), IL-1beta and their
      processing enzyme caspase-1 were quantified by a competitive RT-PCR method in
      unstimulated peripheral blood mononuclear cells (PBMCs) in MS patients never
      treated with disease modifying drugs. Western blot was used to support the
      expression pattern at the protein level. We found that the expression of caspase
      1 and IL-18 was significantly increased in MS patients compared with healthy
      controls. Analysis of clinical subgroups revealed that caspase-1 was increased in
      all subgroups, whereas IL-18 was upregulated in chronic progression (P=0.001) and
      relapsing MS patients in remission (P=0.002) but not significantly during
      relapses (P=0.12). mRNA levels of IL-1beta were not significantly altered in MS
      except for a possible decrease in chronic progression (P=0.03). An increased IL
      18 expression, potentially augmented at the mature protein level, may indicate a
      pathway worth considering in future therapeutic strategies in MS.

PMID- 15471360
TI  - The 14-3-3 protein in multiple sclerosis: a marker of disease severity.
AB  - CONTEXT: In multiple sclerosis (MS) axonal damage is an early event and is
      probably to be considered the most relevant cause of permanent and progressive
      disability. OBJECTIVES: To investigate the value of the increase of 14-3-3 and
      tau proteins in the cerebrospinal fluid (CSF) as peripheral markers of axonal
      pathology and predictors of disease evolution. PATIENTS AND METHODS: In the CSF
      samples obtained from 63 patients with demyelinating diseases (DD), including 20
      clinically isolated syndromes (CIS) and 43 clinically defined MS, as well as from
      56 controls, we analysed the presence of 14-3-3 reactivity by immunoblot analysis
      along with the concentration of tau protein by sandwich ELISA. RESULTS: The
      percentage of DD subjects showing a positive 14-3-3 protein CSF reactivity (38%)
      was significantly higher than the one previously detected, and was correlated in
      the MS patients with a more severe clinical phenotype in terms of degree of
      disability and rate of disease progression, during a 10-month mean clinical
      follow-up. On the contrary, the levels of the CSF-tau protein were highly
      variable in DD and control subjects, and the mean CSF-tau concentration was
      similar in both groups. CONCLUSIONS: The immunoblot analysis of 14-3-3 protein in
      the CSF could be a useful marker to identify a subgroup of DD patients with high
      risk of developing severe disability.

PMID- 15471362
TI  - Bone strength in multiple sclerosis: cortical midtibial speed-of-sound
      assessment.
AB  - It has been previously suggested that multiple sclerosis (MS) patients are at
      increased risk for osteoporosis due to reduced mobility, decreased exposure to
      sunlight and recurrent steroid treatment. In order to systematically evaluate
      bone strength we assessed 256 MS patients (171 females, 75 males) through
      quantitative ultrasound measurement of cortical bone. Tibial speed of sound (SOS,
      m/sec) was measured at midpoint of the tibial shaft using a Soundscan 2000
      (Myriad Ultrasound Systems, Rehovot, Israel) and results were compared to age-
      and gender-matched population norms. T-score distribution in male MS patients was
      similar to normal population. In contrast, for female MS patients T-score
      distribution was significantly different from population norms, reflected by
      increased SOS in 30.4% (T-score intervals 1-2 and >2 above normal values;
      P=0.001), compared with 7.4% in controls. These findings held true for both
      female patients younger and older than 45 years of age. Increased neurological
      disability and specifically motor involvement were more frequent in female
      patients with increased SOS (P<0.05). Bone strength was preserved in MS patients.
      In a subgroup of female patients increased SOS was conceivably related to
      spasticity.

PMID- 15471363
TI  - Ibudilast, a nonselective phosphodiesterase inhibitor, regulates Th1/Th2 balance
      and NKT cell subset in multiple sclerosis.
AB  - We investigated the immunoregulatory effects of ibudilast, a nonselective
      phosphodiesterase inhibitor, at a clinically applicable dose (60 mg/day p.o. for
      four weeks) in multiple sclerosis (MS) patients. Sensitive real-time PCR for
      quantifying cytokine mRNA in the blood CD4+ cells revealed that the ibudilast
      monotherapy significantly reduced tumour necrosis factor-alpha and interferon
      (IFN)-gamma mRNA and the IFN-gamma/interleukin-4 mRNA ratio, suggesting a shift
      in the cytokine profile from Th1 toward Th2 dominancy. In a flow cytometric
      analysis, natural killer T cells, which have been reported to relate to Th2
      responses in MS and its animal model (experimental autoimmune encephalomyelitis),
      increased significantly after the therapy. None of the significant immunological
      changes were seen in healthy subjects or untreated MS patients. Ibudilast may be
      a promising therapy for MS and its clinical effects warrant further study.

PMID- 15471364
TI  - Regulation of differentiation and functional properties of monocytes and monocyte
      derived dendritic cells by interferon beta in multiple sclerosis.
AB  - Interferon beta (IFN beta) has complex immune regulatory properties that
      contribute to its treatment effect on multiple sclerosis (MS). In this study, we
      investigated the role of IFN beta in differentiation and functional properties of
      monocytes and monocyte-derived dendritic cells that are critical to the
      inflammatory process in MS. The results revealed that IFN beta inhibited
      intracellular production of interleukin (IL)-1b (P<0.01) in both monocytes
      exposed to in vitro treatment of IFN beta and monocytes analysed ex vivo from MS
      patients treated with IFN beta. IFN beta was shown to modulate differentiation of
      monocytes into dendritic cells in the presence of IL-4 and GM-CSF, which resulted
      in a delayed differentiation process. Furthermore, it characteristically altered
      the phenotypic features of differentiated dendritic cells by inhibiting the
      expression of CD1a, CD11b, CD11c, CD123 and CD209 while upregulating
      costimulatory molecules, such as CD86. The selective regulatory properties of IFN
      beta appeared to render the function of differentiated dendritic cells to produce
      an increased amount (P<0.01) while their ability to secrete proinflammatory IL-12
      and TGF beta was significantly reduced. The observed collective effects of IFN
      beta seemed to correlate with Th2 immune deviation. The study has provided new
      insights into the regulatory mechanisms of IFN beta in the treatment of MS.

PMID- 15471365
TI  - Interferon-beta: the neutralizing antibody (NAb) titre predicts reversion to NAb
      negativity.
AB  - BACKGROUND: It has been reported that in some patients with MS who develop
      neutralizing antibodies (NAbs) against interferon beta (IFNbeta), antibody levels
      can initially increase and then decrease thereafter even when treatment is
      continued. OBJECTIVE: To determine whether NAb titre correlates with time to
      reversion to NAb negativity in patients with multiple sclerosis (MS). METHODS:
      Twenty-eight patients with MS who were NAb-positive during treatment with one of
      the currently available IFNbetas were included in this retrospective study. NAb
      titres were determined by the myxovirus resistance protein A induction assay.
      Patients were considered NAb-positive if they had at least two consecutive
      samples with titres of > or = 20 neutralizing units (NU). Reversion to NAb
      negative status was defined as two consecutive negative samples (NAb titre of <
      20 NU) after NAb positivity. RESULTS: When measured two years after treatment
      initiation, a NAb titre of < 75 NU had a 91.7% sensitivity and a 87.5%
      specificity for reversion to NAb negativity in the following two years (after a
      total of four years of treatment). In addition, somewhat surprisingly, patients
      whose serum converted to NAb-negative generally developed peak NAb titres earlier
      than patients who remained NAb-positive (mean time of first detection was 21
      versus 38 months, respectively). CONCLUSION: The NAb titre might support
      treatment decisions in patients with MS whose test results are positive for NAbs.

PMID- 15471366
TI  - An open-label safety and drug interaction study of natalizumab (Antegren) in
      combination with interferon-beta (Avonex) in patients with multiple sclerosis.
AB  - In this open-label drug-interaction trial, we studied 38 patients with relapsing
      remitting multiple sclerosis (MS) who received 3.0 or 6.0 mg/kg of natalizumab as
      a single intravenous (i.v.) infusion during stable treatment with intramuscular
      (i.m.) interferon beta-1a 30 microg (IFNbeta-1a; Avonex). To assess the
      pharmacokinetic (PK) interaction of natalizumab and IFNbeta-1a, serum
      concentration-time data for both agents were collected and analysed. Biologic
      response markers of IFNbeta-1a activity, beta2-microglobulin and neopterin, were
      also assessed to determine effects of natalizumab on IFNbeta-1a pharmacodynamics
      (PD). Further, safety and immunogenicity were evaluated. The combination of drug
      therapies was well tolerated. Although natalizumab serum concentrations (and
      corresponding PK exposure measures) appeared to be somewhat elevated in the
      presence of IFNbeta-1a, when compared to the same dose (6.0 mg/kg) administered
      alone in a concurrent comparator study, the differences were generally small and
      unlikely to be clinically relevant. In general, natalizumab had no apparent
      clinically relevant effects on the PK or PD properties of IFNbeta-1a. The
      presence of antibodies to IFNbeta-1a and natalizumab was relatively low. Overall,
      the study provided safety, immunogenicity, PK and PD data to support a
      combination strategy for the use of natalizumab and IFNbeta-1a in the treatment
      of patients with relapsing-remitting MS. A large clinical study is currently in
      progress to evaluate the efficacy and long-term safety of this combination drug
      therapy.

PMID- 15471367
TI  - Guided intrathecal baclofen administration by using soleus stretch reflex in
      moderate-severe spastic multiple sclerosis patients with implanted pump.
AB  - We tested the hypothesis that changes in soleus stretch reflex was correlated to
      changes in intrathecal baclofen dose in 12 multiple sclerosis patients with
      moderate-severe spasticity treated with intrathecal baclofen pump. Twice patients
      were evaluated clinically and biomechanically. The short-latency soleus stretch
      reflex was elicited by rotating the ankle joint 4 degrees with a velocity from
      3.1 to 180 degrees/s. There was a strong correlation between changes in
      intrathecal baclofen dose and amplitude of the short-latency stretch reflex (r=
      0.88, P<0.001), which means that with an increase in baclofen dose there is a
      decrease in the amplitude. In contrast, no correlation exists between changes in
      intrathecal baclofen dose and clinical assessment of spasticity by using the
      Ashworth scale. The amplitude of the stretch reflex was very small (5 microV)
      compared with previous findings (>50 microV), which indicates an effective
      antispastic effect of intrathecal baclofen. We suggest that clinical evaluation
      of spasticity using Ashworth scale is insensitive to detect minor changes in
      moderate-severe spasticity and consequently might not be very useful in
      evaluating spasticity in relation to ambulatory filling of baclofen pumps. The
      soleus stretch reflex might be useful in situations when there is doubt about the
      effect of intrathecally administered baclofen.

PMID- 15471368
TI  - Influence of HLA on progression of optic neuritis to multiple sclerosis: results
      of a four-year follow-up study.
AB  - BACKGROUND: Genetic predisposition in multiple sclerosis (MS) has always been a
      critical concern in aetiology and progress of the disease. The present study
      looks into the relations between human leukocyte antigen (HLA), optic neuritis
      (ON) and MS in the Iranian population. METHODS: Patients with potential diagnosis
      of acute ON underwent a standardized clinical examination for confirming the
      diagnosis. Selected patients were gathered for HLA typing and clinical follow up.
      RESULTS: Of the 55 patients, 46 (83.6%) were female. The mean age was 25(+/-7.3)
      with a range of 12-43. Twenty of the 55 (36%) were confirmed for the diagnosis of
      clinically definite MS (CDMS). Results show that A23, B21, A11 and B51 alleles
      were present in 4 (20%), 6 (30%), 2 (10%) and 1 (5%) of the CDMS patients,
      respectively. Ten (50%) and 17 (85%) CDMS patients were positive for HLA class II
      alleles, DR2 and DQ1, correspondingly. CONCLUSIONS: The study strongly suggests
      the association among DR2, A23 and B21 allele and the evolution of ON to MS. High
      prevalence of A23 and DR2 alleles in CDMS patients compared with the normal
      population may suggest an important role for these alleles in the development of
      MS. The study suggests B51 as a protective factor against development of ON in
      the normal population. In addition, results do not confirm previous studies
      considering A11 as a predisposing factor. The present study finally evokes that
      different classes of HLA have different roles in susceptibility to MS and
      confirms disease heterogeneity as an important emerging concept in MS.

PMID- 15471369
TI  - Mitochondrial haplogroups in Basque multiple sclerosis patients.
AB  - Previous studies have suggested that mitochondrial metabolism and/or
      mitochondrial DNA (mtDNA) could be, in conjunction with other genetic or
      environmental factors, a risk factor for the development of multiple sclerosis
      (MS). One of these studies establishes that mitochondrial haplogroup JT is a risk
      factor for developing the disease, in particular the visual manifestations [optic
      neuritis (ON)]. Nevertheless, as distribution of these haplogroups varies between
      populations, the observed association may be due to a slanted sample with no
      physiopathological value. This hypothesis was checked with MS patients, originals
      from Basque country (this population has peculiar genetic characteristics) and
      from other Spanish regions. We concluded that such an association does not exist.
      By contrast, a decrease could be seen in the frequency of the JT haplogroup in
      the ON group and in the MS-Basque group. That trend could be a protective effect,
      which needs to be verified in further investigations.

PMID- 15471370
TI  - RANTES: a genetic risk marker for multiple sclerosis.
AB  - Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a
      beta-chemokine and has been detected in brain lesions of multiple sclerosis (MS)
      patients. Considering its potential role in MS, we screened two functional
      polymorphisms in the proximal promoter region of the RANTES in MS patients versus
      controls. METHODS: We examined 140 postmortem brain samples from subjects with a
      primary diagnosis of MS, and peripheral blood samples from 216 control subjects.
      The RANTES-28C/G and -403G/A promoter polymorphisms were examined. All subjects
      were non-Hispanic Caucasians. RESULTS: MS cases differed from controls showing a
      significant association with the 403G/A polymorphism (odds ratio, 2.359, [1.465
      3.799]; P=0.0001), but not the -28C/G (P=NS) polymorphism. There was a
      significant association of the -28G allele with both early onset (P=0.031) and
      longer survival (P=0.006). CONCLUSION: There is a significant but complex
      association of the RANTES gene with MS.

PMID- 15471371
TI  - Macrophage brain infiltration in experimental autoimmune encephalomyelitis is not
      completely compromised by suppressed T-cell invasion: in vivo magnetic resonance
      imaging illustration in effective anti-VLA-4 antibody treatment.
AB  - Large inflammatory infiltrates of T cells, macrophages and B cells in the central
      nervous system (CNS) contribute to the pathogenesis of multiple sclerosis (MS).
      The passage of T cells through the blood-brain barrier can be suppressed with
      antibodies directed against alpha-4 integrins (VLA-4) that mediate T-cell
      adherence. This treatment, in phase III of clinical trial evaluation, reduces
      lesion development in MS patients. In the ongoing inflammatory disease process
      the consequences of T-cell inhibitory anti-VLA-4 antibodies on inflammatory
      compounds are still poorly investigated. We show that anti-VLA-4 antibody
      treatment during the late preclinical phase of the acute experimental autoimmune
      encephalomyelitis (EAE) MS rat model interrupts T-cell egress out of the vascular
      compartment and suppresses clinical disease and histological alterations but
      macrophage recruitment in the CNS is not fully compromised. Among the treated EAE
      animals not developing disease, none presented foci of T-cell infiltration in
      CNS. However, in 75% of the treated EAE rats monocyte ingress in CNS was observed
      in vivo by magnetic resonance imaging with the ultrasmall superparamagnetic iron
      oxide contrast agent. Our data shed new light on the role of remaining macrophage
      brain infiltration in an induced but interrupted T-cell-mediated EAE disease
      process.

PMID- 15471372
TI  - An fMRI study of planning-related brain activity in patients with moderately
      advanced multiple sclerosis.
AB  - INTRODUCTION: Cognitive impairment occurs in a substantial number of multiple
      sclerosis (MS) patients and often includes frontal lobe dysfunction. We used
      functional magnetic resonance imaging (fMRI) to study planning, an executive
      function, in moderately impaired MS patients. METHODS: An fMRI version of the
      Tower of London (ToL) test was used to study patterns of brain activation in 23
      MS patients and 18 healthy controls. The median score on the Expanded Disability
      Status Scale (EDSS) for the MS patients was 4. fMRI data were analysed using
      whole brain random effects analysis as well as region of interest (ROI)-based
      methods to assess group effects. Within the MS group, associations with
      behavioural data and measures of disease severity (lesion load from structural
      MRI) were examined. RESULTS: Test performance in MS patients was significantly
      worse than in controls. Group analysis for the MS patients and the controls
      showed for both groups globally the same areas of activation, located in the
      frontal and parietal lobes bilaterally and the cerebellum. Although visual
      inspection suggested a larger extent of activation in the MS group, no
      statistically significant differences between groups were found. In the ROI
      analysis, statistically significant larger extent of activation was only found in
      the cerebellum. No association between disease severity and brain activity could
      be determined in the MS group. CONCLUSION: In MS patients with moderate
      disability and structural damage, the pattern and extent of brain activation
      during planning were maintained despite poorer performance. In contrast to other
      studies showing increased activity, the failure to do so in our group may reflect
      exhaustion of adaptive mechanisms.

PMID- 15471373
TI  - T1 relaxation maps allow differentiation between pathologic tissue subsets in
      relapsing-remitting and secondary progressive multiple sclerosis.
AB  - In an attempt to clarify whether T1 relaxation time mapping may assist in
      characterizing the pathological brain tissue substrate of multiple sclerosis
      (MS), we compared the T1 relaxation times of lesions, areas of normal-appearing
      white matter (NAWM) located proximal to lesions, and areas of NAWM located
      distant from lesions in 12 patients with the relapsing-remitting and 12 with the
      secondary progressive (SP) subtype of disease. Nine healthy volunteers served as
      controls. Calculated mean T1 values were averaged across all patients within each
      clinical group, and comparisons were made by means of the Mann-Whitney U-test.
      Significant differences were found between all investigated brain regions within
      each clinical subgroup. Significant differences were also detected for each
      investigated brain region among clinical subgroups. While T1 values of NAWM were
      significantly higher in patients with SP disease than in normal white matter
      (NWM) of controls, no differences were detected when corresponding brain areas of
      patients with RR MS were compared with NWM of controls. T1 maps identify areas of
      the brain that are damaged to a different extent in patients with MS, and may be
      of help in monitoring disease progression.

PMID- 15471374
TI  - Frontal parenchymal atrophy measures in multiple sclerosis.
AB  - The aim of this study was to establish whether, in a cross-sectional study, the
      normalized measures of whole and regional brain atrophy correlate better with
      tests assessing the cognitive function than the absolute brain atrophy measures.
      The neuropsychological performances and disability have been assessed in 39
      patients with relapsing-remitting multiple sclerosis (MS). T1- and T2-lesion load
      (LL) of total brain and frontal lobes (FLs) were measured using a reproducible
      semiautomated technique. The whole brain volume and the regional brain
      parenchymal volume (RBPV) of FLs were obtained using a computerized interactive
      program, which incorporates semiautomated and automated segmentation processes.
      Normalized measures of brain atrophy, i.e., brain parenchymal fraction (BPF) and
      regional brain parenchymal fraction (RBPF) of FLs, were calculated. The scan
      rescan, inter- and intrarater coefficient of variation (COV) and intraclass
      correlation coefficient (ICC) have been estimated. The RBPF of FLs showed an
      acceptable level of reproducibility which ranged from 1.7% for intrarater
      variability to 3.2% for scan-rescan variability. The mean ICC was 0.88 (CI 0.82
      0.93). The RBPF of FLs demonstrated stronger magnitudes of correlation with
      neuropsychological functioning, disability and quantitative MRI lesion measures
      than RBPV. These differences were statistically significant: P<0.001 for Stroop
      Color Word Interference test, P<0.001 for Paced Auditory Serial Addition Test,
      P=0.04 for Standard Raven Progressive Matrices, P=0.049 for Expanded Disability
      Status Scale, P=0.01 for T2-LL of FLs and P<0.001 for T1-LL of FLs. BPF
      demonstrated significant correlations with tests assessing cognitive functions,
      whereas BPAV did not. The correlation analysis results were supported by the
      results of multiple regression analysis which showed that only the normalized
      brain atrophy measures were associated with tests exploring the cognitive
      functions. These data suggest that RBPF is a reproducible and sensitive method
      for measuring frontal parenchymal atrophy. The normalized measures of whole and
      regional brain parenchymal atrophy should be preferred to absolute measures in
      future studies that correlate neuropsychological performances and brain atrophy
      measures in patients with MS.

PMID- 15471375
TI  - Multiple Sclerosis Impact Scale (MSIS-29): relation to established measures of
      impairment and disability.
AB  - OBJECTIVE: To validate the newly developed Multiple Sclerosis Impact Scale (MSIS
      29) in a large, well characterized, independent group of MS patients by
      investigating the relation between the MSIS-29 and the Guy's Neurological
      Disability Scale (GNDS), the Expanded Disability Status Scale (EDSS) and the MS
      Functional Composite (MSFC). METHODS: Two hundred MS patients were recruited at
      our outpatient department. At the same visit GNDS, EDSS, MSFC and MSIS-29 were
      assessed. Data obtained from GNDS, EDSS and MSFC assessment were compared to both
      physical and psychological impact scores of the MSIS-29. In addition the
      contribution of GNDS subcategories, EDSS functional systems and MSFC components
      to the physical and psychological impact scores of the MSIS-29 was studied.
      RESULTS: Median scores were 37.5 for the physical and 22.2 for the psychological
      impact score of the MSIS-29, 13.0 for GNDS and 4.0 for EDSS. Mean MSFC was 0.07.
      The physical impact score showed good correlations with both GNDS (0.79) and EDSS
      (0.68) and a moderate correlation with the MSFC (-0.53). The psychological impact
      score showed weak correlations with EDSS (0.22) and MSFC (-0.30) and a moderately
      strong correlation with the GNDS (0.58). In 50 (25%) patients, scores on physical
      and psychological impact scales diverted, i.e., a relative high score on one
      scale combined with a relative low score on the other scale. This was related to
      the clinical disease course. CONCLUSION: Our study supports the use of the MSIS
      29 as a measure for the assessment of physical impact of MS on normal daily life.
      In addition, our data provides a deeper understanding of the factors that
      determine both physical and psychological disease impact. Discrepancies between
      the latter two aspects deserve further attention.

PMID- 15471376
TI  - A prospective study of conditions associated with multiple sclerosis in a cohort
      of 658 consecutive outpatients attending a multiple sclerosis clinic.
AB  - The cause of multiple sclerosis (MS) remains unknown. It is largely regarded as
      being an inflammatory autoimmune disease and has been reported in association
      with other inflammatory/autoimmune diseases. We performed a prospective study in
      658 consecutive patients diagnosed with MS attending our outpatient MS management
      clinic between June 2002 and June 2003. Prevalence of associated conditions in
      these patients was calculated and compared with values from population studies
      using chi-square tests, odds ratios and confidence intervals. The MS population
      had significantly increased rates of asthma, inflammatory bowel disease, type 1
      diabetes mellitus, pernicious anaemia, autoimmune thyroid disease, uveitis,
      seronegative spondyloarthropathies, bipolar disorder and melanoma compared to the
      general population. Both T helper type 1 (Th1)-mediated and T helper type 2 (Th2)
      mediated diseases were significantly increased compared to the general
      population. There were also interesting associations seen with polyglandular
      autoimmune syndrome and rare single case associations. MS is associated with
      several other conditions. This work does not give evidence for the hypothesis
      that MS and atopy, reflecting Th1 and Th2 polarization, respectively, are
      mutually exclusive. Further work, ideally with a matched control population, is
      indicated.

PMID- 15471377
TI  - Multiple sclerosis gender issues: clinical practices of women neurologists.
AB  - Substantially more women than men develop multiple sclerosis (MS), but
      information about the effects of MS and gender-specific issues such as pregnancy,
      breastfeeding, menstruation and hormone use is lacking. A survey study of
      neurologists' practice patterns was undertaken to elicit information about gender
      specific topics and the use of disease-modifying MS therapies (DMT) including the
      interferons and glatiramer acetate (GA). A total of 147 surveys were returned.
      Half of respondents require patients to discontinue DMT during pregnancy, while
      35% encourage discontinuation. Among those who allow patients to continue
      therapy, half consider GA to be safer during pregnancy than the interferons.
      Nearly 86% of respondents do not use DMT in patients who are breastfeeding. Among
      the 11% who actually prescribe during breastfeeding, most recommend GA.
      Neurologists generally leave the decision to breastfeed up to patients, and most
      refer patients to obstetrician/gynaecologists for counselling about contraception
      or hormone replacement therapy. The survey results described here provide insight
      into how neurologists manage reproductive health issues among women with MS.

PMID- 15471378
TI  - Prevalence and treatment of spasticity reported by multiple sclerosis patients.
AB  - The objective of this study was to characterize the population of multiple
      sclerosis (MS) patients suffering from spasticity and to evaluate treatment
      patterns, including intrathecal baclofen (ITB) delivery, related to patient
      quality of life (QOL). We conducted a cross-sectional, two-level study using data
      from the Patient Registry of the North American Research Committee on MS
      (NARCOMS). In addition, we surveyed a subgroup of 198 preselected patients who
      are using ITB (ITBG) and a random sample of 315 oral drug users (ORALG). Among
      the registrants, 16% reported no spasticity, 31% minimal, 19% mild, 17% moderate
      (frequently affects activities), 13% severe (daily forced to modify activities)
      and 4% total (prevents daily activities). Patients experiencing greater severity
      included by proportion males, and those older and with longer duration of MS. QOL
      scores decreased inversely with severity. In the focused survey, ITBG reported
      lower levels of spasticity than ORALG, less stiffness in the legs, less pain and
      fewer spasms at any time. They scored significantly lower in the SF-36 physical
      component, yet reported less fatigue on the MFIS scale. Prevalence data reveal
      that one third of MS patients modify or eliminate daily activities as a result of
      spasticity. Treatment of spasticity can significantly impact QOL parameters by
      reducing spasms, pain and fatigue.

PMID- 15471379
TI  - Intravenous corticosteroids in the postpartum period for reduction of acute
      exacerbations in multiple sclerosis.
AB  - In order to assess the effectiveness of monthly intravenous corticosteroids in
      reducing childbirth-associated acute exacerbations in multiple sclerosis (MS), we
      compared pregnant patients followed up in our MS clinic. During the first period
      (1996-1998), 22 patients did not receive any treatment after delivery. During the
      second period (1999-2001), following the publication of the PRIMS study, 20
      patients were treated monthly with 1 g of intravenous corticosteroids during the
      six months of the postpartum period. In both groups the relapse rate increased
      during the first trimester postpartum but it was higher in the untreated group
      (2+/-0.66 [mean+/-SD]) compared with the treated group (0.8+/-0.41) (P=0.018),
      suggesting a beneficial effect of monthly intravenous corticosteroids.

PMID- 15471380
TI  - Waldenstrom's macroglobulinemia developing in a patient with multiple sclerosis:
      coincidence or association?
AB  - Multiple sclerosis (MS) has been reported in association with haematological
      abnormalities, including monoclonal gammopathies. We present a 54-year-old male
      patient with a 30-year history of MS who was admitted to our hospital for
      investigation of anaemia and increased erythrocyte sedimentation rate. A
      monoclonal IgM protein was detected by serum protein immunofixation, while bone
      marrow biopsy indicated a 70% infiltration by small lymphoplasmacytoid cells, in
      the context of a lymphoplasmacytoid immunocytoma, findings compatible to the
      diagnosis of Waldenstrom's macroglobulinemia (WM). To our knowledge, this is the
      first report of WM in a patient with MS. Further to the coexistence of the two
      diseases observed in the case presented here, there is additional evidence
      suggesting that the association of MS with plasma cell dyscrasias may not be
      coincidental.

PMID- 15471381
TI  - Anxiety sensitivity: association with intensity of retrospectively-rated smoking
      related withdrawal symptoms and motivation to quit.
AB  - The present cross-sectional study evaluated the associations between anxiety
      sensitivity, intensity of retrospectively-rated nicotine withdrawal symptoms, and
      motivation to quit smoking. Participants were 127 young adult (mean age 20.4
      years (SD 4.6)) regular smokers (mean cigarettes per day 10.2 (SD 5.1)). Anxiety
      sensitivity predicted intensity of retrospectively rated withdrawal symptoms
      during the first week of the most recent quit attempt as well as concurrent and
      lifetime indices of motivation to quit smoking even after controlling for
      theoretically-relevant smoking (e.g. nicotine dependence) and affect (e.g. panic
      attack history) factors. These results are discussed in relation to better
      understanding panic-related vulnerability factors in smoking cessation.

PMID- 15471382
TI  - Non-specific encoding of threat in social phobia and panic disorder.
AB  - This study employs a release of proactive interference technique to explore
      encoding-related processes in social phobia. Twenty-six individuals with social
      phobia and 24 individuals with panic disorder participated in the memory task.
      Significant release of proactive interference was found when neutral and threat
      dimensions were encoded, but not when social and physical threat dimensions, or
      when positive and threat dimensions were presented. Threat was therefore
      differently encoded depending on the active encoding context in which semantic
      processing occurred. Individuals with social phobia or panic disorder did not
      differ in the release of proactive interference. The present experiment
      consequently yields little support for the specificity hypothesis in memory of
      anxious individuals. Instead, the findings generally demonstrate that threat
      encoding is similar for people with social phobia and those with panic disorder.

PMID- 15471383
TI  - A microswitch program to foster simple foot and leg movements in adult wheelchair
      users with multiple disabilities.
AB  - This study assessed a microswitch program to foster simple foot and leg movements
      in 2 adult wheelchair users with multiple disabilities. The participants' mood
      (indices of happiness) was recorded throughout the study. Data showed that
      participants rapidly increased the target foot and leg movements and maintained
      those movements during the course of the study, which lasted about 4.5 months.
      With regard to indices of happiness, 1 participant showed a fairly modest
      increase during the intervention while the other participant showed a substantial
      increase. Implications of the findings are discussed.

PMID- 15471384
TI  - Manual-based cognitive behaviour therapy for chronic fatigue syndrome:
      therapists' adherence and perceptions.
AB  - Several randomized controlled trials have indicated that cognitive behaviour
      therapy is an effective treatment for chronic fatigue syndrome. In 1 of these
      studies 13 therapists applied cognitive behaviour therapy for chronic fatigue
      syndrome in 83 chronic fatigue syndrome patients. In the present study
      therapists' adherence and perceptions of the manual are studied. Following
      completion of the study the therapists were asked to complete a questionnaire.
      Audiotaped sessions were conducted to verify the therapists' adherence. Analyses
      of the audiotapes showed that in 87% of the sessions this appeared to be the
      case. The questionnaire revealed that the therapists found it more difficult to
      treat patients with chronic fatigue syndrome than to treat patients with
      psychological or other physical problems. Treatment aspects posing the most
      problems were integrating individual problems into the standardized treatment,
      dealing with the patients' lack of confidence in the treatment and handling
      insufficient motivation.

PMID- 15471385
TI  - The relationship between interpersonal perception and post-traumatic stress
      disorder-related functional impairment: a social relations model analysis.
AB  - This study used Kenny's social relations model to examine the relationship
      between Post-Traumatic Stress Disorder-related impairment and interpersonal
      perceptions. Participants were 124 students who had previously completed the Post
      traumatic Stress Diagnostic Scale as part of a larger study. After engaging in
      brief dyadic conversations with 3 other students, participants recorded
      perceptions of personality traits for themselves, their interaction partners and
      how they believed their partners saw them (metaperceptions). Results indicated
      that those with more severe post-traumatic stress disorder-related impairment saw
      themselves negatively and believed their interaction partners also viewed them
      negatively. However, these individuals were not seen differently by others,
      except that they were rated as less dependable. Our findings suggest that post
      traumatic stress disorder is associated with negative beliefs about the self that
      may influence self-esteem and interpersonal relationships.

PMID- 15471386
TI  - [Cybernetics in cardiology (yesterday, today, tomorrow)].

PMID- 15471387
TI  - [Experimental and clinical assessment of antioxidant efficacy of multicomponent
      antioxidant medication].
AB  - AIM: To study an antioxidant action of antioxidant vitamins (vitamins C, E and
      provitamin A) in vitro and in vivo. MATERIAL AND METHODS: The study was made of
      kinetic parameters of copper-initiated free radical oxidation (FRO) of low
      density lipoproteins (HDLP) in human blood plasm, antioxidant potential of rat
      liver and myocardium, the level of FRO products in HDLP and activity of
      glutathione peroxidase in erythrocytes of 31 males aged 40-64 years with coronary
      heart disease (CHD). RESULTS: An antioxidant action of the combinations alpha
      tocopherol+ascorbic acid and alpha-tocopherol+beta-carotin was much more potent
      than that of each of the component alone. The whole complex of the antioxidants
      completely suppressed FRO of HDLP in the model system. Feeding rats for 30 days
      with a complex of antioxidant vitamins and selenium produced a sharp enhancement
      of the antioxidant potential of the liver and a complete suppression of free
      radical processes in the myocardium. If this complex was given to CHD patients
      for 2 months, it sharply reduced the amount of FRO primary and secondary products
      in blood plasm LDLP in growing activity of erythrocytic selenium-containing
      glutathione peroxidase. CONCLUSION: The scheme is proposed for objective
      experimental assessment of antioxidant efficacy of multicomponent antioxidant
      medication in laboratory and clinical trials.

PMID- 15471388
TI  - [Efficacy and safety of hydrogen sulfide balneotherapy in ischemic heart disease
      the arid zone].
AB  - AIM: To evaluate efficacy of hydrogen sulfide (HS) balneotherapy in patients with
      coronary heart disease (CHD) in conditions of heat discomfort. MATERIAL AND
      METHODS: The study included 72 CHD patients aged 35 to 60 years with stable
      angina pectoris of the second functional class taking balneotherapy in summer
      under arid climatic conditions. Before and after balneotherapy the patients were
      examined with estimation of clinical symptoms, stress bicycle exercise (SBE)
      parameters, number of nitroglycerine tablets. RESULTS: The balneotherapy resulted
      in a significant prolongation of SBE (p < 0.0018), in longer time to depression
      of the ST segment by 1 mm (p < 0.01), to an anginal attack in the course of SBE
      (p < 0.0036), shorter duration of pain after SBE (p < 0.001), less number of
      anginal attacks (p < 0.0002) and reduced need in short-acting nitrates (p <
      0.0002). CONCLUSION: In a hot climate of the arid zone use of moderate HS baths
      raises tolerance of CHD patients to exercise, attenuates clinical manifestations
      of CHD and, consequently, reduces daily need in nitrates.

PMID- 15471389
TI  - [Dysaggregants effect of platelet aggregation in patients with non-ST segment
      elevation acute coronary syndrome].
AB  - AIM: To study efficacy of treating patients with acute coronary syndrome (ACS)
      without ST segment elevation (STSE) with platelet dysaggregation drugs (aspirin,
      cardiomagnil, clopidogrel). MATERIAL AND METHODS: 78 ACS without STSE were
      randomized into five groups: group 1 patients (n = 17) received no dysaggregants;
      patients of group 2 (n = 26) received aspirin in the dose 250 mg on the day of
      admission and then 125 mg/day; group 3 was given cardiomagnil (150 mg on the day
      of admission and then 75 mg/day, n = 17); group 4--clopidogrel 75 mg/day (n = 7);
      group 5--combination of clopidogrel 75 mg/day with cardiomagnil 75 mg/day (n =
      11). All the patients were administered fraxiparin 86 IU/kg sc each 12 hours for
      5-8 days. RESULTS: Group 1 patients showed platelet hyperaggregation, platelet
      aggregation decreased in groups 2, 3 and 4 (6 patients of group 1 were resistant
      to aspirin). The highest antiaggregation effect was achieved in group 5.
      CONCLUSION: Control over antiaggregation treatment in patients with ACS without
      STSE by monitoring of platelet function open broad opportunities for selection of
      effective individual therapy.

PMID- 15471390
TI  - [Effect of long-term epidural analgesia and nitroglycerin infusion on formation
      of necrosis zone and clinical course of myocardial infarction].
AB  - AIM: To study effects of long-term morphine-clofelin epidural analgesia and
      infusion of nitroglycerin on formation of the necrosis focus and the clinical
      course of acute myocardial infarction (MI). MATERIAL AND METHODS: Ninety patients
      were examined within the first 12 hours of anterior macrofocal MI. Forty six
      patients of the study group received long-term morphine-clofelin epidural
      analgesia and nitroglycerine infusion within the first 24 hours of the disease.
      Forty-four control patients were anesthetized conventionally with intravenous
      morphine. Development of MI was assessed with electrocardiotopography and dynamic
      examination of MV CK in the blood serum. RESULTS: The degree and area of the
      myocardial lesion were initially similar in the study and control groups. These
      indices were less in dynamics in the study group. On MI day 5 and 10 myocardial
      necrosis zone significantly diminished in the study group. CONCLUSION: Long-term
      epidural analgesia and nitroglycerin infusion provide effective analgesia,
      localizes the ischemic and necrotic focus, have a good effect on hemodynamics and
      improve a MI clinical course.

PMID- 15471391
TI  - [A course of coronary heart disease and quality of life in patients with varying
      depressive states].
AB  - AIM: To study a course of coronary heart disease (CHD) in patients with
      depressive disorders. MATERIAL AND METHODS: The trial included 77 CHD patients
      aged 39 to 68 years (mean age 54.9 +/- 0.9 years), 40 (51.9%) of them had
      myocardial infarction. All the examinees had effort angina of functional class II
      IV by criteria of the Canadian Cardiology Association. All the patients have
      undergone standard clinical examination, stress tests, coronaroangiography (n =
      30), assessment of the degree of vegetative dystonia and quality of life. The
      patients were divided into two groups depending on the depression degree.
      RESULTS: CHD patients with manifest depression vs those with subclinical
      depression had a higher level of personality and reactive anxiety. They had
      neurotic and psychopathological personality alterations associated with more
      pronounced vegetative disorders. These patients suffered from more severe
      coronary atherosclerosis, more hospitalizations for the previous year, more
      myocardial infarctions, lower physical activity and quality of life. CONCLUSION:
      CHD patients with manifest depression have lower physical performance and quality
      of life though this is not confirmed at exercise tests.

PMID- 15471392
TI  - [Thiaside diuretics in combination with inhibitors of angiotensin-converting
      enzyme in patients with diabetes mellitus type 2 comorbid with arterial
      hypertension].
AB  - AIM: To study the effect of co-renitek monotherapy for 16 weeks on parameters of
      24-h monitoring of arterial pressure, carbohydrate, lipid, purin metabolism in
      patients with mild and moderate arterial hypertension (AH) and diabetes mellitus
      (DM) type 2. MATERIAL AND METHODS: 20 patients with DM type 2, mild or moderate
      AH received co-renitek (1-2 tablets a day) for 16 weeks. Before the treatment and
      16 weeks later the patients were examined (24-h AH monitoring, carbohydrate,
      lipid, purin, electrolyte metabolism). RESULTS: Co-renitek treatment of DM type 2
      patients with hypertension led to a significant lowering of mean systolic and
      diastolic pressure, improvement of 24-h AP profile and reduction of fasting
      glucose level. Co-renitek proved to be metabolically neutral in relation to
      lipid, purin and electrolyte metabolism. CONCLUSION: Co-renitek is effective and
      safe antihypertensive drug for treatment of arterial hypertension in patients
      with diabetes mellitus type 2.

PMID- 15471393
TI  - [Propranolol treatment of effort angina in patients with arterial hypotension].
AB  - AIM: To compare antianginal efficacy and tolerability of propranolol therapy in
      patients with stable angina pectoris and chronic hypotension (Hpts) and
      normotensive patients with angina of effort (Npts). MATERIAL AND METHODS: A
      randomized, single-blind, placebo-controlled study was made in 35 Hpts and 38
      Npts was made using bicycle exercise tests, echocardiography, stress myocardial
      scintigraphy with 77-199. RESULTS: Acute bicycle exercise tests showed high anti
      ischemic activity of propranolol in 86% Hpts and 65% Npts. Stable antianginal
      propranolol effect in 57% Hpts was accompanied with a decrease of myocardial
      perfusion defect. Secondary resistance or pseudotolerance to an antianginal
      effect of propranolol was observed in 43% Hpts in 4-12 weeks (vs 0 of Npts; p <
      0.01) as evidenced by T-199 stress myocardial scintigraphy. Hpts with secondary
      resistance and pseudotolerance to propranolol had lower control hypotension and
      bradicardia (p < 0.05), more anginal attacks (p < 0.001). CONCLUSION: Hpts had
      rapidly developing secondary resistance and pseudotolerance to propranolol
      antianginal effect, bad tolerability of the drug.

PMID- 15471394
TI  - [Structure of the sinus dysfunction in hypertensive patients].

PMID- 15471395
TI  - [Results of midodrin treatment of vasovagal syncope].
AB  - AIM: To elicit efficacy of midodrin in patients with vasovagal syncope. MATERIAL
      AND METHODS: 50 patients with recurrent vasovagal syncope documented by head-up
      tilt tests or bicycle exercise stress tests participated in the study. These
      tests controlled the effects of midodrin if syncopes occurred again in repetition
      of the tests. In the other patients the effect of the drug was assessed
      clinically. All the patients received midodrin in daily dose up to 15 mg.
      RESULTS: Mirodrin effectively prevented syncope in 13 (72%) patients as shown by
      the tilt test, in 10 (59%) patients as shown by the exercise stress tests and in
      14 (93%) patients as controlled clinically. Total efficacy of midodrin was 74%
      (37 of 50 patients). CONCLUSION: Midodrin demonstrated high efficacy in
      prevention of vasovagal syncope. Side effects were not serious therefore the drug
      is well tolerated.

PMID- 15471396
TI  - [How to manage patients with atrial fibrillation in a general hospital].
AB  - AIM: To evaluate efficacy of use of technological charts (TC) in upgrading
      management and treatment safety in patients with atrial fibrillation (AF).
      MATERIAL AND METHODS: Two groups of AF patients were compared: 196 patients
      treated before introduction of TC (group 1) and 431 patients managed according to
      TC technology (group 2). RESULTS: In group 2 treatment duration reduced from 26.1
      to 18.5 days, rehospitalizations occurred by 6% less frequently, number of
      unexpected side effects fell 2.5-fold, the rate of varfarin prescription for
      prevention of thromboembolic complications rose from 18 to 64%, the patients were
      satisfied with the treatment in 97% vs past 79%. CONCLUSION: TC was a tool of
      treatment improvement and introduction of the latest clinical recommendations
      into clinical practice with reference to facilities and staff qualification of an
      individual hospital without additional financial input.

PMID- 15471397
TI  - [Effective control of a severe exacerbation of bronchial asthma].
AB  - AIM: To evaluate effectiveness and safety of nebulizer therapy (NT) with
      broncholytics and pulmicort suspension (PS) in patients with a severe
      exacerbation of bronchial asthma (BA). MATERIAL AND METHODS: 75 patients with a
      severe BA exacerbation received broncholytic NT with consideration of comorbid
      pathology and age. Nebulized PS was used as an alternative to systemic
      glucocorticosteroids (SGCS). NT efficacy was assessed by changes in clinical
      symptoms, in the peak expiration velocity (PEV) and spirometry parameters. Safety
      was controlled by 24-h ECG monitoring, pulsoximetry. PS was examined for effect
      on adrenal cortex, calcium metabolism, oral infection with Candida. Side effects
      were registered. RESULTS: Clinical improvement was recorded in all the patients.
      NT reduced the number of additional inhalations of short-acting beta2-agonists 4
      5 times, on the average. In the end of NT there was a 4.66% increase in SaO2 vs
      the initial value (p = 0.04). PEV and FEV1 increased. Plasm levels of
      hydrocortisone and its urine excretion did not lower vs initial values.
      CONCLUSION: The results of the study point to efficacy and safety of combined NT
      with broncholytics and PS in a severe exacerbation of BA.

PMID- 15471398
TI  - [Efficacy of a complementary antiinflammatory treatment with erespal in chronic
      obstructive and nonobstructive bronchitis].
AB  - AIM: To compare efficacy of atrovent alone and in combination with erespal in
      patients with chronic bronchitis (CB) and chronic obstructive pulmonary disease
      (COPD). MATERIAL AND METHODS: Of 80 participants of the trial (51 male and 29
      female--63.75 and 36.25%, respectively) who had CB or COPD, 39 patients (28 with
      CB and 11 with COPD) received 6-month combined treatment with erespal (160
      mg/day) and atrovent (160 mcg/day) and 41 patients (32 with CB and 9 with COPD)
      received atrovent monotherapy in the same dosage. RESULTS: Combined therapy
      produced positive changes in dyspnea, sputum characteristics and its discharge,
      cough, monotherapy improved sputum discharge and relieved cough; pulmonary
      ventilation improved in both groups especially in those on monotherapy. CB
      patients showed low cytosis, percentage and absolute count of neutrophils,
      absolute count of lymphocytes and eosinophils in induced sputum. In CB patients
      percentage of lymphocytes reduced while count of macrophages went up. Combined
      treatment including erespal also promoted a significant fall of serum and sputum
      TNFalpha and IL-8 reduction in the sputum. CONCLUSION: Erespal+atrovent treatment
      proved more effective than atrovent alone. It is recommended for both CB and COPD
      patients without marked disorders of external respiration function.

PMID- 15471399
TI  - [Vasaprostan treatment of fibrosing alveolitis in patients with pulmonary
      hypertension].
AB  - AIM: To study clinical efficacy of vasaprostan in patients with fibrosing
      alveolitis (FA) complicated by pulmonary hypertension (PH), its effect on
      functional activity of platelets and endothelium, intensity of free radical
      processes. MATERIAL AND METHODS: Seven FA patients were examined. They had either
      idiopathic FA or FA with diffuse diseases of the connective tissues. The
      following methods were used to assess the effect: standard clinical tests, high
      resolution computer tomography, Doppler echocardiography, definition of the
      complex thrombin-antithrombin (TAT) and thrombocytic factor 4 (TF-4). Generation
      of oxygen active forms by leukocytes was measured by luminol-dependent
      chemiluminescence. Morphological verification of the diagnosis was made by the
      results of open pulmonary biopsies. RESULTS: Vasaprostan reduced pressure in the
      pulmonary artery from 31.6 +/- 2.31 to 19.58 +/- 3.90 mm Hg (p < 0.05) and
      coagulation parameters. TAT decreased after 2 and 8 weeks of treatment from 15.25
      +/- 4.5 to 5.1 +/- 0.33 and 2.4 +/- 0.31 pg/ml (p < 0.05). Initially low TF-4
      (2.11 +/- 0.39 pg/ml) elevated to the end of the treatment and reached values
      close to control (4.37 +/- 0.25 pg/ml, p < 0.05). Moreover, vasaprostan enhanced
      the ability of platelets to inhibit generation of active oxygen forms (from 0.9
      +/- 0.18 to 1.23 +/- 0.16 r. u., p < 0.05) and thus depressed activity of lipid
      peroxidation. CONCLUSION: Good effect of vasaprostan on platelet activity, free
      radical processes validates its use in combined treatment of various FA forms for
      correction of PH, its complications and as an antifibrogenic agent.

PMID- 15471400
TI  - [Prognostic implications of mixed monoclonal cryoglobulinemia in Sjogren's
      disease].
AB  - AIM: To specify the risk of severe systemic manifestations and transformation
      into malignant lymphoma in Sjogren's disease (SD) patients with monoclonal mixed
      cryoglobulinemia (MMC). MATERIAL AND METHODS: A prospective study performed in
      1985-1990 included 248 SD patients followed up after the initial detection of
      monoclonal immunoglobulins (Ig) with serum active rheumatoid factor (RF). The
      patients' cryoglobulins (CG) were examined. The type of CG was determined by
      electrophoresis in agarose gel combined with immunofixation and
      immunoelectrophoresis with mono-specific antisera to heavy and light Ig chains.
      Biopsies of the lower lip salivary glands and skin were made in all the patients
      with MMC and 40 patients without CG. The biopsies were studied histologically,
      histochemically and immunomorphologically. Clinical symptoms and prognosis were
      studied in all the patients observed in 1985-2000 after the initial diagnosis of
      MMC. In suspected lymphoma development, histological and immunophenotypical
      studies of lymph node, bone marrow biopsies, trephine biopsies were made as well
      as myelograms, Ga-67 scintigraphy, CT of the thoracic and abdominal cavities. The
      total of clinical, morphological, immunophenotypical and cytogenetic
      characteristics of lymphoma was estimated by REAL classification. RESULTS: CG at
      first examination was detected in 50 (20.2%) of 248 patients with SD. 20 (40%) of
      50 patients were diagnosed to have MMC with monoclonal IgMchi (19) and IgA (1) in
      the serum with RF activity. Ten (50%) patients with MMC developed lymphoma after
      10.9 +/- 3.3 years, on the average. In the absence of CG lymphoma developed in
      5.5% (p < 0.001). B-cell intoxication in patients with diffuse lymphadenopathy,
      foci of lymphoid infiltration in the lungs, ulcers of the crus and such indices
      as stab neutrophilic shift, monocytosis, hypoproteinemia with
      hypogammaglobulinemia, disappearance of the RF, CG, low CIC level,
      immunodeficiency of monoclonal Ig and appearance of the protein BJ in the urine
      are markers of developing large B-cell immunosecreting lymphomas. Highly
      aggressive diffuse LCL resulted in death of 70% SD patients with MMC; 30% died of
      immunocomplex cryoglobulinemic vasculitis. 10-15-year survival of SD patients
      after detection of MMC was 50%, free of CG - 97% (p < 0.001). CONCLUSION: MMC is
      a definite serological marker of developing lymphoma and ulcerative-necrotic
      vasculitis in SD. In detection of MMC in SD patients it is necessary to prescribe
      early pathogenetically validated treatment before development of life threatening
      manifestations.

PMID- 15471401
TI  - [Structum in combined treatment of low back pain syndrome].
AB  - AIM: To assess duration of a clinical response and tolerance of structum in
      patients with low back pain (LBP) and comorbid cardiovascular disease. MATERIAL
      AND METHODS: 25 patients with primary LBP and coronary heart disease (n = 13)
      and/or essential arterial hypertension (n = 18) were examined and treated for 6
      months with structum. RESULTS: To the end of the first treatment months structum
      significantly relieved pain intensity, spinal motility, increased exercise
      tolerance. Excellent and good response to structum were observed in 71% patients,
      no response was in 29%. Tolerance of the drug was good in 23 (92%) patients. The
      effect persisted for 3 months. CHD characteristics did not change while arterial
      pressure went down noticiably. CONCLUSION: Structum is highly effective in the
      treatment of LBP. Its long-term intake had no effect on CHD.

PMID- 15471402
TI  - [Effects of interferonotherapy on functional activity of platelets in chronic
      viral hepatitis and cirrhosis of the liver].
AB  - AIM: To characterize effects of interferon alpha (If-a) on functional activity of
      platelets in patients with chronic viral hepatitis (CVH) and viral hepatic
      cirrhosis (VHC). MATERIAL AND METHODS: Induced platelet aggregation (PA),
      spontaneous PA, levels of cAMP, cGMP and glycogen in platelets, plasm beta
      thromboglobulin (bTG) and activity of thrombocytic factor 4 (TF4) were measured
      in 95 patients before, 4.5 h after the first If-a introduction, after 12 and 24
      weeks of If-a treatment. RESULTS: The patients demonstrated low induced PA,
      intracellular glycogen and high cAMP, b-TG and TF4. The initial administration of
      If-a led to normalization of most of functional platelet indices. A 24-h course
      of If-a therapy normalized platelet functions irrespective of stability of the
      virusological response. CONCLUSION: If-a preparations in single and multiple
      administrations normalize platelet function.

PMID- 15471404
TI  - [Efficacy of low-intensive laser irradiation in coronary heart disease].

PMID- 15471403
TI  - [Ways of modification of food fats in antiatherogenic diet].

PMID- 15471406
TI  - [Thrombotic thrombocytopenic purpura: diagnosis and treatment].

PMID- 15471405
TI  - [The problem of preventing vascular restenosis after implantation of a coronary
      stent].

PMID- 15471407
TI  - [History of the studies of senile aortic stenosis (the 100th anniversary of I.
      Munkeberg's publication)].

PMID- 15471408
TI  - [Methodological aspects of organizational and organizational-and-staff structure
      planning for military medical units and institutions].

PMID- 15471409
TI  - [Informative technologies used in laboratory department of the field medical
      institution of Russian military contingent in Kosovo].

PMID- 15471410
TI  - [Modern ideas concerning the mechanisms of gunshot injury formation
      (Communication 1)].
AB  - The affect of gunshot small arms depends on the weight, speed and moment of
      projectile's inertia, which determine the trajectory of its movement in the
      object's substance and the degree of braking characterizing the fullness of
      energy transmission. The experimental investigations on animals show that the
      mechanism of tissue lesion during the gunshot injuries has a very complex
      character and includes both the projectile's direct effect and initiation of some
      physical phenomena leading to significant tissue damage distally from the wound
      canal.

PMID- 15471411
TI  - [Change in carbohydrate metabolism during the acute period of traumatic disease].

PMID- 15471412
TI  - [Psychophysiologic characteristic of drafted servicemen with respiratory
      diseases].

PMID- 15471413
TI  - [The trace element status in patients with chronic hepatic diseases].
AB  - Despite of the achievements of pharmacology it is very actually to improve the
      diagnosis and therapy of different chronic hepatic diseases. The purpose of the
      investigation is to study trace element (TE) status in patients with chronic
      hepatic diseases for estimating the possibility of therapy efficiency
      improvement. 102 patients with chronic hepatic diseases, aged from 19 to 60 were
      clinically and laboratory investigated. Group 1 (36 patients) suffered from
      alcoholic liver cirrhosis, group 2 (35 patients) had chronic alcoholic
      steatohepatitis and group 3 (31 patients) had non-alcoholic steatohepatitis
      (NASH). Multielement blood plasma analysis by ICP-MS and ICP-OES was perfomed in
      the Center of Biotic Medicine (Moscow). The results showed the significant
      changes in TE status in patients with chronic hepatic diseases that proves the
      expediency of studying both the essential and toxic element in such patients to
      improve the diagnosis and to optimize the treatment. Patients with chronic
      hepatic diseases are characterized by changing of such elements as Al, Ca, Cu, K,
      Se, Zn, that leads to necessity of using them for diagnosis.

PMID- 15471414
TI  - [The problem of external therapy used in skin mycosis].

PMID- 15471415
TI  - [Diagnosis of Rickettsia prowazekii disease at the final stage of its
      elimination].
AB  - Diagnosis of Rickettsia prowazekii forms at the final stage of its elimination.
      30 cases of petechial typhus occurred in Russian Federation during the period
      from 1973 to 1996 were subjected to retrospective analysis. On the base of this
      analysis the false registration of disease "epidemic" form was revealed. Indeed
      it appeared to be the recurrences, i.e. the Brill's disease. The authors propose
      to use the table of differential diagnostic signs of both forms of Rickettsia
      prowazekii based on their clinical-and-epidemiological special features. It will
      help to avoid the false reports.

PMID- 15471416
TI  - [Metabolic and functional changes in a submariner body during long-term exposure
      to the factors of a controlled environment].

PMID- 15471417
TI  - [The emblems of military medicine].

PMID- 15471418
TI  - [Eisk military aviation hospital is 60 years].

PMID- 15471419
TI  - A third world international health elective for U.S. medical students: the 25
      year experience of the State University of New York, Downstate Medical Center.
AB  - The Department of Preventive Medicine and Community Health at the State
      University of New York, Downstate Medical Center instituted a 6-8 weeks third
      world international health elective for fourth year medical students in 1980.
      Since that time, some 217 students have participated in a score of third world
      countries. However, the most popular sites have been India, Kenya and Thailand.
      The purposes of this elective are to provide fourth year medical students with an
      opportunity to observe and study the structure and functions of a health care
      delivery system in a third world country, to provide medical service, and to have
      a cross-cultural experience. The emphasis in this elective is on public health,
      preventive medicine and primary care. There are high levels of student
      competition for this elective. However, interest in it has been affected by world
      events such as the terrorist attacks of September 11, 2001 and the recent
      outbreak of Severe Acute Respiratory Syndrome (SARS) in Asia. Recent annual
      applications for this elective have been twenty-five and more out of a class of
      two hundred students. Annual acceptance rates vary considerably, ranging from as
      low as 27.2% in 1995-1996 to a high of 81.8% in 1987-1988. Careful screening,
      including an examination of academic records and personal interviews, has
      resulted in the selection of highly mature, adaptable, and dedicated students who
      overall have performed well at overseas sites. Student rated satisfaction levels
      with this elective are extremely high, with most rating it the best experience of
      their medical school years. Students undergo extensive preparation prior to going
      overseas. This includes individual health and safety issues, travel and lodging,
      and the nature of the host country culture, health care system, and assignment
      site. Our students are especially experienced in cross-cultural understanding
      because of the unusual diversity of the patients they treat in Brooklyn, and the
      ethnic diversity of local hospital staff and the medical school class. This
      Brooklyn experience in cross-cultural understanding has been cited by many
      participants as having been the best preparation for functioning in a foreign
      culture. In the late 1990s, we revised our procedures concerning health
      preparations so as to address the risk of HIV/AIDS and other blood borne
      diseases. In addition, we also adopted an Agreement and Release form containing
      15 provisions requiring risk and responsibility assumption on the part of the
      student participants. The Alumni Fund of the College of Medicine has steadfastly
      supported this elective with both a philosophical commitment and financial grants
      to help defray travel costs. In 1998, Joshua H. Weiner of the class of 1941
      created a sizeable endowment in the Alumni Fund of the College of Medicine to
      support students participating in this elective. In 2001, Sonja K. Binkhorst,
      Assistant Professor of Psychiatry at the Downstate Medical Center, arranged for
      some financial support for women medical students through the LSK Foundation and
      the American Medical Women's Association. During the years that this elective has
      been offered, overseas preceptors have willingly given of their time and
      institutional resources to make these experiences available and meaningful for
      students.

PMID- 15471420
TI  - Strategies to increase smoke alarm use in high-risk households.
AB  - A 3-year project was undertaken to evaluate two methods of promoting residential
      smoke alarm installation and maintenance in high risk households across the U.S.
      Five states (Arkansas, Maine, Maryland, Massachusetts, and North Carolina)
      participated. The two strategies under study were direct installation of smoke
      alarms and distribution of a voucher for free smoke alarms. The target population
      included occupants of high-risk households without working smoke alarms who were
      approached as part of a door-to-door canvassing program. Fire Safety education
      was provided to both groups. A follow up assessment conducted 6-12 months post
      intervention assessed the presence and functional status of smoke alarms in each
      of the two groups. Demographic and fire safety data were also collected at
      baseline and follow up for each group. 4,455 households were enrolled in the
      study [Installation Group: 2,206 (49.5%), Voucher Group: 2,249 (50.5%)]. Baseline
      characteristics of the groups within each state were comparable. Follow up data
      was obtained on 1,583 installation group households and 1,545 voucher group
      households. At follow up, 1,421 (89.8%) households in the installation group had
      working smoke alarms, compared with 997 (65%) households in the voucher group,
      Odds Ratio 4.82 (95% CI=3.97, 5.85) (p <.0001). On average, 47% of all households
      enrolled in the voucher group did not redeem their vouchers (range 26-63%).
      Direct installation of alarms by program staff resulted in working smoke alarms
      in 90% of households receiving the direct installation intervention. Only 65% of
      voucher households had functioning alarms at follow up, largely due to failure to
      redeem vouchers.

PMID- 15471421
TI  - Are household factors putting immigrant Hispanic children at risk of becoming
      overweight: a community-based study in eastern North Carolina.
AB  - North Carolina has one of the fastest growing populations of Hispanic immigrants
      in the U.S. The prevalence of overweight among Hispanic children in the state has
      increased to 17%. Therefore, the objectives of this descriptive, exploratory
      study were to identify potential risk factors for childhood overweight at the
      household level among 128 immigrant Hispanic families with school-aged children
      living in Eastern North Carolina. Data concerning parental beliefs about
      overweight children, family participation in physical activity, and household
      availability of higher-calorie foods were collected using a structured, close
      ended interview form. Forty-seven percent of parents believed that overweight
      children are unhealthy, 11% that if a child is overweight, it is God's will, and
      over 90% believed that overweight children should be taken to a nutritionist or
      physician for help with weight reduction. The activities undertaken by families
      four to seven times per week were watching television (70%), listening to music
      (69%), and reading (61%). Cookies, cold cereals, crackers, whole milk, ice cream,
      cheese, hotdogs, peanut butter, soft drinks, fruit drinks, chips, and pudding
      were regularly available in a majority of households. Regression analysis
      indicated that household income, parental education, and rural versus urban
      residence had no significant impact on frequency of family participation in
      physical activity or household availability of higher-calorie foods. Findings
      suggest a need for bilingual community health professionals to develop culturally
      sensitive wellness programs targeted at immigrant Hispanic families that promote
      greater engagement in moderate-intensity physical activity and more frequent
      consumption of lower-calorie foods.

PMID- 15471422
TI  - Heart disease awareness among college students.
AB  - The purpose of this research was to explore college students' attitudes about
      heart disease risks and preventive strategies. The survey population consisted of
      students enrolled in selected lecture courses at Arizona State University. A
      total of 1481 surveys were used in data analysis. Respondents indicated a lower
      perception of heart disease risk for women than for men, and a majority of
      students incorrectly believed that breast cancer is a more significant health
      concern for women than heart disease. Respondents in most ethnic groups believed
      that whites are most at risk for developing heart disease. Students overall had
      relatively low levels of knowledge about heart disease and its risk factors
      compared to other health issues, such as sexually transmitted diseases (STDs) and
      psychological disorders. The results suggest that educational intervention is
      necessary to increase college students' knowledge about heart disease; and, in
      particular, efforts need to be made to raise awareness about heart disease among
      women and minorities. Guidelines for future educational intervention must address
      common misconceptions about which demographic groups are at risk for developing
      heart disease and address gaps in knowledge that young people have regarding
      heart disease prevention.

PMID- 15471423
TI  - Understanding barriers to implementing quality lunch and nutrition education.
AB  - Food services and nutrition education are priorities for the Coordinated School
      Health Program in Massachusetts, which is a CDC funded partnership between the
      Massachusetts Departments of Education and Public Health. Despite funding and
      resources provided by governmental and non-governmental agencies, schools are
      facing barriers in effectively creating a healthy nutritional environment. A
      qualitative survey was conducted to understand barriers to implementing quality
      lunch and nutrition education programs perceived by superintendents, principals,
      food service directors, nurses, and health educators in Massachusetts. The
      results suggest that while funding can initially enable schools to provide
      quality lunch, but without changes in students' preference for unhealthy food and
      parental and community involvement in fostering students' healthy eating
      behavior, the lunch programs cannot achieve a sustainable success. Lack of
      opportunity for communication among food service staff, health educators, and
      teachers appears to hinder the coordination necessary to promote school lunch as
      well as school-wide nutrition education. Respondents acknowledged that the
      state's academic assessment system is the priority issue in their schools, but
      expressed that the interests and initiatives of superintendents and principals in
      the lunch and nutrition education programs can be enhanced. Overall, the results
      suggest that successful implementation of quality lunch and nutrition education
      programs require not only the collaborative efforts of school administration and
      staff but also the support of parents, community, and the mass media.

PMID- 15471424
TI  - Chronic cholecystitis.

PMID- 15471425
TI  - Intracellular liposomes and cholesterol deposits in chronic cholecystitis and
      biliary sludge.
AB  - Ultrastructural study of a group of selected specimens of chronic cholecystitic
      gallbladders reveals cholecystocyte changes characterized by abraded and altered
      microvilli accompanied by mitochondrial damages in the apical regions as well as
      mucus accumulation with aggregated, angulated lysosomes and heterogeneous
      liposomes. These liposomes contain needle-like crystals, probably rich in
      cholesterol. Many fragments of cholecystocystes and damaged organelles or
      contents can be found in the biliary sludge. These data support previous reports
      suggesting that there is an association between cholecystitis and the presence of
      cholelithiasis, subsequent to the production of altered bile. The present data
      suggest that disintegrating, sloughed cholecystocyte contents also contribute to
      the bile sludge, a complex milieu enriched by lipids, cholesterol deposits,
      altered mucus due in part to changes in expression of apomucins. The instability
      of prolonged storage of such modified bile, caused and/or accompanied by other
      associated metabolic defects, including gallbladder sluggishness, would favor the
      nucleation and the enlargement of gallstones. Based on the aforementioned data, a
      comprehensive sequence for cholecystocyte ultrastructural alterations and
      pathologies is proposed, as a result of chronic cholecystitis.

PMID- 15471426
TI  - Scanning electron microscopy of aortic medial changes in aortic ascending
      dilatation.
AB  - The study of cystic cavities and collagen fibers fragmentation is useful to for a
      better knowledge of pathogenesis and surgical therapy of medial ascending aortic
      degeneration. Thus, the aim of this study was to describe by scanning electron
      microscopy the surfaces and shape of the cysts, measure their area, and identify
      microcystic spaces related to this degenerative disease. Scanning electron
      microscopy analysis was performed in 16 out of 36 patients who underwent surgery
      for ascending aorta dilatation with associated aortic valve disease. The aortic
      medial wall showed a cribrose appearance at low magnification (x50-100) and the
      intima was effuse. At high magnification (x500-2000), small cavities (clefts)
      lined by normal or fragmented elastic fibers and large cavities (pseudocystes)
      with anfractuous borders lined by fragmented elastic fibers and smooth muscle
      cells were observed. Furthermore, in the outer media wall microvessels lined by
      endothelium were also observed. These changes were lacking or less pronounced in
      normal aorta. SEM allows one to better identify the pathological cavities and to
      differentiate them from microvessels. These pathological cavities are more
      numerous and larger in the convexity than in the concavity of the aorta in
      according to our previous morphological and morphometric findings in asymmetrical
      aorta dilatation.

PMID- 15471427
TI  - Papillary serous carcinoma of the ovary: an ultrastructural and
      immunohistochemical study.
AB  - Twenty-four patients with ovarian serous papillary carcinoma were enrolled in the
      present ultrastructural and immunohistochemical study. Immunohistochemistry was
      used to examine the status of proliferation activity with antibodies against Ki67
      and BM28, and the status of EGFR family members with antibodies against EGFR, c
      erbB-2, and c-erbB-4. Ultrastructurally, poorly differentiated tumors often
      revealed solid sheets of tumor cells with variable desmosomes, cell connection
      complexies, and microvilli. No mature cilia, which are often present in benign
      and borderline ovarian epithelial tumors, were seen in these 24 carcinomas.
      However, two poorly differentiated tumors demonstrated oligocilia. In addition,
      numerous secondary lysosomes and bizzare intracytoplasmic pseudocavities were
      more often present in the poorly differentiated tumors. Immunohistochemically,
      strong expressions of BM28 and Ki67 in more than 50% of the tumor cells were
      found in 12/15 (80%) and 11/15 (73%) of the poorly differentiated tumors,
      respectively, compared with 3/9 (33%) and 1/9 (11%) of the moderately
      differentiated tumors, respectively. Higher levels of EGFR and c-erbB-2
      expressions were more often observed in the poorly differentiated tumors,
      compared with that in the moderately differentiated tumors. In conclusion,
      oligocilium, numerous secondary lysosomes, and bizarre intracytoplasmic
      inclusions are more often seen in poorly differentiated ovarian serous
      carcinomas. Poorly differentiated ovarian serous carcinomas express higher levels
      of Ki67, BM28, EGFR, and c-erbB-2 proteins.

PMID- 15471428
TI  - Desmoplastic fibroblastoma: a light and ultrastructural description of two cases.
AB  - The authors report 2 cases of collagenous fibroma in which ultrastructural
      analysis revealed the presence of fibronexus junctions, markers of
      myofibroblastic differentiation, never described in this rare lesion before. The
      tumors occurred in the trapezius muscle and in the right arms of a 41 -year-old
      and a 25-year-old man. They were both intramuscular and showed sharp edges.
      Grossly, the excised masses were whitish and firm. Microscopically, they were
      both composed of stellate or spindle-shaped cells separated by a collagenous
      hypovascular and focally myxoid stroma. Mitotic figures and necrotic areas were
      not identified. Immunohistochemistry showed positivity for vimentin and focal
      positivity for smooth and human muscle actin, and flow cytometry showed the
      tumoral cells to be diploid.

PMID- 15471429
TI  - Cytoplasmic crystalline inclusions in a anaplastic oligoastrocytoma.
AB  - A 41-year-old male presented with an ill-demarcated mass involving the left
      fronto-temporal lobe and the basal ganglia. Light microscopically the tumor was
      diagnosed as an anaplastic oligoastrocytoma. Electron microscopy revealed several
      cytoplasmic crystalline inclusions in tumor cells of oligodendroglial lineage. No
      crystalline inclusions were membrane bound. The morphologic features with unique
      ultrastructural findings are presented.

PMID- 15471430
TI  - Gastrointestinal stromal tumor of the stomach with rhabdoid phenotype:
      immunohistochemical, ultrastructural, and immunoelectron microscopic evaluation.
AB  - A variety of neoplasms with rhabdoid differentiation have been reported in many
      sites. The authors describe a case of gastrointestinal stromal tumor (GIST) of
      the stomach that exhibited prominent rhabdoid features. Immunohistochemically,
      the tumor cells displayed positive staining for vimentin, c-kit, CD34, and alpha
      smooth muscle actin. Ultrastructural examination of the rhabdoid tumor cells
      revealed paranuclear whorls of intermediate filaments, which were immunoreactive
      for vimentin by both light microscopic immunohistochemical and protein A gold
      immunoelectron microscopic techniques. On H&E light microscopic examination
      alone, such a tumor could be mistaken for a variety of epithelial, mesenchymal,
      or other neoplasms that may show rhabdoid features. One report of GIST with a
      rhabdoid histologic phenotype has been described. This is the second known report
      of such a case with immunophenotypic and ultrastructural evaluation, and the
      first case with immunoelectron microscopic examination.

PMID- 15471431
TI  - Granular cell tumor of the intrapancreatic common bile duct: one case report and
      review of the literature.
AB  - A granular cell tumor (GCT) in a 39-year-old white man is reported. It was
      localized in the intrapancreatic part of the common bile duct and caused
      obstruction of the bile downflow. The patient underwent radical surgical
      procedures because a malignant tumor was clinically suspected. Macroscopically,
      the tumor appeared as a duct stricture caused by diffuse infiltration of
      neoplastic cells in the walls. In the cytoplasm smaller and larger PAS-positive
      granules were present and constantly reactive to S-100 and NSE antibodies.
      Ultrastructurally, cytoplasmic granules appeared as membrane-bound vacuoles of
      variable size and shape containing debris, disrupted mitochondria, and myelin
      figures. No basal lamina around cell cytoplasm was observed. GCTs are relatively
      uncommon soft tissue tumors usually presenting in the skin and subcutaneous
      tissues or tongue. The prognosis in any location is quite good, but very rare
      malignant GCTs (1-2%) are documented. Complete excision reduces the risk of
      recurrence. Accurate operative diagnosis seems to be critical when the tumors are
      located in the intrapancreatic common bile duct as in this reported case. Gastro
      pancreatico-duodenectomy is too radical a procedure for such a benign lesion and
      additional assessments and investigations are recommanded before such an
      extensive radical surgery.

PMID- 15471432
TI  - Natural antioxidants may prevent posttraumatic epilepsy: a proposal based on
      experimental animal studies.
AB  - Head injury or hemorrhagic cortical infarction results in extravasation of blood
      and breakdown of red blood cells and hemoglobin. Iron liberated from hemoglobin,
      and hemoglobin itself, are associated with the generation of reactive oxygen
      species (ROS) and reactive nitrogen species (RNS). ROS and RNS have been
      demonstrated to be involved in the mechanism of seizures induced by iron ions in
      the rat brain, an experimental animal model for posttraumatic epilepsy (PTE). ROS
      are responsible for the induction for peroxidation of neural lipids, i.e., an
      injury of neuronal membranes, and also could induce disorders in the excitatory
      and inhibitory neurotransmitters. Antioxidants, such as a phosphate diester of
      vitamin E and C (EPC-K1) and antiepileptic zonisamide, have been known to prevent
      the epileptogenic focus formation, or to attenuate seizure activities in the iron
      injected rat brain. Natural antioxidants, such as alpha-tocopherol, and condensed
      tannins, including (-)-epigallocatechin and (-)-epigallocatechin-3-O-gallate,
      adenosine and its derivative, melatonin, uyaku (Lindera Strychnifolia), fermented
      papaya preparations, Gastrodia elata BI., and Guilingji, have been demonstrated
      to scavenge ROS and/or RNS and to be prophylactic for the occurrence of epileptic
      discharge in the iron-injected rat brain.

PMID- 15471433
TI  - Rapid response of hepatocyte growth factor in pulmonary ischemia in a rat model.
AB  - Hepatocyte growth factor (HGF) is a multifunctional factor implicated in tissue
      regeneration, wound healing, and angiogenesis. HGF was initially thought to be
      liver-specific, but it has become clear that HGF acts on alveolar type II cells
      and bronchial epithelial cells. This study was conducted to determine the role of
      HGF in pulmonary ischemia in a rat model. The first increase of the plasma HGF
      level was noted 30 min after pulmonary ischemia, and reached a peak at 12 h. Real
      time reverse transcription polymerase chain reaction (Real-time RT-PCR) revealed
      that the HGF messenger RNA (mRNA) expression in the injured left lung was
      markedly increased at 1, 6, and 12 h after pulmonary ischemia (P < 0.05). The
      interleukin-1beta (IL-1beta) mRNA expression, one of the inflammatory cytokines
      which induces HGF expression, was markedly increased at 1 h in the injured left
      lung (P = 0.0007). Therefore, we considered that HGF might be mainly induced by
      paracrine mechanisms in pulmonary ischemia. In conclusion, we have shown that the
      expression of HGF was induced in pulmonary ischemia, and may be a useful
      biological marker for the early diagnosis.

PMID- 15471434
TI  - Broccoli consumption and chronic atrophic gastritis among Japanese males: an
      epidemiological investigation.
AB  - Previous in vitro and animal experiments have shown that sulforaphane, which is
      abundant in broccoli, inhibits Helicobacter pylori (H. pylori) infection and
      blocks gastric tumor formation. This suggests that broccoli consumption prevents
      chronic atrophic gastritis (CAG) introduced by H. pylori infection and,
      therefore, gastric cancer. For an epidemiological investigation of the
      relationship between the broccoli consumption and CAG, a cross-sectional study of
      438 male employees, aged 39 to 60 years, of a Japanese steel company was
      conducted. CAG was serologically determined with serum cut-off values set at
      pepsinogen I < or = 70 ng/ml and a ratio of serum pepsinogen I/pepsinogen II < or
      = 3.0. Broccoli consumption (weekly frequency) and diet were monitored by using a
      31-item food frequency questionnaire. The prevalence of CAG among men who ate
      broccoli once or more weekly was twice as high as that among men who consumed a
      negligible amount (P < 0.05). Multiple logistic regression analysis indicated
      that broccoli consumption once or more weekly significantly increased the risk
      for CAG (odds ratio, 3.06; 95% confidence interval, 1.12-8.38; P < 0.05), after
      controlling for age, education, cigarette smoking, and alcohol consumption. The
      present study failed to show an expected association between frequent broccoli
      consumption and a low prevalence of CAG.

PMID- 15471435
TI  - Analysis of HCV genotypes from blood donors shows three new HCV type 6 subgroups
      exist in Myanmar.
AB  - The prevalence of hepatitis C virus (HCV) genotypes in Myanmar in comparison with
      the rest of Southeast Asia is not well known. Serum samples were obtained from
      201 HCV antibody-positive volunteer blood donors in and around the Myanmar city
      of Yangon. Of these, the antibody titers of 101 samples were checked by serial
      dilution using HCV antibody PA test II and Terasaki microplate as a low-cost
      method. To compare antibody titers by this method and RNA identification, we also
      checked HCV-RNA using the Amplicor 2.0 test. Most high-titer groups were positive
      for HCV-RNA. Of the 201 samples, 110 were successfully polymerase chain reaction
      (PCR) amplified. Among them, 35 (31.8%) were of genotype 1, 52 (47.3%) were of
      genotype 3, and 23 (20.9%) were of type 6 variants, and phylogenetic analysis of
      these type 6 variants revealed that 3 new type 6 subgroups exist in Myanmar. We
      named the subgroups M6-1, M6-2, and M6-3. M6-1 and M6-2 were relatively close to
      types 8 and 9, respectively. M6-3, though only found in one sample, was a brand
      new subgroup. These subtypes were not seen in Vietnam, where type 6 group
      variants are widely spread. These findings may be useful for analyzing how and
      when these subgroups were formed.

PMID- 15471436
TI  - Exposure of mouse to high gravitation forces induces long-term potentiation in
      the hippocampus.
AB  - The central nervous system is highly plastic and has been shown to undergo both
      transient and chronic adaptive changes in response to environmental influences.
      The purpose of this study was to investigate the effect of hypergravic field on
      long-term potentiation (LTP) in the mouse hippocampus. Exposure of mice to 4G
      fields for 48 h had no effect on input-output coupling during extracellular
      stimulation of Schaffer collaterals and paired pulse facilitation, suggesting
      that the hypergravic exposure had no detrimental effect on basal
      neurotransmission in the hippocampus. However, the exposure to 4G fields for 48 h
      significantly induced LTP compared with the control mouse hippocampus. In
      contrast, no significant changes of late-phase LTP (L-LTP) were found in the
      hippocampi of mice exposed to the hypergravic field. Exposure of mice to 4G
      fields for 48 h enhanced AMPA receptor phosphorylation but not cyclic AMP
      responsive element binding protein (CREB) phosphorylation. These results suggest
      that exposure to hyperdynamic fields influences the synaptic plasticity in the
      hippocampus.

PMID- 15471437
TI  - High-energy transurethral microwave thermotherapy in patients with benign
      prostatic hyperplasia: comparative study between 30-and 60-minute single
      treatments.
AB  - We retrospectively evaluated the subjective and objective treatment results of
      transurethral microwave thermotherapy (TUMT) for benign prostatic hyperplasia
      (BPH) and explored the difference in effectiveness between 30- and 60-min single
      treatments. From June 1997 through March 2003, 58 men with BPH underwent TUMT
      using the Targis device. Twenty-seven and 31 patients each received a single
      treatment of 60 or 30 min, respectively. Evaluations after treatment included a
      clinical determination of the International Prostate Symptom Score, urodynamic
      assessments by peak flow rate, and magnetic resonance imaging (MRI). In the 60
      min treatment, the symptom score improved significantly, from 17.9 to 9.5 after 2
      months. Similarly, there was a significant improvement in peak flow rate, from
      6.7 to 11.2 ml/sec after 2 months. In the 30-min treatment, the symptom score
      also improved significantly, from 18.4 to 13.4 after 2 weeks. Similarly, there
      was a significant improvement in the peak flow rate, from 6.4 to 11.7 ml/sec
      after 1 month. MRI imaging showed necrosis of the prostate gland 2 weeks after
      either treatment. These results demonstrated that both the 60-min and the 30-min
      treatments were effective for patients with BPH. Moreover, the 30-min treatment
      led to quicker improvement than the 60-min treatment. Thus, a 30-min TUMT
      protocol is considered recommendable for this treatment.

PMID- 15471438
TI  - Evaluation of contour of unruptured cerebral aneurysm using three-dimensional CT
      cisternogram.
AB  - Angiography is gold standard technique as preoperative examination for unruptured
      aneurysmal surgery. Neurosurgeons have observed the unexpected irregular shape
      and size of the aneurysmal dome and neck in many cases of unruptured cerebral
      aneurysms during aneurysmal microsurgery, and known the discrepancy between the
      findings of angiography and operative view. We could not find out the report
      described the preoperative evaluation of outer-wall (contour) of aneurysm. In the
      present study, we attempted to evaluate the outer-wall of an unruptured cerebral
      aneurysm using three-dimensional CT cisternogram (3D-CTC) to provide useful
      preoperative information. The study was performed on three cases of unruptured
      cerebral aneurysm that were identified incidentally by MR angiography. We
      performed three-dimensional CT aniography (3D-CTA) and 3D-CTC for each patient.
      In the present study, we visualized the contours of vessels and aneurysms using a
      3D-CTC in three cases of unruptured cerebral aneurysm. We found the discrepancy
      between the 3D-CTC contour image and the intra-luminal image 3D-CTA image. This
      method may be useful for the decision of the surgical approach and have the
      potential to evaluate the anatomical structure of aneurysmal dome and neck
      preoperatively.

PMID- 15471439
TI  - Biliary reconstruction with right hepatic lobectomy due to delayed management of
      laparoscopic bile duct injuries: a case report.
AB  - We report a case requiring biliary reconstruction with right hepatic lobectomy
      due to biliary strictures caused by continuous cholangitis after laparoscopic
      bile duct injury. The patient, a 55-year-old woman, underwent laparoscopic
      cholecystectomy for cholelithiasis at another hospital. Although a bile leakage
      from the intraabdominal drain was observed several days after the operation, the
      patient was not given adequate treatment to stop the leakage. Two months after
      the initial laparoscopic cholecystectomy, she was referred to our hospital.
      Endoscopic retrograde cholangiopancreatography (ERCP) showed complete obstruction
      of the common hepatic duct, which was caused by clipping during laparoscopic
      cholecystectomy. Cholangiography from percutaneous transhepatic biliary drainage
      (PTBD) catheters revealed that sections of the secondary branches of the right
      intrahepatic bile duct had become constricted due to persistent cholangitis.
      Fortunately, the left hepatic duct was judged to be normal by imaging. Therefore,
      we elected to perform a right hepatic lobectomy and left hepaticojejunostomy,
      because we felt that performing a hepaticojejunostomy without hepatic resection
      would put the patient at risk of continuing to suffer from cholangitis. The
      patient was discharged on the 55 th postoperative day, and, 5 years after
      reconstructive surgery, is healthy and has remained free from biliary strictures
      in the remnant liver. Appropriate decision-making is essential in the treatment
      of biliary injury after laparoscopic cholecystectomy. Surgeons should not
      hesitate to perform biliary reconstruction with hepatic resection to reduce the
      risk of cholangitis or biliary strictures of the remnant liver. More importantly,
      preoperative clear imaging of the biliary tree and suitable management of any
      biliary injury which might occur are necessary to avoid having to perform
      reconstructive surgery.

PMID- 15471440
TI  - Ozonolysis of tetramethylethylene: characterization of cyclic and open-chain
      oligoperoxidic products.
AB  - The ozonolysis of tetramethylethylene (TME) in solution to high conversion in
      nonparticipating solvents at -60 degrees C yields predominantly oligoperoxides.
      For the first time, these products have been characterized using electrospray
      ionization mass spectrometry (ESI-MS) under soft ionization conditions. The
      predominant structure formed in reactions carried out in pentane (up to 2.0 M
      TME) is shown to be the cyclic hexamer of acetone carbonyl oxide (oligocarbonyl
      oxide with degree of polymerization, n = 6), but cyclic structures with n up to
      19 are observed. A small proportion of the oligoperoxides formed are open-chain
      compounds with end groups that suggest that chain termination of oligocarbonyl
      oxides can occur through reaction with either water or hydrogen peroxide.
      Ozonolysis in dried butyl acetate similarly produces mainly cyclic
      oligoperoxides. However, ozonolyses carried out in undried butyl acetate yield
      mainly open-chain oligoperoxides, confirming that propagating carbonyl oxide
      chains are readily terminated by water. Relative amounts of the open-chain
      oligomers so-formed suggest that undried butyl acetate contains ca. 0.1% w/w
      water. The ozonolysis of TME in the participating solvent, methanol, at -60
      degrees C yields 2-methoxyprop-2-yl hydroperoxide via reaction of acetone
      carbonyl oxide with methanol; no oligoperoxidic products are formed in this case.

PMID- 15471442
TI  - Experimental and theoretical investigation of the coarctate cyclization of (2
      Ethynylphenyl)phenyldiazenes.
AB  - A new route to substituted 2-phenyl-2H-indazoles through the cyclization of (2
      ethynylphenyl)phenyldiazenes is presented. A coarctate reaction pathway forms the
      isoindazole carbene under neutral conditions, at moderate temperatures, and
      without the requirement of a carbene stabilizer. A wide variety of previously
      unknown diazene precursors was synthesized and cyclized. Trapping of the carbene
      with a silyl alcohol followed by deprotection affords the 3-hydroxymethyl-2
      phenyl-2H-indazoles in good overall yield. The free carbene could also be trapped
      as a [2 + 1] cycloadduct with 2,3-dimethyl-2-butene.

PMID- 15471441
TI  - Evidence for glycosidic bond rotation in a nucleobase peroxyl radical and its
      effect on tandem lesion formation.
AB  - Nucleobase peroxyl radicals are the major reactive intermediates formed in DNA
      when the biopolymer is exposed to gamma-radiolysis under aerobic conditions. The
      major reaction pathways for the peroxyl radical (1) derived from 5,6-dihydro-2'
      deoxyuridin-6-yl involve pi-bond addition to or hydrogen atom abstraction from
      the adjacent nucleotides to produce tandem lesions. The ability to independently
      generate 1 at a defined site in DNA enabled us to probe its reactivity by varying
      the local DNA structure. The effect of DNA structure variation reveals that 1
      reacts from its syn- and anti-conformations in competition with trapping by
      thiol. These experiments also reveal that tandem lesions will be produced as a
      mixture of diastereomers, which could impact their biological effects.

PMID- 15471443
TI  - Electronic and structural effects on the nonlinear optical behavior in push-pull
      TTF/tricarbonyl chromiun arene complexes.
AB  - A novel D-pi-A system in which tetrathiafulvalene (TTF) and pi-extended TTFs as
      strong electron donors are covalently connected to a tricarbonyl (eta(6)
      arene)chromium complex as the acceptor moiety through a systematically increased
      conjugated bridge of vinylene units (12a-c, 16a-c) have been synthesized by
      Wittig-Horner olefination reaction. The electronic spectra as well as the
      electrochemical data reveal a different behavior of TTF derivatives (12a-c) and
      of exTTF derivatives (16a-c). Cyclic voltammetry shows the influence of the
      tricarbonylchromium arene on the oxidation potentials in compounds 12a-c, and no
      remarkable effect is observed for exTTFs (16a-c). The nonlinear optical
      properties of 12a-c and 16a-c have been calculated by using the ab initio CPHF/6
      31G//B3P86/6-31G model, and the time-dependent density functional theory (TD-DFT)
      method has been used for the calculation of the electronic transitions. The
      calculations reveal that an intraligand charge-transfer transition (ILCT) and the
      metal to ligand charge-transfer transition (MLCT) are responsible for the
      nonlinear response. In addition, the large angles formed by the ground-state
      dipole moment and the vectorial hyperpolarizability are responsible for the
      mubeta values determined experimentally by the EFISH technique.

PMID- 15471444
TI  - Design, synthesis, and evaluation of acyclic C-nucleoside and N-methylated
      derivatives of the ribitylaminopyrimidine substrate of lumazine synthase as
      potential enzyme inhibitors and mechanistic probes.
AB  - Lumazine synthase and riboflavin synthase catalyze the last two steps in the
      biosynthesis of riboflavin, a vitamin that is involved in many critical
      biochemical reactions that are essential for the maintenance of life. To obtain
      inhibitors and structural probes that could be useful in studying the structures
      of bound reaction intermediates, the ribitylamino N-H moiety of the lumazine
      synthase substrate was replaced by CH(2) and N-CH(3) groups. The CH(2)
      replacement unexpectedly and completely abolished the affinity for lumazine
      synthase, thus revealing a critical, yet unexplained, role of the ribitylamino N
      H moiety in conferring affinity for the enzyme. In contrast, the N-CH(3)
      replacement resulted in an inhibitor of both lumazine synthase and riboflavin
      synthase. Replacement of the ribitylamino N-H moiety with epimeric C-F moieties
      led to inhibition of lumazine synthase and riboflavin synthase when combined with
      the replacement of the 5-amino group with a nitro substituent.

PMID- 15471445
TI  - Diastereoselective [2+2]-cycloaddition reactions of unsymmetrical cyclic ketenes
      with imines: synthesis of modified prolines and theoretical study of the reaction
      mechanism.
AB  - The synthesis of enantiomerically pure modified proline derivatives was achieved
      by using spiro beta-lactams as starting material that were prepared in turn by
      the [2+2]-cycloaddition of unsymmetrical cyclic ketenes with optically active
      imines. A theoretical study of the [2+2]-cycloaddition reaction, using density
      functional methods, gave insights on the origin of the observed stereoselectivity
      of the Staudinger reaction. The spiro beta-lactams were transformed in the N-Boc
      derivatives and subjected to nucleophilic ring opening, affording the
      corresponding enantiomerically pure modified proline derivatives, isolated as
      orthogonally protected compounds.

PMID- 15471446
TI  - A DFT study of the Boulton-Katritzky rearrangement of (5R)-4
      nitrosobenz[c]isoxazole and its anion: pseudopericyclic reactions with aromatic
      transition states.
AB  - The nature of the Boulton-Katritzky rearrangement of (5R)-4
      nitrosobenz[c]isoxazole and its anion was studied employing three methodologies:
      calculation of magnetic properties (magnetic susceptibility, magnetic
      susceptibility anisotropy, and the nucleus-independent chemical shifts), the
      natural bonding orbital analysis, and the ACID (anisotropy of the current-induced
      density) method. The deep analysis of the results indicates a pseudopericyclic
      character for these reactions despite the aromaticity of the transition states.

PMID- 15471447
TI  - Gas-phase acidity studies of multiple sites of adenine and adenine derivatives.
AB  - The acidities of multiple sites in the purine nucleobase adenine (1) and adenine
      alkyl derivatives 9-ethyladenine (2), 3-methyladenine (3), 1-methyladenine (4),
      and N,N-dimethyladenine (5) have been investigated for the first time, using
      computational and experimental methods to provide an understanding of adenine
      reactivity. We have previously measured two acidic sites on adenine, with the N9
      site being 19 kcal mol(-)(1) more acidic than the N10 site (333 +/- 2 versus 352
      +/- 4 kcal mol(-)(1), respectively). In this work, we have established that 9
      ethyladenine has two sites more acidic than water: the N10 (352 +/- 4 kcal mol(
      )(1)) and the C8 (374 +/- 2 kcal mol(-)(1)). We have likewise measured two
      acidities for 3-methyladenine, the N10 (347 +/- 4 kcal mol(-)(1)) and the C2 (370
      +/- 3 kcal mol(-)(1)). For 1-methyladenine and N,N-dimethyladenine, we measure
      the N9H acidity to be 331 +/- 2 and 333 +/- 2 kcal mol(-)(1), respectively. We
      believe that the bracketing of only one site for the latter species is a kinetic
      effect, which we discuss further in the paper. Computationally, we have found the
      interesting result that some of the vinylic C-H sites in these purine bases are
      predicted to be much more acidic than water (DeltaH(acid) = 390.7 kcal mol(-)(1))
      in the gas phase, on the order of 373 kcal mol(-)(1). The acidic vinylic C-H
      sites are always adjacent to an N-R group, and this pattern is maintained
      regardless of whether the site is on the five- or six-membered ring of the
      purine. Vinylic C-H sites elsewhere on the purine have calculated acidities of
      about 400 kcal mol(-)(1). The differing acidities are interpreted through
      electrostatic potential calculations. We also relate our results to the
      intriguing biochemical decarboxylation of orotate ribose monophosphate, which
      involves a vinylic anion adjacent to an N-R group; this decarboxylation is the
      last step in the de novo biosynthesis of pyrimidine nucleotides, and the enzyme
      that catalyzes the reaction, orotate ribose monophosphate decarboxylase, has been
      the subject of intense study recently, as its mechanism remains elusive.

PMID- 15471449
TI  - Synthesis of 4-deoxy-L-(and D-)hexoses from chiral noncarbohydrate building
      blocks.
AB  - 4-Deoxy-l-hexoses were synthesized starting from our previously reported reagent
      1 and (R)-benzyl glycidyl ether, which led in few steps to a substituted
      dihydropyran 6. The stereocontrolled hydroxylation of the latter afforded the
      corresponding 4-deoxy-l-hexoses 7a, 9, and 11. The same procedure, starting from
      (S)-benzyl glycidyl ether, enabled the preparation of their d-series enantiomers.

PMID- 15471448
TI  - Rational approach to selective and direct 2-O-alkylation of 5,6-O-isopropylidine
      L-ascorbic acid.
AB  - l-Ascorbic acid is a versatile radical scavenger widely distributed in aerobic
      organisms that plays a central role in the protection of cellular components
      against oxidative damage by free radicals and oxidants. It also functions as a
      physiological reductant for key enzymatic transformations in catecholamine
      neurotransmitters, amidated peptide hormones, and collagen biosynthetic pathways.
      Simple derivatives of l-ascorbic acid have been shown to possess antioxidant,
      antitumor, and immunostimulant activities. The antioxidant and redox properties
      of l-ascorbic acid are closely associated with the electron-rich 2,3-enediol
      moiety of the molecule, and therefore, selective functionalization of the 2- and
      3-OH groups is essential for the detailed structure-activity studies. Reactions
      of 5- and 6-OH-protected ascorbic acid with electrophilic reagents exclusively
      produce the corresponding 3-O-alkylated products under mild basic conditions due
      to the high nucleophilicity of the C-3-OH. Based on the density functional theory
      (B3LYP) electron density calculations, we have devised a novel and general method
      for the direct alkylation of the 2-OH group of ascorbic acid with complete regio-
      and chemoselectivity. We have also carried out a complete spectroscopic analysis
      of two complementary series of 2-O-acetyl-3-O-alkyl- and 2-O-alkyl-3-O
      acetylascorbic acid derivatives to define their spectroscopic characteristics and
      to resolve common inconsistencies in the literature.

PMID- 15471450
TI  - Molecular geometry as a source of chemical information. 3. How H-bonding affects
      aromaticity of the ring in the case of phenol and p-nitrophenol complexes: a
      B3LYP/6-311+G study.
AB  - Molecular geometries of phenol and p-nitrophenol (ArOH) interacting with fluoride
      were optimized at the B3LYP/6-311+G level of theory taking as constraints the
      planarity of the systems and the linearity of the O...H...F moiety. For p
      nitrophenol complexes, the substituent effect stabilization energy (SESE) was
      computed, and for all systems aromaticity indices, HOMA, and out-of-plane
      components of NICS(1) and NICS(1)(zz)() were calculated. SESE values depend
      strongly on the O...F distance, the same as both aromaticity indices. Variation
      in HOMA values for the studied ArOH...F(-) complexes is within the range of 0.55
      to approximately 1.0 and for NICS(1)(zz)() between -12 and -26 ppm. It was also
      found that a decrease in aromaticity is well correlated with the variations of C
      O bond length.

PMID- 15471451
TI  - Correlation of the rates of solvolysis of benzoyl fluoride and a consideration of
      leaving-group effects.
AB  - The specific rates of solvolysis of benzoyl fluoride have been determined at 25.0
      degrees C in 37 pure and binary solvents. Together with seven values from the
      literature, these give a satisfactory correlation over the full range of solvents
      when the extended Grunwald-Winstein equation is applied. The sensitivities to
      changes in solvent nucleophilicity and solvent ionizing power are very similar to
      those for octyl fluoroformate, suggesting that the addition step of an addition
      elimination mechanism is rate determining. In the solvent-composition region
      where benzoyl chloride also shows bimolecular solvolysis, the appreciable
      k(Cl)/k(F) values are proposed as being primarily due to a more efficient ground
      state stabilization for the fluoride.

PMID- 15471452
TI  - Convenient synthesis of nucleoside borane diphosphate analogues: deoxy- and
      ribonucleoside 5'-P(alpha)-boranodiphosphates.
AB  - The nucleoside boranophosphates, having one of the nonbridging phosphate oxygens
      substituted with a borane (BH(3)) group, have shown potential therapeutical
      applications as aptamers, antisense agents, and antiviral prodrugs. An
      oxathiaphospholane approach, which does not require exocyclic amine protection of
      the nucleobase, has been successfully developed to efficiently synthesize 5'
      P(alpha)-boranodiphosphates of 2'-deoxythymidine, adenosine, guanosine, and
      uridine. The approach involves a key intermediate, the borane complex of
      nucleoside 5'-O-1,3,2-oxathiaphospholane 16, that undergoes a ring-opening
      reaction catalyzed by 1,4-diazabicyclo[5.4.0]-undec-7-ene to form the protected
      nucleoside 5'-P(alpha)-boranodiphosphate 18. Treatment of 18 with ammonium
      hydroxide yielded diastereoisomeric mixtures of nucleoside 5'-P(alpha)
      boranodiphosphates 5. This oxathiaphospholane approach ensures the availability
      of nucleoside 5'-P(alpha)-boranodiphosphate analogues needed for antiviral drug
      research.

PMID- 15471453
TI  - Synthesis of 4,5-diaryl-1H-pyrazole-3-ol derivatives as potential COX-2
      inhibitors.
AB  - 4,5-Diaryl-1H-pyrazole-3-ol was utilized as a versatile template to synthesize
      several classes of compounds such as pyrazolo-oxazines 7, pyrazolo-benzooxazines
      9, pyrazolo-oxazoles 10, and its analogues 11a-c as potential COX-2 inhibitors.
      Compounds 11b,c were successfully synthesized with use of pyridinium p
      toluenesulfonate mediated cyclization of the ketal intermediate. Diaryl-pyrazolo
      benzooxazepine analogues were synthesized by using Cu-mediated cyclization of the
      O-alkylated arylbromide intermediate. Arylsulfonamides were synthesized
      efficiently on a large scale with 4-[4-(4-fluorophenyl)-5-hydroxy-2H-pyrazol-3
      yl]benzenesulfonamide 31 template readily synthesized from commercially available
      4-sulfamoyl benzoic acid 29. The structure of a representative compound from each
      class was confirmed by X-ray crystallography. Selected compounds tested for
      inhibitory activity against COX-1 and COX-2 enzymes showed good selectivity for
      COX-2 versus COX-1 enzyme.

PMID- 15471454
TI  - Comparative study of the reactivities of substituted 3-(benzoyl)benzyl carbanions
      in water and in DMSO.
AB  - Benzyl-substituted carbanions produced by photodecarboxylation of ketoprofen
      derivatives have been examined in basic aqueous and DMSO solutions. Product
      studies, combined with kinetic measurements from laser flash photolysis, have
      allowed the determination of absolute rate constants for protonation and intra
      S(N)2 reactions leading to five- and six-membered ring cyclizations; the former
      are significantly faster. Many of the well-known trends in carbanion reactivity
      are placed on an absolute rate basis; thus, intra-S(N)2 are favored in polar
      nonprotic solvents, and the effect is larger for the more hindered carbanion
      centers. Protonation by water is slightly dependent on the nature of the
      carbanion center and is approximately 400 times faster in nonhydroxylic solvents,
      compared with bulk water. As expected, the reactivity for halide leaving groups
      follows the usual order of decreasing bond strengths, i.e., I(-) > Br(-) > Cl(-).

PMID- 15471455
TI  - Ruthenium porphyrin catalyzed tandem sulfonium/ammonium ylide formation and [2,3]
      sigmatropic rearrangement. A concise synthesis of (+/-)-platynecine.
AB  - meso-Tetrakis(p-tolyl)porphyrinatoruthenium(II) carbonyl, [Ru(II)(TTP)(CO)], can
      effect intermolecular sulfonium and ammonium ylide formation by catalytic
      decomposition of diazo compounds such as ethyl diazoacetate (EDA) in the presence
      of allyl sulfides and amines. Exclusive formation of [2,3]-sigmatropic
      rearrangement products (70-80% yields) was observed without [1,2]-rearrangement
      products being detected. The Ru-catalyzed reaction of EDA with disubstituted
      allyl sulfides such as crotyl sulfide produced an equimolar mixture of anti- and
      syn-2-(ethylthio)-3-methyl-4-pentenoic acid ethyl ester. The analogous "EDA + N,N
      dimethylcrotylamine" reaction afforded a mixture of anti- and syn-2-(N,N
      dimethylamino)-3-methyl-4-pentenoic acid ethyl esters with a diastereoselectivity
      of 3:1. The observed catalytic activity of [Ru(II)(TTP)(CO)] for the ylide [2,3]
      sigmatropic rearrangement is comparable to the reported examples involving
      [Rh(2)(CH(3)CO(2))(4)] and [Cu(acac)(2)] as catalyst. Similarly, cyclic sulfonium
      and ammonium ylides can be produced by intramolecular reaction of a diazo group
      tethered to allyl sulfides and amines under the [Ru(II)(TTP)(CO)]-catalyzed
      reaction conditions. The subsequent [2,3]-sigmatropic rearrangement of the cyclic
      ylides furnished 2-allyl-substituted sulfur and nitrogen heterocycles in good
      yields (>90%). By employing [Ru(II)(TTP)(CO)] as catalyst, the cyclic ammonium
      ylide [2,3]-sigmatropic rearrangement reaction was successfully applied for the
      total synthesis of (+/-)-platynecine starting from cis-2-butenediol.

PMID- 15471456
TI  - Room temperature preparation of trifluoroethenylzinc reagent by metalation of the
      readily available halocarbon HFC-134a and an efficient, economically viable
      synthesis of 1,2,2-trifluorostyrenes.
AB  - Trifluoroethenylzinc reagent [CF(2)=CFZnX] was generated from the readily
      available halocarbon HFC-134a by an in situ metalation-transmetalation procedure
      at temperatures near to room temperature (15-20 degrees C). By systematic
      standardization of the metalation experiments by manipulation of solvent,
      cosolvent, temperature, zinc salt, and the base, the trifluoroethenylzinc reagent
      was produced in 73% yield at 20 degrees C in THF medium. The palladium-catalyzed
      cross-coupling reaction of the trifluoroethenylzinc reagent with various aryl
      iodides was carried out under mild reaction conditions to produce 1,2,2
      trifluorostyrenes in 59-86% isolated yields. The stability of the intermediate
      trifluoroethenyllithium reagent was compared at different temperatures and
      solvent systems. Experimental evidence for the mono-anion from HFC-134a
      (CF(3)CHF(-)) was obtained by the trapping of the mono-anion with zinc halide in
      THF/TMEDA medium. The structure and complexation of both the mono- and bis
      trifluoroethenylzinc reagents with TMEDA and other ligands are discussed.

PMID- 15471457
TI  - Chiral phosphinooxazolidine ligands for palladium- and platinum-catalyzed
      asymmetric Diels-Alder reactions.
AB  - Cationic palladium (Pd)- and platinum (Pt)-phosphinooxazolidine catalysts 13a-c,
      15a-d, 17a-c, and 19a-c were prepared from phosphinooxazolidine ligands 1-3,
      MCl(2) (M = Pd and Pt), and counterions, and the activities of the catalysts in
      the asymmetric Diels-Alder (DA) reactions of cyclic or acyclic dienes with imide
      dienophiles were investigated. These catalysts demonstrated high levels of
      catalytic activity. The cationic Pd-POZ complex 13c provided particularly
      excellent enantioselectivity (98% ee) in the DA reactions of cyclopentadiene with
      acryloyl-, crotonyl-, and fumaroyl-1,3-oxazolidin-2-ones (20a-c).

PMID- 15471458
TI  - Antioxidant activity of hydroxystilbene derivatives in homogeneous solution.
AB  - The antioxidant activity of the cis and trans isomers of several analogues of
      resveratrol and pterostilbene has been investigated, especially with regard to
      the effect of the stereochemistry about the olefinic double bond. The antioxidant
      power of these compounds was estimated by measuring the rate constants for their
      reactions with peroxyl radicals and, with two of them, the bond dissociation
      enthalpy (BDE) of the phenolic O-H bond which is cleaved in the inhibition
      reaction. The present data show that in homogeneous solution the various
      hydroxystilbenes investigated behave as mild antioxidants with the notable
      exceptions of the trans isomer of 4 and 6, whose activities are only slightly
      lower than that of alpha-tocopherol (vitamin E). The rate constants of the
      inhibition reaction show that the antioxidant activity of the cis-hydroxystilbene
      is in all the examined cases worse, by a factor ranging between 2 and 6, than
      that of the corresponding trans isomers. This lower reactivity depends on
      enthalpy factors as it can be inferred by the experimental values of the O-H bond
      dissociation enthalpy in the two geometric isomers of 3',5'-di-tert-butyl-4'
      hydroxy-3,5-dimethoxystilbene showing that the strength of the O-H bond in the
      cis isomer is larger by 1.8 kcal/mol. DFT calculations provide a rationalization
      of this result, indicating that, although the cis geometry implies a
      destabilization with respect to the trans species of both phenoxyl radical and
      parent hydroxystilbene, the destabilization of the radical is larger because the
      folding of the structure strongly reduces the delocalization of the unpaired
      electron on the styryl group. A comparison of these results with previously
      reported data on the proapoptotic activity of these stilbenoids suggests that
      these two properties are not correlated.

PMID- 15471459
TI  - Synthesis and use of stereospecifically deuterated analogues of palmitic Acid to
      investigate the stereochemical course of the delta11 desaturase of the
      processionary moth.
AB  - Thaumetopoea pityocampa pheromone glands contain desaturases that, after several
      sequential reactions from palmitic acid, catalyze the formation of a unique enyne
      fatty acid, which is the immediate sex pheromone precursor. In this article, we
      describe the synthesis of different stereospecifically deuterium-labeled and
      isotopically tagged palmitic acid probes needed to decipher the stereochemical
      course of the T. pityocampa Delta(11) desaturase. The synthesis of probes has
      been carried out by a chemoenzymatic route, in which the key step is the kinetic
      lipase-catalyzed resolution of racemic mixtures of secondary propargyl alcohols.
      The presence of the acetylenic bond simplifies the absolute configuration
      determination of the resolved alcohols. Moreover, it allows the introduction of
      the isotopic tag by deuteration. By use of the probes thus prepared, experimental
      evidence is presented that the Delta(11) desaturase of T. pityocampa transforms
      palmitic acid into (Z)-11-hexadecenoic acid by removal of the pro-(R)-hydrogen
      atoms from both C11 and C12.

PMID- 15471460
TI  - A straightforward and versatile synthetic approach to 1-azabicyclic alkaloids.
AB  - A very straightforward route to 1-azabicyclo alkaloid scaffolds with several ring
      sizes is reported. The final bicyclic structures were built through a synthetic
      scheme that involved (i) the construction of dienic 4-piperidone systems by an
      imino-Diels-Alder reaction between aminotrienes and N-omega-vinylimines, in the
      presence of Yb(OTf)(3), and (ii) the ring-closing metathesis reaction of these
      cyclic dienes, under the influence of the first-generation Grubbs' Ru-complex
      catalyst. During this investigations, various polysubstituted azabicyclic ring
      skeletons, including several examples of the quinolizidine alkaloids, are
      reported, and their relative stereochemistry is adequately discussed.

PMID- 15471461
TI  - Photolytic, thermal, addition, and cycloaddition reactions of 2-diazo-5,6- and 
      3,8-disubstituted acenaphthenones.
AB  - Preparation and varied thermal and photolytic reactions of 2-diazo-5,6
      (disubstituted)acenaphthenones (11a-d) and 2-diazo-3,8-dimethoxyacenaphthenone
      (12) are reported. Alcohols react thermally and photolytically with 11a-c with
      losses of N(2) to yield 2-alkoxynaphthenones (24a,band 47a,b) and acenaphthenones
      (25 and 48a,b). Aniline and diphenylamine are converted by 11a-c at 180 degrees C
      to acenaph[1,2-b]indoles (29a,b and 53a,b). Thermolyses of 11a-c at approximately
      450 degrees C (0.15 mmHg) yield reduction products 25 and 48a,b, respectively.
      Wolff rearrangements to 1,8-naphthyleneketenes (15a-d) and/or their derivatives
      are not observed in the above experiments. Oxygen converts 11a-c thermally to
      acenaphthenequinones (19a-c) and/or 1,8-naphthalic anhydrides. Insertion,
      addition, substitution, and/or isomerization reactions occur upon irradiation of
      2-diazoacenaphthenones in cyclohexane, benzene, and tetrahydrofuran. Photolysis
      of 11d in benzene in the presence of O(2) yields the insertion-oxidation product
      2-hydroxy-5,6-dinitro-2-phenylacenaphthenone (60). Photolyses of 11a-c in
      nitriles result in N(2) evolution and dipolar cycloaddition to give acenaph[1,2
      d]oxazoles (41 and 61a,b). Acetylenes undergo thermal and photolytic
      cycloaddition/1,5-sigmatropic rearrangement reactions with 11a-d with N(2)
      retention to give pyrazolo[5,1-a]quinolin-7-ones (69f-j). 2-Diazoacenaphthenones
      1a and 11a react thermally and photolytically with electronegatively-substituted
      olefins with N(2) expulsion to yield (E)- and (Z)-2-oxospiro[acenaphthylene
      1(2H),1'cyclopropanes] 73a-c and 74a-c, respectively. The mechanisms of the
      reactions of 1a, 11a-d, and 12 reported are discussed.

PMID- 15471462
TI  - Pyramidalized olefins: a DFT study of bicyclo[2.1.1]-, -[3.2.1]-, and 
      [3.2.2]alkenes and their fused derivatives. Two rare examples of pi-facially
      symmetric pyramidal olefins.
AB  - Density functional theory (B3LYP/6-31G) was used to study a large series of
      bridged polycyclic alkenes based on the bicyclo[2.1.1], -[3.2.1], and -[3.2.2]
      nuclei. In those compounds with pi-facial dissymmetry, butterfly bending of the
      strained olefinic bonds was generally predicted. Surprisingly, large
      pyramidalizations are calculated for the highly strained but pi-facially
      symmetric tetracyclo[5.1.1.1.(3,5)0(2,6)]dec-2-ene (28, psi = 19.8 degrees ) and
      tetracyclo[5.2.2.1.(3,5)0(2,6)]dodec-2,8,10-triene (33, psi = 14.4 degrees ). The
      preference for propano-directed bending in the bicyclo[3.2.1]octenes is about as
      strong as that for endo bending in norbornenes.

PMID- 15471463
TI  - On the lack of conjugation stabilization in polyynes (polyacetylenes).
AB  - By analogy to conjugated polyenes, conjugative stabilization of polyynes with the
      -CC-CC- group might be expected to be substantial. On the contrary, consistent
      with our recent report of a surprising lack of conjugative stabilization in
      butadiyne, we find by G3(MP2) calculations and by comparisons with available
      experimental data from these and other laboratories that the ground-state
      stabilization of conjugated polyynes is in fact quite small, amounting to <1 kcal
      mol(-)(1). By similar calculations, the 2,4-pentadiyn-1-yl radical shows no
      enhanced stabilization relative to 2-propyn-1-yl radical, despite the potential
      stabilization of the odd electron by two conjugated triple bonds and unlike the
      behavior of 2,4-pentadien-1-yl radical. The thermochemistry of straight-chain
      alkynes and polyynes is very self-consistent. Enthalpies of hydrogenation,
      leading to enthalpies of formation, are predictable with a high degree of
      accuracy (absolute mean deviation = +/-0.39 kcal mol(-)(1) vs theoretical values
      and +/-0.52 vs experimental) from three molecular structure enthalpies and one
      conjugation stabilization parameter.

PMID- 15471464
TI  - The preference for anti over Gauche migration in the Baeyer-Villiger reaction.
AB  - Explanations for stereoselectivity in the Baeyer-Villiger reaction have relied on
      the assumption that the antiperiplanar (app) group migrates. However, the
      magnitude of the preference for app-migration over gauche migration is unknown.
      To investigate this, the energy differences between the two were estimated from
      ab initio calculations. App-migration was found to be the preferred pathway since
      no transition structure could be located for gauche migration. Barriers for
      gauche migration were estimated by performing constrained optimizations. App
      migration was found to be strongly favored with a barrier that is at least 3.8
      kcal/mol and as much as 58.0 kcal/mol lower in energy than the gauche migration
      barrier.

PMID- 15471465
TI  - Silylstannylation of allenes and silylstannylation-cyclization of allenynes.
      Synthesis of highly functionalized allylstannanes and carbocyclic and
      heterocyclic compounds.
AB  - Catalyzed by Pd(0), trialkylsilyltrialkylstannane (R(3)Si-SnR'(3)) reagents
      undergo highly selective additions to 1,2-dien-7-ynes and 1,2-dien-8-ynes to give
      2-vinylalkylidenecyclopentanes with silicon and tin substituents on the double
      bonds. Similar additions of distannanes and borostannanes show that the reactions
      with silylstannanes are superior in terms of ease of handling of the bifunctional
      reagents and the isolation of the products after the reaction. The chemo- and
      regioselectivities are controlled by the enhanced reactivity of the allene unit,
      while the (Z)-geometry of the exocyclic stannylvinylidene is a consequence of the
      syn-carbometalation and subsequent reductive elimination from Pd with retention
      of configuration at the vinyl carbon. Synthesis of highly functionalized
      pyrrolidines and indolizidines and the reluctance of certain kinds of allenynes
      and silicon-tin reagents to undergo the cyclization illustrate the scope and
      limitations of the reaction. Based on the isolation of intermediates, a mechanism
      for the formation of the cyclic compounds is proposed. Model transition states to
      explain the stereoselectivity in cyclization of substituted allenynes are
      provided. Further elaboration using the vinyltin and vinylsilane moieties should
      lead to highly functionalized carbocyclic and heterocyclic compounds. Under
      similar conditions, addition of silylstannanes to highly functionalized allenes
      gives E-allylstannanes with high stereoselectivity. Functional groups such as THP
      and silyl-ethers, lactones, beta- and gamma-lactams, alpha,beta-unsaturated
      esters, olefins, and substituted acetylenes are tolerated under the reaction
      conditions.

PMID- 15471466
TI  - Intramolecular inverse-electron-demand Diels-Alder reactions of imidazoles with
      1,2,4-triazines: a new route to 1,2,3,4-tetrahydro-1,5-naphthyridines and related
      heterocycles.
AB  - The intramolecular inverse-electron-demand Diels-Alder reaction between
      imidazoles and 1,2,4-triazines linked by a trimethylene tether from the imidazole
      N1 position to the triazine C3 proceed in excellent yields to produce 1,2,3,4
      tetrahydro-1,5-naphthyridines. The reaction proceeds by a cycloaddition with
      subsequent loss of nitrogen, followed by a presumed stepwise loss of a nitrile.
      The analogous intramolecular cycloadditions employing a tetramethylene tether
      also proceeded to give 2,3,4,5-tetrahydro-1H-pyrido[3,2-b]azepines in acceptable
      yields. The reaction to produce the tetrahydro-1,5-naphthyridines can also be
      promoted with microwave irradiation.

PMID- 15471467
TI  - Synthesis and photophysical properties of ferrocene-oligothiophene-fullerene
      triads.
AB  - To promote photoinduced charge separation previously observed for the
      oligothiophene-fullerene dyads (nT-C60), we have designed an additional
      attachment with a strongly electron-donating ferrocene at the unsubstituted
      terminal site of the oligothiophene and synthesized two types of the ferrocene
      oligothiophene-fullerene triads, Fc-nT-C60 directly linking the ferrocene to the
      oligothiophene and Fc-tm-nT-C60 inserting a trimethylene spacer between the
      ferrocene and the oligothiophene. For the central oligothiophene of the triads, a
      homologous series of quaterthiophene (4T), octithiophene (8T), and
      duodecithiophene (12T) are systematically examined. The cyclic voltammograms and
      electronic absorption spectra of Fc-nT-C60 indicate conjugation between the
      ferrocene and oligothiophene components. The emission spectra of Fc-nT-C60
      measured in toluene demonstrate that the fluorescence of the oligothiophene is
      markedly quenched, as compared to that observed for the dyads nT-C60. This
      quenching is explained in terms of the involvement of intramolecular electron
      transfer in the photophysical decay process. The additionally conjugated
      ferrocene evidently contributes to the stabilization of charge separation states,
      thus promoting intramolecular electron transfer. This is corroborated by the
      observation that the emission spectra of the nonconjugated triads Fc-tm-nT-C60
      are essentially similar to the corresponding dyads nT-C60.

PMID- 15471468
TI  - Generation of synthetic equivalents of benzdiynes from benzobisoxadisiloles.
AB  - Linear and angular benzobisoxadisiloles 14 and 16 can serve as the precursors for
      stepwise generations of the syntetic equivalents of 1,4- and 1,3-benzdiynes.
      Benzynes generated were trapped as [4+2] cycloaddition products. Two identical or
      different rings can be fused to the benzdiyne equivalents. Highly substituted
      arenes were obtained by removing the oxygen bridges from the furan adducts. The
      synthesis of naphthoxadisilole 28, which can serve as the precursor of 2,3
      naphthyne, is also described.

PMID- 15471469
TI  - Asymmetric hetero-Diels-Alder reactions of N-sulfinyl dienophiles using chiral
      bis(oxazoline)-copper(II) and -zinc(II) triflates.
AB  - Asymmetric hetero-Diels-Alder (HDA) reactions of N-sulfinyl dienophiles using
      bis(oxazoline)-copper(II) and -zinc(II) triflates are described. The
      cycloadditions with cyclic and acyclic 1,3-dienes have been studied. In most
      cases, good enantioselectivities (70-98% ee) and yields (60-85%) were obtained
      with stoichiometric amounts of the Lewis acids. Cyclic dienes gave the endo
      adducts as major products, while acyclic dienes provided cis adducts. The HDA
      adducts have been transformed into N-protected alpha-amino acid methyl esters,
      amino alcohols, and homoallylic amines. A stereochemical model, which accounts
      for the enantiofacial selectivity of the HDA reaction by a tetrahedral metal
      center, has been proposed. Mechanistic studies revealed positive nonlinear
      effects, assumed to arise from the formation of less-reactive heterochiral
      complexes. Investigation of the temperature dependence of the enantioselectivity
      indicated that at least two selective reaction steps exist in the zinc-catalyzed
      reaction. Reactions run with 10 mol % chiral Lewis acid gave poor yields and
      selectivities. However, in combination with TMSOTf (100 mol %), high yields (68
      86%) and enantioselectivities (97-98% ee) were obtained.

PMID- 15471470
TI  - Temperature-controlled regioselectivity in the reductive cleavage of p
      methoxybenzylidene acetals.
AB  - The regioselective ring opening of pyranosidic 4,6-p-methoxybenzylidene acetals
      with BH(3)/Bu(2)BOTf in THF can be tuned by adjusting the reaction temperature
      and reagent concentrations. Reductive cleavage at 0 degrees C resulted in the
      exclusive formation of 4-O-p-methoxybenzyl (PMB) ethers, whereas reaction at -78
      degrees C produced 6-O-PMB ethers in high yields. The latter condition was
      observed to be compatible with a variety of acid-sensitive functional groups,
      including allyl and enol ethers. The presence of water does not interfere with
      reductive ring opening and may contribute toward in situ generation of H(+) as a
      catalyst for 6-O-PMB ether formation. Reductive cleavage under rigorously aprotic
      conditions is greatly decelerated, and yields only the 4-O-PMB ether. The
      temperature-dependent reductive cleavage of the 4,6-acetal can be described in
      terms of kinetic versus thermodynamic control: Lewis-acid coordination of the
      more accessible O-6 is favored at higher temperatures, whereas protonation of the
      more basic but sterically encumbered O-4 predominates at low temperatures.

PMID- 15471471
TI  - Deuterium kinetic isotope effects and mechanism of the thermal isomerization of
      bicyclo[4.2.0]oct-7-ene to 1,3-cyclooctadiene.
AB  - The thermal conversion of cis-bicyclo[4.2.0]oct-7-ene to cis,cis-1,3
      cyclooctadiene might involve a direct disrotatory ring opening, or it might
      possibly take place by way of cis,trans-1,3-cyclooctadiene. This cis,trans-diene
      might possibly form the more stable cis,cis isomer through a [1,5] hydrogen shift
      or a trans-to-cis isomerization about the trans double bond. Deuterium kinetic
      isotope effect determinations for the isomerizations of 2,2,5,5-d(4)
      bicyclo[4.2.0]oct-7-ene and 7,8-d(2)-bicyclo[4.2.0]oct-7-ene rule out these two
      alternatives because the observed effects are much smaller than would be
      anticipated for these mechanisms: k(H)/k(D)(d(4)) at 250 degrees C is 1.17 (1.04
      per D), and k(H)/k(D)(d(2)) at 238 degrees C is 1.20 (1.10 per D). The direct
      disrotatory ring opening route remains the preferred mechanism.

PMID- 15471472
TI  - Diastereoselective syntheses of new analogues of the farnesyltransferase
      inhibitor RPR 130401.
AB  - The access to several benzo[f]perhydroisoindolic analogues of farnesyltransferase
      inhibitors from a single dienic precursor is reported. An initial [4 + 2]
      cycloaddition between diphenylisobenzofuran6 and pyrrolines 11, 14, and 15 led to
      either the syn or the anti isomers, depending on the mode of activation of the
      cycloaddition. The syn diastereomers were isolated in 90% de under 12 kbar at
      room temperature, while their anti counterparts were obtained with the same
      selectivity by warming the reaction mixture to 110 degrees C in toluene at
      atmospheric pressure. Both syn and anti adducts were separately N-deprotected,
      and the resulting amines reacted with an activated ester derived from the acid
      (20) to afford the final targets (5). Two new analogues (5a and 5b) of the FT
      inhibitor RPR 130401 were thus synthesized in a mere three-step synthetic scheme
      with overall yields from 30 to 60%.

PMID- 15471473
TI  - An antenna-sensitized nitroindoline precursor to enable photorelease of L
      glutamate in high concentrations.
AB  - 1-Acyl-7-nitroindolines are useful reagents for rapid release of carboxylates
      upon flash photolysis in aqueous solution and have been particularly effective
      for rapid (submicrosecond) release of neuroactive amino acids such as l-glutamate
      in biological experiments. In model systems the efficiency of photorelease has
      been shown to be greatly improved by attachment of a benzophenone triplet
      sensitizing antenna. The present work describes synthesis and initial biological
      evaluation of the l-glutamate precursor 3. A significant improvement in the
      overall synthesis uses double Boc protection of the glutamate amino group to
      avoid side reactions during introduction of the nitro group. To accommodate the
      multiple functionalities in 3, linkage of the nitroindoline and benzophenone
      moieties is carried out late in the synthesis. Photolysis of 3 occurs with near
      quantitative stoichiometry and the released l-glutamate efficiently activates
      neuronal glutamate ion channels.

PMID- 15471474
TI  - A flexible enantioselective synthesis of the isofurans.
AB  - Recently, the isolation of a new class of human arachidonic acid tetrahydrofuran
      oxidation products, the isofurans (IsoF's), was reported. These new compounds are
      available from natural sources only in microgram quantities as mixtures. The
      enantioselective preparation of a versatile epoxide intermediate and its
      conversion to the enantiomerically pure isofurans SC-Delta(13)-9-IsoF and 15-epi
      SC-Delta(13)-9-IsoF are described. This synthesis will make these metabolites
      available for physiological evaluation.

PMID- 15471475
TI  - Alpha-trifluoromethylation of secondary and sterically hindered carboxylates with
      use of BrF3.
AB  - Secondary esters and those with sterical hindrance at the beta carbon were
      reacted with base, carbon disulfide, and methyl iodide to produce methyl 2
      carboalkoxydithioalkenoate (2). These compounds were reacted with BrF(3), forming
      the corresponding alpha-trifluoromethyl esters (3) along with 1,1-difluoro-2
      trifluoromethyl-2-alkyl ethers (4). The products of type 4 have been transformed
      to derivatives of type 3, thus raising the overall yields of the target
      respective alpha-trifluoromethyl esters to 65-80%. The reaction is tolerant to
      different functional groups such as halogens, protected alcohols, esters, and
      lactones.

PMID- 15471476
TI  - An orbital phase theory for the torquoselectivity of the ring-opening reactions
      of 3-substituted cyclobutenes: geminal bond participation.
AB  - We apply an orbital phase theory to the torquoselectivity of the electrocyclic
      reactions of 3-substituted (X) cyclobutenes. The torquoselectivity is shown to be
      controlled by the orbital-phase relation of the reacting pi(CC) and sigma(CC)
      bonds with the sigma(CX) bond geminal to the sigma(CC) bond to be cleaved. The
      inward rotation of electron-donating sigma(CX) bonds and outward rotation of
      electron-withdrawing sigma(CX) bonds have been deduced from the orbital-phase
      theory. Enhancement of the inward rotation by the electron-donating capability of
      the sigma(CX) bonds is confirmed by the correlation between the torquoselectivity
      and sigma(CX) orbital energy. The orbital overlaps between the geminal sigma(CX)
      (sigma(CH)) and sigma(CC) bonds are found to be important as well. Unsaturated
      substituents with low-lying unoccupied pi orbitals also promote the inward
      rotation.

PMID- 15471477
TI  - Theoretical calculations of the effects of 2-heavier group 14 element and
      substituents on the singlet-triplet energy gap in cyclopentane-1,3-diyls and
      computational prediction of the reactivity of singlet 2-silacyclopentane-1,3
      diyls.
AB  - UDFT and CASSCF calculations with the 6-31G(d) basis set were performed to
      investigate the heavier group 14 element (M) effect on the ground-state spin
      multiplicity of cyclopentane-1,3-diyls and their reactivity. The calculations
      find that 2-metallacyclopentane-1,3-diyls (M = Si, Ge) that possess a variety of
      substituents (X = H, Me, F, OR, SiH(3)) at M(2) are singlet ground-state
      molecules. The energies of the 1,3-diphenyl-substituted singlet 2
      silacyclopentane-1,3-diyls are calculated to be ca. 5 kcal/mol lower than those
      of the intramolecular ring-closure products, i.e., 1,4-diphenyl-5
      silabicyclo[2.1.0]pentanes, at the B3LYP/6-31G(d) level of theory. The energy
      barrier for the disrotatory ring closure of singlet 2,2-dimethyl-1,3-diphenyl-2
      silacyclopentane-1,3-diyl (lambda(calcd) = 757 nm, f = 1.01 at RCIS/6-31G(d)) to
      the corresponding 5-silabicyclo[2.1.0]pentane is computed to be 11.6 kcal/mol,
      which is 13.1 kcal/mol lower in energy than that for the conrotatory ring-opening
      to a 3-silapenta-1,4-diene. The computational work predicts that singlet 1,3
      diaryl-2-silacyclopentane-1,3-diyls are persistent molecules under conditions
      without trapping agents.

PMID- 15471478
TI  - Photonucleophilic aromatic substitution of 6-fluoroquinolones in basic media:
      triplet quenching by hydroxide anion.
AB  - Photoreaction of 1-ethyl-6-fluoro-7-(1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3
      carboxylic acid (norfloxacin, NFX) and other 6-fluoroquinolones in aqueous
      solution gives rise to the corresponding 6-hydroxy derivatives. Although two
      mechanisms have been proposed for this photonucleophilic aromatic substitution,
      direct evidence for any of them is still missing. Obtaining such evidence
      requires work in basic media, where intramolecular electron transfer from the
      piperazine ring to the quinolone system is the almost exclusive singlet
      deactivation pathway. To overcome this problem, the 4'-N-acetyl derivative of
      norfloxacin (ANFX) has been employed in the present paper due to the lower
      availability of the N lone pair. The photochemical and photophysical properties
      of ANFX have been studied in aqueous solutions at pH between 7.4 and 13. As
      expected, fluorescence of ANFX is not significantly quenched in basic media.
      Furthermore, the excited triplet state (lambda(max) = 620 nm) reacts with
      hydroxide anions with a rate constant of (0.3 +/- 0.1) x 10(6) M(-)(1) s(-)(1).
      This supports a direct attack by hydroxide anions to the excited triplet state
      with subsequent release of fluoride as the operating mechanism. The fact that the
      reaction is inhibited by the presence of naproxen (a water-soluble naphthalene
      derivative) as triplet quencher clearly confirms the mechanistic assignment.

PMID- 15471479
TI  - A synthetic approach toward the proposed tetracyclic aziridinomitosene derived
      from FK317.
AB  - A synthesis of the FK317 derivative 25 is described using internal Michael
      addition. Tin-lithium exchange of the deuterated stannylaziridine 18 generated
      the key lithioaziridine intermediate, followed by cyclization and aromatization
      of the pyrrole ring to give 7. Ester reduction from 7 to 23 was effected via
      temporary aldehyde protection as the silylimidazole adduct 22, and conversion to
      the carbamate 25 was carried out using FmocNCO and FMOC cleavage. Structure 25 is
      the N-trityl-protected derivative of the proposed intermediate from bioactivation
      of FK317 that is responsible for DNA cross-linking. Attempted nitrogen
      deprotection of 25 using MsOH/i-Pr(3)SiH resulted in replacement of the C(10)
      carbamate by hydride. Deprotection of the more stable 21 gave the desired
      aziridine 26.

PMID- 15471480
TI  - Manifestation of stereoelectronic effects on the calculated carbon-hydrogen bond
      lengths and one-bond 1J(C-H) NMR coupling constants. Relative acceptor ability of
      the carbonyl (C=O), thiocarbonyl (C=S), and methylidene (C=CH2) groups toward C-H
      donor bonds.
AB  - Theoretical examination [B3LYP/6-31G(d,p), PP/IGLO-III//B3LYP/6-31G(d,p), and NBO
      methods] of six-membered cyclohexane 1 and carbonyl-, thiocarbonyl-, or
      methylidene-containing derivatives 2-27 afforded precise structural (in
      particular, C-H bond distances) and spectroscopic (specifically, one-bond
      (1)J(C)(-)(H) NMR coupling constants) data that show the consequences of
      stereoelectronic hyperconjugative effects in these systems. Major observations
      include the following. (1) sigma(C)(-)(H)(ax)() -->(C)(=)(Y) and pi(C)(=)(Y) -->
      sigma(C)(-)(H)(ax)() (Y = O, S, or CH(2)) hyperconjugation leads to a shortening
      (strengthening) of the equatorial C-H bonds adjacent to the pi group. This effect
      is reflected in smaller (1)J(C)(-)(H)(ax)() coupling constants relative to
      (1)J(C)(-)(H)(eq)(). (2) Comparison of the structural and spectroscopic
      consequences of sigma(C)(-)(H)(ax)() --> pi(C)(=)(Y) hyperconjugation in
      cyclohexanone 2, thiocyclohexanone 3, and methylenecyclohexane 4 suggests a
      relative order of acceptor orbital ability C=S > C=O > C=CH(2), which is in line
      with available pK(a) data. (3) Analysis of the structural and spectroscopic data
      gathered for heterocyclic derivatives 5-12 reveals some additivity of sigma(C)(
      )(H)(ax)() --> pi(C)(=)(Y), pi(C)(=)(Y) --> sigma(C)(-)(H)(ax)(), n(X) -->
      sigma(C)(-)(H)(ax)(), n(beta)(O) --> sigma(C)(-)(H)(eq)(), and sigma(S)(-)(C) -->
      sigma(C)(-)(H)(eq)() stereoelectronic effects that is, nevertheless, attenuated
      by saturation effects. (4) Modulation of the C=Y acceptor character of the
      exocyclic pigroup by conjugation with alpha-heteroatoms O, N, and S in lactones,
      lactams, and methylidenic analogues 13-24 results in decreased sigma(C)(
      )(H)(ax)() --> pi(C)(=)(Y) and pi(C)(=)(Y) --> sigma(C)(-)(H)(ax)()
      hyperconjugation. (5) Additivity of sigma(C)(-)(H)(ax)() --> pi(C)(=)(Y) and
      pi(C)(=)(Y) --> sigma(C)(-)(H)(ax)() hyperconjugative effects is also apparent in
      1,3-dicarbonyl derivative 25 (C=Y equal to C=O), 1,3-dithiocarbonyl derivative 26
      (C=Y equal to C=S), and 1,3-dimethylidenic analogue 27 (C=Y equal to C=CH(2)).

PMID- 15471481
TI  - Stereoselective synthesis of the antiprotozoal lactone passifloricin A and seven
      isomers thereof.
AB  - The conjugated delta-lactone passifloricin A, a natural product with
      antiprotozoal activity, and seven isomers thereof have been synthesized in
      enantiopure form. It has been shown in this way that the proposed structure for
      the natural compound was erroneous. The correct structure is now evidenced. Key
      steps of the syntheses were asymmetric Brown-type aldehyde allylations and ring
      closing metatheses.

PMID- 15471482
TI  - Stereoselective synthesis of polyhydroxylated indolizidines based on pyridinium
      salt photochemistry and ring rearrangement metathesis.
AB  - Ruthenium-catalyzed ring rearrangement metathesis (RRM) reactions of
      stereochemically diverse, differentially protected 4-N-allylacetamidocyclopenten
      3,5-diols, prepared by using pyridinium salt photochemistry, have been explored
      as part of a program to develop novel routes for the synthesis of
      polyhydroxylated indolizidines. The RRM reactions, which produce selectively
      protected 1-acetyl-2-allyl-3-hydroxy-1,2,3,6-tetrahydropyridines, were found to
      take in high yields and with high levels of regioselectivity. The significance of
      RRM reactions of 4-N-allylacetamidocyclopenten-3,5-diols in the context of
      polyhydroxylated indolizidine synthesis is demonstrated by an application to the
      concise preparation of the potent glycosidase inhibitor, (-)-swainsonine.

PMID- 15471483
TI  - Synthesis of Spirovetivane Sesquiterpenes from Santonin. Synthesis of (+)-Anhydro
      beta-rotunol and all diastereomers of 6,11-spirovetivadiene.
AB  - The synthesis of the spirovetivane sesquiterpenes (+)-anhydro-beta-rotunol and
      all the diastereomers of 6,11-spirovetivadiene in enantiomerically pure form has
      been achieved starting from santonin. The key step is the silicon-guided acid
      promoted rearrangement of a 1-trimethylsilyl-4,5-epoxyeudesmane prepared from
      santonin in several steps involving lactone reductive opening, conjugate addition
      of TMSLi-CuCN, deoxygenation of a carbonyl group, and epoxidation. Rearrangement
      of the epoxide gave a spiro[4,5]decanediol which was used as a synthetic
      intermediate. From this compound, (+)-anhydro-beta-rotunol was prepared after
      elimination of the primary hydroxyl group in the side chain, followed by allylic
      oxidation at C8 and elimination of the tertiary hydroxyl group in the cyclohexane
      ring. On the other hand, elimination of the hydroxyl group in the side chain and
      reduction of the hydroxyl in the cyclohexane ring gave (-)-premnaspirodiene and (
      )-hinesene. The synthesis of the rest of the diastereomers for these compounds
      required formal inversion of the C5 spiro carbon. The synthesis of these
      compounds showed that the structure of (-)-agarospirene isolated from Scapania
      sp. was erroneously assigned, and it has been corrected to be identical to that
      of (-)-hinesene.

PMID- 15471484
TI  - Reactivity of chiral alpha-amidoalkylphenyl sulfones with stabilized carbanions.
      stereoselective synthesis of optically active 1-aminopyrrolizidine.
AB  - Metal enolates and functionalized allylzinc reagents react with optically active
      alpha-amidoalkylphenyl sulfones to give N-carbamoylamino derivatives with
      variable levels of anti diastereoselectivity. Zinc enolates provide comparable
      results with respect to lithium enolates in terms of diastereoselectivity but
      afford beta-amino ester derivatives in lower yield. The synthetic utility of the
      obtained chiral N-carbamoylamino esters is demonstrated by the first
      enantioselective synthesis of (-)-1-aminopyrrolizidine a central intermediate for
      the preparation of various biologically active substances.

PMID- 15471485
TI  - Mitomycin synthetic studies: stereocontrolled and convergent synthesis of a fully
      elaborated aziridinomitosane.
AB  - Full details of a stereocontrolled and convergent synthetic route to 9a
      desmethoxymitomycin A (1) are reported. The target molecule possesses the parent
      tetrahydropyrrolo[1,2-a]indole ring system characteristic of the mitomycin family
      of antitumor agents. The synthesis was based on the diastereocontrolled addition
      of a fully elaborated cinnamylstannane to a pyrrolidine-based N-acyliminium ion
      as the key convergent step, which resulted in the installation of the C9 and C9a
      stereogenic centers.

PMID- 15471486
TI  - Computational studies of nucleophilic substitution at carbonyl carbon: the S(N)2
      mechanism versus the tetrahedral intermediate in organic synthesis.
AB  - A theoretical study specifically addresses the question of whether nucleophilic
      addition to the carbonyl groups of acid chlorides, esters, and anhydrides
      involves an addition-elimination pathway or proceeds by a concerted S(N)2-like
      mechanism in the absence of the generally assumed tetrahedral intermediate.
      Density functional calculations [B3LYP/6-31+G(d,p)] establish that chloride ion
      exchange reactions with both formyl and acetyl chloride proceed by a pi attack on
      the C=O bond. No discernible tetrahedral intermediate typical of an addition
      elimination pathway was found in either case. While a tetrahedral intermediate
      does exist for the addition of fluoride ion to (Cl)(2)C=O, halide exchange of
      LiCl with both ClFC=O and (Cl)(2)C=O also proceeds by a concerted S(N)2-like
      pathway. The formation of a tetrahedral intermediate from the addition of
      methanol to acetyl chloride is slightly exothermic (4.4 kcal/mol). The ion-dipole
      complex of methanol weakly bonded to the carbonyl carbon of protonated acetyl
      chloride is stabilized by 13.8 kcal/mol but does not collapse to a tetrahedral
      intermediate. When four CH(3)OH molecules are H-bonded to protonated acetyl
      chloride, a tetrahedral intermediate is not completely formed and this solvated
      complex more closely resembles the precursor to an S(N)1-type ionization of Cl(
      ). With six H-bonding methanol molecules, a methanol adds to the carbonyl carbon
      and a proton relay occurs with formation of a tetrahedral-like structure that
      immediately loses chloride ion in an S(N)1-like solvolysis. These results
      corroborate earlier suggestions (Bentley et al. J. Org. Chem. 1996, 61, 7927)
      that the methanolysis of acetyl chloride does not proceed through the generally
      assumed addition-elimination pathway with a discrete tetrahedral intermediate but
      is consistent with ionization of Cl(-). The reaction of methoxide ion with methyl
      acetate proceeds via a multiple-well energy surface and involves the intermediacy
      of an asymmetrical species with differing C-OMe bond lengths. Models of synthetic
      applications of acyl transfer reactions involving anhydrides that form N
      acyloxazolidinones also proceed by a concerted S(N)2-type pathway even with the
      carboxylate leaving group. Concerted transition states were observed for the
      reactions of each enantiomer of a 1,3-diphenylcycloprop-2-ene carboxylic
      anhydride by S-3-lithio-4-phenyloxazolidinone. Despite close structural
      similarities between the diastereomeric transition states, the relative energies
      correlated closely with the experimental results.

PMID- 15471487
TI  - Intermolecular coupling of alkenes to heterocycles via C-H bond activation.
AB  - The intermolecular coupling of unactivated alkenes to a range of heterocycles
      using a Rh(I) catalyst was investigated. A variety of functional groups were
      incorporated into the alkene, including esters, nitriles, acetals, and
      phthalimide. Furthermore, the heterocycle tolerated substitution with both
      electron-rich and electron-deficient groups. The intermolecular coupling became
      possible after it was discovered that weak acids dramatically increase the rate
      of both the inter- and intramolecular reactions. An extensive optimization of
      additives was performed, and HCl.PCy(3) (Cy = cyclohexyl) and HCl.P-t-Bu(2)Et
      were in general found to be the best additives for the reaction.

PMID- 15471489
TI  - Reestimation of the Taft's substituent constant of the pentafluorophenyl group.
AB  - The Taft's substituent constant of the pentafluorophenyl group (sigma(C(6)F(5)))
      was reestimated to be 1.50 by correlation between IR spectral data (v(C)(=)(O))
      and sigma constants for a series of esters (involving the pentafluorobenzyl
      group) of 3-phenylpropanoic acid and butanoic acid. The possibility of the
      disturbance of the correlation by the intramolecular pi-pi interaction between
      C(6)F(5) and C(6)H(5) groups in pentafluorobenzyl 3-phenylpropanoate was excluded
      by ab initio and DFT calculations of the stable conformations and their carbonyl
      frequencies. The reestimated sigma(C(6)F(5)) value was used for calculation of
      the pK(a) value of pentafluorobenzyl alcohol [14.5 (or 14.3)].

PMID- 15471488
TI  - Nucleophilic substitution by grignard reagents on sulfur mustards.
AB  - With proper activation of the leaving group, sulfur mustards react with Grignard
      reagents with neighboring group participation of the sulfur atom. 2,6-Dichloro-9
      thiabicyclo[3.3.1]nonane is especially useful in this regard, providing clean
      reactivity with organomagnesium nucleophiles on a topologically constrained
      scaffold.

PMID- 15471490
TI  - Stereoselective synthesis of photoreactive peptidomimetic gamma-secretase
      inhibitors.
AB  - The first asymmetric synthesis of novel, potent photoreactive gamma-secretase
      inhibitors 2 and 3 has been accomplished. Two stereoselective methods for the
      preparation of lactone 9 are described. Protected benzophenone intermediate 19 is
      prepared via an aldol-elimination reaction followed by a PtO(2)-catalyzed
      asymmetric hydrogenation. Two routes leading from 19 to compounds 2 and 3 are
      evaluated. The application of 3 as an activity-based probe has been demonstrated
      by localizing gamma-secretase activity in the plasma membrane of intact cells.

PMID- 15471491
TI  - Enantiospecific access to various C(9),C(10)-disubstituted camphors: scope and
      limitations.
AB  - The valuable chiral sources C(9),C(10)-disubstituted camphors can be
      enantiospecifically obtained from the corresponding C(9)-substituted camphors by
      a general and straightforward synthetic method. This method involves the
      electrophilic treatment of a key 2-methylenenorbornan-1-ol intermediate, followed
      by a controlled tandem carbon-carbon double-bond addition-Wagner-Meerwein
      rearrangement of the norbornane framework. Discussion of the results presented
      suggests possible extensions and limitations of the methodology used. The
      feasibility of this method has been exemplified by the highly efficient
      enantiospecific preparation of several interesting C(9)-halogen-, C(10)-halogen,
      O-, S-, or Se-substituted camphors.

PMID- 15471492
TI  - Fluoride-promoted oxidation of Fischer alkoxy carbene complexes: stoichiometric
      and catalytic conditions.
AB  - The utility of fluoride anion as promoter of the oxidation of Fischer carbene
      complexes is presented. Two different and complementary methods that allow the
      fast and convenient preparation of carbene-derived esters in good yields have
      been developed using stoichiometric or catalytic quantities of fluoride ion.

PMID- 15471493
TI  - Stereoselective synthesis of P-chiral phosphorus compounds from N-tert
      butoxycarbonyl amino acids.
AB  - Reaction of the N-t-Boc amino acids alanine and valine with PhPCl(2) gives the P
      chiral trans-1,3,2-oxazaphospholidinones exclusively. Variable-temperature NMR
      and examination of the glycine derivative shows that the isomers observed are due
      to t-Boc rotation.

PMID- 15471494
TI  - Synthesis of carboalkoxychloro- and bromodiazirines.
AB  - The first known 3H-diazirines bearing a carbonyl group and a halogen atom on C-3
      have been prepared by a novel synthetic method. Carboalkoxychloro- and
      bromodiazirines 1a-d are formed in up to 45% yields by reductive dechlorination
      of carboalkoxy-N,N,N'-trichloroformamidines 9a,b using chloride or bromide ion.
      This method constitutes the first example of the use of N,N,N'-trichloroamidines
      as starting materials in organic synthesis.

PMID- 15471495
TI  - Cross-linking dendrimers with allyl ether end-groups using the ring-closing
      metathesis reaction.
AB  - A third generation Frechet-type dendrimer containing 24 allyl ether end-groups
      was synthesized, cross-linked using the ring-closing metathesis (RCM) reaction,
      and the core was removed hydrolytically without significant fragmentation. The
      results are analogous to those previously reported for homoallyl ether dendrimers
      (Wendland, M. S.; Zimmerman, S. C. J. Am. Chem. Soc. 1999, 121, 1389-1390)
      suggesting that the less readily available homoallyl ether dendrimers can be
      replaced by their allyl ethers analogues in a range of applications.

PMID- 15471496
TI  - Synthesis of thioglycoside-based UDP-sugar analogues.
AB  - Arbuzov reaction of O-acetyl-protected glycosylthiomethyl chlorides with triethyl
      phosphite and then phosphonate ethyl ester cleavage with trimethylsilyl bromide
      afforded glycosylthiomethyl phosphonates 13, 18, 22, and 26. These intermediates
      could be readily transformed into the O-deprotected phosphonates 7-10 and into
      title compounds 1-4. Similarly, sulfonomethyl phosphonate moieties containing UDP
      sugar analogues 5 and 6 were obtained.

PMID- 15471497
TI  - Ortho-selective nucleophilic aromatic substitution reactions of polyhaloanilines
      with potassium/sodium o-ethyl xanthate: a convenient access to halogenated 2(3H)
      benzothiazolethiones.
AB  - Polyhaloanilines bearing an ortho halogen atom undergo smooth nucleophilic
      aromatic substitution reactions with anionic sulfur nucleophiles at relatively
      mild temperatures (95-120 degrees C). These reactions are very efficient and
      highly ortho-selective. With potassium/sodium O-ethyl xanthate as a nucleophile,
      subsequent cyclization follows to afford halogenated 2(3H)-benzothiazolethiones
      (2-mercaptobenzothiazoles) in high yields.

PMID- 15471498
TI  - Synthesis of (-)-noviose from 2,3-O-isopropylidene-D-erythronolactol.
AB  - Noviose is a key synthon for the construction of novobiocin, a clinically useful
      antitumor agent that has been shown to inhibit both type II topoisomerases and
      Hsp90. The synthesis of d-noviose from 2,3-O-isopropylidene-d-erythronolactol is
      described.

PMID- 15471499
TI  - Simple, facile, and one-pot conversion of the Baylis-Hillman adducts into
      functionalized 1,2,3,4-tetrahydroacridines and cyclopenta[b]quinolines.
AB  - A simple, facile, and one-pot synthesis of functionalized 1,2,3,4
      tetrahydroacridines and cyclopenta[b]quinolines from the Baylis-Hillman alcohols,
      i.e., 2-[hydroxy(2-nitroaryl)methyl]cycloalk-2-enones, is described.

PMID- 15471500
TI  - Stereospecific uncatalyzed alpha-O-glycosylation and alpha-C-glycosidation by
      means of a new D-Gulal-derived alpha vinyl oxirane.
AB  - The reaction of alpha vinyl oxirane 5, prepared through a new route to the d
      gulal system, with O-nucleophiles (alcohols and di-O-isopropylidene-alpha-d
      monosaccharides) and C-nucleophiles (lithium alkyls) affords, in a completely
      stereoselective way, the corresponding 2-unsaturated alpha O- and C-glycosides
      having the same configuration as the starting epoxide.

PMID- 15471501
TI  - An efficient, stereoselective approach to syn-1,2-diols protected as cyclic
      carbonates.
AB  - Enantioenriched 4-hydroxyalk-2-ynyl carbonates (or benzoates) have been prepared
      by stereoselective zinc-mediated addition of alkyl 2-propynyl carbonates (or
      their benzoate analogues) to aldehydes. Their partial reduction to Z-olefins
      followed by cyclization under mild Pd-catalyzed conditions allowed a
      straightforward access to enantioenriched syn-1,2-diols protected as cyclic
      carbonates.

PMID- 15471502
TI  - Asymmetric transfer hydrogenation of alpha-aminoalkyl alpha'-chloromethyl ketones
      with chiral Rh complexes.
AB  - Asymmetric transfer hydrogenation of N-substituted (3S)-3-amino-1-chloro-4-phenyl
      2-butanones in the presence of CpRhCl[(R,R)-Tsdpen] (S/C = 1000) with a mixture
      of formic acid/triethylamine gave N-substituted (2R,3S)-3-amino-1-chloro-2
      hydroxy-4-phenylbutanes with up to 93% de in a quantitative yield, and reduction
      with the enantiomeric catalyst CpRhCl[(S,S)-Tsdpen] gave (2S,3S)-diastereomeric
      alcohol with up to 96% de.

PMID- 15471503
TI  - First synthesis of a branched beta-C-tetrasaccharide using a triple ring closing
      metathesis cyclization.
AB  - The first synthesis of a branched beta-C-tetrasaccharide has been carried out
      through the use of an esterification-ring closing metathesis (RCM) strategy. The
      precursor triacid 2a was readily prepared via standard chemical methods from a
      known starting material, and dehydrative coupling with an excess of olefin
      alcohol 1a gave triester 3a in excellent yield. Methylenation of the triester 3a
      and subsequent triple RCM reaction was followed by an in situ hydroboration
      oxidation to furnish the branched beta-C-tetrasaccharide 6a in good overall
      yield.

PMID- 15471504
TI  - Conformational studies of peptides containing cis-3-hydroxy-D-proline.
AB  - Conformational analysis of peptides containing cis-3-hydroxy-d-proline (d-cis-3
      Hyp) by NMR studies revealed that the 3-hydroxyl group in this amino acid plays a
      significant role in the overall three-dimensional structures of the peptides.
      When the d-cis-3-Hyp had its 3-hydroxyl group protected as the benzyl (Bn) ether,
      the peptide displayed a beta-hairpin structure in both CDCl(3) and DMSO-d(6).
      Even after the removal of the Bn group, the resulting deprotected compound
      retained the same structure as in the protected version in CDCl(3). However, in
      polar solvent DMSO-d(6), the C-terminal strand of the hydroxyl-deprotected
      peptide flipped to the side of the hydroxyl group, breaking the hairpin to form a
      pseudo beta-turn-like nine-membered ring structure involving an intramolecular
      hydrogen bond between LeuNH --> HypC3-OH.

PMID- 15471505
TI  - Should tamoxifen be used in breast cancer prevention?
AB  - Breast cancer is the most commonly diagnosed cancer in women. The risk of
      developing breast cancer can be lowered by maintaining a healthy bodyweight and
      avoiding long-term use of combined estrogen and progestogen replacement after
      menopause. However, many women are at an increased risk of developing breast
      cancer secondary to age, early menarche, a family history of breast cancer or a
      personal history of benign breast disease. These women may now be offered
      tamoxifen as a chemoprevention therapy. Five years of tamoxifen treatment results
      in a reduction in the relative risk of developing estrogen receptor-positive
      breast cancer of 48%. This benefit outweighs the risk of tamoxifen-related
      adverse events for many healthy women. However, the benefit-risk ratio of
      tamoxifen chemoprevention varies for individual women. The randomized clinical
      trials evaluating standard-dose tamoxifen versus placebo as chemoprevention
      therapy are reviewed and analyzed to determine which particular women are most
      likely to benefit and least likely to experience a tamoxifen-related adverse
      event. Tamoxifen decreases the risk of breast cancer associated with aging,
      having a first-degree relative with disease, and a personal diagnosis of atypical
      ductal hyperplasia or lobular carcinoma in situ. Women who have had a
      hysterectomy and are at low risk of a thromboembolic event have a decreased risk
      of adverse effects associated with tamoxifen therapy. The strengths and
      weaknesses of the Gail model (frequently used to assess an individual's risk of
      developing invasive breast cancer over the next 5 years) are highlighted. A
      method for assessing the benefit-risk ratio for an individual woman is presented.
      Alternative breast cancer chemoprevention strategies are considered, including
      the use of aromatase inhibitors. This article discusses the pros and cons of
      these various preventive therapies and concludes that at this time, tamoxifen
      remains the gold standard for breast cancer prevention.

PMID- 15471506
TI  - Use of selective serotonin reuptake inhibitors in children and adolescents.
AB  - Depression is a serious condition, associated with considerable morbidity and
      mortality; selective serotonin reuptake inhibitors (SSRIs) were commonly used in
      its treatment in child and adolescent psychiatry until recently. In the wake of
      the recent UK Committee on Safety of Medicines (CSM) advice, we conducted a rapid
      review of current available information on SSRIs and suicidality (suicidal
      ideation, self-harm and suicide attempt) in children and adolescents from
      clinical trials and epidemiological studies. There is insufficient safety
      information from the randomised controlled trials to confirm a definite
      association between SSRIs and suicidality. Furthermore, analysis of suicide and
      antidepressant prescribing trends in three countries and a large case-control
      study do not support the hypothesis that there is a link between use of SSRIs and
      death caused by suicide. Regulatory agencies and the media should have strict
      guidelines for the management of information relating to the treatment of this
      condition so that clinicians can make properly informed decisions. We suggest
      clinical guidelines for managing depression in children and adolescents. SSRIs
      should not be considered for use as first-line treatment in mild or moderate
      depression of childhood, where psychological interventions such as cognitive
      behaviour therapy or interpersonal therapy are the mainstay. SSRIs should be
      considered when there is severe depression that does not respond to psychological
      interventions; when the child is suicidal and is admitted as an inpatient, is
      severely depressed or has bipolar depression despite adequate doses of mood
      stabilisation agents; or when the child or family prefers pharmacotherapy to
      psychological interventions and gives informed consent. Local bodies of
      clinicians or peer groups should agree protocols and acceptable guidelines,
      taking into consideration the type of patients being assessed, the availability
      of nonpharmacological intervention, and the benefit-risk ratio of the
      pharmacological intervention. It is important that parents (and patients when
      possible) be given accurate information regarding the current controversy over
      SSRI prescribing. More research into the use of SSRIs in childhood depression is
      urgently required.

PMID- 15471507
TI  - Safety of a new oral contraceptive containing drospirenone.
AB  - New chemical entities must undergo rigorous, and preferably independent, safety
      and efficacy assessments before entry into the market. This is also true for oral
      contraceptives (OCs) given their extensive usage by healthy women and the safety
      concerns highlighted by the so-called 'third generation pill scare' in Europe a
      decade ago. This scare heightened patient and physician awareness of the
      increased risk of thromboembolic complications (mainly venous thromboembolism
      [VTE]) associated with OC use. Yasmin (ethinylestradiol 30 microg/drospirenone 3
      mg [EE/DRSP]) is a novel OC that was demonstrated in clinical phase I-III studies
      to be highly effective in preventing pregnancy and to have a good safety profile.
      Nonetheless, clinical trials are not usually sufficiently powered to detect rare
      adverse events such as VTE to enable comparison with other OCs, which could allay
      fears and concerns about their inherent risks. Therefore, an extensive assessment
      of the VTE risk associated with EE/DRSP has been undertaken by reviewing data
      from the clinical development programme, postmarketing surveillance and
      spontaneous worldwide reporting, as well as information from other sources.
      Spontaneous worldwide reporting has revealed a VTE reporting rate of 5.1/100 000
      women-years with EE/DRSP use. In contrast, 3-year interim results from a large,
      controlled, prospective postmarketing surveillance study suggest a VTE rate of
      61/100 000 women-years for EE/DRSP, which is similar to the rates of 60/100 000
      and 73/100 000 women-years for levonorgestrel-containing OCs and other OCs,
      respectively. When placed in context with potential biases and confounding
      factors that would inflate the perceived risk of VTEs with a novel OC, the VTE
      rate with EE/DRSP does not highlight any safety concerns. Furthermore, the risk
      of VTE with EE/DRSP or other OCs is far less than that associated with pregnancy
      and delivery (up to 800/100 000 women-years) or than other risks of daily living.
      Available data indicate that EE/DRSP is not associated with any increased risk of
      other serious adverse events such as hyperkalaemia, cardiac arrhythmia or birth
      defects. Nonetheless, caution should be exerted in prescribing EE/DRSP to women
      with conditions that predispose to hyperkalaemia.Overall, the safety data with
      EE/DRSP and other OCs indicate that these products have no negative impact on the
      risk of VTE (and other adverse events) in women who receive OCs for
      contraception.

PMID- 15471508
TI  - Treatment costs to prevent or treat upper gastrointestinal adverse events
      associated with NSAIDs.
AB  - The widespread use of nonselective NSAIDs and cyclo-oxygenase (COX)-2 inhibitors
      has a substantial impact on healthcare budgets worldwide. The cost of their
      gastrointestinal (GI) adverse effects is a major component of their direct cost
      and has received much attention in the literature. Published studies have often
      differed in their methodologies and results. It is important for decision makers
      to understand the reasons for these differences in order to make informed
      decisions. We conducted a literature review to summarise data that evaluate the
      direct costs of NSAID-related GI adverse effects worldwide. This resulted in 789
      articles from which 29 studies met the inclusion criteria and were fully
      reviewed. Of these 29, the 9 studies that assessed the cost of COX-2 inhibitors
      were all based on decision economic models, compared with only 7 of the remaining
      20 studies, which assessed the cost of nonselective NSAIDs. In most studies, the
      perspective was that of the healthcare payer and the costs assessed were
      reimbursement costs. Costs of GI events almost doubled between regular users and
      non-users of nonselective NSAIDs and were much higher in high-dose versus low
      dose users. The ratio of the total cost of nonselective NSAIDs to their
      acquisition cost reported in all studies varied from 1.36 to 2.12. Both of these
      numbers were reported in one single study assessing several different NSAIDs in
      France. Thus, the GI adverse events attributable to nonselective NSAIDs are
      substantial, and their costs often exceed the cost of the nonselective NSAID
      itself.The acquisition cost of the COX-2 inhibitors was the main driver of their
      total cost. The GI adverse effects with the COX-2 inhibitors added 10-20% to
      their acquisition cost in North America, while this increase was about 50% in
      some European countries. Decision analysis models showed that the direct costs of
      COX-2 inhibitors were lower than those of nonselective NSAIDs in patients at risk
      of NSAID gastropathy but higher in patients at no to low risk of gastropathy.
      Thus, from an economic perspective, the healthcare system would benefit from
      treating patients at risk of NSAID gastropathy with COX-2 inhibitors, but not
      those at no to low risk.

PMID- 15471509
TI  - Benefit-risk assessment of tolterodine in the treatment of overactive bladder in
      adults.
AB  - Overactive bladder is associated with symptoms of urgency, with or without urge
      incontinence, usually with daytime frequency and nocturia in the absence of local
      pathological factors. Muscarinic receptor antagonists (antimuscarinics) are the
      first-line pharmacotherapy. Tolterodine, a competitive, nonselective
      antimuscarinic specifically developed for the treatment of overactive bladder,
      demonstrated tissue selectivity for the bladder over the parotid gland in an
      animal model. As of March 5, 2003, the immediate-release (IR) formulation had
      been approved in 72 countries and the extended-release (ER) formulation had been
      approved in 28 countries, and tolterodine had been administered to 5 million
      patients. This review evaluates the benefit-risk profile of tolterodine in the
      treatment of adults with overactive bladder, summarising clinical trial and
      postmarketing surveillance data. Tolterodine has been found to significantly
      reduce micturition frequency, urgency perception and the number of episodes of
      urge incontinence and increase the volume voided per micturition. Dry mouth, an
      antimuscarinic class effect, is the most commonly reported adverse effect but is
      mostly mild to moderate in severity. Serious adverse effects are reported
      infrequently. Based on summary and review of postmarketing surveillance and
      clinical trial safety data received by the market authorization holder and
      contained in the Periodic Safety Update Reports for tolterodine, several
      monitored serious events of the gastrointestinal tract (e.g. ileus or
      haemorrhage), nervous system (e.g. syncope, convulsions and memory disorders) and
      cardiovascular system (e.g. ventricular arrhythmia, atrial fibrillation,
      palpitations, bradycardia, transient ischaemic attacks and hypertension) were not
      considered related to tolterodine. QT or corrected QT (QTc) prolongation was not
      observed in any of the five cases of verified ventricular arrhythmia in patients
      administered tolterodine; there is insufficient evidence to indicate that
      tolterodine causes ventricular arrhythmia or extrasystoles or any specific type
      of cardiac rhythm abnormality. The safety profile of tolterodine is similar in
      patients aged > or =65 years and in younger adults. Clinically relevant drug
      interactions are limited to cytochrome P450 3A4 inhibitors, such as ketoconazole,
      and co-administration with such agents warrants a tolterodine dosage decrease. In
      addition, tolterodine IR 2mg twice daily is similar in efficacy to oxybutynin IR
      5mg three times daily, and tolterodine ER 4 mg once daily is similar in efficacy
      to oxybutynin ER 10mg once daily. Dry mouth occurred less frequently with
      tolterodine than oxybutynin, and moderate to severe dry mouth occurred more than
      three times less frequently. Based on the low frequency of adverse events, the
      absence of unexpected adverse events and the very low frequency of serious
      adverse events, we conclude that tolterodine is a well tolerated treatment for
      overactive bladder in adults, in whom it should be considered as first-line
      therapy.

PMID- 15471510
TI  - The impact of unlicensed and off-label drug use on adverse drug reactions in
      paediatric patients.
AB  - BACKGROUND AND OBJECTIVE: Many drugs that are used to treat children are either
      not licensed for use in paediatric patients (unlicensed) or prescribed outside
      the terms of the product licence (off label). The incidence of adverse drug
      reactions (ADRs) associated with the use of such drugs is yet to be established.
      This study investigates, for the first time in a German patient population, the
      impact of unlicensed and off-label drug use on ADRs in paediatric patients.
      PATIENTS AND METHODS: An 8-month prospective pharmacoepidemiological cohort-based
      survey was conducted on a ten-bed paediatric isolation ward at the University
      Hospital Erlangen-Nuremberg, Germany. All patients were intensively monitored for
      ADRs by a pharmacoepidemiological team. ADRs were characterised according to
      international classification methods. All drug prescriptions were evaluated
      retrospectively as to unlicensed or off-label use on the basis of the product
      information. RESULTS: A total of 178 patients were included in the study and 740
      drug prescriptions were given to 156 patients (median three prescriptions per
      patient). In 198 cases (27.7% of all prescriptions) drugs were used in either an
      unlicensed (n = 3) or off-label (n = 195) manner. A total of 46 ADRs were
      observed in 31 patients (17.4%). Patients receiving at least one unlicensed or
      off-label drug prescription during hospitalisation (n = 92) experienced an ADR
      significantly more frequently (n = 26 patients) than patients receiving only
      licensed drugs (n = 64 vs 5 patients). ADRs were associated with 29 (5.6%) of the
      517 licensed drug prescriptions and with 12 (6.1%) of the 198 unlicensed or off
      label drug prescriptions. The majority of ADRs caused by unlicensed and off-label
      drug use were recognised by the attending physician. However, statistical
      analysis revealed no significant difference in the number of licensed and
      unlicensed/off-label drug prescriptions causing ADRs. CONCLUSION: This study
      demonstrated that at a paediatric isolation ward the incidence of ADRs caused by
      unlicensed or off-label drug use was not significantly more than that caused by
      the licensed drug use. However, patients treated with unlicensed or off-label
      drugs were shown to possess a significantly increased risk for developing ADRs.

PMID- 15471511
TI  - Empirical classification of behavioral and psychiatric problems in children and
      adolescents with mental retardation.
AB  - A quantitative method for typing psychopathology of youngsters with mental
      retardation was assessed. Parents of 601 students in special educational
      placements rated them with the ABC. The sample was randomly divided into two
      subgroups. We used Ward's hierarchical method of cluster analysis and derived
      eight clusters in Subsample 1 and satisfactory agreement, kappa =.64, for the
      eight-cluster solution in Subsample 2. Clusters were: Problem Free, Within Normal
      Limits, Conduct Problem, Shy/Inactive, Hyperactive, Social Withdrawal With
      Agitation, Undifferentiated Behavior Disturbance, and Autistic-Like Behavior. We
      also used demographic (age, gender, IQ, physical handicaps) and clinical
      variables (DSM diagnoses and target behaviors) extracted from school records of
      228 participants to appraise validity of the empirically derived clusters. The
      external data provided modest to strong support for all except one cluster
      (Social Withdrawal With Agitation).

PMID- 15471512
TI  - Verbal and visuospatial working memory deficits in children with Down syndrome.
AB  - The hypothesis that deficits of children with Down syndrome on working memory
      tasks are more evident the higher the control required and for verbal than
      visuospatial tasks was tested. Two groups of children, one with Down syndrome,
      who ranged in age from 7 to 18, and a control group were assessed with batteries
      of verbal and visuospatial working memory tests requiring different levels of
      control. On tasks requiring low control, children with Down syndrome showed
      impairment of verbal but not visuospatial working memory tasks. As the
      requirement for control increased, they showed greater impairment on both tasks.
      Children with Down syndrome were comparatively better in visuospatial than verbal
      tasks. Implications of these results for working memory models and the role of
      working memory in intelligence were discussed.

PMID- 15471513
TI  - Semantic and phonological loop effects on verbal working memory in middle-age
      adults with mental retardation.
AB  - Semantic and phonological loop effects on verbal working memory were examined
      among middle-age adults with Down syndrome and those with unspecified mental
      retardation in the context of Baddeley's working memory model. Recall was poorer
      for phonologically similar, semantically similar, and long words compared to
      recall of dissimilar short words. Compared to their peers, participants with Down
      syndrome had poorer recall in all categories except phonologically similar words.
      Most interestingly, semantic similarity lowered recall scores only in
      participants with Down syndrome. This selective effect of semantics reflects an
      influence of long-term memory on working memory and points to the need for
      additional explanations outside phonological loop processes to completely account
      for the relative impairment of verbal working memory among individuals with Down
      syndrome.

PMID- 15471514
TI  - Multiperspective analysis of workforce challenges and their effects on consumer
      and family quality of life.
AB  - The impacts of direct support professional turnover, wages, and vacancy rates as
      reported in interviews with 372 adult service recipients and 20 county managers
      and surveys of 183 families, 520 service coordinators, 228 direct support
      professionals, and 184 residential and 82 vocational managers were examined.
      Direct support professional turnover, wages, and vacancy rates were reported to
      be barriers to high quality supports, serving people waiting for services, and
      providing in-home or respite services. Higher direct support professional
      turnover was associated with lower wages and supports in urban counties.
      Multivariate analyses of covariance revealed a complex pattern of significant
      associations between quality of life outcomes; level of mental retardation,
      medical status, site size (for vocational settings); and direct support
      professional vacancy rates, average wage, and turnover rates.

PMID- 15471515
TI  - Prevalence of eating disorders in adults with mental retardation living in the
      community.
AB  - The prevalence of eating disorders among 311 adults with mental retardation
      living in the West Coast of Norway was investigated. Reports stemming from a
      questionnaire completed by health workers were the data source. Diagnostic
      criteria adapted for persons with mental retardation were used. The main finding
      was that 27% of cases showed indices of an eating disorder. Among the eating
      disorders, binge-eating was the most prevalent. Incidence of anorexia nervosa was
      higher than that of the general population. Findings suggest that eating
      disorders are more prevalent in this population than in the general population.

PMID- 15471516
TI  - Family problem-solving with children who have mental retardation.
AB  - Problem-solving discussions were observed within families of children with mental
      retardation and multiple comparison groups (total N = 162 families). As expected,
      parents were more persistent and directive with their children who had mental
      retardation, but they also avoided negative exchanges with these children. These
      patterns did not spillover to interactions with the siblings, though older
      siblings of young children with mental retardation engaged in frequent negative
      exchanges with the parents. Irrespective of disability status, child behavior
      problems were associated with negative parent-child interactions. Also, high
      levels of family cohesion and independence and low levels of enmeshment and
      disengagement were associated with fewer negative parent-child exchanges, though
      these effects were less pronounced for interactions, specifically with children
      who have mental retardation.

PMID- 15471518
TI  - Quality versus quantity?

PMID- 15471519
TI  - Zinc oxide-eugenol and calcium hydroxide pulpectomies in baboon primary molars:
      histological responses.
AB  - AIM: To compare histological responses to zinc oxide-eugenol (ZOE) and calcium
      hydroxide (CH) pulpectomies in primary molar teeth with inflamed pulps. STUDY
      DESIGN: This was an experimental study in 17 juvenile baboons (Papio ursinus).
      METHODS: Pulpitis was induced with fresh human carious dentine or Streptococcus
      mutans placed into occlusal cavities in 78 primary molars; after 14 days a
      pulpectomy was performed on the same primary molars with the two root fillings
      randomly allocated. The root canal openings were then covered with IRM and the
      cavity filled with amalgam. After 90 days specimens were harvested and examined
      under the light microscope with the examiner blind to the treatment. RESULTS:
      Reaction frequencies in the ZOE-treated versus CH-treated teeth were: no
      recognisable pulp 89% and 82%, internal root resorption 0% and 1%, external root
      resorption 11% and 24%, presence of bacteria 5% and 18%, periapical abscesses 24%
      and 52%. STATISTICS: Fisher's exact probability test showed a statistically
      significant higher prevalence of periapical abscesses in the CH-treated group
      (P=0.03, relative risk 2.2). CONCLUSIONS: ZOE pulpectomy is preferred to CH for
      the treatment of infected pulps in primary molars.

PMID- 15471520
TI  - Lack of effect of fluoride releasing resin modified glass ionomer restorations on
      the contacting surface of adjacent primary molars. a clinical prospective study.
AB  - AIM: This prospective, split mouth control study was planned to clinically
      evaluate shown short-term caries protection of glass ionomer cement on tooth
      enamel placed in contact to it, as a result of fluoride release. STUDY DESIGN:
      The sample consisted of 83 children, aged 4-7 years, visiting a private practice
      during the years 1999 and 2000. All subjects met the following criteria: a Class
      II restoration was needed to a maxillary or mandibular primary molar on both
      sides of the mouth, the adjacent molars being radiographically diagnosed as sound
      or with caries in the relative proximal enamel only. METHODS: A resin modified
      glass ionomer restoration (Vitremer, 3M) was placed at the test side chosen by
      chance, while an amalgam or composite restoration was placed at the control side.
      Lesion initiation or progression adjacent to each restoration was categorized in
      5 stages radiographically. STATISTICS: The non-parametric Marginal Homogeneity
      test for paired observations was used. RESULTS: Differences between test and
      control were not statistically significant (p>0.1). Two years after restorations
      were placed bitewings were taken from 36 children (41 pairs of restorations).
      Uncontrolled brushing with fluoride dentifrice was reported. Mean fluoride
      treatments performed were 2.2, initial visit included. Lesion progression was: 14
      pairs--no progression in either side; 9 pairs--equal progression by 1 stage in
      both sides; 9 pairs--progression by 1 stage at test side, no progression at
      control side; 6 pairs--progression by 1 stage at control side, no progression at
      test side; 3 pairs--various other combinations of scores. CONCLUSIONS: Under
      these clinical conditions, fluoride release from Class II Vitremer restorations
      did not affect the rate of caries progression at the adjacent enamel of proximal
      primary teeth.

PMID- 15471521
TI  - Clinical outcomes for Early Childhood Caries (ECC): the influence of salivary
      mutans streptococci levels.
AB  - AIM: To assess the relationship between clinical outcomes for children treated
      for Early Childhood Caries (ECC) and salivary mutans streptococci (MS) levels.
      STUDY DESIGN AND METHODS: The study cohort consisted of 79 children (42 males, 37
      females) treated for ECC, aged from 2.3 to 7.3 years at time of entry. Whole non
      stimulated saliva samples were obtained from each subject prior to dental surgery
      and at 6 mths post dental surgery, by saturating a cotton swab in the saliva
      pooled in the floor of the mouth. Samples were placed into PBS on ice and
      processed within 2 hours. Samples were sonicated, serially diluted and plated
      onto MSB and SBA agar plates, then incubated 48 hours anaerobically; SBA plates
      were incubated an additional 24 hours aerobically. The MS level in each sample
      was expressed as a percentage of the total cultivable flora. The cohort was
      evaluated for new caries lesions at 6 months post dental surgery. Relapse was
      defined as the presence of new smooth surface caries lesions. STATISTICS:
      Comparisons between Relapse (R) and Non-Relapse (NR) groups with respect to
      mutans streptococci levels were performed using Wilcoxon tests. Within group
      comparisons were performed using Wilcoxon signed-rank tests. RESULTS: 57 children
      (72%) returned for the 6 months examination and 21 of these subjects (37%)
      relapsed. No statistically significant difference in median salivary MS levels
      existed between the R (0.20%) and NR (0.033%) groups at baseline (p=0.647) or at
      6 months post dental surgery (R=0.03%; NR=0.01%; p=0.273). A statistically
      significant difference between baseline and 6 months post dental surgery was
      noted in the median salivary MS level within the R group (p=0.0007) and within
      the NR group (P<0.0001). CONCLUSIONS: The relapse rate (37%) was high and rapid
      for children treated for ECC. Dental surgery resulted in a statistically
      significant reduction in salivary MS reservoirs for children treated for ECC.
      However, this did not translate into acceptable clinical outcomes.

PMID- 15471522
TI  - Effect of information on dental anxiety and behaviour ratings in children.
AB  - AIM: To establish the effect of information received about dental care on the
      anxiety level of the child prior to receiving any form of dental treatment and on
      their behaviour during dental treatment. METHODS: Eighty-four healthy child
      patients at their first dental visit, between the ages of 8 and 13 years
      attending a paediatric dental clinic in Nigeria participated in the study.
      Information on their dental anxiety level was collected using the Dental Subscale
      of the Child Fear Survey Schedule. The children were asked to identify their
      source and type of dental information received. The information given was later
      categorised into positive or negative for analysis purposes. The children's
      behaviour during dental treatment was assessed using Venham's clinical ratings of
      anxiety and cooperative behaviour. The mean dental anxiety scores, as well as the
      mean Venham behavioural ratings, of those that had received information on dental
      treatment were compared with those that had never received any information.
      RESULTS: Previously received information did not appear to have any significant
      impact on the measures of the dental anxiety level of these children neither was
      there a statistically significant association between information received and
      behaviour of the child in the dental chair. CONCLUSION: Past information may play
      only a minor role in affecting dental anxiety levels and behaviour of the child
      during dental treatment.

PMID- 15471523
TI  - Relationship between lip position and drooling in children with cerebral palsy.
AB  - AIM: This was to determine whether there is any relationship between lip position
      and drooling in children with cerebral palsy (CP). METHODS: One hundred and sixty
      individuals with CP (aged 4-18 years) agreed to take part in the study. The
      following data were collected in two ways. Firstly the presence or absence of
      drooling, the dental age, the incisal relationship and lip position were obtained
      by direct observation of the children. Secondly other data for age, sex, learning
      disability and type of CP were collected using a questionnaire/form. STATISTICS:
      This was by simple Chi squared analysis. RESULTS: A significantly greater number
      of CP children who drooled had incompetent lips (p<0.002). When comparing CP
      children with drooling (mild + moderate + severe) and those without drooling
      there was a clear difference in distribution of it between those with and those
      without competent lips. This difference was found to be highly significant
      (p<0.005). CONCLUSION: Lip position and oral seal share a potentially important
      association with drooling.

PMID- 15471524
TI  - Comparison of diagnostic yields of clinical and radiographic caries examinations
      in children of different age.
AB  - AIM: This was to investigate if the pattern of distribution of caries lesions
      detected by clinical and radiographic examinations at different diagnostic
      thresholds changed over a 3-year period during the course of eruption of the
      permanent dentition. It has been hypothesized that the contribution of bitewing
      radiography to caries detection in posterior teeth may increase when approximal
      contacts are established during maturation of the dentition. METHODS: Clinical
      and radiographic caries recordings were made using the non- cavitated/enamel and
      cavity/dentine thresholds for caries detection among a group of 12-year-old
      Lithuanian children with a high caries experience. Examinations were repeated in
      the same children after 3 years. The bitewing radiographs from both examination
      sessions were coded to ensure unbiased recordings and were read by a single
      examiner. RESULTS: The diagnostic yields of the clinical and radiographic
      examination methods did not change after the permanent teeth had fully erupted.
      At both examination sessions the clinical examination resulted in the detection
      of significantly more lesions than did the radiographic method at the non
      cavitated level (43- 47% lesions detected by clinical means only and 2-26% by
      radiographic means only). Only for approximal surfaces at the cavity/dentine
      diagnostic threshold did radiographs contribute to more lesions (15-16% lesions
      detected by clinical means only and 38-41% by radiographic means only).
      Establishment of approximal contacts in the permanent dentition did not increase
      the relative diagnostic yields of bite-wing radiography in this study group.
      CONCLUSION: The contribution of the two methods to caries diagnosis depends more
      on the diagnostic threshold selected than on the stage of maturation of the
      dentition.

PMID- 15471525
TI  - A logbook for continuous self-assessment during 1 year in paediatric dentistry.
AB  - AIM: The present study was designed to investigate whether a logbook helps
      undergraduate students to develop the ability to self-reflect and to increase
      their self-awareness. METHODS: A logbook was introduced to 54 dental students in
      their fourth year of education at the beginning of the paediatric dentistry
      course. The students filled in a questionnaire on learning styles at the start of
      the course and after 12 months. RESULTS: The results showed that at the end of
      the course significantly fewer students wished to be given detailed instructions
      to solve problems. Significantly more students felt able to expose both their
      weaknesses and strengths in clinical competence in the presence of their
      teachers. Students who reported a good knowledge of their own clinical skills
      found feedback from instructors more constructive compared with those who
      reported less good knowledge. CONCLUSION: For a large group of students, the
      logbook stimulated self-reflection, learning from personal clinical experience,
      and an increase in knowledge about their weaknesses and strengths in clinical
      competence.

PMID- 15471526
TI  - Dental Discomfort Questionnaire: predicting toothache in preverbal children.
AB  - AIM: In the present study the value of the Dental Discomfort Questionnaire in
      predicting toothache in young children is analysed. METHODS: The Dental
      Discomfort Questionnaire (DDQ-8; Cronbach's alpha 0.75) was completed by parents
      on behalf of their children (N=99; mean age 47 months). Half of the children were
      referred to a special dental care centre and the other half were controls from a
      day care centre. RESULTS: The behaviours from the DDQ-8 appeared to be more often
      present in those children with decayed teeth and toothache than in those without
      decayed teeth or toothache. A score of 3 or higher on the DDQ-8 seemed the best
      cut-off point to predict toothache in children. The receiver operating
      characteristic curve (ROC) showed that the DDQ-8 has predictive value for
      toothache. STATISTICS: The validity of the DDQ-8 was expressed as sensitivity,
      specificity and positive predictive value and negative predictive value. The
      DDQ's ability to discriminate between patients with and without toothache was
      estimated by the area under the ROC area of the questionnaire. CONCLUSIONS: The
      DDQ-8 could be helpful for parents, non-dental healthcare workers and researchers
      in predicting the existence of toothache in preverbal children.

PMID- 15471527
TI  - Case report: severe infraocclusion ankylosis occurring in siblings.
AB  - AIM: This was to report a rare case of strong familiar tendency of ankylosis of
      maxillary second primary molars. CASE REPORT: Three Caucasian children, male
      twins of 8.5 years and a sister of 10 years, were diagnosed as having severely
      infraccluded maxillary second primary molars with underlying second premolars. In
      all three cases, the early extraction of the infraoccluded molars and an active
      treatment with cervical extraoral traction allowed the physiologic eruption of
      second premolars. Follow-up showed that normal vertical relationship and bone
      height had been obtained. CONCLUSION: Early diagnosis, as well as appropriate
      treatment and careful follow-up are very important in the presence of severe
      infraocclusion, when the marginal ridge of affected primary teeth is at or below
      gingival level.

PMID- 15471528
TI  - EAPD guidelines for the use of pit and fissure sealants.

PMID- 15471529
TI  - Natural history of plague: perspectives from more than a century of research.
AB  - For more than a century, scientists have investigated the natural history of
      plague, a highly fatal disease caused by infection with the gram-negative
      bacterium Yersinia pestis. Among their most important discoveries were the
      zoonotic nature of the disease and that plague exists in natural cycles involving
      transmission between rodent hosts and flea vectors. Other significant findings
      include those on the evolution of Y. pestis; geographic variation among plague
      strains; the dynamics and maintenance of transmission cycles; mechanisms by which
      fleas transmit Y. pestis; resistance and susceptibility among plague hosts; the
      structure and typology of natural foci; and how landscape features influence the
      focality, maintenance, and spread of the disease. The knowledge gained from these
      studies is essential for the development of effective prevention and control
      strategies.

PMID- 15471530
TI  - Evolutionary ecology of insect immune defenses.
AB  - Evolutionary ecology seeks to understand the selective reasons for the design
      features of the immune defense, especially with respect to parasitism. The
      molecular processes thereby set limitations, such as the failure to recognize an
      antigen, response specificity, the cost of defense, and the risk of autoimmunity.
      Sex, resource availability, and interference by parasites also affect a response.
      In turn, the defense repertoire consists of different kinds of immune responses-
      constitutive or induced, general or specific--and involves memory and lasting
      protection. Because the situation often defies intuition, mathematical analysis
      is typically required to identify the costs and benefits of variation in design,
      but such studies are few. In all, insect immune defense is much more similar to
      that of vertebrates than previously thought. In addition, the field is now
      rapidly becoming revolutionized by molecular data and methods that allow
      unprecedented access to study evolution in action.

PMID- 15471531
TI  - Fecal residues of veterinary parasiticides: nontarget effects in the pasture
      environment.
AB  - Residues of veterinary parasiticides in dung of treated livestock have nontarget
      effects on dung-breeding insects and dung degradation. Here, we review the nature
      and extent of these effects, examine the potential risks associated with
      different classes of chemicals, and describe how greater awareness of these
      nontarget effects has resulted in regulatory changes in the registration of
      veterinary products.

PMID- 15471532
TI  - Mechanisms of hopperburn: an overview of insect taxonomy, behavior, and
      physiology.
AB  - Hopperburn is a non-contagious disease of plants caused by the direct feeding
      damage of certain leafhoppers and planthoppers. Although long studied, especially
      with Empoasca spp. leafhoppers (Cicadellidae: Typhlocybinae), the mechanisms
      underlying hopperburn have only recently been elucidated. Hopperburn is caused by
      a dynamic interaction between complex insect feeding stimuli (termed hopperburn
      initiation) and complex plant responses (termed the hopperburn cascade). Herein
      we review the nature of the feeding stimuli in hopperburn initiation, especially
      for Empoasca spp., which we also compare with the planthopper Nilaparvata lugens.
      Contrary to previous reports, Empoasca hopperburn is not caused solely by toxic
      saliva. Instead, it is caused by a plant wound response triggered by a unique
      type of stylet movement, which is then exacerbated by saliva. Electrical
      penetration graph monitoring has revealed that all Empoasca spp. are cell rupture
      feeders, not sheath feeders, and that certain tactics of that feeding strategy
      are more damaging than others. Measuring the proportions of the most damaging
      feeding led to development of a resistance index, the Stylet Penetration Index,
      which can predict hopperburn severity in different plants or under different
      environmental conditions and can supplement or replace traditional, field-based
      resistance indices.

PMID- 15471534
TI  - Hepatic fibrosis: molecular mechanisms and drug targets.
AB  - Liver fibrosis is the common response to chronic liver injury, ultimately leading
      to cirrhosis and its complications, portal hypertension, liver failure, and
      hepatocellular carcinoma. Efficient and well-tolerated antifibrotic drugs are
      currently lacking, and current treatment of hepatic fibrosis is limited to
      withdrawal of the noxious agent. Efforts over the past decade have mainly focused
      on fibrogenic cells generating the scarring response, although promising data on
      inhibition of parenchymal injury and/or reduction of liver inflammation have also
      been obtained. A large number of approaches have been validated in culture
      studies and in animal models, and several clinical trials are underway or
      anticipated for a growing number of molecules. This review highlights recent
      advances in the molecular mechanisms of liver fibrosis and discusses
      mechanistically based strategies that have recently emerged.

PMID- 15471539
TI  - Characterization of the molecular forms of glutathione S-transferase P1 in human
      gastric cancer cells (Kato III) and in normal human erythrocytes.
AB  - GSTP1 (glutathione S-transferase pi) is involved in stress responses and in
      cellular proliferation pathways as an inhibitor of JNK (c-Jun N-terminal kinase).
      It has been proposed that monomeric GSTP1 functions as a JNK inhibitor. All of
      the studies to date have been performed using rodent cells, and it is unclear if
      monomeric GSTP1 exists in human cells. Monomeric GSTP1 was sought in human
      gastric cancer cells (Kato III) and in normal human erythrocytes using gel
      filtration, ELISA and Western blots. Monomeric GSTP1 was found in conditioned
      medium, in cytosol of Kato III cells and in cytosol of erythrocytes. GSTP1
      subunits from Kato III cells and erythrocytes were heterogeneous when analysed by
      MALDI-TOF (matrix-assisted laser-desorption ionization-time-of-flight) MS,
      suggesting that there were post-translational modifications to GSTP1. One post
      translational modification, phosphorylation of a serine residue in the C-terminal
      portion of GSTP1 where JNK binds, was identified in GSTP1 purified from Kato III
      cells, but not in GSTP1 purified from human erythrocytes. Therefore normal and
      malignant human cells contain GSTP1 monomers with post-translational
      modifications, and it is likely that GSTP1 monomers regulate JNK activity in
      human cells in the same manner as in rodent cells.

PMID- 15471540
TI  - The pivotal role of cholesterol absorption inhibitors in the management of
      dyslipidemia.
AB  - Elevated low-density lipoprotein (LDL)-cholesterol is associated with a
      significantly increased risk of coronary heart disease. Ezetimibe is the first
      member of a new class of selective cholesterol absorption inhibitors. It impairs
      the intestinal reabsorption of both dietary and hepatically excreted biliary
      cholesterol. Ezetimibe is an effective and safe agent for lowering LDL-C and non
      HDL-C. Short term clinical trials have established the role of ezetimibe
      monotherapy and its use in combination with statins. Furthermore, ezetimibe and
      statin combination therapy increased the percentage of patients who achieved
      their LDL-C treatment goal. Studies using surrogate markers of atherosclerosis
      have suggested a possible role of ezetimibe in combating atherosclerosis.
      Ezetimibe provides an effective therapeutic strategy for the management of
      homozygous familial hypercholesterolemia (HoFH) and sitosterolemia. The lack of
      outcomes and long term safety data is attributed to the relatively recent
      introduction of this medication.

PMID- 15471541
TI  - Tools for loading MEDLINE into a local relational database.
AB  - BACKGROUND: Researchers who use MEDLINE for text mining, information extraction,
      or natural language processing may benefit from having a copy of MEDLINE that
      they can manage locally. The National Library of Medicine (NLM) distributes
      MEDLINE in eXtensible Markup Language (XML)-formatted text files, but it is
      difficult to query MEDLINE in that format. We have developed software tools to
      parse the MEDLINE data files and load their contents into a relational database.
      Although the task is conceptually straightforward, the size and scope of MEDLINE
      make the task nontrivial. Given the increasing importance of text analysis in
      biology and medicine, we believe a local installation of MEDLINE will provide
      helpful computing infrastructure for researchers. RESULTS: We developed three
      software packages that parse and load MEDLINE, and ran each package to install
      separate instances of the MEDLINE database. For each installation, we collected
      data on loading time and disk-space utilization to provide examples of the
      process in different settings. Settings differed in terms of commercial database
      management system (IBM DB2 or Oracle 9i), processor (Intel or Sun), programming
      language of installation software (Java or Perl), and methods employed in
      different versions of the software. The loading times for the three installations
      were 76 hours, 196 hours, and 132 hours, and disk-space utilization was 46.3 GB,
      37.7 GB, and 31.6 GB, respectively. Loading times varied due to a variety of
      differences among the systems. Loading time also depended on whether data were
      written to intermediate files or not, and on whether input files were processed
      in sequence or in parallel. Disk-space utilization depended on the number of
      MEDLINE files processed, amount of indexing, and whether abstracts were stored as
      character large objects or truncated. CONCLUSIONS: Relational database (RDBMS)
      technology supports indexing and querying of very large datasets, and can
      accommodate a locally stored version of MEDLINE. RDBMS systems support a wide
      range of queries and facilitate certain tasks that are not directly supported by
      the application programming interface to PubMed. Because there is variation in
      hardware, software, and network infrastructures across sites, we cannot predict
      the exact time required for a user to load MEDLINE, but our results suggest that
      performance of the software is reasonable. Our database schemas and conversion
      software are publicly available at http://biotext.berkeley.edu.

PMID- 15471542
TI  - An unusual case of an ulcerative colitis flare resulting in disseminated
      intravascular coagulopathy and a bladder hematoma: a case report.
AB  - BACKGROUND: Disorders of coagulation have long been associated with inflammatory
      bowel disease. Children, as well as adults, with both active and inactive
      ulcerative colitis have been found to have abnormal coagulation and fibrinolysis.
      Disseminated intravascular coagulation arises from an overwhelming of the
      haemostatic regulatory mechanisms leading to an excessive generation of thrombin
      and a failure of the normal inhibitory pathways to prevent systemic effects of
      this enzyme. Ulcerative colitis has been associated with disseminated
      intravascular coagulation in conjunction with septicemia, toxic megacolon and
      surgery. CASE PRESENTATION: A fourteen-year-old boy with a history of poorly
      controlled ulcerative colitis presented with nonbilious emesis, hematochezia, and
      hematuria. Laboratory workup revealed disseminated intravascular coagulation. He
      was placed on triple antibiotics therapy. An infectious workup came back
      negative. A computerized tomography (CT) scan of the abdomen revealed a marked
      thickening and irregularity of the bladder wall as well as wall thickening of the
      rectosigmoid, ascending, transverse, and descending colon. Patient's clinical
      status remained stable despite a worsening of laboratory values associated with
      disseminated intravascular coagulation. Patient was begun on high dose
      intravenous steroids with improvement of the disseminated intravascular
      coagulation laboratory values within 12 hours and resolution of disseminated
      intravascular coagulopathy within 4 days. A thorough infectious workup revealed
      no other causes to his disseminated intravascular coagulation. CONCLUSIONS: The
      spectrum of hypercoagulable states associated with ulcerative colitis varies from
      mild to severe. Although disseminated intravascular coagulation associated with
      ulcerative colitis is usually related to septicemia, toxic megacolon or surgery,
      we present a case of an ulcerative colitis flare resulting in disseminated
      intravascular coagulation and a bladder hematoma.

PMID- 15471543
TI  - Cloning of a novel inhibin alpha cDNA from rhesus monkey testis.
AB  - BACKGROUND: Inhibins are dimeric gonadal protein hormones that negatively
      regulate pituitary FSH synthesis and secretion. Inhibin B is produced by
      testicular Sertoli cells and is the primary circulating form of inhibin in most
      adult male mammals. Inhibin B is comprised of the inhibin alpha subunit disulfide
      linked to the inhibin/activin betaB subunit. Here we describe the cloning of the
      cDNAs encoding these subunits from adult rhesus monkey testis RNA. METHODS: The
      subunit cDNAs were cloned by a combination of reverse transcriptase polymerase
      chain reaction (RT-PCR) and 5' rapid amplification of cDNA ends (RACE) RT-PCR
      from adult rhesus monkey testis RNA. RESULTS: Both the inhibin alpha and betaB
      subunit nucleotide and predicted protein sequences are highly conserved with
      other mammalian species, particularly with humans. During the course of these
      investigations, a novel inhibin alpha mRNA isoform was also identified. This
      form, referred to as rhesus monkey inhibin alpha-variant 2, appears to derive
      from both alternative transcription initiation as well as alternative splicing.
      rmInhibin alpha-variant 2 is comprised of a novel 5' exon (exon 0), which is
      spliced in-frame with exon 2 of the conventional inhibin alpha isoforms (variant
      1). Exon 1 is skipped in its entirety such that the pro-alpha and part of the
      alpha N regions are not included in the predicted protein. rmInhibin alpha
      variant 2 is of relatively low abundance and its biological function has not yet
      been ascertained. CONCLUSION: The data show that the predicted inhibin B protein
      is very similar between monkeys and humans. Therefore, studies in monkeys using
      recombinant human inhibins are likely to reflect actions of the homologous
      ligands. In addition, we have observed the first inhibin alpha subunit mRNA
      variant. It is possible that variants will be observed in other species as well
      and this may lead to novel insights into inhibin action.

PMID- 15471544
TI  - Gene expression profiling of epithelial ovarian tumours correlated with malignant
      potential.
AB  - BACKGROUND: Epithelial ovarian tumours exhibit a range of malignant potential,
      presenting distinct clinical phenotypes. Improved knowledge of gene expression
      changes and functional pathways associated with these clinical phenotypes may
      lead to new treatment targets, markers for early detection and a better
      understanding of disease progression. RESULTS: Gene expression profiling
      (Affymetrix, U95Av2) was carried out on 18 ovarian tumours including benign
      adenomas, borderline adenocarcinomas of low malignant potential and malignant
      adenocarcinomas. Clustering the expression profiles of samples from patients not
      treated with chemotherapy prior to surgery effectively classified 92% of samples
      into their proper histopathological group. Some cancer samples from patients
      treated with chemotherapy prior to surgery clustered with the benign adenomas.
      Chemotherapy patients whose tumours exhibited benign-like expression patterns
      remained disease free for the duration of this study as indicated by continued
      normal serum CA-125 levels. Statistical analysis identified 163 differentially
      expressed genes: 61 genes under-expressed in cancer and 102 genes over-expressed
      in cancer. Profiling the functional categories of co-ordinately expressed genes
      within this list revealed significant correlation between increased malignant
      potential and loss of both IGF binding proteins and cell adhesion molecules.
      Interestingly, in several instances co-ordinately expressed genes sharing
      biological function also shared chromosomal location. CONCLUSION: Our findings
      indicate that gene expression profiling can reliably distinguish between benign
      and malignant ovarian tumours. Expression profiles of samples from patients pre
      treated with chemotherapy may be useful in predicting disease free survival and
      the likelihood of recurrence. Loss of expression of IGF binding proteins as well
      as specific cell adhesion molecules may be a significant mechanism of disease
      progression in ovarian cancer. Expression levels in borderline tumours were
      intermediate between benign adenomas and malignant adenocarcinomas for a
      significant portion of the differentially expressed genes, suggesting that
      borderline tumours are a transitional state between benign and malignant tumours.
      Finally, genes displaying coordinated changes in gene expression were often
      genetically linked, suggesting that changes in expression for these genes are the
      consequence of regional duplications, deletions or epigenetic events.

PMID- 15471545
TI  - Oxytocin and cholecystokinin secretion in women with colectomy.
AB  - BACKGROUND: Cholecystokinin (CCK) concentrations in plasma have been shown to be
      significantly higher in colectomised subjects compared to healthy controls. This
      has been ascribed to reduced inhibition of CCK release from colon. In an earlier
      study CCK in all but one woman who was colectomised, induced release of oxytocin,
      a peptide present throughout the gastrointestinal (GI) tract. The aim of this
      study was thus to examine if colectomised women had a different oxytocin response
      to CCK compared to healthy controls. METHODS: Eleven women, mean age 34.4 +/- 2.3
      years, who had undergone colectomy because of ulcerative colitis or constipation
      were studied. Eleven age-matched healthy women served as controls. All subjects
      were fasted overnight and given 0.2 microg/kg body weight of CCK-8 i.v. in the
      morning. Samples were taken ten minutes and immediately before the injection, and
      10, 20, 30, 45, 60, 90 and 120 min afterwards. Plasma was collected for
      measurement of CCK and oxytocin concentrations. RESULTS: The basal oxytocin and
      CCK concentrations in plasma were similar in the two groups. Intravenous
      injection of CCK increased the release of oxytocin from 1.31 +/- 0.12 and 1.64 +/
      0.19 pmol/l to 2.82 +/- 0.35 and 3.26 +/- 0.50 pmol/l in controls and
      colectomised women, respectively (p < 0.001). Given the short half-life of CCK-8
      in plasma, the increased concentration following injection could not be
      demonstrated in the controls. On the other hand, in colectomised women, an
      increase of CCK in plasma was observed for up to 20 minutes after the injection,
      concentrations increasing from 1.00 +/- 0.21 to a maximum of 1.81 +/- 0.26 pmol/l
      (p < 0.002). CONCLUSION: CCK stimulates the release of oxytocin in women. There
      is no difference in plasma concentrations between colectomised and controls.
      However, colectomy seems to reduce the metabolic clearance of CCK. The
      hyperCCKemia in patients who had undergone colectomy is consequently not only
      dependent on CCK release, but may also depend on reduced clearance.

PMID- 15471546
TI  - Branched-chain amino acid aminotransferase and methionine formation in
      Mycobacterium tuberculosis.
AB  - BACKGROUND: Tuberculosis remains a major world-wide health threat which demands
      the discovery and characterisation of new drug targets in order to develop future
      antimycobacterials. The regeneration of methionine consumed during polyamine
      biosynthesis is an important pathway present in many microorganisms. The final
      step of this pathway, the conversion of ketomethiobutyrate to methionine, can be
      performed by aspartate, tyrosine, or branched-chain amino acid aminotransferases
      depending on the particular species examined. RESULTS: The gene encoding for
      branched-chain amino acid aminotransferase in Mycobacterium tuberculosis H37Rv
      has been cloned, expressed, and characterised. The enzyme was found to be a
      member of the aminotransferase IIIa subfamily, and closely related to the
      corresponding aminotransferase in Bacillus subtilis, but not to that found in B.
      anthracis or B. cereus. The amino donor preference for the formation of
      methionine from ketomethiobutyrate was for isoleucine, leucine, valine,
      glutamate, and phenylalanine. The enzyme catalysed branched-chain amino acid and
      ketomethiobutyrate transamination with a Km of 1.77 - 7.44 mM and a Vmax of 2.17 
      5.70 micromol/min/mg protein, and transamination of ketoglutarate with a Km of
      5.79 - 6.95 mM and a Vmax of 11.82 - 14.35 micromol/min/mg protein. Aminooxy
      compounds were examined as potential enzyme inhibitors, with O
      benzylhydroxylamine, O-t-butylhydroxylamine, carboxymethoxylamine, and O
      allylhydroxylamine yielding mixed-type inhibition with Ki values of 8.20 - 21.61
      microM. These same compounds were examined as antimycobacterial agents against M.
      tuberculosis and a lower biohazard M. marinum model system, and were found to
      completely prevent cell growth. O-Allylhydroxylamine was the most effective
      growth inhibitor with an MIC of 78 microM against M. marinum and one of 156
      microM against M. tuberculosis. CONCLUSION: Methionine formation from
      ketomethiobutyrate is catalysed by a branched-chain amino acid aminotransferase
      in M. tuberculosis. This enzyme can be inhibited by selected aminooxy compounds,
      which also have effectiveness in preventing cell growth in culture. These
      compounds represent a starting point for the synthesis of branched-chain
      aminotransferase inhibitors with higher activity and lower toxicity.

PMID- 15471547
TI  - Extending the mutual information measure to rank inferred literature
      relationships.
AB  - BACKGROUND: Within the peer-reviewed literature, associations between two things
      are not always recognized until commonalities between them become apparent. These
      commonalities can provide justification for the inference of a new relationship
      where none was previously known, and are the basis of most observation-based
      hypothesis formation. It has been shown that the crux of the problem is not
      finding inferable associations, which are extraordinarily abundant given the
      scale-free networks that arise from literature-based associations, but
      determining which ones are informative. The Mutual Information Measure (MIM) is a
      well-established method to measure how informative an association is, but is
      limited to direct (i.e. observable) associations. RESULTS: Herein, we attempt to
      extend the calculation of mutual information to indirect (i.e. inferable)
      associations by using the MIM of shared associations. Objects of general research
      interest (e.g. genes, diseases, phenotypes, drugs, ontology categories) found
      within MEDLINE are used to create a network of associations for evaluation.
      CONCLUSIONS: Mutual information calculations can be effectively extended into
      implied relationships and a significance cutoff estimated from analysis of random
      word networks. Of the models tested, the shared minimum MIM (MMIM) model is found
      to correlate best with the observed strength and frequency of known associations.
      Using three test cases, the MMIM method tends to rank more specific relationships
      higher than counting the number of shared relationships within a network.

PMID- 15471549
TI  - Patterns of Schistosoma haematobium infection, impact of praziquantel treatment
      and re-infection after treatment in a cohort of schoolchildren from rural KwaZulu
      Natal/South Africa.
AB  - BACKGROUND: Schistosomiasis is one of the major health problems in tropical and
      sub-tropical countries, with school age children usually being the most affected
      group. In 1998 the Department of Health of the province of KwaZulu-Natal
      established a pilot programme for helminth control that aimed at regularly
      treating primary school children for schistosome and intestinal helminth
      infections. This article describes the baseline situation and the impact of
      treatment on S. haematobium infection in a cohort of schoolchildren attending
      grade 3 in a rural part of the province. METHODS: Primary schoolchildren from
      Maputaland in northern KwaZulu-Natal were examined for Schistosoma haematobium
      infection, treated with praziquantel and re-examined four times over one year
      after treatment in order to assess the impact of treatment and patterns of
      infection and re-infection. RESULTS: Praziquantel treatment was highly
      efficacious at three weeks after treatment when judged by egg reduction rate
      (95.3%) and cure rate of heavy infections (94.1%). The apparent overall cure rate
      three weeks after treatment (57.9%) was much lower but improved to 80.7% at 41
      weeks after treatment. Re-infection with S. haematobium was low and appeared to
      be limited to the hot and rainy summer. Analysis of only one urine specimen per
      child considerably underestimated prevalence when compared to the analysis of two
      specimens, but both approaches provided similar estimates of the proportion of
      heavy infections and of average infection intensity in the population.
      CONCLUSION: According to WHO guidelines the high prevalence and intensity of S.
      haematobium infection necessitate regular treatment of schoolchildren in the
      area. The seasonal transmission pattern together with the slow pace of re
      infection suggest that one treatment per year, applied after the end of summer,
      is sufficient to keep S. haematobium infection in the area at low levels.

PMID- 15471548
TI  - CD155/PVR plays a key role in cell motility during tumor cell invasion and
      migration.
AB  - BACKGROUND: Invasion is an important early step of cancer metastasis that is not
      well understood. Developing therapeutics to limit metastasis requires the
      identification and validation of candidate proteins necessary for invasion and
      migration. METHODS: We developed a functional proteomic screen to identify
      mediators of tumor cell invasion. This screen couples Fluorophore Assisted Light
      Inactivation (FALI) to a scFv antibody library to systematically inactivate
      surface proteins expressed by human fibrosarcoma cells followed by a high
      throughput assessment of transwell invasion. RESULTS: Using this screen, we have
      identified CD155 (the poliovirus receptor) as a mediator of tumor cell invasion
      through its role in migration. Knockdown of CD155 by FALI or by RNAi resulted in
      a significant decrease in transwell migration of HT1080 fibrosarcoma cells
      towards a serum chemoattractant. CD155 was found to be highly expressed in
      multiple cancer cell lines and primary tumors including glioblastoma (GBM).
      Knockdown of CD155 also decreased migration of U87MG GBM cells. CD155 is
      recruited to the leading edge of migrating cells where it colocalizes with actin
      and alphav-integrin, known mediators of motility and adhesion. Knockdown of CD155
      also altered cellular morphology, resulting in cells that were larger and more
      elongated than controls when plated on a Matrigel substrate. CONCLUSION: These
      results implicate a role for CD155 in mediating tumor cell invasion and migration
      and suggest that CD155 may contribute to tumorigenesis.

PMID- 15471550
TI  - A step ahead: combining protein purification and correct folding selection.
AB  - The success of recombinant protein expression seems unpredictable and even good
      yields of soluble proteins do not guarantee the correct folding. The search for
      soluble constructs can be performed by exploiting libraries and speeded up by
      automation, but these approaches are money and time consuming and the tags used
      for affinity purification can mask the real stability of the target proteins. The
      ideal purification protocol would include the structure quality control. A recent
      paper commented in this article describes a phage-display method to screen for
      antibodies that are able to re-fold after heat-denaturation and can be
      selectively affinity-purified only if monodispersed. It turned out that the
      proteins with high recovery performance after heat-shock were also suitable for
      efficient recombinant expression.

PMID- 15471552
TI  - Association of mitral annulus calcification, aortic valve calcification with
      carotid intima media thickness.
AB  - BACKGROUND: Mitral annular calcification (MAC) and aortic annular calcification
      (AVC) may represent a manifestation of generalized atherosclerosis in the
      elderly. Alterations in vascular structure, as indexed by the intima media
      thickness (IMT), are also recognized as independent predictors of adverse
      cardiovascular outcomes. AIM: To examine the relationship between the degree of
      calcification at mitral and/or aortic valve annulus and large artery structure
      (thickness). METHODS: We evaluated 102 consecutive patients who underwent
      transthoracic echocardiography and carotid artery echoDoppler for various
      indications; variables measured were: systemic blood pressure (BP), pulse
      pressure (PP=SBP-DBP), body mass index (BMI), fasting glucose, total, HDL, LDL
      chlolesterol, triglycerides, cIMT. The patients were divided according to a
      grading of valvular/annular lesions independent scores based on acoustic
      densitometry: 1 = annular/valvular sclerosis/calcification absence; 2 =
      annular/valvular sclerosis; 3 = annular calcification; 4 = annular-valvular
      calcification; 5 = valvular calcification with no recognition of the leaflets.
      RESULTS: Patient score was the highest observed for either valvular/annulus. Mean
      cIMT increased linearly with increasing valvular calcification score, ranging
      from 3.9 +/- 0.48 mm in controls to 12.9 +/- 1.8 mm in those subjects scored 5 (p
      < 0.0001). In the first to fourth quartile of cIMT values the respective maximal
      percentual of score were: score 1: 76.1%, score 2: 70.1%, score 4: 54.3% and
      score 5: 69.5% (p > 0.0001). CONCLUSION: MAC and AVC score can identify subgroups
      of patients with different cIMT values which indicate different incidence and
      prevalence of systemic artery diseases. This data may confirm MAC-AVC as a useful
      important diagnostic parameter of systemic atherosclerotic disease.

PMID- 15471551
TI  - Intracardiac echocardiography to guide transseptal catheterization for
      radiofrequency catheter ablation of left-sided accessory pathways: two case
      reports.
AB  - Intracardiac echocardiography (ICE) is a useful tool for guiding transseptal
      puncture during electrophysiological mapping and ablation procedures. Left-sided
      accessory pathways (LSAP) can be ablated by using two different modalities:
      retrograde approach through the aortic valve and transseptal approach with
      puncture of the fossa ovalis. We shall report two cases of LSAP where
      transcatheter radiofrequency ablation (TCRFA) was firstly attempted via
      transaortic approach with ineffective results. Subsequently, a transseptal
      approach under ICE guidance has been performed. During atrial septal puncture ICE
      was able to locate the needle tip position precisely and provided a clear
      visualization of the "tenting effect" on the fossa ovalis. ICE allowed a better
      mapping of the mitral ring and a more effective catheter ablation manipulation
      and tip contact which resulted in a persistent and complete ablation of the
      accessory pathway with a shorter time of fluoroscopic exposure. ICE-guided
      transseptal approach might be a promising modality for TCRFA of LSAP.

PMID- 15471553
TI  - The critical role of type-1 innate and acquired immunity in tumor immunotherapy.
AB  - The discovery of a large array of tumor antigens has demonstrated that host
      lymphocytes can indeed recognize and destroy tumor cells as originally proposed
      in the cancer immunosurveillance hypothesis. Recent reports that led to the
      cancer immunoediting concept also strongly support the immunosurveillance
      hypothesis, and they further indicate that the host immune system plays a
      critical role not only in promoting host protection against cancer but also in
      selecting tumors that can better escape from immune attack. Thus, it is now clear
      that T cells have the ability to recognize and destroy spontaneously arising
      tumors. However, the generation of antitumor immunity is often difficult in the
      tumor-bearing host because of various negative regulatory mechanisms. Here, we
      review our recent work on tumor immunotherapy, which utilizes the activation of
      type-1 innate and/or acquired immunity as a potent strategy to overcome immunosup
      pression in the tumor-bearing host. We have established a variety of tumor
      therapeutic protocols that aim to activate type-1 immunity, such as tumor-vaccine
      therapy with CpG encapsulat-ed in liposomes, cell therapy using tumor-specific
      Th1 cells, and gene therapy using gene-engineered Th1 cells. We found that CpG
      encapsulated in liposomes stimulated IL-12-producing DC and induced IFN-gamma
      producing NK cells, NKT cells, and tumor-specific CTL. Th1 cell therapy was also
      shown to be beneficial for acceleration of APC/Th1 cell-cell interaction in the
      DLN, which was critical for inducing tumor-specific CTL at the tumor site.
      Therefore, we conclude that the activation of type-1 innate and acquired immunity
      is crucial for tumor immunotherapy in order to overcome strong immunosuppression
      in the tumor-bearing host.

PMID- 15471554
TI  - Genetic and epigenetic factors involved in B-cell lymphomagenesis.
AB  - Malignant lymphomas have been classified by the WHO into disease categories based
      not only on histological features, but also on cell surface markers, cytogenetic
      and clinical features. It is known that chromosome translocation plays an
      important role in lymphoma development, but it is not entirely clear yet why a
      given type of chromosome translocation is associated with a specific type of
      lymphoma. This review deals with molecular mechanisms of B-cell lymphoma
      development in association with chromosome translocations. The outcome of
      chromosome translocations can be categorized into three factors: enhancement of
      proliferation, inhibition of differentiation and anti-apoptotic activity. It is
      well known that chromosome translocation by itself cannot cause cells to become
      malignant because it is only one of the growth advantages leading to malignancy,
      while additional genetic and epigenetic alterations are required for cells to
      become fully malignant. Mucosa-associated lymphoid tissue (MALT) lymphomas of the
      stomach are unique in that a majority can be cured by Helicobacter pylori
      eradication, although 20 to 30% remain resistant. Others as well as we have
      demonstrated that the presence of the API2-MALT1 chimeric gene correlates well
      with resistance to H. pylori eradication treatment. These characteristics have
      led to the speculation that the classification of MALT lymphoma falls somewhere
      between tumor and inflammation. Although MALT lymphoma seems to have unique
      features in comparison with other types of B-cell lymphomas, it shares common
      molecular mechanisms with B-cell lymphoma development.

PMID- 15471556
TI  - c-kit gene mutations in intracranial germinomas.
AB  - Gain-of-function mutations of the c-kit gene and the expression of phosphorylated
      KIT are found in most gastrointestinal stromal tumors and mastocytosis. Further,
      almost all gonadal seminomas/dysgerminomas exhibit KIT membranous staining, and
      several reports have clarified that some (10-25%) have a c-kit gene mutation.
      But, whether intracranial germinomas also have a c-kit gene mutation remains
      unsolved. To elucidate the presence, frequency, and location of c-kit gene
      mutations in intracranial germinomas, we analyzed five mutational hot spots
      (exons 9, 10, 11, 13, and 17) in the c-kit genomic DNA of 16 germinomas using
      polymerase chain reaction and direct sequencing. We found c-kit gene mutations at
      exon 11 (W557C) or 17 (D816V, D820V, and N822Y) in four germinomas (25.0%),
      although no statistically significant difference in any clinicopathological
      factor was found between patients with or without mutations. These results are
      similar to those seen in gonadal seminoma/dysgerminoma patients, and confirm that
      intracranial germinomas are exact counterparts of gonadal
      seminomas/dysgerminomas, as would be expected on histological and
      immunohistochemical grounds. Moreover, molecular targeting drugs such as imatinib
      mesylate (STI571), which is a selective inhibitor of KIT, might be promising
      agents for the treatment of intracranial germinomas with c-kit gene mutations.

PMID- 15471555
TI  - Estrogen enhancement of androgen-responsive gene expression in hormone-induced
      hyperplasia in the ventral prostate of F344 rats.
AB  - It has been postulated that, in addition to the crucial role of androgens,
      estrogens may be involved in development of prostate hyperplasia and cancer. In
      rats, combined administration of estrogen and androgen synergistically increases
      ventral prostate weight, and continued treatment results in the development of
      glandular hyperplasia. Prostate adenocarcinoma can be induced by chemical
      carcinogens in rats, and estrogen given together with an androgen generally
      shortens the latent period or increases the incidence and/or multiplicity of
      carcinomas. However, the mechanisms responsible for these synergistic effects of
      estrogen and androgen are poorly understood. In the present study, we examined
      the combined effects of 17beta-estradiol (E2) and testosterone (T) on gene
      expression in an early stage of prostate hyperplasia in an F344 rat model.
      ERalpha expression, which has been suggested to contribute to development of
      prostatic hyperplasia, was increased by the combined treatment with T and E2,
      while it was suppressed by T alone. Expression levels of two androgen-responsive
      genes, probasin and kallikrein S3, were increased in the ventral prostate of rats
      treated with T plus E2 for 4 weeks in a dose-dependent manner, while short-term
      treatment did not alter the expression. These results suggested that enhancing
      effects of E2 on transcription of androgen-responsive genes, as well as an
      increased level of ERalpha may play roles in the synergistic effects of E2 on T
      induced prostate hyperplasia.

PMID- 15471557
TI  - Sequential observations on the occurrence of preneoplastic and neoplastic lesions
      in mouse colon treated with azoxymethane and dextran sodium sulfate.
AB  - Previously, we proposed a novel mouse model for colitis-related colon
      carcinogenesis using azoxymethane (AOM) and dextran sodium sulfate (DSS) (Cancer
      Sci 2003; 94: 965-73). In the current study, sequential analysis of pathological
      alterations during carcinogenesis in our model was conducted to establish the
      influence of inflammation caused by DSS on colon carcinogenesis in this model.
      Male ICR mice were given a single intraperitoneal injection of AOM (10 mg/kg body
      weight) and given 2% (w/v) DSS in the drinking water for 7 days, starting 1 week
      after the AOM injection. They were sequentially sacrificed at weeks 2, 3, 4, 5,
      6, 9, 12, and 14 for histopathological and immunohistochemical examinations.
      Colonic adenomas were found in 2 (40% incidence and 0.40 +/- 0.49 multiplicity)
      of 5 mice at week 3 and colon carcinomas developed in 2 (40% incidence and 2.00
      +/- 3.52 multiplicity) of 5 mice at week 4. Their incidence gradually increased
      with time and reached 100% (6.20 +/- 2.48 multiplicity) at week 6. At week 14,
      the multiplicity of adenocarcinoma was 9.75 +/- 2.49 (100% incidence). In
      addition, colonic dysplasia was noted at all time-points. The scores of colonic
      inflammation and nitrotyrosine immunohistochemistry were extremely high at early
      time-points and were well correlated. Our results suggest that combined treatment
      of mice with AOM and DSS generates neoplasms in the colonic mucosa via dysplastic
      lesions induced by nitrosative stress.

PMID- 15471558
TI  - Paradoxically enhanced immunoreactivity of hepatocyte growth factor activator
      inhibitor type 1 (HAI-1) in cancer cells at the invasion front.
AB  - We have previously demonstrated significantly decreased immunoreactivity of
      hepatocyte growth factor activator inhibitor type 1 (HAI-1), an integral membrane
      protein that exhibits potent inhibitory activity against hepatocyte growth factor
      activator (HGFA) and matriptase, in colorectal adenocarcinomas. In this report,
      we describe further detailed analysis of HAI-1 expression in colorectal
      adenocarcinoma by using three kinds of anti-HAI-1 antibodies, each of which
      recognizes a distinct epitope of the HAI-1 molecule, and also by in-situ
      hybridization for HAI-1 mRNA. The results indicated that the decreased
      immunoreactivity of HAI-1 in colorectal carcinoma cells is largely a result of
      enhanced ectodomain shedding of HAI-1 in these cells. In contrast,
      immunoreactivity of mature membrane-form HAI-1 was paradoxically en-hanced in
      cancer cells at the invasion front, showing intense cell-stroma interactions
      and/or sprouting invasion. This finding indicates that these invading cells
      showed decreased ectodomain shedding of HAI-1 and consequently might require the
      existence of the membrane-form HAI-1. Of particular interest was the observation
      of a possible inverse correlation between paradoxical up-regulation of membrane
      form HAI-1 expression and membrane-associated E-cadherin in these cells. These
      membrane-form HAI-1-positive sprouting cancer cells were also negative for MIB-1
      immunohistochemically, indicating a low-proliferating population. All these
      results suggest that HAI-1 may mediate diverse functions in regard to the
      progression of colorectal carcinomas, and the immunoreactivity of membrane-form
      HAI-1 may serve as a marker of invading cancer cells.

PMID- 15471559
TI  - Promoter hypermethylation of DAP-kinase is associated with poor survival in
      primary biliary tract carcinoma patients.
AB  - To clarify the clinicopathological significance of promoter hypermethylation of
      tumor suppressor and tumor-related genes in biliary tract carcinomas, we examined
      the promoter methylation status of multiple genes in primary biliary tract
      carcinomas. These consisted of carcinomas of the bile duct, gallbladder, and
      duodenal ampulla. Surgical specimens were obtained from a total of 37 patients
      with biliary tract carcinoma. The cohort consisted of 23 patients with bile duct
      carcinoma, 9 patients with gallbladder carcinoma, and 5 patients with ampullary
      carcinoma. The methylation status of CHFR, DAP-kinase, E-cadherin, hMLH1, p16,
      RASSF1A, and RUNX3 was examined by methylation-specific polymerase chain reaction
      (MSP). The correlation between methylation status and clinicopathological
      characteristics was then assessed. The methylation frequencies of CHFR, DAP
      kinase, E-cadherin, hMLH1, p16, RASSF1A, and RUNX3 genes were 16.2%, 21.4%,
      27.0%, 8.1%, 24.3%, 27.0%, and 56.8%, respectively, in primary biliary tract
      carcinomas. The number of methylated genes per sample was 2.17 +/- 0.28 (average
      +/- SD) in bile duct carcinomas, 1.80 +/- 0.97 in ampullary carcinomas, and 0.89
      +/- 0.35 in gallbladder carcinomas, with a statistically significant difference
      between bile duct carcinomas and gallbladder carcinomas (P = 0.02). As for
      clinicopathological significance, patients with a methylated RUNX3 promoter were
      significantly older than those with unmethylated RUNX3 (P = 0.01), and DAP-kinase
      methylation was more frequent in poorly differentiated tumors than in well to
      moderately differentiated ones (P = 0.04). The overall survival rate was
      significantly lower in patients with methylated DAP-kinase (P = 0.009) or RUNX3
      (P = 0.034) compared to those with unmethylated genes. Furthermore, DAP-kinase
      methylation-positive status was independently associated with poor survival in
      multivariate analyses (hazard ratio = 8.71, P = 0.024). A significant proportion
      of primary biliary tract carcinomas exhibited promoter hypermethylation of tumor
      suppressor and tumor-related genes, although bile duct carcinomas are more prone
      to being affected by promoter methylation than are gallbladder carcinomas.
      Hypermethylation of DAP-kinase appears to be a significant prognostic factor in
      primary biliary tract carcinomas.

PMID- 15471560
TI  - Methylation-associated silencing of the Wnt antagonist SFRP1 gene in human
      ovarian cancers.
AB  - The SFRP1 gene on chromosome 8p11.2 encodes a Wnt signaling antagonist, and was
      recently demonstrated to be a new tumor suppressor that is inactivated by
      promoter methylation in human colon cancers. Here, we analyzed promoter
      methylation of the SFRP1 gene in human ovarian cancers, in which loss of
      heterozygosity in 8p is frequently observed and involvement of the Wnt signaling
      pathway has been suggested. Methylation-specific PCR (MSP) analysis showed that
      four of 13 ovarian cancer cell lines and two of 17 primary ovarian cancers had
      methylated SFRP1, while an immortalized ovarian epithelial cell line, HOSE, and
      seven ovarian endometrial cyst samples did not. In the four ovarian cancer cell
      lines with the methylation, SFRP1 was not expressed at all as determined by
      quantitative RT-PCR analysis. A cell line with SFRP1 methylation, MCAS, was
      treated with a demethylating agent, 5-aza-2'-deoxycytidine, and demethylation of
      the promoter and re-expression of SFRP1 were observed. These results show that
      SFRP1 is inactivated by promoter methylation in human ovarian cancers, as well as
      colon cancers.

PMID- 15471561
TI  - Effect of hepatitis C virus infection on the risk of non-Hodgkin's lymphoma: a
      meta-analysis of epidemiological studies.
AB  - Although a high prevalence of hepatitis C virus (HCV) infection among non
      Hodgkin's lymphoma (NHL) patients had been reported, subsequent epidemiological
      studies conducted to examine a causal association between HCV and NHL have
      provided inconsistent results across studies. A strikingly positive association
      has been reported primarily from Italy and Japan, while no association was found
      in other regions of the world. To clarify the association between HCV and NHL, we
      conducted a systematic literature review. Eligible study designs were nested case
      control studies, population-based case-control studies, and hospital-based case
      control studies using non-cancer subjects as controls. The studies published
      through January 1991 to August 2003 were searched through Medline. Ultimately, 23
      studies with 4049 NHL patients and 1,813,480 controls were identified. Summary
      statistics were crude odds ratios (ORs) comparing the anti-HCV seropositive and
      seronegative subjects. As we identified heterogeneity between studies, summary
      statistics were calculated based on a random-effect model. We did not find any
      evidence of publication bias. The major sources of variation were the use of
      blood donor controls and year of publication. The summary OR for NHL was 5.70
      (95% confidence interval (CI), 4.09-7.96, P < 0.001). The subgroup analysis by
      phenotype showed a similar trend for B-cell (5.04, 95% CI: 3.59-7.06) and T-NHL
      (2.51, 95% CI: 1.39-4.56). In conclusion, we found a strongly positive
      association between anti-HCV seropositive test subjects and risk of NHL. Further
      biological studies examining this association are warranted.

PMID- 15471562
TI  - Determinants of sensitivity and resistance to gemcitabine: the roles of human
      equilibrative nucleoside transporter 1 and deoxycytidine kinase in non-small cell
      lung cancer.
AB  - Gemcitabine is one of the most commonly used agents for lung cancer chemotherapy,
      but the determinants of sensitivity and/or resistance to this agent are not yet
      fully understood. In this study we used quantitative RT-PCR to examine the
      expression levels of human equilibrative nucleoside transporter 1 (hENT1) and
      deoxycytidine kinase (dCK) genes in non-small cell lung cancer (NSCLC) cell lines
      in relation to sensitivity and resistance to gemcitabine. The basal expression
      levels of hENT1 were significantly correlated with the IC50 values for
      gemcitabine (r =-0.6769, P = 0.0005), whereas dCK expression levels were not. In
      a highly gemcitabine-sensitive cell line, NCI-H23, the sensitivity to gemcitabine
      was inhibited by nitrobenzylmercaptopurine ribonucleoside (NBMPR), an inhibitor
      of hENT1, without significant modulation of hENT1 expression. These data suggest
      that hENT1 is associated with gemcitabine sensitivity in lung cancer. We also
      continuously exposed NCI-H23 cells to gemcitabine and subsequently established
      the drug-resistant clone H23/GEM-R, which showed a significant decrease of dCK
      expression; however, hENT1 expression was not altered in the continuously exposed
      sublines or in the resistant clone. We conclude that increased hENT1 expression
      is a determinant of gemcitabine sensitivity, while decreased dCK expression is
      associated with acquired resistance to gemcitabine in NSCLC cells. Thus, hENT1
      and dCK might be useful as predictive markers for efficacy of gemcitabine therapy
      in NSCLC.

PMID- 15471563
TI  - Isolation of an anti-angiogenic substance from Agaricus blazei Murill: its
      antitumor and antimetastatic actions.
AB  - We previously found that ergosterol isolated from Agaricus blazei inhibited tumor
      growth through the inhibition of tumor-induced neovascularization. In the present
      study, we isolated further anti-angiogenic substances (A-1 and A-2) from this
      fungus using an assay system of angiogenesis induced by Matrigel supplemented
      with vascular endothelial growth factor, and A-1 was identified as sodium
      pyroglutamate. Next, we examined the antitumor and antimetastatic actions of A-1
      using Lewis lung carcinoma (LLC)-bearing mice. A-1 (30, 100 and 300 mg/kg)
      inhibited tumor growth and metastasis to the lung. The reduction of the numbers
      of splenic lymphocytes, CD4+ and CD8+ T cells in LLC-bearing mice was inhibited
      by the oral administration of A-1 (30, 100 and 300 mg/kg). Further, A-1 increased
      the number of apoptotic cells of tumors and the numbers of CD8+ T and natural
      killer cells invading the tumors, and inhibited the increase of von Willebrand
      factor expression (a measure of angiogenesis) in the tumors. These results
      suggest that the antitumor and antimetastatic actions of A-1 (sodium
      pyroglutamate) may be associated with inhibition of the reduction of immune
      response caused by the tumor growth and tumor-induced neovascularization. This is
      the first report showing that sodium pyroglutamate isolated from A. blazei as an
      anti-angiogenic substance has potent antitumor and antimetastatic actions, as
      well as immune-modulatory activity, in tumor-bearing mice.

PMID- 15471564
TI  - Sonodynamic therapy on chemically induced mammary tumor: pharmacokinetics, tissue
      distribution and sonodynamically induced antitumor effect of porfimer sodium.
AB  - The sonodynamically induced antitumor effect of porfimer sodium (PF) was
      evaluated on a chemically induced mammary tumor in Sprague-Dawley rats. The
      timing of 24 h after the administration of PF was chosen for the ultrasonic
      exposure, based on pharmacokinetic analysis of the PF concentrations in the
      tumor, plasma, skin and muscle. At a PF dose not less than 2.5 mg/kg and at a
      free-field ultrasonic intensity not less than 3 W/cm2, the synergistic effect
      between PF administration and ultrasonic exposure on the tumor growth inhibition
      was significant. The ultrasonic intensity showed a relatively sharp threshold for
      the synergistic antitumor effect, which is typical of an ultrasonic effect
      mediated by acoustic cavitation. These results suggest that PF is a potentially
      useful as a sonosensitizer for sonodynamic treatment of chemically induced
      tumors.

PMID- 15471565
TI  - Activation of human IK and SK Ca2+ -activated K+ channels by NS309 (6,7-dichloro
      1H-indole-2,3-dione 3-oxime).
AB  - We have identified and characterized the compound NS309 (6,7-dichloro-1H-indole
      2,3-dione 3-oxime) as a potent activator of human Ca2+ -activated K+ channels of
      SK and IK types, whereas it is devoid of effect on BK type channels. IK- and SK
      channels have previously been reported to be activated by the benzimidazolinone,
      1-EBIO and more potently by its dichloronated-analogue, DC-EBIO. NS309 is at
      least 1000 times more potent than 1-EBIO and at least 30 times more potent than
      DC-EBIO when the compounds are compared on the same cell.

PMID- 15471566
TI  - Simultaneous probing of hydration and polarity of lipid bilayers with 3
      hydroxyflavone fluorescent dyes.
AB  - The penetration of water into the hydrophobic interior leads to polarity and
      hydration profiles across lipid membranes which are fundamental in the
      maintenance of membrane architecture as well as in transport and insertion
      processes into the membrane. The present paper is an original attempt to evaluate
      simultaneously polarity and hydration properties of lipid bilayers by a
      fluorescence approach. We applied two 3-hydroxyflavone probes anchored in lipid
      bilayers at a relatively precise depth through their attached ammonium groups.
      They are present in two forms: either in H-bond-free form displaying a two-band
      emission due to an excited state intramolecular proton transfer reaction (ESIPT),
      or in H-bonded form displaying a single-band emission with no ESIPT. The
      individual emission profiles of these forms were obtained by deconvolution of the
      probes' fluorescence spectra. The polarity of the probe surrounding the bilayer
      was estimated from the two-band spectra of the H-bond-free form, while the local
      hydration was estimated from the relative contribution of the two forms. Our
      results confirm that by increasing the lipid order (phase transition from fluid
      to gel phase, addition of cholesterol or decrease in the lipid unsaturation), the
      polarity and to a lesser extent, the hydration of the bilayers decrease
      simultaneously. In contrast, when fluidity (i.e. lipid order) is kept invariant,
      increase of temperature and of bilayer curvature leads to a higher bilayer
      hydration with no effect on the polarity. Furthermore, no correlation was found
      between dipole potential and the hydration of the bilayers.

PMID- 15471567
TI  - Different functional roles of arginine residues 39 and 61 and tyrosine residue 98
      in transport and channel mode of the glutamate transporter EAAC1.
AB  - The excitatory amino acid transporter EAAC1 is an electrogenic Na+ - and K+ 
      gradient-driven transporter. In addition, the transporter mediates in the
      presence of Na+ and glutamate an anion conductance uncoupled from the transport
      of the glutamate. The first two N-terminal domains, important for forming the
      conductance mode, are extracellularly bordered by positively charged arginine
      residues, R39 and R61, being completely conserved throughout the transporter
      family. Also the conserved tyrosine residue Y98 could be important for Cl-
      conductance. We have investigated, by measurements of glutamate uptake and
      glutamate-induced currents, the effects of mutation of the arginines and the
      tyrosine to alanine. The mutation R39A hardly affects transport and channel mode.
      The mutation R61A, on the other hand, reduces the activity of transport but
      stimulates the channel conductance. In addition, the apparent Km values for
      glutamate uptake and for the glutamate-activated current are reduced. Glutamate
      stimulation of current seems to be associated with a voltage-dependent step, and
      the apparent valence of charge moved during binding is reduced in the R61A
      mutant. The mutation Y98A leads to reduced function with reduced apparent Km
      value for glutamate, and with strong reduction of the selectivity ration between
      NO3- and Cl- of the conductance mode.

PMID- 15471568
TI  - Influence of lipid chain unsaturation on membrane-bound melittin: a fluorescence
      approach.
AB  - Melittin, a cationic hemolytic peptide, is intrinsically fluorescent due to the
      presence of a single functionally important tryptophan residue. The organization
      of membrane-bound melittin is dependent on the physical state and composition of
      membranes. In particular, polyunsaturated lipids have been shown to modulate the
      membrane-disruptive action of melittin. Phospholipids with polyunsaturated acyl
      chains are known to modulate a number of physical properties of membranes and
      play an important role in regulating structure and function of membrane proteins.
      In this study, we have used melittin to address the influence of unsaturated
      lipids in modulating lipid-protein interactions. Our results show that
      fluorescence parameters such as intensity, emission maximum, polarization,
      lifetime and acrylamide quenching of melittin incorporated in membranes are
      dependent on the degree of unsaturation of lipids in membranes. Importantly,
      melittin in membranes composed of various unsaturated lipids shows red edge
      excitation shift (REES) implying that melittin is localized in a motionally
      restricted region in membranes. The extent of REES was found to increase
      drastically in membranes with increasing unsaturation, especially when the lipids
      contained more than two double bonds. In addition, increasing unsaturation in
      membranes causes a considerable change in the secondary structure of membrane
      bound melittin. Taken together, our results assume significance in the overall
      context of the role of unsaturated lipids in membranes in the organization and
      function of membrane proteins and membrane-active peptides.

PMID- 15471569
TI  - The alphaM1 segment of the nicotinic acetylcholine receptor exhibits
      conformational flexibility in a membrane environment.
AB  - The transmembrane domain of the nicotinic acetylcholine receptor (nAChR) is
      predominantly alpha-helical, and of the four distinctly different transmembrane M
      segments, only the helicity of M1 is ambiguous. In this study, we have
      investigated the conformation of a membrane-embedded synthetic M1 segment by
      solid-state nuclear magnetic resonance (NMR) methods. A 35-residue peptide
      representing the extended alphaM1 domain 206-240 of the Torpedo californica nAChR
      was synthesized with specific 13C - and 15N-labelled amino acids, and was
      incorporated in different phosphatidylcholine model membranes. The chemical shift
      of the isotopic labels was resolved by magic angle spinning (MAS) NMR and could
      be related to the secondary structure of the alphaM1 analog at the labelled
      sites. Our results show that the membrane-embedded alphaM1 segment forms an
      unstable alpha-helix, particularly near residue Leu18 (alphaLeu223 in the entire
      nAChR). This non-helical tendency was most pronounced when the peptide was
      incorporated in fully hydrated phospholipid bilayers, with an estimated 40-50% of
      the peptides having an extended conformation at position Leu18. We propose that
      the conserved proline residue at position 16 in the alphaM1 analog imparts a
      conformational flexibility on the M1 segments that could enable membrane-mediated
      modulation of nAChR activity.

PMID- 15471570
TI  - OVCAR-3 cells internalize TAT-peptide modified liposomes by endocytosis.
AB  - For cytosolic delivery of liposomes containing macromolecular drugs, such as
      proteins or nucleic acids, it would be beneficial to bypass endocytosis to
      prevent degradation in the lysosomes. Recent reports pointed to the possibility
      that coupling of TAT-peptides to the outer surface of liposome particles would
      enable translocation over the cellular plasma membrane. Here, we demonstrate that
      cellular uptake of TAT-liposomes occurs via endocytosis rather than plasma
      membrane translocation. The coupling of HIV-1 derived TAT-peptide to liposomes
      enhances their binding to ovarian carcinoma cells. The binding was inhibited by
      the presence of heparin or dextran sulfate, indicating that cell surface
      proteoglycans are involved in the binding interaction. Furthermore, living
      confocal microscopy studies revealed that binding of the TAT-liposomes to the
      plasma membrane is followed by intracellular uptake in vesicular structures.
      Staining the endosomes and lysosomes demonstrated that fluorescent liposomal
      labels are present within the endosomal and lysosomal compartments. Furthermore,
      incubation at low temperature or addition of a metabolic or an endocytosis
      inhibitor blocked cellular uptake. In conclusion, coupling TAT-peptide to the
      outer surface of liposomes leads to enhanced endocytosis of the liposomes by
      ovarian carcinoma cells, rather than direct cytosolic delivery by plasma membrane
      translocation.

PMID- 15471571
TI  - A dynamic phase microscopic study of optical characteristics of individual
      chloroplasts.
AB  - Dynamic phase microscopy (DPM) allows the monitoring of optical path difference
      (or phase height), h(x,y,t) approximately integraln(x,y,z,t)dz, an integral
      refractive index projection of the medium, n(x,y,z,t), in optically transparent
      biological specimens at high spatial and temporal resolutions. In this study, DPM
      was used for the analysis of fluctuations in the optical characteristics of
      individual bean chloroplasts in various metabolic states. A "phase image" of an
      individual chloroplast, which represents a three-dimensional plot of the "phase
      height", was obtained for the first time, and the frequency spectra of the
      fluctuations of h(x,y,t) were investigated. The fluctuation patterns, i.e., the
      intensity and the frequency spectra of phase height fluctuations in bean
      chloroplasts (Class B) were found to depend on their metabolic state. Under
      conditions of noncyclic (or pseudocyclic) electron transport, the fluctuations
      displayed characteristic frequencies in the range of 0.25-0.6 Hz and were space
      time-correlated in the chloroplast domains with the cross sizes of approximately
      2 microm. The fluctuation intensity decreased in the presence of uncouplers
      (nigericin and valinomycin, 20 microM). A stronger (in comparison with 20 microM
      valinomycin) effect of 20 microM nigericin suggests that the light-induced
      generation of the transmembrane pH difference (DeltapH) makes the main
      contribution to the increment of space-correlated fluctuations of h(x,y,t).
      Studies of chloroplasts incubated in media of various osmolarity (50-500 mM
      sucrose) have shown that structural changes in thylakoids are among other factors
      responsible for phase height fluctuations.

PMID- 15471572
TI  - Reduced kinetic models of facilitative transport.
AB  - In spite of the highly complex structural dynamics of globular proteins, the
      processes mediated by them can usually be described in terms of relatively simple
      kinetic diagrams. How do complex proteins, characterized by undergoing
      transitions among a possibly very large number of intermediate states, exhibit
      functional properties that can be interpreted in terms of kinetic diagrams
      consisting of only a small number of states? One possible way of explaining this
      apparent contradiction is that, under some conditions, a reduction of the actual
      complete kinetic diagram that describes all of the macromolecular states and
      transitions takes place. In this work, we contribute with a formal basis to this
      interpretation, by generalizing the procedure of diagram reduction to the case of
      multicyclic kinetic diagrams. As an example, we apply the procedure to a complex
      kinetic model of facilitative transport. We develop Monte Carlo simulations to
      obtain the kinetic parameters of the complex model and we compare them with the
      ones analytically obtained from the reduced model. We confirm that, under some
      conditions, the kinetic behavior of the complex transporter is indistinguishable
      from the one of a four-state simple carrier model, derived from the former by
      diagram reduction. Besides introducing some novel methodological aspects, this
      work further contributes to the idea that, under many physiological and
      experimental conditions, a reduction occurs of the complete kinetic diagram that
      describes the dynamics of a globular protein.

PMID- 15471573
TI  - The interaction of ethanol with reconstituted synaptosomal plasma membrane Ca2+ 
      ATPase.
AB  - The primary effect of ethanol is on the central nervous system. However, the
      molecular mechanisms responsible for the physiological symptoms of ethanol
      intoxication are still unknown. Low concentrations of ethanol were observed to
      stimulate the activity of the calcium pump from reconstituted synaptosomal plasma
      membrane Ca2+ -ATPase (PMCA), and ethanol inhibited Ca2+ -ATPase activity at
      concentrations above 5%. The greatest stimulating effect was obtained with 5%
      (v/v) ethanol and was lipid-dependent, being 74% when the protein had been
      reconstituted in phosphatidylcholine (PC) and less when the reconstituted protein
      had previously been activated by calmodulin or after removal of a 9-kDa
      autoinhibitory site by controlled trypsinization. Stimulation of the pump by
      ethanol was lower for the native or trypsin-digested protein in the presence of
      phosphatidylserine than in PC. These results suggest a direct ethanol-protein
      interaction, because the activating effect depended on the state of Ca2+ -ATPase
      (native or truncated, or in presence of calmodulin). The activating mechanism of
      ethanol may involve opening an autoinhibitory domain located close to the
      calmodulin binding domain.

PMID- 15471574
TI  - Prolactin directly stimulated the solvent drag-induced calcium transport in the
      duodenum of female rats.
AB  - Prolactin has been reported to stimulate the calcium absorption of the duodenum
      where three components of the active calcium transport, namely transcellular
      active, voltage-dependent and solvent drag-induced calcium transport, were
      identified. It was known that the transcellular active, but not the voltage
      dependent, duodenal calcium transport was directly stimulated by prolactin. The
      present study thus aimed to evaluate the direct action of prolactin on the
      solvent drag-induced duodenal calcium transport by using the Ussing chamber
      technique. The jejunum was used as a reference for the existence of solvent drag
      and the widening of tight junction induced by cytochalasin E. Results showed that
      the solvent drag-induced calcium transport existed in both intestinal segments,
      but the magnitude was significantly greater in the duodenum (29.27+/-2.27 vs.
      17.31+/-1.65 nmol h(-1) cm(-2), P<0.001). We further demonstrated that 200, 600
      and 800, but not 1000 ng/ml, prolactin significantly promoted the solvent drag
      induced duodenal calcium transport in a dose-response manner, i.e. from the
      control value of (nmol h(-1) cm(-2)) 24.31+/-2.36 to 45.42+/-3.47 (P<0.01),
      63.82+/-5.28 (P<0.001) and 53.93+/-5.41 (P<0.01), respectively. However,
      prolactin did not manifest any effect on the jejunum. Because the paracellular
      transport was suggested to be size-selective as well as charge-selective, further
      experiments were designed to evaluate the mechanism by which prolactin stimulated
      the solvent drag-induced calcium transport. The duodenum was exposed to 20 microM
      cytochalasin E, 600 ng/ml prolactin or the combination of both in the presence of
      a paracellular marker 3H-mannitol, while the jejunum was a positive reference.
      The results showed that, in the jejunum, cytochalasin E alone and cytochalasin E
      plus prolactin significantly increased the mannitol fluxes from (micromol h(-1)
      cm(-2)) 0.29+/-0.04 to 0.49+/-0.03 (P<0.05) and 0.48+/-0.05 (P<0.05),
      respectively, while having no effect on the calcium fluxes. Prolactin alone had
      no effect on the jejunal calcium flux. In the duodenum, neither mannitol nor
      calcium fluxes were enhanced by cytochalasin E, however, prolactin still
      increased the solvent drag-induced calcium flux from 27.74+/-2.41 to 51.03+/-4.35
      nmol h(-1) cm(-2) (P<0.001). It was concluded that prolactin directly stimulated
      the solvent drag-induced duodenal calcium transport in a dose-response and
      biphasic manner without the widening of tight junction.

PMID- 15471575
TI  - Effect of electric field vectoriality on electrically mediated gene delivery in
      mammalian cells.
AB  - Electropermeabilization is a nonviral method used to transfer genes into living
      cells. Up to now, the mechanism is still to be elucidated. Since cell
      permeabilization, a prerequired for gene transfection, is triggerred by electric
      field, its characteristics should depend on its vectorial properties. The present
      investigation addresses the effect of pulse polarity and orientation on membrane
      permeabilization and gene delivery by electric pulses applied to cultured
      mammalian cells. This has been directly observed at the single-cell level by
      using digitized fluorescence microscopy. While cell permeabilization is only
      slightly affected by reversing the polarity of the electric pulses or by changing
      the orientation of pulses, transfection level increases are observed. These last
      effects are due to an increase in the cell membrane area where DNA interacts.
      Fluorescently labelled plasmids only interact with the electropermeabilized side
      of the cell facing the cathode. The plasmid interaction with the
      electropermeabilized cell surface is stable and is not affected by pulses of
      reversed polarities. Under such conditions, DNA interacts with the two sites of
      the cell facing the two electrodes. When changing both the pulse polarity and
      their direction, DNA interacts with the whole membrane cell surface. This is
      associated with a huge increase in gene expression. This present study
      demonstrates the relationship between the DNA/membrane surface interaction and
      the gene transfer efficiency, and it allows to define the experimental conditions
      to optimize the yield of transfection of mammalian cells.

PMID- 15471576
TI  - Modulation of renal CNG-A3 sodium channel in rats subjected to low- and high
      sodium diets.
AB  - In this work, we studied the mRNA distribution of CNG-A3, an amiloride-sensitive
      sodium channel that belongs to the cyclic nucleotide-gated (CNG) family of
      channels, along the rat nephron. The possible involvement of aldosterone in this
      process was also studied. We also evaluated its expression in rats subjected to
      diets with different concentrations of sodium or to alterations in aldosterone
      plasma levels. Total RNA isolated from whole kidney and/or dissected nephron
      segments of Wistar rats subjected to low- and high-sodium diets, furosemide
      treatment, adrenalectomy, and adrenalectomy with replacement by aldosterone were
      analyzed by the use of Western blot, ribonuclease protection assay (RPA) and/or
      reverse transcription followed by semi-quantitative polymerase chain reaction (RT
      PCR). CNG-A3 sodium channel mRNA and protein expression, in whole kidneys of rats
      subjected to high-Na+ diet, were lower than those in animals given a low-salt
      diet. Renal CNG-A3 mRNA expression was also decreased in adrenalectomized rats,
      and was normalized by aldosterone replacement. Moreover, a CNG-A3 mRNA expression
      study in different nephron segments revealed that aldosterone modulation is
      present in the cortical thick ascending loop (cTAL) and cortical collecting duct
      (CCD). This result suggests that CNG-A3 is responsive to the same hormone
      signaling as the amiloride sensitive sodium channel ENaC and suggests the CNG-A3
      may have a physiological role in sodium reabsorption.

PMID- 15471577
TI  - Impact of the growth phase on the activity of multidrug resistance pumps and
      membrane potential of S. cerevisiae: effect of pump overproduction and carbon
      source.
AB  - The potentiometric fluorescence probe diS-C3(3) is expelled from S. cerevisiae by
      ABC pumps Pdr5 and Snq2 and can conveniently be used for studying their
      performance. The activity of these pumps in a strain with wild-type PDR1 allele
      was shown to drop sharply on glucose depletion from the medium and then again at
      the end of the diauxic shift when the cells are adapted to growth on respiratory
      substrates. The presence of the PDR1-3 allele causing pump overproduction
      prevented this second drop and the pump activity typical for diauxic cells was
      largely retained. Growth phase-dependent changes of membrane potential measured
      by the same probe in pump-free mutants included a Deltapsi drop in the late
      exponential and diauxic growth phase, indicating lowered activity of H+ -ATPase.
      Suppression of activity of both ABC pumps and H+ -ATPase obviously signifies cell
      transition to an energy-saving mode. Challenging respiration-adapted cells with
      glucose showed a novel feature of yeast ABC pumps--a strong dependence of pump
      activity on the type of the carbon source.

PMID- 15471578
TI  - KLN-5: a safe monocationic lipophosphoramide to transfect efficiently
      haematopoietic cell lines and human CD34+ cells.
AB  - The safe and efficient delivery of nucleic acids into haematopoietic stem cells
      (HSCs) has a wide range of therapeutic applications. Although viruses are being
      used in most clinical trials owing to their high transfection efficacy, recent
      results highlight many concerns about their use. Synthetic transfection reagents,
      in contrast, have the advantage of being safe and easy to manage while their low
      transfection efficiency remains a hurdle that needs to be addressed before they
      can be widely used. Using information on transfection mechanisms, a new family of
      monocationic lipids called lipophosphoramides was synthesized. Their efficiency
      to transfer genes into haematopoietic cell lines (K562, Jurkat and Daudi) and
      CD34+ cells was assessed. In this study, we report that one of these new
      compounds, KLN-5, leads to more efficient transfection activity than one of our
      previously most efficient reagents (EG-308) and the commercially available
      monocationic lipids (DC-CHOL and DOTAP/DOPE) (P<0.05). In addition, only a slight
      toxicity related to the chemical structure of the new compounds is observed.
      Moreover, we show that KLN-5 can successfully carry the transgene into
      haematopoietic progenitor cells (CD34+). These results demonstrate that synthetic
      transfection reagents represent a viable alternative to viruses and could have
      potential practical utility in a number of applications.

PMID- 15471579
TI  - Acoustically active liposomes for drug encapsulation and ultrasound-triggered
      release.
AB  - Acoustically active liposomes (AAL), previously developed as ultrasound contrast
      agents, contain small amounts of air. These AAL have potential to carry
      pharmaceutics and their acoustic activity could enable them to respond to
      ultrasound stimulation by releasing their contents. Since liposomes can entrap
      many kinds of drugs, if such entrapment did not affect their echogenicity, then
      the release of contents could potentially be controlled by ultrasound
      stimulation. The aim of this research was to investigate the capacity of
      acoustically active liposomes for hydrophilic molecule encapsulation and to
      determine their sensitivity to ultrasound-triggered release. Liposomes, composed
      of phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, and
      cholesterol, were made acoustically active by hydrating a lipid film, sonication,
      freezing in the presence of mannitol, lyophilization, and rehydration. As a test
      molecule, calcein was added in the hydration step. The procedure for generating
      acoustically active liposomes was compatible with an encapsulation efficiency of
      15% or more. The presence of mannitol during freeze-drying was essential not only
      for generation of acoustic activity but also for efficient encapsulation.
      Ultrasound-triggered release was achieved by applying 1 MHz ultrasound at 2 W/cm2
      for 10 s. The inclusion of 4% diheptanolyphosphatidylcholine (DHPC) increased the
      sensitivity of liposomes to ultrasound stimulation and resulted in very efficient
      stimulated release of contents (1/3 released in 10 s, 2/3 released in six such
      applications). Release of contents was highly correlated with the loss of air
      induced either by ultrasound or rapid pressure reduction. These encapsulation and
      triggered release techniques are highly efficient, and hence may be applicable to
      drug delivery.

PMID- 15471580
TI  - Vesicle size-dependent translocation of penetratin analogs across lipid
      membranes.
AB  - The recent discoveries of serious artifacts associated with the use of cell
      fixation in studies of the cellular uptake of cell-penetrating peptides (CPPs)
      have prompted a reevaluation of the current understanding of peptide-mediated
      cellular delivery. Following a report on the differential cellular uptake of a
      number of penetratin analogs in unfixed cells, we here investigate their membrane
      translocation abilities in large and giant unilamellar vesicles (LUVs and GUVs,
      respectively). Surprisingly, in contrast to the behavior in living cells, all
      peptides readily entered the giant vesicles (>1 microm) as proved by confocal
      microscopy, while none of them could cross the membranes of LUVs (100 nm). For
      determination of the location of the peptides in the LUVs, a new concept was
      introduced, based on sensitive resonance energy transfer (RET) measurements of
      the enhanced fluorescence of acceptor fluorophores present solely in the inner
      leaflet. An easily adopted method to prepare such asymmetrically labeled
      liposomes is described. The membrane insertion depths of the tryptophan moieties
      of the peptides were determined by use of brominated lipids and found to be very
      similar for all of the peptides studied. We also demonstrate that infrared
      spectroscopy on the lipid carbonyl stretch vibration peak is a convenient
      technique to determine phospholipid concentration.

PMID- 15471581
TI  - The effect of bacteriorhodopsin, detergent and hydration on the cubic-to-lamellar
      phase transition in the monoolein-distearoyl phosphatidyl glycerol-water system.
AB  - The cubic phase of monoolein (MO) has successfully been used for crystallization
      of membrane proteins. It is likely that the transition to a lamellar phase upon
      dehydration is important for the crystallization process, and that the internal
      dimensions of the lipid phases (i.e., water pore diameter) are crucial for the
      inclusion and the diffusion of membrane proteins. In the present study, we
      investigated the cubic-to-lamellar phase transitions in the MO-water and the MO
      distearoyl phosphatidyl glycerol (DSPG) systems. The MO-water system was
      investigated by means of isothermal sorption and desorption microcalorimetry. We
      show that the transition from cubic to lamellar phase induced by desorption is
      driven by entropy. At 25 degrees C, this occurs at a water activity of 0.98 with
      a transition enthalpy of 860 J/mol (MO). The phase behavior was also investigated
      in the presence of a small amount of the transmembrane protein bacteriorhodopsin
      (bR), and a detergent, octyl glucoside (OG), and it was shown that both bR and OG
      stabilize the lamellar phase. Analogous results were obtained for the MO-DSPG
      water system. The latter system resembles the MO-water system in that a cubic-to
      lamellar phase transition is induced by dehydration, although the structural
      properties of these phases are slightly different. Finally, we demonstrate that
      bR can be crystallized from a cubic phase of MO-DSPG-buffer.

PMID- 15471582
TI  - The elution profile of immobilized liposome chromatography: determination of
      association and dissociation rate constants.
AB  - The interaction of lipophilic cations, tetraphenylphosphonium and
      triphenylphosphonium homologues with liposomes was investigated using immobilized
      liposome chromatography (ILC). Large unilamellar liposomes with a mean diameter
      of 100 nm were stably immobilized in chromatographic gel beads by avidin-biotin.
      The distribution coefficient calculated from (Ve-V0)/Vs (Ve, retention volume;
      V0, the void volume; Vs, the stationary phase volume) was found to be independent
      of flow rate, injection amount and gel bed volume, which is consistent with
      chromatograph theory. The relationship between the bandwidth and solvent flow
      rate did not follow band-broadening theories reported thus far. We hypothesized
      that the solvent might be forced to produce large eddies, spirals or turbulent
      flow due to the presence of liposomes fixed in the gel. Therefore, we developed a
      new theory for ILC elution: The column is composed of a number of thin disks
      containing liposomes and solution, and within each disk the solution is well
      mixed. This theory accounts for our results, and we were able to use it to
      estimate the rate constants of association and dissociation of the phosphonium
      to/from liposomes.

PMID- 15471583
TI  - Spin-labelled vacuolar-ATPase inhibitors in lipid membranes.
AB  - Two spin-labelled derivatives of the 5-(2-indolyl)-2,4-pentadienoyl class of
      inhibitors of the vacuolar ATPase have been synthesised and their EPR properties
      characterised in phospholipid membranes. One spin-labelled inhibitor is the amide
      derivative of pentadienic acid and 4-amino-TEMPO (INDOL6), and the other is the 3
      hydroxymethyl-PROXYL ester (INDOL5). The response of the EPR spectra to the chain
      melting transition of dimyristoyl phosphatidylcholine (DMPC) bilayers
      demonstrates that both derivatives incorporate in phospholipid membranes. The
      axially anisotropic EPR spectra of INDOL6 in fluid DMPC membranes indicate that
      the indolyl-pentadienoyl inhibitors intercalate between the lipid chains, in the
      membrane. INDOL5, designed to possess additional internal segmental mobility,
      exhibits more nearly isotropic motion of the spin-label moiety in fluid membranes
      than does INDOL6. The EPR characteristics of INDOL5 are therefore well suited to
      detecting specific ligand-protein interactions. Progressive saturation EPR
      experiments with polar and hydrophobic relaxation agents (aqueous Ni2+ and
      oxygen) show that the nitroxide group is buried in the membrane, with the indole
      moiety providing the anchor at the membrane polar-apolar interface. Rates of spin
      label reduction by externally added ascorbate confirm this assignment. These two
      spin-labelled derivatives provide complementary EPR probes of the lipid
      environment (INDOL6), and of ligand-protein interactions (INDOL5), for this class
      of V-ATPase inhibitor.

PMID- 15471584
TI  - Solid support membranes for ion channel arrays and sensors: application to rapid
      screening of pharmacological compounds.
AB  - The use of solid supported membranes (SSM) was investigated for reconstitution of
      ion channels and for potential application to screen pharmacological reagents
      affecting ion channel function. The voltage-gated Kv1.5 K+ channel was
      reconstituted on an SSM and a current was measured. This current was dependent on
      the presence of K+, but not Na+, indicating that the Kv1.5 K+ channel maintained
      cation specificity when reconstituted on SSM. Two pharmacological reagents
      applied to Kv1.5 K+ channels reconstituted on SSM had similar inhibitory effects
      as those measured using Kv1.5 in biological membranes. SSM-mounted ion channels
      were stable enough to be washed with buffer solution and reused many times,
      allowing solution exchange essential for pharmacological drug screening.

PMID- 15471585
TI  - Endovesicle formation and membrane perturbation induced by
      polyoxyethyleneglycolalkylethers in human erythrocytes.
AB  - Polyoxyethyleneglycolalkylether (CmEn, m=12, n=8) can induce a large torocyte
      like endovesicle in human erythrocytes. The present study aimed to examine how
      variations in the molecular structure of CmEn (m=10,12,14,16,18; n=1-10,23)
      affect the occurrence of torocyte endovesicles. Our results show that torocytes
      occur most frequently when m=12,14 and n=8,9. At this molecular configuration the
      detergents induce inward membrane bending (stomatocytic S1-S2 shapes) resulting
      in the formation of a large membrane invagination. These detergents have a strong
      membrane perturbing, i.e., haemolytic, effect. Theoretical calculations indicate
      that a torocyte-shaped inside-out membrane vesicle can be created from a large
      membrane invagination due to the impact of laterally mobile anisotropic membrane
      inclusions. Such inclusions may be detergent-membrane component complexes or
      unanchored integral membrane proteins. It is shown that a nonhomogeneous lateral
      distribution of anisotropic membrane inclusions may stabilise the torocyte
      endovesicle shape, characterised by having opposite membranes in the thin central
      region of the vesicles separated by a certain distance. Tubular, conical or
      inverted conical isotropic inclusions cannot do so.

PMID- 15471587
TI  - Tonic excitation and inhibition of neurons: ambient transmitter sources and
      computational consequences.
AB  - Tonic activation of excitatory and inhibitory receptors, by the ambient
      concentration of neurotransmitters in the extracellular space of the brain, has
      been suggested to underlie phenomena as diverse as relapse to cocaine use by
      reward pathways in the striatum, sparse coding of motor information in the
      cerebellum, and control of the development of the cerebral and cerebellar
      cortices. Here we assess the mechanisms which may determine the ambient levels of
      excitatory and inhibitory neurotransmitters, and consider their likely effect on
      information processing.

PMID- 15471588
TI  - Simple models of stimulation of neurones in the brain by electric fields.
AB  - The excitation of pyramidal cells in the motor cortex, produced by electric
      fields generated by distant electrodes or by electromagnetic induction, has been
      modelled. Linear, steady-state models of myelinated axons capture most of the
      geometrical aspects of neurone activation in electric fields. Some non-linear
      features can be approximated. Models with a proximal sealed-end and distal
      infinite axon, or of finite length, are both serviceable. Surface anodal
      stimulation produces hyperpolarisation of the proximal axon (closest to the
      anode) and depolarisation in the distal axon. The point of maximum depolarisation
      can be influenced by the location of the cathode (greater separation of anode and
      cathode causes more distal depolarisation). Axon bends can produce very localised
      depolarisation. Cathodal stimulation may be less effective than anodal as a
      result of anodal block of conduction of action potentials in the distal axon. The
      latencies of responses to anodal stimulation, recorded in the distal axon, will
      decrease as the stimulus strength is increased and the point of action potential
      initiation moves distally node by node. Larger jumps in latency will be produced
      when the point of action potential initiation moves from one axon bend to
      another.

PMID- 15471589
TI  - Presynaptic, extrasynaptic and axonal GABAA receptors in the CNS: where and why?
AB  - Although GABA(A) receptors are widely distributed at inhibitory synapses on
      dendrites and cell bodies of neurons, they also occur in other places, in
      particular at synapses made on axons and in extrasynaptic membranes. This review
      summarises some of the evidence that presynaptic receptors modulate transmission
      not only at primary afferents in the spinal cord, but also at a variety of sites
      in the brain, including hippocampal mossy fibres. These receptors modulate
      transmitter release via several different mechanisms. Another form of
      unconventional GABA(A) receptor-mediated signalling is the mediation of a tonic
      conductance, seen in granule cells of the cerebellum and dentate gyrus and also
      in hippocampal interneurons. Tonic signalling appears to be mediated by
      extrasynaptic receptors. The adaptive significance of this form of signalling
      remains poorly understood.

PMID- 15471590
TI  - Dimensionality in cardiac modelling.
AB  - The development of mathematical models of the heart has been an ongoing concern
      for many decades. The initial focus of this work was on single cell models that
      incorporate varyingly detailed descriptions of the mechanisms that give rise to
      experimentally observed action potential shapes. Clinically relevant heart rhythm
      disturbances, however, are multicellular phenomena, and there have been many
      initiatives to develop multidimensional representations of cardiac
      electromechanical activity. Here, we discuss the merits of dimensionality, from
      0D single cell models, to 1D cell strands, 2D planes and 3D volumes, for the
      simulation of normal and disturbed rhythmicity. We specifically look at models
      of: (i) the origin and spread of cardiac excitation from the sino-atrial node
      into atrial tissue, and (ii) stretch-activated channel effects on ventricular
      cell and tissue activity. Simulation of the spread of normal and disturbed
      cardiac excitation requires multicellular models. 1D architectures suffer from
      limitations in neighbouring tissue effects on individual cells, but they can
      (with some modification) be applied to the simulation of normal spread of
      excitation or, in ring-like structures, re-entry simulation (colliding wave
      fronts, tachycardia). 2D models overcome many of the limitations imposed by
      models of lower dimensionality, and can be applied to the study of complex co
      existing re-entry patterns or even fibrillation. 3D implementations are closest
      to reality, as they allow investigation of scroll waves. Our results suggest that
      2D models offer a good compromise between computational resources, complexity of
      electrophysiological models, and applicability to basic research, and that they
      should be considered as an important stepping-stone towards anatomically detailed
      simulations. This highlights the need to identify and use the most appropriate
      model for any given task. The notion of a single and ultimate model is as useful
      as the idea of a universal mechanical tool for all possible repairs and servicing
      requirements in daily life. The ideal model will be as simple as possible and as
      complex as necessary for the particular question raised.

PMID- 15471591
TI  - Mechanisms underlying gamma ('40 Hz') network oscillations in the hippocampus--a
      mini-review.
AB  - Gamma-frequency oscillations (approximately 30-100 Hz) in cortical network
      activity have been proposed to provide a temporal structure for various forms of
      cognitive processing. This review provides an update on recent experiments
      addressing the mechanisms underlying gamma-frequency network oscillations in the
      rodent hippocampus. Particular emphasis is placed on the correlation between in
      vivo observations and in vitro models.

PMID- 15471593
TI  - Does inhibition balance excitation in neocortex?
AB  - The distribution of inhibitory and excitatory synapses on neocortical neurons is
      at odds with a simple view that cortical functioning can persist by maintaining a
      balance between inhibitory and excitatory drives. Pyramidal cells can potentially
      be shut down by very powerful proximal inhibitory synapses, despite these
      accounting for perhaps less than 1% of their total number of synaptic inputs.
      Interneurons in contrast are dominated by excitatory inputs. These may be
      powerful enough to effect an apparent depolarizing block at the soma. In this
      extreme case though, models suggest that action potentials are generated down the
      axon, and the cells behave like integrate-and-fire neurons. We discuss possible
      network implications of these modelling studies.

PMID- 15471592
TI  - Early computational processing in binocular vision and depth perception.
AB  - Stereoscopic depth perception is a fascinating ability in its own right and also
      a useful model of perception. In recent years, considerable progress has been
      made in understanding the early cortical circuitry underlying this ability.
      Inputs from left and right eyes are first combined in primary visual cortex (V1),
      where many cells are tuned for binocular disparity. Although the observation of
      disparity tuning in V1, combined with psychophysical evidence that stereopsis
      must occur early in visual processing, led to initial suggestions that V1 was the
      neural correlate of stereoscopic depth perception, more recent work indicates
      that this must occur in higher visual areas. The firing of cells in V1 appears to
      depend relatively simply on the visual stimuli within local receptive fields in
      each retina, whereas the perception of depth reflects global properties of the
      stimulus. However, V1 neurons appear to be specialized in a number of respects to
      encode ecologically relevant binocular disparities. This suggests that they carry
      out essential pre-processing underlying stereoscopic depth perception in higher
      areas. This article reviews recent progress in developing accurate models of the
      computations carried out by these neurons. We seem close to achieving a
      mathematical description of the initial stages of the brain's stereo algorithm.
      This is important in itself--for instance, it may enable improved stereopsis in
      computer vision--and paves the way for a full understanding of how depth
      perception arises.

PMID- 15471594
TI  - Backpropagating action potentials in neurones: measurement, mechanisms and
      potential functions.
AB  - Here we review some properties and functions of backpropagating action potentials
      in the dendrites of mammalian CNS neurones. We focus on three main aspects:
      firstly the current techniques available for measuring backpropagating action
      potentials, secondly the morphological parameters and voltage gated ion channels
      that determine action potential backpropagation and thirdly the potential
      functions of backpropagating action potentials in real neuronal networks.

PMID- 15471595
TI  - [Hospital physicians: the roots of unrest].

PMID- 15471596
TI  - [Prescribing patterns of rofecoxib in the primary care setting: results of a
      French survey].
AB  - OBJECTIVES: To assess the prescribing patterns of rofecoxib, a selective cyclo
      oxygenase-2 inhibitor or coxib relative to those of conventional non steroidal
      anti-inflammatory drugs (NSAIDs) in the primary care setting in France. METHODS:
      A representative sample of 1010 French general practitioners participated in the
      study. They recorded the demographic, medical and pharmaceutical characteristics
      of all patients for whom they prescribed an NSAID between July 1, 2001 and June
      30, 2002. RESULTS: The prescribing patterns of rofecoxib were similar for both
      available dosages (12.5 and 25 mg). The proportion of patients aged 65 years and
      older was significantly higher among those receiving rofecoxib (48%) than among
      those receiving a traditional NSAID (37.3%). A history of peptic ulcer or
      gastrointestinal bleeding was more frequent in the former (4.8%) than in the
      latter (2.1%). Low dose aspirin and antihypertensive agents were being taken in
      6.1% and 34.8%, respectively, of the patients in the rofecoxib group versus 2.3%
      and 15.6%, respectively, in the conventional NSAID group. Concurrent use of a
      proton pump inhibitor (PPI) was marginally less frequent in the rofecoxib group
      (16.9%) than in the conventional NSAID group (18.6%). However, a significantly
      higher proportion of patients were given a PPI prior to rofecoxib therapy (10.4%)
      than prior to conventional NSAID therapy (3.7%). CONCLUSION: Our findings show
      that French general practitioners are more likely to prescribe rofecoxib for
      patients who have risk factors of NSAID gastropathy.

PMID- 15471597
TI  - [Resurgence of syphilis: a prospective study at an University Hospital, Nimes].
AB  - BACKGROUND: Since 2000, the incidence of syphilis has increased in France. The
      study objective was to estimate the frequency of syphilis in Languedoc Roussillon
      region in Southern France. METHOD: The prospective study was conducted between
      January 1, 2003 and June 30, 2003 in different medical wards in a French
      University Hospital, Nimes. The diseased patients in this study answered to a
      questionnaire, providing epidemiological and socio-economic data, symptomatology
      and treatment-seeking behaviour. Blood specimens were tested for syphilis by the
      serological methods (TPHA, VDRL, FTA). RESULTS: In 6 months, serologic evidence
      of syphilis infection was found in 30 patients. Men were more than twice as
      likely as women to be infected with syphilis. Most men (64.7%) acquired the
      infection homosexually. Four women acquired infection during pregnancy. The mean
      age of study population was 46.3 years. 40.7% were married. Out of 27 cases,
      70.4% cases had an associated sexually transmitted infection (HIV, hepatitis,
      herpes, and gonorrhoea). CONCLUSIONS: These data confirm the increase of syphilis
      in south of France and underline the importance of a permanent monitoring of
      sexually transmitted infection in target populations to allow a timely diagnosis
      and an appropriate treatment, and to plan preventive strategies.

PMID- 15471598
TI  - [Treatments for pulmonary arterial hypertension].
AB  - PURPOSE: Pulmonary arterial hypertension (PAH) is characterized by
      vasoconstriction, in situ thrombosis and vascular remodeling of small pulmonary
      arteries inducing a fixed pulmonary arterial obstruction and persistent elevation
      of pulmonary arterial resistance. Conventional treatment is based on simple
      measures (exercise limitation) and non-specific drugs (warfarine, diuretics,
      oxygen). CURRENT KNOWLEDGE AND KEY POINTS: Pure vasodilators like calcium channel
      antagonists have little or no effect on the vast majority of patients, presumably
      because fixed pulmonary arteriopathy predominate over vasoconstriction.
      Intravenous prostacyclin (epoprostenol) and endothelin receptor antagonists have
      vasodilator and antiproliferative properties. Epoprostenol therapy has resulted
      in significant improvements in prognosis of this disease and this drug remains
      the first-line treatment of the most severe patients. Bosentan is an interesting
      first-line treatment for NYHA functional class III patients. Availability of
      novel specific drugs (endothelin receptor type A antagonists, prostacyclin
      analogues, type 5 phosphodiesterase inhibitors) open new perspectives in
      treatment of PAH. The long-term benefit of these drugs remains to be evaluated
      and their respective place in treatment of these patients is still uncertain. We
      here present the different therapeutic alternatives available in the PAH and
      propose an algorithm for treatment of these patients. FUTURE PROSPECTS AND
      PROJECTS: The evolution of therapy from vasodilators to antiproliferative agents
      reflects the advancement in our understanding of the mechanisms mediating
      pulmonary arterial hypertension.

PMID- 15471599
TI  - [What place for DNA microarray in inflammatory diseases?].
AB  - PURPOSE: DNA chip is a recently developed technique allowing analysis of
      thousands of genes at the same time in multiple biological samples. In few years
      it has become an obligatory step in massive gene expression study. The enormous
      quantity of results generated and the new way of thinking allowed make this kind
      of study a true revolution. KEY MESSAGE AND RECENT FACTS: The enormous discovery
      potential permitted by the accomplishment of multiple genomes sequencing and the
      advent of technologies allowing massive gene expression analyses have totally
      modified the diseases approach. Considering the obtainment of a real full picture
      of the transcriptional activity in an organ, tissue or cell is now legitimate.
      DNA microarray is obviously not the only technique allowing such type of analysis
      but it is without contest the technology which is the most popular and the one
      which has been recently the subject of the most important developments. It is
      certainly the technology which brought the main advances in tumour classification
      and discovery of new biomarkers. The first results based on this technology in
      inflammatory diseases have recently been reported. PERSPECTIVE AND PROJECTS: The
      optimal use of DNA microarrays will necessitate a powerful statistical analysis
      and an high quality biological experimentation. Strict standard and quality
      criteria are developing. Obviously, the DNA chips have a role to play in
      multifactorial inflammatory diseases mainly through their potential to bring new
      answers to diagnostic and pathophysiological problems. One potential development
      of the technique in such diseases will be the definition of disease specific gene
      profiles and the generation of chips allowing the detection of few targeted genes
      with all the known mutations of these genes. The correlation of global or
      targeted gene expression with clinical and pathological data will allow a new
      step forward in the understanding and taking care of inflammatory diseases.

PMID- 15471600
TI  - [Systemic manifestations of Parvovirus B19 infections].
AB  - PURPOSE: Parvovirus B19 (B19) causes many clinical disorders, of which the most
      common are erythema infectiosum, aplastic crisis complicating chronic hemolytic
      anemia, and hydrops fetalis. In young adults, the skin eruption caused by B19 is
      accompanied by polyarthritis and polyarthralgia in 60% of the cases. Rheumatoid
      factors and other antibodies including antinuclear antibodies, anti-ADN, and
      antiphospholipids can be produced in the wake of B19 infection. CURRENT KNOWLEDGE
      AND KEY POINTS: These features may simulate systemic diseases as rheumatoid
      arthritis (RA), systemic lupus erythematosus (SLE) (lupus-like eruption over the
      cheeks, cytopenia, etc.) or vasculitis (purpura, renal involvement). In addition,
      there have been a few reports of SLE, vasculitis and other connective tissue
      diseases developing shortly after a B19 infection associated with virus clearance
      suggesting that B19 can act as a trigger of systemic disease. However, studies in
      large series indicate that in fact B19 is probably an extremely rare cause of RA,
      SLE or vasculitis. FUTURE PROSPECTS AND PROJECTS: In fundamental studies B19
      interacts with inflammatory cells by regulation of cytokines. More recently, two
      studies suggest that viral infection due to B19 may affect the course of SLE,
      leading to specific biological subsets. These preliminary findings require
      confirmation to elucidate the significance of the presence of B19 in systemic
      disease.

PMID- 15471601
TI  - [Rituximab and autoimmune disorders therapy].
AB  - INTRODUCTION: B lymphocytes play a central role in pathogenesis of autoimmune
      disease. This suggests that therapies directed against B lymphocytes may be
      effective for the treatment of human autoimmune mediated disease. EXEGESIS:
      Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen
      expressed on most B cells and is used to treat B cell non Hodgkin lymphoma.
      Rituximab is highly effective in depleting B lymphocytes in vivo. Such treatment
      could presumably eliminate B cells producing autoantibodies. Main mechanisms of
      action of Rituximab are discussed with implication in the management of
      autoimmune diseases. CONCLUSION: Use of Rituximab for autoimmune disorders
      therapy is attractive because of its effect on B lymphocytes. However,
      therapeutics indications have to be adapted to the inherent differences in the
      pathogenesis of autoimmune diseases to assess efficiency.

PMID- 15471602
TI  - [Bilateral optic neuropathy revealing systemic sarcoidosis].
AB  - INTRODUCTION: Although ocular involvement concerns about 25 to 60% of patients
      with systemic sarcoidosis, papilledema is a rare event. EXEGESIS: A 43-year-old
      man presented with left visual loss related to papillitis. Despite high-dose
      corticosteroids, visual loss became rapidly bilateral. Thoracic CT-scan showed
      mediastinal and parenchymal involvement. Histological study of lung, bronchial
      and lymphadenopathy biopsies displayed giant-cells granuloma without necrosis.
      Diagnosis of sarcoidosis complicated with optic neuropathy was made. Therapy
      combining prednisone, methotrexate and infliximab was started without significant
      improvement of visual acuity. CONCLUSION: This report underlines the potential
      severity of optic neuropathy in sarcoidosis.

PMID- 15471603
TI  - [Association of hereditary hemochromatosis and pernicious anaemia].
AB  - INTRODUCTION: Hereditary hemochromatosis is inherited as an autosomal recessive
      trait. It is characterized by increased absorption of dietary iron. The
      association between pernicious anaemia and hereditary hemochromatosis has never
      been described. EXEGESIS: We report a case of paradoxical association of
      hereditary hemochromatosis and pernicious anaemia. CONCLUSION: It seems that
      pernicious anaemia may prevent manifestations of hemochromatosis. We suppose that
      this protective role is due to atrophic body gastritis with iron malabsorption.

PMID- 15471604
TI  - [Pulmonary aneurysm in Behcet's disease].

PMID- 15471605
TI  - [Distal renal tubular acidosis ten years before Sjogren's syndrome].

PMID- 15471606
TI  - [Amyotrophic lateral sclerosis during multiple myeloma].

PMID- 15471607
TI  - [Tumor lysis syndrome after chemotherapy for colon small cell carcinoma].

PMID- 15471608
TI  - [Autoimmune hemolytic anemia caused by IgG cold agglutinins after infectous
      mononucleosis].

PMID- 15471609
TI  - [Genital ulcerations revealing an acute myelomonocytic leukaemia].

PMID- 15471610
TI  - Initial urinary epinephrine and cortisol levels predict acute PTSD symptoms in
      child trauma victims.
AB  - BACKGROUND: Previous research examining biological correlates of posttraumatic
      stress disorder (PTSD) in children has suggested that children with chronic PTSD
      have altered levels of catecholamines and cortisol compared to similarly
      traumatized children who do not meet diagnostic criteria. The present study
      extended these findings by examining whether urinary hormone levels collected
      soon after a trauma were related to subsequent acute PTSD symptoms in child
      trauma victims. METHODS: Initial 12-h urine samples were collected from 82
      children aged 8-18 admitted to a Level 1 trauma center. Collection was begun
      immediately upon admission, and samples were assayed for levels of catecholamines
      and cortisol. PTSD and depressive symptomatology were assessed 6 weeks following
      the accident. RESULTS: Initial urinary cortisol levels were significantly
      correlated with subsequent acute PTSD symptoms (r=0.31). After removing the
      variance associated with demographic variables and depressive symptoms, urinary
      cortisol and epinephrine levels continued to predict a significant percentage (7
      10%) of the variance in 6-week PTSD symptoms. Examination of boys and girls
      separately suggested that significance was primarily driven by the strength of
      the relationships between hormone levels and acute PTSD symptoms in boys.
      CONCLUSIONS: The present findings suggest that high initial urinary cortisol and
      epinephrine levels immediately following a traumatic event may be associated with
      increased risk for the development of subsequent acute PTSD symptoms, especially
      in boys.

PMID- 15471611
TI  - Increased cortisol and decreased right ear advantage (REA) in dichotic listening
      following a negative mood induction.
AB  - This study aimed to evaluate neuroendocrine responses and changes in perceptual
      asymmetry following an induced negative affect. Cortisol increasing in response
      to negative affect has been reported, while current brain models of emotion
      processing link negative affect to the right hemisphere. In this study, the
      Velten Mood Induction Procedure was used to generate neutral or negative affect
      in 44 healthy subjects. The PANAS scales were used to assess self-reported mood.
      A consonant-vowel dichotic listening (DL) test was applied after the neutral and
      negative affect inductions, and levels of salivary cortisol were determined by
      radioimmunoassay. For the negative affect condition, and congruent with the
      hypothesis tested, PANAS positive scores diminished (p<0.001) and PANAS negative
      scores increased (p<0.001), yielding an inverse correlation between them. A
      significant increase in cortisol levels was also seen (p<0.04). When taking
      cortisol reactivity into account, PANAS negative scores were higher for high-than
      for low-cortisol responders (p<0.02). Regarding DL, an increase in left ear items
      (p<0.04) and a decrease in right ear items (p<0.03) reported for those subjects
      who obtained a right ear advantage in the neutral condition. An explanation in
      terms of Kinsbourne's model for attentional-activation influences on DL is
      postulated and implications for the issue of affective illness are also
      discussed.

PMID- 15471612
TI  - The impact of time of waking and concurrent subjective stress on the cortisol
      response to awakening.
AB  - Both time of awakening and stress are thought to influence the magnitude of the
      cortisol awakening response (CAR), but the relative importance of these factors
      is unclear. This study assessed these influences in a combined within- and
      between-subject design. Data were collected from 32 men and women working as
      station staff in the London underground railway system in three conditions: early
      shift days, day-shift days, and control days. Saliva samples were obtained on
      waking, 30 and 60 min later, together with measures of concurrent subjective
      stress, sleep quality the night before, and accumulated stress at the end of the
      day. Participants woke up more than 3.5h earlier on average on early-shift than
      day-shift or control days, and cortisol levels on waking were lower in the early
      shift condition. The CAR (assessed both with increases from waking to 30 min and
      with area under the curve measures) was greater on early-shift days. However,
      respondents were more stressed over the hour after waking and reported more sleep
      disturbance on early-shift days; when these factors were taken into account, the
      difference in CAR related to experimental condition was no longer significant.
      Comparisons were also made between individuals who started their day-shifts in
      the morning and afternoon. The morning shift group woke an average of 2h earlier
      than did the afternoon shift group, but did not differ on stress, sleep quality,
      or CAR. Stress assessed retrospectively at the end of the day was not associated
      with the CAR. We conclude that early waking, stress early in the day, and sleep
      disturbance often coincide, but need to be distinguished in order accurately to
      interpret differences in CAR magnitude.

PMID- 15471613
TI  - Differential adaptation of neurocognitive brain functions to recurrent
      hypoglycemia in healthy men.
AB  - Antecedent hypoglycemia is known to attenuate hormonal and symptomatic responses
      to subsequent hypoglycemia. Whether this pertains also to hypoglycemia-induced
      cognitive dysfunction is controversially discussed. Neurocognitive adaptation
      might essentially depend on the type of function. Here, we compared the influence
      of recurrent hypoglycemia in 15 healthy men on counterregulatory hormones,
      subjective symptoms of hypoglycemia, short-term memory performance (word recall),
      and performance on an auditory attention task (oddball). The attention task was
      also used to record event-related brain potential (ERP) indicators of stimulus
      processing. In each subject, three consecutive hypoglycemic clamps were
      performed, two on day 1 and the third on day 2. Neurocognitive testing was
      performed during baseline and at two different hypoglycemic plateaus (2.8 and 2.5
      mmol/l) during the first and last clamp. As expected, hormonal responses were
      significantly reduced to the last as compared to the first hypoglycemia
      indicating adaptation. Subjective symptoms also decreased in response to
      recurrent hypoglycemia. Short-term memory performance deteriorated distinctly on
      the first hypoglycemic clamp, but maintained the normal level on the last clamp
      (P=0.006). Likewise, the impairment in reaction time (P=0.022) and response
      accuracy (P=0.005) was distinctly smaller on the last than first hypoglycemia. In
      parallel, the hypoglycemia-induced decrease in P3 amplitude (P=0.019) and the
      increase in P3 latency (P=0.049) were diminished with recurrent hypoglycemia,
      indicating that late stages of controlled stimulus processing likewise adapted.
      In contrast, the distinct decrease in amplitudes of the N1 and P2 components of
      the ERP (preceding the P3) was closely comparable in response to the first and
      last hypoglycemia (P>0.3). Together results indicate an adaptation to recurrent
      hypoglycemia for signs of controlled stimulus processing presumably involving
      hippocampo-prefrontocortical circuitry, while earlier automatic stages of
      processing appear to be spared.

PMID- 15471614
TI  - Child maltreatment and HPA axis dysregulation: relationship to major depressive
      disorder and post traumatic stress disorder in females.
AB  - A history of child maltreatment increases the vulnerability to the development of
      Major Depressive Disorder (MDD) and/or Posttraumatic Stress Disorder (PTSD),
      especially in females. Both MDD and PTSD are associated with a dysregulation of
      the Hypothalamic-Pituitary-Adrenal (HPA) axis. Dysregulation of the HPA axis may
      be an important etiological link between child maltreatment and subsequent
      psychiatric disorder, yet little is known about the relationship between exposure
      and outcome. The aim of this review is to explore the role of HPA axis
      dysregulation in the link between child maltreatment and MDD/PTSD among women.
      Studies of females with MDD frequently indicate a hyperactivity of the HPA axis,
      and contribute to our understanding of the underlying mechanisms involved in mood
      dysregulation. Evidence for HPA axis dysregulation in PTSD is less convincing and
      suggests that timing of the stressful experience as well as the type of the
      trauma may influence the outcome. The strongest evidence to date suggesting that
      the development of the HPA axis may be affected by early life stressful
      experiences comes from pre-clinical animal studies. Together these studies add to
      our understanding of the role of the HPA axis in psychiatric disorders in
      relation to stress. The literature on HPA axis function in both children and
      adults following child maltreatment further highlights the potential relevance of
      early stress to later onset of major psychiatric disorders. Such knowledge may
      also contribute to the development of early interventions targeted at primary
      prevention.

PMID- 15471615
TI  - Responsiveness of the hypothalamic-pituitary-adrenal axis to different novel
      environments is a consistent individual trait in adult male outbred rats.
AB  - Susceptibility to some stress-induced pathologies may be strongly related to
      individual differences in the responsiveness of the hypothalamic-pituitary
      adrenal (HPA) axis to stressors. However, there have been few attempts in rodents
      to study the reliability of the individual differences in the responsiveness of
      the HPA to stressors and the relationship to resting corticosterone levels. In
      the present work, we used a normal population of Sprague-Dawley rats, with a
      within-subject design. Our objectives were to study: (a) the reliability of the
      ACTH and corticosterone response to three different novel environments widely
      used in psychopharmacology and (b) the relationship between stress levels of HPA
      hormones and the daily pattern of corticosterone secretion (six samples over a 24
      h-period). Animals were repeatedly sampled using tail-nick procedure. The novel
      environments were the elevated plus-maze, the hole-board and the circular
      corridor. Animals were sampled just after 15 min exposure to the tests and again
      at 15 and 30 min after the termination of exposure to them (post-tests). The
      hormonal levels just after the tests indicate that the hole-board seems to be
      more stressful than the circular corridor and the elevated plus-maze, the latter
      being characterized by the lowest defecation rate. Correlational analysis
      revealed that daily pattern of resting plasma corticosterone levels did not
      correlate to HPA responsiveness to the tests, suggesting no relationship between
      resting and stress levels of HPA hormones. In contrast, the present study
      demonstrates, for the first time, a good within-subject reliability of the ACTH
      and corticosterone responses to the three environments, suggesting that HPA
      responsiveness to these kind of stressors is a consistent individual trait in
      adult rats, despite differences in the physical characteristics of the novel
      environments.

PMID- 15471616
TI  - Stress-induced changes in LPS-induced pro-inflammatory cytokine production in
      chronic fatigue syndrome.
AB  - OBJECTIVE: It has been suggested that a hypofunctional hypothalamic-pituitary
      adrenal (HPA) axis in chronic fatigue syndrome could result in an exaggerated
      release of pro-inflammatory cytokines during stress. As pro-inflammatory
      cytokines are involved in the induction of sickness behavior and thus constitute
      a potential physiological correlate of stress-induced symptom exacerbation in
      chronic fatigue syndrome, we set out to evaluate the LPS-induced production of
      pro-inflammatory cytokines during psychosocial stress in CFS and healthy
      controls. METHOD: Twenty-one CFS patients and 20 healthy controls matched for age
      and gender underwent a standardized psychosocial stress test (Trier social stress
      test, TSST). Adrenocorticotropine hormone (ACTH), salivary cortisol and plasma
      cortisol levels were measured before and repeatedly following exposure to the
      stressor. Lipopolysaccharide-stimulated production of interleukin-6 and tumor
      necrosis factor-alpha were assessed at baseline as well as 10 and 60 min after
      the stress test. RESULTS: CFS patients showed an inverse stress-induced response
      pattern of LPS-stimulated cytokines responses in comparison to healthy controls,
      i.e. stimulated cytokine production decreased shortly after stress in CFS
      patients, while it increased in controls. Fatigue scores and basal LPS-induced
      cytokine levels were significantly associated for TNF-alpha in controls and for
      both cytokines in CFS patients. Stress-induced changes in stimulated cytokine
      production were not associated with general fatigue scores in the control group,
      whereas in the CFS group, fatigue scores were significantly correlated with
      integrated levels of LPS-induced cytokines. However, partial correlations
      revealed that these results were due to the high correlations with basal LPS
      induced cytokine levels. CONCLUSION: CFS patients do not show an exaggerated
      secretion of LPS-induced cytokines. Although cortisol responses to stress were
      normal, pro-inflammatory cytokine levels in CFS patients were significantly
      attenuated. Possible intracellular mechanisms, such as for example an enhanced
      sensitivity to inhibitory effects of glucocorticoids, a diminished responsivity
      to catecholaminergic stimulation, and a disruption of intracellular activation
      are discussed. Basal levels of stimulated pro-inflammatory Il-6 levels are
      generally related to fatigue scores. However, in CFS patients this association is
      of greater magnitude and can also be observed for TNF-alpha.

PMID- 15471617
TI  - Habituation of cortisol responses to repeated psychosocial stress-further
      characterization and impact of genetic factors.
AB  - Although a rapid response habituation to repeated stress exposure is a key
      characteristic of the hypothalamus-pituitary-adrenal (HPA) axis, several studies
      document a substantial inter-individual variability of such HPA response
      patterns. In order to further investigate the individual differences in the
      habituation of this important neuroendocrine system to psychosocial stress, 54
      male twin pairs were exposed to moderate psychosocial stress on three occasions,
      each exposure separated by a 1-week interval. Additionally, an ACTH(1-24)
      stimulation test (1 microg) and a dexamethasone suppression test (0.5mg) were
      performed. Although on average the expected decrease of mean cortisol and ACTH
      responses across stress exposures was observed, only 52% of the subjects showed
      this well-documented general decline and almost 16% of the participants even
      showed a response sensitization across sessions. Furthermore, a weak habituation
      was related to low cortisol responses to both the first stress exposure as well
      as the ACTH challenge. Moreover, genetic analyses did not reveal any evidence for
      a substantial heritability of the individual cortisol response habituation or an
      association between this habituation and two common polymorphisms in the
      glucocorticoid receptor gene.

PMID- 15471618
TI  - Relationship between allopregnanolone and negative mood in postmenopausal women
      taking sequential hormone replacement therapy with vaginal progesterone.
AB  - OBJECTIVE: To compare severity of negative mood and physical symptoms between
      women with different progesterone, allopregnanolone, and pregnanolone plasma
      concentrations during sequential Hormone Replacement Therapy (HRT) with vaginal
      progesterone suppositories. DESIGN: A randomized, placebo-controlled, double
      blind, crossover study. METHOD: Postmenopausal women (n=36) with climacteric
      symptoms were treated with 2mg estradiol daily during three 28-day cycles.
      Vaginal progesterone suppositories with 400, 800 mg/day or placebo were added
      sequentially for 14 days per cycle. Daily symptom ratings using a validated
      rating scale were kept. Blood samples for progesterone, allopregnanolone, and
      pregnanolone radioimmunoassays were collected during each treatment cycle.
      RESULTS: Women were divided into three groups (low, medium, and high) based on
      plasma allopregnanolone concentration during progesterone treatment. The
      concentration of allopregnanolone in the medium group corresponds to the
      concentration seen during the mid luteal phase of the menstrual cycle. Within
      women with medium allopregnanolone concentration significantly more negative mood
      and physical symptoms were rated during progesterone treatment compared to
      treatment with unopposed estrogen or placebo. Between women significantly more
      negative mood symptoms were seen during progesterone treatment cycles with medium
      allopregnanolone concentration compared to cycles with low concentration. Plasma
      progesterone, allopregnanolone, and pregnanolone concentrations increased with
      increasing progesterone dose. Progesterone and allopregnanolone plasma
      concentrations increased 2h after vaginal administration of progesterone at 400
      and 800 mg/day. CONCLUSION: Vaginal progesterone in sequential HRT causes
      negative mood, most likely mediated via allopregnanolone.

PMID- 15471620
TI  - Dry matter intake and energy balance in the transition period.
AB  - It is easy, based on theoretic considerations, to make the argument that
      maximizing DMI is important to minimize postpartum complications and losses in
      milk production that may be associated with them. However, research over the past
      several years provides ample evidence that successful "passage" through the
      periparturient period is more complicated than simply maximizing feed intake.
      Anecdotal evidence from veterinarians and nutrition consultants also confirm that
      feeding low-NDF diets to achieve high prepartum feed intakes during the prefresh
      transition period does not necessarily solve fresh-cow problems. Perhaps more
      important than maximizing feed intake is to minimize the likelihood of cows
      experiencing large drops in feed intake immediately before parturition.
      Retrospective analysis of existing data sets indicates that this hypothesis has
      merit; research must be conducted to vigorously test it. Until then, it seems
      reasonable to try to achieve high DMI, if it can be sustained through
      parturition. If it cannot, perhaps a more conservative approach is to limit
      voluntary intake by increasing dietary fiber, because data suggests that cows fed
      in such a manner experience less dramatic decreases in feed intake as parturition
      approaches. We examined the importance of parity, body condition score, and
      various diet components that may influence DMI during the final 3 weeks before
      parturition, but they only explained 18% of the variation in intake among cows.
      Clearly, there are many other factors that affect intake that need to be
      identified. Aspects of farm management that may influence animal stress need to
      be investigated, particularly during the prefresh transition period when cows are
      inherently prone to reductions in feed intake.

PMID- 15471621
TI  - Macromineral disorders of the transition cow.
AB  - Four macrominerals have the distinction of being involved in the "downer cow"
      syndrome, which is, unfortunately, often associated with parturition in cows.
      Inadequate blood calcium (Ca), phosphorus (P), magnesium (Mg), or potassium (K)
      concentrations can cause a cow to lose the ability to rise to her feet because
      these minerals are necessary for nerve and muscle function. Less severe
      disturbances in blood concentrations of these minerals can cause reduced feed
      intake, poor rumen and intestine motility, poor productivity, and increased
      susceptibility to other metabolic and infectious disease. Mechanisms for
      maintaining blood Ca, P, Mg, and K concentrations perform efficiently most of the
      time, but occasionally these homeostatic mechanisms fail and metabolic diseases
      such as milk fever occur. Understanding how and why these mechanisms fail may
      allow the practitioner to develop strategies to avoid these disorders.

PMID- 15471622
TI  - Behavioral needs of the transition cow and considerations for special needs
      facility design.
AB  - Improved building designs come from a better understanding of the behavioral
      needs of the dairy cow. The costs to provide for these needs in the facility must
      be offset by improved milk production, health, and longevity. Research is still
      required to more fully understand the health implications of many building design
      considerations and their impact on disease. Perhaps the most important end result
      of an improved environment for the transition cow, however, is an improvement in
      animal well-being. Better buildings that accommodate the behavioral needs of cows
      present "win-win" situations where dairy cattle thrive and work is more
      enjoyable. This results in an improved image for the industry, greater consumer
      confidence in the quality and safety of the final food product, and a prosperous
      dairy industry.

PMID- 15471623
TI  - Managing the dairy cow at calving time.
AB  - Managing the dairy cow at calving, unlike artificial insemination or transrectal
      ultrasonography, is often perceived as an unskilled task, not requiring
      specialist training. This article presents the argument for the financial and
      welfare costs associated with poor periparturient management, and how to address
      them by veterinarian-led education and upskilling of herd personnel. Successful
      management of the dairy cow at calving will result in the birth of a healthy calf
      and a smooth transition of the cow into the milking string with minimal calving
      problems and their sequelae. The tenets of good calving management are predicting
      accurately when calving is due, moving cows to the maternity unit on time,
      discrete calving supervision, knowing when and how to intervene, and ensuring the
      calf is vigorous and fed colostrum and the cow is healthy postpartum.

PMID- 15471624
TI  - The importance of the nonlactating period in the epidemiology of intramammary
      infection and strategies for prevention.
AB  - The dry period is a high risk period for the acquisition of new environmental
      IMIs, with over 60% of new IMIs occurring at this time. It also offers an ideal
      opportunity to improve udder health, through the judicious use of antibiotics to
      treat high SCC cows. The prophylactic use of antibiotics in food producing
      animals is increasingly being called into question; DCT is the primary example of
      such antibiotic use in the dairy cow. A holistic approach to management of the
      dry cow is a vital part of mastitis control, and should encompass environmental
      and nutritional management as well as the blanket use of therapeutic and
      prophylactic medicinal products. In high SCC cows, it is important to select cows
      appropriate for treatment (as opposed to culling), and there is a good clinical
      justification for the use of antibiotics to treat existing IMIs. In low SCC cows,
      teat sealants provide a viable alternative to antibiotic DCT, and careful
      consideration should be given to their use.

PMID- 15471625
TI  - The postpartum uterus.
AB  - The cow is notable among the domestic species for the almost ubiquitous bacterial
      contamination of the uterine lumen after parturition and the high incidence of
      clinical uterine disease. Such uterine disease not only disrupts uterine tissues,
      but also ovarian follicle growth and function by perturbation of the
      hypothalamus, pituitary, and ovary. Other events such as the postpartum negative
      energy balance also have similar multilevel effects on postpartum endocrinology.
      Return of ovarian cyclical activity is dependent on the innate immune system
      resolving uterine bacterial contamination,prompt uterine involution, and a short
      interval to the negative energy balance nadir. Although the risk factors for
      uterine disease have been described, preventive strategies are not widely
      adopted. Thus, veterinarians must identify and treat uterine disease efficiently
      to limit their negative effect on fertility.

PMID- 15471626
TI  - Managing the production, storage, and delivery of colostrum.
AB  - Provision of an adequate immunoglobulin mass to dairy calves is an essential
      component for survival, health, and future productivity. To prevent FPT of
      immunity due to suckling of the dam, newborn dairy calves should be removed from
      the calving area within 30 minutes of birth. First and later lactation cows are
      suitable colostrum donors, provided they are healthy, well-vaccinated, have had
      optimal transition management, and an appropriate dry-period length. Early
      colostrum collection yields an adequate immunoglobulin mass provided that 3 to 4
      L of colostrum is fed to the newborn calf. Regular testing for the adequacy of
      the dairy's colostrum feeding program is an excellent way to prevent calf health
      problems and identify potential need for CSs or replacement products.

PMID- 15471627
TI  - Diagnosis and treatment programs for fresh cows.
AB  - There is a large amount of excitement and uncertainty about the management and
      nutrition of the transition cow. A good rule of thumb is that the more ways that
      are proposed to do something, the less certain it is which are correct. The wide
      range of opinions currently held on this subject probably means that our current
      knowledge about why fresh cows fail and how they should be treated and managed is
      inadequate. There is only one treatment for milk fever, and there are only two
      proper positions for a calf at calving. Yet fresh cow programs are proposed that
      range from intensive screening and treatment, including daily temperatures and
      drenching every fresh cow with a large amount of fluids, to nothing.

PMID- 15471628
TI  - Using herd records to monitor transition cow survival, productivity, and health.
AB  - There is no single monitor that can fully characterize the success of a
      transition cow management program in a herd. Rather we must rely on a group of
      key monitors. Table 5 outlines the key indices and targets that we use in herd
      investigations. By using these monitors, effective transition cow programs can be
      differentiated from problematic ones, and many of the problems can be resolved
      for the good of the herd owners, dairy laborers, and most of all, the cows.
      Development of more sophisticated monitors and software with stronger
      epidemiologic structure will allow for better analysis of programs in the future.

PMID- 15471629
TI  - Monitoring and testing dairy herds for metabolic disease.
AB  - Clinical impressions of metabolic disease problems in dairy herds can be
      corroborated with herd-based metabolic testing. Ruminal pH should be evaluated in
      herds showing clinical signs associated with SARA (lame cows, thin cows, high
      herd removals or death loss across all stages of lactation, or milk fat
      depression). Testing a herd for the prevalence of SCK via blood BHB sampling in
      early lactation is useful in almost any dairy herd, and particularly if the herd
      is experiencing a high incidence of displaced abomasum or high removal rates of
      early lactation cows. If cows are experiencing SCK within the first 3 weeks of
      lactation, then consider NEFA testing of the prefresh cows to corroborate
      prefresh negative energy balance. Finally, monitoring cows on the day of calving
      for parturient hypocalcemia can provide early detection of diet-induced problems
      in calcium homeostasis. If hypocalcemia problems are present despite
      supplementing anionic salts before calving, then it may be helpful to evaluate
      mean urinary pH of a group of the prefresh cows. Quantitative testing strategies
      based on statistical analyses can be used to establish minimum sample sizes and
      interpretation guidelines for all of these tests.

PMID- 15471630
TI  - Manipulating milk production in early lactation through photoperiod changes and
      milking frequency.
AB  - Photoperiod management and increased milking frequency in early lactation offer
      noninvasive methods to improve production and health in dairy cows. Prolactin
      physiology is critical to the responses, and thus may be a factor in other
      environmental effects (eg, temperature and stress). Integration of these
      strategies into the management system is not difficult, but requires attention to
      details of feeding, housing, and animal movement. The techniques can be combined
      effectively with other management strategies that increase milk yield. There is
      evidence that cows managed using photoperiod manipulation and frequent milking
      produce more milk than control animals, but also have improved transitions into
      lactation.

PMID- 15471631
TI  - Prospects for zero days dry.
AB  - Recent studies in high-producing dairy cows have demonstrated the dry period
      requirement is greatly influenced by parity and management practice. Multiparous
      cows that were continuously milked and treated with bST demonstrated negligible
      production losses in the next lactation. First-lactation heifers, however,
      demonstrated large reductions in milk yield. These reductions were not overcome
      by using bST or IMF the next lactation. No studies have been performed examining
      use of LDPP or SDPP in combination with bST and IMF on the dry-period
      requirement. Cows that are continuously milked demonstrated higher feed intakes
      during the peripartum period, which may greatly improve metabolic health. Future
      studies must examine potential benefits of continuous milking on health in the
      next lactation.

PMID- 15471632
TI  - [Amniotic fluid embolism].

PMID- 15471633
TI  - [Anaesthesia and intensive care for cardiac surgery in France: results of the
      three days national survey realised in 2001 by the club of Anaesthesia, Intensive
      Care and Technics in Cardiac Surgery (ARTECC)].
AB  - OBJECTIVES: Ageing of the surgical population and the evolution in anaesthetic
      techniques have led the Club d'anesthesie-reanimation et techniques en chirurgie
      cardiaque (ARTECC) to conduct a survey among French cardiac surgery centers. The
      aim was to profile patient population undergoing cardiac surgery and
      perioperative techniques employed. STUDY: National prospective study including
      all adult patients undergoing cardiac surgery on January 23rd, 24th and 25th,
      2001. Data were collected during the first 48 postoperative hours. MATERIAL AND
      METHODS: Seven referent centers drafted a record form. Sixty-one centers sent
      back 425 patient forms, 399 were analyzed. The following were statistically
      studied: type of surgery, patient characteristics, preoperative treatment,
      monitoring, anaesthesia, cardio-pulmonary bypass (CPB) characteristics, duration
      of mechanical ventilation, length of stay in intensive care unit, postoperative
      complications. RESULTS: Patient mean age was 64.3 +/- 13.3 years. Patients over
      80-year-old represented 2.5% of the population. Beating heart coronary aortic
      bypass grafts (13% surgery) and preoperative transoesophagal echography were not
      frequent. Propofol and sufentanil were the main anaesthetic agents used. There
      was a marked trend for fast-track procedures. CONCLUSIONS: The ARTECC study
      pointed out some reserve in practices and that the impact of new techniques seems
      limited. Regular use of studies of that kind will provide an effective tool to
      compare national practices.

PMID- 15471634
TI  - [Color M-mode Doppler for postoperative estimation of pulmonary capillary wedge
      pressure].
AB  - OBJECTIVE: The aim of this study was to evaluate the accuracy of the combined
      index E/Vp (peak E velocity combined with color M-mode color Doppler flow
      propagation) for estimating pulmonary capillary wedge pressure, in post cardiac
      surgery patients. STUDY DESIGN: Prospective clinical trial. PATIENTS AND METHODS:
      In post cardiac surgery patients (D1), we have measured with transthoracic
      echocardiography peak early E transmitral pulsed Doppler velocities and color M
      mode Doppler flow propagation velocity (Vp). The E/Vp ratio was compared with
      pulmonary capillary wedge pressure (PAPO) obtained simultaneously. RESULTS:
      Thirty eight patients were studied. The coefficient of correlation between PAPO
      and E/Vp was r = 0.71 (p < 0.0001). The sensitivity and the specificity of E/Vp >
      1.5 for prediction of PAPO > 15 mmHg were 79% and 79% respectively. CONCLUSION:
      In post cardiac surgery patients, PAPO can be reasonably estimated by measuring
      the ratio E/Vp obtained with Doppler echocardiography.

PMID- 15471635
TI  - [Survey on the use of mannitol in prehospital care in Paris area].
AB  - OBJECTIVE: To evaluate the use of mannitol in prehospital care in Paris area.
      STUDY DESIGN: Survey using telephone interviews. METHODS: Emergency physicians on
      duty in the 37 emergency departments in charge of prehospital care in Paris area
      were called by one investigator. They were asked to answer a questionnaire about
      their own use of mannitol in the prehospital setting. RESULTS: Ninety-six
      questionnaires were recorded. Physicians were anaesthesiologists (9%) or
      emergency physicians (87%). In three departments, mannitol was not available in
      the ambulances. Thirty-five per cent (n = 34) reported no use of mannitol and 17%
      (n = 16) just once. Fourteen physicians (15%) did not want to use it. The reasons
      for not using mannitol were lack of knowledge about efficacy for five, need for
      previous brain imaging for seven or neurosurgeon's agreement before using
      mannitol for three. For those who had already used mannitol or were ready to use
      it, the main indication was increased intracranial pressure with clinical signs
      of brain herniation after severe brain injury for 92% of physicians. Thirty-one %
      reported not knowing the dose of mannitol, 33% having a memorandum immediately
      available and among those who answered the question, 63% gave a value compatible
      with guidelines. CONCLUSION: A significant percentage of physicians tacking part
      in the French prehospital care system, do not follow published guidelines on the
      use of mannitol. Actions improving implementation of those guidelines should be
      supported.

PMID- 15471636
TI  - [Inhalation induction].
AB  - OBJECTIVES: To clarify how pharmacokinetics explains the speed and quality of
      mask induction with sevoflurane alone or associated with adjuvants. To describe
      the various techniques to obtain adequate anaesthesia for laryngeal mask or
      tracheal tube insertion. To give the indications, contra-indications and
      complications of this technique. DATA SOURCES: Data were obtained from Medline
      and authors clinical experience. DATA SYNTHESIS: Inhalation induction in adults
      affords rapid loss of consciousness similar to the intravenous route if high
      concentrations of sevoflurane are delivered to the patient. Time of laryngeal
      mask or tracheal tube insertion is longer but may be reduced by adding N(2)O
      and/or a low opioid dose. The interest of benzodiazepine as premedication is not
      established but is highly probable when considering its potentiating effect on
      halogenated agents. Without any adjuvant, inhalation induction maintains
      spontaneous ventilation better than propofol. This justifies favouring this
      technique when difficult intubation is anticipated. This technique is associated
      to less or similar cardiovascular effects than intravenous propofol. However,
      some patients exhibit dramatic tachycardia and arterial pressure increase that
      should lead to caution in cardiovascular disabled patients. This sympathetic
      hyperactivity occurs with epileptiform EEG activity that was never associated
      with postanaesthesia mental dysfunction. In aged or cardiac patients, by reducing
      sevoflurane concentrations from 8% to 2% (or by 2% decreasing steps), the
      cardiovascular effect of this inhalation induction is better than propofol. This
      technique is contra-indicated in HMS susceptible patients and those suffering
      from a myopathy, or patients with intracranial hypertension, a full stomach or
      active gastro-oesophageal reflux. CONCLUSION: Inhalation induction in adults
      remains little used in common clinical practice. Technical improvement by adding
      opioids and education of anesthetists should increase the diffusion of this
      alternative method to intravenous induction of anaesthesia.

PMID- 15471637
TI  - [Morbidity after cervicofacial cancer surgery].
AB  - Identification of specific risk factors by analysis of complications and new
      reconstructive surgical procedures has changed anaesthesia practice for
      cervicofacial cancer surgery. In spite of difficult airways and long duration of
      surgery, the incidence of complications is low. Adapted protocols for patients
      with cardiac or respiratory diseases allow the reduction of complication rate.
      Nevertheless, risk of early postoperative death persists and justifies careful
      monitoring during the first days after surgery. Incidence of local infection
      remains high.

PMID- 15471638
TI  - [Should adjuvant treatments (antiplatelet agents, anticoagulants, normovolaemic
      haemodilution and vasodilators) be used in cervicofacial and maxillofacial free
      flaps reconstructive surgery?].
AB  - The ENT and maxillo-facial reconstruction with free flaps has become a standard.
      The objective of the adjuvant treatments is to limit failures (approximately 6%)
      related to ischaemia/reperfusion. French surgical centres use specific protocols
      depending on the surgeon. They used antiplatelet agent, anticoagulants,
      normovolemic hamodilution and vasodilators. Many experimental studies are
      available. However, there is no clinical study to recommend the use of
      antiplatelet agents (combination with heparin increase the risk of pre- and
      postoperative bleeding), of normovolemic hemodilution (pulmonary oedema) and of
      vasodilators. After analysis of one of the only prospective study, we propose the
      use of heparin following a deep vein thrombosis preventive protocol. Due to the
      limited number of the patients and difficulty to have homogenous series, it is
      impossible to draw new recommendations, even if ischemic preconditioning
      techniques offer new research horizons.

PMID- 15471639
TI  - [Fatal amniotic fluid embolism. Extraction by Caesarean section of a living child
      without neurological after-effects].
AB  - The authors report on the case of an amniotic fluid embolism, proven by post
      mortem, which was the result of an inaugural and irreversible cardiac arrest in a
      37-year-old woman at 39 weeks of normal pregnancy. The Caesarean section was
      carried out as an extreme emergency in the labour room, while efforts were being
      made to resuscitate the mother, so as to deliver a living newborn without any
      neurological after-effects. The haemostatic consequences were showed up only on
      blood tests.

PMID- 15471640
TI  - [Abdominal aorta lesion during surgical treatment of a foraminal disk hernia].
AB  - We report a case of an abdominal aorta lesion on a 54-year-old woman, who
      underwent surgery for the treatment of a foraminal disk hernia. At the end of the
      hernia repair, a sudden hypovolaemic collapse occurred. A computed tomography
      revealed an abdominal aorta disruption and a retroperitoneal haematoma. An
      endovascular treatment was preferred to a surgical reintervention and an
      endoluminal stent-graft was inserted; the postoperative course was uneventful.
      This case report describes an example of vascular complications of disk hernia
      surgery which are rare but potentially serious. It emphasizes the increasing
      development of endovascular procedures and their utility in the treatment of
      acute contained aortic disruption.

PMID- 15471641
TI  - [Lung separation after reintubation with airway exchange catheter in multiple
      trauma patient with massive haemoptysis].
AB  - A 24-year-old man fell from the third floor. He developed an unilateral pulmonary
      parenchymal injury and a significant haemoptysis following blunt thoracic trauma.
      Because of its abundance, it was not possible to obtain adequat oxygenation. To
      protect controlateral lung from inhalation and to achieve adequat oxygenation, we
      used double lumen endotracheal tube, lung separation and one lung ventilation. To
      solve potential airway management difficulties (haemorrhage, trauma, cervical
      immobilization), we used airway exchange catheter (Cook) to place the double
      lumen endotracheal tube. Haemoptysis has been controlled by embolization of the
      right bronchial artery.

PMID- 15471642
TI  - Labor analgesia in a parturient with prior Harrington rod instrumentation: is
      caudal epidural an option?

PMID- 15471643
TI  - New onset Lambert-Eaton myasthenic syndrome as an unexpected cause of delayed
      recovery from general anesthesia after thyroidectomy.

PMID- 15471644
TI  - Peripartum care of the parturient with Indiana continent urinary diversion: a
      need for a multidisciplinary approach.

PMID- 15471645
TI  - [Treatment of an injured adult presenting with vertebral-medullary trauma].

PMID- 15471646
TI  - Oral methadone for cancer pain: no indication of Q-T interval prolongation or
      torsades de pointes.

PMID- 15471647
TI  - Places of cancer death in Germany.

PMID- 15471648
TI  - Agreement among family members in their assessment of the Quality of Dying and
      Death.
AB  - Improving end-of-life care requires accurate indicators of the quality of dying.
      The purpose of this study was to measure the agreement among family members who
      rate a loved one's dying experience. We administered the Quality of Dying and
      Death instrument to 94 family members of 38 patients who died in the intensive
      care unit. We measured a quality of dying score of 60 out of 100 points and found
      moderate agreement among family members as measured by an intraclass correlation
      coefficient (ICC) of 0.44. Variability on individual items ranged from an ICC of
      0.15 to 1.0. Families demonstrated more agreement on frequencies of events (ICC
      0.54) than on determinations of quality (ICC 0.32). These findings reveal
      important variability among family raters and suggest that until the variability
      is understood, multiple raters may generate more comprehensive end-of-life data
      and may more accurately reflect the quality of dying and death.

PMID- 15471649
TI  - Measuring hospice care: the National Hospice and Palliative Care Organization
      National Hospice Data Set.
AB  - Hospice has seen rapid growth in recent years, but there is a lack of consistency
      among hospices when it comes to compliance with standards of care. Consequently,
      hospices vary in performance and in services they provide. With state hospice
      organizations, the NHPCO developed a National Data Set (NDS) intended to
      understand demographics, practices, and outcomes; illustrate industry
      effectiveness; facilitate communication of industry legislative needs; and to
      support agency performance and improvement. Our paper describes development of
      the NDS and data that are being collected, and summarizes key findings from the
      2000, 2001, and 2002 NDS. The data collection process, which began in 1999, has
      evolved substantially over a 4-year period to the point that we believe the 2002
      NDS represents a well-designed core that will receive only minor modifications
      annually. This database will be invaluable for comparative audit, clinical
      practice and managing services because only that which is measured can be
      improved.

PMID- 15471650
TI  - Towards a new clinical tool for needs assessment in the palliative care of cancer
      patients: the PNPC instrument.
AB  - This study describes a new clinical tool for needs assessment in palliative care:
      the Problems and Needs in Palliative Care questionnaire (PNPC). It was developed
      to support the provision of care tailored to the specific demands of patients,
      which only can be provided when their needs are clearly identified. To test
      validity and reliability, 64 patients with metastatic cancer living at home
      completed the PNPC. Of 140 initial items, 2 were deleted because of low response.
      No important topics were missing. Dimensions were proposed to organize the
      problems and needs in a logical and practical array for use in individual
      patients, and to enable statistical analysis of patient-groups. Reliability
      analysis supported the proposed dimensions, with Cronbach's alpha coefficient
      >0.70 for dimensions with > or = 5 items, and alpha >0.65 for the 3- and 4-item
      dimensions. However, the dimensions 'physical symptoms' and 'social issues'
      lacked coherency with some low item-total correlations. The PNPC demonstrated
      convergent validity with the European Organization for Research and Treatment of
      Cancer (EORTC) and COOP-WONCA quality-of-life measures. These data are a first
      step in validating the PNPC, although the 'social issues' dimension needs
      reconsideration. Further studies are needed to evaluate clinical use.

PMID- 15471651
TI  - A population-based evaluation of an intervention to improve advanced stage cancer
      pain management.
AB  - The purpose of this study was to evaluate the effect of a community-oriented
      intervention in one part of the Free Town of Bremen, northern Germany (population
      541,000) on the prescription prevalence of World Health Organization (WHO) class
      III opioids for cancer patients in their final year of life. A community
      oriented, multimodal intervention included information, teaching, and training
      modules tailored to physicians, pharmacists, nursing staff, and patients and
      their relatives, and the public. Prescription prevalences were calculated for the
      intervention region (Bremen-Nord) and a control region (Bremen-Mitte) before and
      after the intervention. Specifically, a population-based, controlled,
      quantitative assessment of opioid prescriptions for patients with cancer during
      their final year of life was undertaken for two time periods, prior to 1992-1993
      and after 1995-1996, respectively. Prescription ascertainment was based on
      duplicates kept in the pharmacies. Patients comprised two anonymized complete 4
      month samples who died in 1993 and 1996, respectively, with cancer as the primary
      or a contributory cause of death on their death certificates. A total of 1282
      prescriptions were abstracted from duplicates in 109 of 119 pharmacies in Bremen
      Mitte and all 31 pharmacies in Bremen-Nord (overall pharmacy participation
      proportion 93%) and individually matched to 856 patients with cancer in their
      final year of life. In 1993, 16.3% of all terminal cancer patients in Bremen
      Mitte and 19.1% in Bremen-Nord had received at least one prescription for a WHO
      class III opioid. Corresponding numbers after the intervention were 20% and 21%,
      respectively. The total amount of class III opioids, however, increased 20% in
      Bremen-Mitte and 210% in Bremen-Nord after the intervention. In 1996, the
      spectrum of prescribed opioids had changed markedly toward the WHO
      recommendations. The proportion of prescribing physicians remained constant.
      These data suggest that a community-oriented intervention in one part of Bremen
      had a limited impact on cancer pain therapy on the population level. A measurable
      change of prescription practice seemed to be restricted to the minority of
      physicians, who had prior experience with prescribing WHO class III opioids.

PMID- 15471652
TI  - Considerations of healthcare professionals in medical decision-making about
      treatment for clinical end-stage cancer patients.
AB  - In order to determine which considerations healthcare professionals use in
      decision-making about treatment for inpatients with end-stage cancer, we observed
      110 discussions at multidisciplinary meetings at two oncology departments. The
      discussions concerned 74 patients. Thirty-three of the 110 discussions concerned
      potentially life-prolonging or life-shortening treatments. The most important
      decision-making considerations were chance of improvement, patient's treatment
      wishes, amount of suffering, and the chance of therapy being successful.
      Discussions resulted in 6 decisions that might shorten life, 10 decisions that
      might prolong life, and 23 postponements of decisions because of lack of
      information. These observations confirm that medical interventions with a
      possible life-prolonging or life-shortening effect are a frequently discussed
      issue in medical decision-making for end-stage cancer patients in The
      Netherlands. Before making a decision, healthcare professionals gather extensive
      information about what gain is to be expected from an intervention. When
      healthcare professionals establish that a decision would be medically
      appropriate, the patient's wish will often be an important consideration.

PMID- 15471653
TI  - Morphine for dyspnea control in terminal cancer patients: is it appropriate in
      Taiwan?
AB  - Morphine for dyspnea control usually arouses ethical controversy in terminal
      cancer care. This study prospectively assessed the use of morphine for dyspnea
      control in terminal cancer patients in terms of two characteristics: the extent
      to which medical staff, family, and patients found morphine to be ethically
      acceptable and efficacious, and the influence of morphine on survival. One
      hundred and thirty-six palliative care patients meeting specific eligibility
      criteria were enrolled. A structured data collection form was used daily to
      evaluate clinical conditions, which were analyzed at the time of admission and 48
      h before death. Sixty-six (48.6%) of the 136 patients had dyspnea on admission.
      The intensity was mild in 14.0% and moderate or severe in 34.6%. The intensity of
      dyspnea became worse 48 h before death (4.29+/-2.55 vs. 4.94+/-2.60, P < 0.001,
      range 0-10). Twenty-seven (40.9%) of 66 patients with dyspnea received morphine
      on admission for the control of dyspnea; the routes of administration were oral
      (59.3%) and subcutaneous (40.7%). Fewer than two-thirds (59.3%) of the patients
      were given morphine with the consent of both patient and family. More than one
      third (40.7%) on admission and about one-half (52.8%) in the 48 h before death
      had the consent of family alone. Positive ethical acceptability and satisfaction
      with using morphine for dyspnea control were found in both medical staff and
      family in this study. Multiple Cox regression analysis showed that using morphine
      for dyspnea, both on admission and in the 48 h before death, did not
      significantly influence the patients' survival (HR: 0.015, 95% CI: 0.00-4.23; HR:
      1.76, 95% CI: 0.73-4.24). In this population, the use of morphine for dyspnea
      control in the terminal phase of cancer was effective and ethically validated in
      the study. Research efforts to find the most appropriate route and dosage of
      morphine for dyspnea, based on the patient's situation, remain worthwhile.

PMID- 15471654
TI  - Frequency and perceived competence in providing palliative care to terminally ill
      patients: a survey of primary care physicians.
AB  - We surveyed primary care physicians about their involvement and perceived skills
      in palliative care. A survey instrument asked how frequently internal medicine
      and family practice physicians performed 10 palliative care items. Subjects rated
      their skills in each area. A majority of physicians always or frequently
      performed all 10 palliative care items, but fewer than 50% of respondents
      adequately attended to the spiritual needs and economic problems of patients.
      Interest in palliative care was associated with an increased frequency in
      performing palliative care items (P = 0.036), while training in palliative care
      was associated with better perceived performance (P = 0.05). Only 36% of
      respondents had received training in palliative care. Internists and family
      practitioners provide palliative care to patients, but feel their skills are
      lacking in certain areas. Training may improve care to patients at the end of
      life.

PMID- 15471655
TI  - Course of fatigue in women receiving chemotherapy and/or radiotherapy for early
      stage breast cancer.
AB  - Although much has been learned about the complication of fatigue during breast
      cancer treatment, the possibility that there are differences across treatment
      modalities in breast cancer patients' experience of fatigue has not yet been
      established. In this study, fatigue was assessed in 134 women receiving
      chemotherapy and radiotherapy or radiotherapy only for early stage breast cancer.
      Comparisons of fatigue during initial treatment indicated that women who received
      chemotherapy reported greater fatigue severity and disruptiveness than women
      receiving radiotherapy. Women not pre-treated with chemotherapy experienced
      increased fatigue over the course of radiotherapy. Results confirmed predictions
      that fatigue in women with early stage breast cancer differs as a function of the
      type of treatment and sequencing of treatment. Findings indicating increases in
      fatigue during radiotherapy only among women not pretreated with chemotherapy
      suggest a response shift, or a change in internal standards, in women's
      perceptions of fatigue as a function of prior chemotherapy treatment.

PMID- 15471656
TI  - Dexamethasone in addition to metoclopramide for chronic nausea in patients with
      advanced cancer: a randomized controlled trial.
AB  - Chronic nausea occurs in most patients with advanced cancer. This study was done
      to assess the antiemetic effects of dexamethasone in patients with chronic nausea
      refractory to metoclopramide. Secondary outcomes included appetite, fatigue, and
      pain. Fifty-one patients who had nausea (> or = 3/10 on a 0-10 scale) for > or =
      2 weeks despite 48 hours of oral metoclopramide therapy (40-60 mg/day) were
      enrolled. Patients received 20 mg/day dexamethasone (DM) orally (n = 25) or
      placebo (n = 26) for severe nausea in addition to metoclopramide (60 mg/day
      orally). At baseline the mean nausea intensity ratings in the DM and placebo
      groups were 8.0 and 7.4. At Day 8 they were 2.1 and 2.0, respectively. At Day 3
      and Day 8, the mean difference in nausea intensity for the DM and placebo groups
      was 4.5 and 2.9 (P = 0.16) and 5.9 and 5.7 (P = 0.85), respectively. Improvement
      in appetite and fatigue were observed on Day 3 and Day 8 in both groups as
      compared with the baseline. Pain, vomiting, well-being, and quality of life
      remained unchanged in both groups at both times. We conclude that DM was not
      superior to placebo in the management of chronic nausea in our patients with
      advanced cancer.

PMID- 15471657
TI  - Psychometric update of the Functional Interference Estimate: a brief measure of
      pain functional interference.
AB  - The Functional Interference Estimate (FIE) is a brief, 5-item self-report measure
      that assesses the degree to which pain interferes with daily functioning. While
      the FIE has demonstrated reliability and validity with a small normative sample,
      not much is known about its reliability and validity with a broad sample of
      individuals with pain. The current study presents FIE score means, variability
      estimates, reliability and validity data based on a large sample (n = 1,337) of
      primary care patients who report problematic pain. The FIE has excellent internal
      consistency and appears to have strong convergent validity with other well
      established measures of function (e.g., SF-36 and Dartmouth COOP Charts). Because
      of its brevity and flexibility, the FIE may be a useful self-report measure of
      pain functional interference in clinical research on pain.

PMID- 15471658
TI  - Treatment of postherpetic neuralgia: a review of therapeutic options.
AB  - Postherpetic neuralgia (PHN) is a disabling consequence of the reactivation of
      the varicella zoster infection. The observation that patients with PHN experience
      various types of pain suggests that multiple pathophysiologic mechanisms are
      involved, which may include the peripheral and central nervous systems. A
      reasonable initial strategy would involve selecting from among multiple agents
      that have complementary mechanisms of action and that have been proven effective
      in controlled clinical trials, such as the lidocaine patch 5%, gabapentin,
      tricyclic antidepressants, and opioids. Based on initial assessment and ongoing
      reassessment, sequential trials should be undertaken until adequate pain relief
      is achieved. This may ultimately lead to therapy with more than one medication.
      Safety and tolerability are important considerations in choosing initial therapy,
      particularly in older patients. Physicians can either add another agent to the
      current regimen or switch to a new type of monotherapy if there is inadequate
      response to initial therapy. Alternative therapies, (i.e., ketamine, intrathecal
      corticosteroid injections) have not been adequately studied. Well-designed,
      multicenter, controlled clinical trials are needed to develop a treatment
      algorithm that provides an evidence-based, rational approach to treating PHN.

PMID- 15471659
TI  - Aggressive pharmacological treatment for reversing malignant bowel obstruction.
AB  - Early and intensive pharmacological treatment not only may reduce
      gastrointestinal symptoms but also reverse malignant bowel obstruction. Fifteen
      consecutive advanced cancer patients with inoperable bowel obstruction received a
      combination of drugs including metoclopramide, octreotide, dexamethasone and an
      initial bolus of amidotrizoato. Recovery of intestinal transit was reported
      within 1-5 days in fourteen patients, who continued this treatment without
      presenting symptoms of bowel obstruction until death. This case series
      establishes that the combination of propulsive and antisecretive agents can act
      synergistically to allow a fast recovery of bowel transit without inducing
      unpleasant colic. It suggests that the most important mechanism in these
      circumstances is functional and can be reversible, if an aggressive treatment is
      initiated early before fecal impaction and edema render bowel obstruction
      irreversible.

PMID- 15471660
TI  - Performance improvement program for reducing home health care costs in hospice.

PMID- 15471661
TI  - CT screening for lung cancer Assessing a regimen's diagnostic performance.
AB  - PURPOSE: The purpose of this study was to characterize the diagnostic performance
      of a regimen of CT screening for lung cancer. METHODS: Using a common
      protocol/regimen of screening, 2968 asymptomatic persons at high risk for lung
      cancer were enrolled in two studies [Early Lung Cancer Action Projects (ELCAP) I
      and II] for baseline and annual repeat screening. A total of 4538 annual repeat
      screenings were performed. The regimen's diagnostic performance was characterized
      in terms of frequency of positive result of the initial CT as well as of screen
      diagnosis and Stage I screen-diagnosis among all diagnoses (interim-diagnoses
      included), all separately for baseline and annual repeat screenings. RESULTS: The
      proportions with positive result of the initial CT were 12% and 6% in the
      baseline and repeat screenings, respectively. The proportions of screen-diagnoses
      among all diagnoses (interim-diagnoses included) were 97% and 99% in the baseline
      and repeat cycles, respectively. The corresponding proportions of pre-surgical
      Stage I screen-diagnoses were 95% and 93%. CONCLUSION: The performance of the
      ELCAP regimen is quite satisfactory in avoiding over many positive results of the
      initial CT, and it produces highly promising diagnostic results as for the
      attainment of cure by early intervention.

PMID- 15471662
TI  - Solitary pulmonary nodules: optimal slice thickness of high-resolution CT in
      differentiating malignant from benign.
AB  - The purpose of this study was to determine an optimal slice thickness that was
      efficient in differentiating malignant from benign solitary pulmonary nodules
      (SPNs) on high-resolution computed tomography (HRCT) images. For a total of 92
      SPNs, four radiologist indicated their confidence level for the malignant or
      benign SPN on the CT images presented in 1-, 3-, and 5-mm slice thickness. HRCT
      could be used to differentiate more accurately the malignant nodules from the
      benign ones using 1-mm-thick sections than 3- or 5-mm-thick sections.

PMID- 15471663
TI  - CT evaluation of gastrointestinal tract perforation.
AB  - The purpose of this study is to review the computed tomography (CT) appearance of
      gastrointestinal tract (GI) perforation. Forty-two patients with 10 cases of
      proximal GI perforation and 32 cases of distal GI perforation were evaluated
      based on the CT findings of extraluminal air (which was subdivided into the CT
      falciform ligament sign crossing the midline and scattered pockets of air), bowel
      wall thickening (>8 mm in gastroduodenal wall, >3 mm in the small bowel wall, >6
      mm in the caliber of the appendix and >5 mm in the colonic wall), associated
      abscess formation, ascites and adjacent fat stranding. The results were compared
      using Fisher's Exact Test. Detection of extraluminal air in the upright plain
      films and CT was analyzed by Z test. Our results showed that CT-falciform
      ligament sign was more frequent in the proximal GI perforation, while pockets of
      extraluminal air (excluding the cases accompanying CT-falciform ligament sign),
      bowel wall thickening and fat stranding were found in higher incidence in distal
      GI perforation (P<.05). CT detected extraluminal air in more cases than the
      upright plain films did (69% vs. 19%; Z=4.62>Z(0.01)=2.326). We concluded that CT
      is a good imaging tool to differentiate the various GI perforations.

PMID- 15471664
TI  - Traumatic bowel perforation: analysis of CT findings according to the perforation
      site and the elapsed time since accident.
AB  - Abdominal CTs of 57 patients with bowel perforation after blunt abdominal trauma
      were retrospectively analyzed to determine: the diagnostic accuracy of the
      perforation site, and the differential findings according to the elapsed time
      from the trauma. Diagnostic accuracy of the perforation site was as follows:
      duodenum (100%), jejunum (81%), jejunoileal junction (100%), ileum (93%), and
      colon (20%). Extraluminal air was the only significant differential findings
      according to the elapsed time, and was seen more commonly on late stage of bowel
      perforation (P<.05).

PMID- 15471665
TI  - Computed tomography findings of peritoneal tuberculosis: systematic review of
      seven patients diagnosed in 6 years (1996-2001).
AB  - OBJECTIVE: The aim of this study was to describe the computed tomography (CT)
      findings in patients with demonstrated peritoneal tuberculosis (TB) and their
      concordance with the three types from the traditional classification (wet,
      fibrotic, and dry plastic). METHODS: We reviewed the CT images of all patients
      with microbiologically proven peritoneal tuberculosis over a 6-year period (1996
      2001). RESULTS: Seven patients were included. Ascites was present in 5 patients
      (free ascites in 3 patients and loculated in 2). Involvement of the mesentery was
      found in 5 patients, the omentum in 4, and the parietal peritoneum in 3.
      Tuberculous lymphadenitis was the most common associated finding (6 patients).
      Two patients had hepatic lesions. The fibrotic type was found in all the
      patients, and 5 patients had an association of the fibrotic and wet types. None
      of the patients had lesions consistent with the dry plastic type. CONCLUSION:
      Peritoneal tuberculosis is best described as a combination of ascites, peritoneal
      lesions, and lymphadenopathy, rather than the three types from the traditional
      classification.

PMID- 15471666
TI  - Radiology-Pathology Conference: Bilateral renal oncocytomas.
AB  - Oncocytoma is an uncommon benign, typically solitary renal tumor first reported
      in 1942. Renal oncocytomas are rarely multiple and/or bilateral. Accurate
      preoperative diagnosis and differentiation from renal carcinoma is difficult. We
      report the radiology and pathology of a patient with bilateral renal oncocytomas
      and review the literature of this rare presentation.

PMID- 15471667
TI  - Multiple hypervascular pancreatic metastases from renal cell carcinoma: dynamic
      MR and spiral CT in three cases.
AB  - Pancreatic metastases are rare. Melanoma, lung cancer and breast carcinoma are
      the most common origin of pancreatic metastases, whereas renal cell carcinoma is
      counted in only 1-2%. Renal cell carcinoma usually leads to a solitary pancreatic
      metastasis, whereas multiple pancreatic metastases are uncommon. We present three
      cases of multiple hypervascular pancreatic metastases from renal cell carcinoma,
      studied with spiral CT and dynamic MR.

PMID- 15471668
TI  - Screening for abdominal aortic aneurysms during routine lumbar CT scan:
      modification of the standard technique.
AB  - INTRODUCTION: Abdominal aortic aneurysms (AAAs) are often incidental findings in
      patients undergoing US, CT or MRI studies. The recommended field of view (FOV)
      for standard CT examinations of the spine is 14 cm. This FOV does not allow full
      visualization of the abdominal aorta. PURPOSE: To justify a larger FOV for male
      smokers older than 55 years and women older than 65 years, with a higher
      incidence of AAA. MATERIALS AND METHODS: The lumbar CT examinations of 100
      consecutive patients (age: mean 68 years, range 55-85 years) presented with low
      back pain were retrospectively reviewed. Measurements of the abdominal aorta and
      lumbar abnormalities were analysed. A control study in 850 patients who underwent
      abdominal CT scans for other causes was available for comparison. RESULTS: There
      were three men with AAAs measuring 4.5, 5.5 and 5.6 cm (mean 5.2 cm). Findings
      related to the clinical problem were disk prolapse or herniation, spondylosis,
      spinal stenosis and grade I spondylolesthesis. In the control group, 17 patients
      were found with AAAs with diameter greater than 4 cm (2%). CONCLUSIONS: Patients
      with low-back pain, older than 55 years of age, examined with lumbar spine CT,
      should also be screened for aortic disease, since the prevalence of AAA is
      similar with that of an age-matched control group. Appropriate modification in
      the applied FOV is recommended.

PMID- 15471669
TI  - Enlarged vomeronasal organ in a child: imaging findings.
AB  - The vomeronasal organ is a special sensory organ that exists in both animals and
      humans. It is located on the sides of nasal septum and although it involutes with
      age, occasionally it may be seen in humans. We present the imaging findings in a
      child with an enlarged nasal septum whose features we believe are compatible with
      a vomeronasal organ.

PMID- 15471670
TI  - Computed tomography in TN stage evaluation of oral cavity and oropharyngeal
      cancers.
AB  - Oral and oropharyngeal carcinomas are characterized by a high incidence of node
      metastatic involvement and local extension. The study compared the TN stage of
      patients by clinical and computed tomography (CT) examination to postoperative
      histopathology. Sensitivity of CT for tumor extension was 82%, predictive value
      for bone involvement 67%. Clinical examination was poor in predicting the
      presence (54%) or absence (56%) of node involvement. Sensitivity of CT for
      assessment of node involvement was 80%, specificity 71%, positive predictive
      value 67%, and negative 83%. Node involvement was high (30%) in clinically NO
      necks versus only 9% for negative CT.

PMID- 15471671
TI  - Thyroid calcifications: sonographic patterns and incidence of cancer.
AB  - We investigated the incidence of cancer in surgically resected 151 thyroid
      nodules in 101 patients according to their calcification patterns on preoperative
      ultrasonography (US). Calcification was detected in 57 (38%) nodules, 31 (54%) of
      which was histologically diagnosed as cancer. According to the calcification
      types, 9 of 11 nodules with microcalcifications, 15 of 29 nodules with
      intranodular coarse calcification, 6 of 14 nodules with peripheral calcification
      and 1 of 3 calcified spots without surrounding tumor were diagnosed as cancer.

PMID- 15471672
TI  - Imaging evaluation of meniscal injury of the knee joint: a comparative MR imaging
      and arthroscopic study.
AB  - To evaluate the efficacy of MR imaging in the diagnosis and classification of
      meniscal tear of the knee joint, we retrospectively characterized the MR features
      of 78 meniscal tears in 148 patients according to the Mesgarzadeh's criteria. The
      results showed that the sensitivity and specificity for meniscal tears were 92%
      and 87%, respectively. Type VI meniscal tear was the most common type, especially
      in displaced meniscal tear. MR is a reliable diagnostic tool for meniscal tears
      and associated cruciate ligament injury.

PMID- 15471673
TI  - Carotid-anterior cerebral artery anastomosis: MR angiographic features and
      literature review.
AB  - Carotid-anterior cerebral artery anastomosis is a rare anomaly of the anterior
      part of the circle of Willis. We report here magnetic resonance (MR) angiographic
      findings in 2 patients with this anomaly. MR angiographic source images are
      useful in evaluating the anatomical details of this anomaly. Including the 2
      present cases, 27 patients with this anomaly have been reported in the English
      language literature. Thirty anomalous arteries were found in the 27 patients
      (R/L/bilateral=22/2/3). The reason for the right-sided predominance is unknown.

PMID- 15471674
TI  - Subependymoma in the third ventricle in a child.
AB  - Subependymomas are rare, slow-growing, benign intraventricular tumors which occur
      commonly in the fourth or lateral ventricle. They usually occur in elderly men
      and often are asymptomatic and discovered incidentally. We report a case of a 6
      year-old girl with a symptomatic subependymoma in the third ventricle with MR
      imaging.

PMID- 15471675
TI  - Temporal variation in the specific dynamic action of juvenile New Zealand rock
      lobsters, Jasus edwardsii.
AB  - To enhance the on-growing of Jasus edwardsii in culture, it is important to
      understand the feeding physiology of juveniles. In crustaceans, there is a loss
      of energy and an increase in oxygen consumption (specific dynamic action or SDA)
      associated with feeding. The present research measured the SDA of juvenile J.
      edwardsii fed either in the morning or at night held at 15 degrees C. Closed box
      respirometry was used to measure oxygen consumption (MO(2)) and ammonia excretion
      in juvenile lobsters. Juveniles exhibited a nocturnal rhythm in both MO(2) and
      ammonia excretion. The factorial rise in MO(2) (1.58+/-0.03 times) for lobsters
      fed in the morning was significantly less than lobsters fed at night (1.80+/-0.01
      times). Lobsters fed in the morning had a significantly shorter SDA (30+/-1.2 h)
      response compared to lobsters fed at night (36+/-1 h). Energy loss as a result of
      digestion was less for lobsters fed in the morning. Therefore, if juvenile J.
      edwardsii are fed in the morning, they could optimise the energy content of the
      meal and this could result in increased growth.

PMID- 15471676
TI  - Anti-peroxidation effects of vitamin E on low density lipoprotein and milk fat
      globule membrane of lactating goats: in vivo versus metal ion challenge in vitro.
AB  - Ruminants are animals with mild oxidation risk considering characteristics of
      their plasma. The purpose of the present study was to determine if surplus
      vitamin E supplementation further improved their peroxidation status. Four
      lactating goats (Capra ibex ibex) receiving a single intramuscular injection of
      3000 IU d-alpha-tocopheryl acetate were monitored daily for a week. Plasma and
      milk levels of thiobarbituric acid reactive substances (TBARS) were measured to
      estimate the peroxidation status of overall body and mammary gland, respectively.
      Lipid hydroperoxide content of low density lipoprotein (LDL) and milk fat globule
      membrane (MFGM) were determined both immediately after isolation and after metal
      ion challenge to evaluate their spontaneous peroxidation in vivo and peroxidation
      susceptibility in vitro, respectively. The results showed that while plasma and
      milk levels of alpha-tocopherol peaked at day 2, the corresponding TBARS dropped
      to their lowest weekly levels. Content of preformed lipid hydroperoxides in LDL
      and MFGM remained unchanged (P>0.05) during the study period, while peroxidation
      in LDL and MFGM on extended exposure to Cu(2+) was prevented by vitamin E
      enrichment. Therefore, surplus vitamin E was beneficial to the peroxidation
      resistant mechanisms of the overall body and those specifically within mammary
      gland of lactating goats. Furthermore, peroxidation resistance of LDL and MFGM to
      copper challenge in vitro also benefited from vitamin E enrichment despite the
      fact their endogenous peroxidation seemed unresponsive. The hypothesis that
      peroxidation of LDL and MFGM of lactating goats in situ, which proceeds with
      metal ion-independent mechanisms, is minor was discussed.

PMID- 15471677
TI  - Isolation and characterization of enterocytes along the intestinal tract of the
      gilthead seabream (Sparus aurata L.).
AB  - Epithelial cells were successfully isolated along the intestine of the gilthead
      seabream using a dissociation method based on intracellular-like solutions.
      Biochemical and physiological tests revealed highly viable cells from all
      intestinal segments. Image analysis was used to identify cell types in the
      epithelial preparations which were highly enriched in enterocytes (>95%) over
      mucous cells. Several digestive hydrolases were determined in the isolated cells.
      Maltase (M), sucrase (S), leucine aminopeptidase (LA), 5'nucleotidase (5'N), but
      not gamma-glutamyl transferase (gamma-GT) or alkaline phosphatase (AP) activities
      were found to be enriched in the epithelial preparations versus the corresponding
      intestinal homogenates. Comparison of digestive hydrolases revealed the existence
      of a clear heterogeneity in their expression pattern in the enterocytes, along
      the intestine. Na(+)-K(+)-ATPase, Na(+)-ATPase and Cl(-)-ATPase activities were
      also determined in the membrane fraction of isolated cells. Analyses of enzymatic
      profiles revealed a clear asymmetry in the distribution of all Mg(2+)-dependent
      ATPases; that is, maximal Na(+)-K(+)- and Na(+)-ATPase activities were observed
      in the enterocytes from pyloric caeca, while Cl(-)-ATPase activity was about
      twice as high in the enterocytes from anterior and posterior intestines compared
      with pyloric caeca. This is the first report demonstrating the existence of
      heterogeneous metabolic and enzymatic profiles in different enterocyte
      populations from euryhaline teleosts.

PMID- 15471679
TI  - Response of the haematocrit to body condition changes in Northern Bald Ibis
      Geronticus eremita.
AB  - We study the usefulness of the haematocrit as a predictor of body condition in
      birds, using a captive population of the endangered species Northern Bald Ibis
      (Geronticus eremita). This population is 14% of the worldwide captive population,
      which is far greater than the known free-living population. The haematocrit, body
      mass and body condition index responded in the same sense to two different
      nutritional periods, and there was a statistically significant relationship
      between changes in condition index and haematocrit of individual birds between
      the two periods. We discuss the relationship of these parameters with
      subcutaneous fat and muscle mass, and analyse the individuals' nutritional status
      in each of the periods studied. The conclusion was that the haematocrit is
      sensitive to variations in body condition since it responds to mass-loss
      processes corresponding to phases of mobilization of fat reserves, a situation
      prior to the mobilization of muscle proteins when there is a manifest
      deterioration of the individual's aspect.

PMID- 15471678
TI  - Influence of the photocycle and thermocycle on rhythms of plasma thyroxine and
      plasma and ocular melatonin in late metamorphic stages of the bullfrog tadpole,
      Rana catesbeiana.
AB  - The diel fluctuations in plasma thyroxine (T(4)) and plasma and ocular melatonin
      entrain to the light/dark (LD) cycle in the bullfrog tadpole, although the phase
      of the rhythms changes during development. Previous studies on the rhythmicity of
      these hormones were conducted under various LD cycles, but with a constant
      temperature, raising the question of the role of the natural thermocycle in
      determining the phase of the rhythms, and the changes that occur in the hormone
      levels and rhythms during late metamorphosis. To study this question, tadpoles
      were acclimated to simulated natural conditions of 14.5L:9.5D with a
      corresponding thermocycle in which the thermophase was 28 degrees C and the
      cryophase was 18 degrees C, or to the same thermocycle under constant light
      (24L). On both photoregimens, the diel fluctuations changed between
      prometamorphosis and metamorphic climax. However, more statistically significant
      rhythms, as indicated by the cosinor, occurred on 14.5L:9.5D than on 24L. At
      climax on the LD cycle, all hormones peaked around the same time in the late
      scotocryophase, whereas on 24L, plasma T(4) peaked in the thermophase and plasma
      and ocular melatonin peaks occurred some distance from each other early in the
      cryophase. The earlier peaks of plasma and ocular melatonin on 24L were due to a
      transient rise in these hormones at the onset of the cryophase, which was not
      sustained in the absence of an LD cycle. On 14.5L:9.5D with a corresponding
      thermocycle, the hormone rhythms had nearly the same phases as was found in
      previous work on 12L:12D at a constant temperature of 22 degrees C, allowing for
      minor phase shifting due to the photocycle differences, indicating that in this
      species laboratory studies on constant temperature give valid results even in the
      absence of a thermocycle. The findings show that the phases of the hormone
      rhythms are determined by the LD cycle although the onset of the cryophase, in
      the absence of a photocycle, may exert some influence on the nighttime rise in
      melatonin. The developmental rise in plasma T(4), and drop in plasma melatonin,
      occurred on both 14.5L:9.5D and 24L, indicating, taken together with previous
      work, that these climactic changes were independent of temperature and light
      cycling.

PMID- 15471680
TI  - Air breathing of the neotropical fishes Lepidosiren paradoxa, Hoplerythrinus
      unitaeniatus and Hoplosternum littorale during aquatic hypoxia.
AB  - The present study investigated the respiratory rates, frequency of air breathing
      and ability to extract oxygen from air compared to body mass of three neotropical
      air-breathing fishes (Lepidosiren paradoxa, Hoplerythrinus unitaeniatus and
      Hoplosternum littorale) with different accessory organs, under the same
      conditions of hypoxia (PO(2)<5 mm Hg) and temperature (25 degrees C), using the
      same apparatus. The results indicated a superior capacity of H. littorale (16.01
      ml O(2) breath(-1) kg(-1)) compared to H. unitaeniatus (7.03 ml O(2) breath(-1)
      kg(-1)) and L. paradoxa (4.95 ml O(2) breath(-1) kg(-1)).

PMID- 15471681
TI  - Development of the renal sexual segment in immature snakes: effect of sex steroid
      hormones.
AB  - The renal sexual segment (RSS) of immature Northern and Diamondback Water Snakes
      and Red-Sided Garter Snakes exhibited varying responses to testosterone or 17beta
      estradiol. In both male and female water snakes, kidney mass was not a reliable
      indicator of hormone treatment, whereas tubule diameter, epithelial height and
      number of sexual granules responded to hormone treatment. In male water snakes,
      either hormone initiated granule development by day 16; by day 23, only
      testosterone increased granule density. Female water snakes receiving either
      hormone exhibited a small number of granules by day 16; by day 23, granules
      increased only in Diamondback Water Snakes receiving testosterone. Hormones did
      not initiate RSS hypertrophy in female Red-Sided Garter Snakes. Tubule diameter
      and epithelial height of testosterone-treated males exhibited significant
      hypertrophy, while 17beta-estradiol initiated significant increases in tubule
      diameter. Garter snakes initiated sexual granule development in response to
      hormone treatment with males exhibiting a greater response than females and
      testosterone stimulating a greater response than 17beta-estradiol. Sex steroids
      appear to mimic sexual maturity in immature snakes initiating RSS development.
      Whereas the RSS of adult males respond to testosterone, our data suggest specific
      changes in the RSS of females during maturation effectively negates the effect of
      17beta-estradiol evident in immature female RSS.

PMID- 15471682
TI  - Digestion of cellulose and xylan by symbiotic bacteria in the intestine of the
      Indian flying fox (Pteropus giganteus).
AB  - Bats (Order Chiroptera) are a widely distributed group of mammals. Pteropus
      giganteus belongs to the Suborder Megachiroptera. This bat consumes fruits and
      leaves as their major food. Cellulose and xylan are the major composition of
      leaves. As they consume leaves in their diet, their digestive tract must contain
      cellulolytic and xylanolytic bacteria which help in the digestion of cellulose
      and xylan. The cellulolytic and xylanolytic bacteria were isolated and screened
      on Berg's agar containing cellulose and xylan. The bacteria isolated were
      characterized biochemically and found to be Proteus vulgaris, Proteus mirabilis,
      Citrobacter freundii, Serratia liquefaciens and Klebsiella oxytoca. These
      bacteria help in digestion of cellulose and xylan in the diet of the bat, P.
      giganteus. Here we show that leaves are also used as a carbohydrate source by
      these bats. An insectivorous bat, Hipposideros fulvus, was used as a control and
      does not possess cellulolytic and xylanolytic bacteria.

PMID- 15471683
TI  - Water balance and kidney function in the least shrew (Cryptotis parva).
AB  - We assessed renal function in least shrews (Cryptotis parva, body mass 4.7 g)
      within the context of overall water balance. The glomerular filtration rate (GFR)
      of shrews with unlimited food and water was 2.4 ml/h, about 60% of the rate
      predicted from body mass. Of this, about 3% (0.075 ml/h) was excreted as urine
      with an osmolality of 1944 mmol/kg, 5.5 times plasma osmolality. Shrews had a
      total water turnover (5 ml/day) two to three times higher than expected from
      allometry for a small mammal of this size. Water influx was partitioned among
      preformed water from food (65%), drinking (16%), and metabolic water (20%). Water
      efflux was divided among urine flow (35%), fecal water loss (estimated as 23%),
      and evaporation (by difference, 42%). Least shrews had a high water turnover rate
      and relatively high urine flow rate (UFR); this likely reflects a combination of
      factors, including high metabolism, active lifestyle, and wet diet.

PMID- 15471684
TI  - The relationship between body size and the field potentials generated by swimming
      crayfish.
AB  - Aquatic animals generate electrical field potentials which may be monitored by
      predators or conspecifics. Many crustaceans use rapid, forceful contractions of
      the flexor and extensor muscles to curl and extend their abdomens during swimming
      in escape and locomotion. When crayfish swim they generate electrical field
      potentials that can be recorded by electrodes nearby in the water. In general, it
      is reasonable to assume that larger bodied crayfish will generate signals of
      greater amplitude because they have larger muscles. It is not known, however, how
      activity in particular muscles and nerves combines to produce the compound
      electrical waveform recorded during swimming. We therefore investigated the
      relationship between abdominal muscle, body size and the amplitude of nearby
      tailflip potentials in the freshwater crayfish (Cherax destructor). We found that
      amplitude was correlated positively with abdominal muscle mass. The mean
      amplitude recorded from the five smallest and five largest individuals differed
      by 440 microV, a difference sufficiently large to be of significance to predators
      and co-inhabitants in the wild.

PMID- 15471685
TI  - Scaling the amplitudes of the circadian pattern of resting oxygen consumption,
      body temperature and heart rate in mammals.
AB  - We questioned whether the amplitudes of the circadian pattern of body temperature
      (T(b)), oxygen consumption (V (O(2))) and heart rate (HR) changed systematically
      among species of different body weight (W). Because bodies of large mass have a
      greater heat capacitance than those of smaller mass, if the relative amplitude
      (i.e., amplitude/mean value) of metabolic rate was constant, one would expect the
      T(b) oscillation to decrease with the increase in the species W. We compiled data
      of T(b), V (O(2)) and HR from a literature survey of over 200 studies that
      investigated the circadian pattern of these parameters. Monotremata, Marsupials
      and Chiroptera, were excluded because of their characteristically low metabolic
      rate and T(b). The peak-trough ratios of V (O(2)) (42 species) and HR (35
      species) averaged, respectively, 1.57+/-0.08, and 1.35+/-0.07, and were
      independent of W. The daily high values of T(b) did not change, while the daily
      low T(b) values slightly increased, with the species W; hence, the high-low T(b)
      difference (57 species) decreased with W (3.3 degrees C.W(-0.13)). However, the
      decrease in T(b) amplitude with W was much less than expected from physical
      principles, and the high-low T(b) ratio remained significantly above unity even
      in the largest mammals. Thus, it appears that in mammals, despite the huge
      differences in physical characteristics, the amplitude of the circadian pattern
      is a fixed (for V (O(2)) and HR), or almost fixed (for T(b)), fraction of the 24
      h mean value. Presumably, the amplitudes of the oscillations are controlled
      parameters of physiological significance.

PMID- 15471686
TI  - Assimilation efficiency of Rhinoceros Auklet (Cerorhinca monocerata) chicks fed
      Japanese anchovy (Engraulis japonicus) and Japanese sand lance (Ammodytes
      personatus).
AB  - We investigated the assimilation efficiency (AE) of a piscivorous alcid,
      Rhinoceros Auklet (Cerorhinca monocerata), chicks when fed Japanese anchovy
      (Engraulis japonicus) and Japanese sand lance (Ammodytes personatus), which are
      their main prey species. The assimilation efficiency corrected for nitrogen
      retention (NR) of the chicks fed sand lance (81.6%) was significantly higher than
      those fed anchovy (78.0%). The values of assimilation efficiencies for both fish
      species are similar to those of fish-fed seabird adults and fledglings.

PMID- 15471687
TI  - Modulation of ion uptake across posterior gills of the crab Chasmagnathus
      granulatus by dopamine and cAMP.
AB  - Cyclic AMP (cAMP) and dopamine modulate ion uptake across isolated and perfused
      posterior gills of Chasmagnathus granulatus acclimated to 10 per thousand
      salinity. Addition of cAMP agonists, such as cp-cAMP, forskolin, and IBMX,
      produced a significant increase in the transepithelial potential difference
      (Vte), which reflects ion transport activity. Dopamine (DA) also had a
      stimulatory effect on ion uptake, increasing Vte and Na(+) influx, although this
      effect was transient, since both variables remained elevated for less than 30
      min. In addition, the dose-response curve for DA concentration-Vte was biphasic,
      and the maximum stimulation was obtained with 10 micromol l(-1). When the effects
      of forskolin and DA on the Na(+)/K(+)-ATPase activity were tested, they
      correlated well with the Vte and Na(+) influx experiments; the enzyme activity
      increased significantly after preincubation of gill fragments for 10 min with
      forskolin or DA (51 and 64%, respectively), but there was no effect after pre
      incubation with DA for 20 min. Finally, KT5720, a specific inhibitor of cAMP
      dependent protein kinase (PKA), completely abolished the stimulatory effect of DA
      on Vte, suggesting the involvement of PKA in this mechanism.

PMID- 15471688
TI  - Lung collapse among aquatic reptiles and amphibians during long-term diving.
AB  - Numerous aquatic reptiles and amphibians that typically breathe both air and
      water can remain fully aerobic in normoxic (aerated) water by taking up oxygen
      from the water via extrapulmonary avenues. Nevertheless, if air access is
      available, these animals do breathe air, however infrequently. We suggest that
      such air breathing does not serve an immediate gas exchange function under these
      conditions, nor is it necessarily related to buoyancy requirements, but serves to
      keep lungs inflated that would otherwise collapse during prolonged submergence.
      We also suggest that lung deflation is routine in hibernating aquatic reptiles
      and amphibians in the northern portions of their ranges, where ice cover prevents
      surfacing for extended periods.

PMID- 15471689
TI  - Kinematic parameters of the walking of herons, ground-feeders, and waterfowl.
AB  - The kinematic gait characteristics of six species of birds in three groups were
      compared. The groups studied were herons (Gray Herons and Little Egrets), ground
      feeders (Domestic Pigeons and Gray Starlings), and waterfowl (Pintails and Black
      headed Gulls). The results showed that the relative stride frequency was greater
      in the waterfowl than in the other species. Complementary to this, the amplitude
      of the movements was smaller in the waterfowl than in the others. These
      differences between the waterfowl and the other species might be caused by their
      morphological and/or physiological adaptation to swimming. Another possible cause
      for these differences was the magnitude of head bobbing, as the ground-feeders
      and herons, which walk with head bobbing, showed a large relative stride length
      and excursion angle, while the waterfowl, which do not head-bob, walk with a
      relatively short stride length and small excursion angle. Moreover, the relative
      magnitude of head movement during walking was especially large in Little Egrets,
      which showed an especially large relative stride length and excursion angle.
      These parameters may have some mechanical relationships with each other.

PMID- 15471690
TI  - Bi-directional flow sensor with a wide dynamic range for medical applications.
AB  - This paper describes a novel three-wire thermal flow sensor for medical
      applications. The present innovation for low-frequency measurements involves the
      use of a pulsed-wire anemometer with a comparatively large wire diameter (12.5
      microm and larger) together with a novel signal processing approach. A small wire
      is heated using a sinusoidal alternating current, and two sensing wires, acting
      as resistance thermometers, are set parallel to, and at a small distance on
      either side of, the pulsed wire. The thermal wake of the pulsed wire is convected
      downstream to one of the two receiving wires which detect its delayed arrival.
      This arrangement allows the sensing of both the direction and the flow velocity
      component normal to the three probes. By appropriate signal processing, the
      present sensor can be operated such that the phase shift between the periodic
      current that drives the central wire and the detected signal by either the
      upstream or downstream wire takes into account a combination of convection,
      diffusion and the finite thermal response time of both the pulsed wire and the
      receiving wire. Because the time constants increase as the flow velocity
      decreases, the time lag due to thermal inertia supplements the time lag due to
      the true time of flight, thus yielding an effective operating range of 0.05 m/s
      <or= U <or= 25 m/s , which corresponds to a dynamic range of 500:1. This wide
      velocity range is an order of magnitude larger than that for the traditional time
      of-flight pulsed-wire anemometers. An important application of the bi-directional
      thermal flowmeter is the measurement of human respiration, e.g. for early
      diagnostics of asthmatic attacks. The main advantage of the present sensor is its
      low sensitivity to variations in temperature and also to the composition of the
      flowing gas. Also, a calibration will be not needed for each density and gas used
      in addition to that for velocity. The resultant design work aimed at developing a
      sensor that can be mass-produced at low cost.

PMID- 15471691
TI  - The effects of rocker sole and SACH heel on kinematics in gait.
AB  - The rocker sole and solid-ankle cushion-heel (SACH) heels are the most commonly
      prescribed external shoe modification. Only a limited number of scientific
      evidence exists to support these interventions in clinical practice. The
      objective of this study was to determine the effects of rocker soles and SACH
      heels on kinematics during gait. In this study, we investigated the gait
      parameters during level walking, stair climbing and stair descending in healthy
      volunteers and assessed the effects of the modified shoes on the motion of the
      forefoot and hindfoot compared with the traditional shoes. Eleven normal subjects
      participated in this study. A six-camera motion analysis system was used to
      capture motion trajectories. The three-dimensional (3D) coordinates of the
      markers were used to calculate the angles of flexion-extension, valgus-varus, and
      internal-external rotation at the hindfoot and forefoot joints in a gait cycle by
      the custom software for foot kinematic analysis. The results showed that the
      rocker soles offer several advantages from the viewpoint of gait kinematics. The
      forefoot joint excursion in sagittal plane while wearing rocker shoes was
      significantly less than that while wearing traditional shoes during level
      walking, stair climbing and stair descending. It means that they could mimic the
      action of the forefoot joint, aid in roll off, and simulate forefoot
      dorsiflexion. Since the bony structures mechanically link the forefoot joint and
      hindfoot joint to a triplanar axis of motion, they could be used whenever there
      is minimal or no motion at the forefoot joint or hindfoot joint, because of, for
      example, fusion, fracture, cast immobilization, orthosis design, pain, or
      arthritis.

PMID- 15471692
TI  - Comparison of compact bone failure under two different loading rates:
      experimental and modelling approaches.
AB  - Understanding the mechanical behaviour of bones up to failure is necessary for
      diagnosis and prevention of accident and trauma. As far as we know, no authors
      have yet studied the tensile behaviour of compact bone including failure under
      dynamic loadings (1 m/s). The originality of this study comes from not only the
      analysis of compact bone failure under dynamic loadings, the results of which are
      compared to those obtained under quasi-static loadings, but also the development
      of a statistical model. We developed a protocol using three different devices.
      Firstly, an X-ray scanner to analyse bone density, secondly, a common tensile
      device to perform quasi-static experiments, and thirdly, a special device based
      upon a hydraulic cylinder to perform dynamic tests. For all the tests, we used
      the same sample shape which took into account the brittleness of the compact
      bone. We first performed relaxation and hysteresis tests followed by tensile
      tests up to failure. Viscous and plastic effects were not relevant to the compact
      bone behaviour so its behaviour was considered elastic and brittle. The bovine
      compact bone was three to four times more brittle under a dynamic load than under
      a quasi-static one. Numerically, a statistical model, based upon the Weibull
      theory, is used to predict the failure stress in compact bone.

PMID- 15471693
TI  - Finite element modeling of the contact interface between trans-tibial residual
      limb and prosthetic socket.
AB  - Finite element method has been identified as a useful tool to understand the load
      transfer mechanics between a residual limb and its prosthetic socket. This paper
      proposed a new practical approach in modeling the contact interface with
      consideration of the friction/slip conditions and pre-stresses applied on the
      limb within a rectified socket. The residual limb and socket were modeled as two
      separate structures and their interactions were simulated using automated contact
      methods. Some regions of the limb penetrated into the socket because of socket
      modification. In the first step of the simulation, the penetrated limb surface
      was moved onto the inner surface of the socket and the pre-stresses were
      predicted. In the subsequent loading step, pre-stresses were kept and loadings
      were applied at the knee joint to simulate the loading during the stance phase of
      gait. Comparisons were made between the model using the proposed approach and the
      model having an assumption that the shape of the limb and the socket were the
      same which ignored pre-stress. It was found that peak normal and shear stresses
      over the regions where socket undercuts were made reduced and the stress values
      over other regions raised in the model having the simplifying assumption.

PMID- 15471694
TI  - Circumferential force production of the thumb.
AB  - We developed an apparatus to measure maximal continuous circumferential forces of
      a digit in the transverse plane that is perpendicular to the longitudinal axis.
      Subjects with asymptomatic hands were asked to produce maximal forces in all
      directions at the proximal phalanx of the thumb. The force components during
      circumferential trials were used to construct a force envelope for each subject.
      The force envelope enlarged as the number of trials increased, and converged to a
      stable pattern after several trials. The shape of the force envelope was
      asymmetric and oblique, skewed towards the flexion/adduction direction. Maximal
      force (112.1 +/- 14.8 N) was generated in the direction combining flexion and
      adduction. The lowest force produced was only 50.3% of the maximal force in a
      direction combining extension and abduction. The forces in the direction of
      adduction, extension, abduction, and flexion were 60.1%, 61.9%, 51.5%, and 92.9%
      of the maximal force, respectively. The forces generated by circumferential
      exertions were comparable to the forces by focused directional exertions except
      in the flexion direction. Our methods have the potential to identify deviations
      from the normative force output pattern and help detect underlying impairments
      resulting from neuromuscular disorders.

PMID- 15471695
TI  - Design and fabrication of custom mandible titanium tray based on rapid
      prototyping.
AB  - During the past few years, the combination of medical imaging and rapid
      manufacturing technique has proven to be a very important development. On the
      other hand, the conventional method has some drawbacks. For example, it takes
      longer time to complete an operation and it also presents some difficulty in
      matching the repaired contours. With advanced software and hardware, an image of
      an undamaged bone similar to that of the patient can be made from computerised
      tomography (CT); and a physical object constructed by the mirror-processed image
      data can be quickly fabricated with a high degree of fitting with the patient's
      bone. This paper presents a methodology for the design and fabrication of an
      individual titanium tray for the repair of mandible defects. Methods for the tray
      modeling using CAD system are presented: A 3D model of the bony defect is
      generated after the acquisition of helical CT data. An individual tray is
      designed using freeform surfaces geometries and fabricated by rapid prototyping
      (RP) technology. The results of tray filling with bone-grafting materials are
      then presented. RESULT: the tray is inserted into the patient mandible segment.
      The symmetry and reconstruction quality contour of the repaired mandible was
      satisfactory. Thus, the patient is able to eat normally. The bone-grafting
      material harvested from the anterior ilium was low. The clinical experience
      showed that rapid prototyping and reverse engineering software are effective
      methods of fabricating custom trays for mandibular reconstruction after bone loss
      due to a tumor.

PMID- 15471696
TI  - Stiffness properties for Nucleus standard straight and contour electrode arrays.
AB  - Trauma and damage during insertion of electrode arrays into the human cochlea are
      strongly related to the stiffness of the array. The stiffness properties of
      electrode arrays, which were determined by three-point flexural bending and
      buckling tests, are reported in this paper. To date there has been limited
      publication on mechanical properties of these electrode arrays. Previous studies
      mainly focused on characterizing the stiffness of the tip of the Nucleus straight
      array with little emphasis on characterizing the stiffness of its whole length.
      In this study, stiffnesses of the Nucleus straight and contour electrode arrays
      have been determined along their length. Young's modulus of elasticity of the
      Nucleus straight array has been found to increase from the tip (182 MPa) to the
      rear end (491 MPa), whereas the stiffness of the contour array is greatest near
      the tip (480 MPa) and is fairly uniform in the middle and rear sections of the
      electrode array (380-400 MPa). Buckling experiments have shown that the contour
      array has much higher critical buckling load (about four times) than the Nucleus
      straight array. The results from three-point flexural bending and buckling
      experiments provide significant data for the development of electrode arrays,
      from which new array designs with improved flexibility can be developed. The
      results of stiffness properties are also important input for use in finite
      element models to predict the trajectories during insertion and to help evaluate
      the effects of different electrode array designs on damage sustained during
      insertion.

PMID- 15471697
TI  - Mechanical and optical characteristics of a new fiber optical system used for
      cardiac contraction measurement.
AB  - In order to obtain a better physiological performance and a closer restoration of
      the regular rhythm of failing hearts, a new fiber optical sensor system for the
      measurement of cardiac contraction has been developed. It consists of an opto
      electrical unit and a sensing fiber which has to be positioned in the heart. The
      objective of this new fiber optic sensor system is to use the inotropic
      information to adjust a stimulation algorithm in single or multichamber pacing or
      to detect arrhythmia in insufficient heart function. In this study, the
      mechanical and optical characteristics of different fibers are investigated. The
      relationship between the attenuation (with an achieved numerical maximum of 0.3
      dB), the bending diameter and the angle of bending is determined in a range of 20
      160 mm. The most suitable fiber for the application in cardiological problems is
      determined (WT8 fiber), for which the sensitivity is analyzed. Additionally,
      power spectra are calculated from WT8 fiber signals obtained from pig hearts,
      working under physiological conditions. The maximal frequency response was 23 Hz.
      It is concluded that the fiber optical measurement of cardiac contraction is not
      only feasible and reproducible, but the WT8 fiber also shows optimal behavior in
      the range of parameters occurring in the heart chambers. Nevertheless, in order
      to restrict the measured signal reliably to bending processes within the chambers
      only, it is concluded that a special combined fiber has to be constructed with a
      high sensitivity only at its terminal section within the heart.

PMID- 15471698
TI  - Mass drug administration to eliminate lymphatic filariasis in India.
AB  - Mass drug administration (MDA) to eliminate lymphatic filariasis is already in
      place in 32 out of 83 endemic countries. Expansion of the MDA programme to other
      countries and within large countries such as India is necessary to achieve the
      goal of lymphatic filariasis elimination. However, expansion and sustenance of
      the global campaign to eliminate lymphatic filariasis requires commitment and
      allocation of funds by governments and donor agencies. This could be achieved, at
      least to some extent, by highlighting the benefits of the programme in relation
      to costs. On the basis of various studies in south India, this article assesses
      the costs, effectiveness and economic and social benefits of the MDA programmes
      aimed at eliminating lymphatic filariasis.

PMID- 15471699
TI  - Laser microdissection microscopy in parasitology: microscopes meet thermocyclers.
AB  - The new methods of laser microdissection microscopy have received wide acceptance
      in biology and have been applied in a small number of parasitology
      investigations. Here, the techniques and applications of laser microdissection
      microscopy are reviewed with suggestions of how the systems might be used to
      explore applied questions in parasite molecular biology and host-parasite
      interactions.

PMID- 15471700
TI  - Chemical ecology of insect vectors: the neglected temporal dimension.

PMID- 15471701
TI  - The surface-mosaic model in host-parasite relationships.
AB  - The dynamics of protein adsorption to a microbial surface could be of
      significance in host-parasite relationships because non-defense proteins might
      interfere with the binding of defense proteins. A surface mosaic of defense and
      non-defense proteins formed on the microbial surface could activate one of the
      tissue reactivity programs via a binary code (help or silence) generated by the
      adsorbed proteins. Understanding the mechanisms of the mosaic formation and its
      evolution might help to identify evasion mechanisms used by virulent
      microorganisms. This also provides a conceptual framework to design new
      strategies to control the infectious diseases they cause.

PMID- 15471702
TI  - The origins of antimalarial drug resistance.
AB  - Resistance of Plasmodium falciparum to the antimalarial drug sulfadoxine
      pyrimethamine is a result of extremely rare mutations that have spread over large
      geographical areas. This pattern was completely unexpected because mutations
      encoding resistance occur commonly in laboratory conditions, leading to the
      expectation that resistance would originate locally on numerous occasions. This
      can be reconciled with basic P. falciparum biology and epidemiology, and it is
      concluded that this pattern of extremely rare mutations and subsequent spread
      should be regarded as the most likely pattern of resistance to future
      antimalarials. Consequently, strategies to slow the spread of resistance need to
      be designed on regional, rather than national, considerations.

PMID- 15471703
TI  - Candidate protein selection for diagnostic markers of African trypanosomiasis.
AB  - The ability to accurately diagnose the presence of an infective micro-organism is
      not only important for individual human and animal health and wellbeing, but is
      also central to surveillance programmes. Effective and sustainable control of
      many diseases in the developing world depends on the availability of field
      applicable diagnostics that are cheap, reliable, simple in design and
      application, and which provide immediate results. This review examines how the
      genome sequences can be used in the selection of potential candidate proteins for
      developing new serodiagnostics for African trypanosomiasis.

PMID- 15471704
TI  - Macrophages, pathology and parasite persistence in experimental visceral
      leishmaniasis.
AB  - Many infectious diseases are associated with parasite persistence, often
      restricted to certain tissue sites, yet the determinants of such persistence are
      poorly understood. Infection with the protozoan parasite Leishmania donovani has
      proved a useful experimental tool to address how immune responses can be
      differentially effective in clearing parasites from different tissues and,
      conversely, it might also provide a good model for understanding the basis of
      parasite persistence. This article reviews recent studies on the determinants and
      consequences of persistent parasite infection in the spleen and suggest that some
      of the messages to emerge could have important implications for the study of a
      broad range of infectious diseases.

PMID- 15471705
TI  - Zoonotic protozoa: from land to sea.
AB  - Attention to worldwide pollution of the coastal marine environment has focused
      primarily on toxic algal blooms and pathogenic bacteria that multiply in nutrient
      rich waters. However, massive but unseen amounts of feces from humans, their
      pets, and their domesticated animals are discharged, dumped, or carried in
      runoff, bringing encysted zoonotic protozoan parasites to estuaries and coastal
      waters. Here, they contaminate bathing beaches, are filtered and concentrated by
      shellfish eaten by humans and marine mammals, and infect a wide range of marine
      animal hosts, resulting in morbidity and mortality to some populations. This
      review addresses the extent of contamination and the animals affected by three
      genera of important zoonotic protozoa: Giardia, Cryptosporidium and Toxoplasma.

PMID- 15471706
TI  - Evaluating the epidemiological impact of national control programmes for
      helminths.
AB  - During the past decade, there has been renewed commitment to programmes for
      helminth control, and several international initiatives have been launched.
      Scientific evaluation of large-scale interventions to reduce the incidence of
      infection and associated morbidity and mortality is vital, not only to
      demonstrate health benefits, but also to assess cost-effectiveness to show that
      monies from donor agencies have been used wisely. Using the example of
      schistosomiasis, this article outlines a framework for the evaluation of the
      impact of national control programmes, highlighting the important epidemiological
      and practical issues that must be addressed.

PMID- 15471707
TI  - Embracing scrutiny.

PMID- 15471708
TI  - The National Children's Study: a critical national investment.

PMID- 15471710
TI  - Association between air pollution and adverse pregnancy outcomes in Vancouver.

PMID- 15471711
TI  - Study on failures to disclose conflicts of interest in Environmental Health
      Perspectives.

PMID- 15471712
TI  - Bhopal: no silver linings.

PMID- 15471717
TI  - Childhood leukemia, military aviation facilities, and population mixing.

PMID- 15471718
TI  - The opposite of obesity: undernutrition overwhelms the world's children.

PMID- 15471719
TI  - Mission: educational.

PMID- 15471720
TI  - Setting a new syllabus: environmental health science in the classroom.
AB  - Environmental health is a subject that has only relatively recently become
      prominent in the social consciousness. Even as its significance becomes known,
      finding ways to integrate the subject into education for primary and secondary
      students is difficult because of federal testing requirements under the No Child
      Left Behind Act of 2001 and other demands placed on teachers. A number of efforts
      are under way, however, to provide teachers with resources to help them bring
      environment health into their classrooms.

PMID- 15471721
TI  - The fat of the land: do agricultural subsidies foster poor health?
AB  - Since the 1920s, American farmers have received various forms of federal support
      in an effort to keep farmers farming and provide Americans with an affordable,
      stable food supply. Wheat, soybeans, and especially corn are currently the most
      highly subsidized crops; products made from these crops, including high-fructose
      corn syrup and hydrogenated fats, have flooded the market as cheap means for
      making foods tastier, though not healthier. Now critics are asking whether
      subsidies for these crops are actually driving the U.S. epidemic of obesity.

PMID- 15471723
TI  - Application of benzo(a)pyrene and coal tar tumor dose-response data to a modified
      benchmark dose method of guideline development.
AB  - Assessment of cancer risk from exposure to polycyclic aromatic hydrocarbons
      (PAHs) has been traditionally conducted by applying the conservative linearized
      multistage (LMS) model to animal tumor data for benzo(a)pyrene (BaP), considered
      the most potent carcinogen in PAH mixtures. Because it has been argued that LMS
      use of 95% lower confidence limits on dose is unnecessarily conservative, that
      assumptions of low-dose linearity to zero in the dose response imply clear
      mechanistic understanding, and that "acceptable" cancer risk rests on a policy
      decision, an alternative cancer risk assessment approach has been developed.
      Based in part on the emerging benchmark dose (BMD) method, the modified BMD
      method we used involves applying a suite of conventional mathematical models to
      tumor dose-response data. This permits derivation of the average dose
      corresponding to 5% extra tumor incidence (BMD0.05) to which a number of
      modifying factors are applied to achieve a guideline dose, that is, a daily dose
      considered safe for human lifetime exposure. Application of the modified BMD
      method to recent forestomach tumor data from BaP ingestion studies in mice
      suggests a guideline dose of 0.08 microg/kg/day. Based on this and an
      understanding of dietary BaP, and considering that BaP is a common contaminant in
      soil and therefore poses human health risk via soil ingestion, we propose a BaP
      soil guideline value of 5 ppm (milligrams per kilogram). Mouse tumor data from
      ingestion of coal tar mixtures containing PAHs and BaP show that lung and not
      forestomach tumors are most prevalent and that BaP content cannot explain the
      lung tumors. This calls into question the common use of toxicity equivalence
      factors based on BaP for assessing risk from complex PAH mixtures. Emerging data
      point to another PAH compound--H-benzo(c)fluorene--as the possible lung
      tumorigen.

PMID- 15471724
TI  - Quinones and aromatic chemical compounds in particulate matter induce
      mitochondrial dysfunction: implications for ultrafine particle toxicity.
AB  - Particulate pollutants cause adverse health effects through the generation of
      oxidative stress. A key question is whether these effects are mediated by the
      particles or their chemical compounds. In this article we show that aliphatic,
      aromatic, and polar organic compounds, fractionated from diesel exhaust particles
      (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses
      showed that the quinone-enriched polar fraction was more potent than the
      polycyclic aromatic hydrocarbon (PAH)-enriched aromatic fraction in O2 .-
      generation, decrease of membrane potential (Delta-Psi m), loss of mitochondrial
      membrane mass, and induction of apoptosis. A major effect of the polar fraction
      was to promote cyclosporin A (CsA)-sensitive permeability transition pore (PTP)
      opening in isolated liver mitochondria. This opening effect is dependent on a
      direct effect on the PTP at low doses as well as on an effect on Delta-Psi m at
      high doses in calcium (Ca2+)-loaded mitochondria. The direct PTP effect was
      mimicked by redox-cycling DEP quinones. Although the aliphatic fraction failed to
      perturb mitochondrial function, the aromatic fraction increased the Ca2+
      retention capacity at low doses and induced mitochondrial swelling and a decrease
      in Delta-Psi m at high doses. This swelling effect was mostly CsA insensitive and
      could be reproduced by a mixture of PAHs present in DEPs. These chemical effects
      on isolated mitochondria could be reproduced by intact DEPs as well as ambient
      ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles
      failed to exert mitochondrial effects. These results suggest that DEP and UFP
      effects on the PTP and Delta-Psi m are mediated by adsorbed chemicals rather than
      the particles themselves.

PMID- 15471725
TI  - Acute infections and environmental exposure to organochlorines in Inuit infants
      from Nunavik.
AB  - The Inuit population of Nunavik (Canada) is exposed to immunotoxic
      organochlorines (OCs) mainly through the consumption of fish and marine mammal
      fat. We investigated the effect of perinatal exposure to polychlorinated
      biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) on the incidence of
      acute infections in Inuit infants. We reviewed the medical charts of a cohort of
      199 Inuit infants during the first 12 months of life and evaluated the incidence
      rates of upper and lower respiratory tract infections (URTI and LRTIs,
      respectively), otitis media, and gastrointestinal (GI) infections. Maternal
      plasma during delivery and infant plasma at 7 months of age were sampled and
      assayed for PCBs and DDE. Compared to rates for infants in the first quartile of
      exposure to PCBs (least exposed), adjusted rate ratios for infants in higher
      quartiles ranged between 1.09 and 1.32 for URTIs, 0.99 and 1.39 for otitis, 1.52
      and 1.89 for GI infections, and 1.16 and 1.68 for LRTIs during the first 6 months
      of follow-up. For all infections combined, the rate ratios ranged from 1.17 to
      1.27. The effect size was similar for DDE exposure but was lower for the full 12
      month follow-up. Globally, most rate ratios were > 1.0, but few were
      statistically significant (p < 0.05). No association was found when postnatal
      exposure was considered. These results show a possible association between
      prenatal exposure to OCs and acute infections early in life in this Inuit
      population.

PMID- 15471726
TI  - Does particulate air pollution contribute to infant death? A systematic review.
AB  - There is now substantial evidence that both short- and long-term increases in
      ambient air pollution are associated with increased mortality and morbidity in
      adults and children. Children's health is particularly vulnerable to
      environmental pollution, and infant mortality is still a major contributor to
      childhood mortality. In this systematic review we summarize and evaluate the
      current level of epidemiologic evidence of an association between particulate air
      pollution and infant mortality. We identified relevant publications using
      database searches with a comprehensive list of search terms and other established
      search methods. We included articles in the review according to specified
      inclusion criteria. Fifteen studies met our inclusion criteria. Evidence of an
      association between particulate air pollution and infant mortality in general was
      inconsistent, being reported from locations with largely comparable pollution
      levels. There was some evidence that the strength of association with particulate
      matter differed by subgroups of infant mortality. It was more consistent for
      postneonatal mortality due to respiratory causes and sudden infant death
      syndrome. Differential findings for various mortality subgroups within studies
      suggest a stronger association of particulate air pollution with some causes of
      infant death. Research is needed to confirm and clarify these links, using the
      most appropriate methodologies for exposure assessment and control of
      confounders.

PMID- 15471727
TI  - Drinking-water nitrate, methemoglobinemia, and global burden of disease: a
      discussion.
AB  - On behalf of the World Health Organization (WHO), I have undertaken a series of
      literature-based investigations examining the global burden of disease related to
      a number of environmental risk factors associated with drinking water. In this
      article I outline the investigation of drinking-water nitrate concentration and
      methemoglobinemia. The exposure assessment was based on levels of nitrate in
      drinking water greater than the WHO guideline value of 50 mg/L. No exposure
      response relationship, however, could be identified that related drinking-water
      nitrate level to methemoglobinemia. Indeed, although it has previously been
      accepted that consumption of drinking water high in nitrates causes
      methemoglobinemia in infants, it appears now that nitrate may be one of a number
      of co-factors that play a sometimes complex role in causing the disease. I
      conclude that, given the apparently low incidence of possible water-related
      methemoglobinemia, the complex nature of the role of nitrates, and that of
      individual behavior, it is currently inappropriate to attempt to link illness
      rates with drinking-water nitrate levels.

PMID- 15471728
TI  - Arsenic on the hands of children after playing in playgrounds.
AB  - Increasing concerns over the use of wood treated with chromated copper arsenate
      (CCA) in playground structures arise from potential exposure to arsenic of
      children playing in these playgrounds. Limited data from previous studies
      analyzing arsenic levels in sand samples collected from CCA playgrounds are
      inconsistent and cannot be directly translated to the amount of children's
      exposure to arsenic. The objective of this study was to determine the
      quantitative amounts of arsenic on the hands of children in contact with CCA
      treated wood structures or sand in playgrounds. We compared arsenic levels on the
      hands of 66 children playing in eight CCA playgrounds with levels of arsenic
      found on the hands of 64 children playing in another eight playgrounds not
      constructed with CCA-treated wood. The children's age and duration of playtime
      were recorded at each playground. After play, children's hands were washed in a
      bag containing 150 mL of deionized water. Arsenic levels in the hand-washing
      water were quantified by inductively coupled plasma mass spectrometry. Our
      results show that the ages of the children sampled and the duration of play in
      the playgrounds were similar between the groups of CCA and non-CCA playgrounds.
      The mean amount of water-soluble arsenic on children's hands from CCA playgrounds
      was 0.50 microg (range, 0.0078-3.5 microg). This was significantly higher (p <
      0.001) than the mean amount of water-soluble arsenic on children's hands from non
      CCA playgrounds, which was 0.095 microg (range, 0.011-0.41 microg). There was no
      significant difference in the amount of sand on the children's hands and the
      concentration of arsenic in the sand between the CCA and non-CCA groups. The
      higher values of arsenic on the hands of children playing in the CCA playgrounds
      are probably due to direct contact with CCA-treated wood. Washing hands after
      play would reduce the levels of potential exposure because most of the arsenic on
      children's hands was washed off with water. The maximum amount of arsenic on
      children's hands from the entire group of study participants was < 4 microg,
      which is lower than the average daily intake of arsenic from water and food.

PMID- 15471729
TI  - Effect of breast milk lead on infant blood lead levels at 1 month of age.
AB  - Nursing infants may be exposed to lead from breast milk, but relatively few data
      exist with which to evaluate and quantify this relationship. This route of
      exposure constitutes a potential infant hazard from mothers with current ongoing
      exposure to lead as well as from mothers who have been exposed previously due to
      the redistribution of cumulative maternal bone lead stores. We studied the
      relationship between maternal breast milk lead and infant blood lead levels among
      255 mother-infant pairs exclusively or partially breast-feeding through 1 month
      of age in Mexico City. A rigorous, well-validated technique was used to collect,
      prepare, and analyze the samples of breast milk to minimize the potential for
      environmental contamination and maximize the percent recovery of lead. Umbilical
      cord and maternal blood lead were measured at delivery; 1 month after delivery
      (+/- 5 days) maternal blood, bone, and breast milk and infant blood lead levels
      were obtained. Levels of lead at 1 month postpartum were, for breast milk, 0.3
      8.0 microg/L (mean +/- SD, 1.5 +/- 1.2); maternal blood lead, 2.9-29.9 microg/dL
      (mean +/- SD, 9.4 +/- 4.5); and infant blood lead, 1.0-23.1 microg/dL (mean +/-
      SD, 5.5 +/- 3.0). Infant blood lead at 1 month postpartum was significantly
      correlated with umbilical cord (Spearman correlation coefficient rS = 0.40, p <
      0.0001) and maternal (rS= 0.42, p < 0.0001) blood lead at delivery and with
      maternal blood (rS= 0.67, p < 0.0001), patella rS = 0.19, p = 0.004), and breast
      milk (rS = 0.32, p < 0.0001) lead at 1 month postpartum. Adjusting for cord blood
      lead, infant weight change, and reported breast-feeding status, a difference of
      approximately 2 microg/L (ppb; from the midpoint of the lowest quartile to the
      midpoint of the highest quartile) breast milk lead was associated with a 0.82
      microg/dL increase in blood lead for breast-feeding infants at 1 month of age.
      Breast milk lead accounted for 12% of the variance of infant blood lead levels,
      whereas maternal blood lead accounted for 30%. Although these levels of lead in
      breast milk were low, they clearly have a strong influence on infant blood lead
      levels over and above the influence of maternal blood lead. Additional
      information on the lead content of dietary alternatives and interactions with
      other nutritional factors should be considered. However, because human milk is
      the best and most complete nutritional source for young infants, breast-feeding
      should be encouraged because the absolute values of the effects are small within
      this range of lead concentrations.

PMID- 15471730
TI  - Outdoor, indoor, and personal exposure to VOCs in children.
AB  - We measured volatile organic compound (VOC) exposures in multiple locations for a
      diverse population of children who attended two inner-city schools in
      Minneapolis, Minnesota. Fifteen common VOCs were measured at four locations:
      outdoors (O), indoors at school (S), indoors at home (H), and in personal samples
      (P). Concentrations of most VOCs followed the general pattern O approximately
      equal to S < P less than or equal to H across the measured microenvironments. The
      S and O environments had the smallest and H the largest influence on personal
      exposure to most compounds. A time-weighted model of P exposure using all
      measured microenvironments and time-activity data provided little additional
      explanatory power beyond that provided by using the H measurement alone. Although
      H and P concentrations of most VOCs measured in this study were similar to or
      lower than levels measured in recent personal monitoring studies of adults and
      children in the United States, p-dichlorobenzene was the notable exception to
      this pattern, with upper-bound exposures more than 100 times greater than those
      found in other studies of children. Median and upper-bound H and P exposures were
      well above health benchmarks for several compounds, so outdoor measurements
      likely underestimate long-term health risks from children's exposure to these
      compounds.

PMID- 15471731
TI  - The association between asthma and allergic symptoms in children and phthalates
      in house dust: a nested case-control study.
AB  - Global phthalate ester production has increased from very low levels at the end
      of World War II to approximately 3.5 million metric tons/year. The aim of the
      present study was to investigate potential associations between persistent
      allergic symptoms in children, which have increased markedly in developed
      countries over the past three decades, and the concentration of phthalates in
      dust collected from their homes. This investigation is a case-control study
      nested within a cohort of 10,852 children. From the cohort, we selected 198 cases
      with persistent allergic symptoms and 202 controls without allergic symptoms. A
      clinical and a technical team investigated each child and her or his environment.
      We found higher median concentrations of butyl benzyl phthalate (BBzP) in dust
      among cases than among controls (0.15 vs. 0.12 mg/g dust). Analyzing the case
      group by symptoms showed that BBzP was associated with rhinitis (p = 0.001) and
      eczema (p = 0.001), whereas di(2-ethylhexyl) phthalate (DEHP) was associated with
      asthma (p = 0.022). Furthermore, dose-response relationships for these
      associations are supported by trend analyses. This study shows that phthalates,
      within the range of what is normally found in indoor environments, are associated
      with allergic symptoms in children. We believe that the different associations of
      symptoms for the three major phthalates-BBzP, DEHP, and di-n-butyl phthalate-can
      be explained by a combination of chemical physical properties and toxicologic
      potential. Given the phthalate exposures of children worldwide, the results from
      this study of Swedish children have global implications.

PMID- 15471732
TI  - Estimated risk for altered fetal growth resulting from exposure to fine particles
      during pregnancy: an epidemiologic prospective cohort study in Poland.
AB  - The purpose of this study was to estimate exposure of pregnant women in Poland to
      fine particulate matter [less than or equal to 2.5 microm in diameter (PM 2.5)]
      and to assess its effect on the birth outcomes. The cohort consisted of 362
      pregnant women who gave birth between 34 and 43 weeks of gestation. The
      enrollment included only nonsmoking women with singleton pregnancies, 18-35 years
      of age, who were free from chronic diseases such as diabetes and hypertension. PM
      2.5 was measured by personal air monitoring over 48 hr during the second
      trimester of pregnancy. All assessed birth effects were adjusted in multiple
      linear regression models for potential confounding factors such as the size of
      mother (maternal height, prepregnancy weight), parity, sex of child, gestational
      age, season of birth, and self-reported environmental tobacco smoke (ETS). The
      regression model explained 35% of the variability in birth weight (beta = -200.8,
      p = 0.03), and both regression coefficients for PM 2.5 and birth length (beta = 
      1.44, p = 0.01) and head circumference (HC; beta = -0.73, p = 0.02) were
      significant as well. In all regression models, the effect of ETS was
      insignificant. Predicted reduction in birth weight at an increase of exposure
      from 10 to 50 microg/m3 was 140.3 g. The corresponding predicted reduction of
      birth length would be 1.0 cm, and of HC, 0.5 cm. The study provides new and
      convincing epidemiologic evidence that high personal exposure to fine particles
      is associated with adverse effects on the developing fetus. These results
      indicate the need to reduce ambient fine particulate concentrations. However,
      further research should establish possible biologic mechanisms explaining the
      observed relationship.

PMID- 15471733
TI  - Paternal occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and birth
      outcomes of offspring: birth weight, preterm delivery, and birth defects.
AB  - Agent Orange is a phenoxy herbicide that was contaminated with 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). We studied pregnancy outcomes among wives of
      male chemical workers who were highly exposed to chemicals contaminated with TCDD
      and among wives of nonexposed neighborhood referents. For exposed pregnancies, we
      estimated serum TCDD concentration at the time of conception using a
      pharmacokinetic model. The mean TCDD concentration for workers' births was 254
      pg/g lipid (range, 3-16,340 pg/g). The mean referent concentration of 6 pg/g was
      assigned to pregnancies fathered by workers before exposure. A total of 1,117
      live singleton births of 217 referent wives and 176 worker wives were included.
      Only full-term births were included in the birth weight analysis (greater than or
      equal to 37 weeks of gestation). Mean birth weight among full-term babies was
      similar among referents' babies (n = 604), preexposure workers' babies (n = 221),
      and exposed workers' babies (n = 292) (3,420, 3,347, and 3,442 g, respectively).
      Neither continuous nor categorical TCDD concentration had an effect on birth
      weight for term infants after adjustment for infant sex, mother's education,
      parity, prenatal cigarette smoking, and gestation length. An analysis to estimate
      potential direct exposure of the wives during periods of workers' exposure
      yielded a nonstatistically significant increase in infant birth weight of 130 g
      in the highest exposure group (TCDD concentration > 254 pg/g) compared with
      referents (p = 0.09). Mothers' reports of preterm delivery showed a somewhat
      protective association with paternal TCDD (log) concentration (odds ratio = 0.8;
      95% confidence interval, 0.6-1.1). We also include descriptive information on
      reported birth defects. Because the estimated TCDD concentrations in this
      population were much higher than in other studies, the results indicate that TCDD
      is unlikely to increase the risk of low birth weight or preterm delivery through
      a paternal mechanism. Key words: birth defects, birth weight, congenital
      anomalies, dioxin, occupation, paternal exposure, preterm birth, TCDD.

PMID- 15471734
TI  - National environmental public health tracking program: bridging the information
      gap.
AB  - In January 2001 the Pew Environmental Health Commission called for the creation
      of a coordinated public health system to prevent disease in the United States by
      tracking and combating environmental health threats. In response, the Centers for
      Disease Control and Prevention initiated the Environmental Public Health Tracking
      (EPHT) Program to integrate three distinct components of hazard monitoring and
      exposure and health effects surveillance into a cohesive tracking network.
      Uniform and acceptable data standards, easily understood case definitions, and
      improved communication between health and environmental agencies are just a few
      of the challenges that must be addressed for this network to be effective. The
      nascent EPHT program is attempting to respond to these challenges by drawing on a
      wide range of expertise from federal agencies, state health and environmental
      agencies, nongovernmental organizations, and the program's academic Centers of
      Excellence. In this mini-monograph, we present innovative strategies and methods
      that are being applied to the broad scope of important and complex environmental
      public health problems by developing EPHT programs. The data resulting from this
      program can be used to identify areas and populations most likely to be affected
      by environmental contamination and to provide important information on the health
      and environmental status of communities. EPHT will develop valuable data on
      possible associations between the environment and the risk of noninfectious
      health effects. These data can be used to reduce the burden of adverse health
      effects on the American public.

PMID- 15471735
TI  - Identifying priority health conditions, environmental data, and infrastructure
      needs: a synopsis of the Pew Environmental Health tracking project.
AB  - In this article we describe the methodologic approaches of the Pew Environmental
      Health Commission at the Johns Hopkins Bloomberg School of Public Health used to
      identify priority environmental health conditions and develop recommendations to
      establish a national environmental public health tracking network. We present the
      results of a survey of public health and environmental practitioners to uncover
      state and local health tracking needs and priorities. We describe the steps that
      combined the findings from the state and local health tracking survey and a
      review of the state of the science on environmental impacts on health to identify
      priority health end points. Through an examination of national health and health
      care databases, we then describe trends and public health effects of those
      diseases that may be linked to the environment. Based on this analysis,
      respiratory diseases and neurologic diseases are recommended as priorities for
      tracking. Specific end points recommended for tracking include asthma and chronic
      respiratory diseases, and chronic neurodegenerative diseases such as multiple
      sclerosis. Based on trends in reported prevalence, consideration should also be
      given to developmental disabilities, reproductive disorders, and
      endocrine/metabolic disorders. Strengthening of current efforts to track cancer
      and birth defects should also be included as components of a nationwide health
      tracking network. Finally, we present the recommendations for environmental
      public health tracking. These recommendations provided the groundwork for the
      development of the Centers for Disease Control and Prevention's National
      Environmental Public Health Tracking Progam that now includes 21 states, three
      cities, and three academic centers throughout the nation.

PMID- 15471736
TI  - Developing a comprehensive pesticide health effects tracking system for an urban
      setting: New York City's approach.
AB  - In recent years, there have been substantial investments and improvements in
      federal and state surveillance systems to track the health effects from pesticide
      exposure. These surveillance systems help to identify risk factors for
      occupational exposure to pesticides, patterns in poisonings, clusters of disease,
      and populations at risk of exposure from pesticide use. Data from pesticide use
      registries and recent epidemiologic evidence pointing to health risks from urban
      residential pesticide use make a strong case for understanding better the sale,
      application, and use of pesticides in cities. In this article, we describe plans
      for the development of a pesticide tracking system for New York City that will
      help to elucidate where and why pesticides are used, potential risks to varied
      populations, and the health consequences of their use. The results of an
      inventory of data sources are presented along with a description of their
      relevance to pesticide tracking. We also discuss practical, logistical, and
      methodologic difficulties of linking multiple secondary data sources with
      different levels of person, place, and time descriptors.

PMID- 15471737
TI  - Tracking pediatric asthma: the Massachusetts experience using school health
      records.
AB  - The Massachusetts Department of Public Health, in collaboration with the U.S.
      Centers for Disease Control and Prevention Environmental Public Health Tracking
      Program, initiated a 3-year statewide project for the routine surveillance of
      asthma in children using school health records as the primary data source. School
      district nurse leaders received electronic data reporting forms requesting the
      number of children with asthma by grade and gender for schools serving grades
      kindergarten (K) through 8. Verification efforts from an earlier community-level
      study comparing a select number of school health records with primary care
      provider records demonstrated a high level of agreement (i.e., > 95%). First-year
      surveillance targeted approximately one-half (n = 958 schools) of all
      Massachusetts's K-8 schools. About 78% of targeted school districts participated,
      and 70% of the targeted schools submitted complete asthma data. School nurse
      reported asthma prevalence was as high as 30.8% for schools, with a mean of 9.2%.
      School-based asthma surveillance has been demonstrated to be a reliable and cost
      effective method of tracking disease through use of an existing and enhanced
      reporting structure.

PMID- 15471738
TI  - Using the Behavioral Risk Factor Surveillance System (BRFSS) for exposure
      tracking: experiences from Washington State.
AB  - One of the goals of the National Environmental Public Health Tracking Network is
      to link environmental data with chronic disease data as a means of improving our
      understanding of the environmental determinants of disease. Such efforts will
      rely on the ongoing collection of population exposure information, and there are
      few systems in place to track population exposures. In many cases, exposures can
      be estimated by combining environmental contaminant data with data about human
      behaviors. The Behavioral Risk Factor Surveillance System (BRFSS) provides a good
      opportunity to implement tracking of exposure-related behaviors. Washington State
      has used the BRFSS to collection information on environmentally related
      knowledge, attitudes, and behaviors. In this article we present case studies of
      modules covering drinking water, perceptions of environmental risk, and radon
      awareness and testing. Data on exposure-related behaviors have been useful for
      population exposure assessments and program evaluation. Questions about knowledge
      and attitudes and perceptions of environmental issues were not as useful because
      they lacked sufficient detail from which to modify existing education efforts. In
      some cases these data had not been used at all, indicating that the need for the
      data had not been well established. National development efforts should focus on
      compiling existing questions and developing questions on topics that are a
      priority at the state and national levels to be included as core questions and
      optional modules in future BRFSS surveys.

PMID- 15471739
TI  - Wisconsin's environmental public health tracking network: information systems
      design for childhood cancer surveillance.
AB  - In this article we describe the development of an information system for
      environmental childhood cancer surveillance. The Wisconsin Cancer Registry
      annually receives more than 25,000 incident case reports. Approximately 269 cases
      per year involve children. Over time, there has been considerable community
      interest in understanding the role the environment plays as a cause of these
      cancer cases. Wisconsin's Public Health Information Network (WI-PHIN) is a robust
      web portal integrating both Health Alert Network and National Electronic Disease
      Surveillance System components. WI-PHIN is the information technology platform
      for all public health surveillance programs. Functions include the secure,
      automated exchange of cancer case data between public health-based and hospital
      based cancer registrars; web-based supplemental data entry for environmental
      exposure confirmation and hypothesis testing; automated data analysis,
      visualization, and exposure-outcome record linkage; directories of public health
      and clinical personnel for role-based access control of sensitive surveillance
      information; public health information dissemination and alerting; and
      information technology security and critical infrastructure protection. For
      hypothesis generation, cancer case data are sent electronically to WI-PHIN and
      populate the integrated data repository. Environmental data are linked and the
      exposure-disease relationships are explored using statistical tools for ecologic
      exposure risk assessment. For hypothesis testing, case-control interviews collect
      exposure histories, including parental employment and residential histories. This
      information technology approach can thus serve as the basis for building a
      comprehensive system to assess environmental cancer etiology.

PMID- 15471740
TI  - Statistical methods for linking health, exposure, and hazards.
AB  - The Environmental Public Health Tracking Network (EPHTN) proposes to link
      environmental hazards and exposures to health outcomes. Statistical methods used
      in case-control and cohort studies to link health outcomes to individual exposure
      estimates are well developed. However, reliable exposure estimates for many
      contaminants are not available at the individual level. In these cases,
      exposure/hazard data are often aggregated over a geographic area, and ecologic
      models are used to relate health outcome and exposure/hazard. Ecologic models are
      not without limitations in interpretation. EPHTN data are characteristic of much
      information currently being collected--they are multivariate, with many
      predictors and response variables, often aggregated over geographic regions
      (small and large) and correlated in space and/or time. The methods to model
      trends in space and time, handle correlation structures in the data, estimate
      effects, test hypotheses, and predict future outcomes are relatively new and
      without extensive application in environmental public health. In this article we
      outline a tiered approach to data analysis for EPHTN and review the use of
      standard methods for relating exposure/hazards, disease mapping and clustering
      techniques, Bayesian approaches, Markov chain Monte Carlo methods for estimation
      of posterior parameters, and geostatistical methods. The advantages and
      limitations of these methods are discussed.

PMID- 15471741
TI  - Cultural diversity and neuropsychology: an uneasy relationship in a time of
      change.

PMID- 15471742
TI  - Neuropsychological test use with Hispanic/Latino populations in the United
      States: Part II of a national survey.

PMID- 15471743
TI  - Racial and ethnic diversity among trainees and professionals in psychology and
      neuropsychology: needs, trends, and challenges.
AB  - The United States is rapidly becoming a more racially and ethnically diverse
      nation, bringing the challenge of ensuring that health care specialties,
      including neuropsychology, are representative of and competent to serve the needs
      of this population. Initiatives have been undertaken to increase minority
      representation in training for psychology and neuropsychology. However, tracking
      progress requires reliable race/ethnicity data collection and reporting. On the
      2002 American Psychological Association (APA) Directory Survey (APA Research
      Office, 2002), up to 42% of the APA membership and up to 25% of the Division 40
      membership did not specify race/ethnicity status. Within Division 40, data for
      members who did report race/ethnicity suggest that representation of Hispanic,
      Asian, Black/African American, and Native American members lags substantially
      behind that of White members. Improved methods for collecting information on
      race/ethnicity are needed to meet diversity objectives.

PMID- 15471744
TI  - Neuropsychological assessment of Asian Americans: demographic factors, cultural
      diversity, and practical guidelines.
AB  - Asian Americans belong to 1 of the most rapidly growing ethnic minority groups in
      the United States. Clinical neuropsychologists unfamiliar with Asian American
      peoples and cultures may not be able to perform an adequate evaluation with an
      individual of Asian descent because of lack of understanding of how cultural
      variables might affect the assessment. This article attempts to provide some
      basic knowledge and principles by which to guide neuropsychologists who might
      work with an Asian American patient by (a) familiarizing the reader with basic
      information and descriptions of some of the major specific Asian subgroups, (b)
      providing a context within which neuropsychological test selection and
      interpretation can be adjusted to account for cultural and linguistic factors,
      and (c) providing practical suggestions for working with Asian American clients
      in a neuropsychological setting.

PMID- 15471745
TI  - Acculturation, reading level, and neuropsychological test performance among
      African American elders.
AB  - The independent effects of cultural and educational experience on
      neuropsychological test performance were examined among 503 nondemented African
      Americans ages 65 and older. Measures of cultural experience (acculturation) and
      quality of education (reading level) were administered. Reading level was the
      most influential predictor of cognitive test performance, even after accounting
      for age, sex, years of education, and acculturation level. Age had small but
      significant unique effects on most measures, especially word list learning. Years
      of education had independent effects on measures of verbal abstraction, fluency,
      and figure matching. More acculturated African Americans obtained higher scores
      on most measures; however, after accounting for age, years of education, sex, and
      reading level, the effect of acculturation was diminished. The results suggest
      that quality of education and cultural experience influence how older African
      Americans approach neuropsychological tasks; therefore, adjustment for these
      variables may improve specificity of neuropsychological measures.

PMID- 15471746
TI  - Differences in neuropsychological performance associated with ethnicity in
      children with HIV-1 infection: preliminary findings.
AB  - This study investigated the relationship between ethnicity (African American and
      European American) and neuropsychological performance in two specific
      neuropsychological domains (language and speed of information processing) in a
      group of HIV-1+ children. The Expressive One-Word Picture Vocabulary Test-Revised
      and the Rapid Color Naming subtest of the Comprehensive Test of Phonological
      Processing were administered to 5- to 7-year-old children (n = 22) as part of a
      comprehensive research or clinical protocol. African American children scored
      lower than European American children (p < .05) on both procedures. The observed
      performance difference emerged despite the fact that there were no group
      differences in age, immunologic clinical categories, intellect, level of maternal
      education, or CD4+ percentage and after using stringent exclusionary criteria,
      including history of enrollment in special education services and the presence of
      other chronic medical conditions. The implications of such findings are discussed
      within biological and demographic frameworks.

PMID- 15471747
TI  - Perception of health and quality of life in minorities after mild-to-moderate
      traumatic brain injury.
AB  - Much has been reported of the influence of age, affective symptoms, and
      satisfaction on self-ratings of health functioning, but little is known about the
      extent that race-based perceptions may have on influencing behavior or adjustment
      after a mild-to-moderate traumatic brain injury (MTBI). We investigated
      differences in perception of health functioning by race for mental and physical
      functioning using a global measure of health functioning. MTBI (n = 135) and
      general trauma (GT, n = 83) patients recruited from an area Level-1 trauma center
      at 3 months after injury were administered the Medical Outcomes Study: Short Form
      (SF-36), Structured Clinical Interview for the Diagnostic and Statistical Manual
      of Mental Disorders (4th ed.; American Psychiatric Association, 1994), Community
      Integration Questionnaire, Social Support Questionnaire (SSQ), Center for
      Epidemiological Studies-Depression, and the Visual Analogue Scale of Depression.
      A significant interaction for Race Group (p < .01) was found on the Physical
      Component Scale (PCS) of the SF-36. In the MTBI group, African Americans reported
      worse functioning (p < .04) on the PCS scale; they perceived functioning on
      subscales General Health Perception (p < .02) and Physical Functioning (p < .04)
      to be more limited. On the SSQ, Hispanic MTBI patients reported having fewer
      social supports available to them (p < .05), although the race groups were
      comparable for satisfaction with their support. Rate of depression across groups
      was comparable, although subjective reporting by minority MTBI patients indicated
      greater depressed feelings. Differences in perception of health functioning may
      be related to the unique interaction created between sustaining an MTBI and
      variations in cultural expression of disability. Manifestations of physical
      difficulties may be better accepted for some cultures than having mental illness.

PMID- 15471748
TI  - The interdisciplinary eHealth team: chronic care for the future.
AB  - An interdisciplinary clinical team is a consistent grouping of people from
      relevant clinical disciplines, ideally inclusive of the patient, whose
      interactions are guided by specific team functions and processes to achieve team
      defined favorable patient outcomes. Teamwork supported by properly designed
      eHealth applications could help create more effective systems of care for chronic
      disease. Given its synchronous and asynchronous communication capacity and
      information-gathering and -sharing capabilities, the Internet is a logical
      platform for supporting interdisciplinary clinical teamwork. Research is needed
      to better understand how interdisciplinary eHealth team members can work together
      in everyday practice and to guide the development of effective and efficient
      eHealth software applications to support greater clinical teamwork.

PMID- 15471749
TI  - Quantitative and qualitative usage data of an Internet-based asthma monitoring
      tool.
AB  - BACKGROUND: In May 2000, AstraZeneca launched a Web service for asthma patients
      and health-care providers called LinkMedica, which includes an asthma diary for
      monitoring and self-management. In the diary, the patient enters his or her peak
      flow, number of doses of rescue medication, and if there have been any asthma
      symptoms during the previous 24 hours. The patient receives an immediate response
      from LinkMedica, telling him or her if the asthma is under control and what to do
      if not, eg, increase the dose of inhaled steroid. Health-care providers have
      access to the patient diary. OBJECTIVES: The primary objective of the study was
      to describe patients' and health-care providers' use of LinkMedica. Secondary
      objectives were to evaluate their perception of the system and how the users'
      interaction with the system is influenced by their everyday lives. METHODS: Site
      statistics regarding number of registered users and diary usage were analyzed. An
      online survey among users (85 respondents), a mailed questionnaire to health-care
      providers (131 respondents; response rate 26.8%), as well as in-depth interviews
      with 10 patients and 5 general practitioners, elicited further quantitative and
      qualitative data on users' perceptions. RESULTS: In February 2003, a total of
      7653 users had registered. During 2002, the growth in registered users averaged
      50 per month. In the same period, the number of unique diary users per month
      decreased from 307 to 138. Patients usually stopped using the diary after a short
      time; the doctors were reluctant to introduce the diary to patients because of
      time constraints. Several user subtypes were identified among patients and their
      relatives. CONCLUSION: The self-selected survey responses and in-depth interviews
      indicated that LinkMedica is generally considered a trustworthy and reliable site
      by both patients and doctors. However, there was a contrast between users'
      positive perception of LinkMedica and their unwillingness to use the site for
      more than short periods. The primary reason for this was that LinkMedica did not
      fit into their everyday lives because of technical and psychological aspects. A
      number of recommendations to improve LinkMedica are suggested.

PMID- 15471750
TI  - The effect of top-level domains and advertisements on health web-site
      credibility.
AB  - BACKGROUND: Concerns over health information on the Internet have generated
      efforts to enhance credibility markers; yet how users actually assess the
      credibility of online health information is largely unknown. OBJECTIVE: This
      study set out to (1) establish a parsimonious and valid questionnaire instrument
      to measure credibility of Internet health information by drawing on various
      previous measures of source, news, and other credibility scales; and (2) to
      identify the effects of Web-site domains and advertising on credibility
      perceptions. METHODS: Respondents (N = 156) examined one of 12 Web-site mock-ups
      and completed credibility scales in a 3 x 2 x 2 between-subjects experimental
      design. Factor analysis and validity checks were used for item reduction, and
      analysis of variance was employed for hypothesis testing of Web-site features'
      effects. RESULTS: In an attempt to construct a credibility instrument, three
      dimensions of credibility (safety, trustworthiness, and dynamism) were retained,
      reflecting traditional credibility sub-themes, but composed of items from
      disparate sources. When testing the effect of the presence or absence of
      advertising on a Web site on credibility, we found that this depends on the
      site's domain, with a trend for advertisements having deleterious effects on the
      credibility of sites with .org domain, but positive effects on sites with .com or
      .edu domains. CONCLUSIONS: Health-information Web-site providers should select
      domains purposefully when they can, especially if they must accept on-site
      advertising. Credibility perceptions may not be invariant or stable, but rather
      are sensitive to topic and context. Future research may employ these findings in
      order to compare other forms of health-information delivery to optimal Web-site
      features.

PMID- 15471751
TI  - Internet usage by low-literacy adults seeking health information: an
      observational analysis.
AB  - BACKGROUND: Adults with low literacy may encounter informational obstacles on the
      Internet when searching for health information, in part because most health Web
      sites require at least a high-school reading proficiency for optimal access.
      OBJECTIVE: The purpose of this study was to 1) determine how low-literacy adults
      independently access and evaluate health information on the Internet, 2) identify
      challenges and areas of proficiency in the Internet-searching skills of low
      literacy adults. METHODS: Subjects (n=8) were enrolled in a reading assistance
      program at Bidwell Training Center in Pittsburgh, PA, and read at a 3rd to 8th
      grade level. Subjects conducted self-directed Internet searches for designated
      health topics while utilizing a think-aloud protocol. Subjects' keystrokes and
      comments were recorded using Camtasia Studio screen-capture software. The search
      terms used to find health information, the amount of time spent on each Web site,
      the number of Web sites accessed, the reading level of Web sites accessed, and
      the responses of subjects to questionnaires were assessed. RESULTS: Subjects
      collectively answered 8 out of 24 questions correctly. Seven out of 8 subjects
      selected "sponsored sites"-paid Web advertisements-over search engine-generated
      links when answering health questions. On average, subjects accessed health Web
      sites written at or above a 10th grade reading level. Standard methodologies used
      for measuring health literacy and for promoting subjects to verbalize responses
      to Web-site form and content had limited utility in this population. CONCLUSION:
      This study demonstrates that Web health information requires a reading level that
      prohibits optimal access by some low-literacy adults. These results highlight the
      low-literacy adult population as a potential audience for Web health information,
      and indicate some areas of difficulty that these individuals face when using the
      Internet and health Web sites to find information on specific health topics.

PMID- 15471752
TI  - Online health information and low-literacy African Americans.
AB  - African Americans with low incomes and low literacy levels disproportionately
      suffer poor health outcomes from many preventable diseases. Low functional
      literacy and low health literacy impede millions of Americans from successfully
      accessing health information. These problems are compounded for African Americans
      by cultural insensitivity in health materials. The Internet could become a useful
      tool for providing accessible health information to low-literacy and low-income
      African Americans. Optimal health Web sites should include text written at low
      reading levels and appropriate cultural references. More research is needed to
      determine how African Americans with low literacy skills access, evaluate,
      prioritize, and value health information on the Internet.

PMID- 15471753
TI  - Reformulation of consumer health queries with professional terminology: a pilot
      study.
AB  - BACKGROUND: The Internet is becoming an increasingly important resource for
      health-information seekers. However, consumers often do not use effective search
      strategies. Query reformulation is one potential intervention to improve the
      effectiveness of consumer searches. OBJECTIVE: We endeavored to answer the
      research question: "Does reformulating original consumer queries with preferred
      terminology from the Unified Medical Language System (UMLS) Metathesaurus lead to
      better search returns?" METHODS: Consumer-generated queries with known goals
      (n=16) that could be mapped to UMLS Metathesaurus terminology were used as test
      samples. Reformulated queries were generated by replacing user terms with
      Metathesaurus-preferred synonyms (n=18). Searches (n=36) were performed using
      both a consumer information site and a general search engine. Top 30 precision
      was used as a performance indicator to compare the performance of the original
      and reformulated queries. RESULTS: Forty-two percent of the searches utilizing
      reformulated queries yielded better search returns than their associated original
      queries, 19% yielded worse results, and the results for the remaining 39% did not
      change. We identified ambiguous lay terms, expansion of acronyms, and arcane
      professional terms as causes for changes in performance. CONCLUSIONS: We noted a
      trend towards increased precision when providing substitutions for lay terms,
      abbreviations, and acronyms. We have found qualitative evidence that
      reformulating queries with professional terminology may be a promising strategy
      to improve consumer health-information searches, although we caution that
      automated reformulation could in fact worsen search performance when the
      terminology is ill-fitted or arcane.

PMID- 15471754
TI  - Using the internet for life style changes in diet and physical activity: a
      feasibility study.
AB  - BACKGROUND: LinkMedica-Heart is a novel Internet based program intended to
      support people who seek to improve their life style by means of changes in diet
      and physical activity. The program is currently under evaluation in a clinical
      study and the present study is a feasibility test of the LinkMedica-Heart
      Internet based program. OBJECTIVE: The aim of this study was to evaluate
      LinkMedica-Heart, an Internet based program we designed for support and
      maintenance of patient-led life style changes. METHODS: The feasibility study of
      LinkMedica-Heart presented here is a qualitative study. Nine general
      practitioners were invited to participate. Each practitioner was asked to
      introduce LinkMedica-Heart to not less than two patients, with a maximum of five
      patients per practitioner. Patients and general practitioners were both asked to
      participate in testing the program for a period of 6 months. At the end of 6
      months, evaluation meetings were held with the general practitioners, and
      separate interviews took place with some of the participating patients who were
      selected by the GPs. RESULTS: Five general practitioners and 25 patients
      participated in the study. The general practitioners and the patients were
      enthusiastic about the prospect of an Internet based life style change program.
      However, the program was not able to sustain patient loyalty over an extended
      period. The doctors found that the program was much too complicated to navigate
      and that the results from the program could not be trusted. The patients in
      contrast had fewer complaints about the program design, but found that the advice
      given by the program was too elaborate and detailed and, in general, did not add
      to the patient's knowledge on life style change. CONCLUSION: Our study confirms
      that there is a need for, and a receptive attitude toward a Web-based program
      that supports people who want to improve their life style and health. LinkMedica
      Heart in its present form does not satisfy these needs. We suggest a number of
      design changes and improvements to the program.

PMID- 15471755
TI  - Internet versus mailed questionnaires: a randomized comparison.
AB  - BACKGROUND: The use of Internet-based questionnaires for collection of data to
      evaluate patient education and other interventions has increased in recent years.
      Many self-report instruments have been validated using paper-and-pencil versions,
      but we cannot assume that the psychometric properties of an Internet-based
      version will be identical. OBJECTIVES: To look at similarities and differences
      between the Internet versions and the paper-and-pencil versions of 16 existing
      self-report instruments useful in evaluation of patient interventions. METHODS:
      Participants were recruited via the Internet and volunteered to participate
      (N=397), after which they were randomly assigned to fill out questionnaires
      online or via mailed paper-and-pencil versions. The self-report instruments
      measured were overall health, health distress, practice mental stress management,
      Health Assessment Questionnaire (HAQ) disability, illness intrusiveness, activity
      limitations, visual numeric for pain, visual numeric for shortness of breath,
      visual numeric for fatigue, self-efficacy for managing disease, aerobic exercise,
      stretching and strengthening exercise, visits to MD, hospitalizations, hospital
      days, and emergency room visits. Means, ranges, and confidence intervals are
      given for each instrument within each type of questionnaire. The results from the
      two questionnaires were compared using both parametric and non-parametric tests.
      Reliability tests were given for multi-item instruments. A separate sample (N=30)
      filled out identical questionnaires over the Internet within a few days and
      correlations were used to assess test-retest reliability. RESULTS: Out of 16
      instruments, none showed significant differences when the appropriate tests were
      used. Construct reliability was similar within each type of questionnaire, and
      Internet test-retest reliability was high. Internet questionnaires required less
      follow-up to achieve a slightly (non-significant) higher completion rate compared
      to mailed questionnaires. CONCLUSIONS: Among a convenience sample recruited via
      the Internet, results from those randomly assigned to Internet participation were
      at least as good as, if not better than, among those assigned mailed
      questionnaires, with less recruitment effort required. The instruments
      administered via the Internet appear to be reliable, and to be answered similarly
      to the way they are answered when they are administered via traditional mailed
      paper questionnaires.

PMID- 15471757
TI  - Will web surveys ever become part of mainstream research?

PMID- 15471756
TI  - Internet versus mailed questionnaires: a randomized comparison (2).
AB  - BACKGROUND: Low response rates among surgeons can threaten the validity of
      surveys. Internet technologies may reduce the time, effort, and financial
      resources needed to conduct surveys. OBJECTIVE: We investigated whether using Web
      based technology could increase the response rates to an international survey.
      METHODS: We solicited opinions from the 442 surgeon-members of the Orthopaedic
      Trauma Association regarding the treatment of femoral neck fractures. We
      developed a self-administered questionnaire after conducting a literature review,
      focus groups, and key informant interviews, for which we used sampling to
      redundancy techniques. We administered an Internet version of the questionnaire
      on a Web site, as well as a paper version, which looked similar to the Internet
      version and which had identical content. Only those in our sample could access
      the Web site. We alternately assigned the participants to receive the survey by
      mail (n=221) or an email invitation to participate on the Internet (n=221). Non
      respondents in the mail arm received up to three additional copies of the survey,
      while non-respondents in the Internet arm received up to three additional
      requests, including a final mailed copy. All participants in the Internet arm had
      an opportunity to request an emailed Portable Document Format (PDF) version.
      RESULTS: The Internet arm demonstrated a lower response rate (99/221, 45%) than
      the mail questionnaire arm (129/221, 58%) (absolute difference 13%, 95%
      confidence interval 4%-22%, P<0.01). CONCLUSIONS: Our Internet-based survey to
      surgeons resulted in a significantly lower response rate than a traditional
      mailed survey. Researchers should not assume that the widespread availability and
      potential ease of Internet-based surveys will translate into higher response
      rates.

PMID- 15471758
TI  - HIV-positive youth's perspectives on the Internet and e-health.
AB  - BACKGROUND: Globally, half of all new HIV infections occur among young people.
      Despite this incidence, there is a profound lack of resources for HIV-positive
      youth. OBJECTIVE: To investigate Internet access, use and acceptability as means
      for health promotion and health service delivery among HIV-positive youth.
      METHODS: A community-based participatory approach was used to conduct a mixed
      methods research study. Thirty-five qualitative in-depth semi-structured
      interviews were conducted with youth (ages 12-24) living with HIV in Ontario.
      Also, brief structured demographic surveys were administered at the time of the
      interview. A stakeholder group of youth living with HIV, professionals and
      researchers collaboratively analyzed the data for emerging themes. RESULTS: Five
      main themes were identified with respect to the youth's use of and interest in
      the Internet as a health promotion strategy. These include: (1) high rates of
      Internet use and access; (2) issues around public and private terminals; (3)
      their use of the Internet primarily for communication and entertainment; (4) the
      rarity of health information seeking behavior in this group; and (5) wanting "one
      stop shopping" from an e-health site. HIV-positive youth were enthusiastic about
      the possibility of content that was developed specifically to target them and
      their needs. Also, they were keen about the possibilities for increased social
      support that youth-specific online chat rooms and message boards might provide.
      CONCLUSION: Given high rates of use, access and interest, the Internet provides
      an important way to reach young people living with HIV using health services and
      health promotion programs. The onus is on e-Health developers to understand the
      particular needs of HIV-positive youth and create relevant content.

PMID- 15471759
TI  - Disease management and the Internet.

PMID- 15471760
TI  - Improving the quality of Web surveys: the Checklist for Reporting Results of
      Internet E-Surveys (CHERRIES).
AB  - Analogous to checklists of recommendations such as the CONSORT statement (for
      randomized trials), or the QUORUM statement (for systematic reviews), which are
      designed to ensure the quality of reports in the medical literature, a checklist
      of recommendations for authors is being presented by the Journal of Medical
      Internet Research (JMIR) in an effort to ensure complete descriptions of Web
      based surveys. Papers on Web-based surveys reported according to the CHERRIES
      statement will give readers a better understanding of the sample (self-)selection
      and its possible differences from a "representative" sample. It is hoped that
      author adherence to the checklist will increase the usefulness of such reports.

PMID- 15471761
TI  - Tackling publication bias and selective reporting in health informatics research:
      register your eHealth trials in the International eHealth Studies Registry.
AB  - Beginning in July 2005, several major medical journals, including the Journal of
      Medical Internet Research, will only consider trials for publication that have
      been registered in a trial registry before they started. This is to reduce
      publication bias and to prevent selective reporting of positive outcomes. As
      existing clinical trial registers seem to be unsuitable or suboptimal for eHealth
      studies, a free International eHealth Study Registry (IESR) has been set up,
      allowing registration of trials (including non-randomized studies) in the field
      of health informatics and assigning an International eHealth Study Number (IESN).
      The IESR should meet the requirements of journal editors for a-priori
      registration of a study. We hope IESR will become the preferred choice for
      registration of eHealth studies and, as an secondary benefit, will become an
      international repository of ongoing eHealth projects, thereby enhancing global
      collaboration and reducing duplication of effort.

PMID- 15471762
TI  - The role of the Internet in patient-practitioner relationships: findings from a
      qualitative research study.
AB  - BACKGROUND: Studies suggest that there has been an increase in the use of the
      Internet by patients in many Western societies. However, despite the many texts
      available on health and the Internet, not much is known about how much patients
      actually use the Internet to look up health information in their daily lives. We
      know little about what meaning this activity has for their experience of health
      and illness, and for their relationship with health-care practitioners.
      OBJECTIVE: To explore patients' and practitioners' use of the Internet and to
      consider whether use of the Internet is changing relationships between patients
      and health-care practitioners. METHOD: The study used qualitative interviews and
      observations of patient-practitioner interaction. Our purposive sample of 47
      patients (32 women and 15 men) had all had contact with the health services for
      information/treatment in relation to hormone replacement therapy (HRT)/menopause
      and Viagra/erectile dysfunction. The setting for the research was in general
      practitioners' surgeries, specialist clinics and patients' homes in the United
      Kingdom. Participants reflected a wide range of socio-economic groups, but most
      were white and British born, which, given the ethnic make-up of the town in which
      we conducted the research, was not surprising. In addition to patients, we
      interviewed 10 health-care practitioners (4 consultant doctors, 3 GPs, 2
      specialist nurses, and a psychologist) about their own health information seeking
      practices (HISPs) and those of their patients. RESULTS: Use of the Internet can
      increase patients' knowledge about their health conditions, although patients in
      our study were often too overwhelmed by the information available on the Internet
      to make an informed decision about their own care. Patients have a great deal of
      trust in their health-care practitioners. Health-care practitioners need to
      improve their own skills in Internet use. Hype around Internet use by patients
      appears to exceed the reality of Internet use. CONCLUSIONS: Our qualitative study
      suggests that use of the Internet is contributing to subtle changes in the
      relationship between health-care practitioners and their patients, rather than
      effecting the dramatic transformation some people envisage for it.

PMID- 15471763
TI  - Peer-review and publication of research protocols and proposals: a role for open
      access journals.
AB  - Peer-review and publication of research protocols offer several advantages to all
      parties involved. Among these are the following opportunities for authors:
      external expert opinion on the methods, demonstration to funding agencies of
      prior expert review of the protocol, proof of priority of ideas and methods, and
      solicitation of potential collaborators. We think that review and publication of
      protocols is an important role for Open Access journals. Because of their
      electronic form, openness for readers, and author-pays business model, they are
      better suited than traditional journals to ensure the sustainability and quality
      of protocol reviews and publications. In this editorial, we describe the workflow
      for investigators in eHealth research, from protocol submission to a funding
      agency, to protocol review and (optionally) publication at JMIR, to registration
      of trials at the International eHealth Study Registry (IESR), and to publication
      of the report. One innovation at JMIR is that protocol peer reviewers will be
      paid a honorarium, which will be drawn partly from a new submission fee for
      protocol reviews. Separating the article processing fee into a submission and a
      publishing fee will allow authors to opt for "peer-review only" (without
      subsequent publication) at reduced costs, if they wish to await a funding
      decision or for other reasons decide not to make the protocol public.

PMID- 15471764
TI  - Vitamin D-interacting protein 205 (DRIP205) coactivation of estrogen receptor
      alpha (ERalpha) involves multiple domains of both proteins.
AB  - Vitamin D-interacting protein 205 (DRIP205) is a mediator complex protein that
      anchors the complex to the estrogen receptor (ER) and other nuclear receptors
      (NRs). In ZR-75 breast cancer cells treated with 17beta-estradiol (E2) and
      transfected with a construct containing three tandem estrogen responsive elements
      (pERE(3)), DRIP205 coactivates ERalpha-mediated transactivation. DRIP205Delta587
      636 is a DRIP205 mutant in which both NR boxes within amino acids 587-636 have
      been deleted and, in parallel transfection studies, DRIP205Delta587-636 also
      coactivates ERalpha. Moreover, both wild-type and variant DRIP205 also colocalize
      with ERalpha in the nuclei of transfected cells. Extensive deletion analysis of
      DRIP205 shows that multiple domains of this protein play a role in coactivation
      of ERalpha and in interactions with ERalpha. Coactivation of ERalpha by DRIP205
      does not require NR boxes, and variants with deletion of N-terminal (amino acids
      1-639) and C-terminal (amino acids 576-1566) significantly coactivate ERalpha.
      DRIP205 resembles p160 coactivators that also interact with multiple regions of
      ERalpha; however, unlike p160 coactivators, DRIP205 coactivation of ERalpha does
      not require NR boxes.

PMID- 15471765
TI  - Effects of generic-only drug coverage in a Medicare HMO.
AB  - Rising pharmacy costs and demand for prescription drug coverage for broader
      populations of seniors have resulted in the implementation of generic-only
      pharmacy benefits in Medicare health maintenance organizations (HMOs). The impact
      on cost and quality of care is unknown. We examined data for members of a
      California Medicare HMO whose coverage changed to a generic-only benefit and
      found that the change was associated with reduced health plan pharmacy cost,
      increased out-of-pocket pharmacy costs for members, increased overall hospital
      admissions, changed drug-use patterns, and a negative impact on quality metrics
      for certain conditions. These findings have important implications for future
      research and health policy decisions.

PMID- 15471766
TI  - Lumpers and splitters: different approaches to understanding variations research.
AB  - The latest work of John Wennberg and colleagues represents an important advance
      over earlier work by targeting different domains of clinical care at a more
      specific level. The findings have clear implications for those interested in
      constraining Medicare costs and may even point a way forward for lasting reform
      of purchasing practices in both the public and the private sectors. Nonetheless,
      the latest findings and proposals leave unresolved important research and policy
      questions, including those involving the basic relationship between spending and
      outcomes and payment reforms that would promote care of more uniform quality.

PMID- 15471767
TI  - Twenty-year trends in regional variations in the U.S. physician workforce.
AB  - Large differences in the regional supply of physicians have challenged
      traditional methods of determining the "right" workforce rate. With continued
      growth expected in the number of U.S. physicians per capita, this study examines
      changes in regional variation over time to provide perspective on where future
      physicians are likely to locate. There was a slight reduction in workforce
      variation during the past twenty years as the aggregate supply per capita grew
      more than 50 percent. Most physicians located in regions with an already large
      supply. Given these persistent patterns, the population benefits of further
      growth in the physician workforce are uncertain.

PMID- 15471768
TI  - Trends and geographic variations in major surgery for degenerative diseases of
      the hip, knee, and spine.
AB  - Although Medicare rates for surgery to treat degenerative diseases of the hip,
      knee, and spine are highly variable among hospital referral regions (HRRs), the
      relative risk for surgery within a region is constant from year to year-a large
      majority of the variation in surgery in 2000--01 is "explained" by the variation
      in rates in 1992--93. The within-region constancy in rates for highly variable
      procedures (the "surgical signature") is illustrated for South Florida HRRs.
      Involving the patient in choice of treatments (shared decision making) and
      outcomes research are promising strategies for reducing unwarranted regional
      variation and local constancy in surgery risk.

PMID- 15471769
TI  - Wrestling with variation: an interview with Jack Wennberg [interviewed by
      Fitzhugh Mullan].
AB  - For thirty years Jack Wennberg has studied variations in medical practice, from
      rates of tonsillectomy in Vermont villages in the 1970s to the cost of dying in
      the nation's major medical centers today. Along the way he has spawned the field
      of clinical evaluative science, created the Dartmouth Atlas of Health Care,
      stimulated the creation of a new federal agency (the Agency for Healthcare
      Research and Quality), and challenged many presumptions about what constitutes
      good medical care. In this interview with Fitzhugh Mullan, he reflects on health
      care reform and how to change clinical practice.

PMID- 15471770
TI  - Modifying unwarranted variations in health care: shared decision making using
      patient decision aids.
AB  - Shared decision making is the process of interacting with patients in arriving at
      informed values-based choices when options have features that patients value
      differently. Patient decision aids (PtDAs) are evidence-based tools designed to
      facilitate that process. Numerous randomized trials indicate that PtDAs improve
      decision quality and prevent overuse of options that informed patients do not
      value. Therefore, they have a potential role in reducing unwarranted variations
      in the use of preference-sensitive health care options. However, barriers to
      their widespread use need to be addressed with coherent plans for ensuring good
      standards, improving access to PtDAs, training practitioners, testing practice
      models, and launching demonstration projects.

PMID- 15471771
TI  - Use of Medicare claims data to monitor provider-specific performance among
      patients with severe chronic illness.
AB  - This study illustrates that Medicare claims can be used to measure population
      based, provider-specific rates of resource inputs, utilization, and Medicare
      spending. The target populations are seventy-seven cohorts of chronically ill
      Medicare enrollees who received most of their care from seventy-seven well-known
      U.S. hospitals. Striking variations are documented in resource inputs and use of
      services during the last six months of life. The patterns of care seen in the
      progression of chronic illness correlate highly with care received during
      previous periods. We believe that hospital-specific measures can be helpful in
      identifying providers with acceptable quality indices who are also relatively
      efficient in managing chronic illness.

PMID- 15471772
TI  - Policy support for patient-centered care: the need for measurable improvements in
      decision quality.
AB  - The phenomenon of practice variation draws attention to the need for better
      management of clinical decision making as a means of ensuring quality. Different
      policies to address variations, including guidelines and measures of
      appropriateness, have had little demonstrable impact on variation itself or on
      the underlying quality problems. Variations in rates of interventions raise
      questions about the patient-centeredness of decisions that determine what care is
      provided to whom. Policies that support the development and routine use of
      measures of decision quality will provide opportunities to measurably improve the
      quality of decisions, thereby leading to more patient-centered and efficient
      health care.

PMID- 15471773
TI  - Regional availability of high-volume hospitals for major surgery.
AB  - Despite evidence of increased risks, a large number of patients still have
      surgery in low-volume hospitals. To better understand why, we used Medicare data
      to study the regional availability of high-volume hospitals. More than half of
      patients undergoing three procedures in low-volume hospitals lived in regions
      lacking a high-volume hospital. Some regions simply lacked enough cases to
      support a high-volume hospital. Other regions had enough cases but too many
      hospitals performing them. Although consolidation of surgical services may be
      feasible in some settings, volume-based referral strategies are impractical for
      many U.S. regions.

PMID- 15471775
TI  - Who you are and where you live: how race and geography affect the treatment of
      medicare beneficiaries.
AB  - The existence of overall racial and ethnic disparities in health care is well
      documented, but this average effect masks variation across regions and types of
      care. Medicare claims data are used to document the extent of these variations.
      Regions with high racial disparities in one procedure are not more likely to be
      high in other procedures. Unusually large racial disparities in surgery are often
      the result of high white rates rather than low black rates. Differences in end-of
      life care are driven more by residence than by race. Policies should focus on
      getting the rates right, rather than solely on racial differences.

PMID- 15471777
TI  - Variations in the longitudinal efficiency of academic medical centers.
AB  - Recent studies have revealed dramatic differences among academic medical centers
      (AMCs) in the quantity of care provided to their patients. The implications,
      however, depend upon whether the additional resources provided by some centers
      lead to better results. This study describes the content, quality, and outcomes
      of care across AMCs that differ by up to 60 percent in the overall intensity of
      medical services delivered to patients with serious chronic illnesses. Efforts to
      reduce costs will require attention to supply-sensitive services (the frequency
      of hospital stays, physician visits, specialist consultations, diagnostic tests,
      and minor procedures) and should include a focus on the longitudinal efficiency
      of hospitals and medical staffs.

PMID- 15471778
TI  - Practice variations and health care reform: connecting the dots.
AB  - Unwarranted variation is a ubiquitous feature of U.S. health care. Remedies for
      variations exist, and several are described in the current collection of Health
      Affairs papers. Several obstacles stand in the way of widespread adoption of
      these remedies: (1) a quality agenda that has yet to focus on improving the
      quality of patient decision making; (2) economic incentives that do not reward
      exemplary practice; and (3) the poor state of clinical science. Medicare reform
      legislation creates the opportunity for a demonstration project to redesign
      health care to address these barriers. We also must grapple with the cultural
      bias that more care is better and that physicians must know best.

PMID- 15471779
TI  - Quality as a system property: section 646 of the Medicare Modernization Act.
AB  - The Medicare Trustees' 2004 report indicates that the Part A Hospital Insurance
      trust fund will be exhausted by 2019. Medicare's sustainable growth rate (SGR)
      formula for physician reimbursement is widely recognized as being flawed; if it
      is not reformed, it may result in reduced access to physician services for
      beneficiaries. MedPAC proposes an alternative to the SGR formula that involves
      explicit consideration of Medicare program objectives and ensures that payments
      for physician services be adequate to maintain access. Section 646 of the
      Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003 may
      provide answers regarding providing high-quality care in fee-for-service
      Medicare.

PMID- 15471780
TI  - Moving toward a more patient-centered health care delivery system.
AB  - Quality-of-care measurement has not kept pace with the recent shift toward policy
      approaches that rely on patients to contain costs and improve quality. If
      patients are to play a critical role in care, then the degree to which providers
      support and improve patients' capabilities for participation must also be part of
      the quality measurement picture. Quality measures that focus on intermediate
      patient outcomes (such as self-management ability), that follow the patient over
      time, and that integrate measurement into the processes of care are necessary to
      move toward a delivery system that is centered on patients.

PMID- 15471781
TI  - Promoting the dissemination of decision aids: an odyssey in a dysfunctional
      health care financing system.
AB  - The usefulness of patient decision aids (PtDAs) is well documented, yet they are
      not in widespread use. Barriers include assuring balance and fairness (auspices
      matter), the cost of producing and maintaining them, and getting them into the
      hands of patients at the right time. The Foundation for Informed Medical Decision
      Making and its for-profit partner, Health Dialog, have developed a creative
      business model that helps overcome these barriers and has greatly expanded the
      reach of decision aids.

PMID- 15471782
TI  - Decisions, decisions: why the quality of medical decisions matters.
AB  - Questions about the process leading to particular medical decisions are seldom
      addressed in discussions of health care quality. In some cases, strict adherence
      to treatment protocols may overlook important elements in the clinical decision
      making process, such as physicians' judgment and patients' preferences. Papers by
      Annette O'Connor and colleagues and Karen Sepucha and colleagues are welcome
      additions to this debate because they highlight the importance of the medical
      decision-making process; they suggest that the quality of this process should be
      considered when evaluating health care quality. I explore some key limitations
      and uncertainties that must be addressed before work in this area can become
      broadly applicable.

PMID- 15471783
TI  - The Dartmouth data: moving from analysis to action.
AB  - The work of Jack Wennberg and colleagues on variations in medical practice and
      outcomes has clarified our understanding of the relationships between supply,
      costs, and quality of medical care. Variations persist, however, in spite of our
      knowledge of them. Progress in reducing these variations will require technical,
      political, and regulatory solutions to problems surrounding financial incentives
      and health care delivery. Wennberg's paper uses Medicare claims data to focus on
      specific providers rather than geographic regions. However, "real-time"
      availability of such data is necessary to maximize their usefulness, and
      collective action will be required to overcome obstacles to that goal.

PMID- 15471784
TI  - When excuses run dry: transforming the U.S. health care system.
AB  - Mainstream media have reported on the wide variation in clinical practice
      documented for years by health service researchers. Raising awareness of the
      quality and cost implications of clinical variation, however, is not enough to
      adopt clinical behavior based on the principles of evidence-based medicine (EBM).
      Preoccupation with EBM's limitations--which can be overcome--and failure to
      address its misperceptions inhibit transformation to an evidence-based system of
      care and payment. Three reinforcing efforts are needed: aligning payment with
      quality; increasing the engagement of consumers; and accelerating investment in
      and adoption of information technology. Real transformation in health care
      requires changes in both culture and attitudes.

PMID- 15471785
TI  - The problem of multiple margins.
AB  - The papers in this collection extend the work of John Wennberg and colleagues on
      variations in the use of health care services and the relationships between
      variations and health outcomes. Below I explore some theoretical issues that shed
      light on these observations and reconcile them with other findings in the
      literature that appear to contradict the work presented here. The analysis
      centers importantly on the distinction between different types of margins. It is
      important to understand these differences as a preparation to predicting the
      outcomes of possible health care reforms.

PMID- 15471786
TI  - Everything new is old again.
AB  - For more than thirty years, John Wennberg and his colleagues have been
      documenting variations in patterns of health care use from one community to the
      next, which are not explained by illness or demographic patterns. Twenty years
      ago Health Affairs devoted an issue to a symposium on this work, and it is
      striking how little some things have changed in the intervening years. In fact,
      there have been enormous changes in physicians' behavior and patterns of medical
      practice, but our cost problems seem as intractable as ever, perhaps because
      policymakers continue to focus erroneously on the relationship between use and
      costs.

PMID- 15471787
TI  - More variation in use of care, more flat-of-the-curve medicine.
AB  - Variation in use of health care is ubiquitous in the United States. It is
      attributable to exogenous differences in supply of medical resources; to
      identified and unidentified economic, social, and cultural factors; and to the
      idiosyncratic beliefs of physicians. It is perpetuated by the parochial character
      of much clinical practice. Patients in high-intensity areas do not appear to have
      better health outcomes: Much care is "flat of the curve." A more robust
      scientific foundation for clinical decisions could help to reduce variations, but
      major reform of health care financing is probably necessary to achieve
      substantial improvement in the organization and delivery of care.

PMID- 15471788
TI  - Cassida Award Winner Response: impact of modern technology on graduate education
      in animal sciences.

PMID- 15471790
TI  - The power of tests for bioequivalence in feed experiments with poultry.
AB  - Several studies have compared the feeding of genetically modified (GM) grains and
      conventional grains to poultry. The general conclusion has been that there were
      no significant differences detected in the biological performance of the birds
      (i.e., the grains were bioequivalent). However, the question has been posed
      whether the experimental designs used in the studies had sufficient statistical
      power to detect treatment differences. The power of tests can be used to
      determine the ability of an experimental design to detect treatment differences.
      The definition of statistical power is the probability of rejecting the null
      hypothesis when it is false and should be rejected. The complement of statistical
      power is the Type II error (beta). That is, accepting the null hypothesis that
      there is no difference in treatments when there is one. A priori power analysis
      can indicate the probability at which the sampling regimen or experiment can
      actually detect an effect if a difference exists. Post hoc power analysis
      indicates the sufficiency or the sample size needed for an experiment that has
      already been conducted. In the current study, the power of tests for experiments
      published in the literature where significant and nonsignificant differences were
      reported between control birds and birds fed new feed grains was examined. With
      some exceptions, the power of tests is rarely formally considered or mentioned in
      poultry research. The results of the survey of the literature showed, in general,
      low power of statistical tests for feeding experiments involving non-GM grains or
      in those cases when GM and non-GM grains were compared in poultry feeding
      experiments. These results suggest that care needs to be taken when designing
      experiments for bioequivalence of grains fed to poultry.

PMID- 15471789
TI  - Alteration of somatotropic function by proinflammatory cytokines.
AB  - Infections direct amino acids away from growth and skeletal muscle accretion
      toward the hepatic synthesis of acute-phase proteins. The loss of skeletal muscle
      protein stores results in both a decrease in muscle function and an increase in
      mortality. In general, muscle protein synthesis is decreased in rodent models of
      sepsis, as well as after the injection of components of the bacterial cell wall,
      such as lipopolysaccharide. Although the overexpression of proinflammatory
      cytokines is known to hasten the loss of skeletal muscle protein, it is not known
      whether this represents a direct effect of cytokines or results from secondary
      changes in the IGF system. Plasma concentrations of IGF-I are dramatically
      lowered by infection in rats, mice, pigs, and steers. The drop in IGF-I often
      occurs despite an increase in the plasma concentration of somatotropin. Animals
      are therefore considered to be GH resistant. The IGF bioactivity is determined
      not only by the plasma concentration of the ligand, but also by IGFBP; IGFBP-3 is
      the most abundant of these binding proteins and undergoes proteolysis during some
      catabolic states. In contrast to IGFBP-3, the plasma concentration of inhibitory
      IGFBP, such as IGFBP-1, is increased during infection. Insulin-like growth factor
      binding protein-1 accumulates in skeletal muscle, where it can potentially
      inhibit IGF-dependent protein synthesis. Insulin-like growth factor-I and IGFBP-1
      are regulated at the level of gene transcription by proinflammatory cytokines.
      Recent studies demonstrate that bacterial components that activate immune cells
      also activate the innate immune response in skeletal muscle. Lipopolysaccharide
      increases proinflammatory cytokine messenger RNA expression in muscle from
      control mice, but not from mice with a mutation in the lipopolysaccharide
      receptor. Lipopolysaccharide also increases cytokine expression in human and
      mouse myoblasts. Local expression of cytokines in skeletal muscle may negatively
      regulate the autocrine synthesis of IGF-I. Current work is focused on deciphering
      the mechanism by which muscle becomes GH resistant and the development of
      therapies to maintain muscle protein stores during infection.

PMID- 15471791
TI  - Management to reduce nitrogen losses in animal production.
AB  - Reduction of nitrogen loss in animal production requires whole-farm management.
      Reduced loss from one farm component is easily negated in another if all
      components are not equally well managed. Animal excretion of manure N can be
      decreased by improving the balance of protein or amino acids fed to that required
      by individual animals or animal groups or by improving production efficiency.
      Management to increase milk, meat, or egg production normally improves efficiency
      by reducing the maintenance protein required per unit of production. Large losses
      of manure nitrogen occur through the ammonia and nitrous oxide that are emitted
      into the atmosphere and the nitrate leached into groundwater. Up to half of the
      excreted nitrogen is lost from the housing facility, but this loss can be
      decreased through frequent manure removal and by avoiding deep litter systems and
      feedlots. Techniques such as acid treatment of manure, scrubbing of ventilation
      air, and floor designs for separating feces and urine substantially reduce
      ammonia emissions, but these practices are often impractical or uneconomical for
      general use. Manure storage units improve nutrient utilization by allowing better
      timing of nutrient application with crop needs. At least 70% of the nitrogen
      entering anaerobic lagoons is typically lost, but a less than 10% loss can be
      maintained using slurry storage with a natural crust or other cover, or by drying
      poultry manure to at least 50% dry matter. Irrigation and surface spreading of
      manure without soil incorporation often ensures the loss of all remaining
      nonorganic nitrogen (typically, 20 to 40% of remaining nitrogen). Rapid
      incorporation and shallow injection methods decrease this loss by at least 50%,
      and deep injection into the soil essentially eliminates this loss. For grazing
      animals, excessive loss can be avoided by not overstocking pastures and avoiding
      late fall and winter grazing. Reducing emissions between the animal and the soil
      can lead to greater leaching and denitrification losses from the soil if this
      additional nitrogen is not used properly. The use of a crop rotation that
      efficiently absorbs these nutrients and applying nitrogen near the time it is
      needed by crops reduce the potential for further loss. Maintaining the proper
      number of animals per unit of land available for manure application is always
      crucial for efficient recycling of nitrogen. Our understanding of nitrogen loss
      processes is improved through modeling, and computer models assist in the
      development of integrated systems for efficient and economical nitrogen use in
      animal production.

PMID- 15471792
TI  - Is rangeland agriculture sustainable?
AB  - The objective of this paper is to examine the sustainability of rangeland
      agriculture (i.e., managed grazing) on a world-wide basis, with a focus on North
      America. Sustainability is addressed on three fronts: 1) ecological, 2) economic,
      and 3) social acceptance. Based on previous and on-going research, we suggest
      that employment of science-based rangeland grazing management strategies and
      tactics can ensure ecological sustainability. The formidable challenge in
      employing such technology centers around the need to balance efficiency of solar
      energy capture and subsequent harvest efficiencies across an array of highly
      spatially and temporally variable vegetation growing conditions using animals
      that graze selectively. Failure to meet this fundamental challenge often
      accelerates rangeland desertification processes, and in some instances, enhances
      rate and extent of the invasion of noxious weeds. We also suggest that the
      fundamental reason that ecologically sound grazing management technologies are
      often not employed in the management of grazed ecological systems is because
      social values drive management decisions more so than ecological science issues.
      This is true in both well-developed societies with substantial economic resources
      and in less-developed societies with few economic resources. However, the social
      issues driving management are often entirely different, ranging from multiple-use
      issues in developed countries to human day-to-day survival issues in poorly
      developed countries. We conclude that the long-term sustainability of rangeland
      agriculture in 1) developed societies depends on the ability of rangeland
      agriculturalists to continually respond in a dynamic, positive, proactive manner
      to ever-changing social values and 2) less-developed societies on their ability
      to address the ecological and social consequences arising from unsustainable
      human populations before the adoption of science-based sustainable rangeland
      management technologies.

PMID- 15471794
TI  - Management strategies for optimal grazing distribution and use of arid
      rangelands.
AB  - Application of existing and novel management techniques can alter traditional
      livestock grazing patterns and significantly improve the sustainability of arid
      rangelands. Livestock often congregate and heavily graze riparian areas and other
      sensitive rangeland, while abundant forage remains in other areas. Increasing the
      uniformity of grazing can help protect fisheries, wildlife habitat, and other
      vegetative and watershed resources. For years, managers have improved grazing
      distribution in extensive arid pastures by developing new water sources. In
      addition, strategic supplement placement can be used to lure cattle to graze
      areas that typically receive little use. Placement of low-moisture molasses
      blocks in steeper areas that were far from water increased forage use by 14% at
      distances up to 600 m from supplement in foothill rangeland. Recent research has
      examined the potential of breed and individual animal selection to improve
      grazing distribution patterns. Cattle breeds developed in mountainous terrain
      utilize rugged rangeland more uniformly than breeds developed in more gentle
      terrain. In pastures that were grazed by cattle identified as "hill climbers"
      (previously observed on rugged terrain), more residual vegetation was left on
      gentle slopes and areas closer to water than in pastures grazed by cattle
      identified as "bottom dwellers" (previously observed on gentle terrain near
      water). Cattle may use rugged rangeland more uniformly after weaning and during
      periods when temperatures are more moderate and the forage is more homogeneous
      (spring, early summer, and autumn). Herding shows great promise for protecting
      sensitive rangeland. Preliminary data show that residual riparian forage in
      pastures where livestock were herded was up to two times higher than in a control
      pasture. The integration of herding and strategic supplement placement seems to
      be more effective than herding alone. Many concerns associated with the
      sustainability of grazing on arid rangelands can be resolved by manipulating
      livestock grazing behavior through management.

PMID- 15471793
TI  - The effect of oocyte quality on development.
AB  - Oocyte quality affects early embryonic survival, the establishment and
      maintenance of pregnancy, fetal development, and even adult disease. Quality, or
      developmental competence, is acquired during folliculogenesis as the oocyte
      grows, and during the period of oocyte maturation. Assisted reproductive
      technologies involving ovarian hyperstimulation, or collection of immature
      oocytes followed by maturation in vitro, perturb this process and result in
      oocytes with reduced quality. In domestic livestock species, offspring have been
      produced using in vitro oocyte maturation, although only a small percentage of
      the original pool of immature oocytes is capable of developing to the blastocyst
      stage and subsequently resulting in pregnancy. In vitro maturation, as it is
      currently undertaken, does not support the correct development of oocyte
      competence. Follicle size affects oocyte quality, potentially implicating
      messenger RNA or protein stores as factors involved in oocyte competence. Oocytes
      from preantral follicles grown in vitro are competent to resume meiosis, although
      development to the blastocyst stage is decreased. An offspring from oocytes
      produced using this technique was normal at birth but experienced delayed onset
      health issues, highlighting the importance of oocyte quality long after
      embryogenesis. Metabolism may play a critical role in oocyte quality because
      glycolytic activity in mature oocytes is correlated with increased embryonic
      development. Communication between the oocyte and its surrounding cumulus cells
      is also important for the development of a competent oocyte. Ovarian stimulation
      causes delayed embryonic development, increased abnormal blastocyst formation,
      fetal growth retardation, and increased fetal loss. Thus, although meiosis and
      even early development may be completed successfully, there are a variety of
      other processes occurring within the cytoplasm of the oocyte that are required
      for complete developmental competence. However, the cellular mechanisms that
      impart oocyte quality are unclear. Until the mechanisms involved in oocyte
      quality are elucidated, any effort to use assisted reproductive technologies in
      animals for production or biomedical purposes will be inefficient at best.

PMID- 15471795
TI  - Fat supplementation and reproduction in beef females.
AB  - Inadequate dietary energy intake and poor body condition can negatively affect
      reproductive function. Supplemental lipids have been used to increase energy
      density of the diet and may also have direct positive effects on reproduction in
      beef cattle. Several fatty acid sources have been studied as they relate to
      reproductive function. Common sources include sunflower, safflower, cottonseed,
      rice bran, soybeans, fishmeal, animal tallow, and calcium salts of fatty acids.
      Fats have been fed before and after calving, during the breeding season, and
      during heifer development. Response to fat has been investigated through
      measuring body weight and body condition score, age at puberty, postpartum
      interval, first-service conception rates, pregnancy rates, calving interval,
      calving difficulty, and calf birth and weaning weight. Animal response seems to
      depend on body condition score, age (parity), nutrients available in the diet,
      and type of fat supplemented. To elucidate potential mechanisms of action,
      scientists have investigated changes in follicular and uterine development,
      hormonal profiles, brain function, and embryonic development. Feeding
      supplemental fat has resulted in varied and inconsistent effects on reproductive
      function. Elucidating how supplemental fat can influence reproductive function
      has been a difficult process. The complexity of the reproductive system and
      makeup of fat supplements are often confounded by management conditions and
      forage quality both in research and commercial feeding situations.

PMID- 15471796
TI  - Experimental design and statistical methods for classical and bioequivalence
      hypothesis testing with an application to dairy nutrition studies.
AB  - Genetically modified (GM) corn hybrids have been recently compared against their
      isogenic reference counterparts in order to establish proof of safety as
      feedstuffs for dairy cattle. Most such studies have been based on the classical
      hypothesis test, whereby the null hypothesis is that of equivalence. Because the
      null hypothesis cannot be accepted, bioequivalence-testing procedures in which
      the alternative hypothesis is specified to be the equivalence hypothesis are
      proposed for these trials. Given a Type I error rate of 5%, this procedure is
      simply based on determining whether the 90% confidence interval on the GM vs.
      reference hybrid mean difference falls between two limits defining equivalence.
      Classical and bioequivalence power of test are determined for 4 x 4 Latin squares
      and double-reversal designs, the latter of which are ideally suited to
      bioequivalence studies. Although sufficient power likely exists for classical
      hypothesis testing in recent GM vs. reference hybrid studies, the same may not be
      true for bioequivalence testing depending on the equivalence limits chosen. The
      utility of observed or retrospective power to provide indirect evidence of
      bioequivalence is also criticized. Design and analysis issues pertain to Latin
      square and crossover studies in dairy nutrition studies are further reviewed. It
      is recommended that future studies should place greater emphasis on the use of
      confidence intervals relative to P-values to unify inference in both classical
      and bioequivalence-testing frameworks.

PMID- 15471797
TI  - Animal management to reduce phosphorus losses to the environment.
AB  - Water quality in the United States is threatened by contamination with nutrients,
      primarily nitrogen and phosphorus. Animal manure can be a valuable resource for
      farmers, providing nutrients, improving soil structure, and increasing vegetative
      cover to decrease erosion potential. At the same time, application of manure
      nutrients in excess of crop requirements can result in environmental
      contamination. Environmental concerns with P are primarily associated with
      pollution of surface water (streams, lakes, rivers). This pollution may be caused
      by runoff of P when application to land is in excess of crop requirements.
      Increased specialization and concentration of livestock and crop production has
      led to the net export of nutrients from major crop-producing areas of the country
      to areas with a high concentration of animal agriculture. Concentrated animal
      agriculture has been identified as a significant source of P contamination of
      surface water. Areas facing the dilemma of an economically important livestock
      industry concentrated in an environmentally sensitive area have few options. If
      agricultural practices continue as they have in the past, continued damage to
      water resources and a loss of fishing and recreational activity are inevitable.
      If agricultural productivity is decreased, however, the maintenance of a stable
      farm economy, a viable rural economy, and a reliable domestic food supply are
      seriously threatened. Decreasing the P content of manure through nutrition is a
      powerful, cost-effective approach to reducing P losses from livestock farms and
      will help farmers meet increasingly stringent environmental regulations. This
      paper reviews opportunities available to reduce the P content of livestock
      manure, including more accurate interpretation of the published P requirements of
      animals, improved diet formulation and group-feeding strategies to more precisely
      meet requirements, and approaches to improve availability of feed P for
      monogastric and ruminant species.

PMID- 15471798
TI  - Governmental policies and measures regulating nitrogen and phosphorus from animal
      manure in European agriculture.
AB  - This paper discusses governmental policies and measures that regulate the use of
      animal manure in the European Union (EU-15). Systematic intervention by
      governments with European agriculture in general started at the end of the 19th
      century. Major changes in governmental policies on agriculture followed after the
      establishment of the EU and its Common Agricultural Policy (CAP) in 1957.
      Environmental side effects of the large-scale intensification of agricultural
      production were addressed following the reform of the CAP and the implementation
      of various environmental regulations and directives from the beginning of the
      1990s. The Nitrate Directive approved in 1991 has exerted, as yet, the strongest
      influence on intensive livestock production systems. This directive regulates the
      use of N in agriculture, especially through its mandatory measures to designate
      areas vulnerable to nitrate leaching and to establish action programs and codes
      of good agricultural practice for these areas. These measures have to ensure that
      for each farm the amount of N applied via livestock manure shall not exceed 170
      kg x ha(-1) x yr(-1). These measures have large consequences, especially for
      countries with intensive animal agriculture, including The Netherlands, Belgium,
      Denmark, and Ireland. The mean livestock density in these countries is between
      1.5 and 4 livestock units/ha, and the average amounts of N in animal manure range
      from 100 to 300 kg/ha of agricultural land. More than 10 yr after approval of the
      Nitrate Directive, there appears to be a delay in the implementation and
      enforcement in many member states, which reflects in part the major complications
      that arise from this directive for intensive livestock farming. It also reflects
      the fact that environmental policies in agriculture have economic consequences.
      The slow progress in the enforcement of environmental legislations in agriculture
      combined with the increasing public awareness of food safety, animal welfare, and
      landscape maintenance call for a more fundamental change in EU agriculture.

PMID- 15471799
TI  - Somatotropin regulation of protein metabolism in pigs.
AB  - A primary goal of exogenous somatotropin treatment is to increase lean body mass.
      This is accomplished, in part, by increasing the efficiency with which dietary
      amino acids are used for protein deposition. Somatotropin administration also
      improves protein balance by minimizing the loss of protein during fasting and
      maximizing the protein gained during meal absorption. Amino acid catabolism is
      decreased by somatotropin treatment, as indicated by decreases in blood urea
      nitrogen, urea synthesis, hepatic urea cycle enzyme activity, and amino acid
      oxidation. Stable isotope tracer/mass transorgan balance studies have recently
      demonstrated that somatotropin treatment increases protein anabolism in young,
      growing swine by increasing protein synthesis in the hind limb and portal-drained
      viscera in the fed state, with little effect on protein degradation. Detailed
      study of the tissue-specific responses indicates that somatotropin treatment
      increases protein synthesis in skeletal muscle by increasing the efficiency of
      the translational process, but only in the fed state. The somatotropin-induced
      stimulation of skeletal muscle protein synthesis involves mechanisms that enhance
      the binding of both mRNA and initiator methionyl-tRNA to the 40S ribosomal
      subunit. Somatotropin increases protein synthesis in the liver in both the fasted
      and fed states by increasing ribosome number, with no change in translation
      initiation. Thus, the protein synthetic response to somatotropin treatment is
      tissue-specific and dependent on nutritional state.

PMID- 15471800
TI  - Power of test considerations for beef cattle experiments: a review.
AB  - The use of power tests in the planning and design of beef cattle experiments
      provides critical information on sample sizes necessary to detect treatment
      differences at a predetermined significance (alpha) level. Retrospective power
      analysis provides additional information about previous experiments that may be
      helpful in designing subsequent investigations. However, in retrospective power
      analyses, power is inversely related to observed significance level. Benefits of
      prospective and retrospective power analyses in beef cattle experiments are
      similar to those for other species; however, because of differences in the
      methods and conditions involved, considerations for the use of power test
      procedures are specific for beef cattle research. Retrospective power analyses
      were conducted on 78 published experiments and on two unpublished experiments.
      Experiments were compiled into categories that represented group (or pen)
      feeding, individual feeding, and metabolism studies. Estimated power in pen
      feeding experiments using randomized block designs (RBD, n = 30) was less than
      0.80 for ADG and feed efficiency (FE), but not different from 0.80 for completely
      random designs (CRD, n = 4). Furthermore, estimated power was less for ADG than
      for FE in both design types. For individual feeding experiments using RBD (n =
      4), power was not different from 0.80 for either ADG or FE; however, for CRD (n =
      18), power was less than 0.80 for both ADG and FE. Power was similar for ADG and
      FE for both RBD and CRD in individual feeding experiments. In metabolism
      experiments, estimated power for nitrogen retention was less than 0.80 for Latin
      square designs (n = 20) but not for CRD (n = 4). Comparisons of power between
      experimental design types were likely influenced by the number of experiments
      involved. These results indicate that retrospective power in beef cattle
      experiments is affected by design type, and response variable measured.

PMID- 15471801
TI  - Designing trials to test the bioequivalence of diets for animal performance.
AB  - It is usually the desire of the researcher to demonstrate a difference in the
      comparisons made. This is certainly the case when an improved product is desired.
      However, in establishing the bioequivalence of a test product to a standard, the
      objective is usually to conclude, with reasonable justification, that no
      difference has been detected. In making such determinations, the probabilities of
      accepting false hypotheses or those of rejecting correct hypotheses of difference
      must be taken into account. Before beginning the trial, the researcher should
      have a good estimate of the power that will be associated with the detection of a
      given minimum acceptable difference. The required sample size for achieving the
      desired power for these tests depends on the coefficient of variation in the data
      collected and the minimum detectable difference between two groups that the study
      is meant to detect. It is important to determine the relative magnitudes of the
      sampling and the experimental errors in order to decide, for a given number of
      animals available for the study, how they might be best subdivided into groups
      within treatment. This paper addresses these points and others in an attempt to
      summarize some of the key items that researchers should consider when planning
      trials for the bioequivalence testing of new products.

PMID- 15471802
TI  - Energy value of pig feeds: effect of pig body weight and energy evaluation
      system.
AB  - Ad libitum energy intake and performance in pigs depends on many animal and
      environmental factors in which feed energy density plays an important role. In
      addition, feed represents an important cost in pig production, and energy
      represents the greatest proportion of this cost. It is therefore important to
      express the feed energy value on an appropriate basis, and both energy supply (a
      dietary characteristic) and energy requirement (an animal characteristic) should
      be expressed using the same system. Energy content depends first on the nutrient
      composition; the constituents differ markedly in GE content (23.0, 39.0, 17.4,
      and 18.4 kJ/g for CP, fat, starch, and dietary fiber, respectively). Due to
      differences in digestibility and associated endogenous energy losses, the actual
      contribution of nutrients to apparent DE supply in growing pigs is even more
      variable and ranges from 31.7 kJ/g for fat, 22.4 kJ/g for CP, 17.2 kJ/g for
      starch, to only 3.2 kJ/g for dietary fiber. Nutrient composition also affects the
      efficiency of conversion of ME to NE, which varies from 90% for fat to 82% for
      starch and 60% for CP. Consequently, the energy values (relative to a
      conventional diet containing 14.2, 13.6, and 10.3 MJ/kg of DE, ME, and NE,
      respectively) of corn, soybean meal, and animal fat are 100, 104, and 235 on a DE
      basis; 102, 99, and 244 on a ME basis; and 107, 79, and 289 on a NE basis. Energy
      value thus depends on the system of evaluation. The energy density of pig feeds
      can also be affected by feed processing. For example, pelleting markedly
      increases fat and energy digestibilities in corn or full-fat rapeseed. Also the
      animal itself can affect the energy value of nutrients; digestion of dietary
      fiber becomes more efficient with increasing BW, with subsequent differences in
      energy content of feeds according to BW. In conclusion, a satisfactory
      characterization of the energy value of feeds should be based on their NE
      content. Factors affecting nutrients digestibility (e.g., BW and feed processing)
      should also be taken into account.

PMID- 15471803
TI  - Somatotropic function: the somatomedin hypothesis revisited.
AB  - The discovery in 1922 that an alkaline extract of the anterior pituitary can
      increase growth and change carcass composition of rats led to the discovery of
      growth hormone (somatotropin, ST). Since the early studies, much has been learned
      about the biological effects of ST. The advent of recombinant DNA technology has
      led to the commercial development of ST-based products for animal agriculture.
      Administration of porcine ST (pST) at maximally effective doses (approximately
      100 microg x kg BW(-1) x d(-1)) to growing pigs for 30 to 77 d increases average
      daily gain approximately 10 to 20%, improves productive efficiency (i.e., the
      ratio of body weight gain to feed consumed) 13 to 33%, decreases lipid accretion
      rates by as much as approximately 80%, and stimulates protein deposition (muscle
      growth) by as much as 70%. These responses are associated with a decrease in feed
      intake of approximately 10 to 15%. The effects of ST are mediated directly and
      indirectly. The indirect effects of ST are mediated by the somatomedin (insulin
      like growth factor-I). The discovery of somatomedin led to the introduction of
      the somatomedin hypothesis, which explained the basis of ST action. Since the
      discovery of the somatomedins, there have been several modifications of the
      hypothesis developed to accommodate the evolution in understanding of how ST and
      IGF-I affect a diverse array of biological events. This review will summarize the
      history of ST and the evolution of the somatomedin hypothesis.

PMID- 15471805
TI  - How many pigs? Statistical power considerations in swine nutrition experiments.
AB  - Replication refers to the assignment of more than one experimental unit to the
      same treatment. Each replication of a treatment is an independent observation;
      thus, each replication involves a different experimental unit. In swine nutrition
      research, the experimental unit may be an individual animal, as in sow
      reproduction experiments, or a group of animals, as in growing-finishing pig
      experiments. In either case, calculation of the number of replicates needed to
      give an accurate and reliable outcome is an important step in deriving an
      experimental protocol. Although investigators often seem to choose replication
      arbitrarily on the basis of cost or availability of animals, housing
      considerations, convenience, or tradition, the question of how many pigs (i.e.,
      how much replication is necessary) is a statistical one that has a statistical
      answer. A power analysis, performed while designing an experiment, will provide
      an investigator with an estimate of the number of replicates needed for an
      experiment of known power and sensitivity. This a priori, or prospective, power
      analysis ensures that an investigator does not waste time and resources carrying
      out an experiment that has little chance of finding a significant effect, if one
      exists. It also makes sure resources are not wasted by including more
      experimental units than are necessary to detect an effect. A retrospective, or a
      posteriori, power analysis may also be conducted. If no significant effects are
      found in an experiment, an investigator can assess the observed power of the
      experiment, or may determine the size of treatment effect that could have been
      detected using the standard deviation and number of replicates in the experiment.
      The latter may be useful in explaining results. However, the former may be
      misleading because a high P-value will invariably result in a low observed power,
      and little new information will be gained from the post hoc power analysis. In
      most cases, the time for making power calculations is before, not after, an
      experiment is conducted.

PMID- 15471804
TI  - Preovulatory, postovulatory, and postmaternal recognition effects of
      concentrations of progesterone on embryonic survival in the cow.
AB  - Although fertilization rate usually is very high when male fertility is normal,
      pregnancy rates are below expectations when defined by the birth of live
      offspring in response to first service. Factors that affect establishment and
      retention of pregnancy include 1) preovulatory influences on the follicle and
      oocyte, 2) early postovulatory uterine and luteal function, 3) concentrations of
      hormones associated with trophoblastic and endometrial function during maternal
      recognition of pregnancy, and 4) less-well understood factors during the peri
      attachment period. For example, decreased progesterone during preovulatory
      follicular development leads to a persistent follicle, premature resumption of
      meiosis, and a high incidence of embryonic death between the 2- and 16-cell
      stages. Elevated PGF(2alpha) during d 4 to 9 of the estrous cycle not only caused
      luteolysis but also had a direct embryotoxic effect during the morula-to
      blastocyst transition. Ideal conditions during placentation and attachment are
      not clearly defined. Late embryonic mortality might be increased after ovulation
      of persistent or immature follicles. Nominal increases in secretion of
      PGF(2alpha) between d 30 and 35 might be important for attachment and
      placentation. Lower survival of embryos from wk 5 to wk 7 to 9 of gestation in
      the cow was associated with lower circulating concentrations of progesterone on
      wk 5. To maximize embryonic survival in the cow, management must provide high
      progesterone before estrus, quality detection of estrus, and timely insemination.
      Luteolytic influences of estradiol-17beta or PGF(2alpha) must be minimized early
      after mating and during maternal recognition of pregnancy, and high progesterone
      is needed during the late embryonic/early fetal period.

PMID- 15471806
TI  - Water quality and the grazing animal.
AB  - Grazing animals and pasture production can affect water quality both positively
      and negatively. Good management practices for forage production protect the soil
      surface from erosion compared with conventionally produced crops. Grazing animals
      and pasture production can negatively affect water quality through erosion and
      sediment transport into surface waters, through nutrients from urine and feces
      dropped by the animals and fertility practices associated with production of high
      quality pasture, and through pathogens from the wastes. Erosion and sediment
      transport is primarily associated with high-density stocking and/or poor forage
      stands. The two nutrients of primary concern relating to animal production are N
      and P. Nitrogen is of concern because high concentrations in drinking water in
      the NO(3) form cause methemoglobinemia (blue baby disease), whereas other forms
      of N (primarily nitrite, NO(2)) are considered to be potentially carcinogenic.
      Phosphorus in the PO(4) form is of concern because it causes eutrophication of
      surface water bodies. The effect of grazing animals on soil and water quality
      must be evaluated at both the field and watershed scales. Such evaluation must
      account for both direct input of animal wastes from the grazing animal and also
      applications of inorganic fertilizers to produce quality pastures. Watershed
      scale studies have primarily used the approach of nutrient loadings per land area
      and nutrient removals as livestock harvests. A number of studies have measured
      nutrient loads in surface runoff from grazed land and compared loads with other
      land uses, including row crop agriculture and forestry. Concentrations in
      discharge have been regressed against standard grazing animal units per land
      area. Watersheds with concentrated livestock populations have been shown to
      discharge as much as 5 to 10 times more nutrients than watersheds in cropland or
      forestry. The other major water quality concern with grazing animals is
      pathogens, which may move from the wastes into surface water bodies or ground
      water. Major surface water quality problems associated with pathogens have been
      associated with grazing animals, particularly when they are not fenced out from
      streams and farm ponds. This paper presents an overview of water quality issues
      relating to grazing animals.

PMID- 15471807
TI  - A new plasmid-mediated approach to supplement somatotropin production in pigs.
AB  - Tremendous progress has been made in the identification of the stimulatory
      molecules that regulate growth, the mechanisms of action, and the potential
      application of these molecules for livestock production. A parallel and
      significant effort is now focused on the discovery and development of
      economically feasible gene delivery technologies. Plasmid-mediated GHRH gene
      transfer has emerged as an excellent candidate for agricultural applications to
      optimize production and animal welfare. We have engineered a GHRH-expressing
      plasmid that is efficiently expressed in skeletal muscle following intramuscular
      injection enhanced by electroporation. The GHRH is synthesized in the injected
      muscle, from which it is secreted to circulate and stimulate normal pituitary GH
      production and release. Young pigs directly injected with as little as 0.1 mg of
      a GHRH-expressing plasmid had greater (P < 0.01) weight gain than controls, and a
      increase (P < 0.05) in fat-free mass. We also have demonstrated that the
      offspring of gilts injected intramuscularly at d 85 of gestation with a GHRH
      expressing plasmid have optimized growth characteristics due to both improved
      intrauterine weight gain and enhanced maternal lactation performance. Thus, the
      piglets from treated gilts were larger at birth and weaning compared to controls
      and reached market weight earlier (P < 0.001). Additionally, pituitaries
      collected from this group contained an increased number of somatotrophs and
      lactotrophs (P < 0.001) at birth and at 100 kg. An additional advantage of
      administering the GHRH plasmid to the gilt compared with the administration of
      growth-promoting agents to the individual adult animal is a substantial decrease
      in offspring morbidity and mortality (P < 0.01), which has always represented a
      major economic loss for the swine industry.

PMID- 15471808
TI  - An update on estrus synchronization in goats: a minor species.
AB  - Estrus synchronization allows for parturition at suitable times to take advantage
      of niche markets, feed supplies, labor, and rising price trends. In the past,
      synchronization of estrus in goats has focused primarily on dairy goats to allow
      for optimal timing of milk production. However, recent interest in meat goat
      production has resulted in attempts to use dairy goat, sheep, and cattle
      synchronization regimens in meat goat management systems. Methods of
      synchronization have included techniques as simple as alteration of light
      patterns or manipulation of social inputs (i.e., the buck effect) and as complex
      as varying timed hormonal treatments combined with light alteration and the buck
      effect. The synchronization of estrus using timed hormonal treatments seems to be
      more convenient in many meat goat production situations. Examples of hormones
      used include melatonin, progestogens (administered orally, as an injection, or by
      using intravaginal releasing devices), gonadotropins/GnRH (or agonists), and PG
      alone or in combination. As is seen with sheep and cattle, breed and/or breed
      type, stage of production, and environmental effects can influence
      synchronization success in goats. The introduction of breeds developed in other
      countries for rapid growth, such as the Boer goat, and increased consumer and
      producer interest have added to the impetus for developing cost-efficient and
      highly effective estrus synchronization regimens. New research is being conducted
      and various synchronization methods are being attempted in goats, a minor
      species, and the objective of this paper is to review these efforts.

PMID- 15471809
TI  - Technical basis for quantifying phosphorus transport to surface and groundwaters.
AB  - Decreasing the potential delivery of phosphorus in fertilizers or animal waste to
      surface and groundwater requires a knowledge of phosphorus's fate and transport
      mechanisms. The USDA Natural Resources Conservation Service has recently mandated
      each state to develop an assessment tool to estimate P transport to water bodies.
      The objective of this paper is to describe the processes involved with P
      transport to surface and groundwaters that must be accounted for in practical
      methods used to quantify the potential for P loss. Mechanistic models to assess P
      loss should account for: 1) P adsorbed to eroding sediments, 2) soluble P in
      runoff water, 3) soluble P in leaching water, and 4) P losses related to specific
      P sources. With sediment-bound P, the adsorbed P content in the eroded soil mass
      at the field edge must be quantified, whereas runoff volume and P concentration
      are needed to estimate soluble P loss in runoff water. Estimating P leaching
      potential requires calculation of drainage water volume and P concentration. When
      P is applied in animal waste, the specific source influences both soluble and
      particulate P loss because of differences in P solubility between waste types. In
      addition, the effects of conservation practices and other technologies on
      decreasing sediment, soluble, and leached P need to be included. Using these
      methods, a practical, quantitative P loss assessment tool can be developed that
      will enable technical service providers and other practitioners to estimate
      potential P loss and design best-management practices for land-applied waste
      management systems in order to minimize P transport to surface and groundwater.

PMID- 15471810
TI  - Microarrays and beyond: what potential do current and future genomics tools have
      for breeders?
AB  - One of the most exciting tools from genomics is the ability to obtain a whole
      genome snapshot of gene expression. This is typically called a microarray
      analysis, because probes for the genes of interest, which can run into the
      thousands, are spotted in a very small array on a glass slide or some other
      substrate. The resulting array is often called a gene chip, or simply a chip, in
      the case of short oligo arrays, or slides in the case of cDNA or long oligo
      arrays. Microarrays offer the awesome potential of simultaneously examining the
      level of expression, where expression is intended to measure the standing amount
      of mRNA, for all of the genes in a genome. Given this potential, it is not
      surprising that microarrays have attracted a great deal of attention from animal
      geneticists and breeders. The purpose of this review is to provide a brief, yet
      critical, overview of some of the potential uses of such whole-genome expression
      studies in applied animal breeding and to speculate about what additional
      forthcoming tools might be of use.

PMID- 15471811
TI  - Quantitative genomics: exploring the genetic architecture of complex trait
      predisposition.
AB  - Most phenotypes with agricultural or biomedical relevance are multifactorial
      traits controlled by complex contributions of genetics and environment. Genetic
      predisposition results from combinations of relatively small effects due to
      variations within a large number of genes, known as QTL. Well over 200 QTL have
      been reported for growth and body composition traits in the mouse, which likely
      represent at least 50 to 100 distinct genes. Molecular biology has yielded
      significant advances in understanding these traits at the metabolic and
      physiological levels; however, little has been learned regarding the identity and
      nature of the underlying polygenes. In addition to the significantly poor
      precision inherent to QTL localization, it is very difficult to differentiate
      between co-localization and coincidence when comparing QTL with other QTL and
      with potential candidate genes. The wide gap between our knowledge of
      physiological mechanisms underlying complex traits and the nature of genetic
      predisposition significantly impairs discovery of genes underlying QTL.
      Identification and genetic mapping of key transcriptional, proteomic,
      metabolomic, and endocrine events will uncover large lists of significant
      positional candidate genes for growth and body composition. However, integration
      of experimental approaches to jointly evaluate predisposition and physiology will
      increase success of QTL identification by merging the power of recombination with
      functional analysis. Measuring physiologically relevant subphenotypes within a
      structured QTL mapping population will not only facilitate pathway-specific
      prioritization among candidate genes, but may also directly identify genes
      underlying QTL. This would advance our understanding of the genetic architecture
      of complex traits by testing the central hypothesis that genes controlling
      predisposition to a quantitative trait are primarily involved in trans-regulation
      of the primary physiological pathways that regulate the trait.

PMID- 15471812
TI  - Commercial application of marker- and gene-assisted selection in livestock:
      strategies and lessons.
AB  - During the past few decades, advances in molecular genetics have led to the
      identification of multiple genes or genetic markers associated with genes that
      affect traits of interest in livestock, including genes for single-gene traits
      and QTL or genomic regions that affect quantitative traits. This has provided
      opportunities to enhance response to selection, in particular for traits that are
      difficult to improve by conventional selection (low heritability or traits for
      which measurement of phenotype is difficult, expensive, only possible late in
      life, or not possible on selection candidates). Examples of genetic tests that
      are available to or used in industry programs are documented and classified into
      causative mutations (direct markers), linked markers in population-wide linkage
      disequilibrium with the QTL (LD markers), and linked markers in population-wide
      equilibrium with the QTL (LE markers). In general, although molecular genetic
      information has been used in industry programs for several decades and is
      growing, the extent of use has not lived up to initial expectations. Most
      applications to date have been integrated in existing programs on an ad hoc
      basis. Direct markers are preferred for effective implementation of marker
      assisted selection, followed by LD and LE markers, the latter requiring within
      family analysis and selection. Ease of application and potential for extra
      genetic gain is greatest for direct markers, followed by LD markers, but is
      antagonistic to ease of detection, which is greatest for LE markers. Although the
      success of these applications is difficult to assess, several have been hampered
      by logistical requirements, which are substantial, in particular for LE markers.
      Opportunities for the use of molecular information exist, but their successful
      implementation requires a comprehensive integrated strategy that is closely
      aligned with business goals. The current attitude toward marker-assisted
      selection is therefore one of cautious optimism.

PMID- 15471813
TI  - Uterine and placental factors regulating conceptus growth in domestic animals.
AB  - All mammalian uteri contain endometrial glands that synthesize or transport and
      secrete substances essential for survival and development of the conceptus
      (embryo/fetus and associated extraembryonic membranes). The ovine uterine gland
      knockout ewe model supports a primary role for endometrial glands and, by
      default, their secretions as essential for conceptus survival and development
      during the peri-implantation period of pregnancy. Endometrial adenogenesis, the
      process whereby glands develop in the uterus, is primarily a postnatal event in
      domestic and laboratory animals, as well as in humans. Endometrial adenogenesis
      involves differentiation and budding of glandular epithelium from lumenal
      epithelium, followed by invagination and extensive tubular coiling and branching
      morphogenesis throughout uterine stroma to the myometrium. In sheep, pituitary
      prolactin acting on prolactin receptors expressed by uterine glandular epithelium
      regulates endometrial adenogenesis. In contrast, expression and functional
      activation of estrogen receptor alpha in the uterus is a primary regulator of
      endometrial adenogenesis in the pig. In adult sheep and pigs, extensive
      endometrial gland hyperplasia and hypertrophy occur during gestation, presumably
      to provide increasing histotrophic support for conceptus growth and development.
      A servomechanism has been proposed in sheep and pigs to regulate endometrial
      gland development and differentiated function during pregnancy that involves
      sequential actions of ovarian steroid hormones, pregnancy recognition signals,
      and lactogenic hormones from the pituitary and/or placenta. The fact that
      disruption of uterine development during critical organizational periods can
      alter the functional capacity and embryotrophic potential of the adult uterus
      reinforces the importance of understanding uterine developmental biology. Defects
      in endometrial gland morphogenesis during uterine growth and development may
      cause the unexplained, high rates of peri-implantation embryonic loss in domestic
      animals and humans. Knowledge of the basic mechanisms regulating uterine
      development is expected to suggest means to increase uterine capacity, litter
      size, and neonatal survival, as well as ameliorate certain types of infertility.

PMID- 15471814
TI  - Ovarian follicular growth and atresia: the relationship between cell
      proliferation and survival.
AB  - Growth factors and steroids play an important role in the regulation of ovarian
      follicular development. In cattle, two of the earliest detectable differences
      between the healthy dominant follicle selected for development to the ovulatory
      stage and subordinate follicles destined to undergo atresia are the greater
      availability of IGF and the greater capacity to produce estradiol in the dominant
      follicle. We have shown that IGF-I and estradiol stimulate the proliferation of
      bovine granulosa cells in vitro and promote granulosa cell survival by increasing
      resistance to apoptosis. Furthermore, the ability of IGF-I and estradiol to
      increase resistance to apoptosis is tied to their ability to promote progression
      through the cell cycle. Blocking the cell cycle at the transition between the
      first gap phase and the DNA synthesis phase using a specific inhibitor prevented
      the protective effects of IGF-I and estradiol against apoptosis. Further
      experiments showed that the protective effect of IGF-I against apoptosis is
      mediated by the stimulation of phosphatidylinositol 3-kinase and its downstream
      target, protein kinase B/Akt. Constitutive activation of Akt by the infection of
      granulosa cells with a recombinant Akt adenovirus protected against apoptosis,
      and this effect also depended on cell cycle progression. These experiments show
      that the protective effect of estradiol and IGF-I against apoptosis depends on
      unperturbed progression through the cell cycle. Once follicles have developed to
      the preovulatory stage, the LH surge induces terminal differentiation of
      granulosa cells and withdrawal from the cell cycle. Bovine granulosa cells
      withdraw from the cell cycle by 12 h after the LH surge and become resistant to
      apoptosis, even in the absence of growth factors. Treatment with a progesterone
      receptor antagonist in vitro caused reentry of granulosa cells into the cell
      cycle and susceptibility to apoptosis, suggesting that induction of progesterone
      receptor expression by the LH surge is required for cell cycle withdrawal and
      resistance to apoptosis. In summary, the susceptibility of granulosa cells to
      apoptosis depends on the cell cycle. Proliferating granulosa cells in growing
      follicles depend on growth factors for survival, whereas cells that have
      terminally differentiated in response to the LH surge are resistant to apoptosis
      and relatively independent of growth factors for survival.

PMID- 15471815
TI  - Development of fetuses from in vitro-produced and cloned bovine embryos.
AB  - The establishment of in vitro fertilization and culture systems for mammalian
      embryos has facilitated the application of embryo technologies in research,
      industry, and clinical settings. Furthermore, the advent of cloning by nuclear
      transfer has significantly enhanced the potential for genetic modification of
      livestock. Based on studies in cattle, sheep, and mice, it has become apparent
      that embryos produced using these systems can differ in morphology and
      developmental potential compared with embryos produced in vivo. Referred to as
      "large offspring syndrome," these abnormalities in the development of fetuses,
      placentas, and offspring are particularly evident following transfer of cloned
      embryos, but they also occur in pregnancies from embryos produced using in vitro
      culture alone. The objective of this review is to examine the effects of in vitro
      production and cloning on bovine embryo and fetal development. Literature
      pertaining to preimplantation embryo, conceptus, and fetal development, as well
      as gene expression occurring at each of these three stages, is reviewed.
      Physiologic and genetic mechanisms that contribute to large offspring syndrome
      also are discussed.

PMID- 15471816
TI  - Control of follicular growth: local interactions and nutritional influences.
AB  - Regulation of ovarian activity is an integrated process encompassing both
      extraovarian signals and intrafollicular factors. Initiation of primordial
      follicle growth and the early stages of folliculogenesis can occur without
      gonadotropins, but FSH may affect the rate of preantral follicle growth. Antral
      follicle development from 1 to 4 mm in sheep and cattle is completely
      gonadotropin dependent. These recruited follicles express a range of mRNA
      encoding steroidogenic enzymes, gonadotropin receptors, and local regulatory
      factors and their receptors. 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. Locally produced growth factors,
      such as the IGF and members of the transforming growth factor-beta superfamily,
      work in concert with gonadotropins throughout the follicular growth continuum and
      can have significant effects on follicle selection. Environmental influences,
      such as changes in nutrition, also have an effect on ovarian activity. This can
      occur without significant variation in circulating gonadotropin concentrations
      and can be correlated with changes in circulating concentrations of metabolic
      hormones, including insulin, IGF-I, GH, and leptin. Nutrition can also affect the
      expression of mRNA encoding components of the ovarian IGF system to regulate the
      sensitivity/response of follicles toward gonadotropins. Hence, the roles of
      growth factors in follicular development and survival depend on gonadotropin
      status and differentiation state of the follicle. In conclusion, it is the
      integration of these extraovarian signals and intrafollicular factors that
      determine whether a follicle will continue to develop or be diverted into atretic
      pathways.

PMID- 15471817
TI  - Novel endophyte-infected tall fescue for growing beef cattle.
AB  - Tall fescue (Festuca arundinacea, Shreb.) is the predominant cool-season,
      perennial grass in the eastern half of the United States, and the majority is
      infected with the endemic endophyte (E+) Neotyphodium coenophialum, resulting in
      millions of dollars in revenues lost to the beef industry. Endophyte-free (E-)
      tall fescue was initially tapped as a "silver bullet" for the solution to fescue
      toxicosis, but drought intolerance and overgrazing have often resulted in nearly
      complete stand losses in 3 to 4 yr. Recently, the discovery of new endophytes
      that do not produce ergot alkaloids has resulted in the development of novel
      endophyte-infected (NE+), stress-tolerant tall fescue plants. These NE+ tall
      fescue plants combine the plant persistence advantages of E+ (infected) tall
      fescue with the animal performance advantages of an E- tall fescue. Controlled
      studies from several locations in the southern United States have shown that the
      three commercially available cultivars of NE+ tall fescue persist as well as E+
      tall fescues. Stocker cattle performance trials from five states have shown that
      the ADG in cattle grazing NE+ tall fescue was 47% greater than in cattle grazing
      E+ tall fescue and that cattle show no signs of fescue toxicosis. Economic
      evaluations of establishment cost and improved animal performance indicate that a
      stand of NE+ tall fescue would require 7 yr to pay off and begin to return profit
      to the enterprise if calves grazing E+ pasture are not discounted in price for
      fescue toxicosis at marketing. Average discounts at marketing for cattle showing
      signs of fescue toxicosis are $7.49/45.4 kg of BW. Assuming E+ cattle are
      discounted at sale and the quality of cattle is not decreased by the use of NE+
      tall fescue, a stand of NE+ tall fescue would require 3 yr to pay the expense of
      establishment and begin to return profit to the enterprise.

PMID- 15471818
TI  - Building beef cow nutritional programs with the 1996 NRC beef cattle requirements
      model.
AB  - Designing a sound cow-calf nutritional program requires knowledge of nutrient
      requirements, diet quality, and intake. Effectively using the NRC (1996) beef
      cattle requirements model (1996NRC) also requires knowledge of dietary degradable
      intake protein (DIP) and microbial efficiency. Objectives of this paper are to 1)
      describe a framework in which 1996NRC-applicable data can be generated, 2)
      describe seasonal changes in nutrients on native range, 3) use the 1996NRC to
      predict nutrient balance for cattle grazing these forages, and 4) make
      recommendations for using the 1996NRC for forage-fed cattle. Extrusa samples were
      collected over 2 yr on native upland range and subirrigated meadow in the
      Nebraska Sandhills. Samples were analyzed for CP, in vitro OM digestibility
      (IVOMD), and DIP. Regression equations to predict nutrients were developed from
      these data. The 1996NRC was used to predict nutrient balances based on the
      dietary nutrient analyses. Recommendations for model users were also developed.
      On subirrigated meadow, CP and IVOMD increased rapidly during March and April. On
      native range, CP and IVOMD increased from April through June but decreased
      rapidly from August through September. Degradable intake protein (DM basis)
      followed trends similar to CP for both native range and subirrigated meadow.
      Predicted nutrient balances for spring- and summer-calving cows agreed with
      reported values in the literature, provided that IVOMD values were converted to
      DE before use in the model (1.07 x IVOMD - 8.13). When the IVOMD-to-DE conversion
      was not used, the model gave unrealistically high NE(m) balances. To effectively
      use the 1996NRC to estimate protein requirements, users should focus on three key
      estimates: DIP, microbial efficiency, and TDN intake. Consequently, efforts
      should be focused on adequately describing seasonal changes in forage nutrient
      content. In order to increase use of the 1996NRC, research is needed in the
      following areas: 1) cost-effective and accurate commercial laboratory procedures
      to estimate DIP, 2) reliable estimates or indicators of microbial efficiency for
      various forage types and qualities, 3) improved estimates of dietary TDN for
      forage-based diets, 4) validation work to improve estimates of DIP and MP
      requirements, and 5) incorporation of nitrogen recycling estimates.

PMID- 15471819
TI  - What are we doing about Escherichia coli O157:H7 in cattle?
AB  - Many human foodborne illnesses can be caused by consumption of foodstuffs
      (including meat products) contaminated with pathogenic bacteria from animal
      intestinal contents or hides. Steps that have been taken in the slaughter plant
      to decrease the spread of foodborne pathogenic bacteria (e.g., hazard analysis
      and critical control point methods) have been very effective; however, meat
      products are still the source of foodborne bacterial human illnesses. Increasing
      numbers of human Escherichia coli O157:H7 illnesses have also been related to
      contact with animals or to water supplies contaminated by run-off from cattle
      farms. Thus, strategies that specifically target foodborne pathogenic bacteria in
      the animal at the farm or feedlot level have great potential to improve food
      safety and decrease human illnesses. In this review, we describe a broad range of
      live-animal intervention strategies, both probiotic and antipathogen.
      Additionally, we examine some of the effects of diet and management strategies on
      foodborne pathogenic bacterial populations. The use of antibiotics in food
      animals to decrease foodborne pathogens also will be briefly examined. Overall,
      the concurrent use of several of these preslaughter intervention strategies could
      synergistically decrease human illnesses by providing for additional barriers in
      a multiple-hurdle approach to improving food safety.

PMID- 15471820
TI  - Variation in the loss of seed dormancy during after-ripening of wild and
      cultivated rice species.
AB  - BACKGROUND AND AIMS: The aim of this paper was to verify the variation in the
      loss of seed dormancy during after-ripening and the interspecific and
      interpopulation variability in the degree of dormancy of seven wild and two
      cultivated rice species comprising 21 populations and two cultivars. METHODS:
      Four wild rice species from South America, Oryza glumaepatula, O. latifolia, O.
      grandiglumis and O. alta, and two O. sativa cultivars were tested in one
      experiment. In a second experiment, five wild species, O. punctata, O.
      eichingeri, O.rufipogon, O. latifolia and O. glumaepatula, and one cultivated
      species (O. glaberrima) were evaluated. Initial germination tests were performed
      soon after the seeds were harvested and subsequently at 2-month intervals, for a
      total of six storage periods in the first experiment and three in the second. All
      tests were conducted in the dark at a temperature of 27 degrees C. KEY RESULTS:
      Different patterns of after-ripening among populations within and between species
      were observed. CONCLUSIONS: The cultivated species (O. sativa and O. glaberrima)
      and, amongst the wild species, the tetraploids O. latifolia, O. grandiglumis and
      the diploids O. eichingeri and O. punctata, had weak dormancy, losing it
      completely 2 months after harvest, while O. rufipogon and O. glumaepatula
      exhibited pronounced dormancy. The latter showed different patterns of after
      ripening between populations indigenous to the Amazon region and those
      originating in the Paraguay River system. Seeds of Solimoes (Amazon) and Japura
      origin showed weak dormancy whereas those of Paraguay origin showed deep
      dormancy. Ecological differences among natural habitats may be involved in such
      differentiation.

PMID- 15471821
TI  - 18F-FDG PET imaging in posttherapy monitoring of cervical cancers: from diagnosis
      to prognosis.

PMID- 15471822
TI  - Functional changes after partial left ventriculectomy and mitral valve repair
      assessed by gated perfusion SPECT.
AB  - A myocardial remodeling in dilated cardiomyopathy (DCM) after partial left
      ventriculectomy (PLV) has been previously discussed. The aim of this study was to
      investigate the functional changes in the follow-up of patients with DCM
      undergoing PLV using electrocardiographically triggered perfusion SPECT (gated
      SPECT). METHODS: Twelve DCM patients (10 men, 2 women; 56 +/- 9 y [mean +/- SD]),
      after successful PLV and mitral valve repair (PLV-MVR), were monitored by gated
      SPECT and echocardiography. Gated SPECT quantified end-diastolic volumes (EDV),
      end-systolic volumes (ESV), myocardial and scar volumes, as well as ejection
      fraction (EF) preoperatively, early (38 +/- 28 d), and late (296 +/- 130 d) after
      PLV-MVR. RESULTS: EDV and ESV showed an immediate reduction after PLV-MVR (EDV
      from 542 +/- 90 mL to 350 +/- 81 mL, P < 0.001; ESV from 452 +/- 91 mL to 254 +/-
      79 mL, P < 0.001) with no significant change in the late follow-up (EDV late, 316
      +/- 63 mL; ESV late, 207 +/- 63 mL; both P = not significant vs. early follow
      up). PLV-MVR immediately improved EF (preoperative, 16.8% +/- 5.5%; early, 28.8%
      +/- 7.6%; P = 0.003) with no significant change in the late follow-up (36.0% +/-
      9.4%; P = not significant vs. early follow-up). CONCLUSION: In this highly
      selected DCM patient group, gated perfusion SPECT assessed early responses in
      volumes and EF after PLV-MVR. However, although statistically nonsignificant in
      the small patient group, ESV and EDV were further decreased, whereas EF improved
      toward 1 y, coinciding with the improvement of clinical symptoms (New York Heart
      Association), potentially indicating a functional remodeling after PLV-MVR.
      Further studies in larger patient cohorts and longer follow-up are warranted.

PMID- 15471824
TI  - A method to remove artifacts in attenuation-corrected myocardial perfusion SPECT
      Introduced by misalignment between emission scan and CT-derived attenuation maps.
AB  - Nonuniform soft-tissue attenuation affects the diagnostic accuracy of SPECT in
      myocardial perfusion imaging. The attenuation map required for attenuation
      correction can be acquired using x-ray tomography (CT). Frequent findings in
      attenuation-corrected images are defects in the apical and anterior myocardial
      wall. We assume that these are artifacts produced by misalignment of SPECT images
      and the attenuation map. METHODS: One hundred forty patients underwent myocardial
      perfusion imaging with 99mTc-methoxyisobutylisonitrile. Twenty-seven of 140
      showed pronounced defects in the apical or anterior wall only after CT-based
      attenuation correction. SPECT and corresponding CT slices were examined for
      misalignment in the ventrodorsal direction (y-direction) visually and by
      threshold-based delineation of the body surface. Mismatched studies were
      realigned and image reconstruction and analysis were redone. The effect of the
      correction was assessed visually and by semiquantitative analysis based on a 20
      segment model using 4D-MSPECT. RESULTS: In 15 of 27 patients, the improved
      coregistration led to smaller and less-pronounced defects in the regions
      mentioned. In 6 of 27 patients, former defects were judged as normal. No
      improvement was seen in only 4 patients. In these 4 subjects, the mismatch in the
      y-direction was <1 pixel (7 mm), and visual inspection suggested a coincident
      mismatch in the craniocaudal direction. In 2 cases, coregistration was not
      possible because the body outline extended beyond the CT field of view.
      Semiquantitative analysis revealed a significant increase of the relative uptake
      in the apex; in the apical segments of the anterior, septal, and inferior wall;
      and in the mid-anterior and mid-anteroseptal segment. Basal segments of the
      anterolateral, lateral, and inferolateral wall and the middle inferolateral
      segment showed a significant decrease of relative uptake. CONCLUSION:
      Misalignment in the y-direction between SPECT and the attenuation map can lead to
      artifacts in the apical, septal, and anterior wall, which will appear as defects.
      It also can cause overcorrection in the basal inferior and lateral segments.
      There is evidence that mismatches along the other directions may have a similar
      effect. The coregistration of SPECT and the attenuation map needs to be verified
      for every patient, even when using integrated dual-modality imaging devices.

PMID- 15471823
TI  - Electromechanical properties of perfusion/metabolism mismatch: comparison of
      nonfluoroscopic electroanatomic mapping with 18F-FDG PET.
AB  - The aim of this study was to compare nonfluoroscopic electroanatomic mapping
      (NOGA), SPECT perfusion imaging, and PET metabolic imaging for assessment of
      myocardial viability. In particular, we sought to elucidate differences of
      electromechanical properties between the perfusion/metabolism mismatch as an
      indicator of a potentially reversible ischemic injury and the
      perfusion/metabolism match indicating irreversibly damaged myocardial tissue.
      METHODS: Twenty-one patients with coronary artery disease underwent NOGA mapping
      of endocardial unipolar voltage, cardiac 18F-FDG PET of glucose utilization, and
      resting 201Tl SPECT of myocardial perfusion. RESULTS: Electrical activity was
      10.8 +/- 4.6 mV (mean +/- SD) in normal myocardium and was unchanged in
      hypoperfused segments with maintained glucose metabolism (perfusion/metabolism
      mismatch), 9.3 +/- 3.4 mV (P = not significant). In contrast, hypoperfused
      segments with a perfusion/metabolism match and nonviable segments showed
      significantly lower voltage (6.9 +/- 3.1 mV, P < 0.0001 and 4.1 +/- 1.1 mV, P <
      0.0001 vs. normal). In hypoperfused segments, metabolic activity was more closely
      related to endocardial voltage than was myocardial perfusion (201Tl vs. voltage:
      r = 0.38, SEE = 3.2, P < 0.001; 18F-FDG PET vs. voltage: r = 0.6, SEE = 2.8, P <
      0.0001). CONCLUSION: In hypoperfused myocardium, electrical activity by NOGA
      mapping is more closely related to PET metabolic activity than to SPECT
      myocardial perfusion. As NOGA mapping does not differentiate hypoperfused
      myocardium with enhanced glucose utilization from normal myocardium, results from
      NOGA mapping need to be correlated with results from perfusion imaging to
      identify hypoperfused, yet viable, myocardium and to stratify patients for
      revascularization procedures.

PMID- 15471825
TI  - Beta-adrenergic blockade and myocardial perfusion in coronary artery disease:
      differential effects in stenotic versus remote myocardial segments.
AB  - Beta-adrenergic blocking agents are widely used in coronary artery disease (CAD),
      although their impact on myocardial blood flow (MBF) and coronary flow reserve
      (CFR) remains unclear. We studied the effect of long-term beta-blocker treatment
      (carvedilol or metoprolol) on coronary microcirculation in CAD patients using
      PET. METHODS: Regional and global resting and adenosine-induced hyperemic MBF and
      CFR were measured with 13N-ammonia and PET in 36 CAD patients before and after 12
      wk of oral therapy with either carvedilol, 50 mg/d, or metoprolol, 100 mg/d.
      RESULTS: Beta-blockade decreased global resting MBF in proportion to cardiac work
      (from 0.86 +/- 0.20 to 0.77 +/- 0.14 mL/min/g, P < 0.05) without affecting global
      hyperemic flow. Hyperemic MBF was significantly lower in stenosis-dependent
      segments than in remote segments (1.76 +/- 0.64 vs. 2.04 +/- 0.67 mL/min/g, P <
      0.05) at baseline but was comparable in both after treatment (2.02 +/- 0.68 vs.
      1.90 +/- 0.78 mL/min/g, P = not statistically significant [NS]), resulting in a
      significant CFR increase in stenotic segments (+15%, P < 0.05) but not in remote
      segments (+9%, P = NS). CONCLUSION: The beneficial effect of beta-adrenergic
      blockade can be explained by the reduction in oxygen consumption (= decreased
      demand) but also by a modest improvement in vasodilator capacity (= increased
      supply). The improvement in CFR is found predominantly in stenosis-dependent
      rather than remote segments.

PMID- 15471827
TI  - PET/CT using 18F-FDG in suspected lung cancer recurrence: diagnostic value and
      impact on patient management.
AB  - The goal of this study was to assess the value of hybrid imaging using a combined
      PET/CT device with 18F-FDG in the diagnosis and clinical management of suspected
      recurrent lung cancer. METHODS: Forty-two patients with non-small cell lung
      cancer (NSCLC) with suspected recurrence due to new clinical, biochemical, and
      radiologic findings were prospectively evaluated. PET/CT results were compared
      with PET interpreted with side-by-side CT data. A final diagnosis of recurrence
      was confirmed by histologic tissue sampling during surgery or biopsy or by
      further clinical and radiologic work-up. The impact of PET/CT on patient
      management was assessed. RESULTS: Twenty-four of 27 positive PET/CT studies (89%)
      were proven to have recurrent disease. Fourteen of 15 negative PET/CT studies
      (93%) had no evidence of disease. The sensitivity, specificity, and positive and
      negative predictive values of PET/CT for diagnosis of recurrence were 96%, 82%,
      89%, and 93% compared with 96%, 53%, 75%, and 90%, respectively, for PET. PET/CT
      changed the PET lesion classification in 22 patients (52%), by determining the
      precise localization of sites of increased 18F-FDG uptake. PET/CT changed the
      management of 12 patients (29%) by eliminating previously planned diagnostic
      procedures (5 patients), by initiating a previously unplanned treatment option (4
      patients), or by inducing a change in the planned therapeutic approach (3
      patients). CONCLUSION: In patients with a suspected recurrence of NSCLC, PET/CT
      provides a better anatomic localization of suspicious lesions compared with PET
      interpreted with side-by-side CT data. This improved diagnostic performance of
      PET/CT has a further impact on the clinical management and treatment planning of
      the patients.

PMID- 15471826
TI  - Defining the priority of using 18F-FDG PET for recurrent cervical cancer.
AB  - PET with 18F-FDG has shown its potential in cervical cancer. For maximizing the
      benefits of this new imaging technology, we aimed to define the prognostic
      features of recurrent cervical cancer patients for selecting appropriate
      candidates using 18F-FDG PET. METHODS: Patients enrolled were from 2 independent
      prospective studies investigating the role of 18F-FDG PET in cervical cancer
      patients after definitive treatment with documented failure (CTRP-018) or
      unexplained elevated tumor marker serum levels (CTRP-016) and proven relapse
      after PET. A total of 55 eligible patients received PET and CT or MRI. Lesion
      status was determined from pathologic results or clinical follow-up. The benefits
      calculated were based on treatment that was modified because of the PET findings.
      The Cox proportional hazards ratio (HR) was used to select independent prognostic
      covariates. RESULTS: Thirty-six (65.5%) patients had treatment that was modified
      due to PET. Primary radiation (HR = 14.62; 95% confidence interval [CI] = 2.74
      77.92), squamous cell carcinoma antigen (SCC-Ag) > or = 4 ng/mL (HR = 5.82; 95%
      CI = 1.53-22.04), and presence of symptoms (HR = 6.24; 95% CI = 1.99-19.61) at
      recurrence were significant factors associated with poor survival. A scoring
      system using these covariates defined 3 distinct prognostic groups: score < or =
      1 (HR = 1.00); score = 2 (HR = 6.91; 95% CI = 1.49-32.14); and score = 3 (HR =
      60.46; 95% CI = 9.68-378.09) (P < 0.0001). CONCLUSION: Using this risk score, 18F
      FDG PET may offer maximal benefits by selecting appropriate recurrent cervical
      cancer patients for salvage therapy with precise restaging information.

PMID- 15471828
TI  - 99mTc-interleukin-2 scintigraphy as a potential tool for evaluating tumor
      infiltrating lymphocytes in melanoma lesions: a validation study.
AB  - Cutaneous melanoma is often characterized by the presence of tumor-infiltrating
      lymphocytes (TILs). The degree of such infiltration and cell activation are
      considered significant prognostic factors reflecting the host's immune response
      to the tumor; thus, patients with peritumoral infiltration may have a better
      prognosis and may also achieve a better response to interleukin-2 (IL2)
      immunotherapy. There is evidence that the expression of cluster designation (CD)
      25 antigen (IL2 receptor [IL2R]) is a good marker of activity of T lymphocytes
      against melanoma cells. The aim of this study was to evaluate in vivo the binding
      of 99mTc-IL2 to lymphocytes infiltrating cutaneous melanoma and to determine
      whether such uptake correlates with immunologic and histologic data, thus
      providing useful prognostic information for IL2 therapy in patients with advanced
      disease. METHODS: Thirty patients with cutaneous lesions suspected of being
      melanoma were studied. Planar gamma-camera images over known tumor sites were
      acquired 1 h after the injection of 111-185 MBq of 99mTc-IL2. Tumor uptake of
      99mTc-IL2 was measured as a target-to-background (T/B) radioactivity ratio. All
      patients underwent surgery, and histologic evaluation of the resected lesion was
      performed. The percentage of different peripheral blood lymphocyte subsets (CD3,
      CD4, CD8, CD16, CD25) and the percentage of IL2R-positive tumor cells on
      histologic sections were also measured. RESULTS: At final histology, 21 lesions
      were found to be melanoma and 9 were classified as benign. In 15 of 21 (71%)
      melanomas and 2 of 9 (22%) benign cutaneous lesions, we found uptake of 99mTc
      IL2. The calculated T/B ratios correlated significantly with the number of IL2R
      positive TILs. CONCLUSION: 99mTc-IL2 scintigraphy provides a means of in vivo
      measurement of the extent of tumor infiltration of IL2R-positive cells, thereby
      providing valuable prognostic information for selection of patients who may
      benefit from IL2 immunotherapy.

PMID- 15471829
TI  - 18F-FDG PET of gliomas at delayed intervals: improved distinction between tumor
      and normal gray matter.
AB  - We hypothesized that delineation of gliomas from gray matter with 18F-FDG PET
      could be improved by extending the interval between 18F-FDG administration and
      PET data acquisition. The purposes of this study were, first, to analyze standard
      and delayed 18F-FDG PET images visually and quantitatively to determine whether
      definition of tumor improved at later imaging times and, second, to investigate
      the dynamics of model-derived kinetic rate constants, particularly k4. METHODS:
      Nineteen adult patients with supratentorial gliomas were imaged from 0 to 90 min
      and once or twice later at 180-480 min after injection. In 15 patients, arterial
      sampling provided the early input function. Venous sampling provided the
      remaining curve to the end of the imaging sequence. Standardized uptake value
      (SUV) was calculated as tissue concentration of tracer per injected tracer dose
      per body weight. Ratios of tumor SUV relative to the SUV of gray matter, brain
      (including gray and white matter), or white matter were calculated at each
      imaging time point. Dynamic image data from tumor, gray matter, brain, or white
      matter were analyzed using a 2-compartment, 4-parameter model applied for the
      entire duration of imaging, in which delay, K1, distribution volume, k3, and k4
      were optimized using a nonlinear optimization method. Parameter estimation for
      each region included both an early subset of data from a conventional dynamic
      imaging period (0-60 min) and the full, extended dataset for each region.
      RESULTS: In 12 of the 19 patients, visual analysis showed that the delayed images
      better distinguished the high uptake in tumors relative to uptake in gray matter.
      SUV comparisons also showed greater uptake in the tumors than in gray matter,
      brain, or white matter at the delayed times. The estimated k4 values for tumors
      were not significantly different from those for gray matter in early imaging
      analysis but were lower (P < 0.01) using the extended-time data. CONCLUSION: The
      kinetic parameter results confirm the visual and SUV interpretation that tumor
      enhancement is greater than enhancement of surrounding brain regions at later
      imaging times, consistent with a greater effect of FDG-6-phosphate degradation on
      normal brain relative to glioma.

PMID- 15471830
TI  - Long-term efficacy of radionuclide therapy in patients with disseminated
      neuroendocrine tumors uncontrolled by conventional therapy.
AB  - Therapeutic options in patients with advanced-stage gastroenteropancreatic (GEP)
      neuroendocrine tumors are limited. We compared the efficacy of radionuclide
      therapy with 111In-pentetreotide and 131I-metaiodobenzylguanidine (MIBG) in 20
      patients (group A) with the outcome of similar patients who could not be treated
      for nonmedical reasons (group B, n = 12). The intent was to treat all patients
      because of uncontrolled tumor disease (n = 21), contraindication to chemotherapy
      or surgery (n = 7), or uncontrolled and badly tolerated clinical symptoms (n =
      4). METHODS: Group A patients received 3 monthly administrations of 3.7-7.4 GBq
      of 131I-MIBG (n = 5) or 7 GBq of 111In-pentetreotide (n = 15), according to the
      best tracer uptake. Clinical evaluation, biologic tests, and conventional imaging
      were performed at 3, 6, 12, 18, and 24 mo. Therapy was considered beneficial if
      clinical status improved, laboratory tests for secreting tumors improved by >20%,
      tumor progression was halted, the size of the most significant localization had
      decreased by >25%, and the dosage of analgesic and cold somatostatin therapy
      could be lowered. Pejorative events were defined as side effects due to therapy,
      relapse in clinical symptoms, tumor progression, tumor laboratory marker
      increase, and death. RESULTS: The overall survival rate at 3 mo was significantly
      higher in group A (P = 0.05). Radionuclide therapy was beneficial in 14 patients
      (73% of group A), with only 1 significant side effect. The average time before
      relapse was 16.1 +/- 7.8 mo. The overall Kaplan-Meier survival rate and
      cumulative progression-free and cumulative event-free survival rates during the
      first 15 mo were significantly higher in patients receiving radionuclide therapy
      (P = 0.019, P = 0.024, and P = 0.019, respectively). CONCLUSION: Radionuclide
      therapy is feasible and safe and significantly defers the occurrence of fatal and
      nonfatal events in patients clinically uncontrolled by conventional therapy.

PMID- 15471831
TI  - Clinical usefulness of 18F-FDG PET in nasopharyngeal carcinoma patients with
      questionable MRI findings for recurrence.
AB  - It has been reported that 18F-FDG PET is highly sensitive for the detection of
      recurrent head-and-neck cancer. The objective of our prospective study was to
      validate the ability of this technique to detect the presence of tumors in
      primary, nodal, and distant sites as well as to assess its overall clinical
      usefulness in patients with questionable MRI findings for residual or recurrent
      nasopharyngeal carcinoma (NPC). METHODS: From January 2002 to October 2003, a
      group of 37 NPC patients whose postradiation follow-up MRI examination showed
      questionable residual or recurrent disease was assessed with 18F-FDG PET. 18F-FDG
      PET was interpreted visually. Disease at primary, nodal, and distant sites was
      assessed. The final diagnosis was confirmed histopathologically or with clinical
      and imaging follow-up of at least 6 mo. RESULTS: Our results showed that the
      sensitivity and specificity of 18F-FDG PET for the detection of recurrent NPC
      were 91.6% and 76.0%, respectively, at the primary site; 90.0% and 88.9%,
      respectively, at nodal sites; and 100% and 90.6%, respectively, at distant sites.
      The overall sensitivity and specificity were 89.5% and 55.6%, respectively. Among
      the 37 patients, 18F-FDG PET added significant information to the MRI findings in
      18, including offering true-negative findings in 10, revealing unexpected small
      metastatic adenopathy in 3, and disclosing distant metastatic foci in 5.
      CONCLUSION: 18F-FDG PET is highly sensitive and moderately specific for the
      detection of recurrent NPC in patients with questionable MRI findings. Overall,
      18F-FDG PET appears to add significant information to MRI findings in about half
      of the NPC patients whose MRI examination shows questionable tumor recurrence.

PMID- 15471832
TI  - Is 18F-3'-fluoro-3'-deoxy-L-thymidine useful for the staging and restaging of non
      small cell lung cancer?
AB  - The objective of this study was to compare 18F-3'-fluoro-3'-deoxy-L-thymidine
      (FLT) PET with clinical TNM staging, including that by 18F-FDG PET, in patients
      with non-small cell lung cancer (NSCLC). METHODS: Patients with NSCLC underwent
      whole-body 18F-FDG PET and whole-body 18F-FLT PET, using a median of 360 MBq of
      18F-FDG (range, 160-500 MBq) and a median of 210 MBq of 18F-FLT (range, 130-420
      MBq). 18F-FDG PET was performed 90 min after 18F-FDG injection, and 18F-FLT PET
      was performed 60 min after 18F-FLT injection. Two viewers independently
      categorized the localization and intensity of tracer uptake for all lesions. All
      18F-FDG PET and 18F-FLT PET lesions were compared. Staging with 18F-FLT PET was
      compared with clinical TNM staging based on the findings of history, physical
      examination, bronchoscopy, CT, and 18F-FDG PET. From 8 patients, standardized
      uptake values (SUVs) were calculated. Maximal SUV and mean SUV were calculated.
      RESULTS: Sixteen patients with stage IB-IV NSCLC and 1 patient with strong
      suspicion of NSCLC were investigated. Sensitivity on a lesion-by-lesion basis was
      80% for the 8 patients who received treatment before 18F-FLT PET and 27% for the
      9 patients who did not receive pretreatment, using 18F-FDG PET as the reference
      standard. Compared with clinical TNM staging, staging by 18F-FLT PET was correct
      for 8 of 17 patients: 5 of 9 patients in the group with previous therapy and 3 of
      8 patients in the group without previous therapy. The maximal SUV of 18F-FLT PET,
      at a median of 2.7 and range of 0.8-4.5, was significantly lower than that of 18F
      FDG PET, which had a median of 8.0 and range of 3.7-18.8 (n = 8; P = 0.012). The
      mean SUV of 18F-FLT PET, at a median of 2.7 and range of 1.4-3.3, was
      significantly lower than that of 18F-FDG PET, which had a median of 6.2 and range
      of 2.8-13.9 (n = 6; P = 0.027). CONCLUSION: 18F-FLT PET is not useful for staging
      and restaging NSCLC.

PMID- 15471833
TI  - Radiation dosimetry of 99mTc-labeled C225 in patients with squamous cell
      carcinoma of the head and neck.
AB  - This study assessed the radiation dosimetry of 99mTc-labeled ethylene dicysteine
      (EC) C225 (EC-C225), a promising radioligand for functional tumor imaging.
      METHODS: Whole-body scanning was performed on 6 patients with head and neck
      squamous cell carcinoma up to 24 h after administration of 99mTc-EC-C225.
      Alternate patients who had been randomized to receive C225 in a phase III trial
      received 99mTc-EC-C225 before their 20-mg test dose or after their 400 mg/m2
      loading dose of unlabeled C225 (patients 1/3/5 and 2/4/6, respectively).
      Radiation dosimetry was assessed using the MIRD method. RESULTS: The critical
      organ was the kidney, with an average radiation-absorbed dose for all 6 patients
      of 0.0274 mGy/MBq. The average total-body absorbed dose was 0.0022 mGy/MBq (0.243
      cGy/1,110 MBq). CONCLUSION: The new radiopharmaceutical 99mTc-EC-C225 appears to
      have reasonable dosimetric properties for a diagnostic nuclear medicine agent.
      Correlation of the imaging results with clinical findings is the next step.

PMID- 15471834
TI  - 123I-FP-CIT SPECT imaging of dopamine transporters in patients with
      cerebrovascular disease and clinical diagnosis of vascular parkinsonism.
AB  - The purpose of our study was to prospectively evaluate the striatal uptake of
      123I-labeled N-(3-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane
      (FP-CIT) and the response to l-dopa therapy in patients with cerebrovascular
      disease (CVD) who develop clinical symptoms of vascular parkinsonism (VP).
      METHODS: Twenty consecutive patients who developed VP in the course of CVD were
      prospectively enrolled in the study. All patients had CT evidence of CVD (17
      patients had lacunar infarcts, 3 patients had territorial strokes). The clinical
      stage of the patients was assessed using the Hoehn and Yahr scale, and the
      severity of the symptoms was measured using the Unified Parkinson's Disease
      Rating Scale score. Ten age-matched subjects were used as controls. SPECT was
      performed 180 min after injection of 185 MBq 123I-FP-CIT using a dual-head gamma
      camera. The ratio of the mean specific-to-nonspecific striatal binding for the
      entire striatum, caudate, and putamen was calculated in all patients and compared
      with that of controls. Putamen-to-caudate binding ratios were compared as well.
      The response to therapy was compared between patients with normal and abnormal
      123I-FP-CIT binding. RESULTS: No correlation was found between any of the
      clinical variables and response to therapy in patients with VP. Nine patients had
      normal striatal 123I-FP-CIT binding with no significant differences in striatal
      or subregional binding ratios compared with those of the controls. In contrast,
      11 patients had significantly diminished striatal binding compared with that of
      controls (P < 0.001). Subanalyses showed significantly decreased binding in the
      caudate (P < 0.04 and P < 0.01 for the right and left caudate, respectively),
      diminished binding in the putamen (P < 0.04 and P < 0.01 for the right and left
      putamen, respectively), and a decreased putamen-to-caudate ratio on the right
      side (P < 0.001). The latter ratio was not significant on the left. Two of the 3
      patients with territorial strokes had significantly diminished striatal 123I-FP
      CIT binding in the hemisphere contralateral to the CT lesion. All 9 patients with
      normal scan findings had a poor response to L-dopa. Six of 11 patients with
      abnormal studies had no response to L-dopa, whereas 5 patients had a good
      response (P < 0.03). CONCLUSION: The diagnosis of VP cannot be accurately
      confirmed on the basis of clinical features alone because CVD may alter the
      typical presentation of PD. Functional imaging with 123I-FP-CIT is highly
      recommended in patients with CVD who develop symptoms of VP to confirm or exclude
      the existence of nigrostriatal dopaminergic degeneration. Identifying a subset of
      patients with reduced 123I-FP-CIT binding in the striatum is important for better
      treatment selection.

PMID- 15471835
TI  - Loss of dopamine transporter binding in Parkinson's disease follows a single
      exponential rather than linear decline.
AB  - Imaging of L-dopa uptake or dopamine transporter binding can monitor the
      progression of Parkinson's disease. Most follow-up studies have provided data
      best fitted by a linear decline of their outcome measure. However, in these
      studies, patients were repeatedly scanned during their first years after a
      diagnosis had been established. METHODS: We followed 6 patients with early
      Parkinson's disease for 7.5 y using 123I-labeled N-(3-iodopropene-2-yl)-2beta
      carbomethoxy-3beta-(4-chlorophenyl) tropane and SPECT. RESULTS: Loss of dopamine
      transporter binding was best fitted using a single exponential approximation. A
      63% loss (tau [time constant tau]) was calculated as 5.18 +/- 7.62 y in the
      putamen and 10.62 +/- 31.4 y in the caudate nucleus when a 3-parameter fit was
      used. CONCLUSION: These data approximate, for what is to our knowledge the first
      time, the decline of dopamine transporter binding as expected in biologic systems
      and may allow for models that correct for exponential decline to be developed and
      for disease-modifying effects in patients with advanced disease to be determined.

PMID- 15471836
TI  - Evaluation of early treatment response and predicting the need for colectomy in
      active ulcerative colitis with 99mTc-HMPAO white blood cell scintigraphy.
AB  - The rate of treatment failure in acute exacerbation of ulcerative colitis (UC)
      still reaches 20%-30%. Early identification of nonresponders to therapy is
      important, since intensified or other medical treatment or, ultimately, colectomy
      should be considered to reduce morbidity. Because 99mTc-hexamethylpropyleneamine
      oxime (99mTc-HMPAO) white blood cell (WBC) scintigraphy is accurate in
      determination of the severity and extent of UC lesions, the aim of this study was
      to assess whether WBC scintigraphy can predict early treatment failure in
      patients with an acute attack of UC. METHODS: We included 20 consecutive patients
      (7 women, 13 men; mean age +/- SEM, 36.8 +/- 10.9 y) with a history of UC who
      were hospitalized with severe exacerbations. All patients underwent endoscopy and
      scintigraphy within 24 h of admission and 1 wk after beginning treatment. WBCs
      were labeled with 200 MBq 99mTc-HMPAO. SPECT of the abdomen was performed 60 min
      after WBC reinjection. Maximum tracer uptake in the different colon segments was
      defined and expressed as a ratio of lumbar bone marrow uptake. The scintigraphic
      activity score (SAS) was expressed as the sum of segmental colon uptake ratios.
      Scintigraphic evolution was considered favorable when the SAS decreased by > or
      =50% and SPECT uptake ratios after therapy were < or =1.5 per segment.
      Rectosigmoidoscopy with biopsy was performed within 24 h after scintigraphy.
      RESULTS: Outcome analysis after 3 mo showed 6 of 20 patients in clinical and
      endoscopic or histologic (rectosigmoid) remission, without alteration of
      treatment (responders). Of the other patients (nonresponders), 5 of 14 received a
      colectomy, 5 of 14 received prolonged or intensified treatment, and 4 of 14
      received other treatment. In the responders group, the SAS (determined 1 wk after
      beginning therapy) significantly decreased in all patients. In the group of
      nonresponders, 10 patients had an increase of >10% in the SAS, 2 patients had an
      unchanged SAS, and 2 patients had a decreased SAS of >10% but had a residual mean
      segmental WBC uptake ratio of >1.5. There was a statistically significant
      difference between the responders and nonresponders (P < 0.01). CONCLUSION:
      Repeated 99mTc-HMPAO scintigraphy seems to be able to predict therapy resistance
      in UC within 1 wk after beginning treatment.

PMID- 15471837
TI  - Per-rectal portal scintigraphy is complementary to ultrasonography and endoscopy
      in the assessment of portal hypertension in children with chronic cholestasis.
AB  - We evaluated the clinical usefulness of 99mTc-pertechnetate per-rectal portal
      scintigraphy (PPS) in the assessment of portal circulation in children with
      chronic cholestasis. METHODS: PPS percentage shunt index (%SI) (the amount of
      radionuclide that shunts the liver and reaches the systemic blood after injection
      in the rectum) was measured in 22 children (mean age, 7.2 +/- 4.9 y) and compared
      with established clinical, laboratory, and endoscopic and imaging parameters of
      portal hypertension (PH). Fourteen children had surgically treated biliary
      atresia, and 8 had chronic intrahepatic cholestasis. Six clinically well children
      served as control subjects. RESULTS: The %SI was 14.3 +/- 3.1 and 34.7 +/- 18.8
      in controls and in patients, respectively (P < 0.01). A cutoff of 19% correctly
      allocated 100% of controls and 86% of patients. Mean %SI values were
      significantly higher in patients with biliary atresia, a high risk of
      pretransplantation death, esophageal varices (EV) at endoscopy, and an abnormal
      value for the ratio of lesser omentum thickness to abdominal aorta diameter
      (LO/Ao) at ultrasonography. Correlations between %SI values and several
      ultrasonographic continuous variables were statistically significant only for
      LO/Ao ratios (r = 0.51; P = 0.005) and spleen longitudinal diameters (r = 0.53; P
      = 0.01). The presence of EV could correctly be predicted only when values of %SI
      were greater than 30% (100% specificity; 56% sensitivity). Endoscopic and PPS
      findings agreed for a diagnosis of PH with EV in 3 of 7 patients with normal or
      borderline ultrasonographic LO/Ao ratios. PPS patterns and %SI values became
      normal in 3 children who underwent liver transplantation. CONCLUSION: In children
      with chronic cholestasis, PPS may be an advantageous, minimally invasive tool
      complementary to ultrasonography and endoscopy for better assessment and follow
      up of PH before and after liver transplantation.

PMID- 15471838
TI  - Regional cerebral blood flow in patients with mild hypothyroidism.
AB  - Emotional and cognitive abnormalities are common in adult hypothyroidism. Few
      studies, however, have evaluated cerebral perfusion and metabolism in this
      disorder. The aims of this study were to compare regional cerebral blood flow
      (rCBF) between hypothyroid patients and healthy subjects and assess flow during
      the euthyroid state after treatment. METHODS: Ten mildly hypothyroid patients,
      before and after thyroxine treatment, and 10 healthy controls underwent 99mTc
      hexamethylpropyleneamine oxime brain SPECT, MRI, and psychometric testing. SPECT
      images were analyzed using statistical parametric mapping. RESULTS: Compared with
      controls, rCBF in patients before treatment was lower in right parietooccipital
      gyri, cuneus, posterior cingulate, lingual gyrus, fusiform, insula, and pre- and
      postcentral gyri. Perfusion did not normalize on a return to the euthyroid state.
      CONCLUSION: Decreased rCBF in mild hypothyroidism is found in regions mediating
      attention, motor speed, memory, and visuospatial processing, faculties affected
      in hypothyroidism. Follow-up studies are needed to determine the longer-term
      persistence of perfusion abnormalities in this disorder.

PMID- 15471839
TI  - Increased cell death after therapy with an Arg-Gly-Asp-linked somatostatin
      analog.
AB  - Receptor-targeted scintigraphy and radionuclide therapy with radiolabeled
      somatostatin analogs are successfully applied for somatostatin receptor-positive
      tumors. The synergistic effects of an apoptosis-inducing factor, for example, the
      Arg-Gly-Asp (RGD) motif, can increase the radiotherapeutic efficacy of these
      peptides. Hence, the tumoricidal effects of the hybrid peptide RGD
      diethylaminetriaminepentaacetic acid (DTPA)-Tyr3-octreotate (cyclic[c](Arg-Gly
      Asp-D-Tyr-Asp)-Lys(DTPA)-D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr), hereafter
      referred to as RGD-DTPA-octreotate, were evaluated in comparison with those of
      RGD (c(Arg-Gly-Asp-D-Tyr-Asp)) and Tyr3-octreotate (D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr
      Cys)-Thr). METHODS: The therapeutic effects of RGD-111In-DTPA-octreotate, 111In
      DTPA-RGD, and 111In-DTPA-Tyr3-octreotate were investigated with various cell
      lines by use of a colony-forming assay, and caspase-3 activity was also
      determined. RESULTS: Tumoricidal effects were found with 111In-DTPA-RGD, 111In
      DTPA-Tyr3-octreotate, and RGD-111In-DTPA-octreotate, in order from least
      effective to most effective. Also, the largest increase in caspase-3 levels was
      found with RGD-111In-DTPA-octreotate. CONCLUSION: RGD-111In-DTPA-octreotate has
      more pronounced tumoricidal effects than 111In-DTPA-RGD and 111In-DTPA-Tyr3
      octreotate, because of increased apoptosis, as indicated by increased caspase-3
      activity.

PMID- 15471840
TI  - The additive value of combined assessment of myocardial perfusion and ventricular
      function studies.
AB  - In addition to providing quantitative ventricular function information, gated
      SPECT and radionuclide angiocardiographic studies can evaluate regional wall
      motion and ventricular volumes. This review focuses on the combined assessment of
      myocardial perfusion and left ventricular function. Two clear roles for nuclear
      imaging in clinical practice include the diagnosis of coronary artery disease and
      assessment of prognosis in patients with known coronary artery disease.
      Ventricular function information can help differentiate an attenuation artifact
      from an infarct and is helpful in diagnosing 3-vessel coronary disease.
      Additionally, several studies have highlighted the prognostic benefit to combined
      assessment of myocardial perfusion and ventricular function. Several new
      modalities have recently been reported that promise to continue to solidify the
      place of nuclear imaging in the diagnosis and prognosis of coronary artery
      disease.

PMID- 15471841
TI  - Bone marrow dosimetry using blood-based models for radiolabeled antibody therapy:
      a multiinstitutional comparison.
AB  - Standardization of marrow dosimetry is of considerable importance when estimating
      dose-response for a multicentered clinical trial involving radionuclide therapy.
      However, it is only within the past five years that the intercomparison of marrow
      dosimetry results among separate clinical trials that use the same agent has
      become scientifically feasible. In this work, we have analyzed reported marrow
      dosimetry results from radioimmunotherapy trials and recalculated marrow absorbed
      doses at a central facility using a standard blood model with patient-specific
      source data. The basic approach used in the American Association of Physicists in
      Medicine (AAPM)/Sgouros marrow dosimetry methodology was common to calculation
      performed at all participating institutions, including the central facility.
      Differences in dose estimates associated with starting assumptions and the exact
      implementation of the AAPM/Sgouros calculation methodology used by the source
      institutions and the central facility were quantified and compared. METHODS: Data
      from 22 patients enrolled in radiolabeled antibody clinical trials were randomly
      selected from 7 participating institutions for the assessment of marrow dose. The
      analysis was restricted to those patients who were treated with 131I- or 186Re
      labeled antibody and had no marrow involvement. Calculation of bone marrow dose
      at each participating institution was unique to the trial or institution, but all
      used some form of the AAPM/Sgouros blood model approach. The central facility
      adopted a marrow dosimetry model based on the AAPM/Sgouros model for radiolabeled
      antibodies using the standard MIRD approach to the remainder-of-body
      contribution. A standardized approach to account for variations in patient mass
      was used for the remainder-of-body component. To simplify clinical
      implementation, regional marrow uptake and time-dependent changes in the marrow
      to-blood concentration ratio were not included. Methods of formatting the
      collection of standard datasets useful in defining dose-response parameters are
      also presented. RESULTS: Bone marrow doses were calculated according to the
      method described for each of the 22 patients based on the patient-specific data
      supplied by the participating institutions. These values were then individually
      compared with the marrow doses originally reported by each institution.
      Comparison of the two calculation methods was expressed as a ratio of the marrow
      doses for each patient. The mean ratio for the dose estimates at the
      participating institution calculation compared with the central laboratory value
      was 0.920 +/- 0.259 (mean +/- SD), with a range from 0.708 to 1.202. CONCLUSION:
      The independent use of the AAPM/Sgouros method blood model approach to marrow
      dosimetry has brought these dose estimates to within 30% of the results obtained
      centrally compared with substantially higher uncertainties reported previously.
      Variations in calculation methodology or initial assumptions adopted by
      individual institutions may still contribute significant uncertainty to dose
      estimates, even when the same data are used as a starting point for the
      calculation comparison shown here. A clinically relevant, standard method for
      marrow dosimetry for radiolabeled antibodies is proposed as a benchmark for
      intercomparison purposes. A parameter sensitivity analysis and a summary
      discussion of the use of this model for potentially improving dose-response data
      correlation are also presented.

PMID- 15471842
TI  - Performance characteristics of a newly developed PET/CT scanner using NEMA
      standards in 2D and 3D modes.
AB  - This study evaluates the 2-dimensional (2D) and 3-dimensional (3D) performance
      characteristics of a newly developed PET/CT scanner using the National Electrical
      Manufacturers Association (NEMA) NU 2-1994 (NU94) and NEMA NU 2-2001 (NU01)
      standards. The PET detector array consists of 10,080 individual bismuth germanate
      crystals arranged in 24 rings of 420 crystals each. The size of each crystal is
      6.3 x 6.3 x 30 mm in the axial, transaxial, and radial dimensions, respectively.
      The PET detector ring diameter is 88.6 cm with axial and transaxial fields of
      view (FOVs) of 15.7 and 70 cm, respectively. The scanner has a uniform patient
      port of 70 cm throughout the PET and CT FOV, and the PET scanner is equipped with
      retractable septa to allow 2D and 3D imaging. METHODS: Spatial resolution,
      scatter fraction, sensitivity, counting rate, image quality, and accuracy as
      defined by the NEMA protocols of NU94 and NU01 for 2D and 3D modes are evaluated.
      The 2D mode data were acquired with a maximum ring difference of 5, whereas the
      3D mode acquisition used ring differences of 23. Both 2D and 3D mode data were
      acquired with an energy window of 375-650 keV. Random estimation from singles
      counting rate was applied to all relevant analysis. In addition, images from 2
      clinical whole-body oncology studies acquired in 2D and 3D modes are shown to
      demonstrate the image quality obtained from this scanner. RESULTS: The 2D NU94
      transaxial resolution is 6.1-mm full width at half maximum (FWHM) 1 cm off center
      and increases to 6.9 mm tangential and 8.1 mm radial at a radius (R) of 20 cm.
      NU01 2D average transaxial (axial) FWHM resolution measured 6.1 (5.2) mm at R = 1
      cm and 6.7 (6.1) mm at R = 10 cm. The NU94 scatter fraction for 2D (3D) was 13%
      (29%), whereas the NU01 scatter fraction gave 19% (45%). NU01 peak 2D (3D) noise
      equivalent counting rate (T(2)/[T + R + S]) was 90.2 (67.8) kilocount per second
      (kcps) at 52.5 (12) kBq/mL. Total 2D (3D) system sensitivity for true events is 8
      (32.9) kcps/kBq/mL for NU94 and 1.95 (9.2) kcps/Bq for NU01. CONCLUSION: The
      results show excellent system sensitivity with relatively uniform resolution
      throughout the FOV, making this scanner highly suitable for whole-body studies.

PMID- 15471843
TI  - Coexpression of herpesviral thymidine kinase reporter gene and VEGF gene for
      noninvasive monitoring of therapeutic gene transfer: an in vitro evaluation.
AB  - Coexpression of a reporter gene and a therapeutic gene may allow for noninvasive
      monitoring of cardiac gene therapy. We sought to evaluate the usefulness of an
      adenoviral vector expressing mutant herpesviral thymidine kinase reporter gene
      (HSV1-sr39tk) and vascular endothelial growth factor (VEGF) 121 in independent
      expression cassettes (Ad4tk). METHODS: Accumulation of 14C-2'-fluoro-5-methyl-1
      beta-D-arabinofuranosyluracil (FIAU) and 9-(4-18F-fluoro-3
      hydroxymethylbutyl)guanine (FHBG) as reporter probes, and secretion of VEGF into
      medium, were determined for Ad4tk-infected H9c2 rat cardiac cells in vitro.
      RESULTS: In vitro tracer uptake increased with increasing vector concentration
      and over time. It was comparable to cells infected with adenovirus expressing
      only wild-type HSV1-tk (reporter probe: 14C-FIAU) or mutant HSV1-sr39tk (reporter
      probe: 18F-FHBG). No significant uptake was observed in cells infected with
      adenovirus expressing VEGF alone. With increasing vector concentration, Ad4tk
      infected cells increasingly released VEGF into medium. VEGF production correlated
      significantly with cellular reporter probe uptake (r = 0.93; P = 0.0003).
      CONCLUSION: The usefulness of a vector coexpressing HSV1-tk and VEGF for
      noninvasive imaging of expression of a therapeutic transgene has been
      demonstrated in vitro. This approach may allow for future in vivo monitoring of
      cardiac angiogenesis gene therapy.

PMID- 15471844
TI  - Scintigraphic detection of pulmonary aspergillosis in rabbits with a radiolabeled
      leukotriene b4 antagonist.
AB  - Radiolabeled chemotactic peptides have been studied for their applicability to
      the visualization of infectious and inflammatory foci. Because a radiolabeled
      leukotriene B4 (LTB4) antagonist allowed visualization of intramuscular E. coli
      abscesses in rabbits within a few hours after injection, we decided to test the
      imaging characteristics of this agent in a more clinically relevant model of
      pulmonary aspergillosis. The pharmacokinetics and imaging characteristics of the
      111In-labeled LTB4 antagonist DPC11870 were studied in New Zealand White rabbits
      with experimental pulmonary aspergillosis infection. The imaging characteristics
      of 111In-DPC11870 were compared with those of 67Ga-citrate, a radiopharmaceutical
      commonly used to detect pulmonary infections in patients. METHODS: Pulmonary
      aspergillosis was induced in the left lung of rabbits by intratracheal
      inoculation of 1 x 10(8) conidia of Aspergillus fumigatus. Three days after the
      inoculation, the rabbits received 111In-DPC11870 or 67Ga-citrate intravenously.
      Images were acquired at several time points up to 24 h after injection. RESULTS:
      Pulmonary aspergillosis was visualized with both agents. Images acquired after
      injection of 111In-DPC11870 showed uptake in the pulmonary lesions from 6 h after
      injection. Because of accumulation at the site of infection and clearance from
      the background, the images improved with time. Region-of-interest analysis at 24
      h after injection revealed infected lung-to-normal lung ratios of 5.0 +/- 1.5 for
      111In-DPC11870 and 2.9 +/- 0.6 for 67Ga-citrate. CONCLUSION: The radiolabeled
      LTB4 antagonist DPC11870 clearly delineated experimentally induced pulmonary
      aspergillosis in rabbits. Images acquired at 24 h after injection of 111In
      DPC11870 were superior to those obtained after injection of 67Ga-citrate.

PMID- 15471845
TI  - Evaluation of 3'-deoxy-3'-18F-fluorothymidine for monitoring tumor response to
      radiotherapy and photodynamic therapy in mice.
AB  - 3'-Deoxy-3'-18F-fluorothymidine (18F-FLT) has been suggested as a new PET tracer
      for imaging tumor proliferation. We investigated the use of 18F-FLT to monitor
      the response of tumors to radiotherapy and photodynamic therapy (PDT) in mice.
      METHODS: C3H/He mice bearing an SCCVII tumor were treated with single-dose x-ray
      irradiation of 20 Gy. Tumor uptake was examined for 18F-FLT, 3H-thymidine (3H
      Thd), 18F-FDG, and 14C-deoxyglucose (14C-DG) at 6 h, 12 h, 24 h, 3 d, and 7 d
      after radiotherapy. BALB/c nu/nu mice bearing a HeLa tumor were treated with PDT.
      Tumor uptake was examined for the 4 tracers at 24 h after PDT. Expression of
      proliferating cell nuclear antigen (PCNA) was determined in untreated and treated
      tumors. RESULTS: In the biodistribution study, considerable uptake of 18F-FLT was
      observed in both tumor types. Tumor volumes decreased to 39.3% +/- 22.4% at 7 d
      after radiotherapy. The PCNA labeling index was reduced in x-ray-irradiated
      tumors (control, 53.2% +/- 8.7%; 6 h, 38.5% +/- 5.3%; 24 h after radiotherapy,
      36.8% +/- 5.3%). 18F-FLT uptake in tumor expressed as the percentage of the
      injected dose per gram of tumor (%ID/g) decreased significantly at 6 h and
      remained low until 3 d after radiotherapy (control, 9.7 +/- 1.2 %ID/g; 6 h, 5.9
      +/- 0.4 %ID/g; 24 h, 6.1 +/- 1.3 %ID/g; 3 d after radiotherapy, 6.4 +/- 1.1
      %ID/g). 18F-FDG uptake tended to gradually decrease but a significant decrease
      was found only at 3 d (control, 12.1 +/- 2.7 %ID/g; 6 h, 13.3 +/- 2.3 %ID/g; 24
      h, 8.6 +/- 1.8 %ID/g; 3 d after radiotherapy, 6.9 +/- 1.2 %ID/g). PDT resulted in
      a reduction of the PCNA labeling index (control, 82.0% +/- 8.6%; 24 h after PDT,
      13.5% +/- 12.7%). Tumor uptake of 18F-FLT decreased (control, 11.1 +/- 1.3 %ID/g;
      24 h after PDT, 4.0 +/- 2.2 %ID/g), whereas 18F-FDG uptake did not decrease
      significantly after PDT (control, 3.5 +/- 0.6 %ID/g; 24 h after PDT, 2.3 +/- 1.1
      %ID/g). Changes in the uptake of 18F-FLT and 18F-FDG were similar to those of 3H
      Thd and 14C-DG, respectively. CONCLUSION: In our model system, changes in 18F-FLT
      uptake after radiotherapy and PDT were correlated with those of 3H-Thd and the
      PCNA labeling index. The decrease in 18F-FLT uptake after treatments was more
      rapid or pronounced than that of 18F-FDG. Therefore, 18F-FLT may be a feasible
      PET tracer for monitoring response to therapy in oncology.

PMID- 15471846
TI  - In vivo evaluation of 111In-labeled T-lymphocyte homing in experimental colitis.
AB  - Blockade of lymphocyte recruitment to the intestinal mucosa is considered a
      useful therapy for inflammatory bowel disease (IBD) and anti-alpha4 antibodies
      have clinical benefit in patients with active Crohn's disease. The aim of this
      study was to evaluate a scintigraphic technique to assess lymphocyte homing to
      the colon in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental
      colitis (TNBS colitis) in vivo. METHODS: TNBS-sensitized and nonsensitized murine
      total lymphocytes or CD4+ lymphocytes were radiolabeled with 111In-oxinate. Cells
      were injected into control mice (n = 5) or mice with TNBS colitis (n = 5).
      Specific abdominal radioactive uptake was determined by SPECT using a dedicated
      pinhole system 48 h after cell transfer. Radioactive colon uptake was correlated
      with histology and colon weight as parameters of inflammation. RESULTS: The
      radioactive colon uptake was most evident in mice with TNBS colitis that received
      sensitized lymphocytes (uptake ratio [mean +/- SEM], 0.51 +/- 0.03 vs. 0.22 +/-
      0.04; P = 0.004). The sensitized 111In-labeled lymphocytes exacerbated colitis
      compared with nonsensitized lymphocytes. The colon uptake correlated well with
      both colon weight and histologic score (R2 = 0.836 and 0.933, respectively). The
      use of purified 111In labeled CD4+ lymphocytes resulted in a similar
      scintigraphic pattern. Administration of an anti-alpha4 antibody decreased
      radioactivity colon uptake of the (111)In-labeled cells compared with the control
      antibody in mice with TNBS colitis (uptake ratio, 0.72 +/- 0.14 to 0.33 +/- 0.03;
      P = 0.012). CONCLUSION: Animal pinhole SPECT can be applied for temporal and
      spatial analysis of the lymphocyte homing process in experimental colitis. This
      technique makes possible the in vivo evaluation of therapeutic efficacy of new
      drugs that interfere with lymphocyte migration. Moreover, colon uptake of
      radioactivity can be used as a parameter of disease activity in experimental
      colitis.

PMID- 15471847
TI  - Imaging endogenous gene expression in brain cancer in vivo with 111In-peptide
      nucleic acid antisense radiopharmaceuticals and brain drug-targeting technology.
AB  - Imaging endogenous gene expression with sequence-specific antisense
      radiopharmaceuticals is possible if the antisense agent is enabled to traverse
      the biologic membrane barriers that separate the blood compartment from messenger
      RNA (mRNA) molecules in the cytoplasm of the target cell. The present studies
      were designed to image endogenous gene expression in brain cancer using peptide
      nucleic acid (PNA) antisense agents that were modified to allow for (a) chelation
      of the 111In radionuclide and (b) attachment to a brain targeting system, which
      delivers the PNA across both the blood-brain barrier (BBB) and the tumor cell
      membrane. METHODS: PNAs were designed that were antisense to either the rat glial
      fibrillary acidic protein (GFAP) mRNA or the rat caveolin-1alpha (CAV) mRNA. The
      PNA contained an amino-terminal diethylenetriaminepentaacetic acid moiety to
      chelate 111In and a carboxyl-terminal epsilon-biotinyl lysine residue, which
      enabled attachment to the delivery system. The latter comprised streptavidin (SA)
      and the murine OX26 monoclonal antibody to the rat transferrin receptor (TfR),
      which were joined by a thiol-ether linker. Control PNAs were not conjugated to SA
      OX26. Brain tumors developed after the intracerebral injection of rat RG2 glial
      cells in adult Fischer CD344 rats. GFAP and CAV gene expression in the tumor in
      vivo was monitored by confocal microscopy and Northern blotting with GFAP and CAV
      complementary DNAs. RESULTS: If the PNA was not targeted to the TfR, then no
      imaging of any brain structures was possible, owing to the absence of PNA
      transport across the BBB. Conjugation of the 111In-GFAP-PNA to the SA-OX26
      delivery system did not image brain cancer, owing to the downregulation of the
      GFAP mRNA in brain glial tumors. In contrast, brain cancer was selectively imaged
      with the 111In-CAV-PNA conjugated to SA-OX26 owing to upregulation of CAV gene
      expression in brain cancer. CONCLUSION: Imaging endogenous gene expression in
      vivo with PNA antisense radiopharmaceuticals is possible if drug-targeting
      technology is used. Attachment of the PNA antisense agent to the targeting ligand
      enables the antisense radiopharmaceutical to traverse biologic membrane barriers
      and access intracellular target mRNA molecules.

PMID- 15471848
TI  - Pegylated Arg-Gly-Asp peptide: 64Cu labeling and PET imaging of brain tumor
      alphavbeta3-integrin expression.
AB  - The alphav-integrins, cell adhesion molecules that are highly expressed on
      activated endothelial cells and tumor cells but not on dormant endothelial cells
      or normal cells, present an attractive target for tumor imaging and therapy. We
      previously coupled a cyclic Arg-Gly-Asp (RGD) peptide, c(RGDyK), with 1,4,7,10
      tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) and labeled the RGD
      DOTA conjugate with 64Cu (half-life, 12.8 h; 19% beta+) for solid tumor
      targeting, with high tumor-to-background contrast. The rapid tumor washout rate
      and persistent liver and kidney retention of this tracer prompted us to optimize
      the tracer for improved pharmacokinetic behavior. In this study, we introduced a
      polyethylene glycol (PEG; molecular weight, 3,400) moiety between DOTA and RGD
      and evaluated the 64Cu-DOTA-PEG-RGD tracer for microPET imaging in brain tumor
      models. METHODS: DOTA was activated in situ and conjugated with RGD-PEG-NH2 under
      slightly basic conditions. alphavbeta3-Integrin-binding affinity was evaluated
      with a solid-phase receptor-binding assay in the presence of 125I-echistatin.
      Female nude mice bearing subcutaneous U87MG glioblastoma xenografts were
      administered 64Cu-DOTA-PEG-RGD, and the biodistributions of the radiotracer were
      evaluated from 30 min to 4 h after injection. microPET (20 min of static imaging
      at 1 h after injection) and then quantitative autoradiography were used for tumor
      visualization and quantification. The same tracer was also applied to an
      orthotopic U87MG model for tumor detection. RESULTS: The radiotracer was
      synthesized with a high specific activity (14,800-29,600 GBq/mmol [400-800
      Ci/mmol]). The c(RGDyK)-PEG-DOTA ligand showed intermediate binding affinity for
      alphavbeta3-integrin (50% inhibitory concentration, 67.5 +/- 7.8 nmol/L [mean +/-
      SD]). The pegylated RGD peptide demonstrated rapid blood clearance (0.57 +/- 0.15
      percentage injected dose [%ID]/g [mean +/- SD] at 30 min after injection and 0.03
      +/- 0.02 %ID/g at 4 h after injection). Activity accumulation in the tumor was
      rapid and high at early time points (2.74 +/- 0.45 %ID/g at 30 min after
      injection), and some activity washout was seen over time (1.62 +/- 0.18 %ID/g at
      4 h after injection). Compared with (64)Cu-DOTA-RGD, this tracer showed improved
      in vivo kinetics, with significantly reduced liver uptake (0.99 +/- 0.08 %ID/g
      vs. 1.73 +/- 0.39 %ID/g at 30 min after injection and 0.58 +/- 0.07 %ID/g vs.
      2.57 +/- 0.49 %ID/g at 4 h after injection). The pegylated RGD peptide showed
      higher renal accumulation at early time points (3.51 +/- 0.24 %ID/g vs. 2.18 +/-
      0.23 %ID/g at 30 min after infection) but more rapid clearance (1.82 +/- 0.29
      %ID/g vs. 2.01 +/- 0.25 %ID/g at 1 h after injection) than 64Cu-DOTA-RGD. The
      integrin receptor specificity of this radiotracer was demonstrated by blocking of
      tumor uptake by coinjection with nonradiolabeled c(RGDyK). The high tumor-to
      organ ratios for the pegylated RGD peptide tracer (at 1 h after injection: tumor
      to-blood ratio, 20; tumor-to-muscle ratio, 12; tumor-to-liver ratio, 2.7; and
      tumor-to-kidney ratio, 1.2) were confirmed by microPET and autoradiographic
      imaging in a subcutaneous U87MG tumor model. This tracer was also able to detect
      an orthotopic brain tumor in a model in which U87MG cells were implanted into the
      mouse forebrain. Although the magnitude of tumor uptake in the orthotopic
      xenograft was lower than that in the subcutaneous xenograft, the orthotopic tumor
      was still visualized with clear contrast from normal brain tissue. CONCLUSION:
      This study demonstrated the suitability of a PEG moiety for improving the in vivo
      kinetics of a 64Cu-RGD peptide tracer without compromising the tumor-targeting
      ability and specificity of the peptide. Systematic investigations of the effects
      of the size and geometry of PEG on tumor targeting and in vivo kinetics will lead
      to the development of radiotracers suitable for clinical applications such as
      visualizing and quantifying alphav-integrin expression by PET. In addition, the
      same ligand labeled with therapeutic radionuclides may be applicable for integrin
      targeted internal radiotherapy.

PMID- 15471849
TI  - 131I-rituximab: relationship between immunoreactivity and specific activity.
AB  - As part of a search for optimal conditions for radioimmunotherapy of lymphoma,
      rituximab was labeled with 2 different specific activities of 131I and
      immunoreactivity was comparatively measured. METHODS: Labeling was performed with
      chloramine T using as starting conditions 185 MBq of 131I per 1 mg and per 5 mg
      of antibody for labelings A and B, respectively. Six comparative labelings were
      performed over a period of 10 mo with similar efficacy and purified by anion
      exchange chromatography. Immunoreactivity was determined immediately after
      labeling in parallel assays using different concentrations of fresh Raji and
      Daudi cells. Results were compared at maximal observed specific binding on 10(7)
      cells and after extrapolation to infinite antigen excess. A statistical analysis
      was performed to predict the frequency of radiolabeled mono- and polyiodinated
      antibodies: First, a gaussian distribution predicted the number of iodine atoms
      per antibody in labelings A and B, respectively; then, the radiolabeling
      probability was developed according to the Newton binome. RESULTS: Final
      radiochemical purity was >98.4% for all labelings. The final mean specific
      activities were 169.7 MBq/mg and 32.8 MBq/mg, corresponding to 0.87 and 0.17
      iodine atoms per antibody in labelings A and B, respectively. Labeling B showed a
      significantly higher immunoreactivity than did labeling A, the mean relative
      increase in binding being > or =28% for both Raji cells and Daudi cells. The
      predictive statistical analysis indicated that 57.3% and 15.4% of radiolabeled
      antibodies in labelings A and B, respectively, were polyiodinated. CONCLUSION:
      The low specific activity of 131I-rituximab allowed preservation of a high
      immunoreactivity and correlated with the prediction of a low percentage of
      polyiodinated radiolabeled antibodies.

PMID- 15471850
TI  - Role of cyclooxygenase-2 in cytokine-induced beta-cell dysfunction and damage by
      isolated rat and human islets.
AB  - Type I diabetes mellitus is an autoimmune disease characterized by the selective
      destruction of the insulin-secreting beta-cell found in pancreatic islets of
      Langerhans. Cytokines such as interleukin-1 (IL-1), interferon-gamma (IFN-gamma),
      and tumor necrosis factor-alpha (TNF-alpha) mediate beta-cell dysfunction and
      islet degeneration, in part, through the induction of the inducible isoform of
      nitric-oxide synthase and the production of nitric oxide by beta-cells. Cytokines
      also stimulate the expression of the inducible isoform of cyclooxygenase, COX-2,
      and the production of prostaglandin E(2) (PGE(2)) by rat and human islets;
      however, the role of increased COX-2 expression and PGE(2) production in
      mediating cytokine-induced inhibition of islet metabolic function and viability
      has been incompletely characterized. In this study, we have shown that treatment
      of rat islets with IL-1beta or human islets with a cytokine mixture containing IL
      1beta + IFN-gamma +/- TNF-alpha stimulates COX-2 expression and PGE(2) formation
      in a time-dependent manner. Co-incubation of rat and human islets with selective
      COX-2 inhibitors SC-58236 and Celecoxib, respectively, attenuated cytokine
      induced PGE(2) formation. However, these inhibitors failed to prevent cytokine
      mediated inhibition of insulin secretion or islet degeneration. These findings
      indicate that selective inhibition of COX-2 activity does not protect rat and
      human islets from cytokine-induced beta-cell dysfunction and islet degeneration
      and, furthermore, that islet production of PGE(2) does not mediate these
      inhibitory and destructive effects.

PMID- 15471851
TI  - Identification and characterization of PS-GAP as a novel regulator of caspase
      activated PAK-2.
AB  - p21-activated protein kinase (PAK)-2 is a member of the PAK family of
      serine/threonine kinases. PAKs are activated by the p21 G-proteins Rac and Cdc42
      in response to a variety of extracellular signals and act in pathways controlling
      cell growth, shape, motility, survival, and death. PAK-2 is unique among the PAK
      family members because it is also activated through proteolytic cleavage by
      caspase-3 or similar proteases to generate the constitutively active PAK-2p34
      fragment. Activation of full-length PAK-2 by Rac or Cdc42 stimulates cell
      survival and protects cells from cell death, whereas caspase-activated PAK-2p34
      induces a cell death response. Caspase-activated PAK-2p34 is rapidly degraded by
      the 26 S proteasome, but full-length PAK-2 is not. Stabilization of PAK-2p34 by
      preventing its polyubiquitination and degradation results in a dramatic
      stimulation of cell death. Although many proteins have been shown to interact
      with and regulate full-length PAK-2, little is known about the regulation of
      caspase-activated PAK-2p34. Here, we identify PS-GAP as a regulator of caspase
      activated PAK-2p34. PS-GAP is a GTPase-activating protein for Cdc42 and RhoA that
      was originally identified by its interaction with the tyrosine kinase PYK-2. PS
      GAP interacts specifically with caspase-activated PAK-2p34, but not active or
      inactive full-length PAK-2, through a region between the GAP and SH3 domains. The
      interaction with PS-GAP inhibits the protein kinase activity of PAK-2p34 and
      changes the localization of PAK-2p34 from the nucleus to the perinuclear region.
      Furthermore, PS-GAP decreases the stimulation of cell death induced by
      stabilization of PAK-2p34.

PMID- 15471852
TI  - Interaction between protein kinase Cmu and the vanilloid receptor type 1.
AB  - The capsaicin receptor VR1 is a polymodal nociceptor activated by multiple
      stimuli. It has been reported that protein kinase C plays a role in the
      sensitization of VR1. Protein kinase D/PKCmu is a member of the protein kinase D
      serine/threonine kinase family that exhibits structural, enzymological, and
      regulatory features distinct from those of the PKCs, with which they are related.
      As part of our effort to optimize conditions for evaluating VR1 pharmacology, we
      found that treatment of Chinese hamster ovary (CHO) cells heterologously
      expressing rat VR1 (CHO/rVR1) with butyrate enhanced rVR1 expression and
      activity. The expression of PKCmu and PKCbeta1, but not of other PKC isoforms,
      was also enhanced by butyrate treatment, suggesting the possibility that these
      two isoforms might contribute to the enhanced activity of rVR1. In support of
      this hypothesis, we found the following. 1) Overexpression of PKCmu enhanced the
      response of rVR1 to capsaicin and low pH, and expression of a dominant negative
      variant of PKCmu reduced the response of rVR1. 2) Reduction of endogenous PKCmu
      using antisense oligonucleotides decreased the response of exogenous rVR1
      expressed in CHO cells as well as of endogenous rVR1 in dorsal root ganglion
      neurons. 3) PKCmu localized to the plasma membrane when overexpressed in CHO/rVR1
      cells. 4) PKCmu directly bound to rVR1 expressed in CHO cells as well as to
      endogenous rVR1 in dorsal root ganglia or to an N-terminal fragment of rVR1,
      indicating a direct interaction between PKCmu and rVR1. 5) PKCmu directly
      phosphorylated rVR1 or a longer N-terminal fragment (amino acids 1-118) of rVR1
      but not a shorter one (amino acids 1-99). 6) Mutation of S116A in rVR1 blocked
      both the phosphorylation of rVR1 by PKCmu and the enhancement by PKCmu of the
      rVR1 response to capsaicin. We conclude that PKCmu functions as a direct
      modulator of rVR1.

PMID- 15471853
TI  - Five histidine kinases perceive osmotic stress and regulate distinct sets of
      genes in Synechocystis.
AB  - Microorganisms respond to hyperosmotic stress via changes in the levels of
      expression of large numbers of genes. Such responses are essential for
      acclimation to a new osmotic environment. To identify factors involved in the
      perception and transduction of signals caused by hyperosmotic stress, we examined
      the response of Synechocystis sp. PCC 6803, which has proven to be a particularly
      useful microorganism in similar analyses. We screened knockout libraries of
      histidine kinases (Hiks) and response regulators (Rres) in Synechocystis by DNA
      microarray and slot-blot hybridization analyses, and we identified several two
      component systems, which we designated Hik-Rre systems, namely, Hik33-Rre31,
      Hik34-Rre1, and Hik10-Rre3, as well as Hik16-Hik41-Rre17, as the transducers of
      hyperosmotic stress. We also identified Hik2-Rre1 as a putative additional two
      component system. Each individual two-component system regulated the
      transcription of a specific group of genes that were responsive to hyperosmotic
      stress.

PMID- 15471854
TI  - MUC1 membrane trafficking is modulated by multiple interactions.
AB  - MUC1 is a mucin-like transmembrane protein found on the apical surface of many
      epithelia. Because aberrant intracellular localization of MUC1 in tumor cells
      correlates with an aggressive tumor and a poor prognosis for the patient,
      experiments were designed to characterize the features that modulate MUC1
      membrane trafficking. By following [(35)S]Met/Cys-labeled MUC1 in glycosylation
      defective Chinese hamster ovary cells, we found previously that truncation of O
      glycans on MUC1 inhibited its surface expression and stimulated its
      internalization by clathrin-mediated endocytosis. To identify signals for MUC1
      internalization that are independent of its glycosylation state, the ectodomain
      of MUC1 was replaced with that of Tac, and chimera endocytosis was measured by
      the same protocol. Endocytosis of the chimera was significantly faster than for
      MUC1, indicating that features of the highly extended ectodomain inhibit MUC1
      internalization. Analysis of truncation mutants and tyrosine mutants showed that
      Tyr(20) and Tyr(60) were both required for efficient endocytosis. Mutation of
      Tyr(20) significantly blocked coimmunoprecipitation of the chimera with AP-2,
      indicating that Y(20)HPM is recognized as a YXXphi motif by the mu2 subunit. The
      tyrosine-phosphorylated Y(60)TNP was previously identified as an SH2 site for
      Grb2 binding, and we found that mutation of Tyr(60) blocked coimmunoprecipitation
      of the chimera with Grb2. This is the first indication that Grb2 plays a
      significant role in the endocytosis of MUC1.

PMID- 15471856
TI  - Misfolding of major histocompatibility complex class I molecules in activated T
      cells allows cis-interactions with receptors and signaling molecules and is
      associated with tyrosine phosphorylation.
AB  - Knowledge of the origin and biochemical status of beta(2)-microglobulin-free or
      misfolded major histocompatibility complex (MHC)-I molecules is essential for
      understanding their pleiotropic properties. Here we show that in normal human T
      cells, misfolding of MHC-I molecules is turned on upon activation and cell
      division and is proportional to the level of proliferation. Immunoprecipitation
      showed that a number of proteins are associated with MHC-I heavy chains at the
      surface of activated T cells, including the CD8alphabeta receptor and the
      chaperone tandem calreticulin/ERp57, associations that rely upon the existence of
      a pool of HC-10-reactive molecules. Biochemical analysis showed that misfolded
      MHC-I molecules present at the cell surface are fully glycosylated mature
      molecules. Importantly, misfolded MHC-I molecules are tyrosine phosphorylated and
      are associated with kinase activity. In vitro kinase assays followed by
      reprecipitation indicated that tyrosine phosphorylation of the class I heavy
      chain is probably mediated by a Src tyrosine kinase because Lck was found
      associated with HC-10 immunocomplexes. Finally, we show that inhibition of
      tyrosine phosphorylation by using the Src-family tyrosine kinase inhibitor PP2
      resulted in enhanced release of MHC-I heavy chains from the cell surface of
      activated T cells and a slight down-regulation of cell surface W6/32-reactive
      molecules. This study provides new insights into the biology of MHC-I molecules
      and suggests that tyrosine phosphorylation may be involved in the regulation of
      MHC-I misfolding and expression.

PMID- 15471855
TI  - Role of pim-1 in smooth muscle cell proliferation.
AB  - The proliferation of vascular smooth muscle cells (VSMCs) and alterations of
      their phenotype are implicated in the pathogenesis of atherosclerosis. Arterial
      wall injury induces the expression of proto-oncogenes, leading to the
      proliferation of VSMCs. In particular, c-Myc and c-Myb play a central role in
      cell cycle progression and are essential for VSMC replication. The protooncogene
      Pim-1 cooperates with c-Myc and enhances the transcriptional activity of c-Myb in
      hematopoietic cells, suggesting that Pim-1 is involved in cell cycle regulation.
      The aim of this study was to examine the possible involvement of Pim-1 in VSMC
      proliferation. Pim-1 was substantially induced in neointimal VSMCs of balloon
      injured rat carotid arteries, and in vivo infection with a dominant negative Pim
      1-expressing adenovirus (Ad-DN-Pim-1) markedly suppressed neointima formation and
      cell cycle progression in the balloon-injured arteries. In cultured VSMCs,
      treatment with serum or H(2)O(2) induced Pim-1 expression, and H(2)O(2)- or serum
      stimulated cell cycle progression and DNA synthesis were almost completely
      inhibited by DN-Pim-1 overexpression. Furthermore, we performed immunohisto
      chemical staining for Pim-1 in human thoracic aortas and coronary arteries
      obtained from six individuals at autopsy and found that Pim-1-positive cells are
      observed predominantly in the thickened intima of the aortas and coronary
      arteries. To the best of our knowledge, this is the first report showing Pim-1
      expression in rodent and human arterial walls. To summarize, Pim-1 expression was
      observed in the neointima of balloon-injured rat carotid arteries and in human
      thoracic aortas and coronary arteries showing intimal thickening, and the
      specific inhibition of Pim-1 function markedly suppressed neointima formation
      after balloon injury and the proliferation of cultured VSMCs, suggesting that Pim
      1 plays a role in VSMC proliferation.

PMID- 15471857
TI  - Overexpression of enzymatically active human cytosolic and mitochondrial
      thioredoxin reductase in HEK-293 cells. Effect on cell growth and
      differentiation.
AB  - The mammalian thioredoxin reductases (TrxR) are selenoproteins containing a
      catalytically active selenocysteine residue (Sec) and are important enzymes in
      cellular redox control. The cotranslational incorporation of Sec, necessary for
      activity, is governed by a stem-loop structure in the 3'-untranslated region of
      the mRNA and demands adequate selenium availability. The complicated translation
      machinery required for Sec incorporation is a major obstacle in isolating
      mammalian cell lines stably overexpressing selenoproteins. In this work we report
      on the development and characterization of stably transfected human embryonic
      kidney 293 cells that overexpress enzymatically active selenocysteine-containing
      cytosolic TrxR1 or mitochondrial TrxR2. We demonstrate that the overexpression of
      selenium-containing TrxR1 results in lower expression and activity of the
      endogenous selenoprotein glutathione peroxidase and that the activity of
      overexpressed TrxRs, rather than the protein amount, can be increased by selenium
      supplementation in the cell growth media. We also found that the TrxR
      overexpressing cells grew slower over a wide range of selenium concentrations,
      which was an effect apparently not related to increased apoptosis nor to fatally
      altered intracellular levels of reactive oxygen species. Most surprisingly, the
      TrxR1- or TrxR2-overexpressing cells also induced novel expression of the
      epithelial markers CK18, CK-Cam5.2, and BerEP4, suggestive of a stimulation of
      cellular differentiation.

PMID- 15471858
TI  - Purification, characterization, and sugar binding specificity of an N
      Glycolylneuraminic acid-specific lectin from the mushroom Chlorophyllum
      molybdites.
AB  - A carbohydrate-binding protein was isolated from the carpophores of the mushrooms
      and designated the Chlorophyllum molybdites lectin (CML) based on its origin. The
      molecular mass of CML was 32 kDa, and it was composed of two 16-kDa monomers with
      no disulfide bonds. Monosaccharide analysis indicated that 12% of the mass of CML
      was carbohydrate and consisted of GlcNAc:GalNAc:Gal:Man:l-Fuc in a molar ratio of
      1.5:1.9: 4.4:4.8:1.0. In the hemagglutination inhibition assay, CML exhibited the
      strongest binding specificity toward N-glycolylneuraminic acid (NeuGc) among the
      monosaccharides tested, whereas NeuAc did not inhibit the hemagglutination at
      all. GalNAc and Mealpha-GalNAc were also inhibitory at much higher concentrations
      than NeuGc. Among the glycoproteins, asialobovine submaxillary mucin (BSM) and
      porcine stomach mucin (PSM) showed strong inhibitory effects. In surface plasmon
      resonance analysis, asialo-BSM and PSM exhibited the strongest binding affinity.
      After co-injection of CML and NeuGc or GalNAc onto the asialo-BSM- or PSM
      immobilized chip, the dissociation of CML from the immobilized PSM was
      accelerated by NeuGc and GalNAc, but the dissociation of CML from the immobilized
      asialo-BSM was only promoted by GalNAc. These results and the other surface
      plasmon resonance experiments allowed us to conclude that the binding of asialo
      BSM to CML was because of an interaction between the lectin and the GalNAc
      residues of asialo-BSM, and both the NeuGc and GalNAc residues were responsible
      for the binding of PSM to CML. The results also suggested that CML had two
      different carbohydrate binding domains, one specific for NeuGc and the other for
      GalNAc.

PMID- 15471859
TI  - Bispecific minibodies targeting HER2/neu and CD16 exhibit improved tumor lysis
      when placed in a divalent tumor antigen binding format.
AB  - Unconjugated monoclonal antibodies have emerged as important therapeutic agents
      for selected malignancies. One mechanism by which antibodies can exert cytotoxic
      effects is antibody-dependent cellular cytotoxicity (ADCC). In an effort to
      increase the efficiency of ADCC at tumor sites, we have focused on the
      construction of bispecific antibodies specific for the tumor antigen HER2/neu and
      the Fc gamma RIII-activating receptor (CD16) found on NK cells, mononuclear
      phagocytes, and neutrophils. Here, we describe the production of bispecific
      minibodies in two distinct binding formats. The parent minibody was constructed
      such that the IgG1 C(H)3 constant domain serves as the oligomerization domain and
      is attached to an anti-CD16 and an anti-HER2/ neu single-chain Fv via 19- and 29
      amino acid linkers, respectively. This molecule can be expressed in mammalian
      cells from a dicistronic vector and has been purified using sequential affinity
      purification techniques. Analysis by surface plasmon resonance shows that the
      bispecific minibody can bind to HER2/neu and CD16, both individually and
      simultaneously. Furthermore, cytotoxicity studies show that the minibody can
      induce significant tumor cell lysis at a concentration as low as 20 nm. A
      trimeric, bispecific minibody (TriBi) that binds dimerically to HER2/neu and
      monomerically to CD16 induces equivalent cytotoxicity at lower antibody
      concentrations than either the parent minibody or the corresponding single-chain
      dimer. Both minibody constructs are stable in mouse and human serum for up to 72
      h at 37 degrees C. These minibodies have the potential to target solid tumors and
      promote tumor lysis by natural killer cells and mononuclear phagocytes.

PMID- 15471860
TI  - Stomatin modulates gating of acid-sensing ion channels.
AB  - Acid-sensing ion channels (ASICs) are H(+)-gated members of the
      degenerin/epithelial Na(+) channel (DEG/ENaC) family in vertebrate neurons.
      Several ASICs are expressed in sensory neurons, where they play a role in
      responses to nociceptive, taste, and mechanical stimuli; others are expressed in
      central neurons, where they participate in synaptic plasticity and some forms of
      learning. Stomatin is an integral membrane protein found in lipid/protein-rich
      microdomains, and it is believed to regulate the function of ion channels and
      transporters. In Caenorhabditis elegans, stomatin homologs interact with DEG/ENaC
      channels, which together are necessary for normal mechanosensation in the worm.
      Therefore, we asked whether stomatin interacts with and modulates the function of
      ASICs. We found that stomatin co-immunoprecipitated and co-localized with ASIC
      proteins in heterologous cells. Moreover, stomatin altered the function of ASIC
      channels. Stomatin potently reduced acid-evoked currents generated by ASIC3
      without changing steady state protein levels or the amount of ASIC3 expressed at
      the cell surface. In contrast, stomatin accelerated the desensitization rate of
      ASIC2 and heteromeric ASICs, whereas current amplitude was unaffected. These data
      suggest that stomatin binds to and alters the gating of ASICs. Our findings
      indicate that modulation of DEG/ENaC channels by stomatin-like proteins is
      evolutionarily conserved and may have important implications for mammalian
      nociception and mechanosensation.

PMID- 15471861
TI  - Transglutaminase 2 induces nuclear factor-kappaB activation via a novel pathway
      in BV-2 microglia.
AB  - Transglutaminase 2 (TGase 2) expression is increased in inflammatory diseases. We
      demonstrated previously that inhibitors of TGase 2 reduce nitric oxide (NO)
      generation in a lipopolysaccharide (LPS)-treated microglial cell line. However,
      the precise mechanism by which TGase 2 promotes inflammation remains unclear. We
      found that TGase 2 activates the transcriptional activator nuclear factor (NF)
      kappaB and thereby enhances LPS-induced expression of inducible nitric-oxide
      synthase. TGase 2 activates NF-kappaB via a novel pathway. Rather than
      stimulating phosphorylation and degradation of the inhibitory subunit alpha of NF
      kappaB (I-kappaBalpha), TGase2 induces its polymerization. This polymerization
      results in dissociation of NF-kappaB and its translocation to the nucleus, where
      it is capable of up-regulating a host of inflammatory genes, including inducible
      nitric-oxide synthase and tumor necrosis factor alpha (TNF-alpha). Indeed, TGase
      inhibitors prevent depletion of monomeric I-kappaBalpha in the cytosol of cells
      overexpressing TGase 2. In an LPS-induced rat brain injury model, TGase
      inhibitors significantly reduced TNF-alpha synthesis. The findings are consistent
      with a model in which LPS-induced NF-kappaB activation is the result of
      phosphorylation of I-kappaBalpha by I-kappaB kinase as well as I-kappaBalpha
      polymerization by TGase 2. Safe and stable TGase2 inhibitors may be effective
      agents in diseases associated with inflammation.

PMID- 15471862
TI  - Limited redundancy of the proprotein convertase furin in mouse liver.
AB  - Furin is an endoprotease of the family of mammalian proprotein convertases and is
      involved in the activation of a large variety of regulatory proteins by cleavage
      at basic motifs. A large number of substrates have been attributed to furin on
      the basis of in vitro and ex vivo data. However, no physiological substrates have
      been confirmed directly in a mammalian model system, and early embryonic
      lethality of a furin knock-out mouse model has precluded in vivo verification of
      most candidate substrates. Here, we report the generation and characterization of
      an interferon inducible Mx-Cre/loxP furin knock-out mouse model. Induction
      resulted in near-complete ablation of the floxed fur exon in liver. In sharp
      contrast with the general furin knock-out mouse model, no obvious adverse effects
      were observed in the transgenic mice after induction. Histological analysis of
      the liver did not reveal any overt deviations from normal morphology. Analysis of
      candidate substrates in liver revealed complete redundancy for the processing of
      the insulin receptor. Variable degrees of redundancy were observed for the
      processing of albumin, alpha(5) integrin, lipoprotein receptor-related protein,
      vitronectin and alpha(1)-microglobulin/bikunin. None of the tested substrates
      displayed a complete block of processing. The absence of a severe phenotype
      raises the possibility of using furin as a local therapeutic target in the
      treatment of pathologies like cancer and viral infections, although the observed
      redundancy may require combination therapy or the development of a more broad
      spectrum convertase inhibitor.

PMID- 15471863
TI  - CD200 receptor family members represent novel DAP12-associated activating
      receptors on basophils and mast cells.
AB  - Modulation by balancing activating and inhibitory receptors constitutes an
      important mechanism for regulating lymphocyte and myeloid cell effector
      responses. Using a microarray screen during parasitic helminth infection, we
      identified CD200 receptor-like 3 as a transcript highly expressed in basophils.
      Novel splice variants were present that generated proteins that differed in
      surface expression. The second immunoglobulin-like domain, encoded by exon 4, was
      required for cell surface expression and recruitment of DAP12 to the cell
      surface. Splice variants also generated unique cytoplasmic domains, which
      contributed to efficient pairing with DAP12. Despite expression on basophils and
      mast cells, which are integral components of allergic immunity, the absence of
      DAP12 did not alter effector cell recruitment or the host response elicited by
      helminth infection with Nippostrongylus brasiliensis.

PMID- 15471864
TI  - The viral protein A238L inhibits cyclooxygenase-2 expression through a nuclear
      factor of activated T cell-dependent transactivation pathway.
AB  - Cyclooxygenase-2 is transiently induced upon cell activation or viral infections,
      resulting in inflammation and modulation of the immune response. Here we report
      that A238L, an African swine fever virus protein, efficiently inhibits
      cyclooxygenase-2 gene expression in Jurkat T cells and in virus-infected Vero
      cells. Transfection of Jurkat cells stably expressing A238L with cyclooxygenase-2
      promoter-luciferase constructs containing 5'-terminal deletions or mutations in
      distal or proximal nuclear factor of activated T cell (NFAT) response elements
      revealed that these sequences are involved in the inhibition induced by A238L.
      Overexpression of a constitutively active version of the calcium-dependent
      phosphatase calcineurin or NFAT reversed the inhibition mediated by A238L on
      cyclooxygenase-2 promoter activation, whereas overexpression of p65 NFkappaB had
      no effect. A238L does not modify the nuclear localization of NFAT after phorbol
      12-myristate 13-acetate/calcium ionophore stimulation. Moreover, we show that the
      mechanism by which the viral protein down-regulates cyclooxygenase-2 activity
      does not involve inhibition of the binding between NFAT and its specific DNA
      sequences into the cyclooxygenase-2 promoter. Strikingly, A238L dramatically
      inhibited the transactivation mediated by a GAL4-NFAT fusion protein containing
      the N-terminal transactivation domain of NFAT1. Taken together, these data
      indicate that A238L down-regulates cyclooxygenase-2 transcription through the
      NFAT response elements, being NFAT-dependent transactivation implicated in this
      down-regulation.

PMID- 15471865
TI  - A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4)
      causes proximal tubular acidosis and glaucoma through ion transport defects.
AB  - In humans and terrestrial vertebrates, the kidney controls systemic pH in part by
      absorbing filtered bicarbonate in the proximal tubule via an electrogenic
      Na+/HCO3- cotransporter (NBCe1/SLC4A4). Recently, human genetics revealed that
      NBCe1 is the major renal contributor to this process. Homozygous point mutations
      in NBCe1 cause proximal renal tubular acidosis (pRTA), glaucoma, and cataracts
      (Igarashi, T., Inatomi, J., Sekine, T., Cha, S. H., Kanai, Y., Kunimi, M.,
      Tsukamoto, K., Satoh, H., Shimadzu, M., Tozawa, F., Mori, T., Shiobara, M., Seki,
      G., and Endou, H. (1999) Nat. Genet. 23, 264-266). We have identified and
      functionally characterized a novel, homozygous, missense mutation (S427L) in
      NBCe1, also resulting in pRTA and similar eye defects without mental retardation.
      To understand the pathophysiology of the syndrome, we expressed wild-type (WT)
      NBCe1 and S427L-NBCe1 in Xenopus oocytes. Function was evaluated by measuring
      intracellular pH (HCO3- transport) and membrane currents using microelectrodes.
      HCO3- -elicited currents for S427L were approximately 10% of WT NBCe1, and CO2
      induced acidification was approximately 4-fold faster. Na+ -dependent HCO3-
      transport (currents and acidification) was also approximately 10% of WT. Current
      voltage (I-V) analysis reveals that S427L has no reversal potential in HCO3-,
      indicating that under physiological ion gradient conditions, NaHCO3 could not
      move out of cells as is needed for renal HCO3- absorption and ocular pressure
      homeostasis. I-V analysis without Na+ further shows that the S427L-mediated
      NaHCO3 efflux mode is depressed or absent. These experiments reveal that voltage-
      and Na+ -dependent transport by S427L-hkNBCe1 is unfavorably altered, thereby
      causing both insufficient HCO3- absorption by the kidney (proximal RTA) and
      inappropriate anterior chamber fluid transport (glaucoma).

PMID- 15471866
TI  - N-retinylidene-phosphatidylethanolamine is the preferred retinoid substrate for
      the photoreceptor-specific ABC transporter ABCA4 (ABCR).
AB  - ABCA4, a member of the family of ATP binding cassette (ABC) proteins found in rod
      and cone photoreceptors, has been implicated in the transport of retinoid
      compounds across the outer segment disk membrane following the photoactivation of
      rhodopsin. Mutations in the ABCA4 gene are responsible for Stargardt macular
      dystrophy and related retinal degenerative diseases that cause a loss in vision.
      To identify the retinoid substrate that interacts with ABCA4, we have isolated
      ABCA4 from rod outer segment disk membranes on an immunoaffinity matrix and
      analyzed retinoid compounds that bind to ABCA4 using high performance liquid
      chromatography and radiolabeling methods. When all-trans-retinal was added to
      ABCA4 in the presence of phosphatidylethanolamine, approximately 0.9 mol of N
      retinylidene-phosphatidylethanolamine and 0.3 mol of all-trans-retinal were bound
      per mol of ABCA4 with an apparent K(d) of 2-5 microm. ATP and GTP released these
      retinoids from ABCA4, whereas ADP, GDP, and nonhydrolyzable derivatives,
      adenosine 5'-(beta,gamma-imido)triphosphate and guanosine 5'-(beta,gamma
      imido)triphosphate, were ineffective. One mole of N-retinyl
      phosphatidylethanolamine, the reduced form of N-retinylidene
      phosphatidylethanolamine, bound per mol of ABCA4, whereas 0.3 mol of all-trans
      retinal were bound in the absence of phosphatidylethanolamine. No binding of all
      trans-retinol to ABCA4 was observed. Our results indicate that ABCA4
      preferentially binds N-retinylidene-phosphatidylethanolamine with high affinity
      in the absence of ATP. Our studies further suggest that ATP binding and
      hydrolysis induces a protein conformational change that causes N-retinylidene
      phosphatidylethanolamine to dissociate from ABCA4.

PMID- 15471868
TI  - Dimerization of the human receptors for prostacyclin and thromboxane facilitates
      thromboxane receptor-mediated cAMP generation.
AB  - Prostacyclin (PGI(2)) and thromboxane (TxA(2)) are biological opposites; PGI(2),
      a vasodilator and inhibitor of platelet aggregation, limits the deleterious
      actions of TxA(2), a vasoconstrictor and platelet activator. The molecular
      mechanisms involved in the counterregulation of PGI(2)/TxA(2) signaling are
      unclear. We examined the interaction of the receptors for PGI(2) (IP) and TxA(2)
      (TPalpha). IP-induced cAMP and TP-induced inositol phosphate generation were
      unaltered when the receptors were co-expressed in HEK 293 cells (IP/TPalpha-HEK).
      TP-cAMP generation, in response to TP agonists or a TP-dependent isoprostane,
      iPE(2)III, was evident in IP/TPalpha-HEK and in aortic smooth muscle cells, but
      not in cells expressing either receptor alone, or in IP-deficient aortic smooth
      muscle cells. Augmentation of TP-induced cAMP generation, with the IP agonist
      cicaprost, was ablated in IP-deficient cells and was independent of direct IP
      signaling. IP/TPalpha heterodimers were formed constitutively when the receptors
      were co-expressed, with no overt changes in ligand binding to the individual
      receptor sites. However, despite inefficient binding of iPE(2)III to either the
      IP or TPalpha, expressed alone or in combination, robust cAMP generation was
      evident in IP/TPalpha-HEK, suggesting the formation of an alternative receptor
      site. Thus, IP/TPalpha dimerization was coincident with TP-cAMP generation,
      promoting a "PGI(2)-like" cellular response to TP activation. This represents a
      previously unknown mechanism by which IP may limit the cellular effects of TP.

PMID- 15471867
TI  - A loss of insulin-like growth factor-2 imprinting is modulated by CCCTC-binding
      factor down-regulation at senescence in human epithelial cells.
AB  - The imprinted insulin-like growth factor-2 (IGF2) gene is an auto/paracrine
      growth factor expressed only from the paternal allele in adult tissues. In
      tissues susceptible to aging-related cancers, including the prostate, a
      relaxation of IGF2 imprinting is found, suggesting a permissive role for
      epigenetic alterations in cancer development. To determine whether IGF2
      imprinting is altered in cellular aging and senescence, human prostate epithelial
      and urothelial cells were passaged serially in culture to senescence. Allelic
      analyses using an IGF2 polymorphism demonstrated a complete conversion of the
      IGF2 imprint status from monoallelic to biallelic, in which the development of
      senescence was associated with a 10-fold increase in IGF2 expression. As a
      mechanism, a 2-fold decrease in the binding of the enhancer-blocking element
      CCCTC-binding factor (CTCF) within the intergenic IGF2-H19 region was found to
      underlie this switch to biallelic IGF2 expression in senescent cells. This
      decrease in CTCF binding was associated with reduced CTCF expression in senescent
      cells. No de novo increases in methylation at the IGF2 CTCF binding site were
      seen. The forced down-regulation of CTCF expression using small interfering RNA
      in imprinted prostate cell lines resulted in an increase in IGF2 expression and a
      relaxation of imprinting. Our data suggest a novel mechanism for IGF2 imprinting
      regulation, that is, the reduction of CTCF expression in the control of IGF2
      imprinting. We also demonstrate that altered imprinting patterns contribute to
      changes in gene expression in aging cells.

PMID- 15471869
TI  - Signaling events involved in macrophage chemokine expression in response to
      monosodium urate crystals.
AB  - Chemokine production has been associated with leukocyte infiltration into the
      joint during gouty arthritis, and monosodium urate (MSU) crystals, the causative
      agent of this arthropathy, have been shown to modulate their expression. In the
      present study, we investigated the transductional mechanisms underlying this
      cellular regulation in the murine macrophage cell line B10R. We report that MSU
      crystals rapidly and transiently increase mRNA levels of various chemokines in a
      concentration-dependent manner. Examination of second messenger activation
      revealed that macrophage exposure to MSU crystals led to MEK1/2, ERK1/2, and
      inhibitory protein kappaBalpha phosphorylation as well as to NF-kappaB and AP-1
      nuclear translocation. Of interest, specific blockage of the ERK1/2 pathway
      drastically reduced up-modulation of MSU crystal-mediated chemokine production
      and activation of nuclear factors. Similarly, selective inhibition of NF-kappaB
      suppressed NF-kappaB DNA binding activity and the induction of all chemokine
      transcripts. These findings indicate that ERK1/2-dependent signals seem to be
      required for AP-1 and NF-kappaB activation and subsequent mRNA expression of the
      various macrophage chemokines. In addition, transcription and stability assays
      performed in presence of actinomycin D showed that MSU crystal-mediated MIP-1beta
      mRNA up-regulation resulted solely from transcriptional control, whereas that of
      MIP-1alpha, MIP-2, and MCP-1 was due to both gene transcription activation and
      mRNA posttranscriptional stabilization. Overall, the results of this study help
      to define the molecular events that govern macrophage chemokine regulation in
      response to MSU crystals, which is of paramount importance to better understand,
      and eventually to tame, the inflammatory response during acute gout.

PMID- 15471870
TI  - Characterization of the GRK2 binding site of Galphaq.
AB  - Heterotrimeric guanine nucleotide-binding proteins (G proteins) transmit signals
      from membrane bound G protein-coupled receptors (GPCRs) to intracellular effector
      proteins. The G(q) subfamily of Galpha subunits couples GPCR activation to the
      enzymatic activity of phospholipase C-beta (PLC-beta). Regulators of G protein
      signaling (RGS) proteins bind to activated Galpha subunits, including Galpha(q),
      and regulate Galpha signaling by acting as GTPase activating proteins (GAPs),
      increasing the rate of the intrinsic GTPase activity, or by acting as effector
      antagonists for Galpha subunits. GPCR kinases (GRKs) phosphorylate agonist-bound
      receptors in the first step of receptor desensitization. The amino termini of all
      GRKs contain an RGS homology (RH) domain, and binding of the GRK2 RH domain to
      Galpha(q) attenuates PLC-beta activity. The RH domain of GRK2 interacts with
      Galpha(q/11) through a novel Galpha binding surface termed the "C" site. Here,
      molecular modeling of the Galpha(q).GRK2 complex and site-directed mutagenesis of
      Galpha(q) were used to identify residues in Galpha(q) that interact with GRK2.
      The model identifies Pro(185) in Switch I of Galpha(q) as being at the crux of
      the interface, and mutation of this residue to lysine disrupts Galpha(q) binding
      to the GRK2-RH domain. Switch III also appears to play a role in GRK2 binding
      because the mutations Galpha(q)-V240A, Galpha(q)-D243A, both residues within
      Switch III, and Galpha(q)-Q152A, a residue that structurally supports Switch III,
      are defective in binding GRK2. Furthermore, GRK2-mediated inhibition of Galpha(q)
      Q152A-R183C-stimulated inositol phosphate release is reduced in comparison to
      Galpha(q)-R183C. Interestingly, the model also predicts that residues in the
      helical domain of Galpha(q) interact with GRK2. In fact, the mutants Galpha(q)
      K77A, Galpha(q)-L78D, Galpha(q)-Q81A, and Galpha(q)-R92A have reduced binding to
      the GRK2-RH domain. Finally, although the mutant Galpha(q)-T187K has greatly
      reduced binding to RGS2 and RGS4, it has little to no effect on binding to GRK2.
      Thus the RH domain A and C sites for Galpha(q) interaction rely on contacts with
      distinct regions and different Switch I residues in Galpha(q).

PMID- 15471871
TI  - Ligand-dependent activation of the farnesoid X-receptor directs arginine
      methylation of histone H3 by CARM1.
AB  - In this study we demonstrate that the class II nuclear hormone receptor,
      farnesoid X-receptor (FXR), incorporates histone methyltransferase activity
      within the gene locus for bile salt export pump (BSEP), a well established FXR
      target gene that functions as an ATP-dependent canalicular bile acid transporter.
      This methyltransferase activity is directed specifically to arginine 17 of
      histone H3. We demonstrate that FXR is directly associated with co-activator
      associated arginine methyltransferase 1 (CARM1) activity. Furthermore, we show by
      chromatin immunoprecipitation that the ligand-dependent activation of the human
      BSEP locus is associated with a simultaneous increase of FXR and CARM1
      occupation. The increased occupation of the BSEP locus by CARM1 also corresponds
      with the increased deposition of Arg-17 methylation and Lys-9 acetylation of
      histone H3 within the FXR DNA-binding element of BSEP. Consistent with these
      findings, CARM1 led to increased BSEP promoter activity with an intact FXR
      regulatory element, whereas CARM1 failed to transactivate the BSEP promoter with
      a mutated FXRE. Induction of endogenous BSEP mRNA and Arg-17 methylation by FXR
      regulatory element ligand, CDCA, requires CARM1 activity. Therefore, histone
      methylation at Arg-17 by CARM1 is a downstream target of signaling through ligand
      mediated activation of FXR. Our studies provide evidence that FXR directly
      recruits specific chromatin modifying activity of CARM1 necessary for full
      potentiation of the BSEP locus in vivo.

PMID- 15471872
TI  - Functional analysis of FAD-dependent thymidylate synthase ThyX from Paramecium
      bursaria Chlorella virus-1.
AB  - Sequence analysis of the 330-kb double-stranded DNA genome of Paramecium bursaria
      chlorella virus-1 revealed an open reading frame A674R that encodes a protein
      with up to 53% amino acid identity to a recently discovered new class of
      thymidylate synthases, called ThyX. Unlike the traditional thymidylate synthase,
      ThyA, that uses methylenetetrahydrofolate (CH(2)H(4)folate) as both a source of
      the methylene group and the reductant, CH(2)H(4)folate only supplies the
      methylene group in ThyX-catalyzed reactions. Furthermore, ThyX only catalyzes
      thymidylate (dTMP) formation in the presence of reduced pyridine nucleotides and
      oxidized FAD. The distribution and transcription patterns of the a674r gene in
      Chlorella viruses were examined. The a674r gene was cloned, and the protein was
      expressed in Escherichia coli. Biochemical characterization of the P. bursaria
      chlorella virus-1 recombinant ThyX protein indicates that it is more efficient at
      converting dUMP to dTMP than previously studied ThyX enzymes, thus allowing more
      detailed mechanistic studies of the enzyme. The ThyX-dUMP complexes with bound
      FAD function as efficient NAD(P)H oxidases, indicating that dUMP binds to the
      enzyme prior to NAD(P)H. This oxidation activity is directly linked to FAD
      reduction. Our results indicate that ThyX-specific inhibitors can be designed
      that do not affect ThyA enzymes. Finally, a model is proposed for the early
      stages of ThyX catalysis.

PMID- 15471873
TI  - Catalytic residues of the telomere resolvase ResT: a pattern similar to, but
      distinct from, tyrosine recombinases and type IB topoisomerases.
AB  - ResT is a member of the telomere resolvases, a newly discovered class of DNA
      breakage and reunion enzymes. These enzymes are involved in the formation of co
      valently closed hairpin DNA ends that are found in linear prokaryotic chromosomes
      and plasmids. The hairpins are generated by telomere resolution, where the
      replicated linear DNA ends are processed by DNA breakage followed by joining of
      DNA free ends to the complementary strand of the same molecule. Previous studies
      have shown that ResT catalyzes hairpin formation through a two-step
      transesterification similar to tyrosine recombinases and type IB topoisomerases.
      In the present study we have probed the reaction mechanism of ResT. The enzyme
      was found to efficiently utilize a substrate with a 5'-bridging phosphorothiolate
      at each cleavage site, similar to tyrosine recombinases/type IB topoisomerases.
      Using such a substrate to trap the covalent protein-DNA intermediate, coupled
      with affinity purification and mass spectroscopy, we report a new, non
      radioactive approach to directly determine the position of the amino acid in the
      protein, which is linked to the DNA. We report that tyrosine 335 is the active
      site nucleophile in ResT, strengthening the link between ResT and tyrosine
      recombinases/type IB topoisomerases. However, a distinct pattern of catalytic
      residues with similarities, but distinct differences from the above enzymes was
      suggested. The differences include the apparent absence of a general acid
      catalyst, as well as the dispensability of the final histidine in the RKHRHY
      hexad. Finally, two signature motifs (GRR(2X)E(6X)F and LGH(4-6X)T(3X)Y) near the
      catalytic residues of aligned telomere resolvases are noted.

PMID- 15471874
TI  - Inhibition of transcription factor activity by nuclear compartment-associated Bcl
      2.
AB  - Using a reporter gene assay in PC12, HEK293, HeLa, and NIH-3T3 cells, we show
      that the anti-apoptotic protein Bcl-2 significantly inhibits transcriptional
      activation of various transcription factors, including NF kappa B, AP1, CRE, and
      NFAT. A Bcl-2 mutant lacking its BH4 domain (Delta BH4) also inhibited
      transcription, whereas a Bcl-2 mutant lacking its transmembrane domain (Delta TM)
      was ineffective. Furthermore, Bcl-2 chimeric proteins containing transmembrane
      domains from the mitochondrial protein monoamine oxidase B (MaoB) or the
      endoplasmic reticulum protein cytochrome b(5) showed no effect on transcription
      factor activity. Subcellular localization studies showed that under conditions of
      transient transfection, the active Bcl-2 forms (wild type and Delta BH4) were
      predominantly found in the nuclear fraction, whereas the non-active forms (Delta
      TM, MaoB, and cytochrome b(5)) were in the non-nuclear fraction. Additionally,
      stably expressed Bcl-2 loses its ability to inhibit transcriptional activation
      and localizes predominantly to the non-nuclear fraction. Expression of FKBP38 (a
      chaperone that shuttles Bcl-2 to the mitochondria) removes co-expressed Bcl-2
      from the nuclear fraction and reverses its effect on transcription factor
      activity. Finally, using an inducible gene expression system, we show that
      nuclear compartment-associated Bcl-2 prevents entry of NF kappa B subunits to the
      nucleus without affecting NF kappa B release from its cytosolic inhibitory sub
      unit I kappa B alpha. These results suggest that (a) Bcl-2 suppresses
      transcriptional activity of multiple transcription factors; (b) Bcl-2 does not
      interfere with NF kappa B activation but prevents entrance of its active subunits
      to the nucleus; (c) membrane anchoring is required for this function of Bcl-2;
      and (d) association of Bcl-2 with the nuclear compartment is also necessary. We
      speculate that nuclear compartment-associated Bcl-2 may affect nuclear
      trafficking of multiple factors necessary for transcriptional activity.

PMID- 15471875
TI  - Cyr61 suppresses growth of human endometrial cancer cells.
AB  - Cyr61 (CCN1) is a member of the CCN protein family; these secreted proteins are
      involved in diverse biological processes such as cell adhesion, angiogenesis,
      apoptosis, and either growth arrest or growth stimulation depending on the
      cellular context. We studied the role of Cyr61 in endometrial tumorigenesis.
      Levels of Cyr61 were decreased in endometrial tumors compared with normal
      endometrium. Knockdown of Cyr61 expression by RNA interference in a well
      differentiated endometrial adenocarcinoma cell line (Ishikawa) stimulated its
      cellular growth. Conversely, overexpression of the protein in the
      undifferentiated AN3CA endometrial cancer cell line decreased their growth
      concurrently with increased apoptosis in liquid culture. These same cells had
      decreased clonogenic capacity and a nearly complete loss of tumorigenicity in
      vivo. Furthermore, partially purified Cyr61 suppressed growth of endometrial
      cancer cells. The increased apoptosis in these endometrial cancer cells with
      forced overexpression of Cyr61 was associated with elevated expression of the pro
      apoptotic proteins Bax, Bad, and TRAIL (tumor necrosis factor receptor-associated
      ligand). Cyr61-induced caspase-3 activation and depolarization of mitochondrial
      membrane. In summary, endometrial cancer cells have decreased expression of Cyr61
      compared with normal endometrium, and this lowered expression may provide the
      transformed cells a growth advantage over their normal counterpart.

PMID- 15471876
TI  - Two novel mutant human adenylosuccinate lyases (ASLs) associated with autism and
      characterization of the equivalent mutant Bacillus subtilis ASL.
AB  - An Australian patient with autism was found to be heterozygous for two mutations
      in the gene encoding adenylosuccinate lyase (ASL), resulting in the protein
      mutations E80D and D87E. The patient's mother carried only the E80D mutation. The
      equivalent positions are 62 and 69 in Bacillus subtilis ASL. Although both human
      and B. subtilis enzymes normally have Asp at position 87 (or 69), the B. subtilis
      ASL has Ile and Asp at 62 and 65, respectively, whereas human ASL has Glu and Arg
      at the equivalent positions. We have constructed, expressed, and purified the
      double mutant I62E/D65R as a "humanized" normal B. subtilis enzyme to compare
      with enzymes with a single mutation at position 62 (I62D/D65R), at position 69
      (I62E/D65R/D69E), or at both positions (I62D/D65R/D69E). V(max) for conversion of
      adenylosuccinate to AMP and fumarate is 0.57 micromol/min/mg for I62E/D65R, 0.064
      micromol/min/mg for I62D/D65R, 0.27 micromol/min/mg for I62E/D65R/D69E, and 0.069
      micromol/min/mg for I62D/D65R/D69E. The K(m) for adenylosuccinate is elevated in
      the X62D mutants, and I62D/D65R is the least stable of these ASLs at 37 degrees
      C. The CD spectra of mutant and wild type enzymes are similar; thus, there are no
      appreciable structural changes. Clearly the Asp(62) causes the most drastic
      effect on ASL function, whereas the Glu(69) mutation produces only modest change.
      These results emphasize the importance of expanding tests for ASL deficiency to
      individuals with developmental delay of any severity, including individuals with
      autistic spectrum disorder. This study further demonstrates the usefulness of the
      B. subtilis ASL as a model to mimic the defective enzyme in ASL deficiency.

PMID- 15471877
TI  - Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      induces phosphorylation of mu- and m-calpain in association with increased
      secretion, cell migration, and invasion.
AB  - Mounting evidence indicates that cigarette smoking not only promotes
      tumorigenesis but also may increase the spread of cancer cells in the body.
      However, the intracellular mechanism(s) by which cigarette smoking promotes
      metastasis of human lung cancer remains enigmatic. Nitrosamine 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an important component in
      cigarette smoke and is formed by nitrosation of nicotine. mu- and m-calpain
      (calpain I and calpain II) are major members of the calpain family, which are
      ubiquitously expressed in both small cell lung cancer and non-small cell lung
      cancer cells. Our findings indicated that NNK potently induces phosphorylation of
      both mu- and m-calpain in association with their activation and increased
      migration as well as invasion of lung cancer cells. Treatment of cells with
      PD98059 blocked phosphorylation of m- and mu-calpain and resulted in suppression
      of NNK-induced cell migration and invasion. p44 MAPK/extracellular signal
      regulated kinase 1 (ERK1) and p42 MAPK/ERK2 were activated by NNK, co-localized
      with mu- and m-calpain in cytoplasm, and directly phosphorylated mu- and m
      calpain in vitro. These findings suggest a role for the ERK1/2 kinases as NNK
      activated physiological calpain kinases. Specific knock-down of mu- and/or m
      calpain expression by RNA interference blocked NNK-stimulated migration and
      invasion, suggesting that mu- and m-calpain may act as required targets in a NNK
      induced metastatic signaling pathway. Furthermore, NNK promotes secretion of
      active mu- and m-calpain from lung cancer cells through vesicles, which may have
      the potential to cleave substrates in the extracellular matrix. Thus, NNK-induced
      cell migration and invasion may occur, at least in part, through a novel
      mechanism involving phosphorylation of calpains that leads to their activation
      and secretion, which may contribute to metastasis and/or progression of lung
      cancer.

PMID- 15471878
TI  - The nuclear tyrosine kinase BRK/Sik phosphorylates and inhibits the RNA-binding
      activities of the Sam68-like mammalian proteins SLM-1 and SLM-2.
AB  - Expression of the intracellular tyrosine kinase BRK/Sik is epithelial-specific
      and regulated during differentiation. Only a few substrates have been identified
      for BRK/Sik, including the KH domain containing RNA-binding protein Sam68 and the
      novel adaptor protein BKS. Although the physiological role of Sam68 is unknown,
      it has been shown to regulate mRNA transport, pre-mRNA splicing, and
      polyadenylation. Here we demonstrate that the Sam68-like mammalian proteins SLM-1
      and SLM-2 but not the related KH domain containing heterogeneous nuclear
      ribonucleoprotein K are novel substrates of BRK/Sik. The expression of active
      BRK/Sik results in increased SLM-1 and SLM-2 phosphorylation and increased
      retention of BRK/Sik within the nucleus. The phosphorylation of SLM-1 and SLM-2
      has functional relevance and leads to inhibition of their RNA-binding abilities.
      We show that SLM-1, SLM-2, and BRK/Sik have restricted patterns of expression
      unlike the ubiquitously expressed Sam68. Moreover, BRK/Sik, SLM-1, and Sam68
      transcripts were coexpressed in the mouse gastrointestinal tract and skin,
      suggesting that SLM-1 and Sam68 could be physiologically relevant BRK/Sik targets
      in vivo. The ability of BRK/Sik to negatively regulate the RNA-binding activities
      of the KH domain RNA binding proteins SLM-1 and Sam68 may have an impact on the
      posttranscriptional regulation of epithelial cell gene expression.

PMID- 15471879
TI  - Surface-exposed hemophilic mutations across the factor VIII C2 domain have
      variable effects on stability and binding activities.
AB  - Factor VIII (fVIII) is a plasma glycoprotein that functions as an essential
      cofactor in blood coagulation. Its carboxyl-terminal "C2" domain is responsible
      for binding to both activated platelet surfaces and von Willebrand factor. We
      characterized the effect of 20 hemophilia-associated missense mutations across
      this domain (that all occur in patients in vivo) on its stability and its binding
      activities. At least six of these mutations were severely destabilizing, and
      another four caused moderate destabilization and corresponding reductions in both
      binding functions. One mutant (A2201P) displayed a significant reduction in its
      membrane binding activity but normal von Willebrand factor binding, while two
      others (P2300S and R2304H) caused the opposite effect. Several mutations
      (including L2210P, V2223M, M2238V, and R2304C) displayed near wild-type
      stabilities and binding activities and may instead affect mRNA splicing or
      alternative properties or functions of the protein. This study demonstrated that
      von Willebrand factor and membrane binding activities can be uncoupled and
      uniquely disrupted by different mutations and that either effect can lead to
      similar reductions in clotting activity. It also illustrated how a heterogeneous
      genetic disorder causes diverse molecular phenotypes that result in similar
      disease states.

PMID- 15471880
TI  - Cyclin-dependent kinase 5 phosphorylates serine 31 of tyrosine hydroxylase and
      regulates its stability.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine
      biosynthesis, and its activity is regulated by phosphorylation in the N-terminal
      regulatory domain. The proline-directed serine/threonine kinase cyclin-dependent
      kinase 5 (cdk5) plays an important role in diverse neuronal processes. In the
      present study, we identify TH as a novel substrate of cdk5. We show that cdk5
      phosphorylates TH at serine 31 and that this phosphorylation is associated with
      an increase in total TH activity. In transgenic mice with increased cdk5
      activity, the immunoreactivity for phosphorylated TH at Ser-31 is enhanced in
      neurons of the substantia nigra, a brain region enriched with TH-positive
      neurons. In addition, we demonstrate that co-expression of cdk5 and its
      regulatory activator p35 with TH increases the stability of TH. Consistent with
      these findings, TH protein levels are reduced in cdk5 knock-out mice.
      Importantly, the TH activity and protein turnover of the phosphorylation
      defective mutant TH S31A was not altered by cdk5 activity. Taken together, these
      data suggest that cdk5 phosphorylation of TH is an important regulator of TH
      activity through stabilization of TH protein levels.

PMID- 15471881
TI  - Delayed and sustained activation of extracellular signal-regulated kinase in
      human keratinocytes by UVA: implications in carcinogenesis.
AB  - Exposure to the sun's UV radiation appears to be the most important environmental
      factor involved in the development of skin cancer. UVA is the major portion of UV
      radiation in sunlight and is considered to be a human carcinogen. In this study,
      we have investigated the delayed and sustained activation of ERK MAPK by UVA
      exposure. In parallel, a delayed Ras activation with a similar time course was
      observed after UVA exposure. The activated Ras was found to be localized in
      endomembranes such as the Golgi apparatus instead of plasma membranes. Expression
      of dominant negative Ras (N17Ras) abolished ERK activation by UVA. The presence
      of AG1478, an epidermal growth factor (EGF) receptor (EGFR) kinase inhibitor, had
      no effect on ERK or Ras activation, indicating that EGFR kinase activity is not
      involved in ERK activation by UVA. In contrast, protein kinase C (PKC) depletion
      by chronic 12-O-tetradecanoylphorbol-13-acetate treatment nearly abolished UVA
      induced ERK and Ras activation. The presence of the Ca(2+)-dependent-PKC
      inhibitor Go6976 had a similar effect. These findings suggest that ERK activation
      by UVA is mediated by PKC in a Ras-dependent pathway. In addition, a gradual
      increase in intracellular calcium level after UVA exposure was detected by flow
      cytometry. The presence of the PLC inhibitor U73122 or the calcium chelator 1,2
      bis(2-aminophenoxy)ethane-N,N, N',N'-tetraacetic acid tetrakis (acetoxymethyl
      ester) (BAPTA-AM) blocked both ERK and Ras activation, suggesting that both PLC
      and calcium are required for ERK activation. Our findings demonstrated that,
      different from UVC and UVB, UVA-induced delayed and sustained ERK activation is
      EGFR kinase activity-independent, but PLC/calcium/PKC-mediated. The delayed and
      sustained ERK activation provides a survival signal to human HaCaT keratinocytes,
      which may serve as an important mechanism for cell transformation and potential
      skin carcinogenesis in vivo caused by UVA exposure.

PMID- 15471882
TI  - Chromatin domain boundaries delimited by a histone-binding protein in yeast.
AB  - When located next to chromosomal elements such as telomeres, genes can be
      subjected to epigenetic silencing. In yeast, this is mediated by the propagation
      of the SIR proteins from telomeres toward more centromeric regions. Particular
      transcription factors can protect downstream genes from silencing when tethered
      between the gene and the telomere, and they may thus act as chromatin domain
      boundaries. Here we have studied one such transcription factor, CTF-1, that binds
      directly histone H3. A deletion mutagenesis localized the barrier activity to the
      CTF-1 histone-binding domain. A saturating point mutagenesis of this domain
      identified several amino acid substitutions that similarly inhibited the boundary
      and histone binding activities. Chromatin immunoprecipitation experiments
      indicated that the barrier protein efficiently prevents the spreading of SIR
      proteins, and that it separates domains of hypoacetylated and hyperacetylated
      histones. Together, these results suggest a mechanism by which proteins such as
      CTF-1 may interact directly with histone H3 to prevent the propagation of a
      silent chromatin structure, thereby defining boundaries of permissive and silent
      chromatin domains.

PMID- 15471883
TI  - Vaccinia virus intermediate stage transcription is complemented by Ras-GTPase
      activating protein SH3 domain-binding protein (G3BP) and cytoplasmic
      activation/proliferation-associated protein (p137) individually or as a
      heterodimer.
AB  - Transcription of the DNA genome of vaccinia virus occurs in the cytoplasm and is
      temporally programmed by early, intermediate, and late stage-specific
      transcription factors in conjunction with a viral multisubunit RNA polymerase.
      The RNA polymerase, capping enzyme, and three factors (VITF-1, VITF-2, and VITF
      3) are sufficient for in vitro transcription of a DNA template containing an
      intermediate stage promoter. Vaccinia virus intermediate transcription factor
      (VITF)-1 and -3 are virus-encoded, whereas VITF-2 was partially purified from
      extracts of uninfected HeLa cells. Using purified and recombinant viral proteins,
      we showed that the HeLa cell factor was required for transcription of linear or
      nicked circular templates but not of super coiled DNA. HeLa cell polypeptides of
      approximately 110 and 66 kDa copurified with VITF-2 activity through multiple
      chromatographic steps. The polypeptides were separated by SDS-polyacrylamide gel
      electrophoresis and identified by mass spectrometry as Ras-GTPase-activating
      protein SH3 domain-binding protein (G3BP) and p137, recently named cytoplasmic
      activation/proliferation-associated protein-1. The co-purification of the two
      polypeptides with transcription-complementing activity was confirmed with
      specific antibodies, and their association with each other was demonstrated by
      affinity chromatography of tagged recombinant forms. Furthermore, recombinant
      G3BP and p137 expressed individually or together in mammalian or bacterial cells
      complemented the activity of the viral RNA polymerase and transcription factors.
      The involvement of cellular proteins in transcription of intermediate stage genes
      may regulate the transition between early and late phases of vaccinia virus
      replication.

PMID- 15471884
TI  - DNA binding domain in the replication checkpoint protein Mrc1 of
      Schizosaccharomyces pombe.
AB  - The replication checkpoint is activated when replication forks are obstructed by
      DNA lesions or protein complexes bound to DNA or when DNA synthesis is restrained
      by the limited availability of deoxyribonucleotides. This checkpoint preserves
      genome integrity by stabilizing stalled forks and delaying the onset of mitosis.
      In the fission yeast Schizosaccharomyces pombe, Mrc1 is a replication checkpoint
      adaptor protein that allows the sensor kinase Rad3-Rad26 to activate the effector
      kinase Cds1. In Saccharomyces cerevisiae, Mrc1 associates with replication forks
      and co-precipitates with the DNA replication protein Cdc45. Whether or not Mrc1
      interacts directly with DNA is unknown. Here we define a approximately 150 amino
      acid DNA binding domain (DBD) in the N-terminal region of S. pombe Mrc1. The DBD
      interacts preferentially with branched DNA structures in vitro. Deletion of the
      DBD or point mutations that diminish its DNA binding activity render cells
      sensitive to the replication inhibitor hydroxyurea. These mutations also impair
      the replication checkpoint arrest. The DBD has a helix-loop-helix motif that is
      predicted to bind DNA. This motif is conserved in the recently identified N
      terminal DBD of human Claspin, a presumptive homolog of yeast Mrc1 proteins.

PMID- 15471885
TI  - Phosphorylation of p53 on key serines is dispensable for transcriptional
      activation and apoptosis.
AB  - The p53 tumor suppressor is a key mediator of the cellular response to stress.
      Phosphorylation induced by multiple stress-activated kinases has been proposed to
      be essential for p53 stabilization, interaction with transcriptional co
      activators, and activation of p53 target genes. However, genetic studies suggest
      that stress-activated phosphorylation may not be essential for p53 activation. We
      therefore investigated the role of p53 phosphorylation on six key serine residues
      (Ser(6), Ser(15), Ser(20), Ser(37), Ser(46), and Ser(392)) for p53 activation
      using nutlin-3, a recently developed small molecule MDM2 antagonist. We show here
      that nutlin does not induce the phosphorylation of p53. Comparison of the
      activity of unphosphorylated and phosphorylated p53 induced by the genotoxic
      drugs doxorubicin and etoposide in HCT116 and RKO cells revealed no difference in
      their sequence-specific DNA binding and ability to transactivate p53 target genes
      and to induce p53-dependent apoptosis. We conclude that p53 phosphorylation on
      six major serine sites is not required for activation of p53 target genes or
      biological responses in vivo.

PMID- 15471886
TI  - Platinated DNA adducts enhance poisoning of DNA topoisomerase I by camptothecin.
AB  - Camptothecins constitute a novel class of chemotherapeutics that selectively
      target DNA topoisomerase I (Top1) by reversibly stabilizing a covalent enzyme-DNA
      intermediate. This cytotoxic mechanism contrasts with that of platinum drugs,
      such as cisplatin, which induce inter- and intrastrand DNA adducts. In vitro
      combination studies using platinum drugs combined with Top1 poisons, such as
      topotecan, showed a schedule-dependent synergistic activity, with promising
      results in the clinic. However, whereas the molecular mechanism of these single
      agents may be relatively well understood, the mode of action of these
      chemotherapeutic agents in combination necessitates a more complete
      understanding. Indeed, we recently reported that a functional homologous
      recombination pathway is required for cisplatin and topotecan synergy yet
      represses the synergistic toxicity of 1-beta-D-arabinofuranosyl cytidine in
      combination with topotecan (van Waardenburg, R. C., de Jong, L. A., van Delft,
      F., van Eijndhoven, M. A., Bohlander, M., Bjornsti, M. A., Brouwer, J., and
      Schellens, J. H. (2004) Mol. Cancer Ther. 3, 393-402). Here we provide direct
      evidence for Pt-1,3-d(GTG) poisoning of Top1 in vitro and demonstrate that
      persistent Pt-DNA adducts correlate with increased covalent Top1-DNA complexes in
      vivo. This contrasts with a lack of persistent lesions induced by the alkylating
      agent bis[chloroethyl]nitrosourea, which exhibits only additive activity with
      topotecan in a range of cell lines. In human IGROV-1 ovarian cancer cells, the
      synergistic activity of cisplatin with topotecan requires processive DNA
      polymerization, whereas overexpression of Top1 enhances yeast cell sensitivity to
      cisplatin. These results indicate that the cytotoxic activity of cisplatin is
      due, in part, to poisoning of Top1, which is exacerbated in the presence of
      topotecan.

PMID- 15471887
TI  - Interconnections of CLN3, Hook1 and Rab proteins link Batten disease to defects
      in the endocytic pathway.
AB  - The endosomal/lysosomal transmembrane protein CLN3 is mutated in the Batten
      disease (juvenile neuronal ceroid lipofuscinosis, JNCL). However, the molecular
      mechanism of JNCL pathogenesis and the exact function of the CLN3 protein have
      remained unclear. Previous studies have shown that deletion of BTN1, the yeast
      orthologue of CLN3, leads to increased expression of BTN2. BTN2 encodes Btn2p, a
      proposed homologue to a novel microtubule-binding protein Hook1, which regulates
      endocytosis in Drosophila. We analysed here the putative interconnection between
      CLN3 and Hook1 in the mammalian cells and discovered that overexpression of human
      CLN3 induces aggregation of Hook1 protein, potentially by mediating its
      dissociation from the microtubules. Using in vitro binding assay we were able to
      demonstrate a weak interaction between Hook1 and the cytoplasmic segments of
      CLN3. We also found receptor-mediated endocytosis to be defective in CLN3
      deficient JNCL fibroblasts, connecting CLN3, Hook1 and endocytosis in the
      mammalian system. Moreover, co-immunoprecipitation experiments showed that Hook1
      physically interacts with endocytic Rab7, Rab9 and Rab11, hence delineating a
      manifold role for mammalian Hook1 in membrane trafficking events. These novel
      interactions between the microtubule-binding Hook1 and the large family of Rab
      GTPases also suggest a link between CLN3 function, microtubule cytoskeleton and
      endocytic membrane trafficking.

PMID- 15471888
TI  - A mouse model of AChR deficiency syndrome with a phenotype reflecting the human
      condition.
AB  - The two subtypes of mammalian muscle nicotinic acetylcholine receptors (AChR) are
      generated by the substitution of the epsilon (adult) subunit for the gamma
      (fetal) subunit within the AChR pentamer. Null mutations of the adult AChR
      epsilon-subunit gene are the most common cause of the AChR deficiency syndrome.
      This is a disorder of neuromuscular transmission characterized by non-progressive
      fatigable muscle weakness present throughout life. In contrast with the human
      disorder, mice with AChR epsilon-subunit null mutations die between 10 and 14
      weeks of age. We generated transgenic mice that constitutively express the human
      AChR gamma-subunit in an AChR epsilon-subunit 'knock-out' background. These mice,
      in which neuromuscular transmission is mediated by fetal AChR, live well into
      adult life but show striking similarities to human AChR deficiency syndrome. They
      display fatigable muscle weakness, reduced miniature endplate potentials and
      endplate potentials, reduced motor endplate AChR number and altered endplate
      morphology. Our results illustrate how species differences in the control of ion
      channel gene expression may affect disease phenotype, demonstrate that expression
      of adult AChR subtype is not essential for long-term survival, and suggest that
      in patients with AChR deficiency syndrome, up-regulation of the gamma-subunit
      could be a beneficial therapeutic strategy.

PMID- 15471889
TI  - The co-inheritance of type 1 diabetes and multiple sclerosis in Sardinia cannot
      be explained by genotype variation in the HLA region alone.
AB  - Type 1 diabetes (T1D) and multiple sclerosis (MS) are two autoimmune diseases
      which exhibit a considerably higher incidence in Sardinia compared with the
      surrounding southern European populations. Surprisingly, a 5-fold increased
      prevalence of T1D has also been observed in Sardinian MS patients. Susceptibility
      to both disorders is associated with common variants of the HLA-DRB1 and -DQB1
      loci. In this study, we determined the relative contribution of genotype
      variation of these loci to the co-occurrence of the two disorders in Sardinia. We
      genotyped 1052 T1D patients and 1049 MS patients (31 of whom also had T1D)
      together with 1917 ethnically matched controls. On the basis of the absolute
      risks for T1D of the HLA-DRB1-DQB1 genotypes, we established that these loci
      would only contribute to a 2-fold increase in T1D prevalence in MS patients. From
      this evidence, we conclude that shared disease associations due to the HLA-DRB1
      DQB1 loci provide only a partial explanation for the observed increased
      prevalence of T1D in Sardinian MS patients. The data suggest that variation at
      other non-HLA class II loci, and/or unknown environmental factors contribute
      significantly to the co-occurrence of these two traits.

PMID- 15471890
TI  - The product of X-linked Kallmann's syndrome gene (KAL1) affects the migratory
      activity of gonadotropin-releasing hormone (GnRH)-producing neurons.
AB  - X-linked Kallmann's syndrome (KS) is a genetic disease characterized by anosmia
      and hypogonadism due to impairment in the development of olfactory axons and in
      the migration of gonadotropin-releasing hormone (GnRH)-producing neurons.
      Deletions or point mutations of a gene located at Xp22.3 (KAL1) are responsible
      for the disease. This gene encodes for a secreted heparin-binding protein (KAL or
      anosmin-1) which exhibits similarities with cell-adhesion molecules. In the
      present study, we show for the first time a direct action of anosmin-1 on the
      migratory activity of GnRH neurons. Specifically, we exposed immortalized
      migrating GnRH neurons (GN11 cells) to conditioned media (CM) of COS or CHO cells
      transiently transfected with human KAL1 gene in microchemotaxis and collagen gel
      assays. We found that anosmin-1-enriched media produced a cell-specific
      chemotactic response of GN11 cells. None of the CM enriched on three forms of
      anosmin-1 carrying different missense mutations (N267K, E514K and F517L) found in
      patients affected by X-linked KS affected the chemomigration of GN11 cells.
      Anosmin binds to the GN11 cell surface by interacting with the heparan sulphate
      proteoglycans, and the chemotactic effect of anosmin-1-enriched CM can be
      specifically blocked by heparin or by heparitinase pretreatment. These results
      strongly suggest an involvement of anosmin-1 in the control of the migratory
      behaviour of GnRH neurons and provide novel information on the pathogenesis of
      KS.

PMID- 15471893
TI  - Hemoglobin adducts in workers exposed to nitrotoluenes.
AB  - Nitrotoluenes are important intermediates in the chemical industry. 2,6
      Dinitrotoluene (26DNT), 2,4-dinitrotoluene (24DNT) and 2-nitrotoluene are
      carcinogenic in animals and possibly carcinogenic in humans. It is therefore
      important to develop methods to biomonitor workers exposed to such chemicals.
      Hemoglobin (Hb) adducts of nitroarenes are established markers of the biological
      effective dose. We developed a method to measure Hb adducts in biological
      samples. Hb adducts were measured in rats after a single exposure (0.5 mmol/kg)
      of 24DNT, 26DNT, 2,4-toluenediamine (24TDA) and 26TDA. Hydrolysis of Hb from rats
      dosed with 24DNT yields, 4-amino-2-nitrotoluene (4A2NT) (16.3 nmol/g Hb), 24TDA
      (4.3 nmol/g Hb) and 4-acetylamino-2-aminotoluene (4AA2AT) (0.51 nmol/g Hb).
      Hydrolysis of Hb from rats dosed with 26DNT yields three amines, 2-amino-6
      nitrotoluene (2A6NT) (2.5 nmol/g Hb), 26TDA (1.2 nmol/g Hb) and 2-acetylamino-6
      aminotoluene (2AA6AT) (0.17 nmol/g Hb). A similar Hb adduct pattern was found in
      Chinese workers exposed to nitrotoluenes. With respect to 24DNT, 4A2NT was the
      predominant adduct, and the amount was approximately 24-fold higher than 24TDA.
      With respect to 26DNT, 2A6NT was the predominant adduct, and the amount was
      approximately 20-fold higher than 26TDA. With respect to the mononitrotoluenes,
      the Hb adduct of 2NT was present in the highest concentrations. Each worker was
      examined for adverse health effects linked to exposure to DNT. The health effects
      were compared with the Hb adduct levels using logistic regression analysis. The
      odds of suffering from inertia were 3.2 times higher [95% confidence interval
      (CI) = 1.8-5.8] when the level of 4A2NT Hb adducts increased by one log-unit.
      Similar odds ratios were observed with somnolence (3.1, CI = 1.4-6.9), nausea
      (2.4, CI = 1.3-4.3) and dizziness (5.5, CI = 1.3-24.2). These results inferred
      that quantification of DNT-Hb adducts provided an effective biomarker of toxicity
      and could be used to estimate the risk associated with a particular exposure to
      DNT.

PMID- 15471892
TI  - Raised granzyme B levels are associated with erosions in patients with early
      rheumatoid factor positive rheumatoid arthritis.
AB  - BACKGROUND: Raised granzyme B in serum and synovium of patients with rheumatoid
      arthritis suggests a role for cytotoxic T cells and natural killer cells in the
      pathogenesis of this disease. OBJECTIVE: To evaluate serum granzyme B in patients
      with early arthritis and correlate it with specific diagnosis and clinical
      indices of disease severity. METHODS: 257 patients with inflammatory arthritis
      for less than one year (46% rheumatoid arthritis, 17% spondyloarthropathy, 37%
      undifferentiated arthritis) had a prospective clinical, serological, and
      radiographic evaluation. Granzyme B was measured in initial sera by ELISA.
      Patients were HLA typed for DR alleles using sequence specific primers. A
      logistic regression model was used to evaluate the potential prognostic value of
      serum granzyme B in predicting radiographic erosions after one year of follow up.
      RESULTS: Granzyme B values were similar in rheumatoid arthritis,
      spondyloarthropathy, and undifferentiated arthritis. Concentrations were higher
      in rheumatoid factor (RF) positive patients than in RF negative patients (mean
      (SD): 3.15 (0.92) v 2.89 (0.71) pg/ml; p<0.05). After one year, erosions were
      present in 30% of patients in the overall cohort, and in 44% of patients with
      rheumatoid arthritis. In the entire cohort, serum granzyme B did not predict
      erosions independently. However, high granzyme B was an independent predictor of
      early erosions in patients with RF positive rheumatoid arthritis (odds ratio =
      4.83 (95% confidence interval, 1.13 to 20.59)) (p<0.05). CONCLUSIONS: Granzyme B
      may be a useful prognostic marker in early rheumatoid arthritis and may provide
      important clues to the pathogenesis of this disease.

PMID- 15471891
TI  - EULAR evidence based recommendations for the management of hip osteoarthritis:
      report of a task force of the EULAR Standing Committee for International Clinical
      Studies Including Therapeutics (ESCISIT).
AB  - OBJECTIVE: To develop evidence based recommendations for the management of hip
      osteoarthritis (OA). METHODS: The multidisciplinary guideline development group
      comprised 18 rheumatologists, 4 orthopaedic surgeons, and 1 epidemiologist,
      representing 14 European countries. Each participant contributed up to 10
      propositions describing key clinical aspects of hip OA management. Ten final
      recommendations were agreed using a Delphi consensus approach. Medline, Embase,
      CINAHL, Cochrane Library, and HTA reports were searched systematically to obtain
      research evidence for each proposition. Where possible, outcome data for
      efficacy, adverse effects, and cost effectiveness were abstracted. Effect size,
      rate ratio, number needed to treat, and incremental cost effectiveness ratio were
      calculated. The quality of evidence was categorised according to the evidence
      hierarchy. The strength of recommendation was assessed using the traditional A-D
      grading scale and a visual analogue scale. RESULTS: Ten key treatment
      propositions were generated through three Delphi rounds. They included 21
      interventions, such as paracetamol, NSAIDs, symptomatic slow acting disease
      modifying drugs, opioids, intra-articular steroids, non-pharmacological
      treatment, total hip replacement, osteotomy, and two general propositions. 461
      studies were identified from the literature search for the proposed interventions
      of efficacy, side effects, and cost effectiveness. Research evidence supported 15
      interventions in the treatment of hip OA. Evidence specific for the hip was
      strikingly lacking. Strength of recommendation varied according to category of
      research evidence and expert opinion. CONCLUSION: Ten key recommendations for the
      treatment of hip OA were developed based on research evidence and expert
      consensus. The effectiveness and cost effectiveness of these recommendations were
      evaluated and the strength of recommendation was scored.

PMID- 15471894
TI  - Reduced nucleotide excision repair and GSTM1-null genotypes influence anti
      B[a]PDE-DNA adduct levels in mononuclear white blood cells of highly PAH-exposed
      coke oven workers.
AB  - It is important to identify the potential genetic-susceptible factors that are
      able to modulate individual responses to exposure to carcinogenic polycyclic
      aromatic hydrocarbons (PAHs). In the present study we evaluated the influence of
      four polymorphisms of nucleotide excision repair (NER) genes [xeroderma
      pigmentosum-C (XPC)-PAT +/-, xeroderma pigmentosum-A (XPA) 5' non-coding region
      A23G, XPD-exon 23 A35931C Lys751Gln, xeroderma pigmentosum-D (XPD)-exon 10
      G23591A Asp312Asn] and that of glutathione S-transferase mu1 (GSTM1-active or 
      null) on benzo[a]pyrene diol epoxide (B[a]PDE)-DNA adduct levels from the lympho
      monocyte fraction (LMF) of highly PAH benzo[a]pyrene (B[a]P)-exposed Polish coke
      oven workers (n = 67, 67% current smokers) with individual urinary post-shift
      excretion of 1-pyrenol exceeding the proposed biological exposure index (BEI)
      (2.28 micromol/mol creatinine). The bulky (+/-)-r-7,t-8-dihydroxy-t-9,10-oxy
      7,8,9,10-tetrahydrobenzo[a]pyrene (anti-B[a]PDE)-DNA adduct levels were detected
      by high-performance liquid chromatography (HPLC)/fluorescence analysis and
      genotypes by polymerase chain reaction. We found that workers with the low DNA
      repair capacity of XPC-PAT+/+ and XPA-A23A genotypes had significantly increased
      anti-B[a]PDE-DNA adduct levels (Mann-Whitney U-test, z = 2.24, P = 0.02 and z =
      2.65, P = 0.01). Moreover, DNA adducts were also raised in workers without GSTM1
      activity (GSTM1-null genotype) (Mann-Whitney U-test, z = 2.25, P = 0.0246).
      Workers with unfavourable XPC-PAT+/+ and XPA-A23A NER genotypes, alone
      (approximately 65% of workers) or combined with GSTM1-null genotype
      (approximately 75% of workers) were in the tertile with the highest adduct level,
      i.e. >4.11 adducts/10(8) nt (chi2 = 5.85, P = 0.0156 and chi2 = 5.40, P = 0.01).
      The increase in anti-B[a]PDE-DNA adduct levels (ln values) was significantly
      related in a multiple linear regression analysis to PAH exposure (i.e. urinary
      post-shift excretion of 1-pyrenol) (t = 2.61, P = 0.0115), lack of GSTM1 activity
      (t = 2.41, P = 0.0192) and to low DNA repair capacity of the XPC-PAT+/+ genotype
      (t = 2.34, P = 0.0226). The influence of the XPA-A23A genotype was not evident in
      this statistical analysis, and no associations with XPD polymorphisms, dietary
      habits or tobacco smoking were found. The modulation of anti-B[a]PDE-DNA adducts
      in the LMF by GSTM1-null and some low-activity NER genotypes may be considered as
      a potential genetic susceptibility factor capable of modulating individual
      responses to PAH (B[a]P) genotoxic exposure and the consequent risk of cancer in
      coke oven workers.

PMID- 15471895
TI  - Targeted over-expression of mPGES-1 and elevated PGE2 production is not
      sufficient for lung tumorigenesis in mice.
AB  - There is a significant body of evidence suggesting that enzymes involved in
      arachidonic acid metabolism and their eicosanoid products play a role in various
      cancers, having both pro- and antitumorigenic effects. The goal of this study was
      to further define the role microsomal prostaglandin E synthases (mPGES-1) play in
      lung tumorigenesis. Transgenic mice were created with targeted over-expression of
      human mPGES-1 in the alveolar and airway epithelial cells using an SP-C promoter
      driven construct. Transgene positive (mPGES-1+) mice were shown to significantly
      over-express functional mPGES-1 in the lung and more specifically in alveolar
      type II cells. To study the effects of mPGES-1 over-expression in lung tumor
      formation, mice were exposed to a complete carcinogen protocol with a single
      injection of urethane or an initiation/promotion model with a single injection of
      3-methylcholanthrene (MCA) followed by multiple injections of butylated
      hydroxytoluene (BHT). mPGES-1+ mice did not show a significant difference in
      tumor multiplicity or tumor size at 10, 16, 19 or 30 weeks after urethane
      injection compared with mPGES-1- mice. No significant difference was seen in
      tumor incidence, multiplicity or size at 19 weeks after treatment with MCA/BHT.
      Western blots verified that mPGES-1 expression was increased in tumors versus
      uninvolved tissue of both mPGES-1+ and mPGES-1- mice with overall expression
      being significantly higher in mPGES-1+ mice. Cyclooxygenase-2 levels were
      elevated in tumors in both groups. From these studies we conclude that over
      expression of mPGES-1 and highly elevated PGE2 production are not sufficient to
      induce lung tumors.

PMID- 15471896
TI  - Up-regulation of interleukin-6 in human ovarian cancer cell via a Gi/PI3K-Akt/NF
      kappaB pathway by lysophosphatidic acid, an ovarian cancer-activating factor.
AB  - Bioactive lysophospholipid, lysophosphatidic acid (LPA), is consistently raised
      in the ascites of patients with ovarian cancer. Interleukin-6 (IL-6) is a
      pleiotropic cytokine, which is assumed to be involved in ovarian carcinogenesis.
      However, the regulation of IL-6 in ovarian cancer remains largely unknown. To
      elucidate the pathogenesis of ovarian cancer, this study investigated how LPA
      affects IL-6 production in ovarian cancer cells. Experimental results indicated
      that LPA stimulates IL-6 expression in all ovarian cancer cell lines tested, but
      not in normal ovarian surface epithelial (NOSE) cells, owing to the lack of LPA
      specific Edg4 and/or Edg7 receptors in NOSE cells. This work demonstrated that
      LPA transcriptionally activates IL-6 expression, which can be totally blocked by
      the pertussis toxin, indicating that Gi-mediated signaling is critically involved
      in inducing IL-6 by LPA. Pharmacological and genetic inhibition assays revealed
      that Gi-mediated PI3K activation phosphorylated downstream Akt and subsequently
      induced NF-kappaB activation causes the induction of IL-6 by LPA in SK-OV-3
      cells. In summary, data presented here demonstrate that LPA is an important
      inducer of IL-6 and LPA-regulated IL-6 expression via a Gi/PI3K-Akt/NF-kappaB
      pathway in ovarian cancer cells, providing molecular therapeutic targets for
      treating ovarian cancer.

PMID- 15471897
TI  - Pas1 haplotype-dependent genetic predisposition to lung tumorigenesis in rodents:
      a meta-analysis.
AB  - Rodent species and strains show wide variations in susceptibility to lung
      tumorigenesis. In mice, hierarchical clustering of 29 inbred laboratory strains
      by pulmonary adenoma susceptibility 1 (Pas1) locus polymorphisms separated the
      strains into either an A/J- or a C57BL/6J-type Pas1 haplotype. A pooled analysis
      (including >8500 mice) of studies on spontaneous and chemically induced lung
      tumorigenesis in these strains revealed a significantly higher risk of
      spontaneous lung tumors [odds ratio (OR) 12.17; 95% confidence interval (CI) 9.00
      16.45] as well as of chemically induced lung tumors (OR 15.14; 95% CI 12.51
      18.31) in the A/J-type haplotype. Strain differences were observed with six
      different carcinogens, suggesting that Pas1 locus activity is carcinogen
      independent. Thus, the present meta-analysis indicates a link between the genetic
      control of spontaneous and chemically induced lung tumor susceptibility in mice.
      The Pas1 susceptibility allele is frequent in the population of inbred mouse
      strains, whereas a counterpart appears to be absent or rare in rat and hamster
      strains. These findings might help in the interpretation of results of rodent
      carcinogenicity bioassays and assessing the risk of lung carcinogenesis from
      chemicals.

PMID- 15471898
TI  - A beta-catenin-dependent pathway regulates expression of cytochrome P450 isoforms
      in mouse liver tumors.
AB  - Phenobarbital (PB) is a model tumor promoter in the rodent liver. In the mouse,
      the promotional effect of PB results from a selective stimulation of clonal
      outgrowth of hepatocytes harboring activating mutations in the beta-catenin
      (catnb) gene. Glutamine synthetase (GS), a downstream target in the Wnt/beta
      catenin/T-cell factor (TCF) signaling pathway, is strongly up-regulated in catnb
      mutated mouse liver tumors and may serve as a marker for their identification.
      Here we show that the levels of several cytochrome P450 (CYP) isoenzymes are also
      altered in GS-positive liver tumors. Immunohistochemical and western blotting
      analyses demonstrated that GS-positive, catnb-mutated tumors showed levels of
      CYP1A, CYP2B, CYP2C and CYP2E1, which were similar or slightly enhanced in
      comparison with non-tumoral liver tissue. This contrasts with tumors without
      catnb mutations, which exhibited decreased levels of these CYP isoforms. Real
      time RT-PCR revealed that the differences in CYP levels in the tumors
      corresponded to changes in the respective mRNAs. Mouse hepatoma cells were
      transiently transfected with an expression vector encoding an S33Y-mutated beta
      catenin protein, which was functional with regard to transactivation of a beta
      catenin/TCF-responsive (topflash) reporter construct. Co-transfected with
      luciferase reporter vectors containing either the regulatory upstream sequence of
      the CYP2B1 gene or three dioxin-responsive core elements were activated by S33Y
      beta-catenin. These results indicate that mutation of catnb leads to
      transcriptional activation of CYP isoenzymes in mouse liver tumors. As CYPs are
      involved in both the activation and the inactivation of several clinically
      important anticancer drugs, our findings may be relevant for chemotherapy of
      human cancers, where activation of beta-catenin-dependent signaling by mutation
      of the gene or alternative mechanisms is frequently observed.

PMID- 15471899
TI  - Induction of macroautophagy in human colon cancer cells by soybean B-group
      triterpenoid saponins.
AB  - The impact of triterpenoid saponins isolated from soybeans on suppression of
      colon cancer cell proliferation was evaluated. Experiments were conducted to
      determine the effects of a purified soybean B-group saponin extract on cell
      proliferation, cell-cycle distribution and programmed cell death in cultures of
      human HCT-15 colon adenocarcinoma cells. Treatment of cells with the soyasaponins
      at concentrations of 25-500 p.p.m. significantly reduced viable cell numbers
      after 24 and 48 h of exposure. Treatment of cells with 25 and 100 p.p.m. of
      saponins also resulted in a transient accumulation of cells in the S-phase of the
      cell cycle that was associated with a significant reduction of cyclin-dependant
      kinase-2 (CDK-2) activity. More striking was that, when examined by transmission
      electron microscopy, soyasaponin-treated cells exhibited an approximately 4.5
      fold increase in cell morphologies characteristic of Type II non-apoptotic
      programmed cell death (PCD) including numerous autophagic vacuoles, changes that
      collectively suggest autophagic cell death. In addition, the protein levels of
      microtubule-associated protein light chain 3 (LC-3), a specific marker of
      macroautophagy, increased substantially following soyasaponin treatment. Taken
      together these results thus indicate that soybean saponins, at physiologically
      relevant doses, can suppress HCT-15 colon cancer cell proliferation through S
      phase cell-cycle delay, and can induce macroautophagy, the hallmark of Type II
      PCD. These findings suggest that B-group soyasaponins may be another colon-cancer
      suppressive component of soy that warrants further examination as a potential
      chemopreventive phytochemical.

PMID- 15471900
TI  - Senescence and immortalization: role of telomeres and telomerase.
AB  - Telomere dynamics are a critical component of both aging and cancer. Telomeres
      progressively shorten in almost all dividing cells and most human cells do not
      express or maintain sufficient telomerase activity to fully maintain telomeres.
      There is accumulating evidence that when only a few telomeres are short, they
      form end-associations, leading to a DNA damage signal resulting in replicative
      senescence (a cellular growth arrest, also called the M1 stage). In the absence
      of cell-cycle checkpoint pathways (e.g. p53 and or p16/Rb), cells bypass M1
      senescence and telomeres continue to shorten eventually resulting in crisis (also
      called the M2 stage). M2 is characterized by many 'uncapped' chromosome ends, end
      fusions, chromosome breakage fusion-bridge cycles, mitotic catastrophe and a high
      fraction of apoptotic cells. In a rare M2 cell, telomerase (a cellular reverse
      transcriptase) can be reactivated or up-regulated, resulting in indefinite cell
      proliferation. This cellular immortalization is a potentially rate-limiting step
      in carcinogenesis that is important for the continuing evolution of most advanced
      cancers. In this perspective we will present our views on the evidence for
      telomere dysfunction in aging and in cancer progression. We will argue that
      telomere shortening in the absence of other alterations may be a potent tumor
      suppressor mechanism and we will discuss the evidence for and against the major
      molecular mechanisms proposed to initiate replicative senescence.

PMID- 15471901
TI  - Arsenite induces prominent mitotic arrest via inhibition of G2 checkpoint
      activation in CGL-2 cells.
AB  - Arsenic compounds, which are well-documented human carcinogens, are now used in
      cancer therapy. Knowledge of the mechanism by which arsenic exerts its toxicity
      may help in designing a more effective regimen for therapy. In this study, we
      showed that arsenite could induce prominent mitotic arrest in CGL-2 cells and
      demonstrated the presence of damaged DNA in arsenite-arrested mitotic cells. We
      then explored why these cells with arsenite-induced DNA damage were arrested at
      mitosis instead of G2 stage. When synchronized CGL-2 cells were treated with
      arsenite at stage G1, S or G2, all progressed into, and arrested at, the mitotic
      stage and contained damaged DNA, as demonstrated by the appearance of the DNA
      double-strand break marker, phosphorylated histone H2A.X (gamma-H2AX). Since X
      irradiation induced G2 arrest in CGL-2 cells, these cells clearly have a
      functional G2 DNA damage checkpoint. However, treatment of X-irradiated CGL-2
      cells with arsenite resulted in a decrease in G2 cells and an increase in mitotic
      cells, suggesting that arsenite may inhibit activation of the G2 DNA damage
      checkpoint and thus allow cells with damaged DNA to proceed from G2 into mitosis.
      Immunoblot analysis confirmed that arsenite treatment reduced the X-irradiation
      induced phosphorylation of both ataxia-telangiectasia, mutated at serine 1981 and
      Cdc25C at serine 216, events which are crucial for G2 checkpoint activation and
      G2 arrest. Moreover, a higher frequency of apoptotic cells is observed in mitotic
      CGL-2 cells arrested by arsenite than those arrested by nocodazole or taxol. Our
      results show that the combined effects of arsenite in inducing DNA damages,
      inhibiting the activation of G2 checkpoint, and arresting cells with damaged DNA
      in the mitotic stage may subsequently enhance the induction of apoptosis in
      arsenite-arrested mitotic CGL-2 cells.

PMID- 15471902
TI  - Hand coordination following capsular stroke.
AB  - Motor outcome following stroke of the internal capsule is variable and its
      determinants are poorly understood. While many patients fully regain their
      abilities, recovery of motor functions remains incomplete in others. We analysed
      functional motor tasks of the upper limb to determine the pattern of focal
      disability after a small infarct of the internal capsule ('pure motor stroke') in
      the chronic stage (mean 2.4 years after stroke) with kinematic recordings of a
      reaching-to-grasp movement, with a quantitative analysis of the precision grip,
      and with clinical rating scales. The location of the lesions within the posterior
      limb of the internal capsule (PLIC) in 18 patients was determined from
      neuroimages obtained in the acute stage (5-20 days after the insult). Involvement
      of the PLIC was assessed at the level of the basal ganglia, approximately 8 mm
      above the anterior commissure-posterior commissure level. The distance between
      the posterior edge of the internal capsule and the centre of gravity of the
      lesion was determined. Chronic disabilities affected dextrous movements, while
      paresis was mild and sensitivity for light touch or passive finger flexion was
      almost normal. For both the reaching-to-grasp movement and the precision grip
      paradigm, the slowness of movement or force development was confined to the
      phases when grip formation and stabilization occur, while the onset of hand
      transport and of the vertical lifting force were not delayed. Grip forces were
      increased. We observed a close correlation between posterior location within the
      PLIC and the altered measures of timing and precision grip force. The more
      posterior the acute lesion was located within the PLIC, the more pronounced were
      the chronic motor deficits, as seen both in the quantitative measures and in the
      rating scales. The present study demonstrates for the first time that the amount
      and quality of chronic motor deficits of dextrous movements are related to a
      simple measure drawn from routine neuroimaging in the acute stage in patients
      with capsular stroke. The poor motor outcome in lesions involving the most
      posterior parts of the PLIC could be due to the condensed organization of
      corticofugal projections and the density of pyramidal fibres from the primary
      motor cortex in this subsector. Even small infarcts of this strategic area can
      disrupt many of the projections from the motor cortices and could thereby limit
      recovery strategies between homolateral motor representations.

PMID- 15471903
TI  - Hyperexcitability of the primary somatosensory cortex in migraine--a
      magnetoencephalographic study.
AB  - The excitability of the cerebral cortex in the interictal state of migraine
      appears to be fundamental in the brain's susceptibility to migraine attacks.
      Subpopulations of cortical neurons are reported to have different physiological
      response properties to different interstimulus intervals (ISIs) and, hence, may
      be differentially altered or modulated in migraine. The aim of this study
      therefore was to evaluate response characteristics of temporally and spatially
      defined neuronal subpopulations in the cortex of migraineurs. To this end, we
      measured, by means of magnetoencephalography (37-channel neuromagnetometer), the
      response properties of the early components of the somatosensory evoked magnetic
      fields following electrical stimulation of the median nerve, the N20m and P35m,
      at ISIs ranging between 0.3 and 6 s. As a measure of the number of excited
      neurons underlying the N20m and P35m, we evaluated the root mean square (r.m.s.)
      of the deflections across all 37 channels at the corresponding latencies and the
      corresponding dipole moment of the equivalent current dipole (ECD strength).
      Twenty consecutive women with at least three migraine attacks/month (range 3
      8/month) fulfilling the International Headache Society criteria and 20 age
      matched healthy women were included in the study. In migraineurs, the r.m.s. and
      ECD strength of N20m was increased at all ISIs (r.m.s., P < 0.05; ECD strength, P
      < 0.01) and positively related to the mean attack frequency (r.m.s., R(s) = 0.6,
      P < 0.01; ECD strength, R(s) = 0.5, P < 0.05). In contrast, the r.m.s. and ECD
      strength of P35m did not differ significantly between migraineurs and control
      subjects and did not correlate significantly with the frequency of migraine
      attacks. Responses to different ISIs did not differ significantly between
      migraineurs and control subjects. The r.m.s. of N20m was stable for ISIs between
      0.5 and 6 s and decreased significantly at an ISI of 0.3 s. In contrast, the
      r.m.s. of P35m decreased continuously as the ISI was decreased below 6 s and this
      reached significance for an ISI of < or =1 s. Habituation of N20m or P35m, i.e. a
      decrease in response magnitude following repetitive stimulation over time, was
      not found in either the control subjects or in the migraineurs. It is concluded
      that the population of neurons in the primary somatosensory cortex underlying the
      N20m are hyperexcitable and that this hyperexcitability is linked to the
      frequency of migraine attacks. This hyperexcitability appears not to be related
      to habituation since habituation was not found in the control subjects. In
      contrast, the magnitude of P35m is not pathophysiologically linked to the
      interictal state of migraine. Furthermore, the cellular mechanisms causing ISI
      dependent depression of N20m and P35m are not altered in migraine.

PMID- 15471904
TI  - Systems and integrative pharmacology: putting the puzzle pieces together.

PMID- 15471905
TI  - Nora Volkow: motivated neuroscientist.
AB  - Nora Volkow claims to have always been curious about the workings of the human
      brain. Even as a medical student in her native Mexico, she investigated animal
      behavior with the ultimate goal of understanding human motivation. Upon
      completing her medical studies, in the early 80s, she moved to the U.S. to take
      advantage of emerging neuroimaging technologies, first during her psychiatry
      residency at New York University and Brookhaven National Laboratory, and then as
      a faculty member at the University of Texas in Houston. In Houston, Volkow
      embarked on seminal studies into human drug use and the functioning brain, which
      she continued to pursue, again at Brookhaven, during the subsequent two decades.
      Volkow established herself as an eminent researcher and proponent of
      neuroscience, and her insights into the brain have greatly advanced our
      appreciation of human behavior and motivation. In 2003, she took up her present
      position as Director of the National Institute on Drug Abuse.

PMID- 15471906
TI  - The role of reactive oxygen species (ROS) in persistent pain.

PMID- 15471907
TI  - An alternative to conventional immunosuppression: small-molecule inhibitors of
      Kv1.3 channels.

PMID- 15471908
TI  - Combating atherosclerosis with LXR alpha and PPAR alpha agonists: is rational
      multitargeted polypharmacy the future of therapeutics in complex diseases?

PMID- 15471909
TI  - Molecular effects of lithium.
AB  - Bipolar affective disorder is a common, severe, chronic, and often life
      threatening illness, associated with other medical and psychiatric conditions
      (i.e., co-morbidity). The treatment of this devastating disorder was
      revolutionized by the discovery of lithium's antimanic effects over fifty years
      ago. Recent molecular and cellular biological studies have identified a number of
      unexpected targets for this monovalent cation, notably glycogen synthase kinase-3
      and neurotrophic signaling cascades. These findings are leading to a
      reconceptualization of the biological underpinnings of bipolar disorder and are
      resulting in considerable interest in utilizing lithium for the treatment of
      certain neurodegenerative disorders. We review recent insights into lithium's
      actions including its direct inhibitory actions on inositol monophosphatase,
      inositol polyphosphate 1-phosphatase, glycogen synthase kinase-3, fructose 1,6
      bisphosphatase, bisphosphate nucleotidase, and phosphoglucomutase enzymes. We
      also discuss lithium's intracellular downstream targets including adenylate
      cyclase, the phosphoinositol cascade (and its effect on protein kinase C),
      arachidonic acid metabolism, and effects on neurotrophic cascades. Many of the
      new insights of lithium's actions may lead to the strategic development of
      improved therapeutics for the treatment of bipolar disorder.

PMID- 15471910
TI  - Mechanisms of radiation injury to the central nervous system: implications for
      neuroprotection.
AB  - The central nervous system (CNS) is a major dose-limiting organ in clinical
      radiotherapy (XRT). The underlying mechanisms of radiation-induced injury in this
      organ remain unclear. For many years, research has focused on identifying the
      major target cells of damage, and depletion of target cells due to reproductive
      or clonogenic cell death was believed to be the primary cause of tissue damage
      and organ failure. There is now an increasing body of data indicating that the
      response of the CNS after XRT is a continuous and interacting process. This
      review addresses some of the recent advances in our understanding of the
      mechanisms of CNS radiation damage. Specifically, the focus is on apoptotic cell
      death, and cell death and injury mediated by secondary damage. These potentially
      reversible components of the injury response provide important targets for
      neuroprotective interventions.

PMID- 15471911
TI  - Neuronal nicotinic receptor subtypes: defining therapeutic targets.
AB  - Humans have appreciated the beneficial properties of the tobacco plant for
      thousands of years. These effects include alertness, reduced anxiety, muscle
      relaxation, and analgesia. Yet it has been less than two decades since the
      central actions of nicotine have been examined in earnest for potential
      therapeutic applications. In fact, the cholinergic systems, in comparison to
      other neurotransmitter systems of the body, have been relatively poorly exploited
      in terms of therapeutic agents, and the muscarinic cholinergic systems have been
      relegated mainly to the treatment of gastrointestinal disorders and glaucoma; for
      the nicotinic system, antagonists are used to induce muscle paralysis during
      certain surgical procedures. For both families of cholinergic receptors,
      widespread exploitation in terms of therapeutics has been limited by significant
      side effect profiles associated with available cholinergic drugs.

PMID- 15471924
TI  - Characteristics of populations of granulosa cells from individual follicles in
      women undergoing 'coasting' during controlled ovarian stimulation (COS) for IVF.
AB  - BACKGROUND: The aim of this study was to evaluate the functional characteristics
      of granulosa cell populations of individual follicles of women undergoing
      controlled ovarian stimulation (COS) for IVF/ICSI in whom gonadotrophin had been
      withheld ('coasted') for the prevention of OHSS. METHODS: Follicular fluid and
      granulosa cells were isolated from 224 individual follicles in 41 women who had
      been coasted and from 257 individual follicles in 50 women who had a 'normal'
      response to COS. Cells were cultured at 10,000 cells per well, to evaluate
      progesterone secretion. Follicular fluid was assayed for progesterone and
      estradiol (E2). RESULTS: No significant differences were observed between the two
      groups with respect to granulosa cell number or follicular fluid progesterone and
      E2 and follicle size, the retrieval of an oocyte and the subsequent fertilization
      of the oocyte. However, the granulosa cells derived from the coasted group showed
      a higher rate of progesterone secretion per cell at 72 h which was sustained for
      longer. Differences were also seen at 72 and 120 h of culture with a loss of
      correlation between progesterone secretion and follicle diameter in the coasted
      group. CONCLUSIONS: Our findings suggest that coasting has an effect on the
      functional capacity of the granulosa cells and the duration of their function. It
      is likely that in women at risk of OHSS who are not coasted, the granulosa cells
      have the capacity to produce significantly more chemical mediators per cell and
      for a more prolonged period of time.

PMID- 15471925
TI  - Cytoplasmic droplets: the good, the bad or just confusing?
AB  - The term cytoplasmic droplets is used to mean two different structures by basic
      scientists and clinicians. The literature on the presence, position and loss of
      cytoplasmic droplets and their relationship to infertility in animal species is
      reviewed. It is proposed that a change in terminology is required: 'cytoplasmic
      droplet' should be used to describe normal droplets associated with functional
      sperm produced by normal spermatogenesis and 'excess residual cytoplasm' is
      suggested to describe abnormal droplets associated with dysfunctional sperm that
      are products of faulty spermatogenesis.

PMID- 15471926
TI  - Repeated clomiphene citrate challenge testing in the prediction of outcome in
      IVF: a comparison with basal markers for ovarian reserve.
AB  - BACKGROUND: The aim of this study was to investigate the predictive accuracy and
      clinical value of performing either a single or a repeated clomiphene citrate
      challenge test (CCCT) in predicting poor response in IVF, compared to that of
      currently used basal ovarian reserve markers. METHODS: Sixty-three patients
      undergoing their first IVF treatment were prospectively included. After
      measurement of basal markers on cycle day 3 (cd3) [FSH, inhibin B and antral
      follicle count (AFC)], a CCCT was performed. FSH and inhibin B levels were
      measured on day 10 (cd10). A second CCCT was performed after a washout period of
      one cycle. In all patients the tests were followed by an IVF treatment. Poor
      response (<4 oocytes or cancellation due to impaired (<3 follicles) or absent
      follicular growth) was used as primary outcome measure. RESULTS: Both the single
      as well as the repeated CCCT markers had a rather good discriminative potential
      for the prediction of poor response (area under the receiver operating
      characteristic curve (ROCAUC): FSH cd10=0.79, inhibin B cd10=0.79, mean FSH
      cd10=0.82 and mean inhibin B cd10=0.88). This compared well with the performance
      of the basal markers (FSH 0.82, inhibin B 0.72 and AFC 0.83). In a multivariate
      analysis on only the basal variables, FSH cd3 and AFC were selected (ROCAUC
      0.89). Only stepwise forward analysis on the repeated CCCT variables revealed a
      better discriminating potential for the prediction of poor response (ROCAUC
      0.92). At a specificity level of approximately 0.97, sensitivity and the positive
      predictive value were marginally improved in the CCCT models. CONCLUSIONS:
      Performing a CCCT (single or repeated) has a rather good ability to predict poor
      response in IVF. However, it appears that the predictive accuracy and clinical
      value of the CCCT is not clearly better than that of basal FSH in combination
      with an AFC. Therefore, the use of the CCCT as a predictor of outcome in IVF
      should not be advocated.

PMID- 15471927
TI  - The onset of the initial rise in follicle-stimulating hormone during the human
      menstrual cycle.
AB  - BACKGROUND: The rise in FSH (FSHr) that leads to the recruitment of a cohort of
      follicles during the menstrual cycle occurs during the luteal-follicular
      transition, however, it is unclear whether it consistently occurs on one
      particular day, or is subjected to reproductive ageing. METHODS: We determined
      the FSHr in 836 complete menstrual cycles from 102 women with regular menses
      using an algorithm, and additionally compared the relative variation in FSH
      during the last 14 days of the cycle. Possible effects of reproductive ageing on
      the onset of FSHr were also investigated. RESULTS: The day of FSHr follows a
      normal distribution with a median value of -4 (relative to first day of menses),
      mean -4.1 and SD 2.1. Analysis of the relative changes in FSH during the last 14
      days of the cycle revealed the first significant rise on day -4 (P=0.0033),
      coinciding with the first significant drop in estrogens (P=0.0002). No effect of
      chronological age, or initial FSH levels, on FSHr was found, however, there was
      an inverse relationship between total follicular phase length (from day of FSHr
      to LH peak) and initial FSH levels (P<0.0001). CONCLUSIONS: The initial FSH rise
      in the cycle occurs consistently 4 days before menses, is related to a drop in
      estrogen levels, and is not affected by reproductive ageing.

PMID- 15471928
TI  - Diagnostic assessment of the developmental potential of human cryopreserved
      ovarian tissue from multiple patients using xenografting.
AB  - BACKGROUND: Although ovarian tissue cryopreservation for women at risk of losing
      ovarian function is offered by many clinics, there is a lack of evidence relating
      to the developmental potential of the stored tissue and, therefore, its clinical
      potential. This study was designed to use xenografting of cryopreserved tissue
      from multiple patients to assess the reproducibility of preservating
      developmental potential, the variation in developing follicle profile and the
      relationship between pre-freeze histology and post-thaw development. METHODS:
      Using previously published methods, cryopreserved ovarian cortex from nine
      patients was thawed and grafted under the kidney capsules of immunodeficient
      mice. Development of follicles was assessed after 26 weeks and compared to
      histology prior to freezing. RESULTS: Multiple growing follicles including antral
      stages were observed in multiple grafts of tissue from all patients. Metaphase II
      oocytes (n=9) were observed in follicles in grafts from five patients. There was
      no relationship between pre-freeze histology and developing follicle profile in
      xenografts. CONCLUSIONS: The propanediol freezing method used in this study is
      capable of reproducibly preserving the developmental potential of human ovarian
      follicles. The developing follicle profile after cryopreservation cannot be
      accurately predicted from pre-freeze histology. Xenografting provides a powerful
      tool for assessing the potential of human cryopreserved ovarian tissue.

PMID- 15471929
TI  - Knowledge and attitudes towards preimplantation genetic diagnosis in Germany.
AB  - BACKGROUND: Preimplantation genetic diagnosis (PGD) is a technique which is often
      related to emotional debates because of its ethical and social implications.
      Worldwide there are different forms of legislation; Germany constitutes an
      interesting case because of the historical background concerning eugenics and
      dealing with handicapped persons at the time of national socialism. PGD is
      currently not legal but there are still polarized positions and legalization
      remains an issue. Studies about the attitudes of the general population towards
      PGD are rare. METHODS: Data were collected in a representative survey carried out
      in November 2003. Subjects were 2110 persons in Germany aged 18-50 years. RESULTS
      AND CONCLUSIONS: Respondents had little knowledge about PGD. There were incorrect
      assumptions about the diagnostic possibilities and a lack of basic genetic
      knowledge. A tendency towards a general acceptance of PGD for medical indications
      was found. Non-medical indications such as sex selection were generally not
      accepted. It could be observed that respondents who already had a notion about
      PGD overestimated the diagnostic possibilities and would eventually use PGD in
      the future more than respondents who had never heard about PGD before.

PMID- 15471930
TI  - The morphological normalcy of the sperm nucleus and pregnancy rate of
      intracytoplasmic injection with morphologically selected sperm.
AB  - BACKGROUND: Our preceding studies have already demonstrated the advantage of
      intracytoplasmic morphologically selected sperm injection (IMSI) over the
      conventional IVF-ICSI procedure in terms of pregnancy rate. This study was
      undertaken to determine whether the increased pregnancy outcome was attributable
      to the preferred nuclear morphology of the selected spermatozoa, and not to the
      special sperm preparation technique modified by IMSI. METHODS: Comparison between
      two matched IMSI groups, i.e. negative comprising 38 cycles, where no spermatozoa
      with intact nuclei were available for microinjection; and positive, involving
      ovum microinjection by spermatozoa with strictly defined morphologically normal
      nuclei. RESULTS: Implantation and pregnancy rates were significantly higher, and
      abortion rates significantly lower, in the positive group compared with the
      negative group (25.0+/-25.9 versus 5.9+/-12.9%, F=15.8, P< or =0.01; 52.6 versus
      18.4%, chi2=9.7, P< or =0.01; and 10.0 versus 57.1%, chi2=7.1, P< or =0.02,
      respectively). CONCLUSIONS: Implantation and pregnancy by ICSI is associated with
      morphological nuclear normalcy of sperm. Sperm with a morphologically abnormal
      nucleus usually have low fertility potential, but some with certain nuclear
      abnormalities may still be able to produce pregnancy following ICSI.

PMID- 15471931
TI  - Increased serum levels of nitric oxide metabolites among users of levonorgestrel
      releasing implants [corrected] a possible role in progestin-induced bleeding.
AB  - BACKGROUND: Nitric oxide (NO) is a potent angiogenic and vasodilator factor that
      could be involved in progestin-induced bleeding. This study aimed to assess
      possible changes in the serum levels of NO metabolites in users of levonorgestrel
      releasing implants (LNG-implants) [corrected] and to identify any correlation
      between some of their clinical characteristics and NO metabolite levels. METHODS:
      This cross-sectional study included 37 LNG-implants [corrected] users; a single 5
      ml venous blood was collected at different periods of [corrected] use. Women were
      divided into users with acceptable menstrual bleeding (n 5 13) [corrected] and
      those having abnormal bleeding patterns (n 5 24) [corrected] The controls are 13
      age-matched healthy women; they were fertile, had regular menstruation and did
      not use any contraceptive method in the previous 3 months. NO was determined by
      the evaluation of its oxidation products (nitrites and nitrates) where the
      nitrates were reduced to nitrites with cadmium filings; total serum
      concentrations of nitrites were measured by using the Griess reaction. RESULTS:
      The mean serum levels of NO metabolites were significantly higher in the LNG
      implants [corrected] users than in the controls (mean+/-SE) 34.9+/-11.3 versus
      6.1+/-1.5 mumol/l (P<0.001) [corrected] The mean serum levels of NO metabolites
      were significantly higher in the LNG-implants [corrected] users with abnormal
      bleeding patterns than in those with normal bleeding patterns (mean+/-SE) 41.3+/
      7.4 versus 23.2+/-5.8 mumol/l (P<0.001) [corrected] There was a positive
      correlation between NO levels and both prolonged spotting and heavy/prolonged
      bleeding days (P<0.001 and P<0.01, respectively) and negative correlation between
      NO levels with the duration of use and length of the menstrual cycle (P<0.05).
      CONCLUSION: The significantly increased serum levels of NO metabolites among LNG
      implants [corrected] users may primarily reflect an increase in its endometrial
      production, possibly secondary to its increased liberation by systemic vascular
      endothelium. This may result in enhanced endometrial angiogenesis and vascular
      dilatation which can induce and perpetuate abnormal excessive/prolonged uterine
      bleeding.

PMID- 15471932
TI  - Successful pregnancy following blastocyst cryopreservation using super-cooling
      ultra-rapid vitrification.
AB  - BACKGROUND: Blastocysts were cryopreserved by a new two-step ultra-rapid cooling
      in super-cooled liquid nitrogen (-205 degrees C). METHODS: There were 308 mouse
      blastocysts collected from fertile B6CBF1 mice and 249 human blastocysts
      collected from 51 couples treated with IVF. The blastocysts were super-cooled by
      a Vit-Master and cryoloops after treatment in 50 and 100% vitrification solution
      (VS) for 2 min and 30 s, respectively. The 100% VS was composed of 20% ethylene
      glycol, 20% dimethylsulphoxide and 0.5 mol/l sucrose in human tubular fluid
      medium with 20% human serum albumin. The embryos were warmed after treatment in
      0.25 and 0.125 mol/l sucrose for 2 and 3 min, respectively. The survival of
      embryos was observed after re-swell. RESULTS: The survival rate (SR) and hatching
      rate (HR) of mouse blastocysts in the super-cooled, the cryosolution-treated and
      control groups were not significantly different (SR, 87, 95.5 and 100%; HR, 50,
      33 and 44.6%, respectively; P>0.05). After 96 super-cooled human blastocysts were
      warmed, 60 survival blastocysts were transferred into 13 patients. The successful
      SR and pregnancy rate (PR) for the super-cooled blastocyst group were 77.1% (74
      out of 96) and 53.8% (seven out of 13). CONCLUSION: The ultra-rapid vitrification
      of blastocysts with a successful SR and PR could be used to replace classical
      slow cooling.

PMID- 15471933
TI  - Preimplantation genetic diagnosis for an insertional translocation carrier.
AB  - BACKGROUND: While preimplantation genetic diagnosis (PGD) is well established for
      carriers of reciprocal terminal translocations, reports on PGD for insertional
      translocation carriers are lacking. Here, we report on the PGD of an insertional
      translocation carrier with karyotype 46,XX,ins(14;2)(q21;q31q35). Due to the
      possibility of crossovers within the inserted region, rather than a single probe,
      four probes are required for proper embryo selection. METHODS: Probes were
      generated for PGD using fluorescence in situ hybridization and two PGD cycles.
      RESULTS: Analysis of 10 embryos revealed four embryos to be normal diploid. Two
      embryos were consistent with 3:1 segregation of the theoretical quadrivalent and
      one was consistent with 2:2 or 1:1 segregation. Furthermore, one embryo was
      mosaic abnormal and one remained without diagnosis. CONCLUSIONS: With increased
      acceptance of PGD, it is likely that more carriers of complex translocations will
      enter PGD programmes. The present results suggest that a careful genetic work-up
      of complex translocations is essential for proper embryo selection. While
      theoretical modelling may predict that quadrivalents will form during the meiosis
      of insertional translocations, experimental proof for the occurrence of
      quadrivalents is still lacking and more research on the meiotic process of both
      female and male insertional translocation carriers is warranted.

PMID- 15471934
TI  - Comparison of blastocyst transfer with or without preimplantation genetic
      diagnosis for aneuploidy screening in couples with advanced maternal age: a
      prospective randomized controlled trial.
AB  - BACKGROUND: It is generally accepted that the age-related increased aneuploidy
      rate is correlated with reduced implantation and a higher abortion rate.
      Therefore, advanced maternal age (AMA) couples are a good target group to assess
      the possible benefit of preimplantation genetic diagnosis for aneuploidy
      screening (PGD-AS) on the outcome after assisted reproductive technology (ART).
      METHODS: A prospective randomized controlled clinical trial (RCT) was carried out
      comparing the outcome after blastocyst transfer combined with PGD-AS using
      fluorescence in situ hybridization (FISH) for the chromosomes X, Y, 13, 16, 18,
      21 and 22 in AMA couples (aged > or =37 years) with a control group without PGD
      AS. From the 400 (200 for PGD-AS and 200 controls) couples that were allocated to
      the trial, an oocyte pick-up was performed effectively in 289 cycles (148 PGD-AS
      cycles and 141 control cycles). RESULTS: Positive serum HCG rates per transfer
      and per cycle were the same for PGD-AS and controls: 35.8% (19.6%) [%/per embryo
      transfer (per cycle)] and 32.2% (27.7%), respectively (NS). Significantly fewer
      embryos were transferred in the PGD-AS group than in the control group (P<0.001).
      The implantation rate (with fetal heart beat) was 17.1% in the PGD-AS group
      versus 11.5% in the control group (not significant; P=0.09). We observed a normal
      diploid status in 36.8% of the embryos. CONCLUSIONS: This RCT provides no
      arguments in favour of PGD-AS for improving clinical outcome per initiated cycle
      in patients with AMA when there are no restrictions in the number of embryos to
      be transferred.

PMID- 15471935
TI  - Human cumulus granulosa cell gene expression: a predictor of fertilization and
      embryo selection in women undergoing IVF.
AB  - BACKGROUND: A biochemical marker for embryo development would increase the chance
      of a successful pregnancy with IVF by optimizing oocyte and embryo selection, and
      allow fewer embryos to be transferred. In this study, we correlated cumulus
      granulosa cell gene expression of hyaluronic acid synthase 2 (HAS2),
      cyclooxygenase 2 (COX2; PTGS2) and gremlin (GREM1) with subsequent embryo
      development in search of a parameter for embryo selection. METHODS: Cumulus cell
      gene expression was determined prospectively on eight consecutive patients
      undergoing IVF with ICSI. Immediately following oocyte retrieval, the cumulus was
      stripped from the oocyte, and cumulus gene expression for PTGS2, HAS2 and GREM1
      was assessed using a one-step real-time quantitative RT-PCR assay. Oocyte
      quality, fertilization and embryo morphology were correlated to relative gene
      expression. RESULTS: Gene expression data were available on cumulus cells from
      108 oocytes that developed into 70 embryos (64.8% fertilization rate). Cumulus
      PTGS2, HAS2 and GREM1 expression was higher from oocytes that developed into
      higher quality embryos (grades 3, 4 and 5) compared with lower quality embryos
      (grades 1 and 2) (P<0.05, P<0.001 and P<0.001, respectively). HAS2 and GREM1
      expression was also higher from the cumulus surrounding oocytes that gave rise to
      higher grade embryos (P<0.001). The expression of PTGS2 and HAS2 was 6-fold
      higher, and that of GREM1 was 15-fold higher in cumulus yielding higher grade
      embryos versus lower grade embryos. CONCLUSION: PTGS2, HAS2 and GREM1 gene
      expression correlates to morphological and physiological characteristics and
      provides a novel approach to predict human embryo development. Ultimately, with
      better predictors of follicular and embryonic health, higher quality embryos can
      be selected and transferred, reducing higher order pregnancy rates.

PMID- 15471936
TI  - WAVE1, an A-kinase anchoring protein, during mammalian spermatogenesis.
AB  - BACKGROUND: Proper compartmentalization of signalling cascades is paramount to
      many intracellular activities during spermatogenesis and sperm function. In the
      present study we focus on the A-kinase-anchoring protein (AKAP) WAVE1, a member
      of the Wiskott-Aldrich syndrome (WASP) family of adaptor proteins, to study its
      localization throughout mammalian spermatogenesis. METHODS: Using transmission
      electron microscopy, immunocytochemistry and western blotting, we examined the
      distribution of WAVE1 and putative partners during mammalian spermatogenesis. The
      localization and association of PKA RII, the regulatory subunit II of protein
      kinase A, tyrosine kinase Abl, and small GTPase RAC1 were also explored. RESULTS:
      WAVE1 localization in spermatocytes and round spermatids coincided with Golgi
      apparatus distribution, whereas in elongated spermatids and testicular sperm
      WAVE1 localized to the mitochondrial sheath. Following epididymal passage, WAVE1
      was found exclusively on the mitochondrial sheath, suggesting that the protein
      may function in this region. WAVE1 and PKA RII co-localized along the
      mitochondrial sheath, PKA RII concentrates in the mid-piece, and RAC1 associated
      with the post-acrosomal region and the connecting piece. The distribution of
      WAVE1, PKA RII and RAC1 is conserved in mature mouse, bull, baboon and human
      sperm. CONCLUSIONS: The data support the possibility of a functional signalling
      unit established by WAVE1 and its associated proteins in the mid-piece of
      maturing sperm.

PMID- 15471937
TI  - Expression of cystic fibrosis transmembrane conductance regulator in human
      endometrium.
AB  - BACKGROUND: As a cAMP-regulated Cl- channel, cystic fibrosis transmembrane
      conductance regulator (CFTR) plays a critical role in the active secretion of
      electrolytes and fluid in epithelial cells. Women with CFTR gene mutations are
      less fertile, generally assumed to be due to cervical factors. However, there is
      little known about CFTR protein expression in human endometrium and its possible
      roles in reproduction. METHODS AND RESULTS: CFTR protein and mRNA levels in human
      endometrium were analysed using immunohistochemical and in situ hybridization
      methods, respectively. Significant expression of CFTR protein was only seen in
      the glandular cells from late proliferative to all secretory phases, consistent
      with western blot analysis. High levels of CFTR mRNA were present only around the
      ovulatory period. In cultured glandular cells, the production of CFTR protein and
      mRNA was stimulated by estradiol and inhibited by progesterone. A forskolin
      activated Cl- current in endometrial epithelial cells with a linear I-V
      relationship was detected by the whole-cell patch-clamp technique. CONCLUSIONS:
      (i) CFTR mRNA and protein were localized in human endometrial epithelial cells
      and the amounts varied in a cyclic manner; (ii) CFTR expression in cultured
      glandular cells was up- and downregulated by estradiol and progesterone,
      respectively; and (iii) CFTR in human endometrium functions as a cAMP-activated
      Cl- channel.

PMID- 15471938
TI  - Association of estradiol levels on the day of hCG administration and pregnancy
      achievement in IVF: a systematic review.
AB  - BACKGROUND: Evaluation of the association between estradiol (E2) levels on the
      day of hCG administration and pregnancy achievement in IVF has so far yielded
      conflicting results. The purpose of the present study was to systematically
      review the above association in cycles down-regulated with GnRH analogues.
      METHODS: Literature search was performed using Medline, Embase (1978-2004) and
      the Cochrane Library. Additionally, references of retrieved articles were hand
      searched. Only full articles published in peer-reviewed medical journals were
      considered for analysis. RESULTS: All the eligible studies (n=9) involved the use
      of GnRH agonists and were retrospective. Two studies (including 191 patients)
      suggested that the higher the E2 levels on the day of hCG administration, the
      higher the probability of pregnancy. However, five studies (including 1875
      patients), did not support an association between E2 levels on the day of hCG
      administration and pregnancy rates. Moreover, two of the studies including (1286
      patients) suggested that high E2 levels on the day of hCG administration are
      associated with a decreased probability of pregnancy. If we consider only studies
      in which criteria used for administering hCG include follicular development but
      not E2 levels (including 2687 patients), there is no study suggesting a positive
      association between E2 levels on the day of hCG administration and pregnancy
      achievement. CONCLUSIONS: Currently there is no high-quality evidence to support
      or deny the value of E2 determination on the day of hCG administration for
      pregnancy achievement in IVF cycles, where pituitary down-regulation is performed
      with GnRH agonists. Existing retrospective studies suggest that there is no
      positive association. However, in order to arrive at recommendations for clinical
      practice, there is a need to perform well-designed prospective studies in both
      agonist and antagonist cycles.

PMID- 15471939
TI  - Uterine Doppler studies: technology driven data, or answers to our
      pathophysiological queries?

PMID- 15471940
TI  - Olfactometric and rhinomanometric outcomes in post-menopausal women treated with
      hormone therapy: a prospective study.
AB  - BACKGROUND: The aim of this prospective study was to evaluate the effects of
      hormone therapy (HT) on olfactory sensitivity in post-menopausal women. METHODS:
      Forty-six naturally post-menopausal women underwent rhinomanometric and
      olfactometric measurements to compare nasal airflow resistance values and
      olfactometric thresholds during the eighth month of HT treatment with baseline
      levels prior to starting HT. Eighteen women used an oral HT regimen, and twenty
      eight women used transdermal patch HT. RESULTS: Rhinomanometric values during HT
      were statistically differ from those at baseline (P < 0.001). Olfactometric
      threshold data indicated a higher sensitivity during the HT treatment than at
      baseline (P < 0.001). Finally, no statistically significant difference was
      observed among women using oral or patch HT administration on rhinomanometric and
      olfactometric values. CONCLUSIONS: Our study demonstrates that 8 months of
      treatment with estrogen and progestogens in HT preparations has an effect on
      nasal airflow resistance and the olfactory thresholds to odours. We believe that
      estrogens could influence neuronal plasticity, and the neuronal conduction time
      into the olfactory system. Our findings confirm that gonadal steroids such as
      estrogen have an influence on non-genital targets; this relationship might have a
      beneficial impact on sensorineural communication and emotional behaviour.

PMID- 15471941
TI  - Modified natural cycle for IVF does not offer a realistic chance of parenthood in
      poor responders with high day 3 FSH levels, as a last resort prior to oocyte
      donation.
AB  - BACKGROUND: The purpose of this study was to evaluate the use of the modified
      natural cycle (MNC) for IVF in poor responders as a last resort prior to oocyte
      donation. METHODS: Thirty-two patients with a regular menstrual cycle, FSH levels
      on day 3 of the cycle >12 IU/l and one or more failed IVF cycles with five or
      fewer cumulus-oocyte complexes (COCs) retrieved were included in this prospective
      study. Recombinant FSH 100 IU and GnRH antagonist 0.25 mg/day were started
      concomitantly when a follicle with a mean diameter of 14 mm was present at
      ultrasound. HCG 10 000 IU was administered as soon as the mean follicular
      diameter was > or =16 mm. RESULTS: Twenty-five out of 78 cycles performed (32.1%)
      did not result in oocyte retrieval. In nine out of 53 cycles (16.9%) in which
      oocyte retrieval was performed, no COCs were retrieved. Following fertilization,
      embryo transfer was performed in 19 out of 44 cycles in which COCs were retrieved
      (43.2%). No ongoing pregnancy was achieved in 78 MNCs (0.0%; 95% confidence
      interval 0.0-4.7). CONCLUSIONS: MNC does not offer a realistic chance of
      parenthood in patients with high levels of FSH on day 3 of the cycle and previous
      poor response to ovarian stimulation, when offered as a last resort prior to
      oocyte donation.

PMID- 15471942
TI  - Regulation of progesterone levels during pregnancy and parturition by signal
      transducer and activator of transcription 5 and 20alpha-hydroxysteroid
      dehydrogenase.
AB  - The two highly related signal transducers and activators of transcription
      (Stats), Stat5a and Stat5b, are major mediators of prolactin signaling in both
      the mammary gland and in the ovary. Deficiencies in Stat5b, or in both Stat5a and
      Stat5b, result in loss of pregnancy during midgestation and are correlated with
      an increase in ovarian 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) and a
      decrease in serum progesterone, which normally declines only immediately before
      parturition. To determine the relative contribution of 20alpha-HSD to
      progesterone metabolism and Stat5 function during pregnancy and parturition, we
      created a 20alpha-HSD-deficient strain of mice by gene disruption. Mice deficient
      for 20alpha-HSD sustain high progesterone levels and display a delay in
      parturition of several days demonstrating that 20alpha-HSD regulates parturition
      downstream of the prostaglandin F2alpha receptor in an essential and nonredundant
      manner. Moreover, 20alpha-HSD deficiency partially corrected the abortion of
      pregnancies associated with Stat5b deficiency, supporting the concept that
      prolactin activation of Stat5b is important in suppressing 20alpha-HSD gene
      expression and thereby allowing the maintenance of progesterone levels that are
      required to sustain pregnancy.

PMID- 15471943
TI  - The HeLa cell glucagon-like peptide-2 receptor is coupled to regulation of
      apoptosis and ERK1/2 activation through divergent signaling pathways.
AB  - Glucagon-like peptide-2 (GLP-2) regulates proliferative and cytoprotective
      pathways in the intestine; however GLP-2 receptor (GLP-2R) signal transduction
      remains poorly understood, and cell lines that express the endogenous GLP-2R have
      not yet been isolated. We have now identified several expressed sequence tags
      from human cervical carcinoma cDNA libraries that correspond to GLP-2R nucleotide
      sequences. GLP-2R mRNA transcripts were detected by RT-PCR in two human cervical
      carcinoma cell lines, including HeLa cells. GLP-2 increased cAMP accumulation and
      activated ERK1/2 in HeLa cells transiently expressing the cloned human HeLa cell
      GLP-2R cDNA. However, the GLP-2R-induced activation of ERK1/2 was not mediated
      through Galphas, adenylyl cyclase, or transactivation of the epidermal growth
      factor receptor, but was pertussis toxin sensitive, inhibited by dominant
      negative Ras, and dependent on betagamma-subunits. GLP-2 also induced a
      significant increase in bromodeoxyuridine incorporation that was blocked by
      dominant negative Ras. Furthermore, GLP-2 inhibited HeLa cell apoptosis induced
      by LY294002 in a protein kinase A-dependent, but ERK-independent, manner. These
      findings demonstrate that the HeLa cell GLP-2R differentially signals through
      both Galphas/cAMP- and Gi/Go-dependent pathways, illustrating for the first time
      that the GLP-2R is capable of coupling to multiple heterotrimeric G proteins
      defining distinct GLP-2R-dependent biological actions.

PMID- 15471944
TI  - Inhibition of Ca2+-independent phospholipase A2 results in insufficient insulin
      secretion and impaired glucose tolerance.
AB  - Islet Ca2+-independent phospholipase A2 (iPLA2) is postulated to mediate insulin
      secretion by releasing arachidonic acid in response to insulin secretagogues.
      However, the significance of iPLA2 signaling in insulin secretion in vivo remains
      unexplored. Here we investigated the physiological role of iPLA2 in beta-cell
      lines, isolated islets, and mice. We showed that small interfering RNA-specific
      silencing of iPLA2 expression in INS-1 cells significantly reduced insulin
      secretory responses of INS-1 cells to glucose. Immunohistochemical analysis
      revealed that mouse islet cells expressed significantly higher levels of iPLA2
      than pancreatic exocrine acinar cells. Bromoenol lactone (BEL), a selective
      inhibitor of iPLA2, inhibited glucose-stimulated insulin secretion from isolated
      mouse islets; this inhibition was overcome by exogenous arachidonic acid. We also
      showed that iv BEL administration to mice resulted in sustained hyperglycemia and
      reduced insulin levels during glucose tolerance tests. Clamp experiments
      demonstrated that the impaired glucose tolerance was due to insufficient insulin
      secretion rather than decreased insulin sensitivity. Short-term administration of
      BEL to mice had no effect on fasting glucose levels and caused no apparent
      pathological changes of islets in pancreas sections. These results unambiguously
      demonstrate that iPLA2 signaling plays an important role in glucose-stimulated
      insulin secretion under physiological conditions.

PMID- 15471946
TI  - The epithelial glucocorticoid receptor is required for the normal timing of cell
      proliferation during mammary lobuloalveolar development but is dispensable for
      milk production.
AB  - Glucocorticoids have been shown to influence mammary gland function in vivo and
      to stimulate milk protein gene expression in vitro. Here, we describe the
      generation and analysis of a mouse model to study glucocorticoid receptor (GR,
      NR3C1) function in mammary epithelial cells. Using the Cre-loxP system, mutant
      mice were obtained in which the GR gene is specifically deleted in epithelial
      cells during lobuloalveolar development, leading to a complete loss of epithelial
      GR at the onset of lactation. Mice harboring the mammary-epithelial-specific GR
      mutation are able to nurse their litters until weaning. During pregnancy,
      however, GR deficiency delays lobuloalveolar development, leading to an
      incomplete epithelial penetration of the mammary fat pad that persists throughout
      lactation. We identified a reduced cell proliferation during lobuloalveolar
      development as reason for this delay. This reduction is compensated for by
      increased epithelial proliferation after parturition in the mutant glands. During
      lactation, GR-deficient mammary epithelium is capable of milk production and
      secretion. The expression of two milk proteins, namely whey acidic protein and
      beta-casein, during lactation was not critically affected in the absence of GR.
      We conclude that GR function is not essential for alveolar differentiation and
      milk production, but influences cell proliferation during lobuloalveolar
      development.

PMID- 15471945
TI  - LBP proteins modulate SF1-independent expression of P450scc in human placental
      JEG-3 cells.
AB  - The cholesterol side-chain cleavage enzyme, P450scc, initiates biosynthesis of
      all steroid hormones. Adrenal and gonadal P450scc expression requires
      steroidogenic factor-1 (SF1), but P450scc expression in human placental JEG-3
      cells utilizes an SF1-independent element at -155/-131 that is inactive in
      adrenals and gonads. We previously cloned two transcription factors, long
      terminal repeat binding protein (LBP)-1b and LBP-9, from JEG-3 cells. In
      transient transfection assays, LBP-1b activated the -155/-131 element whereas LBP
      9 suppressed its LBP-1b-stimulated expression. To assess the roles of these
      factors on the intact P450scc gene, we stably expressed LBP-1b or LBP-9 in JEG-3
      cells. All cell lines stably expressing a fusion protein of LBP-1b and enhanced
      green fluorescent protein increased P450scc expression, but cell lines stably
      expressing LBP-9 fused to enhanced green fluorescent protein either increased or
      decreased P450scc expression. 8-Br-cAMP induced endogenous LBP-9, but not LBP-1b
      expression. Glutathione-S-transferase pull-down assays showed that LBP-1b and LBP
      9 can dimerize with themselves and with each other; LBP-1b residues 300-540 and
      LBP-9 residues 300-479 were required for dimer formation. Glutathione-S
      transferase pull-down assays, bandshifts, and transient transfection assays
      showed that TReP-132 (another factor that can bind to -155/-131) does not
      interact with either LBP-1b or LBP-9, or influence their ability to induce or
      suppress transcription from the -155/-131 element. Gal4 transactivation assays
      showed that transcriptional repression activity by LBP-9 requires residues 100
      200. RNAi interference of either LBP-1b or LBP-9 mRNAs decreased P450scc
      expression. LBP-1b is an important SF1-independent transcriptional activator
      stimulating P450scc expression in human placental JEG-3 cells, whereas LBP-9
      modulates the action of LBP-1b, exerting both positive and negative effects.

PMID- 15471947
TI  - Evidence that an isoform of calpain-10 is a regulator of exocytosis in pancreatic
      beta-cells.
AB  - Calpain-10 (CAPN10) is the first type 2 diabetes susceptibility gene to be
      identified through a genome scan, with polymorphisms being associated with
      altered CAPN10 expression. Functional data have been hitherto elusive, but we
      report here a corresponding increase between CAPN10 expression level and
      regulated insulin secretion. Pancreatic beta-cell secretory granule exocytosis is
      mediated by the soluble N-ethylmaleimide-sensitive fusion protein attachment
      receptor protein complex of synaptosomal-associated protein of 25 kDa (SNAP-25),
      syntaxin 1, and vesicle-associated membrane protein 2. We report, for the first
      time, direct binding of a calpain-10 isoform with members of this complex.
      Furthermore, SNAP-25 undergoes a Ca2+-dependent partial proteolysis during
      exocytosis, with calpain protease inhibitor similarly suppressing both insulin
      secretion and SNAP-25 proteolysis. Based upon these findings, we postulate that
      an isoform of calpain-10 is a Ca2+-sensor that functions to trigger exocytosis in
      pancreatic beta-cells.

PMID- 15471948
TI  - The constitutive mobilization of bone marrow-repopulating cells into the
      peripheral blood in idiopathic myelofibrosis.
AB  - Idiopathic myelofibrosis (IM) is characterized by the constitutive mobilization
      of CD34(+) cells. IM peripheral blood (PB) CD34(+) cells had a reduced cloning
      efficiency and a lower frequency of cobblestone areas compared with normal
      granulocyte colony-stimulating factor (G-CSF)-mobilized PB CD34(+) cells. IM
      CD34(+) cells engrafted nonobese diabetic/severe combined immunodeficient
      (NOD/SCID) mice, demonstrating that they contain bone marrow (BM)-repopulating
      cells. G-CSF-mobilized CD34(+) cells produced multiple hematopoietic lineages
      within the NOD/SCID mice with a predominance of CD19(+) cells. By contrast, IM
      CD34(+) cells produced predominantly CD33(+) cells, increased numbers of CD41(+)
      cells, but fewer CD19(+) cells. Transcriptional clonality assays of the engrafted
      human IM cells demonstrated their clonal origin. CD34(+) cells from one patient
      isolated prior to leukemic transformation were capable of generating acute
      leukemia in NOD/SCID mice. The engrafted human cells exhibited the same abnormal
      karyotype as primary cells in a portion of the population. These findings
      demonstrate that BM-repopulating cells and more differentiated progenitor cells
      are constitutively mobilized into the PB in IM, and that their differentiation
      program is abnormal. In addition, the NOD/SCID model may be useful in gaining an
      understanding of the events occurring during the transition of IM to acute
      leukemia.

PMID- 15471949
TI  - Heparanase promotes the spontaneous metastasis of myeloma cells to bone.
AB  - Although widespread skeletal dissemination is a critical step in the progression
      of myeloma, little is known regarding mechanisms that control metastasis of this
      cancer. Heparanase-1 (heparanase), an enzyme that cleaves heparan sulfate chains,
      is expressed at high levels in some patients with myeloma and promotes metastasis
      of some tumor types (eg, breast, lymphoma). Using a severe combined
      immunodeficient (SCID) mouse model, we demonstrate that enhanced expression of
      heparanase by myeloma cells dramatically up-regulates their spontaneous
      metastasis to bone. This occurs from primary tumors growing subcutaneously and
      also from primary tumors established in bone. Interestingly, tumors formed by
      subcutaneous injection of cells metastasize not only to bone, but also to other
      sites including spleen, liver, and lung. In contrast, tumors formed by injection
      of cells directly into bone exhibit a restricted pattern of metastasis that
      includes dissemination of tumor to other bones but not to extramedullary sites.
      In addition, expression of heparanase by myeloma cells (1) accelerates the
      initial growth of the primary tumor, (2) increases whole-body tumor burden as
      compared with controls, and (3) enhances both the number and size of microvessels
      within the primary tumor. These studies describe a novel experimental animal
      model for examining the spontaneous metastasis of bone-homing tumors and indicate
      that heparanase is a critical determinant of myeloma dissemination and growth in
      vivo.

PMID- 15471950
TI  - Activation of the p70 S6 kinase by all-trans-retinoic acid in acute promyelocytic
      leukemia cells.
AB  - Although the mechanisms by which all-trans-retinoic acid (RA) regulates gene
      transcription are well understood, very little is known on the signaling events
      regulating RA-dependent initiation of mRNA translation. We examined whether the
      mammalian target of rapamycin (mTOR)/p70 S6 kinase pathway is activated by RA. RA
      treatment of sensitive cell lines resulted in phosphorylation/activation of mTOR
      and downstream induction of p70 S6 kinase activity. Such
      phosphorylation/activation of p70 S6 kinase was inducible in primary acute
      promyelocytic leukemia (APL) blasts and RA-sensitive NB-4 cells, but was
      defective in an NB-4 variant cell line (NB-4.007/6) that is resistant to the
      biologic effects of RA. The RA-dependent activation of p70 S6 kinase was also
      phosphatidylinositol 3' kinase (PI3'K)-dependent, and resulted in downstream
      phosphorylation of the S6 ribosomal protein on Ser235/236 and Ser240/244, events
      important for initiation of translation for mRNAs with oligopyrimidine tracts in
      their 5' untranslated region. RA treatment of leukemia cells also resulted in an
      mTOR-mediated phosphorylation of the 4E-BP1 repressor of mRNA translation, to
      induce its deactivation and dissociation from the eukaryotic initiation factor-4E
      (eIF-4E) complex. Altogether, these findings provide evidence for the existence
      of a novel RA-activated cellular pathway that regulates cap-dependent
      translation, and strongly suggest that this cascade plays a role in the induction
      of retinoid responses in APL cells.

PMID- 15471951
TI  - The pathophysiologic role of VEGF in hematologic malignancies: therapeutic
      implications.
AB  - Besides its role as an essential regulator of physiologic and pathologic
      angiogenesis, vascular endothelial growth factor (VEGF) triggers growth,
      survival, and migration of leukemia and multiple myeloma cells; plays a pivotal
      role in hematopoiesis; inhibits maturation of dendritic cells; and increases
      osteoclastic bone-resorbing activity as well as osteoclast chemotaxis.
      Dysregulation of VEGF expression and signaling pathways therefore plays an
      important role in the pathogenesis and clinical features of hematologic
      malignancies, in particular multiple myeloma. Direct and indirect targeting of
      VEGF and its receptors therefore may provide a potent novel therapeutic approach
      to overcome resistance to therapies and thereby improve patient outcome.

PMID- 15471952
TI  - Differential regulation of virus-specific T-cell effector functions following
      activation by peptide or innate cytokines.
AB  - Robust CD8(+) T-cell activation is vital for the recovery from many viral
      infections and is orchestrated via the integration of signals delivered through
      surface molecules, including the T-cell antigen receptors (TcRs) and cytokine
      receptors. Little is known about how virus-specific T cells interpret sequential
      or combined stimulation through these receptors, which must undoubtedly occur in
      vivo during antiviral immune responses. When measured in real time, peptide
      antigen and the cytokines, interleukin 12 (IL-12) and IL-18, independently
      regulate the on/off kinetics of protective (interferon gamma, tumor necrosis
      factor alpha) and immunomodulatory (IL-2, CD40L) cytokine production by activated
      T cells and memory T cells. The remarkable differences in effector functions
      elicited by innate or adaptive signals (IL-12/ IL-18 or peptide, respectively)
      illustrate the complex and stringent regulation of cytokine expression by CD8(+)
      T cells. Together, these results indicate how antiviral T cells incorporate
      multiple signals from their local microenvironment and tailor their cytokine
      responses accordingly.

PMID- 15471953
TI  - Immune regulatory activity of CD34+ progenitor cells: evidence for a deletion
      based mechanism mediated by TNF-alpha.
AB  - Previous studies suggest that cells within the CD34(+) hematopoietic stem cell
      compartment are endowed with immune regulatory activity. Furthermore, it is
      possible to expand the human regulatory cells upon short-term culture of purified
      CD34+ cells with an early-acting cytokine cocktail. We now show that addition of
      anti-CD28, anti-CD2, interleukin-2 (IL-2), anti-IL-10, or IL-12 to the bulk mixed
      lymphocyte reaction (MLR) cannot reverse the inhibitory activity of the CD34+
      cells, ruling out anergy-based mechanisms or mechanisms involving Th1-Th2
      skewing. Furthermore, phenotyping of cells present after addition of CD34+ cells
      to the bulk MLR ruled out potential induction of plasmacytoid dendritic
      precursors, known to be endowed with regulatory activity. In contrast, the
      inhibitory activity of CD34+ cells could be reversed by adding the caspase
      inhibitor BD-FMK to the bulk MLR, indicating a deletion-based mechanism. The
      deletion can be inhibited by anti-tumor necrosis factor-alpha (anti-TNF-alpha)
      and not by anti-transforming growth factor-beta (anti-TGF-beta), suggesting a
      potential role for TNF-alpha in the regulatory activity of CD34+ cells.

PMID- 15471954
TI  - Annexin A2 mediates endothelial cell activation by antiphospholipid/anti-beta2
      glycoprotein I antibodies.
AB  - Patients with antiphospholipid antibodies (APLAs) are at increased risk for
      arterial and venous thrombosis. Many APLAs associated with these events react
      with beta2 glycoprotein I (beta2GPI), and endothelial cell reactive antibodies
      that activate endothelial cells in a beta2GPI-dependent manner occur commonly in
      these patients. We previously reported that beta2GPI binds with high affinity to
      annexin A2 on the endothelial surface, though the relevance of this interaction
      to APLA/anti-beta2GPI antibody-induced endothelial activation has not been
      determined. In this report, we confirm that anti-beta2GPI antibodies activate
      endothelial cells in the presence of beta2GPI, and demonstrate that anti-annexin
      A2 antibodies directly cause endothelial cell activation of a similar magnitude
      and with a similar time course. Moreover, bivalent anti-annexin A2 F(ab')2
      fragments also caused endothelial cell activation, whereas monomeric Fab
      fragments not only did not cause activation, but blocked activation induced by
      anti-annexin A2 antibodies and F(ab')2 fragments, as well as that caused by anti
      beta2GPI antibodies in the presence of beta2GPI. These observations suggest a
      novel pathway for endothelial activation induced by APLA/anti-beta2GPI antibodies
      that is initiated by cross-linking or clustering of annexin A2 on the endothelial
      surface.

PMID- 15471955
TI  - Fibromodulin as a novel tumor-associated antigen (TAA) in chronic lymphocytic
      leukemia (CLL), which allows expansion of specific CD8+ autologous T lymphocytes.
AB  - Fibromodulin (FMOD) was shown to be highly overexpressed in chronic lymphocytic
      leukemia (CLL) cells compared with normal B lymphocytes by gene expression
      profiling. Therefore FMOD might serve as potential tumor-associated antigen (TAA)
      in CLL, enabling expansion of FMOD-specific T cells. In CLL samples derived from
      16 different patients, high expression of FMOD by real-time reverse transcriptase
      polymerase chain reaction (RT-PCR) was detectable in contrast to normal B
      lymphocytes. We used unpulsed native CLL cells and CD40 ligand (CD40L)-stimulated
      CLL cells as antigen-presenting cells (APCs) to expand autologous T cells from 13
      patients. The number of T cells during 4 weeks of in vitro culture increased 2-
      to 3.5-fold and the number of T cells recognizing FMOD peptides bound to HLA-A2
      dimers increased 10-fold. The expanded T cells also were able to secrete
      interferon-gamma (IFN-gamma) upon recognition of the antigen demonstrated by IFN
      gamma ELISPOT assays. T cells not only recognized HLA-A2-binding FMOD peptides
      presented by transporter-associated with antigen-processing (TAP)-deficient T2
      cells, but also FMOD overexpressing autologous CLL cells in an HLA-A2-restricted
      manner. In summary, FMOD was shown for the first time to be naturally processed
      and presented as TAA in primary CLL cells, enabling the expansion of autologous
      tumor-specific T cells.

PMID- 15471956
TI  - Overexpression of a cell adhesion molecule, TSLC1, as a possible molecular marker
      for acute-type adult T-cell leukemia.
AB  - Adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type 1 (HTLV-1)
      infection, occurs in 2% to 4% of the HTLV-1 carriers with a long latent period,
      suggesting that additional alterations participate in the development of ATL. To
      characterize and identify novel markers of ATL, we examined the expression
      profiles of more than 12 000 genes in 8 cases of acute-type ATL using microarray.
      One hundred ninety-two genes containing interleukin 2 (IL-2) receptor alpha were
      up-regulated more than 2-fold compared with CD4(+) and CD4(+)CD45RO(+) T cells,
      and tumor suppressor in lung cancer 1 (TSLC1), caveolin 1, and prostaglandin D2
      synthase showed increased expression of more than 30-fold. TSLC1 is a cell
      adhesion molecule originally identified as a tumor suppressor in the lung but
      lacks its expression in normal or activated T cells. We confirmed ectopic
      expression of the TSLC1 in all acute-type ATL cells and in 7 of 10 ATL- or HTLV-1
      infected T-cell lines. Introduction of TSLC1 into a human ATL cell line ED
      enhanced both self-aggregation and adhesion ability to vascular endothelial
      cells. These results suggested that the ectopic expression of TSLC1 could provide
      a novel marker for acute-type ATL and may participate in tissue invasion, a
      characteristic feature of the malignant ATL cells.

PMID- 15471957
TI  - Ephrin B2 expression in Kaposi sarcoma is induced by human herpesvirus type 8:
      phenotype switch from venous to arterial endothelium.
AB  - Kaposi sarcoma (KS) is an angioproliferative tumor derived from endothelial cells
      in which tumor cells form aberrant vascular structures. Ephrin B2 and ephrin B4
      (EphB4) are artery- and vein-specific proteins, respectively, with critical roles
      in vessel maturation. We investigated whether the disorganized KS vasculature was
      due to unbalanced expression of ephrin B2 and EphB4. Secondly, we wished to
      determine if human herpesvirus type 8 (HHV-8), the viral agent associated with
      KS, regulates ephrin B2 and EphB4. An arterial phenotype was observed in KS
      tissue and cell lines, as shown by abundant expression of ephrin B2 with little
      or no EphB4. Infection of venous endothelial cells with HHV-8 resulted in a
      phenotype switch from EphB4 to ephrin B2, similar to that seen with vascular
      endothelial growth factor (VEGF). The HHV-8 effect on ephrin B2 expression was
      reproduced with the HHV-8-specific viral G-protein-coupled receptor. We also
      showed that ephrin B2 expression is required for KS cell viability by knock down
      with siRNA. KS is the first example of a human tumor with a predominantly
      arterial phenotype. This predominance can be attributed to expression of HHV-8
      proteins and their downstream effects. Ephrin B2 is thus an important novel
      factor in KS biology and a potential target for therapy.

PMID- 15471958
TI  - Transformation of Skeletal Muscle from Fast- to Slow-Twitch during Acquisition of
      Cold Tolerance in the Chick.
AB  - Although birds lack brown adipose tissue, a thermogenic organ found in mammals,
      they possess other thermogenic mechanisms. In the current studies, we examined
      the molecular mechanisms of avian thermogenesis by studying how chicks acquire
      cold tolerance. We found that the acquisition of cold tolerance corresponded with
      an increase in the redness of the skeletal muscle, suggesting an increase in slow
      twitch muscle fiber. This was confirmed by histological analysis. In addition, in
      chicks acquiring cold tolerance, there was an enhanced expression of the chicken
      homologue of peroxisome proliferator-activated receptor-gamma coactivator-1alpha,
      a protein involved in adaptive thermogenesis in mammalian brown adipose tissue
      and in slow-twitch fiber formation in mammalian skeletal muscle. Subtraction and
      differential display techniques further showed that, when chicks acquired cold
      tolerance, the expression of genes associated with slow-twitch fibers increased,
      whereas those associated with fast-twitch fibers decreased. There was also an
      enhanced expression of mitochondrial oxidative genes. Together, these results
      suggest that transformation of skeletal muscle fiber from fast-twitch to slow
      twitch is involved in the acquisition of thermogenesis in chicks.

PMID- 15471959
TI  - Transgenic mice overexpressing des-acyl ghrelin show small phenotype.
AB  - Ghrelin, a 28-amino acid acylated peptide, displays strong GH-releasing activity
      in concert with GHRH. The fatty acid modification of ghrelin is essential for the
      actions, and des-acyl ghrelin, which lacks the modification, has been assumed to
      be devoid of biological effects. Some recent reports, however, indicate that des
      acyl ghrelin has effects on cell proliferation and survival. In the present
      study, we generated two lines of transgenic mice bearing the preproghrelin gene
      under the control of chicken beta-actin promoter. Transgenic mice overexpressed
      des-acyl ghrelin in a wide variety of tissues, and plasma des-acyl ghrelin levels
      reached 10- and 44-fold of those in control mice. They exhibited lower body
      weights and shorter nose-to-anus lengths, compared with control mice. The serum
      GH levels tended to be lower, and the serum IGF-I levels were significantly lower
      in both male and female transgenic mice than control mice. The responses of GH to
      administered GHRH were normal, whereas those to administered ghrelin were
      reduced, especially in female transgenic mice, compared with control mice. These
      data suggest that overexpressed des-acyl ghrelin may modulate the GH-IGF-I axis
      and result in small phenotype in transgenic mice.

PMID- 15471960
TI  - Pdx-1 is not sufficient for repression of proglucagon gene transcription in islet
      or enteroendocrine cells.
AB  - Pdx-1 plays a key role in the development of the pancreas and the control of
      islet gene transcription and has also been proposed as a dominant regulator of
      the alpha- vs. beta-cell phenotype via extinction of proglucagon expression. To
      ascertain the relationship between Pdx-1 and proglucagon gene expression, we
      examined the effect of enhanced pdx-1 expression on proglucagon gene expression
      in murine islet alphaTC-1 and GLUTag enteroendocrine cells. Although adenoviral
      transduction increased the levels of pdx-1 mRNA transcripts and nuclear Pdx-1
      protein, overexpression of pdx-1 did not repress endogenous proglucagon gene
      expression in alphaTC-1 or GLUTag cells or murine islets. Immunohistochemical
      analysis of cells transduced with Ad-pdx-1 demonstrated multiple individual islet
      or enteroendocrine cells exhibiting both nuclear Pdx-1 and cytoplasmic glucagon
      like peptide-1 immunopositivity. The failure of pdx-1 to inhibit endogenous
      proglucagon gene expression was not attributable to defects in Pdx-1 nuclear
      translocation or DNA binding as demonstrated using Western blotting and EMSA
      analyses. Furthermore, Ad-pdx-1 transduction did not repress proglucagon promoter
      activity in alphaTC-1 or GLUTag cells. Taken together, these findings demonstrate
      that pdx-1 alone is not sufficient for specification of the hormonal phenotype or
      extinction of proglucagon gene expression in islet or enteroendocrine cells.

PMID- 15471961
TI  - 17beta-estradiol-dependent activation of signal transducer and activator of
      transcription-1 in human fetal osteoblasts is dependent on Src kinase activity.
AB  - Estrogen is essential for normal growth and remodeling of bone. Although the
      mechanism of estrogen action on bone cells has been widely investigated, the full
      spectrum of signal transduction pathways activated by estrogen is unknown. In
      this report, we investigate the effects of the gonadal hormone 17beta-estradiol
      on the regulation of signal transducer and activator of transcription-1 (Stat1)
      protein in cultured human fetal osteoblast cells, devoid of the classical
      estrogen receptors (ERs). 17beta-estradiol (10 nM) led to rapid (within 15 min)
      activation of Stat1 protein as indicated by increases in tyrosine phosphorylation
      and DNA binding activity. Also, 17beta-estradiol increased gamma-activated
      sequence-dependent transcription in transient transfection assays, suggesting an
      increase in Stat protein-dependent transcription. Estrogen-dependent Stat1
      activation was blocked in cells that transiently express dominant-negative Stat1
      mutant protein. Activation of Stat1 by 17beta-estradiol was not inhibited by ER
      antagonist ICI 182,780, providing further evidence that it is not dependent on
      classical ERs. 17beta-Estradiol induced rapid (within 15 min) Stat1
      phosphorylation and stimulated gamma-activated sequence-dependent transcription
      in ER-negative breast cancer cells, indicating that these results are not unique
      to bone cells. The rapid estrogenic effect involving the phosphorylation and
      activation of Stat1 was blocked in the presence of Src family kinase inhibitor
      PP2; activated Stat1 was associated with Src protein in estrogen-treated cells.
      These findings indicate the requirement for Src kinase pathways in estrogen
      mediated Stat1 activation. Thus, the ER-independent activation of Stat1 in 17beta
      estradiol-treated osteoblast and breast cancer cells may partially mediate the
      actions of estrogen on target cells.

PMID- 15471962
TI  - Expression of the ghrelin axis in the mouse: an exon 4-deleted mouse proghrelin
      variant encodes a novel C terminal peptide.
AB  - Ghrelin, an n-octanoylated 28-amino-acid peptide capable of inducing GH secretion
      and food intake in humans and rats, is the endogenous ligand for the GH
      secretagogue receptor (GHS-R). Here we describe the expression and tissue
      distribution of the ghrelin/GHS-R axis in the mouse. We also report for the first
      time the identification of a novel mouse ghrelin mRNA variant in which there is a
      complete deletion of exon 4. Translation of this variant mRNA yields a protein
      containing ghrelin and an alternative C-terminal domain with a unique C-terminal
      peptide sequence. RT-PCR with primers specific for mouse ghrelin was used to
      demonstrate the mRNA expression of the full preproghrelin transcript and the exon
      4-deleted variant in multiple mouse tissues. Real-time PCR was also employed to
      quantitate mRNA expression of ghrelin, the novel isoform and a previously
      reported ghrelin gene variant, ghrelin gene-derived transcript. We also
      demonstrated the tissue expression of the functional GHS-R in the mouse.
      Immunohistochemistry, employing antibodies raised against the mature human n
      octanoylated ghrelin peptide and the putative C-terminal peptide encoded by the
      exon 4-deleted proghrelin variant, was used to demonstrate protein expression of
      ghrelin and the variant in multiple mouse tissues including stomach, kidney, and
      reproductive tissues. The coexpression of ghrelin and its receptor in a wide
      range of murine tissues suggests varied autocrine/paracrine roles for these
      peptides. Exon 4-deleted proghrelin, a novel mouse proghrelin isoform with a
      unique C-terminal peptide sequence, is also widely expressed in the mouse and
      thus may possess biological activity in these tissues.

PMID- 15471964
TI  - Low-temperature arrest of the triiodothyronine-dependent transcription in Rana
      catesbeiana red blood cells.
AB  - We examined possible molecular mechanisms for the low-temperature arrest of T3
      induced Rana catesbeiana metamorphosis. Scatchard plots revealed that the ratios
      of maximum binding capacity/dissociation constant for high-affinity sites of
      tadpole serum proteins for T3 at 20 and 28 C was 3.3-4.6 times less than that at
      4 C, due to the decrease in maximum binding capacity values. Kinetic studies of
      T3 uptake into tadpole red blood cells demonstrated that the ratio of maximum
      uptake rate/Michaelis constant at 23 C was approximately 13 times greater than
      that at 4 C. The process of intracellular transport of T3 into the nucleus was
      not arrested at 4 C. The ratio of T3 incorporated into nuclei to that taken up
      into red blood cells was not significantly different at 4, 20, and 28 C,
      indicating the absence of temperature-sensitive sites in this process. T3 binding
      to the T3 receptors alpha and beta were not temperature sensitive at least at 4
      and 20 C. Transcription of the tr genes, early primary T3 response genes, was
      activated by 10 nM T3 at 20 and 28 C but was barely detected at 4 C. These
      results indicate that the major molecular event causing the low-temperature
      arrest of amphibian metamorphosis occurs after T3 entry into the nucleus but
      before or during the transcriptional activation of the tr genes. Plasma proteins
      binding T3 and the cellular thyroid hormone uptake system on the plasma membrane
      may contribute to the slowing of the incorporation of T3 into nucleus at 4 C by
      decreasing the uptake velocity of T3.

PMID- 15471963
TI  - A system for studying epithelial-stromal interactions reveals distinct inductive
      abilities of stromal cells from benign prostatic hyperplasia and prostate cancer.
AB  - The development of normal and abnormal glandular structures in the prostate is
      controlled at the endocrine and paracrine levels by reciprocal interactions
      between epithelium and stroma. To study these processes, it is useful to have an
      efficient method of tissue acquisition for reproducible isolation of cells from
      defined histologies. Here we assessed the utility of a standardized system for
      acquisition and growth of prostatic cells from different regions of the prostate
      with different pathologies, and we compared the abilities of stromal cells from
      normal peripheral zone, benign prostatic hyperplasia (BPH-S), and cancer to
      induce the growth of a human prostatic epithelial cell line (BPH-1) in vivo.
      Using the tissue recombination method, we showed that grafting stromal cells
      (from any histology) alone or BPH-1 epithelial cells alone produced no visible
      grafts. Recombining stromal cells from normal peripheral zone with BPH-1 cells
      also produced no visible grafts (n = 15). Recombining BPH-S with BPH-1 cells
      generated small, well-organized, and sharply demarcated grafts approximately 3-4
      mm in diameter (n = 9), demonstrating a moderate inductive ability of BPH-S.
      Recombining stromal cells from cancer with BPH-1 cells generated highly
      disorganized grafts that completely surrounded the host kidney and invaded into
      adjacent renal tissue, demonstrating induction of an aggressive phenotype. We
      conclude that acquisition of tissue from toluidine blue dye-stained specimens is
      an efficient method to generate high-quality epithelial and/or stromal cultures.
      Stromal cells derived by this method from areas of BPH and cancer induce
      epithelial cell growth in vivo, which mimics the natural history of these
      diseases.

PMID- 15471965
TI  - Type 2 iodothyronine selenodeiodinase is expressed throughout the mouse skeleton
      and in the MC3T3-E1 mouse osteoblastic cell line during differentiation.
AB  - Thyroid hormone affects multiple aspects of bone metabolism, but little is known
      about thyroid hormone deiodination in bone cells except that cultures of skeletal
      cells and bone organ express types 1 and 2 iodothyronine deiodinases (D1 and D2)
      mRNAs. In the present study, outer ring deiodination (ORD) activity was detected
      in bone extracts of multiple sites of the mouse skeleton, bone marrow, and the
      MC3T3-E1 osteoblastic cell line. In all tissues, ORD was detected using 125I-rT3
      or 125I-T4 as substrates and was found to be 6-n-propylthiouracil insensitive,
      display a Michaelis constant (T4) of approximately 1 nM, increase about 3-fold in
      hypo- and virtually disappear in thyrotoxicosis. Extracts of calvaria had the
      lowest ORD activity, whereas tibial and femoral extracts had roughly three times
      as much. The absence of ORD activity in bone extracts from mice with targeted
      disruption of the Dio2 gene confirms the principal role of D2 in this tissue. In
      the MC3T3-E1 osteoblasts, D2 activity increased in a time-dependent manner after
      plating, and with the content of selenium in the media, reaching a maximum 5-7 d
      later as cells attained more than 90% confluence. In these cells D2 half-life is
      about 30-40 min, which is further accelerated by exposure to substrate and
      stabilized by the proteasome inhibitor, MG132. Treatment with vitamin D
      [1,25(OH)2VD]-induced D2 activity by 2- to 3-fold as early as 24 h, regardless of
      the level of cell confluence, but estradiol, PTH, forskolin, leptin, TNFalpha,
      TGFbeta, and dexamethasone did not affect D2. Given the role of D2 in other cell
      types and processes, it is likely that bone ORD not only plays a role in bone
      development and adult bone T3 homeostasis but also contributes to extrathyroidal
      T3 production and maintenance of serum T3.

PMID- 15471966
TI  - Heparin and activin-binding determinants in follistatin and FSTL3.
AB  - Local regulation of pituitary FSH secretion and many other cellular processes by
      follistatin (FS) can be ascribed to its potent ability to bind and bioneutralize
      activin, in conjunction with binding to cell surface heparan-sulfate
      proteoglycans through a basic heparin-binding sequence (HBS; residues 75-86) in
      the first of the three FS domains. The FS homolog, FSTL3, also binds activin, but
      lacks any HBS and cannot associate with cell surfaces. We have used mutational
      analyses to define the determinants for heparin binding and activin interaction
      in FS and to determine the effects of conferring heparin binding to FSTL3.
      Mutants expressed from 283F cells were tested for cell surface and heparin
      affinity binding, for competitive activin binding and for bioactivity by
      suppression of pituitary cell FSH secretion. Replacement of the HBS or the full
      length FS-domain 1 abolished cell surface binding but enhanced activin binding 4-
      to 8-fold. Surface binding was partially reduced after mutation of either lysine
      pair 75/76 or 81/82 and eliminated after mutation of both pairs. The 75/76
      mutation reduced activin binding and, therefore, pituitary cell bioactivity by 5
      fold. However, insertion of the HBS into FSTL3 did not restore heparin binding or
      pituitary-cell bioactivity. These results show that 1) the residues within the
      HBS are necessary but not sufficient for heparin binding, and 2) the HBS also
      harbors determinants for activin binding. Introduction of the full domain from FS
      conferred heparin binding to FSTL3, but activin binding was abolished. This
      implies an evolutionary safeguard against surface binding by FSTL3, supporting
      other evidence for physiological differences between FS and FSTL3.

PMID- 15471967
TI  - Adenovirus-mediated high expression of resistin causes dyslipidemia in mice.
AB  - The adipocyte-derived hormone resistin has been proposed as a possible link
      between obesity and insulin resistance in murine models. Many recent studies have
      reported physiological roles for resistin in glucose homeostasis, one of which is
      enhancement of glucose production from the liver by up-regulating gluconeogenic
      enzymes such as glucose-6-phosphatase and phosphoenolpyruvate carboxykinase.
      However, its in vivo roles in lipid metabolism still remain to be clarified. In
      this study, we investigated the effects of resistin overexpression on insulin
      action and lipid metabolism in C57BL/6 mice using an adenoviral gene transfer
      technique. Elevated plasma resistin levels in mice treated with the resistin
      adenovirus (AdmRes) were confirmed by Western blotting analysis and RIAs. Fasting
      plasma glucose levels did not differ between AdmRes-treated mice and controls,
      but the basal insulin concentration was significantly elevated in AdmRes-treated
      mice. In AdmRes-treated mice, the glucose-lowering effect of insulin was
      impaired, as evaluated by insulin tolerance tests. Furthermore, total cholesterol
      and triglyceride concentrations were significantly higher, whereas the high
      density lipoprotein cholesterol level was significantly lower. Lipoprotein
      analysis revealed that low-density lipoprotein was markedly increased in AdmRes
      treated mice, compared with controls. In addition, in vivo Triton WR-1339 studies
      showed evidence of enhanced very low-density lipoprotein production in AdmRes
      treated mice. The expressions of genes involved in lipoprotein metabolism, such
      as low-density lipoprotein receptor and apolipoprotein AI in the liver, were
      decreased. These results suggest that resistin overexpression induces
      dyslipidemia in mice, which is commonly seen in the insulin-resistant state,
      partially through enhanced secretion of lipoproteins.

PMID- 15471968
TI  - 17beta-estradiol differentially regulates blood-brain barrier permeability in
      young and aging female rats.
AB  - Because both brain and its vasculature are potent targets of estrogen, age
      related decline in estrogen levels or alterations in estrogen receptors may
      disrupt the integrity of the blood-brain barrier, leading to increased influx of
      toxic products. The present study tested the hypothesis that the blood-brain
      barrier is more permeable in reproductive senescent animals and will respond
      differently to estrogen replacement as compared with young adult females. Young
      adult and reproductive senescent rats were ovariectomized and replaced with an
      estrogen or control pellet. We found a 2- to 4-fold increase in extravasation of
      dye in the olfactory bulb and hippocampus of reproductive senescent females
      compared with young adults. Furthermore, estrogen significantly reduced dye
      extravasation in both olfactory bulb and hippocampus in young adults compared
      with age-matched counterparts that received a control pellet. However, estrogen
      replacement increased dye extravasation in the hippocampus of reproductive
      senescent females compared with age-matched control-pellet replaced animals,
      whereas dye extravasation was unchanged by estrogen in the olfactory bulb of
      senescent females. There were no age- and estrogen-related differences in dye
      accumulation in the pituitary gland, which is a circumventricular organ. These
      results support the hypothesis that the hormonal decline that marks reproductive
      senescence leads to increased permeability of the blood-brain barrier, which is
      further exacerbated by estrogen treatment in specific regions.

PMID- 15471969
TI  - The androgen metabolite, 5alpha-androstane-3beta, 17beta-diol, is a potent
      modulator of estrogen receptor-beta1-mediated gene transcription in neuronal
      cells.
AB  - 5alpha-Androstane-3beta, 17beta-diol (3betaAdiol) is a metabolite of the potent
      androgen, 5alpha-dihydrotestosterone. Recent studies showed that 3betaAdiol binds
      to estrogen receptor (ER)-beta and regulates growth of the prostate gland through
      an estrogen, and not androgen, receptor-mediated pathway. These data raise the
      possibility that 3betaAdiol could regulate important physiological processes in
      other tissues that produce 3betaAdiol, such as the brain. Although it is widely
      accepted that the brain is a target for 5alpha-dihydrotestosterone action, there
      is no evidence that 3betaAdiol has a direct action in neurons. To explore the
      molecular mechanisms by which 3betaAdiol might act to modulate gene transcription
      in neuronal cells, we examined whether 3betaAdiol activates ER-mediated promoter
      activity and whether ER transactivation is facilitated by a classical estrogen
      response element (ERE) or an AP-1 complex. The HT-22 neuronal cell line was
      cotransfected with an expression vector containing ERalpha, ER-beta1, or the
      ERbeta splice variant, ER-beta2 and one of two luciferase-reporter constructs
      containing either a consensus ERE or an AP-1 enhancer site. Cells were treated
      with 100 nM 17beta-estradiol, 100 nM 3betaAdiol, or vehicle for 15 h. We show
      that 3betaAdiol activated ER-beta1-induced transcription mediated by an ERE
      equivalent to that of 17beta-estradiol. By contrast, 3betaAdiol had no effect on
      ERalpha- or ER-beta2-mediated promoter activity. Moreover, ER-beta1 stimulated
      transcription mediated by an ERE and inhibited transcription by an AP-1 site in
      the absence of ligand binding. These data provide evidence for activation of ER
      signaling pathways by an androgen metabolite in neuronal cells.

PMID- 15471970
TI  - Induced angiogenesis with intramedullary direct current: experimental research.
AB  - The purpose of this study was to evaluate angiogenesis after the use of
      intramedullary direct electrical current in rabbit tibia. Thirty-two New Zealand
      rabbits were divided into four groups: group 1, false electrode group; group 2,
      hole group; group 3, control group; and group 4, intramedullary electrical
      stimulation group. One-half of the rabbits in each group were evaluated
      angiographically, pathologically, and scintigraphically on day 7, and the rest
      were evaluated on day 21. Results proved that electrical stimulation was not
      capable of the induction of angiogenesis in the subjects killed on day 7 and day
      21. Furthermore, we found some fibrotic changes secondary to electrical
      stimulation on day 7 (P = 0.04) and day 21 (P = 0.01). However, an increase in
      new capillary vessels occurred in the false electrode group (P = 0.02). We found
      no useful effect of electrical stimulation in our study, a finding that is
      possibly due to our use of a method previously undocumented in the literature. We
      believe that this study can be the new baseline for further studies into the
      stimulation or inhibition of angiogenesis using intramedullary wire with or
      without electrical stimulation.

PMID- 15471971
TI  - Determinants of heart rate variability in obstructive sleep apnea syndrome during
      wakefulness and sleep.
AB  - Heart rate variability (HRV) is mediated by at least three primary mechanisms: 1)
      vagal feedback from pulmonary stretch receptors (PSR), 2) central medullary
      coupling between respiratory and cardiovagal neurons (RCC), and 3) arterial
      baroreflex (ABR)-induced fluctuations. We employed a noninvasive experimental
      protocol in conjunction with a minimal model to determine how these sources of
      HRV are altered in obstructive sleep apnea syndrome (OSAS). Respiration, heart
      rate, and blood pressure were monitored in eight normal subjects and nine
      untreated OSAS patients in relaxed wakefulness and stage 2 and rapid eye movement
      sleep. A computer-controlled ventilator delivered inspiratory pressures that
      varied randomly from breath to breath. Application of the model to the
      corresponding subject responses allowed the delineation of the three components
      of HRV. In all states, RCC gain was lower in OSAS patients than in normal
      subjects (P < 0.04). ABR gain was also reduced in OSAS patients (P < 0.03). RCC
      and ABR gains increased from wakefulness to sleep (P < 0.04). However, there was
      no difference in PSR gain between subject groups or across states. The findings
      of this study suggest that the adverse autonomic effects of OSAS include
      impairment of baroreflex gain and central respiratory-cardiovascular coupling,
      but the component of respiratory sinus arrhythmia that is mediated by lung vagal
      feedback remains intact.

PMID- 15471972
TI  - Daily exercise-induced cardioprotection is associated with changes in calcium
      regulatory proteins in hypertensive rats.
AB  - Epidemiological data document that regular exercise protects against the
      morbidity and mortality associated with ischemic heart disease. Therefore, we
      tested the hypothesis that daily exercise (DE) increases the ventricular
      arrhythmia threshold (VAT) induced by coronary artery occlusion and alters the
      expression of calcium regulatory proteins. The VAT was defined as the time from
      coronary occlusion to sustained ventricular tachycardia resulting in a reduction
      in arterial pressure. To test this hypothesis, we recorded the VAT in conscious
      sedentary normotensive, sedentary hypertensive, and DE hypertensive rats, and we
      associated these thresholds with the protein expression of the L-type calcium
      channel, Na+/Ca2+ exchanger, phospholamban, and sarco(endo)plasmic reticulum
      Ca(2+)-ATPase. Results document a significantly reduced time to ventricular
      arrhythmias (sedentary hypertensive, 3.7 +/- 0.3 min vs. sedentary normotensive,
      4.8 +/- 0.3 min), an increased Na+/Ca2+ exchanger protein expression (47%), and a
      decreased phospholamban protein expression (-34%) in conscious hypertensive rats.
      DE increased the VAT (5.9 +/- 0.2 min), decreased the protein expression of the
      Na+/Ca2+ exchanger, and normalized the protein expression of phospholamban in the
      hypertensive rats. Thus DE may be a primary prevention approach for reducing the
      incidence of arrhythmias by altering calcium regulatory proteins in hypertensive
      rats.

PMID- 15471973
TI  - Embryonic stem cells form an organized, functional cardiac conduction system in
      vitro.
AB  - A functional pacemaking-conduction system is essential for maintaining normal
      cardiac function. However, no reproducible model system exists for studying the
      specialized cardiac pacemaking-conduction system in vitro. Although several
      molecular markers have been shown to delineate components of the cardiac
      conduction system in vivo, the functional characteristics of the cells expressing
      these markers remain unknown. The ability to accurately identify cells that
      function as cardiac pacemaking cells is crucial for being able to study their
      molecular phenotype. In differentiating murine embryonic stem cells, we
      demonstrate the development of an organized cardiac pacemaking-conduction system
      in vitro using the coexpression of the minK-lacZ transgene and the chicken GATA6
      (cGATA6) enhancer. These markers identify clusters of pacemaking "nodes" that are
      functionally coupled with adjacent contracting regions. cGATA6-positive cell
      clusters spontaneously depolarize, emitting calcium signals to surrounding
      contracting regions. Physically separating cGATA6-positive cells from nearby
      contracting regions reduces the rate of spontaneous contraction or abolishes them
      altogether. cGATA6/minK copositive cells isolated from embryoid cells display
      characteristics of specialized pacemaking-conducting cardiac myocytes with regard
      to morphology, action potential waveform, and expression of a hyperpolarization
      activated depolarizing current. Using the cGATA6 enhancer, we have isolated cells
      that exhibit electrophysiological and genetic properties of cardiac pacemaking
      myocytes. Using molecular markers, we have generated a novel model system that
      can be used to study the functional properties of an organized pacemaking
      conducting contracting system in vitro. Moreover, we have used a molecular marker
      to isolate a renewable population of cells that exhibit characteristics of
      cardiac pacemaking myocytes.

PMID- 15471974
TI  - VEGF receptor antagonism blocks arteriogenesis, but only partially inhibits
      angiogenesis, in skeletal muscle of exercise-trained rats.
AB  - Both collateral vessel enlargement (arteriogenesis) and capillary growth
      (angiogenesis) in skeletal muscle occur in response to exercise training.
      Vascular endothelial growth factor (VEGF) is implicated in both processes. Thus
      we examined the effect of a VEGF receptor (VEGF-R) inhibitor (ZD4190,
      AstraZeneca) on collateral-dependent blood flow in vivo and collateral artery
      size ex vivo (indicators of arteriogenesis) and capillary contacts per fiber
      (CCF; an index of angiogenesis) in skeletal muscle of both sedentary and exercise
      trained rats 14 days after bilateral occlusion of the femoral arteries. Total
      daily treadmill run time increased appreciably from approximately 70 to
      approximately 100 min (at 15-20 m/min, twice per day) and produced a large
      (approximately 75%, P < 0.01) increase in calf muscle blood flow and a greater
      size of the collateral artery (wall cross-sectional area). ZD4190, which
      previously has been shown to inhibit the activity of VEGF-R2 and -R1 tyrosine
      kinase in vitro (IC50 = 30 and 700 nM, respectively), completely blocked the
      increase in collateral-dependent blood flow and inhibited collateral vessel
      enlargement. Thus exercise-stimulated collateral arteriogenesis appears to be
      completely dependent on VEGF-R signaling. Interestingly, enhanced mRNA expression
      of the VEGF family ligand placental growth factor (2- to 3.5-fold), VEGF-R1
      (approximately 2-fold), and endothelial nitric oxide synthase (2- to 3.5-fold) in
      an isolated collateral artery implicates these factors as important in
      arteriogenesis. Training of ischemic muscle also induced angiogenesis, as shown
      by an increase (approximately 25%, P < 0.01) in CCF in white gastrocnemius
      muscle. VEGF-R inhibition only partially blocked (P < 0.01) but did not eliminate
      the increase (P < 0.01) in capillarity. Our findings indicate that VEGF-R
      tyrosine kinase activity is essential for collateral arteriogenesis and important
      for the angiogenesis induced in ischemic muscle by exercise training; however,
      other angiogenic stimuli are also important for angiogenesis in flow-limited
      active muscle.

PMID- 15471975
TI  - Reciprocal splanchnic-thoracic blood volume changes during the Valsalva maneuver.
AB  - The Valsalva maneuver is frequently used to test autonomic function. Previous
      work demonstrated that the blood pressure decrease during the Valsalva maneuver
      relates to thoracic hypovolemia, which may preclude pressure recovery during
      phase II, even with normal resting peripheral vasoconstriction. We hypothesized
      that increased regional blood volume, specifically splanchnic hypervolemia,
      accounts for the degree of thoracic hypovolemia during the Valsalva maneuver. We
      studied 17 healthy volunteers aged 15-22 yr. All had normal blood volumes by dye
      dilution. Subjects also had normal vascular resistance while supine as well as
      normal vasoconstrictor responses during 35 degrees upright tilt. We assessed
      changes in estimated splanchnic, pelvic-thigh, and lower leg blood volume, along
      with thoracic blood volume shifts, by impedance plethysmography before and during
      the Valsalva maneuver performed in the supine position. Early increases in
      splanchnic blood volume dominated the regional vascular changes during the
      Valsalva maneuver. The increase in splanchnic blood volume correlated well (r2 =
      0.65, P < 0.00001) with the decrease in thoracic blood volume, there was less
      correlation of the increase in pelvic blood volume (r2 = 0.21, P < 0.03), and
      there was no correlation of the increase in leg blood volume (r2 = 0.001, P =
      0.9). There was no relation of thoracic hypovolemia with blood volume or
      peripheral resistance in supine or upright positions. Thoracic hypovolemia during
      the Valsalva maneuver is closely related to splanchnic hyperemia and weakly
      related to regional changes in blood volume elsewhere. Changes in baseline
      splanchnic vascular properties may account for variability in thoracic blood
      volume changes during the Valsalva maneuver.

PMID- 15471976
TI  - Hemodynamic and biochemical adaptations to vascular smooth muscle overexpression
      of p22phox in mice.
AB  - Protein levels and polymorphisms of p22(phox) have been suggested to modulate
      vascular NAD(P)H oxidase activity and vascular production of reactive oxygen
      species (ROS). We sought to determine whether increasing p22(phox) expression
      would alter vascular ROS production and hemodynamics by targeting p22(phox)
      expression to smooth muscle in transgenic (Tg) mice. Aortas of Tg(p22smc) mice
      had increased p22(phox) and Nox1 protein levels and produced more superoxide and
      H(2)O(2). Surprisingly, endothelium-dependent relaxation and blood pressure in
      Tg(p22smc) mice were normal. Aortas of Tg(p22smc) mice produced twofold more
      nitric oxide (NO) at baseline and sevenfold more NO in response to calcium
      ionophore as detected by electron spin resonance. Western blot analysis revealed
      a twofold increase in endothelial NO synthase (eNOS) protein expression in
      Tg(p22smc) mice. Both eNOS expression and NO production were normalized by
      infusion of the glutathione peroxidase mimetic ebselen or by crossing Tg(p22smc)
      mice with mice overexpressing catalase. We have previously found that NO
      stimulates extracellular superoxide dismutase (ecSOD) expression in vascular
      smooth muscle. In keeping with this, aortic segments from Tg(p22smc) mice
      expressed twofold more ecSOD, and chronic treatment with the NOS inhibitor N(G)
      nitro-L-arginine methyl ester normalized this, suggesting that NO regulates ecSOD
      protein expression in vivo. These data indicate that chronic oxidative stress
      caused by excessive H(2)O(2) production evokes a compensatory response involving
      increased eNOS expression and NO production. NO in turn increases ecSOD protein
      expression and counterbalances increased ROS production leading to the
      maintenance of normal vascular function and hemodynamics.

PMID- 15471977
TI  - Characteristics of the aortic elastic network and related phenotypes in seven
      inbred rat strains.
AB  - Extracellular matrix (ECM) molecules such as elastin and collagen provide
      mechanical support to the vessel wall and are essential for vascular function.
      Evidence that genetic factors influence aortic ECM composition and organization
      was concluded from our previous studies showing that the inbred Brown Norway (BN)
      rat differs significantly from the outbred Long-Evans (LE) and the inbred LOU rat
      with respect to both thoracic aortic elastin content and internal elastic lamina
      (IEL) rupture in the abdominal aorta and iliac arteries. Here, we measured aortic
      elastin and collagen contents as well as factors that may modulate these
      parameters [insulin growth factor (IGF)-I, transforming growth factor (TGF)
      beta(1), and matrix metalloproteinase (MMP)-2] in seven inbred rat strains,
      including BN and LOU. We also investigated whether IEL ruptures occur in strains
      other than BN. We showed that LOU, LE, BN, and Fischer 344 (F344) rats were
      significantly different for aortic elastin content and elastin-to-collagen ratio,
      whereas LE, Lewis, WAG, and Wistar-Furth (WF) were similar for these parameters.
      BN and F344 had the lowest values. BN was the only strain to present numerous IEL
      ruptures, whereas F344, LE, and WF presented a few and the other strains
      presented none. In addition, IGF-I and TGF-beta(1) levels in the plasma and aorta
      differed significantly between strains, suggesting genetic control of their
      production. Because inbred rat strains provide interesting models for
      quantitative trait locus analysis, our results concerning elastin, collagen, IEL
      ruptures, and cytokines may provide a basis for the search for candidate genes
      involved in the control of these phenotypes.

PMID- 15471978
TI  - Frequency-dependent and proarrhythmogenic effects of FK-506 in rat ventricular
      cells.
AB  - FK-506, a widely used immunosuppressant, has caused a few clinical cases with QT
      prolongation and torsades de pointe at high blood concentration. The
      proarrhytmogenic potential of FK-506 was investigated in single rat ventricular
      cells using the whole cell clamp method to record action potentials (APs) and
      ionic currents. Fluorescence measurements of Ca2+ transients were performed with
      indo-1 AM using a multiphotonic microscope. FK-506 (25 micromol/l) hyperpolarized
      the resting membrane potential (RMP; -3 mV) and prolonged APs (AP duration at 90%
      repolarization increased by 21%) at 0.1 Hz. Prolongation was enhanced by
      threefold at 3.3 Hz, and early afterdepolarizations (EADs) occurred in 59% of
      cells. EADs were prevented by stronger intracellular Ca2+ buffering (EGTA: 10 vs.
      0.5 mmol/l in the patch pipette) or replacement of extracellular Na+ by Li+,
      which abolishes Na+/Ca2+ exchange [Na+/Ca2+ exchanger current (INaCa)]. In indo-1
      loaded cells, FK-506 generated doublets of Ca(2+) transients associated with
      increased diastolic Ca2+ in one-half of the cells. FK-506 reversibly decreased
      the L-type Ca2+ current (ICaL) by 25%, although high-frequency-dependent
      facilitation of ICaL persisted, and decreased three distinct K+ currents: delayed
      rectifier K+ current (IK; >80%), transient outward K+ current (<20%), and inward
      rectifier K+ current (IK1; >40%). A shift in the reversal potential of IK1 (-5
      mV) accounted for RMP hyperpolarization. Numerical simulations, reproducing all
      experimental effects of FK-506, and the use of nifedipine showed that frequency
      dependent facilitation of ICaL plays a role in the occurrence of EADs. In
      conclusion, the effects of FK-506 on the cardiac AP are more complex than
      previously reported and include inhibitions of IK1 and ICaL. Alterations in Ca2+
      release and INaCa may contribute to FK-506-induced AP prolongation and EADs in
      addition to the permissive role of ICaL facilitation at high rates of
      stimulation.

PMID- 15471979
TI  - Feedback effects of circulating norepinephrine on sympathetic outflow in healthy
      subjects.
AB  - The amplitude of low-frequency (LF) oscillations of heart rate (HR) usually
      reflects the magnitude of sympathetic activity, but during some conditions, e.g.,
      physical exercise, high sympathetic activity results in a paradoxical decrease of
      LF oscillations of HR. We tested the hypothesis that this phenomenon may result
      from a feedback inhibition of sympathetic outflow caused by circulating
      norepinephrine (NE). A physiological dose of NE (100 ng.kg(-1).min(-1)) was
      infused into eight healthy subjects, and infusion was continued after alpha
      adrenergic blockade [with phentolamine (Phe)]. Muscle sympathetic nervous
      activity (MSNA) from the peroneal nerve, LF (0.04-0.15 Hz) and high frequency
      (HF; 0.15-0.40 Hz) spectral components of HR variability, and systolic blood
      pressure variability were analyzed at baseline, during NE infusion, and during NE
      infusion after Phe administration. The NE infusion increased the mean blood
      pressure and decreased the average HR (P < 0.01 for both). MSNA (10 +/- 2 vs. 2
      +/- 1 bursts/min, P < 0.01), LF oscillations of HR (43 +/- 13 vs. 35 +/- 13
      normalized units, P < 0.05), and systolic blood pressure (3.1 +/- 2.3 vs. 2.0 +/-
      1.1 mmHg2, P < 0.05) decreased significantly during the NE infusion. During the
      NE infusion after PHE, average HR and mean blood pressure returned to baseline
      levels. However, MSNA (4 +/- 2 bursts/min), LF power of HR (33 +/- 9 normalized
      units), and systolic blood pressure variability (1.7 +/- 1.1 mmHg2) remained
      significantly (P < 0.05 for all) below baseline values. Baroreflex gain did not
      change significantly during the interventions. Elevated levels of circulating NE
      cause a feedback inhibition on sympathetic outflow in healthy subjects. These
      inhibitory effects do not seem to be mediated by pressor effects on the
      baroreflex loop but perhaps by a presynaptic autoregulatory feedback mechanism or
      some other mechanism that is not prevented by a nonselective alpha-adrenergic
      blockade.

PMID- 15471980
TI  - Integrin mechanotransduction stimulates caveolin-1 phosphorylation and
      recruitment of Csk to mediate actin reorganization.
AB  - To identify the role of caveolin-1 in integrin mechanotransduction, we exposed
      bovine aortic endothelial cells to 10 dyn/cm2 of laminar shear stress. Caveolin-1
      was acutely and transiently phosphorylated with shear, occurring downstream of
      beta1-integrin activation as the beta1-integrin blocking antibody JB1A was
      inhibitory. In manipulating Src family kinase (SFK) activity with knockdown of
      Csk or type 1 protein phosphatase (PP1) treatment, we observed coordinate
      increase and decrease in shear-induced caveolin-1 phosphorylation, respectively.
      Hence, shear-stimulated caveolin-1 phosphorylation is regulated by SFKs. Shear
      induced recruitment and phosphorylation of caveolin-1 occurred at beta1-integrin
      sites in a beta1-integrin- and SFK-dependent manner. Csk, described to interact
      with pY14-caveolin-1 and integrins, bound to an increased pool of phosphorylated
      caveolin-1 after shear corresponding with elevated Csk at beta1-integrin sites.
      Like caveolin-1, treatment with JB1A and PP1 attenuated shear-induced Csk
      association with beta1-integrins. Csk function was assayed with transfection of a
      caveolin-1 phosphorylation domain peptide. The peptide attenuated shear-induced
      association of Csk at beta1-integrin sites, as well as colocalization of Csk with
      paxillin and phosphorylated caveolin-1. Because integrin and Csk activity
      regulate cytoskeletal reorganization, we evaluated the role of this mechanism in
      shear-induced myosin light chain (MLC) phosphorylation. Knockdown of Csk
      expression was sufficient to reduce MLC diphosphorylation due to shear.
      Disruption of Csk-integrin association by peptide treatment was also inhibitory
      of the MLC diphosphorylation response. Together these data indicate that integrin
      activation with shear stress results in SFK-regulated caveolin-1 phosphorylation
      that, in turn, mediates Csk association at integrin sites, where it plays a role
      in downstream, shear-stimulated MLC diphosphorylation.

PMID- 15471981
TI  - Exogenous NO suppresses flow-induced endothelium-derived NO production because of
      depletion of tetrahydrobiopterin.
AB  - Exogenous nitric oxide (NO) suppresses endothelium-derived NO production. We were
      interested in determining whether this is also the case in flow-induced
      endothelium-derived NO production. If so, then is the mechanism because of
      intracellular depletion of tetrahydrobiopterin [BH4; a cofactor of NO synthase
      (NOS)], which results in superoxide production by uncoupled NOS? Isolated canine
      femoral arteries were perfused with 100 microM S-nitroso-N-acetylpenicillamine
      (SNAP; an NO donor) and/or 64 microM BH4. Perfusion of SNAP suppressed flow
      induced NO production, which was evaluated as a change in the slope of the linear
      relationship between perfusion rate and NO production rate (P < 0.02 vs. control;
      n = 7). Subsequent BH4 perfusion returned the slope to the control level.
      Concomitant perfusion of SNAP and BH4 retained the control-level NO production (n
      = 7). Concomitant perfusion of SNAP and 4,5-dihydroxy-1,3-benzene disulfonic acid
      (Tiron; 1 mM; a membrane-permeable superoxide scavenger) also retained the
      control-level NO production (n = 7), whereas perfusion of Tiron after SNAP could
      not return the NO production to the control level (P < 0.02 vs. control; n = 7).
      We also found a significant decrease in BH4 concentration in the endothelial
      cells after SNAP perfusion. In conclusion, these results indicate that exogenous
      NO suppresses the flow-induced, endothelium-derived NO production by superoxide
      released from uncoupled NOS because of intracellular BH4 depletion.

PMID- 15471982
TI  - Impact of beta-myosin heavy chain isoform expression on cross-bridge cycling
      kinetics.
AB  - Myosin heavy chain (MHC) isoforms alpha and beta have intrinsically different ATP
      hydrolysis activities (ATPase) and therefore cross-bridge cycling rates in
      solution. There is considerable evidence of altered MHC expression in rodent
      cardiac disease models; however, the effect of incremental beta-MHC expression
      over a wide range on the rate of high-strain, isometric cross-bridge cycling is
      yet to be ascertained. We treated male rats with 6-propyl-2-thiouracil (PTU; 0.8
      g/l in drinking water) for short intervals (6, 11, 16, and 21 days) to generate
      cardiac MHC patterns in transition from predominantly alpha-MHC to predominantly
      beta-MHC. Steady-state calcium-dependent tension development and tension
      dependent ATP consumption (tension cost; proportional to cross-bridge cycling)
      were measured in chemically permeabilized (skinned) right ventricular muscles at
      20 degrees C. To assess dynamic cross-bridge cycling kinetics, the rate of force
      redevelopment (ktr) was determined after rapid release-restretch of fully
      activated muscles. MHC isoform content in each experimental muscle was measured
      by SDS-PAGE and densitometry. alpha-MHC content decreased significantly and
      progressively with length of PTU treatment [68 +/- 5%, 58 +/- 4%, 37 +/- 4%, and
      27 +/- 6% for 6, 11, 16, and 21 days, respectively; P < 0.001 (ANOVA)]. Tension
      cost decreased, linearly, with decreased alpha-MHC content [6.7 +/- 0.4, 5.6 +/-
      0.5, 4.0 +/- 0.4, and 3.9 +/- 0.3 ATPase/tension for 6, 11, 16, and 21 days,
      respectively; P < 0.001 (ANOVA)]. Likewise, ktr was significantly and
      progressively depressed with length of PTU treatment [11.1 +/- 0.6, 9.1 +/- 0.5,
      8.2 +/- 0.7, and 6.2 +/- 0.3 s(-1) for 6, 11, 16, and 21 days, respectively; P <
      0.05 (ANOVA)] Thus cross-bridge cycling, under high strain, for alpha-MHC is
      three times higher than for beta-MHC. Furthermore, under isometric conditions,
      alpha-MHC and beta-MHC cross bridges hydrolyze ATP independently of one another.

PMID- 15471983
TI  - Endothelin in the splanchnic vascular bed of DOCA-salt hypertensive rats.
AB  - Vascular capacitance is reduced by endothelin-1 (ET-1) in deoxycorticosterone
      (DOCA)-salt hypertensive rats. This may contribute to hypertension development.
      Because the splanchnic blood vessels (especially veins) are important in
      determining vascular capacitance, we tested the hypothesis that ET-1 levels in
      the splanchnic vasculature are elevated in hypertensive DOCA-salt compared with
      normotensive rats. Tissue ET-1 content was measured by ELISA in aorta, vena cava,
      superior mesenteric artery and vein, and small mesenteric arteries and veins from
      normotensive sham-operated (sham) and 4-wk DOCA-salt rats. We also determined ET
      1 concentration in aortic and portal venous blood (draining the nonhepatic
      splanchnic organs) in anesthetized and conscious sham and DOCA-salt rats before
      and after acute blockade of ETB receptor-mediated plasma clearance of ET-1.
      Results showed a higher ET-1 content in veins than in arteries of similar size.
      However, ET-1 content was similar in vessels from sham and DOCA-salt rats, except
      in aorta and superior mesenteric artery, where ET-1 content was greater in DOCA
      salt rats. ET-1 concentration was significantly higher in portal venous than in
      aortic blood, indicating net nonhepatic splanchnic release (nNHSR) of ET-1.
      However, nNHSR of ET-1 was similar in sham and DOCA-salt rats. Although nNHSR of
      ET-1 increased significantly after ETB receptor blockade in sham rats, it was
      completely unchanged in DOCA-salt rats. These data suggest that, despite the
      absence of ETB receptor-mediated plasma clearance of ET-1, neither the venous
      peptide content nor the net release of ET-1 is increased in the splanchnic
      vasculature of DOCA-salt rats. These results argue against the hypothesis that
      increased venomotor tone in DOCA-salt hypertension is caused by increased ET-1
      concentration around splanchnic venous smooth muscle cells.

PMID- 15471984
TI  - RhoA GTPase regulates L-type Ca2+ currents in cardiac myocytes.
AB  - Regulation of ionic channels plays a pivotal role in controlling cardiac
      function. Here we show that the Rho family of small G proteins regulates L-type
      Ca2+ currents in ventricular cardiomyocytes. Ventricular myocytes isolated from
      transgenic (TG) mice that overexpress the specific GDP dissociation inhibitor Rho
      GDI-alpha exhibited significantly decreased basal L-type Ca2+ current density
      (approximately 40%) compared with myocytes from nontransgenic (NTG) mice. The
      Ca2+ channel agonist BAY K 8644 and the beta-adrenergic agonist isoproterenol
      increased Ca2+ currents in both NTG and TG myocytes to a similar maximal level,
      and no changes in mRNA or protein levels were observed in the Ca2+ channel alpha1
      subunits. These results suggest that the channel activity but not the expression
      level was altered in TG myocytes. In addition, the densities of inward rectifier
      and transient outward K+ currents were unchanged in TG myocytes. The amplitudes
      and rates of basal twitches and Ca2+ transients were also similar between the two
      groups. When the protein was delivered directly into adult ventricular myocytes
      via TAT-mediated protein transduction, Rho GDI-alpha significantly decreased Ca2+
      current density, which supports the idea that the defective Ca2+ channel activity
      in TG myocytes was a primary effect of the transgene. In addition, expression of
      a dominant-negative RhoA but not a dominant-negative Rac-1 or Cdc42 also
      significantly decreased Ca2+ current density, which indicates that inhibition of
      Ca2+ channel activity by overexpression of Rho GDI-alpha is mediated by
      inhibition of RhoA. This study points to the L-type Ca2+ channel activity as a
      novel downstream target of the RhoA signaling pathway.

PMID- 15471985
TI  - Endostatin uncouples NO and Ca2+ response to bradykinin through enhanced O2*-
      production in the intact coronary endothelium.
AB  - The present study tested the hypothesis that endostatin stimulates superoxide
      (O2*-) production through a ceramide-mediating signaling pathway and thereby
      results in an uncoupling of bradykinin (BK)-induced increases in intracellular
      Ca2+ concentration ([Ca2+]i) from nitric oxide (NO) production in coronary
      endothelial cells. With the use of high-speed, wavelength-switching, fluorescence
      imaging techniques, the [Ca2+]i and NO levels were simultaneously monitored in
      the intact endothelium of freshly isolated bovine coronary arteries. Under
      control conditions, BK was found to increase NO production and [Ca2+]i in
      parallel. When the arteries were pretreated with 100 nM human recombinant
      endostatin for 1 h, this BK-induced NO production was reduced by 89%, whereas
      [Ca2+]i was unchanged. With the conversion rate of L-[3H]arginine to L
      [3H]citrulline measured, endostatin had no effect on endothelial NO synthase
      (NOS) activity, but it stimulated ceramide by activation of sphingomyelinase
      (SMase), whereby O2*-. production was enhanced in endothelial cells. O2*-.
      scavenging by tiron and inhibition of NAD(P)H oxidase by apocynin markedly
      reversed the effect of endostatin on the NO response to BK. These results
      indicate that endostatin increases intracellular ceramide levels, which enhances
      O2*-. production through activation of NAD(P)H oxidase. This ceramide-O2*-.
      signaling pathway may contribute importantly to endostatin-induced endothelial
      dysfunction.

PMID- 15471986
TI  - Mechanosensitive cardiac C-fiber response to changes in left ventricular filling,
      coronary perfusion pressure, hemorrhage, and volume expansion in rats.
AB  - Left ventricular (LV) end-diastolic pressure (LVEDP) increase due to volume
      expansion (VExp) enhances mechanosensitive vagal cardiac afferent C-fiber
      activity (CNFA), thus decreasing renal sympathetic nerve activity (RSNA).
      Hypotensive hemorrhage (hHem) attenuates RSNA despite decreased LVEDP. We
      hypothesized that CNFA increases with any change in LVEDP. Coronary perfusion
      pressure (CPP), supposedly affected in both conditions, might also be a stimulus
      of CNFA. VExp and hHem were performed in anesthetized male Sprague-Dawley rats
      while blood pressure, heart rate, and RSNA were measured. Cervical vagotomy
      abolished RSNA response in both reflex responses. Single-unit CNFA was recorded
      while LVEDP was changed. Rapid changes (+/- 4, +/-6, +/-8 mmHg) were obtained by
      graded occlusion of the caval vein and descending aorta. Prolonged changes were
      obtained by VExp and hHem. Furthermore, CNFA was recorded in a modified
      Langendorff heart while CPP was changed (70, 100, 40 mmHg). Rapid LVEDP changes
      increased CNFA [caval vein occlusion: +16 +/- 3 Hz (approximately +602%); aortic
      occlusion: +15 +/- 3 Hz (approximately +553%); 70 units; P < 0.05]. VExp and hHem
      (n = 6) increased CNFA [VExp: +10 +/- 4 Hz (approximately +1,033%); hHem: +10 +/-
      2 Hz (approximately +1,225%); P < 0.05]. An increase in CPP increased CNFA [+2 +/
      1 Hz (approximately +225%); P < 0.05], whereas a decrease in CPP decreased CNFA
      [-0.8 +/- 0.4 Hz (approximately -50%); P < 0.05]. All C fibers recorded
      originated from the LV. CNFA increased with any LVEDP change but changed
      equidirectionally with CPP. Thus neither LVEDP nor CPP fully accounts directly
      for afferent C-fiber and reflex sympathetic responses. The intrinsic afferent
      stimuli and receptive fields accounting for reflex sympathoinhibition still
      remain cryptic.

PMID- 15471987
TI  - Visualization of a functionally enhanced GFP-tagged galanin R2 receptor in PC12
      cells: constitutive and ligand-induced internalization.
AB  - Trafficking of the galanin R2 receptor (GALR2) fused with enhanced GFP (EGFP) was
      studied by using confocal fluorescence microscopy. The fusion protein was
      predominantly localized on the plasma membrane with some intracellular
      fluorescent structures (vesicles), mainly in the perinuclear region. Incubation
      with galanin resulted in a concentration-dependent increase in intracellular Ca2+
      concentration levels, suggesting that the GALR2-EGFP conjugate is functional.
      After blocking endocytosis with methyl-beta-cyclodextrin GALR2-EGFP expression
      was increased on the surface and decreased in the cytoplasm. Blocking endocytic
      recycling with monensin caused an increase of intracellular GALR2-EGFP
      accumulation and a decrease of fluorescence on the plasma membrane. GALR2-EGFP on
      the plasma membrane was internalized within 5-10 min after treatment with galanin
      or AR-M1896, a selective GALR2 agonist, with a dramatic reduction in plasma
      membrane localization and appearance in intracellular vesicles. Neither M35 nor
      M40, two galanin analogues with putative antagonistic action, prevented GALR2
      agonist-induced internalization of GALR2-EGFP, suggesting that they are not
      antagonists at this receptor under the present circumstances. Galanin stimulation
      at low temperature caused GALR2-EGFP aggregation and clustering on the surface
      but no translocation to cytoplasm. After coincubation with galanin the GALR2-EGFP
      was colocalized with internalized Texas red-transferrin, a marker of the clathrin
      endocytic pathway. Hyperosmotic sucrose inhibited internalization of GALR2-EGFP.
      Taken together these findings indicate that GALR2 undergoes constitutive
      endocytosis and recycling and that both ligand-independent and ligand-dependent
      internalization use the clathrin-dependent endocytic recycling pathway.

PMID- 15471988
TI  - Regional crustal thickness and precipitation in young mountain chains.
AB  - Crustal thickness is related to climate through precipitation-induced erosion.
      Along the Andes, the highest mountains and thickest crust (approximately 70 km)
      occur at 25 degrees south, a region of low precipitation. Westerly winds warm
      passing over the Atacama Desert; precipitation is modest in the High Andes and
      eastward over the Altiplano. Severe aridity, hence low erosion rates, helps to
      account for the elevated volcanogenic contractional arc and high, internally
      draining plateau in its rain shadow. Weak erosion along the north-central arc
      provides scant amounts of sediment to the Chile-Peru Trench, starving the
      subduction channel. Subcrustal removal might be expected to reduce the crustal
      thickness, but is not a factor at 25 degrees south. The thickness of the
      gravitationally compensated continental crust cannot reflect underplating and/or
      partial fusion of sediments, but must be caused chiefly by volcanism-plutonism
      and contraction. Contrasting climate typifies the terrain at 45 degrees south
      where moisture-laden westerly winds encounter a cool margin, bringing abundant
      precipitation. The alpine landscape is of lower average elevation compared with
      the north-central Andes and is supported by thinner continental crust
      (approximately 35 km). Intense erosion supplies voluminous clastic debris to the
      offshore trench, and vast quantities are subducted. However, the southern Andean
      crust is only about half as thick as that at 25 degrees south, suggesting that
      erosion, not subcrustal sediment accretion or anatexis, is partly responsible for
      the thickness of the mountain belt. The Himalayas plus Tibetan Plateau, the
      Sierra Nevada plus Colorado Plateau, and the Japanese Islands exhibit analogous
      relationships between crustal thickness and climate.

PMID- 15471989
TI  - Engineering high-level aluminum tolerance in barley with the ALMT1 gene.
AB  - Acidity is a serious limitation to plant production on many of the world's
      agricultural soils. Toxic aluminium (Al) cations solubilized by the acidity
      rapidly inhibit root growth and limit subsequent uptake of water and nutrients.
      Recent work has shown that the ALMT1 gene of wheat (Triticum aestivum) encodes a
      malate transporter that is associated with malate efflux and Al tolerance. We
      generated transgenic barley (Hordeum vulgare) plants expressing ALMT1 and
      assessed their ability to exude malate and withstand Al stress. ALMT1 expression
      in barley conferred an Al-activated efflux of malate with properties similar to
      those of Al-tolerant wheat. The transgenic barley showed a high level of Al
      tolerance when grown in both hydroponic culture and on acid soils. These findings
      provide additional evidence that ALMT1 is a major Al-tolerance gene and
      demonstrate its ability to confer effective tolerance to acid soils through a
      transgenic approach in an important crop species.

PMID- 15471990
TI  - Bacteriolytic therapy can generate a potent immune response against experimental
      tumors.
AB  - When spores of the anaerobic bacterium Clostridium novyi-NT are systemically
      injected into animals, they germinate exclusively within the hypoxic regions of
      cancers. The germinated bacteria destroy adjacent tumor cells but spare a rim of
      well oxygenated tumor cells that subsequently expand. Surprisingly, we found that
      approximately 30% of mice treated with such spores were cured of their cancers
      despite the viable tumor rim initially remaining after spore germination. The
      mechanism underlying this effect was shown to be immune-mediated, because cured
      animals rejected a subsequent challenge of the same tumor. Similar effects were
      observed in rabbits with intrahepatic tumors. It was particularly notable that
      the induced immune response, when combined with the bacteriolytic effects of C.
      novyi-NT, could eradicate large established tumors.

PMID- 15471991
TI  - Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a
      randomized human trial.
AB  - There is increasing evidence that aspirin initiates biosynthesis of novel
      antiinflammatory mediators by means of interactions between endothelial cells and
      leukocytes. These mediators are classified as aspirin-triggered 15-epi-lipoxins.
      Such compounds may account at least in part for aspirin's clinical benefits,
      which are distinct from the well appreciated action of aspirin as a platelet
      inhibitor. Here, we addressed whether aspirin-triggered 15-epilipoxinA4 (ATL)
      formation is aspirin-dependent in humans and its relationship to aspirin's
      antiplatelet activity. We conducted a randomized clinical trial among 128 healthy
      subjects allocated to placebo or to 81-, 325-, or 650-mg daily doses of aspirin
      for 8 weeks. Plasma thromboxane (TX)B2, an indicator of platelet reactivity, and
      ATL were assessed from blood collected at baseline and at 8 weeks. Plasma ATL
      levels significantly increased in the 81-mg aspirin group (0.25 +/- 0.63 ng/ml, P
      = 0.04), with borderline increases in the 325-mg group (0.16 +/- 0.71 ng/ml) and
      no apparent significant changes in the 650-mg group (0.01 +/- 0.75 ng/ml, P =
      0.96). When ATL and TXB2 were compared, levels changed in a statistically
      significant and opposite direction (P < 0.01) for all three aspirin doses. These
      results demonstrated that low-dose aspirin (81 mg daily) initiates production of
      antiinflammatory ATL opposite to the inhibition of TX. Monitoring ATL may
      represent a simple clinical parameter to verify an individual's vascular
      leukocyte antiinflammatory response with low-dose aspirin treatment. These
      results also emphasize the importance of cell-cell interactions in the modulation
      of hemostatic, thrombotic, and inflammatory processes.

PMID- 15471992
TI  - Molecular triangulation: bridging linkage and molecular-network information for
      identifying candidate genes in Alzheimer's disease.
AB  - A major challenge in human genetics is identifying the molecular basis of common
      heritable disorders. In contrast to rare single-gene diseases, multifactorial
      disorders are thought to arise from the combined effect of multiple gene
      variants, such that any single variant may have only a modest effect on disease
      susceptibility. We present a method to identify genes that may harbor a
      significant proportion of the genetic variation that predisposes individuals to a
      given multifactorial disorder. First, we perform an automated literature analysis
      that predicts physical interactions (edges) among candidate disease genes (seed
      nodes, selected on the basis of prior information) and other molecular entities.
      We derive models of molecular networks from this analysis and map the seed nodes
      to them. We then compute the graph-theoretic distance (the minimum number of
      edges that must be traversed) between the seed nodes and all other nodes in the
      network. We assume that nodes that are found in close proximity to multiple seed
      nodes are the best disease-related candidate genes. To evaluate this approach, we
      selected four seed genes, each with a proven role in Alzheimer's disease (AD).
      The method performed well in predicting additional network nodes that match AD
      gene candidates identified manually by an expert. We also show that the method
      prioritizes among the seed nodes themselves, rejecting false-positive seeds that
      are derived from (noisy) whole-genome genetic-linkage scans. We propose that this
      strategy will provide a valuable means to bridge genetic and genomic knowledge in
      the search for genetic determinants of multifactorial disorders.

PMID- 15471993
TI  - Deletion of the synaptic protein interaction site of the N-type (CaV2.2) calcium
      channel inhibits secretion in mouse pheochromocytoma cells.
AB  - Presynaptic N-type Ca2+ channels (CaV2.2, alpha1B) are thought to bind to SNARE
      (SNAP-25 receptor) complex proteins through a synaptic protein interaction
      (synprint) site on the intracellular loop between domains II and III of the
      alpha1B subunit. Whether binding of syntaxin to the N-type Ca2+ channels is
      required for coupling Ca2+ ion influx to rapid exocytosis has been the subject of
      considerable investigation. In this study, we deleted the synprint site from a
      recombinant alpha1B Ca2+ channel subunit and transiently transfected either the
      wild-type alpha1B or the synprint deletion mutant into mouse pheochromocytoma
      (MPC) cell line 9/3L, a cell line that has the machinery required for rapid
      stimulated exocytosis but lacks endogenous voltage-dependent Ca2+ channels.
      Secretion was elicited by activation of exogenously transfected Ca2+ channel
      subunits. The current-voltage relationship was similar for the wild-type and
      mutant alpha1B-containing Ca2+ channels. Although total Ca2+ entry was slightly
      larger for the synprint deletion channel, compared with the wild-type channel,
      when Ca2+ entry was normalized to cell size and limited to cells with similar
      Ca2+ entry (approximately 150 x 10(6) Ca2+ ions/pF cell size), total secretion
      and the rate of secretion, determined by capacitance measurements, were
      significantly reduced in cells expressing the synprint deletion mutant channels,
      compared with wild-type channels. Furthermore, the amount of endocytosis was
      significantly reduced in cells with the alpha1B synprint deletion mutant,
      compared with the wild-type subunit. These results suggest that the synprint site
      is necessary for efficient coupling of Ca2+ influx through alpha1B-containing
      Ca2+ channels to exocytosis.

PMID- 15471994
TI  - Post-antifungal effect of amphotericin B and voriconazole against Aspergillus
      fumigatus analysed by an automated method based on fungal CO2 production:
      dependence on exposure time and drug concentration.
AB  - The post-antifungal effect (PAFE) of amphotericin B and voriconazole, either
      alone or in combination, on Aspergillus fumigatus was studied using an automated
      system based on fungal CO2 production. METHODS: Conidia of A. fumigatus were
      exposed to concentrations of 1-10 x MIC of amphotericin B and 1-40 x MIC of
      voriconazole for 1, 2 and 4 h. After a washing step, exposed and control conidia
      were inoculated into Pedi-BacT culture bottles. CO2 production was automatically
      monitored until the bottles signalled positive. The difference in time span for
      positive signals in drug-exposed and control bottles was used to calculate PAFE.
      RESULTS: There was a linear relationship between inoculum size and time to
      positive signal (r2=0.99). The precision of duplicate analyses was 1.5%. Longer
      exposure times increased the amphotericin B-induced PAFE (P<0.001), whereas
      concentrations above the MIC did not. Voriconazole after 4 h of exposure induced
      a short dose-independent PAFE. The combination with amphotericin B did not
      prolong the PAFE over that caused by amphotericin B alone. CONCLUSIONS: This
      automated method can be used for determination of PAFE. In contrast to Candida
      spp., in which amphotericin B-induced PAFE is mainly related to the area under
      the curve, the effect on A. fumigatus was more dependent on the exposure time.
      This implies that pharmacodynamic data obtained from Candida experiments cannot
      be directly extrapolated to Aspergillus.

PMID- 15471995
TI  - Nucleotide sequence and organization of the multiresistance plasmid pSCFS1 from
      Staphylococcus sciuri.
AB  - OBJECTIVES: The multiresistance plasmid pSCFS1 from Staphylococcus sciuri was
      sequenced completely and analysed with regard to its gene organization and the
      putative role of a novel ABC transporter in antimicrobial resistance. METHODS:
      Plasmid pSCFS1 was transformed into Staphylococcus aureus RN4220, overlapping
      restriction fragments were cloned into Escherichia coli plasmid vectors and
      sequenced. For further analysis of the ABC transporter, a approximately 3 kb
      EcoRV-HpaI fragment was cloned into the staphylococcal plasmid pT181MCS and the
      respective S. aureus RN4220 transformants were subjected to MIC determination.
      RESULTS: A total of 14 ORFs coding for proteins of >100 amino acids were detected
      within the 17 108 bp sequence of pSCFS1. Five of them showed similarity to
      recombination/mobilization genes while another two were similar to plasmid
      replication genes. In addition to the previously described genes cfr for
      chloramphenicol/florfenicol resistance and erm(33) for inducible resistance to
      macrolide-lincosamide-streptogramin B resistance, a Tn554-like spectinomycin
      resistance gene and Tn554-related transposase genes were identified. Moreover, a
      novel ABC transporter was detected and shown to mediate low-level lincosamide
      resistance. CONCLUSION: Plasmid pSCFS1 is composed of various parts which show
      similarity to sequences known to occur on plasmids or transposons of Gram
      positive, but also Gram-negative bacteria. It is likely that pSCFS1 represents
      the result of inter-plasmid recombination events also involving the truncation of
      a Tn554-like transposon.

PMID- 15471996
TI  - Phenotypic and genotypic aminoglycoside resistance in blood culture isolates of
      coagulase-negative staphylococci from a single neonatal intensive care unit, 1989
      2000.
AB  - OBJECTIVES: To investigate the prevalence of aminoglycoside resistance and genes
      encoding aminoglycoside-modifying enzymes (AME) in blood culture isolates of
      coagulase-negative staphylococci (CoNS) from neonates. MATERIALS AND METHODS: A
      total of 180 isolates from 148 patients collected in a single neonatal unit over
      a 12 year period were examined for susceptibility to gentamicin, tobramycin,
      netilmicin, amikacin and arbekacin by Etest and/or disc diffusion. AME genes were
      detected by PCR. RESULTS: The overall non-susceptibility rates to gentamicin,
      tobramycin, netilmicin, amikacin and arbekacin were 66%, 68%, 52%, 38% and 1%,
      respectively. Gentamicin non-susceptibility rates were 4% and 91% in methicillin
      susceptible and -resistant isolates, respectively. aac(6')-Ie-aph(2'')-Ia,
      aph(3')-IIIa and/or ant(4')-Ia were encountered in 125 (69%), 1 (0.5%) and 30
      (16.6%) isolates, respectively. Forty-six (26%) isolates negative for AME genes
      were susceptible to all aminoglycosides. In contrast, 115 (92%), 91 (73%) and 66
      (53%) of aac(6')-Ie-aph(2'')-Ia positive isolates were non-susceptible to
      gentamicin, netilmicin and amikacin, respectively. Only one isolate showed
      arbekacin resistance. However, aac(6')-Ie-aph(2'')-Ia positive isolates and
      isolates with gentamicin MIC > or =128 mg/L displayed a significant reduction in
      arbekacin inhibition zones. CONCLUSIONS: A high prevalence of aminoglycoside
      resistance was detected and associated with methicillin resistance. Discrepancies
      between phenotypic and genetic detection of aminoglycoside resistance were
      discerned. Gentamicin was the preferred substrate for phenotypic detection of
      aac(6')-Ie-aph(2'')-Ia. Arbekacin showed favourable antibacterial activity even
      in aac(6')-Ie-aph(2'')-Ia-positive isolates. We suggest including arbekacin in
      future clinical trials of empirical treatment of late onset neonatal sepsis.

PMID- 15471997
TI  - Evaluation of the MicroScan ESBL plus confirmation panel for detection of
      extended-spectrum beta-lactamases in clinical isolates of oxyimino-cephalosporin
      resistant Gram-negative bacteria.
AB  - OBJECTIVE: We aimed to assess the performance of the MicroScan ESBL plus
      confirmation panel using a series of 87 oxyimino-cephalosporin-resistant Gram
      negative bacilli of various species. METHODS: Organisms tested included 57
      extended-spectrum beta-lactamase (ESBL) strains comprising Enterobacter aerogenes
      (3), Enterobacter cloacae (10), Escherichia coli (11), Klebsiella pneumoniae
      (26), Klebsiella oxytoca (3) and Proteus mirabilis (4). Also included were 30
      strains resistant to oxyimino cephalosporins but lacking ESBLs, which were
      characterized with other resistance mechanisms, such as inherent clavulanate
      susceptibility in Acinetobacter spp. (4), hyperproduction of AmpC enzyme in
      Citrobacter freundii (2), E. aerogenes (3), E. cloacae (3), E. coli (4), Hafnia
      alvei (1) and Morganella morganii (1), production of plasmid-mediated AmpC beta
      lactamase in K. pneumoniae (3) and E. coli (3) or hyperproduction of K1 enzyme in
      K. oxytoca (6). RESULTS: The MicroScan MIC-based clavulanate synergy correctly
      classified 50 of 57 ESBL strains as ESBL-positive and 23 of 30 non-ESBL strains
      as ESBL-negative (yielding a sensitivity of 88% and a specificity of 76.7%,
      respectively). False negatives among ESBL producers were highest with
      Enterobacter spp. due to masking interactions between ESBL and AmpC beta
      lactamases. False-positive classifications occurred in two Acinetobacter spp.,
      one E. coli producing plasmid-mediated AmpC beta-lactamase and two K. oxytoca
      hyperproducing their chromosomal K1 beta-lactamase. CONCLUSION: The MicroScan
      clavulanate synergy test proved to be a valuable tool for ESBL confirmation.
      However, this test has limitations in detecting ESBLs in Enterobacter spp. and in
      discriminating ESBL-related resistance from the K1 enzyme and from inherent
      clavulanate susceptibility in Acinetobacter spp.

PMID- 15471998
TI  - Antibiotic resistance of faecal Escherichia coli from healthy volunteers from
      eight developing countries.
AB  - OBJECTIVES: To determine the prevalence of antibiotic-resistant faecal
      Escherichia coli from adult volunteers from urban (U) areas in Kenya, Mexico,
      Peru and the Philippines, and non-urban (NU) locations in Curacao, Mexico,
      Venezuela, Ghana, Zimbabwe and the Philippines. METHODS: Faecal samples of adult
      volunteers (n=1290) were analysed in one laboratory for the presence of
      antimicrobial-resistant E. coli using Eosin Methylene Blue agar plates
      containing, respectively, ampicillin, oxytetracycline, cefazolin, ciprofloxacin,
      gentamicin, chloramphenicol and trimethoprim at breakpoint concentrations.
      RESULTS: The mean age of the volunteers was approximately 35 years; most of them
      were female. Ciprofloxacin resistance was in the range 1%-63%: the highest
      percentages were found in the urban populations of Asia and South America. In
      Peru and the Philippines (U and NU), the prevalence of gentamicin resistance was
      >20%. Cefazolin resistance was the highest in the urban Philippines (25%). Higher
      prevalences for ampicillin, oxytetracycline and trimethoprim were found for urban
      areas compared with non-urban ones of Asia, Africa and South America,
      respectively (P<0.05). CONCLUSIONS: In the populations studied, antibiotic
      resistance in faecal E. coli from adult volunteers was emerging for cefazolin,
      gentamicin and ciprofloxacin and was high for the older drugs ampicillin,
      oxytetracycline, trimethoprim and chloramphenicol.

PMID- 15471999
TI  - Antibiotics in media for isolation of Campylobacter spp. do not enhance
      resistance.

PMID- 15472000
TI  - Identification of a chromosome-borne class C beta-lactamase from Erwinia
      rhapontici.
AB  - OBJECTIVES: To characterize the beta-lactamase gene content of Erwinia
      rhapontici. METHODS: The beta-lactamase gene was cloned, sequenced and expressed
      in Escherichia coli. RESULTS: The cloned gene conferred a resistance pattern of
      an Ambler class C beta-lactamase in E. coli. The AmpC-type enzyme had a pI value
      of 8.6 and shared 62% amino acid sequence identity with that of Escherichia
      fergusonii. The ampC gene was associated with a regulatory ampR gene and beta
      lactamase production was inducible. CONCLUSIONS: This work provides further
      evidence of the molecular heterogeneity of beta-lactamases in Erwinia spp. and
      that plant-pathogenic enterobacterial species may constitute a reservoir of
      antibiotic resistance genes.

PMID- 15472001
TI  - In vitro activity of ertapenem against selected respiratory pathogens.
AB  - OBJECTIVES: The in vitro activity of ertapenem was evaluated in comparison to 21
      selected agents against a large collection of recently isolated respiratory tract
      pathogens including: 180 Streptococcus pneumoniae, 100 Streptococcus pyogenes, 70
      Haemophilus influenzae, 70 Moraxella catarrhalis, 100 methicillin-susceptible
      Staphylococcus aureus and 30 Klebsiella pneumoniae. Additional in vitro tests
      (time-kill curves with ertapenem alone and in combination with four other agents)
      for S. pneumoniae were carried out. METHODS: MIC determinations and time-kill
      curves were carried out following the procedures suggested by the NCCLS. RESULTS:
      According to NCCLS susceptibility breakpoints, ertapenem was comparable to the
      most potent compounds tested for all pathogens studied. Ertapenem was 100% active
      against penicillin-susceptible and -intermediate S. pneumoniae and against 60% of
      penicillin-resistant strains. Time-kill tests at 4x MIC confirmed a pronounced
      bactericidal potency of ertapenem against these organisms. Interactions of
      ertapenem with several other agents against pneumococci resulted in clear
      synergic interactions (98.4%). Indifference was extremely rare and antagonism was
      not observed. All S. pyogenes strains tested were inhibited by ertapenem,
      irrespective of their macrolide resistance phenotypes. Ertapenem was also fully
      active against H. influenzae (100% susceptible) and M. catarrhalis (MIC90 0.015
      0.03 mg/L) even when capable of synthesizing beta-lactamases. Methicillin
      susceptible S. aureus and K. pneumoniae, including extended-spectrum beta
      lactamase-producing strains, were 100% susceptible to ertapenem. CONCLUSIONS: Our
      results indicate that ertapenem has a suitable spectrum of activity against
      organisms encountered in community-acquired bacterial respiratory tract
      infections.

PMID- 15472002
TI  - Detection of CTX-M-1 and TEM-52 beta-lactamases in Escherichia coli strains from
      healthy pets in Portugal.

PMID- 15472003
TI  - Impact of plasma protein binding on antimicrobial activity using time-killing
      curves.
AB  - OBJECTIVES: Plasma protein binding (PPB) is known to impair the antimicrobial
      activity of beta-lactams, but its impact on the activity of other classes of
      antimicrobials such as fluoroquinolones is controversial. This study was
      undertaken to investigate the effect of PPB on bacterial killing by selected
      antibiotics and moxifloxacin, which served as a model compound for the class of
      fluoroquinolones. METHODS: Bacterial time-killing curves were employed in the
      absence and presence of physiological albumin concentrations (40 g/L).
      Moxifloxacin, ampicillin and oxacillin were investigated. Fosfomycin, a non
      protein bound antibiotic was used for comparison. Simulations were carried out by
      employing concentrations of antibiotics of one-fourth of the minimal inhibitory
      concentration (MIC), equal to the MIC and four-fold the MIC of one select
      bacterial strain (Staphylococcus aureus ATCC 29213). To correlate bacterial
      killing to the extent of PPB, bacterial time-killing curves were plotted using
      the calculated free and the total drug concentration. RESULTS: Bacterial killing
      by fosfomycin was not affected by the addition of albumin. The antimicrobial
      activity of oxacillin and ampicillin was reduced in the presence of albumin as
      expected by the calculation of the free fraction of these antibiotics. Adding
      albumin to moxifloxacin resulted in a significant decrease in bacterial killing
      of more than 1 log10 cfu/mL after a period of 8 h when the moxifloxacin
      concentration was equal to the respective MIC. CONCLUSIONS: Our data confirm the
      view that albumin substantially impairs the antimicrobial activity of antibiotics
      including moxifloxacin, a member of the class of fluoroquinolones.

PMID- 15472004
TI  - In vitro bactericidal activity of antimicrobial agents against enterohaemorrhagic
      Escherichia coli.
AB  - OBJECTIVES: In vitro bactericidal activity of four antimicrobial agents was
      determined against nine strains of enterohaemorrhagic Escherichia coli. METHODS:
      Pulsed-field gel electrophoresis was carried out with the Bio-Rad Gene Path
      system. Each antimicrobial agent was added to logarithmic phase of
      enterohaemorrhagic E. coli (four strains of E. coli O157:H7, two of E. coli O26,
      two of E. coli O111, and one of E. coli O165) in broth to obtain a concentration
      of 10 or 50 mg/L, and viable cells were counted after 1, 2, 6 and 24 h. RESULTS:
      All nine strains were confirmed to differ in their DNA pattern by pulsed-field
      gel electrophoresis. Norfloxacin at concentrations of 10 and 50 mg/L had
      bactericidal effects on all nine strains of enterohaemorrhagic E. coli. However,
      cefoperazone, kanamycin and fosfomycin had no bactericidal effects on some
      strains. In particular, after addition of 10 mg/L fosfomycin or kanamycin, four
      of the nine strains showed proliferation. CONCLUSIONS: Norfloxacin had marked
      bactericidal effects on enterohaemorrhagic E. coli. This information could be of
      value in planning randomized clinical trials of antimicrobial agents as treatment
      for enterohaemorrhagic E. coli infection.

PMID- 15472005
TI  - Outbreak of multi-resistant Klebsiella oxytoca involving strains with extended
      spectrum beta-lactamases and strains with extended-spectrum activity of the
      chromosomal beta-lactamase.
AB  - OBJECTIVES: This study was conducted to analyse broad-spectrum cephalosporin
      resistant Klebsiella oxytoca strains. METHODS: The 57 isolates studied were
      recovered from clinical specimens (n=23) or from rectal swabs (n=34) during a 26
      month period. Antibiotic susceptibility patterns were determined using standard
      agar diffusion and dilution methods including the synergy test between extended
      spectrum cephalosporins and clavulanic acid. ERIC-2 PCR and pulsed-field gel
      electrophoresis (PFGE) methods were used to study the clonal relatedness of the
      strains. Plasmid-mediated and chromosomal beta-lactamases were characterized by
      mating and specific bla gene amplification and sequencing. RESULTS: Four
      different antibiotic resistance patterns were identified whereas ERIC-2 PCR and
      PFGE revealed six main profiles. Extended-spectrum beta-lactamases (ESBLs) were
      found in 32 strains: TEM-7 (n=26), TEM-129 (n=1), TEM-3 (n=4), SHV-2 (n=1). The
      new TEM-type beta-lactamase, TEM-129, differed from TEM-7 by one mutation (Glu
      104-->Lys). All TEM-7 or TEM-129 producers were genetically related. Twenty-five
      other strains with identical ERIC-2 PCR and PFGE profiles harboured a bla(OXY-2)
      gene different from the reference gene: 24 strains displayed one substitution
      (Ala-237-->Ser) in the KTG motif and one strain, highly resistant to ceftazidime,
      showed an additional substitution (Pro-167-->Ser). CONCLUSIONS: The study
      demonstrated that the majority of strains (n=52) harbouring the OXY-2-type beta
      lactamase corresponded to two clones. The first clone (n=27) corresponded to ESBL
      producing strains. The second clone (n=25) displayed extended-spectrum activity
      of the chromosomal beta-lactamase.

PMID- 15472006
TI  - Positive virological outcome after lopinavir/ritonavir salvage therapy in
      protease inhibitor-experienced HIV-1-infected children: a prospective cohort
      study.
AB  - BACKGROUND: Lopinavir/ritonavir has demonstrated antiviral activity in the HIV
      infected patient. OBJECTIVE: To analyse virological response to
      lopinavir/ritonavir therapy in previously protease inhibitor (PI)-experienced HIV
      1-infected children. MATERIALS AND METHODS: Sixty-seven HIV-1-children on
      lopinavir/ritonavir were studied in a multicentre prospective cohort
      observational study. The outcome variables were undetectable viral load (uVL; VL
      < or =400 copies/mL) and virological failure after uVL with a rebound of VL >400
      copies/mL. VL and genotype of HIV-1-isolates were measured using standard assays.
      RESULTS: 83.5% of children had a 1 log10 VL decrease including 65.6% who reached
      uVL. Children with >2 changes of antiretroviral therapy (ART) or >5 drugs needed
      a median time of 3-4 months higher than children with < or =2 changes of ART or <
      or =5 drugs previous to lopinavir/ritonavir, to reach those values, and the
      relative proportions (RP) were 2.2 (P =0.038) and 1.9 (P=0.050), respectively.
      Children with CD4+>15% (P=0.122), VL < or =30,000 (P < 0.001) copies/mL, and age
      >12 years (P=0.096) achieved an earlier control of VL during the follow-up. The
      children with virological failure or rebound of VL had higher baseline VL and
      lower CD4+ T-lymphocytes/mm3 and had taken a greater number of drugs previous to
      lopinavir/ritonavir. HIV-children with a new nucleoside reverse transcriptase
      inhibitor (NRTI), or protease inhibitor (PI) or PI plus non-nucleoside reverse
      transcriptase inhibitors (NNRTI) in the current regimen had a better virological
      response than children without these new drugs. Also, children with <6 protease
      mutations had an RP of 2.31 of achieving uVL. CONCLUSIONS: Highly active
      antiretroviral therapy (HAART) including lopinavir/ritonavir induces beneficial
      effects in terms of virological outcome responses, and it is an effective option
      for salvage therapy in PI-experienced HIV-1-infected children.

PMID- 15472007
TI  - Antioxidant defense responses to sleep loss and sleep recovery.
AB  - Sleep deprivation in humans is widely believed to impair health, and sleep is
      thought to have powerful restorative properties. The specific physical and
      biochemical factors and processes mediating these outcomes, however, are poorly
      elucidated. Sleep deprivation in the animal model produces a condition that
      eventually becomes highly lethal, lacks specific localization, and is reversible
      with sleep, implying mediation by a biochemical abnormality. Metabolic and
      immunological consequences of sleep deprivation point to a high potential for
      antioxidant imbalance. The objective, therefore, was to study glutathione content
      in the liver, heart, and lung, because glutathione is considered a major free
      radical scavenger that reflects the degree to which a tissue has been oxidatively
      challenged. We also investigated major enzymatic antioxidants, including catalase
      and glutathione peroxidase, as well as indexes of glutathione recycling. Catalase
      activity and glutathione content, which normally are tightly regulated, were both
      decreased in liver by 23-36% by 5 and 10 days of sleep deprivation. Such levels
      are associated with impaired health in other animal models of oxidative stress
      associated disease. The decreases were accompanied by markers of generalized cell
      injury and absence of responses by the other enzymatic antioxidants under study.
      Enzymatic activities in the heart indicated an increased rate of oxidative
      pentose phosphate pathway activity during sleep deprivation. Recovery sleep
      normalized antioxidant content in liver and enhanced enzymatic antioxidant
      activities in both the liver and the heart. The present results link
      uncompensated oxidative stress to health effects induced by sleep deprivation and
      provide evidence that restoration of antioxidant balance is a property of
      recovery sleep.

PMID- 15472008
TI  - Role of paraventricular nucleus in the cardiogenic sympathetic reflex in rats.
AB  - Myocardial ischemia stimulates cardiac spinal afferents to initiate a
      sympathoexcitatory reflex. However, the pathways responsible for generation of
      increased sympathetic outflow in this reflex are not fully known. In this study,
      we determined the role of the paraventricular nucleus (PVN) in the cardiogenic
      sympathetic reflex. Renal sympathetic nerve activity (RSNA) and blood pressure
      were recorded in anesthetized rats during epicardial application of 10 microg/ml
      bradykinin. Bilateral microinjection of muscimol (0.5 nmol), a GABA(A) receptor
      agonist, was performed to inhibit the PVN. In 10 vehicle-injected rats,
      epicardial bradykinin significantly increased RSNA 178.4 +/- 48.5% from baseline,
      and mean arterial pressure from 76.9 +/- 2.0 to 102.3 +/- 3.3 mmHg.
      Microinjection of muscimol into the PVN significantly reduced the basal blood
      pressure and RSNA (n = 12). After muscimol injection, the bradykinin-induced
      increases in RSNA (111.6 +/- 35.9% from baseline) and mean arterial pressure
      (61.2 +/- 1.3 to 74.5 +/- 2.7 mmHg) were significantly reduced compared with
      control responses. The response remained attenuated even when the basal blood
      pressure was restored to the control. In a separate group of rats (n = 9),
      bilateral microinjection of the ionotropic glutamate antagonist kynurenic acid
      (4.82 or 48.2 nmol in 50 nl) had no significant effect on the RSNA and blood
      pressure responses to bradykinin compared with controls. These results suggest
      that the tonic PVN activity is important for the full manifestation of the
      cardiogenic sympathoexcitatory response. However, ionotropic glutamate receptors
      in the PVN are not directly involved in this reflex response.

PMID- 15472009
TI  - Plantar vibration improves leg fluid flow in perimenopausal women.
AB  - Recent studies have indicated that plantar-based vibration may be an effective
      approach for the prevention and treatment of osteoporosis. We addressed the
      hypothesis of whether the plantar vibration operated by way of the skeletal
      muscle pump, resulting in enhanced blood and fluid flow to the lower body. We
      combined plantar stimulation with upright tilt table testing in 18 women aged 46
      63 yr. We used strain-gauge plethysmography to measure calf blood flow, venous
      capacitance, and the microvascular filtration relation, as well as impedance
      plethysmography to examine changes in leg, splanchnic, and thoracic blood flow
      while supine at a 35 degrees upright tilt. A vibrating platform was placed on the
      footboard of a tilt table, and measurements were made at 0, 15, and 45 Hz with an
      amplitude of 0.2 g point to point, presented in random order. Impedance-measured
      supine blood flows were significantly (P = 0.05) increased in the calf (30%),
      pelvic (26%), and thoracic regions (20%) by plantar vibration at 45 Hz. Moreover,
      the 25-35% decreases in calf and pelvic blood flows associated with upright tilt
      were reversed by plantar vibration, and the decrease in thoracic blood flow was
      significantly attenuated. Strain-gauge measurements showed an attenuation of
      upright calf blood flow. In addition, the microvascular filtration relation was
      shifted with vibration, producing a pronounced increase in the threshold for
      edema, P(i), due to enhanced lymphatic flow. Supine values for P(i) increased
      from 24 +/- 2 mmHg at 0 Hz to 27 +/- 3 mmHg at 15 Hz, and finally to 31 +/- 2
      mmHg at 45 Hz (P < 0.01). Upright values for P(i) increased from 25 +/- 3 mmHg at
      0 Hz, to 28 +/- 4 mmHg at 15 Hz, and finally to 35 +/- 4 mmHg at 45 Hz. The
      results suggest that plantar vibration serves to significantly enhance peripheral
      and systemic blood flow, peripheral lymphatic flow, and venous drainage, which
      may account for the apparent ability of such stimuli to influence bone mass.

PMID- 15472010
TI  - Chronic maternal feed restriction impairs growth but increases adiposity of the
      fetal guinea pig.
AB  - Small size at birth has been associated with an increased risk of central obesity
      and reduced lean body mass in adult life. This study investigated the time of
      onset of prenatally induced obesity, which occurs after maternal feed
      restriction, in the guinea pig, a species that, like the human, develops
      substantial adipose tissue stores before birth. We examined the effect of
      maternal feed restriction [70% ad libitum intake from 4 wk before to
      midpregnancy, then 90% until day 60 gestation (term approximately 69 days)] on
      fetal growth and body composition in the guinea pig. Maternal feed restriction
      reduced fetal (-39%) and placental (-30%) weight at 60 days gestation and reduced
      liver, biceps muscle, spleen, and thymus weights, relative to fetal weight, while
      relative weights of brain, lungs, and interscapular and retroperitoneal fat pads
      were increased. In the interscapular depot, maternal feed restriction decreased
      the volume density of multilocular fat and increased that of unilocular fat,
      resulting in an increased relative weight of interscapular unilocular fat.
      Maternal feed restriction did not alter the relative weight of perirenal fat or
      the volume density of adipocyte populations within the depot but increased
      unilocular lipid locule size. Maternal feed restriction in the guinea pig is
      associated with decreased weight of major organs, including liver and skeletal
      muscle, but increased adiposity of the fetus, with relative sparing of unilocular
      adipose tissue. If this early-onset obesity persists, it may contribute to the
      metabolic and cardiovascular dysfunction that these offspring of feed-restricted
      mothers develop as adults.

PMID- 15472011
TI  - Cathepsin B inactivation attenuates hepatocyte apoptosis and liver damage in
      steatotic livers after cold ischemia-warm reperfusion injury.
AB  - Hepatic steatosis predisposes the liver to cold ischemia-warm reperfusion (CI/WR)
      injury by unclear mechanisms. Because hepatic steatosis has recently been
      associated with a lysosomal pathway of apoptosis, our aim was to determine
      whether this cell-death pathway contributes to CI/WR injury of steatotic livers.
      Wild-type and cathepsin B-knockout (Ctsb(-/-)) mice were fed the
      methionine/choline-deficient (MCD) diet for 2 wk to induce hepatic steatosis.
      Mouse livers were stored in the University of Wisconsin solution for 24 h at 4
      degrees C and reperfused for 1 h at 37 degrees C in vitro. Immunofluorescence
      analysis of the lysosomal enzymes cathepsin B and D showed a punctated
      intracellular pattern consistent with lysosomal localization in wild-type mice
      fed a standard diet after CI/WR injury. In contrast, cathepsin B and D
      fluorescence became diffuse in livers from wild-type mice fed MCD diet after
      CI/WR, indicating that lysosomal permeabilization had occurred. Hepatocyte
      apoptosis was rare in both normal and steatotic livers in the absence of CI/WR
      injury but increased in wild-type mice fed an MCD diet and subjected to CI/WR
      injury. In contrast, hepatocyte apoptosis and liver damage were reduced in Ctsb(
      /-) and cathepsin B inhibitor-treated mice fed the MCD diet following CI/WR
      injury. In conclusion, these findings support a prominent role for the lysosomal
      pathway of apoptosis in steatotic livers following CI/WR injury.

PMID- 15472012
TI  - Annexin-1 is an endogenous gastroprotective factor against indomethacin-induced
      damage.
AB  - Adherence of neutrophils to the vascular endothelium is an early and critical
      event in the pathogenesis of gastric injury induced by NSAIDs. Pretreatment with
      glucocorticoids has been shown to prevent NSAID-induced neutrophil adherence and,
      in turn, to protect the stomach from injury. Some of the anti-inflammatory
      effects of glucocorticoids, including inhibition of neutrophil adherence, are
      mediated via the release of annexin-1. In this study, we assessed the
      contribution of annexin-1 to the protective actions of a glucocorticoid
      (dexamethasone) against indomethacin-induced gastric damage. Dexamethasone
      pretreatment markedly reduced the extent of indomethacin-induced gastric damage
      in rats. Immunoneutralization of annexin-1 resulted in a reversal of the
      gastroprotective actions of dexamethasone. Similarly, pretreatment with either of
      two antagonists of the formyl peptide receptor family, to which annexin-1 binds,
      reversed the gastroprotective effects of dexamethasone. The inhibitory effects of
      dexamethasone on indomethacin-induced leukocyte adherence in the mesenteric
      microcirculation were abolished by pretreatment with an antibody directed against
      annexin-1 or with an antagonist of the formyl peptide receptors. These results
      demonstrate that annexin-1 mediates the gastroprotective effects of a
      glucocorticoid against NSAID-induced damage. We propose that in some
      circumstances, annexin-1 plays an important role as an endogenous mediator of
      mucosal defense.

PMID- 15472013
TI  - Proteins of interstitial cells of Cajal and intestinal smooth muscle, colocalized
      with caveolin-1.
AB  - The murine jejunum and lower esophageal sphincter (LES) were examined to
      determine the locations of various signaling molecules and their colocalization
      with caveolin-1 and one another. Caveolin-1 was present in punctate sites of the
      plasma membranes (PM) of all smooth muscles and diffusely in all classes of
      interstitial cells of Cajal (ICC; identified by c-kit immunoreactivity), ICC
      myenteric plexus (MP), ICC-deep muscular plexus (DMP), ICC-serosa (ICC-S), and
      ICC-intramuscularis (IM). In general, all ICC also contained the L-type Ca(2+) (L
      Ca(2+)) channel, the PM Ca(2+) pump, and the Na(+)/Ca(2+) exchanger-1 localized
      with caveolin-1. ICC in various sites also contained Ca(2+)-sequestering
      molecules such as calreticulin and calsequestrin. Calreticulin was present also
      in smooth muscle, frequently in the cytosol, whereas calsequestrin was present in
      skeletal muscle of the esophagus. Gap junction proteins connexin-43 and -40 were
      present in circular muscle of jejunum but not in longitudinal muscle or in LES.
      In some cases, these proteins were associated with ICC-DMP. The large-conductance
      Ca(2+)-activated K(+) channel was present in smooth muscle and skeletal muscle of
      esophagus and some ICC but was not colocalized with caveolin-1. These findings
      suggest that all ICC have several Ca(2+)-handling and -sequestering molecules,
      although the functions of only the L-Ca(2+) channel are currently known. They
      also suggest that gap junction proteins are located at sites where
      ultrastructural gap junctions are know to exist in circular muscle of intestine
      but not in other smooth muscles. These findings also point to the need to
      evaluate the function of Ca(2+) sequestration in ICC.

PMID- 15472014
TI  - Neuromuscular control of aerodynamic forces and moments in the blowfly,
      Calliphora vicina.
AB  - Flies are among the most agile of flying insects, a capacity that ultimately
      results from their nervous system's control over steering muscles and aerodynamic
      forces during flight. In order to investigate the relationships among
      neuromuscular control, musculo-skeletal mechanics and flight forces, we captured
      high-speed, three-dimensional wing kinematics of the blowfly, Calliphora vicina,
      while simultaneously recording electromyogram signals from prominent steering
      muscles during visually induced turns. We used the quantified kinematics to
      calculate the translational and rotational components of aerodynamic forces and
      moments using a theoretical quasi-steady model of force generation, confirmed
      using a dynamically scaled mechanical model of a Calliphora wing. We identified
      three independently controlled features of the wingbeat trajectory--downstroke
      deviation, dorsal amplitude and mode. Modulation of each of these kinematic
      features corresponded to both activity in a distinct steering muscle group and a
      distinct manipulation of the aerodynamic force vector. This functional
      specificity resulted from the independent control of downstroke and upstroke
      forces rather than the independent control of separate aerodynamic mechanisms.
      The predicted contributions of each kinematic feature to body lift, thrust, roll,
      yaw and pitch are discussed.

PMID- 15472015
TI  - Voluntary running in deer mice: speed, distance, energy costs and temperature
      effects.
AB  - The energetics of terrestrial locomotion are of considerable interest to
      ecologists and physiologists, but nearly all of our current knowledge comes from
      animals undergoing forced exercise. To explore patterns of energy use and
      behavior during voluntary exercise, we developed methods allowing nearly
      continuous measurements of metabolic rates in freely behaving small mammals, with
      high temporal resolution over periods of several days. We used this approach to
      examine relationships between ambient temperature (Ta), locomotor behavior and
      energy costs in the deer mouse, a small mammal that routinely encounters a large
      range of temperatures in its natural habitat. We tested for individual
      consistency in running behavior and metabolic traits, and determined how
      locomotor costs vary with speed and Ta. Because of the importance of
      thermoregulatory costs in small mammals, we checked for substitution of exercise
      heat for thermostatic heat production at Ta below the thermal neutral zone and
      determined the fraction of the daily energy budget comprising exercise costs.
      Locomotor behavior was highly variable among individuals but had high
      repeatability, at least over short intervals. We found few temperature-related
      changes in speed or distance run, but Ta strongly affected energy costs. Partial
      substitution of exercise heat for thermogenic heat occurred at low Ta. This
      reduced energy expenditure during low-temperature running by 23-37%, but running
      costs comprised a fairly minor fraction of the energy budget, so the daily energy
      savings via substitution were much smaller. Deer mice did not adjust running
      speed to maximize metabolic economy, as they seldom used the high speeds that
      provide the lowest cost of transport. The highest voluntary speeds (4-5 km h(-1))
      were almost always below the predicted maximal aerobic speed, and were much less
      than the species' maximal sprint speed. Maximum voluntarily attained rates of
      oxygen consumption (VO2) were highest at low Ta, but rarely approached maximal
      VO2 during forced treadmill exercise. Mean respiratory exchange ratios coincident
      with maximal voluntary VO2 increased slightly as Ta declined, but were always
      below 1.0 (another indication that metabolic rate was less than the aerobic
      maximum). Individuals with high running performance (cumulative distance and
      running time) had high resting metabolism, which suggests a cost of having high
      capacity or propensity for activity.

PMID- 15472016
TI  - No hemoglobin but NO: the icefish (Chionodraco hamatus) heart as a paradigm.
AB  - The role of nitric oxide (NO) in cardio-vascular homeostasis is now known to
      include allosteric redox modulation of cell respiration. An interesting animal
      for the study of this wide-ranging influence of NO is the cold-adapted Antarctic
      icefish Chionodraco hamatus, which is characterised by evolutionary loss of
      hemoglobin and multiple cardio-circulatory and subcellular compensations for
      efficient oxygen delivery. Using an isolated, perfused working heart preparation
      of C. hamatus, we show that both endogenous (L-arginine) and exogenous (SIN-1 in
      presence of SOD) NO-donors as well as the guanylate cyclase (GC) donor 8Br-cGMP
      elicit positive inotropism, while both nitric oxide synthase (NOS) and sGC
      inhibitors, i.e. L-NIO and ODQ, respectively, induce significant negative
      inotropic effects. These results therefore demonstrate that under basal working
      conditions the icefish heart is under the tonic influence of a NO-cGMP-mediated
      positive inotropism. We also show that the working heart, which has intracardiac
      NOS (shown by NADPH-diaphorase activity and immunolocalization), can produce and
      release NO, as measured by nitrite appearance in the cardiac effluent. These
      results indicate the presence of a functional NOS system in the icefish heart,
      possibly serving a paracrine/autocrine regulatory role.

PMID- 15472017
TI  - Acclimatization to 4100 m does not change capillary density or mRNA expression of
      potential angiogenesis regulatory factors in human skeletal muscle.
AB  - Increased skeletal muscle capillary density would be a logical adaptive mechanism
      to chronic hypoxic exposure. However, animal studies have yielded conflicting
      results, and human studies are sparse. Neoformation of capillaries is dependent
      on endothelial growth factors such as vascular endothelial growth factor (VEGF),
      a known target gene for hypoxia inducible factor 1 (HIF-1). We hypothesised that
      prolonged exposure to high altitude increases muscle capillary density and that
      this can be explained by an enhanced HIF-1alpha expression inducing an increase
      in VEGF expression. We measured mRNA levels and capillary density in muscle
      biopsies from vastus lateralis obtained in sea level residents (SLR; N=8) before
      and after 2 and 8 weeks of exposure to 4100 m altitude and in Bolivian Aymara
      high-altitude natives exposed to approximately 4100 m altitude (HAN; N=7). The
      expression of HIF-1alpha or VEGF mRNA was not changed with prolonged hypoxic
      exposure in SLR, and both genes were similarly expressed in SLR and HAN. In SLR,
      whole body mass, mean muscle fibre area and capillary to muscle fibre ratio
      remained unchanged during acclimatization. The capillary to fibre ratio was lower
      in HAN than in SLR (2.4+/-0.1 vs 3.6+/-0.2; P<0.05). In conclusion, human muscle
      VEGF mRNA expression and capillary density are not significantly increased by 8
      weeks of exposure to high altitude and are not increased in Aymara high-altitude
      natives compared with sea level residents.

PMID- 15472018
TI  - Morphology predicts suction feeding performance in centrarchid fishes.
AB  - Suction feeding fish differ in their capacity to generate subambient pressure
      while feeding, and these differences appear to relate to morphological variation.
      We developed a morphological model of force transmission in the fish head and
      parameterized it with measurements from individual fish. The model was applied to
      45 individuals from five species of centrarchid fishes: Lepomis macrochirus,
      Lepomis punctatus, Lepomis microlophus, Micropterus salmoides and Pomoxis
      nigromaculatus. Measurements of epaxial cross-sectional area, epaxial moment arm,
      buccal area and buccal area moment arm were combined to estimate pressure
      generation capacity for individual fish. This estimation was correlated with
      pressure measured in fish feeding on elusive prey to test the model's ability to
      predict pressure generation from morphology. The model explained differences in
      pressure generation found among individuals (P<0.001, r2=0.71) and produced a
      realistic estimate of normalized muscle stress during suction feeding (68.5+/-6.7
      kPa). Fish with smaller mouths, larger epaxial cross-sectional area and longer
      epaxial moments, such as L. macrochirus (bluegill sunfish), generated lower
      pressures than fish with larger mouths, smaller cross-sectional area and shorter
      moments, such as M. salmoides (largemouth bass). These results reveal a direct
      trade-off between morphological requirements of feeding on larger prey (larger
      mouth size relative to body depth) and the ability to generate subambient
      pressure while suction feeding on elusive prey.

PMID- 15472019
TI  - Motor units are recruited in a task-dependent fashion during locomotion.
AB  - Muscle fibres have a range of contractile properties from fast to slow.
      Traditional understanding of muscle fibre recruitment suggests that the slower
      fibres within a mixed muscle are used for all contractions including those at
      rapid speeds. However, mechanical arguments predict that some locomotor tasks are
      best performed by solely the faster fibres. Motor recruitment patterns can be
      indicated by the spectral properties of the myoelectric signals. High- and low
      frequency myoelectric spectra that have similar spectral power indicate the
      activity of faster and slower motor units, respectively. In this study, the
      myoelectric signals in humans were measured from nine muscles of the leg during
      walking and running at 1.5, 3 and 4.5 m s(-1). The myoelectric spectra for 20
      points in each stride were calculated using wavelet techniques, and the spectral
      properties quantified using principal component analysis. Bursts of muscle
      activity were characterized by hysteresis in the myoelectric frequencies, with
      different frequencies occurring at different times, indicating time-varying
      shifts in the motor recruitment patterns. This hysteresis occurred at all
      locomotor speeds tested. It is likely that the different types of motor unit are
      recruited in a task-dependent fashion during locomotion.

PMID- 15472020
TI  - Developmental changes in cardiorespiratory patterns associated with terrestrial
      apnoeas in harbour seal pups.
AB  - During the nursing period seals undergo several physiological and behavioural
      changes. A key component of development is increased cardiorespiratory control,
      fundamental for breath-holding and thus diving. This study focused on the
      ontogenetic changes in cardiac responses to respiration in quietly resting, pre
      weaned harbour seal pups (Phoca vitulina). During periods of quiet rest,
      breathing became episodic, eupnoea interspersed with periods of apnoea. Little
      change was observed in respiration (approximately 35 breaths min(-1)) and
      eupnoeic heart rate (approximately 160 beats min(-1)) throughout the nursing
      period. However, apnoea duration increased (from approximately 20 to 40 s), while
      apnoeic heart rate decreased with age (from approximately 150 to 90 beats min(
      1)). The observed decline in apnoeic heart rate resulted from an increase in
      cardiorespiratory control as pups approached weaning, evident by the ability to
      maintain a lower heart rate more consistently. Similar changes in
      cardiorespiratory patterns have been reported for elephant and Weddell seals. Due
      to the early onset of independent foraging, however, the rate of
      cardiorespiratory control development was more rapid in harbour seals. Our
      findings suggest that by 1 month of age, harbour seal pups possess the
      cardiorespiratory control necessary to sustain long-duration apnoeas, fundamental
      for proficient diving and successful foraging upon weaning.

PMID- 15472021
TI  - Motor output characterizing thanatosis in the cricket Gryllus bimaculatus.
AB  - The cricket Gryllus bimaculatus displays a sudden rigid immobility (thanatosis)
      when voluntary leg movements are forcibly restrained. The tibial joints in all
      legs are stiffly immobilized for several minutes. The flexed-leg posture typical
      of thanatosis is maintained by the flexor tibiae muscle. To characterize
      thanatosis at the motor output level, the mechanical and physiological properties
      of the metathoracic tibia muscle were investigated. The accessory flexor muscle,
      especially well-developed in the cricket, acts to stably maintain the tibial
      flexion driven by the main flexor muscle. Extracellular recordings from the
      flexor muscle of tethered crickets revealed that activity of intermediate- and
      fast-excitatory units was almost completely suppressed, while slow-excitatory
      units persisted in firing tonically during thanatosis. The firing rate of slow
      excitatory units progressively increased as the tibia flexed, but remained less
      than the firing rate seen in the quiescent state. Common inhibitory motor
      neurones that fire sporadically in the quiescent state were suppressed during
      thanatosis, especially in the beginning, and showed a large excitation
      immediately after arousal. These findings suggest that the entire motor neuronal
      pool is held under active suppression during thanatosis, and that flexor muscle
      rigidity is maintained by a weak discharge of the slow exciters together with
      suppression of the inhibitors.

PMID- 15472022
TI  - Heart rate and energetics of free-ranging king penguins (Aptenodytes
      patagonicus).
AB  - The main objective of this study was to determine heart rate (fh) and the
      energetic costs of specific behaviours of king penguins while ashore and while
      foraging at sea during their breeding period. In particular, an estimate was made
      of the energetic cost of diving in order to determine the proportion of dives
      that may exceed the calculated aerobic dive limit (cADL; estimated usable O2
      stores/estimated rate of oxygen consumption during diving). An implanted data
      logger enabled fh and diving behaviour to be monitored from 10 free-ranging king
      penguins during their breeding period. Using previously determined calibration
      equations, it was possible to estimate rate of oxygen consumption (VO2) when the
      birds were ashore and during various phases of their foraging trips. Diving
      behaviour showed a clear diurnal pattern, with a mixture of deep (>40 m), long
      (>3 min) and shallow (<40 m), short (<3 min) dives from dawn to dusk and shallow,
      short dives at night. Heart rate during dive bouts and dive cycles (dive + post
      dive interval) was 42% greater than that when the birds were ashore. During
      diving, fh was similar to the 'ashore' value (87+/-4 beats min(-1)), but it did
      decline to 76% of the value recorded from king penguins resting in water. During
      the first hour after a diving bout, fh was significantly higher than the average
      value during diving (101+/-4 beats min(-1)) and for the remainder of the dive
      bout. Rates of oxygen consumption estimated from these (and other) values of fh
      indicate that when at sea, metabolic rate (MR) was 83% greater than that when the
      birds were ashore [3.15 W kg(-1) (-0.71, +0.93), where the values in parentheses
      are the computed standard errors of the estimate], while during diving bouts and
      dive cycles, it was 73% greater than the 'ashore' value. Although estimated MR
      during the total period between dive bouts was not significantly different from
      that during dive bouts [5.44 W kg(-1) (-0.30, +0.32)], MR during the first hour
      following a dive bout was 52% greater than that during a diving bout. It is
      suggested that this large increase following diving (foraging) activity is, at
      least in part, the result of rewarming the body, which occurs at the end of a
      diving bout. From the measured behaviour and estimated values of VO2, it was
      evident that approximately 35% of the dives were in excess of the cADL. Even if
      VO2 during diving was assumed to be the same as when the birds were resting on
      water, approximately 20% of dives would exceed the cADL. As VO2 during diving is,
      in fact, that estimated for a complete dive cycle, it is quite feasible that VO2
      during diving itself is less than that measured for birds resting in water. It is
      suggested that the regional hypothermia that has been recorded in this species
      during diving bouts may be at least a contributing factor to such hypometabolism.

PMID- 15472023
TI  - A set of female pheromones affects reproduction before, during and after mating
      in Drosophila.
AB  - Sex pheromones are chemical signals used for mate attraction and discrimination
      in many invertebrate species. These compounds are often complex mixtures with
      different components having different effects. We tested live Drosophila
      melanogaster mutant female flies genetically depleted for unsaturated cuticular
      hydrocarbons, which were then perfumed with these substances to measure their
      influence on various aspects of reproduction. Female pheromones of the control Cs
      strain enhanced female attractivity, copulation duration and tended to decrease
      the number of female progeny of mutant females mated with Cs males, but no dose
      dependent effect was found. Cs and variant males showed different response to Cs
      female pheromone, suggesting a strain-specific coadaptation of female and male
      characters. The fact that female pheromones induced reciprocal effects on the
      frequency of the genes contributed by females and males suggests that these
      substances regulate coevolutionary processes between the sexes.

PMID- 15472024
TI  - Characterization of the voltage-activated currents in cultured atrial myocytes
      isolated from the heart of the common oyster Crassostrea gigas.
AB  - Using the macro-patch clamp technique, we show that cardiac myocytes isolated
      from the heart of the oyster Crassostrea gigas possess several types of voltage
      activated ionic currents. (1) A classical non-inactivating potassium current of
      the IK type that is inhibited by tetraethyl ammonium and shows an outward
      rectification and a slow activation. (2) A potassium current of the IA type that
      shows rapid activation and inactivation, and is blocked by 4-amino pyridine or
      preliminary depolarisation. (3) A potassium calcium-dependent current that is
      inhibited by charybdotoxin, activated by strong depolarisations and shows a large
      conductance. (4) A calcium inward current of the L-type that is inhibited by
      verapamil, cobalt and high concentrations of cadmium. This current is identified
      in most cells, but a T-type calcium current and classical fast sodium current are
      only identified in few cells, and only after a strong hyperpolarizing pulse. This
      suggests that these channels are normally inactivated in cultured cells and are
      not involved in the spontaneous activity of these cells. When they exist, the
      fast sodium channel is blocked by tetrodotoxin. The L-type calcium conductance is
      increased by serotonin. The identification in cultured oyster atrial cells of
      classical ionic currents, which are observed in most vertebrate species but only
      in a few species of molluscs, demonstrates that these cells are an interesting
      model. Moreover the viability and the electrophysiological properties of these
      cells are not significantly modified by freezing and thawing, thus increasing
      their usefulness in various bioassays.

PMID- 15472025
TI  - Hydrodynamics of surface swimming in leopard frogs (Rana pipiens).
AB  - The kinematics of swimming frogs have been studied extensively in the past and,
      based on these results, hypotheses regarding the hydrodynamics of frog swimming
      can be generated. To test these hypotheses we used digital particle image
      velocimetry (DPIV) to quantify the flow structure of the wake produced by the
      feet during the propulsion phase of the kick of surface swimming frogs (Rana
      pipiens). These frogs use two different gaits, asynchronous and synchronous
      kicking, and the magnitude of the thrust produced by the feet differs between
      asynchronous (34+/-5.4 mN foot(-1)) and synchronous kicking (71+/-13.3 mN foot(
      1)), as does maximum swimming speed, with higher swimming speed and forces
      produced during the synchronous kicks. Previous studies have suggested that an
      interaction between the feet, resulting in a single posteriorly directed fluid
      jet, as the feet come together at the end of synchronous kicks, may augment force
      production. Our results show, however, that each foot produces its own distinct
      vortex ring, in both asynchronous and synchronous kicking of the feet. There is
      no evidence of a central jet being produced even during powerful synchronous
      kicks (maximum thrust calculated was 264 mN foot(-1)). An alternative mechanism
      of force production could be the lift-based paddling recently suggested for delta
      shaped feet of swimming birds. However, the orientation of the vortex rings
      generated by the feet is almost perpendicular to the swimming direction for both
      gaits and there is only a slight asynchrony of the shedding of the distal (start)
      and proximal (stop) vortex rings, which is different from what would be expected
      by a dominantly lift-based mechanism. Thus, our results do not support lift as a
      major mechanism contributing to thrust. Instead, our data support the hypothesis
      that propulsion is based on drag and acceleration reaction forces where the
      thrust is generated by separated, but attached, vortex rings on the suction side
      of the feet, resulting in vortices that are shed behind the frogs during both
      asynchronous and synchronous kicking.

PMID- 15472026
TI  - Comparison of the cost of short flights in a nectarivorous and a non
      nectarivorous bird.
AB  - Although most birds are accustomed to making short flights, particularly during
      foraging, the flight patterns during these short periods of activity differ
      between species. Nectarivorous birds, in particular, often spend time hovering,
      while non-nectarivorous birds do not. The cost of short flights is likely
      therefore to differ between nectarivorous and non-nectarivorous birds because of
      the different energetic contributions of different flight types to the behaviour.
      The 13C-labelled bicarbonate technique was used to measure the energy cost of
      short flights in the nectarivorous Palestine sunbird Nectarinia osea (mean mass
      6.17+/-0.16 g, N=8) and the non-nectarivorous starling Sturnus vulgaris (mean
      mass 70.11+/-1.11 g, N=9). The technique was initially calibrated in five
      individuals for each species at temperatures ranging from 1 to 35 degrees C, by
      comparing the isotope elimination rate to the metabolic rate measured
      simultaneously by indirect calorimetry. The cost for short intermittent flight
      was then measured by encouraging birds to fly between two perches at either end
      of a narrow corridor (perch distance for sunbirds, 6 m; for starlings, 5 m), and
      measuring the amount of isotope eliminated during the flight. The isotope
      elimination rate was interpolated onto the calibration equation to predict flight
      cost, as a direct calibration could not be performed during flight. Mean energy
      expenditure during flight was 1.64+/-0.32 W in sunbirds, while in starlings the
      flight costs averaged 20.6+/-0.78 W. Energy cost of flight relative to basal
      metabolic rate was substantially greater in the starling than the sunbird.
      Phylogenetic analysis of different modes of flight in these and additional
      species suggests that differences in flight behaviour may cause these elevated
      costs in slow flying non-nectarivores such as starlings, compared to birds that
      are more prone to short intermittent flights like the sunbirds.

PMID- 15472027
TI  - The energy cost of loaded flight is substantially lower than expected due to
      alterations in flight kinematics.
AB  - The effect of experimentally increased wing loading on the energy cost of flight
      was examined in cockatiels Nyphicus hollandicus. Five individuals were flown for
      periods of approximately 2 min, while carrying additional payload mass amounting
      to between 5 and 20% of unloaded body mass. The energy cost of flight was
      measured using the 13C-labelled bicarbonate technique, which was also calibrated
      in a separate experiment on resting birds, by comparing the elimination rate of
      13C in breath with a simultaneous measurement of oxygen consumption by indirect
      calorimetry. It was not possible to perform a similar calibration during flight
      when energy costs were higher, so we extrapolated the relationship from the
      resting calibration to predict flight cost. Flight cost in the pre-manipulated
      individuals averaged 16.7+/-1.8 W. Flight cost in the pre-manipulated birds was
      significantly related to the interaction between downstroke duration and flight
      speed. There was no significant increase in flight cost with increases in payload
      mass. The birds responded to payload masses between 5 and 15% of their unloaded
      body mass by decreasing flight speed relative to unloaded birds, while
      maintaining wing beat frequency (Fb). At a payload mass equivalent to 20% of body
      mass, however, the birds flew at higher speeds than unloaded controls, and had a
      significantly higher Fb, generated by a reduction in both the upstroke and
      downstroke durations. Wing amplitude was unaffected by the increase in loading.
      Using the measured flight parameters, the effect of loading was not significantly
      different than predicted using aerodynamic models.

PMID- 15472028
TI  - The energetic cost of variations in wing span and wing asymmetry in the zebra
      finch Taeniopygia guttata.
AB  - Asymmetry is a difference in the sizes of bilaterally paired structures. Wing
      asymmetry may have an effect on the kinematics of flight, with knock-on effects
      for the energetic cost of flying. In this study the 13C-labelled bicarbonate
      technique was used to measure the energy expended during the flight of zebra
      finches Taeniopygia guttata, prior to and after experimental manipulation to
      generate asymmetry and a change in wing span by trimming the primary feathers. In
      addition, simultaneous high-speed video footage enabled differences in flight
      kinematics such as flight speed, wing amplitude, up- and downstroke duration and
      wing beat frequency to be examined. In 10 individuals, the primary feathers on
      the right wing were trimmed first, by 0.5 cm, and then by an additional 0.5 cm in
      six of these individuals. In a separate 'control' group (N=7), approximately 0.25
      cm was trimmed off the primary feathers of both wings, to produce the same
      reduction in wing span as 0.5 cm trimmed from one wing, while maintaining
      symmetry. When birds were manipulated to become asymmetric they maintained flight
      speed. They also increased the left wing amplitude and decreased the right up-
      and downstroke durations to counteract the changes in wing shape, which meant
      that they had an increase in wing beat frequency. When the wing area was reduced
      while maintaining symmetry, birds flew with slower flight speed. In this case
      wing amplitude did not change and wing upstroke slightly decreased, causing an
      increased wing beat frequency. The mean flight cost in the pre-manipulated birds
      was 1.90+/-0.1 W. There was a slight increase in flight cost with both of the
      asymmetry manipulations (0.5 cm, increase of 0.04 W; 1.0 cm, increase of 0.12 W),
      neither of which reached statistical significance. There was, however, a
      significantly increased flight cost when the wing span was reduced without
      causing asymmetry (increase of 0.45 W; paired t-test T=2.3, P=0.03).

PMID- 15472029
TI  - The effects of head and tail stimulation on the withdrawal startle response of
      the rope fish (Erpetoichthys calabaricus).
AB  - While most actinopterygian fishes perform C-start or S-start behaviors as their
      primary startle responses, many elongate species instead use a withdrawal
      movement. Studies of withdrawal have focused on the response to head-directed or
      nonspecific stimuli. During withdrawal, the animal moves its head back from the
      stimulus, often resulting in several tight bends in the body. In contrast to C
      start or S-start behaviors, withdrawal to a head stimulus generally does not
      involve a subsequent propulsive stage of movement. We examined intraspecific
      diversity in withdrawal behavior and muscle activity patterns of the rope fish,
      Erpetoichthys calabaricus, in response to stimulation of the head and the tail.
      In addition, we describe the anatomy of the Mauthner cells and their axon caps,
      structures that are generally absent in species with a withdrawal startle. We
      recorded high-speed video (250 Hz) and electromyograms (EMGs) from 12 electrodes
      in the axial muscle during the behavioral response. We used Bodian silver
      staining techniques to visualize Mauthner cell and axon cap morphology. We found
      that E. calabaricus responds with a withdrawal to both head and tail stimulation.
      Tail stimulation elicits a stronger kinematic and muscle activity response than
      head stimulation. While withdrawal movement generally constitutes the entire
      response to head stimuli, withdrawal was followed by propulsive movements when
      the tail was stimulated, suggesting that withdrawal can both act alone and serve
      as the first stage of a propulsive startle. Unexpectedly, bilaterality of muscle
      activity was variable for responses to both head and tail stimuli. In addition,
      we were surprised to find that E. calabaricus has a distinct axon cap associated
      with its Mauthner cell. These data suggest that the withdrawal response is a more
      diverse functional system than has previously been believed.

PMID- 15472030
TI  - Blue integumentary structural colours in dragonflies (Odonata) are not produced
      by incoherent Tyndall scattering.
AB  - For nearly 80 years, the non-iridescent, blue, integumentary structural colours
      of dragonflies and damselflies (Odonata) have been attributed to incoherent
      Tyndall or Rayleigh scattering. We investigated the production of the
      integumentary structural colours of a damselfly--the familiar bluet, Enallagma
      civile (Coenagrionidae)--and a dragonfly--the common green darner, Anax junius
      (Aeshnidae)--using fibre optic spectrophotometry and transmission electron
      microscopy (TEM). The reflectance spectra of both species showed discrete
      reflectance peaks of approximately 30% reflectance at 475 and 460 nm,
      respectively. These structural colours are produced by light scattering from
      closely packed arrays of spheres in the endoplasmic reticulum of box-shaped
      epidermal pigment cells underlying the cuticle. The observed reflectance spectra
      do not conform to the inverse fourth power relationship predicted for
      Tyndall/Rayleigh scattering. Two-dimensional (2-D) Fourier analysis of the TEM
      images of the colour-producing arrays reveals ring-shaped distributions of
      Fourier power at intermediate spatial frequencies, documenting a quasiordered
      nanostructure. The nanostructured Fourier power spectra falsify the assumption of
      spatial independence of scatterers that is required for incoherent scattering.
      Radial averages of the Fourier power spectrum indicate that the spheres are
      substantially nanostructured at the appropriate spatial scale to produce visible
      colours by coherent scattering. However, the spatial periodicity of the arrays is
      apparently too large to produce the observed colour by coherent scattering. The
      nanospheres could have expanded substantially (approximately 50%) during
      preparation for TEM. Alternatively, coherent light scattering could be occurring
      both from the surfaces and from structures at the centre of the spheres. These
      arrays of colour-producing spheres within pigment cells have convergently evolved
      at least 11-14 times independently within the Odonata. Structural colouration
      from arrays in living cells has also fostered the convergent evolution of
      temperature-dependent colour change in numerous odonate lineages.

PMID- 15472031
TI  - Analysis of subforms of free prostate-specific antigen in serum by two
      dimensional gel electrophoresis: potential to improve diagnosis of prostate
      cancer.
AB  - BACKGROUND: The aim of this study was to develop a method to separate and
      quantify subforms of free prostate-specific antigen (fPSA) in serum by two
      dimensional electrophoresis and to assess the diagnostic accuracy of these
      subforms for prostate cancer (PCa) diagnosis in comparison with total PSA (tPSA)
      and the ratio of fPSA to tPSA (%fPSA). METHODS: Sera from 50 patients with and
      without PCa, respectively, were studied. PSA was isolated by immunoadsorption on
      streptavidin-coated magnetic beads with biotinylated anti-PSA antibodies and
      separated by two-dimensional electrophoresis. After semidry blotting, the
      intensities of the fPSA spots were quantified by chemiluminescence using an
      imager analyzer. RESULTS: The method detected subforms to a concentration of 0.1
      mug/L fPSA with an imprecision (CV) <16%. We detected 15 immunoreactive fPSA
      spots of different intensities. Spots F2 and F3 were present in all samples. F2
      was lower in samples from non-PCa patients (median, 23%) than in samples from PCa
      patients (49%), whereas F3 behaved inversely (non-PCa, 73%; PCa, 45%). Ratios of
      F2 to F3 and F2/F3 to %fPSA, respectively, showed improved diagnostic accuracy
      compared with tPSA and %fPSA. Better differentiation by F2/F3 or by F2/F3 to
      %fPSA was particularly evident in patients with %fPSA values >15%. There were no
      associations between the PCa grading scale and fPSA subforms. CONCLUSIONS: fPSA
      subforms separated by two-dimensional electrophoresis may improve both
      sensitivity and specificity in prostate cancer diagnostics compared with tPSA and
      %fPSA. The development of a practicable assay based on the immunologic properties
      of these different fPSA subforms seems to be promising.

PMID- 15472032
TI  - Performance characteristics of six third-generation assays for thyroid
      stimulating hormone.
AB  - BACKGROUND: Thyroid-stimulating hormone (TSH) is used to detect primary hypo- and
      hyperthyroidism. Current guidelines for TSH assays recommend a functional
      sensitivity of < or =0.02 mIU/L. The protocol for determining the functional
      sensitivity of TSH assays specifies analyses of serum samples with two reagent
      lots over a 6- to 8-week period. METHODS: We determined the functional
      sensitivities of the Access 2, ADVIA Centaur, ARCHITECT i2000, E170, IMMULITE
      2000, and Vitros ECi automated methods, using seven serum pools and two reagent
      lots for each method. RESULTS: The observed functional sensitivities were as
      follows: Access 2, <0.020 mIU/L; ADVIA Centaur, 0.039 mIU/L; ARCHITECT i2000,
      <0.005 mIU/L; Elecsys E170, 0.011 mIU/L; IMMULITE 2000, 0.014 mIU/L; Vitros ECi,
      0.004 mIU/L. However, there were large differences between some method means for
      the seven serum pools. For the pool with the lowest TSH concentration, mean
      results were as follows: Access 2, 0.0203 mIU/L; ADVIA Centaur, 0.0085 mIU/L;
      ARCHITECT i2000, 0.0049 mIU/L; E170, 0.0098 mIU/L; IMMULITE 2000, 0.0077 mIU/L;
      Vitros ECi, 0.0014 mIU/L. Method-comparison studies using samples with TSH
      concentrations >0.2 mIU/L also showed method differences. The ARCHITECT i2000
      method was the most precise at low TSH concentrations. CONCLUSIONS: TSH methods
      do not provide comparable results for serum pools with TSH concentrations <0.2
      mIU/L or for patient results across the analytic measurement range. Further
      investigation into the cause of these differences and additional harmonization
      efforts are required.

PMID- 15472033
TI  - Simultaneous and sensitive measurement of anabasine, nicotine, and nicotine
      metabolites in human urine by liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Determination of nicotine metabolism/pharmacokinetics provides a
      useful tool for estimating uptake of nicotine and tobacco-related toxicants, for
      understanding the pharmacologic effects of nicotine and nicotine addiction, and
      for optimizing nicotine dependency treatment. METHODS: We developed a sensitive
      method for analysis of nicotine and five major nicotine metabolites, including
      cotinine, trans-3'-hydroxycotinine, nicotine-N'-oxide, cotinine-N-oxide, and
      nornicotine, in human urine by liquid chromatography coupled with a TSQ Quantum
      triple quadrupole tandem mass spectrometer (LC/MS/MS). Urine samples to which
      deuterium-labeled internal standards had been added were extracted with a simple
      solid-phase extraction procedure. Anabasine, a minor tobacco alkaloid, was also
      included. RESULTS: The quantification limits of the method were 0.1-0.2 microg/L,
      except for nicotine (1 microg/L). Cotinine-N-oxide, trans-3'-hydroxycotinine,
      nicotine, and anabasine in urine were almost completely recovered by the solid
      phase extraction, whereas the mean extraction recoveries of nicotine-N'-oxide,
      cotinine, and nornicotine were 51.4%, 78.6%, and 78.8%, respectively. This
      procedure provided a linearity of three to four orders of magnitude for the
      target analytes: 0.2-400 microg/L for nicotine-N'-oxide, cotinine-N-oxide, and
      anabasine; 0.2-4000 microg/L for cotinine, nornicotine, and trans-3'
      hydroxycotinine; and 1.0-4000 microg/L for nicotine. The overall interday method
      imprecision and recovery were 2.5-18% and 92-109%, respectively. CONCLUSIONS:
      This sensitive LC/MS/MS procedure can be used to determine nicotine metabolism
      profiles of smokers, people during nicotine replacement therapy, and passively
      exposed nonsmokers. This method avoids the need for a time-consuming and labor
      intensive sample enrichment step and thus allows for high-throughput sample
      preparation and automation.

PMID- 15472034
TI  - Assessment of urinary bone markers for monitoring treatment of osteoporosis.
AB  - BACKGROUND: The usefulness of urinary markers of bone turnover in monitoring
      therapy depends on their within-person variability compared with their responses
      to therapy. The aim of this study was to assess the performance of two such
      markers on this basis. METHODS: We measured variation, during a whole year, of
      cross-linked N-terminal telopeptide of collagen I (NTx) and urinary
      deoxypyridinoline (DPD) as ratios to creatinine concentration and after log
      transformation of the ratios in untreated women stratified into three bone
      density classes, of which the lowest was osteoporotic. We also measured changes
      in bone mineral density at the lumbar spine (LSBMD) and hip (FNBMD) in untreated
      women with normal bones and in those with moderate osteopenia and calculated the
      reference change value (RCV; or least significant change) at P <0.05 for all of
      these measures. We made the same measurements on women treated with
      bisphosphonates, estrogen replacement (HRT), or calcium and examined their
      individual responses to treatment compared with RCV. RESULTS: After 12 months on
      bisphosphonates, LSBMD changed more than RCV (2.55%) in 47% of women compared
      with 44% of those on HRT and 13% of those on calcium. Response of FNBMD was less.
      Log NTx (RCV= -28%) responded to bisphosphonates in 78%, regardless of BMD, but
      less often to HRT (67%). Log DPD (RCV= -30%) responded to bisphosphonates less
      frequently (31% at 12 months). CONCLUSIONS: NTx has advantages over DPD in
      monitoring therapy for osteoporosis when mailed urine samples are used.

PMID- 15472035
TI  - Serologic assay based on gliadin-related nonapeptides as a highly sensitive and
      specific diagnostic aid in celiac disease.
AB  - BACKGROUND: Celiac disease (CD) is induced by wheat gliadins and related cereal
      proteins. Anti-gliadin antibodies (AGAs) are present in the serum of CD patients,
      but these antibodies have lower diagnostic specificity and sensitivity than
      autoantibodies [anti-endomysium antibodies (AEmAs) and anti-tissue
      transglutaminase antibodies (AtTGAs)]. Recently, AGAs from CD patients were found
      to recognize deamidated gliadin peptides, probably formed by the action of tissue
      transglutaminase. METHODS: We synthesized several gliadin peptides and their
      glutamine-glutamic acid-substituted counterparts on cellulose membranes and
      tested their recognition by IgA in sera of 52 AEmA-positive CD patients and 76
      AEmA-negative controls in a luminescence assay. For comparison, we assayed IgA
      concentrations of AGAs, AtTGAs, and AEmAs. For measurement of AtTGAs, we used the
      human recombinant antigen. RESULTS: We identified several nonapeptides that were
      detected with high specificity by IgA in CD patients. Diagnostic accuracy of the
      peptide antibody assay was highest when peptide PLQPEQPFP was used in combination
      with peptide PEQLPQFEE within one assay. AGAs were above the cutoff in 14 of the
      controls, but only 5 of the controls were positive for peptide antibodies. For
      comparison, 82% and 94% of samples were correctly classified by AGAs and the
      combination nonapeptide assay, respectively (P = 0.007), and the AtTGAs correctly
      classified 98%. CONCLUSION: The peptide antibody assay has higher diagnostic
      accuracy than AGAs for distinguishing patients with CD from controls, and has
      diagnostic accuracy similar to that of AtTGAs.

PMID- 15472036
TI  - Detection of anti-SSA antibodies by indirect immunofluorescence.
AB  - BACKGROUND: HEp-2 cells that overexpress the human 60-kDa SSA antigen have been
      used to improve sensitivity and specificity for the detection of anti-SSA
      antibodies by indirect immunofluorescence. We describe a survey on the detection
      of anti-SSA antibodies using a commercial substrate that overexpresses SSA.
      METHODS: The evaluation was done on 18 371 consecutive samples submitted to the
      laboratory for detection of anti-nuclear antibodies, from which 188 anti-SSA
      antibody-containing and clinically documented samples were obtained. The presence
      of anti-SSA antibodies produced a distinct bright speckled pattern with nucleolar
      staining in 10-20% of interphase cells. The identity of all anti-SSA antibodies
      was confirmed by dot-blot analysis. RESULTS: Samples containing anti-SSA
      antibodies were separated into three main groups: group I, distinctive SSA
      pattern and other nuclear staining (50%); group II, only the distinctive SSA
      pattern (29%); group III, nuclear staining but without the distinctive SSA
      pattern (21%). Anti-SSA antibodies with concurrent SSB antibodies were associated
      with group I, whereas anti-SSA antibodies with concurrent U(1)-RNP antibodies
      were associated with group III. Group I included mainly patients with Sjogren
      syndrome and systemic lupus erythematosus (SLE), whereas group III included
      patients with mixed connective tissue disease and SLE. Diseases not classically
      associated with the presence of anti-SSA antibodies were found in group II in
      >50% of the cases. CONCLUSIONS: SSA-positive individuals were identified in a
      population selected on the basis of HEp-2000 positivity. Our study highlights
      diseases associated with anti-SSA antibodies and associations between the
      presence of the distinctive SSA pattern on HEp-2000 and some clinical conditions.

PMID- 15472037
TI  - Gene expression analysis in platelets from a single donor: evaluation of a PCR
      based amplification technique.
AB  - BACKGROUND: Genetic analysis of platelet mRNA may facilitate the diagnosis of
      disorders affecting the megakaryocytic-platelet lineage. Its use, however, is
      limited by the exceptionally small yield of platelet mRNA and the risk of
      leukocyte contamination during platelet preparation. METHODS: We depleted
      platelet suspensions of leukocytes by filtration and used a PCR-based RNA
      amplification step [switching mechanism at the 5' end of RNA templates (SMART)].
      We tested the reliability and precision of the RNA amplification procedure by use
      of real-time PCR to measure quantities of specific transcripts: von Willebrand
      factor (vWF), A-subunit of coagulation factor XIII (F13A), and glyceraldehyde-3
      phosphate dehydrogenase (GAPDH). Microarray analysis was performed on platelet
      RNA with and without amplification. RESULTS: Microgram quantities of platelet
      specific cDNAs were produced from as little as 50 ng of total platelet RNA or 40
      mL of whole blood. At cycle numbers <16, amplification of all transcripts tested
      was exponential with slightly more efficient amplification of low-abundance
      transcripts. Expression profiling of 9850 genes gave identical results for 9815
      genes (1576 positive/8239 negative). Eight transcripts failed to be amplified by
      the SMART procedure. Expression of vWF, F13A, and GAPDH transcripts showed only
      minor day-to-day variations in three healthy individuals. CONCLUSION: The
      proposed protocol makes extremely small amounts of platelet RNA available for
      gene expression analysis in single patients.

PMID- 15472038
TI  - Polarization observations with the Cosmic Background Imager.
AB  - Polarization observations of the cosmic microwave background with the Cosmic
      Background Imager from September 2002 to May 2004 provide a significant detection
      of the E-mode polarization and reveal an angular power spectrum of polarized
      emission showing peaks and valleys that are shifted in phase by half a cycle
      relative to those of the total intensity spectrum. This key agreement between the
      phase of the observed polarization spectrum and that predicted on the basis of
      the total intensity spectrum provides support for the standard model of
      cosmology, in which dark matter and dark energy are the dominant constituents,
      the geometry is close to flat, and primordial density fluctuations are
      predominantly adiabatic with a matter power spectrum commensurate with
      inflationary cosmological models.

PMID- 15472039
TI  - Femtomolar sensitivity of a NO sensor from Clostridium botulinum.
AB  - Nitric oxide (NO) is extremely toxic to Clostridium botulinum, but its molecular
      targets are unknown. Here, we identify a heme protein sensor (SONO) that displays
      femtomolar affinity for NO. The crystal structure of the SONO heme domain reveals
      a previously undescribed fold and a strategically placed tyrosine residue that
      modulates heme-nitrosyl coordination. Furthermore, the domain architecture of a
      SONO ortholog cloned from Chlamydomonas reinhardtii indicates that NO signaling
      through cyclic guanosine monophosphate arose before the origin of multicellular
      eukaryotes. Our findings have broad implications for understanding bacterial
      responses to NO, as well as for the activation of mammalian NO-sensitive guanylyl
      cyclase.

PMID- 15472040
TI  - Long-term aridity changes in the western United States.
AB  - The western United States is experiencing a severe multiyear drought that is
      unprecedented in some hydroclimatic records. Using gridded drought
      reconstructions that cover most of the western United States over the past 1200
      years, we show that this drought pales in comparison to an earlier period of
      elevated aridity and epic drought in AD 900 to 1300, an interval broadly
      consistent with the Medieval Warm Period. If elevated aridity in the western
      United States is a natural response to climate warming, then any trend toward
      warmer temperatures in the future could lead to a serious long-term increase in
      aridity over western North America.

PMID- 15472041
TI  - Mars' south polar Ar enhancement: a tracer for south polar seasonal meridional
      mixing.
AB  - The gamma ray spectrometer on the Mars Odyssey spacecraft measured an enhancement
      of atmospheric argon over southern high latitudes during autumn followed by
      dissipation during winter and spring. Argon does not freeze at temperatures
      normal for southern winter (approximately 145 kelvin) and is left in the
      atmosphere, enriched relative to carbon dioxide (CO2), as the southern seasonal
      cap of CO2 frost accumulates. Calculations of seasonal transport of argon into
      and out of southern high latitudes point to meridional (north-south) mixing
      throughout southern winter and spring.

PMID- 15472043
TI  - Seismology. Parkfield keeps secrets after a long-awaited quake.

PMID- 15472042
TI  - U.S. science dominance is the wrong issue.

PMID- 15472044
TI  - 2004 Nobel Prizes. Axel, Buck share award for deciphering how the nose knows.

PMID- 15472045
TI  - Climate change. Russia, reluctantly, backs Kyoto.

PMID- 15472046
TI  - Human origins. Louse DNA suggests close contact between early humans.

PMID- 15472047
TI  - Research community. Janelia Farm to recruit first class.

PMID- 15472048
TI  - Paleontology. T. rex clan evolved head first.

PMID- 15472050
TI  - Cosmology. A slanted view of the early universe.

PMID- 15472051
TI  - Astronomy. Astronomers eager for a swift new vision of the universe.

PMID- 15472049
TI  - AIDS treatment. Drugmakers test restrictions on generics in U.S. programs.

PMID- 15472053
TI  - Science education. Robotic telescopes give kids a cosmic classroom.

PMID- 15472052
TI  - Astronomy. Gamma ray bursts: new cosmic rulers?

PMID- 15472054
TI  - European science. Institute sparks an Italian renaissance in mouse biology.

PMID- 15472055
TI  - U.S. science policy. Risky business.

PMID- 15472056
TI  - Space science. Westerners put their chips on 2007 Indian moon mission.

PMID- 15472057
TI  - Ecology. Circling in on a vulture killer.

PMID- 15472058
TI  - Tropical ecosystems into the 21st century.

PMID- 15472059
TI  - Changing strategies in science education.

PMID- 15472060
TI  - Universities and the teaching of science.

PMID- 15472061
TI  - Comment on "How the horned lizard got its horns".

PMID- 15472063
TI  - Education. The evolution of postdocs.

PMID- 15472064
TI  - Molecular biology. RNAs turn on in tandem.

PMID- 15472066
TI  - Astronomy. Astronomical masers.

PMID- 15472065
TI  - Physics. The active site in nanoparticle gold catalysis.

PMID- 15472067
TI  - Applied physics. The maser at 50.

PMID- 15472068
TI  - Ecology. Keeping an eye on the neighbors.

PMID- 15472069
TI  - Development. ES cells to the rescue.

PMID- 15472071
TI  - Variable azimuthal anisotropy in Earth's lowermost mantle.
AB  - A persistent reversal in the expected polarity of the initiation of vertically
      polarized shear waves that graze the D'' layer (the layer at the boundary between
      the outer core and the lower mantle of Earth) in some regions starts at the
      arrival time of horizontally polarized shear waves. Full waveform modeling of the
      split shear waves for paths beneath the Caribbean requires azimuthal anisotropy
      at the base of the mantle. Models with laterally coherent patterns of transverse
      isotropy with the hexagonal symmetry axis of the mineral phases tilted from the
      vertical by as much as 20 degrees are consistent with the data. Small-scale
      convection cells within the mantle above the D'' layer may cause the observed
      variations by inducing laterally variable crystallographic or shape-preferred
      orientation in minerals in the D'' layer.

PMID- 15472070
TI  - Rescue of cardiac defects in id knockout embryos by injection of embryonic stem
      cells.
AB  - We report that Id knockout mouse embryos display multiple cardiac defects, but
      mid-gestation lethality is rescued by the injection of 15 wild-type embryonic
      stem (ES) cells into mutant blastocysts. Myocardial markers altered in Id mutant
      cells are restored to normal throughout the chimeric myocardium. Intraperitoneal
      injection of ES cells into female mice before conception also partially rescues
      the cardiac phenotype with no incorporation of ES cells. Insulin-like growth
      factor 1, a long-range secreted factor, in combination with WNT5a, a locally
      secreted factor, likely account for complete reversion of the cardiac phenotype.
      Thus, ES cells have the potential to reverse congenital defects through Id
      dependent local and long-range effects in a mammalian embryo.

PMID- 15472072
TI  - Estimation of fault strength: reconstruction of stress before the 1995 Kobe
      earthquake.
AB  - We have estimated the stress field before the 1995 Kobe, Japan, earthquake
      (moment magnitude 6.9) using in situ post-shock stress measurements obtained from
      hydraulic fracturing experiments near the fault. We reconstructed the pre-shock
      stress field using a kinematic source model inverted from seismic waveforms and
      geodetic deformations. We found that at the center of the fault, two sides of the
      fault surface coupled completely before the earthquake, with a coefficient of
      friction of 0.6, which is equivalent to strong crust. At the edge of the fault, a
      possible aseismic slip is expected to occur from the pre-shock stress
      orientation.

PMID- 15472073
TI  - Morphological disparity of ammonoids and the mark of Permian mass extinctions.
AB  - The taxonomic diversity of ammonoids, in terms of the number of taxa preserved,
      provides an incomplete picture of the extinction pattern during the Permian
      because of a strongly biased fossil record. The analysis of morphological
      disparity (the variety of shell shapes) is a powerful complementary tool for
      testing hypotheses about the selectivity of extinction and permits the
      recognition of three distinct patterns. First, a trend of decreasing disparity,
      ranging for about 30 million years, led to a minimum disparity immediately before
      the Permian-Triassic boundary. Second, the strongly selective Capitanian crisis
      fits a model of background extinction driven by standard environmental changes.
      Third, the end-Permian mass extinction operated as a random, nonselective sorting
      of morphologies, which is consistent with a catastrophic cause.

PMID- 15472074
TI  - The scaling of animal space use.
AB  - Space used by animals increases with increasing body size. Energy requirements
      alone can explain how population density decreases, but not the steep rate at
      which home range area increases. We present a general mechanistic model that
      predicts the frequency of interaction, spatial overlap, and loss of resources to
      neighbors. Extensive empirical evidence supports the model, demonstrating that
      spatial constraints on defense cause exclusivity of home range use to decrease
      with increasing body size. In large mammals, over 90% of available resources may
      be lost to neighbors. Our model offers a general framework to understand animal
      space use and sociality.

PMID- 15472075
TI  - Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia.
AB  - Very rare cases of human T cell acute lymphoblastic leukemia (T-ALL) harbor
      chromosomal translocations that involve NOTCH1, a gene encoding a transmembrane
      receptor that regulates normal T cell development. Here, we report that more than
      50% of human T-ALLs, including tumors from all major molecular oncogenic
      subtypes, have activating mutations that involve the extracellular
      heterodimerization domain and/or the C-terminal PEST domain of NOTCH1. These
      findings greatly expand the role of activated NOTCH1 in the molecular
      pathogenesis of human T-ALL and provide a strong rationale for targeted therapies
      that interfere with NOTCH signaling.

PMID- 15472076
TI  - A glycine-dependent riboswitch that uses cooperative binding to control gene
      expression.
AB  - We identified a previously unknown riboswitch class in bacteria that is
      selectively triggered by glycine. A representative of these glycine-sensing RNAs
      from Bacillus subtilis operates as a rare genetic on switch for the gcvT operon,
      which codes for proteins that form the glycine cleavage system. Most glycine
      riboswitches integrate two ligand-binding domains that function cooperatively to
      more closely approximate a two-state genetic switch. This advanced form of
      riboswitch may have evolved to ensure that excess glycine is efficiently used to
      provide carbon flux through the citric acid cycle and maintain adequate amounts
      of the amino acid for protein synthesis. Thus, riboswitches perform key
      regulatory roles and exhibit complex performance characteristics that previously
      had been observed only with protein factors.

PMID- 15472077
TI  - Carbonyl sulfide-mediated prebiotic formation of peptides.
AB  - Almost all discussions of prebiotic chemistry assume that amino acids,
      nucleotides, and possibly other monomers were first formed on the Earth or
      brought to it in comets and meteorites, and then condensed nonenzymatically to
      form oligomeric products. However, attempts to demonstrate plausibly prebiotic
      polymerization reactions have met with limited success. We show that carbonyl
      sulfide (COS), a simple volcanic gas, brings about the formation of peptides from
      amino acids under mild conditions in aqueous solution. Depending on the reaction
      conditions and additives used, exposure of alpha-amino acids to COS generates
      peptides in yields of up to 80% in minutes to hours at room temperature.

PMID- 15472078
TI  - Genome sequence of a polydnavirus: insights into symbiotic virus evolution.
AB  - Little is known of the fate of viruses involved in long-term obligatory
      associations with eukaryotes. For example, many species of parasitoid wasps have
      symbiotic viruses to manipulate host defenses and to allow development of
      parasitoid larvae. The complete nucleotide sequence of the DNA enclosed in the
      virus particles injected by a parasitoid wasp revealed a complex organization,
      resembling a eukaryote genomic region more than a viral genome. Although
      endocellular symbiont genomes have undergone a dramatic loss of genes, the
      evolution of symbiotic viruses appears to be characterized by extensive
      duplication of virulence genes coding for truncated versions of cellular
      proteins.

PMID- 15472079
TI  - A mechanism related to the yeast transcriptional regulator Paf1c is required for
      expression of the Arabidopsis FLC/MAF MADS box gene family.
AB  - The Arabidopsis thaliana VERNALIZATION INDEPENDENCE (VIP) gene class has multiple
      functions in development, including repression of flowering through activation of
      the MADSbox gene FLC. Epigenetic silencing of FLC plays a substantial role in the
      promotion of flowering through cold (vernalization). To better understand how VIP
      genes influence development, we undertook a genetic and molecular study of the
      previously uncharacterized VIP5 and VIP6 genes. We found that loss of function of
      these genes also resulted in downregulation of other members of the FLC/MAF gene
      family, including the photoperiodic pathway regulator MAF1/FLM. We cloned VIP5
      and VIP6 through mapping and transcriptional profiling. Both proteins are closely
      related to distinct components of budding yeast Paf1C, a transcription factor
      that assists in establishment and maintenance of transcription-promotive
      chromatin modifications such as ubiquitination of H2B by Bre1/Rad6 and
      methylation of histone H3 lysine-4 by the trithorax-related histone methylase
      Set1. Genetic analysis and coimmunoprecipitation experiments suggest that VIP5
      and VIP6 function in the same mechanism as the previously described VIP3 and
      VIP4. Our findings suggest that an evolutionarily conserved transcriptional
      mechanism plays an essential role in the maintenance of gene expression in higher
      eukaryotes and has a central function in flowering.

PMID- 15472082
TI  - Serum albumin level as a predictor of ischemic stroke outcome.

PMID- 15472080
TI  - Colocalization of L-phenylalanine ammonia-lyase and cinnamate 4-hydroxylase for
      metabolic channeling in phenylpropanoid biosynthesis.
AB  - Metabolic channeling has been proposed to occur at the entry point into plant
      phenylpropanoid biosynthesis. To determine whether isoforms of L-Phe ammonia
      lyase (PAL), the first enzyme in the pathway, can associate with the next enzyme,
      the endomembrane-bound cinnamate 4-hydroxylase (C4H), to facilitate channeling,
      we generated transgenic tobacco (Nicotiana tabacum) plants independently
      expressing epitope-tagged versions of two PAL isoforms (PAL1 and PAL2) and C4H.
      Subcellular fractionation and protein gel blot analysis using epitope- and PAL
      isoform-specific antibodies indicated both microsomal and cytosolic locations of
      PAL1 but only cytosolic localization of PAL2. However, both PAL isoforms were
      microsomally localized in plants overexpressing C4H. These results, which suggest
      that C4H itself may organize the complex for membrane association of PAL, were
      confirmed using PAL-green fluorescent protein (GFP) fusions with localization by
      confocal microscopy. Coexpression of unlabeled PAL1 with PAL2-GFP resulted in a
      shift of fluorescence localization from endomembranes to cytosol in C4H
      overexpressing plants, whereas coexpression of unlabeled PAL2 with PAL1-GFP did
      not affect PAL1-GFP localization, indicating that PAL1 has a higher affinity for
      its membrane localization site than does PAL2. Dual-labeling immunofluorescence
      and fluorescence energy resonance transfer (FRET) studies confirmed
      colocalization of PAL and C4H. However, FRET analysis with acceptor
      photobleaching suggested that the colocalization was not tight.

PMID- 15472084
TI  - Pharmaceutical interventions for emotionalism after stroke.

PMID- 15472083
TI  - Intracerebral hemorrhage: effects of aging on brain edema and neurological
      deficits.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is mostly a disease of the
      elderly, but most current experimental ICH models have used young animals. Age is
      an important factor in other forms of brain injury, affecting microglia and
      astrocyte reactions and plasticity. Therefore, the present study investigated the
      effects of aging on brain injury after ICH. METHODS: Young and aged (3 and 18
      months old, respectively) male Sprague-Dawley rats received an intracerebral
      infusion of 100 microL autologous blood. Age-related changes in brain swelling,
      glial reaction, stress protein (heat shock proteins [HSPs] 27 and 32), and
      neurological deficits were examined. RESULTS: Brain swelling was more severe in
      old rats compared with young rats at 3 days after ICH (P<0.05). There were also
      more severe neurological deficits in the older rats at 1 day after ICH, which
      persisted for the 4 weeks of monitoring (P<0.05). The older rats also had
      stronger microglial activation and a greater perihematomal induction of HSP-27
      and HSP-32 (P<0.05). In contrast, there was a weaker astrocytic reaction to the
      hematoma. CONCLUSIONS: ICH causes more severe brain swelling and neurological
      deficits in old rats. Clarification of the mechanisms of brain injury after ICH
      in the aging brain should help develop new therapeutic strategies for hemorrhagic
      brain injury.

PMID- 15472085
TI  - Relative importance of rehabilitation therapy characteristics on functional
      outcomes for persons with stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the relative
      importance of therapy focus, intensity, and length of stay on greater than
      expected functional gain, controlling for stroke severity. METHODS: This
      observational study included 198 first-stroke patients who were recruited from 8
      in-patient rehabilitation facilities and 5 subacute programs. Stroke severity
      (motor, sensory and cognitive impairment) at admission was measured using an
      instrument combining all 3 aspects; self-care, mobility, and cognitive status at
      admission and discharge were measured with the Functional Independence Measure.
      Time spent by physical, occupational, and speech-language therapists on function-
      and impairment-focused activities were used to compute therapy intensity by
      discipline and type of activity. Residual change scores, estimated by regressing
      discharge on admission functional status, were modeled using patient and therapy
      characteristics. RESULTS: Controlling for the stroke severity, greater than
      expected gains in self-care were predicted by longer lengths of stay and more
      intensive function-focused occupational therapy, and greater than expected
      cognitive gains were predicted by longer stays alone. Predictors of residual
      change in mobility, however, differed by gender: greater than expected gains in
      mobility for men were predicted by longer lengths of stay and more intense
      function-focused physical therapy whereas, for women, they were predicted by
      stroke severity alone. CONCLUSIONS: Unlike previous studies using raw functional
      gains, therapies accounted for a significant proportion of the variance in
      residual functional change. The results support studies suggesting that both
      content and amount of therapy are important aspects.

PMID- 15472086
TI  - Improved prediction of final infarct volume using bolus delay-corrected perfusion
      weighted MRI: implications for the ischemic penumbra.
AB  - BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI)-based perfusion measures
      using dynamic susceptibility contrast are extremely useful for identification of
      ischemic penumbral tissue in acute stroke. However, errors in the measurement of
      cerebral blood flow (CBF) and mean transit time (MTT) can occur. The aim of this
      study was to investigate whether bolus delay-corrected (BDC) perfusion measures
      enable better delineation of the ischemic penumbra. METHODS: Diffusion-weighted
      MRI (DWI) and perfusion-weighted MRI data were acquired from 19 acute stroke
      patients. Perfusion abnormalities were manually defined on BDC perfusion maps
      (corrected MTT [cMTT] and corrected CBF [cCBF]), and on maps derived from an
      arterial input function placed within the contralateral (CBF, MTT) and
      ipsilateral (ipsilateral CBF [iCBF] and ipsilateral MTT [iMTT]) middle cerebral
      artery. Perfusion lesion volumes were correlated with 30-day T2-weighted MRI
      lesion volumes and with clinical outcome using the National Institutes of Health
      Stroke Scale (NIHSS). RESULTS: Spearman correlation coefficients for comparing
      lesion volumes delineated on DWI, CBF, iCBF, cCBF, MTT, iMTT, and cMTT maps with
      30-day T2-weighted lesion volumes were 0.72, 0.87, 0.88, 0.90, 0.84, 0.92, and
      0.96, respectively (all P<0.001). The analogous correlation coefficients for
      comparing 30-day National Institutes of Health Stroke Scale (NIHSS) scores were
      0.39 (NS), 0.69 (NS), 0.75 (P<0.001), 0.62 (NS), 0.72 (P<0.001), 0.78 (P<0.001),
      and 0.83 (P<0.001), respectively. CONCLUSIONS: Uncorrected perfusion lesion
      volumes overestimated the extent of ischemic injury. BDC perfusion measures
      (cMTT) correlated more accurately with final lesion volume and clinical outcome.
      Such measures offer an improved estimation of the final infarct size in acute
      stroke.

PMID- 15472087
TI  - Gene transfer of extracellular superoxide dismutase failed to prevent cerebral
      vasospasm after experimental subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: We examined the therapeutic effect of human extracellular
      superoxide dismutase (ECSOD) gene transfer in the prevention of delayed cerebral
      vasospasm after experimental subarachnoid hemorrhage (SAH) because it was
      reported ECSOD relieved early-stage vasospasm. METHODS: Twenty mongrel dogs were
      divided randomly into 4 groups to serve as control, SAH, SAH+adenovirus ECSOD
      (AdECSOD), and SAH+no transgene (AdBglII) groups, respectively. An established
      canine double-hemorrhage model of SAH was used by injecting autologous arterial
      blood into the cisterna magna on day 0 and day 2. Angiography was performed at
      day 0 and day 7. Clinical behavior, cerebrospinal fluid (CSF) ECSOD activity, CSF
      leukocyte count, morphology, and human ECSOD expression (RT-PCR) in the basilar
      arteries were evaluated. RESULTS: Severe vasospasm was obtained in SAH,
      SAH+AdECSOD, and SAH+AdBglII gene-transferred dogs, and the residual diameters of
      the basilar artery were 41+/-1%, 39+/-4%, and 49+/-4%, respectively. Increased
      CSF activity of ECSOD was obtained in SAH+AdECSOD (162+/-23 U/mL) when compared
      with SAH (26+/-2) and SAH+AdBglII (25+/-3) dogs. RT-PCR confirmed successful gene
      transfer in the basilar arteries from SAH+AdECSOD dogs. Increased leukocyte
      counts were observed in the CSF and in the subarachnoid space, especially in
      SAH+AdECSOD and SAH+AdBglII dogs. CONCLUSIONS: Gene transfer of human ECSOD
      failed to prevent delayed cerebral vasospasm.

PMID- 15472088
TI  - Thoughts evoked by MATCH and other trials.

PMID- 15472089
TI  - Are there genetic influences on sporadic brain arteriovenous malformations?
AB  - The genesis of brain arteriovenous malformations remains enigmatic. We reviewed
      some pathways involving inflammatory and angiogenic signals that are amenable to
      the study of genetic single-nucleotide polymorphisms associated with the sporadic
      disease. Such study can yield insights into arteriovenous malformation
      pathogenesis and suggest possible fruitful approaches to developing medical
      therapy. Moreover, single-nucleotide polymorphisms identification would provide
      targets for risk stratification for planning clinical trials and eventually
      guiding management.

PMID- 15472090
TI  - Should the MATCH results be extrapolated to all stroke patients and affect
      ongoing trials evaluating clopidogrel plus aspirin?

PMID- 15472091
TI  - Blood vessel function and cognition in elderly patients with atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Although a strong relationship has been established
      between vascular disease and cognitive decline, the current challenge is to
      identify vascular risk factors and mechanisms that are associated with cognitive
      function before the development of severe dysfunction (eg, vascular dementia).
      This study was conducted to determine the relationship between blood vessel
      function and cognition in elderly patients with atherosclerosis. METHODS:
      Participants were 14 elderly individuals with atherosclerotic vascular disease,
      who had no history of stroke, cardiac surgery, or dementia diagnosis. Forearm
      blood flow was measured before and after brachial artery infusion of 3 vasoactive
      agents (verapamil, acetylcholine, nitroprusside), and these measures of vessel
      function were then correlated with neuropsychological performance (total scale
      score on the Repeatable Battery for the Assessment of Neuropsychological Status).
      RESULTS: Positive correlations were found between neuropsychological performance
      and vasodilation in response to all 3 agents, with 2 reaching statistical
      significance (verapamil: rho=0.78, P=0.001; nitroprusside: rho=0.56, P=0.038) and
      the third showing a strong trend toward significance (acetylcholine: rho=0.49,
      P=0.076). Correlations between neuropsychological performance and more
      conventional vascular-related variables were much weaker. CONCLUSIONS: These data
      provide preliminary evidence of a relationship between resistance vessel function
      and neuropsychological performance. With further research, measures of vessel
      dysfunction may be useful in identifying individuals at risk for cognitive
      decline and vascular dementia.

PMID- 15472092
TI  - Scanning laser Doppler flowmetry shows reduced retinal capillary blood flow in
      CADASIL.
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) is a progressive systemic
      nonatherosclerotic angiopathy which causes ischemic strokes and vascular
      subcortical dementia. A cross-sectional study was performed to examine the
      retinal vascular caliber and blood flow in CADASIL. METHODS: Scanning laser
      Doppler flowmetry was used in a case-control study (11 patients and controls) of
      peripapillary retinal circulation. Automated full-field perfusion image analysis
      was used to analyze the flow data. Retinal vessel calibers were measured from
      retinal images acquired with scanning laser ophthalmoscopy. The caliber of the
      superior and inferior temporal retinal artery and vein were measured 1 and 2 mm
      from the disc rim, and the mean values were used for analysis. RESULTS: Retinal
      capillary peak systolic flow (mean, 249 versus 311 arbitrary unit [AU]; P=0.072)
      was lower, and mean capillary flow (mean, 184 versus 224 AU; P=0.12) and minimum
      diastolic flow (mean, 105 versus 132 AU; P=0.16) tended to be lower in patients
      than in controls. No significant difference in the calibers of proximal retinal
      arteries (mean, 104 versus 108 microm) and veins (mean, 150 versus 145 microm)
      was found between the patients and controls. CONCLUSIONS: Retinal capillary blood
      flow is mild to moderately reduced in CADASIL but that does not appear to cause
      major ischemic injury. Such reduction is analogous to that in the cerebral cortex
      in CADASIL patients with which retina appears to share its relative sparing from
      severe arterial ischemic tissue damage.

PMID- 15472093
TI  - The need to recognize the difference between a quality register and a randomized
      controlled trial.

PMID- 15472094
TI  - Determination of carotid artery atherosclerotic lesion type and distribution in
      hypercholesterolemic patients with moderate carotid stenosis using noninvasive
      magnetic resonance imaging.
AB  - BACKGROUND AND PURPOSE: The aims of this study were to noninvasively determine
      carotid atherosclerotic lesion type and distribution and to evaluate the
      reproducibility of determining lesion types in asymptomatic patients with
      moderate hypercholesterolemia and moderate carotid artery (CA) stenosis using
      MRI. METHODS: Forty-two asymptomatic patients with moderate CA stenosis underwent
      bilateral carotid MRI in a 1.5-T scanner using a protocol that generated 4
      contrast weightings (T1, T2, proton density, and 3D time of flight). MRI-modified
      American Heart Association criteria were used to evaluate lesion types at 3
      locations (common and internal CA [CCA and ICA, respectively] and CA bifurcation)
      and at the minimum lumen area. Two identical MR scans were conducted to evaluate
      reproducibility of lesion types. RESULTS: Lesion types were obtained from 230
      locations. Type III (39%) occurred most commonly, followed by types IV-V (25%), I
      II (20%), VI (12%), and VII (4%). Type III was more commonly distributed in the
      CCA (n=35, 39%) and ICA (n=32, 36%). Type IV-V was more commonly distributed in
      the CCA (n=24, 41%) and at the bifurcation (n=21, 36%). Forty-two lesions were
      available at the site of minimum lumen area: type III (33%), IV-V (33%), VI
      (29%), and VII (5%). There was good agreement of lesion types between both MRI
      scans (Cohen's kappa=0.73; 95% CI: 0.65 to 0.81). CONCLUSIONS: MRI can determine
      lesion types reproducibly as well as the distribution of lesions in
      hypercholesterolemic patients with moderate CA stenosis. A wide range of lesion
      types, including advanced lesions, were found in these patients.

PMID- 15472095
TI  - Faster is better: implications for speed-intensive gait training after stroke.
AB  - BACKGROUND AND PURPOSE: The instantaneous adaptations to speed and load changes
      during overground locomotion have major implications for mobility after stroke.
      We examined the extent to which stroke subjects could increase their overground
      walking speed with respect to speed and unloading changes. METHODS: Twelve
      subjects with a unilateral stroke were evaluated while walking overground full
      weight bearing (FWB) or with body weight support (BWS) at preferred or fast
      speed. On the basis of their preferred walking speed, subjects were classified as
      high (> or =45 cm/s) or low functioning (<45 cm/s). Gait speed, temporal distance
      factors (TDFs), as well as movements and muscle activation of the lower limbs
      were measured and compared across the conditions. RESULTS: FWB-Fast condition
      induced marked (165%) increment in gait speed in all subjects. BWS at preferred
      speed induced faster speeds in low- but not the high-functioning subjects,
      whereas combined BWS and fast walking yielded further speed increments in the
      high-functioning subjects. Fast walking was associated with bilateral increases
      in joint excursion and muscle activation, as well as improved symmetry in some
      TDFs. BWS favored a hip flexion strategy in early swing while decreasing limb
      circumduction. CONCLUSIONS: This study shows that stroke subjects can increase
      substantially their walking speed without deleterious effects. Fast walking
      induces marked speed-related improvements in body and limb kinematics and muscle
      activation patterns. BWS during overground walking also increases gait speed, but
      to a lesser extent and only in low-functioning subjects. The combination of BWS
      with fast speed produces the greatest increments in walking speed in all
      subjects.

PMID- 15472096
TI  - Stroke incidence and 30-day case-fatality in a suburb of Tbilisi: results of the
      first prospective population-based study in Georgia.
AB  - BACKGROUND AND PURPOSE: Although stroke is one of the main public health problems
      worldwide, no study of stroke incidence has been performed in Georgia, and
      therefore, a population-based registry was established to determine the incidence
      and case-fatality rates of first-ever stroke. METHODS: We identified all first
      ever strokes between November 2000 and July 2003 in a defined population of
      51,246 residents in the Sanzona suburb of Tbilisi, the capital of Georgia, using
      overlapping sources of information and standard diagnostic criteria. RESULTS: A
      total of 233 first-ever strokes occurred during the study period. The crude
      annual incidence rate was 165 (95% CI, 145 to 188) per 100,000 residents. The
      corresponding rate adjusted to the standard "world" population was 103 (95% CI,
      89 to 117). In terms of stroke subtype, the crude annual incidence rate per
      100,000 inhabitants was 89 (95% CI, 74 to 106) for ischemic stroke, 44 (95% CI,
      34 to 57) for intracerebral hemorrhage, 16 (95% CI, 10 to 25) for subarachnoidal
      hemorrhage, and 16 (95% CI, 10 to 25) for unspecified stroke, and the
      corresponding case-fatality rates at 1 month were 19.2%, 48.4%, 47.8%, and 69.6%.
      CONCLUSIONS: The overall stroke incidence rate in an urban population of Georgia
      is comparable to those reported in developed countries. As for the stroke
      subtypes, there is an excess of hemorrhagic strokes compared with other
      registries. Geographical and lifestyle variations may explain these findings,
      whereas inadequacy of the stroke care system in Georgia might contribute to the
      high case-fatality.

PMID- 15472097
TI  - Neurotoxicity of intra-arterial papaverine preserved with chlorobutanol used for
      the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Papaverine is used to vasodilate cerebral arteries
      undergoing vasospasm from subarachnoid hemorrhage. However, papaverine inhibits
      cellular respiration in vitro and could cause neurotoxicity in humans. METHODS:
      We studied 5 consecutive patients with cerebral vasospasm who were treated with
      intra-arterial papaverine preserved with chlorobutanol and imaged with MRI fluid
      attenuated inversion recovery and diffusion-weighted imaging after treatment. One
      patient had histological analysis of the brain at autopsy. RESULTS: All 5
      patients exhibited marked neurological decline immediately after treatment, and
      this was sustained through hospital discharge. In all cases, MRI images showed
      selective gray matter-only signal changes within the vascular territory treated
      with papaverine. Histological analysis of 1 case brought to autopsy showed
      selective injury to islands of neurons with relative sparing of white matter.
      CONCLUSIONS: Intra-arterial delivery of papaverine preserved with chlorobutanol
      into vasospastic anterior cerebral arteries may result in marked neurological
      deterioration with selective gray matter changes on MRI imaging. This effect is
      consistent with a permanent toxic effect to human brain. It is unclear whether
      this toxicity is caused by papaverine or chlorobutanol, and its use in the
      treatment of cerebral vasospasm should be reserved for cases without
      alternatives.

PMID- 15472098
TI  - Inflammatory gene load is associated with enhanced inflammation and early carotid
      atherosclerosis in smokers.
AB  - BACKGROUND AND PURPOSE: Smoking acts as a pro-inflammatory stimulus. Inflammation
      may provide a key mechanism by which smoking causes atherosclerosis. If so, then
      the degree to which an individual mounts an inflammatory response is likely to
      influence atherosclerosis severity. This study examined the impact of
      inflammatory gene polymorphisms and gene-smoking interactions on common carotid
      artery intima-media thickness (IMT), a measure of early atherosclerosis. METHODS:
      In a community population (n=1000), mean IMT was determined using ultrasound.
      This population was genotyped for 6 polymorphisms in 4 inflammatory genes: IL-6
      174, IL-6-572, and IL-6-597; IL-1-beta-31; IL-1 receptor antagonist VNTR and CD14
      159. Serum IL-6 levels were measured in the first 500 subjects.
      Genotypes/haplotypes associated with higher IL-6 levels were designated
      "inflammatory haplotypes." A gene load score was calculated, in which 2
      represented individuals homozygous for > or =2 inflammatory genotypes/haplotypes
      and 0 was homozygous for none. RESULTS: Increasing gene load of inflammatory
      genotypes was associated with a linear increase in serum IL-6 levels (P=0.018)
      and increased carotid artery IMT (P=0.003). There was a significant interaction
      between gene load and smoking status on carotid IMT (P for interaction=0.002).
      Specifically, in smokers, carriers of inflammatory haplotypes had significantly
      increased age- and sex-adjusted IMT (IL-6-174C/IL-6-572G/IL-6-597A, P=0.005; IL-1
      beta-31T/IL-1RN*2,P=0.04; CD14-159CC, P=0.028). CONCLUSIONS: These findings
      support the hypothesis that inflammation and cytokine responses provide a key
      mechanism by which smoking causes atherogenesis. Secondly, they highlight the
      importance of gene-environment, and gene-gene-environment interactions in the
      pathogenesis of atherosclerosis.

PMID- 15472099
TI  - Early vasospasm on admission angiography in patients with aneurysmal subarachnoid
      hemorrhage is a predictor for in-hospital complications and poor outcome.
AB  - BACKGROUND AND PURPOSE: Early vasospasm (EVSP), defined here as arterial
      narrowing seen on diagnostic angiography within the first 48 hours of aneurysmal
      rupture, is a rarely reported and poorly defined phenomenon in patients with
      subarachnoid hemorrhage (SAH). The purpose of this study was to characterize EVSP
      in a large database of such patients. METHODS: We analyzed the relationship of
      EVSP to clinical characteristics, in-hospital complications, and outcome at 3
      months among 3478 patients entered into 4 prospective, randomized, double-blind,
      placebo-controlled trials of tirilazad conducted in neurosurgical centers around
      the world between 1991 and 1997. RESULTS: Three hundred thirty-nine (10%) of 3478
      patients had EVSP. EVSP was significantly more likely in patients with poor
      neurological grade on admission, history of SAH, intracerebral hematoma, larger
      aneurysm, thick SAH on cranial computed tomography, and intraventricular
      hemorrhage. EVSP was not associated with delayed cerebral vasospasm. After
      adjustment for differences in admission characteristics, EVSP was associated with
      cerebral infarction (adjusted odds ratios [OR]=1.51; 95% CI, 1.18 to 1.94;
      P=0.001), neurological worsening (OR=1.41; 95% CI, 1.10 to 1.81; P=0.007), and
      unfavorable outcome (OR=1.51; 95% CI, 1.15 to 2.00; P=0.003). In addition, there
      was a trend for patients with increasingly severe EVSP to have unfavorable
      outcome (OR=1.84 for mild and OR=2.66 for moderate/severe EVSP). CONCLUSIONS:
      EVSP was seen in 10% of SAH patients and was predictive of cerebral infarction
      and neurological worsening as well as unfavorable outcome at 3 months. EVSP was
      not associated with late vasospasm. EVSP may be as important as delayed vasospasm
      in predicting complications and long-term morbidity in SAH patients.

PMID- 15472100
TI  - Oxidative stress affects the integrin-linked kinase signaling pathway after
      transient focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: The integrin-linked kinase (ILK) signaling pathway
      contributes to regulation of cellular adhesion, migration, and differentiation,
      and to apoptotic cell death after a variety of cell death stimuli. We have
      reported that overexpression of copper/zinc superoxide dismutase (SOD1) reduces
      apoptotic cell death by promoting the phosphatidylinositol 3-kinase (PI3-K)/Akt
      survival pathway after transient focal cerebral ischemia (tFCI). However, the
      role of the ILK pathway after tFCI and the role of oxygen free radicals in
      regulation of apoptosis remain unclear. METHODS: To clarify these issues, we used
      an in vivo tFCI model with SOD1 transgenic mice and wild-type mice. We
      administered the PI3-K inhibitor, LY294002, into mouse brains after tFCI and
      examined the role of PI3-K in the ILK pathway and expression of the ILK/Akt
      complex by immunohistochemistry, Western blot analysis, and
      coimmunoprecipitation. RESULTS: A transient increase in ILK was detected early
      after tFCI and was prevented by treatment with LY294002, but promoted by SOD1.
      Coimmunoprecipitation revealed that the direct reaction of ILK/Akt transiently
      increased concurrent with the increase in ILK after tFCI. Moreover, the ILK/Akt
      complex was prevented by LY294002, but promoted by SOD1. CONCLUSIONS: These
      results suggest that the ILK pathway mediated by PI3-K is affected by tFCI and by
      SOD1.

PMID- 15472101
TI  - Enhanced motor cortex excitability during ipsilateral voluntary hand activation
      in healthy subjects and stroke patients.
AB  - BACKGROUND AND PURPOSE: It is still a matter of debate whether the ipsilateral
      voluntary hand activation has a facilitatory or inhibitory effect on the
      nondominant or affected hemisphere. To give an answer to this question is of
      great importance for the rehabilitation of stroke patients, because they often
      use the unaffected hand for compensation. METHODS: Ten healthy volunteers and 11
      stroke patients were investigated using transcranial magnetic stimulation (TMS).
      TMS was applied to the dominant/unaffected hemisphere during performance of
      different tasks (simple index finger abduction, pinch grip, and power grip) at
      various force levels (5%, 10%, 50%, and 100% maximal voluntary contraction) with
      the ipsilateral hand. Peak-to-peak amplitudes of motor-evoked potentials were
      used as measure for motor cortex excitability. RESULTS: Both simple and complex
      tasks led to a facilitation of the contralateral corticospinal system at all
      levels of applied force. Not only the facilitatory effect in general but also the
      slope of the relationship between force level and MEP amplitude were
      significantly lower in stroke patients indicating that both the general
      activation level of the impaired motor system and the bandwidth of possible
      activation levels are diminished. CONCLUSIONS: Voluntary activation of the hand
      does not exert an inhibitory effect on the excitability of the ipsilateral
      hemisphere in healthy volunteers or in stroke patients.

PMID- 15472102
TI  - Continuous quantitative EEG monitoring in hemispheric stroke patients using the
      brain symmetry index.
AB  - BACKGROUND AND PURPOSE: There is increased awareness that continuous brain
      monitoring might benefit neurological patients, because it may allow detection of
      derangement of brain function in a possible reversible state, allowing early
      intervention. Here, we explore if quantitative continuous electroencephalography
      (cEEG) monitoring is technically feasible and possibly clinically relevant in
      patients with acute ischemic hemispheric stroke.Materials- Twenty-one consecutive
      patients with an acute hemispheric stroke were monitored in our stroke unit,
      using cEEG for 12 to 24 hours on the day of admission. EEGs were quantified using
      a particular measure for symmetry, the brain symmetry index (BSI). This measure
      was subsequently correlated with the clinical condition of the patient using the
      National Institute of Health Stroke Scale (NIHSS). RESULTS: cEEG was technically
      feasible. We found a most satisfying positive correlation between the BSI and the
      NIHSS, with rho approximately 0.86 (P<0.01). CONCLUSIONS: Technically, cEEG
      monitoring posed no major problems. It was found that the BSI correlates
      satisfactorily with the clinical neurological condition of our stroke patients.
      This suggests that the BSI can be used as a measure to monitor possible changes
      of brain function in this patient category.

PMID- 15472104
TI  - Angiotensinogen promoter B-haplotype associated with cerebral small vessel
      disease enhances basal transcriptional activity.
AB  - BACKGROUND AND PURPOSE: Previously, we described the presence of 5 haplotypes (A
      to E) at the angiotensinogen (AGT) promoter and reported a significant
      association between the B-haplotype (nucleotide substitutions -6:G-->A and -20:A-
      >C compared with the wild-type A-haplotype) and magnetic resonance imaging
      correlates of cerebral small vessel disease (cSVD). The association was
      independent of hypertension, suggesting a brain-specific effect of this
      haplotype. In the current study, we investigated transcriptional activities of
      the 5 promoter haplotypes in astrocytes, the main source of cerebral AGT, and in
      hepatocytes, the main source of systemic AGT, as well as determined the
      evolutionary relatedness of the promoter haplotypes. METHODS: Transcriptional
      activity depending on the haplotypes and the -6:A and -20:C substitutions was
      measured in transiently transfected A172 and HepG2 cells. We genotyped 5 new
      single nucleotide polymorphisms (SNPs) at the AGT gene and measured linkage
      disequilibrium (LD) among SNPs and the promoter haplotypes. An evolution-based
      haplotype tree was constructed. RESULTS: The B-haplotype increased
      transcriptional activity in both cell types. Its effect was stronger in
      astrocytes than in hepatocytes (2.4+/-0.09-fold, P<0.001 versus 1.6+/-0.06-fold,
      P=0.014). Importantly, in astrocytes the combination of the -6:A and the -20:C
      was mandatory for increased activity, whereas in hepatocytes the -20:C on its own
      was sufficient. Strong LD between the 5 new SNPs and the promoter haplotypes
      allowed the reconstruction of 9 haplotypes over the AGT gene. Cladistic analyses
      suggest that the B-haplotype represents an ancient promoter variant. CONCLUSIONS:
      Combination of the -6:A and -20:C substitutions in the B-haplotype may promote
      the development of cSVD by enhancing cerebral angiotensinogen expression.

PMID- 15472105
TI  - Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human
      focal brain ischemia using a novel imaging marker of early blood-brain barrier
      disruption.
AB  - Loss of integrity of the blood-brain barrier (BBB) resulting from ischemia and
      reperfusion is a hypothesized precursor to hemorrhagic transformation (HT) and
      worse clinical outcome than would be expected from the beneficial effects of
      reperfusion. We used a novel magnetic resonance imaging marker to characterize
      early BBB disruption in acute focal brain ischemia and tested associations with
      reperfusion, HT, and poor outcome (modified Rankin score >2). The BBB disruption
      was evident as delayed gadolinium enhancement of cerebrospinal fluid space on
      fluid-attenuated inversion recovery (FLAIR) images and, for convenience, has been
      termed hyperintense acute reperfusion marker (HARM). HARM was found in 47 of 144
      (33%) ischemic stroke patients. Reperfusion was found to be the strongest
      independent predictor of early BBB disruption (P=0.018) in multivariate analysis.
      HARM was associated with HT and worse clinical outcome (after adjustment for
      initial severity). It was also associated with more severe strokes at onset and
      greater age. Because the timing of the disruption was early enough (median
      estimate 3.8 hours from onset) to make it relevant to acute thrombolytic therapy,
      early BBB disruption as defined by HARM may be a promising target for adjunctive
      therapy to reduce the complications associated with thrombolytic therapy, broaden
      the therapeutic window, and improve clinical outcome.

PMID- 15472106
TI  - Immunogenetic susceptibility of atherosclerotic stroke: implications on current
      and future treatment of vascular inflammation.
AB  - The understanding of the pathophysiology governing atherosclerosis supports a
      prominent role for inflammation pathways in plaque initiation and progression
      that result in stroke and myocardial infarction. Elevated levels of inflammatory
      markers in the blood, such as C-reactive protein and CD40 ligand/CD40, in concert
      with increased expression of adhesion molecules, chemokines, cytokines, matrix
      metalloproteinases (MMP), and inflammatory cells in the plaque, characterize the
      symptomatic atherothrombotic state. Advances in predictive capabilities of
      vascular events using a number of these biomarkers are beginning to remodel our
      clinical practice in the use of medications such as statins and angiotensin
      receptor blockers for stroke prevention. Although the general inflammatory
      features of atherosclerosis are becoming widely recognized, factors resulting in
      individual variability in plaque formation and instability remain poorly defined.
      Emerging literature points toward several acquired and innate susceptibility
      factors in the immune pathways that may provide insight into why many plaques
      rapidly evolve from a "stable" to an "unstable" or symptomatic state. First,
      exposure of plaque memory T-lymphocytes to infectious or endogenous antigens may
      result in rapid clonal expansion of T-cell variable beta chain subtypes and
      stimulate macrophages to release MMPs, causing plaque destabilization. The
      effects of infectious agents can further be influenced by an individual's major
      histocompatibility complex class II molecule profiles, which can affect
      susceptibility to specific organisms. Second, functional polymorphisms of genes
      that regulate the immune pathway can predispose patients to a more robust
      inflammatory expression after risk factor exposure. Identification of a
      susceptibility gene profile and immunologic mediators that promote T-cell
      activation provides a unique opportunity for early identification of stroke risk
      and targets for future therapy.

PMID- 15472107
TI  - Estrogen-like compounds for ischemic neuroprotection.
AB  - We have synthesized a library of estrogen analogues, including enantiomers of
      estradiol and A-ring substituted estrogens. These compounds have reduced or no
      binding to either estrogen receptor-alpha or estrogen receptor-beta, exhibit
      enhanced neuroprotective activity in in vitro models, and are potent in
      protecting brain tissue from cerebral ischemia/reperfusion injury. These potent,
      nonfeminizing estrogen analogues are prime candidates for use in stroke
      neuroprotection.

PMID- 15472108
TI  - Two sodium/calcium exchanger gene products, NCX1 and NCX3, play a major role in
      the development of permanent focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: The Na+/Ca2+ exchanger, by mediating Ca2+ and Na+ fluxes
      in a bidirectional way across the synaptic plasma membrane, may play a pivotal
      role in the events leading to anoxic damage. In the brain, there are 3 different
      genes coding for 3 different proteins: NCX1, NCX2, and NCX3. The aim of this
      study was to determine whether NCX1, NCX2, and NCX3 might play a differential
      role in the development of cerebral injury induced by permanent middle cerebral
      artery occlusion (pMCAO). METHODS: By means of Western blotting, NCX1, NCX2, and
      NCX3 protein expression was evaluated in the ischemic core and in the remaining
      nonischemic area of the slice at different time intervals starting from ischemia
      induction. The role of each isoform was also assessed with antisense
      oligodeoxynucleotides (ODNs) targeted for each isoform. These ODNs were
      continuously intracerebroventricularly infused with an osmotic minipump (1
      microL/h) for 48 hours, 24 hours before pMCAO. RESULTS: The results showed that
      after pMCAO all 3 NCX proteins were downregulated in ischemic core; NCX3
      decreased in periinfarctual area whereas NCX1 and NCX2 were unchanged. The ODNs
      for NCX1 and NCX3 gene products were capable of inducing an increase in the
      ischemic lesion and to worsen neurological scores. CONCLUSIONS: The results of
      this study suggest that in the neuroprotective effect exerted by NCX during
      ischemic injury, the major role is prevalently exerted by NCX1 and NCX3 gene
      products.

PMID- 15472110
TI  - Impact of admission hyperglycemia on stroke outcome after thrombolysis: risk
      stratification in relation to time to reperfusion.
AB  - BACKGROUND AND PURPOSE: We evaluated the impact of admission hyperglycemia (HG)
      on stroke outcome in relation to the timing of reperfusion in patients treated
      with tissue plasminogen activator (tPA). METHODS: We studied 138 consecutive
      stroke patients with a documented middle cerebral artery (MCA) occlusion treated
      with intravenous tPA <3 hours of stroke onset. Serum glucose was determined at
      baseline before tPA administration. HG was defined as a glucose level >140 mg/dL.
      National Institutes of Health Stroke Scale (NIHSS) scores were obtained at
      baseline and 24 hour. Transcranial Doppler monitoring of recanalization was
      conducted during the first 12 hour of stroke onset. mRS was used to assess
      outcome at 3 months. RESULTS: Median baseline NIHSS score was 17 points. At
      baseline, 42 (37.3%) patients were hyperglycemic and 96 (62.7%) normoglycemic.
      Reperfusion was achieved <3 hours of stroke onset in 32 (23%) patients, between 3
      to 6 hours in 49 (36%), 6 to 12 hours in 15 (12%), and in 32 (23%) the MCA
      remained occluded at 12 hours. A logistic regression model revealed that baseline
      NIHSS score >16 points (odds ratio [OR], 3.32; 95% CI, 2.18 to 24.7; P=0.032) and
      admission glucose level >140 mg/dL (OR, 5.65; 95% CI, 1.97 to 16.18; P=0.002)
      independently predicted poor outcome (modified Rankin scale, 3 to 6) at 3 months.
      After adjusting by age, stroke severity, site of MCA occlusion, and degree of
      recanalization, the contribution of HG for poor outcome was higher as shorter the
      time to reperfusion. The highest odds for poor outcome related to HG corresponded
      to patients who recanalized <3 hour (OR, 3.1; 95% CI, 1.8 to 14.3; P=0.002), as
      compared with those who recanalized between 3 and 6 hours (OR, 2.1; 95% CI, 1.1
      to 16; P=0.034) and between 6 to 12 hours (OR, 1.1; 95% CI, 0.7 to 21; P=0.43).
      Moreover, baseline glucose level was negatively correlated (r=-0.45; P=0.001)
      with the degree of improvement in the NIHSS score at 24 hours after early (<3
      hours) but not after delayed (>3 hours) or no recanalization. CONCLUSIONS: The
      impact of admission HG on stroke outcome varies depending on the time to tPA
      induced reperfusion. The detrimental effect of acute HG is higher after early
      than after delayed or no reperfusion. Ultra-early glycemic control before
      reperfusion may improve the efficacy of thrombolytic therapy.

PMID- 15472111
TI  - White matter lesions and glial activation in a novel mouse model of chronic
      cerebral hypoperfusion.
AB  - BACKGROUND AND PURPOSE: Cerebrovascular white matter (WM) lesions are closely
      associated with cognitive impairment and gait disorders in the elderly. We have
      successfully established a mouse model of chronic cerebral hypoperfusion that may
      provide new strategies for the molecular analysis of cerebrovascular WM lesions.
      METHODS: Adult C57Bl/6 male mice were subjected to bilateral common carotid
      artery stenosis (BCAS) using external microcoils with varying inner diameters
      from 0.16 to 0.22 mm. Cerebral blood flow (CBF) in the frontal cortices was
      measured by laser-Doppler flowmetry at 2 hours and at 1, 3, 7, 14, and 30 days
      after BCAS. The brains were then removed and examined at 30 days with
      histological stains and immunohistochemistry for markers of microglia and
      astroglia. RESULTS: At 2 hours, the CBF values (ratio to the preoperative value)
      did not change in the 0.22 mm group but decreased significantly to 77.3+/-13.4%
      in the 0.20 mm group, 67.3+/-18.5% in the 0.18 mm group, and 51.4+/-11.5% in the
      0.16 mm group. At day 1, the CBF began to recover in all groups but remained
      significantly lower until 14 days in comparison to the control group. In the 0.20
      mm and 0.18 mm groups, WM lesions occurred after 14 days without any gray matter
      involvement. These lesions were the most intense in the corpus callosum adjacent
      to the lateral ventricle but were mild in the anterior commissure and optic
      tract. In contrast, 4 of 5 mice developed some gray matter changes in the 0.16 mm
      group. The proliferation of activated microglia and astroglia was observed in the
      WM beyond 3 days after BCAS. CONCLUSIONS: WM lesions were successfully induced
      after chronic cerebral hypoperfusion with relative preservation of the visual
      pathway. These features in this mouse model are appropriate for cognitive
      assessment and genetic analysis, and it may provide a powerful tool to understand
      the pathophysiology of WM lesions.

PMID- 15472112
TI  - Evolving paradigms in neuroimaging of the ischemic penumbra.
AB  - Identification of the ischemic penumbra in the acute stroke clinical setting is
      an important goal for stroke researchers and clinicians. Various models for
      imaging the penumbra with MRI have been proposed, including the pioneering
      diffusion-perfusion mismatch model and later multivariate approaches. A number of
      multicenter clinical trials are now under way to test these models and confirm
      the utility of MRI-based treatment decisions. Present knowledge about MRI
      visualization of the salvageable penumbra suggests a promising future in which
      MRI studies are performed routinely in the acute stroke setting and the data
      provided by these MRI studies assist in individualizing therapeutic decisions and
      identifying effective therapies that can be delivered at late time points.

PMID- 15472113
TI  - Translation of ischemic preconditioning to the patient: prolyl hydroxylase
      inhibition and hypoxia inducible factor-1 as novel targets for stroke therapy.
AB  - Effective therapies for stroke must interdict multiple parallel and sequential
      pathophysiological events. A paradigm which offers insight into multivalent but
      thoughtfully coordinated protective programs is ischemic preconditioning. A
      central hypothesis of our group and others is that pharmacological agents that
      activate programs of gene expression normally induced by ischemic preconditioning
      will be effective agents for the prevention and treatment of stroke. Inhibitors
      of a class of enzymes, the hypoxia inducible factor-1 (HIF-1) prolyl hydroxylases
      stabilize the transcriptional activator HIF-1 and activate target genes involved
      in compensation for ischemia, including erythropoeitin (Epo) and vascular
      endothelial growth factor (VEGF). Here, we review evidence suggesting that the
      HIF-1 prolyl hyroxylases are inhibited during ischemic preconditioning and that
      pharmacological inhibitors of these enzymes are viable targets for stroke
      therapy.

PMID- 15472114
TI  - Effects of augmented exercise therapy time after stroke: a meta-analysis.
AB  - BACKGROUND AND PURPOSE: To present a systematic review of studies that addresses
      the effects of intensity of augmented exercise therapy time (AETT) on activities
      of daily living (ADL), walking, and dexterity in patients with stroke. SUMMARY OF
      REVIEW: A database of articles published from 1966 to November 2003 was compiled
      from MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, PEDro,
      DARE, and PiCarta using combinations of the following key words: stroke,
      cerebrovascular disorders, physical therapy, physiotherapy, occupational therapy,
      exercise therapy, rehabilitation, intensity, dose-response relationship,
      effectiveness, and randomized controlled trial. References presented in relevant
      publications were examined as well as abstracts in proceedings. Studies that
      satisfied the following selection criteria were included: (1) patients had a
      diagnosis of stroke; (2) effects of intensity of exercise training were
      investigated; and (3) design of the study was a randomized controlled trial
      (RCT). For each outcome measure, the estimated effect size (ES) and the summary
      effect size (SES) expressed in standard deviation units (SDU) were calculated for
      ADL, walking speed, and dexterity using fixed and random effect models.
      Correlation coefficients were calculated between observed individual effect sizes
      on ADL of each study, additional time spent on exercise training, and
      methodological quality. Cumulative meta-analyses (random effects model) adjusted
      for the difference in treatment intensity in each study was used for the trials
      evaluating the effects of AETT provided. Twenty of the 31 candidate studies,
      involving 2686 stroke patients, were included in the synthesis. The
      methodological quality ranged from 2 to 10 out of the maximum score of 14 points.
      The meta-analysis resulted in a small but statistically significant SES with
      regard to ADL measured at the end of the intervention phase. Further analysis
      showed a significant homogeneous SES for 17 studies that investigated effects of
      increased exercise intensity within the first 6 months after stroke. No
      significant SES was observed for the 3 studies conducted in the chronic phase.
      Cumulative meta-analysis strongly suggests that at least a 16-hour difference in
      treatment time between experimental and control groups provided in the first 6
      months after stroke is needed to obtain significant differences in ADL. A
      significant SES supporting a higher intensity was also observed for instrumental
      ADL and walking speed, whereas no significant SES was found for dexterity.
      CONCLUSIONS: The results of the present research synthesis support the hypothesis
      that augmented exercise therapy has a small but favorable effect on ADL,
      particularly if therapy input is augmented at least 16 hours within the first 6
      months after stroke. This meta-analysis also suggests that clinically relevant
      treatment effects may be achieved on instrumental ADL and gait speed.

PMID- 15472115
TI  - Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits
      angiogenesis in preeclampsia.
AB  - Preeclampsia is an inflammatory disorder in which serum levels of vascular
      endothelial growth factor (VEGF) and its soluble receptor-1 (sVEGFR-1, also known
      as sFlt-1) are elevated. We hypothesize that VEGF and placenta growth factor
      (PlGF) are dysregulated in preeclampsia due to high levels of sVEGFR-1, which
      leads to impaired placental angiogenesis. Analysis of supernatants taken from
      preeclamptic placental villous explants showed a four-fold increase in sVEGFR-1
      than normal pregnancies, suggesting that villous explants in vitro retain a
      hypoxia memory reflecting long-term fetal programming. The relative ratios of
      VEGF to sVEGFR-1 and PlGF to sVEGFR-1 released from explants decreased by 53% and
      70%, respectively, in preeclampsia compared with normal pregnancies. Exposure of
      normal villous explants to hypoxia increased sVEGFR-1 release compared with
      tissue normoxia (P<0.001), as did stimulation with tumor necrosis factor-alpha
      (P<0.01). Conditioned medium (CM) from normal villous explants induced
      endothelial cell migration and in vitro tube formation, which were both
      attenuated by pre-incubation with exogenous sVEGFR-1 (P<0.001). In contrast,
      endothelial cells treated with preeclamptic CM showed substantially reduced
      angiogenesis compared with normal CM (P<0.001), which was not further decreased
      by the addition of exogenous sVEGFR-1, indicating a saturation of the soluble
      receptor. Removal of sVEGFR-1 by immunoprecipitation from preeclamptic CM
      significantly restored migration (P<0.001) and tube formation (P<0.001) to levels
      comparable to that induced by normal CM, demonstrating that elevated levels of
      sVEGFR-1 in preeclampsia are responsible for inhibiting angiogenesis. Our finding
      demonstrates the dysregulation of the VEGF/PlGF axis in preeclampsia and offers
      an entirely new therapeutic approach to its treatment.

PMID- 15472116
TI  - Isolation and expansion of adult cardiac stem cells from human and murine heart.
AB  - Cardiac myocytes have been traditionally regarded as terminally differentiated
      cells that adapt to increased work and compensate for disease exclusively through
      hypertrophy. However, in the past few years, compelling evidence has accumulated
      suggesting that the heart has regenerative potential. Recent studies have even
      surmised the existence of resident cardiac stem cells, endothelial cells
      generating cardiomyocytes by cell contact or extracardiac progenitors for
      cardiomyocytes, but these findings are still controversial. We describe the
      isolation of undifferentiated cells that grow as self-adherent clusters (that we
      have termed "cardiospheres") from subcultures of postnatal atrial or ventricular
      human biopsy specimens and from murine hearts. These cells are clonogenic,
      express stem and endothelial progenitor cell antigens/markers, and appear to have
      the properties of adult cardiac stem cells. They are capable of long-term self
      renewal and can differentiate in vitro and after ectopic (dorsal subcutaneous
      connective tissue) or orthotopic (myocardial infarction) transplantation in SCID
      beige mouse to yield the major specialized cell types of the heart: myocytes (ie,
      cells demonstrating contractile activity and/or showing cardiomyocyte markers)
      and vascular cells (ie, cells with endothelial or smooth muscle markers).

PMID- 15472117
TI  - Binding of myosin binding protein-C to myosin subfragment S2 affects
      contractility independent of a tether mechanism.
AB  - Mutations in the cardiac myosin binding protein-C gene (cMyBP-C) are among the
      most prevalent causes of inherited hypertrophic cardiomyopathy. Although most
      cMyBP-C mutations cause reading frameshifts that are predicted to encode
      truncated peptides, it is not known if or how expression of these peptides causes
      disease. One possibility is that because the N-terminus contains a unique binding
      site for the S2 subfragment of myosin, shortened cMyBP-C peptides could directly
      affect myosin contraction by binding to S2. To test this hypothesis, we compared
      the effects of a C1C2 protein containing the myosin S2 binding site on
      contractile properties in permeabilized myocytes from wild-type and cMyBP-C
      knockout mice. In wild-type myocytes, the C1C2 protein reversibly increased
      myofilament Ca2+ sensitivity of tension, but had no effect on resting tension.
      Identical results were observed in cMyBP-C knockout myocytes where C1C2 increased
      Ca2+ sensitivity of tension with the half-maximal response elicited at
      approximately 5 micromol/L C1C2. Maximum force was not affected by C1C2. However,
      phosphorylation of C1C2 by cAMP-dependent protein kinase reduced its ability to
      increase Ca2+ sensitivity. These results demonstrate that binding of the C1C2
      peptide to S2 alone is sufficient to affect myosin contractile function and
      suggest that regulated binding of cMyBP-C to myosin S2 by phosphorylation
      directly influences myofilament Ca2+ sensitivity.

PMID- 15472118
TI  - Critical role for transient receptor potential channel TRPM4 in myogenic
      constriction of cerebral arteries.
AB  - Local control of cerebral blood flow is regulated in part through myogenic
      constriction of resistance arteries. Although this response requires Ca2+ influx
      via voltage-dependent Ca2+ channels secondary to smooth muscle cell
      depolarization, the mechanisms responsible for alteration of vascular smooth
      muscle (VSM) cell membrane potential are not fully understood. A previous study
      from our laboratory demonstrated a critical role for a member of the transient
      receptor potential (TRP) superfamily of ion channels, TRPC6, in this response.
      Several other of the approximately 22 identified TRP proteins are also present in
      cerebral arteries, but their functions have not been elucidated. Two of these
      channels, TRPM4 and TRPM5, exhibit biophysical properties that are consistent
      with a role for control of membrane potential of excitable cells. We hypothesized
      that TRPM4/TRPM5-dependent currents contribute to myogenic vasoconstriction of
      cerebral arteries. Cation channels with unitary conductance, ion selectivity and
      Ca2+-dependence similar to those of cloned TRPM4 and TRPM5 were present in
      freshly isolated VSM cells. We found that TRPM4 mRNA was detected in both whole
      cerebral arteries and in isolated VSM cells whereas TRPM5 message was absent from
      cerebral artery myocytes. We also found that pressure-induced smooth muscle cell
      depolarization was attenuated in isolated cerebral arteries treated with TRPM4
      antisense oligodeoxynucleotides to downregulate channel subunit expression. In
      agreement with these data, myogenic vasoconstriction of intact cerebral arteries
      administered TRPM4 antisense was attenuated compared with controls, whereas KCl
      induced constriction did not differ between groups. We concluded that activation
      of TRPM4-dependent currents contributed to myogenic vasoconstriction of cerebral
      arteries.

PMID- 15472119
TI  - Epoxycyclopentenone-containing oxidized phospholipids restore endothelial barrier
      function via Cdc42 and Rac.
AB  - After an acute phase of inflammation or injury, restoration of the endothelial
      barrier is important to regain vascular integrity and to prevent edema formation.
      However, little is known about mediators that control restoration of endothelial
      barrier function. We show here that oxidized phospholipids that accumulate at
      sites of inflammation and tissue damage are potent regulators of endothelial
      barrier function. Oxygenated epoxyisoprostane-containing phospholipids, but not
      fragmented oxidized phospholipids, exhibited barrier-protective effects mediated
      by small GTPases Cdc42 and Rac and their cytoskeletal, focal adhesion, and
      adherens junction effector proteins. Oxidized phospholipid-induced cytoskeletal
      rearrangements resulted in a unique peripheral actin rim formation, which was
      mimicked by coexpression of constitutively active Cdc42 and Rac, and abolished by
      coexpression of dominant-negative Rac and Cdc42. Thus, oxidative modification of
      phospholipids during inflammation leads to the formation of novel regulators that
      may be critically involved in restoration of vascular barrier function.

PMID- 15472120
TI  - C-reactive protein enhances LOX-1 expression in human aortic endothelial cells:
      relevance of LOX-1 to C-reactive protein-induced endothelial dysfunction.
AB  - C-reactive protein (CRP), a characteristic inflammatory marker, is a powerful
      predictor of cardiovascular events. Recent data suggest that CRP may also promote
      atherogenesis through inducing endothelial dysfunction. Lectin-like oxidized low
      density lipoprotein (oxLDL) receptor-1 (LOX-1) is a newly identified endothelial
      receptor for oxLDL that plays a pivotal role in oxLDL-induced endothelial
      dysfunction. Whether CRP may regulate endothelial LOX-1 and induce endothelial
      dysfunction through this receptor is unknown. In the present study, we studied
      the in vitro effect of CRP on LOX-1 expression in human aortic endothelial cells
      (HAECs) and the role of LOX-1 in CRP-induced human monocyte adhesion to
      endothelium and oxLDL uptake by endothelial cells. Incubation of HAECs with CRP
      enhanced, in a dose- and time-dependent manner, LOX-1 mRNA and protein levels.
      Induction of LOX-1 protein was already present at 5 microg/mL CRP and reached a
      maximum at 25 microg/mL. This effect was reduced by antibodies against CD32/CD64,
      endothelin-1 (ET-1) and interleukin-6 (IL-6). The extent of stimulation of LOX-1
      achieved by CRP was comparable to that elicited by high glucose and IL-6 and
      remained unchanged in presence of these factors. Finally, CRP increased, through
      LOX-1, both human monocyte adhesion to endothelial cells and oxLDL uptake by
      these cells. We conclude that CRP enhances endothelial LOX-1 expression and
      propose a new mechanism by which CRP may promote endothelial dysfunction, that of
      inducing LOX-1.

PMID- 15472121
TI  - Apurinic/apyrimidinic endonuclease 1 regulates endothelial NO production and
      vascular tone.
AB  - The dual-function protein apurinic/apyrimidinic endonuclease/redox factor-1
      (APE1/ref-1) is essential for DNA repair and also governs the reductive
      activation of many redox-sensitive transcription factors. We examined the role of
      APE1/ref-1 in regulation of endothelium-dependent tone and systemic blood
      pressure. APE1/ref-1+/- mice have impaired endothelium-dependent vasorelaxation,
      reduced vascular NO levels, and are hypertensive. APE1/ref-1 upregulates H-ras
      expression and leads to H-ras-mediated, phosphoinositide-3 kinase/Akt kinase
      dependent calcium sensitization of endothelial NO synthase (eNOS), stimulating NO
      production. The reducing property of APE1/ref-1 is essential for upregulation of
      H-ras and for the calcium sensitization of eNOS. These findings uncover a novel
      physiological role for APE1/ref-1 in regulating vascular tone by governance of
      eNOS activity and bioavailable NO.

PMID- 15472122
TI  - Disruption of autosomal recessive hypercholesterolemia gene shows different
      phenotype in vitro and in vivo.
AB  - We previously characterized the patients with autosomal recessive
      hypercholesterolemia (ARH) as having severe hypercholesterolemia and retarded
      plasma low-density lipoprotein (LDL) clearance despite normal LDL receptor (LDLR)
      function in their cultured fibroblasts, and we identified a mutation in the ARH
      locus in these patients. ARH protein is an adaptor protein of the LDL and
      reportedly modulates its internalization. We developed ARH knockout mice (ARH-/-)
      to study the function of this protein. Plasma total cholesterol level was higher
      in ARH-/- mice than that in wild-type mice (ARH+/+), being attributed to a 6-fold
      increase of LDL, whereas plasma lipoprotein was normal in the heterozygotes
      (ARH+/-). Clearance of 125I-LDL from plasma was retarded in ARH-/- mice, as much
      as that found in LDLR-/- mice. Fluorescence activity of the intravenously
      injected 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)
      LDL was recovered in the cytosol of the hepatocytes of ARH+/+ mice, but not in
      those of ARH-/- or LDLR-/- mice. Also, less radioactivity was recovered in the
      liver of ARH-/- or LDLR-/- mice when [3H]cholesteryl oleyl ether (CE)-labeled LDL
      was injected. In contrast, uptakes of [3H]CE-labeled LDL, 125I-LDL, and DiI-LDL
      were all normal or slightly subnormal when the ARH-/- hepatocytes were cultured.
      We thus concluded that the function of the hepatic LDLR is impaired in the ARH-/-
      mice in vivo, despite its normal function in vitro. These findings were
      consistent with the observations with the ARH homozygous patients and suggested
      that certain cellular environmental factors modulate the requirement of ARH for
      the LDLR function.

PMID- 15472123
TI  - Potential role of endotoxin as a proinflammatory mediator of atherosclerosis.
AB  - Atherosclerosis is increasingly recognized as a chronic inflammatory disease.
      Although a variety of inflammatory markers (ie, C-reactive protein) have been
      associated with atherosclerosis and its consequences, it is important to identify
      principal mediators of the inflammatory responses. One potentially important
      source of vascular inflammation in atherosclerosis is bacterial endotoxin.
      Mutations in Toll-like receptor 4 (TLR-4), an integral component of the endotoxin
      signaling complex, are fairly common in the Caucasian population and have
      recently been associated with reduced incidence of atherosclerosis and other
      cardiovascular diseases in some studies. Moreover, epidemiological studies
      suggest that endotoxemia at levels as low as 50 pg/mL constitutes a strong risk
      factor for the development of atherosclerosis. Endotoxin concentrations in this
      range may be produced by a variety of common subclinical Gram-negative
      infections. In this article, we outline the main elements of the endotoxin
      signaling receptor complex that initiates proinflammatory signaling
      (lipopolysaccharide binding protein [LBP], CD14, TLR-4, and MD-2) and discuss how
      changes in expression of these molecules may affect proatherogenic responses in
      the vessel wall. We also describe some of the proinflammatory effects of
      endotoxin that may be relevant to atherosclerosis, and discuss how serum
      lipoproteins, especially high-density lipoprotein, may modulate endotoxin-induced
      inflammatory responses. Further, we discuss recent findings suggesting that the
      lipid-lowering statins may have an additional protective role in blocking at
      least some of these proinflammatory signaling pathways. Finally, we discuss
      species diversity with regard to endotoxin signaling that should be considered
      when extrapolating experimental data from animal models to humans.

PMID- 15472124
TI  - Molecular interactions leading to lipoprotein retention and the initiation of
      atherosclerosis.
AB  - Atherosclerosis is distinguished by the accumulation of lipoprotein lipid within
      the arterial wall. An ionic interaction of positively charged regions of
      apolipoprotein (apo) B with matrix proteins, including proteoglycans, collagen,
      and fibronectin, is thought to initiate this process. Proteoglycans are complex
      glycoproteins containing highly negatively charged carbohydrate chains. These
      proteins are abundant in atherosclerosis lesions, and they associate with apoB
      containing lipoproteins. Several specific regions of apoB may mediate this
      process. Other lipoprotein-associated proteins, including apoE and lipases, might
      also participate in this process. In addition, retention may occur via
      lipoprotein association with other matrix molecules or as a consequence of intra
      arterial lipoprotein aggregation.

PMID- 15472125
TI  - Granzyme B induces smooth muscle cell apoptosis in the absence of perforin:
      involvement of extracellular matrix degradation.
AB  - OBJECTIVE: T cell-induced cytotoxicity, of which granzyme B is a key mediator, is
      believed to contribute to the pathogenesis of inflammatory vascular diseases. In
      this report, we investigate the mechanism of granzyme B-induced smooth muscle
      cell (SMC) death. METHODS AND RESULTS: The addition of purified granzyme B alone
      to cultured SMCs caused a significant reduction in cell viability. Chromatin
      condensation, phosphatidylserine externalization, and membrane blebbing were
      observed, indicating that the mechanism of granzyme B-induced SMC death was
      through apoptosis. Activated splenocytes from perforin-knockout mice induced SMC
      death through a granzyme B-mediated pathway. Inhibition of the proteolytic
      activities of caspases and granzyme B prevented granzyme B-induced SMC death,
      whereas attenuation of granzyme B internalization with mannose-6-phosphate (M6P)
      did not. Further, granzyme B induced the cleavage of several SMC extracellular
      proteins, including fibronectin, and reduced focal adhesion kinase
      phosphorylation. CONCLUSIONS: These results indicate that granzyme B can induce
      apoptosis of SMCs in the absence of perforin by cleaving extracellular proteins,
      such as fibronectin.

PMID- 15472126
TI  - Essential role of vascular endothelial growth factor and Flt-1 signals in
      neointimal formation after periadventitial injury.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) is upregulated after
      arterial injury. Its role in the pathogenesis of neointimal formation after
      periadventitial injury, however, has not been addressed. METHODS AND RESULTS:
      Expression of VEGF and its receptors but not that of placental growth factor
      markedly increased with the development of neointimal formation in
      hypercholesterolemic mice after cuff-induced periarterial injury. Transfection
      with the murine soluble Flt-1 (sFlt-1) gene to block VEGF in vivo in mice
      inhibited early inflammation and later neointimal formation. The sFlt-1 gene
      transfer did not affect plasma lipid levels but attenuated increased expression
      of VEGF, Flt-1, Flk-1, monocyte chemoattractant protein-1, and other inflammation
      promoting factors. Mice with Flt-1 kinase deficiency also displayed reduced
      neointimal formation. CONCLUSIONS: Inflammatory changes mediated by VEGF and Flt
      1 signals play an important role in the pathogenesis of neointimal formation
      after cuff-induced periadventitial injury. VEGF might promote neointimal
      formation by acting as a proinflammatory cytokine.

PMID- 15472127
TI  - Helicobacter pylori infection causes persistent platelet activation in vivo
      through enhanced lipid peroxidation.
AB  - OBJECTIVE: We aimed at investigating the relationship between Helicobacter pylori
      infection and in vivo lipid peroxidation and platelet activation, as reflected by
      urinary 8-iso-prostaglandin (PG)F(2alpha) and 11-dehydro-thromboxane (TX)B2,
      respectively, in otherwise healthy dyspeptic subjects. METHODS AND RESULTS: We
      measured urinary 8-iso-PGF2alpha and 11-dehydro-TXB2 excretion in 40 dyspeptic
      subjects with a positive 13C-urea breath test and 38 dyspeptic individuals with a
      negative test. Moreover, we investigated the effects of H pylori eradication on
      prostanoid metabolite excretion in 23 H pylori-positive subjects. We also
      measured prostanoid metabolite excretion before and after selective
      cyclooxygenase-2 inhibition with rofecoxib in 4 H pylori-positive subjects.
      Urinary 8-iso-PGF2alpha and 11-dehydro-TXB2 excretion was significantly higher in
      the H pylori-positive individuals than in controls. A significant direct
      correlation was found between the degree of positivity to the 13C-urea breath
      test and urinary 8-iso-PGF2alpha excretion. The latter was linearly correlated
      with urinary 11-dehydro-TXB2. Successful eradication of H pylori infection led to
      a significant reduction in both 8-iso-PGF(2alpha) and 11-dehydro-TXB2.
      Furthermore, their levels were unaffected after treatment with rofecoxib.
      CONCLUSIONS: Our study provides evidence of enhanced in vivo lipid peroxidation
      and platelet activation in association with H pylori infection and suggests a
      novel mechanism by which an infectious agent could contribute to
      atherothrombosis.

PMID- 15472128
TI  - Overexpression of IL-18 decreases intimal collagen content and promotes a
      vulnerable plaque phenotype in apolipoprotein-E-deficient mice.
AB  - OBJECTIVE: Although IL-18 has been implicated in atherosclerotic lesion
      development, little is known about its role in advanced atherosclerotic plaques.
      This study aims to assess the effect of IL-18 overexpression on the stability of
      preexisting plaques. METHODS AND RESULTS: Atherosclerotic lesions were elicited
      in carotid arteries of apolipoprotein E (apoE)-deficient mice (n=32) by placement
      of a perivascular collar. Overexpression of IL-18 was effected by intravenous
      injection of an adenoviral vector 5 weeks after surgery. Two weeks after
      transduction, lesions were analyzed histologically with regard to plaque
      morphology and composition or by real-time polymerase chain reaction. No
      difference in plaque size was detected between groups. In the Ad.IL-18-treated
      group, 62% of lesions displayed a vulnerable morphology or even intraplaque
      hemorrhage as compared with only 24% in the controls (P=0.037). In agreement, IL
      18 overexpression reduced intimal collagen by 44% (P<0.003) and cap-to-core ratio
      by 41% (P<0.002). Although IL-18 did not affect the expression of collagen
      synthesis-related genes, it was found to enhance the collagenolytic activity of
      vascular smooth muscle cells in vitro, suggesting that the low collagen content
      is attributable to matrix degradation rather than to decreased synthesis.
      CONCLUSIONS: Systemic IL-18 overexpression markedly decreases intimal collagen
      content and cap thickness, leading to a vulnerable plaque morphology.

PMID- 15472129
TI  - Intimal thickness is not associated with wall shear stress patterns in the human
      right coronary artery.
AB  - OBJECTIVE: Low wall shear stress has been implicated in atherogenesis throughout
      the arterial tree, including the right coronary artery (RCA). The objective of
      this study was to determine the level of covariation of intimal thickness and
      wall shear stress in the human RCA. METHODS AND RESULTS: Postmortem histological
      measurements of intimal thickness were compared with wall shear stresses
      calculated from computational flow modeling in 4 human right coronary arteries. A
      statistically significant correlation between intimal thickness and wall shear
      stress was found in only 1 of the 4 arteries studied. CONCLUSIONS: Wall shear
      stress does not appear to be related to intimal thickness in the 4 RCAs studied.

PMID- 15472130
TI  - Quantitative and qualitative differences in proatherogenic NKT cells in
      apolipoprotein E-deficient mice.
AB  - BACKGROUND: Atherosclerosis is a disease marked by lipid accumulation and
      inflammation. Recently, atherosclerosis has gained recognition as an autoimmune
      type syndrome characterized by increased activation of the innate and acquired
      immune systems. Natural killer T (NKT) cells have characteristics of both
      conventional T cells and NK cells and recognize glycolipid antigens presented in
      association with CD1d molecules on antigen-presenting cells. The capacity of NKT
      cells to respond to lipid antigens and modulate innate and acquired immunity
      suggests that they may play a role in atherogenesis. METHODS AND RESULTS: We
      examined the role of NKT cells in atherogenesis and how the atherosclerotic
      environment affects the NKT cell population itself. The data show that CD1d
      deficiency in male apolipoprotein E-deficient (apoE(0)) mice results in reduction
      in atherosclerosis, and treatment of apoE(0) mice with alpha-galactosylceramide,
      a potent and specific NKT cell activator, results in a 2-fold increase in
      atherosclerosis. Interestingly, we demonstrate that alpha-galactosylceramide
      induced interferon-gamma responses and numbers of NKT cells in apoE(0) mice show
      age-dependent qualitative and quantitative differences as compared with age
      matched wild-type mice. CONCLUSIONS: Collectively, these findings reveal that
      hyperlipidemia and atherosclerosis have significant effects on NKT cell responses
      and that these cells are proatherogenic.

PMID- 15472131
TI  - Decorin promotes aortic smooth muscle cell calcification and colocalizes to
      calcified regions in human atherosclerotic lesions.
AB  - OBJECTIVE: Ectopic calcification localized to the intima of atherosclerotic
      plaque is a risk marker for cardiovascular events and increases the risk of
      aortic dissection during angioplasty. A variety of extracellular matrix molecules
      such as collagen type 1, bone sialoprotein, and osteopontin are known to regulate
      the biomineralization of bone and ectopic vascular calcification. In the present
      study, it was investigated whether decorin, a small leucine-rich proteoglycan
      expressed in bone and atherosclerotic plaque, is involved in arterial
      calcification. METHODS AND RESULTS: Calcification was induced in cultured bovine
      aortic smooth muscle cell (BASMC) by the addition of beta-glycerophosphate or
      inorganic phosphate. Northern and Western analysis revealed that decorin
      expression was strongly upregulated in mineralizing BASMC. Furthermore,
      overexpression of decorin using a retroviral expression vector resulted in a 3-
      to 4-fold elevation of calcium deposited on the BASMC monolayer. Increased
      calcification in response to decorin could also be mimicked by adding exogenous
      decorin to the cultures. In addition, human coronary atherosclerotic lesions
      taken from sudden-death patients showed marked colocalization of calcium deposits
      with decorin. CONCLUSIONS: Decorin induces calcification of arterial smooth
      muscle cell cultures and colocalizes to mineral deposition in human
      atherosclerotic plaque, suggesting that decorin functions as promoter of intimal
      calcification.

PMID- 15472132
TI  - Clinical significance of coronary calcification.

PMID- 15472133
TI  - Aortic stiffness does not mediate the relation between pulse pressure and CRP.

PMID- 15472134
TI  - Estrogen and HDL: all that glitters is not gold.

PMID- 15472135
TI  - CRP and risk of coronary heart disease: can exercise training cool down the
      flames?

PMID- 15472136
TI  - Molecular phenotypes of atherosclerosis: fingering the perpetrators.

PMID- 15472137
TI  - Vascular cross-talk: a conversation.

PMID- 15472138
TI  - Synergy between A2B adenosine receptors and hypoxia in activating human lung
      fibroblasts.
AB  - Chronic inflammatory airway diseases, such as asthma, chronic obstructive
      pulmonary disease and pulmonary fibrosis, are associated with subepithelial
      fibroblast activation, myofibroblast hyperplasia, hypoxia, and increase in
      interstitial adenosine concentrations. The goal of this study was to determine
      the effect of adenosine and its receptors on activation of human lung fibroblasts
      under normoxia (21% O2) and hypoxia (5% O2). Under the normoxic condition,
      adenosine and its stable analog, 5'-(N-ethylcarboxamido)-adenosine, via
      activation of A2B adenosine receptors, increased the release of interleukin (IL)
      6 by 14-fold and induced the differentiation of human lung fibroblasts to
      myofibroblasts. This latter effect of 5'-(N-ethylcarboxamido)-adenosine was
      abolished by an IL-6-neutralizing antibody. Hypoxia increased the release of IL-6
      by 2.8-fold, and there was a synergy between hypoxia and activation of A2B
      adenosine receptors to increase the release of IL-6 and to induce differentiation
      of fibroblasts into myofibroblasts. Hypoxia increased the expression of A2B
      adenosine receptors by 3.4-fold. Altogether, these data suggest that hypoxia
      amplifies the effect of adenosine on the release of IL-6 and cell differentiation
      by upregulating the expression of A2B adenosine receptors. Our findings provide a
      novel mechanism whereby adenosine participates in the remodeling process of
      inflammatory lung diseases.

PMID- 15472139
TI  - Protein carbonyl formation in the diaphragm.
AB  - Although protein carbonyl formation is an index of oxidative stress in skeletal
      muscles, the exact proteins, which undergo oxidation in these muscles, remain
      unknown. We used 2D electrophoresis, immunoblotting, and mass spectrometry to
      identify carbonylated proteins in the diaphragm in septic animals. Rats were
      injected with saline (control) or Escherichia coli lipopolysaccharides (LPS) and
      killed after various intervals. Diaphragm protein carbonylation increased
      significantly and peaked 12 h after LPS injection, and it was localized both
      inside muscle fibers and in blood vessels supplying muscle fibers. Aldolase A,
      glyceraldehyde 3-phosphate dehydrogenase, enolase 3beta, mitochondrial and
      cytosolic creatine kinases, alpha-actin, carbonic anyhdrase III, and ubiquinol
      cytochrome c reductase were all carbonylated in septic rat diaphragms. In
      addition, we found significant negative correlations between the intensity of
      carbonylation and creatine kinase and aldolase activities. We conclude that
      glycolysis, ATP production, CO2 hydration, and contractile proteins are targeted
      by oxygen radicals inside the diaphragm during sepsis.

PMID- 15472140
TI  - Editorial I: Tiny wonders of tiny impurities of nitrous oxide during anaesthesia.

PMID- 15472141
TI  - Editorial II: Solid as a ROC.

PMID- 15472142
TI  - Editorial III: Nociceptin/orphanin FQ peptide-receptor system: are we any nearer
      the clinic?

PMID- 15472143
TI  - Perioperative cardiac risk.

PMID- 15472144
TI  - Effect of arousal on hypercapnic ventilatory response needs to be examined.

PMID- 15472145
TI  - Blood loss during repair of craniosynostosis.

PMID- 15472146
TI  - Nausea and vomiting after fast-track cardiac anaesthesia.

PMID- 15472147
TI  - Density of spinal anaesthetic solutions.

PMID- 15472148
TI  - Zebrafish, killifish, neither fish, both fish?

PMID- 15472149
TI  - Vascular aging: molecular modulation of the prostanoid cascade by calorie
      restriction.
AB  - The relevance of prostanoids to inflammation, thrombosis, and cardiovascular
      diseases is well known. The present study attempts to explore age effects on
      prostanoids and their biosynthesis cascade. Results from comparing prostanoid
      levels between young (6 months) and old (24 months) Fischer 344 rats showed rises
      of prostaglandin E2 (PGE2), PGI2, and thromboxane A2 (TXA2) levels in the old
      rats. Correlating evidence showed gene expression up-regulation of several
      prostanoid synthase enzymes in old rat aorta. Further, we found that expression
      of the antioxidant enzyme glutathione peroxidase was raised by age in the aorta,
      while superoxide dismutase and catalase expression showed no significant change
      during aging in the aorta. Moreover, calorie restriction (CR) was found to
      attenuate age-related prostanoid changes by suppressing inflammatory activities.
      In conclusion, the data from this study indicated that age-related increases in
      prostanoids and their biosynthesis might be closely associated with a weakened
      antioxidant capacity.

PMID- 15472150
TI  - The catalase -262C/T promoter polymorphism and aging phenotypes.
AB  - A low level of the central antioxidant enzyme catalase has been suggested to be a
      risk factor for diseases influenced by oxidative stress. In this study, we
      investigated the possible association of the catalase -262C/T polymorphism with
      survival, physical and cognitive functioning, and a number of oxidative stress
      mediated disorders. The study population was 2223 Danish individuals, aged 45-93
      years, drawn from three population-based surveys. The results suggest that the
      catalase -262C/T polymorphism is not associated with either survival, or the
      majority of the age-related phenotypes investigated. However, our data indicate a
      statistical significant association of TT homozygosity with improved physical
      functioning as well as a trend of the T allele conferring an improved general
      cognitive functioning, although these results did not remain significant after
      correcting for multiple testing. The results raise the hypothesis that the
      catalase -262T allele serves as protection against neurodegenerative and physical
      decline, although replication in other studies is warranted for confirmation of
      these findings.

PMID- 15472151
TI  - Malondialdehyde, a lipoperoxidation-derived aldehyde, can bring about secondary
      oxidative damage to proteins.
AB  - Lipoperoxidation-derived aldehydes, for example malondialdehyde (MDA), can damage
      proteins by generating covalent adducts whose accumulation probably participates
      in tissue damage during aging. However, the mechanisms of adduct formation and
      their stability are scarcely known. This article investigates whether oxidative
      steps are involved in the process. As a model of the process, the interaction
      between MDA and bovine serum albumin (BSA) was analyzed. Incubation of BSA with
      MDA resulted in rapid quenching of tryptophan fluorescence and appearance of MDA
      protein adduct fluorescence; transition metal ion traces interfered with the
      latter process. MDA induced generation of peroxides in BSA, which was preventable
      with the antioxidant 2,6,-di-tert-butyl-4-methylphenol (BHT). MDA-exposed BSA
      underwent aggregation, degradation, and BHT-sensitive "gel retardation" effects.
      Phycoerythrin fluorescence disappearance, a marker of damage mediated by reactive
      oxygen species, indicated synergism between MDA and metal ions. The interaction
      between reactive aldehydes and proteins is likely to occur in several steps, some
      of them oxidative in nature, giving rise to advanced lipoperoxidation end
      products, which could participate, with advanced glycation end-products, in the
      generation of tissue damage during aging.

PMID- 15472152
TI  - Age-related RNA decline in adult Drosophila melanogaster.
AB  - We investigated the correlation between age and total RNA levels in long-lived
      and control lines of Drosophila melanogaster. Total RNA was extracted at 10 ages
      from 1-63 days posteclosion from 3 inbred lines, with replication. Three
      different methods of RNA quantitation gave highly correlated estimates. Total RNA
      declined substantially with age, exhibiting a dramatic drop in the first few days
      of adult life. We find no evidence for a causal relationship between adult
      longevity and total RNA levels, since long-lived and control lines exhibited
      similar patterns of age-related RNA decline. These observations suggest that the
      dramatic decline in total RNA that occurs early in adult life does not explain
      the twofold differences in life span between lines. The pattern of age-specific
      decline coincides with published observations on age-specific metabolic rates,
      and suggests that 14-day-old flies are functionally senescent.

PMID- 15472153
TI  - Caloric restriction, metabolic rate, and entropy.
AB  - Caloric restriction increases life span in many types of animals. This article
      proposes a mechanism for this effect based on the hypothesis that metabolic
      stability, the capacity of an organism to maintain steady state values of redox
      couples, is a prime determinant of longevity. We integrate the stability
      longevity hypothesis with a molecular model of metabolic activity (quantum
      metabolism), and an entropic theory of evolutionary change (directionality
      theory), to propose a proximate mechanism and an evolutionary rationale for
      aging. The mechanistic features of the new theory of aging are invoked to predict
      that caloric restriction extends life span by increasing metabolic stability. The
      evolutionary model is exploited to predict that the large increases in life span
      under caloric restriction observed in rats, a species with early sexual maturity,
      narrow reproductive span and large litter size, and hence low entropy, will not
      hold for primates. We affirm that in the case of humans, a species with late
      sexual maturity, broad reproductive span and small litter size, and hence high
      entropy, the response of life span to caloric restriction will be negligible.

PMID- 15472154
TI  - Zero tolerance for physical restraints: difficult but not impossible.

PMID- 15472155
TI  - Use of restraints in long-term residential care facilities in Hong Kong SAR,
      China: predisposing factors and comparison with other countries.

PMID- 15472156
TI  - Differences in period prevalence of the use of physical restraints in elderly
      inpatients of European hospitals and nursing homes.

PMID- 15472157
TI  - Cytokine-related aging process.

PMID- 15472158
TI  - Does sarcopenia originate in early life? Findings from the Hertfordshire cohort
      study.
AB  - BACKGROUND: Sarcopenia is defined as the loss of skeletal muscle mass and
      strength with aging. Recent epidemiological studies have shown that men and women
      who grew less well in early life have lower muscle strength. Our objective was to
      investigate the relationship between birth weight, infant growth, and the
      development of sarcopenia. METHODS: We studied 730 men and 673 women, of known
      birth weight and weight at 1 year, who were born in Hertfordshire, U.K., between
      1931 and 1939. Participants completed a health questionnaire, and we measured
      their height, weight, and grip strength. Standard deviation scores for birth
      weight, and for infant growth conditional on birth weight, were analyzed in
      relation to grip strength before and after adjustment for adult size. RESULTS:
      Grip strength was most strongly associated with birth weight in men (r = 0.19, p
      < .001) and women (r = 0.16, p < .001). These relationships remained significant
      after adjustment for adult height and weight. In contrast, the associations with
      infant growth were weakened after allowing for adult size. Adjustment for age,
      current social class, physical activity, smoking, and alcohol did not affect
      these results. CONCLUSIONS: Birth weight is associated with sarcopenia in men and
      women, independently of adult height and weight. The influence of infant growth
      on long-term muscle strength appears to be mediated through adult size.
      Sarcopenia may have its origins in early life, and identifying influences
      operating across the whole life course may yield considerable advances in
      developing effective interventions.

PMID- 15472159
TI  - Adipocytokines, fat distribution, and insulin resistance in elderly men and
      women.
AB  - BACKGROUND: The aim of this study was to evaluate the relation between
      adiponectin and leptin, fat distribution, and insulin resistance in elderly men
      and women. METHODS: 68 elderly participants (28 men and 40 women) aged 66-77
      years, with body mass index (BMI) ranging from 19.83 to 37.18 kg/m2, participated
      in the study. In all participants, we evaluated BMI, waist and hip
      circumferences, sagittal abdominal diameter (SAD), fat mass (FM) by dual energy X
      ray absorptiometry, fasting and 2-hour glucose, insulin, homeostasis model
      assessment of insulin resistance (HOMA), leptin, and adiponectin. RESULTS:
      Elderly women had significantly higher circulating levels of adiponectin and
      leptin compared to men even after adjusting for age, FM, or waist circumference.
      In men and women, leptin was positively associated, whereas adiponectin was
      negatively associated, with BMI, indices of body fat distribution, as well as FM
      and FM%. Both fasting insulin and HOMA showed significant positive correlation
      with leptin and negative correlation with adiponectin in both sexes. In a step
      wise multiple regression model with HOMA as the dependent variable and age,
      gender, waist circumference, FM, leptin, and adiponectin as independent
      variables, waist entered the regression first, explaining 19.7% of HOMA variance,
      leptin was second, and adiponectin was third, explaining each one an additional
      10% of variance. In a multiple linear regression analysis, leptin and adiponectin
      alone explained up to 38% of HOMA variance. CONCLUSION: Leptin and adiponectin
      together seem to be strictly related to insulin resistance in elderly people,
      independently of body fat and body fat distribution.

PMID- 15472160
TI  - Environmental influences on cognitive and brain plasticity during aging.
AB  - In the current article, we provide a critical review of the extant literature
      that has focused on environmental influences on cognitive and brain plasticity
      over the adult life span. The review includes both human epidemiological, and
      human and nonhuman cross-sectional and longitudinal research. We review a number
      of factors that have been suggested to reduce age-related cognitive decline
      including both formal and informal education, leisure pursuits, intellectual
      engagement, and expertise in different skill domains. We also examine the
      literature on cognitive and physical fitness training. We conclude with a
      discussion of the gaps in the literature and suggestions for future research.

PMID- 15472161
TI  - Predictors of adherence with the recommended use of hip protectors.
AB  - BACKGROUND: Hip protectors can prevent many hip fractures in older persons at
      high risk for falling. Few published studies have investigated the use of hip
      protectors in community-dwelling older persons, and the level of adherence with
      their use, and predictors of adherence in this setting, are not clear. The aim of
      this study was to report the predictors of adherence and the level of adherence
      with the use of hip protectors in frail community-dwelling older women. METHODS:
      This cohort study of the intervention group of a randomized, controlled trial
      recruited participants from aged care health services in urban areas of northern
      Sydney, Australia. Participants were 302 women who were 74 years or older (mean
      age, 83 years) and who had 2 or more falls or 1 fall requiring hospital admission
      in the previous year and who lived in their own homes. The main outcome measure
      was adherence with the use of hip protectors. RESULTS: Adherence was
      approximately 53% during the 2 years of the study, and hip protectors were worn
      at the time of 51% of falls. The significant independent predictors of
      nonadherence with hip protector use were lower self-efficacy for hip protector
      use (odds ratio [OR], 0.51; 95% confidence interval [CI],.33 to.79), higher
      number of perceived barriers to hip protector use (OR, 0.52; 95% CI, .38 to.72),
      and lower self-rated health (OR, 0.71; 95% CI, .55 to.93). CONCLUSIONS: Three
      easily measured factors independently predicted subsequent adherence with hip
      protector use. These findings may form the basis for strategies to improve
      adherence with the use of hip protectors and with other types of treatment or
      preventive strategies in older persons.

PMID- 15472162
TI  - Old or frail: what tells us more?
AB  - BACKGROUND: Selecting elderly persons who need geriatric interventions and making
      accurate treatment decisions are recurring challenges in geriatrics.
      Chronological age, although often used, does not seem to be the best selection
      criterion. Instead, the concept of frailty, which indicates several concurrent
      losses in resources, can be used. METHODS: The predictive values of chronological
      age and frailty were investigated in a large community sample of persons aged 65
      years and older, randomly drawn from the register of six municipalities in the
      northern regions of the Netherlands (45% of the original addressees). The
      participants' generative capacity to sustain well-being (i.e., self-management
      abilities) was used as the main outcome measure. RESULTS: When using
      chronological age instead of frailty, both too many and too few persons were
      selected. Furthermore, frailty related more strongly (with beta values ranging
      from -.25 to -.39) to a decline in the participants' self-management abilities
      than did chronological age (with beta values ranging from -.06 to -.14).
      Chronological age added very little to the explained variances of all outcomes
      once frailty was included. CONCLUSIONS: Using frailty as the criterion to select
      older persons at risk for interventions may be better than selecting persons
      based only on their chronological age.

PMID- 15472163
TI  - Individualized feeding assistance care for nursing home residents: staffing
      requirements to implement two interventions.
AB  - BACKGROUND: Recommendations have been made to increase the number of nursing home
      (NH) staff available to provide feeding assistance during meals and to
      individualize care for residents. However, there are few data reflecting the
      number of residents responsive to feeding assistance during meals and what
      alternative interventions might be appropriate for other residents. The purpose
      of this study was to evaluate the effects and staffing requirements of two
      individualized feeding assistance interventions to improve oral food and fluid
      intake in NH residents. METHODS: Skilled nursing participants (n = 134) in 3 NHs
      received a 2-day trial of one-on-one feeding assistance during 6 meals. 68
      participants who did not increase their oral intake in response to feeding
      assistance during meals received a 2-day intervention trial during which snacks
      were offered between meals 3 times daily. As part of both interventions, research
      staff provided adequate feeding assistance that enhanced the resident's self
      feeding ability, social stimulation throughout the meal or snack period, and
      availability of choices for foods and fluids. RESULTS: 46% significantly
      increased their oral intake in response to one-on-one mealtime feeding
      assistance, and the staff time required to implement this intervention was 35 (+/
      8) minutes/meal per resident compared with usual NH care, which averaged 6 (+/-
      9) minutes. 44% of the participants significantly increased their oral intake in
      response to the between-meal snack intervention, which required 12 (+/- 6)
      minutes of staff time per snack/resident compared with usual NH care (1 +/- 4
      minutes). CONCLUSIONS: Most participants (90%) significantly increased their
      daily oral food and fluid intake in response to one of two individualized
      interventions. The staff time necessary to implement each intervention was
      significantly greater than the staff time currently being spent on feeding
      assistance care delivery. Suggestions are made to increase the efficiency of
      staff time when delivering feeding assistance.

PMID- 15472164
TI  - Clinical review 171: The rationale, efficacy and safety of androgen therapy in
      older men: future research and current practice recommendations.
AB  - Epidemiological studies indicate that normal male aging is associated with a
      gradual and variable decline in blood testosterone concentrations and unfavorable
      changes in muscle, bone, and fat that mimic those of androgen deficiency in young
      men. These age-related reductions in muscle and bone mass and increased fat mass
      may be responsible for other age-related changes, including decreased muscle
      strength and physical function, changes in metabolic function, and increased
      falls, fractures, and disability. Whether age-related relative androgen
      deficiency truly causes any of these features requires interventional studies
      specifically in older men, because aged tissues may not remain androgen sensitive
      nor is such treatment necessarily safe. A Medline search (years 1966 through
      January 2004, using search terms random and androgen), supplemented by subsequent
      reference searches of retrieved articles, identified randomized placebo
      controlled studies of androgen therapy. These studies show that androgen
      replacement in older men increases muscle and reduces fat mass to a small degree,
      but to date has not improved muscle strength, physical function, or insulin
      sensitivity, nor does it convincingly improve bone density, although the latter
      effect is particularly dose responsive. However, idiosyncratic adverse effects,
      such as disordered sleep and breathing as well as polycythemia, are also dose
      responsive, suggesting that dose escalation to increase efficacy may create or
      aggravate undesirable side effects. Furthermore, the clinical safety of androgen
      therapy for cardiovascular and prostatic disease is uncertain. Under these
      circumstances, androgen supplementation is not recommended in healthy older men.
      However, interim recommendations are available to help guide appropriate and curb
      unnecessary androgen prescription for symptomatic older men with low serum
      testosterone levels.

PMID- 15472165
TI  - Editorial: Metformin--comparison with other therapies in ovulation induction in
      polycystic ovary syndrome.

PMID- 15472166
TI  - Metformin administration versus laparoscopic ovarian diathermy in clomiphene
      citrate-resistant women with polycystic ovary syndrome: a prospective parallel
      randomized double-blind placebo-controlled trial.
AB  - At present, it is unclear what the role is of laparoscopic ovarian diathermy
      (LOD) and of metformin administration as second-line treatments for ovulation
      induction in women with polycystic ovary syndrome (PCOS) after failure of
      clomiphene citrate (CC) treatment. The aim of the present study was to compare in
      a randomized double-blind placebo-controlled fashion the effectiveness of LOD
      with metformin administration in the treatment of CC-resistant women with PCOS. A
      total of 120 overweight primary infertile anovulatory CC-resistant women with
      PCOS were enrolled and randomized into two groups of treatment. Group A underwent
      diagnostic laparoscopy, whereas group B underwent LOD. At hospital discharge, the
      patients were treated for 6 months with metformin cloridrate (group A; 850 mg
      twice daily) or with multivitamins (group B). The ovulation, pregnancy, abortion,
      and live-birth rates were evaluated. At the end of the study, the total ovulation
      rate was not statistically different between both treatment groups (54.8 vs.
      53.2% [correction] in groups A and B, respectively), whereas the pregnancy (21.8
      [correction] vs. 13.4%), the abortion (9.3 [correction] vs. 29.0%), and the live
      birth (86.0 [correction] vs. 64.5%) rates were significantly (P < 0.05) different
      between the two groups. Our data show that metformin administration is more
      effective than LOD in overall reproductive outcomes in overweight infertile CC
      resistant women with PCOS.

PMID- 15472167
TI  - A new germline RET mutation apparently devoid of transforming activity
      serendipitously discovered in a patient with atrophic autoimmune thyroiditis and
      primary ovarian failure.
AB  - Gain-of-function RET mutations are responsible for multiple endocrine neoplasia
      syndromes (MEN) 2A and 2B and familial medullary thyroid carcinoma (FMTC),
      whereas loss-of-function mutations are found in Hirschsprung disease. We report a
      new RET point mutation [R694Q (CGG-->CAG)], serendipitously found in a 23-yr-old
      woman with hypothyroidism due to atrophic Hashimoto's thyroiditis and primary
      ovarian failure, without altered calcitonin secretion. Familial history and
      clinical and biochemical evaluation of first-degree relatives were negative for
      FMTC, MEN 2A and 2B, and Hirschsprung disease. Genetic analysis showed that the
      mutation was inherited from the mother, who was submitted 2 yr before to
      thyroidectomy for goitrous Hashimoto's thyroiditis. Histological revision and
      immunohistochemical studies documented normal C cell number and morphology. We
      cloned the mutation in an expression vector encoding a full-length RET protein.
      The construct was transiently expressed in 293T cells in parallel with a wild
      type RET and a C634R MEN 2A-associated RET mutant. Proteins were harvested from
      transfected cells, and tyrosine phosphorylation levels were assayed. The mutation
      did not exert significant potentiating effects on RET kinase. A focus assay was
      also performed on NIH3T3 fibroblasts; the mutant did not exert significant
      transforming activity. In conclusion, a new RET mutation was found in two
      subjects without any evidence of MEN and FMTC. In keeping with clinical data,
      transfection studies confirmed lack of activating activity. This serendipitous
      discovery, apparently devoid of oncogenic potential, underscores the problems
      that may be encountered in genomic studies on RET.

PMID- 15472168
TI  - A case of chromosome 22q11 deletion syndrome diagnosed in a 32-year-old man with
      hypoparathyroidism.
AB  - Congenital hypoparathyroidism typically manifests with hypocalcemia with or
      without associated characteristic physical findings and is usually diagnosed
      during the neonatal period. This report describes an African-American male who
      was diagnosed at age 32 yr to have dysgenesis of the parathyroid glands due to
      chromosome 22 microdeletion. Symptomatic hypocalcemia did not develop until age
      14 yr, a few weeks after initiation of anticonvulsant therapy for generalized
      tonic-clonic seizures. Because of the timing for onset of symptomatic
      hypocalcemia, it was presumed that the patient had anticonvulsant-induced
      hypocalcemia, and he carried that diagnosis for 18 yr. Chromosome 22q11 deletion
      syndrome was first suspected at age 32 yr, based on the findings of subtle
      dysmorphic facial features and a history of learning disability in a patient with
      PTH-deficient hypocalcemia. The diagnosis was confirmed by fluorescence in situ
      hybridization analysis. This case underscores the variable clinical presentation
      of this congenital form of hypoparathyroidism. Chromosome 22q11 microdeletions
      are relatively common, and the diagnosis should be considered even in adults with
      hypoparathyroidism because of the potential benefit of genetic counseling.

PMID- 15472169
TI  - Congenital leptin deficiency due to homozygosity for the Delta133G mutation:
      report of another case and evaluation of response to four years of leptin
      therapy.
AB  - Congenital leptin deficiency is a rare, but treatable, cause of severe early
      onset obesity. To date, two United Kingdom families of Pakistani origin carrying
      a frameshift/premature stop mutation, c.398delG (Delta133G), and one Turkish
      family carrying a missense mutation, c.313C>T (Arg(105)Trp), have been described.
      Affected subjects are homozygotes and manifest severe obesity and hyperphagia
      accompanied by metabolic, neuroendocrine, and immune dysfunction. The effects of
      recombinant leptin therapy have been reported in three children with the
      Delta133G mutation, and in all cases this has led to a dramatic resolution of
      clinical and biochemical abnormalities. We now report a Canadian child, of
      Pakistani origin but unrelated to the previously reported subjects, presenting
      with severe hyperphagia and obesity, who was found to be homozygous for the
      Delta133G mutation. In this child, 4 yr of therapy with sc injections of
      recombinant leptin provided additional evidence for the sustained beneficial
      effects of leptin replacement on fat mass, hyperinsulinemia, and hyperlipidemia.
      In addition, leptin administration corrected abnormal thyroid biochemistry and
      allowed the withdrawal of T(4) treatment, providing additional support for the
      role of leptin in the regulation of the human hypothalamic-pituitary-thyroid
      axis.

PMID- 15472170
TI  - Erlenmeyer flask.

PMID- 15472171
TI  - Gonadal dysgenesis without adrenal insufficiency in a 46, XY patient heterozygous
      for the nonsense C16X mutation: a case of SF1 haploinsufficiency.
AB  - Targeted disruption of the orphan nuclear receptor SF1 results in the absence of
      adrenals and gonads, establishing that this transcription factor is implicated in
      gonadal determination and adrenal development. Four human SF1 gene mutations have
      been described to date: three (G35E, R92Q, R255L) were responsible for adrenal
      insufficiency associated with a gonadal dysgenesis in two 46, XY individuals, one
      (8 bp deletion in exon 6) resulted in gonadal dysgenesis without adrenal
      insufficiency. We identified a new heterozygous SF1 gene mutation, C16X, in a 46,
      XY patient showing gonadal dysgenesis with normal adrenal function: low basal
      levels of AMH and testosterone (T), weak T response to hCG, hypoplastic testes
      with abundant seminiferous tubules but rare germ cells. This mutation causes
      premature termination of translation and should abolish all SF1 activity.
      Therefore haploinsufficiency could explain the deleterious effect of this
      mutation in our patient suggesting that testis development is more SF1 dose
      dependent than adrenal development. Although the same mechanism explains the
      deleterious effects of SF1 missense mutations, recent studies have demonstrated
      an additional dominant negative effect. These data suggest that heterozygous
      mutation impaired adrenal development only if the two mechanisms, gene dosage and
      dominant negative effects occur.

PMID- 15472172
TI  - Somatostatin is expressed and secreted by human adipose tissue upon infection and
      inflammation.
AB  - Somatostatin (SRIF) is a well-known neuroendocrine secretion product. SRIF
      expression and secretion are induced after inflammation in murine macrophages and
      in endotoxin-injected sheep and pigs. Because adipocytes have been demonstrated
      to produce numerous cytokines and peptide hormones, we investigated the
      expression of SRIF and its receptors (SSTR1-5) in human adipose tissue after
      inflammatory stimulation in vitro and in tissues from patients with septic
      disease.Preadipocyte-derived adipocytes, mesenchymal stem cell-derived
      adipocytes, and mature explanted adipocytes expressed SRIF-mRNA after endotoxin
      [lipopolysaccharide (LPS)] or IL-1beta treatments. LPS- and IL-1beta-mediated
      SRIF-mRNA induction was blocked by pretreatment with dexamethasone. Using
      cocultures and quantitative real-time PCR, we demonstrate adipocyte SRIF
      induction by secretion factors from activated peripheral blood mononuclear cell
      derived macrophages. In contrast to basal adipocytes, SRIF protein was detected
      in culture supernatants of LPS-treated and of combined TNFalpha/IL-1beta/LPS
      treated adipocytes. SRIF protein was visualized by immunohistochemistry in
      explanted minced adipose tissue after overnight incubation in culture medium
      supplemented with combined IL-1beta and LPS. In septic patients, expression of
      SRIF-mRNA and SRIF protein was found in visceral, but not in sc, adipose tissue.
      Adipocyte mRNA abundance of SSTR 1-5 was differentially regulated by inflammatory
      treatments.Thus, human visceral adipose tissue secretes SRIF during inflammation
      and sepsis and expresses several SSTRs. It is tempting to speculate that visceral
      adipose tissue-derived SRIF plays a modulatory role in the immunological and
      metabolic response to inflammation.

PMID- 15472173
TI  - Parathyroid hormone gene polymorphism and sporadic idiopathic hypoparathyroidism.
AB  - The pathogenetic mechanisms involved in the development of sporadic idiopathic
      hypoparathyroidism are currently under investigation. Although autoantibodies
      against the calcium-sensing receptor (CaSR) have been implicated to play a role,
      these could be demonstrated in only 49% of a group of 51 patients with sporadic
      idiopathic hypoparathyroidism that we previously studied. Therefore, we
      investigated 49 of these patients further, regardless of their antibody status,
      and looked for mutations in the section of the PTH gene sequence that coded for
      prepro-PTH as well as the 3'-untranslated region (3'-UTR) of the gene, which is
      believed to be involved in the stability of its mRNA. We also examined the
      relationship between the clinical manifestations of the disease and the
      occurrences of two commonly observed single nucleotide polymorphisms (SNPs) in
      the PTH gene. In 49 of the patients with idiopathic hypoparathyroidism and in 55
      healthy controls, the SNPs were characterized by restriction analysis using DraII
      and BstBI enzymes. In a subset of these patients, exons 2 and 3 of the PTH gene
      (n = 37) and its 3'-UTR region (n = 40) were also sequenced. No mutations were
      observed in the segment of the PTH gene coding for the signal peptide,
      prohormone, or the 3'-UTR region. However, three well described SNPs were
      observed: 1) an A-->G substitution in intron 1 in 35.1% of the patients; 2) a G-
      >A substitution in intron 2, characterized by BstBI, in one or both alleles in
      27%; and 3) a C-->A substitution at codon 52 (CGA) of exon 3, characterized by
      DraII, in one or both alleles in 59.7% of the patients. There was no significant
      difference in the frequency of occurrence of these SNPs between the patient and
      the control groups. Furthermore, the mean age at onset of symptoms, body mass
      index, frequency of cataract, tetany, convulsion, basal ganglia calcification,
      serum calcium, inorganic phosphorus, and intact PTH were not significantly
      different between patients with and without the above-described SNPs. Thus, the
      data from this report demonstrate that in patients with sporadic idiopathic
      hypoparathyroidism, neither the clinical manifestations nor the biochemical
      indexes of the disease are related to the occurrence of mutations or SNPs in the
      PTH gene. Because neither patient nor control samples exhibited any variations in
      the sequence of their 3'-UTR regions, it is unlikely that mRNA instability is a
      factor in the pathogenesis of the disease. Additional studies are required to
      investigate the role of other genes and autoantigens that may be involved in the
      genesis of idiopathic hypoparathyroidism.

PMID- 15472174
TI  - An insertional polymorphism of the proopiomelanocortin gene is associated with
      fasting insulin levels in childhood obesity.
AB  - Lines of evidence show a role of the melanocortinergic system in the regulation
      of glucose metabolism in obese subjects. The aim of this study was to investigate
      the influence of proopiomelanocortin (POMC) in the variability of insulin levels
      in early-onset obesity. To address this issue, an association study using a 9-bp
      insertional polymorphism, AGC AGC GGC, between nucleotides 6979 and 6998 of the
      POMC gene, was performed in 380 (185 girls) Italian obese children and
      adolescents. Allelic frequencies were comparable in our patients (0.053) and in
      300 lean controls of Mediterranean descent (0.045). Interestingly, we showed that
      this polymorphism, in the obese patients, was associated with differences in
      fasting insulin levels; this finding persisted after correction for age, sex, and
      pubertal stage. Heterozygotes had 24% higher mean insulin levels than those
      homozygous for the wild allele and showed a stronger correlation between insulin
      and body mass index (P < 0.001). These findings support the hypothesis that the
      melanocortin pathway may modulate glucose metabolism in obese subjects and
      suggest that this common POMC variant may be involved in the natural history of
      polygenic obesity in late adolescence and adulthood, contributing to the link
      between type 2 diabetes and obesity.

PMID- 15472175
TI  - Long-term growth hormone therapy in adulthood results in significant linear
      growth in siblings with a PROP-1 gene mutation.
AB  - PROP-1 gene mutations result in impaired production of GH, gonadotropins, TSH,
      and prolactin. We describe three adult siblings, aged 18-25 yr, with short
      stature, hypothyroidism, and lack of pubertal maturation, who were homozygous for
      301-302delAG PROP-1 mutation. We had the unique opportunity to treat them in
      adulthood with GH for 4-5 yr and thyroid replacement before sex steroid
      replacement. Sibling 1, a female, had a chronological age (CA) of 25 yr 8 months,
      a bone age (BA) of 12.5 yr, and height of 128.7 cm [-5.29 sd score (SDS)];
      sibling 2, a younger sister had a CA of 22 yr 5 months, a BA of 13 yr, and height
      of 137.5 cm (-3.94 SDS); and sibling 3, a male, had a CA of 18 yr 4 months, a BA
      of 11.5 yr, and height of 127.5 cm (-6.38 SDS). Despite delay in treatment and
      fairly advanced BA, all responded to GH and thyroid hormone therapy with a
      dramatic increase in linear growth: 22.3 cm for sibling 1, 22 cm for sibling 2,
      and 34.5 cm for sibling 3. After sex hormone replacement, siblings 1, 2, and 3
      grew another 2.6, 3, and 9.5 cm to final heights of 153.6, 162.5, and 171.5 cm,
      respectively. In conclusion, the substantial linear growth in adult siblings with
      a PROP-1 mutation illustrates that despite an advanced BA, linear growth
      potential remains in adulthood in the setting of sex steroid deficiency.

PMID- 15472176
TI  - Continued growth hormone (GH) treatment after final height is necessary to
      complete somatic development in childhood-onset GH-deficient patients.
AB  - Lean body mass (LBM), fat mass (FM), and total bone mineral content are
      significantly reduced in adult GHD subjects who had received pediatric GH. To
      test the hypothesis that continued GH therapy after final height is necessary to
      attain adult body composition, we performed a prospective, multinational,
      randomized, controlled, 2-yr study in patients who completed pediatric GH
      treatment at final height. Patients were randomized to GH at 25.0 microg/kg x d
      (pediatric dose; n = 58) or 12.5 microg/kg x d (adult dose; n = 59) or no GH
      treatment (control; n = 32). LBM and FM were measured by dual energy x-ray
      absorptiometry and were centrally evaluated. IGF-I, IGF-binding protein-3, and
      lipid concentrations were also measured centrally. During the 2 yr, GH-treated
      patients gained a significant amount of LBM compared with controls (P < 0.001),
      but the change with the higher pediatric dose (14.2 +/- 11.7%) was not different
      from that seen with the lower adult dose (12.7 +/- 9.4%; P = 0.970). Similarly,
      the decrease in FM was significantly (P = 0.029) influenced by treatment, but
      with no dose effect (adult dose, -7.1 +/- 22.8%; pediatric dose, -6.0 +/- 26.6%;
      P = 0.950). When the GH treatment effect was analyzed by gender, males gained
      15.6 +/- 9.8% and 14.3 +/- 11.7% LBM (P = 0.711) and lost 12.4 +/- 22.2% and 11.0
      +/- 27.1% FM (P = 0.921) with the low and high doses, respectively. Females
      gained 8.3 +/- 7.3% and 12.5 +/- 12.8% LBM with the two doses (P = 0.630), but
      increased their FM by 3.5 +/- 16.2% with the lower dose and lost only 1.2 +/-
      23.2% FM with the higher dose (P = 0.325). A similar pattern was seen in IGF-I sd
      score; the 2-yr GH dose response was significantly higher with the pediatric than
      with the adult dose in females (P = 0.008), but not males (P = 0.790). The
      divergent pattern of change in LBM and FM in males and females is consistent with
      normal developmental sexual dimorphism and indicates that GH-dependent progress
      to target body composition continues after the age at which GH treatment is
      usually terminated. Dose requirements may have to be adjusted by gender, with
      females requiring a higher dose than males.

PMID- 15472177
TI  - Effects of androgen therapy on adipose tissue and metabolism in older men.
AB  - We investigated the effects of oxandrolone on regional fat compartments and
      markers of metabolism. Thirty-two 60- to 87-yr-old men (body mass index, 28.1 +/-
      3.4 kg/m(2)) were randomized to oxandrolone (20 mg/d; n = 20) or matching placebo
      (n = 12) treatment for 12 wk. Oxandrolone reduced total (-1.8 +/- 1.0 kg; P <
      0.001), trunk (-1.2 +/- 0.6 kg; P < 0.001), and appendicular (-0.6 +/- 0.6 kg; P
      < 0.001) fat, as determined by dual energy x-ray absorptiometry. The changes in
      total and trunk fat were greater (P < 0.001) than the changes with placebo. By
      magnetic resonance imaging, visceral adipose tissue decreased (-20.9 +/- 12
      cm(2); P < 0.001), abdominal sc adipose tissue (SAT) declined (-10.7 +/- 12.1
      cm(2); P = 0.043), the ratio VAT/SAT declined from 0.57 +/- 0.23 to 0.49 +/- 0.19
      (P = 0.002), and proximal and distal thigh SC fat declined [-8.3 +/- 6.7 cm(2) (P
      < 0.001) and -2.2 +/- 3.0 kg (P = 0.004), respectively]. Changes in proximal and
      distal thigh SC fat with oxandrolone were different than with placebo (P = 0.018
      and P = 0.059). A marker of insulin sensitivity (quantitative insulin sensitivity
      check index) improved with oxandrolone by 0.0041 +/- 0.0071 (P = 0.018) at study
      wk 12. Changes in total fat, abdominal SAT, and proximal extremity SC fat were
      correlated with changes in fasting insulin from baseline to study wk 12 (r >or=
      0.45; P < 0.05). Losses of total fat and SAT were greater in men with baseline
      testosterone of 10.4 nmol/liter or less (<or= 300 ng/dl) than in those with
      higher levels [-2.5 +/- 1.1 vs. -1.5 +/- 0.8 kg (P = 0.036) and -24.1 +/- 14.3
      vs. -2.9 +/- 21.3 cm(2) (P = 0.03), respectively]. Twelve weeks after
      discontinuing oxandrolone, 83% of the reductions in total, trunk, and extremity
      fat by dual energy x-ray absorptiometry scanning were sustained (P < 0.02).
      Androgen therapy, therefore, produced significant and durable reductions in
      regional abdominal and peripheral adipose tissue that were associated with
      improvements in estimates of insulin sensitivity. However, high-density
      lipoprotein cholesterol decreased by -0.49 +/- 0.21 mmol/liter and directly
      measured low-density lipoprotein cholesterol increased by 0.57 +/- 0.67
      mmol/liter and non-high-density lipoprotein cholesterol increased by 0.54 +/-
      0.97 mmol/liter (P < 0.03 for each) during treatment with oxandrolone; these
      changes were largely reversible. Thus, therapy with an androgen that does not
      adversely affect lipids may be beneficial for some components of the metabolic
      syndrome in overweight older men with low testosterone levels.

PMID- 15472178
TI  - Psychological adaptation in children with idiopathic short stature treated with
      growth hormone or placebo.
AB  - The influence of short stature on psychological adaptation in childhood and
      adolescence is controversial. GH is currently used to treat children with
      idiopathic short stature (ISS, also known as non-GH-deficient short stature).
      This study represents the first double-blind, placebo-controlled trial of the
      effects of GH on the psychological adaptation of children and adolescents with
      ISS, treated with GH until adult height was attained.Sixty-eight children (53
      males, 15 females), 9-16 yr old, with marked ISS (measured height or predicted
      adult height -2.5 sd or less) received either GH 0.074 mg/kg or placebo sc three
      times per week until height velocity decreased to less than 1.5 cm/yr. Parents
      completed the Child Behavior Checklist (CBCL) and children the Self-Perception
      Profile (SPP) and Silhouette Apperception Technique at baseline and annually
      thereafter. Baseline behavioral/emotional adjustment (CBCL) and self-concept
      (SPP) scores for children with ISS were within the normative range. The two study
      groups exhibited similar behavioral and self-concept profiles (CBCL) during the
      first 2 yr of the study. However, CBCL behavior problems (internalizing,
      externalizing, and total problems) appeared to decline, in yr 3 and 4, in the GH
      treated group relative to the placebo-treated group. Group differences in CBCL
      competency domains and the SPP were not observed at any point during the study.
      Short stature among children with ISS enrolled in this long-term, placebo
      controlled study was not associated with problems in psychological adaptation or
      self-concept with the psychological instruments employed. GH treatment was
      associated with a trend toward improvement in problem behaviors, as measured by
      questionnaires (CBCL) completed by study participants' parents. It remains to be
      determined whether GH treatment significantly impacts adaptation, psychosocial
      function, or quality of life in children with ISS.

PMID- 15472179
TI  - Prevention of postmenopausal bone loss: six-year results from the Early
      Postmenopausal Intervention Cohort Study.
AB  - We report the effect of continuous treatment with alendronate for 6 yr vs.
      placebo in the Early Postmenopausal Intervention Cohort study. A total of 1609
      healthy, early postmenopausal women were recruited; we describe results for the
      585 women who received continuous placebo or alendronate (2.5 or 5 mg) daily for
      6 yr. Bone mineral density (BMD) was evaluated at the lumbar spine, hip, forearm,
      and total body at baseline and annually thereafter. Bone turnover markers were
      measured every 6 months from baseline to yr 2 and annually thereafter. Adverse
      experiences, including upper gastrointestinal events and fractures, were recorded
      throughout the study. Women receiving placebo experienced progressive decreases
      in BMD at all skeletal sites. Patients receiving alendronate experienced
      significant gains in spine and hip BMD that were maintained through yr 6.
      Significantly greater, dose-related decreases in bone turnover markers in the
      alendronate groups vs. placebo occurred within the first year and were sustained
      through yr 6. Women receiving alendronate had adverse experience incidences
      similar to those receiving placebo. Fractures occurred in 11.5, 10.3, and 8.9% of
      women taking placebo, 2.5 mg alendronate, or 5 mg alendronate daily,
      respectively. Therapy with alendronate is an effective and promising strategy for
      the prevention of postmenopausal osteoporosis.

PMID- 15472180
TI  - Growth hormone therapy and bone mineral density in Turner syndrome.
AB  - In a previous report, preliminary data showed a significant reduction in cortical
      bone mineral density (BMD) in women with Turner syndrome that had been treated
      with GH compared with women with Turner syndrome that had not been treated. To
      clarify this point, we have investigated the effects of GH treatment at multiple
      sites in this case-control, cross-sectional study. There were 23 women per group,
      who were similar in age, height, body mass index, estrogen use, and ethnic
      makeup. Median age (range) at start and duration of GH treatment was 9 (3-17) and
      5 (2-9) yr, respectively. GH-treated women had a slightly greater ( approximately
      8%, P = 0.03) width of the radial shaft, but otherwise there were no significant
      differences between groups in bone dimensions or BMD at the distal radius, lumbar
      spine, or femoral neck. Furthermore, regression analysis in a linear model
      including independent variables of age, age at diagnosis, body mass index,
      presence of spontaneous puberty, and GH use confirmed that GH use did not
      contribute to variation in BMD.

PMID- 15472181
TI  - Spontaneous subclinical hypothyroidism in patients older than 55 years: an
      analysis of natural course and risk factors for the development of overt thyroid
      failure.
AB  - We aimed to analyze the natural course of subclinical hypothyroidism, quantify
      the incidence rate of overt hypothyroidism, and evaluate the risk factors for the
      development of definitive thyroid failure in elderly patients. One hundred seven
      patients (93 women and 14 men) over age 55 yr with subclinical hypothyroidism and
      no previous history of thyroid disease were prospectively studied. Subjects were
      followed up for 6-72 months (mean, 31.7 months) with repeated determinations of
      TSH and free T(4). Twenty-eight patients (26.8%) developed overt hypothyroidism,
      and 40 (37.4%) showed normalization of their TSH values. The incidence rate of
      overt hypothyroidism was 9.91 cases per 100 patient-years in the whole
      population, and 1.76, 19.67, and 73.47 cases per 100 patient-years in subjects
      with initial TSH values between 5.0-9.9, 10.0-14.9, and 15.0-19.9 mU/liter,
      respectively. Kaplan-Meier analysis showed that the development of definitive
      thyroid hypofunction was significantly related to the presence of symptoms of
      hypothyroidism, goiter, positive thyroid antibodies (P < 0.05), and mainly low
      normal free T(4) (P < 0.01) and high TSH (P < 0.0001) concentrations at baseline.
      A stepwise multivariate Cox regression analysis showed that the only significant
      factor for progression to overt hypothyroidism was serum TSH concentration (P <
      0.0001). In conclusion, TSH concentration is the most powerful predictor for the
      outcome of spontaneous subclinical hypothyroidism in patients over age 55 yr.
      Subjects with mildly elevated TSH have a low incidence rate of overt
      hypothyroidism. We recommend follow-up with clinical and biochemical monitoring
      in these patients.

PMID- 15472182
TI  - Polymorphism in the growth hormone gene, weight in infancy, and adult bone mass.
AB  - Epidemiological studies point to the importance of gene-environment interactions
      during early life as determinants of later osteoporosis and fracture. We examined
      associations between common single nucleotide polymorphisms in the human GH (GH1)
      gene and weight in infancy, adult bone mass and bone loss rates, and circulating
      GH profiles. Two hundred and five men and 132 women, aged 61-73 yr, in the
      Hertfordshire Cohort Study were included; bone mineral density was measured by
      dual energy x-ray absorptiometry over 4 yr. Twenty-four-hour circulating GH
      profiles were constructed in a subset of 71 men and women. Genomic DNA was
      examined for two single nucleotide polymorphisms in the GH gene (one in the
      promoter region and one in intron 4). Homozygotes at loci GH1 A5157G and T6331A
      displayed low baseline bone density and accelerated bone loss; there was also a
      significant (P = 0.04) interaction among weight at 1 yr, GH1 genotype, and bone
      loss rate. There was a graded association between alleles and circulating GH
      concentration among men. This study suggests that common diversity in the GH1
      region predisposes to osteoporosis via effects on the level of GH expression. The
      interaction with infant weight suggests that early environment may influence the
      effect of GH1 genotype on bone loss.

PMID- 15472183
TI  - Associations between vitamin K biochemical measures and bone mineral density in
      men and women.
AB  - Few data exist on the association between vitamin K status and bone mineral
      density (BMD) in men and women of varying ages. We examined cross-sectional
      associations between biochemical measures of vitamin K status and BMD at the hip
      and spine in 741 men and 863 women (mean age, 59 yr; range, 32-86 yr) who
      participated in the Framingham Heart Study (1996-2000). Vitamin K status was
      assessed by plasma phylloquinone and percentage undercarboxylated osteocalcin
      (%ucOC). Among the men, low plasma phylloquinone concentrations adjusted for
      triglycerides and elevated serum %ucOC levels were associated with low BMD at the
      femoral neck (P = 0.03 and 0.009, respectively). Among postmenopausal women not
      using estrogen replacements, low plasma phylloquinone concentrations were
      associated with low spine BMD (P = 0.007), with a nonsignificant trend of an
      elevated serum %ucOC with low spine BMD (P = 0.08). In contrast, there were no
      significant associations between biochemical measures of vitamin K and BMD in
      either premenopausal women or postmenopausal women using estrogen replacements.
      Clinical trials are required to isolate any putative effects of vitamin K on
      rates of bone loss. The target population in these trials, particularly in regard
      to estrogen use, may be critical, as suggested by the findings of this study.

PMID- 15472184
TI  - Origins and consequences of the elongation of the human menstrual cycle during
      the menopausal transition: the FREEDOM Study.
AB  - The menopausal transition is characterized by the appearance of elongated cycles,
      which become longer and more frequent as menopause approaches. Several endocrine
      abnormalities have been attributed to these cycles; however, no quantitative
      studies of their causes and consequences exist to date. This study is based on
      sequential daily urinary concentrations of FSH, LH, estrone 3-glucuronide (E1G),
      and pregnanediol 3-glucuronide (PdG) from 34 women with perimenopausal menstrual
      irregularity (total of 289 cycles). The timing of ovarian response was determined
      as the day of E1G take-off (ETO). Other parameters measured were the mean FSH
      concentration before ETO (FSH(ETO)) and the midluteal levels of PdG, E1G, and LH.
      There was a strong parallelism between ETO and cycle length variability. FSH(ETO)
      levels increased gradually with ETO. Both ETO and FSH(ETO) were inversely related
      to luteal PdG and directly related to E1G. PdG and LH levels were inversely
      related. All comparisons were highly significant (P < 0.0001). We conclude that
      delayed ovarian response underlies the elongation of the menstrual cycle in the
      menopausal transition, which is likely to be caused by a temporary lack of
      ovarian responsiveness to FSH. A progressive decline in luteal PdG with increased
      E1G occurs in association with these trends.

PMID- 15472185
TI  - The effect of calcium supplementation on bone density in premenarcheal females: a
      co-twin approach.
AB  - The age and developmental stage at which calcium supplementation produces the
      greatest bone effects remain controversial. We tested the hypothesis that calcium
      supplementation may improve bone accrual in premenarcheal females. Fifty-one
      pairs of premenarcheal female twins (27 monozygotic and 24 dizygotic; mean +/- sd
      age, 10.3 +/- 1.5 yr) participated in a randomized, single-blind, placebo
      controlled trial with one twin of each pair receiving a 1200-mg calcium carbonate
      (Caltrate) supplement. Areal bone mineral density (aBMD) was measured at baseline
      and 6, 12, 18 and 24 months. There were no within-pair differences in height,
      weight, or calcium intake at baseline. Calcium supplementation was associated (P
      < 0.05) with increased aBMD compared with placebo, adjusted for age, height, and
      weight at the following time points from baseline: total hip, 6 months (1.9%), 12
      months (1.6%), and 18 months (2.4%); lumbar spine, 12 months (1.0%); femoral
      neck, 6 months (1.9%). Adjusted total body bone mineral content was higher in the
      calcium group at 6 months (2.0%), 12 months (2.5%), 18 months (4.6%), and 24
      months (3.7%), respectively (all P < 0.001). Calcium supplementation was
      effective in increasing aBMD at regional sites over the first 12-18 months, but
      these gains were not maintained to 24 months.

PMID- 15472186
TI  - Immediate fall of bone formation and transient increase of bone resorption in the
      course of high-dose, short-term glucocorticoid therapy in young patients with
      multiple sclerosis.
AB  - Glucocorticoid (GC)-induced osteoporosis is the leading form of secondary
      osteoporosis. Bone loss can be rapid. However, longitudinal studies at the very
      beginning of treatment are scarce. Patients relapsing from multiple sclerosis are
      treated with high-dose, short-term iv GCs. A number of them are young, without
      concomitant disease affecting bone and with no substantial impairment of
      mobility. Such patients were selected for the present study. Thirteen patients
      suffering from multiple sclerosis [11 females, two males; age 32 +/- 2 yr (mean
      +/- se)] and receiving iv methylprednisolone 15 mg/kg daily for 10 d completed
      the study. We measured serum osteocalcin (OC), aminoterminal propeptide of type I
      collagen (PINP), bone isoform of alkaline phosphatase (bALP), carboxyterminal
      telopeptide of type I collagen (CTX), and urinary calcium/creatinine ratio
      (uCa/Cr) during the 10-d cycle and 3 months later. Dual-energy x-ray
      absorptiometry and calcaneal quantitative ultrasonometry were performed before
      and 6 months after therapy. We found an immediate, impressive fall of OC and PINP
      (-80 +/- 3 and -54 +/- 5% at d 2, respectively), which persisted throughout the
      whole treatment period (P < 0.0001 for both markers). bALP levels showed only a
      modest decrease at d 6 (-19 +/- 7%, P < 0.05), with subsequent return to baseline
      in d 7-10. After 3 months, OC, PINP, and bALP levels rose to +51 +/- 22, +37 +/-
      16 (not significant), and +61 +/- 17% (P < 0.01) with respect to baseline,
      respectively. uCa/Cr and CTX showed a progressive, marked increase during
      treatment, peaking at d 7-9 (+92 +/- 44 and +149 +/- 63%, respectively), with
      subsequent decrement at d 10 (P < 0.01 and P < 0.05, respectively) despite
      continuing GC administration. After 3 months, uCa/Cr and CTX levels were also
      higher than baseline. No change in quantitative ultrasonometry parameters and
      bone mineral density was observed 6 months after therapy. In conclusion, high
      dose, short-term iv GC regimens cause an immediate and persistent decrease in
      bone formation and a rapid and transient increase of bone resorption. Our data
      also support the concept that discontinuation of such regimens is followed by a
      high bone turnover phase.

PMID- 15472187
TI  - Anterior pituitary dysfunction in survivors of traumatic brain injury.
AB  - Recent data suggest that anterior pituitary dysfunction after traumatic brain
      injury (TBI) is common. We sought to confirm the results of earlier studies in a
      larger cohort of patients with dynamic testing of pituitary function. We studied
      102 consecutive TBI survivors (85 males; median age 28, range 15-65 yr) who had
      survived severe or moderate TBI (initial Glasgow Coma Scale score 3-13) at a
      median of 17 months (range 6-36) post event. GH and ACTH reserves were initially
      assessed using the glucagon stimulation test (GST). Normative data on GH and
      cortisol responses to the GST were obtained from 31 matched healthy controls.
      Patients with subnormal GH or cortisol responses were further evaluated, using
      the insulin tolerance test (ITT) or arginine + GHRH test for GH assessment and
      the ITT or 250-microg short synacthen test for the assessment of ACTH reserve.
      Patients were considered to be GH or ACTH deficient if they failed both the GST
      and the second provocative test. Baseline thyroid function, prolactin, IGF-I,
      gonadotropins, testosterone, or estradiol was performed in all patients and
      compared with local reference ranges.In controls, normal response to the GST was
      a stimulated GH peak of greater than 5 microg/liter and cortisol peak greater
      than 450 nmol/liter (16 microg/dl). Eighteen TBI patients (17.6%) had GH response
      to the GST less than 5 microg/liter, 11 of whom also failed the ITT or the
      arginine + GHRH tests. GH-deficient patients had significantly higher body mass
      index (P = 0.003), and lower IGF-I concentrations (P < 0.001), than GH-sufficient
      patients. Twenty-three patients (22.5%) had cortisol responses to GST less than
      450 nmol/liter, 13 of whom also failed the ITT or short synacthen test. GH or
      ACTH deficiencies were not related to age, Glasgow Coma Scale score, or the
      presence of other pituitary hormone abnormalities (P > 0.05). Twelve patients
      (11.8%) had gonadotropin and one (1%) had thyrotrophin deficiencies. Twelve
      patients (11.8%) had hyperprolactinemia. Twenty-nine patients (28.4%) had at
      least one anterior pituitary hormone deficiency. This is the largest study, to
      date, of hypopituitarism after TBI and confirms a high prevalence of undiagnosed
      anterior pituitary hormone abnormalities in survivors of TBI. Hypopituitarism is
      a treatable cause of morbidity after TBI. In addition to conventional pituitary
      hormone replacement, the potential of GH treatment to enhance recovery needs to
      be examined in a prospective study.

PMID- 15472188
TI  - Peripheral blood monocyte vitamin D receptor levels are elevated in patients with
      idiopathic hypercalciuria.
AB  - Idiopathic hypercalciuria (IH) is the most common cause of calcium oxalate
      nephrolithiasis. Increased intestinal calcium absorption and bone resorption and
      decreased tubule calcium reabsorption may be caused by elevated serum 1,25
      dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] in some patients but not in those with
      normal serum 1,25(OH)(2)D(3) levels. Because 1,25(OH)(2)D(3) exerts its
      biological actions through binding to the cellular vitamin D receptor (VDR), the
      present study was undertaken to test the hypothesis that VDR levels are elevated
      in IH patients. Ten male IH calcium oxalate stone-formers were paired with
      controls matched in age within 5 yr and lacking a history of stones or family
      history of stones. Blood was obtained for serum, peripheral blood monocytes
      (PBMs) were separated from lymphocytes and other mononuclear cells, and PBM VDR
      content was measured by Western blotting. The PBM VDR level was 2-fold greater in
      IH men at 49 +/- 21 vs. 20 +/- 15 fmol/mg protein, mean +/- sd; P < 0.008. Serum
      1,25(OH)(2)D(3) levels were not higher than controls (48 +/- 14 vs. 39 +/- 11
      pg/ml; P < 0.068). In conclusion, PBM VDR levels are elevated in IH calcium
      oxalate stone-formers. The elevation could not be ascribed to increased serum
      1,25(OH)(2)D(3) levels. These results suggest that the molecular basis for IH
      involves a pathological elevation of tissue VDR level, which may elevate
      intestinal calcium absorption and bone resorption and decrease renal tubule
      calcium reabsorption. The mechanism for increased VDR in IH patients with normal
      serum 1,25(OH)(2)D(3) levels is unknown.

PMID- 15472189
TI  - Early manifestations of gastric autoimmunity in patients with juvenile autoimmune
      thyroid diseases.
AB  - Juvenile patients affected with autoimmune thyroid disorders showed a 14-21%
      prevalence of parietal cell antibodies (PCA) reacting against the H+/K+-ATPase of
      the gastric parietal cells. PCA are the principal immunological markers of
      atrophic body gastritis (ABG).ABG is characterized by loss of oxyntic glands,
      achlorhydria, and hypergastrinemia. The aim of this study was to determine
      whether PCA positivity could be associated with biochemical and histological
      manifestations of gastric autoimmunity in juvenile patients with autoimmune
      thyroid disease (AITD). We studied 129 children (96 females and 33 males) with
      chronic lymphocytic thyroiditis (n = 115) or Graves' disease (n = 14). Mean age
      at diagnosis of AITD was 9.7 +/- 3.3 yr, and mean age at sampling was 12.3 +/-
      3.7 yr. We determined PCA and Helicobacter pylori antibodies, gastrin, and
      pepsinogen I plasma levels. Gastroscopy with multiple biopsies was carried out in
      a subgroup of patients with PCA positivity. We found that 30% of children had
      detectable PCA. Hypergastrinemia was found in 45% of the PCA-positive children
      (range, 40-675 pg/ml) vs. 12% of PCA-negative children (range, 35-65 pg/ml; P <
      0.001). Eighteen patients with PCA positivity underwent gastroscopy; eight of
      these children had normogastrinemia, which showed no signs of ABG, and 10
      children had hypergastrinemia, of whom five had mild to severe ABG. Our study
      shows that autoimmune gastritis is an early event in juvenile AITD with
      detectable PCA. Gastrin plasma level is a reliable marker of gastric atrophy.

PMID- 15472190
TI  - Perturbed sex steroid status in men with idiopathic osteoporosis and their sons.
AB  - We reported previously that a gender-specific defect of acquisition of lumbar
      bone mass plays an important role in the pathogenesis of male idiopathic
      osteoporosis (IO) and that there is a strong heritability of this maturational
      defect, which is particularly manifest in sons of men with IO. A hypothetical
      role of an altered sex steroid status and/or of a (TTTA)(n)- repeat polymorphism
      of the aromatase (CYP19) gene in male IO remains to be established. We evaluated
      bone mineral density (BMD) at the lumbar spine and femoral neck in 64 male IO
      probands (selected on the basis of a z-score of -2 or less), 21 of their sons, 41
      of their brothers, and 126 healthy, age-matched controls. Serum testosterone (T),
      estradiol (E(2)), and SHBG levels were measured by immunoassays. Free T (FT) and
      free E(2) (FE(2)) levels were calculated from total T, E(2), SHBG, and albumin
      concentrations using a previously validated equation. Probands, sons, and
      brothers had lower body weight than age-matched controls, with mean differences
      of 5.0, 4.6, and 4.0 kg, respectively. In probands, sons, and brothers, SHBG
      levels were higher compared with controls. Significantly lower FE(2) levels were
      observed in probands and sons compared with their respective controls (P < 0.05
      and P < 0.01, respectively). The brothers had nonsignificantly lower FE(2) levels
      compared with their controls. In the total group of sons with significantly lower
      FE(2) levels, tertile analysis according to lumbar spine BMD showed that only in
      the subgroup of sons belonging to the lowest tertile both FE(2) and FT were
      decreased compared with their controls. The differences in FE(2) levels in IO
      probands and their sons remained significant after adjustment for body mass index
      (BMI), even though in multivariate analyses BMI was a major determinant of BMD.
      The frequency distribution of the CYP19 gene (TTTA)(n)- repeat length (determined
      by fragment analysis, GeneScan) was not different between men with IO and their
      controls. In conclusion, the finding of a relative FE(2) deficit in both men with
      IO as well as their affected sons, even after adjustment for BMI, suggests that
      estrogen-related perturbances may be involved in the pathogenesis of the
      deficient acquisition of peak bone mass in male IO.

PMID- 15472191
TI  - Endogenous levels of serum estradiol and sex hormone binding globulin determine
      bone mineral density, bone remodeling, the rate of bone loss, and response to
      treatment with estrogen in elderly women.
AB  - A total of 489 elderly women aged 65-75 yr who participated in a 3-yr,
      randomized, blinded osteoporosis trial underwent measurements of serum estradiol,
      bioavailable estradiol, and SHBG. At baseline, bone mineral density (BMD) was
      lower at the femoral sites (7-19%, P < 0.05), total body (6-8%, P < 0.05), and
      spine (5-9%, P = 0.2) in women in the lowest tertile for serum total estradiol
      [<9 pg/ml (33 pmol/liter)], serum bioavailable estradiol [<2.4 pg/ml (8.8
      pmol/liter)], or highest tertile for serum SHBG (>165 nmol/liter), compared with
      women in the highest tertiles of total estradiol [>13.3 pg/ml (49 pmol/liter)]
      and bioavailable estradiol [>4 pg/ml (14 pmol/liter)] or lowest tertile for SHBG
      (<113 nmol/liter). Bone markers were increased in women in the lowest tertile for
      serum total estradiol (not significant) and bioavailable estradiol (P < 0.05) and
      highest tertile for SHBG (P < 0.05). In the longitudinal study, the rate of bone
      loss in the placebo group was significantly higher in total body (P < 0.05) and
      spine (P < 0.05) in women in the lowest tertile, compared with the highest
      tertile of serum bioavailable estradiol. After treatment with conjugated equine
      estrogens 0.625 mg/d, the increase in BMD was 4-6% higher at the femoral sites (P
      < 0.05), total body (P < 0.05), and spine (not significant), in the lowest
      tertile, compared with the highest tertile of serum bioavailable estradiol or
      highest tertile, compared with the lowest tertile of serum SHBG. In summary,
      small variations in endogenous serum estradiol and high serum SHBG determine
      differences in BMD and rate of bone loss in elderly women and also affect the
      response to treatment with estrogen. Women with a serum estradiol level of less
      than 9 pg/ml (33 pmol/liter) are optimal candidates for estrogen therapy for
      osteoporosis prevention.

PMID- 15472192
TI  - Metabolic syndrome is associated with elevated oxidative stress and dysfunctional
      dense high-density lipoprotein particles displaying impaired antioxidative
      activity.
AB  - A metabolic syndrome (MetS) phenotype is characterized by insulin-resistance,
      atherogenic dyslipidemia, oxidative stress, and elevated cardiovascular risk and
      frequently involves subnormal levels of high-density lipoprotein (HDL)
      cholesterol. We evaluated the capacity of physicochemically distinct HDL
      subfractions from MetS subjects to protect low-density lipoprotein against
      oxidative stress.MetS subjects presented an insulin-resistant phenotype, with
      central obesity and elevation in systolic blood pressure and plasma triglyceride,
      LDL-cholesterol, apolipoprotein B, glucose, and insulin levels. Systemic
      oxidative stress, assessed as plasma 8-isoprostanes, was significantly higher
      (3.7-fold) in MetS subjects (n = 10) compared with nonobese normolipidemic
      controls (n = 11). In MetS, small, dense HDL3a, 3b, and 3c subfractions possessed
      significantly lower specific antioxidative activity (up to -23%, on a unit
      particle mass basis) than their counterparts in controls. In addition, HDL2a and
      3a subfractions from MetS patients possessed lower total antioxidative activity
      (up to -41%, at equivalent plasma concentrations). The attenuated antioxidative
      activity of small, dense HDL subfractions correlated with systemic oxidative
      stress and insulin resistance and was associated with HDL particles exhibiting
      altered physicochemical properties (core triglyceride enrichment and cholesteryl
      ester depletion). We conclude that antioxidative activity of small, dense HDL
      subfractions of altered chemical composition is impaired in MetS and associated
      with elevated oxidative stress and insulin resistance. Induction of selective
      increase in the circulating concentrations of dense HDL subfractions may
      represent an innovative therapeutic approach for the attenuation of high
      cardiovascular risk in MetS.

PMID- 15472193
TI  - Alterations in cortisol secretory dynamics in adolescent girls with anorexia
      nervosa and effects on bone metabolism.
AB  - Anorexia nervosa (AN) is associated with low bone density in adolescents and
      adults. Hypercortisolemia has been reported in adults with this disorder and has
      been hypothesized to be a factor in bone loss. However, the secretory dynamics of
      cortisol in adolescents with AN and the contribution of alterations in cortisol
      secretion to bone metabolism in AN have not been examined. We examined the
      dynamics of cortisol secretion by Cluster and deconvolutional analysis in 23
      girls with AN and 21 healthy adolescents of comparable age and maturity. Cortisol
      sampling was performed every 30 min for 12 h overnight. Twenty-four-hour urinary
      free cortisol (UFC) and creatinine (cr) were obtained for all subjects. The
      surface area (SA) of the subjects was calculated. Markers of bone turnover (type
      1 procollagen, osteocalcin, and N-telopeptide) were examined. Subjects with AN
      were prospectively followed over 1 yr, and those who recovered weight (defined as
      a 10% increase in body mass index) were again studied. On Cluster analysis, girls
      with AN had significantly higher mean cortisol (8.6 +/- 2.0 vs. 5.9 +/- 1.1
      microg/dl; P < 0.0001), nadir cortisol (5.5 +/- 2.3 vs. 3.4 +/- 1.2 microg/dl; P
      = 0.0008), valley mean cortisol (7.0 +/- 2.7 vs. 4.7 +/- 1.5 microg/dl; P =
      0.001), peak amplitude (12.6 +/- 4.4 vs. 7.8 +/- 3.0 microg/dl; P = 0.0004), peak
      area (652 +/- 501 vs. 340 +/- 238 microg/dl; P = 0.02), and total area under the
      curve (6112 +/- 1467 vs. 4117 +/- 802 microg/dl; P < 0.0001) than healthy
      adolescents. On deconvolutional analysis, the frequency of nocturnal secretory
      bursts (7.0 +/- 1.2 vs. 5.8 +/- 1.3 /12 h; P = 0.001), total nocturnal pulsatile
      cortisol secretion (69.3 +/- 14.7 vs. 53.9 +/- 11.1 microg/dl; P = 0.0003), and
      total cortisol secretion (89.6 +/- 18.8 vs. 71.2 +/- 17.6 microg/dl; P = 0.002)
      were significantly higher in girls with AN than in healthy controls. Cortisol
      half-life trended higher in girls with AN. However, basal cortisol secretion and
      approximate entropy did not differ between the groups. UFC/cr and UFC/cr.SA were
      significantly higher in girls with AN than in controls [0.050 +/- 0.028 vs. 0.036
      +/- 0.017 (P = 0.04) and 0.035 +/- 0.020 vs. 0.023 +/- 0.012 (P = 0.03)]. Six of
      23 girls with AN had UFC/cr.SA values that were more than 2 sd above those in
      healthy controls. An inverse correlation was noted between measures of cortisol
      concentration as well as pulsatile secretion and measures of nutritional status
      (body mass index, fat mass, leptin, insulin, and IGF-I). An oral glucose load
      suppressed cortisol levels in healthy adolescents, but not in AN patients. Weight
      recovery was associated with a significant decrease in the number of secretory
      bursts. In girls with AN, strong inverse correlations were noted between levels
      of cortisol (mean, nadir, and total area under the curve) and levels of markers
      of bone formation (C-terminal propeptide of type 1 procollagen and osteocalcin).
      Conversely, in healthy controls, cortisol values did not predict levels of
      markers of bone turnover. Adolescent girls with AN have significantly higher
      serum cortisol concentrations and UFC/cr.SA values than healthy adolescents. This
      increased cortisol concentration is a function of increased frequency of
      secretory bursts, resulting in increased pulsatile secretion. Hypercortisolemia
      appears to be a direct consequence of undernutrition and is associated with a
      decrease in markers of bone formation. Therefore, high cortisol values in AN may
      contribute to the low bone density observed in adolescents with this disorder by
      decreasing bone formation.

PMID- 15472194
TI  - Effects of the Trp64Arg polymorphism in the beta3-adrenergic receptor gene on
      insulin sensitivity in small for gestational age neonates.
AB  - To evaluate whether the Trp64Arg polymorphism in the beta3-adrenergic receptor
      (AR) gene is associated with decreased birth weight and might account for some of
      the association between birth weight and impaired insulin sensitivity, the beta3
      AR genotype was assessed in 296 neonates of singleton pregnancies, including 76
      neonates classified as small for gestational age (SGA) and 220 neonate classified
      as appropriate for gestational age (AGA). Fasting glucose and insulin levels were
      measured on d 3 after birth. The insulin levels and insulin-to-glucose ratio were
      significantly higher in the SGA group than in the AGA group. Frequency of the
      Trp64Arg allele was similar in the AGA and SGA groups (0.15 and 0.17,
      respectively). Moreover, when we adjusted for sex and gestational age, there was
      no significant difference in birth weight, fasting glucose, insulin levels, or
      insulin-to-glucose ratio between those with and without the mutation. However, in
      the SGA group, carriers of the Trp64Arg allele had significantly higher fasting
      insulin levels and insulin-to-glucose ratios than noncarriers (17.54 +/- 2.11 vs.
      13.18 +/- 1.47 microIU/ml, P < 0.05; and 4.89 +/- 0.60 vs. 3.14 +/- 0.42, P <
      0.05, respectively), whereas no association was detected for this polymorphism in
      the AGA group.SGA is an important factor that predisposes to insulin resistance,
      and the Trp64Arg beta3-AR gene polymorphism may contribute to insulin resistance
      associated with reduced fetal growth.

PMID- 15472195
TI  - Prevalence of pituitary deficiency in patients after aneurysmal subarachnoid
      hemorrhage.
AB  - After aneurysmal subarachnoid hemorrhage (SAH), patients frequently present with
      persistent bodily, psychosocial, and cognitive impairments that resemble those of
      patients with untreated partial or complete pituitary insufficiency. Because of
      these similarities, the authors hypothesized that aneurysmal SAH may cause
      pituitary dysfunction. Pituitary function testing was performed in 40 aneurysmal
      SAH patients between 12 and 72 months after the SAH. A combined TRH-LHRH-arginine
      test and the insulin tolerance test were performed on two separate days. Only 18
      of 40 (45%) of the tested patients had normal pituitary function. Five of 40
      exhibited isolated severe GH deficiency (GHD), and an additional three of 40 had
      severe GHD plus corticotroph deficiency. Isolated corticotroph deficiency was
      seen in 13 of 40 patients, and one patient showed isolated thyrotroph deficiency.
      All but one patient with corticotroph insufficiency were female. Patients with
      severe GHD had gained significantly more weight since their SAH than patients
      without GHD and exhibited a significantly higher body mass index. None of the
      clinical parameters indicative of a poor neurological outcome in aneurysmal SAH
      were related to pituitary insufficiency. In summary, neuroendocrine dysfunction
      was identified in a substantial portion of patients with previous aneurysmal SAH
      and should be borne in mind as a potential long-term sequel of the illness.

PMID- 15472196
TI  - Bone status and fracture prevalence in Russian adults with childhood-onset growth
      hormone deficiency.
AB  - The consequences of lifelong untreated childhood-onset GH deficiency (COGHD) on
      adult bone and especially fracture prevalence are largely unknown due to the lack
      of data on long-term outcome of untreated patients. Therefore, we studied adult
      Russian patients (n = 66; 28 females and 38 males) with idiopathic GH-untreated
      COGHD. Patients had isolated GH deficiency (IGHD; n = 18, age 23 +/- 10 yr) or
      multiple pituitary hormone deficiency (MPHD) with open (OMPHD; n = 27, age 23 +/-
      5 yr) or closed growth plates (CMPHD; n = 21, age 55 +/- 12 yr). Bone mineral
      content (BMC) and bone mineral density (BMD) values were compared with 821 normal
      Russian controls. Fracture prevalence was ascertained from medical history and
      compared with similar data from 333 normal controls. Height sd score was -4.6
      (range, -1.8 to -8.1). This represents 82% of the height of normal Russian
      adults. BMC of the lumbar spine, femoral neck, and total body of patients with
      IGHD was 54, 71, and 59%, respectively, of that of age- and sex-matched controls
      (all P < 0 0.001). A similarly decreased BMC (42-69% of expected values) was
      found for all bone regions of patients with both OMPHD and CMPHD. Mean areal BMD
      measurements (g/cm(2)) varied (Z scores between -1.8 and -3.0), but the
      calculated true bone density (g/cm(3)) was normal in patients with IGHD or CMPHD
      and only slightly decreased (Z score, -0.8) in patients with OMPHD. Lifetime low
      energy fracture prevalence was normal in patients with IGHD but substantially
      exceeded the expected prevalence in OMPHD (odds ratio of fracture = 3.0; 0.6
      fractures per patient; P < 0.0001) or CMPHD patients (odds ratio for fracture =
      7.4; 2.2 fractures per patient; P < 0.0001). In conclusion, IGHD and MPHD of
      childhood onset very substantially impair adult height and BMC. Although areal
      BMD is frankly decreased, volumetric bone density is unaffected, but
      nevertheless, the fracture prevalence in patients with MPHD is markedly
      increased. These observations demonstrate that not only volumetric density but
      also bone mass and shape are major determinants of bone strength.

PMID- 15472197
TI  - Adult heights attained by children with hypothalamic/chiasmatic glioma treated
      with growth hormone.
AB  - Hypothalamic/chiasmatic gliomas (H/CG) in children are commonly accompanied by
      endocrine dysfunction due to mass effects of the tumor itself or as a consequence
      of tumor therapy, with GH deficiency (GHD) being the most common disorder. We
      report the height outcomes of GH-treated H/CG patients with GHD. We reviewed the
      records of 14 GHD patients with H/CG who were treated with human GH. A comparison
      group of non-GH-treated H/CG patients was also identified. Heights were expressed
      as sd scores (SDS). For GH-treated patients, the mean initial height was -0.7 +/-
      0.3 (+/-se). Their mean final height was -0.3 +/- 0.3. The mean change in height
      SDS for the GH-treated group was +0.4. The mean initial and final height SDS for
      the non-GHD patients were 0.6 (se = 0.4) and 0.0 (se = 0.4), respectively. The
      mean change in height SDS was -0.6. The GHD patients had significantly lower
      initial height SDS compared with the non-GHD patients (P = 0.01) and had a
      significantly greater change in their height SDS (P = 0.04). GH treatment for
      H/CG patients restores much of their growth potential and improves adult height
      to within normal limits.

PMID- 15472198
TI  - Growth hormone deficiency predicts cardiovascular risk in young adults treated
      for acute lymphoblastic leukemia in childhood.
AB  - Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, and
      until recently prophylactic cranial radiotherapy (CRT) was important for
      achieving long-term survival. Hypothalamic-pituitary hormone insufficiency is a
      well-recognized consequence of CRT for childhood cancer. Another problem is
      increased cardiovascular risk, which has been shown in long-term survivors of
      other childhood cancers. In the only previously reported study on cardiovascular
      risk after childhood ALL, obesity and dyslipidemia were recorded in a small
      subgroup treated with CRT, compared with patients treated with chemotherapy. The
      mechanisms behind the increase in cardiovascular risk in survivors of childhood
      cancer are not clarified. The aim of the present study was to elucidate
      mechanisms of increased cardiovascular risk in former childhood ALL patients. A
      group of 44 ALL survivors (23 males, median age 25 yr, range 19-32 yr at the time
      of study) treated with CRT (median 24 Gy, 18-30 Gy) at a median age of 5 yr (1-18
      yr) and chemotherapy were investigated for prevalence of GH deficiency and
      cardiovascular risk factors. Comparison was made with controls randomly selected
      from the general population and individually matched for sex, age, smoking
      habits, and residence. All patients and controls underwent a GHRH-arginine test,
      and patients with a peak GH 3.9 microg/liter or greater were further investigated
      with an additional insulin tolerance test. Significantly higher plasma levels of
      insulin (P = 0.002), blood glucose (P = 0.01), and serum levels of low-density
      lipoprotein cholesterol, apolipoprotein (Apo) B, triglycerides, fibrinogen, and
      leptin (all P <or= 0.05) were recorded among the ALL patients, compared with
      controls. Furthermore, the serum levels of high-density lipoprotein cholesterol
      (P = 0.03) and Apo A1 (P = 0.005) were significantly lower among the patients.
      Compared with controls, the patients had higher body mass index and waist to hip
      ratio, and body composition measured with dual-energy x-ray absorptiometry showed
      significantly higher fat mass and lower lean mass (P < 0.001). Forty of 44 ALL
      patients (91%) were considered GH deficient according to the insulin tolerance
      test and/or the GHRH-arginine test, and the rest were considered GH insufficient.
      In patients, peak GH during GHRH-arginine was significantly negatively correlated
      to total body fat mass measured with dual-energy x-ray absorptiometry (r = -0.48,
      P = 0.001), waist to hip ratio (r = -0.32, P = 0.03), plasma insulin (r = -0.49,
      P = 0.001), and leptin (r = -0.46, P = 0.002). Moreover, a significantly positive
      correlation was recorded with high-density lipoprotein cholesterol (r = 0.38, P =
      0.012). Using Doppler echocardiography, a marked reduction in cardiac dimensions
      and performance (ejection fraction P < 0.001 and fractional shortening P = 0.01),
      compared with controls, was recorded. In conclusion, at a median 17 yr after
      treatment with CRT and chemotherapy in former childhood ALL patients, a
      significant increase in cardiovascular risk factors was recorded. We suggest that
      GH deficiency, induced by CRT, is a primary cause for this because strong
      correlations between the stimulated GH peak and several of the cardiovascular
      risk factors were observed.

PMID- 15472199
TI  - Metabolic and behavioral characteristics of metabolically obese but normal-weight
      women.
AB  - A unique subset of individuals termed metabolically obese but normal weight
      (MONW) has been identified. These young women are potentially at increased risk
      for development of the metabolic syndrome despite their young age and normal body
      mass index. We seek to determine metabolic and behavioral factors that could
      potentially distinguish MONW women from young women with a normal metabolic
      profile.Ninety-six women were classified as MONW (n = 12) or non-MONW (n = 84)
      based on a cut point of insulin sensitivity (as estimated by the homeostasis
      model assessment). Potentially distinguishing phenotypes between groups measured
      included serum lipids, ghrelin, leptin, adiponectin, body composition and body
      fat distribution, resting and physical activity energy expenditure, peak oxygen
      uptake, dietary intake, dietary behavior, and family history and lifestyle
      variables. Despite a similar body mass index between groups, MONW women showed
      higher percent body fat, lower fat-free mass, lower physical activity energy
      expenditure, and lower peak oxygen uptake than non-MONW women. Plasma cholesterol
      level was higher in MONW women, whereas no differences were noted for other blood
      lipids, ghrelin, leptin, adiponectin, and resting energy expenditure. MONW women
      had lower dietary restraint scores than non-MONW women, but no differences were
      noted in disinhibition, hunger, and dietary intake. Stepwise regression analysis
      performed on all subjects showed that 33.5% of the unique variance of the
      homeostasis model assessment was explained with the variables of percentage of
      body fat (17.1%), level of dietary restraint (10.4%), and age (6%). Both
      metabolic and dietary behavioral variables contribute to the deleterious
      metabolic profile of MONW women. They display lower insulin sensitivity due
      potentially to a cluster of sedentary behavior patterns that contribute to their
      higher adiposity. Furthermore, cognitive attitudes toward food (i.e. dietary
      restraint) and concomitant lifestyle behaviors may play a role in regulating
      insulin sensitivity in MONW women.

PMID- 15472200
TI  - Effects of atorvastatin on fasting plasma and marginated apolipoproteins B48 and
      B100 in large, triglyceride-rich lipoproteins in familial combined
      hyperlipidemia.
AB  - Large triglyceride (TG)-rich lipoproteins (TRLs) circulate in the blood, but they
      may also be present in a marginated pool, probably attached to the endothelium.
      It is unknown whether statins can influence this marginated pool in vivo in
      humans. Intravenous fat tests were performed in familial combined hyperlipidemia
      (FCHL) subjects before and after atorvastatin treatment and in controls to
      investigate whether acute increases in apoB in TRL fractions would occur,
      potentially reflecting the release of this TRL from a marginated pool. After a 12
      h fast, a bolus injection of 10% Intralipid was given to 12 FCHL patients before
      and after 16-wk treatment with atorvastatin. Twelve carefully matched controls
      were included. For 60 min postinjection, apoB48, apoB100, and lipids were
      measured in TRLs. Fasting apoB100 in all TRL fractions were 2- to 3-fold higher
      in untreated FCHL compared with controls. ApoB48 concentrations in chylomicron
      fractions increased significantly within 10 min in FCHL before and after
      treatment, but not in controls. ApoB100 increased significantly in the
      chylomicron fractions in untreated FCHL and in controls, but not in FCHL after
      treatment. In very low density lipoprotein 1, apoB100 increased only in untreated
      FCHL. In very low density lipoprotein 2, apoB100 did not change in any group.
      These data show that increasing the number of circulating TRLs by chylomicron
      like particles, results in increased plasma apoB-TRLs, probably by acute release
      from a marginated pool. This is a physiological process occurring in FCHL and in
      healthy normolipidemic subjects, but it is more pronounced in the former.
      Decreased marginated TRL particles in FCHL is a novel antiatherogenic property of
      atorvastatin.

PMID- 15472201
TI  - Prevalence of adrenocorticotropin deficiency in children with idiopathic growth
      hormone deficiency.
AB  - We sought to determine the prevalence of ACTH deficiency in children with GH
      deficiency (GHD) of unknown etiology with and without TSH deficiency and to
      correlate the structural characteristics of the hypothalamic-pituitary region on
      magnetic resonance imaging (MRI) with TSH and ACTH status. The electronic medical
      records system of a children's hospital was used to identify all patients less
      than 18 yr of age with GHD. TSH and ACTH deficiency were defined as being present
      if the patient was prescribed replacement hormone therapy. The medical records of
      236 GHD subjects were reviewed, and the results of their MRI scans were recorded.
      Ninety had hypothalamic-pituitary-adrenal axis testing, and nine were ACTH
      deficient (10% of those tested; 4% of all subjects). Twenty-one (9%) of 236 were
      TSH deficient. All of the ACTH-deficient subjects were also TSH deficient: eight
      of nine had a gross abnormality on MRI, and one did not have an MRI report in the
      medical record. We conclude that patients with GHD, normal thyroid function, and
      no gross abnormalities on MRI do not need hypothalamic-pituitary-adrenal testing
      because no ACTH-deficient subjects would have been missed using this strategy
      (95% confidence interval, 0-5%).

PMID- 15472202
TI  - Administration of acylated ghrelin reduces insulin sensitivity, whereas the
      combination of acylated plus unacylated ghrelin strongly improves insulin
      sensitivity.
AB  - We investigated the metabolic actions of ghrelin in humans by examining the
      effects of acute administration of acylated ghrelin, unacylated ghrelin, and the
      combination in eight adult-onset GH-deficient patients. We followed glucose,
      insulin, and free fatty acid concentrations before and after lunch and with or
      without the presence of GH in the circulation. We found that acylated ghrelin,
      which is rapidly cleared from the circulation, induced a rapid rise in glucose
      and insulin levels. Unacylated ghrelin, however, prevented the acylated ghrelin
      induced rise in insulin and glucose when it was coadministered with acylated
      ghrelin. Surprisingly, the injection of acylated ghrelin induced an acute
      increase in unacylated ghrelin and therefore total ghrelin levels. Finally,
      acylated ghrelin decreased insulin sensitivity up to the end of a period of 6 h
      after administration. This decrease in insulin sensitivity was prevented by
      coinjection of unacylated ghrelin. This combined administration of acylated and
      unacylated ghrelin even significantly improved insulin sensitivity, compared with
      placebo, for at least 6 h, which warrants studies to investigate the long-term
      efficacy of this combination in the treatment of disorders with disturbed insulin
      sensitivity.

PMID- 15472203
TI  - Increased plasma concentration of macrophage migration inhibitory factor (MIF)
      and MIF mRNA in mononuclear cells in the obese and the suppressive action of
      metformin.
AB  - The objective of the study was to determine whether plasma migration inhibitor
      factor (MIF) concentration and mononuclear cell (MNC) mRNA are elevated in
      obesity and whether treatment with metformin reduces plasma MIF concentration.
      Forty obese subjects [body mass index (BMI), 37.5 +/- 4.9 kg/m(2)] and 40
      nonobese healthy subjects (BMI, 22.6 +/- 3.4 kg/m(2)) had their plasma MIF,
      glucose, insulin, free fatty acids (FFAs) and C-reactive protein (CRP)
      concentrations measured. Sixteen obese patients and 16 nonobese healthy subjects
      had RNA prepared from MNCs. Eight obese subjects with normal glucose
      concentration were treated with metformin 1 g (Glucophage XR; 1000 mg twice
      daily) twice daily for 6 wk. Eight obese subjects were used as controls. Plasma
      concentration of glucose, insulin, FFAs, and MIF was measured by appropriate
      assays. mRNA for MIF was measured by real-time PCR. Forty obese subjects had a
      fasting concentration of MIF of 2.8 +/- 2.0 ng/ml, whereas 40 nonobese subjects
      had a fasting MIF concentration of 1.2 +/- 0.6 ng/ml (P < 0.001). Plasma MIF
      concentrations were significantly related to BMI (r = 0.52; P < 0.001). mRNA for
      MIF was correlated to plasma FFAs (r = 0.40; P < 0.05) and plasma CRP (r = 0.42;
      P < 0.05) concentrations. Eight obese subjects had their fasting blood samples
      taken before and after taking a slow-release preparation of metformin at 1, 2, 4,
      and 6 wk. The mean plasma concentration fell from 2.3 +/- 1.4 to 1.6 +/- 1.2
      ng/ml at 6 wk (P < 0.05). Obese subjects not on treatment with metformin showed
      no change. During the period of treatment with metformin, the body weight did not
      change and the plasma concentration of glucose, insulin, and FFAs did not alter.
      We conclude that: 1) plasma MIF concentrations and MIF mRNA expression in the
      MNCs are elevated in the obese, consistent with a proinflammatory state in
      obesity; 2) these increases in MIF are related to BMI, FFA concentrations, and
      CRP; 3) metformin suppresses plasma MIF concentrations in the obese, suggestive
      of an antiinflammatory effect of this drug; and 4) this action of metformin may
      contribute to a potential antiatherogenic effect, which may have implications for
      the reduced cardiovascular mortality observed with metformin therapy in type 2
      diabetes mellitus.

PMID- 15472204
TI  - Elevated resting and exercise-induced cortisol levels after mineralocorticoid
      receptor blockade with canrenoate in healthy humans.
AB  - Activation of central nervous mineralocorticoid receptors (MRs) has been shown to
      inhibit the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis in
      animals. Here, we examined whether MRs in humans likewise regulate HPA activity
      in response to a physiological stressor. In a balanced, randomized, double-blind,
      cross-over trial, 12 healthy men were treated with either two injections of 200
      mg canrenoate or placebo 24 and 8 h before an intense physical exercise taking
      place between 1600 and 1700 h. Exercising was preceded by a 60-min rest period
      and followed by another 90-min rest. Blood was collected in regular intervals to
      determine ACTH, cortisol, and human GH (hGH). Exercise induced a significant rise
      in cortisol, ACTH, and hGH. Cortisol levels, however, were significantly higher
      after canrenoate, compared with placebo, whereas ACTH and hGH concentrations did
      not differ. The increase in cortisol was already significant during rest before
      exercise and continued to be elevated throughout the whole experiment. We
      conclude that MR blockade leads to a tonically increased cortisol secretion both
      during rest and under stimulation. The undiminished concentration of ACTH in the
      presence of elevated cortisol levels suggests that blockade of MR shifts the set
      point for cortisol feedback inhibition of the HPA axis toward higher cortisol
      levels.

PMID- 15472205
TI  - Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G
      with type 2 diabetes.
AB  - Elevated blood concentrations of IL-6 have been shown to predict type 2 diabetes.
      Because the impact of IL-6 gene polymorphisms on diabetes status, parameters of
      the metabolic syndrome, and low-grade systemic inflammation has not been analyzed
      in a population-based study, we investigated the association of the IL-6 single
      nucleotide polymorphisms C-174G and A-598G on these parameters in 704 elderly
      participants of the Kooperative Gesundheitsforschung im Raum Augsburg/Cooperative
      Research in the Region of Augsburg (KORA) Survey 2000. Both -174G and -598G
      alleles were significantly associated with type 2 diabetes (-174G: odds ratio =
      1.51, 95% confidence interval = 1.11-2.07, P = 0.0096; -598G: odds ratio = 1.56,
      95% confidence interval = 1.13-2.15, P = 0.0069) but not with impaired glucose
      tolerance. In subgroup analyses, the association reached statistical significance
      in men and in leaner subjects (body mass index <or= 28.7 kg/m(2), i.e. study
      median) but not in women or more obese persons. Circulating IL-6 levels were not
      associated with the IL-6 polymorphisms, but significantly elevated levels of the
      chemokine monocyte chemoattractant protein-1/CC chemokine ligand 2 in carriers of
      the protective genotypes indicated an indirect effect of these single nucleotide
      polymorphisms on the innate immune system. Our findings confirm that immune gene
      polymorphisms can be considered as independent risk factors in the etiology of
      type 2 diabetes and suggest that their contribution may be indirect, by
      influencing the levels of other immune mediators like monocyte chemoattractant
      protein-1.

PMID- 15472206
TI  - Pioglitazone and sodium salicylate protect human beta-cells against apoptosis and
      impaired function induced by glucose and interleukin-1beta.
AB  - Decreased functional beta-cell mass in type 1 and type 2 diabetes is due to beta
      cell apoptosis and impaired secretory function suggested to be mediated, in part,
      by immune- and/or high-glucose-induced production of IL-1beta acting through the
      nuclear factor kappaB (NFkappaB)/Fas pathway. The aim of this study was to
      determine whether two drugs believed to block NFkappaB activation, the
      thiazolidinedione (glitazone) pioglitazone and the nonsteroidal antiinflammatory
      drug sodium salicylate, can protect human beta-cells against the toxic effects of
      IL-1beta and high glucose in vitro. Human islets were maintained in culture 2-4 d
      at 100 mg/dl (5.5 mm) glucose with or without (control) IL-1beta or at 600 mg/dl
      (33.3 mm) glucose. IL-1beta and 600 mg/dl glucose increased beta-cell apoptosis
      and abolished short-term glucose-stimulated insulin secretion. Both drugs
      protected partially against loss of glucose-stimulated insulin secretion and
      prevented completely increased apoptosis caused by IL-1beta or 600 mg/dl glucose.
      IL-1beta secretion from islets was increased by 4-d culture at 600 mg/dl, and
      this was blocked by pioglitazone. Both drugs prevented activation of beta-cell
      NFkappaB by high glucose. Pioglitazone and sodium salicylate thus protect human
      islets against the detrimental effects of IL-1beta and high glucose by blocking
      NFkappaB activation and may therefore be useful in retarding the manifestation
      and progression of diabetes.

PMID- 15472207
TI  - Differential distribution of follistatin isoforms: application of a new FS315
      specific immunoassay.
AB  - Follistatin (FST) is a monomeric activin-binding and neutralization protein that
      has at least three isoforms in human tissues and fluids. The full-length FS315
      protein has an acidic 26-residue C-terminal tail that is not present in the
      shortest form, FS288, due to alternative splicing. An intermediate form, FS303,
      was identified in follicular fluid that is presumably derived by proteolytic
      processing of this tail domain. Interestingly, the biochemistry of each of these
      three isoforms is distinct, including their ability to bind to cell surface
      proteoglycans, an activity that ranks in the order FS288 > FS303 > FS315. This
      would suggest that the soluble, circulating FST isoform is likely to be FS315, a
      hypothesis supported by previous determinations that the serum and follicular
      fluid forms of FST are biochemically distinct. To test this hypothesis, we
      developed an immunoassay that is specific for full-length FS315. This assay was
      validated for use with human serum and follicular fluid samples and then used to
      examine FST in these fluid compartments. Our results indicate that FS315 is
      indeed the major circulating FST isoform but is undetectable in follicular fluid
      samples aspirated from normal women or women with polycystic ovary syndrome.
      These observations confirm the compartmentalization of FST isoforms according to
      their biochemical properties and biological actions so that the most soluble form
      is found in the circulation, whereas the forms that bind to cell surface
      proteoglycans are found in tissue compartments such as the ovarian follicle. They
      also confirm that the source of FST in human serum is not the ovarian follicle.

PMID- 15472208
TI  - Immunoglobulins from patients with Graves' disease induce hyaluronan synthesis in
      their orbital fibroblasts through the self-antigen, insulin-like growth factor-I
      receptor.
AB  - A distinctive histopathological feature associated with thyroid-associated
      ophthalmopathy is the disordered accumulation of the glycosaminoglycan,
      hyaluronan, in orbital connective tissues. This often occurs in the context of
      dramatic inflammation and tissue remodeling. Orbital fibroblasts exhibit a novel
      phenotype including exaggerated responses to cytokines. Here, we report for the
      first time the ability of IgG isolated from the sera of patients with Graves'
      disease (GD-IgG) to provoke in orbital fibroblasts the synthesis of hyaluronan.
      The effect of GD-IgG can be reproduced by IGF-I, appears to be mediated through
      the IGF-I receptor, and is abolished with glucocorticoid treatment. TSH failed to
      influence the synthesis of hyaluronan. In contrast to the effects in GD
      fibroblasts, cultures derived from donors without known thyroid disease fail to
      respond to GD-IgG or IGF-I. The observation that hyaluronan production is induced
      by GD-IgG in fibroblasts suggests that the IGF-I receptor and its activating
      antibodies may represent a key pathway through which important pathogenic events
      in thyroid-associated ophthalmopathy are mediated.

PMID- 15472209
TI  - Mannose-binding lectin gene polymorphisms are associated with gestational
      diabetes mellitus.
AB  - Insulin resistance is a feature of gestational diabetes mellitus (GDM). Inverse
      correlations between indexes of insulin sensitivity and serum markers of
      inflammation have been observed and, particularly, TNF-alpha has been shown to be
      associated with the appearance of insulin resistance in pregnancy. Mannose
      binding lectin (MBL) is a protein member of the collectin family. Its deficiency
      is genetically determined and predisposes to recurrent infections and chronic
      inflammatory diseases. To test the hypothesis that a genetic predisposition to a
      proinflammatory state could favor the appearance of GDM during pregnancy, we
      studied R52C and G54D polymorphisms of MBL2 gene and plasma MBL levels from 105
      consecutive GDM women and 173 healthy pregnant women. An association was found
      between G54D and GDM [odds ratio, 2.03 (1.18-3.49); P < 0.01], and this
      association remained significant when the presence of both mutated alleles was
      considered [odds ratio, 1.76 (1.04-2.96); P < 0.05] but not for the R52C. GDM
      patients who carried the G54D mutation required insulin therapy more frequently
      (56.4 vs. 30.4%, chi(2) =5.83; P = 0.027) and had heavier infants (3326.4 +/-
      546.9 vs. 3087.5 +/- 395.5 g; P < 0.05) than GDM women homozygous for the wild
      type allele. An inverse correlation in GDM patients between neonatal weight and
      plasma MBL levels (r = -0.320; P = 0.002) was found, remaining significant after
      adjustment for confounding variables. In conclusion, pregnant women bearing the
      G54D MBL allele have a greater risk for developing GDM and having heavier
      infants.

PMID- 15472210
TI  - Lecithin/cholesterol acyltransferase induces estradiol esterification in high
      density lipoprotein, increasing its antioxidant potential.
AB  - Endogenous estrogens protect against atherosclerosis, but the exact mechanisms
      remain unclear. One possibility is inhibition of lipoprotein oxidation. To act as
      antioxidants, estrogens reportedly need to be converted to lipophilic estrogen
      fatty acyl esters in a reaction catalyzed by lecithin/cholesterol acyltransferase
      (LCAT). To demonstrate directly that estradiol (E2) esters formed by LCAT and
      incorporated in high-density lipoprotein (HDL) increase its antioxidant
      potential, we investigated the copper-induced oxidation of purified HDL after
      incubations of: 1) HDL alone; 2) HDL in the presence of exogenous E2; 3) HDL in
      the presence of exogenous LCAT; 4) HDL in the presence of both E2 and LCAT; and
      5) HDL in the presence of E2, LCAT, and the LCAT inhibitor DTNB. We used this in
      vitro model system with supraphysiological concentrations of E2 and purified LCAT
      to produce E2 ester-containing HDL particles for studies of oxidation resistance.
      The lag time of HDL oxidation significantly increased with increasing contents of
      HDL-associated E2 esters. In conclusion, our results clearly demonstrated the
      role of LCAT in E2 esterification and its involvement in antioxidant protection
      of HDL. Elucidation of the possible in vivo role of HDL-associated estrogen
      esters requires further critical studies including experiments with physiological
      hormone concentrations.

PMID- 15472212
TI  - Effects of modified sham feeding on ghrelin levels in healthy human subjects.
AB  - The mechanisms involved in the preprandial rise and postprandial fall of
      circulating ghrelin levels are as yet unknown. Many hormonal and metabolic
      responses to nutrient intake begin during the cephalic or preabsorptive phase and
      are mostly mediated by the autonomous nervous system. The aim of the present
      study was to investigate the effects of the cephalic phase on ghrelin response to
      feeding in human subjects. The modified sham feeding (MSF), a well established
      technique in which nutrients are smelled, chewed, and tasted, but not swallowed,
      was used. Sixteen healthy volunteers (seven men and nine women; mean age +/- sd:
      31 +/- 8 yr; body mass index, 22 +/- 3 kg/m(2)) were studied after overnight
      fasting. Seven of them received a standardized mixed meal, and nine underwent
      MSF. Blood samples for ghrelin, insulin, and glucose were taken at time -30, 0,
      15, 30, 45, 60, 120 min during both tests. Pancreatic polypeptide determinations
      were evaluated at all times as markers of vagal activity only during MSF. Ghrelin
      levels significantly increased from time -30 to 0 min before the two tests, then
      significantly decreased: after the real feeding from 933 +/- 479 pg/ml (277 +/-
      142 pmol/liter) to 455 +/- 185 pg/ml (135 +/- 55 pmol/liter; P < 0.05), and after
      the sham feeding from 917 +/- 313 pg/ml (272 +/- 93 pmol/liter) to 519 +/- 261
      pg/ml (154 +/- 77 pmol/liter; P < 0.05). There were no significant differences
      between the patterns of the responses as evaluated by ANOVA (P = 0.863). As
      expected after MSF, plasma pancreatic polypeptide concentrations promptly
      increased from 58 +/- 29 pg/ml (14 +/- 7 pmol/liter) to 113 +/- 38 pg/ml (27 +/-
      9 pmol/liter) at 15 min (P < 0.01). Both insulin and glucose levels increased
      during the actual mixed meal, whereas they were not significantly modified by
      MSF. In conclusion, circulating ghrelin concentrations are decreased by sham
      feeding as they are by real feeding in humans. These findings underline the
      importance of the cephalic response to nutrient intake, i.e. the role of vagal
      activity, in the control of ghrelin secretion.

PMID- 15472211
TI  - Down-regulation of interleukin-1 receptor type 1 expression causes the
      dysregulated expression of CXC chemokines in endometriotic stromal cells: a
      possible mechanism for the altered immunological functions in endometriosis.
AB  - To evaluate the involvement of chemokines in the pathogenesis of endometriosis,
      we investigated the expression of CXC chemokines in cultured ovarian
      endometriotic cyst stromal cells (ECSC), endometrial stromal cells with
      endometriosis (ESCwE), and normal endometrial stromal cells (NESC). Using ELISA,
      TNF-alpha significantly enhanced the production of IL-8, growth-related oncogene
      alpha, and epithelial neutrophil-activating peptide-78 in all cases of ECSC (n =
      10), ESCwE (n = 6), and, NESC (n = 10). IL-1beta did not affect the production of
      these chemokines in eight of 10 cases of ECSC. In contrast, IL-1beta
      significantly enhanced the expression of these chemokines in all cases of ESCwE
      (n = 6) and NESC (n = 10). Western blot analysis revealed down-regulation of
      expression of IL-1 receptor type 1 (IL-1-R1) in all cases of ECSC with low
      response to IL-1beta (n = 8). In contrast, significant IL-1-R1 expression was
      detected in all cases of NESC. Although IL-1-R1 expression was detected in all
      cases of ESCwE (n = 6), its expression in ESCwE tended to decrease compared with
      that in NESC. Moreover, phosphorylation of inhibitor kappaB-alpha was detected in
      all cases of ESCwE and NESC after stimulation with IL-1beta, but not in ECSC with
      low response to IL-1beta (n = 8). In contrast, significant IL-1-R2 expression was
      detected in all cases of ECSC, ESCwE, and NESC. The present findings suggest that
      the dysregulation of IL-1/IL-1-R system relates to immunological dysfunction in
      endometriosis. The alteration of the CXC chemokines expression may be important
      for elucidation of the pathogenesis of endometriosis.

PMID- 15472213
TI  - Linkage between cryptorchidism, hypospadias, and GGN repeat length in the
      androgen receptor gene.
AB  - Although sufficient androgen receptor (AR) function is crucial for normal male
      sexual differentiation, single-point mutations in the AR gene are infrequent in
      the two most common male congenital malformations, hypospadias and
      cryptorchidism. Because polymorphic CAG and GGN segments regulate AR function, we
      investigated whether there was any association between these polymorphisms and
      mentioned malformations. Genotyping was performed by direct sequencing of DNA
      from patients diagnosed with hypospadias (n = 51) and cryptorchidism (n = 23) and
      controls (n = 210). The subjects with hypospadias were divided into subgroups of
      glanular, penile, and penoscrotal hypospadias. Median GGN lengths were
      significantly higher (24 vs. 23) among both subjects with cryptorchidism,
      compared with controls (P = 0.001), and those with penile hypospadias, compared
      with either controls (P = 0.003) or glanular and penoscrotal hypospadias combined
      (P = 0.018). The frequency of cases with GGN 24 or more vs. GGN = 23, differed
      significantly among those with cryptorchidism (65/35%), compared with controls
      (31/54%) (P = 0.012), and among subjects with penile hypospadias (69/31%),
      compared with either controls (P = 0.035) or glanular or penoscrotal hypospadias
      combined (32/55%) (P = 0.056). There were no significant differences in CAG
      lengths between the cases and controls. Our findings indicate an association
      between GGN length and the risk of cryptorchidism and penile hypospadias, both
      conditions considered consequences of low androgenicity.

PMID- 15472214
TI  - Lack of an association between peroxisome proliferator-activated receptor-gamma
      gene Pro12Ala polymorphism and adiponectin levels in the polycystic ovary
      syndrome.
AB  - Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic
      diseases and is characterized by obesity in approximately 50% of those affected.
      Adiponectin is an adipocyte-derived protein that possesses an antiatherosclerotic
      action and improves insulin sensitivity. Peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma) regulates the transcription of several adipocyte
      specific genes. The aim of this study was to investigate the putative influence
      of the PPAR-gamma gene Pro12Ala polymorphism on the adiponectin levels in PCOS
      and healthy women. One hundred twenty women with PCOS and 120 healthy women whose
      ages and body mass indexes matched those of the PCOS patients were investigated.
      The genetic analysis of PPAR-gamma gene Pro12Ala polymorphism was performed by
      restriction fragment of polymorphisms. Serum adiponectin levels were evaluated,
      and the homeostasis model assessment score was also calculated. No subject was
      homozygous for the Ala12 allele of the PPAR-gamma gene. No significant
      differences in body mass index, plasma glucose and lipid levels, and homeostasis
      model assessment scores were observed between and within genotype groups in PCOS
      and control women. No significant differences in serum adiponectin concentrations
      were observed between and within genotype groups in PCOS and control women. In
      conclusion, our results confirm that adiponectin concentrations are similar in
      PCOS and controls and demonstrate no effect of the PPAR-gamma gene Pro12Ala
      polymorphism on serum adiponectin levels.

PMID- 15472215
TI  - Human monoclonal thyroglobulin autoantibodies: epitopes and immunoglobulin genes.
AB  - Autoantibodies to thyroglobulin (TgAbs) are common markers of thyroid
      autoimmunity, but relatively few human monoclonal TgAbs have been described. From
      a panel of 64 human monoclonal TgAbs (isolated from a thyroid-disease derived
      combinatorial Ig gene library), we selected seven with unique genetic features
      for detailed characterization. These TgAbs preferentially recognize native (not
      denatured) Tg, like serum autoantibodies. Most have high affinities for Tg
      (dissociation constant 10(-10) to 10(-9) m). Their light (L) chain Ig genes are
      not unusual, but four of the five heavy (H) chain genes are new. Moreover, one H
      chain belongs to the small VH2 family, not previously reported for autoantibodies
      to Tg or thyroid peroxidase. The TgAbs inhibit the binding to Tg of the thyroid
      donor's serum autoantibodies, indicating epitopic overlap. Competition analysis
      (surface plasmon resonance) shows that the TgAbs recognize overlapping epitopes
      in an immunodominant region on the Tg dimer ( approximately 660 kDa). Two major
      and several minor epitopic regions were defined, each associated with a
      particular H + L chain combination. In conclusion, our TgAb panel provides novel
      information regarding the repertoire of H chain genes encoding human TgAbs as
      well as the relationship between the H chains and the epitopes recognized on this
      major thyroid autoantigen.

PMID- 15472216
TI  - Growth hormone treatment improves peripheral muscle oxygen extraction-utilization
      during exercise in patients with human immunodeficiency virus-associated wasting:
      a randomized controlled trial.
AB  - The arteriovenous oxygen difference (a-vO(2) difference), a measure of peripheral
      muscle oxygen extraction-utilization during exercise, is reduced in
      antiretroviral-treated patients with human immunodeficiency virus (HIV), thus
      causing a shift in the cardiac output-oxygen consumption (Q-VO(2)) relationship.
      We investigated the impact of recombinant human GH (rhGH) treatment on a-vO(2)
      difference and the Q-VO(2) relationship during submaximal exercise by randomizing
      12 HIV-infected patients (mean +/- sem: age, 43.3 +/- 1.5 yr; body mass, 69.5 +/-
      2.9 kg; body mass index, 22.4 +/- 0.9 kg/m(2); maximum oxygen consumption, 33.6
      +/- 1.5 ml/kg x min), with documented unintentional weight loss (>or=10% within
      the preceding 12 months) despite antiretroviral therapy, to receive 3 months of
      rhGH (6 mg/d) in a double-blind, placebo-controlled, cross-over trial. We
      assessed Q (determined noninvasively using CO(2) rebreathing), and subsequently a
      vO(2) difference, from Q-VO(2) relationships. At study entry, the mean slope (8.1
      +/- 1.0 liters/min x 1-liter increase in VO(2)) and intercept (3.1 +/- 1.3
      liters/min), generated from each patient's Q-VO(2) relationship, were greater and
      lower, respectively, than those reported for healthy individuals (6.0 and 4.0,
      respectively), thereby indicating a deficit in the a-vO(2) difference. After 3
      months of rhGH treatment, the slope decreased to 7.0, and the intercept increased
      to 3.5. After 1 month of rhGH treatment, the a-vO(2) difference (at a VO(2) of
      1250 ml/min) significantly (P < 0.05) increased (17.1 +/- 8.9%) from baseline
      (9.92 +/- 0.51 ml/dl) and remained elevated (10.39 +/- 0.48 ml/dl) after 3 months
      of treatment. No significant changes were seen with placebo. Therefore, treatment
      with rhGH leads to an improvement in peripheral muscle oxygen extraction
      utilization and the Q-VO(2) relationship during exercise in patients with HIV
      associated wasting despite antiretroviral therapy.

PMID- 15472217
TI  - Role of hexosamines in insulin resistance and nutrient sensing in human adipose
      and muscle tissue.
AB  - It has been proposed that the hexosamine pathway acts as a nutrient-sensing
      pathway, protecting the cell against abundant fuel supply, and that accumulation
      of hexosamines represents a biochemical mechanism by which hyperglycemia and
      hyperlipidemia induce insulin resistance. We hypothesized that if an increased
      flux through the hexosamine pathway caused insulin resistance in humans, the
      hexosamine levels should be increased in adipose and/or muscle tissue in insulin
      resistant subjects, such as patients with type 2 diabetes and obese individuals.
      In addition, we reasoned that if the hexosamine pathway were a nutrient-sensing
      pathway, hexosamine levels in adipose and skeletal muscle tissue should be
      correlated with levels of circulating nutrients, such as glucose and free fatty
      acids (FFAs) and leptin concentrations. In a human cross-sectional study of 55
      patients [20 with type 2 diabetes mellitus (DM) and 21 normal-lean (NL) and 14
      normal-obese (NO) subjects] who underwent hip replacement surgery, adipose and
      muscle tissue biopsies were obtained and analyzed for levels of hexosamines [UDP
      N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine] and hexoses (UDP
      glucose and UDP-galactose). Fasting plasma glucose, glycosylated hemoglobin,
      serum insulin and homeostasis model assessment calculations, serum lipids, and
      leptin were measured on the same day. Hexosamines were not elevated in adipose
      and muscle tissue of patients with type 2 DM compared with NL and NO subjects
      (UDP-GlcNac DM vs. NL vs. NO, 3.3 +/- 2.3 vs. 2.2 +/- 2.1 vs. 3.0 +/- 2.0 nmol/g
      tissue in adipose tissue and 8.1 +/- 2.9 vs. 7.8 +/- 2.8 vs. 7.6 +/- 2.8 nmol/g
      tissue in muscle tissue, respectively). Hexosamines in adipose tissue were
      positively correlated with circulating levels of FFA (UDP-GlcNAc, r = 0.33, P <
      0.05; UDP-N-acetylgalactosamine, r = 0.41, P < 0.01). Adipose tissue UDP-GlcNAc
      was correlated with leptin levels (r = 0.33; P < 0.05). No such relationship was
      identified in muscle tissue. In conclusion, these findings argue against a
      pathophysiological role of the hexosamine pathway in insulin resistance in humans
      but support the hypothesis that the hexosamine pathway in adipose tissue, not in
      muscle, is a FFA-sensing pathway and could be involved in the regulation of
      leptin expression.

PMID- 15472218
TI  - Role of sympathetic neural activation in age- and habitual exercise-related
      differences in the thermic effect of food.
AB  - The thermic effect of food (TEF) declines with advancing age in adult humans but
      is enhanced in the habitually exercising state. The responsiveness of the
      sympathetic nervous system (SNS) has been implicated in these differences in TEF.
      We tested the hypotheses that 1) the reduction in TEF with aging is associated
      with an attenuated SNS response to acute energy intake; and 2) the greater TEF
      observed in endurance exercise-trained adults is associated with an augmented SNS
      response. Four groups of healthy men were studied: 16 young and 11 older
      sedentary men and nine young and 10 older habitually exercising men. Metabolic
      rate (indirect calorimetry, ventilated hood), skeletal muscle sympathetic nerve
      activity (MSNA; peroneal microneurography), and plasma norepinephrine and plasma
      epinephrine concentrations were measured before and for up to 4 h after ingestion
      of a carbohydrate drink (2.5 g/kg fat-free mass). TEF was approximately 50%
      greater in young compared with older men (P < 0.05) and approximately 25% greater
      in exercising compared with sedentary men (P < 0.05). In contrast, the MSNA,
      plasma norepinephrine, and plasma epinephrine responses were not different among
      the four groups. Covarying for MSNA did not significantly alter the observed
      differences in TEF. Habitual exercise status did not affect the age-associated
      decline in TEF. These findings demonstrate that altered postprandial whole-body
      and skeletal muscle SNS activation is not an important mechanism mediating either
      the reduction in TEF with aging or the augmented TEF associated with the exercise
      trained state in healthy men. Differences in beta-adrenergic responsiveness to
      postprandial sympathoadrenal stimulation and/or nonsympathetic adrenergic
      influences likely explain the age- and habitual exercise-related differences in
      TEF.

PMID- 15472219
TI  - Estrogen abrogates transcervical tight junctional resistance by acceleration of
      occludin modulation.
AB  - The present study explored the effects of estrogen on transcervical tight
      junctional resistance (R(TJ)) and the mechanisms involved. Treatment of cultured
      human cervical epithelial cells with 17beta-estradiol decreased in a time- and
      dose-related manner the R(TJ). Estrogen had no significant effect on the
      expression of E-Cadherin, zonula-occluden-1, or Claudin-4. In contrast, 17beta
      estradiol modulated expression of the transmembrane tight-junctional protein
      occludin: at low concentrations (1 and 10 nm) estradiol increased the density of
      occludin 65-kDa form but at the higher concentration of 100 nm estradiol induced
      only a mild 2-fold increase in the density of this form. Estradiol also increased
      the expression of occludin 50-kDa form in a dose-related manner. The R(TJ) and
      occludin effects of estradiol were reversible and could be blocked by tamoxifen
      but not progesterone. The present results rule out estrogen modulation of
      occludin transcription. In contrast, the results suggest that the occludin
      effects of estrogen involve posttranslational up-regulation of occludin turnover,
      including synthesis and degradation. The effects of estrogen on occludin
      expression were compared with those of proteinase-K, plasmin, and matrix
      metaloproteinase-2 (all added extracellularly). The three proteinases abrogated
      irreversibly the R(TJ) and induced expression de novo of occludin low-molecular
      weight forms. The latter, however, differed from the effect of estrogen, which
      generated only a single 50-kDa form. Collectively, the present data suggest that
      the occludin 50-kDa form is an estrogen-specific-induced occludin isoform and
      that the mechanism of estrogen-abrogation of transcervical R(TJ) involves
      occludin modulation.

PMID- 15472220
TI  - Cartilage oligomeric matrix protein increases in serum after the start of growth
      hormone treatment in prepubertal children.
AB  - Both GH and IGF-I stimulate bone growth, but the molecular mechanisms mediating
      their effects on the growth plate are not fully understood. We measured gene
      expression by microarray analysis in primary cultured human chondrocytes treated
      with either GH or IGF-I. One of the genes found to be up-regulated by both GH and
      IGF-I was that encoding cartilage oligomeric matrix protein (COMP). This protein
      is predominantly found in the extracellular matrix of cartilage. Mutations in the
      COMP gene have been associated with syndromes of short stature. To verify that
      COMP is regulated by GH in vivo, we measured COMP levels in serum in short
      children treated with GH. The study included 113 short prepubertal children (14
      girls and 99 boys) with a mean (+/- sd) age of 8.84 +/- 2.76 yr, height sd score
      of -2.74 +/- 0.67, and IGF-I sd score of -1.21 +/- 1.07 at the start of GH
      administration. Serum levels of COMP were 1.58 +/- 0.28, 1.83 +/- 0.28 (P <
      0.0001), 1.91 +/- 0.28 (P < 0.0001), 1.78 +/- 0.28 (P < 0.001), and 1.70 +/- 0.24
      (P < 0.05) microg/ml at baseline and after 1 wk and 1, 3, and 12 months,
      respectively. In conclusion, we have demonstrated that COMP expression is up
      regulated by both GH and IGF-I in primary cultured human chondrocytes.
      Furthermore, serum levels of COMP increase after the start of GH treatment in
      short children.

PMID- 15472221
TI  - Leydig cell hypoplasia: absent luteinizing hormone receptor cell surface
      expression caused by a novel homozygous mutation in the extracellular domain.
AB  - Leydig cell hypoplasia is a rare autosomal recessive condition that interferes
      with normal development of male external genitalia in 46,XY individuals. We have
      studied a family with a 46,XY girl due to a new homozygous mutation (V144F) in
      the extracellular ligand-binding domain. HEK 293 cells transfected with the
      mutant LH receptor exhibited a marked impairment of human chorionic gonadotropin
      binding. Using Western blotting of the expressed V144F mutant LH receptor protein
      showed the absence of the glycosylated cell surface form. Treatment of the mutant
      LH receptor with N-glycosidase F or endoglycosidase-H demonstrated that the
      mutant receptor is retained in the endoplasmic reticulum. Expression and study of
      enhanced green fluorescent protein-tagged receptors confirmed that the mutant LHR
      V144F receptors do not migrate to the cell surface, and the fluorescence remains
      intracellular and colocalizes with an endoplasmic reticulum marker, ER-tracker
      Blue-white DPX. Comparison of the theoretical molecular models of the
      extracellular domain of the wild-type and the mutant receptor suggests that the
      mutation LHR-V144F, located in the outer circumference in a alpha-helix of the
      leucine-rich repeat 4, may induce a conformational strain on the molecule. F144
      of the mutant LH receptor has overlapping interactions with F119, which V144 in
      the wild-type receptor has not.

PMID- 15472222
TI  - Characterization of the endocannabinoid system in early human pregnancy.
AB  - In recent years, it has been demonstrated that high circulating levels of the
      endogenous cannabinoid anandamide, resulting from low expression of its
      metabolizing enzyme fatty acid amide hydrolase (FAAH), may contribute to
      spontaneous miscarriage and poor outcome in women undergoing in vitro
      fertilization. The site of action of this compound, however, has not been
      determined. In this study, we examined the distribution of the cannabinoid
      receptors, CB1 and CB2, and the endocannabinoid-metabolizing enzyme FAAH in first
      trimester human placenta. Here, we show that FAAH is expressed throughout the
      human first trimester placenta, in extravillous trophoblast columns, villous
      cytotrophoblasts, syncytiotrophoblasts, and macrophages. Furthermore, FAAH mRNA
      levels appear to be regulated during gestation, with levels peaking at 11 wk
      before declining again. The immune system-associated cannabinoid CB2 receptors
      were localized only to placental macrophages. Interestingly, the cannabinoid
      receptor CB1 was not identified in first trimester placenta despite having
      previously been shown to be present in placental tissues at term. These findings
      suggest that the placenta may form a barrier preventing maternal-fetal transfer
      of anandamide and/or modulate local levels of anandamide by regulation of FAAH
      expression with gestation.

PMID- 15472223
TI  - Analysis of BRAF point mutation and RET/PTC rearrangement refines the fine-needle
      aspiration diagnosis of papillary thyroid carcinoma.
AB  - Point mutations in BRAF are genetic hallmarks of papillary thyroid carcinoma
      (PTC). In this retrospective study, we examined thyroid aspirates and
      corresponding paraffin-embedded surgical samples for the presence of BRAF
      mutations. Altogether, we examined 96 cases, including 69 PTCs, 19 follicular
      adenomas, and eight nontoxic nodular goiters for BRAF; 60 of these samples were
      also examined for RET/PTC rearrangements. The results were correlated with the
      cytological diagnosis and the final histopathology. The BRAF mutation (V599E) was
      detected in 38% of the samples that were PTC on histopathology; RET/PTC was found
      in 18% of the PTC cases. In all the cases, the presence of the genetic alteration
      was confirmed in the surgically resected tumor. The identification of BRAF
      mutation and RET/PTC refined the diagnosis of PTC in five of 15 samples that were
      considered either indeterminate or insufficient at cytology. No mutation was
      found in aspirates of follicular adenomas and nontoxic nodular goiters. These
      results indicate that BRAF mutation and RET/PTC rearrangements are molecular
      markers of PTC that can be applied to FNA in adjunct to traditional cytology.

PMID- 15472224
TI  - Evidence for differential effects of selective somatostatin receptor subtype
      agonists on alpha-subunit and chromogranin a secretion and on cell viability in
      human nonfunctioning pituitary adenomas in vitro.
AB  - Somatostatin (SRIF) analogs interacting with SRIF receptor (SSTR) subtypes SSTR2
      and SSTR5 reduce hormone secretion of pituitary adenomas, but their
      antiproliferative effects are still controversial. We investigated the in vitro
      effects of SRIF and SSTR-selective agonists interacting with SSTR1 (BIM-23926),
      SSTR2 (BIM-23120), SSTR5 (BIM-23206), or both SSTR2 and SSTR5 (BIM-23244) on
      alpha-subunit and chromogranin A secretion and on cell viability of 12
      nonfunctioning pituitary adenomas (NFA) expressing SSTR1, SSTR2, and SSTR5, as
      assessed by RT-PCR. Treatment with SRIF or BIM-23206 did not modify alpha-subunit
      and chromogranin A secretion, which was significantly inhibited by BIM-23926, BIM
      23120, and BIM-23244. SRIF and BIM-23120 did not influence cell viability, which
      was significantly promoted by BIM-23206 and BIM-23244 and reduced by treatment
      with BIM-23926. These results demonstrate that, in the selected NFA, the SSTR1
      selective agonist inhibits secretory activity and cell viability, the SSTR2
      selective agonist inhibits secretion but not cell viability, and the SSTR5
      selective agonist does not influence secretion but promotes cell viability. These
      data can explain the lack of inhibitory effects of currently used SRIF analogs
      and suggest that drugs acting potently and preferentially on SSTR1 might be
      useful for medical treatment of NFA.

PMID- 15472225
TI  - Adenosine 5'-triphosphate activates nuclear translocation of mitogen-activated
      protein kinases leading to the induction of early growth response 1 and raf
      expression in human granulosa-luteal cells.
AB  - With the stimulation of many types of cell surface receptors, MAPKs are
      activated. We have previously demonstrated an effect of extracellular ATP on ERKs
      and gonadotropin- induced progesterone secretion, implicating the significance of
      ATP in the regulation of ovarian function. However, little is known about the
      specific role of ATP in the subsequent MAPK-induced signaling cascade in human
      granulosa-luteal cells (hGLCs). The present study was designed to examine the
      effect of ATP on the activation of the MAPK signaling pathway, including nuclear
      translocation and the expression of the immediate early genes in hGLCs. Western
      blot analysis, using a monoclonal antibody, which detected the total and
      phosphorylated forms of ERK1 and ERK2 (p42(mapk) and p44 (mapk), respectively),
      demonstrated that exogenous ATP evoked ERKs in a dose- and time-dependent manner.
      In contrast, p38 and JNK were not significantly activated after ATP treatment. To
      examine the translocation of activated ERKs, fluorescein isothiocyanate
      conjugated secondary antibody was used to detect the distribution of total and
      phosphorylated ERKs. Immunofluorescent staining revealed that phosphorylated ERKs
      were translocated from cytoplasm into nucleus subsequent to 10 microm ATP
      treatment. To study the gene(s) induced by exogenous ATP, mRNA was extracted from
      hGLCs in the presence or absence of 10 microm ATP. Gene array for 23 genes
      associated with members of the mitogenic pathway cascade and immediate early
      genes revealed that the expression of early growth response 1 and c-raf-1 was
      increased. To our knowledge, this is the first demonstration of the ATP-induced
      nuclear translocation of MAPKs in the human ovary. These results suggest that the
      MAPK signaling pathway plays a role in mediating ATP actions in the human ovary.

PMID- 15472226
TI  - Signaling through 3',5'-cyclic adenosine monophosphate and phosphoinositide-3
      kinase induces sodium/iodide symporter expression in breast cancer.
AB  - The sodium/iodide symporter (NIS) is a membrane transport glycoprotein normally
      expressed in the thyroid gland and lactating mammary gland. NIS is a target for
      radioiodide imaging and therapeutic ablation of thyroid carcinomas and has the
      potential for similar use in breast cancer treatment. To facilitate NIS-mediated
      radionuclide therapy, it is necessary to identify signaling pathways that lead to
      increased NIS expression and function in breast cancer. We examined NIS
      expression in mammary tumors of 14 genetically engineered mouse models to
      identify genetic manipulations associated with NIS induction. The cAMP and
      phosphoinositide-3 kinase (PI3K) signaling pathways are associated with NIS up
      regulation. We showed that activation of PI3K alone is sufficient to increase NIS
      expression and radioiodide uptake in MCF-7 human breast cancer cells, whereas
      cAMP stimulation increases NIS promoter activity and NIS mRNA levels but is not
      sufficient to increase radioiodide uptake. This study is the first to demonstrate
      that NIS expression is induced by cAMP and/or PI3K in breast cancer both in vivo
      and in vitro.

PMID- 15472227
TI  - Long-acting follicle-stimulating hormone analogs containing N-linked
      glycosylation exhibited increased bioactivity compared with o-linked analogs in
      female rats.
AB  - The effects of altering the number and type of additional carbohydrate moieties
      on the pharmacokinetic and pharmacodynamic properties of FSH were examined in
      this report. A series of single-chain follitropins, containing variable numbers
      of additional N- (or O-) linked carbohydrates, were designed and expressed in
      Chinese hamster ovary cells. Proper folding, efficient receptor binding, and
      signal transduction were confirmed by in vitro assays. Pharmacokinetic and
      pharmacodynamic parameters were evaluated in immature female Sprague Dawley rats.
      Increasing the number of glycosylation sites with either N- (or O-) linked
      moieties extended the elimination half-life as much as 2-fold compared with
      recombinant human FSH (rhFSH). However, there was a maximum elimination half-life
      such that further glycosylation provided no additional lengthening of the half
      life. Conversely, biopotency, as assessed by inhibin A levels 74 h post
      injection, and follicle production were significantly higher for the N-linked
      analogs. Rats stimulated with the longest acting analogs (either N- or O-linked)
      showed significantly higher ovarian weights than rats receiving a single
      injection of rhFSH. The analog containing four additional N-linked sites (rhFSH
      N4) had the greatest number of large, preovulatory follicles. Although the half
      life of rhFSH-N4 displayed no further enhancement beyond the other longest acting
      analogs, this analog exhibited significantly increased biopotency in rats. This
      work provides the basis for the generation of a series of reagents potentially
      useful for therapeutic applications.

PMID- 15472228
TI  - Effects of 3,5,3'-triiodothyronine on the invasive potential and the expression
      of integrins and matrix metalloproteinases in cultured early placental
      extravillous trophoblasts.
AB  - It is well known that T(3) plays a crucial role in the maintenance of early
      pregnancy through the induction of endocrine function in villous trophoblasts.
      The effects of T(3) on extravillous trophoblast (EVT) function, however, remain
      to be elucidated. To investigate the possible role of T(3) in the regulation of
      EVT invasion to the decidua, we have examined whether T(3) affects EVT invasive
      potential and the expression of matrix metalloproteinase-2 (MMP-2), MMP-3, tissue
      inhibitor metalloproteinase-1, fetal fibronectin (FN), and integrin
      alpha(5)beta(1) in cultured early placental EVTs. Isolation and purification of
      trophoblasts differentiating into EVTs were performed by the enzymatic digestion
      of the anchoring chorionic villi, with the use of human FN-precoated culture
      dishes and FN-precoated Matrigel Transwells. The cells attached to the dishes
      were subcultured in DMEM supplemented with 10% fetal bovine serum for 48 h and
      were characterized by RT-PCR analysis after 24-h subculture and
      immunocytochemical analysis after 48-h subculture for specific EVT markers.
      Thereafter, the cultured cells were stepped down to a 4% fetal bovine serum
      condition and cultured in the presence or absence of T(3) (10(-8) m) for the
      subsequent 72 h. Matrigel invasion assay demonstrated that the treatment with
      T(3) significantly increased the number of cell projections of subsequent 24-, 48
      , and 72-h cultured EVTs. RT-PCR analysis revealed that the treatment with T(3)
      increased the expression of MMP-2, MMP-3, fetal FN, and integrin alpha(5)beta(1)
      mRNA in subsequent 24-h cultured EVTs compared with those in control cultures.
      Immunocytochemical and Western immunoblot analyses revealed that treatment with
      T(3) increased the expression of MMP-2 and MMP-3 in subsequent 48-h cultured EVTs
      compared with those in control cultures. The present results suggest that T(3)
      (10(-8) m) may play a vital role in up-regulating the invasive potential of EVTs
      into the decidua.

PMID- 15472229
TI  - Specificity and regioselectivity of the conjugation of estradiol, estrone, and
      their catecholestrogen and methoxyestrogen metabolites by human uridine diphospho
      glucuronosyltransferases expressed in endometrium.
AB  - Uridine diphospho-glucuronosyltransferases (UGTs) inactivate and facilitate the
      excretion of estrogens to glucuronides (-G), the most abundant circulating
      estrogen conjugates. The identity of the conjugated estrogens formed by all known
      overexpressed UGTs (n = 16) was analyzed by comparison with retention time and
      mass fragmentation of authentic standards by HPLC tandem mass spectrometry
      methods. Six UGTs, namely 1A1, 1A3, 1A8, 1A9, 1A10, and 2B7, were found to
      glucuronidate estradiol (E(2)) and estrone (E(1)), their hydroxyls (OH), and
      their methoxy derivatives (MeO). Addition of glucuronic acid was catalyzed by
      specific UGTs at positions 2, 3, and 4 of the estrogens, whereas only E(2) was
      conjugated at position 17 by UGT2B7. Kinetic parameters indicate that the
      conjugation of E(2) at position 3 was predominantly catalyzed by 1A1, 1A3, and
      1A8 and by 1A8 for E(1). Conjugation of 2-OHE(1)/E(2) and 2- and 4-MeOE(1)/E(2)
      was selective at position 3, mostly catalyzed by 1A1 and 1A8. Of all UGTs, UGT2B7
      demonstrated the highest catalytic activities for estrogens and at least 10- to
      50-fold higher activity for the conjugation of genotoxic 4
      hydroxycatecholestrogens at position 4, compared with the conjugation of E(2),
      E(1), and 2-hydroxycatecholestrogens. Its presence was further shown in the
      endometrium by RT-PCR and immunohistochemistry, localizing in the same cells
      expressing CYP1B1, involved locally in the formation of 4
      hydroxycatecholestrogens. Data show that several UGT enzymes detected in the
      endometrium are involved in the glucuronidation of E(2) and its 2-OH, 4-OH, and 2
      MeO metabolites that exert various biological effects in the tissue.

PMID- 15472230
TI  - Wild-type p53 protein is up-regulated upon cyclic adenosine monophosphate-induced
      differentiation of human endometrial stromal cells.
AB  - Decidualization of the endometrial stromal compartment is critical for embryo
      implantation. Initiation of this differentiation process requires elevated
      intracellular cAMP levels. We now report a massive and sustained up-regulation of
      p53 tumor suppressor protein during cAMP-induced decidualization of cultured
      endometrial stromal cells. Nuclear accumulation of p53 was not accompanied by
      increased mRNA expression, suggesting stabilization of the protein as the
      underlying mechanism. Proteasomal degradation of p53 is known to be mediated by
      nuclear Mdm2. Nuclear translocation of Mdm2, in turn, is dependent on
      phosphorylation by protein kinase B/Akt (PKB/Akt). In cAMP-treated decidualized
      cells, p53 accumulation was associated with decreased nuclear Mdm2 and
      cytoplasmic PKB/Akt levels. Conversely, withdrawal of the decidualization
      stimulus resulted in morphological and biochemical dedifferentiation,
      disappearance of p53, but increased abundance of PKB/Akt. Furthermore, Western
      blot and immunohistochemical analyses of endometrial biopsies confirmed that p53
      is expressed in vivo in the stromal compartment during the late secretory phase
      of the cycle. The observation that p53 protein expression is closely associated
      with decidual transformation indicates a novel role for this tumor suppressor in
      regulating human endometrial function.

PMID- 15472231
TI  - Androgen receptor in human skeletal muscle and cultured muscle satellite cells:
      up-regulation by androgen treatment.
AB  - Androgens stimulate myogenesis, but we do not know what cell types within human
      skeletal muscle express the androgen receptor (AR) protein and are the target of
      androgen action. Because testosterone promotes the commitment of pluripotent,
      mesenchymal cells into myogenic lineage, we hypothesized that AR would be
      expressed in mesenchymal precursor cells in the skeletal muscle. AR expression
      was evaluated by immunohistochemical staining, confocal immunofluorescence, and
      immunoelectron microscopy in sections of vastus lateralis from healthy men before
      and after treatment with a supraphysiological dose of testosterone enanthate.
      Satellite cell cultures from human skeletal muscle were also tested for AR
      expression. AR protein was expressed predominantly in satellite cells, identified
      by their location outside sarcolemma and inside basal lamina, and by CD34 and C
      met staining. Many myonuclei in muscle fibers also demonstrated AR
      immunostaining. Additionally, CD34+ stem cells in the interstitium, fibroblasts,
      and mast cells expressed AR immunoreactivity. AR expression was also observed in
      vascular endothelial and smooth muscle cells. Immunoelectron microscopy revealed
      aggregation of immunogold particles in nucleoli of satellite cells and myonuclei;
      testosterone treatment increased nucleolar AR density. In enriched cultures of
      human satellite cells, more than 95% of cells stained for CD34 and C-met,
      confirming their identity as satellite cells, and expressed AR protein. AR mRNA
      and protein expression in satellite cell cultures was confirmed by RT-PCR,
      reverse transcription and real-time PCR, sequencing of RT-PCR product, and
      Western blot analysis. Incubation of satellite cell cultures with
      supraphysiological testosterone and dihydrotestosterone concentrations (100 nm
      testosterone and 30 nm dihydrotestosterone) modestly increased AR protein levels.
      We conclude that AR is expressed in several cell types in human skeletal muscle,
      including satellite cells, fibroblasts, CD34+ precursor cells, vascular
      endothelial, smooth muscle cells, and mast cells. Satellite cells are the
      predominant site of AR expression. These observations support the hypothesis that
      androgens increase muscle mass in part by acting on several cell types to
      regulate the differentiation of mesenchymal precursor cells in the skeletal
      muscle.

PMID- 15472232
TI  - PROP1 mutations cause progressive deterioration of anterior pituitary function
      including adrenal insufficiency: a longitudinal analysis.
AB  - Mutations in the PROP1 gene are the most frequent genetic defects in patients
      with combined pituitary hormone insufficiency. However, controversy exists about
      the timing and extent of pituitary insufficiency, and it remains unclear whether
      adrenal failure is a typical feature of this condition. We performed a
      retrospective longitudinal analysis of nine patients with PROP1 mutations who
      were under medical supervision at our clinic for 15.7 +/- 3.4 yr. All patients
      initially presented with growth failure (height sd score, -3.7 +/- 0.3) at a mean
      age of 4.9 +/- 0.8 yr. They were first diagnosed with GH and TSH deficiency, and
      replacement therapy was instituted at 6.1 +/- 1.1 and 6.8 +/- 1.2 yr,
      respectively. All seven patients who reached pubertal age required sex hormone
      substitution at 15.0 +/- 0.7 yr. Repeated functional testing of the anterior
      pituitary axes revealed a progressive decline with age in peak levels of GH, TSH,
      prolactin, and LH/FSH. All patients developed at least partial adrenal
      insufficiency, with a gradual decline of the function of the pituitary adrenal
      axis and eventually required substitution with hydrocortisone at a mean age of
      18.4 +/- 3.5 yr. It is concluded that anterior pituitary function in patients
      with PROP1 mutations deteriorates progressively and includes adrenal
      insufficiency as a feature of this condition, which has important clinical
      relevance in childhood and adolescence.

PMID- 15472233
TI  - Distinct idiotypes of insulin autoantibody in autoimmune polyendocrine syndrome
      type 2 and childhood onset type 1 diabetes.
AB  - Insulin autoantibodies (IAA) are present in type 1 diabetes (T1D) and other
      autoimmune diseases. The differences in the IAA epitopes in various clinical
      diseases have not been evaluated. We used phage display to select phagotopes
      specific to IAA from a newly diagnosed T1D child (designated FPP) and from an
      adult-onset T1D subject with autoimmune polyendocrine syndrome type 2 (APS-II).
      The phagotopes randomly selected were tested as antiidiotope reagents to displace
      human radiolabeled insulin in the microfiltration radiobinding assay using IAA(+)
      sera from T1D subjects and insulin antibody (IA(+)) sera from insulin-treated
      type 2 diabetes subjects. The DNA of the phagotopes selected from the FPP and APS
      sera revealed consensus amino acid sequences of GRG and LGKRS, respectively.
      Phagotope FPP-10 displaced insulin binding in 90% of IAA(+) subjects but not in
      the IA(+) or the APS subject. Phagotope APS-4 was able to displace insulin
      binding from the APS subject but not in the IAA(+) or IA(+) subjects. We have
      demonstrated antiidiotope reagents able to distinguish childhood-onset T1D
      associated IAA(+) from adult-onset T1D (APS-II-associated IAA(+)) that are
      different from their specificity for human insulin and from its antiidiotope
      amino acid sequence.

PMID- 15472234
TI  - Is growth hormone treatment in young children safe for the heart?

PMID- 15472235
TI  - Low plasma bicarbonate level in hyponatremia related to adrenocorticotropin
      deficiency.

PMID- 15472236
TI  - Selective serotonin reuptake inhibitors.

PMID- 15472237
TI  - Why the GMC is right to appeal over life prolonging treatment.

PMID- 15472238
TI  - Antenatal screening for Down's syndrome.

PMID- 15472239
TI  - Managing metastatic bone pain.

PMID- 15472240
TI  - Publishing tobacco tar measurements on packets.

PMID- 15472242
TI  - GMC decision on Southall is challenged as "unduly lenient".

PMID- 15472243
TI  - Scientists receive Nobel prize for unravelling secrets of smell.

PMID- 15472244
TI  - FDA to review risks of antidepressants in adults.

PMID- 15472245
TI  - Merck withdraws arthritis drug worldwide.

PMID- 15472251
TI  - Less than half the world is likely to meet target for cutting child deaths.

PMID- 15472249
TI  - European Commission wants drug companies to test products for use in children.

PMID- 15472253
TI  - A quarter of young children in Iraq are chronically malnourished.

PMID- 15472255
TI  - US accrediting agency tightens rules for continuing medical education.

PMID- 15472258
TI  - US Justice Department appeals against the rulings that banning partial birth
      abortion is unconstitutional.

PMID- 15472259
TI  - Scottish researchers apply for licence for human cloning.

PMID- 15472261
TI  - Women sue over epilepsy drug risks.

PMID- 15472262
TI  - McDonald's profits drop and Mars abandons king size bars.

PMID- 15472264
TI  - Paediatric cardiac surgical mortality in England after Bristol: descriptive
      analysis of hospital episode statistics 1991-2002.
AB  - OBJECTIVE: To describe trends in mortality of open cardiac surgery in children in
      Bristol and England since 1991. DESIGN: Retrospective analysis of hospital
      episode statistics data. SETTING: All open cardiac surgery of children in
      England. POPULATION: Patients younger than 16 undergoing open cardiac surgical
      procedures in England between April 1991 and March 2002. Three time periods were
      defined: epoch 3 (April 1991 to March 1995), epoch 5 (April 1996 to March 1999),
      epoch 6 (April 1999 to March 2002). MAIN OUTCOME MEASURE: Mortality in hospital
      within 30 days of a cardiac procedure. RESULTS: We identified 5221 open
      operations between April 1996 and March 2002 in children under 1 year and 6385 in
      children aged 1-15 years. Mortality for all centres combined fell from 12% in
      epoch 3 to 4% in epoch 6. Mortality in children under 1 year at Bristol fell from
      29% (95% confidence interval 21% to 37%) in epoch 3 to 3% (1% to 6%) in epoch 6,
      below the national average. The reduction in mortality did not seem to be due to
      fewer high risk procedures or an increase in the numbers of low risk cases.
      Oxford had a significantly higher mortality than the national average in all
      three epochs (11% (5% to 18%) in epoch 6), which was not affected by adjusting
      for procedure or the inclusion of cases with missing outcomes. CONCLUSIONS: At
      Bristol, mortality for open operations in children aged under 1 year has fallen
      markedly, to below the national average. Nationwide mortality has also fallen.
      Improved quality of care may account for the drop in mortality, through new
      technologies or improved perioperative and postoperative care, or both.

PMID- 15472265
TI  - What can experience add to early medical education? Consensus survey.
AB  - OBJECTIVE: To provide a rationale for integrating experience into early medical
      education ("early experience"). DESIGN: Small group discussions to obtain
      stakeholders' views. Grounded theory analysis with respondent, internal, and
      external validation. SETTING: Problem based, undergraduate medical curriculum
      that is not vertically integrated. PARTICIPANTS: A purposive sample of 64
      students, staff, and curriculum leaders from three university medical schools in
      the United Kingdom. RESULTS: Without early experience, the curriculum was
      socially isolating and divorced from clinical practice. The abruptness of
      students' transition to the clinical environment in year 3 generated positive and
      negative emotions. The rationale for early experience would be to ease the
      transition; orientate the curriculum towards the social context of practice; make
      students more confident to approach patients; motivate them; increase their
      awareness of themselves and others; strengthen, deepen, and contextualise their
      theoretical knowledge; teach intellectual skills; strengthen learning of
      behavioural and social sciences; and teach them about the role of health
      professionals. CONCLUSION: A rationale for early experience would be to
      strengthen and deepen cognitively, broaden affectively, contextualise, and
      integrate medical education. This is partly a process of professional
      socialisation that should start earlier to avoid an abrupt transition.
      "Experience" can be defined as "authentic human contact in a social or clinical
      context that enhances learning of health, illness or disease, and the role of the
      health professional."

PMID- 15472267
TI  - Recent developments and current status of gene therapy using viral vectors in the
      United Kingdom.

PMID- 15472268
TI  - Mucocutaneous leishmaniasis: an imported infection among travellers to central
      and South America.

PMID- 15472269
TI  - Immediate care of the preterm infant.

PMID- 15472270
TI  - Informed consent and communication of risk from radiological and nuclear medicine
      examinations: how to escape from a communication inferno.

PMID- 15472271
TI  - Making clinical decisions when the stakes are high and the evidence unclear.

PMID- 15472272
TI  - Improving mortality of coronary surgery: data analysis was not robust.

PMID- 15472273
TI  - Improving mortality of coronary surgery: study conclusions are paradoxical.

PMID- 15472274
TI  - Adverse events reporting in English hospital statistics: no data were produced.

PMID- 15472275
TI  - Adverse events reporting in English hospital statistics: vague numbers are being
      perpetuated.

PMID- 15472276
TI  - Bypass surgery mortality is blunt measure of performance.

PMID- 15472277
TI  - Performance monitoring should take costs to heart.

PMID- 15472278
TI  - The prince and the professor: integrated approach is needed.

PMID- 15472279
TI  - Adverse events reporting in English hospital statistics: patients should be
      involved as partners.

PMID- 15472280
TI  - Adverse events reporting in English hospital statistics: data relevant to patient
      safety should not be presented alone and out of context.

PMID- 15472281
TI  - The prince and the professor: With respect, professor, the Prince of Wales is not
      so wrong.

PMID- 15472282
TI  - The prince and the professor: With respect, Professor Baum, you've got it wrong.

PMID- 15472283
TI  - The prince and the professor: Which emperor is naked?

PMID- 15472284
TI  - Human touch could be saved by using robots.

PMID- 15472286
TI  - The prince and the professor: Science is worth the effort.

PMID- 15472288
TI  - Rare and emerging opportunistic fungal pathogens: concern for resistance beyond
      Candida albicans and Aspergillus fumigatus.

PMID- 15472289
TI  - Microscopic observation drug susceptibility assay, a rapid, reliable diagnostic
      test for multidrug-resistant tuberculosis suitable for use in resource-poor
      settings.
AB  - There is an urgent need for new tools to improve our ability to diagnose
      tuberculosis (TB) and multidrug-resistant TB (MDR-TB) in resource-poor settings.
      In a retrospective analysis undertaken in a region with a high incidence of TB,
      we evaluated the performance of the microscopic observation drug susceptibility
      assay (MODS), a novel assay developed in Peru which uses an inverted light
      microscope and culture in Middlebrook 7H9 broth to detect mycobacterial growth.
      MODS detected 94.0% of 1,908 positive sputum cultures, whereas Lowenstein-Jensen
      (LJ) culture detected only 86.9% (P < 0.001). The median time to culture
      positivity was 8 days (compared to 16 days for the same 208 samples by LJ
      culture; P < 0.001, Wilcoxon signed rank test). The results obtained by direct
      susceptibility testing using MODS demonstrated excellent concordance for
      isoniazid and rifampin and the detection of multidrug resistance with those
      obtained by indirect colorimetric methods: the microplate Alamar Blue assay
      (MABA) and the tetrazolium microplate assay (TEMA) (agreement, 95, 98, and 94%;
      kappa values, 0.8, 0.7, and 0.7, respectively). The concordance of the
      susceptibility testing results for ethambutol and streptomycin was poor. MODS is
      a novel assay which can detect the organisms responsible for TB and MDR-TB
      directly from sputum inexpensively, rapidly, and effectively. A comprehensive
      prospective evaluation of MODS is under way in Peru, and independent validation
      in nonresearch laboratories should be undertaken at the earliest opportunity.

PMID- 15472290
TI  - Direct detection of rifampin-resistant mycobacterium tuberculosis in respiratory
      specimens by PCR-DNA sequencing.
AB  - This study evaluated the feasibility of a molecular strategy based on
      identification of Mycobacterium tuberculosis by IS6110 PCR or Cobas Amplicor PCR,
      and rpoB PCR-DNA sequencing of the 81-bp rifampin resistance determining region
      (RRDR) for direct detection of rifampin resistance in respiratory specimens. A
      collection of 2,138 respiratory specimens and 352 nonduplicate M. tuberculosis
      isolates (including 233 isolates from the evaluated respiratory specimens and an
      additional collection of 119 stored isolates) from Southern China was
      investigated. Using culture as the reference test, the overall diagnostic
      sensitivities of an acid-fast bacillus (AFB) smear, Cobas Amplicor PCR, IS6110
      PCR were 54.5% (156 of 286), 86.7% (248 of 286), and 89.2% (255 of 286),
      respectively. The sensitivities of the rpoB PCR for the specimens with positive
      AFB smears and with positive PCR results in the IS6110 PCR and/or Cobas Amplicor
      PCR were 100% (156 of 156) and 92.3% (239 of 259), respectively. Of the 352
      nonduplicate M. tuberculosis isolates, the agar proportion method for rifampin
      reported 39 resistant strains. Full agreement (352 of 352) was found with the
      agar proportion method and the genotype inferred from the rpoB DNA sequencing
      data for rifampin. Thirty-nine mutations of nine distinct kinds, eight point
      mutations, and one deletion within the RRDR were found in the 39 resistant
      strains. For the direct DNA sequencing performed on rpoB PCR-positive respiratory
      specimens, the concordance with the agar proportion method and the subsequent PCR
      sequencing for the culture isolate was 100%. This strategy has potential
      application for direct and rapid diagnosis of rifampin-resistant M. tuberculosis
      in IS6110 PCR or Cobas Amplicor PCR-positive respiratory specimens.

PMID- 15472291
TI  - Origins of microsatellite diversity in the Trichophyton rubrum-T. violaceum clade
      (Dermatophytes).
AB  - We analyzed the population structure of the anthropophilic dermatophyte species
      Trichophyton violaceum, which mainly causes tinea capitis, and T. rubrum, the
      most frequently isolated agent of dermatophytosis worldwide. A microsatellite
      marker (T1) was developed by using the enrichment technique for microsatellites.
      The T1 marker containing a (GT)(8-10) repeat was proven to specifically amplify
      both species, underlining their close kinship. Four polymorphic alleles were
      detected within a set of about 130 strains by using polyacrylamide gel
      electrophoresis with this marker. An association with geographic origin of the
      isolates was apparent. Given the close relatedness of both species, these data
      suggest an African origin of the entire T. rubrum complex, followed by the
      emergence of a new genotype (B) in Asia with subsequent spread of this genotype
      over Europe and the United States.

PMID- 15472292
TI  - Serotypes and sequence types of pneumococci causing invasive disease in Scotland
      prior to the introduction of pneumococcal conjugate polysaccharide vaccines.
AB  - Pneumococcal conjugate polysaccharide (Pnc) vaccines are now available, and the
      need for an improved understanding of circulating pneumococcal serotypes and
      sequence types (STs) is recognized. Three hundred sixty-eight pneumococci
      isolated in cases of invasive disease in Scotland in the first 6 months of 2003
      were analyzed. The isolates belonged to 30 serotypes, and there was a strong
      correlation between serotype and ST, although only nine serotypes consisted of a
      single ST. The following serotypes coexisted with the following numbers of STs:
      serotype 14, 10 STs, serotype 8, 8 STs; serotype 4, 6 STs; serotype 22F, 8 STs;
      serotype 9V, 7 STs; serotype 23F, 6 STs; serotype 6B, 6 STs; serotype 1, 3 STs;
      serotype 3, 3 STs; and serotype 7F, 3 STs. Our data also showed a strong
      association between ST and serotype, although 19 STs contained multiple
      serotypes. Of the 10 most common STs, 6 coexisted with a single serotype each.
      Vaccine coverage in all age groups was 94.9% for the 23-valent polysaccharide
      vaccine and 50.7, 55.4, and 64.1% for the 7-, 9-, and 11-valent Pnc vaccines,
      respectively. For those under the age of 2 years, 79% coverage would be provided
      by the 7-, 9-, and 11-valent Pnc vaccines.

PMID- 15472293
TI  - Detection of U.S., Lelystad, and European-like porcine reproductive and
      respiratory syndrome viruses and relative quantitation in boar semen and serum
      samples by real-time PCR.
AB  - Transmission of porcine reproductive and respiratory syndrome virus (PRRSV) via
      boar semen has been documented. Since semen is widely disseminated for artificial
      insemination and the virus can cause significant health and economic
      consequences, it is essential to have well-validated, rapid diagnostic techniques
      to detect and quantitate the virus for diagnostic and research purposes.
      Previously, boar semen was tested by a nested PCR (nPCR) assay which was compared
      to the "gold standard" swine bioassay. A correlation of 94% was observed,
      indicating that, most of the time, PCR detected infectious virus. Subsequently, a
      real-time PCR targeting the 3' untranslated region of the PRRSV genome was
      compared with nPCR by testing 413 serum and semen samples from PRRSV-inoculated
      and control boars. There was 95% agreement between the results of the two tests,
      with the majority of samples with discordant results containing virus at the
      lower range of detection by the assays. The virus in all samples was quantitated
      by using a standard curve obtained by serial dilution of an in vitro transcript.
      By using the in vitro transcript, the lower limit of sensitivity was observed to
      be approximately 33 copies/ml. Reactivity with a panel of more than 100 PRRSV
      isolates from various geographical regions in the United States was also
      documented. No reactivity with nine nonrelated swine viruses was noted. A real
      time PCR was also developed for the detection of the European Lelystad virus and
      the European-like PRRSV now found in the United States. In six of six PRRSV
      inoculated boars, peak levels of viremia occurred at 5 days postinoculation (DPI)
      and were most consistently detectable throughout 22 DPI. In five of six boars,
      PRRSV was shed in semen for 0 to 2 days during the first 10 DPI; however, one of
      six boars shed the virus in semen through 32 DPI. Therefore, in general, the
      concentration and duration of PRRSV shedding in semen did not correlate with the
      quantity or duration of virus in serum. These differences warrant further studies
      into the factors that prevent viral replication in the reproductive tract.

PMID- 15472294
TI  - Instability of the restriction fragment length polymorphism pattern of open
      reading frame 5 of porcine reproductive and respiratory syndrome virus during
      sequential pig-to-pig passages.
AB  - Restriction fragment length polymorphism (RFLP) analysis is one of the tools
      commonly used to study the molecular epidemiology of porcine reproductive and
      respiratory syndrome viruses (PRRSVs). As PRRSVs are genetically variable, the
      stability of the RFLP pattern of a PRRSV during in vivo replication was evaluated
      by carrying out 13 sequential pig-to-pig passages (P1 to P13) of PRRSV ATCC VR
      2332 in three independent pig lines for a total of 727 days. During P1 the pigs
      were inoculated with a homogeneous inoculum (CC-01) prepared through a series of
      plaque purifications, and during P2 to P13 the pigs were inoculated with a tissue
      filtrate from the corresponding pig in the previous passage. Fifteen viral plaque
      clones were directly isolated from CC-01 and the day 7 serum of each pig of each
      passage, open reading frame 5 of the clones was sequenced, and the clones were
      compared to CC-01 to assess the mutation rates and RFLP patterns (obtained by
      digestion with MluI, HincII, and SacII) over time. Among the 495 viral clones
      recovered during the passages, 398 clones, including CC-01, had pattern 2-5-2
      (MluI-HincII-SacII); however, the remaining 97 viral clones showed different
      patterns (2-6-2 [P2], 1-5-2 [P3], 2-5-4 [P7], and 2-1-2 [P10]). Importantly, the
      MluI site that was reported to be present in only one of the PRRS modified live
      virus vaccine strains (Ingelvac) and its parental strain (ATCC VR-2332) can
      disappear during in vivo replication. Furthermore, sequence homology between CC
      01 and clones with pattern 2-5-2 or clones with other patterns differed by 0.05
      to 1.58% and 0.5 to 1.45%, respectively, suggesting that RFLP analysis cannot
      accurately predict genetic relatedness between PRRSVs. Collectively, precaution
      should be taken when the molecular epidemiology of PRRSVs is evaluated by RFLP
      analysis.

PMID- 15472295
TI  - Epidemiologic and molecular characterization of an outbreak of Candida
      parapsilosis bloodstream infections in a community hospital.
AB  - Candida parapsilosis is an important cause of bloodstream infections in the
      health care setting. We investigated a large C. parapsilosis outbreak occurring
      in a community hospital and conducted a case-control study to determine the risk
      factors for infection. We identified 22 cases of bloodstream infection with C.
      parapsilosis: 15 confirmed and 7 possible. The factors associated with an
      increased risk of infection included hospitalization in the intensive care unit
      (adjusted odds ratio, 16.4; 95% confidence interval, 1.8 to 148.1) and receipt of
      total parenteral nutrition (adjusted odds ratio, 9.2; 95% confidence interval,
      0.9 to 98.1). Samples for surveillance cultures were obtained from health care
      worker hands, central venous catheter insertion sites, and medical devices.
      Twenty-six percent of the health care workers surveyed demonstrated hand
      colonization with C. parapsilosis, and one hand isolate was highly related to all
      case-patient isolates by tests with the DNA probe Cp3-13. Outbreak strain
      isolates also demonstrated reduced susceptibilities to fluconazole and
      voriconazole. This largest known reported outbreak of C. parapsilosis bloodstream
      infections in adults resulted from an interplay of host, environment, and
      pathogen factors. Recommendations for control measures focused on improving hand
      hygiene compliance.

PMID- 15472296
TI  - Development of a multiplex PCR for the detection of asa1, gelE, cylA, esp, and
      hyl genes in enterococci and survey for virulence determinants among European
      hospital isolates of Enterococcus faecium.
AB  - A multiplex PCR for the simultaneous detection of five virulence genes (asa1,
      gelE, cylA, esp, and hyl) in enterococci was developed. The presence of these
      genes was investigated in 153 clinical and 118 fecal Enterococcus faecium
      isolates from inpatients at an increased risk of developing infections (such as
      patients in intensive care units and hematology wards) from 13 hospitals in eight
      European countries. Of the 271 E. faecium isolates, 135 were vancomycin resistant
      E. faecium (VREF) isolates and 136 were vancomycin susceptible E. faecium (VSEF)
      isolates. Susceptibilities to ampicillin, gentamicin, streptomycin, vancomycin,
      teicoplanin, ramoplanin, quinupristin-dalfopristin, and linezolid were tested by
      the microdilution method. Overall, the prevalence of esp was significantly higher
      (P = 0.03) in clinical VREF isolates (92%) than in fecal VREF isolates (73%). In
      Italy, the prevalence of esp was significantly higher (P = 0.02) in VREF isolates
      (91%) than in VSEF isolates (68%), whereas in the United Kingdom, hyl was
      significantly more prevalent (P = 0.01) in VREF isolates (71%) than in VSEF
      isolates (29%). No significant differences were found for the other countries.
      Pulsed-field gel electrophoresis was used to check the clonality among the
      strains tested and showed the spread of two center-specific (esp-positive) VREF
      clones in Italy and one center-specific (hyl-positive) clone in the United
      Kingdom. These clones were resistant to ampicillin, gentamicin, and streptomycin.
      The multiplex PCR reported in this study is a convenient and rapid method for the
      simultaneous detection of the virulence genes asa1, gelE, cylA, esp, and hyl in
      enterococci. Molecular analysis showed the intrahospital spread of esp-positive
      VREF clones (in Italy) and hyl-positive VREF clones (in the United Kingdom); the
      role of hyl remains to be elucidated.

PMID- 15472297
TI  - Detection of Paracoccidioides brasiliensis gp70 circulating antigen and follow-up
      of patients undergoing antimycotic therapy.
AB  - Paracoccidioidomycosis (PCM), one of the most important systemic mycoses in
      Central and South America, is caused by the dimorphic fungus Paracoccidioides
      brasiliensis and has a high prevalence in Brazil. Glycoproteins of 43 and 70 kDa
      are the main antigenic compounds of P. brasiliensis and are recognized by Western
      blotting by 100 and 96% of PCM patient sera, respectively. In the present study,
      an inhibition enzyme-linked immunosorbent assay (ELISA) was used to detect gp70
      in different biological samples from patients with PCM. gp70 was detected in
      98.76% of 81 serum samples, with an average concentration of 8.19 microg/ml. The
      test was positive for 100% of the patients with the acute and chronic unifocal
      forms of PCM and 98.43% of the patients with the multifocal chronic form, with
      average concentrations of 11.86, 4.83, and 7.87 microg/ml, respectively.
      Bronchoalveolar lavage fluid from 23 patients with pulmonary unifocal PCM and 14
      samples of cerebrospinal fluid from patients with neurological PCM were also
      tested for gp70 detection, with the test showing 100% sensitivity and 100%
      specificity, with mean gp70 concentrations of 7.5 and 6.78 microg/ml,
      respectively. To investigate the potential of gp70 detection by inhibition ELISA
      for the follow-up of PCM patients during antimycotic therapy with itraconazole
      (ITZ), the sera of 23 patients presenting with the chronic multifocal form of PCM
      were monitored at regular intervals of 1 month for 12 months. The results showed
      a decrease in circulating gp70 levels during treatment which paralleled the
      reduction in anti-P. brasiliensis antibody levels. The detection of P.
      brasiliensis gp70 from the biological fluids of patients suspected of having PCM
      proved to be a promising method for diagnosing infection and evaluating the
      efficacy of ITZ treatment.

PMID- 15472298
TI  - Tropheryma whipplei Infection of an acellular porcine heart valve bioprosthesis
      in a patient who did not have intestinal Whipple's disease.
AB  - Rare cases of culture-negative infective endocarditis are caused by Tropheryma
      whipplei, the uncommon bacterium of Whipple's disease. We evaluated an 80-year
      old woman with valvular heart disease but without intestinal Whipple's disease.
      The diagnosis of aortic valve xenograft culture-negative infection with T.
      whipplei was established by multiple molecular assays and by electron microscopy.
      First, a PCR with broad-range primers identified the complete 16S ribosomal DNA
      of T. whipplei in bioprosthesis tissue. Novel real-time reverse transcription-PCR
      assays were developed to detect mRNAs encoding recently identified proteins
      determined from the T. whipplei genome, specifically Whipplei surface protein
      (TW113) and a DNA polymerase III subunit (TW727). The positive detection of mRNAs
      indicated the presence of metabolically active bacteria and suggested the
      viability of T. whipplei. The quantification of T. whipplei genome equivalents by
      real-time PCR indicated a high-density bacterial colonization of the valve
      tissue. Additionally, an ultrastructural examination revealed numerous rod-shaped
      bacteria consistent in size with T. whipplei in the extracellular collagen matrix
      of the bioprosthesis. We conclude that extracellular growth of T. whipplei can
      occur in the microenvironment of biological prosthetic valve tissue and that T.
      whipplei endocarditis can occur in the absence of intestinal Whipple's disease.

PMID- 15472299
TI  - Genotyping of 44 isolates of Fusarium solani, the main agent of fungal keratitis
      in Brazil.
AB  - In a retrospective study performed over 6 years in Brazil, Fusarium solani was
      found to be the most common species causing mycotic keratitis. The genetic
      diversity of 44 isolates from 39 patients was assessed by enterobacterial
      repetitive intergenic consensus PCR (ERIC-PCR) and PCR restriction fragment
      length polymorphism (PCR-RFLP) fingerprinting. ERIC-PCR was more discriminatory
      than PCR-RFLP for differentiating the strains. By combining of the results of
      both techniques, we identified 40 genotypes. Molecular typing revealed a high
      genomic heterogeneity of the strains of F. solani studied.

PMID- 15472300
TI  - Detection of mutations associated with isoniazid and rifampin resistance in
      Mycobacterium tuberculosis isolates from Samara Region, Russian Federation.
AB  - High incidence rates of isoniazid-, rifampin-, and multiple-drug-resistant
      tuberculosis have been reported in countries of the former Soviet Union (FSU).
      Genotypic (unlike phenotypic) drug resistance assays do not require viable
      cultures but require accurate knowledge of both the target gene and the mutations
      associated with resistance. For these assays to be clinically useful, they must
      be able to detect the range of mutations seen in isolates from the population of
      tuberculosis patients to which they are applied. Two novel macroarrays were
      applied to detect mutations associated with rifampin (rpoB) and isoniazid (katG
      and inhA) resistance. In a sample of 233 isolates from patients in Samara,
      central Russia, 46.5% of isolates possessed mutations in both the rpoB and the
      katG (or inhA) genes. Combined results from the macroarrays demonstrated
      concordance in 95.4 and 90.4% of phenotypically defined rifampin- and isoniazid
      resistant isolates, respectively. The contribution of different mutations to
      resistance was comparable to that reported previously for non-FSU countries, with
      90% of rifampin-resistant isolates and 93% of isoniazid resistant isolates due to
      rpoB531 and katG315 mutations, respectively. The percentage of phenotypically
      resistant rifampin isolates with no mutations in the rpoB codons 509 to 536 was
      4.2%, which was similar to previous reports. Novel macroarrays offer a rapid,
      accurate, and relatively cheap system for the identification of rifampin-,
      isoniazid-, and multiple-drug-resistant Mycobacterium tuberculosis isolates.

PMID- 15472301
TI  - Multiple-locus variable-number tandem repeat analysis, a novel typing scheme to
      study the genetic relatedness and epidemiology of Enterococcus faecium isolates.
AB  - Multiresistant Enterococcus faecium is a major cause of hospital acquired
      infections and outbreaks. Here, we describe the development of multiple-locus
      variable-number tandem repeat (VNTR) analysis (MLVA) as a novel typing method to
      assess the genetic relatedness of E. faecium isolates. Six VNTR loci were used to
      genotype 392 isolates recovered from different animals and human community,
      hospital survey, and clinical isolates. From 3 to 13 alleles were found per
      locus, resulting in 127 different MLVA profiles. Clustering of MLVA profiles
      confirmed the host-specific genogroups found by multilocus sequence typing (MLST)
      and showed the grouping of clinical and epidemic isolates that belonged to the
      MLST-C1 cluster in a distinct MLVA-C1 cluster (sensitivity of 97% and specificity
      of 90%). Furthermore, the discriminatory power of MLVA is comparable to MLST.
      MLVA profiles appeared to be relatively stable, since isolates from a single
      outbreak shared the same MLVA profile, which is a prerequisite when MLVA is used
      to study hospital outbreaks. Our data show that MLVA is a highly reproducible and
      portable typing method; in contrast to MLST, it is fast, relatively cheap, and
      easy to perform. Furthermore, it has the abilities of MLST to recognize
      genetically related and potential epidemic isolates. Submission of MLVA profiles
      is possible via a Web-based database for international comparison.

PMID- 15472302
TI  - Novel real-time PCR assay for detection of Helicobacter pylori infection and
      simultaneous clarithromycin susceptibility testing of stool and biopsy specimens.
AB  - A biprobe real-time PCR protocol, followed by hybridization melting point
      analysis, to detect point mutations in the 23S rRNA gene of Helicobacter pylori
      associated with clarithromycin resistance was established and evaluated in a
      clinical study. Of 92 patients who underwent endoscopy, 45 were found to be H.
      pylori infected and invariably were also culture positive. Of the 45 isolates, 11
      were shown to be resistant to clarithromycin by E-test. With respect to the
      detection of H. pylori infection, PCR showed sensitivities of 100% in biopsies
      and 98% in stool specimens and a specificity of 98% in both biopsy and stool
      samples. All clarithromycin-sensitive cases were identified as such by PCR in
      both biopsy and stool samples. Of the cases with a resistant strain, eight were
      identified as such in stool DNA and nine were identified in biopsy DNA. Failure
      of PCR to detect the resistant genotype in the biopsy DNA, stool DNA, or both
      (one case) was associated with mixed populations. In these cases, patients had
      not been treated for H. pylori infection before, and the sensitive population
      showed to be present in considerably higher numbers than the resistant
      population. In five of six cases in which infection with a resistant genotype
      only was identified by PCR, the patients had received clarithromycin-based
      eradication therapy in the past. Thus, the assay presented provides a highly
      accurate noninvasive method to detect H. pylori infection in stool and at the
      same time allows for culture-independent clarithromycin susceptibility testing.

PMID- 15472303
TI  - Development and evaluation of a chromogenic agar medium for methicillin-resistant
      Staphylococcus aureus.
AB  - We describe here the development and evaluation of MRSA ID, a new chromogenic
      agar medium for the specific isolation and identification of methicillin
      resistant Staphylococcus aureus (MRSA). We used S. aureus ID (bioMerieux, La
      Balme Les Grottes, France) and supplemented it with various antimicrobials,
      including cefoxitin, ciprofloxacin, oxacillin, and methicillin. Cefoxitin proved
      to be superior to the other antimicrobials for the selection of MRSA from other
      strains of S. aureus. MRSA ID (consisting of S. aureus ID supplemented with 4 mg
      of cefoxitin/liter) was evaluated by the use of 747 swabs from various clinical
      sites. All specimens were also cultured on CHROMagar MRSA and oxacillin
      resistance screening agar base (ORSAB) and in selective mannitol broth (SMB). A
      total of 85 MRSA strains were isolated by a combination of all methods. After 22
      to 24 h of incubation, 80% of the MRSA strains were isolated as green colonies on
      MRSA ID, compared with 59 and 62% of the strains that were isolated as colored
      colonies on CHROMagar MRSA and ORSAB, respectively. After 48 h of incubation, 89,
      72, and 78% of the MRSA strains were isolated on MRSA ID, CHROMagar MRSA, and
      ORSAB, respectively. Sixty-five percent of the strains were isolated by growth in
      SMB. The specificities of MRSA ID, CHROMagar MRSA, ORSAB, and SMB were 99.5,
      99.3, 97.9, and 92.8%, respectively, after 22 to 24 h of incubation. We conclude
      that MRSA ID is a sensitive and specific medium for the isolation and
      identification of MRSA.

PMID- 15472304
TI  - Longitudinal study of viruses associated with canine infectious respiratory
      disease.
AB  - In this investigation a population of dogs at a rehoming center was monitored
      over a period of 2 years. Despite regular vaccination of incoming dogs against
      distemper, canine adenovirus type 2 (CAV-2), and canine parainfluenza virus
      (CPIV), respiratory disease was endemic. Tissue samples from the respiratory
      tract as well as paired serum samples were collected for analysis. The
      development of PCR assays for the detection of CPIV, canine adenovirus types 1
      and 2, and canine herpesvirus (CHV) is described. Surprisingly, canine adenovirus
      was not detected in samples from this population, whereas 19.4% of tracheal and
      10.4% of lung samples were positive for CPIV and 12.8% of tracheal and 9.6% of
      lung samples were positive for CHV. As reported previously, a novel canine
      respiratory coronavirus (CRCoV) was detected in this population (K. Erles, C.
      Toomey, H. W. Brooks, and J. Brownlie, Virology 310:216-223, 2003). Infections
      with CRCoV occurred mostly during the first week of a dog's stay at the kennel,
      whereas CPIV and CHV were detected at later time points. Furthermore, the
      evaluation of an enzyme-linked immunosorbent assay for detection of antibodies to
      CPIV and an immunofluorescence assay for detection of antibodies to CHV is
      described. This study shows that CPIV is present at kennels despite vaccination.
      In addition, other agents such as CHV and CRCoV may play a role in the
      pathogenesis of canine respiratory disease, whereas CAV-2 and canine distemper
      virus were not present in this population, indicating that their prevalence in
      the United Kingdom is low due to widespread vaccination of dogs.

PMID- 15472305
TI  - Nocardia mexicana sp. nov., a new pathogen isolated from human mycetomas.
AB  - Three isolates collected from human mycetomas and showing an unusual brownish
      purple pigmentation on Bennett agar plates were analyzed by a polyphasic
      taxonomic approach, including morphological, biochemical, physiological, and
      chemotaxonomic properties coupled with genomic and phylogenetic analysis. It
      clearly appeared that these microorganisms were distinct from their closest
      phenotypic and genetic match, the most related species according to 16S rRNA gene
      sequence analysis being Nocardia pseudobrasiliensis. The data obtained indicated
      that the three clinical strains should be recognized as a new species for which
      the name Nocardia mexicana sp. nov. is proposed.

PMID- 15472306
TI  - High rates of clustering of strains causing tuberculosis in Harare, Zimbabwe: a
      molecular epidemiological study.
AB  - We examined the pattern of tuberculosis (TB) transmission (i.e., reactivation
      versus recent transmission) and the impact of human immunodeficiency virus (HIV)
      infection in Harare, Zimbabwe. Consecutive adult smear-positive pulmonary TB
      patients presenting to an urban hospital in Harare were enrolled. A detailed
      epidemiological questionnaire was completed, and tests for HIV type 1 and CD4
      cell counts were performed for each patient. Molecular fingerprinting of the
      genomic DNA recovered from cultures of sputum was performed by two molecular
      typing methods: spacer oligonucleotide typing (spoligotyping) and analysis of
      variable number of tandem DNA repeats (VNTRs). A cluster was defined as isolates
      from two or more patients that shared the same spoligotype pattern or the same
      VNTR pattern, or both. DNA suitable for typing was recovered from 224 patients.
      The prevalence of HIV infection was 79%. Of 187 patient isolates (78.6%) typed by
      both spoligotyping and analysis of VNTRs, 147 were identified as part of a
      cluster by both methods. By spoligotyping alone, 84.1% of patient isolates were
      grouped into 20 clusters. The cluster size was generally <8 patient isolates,
      although three large clusters comprised 68, 25, and 23 patient isolates. A total
      of 89.4% of the patient isolates grouped into 12 clusters defined by analysis of
      VNTRs, with 2 large clusters consisting of 127 and 13 patient isolates,
      respectively. Thirty-six percent of patient isolates with a shared spoligotype
      and 17% with a shared VNTR pattern were geographically linked within Harare, but
      they were not linked on the basis of the patient's home district. In a
      multivariate analysis, there were no independent predictors of clustering,
      including HIV infection status. Comparison with the International Spoligotype
      database (Pasteur Institute, Pointe a Pitre, Guadeloupe) demonstrated that our
      three largest spoligotype clusters are well recognized and ubiquitous in Africa.
      In this epidemiologically well characterized urban population with a high
      prevalence of HIV infection, we identified a very high level of strain
      clustering, indicating substantial ongoing recent TB transmission. Geographic
      linkage could be detected in a proportion of these clusters. A small group of
      actively circulating strains accounted for most of the cases of TB transmission.

PMID- 15472307
TI  - Genotyping hepatitis C virus by heteroduplex mobility analysis using temperature
      gradient capillary electrophoresis.
AB  - The genotype of the infecting hepatitis C virus (HCV) helps determine the
      patient's prognosis and the duration of treatment. Heteroduplex mobility analysis
      (HMA) is a rapid, inexpensive method for genotyping of HCV that does not require
      sequencing. We developed an HMA that uses temperature gradient capillary
      electrophoresis (TGCE) to differentiate HCV genotypes. A 56-bp region of the HCV
      5' untranslated region (UTR) that was conserved within a genotype yet whose
      sequence differed between genotypes was amplified for HMA-TGCE analysis. HCV
      amplicons of types 1, 2a, 2b, 3a, 4, and 6a were hybridized in pairs and analyzed
      by TGCE. Amplicons hybridized to the same subtype yielded one homoduplex peak,
      while hybridization of different subtypes resulted in heteroduplexes and
      generated multiple TGCE peaks. Heteroduplexes contain thermodynamically unstable
      nucleotide mismatches that reduced their TGCE mobilities compared to those of
      homoduplexes. Three HCV subtypes (subtypes 1a, 3a, and 4) generated unique peak
      patterns when they were combined with each genotype analyzed and were chosen as
      the reference genotypes. A blinded study with 200 HCV-infected samples was 97%
      accurate compared to genotyping by 5' UTR sequence analysis. The majority of
      discordant results were unexpected sequence variants; however, five of nine
      sequence variants were correctly genotyped. The assay also detected and correctly
      genotyped mixed HCV infections. Compared to conventional HMA, TGCE improves the
      resolution, with better separation of heteroduplexes and homoduplexes. All common
      HCV genotypes can be detected and differentiated by this HMA-TGCE assay.

PMID- 15472308
TI  - Seroincidence of Coccidioidomycosis during military desert training exercises.
AB  - Coccidioidomycosis is a common fungal infection acquired in the southwestern
      United States. This is the first study in over 2 decades to determine the
      seroincidence of Coccidioides immitis infections among U.S. military members
      performing training exercises in an area of endemicity. Only 8% of participants
      were aware of coccidioidomycosis, despite the majority having visited or lived
      previously in an area of endemicity. One (0.6%) of the 178 participants developed
      "definite" serologic evidence of infection over a 5-week training period; four
      (2.3%) additional patients developed "possible" coccidioidomycosis infections.
      None had complicated disease. The calculated annual incidence ranged from 6 to
      32%. This study suggests that the risk of serious coccidioidomycosis is low among
      military personnel during desert training exercises; however, disease incidence
      may vary depending on specific activities and geographic factors. Due to the
      potential morbidity and mortality of this infection, preventative strategies,
      including vaccine development, are advocated.

PMID- 15472309
TI  - Molecular epidemiological analysis of Mycoplasma bovis isolates from the United
      Kingdom shows two genetically distinct clusters.
AB  - Mycoplasma bovis is an important veterinary pathogen causing pneumonia,
      arthritis, and mastitis in infected cattle. We investigated the genetic diversity
      of 53 isolates collected in the United Kingdom between 1996 and 2002 with pulsed
      field gel electrophoresis (PFGE), amplified fragment length polymorphism (AFLP),
      and random amplified polymorphic DNA (RAPD) analysis. In addition, the influence
      of variable surface protein (Vsp) profiles on the profiles generated with
      molecular typing techniques was studied. Both AFLP and RAPD separated the
      isolates into two distinct groups, but PFGE showed less congruence with the other
      techniques. There was no clear relationship between the geographic origin or year
      of isolation of the isolates and the profiles produced. No correlation between
      Vsp profiles and any of the molecular typing techniques was observed. We propose
      that RAPD and AFLP provide valuable tools for molecular typing of M. bovis.

PMID- 15472310
TI  - Large-scale comparative genomics meta-analysis of Campylobacter jejuni isolates
      reveals low level of genome plasticity.
AB  - We have used comparative genomic hybridization (CGH) on a full-genome
      Campylobacter jejuni microarray to examine genome-wide gene conservation patterns
      among 51 strains isolated from food and clinical sources. These data have been
      integrated with data from three previous C. jejuni CGH studies to perform a meta
      analysis that included 97 strains from the four separate data sets. Although many
      genes were found to be divergent across multiple strains (n = 350), many genes (n
      = 249) were uniquely variable in single strains. Thus, the strains in each data
      set comprise strains with a unique genetic diversity not found in the strains in
      the other data sets. Despite the large increase in the collective number of
      variable C. jejuni genes (n = 599) found in the meta-analysis data set, nearly
      half of these (n = 276) mapped to previously defined variable loci, and it
      therefore appears that large regions of the C. jejuni genome are genetically
      stable. A detailed analysis of the microarray data revealed that divergent genes
      could be differentiated on the basis of the amplitudes of their differential
      microarray signals. Of 599 variable genes, 122 could be classified as highly
      divergent on the basis of CGH data. Nearly all highly divergent genes (117 of
      122) had divergent neighbors and showed high levels of intraspecies variability.
      The approach outlined here has enabled us to distinguish global trends of gene
      conservation in C. jejuni and has enabled us to define this group of genes as a
      robust set of variable markers that can become the cornerstone of a new
      generation of genotyping methods that use genome-wide C. jejuni gene variability
      data.

PMID- 15472311
TI  - Clinical evaluation of the Sensititre YeastOne colorimetric antifungal plate for
      antifungal susceptibility testing of the new triazoles voriconazole,
      posaconazole, and ravuconazole.
AB  - A commercially prepared dried colorimetric microdilution panel (Sensititre
      YeastOne, TREK Diagnostic Systems, Cleveland, Ohio) was compared in three
      different laboratories with the National Committee for Clinical Laboratory
      Standards (NCCLS) reference microdilution method by testing two quality control
      strains and 300 clinical isolates of Candida spp. against fluconazole,
      voriconazole, posaconazole, and ravuconazole. Reference MIC endpoints were
      established after 48 h of incubation and YeastOne colorimetric endpoints were
      established after 24 h of incubation. YeastOne endpoints were determined to be
      the lowest concentration at which the color in the well changed from red
      (indicating growth) to purple (indicating growth inhibition) or blue (indicating
      no growth). Excellent agreement (within two dilutions) between the reference and
      colorimetric MICs was observed. Overall agreement was 95.4%. Agreement ranged
      from 92.3% with posaconazole to 98.0% with fluconazole. The YeastOne colorimetric
      method appears to be comparable to the NCCLS reference method for testing the
      susceptibility of Candida spp to the new triazoles voriconazole, posaconazole,
      and ravuconazole.

PMID- 15472312
TI  - Controlled clinical comparison of the BacT/ALERT FN and the standard anaerobic SN
      blood culture medium.
AB  - To determine the optimal anaerobic companion bottle to pair with the BacT/ALERT
      (bioMerieux, Durham, N.C.) nonvented aerobic FA (FA) medium for recovery of
      pathogenic microorganisms from adult patients with bacteremia and fungemia, we
      compared the BacT/ALERT FN (FN) anaerobic bottle with the standard BacT/ALERT SN
      (SN) anaerobic bottle. Each bottle, FA, FN, and SN, was filled with 8 to 12 ml of
      blood. Of 11,498 blood culture sets received in the clinical microbiology
      laboratories at two university medical centers, 7,945 sets had all three bottles
      filled adequately and 8,569 had both anaerobic bottles filled adequately. Of 686
      clinically important (based on previously published criteria) isolates detected
      in one or both adequately filled anaerobic bottles, more staphylococci (P <
      0.001), including Staphylococcus aureus (P < 0.001); members of the family
      Enterobacteriaceae (P < 0.001); and all microorganisms combined (P < 0.001) were
      detected in FN bottles. In contrast, more Pseudomonas aeruginosa isolates (P <
      0.01) and yeasts (P < 0.001) were detected in SN bottles. More Bacteroides
      fragilis group bacteremias were detected only in the FN (six) than in the SN
      (one) anaerobic bottle (P = not significant). Overall, the mean time to detection
      was shorter with FN (16.8 h) than with SN (18.2 h). This difference in time to
      detection was greatest for the B. fragilis group: FN, 28 h, versus SN, 60.0 h.
      Many of the facultative microorganisms recovered in either FN or SN were also
      found in the companion FA. When microorganisms found in the companion FA bottle
      were omitted from the analysis, significantly more staphylococci (P < 0.001),
      including S. aureus (P < 0.001), and Enterobacteriaceae (P < 0.005) still were
      detected in FN bottles, whereas there were no significant differences for P.
      aeruginosa and yeasts, which were found as expected in FA bottles. We conclude
      that the companion anaerobic FN bottle detects more microorganisms than does the
      anaerobic SN bottle when used in conjunction with the nonvented aerobic FA bottle
      in the BacT/ALERT blood culture system.

PMID- 15472313
TI  - Comparative analysis of Gtf isozyme production and diversity in isolates of
      Streptococcus mutans with different biofilm growth phenotypes.
AB  - Streptococcus mutans is the main pathogenic agent of dental caries.
      Glucosyltransferases (Gtfs) produced by these bacteria are important virulence
      factors because they catalyze the extracellular synthesis of glucans that are
      necessary for bacterial accumulation in the dental biofilm. The diversity of GtfB
      and GtfC isozymes was analyzed in 44 genotypes of S. mutans that showed a range
      of abilities to form biofilms in vitro. Several approaches were used to
      characterize these isozymes, including restriction fragment length polymorphism
      analysis of the gtfB and gtfC genes, zymographic analysis of the identified GtfB
      and GtfC genotypes, and quantitation of isozyme production in immunoblot
      experiments with specific monoclonal antibodies. A high diversity of gtf genes,
      patterns of enzymatic activity, and isozyme production was identified among the
      isolates tested. GtfC and, to a lesser extent, GtfB were produced in
      significantly higher amounts by strains that had high biofilm-forming ability
      than by strains with low biofilm-forming ability. Biofilm formation was
      independent of the GtfB and GtfC genotype. Atypical strains that showed an
      apparent single Gtf isozyme of intermediate size between GtfB and GtfC were also
      identified. The results indicate that various expression levels of GtfB and GtfC
      isozymes are associated with the ability of distinct S. mutans genotypes to grow
      as biofilms, strengthening the results of previous genetic and biochemical
      studies performed with laboratory strains. These studies also emphasize the need
      to identify factors that control gtf gene expression.

PMID- 15472314
TI  - Aqueous humor and serum immunoblotting for immunoglobulin types G, A, M, and E in
      cases of human ocular toxoplasmosis.
AB  - The purpose of this study was to compare the local and systemic Toxoplasma
      specific humoral immune responses in individuals with ocular toxoplasmosis (OT).
      To this end, paired aqueous humor and serum samples from 46 individuals with
      active OT and from 30 individuals without inflammatory eye disease (controls)
      were analyzed by immunoblotting for anti-Toxoplasma immunoglobulin G (IgG), IgA,
      IgM, and IgE directed against 20- to 120-kDa antigens. The presence in the
      aqueous humor of a unique band, or of at least three bands that were at least
      three times more intense in aqueous humor than in serum, was taken as evidence of
      local antibody production. IgG bands were detected in 98% of the aqueous humor
      samples, while IgA bands were detected in 76%, IgM bands were detected in 8%, and
      IgE bands were not detected in any. Evidence of local production of specific
      antibodies was found in 32 cases (70%) (IgG in 23 [50%]; IgA in 16 [35%]). In 10
      instances (22%), routine laboratory tests were not indicative of OT. In 14 cases
      (30%), no local antibody production was detected by immunoblotting; 3 of these
      cases yielded evidence of local antibody production according to the Goldmann
      Witmer coefficient. Local antibody production was revealed for 7 of the 30
      controls (23%). Hence, the sensitivity of immunoblotting for IgG and IgA is 70%,
      and the specificity is 77%. We conclude that immunoblotting for local specific
      IgG and IgA supports the clinical diagnosis of OT in 70% of cases. In 22% of
      these, the diagnosis is not confirmed by other laboratory tests. Hence,
      immunoblotting increases the sensitivity of routine laboratory tests and should
      be considered for samples that register negative by such tests.

PMID- 15472315
TI  - Performance assessment of a nested-PCR assay (the RAPID BAP-MTB) and the BD
      ProbeTec ET system for detection of Mycobacterium tuberculosis in clinical
      specimens.
AB  - The performance of a nested PCR-based assay (the RAPID BAP-MTB; AsiaGen,
      Taichung, Taiwan) and the BD ProbeTec ET (DTB) system (Becton Dickinson, Sparks,
      Md.) for detection of Mycobacterium tuberculosis was evaluated with 600
      consecutive clinical samples. These samples, including 552 respiratory specimens
      and 48 nonrespiratory specimens, were collected from 333 patients treated at
      National Taiwan University Hospital from September to October 2003. The results
      of both assays were compared to the gold standard of combined culture results and
      clinical diagnosis. The overall sensitivity and specificity of the RAPID BAP-MTB
      assay for respiratory specimens were 66.7% and 97.2%, respectively, and for the
      DTB assay they were 56.7% and 95.3%, respectively. The positive and negative
      predictive values for the RAPID BAP-MTB were 74.1% and 96.0%, respectively, and
      for the DTB assay they were 59.6% and 94.7%, respectively. For smear-negative
      samples, the sensitivity of the RAPID BAP-MTB and DTB assays was 57.1% and 40.5%,
      respectively. The RAPID BAP-MTB assay produced 14 false-positive results in 14
      samples, including one of the six samples yielding Mycobacterium abscessus, one
      of the six samples yielding Mycobacterium avium intracellulare, one sample from a
      patient with a history of pulmonary tuberculosis with complete treatment, and
      three samples from three patients with a previous diagnosis of tuberculosis who
      were under treatment at the time of specimen collection. Among the 48
      nonrespiratory specimens, the RAPID BAP-MTB assay was positive in one biopsy
      sample from a patient with lumbar tuberculous spondylitis and one pus sample from
      a patient with tuberculous cervical lymphadenopathy. Our results showed that the
      RAPID BAP-MTB assay is better than the DTB assay for both respiratory specimens
      and nonrespiratory specimens. The overall time for processing this assay is only
      5 h. In addition, its diagnostic accuracy in smear-negative samples is as high as
      in smear-positive samples.

PMID- 15472316
TI  - Relative importance of nasopharyngeal versus oropharyngeal sampling for isolation
      of Streptococcus pneumoniae and Haemophilus influenzae from healthy and sick
      individuals varies with age.
AB  - Streptococcus pneumoniae and Haemophilus influenzae carriage is a useful index
      for measuring the emergence of resistance and outcome in vaccination trials. We
      performed a study to determine which sampling site, nasopharynx (NP) or
      oropharynx (OP), yields the highest rate of S. pneumoniae and H. influenzae
      isolation at different ages. Both NP and OP cultures were obtained from 216
      children aged <60 months and their mothers. The total S. pneumoniae carriage rate
      was 68% among children and 15% among mothers (P < 0.001). Using NP alone for the
      isolation of S. pneumoniae would have missed 2, 2, and 42% and using OP alone
      would have missed 77, 66, and 45% of S. pneumoniae in children aged 0 to 23
      months, 24 to 59 months, and mothers, respectively. Using NP cultures alone for
      H. influenzae would have missed 23, 24, and 81% of the isolates, respectively.
      The respective figures for H. influenzae isolation from OP alone are 38, 29, and
      9%. In children, S. pneumoniae was carried mainly in the NP while H. influenzae
      was equally carried in the NP and OP. In mothers, S. pneumoniae was carried
      equally in the NP and OP while H. influenzae was carried significantly more often
      in the OP. In children, H. influenzae colonization increased during illness,
      mainly in the NP. Culturing only one site significantly reduced the recovery of
      H. influenzae at all ages. NP cultures for S. pneumoniae detected close to 100%
      of isolates in children but only 58% of isolates in mothers.

PMID- 15472317
TI  - Evidence of an antigenic shift among Palyam serogroup orbiviruses.
AB  - The Japanese isolates of Palyam serogroup viruses isolated from 1985 to 2001 were
      investigated for the genome sequence of segments 2 and 7 and were
      phylogenetically analyzed in comparison with Australian and African isolates of
      the same serogroup. The nucleotide sequences of segment 7 were highly conserved
      within Japanese isolates (95.1 to 100%) and between Japanese and Taiwanese
      isolates (96.0 to 100%), whereas the identities between Japanese and Taiwanese
      isolates and Australian and African isolates were fairly conserved (84.2 to
      92.0%). Phylogenetic analysis based on segment 7 revealed three clusters
      according to geographical origin. As a result of the nucleotide sequence analysis
      of segment 2, which encodes a serotype-specific antigen, Japanese isolates were
      classified into two groups by genome length and nucleotide identities. Four of
      the nine Japanese isolates were categorized into the same group as prototype
      strain K-47 of the Chuzan virus, and the remaining isolates were categorized into
      the same group as the D'Aguilar virus and Nyabira virus. Phylogenetic analysis
      based on segment 2 revealed two clusters, the cluster containing Chuzan virus and
      the cluster containing the D'Aguilar and Nyabira viruses. To examine the
      antigenic relationship among viruses categorized in different clusters, we
      conducted a cross-neutralization test. KSB-29/E/01, isolated in 2001 in Japan,
      was neutralized by antiserum not only to strain B8112 of D'Aguilar virus but also
      to Chuzan virus. These results indicated that genetically and antigenically
      unique characteristics of KSB-29/E/01 were attributed to genetic reassortment of
      segment 2 between Chuzan virus and D'Aguilar virus.

PMID- 15472318
TI  - Seroprevalence of antibodies against noroviruses among students in a Chinese
      military medical university.
AB  - Noroviruses (NVs) are important causes of nonbacterial gastroenteritis in humans,
      but the role of NVs as a cause of diseases in the Chinese people, particularly in
      Chinese military personnel, remains unclear. This study investigated antibody
      prevalence and factors that associate with the prevalence of antibody to NVs
      among students attending a military medical university. Serum specimens were
      tested by an enzyme-linked immunosorbent assay for immunoglobulin G antibody to
      recombinant capsid antigens of three NVs (rNorwalk, rMxV, and rVA387). Of 588
      serum samples tested, the antibody prevalence was 88.9, 54.1, or 90.0% for the
      three antigens, respectively. There were significant differences in the
      prevalence of antibody to rMxV between blood types (P < 0.05); the prevalence for
      type O was the highest (62.5%), and the prevalence for type B was the lowest
      (49.1%). The average optical density values for antibody to rNorwalk and rMxV
      were lowest among students with type B. The number of students who did not have
      antibody to any of the three antigens was the highest for blood type B (6.9%)
      compared to other blood types (0.8 to 3.4% [P < 0.006]). The antibody prevalence
      also varied with the hometown residencies of the students before joining the
      military, with the highest rates for students from rural areas, lower rates for
      students from small towns or villages, and the lowest rates for students from
      large cities. The numbers of students who did not have antibody to any of the
      three antigens were highest for students from the large cities, lower for
      students from small towns or villages, and lowest for students from rural areas.
      The distribution of ABO blood types did not differ among the three groups. These
      data suggest that NVs are prevalent in China and that both genetic and
      environmental factors play a role in NV infection.

PMID- 15472319
TI  - Longitudinal study of transmission, diversity, and stability of Streptococcus
      mutans and Streptococcus sobrinus genotypes in Brazilian nursery children.
AB  - The aim of this study was to perform a follow-up evaluation of the Streptococcus
      mutans and Streptococcus sobrinus colonization profile of children's oral
      cavities, which included the pattern of vertical transmission from mother to
      child, genotypic diversity, and stability of the strains. The subjects were 16
      mother-child pairs, who were monitored for 20 months. Samples of saliva, tongue
      dorsum, alveolar ridge mucosa, and dental plaque from the children were collected
      bimonthly. Saliva samples from the mothers were also collected. After isolation
      and identification, the arbitrarily primed PCR method was performed for the
      genotypic characterization of S. mutans (968 isolates) and S. sobrinus (111
      isolates). At the time the strains were acquired, the children harbored one to
      four distinct genotypes of S. mutans and only one genotype of S. sobrinus.
      Although S. mutans prevalence and genotypic diversity were greater than those of
      S. sobrinus, the presence of matching genotypes of S. mutans and S. sobrinus was
      similar (in 81.25 and 83.33% of mother-child pairs, respectively), suggesting
      vertical transmission for both species. This longitudinal study showed an
      increase in genotypic diversity of S. mutans in the oral cavity during the follow
      up period: most of the initially acquired genotypes persisted, normally those
      genotypes transmitted by the mother, and some were lost during follow-up; new
      strains were also acquired. In conclusion, S. mutans and S. sobrinus genotypes
      acquired from maternal or alternative sources may show effective persistence in
      the oral cavity and/or transitory detection in the children's mouths, reflecting
      the continuous development of oral microbiota in children.

PMID- 15472320
TI  - Evaluation of the immunoglobulin G avidity test for diagnosis of toxoplasmic
      lymphadenopathy.
AB  - Toxoplasmic lymphadenopathy (TL) is the most common clinical manifestation of
      acute acquired toxoplasma infection in normal individuals. The diagnosis is
      established by serologic methods and lymph node biopsy. Recently, tests for
      avidity of toxoplasma immunoglobulin G (IgG) antibodies have been introduced to
      help discriminate between recently acquired and distant infection with the
      parasite. We studied an avidity test to define the usefulness of this method and
      to determine the evolution of the IgG avidity in TL. Seventy-three consecutive
      patients diagnosed as having TL were studied. IgG avidity test titers were noted
      to be time dependent from the clinical onset of lymphadenopathy. Low IgG avidity
      test results were observed in patients who had developed lymphadenopathy from <1
      month to 17 months prior to the sampling of sera, emphasizing that low IgG
      avidity test results are not reliable for diagnosis of recently acquired
      infection. In contrast, high IgG avidity test results were observed only in
      patients who had developed lymphadenopathy at least 4 months earlier. Thus, a
      high IgG avidity test result in an individual who has recent onset of
      lymphadenopathy (e.g., within 2 to 3 months of sera sampling) suggests a cause
      other than toxoplasmosis. In such cases, further workup is warranted in order to
      determine the cause of the lymphadenopathy.

PMID- 15472321
TI  - Prospective study of human metapneumovirus infection in children less than 3
      years of age.
AB  - Most lower respiratory tract infections (LRTIs) in children under the age of 3
      years are due to respiratory syncytial virus (RSV). Epidemiological, host, and
      viral factors eventually account for the severity of LRTIs, but they do not
      completely explain it. Human metapneumovirus (hMPV) was recently identified in
      children with LRTIs. In a population-based prospective multicenter study (the
      PRI.DE study, conducted in Germany over 2 years), we tested 3,369 nasopharyngeal
      secretions from children younger than 3 years of age with LRTIs for RSV A and B,
      influenza viruses (IVs) A and B, and parainfluenza viruses (PIVs) 1 to 3. Of the
      children requiring intensive care (n = 85), 18% had hMPV infections, and 60% of
      these children were infected with hMPV in combination with RSV. We did not detect
      hMPV in a randomly selected subset of RSV-positive nasopharyngeal secretions (n =
      120) from children not requiring intensive care support. hMPV was detected in <1%
      of virus-negative samples from patients without intensive care support (n = 620).
      Our data support the hypothesis that coinfections with RSV and hMPV are more
      severe than infections with either RSV or hMPV alone, at least in children
      younger than 3 years of age.

PMID- 15472322
TI  - High prevalence of genital mycoplasmas among sexually active young adults with
      urethritis or cervicitis symptoms in La Crosse, Wisconsin.
AB  - Sexually active young adults in the small college town of La Crosse, Wisconsin,
      were evaluated for conventional sexually transmitted pathogens and tested for
      infections with mycoplasmas. The prevalence in 65 symptomatic men or women and
      137 healthy volunteers (67 men and 70 women) was compared. Urine specimens from
      both cohorts were tested by ligase chain reaction for Chlamydia trachomatis or
      Neisseria gonorrhoeae. In addition, the urethral or cervical swabs from the
      symptomatic subjects were tested by PCR for Mycoplasma genitalium and cultured
      for Mycoplasma hominis and the ureaplasmas. The results confirmed a relatively
      low prevalence of gonorrhea among symptomatic men (12%) and chlamydia among
      symptomatic men (15%) and normal women (3%). In contrast, infections with
      mycoplasmas, especially the ureaplasmas (57%), were common and the organisms were
      the only potential sexually transmitted pathogen detected in 40 (62%) symptomatic
      subjects. Because of the high prevalence, we also evaluated urethral swabs from
      an additional 25 normal female volunteers and recovered ureaplasmas from 4 (16%)
      subjects. Additionally, the participants rarely used protection during sexual
      intercourse and some symptomatic subjects apparently acquired their infections
      despite using condoms regularly. The findings demonstrate a strong association
      between abnormal urogenital findings and detection of myoplasmas, particularly
      ureaplasmas, and suggest the infections will remain common.

PMID- 15472323
TI  - Performance of immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays
      using a West Nile virus recombinant antigen (preM/E) for detection of West Nile
      virus- and other flavivirus-specific antibodies.
AB  - Focus Technologies developed an indirect immunoglobulin G (IgG) enzyme-linked
      immunosorbent assay (ELISA) and a mu-capture IgM ELISA for the detection of West
      Nile virus (WNV)-specific antibodies based on a WNV preM/E protein recombinant
      antigen. Normal and disease state serum panels were used to assess the
      performance characteristics of the two WNV ELISA kits. Totals of 807 and 1,423
      sera were used to assess the IgG ELISA and IgM ELISA kits, respectively. The
      Focus Technologies IgG ELISA had a sensitivity of 97.6% and a specificity of
      92.1% (excluding non-WNV flavivirus sera). The comparative method for WNV IgG may
      lack sensitivity in detecting IgG in early WNV infection, so the specificity of
      the Focus IgG ELISA may be higher than 92.1%. When sera from patients either
      infected with or vaccinated against other flaviviruses were tested on the WNV IgG
      assay, 35% of the sera reacted as positive for WNV IgG. Yellow fever and Japanese
      encephalitis vaccinees were less reactive in the IgG ELISA than St. Louis and
      dengue fever patients. The Focus Technologies IgM ELISA had a sensitivity and a
      specificity of 99.3% (excluding the non-WNV flavivirus sera). The overall cross
      reactivity for the IgM ELISA to flavivirus sera was 12%, with 31% of St. Louis
      encephalitis patients found to be WNV IgM positive and no yellow fever vaccinees
      found to be WNV IgM positive. In a selected population of 706 sera, 15 false
      positive WNV IgM sera were identified. The use of a background subtraction method
      for the IgM ELISA eliminated all 15 false-positive results, giving a specificity
      of 100% for the Focus IgM ELISA.

PMID- 15472324
TI  - Tracking methicillin-resistant Staphylococcus aureus clones during a 5-year
      period (1998 to 2002) in a Spanish hospital.
AB  - Three hundred seventy-five consecutive methicillin-resistant Staphylococcus
      aureus (MRSA) clinical isolates recovered between 1998 and 2002 at the Nuestra
      Senora de Candelaria University Hospital in Tenerife, Spain, were analyzed by
      molecular fingerprinting techniques to determine MRSA clonal types and their
      prevalence over time. After determining antibiotic susceptibility, we used SmaI
      digested genomic DNA separated by pulsed-field gel electrophoresis (PFGE) to
      characterize MRSA isolates and to establish PFGE types. Additionally, several
      selected isolates representative of each major PFGE type were tested by
      multilocus sequence typing (MLST) and by a multiplex PCR method capable of
      identifying the structural type of the staphylococcal cassette chromosome mec
      (SCCmec), generating the corresponding sequence type (ST)-SCCmec types. Results
      of PFGE, supported by those of MLST and SCCmec typing, allowed us to identify six
      MRSA clones within the five major PFGE types and document temporal shifts in the
      prevalence of these MRSA clones from 1998 to 2002. Four of the clones were the
      pandemic "Iberian" (designated ST247-MRSA-IA), EMRSA-15 (ST22-MRSA-IV), EMRSA-16
      (ST36-MRSA-II), and the so-called pediatric (ST5-MRSA-IV) clones, while the other
      two (ST125-MRSA-IVA and ST146-MRSA-IVA) clones could be derived from the
      pediatric one. The most striking temporal shift in the dominance of MRSA clones
      was the replacement of the multidrug-resistant and highly epidemic Iberian clone
      by the so-called British EMRSA-16 clone during the 5-year surveillance period.
      Our results are in accordance with previously stated findings showing the
      worldwide hospital dominance of relatively few pandemic and presumably virulent
      MRSA clones. We report for the first time the detection in Spain of the British
      EMRSA-15 and pediatric clones, as well as the abrupt replacement of the Iberian
      by the EMRSA-16 as the major MRSA clone.

PMID- 15472325
TI  - Evolutionary genetic analysis of the emergence of epidemic Vibrio cholerae
      isolates on the basis of comparative nucleotide sequence analysis and multilocus
      virulence gene profiles.
AB  - Vibrio cholerae, the causative agent of cholera, is a natural inhabitant of the
      aquatic ecosystem. We examined a unique collection of V. cholerae clinical and
      environmental isolates of widespread geographic distribution recovered over a 60
      year period to determine their evolutionary genetic relationships based on
      analysis of two housekeeping genes, malate dehydrogenase (mdh) and a chaperonin
      (groEL). In addition, the phylogenetic distribution of 12 regions associated with
      virulence was determined. Comparative sequence analysis of mdh revealed that all
      V. cholerae O1 and O139 serogroup isolates belonged to the same clonal lineage.
      Single-strand conformational polymorphism (SSCP) analysis of these O1 and O139
      strains at groEL confirmed the presence of an epidemic clonal complex. Of the 12
      virulence regions examined, only three regions, Vibrio seventh pandemic island 1
      (VSP-I), VSP-II, and RS1, were absent from all classical V. cholerae isolates.
      Most V. cholerae El Tor biotype and O139 serogroup isolates examined encoded all
      12 virulence regions assayed. Outside of V. cholerae O1/O139 serogroup isolates,
      only one strain, VO7, contained VSP-I. Two V. cholerae El Tor isolates, GP155 and
      2164-78, lacked both VSP-I and VSP-II, and one El Tor isolate, GP43, lacked VSP
      II. Five non-O1/non-O139 serogroup isolates had an mdh sequence identical to that
      of the epidemic O1 and O139 strains. These isolates, similar to classical
      strains, lack both VSP-I and VSP-II. Four of the 12 virulence regions examined
      were found to be present in all isolates: hlyA, pilE, MSHA and RTX. Among non
      O1/non-O139 isolates, however, the occurrence of the additional eight regions was
      considerably lower. The evolutionary relationships and multilocus virulence gene
      profiles of V. cholerae natural isolates indicate that consecutive pandemic
      strains arose from a common O1 serogroup progenitor through the successive
      acquisition of new virulence regions.

PMID- 15472326
TI  - Characterization of pathogenic Vibrio parahaemolyticus isolates from clinical
      sources in Spain and comparison with Asian and North American pandemic isolates.
AB  - In spite of the potential risk involved with contamination of seafood with Vibrio
      parahaemolyticus, there is a lack of information on the occurrence of pathogenic
      V. parahaemolyticus in Europe. This organism was isolated in 1999 from a large
      outbreak (64 cases admitted to a single hospital) associated with raw oyster
      consumption in Galicia, Spain, one of the most important regions in shellfish
      production worldwide. Two V. parahaemolyticus isolates from the 1999 Galicia
      outbreak, three additional clinical isolates obtained in the same period from
      hospitals in Spain, two reference strains from clinical sources, and five Spanish
      environmental isolates were examined. Seventeen isolates belonging to the
      pandemic clone isolated in Asia and North America were included in the study for
      comparison. All isolates were characterized by serotyping, PCR for virulence
      related genes, pulsed-field gel electrophoresis (PFGE), and plasmid analysis.
      Four of the five clinical isolates from hospitals in Spain belonged to serotype
      O4:K11; the remaining isolate was O4:K untypeable (KUT). All five isolates were
      positive for V. parahaemolyticus toxR and tlh (species-specific genes) and tdh
      and negative for trh and group-specific PCR (a PCR method for detection of the
      pandemic clone). PFGE analysis with NotI and SfiI discriminated the European
      isolates in two closely related PFGE types included in a homogeneous cluster,
      clearly differentiated from the Asian and North American isolates. The five
      environmental isolates belonged to serotypes O2:K28, O2:KUT, O3:K53, O4:KUT, and
      O8:K22 and were negative for all virulence genes. The five isolates were
      discriminated into five different PFGE types unrelated to any other isolate
      included in the study. While the virulence characteristics (tdh positive, trh
      negative) of the Spanish clinical isolates matched those of the O3:K6 clone from
      Asia and North America, they were clearly excluded from this clone by group
      specific PCR, PFGE, and serotyping. The results of this study suggest that a
      unique and specific clone could be related to the V. parahaemolyticus infections
      in Europe.

PMID- 15472327
TI  - Evaluation and validation of real-time reverse transcription-pcr assay using the
      LightCycler system for detection and quantitation of norovirus.
AB  - We developed an assay for the detection and quantitation of norovirus with the
      LightCycler SYBR Green-based real-time reverse transcription-PCR (real-time LC RT
      PCR) and previously published primers in the capsid and the polymerase gene. One
      hundred thirty-two stool specimens from the Provincial Laboratory for Public
      Health (Microbiology), Alberta, Canada, and the Centers for Disease Control and
      Prevention, Atlanta, Ga., were used to validate the new assay. The samples were
      collected from patients involved in outbreaks of acute gastroenteritis or
      children who presented with sporadic gastroenteritis. The real-time LC RT-PCR
      assay detected norovirus strains from three genogroup I (G-I) clusters (G-I/1, G
      I/2, and G-I/3) and 10 genogroup II (G-II) clusters (G-II/1, G-II/2, G-II/3, G
      II/4, G-II/6, G-II/7, G-II/10, G-II/12, G-II/15, and G-II/16). There was 100%
      concordance with the results from 58 stool specimens which tested positive by
      conventional RT-PCR assays. By dilution analysis, the real-time LC RT-PCR was
      10,000 times more sensitive than the conventional RT-PCR. The new assay increased
      the number of samples in which noroviruses were detected by 19%. The real-time LC
      RT-PCR had a wide dynamic range, detecting from 5 to 5 x 10(6) copies of RNA per
      reaction, resulting in a theoretical lower limit of detection of 25,000 copies of
      RNA per g of stool. No cross-reactions were found with specimens containing
      sapovirus, rotavirus, astrovirus, and adenovirus. Because of the high sensitivity
      and specificity of the assay with a relatively rapid and simple procedure, the
      real-time LC RT-PCR will be useful as a routine assay for the clinical diagnosis
      of norovirus infection.

PMID- 15472328
TI  - Accuracy of phenotypic and genotypic testing for identification of Streptococcus
      pneumoniae and description of Streptococcus pseudopneumoniae sp. nov.
AB  - We have identified an unusual group of viridans group streptococci that resemble
      Streptococcus pneumoniae. DNA-DNA homology studies suggested that a subset of
      these isolates represent a novel species that may be included in the S. oralis-S.
      mitis group of viridans group streptococci. We suggest that this novel species be
      termed Streptococcus pseudopneumoniae. A combination of phenotypic and genetic
      reactions allows its identification. S. pseudopneumoniae strains do not have
      pneumococcal capsules, are resistant to optochin (inhibition zones, less than 14
      mm) when they are incubated under an atmosphere of increased CO2 but are
      susceptible to optochin (inhibition zones, >14 mm) when they are incubated in
      ambient atmospheres, are not soluble in bile, and are positive by the GenProbe
      AccuProbe Pneumococcus test. The bile solubility test is more specific than the
      optochin test for identification of S. pneumoniae. Genetic tests for pneumolysin
      (ply) and manganese-dependent superoxide dismutase (sodA) and identification
      tests with a commercial probe, AccuProbe Pneumococcus, do not discriminate
      between the new species and S. pneumoniae.

PMID- 15472329
TI  - Phylogeny, clinical associations, and diagnostic utility of the pilin subunit
      gene (sfpA) of sorbitol-fermenting, enterohemorrhagic Escherichia coli O157:H-.
AB  - The plasmid-borne sfpA gene encodes the pilin subunit in sorbitol-fermenting (SF)
      enterohemorrhagic Escherichia coli (EHEC) O157:H-. We investigated the
      distribution of sfpA among 600 E. coli isolates comprising the complete E. coli
      standard reference (ECOR) and diarrheagenic E. coli (DEC) strain collections and
      clinical isolates associated with enteric disease. sfpA was detected in DEC3F SF
      EHEC O157:H- strain 493/89, each of 107 SF EHEC O157:H- clinical isolates, and 14
      Shiga toxin-negative SF E. coli O157:H- strains which contained eae, which
      encodes gamma-intimin, and fliC, which encodes the H7 antigen. sfpA was absent
      from all other strains, including the ECOR strain collection, all non-SF EHEC
      O157:H7 strains, and all E. coli O55:H7 strains (E. coli O55:H7 is the postulated
      ancestor of Shiga toxin-producing E. coli [STEC] O157). These results suggest
      that there was a single acquisition of the sfpA gene in the nonmotile SF E. coli
      O157 branch, presumably after the eae-encoding pathogenicity island (the locus of
      enterocyte effacement) was acquired and motility was lost. We then applied the
      sfpA PCR in combination with rfbO157, stx, and eae PCRs to screen 636 stool
      samples from patients with diarrhea or hemolytic-uremic syndrome for SF STEC
      O157:H-. In 27 cases, the simultaneous presence of the sfpA, eae, and rfbO157
      amplicons indicated the presence of SF E. coli O157:H- strains, and the result
      was subsequently confirmed by isolation. All but two of these strains possessed
      stx2. None of the other stool samples was positive by the sfpA PCR; 59 of these
      stool samples contained EHEC O157:H7. The sfpA gene can be recommended as a
      target for screening for SF E. coli O157:H-.

PMID- 15472330
TI  - Application of molecular fingerprinting for qualitative assessment of small
      intestinal bacterial diversity in dogs.
AB  - The aims of this study were to evaluate the use of molecular fingerprinting for
      assessment of bacterial diversity in canine duodenal juice and to evaluate the
      variation in the small intestinal microflora at repeated sampling. Two groups of
      dogs were used. Duodenal juice was collected from eight dogs euthanized for an
      unrelated project (group 1). Duodenal juice was also collected endoscopically
      from six dogs at weekly intervals for a total of 3 weeks (group 2). The variable
      V6-V8 region of bacterial 16S ribosomal DNA was amplified, and PCR amplicons
      separated by denaturing gradient gel electrophoresis (DGGE). The reproducibility
      of DGGE profiles and variations in bacterial diversity between dogs were
      evaluated by comparing similarity indices (Dice's coefficient; 100% represents
      complete identity) of DGGE profiles from group 1 dogs. Weekly variations in the
      flora of the small intestine were evaluated by comparison of DGGE profiles from
      different time points within the same individuals in group 2. The mean (+/-
      standard deviation) similarity of DGGE profiles of duodenal juice between the
      dogs in group 1 was 38.3 +/- 15.7% (range, 12.5 to 76.65%). There was a
      significantly higher variation in DGGE profiles between different dogs than
      between duplicates obtained from the same dog (P < 0.0001). DGGE profiles from
      samples collected at different time points varied within individuals, possibly
      due to variation over time or slight variation in sampling location. DGGE
      profiles indicate that dogs have a highly diverse microflora of the small
      intestine, with marked differences between individual dogs.

PMID- 15472331
TI  - Noninfectious recombinant antigen for detection of St. Louis encephalitis virus
      specific antibodies in serum by enzyme-linked immunosorbent assay.
AB  - Proper surveillance of virus activity and a timely response to viral outbreaks
      depend upon the rapid diagnosis of viral infections. The immunoglobulin M (IgM)
      antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) is a fast,
      sensitive test routinely used for the diagnosis of the medically important West
      Nile and St. Louis encephalitis flaviviruses. However, the suckling mouse brain
      derived (SMB) antigen used in this assay is tedious to prepare and has a risk of
      exposing personnel to live virus and hazardous chemicals. We report the
      development of a St. Louis encephalitis virus (SLEV) noninfectious recombinant
      antigen that is a safe and easily produced alternative antigen for use in
      diagnostic assays. The expression plasmid pCB8SJ2, containing the premembrane and
      envelope structural protein-encoding regions of SLEV, was constructed to express
      secreted extracellular virus-like particles (VLPs) from CHO cells. Blind-coded
      human serum panels were assembled from patients having recent SLEV, West Nile
      virus (WNV), Powassan virus, or La Crosse encephalitis virus infections to assess
      the sensitivity and specificity of assays with SLEV VLP or SMB antigen. MAC
      ELISAs with either antigen had comparable sensitivity for the detection of IgM
      antibodies against SLEV. Importantly, when these two antigens were tested against
      a human serum panel from patients having recent WNV or Powassan virus infections,
      the SLEV VLPs were less likely than SMB antigen to detect flavivirus cross
      reactive IgM antibodies. An optimized IgG antibody capture ELISA (GAC-ELISA) with
      both WNV and SLEV VLPs was developed to circumvent the frequently observed higher
      background in the antigen-capture IgG-ELISA (ACG-ELISA). For the detection of IgG
      antibodies against WNV, the GAC-ELISA resulted in a statistically significant
      higher performance accuracy (P = 0.003) than the ACG-ELISA when the WNV VLP
      antigen was used in both assays. However, no statistical difference was observed
      in the assay performance of the GAC-ELISA with SLEV VLP or the ACG-ELISA with
      SLEV SMB antigen.

PMID- 15472332
TI  - Type C botulism due to toxic feed affecting 52,000 farmed foxes and minks in
      Finland.
AB  - The largest reported outbreak of type C botulism in fur production animals is
      described. Epidemiological investigation of 117 out of 157 (response rate, 74.5%)
      farms revealed that 44,130 animals died or were euthanized, while 8,033 animals
      with milder symptoms recovered. The overall death rate in all animals at risk was
      21.7%. The death rates were significantly higher in blue and shadow foxes (24.2
      and 27.8%, respectively) than in silver and blue silver foxes and minks (below
      4%). All minks had been immunized against botulinum toxin type C. Deaths were
      associated with feed manufactured by a local processor, 83 of whose customer
      farms (70.9%) reported dead or sick animals. Five feedlots out of 19 delivered to
      the farms on the day preceding the onset of the outbreak (day 2) were associated
      with a death rate higher than 40%. These feedlots consisted of fresh feed
      processed on day 2 and feed processed 1 day earlier (day 1). In laboratory
      analysis, the day 2 feed contained botulinum toxin type C (>600 minimum lethal
      doses/g), while the day 1 feed did not contain toxin. Toxin was not detected in
      feed raw-material samples. Clostridium botulinum type C was detected by PCR in
      some feed components and in feed. However, as the feed temperature was
      continuously 8 degrees C or below and the pH was continuously 5.6 or below
      according to the manufacturer, it seems unlikely that spore germination and toxin
      formation occurred during overnight storage. Hence, the events leading to toxin
      formation were not determined.

PMID- 15472333
TI  - Differential expression of secretory aspartyl proteinase genes (SAP1-10) in oral
      Candida albicans isolates with distinct karyotypes.
AB  - Two karyotypes of oral Candida albicans isolates, named b and c, constituted >80%
      of a collection from healthy carriers (22 b and 16 c isolates) and oral
      candidiasis patients who were either infected (31 b and 16 c isolates) or
      uninfected (13 b and 38 c isolates) with human immunodeficiency virus (HIV). The
      prevalence of the b and c karyotypes within HIV-positive and HIV-negative
      patients, respectively, who were suffering from oral candidiasis (P < or =
      0.0001) suggested that these two types possessed different virulence potentials.
      Since C. albicans proteinases (Saps) are virulence factors in oral candidiasis,
      we evaluated whether the b and c karyotypes secreted different levels of Saps and
      expressed different patterns of Sap-encoding genes (SAP1-10). We found that the
      mean value of Sap activity was significantly lower (P = 0.003) in the commensal
      type than in the infectious b karyotype, whereas Sap activity in the commensal c
      type was as high as that registered for the infectious c strains. Marked
      differences in SAP mRNA expression were observed in commensal strains under non
      Sap-inducing conditions, with all SAP genes being expressed only by strains with
      the c karyotype; interestingly, none of the commensal b strains expressed SAP2.
      In addition, while all of the SAP1-10 genes were detectable under Sap-inducing
      conditions, the timing of their expression during growth differed significantly,
      with mRNAs of SAP1-10 genes detected at 8 and 24 h postinoculation in c and b
      commensal strains, respectively. This provides the first evidence that commensal
      oral C. albicans isolates with distinct karyotypes are characterized by different
      patterns of SAP1-10 gene expression and different levels of Sap secretion.

PMID- 15472334
TI  - Genetic diversity among community methicillin-resistant Staphylococcus aureus
      strains causing outpatient infections in Australia.
AB  - Increasing reports of the appearance of novel nonmultiresistant methicillin
      resistant Staphylococcus aureus MRSA (MRSA) strains in the community and of the
      spread of hospital MRSA strains into the community are cause for public health
      concern. We conducted two national surveys of unique isolates of S. aureus from
      clinical specimens collected from nonhospitalized patients commencing in 2000 and
      2002, respectively. A total of 11.7% of 2,498 isolates from 2000 and 15.4% of
      2,486 isolates from 2002 were MRSA. Approximately 54% of the MRSA isolates were
      nonmultiresistant (resistant to less than three of nine antibiotics) in both
      surveys. The majority of multiresistant MRSA isolates in both surveys belonged to
      two strains (strains AUS-2 and AUS-3), as determined by pulsed-field gel
      electrophoresis (PFGE) and resistogram typing. The 3 AUS-2 isolates and 10 of the
      11 AUS-3 isolates selected for multilocus sequence typing (MLST) and
      staphylococcal chromosomal cassette mec (SCCmec) analysis were ST239-MRSA-III
      (where ST is the sequence type) and thus belonged to the same clone as the
      eastern Australian MRSA strain of the 1980s, which spread internationally. Four
      predominant clones of novel nonmultiresistant MRSA were identified by PFGE, MLST,
      and SCCmec analysis: ST22-MRSA-IV (strain EMRSA-15), ST1-MRSA-IV (strain WA-1),
      ST30-MRSA-IV (strain SWP), and ST93-MRSA-IV (strain Queensland). The last three
      clones are associated with community acquisition. A total of 14 STs were
      identified in the surveys, including six unique clones of novel nonmultiresistant
      MRSA, namely, STs 73, 93, 129, 75, and 80slv and a new ST. SCCmec types IV and V
      were present in diverse genetic backgrounds. These findings provide support for
      the acquisition of SCCmec by multiple lineages of S. aureus. They also confirm
      that both hospital and community strains of MRSA are now common in
      nonhospitalized patients throughout Australia.

PMID- 15472335
TI  - Detection of galactomannan antigenemia in patients receiving piperacillin
      tazobactam and correlations between in vitro, in vivo, and clinical properties of
      the drug-antigen interaction.
AB  - Recent case reports describe patients receiving piperacillin-tazobactam who were
      found to have circulating galactomannan detected by the double sandwich enzyme
      linked immunosorbent assay (ELISA) system, leading to the false presumption of
      invasive aspergillosis. Since this property of piperacillin-tazobactam and
      galactomannan ELISA is not well understood, we investigated the in vitro, in
      vivo, and clinical properties of this interaction. Among the 12 reconstituted
      antibiotics representing four classes of antibacterial compounds that are
      commonly used in immunocompromised patients, piperacillin-tazobactam expressed a
      distinctively high level of galactomannan antigen in vitro (P = 0.001). After
      intravenous infusion of piperacillin-tazobactam into rabbits, the serum
      galactomannan index (GMI) in vivo changed significantly (P = 0.0007) from a
      preinfusion mean baseline value of 0.27 to a mean GMI of 0.83 by 30 min to slowly
      decline to a mean GMI of 0.44 24 h later. Repeated administration of piperacillin
      tazobactam over 7 days resulted in accumulation of circulating galactomannan to a
      mean peak GMI of 1.31 and a nadir of 0.53. Further studies revealed that the
      antigen reached a steady state by the third day of administration of piperacillin
      tazobactam. Twenty-six hospitalized patients with no evidence of invasive
      aspergillosis who were receiving antibiotics and ten healthy blood bank donors
      were studied for expression of circulating galactomannan. Patients (n = 13)
      receiving piperacillin-tazobactam had significantly greater mean serum GMI values
      (0.74 +/- 0.14) compared to patients (n = 13) receiving other antibiotics (0.14
      +/- 0.08) and compared to healthy blood bank donors (0.14 +/- 0.06) (P < 0.001).
      Five (38.5%) of thirteen patients receiving piperacillin-tazobactam had serum GMI
      values > 0.5 compared to none of thirteen subjects receiving other antibiotics (P
      = 0.039) and to none of ten healthy blood bank donors (P = 0.046). These data
      demonstrate that among antibiotics that are commonly used in immunocompromised
      patients, only piperacillin-tazobactam contains significant amounts of
      galactomannan antigen in vitro, that in animals receiving piperacillin-tazobactam
      circulating galactomannan antigen accumulates in vivo to significantly increased
      and sustained levels, and that some but not all patients receiving this
      antibiotic will demonstrate circulating galactomannan above the threshold
      considered positive for invasive aspergillosis by the recently licensed double
      sandwich ELISA.

PMID- 15472336
TI  - Use of multiple nucleic acid amplification tests to define the infected-patient
      "gold standard" in clinical trials of new diagnostic tests for Chlamydia
      trachomatis infections.
AB  - Nucleic acid amplification tests (NAATs) can be used to define the infected
      patient "gold standard" for the purpose of designing studies of the performance
      of Chlamydia trachomatis diagnostic tests. It is unclear how many test results
      run by different NAATs and what combinations of specimens comprise the best
      infected-patient gold standard. We approached this question with data from a
      large study of the performance of a new NAAT. Data were available from three
      endocervical swabs and a urine specimen collected from each of 1,412 women and
      tested by three different NAATs. Results from all three assays were used equally
      in a rotating fashion to define the infected-patient gold standard. Multiple
      different infected-patient gold standards for estimating swab and urine specimen
      sensitivity and specificity for one NAAT method were created by varying the
      number and combinations of swab and urine comparator results with two different
      NAATs, The effect of changing the infected-patient gold standard definition was
      determined by constructing receiver-operator-like curves with calculated
      sensitivities and specificities for each test. The one-positive-of-two-results or
      two-positive-of-two-results (same or two different assays) infected-patient gold
      standard definitions produced low sensitivity and low specificity estimates,
      respectively. If four comparator NAAT results were used, the any-three-positive
      of-four-results definition or the at-least-one-specimen-positive-by-each-of-two
      comparator-assays definition appeared to provide better combinations of
      sensitivity and specificity estimates. The any-two-positive-out-of-three-results
      definition resulted in estimates that were as good as produced with the former
      two definitions. This analytic approach provides a means of clearly visualizing
      the effects of changing NAAT-based infected-patient gold standards and should be
      helpful in designing future studies of new C. trachomatis diagnostic tests.

PMID- 15472337
TI  - Two novel real-time reverse transcriptase PCR assays for rapid detection of
      bacterial contamination in platelet concentrates.
AB  - The incidence of platelet bacterial contamination is approximately 1 per 2,000
      units and has been acknowledged as the most frequent infectious risk from
      transfusion. In preliminary studies, the sterility of platelet concentrates (PCs)
      was tested with an automated bacterial blood culturing system and molecular
      genetic assays. Two real-time reverse transcriptase PCR (RT-PCR) assays performed
      in a LightCycler instrument were developed and compared regarding specificity and
      sensitivity by the use of different templates to detect the majority of the
      clinically important bacterial species in platelets. Primers and probes specific
      for the conserved regions of the eubacterial 23S rRNA gene or the groEL gene
      (encoding the 60-kDa heat shock protein Hsp60) were designed. During the
      development of the 23S rRNA RT-PCR, problems caused by the contamination of
      reagents with bacterial DNA were noted. Treatment with 8-methoxypsoralen and UV
      irradiation reduced the level of contaminating DNA. The sensitivity of the assays
      was greatly influenced by the enzyme system which was used. With rTth DNA
      polymerase in a one-enzyme system, we detected 500 CFU of Escherichia coli or
      Staphylococcus epidermidis/ml. With a two-enzyme system consisting of Moloney
      murine leukemia virus RT and Taq DNA polymerase, we detected 16 CFU/ml. With
      groEL mRNA as the target of RT-PCR under optimized conditions, we detected 125
      CFU of E. coli/ml, and no problems with false-positive results caused by reagent
      contamination or a cross-reaction with human nucleic acids were found.
      Furthermore, the use of mRNA as an indicator of viability was demonstrated. Here
      we report the application of novel real-time RT-PCR assays for the detection of
      bacterial contamination of PCs that are appropriate for transfusion services.

PMID- 15472338
TI  - PCR assay using cerebrospinal fluid for diagnosis of cerebral toxoplasmosis in
      Brazilian AIDS patients.
AB  - Highly active antiretroviral therapy has decreased the incidence of opportunistic
      infections in the central nervous system in AIDS patients. However, neurological
      abnormalities still remain important causes of mortality and morbidity in
      developing countries. In Brazil, cerebral toxoplasmosis is the most common
      cerebral mass lesion in AIDS patients. For these reasons, early, inexpensive, and
      sensitive diagnostic tests must be evaluated. The aim of this study was to
      evaluate PCR, using cerebrospinal fluid (CSF) samples to detect Toxoplasma gondii
      DNA, and to determine if the association of PCR with immunological assays can
      contribute to a timely diagnosis. We studied two sample groups. First, we
      analyzed stored CSF samples from 29 newborns and from 39 adults with AIDS without
      a definitive diagnosis of toxoplasmosis. The goal of this step was to standardize
      the methodology with a simple and economical procedure to recover the T. gondii
      DNA. Next, we prospectively evaluated CSF samples from 12 AIDS patients with a
      first episode of cerebral toxoplasmosis and 18 AIDS patients with other
      neurological opportunistic diseases and without previous cerebral toxoplasmosis.
      In all PCR samples, an indirect immunofluorescent assay and an enzyme-linked
      immunosorbent assay were performed. Samples from all patients with cerebral
      toxoplasmosis presented positive PCR results (sensitivity, 100%), and a sample
      from one of the 18 AIDS patients with other neurological diseases also presented
      positive PCR results (specificity, 94.4%). These findings suggest the clinical
      utility of PCR in the diagnosis of cerebral toxoplasmosis in developing
      countries.

PMID- 15472339
TI  - Dramatic increase in prevalence of fecal carriage of extended-spectrum beta
      lactamase-producing Enterobacteriaceae during nonoutbreak situations in Spain.
AB  - The occurrence of extended-spectrum beta-lactamase (ESBL)-producing isolates has
      increased worldwide. Fecal carriage of ESBL-producing isolates has mainly been
      detected in nosocomial outbreaks, and few studies have evaluated fecal carriage
      during nonoutbreak situations and among patients in the community. We have
      studied the prevalence of ESBLs in 1,239 fecal samples from 849 patients (64.1%
      of whom were ambulatory) in 1991 and have compared the prevalence data with those
      obtained in 2003 for 400 fecal samples from 386 patients (75.9% of whom were
      ambulatory) and 108 samples from independent healthy volunteers. Samples were
      diluted in saline and cultured in two MacConkey agar plates supplemented with
      ceftazidime (1 microg/ml) and cefotaxime (1 microg/ml), respectively. Colonies
      were screened (by the double-disk synergy test) for ESBL production. The clonal
      relatedness of all ESBL-producing isolates was determined by pulsed-field gel
      electrophoresis with XbaI digestion; and the ESBLs of all ESBL-producing isolates
      were characterized by isoelectric focusing, PCR, and sequencing. The rates of
      fecal carriage of ESBL-producing isolates increased significantly (P < 0.001) in
      both hospitalized patients and outpatients, from 0.3 and 0.7%, respectively, in
      1991, to 11.8 and 5.5%, respectively, in 2003. The rate of occurrence of ESBL
      producing isolates among healthy volunteers was 3.7%. All ESBL-producing isolates
      recovered in 2003 were nonepidemic clones of Escherichia coli. ESBL
      characterization revealed an increasing diversity of ESBL types: TEM-4 and CTX-M
      10 were the only enzymes detected in 1991, whereas TEM-4, TEM-52, SHV-12, CTX-M
      9, CTX-M-10, CTX-M-14, and a CTX-M-2-like enzyme were recovered in 2003. The ESBL
      producing isolates recovered from outpatients in 2003 corresponded to a CTX-M-9
      type cluster (62.5%) and SHV-12 (31.2%), whereas TEM-4 was detected only in
      hospitalized patients. The frequencies of coresistance in isolates recovered in
      2003 were as follows: sulfonamide, 75%; tetracycline, 64.3%; streptomycin, 57.1%;
      quinolones, 53.5%; and trimethoprim, 50%. The increased prevalence of fecal
      carriage of ESBL-producing isolates during nonoutbreak situations in hospitalized
      patients and the establishment of these isolates in the community with
      coresistance to non-beta-lactam antibiotics, including quinolones, represent an
      opportunity for these isolates to become endemic.

PMID- 15472340
TI  - Comparison of trends of resistance rates over 3 years calculated from results for
      all isolates and for the first isolate of a given species from a patient.
AB  - We compared trends of annual resistance rates calculated from results for all
      isolates and for the first isolate of Staphylococcus aureus, Klebsiella
      pneumoniae, and Acinetobacter baumannii per patient over a 3-year period from
      2001 through 2003. Antimicrobial susceptibility results of inpatients were
      extracted from a computerized database. Annual resistance rates of a species were
      calculated by two methods: (i) from results for all isolates, even those from
      patients with multiple isolates in a given year and (ii) from results for the
      first isolate from a patient in a given year, regardless of susceptibility
      profile or specimen type. Rates of methicillin-resistant S. aureus (MRSA) did not
      differ among all isolates (79.9, 78.8 and 79.6%; P = 0.86), but decreased for the
      first isolate per patient (70.2, 65.7, and 64.1%; P = 0.006) over time. Annual
      duplication rates of methicillin-susceptible S. aureus (MSSA) decreased (39.6,
      37.6, and 31.7%; P = 0.01), but those of MRSA increased significantly (64.3,
      67.8, and 68.9%; P = 0.004). Rates of cefotaxime-resistant K. pneumoniae did not
      differ over time by either method, and rates of imipenem-resistant A. baumannii
      decreased over time by both methods. Duplication rates did not differ for either
      susceptible or resistant isolates of K. pneumoniae and A. baumannii. The trends
      in MRSA rate differed by the two methods because of the different proportion of
      duplicate isolates per year. MRSA rates might be increasingly overestimated for
      all isolates. These results suggest that the method of calculating results for
      the first isolate per patient may remove the effect of duplication, allowing the
      simple and unambiguous analysis of cumulative susceptibility rates.

PMID- 15472341
TI  - Adenovirus-mediated gene therapy enhances parainfluenza virus 3 infection in
      neonatal lambs.
AB  - Parainfluenza viruses are a common cause of seasonal respiratory disease, but in
      high-risk individuals (e.g., young children) these viruses can cause severe
      clinical manifestations that require hospitalization. Beta-defensins are a
      subclass of antimicrobial peptides with antiviral activity. Use of adenovirus
      mediated beta-defensin gene expression has been proposed as therapy for chronic
      bacterial infections commonly seen in cystic fibrosis patients; however, its use
      during parainfluenza virus 3 (PIV3) infection has not been evaluated. The
      hypothesis in this experiment was that adenovirus expression of human beta
      defensin 6 (HBD6) would diminish concurrent PIV3 infection in neonatal lambs. The
      group infected with adenovirus HBD6 and PIV3 had increased levels of pulmonary
      neutrophil recruitment compared to those for the group infected with PIV3 or PIV3
      and adenovirus, with an increased respiration rate and body temperature late in
      the course of the PIV3-adenovirus HBD6 infection. Interestingly, the adenovirus
      treated groups had higher levels of immunohistochemical staining for PIV3 and
      syncytial cell formation than the group infected with PIV3, suggesting that
      treatment with the adenovirus vector, regardless of whether it was carrying a
      target gene, exacerbated the PIV3 infection. The levels of expression of mRNA for
      antimicrobial surfactant proteins A and D and sheep beta-defensin 1 were
      increased by PIV3 and adenovirus treatment, and the increased levels of
      expression roughly corresponded to the degree of inflammation. While pulmonary
      administration of a high-dose adenovirus vector has been associated with
      undesirable inflammation, this is the first study to show that it can exacerbate
      concurrent viral infection, a concern that needs to be addressed for future
      studies of adenovirus in the lung. Additionally, this study showed that
      adenovirus-mediated HBD6 expression increases neutrophil recruitment, a recently
      described attribute of beta-defensins, with mild accentuation of PIV3 activity
      and inflammation.

PMID- 15472342
TI  - Pyrosequencing for detection of lamivudine-resistant hepatitis B virus.
AB  - Chronic hepatitis B virus (HBV) infection can cause severe liver disease,
      including cirrhosis and hepatocellular carcinoma. Lamivudine is a relatively
      recent alternative to alpha interferon for the treatment of HBV infection, but
      unfortunately, resistance to lamivudine commonly develops during monotherapy.
      Lamivudine-resistant HBV mutants display specific mutations in the YMDD
      (tyrosine, methionine, aspartate, aspartate) motif of the viral polymerase
      (reverse transcriptase [rt]), which is the catalytic site of the enzyme, i.e.,
      methionine 204 to isoleucine (rtM204I) or valine (rtM204V). The latter mutation
      is often accompanied by a compensatory leucine-to-methionine change at codon 180
      (rtL180M). In the present study, a novel sequencing method, pyrosequencing, was
      applied to the detection of lamivudine resistance mutations and was compared with
      direct Sanger sequencing. The new pyrosequencing method had advantages in terms
      of throughput. Experiments with mixtures of wild-type and resistant viruses
      indicated that pyrosequencing can detect minor sequence variants in heterogeneous
      virus populations. The new pyrosequencing method was evaluated with a small
      number of patient samples, and the results showed that the method could be a
      useful tool for the detection of lamivudine resistance in the clinical setting.

PMID- 15472343
TI  - Tobacco agar, a new medium for differentiating Candida dubliniensis from Candida
      albicans.
AB  - Isolates of Candida dubliniensis may be misidentified as Candida albicans in
      microbiological laboratories if only the germ tube and/or the chlamydospore test
      is used for identification to the species level. In this study, we have evaluated
      the efficacy of tobacco agar for the differentiation of C. dubliniensis from C.
      albicans. On this medium at 28 degrees C, all 30 C. dubliniensis isolates
      produced yellowish-brown colonies with hyphal fringes and abundant
      chlamydospores, whereas 54 C. albicans isolates formed smooth, white-to-cream
      colored colonies with no chlamydospore production. This medium provides a simple
      tool for presumptive differentiation of C. dubliniensis from C. albicans.

PMID- 15472344
TI  - New method for laboratory detection of AmpC beta-lactamases in Escherichia coli
      and Klebsiella pneumoniae.
AB  - A new cefoxitin-agar medium (CAM)-based assay was compared to the previously
      published modified three-dimensional (M3D) assay for the detection of AmpC
      production in Escherichia coli and Klebsiella pneumoniae. Clinical isolates of
      cefoxitin-resistant E. coli (n = 5) and K. pneumoniae (n = 7) and multiple
      control strains with and without AmpC enzymes were tested by both methods. The
      CAM method with 4 microg of cefoxitin/ml was equivalent to the M3D method for
      detecting AmpC production in E. coli and K. pneumoniae. This new method is easier
      to perform and interpret and allows for testing of multiple isolates on a single
      plate.

PMID- 15472345
TI  - Survival of Neisseria gonorrhoeae isolates of different auxotypes in six
      commercial transport systems.
AB  - We determined the rates of survival of six clinical and two control strains of
      Neisseria gonorrhoeae in six commercial transport systems, using NCCLS standard
      M40-A methodology. Differences in strain recovery and system performance were
      marked. A strain less robust than the recommended ATCC 43069 would provide a more
      exacting standard.

PMID- 15472346
TI  - Use of lung resection and voriconazole for successful treatment of invasive
      pulmonary Aspergillus ustus infection.
AB  - Invasive pulmonary aspergillosis (IPA) is a common infection in neutropenic
      patients and is associated with high mortality. Aspergillus ustus is a species
      that has only rarely been implicated in human disease. All reported cases of IPA
      due to A. ustus have been fatal. Here, we describe a case of invasive pulmonary
      A. ustus infection successfully treated with lung resection and voriconazole. A
      43-year-old man with acute myeloid leukemia underwent two courses of chemotherapy
      and experienced prolonged neutropenia. Treatment with amphotericin B was given
      for persistent fever. While he was receiving amphotericin B, a progressive
      opacity developed in the upper right lobe. Lung tissue obtained through pulmonary
      wedge resection for histology showed a mold with septate hyphae, consistent with
      IPA due to Aspergillus. A. ustus was grown in culture. The patient was then
      treated with voriconazole and remained in remission of the mold infection in
      spite of additional chemotherapy and a leukemic relapse. In summary, this report
      describes the successful treatment of invasive pulmonary A. ustus infection by
      lung resection and antifungal treatment with voriconazole in a neutropenic
      patient.

PMID- 15472347
TI  - Isolation of shiga toxin-producing Escherichia coli from a South American camelid
      (Lama guanicoe) with diarrhea.
AB  - Shiga toxin-producing Escherichia coli belonging to serotype O26:H11 was isolated
      from a 2-month-old guanaco with severe watery diarrhea. E. coli colonies carried
      the stx1 and eae genes, showed localized adherence to HEp-2 cells, and produced
      enterohemolysin. A serological response to lipopolysaccharide O26 was observed at
      the onset of diarrhea.

PMID- 15472348
TI  - Comparison of an immunochromatography test with multiplex reverse transcription
      PCR for rapid diagnosis of respiratory syncytial virus infections.
AB  - A new commercial rapid 10-min one-step immunochromatography (IC) test, SAS RSV
      test, was compared to another IC test, Directigen EZ RSV, employing RT-PCR as the
      "gold standard" for detecting respiratory syncytial virus. Of 102 clinical
      samples, 79 were positive by RT-PCR, 66 (82.5%) were positive with the SAS RSV
      test, and 55 (69.6%) were positive with Directigen EZ RSV. The specificity of the
      new test was 91.3% (21 of 23), similar to that of Directigen EZ RSV (100% [23 of
      23]). This test performs well enough to be used for patient care.

PMID- 15472349
TI  - In vitro antifungal susceptibility of Cryptococcus gattii.
AB  - We have determined the in vitro susceptibilities of 57 strains of Cryptococcus
      gattii to nine antifungal agents and have compared the MICs for these strains
      with those for C. neoformans. MICs were determined by a microdilution reference
      method. Albaconazole and ravuconazole (MICs of 0.04 and 0.05 microg/ml,
      respectively) showed the best activities. Micafungin showed no activity (MIC of
      >128 microg/ml). In general, C. gattii was less susceptible than C. neoformans to
      all drugs tested, with the exception of amphotericin B and flucytosine.

PMID- 15472350
TI  - Diagnostic value of reverse transcription-PCR of amniotic fluid for prenatal
      diagnosis of congenital rubella infection in pregnant women with confirmed
      primary rubella infection.
AB  - The diagnostic value of RT-PCR of amniotic fluid (AF) for prenatal diagnosis of
      congenital rubella virus infection in 45 pregnant women with confirmed primary
      infection was assessed. Specificity of RT-PCR was 100% and sensitivity ranged
      between 83 and 95%.

PMID- 15472351
TI  - Rapid and economical method for biochemical screening of stool isolates for
      Salmonella and Shigella species.
AB  - The LOUIS test is a screening protocol for Salmonella and Shigella that uses
      rapid enzyme tests. It had a sensitivity of 100% and a specificity of 94% and
      achieved presumptive reporting of Salmonella 3 h after colony isolation with
      savings of time and money compared to commercial identification systems.

PMID- 15472352
TI  - Species distribution and ribotype diversity of Burkholderia cepacia complex
      isolates from French patients with cystic fibrosis.
AB  - A total of 153 Burkholderia cepacia strains obtained from 153 French patients
      with cystic fibrosis were identified as Burkholderia multivorans (51.6%) or
      Burkholderia cenocepacia (45.1%). Eighty-two genotypes were identified using
      PvuII and EcoRI ribotyping. B. multivorans genotype A (found in 32 French
      patients) and two other genotypes were also identified among isolates from
      Austrian, German, Italian, and Canadian patients.

PMID- 15472353
TI  - First case of Arthrographis kalrae ethmoid sinusitis and ophthalmitis in the
      People's Republic of China.
AB  - We present here the first case in the People's Republic of China of human disease
      caused by the fungus Arthrographis kalrae. The male patient had fungal
      panophthalmitis and invasive sinusitis involving the maxillary and ethmoid
      sinuses. He was an apparently healthy man before receiving trauma to his left
      eye. He complained of pain and loss of visual acuity in the injured eye, which
      displayed redness and edema and eventually discharged pus. His symptoms became
      more severe after he was treated with steroids and several antibacterial agents.
      A computed tomography scan of the left eye revealed that the maxillary and
      ethmoid sinuses were involved. A smear of purulent material from the left eye
      orbit revealed fungal elements, and cultures of the material grew a fungus. The
      isolate was identified as A. kalrae based on gross and microscopic morphologies,
      biochemical assays, and DNA sequence analysis. The patient received amphotericin
      B intravenously, itraconazole orally, and atomized allitridum by nebulizing
      allitridum therapy. The patient's wound healed following surgical intervention,
      but the patient lost the use of his left eye. This case should remind
      ophthalmologists and other clinicians to consider the possibility of infections
      being fungal when antibacterial agents have no effect and the patient's condition
      worsens.

PMID- 15472354
TI  - Universal high-level primary metronidazole resistance in Helicobacter pylori
      isolated from children in Egypt.
AB  - Antimicrobial susceptibility testing was performed on 48 isolates of Helicobacter
      pylori recovered from Egyptian children undergoing routine endoscopies. The
      isolates were universally highly resistant to metronidazole, but resistance to
      other tested antimicrobial agents was rare (4% for clarithromycin, erythromycin,
      and azithromycin resistance versus 2% for ciprofloxacin and ampicillin
      resistance). Use of metronidazole for the treatment of H. pylori in Egypt should
      be avoided.

PMID- 15472355
TI  - Detection of catheter-related bloodstream infections by the differential-time-to
      positivity method and gram stain-acridine orange leukocyte cytospin test in
      neutropenic patients after hematopoietic stem cell transplantation.
AB  - For febrile neutropenic patients who received hematopoietic stem cell
      transplantation, the Gram stain-acridine orange leukocyte cytospin (AOLC) test
      and the differential-time-to-positivity method (DTP) were performed. As a
      diagnostic tool for catheter-related bloodstream infections in these patients,
      the Gram stain-AOLC test has a lower sensitivity than does the DTP method but
      acceptable positive and negative predictive values.

PMID- 15472356
TI  - Clinical benefit of recovering dermatophytes from skin swabs sent for bacterial
      culture.
AB  - We incubated Sabouraud dextrose agar plates to recover dermatophytes from skin
      swabs sent for bacterial culture. Dermatophytes were recovered from 66 (0.3%) of
      22,613 cultures. Twenty-one patients received specific antifungal treatment when
      their dermatophyte was reported. Most clinicians thought recovering and reporting
      the dermatophyte contributed to patient management.

PMID- 15472357
TI  - Sequence-based typing of flaB is a more stable screening tool than typing of flaA
      for monitoring of Campylobacter populations.
AB  - Different typing schemes for Campylobacter spp. were evaluated with 70 outbreak
      and sporadic isolates. The discriminatory indexes were 0.944 (by pulsed-field gel
      electrophoresis), 0.920 (by genotyping of the flagellin A gene), 0.902 (by
      genotyping of flaB), and 0.886 (by multilocus sequence typing). Cross
      classification gave 94.77 or 95.82% (PFGE-flaA or PFGE-flaB) concordance. flaA
      was overdiscriminatory in three cases, most probably due to intragenomic
      recombination.

PMID- 15472358
TI  - Fluorescent amplified fragment length polymorphism subtyping of multiresistant
      Salmonella enterica serovar Typhimurium DT104.
AB  - Fluorescent amplified fragment length polymorphism (FAFLP) subtyping analysis was
      used to genotype multiresistant Salmonella enterica serovar Typhimurium
      definitive phage type 104. Thirteen distinct FAFLP profiles were found among 85
      isolates exhibiting identical pulsed-field gel electrophoresis (PFGE) profiles. A
      single FAFLP profile was shared by 93% of outbreak-associated isolates and 82% of
      sporadic isolates. This study demonstrates the value of FAFLP as a high
      resolution tool for epidemiological investigation of Salmonella.

PMID- 15472360
TI  - Multiplex detection of mutations in clinical isolates of rifampin-resistant
      Mycobacterium tuberculosis by short oligonucleotide ligation assay on DNA chips.
AB  - A new approach, short-oligonucleotide-ligation assay on DNA chip (SOLAC), is
      developed to detect mutations in rifampin-resistant Mycobacterium tuberculosis.
      The method needs only four common probes to detect 15 mutational variants of the
      rpoB gene within 12 h. Fifty-five rifampin-resistant M. tuberculosis isolates
      were analyzed, resulting in 87.3% accuracy and 83.6% concordance relative to DNA
      sequencing.

PMID- 15472359
TI  - icaA is not a useful diagnostic marker for prosthetic joint infection.
AB  - A collection of 99 staphylococcal isolates associated with prosthetic joint
      infection and 23 coagulase-negative staphylococci isolated from noninfected
      arthroplasty-associated specimens were screened in order to determine whether the
      presence of icaA could be used to distinguish between pathogens and nonpathogens.
      All Staphylococcus aureus prosthetic joint infection isolates (n = 55) were icaA
      positive. A total of 46% (20 out of 44) of coagulase-negative staphylococcal
      prosthetic joint infection isolates were icaA positive, and 30% (7 out of 23) of
      arthroplasty-associated non-prosthetic joint infection-associated coagulase
      negative staphylococcal isolates were icaA positive (P = 0.23). Certain coagulase
      negative Staphylococcus species appeared more likely to be isolated as either
      arthroplasty-associated non-prosthetic joint infection-associated isolates (e.g.,
      Staphylococcus warneri and Staphylococcus hominis) or pathogens (e.g.,
      Staphylococcus lugdunensis). The presence of icaA in a coagulase-negative
      staphylococcal isolate associated with an arthroplasty is not a useful diagnostic
      indicator of pathogenicity.

PMID- 15472361
TI  - Performance of the Binax NOW Streptococcus pneumoniae urinary antigen assay for
      diagnosis of pneumonia in children with underlying pulmonary diseases in the
      absence of acute pneumococcal infection.
AB  - The performance of the Binax NOW immunochromatographic test for detecting
      Streptococcus pneumoniae antigen in urine specimens from 103 children presenting
      underlying pulmonary diseases with no recent pneumococcal infection was assessed.
      Our data indicate that this assay is unlikely to be useful for discriminating
      between children with and without pneumococcal pneumonia.

PMID- 15472362
TI  - Antimicrobial susceptibility of Helicobacter pylori strains isolated in
      Bangladesh.
AB  - Antimicrobial susceptibility of 120 Helicobacter pylori isolates to
      metronidazole, tetracycline, clarithromycin, and amoxicillin was determined, and
      77.5, 15, 10, and 6.6% of the isolates, respectively, were resistant. Only rdxA
      inactivation and both rdxA and frxA inactivation were responsible for
      metronidazole resistance in 66% (8 of 12) and 33% (4 of 12) of the isolates,
      respectively.

PMID- 15472363
TI  - Comparative analysis of the Schleicher and Schuell IsoCode Stix DNA isolation
      device and the Qiagen QIAamp DNA Mini Kit.
AB  - Efficient, rapid, and reproducible procedures for isolating high-quality DNA
      before PCR gene amplification are essential for the diagnostic and molecular
      identification of pathogenic bacteria. This study evaluated the Qiagen QIAamp DNA
      Mini Kit and the Schleicher and Schuell IsoCode Stix DNA isolation device for
      isolating nucleic acid. Buffer, serum, and whole-blood samples were spiked with
      Bacillus anthracis Sterne vegetative cells and Yersinia pestis, while water was
      spiked with B. anthracis Sterne spores. Although minimal variations in limit of
      detection occurred among matrices, both the IsoCode Stix extraction method and
      the Qiagen procedure have comparable detection limits.

PMID- 15472364
TI  - Performance of the TechLab C. DIFF CHEK-60 enzyme immunoassay (EIA) in
      combination with the C. difficile Tox A/B II EIA kit, the Triage C. difficile
      panel immunoassay, and a cytotoxin assay for diagnosis of Clostridium difficile
      associated diarrhea.
AB  - We compared a recently marketed enzyme immunoassay for glutamate dehydrogenase
      (GDH), TechLab's C. DIFF CHEK-60 (TL-GDH), in combination with the C. difficile
      Tox A/B II enzyme immunoassay (Tox-A/B) with (i) the Triage C. difficile test,
      which detects both GDH (TR-GDH) and toxin A (TR-Tox-A); (ii) an in-house
      cytotoxin assay (C-Tox); and (iii) stool cultures for C. difficile. All C.
      difficile isolates were tested for the presence of the toxin genes by PCR. If a
      toxin gene-positive strain of Clostridium difficile was recovered and a toxin was
      detected by any method, the result was considered to be truly positive. Eighty
      seven of 93 and 79 of 93 C. difficile culture-positive samples were also TL-GDH
      and TR-GDH positive, respectively. No test was able to detect toxin in all
      samples with true-positive results. Tox-A/B and TR-Tox-A in combination with the
      GDH detection tests and C-Tox were able to identify 52 and 50 samples with true
      positive results. Tox-A/B and TR-Tox-A would have missed 15 and 31% of cases of
      C. difficile-associated diarrhea, respectively, if used alone.

PMID- 15472365
TI  - Pooling of clinical specimens prior to testing for Chlamydia trachomatis by PCR
      is accurate and cost saving.
AB  - The accuracy and cost savings of pooling specimens prior to testing for Chlamydia
      trachomatis by PCR were evaluated with genital and urine specimens (n = 2,600).
      There was a 60% reduction in tests without significant loss of accuracy. The
      efficiency of pooling vaginal swabs is demonstrated for the first time.

PMID- 15472366
TI  - Association between phospholipase production by Malassezia pachydermatis and skin
      lesions.
AB  - An evaluation was made of the phospholipase activities of Malassezia
      pachydermatis strains isolated from healthy dogs versus those from dogs with
      dermatitis and otitis. A high percentage of strains of M. pachydermatis obtained
      from lesion sites (93.9%) produced phospholipase, compared to the strains
      obtained from healthy skin of the same dog with localized lesions (41.4%) and
      healthy dogs (10.6%).

PMID- 15472367
TI  - Routine use of a commercial test, GLABRATA RTT, for rapid identification of
      Candida glabrata in six laboratories.
AB  - When evaluated in six clinical laboratories from six countries with 1,174 fresh
      isolates, including 715 Candida glabrata and 459 non-C. glabrata strains,
      GLABRATA RTT (Fumouze Diagnostics, Levallois Perret, France) yielded an overall
      sensitivity and an overall specificity of 95.8 and 98.9%, respectively. The
      results were consistent from one laboratory to another. The five false-positive
      results corresponded to C. parapsilosis (n = 2), C. tropicalis, C.
      guilliermondii, and C. lusitaniae. GLABRATA RTT allows a rapid, cost-effective,
      and reliable presumptive identification of C. glabrata.

PMID- 15472368
TI  - Antigen assay with the potential to aid in diagnosis of blastomycosis.
AB  - We report results of an immunoassay for Blastomyces dermatitidis antigenuria.
      Sensitivity was 92.9%, and specificity was 79.3%. Cross-reactions occurred in
      96.3% of patients with histoplasmosis, 100% of patients with
      paracoccidioidomycosis, 70% of patients with penicilliosis marneffei, 2.9% of
      patients with cryptococcosis, and 1.1% of patients with aspergillosis.
      Reproducibility was 96.3%. These findings support a potential role for antigen
      testing in blastomycosis.

PMID- 15472369
TI  - Single-nucleotide polymorphisms in the rRNA operon and variable numbers of tandem
      repeats in the lipoprotein gene among Mycoplasma genitalium strains from clinical
      specimens.
AB  - We characterized the single-nucleotide polymorphisms in the rRNA operon and
      variable numbers of tandem repeats in the lipoprotein gene MG309 among Mycoplasma
      genitalium strains from clinical specimens by PCR and sequencing. Analysis of 31
      M. genitalium-infected patient specimens and 7 American Type Culture Collection
      strains identified six types of rRNA sequences and 11 different numbers of MG309
      repeats. Examination of sequential specimens from 10 patients showed that these
      genotypes were stable for at least 5 weeks. These data suggest the potential
      usefulness of the rRNA genotypes and the MG309 repeats for genotyping of M.
      genitalium.

PMID- 15472370
TI  - Multilocus variable-number tandem-repeat polymorphism among Brazilian
      Enterococcus faecalis strains.
AB  - Multilocus variable-number tandem-repeat analysis (MLVA) for seven genomic loci
      was developed for Enterococcus faecalis. MLVA and pulsed-field gel
      electrophoresis (PFGE) resulted in 37 and 31 genotypes among 83 strains,
      respectively. Both typing schemes were highly concordant (90.4%). MLVA is an
      excellent alternative to PFGE.

PMID- 15472371
TI  - HBsAg seroclearance in Chinese patients receiving lamivudine therapy for chronic
      hepatitis B virus infection.
AB  - We report two Chinese patients in whom lamivudine treatment resulted in HBsAg
      seroclearance. One patient received lamivudine, and another patient received 12
      week famciclovir treatment followed by lamivudine. Lamivudine was maintained
      after HBeAg seroconversion. These two patients lost HBsAg at 24 and 27 months
      (ages, 23 and 19.3 years, respectively) and developed measurable titer of anti
      HBs after 65 and 71 months of therapy, respectively. The liver biochemistry was
      normal after HBeAg seroconversion. The serum hepatitis B virus (HBV) DNA levels
      were undetectable (<200 copies/ml) both at the time of HBeAg seroconversion and
      at the last follow-up. Liver biopsy of one patient showed nearly normal
      histology, with undetectable intrahepatic total HBV DNA and covalently closed
      circular DNA. In conclusion, lamivudine therapy can result in HBsAg seroclearance
      at an early age even though the phenomenon is rare.

PMID- 15472372
TI  - Pediatric infection due to multiresistant Salmonella enterica serotype Infantis
      in Honduras.
AB  - We report the case of a pediatric patient with a Salmonella enterica serotype
      Infantis infection. Detailed microbiological investigation revealed that this
      isolate carries four beta-lactamase genes (bla(TEM-1b) variant, bla(SHV-5),
      bla(CTX-M-15), and bla(CMY-2)) conferring resistance to all beta-lactams but
      imipenem. This is the first report of a Salmonella isolate with CTX-M and AmpC
      enzymes on the American continent, the first report of bla(CMY-2) in Salmonella
      serotype Infantis, and the first report of bla(CTX-M-15) in the genus Salmonella.

PMID- 15472373
TI  - Culture-negative neonatal meningitis and endocarditis caused by Streptococcus
      agalactiae.
AB  - We describe a case of culture-negative meningitis and endocarditis caused by
      Streptococcus agalactiae in a 27-day-old boy. S. agalactiae was detected in
      cerebrospinal fluid and serum by broad-spectrum PCR amplification.

PMID- 15472374
TI  - Rothia dentocariosa septicemia without endocarditis in a neonatal infant with
      meconium aspiration syndrome.
AB  - Rothia dentocariosa, a gram-positive coccoid- to rod-shaped bacterium with
      irregular morphology, is a rare cause of bacteremia in patients without
      endocarditis. We report the first case of R. dentocariosa septicemia without
      endocarditis, which occurred in a neonatal infant with meconium aspiration
      syndrome.

PMID- 15472375
TI  - Mitral bioprosthetic valve endocarditis caused by an unusual microorganism,
      Gemella morbillorum, in an intravenous drug user.
AB  - We report a case of Gemella morbillorum mitral bioprosthetic valve endocarditis
      with perivalvular extension in a 44-year-old human immunodeficiency virus
      positive man who is an active intravenous drug user together with review of all
      published cases. This is only the second reported case of Gemella morbillorum
      endocarditis in a patient with a prosthetic valve.

PMID- 15472377
TI  - Eumycetoma caused by Cladophialophora bantiana in a dog.
AB  - We report a case of eumycetoma due to Cladophialophora bantiana in a 3-year-old
      male Siberian Husky living in France. The dog presented a tumefaction on the
      thorax and deformity of the second and third subjacent ribs, which were
      surgically removed. Macroscopic black granules were visible on the ribs, and
      direct microscopic examination revealed their fungal origin. Cultures yielded
      pure colonies of C. bantiana. The identification of the causative agent was
      confirmed after amplification and sequence analysis of fungal internal
      transcribed spacers 1 and 2 and 5.8S ribosomal DNA regions. Surgery and
      antifungal treatment with oral itraconazole associated with flucytosine allowed
      apparent cure after a 10-month follow-up. Envenomation with pine processionary
      caterpillars (Thaumetopoea pityocampa) and subsequently intensive corticotherapy
      were considered as possible predisposing factors. This is, to the best of our
      knowledge, the first case in which C. bantiana is identified as the causative
      agent of eumycetoma.

PMID- 15472376
TI  - Gemella bergeriae endocarditis diagnosed by sequencing of rRNA genes in heart
      valve tissue.
AB  - We describe a case of Gemella bergeriae endocarditis in a patient with a bicuspid
      aortic valve. Diagnosis was confirmed by sequencing of 16S rRNA genes in heart
      valve tissue. This is the first report of Gemella endocarditis confirmed by
      molecular detection of bacterial genes in heart valve tissue.

PMID- 15472378
TI  - Detection of Bartonella quintana by direct immunofluorescence examination of
      blood smears of a patient with acute trench fever.
AB  - We report a case of Bartonella quintana acute symptomatic infection in a homeless
      man, presenting as a typical trench fever. B. quintana has been retrieved in
      erythrocytes in large clusters and in erythroblasts. Direct immunofluorescence of
      blood smears allows a rapid diagnosis.

PMID- 15472379
TI  - Disseminated infection with Prototheca zopfii after unrelated stem cell
      transplantation for leukemia.
AB  - Disseminated infection with Prototheca zopfii is a rare disease in
      immunosuppressed patients. We here report the first case of lethal infection with
      P. zopfii following unrelated stem cell transplantation for leukemia.
      Breakthrough protothecosis occurred during long-term administration of
      voriconazole in the case of pulmonary aspergillosis.

PMID- 15472380
TI  - Vibrio metschnikovii, a rare cause of wound infection.
AB  - We report the first case of a postoperative wound infection caused by Vibrio
      metschnikovii on the lower right leg of a patient after saphenectomy. Compared to
      the healing of an uninfected site, that of the right leg was delayed, and a cure
      was achieved by intensified wound care. Several swabs taken from the infected
      site grew a gram-negative rod in pure culture that was identified as V.
      metschnikovii by the VITEK 2 system. The source of the infection was not
      detected; however, the absence of putative risk factors (exposure to water or
      shellfish or an episode of diarrhea), the profession of the patient (butcher),
      and the isolation of V. metschnikovii in a variety of farm animals (chicken,
      cattle, swine, and horses) suggest that infections caused by V. metschnikovii may
      be regarded as zoonotic.

PMID- 15472381
TI  - Novel observations of genotypic and metabolic characteristics of three subspecies
      of Streptococcus gallolyticus.

PMID- 15472383
TI  - Proceedings of the 2nd International Conference on New Biomedical Materials, 5-8
      April 2003, Cardiff, Wales, United Kingdom.

PMID- 15472382
TI  - Need for procedural details in detection of periodontopathic bacterial DNA in the
      atheromatous plaque by PCR.

PMID- 15472384
TI  - Copolymers of 2-methacryloyloxyethyl phosphorylcholine (MPC) as biomaterials.
AB  - Copolymers of 2-methacryloyloxyethyl phosphorylcholine (MPC) showed good
      hemocompatibility as hypothesized. The hypothesis was surfaces having
      phosphorylcholine groups by polymerization of MPC could accumulate phospholipids
      from blood stream and show good blood compatibility. We designed and prepared a
      methacylate having a phosphorylcholine group. While it was possible to introduce
      them by polymer reactions, polymer reaction is not always good method to prepare
      the desired pure surface. This must be very important point to consider
      biomaterials, as we have to apply them in our body without any adverse effects.
      The hypothesis was confirmed by changing copolymer composition. The adsorption
      amount of phospholipids on the surfaces increased with increasing the MPC units
      in the copolymers. On the other hand, increasing MPC units in MPC copolymers
      decreased adsorption amount of peptides. There is limitation in blood
      compatibility tests in vitro due to unstable characteristics of blood itself. We
      evaluated them with series of blood compatibility tests, in vitro, ex vivo and in
      vivo, on coated PMMA beads, modified hollow fibers for hemodialysis and 2 mm
      small diameter blood vessels, respectively. These data suggested MPC is a
      promising methacrylate to develop good blood contacting devises, which may not
      require systemic anticoagulation. Conventional blood compatible biomaterials were
      not suitable to make permeable membranes. But MPC is soluble in water and we
      could prepare permeable membranes to various solutes by the copolymerization.
      Introduction of MPC copolymers on cellulose and polysulfone hollow fiber
      membranes gave them nonthrombogenicity but it did not give adverse effect on
      their permeability. These data suggested that it is possible to apply them to
      hemodialyzers, oxygenators and percutaneous glucose sensors to keep diabetic
      patients easier. MPC surfaces are good hydrogel to minimize damage on tissues by
      lubricating between organs and the coated devices. They do not induce
      denaturation of peptides, which is beneficial to keep activities of enzymes
      longer. And poly-MPC dissolved is applicable to stabilize several bioactive
      peptides in aqueous phase. So MPC polymers are useful to minimize fouling by
      inhibiting the adsorption of bioactive proteins. MPC has high potential to
      develop many varieties of new biomaterials useful in so-called biotechnology. MPC
      and their copolymers are commercially available from NOF (Tokyo, Japan) and
      Biocompatibles (UK, as PC technology).

PMID- 15472385
TI  - Drug loading and elution from a phosphorylcholine polymer-coated coronary stent
      does not affect long-term stability of the coating in vivo.
AB  - A drug eluting coronary stent was developed for use in preclinical and clinical
      trial evaluation. The stent was coated with a phosphorylcholine (PC)-based
      polymer coating containing the cell migration inhibitor batimastat. A
      pharmacokinetic study was conducted in a rabbit iliac model using (14)C
      radiolabeled version of the drug; this showed the drug release to be first order
      with 94% of it being released within 28 days. Unloaded and drug-loaded stents
      were implanted in a porcine coronary artery model; a number were explanted at 5
      days and scanning electron microscopy was used to show that the presence of the
      drug did not affect the rate of stent endothelialization. The remainder of the
      stents were removed after 6 months and the stents carefully removed from the
      arterial tissue. Fourier-transform infrared (FT-IR) spectroscopy (both attenuated
      total reflectance and microscopic imaging) was used to show the presence of the
      PC coating on control unloaded, drug-loaded and explanted stents, providing
      evidence that the coating was still present. This was further confirmed by use of
      atomic force microscopy (AFM) amplitude-phase, distance (a-p,d) curves which
      generated the characteristic traces of the PC coating. Further AFM depth
      profiling techniques found that the thicknesses of the PC coatings on an control
      unloaded stent was 252+/-19 nm, on an control batimastat-loaded stent 906+/-224
      nm and on an explanted stent 405+/-224 nm. The increase in thickness after the
      drug-loading process was a consequence of drug incorporation in the film, and the
      return to the unloaded dimensions for the explanted sample indicative of elution
      of the drug from the coating. The drug delivery PC coating was therefore found to
      be stable following elution of the drug and after 6 months implantation in vivo.

PMID- 15472386
TI  - Effect of binder additives on terbutaline hydrogels of alpha-PVA/NaCl/H(2)O
      system in drug delivery: I. Effect of gelatin and soluble starch.
AB  - In order to prepare ecologically and biologically safety physical cross-linked
      hydrogel of a-PVA/NaCl/H(2)O system, we prepared blend hydrogel of natural
      polymeric binders like gelatin and starch in above system, and effect of these
      binder additives were evaluated on terbutaline release kinetics. Terbutaline (1%)
      hydrogels of a-PVA(7%)/NaCl(11%)/H(2)O and a-PVA(7%)/H(2)O system (Cyclic FT
      process) were prepared along with various concentrations of gelatin and soluble
      starch by feed-mixture dissolving method. In case of a-PVA/NaCl/H(2)O system only
      one cycle gelation was done at -20 degrees C for 24 h. On the other hand 3 cycles
      were done by freezing at -30 degrees C for 16 h followed by thawing at room
      temperature for 8 h. Drug release was done by paddle method (USP type II) with a
      rotation of 50 rpm at 37 degrees C in distilled water. Swelling of the gel was
      done at 37 degrees C for 45 h and melting temperatures of the gel were also
      studied using the upside-down test tube method. Comparatively lower values of
      release rate, diffusion coefficient and kinetic constant were found from the
      blend hydrogel of a-PVA/starch/NaCl/H(2)O system. When % cumulative release was
      plotted vs. square root of time it showed straight lines, which indicated Higuchi
      Matrix Dissolution Model. Inclusion of starch binder increased the degree of
      swelling compared with that of gelatin. 15 h was found as equilibrium swelling
      time. A Fickian swelling of this blend hydrogel system indicated the swelling
      controlled Fickian diffusion type of drug release. Melting temperatures of the
      blend hydrogels were characteristically higher (94-95 degrees C) than that of
      cyclic FT (72-76 degrees C), resulting a thermostable hydrogel for biological
      system. SEM morphological studies of gel surface indicated the well-developed
      interpenetrating macromolecular network structure like fish net in starch blend
      gel prevails over other hydrogel studied here. Gelatin has got characteristic
      tunnel (200 microm in diameter) inside the macromolecular network that
      contributes this system higher release kinetics than that of starch.

PMID- 15472387
TI  - Flexible coils with a drug-releasing hydrophilic coating: a new platform for
      controlled delivery of drugs to the eye?
AB  - Delivery of drugs to the front-side of the eye is routinely done through eye
      drops. It is known that approximately 80% of each eye-drop is lost, as a result
      of rapid clearance of the tear fluid via the naso-lacrymal canal. Consequently,
      repeated administration through several droplets is usually necessary to achieve
      a desired effect, e.g., mydriasis (widening of the pupil) prior to corneal
      surgery. Studies with a new ocular drug delivery device are reported. The new
      device is believed to provide a basis for more convenient and efficient method
      for ocular drug delivery. The device is a metallic coil with a hydrophilic, drug
      containing polymeric coating. The coil is placed in the conjunctival fornix
      (under the lower eye-lid), and the drug is released slowly, by diffusion into the
      tear fluid. The capacity of the device could be increased by using the lumen of
      the coils as a depot for the drug to be released. Preliminary experiments with
      the new device are reported. These experiments were performed largely in vitro,
      but partly also in vivo. The latter experiments comprised release of the
      fluorescent dye, and delivery of atropine (a potent mydriatic agent), in the eyes
      of several healthy volunteers. The first results obtained with the new device
      indicate its potential utility. It is discussed that much more research and
      development work is required, e.g., to define the optimal design of the coil in
      order to minimise the risk for irritation. Furthermore, the parameters that
      define the kinetics of the intraocular drug release must be defined and optimised
      with respect to the exact application.

PMID- 15472388
TI  - Intraocular lenses, bacterial adhesion and endophthalmitis prevention: a review.
AB  - Postoperative endophthalmitis following intraocular lens (IOL) implantation is
      still one of the most feared complications of cataract surgery. Bacterial
      adhesion to IOLs during their insertion is a prominent etiological factor.
      Polypropylene was the first biomaterial that allowed this relation of cause and
      effect to be proven. Following adhesion, bacteria replicate, congregate and form
      multiple layers of microcolonies which actually represent the basic structural
      unit of the biofilm. The bacteria are embedded in a slime layer. Personal
      photographs illustrate the different steps of biofilm formation. This slime
      matrix is not only an adhesive medium; it also affects virulence. Adhesion to
      IOLs has been studied by several in vitro studies and discrepancies can be found
      between them which are due to variations of experimental conditions. The strains,
      the incubation times and the methods all varied. Adhesion is affected by the
      nature of the IOLs, the isolates and the surrounding medium. Since this medium is
      very difficult to model because of its complexity, in vivo studies seemed
      essential. We have recently determined in vivo evolution of the amount of
      attached bacteria to five types of IOLs. Crystalline lenses from 90 domestic pigs
      were removed aseptically and replaced with previously infected IOLs. There have
      been few epidemiological studies published to determine the relationship between
      endophthalmitis and the IOL type. However, the perfect biomaterial that could
      prevent postoperative endophthalmitis does not yet exist. Globally, hydrophilic
      materials and hydrophobic acrylic seem to be less sticky than silicone or PMMA,
      but this remains to be proven clinically.

PMID- 15472389
TI  - Methyl-DEAE-dextran: a candidate biomaterial.
AB  - The full quaternisation of DEAE-dextran was successfully attempted and an
      application of the quaternised product was suggested. Commercial DEAE-dextran was
      reacted with iodomethane at 60 degrees C in the presence of NaOH. The raw product
      was purified by dialysis, during which the iodide ion was replaced by chloride. N
      methylation and O-methylation resulted from the reaction. A second methylation
      step produced no further changes in the molecule. Alkalimetry indicated the
      absence of amino groups in the methylated polymer molecule, thus testifying to a
      complete quaternisation. N-acetylcysteine (AcCy) was neutralised with the polymer
      in the hydroxide form, thus obtaining the methyl DEAE-dextran salt of AcCy (Me
      DEAE-dextran/AcCy), whereby an ophthalmic formulation for the treatment of the
      dry eye syndrome was prepared. For comparison, the neutral AcCy salt of
      commercial DEAE-dextran (DEAE-dextran/AcCy) was prepared. The AcCy content in Me
      DEAE-dextran/AcCy was higher than in DEAE-dextran/AcCy (23 vs 13%), while the
      viscosity of a solution containing the salt concentration corresponding to the
      therapeutic AcCy concentration (4%w/v) was lower with the former compared to the
      latter salt (20.5 vs 23.9 mPa s). Both solutions were ipotonic (245 mOsm/kg),
      whereas the commercial Tirocular is strongly hypertonic (900 mOsm/kg) and
      irritant.

PMID- 15472390
TI  - Ultrathin polymer monolayers for promotion of cell growth on bioprosthetic
      materials -- evolution of a new concept to improve long term performance of
      biologic heart vales.
AB  - Reoperation of aldehyde tanned bioprotheses due to calcific degeneration remains
      their major drawback. Based on experiments studying mechanisms and factors that
      influence the time phase, extent and progression of calcification and evaluating
      the efficiency of anticalcification treatments and the effects of surface seeding
      with vital cells a new concept to avoid calcification emerged: masking aldehyde
      residues with a covalently bound polymer that supports surface cell seeding.
      Different covalently bound polymers were tested for their suitability to grow
      cells. Dense cell growth was achieved on some polymers but without correlation to
      physico-chemical properties. Ultrathin coating of biological materials appears a
      promising approach to achieve lining with vital cells.

PMID- 15472391
TI  - Design of novel biointerfaces (I). Blood compatibility of poly(2-methoxyethyl
      acrylate).
AB  - We have reported that poly(2-methoxyethyl acrylate) (PMEA) shows excellent blood
      compatibility with respect to the coagulation, complement, leukocyte and platelet
      systems in vitro and ex vivo when compared with other polymer surfaces. In this
      study, to clarify the reasons for this good compatibility, the structure of water
      in the hydrated PMEA were investigated and compared to water structure of poly(2
      hydroxyethyl methacrylate) (PHEMA) and polyacrylate analogs as references. The
      hydrated water in PMEA could be classified into three types; free water, freezing
      bound water, and non-freezing water. Cold crystallization of water in the heating
      process was clearly observed at -42 degrees C. This cold crystallization is
      interpreted as the phase transition from the amorphous ice to the crystal ice
      that belongs to the freezing-bound water in PMEA. On the other hand, the cold
      crystallization peak (freezing bound water; which prevents the biocomponents from
      contacting the polymer surface or non-freezing water on the polymer surface) was
      not observed for hydrated PHEMA and PMEA analogous polymers. We hypothesized that
      the freezing-bound water layer between free water and non-freezing water was an
      important factor for the excellent blood compatibility of PMEA.

PMID- 15472392
TI  - Design of novel biointerfaces (II). Fabrication of self-organized porous polymer
      film with highly uniform pores.
AB  - Application of porous polymer materials to novel bio-interfaces for tissue
      engineering scaffold and artificial organs including blood filters, dialyzer, and
      oxygenator membranes have been in progress. The present study describes the
      fabrication and characterization of self-organized highly regular porous polymer
      films with uniform pore sizes are prepared by simple casting technique. Various
      fabrication parameters affecting the pore size such as polymer concentration,
      boiling point of solvent, cast volume and substrate are studied. The pore size
      can be controlled in the range from 1 to 50 microm by changing the evaporation
      rate of the polymer solutions. The porous film with uniform pore size is used for
      tissue engineering scaffold and cell separation membrane. To simulate the
      leukocyte eliminating from human blood, the porous film was attached to a module.
      The films with 5-9 microm pores provided the complete selectivity of separation
      for the leukocyte from the whole blood. The leukocyte elimination ratio depends
      on pore structures (size and depth) as well as recovery of platelet and
      erythrocyte.

PMID- 15472393
TI  - The use of hydrophobins to functionalize surfaces.
AB  - The physiochemical nature of surfaces can be changed by small proteins which are
      secreted by filamentous fungi. These proteins, called hydrophobins, are
      characterized by the presence of eight conserved cysteine residues and a typical
      hydropathy pattern. Upon contact with a hydrophilic-hydrophobic interface they
      self-assemble into highly insoluble amphipathic membranes. As a result,
      hydrophobic surfaces become hydrophilic and vice versa. Genetic engineering of
      hydrophobins was used to study structure-function relationships. In addition,
      engineered hydrophobins were constructed to increase the biocompatibility of
      surfaces. The glycosylated N-terminal region of the mature SC3 hydrophobin was
      deleted and the cell-binding domain of human fibronectin was introduced at the N
      terminus. The gross properties of the hydrophobins were not affected. However,
      the physiochemical properties of the hydrophilic side of the assembled protein
      did change. Growth of fibroblasts on Teflon could be improved by coating the
      solid with the engineered hydrophobins. Thus, by changing the N-terminal part of
      hydrophobins, the physiochemical nature of the hydrophilic side of the assembled
      form can be altered and a variety of new functionalities introduced. The fact
      that hydrophobins self-assemble at any hydrophilic-hydrophobic interface,
      irrespective of the chemical nature of the surface, therefore provides a generic
      approach to modify surfaces and make them interesting candidates for the use in
      various technical and medical applications.

PMID- 15472394
TI  - The potential of biosensor technology in clinical monitoring and experimental
      research.
AB  - Glucose or lactate biosensors are very useful for monitoring metabolism.
      Continuous monitoring of glucose is for example very important in diabetic
      patients. The measurement of lactate, a marker for oxygen deficiency, is used in
      the intensive care unit to monitor the patients' condition. In our laboratory we
      have developed two types of on-line biosensors to measure in vivo glucose and
      lactate: a sandwich-type biosensor and, very recently, a miniaturized flow
      through biosensor. These biosensors are not placed in the body itself, but are
      connected to implanted microdialysis or ultrafiltration probes. Both types of
      biosensors are based on the oxidation of substrate using glucose oxidase or
      lactate oxidase and electrochemical detection. In the sandwich-type sensor, the
      enzymes are physically immobilized between two cellulose nitrate filters, and
      operate with ferrocene as a mediator. In the miniaturized biosensor, with an
      internal volume of 10-20 nanolitres, the enzymes are immobilized on the electrode
      via in situ encapsulation in poly(1,3-phenylenediamine). In this review we shall
      explain the working of these biosensors, and describe their application in
      clinical monitoring and experimental research.

PMID- 15472395
TI  - Binary CaO-SiO(2) gel-glasses for biomedical applications.
AB  - Bioactive materials are routinely used in dental and orthopaedic applications.
      The concept was first introduced in 1971, with the discovery of 45S5 Bioglass,
      which is known to develop an interfacial bond between the implant and the host
      tissue. This glass is composed of SiO(2), CaO, P(2)O(5) and Na(2)O. Since then
      numerous glasses and glass ceramics with similar compositions have been
      extensively studied for clinical applications. Until 1990 it was accepted that
      P(2)O(5) and Na(2)O were necessary components for the glass composition to be
      bioactive. However, calcium silicate glasses with high SiO(2) content are
      impossible to produce using the traditional melt-quench method. This is due to
      the liquid-liquid immiscibility region that is present between 0.02 and 0.3 mole
      fraction of CaO and in terms of bioactivity, high CaO compositions were inferior
      to those quaternary bioactive glass compositions already in existence. In the
      last few years several studies have been reported regarding the production of CaO
      SiO(2) glasses via the sol-gel processing technique. This report summarises the
      findings of the past and the present and also outlines potential of these calcium
      silicate gel-glasses in the field of biomaterials.

PMID- 15472396
TI  - Injection biomechanics of bone cements used in vertebroplasty.
AB  - The incidence of osteoporotic bone fractures is growing exponentially as the
      western population ages and as life expectancy increases. Vertebroplasty, where
      acrylic or calcium phosphate cement is injected into the weakened vertebrae to
      augment them, is an emerging procedure for treating spinal fragility fractures.
      However, cement injection is currently limited because there are no clear
      standards for a safe, reproducible and predictable procedure. The purpose of this
      paper is to examine the role that bone cements play in the underlying bio
      mechanisms that affect the outcomes of cement injection. Our most important
      finding after combining clinical, laboratory and theoretical research is that the
      process of cement injection poses conflicting demands on bone cements. The
      cements are required to be more viscous and less viscous at the same time. The
      challenge therefore is to develop biomaterials, techniques and/or devices that
      can overcome or manage the conflicting demands on cement viscosity.

PMID- 15472397
TI  - A study of polyvinyl alcohol-hydrogel (PVA-H) artificial meniscus in vivo.
AB  - The importance of knee meniscus function is now recognized, and the treatment of
      meniscus injury has been changing from resection to repair. However, depending on
      the type of injury, meniscectomy sometimes cannot be avoided. In such case, it is
      important to anticipate the future problem of degenerative change or
      osteoarthrosis in knee joint. In future, auto-graph using regenerative meniscus
      will be developed by tissue engineering. However, even if it will be possible,
      considering the healing period, the young athlete with severe meniscus injury may
      select meniscectomy in order to return to sports life as early as possible
      avoiding the long immobilization or declining sports skill. In consideration of
      the prognosis and circumstances in such patients, we need a artificial meniscus
      for salvage. To assess further the use of polyvinyl alcohol-hydrogel (PVA-H)
      artificial meniscus, we performed some mechanical tests about PVA-H and animal
      experiment. In mechanical tests, we found that a high water content PVA-H showed
      viscoelastic behaviour similar to that of human meniscus. Moreover, the
      frictional coefficient of PVA-H against natural articular cartilage was also
      effective. In the animal experiment using rabbits, the lateral meniscus was
      replaced with an artificial meniscus in one knee side and lateral meniscectomy
      was performed in another knee side of each rabbit. We have already reported the
      results up to 1 year after operation, present study investigated the results in
      postoperative 1.5 years. In the results, the articular cartilage state of knee
      joint implanted PVA-H meniscus was good even after 1.5 years, while OA change
      progressed in meniscectomy knee joint. In addition, neither wear nor breakage of
      PVA-H was observed. These results proved that an artificial meniscus using a high
      water content PVA-H can compensate for meniscal function and might be clinically
      applicable.

PMID- 15472398
TI  - Bioabsorbable self-reinforced plates and screws in craniomaxillofacial surgery.
AB  - Bioabsorbable fixation devices have been used in craniomaxillofacial (CMF)
      surgery since the early 70's. In our departments the experimental use started in
      the 80's with self-reinforced (SR) polylactide devices. The first clinical
      operations were carried out in 1991. Since that time, we have used different
      types of self-reinforced bioabsorbable devices in the fixation of several
      hundreds of osteotomies and fractures. Patients' acceptance has been generally
      excellent and very few complications occurred during this follow-up of over 10
      years. The complications have been minor and have not affected the end results of
      the operations. In only one oncologic patient, the devices needed to be removed
      and replaced with a rigid reconstruction plate. The minor complications consisted
      mainly of a few infections, dehiscence of the wound and plate exposure together
      with granulation tissue in the operation field. No implant-specific complications
      were recorded. However, there is a learning curve for the surgeon, as there is
      with all new methods introduced. Based on our experience, self-reinforced
      bioabsorbable devices are safe to be used in several indications in the
      craniomaxillofacial skeleton, also in load-shearing situations.

PMID- 15472399
TI  - Effect of calcium and phosphorus ion implantation on the corrosion resistance and
      biocompatibility of titanium.
AB  - This paper is concerned with the corrosion resistance and biocompatibility of
      titanium after surface modification by the ion implantation of calcium or
      phosphorus or calcium + phosphorus. Calcium and phosphorus ions were implanted in
      a dose of 10(17) ions/cm(2). The ion beam energy was 25 keV. The microstructure
      of the implanted layers was examined by TEM. The chemical composition of the
      surface layers was determined by XPS and SIMS. The corrosion resistance was
      examined by electrochemical methods in a simulated body fluid (SBF) at a
      temperature of 37 degrees C. The biocompatibility was evaluated in vitro. As
      shown by TEM results, the surface layers formed during calcium, phosphorus and
      calcium + phosphorus implantation were amorphous. The results of the
      electrochemical examinations (Stern's method) indicate that the calcium,
      phosphorus and calcium + phosphorus implantation into the surface of titanium
      increases its corrosion resistance in stationary conditions after short- and long
      term exposures in SBF. Potentiodynamic tests show that the calcium-implanted
      samples undergo pitting corrosion during anodic polarisation. The breakdown
      potentials measured are high (2.5 to 3 V). The good biocompatibility of all the
      investigated materials was confirmed under the specific conditions of the applied
      examination, although, in the case of calcium implanted titanium it was not as
      good as that of non-implanted titanium.

PMID- 15472400
TI  - The initial attachment and subsequent behavior of osteoblastic cells and oral
      epithelial cells on titanium.
AB  - The interaction between implant materials and bone cells or oral epithelial (OE)
      cells contributes to the clinical success of dental implants. The functional
      activity of cells in contact with an implant is determined by its surface
      properties. Before cells attach, extracellular matrix (ECM) in the serum deposits
      on the substrate; rounded cells then attach and spread upon it. Cells form focal
      adhesions and polarize, then start to migrate or proliferate to form colonies.
      Comparison of the attachment and behavior of osteoblastic cells on titanium (Ti)
      and hydroxyapatite (HA) revealed that more cells attached on HA and that these
      spread more rapidly than on Ti. In contrast, cells did not form good stress
      fibers or vinculin-positive focal adhesions on HA, whereas the cells on Ti
      possessed well-defined and polarized stress fibers. The initial attachment of OE
      cells to Ti was inferior to that on polystyrene culture dish or glass, and the OE
      cell migration area, indicated by the deposition of LN5, was smaller on Ti than
      on the other materials. This review summarizes data on the attachment and
      behavior of osteoblastic cells and OE cells on biomaterials, which may suggest
      future improvements in surface properties.

PMID- 15472401
TI  - Kinetic study of the expression of beta-catenin, actin and vinculin during
      osteoblastic adhesion on grooved titanium substrates.
AB  - Intercellular adhesions are known to play an important role in differentiation of
      osteoblasts and in the development of bone tissue architecture. However, to our
      knowledge, they have never been studied during the formation of bone tissue in
      contact with a biomaterial surface. In an in vitro kinetic study, we followed the
      expression of proteins involved in cell-cell interactions (beta-catenin), in cell
      material interactions (vinculin) and in cytoskeleton (actin) of human
      osteoblastic cells cultured on grooved titanium-based substrates during 1, 2, 4,
      6, 24, 48, and 72 hours. The human osteoblasts aligned themselves in the 150
      microm wide grooves only after 24 hours. The distribution of vinculin-positive
      focal contacts, actin cytoskeleton and beta-catenin positive-adherens junctions
      was not significantly influenced by the cell alignment. beta-catenin-positive
      adherens junctions were expressed by human osteoblasts as soon as 1 hour after
      inoculation. At this time, they showed a patch-like aspect along cytoplasmic
      processes in contact with an underlying or an adjacent cell. After 2 hours, the
      patches were more and more numerous underlining the connections between cells.
      After 4 hours and more, the patches were organised in a parallel arrangement
      perpendicular to the two connected cells forming a "zip-like" aspect.
      Additionally, using double immuno-staining, we demonstrated that sometimes beta
      catenin and vinculin appeared co-localised and sometimes not. The linkage of
      catenin/cadherin complex and vinculin-positive focal contacts with actin
      filaments may explain this apparent co-localisation.

PMID- 15472402
TI  - Mechanism of adsorption of mucin to titanium in vitro.
AB  - Mucin is the main salivary protein in the mouth of animals including man. The
      present study aims at investigating the role of electrostatic interactions in the
      adsorption of mucin to titanium in vitro. The binding profile of mucin to
      titanium was analyzed according to an adsorption isotherm. Mucin was dissolved
      and the solution suspended with native, calcium, magnesium, or potassium treated
      commercially pure Ti powder, at pH 3.0 and 7.4. The amount of unabsorbed protein
      in the supernatant fluid was measured. The maximum amount of adsorbed mucin was
      0.11 mg/1.0 g of Ti. The mucin-Ti association constant was estimated to be 2.91
      ml/mg. Pretreatment of Ti with calcium, or magnesium alone, or combined resulted
      in increased adsorption of mucin to Ti. No increase in adsorption was recorded
      following pretreatment of Ti with potassium. The results indicate the involvement
      of electrostatic interactions in the absorption of mucin to Ti.

PMID- 15472403
TI  - Zinc ion release from novel hard tissue biomaterials.
AB  - Zinc polyalkenoate cements (ZPCs) and glass polyalkenoate cements (GPCs) are used
      routinely in dentistry, but have potential for orthopaedic applications as they
      set at body temperature without shrinkage or significant heat evolution. However,
      the materials have drawbacks; ZPCs are biocompatible in implant studies, but a
      fibrous collagen capsular layer forms adjacent to the cement. GPCs are bioactive
      in the bone environment as a result of the release of calcium, phosphate and
      fluoride ions, as well as the formation of a silicious gel phase, but research
      has shown that aluminum ions released result in defective bone mineralisation and
      as a consequence the ability of these cements to chemically bond to bone is lost.
      Two approaches have been developed to overcome these problems. The ZPC route
      considers a ZnO : hydroxyapatite (HA) : poly(acrylic acid) (PAA) mixture, the HA
      incorporated to improve bioactivity. The GPC route employs a calcium zinc
      silicate glass; the zinc taking the role that aluminum plays in conventional
      GPCs. This study has shown that cements can be formulated by an acid base
      reaction between PAA and both calcium zinc silicate glasses (GPCs) and a mixture
      of hydroxyapatite and zinc oxide (ZPCs). The moduli of these cements are
      comparable to both bone and conventional acrylic cements, highlighting their
      potential for biomedical applications. Unfortunately, both materials have
      previously been shown to be toxic by cell culture methods, as a result of high
      zinc ion release, and so it is necessary to study ion release profiles of the
      cements in order to determine the magnitude of this release. Considering the
      ZPCs, the modulus of the cement has an inversely proportional relationship to the
      zinc ion release. From the data presented it is clear that increases in polymer
      concentration results in lower amounts of zinc ions being released, whilst molar
      mass of the PAA has no influence. Therefore it would appear that polymer
      concentration has a significant influence over ion release. Generally, the amount
      of Zn(2+) released decreases with increasing HA content and/or decreasing ZnO
      content. Considering the GPCs, the materials are all seen to release large
      amounts of the active ion, when compared to the commercial versions. The extent
      of this release increases with temperature and agitation. The release could be
      minimised by an increased P : L mixing ratio, and an increased PAA concentration,
      which would produce a more cross-linked cement matrix. Minimising the release of
      the active ion should improve the in vitro bioactivity of both materials.
      However, for a full understanding of the clinical benefits of such materials, an
      in vivo study would be required.

PMID- 15472404
TI  - Nanocrystalline hydroxyapatite-polyaspartate composites.
AB  - The direct synthesis of hydroxyapatite-poly-L-aspartic acid (HA-PASP)
      nanocrystals has been carried out in presence of increasing amounts of PASP in
      solution up to 56 mmol/l. WAXS, TEM, TGA, IR and chemical analyses were used to
      characterize the structure, morphology and composition of the products. PASP is
      quantitatively incorporated into HA crystals, provoking a reduction of the
      coherent length of the crystalline domains. Furthermore, composite crystals
      display a greater length/width ratio with respect to the control HA crystals, and
      show a remarkable trend towards aggregation. The broadening of the X-ray
      diffraction reflections indicate a reduction of the coherent length along the
      long dimension 002 and the cross section 310 of the apatite crystals. The
      comparison between the morphological and structural data allows to suggest a
      specific interaction between PASP and HA structure.

PMID- 15472405
TI  - Investigations on the synthesis and crystallization of hydroxyapatite at low
      temperature.
AB  - An easy method to crystallize homogenous HAP at physiological pH as well as
      powders of HAP and CPP at low temperature are described. Platy and spherulitic
      crystals of HAP were crystallized at the physiological pH using single diffusion
      method. Well-defined platy crystals of hydroxyapatite were obtained at the
      physiological temperature and pH. These crystals were found to be pure and
      homogenous form of HAP without any contamination from the crystallizing medium.
      Spherulitic crystals of HAP of approximately 3 mm in diameter were obtained in
      the presence of Fe at 47 degrees C. A sol-gel technique involving agarose is
      described for the preparation of hydroxyapatite and calcium pyrophosphate. Pure
      form of HAP was synthesised at 85 degrees C and its sintering properties were
      also studied. At a temperature of 1200 degrees C, the material gets completely
      converted to alpha-calcium pyrophosphate. The samples were analysed by XRD, IR,
      TGA and SEM. The particle size of the synthesised powders was measured using the
      dynamic light scattering experiments.

PMID- 15472406
TI  - Prognosticfactors in patients with renal cell carcinoma: is TNM (1997) staging
      relevant in Indian subpopulation?
AB  - BACKGROUND: RCC (Renal Cell Carcinoma) is a common genitourinary malignancy, but
      its behavior has not been studied in the Indian Subpopulation. AIMS: The aim of
      this study was to assess the validity of 1997 AJCC TNM staging in Indian
      subpopulation and also to identify independent predictors for survival in
      patients having RCC. SETTING AND DESIGN: Retrospective uncontrolled analysis of
      patients with RCC was performed at our centre. MATERIAL AND METHODS: Medical
      records of patients of undergoing radical nephrectomy at our center between 1994
      to August 2003 were identified retrospectively. Medical records of 178 patients
      were available for analysis. Patient characteristics, preoperative imaging and
      surgical details were reviewed. Each tumor was staged according to the 1997 AJCC
      TNM classification. Nuclear grade was assigned according to the Fuhrman's grading
      system. STATISTICAL METHODS: Statistical analysis was performed using statistical
      software and descriptive statistics and survival functions were obtained.
      Univariate and multivariate analysis of factors affecting outcome of the patient
      were performed. RESULTS: Mean follow up period was 42.3 months (range 3 to 108
      months). Stage wise 5-year Cancer specific survival was 87.2% in stage 1 disease,
      74.3% in stage 2, 36.4% in stage 3 and 3.1% in stage 4. Univariate analysis
      revealed that stage, grade and lymph node status were statistically significant
      (P=0.009, 0.007 and 0.003 respectively). Sub-classifying stage 1 tumors between
      tumor of less than 4 cm. and more than 4 cm. did not reveal any statistically
      significant difference in survival (P=0.32). Multivariate analysis model revealed
      that Fuhrman's grade and lymph node status were statistically significant
      (P=0.007 and 0.002 respectively). CONCLUSION: This study validates the TNM (1997)
      staging for RCC as having significant survival impact in the Indian
      subpopulation. Sub-classifying stage 1 tumors between tumor of less than 4 cm.
      and more than 4 cm is not of much importance. Nuclear grade and lymph node
      involvement are important independent predictors of survival. Organ confined
      tumors with high nuclear grades need to be followed up more rigorously.

PMID- 15472407
TI  - Why is high grade squamous intraepithelial neoplasia under-diagnosed on cytology
      in a quarter of cases? Analysis of smear characteristics in discrepant cases.
AB  - BACKGROUND: The accuracy of cervical cytology has been questioned due to high
      false negative rate. In order to improve the sensitivity of cytology it is
      prudent to analyze the factors which hamper with the diagnosis of high grade
      lesions. AIMS: To study the cyto-histologic agreement in High grade squamous
      intraepithelial lesions (HSIL) of uterine cervix and to analyze the smear
      characteristics in discrepant cases. SETTINGS AND DESIGN: Cervical smears of 100
      histology proven cases of Cervical intraepithelial neoplasia III (CIN III) were
      retrieved and reviewed to study cyto-histologic agreement in the diagnosis of
      high grade lesions. The discrepant smears, undercalled on cytology, were further
      analyzed to determine the reasons for misinterpretations. Statistical analysis
      was performed to find out any significant factors for discrepancies. RESULTS:
      Cytology was able to correctly identify 74 HSILs while in 26 cases a diagnosis of
      Low grade squamous intraepithelial lesions (LSIL) or below was given. On review,
      16 of these non correlating cases could be reclassified as HSIL on cytology while
      in 10 the diagnosis of LSIL or less persisted. 12/16 (75%) discrepant cases,
      reclassified as HSIL represented interpretive errors. Sampling errors (7/10) and
      air drying (5/10) were more frequent in under diagnosed cases. The statistical
      analysis did not yield any significant differences in the two review groups.
      CONCLUSION: 26% of HSIL cases were underdiagnosed on cervical smears. The major
      confounding factors responsible for under interpretation on cytology included air
      drying artifacts and metaplastic maturation of abnormal cells.

PMID- 15472408
TI  - Pelvic exenteration: a perspective from a regional cancer center in India.
AB  - BACKGROUND: Pelvic exenteration is an extensive surgical procedure performed for
      locally advanced cancers in the pelvis. AIMS: The twenty-year experience with
      this procedure at the Cancer Institute has been analyzed for morbidity, failure
      pattern and survival. SETTINGS AND DESIGN: The case records of all the patients
      who had undergone pelvic exenteration between 1981 and 2000 at Cancer Institute
      (WIA), Chennai were retrieved from Tumor Registry and were analyzed. METHODS AND
      MATERIAL: Forty-eight patients underwent Pelvic Exenteration from 1981 to 2000 at
      the institute. Twenty-nine of them had rectal cancer, 15 had cervical cancer, 3
      had bladder cancer, and 1 had ovarian cancer. There were 43 women and 5 men with
      a median age of 45 years. STATISTICAL ANALYSIS: The survival rates were
      calculated by Kaplan-Meier method using EGRET statistical software package.
      RESULTS: The operative mortality and postoperative morbidity were 10.42% and
      62.50% respectively. The 5-year overall survival for the patients with Ca rectum
      and Ca cervix were 54.2% and 77.6% respectively. All 4 patients with Ca bladder
      or Ca ovary survived for more than 5 years. On multivariate analysis, nodal
      involvement and number of positive nodes emerged as significant prognostic
      factors for patients with Ca rectum. Although no factor reached statistical
      significance for patients with Ca cervix, those with adjacent organ invasion had
      a trend towards poorer survival. CONCLUSIONS: For carefully selected locally
      advanced cancer in the pelvis, pelvic exenteration may provide the opportunity of
      long-term survival.

PMID- 15472409
TI  - Polymorphism of GSTM1 and GSTT1 genes in prostate cancer: a study from North
      India.
AB  - BACKGROUND: Glutathione-S-transferases (GSTs) are active in the detoxification of
      wide variety of endogenous or exogenous carcinogens. The genetic polymorphisms of
      GSTM1 and GSTT1 genes have been studied earlier to evaluate the relative risk of
      various cancers. AIM, SETTING AND DESIGN: In the present study, we examined the
      association of the GSTM1 and GSTT1 gene polymorphisms with sporadic prostate
      cancer patients in north Indian population. MATERIAL AND METHODS: This case
      control study was undertaken over a period of 24 months and included 103 prostate
      cancer patients and 117 controls; both patients and controls originated from
      northern part of India. The GSTT1 and GSTM1 genotypes were identified by
      multiplex PCR in peripheral blood DNA samples. STATISTICAL ANALYSIS: Difference
      in genotype prevalence and association between case and control group were
      assessed by the Chi square and Fisher Exact tests. RESULTS: Frequencies of null
      genotypes in GSTT1 and GSTM1, was 11% (13/117) and 30% (35/117) respectively in
      control individuals. The frequencies of GSTT1 and GSTM1 null genotypes in
      prostate cancer patients were 34% (35/103) and 53% (55/103) respectively.
      CONCLUSION: Our study demonstrates that the null genotypes of GSTT1 and GSTM1 are
      substantially at higher risk for prostate carcinoma as compared to the normal
      healthy controls. The GSTT1 and GSTM1 null genotypes did not show significant
      association with tobacco usage in prostate cancer patients. However, the null
      genotypes were significantly stratified in 50-60 year-old patients when incidence
      of prostate cancer is high.

PMID- 15472410
TI  - Patient profile and treatment outcome of rectal cancer patients treated with
      multimodality therapy at a regional cancer center.
AB  - BACKGROUND: Incidence of rectal cancer has wide geographical variation. Disease
      pattern in developing countries is different from developed countries as majority
      of the patients present in advanced stage because of delayed referral and lack of
      uniform treatment practices. AIMS: Present study describes the patient profile
      and treatment results from a tertiary care cancer center in India. SETTING AND
      DESIGN: Tertiary care Regional cancer center. Retrospective analysis 89 patients
      with rectal adenocarcinoma treated between 1995 and 2002 were analyzed. METHODS:
      Patients with adenocarcinoma rectum were evaluated in a G.I. Oncology clinic and
      were treated using multimodality protocols involving surgery, radiotherapy and
      adjuvant chemotherapy. STATISTICAL ANALYSIS: A descriptive analysis of patient
      and disease profile, treatment patterns and out come was performed. Survival
      analysis was performed using Kaplan-Meier method. RESULTS: Mean age of the
      patients was 45.4 years and majority of them had tumor in lower third of rectum
      with evidence of extrarectal spread. Seventy five percent of the patients
      underwent curative resection with abdominoperineal resection being the commonest
      procedure. Forty seven percent of patients were given short course preoperative
      radiotherapy and the remaining received postoperative radiotherapy. Sixty four
      percent of patients could complete planned adjuvant chemotherapy. Operative
      mortality was 2% and 23% had morbidity. Local recurrence rate was 8.9%. 5-year
      disease free and overall survival was 54% and 58% respectively. CONCLUSION:
      Majority of rectal cancer patients present with locally advanced and low rectal
      growths leading to low sphincter salvage rates. Despite the advanced stage of
      presentation optimal oncologic results can be obtained by using a good surgical
      techniques in combination with adjuvant radiotherapy and chemotherapy. Short
      course preoperative radiotherapy seems to be more feasible in Indian context.
      Timely referral and uniform treatment guidelines throughout the country are
      needed for optimal management of rectal cancer in India.

PMID- 15472411
TI  - All-transretinoic acid and chemotherapy in the treatment of acute promyelocytic
      leukemia.
AB  - BACKGROUND: All-transretinoic acid (ATRA) and chemotherapy has improved complete
      remission rates and disease free survival in acute promyelocytic leukemia (APL).
      There is scanty data from Middle East. AIM: To determine the efficacy of ATRA and
      multi-agent combination chemotherapy in treatment of APL in a single Centre in
      Kuwait. SET-UPS AND DESIGN: Tertiary cancer centre, retrospective study. METHODS
      AND MATERIAL: All newly diagnosed APL patients were treated with oral ATRA 45
      mg/m2 daily until complete remission (CR), intravenous daunorubicin 50 mg/m2 on
      days 1,3 and 5, cytosine arabinoside 100 mg/m2 12 hrly on days 1 through 10 and
      etoposide 100 mg/m2 on days 1 through 5. Post remission three courses of
      intensive consolidation chemotherapy were administered. Since October 1999,
      maintenance chemotherapy consisting of oral 6 mercaptopurine 9 mg/m2 daily,
      methotrexate 15 mg/m2 weekly and ATRA 45 mg/m2 for 2 weeks every three months was
      added. Complete remission rates and duration, relapse rate and toxicity were
      studied. RESULTS: 22 of 24 evaluable patients (91.6%) achieved CR. The median
      duration of remission was 13 months (range 2-55 months). Three patients (12.5%)
      relapsed. Two patients (8.3%) developed retinoic acid syndrome and responded to
      dexamethasone. Five patients (20.8%) died one each of refractory disease, during
      remission induction and of relapse. Two patients died while in remission.
      CONCLUSION: ATRA and combination chemotherapy results in high complete remission
      rates and low relapse rate in newly diagnosed APL. Maintenance therapy may be
      useful in preventing relapses.

PMID- 15472412
TI  - Giant cystosarcoma phyllodes tumor of prostate: case report of a rare entity.
AB  - Although glandular and stromal proliferations of prostate are very common in
      adult men, neoplastic proliferations of prostatic stroma are distinctly uncommon.
      These tumors are now grouped as Prostatic Stromal Proliferations of Uncertain
      Malignant Potential (PSPUMP). Phyllodes tumor of the prostate is a rare neoplasm
      in this group with cellular, sarcomatoid stroma and benign hyperplastic glands.
      It is a locally expansile tumor with clinical course varying from benign to
      aggressive. We report a case of a 45-year-old man presented with retention of
      urine and abdominal lump. On laparotomy it was a huge tumor of 4 kg and was
      histologicaly characterized by cellular pleomorphic stroma and hyperplastic
      epithelium. Immunohistochemistry demonstrated prostate specific antigen in the
      glands. It was diagnosed as cystosarcoma phyllodes tumor of prostate. This is
      extremely uncommon tumor similar in histology to that of breast and it's clinical
      course varies with the grade. The patient was without recurrence one year after
      surgery.

PMID- 15472413
TI  - Retro-peritoneal plasmacytoma: a case report and review of literature.
AB  - Solitary Extramedullary Plasmacytoma (EMP) is an uncommon neoplasm. When
      diagnosed, head and neck region is its most likely location. Rarely, it may occur
      in the retro-peritoneum. We report a 44 year old man with solitary extramedullary
      plasmacytoma in the retro peritoneum (RPEMP). The patient did not show response
      to three cycles of VAD chemotherapy. Thereafter Surgical excision of the mass was
      performed successfully. This is probably the first case report from Indian
      subcontinent.

PMID- 15472414
TI  - Diffuse large B-cell lymphoma arising from a multicentric mixed variant of
      Castleman's disease.
AB  - This case report describes a patient with multicentric mixed type Castleman's
      disease and concomitant non-Hodgkin's lymphoma of diffuse large B cell type in
      the neck. Multicentric CD is a systemic illness with disseminated
      lymphadenopathy; its aggressive and usually fatal course is associated with
      infectious complications and risk for malignant tumors, such as lymphoma or
      Kaposi sarcoma.

PMID- 15472415
TI  - Epithelial-myoepithelial carcinoma of the base of tongue: pathology and
      management.
AB  - Epithelial-myoepithelial carcinoma is a rare tumor which makes up about 0.2% of
      epithelial neoplasms of the salivary glands; parotid gland being the most common
      primary site of origin. The tumor may also very rarely originate in minor
      salivary glands of the base of the tongue. Due to rarity of its occurrence,
      histogenesis and clear cut therapeutic guidelines are not defined. The present
      report describes the case of a 48 year old male who was diagnosed to have a
      tubular variant of epithelial-myoepithelial carcinoma of the base of tongue,
      Stage T3 N0 M0 (Stage group III). The patient was treated with neoadjuvant
      chemotherapy followed by radical radiotherapy (Rt) and is alive with no evidence
      of disease 14 months following end of treatment.

PMID- 15472416
TI  - Mitochondrial neurological diseases: a clinician's perspective.

PMID- 15472417
TI  - Memantine: pharmacological properties and clinical uses.
AB  - Memantine is a relatively new drug specially developed for use in moderate-to
      severe dementia. It is an uncompetitive N-methyl-D-aspartate receptor antagonist
      and reduces glutamatergic excitotoxicity. Though Alzheimer's disease (AD) is the
      commonest cause of dementia in the world, there is no "cure" available for the
      same. Cholinesterase inhibitors such as donepezil and rivastigmine have been
      shown to provide symptomatic relief in patients with AD but have no effect on
      disease progression or survival. Moreover, they are not helpful in more severe
      stages of dementia. Memantine has been shown to cause modest improvement in
      clinical symptoms in severe stages of AD and may retard the disease progression.
      Moreover, it has been shown to be useful in various forms of dementia including
      AD, vascular dementia and Wernicke-Korsakoff psychosis. It is also the first drug
      to cause complete disappearance of pendular nystagmus due to multiple sclerosis.
      The current review focuses on the pharmacological properties of memantine and
      examines the recent evidence in favor of memantine.

PMID- 15472418
TI  - Vitamin B12 and folate depletion in cognition: a review.
AB  - In cross-sectional studies, low levels of folate and B12 have been shown to be
      associated with cognitive decline and dementia Evidence for the putative role of
      folate, vitamin B12 in neurocognitive and other neurological functions comes from
      reported cases of severe vitamin deficiencies, particularly pernicious anemia,
      and homozygous defects in genes that encode for enzymes of one-carbon metabolism.
      The neurological alterations seen in these cases allow for a biological role of
      vitamins in neurophysiology. Results are quite controversial and there is an open
      debate in literature, considering that the potential and differential role of
      folate and B12 vitamin in memory acquisition and cognitive development is not
      completely understood or accepted. What is not clear is the fact that vitamin B12
      and folate deficiency deteriorate a pre-existing not overt pathological situation
      or can be dangerous even in normal subjects. Even more intriguing is the
      interaction between B12 and folate, and their role in developing
      hyperhomocysteinemia. The approach to the rehabilitation of the deficiency with
      adequate vitamin supplementation is very confusing. Some authors suggest it, even
      in chronic situations, others deny any possible role. Starting from these quite
      confusing perspectives, the aim of this review is to report and categorize the
      data obtained from the literature. Despite the plausible biochemical mechanism,
      further studies, based on clinical, neuropsychological, laboratory and (lastly)
      pathological features will be necessary to better understand this fascinating
      biochemical riddle.

PMID- 15472419
TI  - Surgical approach to C1-C2 nerve sheath tumors.
AB  - BACKGROUND: C1 and C2 nerve sheath tumors (NST) are unique in presentation,
      relationship to neighbouring structures and surgical approaches when compared to
      their counterparts in other regions of the spine. AIM: The strategies involved in
      the surgery for C1-C2 NST are discussed SETTING AND DESIGN: Retrospective study.
      METHODS: 21 patients with C1 (n=6) and C2 (n=15) NST were operated based on their
      position with respect to the cord i.e. anterior (4), anterolateral (10),
      posterolateral (5), and posterior (2). The tumors had extra- and intradural
      components in 20 patients; while in one, the tumor was purely intradural. The
      operative approaches included the extreme lateral transcondylar approach (3);
      laminectomy with partial facetectomy (5); laminectomy (11); and, suboccipital
      craniectomy and laminectomy (2). RESULTS: Total excision was performed in 13
      patients; while in 7, a partial extraspinal component, and in 1, a small
      intradural component were left, in situ. Thirteen patients showed improvement by
      one or more grades in the Harsh myelopathy score; 2 patients with normal power
      had significant decrease in spasticity; while 5 maintained their grade. One poor
      grade patient succumbed to septicemia. CONCLUSIONS: C1-C2 NST may have exuberant
      growth due to the capacious spinal canal and the absence of a "true"
      intervertebral foramen at this level. Surgical approaches are determined by its
      relationship to the cord. A "T incision" on the dura, the partial drilling of the
      facets, sectioning of the denticulate ligament, rotating the operating table 15
      to 30 degrees, and at times sectioning the posterior nerve roots are all useful
      adjuncts for facilitating access.

PMID- 15472420
TI  - The treatment of complex dural arteriovenous fistulae through cranial base
      techniques.
AB  - INTRODUCTION: The endovascular modality of treatment is the preferred treatment
      modality for DAVF. In some circumstances, successful obliteration may not be
      possible by endovascular means, and such cases may require a direct surgical
      treatment. The authors report on their experience with the use of cranial base
      approaches in the treatment of deep and complex DAVF. MATERIALS AND METHODS: Nine
      patients were treated between 1992 and 2003. There were six females and three
      males. Four patients presented with intracerebral hemorrhage, two with
      progressive myelopathy, two with tinnitus, and one with incapacitating chronic
      seizures. Four DAVF were tentorial, two transverse sigmoid, one craniocervical,
      one straight sinus, and one sphenoparietal. Endovascular embolization was
      attempted and unsuccessful in four cases, and was successful only as an adjunct
      to surgery in four others. All patients required the use of cranial base
      approaches to disconnect the fistula or resect the nidus. RESULTS: Complete
      obliteration of the fistula was possible in all cases. Six-month follow-up
      results were obtained on seven patients where there was no evidence of
      recurrence. One postoperative temporal-lobe hematoma required surgical
      evacuation. One patient died two years postoperatively from an unrelated cause.
      CONCLUSION: This retrospective study demonstrates that complex DAVF can be
      successfully treated with the assistance of cranial base techniques.

PMID- 15472421
TI  - T2-weighted MRI in Parkinson's disease; substantia nigra pars compacta
      hypointensity correlates with the clinical scores.
AB  - BACKGROUND: Iron accumulation in substantia nigra pars compacta (SNpc) and
      related intensity and volumetric changes in patients with idiopathic Parkinson's
      disease (PD) has been reported previously. There are only a few studies
      evaluating the relation between neuroradiological findings and clinical scores,
      with contradictory results. AIMS: In this study we aimed to measure the iron-rich
      brain areas of PD patients and healthy subjects with T2-weighted magnetic
      resonance imaging (MRI) and to evaluate the relation between the clinical scores
      of PD patients and these imaging results. METHODS AND MATERIALS: T2-weighted MRI
      findings were studied in 20 patients with PD and 16 healthy controls. The width
      of SNpc, putamen volume, and the intensity of the basal ganglia were measured.
      Unified Parkinson's Disease Rating Scale (UPDRS) was used for evaluating the
      clinical status. STATISTICAL ANALYSES: Mann Whitney U test for group comparisons,
      Wilcoxon sign rank test for comparisons within the patient group, and Spearman's
      rank correlation coefficient for analyses of correlations were used. RESULTS:
      Mean SNpc and dentate nucleus intensities were lower in PD patients than healthy
      subjects. Mean SNpc width and putamen volumes were lower in patients. Decrease in
      the intensity of mean SNpc correlated with high UPDRS and rigidity scores.
      CONCLUSION: The results of our study reflect the increase in iron accumulation
      and oxidative stress in the SNpc in Parkinson's disease. The decrease in the
      intensity of SNpc correlates with poor clinical scores.

PMID- 15472422
TI  - Craniovertebral realignment for basilar invagination and atlantoaxial dislocation
      secondary to rheumatoid arthritis.
AB  - OBJECTIVE: We present our experience of treating nine consecutive cases of
      rheumatoid arthritis involving the craniovertebral junction by atlantoaxial joint
      manipulation and attempts towards restoration of craniovertebral region
      alignments. MATERIAL AND RESULTS: Between November 2001 and March 2004, nine
      cases of rheumatoid arthritis involving the craniovertebral junction were treated
      in our department of neurosurgery. Six patients had basilar invagination and
      'fixed' atlantoaxial dislocation and three patients had a retroodontoid process
      pannus and mobile and incompletely reducible atlantoaxial dislocation. The
      patients ranged from 24 to 74 years in age. Six patients were males and three
      were females. Neck pain and spastic quadriparesis were the most prominent
      symptoms. Surgery involved attempts to reduce the atlantoaxial dislocation and
      basilar invagination by manual distraction of the facets of the atlas and axis.
      Reduction of the atlantoaxial dislocation and of basilar invagination and
      stabilization of the region was achieved by placement of bone graft and metal
      spacers within the joint and direct inter-articular plate and screw method of
      atlantoaxial fixation. Following surgery all the patients showed symptomatic
      improvement and restoration of craniovertebral alignments. Follow-up ranged from
      four to 48 months (average 28 months). CONCLUSION: Manipulation of the
      atlantoaxial joints and restoring the anatomical craniovertebral alignments in
      selected cases of rheumatoid arthritis involving the craniovertebral junction
      leads to remarkable and sustained clinical recovery.

PMID- 15472423
TI  - Problems associated with the apnea test in the diagnosis of brain death.
AB  - BACKGROUND: Brain death is the absence of all cortical functions, including the
      brainstem. The apnea test (AT) is a necessary requisite to complete this
      diagnosis. Anecdotal reports describing hypotension and acidosis due to apnea
      test have been reported. However, there are few studies that evaluate
      complications or difficulties related to this procedure. OBJECTIVE: To analyze
      medical problems associated with the apnea test. METHODS AND PATIENTS: We
      analyzed clinical features, potential risk conditions, and problems in 129 brain
      dead patients during the apnea test. The diagnosis of brain death was made
      according to the American Academy of Neurology recommendations. RESULTS: Clinical
      problems during the apnea test were detected in more than two thirds of patients,
      including: arterial hypotension (12%), acidosis (68%), and hypoxemia (23%). Four
      patients developed major complications, including: pneumothorax, cardiac arrest,
      bradycardia, atrial fibrillation and myocardial infarction. CONCLUSION: The apnea
      test is not an innocuous procedure. Complications during the AT are more common
      than reported and limit organ procurement for transplantation. Guidelines for
      performing the AT should be followed in order to avoid clinical complications.

PMID- 15472424
TI  - Spectrum of intracranial subdural empyemas in a series of 45 patients: current
      surgical options and outcome.
AB  - BACKGROUND: The subject of subdural empyema (SDE) is reviewed on the basis of
      experience with 45 cases. METHODS: Records of 45 patients with SDE were analyzed.
      There were 35 males and 10 females in the series. The majority of the patients
      were either infants (22.2%) or in their second and third decade of life (37.8%).
      For supratentorial SDE, craniotomy was done in 5 cases (11.1%). In six cases
      (13.3%) two burr-holes and in the rest of the cases multiple burrholes were done
      to evacuate the empyema. Craniectomy was done in three cases (6.7%), of which two
      had posterior fossa SDE. All patients received appropriate preoperative and
      postoperative broad-spectrum antibiotics. RESULTS: There was good recovery in 35
      (77.8%) patients, six patients (13.3%) had moderate disability, two patients
      (4.4%) had severe disability, and two (4.4%) died. Three patients who developed
      recollection at operation site required evacuation of residual SDE. Median follow
      up was 3(1/2) years (range 4 months to 3(1/2) years). CONCLUSION: Emergent
      evacuation of SDE using multiple burr-holes and irrigation of the subdural cavity
      with saline for 24 hours results in a satisfactory outcome in cases with SDE.

PMID- 15472425
TI  - The effect of elbow position on biceps tendon reflex.
AB  - BACKGROUND: Testing of tendon (T) reflex is the basic method used in the
      diagnostic procedure of clinical neurology. Measurement of T reflexes precisely
      can be a valuable adjunct to clinical examination. Quantification of T reflexes
      may provide more accurate results. AIMS: To analyze the effect of elbow position
      on biceps T reflex. SETTINGS AND DESIGN: A self-controlled clinical trial of
      biceps T reflex testing at the Electrophysiology Unit of the Department of
      Physical Medicine and Rehabilitation. METHODS AND MATERIALS: Biceps T reflex was
      obtained utilizing a hand-held electronic reflex hammer in 50 extremities of 25
      healthy volunteers and the effect of elbow position (at 90 degrees , 120 degrees
      and 150 degrees ) on reflex response was evaluated. STATISTICAL ANALYSIS:
      Repeated-measures analysis of variance by the General Linear Model and Pearson
      correlation test procedures. RESULTS: Onset latency was significantly shorter at
      120 degrees of elbow position. The maximum amplitude value of biceps T reflex was
      obtained at 90 degrees of elbow position. Onset latency of the reflex correlated
      significantly with the height and arm length but not with age. CONCLUSIONS: The
      electrophysiological measurement of T reflexes is an easy and useful method in
      the quantification of reflexes, supplying more objective data. However, when
      performing T reflex studies, the position of the extremity should be taken into
      consideration to achieve more reliable results.

PMID- 15472426
TI  - Diagnosis of mitochondrial diseases: clinical and histological study of sixty
      patients with ragged red fibers.
AB  - BACKGROUND: Mitochondrial diseases are caused by mutations in mitochondrial or
      nuclear genes, or both and most patients do not present with easily recognizable
      disorders. The characteristic morphologic change in muscle biopsy, ragged-red
      fibers (RRFs) provides an important clue to the diagnosis. MATERIALS AND METHODS:
      Demographic data, presenting symptoms, neurological features, and investigative
      findings in 60 patients with ragged-red fibers (RRFs) on muscle biopsy, seen
      between January 1990 and December 2002, were analyzed. The authors applied the
      modified respiratory chain (RC) diagnostic criteria retrospectively to determine
      the number of cases fulfilling the diagnostic criteria of mitochondrial disease.
      RESULTS: The most common clinical syndrome associated with RRFs on muscle biopsy
      was progressive external ophthalmoplegia (PEO) with or without other signs, in 38
      (63%) patients. Twenty-six patients (43%) had only external ophthalmoplegia, 5
      (8%) patients presented with encephalomyopathy. Specific syndromes were the
      presenting feature in 8 (13%), Kearns-Sayre syndrome (KSS) in 4 and myoclonus
      epilepsy with ragged-red fibers (MERRF) in 4. Myopathy was the presenting feature
      in 5 (8%) and 4 presented with infantile myopathy. Of the 60 patients, 18 (30%)
      had proximal muscle weakness. Two patients with KSS and one patient with myopathy
      had complete heart block necessitating pace making. When the modified RC
      diagnostic criteria were applied, only 26 (43%) patients had one other major
      criterion in addition to RRFs for the diagnosis of mitochondrial diseases. The
      remaining 34 (57%) patients with RRFs on muscle biopsy had only some clinical
      features suggestive of RC disorder but did not fulfill the clinical criteria (of
      the modified diagnostic criteria) for the diagnosis of mitochondrial diseases.
      CONCLUSION: In patients with clinical features suggestive of RC disorder,
      demonstration of RRFs on muscle biopsy helps in confirming the diagnosis of
      mitochondrial disease in only a subgroup of patients.

PMID- 15472427
TI  - Demonstration of IgG antibodies to 30 Kd protein antigen in CSF for diagnosis of
      tuberculous meningitis by antibody-capturing ELISA.
AB  - OBJECTIVE: A simple and rapid immunological assay method has been developed to
      demonstrate the presence of IgG antibodies to 30Kd protein antigen (30Kdpa) and
      culture filtrate protein (CFP) in the CSF of patients with Tuberculous meningitis
      (TBM). METHOD: Antibody capturing Enzyme Linked Immunosorbent Assay (ELISA) was
      standardized with CFP antigen of MTB. The IgG antibodies were assayed in CSF
      sample from TBM and non-TBM patients against 30 Kdpa. RESULTS: The sensitivity
      and specificity of IgG antibodies for the diagnosis of suspected patients of TBM
      using 30 Kdpa was 80% and 91% respectively and the corresponding figures for CFP
      were 85% and 94% respectively. The sensitivity and specificity in two confirmed
      cases of TBM was 100%. CONCLUSION: The presence of this 30Kdpa in the CSF of
      suspected cases of TBM consistently would indicate that the selected protein band
      carries the candidate protein marker antigen, which is specific to M.
      tuberculosis and could be considered as a diagnostic marker for TBM.

PMID- 15472428
TI  - Becker's variant of myotonia congenita in two siblings--a clinico-genetic study.
AB  - We report a family of a brother and sister of myotonia congenita, conforming to
      autosomal recessive transmission (Becker's variety). To the best of our
      knowledge, no account of a family of autosomal recessive myotonia (Becker's
      disease), has earlier been reported from India.

PMID- 15472429
TI  - Metastatic lesions involving the sella: report of three cases and review of the
      literature.
AB  - Metastatic cancer must be considered as a possibility for intrasellar masses.
      Newer treatment modalities, such as gamma knife radiosurgery needs to be explored
      for these lesions. Three cases of intrasellar metastatic lesions were
      retrospectively reviewed. Presenting complaints, radiographic studies, operative
      procedure, and histopathological confirmation were recorded for each patient. All
      had an unknown primary malignancy prior to the presentation with the intrasellar
      lesion detected by magnetic resonance imaging (MRI). Presenting symptoms were
      diplopia with extraocular movement deficits in all patients. Transsphenoidal
      resection or biopsy was performed. Histopathological analysis revealed small cell
      carcinoma in two patients and plasmacytoma in one. All patients received
      postoperative radiation and/or chemotherapy. Survival following initial
      presentation was 2 months and 6 months for two of the patients; the third patient
      is alive at 2-month follow-up.

PMID- 15472430
TI  - Kluver-Bucy syndrome -- an experience with six cases.
AB  - The Kluver-Bucy syndrome (KBS) is a neurobehavioral syndrome and can be seen in
      association with a variety of neurological disorders. Case records of 6 patients
      with KBS seen during a period of 5 years in a university hospital were reviewed.
      During the study period 6 patients with KBS, aged between 4 and 14 years, were
      seen. Hyperorality, hypersexuality, and abnormal behavior were the most common
      manifestations. Of the 6 patients, 5 had recurrent unprovoked seizures. The
      associated neurological disorders included anoxia-ischemic encephalopthy (2),
      herpes simplex encephalitis (1), neurocysticercosis (NCC) (1), traumatic brain
      injury with gliosis (1 case) and tuberculous meningitis (1 case). Prognosis was
      poor in all the patients except in the patient with NCC.

PMID- 15472432
TI  - Glioblastoma multiforme in a child with acute lymphoblastic leukemia: case report
      and review of literature.
AB  - An 11-year-old boy with acute lymphoblastic leukemia had received prophylactic
      cranial irradiation (1800 cGy /10 fractions) and intrathecal methotrexate. Five
      years later, he developed a glioblastoma multiforme in the right frontal region
      while the leukemia was in remission. It is possible that the glioma may have been
      induced by radiation and /or chemotherapy.

PMID- 15472431
TI  - Childhood ataxia with cerebral hypomyelination (CACH) syndrome: a study of three
      siblings.
AB  - We report a family of three siblings with Childhood Ataxia with Cerebral
      Hypomyelination. All the siblings presented with early onset cerebellar ataxia
      beginning around five years of age with mild mental retardation. MRI showed
      diffuse white matter signal changes in all three patients with cerebellar atrophy
      while the spectroscopy was abnormal only in the eldest who was the most severely
      affected. The cases are reported for their rarity as well as for an opportunity
      of observing this uncommon disease in its stages of evolution in three siblings.

PMID- 15472433
TI  - Transitory alexia without agraphia: a disconnection syndrome due to
      neurocysticercosis.
AB  - We describe a 65-year-old male who presented with acute onset inability to read,
      without any difficulty in writing. A clinical diagnosis of alexia without
      agraphia was made and the patient was subjected to routine investigations
      including contrast MRI. MRI showed a ring-enhancing lesion in left occipital
      area, suggestive of neurocysticercosis supported by quantitative enzyme-linked
      immunosorbant assay from purified cell fraction of taenia solium cysticerci (PCF
      ELISA). Patient was treated with albendazole and prednisolone for one week. The
      clinical manifestation as well as the radiological finding resolved after
      treatment.

PMID- 15472434
TI  - Intradiploic meningioma of the orbit: a case report.
AB  - We report a case of a 12-year-old male child who presented with a gradual onset
      exopthalmos involving the left eye. The plain radiographs of the skull showed
      hyperostosis of the left orbital roof. The computerized tomography (CT) scan
      revealed an intradiploic orbital roof tumor with expansion of both the tables of
      the orbital roof. The tumor was completely excised by an extradural route using a
      basal frontal craniotomy. The histopathological diagnosis of the tumor was a
      psammomatous meningioma. A split calvarial frontal bone graft was used to
      reconstruct the orbital roof. The pathogenesis, radiological features and
      surgical technique involved in the management of intradiploic orbital roof
      meningioma are discussed and the relevant literature is reviewed.

PMID- 15472435
TI  - Carcinomatous meningitis mimicking Creutzfeldt-Jakob disease.
AB  - We report a case of carcinomatous meningitis diagnosed at autopsy that was
      clinically diagnosed as a case of Creutzfeldt-Jakob disease (CJD) because of
      rapidly evolving dementia. Pathological study revealed diffusely spreading
      carcinomatous meningitis, infiltrating into cortex along Virchow Robin space.
      Immunostaining for Prion protein was negative. Despite advances in clinical
      diagnosis, tissue diagnosis remains a pre-requisite for confirmation of CJD.

PMID- 15472436
TI  - Desmoplastic infantile ganglioglioma -- a case report.
AB  - Desmoplastic infantile ganglioglioma is a very rare supratentorial tumor
      occurring in the first two years of life. A five-month-old female infant
      presented with recurrent seizures, large head and loss of acquired milestones.
      Computerized Tomographic Scan of brain showed a large subarachnoid cyst with a
      solid intensely contrast enhancing tumor in the right temporoparietal region with
      severe degree of mass effect. Craniotomy and total excision of the tumor followed
      subsequently by subduro-peritoneal shunt for the extracerebral fluid collection
      was done. The child made good recovery. Histopathology revealed features of
      desmoplastic infantile ganglioglioma, viz., marked desmoplastic component with
      glial and neuronal elements. Immunohistochemistry showed positive staining for
      glial fibrillary acidic protein (GFAP) with areas of synaptophysin and
      chromogranin positivity. Desmoplastic infantile ganglioglioma is a rare tumor of
      infancy, which has excellent prognosis after total excision. No adjuvant therapy
      is required. This is the first Indian report of desmoplastic infantile
      ganglioglioma out of less than fifty cases reported worldwide.

PMID- 15472437
TI  - Total external ophthalmoplegia induced by phenytoin: a case report and review of
      literature.
AB  - A 28-year-old male developed total external ophthalmoplegia following oral
      administration of phenytoin. The case is reported and its significance is
      discussed.

PMID- 15472438
TI  - Calvarial malignant fibrous histiocytoma.
AB  - Primary malignant fibrous histiocytoma (MFH) of the central nervous system (CNS)
      is uncommon. We report cases of two young patients of MFH arising from the
      cranial meninges and involving the adjacent skull and scalp. There was
      infiltration of the brain in one case. Both the lesions were excised and primary
      scalp repair was performed.

PMID- 15472439
TI  - An intramedullary tumor presenting with hyperhidrosis.
AB  - A case of a cervical intramedullary tumor is reported whose presentation was with
      disabling hyperhidrosis. The symptom resolved after surgical debulking of the
      tumor. Hyperhidrosis as a presenting manifestation of an intramedullary tumor has
      not been reported earlier.

PMID- 15472440
TI  - Nimodipine in severe head injury.

PMID- 15472441
TI  - Usefulness of head up tilt test in the diagnosis of neurocardiogenic syncope.

PMID- 15472442
TI  - Ventriculo-peritoneal shunt infection by mycobacterium fortuitum in an adult.

PMID- 15472443
TI  - Role of nimodipine in severe diffuse head injury.

PMID- 15472444
TI  - Intravenous valproate in post-anoxic myoclonic status epilepticus: a report of
      ten patients.

PMID- 15472445
TI  - Middle cranial fossa schwannoma of the facial nerve.

PMID- 15472446
TI  - Giant cell arteritis as a cause of jaw claudication.

PMID- 15472447
TI  - Non-equivalence of bioavailability between generic and branded form of sodium
      valproate.

PMID- 15472448
TI  - An artificial neural network to detect EEG seizures.

PMID- 15472449
TI  - Delayed tension pneumocephalus: a rare complication of shunt surgery.

PMID- 15472450
TI  - Thoracic neurenteric cyst in a 60 year old male.

PMID- 15472451
TI  - Recurrent oculomotor nerve palsy: a rare presentation of neurocysticercosis.

PMID- 15472452
TI  - Thecoperitoneal shunt in case of symptomatic anterior sacral meningocele.

PMID- 15472453
TI  - Blinking of the eye on voluntary movement on the side of paralysis in a case of
      cerebrovascular accident.

PMID- 15472454
TI  - Klinefelter's syndrome with myopathy--a case report.

PMID- 15472455
TI  - Lower end of ventriculoperitoneal shunt embedding in liver parenchyma.

PMID- 15472456
TI  - Moving bullet syndrome.

PMID- 15472458
TI  - A 12-week structured education and exercise program improved climacteric symptoms
      in middle-aged women.
AB  - In the present study, 40- to 60-year-old women with climacteric symptoms were
      placed on a 12-week structured education and exercise program to ascertain the
      effects of this program on climacteric symptoms, quality of life (QOL), and
      attitude towards exercise. A total of 35 women served as subjects. Twenty women
      were enrolled in an educational and exercise program that involved learning about
      menopause and participating in physical activity at least three times a week
      (Group E). For comparison, the other 15 women did not participate in this program
      and were instructed to refrain from exercising during study period (Group C). The
      effects of the 12-week interventional program on climacteric symptoms, QOL, and
      attitude towards exercise were thereby investigated. The program demonstrated
      significant effects on climacteric symptoms in terms of Kupperman index and
      psychosomatic symptoms, especially paresthesia and nervousness. In other words,
      climacteric symptoms improved significantly in Group E. Furthermore, scores for
      QOL and attitude towards exercise improved in Group E after the 12-week program;
      however, these trends did not reach statistical significance. Hence, the 12-week
      structured education and exercise program was shown to be effective in
      alleviating climacteric symptoms.

PMID- 15472459
TI  - The effect of safety hat on thermal responses and working efficiency under a high
      temperature environment.
AB  - The purpose of this study is to examine the effect of a safety hat on thermal
      responses and work efficiency under a high temperature environment. Five healthy
      male subjects participated in the repeated 'Rest' and 'Exercise' periods in order
      to compare a safety hat without holes (annoted as 'without hole') and a safety
      hat with holes (annoted as 'with hole') in a climatic chamber of 30 degrees C,
      50%RH. The main findings are as follows: (a) the core temperature (tympanic
      temperature) and heart rate showed significantly lower levels in the subjects who
      are under the 'with hole' condition than those who are under the 'without hole'
      condition; (b) the forehead skin temperature was significantly higher in the
      subjects who are under the 'without hole' condition than those who ar uder the
      'with hole' condition; (c) blood pressure was significantly lower in the 'with
      hole' condition; and (d) sweat rate which was measured by weight loss before and
      after the experiment was higher in the 'without hole' condition; and (e) work
      ability which was measured by a grip strength dynamometer was higher in the 'with
      hole' condition. Making a hole in the safety hat, designed for proper ventilation
      and hygiene, is practical in letting out heat and decreasing the physiological
      burden under a hot working environment. The safety hat with holes is useful in
      maintaining the homeostasis of the body temperature by releasing body heat
      efficiently and it is meaningful to keep the working efficiency.

PMID- 15472460
TI  - Secular trends of sizes at birth in Japanese healthy infants born between 1962
      and 1988.
AB  - Body sizes at birth are important clinical indicators widely used for evaluation
      of prenatal growth. Japan had significant socioeconomic improvement around the
      1960s, and these environmental changes may influence physiologically prenatal
      growth. Furthermore, in Japan, measurements of size at birth for birth
      certificates are weight and height. Thus, we can refer to annual data on weight
      and height, but not on head and chest circumference at birth. In this study we
      measured the weight, height, and head and chest circumference at birth among
      6,563 Japanese singleton healthy infants, annually in 1962 and 1988, and examined
      secular trends of these anthropometric measurements. The boys consistently
      exceeded the girls in all four variables. Birth weight and height increased
      significantly from the 1960s to '70s, but did not differ between the '70s and
      '80s in both boys and girls. Secular trends of head and chest circumference were
      different from them. In both boys and girls, head and chest circumference
      increased significantly from the '60s to the '70s, but decreased significantly
      from the '70s to the '80s. No difference of head circumference during the '60s
      and '80s was found, but the difference of chest circumference was found. Size at
      birth was likely to increase from the '60s to '70s in Japan. These findings
      suggest that the environmental changes such as socioeconomic improvements
      influence the prenatal growth.

PMID- 15472461
TI  - Effects of habitual smoking on cardiorespiratory responses to sub-maximal
      exercise.
AB  - The effects of habitual cigarette smoking on cardiorespiratory responses to sub
      maximal and maximal work were evaluated in nine adult nonsmokers and nine smokers
      with a mean age of 33 yr. A maximal treadmill test was followed by three tests at
      45, 60 and 75% of each subject's VO(2)max. Compared to nonsmokers, the habitual
      smokers had a non-significantly lower VO(2)max in L/min and per lean body mass (9
      and 6%, respectively), but had higher %fat (p<0.01), resulting in a significantly
      lower VO(2)max per kg body wt (13%, p<0.03). Maximal exercise ventilation (V(E))
      was 16% lower in smokers. During sub-maximal work at equivalent exercise stress
      levels in the two groups, the V(E)/VO(2) ratio was higher in smokers by an
      average of 11% because VO(2) was lower and the respiratory exchange ratio values
      were significantly elevated in smokers at 75% of VO(2)max. Blood lactate
      concentrations in smokers were higher as workloads increased and O(2) pulse
      (VO(2)/HR) was significantly lower throughout, indicating reduced O(2)
      extraction, probably due to carbon monoxide. The resting HR was significantly
      higher in smokers and the HR recovery following all three submaximal exercises
      was significantly slower in smokers. These results show that detrimental
      cardiorespiratory effects of chronic cigarette smoking in apparently healthy
      individuals are evident at moderate exercise levels as reduced gas exchange
      efficiency in lungs and muscles.

PMID- 15472462
TI  - Testicular compensatory hypertrophy related to hemicastration in prepubertal
      dogs.
AB  - Several studies have reported that the plasma testosterone (T) level and semen
      volume are compensated after hemicastration (HEC) in adult dogs, but that the
      sperm count is not. Nevertheless, the effects of HEC in prepubertal dogs have not
      been reported. In this study, HEC was performed at 16 weeks of age in 8 male
      beagles, and the function of the residual testis was investigated until 48 weeks
      of age. The testis volume was consistently higher in the HEC group than the
      control (CON) group. After 40 weeks of age, compensatory hypertrophy was
      observed, with a mean testis volume of 125% of that in the CON group (p<0.05).
      Furthermore, the semen volume and plasma testosterone (T) level were similar to
      those in the CON group, suggesting functional compensation, but the sperm count
      was not compensated. These results showed that the testis volume, semen volume,
      and plasma T level were compensated after HEC in prepubertal dogs, but the
      spermatogenic function was not.

PMID- 15472463
TI  - Protease-induced hyperactivation of canine spermatozoa associated with
      disappearance of lectin-binding glycoproteins on their surface.
AB  - The relationship between the disappearance of glycoproteins from the surface of
      canine sperm and sperm capacitation was investigated in vitro. The protease (PR)
      concentration in flush fluids of the uterine horns and oviducts removed from 6
      estrous, 5 diestrous, and 5 anestrous bitches was measured with a protease assay
      kit. Ejaculated sperm collected from 10 dogs were incubated for 4 hr in Eagle's
      MEM supplemented with 1 or 5 microg/ml PR, or to which no PR had been added
      (control). The glycoproteins on the surface of the sperm were stained with 4
      different FITC-lectins (Con A, PHA-E, PNA, and WGA), and the percentages of
      hyperactivated (HA-) sperm and acrosome-reacted (AR-) sperm were evaluated. The
      mean PR concentration (5.95 microg/ml) in the flush fluid from the oviducts of
      the estrous bitches was significantly higher than in the fluid from their uterine
      horns (1.00 microg/ml; P<0.01). The PR concentrations of the flush fluids from
      the uterine horns and oviducts of both the diestrous and anestrous bitches were
      less than 0.05 microg/ml. Before incubation the acrosomal regions or entire heads
      of all sperm clearly stained with each FITC-lectin, but the percentages of sperm
      binding the 4 FITC-lectins decreased after incubation. The percentages of lectin
      binding sperm in the MEM containing 5 microg/ml PR were significantly lower than
      in the control MEM (P<0.05 and 0.01). The mean percentages of motile sperm and HA
      sperm after incubation in the MEM with PR were higher than in the control MEM,
      but there were no differences in the percentages of AR-sperm. The results
      indicate that HA-movement of sperm is induced by the disappearance of
      glycoproteins from the surface of canine sperm as a result of the action of PR in
      the oviductal fluid of estrous bitches.

PMID- 15472464
TI  - Further mapping and characterization of Naq1, a quantitative trait locus
      responsible for maternal inferior nurturing ability in RR mice.
AB  - Females of the inbred mouse RR strain have a limited ability to nurture their
      offspring, and frequently the young die during rearing. We previously identified
      a significant quantitative trait locus (QTL) responsible for the inferior
      nurturing ability on chromosome 5 (Naq1), on the basis of litter weight of six
      pups at days 7, 12, and 21 after parturition. Here, we carried out further
      mapping of Naq1 to define the confidence interval precisely. At the same time, we
      analyzed new quantitative trait variables, litter weight gain between days 7 and
      12 (WG1), and that between days 12 and 21 (WG2), to characterize further the
      physiology of inferior nurturing ability. Consequently, a peak LOD score for the
      Naq1 was identified on D5Mit218 (72 cM), which was located approximately 2 cM
      distal to our previous expectation, as a significant QTL for WG1 (LOD 5.5), but
      not for WG2 (LOD 0.9). Because the growth of pups depends purely on milk obtained
      from the dam up to day 12 after birth, it seems possible to assume that the
      inferior nurturing ability in RR mice is related to defects in maternal
      nutritional support (that is, lactation) rather than to defects in pup growth.
      Naq1 is a novel QTL as far as the QTL results of relevant female reproductive
      traits in cattle and pigs are concerned.

PMID- 15472465
TI  - Confirmation and characterization of murine body weight QTLs, Bwq1 and Bwq2,
      identified in C57BL/6J x KK-Ay/a F2-Ay/a mice.
AB  - Body weight quantitative trait loci (QTLs), Bwq1 and Bwq2, identified previously
      in C57BL/6J x KK-Ay/a F2-Ay/a mice, were further confirmed and characterized.
      Body weight measurement was done from 21 days after birth (Day 21) through Day
      100, at 10-day intervals. Bwq1 was statistically significant only on Days 40, 50,
      and 60, whereas Bwq2 was statistically significant on and after Day 40. When body
      weight gain (WG) between two successive weight measurements was evaluated, both
      Bwq1 and Bwq2 were statistically significant only for WG between Days 30 and 40.
      The results suggest that variations in body weight among F2-Ay/a individuals in
      later life have been determined by variations in WG during the period shortly
      after weaning. The results also suggest that Bwq1 is related to increased body
      weight in the KK strain, because the effect of Bwq1 on the body weight is
      observed not only in F2-Ay/a, but also in F2-a/a. On the other hand, it is
      suggested that Bwq2 is related to enhanced obesity caused by Ay mutation and
      therefore is a genetic modifier that specifically interacts with the Ay allele,
      because the effect of Bwq2 is only observed in F2-A y/a. There are two candidate
      genes, Pparg and Hrh1, which are located near the 95% confidence interval of
      Bwq2, and which are expressed in the adipose tissue; however, we could not find
      any nucleotide differences in both cDNAs between KK and C57BL/6J strains.

PMID- 15472466
TI  - Effects of various selective phosphodiesterase inhibitors on carbachol-induced
      contraction and cyclic nucleotide contents in guinea pig taenia coli.
AB  - Effects of various selective phosphodiesterase (PDE) inhibitors on muscle
      contractility and cyclic nucleotide contents in guinea pig taenia coli were
      investigated. Forskolin and sodium nitroprusside inhibited carbachol (CCh)
      induced contraction in a concentration-dependent manner. Various selective PDE
      inhibitors, vinpocetine (type 1), erythro -9-(2-hydroxy-3-nonyl)adenine (EHNA,
      type 2), milrinone (type 3), Ro20-1724(type 4) and zaprinast (type 5) inhibited
      CCh-induced contraction in a concentration-dependent manner, but the inhibition
      of milrinone was noticeably smaller than that of the other PDE inhibitors. The
      rank order of potency was zaprinast > vinpocetine > EHNA > Ro20-1724 > milrinone.
      In the presence of CCh (0.3 microM), vinpocetine and Ro20-1724 both increased
      cAMP content, but not cGMP. By contrast, EHNA and zaprinast both increased cGMP
      content, but not cAMP. Pretreatment with ODQ (30 microM), a soluble guanylyl
      cyclase inhibitor, decreased the inhibition of CCh-induced contraction by EHNA or
      zaprinast. Pretreatment with SQ22536 (100 microM), an adenylyl cyclase inhibitor,
      decreased the inhibition of CCh-induced contraction by vinpocetine or Ro20-1724.
      In conclusion, it was indicated that vinpocetine- or Ro20-1724-induced relaxation
      was correlated with cAMP but EHNA- or zaprinast- induced relaxation was
      correlated with cGMP.

PMID- 15472467
TI  - Generation of monoclonal antibodies to porcine interleukin 6 (PIL-6) using the
      recombinant PIL-6 expressed in Escherichia coli.
AB  - Porcine interleukin-6 (PIL-6) protein without signal peptide was expressed as a
      glutathione S-transferase (GST) fusion protein in Escherichia coli. The fusion
      protein was expressed in an insoluble fraction, however, it was solubilized by
      refolding procedure using urea. From the solubilized protein, the recombinant PIL
      6 (rPIL-6) was purified by a batch method using glutathione sepharose 4B and
      PreScission protease cleavage. By the B3B1 hybridoma cell proliferation assay,
      biological activity of the purified rPIL-6 was confirmed. Three monoclonal
      antibodies (MAbs) named 2B-1, 5A-8 and 4C-3 were generated by using the rPIL-6 as
      an immunogen. Immunoglobulin isotypes of the MAbs were IgG2a (4C-3) and IgG2b (2B
      1 and 5A-8). For the epitope analysis, additive enzyme-linked immunosorbent assay
      and immunoblot analysis using deletion mutants of PIL-6 were performed. These
      experiments revealed that the two MAbs (2B-1 and 5A-8) recognize an overlapped
      epitope and the other (4C-3) recognizes a distinct epitope, and all epitopes
      reside in the region of aa26-64 of PIL-6.

PMID- 15472468
TI  - Zinc uptake system (znuA locus) of Brucella abortus is essential for
      intracellular survival and virulence in mice.
AB  - Brucella spp. are facultative intracellular pathogens that have the ability to
      survive and multiply in professional and nonprofessional phagocytes, and cause
      abortion in domestic animals and undulant fever in humans. The mechanism and
      factors of virulence are not fully understood. High-affinity zinc uptake system
      protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and
      failed to replicate in HeLa cells and mouse bone marrow-derived macrophages.
      Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA
      gene restored the growth in zinc chelated medium and intracellular replication in
      HeLa cells and macrophages to a level comparable to that of wild-type strain.
      Bacterial internalization into HeLa cells and macrophages and co-localization
      with either late endosomes or lysosomes of znuA mutant were not different from
      those of wild-type strain. These results suggest that znuA does not contribute to
      intracellular trafficking of B. abortus, but contributes to utilization of zinc
      required for intracellular growth.

PMID- 15472469
TI  - Generation of multinucleated giant cells in vitro from bovine monocytes and
      macrophages.
AB  - The generation of multinucleated giant cells (MGC) from cells of the bovine
      monocyte-macrophage lineage was investigated. Freshly isolated monocytes were
      incubated with the conditioned medium (CM) of peripheral blood mononuclear cell
      cultures treated with Concanavalin A for 1-4 days (CM1 to CM4). Only CM1
      generated MGC despite similar concentrations of IFNgamma in all CMs.
      Nevertheless, MGC formation from monocytes was enhanced by adding either
      macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony
      stimulating factor (GM-CSF), MGC formations from macrophages were observed only
      when macrophages were cultured with GM-CSF plus CM. These results indicate that
      several mechanisms to generate MGC from bovine monocytes-macrophage lineage cells
      exist, and that GM-CSF is a major mediator of MGC formation in cattle.

PMID- 15472470
TI  - Relationship between growth hormone (GH) pulses in the peripheral circulation and
      GH-releasing hormone and somatostatin profiles in the cerebrospinal fluid of
      goats.
AB  - Growth hormone (GH) is secreted in a pulsatile manner, but the underlying
      mechanisms of GH pulse generation remain to be resolved. In the present study, we
      investigated the relationship between GH pulses in the peripheral circulation and
      GH-releasing hormone (GHRH) and somatostatin (SRIF) profiles in the cerebrospinal
      fluid (CSF) of male goats. The effects of an intracerebroventricular (icv)
      injection of neuropeptide Y (NPY), galanin and ghrelin were also analyzed. Blood
      and CSF samples were collected every 15 min for 8 hr from the jugular vein and
      third ventricle, respectively. GH pulsatility in the goat was found to consist of
      distinct large pulses of 5 hr periodicity and small pulses of 1 hr periodicity.
      GHRH and SRIF in the CSF fluctuated in a pulsatile manner with 1 hr periodicity,
      and most of the descending phase of SRIF pulses were associated with the
      initiation of GH pulses. Icv injections of NPY, galanin and ghrelin stimulated
      GHRH release without affecting SRIF release. In addition, NPY suppressed, and
      galanin and ghrelin induced large GH pulses, although ghrelin was much more
      effective than galanin. These results suggest that an hourly fall in SRIF is
      involved in generating intrinsic circhoral rhythm of GH pulsatility. The
      mechanisms underlying the generation of large GH pulses of 5 hr periodicity
      remain unknown, while direct action of NPY and/or ghrelin on the pituitary might
      be involved.

PMID- 15472471
TI  - Effect of PCB-126 on intracellular accumulation and transepithelial transport of
      vinblastine in LLC-PK1 and its transformant cells expressing human P
      glycoprotein.
AB  - The effects of 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB-126), which is the most
      toxic congener of coplanar polychlorinated biphenyls (Co-PCBs), on intracellular
      accumulation and transepithelial transport of vinblastine were examined in
      porcine kidney cells, LLC-PK1, and its transformant cells expressing human P
      glycoprotein (LLC-MDR1). The accumulation decreased less than one-tenth in LLC
      MDR1 compared to LLC-PK1. In both cells, the accumulation increased with the
      addition of PCB-126 and cyclosporine A (CYA), which are P-glycoprotein
      modulators, though the magnitudes were different in these two cell groups as well
      as for these two chemicals. Thus, PCB-126 might inhibit extrusion of vinblastine
      through the drug extrusion system as does CYA. In both the cells, there might be
      an endogenous drug extrusion system other than P-glycoprotein that was inhibited
      by CYA or PCB-126. The net basal-to-apical transepithelial transport of
      vinblastine increased 1.7-fold more in LLC-MDR1 than in LLC-PK1. By adding PCB
      126 on the apical side, the transport was greatly decreased by -76% in the
      monolayer of both cells. By adding PCB-126 and CYA on the basal side in LLC-MDR1
      monolayer, the transports increased -1.7-fold, so that PCB-126 might inhibit the
      extrusion of vinblastine on both the apical and basal sides. One of the causes to
      be considered for the adverse effects of Co-PCBs, in addition to the binding with
      an aryl hydrocarbon receptor, might be the modification of drug transport by its
      interaction with the drug transport system.

PMID- 15472472
TI  - Comparison of the acid-phosphatase staining and polymerase chain reaction for
      detection of Dirofilaria repens infection in dogs in Korea.
AB  - This study was performed to compare acid-phosphatase staining with polymerase
      chain reaction (PCR) analysis for the diagnosis of Dirofilaria repens infection.
      The infection of D. repens was confirmed in Korean reared German shepherd dogs.
      Knott's tests were carried out for the detection of microfilaria in 543 Korean
      reared German shepherd dogs (255 females and 288 males). Eighty four of the 543
      dogs (15.5%) showed microfilaria-positive reactions with the modified Knott's
      test, and the test-positive microfilariae were then examined by both acid
      phosphatase staining and PCR analysis. Six (7.1%) and 17 (20.2%) of the 84
      microfilaria-positive samples, by the Knott's tests were positive to D. repens by
      acid-phosphatase staining and in D. repens-specific PCR analysis, respectively.
      All samples found to be positive by the acid-phosphatase staining were also found
      to be positive by PCR analysis. Therefore, we conclude that PCR analysis (20.2%)
      is more valuable for the diagnosis of D. repens infection than acid-phosphatase
      staining (7.1%) (p<0.001).

PMID- 15472473
TI  - Reverse effects of tetraarsenic oxide on the angiogenesis induced by nerve growth
      factor in the rat cornea.
AB  - To compare the antiangiogenic effects of tetraarsenic oxide (As4O6) with those of
      diarsenic oxide (As2O3) in the rat cornea, rat cornea micropocket assay was
      conducted to induce angiogenesis by implantation of the pellet contained 1.0 ng
      of nerve growth factor (NGF). Ten of thirty eyes of Sprague-Dawley rats were
      randomly assigned to one of three groups, namely, control group (no medication),
      As2O3 group (50 mg/kg As2O3, PO, s.i.d.), and As4O6 group (50 mg/kg As4O6, PO,
      s.i.d.). After implantation, the number of new vessels, vessel length and clock
      hour of neovascularization were examined under the microscope from day 3 to day
      7. The area of neovascularization was calculated using a mathematical formula.
      Although new vessels in control and As2O3 groups were first noticed at day 3,
      whereas those of As4O6 group were first observed on day 5. The number, length,
      clock hour of neovascularization and areas of the vessels in As4O6 group showed
      more significant inhibition than those of control and As2O3 groups from day 5
      (P<0.05). However, there were no differences in all parameters between control
      group and As2O3 group during the entire study period. These results showed that
      As4O6 had antiangiogenic effects on the new vessels induced by NGF in the rat
      cornea.

PMID- 15472474
TI  - Effects of dopamine, dobutamine, amrinone and milrinone on regional blood flow in
      isoflurane anesthetized dogs.
AB  - The effects of cyclic AMP increasing cardiotonics (dopamine, dobutamine, amrinone
      and milrinone) on the blood flow in most organs were compared using colored
      microsphere technique in isoflurane-anesthetized dogs. Dopamine increased blood
      flow in ventricular myocardium. Furthermore dopamine induced the increase in
      blood flow in intestine and kidney at low to middle dose, but not at high dose.
      Dobutamine induced the highest increase in blood flow in ventricular myocardium
      and skeletal muscle among the drugs evaluated at middle and high doses. Amrinone
      and milrinone increased blood flow in ventricular myocardium almost same with
      catecholamines, and milrinone decreased vascular resistance moderately in most
      other organs. Milrinone might be more useful than catecholamines for improvement
      of congestive heart failure or peripheral circulatory failure accompanied with
      exceeded vasoconstriction.

PMID- 15472475
TI  - Evaluation of QT interval prolongation in dogs with heart failure.
AB  - Comparison of the QT interval and corrected QT interval values that were
      calculated by the methods of Bazett (QTc1) and Fridericia (QTc2) were made
      between dogs with or without cardiac diseases to determine the influence of the
      QT interval on canine heart failure. Upon comparison of the measured values on
      ECG between the cardiac disease and non-cardiac disease groups, it was observed
      that the heart rate(HR) was significantly higher in the cardiac disease group
      than in the non-cardiac disease group, although the QT interval was similar in
      the two groups. The QTc1 and QTc2 were significantly longer in the cardiac
      disease group than in the non-cardiac disease group. With the progression of the
      New York Heart Association Class, the HR tended to increase. The QTc1 and QTc2
      became significantly prolonged with the progression of heart failure.
      Nevertheless, because Bazett's correction formula is known to overcorrect when
      the HR is high, it was considered that the QTc1 was actually overcorrected by
      high HR with the progression of heart failure. The QTc2, on the other hand, was
      only slightly influenced by HR, suggesting that the prolongation was due to the
      progression of heart failure. These results suggest that the prolongation of QTc2
      in cardiac disease reflects the substantial prolongation of the QT interval
      without the influence of HR. It is suggested that the QTc2 could be a useful
      parameter for assessing the degree of heart failure in dogs with cardiac disease.

PMID- 15472476
TI  - Decreases in serum apolipoprotein C-III concentration in cows with ethionine
      induced fatty liver.
AB  - To monitor the serum concentration of apolipoprotein C-III (apoC-III), one of the
      functional apoproteins in lipid metabolism, in cows with ethionine-induced fatty
      liver, and to investigate the association of apoC-III with liver triglyceride
      (TG) content and serum biochemical variables, seven nonpregnant nonlactating
      Holstein cows (3 to 6 years old) were used. Five cows were treated with
      ethionine, an analogue of methionine, (days 0, 7 and 14). The remaining two
      controls received saline as the vehicle. Liver TG contents in the treated cows
      were increased markedly whenever administered, and significant increases were
      observed at days 14 (666.4%, 85.3 mg/g) and 21 (675.0%, 86.4 mg/g) compared with
      day 0. In controls, no significant changes in liver TG content and serum
      biochemical variables were observed during this experiment. The serum apoC-III
      concentration in the treated cows was decreased drastically after the first
      administration and fell to the lowest value at day 10 (76.2 microg/ml, 32% of day
      0). The apoC-III was significantly (p<0.05) correlated with non-esterified fatty
      acids (r= -0.526), gamma-glutamyl transpeptidase (r= -0.407), total bilirubin (r=
      -0.464), positively with apolipoprotein B-100 (apoB-100, r=0.601) and cholesterol
      ester (r=0.449). Although apoB-100 concentrations were also reduced by the
      administrations, the concentrations tended to recover smoothly toward the next
      administration. The distinct difference in change between apoC-III and apoB-100
      suggests that apoC-III may be regulated by other pathways, in addition to
      inhibiting the synthesis of apoproteins by ethionine.

PMID- 15472478
TI  - Development of spermatogenic function in the sex maturation process in male cats.
AB  - The spermatogenic function and plasma testosterone (T) level in the sex
      maturation process were investigated as to 180 mixed breed cats ranging from 4
      months to 2 years in age to be castrated. Testis/epididymis weights reached a
      peak at 10 and 8 to 9 months of age, respectively. In the testis, sperm appeared
      at 5 months of age. At 7 months of age, sperm were observed in 96.2% of the cats.
      In the tail of the epididymis, sperm appeared in 46.9% of the cats at 6 months of
      age and in all cats at 8 or more months of age. Furthermore, the mean plasma T
      level rapidly increased at 8 months of age, and reached a peak (2.64 +/- 0.68
      (SE) ng/ml) at 10 months of age. Three of 180 cats (1.67%) had unilateral
      cryptorchidism. These results suggest that the spermatogenic function in male
      cats becomes mature at 8 to 10 months of age.

PMID- 15472477
TI  - Alterations of activities of cytosolic phospholipase A2 and arachidonic acid
      metabolizing enzymes in di-(2-ethylhexyl)phthalate-induced testicular atrophy.
AB  - Di-(2-ethylhexyl) phthalate (DEHP), a peroxisome proliferator-activated receptor
      alpha (PPARalpha) ligand, alters the lipid composition of rat testis, yet the
      mechanism is unclear. In this study, we investigated the effect of DEHP on the
      synthesis and metabolism of arachidonic acid (AA), a precursor of eicosanoids, in
      the testis of prepubertal rats. DEHP (100 and 1,000 mg/kg, 5 days) administration
      caused a significant reduction in activity of cytosolic phospholipase A2 (cPLA2),
      the rate-limiting enzyme in the AA and eicosanoid synthesis pathways. DEHP
      increased the expression of 12-lipoxygenase (12-LOX) in rat testis, whereas
      cyclooxygenase-2 (COX-2) expression was not altered. Cytochrome P450 4A1
      (CYP4A1), a product of a PPARalpha-regulated gene, was markedly increased in the
      testis by DEHP administration. Taken together, DEHP suppresses cPLA2 activity and
      induces the AA metabolizing enzymes such as 12-LOX and CYP4A1, resulting in the
      reduction of AA level. These data suggest that altered AA metabolic cascades may
      be related to the decrease of testosterone concentration in DEHP-induced
      testicular atrophy.

PMID- 15472479
TI  - Breeding season in female cats acclimated under a natural photoperiod and
      interval until puberty.
AB  - The breeding season was investigated in 174 female cats that were acclimated
      under a natural photoperiod, and determined the interval between birth and
      initial estrus (puberty) was determined in 125 cats. Although the breeding season
      differed noticeably among individual animals, the mean was 180.4 +/- 3.0 (SE)
      days between the end of January and the end of July. The interval between birth
      and first estrus ranged from 181 to 560 days, with a mean of 345.0 +/- 0.9 days.
      With respect to month of birth, the mean interval was 343.0 +/- 9.5 days in cats
      born between March and June. Among cats that were born between July and October,
      the mean intervals were 242.0 +/- 6.3 days in cats that exhibited estrus the year
      after birth and 519.2 +/- 5.8 days in those that exhibited estrus 2 years after
      birth.

PMID- 15472480
TI  - Severe calcification of mucocutaneous and gastrointestinal tissues induced by
      high dose administration of vitamin D in a puppy.
AB  - A three-month-old male Bull Terrier was referred to the Animal Medical Centre,
      Nihon University with chief complaints of subacute emesis and lethargy. Severe
      leukocytosis, high CRP, hypercalcemia and hypochloremia were detected. Moreover,
      severe calcification of gingival mucosa and abdominal skin, and abnormalities of
      the skeletal system were discerned. Abdominal X-ray and endoscopic examination
      revealed ulcer and hemorrhage on the mucosal membrane of the stomach. This might
      have been due to injections of high dose vitamin D at 3 and 2 weeks ago by
      another practioner, according to the detailed history of medication. After two
      months, a gastrointestinal and skin disorder disappeared, although calcification
      of the stomach membranes remained and abnormality of the skeletal system had
      worsened. Therefore, vitamin D should be carefully administrated to a puppy.

PMID- 15472481
TI  - Bone cement treatment for aneurysmal bone cyst in a dog.
AB  - An eighteen month old female Doberman pinscher dog was referred to teaching
      hospital of Adnan Menderes University, Faculty of Veterinary Medicine with the
      complaint of right forelimb lameness for a month. On the basis of clinical,
      radiographical, scintigraphical, computed tomographical and histopathological
      findings, aneurysmal bone cyst was diagnosed. Surgical curettage and bone cement
      treatment were applied. The patient recovered after 12 months. This case proves
      that aneurysmal bone cyst, without osteolysis and/or damages to the surrounding
      tissues, may result in a good prognosis if curettage and treatment with bone
      cement are done.

PMID- 15472482
TI  - Relationship between the sperm count and the fertilization rate of ova ovulated
      from the contralateral ovary in intrauterine horn insemination in cats.
AB  - Unilateral intrauterine horn insemination (UIUI) was carried out in cats, and we
      investigated the fertilization rate of ova ovulated from the contralateral ovary.
      Various numbers of sperm were used to inseminate the uterine horn on the side
      where ovulation was inhibited. The rates of conception were 1/11 (9.1%), 2/11
      (18.2%), and 5/7 (71.4%) in the 2 x 10(6), 4 x 10(6), and 8 x 10 (6) groups,
      respectively. Furthermore, the fertilization rate was 70.7% in the 8 x 10(6)
      group. Thus, ova ovulated from the contralateral ovary were not fertilized or the
      fertilization rate was low in some cats even when UIUI was performed with a large
      number of sperm.

PMID- 15472483
TI  - Clinical and histopathological findings in pustular psoriaform dermatitis
      (pityriasis rosea) in pigs.
AB  - Three cases of pustular psoriaform dermatitis (pityriasis rosea) in pigs were
      clinically and histopathologically examined. Grossly, the affected skin was
      characterized by multiple, circumscribed lesions. Three pigs were the descendants
      derived from the same Landrace boar. Skin lesions expanded centrifugally to
      became ring-shaped plaques. There were no abnormal values in hematological and
      serum biochemical profiles. Histopathologically, the epidermis showed remarkable
      thickening. The dermal lesions were characterized by a prominent component of
      superficial and deep perivascular infiltration of eosinophils. Dilatation of
      microvasculature was accompanied with congested vessels. These results revealed
      that the etiology of pustular psoriaform dermatitis in pigs was associated with a
      hereditary predisposition derived from the specific boars. This dermatosis is
      histopathologically characterized by microcirculatory disturbances with
      infiltration of abundant eosinophils.

PMID- 15472484
TI  - Fine mapping of the region including hypogonadism (hgn) locus on rat chromosome
      10.
AB  - The hypogonadic rat (hgn/hgn) shows male sterility, reduced female fertility, and
      renal hypoplasia, controlled by a single recessive gene located on rat chromosome
      10. We developed a fine map around the hgn locus using 565 rat backcross progeny
      and a Rat/Hamster radiation hybrid panel. The hgn locus was linked to Aldoc
      (aldolase c) and whn (winged helix of nude), and located in a 0.34-cM region
      between D10Rat30 and D10Rat68. The distance of the region was approximately 840
      kb on rat physical map. Neither loci responsible for male sterility nor renal
      hypoplasia has been mapped on the homologous regions of mouse chromosome 11 and
      human chromosome 17. Identification of the gene responsible for the hgn mutation
      would provide important information on urogenital development.

PMID- 15472485
TI  - Anaplastic ependymoma in the cervical spinal cord of a maltese dog.
AB  - An 8-year and 6-month-old female Maltese dog showed a stoop with rigidity of her
      cervix and back. Neurologic examination showed loss of proprioception, and
      deficiency of pain response. Postmortem examination revealed the neoplastic mass
      replacing the central area in the cervical spinal cord at the level from 4th to
      5th segments. Histologically, the mass was composed of neoplastic ependymal
      cells. The neoplastic cells showed marked atypism, and occasionally formed
      ependymal rosettes. Based on the morphologic features, the tumor was diagnosed as
      anaplastic ependymoma. Immunohistochemistry showed that the neoplastic cells were
      negative for glial fibrillary acid protein, and slightly positive for vimentin
      and cytokeratin.

PMID- 15472486
TI  - A case of shaker dog disease in a miniature dachshund.
AB  - A male miniature Dachshund, twenty-two months of age, was referred with
      paroxysmal generalized tremors as a main clinical sign. There were no
      abnormalities in the neurological examination except the lack of bilateral menace
      responses, and in the magnetic resonance imaging of its brain. Analysis of
      cerebro-spinal fluid revealed a slight rise in protein concentration and an
      increase in the number of cells. This case with brown hair was diagnosed as the
      shaker dog disease, which has also been well known as "little white shakers"
      syndrome due to being found in small dogs with white hair, because the clinical
      signs were exactly analogous to the shaker dog disease, and the generalized
      tremors disappeared on the first day after the administration of prednisolone and
      diazepam.

PMID- 15472488
TI  - Morphological observations of uterine and vaginal duplexes with a developmental
      anomaly at the vaginovestibular junction in a Japanese brown calf.
AB  - Since a rare anomaly of the female genital tract was defined as uterine and
      vaginal duplexes with a developmental anomaly at the vaginovestibular junction,
      it was morphologically examined in detail in a Japanese Brown calf. The genital
      tract was completely duplicated from the uterus to the vagina just cranial to the
      vestibule. At the vaginovestibular junction, a hymenal constriction and an
      aberrant location of the outer urethral orifice were also observed. These
      anomalies suggest that an error in the complete fusion of the Mullerian ducts and
      a failure in the correlated development between the Mullerian ducts and the
      urogenital sinus occurred in the embryonic stage.

PMID- 15472487
TI  - No effect of bovine interferon-tau for control of calf diarrhea and
      immunomodulation in calves.
AB  - Newborn calves received a low dose of bovine interferon-tau (boIFN-tau) orally
      for 4 weeks and calves that had developed diarrhea received a low dose of boIFN
      tau orally for 5 days. No effects of boIFN-tau were seen in the duration of the
      diarrhea, or in daily weight gain. Calves received a high dose of boIFN-tau
      subcutaneously 3 times and they were then stimulated with bovine herpesvirus type
      1 vaccine. No adverse effects were observed after the administration of boIFN-tau
      and lymphocyte subsets from calves did not change after the stimulation. Our
      results suggest that boIFN-tau does not seem protecting for preventing calves
      from diarrhea, recovering the health of calves with diarrhea or immunomodulation,
      although the treatment itself is not toxic.

PMID- 15472489
TI  - Odontogenic cysts in three dogs: one odontogenic keratocyst and two dentigerous
      cysts.
AB  - Odontogenic cysts, which showed cystic radiolucency in the jaw bone by
      radiographic examination and computed tomography, were enucleated by operation in
      3 dogs. One dog had a odontogenic keratocyst in the incisive bone of the right
      maxilla and another 2 cases revealed dentigerous cysts in the mandible. These
      cyst walls were enucleated or transpired by semiconductor laser. Afterwards,
      osteogenesis was confirmed at the defective part of jaw bone by extirpation of
      the cyst in all cases, and no recurrence has been noted in any cases. Odontogenic
      cyst is a disease which should be treated by surgical extirpation or
      transpiration.

PMID- 15472492
TI  - What time of day should I take my antihypertensive medications?

PMID- 15472494
TI  - A comparison of the efficacy and duration of action of telmisartan, amlodipine
      and ramipril in patients with confirmed ambulatory hypertension.
AB  - OBJECTIVES: The aim of the study was to compare the antihypertensive effects and
      the duration of action of telmisartan, amlodipine and ramipril in patients with
      mild-to-moderate hypertension using ambulatory blood pressure (ABP) monitoring.
      METHODS: After a 2-4-week single-blind, placebo run-in period, qualifying
      patients were randomized to receive telmisartan 80 mg (n=18); amlodipine 5 mg
      (n=22); titrated to 10 mg after 4 weeks; or ramipril 2.5 mg (n=17); titrated to 5
      mg and 10 mg after 1 and 3 weeks, respectively, administered once daily in the
      morning (0700 h). Ambulatory blood pressure monitoring was performed at baseline
      and at the end of the 8-week treatment period. Plasma renin activity was measured
      over 24 h at the same time points. RESULTS: Telmisartan and amlodipine provided
      significant reductions from baseline (P<0.0001) and not statistically different
      reductions between treatments in ABP during daytime (9.3/6.0 and 14.7/9.4 mmHg,
      respectively) and night-time (12.4/7.7 and 13.3/8.6 mmHg, respectively) at the
      end of 8 weeks' treatment. In contrast, although ramipril provided significant
      reductions in ambulatory systolic and diastolic BP from 2-6 h post dose (peak
      effect), it failed to induce significant reductions in mean daytime (4.5/1.6
      mmHg) and night-time (1.8/0.1 mmHg) ambulatory BP. In addition, the greater
      reductions in ABP with telmisartan and amlodipine were associated with a
      significant rise in plasma renin activity whereas ramipril only increased renin
      during the first 4 h of the administration interval. CONCLUSION: The results of
      the present study confirm the efficacy of both telmisartan and amlodipine in
      reducing ABP during each period of the 24-h interval. Because ABP reduction with
      ramipril was restricted to its peak effect, the present data do not support the
      use of this agent when administered once daily in the morning.

PMID- 15472495
TI  - Can improved software facilitate the wider use of ambulatory blood pressure
      measurement in clinical practice?
AB  - BACKGROUND: 24-h ambulatory blood pressure measurement (ABPM) is now recognized
      as being indispensable in the diagnosis and management of hypertension. The
      technique must, therefore, be made available in primary care, but in doing so it
      must be recognized that unfamiliarity with the technique may lead to
      misinterpretation of data. OBJECTIVE: To facilitate the wider application of
      ABPM, especially in primary care, we examined the features that would facilitate
      the development of a standardized user-friendly software program for the
      presentation, analysis and interpretation of data. METHODS AND RESULTS: The
      following features were considered essential to any software program for ABPM:
      standardized plots of 24-h profiles; computer interpretation of ABPM data and
      patterns; a user-friendly one-page report, flexible statistical analysis, and the
      facility to group data and to export data for audit and research analysis. The
      dabl ABPM program incorporating these features was introduced into the Blood
      Pressure Unit, Beaumont Hospital in 2000 and has been used in over 15 000 ABPM
      recordings. The program is now being used widely in general practice and
      specialized centres. CONCLUSIONS: It is feasible to design a software program to
      provide a standardized plotting format for ABPM, a basic analysis of data for day
      to-day clinical work, or elaborate analyses for research, and an interpretative
      report to assist diagnosis and to provide an educational process for doctors and
      nurses not familiar with the technique.

PMID- 15472497
TI  - Effects of systematic errors in blood pressure measurements on the diagnosis of
      hypertension.
AB  - OBJECTIVE: To estimate the effects of systematic errors in measurements of blood
      pressure on the diagnosis of hypertension. METHODS: We fitted regression curves
      to distributions of diastolic and systolic BP from recent Canadian and UK surveys
      and calculated the effect of systematic measurement errors on changes in the
      numbers of patients who would be classified hypertensive at thresholds of 85, 90
      and 95 mmHg diastolic and 140 and 160 mmHg systolic pressure respectively.
      RESULTS: Overestimation of diastolic BP by 5 mmHg increases the number of
      patients whose diastolic BP exceeds 85, 90 and 95 mmHg by 102, 132 and 166%
      respectively. Equivalent underestimation causes 57, 62 and 67% respectively of
      hypertensive patients to be missed. If systematic error in diastolic pressure is
      limited to +/-1 mmHg the diagnosis errors are between -15 and +23%.
      Overestimation of systolic BP by 3 and 5 mmHg increases the number classified as
      hypertensive by 24 and 43% respectively. Equivalent underestimation causes 19 and
      30% of patients with systolic hypertension to be missed. CONCLUSIONS: Small
      systematic errors in BP measurements may cause large variations in the proportion
      of patients diagnosed as hypertensive. To limit over- or under-diagnosis of
      diastolic hypertension to approximately 20%, systematic errors in diastolic BP
      measurements should be limited to 1 mmHg. An uncertainty of 3 mmHg may be
      adequate for detecting systolic hypertension.

PMID- 15472496
TI  - The second progress report on the Hypertension Objective treatment based on
      Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study.
AB  - BACKGROUND: The Hypertension Objective treatment based on Measurement by
      Electrical Devices of Blood Pressure (HOMED-BP) study is a large-scale
      intervention trial to determine both optimal target blood pressure (BP) on the
      basis of self-measured BP at home, and optimal initial antihypertensive
      medication. OBJECTIVE: To investigate the quality of randomization at the end of
      March 2003, and BP-controlled conditions during initial 6 months. METHODS: We
      evaluated the number of patients randomized by the end of March 2003, and BP
      changes during the initial 6 months based on intention-to-treat analysis.
      RESULTS: By the end of March 2003, a total of 1086 patients (12% of a planned
      randomization of 9000 patients) had been randomized. Among 653 patients who had
      been followed for > or =6 months after randomization, mean systolic/diastolic BPs
      at randomization in the calcium antagonist, angiotensin-converting enzyme and
      angiotensin II receptor blocker groups were 149/89, 150/89 and 149/88 mmHg,
      respectively. Blood pressures were reduced after 3 months (137/83, 139/82 and
      136/82 mmHg, respectively), and further reduced after 6 months (134/81, 135/80
      and 133/80 mmHg, respectively), with no significant differences identified
      between groups. In more- and less-intensive BP-lowering groups, mean
      systolic/diastolic BPs at randomization were 149/88 and 150/89 mmHg,
      respectively. Although BPs were reduced after treatment for 3 months (137/83 and
      137/82 mmHg, respectively) and 6 months (134/80 and 135/80 mmHg, respectively) in
      each target group, significant differences were still not observed between
      groups. CONCLUSIONS: Good quality of randomization was observed at the end of
      March 2003, but rate of achievement for target BPs was insufficient.

PMID- 15472498
TI  - Losing harmonic stability of arterial pulse in terminally ill patients.
AB  - OBJECTIVE: To measure the coefficient of variation of the harmonic magnitude
      (HCV) of the radial arterial pulse before death of cancer patients. METHODS: We
      non-invasively recorded the radical arterial pulse of 21 end-stage cancer
      patients, 31 healthy subjects, and 47 outpatient department (OPD) patients.
      During the 2-week study, eight cancer patients expired. RESULTS: There were no
      considerable differences in diastolic or systolic blood pressure between cancer
      patients and other subjects; however, all six HCVs were significantly higher in
      the cancer patients (P<0.05). Within the cancer patient group, the first and
      second HCV were notably higher in the patients that expired (P<0.05), and the
      first to fourth HCVs were significantly increased on their last day (P<0.05). In
      the control healthy subjects and the OPD group, the HCVs were below 5 and 8%,
      respectively. In the cancer patients, the third to sixth HCVs were higher than
      15%. On the last day of the cancer patients that expired, even the first and
      second HCVs were higher than 15%. CONCLUSIONS: During the dying process, the
      traditional diastolic and systolic blood pressure did not show significant
      changes; however, all the harmonic components gradually lost their stability. The
      HCVs, which increased first for the high-frequency components and then the low
      frequency components, could quantitatively reflect the severity of different
      stages of illness.

PMID- 15472499
TI  - Linear dynamic features of ambulatory blood pressure in a population-based study.
AB  - BACKGROUND: The objective of the present study was to characterize inter
      individual variation in traits that measure linear dynamic features of ambulatory
      blood pressure (BP) measurements that may be used in future population studies to
      investigate the relationships between variation in genetic and environmental
      factors that influence BP regulation and risk of hypertension, and among
      hypertensives, provide new insights into variation in risk of target organ
      damage. DESIGN: We obtained ambulatory BP measurements every 10 min over a 24-h
      period in 199 healthy non-Hispanic Whites (84 females, 115 males) from Rochester,
      Minnesota, USA. METHODS: We then used the autocorrelation function (ACF) to
      measure linear dynamic features of the daytime and night-time observations in
      females and males separately. Re-sampling procedures were used to test whether
      these individuals had significant linear dependencies. RESULTS: We found that
      systolic and diastolic ambulatory BP measurements in our sample have
      statistically significant linear dependencies and that the ACFs are approximately
      normally distributed among individuals. In addition, we found that the
      distributions of the ACF traits among individuals are not significantly
      correlated with the mean of the ambulatory BP measurements, are different in men
      and women, and are different during the daytime versus the night-time.
      CONCLUSIONS: We conclude that ACF traits are different measures of BP than the
      mean that capture information about the biology of BP regulation reflected in the
      dynamics of a person's minute-to-minute and hour-to-hour BP phenotype. Studies of
      measures of linear dynamic features of BP are likely to offer new insights into
      the genetic and environmental factors that contribute to inter-individual
      variation in BP regulation and risk of future hypertension as well as new
      insights into the causes of variation in risk of target organ damage in
      individuals with established hypertension.

PMID- 15472500
TI  - Accuracy of automated auscultatory blood pressure measurement during supine
      exercise and treadmill stress electrocardiogram-testing.
AB  - OBJECTIVES: Monitoring of brachial blood pressure during exercise
      electrocardiogram (ECG) testing is mandatory and changes in blood pressure (BP)
      can provide critical management evidence. Patient movement, mechanical vibration,
      artifactual sounds and observer variability make standard manual techniques
      problematic. This was an investigator-initiated study to assess an automated
      auscultatory technique of BP assessment [Tango exercise blood pressure monitor
      (SunTech Medical Instruments, NC, USA)] to adequately measure BP during stress
      ECG testing. METHODS: Initially five fit young male volunteers underwent invasive
      right brachial artery BP recording using a low-compliance fluid-filled catheter
      with simultaneous manual and automated assessment. Secondarily, during exercise
      ECG testing, the system was assessed against beat-to-beat brachial blood
      pressures obtained from a catheter-tip solid-state pressure manometer positioned
      in the ipsilateral brachial artery. RESULTS: In the supine study overall mean
      difference (+/-SEM) between invasive and manual blood pressures was 3.26 (1.53)
      and 3.89 (1.90) mmHg for diastolic BP (DBP) and systolic BP (SBP) respectively.
      Corresponding differences between invasive and automated results, and manual and
      automated were 3.68 (0.84) and -7.31 (1.83) mmHg, and -0.64 (+/-1.43) and -11.42
      (+/-1.59) mmHg. During treadmill exercise-ECG testing the combined mean
      difference (+/-SEM) between invasive and automated SBP and DBP was 4.79 (+/-0.14)
      and 6.33 (+/-0.10) mmHg, respectively. CONCLUSION: Automated BP assessment during
      exercise-ECG testing is feasible with the use of appropriate automatic devices
      likely to be at least as accurate as manual BP registration. The Tango device is
      tolerant to exercise and provides reliable automatic BP assessment with absolute
      differences within an acceptable clinical range.

PMID- 15472501
TI  - Non-invasive measurement of cardiac output in patients with chronic heart
      failure.
AB  - OBJECTIVES: The measurement of cardiac output by thoracic bioimpedance has been
      previously assessed in several studies. However, there continues to be
      disagreement as to whether this technique is sufficiently accurate for use in
      clinical practice or research. The current study aimed to compare thoracic
      bioimpedance (COTB) with thermodilution (COTD) in patients with stable chronic
      heart failure. METHODS AND RESULTS: A total of 282 paired measurements of cardiac
      output from 11 patients were analysed. There was good correlation between COTB
      and COTD (r=0.76, P<0.0001). However, Bland-Altman analysis revealed an average
      difference between values of 0.3 (2.2) l/min (P=0.02), suggesting a small average
      bias but marked variability in results. There was no significant correlation when
      results were expressed as percentage change from baseline and a significant
      average difference between values of 10.1 (30.1)%. There was no difference in
      between-day repeatability between thermodilution and thoracic bioimpedance [-0.2
      (1.2) versus 0.1 (1.0) l/min, P=0.7]. CONCLUSIONS: This study demonstrates a
      correlation between the techniques but shows a poor level of agreement. The
      method of COTB underestimated cardiac output compared with COTD, and this
      difference appeared greater with higher cardiac outputs. Agreement was worse when
      results were expressed as change from baseline. The present study does not
      support the use of thoracic bioimpedance in its current form as an alternative to
      thermodilution in stable patients with chronic heart failure.

PMID- 15472507
TI  - Could immunosuppressive drugs reduce recurrence rate after second resection for
      Crohn disease?
AB  - BACKGROUND: The aim of this study was to assess the possible benefit of
      postoperative immunosuppressive drugs administration (ie, azathioprine, 6
      mercaptopurine, or methotrexate) on long-term surgical recurrence rate after
      second anastomotic ileocolonic resection. METHODS: From 1984 to 2000, 26 patients
      with CD underwent second resection for ileocolonic anastomotic recurrence. There
      were 14 women and 12 men (mean age +/- SD: 34 +/- 9 years). Two groups of
      patients were compared according to the postoperative treatment:
      immunosuppressive (IS) drugs group was composed of 14 patients, and control group
      was composed of 12 patients receiving either salicylates (n = 5) or no treatment
      (n = 7). RESULTS: Clinical recurrence rate at 3 years was significantly lower in
      the IS group than in the control group (3/12, 25% vs 6/10, 60%; P < 0.05).
      Although not significant, after a mean follow-up of 80 +/- 46 months (extr. 17
      178 months) after the second resection, clinical recurrence rate at follow-up was
      also lower in IS group (6/14, 43%) than in control group (9/12, 75%). The mean
      delay of recurrence was similar in both groups (27 +/- 13 months vs 28 +/- 21;
      NS). A third intestinal resection was performed less frequently in the IS group
      than in control group (2/14, 17% vs 7/12, 58%; P < 0.02). CONCLUSIONS: In
      patients treated with IS drugs, the rate of postoperative recurrence after second
      ileocolonic CD resection is lower than in untreated patients. Our results suggest
      that IS drugs should be evaluated prospectively for prevention of second
      postoperative CD recurrence.

PMID- 15472508
TI  - Prospective evaluation of intestinal homing memory T cells in ulcerative colitis.
AB  - BACKGROUND: Intestinal homing (beta7+) memory T cells reflect the mucosal
      environment in which they were primed. We hypothesized that prospective
      assessment of cytokine production by intestinal homing (beta7+) memory T cells in
      ulcerative colitis patients followed from remission to early relapse may
      elucidate shifts in cytokine production relevant to the mucosal environment
      associated with the early phase of inflammation. METHODS: Twelve patients with
      frequently relapsing ulcerative colitis (> or = 2 relapses in the previous 12
      months) were recruited in remission and followed prospectively until relapse.
      Antibody labeling of whole blood and flow cytometry were used to identify beta7+
      cells and beta7- populations within CD3+CD45RA- leukocytes. Production of
      cytokines (IFN-gamma, TNF-alpha, IL-2, IL-10, TGF-beta, and IL-4) was determined
      by intracellular labeling. RESULTS: Early relapse of ulcerative colitis was
      associated with a shift of T cells from the naive to the memory T cell pool, and
      further the ratio of beta7+:beta7- memory T cells was significantly reduced at
      relapse (p < 0.01). A greater proportion of intestinal homing beta7+ memory T
      cells produced IL-4 (p < 0.02) and TNF-alpha (p < 0.05) at disease relapse
      compared with remission. Non-intestinal homing beta7- memory T cells also showed
      a tendency toward an increased production of TH1 and TH2 cytokines. CONCLUSIONS:
      The earliest phase of intestinal inflammation in ulcerative colitis patients is
      associated with an increase in both TH1 (TNF-alpha and TH2 (IL-4) cytokines by
      intestinal homing beta7+ memory T cells. These data support the principles of
      targeting lymphocyte trafficking as therapies in ulcerative colitis.

PMID- 15472509
TI  - Characterization and distribution of colonic dendritic cells in Crohn's disease.
AB  - Dendritic cells (DCs) are thought to play an important role in the pathogenesis
      of autoimmune inflammation, including Crohn's disease (CD). We investigated the
      distribution and state of maturation of DCs in the colon in relation to the
      severity of inflammation and therapy. Using archival specimens from colonic
      resections in 19 pediatric patients with CD and 14 controls, we identified and
      characterized the DCs within the lamina propria, submucosa, and muscularis
      compartments using morphologic and quantitative immunohistochemical methods. The
      distribution of CD11c+CD83+CD68+DC-SIGN+ and immature CD11c+CD83-CD68-DC-SIGN+
      DCs within the different compartments varied according to the presence or absence
      of CD as well as to the severity of inflammation and systemic corticoid
      treatment. Immature DCs were only found in non-inflamed control colonic tissue.
      Marked reductions (60% and 30%) in total CD11c and CD83 DC numbers were observed
      in CD tissue samples compared with controls (P < 0.05). CD samples from patients
      on corticosteroid therapy were significantly more depleted than in tissue from
      untreated patients or those on other drugs. Colonic tissue with severe
      inflammation had reduced numbers of CD11c+ and CD83+ DCs in the lamina propria
      and submucosal compartments (80% and 76% for CD11c; 75% and 76% for CD83,
      respectively, P < 0.05), with a concomitant increase (525% for CD11c and 700% for
      CD83 P < 0.05) of DCs in the muscularis compartment, compared to moderately
      inflamed and non-inflamed CD tissue. Our data suggest that an imbalance in
      intestinal DC subpopulations may play a role in the initiation and/or the
      maintenance of chronic inflammation in CD. Corticosteroid therapy is associated
      with colonic DC depletion.

PMID- 15472510
TI  - A genome scan in 260 inflammatory bowel disease-affected relative pairs.
AB  - We report genome-wide linkage results using model-free linkage analysis (Allegro)
      of 358 autosomal microsatellites in 260 new inflammatory bowel disease-affected
      relative pairs from 139 Caucasian families, including 108 Crohn's disease
      affected relative pairs and 72 ulcerative colitis-affected relative pairs. Our
      results provide confirmatory evidence for linkage between the IBD2 locus and the
      inflammatory bowel disease phenotype (lod = 2.12 at GATA91H06) and ulcerative
      colitis phenotype (lod = 1.44 at GATA91H06), but not the Crohn's disease
      phenotype. We also find confirmatory evidence for linkage between the IBD3 locus
      and Crohn's disease (lod = 2.26 at D6S2439) but not ulcerative colitis or
      inflammatory bowel disease. We find nominal evidence for linkage of inflammatory
      bowel disease to loci on chromosome 6q (lod = 2.21 between D6S2436/D6S305), 8q
      (lod = 1.57 between D8S1113/D8S1136), 15q (lod = 2.02 between D15S652/D15S816),
      and 22 (lod = 1.50 at D22S689); of Crohn's disease to loci on chromosome 5q
      approximately 50 centiMorgans centromeric from IBD5 (lod = 1.69 at D5S1501) and
      15q (lod = 1.82 at D15S652); and of ulcerative colitis to a locus on chromosome
      2q (lod = 2.19 between D2S1776/D2S1391). The inflammatory bowel disease linkage
      peak on chromosome 6q is located in the same general region that showed nominal
      evidence for linkage to IBD in a Belgian genome scan, and the ulcerative colitis
      linkage peak on chromosome 2q is located in the same general region that showed
      nominal evidence for linkage to the inflammatory bowel disease, Crohn's disease,
      or ulcerative colitis phenotypes in four other European/North American genome
      scans.

PMID- 15472511
TI  - Disease location, anti-Saccharomyces cerevisiae antibody, and NOD2/CARD15
      genotype influence the progression of disease behavior in Crohn's disease.
AB  - BACKGROUND: Crohn's disease (CD) is characterized by heterogeneity of phenotype.
      The Vienna classification can be used to classify CD, and recent data illustrate
      that behavior evolves over the course of the disease. Clinical and biological
      influences on disease progression remain unclear. We examined the associations of
      CD disease progression at diagnosis and for up to 20 years of follow-up. METHODS:
      Two hundred thirty-one well-characterized CD patients were studied. Demographic,
      clinical, and NOD2/CARD15 data were collected. Disease behavior according to the
      Vienna classification was assessed at diagnosis and for up to 20 years following
      diagnosis. RESULTS: At diagnosis, 70% of patients had inflammatory disease, 9%
      stricturing, and 21% penetrating. Early age at diagnosis was associated with
      ileocolonic and upper GI disease (p = 0.015), and positive anti-Saccharomyces
      cerevisiae antibody (ASCA) was associated with ileal involvement (p = 0.008).
      Smoking was relatively protective against colonic, rather than ileal involvement
      at diagnosis (p < 0.02). At 20 years, 92% had progressed to a more severe disease
      type. Patients who progress to a more severe disease type require more frequent
      surgery (p < 0.00001). Multivariate analysis found disease progression to be
      associated with ileal disease location (p = 0.001) and positive ASCA (p = 0.003).
      Variant NOD2/CARD15 alleles were protective against rapid progression of disease
      phenotype (p = 0.04). The presence of perianal disease was independent of
      intestinal penetrating disease. CONCLUSIONS: The progression of disease type in
      CD is associated with the need for more frequent surgery. Rapid progression is
      associated with ileal disease and positive ASCA, and delayed progression is
      associated with variant NOD2/CARD15 alleles. Consideration should be given to a
      separate Vienna classification for perianal disease.

PMID- 15472512
TI  - Intracellular polyamine levels of intestinal epithelial cells in inflammatory
      bowel disease.
AB  - Polyamines and their acetylated derivatives are a prerequisite for cellular
      metabolism and considered to be essential for proliferation and differentiation
      of the rapidly renewing intestinal mucosa. However, their role during mucosal
      inflammation is less clear. Polyamine concentrations were determined in isolated
      colonic epithelial cells (CECs) from endoscopic biopsies from 26 patients with
      inflammatory bowel disease (IBD) and 40 controls as well as colon samples from
      mice with and without acute or chronic dextran sodium sulfate (DSS)-induced
      colitis. In patients with ulcerative colitis, CEC spermidine and N8
      acetylspermidine levels were significantly enhanced and spermine levels were
      reduced compared with healthy controls. A correlation of polyamine levels of
      patients with IBD with their corresponding inflammatory index revealed that
      increased concentrations of spermidine, N8-acetylspermidine, and N1
      acetylspermine were found in CECs from the most severe inflamed mucosal areas.
      Using acute and chronic DSS colitis as a model of mucosal inflammation, we found
      enhanced levels of spermidine and spermine in acute colitis, whereas in chronic
      inflammation, CEC spermine concentrations were decreased. Our data indicate a
      lack of the anti-inflammatory polyamine spermine in severe ulcerative colitis and
      chronic DSS colitis, which may aggravate the disease. Increased spermidine and N8
      acetylspermidine levels reflect increased uptake and metabolism likely due to
      accelerated proliferation and regeneration of CECs.

PMID- 15472513
TI  - Prevention of fibrosis in experimental colitis by captopril: the role of tgf
      beta1.
AB  - BACKGROUND & AIMS: There is a body of evidence to suggest that the local
      activation of angiotensin II (ANG II) plays a pivotal role in fibrogenic response
      involving the kidney, heart, lung, pancreas and liver. In such conditions,
      fibrosis is mediated, at least partially, through ANG II induction of the
      cytokine transforming growth factor-beta1 (TGF-beta1). Both ANG II and TGF-beta1
      also seem to be involved in intestinal fibrosis and stenosis, particularly in
      Crohn's disease. The aim of the present study was, firstly, to determine the
      effects of the angiotensin-converting enzyme inhibitor, captopril, on colonic
      fibrosis in experimental colitis in rats and, secondly, to check the role of TGF
      beta1 on these effects. METHODS: Colitis was induced in rats by intracolonic
      administration of TNBS. Colonic fibrosis was assessed 21 days later by
      macroscopic and microscopic evaluation. Levels of collagen alpha1 gene
      expression, hydroxyproline, angiotensin II and TGF-beta1 proteins, and TGF-beta1
      mRNA were measured on the colonic tissue. RESULTS: In chronic colitis, captopril
      significantly reduced the score of macroscopic and histologic lesions, as well as
      the colonic tissue levels of collagen alpha1, hydroxyproline, ANG II and TGF
      beta1 proteins, and TGF-beta1 mRNA. CONCLUSIONS: These data demonstrate for the
      first time that the prophylactic administration of captopril is effective in
      preventing colonic fibrosis in TNBS-induced colitis. The antifibrotic action of
      captopril could be due to the blockade of TGFbeta-1 overexpression, and/or to a
      direct down-regulation of TGFbeta-1 transcript.

PMID- 15472514
TI  - Altered immune system glycosylation causes colitis in alpha1,2-fucosyltransferase
      transgenic mice.
AB  - BACKGROUND AND AIMS: Altered glycosylation of the mucosal barrier has been
      proposed as a primary defect in the pathogenesis of IBD. Glycosylation defects
      however may also have a profound influence on immune function. Mice transgenic
      for human alpha1,2-fucosyl-transferase (hFUT1) have widespread disturbances in
      cell surface glycosylation and spontaneously develop colitis. The aims of this
      study were to characterize colitis in hFUT1 mice and to determine whether
      glycosylation-induced changes of the mucosal barrier or the immune system were
      critical for its pathogenesis. METHODS: The pathologic features of hFUT1
      transgenic mice were characterized. The mucosal barrier was assessed by lectin
      binding and permeability studies. T-cells and the thymus were assessed by FACS
      analysis and histology. To isolate the hFUT1 mucosal barrier from the hFUT1
      immune system, bone marrow chimeras were generated. RESULTS: Seventy percent of
      hFUT1 mice raised in SPF conditions developed histologic evidence of colitis. The
      mucosal barrier demonstrated altered glycosylation but intestinal permeability
      was preserved. HFUT1 mice were profoundly lymphopenic, with aberrant T-cell
      markers and thymic medullary hypoplasia. Reconstitution with wild type bone
      marrow restored thymic morphology and prevented colitis in hFUT1 mice.
      CONCLUSION: Altered glycosylation in hFUT1 mice has a profound influence on T
      cell development and this defect, rather than a mucosal barrier defect, is
      crucial for the development of colitis.

PMID- 15472515
TI  - Interleukin-10 knockout mouse: a model for studying bone metabolism during
      intestinal inflammation.
AB  - The objective was to compare bone mass (bone mineral content [BMC], bone mineral
      density [BMD]) and biomechanical strength of femurs and lumbar vertebrae from
      male and female wild-type (WT) and IL-10 knockout (KO) mice to determine if the
      IL-10 KO mouse model is appropriate for studying inflammation-associated bone
      abnormalities and potential interventions. Offspring from IL-10 KO and WT mice (n
      = 15 to 19 mice/gender per group) were studied until 13 weeks of age. IL-10 KO
      mice had a higher (P < 0.05) colonic histologic injury score and serum
      proinflammatory cytokines (IL-6, IL-1beta, TNF-alpha) than WT mice. IL-10 KO mice
      also experienced bone abnormalities as femur and verterbral BMC and BMD were
      lower (P < 0.05) compared with WT mice. Moreover, some biomechanical strength
      parameters such as femur yield load (P = 0.057) and resilience (P < 0.05) and
      peak load of lumbar vertebra 3 (P < 0.05) were lower than WT mice. Due to
      differences in body size, males had greater (P < 0.05) femur and vertebral bone
      mass as well as femur weight, length, yield load, resilience, and peak load than
      females. A significant interaction (genotype x gender) was only observed for
      femur resilience in which male WT mice had a greater (P = 0.009) resilience than
      all other groups. These results demonstrate that IL-10 KO mice develop bone
      abnormalities that accompany intestinal inflammation and elevated serum
      proinflammatory cytokines. Thus, the IL-10 KO mouse model may be useful for
      studying inflammation-associated bone abnormalities and potential therapeutic
      interventions.

PMID- 15472516
TI  - Catalposide, a compound isolated from catalpa ovata, attenuates induction of
      intestinal epithelial proinflammatory gene expression and reduces the severity of
      trinitrobenzene sulfonic Acid-induced colitis in mice.
AB  - Certain irinoid-producing plants have been used as herbal anti-inflammatory
      remedies. Here we evaluated whether catalposide (CATP), a single compound
      isolated from irinoid-producing plant Catalpa ovata, has a potential for
      preventing or ameliorating diseases characterized by mucosal inflammation.
      Preliminary microarray-based gene expression test revealed that CATP, which alone
      did not significantly affect expression of any of the >8,000 genes analyzed,
      attenuated the expression of tumor necrosis factor-alpha (TNF-alpha)-induced
      proinflammatory genes including interleukin-8 (IL-8) in human intestinal
      epithelial HT-29 cells. Down-regulation of IL-8 mRNA accumulation was also
      reflected by the decreased IL-8 secretion in CATP-treated HT-29 cells. The signal
      transduction study revealed that CATP significantly attenuates TNF-alpha-mediated
      p38 and extracellular signal-regulated kinase (ERK) phosphorylation. Further,
      CATP reduced NF-kappaB-mediated transcriptional activation as well as Ikappa
      Balpha degradation. To establish the in vivo relevance of these findings, we
      examined whether CATP could affect intestinal inflammation in vivo using the
      mouse model of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis.
      Intrarectal administration of CATP dramatically reduced the weight loss, colonic
      damage, and mucosal ulceration that characterize TNBS colitis. Moreover, CATP
      suppressed the expression of TNF-alpha, interleukin-1beta, and intercellular
      adhesion molecule-1 along with the inhibition of NF-kappa B p65 translocation
      into nucleus in TNBS colitis. Collectively, current results demonstrate that CATP
      may be an effective agent for the treatment of diseases characterized by mucosal
      inflammation.

PMID- 15472517
TI  - Serum bFGF and VEGF correlate respectively with bowel wall thickness and
      intramural blood flow in Crohn's disease.
AB  - Serum levels of basic fibroblast growth factor (bFGF) and vascular endothelial
      growth factor (VEGF)--two factors known to promote tissue repair, fibroblast
      proliferation, and angiogenesis--were measured in Crohn's disease patients and
      correlated with bowel wall thickness (BWT), measured by conventional grey scale
      ultrasonography, and with the ileal intramural vessel flow, measured by contrast
      enhanced color Doppler imaging. Serum samples were obtained from 25 patients with
      active Crohn's disease and 22 healthy volunteers, all sex- and age-matched. Serum
      bFGF and VEGF levels were measured by ELISA assay. All the patients were examined
      with conventional transabdominal bowel sonography. Color Doppler of the
      intramural enteric vessels was then performed after the intravenous injection of
      Levovist, a galactose-based sonographic contrast agent. In Crohn's disease
      patients, serum bFGF and VEGF were significantly higher compared with healthy
      volunteers. A positive correlation between serum bFGF and BWT and between serum
      VEGF and color Doppler signal intensity was found. The raised serum bFGF levels
      in Crohn's disease patients with intestinal strictures compared with patients
      with other phenotypes (fistulizing, inflammatory), together with the correlation
      observed between serum bFGF and BWT, suggests a possible involvement of bFGF in
      the process of transmural fibrogenesis in Crohn's disease. The higher levels of
      VEGF in those patients with increased intramural blood flow suggests that VEGF
      may be considered a marker of angiogenesis in this condition.

PMID- 15472518
TI  - Identification of budesonide and prednisone as substrates of the intestinal drug
      efflux pump P-glycoprotein.
AB  - Steroid resistance is a major problem in the management of patients with
      inflammatory bowel disease. In Crohn disease, poor response to corticosteroids
      has been related to increased expression of the drug efflux pump, P-glycoprotein.
      However, it has not been investigated thoroughly whether corticosteroids commonly
      used for drug therapy in inflammatory bowel disease are substrates of P
      glycoprotein. We tested the hypothesis that budesonide and prednisone are
      substrates of P-glycoprotein thereby possibly contributing to variable
      therapeutic effects. Polarized, basal to apical transport of [3H]budesonide and
      [3H]prednisone was studied in monolayers of L-MDR1 cells (LLC-PK1 cells stably
      transfected with human MDR1 cDNA) and Caco-2 cells, both of which express P
      glycoprotein in their apical membrane. Drug transport was measured during 4 hours
      at substrate concentrations of 5 microM. Net transport rates and permeability
      coefficients were calculated. Inhibition of P-glycoprotein-mediated transport
      across Caco-2 monolayers was determined after addition of the P-glycoprotein
      inhibitor PSC-833. The net transport rate from the basolateral to the apical side
      was significantly higher in L-MDR1 than in LLC-PK1 cells for both budesonide and
      prednisone. Apparent permeability coefficients of budesonide and prednisone
      reflected polarized transport from basal to apical. PSC-833 inhibited the
      polarized transport of both corticosteroids. In conclusion, budesonide and
      prednisone were identified as substrates of the intestinal drug efflux pump, P
      glycoprotein. Therefore, drug secretion via P-glyco-protein into gut lumen might
      play a more important role in pharmacokinetics and pharmacodynamics of these
      corticosteroids than currently appreciated in gastroenterological practice.

PMID- 15472519
TI  - Annexin 1 is secreted in situ during ulcerative colitis in humans.
AB  - Although annexin l exerts extracellular anti-inflammatory properties, little is
      known about its release in inflammatory diseases. Here, we characterized annexin
      1 secretion in ulcerative colitis (UC) patients. Annexin 1 was detected by
      immunoblotting, in tissue homogenates and supernatants of colonic biopsies
      incubated in culture media, and in luminal colonic perfusates of UC patients.
      Annexin 1 was released by inflamed colonic biopsies from patients having severe
      UC but not by biopsies from healthy colon of the same patient or by biopsies from
      non-UC patients or from patients with slight or moderate UC. Annexin 1 was
      detected in luminal colonic perfusates of patients having moderate or slight UC
      but not in perfusates from control patients. The level of annexin 1 expression
      and secretion was unrelated to long-term glucocorticoid treatment, but annexin 1
      secretion in perfusates was induced, in some patients, by short-term
      glucocorticoid exposure. These results show that annexin 1 is secreted
      endogenously in the colon of patients with UC. This secretion, which occurs both
      in vitro and in vivo, depends on the severity of inflammation. Given the anti
      inflammatory effects of annexin 1, this protein may serve to down-regulate the
      inflammatory response in the course of inflammatory bowel disease.

PMID- 15472520
TI  - Intestinal interleukin-13 in pediatric inflammatory bowel disease patients.
AB  - BACKGROUND: Interleukin-13 (IL-13) is a multifunctional cytokine whose net
      principle action is to diminish inflammatory responses. Dysregulation of IL-13
      production has been proposed to contribute to intestinal inflammation in
      inflammatory bowel disease (IBD) patients. Previous studies implicate IL-13 in
      IBD pathogenesis; however, they fail to accurately reflect in vivo intestinal IL
      13 production. We evaluate IL-13, IL-6, and IL-1beta elaborations from colonic
      organ cultures of pediatric IBD patients METHODS: Endoscopic lamina propria
      biopsies or surgical specimens from pediatric patients with IBD were organ
      cultured and supernatants evaluated by enzyme-linked immunosorbent assay for IL
      1beta, IL-6, and IL-13. RESULTS: IL-13 concentrations were significantly reduced
      in ulcerative colitis (UC) patients when compared with normal controls (P =
      0.002) and Crohn disease (CD) patients (P = 0.001). End-stage UC patients at
      colectomy had lower intestinal IL-13 production than all other UC patients (P =
      0.002). No significant correlation was found between IL-13 concentration and
      histologic disease severity (P = 0.134). CONCLUSIONS: Diminished intestinal IL-13
      production is present in UC patients and wanes further with clinical disease
      progression. These findings suggest that UC patients may be differentiated from
      CD patients by intestinal IL-13 quantitation, and UC patients may benefit from IL
      13 enhancing therapies.

PMID- 15472521
TI  - Patterns of complementary and alternative medicine use in a population of
      pediatric patients with inflammatory bowel disease.
AB  - Complementary and alternative medicine use is prominent in the United States. The
      use of complementary and alternative therapies appears to be common in patients
      with inflammatory bowel disease, but few studies have been completed in children.
      We sought to examine the extent that children with inflammatory bowel disease in
      the Greater Philadelphia area (Philadelphia County and the surrounding counties
      in Delaware, New Jersey, and Pennsylvania) use alternative therapies. We paid
      particular attention to the specific types of therapies used and whether certain
      demographic and disease associated factors influence the degree of usage. In this
      study, we questioned the families of all children diagnosed with inflammatory
      bowel disease, aged 6 to 16 years and living within Philadelphia and its
      surrounding counties, who were followed at 1 of the 2 academic pediatric
      gastroenterology programs that served the area. More than 80% of surveys were
      returned. Fifty-one percent (95% C.I. 45% to 56%) of patients surveyed reported
      some form of alternative medicine use within the previous year. Univariate
      analysis revealed increased use among patients who had Crohn disease, who used
      the Internet for research on their disease, who reported poor quality of life and
      had increased school absences in the past year. Therapies associated with
      alternative medicine use included biological and immunomodulatory therapy.
      Regression analysis revealed positive associations between use of alternative
      therapies and expenditure on nonprescription treatments, poor quality of life,
      Internet research, and the need for calorie supplementation, whereas there was a
      negative association with history of prior surgery for inflammatory bowel
      disease.

PMID- 15472522
TI  - Serum p53 antibodies in patients affected with ulcerative colitis.
AB  - During tumor progression, the accumulation in genetic alterations is a
      fundamental characteristic of malignant cells. p53 gene is frequently mutated in
      human tumor. Cellular accumulation of p53 protein can initiate an immune response
      with generation of circulating anti-p53 antibodies. Patients with ulcerative
      colitis have an increased risk of developing colorectal neoplasm and, among the
      different genes involved in carcinogenesis, p53 may play a key role. Sera and
      tissues from 97 patients (M = 53, F = 44) affected with ulcerative colitis (UC)
      were collected. Serum anti-p53 antibodies (p53Abs) were detected in duplicate
      with ELISA method. Serum p53Abs were detectable in 9.3% (9/97) of patients
      affected with UC. In these patients, the titer of p53Ab ranged between 3.1 and
      14.9 U/mL (mean, 6.6 U/mL; SD, 4.64). Serum p53Abs were undetectable in control
      group. With an immunoluminometric assay for the quantitative determination of
      p53, we found 9/97 positive samples (> or = 0.69 mg/mg of total proteins). In
      contrast, the samples of the remaining 89 patients were found negative (< or =
      0.30 mg/mg of total proteins). All patients that were positive for anti-p53
      antibodies were also positive with p53 protein accumulation in the tissue of
      colonic biopsies. In UC, follow-up with colonoscopy has several advantages. The
      colonoscopy is not well accepted by patients, and poor patient observance has the
      potential to seriously devalue the technique as a screening tool, despite
      practical considerations of competence within endoscopy service. Serological
      detection of p53Abs by enzyme-linked immunosorbent assay (ELISA) is easy to
      perform, does not require tumor specimen, can be performed in a routine
      diagnostic procedure, may be used in clinical practice, and could facilitate
      physicians in patient monitoring. We suggest that serum p53Abs assessment,
      indirect marker for p53 gene mutations, and abnormally high p53 protein levels
      could be considered to have a potential for use as a complementary test to
      improve surveillance program performance.

PMID- 15472523
TI  - Anxiety, functional health status, and coping ability in patients with ulcerative
      colitis who are undergoing colonoscopic surveillance.
AB  - BACKGROUND: Patients with long-standing extensive ulcerative colitis (UC) have an
      increased risk of developing colorectal cancer (CRC). High-risk UC patients are
      nowadays enrolled in surveillance programs to decrease CRC incidence and
      mortality, although little is known about patients' concerns and anxiety when
      subjected to colonoscopic surveillance. The aims of this study were to evaluate
      functional health status, general state of health, anxiety, and coping ability in
      patients with UC taking part in such a program in a university hospital setting.
      METHODS: Forty-one patients with long-standing, extensive/total UC in remission
      (median disease duration, 21.0 years) undergoing surveillance comprised the study
      group. Twenty patients with extensive disease but with shorter disease duration
      (median, 8.0 years) and 19 patients with only distal involvement UC acted as
      controls. Four different self-administered questionnaires (SAQs) were used. The
      SAQ assessments were made twice in the study group and once in the controls.
      RESULTS: No statistically significant differences were found in any of the SAQ
      assessments. The median scores obtained were well within the ranges seen in
      normal healthy subjects. CONCLUSIONS: Colonoscopic surveillance in long-standing
      UC does not seem to generate increased anxiety or impairment of functional or
      general health status among participating patients. Rather, UC patients in
      clinical remission seem to cope just as well as healthy individuals irrespective
      of the CRC risk or surveillance procedures.

PMID- 15472524
TI  - Impaired gastric acid and pancreatic enzyme secretion in patients with Crohn's
      disease may be a consequenece of a poor nutritional state.
AB  - INTRODUCTION: Impaired pancreatic function has been reported in Crohn's disease,
      the cause of which is uncertain. This study investigated the effect of
      malnutrition, and subsequent re-feeding, on digestive function and protein
      synthesis in Crohn's disease patients. METHODS: Gastric acid and pancreatic
      secretion studies were performed on malnourished Crohn's patients before, and
      after a period of intensive nutritional support. Whole body, as well as
      pancreatic enzyme protein synthesis was investigated by [14C]leucine isotope
      incorporation studies. Results were evaluated in comparison to normal healthy
      volunteers. RESULTS: The mean body mass index (BMI) of the Crohn's patients was
      14.14 kg/m2. The Crohn's patients had reduction in the secretion of gastric acid
      (7.36 versus 25.53 mEq/h; P < 0.01), and the pancreatic enzymes, amylase (759.6
      versus 2305 U/h; P < 0.01), lipase (33.01 versus 118.6 U/h; P < 0.01) and trypsin
      (97.43 versus 341.4 U/h; P < 0.01). Resting energy expenditure (REE), expressed
      in relation to body mass, was greater in the malnourished Crohn's disease
      patients (38.25 versus 25.36 kcal/kg/d; P = 0.01). Total body protein synthesis
      was reduced (2.82 versus 4.39 g protein/kg/d; P < 0.05), with significant
      impairment in the synthesis of pancreatic enzymes, and reduction of zymogen
      stores. Following re-feeding, the BMI of the Crohn's patients improved to 16.80
      +/- 0.66 kg/m2. Pancreatic enzyme synthesis improved, with significant increase
      in pancreatic enzyme stores and secretion, to levels similar to control values.
      Gastric acid secretion also improved, although still lower than the control
      value. CONCLUSION: Malnutrition may play a significant role in the impairment of
      gastric acid and pancreatic secretion in Crohn's disease patients.

PMID- 15472525
TI  - Pharmacokinetics of mesalazine pellets in children with inflammatory bowel
      disease.
AB  - Mesalazine is a first-line drug in pediatric inflammatory bowel disease (IBD),
      and is customarily used to induce and maintain remission in mild to moderate
      disease. In children, pharmacokinetic data are scarce, and dosage recommendations
      are largely extrapolated from studies in adults. Aim of the study was to obtain
      the pharmacokinetic profile of a new mesalazine pellet formulation in children
      with ulcerative colitis and Crohn's colitis. A single oral dose of 20 mg/kg
      mesalazine was administered to 13 patients (age 6-16 years). Serial blood and
      urine sampling for determination of mesalazine and acetylmesalazine was performed
      before and during 24 hours following ingestion. Maximum plasma concentration of
      mesalazine (Cmax) was 1332 ng/mL (geometric mean, geometric coefficient of
      variation [CV]: 0.57), obtained 3.7 hours (tmax; CV: 0.31) after drug
      administration. Systemic exposure as determined by area under the plasma
      concentration-time curve (AUC(0-infinity) ) was 8712 ng/ml*h (CV: 0.44). Terminal
      half-life of elimination of mesalazine was 3.5 hours (t(1/2); CV: 1.43). This
      study presents extensive pharmacokinetic data on mesalazine in children with mild
      moderately active ulcerative colitis and Crohn's colitis. In comparison with
      previous experience in adults, pharmacokinetics of mesalazine administered as
      pellets appear to be similar in both populations.

PMID- 15472526
TI  - Comparison of a disease activity index and patients' self-reported symptom
      severity in ulcerative colitis.
AB  - BACKGROUND: A self-report instrument to measure disease activity in ulcerative
      colitis was compared with a full-scale measure of clinical and endoscopic
      activity, the St. Mark's index. We also tested the effects of symptom reporting
      style on both instruments. METHODS: Disease activity was measured in 94 patients
      with ulcerative colitis using the St. Mark's index and an instrument consisting
      of 7 self-reported symptoms. Reporting style was measured as health anxiety,
      measured with the Illness Behavior Questionnaire, and repressive coping, defined
      by scores on the Marlow-Crowne questionnaire and the State Anxiety Index.
      RESULTS: The St. Mark's index and the self-report index were highly correlated (R
      = 0.98, P < .001). Compared with the St. Mark's index, the self-report index
      categorized patients into inactive or active disease with a positive predictive
      value of 100% and negative predictive value of 100%. Reporting style was
      associated with differences in disease activity in both disease severity scales.
      CONCLUSIONS: A self-report measurement of ulcerative colitis disease activity is
      a valid alternative to complete clinical and endoscopic examination in subjects
      who do not have severe illness. Determination of disease severity in ulcerative
      colitis is vulnerable to individual biases in symptom reporting style, not only
      in self-report instruments, but also in an index that includes endoscopy and
      physical examination.

PMID- 15472527
TI  - Assessing the demand for psychological care in chronic diseases: development and
      validation of a questionnaire based on the example of inflammatory bowel disease.
AB  - BACKGROUND: This study was designed to develop and validate the ADAPT (Assessment
      of the Demand for Additional Psychological Treatment), a questionnaire assessing
      the demand for disease-oriented counseling (DOC), integrated psychosomatic care
      (IPC), and psychotherapy (PT) in chronically ill patients on the example of
      inflammatory bowel diseases (IBDs). METHODS: After its development, the ADAPT was
      distributed to 39 IBD patients along with the Hospital Anxiety and Depression
      scale (HAD), the Rating Form of IBD Patient Concerns (RFIPC), and a questionnaire
      on social support (SOZU-K22). For construct validity, 19 hypotheses were made on
      how DOC, IPC, and PT should correlate with HAD, RFIPC, SOZU-K22, and disease
      related variables. To analyze interindividual responsiveness, patients were
      classified according to their bio-psycho-social state, and DOC, IPC, and PT
      scores were compared between these classes. The test-retest method with a 4-week
      time lapse was used to analyze reliability and intraindividual responsiveness.
      DOC, IPC, and PT scores between baseline and follow-up were compared separately
      for patients classified as "stable" or "changed" according to changes in HAD and
      disease activity. RESULTS: Observed correlations were largely in agreement with
      the 19 hypotheses. DOC, IPC, and PT achieved significantly different scores
      between different patients. After 4 weeks, DOC, IPC, and PT revealed stable
      scores in patients with "stable" HAD and revealed significantly different scores
      in patients with "changed" HAD. Changed disease activity was not associated with
      significant changes of the ADAPT. CONCLUSIONS: The ADAPT is the first
      questionnaire to assess subjective demand for additional psychological care in
      chronically ill patients. The first application of the ADAPT to 39 IBD patients
      suggests its validity, reliability, and responsiveness.

PMID- 15472528
TI  - The epidemiology and phenotype of Crohn's disease in the Chinese population.
AB  - BACKGROUND: Inflammatory bowel disease is uncommon in Southeast Asia but is
      increasing in incidence. The epidemiology and phenotype of Crohn disease (CD) in
      the Chinese population is not well-known. The purpose of this study was to
      determine the incidence, temporal trend, clinical features, risk factors,
      extraintestinal manifestations, and the treatment of CD in the Chinese population
      of Hong Kong. METHODS: We performed a single-center study of consecutive definite
      CD cases based on internationally accepted criteria, with strict exclusion of
      infective enterocolitis. RESULTS: Eighty Chinese CD patients were recruited,
      characterized by male gender predominance (male:female ratio 2.5:1), no
      association with ever smoking (OR 1.02, 95% CI: 0.54-1.92), absence of familial
      clustering (0%), high proportion of upper gastrointestinal tract disease proximal
      to the terminal ileum (19%), and a low proportion of isolated terminal ileal
      disease (4%). The mean age at diagnosis was 33 years. Forty-five percent of
      patients had penetrating disease, 18% stricturing disease, and 37% had
      nonstricturing, nonpenetrating disease. Twenty-five percent of patients had at
      least 1 extraintestinal manifestation, and there was a high rate of ankylosing
      spondylitis (9%). The incidence of CD was 1.0 per 100,000 and has increased by 3
      fold during the past decade. The age-adjusted incidence was 3.0 per 100,000 (95%
      CI: 2.3-3.7 per 100,000). CONCLUSIONS: The incidence of CD in the Chinese is
      increasing. There are some notable epidemiological and phenotypic differences
      between Chinese CD with Caucasian CD including the lack of familial clustering,
      male predominance, and higher proportion of upper GIT involvement and lower
      frequency of isolated terminal ileal disease.

PMID- 15472529
TI  - Acute sinusoidal obstruction syndrome after 6-thioguanine therapy for Crohn's
      disease.
AB  - 6-Thioguanine (6-TG), the active metabolite of 6-mercaptopurine and its prodrug
      azathioprine, are thought to be responsible for clinical efficacy in the
      treatment of active Crohn's disease. Its use as a therapeutic agent for
      inflammatory bowel disease (IBD) has been limited to patients who are resistant
      to or intolerant of other antimetabolites. Short-term experience with this agent
      has not demonstrated an increased incidence of hematologic or hepatic toxicity;
      however long-term safety data are scarce. We herein report a patient who
      developed acute sinusoidal obstruction syndrome after 14 months of successful
      thioguanine treatment. This is the first report of such a complication in an
      adult treated with 6-TG for active Crohn's disease.

PMID- 15472530
TI  - Fatal staphylococcal sepsis in Crohn's disease after infliximab.
AB  - We report a case of a 40-year-old woman who had received infliximab for perianal
      Crohn's disease. After six infusions of infliximab, the patient developed
      staphylococcal pneumonia resulting in fatal adult respiratory distress syndrome.
      The case is discussed in the context of the toxicity profile of infliximab.

PMID- 15472531
TI  - Pneumocystis carinii pneumonia during maintenance anti-tumor necrosis factor
      alpha therapy with infliximab for Crohn's disease.
AB  - BACKGROUND: Clinical trials using infliximab have not reported cases of
      Pneumocystis carinii pneumonia (PCP), and PCP infection during standard medical
      treatment of inflammatory bowel disease is uncommon. Postmarketing surveillance
      through June of 2001 has identified 10 cases of PCP occurring during treatment
      with infliximab; 3 patients died. CASE HISTORY: A 19-year-old man with Crohn's
      colitis developed thrush, leukopenia, fever, shortness of breath, and dry cough
      21 months after initiating maintenance therapy with azathioprine and infliximab.
      Azathioprine had been at a stable dose of 75 mg per day (1 mg/kg) and the patient
      had received his 14th infusion of infliximab 4 weeks prior to presentation.
      Evaluation revealed the presence of Pneumocystis carinii on induced sputum.
      Azathioprine was discontinued, and the patient improved after initiating
      treatment with steroids and trimethoprim-sulfamethoxazole. Follow-up 2 weeks
      later confirmed clinical response to therapy. CONCLUSIONS: This case report
      describes the uncommon occurrence of Pneumocystis pneumonia in the setting of
      maintenance therapy for Crohn's disease using infliximab and azathioprine.
      Mechanisms by which azathioprine and infliximab may impair the natural defense
      mechanisms against Pneumocystis are discussed.

PMID- 15472532
TI  - C-reactive protein as a marker for inflammatory bowel disease.
AB  - The production of CRP occurs almost exclusively in the liver by the hepatocytes
      as part of the acute phase response upon stimulation by IL-6, TNF-alphaand IL-1
      betaoriginating at the site of inflammation. Its short half-life makes CRP a
      valuable marker to detect and follow up disease activity in Crohn's disease (CD).
      In contrast, ulcerative colitis has only a modest to absent CRP response despite
      active inflammation, and the reason for this is unknown. In CD, serum levels of
      CRP correlate well with disease activity and with other markers of inflammation
      as the CDAI, serum amyloid, IL-6 and faecal calprotectin. CRP is a valuable
      marker for predicting the outcome of certain diseases as coronary heart disease
      and haematological malignancies. An increased CRP (>45 mg/L) in patients with IBD
      predicts with a high certainty the need for colectomy and this by reflecting
      severe ongoing and uncontrollable inflammation in the gut. Finally, trials with
      anti-TNF and anti-adhesion molecules have shown that a high CRP predicts better
      response to these drugs. However, whether we need to include CRP as an inclusion
      criterion for future trials with biologicals is still a matter of debate.

PMID- 15472533
TI  - Regulatory T cells: peace keepers in the gut.
AB  - The mucosa-associated lymphoid tissue (MALT) has the task of protecting the host
      from pathogens while maintaining the integrity of the gut. Immune responses are
      tightly regulated such that there is tolerance of nonpathogenic bacteria as well
      as dietary antigens present in the intestinal lumen. The failure to control these
      responses leads to a disruption in tolerance, which has been proposed as one
      mechanism involved in the development of inflammatory bowel disease (IBD).
      Different mechanisms are involved in the control of immune responses in the
      intestinal tract, including active suppression by regulatory T cells. Distinct
      subsets of regulatory T cells coexist in the intestinal mucosa, which is a
      fertile environment for their growth. Most of these are defined by their
      phenotype and/or their ability to produce regulatory cytokines such as
      interleukin-10 and transforming growth factor-beta A lack of activation and/or
      expansion of regulatory cells could play a role in the uncontrolled inflammation
      seen in IBD. Regulatory T cells may be activated by cytokines, and their
      inductive phase may be antigen-driven. There are limited data relating to the
      true surface interactions regulating the activation of these cells. Most of the
      CD4 regulatory T cells (Tr1, Th3, and CD4 CD25+) are thought to interact with
      dendritic cells. Subsets of regulatory T cells (such as CD8 TrE cells) may
      recognize antigens presented by intestinal epithelial cells. A better
      understanding of the mechanisms by which these regulatory T cells are expanded
      and/or activated in the intestinal mucosa may provide clues as how to use them as
      a novel therapeutic tool in the treatment of patients with IBD.

PMID- 15472534
TI  - Guidelines for immunizations in patients with inflammatory bowel disease.
AB  - During the past 2 decades, medical therapy for Crohn's disease (CD) and
      ulcerative colitis (UC) has grown to incorporate a variety of immunesuppressing
      agents. At the same time, basic insights into the aberrant mucosal immune
      response underlying inflammatory bowel disease (IBD) have expanded dramatically.
      The interplay of host susceptibility to infection and the safety and efficacy of
      immunization for vaccine-preventable diseases has been explored in other immune
      mediated disease states but only rarely in IBD. The purpose of this review is to
      formulate best-practice recommendations for immunization in children and adults
      with IBD by considering the effects of the IBD disease state and its treatments
      on both the safety and efficacy of immunization. To do so, we first considered
      the routine recommendations for immunization of children, adults and distinct
      populations at increased risk for vaccine-preventable disease. Because it was
      rarely possible to examine direct data on safety and efficacy of immunization in
      IBD populations, we relied to a large extent upon extrapolation from similar
      populations and from knowledge of basic mechanisms. The literature suggests that
      efficacy of immunization may be diminished in some patients whose immune status
      is compromised by immune suppression. However, except for live agent vaccines,
      most immunizations may be safely administered to patients with IBD even when
      immune compromised. Conversely, protection against vaccine-preventable illness
      may be of even greater benefit to those at risk for morbid or lethal
      complications of infections because of an immune compromised state. We conclude
      that for most patients with IBD, recommendations for immunization do not deviate
      from recommended schedules for the general population.

PMID- 15472535
TI  - You say goodbye and I say aloe.

PMID- 15472536
TI  - "Is foe your friend?".

PMID- 15472537
TI  - Chromoendoscopy: an evolving standard in surveillance for ulcerative colitis.

PMID- 15472538
TI  - To (I)B(D) or NOD2 (I)B(D)--are paneth cells the answer?

PMID- 15472539
TI  - Crohn's disease, infliximab and idiopathic thrombocytopenic purpura.

PMID- 15472540
TI  - Hypersensitivity reaction to azathioprine in a patient with ulcerative colitis.
      Infrequent manifestations.

PMID- 15472541
TI  - Infliximab therapy in a patient with Crohn's disease and chronic hepatitis B
      virus infection.

PMID- 15472542
TI  - Crohn disease versus systemic lupus erythematosus: an autopsy diagnosis of
      predominantly extraintestinal Crohn disease.

PMID- 15472543
TI  - Application of a new collagen-based sealant for the treatment of pancreatic
      injury.
AB  - Pancreatic injury is the most frequent serious morbidity that can occur following
      laparoscopic splenectomy. The presumed mechanism of injury is direct trauma to
      the pancreatic tail during hilar dissection or transection with endovascular
      staplers. It was our aim to study the direct application of topical sealants to a
      pancreatic injury to prevent a pancreatic leak. A porcine model of pancreatic
      injury in a normal pancreas was developed. Fourteen animals underwent midline
      laparotomy and subtotal (8 cm) distal pancreatectomy. The pancreas was sharply
      divided and minimal cauterization used. A (1/4)-inch round Jackson Pratt drain
      was secured to the pancreatic stump in all animals. The control group (n = 7)
      underwent no further treatment. Two groups underwent treatment with a sealant.
      Group 1 (n = 3) had a hydrogel applied to the pancreatic remnant. Group 2 (n = 4)
      had a biodegradable sealant of PEG (polyethylene glycol)-collagen formulation
      applied to the pancreatic stump by aerosol. During the postoperative period,
      animals were fed 2.2 lb/d of a high fat (10% lard) diet to stimulate pancreatic
      exocrine function. Total daily drain outputs were recorded, and drain amylase
      content and serum amylase concentration were measured on postoperative days 3, 7,
      and 10. A significant pancreatic leak was defined as a drain to serum amylase
      content of greater than 3:1. Animals were killed on day 10 and explored for
      undrained fluid collections. The pancreas was removed for histologic evaluation.
      Control and treatment groups were compared using repeated measures ANOVA of log
      transformed data. All animals survived until elective necropsy. In group 1,
      average total drain outputs were not significantly less than the controls (125 mL
      versus 269; P = .66). The mean drain/serum amylase concentration on days 3, 7,
      and 10 were not significantly different between group 1 and the control group.
      Group 2 had significantly less overall average drainage output than controls (40
      mL versus 269 mL; P = .0006). Furthermore, group 2 had a significant reduction in
      pancreatic leaks on days 3, 7, and 10 as measured by mean drain/serum amylase
      concentration. No undrained fluid collections were identified at autopsy. Based
      on our experimental porcine model, a novel collagen-based, biodegradable hydrogel
      can prevent a ductal leak following pancreatic injury. These encouraging data
      have fostered application by aerosol treatment to the hilar bed at laparoscopic
      splenectomy to diminish capsular disruption from mechanical injury.

PMID- 15472544
TI  - Laparoscopic radiofrequency ablation of liver tumors combined with colorectal
      procedures.
AB  - Laparoscopic radiofrequency ablation (RFA) is gaining increasing acceptance as a
      treatment option for primary and secondary liver tumors with minimal morbidity.
      The purpose of this study is to see if adding a colorectal procedure to RFA
      increases the risk of hepatic abscess. Of the 310 patients with 1,080 primary and
      secondary liver tumors undergoing laparoscopic radiofrequency ablation (RFA), 16
      patients underwent RFA in combination with various colorectal procedures. Data
      were collected prospectively. The concomitant procedures included loop ileostomy
      closures in 6 patients; laparoscopic-assisted right hemicolectomy in 3 patients;
      laparoscopic-assisted anterior resection in 2 patients; and open transverse
      colectomy, open anterior resection, open low anterior resection, open loop
      transverse colostomy formation, and anal stricture dilatation in 1 patient each.
      Mean +/- SD hospital stay was 2.9 +/- 1.7 days. There was no mortality, and the
      only complication was the development of a right flank abscess after laparoscopic
      assisted right hemicolectomy that was treated with percutaneous drainage.
      Although patients undergoing laparoscopic RFA in combination with a clean
      contaminated procedure could be at high risk for secondary infection of ablated
      foci, this was not observed. This approach is safe and does not impair recovery
      from either procedure. These data support the concept that RFA may be safely used
      with concomitant colon resections to treat liver metastases that may be
      resectable but are associated with increased morbidity if resected synchronously.

PMID- 15472545
TI  - Laparoscopic "second-look" in the management of mesenteric ischemia.
AB  - Mesenteric ischemia is a major cause of mortality in surgery. Despite the
      advances in medicine, considerable number of patients undergoes reoperations for
      a better assessment of intestinal viability. Although great majority of these
      second-look operations are "negative explorations," progressive nature of this
      devastating disease pushes surgeons to re-explore the abdomen. This study
      compares open and laparoscopic "second-look" procedures in patients with
      mesenteric ischemia. In the first group (n = 41), abdomen was closed and second
      look laparotomy was performed to 23 patients. In the second group (n = 36), a 10
      mm trocar was inserted before closing the abdomen and second-look intervention
      was performed by a telescope to 23 patients. Sixteen of relaparotomies in the
      first group (70%) revealed nothing and were unnecessary. Two patients (8%) in the
      laparoscopy group needed re-resection while 20 patients (87%) were rescued from
      unnecessary laparotomies. Conclusively, patients with mesenteric ischemia are
      "ill enough" to deserve the "minimal invasion" spirit of laparoscopic surgery.

PMID- 15472546
TI  - Early outcomes of laparoscopic procedures performed on military personnel with
      total rectal prolapse and follow-up.
AB  - Total rectal prolapse is a disorder frequently associated with constipation and
      anal incontinence. The aim of this study was to evaluate the outcomes of the
      complications, pain management, hospital stay, constipation, and anal functions
      of the patients undergoing 2 types of laparoscopic surgical approaches. In this
      study, 33 patients underwent either laparoscopic rectopexy or hand-assisted
      laparoscopic resection rectopexy. Preoperative colonic transit time, defecation,
      postoperative pain scoring, pre-postoperative evaluation of the anal function,
      and the changes in constipation and relating symptoms were assessed.
      Postoperative evaluation had been performed at the sixth week and the twelfth
      month. Median operation time was 137 minutes for rectopexy and 230 minutes for
      resection rectopexy group. Median postoperative hospital stay was 3 days for
      patients with rectopexy and 7 days for patients with resection rectopexy.
      Patients needed painkillers in short postoperative period for pain management in
      both groups. Continence was improved in 11 of 13 patients (84.6%) in a year after
      laparoscopic surgery. In 15 patients (45.5%), preoperative constipation either
      remained in the same or became worse in 7 (21.1%) in a year after surgery. No
      patient developed recurrence in the median follow-up period, which was about 15
      months. Laparoscopic rectopexy and resection rectopexy in the young aged patients
      working the Army are carried out with less morbidity rate. We eliminated the
      total prolapse and cure incontinence in almost all patients. In addition to
      constipation was reduced by laparoscopic surgical approaches in a short time
      hospitalization with short time painkiller need.

PMID- 15472547
TI  - No clip, no ligature laparoscopic appendectomy.
AB  - Laparoscopic appendectomy (LA) is one of the common procedures being carried out
      in general surgery. The technique of bipolar coagulation (BC) has been
      effectively employed in obstetric and gynecologic procedures but has not been
      used for intestines. We present the technique of LA using BC at our center. The
      technique consisted of identifying the appendix and coagulating the appendicular
      stump with bipolar coagulation until there were no bubbles at the cautery site,
      and a constriction ring formed at the site of coagulation. Sixty patients with
      acute or recurrent appendicitis underwent the procedure. The median duration of
      BC was 90 seconds. The median duration of surgery was 25 minutes, postoperative
      hospital stay was 3 days, and time to oral feeds was 12 hours. The technique of
      laparoscopic appendectomy by bipolar coagulation is very simple and economical.
      The duration of surgery is less than for the standard technique of laparoscopic
      appendectomy; no clip applicators, needle holders or knot pushers are required,
      and no foreign materials like ligatures or clips are needed.

PMID- 15472548
TI  - Extraperitoneal laparoscopic approach to Spigelian hernia combined with groin
      hernias.
AB  - Spigelian hernia is a rare form of abdominal wall hernia. It occurs when
      peritoneum with or without organs or preperitoneal fat exists through a defect in
      the Spigelian fascia. A 63 year old male patient complaint of inguinal hernias
      and Spigelian hernia treated with laparoscopic approach that has been not
      previously reported in the literature. The use of the laparoscope has simplified
      the diagnosis, clarified its localization, and facilitated the subsequent repair
      of these hernias.

PMID- 15472549
TI  - The feasibility of adopting laparoscopic incisional hernia repair in general
      surgery practice: early outcomes in an unselected series of patients.
AB  - A laparoscopic approach to incisional hernia repair has been shown to be safe and
      effective in selected patients. We report our early outcomes following
      laparoscopic ventral/incisional hernia repair (LVHR) in an unselected series of
      patients encountered in general surgery practice. All patients referred with
      incisional hernia were offered a laparoscopic repair using prosthetic mesh.
      Patients were not excluded from laparoscopic approach on the basis of age,
      previous surgery, defect size, intraperitoneal mesh, body mass index (BMI),
      comorbidities, or abdominal wall stomas. We followed 28 consecutive patients who
      underwent LVHR (17 primary, 11 recurrent hernias). Laparoscopic repair was
      completed in 27 patients with a mean operative time of 141.6 +/- 11.9 minutes.
      There were no intraoperative complications. The mean size of the abdominal wall
      defects was 153.4 +/- 27.5 cm and the mean mesh size was 349.2 +/- 59.1 cm. The
      mean hospital stay was 3.7 +/- 0.3 days. Nine patients developed large wound
      seromas; all spontaneously resolved. Our experience suggests that LVHR is
      feasible as a primary approach to most incisional hernias encountered in general
      surgery practice.

PMID- 15472550
TI  - Inguinodynia after two inguinal herniorrhaphy methods.
AB  - The aim of this study was to compare the rate and characteristics of
      postoperative neuralgia after 2 methods of inguinal hernia repairs. Between July
      1997 and December 2000, 400 inguinal hernia repairs were performed and followed
      up in a prospective trial about postoperative nerve irritations: 200 patients
      with laparoscopic transabdominal hernioplasty (TAPP group), and 200 patients with
      tension-free hernia repair using Lichtenstein's technique (LICH group). We
      applied a clinic protocol of data about pain location, neuralgia characteristics,
      and period of time until the patient was completely pain free. The global rate of
      nerve irritation in the study was 7.6% (30 cases); in the TAPP group, it was 5.5%
      (n = 11) and in the LICH group, it was 9.5% (n = 19) (P = .03). The genitofemoral
      nerve was affected with particularly high frequency (4.3% in the global series);
      although in laparoscopic repair, the lateral cutaneous nerve of the thigh (LFC)
      was most damaged (3.3% in TAPP group). We observed more persistent symptoms in
      LICH group, while in TAPP group the most of cases was transitory (P = .08). There
      were no significant differences in pain characteristics according to clinical
      type of hernia. The TAPP method causes less rate of postoperative inguinal
      neuralgia than Lichtenstein repair, emphasizing more persistent discomfort in
      anterior approach than laparoscopic repair.

PMID- 15472551
TI  - Totally extraperitoneal endoscopic (TEP) treatment of sportsman's hernia.
AB  - Sportsman's hernia is a term used to describe a weakness or disruption of is a
      term used to describe the musculotendinous part of the posterior inguinal wall,
      which causes persistent groin pain in athletes. A video-assisted placement of
      extraperitoneal synthetic mesh to support the damaged area may heal this injury.
      Forty-one male athletes at an elite level (mean age 27 +/- 7.1 years) with
      chronic groin pain, which was resistant to conservative therapy, were referred to
      surgery by sports clinics or club doctors. The majority of the patients were
      soccer (58%) or ice hockey players (27%) at a professional level. A 10 x 15 cm
      polypropylene mesh was placed into the preperitoneal space using a totally
      extraperitoneal video-assisted technique. The severity of pain, and the time to
      return to sports, were determined after 1 month and after the mean follow-up of 4
      years. On operation, no macroscopic abnormality was found in 24 patients (58%),
      obvious musculotendinous tear was present in 10 patients, and muscle asymmetry
      was present in 7 patients. All except 2 patients (95%) returned to their sport
      activities after 1 month of convalescence. No immediate or long-term
      complications were associated with the operation. The placement of a retropubic
      mesh was safe and a mini-invasive method to repair sportsman's hernia and chronic
      groin pain of athletes.

PMID- 15472552
TI  - Patients' perception of open and endoscopic extraperitoneal inguinal
      hernioplasty.
AB  - Most hernia studies have focused on the assessment of clinical outcomes. Few have
      examined patients' perception of the operative procedures. The present study was
      undertaken to evaluate the patients' preferred method of repair in those who had
      personal experience of both endoscopic totally extraperitoneal inguinal
      hernioplasty (TEP) and open inguinal hernia repair. Qualitative analysis of their
      choice of method was also examined. Between June 1999 and February 2003, a
      prospective survey was conducted on 590 patients who underwent TEP at our
      institution. Previous experience of open inguinal hernia repair was a
      prerequisite for entry into the study. Patients were interviewed during the first
      postoperative follow-up to document their preference of TEP or open repair in the
      event of future recurrence or development of a contralateral inguinal hernia. A
      total of 121 patients were recruited into the study. Of these, 102 (84.3%) and 11
      (9.1%) patients opted for future TEP and open repair respectively. Documented
      reasons supporting their choice of TEP included less postoperative pain (n = 69),
      faster recovery (n = 25), shorter incisions (n = 8), early ambulation (n = 5),
      and others (n = 11). Eight (6.6%) patients had no particular preference. More
      than 80% of patients, who had experience of TEP and open repair, preferred to
      undergo TEP. Patients presenting with primary inguinal hernia should be given the
      options of TEP and open mesh hernioplasty with detailed explanation of advantages
      and drawbacks of each procedure. Individual preference for the type of surgery
      should be considered in the management plan of each patient.

PMID- 15472553
TI  - Role of different techniques for the placement of Denver peritoneovenous shunt
      (PVS) in malignant ascites.
AB  - The aim of the study is to evaluate 3 different techniques of Denver
      peritoneovenous shunt (PVS) placement. Fifty-three patients with malignant
      ascites underwent placement of 55 Denver PVS by a surgical (33 cases) or
      percutaneous (18) or laparoscopically assisted (4) procedure. There were 2 cases
      of postoperative mortality due to cardiac failure, and 7 cases of shunt
      obstruction (2 of them required replacement). Twenty patients underwent
      subsequent palliative treatment with chemotherapy or surgery. Complication and
      control of ascites rates are similar for the 3 techniques. Placement of Denver
      PVS for the treatment of malignant ascites appears to be a safe and useful
      procedure. Surgical dissection of the jugular vein is not mandatory. The
      percutaneous technique is the easiest, fastest, and least invasive procedure.
      Laparoscopic-assisted positioning is recommended if a peritoneal biopsy and/or
      abdominal exploration is required for a definitive diagnosis.

PMID- 15472554
TI  - Reversed 5 pattern of diagnostic laparoscopy during laparoscopic cholecystectomy
      and its standardization.
AB  - An attempt at standardization of the diagnostic laparoscopy (DL) procedure during
      laparoscopic cholecystectomy (LC) was undertaken by establishing a simple pattern
      and checking its applicability in 100 consecutive LCs. DL was performed following
      the reversed number 5 pattern, starting from the right upper quadrant and moving
      to the left upper quadrant, left flank, back to the right flank along the
      transverse colon, down to the pelvis, along the sigmoid to the left flank, and
      back to the right upper quadrant inspecting small bowel. DL was incomplete in 11
      patients. Inspection lasted 6-12 minutes (operation time increase, 14%).
      Abnormalities were discovered in 38% of patients, diagnosis elucidated in 8%,
      intervention undertaken in 11%, and control or further treatment proposed in 33%,
      without morbidity and mortality. The reversed 5 pattern of diagnostic laparoscopy
      is feasible and safe. It can be routinely done during LC in the general hospital
      setting. Standardization of diagnostic laparoscopy during laparoscopic
      cholecystectomy seems necessary for early disclosure of visible disorders and for
      medicolegal purposes.

PMID- 15472555
TI  - Peroral and transgastric esophageal anastomosis with flexible shaft remote
      control stapler (SurgASSIST).
AB  - Stapled cervical esophageal anastomoses are technically challenging and are
      associated with relatively high complication rates, particularly in leaks and
      anastomotic strictures. We describe the use of a flexible shaft, remote-control,
      circular stapling device in forming high esophageal anastomoses in 2 patients.
      Retrograde transgastric and prograde peroral approaches are evaluated comparing
      ease of technical application and outcomes. Both procedures were performed after
      total esophagectomy for cancer in a 72-year-old male patient with preoperative
      down-staging and a 78-year-old female who proceeded directly to surgery. The
      introduction of rigid staplers in the esophagus by either route can be difficult
      and technical pointers and the potential applications of the flexible SurgASSIST
      device are discussed. Potential benefits include shorter time for constructing
      the anastomosis and a wider lumen resulting in possible cost benefit. Both
      patients had uneventful technical construction of stapled anastomoses, and the
      only complication in the female was a leak in the gastric close-off at the site
      of introduction of the flexshaft. Both are alive and well without recurrence at 2
      years and 22 months.

PMID- 15472556
TI  - Laparoscopic removal of an intragastric foreign body with endoscopic assistance.
AB  - We report the successful laparoscopic removal of an intragastric foreign body. A
      57-year-old woman who had accidentally swallowed her own partial denture was
      referred to our hospital for its removal. Laparoscopic removal of the foreign
      body was urgently performed with the assistance of oral endoscope, following an
      earlier failed endoscopic removal associated with subcutaneous and mediastinal
      emphysema. The foreign body was removed from the stomach through a gastrotomy.
      There were no perioperative complications. The patient was uneventfully
      discharged on the ninth postoperative day. Laparoscopic removal of an
      intragastric foreign body is a feasible and safe treatment, and can be an
      alternative choice following failed endoscopic removal.

PMID- 15472557
TI  - A novel laparoscopic technique for removal of foreign bodies from the urinary
      bladder using carbon dioxide insufflation.
AB  - We describe a new technique for extraction of complex foreign bodies from the
      urinary bladder which cannot be removed through the conventional pediatric
      cystoscope, thereby avoiding an open cystotomy and the morbidity associated with
      it. Using cystoscopy as the optical device through the urethra, a 10-mm
      laparoscopic port can be introduced suprapubically under vision for extraction of
      complex foreign bodies while the bladder remains insufflated with carbon dioxide
      at a pressure of 12 mm mercury.

PMID- 15472558
TI  - Pathogenesis of acute cholecystitis and recurrent pyogenic cholangitis.

PMID- 15472563
TI  - A staged protocol for soft tissue management in the treatment of complex pilon
      fractures.
AB  - OBJECTIVE: To determine whether open reduction and internal fixation of intra
      articular pilon fractures using a staged treatment protocol results in minimal
      surgical wound complications. DESIGN: Retrospective. SETTING: Level 1 trauma
      center. PATIENTS/PARTICIPANTS: Between January 1991 and December 1996, 226 pilon
      fractures (AO types 43A-C) were treated, of which 108 were AO type 43C. Fifty-six
      fractures were included in a retrospective analysis of a treatment protocol.
      Injuries were divided into Group 1, thirty-four closed fractures, and Group II,
      twenty-two open fractures (three Gustilo Type 1, six Type II, eight Type IIIA,
      five Type IIIB). METHODS: The protocol consisted of immediate (within twenty-four
      hour) open reduction and internal fixation of the fibula when fractured, using a
      one-third tubular or 3.5-millimeter dynamic compression plate and application of
      an external fixator spanning the ankle joint. Patients with isolated injuries
      were discharged after initial stabilization and readmitted for the definitive
      reconstruction. Polytrauma patients remained hospitalized and were observed.
      Formal open reconstruction of the articular surface by plating was performed when
      soft tissue swelling had subsided. Complications were defined as wound problems
      requiring hospitalization. All affected limbs were then evaluated via chart and
      radiograph review, patient interviews, and physical examination until surgical
      wound healing was complete, for a minimum of twelve months. RESULTS: Group I
      (closed pilon): Follow-up was possible in twenty-nine out of thirty fractures (97
      percent). Average time from external fixation to open reduction was 12.7 days.
      All wounds healed. None exhibited wound dehiscence or full thickness tissue
      necrosis requiring secondary soft tissue coverage postoperatively. Seventeen
      percent (five out of twenty-nine patients) had partial-thickness skin necrosis.
      All were treated with local wound care and oral antibiotics and healed
      uneventfully. There was one late complication (3.4 percent), a chronic draining
      sinus secondary to osteomyelitis, which resolved after fracture healing and metal
      removal. Group II (open pilon): Follow-up was possible in seventeen patients with
      nineteen fractures (86 percent). Average time from external fixation to formal
      reconstruction was fourteen days (range 4 to 31 days). By definition, all Gustilo
      Type IIIB fractures required flap coverage for the injury. Two patients
      experienced partial-thickness wound necrosis. These were treated with local wound
      care and antibiotics. All surgical wounds healed. There were two complications
      (10.5 percent), both deep infections. One Type I open fracture developed wound
      dehiscence and osteomyelitis requiring multiple debridements, intravenous
      antibiotics, subsequent removal of hardware, and re-application of external
      fixator to cure the infection. One Type IIIA open fracture of the distal tibia
      and calcaneus developed osteomyelitis and required a below-knee amputation.
      CONCLUSION: Based on our data, it appears that the historically high rates of
      infection associated with open reduction and internal fixation of pilon fractures
      may be due to attempts at immediate fixation through swollen, compromised soft
      tissues. When a staged procedure is performed with initial restoration of fibula
      length and tibial external fixation, soft tissue stabilization is possible. Once
      soft tissue swelling has significantly diminished, anatomic reduction and
      internal fixation can then be performed semi-electively with only minimal wound
      problems. This is evidenced by the lack of skin grafts, rotation flaps, or free
      tissue transfers in our series. This technique appears to be effective in closed
      and open fractures alike.

PMID- 15472564
TI  - Percutaneous pin placement in the medial calcaneus: is anywhere safe?
AB  - OBJECTIVE: To redefine the medical calcaneal anatomic safe zone for pin placement
      with respect to reproducible palpable landmarks. DESIGN: Anatomic study. SETTING:
      Medical school anatomy laboratory. INTERVENTIONS: Thirty-three fresh-frozen adult
      cadaveric feet were used. Three palpable anatomic landmarks were identified on
      each ankle and labeled as Point A (posteroinferior medial calcaneus), Point B
      (inferior medial malleolus), and Point C (navicular tuberosity). The medial
      neurovascular bundle was carefully dissected, and the medial calcaneal nerve, the
      most posterior branch of the lateral plantar nerve, the lateral plantar nerve,
      the medial plantar nerve, and the posterior tibial artery were identified. These
      structures were recorded at the point at which they transected a line from Point
      A to B and from Point A to C. Based on the findings of the first thirty-three
      feet, two pins were placed percutaneously into the medial calcaneus of ten
      additional feet. Pin 1 was placed one half the distance from Point A to B. Pin 2
      was placed one third the distance from Point A to C. The neurovascular structures
      were then dissected and identified in relation to the pin position. RESULTS: The
      medial calcaneal, most posterior branch of the lateral plantar, and lateral
      plantar nerves are at significant risk for abutting the pins or being directly
      injured at the margins of these relative safe zones. CONCLUSION: The medial
      calcaneus provides a small window for safe percutaneous pin placement. Posterior
      to the halfway point from Point A to B and posterior to the one-third mark from
      Point A to C remain the relatively safest regions; a more posterior placement in
      the safe zone is safest. Careful blunt dissection and the use of cannulas may
      help to avoid neurovascular injury.

PMID- 15472565
TI  - Safe extracapsular placement of proximal tibia transfixation pins.
AB  - OBJECTIVE: To identify the anatomic detail of the knee joint capsular insertion
      site on the proximal tibia, specifically as it relates to transfixation pins.
      DESIGN: Identification of capsular anatomy by anatomical dissection of cadaveric
      specimens, with radiography and arthroscopy of patients. SETTING: Cadaveric
      dissection. OUTCOME MEASURES: Anatomic observation of the capsular attachment
      site in relation to the tibial articular surface. RESULTS: The capsule inserts
      four to fourteen millimeters below the articular surface in a regular pattern.
      The anterior half of the circumference is close to the joint line (less than six
      millimeters). Posteromedially and posterolaterally, there are extensions distally
      to fourteen millimeters, occasionally communicating with the tibiofibular joint.
      CONCLUSION: Transfixing wires and half-pins can be placed in the proximal tibia
      without capsular penetration if kept more than fourteen millimeters from the
      subchondral line. If wire placement closer to the joint is required, wires should
      be placed in Zone 1 (the anterior half) and at least six millimeters from
      subchondral bone to avoid capsular penetration.

PMID- 15472566
TI  - Evaluation of orthopaedic injuries in Operation Enduring Freedom.
AB  - Orthopaedic injuries constitute a majority of the combat casualties in recent
      U.S. military conflicts. Orthopaedic injuries sustained in Operation Enduring
      Freedom from December 2001 to January 2003 that were treated in forward-deployed
      military medial facilities and evacuated to a U.S. army medical center were
      reviewed. The spectrum of injuries included open fractures, amputations,
      neurovascular, and soft-tissue injuries. Forty-four patients (85%) received
      treatment beyond local wound care prior to arrival at a military medical center.
      Debridement and irrigation was the most commonly performed procedure due to the
      contaminated nature of these combat injuries. There were no infections among
      patients with open fractures, and no patients with external fixators had pin
      tract infections. None of the open fracture patients underwent primary internal
      fixation or primary wound closure. The average time from injury to wound coverage
      of the open fracture wounds was 12 days. Two amputations were infected and were
      treated with revision and delayed wound closure. There were no primary
      amputations done at our institution due to infection or ischemia. All arterial
      injuries underwent urgent revascularization in a field hospital. None of the
      arterial repairs required revision after evacuation to a medical center.
      Operation Enduring Freedom has been an excellent example of how early and
      aggressive intervention in a forward-deployed area has a significant effect on
      rehabilitative and reconstructive efforts at a rear echelon tertiary care center.

PMID- 15472567
TI  - Herrnstein's hyperbolic matching equation and behavioral pharmacology: review and
      critique.
AB  - Behavioral pharmacologists have enlisted Herrnstein's (1970) hyperbolic matching
      equation to understand the behavioral effects of drugs. Herrnstein's hyperbola
      describes the relation between absolute response rate and reinforcement rate. The
      equation has two fitted parameters. The parameter k represents the asymptotic
      response rate, and the parameter r(e) represents the reinforcement rate necessary
      to obtain half the asymptotic response rate. According to one interpretation of
      the equation, changes in k should reflect changes in response or motoric
      variables, and changes in r(e) should reflect changes in reinforcer or
      motivational variables, or changes in reinforcement from sources extraneous to
      the instrumental response. We review research that has applied Herrnstein's
      equation to distinguish the motoric from the motivational effects of drugs, and
      to identify additional independent variables responsible for drug effects, such
      as extraneous reinforcement. The validity of inferences about drug effects
      depends on the consistency of how k and r(e) respond to environmental
      manipulations: k should change only with response or motoric variables, and r(e)
      should change with reinforcer or motivational variables and with the rate of
      extraneous reinforcement. Empirical tests of these predictions, however, have
      produced inconsistent results. The review suggests that Herrnstein's theory has
      not fulfilled its promise of identifying the behavioral mechanisms of drug
      action. Modifications to the equation, known as bias and sensitivity, may explain
      some of these inconsistent results, and the modified equation may have utility in
      behavioral pharmacology.

PMID- 15472568
TI  - Behaviour-based assessment of the duration of laparotomy-induced abdominal pain
      and the analgesic effects of carprofen and buprenorphine in rats.
AB  - Prevention of unnecessary pain in laboratory animals requires reliable and
      practically useful tools for assessing pain severity and analgesic efficacy. We
      have used a behaviour-based pain scoring system to determine the duration of pain
      resulting from laparotomy, and the duration of analgesia afforded by orally
      administered (p.o.) buprenorphine and subcutaneously administered (s.c.)
      carprofen or buprenorphine in rats. One hour before laparotomy Fisher 344 rats
      received either saline as a control (0.2 ml/100 g s.c.), carprofen (5 mg/kg s.c.)
      or buprenorphine (0.05 mg/kg s.c. or 0.4 mg/kg p.o.). The rats were housed singly
      for 10-min periods of behaviour recording, beginning 30 min after completing
      surgery. Recording was repeated at three time points every 2 h. The behaviour of
      controls was distinct from that of the analgesic-treated animals throughout
      recording; however, the major signs of pain (back-arching, staggering and
      writhing) were prominent during only the first 270 min in the saline group. This
      was followed by a period of more subtle differences between the saline- and drug
      treated groups. It was concluded that the most acutely painful effects of surgery
      in this model lasted for between 270 and 390 min, and that this was alleviated
      throughout its duration by subcutaneously administered carprofen or
      buprenorphine, and also buprenorphine administered orally. The study demonstrates
      a clinically relevant and practically useful approach to assessing the duration
      of post-surgical abdominal pain and analgesic effects in rats.

PMID- 15472569
TI  - Involvement of nucleus accumbens in L-arginine-induced conditioned place
      preference in rats.
AB  - In the present study, the effects of intraperitoneal, intra-accumbal and intra
      ventral tegmental area administration of L-arginine and N(G)-nitro-L-arginine
      methyl-ester (L-NAME) on conditioned place preference behavior were studied.
      Intraperitoneal (i.p.; 0.5, 1 and 5 mg/kg) and intra-accumbal (intra-NAc; 0.3, 1
      and 3 microg/rat), but not intra-ventral tegmental area (intra-VTA; 0.3, 1 and 3
      microg/rat) administrations of L-arginine produced a significant place
      conditioning. Similar injections of L-NAME did not produce any response. However,
      intraperitoneal pretreatment of the animals with L-NAME (5, 10 and 20 mg/kg), 30
      min before L-arginine administration, significantly abolished the acquisition of
      place conditioning induced by either intraperitoneal or intra-accumbal injection
      of L-arginine. Moreover, injection of L-NAME (5, 10 and 20 mg/kg) on the test day
      did not alter the L-arginine response. The results may indicate that L-arginine
      induces conditioned place preference via an increase in nitric oxide (NO) in the
      nucleus accumbens.

PMID- 15472570
TI  - Cocaine-induced 'active immobility' and its modulation by the serotonin1A
      receptor.
AB  - 'Active immobility' (AI) is an independent behaviour that can be characterized by
      behavioural immobility, an increased muscular rigidity and the sustaining of an
      unusual posture. In previous studies with cocaine we observed, concomitant with
      hyperlocomotion and increased rearing activity, an increase in AI in well
      habituated animals, which may constitute another 'positive' acute effect of
      cocaine on behaviour. The contribution of the serotonergic (5-HT) system to AI is
      well established. However, little information exists about the contribution of
      particular 5-HT-receptor subtypes. In order to examine a possible role of the 5
      HT1A receptor on this effect of cocaine, we systematically re-analysed four
      previous experiments in well-habituated animals and one in little-habituated
      animals, focusing on the acute behavioural effects of cocaine on AI. We found
      that, in well-habituated animals, cocaine at a medium dose (10 mg/kg, i.p.)
      induces AI behaviour, which, however, does not correlate with cocaine effects on
      locomotion, rearing or grooming behaviour. However, there was no effect of
      cocaine (1, 5 or 15 mg/kg, i.p.) on AI in little-habituated animals. The 5-HT1A
      receptor antagonist, WAY 100635 [N-[2-(4-2-methoxyphenyl)-1-piperazinyl]ethyl]-N
      (2-pyridinyl) cyclohexane carboxamide trihydrochloride] (0.4 mg/kg, i.p.),
      potentiated cocaine-induced AI in well-habituated animals, while the 5-HT1A
      receptor agonist, 8-OH-DPAT (0.2 mg/kg, i.p.), attenuated it. The local
      application of 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] into the
      nucleus accumbens (0, 1, 10 micromol/l) or hippocampus (0, 0.1, 1, 10 micromol/l)
      modulated cocaine-induced AI in a complex way. These results showed that cocaine
      induces AI at a medium dose in well-habituated but not in little-habituated
      animals. The cocaine-induced AI in well-habituated animals can be potentiated by
      systemic 5-HT1A-receptor antagonism and attenuated by 5-HT1A-receptor agonism.
      Two experiments with local activation of postsynaptic 5-HT1A receptors revealed
      that both nucleus accumbens and hippocampal 5-HT1A-receptor populations are
      involved in the expression of cocaine-induced AI.

PMID- 15472571
TI  - Discriminative stimulus effects of ethanol: lack of interaction with taurine.
AB  - Recent microdialysis studies showed that ethanol administration increases the
      release of taurine in various rat brain regions, and it was suggested that this
      increase in extracellular concentrations of taurine might mediate some of the
      neurochemical effects of ethanol. Previous drug discrimination studies showed
      that positive modulators of the GABA(A) receptor consistently substituted for
      ethanol discriminative stimulus effects. Since taurine is also believed to
      modulate GABA(A) receptor activity, this study addressed the hypothesis that
      taurine mediates the discriminative stimulus effects of ethanol due to GABA(A)
      activation. Male Long-Evans rats were trained to discriminate water from either 1
      or 2 g/kg ethanol. In a first experiment, various taurine doses (0-500 mg/kg)
      were tested to investigate whether taurine substitutes for ethanol. In a second
      experiment, rats were pretreated with either 500 mg/kg taurine or an equivalent
      volume of saline before testing for ethanol discrimination with various ethanol
      doses (0-2.0 g/kg). The results showed that taurine does not substitute for
      ethanol at any tested doses. In addition, taurine pretreatments failed to modify
      the dose-response curve for ethanol discrimination. These results demonstrate
      that taurine is not directly involved in mediating the discriminative stimulus
      effects of ethanol. It is therefore very unlikely that the brain release of
      taurine observed after ethanol administration is implicated in the major
      pharmacological effects of ethanol, i.e. positive modulation of GABA(A) receptor,
      that mediate its discriminative stimulus effects.

PMID- 15472572
TI  - Low-dose diazepam primes motivation for alcohol and alcohol-related semantic
      networks in problem drinkers.
AB  - Considerable research with animals indicates that the GABA-benzodiazepine (BZ)
      system plays a key role in alcohol reinforcement. However, only limited research
      appears to have assessed this issue directly in humans. The present study
      investigated whether low-dose diazepam would cross-prime motivation for alcohol
      in problem drinkers. Twelve male problem drinkers (Alcohol Dependence Scale; ADS
      score > or =9) received oral diazepam (5 mg) and placebo, in a counterbalanced
      manner on separate sessions. There were three measures of primed motivation for
      alcohol: self-reported desire for alcohol, consumption of placebo beer in an
      ostensible taste test procedure, and automatically executed vocal reading
      responses to Alcohol versus Neutral words on a computer-based task. Diazepam
      significantly increased beer consumption, and produced a marginally significant
      increase in reported desire for alcohol. On the reading task, diazepam
      significantly decreased response latency to Alcohol words relative to Neutral
      words. Latency to Alcohol words correlated significantly with beer consumption
      under the drug. Moreover, response latency to Alcohol words under the drug also
      predicted ADS scores. Thus, severity of dependence was directly linked with
      vulnerability to a BZ priming effect on motivation for alcohol. These findings
      provide direct evidence that the GABA-BZ system plays an important role in
      alcohol reinforcement in problem drinkers.

PMID- 15472573
TI  - D-Amphetamine reinstates behavior previously maintained by food: importance of
      context.
AB  - The drug self-administration reinstatement procedure provides an important animal
      model of relapse. While the procedure is widely used, there has been little
      investigation of the basic processes involved. This experiment determined the
      specificity of reinstatement by examining reinstatement of food seeking by D
      amphetamine. During training, 24 rats pressed levers for food. Eight rats
      received 3.0 mg/kg D-amphetamine before and saline after sessions. Eight rats
      received saline before and after sessions. The final eight rats received saline
      before and 3.0 mg/kg D-amphetamine after sessions. All rats then experienced
      saline injections and extinction. During a reinstatement test, all rats received
      3.0 mg/kg D-amphetamine. D-Amphetamine significantly increased lever pressing for
      rats with prior exposure to amphetamine as a predictive cue for food (pre
      session) and for rats with no prior exposure to amphetamine. The effect was
      larger for rats with pre-session exposure to amphetamine than for rats with no
      previous exposure. Rats with exposure to amphetamine but not as a predictive cue
      for food (after sessions) did not show significant reinstatement of lever
      pressing. Therefore, the reinstating effects of amphetamine are not restricted to
      behavior previously maintained by amphetamine self-administration. In animal
      models of relapse, reinstatement of drug seeking could be due, in part, to
      discriminative and direct effects of self-administered drug.

PMID- 15472574
TI  - (-)-Adamantyl-delta8-tetrahydrocannabinol (AM-411), a selective cannabinoid CB1
      receptor agonist: effects on open-field behaviors and antagonism by SR-141716 in
      rats.
AB  - (-)-Adamantyl-Delta8-tetrahydrocannabinol (AM-411) is a 'classical' tricyclic
      cannabinoid CB1 receptor agonist in which the C-3 alkyl side-chain has been
      replaced with an adamantyl group. The compound is cannabinoid CB1 receptor
      subtype selective (CB1 Ki=6.86 nmol/l, CB2 Ki=52.0 nmol/l). We examined the
      effects of AM-411 alone and in combination with the cannabinoid CB1 receptor
      antagonist/inverse agonist, SR-141716, on open-field behaviors of rats. The
      lowest effective dose of AM-411, 3 mg/kg, suppressed ambulation (horizontal
      activity) and rearing (vertical activity) and increased circling frequency
      compared to vehicle control levels. Co-administration of SR-141716 normalized
      these changes. SR-141716 (3 and 5.6 mg/kg) also produced significant increases in
      scratching and grooming (both frequency and duration), effects that were not
      eliminated in the presence of AM-411. Coupled with previous drug discrimination
      data, the open-field profile of AM-411 suggests that this high-affinity CB1
      cannabinoid receptor agonist induces behavioral effects similar to the natural
      cannabinoid Delta9-tetrahydrocannabinol and different from (R)-methanandamide, a
      chiral analog of the endogenous ligand anandamide.

PMID- 15472583
TI  - Combination treatment of venous thoracic outlet syndrome: open surgical
      decompression and intraoperative angioplasty.
AB  - OBJECTIVE: Residual subclavian vein stenosis after thoracic outlet decompression
      in patients with venous thoracic outlet syndrome is often treated with
      postoperative percutaneous angioplasty (PTA). However, interval recurrent
      thrombosis before postoperative angioplasty is performed can be a vexing problem.
      Therefore we initiated a prospective trial at 2 referral institutions to evaluate
      the safety and efficacy of combined thoracic outlet decompression with
      intraoperative PTA performed in 1 stage. METHODS: Over 3 years 25 consecutive
      patients (16 women, 9 men; median age, 30 years) underwent treatment for venous
      thoracic outlet syndrome with a standard protocol at 2 institutions. Twenty-one
      patients (84%) underwent preoperative thrombolysis to treat axillosubclavian vein
      thrombosis. First-rib resection was performed through combined supraclavicular
      and infraclavicular incisions. Intraoperative venography and subclavian vein PTA
      were performed through a percutaneous basilic vein approach. Postoperative
      anticoagulation therapy was not used routinely. Venous duplex ultrasound scanning
      was performed postoperatively and at 1, 6, and 12 months. RESULTS: Intraoperative
      venography enabled identification of residual subclavian vein stenosis in 16
      patients (64%), and all underwent intraoperative PTA with 100% technical success.
      Postoperative duplex scans documented subclavian vein patency in 23 patients
      (92%). Complications included subclavian vein recurrent thrombosis in 2 patients
      (8%), and both underwent percutaneous mechanical thrombectomy, with restoration
      of patency in 1 patient. One-year primary and secondary patency rates were 92%
      and 96%, respectively, at life-table analysis. CONCLUSIONS: Residual subclavian
      vein stenosis after operative thoracic outlet decompression is common in patients
      with venous thoracic outlet syndrome. Combination treatment with surgical
      thoracic outlet decompression and intraoperative PTA is a safe and effective
      means for identifying and treating residual subclavian vein stenosis. Moreover,
      intraoperative PTA may reduce the incidence of postoperative recurrent thrombosis
      and eliminate the need for venous stent placement or open venous repair.

PMID- 15472584
TI  - Re-evaluation of iliac compression syndrome using magnetic resonance imaging in
      patients with acute deep venous thromboses.
AB  - BACKGROUND: The majority of proximal deep venous thromboses (DVTs) are thought to
      have propagated as a contiguous column from the calf veins. However, several
      authors have proposed that ileofemoral DVT commonly originates in the left common
      iliac vein (LCIV) at a site of compression by the overlying right common iliac
      artery (RCIA/LCIV compression). This mechanism could explain both the left-sided
      predominance of ileofemoral DVT and the finding that ileofemoral DVT frequently
      occurs either in the absence of calf vein thrombosis (isolated ileofemoral DVT)
      or is not contiguous with calf vein thrombosis (noncontiguous ileofemoral DVT).
      This mechanism remains unconfirmed. OBJECTIVES: The purpose of this study was to
      detect RCIA/LCIV compression using multimodal magnetic resonance imaging in
      thrombosed and patent iliac veins, to determine whether RCIA/LCIV compression
      occurs more frequently in cases of left ileofemoral DVT than other types of DVT,
      and to determine if RCIA/LCIV compression is specifically associated with left
      isolated and noncontiguous ileofemoral DVT. PATIENTS AND METHODS: This
      prospective study conducted at the 1355-bed University Hospital included 18
      patients with ileofemoral DVT, 23 with femoropopliteal DVT, 15 with isolated calf
      DVT recruited consecutively, and 28 control patients in whom DVT had been
      excluded. Interventions included magnetic resonance direct thrombus imaging
      (MRDTI), venous enhanced peak arterial magnetic resonance venography (VESPA) and
      magnetic resonance arteriography (MRA) within 48 hours of routine conventional
      venography (CV). RCIA/LCIV compression of patent LCIVs was assessed using VESPA
      and MRA; RCIA/LCIV compression of thrombosed LCIVs was assessed using MRDTI and
      MRA. The extent of calf and popliteal thrombosis was detected using CV; the
      extent of femoral and iliac thrombosis was detected using VESPA and MRDTI.
      RESULTS: RCIA/LCIV compression was more commonly detected in cases of left
      ileofemoral DVT (9/16 cases) than in cases of left femoropopliteal DVT (1/11
      cases; P = .018), right femoropopliteal DVT (2/12 cases; P = .054), left isolated
      calf DVT (1/9 cases; P = .037), right isolated calf DVT (0/6 cases; P = .046) and
      control patients (4/28 cases; P = .006). RCIA/LCIV compression was more commonly
      detected in cases of left isolated ileofemoral DVT (6/6 cases; P = .005), and
      cases of left noncontiguous ileofemoral DVT (2/2 cases; P = .067) than in cases
      in which thrombosis was contiguous from the calf to the iliac veins (1/8 cases).
      CONCLUSION: RCIA/LCIV compression was strongly associated with left ileofemoral
      DVT and was specifically associated with cases that involve independent
      ileofemoral thrombosis.

PMID- 15472585
TI  - Iliac compression syndrome and recanalization of femoropopliteal and iliac venous
      thrombosis: a prospective study with magnetic resonance venography.
AB  - OBJECTIVES: Poor iliac vein recanalization has been associated with compression
      of the left common iliac vein by the right common iliac artery (RCIA/LCIV
      compression); however, this finding has been difficult to confirm. In a baseline
      study, RCIA/LCIV compression was detected with magnetic resonance imaging in
      patients with deep venous thrombosis. We compared recanalization of left
      femoropopliteal and iliac thrombosis with and without RCIA/LCIV compression.
      METHODS: This was a prospective blinded study carried out in a 1355-bed
      university hospital. Thirty-one patients were recruited from consecutive cohorts
      of patients with iliofemoral and femoropopliteal DVT who underwent direct
      thrombus magnetic resonance imaging, venous enhanced peak arterial magnetic
      resonance venography, and magnetic resonance arteriography as part of the
      baseline study relating RCIA/LCIV compression to extent of thrombosis. Magnetic
      resonance venography was performed 6 weeks, 6 months, and 1 year after diagnosis
      of deep venous thrombosis. Femoropopliteal and iliac venous segments that were
      occluded at diagnosis were classified as occluded, partially occluded, or patent
      on follow-up scans. RESULTS: At 6-week follow-up, recanalization of all segments
      was incomplete. At both 6-month and 1-year follow-up, recanalization of left
      iliac segments associated with RCIA/LCIV compression was poorer compared with
      recanalization of left iliac segments not associated with compression (6 of 6
      occluded vs 1 of 6 occluded and 1 of 6 partially occluded at 6 months, P =.015; 6
      of 6 occluded vs 5 of 5 patent at 1 year, P = .002). This was due to complete
      failure of recanalization of left common iliac veins associated with RCIA/LCIV
      compression in 6 of 6 cases. All other iliac and femoropopliteal segments
      including left external iliac veins associated with RCIA/LCIV compression had
      high rates of recanalization at both 6 months and 1 year. CONCLUSION: RCIA/LCIV
      compression is associated with persistent occlusion of the left common iliac
      vein. The recanalization rate for all other femoropopliteal and iliac segments
      was high.

PMID- 15472586
TI  - Combined regional thrombolysis and surgical thrombectomy for treatment of
      iliofemoral vein thrombosis.
AB  - OBJECTIVE: In at least half of patients with iliofemoral deep vein thrombosis
      post-thrombotic syndrome develops when only anticoagulant therapy is given. We
      combined thrombolysis, applied under ischemic conditions,with surgical
      thrombectomy to restore patency and valve function. The technique and the short
      term and long-term results in 2 patient series are reported. METHODS: A catheter
      was inserted into a foot vein of the thrombosed leg, and the limb was excluded
      from the circulation with a pneumatic cuff placed on the thigh with the patient
      under general anesthesia. Urokinase (0.5 million-3 million IU) and heparin were
      infused and allowed to act for 30 minutes while the pelvic axis was cleared with
      a Fogarty catheter through an inguinal venotomy. The external iliac vein was then
      clamped and the cuff removed. Thrombi that detached from the wall were flushed
      out with reactive hyperemia and squeezed out with manual leg compression. The
      blood was retrieved, washed, and transfused back into the patient. Various
      additional procedures were performed to secure outflow. Two patient series are
      reported: 1 with 12 consecutive patients and 1 with 21 patients who were
      successfully treated 6 to 10 years previously. Follow-up data were obtained for
      all patients after 1 year and for 18 of 21 patients after 6 to 10 years. Patency
      and valve function were assessed with duplex scanning or venography. Studies of
      blood coagulation and the kinetics of urokinase were performed in 5 additional
      patients. RESULTS: Vein patency and valve function were restored in all
      consecutive patients. At 1 year none of the 33 patients had had recurrence, and
      none showed clinical signs of post-thrombotic syndrome. At 6 to 10 years 3 of 18
      patients had experienced another venous thromboembolism, but none in the treated
      leg. Sixteen legs were asymptomatic without compression therapy, and 2 had venous
      claudication. Coagulation studies showed a trace concentration of urokinase and a
      mild decrease in fibrinogen in the systemic circulation. The concentration of
      urokinase in blood collected from the treated leg was only 1% of that infused.
      CONCLUSION: Regional thrombolysis combined with surgical thrombectomy is
      relatively easy to perform and seems safe. Vein patency and valve function were
      restored, and post-thrombotic syndrome was prevented. Additional procedures to
      overcome pelvic vein obstructions were required in 11 of 33 patients (33%). The
      procedure should be tested against standard anticoagulation therapy in patients
      with acute iliofemoral thrombosis.

PMID- 15472587
TI  - Perforator vein incompetence in chronic venous disease: a multivariate regression
      analysis model.
AB  - OBJECTIVES: In the presence of superficial and deep vein insufficiency the
      effects, if any, of concurrent incompetent perforator veins (IPVs) on clinical
      status are masked. On the basis of multivariate regression analysis, this study
      examines the significance of perforator vein incompetence across the clinical
      classes of CEAP (C-class CEAP ) in relation to the superficial and deep systems,
      and assesses the role of factors implicated in the presence and number of IPVs in
      chronic venous disease (CVD). METHODS: The study included 525 limbs in 360
      patients, ages 17 to 96 years, referred for investigation of CVD. The protocol
      entailed history taking, physical examination, and duplex scanning (reflux > 0.5
      s), with emphasis on IPVs. Exclusion criteria included peripheral vascular
      disease, unrelated edema, severe chronic obstructive pulmonary disease, and
      recent (< 1 year) deep vein thrombosis (DVT). RESULTS: Limbs were stratified as C
      0 , 84; C 1 , 25; C 2 , 231; C 3 , 66; C 4 , 48; C 5 , 23; and C 6 , 48. C-class
      CEAP was separately regressed with age ( P < .001), sex ( P < .25), contralateral
      CVD ( P < .2), CVD recurrence ( P = .022), previous DVT ( P < .001), superficial
      vein reflux ( P < .001); deep vein reflux ( P < .001), perforator vein reflux ( P
      < .001), and number of IPVs ( P < .001). In an optimized multivariate regression
      analysis of C class CEAP with all significant variables combined, age ( P <
      .001), previous DVT ( P = .017), superficial vein reflux ( P < .001), deep vein
      reflux ( P < .001), and number of IPVs ( P = .008) emerged as predictors of CVD
      severity (CEAP), based on the equation C class CEAP = -0.2807 + 0.028013 Age +
      0.58530 Previous DVT + 0.3450 Superficial vein reflux + 0.17781 Deep Reflux +
      0.14537 IPVs ( R 2 = 37.4%; P < .001). Perforator incompetence was predicted by
      superficial vein reflux ( P < .001) and deep vein reflux ( P = .044), age ( P =
      .019), CVD recurrence ( P = .038), and sex ( P = .018), as follows: Perforator
      incompetence = -0.2532 + 0.006457 Age + 0.41366 Superficial reflux + 0.06766 Deep
      reflux + 0.2450 CVD recurrence - 0.21310 Sex ( R 2 = 33.3%; P < .001). Number of
      IPVs per limb was best associated with superficial reflux ( P < .001) and deep
      reflux ( P = .023), linked as IPVs = - 0.11789 + 0.41323 Superficial reflux +
      0.07646 Deep reflux ( R 2 = 26.1%; P < .001). CONCLUSION: Perforator incompetence
      proved to be a significant factor for determination of CVD severity according to
      C-class CEAP , withstanding the conspicuous confounding effects of the
      superficial and deep venous systems. Perforator incompetence was significantly
      linked to aging, superficial or deep vein incompetence, recurrence of superficial
      disease, and sex, whereas the IPV number, regardless of location, depended on the
      presence of superficial or deep venous reflux.

PMID- 15472588
TI  - Causes of varicose vein recurrence: late results of a randomized controlled trial
      of stripping the long saphenous vein.
AB  - BACKGROUND: The purpose of this study was to investigate the long-term outcomes
      following stripping of the long saphenous vein during primary varicose vein
      surgery and to identify factors which may predict recurrence and the need for
      reoperation. METHODS: The original study was designed as a randomized trial of
      100 patients (133 legs) who underwent saphenofemoral ligation with or without
      long saphenous vein stripping. After invitation 11 years later, 51 patients (74
      legs) underwent clinical review and duplex imaging and completed an Aberdeen
      Varicose Vein Symptom Severity Score (AVVSSS). The hospital notes of the original
      cohort of patients were used to compile cumulative data and assess predictive
      factors. RESULTS: A cumulative total of 83 legs had developed clinically
      recurrent varicose veins by 11 years (62%). There was no statistically
      significant difference between the ligation-only and the stripping groups.
      Reoperation was required for 20 of 69 legs that underwent ligation alone compared
      with 7 of 64 legs that had additional long saphenous vein stripping (relative
      risk [RR], 2.65; 95% confidence interval, 1.20 to 5.84; P = .012). By life table
      analysis, freedom from reoperation at 11 years was 70% after ligation, compared
      with 86% after stripping ( P = .01). The presence of neovascularization (RR,
      2.88; P = .15) , an incompetent superficial vessel in the thigh (RR, 3.24; P =
      .03) or an incompetent saphenofemoral junction on duplex imaging at 2 years
      postoperatively (RR, 4.89; P = .0001) increased the risk of a patient's
      developing clinically recurrent veins. Patients with visible recurrent varicose
      veins had a significantly worse AVVSSS ( P = .001). CONCLUSION: Stripping the
      long saphenous vein is recommended as part of routine varicose vein surgery as it
      reduced the risk of reoperation by 60% after 11 years, although it did not reduce
      the rate of visible recurrent veins.

PMID- 15472589
TI  - Axillary to saphenous vein bypass for treatment of central venous obstruction in
      patients receiving dialysis.
AB  - OBJECTIVE: Venous hypertension due to subclavian or innominate vein stenosis
      coexisting with a functioning arteriovenous access in the ipsilateral arm is a
      complex problem in patients undergoing hemodialysis. Therapeutic solutions must
      optimally relieve symptoms, permit use of the angioaccess, and carry minimal
      surgical risk. The purpose of this study was to evaluate a simple surgical
      option, bypassing central venous obstruction to the great saphenous vein.
      METHODS: Eight patients undergoing hemodialysis with severe symptoms and signs of
      venous hypertension due to subclavian or innominate vein obstruction and
      ipsilateral arteriovenous fistula or graft underwent axillosaphenous bypass via a
      subcutaneous 8-mm polytetrafluoroethylene bridge graft. RESULTS: No
      intraoperative or immediate postoperative morbidity was observed. Early and 6
      month patency rates were 100% and 87.5%, respectively. All patients reported
      improvement of symptoms, and the angioaccess was usable in all cases. Average
      follow-up was 21.5 months. One patient had a relapse at 5 months, which
      necessitated revision of the graft-saphenous vein anastomosis. CONCLUSION:
      Bypassing a central vein occlusion to the saphenous vein relieves symptoms of
      venous hypertension and prolongs use of the hemodialysis angioaccess.

PMID- 15472590
TI  - C-reactive protein and red cell aggregation correlate with late venous function
      after acute deep venous thrombosis.
AB  - OBJECTIVE: Risk factors leading to development and subsequent progression of
      chronic venous insufficiency after acute deep venous thrombosis (DVT) are only
      partially identified. Inflammation and rheologic abnormalities might have a
      causative role. The purpose of this study was to investigate C-reactive protein
      (CRP), D -dimer, and blood rheologic parameters in patients after acute DVT in
      relation to clinical outcome. SUBJECTS AND METHODS: Patients with a history of
      acute proved DVT underwent clinical examination and duplex ultrasound scanning of
      the veins, and Venous Clinical Severity Score (VCSS) and Venous Segmental Disease
      Score (VSDS) were calculated. Further, CRP, D -dimer, and several rheologic
      parameters were determined and related to outcome as assessed with venous scores.
      RESULTS: Forty-three patients were examined 28 (median) months after the index
      event. Patients had higher CRP ( P < .001), D -dimer ( P < .001), red blood cell
      aggregation ( P < .01), fibrinogen concentration ( P < .01), and leukocyte count
      ( P < .05) than did healthy control subjects. CRP and red blood cell aggregation
      were positively correlated with VCSS ( r = 0.42 and P < .01, and r = 0.30 and P <
      0.05, respectively). Multivariate regression analysis showed that the relation
      between CRP and VCSS was independent of other laboratory and rheologic parameters
      and of age, total thrombus load, duration of compression therapy after the index
      event, recurrence, recanalization, and presence of comorbid conditions ( P <
      .05). CONCLUSIONS: CRP is independently related to the severity of venous
      dysfunction in patients after acute DVT. Chronic inflammation as well as changes
      in blood rheologic parameters may be causally involved in the development of
      chronic venous insufficiency occurring in the medium-term and long-term course
      after acute DVT.

PMID- 15472591
TI  - Prevalence, risk factors, and clinical patterns of chronic venous disorders of
      lower limbs: a population-based study in France.
AB  - OBJECTIVES: The goals of this study were to document the prevalence of varicose
      veins, skin trophic changes, and venous symptoms in a sample of the general
      population of France, to document their main risk factors, and to assess
      relationships between them. METHODS: This cross-sectional epidemiologic study was
      carried out in the general population of 4 locations in France: Tarentaise,
      Grenoble, Nyons, and Toulon. Random samples of 2000 subjects per location were
      interviewed by telephone, and a sub-sample of subjects completed medical
      interviews and underwent physical examination, and the presence of varicose
      veins, trophic changes, and venous symptoms was recorded. RESULTS: Prevalence of
      varicose veins, skin trophic changes, and venous symptoms was not statistically
      different in the 4 locations. In contrast, sex-related differences were found:
      varicose veins were found in 50.5% of women versus 30.1% of men ( P < .001);
      trophic skin changes were found in 2.8% of women versus 5.4% of men ( P = NS),
      and venous symptoms were found in 51.3% of women 51.3% versus 20.4% of men ( P <
      .001). Main risk factors for varicose veins were age and family history in both
      sexes, and pregnancy in women. Female sex was a significant factor only for non
      saphenous varicose veins. Varicose veins, age, and pitting edema were the most
      significant risk factors for trophic skin changes. The risk factors for venous
      symptoms were female sex, varicose veins, and prolonged sitting or standing. A
      negative relationship with age was found in women. CONCLUSION: Our results show a
      high prevalence of chronic venous disorders of the lower limbs in the general
      population of France, with no significant geographic variations. They also
      provide interesting insights regarding the association of varicose veins, skin
      trophic changes, and venous symptoms.

PMID- 15472592
TI  - Vascular surgery training in the United States, 1994 to 2003.
AB  - OBJECTIVE: The purpose of this study was to analyze the use of operative training
      resources for vascular surgery residents (VSRs) and general surgery residents
      (GSRs) over the past 10 years in the United States, to address questions
      concerning adequate endovascular versus open surgical training and the potential
      to expand the number of VSRs to meet future workforce needs. METHODS: National
      operative data from the Residency Review Committee for Surgery (RRC) were
      analyzed for all vascular surgery (VS) and general surgery (GS) training programs
      from 1994 to 2003. GSR experience in programs with and without associated VS
      programs was also compared. RESULTS: Mean total VS volume per VSR increased from
      220 operations in 1994 to 368 in 2003, owing to the addition of 140 endovascular
      procedures by 2003. GSR volume was more stable, with 117 mean total VS operations
      in 1994 and 122 in 2003. This volume was distributed as approximately 50% major
      open VS operations for both VSR and GSR. In addition, 39% of VSR experience was
      endovascular, whereas 32% of GSR experience was vascular access. The average VSR
      performed 2.7 times more major open VS operations than each GSR, but because of
      the 10-fold greater number of GSRs, VSRs performed only 20% of the total major
      operations available for VS training. Selective procedures, such as renal
      revascularization and open infrarenal abdominal aortic aneurysm repair decreased
      over time, while endovascular abdominal aortic aneurysm repair increased
      dramatically, accounting for 46% of aortic aneurysm repairs per VSR in 2003. The
      mean volume of total interventional procedures per VSR in 2003 was 152 diagnostic
      and 213 therapeutic. GSRs in programs with and without an associated VS program
      had very similar operative volumes. CONCLUSIONS: Interventional procedures have
      increased VSR operative volume by 50% in recent years, with only a 12% decrease
      in major open operations. Nearly all VSRs currently meet RRC minimum requirements
      for open and endovascular procedures. Mean GSR operative volume has been stable,
      and far exceeds RRC minimum requirements. Based on the number of major open
      vascular operations available for training in 2003, the current number of VSR
      positions could be increased by 50% if GSR operative volume was decreased by 15%.
      However, increased interventional volume would also be required, for which there
      is competition with other specialties.

PMID- 15472593
TI  - Endovascular treatment of thoracic aortic diseases: combined experience from the
      EUROSTAR and United Kingdom Thoracic Endograft registries.
AB  - PURPOSE: The objective of this study was to assess the initial and 1-year outcome
      of endovascular treatment of thoracic aortic aneurysms and dissections collated
      in the European Collaborators on Stent Graft Techniques for Thoracic Aortic
      Aneurysm and Dissection Repair (EUROSTAR) and the United Kingdom Thoracic
      Endograft registries. METHODS: Four hundred forty-three patients underwent
      endovascular repair of thoracic aortic disease between September 1997 and August
      2003 (EUROSTAR, 340 patients; UK, 103 patients). Patients represented 4 major
      disease groups: degenerative aneurysm (n = 249), aortic dissection (n = 131),
      false anastomotic aneurysm (n = 13), and traumatic aortic injury (n = 50).
      RESULTS: Mean age in the entire study group was 63 years. Fifty-two percent of
      patients were deemed at high risk for open surgery because of major comorbidity.
      Sixty percent of patients underwent an elective procedure, and 35% required
      emergency treatment. Conventional indications for treatment of aortic dissection,
      including aortic expansion, continuous pain, rupture, or symptoms of branch
      occlusion constituted the basis for endograft placement in 57% of patients,
      whereas in 43% of patients aortic dissections were asymptomatic. Primary
      technical success was obtained in 87% of patients with degenerative aneurysm and
      in 89% with aortic dissection. Paraplegia was a postoperative complication in
      4.0% of patients with degenerative aneurysm and 0.8% of patients with aortic
      dissection (not significant). Thirty-day mortality in the entire study group was
      9.3%, with mortality rates after elective procedures of 5.3% for degenerative
      aneurysms and 6.5% for aortic dissection. Mortality for degenerative aneurysm
      after emergency repair was higher (28%; P <.0001) then after elective procedures.
      For aortic dissection the emergency repair rate was 12% (not significant compared
      with elective repair of aortic dissection, and P = .025 compared with emergency
      repair of degenerative aneurysm). One-year follow-up was complete in 195
      patients. The outcome at 1 year was more favorable for aortic dissection than for
      degenerative aneurysm with regard to aortic expansion (0% vs 15%; P = .001) and
      late survival (90% vs 80%; P = .048). In the groups with false anastomotic
      aneurysm and traumatic aortic injury, 30-day mortality rates were 8% and 6%,
      respectively. CONCLUSION: This multicenter experience demonstrates acceptable
      rates for operative mortality and paraplegia after endovascular repair of
      thoracic aortic disease. Outcome after 30 days and 1 year was more favorable for
      aortic dissection than for degenerative aneurysm. However, the durability of this
      technique is currently unknown, and continued use of registries should provide
      data from long-term follow-up.

PMID- 15472595
TI  - Naloxone lowers cerebrospinal fluid levels of excitatory amino acids after
      thoracoabdominal aortic surgery.
AB  - OBJECTIVE: Although naloxone has been used to prevent ischemic spinal cord injury
      (SCI), its effect on excitatory amino acids (EAAs) has not been understood. We
      investigated the clinical significance of naloxone by measuring EAAs in the
      cerebrospinal fluid (CSF) in patients undergoing thoracoabdominal aortic surgery.
      METHODS AND SUBJECTS: Twenty-seven patients (15 men and 12 women; mean age, 66 +/
      12 years) undergoing prosthetic replacement of the thoracoabdominal aorta (n =
      19) or the descending thoracic aorta (n = 8) from April 1997 to June 2003 under
      distal perfusion and mild hypothermia were enrolled in this cohort study with
      historical controls. Their etiology was 7 dissections and 20 nondissections. In
      16 patients (naloxone group), intravenous infusion of naloxone (1 microg/kg/h)
      was continued until the patients became alert. In the remaining 11 patients
      (control group) naloxone was not given. CSF drainage was used in all patients.
      CSF levels of EAAs, glutamate, aspartate, and glycine were measured at 6 points
      in time until 72 hours postoperatively, using a high-performance liquid
      chromatography method. RESULTS: In 5 patients with SCI (2 patients in control
      group, 3 in naloxone group), CSF levels of glutamate and glycine continued to
      increase even at 72 hours postoperatively, and were significantly more elevated
      than those in patients without SCI ( P < .0001, glutamate; P = .0006, glycine).
      Postoperative maximum levels of CSF glutamate and glycine were also significantly
      higher in patients with postoperative SCI than in patients without SCI
      (glutamate: 215.3% +/- 158.6% vs 32.9% +/- 37.3% increase from baseline, P <
      .0001; glycine: 309.1% +/- 218.2% vs 89.2% +/- 103.1% increase from baseline, P =
      .0036). CSF levels of glutamate and aspartate in naloxone group were
      significantly lower than those in control group ( P = .0161, glutamate; P <
      .0001, aspartate). Postoperative maximum level of CSF aspartate was also
      significantly lower in the naloxone group than in the control group (8.3% +/-
      75.5% vs 119.7% +/- 120.6% increase from baseline, P = .0077). In multivariate
      logistic regression analysis, postoperative maximum CSF glutamate >100% from
      baseline ( P < .001) and postoperative maximum level of CSF glycine ( P =
      .005)were identified as the independent risk factors for SCI. Both SCI ( P <
      .001) and postoperative maximum level of CSF glycine ( P = .005) were the
      independent predictors for postoperative maximum level of CSF glutamate >100%
      from baseline. CONCLUSIONS: CSF levels of EAAs are elevated in patients with SCI.
      CSF glutamate is the strongest independent predictor of SCI. Naloxone is
      effective in lowering CSF levels of EAAs.

PMID- 15472596
TI  - Patients with abdominal aortic aneurysm: are we missing the opportunity for
      cardiovascular risk reduction?
AB  - INTRODUCTION: Antiplatelet agents, 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors (statin drugs), angiotensin converting enzyme (ACE)
      inhibitors, and beta-adrenergic receptor blockers (beta-blockers) reduce
      cardiovascular risk and mortality in patients with specific manifestations of
      cardiovascular disease and risk factors. Occlusive arterial disease, in
      particular, coronary heart disease, is prevalent in patients with abdominal
      aortic aneurysm (AAA) and results in reduced life expectancy. The purpose of this
      study was to investigate the prevalence of cardiovascular disease and risk
      factors in patients with AAA. In particular, numbers of patients in whom
      pharmacologic therapy is indicated and numbers of patients who are receiving
      adequate treatment were determined. METHODS: This was a prospective study of 313
      patients with AAA in Leicestershire over the 15 months between September 2002 and
      December 2003. RESULTS: Data that enabled determination of an indication for
      antiplatelet agents and statin drugs were available for 262 patients (84%), and
      for a beta-blocker and ACE inhibitor for 313 patients (100%). An antiplatelet
      agent was indicated in 242 of 262 patients (92%), a statin drug was indicated in
      196 of 262 patients (75%), a beta-blocker was indicated in 107 of 313 patients
      (34%), and an ACE inhibitor was indicated in 178 of 313 patients (57%). In
      patients with an indication, 146 of 242 patients (60%) were using an antiplatelet
      agent, 81 of 196 (41%) were using a statin drug, 41 of 313 (38%) were using a
      beta-blocker, and 69 of 313 (39%) were using an ACE inhibitor. CONCLUSION:
      Cardiovascular disease, for which there is evidence for the survival benefit of
      pharmacologic risk reduction, is prevalent in patients with AAA. The data show
      that current treatment of cardiovascular risk is suboptimal and could be
      improved, with an expected reduction in cardiovascular morbidity and mortality.

PMID- 15472597
TI  - Effects of bilateral hypogastric artery interruption during endovascular and open
      aortoiliac aneurysm repair.
AB  - PURPOSE: Hypogastric artery interruption is sometimes required during aortoiliac
      aneurysm repair. We have not experienced some of the life-threatening
      complications of pelvic ischemia reported by others. Therefore we analyzed our
      experience to identify factors that help minimize pelvic ischemia with unilateral
      and bilateral hypogastric artery interruption. METHODS: From 1995 to 2003, 48
      patients with aortoiliac aneurysm required interruption of both hypogastric
      arteries as part of endovascular (n = 32) or open surgical (n = 16) repair.
      During endovascular aneurysm repair coils were placed at the origin of the
      hypogastric arteries, and bilateral hypogastric artery interruptions were staged
      at 1 to 2 weeks when possible. Open surgery necessitated oversewing or excluding
      the origins of the hypogastric arteries and extending the prosthetic graft to the
      external iliac or femoral artery. Collateral branches from the external iliac and
      femoral arteries were preserved, and patients received systemic heparinization
      (50 units/kg). RESULTS: There was no buttock necrosis, ischemic colitis requiring
      colon resection, or death with the bilateral hypogastric artery interruption.
      Initially buttock claudication developed in 20 patients (42%), but persisted in
      only 7 patients (15%) at 1 year. New onset of impotence occurred in 4 of 28
      patients (14%), and there were no neurologic deficits. CONCLUSIONS: Bilateral
      hypogastric artery interruptions can be accomplished with limited morbidity. When
      hypogastric artery interruption is needed during endovascular aneurysm repair,
      certain principles help minimize pelvic ischemia. These include hypogastric
      artery interruption at its origin to preserve the pelvic collateral vessels,
      staging bilateral hypogastric artery interruptions when possible, preserving
      collateral branches from the femoral and external iliac arteries, and providing
      adequate heparinization of the patient during these procedures.

PMID- 15472598
TI  - Ischemic complications after endovascular abdominal aortic aneurysm repair.
AB  - OBJECTIVES: Limb and pelvic ischemia are known complications after endovascular
      abdominal aortic aneurysm repair (EVAR). The objective of this paper is to
      present our experience with the incidence, presentation, and management of such
      complications. METHODS: Over 9 years 311 patients with aortic aneurysms underwent
      EVAR. A retrospective review identified 28 patients (9.0%) with ischemic
      complications. RESULTS: Among 28 patients with ischemic complications, 21 had
      lower extremity ischemia and 7 had pelvic ischemia: colon (n = 4), buttock (n =
      2), and spinal cord (n = 2). Of the 21 patients with lower extremity ischemia, 15
      had limb occlusions (71.4%), 3 due to embolization (14.7%) and 3 the result of
      common femoral artery thromboses (14.7%). Limb occlusions were manifested as
      severe acute arterial ischemia (n = 6), rest pain (n = 3), intermittent
      claudication (n = 5), and decreased femoral pulse (n = 1). Limb occlusions were
      managed with thrombectomy and stent placement (n = 4), femorofemoral bypass (n =
      7), eventual explantation because of persistent endoleak (n = 1), and expectant
      management (n = 3). The 3 patients with occlusions managed expectantly all had
      intermittent claudication, which has subsequently improved. In the 6 patients
      with lower extremity ischemia due to embolization or common femoral artery injury
      presentation was acute, and embolectomy was performed, followed by femoral artery
      endarterectomy and patch angioplasty or placement of an interposition graft. One
      patient who had a prolonged postoperative course including cardiac arrest
      subsequently required distal bypass and ultimately above- knee amputation. Among
      the 7 patients with pelvic ischemia, 2 patients had unilateral hypogastric artery
      embolization before the original surgery. Among the patients with colonic
      ischemia, 3 were seen immediately postoperatively, and required colectomy and
      colostomy. Two patients who required urgent colectomy subsequently had multiple
      organ failure, and died in the perioperative period. One patient had abdominal
      pain 1 week after surgery, which was managed with bowel rest, with subsequent
      improvement. In 2 patients spinal cord ischemia developed immediately after
      surgery, which resulted in persistent paraplegia. Buttock ischemia developed in 2
      patients, 1 of whom required fasciotomy because of gluteal compartment syndrome,
      and had transient renal failure. CONCLUSIONS: Ischemic complications are not
      uncommon after EVAR, and may exceed the incidence with open surgical repair. Limb
      ischemia is most often a result of limb occlusion, and can be successfully
      managed with standard interventions. Pelvic ischemia often results from
      atheroembolization despite preservation of hypogastric arterial circulation.
      Colonic and spinal ischemia are associated with the highest morbidity and
      mortality.

PMID- 15472599
TI  - Direct intra-aneurysm sac pressure measurement using tip-pressure sensors: in
      vivo and in vitro evaluation.
AB  - OBJECTIVE: Direct intra-aneurysm sac pressure measurement with percutaneous
      translumbar puncture is a new method for follow-up after endovascular aneurysm
      repair. The purpose of this study was to evaluate a tip-pressure sensor system
      for intra-aneurysm pressure measurement in an in vitro aneurysm model and in vivo
      in patients by studying intraobserver variability. METHODS: We used 0.014-inch
      guide wire-mounted tip-pressure sensors. For the in vitro aneurysm model,
      saccular aneurysms filled with thrombus were inserted in a left-heart-driven
      aneurysm model. Pressure was measured simultaneously with guide wire pressure
      sensors in the lumen of the model and within the aneurysm thrombus. In vivo,
      intraobserver variability was evaluated with double percutaneous translumbar
      puncture of the abdominal aortic aneurysm (AAA) with pressure measurement in 15
      patients (14 men, 1 woman; median age, 75 years [63-80 years]; median AAA
      diameter, 55 mm [47-80 mm]) at a median of 32 months (2-100 months) after
      endovascular aneurysm repair. Mean pressure index was calculated as the
      percentage of mean intraaneurysm pressure relative to simultaneous mean systemic
      pressure. RESULTS: In vitro, the difference in pressure between the tip-sensor
      measurements and the pressure output of the aneurysm model was 2 mm Hg (1-4 mm
      Hg) when the output varied between 150/50 and 200/100 mm Hg (n = 90). Mean
      pressure in the lumen of the model and within the aneurysm thrombus differed by 1
      mm Hg (-5-15 mm Hg (n = 10). In vivo, intraobserver variability of mean pressure
      index (Bland-Altman plot) was 0% (-7%-17%; n = 15%). CONCLUSION: Direct intra
      aneurysm sac pressure measurement with tip-pressure sensors mounted on 0.014-inch
      guide wires is a reliable and reproducible technique for measuring intra-AAA
      pressure both in vitro and in vivo.

PMID- 15472600
TI  - Diffusion of new technology for the treatment of renovascular hypertension in the
      United States: surgical revascularization versus catheter-based therapy, 1988
      2001.
AB  - BACKGROUND: Trends in the management of renovascular hypertension were evaluated
      by using a representative national database to determine whether a shift in
      treatment technology and outcomes has occurred. METHODS: Clinical information
      regarding the treatment of renovascular hypertension in 5433 patients from 1988
      to 2001 was derived from the Nationwide Inpatient Sample (NIS) database. Patients
      were classified into 3 groups: combined aortic and renal revascularization,
      isolated renal revascularization, and catheter-based procedures (angioplasty with
      or without stenting). Population-based trends were determined by using sampling
      weights for each year to estimate the total number of each intervention in the
      United States. Outcomes were compared using multivariate logistic regression
      analysis for risk-adjustment. RESULTS: A 73% decrease in combined aortic and
      renal revascularizations ( P = .033) and a 56% decrease in isolated renal
      revascularizations ( P < .001) occurred during the study period. Catheter-based
      procedures have increased 173% from 0.4 to 1.1 procedures per 100,000 adults
      during this same time period ( P < .001). Predictors favoring catheter-based
      treatment were admission acuity, increasing age, nonwhite race, and high
      socioeconomic status. Predictors of mortality for all 3 treatment groups included
      increasing age, emergent admission, and nonwhite race. CONCLUSIONS: A significant
      change in the management of patients with renovascular hypertension has occurred,
      with a shift towards less invasive catheter-based interventions. A better
      understanding of the diffusion of this technology in the treatment of individuals
      with renovascular hypertension will influence the training and distribution of
      future vascular specialists responsible for these patients.

PMID- 15472601
TI  - Optimizing infrainguinal arm vein bypass patency with duplex ultrasound
      surveillance and endovascular therapy.
AB  - OBJECTIVE: Infrainguinal bypass grafting with arm vein is associated with lower
      patency rates compared with saphenous vein conduits. In this study the effect of
      a duplex ultrasound surveillance program to enable identification and treat graft
      lesions with open or endovascular repair on patency was analyzed. METHODS: Over 9
      years 89 infrainguinal arm vein (26% spliced vein) bypasses were performed to
      treat critical lower limb ischemia in 89 patients without adequate saphenous vein
      conduits. Seventy-six (85%) of the bypasses were repeat procedures. Grafts were
      assessed at operation with duplex ultrasound scanning, then enrolled in a
      surveillance program. Graft stenoses with peak systolic velocity greater than 300
      cm/s and velocity ratio greater than 3.5, detected at duplex ultrasound scanning,
      were repaired with percutaneous transluminal balloon angioplasty (PTA) if
      specific criteria were met, including greater than 3 months since primary
      procedure, lesion length less than 2 cm, and graft diameter greater than 3.5 mm,
      or with open surgical repair for early appearing or extensive graft lesions.
      RESULTS: During a mean 26-month follow-up, duplex surveillance resulted in a 48%
      (43 bypasses) intervention rate. Primary patency rate was 43% at 3 years. Twenty
      six (43%) of 61 lesions identified and repaired met criteria for PTA; the
      remaining 35 graft lesions (stenosis, n = 30; vein graft aneurysm, n = 5) were
      surgically corrected with vein patch angioplasty (n = 15), interposition grafting
      (n = 13), jump graft bypass (n = 6), or open repair (n = 1). At 3 years the
      assisted primary patency rate was 91% (7 graft failures). Multiple interventions
      were performed in 18 (42%) revised grafts because of metachronous (n = 6) or
      repair site stenosis (n = 12). In 18 graft interventions (PTA, n = 9; surgery, n
      = 9) recurrent stenosis developed, and endovascular therapy was used in one third
      (n = 6). At 3 years the stenosis-free patency rate for PTA (48%) and surgically
      repaired (53%) graft lesions was similar. CONCLUSIONS: Arm veins used in lower
      limb bypass procedures are prone to development of stenosis and aneurysm, lesions
      easily detected with a life-long duplex ultrasound surveillance program.
      Excellent long-term patency (91%) was achieved despite graft intervention being
      performed in nearly half of all bypasses and one third of revised grafts.
      Endovascular treatment was possible in half of all graft stenosis, with outcomes
      similar to those with surgical repair.

PMID- 15472602
TI  - Prospective randomized study on reversed saphenous vein infrapopliteal bypass to
      treat limb-threatening ischemia: common femoral artery versus superficial femoral
      or popliteal and tibial arteries as inflow.
AB  - PURPOSE: Use of inflow sources distal to the common femoral artery (CFA) for
      bypass to infrapopliteal arteries is a compromise measure when the length of the
      vein is not adequate. The purpose of this study was to compare the clinical
      outcome of vein infrapopliteal bypass arising from the CFA and from the distal
      superficial femoral or popliteal and tibial arteries in patients with limb
      threatening ischemia. METHODS: Over 13 years, 160 vein infrapopliteal vein bypass
      procedures (160 patients) were randomized into 2 groups, 80 with inflow arising
      from the CFA (group 1) and 80 with inflow from below the CFA (group 2). Patency
      and limb salvage rates were assessed with the Kaplan-Meier method. All patients
      underwent graft surveillance at discharge and at 30 days and 6 months after
      surgery, then every 6 months thereafter. Follow-up ranged from 30 days to 127
      months (mean, 49 months). RESULTS: Groups were similar with regard to age, sex,
      and most atherosclerotic risk factors. Gangrene as an indication for surgery was
      statistically more frequent in group 1 (73.7% vs 48.7%; P = .002), whereas
      nonhealing ulcer and rest pain were statistically more frequent in group 2
      (respectively, 51.2% vs 25%; P = .001 and 46.2% vs 28.7%; P = .03). No patients
      died during the perioperative (30 days) period. At 1, 3, and 5 years patency and
      limb salvage rates were comparable between groups, tending toward significance
      for the 5-year primary patency rate (73% vs 57%; P = .08). CONCLUSIONS: In the
      absence of significant proximal disease, infrapopliteal revascularization arising
      distal to the CFA can ensure patency and limb salvage rates statistically similar
      to those with use of the CFA. Moreover, procedures arising distal to the CFA
      required fewer graft revisions to maintain patency of failing grafts.

PMID- 15472603
TI  - Exercise training enhances endogenous fibrinolysis in peripheral arterial
      disease.
AB  - PURPOSE: Acute clinical events resulting from atherosclerosis (myocardial
      infarction, stroke) are associated with impaired endogenous fibrinolysis, the
      system by which the body lyses inappropriately formed thrombus. Endurance
      exercise training improves fibrinolysis in normal subjects and those with
      coronary artery disease. The hypothesis of this study was that exercise training
      would improve fibrinolysis in subjects with peripheral arterial disease (PAD).
      METHODS AND RESULTS: Twenty-one men with intermittent claudication (IC-EX)
      underwent treadmill exercise training for 6 months. Twenty age-matched male
      subjects with IC were followed for the same period (IC-NONEX). Fibrinolytic
      activity was measured prior to entry into exercise or "usual care," and at the
      completion of the study period. Fibrinolysis was quantified by measurement of the
      activity levels of tissue plasminogen activator (tPA, the activator of
      fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1), using
      an amidolytic method. Fibrinolysis, quantified as increased PAI-1 activity, was
      reduced in both claudicant groups relative to healthy controls at baseline. After
      6 months of exercise, subjects in the IC-EX group experienced significant
      improvements in fibrinolytic activity, manifested as a 23% decrease in PAI-1
      activity and a 28% increase in tPA activity. No changes occurred in the IC-NONEX
      group. In the IC-EX group, subjects with the highest initial PAI-1 values
      experienced the greatest decreases in PAI-1 activity and thus the greatest
      benefit from exercise. CONCLUSIONS: Patients with PAD have impaired fibrinolytic
      activity, manifested primarily as increases in the inhibitor of fibrinolysis, PAI
      1. Six months of exercise training reduced these impairments, and may serve as an
      intervention to reduce cardiovascular mortality and morbidity in these patients.

PMID- 15472604
TI  - Technical challenges in a program of carotid artery stenting.
AB  - OBJECTIVES: Successful carotid artery stenting (CAS) involves gaining access to
      the common carotid artery, characterizing and crossing the lesion, deploying an
      anti-embolic device and stent, and retrieving the anti-embolic device. These
      steps are critical determinants of the complexity of the procedure. The frequency
      with which technical challenges are encountered during CAS is ill-defined. The
      purpose of this investigation was to review the incidence and types of technical
      challenges encountered during CAS and determine their effect on outcome. METHODS:
      Data were prospectively collected for 194 consecutive CAS procedures (177
      patients) and separated into group 1, standard CAS technique, and group 2,
      procedures with technical challenges requiring modifications to the technique.
      Technical challenges were defined as difficult femoral arterial access
      (aortoiliac occlusive disease), complex aortic arch anatomy (elongated or bovine
      arch, deep takeoff of the innominate artery, tandem stenoses (CCA, innominate
      artery), difficult internal carotid artery anatomy (tortuosity, high-grade
      stenosis), and circumferential internal carotid artery calcification. The
      incidence of technical challenges, types of technical modifications required, and
      effect on outcomes were determined. RESULTS: Fifty technically challenging
      situations (26%) were encountered in 194 CAS procedures (group 2), which required
      advanced technical skills. Standard methods were used in the other 144 procedures
      (group 1, 74%). No significant differences in 30-day stroke and death rates were
      noted between the groups (group 1, 3.1%; group 2, 2.0%; P = .564). CONCLUSIONS:
      Twenty-six percent of the procedures required a modification in the standard
      technique for successful CAS. Circumferential calcification and severe tortuosity
      continue to be relative contraindications to CAS. Recognition of these technical
      challenges and increasing facility with the methods to manage them will enable
      expanded use of CAS without increased morbidity and mortality.

PMID- 15472605
TI  - Long-term survival after vascular surgery: specific influence of cardiac factors
      and implications for preoperative evaluation.
AB  - OBJECTIVE: We sought to identify specific determinants of long-term cardiac
      events and survival in patients undergoing major arterial operations after
      preoperative cardiac risk stratification by American College of
      Cardiology/American Heart Association guidelines. A secondary goal was to define
      the potential long-term protective effect of previous coronary revascularization
      (coronary artery bypass grafting [CABG] or percutaneous coronary intervention
      [PCI]) in patients with vascular disease. METHODS: Four hundred fifty-nine
      patients underwent risk stratification (high, intermediate, low) before 534
      consecutive elective or urgent (<24 hours after presentation) open
      cerebrovascular, aortic, or lower limb reconstruction procedures between August
      1996 and January 2000. Long-term follow-up (mean, 56 +/- 14 months) was possible
      in 97% of patients. The Kaplan-Meier method was used for survival data. Long-term
      prognostic variables were identified with the multivariate Cox proportional
      hazards model and contingency table analysis censoring early (<30 days)
      perioperative deaths. RESULTS: While 5-year survival was 72% for the overall
      cohort, cardiac causes accounted for only 24% of all deaths, and new cardiac
      events (myocardial infarction, congestive heart failure, arrhythmia, unstable
      angina, new coronary angiography, new CABG or PCI, cardiac death) affected only
      4.6% of patients per year during follow-up. High cardiac risk stratification
      level (hazards ratio [HR], 2.2, 95% confidence interval [CI], 1.4-3.4), adverse
      perioperative cardiac events (myocardial infarction, congestive heart failure,
      ventricular arrhythmia; HR, 2.2; 95% CI, 1.2-4.1), and age (HR, 0.33; 95% CI, 0.2
      0.6) were independently prognostic for latemortality. Preoperative cardiac risk
      levels also correlated with new cardiac event rates ( P < .01) and late cardiac
      mortality ( P = .02). Modestly improved survival in patients who had undergone
      CABG or PCI less than 5 years before vascular operations compared with those who
      had undergone revascularization 5 or more years previously and those at high risk
      without previous coronary intervention (73% vs 58% vs 62% 5-year survival; P =
      .02) could be demonstrated with univariate testing, but not with multivariate
      analysis. Type of operation, urgency, noncardiac complications, and presence of
      diabetes did not affect long-term survival. CONCLUSION: Despite cardiac events
      being a less common cause of late mortality after vascular surgery, perioperative
      cardiac factors (age, preoperative risk level, early cardiac complications) are
      the primary determinants of patient longevity. Patients undergoing more recent
      (<5 years) CABG or PCI before vascular surgery do not have an obvious survival
      advantage compared with patients at high cardiac risk without previous coronary
      interventions.

PMID- 15472606
TI  - Diabetes as an independent risk factor for early postoperative complications in
      critical limb ischemia.
AB  - OBJECTIVE: The purpose of this study was to evaluate the significance of diabetes
      mellitus as a risk factor for postoperative major morbidity and mortality after
      surgery for critical lower limb ischemia (CLI). SUBJECTS: A national vascular
      registry (Finnvasc)-based survey included 5709 operations for CLI from 1991
      through 1999. Of these operations, 2508 (44%) were performed on diabetics. Tissue
      loss was the indication for surgery in 77% of diabetics and in 52% of
      nondiabetics. The proportion of femorodistal bypasses was 43% in diabetics and
      24% in nondiabetics, whereas the proportion of reconstructions for aortofemoral
      arterial occlusive disease was 16% in diabetics and 34% in nondiabetics. RESULTS:
      Thirty-day mortality was 4.5% in diabetics and 3.4% in nondiabetics ( P = .05).
      The rate for early below-knee amputation was 6.5% in diabetics and 3.3% in
      nondiabetics ( P < .001). Independent factors for postoperative death were
      aortofemoral reconstruction (odds ratio [OR], 4.0), preoperative cardiac risk
      factor (OR, 3.1), primary surgery (OR, 2.0), renal insufficiency (OR, 1.9),
      urgent surgery (OR, 1.7), and age (OR, 1.3). Diabetes was an independent risk
      factor for postoperative below-knee amputation (OR, 1.7), cardiac complications
      (OR, 1.5), and superficial wound infection (OR, 1.3). There was an inverse
      association between diabetes and acute graft occlusion (OR, 0.8). Independent
      risk factors for early postoperative mortality in diabetes were aortofemoral
      reconstruction (OR, 2.5), urgent surgery (OR, 2.0), male gender (OR, 2.0), renal
      insufficiency (OR, 1.9), cardiac risk factor (OR, 1.7), and age (OR, 1.4). In
      nondiabetics independent risk factors for early postoperative mortality were
      aortofemoral reconstruction (OR, 4.5), cardiac risk factor (OR, 3.6), primary
      surgery (OR, 2.6), and extra-anatomic bypass (OR, 2.3). CONCLUSIONS: Diabetes was
      not an independent risk factor for early postoperative mortality in CLI as there
      was an increased morbidity in diabetics associated with old age, male gender,
      known coronary artery disease, and renal insufficiency, as well as urgent
      surgery. As diabetics have increased proclivity for these factors, special
      attention needs to be paid to their preoperative assessments.

PMID- 15472607
TI  - Serum total 8-iso-prostaglandin F2alpha: a new and independent predictor of
      peripheral arterial disease.
AB  - OBJECTIVE: Circulating 8-iso-prostaglandin F 2alpha (8-iso-PGF 2alpha ) has been
      proposed as new indicator of oxidative stress, which is involved in the
      pathophysiologic changes of atherosclerosis. We proposed to test the hypothesis
      that 8-iso-PGF 2alpha is an independent predictor of symptomatic peripheral
      arterial disease (PAD). METHODS: A case-control study in 100 patients with
      symptomatic PAD and 100 control subjects matched for age, sex, and diabetes
      mellitus was conducted. Smokers and subjects using lipid-lowering drugs were
      excluded. Serum total 8-iso-PGF 2alpha was quantified with an enzyme immunoassay.
      RESULTS: Median 8-iso-PGF 2alpha was higher in patients with PAD than in control
      subjects (63 vs 42 pg/mL; P = .001). Logistic regression with hypertension, body
      mass index, and creatinine, low-density lipoprotein (LDL) cholesterol,
      triglyceride, high-sensitivity C-reactive protein (hs-CRP), 8-iso-PGF 2alpha ,
      and total homocysteine concentrations as independent variables and case-control
      status as dependent variable revealed significant odds ratios (OR) for
      hypertension (OR, 3.74; 95% confidence interval [CI], 1.85-7.53), low-density
      lipoprotein cholesterol (OR, 1.16, for an increment of 10 mg/dL; 95% CI, 1.07
      1.27), high-sensitivity C-reactive protein (OR, 1.02, for an increment of 1 mg/L;
      95% CI, 1.00-1.03), and 8-iso-PGF 2alpha (OR, 1.11, for an increment of 10 pg/mL;
      95% CI, 1.03-1.20). CONCLUSIONS: Serum total 8-iso-PGF 2alpha was an independent
      predictor of PAD in the population studied. This finding supports the hypothesis
      that 8-iso-PGF 2alpha is a risk marker for PAD. Our results indicate increased
      systemic oxidative stress in patients with PAD.

PMID- 15472608
TI  - Autologous skeletal myoblasts transduced with a new adenoviral bicistronic vector
      for treatment of hind limb ischemia.
AB  - OBJECTIVE: We aimed to achieve angiogenic synergism between human vascular
      endothelial growth factor 165 (VEGF 165 ) and angiopoietin-1 (Ang-1) using a new
      adenoviral bicistronic vector concurrently with cell therapy to repair an
      ischemically damaged hind limb in a rabbit model. METHODS: Rabbit autologous
      primary skeletal myoblasts were isolated and labeled with retrovirally transduced
      LacZreporter gene, 4,6-diamidino-2-phenylindole (DAPI), and 5-bromo-2'
      deoxyuridine (BrdU). Hind limb ischemia was created in 48 female New Zealand
      White rabbits by means of femoral artery ligation at 8 different places, and was
      assessed at angiography. Animals were randomized to receive intramuscular
      injection of either Dulbeco's Modified Eagle Medium (DMEM;group 1, n = 8),
      nontransduced myoblasts (group 2, n = 10), or myoblasts transduced with Ad-Null
      (group 3, n = 10), Ad-VEGF (group 4, n = 10), or Ad-Bicis (group 5, n = 8). Six
      weeks after treatment neovascularization in the limb was assessed at angiography.
      The animals were euthanized, and tissue was harvested for histologic study.
      RESULTS: Extensive transplanted myoblast survival was observed in all cell
      transplanted groups, as visualized with DAPI, BrdU, and LacZ staining.
      Angiographic blood vessel count revealed enhanced neovascularization in group 5
      (25.14 +/- 5.14) compared with group 4 (13.62 +/- 4.52), group 3 (6.09 +/- 0.09),
      group 2 (4.67 +/- 3.49), and group 1 (3.18 +/- 7.76). Immunostaining for von
      Willebrand factor confirmed significantly increased capillary density ( P < .01)
      at high-power microscopic field in group 5 (19.04 +/- 1.59) compared with group 4
      (15.31 +/- 1.55), group 3 (6.53 +/- 0.97), group 2 (5.69 +/- 0.51), and group 1
      (3.03 +/- 0.20). CONCLUSION: Simultaneous expression of VEGF and Ang-1 from
      bicistronic vector transduced skeletal myoblasts potently stimulated enhanced
      functional neovascularization in a rabbit model of limb ischemia.

PMID- 15472609
TI  - CCR2-/- knockout mice revascularize normally in response to severe hindlimb
      ischemia.
AB  - OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1) is reported to stimulate
      ischemia-induced arteriogenesis (collateral artery development) by recruiting
      monocytes and macrophages into areas of active arteriogenesis. To determine
      whether the MCP-1-mediated response occurs through its receptor, CC-chemokine
      receptor 2 (CCR2), we induced hindlimb ischemia in mice lacking the receptor for
      MCP-1 (CCR2 -/- ) and measured limb blood flow recovery, collateral artery
      development, and monocyte and macrophage recruitment. METHODS AND RESULTS:
      Hindlimb ischemia was induced by excising the left femoral artery in CCR2 -/- and
      wild-type mice. Hindlimb blood flow recovery, as measured using laser Doppler
      perfusion imaging, was equivalent in both groups ( P = .78 for foot and P = 0.38
      for calf). Collateral artery development, as measured by angiography at
      postoperative day 14 and 31, likewise did not differ between the 2 groups ( P =
      .46 and P = .67). Counts of monocytes and macrophages in calf and thigh muscle
      sections of mice sacrificed on postoperative day 7 revealed that although CCR2 -/
      mice recruited 44% fewer monocytes and macrophages to areas of ischemia in the
      calf, they recruited similar numbers of monocytes and macrophages to areas of
      active arteriogenesis in the thigh. Intercellular adhesion molecule-1 and MCP-1
      mRNA levels were higher in the thigh muscle of CCR2 -/- mice than in wild-type
      mice (5.5-fold and 42.3-fold induction operated to unoperated vs 2.6-fold and 6.1
      fold induction operated to unoperated, respectively). CONCLUSIONS: Blood flow
      recovery, arteriogenesis, and monocyte and macrophage recruitment to the thigh
      was normal in CCR2 -/- mice. However, monocyte and macrophage recruitment to the
      ischemic calf was diminished in CCR2 -/- mice. Our results show that MCP-1
      signaling through CCR2 is not required for physiologic arteriogenesis in response
      to severe hindlimb ischemia. ICAM-1 upregulation may substitute for MCP-1
      signaling through CCR2 in order to allow normal arteriogenesis in CCR2 -/- mice.

PMID- 15472610
TI  - Plasma homocysteine measurements after carotid artery manipulation and clamping
      in a rat CEA model.
AB  - OBJECTIVE: The effect of a rat carotid endarterectomy (CEA) on homocysteine and
      the metabolic enzymes methylenetetrahydrofolate reductase (MTHFR) and
      cystathionine beta-synthase (CBS) was studied. METHODS: Rats were placed into 7
      groups: (1) no anesthesia (NA), (2) anesthesia only (AO), (3) skin opened and
      closed (O/C), (4) skin opened with exposure of the carotid artery and closed
      (O/E/C), (5) carotid isolated and clamped (CO), (6) open CEA, and (7) open
      femoral endarterectomy (FEA). End points included homocysteine, hepatic MTHFR,
      and CBS activity. RESULTS: Homocysteine in the NA, AO, O/C, O/E/C, and FEA were
      low and not different. CEA produced a 6-fold increase in homocysteine when
      compared with non-CEA groups. Specifically, CEA produced an increase in
      homocysteine versus the AO group at 2 weeks (11.3 +/- 0.7 vs 2.1 +/- 0.9
      micromol/L;P < .001), 4 weeks (8.9 +/- 0.7 vs 3.5 +/- 0.9 micromol/L; P = .004)
      and 6 weeks (7.7 +/- 0.9 vs 3.1 +/- 1.5 micromol/L; P = .03). The CO group had
      increased homocysteine versus the O/C, O/E/C, and FEA, but was lower than the CEA
      group. CEA produced an increase in MTHFR and CBS versus the AO group.
      CONCLUSIONS: CEA resulted in elevated levels of homocysteine; however, when
      broken down into its component parts, no elevation was observed except for a
      small increase with the CO procedure. Manipulation of the femoral artery did not
      raise homocysteine levels. The increase in homocysteine is possibly due to the
      combination of vessel wall damage and changes in cerebral blood flow dynamics.

PMID- 15472611
TI  - Nitric oxide-releasing biopolymers inhibit thrombus formation in a sheep model of
      arteriovenous bridge grafts.
AB  - OBJECTIVES: Nitric oxide (NO), produced by normal vascular endothelial cells,
      reduces platelet aggregation and thrombus formation. NO-releasing biopolymers
      have the potential to prolong vascular graft and stent patency without adverse
      systemic vasodilation. METHODS: 5-mm polyurethane vascular grafts coated with a
      polymer containing the NO-donor dialkylhexanediamine diazeniumdiolate were
      implanted for 21 days in a sheep arteriovenous bridge-graft model. RESULTS:
      Eighty percent (4/5) of grafts coated with the NO-releasing polymer remained
      patent through the 21 day implantation period, compared to fifty percent (2/4) of
      sham-coated grafts and no (0/3) uncoated grafts. Thrombus-free surface area (+/
      SEM) of explanted grafts was significantly increased in NO-donor coated grafts
      (98.2% +/- 0.9%) compared with sham-coated (79.2% +/- 8.6%) and uncoated (47.2%
      +/- 5.4%) grafts ( P = .00046). Examination of the graft surface showed no
      adherent thrombus or platelets and no inflammatory cell infiltration in NO-donor
      coated grafts, while control grafts showed adherent complex surface thrombus
      consisting of red blood cells in an amorphous fibrin matrix, as well as
      significant red blood cell and inflammatory cell infiltration into the graft
      wall. CONCLUSION: In this study we determined that local NO release from the
      luminal surface of prosthetic vascular grafts can reduce thrombus formation and
      prolong patency in a model of prosthetic arteriovenous bridge grafts in adult
      sheep. These findings may translate into improved function and improved primary
      patency rates in small-diameter prosthetic vascular grafts.

PMID- 15472612
TI  - Masson's intravascular hemangioma masquerading as effort thrombosis.
AB  - An otherwise healthy 55-year-old white woman had acute onset of right arm
      swelling. No precipitating factors were identified. Venograms revealed an
      occluded subclavian vein, and catheter-directed thrombolysis was performed. After
      lysis a persistent residual intraluminal filling defect was identified, with
      persistent symptoms. Partial claviculectomy was performed, the mass was removed,
      and patch venoplasty carried out, with good outcome. Pathologic analysis
      demonstrated the mass to be a Masson's hemangioma, a papillary proliferation of
      thin-walled capillaries intimately associated with thrombus. Considered a benign
      intravascular lesion, the treatment of choice is complete excision.

PMID- 15472613
TI  - Diaphragm-like membrane causing common femoral vein obstruction: case report.
AB  - A 23-year-old woman had exercise-induced right leg symptoms. An extensive
      diagnostic workup including 2 surgical explorations was performed, but did not
      reveal the cause. Finally, high-resolution color-coded duplex scanning was
      performed, which demonstrated an isolated, nonthrombotic obstruction of the
      common femoral vein by a diaphragm-like membrane. Successful operative repair was
      accomplished with venotomy and excision of the membrane, with full relief from
      clinical signs and symptoms at 9-month follow-up.

PMID- 15472614
TI  - Unilateral lower extremity paralysis after coil embolization of an internal iliac
      artery aneurysm.
AB  - Neurologic complications after treatment of internal iliac artery (IIA) aneurysms
      are rare, especially if confined to one IIA. We report a patient in whom profound
      right lower extremity paresis developed after unilateral right IIA coil
      embolization for treatment of a 4-cm IIA aneurysm, despite the presence of a
      patent contralateral IIA. This case illustrates the important, yet unpredictable,
      nature of pelvic blood flow to the distal spinal cord and lumbosacral plexus and
      the unpredictable consequence of IIA occlusion.

PMID- 15472615
TI  - Total laparoscopic repeat aortic surgery.
AB  - We report our initial experience with total laparoscopic repeat aortic surgery
      between June 2002 and October 2003. There were 4 patients, 3 men and 1 woman,
      ages 83, 67, 49, and 61 years, respectively. First operations were performed to
      treat aortoiliac occlusive disease. Repeat aortic surgery was indicated to treat
      para-anastomotic aneurysms (n = 2) and graft occlusion (n = 2). All patients
      underwent total laparoscopic surgery. There were no postoperative deaths. Only 1
      patient had postoperative complications that required complementary surgical
      treatment. All patients were alive with patent revascularization after a mean
      follow-up of 14, 17, 20, and 12 months, respectively.

PMID- 15472616
TI  - Aortobifemoral graft infection with Mycobacterium tuberculosis: treatment with
      abscess drainage, debridement, and long-term administration of antibiotic agents.
AB  - Aortic graft infection with Mycobacterium tuberculosis is rare. We report a
      patient with a Dacron aortobifemoral prosthetic graft infection secondary to
      tuberculosis. The infection was successfully treated with surgical drainage
      without removal of the graft, and long-term antimycobacterial medications. A
      review of the literature contains only 1 other report of tuberculosis graft
      infection and treatment. We discuss a rare form of aortic graft infection from M
      tuberculosis and its treatment.

PMID- 15472617
TI  - Primary popliteal venous aneurysm.

PMID- 15472618
TI  - Family-surgeon disagreements over interventions.

PMID- 15472627
TI  - Regarding "withdrawal of article by the FDA after objection from Medtronic".

PMID- 15472628
TI  - Regarding "caution in signing nondisclosure contracts".

PMID- 15472630
TI  - Regarding 'ethics of boutique medical practice'.

PMID- 15472631
TI  - Regarding "standards of practice: carotid angioplasty and stenting".

PMID- 15472634
TI  - Call for a mandatory national clinical trials registry.

PMID- 15472635
TI  - Prolonged myocardial stunning with adenosine infusion on gated SPECT imaging.

PMID- 15472636
TI  - Factors influencing predictive value of FDG imaging for evaluating myocardial
      viability.

PMID- 15472637
TI  - Incidence and predictors of heart failure during long-term follow-up after stress
      Tc-99m sestamibi tomography in patients with suspected coronary artery disease.
AB  - BACKGROUND: Heart failure is a major cause of morbidity and death in patients
      with coronary artery disease (CAD). The aim of this study was to define the
      incidence and predictors of heart failure during long-term follow-up in patients
      with suspected CAD referred for stress myocardial perfusion imaging. METHODS AND
      RESULTS: We studied 787 patients (mean age, 57 +/- 12 years; 470 men) with
      suspected CAD who had no history of previous myocardial infarction or heart
      failure with exercise (n = 508) or dobutamine (n = 279) stress technetium 99m
      sestamibi single photon emission computed tomography. Patients were followed up
      for the occurrence of heart failure, nonfatal myocardial infarction, and death.
      An abnormal perfusion scan (reversible or fixed perfusion defect) was detected in
      341 patients (43%). During a mean follow-up of 6.7 +/- 2.3 years, heart failure
      occurred in 46 patients (6%), 170 patients (22%) died, and 52 patients (7%) had
      nonfatal myocardial infarction. Patients in whom heart failure developed were
      older (mean age, 60 +/- 12 years vs 56 +/- 12 years; P = .01) and were more
      likely to be men (34 [74%] vs 436 [59%], P = .01) and to have an abnormal scan
      (32 [70%] vs 309 [42%], P = .0002) compared with patients without heart failure.
      Nonfatal myocardial infarction occurred before the onset of heart failure in only
      3 patients (7%). By multivariate analysis, predictors of heart failure were age
      (risk ratio [RR], 1.04 [95% CI, 1.01-1.08]), male gender (RR, 2 [95% CI, 1.3
      4.5]), resting heart rate (RR, 1.1 [95% CI, 1.05-1.2]), and abnormal scan (RR,
      2.3 [95% CI, 1.4-3.9]). The annual mortality rate was 15% after the diagnosis of
      heart failure. CONCLUSION: In patients with suspected CAD and no history of
      myocardial infarction, late heart failure is predicted by age, gender, resting
      heart rate, and abnormal perfusion, and it is associated with a substantial
      mortality rate. The majority of heart failure events are heralded by perfusion
      abnormalities on sestamibi single photon emission computed tomography but not by
      an earlier myocardial infarction.

PMID- 15472638
TI  - Postischemic stunning after adenosine vasodilator stress.
AB  - BACKGROUND: Ischemic left ventricular (LV) dysfunction may occur after exercise
      but is regarded as uncommon after vasodilator stress. We evaluated the prevalence
      of LV dysfunction after adenosine stress in relation to reversible perfusion
      defects and angiographic coronary artery disease (CAD). METHODS AND RESULTS: We
      studied 86 patients referred for clinically indicated adenosine dual-isotope
      gated single photon emission computed tomography: 43 with 1 or more reversible
      perfusion defects (reversible defect group) and 43 age- and sex-matched patients
      with no known CAD and normal LV perfusion and function (control group). Coronary
      angiography was performed in 36 of 43 patients (84%) in the reversible defect
      group. Perfusion was interpreted based on 20-segment/5-point summed rest and
      stress scores. The extent of reversibility was defined by the summed difference
      score. LV ejection fraction and volumes at rest and 60 minutes after adenosine
      and segmental wall thickening were quantified by QGS (Cedars-Sinai Medical
      Center, Los Angeles, Calif). In patients with extensive reversible perfusion
      defects (summed difference score > or =8), 8 of 25 (32%) demonstrated depressed
      post-adenosine LV ejection fraction, abnormal segmental wall thickening, end
      systolic dilation, and extensive CAD. CONCLUSION: Adenosine is believed to be
      less likely than exercise to induce ischemia. However, myocardial stunning
      occurred in one third of the patients with severe reversible defects, consistent
      with ischemia.

PMID- 15472639
TI  - Incremental prognostic value of left ventricular function by myocardial ECG-gated
      FDG PET imaging in patients with ischemic cardiomyopathy.
AB  - BACKGROUND: The purpose of this study was to determine the independent value of
      left ventricular (LV) functional parameters derived from gated fluorine 18
      fluorodeoxyglucose (FDG) positron emission tomography (PET) to predict prognosis
      in patients with ischemic cardiomyopathy undergoing myocardial viability
      assessment. METHODS AND RESULTS: We studied 90 consecutive patients with coronary
      artery disease and low LV ejection fraction (26% +/- 7%) undergoing gated FDG PET
      to assess myocardial viability for potential revascularization. The primary
      endpoint for this analysis was the occurrence of cardiac death, myocardial
      infarction, or worsening heart failure (HF) to New York Heart Association class
      IV. During follow-up (22 +/- 14 months), 21 patients had an event (17 died, 4 had
      myocardial infarctions, and 4 had worsening HF). On Cox regression analysis, the
      event-free survival rate at 2 years was lower for patients with an end-diastolic
      volume (EDV) of 260 mL or greater (relative risk, 2.7; P = .014), end-systolic
      volume (ESV) of 200 mL or greater (relative risk, 2.5; P = .021), and LV mass of
      143 g or greater (relative risk, 1.6; P = .009). In a risk-adjusted model, EDV
      (chi 2 = 68, P < .0001) and ESV (chi 2 = 75, P = .035) added a significant amount
      in the estimation of events over the perfusion-FDG mismatch pattern (chi 2 = 40,
      P < .001). In a stratified Cox model, patients with PET mismatch, LV ejection
      fraction lower than 25%, and EDV of 260 mL or greater had the lowest survival
      rate (P = .006). These patients showed an apparent survival benefit with
      revascularization but without an improvement in HF symptoms. CONCLUSION: LV
      functional parameters determined by gated FDG PET have incremental prognostic
      value over viability information in patients with ischemic cardiomyopathy. Our
      data suggest that patients with residual viability and advanced cardiac
      remodeling are at high clinical risk. In these patients the apparent survival
      benefit of revascularization may not be associated with a measurable improvement
      in HF symptoms.

PMID- 15472640
TI  - Comparison of risk stratification with pharmacologic and exercise stress
      myocardial perfusion imaging: a meta-analysis.
AB  - BACKGROUND: Although pharmacologic stress myocardial perfusion imaging (MPI) and
      exercise stress MPI have comparable diagnostic accuracy, their comparative value
      for risk stratification of patients with known or suspected coronary disease is
      not known. METHODS AND RESULTS: The data of 14,918 patients were combined from 24
      studies evaluating prognosis in patients undergoing either pharmacologic stress
      or exercise stress MPI. Studies were included if a 2 x 2 table for hard cardiac
      events (cardiac death and myocardial infarction [MI]) could be constructed from
      the data available. Excluded were studies performed for post-MI, post
      revascularization, or preoperative risk stratification. A weighted t test was
      used to compare the cardiac events, and a random effects model was used to
      calculate summary odds ratios. Summary odds ratios for hard cardiac events were
      similar for pharmacologic stress and exercise stress MPI. Summary receiver
      operating characteristic curves also showed no difference in discriminatory power
      between the stressors. The cardiac event rates were significantly higher with
      normal and abnormal test results with pharmacologic stress MPI than with exercise
      stress MPI (1.78% vs 0.65% [P < .001] for normal results and 9.98% vs 4.3% [P <
      .001] for abnormal results). Subgroup analysis revealed that both cardiac death
      and nonfatal MI were significantly higher with pharmacologic stress MPI. Patients
      undergoing pharmacologic stress MPI had a significantly higher prevalence of poor
      prognostic factors, and meta-regression revealed that exercise capacity was the
      single most important predictor of cardiac events. CONCLUSIONS: This meta
      analysis shows that exercise stress MPI and pharmacologic stress MPI are
      comparable in their ability to risk-stratify patients. However, patients
      undergoing pharmacologic stress studies are at a higher risk for subsequent
      cardiac events. This is true even for those with normal perfusion imaging
      results.

PMID- 15472641
TI  - Noninvasive assessment of coronary microvascular dysfunction using Tc-99m
      tetrofosmin SPECT in patients with acute myocardial infarction.
AB  - BACKGROUND: We investigated whether technetium 99m tetrofosmin (TF) single photon
      emission computed tomography (SPECT) could predict coronary microvascular
      dysfunction in patients with acute myocardial infarction. METHODS AND RESULTS: We
      obtained the regional severity score index (TF-RSSI) using TF SPECT immediately
      after percutaneous coronary intervention in 25 patients with acute myocardial
      infarction. Using a Doppler guidewire, we evaluated the deceleration time of
      diastolic flow velocity (DDT) after percutaneous coronary intervention, and DDT
      of 600 milliseconds or less was suggested to be an indicator of coronary
      microvascular dysfunction. Moreover, the chronic regional wall motion score index
      (RWMSI) was obtained from echocardiography during the chronic phase. There was a
      good correlation between TF-RSSI and DDT (r = -0.68, P < .01). The optimal cutoff
      value of TF-RSSI to predict DDT of 600 milliseconds or less was defined as 1.9 or
      greater (sensitivity, 1.00; specificity, 0.71). The group with poor scintigraphic
      coronary microvascular function (TF-RSSI > or =1.9, n = 7) demonstrated a
      significantly shorter DDT (P = .0003), a lower frequency of early systolic
      retrograde flow (P = .0038), and greater chronic RWMSI (P = .0015) than the group
      with good scintigraphic coronary microvascular function (TF-RSSI <1.9, n = 15).
      CONCLUSIONS: Analysis of TF SPECT immediately after percutaneous coronary
      intervention in patients with acute myocardial infarction is a useful noninvasive
      method for evaluating coronary microvascular dysfunction.

PMID- 15472642
TI  - Acute resting myocardial perfusion imaging in patients with diabetes mellitus:
      results from the Emergency Room Assessment of Sestamibi for Evaluation of Chest
      Pain (ERASE Chest Pain) trial.
AB  - BACKGROUND: Resting myocardial perfusion imaging (MPI) improves the triage of
      patients presenting to the emergency department (ED) with symptoms suggestive of
      acute cardiac ischemia (ACI). In the ED setting the presence of diabetes mellitus
      (DM) is a predictor of ACI and hospitalization, but the role of resting MPI in
      patients with DM is unknown. METHODS AND RESULTS: A secondary data analysis of a
      prospective, multicenter, randomized, controlled trial of ED evaluation
      strategies in patients with symptoms suggestive of ACI and normal or
      nondiagnostic electrocardiograms was performed. In the main trial 2475 patients
      were randomized to receive either the usual ED evaluation strategy (n = 1260) or
      the usual strategy supplemented by results from resting MPI by use of single
      photon emission computed tomography (SPECT) technetium 99m sestamibi (n = 1215).
      Patients with diabetes (n = 341) were evaluated separately. Imaging results,
      final diagnoses, effect on triage, and prognostic value of the SPECT imaging were
      compared between diabetic and nondiabetic patients. Of the 341 patients with
      diabetes, 153 (45%) were randomized to the imaging strategy. Patients with DM had
      higher rates of hospitalization (66% vs 49.6%, P = .0001) and ACI (21.1% vs
      12.0%, P < .001) than patients without DM. Among diabetic patients without ACI,
      the admission rate was 63% in the usual strategy group versus 54% in the imaging
      strategy group (relative risk [RR] = 0.91 [95% CI, 0.76-1.06]; P = .24). There
      was no difference in the magnitude of this reduced risk of admission compared
      with patients without DM (RR = 0.84 [95% CI, 0.77-0.92]; P = .0002 for patients
      without DM and P = .35 for interaction of diabetes and RR reduction).
      CONCLUSIONS: Acute resting MPI with Tc-99m sestamibi is associated with improved
      triage decision making in symptomatic ED patients with diabetes.

PMID- 15472643
TI  - Do myocardial perfusion SPECT and radionuclide angiography studies in adult
      patients with hypertrophic cardiomyopathy have prognostic implications?
AB  - BACKGROUND: Some myocardial perfusion single photon emission computed tomography
      (SPECT) and radionuclide ventriculography studies have suggested that the
      presence of regional perfusion defects and diastolic abnormalities could have
      prognostic implications in patients with hypertrophic cardiomyopathy (HC). The
      aim of this prospective study was to analyze the prognostic value of these
      techniques in adult patients with HC. METHODS AND RESULTS: One hundred one
      patients with HC (44 women; mean age, 54 +/- 16 years; 55% obstructive) were
      prospectively studied by means of myocardial perfusion SPECT and radionuclide
      angiography. Of these patients, 55 (54.4%) had an abnormal myocardial perfusion
      SPECT study: 28 (27.7%) had fixed defects and 41 (40.6%) had reversible defects;
      15 (14.8%) of these patients had both types of defect. Of the patients, 16% had
      left ventricular ejection fraction lower than 60%, 25.7% had an abnormal peak
      filling rate, and 51% had an abnormal time to peak filling rate. During 5.6 +/-
      2.7 years of follow-up, 13 patients (12.8%) died (heart failure 8 and sudden
      death in 5) and 14 had one or more severe complications develop (syncope in 6,
      angina III-IV in 4, dyspnea III-IV in 10, and acute myocardial infarction in 3).
      The summed difference score was higher in patients with cardiac death (2.2 +/-
      2.3 vs 1.1 +/- 1.3, P = .008), and fixed defects were more prevalent in patients
      with severe complications (57% vs 21%, P = .01). In the Kaplan-Meier survival
      plot analysis, severe complications were more likely in patients with fixed
      defects (P = .01) or ejection fraction lower than 60% ( P = .01). CONCLUSIONS:
      Prognostic information from myocardial perfusion SPECT and radionuclide
      angiography has limited clinical significance with regard to cardiac death in
      adult patients with HC. However, the presence of fixed defects and lower ejection
      fraction in these patients has an adverse prognostic meaning for severe
      complications.

PMID- 15472644
TI  - Cardiac neurotransmission SPECT imaging.
AB  - The sympathetic nervous system has great influence on cardiovascular physiology.
      Cardiac neurotransmission single photon emission computed tomography (SPECT)
      imaging allows in vivo noninvasive assessment of presynaptic reuptake and storage
      of neurotransmitters, which offers characterization of the cardiac neuronal
      function in different diseases of the heart and other altered metabolic or
      functional conditions. Therefore assessment of the integrity of cardiac
      sympathetic innervation may help in the diagnosis of these disorders, as well as
      in prognostication, and will result in better therapy and outcome. At present,
      the most widely available SPECT tracer by which to assess cardiac
      neurotransmission is metaiodobenzylguanidine labeled with iodine 123. This
      article focuses on reviewing the characteristics of cardiac SPECT imaging with I
      123 metaiodobenzylguanidine and its role in the assessment of pathophysiologic
      changes during relevant clinical conditions.

PMID- 15472645
TI  - Assessment of cardiac sympathetic neuronal function using PET imaging.
AB  - The autonomic nervous system plays a key role for regulation of cardiac
      performance, and the importance of alterations of innervation in the
      pathophysiology of various heart diseases has been increasingly emphasized.
      Nuclear imaging techniques have been established that allow for global and
      regional investigation of the myocardial nervous system. The guanethidine analog
      iodine 123 metaiodobenzylguanidine (MIBG) has been introduced for scintigraphic
      mapping of presynaptic sympathetic innervation and is available today for imaging
      on a broad clinical basis. Not much later than MIBG, positron emission tomography
      (PET) has also been established for characterizing the cardiac autonomic nervous
      system. Although PET is methodologically demanding and less widely available, it
      provides substantial advantages. High spatial and temporal resolution along with
      routinely available attenuation correction allows for detailed definition of
      tracer kinetics and makes noninvasive absolute quantification a reality.
      Furthermore, a series of different radiolabeled catecholamines, catecholamine
      analogs, and receptor ligands are available. Those are often more physiologic
      than MIBG and well understood with regard to their tracer physiologic properties.
      PET imaging of sympathetic neuronal function has been successfully applied to
      gain mechanistic insights into myocardial biology and pathology. Available
      tracers allow dissection of processes of presynaptic and postsynaptic innervation
      contributing to cardiovascular disease. This review summarizes characteristics of
      currently available PET tracers for cardiac neuroimaging along with the major
      findings derived from their application in health and disease.

PMID- 15472647
TI  - SPECT perfusion abnormalities in patients with noncompacted myocardium: a
      comparative image with cardiac magnetic resonance.

PMID- 15472646
TI  - Imaging of angiogenesis.

PMID- 15472653
TI  - The clinical significance of anaerobic bacteria in acute orofacial odontogenic
      infections.
AB  - A review of the literature on orofacial odontogenic infections indicates that the
      underlying microflora is typically polymicrobial, predominantly involving
      strictly anaerobic gram-positive cocci and gram-negative rods, along with
      facultative and microaerophilic streptococci. Although no single species has been
      consistently implicated in all of these infections, the pathogenic potential of
      some of these organisms has been documented by many studies. This potential can
      be explained by a number of virulence factors demonstrated in anaerobic bacteria,
      as well as by synergistic interrelationships with other members of the infectious
      flora. Awareness of the anaerobic component of orofacial odontogenic infections
      dictates to a large extent the selection of antimicrobial therapy, mainly because
      of the frequency of beta-lactamase production by anaerobic gram-negative rods.

PMID- 15472652
TI  - A randomized controlled trial of resorbable versus titanium fixation for
      orthognathic surgery.
AB  - OBJECTIVES: To determine any differences in the intra- and postoperative
      morbidities and complications between resorbable and titanium plating systems for
      fixation in orthognathic surgery. STUDY DESIGN: This prospective randomized
      clinical trial was conducted in the Oral and Maxillofacial Surgery unit of the
      University of Hong Kong. Patients with dentofacial deformities were randomly
      assigned into the titanium and resorbable fixation groups. Intraoperative data
      such as the surgical procedures, time for fixing each plate, and number of broken
      plates and screws were recorded. Subjective and objective parameters related to
      clinical morbidities were assessed postoperatively. RESULTS: A total of 60
      patients with 177 osteotomies were included in this study. Eighty-seven
      osteotomies fixated with 196 titanium plates and 784 titanium screws were
      performed in 30 patients, whereas 90 osteotomies fixated with 165 resorbable
      plates and 658 resorbable screws were done in another 30. The postoperative
      infection rate was 1.53% (3/196) and 1.82% (3/165) in the titanium and resorbable
      fixation groups, respectively. These infections were mainly due to loose screws
      and wound dehiscence. The plate exposure rate was 1.02% (2/196) for the titanium
      group and 1.21% (2/165) for the resorbable group. The plate removal rate in the
      titanium and resorbable groups was 1.53% (3/196) and 3.63% (6/165), respectively.
      Statistically significant difference was shown in the plating time of step
      (mandibular body) and Hofer (mandibular subapical) osteotomies. There was no
      significant difference in the subjective clinical parameters such as wound
      discomfort, clinical stability of the osteotomy segments, palpability of plate,
      and overall satisfaction of the results between the 2 fixation groups. Similarly,
      objective parameters including wound dehiscence, rate of infection, plate
      exposure, occurrence of sinus tract, and palpability assessed by surgeons in both
      groups also showed no significant difference. CONCLUSION: Bioresorbable fixation
      devices offer similar function as titanium in fixation for orthognathic surgery
      and do not impose an increase in the clinical morbidities.

PMID- 15472654
TI  - Primary hyperparathyroidism presenting as a palatal brown tumor.
AB  - Only 2% of all primary hyperparathyroidism cases occur in patients below the age
      of 30 years. Owing to the improved methods of blood analysis in the last 2
      decades, most of the recent cases of primary hyperparathyroidism are diagnosed
      early and asymptomatically. This makes advanced disease with bone lesions
      extremely rare these days. A case of a 25-year old female patient with previously
      undiagnosed primary hyperparathyroidism who presented first with palatal swelling
      is reported. Further investigations revealed parathyroid adenoma,
      nephrocalcinosis, and extensive bone lesions involving the maxillary sinus and
      palate as well as the pelvic bone. The evaluation of the hyperparathyroid patient
      is reviewed in this report. The methods of treatment of the bony lesions of
      primary hyperparathyroidism are also discussed.

PMID- 15472655
TI  - Two missense mutations in the IRF6 gene in two Japanese families with Van der
      Woude syndrome.
AB  - Van der Woude syndrome (VWS) is a common autosomal dominant disorder with cleft
      lip and/or palate and lower lip pits. Its prevalence is estimated to be 1/33,600
      in the Finnish Population, and 1/47,813 in the Japanese. We performed mutation
      analysis of the IRF6 gene by direct sequencing in 2 unrelated Japanese families
      that consist of a total of 3 affected members with cleft lip and palate
      associated with lower lip pits. Consequently, we found novel base substitutions,
      25C>T, in IRF6-exon 3 in a boy, his mother, and his phenotypically normal
      maternal grandmother in one of the families. A known mutation, 250C>T, was
      identified in exon 4 of a girl and her unaffected father in the other family. The
      same mutations were never observed among 190 healthy Japanese. The results
      indicate incomplete penetrance and variable expressivity in the families. Because
      25C>T and 250C>T predict to lead to R9W and R84C substitutions, respectively, at
      the most conserved DNA binding domain of IRF6, and because arginine at positions
      9 and 84 is highly conserved among IRFs, the 2 mutations may lead to abolish the
      DNA binding activity in the developing craniofacial region. To our knowledge,
      this is the first report of IRF6 mutations observed in Japanese VWS patients.

PMID- 15472656
TI  - Relationship between oral bacteria and hemodialysis access infection.
AB  - OBJECTIVE: Controversy exists concerning the association between oral bacteria
      and infection of hemodialysis (HD) shunts. The purpose of this study was to
      determine the extent to which oral bacteria are associated with vascular access
      site infections in a group of HD patients. STUDY DESIGN: Microbial blood culture
      data for 87 HD patients were collected: 53 via chart review (retrospective), and
      34 with newly suspected vascular access infections (prospective). The primary
      outcome was the nature (i.e., species) of the bacteria recovered from blood
      cultures of subjects with vascular access infection, specifically those bacteria
      considered to be oral flora. RESULTS: The predominant bacteria reported to cause
      HD vascular access infections were Staphylococcus (48.6%) and Enterococcus
      (17.6%) species. Most infections occurred in hemodialysis catheters (89%)
      compared with AV grafts (11%) and AV fistulas (0%). The subclavian venous access
      (41%) and the internal jugular venous access (38.9%) were more commonly infected
      than other sites. None of the bacteria identified by blood cultures were
      considered to be oral flora. CONCLUSION: The results suggest that oral bacteria
      rarely, if ever, cause vascular access infections in hemodialysis patients.

PMID- 15472657
TI  - A double-dummy, double-blind, placebo-controlled phase III study comparing the
      efficacy and efficiency of miconazole chewing gum with a known drug (Brentan gel)
      and a placebo in patients with oral candidosis.
AB  - OBJECTIVE: The purpose was to compare the therapeutic effect, the required
      overall treatment duration, and patients' subjective perception of treatment of
      candidosis with miconazole chewing gum 20 mg/piece (3.6 mg released) and 2%
      Brentan gel 2.5 g (50 mg released), both administered 4 times daily. STUDY
      DESIGN: Randomly selected patients (chewing gum: 96; gel: 28; placebo 16) were
      seen at baseline and at 4 and 6 weeks. They were evaluated clinically and with
      culture and cytology assays. RESULTS: There was no significant difference between
      the 2 drugs after 6 weeks, but miconazole released in small doses from chewing
      gum was at least as effective as a larger gel dose. Both active drugs
      demonstrated efficiency and efficacy (P=1.9%). The hypothesis of equal
      proportions was rejected (P=.0001). Patients preferred the chewing gum. There was
      a statistically significant difference in patient preference for the chewing gum
      treatment. CONCLUSION: The chewing gum medication is clinically promising.

PMID- 15472658
TI  - Abnormal oral vascular network geometric complexity in Ehlers-Danlos syndrome.
AB  - Ehlers-Danlos syndrome (EDS) leads to impaired extracellular matrix (ECM)
      structure. Since ECM plays a major role in blood vessel geometry, we tested the
      hypothesis of an abnormal geometrical complexity of the visible microvascular
      network in EDS. Twelve patients with EDS-II or EDS-III and a control population
      (n=12) were examined. The geometry characteristics for the networks on the lower
      vestibular oral mucosa were analyzed using high-resolution photographic images.
      Fractal dimension, D, at 2 scales (D 1-46 and D 1-15), blood vessel tortuosity
      (minimum-path fractal dimension , Dmin ), and relative Lempel-Ziv complexity (L
      Z) values were determined. EDS vascular networks exhibited significantly higher D
      1-46 (P <.00001) and D 1-15 (P <.00001), as well as L-Z complexity (P <.00001),
      together with lower Dmin values (P=.0001) than controls. These findings indicate
      the presence of a previously unrecognized microvascular network abnormality on
      the oral mucosa in EDS patients, and provide an additional phenotypical marker
      for the condition.

PMID- 15472659
TI  - Self-reported remission, difficulty, and satisfaction with nonsurgical therapy
      used to treat anterior disc displacement without reduction.
AB  - OBJECTIVE: The purpose of this study was to identify the appropriate treatment
      element for initial anterior disc displacement without reduction subjects. STUDY
      DESIGN: Sixty-nine consecutive patients with temporomandibular joint disc
      displacement without reduction confirmed on magnetic resonance images were
      randomly divided into 3 experimental treatment groups. The treatment of group 1
      consisted of short-term nonsteroidal anti-inflammatory drugs and self-care
      instructions (palliative care group); group 2, nonsteroidal anti-inflammatory
      drugs, self-care instructions, and occlusal appliance and mobilization therapy
      (physical medicine group); and group 3, no treatment (control group). Outcomes
      were assessed by means of a 5-item questionnaire that evaluated (1) symptom
      improvement, (2) difficulty of treatment, and (3) satisfaction with treatment
      during the 8-week observation period. RESULTS: Improvement scores in the
      palliative care group were significantly better than those in the physical
      medicine group or the no-treatment group. Satisfaction scores showed no
      significant difference among the 3 groups. Difficulty from treatment for the
      physical medicine group was significantly greater than that for other 2 groups.
      CONCLUSION: These data suggest that palliative care would be more appropriate as
      the initial therapy to treat painful anterior disc displacement without
      reduction.

PMID- 15472660
TI  - Lipoma of the oral and maxillofacial region: Site and subclassification of 125
      cases.
AB  - OBJECTIVE: Lipomas and lipoma variants are common soft tissue tumors, but occur
      infrequently in the oral and maxillofacial region. In this study, we reviewed 125
      lipomas in specific oral and maxillofacial locations. We wanted to examine and
      compare the clinicopathologic features of these tumors. Study design The records
      from the Oral and Maxillofacial Pathology Registry of the Armed Forces Institute
      of Pathology from 1970 to the present were searched for cases coded as "lipoma."
      This study included 125 cases based on location within the oral and maxillofacial
      region, benign histology, and available clinical information. Subcutaneous and
      intraosseous lipomas were excluded. The tumors were classified according to the
      most recent World Heath Organization classification for soft tissue tumors.
      RESULTS: Of 125 lipomas, 91 tumors occurred in males, 33 in female patients, and
      1 of unknown gender. The mean age was 51.9 years, range 9-92 years. Four tumors
      occurred in pediatric patients (age <18 years). Specific anatomic sites within
      the oral and maxillofacial region included the parotid region (n=30); buccal
      mucosa (n=29); lip (n=21); submandibular region (n=17); tongue (n=15); palate
      (n=6); floor of mouth (n=5); and vestibule (n=2). The mean size of tumors was 2.2
      centimeters, range 0.5 to 8.0 centimeters. The mean duration of the tumors prior
      to excision was 3.2 years, range 6 weeks to 15 years. Most patients presented
      with an asymptomatic, circumscribed mass. Grossly, most tumors were described as
      pink and smooth, occasionally mucoid. Histologically, the tumors were
      subclassified as classic lipomas (n=62); spindle cell/pleomorphic lipomas (n=59);
      fibrolipoma (n=2), and chondroid lipoma (n=2). Fourteen tumors exhibited
      secondary changes, such as fat necrosis, atrophy, and prominent hyalinization; 23
      tumors were histologically confirmed to be intramuscular. CONCLUSIONS: Lipomas of
      the oral and maxillofacial region occur most commonly in adult males in the
      parotid region, followed closely by the buccal mucosa. These tumors are uncommon
      in children. Interestingly, spindle cell lipomas are common in this region and
      comprise the majority of our parotid and lip tumors. Angiolipomas were absent in
      this anatomic region in this study. Secondary changes and atrophy should not be
      confused with the malignant histologic features of a liposarcoma.

PMID- 15472661
TI  - Calcifying odontogenic cyst with ameloblastic fibroma: report of three cases.
AB  - Although it is a rare event, odontogenic tumors such as ameloblastoma,
      ameloblastic fibroma (AF), ameloblastic fibro-odontoma, and odontoma have been
      reported associated with calcifying odontogenic cyst (COC). There are only four
      cases of COC with AF cited in the English literature. However, three of these
      four cases were either included in a review of a series of cases or reported as
      an abstract, and limited clinical and histological information was provided. We
      present three additional cases of COC with AF and discuss the management for this
      combined lesion. Because COC is known for its histologic diversity and variable
      clinical behavior, and the clinical significance of an association of COC with AF
      is still unknown, we think it is valuable to report COC with AF with detailed
      clinical and pathological documentation.

PMID- 15472662
TI  - 3D CT evaluation of masseter muscle morphology after setback osteotomy for
      mandibular prognathism.
AB  - OBJECTIVE: Following mandibular setback osteotomy, changes in the direction,
      length, and cross-sectional area of the masseter muscle were studied by means of
      computerized tomography (CT) images generated with a 3-dimensional (3D)
      reconstructive technique. STUDY DESIGN: Pre- and postoperative CT examinations
      were performed on 17 prognathic patients treated by sagittal split ramus
      osteotomy with rigid osteosynthesis and 13 patients treated by intraoral vertical
      ramus osteotomy without osteosynthesis. The pre- and postoperative masseter
      muscle direction and length were evaluated using 3D CT images observed from a
      lateral viewing angle. The cross-sectional area of the masseter muscle was first
      measured on an axial CT image of a selected slice level, following which the
      right-angle cross-sectional area of the muscle was revised using the measured
      area from the axial image. RESULTS: Postoperatively, anterior tilting of the
      masseter muscle was observed; however, masseter muscle length was unchanged.
      Three months postoperatively, a significant reduction in the cross-sectional area
      of the masseter muscle was seen. A tendency to revert back to the normal
      dimension was seen between 6 months and 1 year postoperatively. No significant
      difference was noted between the 2 surgical techniques. CONCLUSIONS: Three
      dimensional computed tomography is an adequate imaging modality for masseter
      muscle evaluation. The results of this study suggest the masseter muscle may
      undergo reversible atrophy after mandibular setback osteotomy.

PMID- 15472663
TI  - Development and evaluation of digital subtraction radiography computer program.
AB  - OBJECTIVE: We developed a new program for digital subtraction radiography (DSR)
      having useful functions to get the DSR image more accurately and efficiently. The
      purpose of this study was to evaluate the accuracy of the DSR image acquired
      using the new program as compared with the ready-made program. STUDY DESIGN: Four
      observers performed the DSR process using our program and the ready-made program
      for digital intraoral radiographs taken from incisor, premolar, and molar
      regions. The statistical difference was evaluated between the programs, between
      the observers, and between the regions. RESULTS: The DSR image using our program
      was superior to that with the ready-made program in all the observers and all the
      radiographed regions. Also, there was the statistical difference among the
      observers, especially in our program. CONCLUSION: The DSR image using the new
      program was very accurate compared with ready-made program, so the program was
      useful to get an accurate DSR image.

PMID- 15472664
TI  - The status of Spain's dental practices following the European Union directive
      concerning radiological installations.
AB  - OBJECTIVES: To assess the influence of new European Union (EU) legislation on
      dental radiology practices and the reduction in patient radiation exposure. STUDY
      DESIGN: A total of 7176 official reports from Spanish dental offices or clinics
      covering the period 1996 to 2001 were analyzed. RESULTS: Of the dental
      radiological installations inspected in 2001, 72.79% used the kilovoltage
      recommended by the EU (70 kVp) and 98.85% used at least 1.5 mm Al filtration. At
      least 90.11% of the installations had a focal film distance of 20 cm although
      there were no cases with a rectangular collimator as adapted to the size of film.
      Thirty percent of the installations showed a mechanical fault every year. In
      17.62% of cases the radiological film was stored in the exposure room. Few
      clinics (10.24%) used high-speed films and only 11.95% of clinics employed
      digital systems. The mean dose received by patients fell during the 5 years
      studied by 18.75%. Radiological equipment fulfilling the EU specifications
      emitted significantly lower doses than other nonapproved equipment. CONCLUSIONS:
      The introduction of legislation has resulted in a gradual improvement in dental
      radiology practices.

PMID- 15472665
TI  - Postoperative pain after endodontic retreatment: single- versus two-visit
      treatment.
AB  - OBJECTIVE: The purpose of this clinical study was to determine the effect of 1-
      or 2-visit root canal treatment on the postoperative pain in the retreatment
      cases. STUDY DESIGN: Two hundred eighteen cases that required retreatment were
      included in the study. Obturated and unfilled canal space and the status of
      periapical tissues were evaluated according to the PAI index. The patients were
      subcategorized in regard to the presence or the absence of preoperative pain.
      Approximately half of each category was treated in 1 appointment. After removing
      the previous root canal obturation materials and biomechanic preparation of root
      canals, the teeth in the 1-visit group were obturated at the first appointment by
      using AH 26 sealer and laterally compacted gutta-percha, and those in the 2-visit
      group were medicated with calcium hydroxide-chlorhexidine combination and then
      closed with a temporary filling material. One week after the initial appointment,
      patients were asked about the occurrence of postoperative pain. The level of
      discomfort was rated as no pain, mild pain, moderate pain, or severe pain (flare
      up). Data were statistically analyzed using the chi-squared and Fischer exact
      tests. RESULTS: Eight patients from the 1-visit group and 2 patients from the 2
      visit group had flare-ups. There was a statistical difference between the groups
      (P <.05). Two-visit root canal treatment was more effective in completely
      eliminating pain than 1-visit treatment of previously symptomatic teeth (P <.05).
      CONCLUSIONS: Two-visit endodontic treatment with intracanal medication was found
      to be effective in reducing postoperative pain of previously symptomatic teeth
      and decreased the number of flare-ups in all retreatment cases.

PMID- 15472666
TI  - Chlorhexidine substantivity in root canal dentin.
AB  - OBJECTIVE: The purpose of this investigation was to evaluate the substantivity of
      chlorhexidine (CHX) within a root canal system and to assess how long the CHX
      remains antimicrobially effective. STUDY DESIGN: Bovine roots were sectioned and
      standardized to 8 mm. Sections, which served as controls, were treated with 1%
      sodium hypochlorite and 1 mol/L EDTA, then obturated with gutta percha and AH26
      sealer. Experimental sections were treated similarly except they were placed in
      2% CHX for 10 minutes prior to obturation. Control specimens were divided into 4
      control groups and stored in saline for 1 day, 3 weeks, 6 weeks, and 12 weeks.
      Experimental specimens were divided into 4 groups and stored in saline for 1 day,
      3 weeks, 6 weeks, and 12 weeks. After their respective storage periods, all
      specimens were halved and canal wall dentin was ground out with Peeso reamers.
      Dentin specimens were agitated in 700 microl of saline for 5 hours to release
      CHX. After centrifugation the supernatants were analyzed with UV
      spectrophotometry at 253 nm. To determine whether the CHX from dentin samples
      remained antimicrobial, the extracts from experimental and control groups were
      mixed with cultures of Enterococcus faecalis. RESULTS: After 1 day of storage,
      the dentin extract contained approximately 0.0048% CHX. After 3, 6 and 12 weeks,
      dentin extracts contained approximately 0.0023%, 0.0016%, and 0.0010% CHX
      respectively. Extracts from the storage groups were found to be highly
      antimicrobial corresponding to the CHX concentration. CONCLUSION: The results of
      this study indicate that CHX is retained in root canal dentin in antimicrobially
      effective amounts for up to 12 weeks.

PMID- 15472667
TI  - Effect of modified Hedstrom files on instrumentation area produced by ProFile
      instruments in oval canals.
AB  - OBJECTIVE: To study the effect of a modified Hedstrom file called IqFile on the
      instrumentation shape of oval canals prepared with ProFile instruments. STUDY
      DESIGN: Fifty extracted premolars were divided into 3 groups of 16 teeth each.
      Group 1 was subjected to ProFile 0.04 rotary instrumentation to a size 6. Group 2
      followed the same technique, but also received buccolingual hand instrumentation
      with IqFiles to ISO size 70. Group 3 was instrumented similarly to group 2 but
      unmodified Hedstrom files were used. Teeth were sectioned at 1 and 3 mm from
      working length and photographed at 26x magnification. AutoCAD was used for
      measuring the percentage of instrumented area of the canal. RESULTS: ANOVA
      revealed that Group 2 was significantly better than Groups 1 (P=.00) and 3
      (P=.00) at the 1 mm level. At the 3 mm level Group 2 was significantly better
      than Group 1 (P=.03), but no differences were found between Groups 2 and 3
      (P=.15). CONCLUSION: The combination of ProFile and IqFile was found more
      effective in instrumenting oval canals at both the 1 and the 3 mm levels.
      However, at the 3 mm level no difference was detected between the use of IqFiles
      and the use of unmodified Hedstrom files.

PMID- 15472668
TI  - Effect of three different time periods of irrigation with EDTA-T, EDTA, and
      citric acid on smear layer removal.
AB  - OBJECTIVE: An in vitro study was conducted to evaluate the effect of EDTA-T, 17%
      EDTA, and 10% citric acid on the removal of smear layer from root canal dentin
      after final irrigation for 3, 10, and 15 min. STUDY DESIGN: Root canals of 90
      extracted human canines were divided into 9 groups of 10 teeth; each group
      received a final irrigation with one of the irrigants for the established time
      intervals. After irrigation, the teeth were split and prepared for SEM analysis
      to determine the number of open dentinal tubules. RESULTS: There were
      statistically significant better results (P <.05) when irrigation with 10% citric
      acid for 3 min was compared to 10 and 15 min, and when irrigation with EDTA for 3
      min was compared to 15 min. In all cases, irrigation for 3 min presented the
      greatest number of open dentinal tubules. There were no significant differences
      (P>.05) for the 3 time intervals of irrigation for EDTA-T, although there were a
      greater number of open tubules at 3 min. CONCLUSION: These 3 irrigants were
      effective at the shortest time tested and did not demonstrate an improved effect
      with an increase in time.

PMID- 15472669
TI  - ASGE guideline: The role of endoscopy in acute non-variceal upper-GI hemorrhage.

PMID- 15472670
TI  - Development and validation of a new, simplified endoscopic activity score for
      Crohn's disease: the SES-CD.
AB  - BACKGROUND: Healing of mucosal lesions appears to offer significant benefit and
      is an important end point in clinical trials of treatment for Crohn's disease.
      The only validated endoscopic activity score at present is the Crohn's Disease
      Endoscopic Index of Severity, which is complicated and time consuming and, hence,
      is unsuitable for routine use. The aim of this study was to develop and to
      prospectively validate a simpler endoscopic score of disease activity, the Simple
      Endoscopic Score for Crohn's Disease. METHODS: Selected endoscopic parameters
      (ulcer size, ulcerated and affected surfaces, stenosis) were scored from 0 to 3.
      Reproducibility for scoring of these parameters was evaluated through 71
      examinations in which the endoscopist was paired with an observer. The simplest
      score (Simple Endoscopic Score for Crohn's Disease) that was highly correlated
      with both the Crohn's Disease Endoscopic Index of Severity and Crohn's Disease
      Activity Index was derived for 70 patients and then was prospectively validated
      in 121 different patients with Crohn's disease. RESULTS: The interobserver
      agreement for all selected endoscopic variables was excellent (kappa coefficient
      0.791-1.000). Based on multiple linear regression, the Simple Endoscopic Score
      for Crohn's Disease resulted in the sum of the scores for ulcer size, ulcerated
      surface, affected surface, and luminal narrowing. In the validation phase of the
      study, a strong correlation was demonstrated for the Simple Endoscopic Score for
      Crohn's Disease with Crohn's Disease Endoscopic Index of Severity (r = 0.920). In
      addition, the Simple Endoscopic Score for Crohn's Disease was correlated to
      clinical parameters and serum C-reactive protein level. CONCLUSIONS: Simple
      Endoscopic Score for Crohn's Disease is a simple, reproducible, and easy-to-use
      endoscopic scoring system for Crohn's disease.

PMID- 15472671
TI  - Temporary placement of an expandable polyester silicone-covered stent for
      treatment of refractory benign esophageal strictures.
AB  - BACKGROUND: Benign, refractory esophageal strictures are an important therapeutic
      challenge. Metal stents occasionally have been used, but results have been
      disappointing. The present study assessed the safety and the efficacy of
      temporary placement of the new expandable polyester silicone-covered stent for
      management of problematic esophageal strictures. METHODS: Fifteen patients with
      benign esophageal strictures were treated by temporary (6 weeks) placement of an
      expandable polyester silicone-covered stent. All patients had previously been
      treated, unsuccessfully, by repetitive endoscopic dilation. RESULTS: Stent
      placement was successful in all patients. There was no procedure-related
      complication. Dilation with over-the-guidewire polyvinyl dilators was required
      before stent placement. With the stent in situ, dysphagia completely resolved in
      all patients. Six weeks after placement, one stent was found to have migrated
      into the stomach. In the remaining patients, the stent was easily removed with a
      foreign body forceps. The pretreatment dysphagia score was 3 (range 2-4); the
      post-treatment score was 1 (range 0-1) (p < 0.0005). Long-term resolution (mean
      follow-up 22.7 [2.6] months) of the stricture was achieved in 12 patients (80%).
      The treatment failed in 3 patients, all of whom continue to require periodic
      dilation. CONCLUSIONS: In patients with benign esophageal strictures refractory
      to conventional dilation, temporary placement of a removable expandable polyester
      silicone-covered stent may lead to long-term relief of dysphagia with minimal
      morbidity.

PMID- 15472672
TI  - Interobserver and intra-observer consistency in the endoscopic assessment of
      colonic pit patterns.
AB  - BACKGROUND: The colonic pit pattern is recognized as an aid to the differential
      diagnosis between hyperplastic lesions, adenoma, and carcinoma, and is a focus
      for observation by magnification chromoendoscopy, especially in Japan. This study
      evaluated intra- and interobserver agreement of experienced endoscopists in the
      assessment of colonic pit patterns when using the Kudo classification. METHODS: A
      total of 220 magnification chromoendoscopic pictures of colonic lesions were
      selected, of which 215 were collected from a consecutive series of patients. The
      pictures were randomly displayed twice to 6 experienced endoscopists at an
      interval of 1 week. Each picture was assessed for predominant pit pattern by
      using the classification of Kudo. Histopathologic diagnosis also was predicted
      based on the pit pattern diagnosis. Kappa statistics were used to estimate intra-
      and interobserver variation. RESULTS: The mean (standard deviation) inter- and
      intra-observer kappa values for experienced endoscopists were 0.716 (0.031) and
      0.810 (0.084), respectively. For prediction of histopathology according to the
      pit pattern diagnosis, the mean (standard deviation) inter- and intra-observer
      kappa values were 0.776 (0.032) (p = 0.001) and 0.862 (0.069) (p = 0.028),
      respectively. CONCLUSIONS: For experienced endoscopists, the inter- and intra
      observer reproducibility of the classification of colonic pit pattern is good.

PMID- 15472673
TI  - Safety, efficacy, and patient tolerance of a three-dose regimen of orally
      administered aqueous sodium phosphate for colonic cleansing before colonoscopy.
AB  - BACKGROUND: Sodium phosphate, administered orally, is an effective, well
      tolerated colonic cleansing agent. However, colonoscopic visualization is
      suboptimal in many patients after a conventional 2-dose regimen. This study
      assessed the safety, the efficacy, and patient tolerance of a 3-dose regimen of
      sodium phosphate. METHODS: Patients without cardiac, renal, or hepatic
      insufficiency were randomized to precolonoscopy purgation with 3 (45 mL) doses
      vs. two doses of aqueous sodium phosphate administered orally. Hemodynamic
      measurements and serum and urine biochemical tests were obtained at baseline and
      after purgation. Tolerance of the bowel preparation and colonoscopic
      visualization were assessed via questionnaires. RESULTS: Quality of colonic
      cleansing was significantly better with the 3-dose regimen compared with the 2
      dose regimen (p < 0.0001). No clinically significant adverse event was detected
      in either group. Subclinical orthostasis was observed in 5% of patients given the
      2-dose regimen vs. 3% of those who took the 3-dose regimen. Post-purgation
      hyperphosphatemia was greater in the 3-dose group vs. the 2-dose group (p =
      0.0003). No other significant differences in biochemistry were noted between the
      groups. Patient tolerance of the 2-dose regimen was better than the 3-dose
      regimen (p = 0.0379). CONCLUSIONS: A 3-dose regimen of orally administered sodium
      phosphate provides superior colonic cleansing without compromising volume status
      or serum biochemistry but is associated with poorer overall patient tolerance
      compared with a conventional 2-dose regimen.

PMID- 15472674
TI  - Bowel preparation increases the diagnostic yield of capsule endoscopy: a
      prospective, randomized, controlled study.
AB  - BACKGROUND: The aim of this study was to determine the value of small-bowel
      preparation for patients undergoing capsule endoscopy. METHODS: The study design
      was prospective, randomized, and controlled. Eighty patients referred for capsule
      endoscopy were randomized into two equal groups. Patients in Group A (mean age
      54.40 [15.65] years) ingested 2 L of a polyethylene glycol/electrolyte solution
      16 hours before the test, whereas patients in Group B (mean age 59.85 [14.58]
      years) prepared for the procedure by taking only clear liquids during the prior
      day. The primary outcome evaluated was the effect of bowel preparation on the
      quality of capsule images, as assessed with an objective scoring system in which
      cleansing was graded as "adequate" or "inadequate" by blinded examiners. A
      secondary outcome was the effect of bowel preparation on diagnostic yield. For
      this purpose, the results of capsule endoscopy were classified as positive
      findings, findings of uncertain significance, and no findings. RESULTS: Cleansing
      of the small intestine was considered "adequate" in 36 patients in Group A (90%)
      vs. 24 patients of Group B (60%) (p = 0.004). A diagnosis was established in 26
      patients in Group A (65%) compared with 12 patients in Group B (30%) (p = 0.003).
      CONCLUSIONS: Bowel preparation before capsule endoscopy improves visualization of
      the small intestine, which may lead to an improvement in diagnostic yield.

PMID- 15472675
TI  - Hyaluronic acid stimulates tumor-cell proliferation at wound sites.
AB  - BACKGROUND: For EMR, the submucosal injection of sodium hyaluronate has become
      popular, because this substance creates a more prominent and longer-lasting
      mucosal protrusion than normal saline solution. However, the effects of sodium
      hyaluronate on tumor growth at wound sites remain unclear. METHODS: For these
      experiments, a murine model with artificial wounds was used. Forty mice were
      randomly divided into two groups according to the substance to be injected into a
      wound: a sodium hyaluronate group and a control group. Tumors were created by
      inoculation of transplantable adenocarcinoma cell line colon 26. Two weeks later,
      the size, weight, proliferating cell nuclear antigen-labeling index, and CD44
      expression of the subcutaneous tumors were compared between the two groups of
      mice. RESULTS: There were significantly greater increases in the growth and the
      weight of subcutaneous tumors in the sodium hyaluronate group compared with the
      control group. The PCNA-labeling index of cancer cells also was higher in the
      sodium hyaluronate group. Immunohistochemistry and Western blot analysis
      demonstrated that the CD44 protein expression of cancer cells was higher in the
      sodium hyaluronate group vs. the control group. CONCLUSIONS: In this study,
      sodium hyaluronate enhanced both tumor growth and CD44 expression of cancer cells
      at wound sites, suggesting that the use of sodium hyaluronate for EMR might
      stimulate the growth of residual tumor cells.

PMID- 15472676
TI  - Does prophylactic pancreatic stent placement reduce the risk of post-ERCP acute
      pancreatitis? A meta-analysis of controlled trials.
AB  - BACKGROUND: Impaired drainage of the pancreatic duct is one of the possible
      triggers for post-ERCP acute pancreatitis. The aim of this meta-analysis was to
      determine whether temporary stent placement across the main pancreatic-duct
      orifice lowers the frequency of post-ERCP acute pancreatitis in patients at high
      risk for this complication. METHODS: Two reviewers systematically identified
      prospective studies that (1) compared the risk of post-ERCP acute pancreatitis in
      patients with pancreatic stent placement vs. no stent placement and (2) included
      patients at high risk of developing this complication. Studies were assessed for
      methodologic quality and variations in execution and design. Frequency and
      severity of post-ERCP acute pancreatitis were the primary outcomes evaluated.
      RESULTS: Five trials involving 481 patients were selected. Of the 481, 55 (11.4%)
      patients developed pancreatitis after ERCP. Patients in the no stent group had 3
      fold higher odds of developing pancreatitis compared with the stent group (15.5%
      vs. 5.8%; OR 3.2: 95% CI[1.6, 6.4]). Number needed to treat analysis showed that
      one in every 10 patients (95% CI[6,18]) could be expected to benefit from
      pancreatic-duct stent placement. CONCLUSIONS: Prophylactic temporary stent
      placement across the main pancreatic-duct orifice reduces the risk of post-ERCP
      acute pancreatitis in patients at risk for developing this complication.

PMID- 15472677
TI  - Endoscopic sphincterotomy by using pure-cut electrosurgical current and the risk
      of post-ERCP pancreatitis: a prospective randomized trial.
AB  - BACKGROUND: It has been suggested that the use of pure-cut electrosurgical
      current for endoscopic sphincterotomy may reduce the risk of post-ERCP
      pancreatitis. The aim of this study was to determine whether pure-cut current
      reduces the risk of pancreatitis compared with blend current. METHODS: Patients
      were randomly assigned to undergo sphincterotomy over a non-conductive guidewire
      with 30 W/sec pure-cut current or 30 W/sec blend-2 current by a blinded
      endoscopist. Serum amylase and lipase levels were determined 1 day before and
      within 24 hours after ERCP. Post-ERCP pancreatitis was the primary outcome of
      interest. Secondary outcomes were as follows: severity of immediate bleeding, as
      graded by a 3-point scale from 1 (no bleeding) to 3 (injection or balloon
      tamponade therapy required to stop bleeding) and evidence of delayed bleeding 24
      hours after ERCP. Analyses were performed in intention-to-treat fashion. RESULTS:
      A total of 246 patients were randomized (116 pure-cut current, 130 blend
      current). There were no differences in baseline characteristics between the
      groups. The overall frequency of post-ERCP pancreatitis was 6.9%, with no
      significant difference in frequency between treatment arms (pure cut, 7.8% vs.
      blend, 6.1%; p = 0.62). The difference in rates of pancreatitis between the two
      groups was 1.7%: 95% CI[-4.8%, 8.2%]. Six patients (2.4%) had delayed bleeding
      after ERCP, of which two required transfusion. There was a significant increase
      in minor bleeding episodes (grade 2) in the pure-cut group (p < 0.0001). Delayed
      episodes of bleeding were equal (n = 3) in each arm. CONCLUSIONS: The type of
      current used when performing endoscopic sphincterotomy does not appear to alter
      the risk of post-ERCP pancreatitis. The selection of electrosurgical current for
      biliary endoscopic sphincterotomy should be based on endoscopist preference.

PMID- 15472678
TI  - Endoscopic transpancreatic papillary septotomy for inaccessible obstructed bile
      ducts: Comparison with standard pre-cut papillotomy.
AB  - BACKGROUND: Access to the pancreatic or the bile duct is paramount to the success
      of diagnostic and therapeutic ERCP. Selective cannulation may be difficult
      because of the small size of the papilla and anatomic factors such as
      peripapillary diverticulum and gastrectomy with Billroth-II anastomosis.
      Currently, one of the techniques for gaining access in such cases is the pre-cut
      technique with a catheter that has a thin wire at the tip (needle knife). A less
      well-described pre-cut technique involves initial cannulation of the pancreatic
      duct with a "traction-type" papillotome and then incision through the "septum"
      toward the bile duct. The aim of this randomized trial was to compare the success
      and the complication rates of needle-knife sphincterotomy and transpancreatic
      sphincterotomy in achieving cannulation of an otherwise inaccessible bile duct.
      METHODS: Sixty-three consecutive patients with inaccessible bile ducts underwent
      pre-cut sphincterotomy either by needle-knife sphincterotomy (n = 34) or
      transpancreatic septotomy (n = 29). In patients with an accessible pancreatic
      duct who undergo needle-knife sphincterotomy, a short (2-3 cm) stent (5F-7F) was
      placed in the pancreatic duct to act as a guide and to reduce the risk of post
      procedure pancreatitis. All patients were hospitalized overnight for observation
      after pre-cut sphincterotomy. The outcomes measured were success rate and
      complications. Indications for pre-cut sphincterotomy were the following:
      suspected choledocholithiasis, 11 patients (17.5%); obstructive jaundice with
      negative CT findings, 19 patients (29.2%), or with positive CT findings, 13
      patients (20.6%); abdominal pain with elevated biochemical tests of liver
      function, 15 patients (23.8%); and miscellaneous, 5 patients (7.9%). RESULTS: In
      55 of 63 (87%) patients, the bile duct was selectively cannulated after pre-cut
      sphincterotomy. On a pre-protocol basis, the bile duct was cannulated in 29 of 29
      (100%) patients randomized to transpancreatic septotomy sphincterotomy and 26 of
      34 (77%) patients who underwent needle-knife sphincterotomy (p = 0.01). There
      were 7 complications, including bleeding (n = 2) and acute pancreatitis (n = 5).
      Complications were less frequent in the transpancreatic septotomy sphincterotomy
      group (1/29; 3.5%) compared with the needle-knife sphincterotomy group (6/34;
      17.7%). CONCLUSIONS: Transpancreatic pre-cut sphincterotomy can be performed with
      a high degree of success in patients with inaccessible obstructed bile ducts.
      Compared with standard needle-knife sphincterotomy, transpancreatic septotomy
      sphincterotomy has a significantly higher rate of bile duct cannulation and a
      lower complication rate.

PMID- 15472679
TI  - Endoscopic treatment of retained bile-duct stones by using a balloon catheter for
      electrohydraulic lithotripsy without cholangioscopy.
AB  - BACKGROUND: Electrohydraulic lithotripsy is a highly effective method for
      fragmenting biliary stones, but direct visual control is required. The efficacy
      and the safety of electrohydraulic lithotripsy without cholangioscopy by using a
      balloon catheter were evaluated in patients with bile-duct stones that could not
      be extracted by using standard techniques. METHODS: Nineteen patients with
      extrahepatic bile-duct stones that could not be extracted by using conventional
      endoscopic methods, e.g., mechanical lithotripsy, were selected to undergo
      electrohydraulic lithotripsy without peroral cholangioscopy. An electrohydraulic
      lithotripsy probe with a 3.0 F radio-opaque tip was inserted through a balloon
      catheter. Electrohydraulic lithotripsy was performed under fluoroscopy until the
      fragmented stone could be captured in a large basket for mechanical lithotripsy.
      Endoscopic removal of the fragments was attempted during the electrohydraulic
      lithotripsy session. RESULTS: Stones were successfully fragmented in 17 of 19
      patients. In 16 patients (84.2%), the bile duct was cleared of all stones. A mean
      of 1.8 endoscopic sessions was required for complete removal. Additional
      mechanical lithotripsy was performed in 9 (56.2%) of the 16 patients. Minor
      complications were noted in 4 patients (2 hemobilia, 1 pancreatitis, 1
      cholangitis). There was no 30-day mortality. CONCLUSIONS: For a selected group of
      patients with bile-duct stones not extractable by using standard techniques,
      fluoroscopically controlled electrohydraulic lithotripsy with a balloon catheter
      seems to be an effective method of fragmentation.

PMID- 15472680
TI  - Endoscopic therapy for bile leak based on a new classification: results in 207
      patients.
AB  - BACKGROUND: Bile leak is among the most common complications of cholecystectomy.
      Endoscopic therapy is empiric; a systematic approach to management of bile leak
      has not been established. METHODS: The severity of bile leak was classified by
      endoscopic retrograde cholangiography into low grade (leak identified only after
      intrahepatic opacification) or high grade (leak observed before intrahepatic
      opacification). Therapy was based on this distinction: biliary sphincterotomy
      alone for low-grade leaks and stent placement for high-grade leaks. The success
      of this strategy in consecutive patients treated between 1989 and 1999 was
      reviewed. RESULTS: A total of 207 patients (127 women, 80 men; median age 57
      years) with bile leak were referred for endoscopic management; 134 had undergone
      laparoscopic, and 72 had open cholecystectomy. Patients presented at a median of
      9 days (range 1-50 days) after surgery. Symptoms included pain (56%), jaundice
      (16%), fever (11%), and abdominal distension (7%). Persistent percutaneous
      drainage was present in 48%. Endoscopic retrograde cholangiography identified the
      leak site in 204 patients: cystic duct stump, 159 patients (78%); duct of
      Luschka, 26 (13%); other, 19 (9%). Of 104 patients with low-grade leaks, 75 had
      sphincterotomy alone; improvement occurred in 68 patients (91%). Subsequent
      treatment was required in 7 patients (6 stent, 1 surgery). Stents were placed in
      the remaining 29/104 patients for the following reasons: biliary stricture
      (11/29); coagulopathy, precluding sphincterotomy (8/29); severe sepsis (3/29);
      inadequate drainage after prior sphincterotomy (2/29); and unclear reasons
      (5/29). Of 100 patients with high-grade leaks, 97 had stent placement. Persistent
      leakage necessitated another stent insertion in 4 patients. Closure of the leak
      was documented by endoscopic retrograde cholangiography in all 97 patients. Three
      patients with leaks not amenable to endoscopic treatment were referred for
      surgery. Bile-duct stones were identified in 41 patients (28, low-grade group;
      13, high-grade group) and were extracted in all cases. Overall, complications
      occurred in 3 patients (2 pancreatitis, 1 perforation) and were managed
      conservatively with no mortality. CONCLUSIONS: A simple, practical endoscopic
      classification system for bile leak after cholecystectomy is proposed. This
      classification has clinical relevance for selection of optimal endoscopic
      management.

PMID- 15472681
TI  - Knowledge of indications for EUS among gastroenterologists and non
      gastroenterologists.
AB  - BACKGROUND: The level of awareness among non-gastroenterologists of the
      indications for EUS is unknown. This study assessed knowledge of the indications
      and the utility of EUS among gastroenterologists and non-gastroenterologists in a
      large multispecialty academic practice. METHODS: A questionnaire was designed
      that tested knowledge of the indications for EUS with respect to 4 organ systems:
      esophagus, gastroduodenum, hepatopancreatobiliary system and colorectum. The
      questionnaire was distributed by electronic mail to gastroenterologists, general
      internists, non-gastroenterologist subspecialists, and surgeons in a large
      multispecialty practice. RESULTS: The survey was distributed to 659 attending
      physicians of whom 227 (34%) replied: gastroenterologists (53%), internists
      (30%), non-gastroenterologist specialists (33%), and surgeons (28%). Knowledge of
      appropriate indications was highest among gastroenterologists (84.3%) compared
      with internists (68.9%), non-gastroenterologist specialists (65.4%), and surgeons
      (65.3%) (p < 0.0001). Among all non-gastroenterologists, knowledge of indications
      for hepatopancreatobiliary (mean 66.3% correct responses) and colorectal
      applications (64.0%) was inferior to knowledge of esophageal (71.5%) and
      gastroduodenal (83.5%) applications. CONCLUSIONS: Internists, non
      gastroenterologist specialists, and surgeons in a large multispeciality practice
      have moderate knowledge of the indications and the utility of EUS. Knowledge was
      at the lowest level for hepatopancreatobiliary and colorectal applications of EUS
      for all 3 groups of non-gastroenterologists. Future studies should focus on the
      education of non-gastroenterologists regarding the role of EUS and assess the
      impact of such education on the appropriateness of EUS referral patterns.

PMID- 15472682
TI  - Digital video for the documentation of colonoscopy.
AB  - BACKGROUND: The aim of this study was to determine whether digital video is
      suitable for the documentation of colonoscopy. Standards are required for the
      visual documentation of endoscopic findings and to optimize image quality while
      limiting file size and bandwidth requirements. METHODS: Video recordings of
      colonoscopy procedures were encoded using a common video compression method at
      selected data rates and resolutions. Twelve reviewers were selected, each of whom
      was assigned 8 video review sessions, each consisting of 5 colonoscopy
      procedures. The reviewers rated the following: level of confidence that the cecum
      was demonstrated, subjective quality of the video compared with actual
      videocolonoscopy, and whether the video was of "diagnostic quality." RESULTS:
      Reviewers were confident that the cecum was demonstrated in all cases except at
      the lowest data rate. The 1.0 Mbps standard interchange format video provided an
      optimal balance between quality and file size. CONCLUSIONS: For the documentation
      of colonoscopy, 1.0 Mbps is acceptable and results in a file size of 7.5
      Mbytes/min, which is manageable for most modern hospital and telehealth networks.

PMID- 15472683
TI  - Pancreas divisum, an evidence-based review: part II, patient selection and
      treatment.

PMID- 15472684
TI  - Endoscopic scoring system for Crohn's disease: viva the evolution!

PMID- 15472685
TI  - The development and the implementation of new endoscopic technology: what are the
      challenges?

PMID- 15472686
TI  - Small bowel capillary hemangioma.

PMID- 15472687
TI  - Jejunal stromal tumor.

PMID- 15472688
TI  - Eosinophilic enteritis.

PMID- 15472689
TI  - Duodenal vasculitis.

PMID- 15472690
TI  - Tracheoesophageal fistula.

PMID- 15472691
TI  - Fundal Dieulafoy's lesion.

PMID- 15472692
TI  - Metastatic thyroid lymphoma.

PMID- 15472693
TI  - Strongyloidiasis.

PMID- 15472694
TI  - Catheter-probe-assisted endoluminal US.

PMID- 15472695
TI  - Widespread EMR: a new technique for removal of large areas of mucosa.
AB  - BACKGROUND: Widespread EMR is a novel technique for resection of large areas of
      mucosa as a single bloc. Large lesion size (>2 cm) is a recognized limitation of
      current EMR techniques. This study assessed the technical feasibility, efficacy,
      and safety of widespread EMR in a porcine model. METHODS: Widespread EMR was
      performed in 6 pigs. A submucosal fluid cushion was created in the distal
      esophagus by using a 0.83% solution of hydroxypropyl methylcellulose. A mucosal
      strip 5 cm in length and including at least 50% of the luminal circumference was
      marginated by using a prototype cutting device. The proximal end of the mucosa
      was stripped from the submucosa by using a grasping forceps. The distal end was
      snare resected. Resected tissue was assessed histologically. Endoscopy was
      repeated at weeks 1 and 6. At week 6, a second widespread EMR of the mucosa on
      the wall opposite the initial resection was attempted to create a full
      circumferential resection. RESULTS: Widespread EMR was completed in all animals.
      The esophagus was denuded of mucosa in 5-cm lengths that included 50% of the
      circumference of the lumen. No procedure-related complication was observed.
      Histologic assessment demonstrated that the resection specimen included mucosa
      and submucosa but not muscularis propria. Endoscopy at 1 week revealed mucosal
      regrowth in two animals and ulceration in 4. At week 6, regrowth of mucosa was
      noted in all animals. The second wide EMR proved to be technically difficult and
      was associated with perforation, peri-esophageal abscess, and stricture
      formation. CONCLUSIONS: Wide EMR appears to be technically feasible for removal
      of large areas of mucosa. Mucosal strips 5 cm long that included over 50% of the
      luminal circumference were resected safely. Resection was followed by complete
      regrowth of the mucosa. However, a second wide EMR to create a circumferential
      resection proved to be technically difficult and unsafe.

PMID- 15472696
TI  - Laparoscopic radiofrequency ablation of hepatocellular carcinoma in the caudate
      lobe by using a new laparoscopic US probe with a forward-viewing convex-array
      transducer.
AB  - BACKGROUND: The use of a new end-fire type laparoscopic US probe with a forward
      viewing convex-array transducer allows the caudate lobe of the liver to be
      accessed. This study evaluated the preliminary results of treatment of
      hepatocellular carcinoma in the caudate lobe by using this new instrument.
      METHODS: Three patients with hepatocellular carcinoma in the caudate lobe were
      selected. A laparoscopic US probe, with a forward-viewing convex-array transducer
      at the tip and a guide groove for puncture on the back, was used to monitor the
      position of the radiofrequency ablation needle during the treatment. RESULTS:
      Ablation was performed without complication in all cases. Complete necrosis of
      the tumor was confirmed by postoperative CT. At a mean follow-up of 30.3 months,
      no local recurrence was observed in any patient. CONCLUSIONS: Radiofrequency
      ablation of hepatocellular carcinoma in the caudate lobe of the liver by using a
      new laparoscopic US probe with a forward-viewing convex-array transducer at the
      tip was safe and effective.

PMID- 15472697
TI  - Frequency and significance of acute intracystic hemorrhage during EUS-FNA of
      cystic lesions of the pancreas.
AB  - BACKGROUND: Complications from EUS-guided FNA of cystic lesions of the pancreas
      are infrequent. Although several studies have evaluated infectious complications
      of EUS-guided FNA in this setting, the frequency and the clinical significance of
      intracystic hemorrhage have not been determined. This study assessed the
      frequency of acute intracystic hemorrhage during EUS-guided FNA of pancreatic
      cystic lesions. The characteristic EUS appearance is described. METHODS: EUS
      guided FNA of pancreatic cyst lesions was performed in 50 patients (July 2000 to
      June 2003). Patients were followed prospectively for the development of
      complications. OBSERVATIONS: Acute intracystic hemorrhage occurred during EUS
      guided FNA at the site of aspiration in 3 patients (6%: 95% confidence interval
      [1.3%, 16.6%]). Endosonographically, the bleeding manifested as a small
      hyperechoic area at the puncture site that progressed gradually over a few
      minutes to involve the majority of the cyst cavity. EUS-guided FNA was terminated
      when bleeding was observed. One patient was asymptomatic, but two patients
      experienced abdominal pain transiently. All patients were treated with a short
      course of orally administered antibiotics and were observed as outpatients.
      Clinical history and laboratory parameters did not predict which patients were at
      risk for intracystic hemorrhage. CONCLUSIONS: Acute intracystic hemorrhage is a
      rare complication of EUS-guided FNA; it has a characteristic EUS appearance.
      Recognition of this event is important, because it permits termination of the
      procedure and thereby minimizes the potential for more serious bleeding.

PMID- 15472699
TI  - Removal of self-expandable metallic Wallstents.
AB  - BACKGROUND: The self-expandable metallic stent is increasingly being used for
      management of malignant biliary strictures. In certain clinical situations, it
      also may be an alternative treatment for benign strictures. The ability to remove
      a metallic stent would be advantageous to the management of many biliary
      strictures, regardless of etiology. METHODS: Stent removal was considered in 18
      patients with either covered or uncovered Wallstents placed for biliary
      obstruction. Indications for placement were the following: unresectable cancer
      (10), chronic pancreatitis (3), benign biliary stricture (3), impacted stone (1),
      and papillary adenoma (1). OBSERVATIONS: Stent removal was successful in 17
      patients. Mean follow-up after removal was 9 months. Thirteen removed stents were
      covered. Indications for removal were the following: occlusion (5), migration
      (3), facilitation of hemostasis (2), malposition (3), persistent cholestasis (1),
      stone extraction (1), stricture revision (1), gallbladder fossa abscess (1), and
      abdominal pain (1). Devices and techniques used for successful removal included a
      snare, an extraction balloon, and electrocoagulation combined with forceps.
      CONCLUSIONS: Removal of uncovered Wallstents is difficult and typically requires
      a combination of techniques. Removal of covered Wallstents with a snare is
      relatively simple and safe, and can be followed immediately by corrective
      therapy. Insertion of a covered Wallstent should be considered as initial therapy
      when malignant biliary obstruction is suspected but unconfirmed.

PMID- 15472698
TI  - Endoscopic clip application for closure of esophageal perforations caused by EMR.
AB  - BACKGROUND: With increasing use of EMR for early stage esophageal carcinoma, the
      number of cases of iatrogenic esophageal perforation is likely to increase. This
      study evaluated the results of endoscopic clip application for treatment of
      perforations caused by EMR in patients with esophageal carcinoma. METHODS: Among
      185 patients who underwent EMR for esophageal carcinoma, esophageal perforation
      occurred in 3 patients (1.6%). Metallic clips were immediately applied
      endoscopically to close the perforations. OBSERVATIONS: All 3 patients were
      observed closely and were managed conservatively (intravenous hyperalimentation,
      antibiotics) after closure of the perforation. They were discharged without any
      further serious complication. CONCLUSIONS: When esophageal perforation caused by
      EMR is immediately recognized, endoscopic application of metallic clips is
      appropriate therapy. However, patients must be carefully monitored for the
      development of generalized mediastinitis.

PMID- 15472700
TI  - EUS-guided trucut biopsy with immunohistochemical analysis of a gastric stromal
      tumor.

PMID- 15472701
TI  - Lymphoid follicular proctitis mimicking rectal lymphoma: diagnosis by EMR.

PMID- 15472702
TI  - Removal of embedded foreign bodies in the GI tract after endoscopic division by
      using laser light.

PMID- 15472703
TI  - Fracture of a biliary expandable metallic stent.

PMID- 15472704
TI  - Cholangiocarcinoma arising from a choledochoduodenal anastomosis without causing
      jaundice.

PMID- 15472705
TI  - Double bile duct with ectopic drainage into stomach.

PMID- 15472706
TI  - Gastric bezoar treated endoscopically with a carbonated beverage: case report.

PMID- 15472707
TI  - Gastric gland heterotopic in muscularis mucosa treated by endoscopic polypectomy:
      a case report.

PMID- 15472708
TI  - Acute gastroparesis secondary to gastric emphysema: a rare complication of
      balloon dilation.

PMID- 15472709
TI  - Is metallic clip application reliable for perforations of the stomach caused by
      EMR?

PMID- 15472710
TI  - Clinical vigilance is as important as prophylactic antibiotics in patients with
      cirrhosis who undergo GI endoscopy.

PMID- 15472711
TI  - Restoration of the cystic fibrosis transmembrane conductance regulator function
      by splicing modulation.
AB  - A significant fraction of disease-causing mutations affects pre-mRNA splicing.
      These mutations can generate both aberrant and correct transcripts, the level of
      which varies among different patients. An inverse correlation was found between
      this level and disease severity, suggesting a role for splicing regulation as a
      genetic modifier. Overexpression of splicing factors increased the level of
      correctly spliced RNA, transcribed from minigenes carrying disease-causing
      splicing mutations. However, whether this increase could restore the protein
      function was unknown. Here, we demonstrate that overexpression of Htra2-beta1 and
      SC35 increases the level of normal cystic fibrosis transmembrane conductance
      regulator (CFTR) transcripts in cystic-fibrosis-derived epithelial cells carrying
      the 3849+10 kb C --> T splicing mutation. This led to activation of the CFTR
      channel and restoration of its function. Restoration was also obtained by sodium
      butyrate, a histone deacetylase inhibitor, known to upregulate the expression of
      splicing factors. These results highlight the therapeutic potential of splicing
      modulation for genetic diseases caused by splicing mutations.

PMID- 15472712
TI  - Iron-induced oligomerization of yeast frataxin homologue Yfh1 is dispensable in
      vivo.
AB  - The neurodegenerative disease Friedreich's ataxia is caused by reduced levels of
      frataxin, a mitochondrial matrix protein. The in vivo role of frataxin is under
      debate. Frataxin, as well as its yeast homologue Yfh1, binds multiple iron atoms
      as an oligomer and has been proposed to function as a crucial iron-storage
      protein. We identified a mutant Yfh1 defective in iron-induced oligomerization.
      This mutant protein was able to replace functionally wild-type Yfh1, even when
      expressed at low levels, when mitochondrial iron levels were high and in mutant
      strains having deletions of genes that had synthetic growth defects with a YFH1
      deletion. The ability of an oligomerization-deficient Yfh1 to function in vivo
      suggests that oligomerization, and thus oligomerization-induced iron storage, is
      not a critical function of Yfh1. Rather, the capacity of this oligomerization
      deficient mutant to interact with the Isu protein suggests a more direct role of
      Yfh1 in iron-sulphur cluster biogenesis.

PMID- 15472713
TI  - Bypassing tumor-associated immune suppression with recombinant adenovirus
      constructs expressing membrane bound or secreted GITR-L.
AB  - Recent evidence has resurrected the concept of specialized populations of T
      lymphocytes that are able to suppress an antigen-specific immune response. T
      regulatory cells (T-reg) have been characterized as CD4+ CD25+ T cells. Previous
      reports describing differential gene expression analysis have shown that the
      glucocorticoid-induced tumor necrosis family receptor family-related gene (GITR)
      is upregulated in these cells. Furthermore, antibodies specific for GITR have
      been shown to inhibit the T-suppressor function of CD4+ CD25+ T-reg. The ligands
      for both mouse and human GITR have been cloned recently. We have inserted the
      sequences for natural, membrane-bound GITR-ligand (GITR-L) and a truncated
      secreted form of GITR-L (GITR-Lsol) into the adenovirus-5 genome. Coculture
      experiments show that cells infected with Ad-GITR-L and supernatants from cells
      infected with Ad-GITR-Lsol can increase the proliferation of both CD4+ CD25- and
      CD8+ T cells in response to anti-CD3 stimulation, in the presence, as well as in
      the absence, of CD4+ CD25+ T cells. The virus constructs were injected into
      growing B16 melanoma tumors. Ad-GITR-L was shown to attract infiltration with
      both CD4+ and CD8+ T cells. Both constructs were shown to inhibit tumor growth.

PMID- 15472714
TI  - Replication-selective oncolytic viruses in the treatment of cancer.
AB  - In the search for novel strategies, oncolytic virotherapy has recently emerged as
      a viable approach to specifically kill tumor cells. Unlike conventional gene
      therapy, it uses replication competent viruses that are able to spread through
      tumor tissue by virtue of viral replication and concomitant cell lysis. Recent
      advances in molecular biology have allowed the design of several genetically
      modified viruses, such as adenovirus and herpes simplex virus that specifically
      replicate in, and kill tumor cells. On the other hand, viruses with intrinsic
      oncolytic capacity are also being evaluated for therapeutic purposes. In this
      review, an overview is given of the general mechanisms and genetic modifications
      by which these viruses achieve tumor cell-specific replication and antitumor
      efficacy. However, although generally the oncolytic efficacy of these approaches
      has been demonstrated in preclinical studies the therapeutic efficacy in clinical
      trails is still not optimal. Therefore, strategies are evaluated that could
      further enhance the oncolytic potential of conditionally replicating viruses. In
      this respect, the use of tumor-selective viruses in conjunction with other
      standard therapies seems most promising. However, still several hurdles regarding
      clinical limitations and safety issues should be overcome before this mode of
      therapy can become of clinical relevance.

PMID- 15472715
TI  - CXCR4 knockdown by small interfering RNA abrogates breast tumor growth in vivo.
AB  - Breast cancer cells express the chemokine receptor CXCR4 and frequently
      metastasize to organs with an abundant source of the CXCR4 ligand, stromal cell
      derived factor 1 (SDF-1). The chemokine receptor CXCR4 plays an active role in
      the metastasis of breast cancer. Here, we show that a small interfering RNA
      (siRNA) against CXCR4 effectively downregulates CXCR4 expression in human MDA-MB
      231 breast cancer cells, leading to significant decrease in breast cancer cell
      invasion and adhesion. It was further found that tumor cells lacking CXCR4
      expression proliferated at a much slower rate than control cells in vitro.
      Surprisingly, tumor cells lacking CXCR4 expression failed to grow in SCID mice in
      repeated experiments, providing the first direct evidence for an essential role
      of CXCR4 in breast cancer growth in vivo. This finding suggests an expanded role
      for the CXCR4 molecule in tumor cell growth in vivo, in addition to its role in
      breast cancer metastasis. This study implies the CXCR4 molecule as a potential
      target to control breast tumor growth as well as metastasis.

PMID- 15472716
TI  - Adjuvant interleukin-12 gene therapy for the management of colorectal liver
      metastases.
AB  - In humans, no efficient treatment exists not only against multifocal liver
      metastases (LM) but also against recurrent microscopic liver metastases within
      the liver remnant following curative liver resection. Furthermore, in
      nonmultifocal LM, partial liver resection could be performed, but in more than
      50% of the patients, tumor recurrence within liver remnant is observed, partly
      due to the growth of dormant cancer cells in the setting of postoperative host
      immune dysfunction. We investigated the therapeutic potential of interleukin-12
      (IL-12) immuno-gene therapies in these experimental models under total vascular
      exclusion (TVE) of the liver. In rats with multiple LM of DHDK12 colon cancer
      cells, we observed a significant reduction in tumor volume after retroviral
      mediated gene transfer of either herpes simplex virus thymidine kinase (HSV1-TK)
      and ganciclovir (GCV) administration, or IL-12. Combined treatment with HSV1
      TK/GCV and IL-12 resulted in improved tumor volume reduction and even survival.
      In rats with recurrent microscopic DHDK12 LM established after partial liver
      resection, we observed significantly decreased recurrent tumor volumes and
      increased survival after retroviral-mediated IL-12 gene transfer. In both
      settings, immunohistological analysis revealed that IL-12 immuno-gene therapy was
      accompanied by an infiltration of CD8+ T lymphocytes within the tumors.
      Altogether, our results suggest that IL-12 adjuvant gene therapy could improve
      the management of patients with either resectable or unresectable LM.

PMID- 15472717
TI  - Is Valsalva manoeuvre useful in diagnosing dural caroticocavernous fistulas?

PMID- 15472718
TI  - Disseminated paracoccidioidomycosis with chorioretinal involvement.

PMID- 15472719
TI  - Trypan blue vital staining of the anterior lens capsule in the management of
      cataract in true exfoliation of the lens capsule.

PMID- 15472720
TI  - Peptide substrate identification for yeast Hsp40 Ydj1 by screening the phage
      display library.
AB  - We have identified a peptide substrate for molecular chaperone Hsp40 Ydj1 by
      utilizing the combination of phage display library screening and isothemol
      titration calirimetry (ITC). The initial peptide substrate screening for Hsp40
      Ydj1 has been carried out by utilizing a 7-mer phage display library. The peptide
      sequences from the bio-panning were synthesized and object to the direct affinity
      measurement for Hsp40 Ydj1 by isothemol titration calirimetry studies. The
      peptide which has the measurable affinity with Ydj1 shows enriched hydrophobic
      residues in the middle of the substrate fragment. The peptide substrate
      specificity for molecular chaperone Hsp40 has been analyzed.

PMID- 15472722
TI  - Screening of Compounds Toxicity against Human Monocytic cell line-THP-1 by Flow
      Cytometry.
AB  - The worldwide rapid increase in bacterial resistance to numerous antibiotics
      requires on-going development of new drugs to enter the market. As the
      development of new antibiotics is lengthy and costly, early monitoring of
      compound's toxicity is essential in the development of novel agents. Our interest
      is in a rapid, simple, high throughput screening method to assess cytotoxicity
      induced by potential agents. Some intracellular pathogens, such as Mycobacterium
      tuberculosis primary site of infection is human alveolar macrophages. Thus,
      evaluation of candidate drugs for macrophage toxicity is crucial. Protocols for
      high throughput drug toxicity screening of macrophages using flow cytometry are
      lacking in the literature. For this application we modified a preexisting
      technique, propidium iodide (PI) exclusion staining and utilized it for rapid
      toxicity tests. Samples were prepared in 96 well plates and analyzed by flow
      cytometry, which allowed for rapid, inexpensive and precise assessment of
      compound's toxicity associated with cell death.

PMID- 15472721
TI  - Using the cre-lox recombination system to assess functional impairment caused by
      amino acid substitutions in yeast proteins.
AB  - A method was developed to assess the functional significance of a sequence motif
      in yeast Upf3p, a protein required for nonsense-mediated mRNA decay (NMD). The
      motif lies at the edge of the Upf3p-Upf2p interaction domain, but at the same
      time resembles the canonical leucine-rich nuclear export sequence (NES) found in
      proteins that bind Crm1p exportin. To test the function of the putative NES, site
      directed mutations that cause substitutions of conserved NES-A residues were
      first selected to identify hypermorphic alleles. Next, a portable Crm1p-binding
      NES from HIV-1 Rev protein that functions in yeast was fused en masse to the C
      terminus of variant Upf3 proteins using loxP sites recognized by bacterial cre
      recombinase. Finally, variant Upf3-Rev proteins that were functional in NMD were
      selected and examined for the types of amino acid substitutions present in NES-A.
      The mutational analysis revealed that amino acid substitutions in the Upf3 NES
      impair both nuclear export and the Upf2p-Upf3p interaction, both of which are
      required for Upf3p to function in NMD. The method described in this report could
      be modified for the genetic analysis of a variety of portable protein domains.

PMID- 15472723
TI  - Precise temperature control in microfluidic devices using Joule heating of ionic
      liquids.
AB  - Microfluidic devices for spatially localised heating of microchannel environments
      were designed, fabricated and tested. The devices are simple to implement, do not
      require complex manufacturing steps and enable intra-channel temperature control
      to within +/-0.2 degrees C. Ionic liquids held in co-running channels are Joule
      heated with an a.c. current. The nature of the devices means that the internal
      temperature can be directly assessed in a facile manner.

PMID- 15472724
TI  - "Microcanals" for micropipette access to single cells in microfluidic
      environments.
AB  - We demonstrate the fabrication and operation of "microcanals"(i.e. open-air
      microfluidic channels without a roof), which enable micropipette manipulation and
      probing of cells within a microfluidic environment. The microcanal devices are
      fabricated in PDMS on glass substrates using a PDMS membrane transferring
      technique. Here we show patch-clamp electrophysiological recording and
      intracellular dye injection performed on cells seeded in microcanals.

PMID- 15472725
TI  - Molded polyethylene glycol microstructures for capturing cells within
      microfluidic channels.
AB  - The ability to control the deposition and location of adherent and non-adherent
      cells within microfluidic devices is beneficial for the development of micro
      scale bioanalytical tools and high-throughput screening systems. Here, we
      introduce a simple technique to fabricate poly(ethylene glycol)(PEG)
      microstructures within microfluidic channels that can be used to dock cells
      within pre-defined locations. Microstructures of various shapes were used to
      capture and shear-protect cells despite medium flow in the channel. Using this
      approach, PEG microwells were fabricated either with exposed or non-exposed
      substrates. Proteins and cells adhered within microwells with exposed substrates,
      while non-exposed substrates prevented protein and cell adhesion (although the
      cells were captured inside the features). Furthermore, immobilized cells remained
      viable and were stained for cell surface receptors by sequential flow of
      antibodies and secondary fluorescent probes. With its unique strengths in utility
      and control, this approach is potentially beneficial for the development of cell
      based analytical devices and microreactors that enable the capture and real-time
      analysis of cells within microchannels, irrespective of cell anchorage
      properties.

PMID- 15472726
TI  - A double plasma gas chromatography injector and detector.
AB  - A direct-current, chip-based plasma has been used for gas sample injection in gas
      chromatography. A second identical plasma chip has been used as the excitation
      source for an optical emission detector. The first plasma is normally continually
      sustained during operation, causing continuous ionisation/fragmentation of the
      sample, whilst the second plasma records the optical emission downstream. For
      injection, the first plasma is briefly interrupted, introducing a "plug" of
      unmodified sample into the system. Injection plug sizes of between 5 and 50
      [micro sign]l have been reproducibly obtained, although significantly smaller
      volumes may be possible with the use of smaller cross-section columns, lower flow
      rates and/or shorter plasma interruption times.

PMID- 15472727
TI  - Suppression of non-specific adsorption using sheath flow.
AB  - The use of a confining sheath fluid within a microfluidic channel in order
      prevent non-specific adsorption of analytes to the walls of microchannels is
      demonstrated. A sheath-flow channel fabricated using laser cutting of Mylar films
      is developed. Numerical simulations of convective and diffusive mass transport
      within the channel are presented. The device is characterized experimentally
      using epifluorescence microscopy. It is demonstrated that the device is capable
      of preventing the adsorption of Rhodamine B to the walls of the channel for a
      period that would allow for adsorption-free T-sensor measurements to be made
      within the core of the flow channel. Generalized scaling rules based on the
      diffusion coefficient, sheath thickness and affinity of the potential adsorbant
      for the surface material are discussed. The controlled adsorption of the protein
      bovine serum albumin (BSA) to a gold surface is also demonstrated using SPR
      microscopy.

PMID- 15472728
TI  - Continuous cell washing and mixing driven by an ultrasound standing wave within a
      microfluidic channel.
AB  - Ultrasound standing wave radiation force and laminar flow have been used to
      transfer yeast cells from one liquid medium to another (washing) by a continuous
      field-flow fractionation (FFF) approach. Two co-flowing streams, a cell-free
      suspending phase (flow rate > 50% of the total flow-through volume) and a yeast
      suspension, were introduced parallel to the nodal plane of a 3 MHz standing wave
      resonator. The resonator was fabricated to have a single pressure nodal plane at
      the centre line of the chamber. Laminar flow ensured a stable interface was
      maintained as the two suspending phases flowed through the sound field.
      Initiation of the ultrasound transferred cells to the cell-free phase within 0.5
      s. This particle transfer procedure circumvents the pellet formation and re
      suspension steps of centrifuge based washing procedures. In addition, fluid
      mixing was demonstrated in the same chamber at higher sound pressures. The
      channel operates under negligible back-pressure (cross-section, 0.25 [times] 10
      mm) and with only one flow convergence and one flow division step, the channel
      cannot be easily blocked. The force acting on the cells is small; less than that
      experienced in a centrifuge generating 100g. The acoustically-driven cell
      transfer and mixing procedures described may be particularly appropriate for the
      increasingly complex operations required in molecular biology and microbiology
      and especially for their conversion to continuous flow processes.

PMID- 15472729
TI  - System-oriented dispersion models of general-shaped electrophoresis
      microchannels.
AB  - This paper presents a system-oriented model for analyzing the dispersion of
      electrophoretic transport of charged analyte molecules in a general-shaped
      microchannel, which is represented as a system of serially connected elemental
      channels of simple geometry. Parameterized analytical models that hold for
      analyte bands of virtually arbitrary initial shape are derived to describe
      analyte dispersion, including both the skew and broadening of the band, in
      elemental channels. These models are then integrated to describe dispersion in
      the general-shaped channel using appropriate parameters to represent interfaces
      of adjacent elements. This lumped-parameter system model offers orders-of
      magnitude improvement in computational efficiency over full numerical
      simulations, and is verified by results from experiments and numerical
      simulations. The model is used to perform a systematic parametric study of
      serpentine channels consisting of a pair of complementary turn microchannels, and
      the results indicate that dispersion in a particular turn can contribute to
      either an increase or decrease of the overall band broadening. The efficiency and
      accuracy of the system model is further demonstrated by its application to
      general-shaped channels that occur in practice, including a serpentine channel
      with multiple complementary turns and a multi-turn spiral-shaped channel. The
      results indicate that our model is an accurate and efficient simulation tool
      useful for designing optimal electrophoretic separation microchips.

PMID- 15472730
TI  - Cell transport via electromigration in polymer-based microfluidic devices.
AB  - Electrokinetic transport of Escherichia coli and Saccharomyces cerevisiae
      (baker's yeast) cells was evaluated in microfluidic devices fabricated in
      pristine and UV-modified poly(methyl methacrylate)(PMMA) and polycarbonate (PC).
      Chip-to-chip reproducibility of the cell's apparent mobilities (micro(app))
      varied slightly with a RSD of approximately 10%. The highest micro(app) for
      baker's yeast cells was observed in UV-modified PC with 0.5 mM PBS (pH = 7.4),
      and the lowest was measured in pristine PMMA with 20 mM PBS (pH = 7.4). Baker's
      yeast in all devices migrated toward the cathode because of their smaller
      electrophoretic mobility compared to the EOF. In 0.5 mM and 1 mM PBS, E. coli
      cells migrated toward the anode in all cases, opposite to the direction of the
      EOF due to their larger electrophoretic mobility. E. coli cells in 20 mM PBS
      migrated toward the cathode, which indicated that the electrophoretic mobility of
      E. coli cells decreased at higher ionic strengths. Observed differential
      migrations of E. coli and baker's yeast cells in appropriately prepared polymer
      microchips were used as the basis for selective introduction into microfluidic
      devices of only one type of cell. As a working model, experiments were performed
      with E. coli and RBCs (red blood cells). RBCs migrated toward the cathode in
      pristine PMMA with 1 mM and 20 mM PBS (pH = 7.4), opposite to the direction of
      the E. coli cells. By judicious choice of the buffer concentration in which the
      cell suspension was prepared and the polymer material, RBCs or E. coli cells were
      selectively introduced into the microdevice, which was monitored via laser
      backscatter signals.

PMID- 15472731
TI  - Capacitive sensing of droplets for microfluidic devices based on thermocapillary
      actuation.
AB  - The design and performance of a miniaturized coplanar capacitive sensor is
      presented whose electrode arrays can also function as resistive microheaters for
      thermocapillary actuation of liquid films and droplets. Optimal compromise
      between large capacitive signal and high spatial resolution is obtained for
      electrode widths comparable to the liquid film thickness measured, in agreement
      with supporting numerical simulations which include mutual capacitance effects.
      An interdigitated, variable width design, allowing for wider central electrodes,
      increases the capacitive signal for liquid structures with non-uniform height
      profiles. The capacitive resolution and time response of the current design is
      approximately 0.03 pF and 10 ms, respectively, which makes possible a number of
      sensing functions for nanoliter droplets. These include detection of droplet
      position, size, composition or percentage water uptake for hygroscopic liquids.
      Its rapid response time allows measurements of the rate of mass loss in
      evaporating droplets.

PMID- 15472732
TI  - Microfluidic biosensing systems. Part I. Development and optimisation of
      enzymatic chemiluminescent micro-biosensors based on silicon microchips.
AB  - Chemiluminescent (CL) enzyme-based flow-through microchip biosensors (micro
      biosensors) for detection of glucose and ethanol were developed for the purpose
      of monitoring real-time production and release of glucose and ethanol from
      microchip immobilised yeast cells. Part I of this study focuses on the
      development and optimisation of the micro-biosensors in a microfluidic sequential
      injection analysis (microSIA) system. Glucose oxidase (GOX) or alcohol oxidase
      (AOX) was co-immobilised with horseradish peroxidase (HRP) on porous silicon flow
      through microchips. The hydrogen peroxide produced from oxidation of the
      corresponding analyte (glucose or ethanol) took part in the chemiluminescent (CL)
      oxidation of luminol catalysed by HRP enhanced by addition of p-iodophenol (PIP).
      All steps in the microSIA system, including control of syringe pump,
      multiposition valve (MPV) and data readout, were computer controlled. The
      influence of flow rate and luminol- and PIP concentration were investigated using
      a 2(3)-factor experiment using the GOX-HRP sensor. It was found that all
      estimated single factors and the highest order of interaction were significant.
      The optimum was found at 250 microM luminol and 150 microM PIP at a flow rate of
      18 microl min(-1), the latter as a compromise between signal intensity and
      analysis time. Using the optimised system settings one sample was processed
      within 5 min. Two different immobilisation chemistries were investigated for both
      micro-biosensors based on 3-aminopropyltriethoxsilane (APTS)- or polyethylenimine
      (PEI) functionalisation followed by glutaraldehyde (GA) activation. GOX-HRP micro
      biosensors responded linear in a log-log format within the range 10-1000 microM
      glucose. Both had an operational stability of at least 8 days, but the PEI-GOX
      HRP sensor was more sensitive. The AOX-HRP micro-biosensors responded linear (log
      log) in the range between 1 and 10 mM ethanol, but the PEI-AOX-HRP sensor was in
      general more sensitive. Both sensors had an operational stability of at least 8
      h, but with a half-life of 2-3 days.

PMID- 15472733
TI  - Microfluidic biosensing systems. Part II. Monitoring the dynamic production of
      glucose and ethanol from microchip-immobilised yeast cells using enzymatic
      chemiluminescent micro-biosensors.
AB  - A microfluidic flow injection (microFIA) system was employed for handling and
      monitoring of cell-released products from living cells immobilised on silicon
      microchips. The dynamic release of glucose and ethanol produced from sucrose by
      immobilised Saccharomyces cerevisiae cells was determined using microchip
      biosensors (micro-biosensors) with either co-immobilised glucose oxidase
      horseradish peroxidase (GOX-HRP), or alcohol oxidase-horseradish peroxidase (AOX
      HRP), catalysing a series of reactions ending up with chemiluminescence (CL)
      generated from HRP-catalysed oxidation of luminol in presence of p-iodophenol
      (PIP). The yeast cells were attached by first treating them with polyethylenimine
      (PEI) followed by adsorption to the microchip surface. The cell loss during
      assaying was evaluated qualitatively using scanning electron microscopy (SEM),
      showing that no cells were lost after 35 min liquid handling of the cell chip at
      10 microl min(-1). The enzymes were immobilised on microchips via PEI-treatment
      followed by glutaraldehyde (GA) activation. The GOX-HRP micro-biosensors could be
      used during five days without any noticeable decrease in response, while the AOX
      HRP micro-biosensors showed continuously decreasing activity, but could still be
      used employing calibration correction. The glucose and ethanol released from the
      immobilised yeast chips were quantitatively monitored, by varying the incubation
      time with sucrose, showing the possibilities and advantages of using a
      microfluidic system set-up for cell-based assays.

PMID- 15472734
TI  - Surface micromachined electrostatically actuated micro peristaltic pump.
AB  - An electrostatically actuated micro peristaltic pump is reported. The micro pump
      is entirely surface micromachined using a multilayer parylene technology. Taking
      advantage of the multilayer technology, the micro pump design enables the pumped
      fluid to be isolated from the electric field. Electrostatic actuation of the
      parylene membrane using both DC and AC voltages was demonstrated and applied to
      fluid pumping based on a 3-phase peristaltic sequence. A maximum flow rate of 1.7
      nL min(-1) and an estimated pumping pressure of 1.6 kPa were achieved at 20 Hz
      phase frequency. A dynamic analysis was also performed with a lumped-parameter
      model for the peristaltic pump. The analysis results allow a quantitative
      understanding of the peristaltic pumping operation, and correctly predict the
      trends exhibited by the experimental data. The small footprint of the micro pump
      is well suited for large-scale integration of microfluidics. Moreover, because
      the same platform technology has also been used to fabricate other devices (e.g.
      valves, electrospray ionization nozzles, filters and flow sensors), the
      integration of these different devices can potentially lead to versatile and
      functional micro total analysis systems (microTAS).

PMID- 15472735
TI  - Planar lipid bilayer reconstitution with a micro-fluidic system.
AB  - A planar lipid bilayer which is widely used for the electrophysiological study of
      membrane proteins in laboratories is reconstituted using a micro-fluidic system,
      in a manner that is suitable for automated processing. We fabricated micro
      channels on both sides of the substrate, which are connected through a 100-200
      microm aperture, and showed that the bilayer can be formed at the aperture by
      flowing the lipid solution and buffer, alternately. Parylene coating is found to
      be suitable for both bilayer formation and electric noise reduction. Future
      applications include a high-sensitivity ion sensor chip and a high-throughput
      drug screening device.

PMID- 15472736
TI  - Sequential DNA hybridisation assays by fast micromixing.
AB  - The prospects of performing DNA hybridisation assays in a novel sequential scheme
      are explored in this article. It is based on recording the kinetics of
      hybridisation on a microfluidic device measuring only 10 by 5 mm. It contains a
      split channel system for fast mixing and a subsequent meandering channel to
      observe the evolution of the mixture by optical means. The problems of diffusion
      limitations in the laminar flow regime are overcome by reducing the average
      diffusion distance to a few micrometers only. DNA oligomers (20-mers) of
      different sequences were injected on the chip for mixing. The detection of
      hybridisation was based on the fluorescence of DNA-intercalating dyes. Two modes
      of operation were investigated. First, the samples were injected into the
      micromixing device at a high flow rate of 40 microl min(-1). When the sample
      passed through the actual micromixing unit, the flow rate was reduced to allow
      for measurement of fluorescence levels at various steady-state reaction times in
      the range of 2-15 s, as defined by the channel geometry. Using this continuous
      flow approach, photobleaching of fluorophores could be avoided. In a buffer
      containing 0.2 M NaCl, 2 base-pair mismatches could routinely be detected within
      5-20 s. Single base-pair mismatches were successfully identified under low salt
      conditions. In the second mode, the flow was completely stopped and the evolution
      of the total fluorescence signal influenced by the hybridisation of oligomers and
      photobleaching was observed. Whereas the sequence-dependent effects remained
      unchanged, the assay times between the mixing of two oligomers and clear
      identification of their hybridisation properties could be reduced down to a
      maximum of 5-7 s, in some cases even below 1 s.

PMID- 15472737
TI  - A flexible sample introduction method for polymer microfluidic chips using a
      push/pull pressure pump.
AB  - A push/pull sample introduction method based on push/pull pressure flow for
      microfluidic systems (cross, double T and multichannel structures) is presented.
      This leads to well-defined and controllable sample plugs even when dealing with
      long channels. By tuning the relative push/pull pressure, it is shown that the
      size of the sample plug can effectively be controlled. Good signal
      reproducibility upon continued sample introduction and subsequent chip
      electrophoresis employing fluorescence detection is demonstrated for different
      chip geometries (i.e. short channels and long channels). Since the performance of
      the method is relatively insensitive to chip geometry, it is particularly useful
      for polymeric prototype microchips as tedious optimization is not required.
      Furthermore, the push/pull sample introduction is extended to multichannel chips
      thus demonstrating the possibilities of applying the methodology for realizing
      single chip high throughput sample analysis.

PMID- 15472738
TI  - Cell lysis on a microfluidic CD (compact disc).
AB  - Cell lysis was demonstrated on a microfluidic CD (Compact Disc) platform. In this
      purely mechanical lysis method, spherical particles (beads) in a lysis chamber
      microfabricated in a CD, cause disruption of mammalian (CHO-K1), bacterial
      (Escherichia coli), and yeast (Saccharomyces cerevisiae) cells. Interactions
      between beads and cells are generated in the rimming flow established inside a
      partially filled annular chamber in the CD rotating around a horizontal axis. To
      maximize bead-cell interactions in the lysis chamber, the CD was spun forward and
      backwards around this axis, using high acceleration for 5 to 7 min. Investigation
      on inter-particle forces (friction and collision) identified the following
      parameters; bead density, angular velocity, acceleration rate, and solid volume
      fraction as having the most significant contribution to cell lysis. Cell
      disruption efficiency was verified either through direct microscopic viewing or
      measurement of the DNA concentration after cell lysing. Lysis efficiency relative
      to a conventional lysis protocol was approximately 65%. In the long term, this
      work is geared towards CD based sample-to-answer nucleic acid analysis which will
      include cell lysis, DNA purification, DNA amplification, and DNA hybridization
      detection.

PMID- 15472739
TI  - Advances in biomedical image analysis--past, present and future challenges.
AB  - Starting from raw data files coding eight bits of gray values per image pixel and
      identified with no more than eight characters to refer to the patient, the study,
      and technical parameters of the imaging modality, biomedical imaging has
      undergone manifold and rapid developments. Today, rather complex protocols such
      as Digital Imaging and Communications in Medicine (DICOM) are used to handle
      medical images. Most restrictions to image formation, visualization, storage and
      transfer have basically been solved and image interpretation now sets the focus
      of research. Currently, a method-driven modeling approach dominates the field of
      biomedical image processing, as algorithms for registration, segmentation,
      classification and measurements are developed on a methodological level. However,
      a further metamorphosis of paradigms has already started. The future of medical
      image processing is seen in task-oriented solutions integrated into diagnosis,
      intervention planning, therapy and follow-up studies. This alteration of
      paradigms is also reflected in the literature. As German activities are strongly
      tied to the international research, this change of paradigm is demonstrated by
      selected papers from the German annual workshop on medical image processing
      collected in this special issue.

PMID- 15472740
TI  - Automated hybrid TACT volume reconstructions.
AB  - OBJECTIVES: To design, implement in Java, and evaluate a method and means for the
      automated localization of artificial landmarks in optical images for tuned
      aperture computed tomography (TACT) that allows the replacement of radiographic
      with optical landmarks. METHODS: Circular, colored, optical landmarks were
      designed to provide flexibility with regard to landmark constellation, imaging
      equipment, and lighting conditions. The landmark detection was based on Hough
      transforms (HT) for ellipses and lines. The HT for ellipses was extended to
      enable selective detection of bright ellipses on a dark background and vice
      versa, and the number of irrelevant votes in the accumulator arrays was reduced.
      An experiment was performed in vitro to test the automated landmark localization
      scheme, verify registration accuracy, and measure the required computation time.
      RESULTS: A visual evaluation of the tomographic slices that were produced using
      the new method revealed good registration accuracy. A comparison to tomographic
      slices similarly produced by means of conventional TACT showed identical results.
      The algorithm ran sufficiently fast on standard hardware to allow landmark
      localization in "real time" during successive image acquisition in clinical
      applications. CONCLUSIONS: The proposed method provides robust automated
      localization of landmarks in optical images. Using a hybrid imaging system, TACT
      can now be clinically applied without manual interaction of a human operator and
      without radiopaque landmarks, which might cover anatomic details of diagnostic
      interest.

PMID- 15472741
TI  - A linear programming approach to limited angle 3D reconstruction from DSA
      projections.
AB  - OBJECTIVES: We investigate the feasibility of binary-valued 3D tomographic
      reconstruction using only a small number of projections acquired over a limited
      range of angles. METHODS: Regularization of this strongly ill-posed problem is
      achieved by (i) confining the reconstruction to binary vessel/non-vessel
      decisions, and (ii) by minimizing a global functional involving a smoothness
      prior. RESULTS: Our approach successfully reconstructs volumetric vessel
      structures from three projections taken within 90 degrees. The percentage of
      reconstructed voxels differing from ground truth is below 1%. CONCLUSION: We
      demonstrate that for particular applications--like Digital Subtraction
      Angiography--3D reconstructions are possible where conventional methods must
      fail, due to a severely limited imaging geometry. This could play an important
      role for dose reduction and 3D reconstruction using non-conventional technical
      setups.

PMID- 15472742
TI  - Intensity-based image registration with a guaranteed one-to-one point match.
AB  - OBJECTIVES: In this paper, we propose a novel registration technique, which
      combines the concepts of landmark and automatic, non-rigid intensity-based
      approaches. A general framework, which might be used for many different
      registration problems is presented. The novel approach enables the incorporation
      of different distance measures as well as different smoothers. METHODS: The
      proposed scheme minimizes a regularized distance measure subject to some
      interpolation constraints. The desired deformation is computed iteratively using
      an Euler-scheme for the first variation of the chosen objective functional.
      RESULTS: A fast and robust numerical scheme for the computation of the wanted
      minimizer is developed, implemented, and applied to various registration tasks.
      This includes the registration of pre- and post-intervention images of the human
      eye. CONCLUSIONS: A novel framework for a parameter-free, non-rigid registration
      scheme which allows for the additional incorporation of user-defined landmarks is
      proposed. It enhances the reliability of conventional approaches considerably and
      thereby their acceptability by practitioners in a clinical environment.

PMID- 15472743
TI  - Accurate volumetric measurements of anatomical cavities.
AB  - OBJECTIVES: The volumetric assessment of anatomical cavities is of high relevance
      for various applications in medicine. Based on 3D scanning (i.e., CT) of these
      cavities, the volume can be determined by counting the volume elements of a
      segmentation of that cavity. Unfortunately, elements on the boundary of the
      segmentation require special treatment to obtain accurate volumetric
      measurements. In this paper, we propose a novel technique that in particular
      increases the accuracy of the volume estimation for the boundary elements of
      segmented anatomical objects. METHODS: Based on a 3D segmentation of an
      anatomical cavity, we recursively subdivide boundary volume elements into a set
      of simple situations, where the volume can be estimated easily. RESULTS: We
      performed volumetric measurements on seven datasets of phantom models made of
      plexiglass (see Fig. 1) scanned by a biplane angiography unit and assessed the
      quality of our method by comparing the measured volume by our novel method and by
      the fluid required to fill the phantom cavities. CONCLUSIONS: Our method
      calculates a significantly more accurate volume of the segmented cavities than
      previous methods. Nevertheless, it is only slightly more computationally
      expensive.

PMID- 15472744
TI  - Multimodal retinal image registration for optic disk segmentation.
AB  - OBJECTIVES: The analysis of the optic disk morphology with the means of the
      scanning laser tomography is an important step for glaucoma diagnosis. A method
      we developed for optic disk segmentation in images of the scanning laser
      tomograph is limited by noise, non-uniform illumination and presence of blood
      vessels. Inspired by recent medical research, we wanted to develop a tool for
      improving optic disk segmentation by registration of images of the scanning laser
      tomograph and color fundus photographs and by applying a method we developed for
      optic disk segmentation in color fundus photographs. METHODS: The segmentation of
      the optic disk for glaucoma diagnosis in images of the scanning laser tomograph
      is based on morphological operations, detection of anatomical structures and
      active contours and has been described in a previous paper. The segmentation of
      the optic disk in the fundus photographs is based on nonlinear filtering, Canny
      edge detector and a modified Hough transform. The registration is based on mutual
      information using simulated annealing for finding maxima. RESULTS: The
      registration was successful 86.8% of the time when tested on 174 images. Results
      of the registration have shown a very low displacement error of a maximum of
      about 5 pixels. The correctness of the registration was manually evaluated by
      measuring distances between the real vessel borders and those from the registered
      image. CONCLUSIONS: We have developed a method for the registration of images of
      the scanning laser tomograph and fundus photographs. Our first experiments showed
      that the optic disk segmentation could be improved by fused information from both
      image modalities.

PMID- 15472745
TI  - A semantic approach to segmentation of overlapping objects.
AB  - OBJECTIVES: This paper aims at introducing a novel approach for segmentation of
      overlapping objects and at demonstrating its applicability to medical images.
      METHODS: This work details a novel approach enhancing the known theory of full
      segmentation of an image into regions by lifting it to a semantic segmentation
      into objects. Our theory allows the formal description of partitioning an image
      into regions on the first level and allowing the occurrence of overlaps and
      occlusions of objects on a second, semantic level. Possible applications for the
      use of this 'semantical segmentation' are the analysis of radiographs and
      micrographs. We demonstrate our approach by the example of segmentation and
      separation of overlapping cervical cells and cell clusters on a set of 787 image
      pairs of registered PAP- and DAPI-stained micrographs. The semantical cell
      segmentation yielding areas of cell plasmas and nuclei are compared to a manual
      segmentation of the same images, where 2212 cells have been labeled. A direct
      comparison of over and under-segmentation between the two segmentation sets
      yields a mean difference value of 10.15% for the nuclei and 10.80% for the
      plasma. RESULTS: Using the proposed theory of semantical segmentation of images
      in combination with adequate models of the image contents, our approach allows
      identifying, separating and distinguishing several overlapping, occluding objects
      in medical images. Applying the proposed theory to the application of cervical
      cell segmentation from overlapping cell clusters and aggregates, it can be seen
      that it is possible to formally describe the complex image contents. CONCLUSIONS:
      The proposed method of semantical segmentation is a mighty tool and under the
      assumption of the subtractive transparency model can be used in different medical
      image processing applications such as radiology and microscopy. By using
      alternative models to solve the ambiguities attached to overlaps and occlusions,
      further fields of application can be addressed.

PMID- 15472746
TI  - Content-based image retrieval in medical applications.
AB  - OBJECTIVES: To develop a general structure for semantic image analysis that is
      suitable for content-based image retrieval in medical applications and an
      architecture for its efficient implementation. METHODS: Stepwise content analysis
      of medical images results in six layers of information modeling incorporating
      medical expert knowledge (raw data layer, registered data layer, feature layer,
      scheme layer, object layer, knowledge layer). A reference database with 10,000
      images categorized according to the image modality, orientation, body region, and
      biological system is used. By means of prototypes in each category,
      identification of objects and their geometrical or temporal relationships are
      handled in the object and the knowledge layer, respectively. A distributed system
      designed with only three core elements is implemented: (i) the central database
      holds program sources, processing scheme descriptions, images, features, and
      administrative information about the workstation cluster; (ii) the scheduler
      balances distributed computing; and (iii) the web server provides graphical user
      interfaces for data entry and retrieval, which can be easily adapted to a variety
      of applications for content-based image retrieval in medicine. RESULTS: Leaving
      one-out experiments were distributed by the scheduler and controlled via
      corresponding job lists offering transparency regarding the viewpoints of a
      distributed system and the user. The proposed architecture is suitable for
      content-based image retrieval in medical applications. It improves current
      picture archiving and communication systems that still rely on alphanumerical
      descriptions, which are insufficient for image retrieval of high recall and
      precision.

PMID- 15472747
TI  - Evaluation of computer-assisted image enhancement in minimal invasive endoscopic
      surgery.
AB  - OBJECTIVES: This paper focuses on the evaluation of the usage of computer-aided
      image processing methods for minimal invasive surgery. During video endoscopy of
      visceral cavities the images are displayed directly on the monitor without
      further processing. In the course of the operation the former good quality of the
      images decreases due to typical disturbances like bleeding, smoke or flying
      particles. These disturbances can be reduced by using image processing methods
      like color normalization, temporal filtering or equalization. METHODS: In this
      double-blinded analysis, 14 surgeons with different levels of experience
      evaluated 120 image pairs and 5 image sequences, directly comparing original and
      processed images or movies. RESULTS: Color normalization and equalization proved
      to significantly enhance video endoscopic images. With regard to temporal
      filtering, an improvement could be seen in the image sequences with filter size 5
      being a greater enhancement than filter size 3. Comparing the state of experience
      and its influence on the results, it occurred that the experienced surgeons
      preferred the original color while altogether agreeing that the color-normalized
      images were better. CONCLUSIONS: The results obtained in the present evaluation
      show that the image processing methods which were used can significantly improve
      the quality of video endoscopic images. As a result of this, necessary lavages of
      the operated area are reduced and a better overview and orientation for the
      surgeon can be reached.

PMID- 15472748
TI  - Objective evaluation of three-dimensional image registration algorithms--tools
      for optimization and evaluation.
AB  - OBJECTIVE: The registration of medical volume data sets plays an important role
      when different images or modalities are used during computer-assisted surgical
      procedures. Nevertheless, it is often questionable how robust and accurate the
      underlying algorithms really are. Therefore, the goal is to foster the
      establishment of methods for an objective evaluation. METHOD: To reliably
      calculate the accuracy of registration algorithms, a reference transformation
      must be known. Due to the unknown perfect registration for real clinical data,
      the simulation of realistic data and successive affine transformations are
      employed. The simulation is based on models of the respective imaging modality
      where the dominant physical effects are taken into account. This gives the user
      full control over all simulation and transformation parameters. Finally, suitable
      quality measures are applied which allow a systematic evaluation of image
      registration accuracy by comparing the known theoretical result and the
      transformation calculated by the algorithm under investigation. RESULTS: During
      the development of a new registration algorithm, the presented method proved to
      be a very valuable tool for optimization and evaluation of registration accuracy,
      since it allows objective numerical comparison of the calculated results.
      CONCLUSIONS: The presented method can be used during the development of
      algorithms for optimization and for quantitative comparison of different
      registration schemes. The respective software tool can automatically generate and
      transform simulated but realistic data. Employing suitable numerical quality
      measures, an objective evaluation of registration results can be easily obtained.
      Still, the validity of the relatively simple models has to be verified to draw
      reliable conclusions with respect to real data.

PMID- 15472749
TI  - Live-wires using path-graphs.
AB  - OBJECTIVES: This article discusses our new Path-Graph approach for the
      interactive Live-Wire segmentation method in 2D applied to pre-segmented data.
      Furthermore, we examine whether or not the Live-Lane extension provides
      advantages in combination with pre-segmentation. METHODS: We automatically over
      segment the image data in a preprocessing step, using region growing with an
      automatic seed point generation. The Live-Wire algorithm is applied on this
      mosaic data by using the outlines of the homogeneous regions as the basis for
      graph building. We present a new definition of this underlying graph where the
      edges of the standard graphs are turning into vertices and the vertices of the
      new graph are defined by the edge connectivity in the standard graph. For better
      differentiation we name our new graph Path-Graph and the original defined graph
      Node-Graph. RESULTS: The quality evaluation is done by comparing our segmentation
      results with existing model data. We show that using the Path-Graph as basis for
      the Live-Wire algorithm instead of the Node-Graph allows for a finer
      segmentation. We achieve a reduction of incorrectly classified pixels by 20.66
      per cent and a decrease of the mean boundary deviation by 11.61 per cent. Since
      savings on cost tree calculations are compensated by additional computation time
      required to compute the Live-Lanes, a performance loss of 2.41 per cent is
      measured. CONCLUSIONS: Our redefinition of the underlying graph increases the
      quality of the Live-Wire segmentation. The Live-Lane extension in combination
      with pre-segmentation is not justified for our data.

PMID- 15472750
TI  - A reliable and efficient method for cerebral ventricular volumetry in pediatric
      neuroimaging.
AB  - OBJECTIVES: Cerebral ventricular volume has the potential to become an important
      parameter in quantitative neurological diagnosis. However, no accepted
      methodology for routine clinical use exists to date. We sought a robust,
      reproducible, and fast technique to evaluate cerebral ventricular volume in young
      children. METHODS: We describe a novel volumetric methodology to segment and
      visualize intracerebral fluid spaces and to quantify ventricular volumes. The
      method is based on broadly available T1 weighted volumetric magnetic resonance
      (MR) imaging, an interactive watershed transform, and a fully automated histogram
      analysis. We evaluated this volumetric methodology with 34 clinical volumetric MR
      datasets from non-sedated children (age 6-7 y) with a history of prematurity and
      low birth weight (< or = 1500 g) obtained during a prospective study. RESULTS:
      The methodology, with adaptation for small ventricular size, was capable of
      evaluating all 34 of the pediatric datasets for cerebral ventricular volume. The
      method was a) robust for normal and pathological anatomy, b) reproducible, c)
      fast with less than five minutes for image analysis, and d) equally applicable to
      children and adults. CONCLUSIONS: Clinical brain ventricular volume calculations
      in non-sedated children can be performed using routine MR imaging besides
      efficient three-dimensional segmentation and histogram analysis with results that
      are robust and reproducible.

PMID- 15472751
TI  - MRI-based individual 3D region-of-interest atlases of the human brain: a new
      method for analyzing functional data.
AB  - OBJECTIVES: Introduction of a new atlas-based method for analyzing functional
      data which takes into account the variability of individual human brains and the
      partial volume, effects of functional emission computed tomography, images in
      complex anatomical 3D regions, as well as, describing the underlying multi-modal
      image processing, principles. METHODS: 3D atlas extraction is done directly by
      automated segmentation of individual magnetic resonance images of the patient's
      head. This is done in two steps: voxel-based classification of T1-weighted images
      for tissue differentiation (low-level processing) is followed by knowledge-based
      analysis of the classified images for extraction of 3D anatomical regions (high
      level processing). For atlas-based quantification of co-registered functional
      images, 3D anatomical regions can be convoluted with an idealized point spread
      function of the emission computed tomography system, after which a partial volume
      dependent threshold can be determined. RESULTS: Quantitative evaluation studies,
      based on 50 realistic software head phantoms and 24 image data sets obtained from
      healthy subjects and patients, show low misclassification rates and stable
      results for the neural network-based classification approach (mean +/- SD 3.587
      +/- 0.466%, range 2.726-4.927%) as well as for the adjustable parameters of the
      knowledge-based approach. Computation time is <5 min for classification, <1 min
      for most of the extraction algorithms. The influence of the partial volume
      dependent threshold is shown for an activation study. CONCLUSIONS: This new
      method allows 3D atlas generation without the need to warp individual image data
      to an anatomical or statistical brain atlas. Going beyond the purely tissue
      oriented approach, partial volume effects of emission computed tomography images
      can be analyzed in complex anatomical 3D regions.

PMID- 15472752
TI  - Atlas-based recognition of anatomical structures and landmarks and the automatic
      computation of orthopedic parameters.
AB  - OBJECTIVE: This paper describes methods for the automatic atlas-based
      segmentation of bone structures of the hip, the automatic detection of anatomical
      point landmarks and the computation of orthopedic parameters to avoid the
      interactive, time-consuming pre-processing steps for the virtual planning of hip
      operations. METHODS: Based on the CT data of the Visible Human Data Sets, two
      three-dimensional atlases of the human pelvis have been built. The atlases
      consist of labeled CT data sets, 3D surface models of the separated structures
      and associated anatomical point landmarks. The atlas information is transferred
      to the patient data by a non-linear gray value-based registration algorithm. A
      surface-based registration algorithm was developed to detect the anatomical
      landmarks on the patient's bone structures. Furthermore, a software tool for the
      automatic computation of orthopedic parameters is presented. Finally, methods for
      an evaluation of the atlas-based segmentation and the atlas-based landmark
      detection are explained. RESULTS: A first evaluation of the presented atlas-based
      segmentation method shows the correct labeling of 98.5% of the bony voxels. The
      presented landmark detection algorithm enables the precise and reliable
      localization of orthopedic landmarks. The accuracy of the landmark detection is
      below 2.5 mm. CONCLUSION: The atlas-based segmentation of bone structures, the
      atlas-based landmark detection and the automatic computation of orthopedic
      measures are suitable to essentially reduce the time-consuming user interaction
      during the pre-processing of the CT data for the virtual three-dimensional
      planning of hip operations.

PMID- 15472753
TI  - Registration of biplane angiography and intravascular ultrasound for 3D vessel
      reconstruction.
AB  - If planned and applied correctly, intra-vascular brachytherapy (IVB) can
      significantly reduce the risk of restenosis after interventional treatment of
      stenotic arteries. OBJECTIVES: In order to facilitate computer-based IVB
      planning, a three-dimensional reconstruction of the stenotic artery based on
      intravascular ultrasound (IVUS) sequences is desirable. METHODS: To attain a 3D
      reconstruction, the frames of the IVUS sequence are properly aligned in space and
      completed with additional intermediate frames generated by interpolation. The
      alignment procedure uses additional information that is obtained from biplane X
      ray angiography performed simultaneously during the capturing of the IVUS
      sequence. After IVUS images and biplane angiography data are acquired from the
      patient, the vessel-wall borders and the IVUS catheter are detected by an active
      contour algorithm. Next, the twist between adjacent IVUS frames is determined by
      a sequential triangulation method combined with stochastic analysis. RESULTS: The
      above procedure results in a 3D volume-model of the vessel, which also contains
      information from the IVUS modality. This data is sufficient for computer-based
      intravascular brachytherapy planning. CONCLUSION: The proposed methodology can be
      used to improve the current state-of-the-art IVB treatment planning by enabling
      computerized dosage computations on a highly accurate 3D model.

PMID- 15472754
TI  - Light fields for minimal invasive surgery using an endoscope positioning robot.
AB  - OBJECTIVES: To generate a fast and robust 3-D visualization of the operation site
      during minimal invasive surgery. METHODS: Light fields are used to model and
      visualize the 3-D operation site during minimal invasive surgery. An endoscope
      positioning robot provides the position and orientation of the endoscope. The a
      priori un-known transformation from the endoscope plug to the endoscope tip (hand
      eye transformation) can either be determined by a three-step algorithm, which
      includes measuring the endoscope length by hand or by using an automatic hand-eye
      calibration algorithm. Both methods are described in this paper and their
      respective computation times and accuracies are compared. RESULTS: Light fields
      were generated during real operations and in the laboratory. The comparison of
      the two methods to determine the unknown hand-eye transformation was done in the
      laboratory. The results which are being presented in this paper are: rendered
      images from the generated light fields, the calculated extrinsic camera
      parameters and their accuracies with respect to the applied hand-eye calibration
      method, and computation times. CONCLUSION: Using an endoscope positioning robot
      and knowing the hand-eye transformation, the fast and robust generation of light
      fields for minimal invasive surgery is possible.

PMID- 15472755
TI  - Establishing an international reference image database for research and
      development in medical image processing.
AB  - INTRODUCTION: The lack of comparability of evaluation results is one of the major
      obstacles of research and development in Medical Image Processing (MIP). The main
      reason for that is the usage of different image datasets with different quality,
      size and Gold standard. OBJECTIVES: Therefore, one of the goals of the Working
      Group on Medical Image Processing of the European Federation for Medical
      Informatics (EFMI WG MIP) is to develop first parts of a Reference Image
      Database. METHODS: Kernel of the concept is to identify highly relevant medical
      problems with significant potential for improvement by MIP, and then to provide
      respective reference datasets. The EFMI WG MIP has primarily the role of a
      specifying group and an information broker, while the provider user relationships
      are defined by bilateral co-operation or license agreements. RESULTS: An
      explorative database prototype has been implemented using the MySQL database
      software on the Web. Templates for provider user agreements have been worked out
      and already applied for own 'pre-RID-MIP' co-operations of the authors.
      DISCUSSION AND CONCLUSION: First steps towards a comprehensive reference image
      database have been done. Issues like funding, motivation, management, provision
      of Gold standards and evaluation guidelines are to be solved. Due to the interest
      from research groups and industry the efforts will be continued.

PMID- 15472756
TI  - HELEN, a modular framework for representing and implementing clinical practice
      guidelines.
AB  - OBJECTIVES: In order to implement clinical practice guidelines for the Department
      of Neonatology of the Heidelberg University Medical Center we developed a modular
      framework consisting of tools for authoring, browsing and executing encoded
      clinical practice guidelines (CPGs). METHODS: Based upon a comprehensive analysis
      of literature, we set up requirements for guideline representation systems.
      Additionally, we analyzed further aspects such as the critical appraisal and
      known bridges and barriers for implementing CPGs. Thereafter we went through an
      evolutionary spiral model to develop a comprehensive ontology. Within this model
      each cycle focuses on a certain topic of management and implementation of CPGs.
      RESULTS: In order to bring the resulting ontology into practice we developed a
      framework consisting of a tool for authoring, a server for web-based browsing,
      and an engine for the execution of certain elements of CPGs. Based upon this
      framework we encoded and implemented several CPGs in varying medical domains.
      CONCLUSIONS: This paper shall present a practical framework for both authors and
      implementers of CPGs. We have shown the fruitful combination of different
      knowledge representations such as narrative text and algorithm for implementing
      CPGs. Finally, we introduced a possible approach for the explicit adaptation of
      CPGs in order to provide institution-specific recommendations and to support
      sharing with other medical institutions.

PMID- 15472757
TI  - An approach to knowledge base construction based on expert opinions.
AB  - OBJECTIVES: To describe, validate and demonstrate an approach for knowledge base
      construction based on expert opinions. METHODS: A knowledge base containing the
      frequency of occurrence of manifestations in epileptic seizures is constructed
      based on information provided by neurologists/epileptologists. The reliability of
      the responses is determined with the inter-rater intraclass correlation
      coefficient (ICC). If the ICC is not large enough the Spearman-Brown prophecy
      formula can be used to predict the number of additional experts. We propose a
      method to assess whether an additional expert provides information consistent
      with the already acquired data as well as a method to detect experts with
      deviating opinions. The power of the first method was determined. RESULTS: Data
      were collected for five seizure types. The ICCs determined from the responses for
      the various seizure types after inclusion of the additional experts was in all
      cases almost equal to 0.9, the target value. Yet one expert with diverging
      opinions concerning the frequency of occurrence of manifestations for different
      seizure types could be identified. Excluding this participant improved the
      reliability of the data. The power of the methods was good (> or =0.75).
      CONCLUSIONS: It is shown that human experts can provide reliable information
      about the frequency of occurrence of manifestations in epileptic seizures. In
      addition, the described approach correctly identified
      neurologists/epileptologists with both consistent and diverging opinions about
      the frequency of occurrence of manifestations in a number of seizure types.

PMID- 15472758
TI  - [Importance of orthopedics].

PMID- 15472759
TI  - [Before the annual meeting of the German Orthopedic Societies 2004].

PMID- 15472760
TI  - [Cartilage is sturdier--progress in autologous chondrocyte transplantation].

PMID- 15472761
TI  - [Indications and implementation of recommendations of the working group "Tissue
      Regeneration and Tissue Substitutes" for autologous chondrocyte transplantation
      (ACT)].
AB  - For the treatment of full-thickness articular cartilage lesions of the knee
      joint, as a result of trauma or osteochondritis dissecans, a variety of
      biological reconstruction techniques have been developed. Different studies, some
      of which were performed as randomised, prospective clinical studies, showed that
      the autologous chondrocyte transplantation (ACT) provides the most satisfying and
      reliable method of cartilage reconstruction in the adult when applied to defects
      exceeding 4 cm (2). Based on these results, ACT seems to be of economic benefit,
      as the risk of developing osteoarthritis correlates significantly with the size
      of the cartilage defect, when not treated properly and in time. Surveying the
      studies on basic scientific aspects of ACT, cartilage defect animal models and
      clinical studies, it can be concluded that clinical results of ACT depend on a
      variety of factors. In this review, published by the joined advisory board of the
      German Societies of Traumatology (DGU) and Orthopaedic Surgery (DGOOC), we
      summarize the current knowledge available and the state of the art concerning
      ACT. Especially we discuss the advantages of different procedures, methods for
      treating knee cartilage defects and factors that influence the outcome of the
      different treatment regimens, with the aim to develop guidelines for the correct
      indication and application of the ACT.

PMID- 15472762
TI  - [Meniscus replacement: current aspects in the field of tissue engineering].
AB  - Tissue engineering offers new opportunities for meniscus repair and replacement.
      In this field different approaches are being studied to genererate a meniscus
      subsitute by a combination of a matrix scaffold, cells and specific stimuli.
      MENISCUS REPLACEMENT BY ACELLUAR MATRICES: For meniscus replacement the matrix
      material has to meet high biomechanical demands. Besides implant geometry, the
      material properties and a secure intraarticular attachment are important
      preconditions for implant function. A collagen scaffold has already been applied
      clinically for partial meniscus replacement. Scaffolds made of synthetic,
      bioabsorbable polymers and small intestine submucosa have been employed in animal
      studies. Following implantation, matrices are invaded by cells and undergo a
      process of remodeling. Formation of fibrocartilage repair tissue has been
      observerd. The biomechanical quality of implants and their effect on cartilage
      preservation have to be studied further. CELLULAR SEEDING OF MATRICES FOR
      MENSICUS REPLACEMENT: Advanced biological and biomechanical implant quality might
      be achieved by seeding matrices with cells in vitro. However, the ideal type of
      cell for this purpose has not yet been identified. Autologous mensicus cells,
      articular chondrocytes and mesenchymal stem cells represent possible cellular
      sources. Additional stimuli, such as cytokines and mechanical forces, and
      techniques of genetic engineering might further contribute to enhance the quality
      of engineered tissue.

PMID- 15472763
TI  - [Current treatment modalities for cartilage defects at the knee--results of a
      nation-wide survey of surgical trauma and orthopaedic clinics in Germany].
AB  - AIM: A local cartilage defect at the knee is mostly followed by arthritis after a
      period of time. Up to now there are no options to adequately regenerate hyaline
      cartilage in vivo. Hence, the present strategies try to create a repair tissue
      with hyaline-like characteristics or to repair defects by transplanting
      autologous osteochondral cylinders. The objective of this study was to collect
      data about the current treatment of local cartilage defects of the knee in
      Germany. METHOD: In a countrywide anonymous survey, 250 German trauma surgery and
      220 orthopaedic surgery departments were asked about their diagnostic procedures
      and their treatment strategies when addressing a local cartilage defect of the
      knee. RESULTS: 230 (48.9 %) of the questionnaires were returned and evaluated. We
      found differences between the two specialities: the orthopaedic departments are
      more progressive in applying autologous chondrocyte transplantation (ACT) (28.3 %
      versus 13.6 %) and osteochondral transplantation (OCT) (69.1 % versus 56.3 %).
      Only 5.2 % of the German surgeons perform periostal grafting for local cartilage
      defects. CONCLUSION: There are still discrepancies about the therapy for local
      cartilage defects of the knee. Our survey illustrates the present status of
      cartilage repair strategies in Germany.

PMID- 15472764
TI  - [Therapy of femoral head osteonecrosis: results of a national survey].
AB  - AIM: The therapy for osteonecrosis (ON) of the femoral head is controversially
      discussed in the literature. The aim of this study was to ascertain the current
      treatment concepts of ON in Germany and to compare them with the results reported
      in the literature. METHODS: 219 Departments of Orthopedic Surgery were asked for
      their treatment strategies in an anonymous country-wide survey regarding the
      etiology, diagnosis and therapy (conservative, operative) of ON. Univariate
      analyses were performed and means, medians and rates were calculated. RESULTS: 43
      % of ON were idiopathic, 28 % were due to alcoholism and another 17 % were seen
      after steroid intake. All departments performed biplanar X-rays for diagnosis of
      ON and 78 % of departments obtained additional magnet resonance imaging. In the
      early stages of ON (stage I, II) 33 % of orthopedic clinics recommend a
      conservative treatment (protected weight bearing, high energy shock wave, pulsed
      electromagnetic fields) while 67 % prefer surgery (79 % core decompression, 15 %
      flexion osteotomy, 6 % total hip arthroplasty). In the later stages (stage III,
      IV) most clinics perform an operative treatment (11 % core decompression, 10 %
      flexion osteotomy, 79 % total hip arthroplasty). CONCLUSION: Results of ON of the
      femoral head are unsatisfactory after protected weight bearing. No randomized
      clinical trials and no mid-term results are available for high energy shock wave
      or pulsed electromagnetic fields therapy. In the early stages of ON core
      decompression shows good results. However, in he later stages with secondary
      arthritis of the hip, total hip arthroplasty remains the gold standard.

PMID- 15472765
TI  - [Reimplantation of the artificial hip joint in girdlestone hips is superior to
      girdlestone arthroplasty by itself].
AB  - AIM: The aim of this work was to compare the functional results of secondary
      Girdlestone hips with the results of total hip replacement (THR) after a
      Girdlestone situation. METHODS: 72 patients with THR following a Girdlestone
      situation and 87 patients with a Girdlestone situation (90 hips) were compared
      with regard to defined endpoints. RESULTS: THR following a Girdlestone situation
      provided for significantly higher patient satisfaction (89 % versus 13 %) and hip
      function (HHS 63 versus 39 points). The groups only marginally differed with
      regard to the incidence of complications (0.32 versus 0.26 per patient) and the
      necessity for surgical revision (0.38 versus 0.31 per patient). CONCLUSION:
      Conversion of Girdlestone hips with THR provided patient satisfaction and
      functional results superior to secondary Girdlestone hips while the incidence of
      postoperative complications and revisions were similar for both groups. These
      differences justify attempts at the conversion of Girdlestone situations with
      THR, if technically possible, in accordance with the patient's wish and as
      allowed by his/her general health.

PMID- 15472766
TI  - [Risk factors associated with heterotopic ossifications in primary total hip
      arthroplasty].
AB  - AIM: The purpose of this study was to determine the important predisposing
      factors associated with heterotopic ossifications (HO) after total hip
      arthroplasty. METHOD: 589 patients were examined 6 months after primary total hip
      arthroplasty with regard to periarticular ossifications. Several predetermining
      factors were evaluated using the hospitalization records and preoperative X-ray
      examination. RESULTS: A significantly increased frequency of heterotopic
      ossifications was found for male gender, patients with very high body mass index
      (BMI), low preoperative range of motion (ROM), long duration of operation and
      large preexistent osteophytes (p < 0.05). Only one out of the one hundred
      patients with an BMI < 22.6 developed severe HO (Brooker III). Out of the one
      hundred patients with the best preoperative ROM (> or = 140 degrees ) only one
      case developed severe ossifications (Brooker III). There was no correlation with
      the use of acrylic bone cement or the patient's age. The frequency of HO was
      significantly reduced both as well by nonsteroidal antiinflammatory drugs as from
      postoperative radiation prophylaxis. CONCLUSION: In patients undergoing total hip
      arthroplasty with low preoperative ROM in the hip joint, large osteophytes and a
      very high BMI an efficient prophylaxis against HO is of great importance.

PMID- 15472767
TI  - [Usefulness of 16S rDNA polymerase-chain-reaction (PCR) in the intraoperative
      detection of infection in revision of failed arthroplasties].
AB  - AIM: In this study the accuracy of the 16S DNA polymerase chain reaction (PCR) in
      revision arthroplasties was compared to that of conventional bacterial culture
      when correlated to intraoperative histological findings. Furthermore, the
      influence of antibiotic treatment and different ways of collecting samples was
      evaluated. METHOD: In a prospective study we collected samples of tissues,
      aspiration fluids and swabs during revision arthroplasty surgery and examined
      them with PCR as well as conventional bacterial culturing methods. Also, we
      correlated these two methods with the histological findings of intraoperative
      tissue samples. Two independent examiners evaluated the samples according to the
      criteria of Mirra et al. Sensitivity, specificity, positive and negative
      prediction value and the accuracy were calculated for the molecular biological
      and culture methods. Three groups were defined to evaluate the influence of
      accompanying antibiotic treatment and the way of collecting the microbiological
      samples. RESULTS: Nine periprosthetic infections could be detected by PCR as well
      as by conventional bacterial culturing. Correlated with the 25 positive
      histological findings this resulted in a sensitivity of 0.36, a specificity of
      1.0, a negative prediction value of 0.61, a positive prediction value of 1.0 and
      an accuracy of 0.68 for both methods. Swabs compared to aspiration fluids and
      tissues samples showed the highest sensitivity with both methods. No higher
      sensitivity of PCR compared to conventional bacterial culturing could be observed
      in patients with accompanying antibiotic treatment. CONCLUSION: Although PCR is
      more rapidly available for the diagnosis of periprosthetic infection, a definite
      advantage of this more expensive method could not be demonstrated in view of the
      same low sensitivity of PCR and conventional bacterial culturing.

PMID- 15472768
TI  - [Experimental analysis of neutral, asymmetric and constraint liners for total hip
      replacement: investigation of range of motion and protection against joint
      instability].
AB  - AIM: Recurrent dislocation after total hip replacement is a severe complication,
      which requires specific treatment and implants. The purpose of the present study
      was to compare a constraint liner with an elevated rim and standard liner
      regarding their range of motion and dislocation stability. METHOD: With a test
      device, range of motion until impingement (ROM (Imp)) and dislocation (ROM (Lux))
      were experimentally analyzed using the above-mentioned insert types of a
      commercial total hip system. On the basis of movement combinations associated
      with dislocation, the ROM was determined. Further measuring parameter was the
      resisting moment against subluxation of the femoral head. RESULTS: The constraint
      liners showed clear restriction of the movements "internal rotation combined with
      90 degrees flexion and 0 degrees adduction" and "external rotation with 10
      degrees extension and 15 degrees adduction" of up to 20 degrees compared to the
      neutral liner. ROM (Imp) was only decreased by about 8 degrees with the elevated
      rim liner. The constraint liners revealed the highest resisting moments in
      subluxation, however, at adequate orientation in the acetabular cup the elevated
      rim liners provided a higher ROM (Lux) of up to 12 degrees. Both designs were
      superior to the neutral liner at retroversion and steep cup position regarding
      resisting moment and ROM (Lux). CONCLUSION: In case of insufficient soft tissue
      tension the use of constraint liners may increase the dislocation stability,
      however, in contrast to elevated-rim liners the impingement-free movement
      interval is clearly reduced. Thus, material damage and high shear stress in the
      bone interface can result. Therefore, constraint liners should only be used in
      exceptional cases.

PMID- 15472769
TI  - [MRI after reconstruction of the supraspinatus tendon: MR-tomographic findings].
AB  - AIM: The value of MRI for pre-operative evaluation of the rotator cuff is proven.
      In spite of its clinical relevance, there have been only few studies on MR
      imaging of patients who have already been operated. Thus, the question rises to
      what extent the post-operative MRI can contribute to the evaluation of the
      integrity of the rotator cuff. METHOD: At least 10 months after successful open
      repair of the supraspinatus tendon, mostly combined with Neer's anterior
      acromioplasty, an MR scan was performed on 33 shoulders. Only patients satisfied
      with the outcome of surgery and showing a Constant score of 65 to 100 points were
      included. RESULTS: More than half the patients had positive direct diagnostic
      criteria for a full- or partial-thickness tear of the supraspinatus tendon, in
      the form of signal intensity or morphological alterations. In addition, the
      indirect diagnostic criteria described by Zlatkin, such as the absence of the
      subacromial-subdeltoid fat or the appearance of subacromial-subdeltoid fluid,
      were often positive. Atrophy of the supraspinatus muscle, as a further indirect
      diagnostic criterion of a rupture, was also frequently noted. CONCLUSION: Taking
      the excellent clinical outcome of our patients into consideration, this study
      shows that caution should be taken in evaluating postoperative MR images. There
      is a high risk of over-interpreting MR findings.

PMID- 15472770
TI  - [Evaluation of force and mobility following the open Bankart operation for
      treatment of recurrent dislocation of the shoulder].
AB  - AIM: The purpose of this study was to evaluate the isokinetic muscle strength,
      range of motion and radiological signs of arthopathy of recurrent dislocation of
      the shoulder after an open Bankart procedure. METHODS: This retrospective study
      is based on the analysis of isokinetic muscle strength, range of motion, function
      and arthropathy of the shoulders of 81 patients at an average of 2.3 years (range
      1-4 years) after a Bankart procedure. Isokinetic muscle strength testing was
      performed using the Cybex 6000 dynamometer. RESULTS: Clinical testing at follow
      up revealed no significant loss of range of motion of the operated shoulder
      compared to the healthy contralateral shoulder. The deficit of muscle strength
      (average peak torque, total work, total power) of the involved side averaged 10 %
      of the not-involved side and was not statistically different. Follow-up
      radiographs demonstrated an increase of arthropathy in 35 % of the shoulders
      after the Bankart procedure. CONCLUSION: At an average follow-up of 2.3 years
      after an open Bankart repair for treatment of recurrent dislocation of the
      shoulder we found no significant difference between the operated shoulder and the
      healthy contralateral side concerning range of motion and isokinetic muscle
      strength. From that we conclude that the Bankart procedure offers an excellent
      clinical outcome combined with a low degree of morbidity.

PMID- 15472771
TI  - [Effectiveness of interscalene plexus block for open subacromion decompression].
AB  - AIM: The aim of this study was to assess the influence of interscalene brachial
      plexus blocks on the functional outcome, subjective pain appraisal and patient
      satisfaction after open shoulder surgery. These results were compared with
      patients treated by conventional analgesic measures. METHOD: 23 patients with
      interscalene brachial plexus block (ISB) and 21 patients without ISB were
      evaluated preoperatively as well as 1, 7, 12 and 90 days after open surgery of
      the shoulder. By means of a visual analogue scale (VAS) subjective postoperative
      pain intensity was assessed. Using the Constant score preoperatively and 6 months
      after surgery the functional status of the treated shoulder was evaluated. At
      discharge from hospital patients were asked whether they were satisfied with the
      analgesic measures taken. RESULTS: The range of motion of the shoulder of
      patients treated with an ISB was significantly higher 1 and 7 days after surgery
      than those without ISB. 12 and 90 days postoperatively the range of motion in the
      ISB group was still higher, but no longer statistically significant. Assessment
      of the postoperative subjective pain status showed that patients with an ISB had
      significantly lower values and required less additional analgesia. In both groups
      the Constant score was significantly higher 6 months after surgery, compared to
      the preoperative condition. Compared to the control group, patients treated with
      ISB were clearly more satisfied with the postoperative pain management.
      CONCLUSION: By implementing ISB sufficient analgesia in the early postoperative
      period after open shoulder surgery is attained, allowing for early physiotherapy.
      This positively influences convalescence and the outcome of the surgical
      procedure. Furthermore, patients are visibly more satisfied with the
      postoperative pain management.

PMID- 15472772
TI  - [The effects of hook plates on the subacromial space--a clinical and MRT study].
AB  - AIM: The analysis of middle- and long-term results after treatment of
      acromioclavicular joint injuries with a hook plate as a temporary implant and a
      comparison of the results with those described in literature have been made.
      METHOD: In a retrospective study we were able to conduct follow-up examinations
      on 28 out of 39 Tossy III patients (72 %) who received surgical treatment using a
      hook plate according to Dreithaler. Examinations took place on average 3.0 (1.2
      5.6) years after surgery. A special focus of attention was the effect of the hook
      plate on the subacromial space. Accordingly, physical examination was
      supplemented by sonography of the shoulder as well as comparative bilateral
      shoulder MRI. RESULTS: 86 % of our patients expressed satisfaction with the
      functional outcome of surgery as opposed to 54 % concerning its cosmetic result.
      In shoulder sonography no patient turned out to have suffered a higher grade
      rotator cuff lesion, whereas age-related degenerative alterations were found in
      46 % of the patients. Instability under load was found in 7 patients (25 %).
      Among these were 3 with severe instability (11 %). 2 patients (7 %) were found to
      have a permanent subluxation of the acromioclavicular joint with partial range of
      motion impairment. All scores monitored (DASH, Taft, Constant-Murley) on average
      returned good to excellent results. MRI scans displayed no case of higher grade
      rotator cuff lesion. In accordance with the findings of ultrasound imaging a
      higher incidence of extraarticular ossification was found as well as, in some
      cases, arthrosis of the acromioclavicular joint. CONCLUSION: In our opinion, the
      hook plate designed by Dreithaler is easy to handle and serves as a qualified
      implant for temporary stabilisation of the acromioclavicular joint with middle-
      and long-term good to excellent results.

PMID- 15472773
TI  - [One-stage revision of shoulder arthroplasty in the case of periprosthetic
      infection].
AB  - AIM: Infection of shoulder arthroplasties is rare, but represents a potentially
      devastating complication. The aim of this work is to show the value of various
      diagnostic procedures, specify causative pathogens and present the results of one
      stage revised patients. METHOD: We performed a retrospective analysis of our 16
      consecutive patients with an infected shoulder arthroplasty. RESULTS: In 13 of 16
      cases a causative pathogen could be established preoperatively. Staphylococcus
      and Propioni spp. dominated. Only 9 patients could be followed up because two
      died, two were lost and three patients were revised because of non-infectious
      complications. The follow-up time was 5.8 years (13 months-13.25 years). The
      Constant-Murley score was 33.6 of 100. Eradication of infection was achieved in
      all patients. In the follow-up time no reinfection has occurred. CONCLUSION:
      Culturing of the preoperative joint fluid aspirate and the determination of CRP
      provide an early diagnosing of shoulder arthroplasty infection. One-stage
      revision arthroplasty with radical debridement and application of antibiotics to
      the bone cement provide an accurate therapy of periprosthetic shoulder infection.

PMID- 15472774
TI  - [Osteochondral lesions of the talus -- indications for MRI with a contrast
      agent].
AB  - AIM: This study aims to establish the indication for a pre- and postoperative MRI
      examination with an intravenous contrast agent in patients with an osteochondral
      lesion of the talus. METHODS: 20 patients with an osteochondral lesion of the
      talus in the different stages according to DiPaola were prospectively examined
      preoperatively and 6 months postoperatively by an MRI investigation with an i. v.
      contrast agent. The Weber ankle score was determined pre- and postoperatively. A
      correlation was calculated between MRI and arthroscopic findings of an
      osteochondral lesion (Spearman-rho). RESULTS: There was a significant correlation
      among the radiological, the MRI and the arthroscopically determined locations.
      With regard to staging only 12 out of 20 lesions were staged correctly by MRI
      using arthroscopy as a gold standard. Due to metal artifacts and morphological
      changes the postoperative MRI could not be used for staging. CONCLUSION: A
      preoperative MRI investigation is indicated in patients with ankle pain of
      unknown origin, a normal radiograph and a suspected osteochondral lesion of the
      talus. MRI is not indicated to determine the localization and the stage of an
      osteochondral lesion. A postoperative MRI is only necessary for the exclusion of
      a secondary pathology.

PMID- 15472776
TI  - [Chiropractic manipulation and spinal epidural hematoma--what came first?].

PMID- 15472775
TI  - [Calcaneal cyst: a classical simple bone cyst?].
AB  - INTRODUCTION: In the calcaneus differentiation between a solitary cyst and
      intraosseus lipoma is difficult. Radiologists frequently diagnose an intraosseus
      lipoma, whereas histology shows the classical signs of a solitary bone cyst. We
      present 12 cases of a solitary cyst of the calcaneus. MATERIAL AND METHODS:
      Between 1993 and 2001 we operated on 12 patients (8 men, 4 women, median age 28
      +/- 14 years) with calcaneal cysts. 9 patients received a curretage and an
      autologous, one patient a homologous, one patient a mixed autologous-homologous
      bone-grafting and one patient only a curretage (due to the small diameter of the
      cyst) of their cysts. RESULTS: No case revealed the histological picture of a
      fatty formation, which appears to be typical for an intraosseus lipoma. All of
      the microscopic findings resembled the characteristics seen in cysts of the long
      bones. A pathological fracture has not been observed. CONCLUSION: The
      histologically confirmed calcaneal cysts showed the radiological signs that are
      supposed to be typical for an intraosseous lipoma. It cannot be decided whether
      the histologically diagnosed calcaneal lipomas described by others can be
      interpreted as fatty degeneration of a calcaneal cyst, or whether fatty areas of
      the bone marrow have given a wrong impression. Since the literature only
      describes single isolated cases of a pathological fracture of the calcaneal cyst
      or lipoma, asymptomatic patients should be treated non-operatively.

PMID- 15472777
TI  - [Limited efficacy of cholinesterase inhibitors in Alzheimer's dementia].

PMID- 15472778
TI  - [Efficacy, efficiency and evidence -- studies on donepezil].

PMID- 15472779
TI  - [Doubtful evidence for the use of the cholinesterase inhibitor donepezil in
      patients with dementia--a systematic review].
AB  - OBJECTIVE: Objective of this systematic review is to determine the level of
      scientific evidence for the use of Donepezil in Alzheimer's Disease. METHODS: Ten
      randomised controlled double-blind trials testing Donepezil versus Placebo were
      identified in MEDLINE and EMBASE. All ten trials were included in this systematic
      review. Following a detailed catalogue of criteria the methodological standard of
      the ten trials was assessed. RESULTS: The authors of eight trials postulated
      statistically significant differences in favour of Donepezil. Unfortunately, the
      methodological standard of all studies was insufficient. The methodological
      shortcomings are discussed in detail. CONCLUSION: With regard to severe
      methodological deficiencies the evidence for the use of Donepezil in moderate to
      severe Alzheimer's Disease is lacking. But even if the trials had been conducted
      in a methodologically correct way the clinical relevance of the postulated
      positive results would have to be questioned.

PMID- 15472780
TI  - [Anxiety in elderly people -- epidemiology, diagnostic features and therapeutic
      options].
AB  - Anxiety disorders in older age represent with a prevalence rate of 10 % an
      important psychiatric problem, which has not been adequately recognised and
      diagnosed. This can be explained from the idea, that pathologic anxiety was
      evaluated as a normal reaction by elderly people. The actual classification of
      anxiety disorders with ICD-10 or DSM-IV was not sufficient and should be
      complemented by a syndromanal approach. The comorbidity of anxiety disorders with
      other psychiatric disorders, e. g. depression, and also with somatic diseases was
      high. The psychosocial consequences are important. Psychopharmacological and
      psychotherapeutic interventions have been proven in some studies and should be
      practised more in the future.

PMID- 15472781
TI  - [Psychological impact of the new digital media].
AB  - This review article starts from the hypothesis that the new digital media's
      impact on people's mental health, which in professional and private everyday life
      has become increasingly frequent and intense, is widely underestimated. The
      disturbances associated with media exposure, which have been already described
      and examined, are presented and discussed, while classifying them in three groups
      of disorders, namely dissocial, dissociative and impulse control disorders. In a
      second step, psychotherapeutic and psychiatric applications of the digital media
      are presented, especially, psychometric and neuropsychological testing,
      distribution of information and behavioral therapeutic tools. The positive and
      negative effects of the internet and cyberspace are applied to the multicausal
      understanding of the genesis and therapy of mental disturbances. Against this
      background, the opinion is held, that the paradigmatic medialization of the world
      has to be taken seriously and actively approached as a psycho-ecological factor
      with psychosocial, psychopathogenic and also neuroplastic effects. Therefore,
      also a psychiatric approach is needed to establish both research on media
      associated disorders including their therapy and the development of quality
      standards in the therapeutic use of the Internet and Cyberspace.

PMID- 15472783
TI  - [Trigemino-autonomous headaches].

PMID- 15472782
TI  - [Atomoxetine for the treatment of attention-deficit/hyperactivity disorder].
AB  - Atomoxetine is a selective noradrenaline reuptake inhibitor that has been studied
      for use in the treatment of attention-deficit/hyperactivity disorder (ADHD). In
      vitro, ex vivo and in vivo studies have shown that atomoxetine is a highly
      selective antagonist of the presynaptic norepinephrine transporter with little or
      no affinity for other noradrenergic receptors or other neurotransmitter
      transporters or receptors. So far, two open-label and seven randomised, double
      blind, placebo-controlled, clinical trials have been published, six in youths and
      three in adults. Each of these trials has shown a positive response as measured
      by the primary efficacy measures, the ADHD-IV Rating Scale (ADHD RS) or the
      Conners Adult ADHD Rating Scale (CAARS). Atomoxetine has generally been well
      tolerated. The most common treatment-related adverse event was decreased
      appetite. Atomoxetine shows no abuse potential and is not a controlled substance
      in the US. In November of 2002 the FDA approved atomoxetine for use in the US for
      the treatment of ADHD in children, adolescents and adults. Atomoxetine is the
      first nonstimulant approved by the FDA for the treatment of ADHD and the first
      medication approved for the treatment of adult ADHD.

PMID- 15472784
TI  - [Current developments in rehabilitation].

PMID- 15472785
TI  - [The "rehabilitation sciences" research funding programme: research findings --
      implementation -- impact and perspectives].
AB  - In 1998, the German Federal Ministry of Education and Research (BMBF) and the
      German pension insurance scheme established a funding programme for research in
      rehabilitation. This "Rehabilitation Sciences" research funding programme
      comprises eight regional research networks for eight years in two periods (1998
      2002, 2001-2005). In our paper we review the findings of the first funding period
      in five of the research fields: patient education, need for and access to
      rehabilitation, vocational training in medical rehabilitation to enhance return
      to work, comorbid mental disorders in patients with somatic diseases, and gender
      differences. Several activities aimed at transferring research findings into
      practice are outlined. Finally, the impact of the funding programme is summarized
      and perspectives for further funding are given.

PMID- 15472786
TI  - [Quality assurance in rehabilitation: where do we stand today?].
AB  - In the sector of medical rehabilitation in Germany, a quality assurance programme
      has been established over the last decade. What distinguishes this programme in
      comparison to other sectors of the health care system is its comprehensive
      approach (including quality of structures, processes and outcomes), the special
      attention given to patients' needs, its scientific foundation, and its
      implementation throughout the sector. Participation in this programme is
      obligatory for all in-patient rehabilitation facilities. For out-patient
      rehabilitation, a specific programme is currently being developed. The feedback
      report to the facilities gives them concrete indications of existing strengths
      and weaknesses and thus offers them a start for developing their quality by means
      of internal quality management. The article begins with a presentation of the
      instruments and procedures applied as well as selected results of the previous
      surveys in the context of external quality assurance. Subsequently, the most
      important approaches to internal quality management are explained. The article
      ends with a description of the strengths and weaknesses of the existing quality
      assurance programmes and proposes steps to be taken for their further
      development.

PMID- 15472787
TI  - [Chances for advancement of outpatient rehabilitation in Germany].
AB  - Rehabilitation has a long tradition in Germany compared to other countries and is
      based upon a differentiated, social law foundation. Rehabilitative offers are
      provided as standard benefits by different social insurance schemes (pension
      insurance, health insurance, accident insurance, etc.) and are an independent
      task of care not included in acute care. A high degree of institutionalisation
      and specialisation are specific characteristics of rehabilitation in Germany. A
      country-wide network of indication specific, mostly larger institutions is
      available for medical rehabilitation in Germany. This emergence of centres and
      the location of many institutions in more rural regions give rise to the fact
      that rehabilitation often cannot take place close to the places of residence of
      those who are in need of rehabilitative offers. Until the mid-nineties,
      rehabilitative benefits have been performed almost exclusively on an inpatient
      basis, which is another characteristic of medical rehabilitation in Germany.
      Since then the discussion about ambulant rehabilitation has been increasing.
      Several initiatives are aimed at supplementing the present in-patient offers
      through ambulant measures. This article describes and analyses the present
      efforts for the development of ambulant rehabilitation. In reference to the
      guidelines of the BAR (Federal Rehabilitation Council) concerning ambulant
      medical rehabilitation, adopted by all institutions involved in 2000, the current
      situation and the state of implementation are discussed, and advancements
      necessary in the authors' view are considered.

PMID- 15472788
TI  - [Geriatric rehabilitation in Germany: service provision policy and structural
      aspects from a statutory health insurance perspective].
AB  - The so-called shifting of paradigm in medicine has inevitably led to an
      increasing importance of medical rehabilitation, especially geriatric
      rehabilitation, within the system of medical care in the Federal Republic of
      Germany. Nationally valid guidelines for assessing the indication of geriatric
      rehabilitation and for recommending options for appropriate allocation have been
      elaborated within the framework of the German statutory health insurance system.
      In addition, manpower and equipment requirements for ambulatory geriatric
      rehabilitation facilities have been agreed on. These guidelines include
      clarifications concerning the following: definition of the geriatric patient;
      definition of the patient in need of geriatric rehabilitation; demarcation of
      geriatric rehabilitation from organ-specific rehabilitation; operationalization
      of assessment procedures and allocation recommendations concerning geriatric
      rehabilitation; requirements profiles for ambulatory geriatric rehabilitation
      facilities. Essential prerequisites for successful implementation of these
      national standards are among others: turning towards the bio-psycho-social model
      of health and disease advocated by the World Health Organization; overcoming the
      traditional deficit model of aging and old-age in favour of a resource-oriented
      approach in service-provision policies; rejecting the one-sided fiscal thinking
      in the current debate over service-provision policies in geriatric
      rehabilitation.

PMID- 15472789
TI  - [Practice guidelines in rehabilitation: infringement upon physicians' autonomy or
      foundation for better outcomes?].
AB  - Clinical practice guidelines - seen as an aggregation of scientific evidence -
      and evidence based medicine are of relevance and importance for everybody
      involved in health care. Nevertheless, the discussion of their pros and cons is
      controversial. Major criticisms concern methodological aspects, a disregard of
      the patients' perspective, potentially increasing costs and the limitation of
      doctors' autonomy possibly caused by streamlining therapy. Supporters emphasize
      the improvement of care that comes with using proven therapies, patients'
      empowerment, cost reduction and equity in the distribution of resources.
      Following medical practice guidelines the liability for medical malpractice may
      be limited, but non-adherence to guidelines does not entail liability per se.
      Clinical practice guidelines in the rehabilitative sector differ from those in
      curative medicine by being required to achieve more complex goals than
      maintenance, recovery and improvement of health. Activities in the rehabilitation
      sector address two main topics: The integration of rehabilitation into curative
      guidelines, e. g. by participating in the German clearing process for guidelines,
      and the development of guidelines specific to rehabilitation. There are a number
      of guideline initiatives, e. g. with the Association of the Scientific Medical
      Societies (AWMF), the Federation of German Pension Insurance Institutes (VDR) and
      the Federal Insurance Institute for Salaried Employees (BfA). The BfA project is
      the first to allow integration of evidence based medicine into the quality
      assurance programme of the German Pension Insurance complementing it with
      differentiated criteria for the assessment of therapeutic processes. Taking
      evidence based medicine increasingly into consideration and the continuous
      process of introducing rehabilitative clinical practice guidelines are going to
      improve health care for people with chronic diseases.

PMID- 15472790
TI  - [New forms of remuneration and care delivery: their impact on rehabilitation].
AB  - Current health policy reform efforts in Germany include introduction of a DRG
      (Diagnosis Related Group) based funding system in the hospital sector as well as
      integrated delivery of health care and disease management programs, developments
      that will directly affect the medical rehabilitation sector. Decreasing lengths
      of hospital stay induced by the DRG system will inter alia entail a shifting of
      cases and costs to subsequent sectors. Moreover, hospitals might not least seek
      compensation for shorter hospital stays by extending their scope to include
      rehabilitation and long-term care services. Introduction of the DRG system in
      acute-hospital care has resulted in major changes in respect of early
      rehabilitation. Existing specialized early rehabilitation facilities providing
      high-quality care face serious funding problems on account of the newly
      introduced early rehabilitation DRGs. For hospitals previously not involved in
      early rehabilitation on the other hand, incentives arise to set up new early
      rehabilitation structures although the need for these additional capacities
      obviously is questionable. Introduction of the DRG-based funding system has
      reinforced the discussion about applying a flat-rate system also in the
      rehabilitation sector. This form of remuneration however is inappropriate to
      medical rehabilitation concepts. On the other hand, a remuneration system
      incorporating cross-institutional per-diem fees and "treatment time" budgets
      might enable using essential advantages of flat-rate payment without having to
      expect repercussions for the quality of care. In the context of integrated care
      and disease management programs the issue at stake for rehabilitation primarily
      is to be able to contribute its specific competencies appropriately. Also,
      integrated health care is bound to result in stronger competition among the
      various health care sectors. If rehabilitation is set to face this competition,
      further research efforts will urgently have to be made along with ongoing
      development of clinical practice guidelines.

PMID- 15472791
TI  - [Services and benefits for medical rehabilitation and integrated health care].
AB  - Although created already under the Law on statutory health insurance reform 2000,
      implementation and actual practice of the instrument of "integrated health care"
      (section 140 a-g of the German Social Code, Book V) have noticeably been gaining
      momentum only since the Law on statutory health insurance modernization (GMG)
      came into force on January 1, 2004. In this process, the issue of coping with the
      interface between medical acute care and medical rehabilitation emerges as an
      increasing focus of the debate over future-oriented development of service
      provision structures. When Book IX of the German Social Code -- Rehabilitation
      and Participation of People with Disabilities -- came into force on July 1, 2001
      its stipulations became binding also for the Statutory Health Insurance domain
      (Book V of the German Social Code), notably in as far as regulations of
      healthcare infrastructure, contents of benefits and services as well as their
      performance are concerned. Moreover, more than 75 % of the medical rehabilitation
      benefits granted are performed by rehabilitation providers outside the scope of
      the health insurance system. This contribution points out that the development of
      integrated care structures which also cover medical rehabilitation benefits and
      services is subject to interdisciplinary and multidisciplinary requirements that,
      partly to a considerable extent, differ from or go beyond the framework
      conditions usually applicable in the acute-care sector.

PMID- 15472792
TI  - The efficacy and safety of probiotic Lactobacillus rhamnosus GG on prolonged,
      noninfectious diarrhea in HIV Patients on antiretroviral therapy: a randomized,
      placebo-controlled, crossover study.
AB  - PURPOSE: The aim of this placebo-controlled, crossover study was to evaluate the
      efficacy and safety of probiotic Lactobacillus rhamnosus GG (LGG) in ameliorating
      gastrointestinal symptoms in HIV-infected patients on antiretroviral therapy.
      METHOD: Infectious causes for diarrhea (bacteria, ova, parasites, and viruses
      including cryptosporidium, microsporidia, and cyclospora) were excluded with
      fecal samples before the study. HIV-infected patients with diarrhea for more than
      1 month received in randomized order probiotic LGG preparation (containing viable
      LGG 1-5 x 1010 cfu/dose) and placebo twice a day for 2 weeks. Gastrointestinal
      symptoms were assessed daily and included the daily number of bowel movements,
      classification of stool consistency (watery, semi-watery, loose, firm, or
      foaming), and Visual Analog Scale (VAS) of gastrointestinal symptoms (flatulence,
      stomach pain, bloating disorders, general well-being). RESULTS: Seventeen HIV
      infected patients completed the study. There were no significant differences
      between the treatment groups in the frequency or the consistency of diarrhea. In
      the VAS assessments of gastrointestinal symptoms, no difference between LGG and
      placebo could be detected. No adverse events were reported. The number of HIV RNA
      copies in the blood and CD4 cell counts remained stable during the study.
      CONCLUSION: Probiotic LGG preparation was well-tolerated in HIV infected
      patients. No significant differences in noninfectious diarrhea or
      gastrointestinal symptoms compared to placebo could be observed in this crossover
      study.

PMID- 15472794
TI  - Predictors of virological response to atazanavir in protease inhibitor
      experienced patients.
AB  - BACKGROUND: Atazanavir (ATV) is the latest approved HIV protease inhibitor (PI).
      Even though it is very convenient (only two capsules once a day), concerns have
      risen about its potency. METHOD: The clinical performance of ATV 400 mg once a
      day was examined in all PI-experienced patients who were included in the ATV
      expanded access program conducted in a single institution. The predictive value
      of baseline drug resistance HIV genotypes, ATV plasma trough levels, and the
      genotypic inhibitory quotient (GIQ) on the virological response at week 24 was
      assessed. RESULTS: Data from 92 patients were analyzed. ATV was prescribed as
      part of a rescue intervention (45%), a simplification strategy (11%), or an
      attempt to ameliorate hyperlipidemias (23%) or other toxicities (16%). Tenofovir
      (TDF) was concomitantly used with ATV in 78% of patients. None received ritonavir
      boosting. In patients with detectable viremia at baseline (65%), the median HIV
      RNA drop was 0.7 logs. The median ATV Cmin was 0.12 microg/mL (IQR, 0.05-0.22
      microg/mL), which is clearly above the IC90 (90% inhibitory concentration) for
      ATV in wild-type viruses. The virological response did not correlate
      significantly with ATV Cmin. The median number of protease resistance mutations
      was lower in patients showing virological response than in nonresponders (1 vs.
      5; p=.07). A higher HIV RNA drop was associated with a higher GIQ (p=.02; beta=
      5.4; 95% CI, -10 to -1). Only 4 patients (4%) discontinued treatment due to ATV
      related toxicities (hyperbilirubinemia in 1). Bilirubin levels were associated
      with ATV plasma concentrations (p=.05; beta=3.2; 95% CI, -0.1 to 6.5). The rate
      of hypertriglyceridemia and hypercholesterolemia declined significantly with
      respect to baseline. CONCLUSION: ATV is relatively safe and provides significant
      virological response in PI-experienced patients, mainly among those with a low
      number of protease resistance mutations. The GIQ predicts accurately the
      virological response in patients receiving ATV. Hyperbilirubinemia is associated
      with higher ATV plasma levels.

PMID- 15472793
TI  - Progression of lipodystrophy (LD) with continued thymidine analogue usage: long
      term follow-up from a randomized clinical trial (the PIILR study).
AB  - PURPOSE: During the 24-week PIILR study of protease inhibitor (PI) withdrawal,
      improved lipids and reduction in intraabdominal visceral fat was seen, however,
      there was also a loss of subcutaneous limb fat in patients with HIV-lipodystrophy
      (LD). It was hypothesized that overall improvement in LD may require a longer
      period of time off PIs. METHOD: Follow-up of patients randomized to stop or
      continue PI-based therapy for 24 weeks, in a multicenter study, was continued for
      up to 120 weeks. Biochemistry and lipid parameters were assessed every 3 months.
      DEXA and CT scans were performed annually. Limb fat, visceral adipose tissue, and
      the lipodystrophy case definition score (LCDS) were used as indicators of LD
      severity. RESULTS: Forty-five male patients with baseline and week 120 body
      composition data were assessed. There were no significant changes in the limb fat
      or visceral adipose tissue (VAT) components of LD, with the exception of the LCDS
      (change from baseline +5.79, p < .001). Control of viral replication was
      maintained and lipid and glycemic parameters were unchanged over the 120-week
      follow-up. Linear regression analysis showed on-study usage of stavudine was
      independently and significantly correlated with both decreased limb fat mass and
      a higher LCDS. CONCLUSION: Body composition or metabolic features of LD did not
      improve over 2 years of observation in patients remaining on predominantly PI
      sparing therapy. LD was adversely influenced by continued stavudine use.

PMID- 15472795
TI  - A decade surveillance study of Mycobacterium xenopi disease and antimicrobial
      susceptibility levels in a reference teaching hospital of northern Italy: HIV
      associated versus non-HIV-associated infection.
AB  - OBJECTIVE AND METHOD: The aim of our survey is to investigate the epidemiology
      and in vitro antimicrobial susceptibility levels of 35 consecutive Mycobacterium
      xenopi strains responsible for confirmed disease at a University Hospital from
      1993 to 2002 and to identify eventual differences in the in vitro sensitivity
      profile between the 17 strains isolated from patients with HIV disease and the 18
      isolates cultured from non-HIV-infected individuals. RESULTS: The involvement of
      lower airways accounted for 88.6% of cases; but atypical pulmonary findings,
      including cavitation and a prominent inflammatory reaction, recently emerged in
      HIV-infected patients successfully treated with HAART, which raises the possible
      role of immune reconstitution syndrome in the clinical pathomorphism of this
      opportunistic disease. When compared with non-HIV-infected patients, patients
      with HIV disease had a lower mean age and a tendency to suffer from late
      relapses. The greatest overall in vitro sensitivity rate was registered for
      capreomycin and protionamide (100% of strains) followed by kanamicin (96.6%),
      whereas susceptibility rates for the first-line compounds such as ethambutol,
      isoniazid, and rifampicin were slightly lower (85.7% to 91.4%). No temporal
      variation in the susceptibility index was seen over the study decade. Non-HIV
      infected patients experienced a higher frequency of M. xenopi isolates that
      proved to be resistant to at least one tested compound compared with HIV
      associated episodes, despite the heavy and prolonged exposure of HIV-infected
      patients to broad spectrum antimicrobials, which included agents effective on
      atypical mycobacteria. Only one HIV-positive patient developed rifampicin
      resistance in his third disease recurrence. CONCLUSION: A rapid diagnosis, a
      reliable differentiation between colonization and disease, and an optimal
      therapeutic choice for atypical mycobacterial disease (including M. xenopi one)
      are still serious challenges for clinicians and bacteriologists who treat
      immunocompromised patients, such as those with HIV disease. In the
      immunocompromised host, diagnostic difficulties posed by late identification and
      eventually concurrent opportunistic disorders add their negative effects to
      therapeutic problems due to the unpredictable in vitro susceptibility profile of
      atypical mycobacteria, such as M. xenopi.

PMID- 15472796
TI  - Usefulness of therapeutic drug monitoring of antiretrovirals in routine clinical
      practice.
AB  - BACKGROUND: Clinical trials have shown that therapeutic drug monitoring (TDM) of
      antiretrovirals (ARV) improves patient care. However, little is known about the
      usefulness of TDM in routine practice. METHOD: We reviewed all the trough
      concentrations of protease inhibitors and nonnucleoside reverse transcriptase
      inhibitors that were performed for therapeutic failure, suspected drug toxicity,
      or routine purposes. RESULTS: Between 1998 and 2001, 146 TDMs were done in 109
      HIV patients. Of the 48 patients with therapeutic failure, 62% had resistance to
      ARV with adequate ARV concentrations, 16% had insufficient drug exposure without
      any ARV resistance mutations, and 16% combined both resistance and suboptimal
      drug concentrations. Subsequent therapeutic interventions (increasing adherence
      and/or changing HAART) resulted in an undetectable viral load in 37.5% of the
      patients (14/48). Five (24%) of 21 patients with suspected drug toxicity had high
      drug concentrations associated with side effects. In all the cases, adverse
      events regressed after reduction of drug dosage. Of the 77 TDMs done for routine
      purposes, 26% were outside the therapeutic range. CONCLUSION: The data show that
      TDM of ARVs in the clinical setting provides important information that can be
      used to improve the management of HIV patients receiving antiretroviral therapy.

PMID- 15472798
TI  - New hopes for HIV and HCV coinfection in 2004.
AB  - An increase in liver-related causes of death in HIV-positive patients who are
      coinfected with the hepatitis C virus (HCV) has been acknowledged over the last
      few years, particularly since the mid 1990s, when the natural history of HIV
      infection started to improve with the use of highly active antiretroviral therapy
      (HAART). Chronic hepatitis C is very common among HIV-infected patients who were
      infected through intravenous drugs use or contaminated blood products (e.g.,
      hemophiliacs). The bidirectional interferences between HIV and HCV modify the
      natural history of both infections. Moreover, interactions between anti-HIV and
      anti-HCV drugs are of concern, and a lower response to anti-HCV therapy limits
      its benefit in HIV-coinfected patients. Although a slower HCV RNA decay is seen
      in coinfected patients after standard therapy is initiated with pegylated
      interferon plus ribavirin, the stopping rule at week 12 that is recommended for
      HCV-monoinfected individuals seems to be equally valid in HIV-positive patients.
      This finding is of great value, because it allows treatment to be offered in the
      absence of contraindication (e.g., low CD4 count, alcohol abuse, etc.) but
      discontinued as early as 12 weeks when no chances of cure are predicted, which
      saves costs and deleterious side effects. HAART therapy seems to temper somehow
      the negative impact exerted by HIV infection over HCV-related liver fibrosis.
      Liver transplantation is currently the best option for HIV-infected patients with
      end-stage liver disease. However, the management of patients on the waiting list
      and after transplantation carries significant new challenges. New anti-HCV drugs
      are urgently needed and new strategies with the currently available drugs need to
      be assessed to reduce the negative impact of hepatitis C in HIV-coinfected
      individuals.

PMID- 15472797
TI  - An example of nonrandom missing data for hepatitis C virus status in a prognostic
      study among HIV-infected patients.
AB  - PURPOSE: To describe information bias due to missing data for hepatitis C (HCV)
      status in the analysis of factors associated with mortality in HIV-infected
      patients. METHOD: The prospective APROCO cohort enrolled 1,151 HIV-infected
      adults at the first initiation of highly active antiretroviral treatment in 1997
      1998. Conversely to other characteristics, hepatitis B and C serologic status
      were recorded retrospectively. RESULTS: In a first dataset, HCV status was
      missing in 29%. HCV infection was associated with a higher hazard of death (Cox
      model, hazard ratio [HR]=4.1; 95% confidence interval [95% CI], 1.5-11.3). After
      more efforts to actively document HCV status, the information remained missing in
      only 10%. All deceased patients who were secondarily documented were recorded as
      being HCV negative. In fact, before systematic collection of HCV status,
      nonstructured additional documentation for all deaths led to spontaneous
      notification of HCV-positive serology at death and not HCV negative. HCV was no
      longer associated with the hazard of death (HR=1.2; 95% CI, 0.6-2.7). CONCLUSION:
      These results underline the need to minimize missing data and to investigate the
      impact of missing data on the results, although the mechanism of bias is
      difficult to identify. In addition, these results might shed light on the current
      debate about the association between HCV and progression of HIV infection.

PMID- 15472799
TI  - HIV drug adverse events: selected highlights from the 15th International AIDS
      Conference.

PMID- 15472800
TI  - The oral AIDS vaccine,V-1 Immunitor.

PMID- 15472801
TI  - Voriconazole-induced QT interval prolongation and ventricular tachycardia: a non
      concentration-dependent adverse effect.
AB  - A 15-year-old patient with acute lymphoblastic leukemia and Fusarium infection
      was treated with voriconazole. She developed asymptomatic bradycardia, QT
      interval prolongation, and nonsustained, polymorphic ventricular tachycardia,
      which recurred upon rechallenge with the drug. Voriconazole levels and metabolism
      were within expected normal values. This non-concentration-dependent,
      voriconazole-associated ventricular tachycardia mandates cardiac rhythm
      monitoring during voriconazole treatment.

PMID- 15472802
TI  - Prolonged survival of an HIV-infected patient with multidrug-resistant
      Mycobacterium bovis infection treated with surgical resection.
AB  - We describe a case of multidrug-resistant tuberculosis due to Mycobacterium bovis
      in a human immunodeficiency virus-infected woman with good immunologic status.
      The patient presented with a hard mass measuring 10 cm in diameter on the lower
      left ribs and a lung nodule measuring 3 cm in diameter in the left superior lobe.
      No adequate pharmacological treatment was available. Both lesions were surgically
      resected. The patient has remained asymptomatic (without fever, cough,
      lymphadenopathy, or cutaneous masses) for 20 months, after discharge from the
      hospital.

PMID- 15472803
TI  - Transmission of dengue virus without a mosquito vector: nosocomial mucocutaneous
      transmission and other routes of transmission.
AB  - We report a case of dengue fever in a Boston-area health care worker with no
      recent history of travel but with mucocutaneous exposure to infected blood from a
      febrile traveler who had recently returned from Peru. Serologic tests confirmed
      acute dengue virus infection in both the traveler and the health care worker. We
      believe that this is the first documented case of dengue virus transmission via
      the mucocutaneous route. We present case reports and review other ways that
      dengue virus has been transmitted without a mosquito vector.

PMID- 15472804
TI  - Safety and pharmacokinetic evaluation of intravenous vaccinia immune globulin in
      healthy volunteers.
AB  - BACKGROUND: Vaccinia immune globulin (VIG) administered via the intramuscular
      route has historically been used for the treatment of complications of smallpox
      vaccination. Intravenous formulations of VIG are required to improve tolerability
      and pharmacokinetic profile. METHODS: We conducted 2 separate studies to evaluate
      the feasibility of administration of an intravenous formulation of antivaccinia
      immune globulin (VIGIV). The first study assessed the pharmacokinetics and safety
      of a newly manufactured lyophilized VIG product for intravenous administration
      (VIGIV-lyo). Seventy-eight healthy volunteers received an intravenous infusion of
      VIGIV-lyo at doses of 100 mg/kg, 200 mg/kg, or 500 mg/kg. In the second study, we
      evaluated the safety of a liquid product of VIGIV (VIGIV-liq) in 33 healthy
      volunteers receiving an intravenous infusion of 100 mg/kg VIGIV-liq. RESULTS: The
      geometric mean titer of VIG at the target dose (100 mg/kg) after intravenous
      administration is 2.5 times higher than the predicted geometric mean titer after
      intramuscular injection (P<.001). The pharmacokinetics of VIGIV-lyo are linear
      for doses from 100 mg/kg through 500 mg/kg. Administration of the 200-mg/kg and
      500-mg/kg doses of VIGIV-lyo does not result in markedly higher adverse event
      rates. The adverse event rates observed with the liquid product are comparable to
      those seen with the lyophilized product. CONCLUSIONS: These 2 studies suggest
      that intravenous administration of VIG is well tolerated and results in a more
      favorable pharmacokinetic profile than does VIG administered intramuscularly.

PMID- 15472805
TI  - Henry Kempe and the birth of vaccinia immune globulin.

PMID- 15472806
TI  - A randomized, double-blind trial of anidulafungin versus fluconazole for the
      treatment of esophageal candidiasis.
AB  - Anidulafungin is a novel antifungal agent of the echinocandin class. This
      randomized, double-blind, double-dummy study compared the efficacy and safety of
      intravenous anidulafungin to that of oral fluconazole in 601 patients with
      endoscopically and microbiologically documented esophageal candidiasis. Patients
      received intravenous anidulafungin (100 mg on day 1, followed by 50 mg per day)
      or oral fluconazole (200 mg on day 1, followed by 100 mg per day) for 7 days
      beyond resolution of symptoms (range, 14-21 days). At the end of therapy, the
      rate of endoscopic success for anidulafungin (242 [97.2%] of 249 treated
      patients) was found to be statistically noninferior to that for fluconazole (252
      [98.8%] of 255 treated patients; treatment difference, -1.6%; 95% confidence
      interval, -4.1 to 0.8). The safety profile of anidulafungin was similar to that
      of fluconazole; treatment-related adverse events occurred in 9.3% and 12.0% of
      patients, respectively. Laboratory parameters were similar between treatment
      arms. Anidulafungin is as safe and effective as oral fluconazole for the
      treatment of esophageal candidiasis, when assessed at the completion of therapy.

PMID- 15472807
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) nares colonization at hospital
      admission and its effect on subsequent MRSA infection.
AB  - BACKGROUND: Asymptomatic colonization with methicillin-resistant Staphylococcus
      aureus (MRSA) has been described as a risk factor for subsequent MRSA infection.
      MRSA is an important nosocomial pathogen but has currently been reported in
      patients without typical risk factors for nosocomial acquisition. This study was
      designed to evaluate the impact of asymptomatic nares MRSA colonization on the
      development of subsequent MRSA infection. The incidence of MRSA infection was
      examined in patients with and patients without MRSA or methicillin-susceptible S.
      aureus (MSSA) colonization at admission to the hospital and in those who
      developed colonization during hospitalization. METHODS: Patients admitted to 5
      representative hospital units were prospectively evaluated. Nares samples were
      obtained for culture at admission and during hospitalization. Laboratory culture
      results were monitored to identify all MRSA infections that occurred during the
      study period and 1 year thereafter. RESULTS: Of the 758 patients who had cultures
      of nares samples performed at admission, 3.4% were colonized with MRSA, and 21%
      were colonized with MSSA. A total of 19% of patients with MRSA colonization at
      admission and 25% who acquired MRSA colonization during hospitalization developed
      infection with MRSA, compared with 1.5% and 2.0% of patients colonized with MSSA
      (P<.01) and uncolonized (P<.01), respectively, at admission. MRSA colonization at
      admission increased the risk of subsequent MRSA infection, compared with MSSA
      colonization (relative risk [RR], 13; 95% confidence interval [CI], 2.7-64) or no
      staphylococcal colonization (RR, 9.5; 95% CI, 3.6-25) at admission. Acquisition
      of MRSA colonization also increased the risk for subsequent MRSA infection,
      compared with no acquisition (RR, 12; 95% CI, 4.0-38). CONCLUSION: MRSA
      colonization of nares, either present at admission to the hospital or acquired
      during hospitalization, increases the risk for MRSA infection. Identifying MRSA
      colonization at admission could target a high-risk population that may benefit
      from interventions to decrease the risk for subsequent MRSA infection.

PMID- 15472808
TI  - Utility of fast mycobacterial interspersed repetitive unit-variable number tandem
      repeat genotyping in clinical mycobacteriological analysis.
AB  - BACKGROUND: Analysis of variable numbers of tandem repeats (VNTR) of genetic
      elements called mycobacterial interspersed repetitive units (MIRUs) is a recently
      described, polymerase chain reaction (PCR)-based method used to genotype
      Mycobacterium tuberculosis. It is much faster, requires a smaller amount of DNA,
      and has approximately the same discriminatory power as the standard IS6110
      restriction fragment-length polymorphism (RFLP) method. We report the adaptation
      and optimization of MIRU-VNTR genotyping on a capillary electrophoresis system.
      We describe its application to 3 typical clinical situations encountered in our
      laboratory (Institut Pasteur de Bruxelles, Laboratoire Tuberculose et
      Mycobacteries; Brussels, Belgium). METHODS: MIRU-VNTR genotyping was performed on
      heat-inactivated M. tuberculosis cultures obtained from clinical specimens on
      Lowenstein solid medium or in mycobacteria growth indicator liquid tubes (Becton
      Dickinson). After amplification of 12 genomic loci using 4 different multiplex
      PCRs, DNA fragments were separated by capillary electrophoresis using the ABI
      Prism 3100-Avant Genetic Analyzer (Applied Biosystems). Sizing of the PCR
      fragments and assignment of the various MIRU-VNTR alleles were done using the
      GeneScan and customized Genotyper software packages (PE Applied Biosystem).
      RESULTS: Clustering on the basis of IS6110 fingerprinting of isolates from 3
      different patients attending the same hospital was confirmed by MIRU-VNTR typing.
      This concordance between 2 independent, highly discriminatory techniques was
      decisive in triggering an epidemiological inquiry that led to identification of a
      bronchoscopy-related tuberculosis nosocomial infection. A mixed tuberculosis
      infection in a patient whose infection was initially suspected as a result of the
      IS6110 RFLP method was clearly identified by MIRU-VNTR typing. Finally, automated
      MIRU-VNTR analysis permitted the identification of laboratory contamination in 6
      liquid cultures of M. tuberculosis within several hours. CONCLUSION: These
      examples illustrate the utility of this genotyping technique for quick and
      accurate resolution of problems commonly encountered in clinical
      mycobacteriology.

PMID- 15472809
TI  - Strong association of hepatitis C virus (HCV) infection and thrombocytopenia:
      implications from a survey of a community with hyperendemic HCV infection.
AB  - BACKGROUND: The role of hepatitis C virus (HCV) infection in thrombocytopenia
      (defined as a platelet count of <100,000 platelets/ mu L) is unknown. Our aim was
      to study the association between HCV infection and thrombocytopenia in a
      community where hepatitis B virus (HBV) and HCV infections are hyperendemic.
      METHODS: A community-wide survey of subjects > or =40 years old who had undergone
      a preventive health examination between April 1997 and July 2000 in A-Lein
      Township, Kaohsiung County, Taiwan. Serum blood platelet counts and HBV surface
      antigen (HBsAg) and antibody to HCV (anti-HCV) levels were measured. Abdominal
      sonography was performed on viral hepatitis-positive participants. RESULTS: Among
      the 1690 subjects, 70% were seronegative, 17.4% were anti-HCV positive, 9.2% were
      HBsAg positive, and 3.4% were coinfected with HCV and HBV. The mean platelet
      count in subjects with anti-HCV (180,000 platelets/microL) was lower than in
      those with HBsAg (201,000 platelets/microL) and in those without anti-HCV and
      HBsAg (234,000 platelets/microL) (P<.001). The prevalence of thrombocytopenia was
      1.3% among seronegative subjects, 1.9% among HBsAg-positive subjects, 5.2% among
      coinfected subjects, and 10.2% among anti-HCV-positive subjects. Multiple
      logistic regression analysis revealed that anti-HCV positivity (odds ratio, 6.0;
      95% confidence interval, 3.2-11.2), an alanine aminotransferase level of > or =40
      U/L, and age of > or =65 years were significantly associated with
      thrombocytopenia. The prevalence of thrombocytopenia among anti-HCV-positive
      subjects increased as the severity of liver disease increased, but, in HBsAg
      positive subjects, thrombocytopenia presented only in those with advanced liver
      disease. CONCLUSIONS: HCV infection is strongly associated with thrombocytopenia,
      which is correlated with hepatocellular damage and hepatic fibrosis. It is
      advisable to further check the hepatic condition of the patient, especially for
      HCV infection, if thrombocytopenia is present.

PMID- 15472810
TI  - Combination antifungal therapy for invasive aspergillosis.
AB  - BACKGROUND: Aspergillosis therapy with amphotericin, azoles, or echinocandins is
      associated with substantial mortality, ranging from 30% to 80%, depending on the
      stage of infection and the host's underlying disease. The results of in vitro
      studies and animal models suggest that combination therapy with azoles and
      echinocandins may have additive activity against Aspergillus species. METHODS: We
      evaluated the outcomes of patients with aspergillosis who experienced failure of
      initial therapy with amphotericin B formulations and received either voriconazole
      (n=31) or a combination of voriconazole and caspofungin (n=16) for salvage
      therapy. RESULTS: The combination of voriconazole and caspofungin was associated
      with improved 3-month survival rate, compared with voriconazole alone (hazard
      ratio [HR], 0.42; 95% confidence interval [CI], 0.17-1.1; P=.048). In
      multivariable models, salvage therapy with the combination of voriconazole and
      caspofungin was associated with reduced mortality, compared with therapy with
      voriconazole (HR, 0.28; 95% CI, 0.28-0.92; P=.011), independent of other
      prognostic variables (e.g., receipt of transplant and type of conditioning
      therapy). The probability of death due to aspergillosis was lowest in patients
      who received the combination regimen. CONCLUSIONS: Randomized trials are
      warranted to determine whether this combination should be used as primary therapy
      for aspergillosis.

PMID- 15472811
TI  - Combination therapy for invasive aspergillosis.

PMID- 15472812
TI  - Predicting the Staphylococcus aureus nasal carrier state: derivation and
      validation of a "culture rule".
AB  - BACKGROUND: To study determinants and risks of Staphylococcus aureus nasal
      carriage, adequate differentiation between the different S. aureus carrier states
      is obligatory. We set out to develop a "culture rule" capable of differentiating
      between persistent and intermittent or noncarriers that uses a minimum of nasal
      swab cultures. METHODS: In 51 healthy volunteers (derivation cohort), 12
      quantitative nasal cultures were performed to establish S. aureus nasal carriage
      states. Persons with 11 or 12 cultures positive for S. aureus were classified as
      persistent carriers, and those with negative results of all cultures were
      classified as noncarriers. All other persons were classified as intermittent
      carriers. By means of logistic regression and receiver operating characteristic
      (ROC) curves, a culture rule was derived. This culture rule was subsequently
      validated in 106 participants of an ongoing study in 3882 elderly persons, again
      with the use of 12 quantitative nasal cultures. RESULTS: In both cohorts, the
      positive predictive value of 2 consecutive positive culture results for
      persistent carriage was 79%. The model best differentiating between persistent
      and intermittent or noncarriers used the number of positive culture results
      combined with the amount of S. aureus in these cultures. By using the outcome of
      2 cultures, the areas under the ROC curves were 0.981 (95% confidence interval
      [CI], 0.949-1.0) for the derivation cohort and 0.936 (95% CI, 0.881-0.990) for
      the validation cohort. CONCLUSIONS: Combining qualitative and quantitative
      results of 2 nasal swab cultures accurately predicted the persistent S. aureus
      carriage state with a reliability of 93.6%. Thus, this culture rule can be used
      in studies of determinants and risks of S. aureus nasal carriage.

PMID- 15472813
TI  - Bloodstream infections caused by Enterobacter species: predictors of 30-day
      mortality rate and impact of broad-spectrum cephalosporin resistance on outcome.
AB  - BACKGROUND: Enterobacter species have become increasingly important nosocomial
      pathogens. However, resistance to cephalosporins often complicates the treatment
      of Enterobacter infection. This study was conducted to evaluate the predictors of
      mortality and the impact of cephalosporin resistance on outcome in patients with
      Enterobacter bacteremia. METHODS: A total of 183 patients with Enterobacter
      bacteremia were retrospectively analyzed. Broad-spectrum cephalosporin resistance
      was defined as in vitro resistance to cefotaxime or ceftazidime. The main outcome
      measure was the 30-day mortality rate. RESULTS: Of 183 patients, 86 (47%) had
      bacteremia caused by broad-spectrum cephalosporin-resistant Enterobacter species,
      and their infections were classified as resistant. The 30-day mortality rate of
      patients with resistant infections (the resistant group) was significantly higher
      than that of patients with susceptible infections (the susceptible group) (33.7%
      vs. 18.6%; P=.021). When the 30-day mortality rates were compared according to
      the primary sites of infection and underlying conditions, the 30-day mortality
      rates of the resistant group were significantly higher than those of the
      susceptible group, in patients with an unknown primary site of infection, or in
      patients with septic shock. Multivariate analysis showed that broad-spectrum
      cephalosporin resistance was one of the independent risk factors associated with
      30-day mortality (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.01
      13.52; P=.049). Presentation with septic shock and an increasing Acute Physiology
      and Chronic Health Evaluation II score were also independent risk factors for
      mortality (OR, 59.91 [95% CI, 14.93-240.15; P<.001] and 1.52 [95% CI, 1.24-1.86;
      P<.001], respectively). CONCLUSIONS: Broad-spectrum cephalosporin resistance
      adversely affects the outcome of patients with Enterobacter bacteremia,
      especially those with an unknown primary site of infection and those with septic
      shock.

PMID- 15472814
TI  - Clinical efficacy of intramuscular vaccinia immune globulin: a literature review.
AB  - BACKGROUND: Numerous literature reports describe clinical efficacy of
      intramuscular vaccinia immune globulin (VIG) for complications of smallpox
      vaccination, prophylaxis of individuals with contraindications to vaccination,
      and prevention of smallpox among close contacts of patients with smallpox.
      METHODS: We reviewed the literature regarding VIG treatment and prophylaxis of
      smallpox vaccine complications and the use of VIG as a preventative measure for
      close contacts of patients with smallpox. RESULTS: Data regarding intramuscular
      administration of VIG for treatment of smallpox vaccine complications occurred in
      16 articles, none of which reported formal controlled trials. The indications for
      treatment include generalized vaccinia, progressive vaccinia, eczema vaccinatum,
      and certain accidental implantations. Six publications suggest VIG efficacy for
      prophylaxis of vaccinial superinfection of eczema, burns, chickenpox,
      immunosuppression, pregnancy, or certain skin conditions. Prophylactic VIG has
      also been used in healthy military recruits to reduce the incidence of
      postvaccinial encephalitis. The use of intramuscular administration of VIG to
      prevent smallpox in contacts of patients with documented cases of smallpox is
      reported in 4 studies that compare contacts who received intramuscular
      administration of VIG with those who did not and in 1 observational study, with
      varying but promising results. CONCLUSIONS: Although controlled clinical trials
      do not exist to support the use of VIG for treatment of vaccinia-related
      complications or prophylaxis among individuals with contraindications to smallpox
      vaccination, available data suggest that VIG reduces morbidity and mortality
      associated with progressive vaccinia (vaccinia necrosum) and eczema vaccinatum.
      Furthermore, VIG seems to prevent vaccinial superinfection in patients with
      inflammatory skin diseases or burns, given the low incidence of vaccina-related
      complications associated with these conditions.

PMID- 15472815
TI  - When microbe meets human.
AB  - Microbes make up a significant component of the human body, yet relatively little
      is known about how they influence health and disease. They colonize after birth
      by chance and circumstance, yet play a major role in immunity, digestion, and
      protection against disease. In relatively recent times, basic science and
      clinical studies have clearly shown the potential impact of indigenous and
      exogenous microbes on human health and well-being. Yet regulatory bodies,
      research funding agencies, and health care practitioners, perhaps disillusioned
      by too many unreliable, overhyped products that are marketed under the guise of
      probiotics or natural therapeutics, have lagged far behind in embracing this
      avenue of enquiry. As more scientifically proven probiotic products differentiate
      themselves from untested and unproven cure-alls, and as multidisciplinary
      research groups piece together the diverse components of the puzzle, humans will
      slowly begin to understand how best to optimize their coexistence with microbial
      organisms, thus perhaps prolonging and enhancing life.

PMID- 15472816
TI  - Infectious disease screening for refugees resettled in the United States.
AB  - Refugees resettling in the United States carry a significant burden of infectious
      diseases as a result of exposures in their countries of origin and the
      circumstances of their migration. Overseas screening is required before entry,
      but it incompletely assesses infectious diseases in refugees. Domestic health
      assessment has the potential to provide more comprehensive assessment for
      infectious diseases. Screening protocols ideally should test for tuberculosis,
      hepatitis B, and intestinal and other parasites and should include mechanisms for
      providing or updating immunizations. Testing for other infectious diseases,
      including malaria, hepatitis C, human immunodeficiency virus, and sexually
      transmitted diseases, can be performed on the basis of clinical signs and
      symptoms. This article reviews the current status of overseas and domestic health
      screening for refugees, infectious disease burdens, and future goals for health
      assessment of refugees and other immigrants.

PMID- 15472817
TI  - A randomized, double-blind, parallel-group, dose-response study of micafungin
      compared with fluconazole for the treatment of esophageal candidiasis in HIV
      positive patients.
AB  - BACKGROUND: Severely immunocompromised individuals are highly susceptible to
      Candida infection of the esophagus. This randomized, double-blind study assessed
      the dose-response relationship of the new echinocandin antifungal, micafungin,
      compared with that of standard fluconazole treatment. METHODS: A total of 245
      patients (age, > or =18 years) with a prior diagnosis of acquired
      immunodeficiency syndrome/human immunodeficiency virus (HIV) infection and
      esophageal candidiasis, confirmed by endoscopy and culture, were randomized to
      receive micafungin (50, 100, or 150 mg per day) or fluconazole (200 mg per day).
      Both agents were administered once per day by a 1-h intravenous infusion for 14
      21 days. The primary efficacy end point was endoscopic cure rate, defined as
      endoscopy grade of 0 at the end of therapy. RESULTS: The endoscopic cure rate
      (grade 0) was dose-dependent with 50, 100, and 150 mg of micafungin per day at
      68.8%, 77.4%, and 89.8%, respectively. Symptoms improved or resolved rapidly (3-7
      days of treatment in the majority of patients). The endoscopic cure rate for 100
      and 150 mg of micafungin per day (83.5%) was comparable to that for 200 mg of
      fluconazole per day (86.7%; 95% confidence interval for the difference in
      endoscopic cure rate, -14.0% to 7.7%). The overall safety and tolerability was
      acceptable, with no important differences between micafungin (all doses) and
      fluconazole. CONCLUSIONS: The dose-response findings demonstrate a greater
      efficacy with micafungin at 100 and 150 mg per day than at 50 mg per day. This
      study also indicates that the efficacy of micafungin (at dosages of 100 and 150
      mg per day) was comparable to that of fluconazole, suggesting that micafungin
      represents a valuable new treatment option for esophageal candidiasis in HIV
      positive patients.

PMID- 15472818
TI  - Echinocandins: ask not what they can do for esophageal candidiasis--ask what
      studies of esophageal candidiasis can do for them.

PMID- 15472819
TI  - Delayed progression to death and to AIDS in a Hong Kong cohort of patients with
      advanced HIV type 1 disease during the era of highly active antiretroviral
      therapy.
AB  - BACKGROUND: The magnitude of the impact of highly active antiretroviral therapy
      (HAART) since its introduction in non-Western countries is not entirely clear. We
      studied disease progression among adult patients with advanced human
      immunodeficiency virus type 1 (HIV-1) infection in the pre-HAART (i.e., 1996 and
      earlier) and HAART eras in Hong Kong. METHODS: The cohort of patients seen at the
      Integrated Treatment Center (Hong Kong) from 1984 through mid-2003 was
      retrospectively examined with respect to 3 clinical end points: death after the
      diagnosis of acquired immunodeficiency syndrome (AIDS), progression to AIDS after
      achieving a CD4 cell count of <200 cells/microL, and death after achieving a CD4
      cell count of <200 cells/microL. RESULTS: A total of 581 patients with advanced
      HIV-1 disease had AIDS and/or a CD4 cell count of <200 cells/microL. The
      incidences of death after AIDS (52.3% vs. 13.6%), AIDS progression after a CD4
      cell count of <200 cells/microL (47.7% vs. 20.9%), and death after a CD4 cell
      count of <200 cells/microL (38.8% vs. 7.0%) were significantly higher among
      patients in the pre-HAART era than among those in the HAART era (P<.001 for all).
      On the basis of life-table analysis, the probabilities of death after AIDS
      (P<.0001), AIDS after a CD4 cell count of <200 cells/microL (P=.0063), and death
      after a CD4 cell count of <200 cells/microL (P<.0001) diminished in the HAART
      era, compared with the pre-HAART era. Median survival after AIDS increased from
      29.8 months during the pre-HAART era to >70 months during the HAART era (P<.001).
      Compared with patients in the pre-HAART era, adjusted hazard ratios of clinical
      events were 0.15 (95% confidence interval [CI], 0.08-0.26) for death after AIDS,
      0.38 (95% CI, 0.24-0.60) for AIDS after a CD4 cell count of <200 cells/microL,
      and 0.25 (95% CI, 0.15-0.40) for death after a CD4 cell count of <200
      cells/microL for patients in the HAART era. CONCLUSIONS. The clinical outcome of
      patients with advanced HIV-1 disease in Hong Kong significantly improved during
      the HAART era. Our findings of extended durations of survival and AIDS-free
      status may be relevant to the expected health impacts associated with increased
      access to HAART in non-Western countries.

PMID- 15472821
TI  - Variable presentation of disseminated nontuberculous mycobacterial infections in
      a family with an interferon-gamma receptor mutation.
AB  - A previously healthy 13-year-old child who had disseminated Mycobacterium avium
      infection is described. Further history revealed disseminated mycobacterial
      infections in the patient's father and uncle, starting at 9 years old and 1 year
      old, respectively. Autosomal dominant interferon- gamma receptor mutation was
      subsequently identified. Clinical variability among the affected members of the
      same family is consistent with previous reports suggesting substantial
      variability in the clinical course of this disorder.

PMID- 15472820
TI  - CCR2 genotype and disease progression in a treated population of HIV type 1
      infected women.
AB  - Both antiretroviral therapy and the human coreceptor polymorphism CCR2-V64I slow
      progression of human immunodeficiency virus type 1 (HIV-1) disease. To examine
      the effect of V64I on disease progression in patients receiving therapy, we
      determined CCR2 genotypes in the Women's Interagency HIV Study cohort. We studied
      2047 HIV-1-infected women, most of whom initiated treatment during the study. No
      association was seen between CCR2 genotype and either disease progression or
      therapeutic response, suggesting that the benefits of treatment most likely
      overshadow the salutary effects of the V64I polymorphism.

PMID- 15472822
TI  - Assessing risk factors for acquiring antimicrobial-resistant pathogens: a time
      for a comparative approach.

PMID- 15472825
TI  - Laboratory diagnosis of urinary tract infections in adult patients.

PMID- 15472827
TI  - No evidence for the effectiveness of ClO2-generating gloves.

PMID- 15472828
TI  - Outbreak of Clostridium difficile infection and gatifloxacin use in a long-term
      care facility.

PMID- 15472830
TI  - Intracellular pharmacology of emtricitabine and tenofovir.

PMID- 15472831
TI  - Antimicrobial mechanisms of cranberry juice.

PMID- 15472833
TI  - Use of the echinocandins (caspofungin) in the treatment of disseminated
      coccidioidomycosis in a renal transplant recipient.

PMID- 15472834
TI  - Three cases of Q fever osteomyelitis in children and a review of the literature.
AB  - Q fever is a common zoonosis worldwide. Awareness of the disease and newer
      diagnostic modalities have resulted in increasing recognition of unusual
      manifestations. We report 3 cases of Q fever osteomyelitis in children and review
      the literature on 11 other reported cases. The cases demonstrate that Coxiella
      burnetii can cause granulomatous osteomyelitis that presents without systemic
      symptoms and frequently results in a chronic, relapsing, multifocal clinical
      course. Optimal selection and duration of antimicrobial therapy and methods of
      monitoring therapy are currently uncertain.

PMID- 15472835
TI  - Conjunctivitis associated with Mycoplasma genitalium infection.
AB  - Conjunctival and first-void urine specimens from a patient with unilateral
      conjunctivitis and urethritis were found to be positive for Mycoplasma genitalium
      but negative for Chlamydia trachomatis, by polymerase chain reaction analysis.
      Identical M. genitalium DNA sequences were found in both types of specimens.

PMID- 15472836
TI  - Native valve endocarditis due to Candida glabrata treated without valvular
      replacement: a potential role for caspofungin in the induction and maintenance
      treatment.
AB  - Conventional antifungal therapy for fungal endocarditis has been associated with
      a poor cure rate. Therefore, combined medical and surgical therapy has been
      recommended. However, new potent antifungal agents, such as echinocandins, could
      increase the medical options and, in some cases, avoid the need for surgery. We
      report a case of Candida endocarditis treated successfully without valve
      replacement with intravenous liposomal amphotericin B (total dose, 4 g) and
      intravenous caspofungin (a 100-mg loading dose followed by 50 mg per day for 8
      weeks) as induction therapy and intravenous caspofungin (100 mg 3 times per week
      for 12 weeks) as maintenance therapy.

PMID- 15472837
TI  - Successful treatment of disseminated nonmeningeal coccidioidomycosis with
      voriconazole.
AB  - A 31-year-old Jamaican man with disseminated nonmeningeal coccidioidomycosis that
      involved the spine, ribs, pelvis, liver, and spleen did not clinically respond to
      a prolonged course of both amphotericin B deoxycholate and liposomal amphotericin
      B therapy. After institution of voriconazole monotherapy, the patient had a
      favorable (albeit slow) radiological and clinical response without adjunctive
      surgical intervention.

PMID- 15472838
TI  - Diagnosis and treatment of diabetic foot infections.

PMID- 15472839
TI  - Nasopharyngeal pneumococcal carriage after combined pneumococcal conjugate and
      polysaccharide vaccination in children with a history of recurrent acute otitis
      media.
AB  - BACKGROUND: We recently showed that vaccination with a 7-valent pneumococcal
      conjugate vaccine (PCV7) followed by a 23-valent pneumococcal polysaccharide
      vaccine (PPSV23) failed to prevent new episodes of acute otitis media (AOM) in
      previously unvaccinated toddlers and children with a history of recurrent AOM. We
      describe in detail the impact of pneumococcal vaccinations on nasopharyngeal
      carriage of S. pneumoniae in this study population. METHODS: The impact of
      vaccination with PCV7 followed by PPSV23 on pneumococcal nasopharyngeal carriage
      was studied in a prospective, randomized trial involving 383 children (age range,
      1-7 years) with previous AOM. Nasopharyngeal swab specimens were collected at the
      time of first vaccination and at 6-7-month intervals during the 26-month follow
      up period. RESULTS: Overall, pneumococcal carriage rates did not diminish,
      remaining at approximately 50% in both PCV7/PPSV23 and control vaccinees. A
      significant shift from conjugate vaccine- to nonconjugate vaccine-type
      pneumococci was observed in children aged 1-2 years, who received the conjugate
      vaccine twice before the polysaccharide vaccine was administered. Conjugate
      vaccine serotype carriage was not influenced in older children, who received the
      conjugate vaccine once before receiving the polysaccharide booster. CONCLUSIONS:
      The administration of conjugate vaccines at least twice also after 2 years of age
      may be mandatory for reducing the carriage of conjugate vaccine serotypes in
      children with recurrent AOM. Polysaccharide booster vaccination did not affect
      nasopharyngeal colonization with serotypes not included in the conjugate vaccine.

PMID- 15472840
TI  - Safety, efficacy, and effectiveness of live, attenuated, cold-adapted influenza
      vaccine in an indicated population aged 5-49 years.
AB  - BACKGROUND: Three important studies have supported licensure of live, attenuated,
      cold-adapted influenza vaccine (CAIV-T [FluMist; MedImmune Vaccines]): (1) a
      pediatric efficacy trial involving children 15-71 months of age, (2) a large
      safety study of medically attended events occurring among children 1-17 years of
      age, and (3) an effectiveness trial involving healthy working adults 18-64 years
      of age. METHODS: During the United States Food and Drug Administration (FDA)
      review for the approval of CAIV-T for use in healthy persons, additional subgroup
      analyses were conducted to evaluate the safety, efficacy, and effectiveness of
      the vaccine, by use of various age subsets not prespecified by the original
      protocols. CAIV-T is currently approved by the FDA for use in healthy persons 5
      49 years of age. In this article, we present data from some of the aforementioned
      subanalyses. RESULTS: The efficacy of CAIV-T in children >or=5 years of age (age
      range of the children in year 1 of the study, 60-71 months; age range of the
      children in year 2 of the study, 60-83 months) was similar to that reported for
      the entire cohort in year 1 (90.6%; 95% confidence interval [CI], 70.3%-97.1%).
      In year 2 of the study, efficacy was 86.9% (95% CI, 70.8%-94.1%), despite the
      presence of antigenically drifted influenza type A/Sydney/5/97 (H3N2), which
      caused most illnesses that occurred in year 2. Safety outcomes for children 5-17
      years of age revealed no significant difference between vaccine recipients and
      placebo recipients, with regard to acute respiratory events, acute
      gastrointestinal events, systemic bacterial infection, or rare events possibly
      related to influenza. Effectiveness among adults 18-49 years of age was similar
      to that reported for the entire cohort--for example, for occurrence of severe
      febrile illness, there was a 19.5% reduction (P=.02) in adults. CONCLUSIONS: The
      present reanalysis summarizes data on the indicated uses for CAIV-T in the
      indicated population aged 5-49 years.

PMID- 15472841
TI  - How do influenza vaccines work?

PMID- 15472842
TI  - Effect of the 7-valent pneumococcal conjugate vaccine on nasopharyngeal
      colonization by Streptococcus pneumoniae in the first 2 years of life.
AB  - BACKGROUND: Studies suggest that the 7-valent pneumococcal conjugate vaccine
      (PCV7) reduces carriage of vaccine-type (VT) Streptococcus pneumoniae (SP). We
      studied the effect of PCV7 on carriage of VT- and non-VT (NVT) SP, by studying
      the effect of PCV7 on nasopharyngeal (NP) colonization by VT and NVT SP during
      early childhood. METHODS: At 2 months of age, 278 infants were enrolled in this
      study. To determine carriage of SP, NP samples were obtained before each PCV7
      dose, at 9 months of age, and 2-3 months after the booster dose of vaccine.
      RESULTS: The carriage of SP increased slightly, from 12% (95% confidence interval
      [CI], 8%-16%) of subjects at 2 months of age to 18% (95% CI, 13%-23%) at 4 months
      of age (P<.05). Carriage of SP remained in 24%-30% of subjects during subsequent
      months. Between the 12- and 18-month visits, the carriage rate of VT SP decreased
      significantly, from 18% (95% CI, 13%-23%) to 9% (95% CI, 5%-13%) of subjects
      (P=.001). The trend of a decrease in carriage of penicillin-nonsusceptible SP,
      from 16% of subjects (95% CI, 11%-21%) at the 12-15-month visit to 9% (95% CI, 5%
      13%) at the 15-18-month visit, was found after the booster dose of vaccine.
      CONCLUSION: The reduction of VT-SP colonization and replacement by NVT SP after
      the booster dose of vaccine suggests the possibility that widespread vaccination
      will result in replacement of pneumococci mainly by antibiotic-susceptible NVT
      SP.

PMID- 15472843
TI  - Clinical characteristics of patients in Peru with human T cell lymphotropic virus
      type 1-associated tropical spastic paraparesis.
AB  - BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1) is associated with
      tropical spastic paraparesis (TSP). Peru is an area of endemicity for HTLV-1.
      METHODS: All patients with suspected cases of TSP referred to our institute
      (Institute of Tropical Medicine Alexander von Humboldt, Lima, Peru) from 1989
      through 2002 were interviewed and tested for HTLV-1. All patients with positive
      results were evaluated by an expert physician. Disease progression was defined as
      "rapid" if the time between TSP onset and inability to walk unaided was <2 years.
      RESULTS: Among 165 patients enrolled, the symptoms and signs most frequently
      found were spasticity (in 97.5% of patients), hyperreflexia (95.4%), lower limb
      paresthesia (90.2%), pyramidal signs (82.6%), urinary complaints (82.0%), and
      lumbar pain (79.0%). Rapid progression was present in 21.5% of patients; mean age
      at TSP onset was higher among these patients than among slow progressors
      (P<.001). Severe spasticity, diminished vibratory sensation, and tremor were
      found more frequently among rapid progressors, compared with slow progressors.
      CONCLUSIONS: HTLV-1--associated TSP is frequently diagnosed in areas of HTLV-1
      endemicity. A subgroup of patients experiences rapid disease progression.

PMID- 15472844
TI  - Widespread dissemination in England of a stable and persistent hepatitis B virus
      variant.
AB  - BACKGROUND: Outbreaks of acute hepatitis B among inmates of 6 prisons in 3
      regions of northern England occurring from 1992 through 1994 were found to be
      associated with a single hepatitis B virus (HBV) variant, which was carried by 20
      of the 24 case patients. We instigated a study of cases of acute hepatitis B to
      trace the spread and prevalence of this variant. METHODS: A denaturing gradient
      gel electrophoresis assay was optimized to detect the HBV variant, and cases of
      acute HBV infection in 3 regions in England occurring from 1990 through 1996 were
      screened for its presence. Samples from HBV-transmission incidents that were
      received for molecular investigation were also tested. RESULTS: The variant was
      identified in 117 (41%) of the 266 cases of acute hepatitis examined in
      representative regions in England. In North Humberside, but not in southeast
      England or the West Midlands, a trend toward an increase in the prevalence of the
      variant was observed. Furthermore, the same variant was identified in the case
      patients or the individuals implicated in transmission in 11 (22%) of 51
      transmission incidents occurring in England from 1997 through 2002. The spread of
      the variant was primarily associated with injection drug use. CONCLUSIONS: The
      finding of a single, genetically identical variant (over the 600 bp sequenced)
      occupying a large niche among the circulating viruses was unexpected. This
      finding has major implications for the use of DNA sequencing analysis in the
      investigation of chains of transmission. The study also highlights the need for
      better protection of at-risk groups through vaccination against HBV, a strategy
      that currently achieves poor coverage.

PMID- 15472845
TI  - Surveillance of the molecular epidemiology of hepatitis B virus in industrialized
      countries: necessary despite low prevalence and an available, effective vaccine?

PMID- 15472846
TI  - Improvement of process-of-care and outcomes after implementing a guideline for
      the management of community-acquired pneumonia: a controlled before-and-after
      design study.
AB  - BACKGROUND: Studies investigating the impact of guideline implementation for
      inpatient management of community-acquired pneumonia (CAP) usually have
      methodological limitations. We present a controlled study that compared
      interventions before and after the implementation of a practice guideline.
      METHODS: Clinical and demographic characteristics, as well as process-of-care and
      outcome indicators, were recorded for all patients with CAP who were admitted to
      Galdakao Hospital (Galdakao, Spain) in the 19-month period after the
      implementation, on 1 March 2000, of a guideline for the treatment of CAP. These
      data were also recorded for all patients with CAP who were admitted to this
      hospital during the year before the guideline was implemented, as well as for
      randomly selected inpatients with CAP at 4 other hospitals during both periods
      (i.e., before and after guideline implementation) who were chosen as an external
      comparison group. Multivariate linear and logistic regression models were
      employed for adjustment. RESULTS: Guideline implementation resulted in shorter
      durations of antibiotic treatment (P<.001) and intravenous treatment (P<.001),
      better coverage of atypical pathogens (P<.001), and improved appropriateness of
      antibiotic treatment (P<.001), compared with the period before the guideline was
      implemented. The adjusted analyses revealed decreases in 30-day mortality (odds
      ratio [OR], 2.14; 95% confidence interval [CI], 1.23-3.72) and in-hospital
      mortality (OR, 2.46; 95% CI, 1.37-4.41) and a 1.8-day reduction in the duration
      of hospital stay. In the control hospitals, there were small but statistically
      insignificant changes in these indicators for admitted patients. CONCLUSIONS:
      This study, which was performed with an adequate, controlled before-and-after
      intervention design, demonstrated significant improvements in both process-of
      care and outcome indicators after implementation of a guideline for treating CAP.

PMID- 15472847
TI  - Preventing the influx of vancomycin-resistant enterococci into health care
      institutions, by use of a simple validated prediction rule.
AB  - BACKGROUND: The goal of this study was to develop a validated prediction rule for
      identification of patients harboring vancomycin-resistant enterococci (VRE) at
      hospital admission. METHODS: A model for the prediction of patients harboring VRE
      at admission was created and validated by assigning weighted point values to
      independent risk factors associated with harboring VRE at admission, in 2
      different cohorts of patients from 2 tertiary care hospitals in Boston,
      Massachusetts. Patients with VRE isolated from clinical culture samples collected
      within 48 h of hospital admission were compared with patients not harboring VRE.
      To assess the diagnostic accuracy of the prediction rule, the main outcome
      measures were patient demographic characteristics, comorbid illnesses,
      hospitalizations, and antibiotic exposure. RESULTS: A total of 412 patients were
      enrolled. A risk index score was derived by using the following 6 independent
      risk factors associated with VRE recovery within 48 h of hospital admission:
      previous isolation of methicillin-resistant Staphylococcus aureus (MRSA), whether
      the patient was receiving long-term hemodialysis, transfer from a long-term care
      facility, antibiotic exposure, prior hospitalization, and age >60 years. On the
      basis of a point score >or=10, the sensitivity, specificity, and positive and
      negative predictive values of this prediction rule were 44%, 98%, 81%, and 90%,
      respectively. CONCLUSIONS: This validated clinical prediction rule provides a
      novel strategy for the identification of patients at high risk of harboring VRE
      at hospital admission. Implementation of this rule may reduce the influx of VRE
      into health care institutions and the overall prevalence of VRE, by targeting VRE
      screening measures and contact isolation precautions for these high-risk
      patients.

PMID- 15472848
TI  - Natural history of community-acquired methicillin-resistant Staphylococcus aureus
      colonization and infection in soldiers.
AB  - BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus (CA
      MRSA) is an emerging pathogen for which the prevalence, risk factors, and natural
      history are incompletely understood. METHODS: In this prospective observational
      study, we evaluated 812 US Army soldiers to determine the prevalence of and risk
      factors for CA-MRSA colonization and the changes in colonization rate over time,
      as well as to determine the clinical significance of CA-MRSA colonization.
      Demographic data and swab samples from the nares for S. aureus cultures were
      obtained from participants at the start of their training and 8-10 weeks later.
      Over this time period, participants were observed prospectively to monitor for
      soft-tissue infections. S. aureus isolates were characterized by in vitro
      examination of antibiotic susceptibilities, mecA confirmation, pulsed-field gel
      electrophoresis, and Panton-Valentine leukocidin (PVL) gene testing. RESULTS: At
      the initial sampling, 24 of the participants (3%) were colonized with CA-MRSA, 9
      of whom (38%) developed soft-tissue infections during the study period. In
      contrast, 229 participants (28%) were colonized with methicillin-susceptible S.
      aureus (MSSA), 8 (3%) of whom developed clinical infections during the same
      period (relative risk, 10.7; 95% confidence interval, 4.6-25.2; P<.001). At
      follow-up culture, the CA-MRSA colonization rate dropped to 1.6% without
      eradication efforts. Previous antibiotic use was a risk factor for CA-MRSA
      colonization at the initial sampling (P=.03). PVL genes were detected in 66% of
      45 recovered CA-MRSA isolates, including all 9 clinical isolates available for
      analysis. Of subjects hospitalized, 5 of 6 had PVL-positive CA-MRSA infections.
      CONCLUSIONS: CA-MRSA colonization with PVL-positive strains was associated with a
      significant risk of soft-tissue infection, suggesting that CA-MRSA may be more
      virulent than MSSA. Previous antibiotic use may play a role in CA-MRSA
      colonization.

PMID- 15472849
TI  - Clinical predictors of bacterial involvement in exacerbations of chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: The wide use of antibiotics for treatment of exacerbations of chronic
      obstructive pulmonary disease (COPD) lacks evidence. The efficacy is debatable,
      and bacterial involvement in exacerbation is difficult to verify. The aim of this
      prospective study was to identify factors that can help to estimate the
      probability that a microorganism is involved in exacerbation of COPD and,
      therefore, predict the success of antibiotic treatment. METHODS: Clinical data
      and sputum samples were obtained from 116 patients during exacerbation of COPD.
      Bacterial infection was defined by the abundant presence of >or=1 potential
      pathological microorganism in relation to the normal flora in sputum. RESULTS: Of
      116 exacerbations, 22 (19%) had bacterial involvement. The combination of a
      negative result of a sputum Gram stain, a relevant nonclinical decrease in lung
      function (compared with baseline measurements), and occurrence of <2
      exacerbations in the previous year were 100% predictive of a nonbacterial origin
      of the exacerbation. The presence of all 3 of these clinical characteristics
      yielded a positive predictive value of 67% for a bacterial exacerbation.
      CONCLUSIONS: Patients presenting with an exacerbation who have a negative result
      of sputum Gram stain, do not have a clinically relevant decrease in lung
      function, and have experienced <2 exacerbations of COPD in the previous year do
      not require antibiotic treatment [corrected]. A treatment protocol taking into
      account these variables might lead to a 5%-24% reduction in unnecessary treatment
      with antibiotics, depending on actual prescription rates.

PMID- 15472850
TI  - Who should receive antibiotics for exacerbations of chronic bronchitis? A plea
      for more outcome-based studies.

PMID- 15472851
TI  - Bacterial vaginosis and anaerobic bacteria are associated with endometritis.
AB  - BACKGROUND: Chlamydia trachomatis and/or Neisseria gonorrhoeae account for
      approximately one-third to one-half of pelvic inflammatory disease (PID) cases.
      Thus, up to 70% of cases have an unknown, nongonococcal/nonchlamydial microbial
      etiology. METHODS: We investigated the associations of N. gonorrhoeae, C.
      trachomatis, bacterial vaginosis, anaerobic bacteria, facultative bacteria, and
      lactobacilli with endometritis among 278 women with complete endometrial
      histology and culture from the PID Evaluation and Clinical Health Study. RESULTS:
      Women with acute endometritis were less likely to have H(2)O(2)-producing
      Lactobacillus species (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.01
      0.8) and more likely to be infected with C. trachomatis (OR, 16.2; 95% CI, 4.6
      56.6), N. gonorrhoeae (OR, 11.6; 95% CI, 4.5-29.9), diphtheroids (OR, 5.0; 95%
      CI, 2.1-12.2), black-pigmented gram-negative rods (OR, 3.1; 95% CI, 1.4-7.0), and
      anaerobic gram-positive cocci (OR, 2.1; 95% CI, 1.0-4.3) and to have bacterial
      vaginosis (OR, 2.4; 95% CI, 1.3-4.3). CONCLUSIONS: We conclude that bacterial
      vaginosis-associated organisms are frequent among women with PID. Because these
      organisms were strongly associated with endometritis, we recommend that all women
      with PID be treated with regimens that include metronidazole.

PMID- 15472852
TI  - Resurgence of lymphogranuloma venereum in Western Europe: an outbreak of
      Chlamydia trachomatis serovar l2 proctitis in The Netherlands among men who have
      sex with men.
AB  - BACKGROUND: Lymphogranuloma venereum (LGV) is a sexually transmitted disease
      (STD) and is rare in the Western world. Recently, 3 men who have sex with men
      presented with LGV proctitis at the Erasmus Medical Center, Rotterdam, The
      Netherlands. We investigated a possible outbreak in a sexual network of men who
      have sex with men (MSM). METHODS: After active case finding, a total of 15 men
      presented and were investigated. Serum antibody titers to Chlamydia trachomatis
      were determined. Urine and rectum specimens were analyzed by polymerase chain
      reaction (PCR) for the presence of C. trachomatis. C. trachomatis-positive
      specimens were genotyped to detect the specific C. trachomatis serovars. All
      subjects underwent routine STD screening. Sociodemographic, clinical, and
      endoscopic characteristics were evaluated. RESULTS: Thirteen subjects had high
      immunoglobulin (Ig) G and IgA titers to C. trachomatis, suggesting an invasive
      infection. Rectal specimens of 12 subjects were PCR-positive for C. trachomatis.
      All urine specimens were negative. Genotyping revealed serovars L(2) (n=8) and
      L(1) (n=1). An ulcerative proctitis was found in all subjects obtaining
      sigmoidoscopy (n=9). Eleven of 13 subjects with an LGV diagnosis were
      seropositive for human immunodeficiency virus (HIV), 6 had another concomitant
      STD, and 1 had recently acquired a hepatitis C virus infection. Further sexual
      contacts were reported from The Netherlands, Germany, Belgium, the United
      Kingdom, and France. CONCLUSIONS: We revealed an outbreak of LGV proctitis among
      MSM in The Netherlands. The ulcerous character favors transmission of HIV, other
      STDs, and blood-borne diseases. From a public health perspective, it seems
      important to increase the awareness of possible LGV in MSM with symptomatic
      proctitis.

PMID- 15472853
TI  - Randomized trial comparing vaccinia on the external surfaces of 3 conventional
      bandages applied to smallpox vaccination sites in primary vaccinees.
AB  - BACKGROUND: Concern about accidental contact transmission after smallpox
      vaccination has prompted various recommendations regarding vaccination site
      coverage. METHODS: On days 6-8 after their first-ever smallpox vaccination, 63
      adult subjects were randomized to apply a self-adhesive bandage (n=20), gauze
      with adhesive tape (n=21), or gauze with a semipermeable dressing (n=22) over the
      vaccination site for a mean of 8+/-2 h. Swabs from the external bandage surfaces
      and the vaccination sites were then assessed by real time vaccinia-specific
      polymerase chain reaction (PCR) in blinded fashion. RESULTS: Among 58 subjects
      completing the study, PCR results were positive for the vaccination site in 55
      (94.8%) and on 10 swabs (17.2%) from external bandage surfaces. There were no
      differences among the 3 bandages (P=.57). CONCLUSIONS: At 7 days after smallpox
      vaccination, a peak time for vaccinia shedding, a self-adhesive bandage was as
      effective as 2 bulkier, less convenient bandages in limiting PCR-detectable virus
      on the external surface.

PMID- 15472854
TI  - Antimicrobial resistance to linezolid.
AB  - Acquired resistance to linezolid, the first approved oxazolidinone, has been
      selected in laboratory experiments and has been observed in clinical isolates of
      gram-positive cocci. This resistance has typically been associated with single
      nucleotide changes in varying numbers of copies of the genes encoding 23S
      ribosomal RNA. In the current environment of increasingly prevalent resistance to
      standard antibiotics, linezolid is an important drug because of its activity
      against a number of clinically significant gram-positive cocci, including
      multidrug-resistant staphylococci and enterococci. Although resistance to
      linezolid remains uncommon, the development of resistance by clinical isolates
      should prompt increased attention to susceptibility testing for this agent and
      should be taken into account in consideration of the therapeutic use of this
      drug.

PMID- 15472855
TI  - New developments in the diagnosis and management of posttransplantation
      lymphoproliferative disorders in solid organ transplant recipients.
AB  - Posttransplantation lymphoproliferative disorders (PTLDs) have emerged as
      important causes of morbidity and mortality in solid organ transplant recipients.
      Epstein-Barr virus (EBV) plays a major pathophysiologic role in the development
      of many, if not most, of the highly diverse disease states, which span the
      spectrum from infection to malignancy, encompassed by the term "PTLD." Clinical
      presentation and biological behavior associated with PTLD are highly variable;
      patients experiencing primary EBV infection in the immediate posttransplantation
      period are most vulnerable. New insights into PTLD pathogenesis provide exciting
      opportunities for rational and targeted approaches to the diagnosis, prevention,
      and treatment of PTLD. This article highlights some of these developments and
      outlines unresolved and controversial issues in PTLD management.

PMID- 15472856
TI  - Long-term efficacy and safety of protease inhibitor switching to nevirapine in
      HIV-infected patients with undetectable virus load.
AB  - BACKGROUND: Simplified highly active antiretroviral therapy (HAART) regimens are
      becoming widely used, particularly as a result of the side effects of and
      difficult compliance with protease inhibitor (PI) therapy. However, the long-term
      efficacy of HAART has not been properly assessed. METHODS: We performed a
      prospective study of 110 patients infected with human immunodeficiency virus type
      1 (HIV-1) with undetectable virus load who discontinued PI therapy and initiated
      therapy with nevirapine without changing nucleoside analogues. Reasons for
      switching were treatment simplification (45%), lipodystrophy (24%), renal
      problems (23%), and dyslipidemia (8%). HIV-1 load, CD4 cell count, and fasting
      biochemistry profiles were performed at the time of switching (baseline) and
      every 3-4 months thereafter. The aim of the study was to evaluate the long-term
      efficacy and safety of this combination. RESULTS: Sixty-eight patients (61.8%)
      had a duration of follow-up of 3 years. The mean increase in the CD4 cell count
      after 3 years was 90 cells/microL (13.8% from baseline). Virus loads remained
      undetectable in all patients but 9 (8.2%). Triglyceride levels dramatically
      improved at 12 months (a 75% decrease; P<.02) and remained statistically
      significant over time (P<.04). The same occurred with serum cholesterol levels:
      there was an initial reduction of 25% (P<.02) and at the end of the follow-up
      period (P<.015). However, at the long-term evaluation, complete normalization of
      mean serum cholesterol and triglyceride levels could not be achieved. Sixteen
      patients (14.5%) had to stop therapy as a result of nevirapine-associated side
      effects. CONCLUSIONS: The switching of a PI to nevirapine is a safe and well
      tolerated option for maintaining long-term virological suppression and
      immunological control. Three years after starting nevirapine therapy, rates of
      hypercholesterolemia and hypertriglyceridemia improved, although normal
      cholesterol and triglyceride values were not achieved.

PMID- 15472857
TI  - Genotypic resistance in HIV-1-infected patients with persistently detectable low
      level viremia while receiving highly active antiretroviral therapy.
AB  - BACKGROUND: Technical limitations in the sensitivity of commercial genotyping
      methods may prevent clinicians from determining whether drug-resistant human
      immunodeficiency virus type 1 (HIV-1) is present in patients with low-level
      viremia. We performed ultrasensitive HIV-1 genotyping for patients with
      persistent plasma virus loads of 50-400 copies/mL to better define the prevalence
      of drug resistance and the most common resistance mutations during persistently
      detectable low-level viremia. METHODS: Genotyping of HIV-1 was performed with an
      ultrasensitive clonal genotyping method. RESULTS: We studied 21 patients who had
      persistent, detectable, low-level viremia for a median of 11 months. Nine (43%)
      of 21 patients had HIV-1 isolates with significant resistance mutations. The most
      common mutations were M184V, K65R, and M41L/T215Y. CONCLUSIONS: The finding that
      clinically significant resistance mutations were present in some but not all
      patients with persistent viremia (range, 50-400 copies/mL) highlights the need to
      improve the sensitivity of current clinical assays for detection of drug
      resistance.

PMID- 15472858
TI  - Abacavir versus zidovudine combined with lamivudine and efavirenz, for the
      treatment of antiretroviral-naive HIV-infected adults.
AB  - BACKGROUND: Zidovudine, lamivudine, and efavirenz comprise a highly effective and
      well-tolerated triple regimen for antiretroviral-naive patients. Evaluating other
      unique nucleoside reverse-transcriptase inhibitor (NRTI) combinations for long
      term viral suppression is desirable. METHODS: This multicenter, randomized,
      double-blind noninferiority clinical trial compared the efficacy and safety of
      abacavir with that of zidovudine plus lamivudine and efavirenz in 649
      antiretroviral-naive HIV-infected patients. The primary objective was a
      comparison of proportions of patients achieving plasma HIV-1 RNA levels <or=50
      copies/mL through week 48 of the study. RESULTS: At study week 48, 70% of
      patients in the abacavir group, compared with 69% in the zidovudine group,
      maintained confirmed plasma HIV-1 RNA levels of <or=50 copies/mL (in the intent
      to-treat exposed population). Virologic failure was infrequent (6% in the
      abacavir group and 4% in the zidovudine group). There was a significant CD4(+)
      cell response (209 cells/mm(3) in the abacavir group and 155 cells/mm(3) in the
      zidovudine group). Safety profiles were as expected. CONCLUSION: Abacavir
      provided an effective and durable antiretroviral response that was noninferior to
      zidovudine, when combined with lamivudine and efavirenz.

PMID- 15472859
TI  - Prevalence of dihydropteroate synthase mutants in HIV-infected South African
      children with Pneumocystis jiroveci pneumonia.
AB  - BACKGROUND: Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP)
      is a major cause of mortality in human immunodeficiency virus (HIV)-infected
      infants in Africa, but the prevalence of mutations in the gene encoding
      dihydropteroate synthase (DHPS) in isolates from Africa has not been reported.
      METHODS: This study investigated the prevalence of DHPS mutations in P. jiroveci
      isolates from South African HIV-infected children with PCP by amplifying DNA
      using 2 different polymerase chain reactions. RESULTS: P. jiroveci DNA from 30
      respiratory specimens was amplified; 26 specimens (86.7%) contained wild-type
      DHPS alleles. Of the 4 samples (13.3%) with DHPS mutations, 2 contained a
      homogenous population with single DHPS mutations, 1 contained a homogenous
      population with 2 DHPS mutations, and the fourth contained a heterogenous
      population of organisms with both wild-type and single-mutant DHPS genotypes.
      Only 1 child was receiving trimethoprim-sulphamethoxazole (TMP-SMZ) prophylaxis;
      this patient was infected with wild-type P. jiroveci. The mortality rate
      (overall, 20 [66.7%] of 30 children) was not significantly different between
      children infected with wild-type P. jiroveci (17 [65.4%] of 26) and those
      infected with mutant strains (3 [75%] of 4; P=.8). CONCLUSIONS: DHPS mutations
      are uncommon in P. jiroveci isolates from South Africa. However, increasing use
      of TMP-SMZ prophylaxis may result in widespread development of mutations.

PMID- 15472861
TI  - Crazy 8: unraveling human herpesvirus 8 seroprevalence.

PMID- 15472860
TI  - Seroprevalence of human herpesvirus 8 infection in Northern Thailand.
AB  - BACKGROUND: Human herpesvirus 8 (HHV-8) is associated with Kaposi sarcoma (KS) in
      patients with acquired immunodeficiency syndrome (AIDS) and KS, classical KS, or
      endemic KS. Because human immunodeficiency virus (HIV) infections and HIV/AIDS
      are common in Thailand but KS is very rare (only 0.2% of reported patients with
      AIDS in Thailand had KS), we determined the HHV-8 seroprevalence among
      populations who were HIV positive or at risk of HIV infection. METHODS: A total
      of 992 persons from 2 populations underwent testing for lytic antibodies to HHV-8
      using an immunofluorescence assay involving a BCBL-1 cell line at serum dilutions
      of 1 : 50 and 1 : 100. Serum specimens with positive results were titered to end
      points. Subjects included approximately 400 married couples in which the husband
      was HIV positive and the wife was HIV positive (200 couples) or HIV negative (200
      couples). In addition, 200 HIV-negative men from a sexually transmitted diseases
      (STD) clinic were studied. RESULTS: The antibody prevalence was 24.2% in the
      total population. The prevalence was higher among HIV-negative men (13.0%) but
      was similar among HIV-positive women (27.9%) and HIV-negative women (23.8%). The
      HHV-8 seroprevalence among wives whose husbands were HIV-1 positive did not
      differ according to their husband's HHV-8 status. There was no association
      between HHV-8 seroprevalence and reported sexual behavior or STD history.
      CONCLUSION: Despite the rarity of KS among patients with AIDS in Thailand, HHV-8
      infections are common and do not appear to be frequently transmitted sexually in
      these populations.

PMID- 15472862
TI  - Ninety-six-week efficacy of combination therapy with lamivudine and tenofovir in
      patients coinfected with HIV-1 and wild-type hepatitis B virus.
AB  - We describe 6 patients who were coinfected with human immunodeficiency virus
      (HIV) type 1 and wild-type hepatitis B virus (HBV), in whom complete and
      sustained antiviral activity against wild-type HBV strains was attained during 96
      weeks of combination therapy with lamivudine and tenofovir. The use of
      combination therapy with lamivudine and tenofovir for the treatment of HBV
      infection is very promising in the treatment of HIV/HBV coinfection.

PMID- 15472863
TI  - Presurgical maggot debridement of soft tissue wounds is associated with decreased
      rates of postoperative infection.
AB  - Postoperative complications were assessed for all patients who received
      presurgical maggot debridement therapy (MDT) and for a matched group of patients
      who did not. Ten wounds were debrided by maggots within 1-17 days prior to
      surgical closure. Debridement was effective in all cases, and there were no
      postoperative wound infections. Six (32%) of 19 wounds not treated presurgically
      with MDT developed postoperative wound infections (95% CI, 10%-54%; P<.05).
      Presurgical MDT was effective in preparing the wound bed for surgical closure,
      without increased risk of postsurgical wound infection.

PMID- 15472864
TI  - Temporal relationship of viral load, ribavirin, interleukin (IL)-6, IL-8, and
      clinical progression in patients with severe acute respiratory syndrome.
AB  - Although viral replication and overwhelming immune responses are believed to
      contribute to the progression of severe acute respiratory syndrome (SARS), little
      is known about the temporal relationship between viral load, ribavirin,
      proinflammatory cytokines, and clinical progression. We report that ribavirin was
      not effective in reducing the SARS coronavirus load in 3 of 8 probable cases
      studied and that elevated levels of interleukin (IL)-6 and IL-8 subsequent to the
      peak viral load were found in 8 and 6 cases, respectively. The nadir lymphocyte
      count during lymphopenia, the peak level of lactate dehydrogenase, and the peak
      density of pulmonary infiltrates lag further behind the peak viral load by a
      median of 4, 5, and 3.5 days, respectively. These findings provide important
      information for therapeutic strategies to treat SARS.

PMID- 15472865
TI  - Early-onset Guillain-Barre syndrome associated with reactivation of Epstein-Barr
      virus infection after nonmyeloablative stem cell transplantation.
AB  - We report a case of early-onset acute Guillain-Barre syndrome associated with
      reactivation of Epstein-Barr virus (EBV) infection after nonmyeloablative stem
      cell transplantation (NST). Reactivation of EBV infection preceded disease onset,
      and the virus load increased concomitantly with disease progression (doubling
      time, 2.7 days). This case raises concern about the expanding scope of
      manifestations associated with reactivation of EBV infection after NST.

PMID- 15472866
TI  - Human T cell lymphotropic virus type 1 infection and early neurologic
      development: a pilot study of 48 children.
AB  - To determine whether human T cell lymphotropic virus type 1 (HTLV-1) infection is
      associated with delayed neurological development, we examined 48 Peruvian
      children with exposure to HTLV-1 who were identified at the Instituto Materno
      Perinatal. Compared with 38 HTLV-1-seronegative children, the 10 seropositive
      children did not have higher rates of neurodevelopmental delay. Long-term follow
      up is planned.

PMID- 15472867
TI  - Hepatic safety and postexposure prophylaxis.

PMID- 15472868
TI  - Broadened definition for hospital-acquired infective endocarditis.

PMID- 15472871
TI  - Antemortem diagnosis of human rabies.

PMID- 15472872
TI  - Infection by drug-resistant Streptococcus pneumoniae is not linked to increased
      mortality.

PMID- 15472874
TI  - Visceral leishmaniasis as a cause of anemia in HIV-infected patients.

PMID- 15472877
TI  - Differentiating pain and delirium is only part of assessing the agitated child.

PMID- 15472879
TI  - Managing do-not-resuscitate orders in the perianesthesia period.
AB  - Perianesthesia care often involves the use of pharmacologically potent drugs,
      increasing the risk of cardiopulmonary depression and arrest. For patients with
      terminal diseases, it may be difficult to decide whether cardiopulmonary arrest
      in the perianesthesia period is a result of anesthetic medications, surgical
      intervention, or the disease process. It is imperative that the patient maintains
      autonomy and is treated according to his or her wishes regarding do-not
      resuscitate (DNR) orders. Some hospitals automatically suspend DNR orders for
      patients undergoing surgery, whereas others provide patients the option of no,
      limited, or full resuscitation. This article promotes the premise that all DNR
      orders should be reviewed and reconsidered with patients before consent for
      surgery.

PMID- 15472880
TI  - The alarming trend of substance abuse in anesthesia providers.
AB  - The role of the anesthesia provider requires a high level of awareness and
      constant vigilance. Literature indicates, however, that the substance abuse rate
      in certified registered nurse anesthetists (CRNAs) and anesthesiologists has
      reached staggering levels. The literature also shows that there has been a change
      in which controlled drugs are being misused. It is imperative that perianesthesia
      nurses be aware of the current problem and take steps when indicated to protect
      both providers and patients. This article discusses the current trends of
      addiction in anesthesia providers, treatment, and reentry, as well as the role of
      the perianesthesia nurse in recognizing, reporting, and preventing substance
      abuse.

PMID- 15472881
TI  - Managing acute postoperative pain: is 3 hours too long?
AB  - This case study discusses a 64-year-old opioid-tolerant patient who underwent
      amputation below the left knee and received pain management in the PACU. The
      patient's self-reported pain level remained 9 on a 0 to 10 scale despite having
      received a total of 62 mg of morphine sulfate (MSO 4 ) and 60 mg of ketorolac in
      just less than 3 hours. The patient's facial expression corresponded to a score
      of 4 to 5 based on the Wong-Baker Faces Pain Scale. This case study illustrates
      that it is crucial to promptly involve the pain management service when an opioid
      tolerant patient requires aggressive pain treatment. The initial patient
      controlled analgesia (PCA) order and MSO 4 -loading doses must take into account
      the patient history of opioid tolerance, increasing the frequency and dosage
      loading doses of MSO 4 for treating severe pain until the patient's pain is
      reduced by at least 50% on a numeric scale, or until the patient states
      satisfactory relief. The most important rule of pain management is that pain is
      what the patient says it is.

PMID- 15472882
TI  - Primary hyperparathyroidism: a case study.
AB  - Primary hyperparathyroidism is a hypercalcemic condition generated as a result of
      overproduction of parathyroid hormone (PTH) by one or more of the parathyroid
      glands. The cause is usually an abnormal group of cells forming a benign adenoma
      and rarely carcinoma. The condition is usually discovered by routine serum
      chemistry analysis showing hypercalcemia, hypophosphatemia, and elevated PTH
      levels. Elevated 24-hour urine calcium provides further confirmation. During the
      last decade, three procedures have been developed to help diagnose the affected
      parathyroid gland(s) in preparation for surgical intervention: computerized
      nuclear scanning with technetium-99-m sestamibi performed preoperatively; radio
      guided probes; and rapid PTH assay (RPHA), both used intraoperatively. These
      three techniques have been reported to reduce the need for immediate frozen
      section diagnosis; shorten the length of the incision, surgical time, and length
      of hospital stay; produce less pain and discomfort; reduce surgical cost; and
      produce a quicker return to normal life. This article follows the surgical
      experience of a patient with a diagnosis of hyperparathyroidism and a history of
      postoperative nausea and vomiting who was scheduled as 23-hour stay.

PMID- 15472883
TI  - The selection process: interview tips for nurse managers.

PMID- 15472884
TI  - Universal protocol for preventing wrong site, wrong procedure, wrong person
      surgery.

PMID- 15472885
TI  - Interscalene blocks: care in the ambulatory setting.

PMID- 15472887
TI  - Data mining: an excellent research tool.

PMID- 15472889
TI  - Nurses, caring, and politics: care enough to vote.

PMID- 15472890
TI  - Development of ecological competence in Sumatran orangutans.
AB  - Data on orangutans (Pongo pygmaeus abelii) living in a Sumatran swamp forest
      yield an estimated median interbirth interval of at least 8 years, concurring
      with findings from other sites. This longest known mammalian interbirth interval
      appears due to maternal amenorrhea during the long exclusive dependence of the
      offspring. We describe the development of various components of offspring
      independence. In this arboreal ape, 3-year-olds had largely reached locomotor
      independence. Nest-building skills were also well-developed in 3-year-olds, but
      immatures shared their mother's nest until weaned at around age 7. At time of
      birth of the new sibling, association with the mother had begun to decline for
      both male and female offspring, suggesting that the immatures had mastered all
      the necessary skills, including basic tool use, to feed themselves. By about 11
      years of age, they also ranged independently from the mother. These results show
      that orangutans do not develop independence more slowly than chimpanzees. Why,
      then, is weaning 2 years later in orangutans? In chimpanzees, mothers are often
      accompanied by two or even three consecutive offspring, unlike in orangutans.
      This contrast suggests that an orangutan mother cannot give birth until the
      previous offspring is ecologically competent enough to begin to range
      independently of her, probably due to the high energy costs of association. Thus,
      the exceptionally long interbirth intervals of orangutans may be a consequence of
      their solitary lifestyle.

PMID- 15472891
TI  - Evidence for a molecular mechanism of teratogenicity of SB-236057, a 5-HT1B
      receptor inverse agonist that alters axial formation.
AB  - BACKGROUND: SB-236057 is a potent skeletal teratogen in rodents and rabbits,
      producing axial and posterior somite malformations in cultured rat embryos. The
      compound shares some structural similarity to cyclopamine. METHODS: M13 phage
      display was used to identify amino acid motifs with binding affinity to SB
      236057. A 10 microM SB-236057 solution was administered to cultured day 9
      postcoitus rat embryos and real-time PCR was conducted at 6 hr posttreatment to
      evaluate early transcriptional response of axial development genes. Whole-mount
      in situ hybridization of selected transcripts was conducted on embryos at 48 hr
      post-compound administration. The rat-enhancer of split protein 1 (r-esp1)
      expression-functional characterization was done by transcriptional expression and
      morpholino antisense approaches. RESULTS: We identified several amino acid motifs
      that had high binding affinity to SB-236057-biotin conjugates, one with 100%
      sequence homology to a region of r-esp1, one of the Groucho homologs transcribed
      by the enhancer of split complex (En[spl]C). SB-236057 repressed expression of r
      esp1 and members of the Notch-En[spl]C pathway. Goosecoid and HNF3-beta, both
      suspected to associate with Groucho proteins, were also responsive, although
      expression of another putative binding protein, engrailed-1 (en-1), and other en
      1 pathway members was not affected. R-esp1 mRNA was localized along the axis and
      antisense inhibition produced similar somite malformations as SB-236057 did. At
      48 hr post-SB-236057 or post-r-esp1 antisense administration, affected embryos
      demonstrated unchanged sonic hedgehog (shh) expression, however HNF3-beta
      expression was either absent, altered, or reduced. CONCLUSIONS: We present
      experimental evidence that the mechanism of SB-236057 teratogenicity includes
      transcriptional alterations to the Notch1-En[spl] pathway. In addition,
      alterations in HNF3-beta expression were similar to those induced by cyclopamine.
      The relationships between r-esp1 with Notch1 and shh signaling pathways and
      potential mechanisms of SB-236057 teratogenicity are also discussed.

PMID- 15472892
TI  - Curvature, length, and cross-sectional geometry of the femur and humerus in
      anthropoid primates.
AB  - The aims of this study were to describe the curvature of anthropoid limb bones
      quantitatively, to determine how limb bone curvature scales with body mass, and
      to discuss how bone curvature influences static measures of bone strength. Femora
      and humeri in six anthropoid genera of Old World monkeys, New World monkeys, and
      gibbons were used. Bone length, curvature, and cross-sectional properties were
      incorporated into the analysis. These variables were obtained by a new method
      using three-dimensional morphological data reconstructed from consecutive CT
      images. This method revealed the patterns of curvature of anthropoid limb bones.
      Log-transformed scaling analyses of the characters revealed that bone length and
      especially bone curvature strongly reflected taxonomic/locomotor differences. As
      compared with Old World monkeys, New World monkeys and gibbons in particular have
      a proportionally long and less curved femur and humerus relative to body mass. It
      is also revealed that the section modulus relative to body mass varies less
      between taxonomic/locomotor groups in anthropoids. Calculation of theoretical
      bending strengths implied that Old World monkeys achieve near-constant bending
      strength in accordance with the tendency observed in general terrestrial mammals.
      Relatively shorter bone length and larger A-P curvature of Old World monkeys
      largely contribute to this uniformity. Bending strengths in New World monkeys and
      gibbons were, however, a little lower under lateral loading and extremely
      stronger and more variable under axial loading as compared with Old World
      monkeys, due to their relative elongated and weakly curved femora and humeri.
      These results suggest that arboreal locomotion, including quadrupedalism and
      suspension, requires functional demands quite dissimilar to those required in
      terrestrial quadrupedalism.

PMID- 15472893
TI  - Multidrug resistance-associated protein (MRP1) is overexpressed in DNA aneuploid
      carcinomatous cells in non-small cell lung cancer (NSCLC).
AB  - Resistance to chemotherapy is intrinsically present in most nonsmall-cell lung
      carcinomas (NSCLC). No parameter has yet been determined to predict the response
      to chemotherapy. However, MRP1 (multidrug resistance-associated protein) is
      suspected to play an important role in resistance to treatment. The genetic basis
      for this resistance is not clearly understood, but it could result from
      chromosome reassortments catalyzed by aneuploidy. The aim of this study was to
      investigate MRP1 expression concurrently to DNA ploidy analysis in order to
      evaluate the link between MRP1 expression and chromosome 16 (MRP1 gene location)
      aberrations in NSCLC before treatment. Eighty-four surgical tumor specimens, 18
      selected samples containing more than 80% of carcinomatous cells and 11 samples
      from normal bronchial epithelium were studied. Samples were stained by MRP1 FITC
      indirect staining and propidium iodide and analyzed by Flow Cytometry. Fifty
      tumors contained at least 1 DNA-aneuploid clone and the percentage of MRP1
      positive cells was higher in DNA-aneuploid cells (p = 0.0003). All tumors
      expressed MRP1, but the level of expression was 3-fold higher in DNA-aneuploid
      cells than in DNA-diploid cells (normal bronchial cells as well as carcinomatous
      cells) (p < 0.0001). FISH analysis of 24 tumor imprints using a chromosome 16
      alpha-satellite centromere probe demonstrated significantly more frequent gain of
      chromosome 16 in DNA-aneuploid tumors. These results suggest that MRP1
      overexpression in NSCLC could be a consequence of chromosome 16 reassortments
      catalyzed by aneuploidy and that DNA-aneuploid tumors could require different
      treatment modalities from those applied to DNA-diploid tumors.

PMID- 15472894
TI  - Human body mass estimation: a comparison of "morphometric" and "mechanical"
      methods.
AB  - In the past, body mass was reconstructed from hominin skeletal remains using both
      "mechanical" methods which rely on the support of body mass by weight-bearing
      skeletal elements, and "morphometric" methods which reconstruct body mass through
      direct assessment of body size and shape. A previous comparison of two such
      techniques, using femoral head breadth (mechanical) and stature and bi-iliac
      breadth (morphometric), indicated a good general correspondence between them
      (Ruff et al. [1997] Nature 387:173-176). However, the two techniques were never
      systematically compared across a large group of modern humans of diverse body
      form. This study incorporates skeletal measures taken from 1,173 Holocene adult
      individuals, representing diverse geographic origins, body sizes, and body
      shapes. Femoral head breadth, bi-iliac breadth (after pelvic rearticulation), and
      long bone lengths were measured on each individual. Statures were estimated from
      long bone lengths using appropriate reference samples. Body masses were
      calculated using three available femoral head breadth (FH) formulae and the
      stature/bi-iliac breadth (STBIB) formula, and compared. All methods yielded
      similar results. Correlations between FH estimates and STBIB estimates are 0.74
      0.81. Slight differences in results between the three FH estimates can be
      attributed to sampling differences in the original reference samples, and in
      particular, the body-size ranges included in those samples. There is no evidence
      for systematic differences in results due to differences in body proportions.
      Since the STBIB method was validated on other samples, and the FH methods
      produced similar estimates, this argues that either may be applied to skeletal
      remains with some confidence.

PMID- 15472895
TI  - Chromosomal imbalances detected by array comparative genomic hybridization in
      human oligodendrogliomas and mixed oligoastrocytomas.
AB  - Loss of heterozygosity and fluorescence in situ hybridization (FISH) studies have
      shown that deletions of 1p and 19q are highly prevalent in oligodendroglioma.
      However, these tumors have not been comprehensively screened for other
      alterations in chromosomal dosage. In this study, we used array-based comparative
      genomic hybridization (CGHa) of mapped BAC DNA to screen for such alterations in
      31 oligodendrogliomas (20 grade II, 9 grade III, and 2 grade IV) and 4 mixed
      oligoastrocytomas (1 grade I, 1 grade II, and 2 grade IV). The most frequent
      aberrations were loss of 1p (17 cases; 49%) and 19q (15 cases; 43%) and combined
      loss of 1p/19q (13 cases; 37%). In addition, deletion of 4q, 5p, 9p, 10q, 11p,
      and 13q was observed in 10, 4, 8, 4, 4, and 13 cases, respectively; loss of whole
      chromosomes 4, 9, and 13 in 4, 1, and 7 cases, respectively; gain of 7p, 8q, 10p,
      and 11q in 6, 6, 5, and 10 cases, respectively, and gain of whole chromosomes 7
      and 11 in 2 patients each. Minimally altered regions detected by CGHa involved
      chromosome bands 1p36.32, 4q33, 5p15, 8q24, 11p15, and 19q13.3. Univariate
      analysis of all 35 cases suggested that combined deletion of 1p and 19q is
      associated with better survival (P = 0.03). In addition, 8q gain in the
      oligodendrogliomas was strongly associated with poor outcome (P = 0.002). Also
      associated with poor disease outcome were alterations that had low prevalence in
      the pure oligodendrogliomas, including loss of 3q, 9q, and 12q and gain of 1p,
      8p, and 10q. In summary, in oligodendrogliomas, CGHa was able to detect novel
      small alterations in chromosomal dosage that had not been previously detected by
      other methods. In addition, our findings support the hypotheses that
      oligodendroglioma can be classified into several groups by CGHa analysis and that
      specific alterations in genetic dosage may have biologic or clinical
      significance.

PMID- 15472896
TI  - Genomic instability in multiple myeloma: evidence for jumping segmental
      duplications of chromosome arm 1q.
AB  - Multiple myeloma (MM) is a malignant plasma cell disorder characterized by
      complex karyotypes and chromosome 1 instability at the cytogenetic level.
      Chromosome 1 instability generally involves partial duplications, whole-arm
      translocations, or jumping translocations of 1q, identified by G-banding. To
      characterize this instability further, we performed spectral karyotyping and
      fluorescence in situ hybridization with probes for satII/III (1q12), BCL9 (1q21),
      and IL6R (1q21) on the karyotypes of 44 patients with known 1q aberrations. In
      eight patients, segmental duplication of 1q12-21 and adjacent bands occurred on
      nonhomologous chromosomes. In five cases, the 1q first jumped to a nonhomologous
      chromosome, after which the 1q12-21 segment again duplicated itself 1-3 times. In
      three other cases, segmental duplications occurred after the 1q first jumped to a
      nonhomologous chromosome, where the proximal adjacent nonhomologous chromosome
      segment was duplicated prior to the 1q jumping or inserting itself into a new
      location. These cases demonstrate that satII/III DNA sequences are not only
      associated not only with the duplication of adjacent distal chromosome segments
      after translocation, but are also associated with the duplication and
      jumping/insertion of proximal nonhomologous chromosome segments. We have
      designated this type of instability as a jumping segmental duplication.

PMID- 15472897
TI  - The MMA1 gene family of cancer-testis antigens has multiple alternative splice
      variants: characterization of their expression profile, the genomic organization,
      and transcript properties.
AB  - Previously, we reported the identification of MMA1A by screening for differential
      gene expression in two human melanoma cell lines displaying diverse metastatic
      behavior after subcutaneous inoculation into nude mice. Splice variant MMA1B,
      which also was identified through database homology searches, showed a high
      degree of similarity with the MMA1A for exons 1, 2, and 4, but was missing exon
      3. Through extensive expression profiling among normal and tumor samples, both
      MMA1A and -1B were found to belong to the family of cancer-testis antigens. In
      this study, we identified four additional alternatively spliced MMA1 variants,
      named MMA1C, MMA1D, MMA1E, and MMA1F. Generally, these novel MMA1 transcripts
      differ from MMA1A in that exon 2 or exon 3 is enlarged because of the use of
      alternative splice sites in intron 2 of the MMA1 gene. Moreover, MMA1E also lacks
      exon 3, as was previously seen in MMA1B. In screening for expression of the novel
      MMA1 transcripts in normal and tumor tissues, we demonstrated that MMA1C, -1D,
      and -1E also are members of the cancer-testis antigen family. MMA1F was found in
      only one melanoma metastasis sample and therefore is believed to have been
      expressed incidentally. Furthermore, we comprehensively elucidated the genomic
      structure of the MMA1 gene and the characteristic features of the alternatively
      spliced MMA1 transcripts.

PMID- 15472898
TI  - Fetal and infant head circumference sexual dimorphism in primates.
AB  - Studies have shown that after controlling for the effects of body size on brain
      size, the brains of adult humans, rhesus monkeys, and chimpanzees differ in
      relative size, where males have a greater volume of cerebral tissue than females.
      We assess whether head circumference sexual dimorphism is present during early
      development by evaluating sex differences in relative head circumference in
      living fetuses and infants within the first year of life. Head circumference is
      used as a proxy for brain size in the fetus and infant. Femur length is used as a
      proxy for body length in the fetus. Ultrasonography was used to obtain fetal
      measures, and anthropometry was used to obtain postnatal measures in humans,
      rhesus monkeys, baboons, and common marmosets. We show that statistically
      significant but low levels of head circumference sexual dimorphism are present in
      humans, rhesus monkeys, and baboons in early life. On average, males have head
      circumferences about 2% larger than females of comparable femur/body length in
      humans, rhesus monkeys, and baboons. No evidence for head circumference sexual
      dimorphism in the common marmoset was found. Dimorphism was present across all
      body size ranges. We suggest that head circumference sexual dimorphism emerges
      largely postnatally and increases throughout maturation, particularly in humans
      who reach adult dimorphism values greater than the monkeys. We suggest that brain
      dimorphism is not likely to impose an additional energetic burden to the
      gestating or lactating mother. Finally, some of the problems with ascribing
      functional significance to brain size sexual dimorphism are discussed, and the
      energetic implications for brain size sexual dimorphism in infancy are assessed.

PMID- 15472899
TI  - Primate hearing from a mammalian perspective.
AB  - This review discusses hearing performance in primates and selective pressures
      that may influence it. The hearing sensitivity and sound-localization abilities
      of primates, as indicated by behavioral tests, are reviewed and compared to
      hearing and sound localization among mammals in general. Primates fit the
      mammalian pattern with small species hearing higher frequencies than larger
      species in order to use spectral/intensity cues for sound localization. In this
      broader comparative context, the restricted high-frequency hearing of humans is
      not unusual. All of the primates tested so far are able to hear frequencies below
      125 Hz, placing them among the majority of mammals. Sound-localization acuity has
      been determined for only three primates, and here also they have relatively good
      localization acuity (with a minimum audible angle roughly similar to other
      mammals such as cats, pigs, and opossums). This is in keeping with the pattern
      among mammals in general, in which species with narrow fields of best vision,
      such as a fovea, are better localizers than those with broad fields of best
      vision. Multiple lines of evidence support the view that sound localization is
      the selective pressure on smaller primates and on other mammals with short
      interaural distances for hearing high frequencies.

PMID- 15472900
TI  - Apoptosis of circulating tumor cells in prostate cancer patients.
AB  - BACKGROUND: The prescence of circulating tumor cells (CTCs) in the peripheral
      blood of cancer patients and their frequency has been correlated with disease
      status. METHODS: In this study, CTCs were characterized by flow cytometry and
      fluorescence microscopy after immunomagnetic enrichment from 7.5-ml blood samples
      collected from patients with prostate cancer in evacuated blood-draw tubes that
      contained an anticoagulant and a preservative. Events were classified as tumor
      cell candidates if they expressed cytokeratin, lacked CD45, and stained with the
      nucleic acid dye 4,6-diamidino-2-phenylindole. RESULTS: In the blood of prostate
      cancer patients, only few of these events were intact cells. Other CTC events
      appeared as damaged cells or cell fragments by microscopy. By flow cytometry,
      these events stained variably with 4,6-diamidino-2-phenylindole and frequently
      expressed the apoptosis-induced, caspase-cleaved cytokeratin 18. Similar patterns
      of cell disintegration were observed when cells of the prostate line LNCaP were
      exposed to paclitaxel before spiking the cells into normal blood samples.
      CONCLUSIONS: The different observed stages of tumor cell degradation or apoptosis
      varied greatly between patients and were not found in blood of normal donors.
      Enumeration of CTCs and identification of CTCs undergoing apoptosis may provide
      relevant information to evaluate the response to therapy in cancer patients.

PMID- 15472901
TI  - Influence of calcium ions in the flow cytometric analysis of human CD8-positive
      cells.
AB  - BACKGROUND: The CD8 co-receptor is an important marker used to identify various
      lymphocyte subsets. A significant decrease in CD8alpha staining intensity was
      observed in the presence of divalent cation chelators. METHODS: Peripheral blood
      mononuclear cells (PBMC) obtained from healthy volunteers were treated with
      calcium chelators, stained with different anti-human CD8 mAbs, and analyzed by
      flow cytometry. RESULTS: Calcium chelators caused a dose-dependent decrease in
      fluorescence intensity, using specific anti-human CD8alpha mAbs. This phenomenon
      was not due to CD8 internalization and could be reversed by the addition of
      calcium ions. In contrast, calcium depletion increased staining intensity with
      one anti-CD8beta mAb. CONCLUSIONS: Divalent cation chelators are used as cell
      anti-clumping agents in MACS or FACS applications. Researchers should be aware
      that such treatment could lead to the almost complete loss of fluorescence with
      selected anti-human CD8alpha mAbs. Since CD8 staining is used in conjunction with
      tetramer staining to identify antigen-specific cytotoxic human T cells, the
      effect of calcium depletion should be taken into account in experimental design.

PMID- 15472902
TI  - Distribution of olfactory epithelium in the primate nasal cavity: are microsmia
      and macrosmia valid morphological concepts?
AB  - The terms "microsmatic" and "macrosmatic" are used to compare species with
      greater versus lesser olfactory capabilities, such as carnivores compared to
      certain primates. These categories have been morphologically defined based on the
      size of olfactory bulb and surface area of olfactory epithelium in the nasal
      fossa. The present study examines assumptions regarding the morphological
      relationship of bony elements to the olfactory mucosa, the utility of olfactory
      epithelial surface area as a comparative measurement, and the utility of the
      microsmatic concept. We examined the distribution of olfactory neuroepithelium
      (OE) across the anteroposterior length of the nasal fossa (from the first
      completely enclosed cross-section of the nasal fossa to the choanae) in the
      microsmatic marmoset (Callithrix jacchus) compared to four species of nocturnal
      strepsirrhines (Otolemur crassicaudatus, O. garnetti, Microcebus murinus, and
      Cheirogaleus medius). Adults of all species were examined and infant C. jacchus,
      O. crassicaudatus, M. murinus, and C. medius were also examined. All specimens
      were serially sectioned in the coronal plane and prepared for light microscopic
      study. Distribution of OE across all the turbinals, nasal septal surfaces, and
      accessory spaces of the nasal chamber was recorded for each specimen. The right
      nasal fossae of one adult C. jacchus and one neonatal M. murinus were also three
      dimensionally reconstructed using Scion Image software to reveal OE distribution.
      Findings showed OE to be distributed relatively more anteriorly in adult C.
      jacchus compared to strepsirrhines. It was also distributed more anteriorly along
      the nasal septal walls and recesses in neonates than adults. Our findings also
      showed that OE surface area was not a reliable proxy for receptor neuron numbers
      due to differing OE thickness among species. Such results indicate that nasal
      cavity morphology must be carefully reconsidered regarding traditional functional
      roles (olfaction versus air conditioning) assigned to various nasal cavity
      structures. At present, the microsmatic concept itself lacks a basis in nasal
      chamber morphology, since OE may have varying patterns of distribution among
      different primates.

PMID- 15472903
TI  - Expression patterns of potential therapeutic targets in prostate cancer.
AB  - Androgen withdrawal is the only effective therapy for patients with advanced
      prostate cancer, but progression to androgen independence ultimately occurs in
      almost all patients. Novel therapeutic strategies targeting molecular mechanisms
      that mediate resistance to hormonal and chemotherapeutic treatment are highly
      warranted. Here, we aimed to evaluate the expression of potential therapeutic
      targets in advanced prostate cancer. A tissue microarray (TMA) containing samples
      from 535 tissue blocks was constructed, including benign prostatic hyperplasia as
      controls (n = 65), prostatic intraepithelial neoplasia (PIN; n = 78), clinically
      localized prostate cancers (n = 181), as well as hormone-refractory local
      recurrences (n = 120) and distant metastases (n = 91). The expression of 13
      different proteins was analyzed using immunohistochemistry (Bcl-2, p53, ILK,
      Syndecan-1, MUC-1, EGFR, HER2/neu, HSP-90, Ep-CAM, MMP-2, CD-10, CD-117 and
      Ki67). Significant overexpression in hormone-refractory prostate cancer and
      metastatic tissue compared to localized prostate cancer was found for Ki67 (64%
      vs. 9%), Bcl-2 (11% vs. 1%), p53 (35% vs. 4%), Syndecan-1 (38% vs. 3%), EGFR (16%
      vs. 1%) and HER2/neu (16% vs. 0%). Overexpression of CD-117 was restricted to 1
      single metastasis. All other markers did not show relevant differences in
      expression between subgroups. Taken together, p53, Bcl-2, Syndecan-1, EGFR and
      HER2/neu are preferentially expressed in hormone-refractory and metastatic
      prostate cancer. Selected inhibition of these targets might offer a strategy to
      treat advanced tumors and prevent further progression. Treatment decisions should
      not be based on findings in primary tumors but rather on tissues from recurrent
      or metastatic lesions.

PMID- 15472904
TI  - Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor
      characteristics among unselected breast cancer patients.
AB  - The CHEK2 kinase is a tumor suppressor whose activation in response to DNA double
      strand breaks contributes to cell cycle arrest or apoptosis. The c.1100delC
      mutation is associated with familial breast cancer, and tumors from mutation
      carriers show reduced or absent CHEK2 protein expression. We have here studied
      CHEK2 protein expression by immunohistochemistry on a tissue microarray of 611
      unselected breast tumors and also evaluated the tumor characteristics among 1,297
      unselected breast cancer patients defined for the c.1100delC germ line mutation
      status (2.5% carrier frequency). CHEK2 protein expression was reduced in 21.1% of
      the unselected breast cancers studied. Tumors with reduced CHEK2 expression had
      more often larger primary tumor size (pT3-4; nominal significance p = 0.002)
      compared to tumors with normal staining. A similar trend for larger tumor size
      was seen among the 37 breast tumors from c.1100delC germ line mutation carriers.
      Tumors from c.1100delC mutation carriers were of higher grade than those of
      noncarriers (nominal significance p = 0.02). The c.1100delC germ line mutation
      also associated strongly with bilateral breast cancer. No significant correlation
      was seen between CHEK2 status and hormone receptor status, histology, lymph node
      status, or overall survival.

PMID- 15472905
TI  - Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice.
AB  - A prominent phenotype of plasmin deficiency in mice is reduced metastasis in the
      MMTV-PymT transgenic breast cancer model. Proteolytically active plasmin is
      generated from inactive plasminogen by one of 2 activators, uPA or tPA. We now
      find that uPA deficiency alone significantly reduces metastasis >7-fold in the
      MMTV-PymT model. We studied a cohort of 55 MMTV-PymT transgenic mice, either uPA
      deficient or wild-type controls. Tumor incidence, latency, growth rate and final
      primary tumor burden were not significantly affected by uPA deficiency. In
      contrast, average lung metastasis volume was reduced from 1.58 mm(3) in wild-type
      controls to 0.21 mm(3) in uPA-deficient mice (p = 0.023). Tumor cell
      dissemination to brachial lymph nodes was also reduced from 53% (28/53) in wild
      type controls to 31% (17/54) in uPA-deficient mice (p = 0.032). Mice without
      plasminogen display a severe pleiotropic phenotype. By comparison, spontaneous
      phenotypes are modest in uPA-deficient mice, probably because they still have
      active tPA. We show that metastasis is strongly and selectively decreased in uPA
      deficient mice, suggesting that uPA-directed antimetastatic therapy would be
      efficacious and have limited side effects.

PMID- 15472906
TI  - Anti-angiogenic therapy subsequent to adeno-associated-virus-mediated
      immunotherapy eradicates lymphomas that disseminate to the liver.
AB  - Liver cancer has a very poor prognosis and lacks effective therapy. We have
      previously demonstrated that intraportal injection of adeno-associated-viral
      (AAV) particles that express angiostatin lead to long-term expression of
      angiostatin capable of suppressing the outgrowth of EL-4 tumors in the liver.
      Here we combine AAV-mediated angiostatin therapy with immunotherapy by employing
      an AAV vector encoding the T-cell costimulator B7.1. Incubation of EL-4 cells
      with AAV-B7.1 viruses resulted in the rapid expression of B7.1 on the surface of
      80% of EL-4 cells. Mice that were vaccinated with B7.1-engineered tumor cells
      rejected the tumor cells and resisted a secondary challenge with unmodified
      parental cells. Splenocytes from the vaccinated mice were highly cytotoxic
      towards parental EL-4 cells in vitro. However, the vaccinated mice failed to
      resist the challenge of a heavy burden of EL-4 cells. Intraportal injection of
      AAV particles that express angiostatin into mice that had been vaccinated 1 month
      earlier with B7.1-engineered tumor cells protected mice against the challenge of
      a heavy burden of EL-4 cells and eradicated tumors that had disseminated to the
      liver. The combinational therapy increased the survival rate of mice with
      advanced liver cancer. These encouraging results warrant investigation of the
      employment of anti-angiogenic therapy subsequent to cancer immunotherapy for
      targeting unresectable disseminated liver metastases.

PMID- 15472907
TI  - Wnt/beta-catenin-pathway as a molecular target for future anti-cancer
      therapeutics.
AB  - Conventional chemotherapeutic drugs used for the treatment of cancer patients in
      advanced stages have yielded only limited benefit, regarding survival time not to
      mention cure of the patients. To improve the clinical outcome of cancer, agents
      aimed at novel molecular targets are required. Colorectal and many other cancers
      are caused by hyperactivity of the Wnt/beta-catenin signaling pathway that
      results in constitutive beta-catenin mediated transactivation of T cell factor
      (Tcf)-dependent genes. Accordingly, disruption of this signaling pathway holds
      promise for the development of new anti-cancer drugs. Our study describes recent
      therapeutic strategies to interfere with tumor growth by blocking the
      unrestricted activation of the Wnt/beta-catenin pathway. The antagonists, which
      may become lead compounds of new anticancer therapeutics include established
      drugs in new application areas, recombinant biomolecules, virus mediated
      selective cell killing, and small molecules, disrupting protein-protein
      interactions.

PMID- 15472908
TI  - Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many
      human malignancies.
AB  - HIN-1 (high in normal-1) is a putative cytokine with growth inhibitory activities
      and is downregulated by aberrant methylation in breast cancers. We studied HIN-1
      methylation status in many types of adult and pediatric malignancies and cell
      lines. We examined the expression of HIN-1 mRNA in 52 cell lines and the promoter
      methylation status in the cell lines and in over 800 primary tumors representing
      17 tumor types using methylation specific PCR. Promoter methylation was observed
      in 73% of breast cancer, 67% of nonsmall cell lung cancer (NSCLC), 30% of small
      cell lung cancer (SCLC) and 57% of malignant mesothelioma (MM) cell lines, and
      methylation was completely correlated with loss of expression. Expression
      negative cell lines restored HIN-1 expression after treatment with 5-aza-2'
      deoxycytidine. Promoter methylation of HIN-1 was found in 90% of retinoblastomas,
      73% of Wilms' tumors, 61% of rhabdomyosarcomas, 57% of breast cancers, 52% of
      prostate cancers, 40% of MMs, 28% of NSCLCs and 27% of lymphomas. Methylation
      frequencies in colorectal cancers, cervical cancers, bronchial carcinoids, SCLCs,
      neuroblastomas, osteosarcomas, leukemia, medulloblastomas and bladder cancers
      were lower (4-21%), while hepatoblastomas lacked methylation. HIN-1 methylation
      was rarely detected in nonmalignant tissues (8 of 165, 5%). Aberrant methylation
      of HIN-1 with loss of expression is a common event and may contribute to the
      pathogenesis of many types of human malignancies.

PMID- 15472909
TI  - Selective inhibition of cyclooxygenase (COX)-2 inhibits endothelial cell
      proliferation by induction of cell cycle arrest.
AB  - High-level expression of cyclooxygenase (COX)-2 is reported in 80-90% of
      colorectal adenocarcinomas. Selective inhibition of COX-2 was shown to reduce
      colorectal tumorigenesis in different models of carcinogenesis and to prevent
      metastasis in xenograft tumor models, as well as to suppress in vitro induced
      angiogenesis. Recently, COX-2 was reported to be expressed not only in malignant
      epithelial cells, but also in the neovasculature that feeds the tumor in a
      variety of solid human cancers. Thus, one of the possible mechanisms by which
      selective COX-2 inhibitor reduces tumor growth and metastasis is through
      inhibition of tumor angiogenesis. Although a report suggested a possible role of
      endothelial COX-1 in the process of angiogenesis, in a recent study, the
      selective inhibition of COX-2 was shown to strongly inhibit angiogenesis by
      inducing endothelial cell (EC) apoptosis. In the present study, using human
      umbilical vein endothelial cells (HUVECs) as a model of angiogenesis, we
      investigated the potential antiangiogenic effect of the selective COX-2 inhibitor
      and its mechanism of action, and clearly demonstrated that selective inhibition
      of COX-2 caused a dose-dependent decrease in the proliferative activity of ECs,
      as well as an inhibition of capillary-like tube formation. The inhibitory effect
      on EC proliferation was dependent on the cell cycle arrest to the G1 phase and
      not on cell apoptosis.

PMID- 15472910
TI  - Treatment of AIDS-associated Kaposi's sarcoma in Zimbabwe: results of a
      randomized quality of life focused clinical trial.
AB  - Kaposi's sarcoma is currently the most common tumor in Zimbabwe. The purpose of
      our study is to compare the effectiveness of supportive care vs. 3 intervention
      approaches, namely oral Etoposide, a 3-drug combination, and radiotherapy using
      quality of life (QOL) as the primary measure of success. In addition, our study
      was to determine whether a disease-specific module has greater sensitivity to
      group differences than a generic QOL questionnaire and to determine the most
      pragmatic approach to treating epidemic Kaposi's sarcoma (EKS) in Zimbabwe.
      Histologically confirmed HIV-positive patients with Kaposi's sarcoma were
      randomized to receive supportive care only or supportive care plus either
      radiotherapy, oral Etoposide or a 3-drug combination consisting of actinomycin-D,
      vincristine and bleomycin. No patient received antiretroviral therapy. The
      primary outcome was QOL measured by the functional living index-cancer (FLI-C)
      and supplemented by the Kaposi's sarcoma module (KSM). From 1994-1999, 495 EKS
      patients were accrued, and 470 were evaluable. Of these, 433 are known to be
      dead, 26 are lost to follow-up and 11 are still alive. The group treated with
      oral Etoposide had a significantly better QOL than the radiotherapy group for the
      total FLI-C score (adjusted mean plus standard error at 3-months 89 +/- 3 vs. 76
      +/- 3; p = 0.004) and for the hardship (11 +/- 0.4 vs. 9 +/- 0.4; p = 0.001);
      social (10 +/- 0.4 vs. 8 +/- 0.4; p = 0.001) and nausea (9 +/- 0.4 vs. 8 +/- 0.4;
      p = 0.002) subscales. In addition, on the physical and psychological subscales,
      the Etoposide group had a significantly better QOL than the other 3 treatment
      groups (p < 0.04). The 3-drug combination, supportive care and radiotherapy
      groups did not differ significantly from each other with respect to the total FLI
      C score or its subscales. There were no group differences with respect to
      survival. Oral Etoposide therapy resulted in better total FLI-C QOL score than
      radiotherapy. As well, Etoposide resulted in better physical and psychological
      subscale scores than radiotherapy, 3-drugs and supportive care. Thus, funds
      permitting, oral Etoposide is a pragmatic approach to treating EKS in an
      environment where antiretroviral drugs are not universally available. The study
      underscores the value of undertaking studies in areas of disease prevalence and
      the necessity of selecting appropriate outcome measures.

PMID- 15472913
TI  - Crystal and magnetic structure of the system Li0.5+0.5xFe2.5-1.5xTixO4 (x=0.16,
      0.44, and 0.72).
AB  - The influence of thermal treatment on the structure of lithium titanium ferrite
      spinels of general formula Li(0.5+0.5x)Fe(2.5-1.5x)Ti(x)O4 (x=0.16, 0.44, and
      0.72) has been studied by X-ray and neutron diffraction and analysed by the
      Rietveld method. The results allow us to conclude the presence of an ordered
      phase (space group P4(3)32) at room temperature for the sample with x=0.16; this
      phase does not appear for the remaining compositions. The magnetic properties
      evidence a ferrimagnetic ordering in the structures when a random cation
      distribution (space group Fd3 m) is obtained. An exhaustive study carried out by
      neutron diffraction measurements on these samples shows a different behaviour
      when the titanium content is increased, concluding that the lower substituted
      phase (x=0.16) exhibits a Neel's collinear ferrimagnetic structure, with the
      higher substituted structures being noncollinear (x=0.44 and 0.72).

PMID- 15472914
TI  - Diphosphines with expandable bite angles: highly active ethylene dimerisation
      catalysts based on upper rim, distally diphosphinated calix[4]arenes.
AB  - The binding properties of two large diphosphines, cone-5,17-dibromo-11,23
      bis(diphenylphosphino)-25,26,27,28-tetrapropoxycalix[4]arene (1) and cone-5,17
      bis(diphenylphosphino)-25,26,27,28-tetrapropoxycalix[4]arene (2) toward Ni(II)
      centres have been investigated. Whatever the starting complex, NiBr2 or
      [NiCp]BF4, quantitative formation of a chelate complex was observed, illustrating
      the preorganisation of the ligands. An X-ray structure determination was carried
      out for [NiCp1]BF4 which revealed that the nickel atom is positioned to one side
      of the calixarene axis, the PNiP plane being roughly parallel to the calixarene
      reference plane. The molecule has C(1) symmetry in the solid state, a feature
      which is also observed in solution at low temperature. As shown by variable
      temperature 1H and 31P NMR studies, the complex undergoes two distinct motions:
      1) a fan-like swinging of the coordination plane which displaces the metal from
      one side of the calixarene axis to the other, a motion during which the PNiP
      angle is likely to undergo a significant enlargement; 2) a rapid oscillation of
      each PPh2 unit about the corresponding Ni--P bond. In the latter dynamics the two
      endo-oriented PPh rings alternately occupy the calixarene entry. The two flexible
      ligands were assessed in ethylene oligomerisation. Activation with
      methylaluminoxane of the paramagnetic complexes [NiBr2.(1 or 2)] afforded highly
      active ethylene dimerisation catalysts, with turnover frequencies up to 10(6)
      (mol C2H4) (mol Ni)(-1) h(-1). The selective formation of 1-butene can be
      rationally controlled by using low catalyst concentrations.

PMID- 15472917
TI  - Hierarchical zeolites: a proven strategy to combine shape selectivity with
      efficient mass transport.

PMID- 15472918
TI  - Antiallergic activity of a disaccharide isolated from Sanguisorba officinalis.
AB  - The antiallergic activity of the natural disaccharide, 5-O-alpha-D-(3-C
      hydroxymethyl)lyxofuranosyl-beta-D-(2-C-hydroxymethyl)arabinofuranose was
      evaluated using both in vivo and in vitro experimental models. Intravenously
      administered compound inhibited the passive cutaneous anaphylaxis response in
      rats in a dose-dependent manner (ED(50) = 9.6 mg/kg). The compound inhibited
      histamine release evoked by both compound 48/80 and calcium ionophore A23187 in
      rat peritoneal mast cells indicating that mast cell stabilization is the major
      mechanism of action for its antiallergic activity. In passively sensitized
      isolated guinea-pig hearts, an in vitro anaphylaxis model in which histamine
      release plays a key role for functional deterioration, the compound markedly
      diminished both coronary flow reduction and histamine release on challenge to the
      antigen. These data demonstrate that this antiallergic natural disaccharide
      exerts its effect via inhibition of mast cell mediator release.

PMID- 15472919
TI  - Neuroprotective effect of Ginkgo biloba L. extract in a rat model of Parkinson's
      disease.
AB  - The neuroprotective effects of a standardized extract of Ginkgo biloba L. (EGb
      761) were investigated on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in the
      nigrostriatal dopaminergic system of the rat brain. Rats were given a week of
      pretreatment with daily administrations of EGb 761. Unilateral striatal injection
      of 6-OHDA was followed by treatment with EGb 761 for a week. Serial measurement
      of contralateral forepaw adjusting steps revealed a progressive deficit in motor
      activity. At 8 weeks after 6-OHDA lesion the number of contralateral forepaw
      adjusting steps was significantly higher in rats that were treated with high
      doses of EGb 761 (100 mg/kg daily) than in those treated with low doses (50
      mg/kg) or with the vehicle. Dopamine neuron loss in the substantia nigra and a
      depletion in striatal dopamine corresponded with behavioural deficit. These data
      suggest that the neuroprotective effects of EGb 761 reduce the behavioural
      deficit in 6-OHDA lesions in rat and also indicates a possible role for the
      extract in the treatment of Parkinson's disease.

PMID- 15472920
TI  - Two ellagitannins from the leaves of Terminalia triflora with inhibitory activity
      on HIV-1 reverse transcriptase.
AB  - The bioassay- guided fractionation of the aqueous extract of Terminalia triflora
      leaves afforded punicalin and 2-O-galloylpunicalin, isolated for the first time
      from this species. These compounds showed inhibitory activity on HIV-1 reverse
      transcriptase in a dose-dependent manner. Punicalin showed an IC(50) of 0.11
      microg/ml (0.14 microM) and 2-O-galloylpunicalin an IC(50) of 0.10 microg/ml
      (0.11 microM).

PMID- 15472921
TI  - SB-236057: Critical window of sensitivity study and embryopathy of a potent
      musculoskeletal teratogen.
AB  - BACKGROUND: SB-236057 is a potent skeletal teratogen in rodents and rabbits. The
      study objective was to identify the critical developmental window of compound
      sensitivity and to characterize the early onset of SB-236057 embryopathy.
      METHODS: SB-236057 was orally administered to Sprague Dawley dams at 100
      mg/kg/day on days 6-7, 8-11, 12-14, or 15-17 postcoitus (pc). The critical window
      of sensitivity was identified to occur between days 8-11 pc. Dams were then dosed
      on days 8-11 pc and embryos were evaluated by histochemical procedures on days
      11, 13, or 15 pc. RESULTS: Axial malformations were evident by day 11 pc.
      Analysis of the cartilaginous skeleton revealed missing posterior axial skeletal
      elements. However, only about one-third of the malformed fetuses exhibited
      obvious rib and vertebrae abnormalities, and none of the affected fetuses
      exhibited abnormal appendicular skeletal elements. Expression pattern of sonic
      hedgehog in the notochord and floor plate was not affected, suggesting ventral
      midline signaling was not disrupted. Histological analysis demonstrated
      hypoplastic and/or missing musculature in proximity to the ribs and vertebrae.
      Caspase 3 analysis revealed no increases in apoptotic cells in the musculature.
      Confocal analysis of the limbs demonstrated truncated peripheral nerve formation
      and shortening of the appendicular musculature. CONCLUSIONS: SB-236057 is
      speculated to alter paraxial mesoderm programming. Many of the skeletal
      malformations may be caused secondarily from musculature abnormalities,
      suggesting that the myotome may be particularly sensitive to the compound.
      Furthermore, the finding that peripheral nerve trajectories were altered along
      the axis and in the limb suggests that SB-236057 may alter early embryonic
      signaling pathways necessary for neuronal differentiation/axonal guidance that
      occur subsequently in embryo-fetal development.

PMID- 15472922
TI  - Cytokine secretion from mononuclear cells cultured in vitro with starch-based
      polymers and poly-L-lactide.
AB  - The cytokine network is one of the major controlling systems of the inflammatory
      process, driving the magnitude and duration of the host response against invading
      microorganisms, foreign materials, or altered internal stimuli. Pro- and
      antiinflammatory cytokines were quantified after in vitro culture of a mixed
      population of monocytes/macrophages and lymphocytes with biodegradable polymers.
      Different blends of starch-based polymers and their composites filled with
      hydroxyapatite were studied and compared with poly-L-lactide. Interleukin (IL)
      1beta, IL-6, and tumour necrosis factor-alpha were investigated as the markers of
      immunological reactivity because they are known to act at the early stages of
      injury/invasion. Interferon-gamma, recognized as a proinflammatory cytokine,
      although not present during early responses was also investigated. Contrarily, IL
      4 derived from T lymphocytes, was investigated because it is an immunoregulator
      that counteracts some aspects of inflammation. T lymphocyte activation was also
      determined by quantifying IL-2. The results support the hypothesis that different
      biodegradable polymers can affect mononuclear cell activation and the production
      of several cytokines associated with the inflammatory process. No IL-2 or
      interferon-gamma was found in the culture supernatants after 3, 7, and 14 days in
      the presence of any of the materials. IL-6 was detected in the highest amounts,
      for all the conditions, followed by tumour necrosis factor-alpha. IL-1beta was
      produced in very low amounts, being undetectable with some of the starch-based
      materials. IL-4 was the only cytokine that did not demonstrate any significant
      difference within this group of materials. Starch-based polymers and composites
      induced lower production of proinflammatory cytokines in comparison to poly-L
      lactide.

PMID- 15472923
TI  - Enamel thickness of deciduous and permanent molars in modern Homo sapiens.
AB  - This study presents data on the enamel thickness of deciduous (dm2) and permanent
      (M1-M3) molars for a geographically diverse sample of modern humans. Measurements
      were recorded from sections through the mesial cusps of unworn teeth. Enamel is
      significantly thinner on deciduous than on permanent molars, and there is a
      distinct trend for enamel to increase in relative thickness from M1 to M3. The
      relatively thicker enamel of M2s and especially M3s can be related to the overall
      reduction in size of more distal molar crowns, which has been attained through a
      differential loss of the dentine component. Enamel tends to be thicker on the
      protocone than on the paracone, and thicker on the protoconid than on the
      metaconid, but its distribution is not wholly concordant with models that predict
      increased thickness as a means by which to counter heavier attritional loss on
      these "functional" cusps. Indeed, the thickness of enamel tends to be more
      variable on cusp tips and occlusal surfaces than over the lateral aspects of
      cusps. The proportionately thicker enamel over the lateral aspects of the
      protocone and protoconid more likely serves as a means to prolong functional
      crown life by preventing cusp fracture, rather than being an adaptation to
      increase the attritional longevity of wear facets. The present data suggest that
      the human dentition is not predisposed to develop a helicoidal wear plane through
      the disposition of molar enamel thickness.

PMID- 15472924
TI  - Ectopic bone formation using osteogenic protein-1 carried by a solution
      precipitated hydroxyapatite.
AB  - Solution precipitation of calcium and phosphate is a technique to generate
      hydroxyapatite [Peri-Apatitetrade mark (PA), Stryker Orthopaedics, Mahwah, NJ] on
      metal substrate. This study was carried out to determine the capacity of PA to
      adsorb osteogenic protein-1 (OP-1) and the time course of release, and to
      determine the osteoinductive activity of OP-1. The adsorption and release studies
      were conducted with (125)I-labeled OP-1- and PA-coated titanium alloy disks. The
      results indicate that the adsorption of OP-1 on the PA-coated disks is linear
      with the concentration of OP-1 up to 5 mg/mL. There is an initial release of 75%
      to 80% of adsorbed OP-1 within the first hour, and 92% of OP-1 is released in 3
      days. The osteoinductive activity of OP-1 was determined in the rat intramuscular
      ectopic bone formation assay. A total of 24 titanium alloy disks were evenly
      divided into 3 groups with different treatments for implantation, plain disks
      (group A), disks coated with PA (group B), and disks coated with PA plus 40
      microg OP-1 (group C). Osteogenic protein-1, 40 microg in solution, was injected
      into the muscle pouch in animals of group D (n = 8). The rats were sacrificed 3
      weeks postoperatively and the implants were retrieved. Ectopic bone formation was
      evaluated with radiography and histology. Results demonstrated that OP-1 induced
      ectopic bone in all the animals of group C and group D. The titanium alloy disks
      were surrounded by trabecular bone and marrow tissue. None of the animals of
      group A or group B showed any evidence of osteoinduction. Our findings indicate
      that PA can deliver OP-1 directly to titanium alloy implants and maintain the
      osteoinductive activity of OP-1.

PMID- 15472925
TI  - Unexpected distribution of immobilized microorganisms within alginate beads.
AB  - Immobilization refers to the prevention of free cell movement by natural or
      artificial means. It has always been assumed that immediately after an
      immobilization procedure is performed, cells are distributed homogeneously in the
      beads that entrap them. However, in this study, Escherichia coli and Trichoderma
      asperellum distribution in alginate-gel beads was found to be nonhomogeneous. In
      fact, there was a greater presence of cells on the surface of the alginate beads
      than in their cores.

PMID- 15472926
TI  - Analysis of streptonigrin-induced incomplete chromosome elements and interstitial
      fragments in Chinese hamster cells using a telomeric PNA probe.
AB  - We investigated the induction of incomplete chromosome elements (ICEs; i.e.,
      elements with a telomeric signal at only one terminal end) and interstitial
      fragments induced by the antibiotic streptonigrin (SN) in a Chinese hamster
      embryo (CHE) cell line using FISH with a telomeric peptide nucleic acid probe.
      CHE cells were treated with 0-250 ng/ml SN and chromosomal aberrations were
      analyzed in the first mitosis after treatment using the telomeric probe. Exposure
      of CHE cells to SN resulted in a linear concentration-related increase in all of
      the aberration types analyzed (P < 0.05) except ring chromosomes. Depending on
      the SN concentration employed, 33-68% of the metaphases contained one or more
      pairs of ICEs (an incomplete chromosome accompanied by a terminal fragment or two
      incomplete chromosomes accompanied by a compound fragment). Pooled data from all
      SN concentrations revealed that 77.8% of the acentric fragments were terminal
      fragments, 18.8% interstitial fragments, and 3.4% compound fragments.
      Furthermore, it was estimated that about 80% of excess acentric fragments induced
      by SN originated from incomplete exchanges or terminal deletions and 20% from
      complete exchanges (interstitial deletions). These results show that incomplete
      chromosomes and terminal fragments are the most frequent asymmetrical chromosomal
      aberrations induced by SN and indicate that true incompleteness is a very common
      event following exposure to SN.

PMID- 15472927
TI  - Highly efficient baculovirus-mediated gene transfer into rat chondrocytes.
AB  - To explore the potential of baculovirus serving as a gene delivery vector in
      tissue engineering of articular cartilage, the efficiencies of baculovirus
      mediated gene delivery into primary rat chondrocytes were evaluated and the
      transduction protocol commonly employed by others (using concentrated virus at
      multiplicity of infection [MOI] 200 for 1 h) was found to be ineffective (<1%).
      Therefore, a modified protocol was adopted, which markedly enhanced the
      efficiency (68%). Optimization of the transduction parameters, such as incubation
      time (8 h), temperature (25 degrees C), and surrounding solutions (PBS), further
      increased the efficiency to 88% and prolonged the duration of expression to 21
      days, suggesting that the cells previously considered nonpermissive to
      baculovirus transduction may be reexamined for their permissiveness using
      alternative transduction protocols. The elevated efficiency correlated well with
      increased virus uptake upon extended incubation time, as demonstrated by
      quantitative real-time polymerase chain reaction (Q-PCR). The Q-PCR also revealed
      the degradation of viral DNA over culture time. Although the virus transduction
      somewhat hindered the cell proliferation, growth rate could be restored in the
      long-term culture. More importantly, transduced cells could secrete articular
      cartilage-specific type II collagen and glycosaminoglycan as well as mock
      transduced cells, confirming that normal differentiation state of rat
      chondrocytes is retained upon baculovirus transduction. Taken together, these
      data indicate that baculovirus is a safe and highly efficient gene delivery
      vehicle into rat chondrocytes.

PMID- 15472928
TI  - Glucose metabolism in the antibiotic producing actinomycete Nonomuraea sp. ATCC
      39727.
AB  - The actinomycete Nonomuraea sp. ATCC 39727, producer of the glycopeptide A40926
      that is used as precursor for the novel antibiotic dalbavancin, has an unusual
      carbon metabolism. Glucose is primarily metabolized via the Entner-Doudoroff (ED)
      pathway, although the energetically more favorable Embden-Meyerhof-Parnas (EMP)
      pathway is present in this organism. Moreover, Nonomuraea utilizes a PPi
      dependent phosphofructokinase, an enzyme that has been connected with anaerobic
      metabolism in eukaryotes and higher plants, but recently has been recognized in
      several actinomycetes. In order to study its primary carbon metabolism in further
      detail, Nonomuraea was cultivated with [1-13C] glucose as the only carbon source
      and the 13C-labeling patterns of proteinogenic amino acids were determined by GC
      MS analysis. Through this method, the fluxes in the central carbon metabolism
      during balanced growth were estimated. Moreover, a shift in the label
      incorporation pattern was observed in connection with phosphate limitation and
      increased antibiotic productivity in Nonomuraea. The shift indicated an increased
      flux through the EMP pathway at the expense of the flux through the ED pathway, a
      suggestion that was supported by alterations in intracellular metabolite levels
      during phosphate limitation. In contrast, expression levels of genes encoding
      enzymes in the ED and EMP pathways were not affected by phosphate limitation.

PMID- 15472929
TI  - Unilateral ischemic sensorimotor cortical damage induces contralesional
      synaptogenesis and enhances skilled reaching with the ipsilateral forelimb in
      adult male rats.
AB  - Unilateral damage to the forelimb representation area of the sensorimotor cortex
      (SMC) results in a compensatory reliance on the unimpaired (ipsilateral to the
      lesion) forelimb as well as reorganization of neuronal structure and connectivity
      in the contralateral motor cortex. Recently, male rats with unilateral
      electrolytic SMC lesions were found to have enhanced skilled reaching performance
      with the ipsilesional forelimb compared with sham-operated controls. The present
      study was performed to determine whether these behavioral findings are replicable
      using an ischemic lesion and whether there is a link between the enhanced
      learning and synaptogenesis in motor cortical layer V opposite the trained limb
      and lesion, as assessed using stereological methods for light and electron
      microscopy. Rats were given a sham operation or an endothelin-1 (ET-1) induced
      ischemic SMC lesion. They were then trained for 20 days on a skilled reaching
      task with the unimpaired limb or received control procedures. As with previous
      findings using electrolytic lesions, rats with unilateral ischemic SMC lesions
      performed significantly better using the unimpaired forelimb than did sham
      operates. Lesions, but not training, significantly increased the total number of
      motor cortical layer V synapses per neuron as well as the number of perforated
      and multisynaptic bouton (MSB) synapses per neuron compared with shams. Thus, in
      addition to a net increase in synapses, the improved reaching ability was coupled
      with an increase in synapse subtypes that have previously been linked to enhanced
      synaptic efficacy. The failure to induce synaptogenesis in layer V with reach
      training alone is in contrast to previous findings and may be related to training
      intensity.

PMID- 15472930
TI  - Alteration of hippocampal cell proliferation in mice lacking the beta 2 subunit
      of the neuronal nicotinic acetylcholine receptor.
AB  - Adult hippocampal neurogenesis declines with age in parallel with decreased
      performance on a variety of hippocampal-dependent tasks. We measured the rate of
      cellular proliferation in the hippocampus of mice lacking the beta 2-subunit of
      the nicotinic acetylcholine receptor (beta 2-/- mice) at three ages: young adult
      (3 months old), fully adult (7-10 months old), and aged (22-24 months old).
      Consistent with previous studies, we observed an age-related decline in
      hippocampal proliferation in both groups. However, in fully adult beta 2-/- mice
      a 43% reduction of granule cell proliferation was detected compared to age
      matched controls. This was accompanied by a significant decrease in dentate gyrus
      area/section and the length of the granule cell layer in beta 2-/- mice. These
      alterations were not the result of a change in plasma corticosterone levels or
      expression of the neurotrophic factor BDNF in the dentate gyrus, two known
      regulators of hippocampal cell proliferation. Similarly, there was no increase in
      gliosis, abnormal myelination, or apoptotic cell death in the beta 2-/- animals,
      although there was a significant shift in the location of apoptotic cells in the
      dentate gyrus indicative of a change in neuronal survival. These results suggest
      that the beta 2-subunit containing nicotinic acetylcholine receptors play an
      important role in regulating cell proliferation in the hippocampus and that
      endogenous acetylcholine may act to oppose the negative effects of normal aging
      and stress on cellular proliferation.

PMID- 15472931
TI  - Injecting electronic excitation energy into an artificial antenna system through
      an Ru2+ complex.
AB  - The Ru2+ complex [Ru(bpy)2(bpy-ph4-Si(CH3)3)]2+ can be electrostatically bound to
      the negatively charged channel entrances of dye-loaded zeolite L crystals where
      it acts as a functional stopcock molecule. Impressive electronic triplet-singlet
      excitation energy transfer from the Ru2+ complex to the acceptor dye oxazine 1
      (Ox1) located inside the channels can be observed when the donor molecule is
      selectively excited. Time-resolved luminescence experiments have been performed
      on the separate components and on the assembled donor-acceptor material. The
      luminescence lifetime of the Ru2+ complex attached to the zeolite is reduced by a
      factor of 30 when Ox1 acceptor molecules are present. The fluorescence decay of
      Ox1 incorporated in zeolite L is single exponential with a lifetime of 3 ns. The
      much longer lifetime in zeolite L than in solution is due to the fact, that the
      diethyl groups are sterically restricted when the dye is inside the host.

PMID- 15472932
TI  - Chemoenzymatic preparation of optically active trans-cyclohexane-1,2-diamine
      derivatives: an efficient synthesis of the analgesic U-(-)-50,488.
AB  - Stereoespecific syntheses of (+/-)-trans-N,N-cyclohexane-1,2-diamines ((+/-)-4 a
      g) were carried out from the corresponding (+/-)-trans-N,N
      dialkylaminocyclohexanols by successive treatment with mesyl chloride and aqueous
      ammonia. The stereochemical outcome indicates the formation of a meso-aziridinium
      ion intermediate. Kinetic resolutions of diamines (+/-)-4 were efficiently
      accomplished in aminolysis reactions catalyzed by lipase B from Candida
      antarctica with ethyl acetate as the solvent and acyl donor. Acetamides and the
      remaining diamines, isolated as the benzyloxycarbonyl derivatives, were obtained
      with very high ee values (92-99%). One of the carbamates was used as a precursor
      of the analgesic U-(-)-50,488.

PMID- 15472933
TI  - Using collision-induced dissociation with corrections for the ion number of
      degrees of freedom for quick comparisons of relative bonding strength.
AB  - The number of degrees of freedom-dependent stability of ions and ion-neutral non
      covalent complexes under collision-induced dissociation (CID) conditions was
      studied in a quadrupole ion trap mass spectrometer. It was found that the
      stability of ions as probed by energy-variable CID has a linear dependence on the
      total number of degrees of freedom for the ions (or ion-neutral complexes) with
      the same (or nearly the same) bonding energy. The slope of such a stability vs
      number of degrees of freedom dependence correlates with the binding energy.
      Proton-bound amine dimers display the lowest slope as they have weak bonds.
      Breaking covalent bonds will result in much greater slopes. In addition to the
      binding energy, the vibrational frequencies of the ion also affect the stability
      vs number of degrees of freedom behavior. Studying such a dependence of the CID
      stability in a system paves the way for direct relative binding energy
      comparisons. The application of this approach is demonstrated by testing the
      relative heme affinities of anti-malaria drugs and related compounds.

PMID- 15472934
TI  - Noncovalent anchoring of asymmetric hydrogenation catalysts on a new mesoporous
      aluminosilicate: application and solvent effects.
AB  - A new Bronsted acidic aluminosilicate, AlTUD-1, with ideal characteristics for
      catalyst immobilisation (mesoporous structure, high surface area, and high
      Al(tetrahedral)/Si ratio), was used successfully for the noncovalent anchoring of
      two well-established asymmetric hydrogenation catalysts: [Rh(I)(cod)[(R,R)
      MeDuPHOS]]BF4 (1) and [Rh(I)(cod)[(S,S)-DiPAMP]]BF4 (2). The new heterogeneous
      catalysts, 1-AlTUD-1 and 2-AlTUD-1, prepared by a straightforward ion-exchange
      procedure, were highly active and selective in the asymmetric reduction of
      dimethyl itaconate (3) and methyl 2-acetamidoacrylate (4), giving enantiomeric
      excesses of up to >98%. The catalysts showed similar behaviour to their
      homogeneous counterparts. Catalyst 2-AlTUD-1 could be re-used multiple times
      without loss of enantioselectivity or activity. Leaching of Rh showed a
      significant dependence on the polarity of the solvent in which the catalysis was
      performed. By applying tert-butylmethyl ether (MTBE) as solvent, the loss of Rh
      could be reduced to <0.1%. The solvent also had a noteworthy effect on the
      enantioselectivity in the hydrogenation of 4 (an effect not seen with 3 as
      substrate), that is, in MeOH the ee was 92%, in MTBE it dropped to 26% when using
      2-AlTUD-1 as catalyst.

PMID- 15472935
TI  - Multifunctionalization of synthetic polymer systems through self-assembly.
AB  - A straightforward methodology towards the replacement of covalent strategies for
      the synthesis of multifunctional synthetic materials with a self-assembling
      strategy that employs multiple noncovalent recognition units to attach multiple
      functional molecules to a polymeric scaffold is outlined. Design requirements,
      advantages, and potential applications, as well as the possibility of rapid
      optimization of materials during the manufacturing process as a result of the
      parallel character of self-assembly, are presented. While still in its infancy,
      this novel methodology may overcome several shortcomings of current covalent
      multifunctionalization strategies and may yield highly complex materials that are
      extremely difficult or impossible to fabricate with current methods.

PMID- 15472936
TI  - Readily prepared metallo-supramolecular triple helicates designed to exhibit spin
      crossover behaviour.
AB  - New dinuclear supramolecular cylinders have been designed to exhibit spin
      crossover behaviour, a form of molecular bistability. This has been achieved
      within the framework of our imine-based approach to supramolecular architecture
      by switching from pyridylimine systems to imidazolimines. Spin-crossover
      behaviour is achieved while retaining the simplicity and ease-of-synthesis of our
      molecular design. The imidazole groups used also introduce additional NH groups
      that engage in hydrogen-bonding to anions and solvents. In the case of the
      iron(II) tetrafluoroborate complex this hydrogen bonding links supramolecular
      cylinders into an extended two-dimensional array. Consistent with this, a sharper
      spin-crossover transition is observed for this compound than for the
      corresponding hexafluorophosphate salt. More subtle anion effects are indicated
      in the perchlorate salt which gives a two-step spin conversion, thereby
      displaying tristability.

PMID- 15472937
TI  - Room-temperature surface-erosion route to ZnO nanorod arrays and urchin-like
      assemblies.
AB  - A solution surface-erosion route was successfully employed to produce one
      dimensional (1D) ZnO nanostructures. ZnO nanorod arrays and three-dimensional
      urchin-like assemblies could be selectively obtained with different
      manipulations. In this process, zinc foil was introduced to an organic solution
      system and acted both as a reactant and substrate to support the 1D
      nanostructures obtained. This method, without any template, apparatus,
      surfactants, or additional heterogenous substrates, has greatly simplified the
      preparation of oriented 1D ZnO nanostructures. In particular, this simple route
      could be carried out at room temperature over a period as short as several
      minutes, thus it could be conveniently transferred to industrial applications.
      The possible formation mechanism, erosion process, and influence factors were
      also investigated.

PMID- 15472938
TI  - Two-component dendritic gel: effect of stereochemistry on the supramolecular
      chiral assembly.
AB  - The self-assembly of diaminododecane solubilised by four different stereoisomeric
      dendritic peptides to form gel-phase materials in toluene was investigated. The
      second generation dendritic peptides were based on D- and L-lysine building
      blocks, and each contained three chiral centres. By designing dendritic peptides
      in which the configurations of the chiral centres were modified, and applying
      them as gelator units, the assembly of stereoisomers could be investigated. In
      all cases, the self-assembly of gelator units resulted in macroscopic gelation.
      However, the degree of structuring was modulated by the stereoisomers employed,
      an effect which changed the morphology and macroscopic behavior of the self
      assembled state. Enantiomeric (L,L,L or D,D,D) gelator units formed fibrous
      molecular assemblies, whilst the racemic gel (50 % L,L,L : 50 % D,D,D) formed a
      flat structure with a "woven" appearance. Gelator units based on L,D,D or D,L,L
      dendritic peptides also formed fibrous assemblies, but small-angle X-ray
      scattering indicated significant morphological differences were caused by the
      switch in chirality. Furthermore, the macroscopic stability of the gel was
      diminished when these peptides were compared with their L,L,L or D,D,D analogues.
      In this paper it is clearly shown that individual stereocentres, on the molecular
      level, are directly related to the helicity within the fibre. It is argued that
      the chirality controls the pattern of hydrogen bonding within the assembly, and
      hence determines the extent of fibre formation and the macroscopic gel strength.

PMID- 15472939
TI  - C-C double- and triple-bond formation from reactions of B atoms with CO:
      experimental and theoretical characterization of OBBCCO and OBCCBO molecules in
      solid argon.
AB  - Reactions of boron atoms with CO molecules in solid argon form the following
      boron carbonyl species (which have been reported earlier): BCO, BBCO, OCBBCO,
      B(CO)2, and B4(CO)2. The OCBBCO molecule underwent a photochemical rearrangement
      where CO was activated to form the OBBCCO and OBCCBO molecules. The new molecules
      were identified on the basis of isotopic IR studies with 10B, 11B, 13C16O,
      12C18O, and carbon dioxide mixtures in addition to comparison with quantum
      chemical calculations of isotopic frequencies. Theoretical analyses showed that
      the OBBCCO and OBCCBO molecules are linear with C-C double and triple bonding,
      respectively, and lie at a much lower energy than the linear OCBBCO structure.

PMID- 15472940
TI  - From allylic alcohols to aldols by using iron carbonyls as catalysts:
      computational study on a novel tandem isomerization-aldolization reaction.
AB  - The tandem isomerization-aldolization reaction between allyl alcohol and
      formaldehyde mediated by [Fe(CO)3] was studied with the density functional B3LYP
      method. Starting from the key [(enol)Fe(CO)3] complex, several reaction paths for
      the reaction with formaldehyde were explored. The results show that the most
      favorable reaction path involves first an enol/allyl alcohol ligand-exchange
      process followed by direct condensation of formaldehyde with the free enol.
      During this process, formation of the new C-C bond takes place simultaneously
      with a proton transfer between the enol and the aldehyde. Therefore, the role of
      [Fe(CO)3] is to catalyze the allyl alcohol to enol isomerization affording the
      free enol, which adds to the aldehyde in a carbonyl-ene type reaction. Similar
      results were obtained for the reaction between allyl alcohol and acetaldehyde.

PMID- 15472941
TI  - Gaseous H5P2O8- ions: a theoretical and experimental study on the hydrolysis and
      synthesis of diphosphate ion.
AB  - The structure and reactivity of gaseous H5P2O8- ions obtained from the chemical
      ionization (CI) of an H4P2O7/H2O mixture and from electrospray ionization (ESI)
      of CH3CN/H2O/H4P2O7 solutions were investigated by Fourier transform ion
      cyclotron (FTICR) and triple quadrupole mass spectrometry. Theoretical
      calculations performed at the B3LYP/6-31+G* level of theory and collisionally
      activated dissociation (CAD) mass spectrometric results allowed the ionic
      population obtained in the CI conditions to be structurally characterized as a
      mixture of gaseous [H3P2O7...H2O]-, [H3PO4...H2PO4]-, and [PO3...H3PO4...H2O]-
      clusters. The energy profile emerging from theoretical calculations affords
      insight into the mechanism of diphosphate ion hydrolysis and synthesis.

PMID- 15472942
TI  - Novel metathesis catalysts based on ruthenium 1,3-dimesityl-3,4,5,6
      tetrahydropyrimidin-2-ylidenes: synthesis, structure, immobilization, and
      catalytic activity.
AB  - The synthesis of novel ruthenium-based metathesis catalysts containing the
      saturated 1,3-bis(2,4,6-trimethylphenyl)-3,4,5,6-tetrahydropyrimidin-2-ylidene
      ligand, that is, [RuCl2(NHC)[=CH-2-(2-PrO)-5-NO(2)-C6H3]] (1) and
      [Ru(CF3COO)2(NHC)[=CH-2-(2-PrO)-5-NO2-C6H3]] (2) (NHC=1,3-bis(2,4,6
      trimethylphenyl)-3,4,5,6-tetrahydropyrimidin-2-ylidene) is described. Both
      catalysts are highly active in ring-closing metathesis (RCM) and ring-opening
      cross-metathesis (ROCM). Compound 1 shows moderate activity in enyne metathesis.
      Compound 2 is not applicable to enyne metathesis since it shows high activity in
      the cyclopolymerization of diethyl dipropargylmalonate (DEDPM). Poly(DEDPM)
      prepared by the action of 2 consists of 95% five-membered rings, that is,
      poly(cyclopent-1-enevinylene)s, and 5 % of six-membered rings, that is,
      poly(cyclohex-1-ene-3-methylidene)s. The polymerization proceeds in a nonliving
      manner and results in polyenes with broad polydispersities (1.9< or =PDI< or
      =2.3). Supported analogues of 2 were prepared by immobilization on hydroxymethyl
      Merrifield resin and a monolithic support derived from ring-opening-metathesis
      polymerization (ROMP). Catalyst loadings of 1 and 2.5%, respectively, were
      obtained. Both supported versions of 2 showed excellent reactivity. With 0.24-2%
      of the supported catalysts, yields in RCM and ROCM were in the range of 76-100%.
      Leaching of ruthenium was low and resulted in Ru contaminations of the products
      of less than 0.000014% (0.14 ppm).

PMID- 15472943
TI  - Lanthanide(III) complexes of DOTA-glycoconjugates: a potential new class of
      lectin-mediated medical imaging agents.
AB  - The synthesis and characterization of a new class of DOTA (1,4,7,10
      tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane) monoamide-linked
      glycoconjugates (glucose, lactose and galactose) of different valencies (mono, di
      and tetra) and their Sm(III), Eu(III) and Gd(III) complexes are reported. The 1H
      NMR spectrum of Eu(III)-DOTALac2 shows the predominance of a single structural
      isomer of square antiprismatic geometry of the DOTA chelating moiety and fast
      rotation about the amide bond connected to the targeting glycodendrimer. The in
      vitro relaxivity of the Gd(III)-glycoconjugates was studied by 1H nuclear
      magnetic relaxation dispersion (NMRD), yielding parameters close to those
      reported for other DOTA monoamides. The known recognition of sugars by lectins
      makes these glycoconjugates good candidates for medical imaging agents (MRI and
      gamma scintigraphy).

PMID- 15472944
TI  - Regioselectivity in iron-catalyzed [2+2+1] cycloadditions: a DFT investigation of
      substituent effects in 1,4-diazabutadienes.
AB  - The transition-metal-catalyzed [2+2+1] cycloaddition reaction of 1,4
      diazabutadienes, in which the imine-carbon atoms are part of an oxazine ring
      system, with ethylene and carbon monoxide leads to the regioselective formation
      of pyrrolidinone derivatives. To explain this regioselectivity, the transition
      states and intermediates of the rate-determining step of the catalysis are
      determined by high-level DFT calculations. The experimentally observed
      regioselectivity is consistent with the lower activation energy of the addition
      of ethylene towards the carbon atom next to the oxazine oxygen atom. Furthermore,
      the activation barrier of a conceivable back reaction is higher for the
      intermediates with the experimentally observed regioselectivity. These
      thermodynamic and kinetic arguments at first sight appear to be confirmed by the
      calculated NPA charges in the transition states, which reveal that the
      differences in these charges are greatest for those transition states that lead
      to the formation of the energetically favored transition structures.
      Nevertheless, calculations of analogous transition structures and reaction
      products starting from 1,4-diazabutadienes with a 2-fluoro, 2-hydroxo or 2-amino
      substituent revealed that the regioselectivity is not determined by the
      electronegativity of the heteroatom and thus by the differences in the NPA
      charges or the resulting Coulombic interactions in the transition structures. The
      main reason for the observed regioselectivities is the pi-donor ability of the
      substituent to contribute to a delocalized pi system incorporating the adjacent
      imine moiety. The increasing pi-donor capability results in decreased reactivity
      of this moiety and increases the (relative) reactivity of the second imine group.
      This effect can even overcompensate for strong intramolecular Coulombic
      attractions in the transition structures.

PMID- 15472945
TI  - Oxidation of CS4 by AsBr4+: the unexpected formation of the simple CS2Br3+
      carbenium ion.
AB  - During the preparation of AsBr4(+)[Al(OR)4]-, the novel carbocation CS2Br3+ was
      synthesized by reaction of AsBr3, Br2, CS2, and Ag[Al(OR)4] (R=C(CF3)3).
      CS2Br3(+)[Al(OR)4]- was characterized by its crystal structure, NMR and IR
      spectroscopy, and quantum chemical calculations (including COSMO solvation
      enthalpies). Additional experiments as well as the computed thermodynamics
      indicated two likely reaction pathways: Ag(+) +2Br2 +CS2-->CS2Br3(+) +AgBr and
      the direct 4e- oxidation reaction AsBr4(+) +CS2-->CS2Br3(+) + 1/6As6Br6. Both
      reactions were observed experimentally and were calculated to be exergonic in
      solution by -226 and -56 kJ mol(-1) respectively. As a result of charge
      delocalization the C-S and C-Br distances in the cation are shortened by 0.06 to
      0.08 A; the S--Br distances are also slightly shortened indicating a
      delocalization of the charge also to the bromine atoms in the (S--Br moieties.
      Based on an analysis of the cation-anion contacts as well as quantum chemical MP2
      calculations, a delocalization model as a planar 10 pi electron system is
      discussed and the pi molecular orbitals are given. It will be shown that the
      electronic situation of CS2Br3+ is very close to that in CBr3+, that is, the
      properties of SBr moieties and Br atoms as pi donors towards a formal C+ center
      are comparable.

PMID- 15472946
TI  - Multiple binding modes of the camptothecin family to DNA oligomers.
AB  - The binding constants of camptothecin, topotecan and its lactone ring-opened
      carboxylate derivative to DNA octamers were measured by UV and NMR spectroscopy.
      The self-association of topotecan (TPT) was also measured. The carboxylate form
      of TPT binds in the same way as the lactone, but more weakly. Titration of TPT
      into d(GCGATCGC)2 shows a preferred location stacked onto the terminal G1 base.
      However, the intermolecular NOEs cannot be reconciled with a single conformation
      of the complex, and suggest a model of a limited number of conformations in fast
      exchange. MD calculations on four pairs of starting structures with TPT stacked
      onto the G1-C8 base pair in different orientations were therefore performed. The
      use of selected experimental "docking" restraints yielded ten MD trajectories
      covering a wide conformational space. From a combination of calculated free
      energies, NOEs and chemical shifts, some of the structures produced could be
      eliminated, and it is concluded that the data are consistent with two major
      families of conformations in fast exchange. One of these is the conformation
      found in a crystal of a TPT/DNA/topoisomerase I ternary complex [Proc. Natl.
      Acad. Sci. USA 2002, 99, 15 387-15 392].

PMID- 15472947
TI  - RNA is more UV resistant than DNA: the formation of UV-induced DNA lesions is
      strongly sequence and conformation dependent.
AB  - DNA and RNA hairpins, which represent well-folded oligonucleotide structures,
      were irradiated and the amount of damaged hairpins was directly quantified by
      using ion-exchange HPLC. The types of photoproducts formed in the hairpins were
      determined by ESI-HPLC-MS/MS experiments. Irradiation of hairpins with
      systematically varied sequences and conformations (A versus B) revealed
      remarkable differences regarding the amount of photolesions formed. UV-damage
      formation is, therefore, a strongly sequence and conformation dependent process.

PMID- 15472948
TI  - Intermediate precision study on a capillary electrophoretic method for
      chlortetracycline.
AB  - We describe an intermediate precision study on a capillary electrophoretic (CE)
      method for chlortetracycline. It is shown how in one setup the influence of the
      factors time, analyst, and equipment on the precision can be investigated. As
      different types of CE equipments were included, the transferability of the method
      could be examined. Both the qualitative and quantitative aspect of the method
      were investigated. It was shown that small adaptations in method conditions can
      have a large influence on the method transferability. Although the method could
      be transferred to different types of CE equipments, the precision of the method
      was found poor when the between-equipment variability was taken into account.
      Despite the use of an internal standard, the between injection variability was
      found rather high.

PMID- 15472950
TI  - Separation of positional isomers by cucurbit[7]uril-mediated capillary
      electrophoresis.
AB  - A novel macrocyclic molecule, cucurbit[7]uril (CB[7]) was for the first time
      employed as an additive in capillary electrophoresis (CE). In similarity to other
      macrocyclic molecules, such as crown ethers, cyclodextrins (CDs) and calixarenes,
      CB[7] can form inclusion complexes with a variety of guest molecules due to its
      inner cavity. Thus, it can be used like other macrocyclic molecules to manipulate
      selectivities in CE. During the running process, CB[7] bears a positive charge
      under the studied pH range (pH 2.5-7) and can be adsorbed onto the inner wall of
      a fused-silica capillary, leading to a reversal of the electroosmotic flow (EOF).
      Electrophoretic behaviors of nitrotoluene, nitrophenol, nitroaniline, and
      methylaniline isomers were studied under various conditions. The electrophoretic
      separations of the isomers can be accomplished with a buffer containing CB[7].
      Furthermore, a probable separation mechanism in the presence of CB[7] was also
      proposed.

PMID- 15472951
TI  - Purification of the Escherichia coli K5 capsular polysaccharide and use of high
      performance capillary electrophoresis to qualitative and quantitative monitor the
      process.
AB  - A rapid, highly sensitive, and reproducible high-performance capillary
      electrophoresis (HPCE) method (electrokinetic chromatography with sodium dodecyl
      sulfate) is described for the determination of the polysaccharide from the
      uropathogenic Escherichia coli K5 bacteria Bi8337/41 010:K5:H4. This natural
      polysaccharide having the structure of a desulfo-heparin composed of -4)
      alphaGlcUA-(1,4)-alpha-GlcNAc-(1- is separated (GlcUA = D-glucuronic acid; GlcNAc
      = D-glucosamine) and qualitatively and quantitatively determined within 20 min on
      an uncoated fused-silica capillary using normal polarity at 20 kV and detection
      at 200 nm. A linear relationship (correlation coefficient > approximately 0.99)
      was found for the polymer over a wide range of concentrations, from approx. 60 to
      1500 ng, with a detection sensitivity of < approximately 60 ng. Furthermore, this
      qualitative and quantitative HPCE approach was applied to the K5 extraction and
      purification process from cultured bacteria in several stages. HPCE was also able
      to separate several molecular species mainly due to the presence of
      polysaccharides of distinct and increasing mean chain lengths. A linear
      relationship was found for migration time and log molecular mass of different K5
      polysaccharide species, and this model was used to calculate the molecular mass
      of the main K5 species producing a result of approx. 17,000, also confirmed by
      high-performance size-exclusion chromatography analysis, yielding approx. 17 200.

PMID- 15472952
TI  - Modified micellar electrokinetic chromatography in the analysis of catechins and
      xanthines in chocolate.
AB  - Modified micellar electrokinetic chromatography (MEKC) analysis of monomeric
      flavanols (catechin and epicatechin) and methylxanthines (caffeine and
      theobromine) in chocolate and cocoa was performed by using sodium dodecyl sulfate
      (SDS) as a principal component of the running buffer. Because of the reported
      poor stability of catechins in alkaline solutions, acidic conditions (pH 2.5)
      were chosen and consequently the electroosmotic flow (EOF) was significantly
      suppressed; this resulted in a fast anodic migration of the analytes partitioned
      into the SDS micelles. Under these conditions, variations of either pH value in
      acidic range or SDS concentration, showed to be not suitable to modulate the
      selectivity. To overcome this limit, use of additives to the SDS-based running
      buffer was successfully applied and three different systems were optimized for
      the separation of (+)-catechin, (-)-epicatechin, caffeine, and theobromine in
      chocolate and cocoa powder samples. In particular, two mixed micelle systems were
      applied; the first consisted of a mixture of SDS and 3-[(3
      cholamidopropyl)dimethylammonio]-1-propansulfonate (CHAPS) with a composition of
      90 mM and 10 mM, respectively; the second was SDS and taurodeoxycholic acid
      sodium salt (TDC) with a composition of 70 mM and 30 mM, respectively. A further
      MEKC approach was developed by addition of 10 mM hydroxypropyl-beta-cyclodextrin
      (HP-beta-CD) to the SDS solution (90 mM); it provided a useful cyclodextrin(CD)
      modified MEKC. By applying the optimized conditions, different separation
      profiles of the flavanols and methylxanthines were obtained showing interesting
      potential of these combined systems; their integrated application showed to be
      useful for the identification of the low level of (+)-catechin in certain real
      samples. The CD-MEKC approach was validated and applied to the determination of
      catechins and methylxanthines in aqueous extracts from four different commercial
      chocolate types (black and milk) and two cocoa powders.

PMID- 15472953
TI  - Analysis of insecticidal proteins from Bacillus thuringiensis and recombinant
      Escherichia coli by capillary electrokinetic chromatography.
AB  - Bacillus thuringiensis and recombinant Escherichia coli proteinaceous protoxins
      were subject to proteolysis and analyzed by capillary electrokinetic
      chromatography. Three resulting toxins (65 kDa) were baseline-resolved within 22
      min using a 10 mM borate, pH 11 separation buffer consisting of 25 mM sodium
      dodecyl sulfate (SDS) and 30 mM phytic acid. The toxins displayed differential
      interactions with the SDS and phytic acid phases to effect their separation. The
      ion-pairing interaction between the analyte and phytic acid was also useful in
      preventing adsorption to the capillary walls and thus enhanced separation
      resolution and efficiency. The use of electrokinetic chromatography allows
      achievement of the separation in a significantly shorter time than conventional
      high-performance liquid chromatography (HPLC) using a diethylaminoethyl (DEAE)
      weak-anion exchanger.

PMID- 15472954
TI  - Pyrimidine 5'-nucleotidase activities detected in real samples by means of
      micellar electrokinetic chromatography.
AB  - A micellar electrokinetic chromatographic method that allows simultaneous
      determination of both nucleotidase and transferase activities of cytosolic 5'
      nucleotidase III is presented. This electrophoretic approach was successfully
      applied to human erythrocyte lysates to monitor the enzyme activities indicated
      above, using either physiological substrate or the nucleoside analogue 3'-azido
      3'-deoxythymidine as the phosphate acceptor.

PMID- 15472955
TI  - Separation of isomers of acyl glucuronides using micellar electrokinetic
      capillary chromatography in dynamically coated capillaries.
AB  - The acyl glucuronide metabolites of endogenous as well as of xenobiotic compounds
      may undergo isomerization in vitro as well as in the human body. The parent acyl
      glucuronide and the isomerization products may react with endogenous protein to
      form products which in worst cases may act as antigens and thus create an
      allergic response. In the present paper new methods based on micellar
      electrokinetic or microemulsion electrokinetic chromatography for the separation
      of all isomerization products as well as the hydrolysis product of acyl
      glucuronides are described. In order to perform the separation at lower pH values
      in a reasonable time dynamically coated capillaries were used. This enables the
      electroosmotic flow to be high and constant even at low pH. The methods were
      developed using S-naproxen-beta-1-O-acyl glucuronide as the model substance. The
      assignment of the single peaks in the electropherogram was performed tentatively
      based on the sequential appearance of the isomerization products with time.

PMID- 15472956
TI  - Microemulsion electrokinetic chromatography for the analysis of acrylamide in
      food.
AB  - The influence of microemulsion electrokinetic chromatography (MEEKC) operating
      conditions, such as the type of water-immiscible alcohol, aqueous phosphate
      buffer concentration, pH, as well as the addition of methanol and 2-propanol, on
      acrylamide migration has been studied. These parameters have been optimized
      taking into account the presence of matrix signals, in order to avoid the
      interference of these peaks in acrylamide determination. The best separations
      were achieved using a microemulsion consisting of 0.8% m/v n-amyl alcohol, 3.3%
      m/v sodium dodecyl sulfate (SDS), 6.6% m/v 1-butanol, and 89.3% m/v 40 mM
      phosphate buffer at pH 6.5 working at 15 kV in uncoated silica capillaries.
      Linear calibration curves over the range studied (1.25-125 microg x mL(-1)), the
      detection limit (0.70 microg x mL(-1)), and both run-to-run (up to 3.4% for
      concentration and 1.6% for time values) and day-to-day precision (lower than
      11.6% for concentration) have been established. Finally, the applicability of the
      MEEKC method developed has been demonstrated by analyzing levels of acrylamide
      present in samples of home-made French fries.

PMID- 15472957
TI  - Separation of enantiomers in microemulsion electrokinetic chromatography using
      chiral alcohols as cosurfactants.
AB  - A novel chiral microemulsion, which involved the use of chiral alcohols as
      cosurfactants, was demonstrated for the enantiomeric separation of a number of
      pharmaceutical drugs in microemulsion electrokinetic chromatography (MEEKC). The
      chiral alcohols investigated were optically active 2-alkanols, with the alkyl
      chain length having carbon number ranging from 4 to 7. The data indicated that,
      except for R-(-)-2-butanol, the use of R-(-)-2-pentanol, R-(-)-2-hexanol or R-(-)
      2-heptanol as the chiral cosurfactant resulted in the baseline or partial
      resolution of most of the test solutes, i.e., (+/-)-norephedrine, (+/-)
      ephedrine, DL-nadolol, and DL-propranolol. In addition to the chain length of the
      chiral 2-alkanols, the effects of other experimental conditions, such as the
      concentration and chirality of the 2-alkanols, as well as the pH of the run
      buffer and the oil phase of the microemulsion, on the enantiomeric separation of
      the test solutes were also investigated. An interesting finding was that the
      water-immiscible organic solvent (oil core) within the microemulsion droplets
      appeared to play an important role in the chiral separation mechanism. Also, the
      importance of hydrogen bonding between the test solutes ((+/-)-ephedrine and
      related compounds) and the chiral microemulsion was demonstrated, as it was not
      possible to resolve a pair of enantiomers which lacked a beta-amino proton (i.e.,
      (+/-)-N-methyl ephedrine) under optimized run buffer conditions (e.g., 5.0% R-(-)
      2-hexanol, 0.8% n-octane, and 3.5% SDS in 90.7% borate buffer at pH 9.2).

PMID- 15472958
TI  - Analyses of preservatives by capillary electrochromatography using methacrylate
      ester-based monolithic columns.
AB  - Five common food preservatives were analyzed by capillary electrochromatography,
      utilizing a methacrylate ester-based monolithic capillary as separation column.
      In order to optimize the separation of these preservatives, the effects of the
      pore size of the polymeric stationary phase, the pH and composition of the mobile
      phase on separation were examined. For all analytes, it was found that an
      increase in pore size caused a reduction in retention time. However, separation
      performances were greatly improved in monolithic columns with smaller pore sizes.
      The pH of the mobile phase had little influence on separation resolution, but a
      dramatic effect on the amount of sample that was needed to be electrokinetically
      injected into the monolithic column. In addition, the retention behaviors of
      these analytes were strongly influenced by the level of acetonitrile in the
      mobile phase. An optimal separation of the five preservatives was obtained within
      7.0 min with a pH 3.0 mobile phase composed of phosphate buffer and acetonitrile
      35:65 v/v. Finally, preservatives in real commercial products, including cold
      syrup, lotion, wine, and soy sauces, were successfully determined by the
      methacrylate ester-based polymeric monolithic column under this optimized
      condition.

PMID- 15472959
TI  - Effect of surfactant concentration and buffer selection on chromatographic
      figures of merit in chiral microemulsion electrokinetic chromatography.
AB  - The enantiomeric resolution of 15 different pharmaceutical compounds was explored
      using chiral microemulsion electrokinetic chromatography (MEEKC). The
      microemulsion employed was comprised of the chiral surfactant
      dodecoxycarbonylvaline (DDCV), 1-butanol, and ethyl acetate, at an initial
      composition of 1% w/v:1.2% v/v:0.5% v/v, respectively. The effect of varying the
      background buffer composition, voltage, and ultimately the surfactant
      concentration and/or aggregate phase ratio were examined. Changing from a
      zwitterionic buffer ((2-[2-amino-2-oxoethyl)amino]ethanesulfonic acid, ACES) to
      the same concentration of phosphate buffer improved the efficiency and decreased
      overall analysis time, but also resulted in a decrease in chiral resolution.
      Furthermore, using phosphate buffer while simultaneously increasing the percent
      DDCV from 1 to 4% increased the efficiencies from a range of 34,000 to 59,000 N/m
      to a range of 160,000 to 400,000 N/m. While the enantioselectivities did not
      change significantly, the improvement in efficiencies, elution range, and
      retention factors provided an increase in both resolution and the number of
      enantiomers that were separated. Using an optimized microemulsion comprised of
      phosphate buffer and 4% DDCV, chiral separation was achieved for all 11 pairs of
      enantiomers, with a resolution ranging from 0.90 to 4.71. Moreover, the average
      resolution doubled in going from nonoptimized to optimized conditions for five of
      the eleven compounds. Finally, a comparison was made of the effect of increasing
      only the surfactant concentration by a factor of 4 versus increasing the overall
      composition (or phase ratio) by a factor of 4. Ultimately, the microemulsion
      containing 4% DDCV provided a larger elution range, greater resolution, and more
      optimal retention than that provided by the 4x phase increase.

PMID- 15472960
TI  - Investigation of the novel mixed-mode stationary phase for capillary
      electrochromatography. II. Separation of amino acids and peptides on sulfonated
      naphthalimido-modified silyl silica gel.
AB  - The potential of 3-(4-sulfo-1,8-naphthalimido)propyl-modified silyl silica gel
      (SNAIP) as a mixed-mode stationary phase for capillary electrochromatography
      (CEC) was investigated for the separation of charged analytes, taking four amino
      acids (tyrosine, phenylalanine, tryptophan, histidine) as model analytes. The
      elution process of these charged analytes in CEC with SNAIP was dominated by a
      combination of both electrophoretic process and chromatographic process involving
      hydrophobic as well as electrostatic interactions. In order to study the
      retention mechanism, the CEC retention factor k* and the velocity factor ke* were
      measured for the amino acids, which allowed the assessment of the respective
      contribution from the differential processes underlying the separation. Migration
      and retention could be mediated by changing various mobile phase compositions,
      including buffer pH, buffer concentration, and concentration of organic solvent.
      Based on the results obtained by separation of the amino acids, the separation of
      eight peptides (Gly-Val, Gly-Phe, Gly-Ile, Gly-His, Gly-Lys, Lys-Lys, Gly-Gly
      Gly, Gly-Gly-His) was attempted. A good separation was achieved under an
      isocratic elution with a mobile phase consisting of 35 mM phosphate buffer (pH
      3.8) and 40% methanol.

PMID- 15472961
TI  - Rapid determination of aliphatic amines in water samples by pressure-assisted
      monolithic octadecylsilica capillary electrochromatography-mass spectrometry.
AB  - A pressure-assisted capillary chromatography-mass spectrometry method based on
      the use of a monolithic octadecylsilica (ODS) capillary is proposed for the
      determination of aliphatic amines. A 25 mM citric acid buffer containing 10%
      methanol is used as running electrolyte. Separation is achieved by simultaneously
      applying a capillary electrophoresis (CE) voltage of 13 kV and an overimposed
      pressure of 8 bar. The use of pressure is required to ensure stable electrospray
      conditions. Analysis times are reduced by using a capillary column consisting of
      a 30 cm long monolithic silica capillary column bound with ODS and a fused-silica
      capillary column also 30 cm long. The proposed method was successfully applied to
      the determination of low-molecular-weight aliphatic amines in tap and river
      water. The analysis of real samples requires cleanup and preconcentration, which
      can be performed automatically by inserting a minicolumn in the replenishment
      system of the commercial instrument.

PMID- 15472962
TI  - Development and in situ synthesis of monolithic stationary phases for
      electrochromatographic separations.
AB  - Organic monolithic stationary phases have been synthesized in UV-transparent
      fused-silica capillaries, which have been used as test format of microfabricated
      device channels. The columns have been prepared by in situ polymerization of
      butyl acrylate, lauryl acrylate, 1,3-butanediol diacrylate, and 2-acrylamido-2
      methyl-1-propanesulfonic acid (AMPS) in a ternary porogenic solvent. The
      resulting stationary phases have been tested in capillary electrochromatography
      and exhibited reversed-phase chromatography behavior toward neutral solutes. Van
      Deemter plots of phenylureas and polycyclic aromatic hydrocarbons, selected as
      model analytes, have been determined to study the influence of various
      polymerization and separation parameters on properties of the monoliths. The
      amount of AMPS and the nature of monomers in the polymerization solution have
      been thus adjusted. It has been observed that the ionic strength of the mobile
      phase may affect significantly the efficiency of the separation. The effect of
      the percentage of acetonitrile in the mobile phase on efficiency and permeability
      of the organic monoliths has also been investigated. Efficiencies greater than
      300,000 plates/m have been obtained with the test compounds. Stability and
      reproducibility have been extensively studied.

PMID- 15472963
TI  - Proline-coated column for the capillary electrochromatographic separation of
      amino acids by in-column derivatization.
AB  - With 3-trimethoxysilylpropyl chloride as the spacer, a proline-coated capillary
      column was prepared for the capillary electrochromatographic (CEC) separation of
      amino acids by in-column derivatization. Nine standard mixtures, including
      aspartic acid, glutamic acid, valine, phenylalanine, alanine, isoleucine,
      leucine, tyrosine, and tryptophan, were injected. o-Phthalaldehyde (OPA), OPA/2
      mercaptoethanol (2-ME) and OPA/N-acetylcysteine (NAC) in borate buffer were
      tested as the derivatizing agent. Among them, OPA (50 mM) in borate buffer (pH
      9.5, 50 mM) gave the best performance. The formation of isoindole could be
      detected by UV detection. The sandwich-type injection was carried out in
      hydrostatic mode (10 cm) with the program R(10 s)S(10 s) R(10 s)W(10 min) with R,
      S, and W being the reagent, sample, and waiting times. Mesityl oxide, benzyl
      alcohol, and acetone showed some interaction with the column. A current
      monitoring method was used instead of the determination of the electroosmotic
      flow (EOF). The direction of EOF was from anode to cathode even under acidic
      condition lower than the pI value (6.31) of the bonded group due to some
      unreacted silanol groups. Some parameters including pH, nature, and concentration
      of the mobile phase and the effect of organic modifier with regard to the CEC
      separation were investigated. With the proline-coated column (75 (50) cm x 75
      microm ID) the best separation was performed in phosphate buffer (pH 4.00, 100
      mM) with an applied voltage of -15 kV. The established method was also compared
      with those precolumn derivatized prior to the separation with proline-coated
      column as well as with in-capillary derivatization and separation with a bare
      fused-silica column.

PMID- 15472964
TI  - Capillary electrophoresis studies on the aggregation process of beta-amyloid 1-42
      and 1-40 peptides.
AB  - The possibility to monitor, in solution, the steps of beta-amyloid (Abeta)
      nucleation and therefore to describe this dynamic process by using capillary
      electrophoresis and under optimized experimental conditions is described.
      Striking differences in the electrophoretic patterns of Abeta 1-42 and Abeta 1-40
      over time are here shown, and different aggregation states are elucidated, which
      reflect the very diverse oligomerization behavior of two very similar peptides.
      The isolation of one aggregated species of high molecular weight by
      ultracentrifugation allowed us to assess its role as toxic oligomer. The
      perturbation of the existing equilibrium among the identified species by the
      addition of small molecules can in principle interfere with the aggregation
      process of the peptides and ultimately prevent the plaque formation in vitro.

PMID- 15472965
TI  - New particle-loaded monoliths for chiral capillary electrochromatographic
      separation.
AB  - Fritless particle-loaded monoliths for chiral capillary electrochromatographic
      (CEC) separation were prepared. Silica particles containing a chiral selector are
      suspended in a monomer solution, which is drawn into the capillary followed by in
      situ polymerization. Thereby the silica-based particles containing the chiral
      selector are embedded in a nonchiral continuous bed. This kind of chiral
      stationary phase is inexpensive, easy, and reproducible to prepare and
      circumvents the preparation of frits. As a model, teicoplanin aglycone as chiral
      selector bonded to 3 microm silica particles was used. The applicability of this
      approach is demonstrated by means of the chiral separation of aliphatic and
      aromatic amino acids and dipeptides. As a further application, the chiral
      selector ristocetin A bonded to 3 microm silica particles was used for the
      enantiomeric separation of chiral alpha-hydroxy acids. Since alpha-hydroxy acids
      migrate toward the anode, a cationic charge-providing agent was copolymerized
      with the matrix. This served to reverse the direction of the electroosmatic flow
      (EOF).

PMID- 15472966
TI  - Complexation between low-molecular-weight cationic ligands and negatively charged
      polymers as studied by capillary electrophoresis frontal analysis.
AB  - The potential of using capillary electrophoresis frontal analysis for the study
      of low-molecular-weight ligand-polyelectrolyte interactions was assessed. The
      interaction of the ligands 1-propylpyridinium bromide, 2-propylisochinolinium
      bromide, and paraquat with the polymer dextran sulfate was investigated as a
      function of polymer concentration and ionic strength of the buffer solution.
      Linear binding isotherms were obtained and association constants were determined.
      The complex formation was independent of the dextran sulfate concentration at low
      ionic strength. Ligand-polyelectrolyte interactions were strongly dependent on
      the ionic strength. The interaction of the divalent cation paraquat with the
      dextran sulfate was much stronger than the interactions of the monovalent
      cationic ligands with the polyelectrolyte. The binding data obtained were in
      accord with results obtained by equilibrium dialysis. Capillary electrophoresis
      frontal analysis has the potential to become a valuable tool for characterization
      of ligand-polyelectrolyte interactions in drug design as well as in other areas.

PMID- 15472967
TI  - High-throughput capillary electrophoresis frontal analysis method for the study
      of drug interactions with human serum albumin at near-physiological conditions.
AB  - The application of the short-end capillary injection to capillary electrophoresis
      frontal analysis (CE-FA) to study the interaction between basic, neutral and acid
      drugs towards human serum albumin (HSA) at near-physiological conditions is
      presented. The compounds selected display a wide range of binding affinities and
      the results obtained were in good agreement with those reported in the
      literature. An equation for the estimation of the number of primary binding sites
      and their corresponding affinity constants is developed isolating the
      experimentally measured variables in just one axis. The proposed CE-FA method to
      screen drug interactions with HSA under physiological conditions is simple, rapid
      and cost-effective what may facilitate its implementation in the drug discovery
      process.

PMID- 15472968
TI  - Continuous on-line derivatization and selective separation of D-aspartic acid by
      a capillary electrophoresis system with a continuous sample introduction
      interface.
AB  - A rapid and selective method is described for the separation of D-aspartic acid
      (D-Asp) using a continuous on-line derivatization system coupled to capillary
      electrophoresis (CE). D-Asp was derivatized using o-phthaldialdehyde/N-acetyl-L
      cysteine (OPA/NAC). By on-line derivatization, amino acid enantiomers were
      automatically and reproducibly converted to the UV-absorbing diastereomer
      derivatives which were separated by capillary zone electrophoresis (CZE) in the
      presence of 10 mmol/L beta-cyclodextrin (beta-CD). Under the investigated
      separation conditions, D-Asp is resolved from L-aspartic acid (L-Asp) and other
      amino acids in a standard mixture of amino acids. The separation could be
      achieved within 4 min and the sample throughput rate can reach up to 16 h(-1).
      The repeatability (defined as relative standard deviation, RSD) was 3.21%, 3.58%
      with peak area evaluation and 3.72%, 4.03% with peak height evaluation for L-Asp
      and D-Asp.

PMID- 15472969
TI  - Determination of the bacterial pathogen Edwardsiella tarda in fish species by
      capillary electrophoresis with blue light-emitting diode-induced fluorescence.
AB  - High-performance capillary electrophoresis (HPCE) has been applied to the
      identification, separation, and quantitation of intact bacteria. We demonstrate
      that a pathogen (Edwardsiella tarda) which causes systemic infection in
      commercially important fish species can be rapidly identified and determined (<
      10 min) after direct injection into fish fluid by CE blue light-emitting diode
      (LED)-induced fluorescence. SYTO 13 (488 nm/509 nm), a cell-permeable green
      nucleic acid stain, was used to stain the cells. Remarkably high efficiency (>
      1,200,000 theoretical plates/m) was achieved with this rapid and efficient CE
      method. It was found that proper sample vortexing (90 s) would be beneficial to
      disperse aggregated cells and facilitate the focusing of intact cells during
      electrophoresis. Ionization of the surface constituents of Edwardsiella tarda
      cells provided efficient surface charges for the intact cells to be separated
      from the EOF and damaged or lysed cells when the separation was performed in
      running buffer (3.94 mM Tris, 0.56 mM borate, 0.013 mM EDTA) at pH 10.5. The
      limit of detection (LOD) and recovery were found to be 4.2 x 10(4) cells/mL and
      70.0%, respectively. This proposed CE method could become an effective tool for
      diagnosis and tracking of certain diseases caused by bacteria in fish species as
      well as in human beings.

PMID- 15472970
TI  - Design and performance of a light-emitting diode detector compatible with a
      commercial capillary electrophoresis instrument.
AB  - Indirect photometric detection in capillary electrophoresis (CE) has been
      predominantly performed in the UV region, in part due to a lack of suitable high
      intensity and low-noise light sources in the visible spectral region. A new
      photometric detector based on light-emitting diodes (LEDs) as light sources and
      compatible with a commercially available CE instrument has been designed and
      constructed and its performance evaluated. The utility of this detector was
      successfully demonstrated by the indirect photometric detection of anions using a
      dye as probe and absorbance measured in the visible region. The detector
      exhibited very low baseline noise (around 0.03 mAU), stable output, and improved
      upper limit of detection linearity (502 mAU) compared with previously used LED
      detectors. The detector was tested for indirect detection of anions separated
      with an electrolyte containing 4 mM Orange G as the indirect detection probe, 10
      mM histidine as an isoelectric buffer, and 0.05% hydroxypropylmethylcellulose to
      suppress the electroosmotic flow. Extremely low detection limits were obtained
      ranging from 0.16-0.36 microM (excluding chloride 0.56 microM), with separation
      efficiencies in the range of 154,000-274,000 theoretical plates.

PMID- 15472971
TI  - Noncovalent labeling of myoglobin for capillary electrophoresis with laser
      induced fluorescence detection by reconstitution with a fluorescent porphyrin.
AB  - Traditional protein labeling reactions for capillary electrophoresis (CE) with
      laser-induced fluorescence (LIF) detection suffer from a variety of
      disadvantages. The reactions can be nonquantitative on a reasonable time scale,
      require relatively high concentrations of protein and fluorophore, and can give
      multiple reaction products that can not be separated. Herein, we describe a new
      noncovalent labeling technique that is rapid, selective for myoglobin, and gives
      a simple reaction product. Myoglobin is denatured with either 5.4 M urea or low
      pH (2.0). The denatured myoglobin releases its nonfluorescent heme group. A
      fluorescent porphyrin (protoporphyrin IX (PPIX) or its zinc (II) complex, Zn
      PPIX), is added to the mixture and the solution conditions are altered (dilute to
      0.54 M urea or adjust pH to 7.0) to allow myoglobin refolding. Upon refolding,
      the protein incorporates PPIX from solution, thus making the reaction product
      fluorescent. The experimental conditions have been optimized for both urea and
      low-pH denaturation of myoglobin. The latter procedure produces a detection limit
      of 50 nM. Alternatively, the reaction can be performed without denaturation by a
      simple exchange of the porphyrins. The use of Zn-PPIX yields the most efficient
      reaction. The low-pH reaction is unaffected by a 2000-fold excess of bovine serum
      albumin.

PMID- 15472972
TI  - Total serum protein N-glycome profiling on a capillary electrophoresis
      microfluidics platform.
AB  - We implemented 8-aminopyrene-1,3,6-trisulfonic acid (APTS)-labeled asparagine
      linked glycan (N-glycan) profiling on a microfluidic electrophoresis platform.
      Using 11.5 cm effective length etched channels and 4% linear polyacrylamide as
      the separation matrix, the major N-glycans in human serum were profiled in 12 min
      with a resolution comparable to what is achieved for these analytes on gel-based
      DNA sequencers. This demonstration suggests a practical clinical application for
      high-speed compact analyzers which might be uniquely based on microfluidic
      devices.

PMID- 15472973
TI  - Critical aspects of analysis of Micrococcus luteus, Neisseria cinerea, and
      Pseudomonas fluorescens by means of capillary electrophoresis.
AB  - Within the frame of our study we investigated Microccocus luteus, Neisseria
      cinerea, and Pseudomonas fluorescens by means of capillary zone electrophoresis
      (CZE). They form chains and clusters on a different scale, which can be reflected
      in the electropherograms. A low buffer concentration of Tris-borate and Na2EDTA
      containing a polymeric matrix of 0.0125% poly(ethylene) oxide (PEO) was used. Key
      factors were the standardization and optimization of CE conditions, buffer
      solution, and pretreatment of bacterial samples, which are not transferable to
      different bacterial strains, in general. The different compositions of the cell
      wall of on the one hand Gram-positive (M. luteus) and Gram-negative (N. cinerea)
      cocci and on the other hand Gram-negative, rod-shaped bacteria (P. fluorescens),
      are probably responsible for the different pretreatment conditions.

PMID- 15472974
TI  - Large-scale carbohydrate analysis by capillary array electrophoresis: part 1.
      Separation and scale-up.
AB  - A 96-capillary array electrophoresis (CAE) instrument has been adapted for large
      scale mono- and oligosaccharide analysis and characterization. Operational
      protocols and data processing tools have been developed to optimize the CAE
      system for this application. Effects of different additives to the running buffer
      on efficiency and capillary-to-capillary performance reproducibility have been
      studied.

PMID- 15472975
TI  - Large-scale carbohydrate analysis by capillary array electrophoresis: part 2.
      Data normalization and quantification.
AB  - Automated 96-capillary array electrophoresis (CAE) methodology described in the
      first part of the present work offered large-scale high-performance profiling of
      oligo- and monosaccharides to fulfill the needs of bioindustrial laboratories.
      Sensitivity at low nanomolar concentration, good resolving power and reliability
      achieved in the experiments is invaluable for monitoring reaction products from
      enzymatic polysaccharide digestion with numerous applications in agricultural,
      chemical and food industries. In addition to optimization of mono- and
      oligosaccharide separations in CAE system and necessary operational protocol
      modifications, capillary-to-capillary and run-to-run variation in migration time
      and signal intensity necessitated development of data normalization tools.
      Internal fluorescent standards have been incorporated into the analysis aiding
      migration time normalization and CAE trace alignment. Data processing,
      visualization, and programming tools have been developed along with
      quantification approaches.

PMID- 15472976
TI  - Capillary sieving electrophoresis-micellar electrokinetic chromatography fully
      automated two-dimensional capillary electrophoresis analysis of Deinococcus
      radiodurans protein homogenate.
AB  - We report the one- and two-dimensional (1-D and 2-D) capillary electrophoresis
      separation of Deinococcus radiodurans protein homogenate. Proteins are labeled
      with the fluorogenic reagent 3-(2-furoyl)quinoline-2-carboxaldehyde (FQ), which
      reacts with lysine residues and creates a highly fluorescent product. Detection
      is by laser-induced fluorescence. 1-D capillary sieving electrophoresis (CSE)
      produces over 150,000 plates and micellar electrokinetic capillary chromatography
      (MEKC) produces over 900,000 plates for components in a D. radiodurans protein
      homogenate. In a 2-D separation, proteins are first separated by CSE. Fractions
      are repetitively transferred to a second capillary for further separation based
      on MEKC. The 2-D separation has a approximately 550 spot capacity. Over 150
      components are partially resolved from the homogenate. Resolution is limited in
      the first dimension by diffusion of proteins during the long separation period
      and in the second dimension by the combination of a long fraction-transfer time
      and short separation period.

PMID- 15472977
TI  - Multiple sample amplification and genotyping integrated on a single electronic
      microarray.
AB  - We report a novel method that allows simultaneous in situ amplification and then
      genotyping of single nucleotide polymorphism (SNP) for multiple samples on a
      single electronic microarray. The locus coding for one of the common inherited
      thrombosis risk factors, Factor V Leiden (FVL), was chosen as a model system for
      SNP analysis. This method combines strand displacement amplification (SDA) with
      electrophoretic movement and concentration of DNA on electronic microarrays to
      provide a single platform for DNA amplification and analysis. The method
      includes: electronic anchoring of allele-specific SDA amplifiable primers (APs)
      and a nonamplifiable primer (NAP) to different electrodes, electronic
      hybridization of genomic DNA from different samples to those primers, in situ
      amplification of target DNA, and genotyping of FVL. Compared to previous anchored
      SDA methods, the addition of a NAP improves detection signals by at least 20
      fold. The sensitivity of this method is dependent on the amplification time.
      Using this method, nine different genomic DNA samples with known FVL genotypes
      were amplified and correctly genotyped on a single electronic microarray without
      any contamination between samples. The present method could streamline
      development of nucleic acid-based assays in applications of molecular diagnostic,
      point-of-care testing, and forensic detection, which often require the capability
      to analyze multiple samples efficiently.

PMID- 15472978
TI  - Streaming current measurements in zirconia-coated capillaries.
AB  - The electroosmotic flow created in zirconia-modified capillaries has been
      previously investigated. In this paper, we compared the electroosmotic data set
      with streaming current measurements and we related all these data through zeta
      potential. Streaming current measurements give an excellent indication on the
      direction and the value of the electroosmotic mobility of an
      electrolyte/capillary system for a large set of experimental conditions: 2 < pH <
      12, 0 < ACN < 80 %, 10(-4) M < [SO(2- )4 ] < 4 x 10(-2) M. A good correlation
      between zeta-potential from streaming current measurements and zeta-potential
      from electroosmotic mobility measurements was observed (r2 = 0.95). However, the
      values obtained from streaming current were always slightly lower than the one
      calculated from electroosmotic mobility (slope = 0.86, sigma = 0.06). In zirconia
      coated capillaries the zeta-potential can be tuned from -50 to +100 mV depending
      on the composition of the electrolyte.

PMID- 15472979
TI  - Changes in mobile phase ion distribution when combining pressurized flow and
      electric field.
AB  - The distribution of ions in a capillary with both pressurized flow and an
      electric field has been studied. We have earlier reported that the overall
      concentration of ions increase in a capillary with high electric field and a
      pressurized flow. Now we describe how the ions are distributed in the capillary
      both along the capillary length and in the radial direction as a result of the
      parabolic flow profile. We have combined current measurements with finite element
      techniques in order to get better understanding of the system. We have found that
      the concentration of the ions that because of the electric mobility moves towards
      the flow primarily increases at the beginning of the electric field and close to
      the capillary wall. In view of the results we have proposed an alterative
      explanation of earlier published results concerning voltage-induced variation in
      capacity factors.

PMID- 15472980
TI  - Eigenmobilities in background electrolytes for capillary zone electrophoresis:
      III. Linear theory of electromigration.
AB  - A mathematical model of capillary zone electrophoresis (CZE) based on the
      conception of eigenmobilities, which are the eigenvalues of a matrix M tied to
      the linearized governing equations is presented. The model considers CZE systems,
      where constituents, either analytes or components of the background electrolyte
      (BGE), are weak electrolytes--acids, bases, or ampholytes. There is no
      restriction on the number of components nor on the valence of the constituents
      nor on pH of the BGE. An electrophoretic system with N constituents has N
      eigenmobilities. In most BGEs one or two eigenmobilities are very close to zero
      so their corresponding eigenzones move very slowly. However, there are BGEs where
      no eigenmobility is close to zero. The mathematical model further provides: the
      transfer ratio, the molar conductivity detection response, and the relative
      velocity slope. This allows the assessment of the indirect detection,
      conductivity detection and peak broadening (distortion) due to electromigration
      dispersion. Also, we present a spectral decomposition of the matrix M to matrices
      allowing the assessment of the amplitudes of system eigenpeaks (system peaks).
      Our model predicted the existence of BGEs having no stationary injection zone (or
      water zone, gap, peak, dip). A common practice of using the injection zone as a
      marker of the electroosmotic flow must fail in such electrolytes.

PMID- 15472981
TI  - Eigenmobilities in background electrolytes for capillary zone electrophoresis:
      IV. Computer program PeakMaster.
AB  - We are introducing a computer implementation of the mathematical model of zone
      electrophoresis (CZE) described in Stedry, M., Jaros, M., Hruska, V., Gas, B.,
      Electrophoresis 2004, 25, 3071-3079 program PeakMaster. The computer model
      calculates eigenmobilities, which are the eigenvalues of the matrix tied to the
      linearized continuity equations, and which are responsible for the presence of
      system eigenzones (system zones, system peaks). The model also calculates other
      parameters of the background electrolyte (BGE)-pH, conductivity, buffer capacity,
      ionic strength, etc., and parameters of the separated analytes--effective
      mobility, transfer ratio, molar conductivity detection response, and relative
      velocity slope. This allows the assessment of the indirect detection,
      conductivity detection and peak broadening (peak distortion) due to
      electromigration dispersion. The computer model requires the input of the BGE
      composition, the list of analytes to be separated, and the system instrumental
      configuration. The output parameters of the model are directly comparable with
      experiments; the model also simulates electropherograms in a user-friendly way.
      We demonstrate a successful application of PeakMaster for inspection of BGEs
      having no stationary injection zone.

PMID- 15472986
TI  - Differentiation of sulfate and phosphate by H/D exchange mass spectrometry:
      application to isoflavone.
AB  - Often phosphorylation or sulfation is an important step which occurs in the
      signal transduction and cascade of metabolic pathways. Some natural products and
      metabolites contain one or more sulfate or phosphate groups. Isoflavone sulfate
      has been identified from high-resolution mass spectrometry (HRMS) and enzymatic
      digestion by sulfatase. We previously reported the new water-soluble isoflavone
      analogs, daidzein 7-O-phosphate and genistein 7-O-phosphate, which were
      surprisingly hydrolyzed by sulfatase. In this previous study, we could not
      determine the phosphate from the results of HRMS and enzymatic digestion, that
      is, HRMS and enzymatic digestion did not provide clear evidence. In this case, we
      drew conclusions from NMR analysis. HRMS has been ineffective with a regular fast
      atom bombardment (FAB) mass spectrometer to distinguish between phosphate and
      sulfate since the mass difference is only 0.009 mass units. There was, however,
      no conventional method of microanalysis to distinguish phosphate from sulfate
      owing to the same nominal mass. It is still very difficult to determine by
      negative FABMS [--O--P(==O)(OH)(2)] = 80 and [--O--S(==O)(2)OH] = 80. In this
      paper, we report a method to distinguish between these groups by using a popular
      low-resolution mass instrument; thus, phosphate and sulfate were measured by H/D
      exchange mass spectrometry at the picomole level to differentiate [--O-
      P(==O)(OD)(2)] = 82 and [--O--S(==O)(2)OD] = 81, respectively. This method is
      applicable not only to the isoflavone, but also to other phospho and sulfo
      compounds.

PMID- 15472987
TI  - Assembly of an oxo-zirconium(IV) cluster in a protein cleft.

PMID- 15472988
TI  - Fourier transform ion cyclotron resonance study of the gas-phase basicity of N
      nitrosodimethylamine.

PMID- 15472989
TI  - High-voltage-activated calcium channels in Muller cells acutely isolated from
      tiger salamander retina.
AB  - Muller cells mediate retinal function by stabilizing the ionic environment and
      signal glial network activity via calcium waves. Using whole-cell patch clamp
      recording, we describe a high-voltage-activated, slowly inactivating Ca channel
      current in isolated salamander Muller cells that has unusual pharmacological
      properties. The Ca channel current has an activation midpoint of approximately -8
      mV and an inactivation midpoint of approximately -26 mV in 10 mM Ba2+. The time
      constant for inactivation is approximately 380 ms at potentials positive to zero.
      The current is blocked by Cd2+ with an EC50 of <100 nM. nisoldipine (10 microM)
      blocks approximately 50%, while nifedipine (1 microM), diltiazem (20 microM), and
      verapamil (50 microM) each block one-third of the current. In contrast to its
      typical actions, BayK 8644 blocks the current by approximately 25%. Blockers of
      other Ca channel subtypes were also tested: omega-agatoxin IVA (200 nM) blocked
      only 13% of the Ca channel current, while omega-conotoxin GVIA (1 microM) blocked
      84% of the current. Immnohistochemistry supported the presence of alpha1A,
      alpha1B, alpha1C, and alpha1D Ca channel subunits. Mapping of dihydropyridine
      binding sites with DM-BODIPY revealed a distribution of channels over the entire
      membrane of the Muller cell with a higher density at the apical region. Overall,
      these observations suggest either the presence of a mix of L- and N-type Ca
      channels or a single, unconventional HVA Ca channel subtype sharing L- and N-type
      Ca channel characteristics.

PMID- 15472990
TI  - Investigation into factors affecting precision in ion trap mass spectrometry
      using different scan directions and axial modulation potential amplitudes.
AB  - Electrospray ionization mass spectra obtained from different scan directions are
      observed to be dependent on the axial modulation potential amplitudes used for
      resonant ejection and on the positive deviation caused by higher even-multipole
      fields present in most commercial ion traps. The axial modulation voltage
      influences the dissociation of ions during resonant ejection and the observed
      mass shifts. The higher even-multipole fields in commercial ion traps are known
      to influence resonant ejection from the ion trap and can cause a loss in mass
      resolution for peaks in reverse scan mass spectra compared with that obtained by
      the forward scan. However, along with the dissociation of ions during resonant
      ejection causing a loss in resolution, the possibility of resolving an isotopic
      distribution is also shown to be influenced by the mass shifts caused by the
      space charge. These mass shifts differ depending on the scan direction employed.
      A significant loss in resolution can also result from resonant ejection using non
      optimal axial modulation voltages. We also present results showing the ejection
      of ions at betaz = 1/2 using the reverse scan mode without the axial modulation
      voltage. Ion ejection at betaz = 1/2 is uncommon in commercial (stretched ion
      traps) with the conventional analytical scan without the use of a frequency of
      the axial modulation voltage corresponding to this non-linear resonance.

PMID- 15472991
TI  - The cytokine IL-1beta transiently enhances P2X7 receptor expression and function
      in human astrocytes.
AB  - Extracellular nucleotide di- and triphosphates such as ATP and ADP mediate their
      effects through purinergic P2 receptors belonging to either the metabotropic P2Y
      or the ionotropic P2X receptor family. The P2X7R is a unique member of the P2X
      family, which forms a pore in response to ligand stimulation, regulating cell
      permeability, cytokine release, and/or apoptosis. This receptor is also unique in
      that its affinity for the ligand benzoyl-benzoyl ATP (BzATP) is at least 10-fold
      greater than that of ATP. Primary human fetal astrocytes in culture express low
      levels of P2X7R mRNA and protein, and BzATP induces only a slight influx in
      intracellular calcium [Ca2+]i, with little demonstrable effect on gene expression
      or pore formation in these cells. We now show that, following treatment with the
      proinflammatory cytokine IL-1beta, BzATP induces a robust rise in [Ca2+]i with
      agonist and antagonist profiles indicative of the P2X7R. IL-1beta also induced
      the formation of membrane pores as evidenced by the uptake of YO-PRO-1 (375 Da).
      Quantitative real-time PCR demonstrated transient upregulation of P2X7R mRNA in
      IL-1beta-treated cells, while FACS analysis indicated a similar upregulation of
      P2X7R protein at the cell membrane. In multiple sclerosis lesions,
      immunoreactivity for the P2X7R was demonstrated on reactive astrocytes in autopsy
      brain tissues. In turn, P2X7R stimulation increased the production of IL-1
      induced nitric oxide synthase activity by astrocytes in culture. These studies
      suggest that signaling via the P2X7R may modulate the astrocytic response to
      inflammation in the human central nervous system.

PMID- 15472992
TI  - Number of oligodendrocyte progenitors recruited to the lesioned spinal cord is
      modulated by the levels of the cell cycle regulatory protein p27Kip-1.
AB  - Remyelination is a critical step for recovery of function after demyelination and
      defines the ability to generate new myelin. This repair process is dependent on
      the presence of resident oligodendrocyte progenitors (OLPs) that have been shown
      to remyelinate axons after demyelination. We have previously shown that the
      levels of the cell cycle inhibitor p27Kip-1 modulate the number of neonatal
      cortical OLPs. We now asked whether this cell cycle molecule plays also a role in
      regulating the number of adult OLP in the spinal cord after demyelination induced
      by lysolecithin injection. The proliferative response of OLP in the spinal cord
      of injected wild-type (wt) and p27Kip-1 null mice was evaluated 3 days after
      lesion. In vivo labeling with bromodeoxyuridine (BrdU) was used to identify cells
      in S phase. Double immunofluorescence for the OLP marker NG2, and for BrdU was
      used to count the number of proliferating progenitors. Consistent with a role of
      p27Kip-1 in regulating the number of adult OLP in the injured spinal cord, a
      larger number of proliferating OLPs was observed in p27Kip-1null mice compared
      with wild-type controls. These cells were able to differentiate as assessed by
      the presence of MBP+ cells in the spinal cord 14 days after injury. We conclude
      that the cellular levels of the cell cycle inhibitor p27Kip-1 modulate the repair
      response of OLPs to injury in the adult spinal cord.

PMID- 15472993
TI  - Partial trisomy of chromosome 10(q22-q24) due to maternal insertional
      translocation (15;10).
AB  - Interchromosomal insertional translocations are rare chromosome rearrangements
      with an incidence of about 1:80,000 live births. We report on the clinical and
      cytogenetic findings of a newborn baby with partial trisomy 10q22-10q24 due to a
      maternal insertional translocation 15;10. Partial trisomy of the long arm of
      chromosome 10 is a distinctive chromosome aberration characterized by prenatal
      onset growth retardation and craniofacial, skeletal, and other somatic anomalies.
      Most cases are unbalanced products from reciprocal chromosome translocations, and
      insertional translocations are rarely involved. The proband was initially
      referred because of severe intrauterine growth retardation, and fluorescence in
      situ hybridization (FISH) using painting probes confirmed the maternal balanced
      (15;10) insertion.

PMID- 15472994
TI  - IL-1-regulated responses in astrocytes: relevance to injury and recovery.
AB  - In the central nervous system (CNS), the cellular processes of astrocytes make
      intimate contact with essentially all areas of the brain. They have also been
      shown to be functionally coupled to neurons, oligodendrocytes, and other
      astrocytes via both contact-dependent and non-contact-dependent pathways. These
      observations have led to the suggestion that a major function of astrocytes in
      the CNS is to maintain the homeostatic environment, thus promoting the proper
      functioning of the neuronal network. Inflammation in the CNS disrupts this
      process either transiently or permanently and, as such, is thought to be tightly
      regulated by both astrocytes and microglia. The remarkable role that single
      cytokines, such as TNF and IL-1, may play in this process has now been well
      accepted, but the extent of the reprogramming of the transcriptional machinery
      initiated by these factors remains to be fully appreciated. With the advent of
      microarray technology, a more comprehensive analysis of this process is now
      available. In this report we review data obtained with this technology to provide
      an overview of the extent of changes induced in astrocytes by the cytokine IL-1.

PMID- 15472995
TI  - Clinical report of congenital lymphatic malformations and partial gigantism of
      the hands associated with a heterogeneous karyotype.

PMID- 15472996
TI  - Congenital mydriasis, patent ductus arteriosus, and congenital cystic lung
      disease: new syndromic spectrum?

PMID- 15472997
TI  - Intelligence in individuals with a neurofibromatosis type 1 microdeletion.

PMID- 15472998
TI  - Re: Down syndrome and folic acid deficiency.

PMID- 15472999
TI  - Determination of arginine and asymmetric dimethylarginine (ADMA) in human plasma
      by liquid chromatography/mass spectrometry with the isotope dilution technique.
AB  - Arginine (ARG) is a substrate for endogenous nitric oxide (NO) production whereas
      its metabolite, asymmetric dimethylarginine (ADMA), acts as an inhibitor.
      Sufficient NO production is essential for cardiovascular key functions, thus
      elevated concentration levels of ADMA are related to a range of cardiovascular
      diseases. Owing to the lack of reliable methods for the measurement of ARG and
      ADMA in human plasma, concentration values determined with these methods can
      differ considerably. We present here a simple and very robust liquid
      chromatographic/mass spectrometric method for the determination of ARG and ADMA
      utilizing isotope-labeled internal standards. Sample preparation requires only
      protein precipitation; the analytes were derivatized with o-phthalaldehyde
      mercaptoethanol and separated on a reversed-phase C(18) column with gradient
      elution. The analytes were detected with an electrospray ionization ion trap
      instrument working in the full-scan single mass spectrometry mode. Concentration
      values obtained with this method for healthy controls were ARG = 63.9 +/- 23.9
      microM and ADMA = 0.355 +/- 0.066 microM, with a normal range for ADMA from 0.225
      to 0.485 microM. The corresponding values for end-stage chronic renal failure
      patients are ARG = 48.1 +/- 18.5 microM, p < 0.01 and ADMA = 0.673 +/- 0.134 M, p
      < 0.001.

PMID- 15473001
TI  - Glutathione S-transferase M1, T1 and P1 genetic polymorphisms, cigarette smoking
      and gastric cancer risk.
AB  - Glutathione S-transferases (GSTs) belong to a superfamily of detoxification
      enzymes that provide critical defences against a large variety of chemical
      carcinogens and environmental toxicants. GSTs are present in most epithelial
      tissues of the human gastrointestinal tract. We investigated associations between
      genetic variability in specific GST genes (GSTM1, GSTT1 and GSTP1), the
      interaction with cigarette smoking and susceptibility to gastric cancer. The
      GSTM1, GSTT1 and GSTP1 polymorphisms were determined using real-time polymerase
      chain reaction (PCR) and fluorescence resonance energy transfer with Light Cycler
      Instrument. The study included 70 patients with gastric cancer and 204 controls.
      Associations between specific genotypes and the development of gastric cancer
      were examined by use of logistic regression to calculate odds ratios (OR) and 95%
      confidence intervals (CI). The GSTM1 homozygous null genotype was associated with
      an increased risk of developing gastric cancer (OR = 1.73; 95% CI = 1.10-3.04).
      GSTT1 homozygous null genotype and GSTP1 genotypes were not associated with the
      risk of gastric cancer. Also there was no difference between cases and controls
      in the frequency of val-105 and ile-105 alleles (p = 0.07). After grouping
      according to smoking status, GSTM1 null genotype was associated with an increased
      gastric cancer risk for smokers (OR = 2.15; 95% CI, 1.02-4.52). There were no
      significant differences in the distributions of any of the other GST gene
      combinations. Our findings suggest that the GSTM1 null genotype may be associated
      with an increased susceptibility to gastric cancer.

PMID- 15473002
TI  - Direct injection of solid-phase extraction eluents onto silica columns for the
      analysis of polar compounds isoniazid and cetirizine in plasma using hydrophilic
      interaction chromatography with tandem mass spectrometry.
AB  - Isoniazid and cetirizine do not retain well on reversed-phase columns due to
      their high polarity. Silica columns, when operated under hydrophilic interaction
      conditions, do provide excellent retention of these compounds. We have developed
      simple and proof of concept analytical methods for the analysis of isoniazid and
      cetirizine in animal and human plasma, respectively. Both methods employed the
      approach of direct injection of solid-phase extraction (SPE) organic eluents onto
      silica columns for analysis, thus eliminating evaporation and reconstitution
      steps that are typically needed for reversed-phase liquid chromatographic
      analysis. Isoniazid was extracted from animal plasma samples using a Waters Oasis
      HLB 96-well plate and then eluted with acetonitrile, while cetirizine was
      extracted from human plasma with a Waters MCX mu-Elute plate and then eluted with
      acetonitrile containing 5% concentrated ammonium hydroxide. The direct injection
      of the SPE eluent onto the analytical column was necessary since significant loss
      of isoniazid was found during the evaporation and reconstitution steps. The
      method for isoniazid also enabled ultra-fast analysis due to the relatively low
      back-pressure exhibited by silica columns even under high flow conditions. Both
      methods show good linearity, accuracy and precision covering the range of 10-2000
      ng/mL of isoniazid, and 1-1000 ng/mL of cetirizine in plasma. Substantial time
      savings were realized as a result of both the elimination of the evaporation and
      reconstitution steps and the fast chromatographic analysis.

PMID- 15473003
TI  - A novel link between a rab GTPase and Rvs proteins: the yeast amphiphysin
      homologues.
AB  - The BAR proteins are a well-conserved family of proteins including Rvsp in yeast,
      amphiphysins and Bin proteins in mammals. In yeast, as in mammals, BAR proteins
      are known to be implicated in vesicular traffic. The Gyp5p (Ypl249p) and Ymr192p
      proteins interact in two-hybrid tests with both Rvs161p and Rvs167p. Gyp5p is a
      Ypt/Rab-specific GAP and Ymr192p is highly similar to Gyp5p. To specify the
      interaction between Rvsp and Gyp5p, we used two-hybrid tests to determine the
      domains necessary for these interactions. The specific SH3 domain of Rvs167p
      interacted with the N-terminal domain of Gyp5p. Moreover, Gyp5p could form a
      homodimer. Fus2 protein is a specific partner of Rvs161p in two-hybrid tests. To
      characterize the functional relationships between these five proteins, we have
      studied cellular phenotypes in single, double and triple mutant strains for which
      rvs mutants present defects, such as polarity, cell fusion and meiosis.
      Phenotypic analysis showed that Gyp5p, Ymr192p and Fus2p were involved in bipolar
      budding pattern and in meiosis. Specific epistasis or suppressive phenomena were
      found between the five mutations. Finally, The Gyp5p-GFP fusion protein was
      localized at the bud tip during apical growth and at the mother-bud neck during
      cytokinesis. Moreover, Rvs167p and Rvs161p were shown to be essential for the
      correct localization of Gyp5p. Altogether, these data support the hypothesis that
      both Rvsp proteins act in vesicular traffic through physical and functional
      interactions with Ypt/Rab regulators.

PMID- 15473004
TI  - A review of HIV-1 Tat protein biological effects.
AB  - The authors have reviewed some biological properties of HIV-1 Tat protein, and
      have also reported some personal data. This viral regulatory protein is endowed
      with multifunctional activities, acting as an endogenous factor in the infected
      cells and exogenously, on those uninfected. In particular, Tat-induced
      proliferation and differentiation of HIV target cells which promotes viral
      infection, is discussed in this review. However, exogenous Tat protein can
      sometimes also produce, directly or indirectly, damaging effects in different
      organs and host systems, such as myocardium, kidney, liver and central nervous
      system (CNS). For example some data also demonstrate an increase in the apoptotic
      index induced by Tat at various levels, including the immune system. The
      effective role of HIV-1 Tat protein in promoting viral replication and its high
      immunogenicity suggest useful employment of this protein for therapeutic or
      preventive vaccine preparations.

PMID- 15473005
TI  - Diabetes-induced decrease in rat brain microsomal Ca2+-ATPase activity.
AB  - The Ca(2+)-ATPase activity of rat brain microsomes was studied in streptozotocin
      (STZ)-induced diabetes. Male rats, 200-250 g, were rendered diabetic by injection
      of STZ (45 mg kg(-1) body weight) via the teil vein. Brain tissues were collected
      at 1, 4 and 10 weeks after diabetes was induced for determination of Ca(2+)
      ATPase activity, lipid peroxidation and tissue calcium levels. Diabetic rats had
      significantly elevated blood glucose levels compared to controls. Blood glucose
      levels were 92.92 +/- 1.22 mg dl(-1) (mean +/- SEM) for the control group, 362.50
      +/- 9.61 mg dl(-1) at 1 week and >500 mg dl(-1) at 4, 8 and 10 weeks for the
      diabetics. Enzyme activities were significantly decreased at 1, 4, 8 and 10 weeks
      of diabetes relative to the control group (p < 0.001). Ca(2+)-ATPase activity was
      0.084 +/- 0.008 U l(-1), 0.029 +/- 0.005 U l(-1), 0.029 +/- 0.006 U l(-1), 0.033
      +/- 0.003 U l(-1) and 0.058 +/- 0.006 U l(-1) (mean +/- SEM) at control, 1, 4, 8
      and 10 week of diabetes respectively. The change in calcium levels in diabetic
      rat brain at 8 and 10 weeks of diabetes was significantly higher than that of the
      control group (p < 0.05). On the other hand lipid peroxidation measured as TBARS
      (thiobarbituric acid reactive substances) was significantly higher at 8 and 10
      weeks of diabetes (p < 0.05). The increase in lipid peroxidation observed in
      diabetic rat brain may be partly responsible for the decrease in calcium ATPase
      activity.

PMID- 15473006
TI  - Characterization and modulation by drugs of sheep liver microsomal flavin
      monooxygenase activity.
AB  - The flavin monooxygenases (FMO) catalyse the NADPH and oxygen-dependent oxidation
      of a wide range of nucleophilic nitrogen-, sulfur-, phosphorus-, and selenium
      heteroatom-containing chemicals, drugs, and agricultural agents. In the present
      study, sheep liver microsomal FMO activity was determined by measuring the S
      oxidation rate of methimazole and the average specific activity obtained from
      different microsomal preparations was found to be 3.8 +/- 1.5 nmol methimazole
      oxidized min(-1) mg(-1) microsomal protein (mean +/- SE, n = 7). The presence of
      0.1% Triton X-100 in the reaction mixture caused an increase of specific sheep
      liver microsomal FMO activity towards methimazole to 6.1 +/- 1.4 nmol methimazole
      oxidized min(-1) mg(-1) microsomal protein (mean +/- SE, n = 6). Metabolism of
      imipramine and chlorpromazine was measured by following the oxidation of cofactor
      NADPH spectrophotometrically at 340 nm. Sheep liver microsomal FMO activity
      towards imipramine and chlorpromazine was found to be 10.7 and 12.3 nmol NADPH
      oxidized min(-1) mg(-1) microsomal protein, respectively. Characterization of
      sheep liver enzyme was carried out using methimazole as substrate and the maximum
      FMO enzyme activity was detected at 37 degrees C and at pH 8.0. The apparent K(m)
      value of sheep liver microsomal FMO for methimazole was 0.118 mM. Effects of the
      detergents Triton X-100, Cholate, and Emulgen 913, on FMO activity were
      determined and FMO activity was found to increase with the addition of detergents
      to the reaction medium. Sheep liver microsomal FMO-catalysed methimazole
      oxidation was inhibited by imipramine and chlorpromazine when these drugs were
      used at high concentrations. Western blot-immunochemical analysis revealed the
      presence of FMO3 in sheep liver microsomes.

PMID- 15473008
TI  - Scalable fine-grained parallelization of plane-wave-based ab initio molecular
      dynamics for large supercomputers.
AB  - Many systems of great importance in material science, chemistry, solid-state
      physics, and biophysics require forces generated from an electronic structure
      calculation, as opposed to an empirically derived force law to describe their
      properties adequately. The use of such forces as input to Newton's equations of
      motion forms the basis of the ab initio molecular dynamics method, which is able
      to treat the dynamics of chemical bond-breaking and -forming events. However, a
      very large number of electronic structure calculations must be performed to
      compute an ab initio molecular dynamics trajectory, making the efficiency as well
      as the accuracy of the electronic structure representation critical issues. One
      efficient and accurate electronic structure method is the generalized gradient
      approximation to the Kohn-Sham density functional theory implemented using a
      plane-wave basis set and atomic pseudopotentials. The marriage of the gradient
      corrected density functional approach with molecular dynamics, as pioneered by
      Car and Parrinello (R. Car and M. Parrinello, Phys Rev Lett 1985, 55, 2471), has
      been demonstrated to be capable of elucidating the atomic scale structure and
      dynamics underlying many complex systems at finite temperature. However, despite
      the relative efficiency of this approach, it has not been possible to obtain
      parallel scaling of the technique beyond several hundred processors on moderately
      sized systems using standard approaches. Consequently, the time scales that can
      be accessed and the degree of phase space sampling are severely limited. To take
      advantage of next generation computer platforms with thousands of processors such
      as IBM's BlueGene, a novel scalable parallelization strategy for Car-Parrinello
      molecular dynamics is developed using the concept of processor virtualization as
      embodied by the Charm++ parallel programming system. Charm++ allows the diverse
      elements of a Car-Parrinello molecular dynamics calculation to be interleaved
      with low latency such that unprecedented scaling is achieved. As a benchmark, a
      system of 32 water molecules, a common system size employed in the study of the
      aqueous solvation and chemistry of small molecules, is shown to scale on more
      than 1500 processors, which is impossible to achieve using standard approaches.
      This degree of parallel scaling is expected to open new opportunities for
      scientific inquiry.

PMID- 15473007
TI  - Ethanolic leaf extract of neem (Azadirachta indica) inhibits buccal pouch
      carcinogenesis in hamsters.
AB  - We evaluated the chemopreventive effects of ethanolic neem leaf extract in the
      initiation and post-initiation phases of 7,12-dimethylbenz[a]anthracene (DMBA)
      induced hamster buccal pouch (HBP) carcinogenesis. The frequency of bone marrow
      micronuclei as well as the concentrations of lipid peroxides, ratio of reduced to
      oxidized glutathione (GSH/GSSG), and the activities of the GSH-dependent enzymes
      glutathione peroxidase (GPx) and glutathione-S-transferase (GST) in the buccal
      pouch, liver and erythrocytes were used as biomarkers of chemoprevention. All the
      hamsters painted with DMBA alone for 14 weeks developed buccal pouch carcinomas
      that showed diminished lipid peroxidation and enhanced antioxidant status
      associated with increased frequencies of bone marrow micronuclei. In the liver
      and erythrocytes of tumour-bearing animals, enhanced lipid peroxidation was
      accompanied by compromised antioxidant defences. Administration of ethanolic neem
      leaf extract effectively suppressed DMBA-induced HBP carcinogenesis as revealed
      by the absence of tumours in the initiation phase and reduced tumour incidence in
      the post-initiation phase. In addition, ethanolic neem leaf extract modulated
      lipid peroxidation and enhanced antioxidant status in the pouch, liver and
      erythrocytes and reduced the incidence of bone marrow micronuclei. The results of
      the present study, demonstrate that ethanolic neem leaf extract inhibits the
      development of DMBA-induced HBP tumours by protecting against oxidative stress.

PMID- 15473009
TI  - Theoretical studies of structures and stabilities of a new odd-numbered fullerene
      dimer: C141.
AB  - The possible isomers of a newly synthesized C(141) molecule are calculated using
      MNDO, AM1, PM3, B3LYP/3-21G, and B3LYP/6-31G(d) methods. The geometry
      optimizations showed that the isomer 8-8 has the lowest total energy in all 64
      possible structures of C(141). Unlike those of C(130), C(140), etc., the C(141) 8
      8 shows a new structure: two C(70) side cages open [6.6] ring junctions located
      at the equator (instead of cap) area to create new chemical bonds for the bridge
      atom. Theoretical measurements of the average length of the long and short axes
      of C(70) side cages in the C(141) molecule reveal that when two C(70) cages are
      connected with each other at the equators, their geometric shapes become more
      spherical compared with the pristine C(70); this leads to a reduction of the
      molecular polarizability. Analysis of the local and global strain indicates that
      the global strain of C(70) monomer in the C(141) 8-8 is greatly reduced compared
      to the pristine C(70). The stable C(70) derivatives that are formed with reacted
      C-C bonds in the equator area may put new insights into fullerene chemistry, in
      particular, for C(70) to react with a large molecule. The results are discussed
      together with the experimental data.

PMID- 15473010
TI  - Efficiency of the algorithms for the calculation of Slater molecular integrals in
      polyatomic molecules.
AB  - The performances of the algorithms employed in a previously reported program for
      the calculation of integrals with Slater-type orbitals are examined. The
      integrals are classified in types and the efficiency (in terms of the ratio
      accuracy/cost) of the algorithm selected for each type is analyzed. These
      algorithms yield all the one- and two-center integrals (both one- and two
      electron) with an accuracy of at least 12 decimal places and an average
      computational time of very few microseconds per integral. The algorithms for
      three- and four-center electron repulsion integrals, based on the discrete Gauss
      transform, have a computational cost that depends on the local symmetry of the
      molecule and the accuracy of the integrals, standard efficiency being in the
      range of eight decimal places in hundreds of microseconds.

PMID- 15473011
TI  - A hybrid method of molecular dynamics and harmonic dynamics for docking of
      flexible ligand to flexible receptor.
AB  - We have developed a new docking method to consider receptor flexibility, a hybrid
      method of molecular dynamics and harmonic dynamics. The global motions of the
      whole receptor were approximately introduced into those of the receptor in the
      docking simulation as harmonic dynamics. On the other hand, the local flexibility
      of the side chains was also considered by conventional molecular dynamics. We
      confirmed that this new method can reproduce the fluctuations of the whole
      receptor by making a comparison of the directions and amplitudes of the global
      fluctuations. Then this method was applied to the docking of HIV-1 protease and
      its ligand. As a result, we observed a docking process where the ligand enters
      into the binding pocket well, which implies that this method is effective enough
      to reproduce a molecular complex formation.

PMID- 15473012
TI  - A liquid chromatography-mass spectrometry method for the quantification of both
      etoricoxib and valdecoxib in human plasma.
AB  - A practicable and selective liquid chromatography-mass spectrometry assay for the
      determination of two cyclooxygenase-2 inhibitors, etoricoxib and valdecoxib, in
      human plasma is presented. The analytical technique is based on reversed-phase
      high-performance liquid chromatography (HPLC) coupled to atmospheric pressure
      chemical ionisation (APCI) mass spectrometry (Finnigan Mat LCQ ion trap). Mass
      analysis was performed in the positive ion mode. The ion trap was operated in the
      tandem MS mode (MS2) and the transitions of etoricoxib (m/z 359.2 --> 280.3) and
      valdecoxib (m/z 315.1 --> 235.1) were followed by selected reaction monitoring.
      Retention times of etoricoxib and valdecoxib were 1.05 and 1.08 min,
      respectively. The method was validated over a linear range 10-2500 and 5-1000
      microg/L using the other substrate as internal standard. After validation, the
      method was used to study the pharmacokinetic pro fi le of etoricoxib or
      valdecoxib in a healthy volunteer after administration of a single oral dose
      (valdecoxib, 20 mg; etoricoxib, 90 mg). The presented method was suf fi cient to
      cover more than 90% of the area under the plasma concentration time curve.

PMID- 15473013
TI  - Interaction of surface-active drugs in rabbits.
AB  - The interaction of chlorpromazine and promethazine in vivo has been investigated.
      The drugs were administered to the rabbit orally as a single dose (100 mg of each
      drug) as well as simultaneously with an interval of 15 min. The presence of
      multiple peaks at the separate administration of promethazine and chlorpromazine
      on the one hand, and increase of number of peaks, symbathic character of kinetic
      curves of mentioned drugs and its prolonged appearance in the systemic
      circulation of the blood by simultaneous administration on the other hand, may be
      explained by the intensive presystem metabolism and surface-activity ability of
      these drugs, and by the periodic 'lassitude' of liver for their capture and
      elimination (either presystem or systemic). The micelle formation from these
      drugs in the gastro-intestinal tract and formation of the mixed micelles on
      simultaneous administration were also taken into consideration. Chlorpromazine is
      more strongly captured by the liver at its first pass through it than
      promethazine, from comparison of pharmacokinetics of these drugs administered
      separately. Therefore, chlorpromazine on simultaneous administration occupies the
      sites of the liver which were covered by promethazine at single dose, thereby
      substituting promethazine and promoting its transferral into the systemic blood
      circulation. This results in a large increase in promethazine content in blood,
      additional peaks appear and the presence of promethazine in the blood is
      prolonged. The influence of chlorpromazine on the kinetics of promethazine is
      especially obvious when chlorpromazine enters the organism first and more easily
      occupies those sites in the liver which participate in the capture and
      elimination of both drugs. Concerning influence of promethazine on the kinetics
      of chlorpromazine, promethazine reinforces in some way the ability of liver to
      capture chlorpromazine, thereby intensifying the presystem metabolism of
      chlorpromazine and inhibiting its own metabolism. The analogous effect was
      observed in the study of the influence of promethazine on the kinetics of
      carbamazepine.

PMID- 15473015
TI  - Abstracts of the 55th Annual Meeting of the American Association for the Study of
      Liver Diseases. Boston, Massachusetts, USA, October 29-November 2004.

PMID- 15473016
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 15473017
TI  - Doctors and torture.

PMID- 15473018
TI  - Doctors and torture.

PMID- 15473019
TI  - Doctors and torture.

PMID- 15473020
TI  - Doctors and torture.

PMID- 15473021
TI  - Doctors and torture.

PMID- 15473022
TI  - Doctors and torture.

PMID- 15473023
TI  - Cetuximab in colon cancer.

PMID- 15473024
TI  - Cetuximab in colon cancer.

PMID- 15473025
TI  - Media. New survey enlightens teens on HIV protection.

PMID- 15473027
TI  - Discrimination. Company admits firing skilled worker because he has HIV.

PMID- 15473026
TI  - African-Americans lose faith in United States on HIV/AIDS.

PMID- 15473029
TI  - Testing order remanded for man who groped granddaughters.

PMID- 15473028
TI  - Discrimination. Negligence, bias claim filed by HIV-positive inmate fails.

PMID- 15473030
TI  - Prisons. Study links incarceration and HIV rates in black communities.

PMID- 15473031
TI  - Prisons. More ex-cons use protection after counseling sessions.

PMID- 15473032
TI  - Prisons. Inmate deprived of HIV drugs during lockdown loses suit.

PMID- 15473033
TI  - Exposure. Death-row cells of HIV-positive inmates can be reused.

PMID- 15473034
TI  - Abuse of power. HIV-positive man's claim of sexual battery against boss fails.

PMID- 15473035
TI  - Puerto Rico prisons still plagued by medical deficiencies.

PMID- 15473037
TI  - Disclosure. Anguish claim survives dismissal in HIV exposure case.

PMID- 15473036
TI  - Immigration. Fear of death from HIV insufficient to reopen asylum case.

PMID- 15473038
TI  - Patient misdiagnosed as HIV-positive sues hospital.

PMID- 15473039
TI  - Election. AIDS groups launch absentee ballot drive.

PMID- 15473040
TI  - Disease management. AHF is shining star in troubled HIV management initiative.

PMID- 15473041
TI  - Welcome to Bangkok.

PMID- 15473042
TI  - The X4 files.

PMID- 15473043
TI  - HIV co-receptor drugs on the horizon.

PMID- 15473044
TI  - The presidential campaign health reform proposals.

PMID- 15473045
TI  - CD4 monitoring in resource-limited settings. The state of the art at Bangkok.

PMID- 15473047
TI  - Major medical journals will require registration of clinical trials for
      publication.

PMID- 15473046
TI  - [Distribution of capsular types and antimicrobial susceptibility of Streptococcus
      agalactiae causing infections in Argentina].
AB  - Streptococcus agalactiae is an endogenous bacterium that has emerged in the last
      20 years as an etiological agent in both neonatal and perinatal infections, and
      in immunocompromised patients. The differentiation of the capsular
      polysaccharide, the presence of surface proteins c, X, R, and molecular methods
      allow classification in serotypes and genotypes. This identification is a useful
      tool for epidemiological purposes and virulence studies in this bacterium. The
      objective of this work was to study the serotypes and the antimicrobial
      susceptibility of isolates recovered from invasive diseases in different areas of
      Argentina. In the analyzed sample a fair predominance of Ia and III serotypes was
      recovered, followed by II and IV serotypes. All the isolates were found to be
      sensitive to penicillin. A 6% of resistance to erythromycin and a 4.5% to
      clindamycin were detected. In three of the isolates, constitutive MLS phenotype
      (resistance to macrolides, lincosamins and streptogramins) was founded, while in
      the remaining one, inducible MLS phenotype was detected. These results stress the
      importance of conducting a surveillance of the prevalent serotypes in our country
      with the goal of future prevention of this disease with an effective vaccine. The
      knowledge of the antimicrobial susceptibility profile will be also important to
      obtain therapeutic success in the treatment.

PMID- 15473048
TI  - Study finds hospitalists reduce length of stay and costs.

PMID- 15473049
TI  - Study suggests mammography has low risk of false positive recalls.

PMID- 15473050
TI  - Study shows sharp rise in U.S. hypertension rate.

PMID- 15473051
TI  - Special report: the efficacy of interventions to change physician prescribing
      behavior.

PMID- 15473052
TI  - Study of CNG/diesel dual fuel engine's emissions by means of RBF neural network.
AB  - Great efforts have been made to resolve the serious environmental pollution and
      inevitable declining of energy resources. A review of Chinese fuel reserves and
      engine technology showed that compressed natural gas (CNG)/diesel dual fuel
      engine (DFE) was one of the best solutions for the above problems at present. In
      order to study and improve the emission performance of CNG/diesel DFE, an
      emission model for DFE based on radial basis function (RBF) neural network was
      developed which was a black-box input-output training data model not require
      priori knowledge. The RBF centers and the connected weights could be selected
      automatically according to the distribution of the training data in input-output
      space and the given approximating error. Studies showed that the predicted
      results accorded well with the experimental data over a large range of operating
      conditions from low load to high load. The developed emissions model based on the
      RBF neural network could be used to successfully predict and optimize the
      emissions performance of DFE. And the effect of the DFEmain performance
      parameters, such as rotation speed, load, pilot quantity and injection timing,
      were also predicted by means of this model. In resume, an emission prediction
      model for CNG/diesel DFE based on RBF neural network was built for analyzing the
      effect of the main performance parameters on the CO, NOx, emissions of DFE. The
      predicted results agreed quite well with the traditional emissions model, which
      indicated that the model had certain application value, although it still has
      some limitations, because of its high dependence on the quantity of the
      experimental sample data.

PMID- 15473053
TI  - Common and constrasting areas of activation for abstract and concrete concepts:
      an H2 15O PET study.
AB  - Lesion studies indicate that the lateral and inferior temporal cortex is a
      critical area of semantic memory storage, but little is known about the cortical
      organization of semantics within this area. One proposition has been that
      dominant physical characteristics of objects (structure, motility) are
      determining factors. A positron emission tomography experiment using the H2(15)O
      bolus method was performed to test this hypothesis by contrasting activation for
      concrete and abstract concepts. Unlike previous studies that considered this
      question, the task required explicit word meaning judgments, and blocks of trials
      were designed to be of equal difficulty for the two word classes. The task
      required elderly participants to read aloud the pair of words that was closer in
      meaning (e.g., spade-shovel vs. spade-carpet). Subtraction analyses that compared
      the semantic judgment tasks with a baseline condition indicated that both
      abstract and concrete concepts activated the left lateral temporal cortex. A
      direct comparison of abstract versus concrete scans indicated differences in the
      lateralization of fusiform activation. We conclude that although concreteness
      might be a critical factor in the fusiform cortex, it is not dominant in the
      lateral temporal cortex. A multistudy overview suggests that tasks that focus on
      one concept per trial activate areas posterior to y = -40, whereas those that
      invoke several concepts, as in the present study, activate areas anterior to
      this. Increased processing complexity may proceed in a posterior-anterior
      direction in the lateral temporal cortex.

PMID- 15473054
TI  - Combinatorial model of solute transport in porous media.
AB  - Modeling of solute transport is a key issue in the area of soil physics and
      hydrogeology. The most common approach (the convection-dispersion equation)
      considers an average convection flow rate and Fickian-like dispersion. Here, we
      propose a solute transport model in porous media of continuously expanding scale,
      according to the combinatorics principle. The model supposed actual porous media
      as a combinative body of many basic segments. First, we studied the solute
      transport process in each basic segment body, and then deduced the distribution
      of pore velocity in each basic segment body by difference approximation, finally
      assembled the solute transport process of each basic segment body into one of the
      combinative body. The simulation result coincided with the solute transport
      process observed in test. The model provides useful insight into the solute
      transport process of the non-Fickian dispersion in continuously expanding scale.

PMID- 15473055
TI  - Immunochemical versus guaiac fecal occult blood tests.

PMID- 15473056
TI  - CT colonography ("virtual colonoscopy") for colon cancer screening.

PMID- 15473057
TI  - AAFP patient education handouts.

PMID- 15473058
TI  - [Specific anatomy of the mouth cavity].

PMID- 15473059
TI  - Classification of cystic fibrosis and related disorders.

PMID- 15473060
TI  - Services for adults with cystic fibrosis.

PMID- 15473061
TI  - "Beam me down, Scottie!": Satellite teleconferencing.

PMID- 15473062
TI  - A notch in time.

PMID- 15473063
TI  - Intravitreal injection of vascular endothelial growth factor small interfering
      RNA inhibits growth and leakage in a nonhuman primate, laser-induced model of
      choroidal neovascularization.

PMID- 15473064
TI  - Practical ethics. Habla usted Espanol?

PMID- 15473065
TI  - [Characteristics and detection of sorbitol-fermenting Shiga toxin-producing E.
      Coli 0157:H-].

PMID- 15473066
TI  - Computational approach to systems biology: from fraction to integration and
      beyond.
AB  - Systems biology is an approach to understanding the workings of whole biological
      systems. The various methods used for systems analyses range from experimental to
      computational. In this paper, we describe basic concepts of systems biology,
      modeling challenges that arise from the massively parallel interaction among
      components in biological systems, and what lies beyond integration of modular
      knowledge.

PMID- 15473067
TI  - Agent-based computational modeling of wounded epithelial cell monolayers.
AB  - Computational modeling of biological systems, or in silico biology, is an
      emerging tool for understanding structure and order in biological tissues.
      Computational models of the behavior of epithelial cells in monolayer cell
      culture have been developed and used to predict the healing characteristics of
      scratch wounds made to urothelial cell cultures maintained in low- and
      physiological [Ca2+] environments. Both computational models and in vitro
      experiments demonstrated that in low exogenous [Ca2+], the closure of 500-microm
      scratch wounds was achieved primarily by cell migration into the denuded area.
      The wound healing rate in low (0.09 mM) [Ca2+] was approximately twice as rapid
      as in physiological (2 mM) [Ca2+]. Computational modeling predicted that in cell
      cultures that are actively proliferating, no increase in the fraction of cells in
      the S-phase would be expected, and this conclusion was supported experimentally
      in vitro by bromodeoxyuridine incorporation assay. We have demonstrated that a
      simple rule-based model of cell behavior, incorporating rules relating to contact
      inhibition of proliferation and migration, is sufficient to qualitatively predict
      the calcium-dependent pattern of wound closure observed in vitro. Differences
      between the in vitro and in silico models suggest a role for wound-induced
      signaling events in urothelial cell cultures.

PMID- 15473068
TI  - Towards cooperative frameworks for modeling and integrating biological processes
      knowledge.
AB  - Data organization has become a strategic target for biologists due to the
      increasing volume of genomic data available for them. For this purpose, we need a
      complete knowledge model for representing biological system. In this paper, we
      deal with both processes for the creation and integration of shareable, reusable
      domain models within biology, which is a critical issue. In particular, this work
      introduces a new cooperative development approach for biology ontologies. This
      approach is based on the integration of the ontologies supplied by different
      human experts. Two experiments in biological domains are presented and their
      results discussed.

PMID- 15473069
TI  - Mathematical modeling of complex regulatory networks.
AB  - Cellular regulation comprises overwhelmingly complex interactions between genes
      and proteins that ultimately will only be rendered understandable by employing
      formal approaches. Developing large-scale mathematical models of such systems in
      an efficient and reliable way, however, requires careful evaluation of
      structuring principles for the models, of the description of the system dynamics,
      and of the experimental data basis for adjusting the models to reality. We
      discuss these three aspects of model development using the example of cell cycle
      regulation in yeast and suggest that capturing complex dynamic networks is
      feasible despite incomplete (quantitative) biological knowledge.

PMID- 15473070
TI  - Hunting drug targets by systems-level modeling of gene expression profiles.
AB  - Structural learning of Bayesian networks applied to sets of genome-wide
      expression patterns has been recently discovered as a potentially useful tool for
      the systems-level statistical description of gene interactions. We train and
      analyze Bayesian networks with the goal of inferring biological aspects of gene
      function. Our two-component approach focuses on supporting the drug discovery
      process by identifying genes with central roles for the network operation, which
      could act as drug targets. The first component, referred to as scale-free
      analysis, uses topological measures of the network-related to a high-traffic load
      of genes-as estimators for their functional importance. The second component,
      referred to as generative inverse modeling, is a method of estimating the effect
      of a simulated drug treatment or mutation on the global state of the network, as
      measured in the expression profile. We show for a dataset from acute
      lymphoblastic leukemia patients that both approaches are suitable for finding
      genes with central cellular functions. In addition, generative inverse modeling
      correctly identifies a known oncogene in a purely data-driven way.

PMID- 15473071
TI  - Web-based information retrieval system for the prediction of metabolic pathways.
AB  - Analysis of metabolic pathways is a central topic in understanding the
      relationship between genotype and phenotype. The rapid accumulation of biological
      data provides the possibility of studying metabolic pathways both at the genomic
      and metabolic levels. Our motivation is to develop a conceptual framework and
      computational system that will allow retrieval of metabolic information and
      prediction of metabolic pathways. In this paper, we introduce a metabolic pathway
      prediction framework that extracts metabolic information from biological
      databases via the Internet, and builds metabolic pathways with data sources of
      genes, sequences, enzymes, metabolites, etc. It provides an easy-to-use interface
      to retrieve, display, and manipulate metabolic information. The system has been
      implemented into PathAligner, available at http://bibiserv.techfak.uni-bielefeld.
      de/pathaligner/.

PMID- 15473072
TI  - Modeling and simulation of intracellular dynamics: choosing an appropriate
      framework.
AB  - Systems biology is a reemerging paradigm which, among other things, focuses on
      mathematical modeling and simulation of biochemical reaction networks in
      intracellular processes. For most simulation tools and publications, they are
      usually characterized by either preferring stochastic simulation or rate equation
      models. The use of stochastic simulation is occasionally accompanied with
      arguments against rate equations. Motivated by these arguments, we discuss in
      this paper the relationship between these two forms of representation. Toward
      this end, we provide a novel compact derivation for the stochastic rate constant
      that forms the basis of the popular Gillespie algorithm. Comparing the
      mathematical basis of the two popular conceptual frameworks of generalized mass
      action models and the chemical master equation, we argue that some of the
      arguments that have been put forward are ignoring subtle differences and
      similarities that are important for answering the question in which conceptual
      framework one should investigate intracellular dynamics.

PMID- 15473073
TI  - Evolvable social agents for bacterial systems modeling.
AB  - We present two approaches to the individual-based modeling (IbM) of bacterial
      ecologies and evolution using computational tools. The IbM approach is
      introduced, and its important complementary role to biosystems modeling is
      discussed. A fine-grained model of bacterial evolution is then presented that is
      based on networks of interactivity between computational objects representing
      genes and proteins. This is followed by a coarser grained agent-based model,
      which is designed to explore the evolvability of adaptive behavioral strategies
      in artificial bacteria represented by learning classifier systems. The structure
      and implementation of the two proposed individual-based bacterial models are
      discussed, and some results from simulation experiments are presented,
      illustrating their adaptive properties.

PMID- 15473074
TI  - Dynamic ion channel activation scheduling in patch clamp on a chip.
AB  - In 2002, Fertig et al. made a remarkable invention: the first successful
      demonstration of a patch clamp on a chip--a planar quartz-based biological chip
      that contains up to several hundred ion channels. This patch-clamp chip can be
      used in massively parallel screens for ion channel activity, thereby providing a
      high-throughput screening tool for drug discovery efforts. In this paper, we
      propose computationally efficient dynamic stochastic scheduling algorithms for
      activating individual ion channels in the patch-clamp chip. By formulating the
      ion channel activation scheduling problem as a partially observed Markov decision
      process with a multiarmed bandit structure, near-optimal dynamic scheduling for
      activation of the individual channels is achieved to optimize the information
      gained from the patch-clamp chip. Numerical examples using state-of-the-art
      algorithms developed recently in artificial intelligence and operations research
      are presented to illustrate these dynamic ion channel (macromolecule) activation
      scheduling algorithms.

PMID- 15473075
TI  - Electric fields within cells as a function of membrane resistivity--a model
      study.
AB  - Externally applied electric fields play an important role in many therapeutic
      modalities, but the fields they produce inside cells remain largely unknown. This
      study makes use of a three-dimensional model to determine the electric field that
      exists in the intracellular domain of a 10-microm spherical cell exposed to an
      applied field of 100 V/cm. The transmembrane potential resulting from the applied
      field was also determined and its change was compared to those of the
      intracellular field. The intracellular field increased as the membrane resistance
      decreased over a wide range of values. The results showed that the intracellular
      electric field was about 1.1 mV/cm for Rm of 10,000 omega x cm2, increasing to
      about 111 mV/cm as Rm decreased to 100 omega x cm2. Over this range of Rm the
      transmembrane potential was nearly constant. The transmembrane potential declined
      only as Rm decreased below 1 omega x cm2. The simulation results suggest that
      intracellular electric field depends on Rm in its physiologic range, and may not
      be negligible in understanding some mechanisms of electric field-mediated
      therapies.

PMID- 15473076
TI  - Incidence of childhood leukemia and oil exploitation in the Amazon basin of
      Ecuador.
AB  - To determine whether there was any difference in childhood leukemia incidence
      rates between populations living in the proximity to oil fields and those living
      in areas free from oil exploitation in the Amazon basin of Ecuador, 91 cancer
      cases among children (0-14 years) from the provinces of Sucumbios, Orellana,
      Napo, and Pastaza during the period 1985-2000 were studied. The relative risks
      for all leukemias indicated significantly elevated levels in the youngest age
      group (0-4 years), both genders combined (RR 3.48, 95% CI 1.25-9.67), and in all
      age groups (0-14 years) combined for females (RR 2.60, 95% CI 1.11-6.08) and both
      genders combined (RR 2.56, 95% CI 1.35-4.86). There was no significant difference
      between the two groups in all other cancer sites combined. Study results are
      compatible with a relationship between childhood leukemia incidence and living in
      the proximity of oil fields in the Ecuadorian Amazon.

PMID- 15473077
TI  - Malignant mesothelioma surveillance: a comparison of ICD 10 mortality data with
      SEER incidence data in nine areas of the United States.
AB  - With the implementation in 1999 of ICD-10 death certificate coding in the United
      States, mortality data specific to malignant mesothelioma became readily
      available on a national basis. To evaluate the accuracy and completeness of
      diagnosis and coding for mesothelioma on the death certificate, mortality
      information was compared with incidence data. A mortality/incidence ratio was
      calculated for each of the nine areas covered by the SEER Program, using National
      Vital Statistics mortality data from 1999 and 2000, and the SEER incidence data
      for 1998 and 1999. The mortality/incidence ratio for the two years combined for
      all areas was 0.82. Only two areas (Connecticut and Atlanta) had ratios <80%. The
      overall correlation coefficient between mortality and incidence rates was 0.96.
      Thus, mortality data coded using ICD-10 can be a valid source for mesothelioma
      surveillance and can be instituted without major cost if a national mortality
      statistics program based on ICD-10 is in place, making it feasible even for
      developing countries.

PMID- 15473078
TI  - Glycophorin A is a potential biomarker for the mutagenic effects of pesticides.
AB  - For individuals with multiple exposures to bone marrow mutagens the glycophorin A
      (GPA) assay appears to detect the cumulative genotoxic effects of these
      nonspecific exposures. To determine whether workers exposed to organophosphates
      and/or carbamate pesticides have more GPA variants compared with controls, this
      cross-sectional cohort study examined 67 Latino farm workers, most of whom were
      exposed to organophosphate or carbamate pesticides, and 68 age-, gender-,
      ethnicity-, and education-matched reference subjects. Of the 27 participants who
      completed the questionnaire and had the M/N alleleotype required for the GPA
      assay, the N/N variant frequency was 9.1 x 10(-6) in the ten subjects with more
      than 1,500 cumulative hours of exposure vs 3.8 x 10(-6) in the six referent
      subjects with no known pesticide exposure (p = 0.097). A consistent trend with
      increasing cumulative exposure was found for N/N and O/N allele-loss frequencies
      when exposures were stratified into three groups. Despite the small sample size
      due to the alleleotype restriction, these findings support the hypothesis that
      some pesticides are mutagenic to hematopoietic stem cells.

PMID- 15473079
TI  - Urinary hexane diamine to assess respiratory exposure to hexamethylene
      diisocyanate aerosol: a human inhalation study.
AB  - The use of urinary hexane diamine (HDA) as a biomarker to assess human
      respiratory exposure to hexamethylene diisocyanate (HDI) aerosol was evaluated.
      Twenty-three auto body shop workers were exposed to HDI biuret aerosol for two
      hours using a closed exposure apparatus. HDI exposures were quantified using both
      a direct-reading instrument and a treated-filter method. Urine samples collected
      at baseline, immediately post exposure, and every four to five hours for up to 20
      hours were analyzed for HDA using gas chromatography and mass spectrometry. Mean
      urinary HDA (microg/g creatinine) sharply increased from the baseline value of
      0.7 to 18.1 immediately post exposure and decreased rapidly to 4.7, 1.9 and 1.1,
      respectively, at 4, 9, and 18 hours post exposure. Considerable individual
      variability was found. Urinary HDA can assess acute respiratory exposure to HDI
      aerosol, but may have limited use as a biomarker of exposure in the workplace.

PMID- 15473080
TI  - Pulmonary effects of occupational exposure to Portland cement: a study from
      eastern Saudi Arabia.
AB  - A cross-sectional study was conducted in a randomly selected factory producing
      Portland cement in eastern Saudi Arabia to determine the prevalence of
      respiratory symptoms and diseases and chest x-ray changes consistent with
      pneumoconiosis in the employees. A sample of 150 exposed and 355 unexposed
      employees was selected. A questionnaire about respiratory symptoms was completed
      during an interview. Chest x-rays were read according to the ILO criteria for
      pneumoconiosis. Dust level was determined by the gravimetric method.
      Concentrations of personal respirable dust ranged from 2.13 mg/m3 in the kilns to
      59.52 mg/m3 in the quarry area. Cough and phlegm were found to be related to
      cigarette smoking, while wheezing, shortness of breath, and bronchial asthma were
      related to dust levels. It is recommended that engineering measures be adopted to
      reduce the dust level in this company, together with health monitoring of exposed
      employees.

PMID- 15473081
TI  - Radiologic abnormalities in South African mica millers: a survey of a mica
      milling plant in the Limpopo Province.
AB  - All 73 workers at a South African mica milling plant were surveyed for
      radiographic evidence of abnormalities related to dust exposures at work. Chest x
      rays were taken and questionnaires administered to determine occupational and
      environmental exposure histories. Dust levels to which workers were exposed were
      measured. All but one of 12 airborne inhalable and respirable dust levels were
      below the occupational exposure limits (OEL-RLs) of 10 mg/m3 and 5 mg/m3
      respectively. The mica concentrations were below the OEL-RL of 1 mg/m3 for
      respirable mica. Mean age and service duration of the workers were 45 and 14
      years, respectively. 19 workers (27%) had changes referable to their exposures to
      asbestos, mica, silica, or combinations. Of these, four showed additional
      radiographic changes in keeping with tuberculous lung scarring. Six had evidence
      of lung changes consistent with past tuberculosis alone. Rates of radiologic
      abnormalities were higher in older workers and those with longer service. An
      association between mica and radiologic changes could not be convincingly shown
      because of the nature of the survey and the co-exposure to other mineral dusts.
      Nevertheless, six workers had radiologic changes consistent with pneumoconiosis
      attributable to mica or the combination of mica and silica.

PMID- 15473082
TI  - Health effects of wastewater reuse for agriculture in the suburbs of Asmara city,
      Eritrea.
AB  - The health impact of utilization of raw domestic sewage for vegetable cultivation
      in the suburbs of Asmara, Eritrea, was assessed. Results showed heavy
      contamination of vegetables by fecal coliforms and Giardia cysts as well as other
      pathogenic bacteria such as Shigella and Salmonella. Stool samples from 75
      occupationally exposed farmers revealed that 45% of them were harboring Giardia
      cysts. Dietary intake of raw greens (lettuce, cabbage) grown on the raw sewage
      appears to cause giardiasis, amebiasis, and diarrhea in the farming community as
      well as in the surrounding area. Comparison of hospital data from the affected
      area with data from other areas of Eritrea indicated that agriculture use of
      untreated wastewater was the major cause of the increase in giardiasis and other
      gastrointestinal diseases.

PMID- 15473083
TI  - Organophosphate pesticide exposures of traditional and integrated pest management
      farmers from working air conditions: a case study in Thailand.
AB  - Concentrations of organophosphate pesticides, including chlorpyrifos and methyl
      parathion, were measured in ambient air breathed by farmers in Tambon Bang Rieng,
      Thailand. An exposure assessment and comparison was made between the levels of
      pesticide exposure of traditional and integrated pest management (IPM) farmers.
      Thirty-three air samples were collected during pesticide spraying. Traditional
      farmers were exposed to higher levels of the pesticide(s), with an average
      concentration of 0.19 mg/m3, compared with 0.037 mg/m3 for the IPM farmers. It
      was estimated that a farmer of Tambon Bang Rieng would be exposed to 81-12,261 mg
      of the organophosphate pesticide(s) via inhalation throughout his or her
      lifetime. Moreover, traditional farmers absorbed more of pesticide via inhalation
      than did IPM farmers.

PMID- 15473084
TI  - Genetically modified cotton and farmers' health in China.
AB  - This study provides the first evidence of a direct link between the adoption of a
      genetically modified (GM) crop and improvements in human health. Estimation of
      the impact of Bacillus thuringiensis (Bt) cotton adoption on pesticide use from
      data from a survey of cotton farmers in northern China, 1999-2001, showed that Bt
      cotton adoption reduced pesticide use. Assessment of a health-production function
      showed that predicted pesticide use had a positive impact on poisoning incidence.
      Taken together, these results indicate that the adoption of Bt cotton can
      substantially reduce the risk and the incidence of poisonings.

PMID- 15473085
TI  - Modeling the dietary pesticide exposures of young children.
AB  - A stepped approach was used to assess the exposures of 1 1/2-4 1/2-year-old
      children in the United Kingdom to residues of pesticides (dithiocarbamates;
      phosmet; carbendazim) found in apples and pears. The theoretical possibility that
      the acute reference dose (ARD) was being exceeded for a particular
      pesticide/fruit was tested by applying a combination of maximal variability and
      maximum measured residue relative to an average-body-weight consumer. The actual
      risk was then quantified by stochastically modeling consumption, from dietary
      survey data, with individual body weights, against published residue results for
      2000-2002 and the variability of residue distribution within batches. The
      results, expressed as numbers of children per day likely to ingest more than the
      ARD, were in the range of 10-226.6 children per day, depending upon the pesticide
      and year of sampling. The implications for regulatory action are discussed.

PMID- 15473086
TI  - Fluoride exposure and respiratory symptoms in welders.
AB  - Welders inhale gases and respirable particles. To investigate the relationship
      between fluoride exposure and respiratory symptoms in welders using basic
      electrodes containing calcium fluoride, 63 railroad track welders were
      interviewed. Fluoride was measured in post-shift urine samples. Seventeen welders
      reported respiratory symptoms related to welding fume exposures. Respiratory
      symptoms were somewhat more common with increasing concentrations of fluoride in
      urine. The association between welding fume exposure and respiratory symptoms
      seems related more to fluorides than to other particles among welders using basic
      electrodes.

PMID- 15473087
TI  - Influence of differences in their jobs on cardiovascular risk factors in male
      blue-collar shift workers in their fifties.
AB  - This study examined relationships between different job types of shift work and
      hypertension, obesity, and dyslipidemia. Male blue-collar workers 50-59 years of
      age (n = 210) on the same three-shift schedule in a pulp and paper mill were
      divided into two groups; 118 in paper manufacturing (group 1) and 92 in the
      chemical products section (group 2). Only the frequency of hypertension differed
      significantly (p = 0.012) between the groups, 52.2% (n = 48) in group 2 vs 33.9%
      (n = 40) in group 1. The odds ratio for group 2 in relation to hypertension was
      2.3 (95% CI 1.2-4.2). These results indicate a positive association between job
      type of shift work and hypertension and suggest that different job types of shift
      workers should not be combined when the effects of shift work on blood pressure
      are being examined.

PMID- 15473088
TI  - Occupational health and gorilla conservation in Rwanda.
AB  - The design and implementation of an employee health program for people who work
      with mountain gorillas in Rwanda is described. This program aims to improve
      worker health and to reduce human-to-gorilla transmission of infectious disease.
      The program covered approximately 111 workers, generally healthy men and women 25
      45 years old, including essentially all people in Rwanda who have regular contact
      with gorillas. Initial assessment included a questionnaire, medical examination,
      and local tests. U.S. laboratory facilities were utilized to confirm some results
      and for serologic testing for zoonotic (simian) viruses. Initial interventions
      included STD/HIV prevention health education, tetanus immunization, and
      anthelminthic treatment. Local physicians continue to provide health services,
      including follow-up testing and treatment. Mountain Gorilla Veterinary Project
      (MGVP) veterinarians assist in planning and implementing continuing program
      components in collaboration with local health authorities and the other employing
      organizations.

PMID- 15473089
TI  - Distance learning in occupational health.
AB  - The burden of occupational illnesses and injuries in the developing world is now
      enormous. Local experts in occupational health and safety are needed to address
      the growing worker and environmental health problems brought about by global
      industrial expansion, but such expertise is lacking. The author describes a 15
      week, online, instructor-led course, Principles of Environmental and Occupational
      Health, that was offered to international students over two semesters. She
      suggests the needs that must be determined and recommends collaborative
      development of a real-time, online curriculum to enhance the training of
      professionals in occupational and environmental health.

PMID- 15473090
TI  - U.S. Department of Defense and White House working together to avoid cleanup and
      liability for perchlorate pollution.
AB  - The toxic anti-thyroidic chemical perchlorate, used in rocket fuel, has leached
      from military dumpsites into public drinking water sources, contaminating the
      water at dangerous levels in many states. The Department of Defense and its
      contractors such as Lockheed Martin are using obfuscation to wage a campaign to
      slow or block Environmental Protection Agency regulatory measures that might cost
      them billions of dollars in cleanup and liability. The influence of the DOD over
      the EPA is cause for extreme concern.

PMID- 15473091
TI  - "Hormesis"--an inappropriate extrapolation from the specific to the universal.
AB  - Although it is generally accepted that some chemicals may have beneficial effects
      at low doses, incorporating these effects into risk assessments generally ignores
      well-established factors related to exposure and human susceptibility. The
      authors argue against indiscriminate application of hormesis in assessments of
      chemical risks for regulatory purposes.

PMID- 15473092
TI  - The decline and imminent fall of U.K. governmental occupational health: a tale of
      forgotten lessons and missed opportunities.
AB  - Governmental efforts to monitor and regulate occupational health and safety
      hazards in the United Kingdom have been seriously etiolated by recent
      developments emanating from the HSC and the HSE that gut already-inadequate
      strategies in ways that favor industry prerogatives over workers, and by
      governmental inattention.

PMID- 15473093
TI  - Water fluoridation and the environment: current perspective in the United States.
AB  - Evidence of water fluoridation's effects on plants, animals, and humans is
      considered based on reviews by scientific groups and individual communities,
      including Fort Collins, CO, Port Angeles, WA, and Tacoma-Pierce County, WA. The
      potential for corrosion of pipes and the use of fluoridation chemicals,
      particularly fluorosilicic acid, are considered, as is the debate about whether
      fluoridation increases lead in water, with the conclusion that there is no such
      increase. The arguments of anti-fluoridationists and fluoridation proponents are
      examined with respect to the politics of the issue.

PMID- 15473094
TI  - Ethical commerce with the Third World: roles for the individual and the ILO.

PMID- 15473095
TI  - Health and safety executive inspection of U.K. semiconductor manufacturers.

PMID- 15473096
TI  - Model these best practices to prevent surgical infections.

PMID- 15473097
TI  - Nursing performance measures to assist hospitals in benchmarking.
AB  - Hospitals have a new set of 15 standardized measures they can use to evaluate the
      quality of nursing care their staffs provide and benchmark that performance
      against other institutions.

PMID- 15473098
TI  - Disease registries provide performance boost without big cost.
AB  - There is a fairly simple and low-cost way of computerizing some patient data that
      is having a big payoff for practices in terms of improving performance and
      quality. Disease registries are databases that allow practices to track patients
      with one or more chronic conditions, including diabetes, asthma, and congestive
      heart failure.

PMID- 15473099
TI  - Caregivers can play a vital role in reducing readmissions.
AB  - Hospitals have spent a lot of effort improving the performance of physicians and
      nurses, but they may be overlooking a key member of the health care team--the
      patient's caregiver. Family members that care for patients at home can provide
      valuable information and feedback to health care professionals. Educating and
      training caregivers can increase compliance with discharge plans and prevent
      readmissions. During hospitalizations, caregivers can act as quality monitors,
      alerting staff members to potential costly problems before they happen.

PMID- 15473100
TI  - Predictors of outpatient mental health service use--the role of foster care
      placement change.
AB  - This study examined the relationship between placement change and outpatient
      mental health service use. It is based on (1) conceptual propositions about the
      impact of the foster care living context on mental health service use, and (2)
      empirical knowledge about the adverse consequences of placement change. Results
      of the study, which were based on a cohort of 570 children in foster care in San
      Diego County, suggest an association between placement changes in child welfare
      and use of outpatient mental health services. Specifically, an increase in the
      number of placement changes predicted a greater rate of outpatient mental health
      visits. The study further found that children who experienced behavior-related
      placement changes received more outpatient mental health visits than children who
      experienced placement changes for other reasons. Follow-up analyses of the 144
      children who experienced any behavior-related placement changes further indicated
      that the rate of outpatient mental health service use almost doubled in the 90
      days following the first behavior-related placement change. Findings from this
      study have implications for the practice, policy and research fields in child
      welfare as well as mental health.

PMID- 15473101
TI  - Untangling the web: an approach to analyzing the impacts of individually
      tailored, multicomponent treatment interventions.
AB  - In this paper the use of a maximum individualized change score is proposed as an
      analytic alternative to the more traditional MANOVA and latent variable
      approaches in studies examining the use of individually tailored interventions.
      This strategy offers a number of significant advantages when multiple indicators
      are used to assess a broad array of potential outcomes that might result from
      client-specific treatments. Data on 146 children from a study examining the
      effectiveness of 3 short-term intensive in-home services were used to contrast
      the results of our proposed analytic strategy with those from the MANOVA and
      latent variable approaches. Results indicate that the maximum individualized
      change score approach improves the outcome comparisons among the 3 treatment
      interventions and eliminates some concerns regarding subjectivity that exists
      with procedures such as goal-attainment scaling. A simulation study suggests the
      maximum change score statistics is a nonbiased estimate for assessing between
      group differences in program effectiveness and has more power than MANOVA to
      produce significant differences when smaller program effects exist. Suggestions
      for strengthening this analytic approach as well as examples regarding use of
      this technique in other research contexts are also provided.

PMID- 15473102
TI  - Cost assessment of a school-based mental health screening and treatment program
      in New York City.
AB  - Although school-based mental health screening and treatment programs have been
      proposed as a viable means of reaching youth with unmet mental health needs, no
      previous reports have attempted to comprehensively document the costs of such
      programs. The purposes of this report are (1) to estimate the cost of a school
      based mental health screening and treatment program in a real-world school
      setting, and (2) to outline the methods and procedures that should be employed by
      future investigators to explore the costs of such programs. The program, located
      in a middle school in a low-income, largely Hispanic neighborhood in New York
      City, aimed to screen all students in Grades 6-8 for anxiety, depression, and
      substance use disorders. Most students in need of treatment were referred to the
      school-based treatment program, where social workers offered individual and group
      counseling. Economic evaluation methods and a before/after study design were used
      to assess the costs of the screening and treatment programs for 3 years of
      operation. Costs were estimated from the societal perspective, which includes all
      measurable program costs regardless of who bears the costs, and the school
      perspective, which includes only costs that would be borne directly by a school
      operating these programs. Data primarily came from administrative records and
      staff interviews. The total cost ranged from 106,125 dollars to 172,018 dollars
      for the screening program and from 420,077 dollars to 468,320 dollars for the
      treatment program. The cost of the screening program ranged from 149 dollars to
      234 dollars per student and the cost of the treatment program ranged from 90
      dollars to 115 dollars per session. These costs were estimated from the
      perspective of society. Applying economic cost analysis methods in a real-world
      school setting is challenging, but the process can generate useful estimates.
      Cost analyses and cost-effectiveness studies are needed in this area.

PMID- 15473103
TI  - Children of mothers diagnosed with serious mental illness: patterns and
      predictors of service use.
AB  - Children who have a parent diagnosed with a mental illness are at risk of
      psychiatric and behavioral problems; yet, these children do not necessarily
      receive needed services. Research has investigated correlates of child mental
      health service use, but not for these high-risk children. This study is part of
      an NIMH-funded, longitudinal investigation and describes child problems, service
      use, and predictors of service use for 506 children of 252 mothers diagnosed with
      serious mental illness. Mothers are primarily poor, minority women from urban
      areas. A multilevel-model approach is used to examine service use for multiple
      siblings in a family. More than one third of children had received services (from
      school or mental health agencies) in their lifetimes. Service use was predicted
      by child demographic characteristics (being male, non-African American, and
      older), social context variables (more negative life events, less financial
      satisfaction, and more parenting dissatisfaction), and maternal psychiatric
      variables (positively by high levels of case management receipt and affective
      diagnoses, negatively by maternal substance abuse history). In a subsample of
      "target children," mothers' rating of child behavior problems additionally
      predicted service use. Implications of results for research and intervention are
      discussed.

PMID- 15473104
TI  - Cognitive functioning predicts outpatient service utilization in schizophrenia.
AB  - Aim of the study was to evaluate the cognitive and symptom predictors of
      outpatient service utilization in schizophrenia. The relationships between
      cognitive functioning (verbal learning and memory, executive functions), symptoms
      (positive symptoms, negative symptoms), and outpatient service utilization (case
      management, medication monitoring), were examined in 20 patients receiving
      outpatient services at a psychosocial clubhouse over a 12-month period. Executive
      functions, as measured on the Wisconsin Card Sorting Test (WCST), were the only
      significant predictor of outpatient service utilization, accounting for over 20%
      of the variance in total outpatient services used, with greater impairment
      associated with higher service utilization. Specifically, poorer performance on
      the WCST was associated with delivery of more case management services, but not
      medication management services. More case management services may be required to
      compensate for impairments in executive functioning in patients with
      schizophrenia.

PMID- 15473105
TI  - Electrical distribution system strategies.

PMID- 15473106
TI  - Dynamic approach vital.

PMID- 15473107
TI  - Large scale Legionella monitoring.

PMID- 15473108
TI  - Prescription for pharmacy efficiency.

PMID- 15473109
TI  - Meeting the design challenge.

PMID- 15473110
TI  - Maintaining power continuously.

PMID- 15473111
TI  - A helping hand for infection control.
AB  - Despite considerable awareness amongst the healthcare community about the
      importance of hand hygiene in controlling Healthcare Acquired Infections (HAIs),
      the problem persists. Mike Allen of Dart Valley Systems explores the issues
      surrounding good hand hygiene practice in UK hospitals.

PMID- 15473112
TI  - A specialist supplier's view.

PMID- 15473113
TI  - Measures used to assess burden among caregivers of stroke patients: a review.
AB  - OBJECTIVE: To describe measures used to evaluate the burden of caregiving
      experienced by caregivers of stroke patients and their clinimetric properties.
      DESIGN: A review of the literature was conducted to examine burden scales with
      regard to concept, feasibility, internal consistency, validity, reliability and
      responsiveness. RESULTS: The literature search resulted in 45 measures of
      caregiver outcomes, including 16 different measures of caregiver burden. About
      half of the scales were used only once and were not further described. Nearly all
      instruments measure the various dimensions of burden (competency, negative
      feelings, social relations, participation problems, physical and mental health
      and economic aspects), but not in the same proportions. Most measures showed good
      internal consistency, and validity was demonstrated for all measures except one.
      However, not much is known about the reliability and responsiveness of these
      measures. CONCLUSIONS: No measure has proven superiority above others. Future
      research should focus on comparisons between existing instruments and on their
      reliability and responsiveness.

PMID- 15473114
TI  - Randomized clinical trial into the impact of rigid foot orthoses on balance
      parameters in excessively pronated feet.
AB  - OBJECTIVE: To evaluate the effect of rigid foot orthoses on balance parameters in
      participants with clinically diagnosed excessively pronated feet. DESIGN:
      Randomized clinical trial. SETTING: University biomechanics laboratory.
      PARTICIPANTS: Thirty female and 20 male healthy participants (mean 23.8+/-2.2
      years old) with excessively pronated feet, according to a validated foot
      classification system were randomly assigned to either a control or intervention
      group. INTERVENTIONS: Balance testing was performed using the Balance Performance
      Monitor with an over-the-counter rigid foot orthoses. MAIN OUTCOME MEASURES:
      Standing balance in the form of mean balance (measures the participants ability
      to stand with an even load), medial-lateral sway and anterior-posterior sway. All
      participants were measured while standing bipedally. RESULTS: There was no
      significant mean difference in balance scores between the control and
      intervention group at baseline. After four weeks the results demonstrated no
      significant differences between mean% balance (p >0.05) and anterior-posterior
      sway (p >0.05). However, there was a reduction with the intervention group in
      medial-lateral sway (p=0.02). CONCLUSION: The use of foot orthoses in the current
      study may have improved postural control by stabilizing the rear foot and thus
      maintaining balance. By the same argument, the benefits of limiting excessive
      foot pronation may contribute to effective control of internal rotation of the
      tibia and thereby reduce counter-rotatory motion at the knee and lower leg and
      maintain balance.

PMID- 15473115
TI  - Fewer accidents and better maintenance with active wheelchair check-ups: a
      randomized controlled clinical trial.
AB  - OBJECTIVE: To investigate whether active intervention using a compiled checklist
      for wheelchair check-ups increases user satisfaction and/or decreases accidents,
      near accidents and pressure sores. DESIGN: A randomized controlled trial
      comparing active intervention versus standard intervention for prescribed,
      manually propelled wheelchairs. SETTING: Patients within primary health care of
      Boras and Bollebygd municipalities, a mixed urban and rural population. SUBJECTS:
      Users of manually propelled wheelchairs over 16 years of age. INTERVENTIONS: The
      accident rate, extent of pressure sores, number and extent of repairs,
      reconditioning, adjustments as well as user satisfaction were measured initially
      and at one year. In the standard intervention, the user and carer were encouraged
      to initiate contact when necessary. In the active intervention, an occupational
      therapist performed a scheduled, thorough check-up of the wheelchair, following a
      compiled checklist for safety, comfort and positioning, manoeuvrability and
      transportation. RESULTS: Of 253 registered wheelchair users, 216 were suitable
      and randomized. In the active intervention group, 99% (95% confidence interval 96
      100%) of the inspected wheelchairs required maintenance. The incidence of
      accidents was unchanged in the standard intervention group, but decreased to 'no
      accidents' in the active intervention group (p = 0.03). User satisfaction was not
      affected by the active intervention. CONCLUSION: Most wheelchair users are unable
      to determine on their own when adjustments are needed. An active check-up on
      manually propelled wheelchairs seems to reduce accidents. More information is
      available at http://www.wheelchair.se

PMID- 15473116
TI  - Aerobic treadmill plus Bobath walking training improves walking in subacute
      stroke: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the immediate and long-term effects of aerobic treadmill
      plus Bobath walking training in subacute stroke survivors compared with Bobath
      walking training alone. DESIGN: Randomized controlled trial. SETTING:
      Rehabilitation unit. SUBJECTS: Fifty patients, first-time supratentorial stroke,
      stroke interval less than six weeks, Barthel Index (0-100) from 50 to 80, able to
      walk a minimum distance of 12 m with either intermittent help or stand-by while
      walking, cardiovascular stable, minimum 50 W in the bicycle ergometry, randomly
      allocated to two groups, A and B. INTERVENTIONS: Group A 30 min of treadmill
      training, harness secured and minimally supported according to patients' needs,
      and 30 min of physiotherapy, every workday for six weeks, speed and inclination
      of the treadmill were adjusted to achieve a heart rate of HR: (Hrmax
      HRrest)*0.6+HRrest; in group B 60 min of daily physiotherapy for six weeks. MAIN
      OUTCOME MEASURES: Primary outcome variables were the absolute improvement of
      walking velocity (m/s) and capacity (m), secondary were gross motor function
      including walking ability (score out of 13) and walking quality (score out of
      41), blindly assessed before and after the intervention, and at follow-up three
      months later. RESULTS: Patients tolerated the aerobic training well with no side
      effects, significantly greater improvement of walking velocity and capacity both
      at study end (p =0.001 versus p =0.002) and at follow-up (p <0.001 versus p
      <0.001) in the experimental group. Between weeks 0 and 6, the experimental group
      improved walking speed and capacity by a mean of.31 m/s and 91 m, the control
      group by a mean of 0.16 m/s and 56 m. Between weeks 0 and 18, the experimental
      group improved walking speed and capacity by a mean of 0.36 m/s and 111 m, the
      control group by a mean of 0.15 m/s and 57 m. Gross motor function and walking
      quality did not differ at any time. CONCLUSIONS: Aerobic treadmill plus Bobath
      walking training in moderately affected stroke patients was better than Bobath
      walking training alone with respect to the improvement of walking velocity and
      capacity. The treatment approach is recommended in patients meeting the inclusion
      criteria. A multicentre trial should follow to strengthen the evidence.

PMID- 15473117
TI  - Assessment of muscle strength and motor fatigue with a knee dynamometer in
      subjects with multiple sclerosis: a new fatigue index.
AB  - OBJECTIVE: To measure muscle strength and motor fatigue with a knee dynamometer
      and to assess the intra-rater reliability of measurements for maximal isometric
      extensor and flexor torques and the reliability of a new fatigue index (FI) in
      patients with mild to moderate multiple sclerosis (MS). DESIGN: Repeated
      assessments with one-week intervals. SETTING: The Masku Neurological
      Rehabilitation Centre, Masku, and the Social Insurance Institution, Research
      Department, Turku, Finland. SUBJECTS: Twenty-eight MS patients. OUTCOME MEASURES:
      Maximal isometric torque during 5 s and fatigue of knee flexors and extensors
      during isometric contractions of 30 s were assessed. A new FI was established and
      compared with the two previously used indices (FI1 and FI2). All three indices
      are based on the calculated area under the force versus time curve (AUFC), with
      FI1 using the 30-s recording time in its entirety and F2 omitting the initial 5 s
      in the calculation. In the new fatigue index (FI3), the time point of maximum
      (TPM) torque achieved by the subject is used as the starting point in the
      calculation. The patient's subjective fatigue was measured by Fatigue Severity
      Scale (FSS). RESULTS: The intraclass correlation coefficient (ICC) was 0.97 in
      maximal isometric torque measurements. FI3 showed good intra-rater reliability
      (ICC =0.68-0.86). None of the fatigue indices correlated with FSS. CONCLUSIONS:
      Maximal isometric torque and motor fatigue of knee flexor and extensor muscles
      can be reliably measured using a knee dynamometer in MS patients. The new FI
      proved to be a reliable model for MS patients.

PMID- 15473118
TI  - Validity of the Canadian Occupational Performance Measure: a client-centred
      outcome measurement.
AB  - OBJECTIVE: To study the convergent and divergent validity of the Canadian
      Occupational Performance Measure (COPM). DESIGN: Cross-sectional study. SETTING:
      The occupational therapy departments of two university hospitals in Amsterdam.
      SUBJECTS: One hundred and five consecutive outpatients. OUTCOME MEASURES: The
      COPM is a measure of a client's self-perception of occupational performance in
      the areas of self-care, productivity and leisure. Outcome measures of the COPM
      are: the client's most important problems in occupational performance and a total
      score for performance and a total score for satisfaction for these problems.
      Problems reported in the COPM were compared with the Sickness Impact Profile
      (SIP68), the Disability and Impact Profile (DIP) and an open-ended question.
      RESULTS: Complete data were obtained for 99 clients. The identification of
      occupational performance problems with the COPM surpassed the items reported in
      the SIP68, the DIP and the open-ended question, which confirms the surplus value
      of the COPM. Divergent validity was further demonstrated by the low correlation
      coefficients between the total SIP68 scores and the COPM. Seventy-four per cent
      of the occupational performance problems reported in the COPM had a corresponding
      item in the DIP and 49% had a corresponding item in the SIP68. Convergent
      validity was supported by the fact that 63% of the corresponding problems in the
      DIP were reported to be a disruption of quality of life and 74% of the
      corresponding problems in the SIP68 were identified as a disability. CONCLUSION:
      The results of this study provide supportive evidence for the convergent and
      divergent validity of the COPM. The data support the assumption that the COPM
      provides information that cannot be obtained with current standardized
      instruments to measure health.

PMID- 15473119
TI  - Communication during goal-setting in physiotherapy treatment sessions.
AB  - OBJECTIVE: To analyse in detail therapists' and patients' communication practices
      during physiotherapy goal-setting in stroke rehabilitation settings. To deduce
      explanations for observed practices. To contribute to understanding of the
      communication challenges entailed in goal-setting. DESIGN: A conversation
      analytic study of video-recorded treatment sessions. SETTING: Physiotherapy
      'gyms' in four UK hospitals. SUBJECTS: The 74 recorded sessions involved 21
      patients (52-86 years, 11 female) and 10 senior physiotherapists. Patients'
      disabilities varied; none were severely aphasic. Nine of the therapists were
      female, postqualification experience ranged from 3 to 23 years. FINDINGS: Eight
      goal-setting episodes were identified. In all but one, therapists supplied the
      target problems or abilities for which goals were subsequently set. The case in
      which the patient was asked to propose problems prior to goal-setting is examined
      in detail. Various interactional difficulties and delays arose both in eliciting
      the patient's views and incorporating them into agreed goals. Strategies by which
      the therapist dealt with difficulties included repeated and constraining
      questions, negotiation, and amending proposed goals. CONCLUSIONS: Findings of
      this small, detailed study might help explain previous observations of infrequent
      goal-setting and failure to maximize patients' involvement therein. Goal-setting,
      particularly where patients' views are elicited and incorporated, involves skill
      and effort, and is influenced by powerful social constraints. Developing detailed
      knowledge of both practices and constraints may contribute to improving
      professional practice, guidance and education. The paper demonstrates the utility
      of detailed analysis of rehabilitation communication using conversation analytic
      methods.

PMID- 15473120
TI  - What really matters: an inquiry into the relative importance of dimensions of
      informal caregiver burden.
AB  - OBJECTIVE: Prevailing measures of subjective caregiver burden either have no
      overall summary score or do not consider the relative importance caregivers
      attach to different dimensions of burden. Our aim was to assess which dimensions
      informal caregivers perceive as being important to their overall burden from care
      giving. DESIGN: Cross-sectional. SUBJECTS: Data were pooled from two Dutch
      samples of primary informal caregivers covering a wide range of chronic care
      giving situations: caregivers for stroke survivors (n = 196) and caregivers for
      individuals with rheumatoid arthritis (RA) (n = 131). MAIN MEASURES: Subjective
      burden of care giving was assessed using the Caregiver Reaction Assessment (CRA)
      and the Self-Rated Burden scale (SRB). RESULTS: In the total sample four of the
      five dimensions of the CRA were found to contribute to the overall subjective
      burden experienced by informal caregivers. In the individual stroke and RA
      samples only two of the five dimensions emerged as relevant. SRB scores were
      significantly higher for caregivers of stroke patients, but no differences were
      found for the five dimensions of the CRA between the two samples. CONCLUSIONS:
      The dimensions of CRA are not equally important to the overall subjective burden
      of informal caregivers. To assess overall subjective burden, a measure based on a
      caregiver's own assessment of burden such as SRB needs to be used in addition to
      prevailing measures.

PMID- 15473121
TI  - Recovery of the upper limb post ischaemic stroke and the predictive value of the
      Orpington Prognostic Score.
AB  - OBJECTIVE: To document upper limb recovery in stroke patients and investigate
      whether the Orpington Prognostic Score (OPS) performed within 48 hours of
      admission to hospital post ischaemic stroke was a predictor of upper limb
      function at six months and two years. DESIGN: Inception cohort design. SETTING:
      Teaching Hospital. SUBJECTS: One hundred and fourteen patients hospitalized with
      acute ischaemic stroke were stratified into three groups based on their OPS
      within 48 hours of admission post stroke and underwent further assessments at two
      weeks, six months and two years after stroke onset. MAIN MEASURES: Rivermead Arm
      Score (RAS), Nine Hole Peg Test (NHPT) and grip strength (GS). RESULTS: Patients
      with a good OPS and intermediate OPS showed significant recovery in all outcome
      measures for up to six months post stroke (p < 0.05), while those with a poor OPS
      at 48 hours showed no significant improvement (p > 0.05). The OPS score at 48
      hours was the most highly correlated variable with upper limb outcome at six
      months (r= -0.728) and at two years (r= -0.712) compared with other variables
      such as age, class of stroke, sensation, grip strength and RAS. CONCLUSION:
      Stroke patients demonstrate differential upper limb recovery patterns which need
      to be taken in consideration when designing studies that investigate efficacy of
      rehabilitation, and the OPS is highly correlated with upper limb recovery at six
      months and two years.

PMID- 15473122
TI  - Using an interview study of transport use by people who have had a stroke to
      inform rehabilitation.
AB  - INTRODUCTION: Many people who have had a stroke want to get out of their house
      more often. This study explored attitudes and barriers to the use of transport
      with the aim of informing rehabilitation. METHOD: Semi-structured interview study
      of 24 community-dwelling people who had had a stroke, purposively sampled to find
      people with a variety of recent experiences of transport. Interviews were taped
      and transcribed. Analysis was by constant-comparative methodology, to develop
      emerging themes and concepts. RESULTS: Interviewees wanted to travel for specific
      purposes but also for its own sake. Many could no longer use their car. This gave
      them less flexibility to travel and reduced their autonomy. Barriers to using
      alternative forms of transport were fear of injury or embarrassment from falling,
      an associated lack of confidence, inadequate information about transport
      services, perceptions about the cost of taxis and pavement vehicles (scooters)
      and environmental factors such as the weather. Those who could drive, or who
      lived with someone who did, gave the most positive descriptions of transport use.
      Those reliant on family or friends felt they could ask only for help getting to
      health-related appointments and those who used specialist transport services
      provided the most negative descriptions of transport. CONCLUSIONS: Many of the
      barriers to transport use after stroke may be amenable to intervention. An
      intervention package capable of re-enabling people to drive or be driven, to use
      a pavement scooter safely, to provide information about the alternatives and to
      encourage best use of public transport is worth developing.

PMID- 15473123
TI  - Sex-related differences of rehabilitation outcomes of spinal cord lesion
      patients.
AB  - OBJECTIVES: To evaluate sex-related differences of spinal cord lesion patients.
      PATIENTS: Two hundred and eighty-one patients were included with evaluation of:
      lesion to admission time, aetiology, lesion level, associated injury, medical
      complications and surgical intervention, length of stay, American Spinal Injury
      Association (ASIA) impairment and motor scores. MAIN OUTCOME MEASURES: ASIA
      impairment grade and ASIA motor scores; Barthel Index, Rivermead Mobility Index
      and Walking Index for Spinal Cord Injury. RESULTS: In the entire group female
      patients had a lower frequency of traumatic lesions, a lower frequency of
      complications at admission and a higher frequency of incomplete lesions (ASIA
      impairment C). In the matching cohorts comparison female patients showed the same
      neurological and functional recovery as male patients. CONCLUSION: Gender does
      not seems to influence spinal cord rehabilitation outcomes despite the fact that
      men and women showed significant epidemiological differences. Further studies are
      needed to evaluate some aspects such as long-term bladder management and
      complications.

PMID- 15473124
TI  - Is serum ferritin high in patients with diabetic retinopathy? A controlled study.
AB  - It is suggested that an excessive absorption and storage of dietary iron might
      contribute in the pathogenesis of type II diabetes mellitus and its
      complications. However, previous studies had methodological problems including
      design, lack of matched controls and unspecified inclusion criteria. The aim of
      the study was to evaluate the relationship between diabetic retinopathy and serum
      ferritin levels in well-defined diabetic patients and controls. The study
      population comprised of 3 groups: patients with type II diabetes mellitus and
      severe diabetic retinopathy, diabetic patients without retinopathy, and non
      diabetic, non-retinopathy patients. The groups were well matched by age, gender
      and hemoglobin levels, whereas diabetes characteristics and treatment differed.
      Serum iron, transferrin and ferritin levels were compared between the patients'
      groups. Twenty-two patients had diabetes and retinopathy, 29 patients had
      diabetes without retinopathy and 40 were non-diabetic, non-retinopathy patients.
      Serum iron or ferritin levels did not differ significantly between the 3 groups.
      Also, there was no correlation between HbA1c level and serum iron or ferritin
      levels between the 2 diabetic patients' groups. Our findings suggest that iron
      does not have a major role in the development of diabetes mellitus or diabetic
      retinopathy.

PMID- 15473125
TI  - Precise quantitation of steroid 5alpha lambda pi eta alpha-reductase type 1 mRNA
      levels by RT-PCR in female rat liver.
AB  - The liver is a multifunctional organ capable of steroid hormone catabolism. The
      steroid metabolizing enzyme activities have been identified in the liver and it
      has been demonstrated that neonatal testicular androgens irreversibly program
      several hepatic enzyme activities in the rat including 5alpha-reductase (5alpha
      R). In this paper we have applied a quantitative RT-PCR method coupled to laser
      induced fluorescence capillary electrophoresis (LIF-CE) to measure the mRNA
      levels of 5alpha-R type 1 isozyme (5alpha-R1) in the liver of female intact and
      ovariectomized rats. Both groups were treated with testosterone (T) to study the
      possible regulation of 5alpha-R1 by androgens in females and to allow comparison
      with our previous findings in the liver of male rats. Our results demonstrate
      that the 5alpha-R1 mRNA isozyme is higher in the liver of female rats than in
      males and that the regulation of 5alpha-R1 mRNA by T is different in the liver of
      female than in male rats. Finally, our results could point to hepatic 5alpha
      Reductase participation in the female not only in the catabolism of steroids with
      delta4,5 double bond, but also in other physiological functions such as the
      production of 3alpha,5alpha-reduced metabolites of progesterone and
      deoxycorticosterone (DOC), potent allosteric modulators of GABA(A) receptors.

PMID- 15473126
TI  - Comparison of efficacy of sibutramine or orlistat versus their combination in
      obese women.
AB  - OBJECTIVE: Sibutramine and orlistat are currently used for weight loss. We aimed
      to investigate the effect of orlistat and sibutramine combination therapy in
      treatment of obese women. SUBJECTS AND DESIGN: Study population consisted of 89
      obese women who had a body mass index > or = 30 kg/m2, were normotensive, and had
      normal glucose tolerance. All patients were placed on a diet which contained fat
      approximately 30% of total calorie intake and the diet was designed to cause an
      energy deficit of approximately 2.51-3.56 megajoule/day. At the first month of
      diet (baseline), all patients were randomly divided into three therapy groups:
      Diet + Orlistat (group 1; n = 30 patients), Diet + Sibutramine (group 2; n = 29
      patients), Diet + Orlistat + Sibutramine (group 3; n = 30 patients). Body weight,
      body fat distribution and serum lipid levels were evaluated baseline and after
      six months in all subjects. RESULTS: Mean weight loss was 5.5 +/- 4.9 kg (p =
      0.024) in group 1, 10.1 +/- 3.6 kg (p < 0.001) in group 2, 10.8 +/- 6.6 kg (p <
      0.001) in group 3 after the six months. Weight loss was significantly greater in
      group 2 (p = 0.003) and group 3 (p = 0.002) when compared with group 1.
      Percentage of mean weight loss was 5.5 +/- 3.1% in group 1, 10.2 +/- 4.8% in
      group 2, 10.6 +/- 5.7% in group 3. Percentage of weight loss was higher in group
      2 (p = 0.01) and group 3 (p = 0.009) when compared with group 1. Weight loss and
      percentage of weight loss were not different between group 2 and group 3.
      CONCLUSION: These three regimens had different results on weight loss in obese
      women. Combination drug therapy and sibutramine therapy were both more effective
      than orlistat therapy alone. However, no significant difference was noted between
      combination drug therapy and sibutramine treatment groups.

PMID- 15473127
TI  - The effects of diet, sulfonylurea, and Repaglinide therapy on clinical and
      metabolic parameters in type 2 diabetic patients during Ramadan.
AB  - BACKGROUND AND AIM: Diabetes and its treatment can cause problems for the Muslim
      population. The aim of this study was to evaluate the effect of different therapy
      models on clinical and metabolic status in type 2 diabetic patients during
      Ramadan. MATERIAL AND METHODS: Fifty-two type 2 diabetic patients were included
      to this study. Twelve of patients were on diabetic diet only before and during
      Ramadan (Group 1). Forty of patients had had sulfonylurea (Glimepiride 23
      patients, gliclazide 17 patients) before Ramadan. Thirteen of these patients were
      on a single dose sulfonylurea (Glimepiride 8 patients, gliclazide 5 patients)
      (Group 2) and 27 were on Repaglinide 2 x 2 mg (Group 3) during Ramadan. Beta
      hydroxybutyric acid, glucose, fructosamine, HbA1c, lipid levels and body weight
      were measured before and after Ramadan. RESULTS: Body weight, fasting plasma
      glucose, fructosamine, HbA1c, total cholesterol were not changed in groups during
      the study. Triglyceride level decreased after Ramadan in groups 2 (p = 0.002) and
      3 (p = 0.024). HDL-cholesterol level increased in group 3 (p = 0.022). Fasting
      capillary beta-hydroxybutyric acid level increased in group 1 (p = 0.034) and
      didn't change in groups 2 and 3 during the Ramadan. Only one hypoglycemic event
      occurred at day 6 of Ramadan in patients in group 2 (the patient was on 3 mg
      glimepiride). CONCLUSION: Our results conclude that Ramadan fasting affects
      metabolic parameters in type 2 diabetes and hypoglycemia should be kept in mind
      especially in patients using sulfonylurea treatment. Ramadan fasting is not
      advised for type 2 diabetics while taking medical therapy. If the patient wants
      Ramadan fasting, these patients using Repaglinide can reduce the frequency of
      hypoglycemia.

PMID- 15473128
TI  - Effect of leptin on LH levels and hypothalamic release of GnRH. Its relationship
      with the hypothalamic neurotransmitter amino acids system in adult male rats.
AB  - The objective of the present paper was to determine the effect of leptin on the
      reproductive axis in adult male rats, as well as the hypothalamic mechanisms
      involved in this effect. For this purpose, we studied the in vivo effect of
      leptin in adult male rats on serum LH levels, and the in vitro effect on
      hypothalamic GnRH and amino acid neurotrasmitter release. For in vivo
      experiments, animals were injected i.p. with leptin at a dose of 30, 100 and 300
      microg/kg. In the in vitro experiments, hypothalamic samples were incubated for
      60 min in Earle's medium with leptin: 10(-9), 10(-10) and 10(-12) M for GnRH
      determination, and 10(-10) M for amino acids evaluation. Finally, we studied the
      effect of the lowest effective leptin dose on plasma LH levels in peripubertal
      male rats to compare the effect between this group and adults. Leptin induces
      significant decreases of serum LH levels with the different studied doses (p <
      0.01 vs. control) in adult male rats, while in peripubertal male rats, it induced
      a significant (p < 0.01 vs. control) increment in serum LH levels. On the other
      hand, in vitro leptin in adult male rats, significantly decreases GnRH release as
      well as the hypothalamic release of glutamate (GLU). In contrast, leptin
      increased the GABA release by this hypothalamus in these animals. These results
      indicate that leptin has an inhibitory effect on the GnRH-LH axis in adult male
      rats and this effect appears to be connected with an inhibition of hypothalamic
      release of GLU (the excitatory amino acid) and a stimulatory effect on GABA
      release (the inhibitory amino acid). On the other hand, in peripubertal male
      rats, leptin showed a stimulatory effect.

PMID- 15473129
TI  - Effect of maternal malnutrition and anemia on the endocrine regulation of fetal
      growth.
AB  - Fetal growth retardation is a result of a complex pathology caused by multiple
      factors of fetal, placental, and maternal origin. Hormones and growth factors
      released as a result of maternal-fetal physiological interactions play an
      importance role in fetal well being and fetal outcome. Intrauterine Growth
      Retardation (IUGR) is associated with significant perinatal and childhood
      morbidity. It is estimated that 13.7 million infants are born annually with IUGR,
      comprising 11% of all births in developing countries. Both maternal malnutrition
      and anemia are associated with various degrees of fetal growth retardation. The
      relationship between decreasing birth weight percentiles and increasing fetal
      morbidity and mortality has been demonstrated by several investigators and
      epidemiological studies suggest that IUGR is a significant risk factor for the
      subsequent development of chronic hypertension, ischemic heart disease, diabetes,
      and obstructive lung disease in adult life (Barker's Hypothesis). Maternal anemia
      and/or malnutrition are recognized to be the most frequent cause of IUGR and SGA
      birth in developing countries like India. In order to investigate adaptive
      mechanisms by the fetus to overcome the growth disadvantage caused due to
      maternal nutritional limitations, we examined the quantitative variations in
      hormonal and growth factor profiles in paired cord blood and maternal samples
      obtained from neonates born to malnourished and/or anemic mothers. The results of
      our study show that: 1) The percentage of small for gestational age (SGA)
      neonates born to malnourished and anemic mothers was significantly higher than
      those born to mothers who were either malnourished or anemic; 2) Significantly
      higher levels of GH, PRL, HPL and IGF-1 were observed in the cord blood of
      neonates born to malnourished and anemic mothers indicative of an adaptive
      response on part of the fetus to over come an in-utero growth disadvantage; 3)
      The anoxemia-related fetal perturbations may have unique features that make them
      distinct from nutrient deficiency-related IUGR. Thus, these novel observations
      are relevant to the context of the ongoing scientific debate on Barker's
      hypothesis.

PMID- 15473130
TI  - The prevalence and target antigens of antithyroid drugs induced antineutrophil
      cytoplasmic antibodies (ANCA) in Chinese patients with hyperthyroidism.
AB  - OBJECTIVE: Antithyroid drugs such as propylthiouracil (PTU) and methimazole (MMI)
      are common medications in Chinese patients with hyperthyroidism and PTU-induced
      antineutrophil cytoplasmic antibody (ANCA) positive vasculitis has been reported.
      The current cross-sectional study aimed to investigate the prevalence and the
      target antigens of ANCA in Chinese patients with hyperthyroidism pre- and post
      antithyroid medication therapy. METHODS: Sera from 216 patients with
      hyperthyroidism in our hospital were collected from January to July in 2002.
      Patients were divided into four groups: untreated (n = 34); treated with PTU (n =
      62); treated with MMI (n = 77); and treated with both PTU and MMI (n = 43).
      Indirect immunofluorescence (IIF) assay was used to detect ANCA and ANA. Antigen
      specific ELISAs were used to detect antigen specificities. The known antigens
      included myeloperoxidase (MPO), proteinase 3 (PR3), human leukocyte elastase
      (HLE), lactoferrin, bactericidal/permeability-increasing protein (BPI), cathepsin
      G and azurocidin. RESULTS: 33/216 sera were IIF positive, 20 of the 33 samples
      were ANCA positive, 11 samples were ANA positive, and two samples were both P
      ANCA and ANA positive. The prevalence of positive ANCA in patients receiving PTU
      (14/62, 22.6%) was significantly higher than that of untreated patients (1/34,
      2.9%) and patients treated with MMI (0/77, 0), P < 0.017. Of the 22 IIF-ANCA
      positive samples, 12 (54.5%) sera recognized lactoferrin, seven (31.8%) sera
      recognized HLE, four sera recognized MPO and azurocidin respectively, three sera
      recognized PR3 and cathepsin G respectively, and one serum recognized BPI. Six of
      the 22 (27.3%) patients with ANCA positive had clinical evidence of vasculitis.
      All patients with MPO-ANCA and two of the three patients with PR3-ANCA had
      clinical vasculitis. CONCLUSION: PTU is associated with the production of ANCA in
      patients with hyperthyroidism. PTU-induced ANCA are due to polyclonal activation
      of B cells. Anti-MPO and anti-PR3 antibodies may associate the occurrence of
      clinical vasculitis.

PMID- 15473131
TI  - Phytoestrogenic isoflavones daidzein and genistein reduce glucose-toxicity
      induced cardiac contractile dysfunction in ventricular myocytes.
AB  - Epidemiological evidence suggests a reduction in the incidence of coronary heart
      disease, cancer and osteoporosis in populations with a high dietary intake of
      plant estrogen or phytoestrogen. The clinical benefit of phytoestrogens in
      cereals, vegetables and medicinal plants is attracting increasing attention for
      the general public. In the present study, we examined the effect of
      phytoestrogenic isoflavones daidzein and genistein on glucose toxicity-induced
      cardiac mechanical malfunction simulating diabetic cardiomyopathy. Adult rat
      ventricular myocytes were isolated and maintained for 24 hours in normal (NG, 5.5
      mM) or high glucose (HG, 25.5 mM) medium in the absence or presence of
      isoflavones daidzein (50 microM) or genistein (20 microM). Cardiac contractile
      indices were evaluated using an IonOptix MyoCam system including peak shortening
      (PS), maximal velocity of shortening/relengthening (+/- dL/dt), time-to-PS (TPS)
      and time-to-90% relengthening (TR90). Myocytes maintained in HG medium displayed
      altered mechanical function simulating in vivo diabetes including reduced PS, +/-
      dL/dt and prolonged TR90 associated with normal TPS compared to those from NG
      myocytes. Interestingly, these HG-induced mechanical dysfunctions were abolished
      by co-incubation of daidzein or genistein. However, daidzein but not genistein
      itself depressed PS in NG myocytes. Neither daidzein nor genistein affected any
      other mechanical parameters tested in NG myocytes. Collectively, these data
      suggest that the phytoestrogenic isoflavones daidzein and genistein may reduce
      glucose toxicity-induced cardiac mechanical dysfunction and thus possess
      therapeutic potential against diabetes-associated cardiac defects.

PMID- 15473132
TI  - Effects of growth hormone on insulin signal transduction in rat adipose tissue
      maintained in vitro.
AB  - Growth hormone treatment (GH) decreases adipose tissue sensitivity to insulin.
      However, the exact molecular mechanism(s) involved remains unclear. In the
      present study, we have evaluated the chronic effects of GH on adipose tissue
      explants cultured in a defined media. The objective was to determine the effects
      of GH treatment for 24 and 48 hours on the early steps of the insulin signal
      transduction, including IRS-3. The 24-hour culture media contained no hormones or
      100 ng/ml GH. The 48-hour culture media contained insulin and dexamethasone
      supplemented with or without 100 ng/ml of GH. Results demonstrated a reduction in
      the cellular concentration of IRS-1 by around 30% when adipose tissue was
      chronically treated with growth hormone for either 24 or 48 hours. IRS-3 protein
      levels were also decreased by 15% after the 24-hour treatment, and by 27% after
      culture with GH for 48 hours in the presence of insulin and dexamethasone. PI 3
      kinase concentrations were also reduced by GH in both experiments by around 25%.
      At the end of the 24-hour culture with GH adipose explants were stimulated with
      insulin in a short-term incubation, after which phosphorylation and association
      of the IRSs with PI 3-kinase were evaluated. After the insulin stimulus, the
      association of PI 3-kinase with IRS-1 and IRS-3 were decreased in explants
      chronically cultured with GH by 44 and 28%, respectively. After this short-term
      insulin stimulus, the IRS-3 phosphorylation was also lowered in GH-treated
      explants. The results with chronic cultures of adipose presented here are
      consistent with similar changes in IRS-1 and IRS-2 concentration and
      phosphorylation observed for liver and muscle after long-term (3-5 days) in vivo
      treatment with GH. The data suggest that chronic GH treatment alters the early
      steps of the insulin signal transduction pathway, and may explain the changes in
      adipose tissue sensitivity to insulin.

PMID- 15473133
TI  - Familial acromegaly: a familial report and review of the literature.
AB  - Familial acromegaly without features of multiple endocrine neoplasie type 1 (MEN
      1) is an exceptional clinical entity. We report in this article three cases of
      acromegaly due to pituitary macroadenomas without any other endocrinopathy in a
      family. A 31-year-old woman (subject A) and her 34-year-old sister (subject B)
      with elevated basal rolactin (PRL) levels, elevated growth hormone (GH) levels
      during the oral glucose tolerance test (OGTT) and a pituitary adenoma in Computed
      Tomography (CT) and Magnetic Resonance Imaging (MRI) were diagnosed as
      acromegaly. Subject A was treated only with radiotherapy and Lysuride. Subject B
      underwent transsphenoidal microsurgical extirpation 15 years ago. 11 years later
      her 24-year-old son (subject C) also presented with typical signs of acromegaly,
      elevated basal PRL level and elevated GH levels during OGTT. A pituitary
      macroadenoma was identified by MRI and he also underwent transsphenoidal
      adenomectomy. Pathology reports confirmed the diagnosis of GH-secreting pituitary
      adenoma in subject B and C. Immunocytochemistry revealed that tumours of subject
      B (> 20% of tumour cells) and C (> 50% of tumour cells) were positive for GH.
      Tumours of subject B (> 10% of tumour cells) and C (> 50% of tumour cells) also
      exhibited immunoreactivity for PRL. On investigation of histocompatibility
      antigens, it was observed that the subject A, B, and C shared the same haplotypes
      [HLA A24(9), HLA B13(6), HLA B35, HLA DQ7(3), HLA DR13(6)] and so it is very
      possible that investigation of HLA antigens in patients with pituitary tumour,
      contributes to better identification of its familial nature and frequency. Here
      we describe an acromegaly family and the distributions of HLA antigens.

PMID- 15473134
TI  - The effects of hypothyroidism in rats on serum leptin concentrations and leptin
      mRNA levels in adipose tissue and relationship with body fat composition.
AB  - Both thyroid hormones and leptin affect sympathetic nervous system activity,
      basal metabolic rate, body fat mass, food intake, and thermogenesis, and each one
      also affects the actions of the other. We examined the alterations in serum
      leptin concentrations and leptin mRNA expression in hypothyroid rats and
      investigated the relation between serum leptin and leptin mRNA levels with the
      total adipose tissue mass and total body weight. Twenty male Wistar rats were
      divided into 2 groups, euthyroid and hypothyroid. Their body compositions were
      examined by Dual Energy X-ray Absorptiometry at the beginning and end of the
      study. Serum leptin concentrations and levels of leptin mRNA in the
      retroperitoneal white adipose tissue were measured at the end of the study. Serum
      leptin concentrations did not show any difference between the two groups (1.9 +/-
      0.2 ng/ml in the hypo and euthyroid group, P > 0.05), but the fat mass of the
      hypothyroid rats were lower than the euthyroid rats (21.1 +/- 2.5 g in the
      euthyroid group and 14.2 +/- 1.9 g in the hypothyroid group, P > 0.05 between
      groups at the end of the study) although the difference between the groups was
      statistically not significant. Leptin mRNA level was significantly higher in the
      hypothyroid group than in the euthyroid group (21.6 +/- 1.6 vs. 15.1 +/- 1.2 ng
      respectively, P = 0.002) although the dissected retroperitoneal fat weight was
      significantly lower in the hypothyroid group versus the euthyroid group (1.0 +/-
      0.2 vs. 1.8 +/- 0.2 g respectively, P = 0.013). In conclusion, the change of
      leptin mRNA expression in white adipocytes was thought to be the direct result of
      hypothyroidism or a compensatory response to metabolic changes caused by
      hypothyroidism.

PMID- 15473135
TI  - Expressional regulation of neuronal and cancer-related genes by estrogen in adult
      female rats.
AB  - Adult female rats were ovariectomized and treated with or without estrogen for
      two weeks. mRNA was obtained from the hypothalamus, uterus, liver, kidney and
      skeletal muscle and analyzed by Northern blotting and/or RT-PCR. We examined two
      types of estrogen-responsive genes from rats, neuronal system-related genes
      (Amphiregulin, AR; Neuropeptide Y-Y1 receptor, NPY-Y1R; Bassoon, BSN; N-Cadherin,
      N-CADH) and estrogen-susceptible cancer-related genes (C-terminal binding protein
      interacting protein, CtIP), based on the results of a cDNA microarray analysis
      which was carried out to profile estrogen-responsive genes in the human breast
      cancer cell line MCF-7. The N-CADH gene showed identical response to that in MCF
      7 cells. In the hypothalamus, all except the AR gene were down-regulated in their
      expression. In other tissues, the expression showed marked differences:
      expression of the BSN gene was not detected by either method, and the NPY-Y1R
      gene showed down-regulation in most tissues except for skeletal muscle. We then
      analyzed the time course of the estrogen-responsiveness of these genes in several
      tissues, finding changes in expression patterns especially in skeletal muscle but
      not in the hypothalamus. Our results show that the estrogen-responsive genes,
      which were demonstrated simply as either up- or down-regulated in their
      expression by estrogen in a human cell line using cDNA microarrays, exhibit
      tissue and temporal-specific expression patterns in adult female rats.

PMID- 15473136
TI  - Assessment of recombinant porcine follicle-stimulating hormone receptor using a
      novel polyclonal ectodomain antibody.
AB  - Follicle-stimulating hormone (FSH) receptors (FSHR) are critically involved in
      mediating the responses of granulosa cells and Sertoli cells to FSH. The dynamic
      changes in cell surface FSH receptors (FSHR) in response to FSH remain unclear in
      part because of the heavy reliance on ligand-binding methodologies. This study
      was designed to determine the molecular and cellular properties of recombinant
      porcine FSHR using a novel, high-affinity purified polyclonal antibody to the
      ectodomain of the pFSHR. A full-length porcine FSHR cDNA was cloned and sequenced
      and recombinant pFSHR protein was stably expressed in a clonal cell line of
      Chinese hamster ovary cells (pFSHR-CHO). Recombinant receptor was stably
      expressed in an ovarian cell line with a density similar to that of porcine
      ovarian cells. A specific polyclonal antibody was generated in chickens to a 100
      amino acid fragment of the pFSHR ectodomain. Immunoblotting, immunoprecipitation,
      indirect immunofluorescence cytochemistry and immunoelectron microscopy were
      performed using affinity-purified antibody to identify recombinant pFSHR in pFSHR
      CHO cells. Immunoblotting of solubilized pFSHR-CHO proteins and
      immunoprecipitation of pFSHR-CHO protein metabolically labeled with 35S
      identified a single 74-kDa band in pFSHR-CHO cells; no bands were visualized in
      mock-transfected CHO cells. Indirect immunofluorescent labeling revealed the
      presence of pFSHR in pFSHR-CHO cells but not in mock-transfected CHO cells.
      Immunoelectron microscopy revealed the highest density of pFSHR associated with
      the plasma membrane and no pFSHR in mock-transfected CHO cells. The chicken anti
      pFSHR antibody is a valuable tool for detecting and monitoring of FSHR using a
      variety of methodologies.

PMID- 15473137
TI  - Protein kinase C (PKC) beta modulates serine phosphorylation of insulin receptor
      substrate-1 (IRS-1)--effect of overexpression of PKCbeta on insulin signal
      transduction.
AB  - In vitro phosphorylation of 180-kDa protein, obtained by immunoprecipitation of
      adipocyte homogenate with anti-IRS-1 antibody was increased with the addition of
      conventional PKC in the presence of Ca2+, phosphatidylserine (PS) and diolein
      (DL). Human purified IRS-1 was phosphorylated by purified conventional PKC (cPKC)
      in the presence of Ca2+/PS/DL. These results suggest that PKC may have a role in
      the serine phosphorylation of IRS-1. In order to clarify the inhibitory effect of
      cPKC on glucose transport mechanism, we examined the overexpression of PKCbeta in
      cultured adipocytes. Overexpression of PKCbeta in adipocytes markedly induced
      mobility shift and serine phosphorylation of IRS-1, whereas overexpression of
      dominant negative PKCbeta (DNPKCbeta) blocked this mobility shift and serine
      phosphorylation of IRS-1. Insulin (10 nM) increased [3H]2-deoxyglucose (2-DOG)
      uptake to 200% from basal level (100%) in cultured adipocytes transfected with a
      vector alone. Overexpression of PKCbeta in adipocytes decreased insulin-induced 2
      DOG uptake to 110%, whereas overexpression of DNPKCbeta increased it to 230%.
      These results suggest that PKCbeta negatively regulates glucose uptake via serine
      phosphorylation of IRS-1 in rat adipocytes.

PMID- 15473138
TI  - Protecting investments in polio eradication: the past, present and future of
      surveillance for acute flaccid paralysis.

PMID- 15473139
TI  - The epidemiology of the outbreak of severe acute respiratory syndrome (SARS) in
      Hong Kong--what we do know and what we don't.
AB  - Severe acute respiratory syndrome (SARS) struck Hong Kong bitterly in the spring
      of 2003, infecting 1755 persons and claiming nearly 300 lives. The epidemic was
      introduced by travellers from southern China, where the disease had originated.
      It started in late February and lasted until early June. Two notable 'super
      spreading' events were reported, one inside a teaching hospital and the other in
      a private housing estate. Other than in the super-spreading events, the
      infectivity in the community appeared to be low, and there were few, if any,
      asymptomatic or subclinical infections. Health-care workers were at particular
      risk and accounted for 22 % of all probable cases. The main modes of transmission
      were through droplet spread and close/direct contacts, but situations conducive
      to aerosol generation appeared to be associated with higher risk. Our review
      suggests that there are still many unknown factors concerning the mode of
      transmission and environmental risk that need to be clarified.

PMID- 15473140
TI  - Assessment of areas at increased risk for poliovirus circulation in Ecuador.
AB  - To assess areas at risk for poliovirus circulation in Ecuador, we first selected
      provinces at highest risk based on low immunization coverage with three doses of
      oral poliovirus vaccine, and a low number of reported cases of acute flaccid
      paralysis (AFP). Subsequently, we reviewed discharge data for the period 1996-
      2000 for diagnoses compatible with AFP in the only two national referral
      hospitals in Quito, and at least two main hospitals in each of the six selected
      provinces. Environmental samples from one or two cities/towns in each selected
      province were tested for poliovirus. Of the 14 identified AFP-compatible cases, 8
      (57%) had been previously reported and investigated. We visited four out of the
      six unreported cases; none of those four had sequelae compatible with
      poliomyelitis. From the 14 environmental samples taken, we identified Sabin
      viruses in six of the samples; no vaccine-derived polioviruses were isolated.
      Using this methodology, we found no evidence of undetected poliovirus circulation
      in Ecuador.

PMID- 15473141
TI  - Factors associated with transmission of severe acute respiratory syndrome among
      health-care workers in Singapore.
AB  - Between 1 and 22 March 2003, a nosocomial outbreak of Severe Acute Respiratory
      Syndrome (SARS) occurred at the Communicable Disease Centre in Tan Tock Seng
      Hospital, Singapore, the national treatment and isolation facility for patients
      with SARS. A case-control study with 36 cases and 50 controls was conducted of
      factors associated with the transmission of SARS within the hospital. In
      univariate analysis, contact with respiratory secretions elevated the odds ratio
      to 6.9 (95 % CI 1.4-34.6, P= 0.02). Protection was conferred by hand washing (OR
      0.06, 95% CI 0.007-0.5, P=0.03) and wearing of N95 masks (OR 0.1, 95% CI 0.03
      0.4, P=0.001). Use of gloves and gowns had no effect. Multivariate analysis
      confirmed the strong role of contact with respiratory secretions (adjusted OR
      21.8, 95 % CI 1.7 274.8, P=0.017). Both hand washing (adjusted OR 0.07, 95 % CI
      0.008-0.66, P=0.02) and wearing of N95 masks (adjusted OR 0.1, 95% CI 0.02-0.86,
      P=0.04) remained strongly protective but gowns and gloves had no effect.

PMID- 15473142
TI  - A syphilis outbreak in remote Australia: epidemiology and strategies for control.
AB  - This paper describes the epidemiology of a syphilis outbreak in remote Australia,
      and explores contributing factors and control strategies. Between 1 August 2000
      and 31 January 2002, 74 cases of early syphilis (42 female, 32 male) were
      identified in 73 Kimberley residents. Syphilis rates in age groups 10-19 and 20
      29 years were 583 and 439 per 100000 person years respectively. Factors
      contributing to the outbreak included incompleteness of sexually transmitted
      infection (STI) clinical management, untimely contact tracing, staffing and
      management issues, and poor community knowledge about STIs. Outbreak control
      strategies addressed factors that could be influenced by changes in health
      service delivery, and focused on providing education and support to health staff,
      and efforts to increase community knowledge about sexual health. Although some
      improvements have occurred, the outbreak is still continuing. Until open and
      honest discussion and a collaborative approach is taken toward STI problems
      affecting Indigenous Australians, outbreaks such as this will continue to occur.

PMID- 15473143
TI  - Preliminary report on the northern Australian melioidosis environmental
      surveillance project.
AB  - An environmental surveillance programme was developed to determine whether water
      supplies could be a source of Burkholderia pseudomallei as noted during previous
      melioidosis outbreak investigations. Water supplies to communities in the three
      northern Australian jurisdictions (Western Australia, Northern Territory and
      Queensland) were sampled periodically during 2001 and 2002. Water and soil
      samples were collected from communities known to have had recent culture-positive
      melioidosis cases and nearby communities where no cases had been diagnosed.
      Clinical isolates of B. pseudomallei obtained from northern Australian patients
      during 2001 and 2002 were compared with the environmental B. pseudomallei
      isolates by ribotyping and pulsed-field gel electrophoresis. B. pseudomallei was
      isolated from 11 distinct locations, all in the Northern Territory, seven of
      which were associated with culture-positive melioidosis cases (>1 case at three
      locations). Water was implicated as a possible environmental source of
      melioidosis in six locations. A variety of free-living amoebae including
      Acanthamoeba and Hartmannella spp. that are potential hosts to B. pseudomallei
      were recovered from environmental specimens. Culturable B. pseudomallei was not
      found to be widely dispersed in the environments sampled.

PMID- 15473144
TI  - Factors influencing length of hospital stay in community-acquired pneumonia: a
      study in 27 community hospitals.
AB  - We did a retrospective study of 1920 episodes of community-acquired pneumonia
      (CAP) in 27 community hospitals and analysed inter-hospital variability in length
      of hospital stay (LOS), mortality and readmission rates. The overall adjusted LOS
      (mean+/-S.D.) was 10.0+/-9.8 days. LOS increased according to the Pneumonia
      Severity Index (PSI) risk class: 7.3 days for class I to 11.3 days for class V
      (P<0.001). In a multiple regression model, LOS increased (P<0.001) according to
      the hospital (inter-hospital variability), PSI risk class, complications during
      hospitalization, admission to ICU, need of oxygen and transfer to a nursing home.
      Hospitals with shorter LOS did not show an increased readmission rate (adjusted
      OR 1.02, 95% CI 0.51-2.03, P = 0.97) and post-discharge mortality (adjusted OR
      1.20, 95% CI 0.70-2.05, P=0.51). There are significant inter-hospital variations
      in LOS in patients with CAP which are related to differences in clinical
      management. The reduction of these differences will further improve efficiency
      and quality of care.

PMID- 15473145
TI  - Carriage of capsulated strains of Staphylococcus aureus: a population-based study
      performed in Gulbarga, South India.
AB  - Staphylococcus aureus is a common human pathogen in community- and hospital
      acquired infections and its capsule is involved in pathogenesis. We report here
      the identification of type-5 and type-8 capsular antigens of S. aureus and the
      prevalence of such strains among volunteers in various age and population groups
      from different locations in India. S. aureus carriage rates varied between 18 and
      50% with the highest values among university students and the lowest in
      schoolchildren, aged 6-20 years. There was no difference in carriage rates for
      males vs. females (P=0.415) or in the socioeconomic status of carriers vs. non
      carriers or age dependence. Among the carriage isolates 21% were type-5, 52% were
      type-8 and the remaining 27% were non-typable. Among invasive isolates these
      percentages were 6, 64 and 30 respectively. This implies that type-5 strains may
      be less invasive than type-8 strains (P=0.0015).

PMID- 15473146
TI  - Population-based Toxoplasma seroprevalence study in The Netherlands.
AB  - During 1995--1996 a population-based seroprevalence study was conducted in The
      Netherlands. Risk factors were established for postnatally acquired
      toxoplasmosis. The results were compared with a study conducted during 1987-1988
      in pregnant women in the Southwest of The Netherlands in order to estimate the
      change in seroprevalence. In total, 7521 sera were tested and the national
      seroprevalence was 40.5 % (95 % CI 37.5-43.4). Living in the Northwest, having
      professional contact with animals, living in a moderately urbanized area, being
      divorced or widowed, being born outside The Netherlands, frequent gardening and
      owning a cat were independently associated with Toxoplasma seropositivity. Risk
      factors like eating undercooked meat could not be studied. The seroprevalence
      among women aged 15-49 years was 10 % lower (35.2 %, 95 % CI 32.9-38.6) in the
      study of 1995-1996, compared to the Toxoplasma study of 1987--1988 (45.8 %, 95 %
      CI 45.2-46.3). The steepest rise in seroprevalence still occurred among the
      subjects aged 25-44 years.

PMID- 15473147
TI  - Seroprevalence and some correlates of Helicobacter pylori at adult ages in
      Gulveren Health District, Ankara, Turkey.
AB  - The purpose of the study was to detect the frequency and distribution of
      Helicobacter pylori in the Gulveren Health Centre service area among residents
      aged between 25 and 64 years and to evaluate the relation of H. pylori infections
      with general health status, socioeconomic status, and some lifestyle habits. The
      study included a representative sample of Gulveren Health Centre residents, aged
      between 25 and 64 years. A stratified random sample of 1672 individuals was
      selected for study purposes out of 10,569 residents, stratified by age and
      gender. A standardized questionnaire was completed for all study participants
      using a face-to-face interview and all participants were invited to the local
      health centre for a thorough physical examination and blood tests. The overall
      prevalence of H. pylori was found to be 77.5 % among individuals aged between 25
      and 64 years. The frequency of H. pylori was higher among individuals with low
      socioeconomic status; those who migrated to Ankara after the age of 20 years;
      members of large families (household size of 4 or above); non-alcohol drinkers;
      and those who regularly drink tea.

PMID- 15473148
TI  - Seroprevalence of IgG against conformational and linear capsid antigens of
      parvovirus B19 in Italian blood donors.
AB  - Serum samples from 446 Italian blood donors between 18 and 65 years of age were
      analysed for the presence of IgG against parvovirus B19 capsid proteins VP1 and
      VP2 including conformational and linear epitopes. The overall prevalence of IgG
      against parvovirus B19 capsid proteins VP1 and VP2 against at least one antigen
      type was 79.1 %. No significant difference was found between men and women. In
      the 18-27 years age group, 77.0 % of the population had experienced infection
      with the virus, reaching 88.5 % in the 48-57 years age group. The overall
      prevalence of IgG was 78.0 % against conformational VP1 + VP2 antigens, 74.9 %
      against conformational VP2, 70.9 % against linear VP1 and 23.3 % against linear
      VP2 in the analysis of the IgG response against different conformational and
      linear epitopes of VP1 and VP2. Although IgG against conformational VP1+VP2,
      conformational VP2 and linear VP1 was present in more than 60 % of subjects in
      all age groups, IgG against VP2 linear antigens was present in only 32% of
      subjects in the 18-27 years age group and then decreased to 20.5 % in the 28-37
      years age group. A different trend was noted when IgG positivity against linear
      and conformational epitopes was analysed separately in men and women. A
      significant increase was found in seroprevalence of IgG against VP2
      conformational antigens with increasing age in males and a significant decrease
      in seroprevalence of IgG against VP2 linear antigens in women with increasing
      age.

PMID- 15473149
TI  - Risk factors for transmission of foodborne illness in restaurants and street
      vendors in Jakarta, Indonesia.
AB  - In a previous risk factor study in Jakarta we identified purchasing street food
      as an independent risk factor for paratyphoid. Eating from restaurants, however,
      was not associated with disease. To explain these findings we compared 128 street
      food-vendors with 74 food handlers from restaurants in a cross-sectional study in
      the same study area. Poor hand-washing hygiene and direct hand contact with
      foods, male sex and low educational level were independent characteristics of
      street vendors in a logistic regression analysis. Faecal contamination of
      drinking water (in 65 % of samples), dishwater (in 91 %) and ice cubes (in 100 %)
      was frequent. Directly transmittable pathogens including S. typhi (n = 1) and non
      typhoidal Salmonella spp. (n = 6) were isolated in faecal samples in 13 (7 %)
      vendors; the groups did not differ, however, in contamination rates of drinking
      water and Salmonella isolation rates in stools. Poor hygiene of street vendors
      compared to restaurant vendors, in combination with faecal carriage of enteric
      pathogens including S. typhi, may help explain the association found between
      purchasing street food and foodborne illness, in particular Salmonella
      infections. Public health interventions to reduce transmission of foodborne
      illness should focus on general hygienic measures in street food trade, i.e. hand
      washing with soap, adequate food-handling hygiene, and frequent renewal of
      dishwater.

PMID- 15473150
TI  - Salmonella Enteritidis outbreak associated with a school-lunch dessert: cross
      contamination and a long incubation period, Japan, 2001.
AB  - A Salmonella Enteritidis (SE) outbreak in Japan was investigated with an
      observational study, analytical epidemiology and bacteriological examination
      (including phage typing). The outbreak occurred among 96 schoolchildren, and was
      caused by SE phage type 1. The outbreak source was dessert buns served at a
      school lunch (RR 42.55, 95 % CI 5.93-305.11, P < 0.001). The buns were probably
      cross-contaminated from eggs from a factory with a history of SE-contaminated
      products. The incubation period was longer than usual (3-16 days, median 8 days).
      A low contaminating dose may account for the long incubation period and low
      attack rate. Outbreak detection was hampered by the absence of routine Salmonella
      surveillance in Japan. The investigation was complicated by concurrent illnesses
      from other SE phage types. It was successful, in part, because adequate food
      samples were available for microbiological testing.

PMID- 15473151
TI  - Outbreak of Salmonella Goldcoast infections linked to consumption of fermented
      sausage, Germany 2001.
AB  - Salmonella Goldcoast (SGC), an uncommon serotype in Germany, was identified in 25
      isolates between 1 April and 7 May 2001. To determine the cause of the outbreak,
      we conducted a matched case-control study including 24 cases and 51 controls. In
      a multivariable regression model, only consumption of a raw fermented sausage
      manufactured by a local company remained significant (adjusted odds ratio 20.0,
      95 % confidence interval 2.7-302.5). SGC isolated from case-patients shared an
      indistinguishable pulsed-field gel electrophoresis pattern. A part of the
      produced raw fermented sausage was sold after only 4 days of fermentation.
      Samples from the premises and products of the company were negative for SGC.
      However, short-time raw fermented sausage is more likely to contain pathogens.
      Irradiation of raw ingredients is not accepted by German consumers, thus strict
      adherence to good manufacturing practices, the use of HACCP programmes as well as
      on-farm programmes remain crucial to reduce Salmonella.

PMID- 15473153
TI  - Salmonella bacteriuria: an increasing entity in elderly women in the United
      States.
AB  - Salmonellosis is a major cause of gastroenteritis in the United States and can
      lead to septicaemia, and other extra-intestinal illness including urinary tract
      infections (UTIs). To examine trends in Salmonella bacteriuria in the United
      States, surveillance data from the National Salmonella Surveillance System from
      1980 to the end of 1999 were reviewed. Overall, 17442 urinary Salmonella isolates
      were reported, representing 2% of all Salmonella isolates from a known source.
      This proportion increased from 2% during 1980--1984 to 4% during 1995--1999. The
      median age of persons from whom these isolates came was 51 years; 12,176 (70 %)
      were women. Compared to the last national survey conducted between 1968 and 1979,
      the rate of Salmonella bacteriuria increased among women, from 2.0 per million
      persons in 1980 to 3.7 in 1999; the highest rate occurring in women > or = 70
      years. National reporting of Salmonella bacteriuria increased in absolute
      incidence and as a proportion of all Salmonella, especially in elderly women and
      may represent an increase in the incidence of Salmonella UTIs. Better
      understanding of the uropathogenicity of Salmonella serotypes may further clarify
      the mechanisms of Salmonella UTIs.

PMID- 15473152
TI  - Outbreak of Salmonella Livingstone infection in Norway and Sweden due to
      contaminated processed fish products.
AB  - In Europe, the number of reported sporadic human cases of Salmonella Livingstone
      infection is low, and outbreaks are rare. We report the largest S. Livingstone
      outbreak described in the literature having an identified source of infection. In
      February 2001, an increased incidence of infection caused by S. Livingstone was
      observed in Norway and Sweden. By July 2001, 44 cases were notified in Norway and
      16 in Sweden. The median age was 63 years, and 40 were women. There were three
      deaths, and 22 patients were hospitalized. Based on standardized questionnaires
      and retrospective studies of S. Livingstone strains in Norway and Sweden, food
      items with egg powder were suspected, and S. Livingstone was subsequently
      recovered from a processed fish product at the retail level. Analysis by pulsed
      field gel electrophoresis documented that isolates from the fish product belonged
      to the same clone as the outbreak strain.

PMID- 15473154
TI  - A European longitudinal study in Salmonella seronegative- and seropositive
      classified finishing pig herds.
AB  - Surveillance and control are important aspects of food safety assurance
      strategies at the pre-harvest level of pork production. Prior to implementation
      of a Salmonella surveillance and control programme, it is important to have
      knowledge on the dynamics and epidemiology of Salmonella infections in pig herds.
      For this purpose, 17 finishing pig herds initially classified as seropositive and
      15 as seronegative, were followed for a 2-year period through serological and
      bacteriological sampling. The study included 10 herds from Denmark, 13 from The
      Netherlands, 4 from Germany and 5 from Sweden and was performed between October
      1996 and May 1999. The Salmonella status of finishing pig herds was determined by
      an initial blood sampling of approximately 50 finishing pigs close to market
      weight per herd. The development of the Salmonella status of the selected herds
      was assessed at seven subsequent sampling rounds of 25 blood samples from
      finishing pigs, 25 blood samples from grower pigs and 10 pen faecal samples each,
      approximately 3 months apart. The odds for testing finishers seropositive, given
      that growers were found seropositive previously were 10 times higher than if
      growers were seronegative (OR 10.0, 95% CI 3.2-32.8). When Salmonella was
      isolated from pen faecal samples, the herd was more likely to be classified
      seropositive in the same sampling round, compared to no Salmonella being detected
      (OR 4.0, 95% CI 1.1-14.6). The stability of an initially allocated Salmonella
      status was found to vary noticeably with time, apparently irrespective of a
      seropositive or seronegative classification at onset of the study. Given the
      measured dynamics in the occurrence of Salmonella in pig herds, regular testing
      is necessary to enable producers, advisors and authorities to react to sudden
      increases in the Salmonella prevalence in single herds or at a national level.

PMID- 15473157
TI  - A stochastic model of vaccine trials for endemic infections using group
      randomization.
AB  - To clarify the determinants of vaccine trial power for non-typable Haemophilus
      influenzae, we constructed stochastic SIS models of infection transmission in
      small units (e.g. day-care centres) to calculate the equilibrium distribution of
      the number infected. We investigated how unit size, contact rate (modelled as a
      function of the unit size), external force of infection and infection duration
      affected the statistical power for detection of vaccine effects on susceptibility
      or infectiousness. Given a frequency-dependent contact rate, the prevalence,
      proportion of infections generated internally and the power to detect vaccine
      effects each increased slightly with unit size. Under a density-dependent model,
      unit size had much stronger effects. To maximize information allowing inference
      from vaccine trials, contact functions should be empirically evaluated by
      studying units of differing size and molecular methods should be used to help
      distinguish internal vs. external transmission.

PMID- 15473156
TI  - Molecular epidemiology of catheter-related bloodstream infections caused by
      coagulase-negative staphylococci in haematological patients with neutropenia.
AB  - Catheter-related bloodstream infection (CRBSI) caused by coagulase-negative
      staphylococci (CNS) is common in haematological patients with febrile
      neutropenia. As the clinical signs of CRBSI are usually scarce and it is
      difficult to differentiate from blood culture contamination, we tried to confirm
      CRBSI by molecular typing of CNS isolated from paired blood cultures (one from a
      peripheral vein and another from the central venous catheter hub). Blood cultures
      were positive in 59 (36%) out of 163 patients. CNS were isolated in 24 (40%)
      patients; in 14 from paired blood cultures (28 isolates) and in 10 from a single
      blood culture. CNS from paired blood cultures were identified as Staphylococcus
      epidermidis. Antimicrobial susceptibility was determined and bacteria were typed
      by pulsed-field gel electrophoresis (PFGE) of bacterial genomic DNA. In 13
      patients, the antibiotic susceptibility of isolates was identical. The PFGE
      patterns from paired blood cultures were identical or closely related in 10
      patients, thus confirming the presence of CRBSI. In the remaining four patients
      they were unrelated, and suggested a mixed infection or contamination. Since CNS
      isolates from three patients had identical PFGE patterns, they were probably
      nosocomially spread amongst them.

PMID- 15473155
TI  - Asymptomatic carriage of verocytotoxin-producing Escherichia coli O157 in farm
      workers in Northern Italy.
AB  - Faecal samples from 350 farm workers on 276 dairy farms and 50 abattoir employees
      from seven different operations were examined for the presence of Verocytotoxin
      producing Escherichia coli 0157 (VTEC O157) by an O157-specific enzyme-linked
      fluorescent assay followed by immunoconcentration. VTEC O157 was isolated from
      four (1.1%) of the farm workers. A second stool sample was obtained from the
      positive farm workers as well as from their household contacts. VTEC O157 was
      isolated from the wife of one of them. The strains from the same household shared
      the same Verocytotoxin genes profile, phage type and pulsed-field gel
      electrophoresis pattern. The VTEC O157-positive subjects had neither intestinal
      symptoms at the moment of sampling nor a history of bloody diarrhoea or renal
      failure. Our study seems to confirm the hypothesis that farm residents often
      develop immunity to VTEC O157 infection, possibly due to recurrent exposure to
      less virulent strains of VTEC.

PMID- 15473158
TI  - Risk of fatal adverse events associated with 17DD yellow fever vaccine.
AB  - Yellow fever (YF), an acute infectious disease, is endemic in the north and
      central-west of Brazil. This disease can be prevented by the use of a vaccine. In
      Brazil, four fatal adverse events have been associated with the YF vaccine used
      in the country (17DD vaccine). We briefly describe the last two fatalities, and
      estimate the risk of 17DD-associated fatal adverse events under different
      epidemiological scenarios. Controversies regarding the appropriate denominator
      that enters the estimation of risk serve as a motivation for each proposed
      scenario. The statistical procedures used show optimum behaviour when assessing
      the risk of rare events. Risk estimates vary from 0.043 (95 % CI 0.017-0.110) to
      2.131 (95 % CI 0.109-12.071) fatalities per million doses administered. The
      robust estimates of the risk of fatal adverse events we present constitute an
      important element in future risk-benefit analysis and point to the need for good
      quality vaccine coverage and adverse-events surveillance data to assess the risk
      of vaccination. Although vaccination of YF endemic regions is necessary to
      maintain low disease prevalence, preventive administration of YF vaccine to the
      entire population should be cautiously analysed.

PMID- 15473159
TI  - Modelling transmission, immunity and disease of Haemophilus influenzae type b in
      a structured population.
AB  - An individual-based stochastic simulation model was constructed to study the
      epidemiology of Haemophilus influenzae type b (Hib) transmission, immunity and
      invasive disease. Embedded in a demographic model, the transmission model of Hib
      carriage employs the most important social mixing patterns with three types of
      contact sites (family, day-care group, and school class). The model includes
      immunity against invasive Hib disease, initiated and boosted by Hib carriage and
      cross-reactive bacterial encounters. The model reproduces the observed age
      patterns in Hib carriage and disease in Finland before large-scale use of the Hib
      conjugate vaccines. The model was used to investigate characteristics of Hib
      transmission. The analysis emphasizes transmission between children and adults in
      families while pointing out the importance of pre-school and school-aged children
      in maintaining Hib circulation. Carriage in these age groups is thus identified
      as being essential to target for sustained effects of interventions by
      vaccination.

PMID- 15473161
TI  - Determinants of the geographical distribution of endemic giardiasis in Ontario,
      Canada: a spatial modelling approach.
AB  - Giardiasis surveillance data as well as drinking water, socioeconomic and land
      use data were used in spatial regression models to investigate determinants of
      the geographic distribution of endemic giardiasis in southern Ontario. Higher
      giardiasis rates were observed in areas using surface water [rate ratio (RR)
      2.36, 95 % CI 1.38-4.05] and in rural areas (RR 1.79, 95 % CI 1.32-2.37). Lower
      rates were observed in areas using filtered water (RR 0.55, 95 % CI 0.42-0.94)
      and in those with high median income (RR 0.62, 95 % CI 0.42-0.92). Chlorination
      of drinking water, cattle density and intensity of manure application on farmland
      were not significant determinants. The study shows that waterborne transmission
      plays an important role in giardiasis distribution in southern Ontario and that
      well-collected routine surveillance data could be useful for investigation of
      disease determinants and identification of high-risk communities. This
      information is useful in guiding decisions on control strategies.

PMID- 15473160
TI  - Indirect protection obtained by Haemophilus influenzae type b vaccination:
      analysis in a structured population model.
AB  - We used a structured population model to study factors determining the magnitude
      of indirect protection in Haemophilus influenzae type b (Hib) vaccination. On a
      simulation platform mimicking the population of Finland, a Hib transmission and
      immunity model, including cross-reactive bacterial encounters, was formulated.
      Utilizing different vaccination coverages and vaccine types we could study how
      fast the incidence of Hib disease declined due to direct and indirect vaccination
      effects. With the Finnish vaccination schedule we could reproduce the observed
      disappearance of Hib cases. Our results show that an indirect effect was already
      significant with a relatively low vaccine coverage, even with a vaccine only
      partly reducing carriage acquisition. This suggests that the vaccination schedule
      and vaccine to be used should be chosen to result, in addition to immunological
      memory, in high antibody concentrations, sufficient to reduce carriage, the
      latter being the main factor behind successful elimination of transmission and
      disease.

PMID- 15473162
TI  - Association between Chlamydia trachomatis antibodies and subfertility in the
      Northern Finland Birth Cohort 1966 (NFBC 1966), at the age of 31 years.
AB  - The objective of this study was to assess the serological association between
      previous Chlamydia trachomatis infection and subfertility in a general population
      sample. A nested case (n = 493)-control (n = 986) study in a population-based
      birth cohort consisting of 12,058 live births from the year 1966 was conducted.
      The analysis was restricted to those 6007 cohort members who replied to a postal
      inquiry and participated in a health examination including blood samples at the
      age of 31 years. The presence of C. trachomatis-specific serum IgG antibodies was
      screened by a synthetic peptide-based enzyme-linked immunosorbent assay. All the
      positive sera were further tested by the microimmunofluorescence method using
      immunotype pools and individual immunotypes of C. trachomatis as antigens. An
      association was found between the detection of immunotype-specific C. trachomatis
      antibodies and subfertility both in men and women. The results of the present
      study confirm the serological association between past C. trachomatis infections
      and subfertility in male or female partners of the couple in the population-based
      sample.

PMID- 15473163
TI  - Genetic diversity and antibiotic resistance of clinical and environmental Vibrio
      Cholerae suggests that many serogroups are reservoirs of resistance.
AB  - Vibrio cholerae is an important human pathogen and the cause of cholera. Since
      genetic variation and antibiotic resistance of strains have implications for
      effective treatment of the disease, we examined the genetic diversity and
      antibiotic resistance profile in 92 clinical strains (serogroup O1) and 56
      environmental strains (O1 antigen, 42 strains; non-O1 antigen, 14 strains)
      isolated in Brazil between 1991 and 1999. Clinical and environmental O1 strains
      showed greater drug resistance compared to environmental non-O1 strains. Nearly
      all clinical O1 strains were resistant to one or more antibiotics while half of
      the environmental O1 and non-O1 strains were resistant to one or more
      antibiotics. No plasmids or class 1 integrons were detected in the strains by PCR
      analysis. Multilocus enzyme electrophoresis analysis (MLEE) suggests most of the
      O1 strains belong to a single (South American) clone that is related but
      different to seventh-pandemic strains isolated from other parts of the world. Our
      results show that there is a close genetic relationship between clinical and
      environmental O1 strains and that many serogroups and the environment can be a
      reservoir for antibiotic resistance.

PMID- 15473164
TI  - Vibrio vulnificus septicaemia in Japan: an estimated number of infections and
      physicians' knowledge of the syndrome.
AB  - Questionnaire surveys were implemented to study the incidence and physicians'
      knowledge of Vibrio vulnificus infections in Japan. Registered emergency
      physicians were selected by stratified random sampling for a questionnaire
      survey. A total of 235 out of 386 physicians (61%) responded to the questionnaire
      and 12 V. vulnificus septicaemia cases were reported from 10 respondents. The
      annual estimated number of V. vulnificus septicaemia was calculated as 425 (95 %
      CI 238-752). The study also revealed that only 15.7 % (95 % CI 11.3-21.0) of
      responding physicians had a basic knowledge of V. vulnificus infection. Education
      for both physicians and people in the high-risk group for developing the
      infection (e.g. immunocompromised, chronic liver disease) will be necessary for
      the prevention, early diagnosis and appropriate treatment of the disease.

PMID- 15473165
TI  - Lewis and Secretor status and Helicobacter pylori eradication.

PMID- 15473167
TI  - Hands up for handwriting.

PMID- 15473166
TI  - A note on vaccination against meningococcal meningitis in infants.

PMID- 15473168
TI  - One hundred males with Asperger syndrome: a clinical study of background and
      associated factors.
AB  - The objective of this study was to investigate the background and associated
      factors in a representative group of young males with Asperger syndrome (AS)
      presenting at a specialized autism clinic. One hundred males aged 5 years 6
      months to 24 years 6 months, with a mean age of 11 years 4 months (SD 3y 10mo),
      who had a clinical diagnosis of AS were included in the study. An in-depth review
      of their medical records and neuropsychological test data was performed. There
      was a high rate (51%) of non-verbal learning disability (defined as Verbal IQ
      more than 15 points higher than Performance IQ), but otherwise there was little
      or no support for the notion of right-hemisphere brain dysfunction being at the
      core of the syndrome. There was a very high rate of close relatives with autism
      spectrum problems, but also high rates of prenatal and perinatal problems,
      including prematurity and postmaturity. In comparison with general population
      data, those with AS very often had a combination of genetic and prenatal and
      perinatal risk factors. Non-verbal learning disability test results applied in
      about half the group. There was a subgroup of individuals with AS who had
      macrocephalus. However, there was no support for an association of AS with low
      body mass index.

PMID- 15473169
TI  - Association between visual perceptual deficits and motor deficits in children
      with developmental coordination disorder.
AB  - This study explored the relation between a motor-free visual perceptual deficit,
      different visual-motor integration deficits, and different motor skills in
      children with developmental coordination disorder (DCD). Thirty-six children (22
      males), aged 9 or 10 years, with DCD and a control group (n=36), matched for age
      and sex, were assessed with the Movement Assessment Battery for Children (MABC),
      a ball-catching test, a jumping test, a timed response task to a visual moving
      stimulus, and the Beery-Buktenica Developmental Test of Visual-Motor Integration,
      incorporating copying, visual discrimination, and tracing tasks. Children with
      DCD performed significantly worse than the control group on all measures. The
      visual discrimination task did not correlate significantly with any of the motor
      tasks. The visual timing task correlated significantly with the ball-catching
      test in the DCD group. The copying test was significantly correlated with the
      MABC in the DCD group. The association between visual-perceptual deficits and
      motor tasks was shown to be task specific.

PMID- 15473170
TI  - Changes to medial gastrocnemius architecture after surgical intervention in
      spastic diplegia.
AB  - We assessed the architecture of the medial gastrocnemius in nine children (five
      males, four females; age range 6 to 15 years; mean 10 years 10 months, SD 3 years
      6 months) with spastic diplegia by ultrasound imaging before and after a
      gastrocnemius recession. The children were ambulant (seven independent, one with
      a posterior walker, one using crutches) before and after surgical intervention.
      We compared values for fascicle lengths and deep fascicular-aponeurosis angles
      with those from a group of normally developing children (five males, five
      females; age range 6 to 11 years; mean 8 years 4 months, SD 1 year 4 months).
      Despite a variable interval between assessments (from 56 to 610 days), fascicles
      were shorter (p=0.00226) and the deep fascicular-aponeurosis angle increased
      (p=0.0152) after intervention. Fascicle lengths of patients were similar to those
      in the group of normally developing children before surgery. After surgery,
      fascicles in the group of children with spastic diplegia were shorter than in
      their normally developing peers (p=0.00109). The gastrocnemius recession
      procedure alters muscle architecture, though the degree of fascicular shortening
      varied, with four of the participants in our study losing less than 10% of their
      original fascicular length at maximum dorsiflexion. Increases in ankle-joint
      power in walking, observed after surgical intervention in children with spastic
      diplegia, may be due to a more normal ankle position rather than to improvements
      in the active mechanical performance of the gastrocnemius.

PMID- 15473171
TI  - Influence of gait pattern on the body's centre of mass displacement in children
      with cerebral palsy.
AB  - We assessed the influence of digitigrade gait pattern, topographical types,
      severity of motor involvement, and locomotor experience on the body's centre of
      mass (COM) displacement during gait in children with spastic cerebral palsy (CP).
      Three-dimensional COM displacements were computed from ground reaction forces in
      51 independent digitigrade walkers (29 males, 22 females; mean age 10 years 6
      months, SD 2 years 7 months, range 7 to 15 years). Results obtained from 10
      participants without disabilities (five males, five females), in the same age
      range as the patients with CP, were used as a reference plantigrade group.
      Vertical and forward COM displacements were significantly different between the
      digitigrade and the plantigrade walkers. Neither the topographical type
      (quadriplegia, n=5; diplegia, n=20; right hemiplegia, n=13; left hemiplegia,
      n=13), nor the severity of motor involvement, nor the locomotor experience
      influenced COM displacements. We conclude that the COM displacement during gait
      in patients with CP was mainly influenced by the digitigrade gait pattern
      encountered in this neurological disorder rather than the different topographical
      types and motor involvements.

PMID- 15473172
TI  - Muscle responses to seated perturbations for typically developing infants and
      those at risk for motor delays.
AB  - This study examined spatial and temporal organization of muscle activity in
      response to seated forward platform perturbations in typically developing (TD)
      infants and in infants at risk for ongoing neuromotor delays. Twelve high-risk
      (HR) infants (six males, six females) and 12 TD infants (nine males, three
      females) aged 8 to 10 months (corrected for prematurity), who were all
      independent sitters, participated in this study. Surface electromyograms recorded
      muscle responses to forward perturbation in the neck, trunk, and leg (6cm
      amplitude, 12cm/s). Center of pressure measures were also recorded. The TD
      infants demonstrated significantly more phasic responses than the HR infants, who
      had more trials with tonic activity and more trials with no burst of muscle
      activity (Mann-Whitney U test, two-tailed, p=0.006). The TD infants demonstrated
      caudalcephalo, directionally appropriate recruitment patterns more often than the
      HR infants. There were some similarities between the two groups, with no
      significant difference between any of the center of pressure measures or onset
      latencies. Results suggest that postural development in HR infants with motor
      delays is complex. Some elements of seated postural control appear to be
      developmentally appropriate, e.g. presence of phasic activity in directionally
      appropriate muscles sequenced in a caudalcephalo pattern. However, frequency of
      these age appropriate responses was significantly lower in HR infants, who
      demonstrated many normal, albeit immature, responses, such as cephalocaudally
      sequenced muscle activity.

PMID- 15473173
TI  - Anaerobic muscle performance of children after long-term recovery from Guillain
      Barre syndrome.
AB  - The aim of this study was to evaluate anaerobic muscle performance in children
      after long-term recovery from Guillain-Barre syndrome (GBS). Participants were
      recruited from all children and adolescents with GBS admitted to The Hospital for
      Sick Children, University of Toronto, Canada, between 1988 and 1995. We assessed
      17 children (nine males, eight females; mean age at GBS diagnosis 7 years 11
      months, SD 4 years 2 months; mean age at testing 14 years 1 month) more than two
      years after acute GBS. Participants completed the Wingate anaerobic test to
      evaluate mean and peak muscle power. For mean arm muscle power (mean 47.5% [SD
      17.4%] of normal), only two participants were in the normal range. For mean leg
      muscle power (mean 83% [SD 28.3%] of normal), 15 participants were in the normal
      range. For arm peak power (mean 92.6% [SD 20.7%] of normal), 12 participants were
      in the normal range. For leg peak power (mean 116.3% of normal, SD 15.8%), all
      participants were in the normal range. Detailed manual muscle testing with the
      modified Medical Research Council scale was done on 34 muscle groups. Data were
      pooled to give a mean arm and leg muscle strength score (9.7, SD 0.30 and 9.4, SD
      0.50 respectively). Pearson's correlations of muscle endurance with arm and leg
      strength were not significant. Children with GBS have excellent long-term
      recovery of peak muscle power. Muscle endurance, measured by mean muscle power,
      was normal in the legs but markedly low in the arms. Pediatric rehabilitation
      programs after GBS should specifically target endurance of arm muscles.

PMID- 15473174
TI  - Joubert syndrome: long-term follow-up.
AB  - Twenty-nine patients (16 males, 13 females) with Joubert syndrome were identified
      from ophthalmology, neurology, and genetic databases covering a 15-year period at
      Great Ormond Street Hospital, London. Criteria for diagnosis included absent or
      markedly hypoplastic cerebellar vermis, abnormal eye movements, and developmental
      delay. Five patients had died. Scans and notes were available for 22 patients,
      and 18 cases were clinically reviewed. The median age was 10 years 10 months
      (range 3mo to 19y) and the median follow-up was 8 years 5 months (range 3mo to
      19y, with one new patient seen at 3mo of age). Cerebellar vermis
      hypoplasia/aplasia with 'molar tooth sign' in the axial plane was present in 22
      of 22 patients, coloboma in 6 of 22, and polydactyly in 6 of 22. In the 18
      clinically reviewed, apnoea occurred in 13 patients. Five had renal problems with
      cysts and 4 of 5 had abnormal electroretinograms (ERGs). Visual electrophysiology
      was abnormal in 14 of 18 patients, and in 6 there was evidence of deterioration
      in the ERG. Blood investigations of organic acids, phytanic acid, very-long-chain
      fatty acid, and transferrin were normal in 12 patients tested. Developmental
      assessment showed that 6 of 15 patients aged more than 5 years were at mainstream
      school, and 12 of 18 had started walking between 22 months and 10 years. Speech
      difficulties and behavioural problems were prominent.

PMID- 15473175
TI  - Coordination of suck-swallow-respiration in infants born to mothers with drug
      abuse problems.
AB  - To delineate quantitatively differences in suck-swallow-respiration coordination
      during feeding in term infants exposed to drugs in utero, 16 control infants (10
      females, six males; mean birthweight 3209g, standard error of the mean [SEM]
      103g) and 15 drug-exposed infants (seven females, eight males; seven cocaine,
      eight opiates; neonatal abstinence [Finnegan] scores less than 10; mean
      birthweight 3001g, SEM 93g) were studied in the first three days of life and
      again at one month of age. Coefficients of variation (COVs) of suck-suck, swallow
      swallow, and breath-breath intervals were used as measures of stability of
      individual rhythms. COVs of suck-swallow and swallow-breath intervals were used
      to determine stability of multiply integrated rhythms. In the first three days of
      life, a significantly higher percentage of 'apneic swallows' (runs of three or
      more swallows not associated with breathing movements, divided by total run
      swallows) was noted during feeding in the drug-exposed infants (mean 5.3% SEM
      1.7%) compared with controls (mean 0.9%, SEM 0.4%;p<0.02), who also had less
      breath-breath rhythmic stability (higher COV) and shorter swallow-breath
      intervals. These differences were no longer evident at one month of age. Opiate
      exposed infants were generally more affected than the cocaine-exposed infants.
      Swallowing was less rhythmic in the drug-exposed cohort, especially in opiate
      exposed infants, but this difference also disappeared by one month. In the first
      days of life, drug-exposed infants were less efficient feeders, ingesting less
      volume per run-swallow than controls (mean 0.31ml, SEM 0.05ml, versus 0.45ml, SEM
      0.05ml;p<0.05). The decreased efficiency appeared to be compensated for by a
      slightly faster swallow rate (mean 53 swallows per minute SEM 2 versus 47
      swallows per min, SEM 1, in controls;p<0.005). By one month of age these
      differences between groups had disappeared as well. Intrauterine drug exposure,
      even in infants with relatively mild symptoms of withdrawal, may adversely impact
      development of brainstem respiratory and swallow centers, thus affecting, albeit
      transiently, the underlying biorhythms of feeding.

PMID- 15473176
TI  - Rolling over in infants: age, ethnicity, and cultural differences.
AB  - A preliminary cross-sectional study of 72 Hong Kong Chinese infants suggested
      that these infants learn to roll from supine-to-prone before rolling from prone
      to-supine i.e. the opposite to teaching in most western texts. Three-hundred and
      sixty mothers were recruited postpartum and asked to record, on a chart,
      information related to the developmental milestone of rolling over for their
      infants (49% male) during the next 9 months. Telephone reminders were given at 4
      and 8 months and, by the end of the study, information had been obtained from 240
      mothers (67% of original sample, 51% male infants). Mean ages of rolling over
      were 5.1 months (SD1.5) for supine-to-prone and 5.7 months (SD1.3) for prone-to
      supine. Age of rolling over from supine-to-prone was not influenced by usual
      sleep position, infant's sex, mother's intention to breastfeed infant, number of
      siblings, marital status, main daytime caregiver, or feeding method over 9
      months. Hong Kong Chinese infants roll from supine-to-prone before they roll from
      prone-to-supine.

PMID- 15473177
TI  - Pyruvate dehydrogenase deficiency presenting as dystonia in childhood.
AB  - Two individuals with pyruvate dehydrogenase (PDH) deficiency due to missense
      mutations in the gene for the E1alpha subunit (PDHA1) presented during childhood
      with dystonia. The first patient, a male, presented at age 4 years with dystonia
      affecting the lower limbs, which responded to treatment with combined carbidopa
      and levodopa. The second patient, a female, was first investigated at age 6 years
      because of a dystonic gait disorder. In both patients, the main clue to the
      biochemical diagnosis was a raised concentration of lactate in the cerebrospinal
      fluid. PDH activity was significantly reduced in cultured fibroblasts in both
      cases. Dystonia is a previously unrecognized major manifestation of PDH
      deficiency and is of particular interest as the mutations in the PDHA1 gene in
      these patients have both been identified previously in individuals with typical
      presentations of the condition.

PMID- 15473178
TI  - Paradoxical embolism in a preterm infant.
AB  - Cerebral paradoxical embolism has not until now been described as a cause of
      cryptogenic stroke in newborn infants. A male infant was born at 27 weeks 2 days'
      gestational age by emergency Caesarean section in a twin pregnancy because of
      intrauterine growth retardation and absence of diastolic flow in the twin. His
      birthweight was 950g (50th centile). Apgar scores were 7 and 8 at 1 and 5 minutes
      respectively. At 17 days of life he showed sudden respiratory distress and signs
      of encephalopathy. Presence of deep venous thrombosis, patent foramen ovale
      (PFO), and clinical progression suggested paradoxical embolism which were
      confirmed by neuroradiological findings. The high incidence of PFO and central
      venous catheter-related deep venous thrombosis in newborn infants suggest that
      paradoxical embolism is probably a more common complication than has been
      thought.

PMID- 15473179
TI  - Giant axonal neuropathy.

PMID- 15473180
TI  - 'Visual impairment in children with brain damage'.

PMID- 15473181
TI  - Comprehensive care is put to the test in CMS demo.

PMID- 15473182
TI  - Efforts to deal with healthcare disparities gaining momentum.
AB  - Tackle disparities in health care now. Why? Because chronic disease impacts a
      disproportionate percentage of minority populations, and numerous well-documented
      studies show that minority groups are not getting the same level of quality or
      access as white Americans. Further, it's virtually impossible to take on
      escalating costs in any meaningful way without addressing disparities. Find out
      how some innovative organizations are making headway against this complicated
      problem.

PMID- 15473183
TI  - New tools capitalize on telehealth opportunities.
AB  - Introducing the 'telehealth pathway.' With the increasing amount of care
      management being conducted over the phone, it seems only logical that pathways
      would be developed to guide clinicians in this process. Find out how this new
      tool can help care managers reach more patients in a limited amount of time, and
      where developers believe it can have the biggest impact.

PMID- 15473184
TI  - Get physicians on board with information and incentives.
AB  - Creating a physician-friendly approach to DM. It's a 'must' if you want to
      achieve optimal results, but getting physicians on board a DM initiative is no
      easy task. Find out how one Pennsylvania-based plan has gradually won its
      provider network over by streamlining its DM offerings, sharing claims and
      performance data, and offering one-on-one assistance to practices that want to
      improve.

PMID- 15473185
TI  - The rising cost of food and beverages.

PMID- 15473186
TI  - It's almost budget time.

PMID- 15473187
TI  - Nutrition in the Caribbean.

PMID- 15473188
TI  - Inpatient metabolic control improves patient outcomes.

PMID- 15473189
TI  - Obesity: soon to be the no. 1 challenge for health care providers.

PMID- 15473190
TI  - Phony weight-loss claims: how to fight back.

PMID- 15473191
TI  - The search for quick and easy measures to combat obesity.

PMID- 15473192
TI  - Portuguese culture and nutrition.

PMID- 15473193
TI  - Direct current electrical conduction block of peripheral nerve.
AB  - Electrical currents can be used to produce a block of action potential conduction
      in whole nerves. This block has a rapid onset and reversal. The mechanism of
      electrical nerve conduction block has not been conclusively determined, and
      inconsistencies appear in the literature regarding whether the block is produced
      by membrane hyperpolarization, depolarization, or through some other means. We
      have used simulations in a nerve membrane model, coupled with in vivo
      experiments, to identify the mechanism and principles of electrical conduction
      block. A nerve simulation package (Neuron) was used to model direct current (dc)
      block in squid, frog, and mammalian neuron models. A frog sciatic
      nerve/gastrocnemius preparation was used to examine nerve conduction block in
      vivo. Both simulations and experiments confirm that depolarization block requires
      less current than hyperpolarization block. Dynamic simulations suggest that block
      can occur under both the real physical electrode as well as adjacent virtual
      electrode sites. A hypothesis is presented which formulates the likely types of
      dc block and the possible block current requirements. The results indicate that
      electrical currents generally produce a conduction block due to depolarization of
      the nerve membrane, resulting in an inactivation of the sodium channels.

PMID- 15473194
TI  - Producing preferred format material from Microsoft Word.
AB  - This paper presents a set of tools that are integrated with a word processor to
      produce documents in a visually impaired person's "preferred format." The paper
      considers the motivation for producing such tools and describes tools to perform
      spoken transcription (to cassette tape) and intelligent large print production.

PMID- 15473195
TI  - Conversion of EEG activity into cursor movement by a brain-computer interface
      (BCI).
AB  - The Wadsworth electroencephalogram (EEG)-based brain-computer interface (BCI)
      uses amplitude in mu or beta frequency bands over sensorimotor cortex to control
      cursor movement. Trained users can move the cursor in one or two dimensions. The
      primary goal of this research is to provide a new communication and control
      option for people with severe motor disabilities. Currently, cursor movements in
      each dimension are determined 10 times/s by an empirically derived linear
      function of one or two EEG features (i.e., spectral bands from different
      electrode locations). This study used offline analysis of data collected during
      system operation to explore methods for improving the accuracy of cursor
      movement. The data were gathered while users selected among three possible
      targets by controlling vertical [i.e., one-dimensional (1-D)] cursor movement.
      The three methods analyzed differ in the dimensionality of the cursor movement [1
      D versus two-dimensional (2-D)] and in the type of the underlying function
      (linear versus nonlinear). We addressed two questions: Which method is best for
      classification (i.e., to determine from the EEG which target the user wants to
      hit)? How does the number of EEG features affect the performance of each method?
      All methods reached their optimal performance with 10-20 features. In offline
      simulation, the 2-D linear method and the 1-D nonlinear method improved
      performance significantly over the 1-D linear method. The 1-D linear method did
      not do so. These offline results suggest that the 1-D nonlinear or the 2-D linear
      cursor function will improve online operation of the BCI system.

PMID- 15473196
TI  - Computer control using human intracortical local field potentials.
AB  - We describe the use of human cortical control signals to operate two assistive
      technology tools--a virtual keyboard speller and a computer-simulated digit. The
      cortical signals used for control are local field potentials recorded through an
      implanted neurotrophic electrode. In this system, the patients' cortical signals
      are transmitted wirelessly to a receiver and translated by computer software into
      either a computer cursor movement (for the virtual keyboard) or flexion of a
      cyber digit on a virtual hand. This report focuses on the progress of two
      subjects toward effective use of their "virtual" neuro-prosthetic devices to meet
      their assistive technology needs.

PMID- 15473197
TI  - Acute peripheral nerve recording characteristics of polymer-based longitudinal
      intrafascicular electrodes.
AB  - We examined the recording characteristics of two different types of polymer-based
      longitudinal intrafascicular electrodes (LIFEs) in peripheral nerve: single
      stranded (s-polyLIFEs) and multistranded (m-polyLIFEs). Recordings were also made
      from Pt-Ir wire-based electrodes (PtIrLIFEs) as a control. The electrodes were
      implanted in either tibial or medial gastrocnemius branches of the rabbit sciatic
      nerve, and in the sciatic nerve of rats. Recorded neural activity induced by
      manually elicited afferent neural activity showed that both polyLIFE versions
      performed comparably to PtIrLIFEs.

PMID- 15473198
TI  - A two-input sliding-mode controller for a planar arm actuated by four pneumatic
      muscle groups.
AB  - Multiple-input sliding-mode techniques are applied to a planar arm actuated by
      four groups of pneumatic muscle (PM) actuators in opposing pair configuration.
      The control objective is end-effector tracking of a desired path in Cartesian
      space. The inputs to the system are commanded input pressure differentials for
      the two opposing PM groups. An existing model for the muscle is incorporated into
      the arm equations of motion to arrive at a two-input, two-output nonlinear model
      of the planar arm that is affine in the input and, therefore, suitable for
      sliding-mode techniques. Relationships between static input pressures are derived
      for suitable arm behavior in the absence of a control signal. Simulation studies
      are reported.

PMID- 15473200
TI  - Too few to care.

PMID- 15473199
TI  - Detecting postural responses to sinusoidal sensory inputs: a statistical
      approach.
AB  - A common way for understanding sensory integration in postural control is to
      provide sinusoidal perturbations to the sensory systems involved in balance.
      However, not all subjects exhibit a response to the perturbation. Determining
      whether or not a response has occurred is usually done qualitatively, e.g., by
      visual inspection of the power spectrum. In this paper, we present the
      application of a statistical test for quantifying whether or not a postural sway
      response is present. The test uses an F-statistic for determining if there is
      significant power in postural sway data at the stimulus frequency. In order to
      describe the application of this method, 20 subjects viewed sinusoidal anterior
      posterior (A-P) optic flow at 0.1 and 0.25 Hz, while their A-P head translation
      was measured. The test showed that significant postural responses were detected
      at the stimulus frequency in 12/20 subjects at 0.1 Hz and 13/20 subjects at 0.25
      Hz.

PMID- 15473201
TI  - Deconstructing nursing from practice to theory.
AB  - People often talk about 'basic' nursing care as if it is the simplest thing in
      the world: it looks so easy that anyone could do it. But there is more to it than
      meets the eye. We asked three prominent nurses to spend time watching individual
      nurses going about their business in an attempt to get to the bottom of this
      thing called nursing care. And when you look beyond the surface it is obvious
      delivering nursing care is neither simple nor basic.

PMID- 15473202
TI  - Caribbean horizons.

PMID- 15473203
TI  - After the volcano. Interview by Lynne Wallis.

PMID- 15473204
TI  - Beating the media frenzy.

PMID- 15473205
TI  - Crossroads of infection.

PMID- 15473206
TI  - Flu jab better than cure.

PMID- 15473207
TI  - Pay modernisation and healthcare governance.
AB  - Policies interact and have direct and indirect consequences resulting in both
      short-term and longer-term effects on the working lives of professionals, the
      care they offer and the education needed by future generations of staff. This
      article explores how pay modernisation could result in benefits and risks for
      corporate, clinical and staff governance. It is argued that if pay modernisation
      as a major enabler of service redesign is to succeed then far greater
      understanding of how various policies interact and their potential consequences
      is required.

PMID- 15473208
TI  - The value of qualitative research.
AB  - This article describes the dual nature of nursing research. It describes how
      qualitative research can present the patient's experience in a way that
      quantitative research cannot, but warns against over-reliance on qualitative
      methods. The article critically summarises the ideas of the European philosophers
      on which qualitative research is based.

PMID- 15473209
TI  - Irritable bowel syndrome: assessment and management.
AB  - In this article the author discusses irritable bowel syndrome--a chronic,
      debilitating and functional disorder. The management of irritable bowel syndrome
      is based on treating the symptoms, rather than cure. Nurses in both hospital and
      community settings are in a good position to provide support, information and
      continuity of care for patients with this condition.

PMID- 15473210
TI  - Mentoring: the key to clinical learning.

PMID- 15473211
TI  - What strategies are nurses using to overcome communication barriers?

PMID- 15473212
TI  - Do our nonverbal messages inhibit patient care?

PMID- 15473213
TI  - AstraZeneca: setting the standard for cancer treatment, awareness, and education.

PMID- 15473214
TI  - Web-based tools can help to improve health literacy.

PMID- 15473215
TI  - ONS flexes its political muscles at annual leadership weekend.

PMID- 15473216
TI  - By examining what is, we can determine what can be.

PMID- 15473217
TI  - Perinatal outcomes with the antepartum diagnosis of cystic hygroma.
AB  - OBJECTIVE: To describe antenatal diagnosis and clinical outcomes of fetal cystic
      hygroma. STUDY DESIGN: Retrospective case series derived from ultrasound
      database. Diagnoses were made from July 2000 through January 2003. RESULTS:
      Twenty-five fetuses were identified with cystic hygroma. Median gestational age
      at diagnosis was 17.3 weeks. Posterior nuchal cystic hygromas accounted for 21
      (84%) cases, while two (8%) were axillary, and one each in the anterior neck and
      buttock. Additional abnormalities were noted in twenty (80%) fetuses; most common
      were non-immune hydrops (12/25, 48%) and cardiac defects (5/25, 20%). Eighteen
      patients (72%) underwent amniocentesis and ten were aneuploid. Six fetuses (25%)
      sustained intrauterine fetal demise and nine (38%) patients sought therapeutic
      termination. Nine infants (38%) were liveborn, but only six (25%) survived the
      neonatal period. CONCLUSIONS: Antenatal diagnosis of fetal cystic hygroma heralds
      an extremely poor perinatal prognosis. Associated abnormalities were noted in 80%
      of fetuses with a significant incidence of aneuploidy. Targeted ultrasonography
      and extensive counseling of parents is recommended.

PMID- 15473218
TI  - A case report of warm weather accidental hypothermia.
AB  - A case of hypothermia is presented as a reminder to "Deep South" physicians that
      our warm weather is not prophylaxis against this syndrome; and many common
      situations, diseases and medications contribute to and worsen the condition.
      Diagnosis is made by obtaining a true core body temperature and effective
      treatment modalities can be easily applied. With appropriate rewarming, a search
      for complications and monitoring of patient progress a gratifying outcome should
      result for both patient and physician.

PMID- 15473219
TI  - Heart to get along with.

PMID- 15473220
TI  - "They said they would stay"--physician work force.

PMID- 15473221
TI  - Medical ethics: charting a new course.

PMID- 15473222
TI  - A rational method for controlling the spread of venereal disease in 1904. 1904.

PMID- 15473223
TI  - The causes of childhood obesity: who or what is responsible?

PMID- 15473224
TI  - One year after the JNC-7: lessons for renal care.

PMID- 15473225
TI  - Cell phone use in the dialysis clinic: is it time to review?

PMID- 15473226
TI  - Qualified technicians round out the multidisciplinary renal team.

PMID- 15473227
TI  - Medical and legal issues for risk management in a dialysis facility.

PMID- 15473228
TI  - Vitamin B12. A review.

PMID- 15473229
TI  - NN&I workload and compensation survey/Part 3--Patient assessment, documentation,
      and communication issues.

PMID- 15473230
TI  - Home dialysis. Time to revisit the opportunity.
AB  - Home dialysis is not for everyone, but it should be considered more seriously by
      renal providers as the industry struggles to improve outcomes while lowering
      costs. Changes in the nephrologist MCP this year and the MMA changes to provider
      reimbursement coming in 2005 are reprioritizing the parameters for reimbursement.
      Barriers that prevent patients from maintaining or returning to work are being
      minimized. All these changes should cause the nephrologists and providers to take
      a moment and re-evaluate the home dialysis therapies. We as a community should
      continue to pressure Medicare and Congress to provide pre-dialysis education and
      support. The bottom line is improved patient outcomes and lower overall cost of
      care when patients are at home for their therapies.

PMID- 15473231
TI  - Fatigue--the enemy of good patient care.

PMID- 15473232
TI  - Optimization of diffraction grating profiles in fabrication by electron-beam
      lithography.
AB  - We propose a new design method for periodic diffraction gratings to be fabricated
      with direct-writing electron-beam lithography. When the grating has a small
      period, the proximity effect of electron scattering restricts the grating profile
      after developing. Our design method optimizes the electron-dose profile and
      grating profile simultaneously to obtain the desired diffraction efficiency under
      the restriction of the proximity effect. The optimization is made with rigorous
      electromagnetic grating analysis and the resist development simulator. When we
      designed the diffraction grating with a period of 1.0 microm to obtain the
      highest efficiency of the first-order diffracted light of a 633-nm wavelength,
      the calculated grating profile was really different from the profile optimized
      only with rigorous electromagnetic grating analysis. Moreover, the diffraction
      grating of the electron-beam resist was fabricated according to the simulation
      result. The estimated diffraction efficiency was 82%, and the measured efficiency
      was 70%.

PMID- 15473233
TI  - Design of a nonnull interferometer for aspheric wave fronts.
AB  - The presence of highly aspheric wave fronts in an interferometer leads to a need
      for system calibration, and this calibration requirement affects the design of
      the interferometer. Dynamic range, vignetting, and the ability to characterize
      components all must be considered during the design stages. The interferometer
      must be designed with respect to wave-front propagation as opposed to reference
      sphere aberrations. A nonnull interferometer for measurement of aspheric
      transmitted wave fronts has been developed, and the design process is described.
      Transmitted wave fronts for a conformal window and a progressive-addition bifocal
      lens have been measured to demonstrate the applicability of the system to
      aspheric testing.

PMID- 15473234
TI  - Iterative reverse optimization procedure for calibration of aspheric wave-front
      measurements on a nonnull interferometer.
AB  - The accuracy of interferometric measurements made with a nonnull configuration is
      degraded by test-dependent aberrations. Calibration of the data can be done with
      reverse optimization methods. An iterative reverse optimization process that
      improves efficiency and eliminates sensitive merit function weighting issues is
      described. The process is shown to calibrate a nonnull interferometric
      measurement of a wave front with more than 200 waves of departure to an accuracy
      of 0.16 waves peak to valley and 0.02 waves rms.

PMID- 15473235
TI  - Wavelength response of waveguide volume grating couplers for optical
      interconnects.
AB  - The wavelength response of a waveguide volume grating coupler (WVGC) is analyzed
      for coupling light from a slab waveguide into the superstrate. A leaky-mode
      approach is used in conjunction with rigorous coupled-wave analysis. A
      quantitative theoretical study of the effect of index modulation, waveguide
      index, and grating thickness on the wavelength bandpass of a WVGC is also
      presented. The FWHM wavelength bandpasses found for high-efficiency couplers
      range from 173 to 525 nm. The various Bragg conditions that can be used in
      designing a WVGC are also presented and compared. The use of the propagation
      constant of the mode being outcoupled as the incident wave vector in the Bragg
      condition is shown to produce the highest coupling efficiency.

PMID- 15473236
TI  - Far-field expression of a high-power laser diode.
AB  - Based on the off-axis theory, a model for describing the far field with the
      bipeak structure of a high-power laser diode is proposed. The computed results
      agree well with the measured far-field data of practical devices. A minimum
      overall error criterion for fitting the theoretical model with the measured data
      is also given. The results show that the overall error of this model is less than
      5% for popular laser diodes. This model has a simple mathematical structure and
      can be easily used to design the beam-shaping system and to analyze the
      propagation properties when the laser beam passes through an optic system.

PMID- 15473237
TI  - Simultaneous two-photon spectral and lifetime fluorescence microscopy.
AB  - When a fluorescence photon is emitted from a molecule within a living cell it
      carries a signature that can potentially identify the molecule and provide
      information on the microenvironment in which it resides, thereby providing
      insights into the physiology of the cell. To unambiguously identify fluorescent
      probes and monitor their physiological environment within living specimens by
      their fluorescent signatures, one must exploit as much of this information as
      possible. We describe the development and implementation of a combined two-photon
      spectral and lifetime microscope. Fluorescence lifetime images from 16 individual
      wavelength components of the emission spectrum can be acquired with 10-nm
      resolution on a pixel-by-pixel basis. The instrument provides a unique
      visualization of cellular structures and processes through spectrally and
      temporally resolved information and may ultimately find applications in live cell
      and tissue imaging.

PMID- 15473238
TI  - Analysis of a cylindrical microlens array with long focal depth by a rigorous
      boundary-element method and scalar approximations.
AB  - We investigated the focal characteristics of open-regional cylindrical microlens
      arrays with long focal depth by using a rigorous boundary-element method (BEM)
      and three scalar methods, i.e., a Kirchhoff and two Rayleigh-Sommerfeld
      diffraction integral forms. Numerical analysis clearly shows that the model
      cylindrical microlens arrays with different f-numbers can generate focusing beams
      with both long focal depth and high transverse resolution. The performance of the
      cylindrical microlens arrays, such as extended focal depth, relative extended
      focal depth, diffraction efficiency, and focal spot size, is appraised and
      analyzed. From a comparison of the results obtained by the rigorous BEM and by
      scalar approximations, we found that the results are quite similar when the f
      number equals f/1.6; however, they are quite different for f/0.8. We conclude
      that the BEM should be adopted to analyze the performance of a microlens array
      system whose f-number is less than f/1.0.

PMID- 15473239
TI  - Liquid-crystal blazed grating with azimuthally distributed liquid-crystal
      directors.
AB  - We propose a novel formation method of arbitrary phase profiles of circular light
      by controlling azimuthal angles of liquid-crystal directors; its principle is
      described theoretically. A new liquid-crystal blazed grating is demonstrated by
      use of the proposed method. It is revealed that the first-order diffraction
      efficiency reaches the maximum value (theoretically 100%, experimentally
      approximately 90%) at an optimum applied voltage when the phase difference
      between the extraordinary and ordinary rays agrees with one-half the wavelength.
      Furthermore, the polarization states of the diffracted light beams are analyzed
      by Stokes parameter measurements, and unique polarization-splitting properties
      are revealed.

PMID- 15473240
TI  - Quadratic correlation filter design methodology for target detection and
      surveillance applications.
AB  - A novel method is presented for optimization of quadratic correlation filters
      (QCFs) for shift-invariant target detection in imagery. The QCFs are quadratic
      classifiers that operate directly on the image data without feature extraction or
      segmentation. In this sense, the QCFs retain the main advantages of conventional
      linear correlation filters while offering significant improvements in other
      respects. For example, multiple correlators work in parallel to optimize jointly
      the QCF performance metric and produce a single combined output, which leads to
      considerable simplification of the postprocessing scheme. In addition, QCFs also
      yield better performance than their linear counterparts for comparable throughput
      requirements. The primary application considered is target detection in infrared
      imagery for surveillance applications. In the current approach, the class
      separation metric is formulated as a Rayleigh quotient that is maximized by the
      QCF solution. It is shown that the proposed method results in considerable
      improvement in performance compared with a previously reported QCF design
      approach and many other detection techniques. The results of independent tests
      and evaluations at the U.S. Army's Night Vision Laboratory are also presented.

PMID- 15473241
TI  - Fourier fringe processing by use of an interpolated Fourier-transform technique.
AB  - Recently a powerful Fourier transform technique was introduced that was able to
      extract the phase from only one image. However, because the method is based on
      the two-dimensional Fourier transform, it inherently suffers from leakage
      effects. A novel procedure is proposed that does not exhibit this distortion. The
      procedure uses localized information and estimates both the unknown frequencies
      and the phases of the fringe pattern (using an interpolated fast Fourier
      transform method). This allows us to demodulate the fringe pattern without any
      distortion. The proposed technique is validated on both computer simulations and
      the profile measurements of a tube.

PMID- 15473242
TI  - Broadband volume holographic imaging.
AB  - We demonstrate transmission geometry volume holograms working under broadband
      illumination. We show that increased illumination bandwidth enhances the lateral
      field of view of planar reference holograms. We exploit this phenomenon to design
      volume holographic spectrum analyzers and present results from an experimental
      prototype. Furthermore, we show that there is a trade-off involved, because an
      improvement in the field of view results in a reduction of image contrast as a
      function of depth. We experimentally demonstrate this trade-off and discuss
      possible ways to overcome it.

PMID- 15473243
TI  - Irregular repeat-accumulate codes for volume holographic memory systems.
AB  - We investigate the application of irregular repeat-accumulate (IRA) codes in
      volume holographic memory (VHM) systems. We introduce methodologies to design
      efficient IRA codes. We show that a judiciously designed IRA code for a typical
      VHM can be as good as the optimized irregular low-density-parity-check codes
      while having the additional advantage of lower encoding complexity. Moreover, we
      present a method to reduce the error-floor effect of the IRA codes in the VHM
      systems. This method explores the structure of the noise pattern in holographic
      memories. Finally, we explain why IRA codes are good candidates for the VHM
      systems.

PMID- 15473244
TI  - Rigorous comparison of parabolically tapered and conventional multimode
      interference-based 3-dB power splitters in InGaAsP/InP waveguides.
AB  - Design issues such as optical transmission, interference mechanisms, the
      splitting ratio, the polarization dependence, and the fabrication tolerances of a
      compact parabolically tapered multimode-interference (MMI)-based 3-dB power
      splitter on an InP-based deeply etched ridge waveguide, by use of the finite
      element-based beam-propagation method, are presented. The benefits and drawbacks
      of the use of the tapered structure, in comparison with an untapered MMI-based 3
      dB splitter, have also been investigated.

PMID- 15473245
TI  - Efficient, reliable, long-lifetime, diode-pumped Nd:YAG laser for space-based
      vegetation topographical altimetry.
AB  - A highly efficient, diode-pumped, Nd:YAG laser is described. The oscillator
      utilizes an unstable resonator design with a Gaussian reflectivity output coupler
      and a side-pumped zigzag slab gain medium. The laser produces 18-mJ, 10-ns pulses
      at a repetition rate of 242 Hz in a near-TEM00 mode with an optical efficiency of
      up to 14%. An extended performance test was recently concluded in which the
      transmitter operated at reduced output for more than 4.8 x 10(9) shots with no
      optical damage. Design criteria, beam quality, and lifetime data are presented.

PMID- 15473246
TI  - Spatial and temporal dependence of interspark interactions in femtosecond
      nanosecond dual-pulse laser-induced breakdown spectroscopy.
AB  - A femtosecond air spark has recently been combined with a nanosecond ablative
      pulse in order to map the spatial and temporal interactions of the two plasmas in
      femtosecond-nanosecond orthogonal preablation spark dual-pulse laser-induced
      breakdown spectroscopy (LIBS). Good spatial and temporal correlation was found
      for reduced atomic emission from atmospheric species (nitrogen and oxygen) and
      increased atomic emission from ablated species (copper and aluminum) in the
      femtosecond-nanosecond plasma, suggesting a potential role for atmospheric
      pressure or nitrogen/oxygen concentration reduction following air spark formation
      in generating atomic emission enhancements in dual-pulse LIBS.

PMID- 15473247
TI  - Fluorescence correlation spectroscopy: incorporation of probe volume effects into
      the three-dimensional Gaussian approximation.
AB  - Fluorescence correlation spectroscopy is a valuable tool in many scientific
      disciplines. In particular, such a spectroscopic technique has received a great
      deal of attention because of its remarkable potential for single-molecule
      detection. It is understood, however, that quantitative measurements can be
      considered reliable as long as molecular photophysics has been well
      characterized. To that end, molecular saturation and probe volume effects, which
      can worsen experimental accuracy, are treated here. These phenomena are
      adequately incorporated into the well-known three-dimensional Gaussian
      approximation by a novel method applied to interpret saturated fluorescence
      signals [Opt. Lett. 28, 2016 (2003)]. Comparisons with literature data are given
      to show the improvements of the suggested method compared with other approaches.

PMID- 15473248
TI  - Time-resolved explosion dynamics of H2O droplets induced by femtosecond laser
      pulses.
AB  - Series of time-resolved still images of the explosion dynamics of micrometer
      sized water droplets after femtosecond laser-pulse irradiation were obtained for
      different laser-pulse intensities. Amplified pulses centered around a wavelength
      of 805 nm with 1-mJ energy and 60-fs duration were focused onto the droplet to
      initiate the dynamics. Several effects, such as forward and backward plumes,
      jets, water films, and shock waves, were investigated. Additionally, the
      influence of different pulse durations produced by chirping the laser pulses was
      observed.

PMID- 15473249
TI  - Ion channels as important targets for antiepileptic drug design.
AB  - Ion channels have a critical role in the function of the nervous system, where
      they instigate and conduct nerve impulses by asserting control over the voltage
      potential across the plasma membrane. Propagation of electrical impulses occurs
      by opening of voltage-gated ion channels. Ion channel blockers prevent this from
      occurring, and can therefore be used in the treatment of central nervous system
      disorders and neuropathic pain. Recent identification of ion channel gene
      mutations in Mendelian epilepsies suggests that genetically driven neuronal
      hyperexcitability plays an important role in epileptogenesis. Studies with animal
      seizure models have indicated that changes in temporal and spatial expression of
      voltage-gated sodium channels may be important in the pathology of epilepsy. This
      paper is aimed at elucidating the organization of the ion channels and covers a
      review on the antiepileptic drugs, both established and currently under
      development targeted to the ion channels in order to bring about effective
      seizure control.

PMID- 15473250
TI  - Neuroprotection against ischemic/hypoxic brain damage: blockers of ionotropic
      glutamate receptor and voltage sensitive calcium channels.
AB  - The growing number of cellular and molecular pathways believed to be involved in
      mechanisms of ischemic cell death in the brain has spurred a similar growth in
      the number of potential neuroprotective modalities, the majority of which are
      pharmacological in nature. Preventing or minimizing the first few steps in the
      cascade of events leading to ischemic cell death would have a more profound
      effect on the postischemic outcome than intervention at later steps in that
      cascade. This logic is, of course, at the heart of the urgency in providing the
      stroke or cardiac arrest patient with the earliest possible neuroprotective
      treatment. For the purpose of assessing potential neuroprotective modalities, the
      use of a well-established cerebral hypoxic/ischemic model system is a
      prerequisite. In our studies, we have used two major approaches, in vitro and in
      vivo. We evaluated both agonists and antagonists of ionotropic glutamate receptor
      channels (IGRC) and their effects in exacerbating and attenuating, respectively,
      the posthypoxic/ischemic outcome. Other drugs were tested for their ability to
      block the L-type voltage-sensitive calcium channels (VSCC), which are responsible
      for calcium influx and overload upon hypoxia/ischemia. These two membrane protein
      entities, the IGRC and the VSCC, are believed to be involved in the early stages
      of the cellular cascade that leads to the demise of neurons posthypoxia/ischemia.
      Some of the drugs were also tested for possible interaction with each other
      searching for possible synergy. These and other published studies in the field
      are reviewed here.

PMID- 15473251
TI  - Microglia-targeted pharmacotherapy in retinal neurodegenerative diseases.
AB  - Microglial cells, members of the monocytic lineage, represent the resident
      immunocompetent cells of the central nervous system including the retina with its
      peculiarities like a double blood retinal barrier. Microglial cells invade the
      retina in response to naturally occurring neuronal death during embryonic
      development and remodelling. Resident microglial cells are extremely sensitive to
      changes in their microenvironment arising from either traumatic or chronic
      neurodegeneration, inproper wiring, hereditary diseases or infection and become
      rapidly activated. In their activated state, the cells undergo drastic
      morphological changes, upregulate a variety of receptors and secrete soluble
      factors, which contribute to recognition and phagocytotic cleareance of dying or
      malfunctioning neurons. In this review, we aim to summarise the current knowledge
      of microglial involvement in experimentally induced or naturally occurring
      retinal neurodegenerations with emphasising on mechanisms of microglia
      activation. Expanding on the mechanisms, we shall discuss on approaches to
      pharmacologically interfere with the microglial activation and neurophagy. The
      protagonistic role of these cells in the outcome of certain diseases may help
      designing microglial targeted treatments with potential benefit for neuronal
      survival and regeneration in clinically relevant conditions.

PMID- 15473252
TI  - In vivo MRI in different models of experimental epilepsy.
AB  - In order to investigate epilepsy, that is one of the most common neurological
      disorders, in the last decades different animal models have been proposed.
      Prevention, diagnosis, treatment and basic knowledge have been improved by the
      mean of these models. Numerous animal models have been developed in epilepsy
      research, both for generalized and for simple/complex partial seizures. Animal
      models for generalized seizures include sensory (light, noise, movement, etc) or
      electrical stimulations and genetic models. Models for focal seizures include
      topical or systemic application of pro-convulsive compounds or electrical
      stimulation. Baboons, mice, rats, rabbits, and Fayoumi chicken have been
      extensively used in this regard. Since 1983, when magnetic resonance spectroscopy
      was used to evaluate for the first time in vivo alterations induced by status
      epilepticus in rabbit, an increasing interest for the neuroimaging perspective
      has led to new insights in the study of epileptic disorders. In the early 1990s
      experimental studies provided evidence for the feasibility of magnetic resonance
      imaging analysis and detection of tissue damage in kainic acid-induced epilepsy
      in rat. In the following years a wealth of data has been obtained by the mean of
      functional MRI and/or by diffusion-weighted images. The studies reported in the
      literature of the last decades indicate in vivo magnetic resonance of epilepsy
      model as valuable and extremely informative tool.

PMID- 15473253
TI  - Clinical pharmacotherapy for obesity: current drugs and those in advanced
      development.
AB  - The current obesity pandemic imposes a major global disease burden. Levels of non
      communicable diseases such as type 2 diabetes, cardiovascular disease and some
      cancers will continue to rise unless an effective approach to treat obesity is
      found. Sustained weight loss of between 5-10% in the obese, by various means,
      confers marked health benefits. The currently available pharmacotherapies,
      orlistat and sibutramine, can induce weight loss of between 5-10% over 2 years or
      more. In trials, orlistat and sibutramine induced weight loss tends to be only
      between 2-4 kg greater than that produced by placebo control. However, this
      additional placebo subtracted weight loss produces marked additional improvements
      in diabetes and cardiovascular risk factors. Moreover, in the 4 year long XENDOS
      trial, the modest placebo subtracted weight loss produced by orlistat (2.8 kg)
      reduced the incidence of diabetes by over a third in those with normal glucose
      tolerance, and by nearly half in those with impaired glucose tolerance. Despite
      this, prescription sales of sibutramine in the US have apparently remained static
      and those of orlistat have fallen, with the drug now entering the global over-the
      counter medication market. Recent data on potential anti-obesity drugs currently
      under going phase III trials, such as Rimonabant and Topiramate, demonstrate
      these drugs produce greater and more prolonged weight loss. Wider use of
      pharmacotherapy and enhanced efficacy for the next generation of anti-obesity
      drugs certainly promise to reduce obesity related illness if not halt the rise in
      obesity per se.

PMID- 15473254
TI  - Traumatic injury to CNS fiber tracts--what are the genes telling us?
AB  - In contrast to the peripheral nervous system (PNS) nerve fiber tracts of the
      adult central nervous system (CNS) cannot spontaneously regenerate in response to
      lesions. As a result injured individuals suffer from chronically impaired
      neuronal connections leading to major motor-, sensory- and cognitive deficits. It
      is generally assumed that combinatorial effects account for this regeneration
      failure including a growth non-permissive environment within CNS lesion zones as
      well as incomplete activation of axonal growth programmes. In order to design CNS
      repair strategies it is, therefore, imperative to address the molecular
      mechanisms responsible for this abortive growth behaviour by means of large scale
      screening techniques. This review summarizes the outcome of recent gene
      expression profiling studies investigating local and remote molecular reactions
      following CNS axotomy.

PMID- 15473255
TI  - Psychosocial conditions and the efficacy of clinically available anxiolytics.
AB  - The treatment of anxiety cannot be considered a solved problem, therefore,
      efforts are directed towards the development of novel treatment approaches.
      Increasing evidence suggests, however, that the efficacy of available treatments
      can be improved by taking into account the yet poorly known interactions between
      psychosocial conditions and the efficacy of pharmacological treatments. We review
      here evidence demonstrating that psychosocial factors affect the properties and
      function of receptors that mediate the effects of clinically available
      anxiolytics. Such neuronal changes affect the efficacy of anxiolytics, which
      consequently depends largely on psychosocial factors. We show that the
      interaction between psychosocial factors and drug responsiveness is clinically
      relevant. Laboratory studies predict that (i) the frequent exposure of subjects
      to acute stressors lowers the efficacy of benzodiazepines and buspirone, but
      increases the efficacy of selective serotonin reuptake inhibitors (SSRIs); (ii)
      the anxiolytic efficacy of buspirone is largely affected by social support and
      stability, whereas (iii) the efficacy of SSRIs is larger in subjects experiencing
      early maltreatment. Laboratory studies also show that the side effects of
      compounds decrease under certain conditions. Disparate human studies suggest that
      such predictions are clinically valid. Thus, further research on the relationship
      between psychosocial (Axis-IV) factors and drug efficacy would lead to
      substantial therapeutic progress with the available anxiolytic compounds. This
      interaction should be in focus also when new therapeutic approaches are
      developed.

PMID- 15473256
TI  - A promoter polymorphism in the central MHC gene, IKBL, influences the binding of
      transcription factors USF1 and E47 on disease-associated haplotypes.
AB  - The human major histocompatibility complex (MHC) contains genes that affect
      susceptibility to numerous immunopathological diseases. We propose that genes in
      the central MHC between TNFA and HLA-B explain associations between the 8.1
      haplotype (HLA-A1, B8, DR3) and disease. IKBL encodes a protein resembling
      members of the IkappaB protein family that regulate bioavailability of NFkappaB.
      We have identified two polymorphisms in the 500 bp upstream of the transcription
      start site of IKBL that distinguish the 8.1 haplotype from the resistant 7.1
      haplotype (HLA-A3, B7, DR15). A single nucleotide polymorphism at -62 disrupts a
      putative E-box binding sequence. To investigate binding of transcription factors
      in vitro, we exposed 32P-labeled DNA fragments carrying both alleles to nuclear
      extracts, showing allele-specific binding of nuclear proteins from Jurkat cells
      but not from other lineages. Supershift studies using Jurkat nuclear extract
      showed that the E-box protein, E47, and ubiquitously expressed transcription
      factor USF1 bind to the E-box element of the 7.1 haplotype. Transient
      transfections of luciferase reporter constructs carrying promoter alleles of IKBL
      into Jurkat cells showed an effect of IKBL-62 alleles. In contrast, alleles at 
      421 did not affect transcription factor binding or transcription. IKBL was
      expressed at low levels in Jurkat cells but not in blood mononuclear cells, and
      expression declined following mitogenic stimulation. The restriction of IKBL
      expression to Jurkat cells is consistent with evidence that E47 is expressed in
      thymocytes and suggests IKBL may affect autoimmunity through an effect on T-cell
      selection.

PMID- 15473258
TI  - Modulation of 3-hydroxy-3-methylglutaryl-CoA reductase gene expression by CuZn
      superoxide dismutase in human fibroblasts and HepG2 cells.
AB  - The homeostasis of intracellular cholesterol in animal cells is highly regulated
      by a complex system in which the microsomal rate-limiting enzyme 3-hydroxy-3
      methylglutaryl CoA (HMG-CoA) reductase plays a key role in cholesterol synthesis.
      Substantial evidence has demonstrated that the cytosolic antioxidant enzyme CuZn
      superoxide dismutase (SOD1) inhibits the HMG-CoA reductase activity in rat
      hepatocytes and in human fibroblasts by decreasing cholesterol synthesis.
      Although these data suggest that SOD1 exerts a physiological role in cholesterol
      metabolism, it is still unclear whether the decrease of HMG-CoA reductase
      activity is mediated by transcriptional or by posttranscriptional events. The
      results of the present study, obtained by one-step RT-PCR assay, demonstrated
      that both SOD1 and the metal-free form of enzyme (Apo SOD1) inhibit HMG-CoA
      reductase gene expression in hepatocarcinoma HepG2 cells, in normal human
      fibroblasts, and in fibroblasts of subjects affected by familiar
      hypercholesterolemia. Accordingly, SOD1 could be used as a potential agent in the
      treatment of hypercholesterolemia, even in subjects lacking a functional LDL
      receptor pathway.

PMID- 15473257
TI  - Expression of the peripheral benzodiazepine receptor triggers thymocyte
      differentiation.
AB  - In the thymus, during T-cell differentiation, the expression of the peripheral
      benzodiazepine receptor (PBR) modulates. The protein level decreases between the
      double negative and double positive stages, and then increases when thymocytes
      become single positive. We addressed the role played by PBR in T-cell maturation.
      To this aim, we used Jurkat cells, which are immature T lymphocytes derived from
      an acute lymphoblastic leukemia. These cells are PBR negative and were stably
      transfected to achieve PBR levels similar to that in mature T cells. Using the
      DNA chip technology, we analyzed the PBR expression-dependent gene changes and
      evidenced that PBR-expressing cells exhibited more mature features than mock
      transfected ones. A majority of the modulated genes encode proteins playing
      direct or indirect roles during the lymphocyte maturation process. In particular,
      PBR expression induced several differentiation markers (such as CD1, CD6), or key
      regulating elements (e.g., RAG1, RAG2, CD99, TCR). By contrast, some regulators
      of TCR signaling were reduced. PBR expression also affected the expression of
      critical apoptosis regulators: the proapoptotic lipocortin I, galectin-1, and
      galectin-9 were reduced while the antiapoptotic Bcl-2 was induced. Altogether our
      results supported the hypothesis that PBR controls T-cell maturation and
      suggested mechanisms through which PBR may regulate thymocyte-positive selection.

PMID- 15473259
TI  - Gene expression profiling of fibroblasts from a human progeroid disease
      (mandibuloacral dysplasia, MAD #248370) through cDNA microarrays.
AB  - Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder caused
      basically by a missense mutation within the LMNA gene, which encodes for lamin
      A/C. We have used gene expression profiling to characterize the specificity of
      molecular changes induced by the prevalent MAD mutation (R527H). A total of 5531
      transcripts expressed in human dermis were investigated in two MAD patients, both
      carrying the R527H mutation, and three control subjects (age and sex matched).
      Transcription profiles revealed a differential expression in MAD vs. control
      fibroblasts in at least 1992 genes. Sixty-seven of these genes showed a common
      altered pattern in both patients with a threshold expression level >+/-2.
      Nevertheless, a large number of these genes (43.3%) are ESTs or encode for
      protein with unknown function; the other genes are involved in biological
      processes or pathways such as cell adhesion, cell cycle, cellular metabolism, and
      transcription. Quantitative RT-PCR was applied to validate the microarray results
      (R2= 0.76). Analysis of the effect of the prevalent MAD mutation (R527H) over the
      transcriptional pattern of genes expressed in the human dermis showed that this
      LMNA gene mutation has pleiotropic effects on a limited number of genes. Further
      characterization of these effects might contribute to understanding the molecular
      pathogenesis of this disorder.

PMID- 15473261
TI  - Synthesis of chiral alpha-amino aldehydes linked by their amine function to solid
      support.
AB  - The anchoring of an alpha-amino-acid derivative by its amine function on to a
      solid support allows some chemical reactions starting from the carboxylic acid
      function. This paper describes the preparation of alpha-amino aldehydes linked to
      the support by their amine function. This was performed by reduction with LiAlH4
      of the corresponding Weinreb amide linked to the resin. The aldehydes obtained
      were then involved in Wittig or reductive amination reactions. In addition, the
      linked Weinreb amide was reacted with methylmagnesium bromide to yield the
      corresponding ketone. After cleavage from the support, the compounds were
      obtained in good to excellent yields and characterized.

PMID- 15473260
TI  - Global analysis of HuR-regulated gene expression in colon cancer systems of
      reducing complexity.
AB  - HuR, a protein that binds to target mRNAs and can enhance their stability and
      translation, is increasingly recognized as a pivotal regulator of gene expression
      during cell division and tumorigenesis. We sought to identify collections of HuR
      regulated mRNAs in colon cancer cells by systematic, cDNA array-based assessment
      of gene expression in three systems of varying complexity. First, comparison of
      gene expression profiles among tumors with different HuR abundance revealed
      highly divergent gene expression patterns, and virtually no changes in previously
      reported HuR target mRNAs. Assessment of gene expression patterns in a second
      system of reduced complexity, cultured colon cancer cells expressing different
      HuR levels, rendered more conserved sets of HuR-regulated mRNAs. However, the
      definitive identification of direct HuR target mRNAs required a third system of
      still lower complexity, wherein HuR-RNA complexes immunoprecipitated from colon
      cancer cells were subject to cDNA array hybridization to elucidate the endogenous
      HuR-bound mRNAs. Comparison of the transcript sets identified in each system
      revealed a strikingly limited overlap in HuR-regulated mRNAs. The data derived
      from this systematic analysis of HuR-regulated genes highlight the value of low
      complexity, biochemical characterization of protein-RNA interactions. More
      importantly, however, the data underscore the broad usefulness of integrated
      approaches comprising systems of low complexity (protein-nucleic acid) and high
      complexity (cells, tumors) to comprehensively elucidate the gene regulatory
      events that underlie biological processes.

PMID- 15473262
TI  - Tissue distribution of antihypertensive dipeptide, Val-Tyr, after its single oral
      administration to spontaneously hypertensive rats.
AB  - The distribution of an antihypertensive dipeptide, Val-Tyr (VY), in the tissues
      of spontaneously hypertensive rats (SHR) was investigated in this study. A single
      oral administration of VY (10 mg/kg) to 18-week-old SHR resulted in a prolonged
      reduction of systolic blood pressure (SBP) up to 9 h (SBP0h 198.0+/-3.6 mmHg;
      SBP9h 154.6+/-3.5 mmHg). As a result of VY determination, a roughly 10-fold
      higher increment of plasma VY level was observed at 1 h than that at 0 h, whereas
      thereafter the level declined rapidly. In tissues, VY was widely accumulated in
      the kidney, lung, heart, mesenteric artery and abdominal aorta with the area
      under the curve over 9 h of more than 40 pmol h/g tissue; of these a higher VY
      level was observed in the kidney and lung. In addition, a mean resident time
      (MRT) for each tissue (>5 h except for liver) revealed that VY preferably
      accumulated in the tissues rather than in the plasma (MRT 3.8 h). Significant
      reductions of tissue angiotensin I-converting enzyme activity and angiotensin II
      level were found in the abdominal aorta as well as in the kidney, suggesting that
      these organs could be a target site associated with the antihypertensive action
      of VY.

PMID- 15473263
TI  - beta-hairpin folding and stability: molecular dynamics simulations of designed
      peptides in aqueous solution.
AB  - The structural properties of a 10-residue and a 15-residue peptide in aqueous
      solution were investigated by molecular dynamics simulation. The two designed
      peptides, SYINSDGTWT and SESYINSDGTWTVTE, had been studied previously by NMR at
      278 K and the resulting model structures were classified as 3:5 beta-hairpins
      with a type I + G1 beta-bulge turn. In simulations at 278 K, starting from the
      NMR model structure, the 3:5 beta-hairpin conformers proved to be stable over the
      time period evaluated (30 ns). Starting from an extended conformation,
      simulations of the decapeptide at 278 K, 323 K and 353 K were also performed to
      study folding. Over the relatively short time scales explored (30 ns at 278 K and
      323 K, 56 ns at 353 K), folding to the 3:5 beta-hairpin could only be observed at
      353 K. At this temperature, the collapse to beta-hairpin-like conformations is
      very fast. The conformational space accessible to the peptide is entirely
      dominated by loop structures with different degrees of beta-hairpin character.
      The transitions between different types of ordered loops and beta-hairpins occur
      through two unstructured loop conformations stabilized by a single side-chain
      interaction between Tyr2 and Trp9, which facilitates the changes of the hydrogen
      bond register. In agreement with previous experimental results, beta-hairpin
      formation is initially driven by the bending propensity of the turn segment.
      Nevertheless, the fine organization of the turn region appears to be a late event
      in the folding process.

PMID- 15473264
TI  - A 4.2 kDa synthetic peptide as a potential probe to evaluate the antibacterial
      activity of coumarin drugs.
AB  - The coumarin antibiotics are potent inhibitors of DNA replication whose target is
      the enzyme DNA gyrase, an ATP-dependent bacterial type II topoisomerase. The
      coumarin drugs inhibit gyrase action by competitive binding to the ATP-binding
      site of DNA gyrase B protein. The production of new biologically active products
      has stimulated additional studies on coumarin-gyrase interactions. In this
      regard, a 4.2 kDa peptide mimic of DNA gyrase B protein from Escherichia coli has
      been designed and synthesized. The peptide sequence includes the natural fragment
      131-146 (coumarin resistance-determining region) and a segment containing the
      gyrase-DNA interaction region (positions 753-770). The peptide mimic binds to
      novobiocin (Ka = 1.4+/-0.3 x 10(5) M(-1)), plasmid (Ka = 1.6+/-0.5 x 10(6) M(-1))
      and ATP (Ka = 1.9+/-50.4 x 10(3) M(-1)), results previously found with the intact
      B protein. On the other hand, the binding to novobiocin was reduced when a
      mutation of Arg-136 to Leu-136 was introduced, a change previously found in the
      DNA gyrase B protein from several coumarin-resistant clinical isolates of
      Escherichia coli In contrast, the binding to plasmid and to ATP was not altered.
      These results suggest that synthetic peptides designed in a similar way to that
      described here could be used as mimics of DNA gyrase in studies which seek a
      better understanding of the ATP, as well as coumarin, binding to the gyrase and
      also the mechanism of action of this class of antibacterial drugs.

PMID- 15473265
TI  - [D-Ala2]-Deltorphin I peptoid and retropeptoid analogues: synthesis, biological
      activity and conformational investigations.
AB  - The synthesis is described of a [D-Ala2]-deltorphin I peptoid analogue in which
      all amino acid residues have been substituted by the corresponding N-alkylglycine
      residues. The [D-Ala2]-deltorphin I retropeptoid was also prepared as well as
      [Ala1 ,D-Ala2]-deltorphin 1 and the corresponding peptoid. Structural
      investigations by FT-IR and fluorescence measurements were carried out on the
      synthetic analogues and on some [D-Ala2]-deltorphin 1 peptide-peptoid hybrids
      previously prepared. According to the fluorescence measurements the distance
      between the aromatic residues in the deltorphin I peptoid and retropeptoid is
      similar to that suggested for the delta- and micro-opioids, respectively.
      Measurements of CD in the presence of beta-cyclodextrin, and some preliminary
      pharmacological experiments were also performed. No dichroic bands are present in
      the spectrum of the [Ntyr1,D-Ala2]-deltorphin I, but an increasing dichroic
      effect appears in the spectra of both the deltorphin I peptoid and retropeptoid.
      Activity tests on isolated organ preparations showed that the modifications made
      produced a dramatic decrease in the agonistic activity of the synthetic
      derivatives.

PMID- 15473266
TI  - Research on double-probe, double- and triple-tip effects during atomic force
      microscopy scanning.
AB  - Information obtained by atomic force microscopy (AFM) depends strongly on the
      kind of probe or tip used; therefore, probe and tip effects have to be taken into
      account when verifying or interpreting the data acquired. In many papers, double
      tip effects have been mentioned while other research was done; however, there are
      only a few special reports on double- or triple-tip effects, especially double
      probe effects. In our paper, metaphase chromosomes of Chinese hamster ovary (CHO)
      cells, aggregates of pectin molecules, membrane surface of mouse embryonic stem
      cells, and R-phycoerythrin-conjugated immunoglobulin G complexes were imaged by
      AFM with high-quality probes, double-probe cantilever, and double-tip and triple
      tip probes, respectively, in order to determine double-probe, double-tip, and
      triple-tip effects during AFM scanning. We found that the double-probe, double
      tip, and triple-tip effects share the same principle, and that these effects
      correlate with distance and height differences between probes of double-probe
      cantilever or tips of double-tip or multiple-tip probes. Since many other factors
      influence double-probe or double-tip effects, more in-depth studies must be
      undertaken. However, this initial research will make all users of AFM techniques
      aware of double-probe and double-tip or triple-tip effects during AFM scanning
      and aid in verifying or interpreting the data acquired.

PMID- 15473267
TI  - Using the atomic force microscope to observe and study the ultrastructure of the
      living BIU-87 cells of the human bladder cancer.
AB  - In this study, the ultrastructure of living BIU-87 cells of human bladder cancer
      was mapped using atomic force microscopy to reveal the dynamic change of single
      cancerous cell division. Simultaneously, the feasibility and functional
      reliability of the atomic force microscope (AFM) were established and a
      laboratory model using AFM to study living cancerous cells was created. In this
      experiment, BIU-87 cells of human bladder cancer were cultured by conventional
      methods and grown in gelatin-treated dishes. A thermostat was used for preserving
      the cell's living temperature. Scanning of these cells using AFM was carried out
      in physiologic condition. The AFM images of the ultrastructure of living BIU-87
      cells as well as those of the cell's membrane and cytoskeleton were very clear.
      The dynamic phenomenon of single cell division was observed. It was concluded
      that the AFM was able to observe and depict the ultrastructure of living cells of
      human bladder cancer directly and in real time. This experimental model is
      expected to play an important role in elucidating the cancerous mechanism of
      bladder normal cells at the atomic or nanometer level.

PMID- 15473268
TI  - Accuracy and precision of quantitative energy-dispersive x-ray spectrometry in
      the environmental scanning electron microscope.
AB  - The accuracy and precision of quantitative energy-dispersive x-ray spectrometry
      in the environmental scanning electron microscope have been estimated using a
      series of copper / gold alloys of known composition. The mean values (five to six
      replicate experiments) had relative errors within +/- 5%, and most were within +/
      3.5%. All relative standard deviations were < 5% and most were < 3%. Since the
      standard specimens were large (approximately 500 microm) in diameter, electron
      scattering in the 2 torr of water vapor above the specimen did not affect the
      results. This level of accuracy and precision was possible only by using a novel
      specimen surface charge neutralization scheme.

PMID- 15473269
TI  - A balanced technique for preparation of specimens from pathogenicity studies for
      scanning electron microscopy.
AB  - This paper reports our experiences with preparing delicate biological specimens
      for scanning electron microscopy. Three different washing methods were evaluated:
      One method allowed the analysis of the location of the bacterium Mycoplasma
      mobile on piscine gill epithelium and the optimal evaluation of histopathologic
      changes caused by this microbe. These results were achieved when specimens were
      washed three times in a cacodylic acid buffer after completion of the in vitro
      infection experiment in gill explant cultures. We also found that of three
      different concentrations of glutaraldehyde, a fixation with a 1.5% solution was
      sufficient to achieve excellent structural preservation, even without using post
      fixation in osmium tetroxide. Furthermore, this study showed that the use of
      acetone-carbon dioxide in the critical point drying procedure resulted in well
      preserved piscine gill epithelium and mycoplasmas. Finally, long-term storage of
      tissue specimens in 0.1 M cacodylic acid buffer is possible if the buffer is
      changed on a monthly basis to avoid growth of unwanted microorganisms, such as
      fungi.

PMID- 15473270
TI  - Charging in scanning electron microscopy "from inside and outside".
AB  - This paper is an attempt to analyse most of the complicated mechanisms involved
      in charging and discharging of insulators investigated by scanning electron
      microscopy (SEM). Fundamental concepts on the secondary electron emission (SEE)
      yield from insulators combined with electrostatics arguments permit to
      reconsider, first, the widespread opinion following which charging is minimised
      when the incident beam energy E0 is chosen to be equal to the critical energy
      E(o)2, where the nominal total yield delta(o) + eta(o) = 1. For bare insulators
      submitted to a defocused irradiation, it is suggested here that the critical
      energy under permanent irradiation EC2 corresponds to a range of primary
      electrons, R, and nearly equals the maximum escape depth of the secondary
      electrons, r. This suggestion is supported by a comparison between published data
      of the SEE yield delta(o) of insulators (short pulse experiments) and
      experimental results obtained from a permanent irradiation for EC2. New SEE
      effects are also predicted at the early beginning of irradiation when finely
      focused probes are used. Practical considerations are also developed, with
      specific attention given to the role of a contamination layer where a negative
      charging may occur at any beam energy. The role of the various time constants
      involved in charging and discharging is also investigated, with special attention
      given to the dielectric time constant, which explains the dose rate-dependent
      effects on the effective landing energy in the steady state. Numerical
      applications permit to give orders of magnitude of various effects, and several
      other practical consequences are deduced and illustrated. Some new mechanisms for
      the contrast reversal during irradiation or with the change of the primary
      electron (PE) energy are also suggested.

PMID- 15473271
TI  - Medical disorders in pregnancy--who should see the women?

PMID- 15473272
TI  - Assessment of the usefulness of hemibody irradiation in painful bone metastasis.
AB  - Bone pain due to skeletal metastasis causes significant morbidity among cancer
      patients. A single large hemibody radiation field is shown to be effective in
      alleviation of pain for patients with wide-spread bone metastasis. Fifty
      documented cases of disseminated bone metastasis due to malignancy were evaluated
      to assess the efficacy of hemibody irradiation for pain control. Intensity of the
      pain was scored according to the 10th visual analogue score. The upper and/or
      lower segment of the body was exposed to a radiation dose of 6 Gy and 8 Gy
      respectively in single fraction applying extended SSD-technique, using a
      telecobalt unit. The sample consisted of 23 male and 27 female patients with a
      median age of 48 years. The primary malignancy was distributed as breast,
      myeloma, prostate, lymphoma and miscellaneous tumours. Thirteen patients were
      offered upper hemibody irradiation, 21 cases lower hemibody, and 16 patients were
      offered sequential double hemibody irradiation. The mean radiation field size was
      2000 cm2. Thirty per cent of the patients achieved complete and 70% achieved good
      partial pain relief within 24 to 36 hours post-treatment and the relief was
      maintained for 2 to 3 months. The benefit of hemibody irradiation in disseminated
      bone metastasis with pain is described.

PMID- 15473273
TI  - Clinical profile and outcome of stroke in relation to glycaemic status of
      patients.
AB  - The present study was undertaken in 50 patients of acute stroke to assess the
      role of glycaemic status on clinical profile and outcome of stroke. Subjects were
      divided into two groups: Group 1--Comprising of 25 patients of acute ischaemic
      stroke; Group 2--Comprising of 25 patients of acute haemorrhagic stroke. Each
      group was subdivided into euglycaemics, stress hyperglycaemics, newly diagnosed
      diabetics and known diabetics subgroups (stress hyperglycaemics, newly diagnosed
      diabetics and known diabetics together were called hyperglycaemics).
      Hyperglycaemics of both the groups had larger sized stroke. Neurological
      assessment done at day 1 and day 10 by Gillory's scoring system showed
      statistically significant improvement (P < 0.01) in all neurological functions in
      the euglycaemic subgroup in both the groups while in the hyperglycaemic subgroup
      improvement in higher mental function and motor function was insignificant (P >
      0.05). There was statistically significant mortality (P < 0.05) (up to 10th day)
      with the hyperglycaemic subgroup in both the groups as compared to the
      euglycaemic subgroup.

PMID- 15473274
TI  - Spectrum of renal disease in malaria.
AB  - Between January 2000 and December 2001, renal involvement in 81 cases of malaria
      was studied. Their age ranged between 05 and 66 (mean 35.5) years. Distribution
      of malarial parasite was P falciparum (75), mixed infection (4) and P vivax (2).
      The evidence of clinical renal disease in the form of acute renal failure,
      electrolyte abnormality, abnormal urinary sediment and increased urinary protein
      excretion (>500 mg/24 hours) was found in 100%, 91.3%, 46.9% and 18.5%
      respectively. Probable aetiopathogenesis of acute renal failure (ARF) was
      multifactorial. Volume depletion (72.8%) was the dominant cause of ARF in these
      patients. In addition, hyperbilirubinaemia, intravascular haemolysis and sepsis
      were responsible for ARF in 64.2%, 70.3% and 25.9% cases respectively. All the
      patients were managed with anti-malarial drugs and dialysis support was needed in
      35 patients (43.2%). Prognosis of malarial acute renal failure is favourable with
      mortality rate of 18.5%. Multi-organ failure was the commonest cause (33.3%) of
      death.

PMID- 15473275
TI  - Bronchoscopy in adults at a tertiary care centre: indications and complications.
AB  - Fibreoptic bronchoscopy (FOB) helps in visualisation of the endobronchial tree.
      Fibreoptic bronchoscopies were done in 429 cases between January 1999 and January
      2000 [322 men (75.1%) and 107 women (24.9%)]. Patients were between 12 and 89
      years of age (mean+/- SD = 49 +/- 15.1 years). Of which, 196 (45.7%) had lung
      cancer and 233 (54.4%) had non-malignant disease [Tuberculosis (TB) 26, miliary
      TB 16, non-resolving pneumonia 29, atypical pneumonia 10, bronchiectasis 11,
      aspergillosis 12, sarcoidosis 17, interstitial lung disease (ILD) 20, haemoptysis
      with normal chest x-ray 13 and miscellaneous 79]. In this series of 429 patients
      a significant number of patients (n = 127) presented with fever (38 malignant and
      89 non-malignant disease, p < 0.0001), 137 had haemoptysis (74 malignant and 63
      non-malignant disease, p < 0.01), 89 had chest pain (61 malignant and 28 non
      malignant disease, p < 0.0001) and 29 patients presented with complaint of
      anorexia (21 malignant and 8 non-malignant disease, p < 0.003). High prevalence
      of lung lesions in the right upper lobe [10.4% (43 of 411)] and left main
      bronchus [12% (49 of 411)] was observed. Left upper lobe showed 8.7% (36
      patients) lesions and right middle lobe showed 5.5% (23 patients) lesions. In 143
      (34.8%) patients, FOB findings were normal. Out of 407 patients, FOB was
      suggestive of necrotic/nodular growth in 159 patients (39.1%), infiltrative
      growth in 8 patients (1.9%), and extrinsic compression was found in 39 patients
      (9.6%). In 143 patients (35.2%) no endobronchial growth was seen. Bronchial
      biopsy (BB) was performed in 162 (37.8%) patients, transbronchial lung biopsy in
      56 patients (13.1%), bronchial washing for cytology in 350 patients (81.5%),
      bronchial washing for AFB in 302 patients (70.3%), bronchial washing for culture
      in 67 patients (15.6%), bronchial washing for fungus in 64 patients (14.9%) and
      Pneumocystis carinii infection was looked for in 6 patients (1.4%).
      Postbronchoscopy complications were recorded as follows: Early termination of FOB
      due to decreased O2 saturation in 10 cases (2.4%), postbiopsy bleeding in 5 cases
      (1.2%), post FOB fever in 5 cases (1.2%), chest pain in 7 patients (1.7%) and
      pneumothorax occurred in 2 patients (0.5%). FOB performed in outpatient setting
      is a useful and safe modality. Most patients in whom FOB was done in the present
      setup had suspected lung cancer. No major complications were encountered.

PMID- 15473276
TI  - The effect of alcohol on incidence, pattern, severity and outcome from traumatic
      brain injury.
AB  - Alcohol consumption is known to be a major contributing factor for the occurrence
      of traumatic brain injuries (TBIs) in both developed and developing countries. It
      also influences diagnosis, management and recovery from TBIs, subsequent to
      injury occurrence. The present report examines the association of alcohol in
      injury occurrence, and its impact on severity and outcome from TBIs. Subjects
      were identified from 7 major hospitals in the city of Bangalore, India with data
      collection undertaken by standardised methods. Alcohol users (n = 243) and non
      users (n = 1310) were compared on various characteristics and injury details.
      Sixteen per cent of the injured patients were intoxicated at the time of hospital
      registration. While the incidence of road traffic injuries was similar in both
      the groups, falls were higher in the alcohol user group. Evening-and night-time
      consumption of alcohol was a major risk factor for injuries. Drivers and
      occupants of motorised two wheeler vehicles, and pedestrians were involved in
      crashes to a greater extent among alcohol users. Severity of brain injuries
      (based on Glasgow coma scale), duration of hospital stay, death and post
      traumatic disabilities among alcohol users were significantly higher compared
      with non-users. With the emergence of injuries and alcohol as twin major public
      health problems, immediate efforts are required to reduce the burden in
      developing societies. Legislative and enforcement strategies along with education
      developed on epidemiological, clinical and public health research need to be co
      ordinated, target oriented, visible and with stiffer penalties for achieving
      desired results.

PMID- 15473277
TI  - Ovarian teratomas in Mangalore.
AB  - In the present study 122 ovarian teratomas, reported from the department of
      pathology, Kasturba Medical College, Mangalore, were predominantly (76%) seen in
      the age group below 40 years and the peak incidence was in the third decade
      (39%). Menstrual disturbances, pain abdomen, pregnancy and abdominal distension
      were the presenting symptoms. Histologically 113 (92.6%) were benign cystic
      teratomas showing mainly ectodermal tissue derivatives. Struma ovarii (4 cases)
      revealed colloid, both macro- and microscopically. Immature teratomas (2 cases)
      were solid and showed embroynal tissue elements. Teratomas with malignant
      transformations (3 cases) were grossly nodular and were squamous cell carcinomas.

PMID- 15473278
TI  - Management of spinal tuberculosis--current concepts.
AB  - Evidences of spinal tuberculosis have been found in Egyptian mummies and the
      disease is one of the oldest diseases afflicting humans. The demography,
      diagnosis, medical and surgical treatment, as advocated currently, have been
      reviewed with a brief discussion of the literature. Early diagnosis and
      comprehensive treatment are needed to control this public health problem.

PMID- 15473279
TI  - Wandering ascaris coming out through the T-tube tract--a rare occurrence.
AB  - A case of ascariasis of the common bile duct in the postoperative period of
      cholecystectomy and choledocholithotomy with T-tube drainage is reported. The
      living adult wandering ascaris came out through the T-tube tract immediately
      after removal of the T-tube. No such previous report has been found in the
      available literature.

PMID- 15473280
TI  - Boutonneuse fever in a child: a case report and overview.
AB  - A five and half year-old boy presented with an acute febrile illness associated
      with abdominal pain, generalised myalgia, arthralgia and skin rash. An elder
      sibling had a similar illness and had expired three days back. Initially
      crystalline penicillin and chloramphenicol were started. Investigations to
      diagnose the cause of fever viz, peripheral blood smear for malarial parasite,
      blood and urine cultures, Widal test and dot-ELISA for leptospirosis were
      negative. Weil-Felix test revealed a positive OX-2 titre of 1:100.
      Retrospectively, a history of close contact with dogs was elicited and a tick
      bite mark on the hand detected. Within five days of antibiotic therapy the fever
      resolved. Chloramphenicol was given totally for two weeks and the child recovered
      fully. Rickettsial infection should be considered in a child presenting with an
      acute febrile illness with skin rash since the response to specific antimicrobial
      therapy is dramatic and life saving.

PMID- 15473281
TI  - Guillain-Barre syndrome as a complication of enteric fever.
AB  - The incidence of neurological manifestations in enteric fever varies widely but
      the predilection of typhoid toxins to nervous system is well known. A case of
      enteric fever in a 10-year-old girl, who developed Guillain-Barre syndrome
      subsequently as a complication, is reported below with a brief review of the
      literature.

PMID- 15473282
TI  - Sialidosis type I (cherry red spot-myoclonus syndrome).
AB  - Sialidosis type 1 or the cherry red spot-myoclonus syndrome (CRSM) is an
      autosomal recessive disorder with the onset in adolescence of myoclonus and
      gradual visual failure. Here, a case of CRSM in a 12-year-old Bengali Muslim girl
      with the history of myoclonic jerks of limbs and the body since last 2 years and
      gradual impairment of vision since last one year is presented with a brief review
      of the literature.

PMID- 15473283
TI  - JIMA 2004, vol 102, no 01.

PMID- 15473284
TI  - Hydatid cyst of spleen in children.

PMID- 15473285
TI  - Blockage while giving intramuscular and subcutaneous injections.

PMID- 15473286
TI  - Road traffic accident--the present scenario and how to prevent it.

PMID- 15473287
TI  - Transcranial Doppler sonography evaluation in patients with vasospasm following
      subarachnoid haemorrhage.
AB  - Transcranial Doppler (TCD) sonography is emerging as a new ultrasonography
      technology to look at the interaction between the brain parenchyma and perfusion
      during cerebrovascular accident. Before TCD sonography the vasospasm following
      subarachnoid haemorrhage could only be diagnosed either clinically or by invasive
      method ie, angiography. TCD has been proved as a wonderful non-invasive,
      repeatable, beat-by-beat, non-expensive technique for detection and follow-up of
      vasospasm after subarachnoid haemorrhage. In the present series 12 patients
      suspected to have vasospasm after subarachnoid haemorrhage were confirmed and
      monitored with the help of TCD. Most of the patients were clinically presented
      with increasing headache and altered sensorium. It is noticed that vasospasm
      following subarachnoid haemorrhage has a typical course, which has increasing
      trend after 4th day of subarachnoid haemorrhage and declining trend after 14th
      day onwards. Six out of 12 patients were in moderate grade of vasospasm, 2 out of
      12 were in severe grade and 4 out of 12 were mild grade of severity.

PMID- 15473288
TI  - A study on morbidity pattern of child labourers engaged in different occupations
      in a slum area of Calcutta.
AB  - A cross-sectional study of 150 child labourers engaged in different occupations
      in a slum area of Calcutta was conducted to assess their health and nutritional
      status. Most (88%) of them had some type of morbidity. Female child workers
      (95.5%) suffered more than the males (84.7%). Most prevalent morbidities among
      the child labourers were seen as pallor (49.3%) followed by pediculosis (48%),
      dental caries (28.6%), malnutrition (22.6%), worm infestation (20.6%) and scabies
      (16.6%). Garage workers were observed to suffer less from any type of morbidity
      except pallor which may be attributed to lead exposure. Rag-pickers had
      significantly (p < 0.05) more risk of developing worm infestation, scabies and
      pediculosis whereas domestic helpers had significantly (p < 0.05) more risk of
      developing pediculosis. Occupational hazards were also studied but excepting
      pallor in garage workers and scabies in rag-pickers, nothing could be documented.

PMID- 15473289
TI  - The role of bed rest in acute low back pain.
AB  - Acute low back pain is a common problem and clinicians from a number of different
      disciplines are involved in its management. Advice on daily activities
      constitutes an important part in the management of low back pain. In spite of
      evidence against its efficacy, bed rest continues to be a cornerstone of
      treatment. The purpose of this review is to present evidence from literature to
      determine the effectiveness of bed rest for patients with acute low back pain
      together with comparison of bed rest versus advice to stay active, bed rest
      versus other treatment modalities and shorter periods of bed rest (2 to 4 days)
      versus longer periods (more than 4 days) of bed rest. There is strong evidence to
      suggest that bed rest is not effective in the management of acute low back pain.

PMID- 15473290
TI  - Acute management of atrial fibrillation: the commonest arrhythmia in clinical
      practice.
AB  - Atrial fibrillation is the commonest arrhythmia encountered in clinical practice.
      Whereas in western countries it is the elderly population who are at risk,
      however in countries like India, where rheumatic heart disease is rampant it is
      common cause of mortality and morbidity in the young. It is thus important that
      treatment of this disorder be disseminated to the level of the primary care
      giver. This would not only be beneficial to the patients who shall be getting the
      appropriate care dose at hand, but also reduce the burden of tertiary care
      centres who deal with more complex arrhythmias.

PMID- 15473291
TI  - Congenital epulis-a case report.
AB  - A full term newborn baby presented at the age of 2 days with a pedunculated mass
      arising from the mandibular gingiva and having difficulty in feeding. The mass
      was excised under general anaesthesia. Histopathology proved it to be a case of
      congenital epulis. The baby is doing well during follow-up one year after
      surgery.

PMID- 15473293
TI  - Can gradation of hospitals help patients?

PMID- 15473292
TI  - Anaphylactic reaction due to paracetamol.
AB  - A 58-year old woman had anaphylactic reaction two hours after oral administration
      of paracetamol. She was treated conservatively and responded favourably. This
      incident is being reported as anaphylaxis to paracetamol which is rare. Whenever
      there is history of allergy to other non-narcotic analgesic drugs, paracetamol
      sensitivity should be tested under medical supervision.

PMID- 15473294
TI  - Selective COX-2 inhibitors should be used judiciously in the presence of renal
      impairment.

PMID- 15473295
TI  - Ferric hydroxide polymaltose complex--an effective haematinic.

PMID- 15473297
TI  - IMA's policy statement on off-label usage.

PMID- 15473298
TI  - [Association of homozygous deletion of p15 and p16 gene and amplification of EGFR
      gene in laryngeal squamous cell carcinoma].
AB  - To assess the relationship of deletion of p15 and p16 gene and EGFR gene
      amplification in laryngeal squamous cell carcinoma (LSCC). DNA was extracted from
      fresh tumor. Deletion of p15 exon 2(p15E2) and p16 exon 2(p16E2) in 30 cases of
      LSCC was detected by polymerase chain reaction (PCR) technique. Amplification of
      EGFR gene in 30 cases of LSCC was detected by FISH. The rate of p15E2 deletion in
      30 cases was 13.3(4/30), and that of p16E2 was 16.7% (5/30). p15E2 and p16E2
      codeletion rate was 6.7% (2/30). The rate of EGFR gene amplification in 30 cases
      was 30% (9/30), and was amplified 2 to 8 fold. Homozygous deletion of p16E2 and
      p15E2 and codeletion is related with amplification of EGFR gene (P = 0.000018),
      and may play an important role to oncogenesis and malignant progression in LSCC.

PMID- 15473300
TI  - [A novel oligonucleotide arrays-based multiplex amplifiable probe hybridization
      technology].
AB  - Multiplex amplifiable probe hybridization (MAPH) has recently been developed to
      detect gene copy number changes in total genome in several genetic disease. Here
      we reported a novel oligonucleotide arrays-based multiplex amplifiable probe
      hybridization technology for DNA fragment copy number measurement. A set of
      amplifiable probes were prepared by locus-specific forward and reverse primers
      synthesized with the T7 and T3 promoter sites at their respective 5'-ends to the
      interest DNA fragments and purified by Qiagen PCR products purification kit. The
      set of probes were then hybridized with genome DNA immobilized on the nylon
      membrane. The selective probes after MAPH were collected with streptavidin coated
      magnetic beads and amplified by a biotin labeled universal primers. The
      biotinylated PCR products were then intended for hybridization to the
      corresponding oligonucleotide arrays consisted of 10 exons of DMD gene probes and
      positive,negative control probes immobilized on glass slides. After
      hybridization, the slides were washed by hybridization buffer and stained by
      streptavidin-Cy3. The hybridization fluorescence images were scanned by the
      ScanArray software and further quantitatively analyzed by the ImageJ software.
      Here we used oligonucleotide array technology to replace the agarose gel analysis
      for detecting the biotinylated PCR products so that extendable ability of
      parallel assay in our method had greatly been improved. One control female, one
      control male and one DMD patient were tested in this study. The results
      demonstrate the feasibility of high-throughput detection and relative
      quantification of DNA fragment copy numbers changes in total genome DNA
      combination of MAPH and high-density oligonucleotide arrays in single reaction.

PMID- 15473299
TI  - [Characterization of genomic structure and mutation analysis of SMARCA1 gene in a
      Smith-Fineman-Myers syndrome family].
AB  - The study is to determine the genomic structure and the role of SMARCA1 (SWI/SNF
      related, matrix-associated, actin-dependent regulator of chromatin, subfamily A,
      member1, SMARCA1) in the etiology of Smith-Fineman-Myers syndrome (SFMS). By
      comparing the cDNA sequence of SMARCA1 with the genomic sequences, genomic
      structure of SMARCA1 was determined, and conformed by amplifying and sequencing
      the sequences of exons and splicing junction. The results show that the genomic
      sequence of SMARCA1 gene exceeds 71.7 kb in length, and contains 24 exons and 23
      introns. All the exon/intron boundaries follow the GT-AG rule and are in good
      agreement with the exon/intron consensus sequence. The characterization of
      genomic structure of SMARCA1 gene allows us to detect disease-causing mutation
      within the gene and further study its biological function. The open reading frame
      of SMARCA1 was detected for mutation by PCR amplification and direct sequencing
      in affected males from SFMS family in Shandong China. The disease in SFMS family
      from Shandong is not caused by the mutation within open reading frame of SMARCA1
      gene.

PMID- 15473301
TI  - [Analysis of synaptonemal complex from a carrier with 46,XY,t(11;18) balanced
      translocation].
AB  - Over ten years ago, two male patients of pregnancy wastage, who were the carriers
      of 4;6 and 4;13 reciprocal translocations, respectively, were analyzed with
      synaptonemal complexes (SCs) by de Perdigo et al. They suggested that the
      pregnancy wastage should be caused by heterosynapsis, which reciprocal
      translocations resulted in. The heterosynapsis might avoid spermatogenesis
      failure, but easily induced non-disjunction of some chromosomes and led to
      occurrence of unbalanced gametes. A new male patient of the pregnancy wastage was
      detected in China three years ago. Karyotyping of the patient showed 11;18
      reciprocal translocation. Analysis of synaptonemal complexes (SCs) of the patient
      was performed using the EM technology of SC surface spreading, SDS treatment,
      AgNO3 staining. The SCs of 30 spermatocytes at pachytenes were analyzed. The SCs
      in electron micrographs were measured by the method published by de Perdigo et
      al. (1991). The results showed that each of the observed spermatocytes displayed
      20 autosomal bivalents, a quadrivalent 11;18 and a sexual bivalent. Of the 30
      spermatocytes, 21 each exhibited a quadrivalent of adequate quality for
      measurement and interpretation. The 21 quadrivalents were classified into three
      types: type I, quadrivalents with fully paired arms with the expected cross
      configuration, two quadrivalents were of this type. Type II, quadrivalents with
      an evident heterosynapsis, forming five SC segments (four fully pairing arms and
      one middle pairing region), six quadrivalents were of this type. Type III,
      quadrivalents with four paired arms, but with asynapsed regions around the
      breakpoints, thirteen quadrivalents were of this type. Based on configuration,
      quadrivalents were classified into cis-configuration with above three types and
      trans-configuration with above two types except type I. Each of the analyzed
      quadrivalents showed four synaptic arms, which respectively paired between
      chromosome 11 and t18 (the translocated 18;11), 18 and t18, 18 and t11 (the
      translocated 11;18), and 11 and t11, and the arms were designated as A, B, C, and
      D correspondingly. The measurements of A and D as well as B and C observed in
      different cells were taken by calculating the percentages of their lengths in
      comparison to the length of chromosome 11 and 18, respectively. So were the
      middle synaptic regions. Measurements of SCs revealed that the location of the
      putative breakpoints estimated from the fully paired quadrivalents were different
      from those determined by G-band analysis for mitotic chromosomes. The length of
      the paired and unpaired segments varied from one quadrivalent to another. For
      instance, in the case of fully paired A and D arms, the breakpoint was located
      near to 45.59% and 38.53% of the length of the normal chromosome 11, the
      breakpoint from the mitotic chromosome was estimated to be near to 45%. The
      location of the putative breakpoints estimated from the No. 1 quadrivalent was
      consistent with the breakpoint from the mitotic chromosome. This suggested that
      only this quadrivalent showed complete homologous pairing. Obviously, the lengths
      of middle pairing region in type II quadrivalent were different from one
      quadrivalent to another. The middle pairing region/the length of the normal
      chromosome 11 is 4.11% - 18%, that/the length of the normal chromosome 18 is 8% -
      41.1%. The middle pairing regions should be the heterologous pairing regions in
      quadrivalents. The quadrivalents with unsynaptic regions also showed partially
      heterologous synapsis. In 14 of 21 quadrivalents, the paired regions overlapped
      the mitotic breakpoint position in chromosome 11. In 20 of 21 quadrivalents, the
      paired regions overlapped the chromosome 18 of mitotic breakpoint position in one
      or two arms. As synapsis can proceed homologously only up to the breakpoints, a
      heterosynapsis apparently occurred in 20 quadrivalents. The length of the paired
      and unpaired segments varied from one quadrivalent to another, and the
      measurements of the arms of the quadrivalents could not be used to determine
      breakpoints. The unpaired segment showed a thick and sometimes a split aspect
      similar to that of the sexual bivalent. Of the 20 quadrivalents with
      heterosynapsis, four were at early pachytene stages, fourteen at the middle and
      two at the late, respectively. The heterosynapsis, which occurred on the early
      pachytene, was without previous homosynapsis. This was different from the
      classical "synaptic adjustment" during the late pachrtene of spermatocytes. Many
      researches on reciprocal translocation associated with pregnancy wastage have
      been reported. It is most possible that the wastage detected in this study was
      related to the t(11;18). Normal synapsis finishes at early pachytene, while in
      the observed proband, most of the quadrivalents still left unsynaptic parts
      during middle and late pachytene stages. Obviously, the synapsis was delayed or
      incomplete. The unsynaptic regions distributed mainly in the central regions. The
      central regions perhaps completed the synapsis more late, therefore they had more
      chances to leave the unsynaptic parts. In addition, the results of SC analysis
      showed that heterosynapsis occurred wildly and was exhibited from early to late
      pachytene stages. It has been reported that crossing over could be inhibited by
      heterosynapsis in mice, man and boar, and normal segregation needs existence of
      crossing over. Therefore, heterosynapsis may interfere in normal segregation.
      Both unsynapsis and heterosynapsis could induce incidence of unbalanced gametes.
      In general, the unbalanced gametes are lethal and could not take part in
      fertilization, once they fertilize with normal eggs, the risk of pregnancy
      wastage or other genetic disorders will exist certainly. Our results showed that
      the heterosynapsis occurred widely, so a poor risk of pregnancy wastages caused
      by reciprocal translocation probably is not unusual.

PMID- 15473302
TI  - [Mapping quantitative trait loci for meat quality trait in a Large White x
      Meishan cross].
AB  - To search for the chromosome regions for quantitative trait loci (QTL) affecting
      meat quality in pigs, a three-generation resource family was developed in China
      using three Large White grand sires and seven Meishan grand dams. A total of 147
      F2 progenies derived from two populations in 1998 (n = 81) and 2000 (n = 66) were
      phenotyped for meat quality. All animals were typed for 48 microsatellite markers
      covering six chromosomes: 1, 2, 3, 4, 6 and 7. Linear model and least square
      analyses were used for interval mapping meat quality in jointed population and
      single population, permutation for empirical threshold. The strongest linkage at
      chromosome-wide level (P < 0.01) and genome-wide level (P < 0.05) on chromosome 4
      affecting intramuscular fat (IMF) QTL from the population in 2000 was detected
      with explained phenotypic variance of 5.24%, and Meishan's QTL increased the
      intramuscular fat content. There was a suggestive QTL for IMF near the threshold
      of chromosome-wide in the same region in jointly population. The QTL for pH value
      in m. Semispinalis Capitis and m. Biceps Femoris were located on chromosomes 1
      and 3, respectively. One and three QTL affecting WHC reached the thresholds of
      chromosome-wide level in the populations of 1998 and 2000, respectively. In the
      population of 1998, QTL for moisture content at chromosome-wide level was on SSC6
      and in jointed populations were on SSC2, 6 and 7. There were imprinting effects
      in moisture content QTL, and Meishan and Large White pigs all had favorable
      effects influencing moisture on different chromosomes.

PMID- 15473303
TI  - Phylogenetic relationships of the cypriniformes tested by mtDNA 12S rRNA sequence
      variations.
AB  - Cypriniformes is the largest order of freshwater fishes. The phylogenetic
      relationships of the Cypriniformes have been studied by many investigators based
      on morphological characters, but no agreement has been reached. In the present
      paper, complete mitochondrial 12S rRNA sequences of five families of the
      Cypriniformes were determined and analyzed to test the present morphological
      hypotheses. After alignment, there are 1000 sites, among which 467 sites are in
      stems and 533 sites in loops. 395 sites are variable, and of which 267 are
      informative. Neighbor-joining and Maximum Parsimony methods were employed for
      phylogenetic analysis. The results indicate that the cyprinids form a
      monophyletic group while the non-cyprinid cypriniforms form another one, which is
      in accordance with the hypothesis proposed by Siebert. The Cyprinidae consists of
      three main clades, the Danionini, the Cyprinini, and the Leuciscini. However, in
      the non-cyprinid cypriniforms, the relationships could not be resolved clearly.
      The Cobitidae is polyphyletic. Homalopteridae, Noemacheilinae and Cobitinae may
      have closer relationships.

PMID- 15473304
TI  - [SSR polymorphism of Alligator sinesis and conservation strategy of genetic
      diversity].
AB  - Chinese alligator, Alligator sinesis, is a critically endangered endemic species
      under legislative protection. Results of recent investigations revealed that the
      number of the alligator was continuously declining in the past 50 years and less
      than 150 individuals were surviving in the wild until 2000. In order to prevent
      the extinguishing of this species, the Reproductive Research Center of Alligator
      sinesis and the National Nature Reserve of Alligator sinesis were set up in early
      1980s in Xuanzhou, Anhui Province. After 20 years of breeding efforts, the number
      of captive individuals has been brought up to more than 10,000 in total. In order
      to reveal the genetic structure of Chinese alligator population, total of 39
      individuals including 7 wild individuals outside of the research center were
      sampled to construct wild, F1 and F2 groups according to their generations, and
      10 micorsatellite loci selected from 25 primer pairs originally designed for
      Alligator mississippiensis were employed for investigating the genetic diversity
      of Alligator sinesis. The results indicated that, contrasting with Alligator
      mississippiensis and some other endangered species, Chinese alligator had an
      extremely low genetic diversity level with A = 2.38, Ne = 1.60, Ho = 0.374, He =
      0.350 and PIC = 0.327. There were no significant differences of A, Ne, Ho, He,
      PIC and each SSR locus alleles frequency distribution among 3 groups. However,
      Hardy-Weinberg equilibrium analysis revealed that F2 captive group showed a
      remarkable genetic disequilibrium at loci Ami-mu-6 and Ami-mu-222. The reason
      accounting for the current genetic status of Chinese alligator is dramatically
      shrink of the population in past decades. Due to the lack of significant
      difference between wild group and captive group, all survived Chinese alligator
      should be treated as one ESU in the next conservation practice. More attention
      regarding the effective population size and low frequency alleles should be
      emphasized in genetic management of captive alligators and establishing new
      separate propagation.

PMID- 15473305
TI  - [Determination of transcription initiation site of chicken ovalbumin gene and
      construction of its expression vector].
AB  - To determine the core promoter of chicken ovalbumin gene and 5' upstream regions,
      the transcription initiation site of ovalbumin gene was confirmed by 5'RACE
      method, at the same time, the regulatory elements of chicken ovalbumin gene were
      determined by sequence analysis. To investigate the ability of regulatory
      elements to direct the exogenous gene expression, 1.5 kb fragment and 2.9 kb
      fragment were amplified by PCR method. Two fragments were subcloned to mammalian
      expression vector pGFP-N2 by recombinant DNA technology, the CMV promoter was cut
      off from pGFP-N2. Two expression vectors were constructed, one is the P2.9koval
      GFP including promoter,first exon,first intron of chicken ovalbumin gene, and the
      other is the P1.5koval-GFP including first intron of chicken ovalbumin gene.
      Restriction enzyme digestion and DNA sequence analysis revealed that 5' upstream
      regions of ovalbumin gene were not only identical to those of the published
      chicken ovalbumin gene, but also were contained in the recombinant vector.

PMID- 15473306
TI  - [Genetic relationships among five populations of Oxya chinensis in Shanxi
      Province and adjacent region based on RAPD].
AB  - Random Amplified Polymorphic DNA (RAPD) markers were applied to analyze genetic
      relationships of five populations of Oxya chinensis collected from Shanxi
      Province and laner Mongolia, Oxya japonica from Guangxi was used as an outgroup.
      Genomic DNA of sixty-four individuals was extracted from dissected leg muscle
      using phenol-chloroform procedure, and then amplified by 10 random primers (10
      bp), the amplified products were separated by agarose gel electrophoresis. The
      results were as follows: (1) a total of 115 clear and reproducible bands were
      generated, molecular size was 200 - 2500 bp. The obtaining segments of individual
      primer were among 5 - 15, on average, about 12 bands per primer. (2) The
      dendrogram based on 115 RAPD markers was constructed and clustered using between
      groups linkage method. The cluster analysis indicated strong similarities within
      populations, firstly, the individuals in each population closely clustered
      together;and then five populations of Oxya chinensis could be distinguished with
      RAPD markers and were grouped into two distinct clusters. The dendrogram showed
      that Shanxi Linyi population and Tunliu population were the most similar,which
      were clustered with Taiyuan population Shanxi into one cluster, while, Daixian
      population in Shanxi was closely related to laner Mongolia population, both of
      which belonged to the other cluster. Nevertheless, All the five populations of
      Oxya chinensis had far genetic distance with Oxya japonica. In the dendrogram, a
      tendency of clustering following a North-South gradient could be observed, the
      results implied that genetic distance of five populations of Oxya chinensis
      correlated with geographical distance to some degree.

PMID- 15473307
TI  - [Transcriptional differences between a heterokaryon and its segregants of
      Fusarium oxysporum f. sp. vasinfectum].
AB  - In order to elucidate the mechanism of fungal heterokayosis, a wild type strain
      of Fusarium oxysporum f. sp. vasinfectum was isolated from the cotton field in
      Anyang, Henan Province. Through single hyphal-tip isolation, a heterokaryon,
      Ag149, was obtained, and its two different phenotypic segregants, Ag149-I and
      Ag149-III, were separated from the mutated sectors on colony of the heterokaryon.
      They have remarkable differences on color of colony, morphology of hypha and
      pathogenicity. After analyzing by RAPD on their nuclear DNA with 100 random
      primers, no polymorphic difference was found among them. On going to find the
      different expressed gene, the mRNA differential display method was performed. Two
      kinds of reverse transcriptase AMV and MMLV, and a kit which consists of three
      kinds of 3' terminal anchor primers and eight kinds of 5' terminal arbitrary
      primers were used in differential display PCR (DD-PCR). Total RNA as template was
      reverse transcribed into corresponding cDNA by 3' terminal anchor primers, and
      the cDNA were amplified by polymerase chain reaction with a set of one same 3'
      anchor primer and one 5' arbitrary primer. The PCR products were then resolved on
      denaturing polyacylamimide gel, and the cDNA bands were visualized by silver
      staining. Among the 144 PCR products, 19 differentially expressed cDNA fragments
      ranged from 300 bp to 700 bp were purified. All of them were ligated to pGEM-T
      vector respectively for sequencing and Rev-Northern blotting. Two cDNA fragments
      (G5 and C6) were observed to be positive after Rev-Northern blotting. The C6 was
      highly expressed in the heterokaryon Ag149 and its segregant Ag149-I. It is 564
      bp in length and can be predicted 77 amino acids from the beginning of the 3rd to
      233th base, and then searched from GenBank. The amino acid sequence of C6 shared
      homologies with the 6th subunit of NADH dehydrogenase found in some bacteria,
      plants and animals at 30% - 70% level. While the G5 was highly expressed in Ag149
      and its segregant Ag149-III. It is 432 bp in length and can be predicted 101
      amino acids from the beginning of the 2nd to 304th base, and the amino acid
      sequence is 35% homologies comparing with the tetracycline efflux protein (OtrB)
      of Streptomyces rimosus. We also checked these two kinds of the pGEM-T vector
      harboring cDNA fragments (C6 and G5) by Southern blotting with their nuclear DNA
      and mitochondrial DNA (mtDNA) separately. The positive identification signals
      only appeared from nuclear DNA,and it addressed that C6 and G5 locate on their
      nuclear genome. The result indicated that the difference between the heterokaryon
      and its segregants is distinct on gene transcriptional level. Thus a molecular
      evidence for the formation of heterokaryon in filamentous fungi was provided.

PMID- 15473308
TI  - Cloning and expression analysis of carboxyl-terminal protease cDNA from Gossypium
      hirsutum L.
AB  - A full-length cotton cDNA,designated GhCtp, was isolated from Gossypium hirsutum
      L. by the PCR-based cDNA library screening. The cDNA encodes a polypeptide of 473
      amino acid residues. Sequence alignment showed that GhCtp was highly homologous
      to a family of carboxyl-terminal proteases (Ctp) from other species. GhCtp is a
      potential transmembrane protease, and comprises a conserved domain numbered
      DUF239 at its carboxyl-terminal and an arginine-rich region at the amino
      terminal, respectively. Furthermore, there is a putative ATP-/GTP-binding site
      motif A (P-loop) in GhCtp which do not exist in Ctps of Arabidopsis and Oryza,
      indicating that GhCtp might function in a manner different from other Ctps. RT
      PCR analysis suggested that GhCtp was not a fiber-specific or -preferential gene,
      and had a low expression level in different tissues or developmental stages of
      cotton.

PMID- 15473309
TI  - [A SC35-like protein is localized in the nucleus of Physarum polycephalum].
AB  - After being labeled with an anti-SC35 antibody, the specimens of Physarum
      polycephalum at S, G2, prophase, metaphase and ana-telophase were observed with
      an Hitachi electron microscope and gold particles marking the location of the
      SC35-like protein were mainly found in the nucleus,indicating the existence of a
      SC35-like protein in it. Judging from the densities of the gold particles in the
      individual domains of the nucleus, the SC35-like protein was principally located
      in the nucleolar domain and interchromatin domain during G2 and prophase, and the
      protein was distributed in the interchromosome domain at metaphase and ana
      telophase when the nucleus was disintegrated, suggesting that the nucleolus and
      interchromatin (interchromosome) domain are the two main locations of the SC35
      like protein in the nucleus. Further observations upon the nucleolus revealed
      that the density of the gold particles in the dense fibrillar component (DFC) of
      the nucleolus was much higher than that of the fibrillar center (FC),
      demonstrating that the protein was largely situated in the DFC rather than FC.

PMID- 15473310
TI  - [Transgenic cotton plants of chitinase and glucanase genes and their performance
      of resistance to Verticillium dahliea].
AB  - The two disease-resistance genes chitinase and glucanase, which were respectively
      directed by commelina yellow mottle virus promoter (CoYMV, vascular specific) and
      CaMV35S promoter, were introduced into cotton genome via Agrobacterium
      tumefaciens. Transgenic plants were obtained from two popularly cultivated
      varieties Jihe321 and CRIC35. After screening by spraying kanamycin over
      unfolding leaves, the kanamycin resistance (KmR) plants were tested by PCR and
      Southern blot. The results showed that there were one or two inserts of
      transgenes in cotton genome. Performance test of resistance of T3 families in
      field and greenhouse showed that seven lines were resistant or tolerant to
      Verticillium dahliea. Meanwhile, the resistance at seedling stage in greenhouse
      was in accordance with that at the boll-setting stage in field. Among the seven
      lines, D9910, D9915 and D9919 had a disease resistance index of 6.5, 9.4 and 9.5,
      respectively in field, which showed a high resistance level. Genetics analysis of
      the three lines showed a classical Mendelian pattern of one pair of genes, which
      meant that each of the three lines contains one copy of transgene. Southern
      blotting also confirmed the copy number of inserts.

PMID- 15473311
TI  - [Obtainment of transgenic wheat with the insecticidal lectin from snowdrop
      (Galanthus nivalis agglutinin; GNA) gene and analysis of resistance to aphid].
AB  - Snowdrop lectin (Galanthus nivalis agglutinin; GNA) is toxic to sap sucking
      injurious insects of Homopteran. A new gna gene has been transferred into common
      spring wheat Zhong60634 and winter wheat Yumai66 with high yield by using the
      biolistic transformation method. Transgenic wheat plants have been obtained in
      both of the two varieties. Two transgenic plants (T0) have been obtained from the
      bombarded 535 immature embryos of Zhong60634. Bioassay results show that the
      development of aphid could be slowed down and the survival rate of young aphid
      could be reduced by gna gene. Seventeen transgenic plants (T0) were obtained from
      the bombarded 4636 immature embryos of Yumai66. Twenty plantlets with good
      resistance to Rhopalosiphum padi and Macrosiphum avenae, which are mainly aphid
      in north wheat area, were identified from the transgenic plants of T1 generation
      that came from 8 T0 transgenic plants with good resistance to aphid. The anti
      aphid bioassay shows that resistance to the different grain aphid is not the same
      in transgenic wheat plants. To Rhopalosiphum padi, the rate of survival aphid 8
      days after exposing transgenic plants to aphids is significantly lower than that
      of nontransgenic plants. To Macrosiphum avenae, growth speed of aphids is slowed
      down but not killed. At the same time, the death rate of young aphids is
      increased. Anyway, feeding of the two kinds of aphids has been controlled in a
      certain degree by gna gene when aphids can free to move in plants.

PMID- 15473312
TI  - [Inheritance and expression of the maize pepc gene in progenies of transgenic
      rice bred by crossing].
AB  - By cross breeding, the maize pepc gene in the pepc transgenic rice was
      successfully incorporated into the parents of two-, three-line hybrid rice,
      including sterile lines (Peiai64S, 2302S, 2304S, 2306S and Shuangjiu A) and
      restorer lines (5129, 02428 and Wanjing97) to breed the high-photosynthetic
      efficiency parents of hybrid rice and utilize heterosis between C4 and C4/C3
      rice. Some lines of pepc transgenic rice (LPTR) have been developed. The study on
      the generations of LPTR suggests the following: (1) The segregation observed in
      F2 and BC1 progenies demonstrated that pepc transgene inherited as a single
      dominant gene in the progenies of LPTR. (2) The maize pepc gene is actively
      expressed at high level in LPTR, and changes of pepc gene expression in the
      progenies of LPTR may be related to position effect, difference of gene copy
      number and environmental factors. (3) Through the selection method of soaking
      seeds into hygromycin solution to germinate, tracing the pepc gene by PCR
      analysis, evaluating the performance of the rice plants in the field and
      examining PEPC activities, the segregation of the pepc transgene in LPTR was
      controlled effectively. Based on the above strategy three pepc transgene lines,
      H1596, H1597 and Y1470, have been selected. The result suggests that it is
      possible to breed practical, stable and high-expression pepc transgenic rice by
      conventional crossing.

PMID- 15473313
TI  - [Multiple nonlinear statistical method of population genetic structure based on
      the allelic polymorphism data].
AB  - The distribution and structure of the allelic polymorphism data are analyzed and
      it is pointed out that the distribution of allelic polymorphism data reveals the
      characteristic of closed data (also named as compositional data or data of
      constant sum). It is interpreted that the correlation structure of the allelic
      polymorphism data contains null correlations introduced by "closure" and the
      statistical distribution of the data is not normal because of its constant row
      sum, which resulted in great difficulties in analyzing the data with traditional
      multiple linear statistical methods such as principal component analysis, factor
      analysis, cluster analysis and canonical correlation analysis. Based on the
      theory of compositional data analysis proposed by Aitchison in 1982, a multiple
      nonlinear statistical method originating from the "logratios" approach to the
      statistical analysis of compositional data is put forward in this paper. As an
      example, the "logratios" method was used to analyze the genetic structure of TH01
      polymorphic loci in Chinese population and the results were compared with those
      of multiple linear methods such as component principal. It is concluded that the
      "logratios" multiple nonlinear principle component analysis is a better method
      with the virtue of sensitivity and specificity for analyzing the genetic
      structure of population from the data of allelic polymorphism.

PMID- 15473314
TI  - [ATM and telomere instability].
AB  - Accumulation of DNA damage has been associated with the onset of senescence and
      the predisposition to cancer. The gene responsible for ataxia telangiectasia (A
      T) is ATM (Ataxia-telangiectasia mutant), a master controller of cellular
      pathways and networks, orchestrating the response to a specific type of DNA
      damage, i.e., the double strand break. It has now been demonstrated that
      mutations in ATM lead to defective telomere maintenance in mammalian cells. This
      review will focus on its roles in telomere metabolism and how ATM and telomeres
      serve as controllers of cellular responses to DNA damage.

PMID- 15473315
TI  - Systematically experimental investigation on carcinogenesis or tumorigenicity of
      VERO cell lines of different karyotypes in nude mice in vivo used for viral
      vaccine manufacture.
AB  - Many cell lines used for vaccine production have a potentially strong tumorigenic
      character. Some of those routinely used need to be checked at different passage
      numbers for this characteristic. Using HeLa cell cultures as positive controls,
      and primary canine kidney cell (CKC) or feline kidney cell (FKC) cultures
      purified in vitro on passage three as negative controls, the tumorigenicity of
      VERO cell sublines was tested in 219 nude mice. The master cell stocks (MCS) and
      working cell banks (WCB) of eight strains of VERO African green monkey kidney
      cell (AGMKC) line used for canine, feline and mink vaccine preparation were
      established in China. The hypo-tetra-ploid JA or hyper-diploid KA strain of VERO
      line was highly tumorigenic. These data showed a variable chromosome karyotype of
      VERO line, and contraindicated the use of JA or KA strain of VERO line for the
      preparation of attenuated viral vaccines. JA or KA strain of VERO line could be a
      substitute for HeLa line as a positive-control malignant tumor (MT) cell model.
      The non-carcinogenic YB, JC, M and JB strains of VERO line were therefore
      selected for the preparation of modified live rabies viral vaccine in place of
      BHK-21. The cell sub-lines are comparatively stable in terms of their heritable
      characters, and show little significant changes between passages. In summary, we
      have found that: 1) the tumorigenicity of cell line is different among different
      karyotypic cells; 2) it is the genetic characteristics of chromosomes of cell
      lines that determines their tumorigenicity, but with species-specific
      carcinogenicity; 3) the chromosome number variation of cell lines has positive
      relationship with their carcinogenesis; 4) highly variable strains of tumor cell
      line can be selected quickly and successfully in nude mice by alternate
      cultivation in vitro and in vivo. Malignant rhabdoid tumor (MRT) was evolved in
      nude mice inoculated with violently variable HeLa or VERO cells. The importance
      of assessing the tumorigenicity in cell sublines used for vaccine production is
      emphasised.

PMID- 15473316
TI  - CDNA cloning of a short isoform of human liver NADP (H) -dependent retinol
      dehydrogenase/reductase and analysis of its characteristics.
AB  - In this report we found a new short PCR product when we amplified a 635 bp of
      NRDR fragment by RT-PCR. With 3'-Race and 5'-Race,we obtained two full-length
      cDNA sequences from human liver tissue,one 1 261 bp NRDR cDNA,another 1 003 bp
      NRDR isoform (NRDRiso,GenBank accession number:AY071856). The NRDR gene comprises
      eight exons and seven introns. The NRDRiso cDNA is produced by alternative
      splicing of NRDR cDNA, with the removal of 4, 5, 6 exons composed of consecutive
      258 bp. The open reading frames of the NRDRiso cDNA predict a single polypeptide
      of 174 amino acids with the calculated minimum molecular mass of 18.6 kDa.

PMID- 15473317
TI  - [The Elp4 subunit of human Elongator complex partially complements the growth
      defects of yeast ELP4 deletion strain].
AB  - In this study, we performed in vivo experiments to determine the function of
      human Elongator subunit Elp4 by using a yeast complementary system. Our results
      indicated that though human ELP4 was not able to complement the growth defects of
      the ELP4 deletion mutant strain to high concentration salt, it partially reduced
      the sensitivity of mutant strain to caffeine, high temperature and 6-AU. Gene
      expression analysis indicated that human ELP4 partially resumed the slow
      activation of the PHO5 gene caused by the deletion of yELP4 under the low
      phosphate concentration. Meanwhile, under the condition of heat shock treatment,
      hELP4 increased the expression level of SSA3 gene. All these data demonstrated
      that human ELP4 can partially complement the growth defects and restore the slow
      activation of certain genes of the yELP4 deletion strain. These results indicate
      that human Elp4 subunit has similar functions to that of the yeast.

PMID- 15473318
TI  - Expression, purification and bioactivity characterization of extracellular domain
      of murine osteoprotegerin ligand.
AB  - Osteoprotegerin ligand (OPGL) is a key regulator of formation and activation of
      osteoclasts. In the present study, the cDNA encoding the extracellular domain of
      murine OPGL (sOPGL) was synthesized by RT-PCR and cloned into fusion expression
      vector pET-42a(+) in a certain strategy on purpose that the fusion tag could be
      completely removed by factor Xa from the expressed fusion protein without any
      vector-encoded sequence left. Induced with IPTG, the recombinant E. Coli cells
      produced a 47 kD protein in high level that could be recognized, through Western
      blotting analysis, by the antibody against OPGL. The expressed products were
      purified through Glutathione-sepharose 4B affinity chromatography. Along with the
      fusion molecule, a protein about 30 kD was also specifically bound to the resin.
      The 30 kD molecule could be recognized by polyclonal antibody against GST-IGF-1,
      but not by antibody against OPGL. It suggested that the 30 kD molecule was
      derived from the degradation of the fusion protein. After the cleavage with
      factor Xa and further purification, the fusion tag was removed and the
      recombinant sOPGL was obtained. Finally, we confirmed that the recombinant sOPGL
      could promote osteoclast formation from mouse bone marrow cells in a dose
      dependent manner.

PMID- 15473319
TI  - [Characterization of tissue expression of peroxisome proliferator activated
      receptors in the chicken].
AB  - The peroxisome proliferator activated receptor (PPAR) is the member of super
      family of nuclear receptors. A great number of researches in rodent and human
      have showed that PPARs are involved in the lipids metabolism, especially in
      regulating the microsome,expression of genes coding the various enzymes during
      the beta-oxidation of peroxisome and the differentiation of adipose cell. The
      PPARs are one of the important gene clusters that are viewed as the objective
      genes correlated with the lipids metabolism and corresponding diseases. Great
      differences in lipids metabolism are existed between the poultry and mammals. The
      mechanism of the lipids metabolism in poultry is not completely understood. The
      current study was designed to investigate the expression characterization of PPAR
      genes in chicken in order to understand the effects of PPAR gene on adipose and
      other tissues. The eight weeks age Arber Acres broilers were used and
      quantitative RT-PCR and Northern blot were developed to analyze the expression
      characterization of PPAR-alpha and PPAR-gamma gene in heart, liver, spleen, lung,
      kidney, stomach, intestine, brain, muscle and adipose tissues. Results of the
      quantitative RT-PCR showed that the expression level of PPAR-alpha gene was
      higher in brain, lung, kidney, heart and intestine, medium in stomach, liver and
      adipose, and lower in spleen. But did no expression was detected in breast
      muscle. The expression level of PPAR-gamma gene was higher in adipose, medium in
      brain and kidney, lower in spleen, heart, lung, stomach and intestine, but no
      expression was detected in liver and breast muscle. Northern blot results showed
      that PPAR-alpha gene expressed in heart, liver, kidney and stomach, and the
      intensity of hybridization signal was the greatest in liver tissue; PPAR-gamma
      gene only expressed in adipose and kidney tissues, and the intensity of
      hybridization signal was greater in adipose tissue. The present study results
      showed that the tissue expression characterization of PPARs gene in chicken was
      almost consistent with that in rodent and human, but, in chicken, PPAR-alpha did
      not expressed in breast muscle and PPAR-gamma gene expressed in kidney. The
      results of current research indicated simultaneously that the PPAR genes were
      related with the growth and development of various tissues and organs.

PMID- 15473320
TI  - [Cloning and characterization of the promoter region of Musca domestica yolk
      protein-1 gene].
AB  - A partial Musca domestica genomic library was constructed. It was consisted of
      1.2 x 10(5) recombinants with insert length ranging from 10 kb to 23 kb(15 kb
      average). High molecular weight genomic DNA with more than 50 kb size was
      extracted from the larva hatched 36 h and digested with unfrequently cutting
      restriction enzyme Bcl I. DNA fragments of 10 approximately 23 kb were recovered
      by agarose gel electrophoresis and ligated with EMBL3 BamH I Arms CIPase treated.
      Then the products of ligation were packed in vitro using packing protein. The
      cloning efficiency of the genomic library was 5 x 10(4) pfu/mL. The genomic
      library was screened by hybridization using a probe of a 768 bp partial cDNA
      fragment of Musca domestica yolk protein 1 (mdYP1) gene obtained by PCR and the
      probe was labeled with Digoxigen. A positive plaque was chosed and purified by in
      situ hybridization. A genomic DNA fragment about 4.0 kb mdYP1 was isolated from
      purified positive plaque by southern blotting analysis. Sequence analysis
      revealed that mdYP1 genomic gene was composed of 5'-upstream region about 1.7 kb
      with typical CAAT/TATA box. The promoter of the mdYP1 gene was characterized by
      examining the ability of 5'-upstream fragments to regulate expression of green
      fluorescent protein (GFP) in Musca domestica larva. Four fragments of the
      promoter region, P1 (+296/+7), P2 (+684/+7), P3(+1165/+7) and P4 (+1616/+7) ,were
      obtained by PCR specific amplification using template of recombinant A-lambdaNA
      containing mdYP1 gene sequence. Then the four fragments were respectively
      subcloned into pCMV-GFP reporter vector deleted CMV promoter. All the fragments
      showed no promoter activity when the four recombinant vectors were transfected
      into Sf9 and BHK -2 cells respectively, but three of them, P2, P3 and P4, showed
      significant promoter activity when they were respectively introduced into Musca
      domestica larva by electroporation. The two fragments, P5 (+684/+302) and P6
      (+165/+302), obtained by digesting P2 and P3 with Spe I and Hind III, were also
      subcloned into pGFP vector, and they showed no promoter activity in Sf9 cells,
      BHK -21 cells and Musca domestica larva. The results demonstrated that the core
      promoter spanned 302bp and contained a CCAAT box and a TATA box upstream
      translation initiation codon (ATG), but itself had no transcriptional activity,
      and that regulatory promoters or enhancers and other cis-elements presented from
      +302 to +1616 were necessary to maintain the specific expression.

PMID- 15473321
TI  - [Study on the calculation methods of confidence intervals of genetic parameter
      estimates by method R and number of repeating estimations].
AB  - The objective of the study was to probe the calculation methods of confidence
      intervals of genetic parameter estimates by Method R and influences of number of
      repeating estimations (NORE). Four models were used to generate the datasets by
      simulation. The datasets originated from 200 sires and 2 000 dams and simulation
      progressed by BLUP( Best Linear Unbiased Prediction) selection for five
      overlapping generations. Variance components were estimated by using multivariate
      multiplicative iteration (MMI), combined with preconditioned conjugate gradient
      (PCG) to solve the mixed model equations. Parameter estimates and their standard
      errors and confidence intervals were computed by classical method, classical
      method after Box-Cox transformation and bootstrapping. The results showed that
      when NORE was larger, all three methods were feasible, but when NORE was fewer,
      bootstrapping was recommended. Fewer NORE was feasible under simple models, but
      more NORE was needed for complex models. Direct heritabilities were overestimated
      with the increase of number of random effects, but underestimation was found for
      many parameters with the increase of iteration numbers of PCG and MMI.

PMID- 15473322
TI  - Inheritance and QTL mapping of low temperature germinability in rice (Oryza
      sativa L.).
AB  - Quantitative trait loci (QTL) controlling low temperature germinability (LTG) in
      rice were identified using 81 recombinant inbreed lines (RILs) derived from a
      cross between a japonica variety Kinmaze and an indica variety DV85. The accurate
      condition of LTG evaluation was assumed at 15 degrees C for 10 d after removing
      the effect of dormancy and the second dormancy. By setting check, the scores of
      LTG in this study were evaluated. The germination rate at 15 degrees C for 10 d
      was scored to represent the LTG. The LTG of the RILs ranged from 0 to 99%. By
      single point analysis, simple interval mapping, and composite interval mapping, 5
      putative QTL, qLTG-2, qLTG-6, qLTG-7, qLTG-LTG-11 and qLTG-12 were detected on
      chromosomes 2, 6, 7, 11 and 12 respectively. At the regions of qLTG-2, qLTG-6 and
      qLTG-11, DV85 alleles increased the LTG, while Kinmaze alleles increased it at
      the regions of qLTG-7 and qLTG-12. Among the five QTLs reported here, qLTG-2,
      qLTG-7 and qLTG-12 were newly detected, while the other two QTL-containing
      regions were close to those previously reported. Epistatic QTL were also detected
      in this paper.

PMID- 15473323
TI  - Genetic analysis of rice varietal diversity for rice blast control.
AB  - Two Indica hybrid rice of Shanyou63 (A) and Shanyou22 (B), two glutinous
      landraces of Huanghenuo (C) and Zinuo (D) and three improved Japonica rice of
      Hexi41 (E), Chujing12 (F) and 8126 (G) were selected and their genetic resistance
      relationship was estimated using resistance gene analogue (RGA). The results
      showed that there were similar genetic relationships between hybrid varieties at
      the genetic similarity (GS) of 0.86,and among improved Japonica varieties at the
      GS of 0.84, while highly genetic diversifications between traditional varieties,
      Indica and Japonica varieties, traditional and modern variety ( GS:0.45). The
      results also showed that clustering analysis based on RGA data were generally
      corresponded to known pedigrees and blast field resistances of the varieties.
      Based on varietal differences in RGA data and agronomic traits, plot experiments
      of five mixed-planting combinations of A/C, A/D, B/C, B/D and A/B and two
      combinations of E/C and E/F/G were conducted in Jianshui and Shiping counties (
      Indica rice growing region) and Luxi County (warm Japonica region) in Yunnan
      Province in past two years, respectively. The results demonstrated that rice
      blast management was more effective in five mixed-planting combinations of
      varieties with different genetic backgrounds (GS: 0.45-0.77) than in two
      combinations with similar genetic relationships (GS: 0.84-0.90), compared with
      their monocultures. It is evident for the highly susceptible landraces in mixed
      planting to achieve disease control, with significant decreases both in incidence
      and severity. The blast control efficiencies of landraces in different mixture
      combinations reached to 54.47%-92.18%. The control efficiencies of improved
      varieties varied from 15.12% to 25.54% in mixture combinations with closed
      genetic relationship. In addition,the total yield of 5 varietal combinations with
      distant genetic relationship increased 539.0-904.0 kg/ha in the mixed-planting
      plots, at increase rates of 5.6%-10.2%. Mixed rice varieties with similar genetic
      background did not achieve significant yield increase. Otherwise, the yield of
      E/F/G decreased 2.7%-4.0% compared with pure stand. The results can provide
      scientific basis of varietal combinations in diversification experiments for
      blast control.

PMID- 15473324
TI  - [QTL analysis for lodging resistance in rice using a DH population under lowland
      and upland ecosystems].
AB  - A DH (doubled haploid) population derived from a cross between Japonica upland
      rice IRAT109 and Japonica paddy rice Yuefu,was used in this study. Three culm
      traits, basal culm thickness(BCT), culm length (CL) and culm strength (CS), of DH
      lines and their parents under upland and lowland ecosystems at milk stage were
      studied. There were very significant positive correlations between BCT and CL,
      between BCT and CS and between CL and CS. Data from upland and lowland ecosystems
      were analyzed respectively and jointly, based on a constructed molecular linkage
      map(including 94 RFLP markers and 71 SSR markers and covering 1 535. 1cM)and the
      software QTLmapper version 1.0. A total of nine additive QTLs and five pairs of
      epistatic QTLs associated with BCT, CL, and CS were found by data analysis
      respectively. Six additive QTLs and six pairs of epistatic QTLs associated with
      BCT and CL were detected by data analysis jointly. Six additive QTLs and one pair
      of epistatic QTLs were detected by both methods. Two additive QTLs and two pairs
      of epistatic QTLs ( bct1a, c/9, c/6a-c/6c and cs5-cs12) for culm traits with
      general contributions of over 30% to phenotypic variation might be useful for
      upland rice lodging resistance molecular breeding under upland ecosystem.

PMID- 15473325
TI  - [Mapping of a new resistance gene to bacterial blight in rice line introgressed
      from Oryza officinalis].
AB  - Rice line 'B5', which was derived from the wild rice Oryza officinalis Wall ex
      Watt through introgression, has been proved to be high resistant to brown
      planthopper, whitebacked planthopper and bacterial blight (Xanthomonas oryzae pv.
      oryzae). In this study, the resistance to bacterial blight of 187 recombinant
      inbred lines (RILs) from a cross between ' B5' and 'Minghui63' were evaluated and
      RFLP markers linked to the resistance gene were identified by bulked segregant
      analysis. Analysis of the molecular marker linkage map and the data of the lesion
      length of RILs located the resistant gene within a 1. 3 cM region flanked by RFLP
      markers C904 and R596 on chromosome 1. This locus contributed to 52.96% of the
      phenotypic variance of resistance in the population, and is considered to be a
      new locus as compared with other resistant genes to bacterial blight that have
      been reported. We tentatively designate this gene as Xa29(t). This newly tagged
      gene introgressed from wild rice is valuable to molecular marker-assisted
      selection for multiple resistant materials in rice breeding programme.
      Furthermore, it provides information for cloning the resistant gene Xa29(t) in
      rice.

PMID- 15473327
TI  - [Identification of the triploid hybrid chromosomes of Elymus canadensis L. x
      Hordeum brivisubulatum Link. by genomic in situ hybridization].
AB  - AThe intergeneric F1 hybrid between Elymus canadensis L. and Hordeum
      brivisubulatum Link. is a triploid (2n = 3x = 21 ), in which 7 chromosomes,that
      is equal to the base number of parent's chromosomes, were lost. In order to
      indentify the chromosome constitution of the triploid F1 hybrid of E. canadensis
      L. x H. brivisubulatum Link., the genomic in situ hybridization of F1 root tip
      cell chromosome DNA that H. brivisubulatum H1 H1 H2H2 genome DNA labeled with
      Biotin-16-dUTP was conducted using E. canadensis SSH(c)H(c) genome as blocking
      DNA. The result showed that the chromosomes of triploid F1 hybrid consisted of 7
      chromosomes from E. canadensis S genome and 14 chromosomes from H. brivisubulatum
      H1 H2 genome while the 7 chromosomes of Hc genome of E. canadensis were lost.

PMID- 15473326
TI  - [Identification of wheat and barley hybrid offspring by GISH and PAGE].
AB  - Genomic in situ hybridization (GISH) and polyacrylamide gel electrophoresis
      (PAGE) of wheat seed were used to identify the barley chromosome in offspring of
      wheat and barley hybrid. A sires of alien addition lines, alien substitution
      lines and translocation lines were detected by GISH. WBA984 and WBA9812 were
      alien addition lines, WBS0215 and WBS0264 were alien substitution lines,and
      WBT02125 and WBT02183 were translocation lines in chromosome terminal. SDS-PAGE
      analysis and A-PAGE patterns indicated that WBA9812 were 5H alien addition line,
      WBS0264 was 1 B/5H alien substitution line, and WBT02125 was 1 BL/5HL
      translocation line.

PMID- 15473328
TI  - [Cloning and heterologous expression of a novel delta6 -desaturase gene from
      Rhizopus arrhizus NK030037].
AB  - A 593 bp DNA fragment was amplified from Rhizopus arrhizus NK030037 with
      degenerate oligonucleotide primers designed based on the sequences information
      for fungi delta6-fatty acid desaturase genes by RT-PCR and sequenced. Gene
      specific primers derived from this partial sequence were used for the
      amplification of the 3'- and 5'-ends of this cDNA by RACE method, and this lead
      to a full-length cDNA sequence of 1 482 bp was amplified. Sequence analysis
      showed this cDNA sequence had an open reading frame(ORF) of 1 377 bp coding 458
      amino acids of 52 kD. The deduced amino-acid sequence of the ORF showed
      similarity to those of the above delta6-fatty acid desaturases which comprised
      the characteristics of membrane-bound desaturases, including three conserved
      histidine-rich boxes and hydropathy profile. A cytochrome b5-like domain was
      observed at the N-terminus. The full-length cDNA sequence is a putative novel
      delta6-fatty acid desaturase gene. To elucidate the function of the protein, two
      specific primers corresponding to the nucleotide sequences of start and stop
      codons were used to amplify the coding sequence. The amplified cDNA RAD6 was
      subcloned into the expression vector pYES2.0 to generate a recombinant plasmid
      pYRAD6, which was subsequently transformed into Saccharomyces cerevisiae strain
      INVScl for heterologous expression by lithium acetate method. Grown to
      logarithmic phase at 30 degrees C, the transformed cells were supplemented with
      0.5 mmol/L. Linoleic acid and induced by 2% galactose for a further 48 h of
      cultivation at 20 degrees. Total fatty acids were extracted from the induced
      cells and subjected to methyl-esterification. The resultant fatty acid methyl
      esters(FAME) were analyzed by gas chromatography(GC). A novel peak corresponding
      to gamma-linolenic acid (GLA) methyl ester standards was detected with the same
      retention time, which was absent in the cell transformed with empty vector. The
      percentage of this new fatty acid to total fatty acids was 3.85%. Gas
      chromatography-mass spectrometry( GC-MS) analysis of this fatty acid methyl
      derivative demonstrated that the novel peak was GLA methyl ester. These results
      showed that the transgenic product exhibited delta6-fatty acid desaurase
      activity, converting LA to GLA specifically.

PMID- 15473329
TI  - [Development of retrovirus-mediated insertional mutagenesis in zebrafish and its
      application in saturation mutagenesis and gene screening].
AB  - The strategies of large-scale mutagenesis and gene screening include chemical
      mutagenesis, insertional mutagenesis and gene trap. Insertional mutagenesis is a
      method for identifying genes by using the integration of DNA as the mutagen,
      thereby facilitating the cloning of the mutated gene. The use of retrovirus
      mediated insertional mutagenesis in zebrafish has led to the mutation and rapid
      identification of hundreds of genes required for embryonic development and cell
      growth. Gene trap elements are also used in the construction of retrovirus
      vectors. The whole system is likely to make zebrafish the first vertebrate to
      achieve saturation mutagenesis and gene screening.

PMID- 15473330
TI  - Tea tree oil: cutaneous effects of the extracted oil of Melaleuca alternifolia.
AB  - The use of botanical extracts for their perceived therapeutic benefits has gained
      increased popularity in this country and abroad. In particular, tea tree oil (the
      extracted oil of Melaleuca alternifolia) has gained widespread use for its
      purported antimicrobial and therapeutic effects. In parallel with this increased
      use is an expanding series of reported adverse effects, including allergic
      contact dermatitis, systemic contact dermatitis, linear immunoglobulin A disease,
      erythema multiforme-like id reactions, and systemic hypersensitivity reactions.
      We present a review of tea tree oil with regard to its history, chemistry,
      purported medicinal uses, and possible adverse cutaneous effects.

PMID- 15473331
TI  - Prevalence of botanical extract allergy in patients with contact dermatitis.
AB  - BACKGROUND: Botanical extracts are used widely in over-the-counter products. They
      are primarily added for fragrance and their purported healing properties.
      Numerous case reports of allergic contact allergy to botanical extracts have been
      published; however, little is known regarding the prevalence of allergic
      reactions to botanical extracts. OBJECTIVE: To determine the prevalence of
      allergic patch-test reactions to a collection of botanical extracts in patients
      referred for patch testing. METHODS: A total of 140 patients were patch-tested to
      a study tray containing 47 botanical extracts. Patients were divided into two
      groups: (1) a high-risk group consisting of 21 patients with a clinical diagnosis
      of contact allergy who were using botanical products and whose contact dermatitis
      was not fully explained by testing to standard allergens and (2) a control group
      consisting of 119 patients with no history of botanical extract use and who were
      being evaluated in a contact dermatitis clinic. RESULTS: Ten of 21 patients
      (47.6%) in the high-risk group had at least one relevant botanical extract
      positive reaction. Only 4 patients (3.4%) in the control group had a relevant
      positive reaction. Four patients in the high-risk group had more than one
      relevant botanical reaction. Tea tree oil caused the most common relevant
      positive reaction. CONCLUSIONS: Contact allergy to botanicals was common in this
      highly selected group of patients. Contact dermatitis patients who use botanical
      products and whose reactions are not fully explained by standard patch testing
      may benefit from more extensive patch testing to botanical extracts.

PMID- 15473332
TI  - Occupational dermatitis in a milk industry worker due to Kathon CG.
AB  - The allergenic properties of the preservative Kathon CG have been well known
      since 1980. Kathon CG is regularly used in many industrial processes because of
      its germicidal powers. The most common sources of exposure for people are
      cosmetics and toiletries. Occupational contact dermatitis is unusual among milk
      industry workers because of the high level of factory automation.

PMID- 15473333
TI  - Recovery from mercury-induced burning mouth syndrome due to mercury allergy.
AB  - We report a case in which burning mouth syndrome (BMS) was associated with a
      strong allergy to mercury. The aim of this case history is to strengthen
      knowledge of the relationship among allergy to mercury, systemic allergic contact
      dermatitis, and hypersensitivity of the oral mucosa. We performed series of
      standard and dental patch tests for screening for contact allergy to dental
      materials, in accordance with International Contact Dermatitis Research Group
      guidelines. Positive extreme allergic reactions to mercury (+++) and amalgam (++)
      were seen at the patch site and caused a flare-up of the systemic erythematous
      reaction. Full recovery from BMS and complete remission of systemic dermatitis
      were achieved after the mercury tooth filling was removed. Mercury is thought to
      be an allergen implicated in BMS as well as in the systemic reactivation of
      allergic contact dermatitis. Patch testing with dental series seems to have
      greater sensitivity and relevance in BMS patients.

PMID- 15473334
TI  - Contact allergy to progesterone and estradiol in a patient with multiple
      corticosteroid allergies.
AB  - A 61-year-old woman with a persistent hand and foot dermatitis developed multiple
      contact allergies to topical steroids. She had a past history of allergic contact
      dermatitis (ACD) to a hormone replacement patch containing both estrogen and
      progesterone. The aim of this report is to highlight the potential cross
      reactions between topical corticosteroids and sex steroids. Patch testing with a
      standard series, a corticosteroid series, and the sex steroids progesterone and
      estradiol was performed. Positive ACD reactions to hydroxyprogesterone,
      progesterone, and estradiol occurred. There were also multiple corticosteroid
      allergies. This case demonstrates that patients who develop contact allergies to
      sex steroids are at risk of developing multiple corticosteroid allergies.

PMID- 15473335
TI  - Lymphocyte transformation testing for quantifying metal-implant-related
      hypersensitivity responses.
AB  - Hypersensitivity to metallic implants has been documented in case reports and
      cohort studies. However, this phenomenon remains unpredictable and poorly
      understood. There is continuing concern about the extrapolation of dermal patch
      testing to the periimplant environment. The utility of lymphocyte transformation
      testing (LTT) for predicting implant-related sensitivity in orthopedic patients
      was evaluated by contrasting LTT and patch-testing protocols and examining
      original cohort LTT data of subjects with and without implants. LTT of peripheral
      blood lymphocytes was performed, using four groups: (1) age-matched controls; (2)
      patients with osteoarthritis (preimplant), with and without dermal metal
      sensitivity; and (3) patients with total hip arthroplasty. A stimulation index of
      greater than 2 ( p < .05) indicated metal sensitivity. Patients with
      osteoarthritis and a history of metal sensitivity were more reactive to nickel
      than were those of any other group, as expected (ie, 66% incidence and average
      stimulation index of > 20). However, subjects with implants (group 3) were
      threefold more reactive to chromium (p < .04) than were controls (group 1) or
      subjects with osteoarthritis (group 2). Quantifiable lymphocyte reactivity as
      exemplified by increased incidence and average reactivity levels was metal
      implant specific (characteristic of adaptive immune responses) and suggests that
      LTT may be useful in the determination of implant-specific sensitivity.
      Advantages of LTT include quantitative results and the facilitation of
      multichallenge agent and dose testing. Thus, LTT (provided by laboratories fully
      disclosing testing methods) may be an additional tool in the armamentarium of
      physicians.

PMID- 15473336
TI  - Patch testing for corticosteroid allergy.
AB  - During the 1990s, contact allergy to topical corticosteroids became a well
      recognized complication of dermatologic therapy. Groups of related
      corticosteroids were subsequently identified on the basis of their chemical
      structures, and some investigators have found these helpful in identifying
      potential cross-reactions. The widespread use of hydrocortisone as an over-the
      counter medication and its addition to a wide array of topical products make
      hydrocortisone the most common allergen. Awareness of the risk of corticosteroid
      allergy and the availability of newer topical immunomodulating agents such as
      tacrolimus and pimecrolimus may eventually reduce the incidence of contact
      allergy to corticosteroids. Rokea el-Azhary, MD, PhD, Professor of Dermatology at
      the Mayo Clinic in Rochester, MN; Erin Warshaw, MD, Associate Professor of
      Dermatology at the University of Minnesota, Veterans Affairs Medical Center; and
      Kalman L. Watsky, MD, Associate Clinical Professor, Department of Dermatology,
      Yale University School of Medicine, and Section Chief of Dermatology, Hospital of
      Saint Raphael, were invited to give their opinions on strategies for detecting
      allergens and recommending allergen substitution for patients with suspected
      topical corticosteroid allergy.

PMID- 15473337
TI  - Straight advancement of epidural catheter--comparative assessments by method and
      site of epidural needle puncture and angle of puncture.
AB  - The catheter straight advancement rate for introduction into the epidural space
      was investigated using a radiopaque catheter. One hundred patients were divided
      into two groups and underwent thoracic or lumbar epidural punctures, with one of
      two different puncture methods: the median approach or paramedian approach. Two
      different angles of epidural puncture needle insertion, 50-60 degrees and 90
      degrees to skin surface plane, were used. A catheter was inserted into the
      epidural space about 5 cm cephalad and the course of the inserted catheter was
      ascertained by radiography. The results have shown that punctures performed at an
      insertion angle of 50-60 degrees yielded higher catheter straight advancement
      rates than those performed at an angle of 90 degrees in both thoracic and lumbar
      epidural punctures.

PMID- 15473338
TI  - An anti-K-ras ribozyme suppresses oncogene expression and cell growth of human
      pancreatic cancer.
AB  - Hammerhead ribozymes are effective modulators of gene expression due to their
      simple structure, site-specific cleavage activity and catalytic potential. The K
      ras oncogene is thought to play an important role in the growth of pancreatic
      cancer, because an activated (mutated) ras gene is found in approximately 90% of
      human pancreatic cancers. In this study, we designed a hammerhead ribozyme
      directed against K-ras mRNA at codon 25 [K-ras Rz (25)], and investigated its
      efficacy in a cultured human pancreatic carcinoma cell line, MIA PaCa-2. K-ras Rz
      (25) significantly reduced the cellular K-ras mRNA level when introduced into the
      MIA PaCa-2 cells. The ribozyme suppressed cell growth. K-ras Rz (25) appears
      capable of reversing the malignant phenotype in human pancreatic carcinoma cells.

PMID- 15473339
TI  - Uterine body cancer mass screening at Tokai University Hospital.
AB  - A total of 1,512 women participated in mass screenings for uterine body cancer
      (UBC) from 1998 to 2003 at Tokai University Hospital. Their rate in the examinees
      of uterine cervical cancer (UCC) mass screenings was 4.7%. Among the 1,512
      examinees, endometrial cytological abnormalities (class III or higher) were found
      in 17 (1.1%) cases. As a result, UBC was detected in two patients (0.13%). One
      case was diagnosed as class V, adenocarcinoma, and she underwent hysterectomy. In
      another case, adenocarcinoma was found to be associated with atypical endometrial
      hyperplasia in hysterectomy specimens. For the remaining 15 cases diagnosed as
      class III, the cytological abnormalities disappeared after a follow-up except for
      3 patients who were not followed at Tokai University Hospital. In a comparison of
      the examinees with or without genital bleeding, the cytological abnormalities
      were more frequently detected in the former group; 4.2% (6/142) vs. 0.6% (5/819)
      (p < 0.05). We recommend examinees aged 40 years or higher with a complaint of
      genital bleeding to participate in UBC mass screening for detection of
      endometrial adenocarcinoma at early stages.

PMID- 15473340
TI  - A case of atypical benign fibrous histiocytoma.
AB  - A case of atypical benign fibrous histiocytoma is reported. A 62-year-old
      Japanese female visited our clinic because of an asymptomatic solitary lesion on
      the skin of the left leg. Physical examination revealed a polypoid mass lesion
      (2.5 x 2.3 x 1.8 cm) with central erosion. The lesion began with a 1 mm-sized
      papule and slowly enlarged over the 20 years. Clinical diagnosis was a malignant
      tumor such as dermatofibrosarcoma protuberans, atypical fibroxanthoma or adnexal
      tumors. Biopsy of the polypoid lesion was carried out. Histopathological
      examination revealed a polypoid lesion consisting of proliferation of fibroblast
      like spindle cells in the dermis. Large atypical cells with pleomorphic nuclei
      were occasionally observed but mitotic figures were rare. From
      immunohistochemical results (CD68, Factor-XIII, MIB-1 labeling index), we
      diagnosed this case as "atypical benign fibrous histiocytoma (ABFH)". Clear
      distinction has not been made between ABFH, a variant of benign fibrous
      histiocytoma, and atypical fibroxanthoma, which is a variant of malignant fibrous
      histiocytoma. Here we report a case of ABFH with a diagnosis of the neoplasm.

PMID- 15473342
TI  - Notice of duplicate publication.

PMID- 15473341
TI  - Multiple organ dysfunction in congenital murine toxoplasmosis.
AB  - Infection of gravid Nya: NYLAR (NYLAR), C57BL/6J (C57), and BALB/c mice with
      Toxoplasma gondii, on gestation day 7, resulted in fetal resorptions, abortions,
      and stillbirths. Fetal wastage (estimated) was 35 and 40% in the NYLAR and C57
      strains and 55% in the BALB/c strain. Postnatally, pups were cachectic and growth
      retarded, with some developing hind limb weakness, petechial lesions on ears and
      tail, and a blood-tinged nasal exudate. Only 13 of 97 BALB/c pups, 14 of 41 C57
      pups, and 46 of 153 NYLAR pups survived the first month of life. At necropsy,
      swollen, blotched livers, enlarged spleens, pallid kidneys and pulmonary
      hemorrhages were observed. Cysts of T. gondii were detected in every pup, via
      press-smears of brain. Histologic examination revealed mineralizing cavitations,
      ventricular deformations, and periventricular edema in the central nervous
      system; extensive liver pathology marked by hepatocellular necrosis and
      calcification, sinusoidal dilatation, and giant cell granulomas; congestion of
      the spleen with blurring of red and white compartments and cavitations in the
      white pulp; and tubule and glomerular necrosis and calcification in the kidney.
      The pulmonary hemorrhages and dermal petechial lesions may reflect a bleeding
      diathesis due to hepatic insufficiency. The pathogenesis of congenital
      toxoplasmosis, in the 3 strains of mice, appears due to microvascular dysfunction
      characterized by dysregulation of hemostasis, perfusion failure, and multiple
      organ dysfunction, rather than to parasite-mediated cytopathology. We suggest
      that hematogenous dissemination and endothelial invasion by the parasite induced
      a systemic inflammatory response syndrome (i.e; toxoplasmic sepsis) leading to
      the microvascular dysfunction.

PMID- 15473343
TI  - The usefulness of the blink reflex in the early diagnosis of cranial nerve
      neuropathy associated with diabetes mellitus.
AB  - BACKGROUND: Electrophysiological testing can be of value in early diagnosis of
      diabetic neuropathy. Limited data is available in the use of the blink reflex
      (BR) in diabetes mellitus (MD). AIM: is to evaluate the efficacy of BR in early
      diagnosis of cranial nerve neuropathy in DM. MATERIALS AND METHODS: 67 diabetes
      and 32 healthy controls-age and sex matched- were chosen. The diabetes were of
      type I and type II and of more than or less than 10 years duration. The BR was
      elicited by stimulation the supraorbital nerve using the Dantec Neuromatic 2000M
      machine. The latency of the components response recorded as R1, R2y (ipsilateral)
      and R2c (contralateral). A direct response was achieved by the stimulation of the
      facial nerve; a square wave of 200 msec. was used. RESULTS: No differences were
      noted when the two sides were compared in diabetic patients, while the difference
      was highly significant in the increased latency of R1, R2y and R2c each type of
      diabetes as compared to the control. Comparison of the types and duration of
      diabetes between each other showed no significant difference. Direct measurement
      of the latency response of the facial nerve gave a response in diabetics of both
      types and duration. CONCLUSION: the BR can be useful in the early diagnosis of
      diabetic neuropathy.

PMID- 15473344
TI  - The feline fictive startle response and its related potential in the
      pedunculopontine nucleus.
AB  - The human P1/P50 midlatency auditory evoked potential and the auditory startle
      response (SR) have been used for investigating sensory gating and sensorimotor
      modulation which is impaired in various psychiatric diseases. In the present
      study, we demonstrated that auditory stimulation was capable of eliciting
      excitation of flexor and extensor neurograms from the hindlimb nerves in the
      paralyzed decerebrate cat, a phenomenon which corresponds to a "fictive" startle
      response (FSR). Previous studies have shown that the SR consists of distinct
      excitatory components, "early" and "late", separated by an inhibitory phase.
      However, in the FSR, unlike the SR in the intact preparation, the "late"
      excitatory phase never occurred. Recordings from the pedunculopontine nucleus
      (PPN) simultaneously with the FSR revealed the presence of an auditory evoked
      potential at a 20-25 ms latency, presumably the depth-recorded equivalent of the
      vertex-recorded wave A, which has been shown to be the feline equivalent of the
      human P1 potential. The depth-recorded wave A appeared to share neurological
      substrates with the excitatory phase of the FSR, since both responses were
      facilitated in a similar manner by increasing stimulus duration. We previously
      reported that, in the intact rat, the vertex-recorded P13 potential, the putative
      rodent equivalent of the human P1 potential, is generated, at least in part, by
      outputs of the PPN, and that the P13 potential shares neurological substrates
      with the "early" excitatory phase of the SR. Taken together, the results of the
      present study indicate that, along with the SR and the P13 potential in the
      intact rat, the FSR and the depth-recorded wave A in the paralyzed cat may be
      unique animal models for further examining, in the absence of neural structures
      rostral to the precollicular decerebration, the cellular basis of startle
      behavior.

PMID- 15473345
TI  - Knee muscular response strategies differ by developmental level but not gender
      during jump landing.
AB  - The purpose of this investigation was to determine differences between pre- and
      post-pubescent males and females in quadriceps (vastus medialis; VM) and
      hamstrings (medial hamstrings and biceps femoris; HAMS) muscular activation
      patterns via the root mean square of surface electromyography (SEMG) during self
      initiated vertical jump landing. Fifty-eight subjects, divided into age and
      gender groupings, were compared on kinematic variables during pre-landing (100
      msec preceeding initial ground contact), post-landing (100 msec following initial
      ground contact), and initial-contact-to-maximum-knee-flexion stages. Kinematic
      variables investigated were (1) SEMG values during each stage of the vertical
      jump landing; (2) Co-contraction ratios (CCR), which represented the ratio of
      normalized hamstrings' activity to normalized quadriceps' activity; and, (3) knee
      angle at initial contact. Results indicated (1) no significant gender differences
      in variables measured; and, (2) significant developmental level differences. Post
      pubescent subjects displayed greater HAMS acitivity and CCR values in the pre
      landing stage relative to post-landing stages, indicating that post-pubescent
      subjects had a greater level of hamstrings co-contraction prior to landing than
      pre-pubescent subjects. Conversely, pre-pubescent subjects displayed greater post
      landing and initial-contact-to-maximum-knee-flexion ratios, indicating a greater
      level of hamstrings' co-contraction during post-landing stages than post
      pubescent subjects. There were no significant differences in knee angle at
      initial contact. The greater level of hamstrings' co-activation prior to landing
      by post-pubescent subjects indicated that they used a strategy of pre-tuning the
      hamstrings prior to landing (more CNS pre-activation) to control the ground
      reaction forces and anterior tibial displacement experienced by the knee during
      landing. On the other hand, pre-pubescent subjects controlled these forces by
      having a greater level of hamstrings' co-activation during landing, which
      represents more of a reflexive activation in response to ground impact.

PMID- 15473346
TI  - Ulnar neuropathy at the elbow: predictive value of clinical and
      electrophysiological measurements for surgical outcome.
AB  - The aim of this study was to identify factors predictive of complete relief of
      symptoms in subjects with ulnar neuropathy at the elbow (UNE), undergoing
      surgical release. Clinical and electrophysiological results of 19 consecutive
      cases of UNE belonging to 18 patients (mean age 50.6 years, range 28-73)
      undergoing simple decompression were reviewed retrospectively. After surgery,
      seven cases were free of symptoms, nine showed improvement and three were
      unchanged. In all cases there was significant postoperative improvement of almost
      all nerve conduction values. Only preoperative sensory action potential amplitude
      of the ulnar nerve stimulating the little finger ( U5 SAP) was predictive of
      postoperative symptom free outcome. The other electrophysiological measures, age
      of patients, sex, presencelabsence of carpal tunnel syndrome, preoperative
      clinical stage and duration of symptoms were not predictive of excellent outcome.
      Preoperative U5 SAP amplitude was found to be a good predictor of disappearance
      of symptoms after UNE surgery. The probability of normalising
      electrophysiological values after surgery (U5 SAP amplitude, motor conduction
      velocity difference between across elbow and below elbow to wrist segments)
      depended on their preoperative values. Only the moderately anomalous values
      returned in the normal range.

PMID- 15473347
TI  - Threshold intensity and central motor conduction time in patients with monomelic
      amyotrophy: a transcranial magnetic stimulation evaluation.
AB  - OBJECTIVE: To determine the Cortical threshold intensity (TI) and central motor
      conduction time (CMCT) in patients with monomelic amyotrophy (MMA). METHODS: TI
      and CMCT were evaluated by means of transcranial magnetic stimulation in 18
      patients of MMA and 12 healthy controls at the clinical neurophysiology
      laboratory, department of neurology, All India Institute of Medical Sciences, New
      Delhi. RESULTS: The mean age of patients was 23.6 (SD 6. 7) years and of controls
      was 24.3 (SD 3.2) years (p > 0. 05). The mean TI in patients was 60.83% (SD
      11.28) on ipsilateral and 60% (11.5%) on contralateral cortex stimulation. In
      controls, the mean TI was 66.67% (SD 11.5) on one side and 65% (11.87%) on
      contralateral cortex stimulation. There was no significant difference in the TI
      between these two groups (p > 0.05). The mean CMCT in patients was 8.3 (SD 1. 7)
      ms on ipsilateral and 9.4 (SD 1.6) ms on contralateral cortex stimulation (p >
      0.05). In controls CMCT was 8.3 (SD 1.8) ms on one side and 8.6 (SD 1.4) ms on
      contralateral cortex stimulation. Upper limit of normal CMCT was 12.7 ms.
      CONCLUSIONS: As compared to controls there was no significant abnormality in TI
      and CMCT was normal in all except two patients where it was marginally prolonged.
      This could be because of excessive loss of anterior horn cells.

PMID- 15473348
TI  - Conduction block--the diagnostic value in the early stage of Guillain-Barre
      syndrome.
AB  - Immune-mediated segmental demyelination is the basic pathomorphological substrate
      of the Guillain-Barre syndrome (GBS). The aim of the study is to determine the
      diagnostic value of the conduction block in the early stage of GBS, as well as
      its changes during of the development of the disease. Sixteen patients with GBS
      were examined. Electroneurography (motor nerve conduction studies) was performed
      at interval from the third day of the onset till the first year. Partial CB in
      the early stage of the disease (range 0-15 days) was registered in 81,2% of the
      patients. In demyelinating forms of GBS partial CB was determined in 61% of the
      investigated nerves. It is the most often observed in peroneal nerves, followed
      by tibial, ulnar and median nerves in the same order. The maximal reduction of
      the amplitude of the CMAP (maximal CB) was registered before the 30th day from
      the onset of the disease with following recovery on the sixth month and first
      year. Partial CB is more often observed in the early phase of GBS, when it could
      be the only sign of demyelination. When patients reached a clinical plateau,
      progressive slowing of motor nerve conduction and increasing CB were registered.
      Proximal CB was revealed more often than distal CB, because of the typical
      initial localization of the process. In the early phase of GBS, proximal CB is
      most often found in lower limbs (in peroneal nerve, followed by tibial nerve). In
      patients with axonal damage, CB was more severe than in demyelinating group.
      Partial CB is an important diagnostic criterion for segmental demyelination,
      which helps for confirming the diagnosis of early GBS, when conduction velocity
      and other electrodiagnostic criteria for demyelination are normal.

PMID- 15473349
TI  - Passive movement of hip and knee joints decreases the amplitude of soleus H
      reflex in stroke patients.
AB  - OBJECTIVES: The study aims to investigate the changes of the H-reflex in soleus
      (Sol-H-reflex) during hip and knee joint movements in stroke patients. METHODS:
      The experiments were carried out on five stroke patients with spastic hemiplegia
      (2 males and 3 females, 48 to 71 years old). Sol-H-reflexes were measured 200
      times for each joint movement speed Stimulus was given at random intervals (4 to
      5 seconds) during the joint movement. Two movement speeds were used to
      investigate the effects of movement speed. RESULTS: For both fast and slow
      movements, the amplitude of the Sol-H-reflex decreased in the middle flexion
      phase. In contrast, the amplitude of the Sol-H-reflex increased in the middle
      extension phase. For the fast movement, the Sol-H-reflex was smaller in only a
      small angle range during the flexion and extension phase in comparison to the
      slow movement. The Sol-H-reflex during the flexion phase was significantly
      smaller than during the extension phase at almost all angles for both speeds. The
      Sol-H-reflex for both speeds was smaller than the Sol-H-reflex at rest for the
      whole angle range. CONCLUSION: These results demonstrate the differential effects
      of Sol-H-reflex modulation in stroke patients when compared with normal subjects.

PMID- 15473350
TI  - Laryngeal electromyography: contribution to vocal fold immobility diagnosis.
AB  - Laryngeal Electromyography (LEMG) is a diagnostic test commonly used in patients
      with vocal fold movement disorder. The aim of this study is to describe LEMG in
      patients with vocal fold immobility. A total of 55 dysphonic patients with vocal
      fold immobility diagnosed by laryngeal endoscopy were grouped according to
      probable clinical cause: 1) unknown; 2) traumatic; or 3) tumoral compression.
      They were submitted to LEMG by percutaneous insertion of concentric needle
      electrode. LEMG was conclusive in all patients and showed a majority with
      peripheral nerve injury. LEMG diagnosed peripheral nerve damage in 25 group 1, 12
      group 2, and 11 group 3 patients. LEMG was normal in 4 patients, suggesting
      cricoarytenoid joint fixation. Central nervous system disorders was suggested in
      2 and myopathic pattern in 1. As the major cause of vocal fold immobility is
      peripheral nerve damage, LEMG is an important test to confirm diagnosis.

PMID- 15473351
TI  - Unilateral diaphragmatic paralysis following thoracic outlet surgery: a case
      report.
AB  - In this report, a young female, who initially presented with left upper extremity
      pain, eventually underwent surgery for presumed thoracic outlet syndrome.
      Following surgery, she developed shortness of breath. Diagnostic studies revealed
      an elevated left hemidiaphragm secondary to injury to the phrenic nerve.

PMID- 15473352
TI  - Diagnosing mild Carpal Tunnel Syndrome with interpolation.
AB  - Carpal Tunnel Syndrome (CTS) is the most common peripheral nerve entrapment. In
      the diagnosis of Carpal Tunnel Syndrome, velocity is determined by either
      measuring the average velocity over a segment by dividing the distance by the
      difference in latencies. Polynomial interpolation can determine the velocity at
      any point along a nerve. Applying interpolation techniques correctly classified
      58/60 electrophysiologically proven CTS cases (96.7%) and 36/38 normals (94.7%).
      Of 7 cases with CTS by standard sensory criteria alone, 6 (86%) had abnormal
      motor conduction using the interpolation technique. This shows that interpolation
      techniques can improve diagnostic accuracy in CTS. It also indicates that there
      is motor involvement in most cases of CTS, including a majority of cases
      previously classified as only sensory involvement.

PMID- 15473353
TI  - Assessment of Candida albicans genes expressed during infections as a tool to
      understand pathogenesis.
AB  - Candida albicans is the most common fungal opportunistic pathogen of humans and
      causes mucocutaneous, bloodstream and deep organ infections. Screening for C.
      albicans genes that are preferentially expressed within infected hosts represents
      a strategy to identify novel virulence factors and define global expression
      patterns relevant to pathogenesis. Until recently, C. albicans has not been
      amenable to screening using existing technologies. This has begun to change with
      the development of new molecular genetic tools and the sequencing of the C.
      albicans genome. In this paper, we review studies using recently developed
      techniques to identify genes expressed by C. albicans during infections, as well
      as work from our laboratory using a human antibody-based strategy. Along with
      others, we have shown that selected in vivo expressed genes encode known and
      previously unrecognized candidal virulence factors. Future studies in this area
      will identify additional novel virulence factors, as well as advance our
      understanding of pathogenesis.

PMID- 15473354
TI  - Safety aspects of working with Candida albicans-infected mice.
AB  - When the opportunity arose in the course of four experiments with mice and one
      with guinea pigs, all systemically infected with Candida albicans, the animals'
      bedding, work surfaces, surrounding walls, the balance pan and tools used in
      homogenization of tissues were sampled with contact plates or by water washing
      for the presence of viable C. albicans cells. Although substantial viable counts
      of C. albicans were measured in homogenized samples of kidneys and other tissues,
      no colonies of the fungus were recovered at any time from the work surfaces,
      walls or homogenizer stand. Contact samples of the homogenizer dispersal tool
      made on four occasions during the course of 24 successive homogenizations showed
      that few viable C. albicans could be cultured from the tool after two water
      washes, and none at all after two washes with 70% ethanol. Water samples of the
      contents of three cages that had housed infected mice were all negative for
      viable C. albicans, however, direct contact plate samples of the bedding material
      and excreta in seven cages yielded positive cultures with colony counts from 1 to
      8 per sample in five instances and 18 in one instance. It is concluded that the
      potential infection risk to personnel of working with this hazard group 2 fungus
      is minimal and the highly stringent safety regulations for all organisms in
      hazard group 2 may err on the side of over-caution.

PMID- 15473355
TI  - Development of a novel, simple and rapid molecular identification system for
      clinical Candida species.
AB  - Identification of clinical yeast isolates causing candidiasis is routinely
      performed by commercial yeast identification systems based on biochemical,
      morphological and physiological tests. These systems require 3-5 days and the
      proportion of identifications that are incorrect is high. Our novel and rapid
      molecular identification system for clinical Candida species is based on the
      analysis of restriction patterns obtained from PCR-generated ribosomal DNA
      sequences using five restriction enzymes. A software package (CandID) was
      designed to include a database of restriction fragment length polymorphism (RFLP)
      patterns for 29 Candida species. For 'in-house' validation, 122 clinical isolates
      that had previously identified in clinical laboratories were typed by this
      system. These clinical isolates were also independently re-identified by the API
      20C AUX system. The ribosomal DNA RFLP database in the context of supporting
      analytical software allowed simple and rapid (1 work day) identification.

PMID- 15473356
TI  - Immunogenicity and protective effect of recombinant enolase of Candida albicans
      in a murine model of systemic candidiasis.
AB  - Enolase, a 46-kDa glycolytic enzyme, is an immunodominant antigen of the
      opportunistic pathogen Candida albicans. A recombinant 6 x His-tagged enolase was
      studied, in conjunction with interleukin-12 (IL-12), as an adjuvant for cytokine
      induction favouring protection in a murine model of haematogenous candidiasis.
      Mice immunized with enolase plus IL-12 showed increased antibody titres against
      enolase, as well as increased median survival time and decreased fungal burden in
      kidneys, in comparison to non-immunized or IL-12-treated mice. This increased
      survival was attributable to enolase-induced cell-mediated immunity as it also
      occurred in B-cell-deficient mice. Enolase immunization stimulated a predominant
      T-helper-1 (Th1) cytokine pattern in splenic cells and induced production of
      interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) by purified CD4+ T cells.
      However, despite the elevation of immunogenicity, recombinant enolase induced
      only a modest protection against disseminated candidiasis, suggesting a form of
      protection likely attributable to the induction of a Th1 cell-mediated immune
      response.

PMID- 15473357
TI  - Oxy2 as a transcriptional activator gene for copper uptake in Cryptococcus
      neoformans.
AB  - Cryptococcus neoformans is subject to oxidative attack by host immune cells;
      consequently, oxidant-resistant mechanisms may be important in pathogenesis.
      Mutations at the OXY2 locus confer decreased laccase and increased sensitivity to
      hyperbaric oxygen in the background of the oxyl mutation, but, alone, do not
      confer sensitivity to oxidants. Because metal deficiency can potentiate or
      ameliorate sensitivity to oxidants, and because the melanin-synthesizing laccase
      contains copper, we investigated copper acquisition in an oxy2 mutant. We found
      that its external Cu/Fe reductase activity was lower than that of wild type, and
      although copper deprivation induced the reductase in the wild type, it did not do
      so in oxy2. Oxy2 is sensitive to copper chelation but resistant to high copper,
      suggesting that copper transport is decreased. The strain expresses large amounts
      of alternate oxidase in response to Cu-chelation, perhaps in response to
      defective, Cu-deprived cytochrome oxidase, and is resistant to the oxidant,
      plumbagin, under this condition, perhaps due to the high alternate oxidase. These
      phenotypes are similar to those of the mac1- mutant of Saccharomyces cerevisiae
      and the melanin-deficient grisea mutant of Podospora anserina, in which
      homologous transcriptional activators for the reductase and copper transporter
      genes are mutated. They constitute physiologic evidence that oxy2 is mutated in a
      homologous copper-related transcriptional activator of C. neoformans.

PMID- 15473358
TI  - Invasive fungal infections in Chile: a multicenter study of fungal prevalence and
      susceptibility during a 1-year period.
AB  - During the first year of an ongoing surveillance program of invasive fungal
      infections (IFI) a total of 130 patients (56% male) with fungal strains isolated
      from blood and other sterile sites were reported from 13 hospitals in Chile.
      Significant yeast isolates were obtained from 118 patients, and molds affected 12
      patients. The main patient groups affected were neonates, children less than 1
      year old and adults aged 50-79 years. All fungal bloodstream infections (BSI)
      were due to yeasts; 79 patients (61%) were affected. The main risk factors
      recorded were antibiotic therapy (76%), stay in the intensive care unit (ICU)
      (70%) and presence of a central venous catheter (65%). Nosocomial infections were
      represented in 83.5% of BSI. Overall, Candida albicans (40.8%), C. parapsilosis
      (13.1%), C. tropicalis (10%) and Cryptococcus neoformans (10%) were the most
      common species. Aspergillus fumigatus (3.1%) was the most frequent mold. C.
      albicans (48.1%) and C. parapsilosis (17.7%), were the most frequent agents
      recovered from blood. Saccharomyces cerevisiae and Trichosporon mucoides, two
      emerging pathogens, were also isolated. All yeasts tested were susceptible to
      amphotericin B with minimal inhibitory concentration (MIC) < or = 1 microg/ml.
      Resistance to itraconazole (MIC > or = 1 microg/ml) and fluconazole (MIC > or =
      64 microg/ml) was observed in 4 and 6% of cases, respectively. C. glabrata was
      the least susceptible species, with 50% of isolates resistant to itraconazole and
      33% resistant to fluconazole, with one strain showing combined resistance.
      Reduction of BSI requires greater adherence to hand-washing and related infection
      control guidelines.

PMID- 15473359
TI  - Apolipoprotein-E-deficient mice exhibit an increased susceptibility to
      disseminated candidiasis.
AB  - The effect of hyperlipoproteinemia on systemic candidiasis was investigated by
      assessing the susceptibility of hyperlipoproteinemic, apolipoprotein E (ApoE)
      deficient (ApoE -/-) mice to a systemic Candida albicans infection. The absence
      of ApoE in these mice resulted in an eightfold increase in plasma lipoprotein
      concentrations in the very low-density lipoprotein (VLDL) fraction, as compared
      with levels seen in ApoE +/+ mice. Mortality due to candidemia was significantly
      higher (86%) in ApoE -/- mice than in ApoE+/+ mice (52%), and in platings of
      homogenized kidney material on fungal culture medium, ApoE -/- mice yielded
      significantly higher levels of C. albicans outgrowth than did ApoE+/+ mice. C
      albicans grew twofold better in ApoE -/- plasma in 4 h than in ApoE+/+ plasma,
      and depletion of lipoproteins from plasma resulted in a significant seven- to
      tenfold increase in C. albicans growth. Recombinant ApoE did not directly inhibit
      C. albicans growth. Our data indicate that the increased susceptibility of ApoE 
      /- mice to C albicans is due both to increased growth of blastoconidia in ApoE -/
      mice in response to the availability of lipids as nutrients, and to the
      neutralization of candidacidal factors by lipoproteins. This study suggests that
      lipoproteins play a significant role in host defense against candidiasis.

PMID- 15473360
TI  - Separation of Paracoccidioides brasiliensis conidia through percoll gradients.
AB  - The conidia of Paracoccidioides brasiliensis are the structures most likely to
      serve as the infectious propagules of this fungus. This study describes our
      attempts to purify conidia by eliminating mycelial fragments. Purification was
      attempted using discontinuous 95% and 60% Percoll gradients with densities of
      1.167 and 1.107, respectively, prepared either in 0.15 mol/L PBS or 0.25 mol/L
      sucrose. The best results were observed with the 95% and 90% gradients in
      sucrose; with the former, conidial purity ranged from 70.6 to 100%, with a mean
      of 82.3% and a coefficient of variation (VC) of 11.7. With 90% gradients, purity
      was achieved between 70.4 and 92.5%. The mean in this case was 80.6% and the VC
      was 9.2%. The use of two consecutive 95% Percoll gradients in sucrose was tested.
      The recovery efficiency per plate, which averaged 2.5 x 10(6) conidia per plate
      with one gradient, increased to 5.1 +/- 1.3 x 10(6) conidia with two gradients.
      The use of Percoll did not affect the viability of the conidia, which was always
      > or = 90%. This method allows the preparation of a conidial sample almost free
      from contamination with mycelial fragments, thus facilitating quantitative
      determination of cause and effect in in-vivo interactions between P brasiliensis
      and its hosts.

PMID- 15473361
TI  - Cryptococcosis outbreak in psittacine birds in Brazil.
AB  - An outbreak of cryptococcosis occurred in a breeding aviary in Sao Paulo, Brazil.
      Seven psittacine birds (of species Charmosyna papou, Lorius lory, Trichoglossus
      goldiei, Psittacula krameri and Psittacus erithacus) died of disseminated
      cryptococcosis. Incoordination, progressive paralysis and difficulty in flying
      were seen in five birds, whereas superficial lesions coincident with respiratory
      alterations were seen in two birds. Encapsulated yeasts suggestive of
      Cryptococcus sp. were seen in faecal smears stained with India ink in two cases.
      Histological examination of the birds showed cryptococcal cells in various
      tissues, including the beak, choana, sinus, lungs, air sacs, heart, liver,
      spleen, kidneys, intestines and central nervous system. High titres of
      cryptococcal antigen were observed in the serum of an affected bird. In this
      case, titres increased during treatment and the bird eventually died. Yeasts were
      isolated from the nasal mass, faeces and liver of one bird. Cryptococcus
      neoformans var. gattii serovar B was identified based on biochemical,
      physiological and serological tests. These strains were resistant (minimum
      inhibitory concentration 64 microg/ml) to fluconazole. This is the first report
      of C. neoformans var. gattii occurring in psittacine birds in Brazil.

PMID- 15473362
TI  - IgM and IgG antibody response to Paracoccidioides brasiliensis in naturally
      infected wild armadillos (Dasypus novemcinctus).
AB  - We studied the extent to which wild nine-banded armadillos, Dasypus novemcinctus,
      produce immune humoral responses specifically directed against characteristic
      Paracoccidioides brasiliensis antigens. Such antibody production might reflect
      direct contact with the ecological microniche of P. brasiliensis, or might merely
      reflect inhalation of widely distributed airborne propagules. An enzyme-linked
      immunosorbent assay (ELISA) was designed containing purified glycoprotein gp43
      and gp70 antigens from P. brasiliensis as well as cross-reactive antisera
      originally targeted against human IgM (mu chain) and armadillo anti-IgG (gamma
      chain). It was used to detect and classify IgM and IgG antibodies to P.
      brasiliensis in the armadillo. In a serological survey of 47 wild armadillos, IgM
      antibodies to gp43 were detected in seven animals (14.8%), and IgG antibodies
      were detected in 20 (42.5%). IgM antibodies to gp70 were detected in 10 (21.3%)
      animals and IgG antibodies were detected in 18 (38.3%). These results, showing a
      pattern consistent with infection, suggest that P. brasiliensis is enzootic in
      armadillos. How the animals became exposed could not be determined.

PMID- 15473363
TI  - Chronic necrotizing pulmonary aspergillosis.
AB  - Chronic necrotizing pulmonary aspergillosis is not common and usually involves
      mildly immunosuppressed patients. We present a case of a 58-year-old man with a
      history of mining-related pneumoconiosis and corticosteroid therapy who developed
      bilateral pulmonary infiltrates and subsequent cavitation. The patient was
      treated at first as having community-acquired pneumonia and was only belatedly
      diagnosed as suffering from aspergillosis after Aspergillus fumigatus precipitins
      appeared in blood and the same fungus grew from bronchoalveolar lavage fluid. A
      transthoracic needle biopsy revealed fungal filaments present in material
      extracted from a pulmonary lesion that was visible on scans. Treatment with
      amphotericin B, begun at the time that aspergillosis was diagnosed, proved to be
      ineffective, as was a later change to amphotericin B lipid complex. The diagnosis
      was confirmed at necropsy.

PMID- 15473364
TI  - Wound infection due to Absidia corymbifera and Candida albicans with fatal
      outcome.
AB  - A case of a mixed infection due to Candida albicans and the zygomycete Absidia
      corymbifera in a 38-year-old, previously healthy, Caucasian male is presented.
      The infection developed following serial rib fractures, and ruptures of kidney,
      liver and biliary tract as well as a pancreatic contusion resulting from a
      traffic accident. During intensive care treatment the patient underwent several
      surgical procedures but subsequently experienced multi-organ failure and sepsis.
      Some weeks later, fungal growth was observed macroscopically on the patient's
      skin and wounds. From wound swabs C. albicans and A. corymbifera were grown.
      Histopathology of abdominal tissue yielded pseudohyphae and coenocytic hyphae.
      Although surgical debridement and antifungal treatment with amphotericin B and 5
      flucytosine were started immediately, the patient died in therapy-refractory
      septic multi-organ failure.

PMID- 15473365
TI  - Canine paracoccidioidomycosis.
AB  - Paracoccidioidomycosis (PCM) is a severe disease caused by the dimorphic fungus
      Paracoccidioides brasiliensis, which is characterized by granulomatous pulmonary
      and systemic lesions, affecting mainly men between 20 and 60 years of age.
      Reports of PCM disease in animals are rare, but the disease has been described in
      armadillos. On the other hand, PCM infection of domestic and wild animals
      detected by serological or cutaneous tests in the absence of apparent disease has
      been frequently reported. We present here the case of a female adult Doberman
      that developed cervical lymphadenomegaly. Histopathological examination of a
      cervical biopsy specimen revealed active PCM, with an epithelioid, granulomatous
      inflammation containing numerous yeast-like, multiple budding fungal forms. The
      diagnosis of PCM was confirmed by immunohistochemistry using a specific antibody
      anti-gp43 and by nested PCR using primers for the amplification of the gp43 gene
      region. This is the first report of PCM disease occurring in a dog, an animal
      that has been shown to play an important role in the natural history of North
      American blastomycosis.

PMID- 15473366
TI  - Ergosterol gene expression in wild-type and ergosterol-deficient mutants of
      Candida albicans.
AB  - The ergosterol pathway is the major target of the azole antifungals. We have
      developed a panel of five viable ergosterol biosynthetic mutants (erg2, erg3,
      erg6, erg11 and erg24) and have performed Northern analyses to study
      transcriptional regulation using probes to four ergosterol biosynthetic genes
      (ERG2, ERG7, ERG11 and ERG25), as well as probes to two additional genes encoding
      ergosterol cytochrome coenzymes (CYB5 and NCP1). ERG11, which encodes the sterol
      14-demethylase, the direct target of the azole antifungals, was the most up
      regulated gene followed by ERG7 and ERG25. Transcription of the four ergosterol
      genes was most up-regulated in erg24 and erg6 mutant backgrounds, deficient in C
      14 reductase and the C-24 sterol transmethylase, respectively. Unexpectedly, we
      also found that the two cytochrome genes, CYB5 encoding cytochrome b5 and NCP1
      encoding the cytochrome P450 reductase, were not regulated markedly different
      from wild-type in the erg2, erg3, erg6, erg11 and erg24 strains of Candida
      albicans.

PMID- 15473367
TI  - Agrobacterium tumefaciens-mediated transformation of Paracoccidioides
      brasiliensis.
AB  - Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis,
      an important mycosis endemic to Latin America. As the tools to study gene
      function in P. brasiliensis are only in the early stage of development, there is
      presently no system that allows for both the delivery and integration of
      exogenous nucleic acids into its genome. We report in this paper the
      transformation of the yeast phase of P. brasiliensis (ATCC-60855) with
      Agrobacterium tumefaciens (GV3101) carrying the vector pAD1625. The
      microorganisms were co-cultivated for 2 days and then incubated for 10 days at 35
      degrees C on selective media. PCR and dot-blot targeted at a fragment of 222 bp
      from the hph (hygromycin phosphotransferase) gene which confers Hygr confirmed
      the transformation of P. brasiliensis.

PMID- 15473368
TI  - [Consolidation of cytoskeleton during plant spindle formation. I. Abnormalities
      of spindle integrity in meiosis].
AB  - The process of formation of multiple spindles in mononucleate pollen mother cells
      during meiosis in general wide hybrids F1 and haploids is described. It is
      assumed that the abnormality may be caused by aberration of a special process at
      late prometaphase providing for the spindle consolidation.

PMID- 15473369
TI  - [Structural and functional characterization of cyst cells in Sarcocystis sp.
      (Sporozoa, Apicomplexa)].
AB  - By means of light and electron microscopy, the structural pattern of muscle cysts
      (sarcocysts) was examined for the four species of the genus Sarcocystis: S. muris
      (from murine skeletal muscles), Sarcocystis sp. and S. fusiformis (from,
      respectively, heart and skeletal muscles of buffalo), and S. ovifelis (from ovine
      tong muscles). The orderly fashion of the interior of the cyst is attained by
      partitition of its space into numerous compartments with the involvement of the
      intermediate filaments. These, in their turn, are bound to each other by thin
      filaments to make eventually a common filamentous net. The net limits separate
      groups of cells referred to as cyst zoites. The common net of filaments and
      microtubules (when present) may be regarded not only as the organizer of the cyst
      interior cytoskeleton, but also as the main mechanism of substance transportation
      in various directions: from the host cell to the sarcocyst, and within or outside
      the cyst. The role of dedifferentiation, proliferation and differentiation
      processes is suggested in the establishment of the fixed sequence of events
      throughout the unidirectional development of cyst cells and their interaction,
      from precystic meronts to cyst merozoites (gamonts). Special attention is paid to
      metrocyte morphogenesis and functioning. In the present work, metrocytes
      subjected to apoptosis were recognized. It is suggested that phenomenon of
      programmed cell death in metrocytes may be associated with the control of cell
      number in mature and ageing sarcocysts.

PMID- 15473370
TI  - [Effect of synthetic proteasomal inhibitor MG132 on dynamics of EGF-receptor
      complexes endocytosis in A431 cells].
AB  - The effect of proteasomal activity suppression induced by MG132, a synthetic
      proteasomal inhibitor of EGF-receptor complexes endocytosis in human epidermoid
      carcinoma A431 cell line, was studied. Using subcellular fractionation in 17%
      Percoll gradient, it was demonstrated that the addition of MG132 to the cells 15
      min following stimulation of EGF endocytosis resulted in a slight accumulation of
      125I-EGF in early endosomes, and in much more significant accumulation of the
      labeled growth factor in late endosomes/lysosomes, as compared to untreated
      cells. The release of 125I-EGF degradation products into the incubation medium
      was significantly (3-12-fold) inhibited in the presence of MG132. At the same
      time biochemical analysis has demonstrated that the EGF receptor itself is not a
      direct target of proteasomes, since it is revealed as a full-length protein with
      native mol. mass (170 kDa) in fractions of early and late endosomes and
      lysosomes. Possible mechanisms of the MG132 effect on intracellular processing of
      EGF-receptor complexes are discussed.

PMID- 15473371
TI  - [Cell shrinkage during apoptosis is not obligatory. Apoptosis of U937 cells
      induced by staurosporine and etoposide].
AB  - A study was made of apoptotic cell shrinkage, which is generally believed to be a
      hallmark of apoptosis. The two conventional models of apoptosis were used for
      examination of changes in cell water balance--one is apoptosis caused in human
      lymphoma cell line U937 by staurosporine, and the other by etoposide.
      Intracellular water was determined by measuring buoyant density of cells in
      continuous Percoll gradient. Apoptosis was recognized by microscopy and flow
      cytometry. Apoptosis caused by staurosporine (1 microM, 4 h) was found to be
      associated with a decrease in cell water content by almost 24%. In contrast, no
      decrease in cell water content was observed in U937 cells incubated with
      etoposide (50 microM, 4 h), in spite of the number of features suggesting the
      presence of apoptosis, such as the appearance of apoptotic bodies, chromatin
      condensation and fragmentation and disappearance of S-phase cells in DNA
      histogram. It is concluded that definition of apoptosis as "shrinkage-necrosis"
      (Kerr, 1971) needs correcting: the distinction of apoptotic cells involves the
      absence of swelling, rather than cell shrinkage.

PMID- 15473372
TI  - [Dynamics of chaperone complex Hdj1-Hsp70-Bag1 as a response of erythroleukemia
      K562 cells to heat stress].
AB  - Heat shock protein Hsp70 is known to play an important role in cell protection
      against a variety of harmful factors. This property, at least in part, is due to
      Hsp70 ability to restore the native conformation of newly synthetized or damaged
      proteins. In this activity Hsp70 is accompanied by two proteins, Hdj1 and Bag1,
      that enable Hsp70 to peform cycles of binding-release of target proteins. The aim
      of this study was to investigate interactions of Hdj1 and Bag1 co-chaperones with
      Hsp70 in vivo. The accumulation of Hsp70 was stimulated by heat stress, and
      later, at certain periods following the stress, cell probes were collected for
      biochemical and microscopic analysis. The data of Western blotting showed that
      within 24 h after heat shock amounts of Hsp70 and Hdj1 raised to remain at the
      elevated level for nearly 48 h. Several time points within this period were
      chosen for analysis of the complexes between Hsp70 and co-chaperones. The data of
      reciprocal immunoprecipitation/immunoblotting and confocal microscopy showed that
      Hsp70-Hdj1 complexes were detected primarily at early stage after heat shock,
      then Hsp70 was preferably bound to Bag1. The dynamics of chaperone complex
      formation and changes in their intracellular localization are discussed in terms
      of cell reaction to stress.

PMID- 15473373
TI  - [Interaction between filamentous actin and lipid bilayer causes the increase of
      syringomycin E channel-forming activity].
AB  - The effect of filamentous (F) actin on the channel-forming activity of
      syringomycin E (SRE) in negatively charged and uncharged bilayer lipid membranes
      (BLM) was studied. F-actin did not affect the membrane conductance in the absence
      of SRE. No changes in SRE-induced membrane conductance were observed when the
      above agents were added to the same side of BLM. However, the opposite side
      addition of F-actin and SRE provokes a multiple increase in membrane conductance.
      The similar voltage dependence of membrane conductance, equal values of single
      channel conductance and the effective gating charge of the channels upon F-actin
      action suggests that the actin-dependent increase in BLM conductance may result
      from an increase in the number of opened SRE-channels. BLM conductance kinetics
      depends on the sequence of SRE and F-actin addition, suggesting that actin
      dependent rise of conductance may be induced by BLM structural changes that
      follow F-actin adsorption. F-actin exerted similar effect on membrane conductance
      of both negatively charged and uncharged bilayers, as well as on conductance of
      BLM with high ionic strength bathing solution, suggesting the major role for
      hydrophobic interactions in F-actin adsorption on lipid bilayer.

PMID- 15473374
TI  - [Distribution of satellite DNA TkS1 in genomes of salamanders (Salamandridae)].
AB  - Genomes of 22 species and subspecies of salamandrids (Triturus, Cynops,
      Neurergus, Notophthalmus, Pachytriton, and Pleurodeles ) were studied. Satellite
      TkS1 (32-33 bp) was found in all examined species, both in direct and reversed
      orientations. The use of single-primer PCR with oligonucleotides, which are
      homologous to the most conservative part of satellite TkS1, allowed us to reveal
      DNA fragments, flanked by single copies (or small tandem repeats) of satellites
      TkS1 having various (5' and 3') orientation. Such fragments were observed in
      Pleurodeles waltl, Triturus a. alpestris, T. vulgaris lantzi, T. v. vulgaris,
      Neurergus crocatus and T. vulgaris graecus. The length of amplified DNA fragments
      in three subspecies of T. vulgaris differed. This might be connected with unequal
      amounts and different distribution of 5' and 3' copies of satellite TkS1 in their
      genomes. Patterns of DNA amplification in Triturus a. alpestris and Neurergus
      crocatus were quite similar. Only two species (Triturus a. alpestris and T. v.
      vulgaris) had approximately equal amounts and similar distribution of 5' and 3'
      copies of satellite TkS1 in their genomes.

PMID- 15473375
TI  - Genome multiplication of extravillous trophoblast cells in human placenta in the
      course of differentiation and invasion into endometrium and myometrium. II.
      Mechanisms of polyploidization.
AB  - Peculiarities of the structure of interphase nuclei, mitotic activity, and Ki-67
      protein intranuclear immunolocalization were studied to elucidate mechanisms of
      genome multiplication in proliferative and differentiating invasive extravillous
      trophoblast cells in the human placenta. The presence of numerous chromocenters
      was shown to be a characteristic feature of proliferative cell nuclei of both
      villous and extravillous trophoblast. At the beginning of extravillous
      trophoblast cell differentiation, i.e. in the proximal part of cell columns, some
      amount of cells with large nuclei containing enlarged chromocenters were found.
      DNA content was measured simultaneously with counting the number of chromocenters
      in similarly looking nuclei of squash preparations of placental villi. The
      increase in the ploidy level up to 4c-8c, accompanied by a slight increase in the
      number of chromocenters being not proportional to the ploidy level and not
      exceeding the diploid number of chromosomes of the human genome, was
      demonstrated. This suggests that genome multiplication of extravillous
      trophoblast cells may be accomplished by endoreduplication. In addition, pictures
      of endomitosis were seen at early steps of differentiation of EVT cells. The lack
      of polyploid mitotic figures or any obvious polyploidizing or restitutional
      mitoses suggests that these are not of considerable importance in genome
      multiplication of human EVT cells. However, the prevalence of metaphases at the
      boundary of the distal part of cell columns suggests that restitutional mitoses
      may be involved, even partly, in human trophoblast cell polyploidization. At
      later steps of differentiation, i.e. in the distal part of cell columns, the
      nuclear structure obviously changes, with a uniform "network" chromatin
      arrangement prevailing, whereas numerous chromocenters and features of
      endomitosis are no longer seen. The pattern of Ki-67 protein immunolocalization
      is also changing along the invasive pathway. In the proliferating stem cells and
      trophoblast cells of the proximal part of cell columns, Ki-67 was localized in
      the karyoplasm, chromocenters and numerous small nucleoli, whereas in the distal
      part of cell columns this protein was detected predominantly in 1-2 large
      nucleoli. The comparative analysis of the literature data on Ki-67 localization
      at different stages of cell cycle provided another evidence that EVT cells in the
      course of invasion may switch to the endoreduplication cycle. In agreement with
      the relevant report on rodent placentation, our present data suggest that
      acquirement of an invasive phenotype of EVT cells is accompanied by switching
      from mitotic division to endoreduplication cycle.

PMID- 15473376
TI  - [Cytogenetical approaches to the problem of form-formation and subspeciation in
      the complex Lacerta (Zootoca) vivipara (Lacertidae, Sauria)].
AB  - Results of the author's long-term study of the karyotype of Lacerta (Zootoca)
      vivipara (family Lacertidae, Sauria) have been generalized and supplemented with
      relevant literature data. Within the species an interpopular karyotype
      variability was established, and several chromosomal forms were described.
      Karyotypes of L. (Z.) vivipara from four new, previously not examined populations
      have been first presented in this paper, and cytogenetical features of their
      chromosomes are given. Finally, cytogenetical analysis of particular specimens
      from different localities enabled the author to reveal a new chromosomal form and
      to define the limits of distribution of other forms of the species. The complex
      L. (Z.) vivipara has appeared to be more complicated than earlier believed. This
      complex includes several chromosomal forms of unclear taxonomic status, and some
      subspecies characterized by various modes of reproduction and distinct
      distribution ranges. It has been confirmed that in the complex L. (Z.) vivipara
      intensive chromosomal changes accompany the processes of form-formation and
      subspeciation. Some cytogenetical regularities of these processes have been
      demonstrated and compared with hybridogeneous form-formation and speciation.
      Based on the critical analysis of the available karyological data, some
      mechanisms of chromosomal changes were described, and their tendencies were
      determined. In addition, intraspecific relationships were analysed. The proposed
      scheme was compared with the pattern of intraspecific phylogeny of L. (Z.)
      vivipara based on molecular data. It has been shown that a high cytogenetical
      differentiation of the found chromosomal forms and subspecies is correlated with
      their low morphological differentiation and with a rather low genetical
      differentiation. The results of the combined analysis suggest the leading role of
      cytogenetical data for understanding the processes of form-formation and
      subspeciation. The importance of chromosomal rearrangements in these processes is
      emphasized, with special reference to their role in the evolution and phylogeny
      of the complex L. (Z.) vivipara. Some modes of form-formation and subspeciation
      in this complex are discussed.

PMID- 15473377
TI  - [Mating types in the ciliate Dileptus anser. Shortening of maturation period
      after micrurgical bisection of exconjugant cells].
AB  - In many ciliates, young exconjugant clones demonstrate sexual immaturity: they
      are not able to conjugate with mature cells of complementary mating types (MTs).
      After several scores of cell divisions, a short period of adolescence (partial
      maturity) commonly occurs followed by maturation, after which these cells are
      able to conjugate with cells of other, i.e. complementary, MTs again. Tavrovskaja
      (1981) reported a significant reduction in the maturity period in Dileptus anser
      clones, grown from exconjugant ciliates regenerated from small cell fragments. To
      verify this, in the present study exconjugant D. anser cells were bisected with
      glass needle after 3 to 4 cell divisions following conjugation. The same
      procedure was performed with survived and regenerated cells on the 2nd and 3rd
      days. The clones thus obtained were cultivated, and their ability to mate with
      each of the three standard clones of MT I, II and III was tested week by week.
      Indeed, in 22 F1 clones from cross N 7C (MT I) x N 2 (MT II) the immaturity
      period was reduced 1.4-3.4-fold (2.18 in average) after a threefold bisection, as
      compared with that in intact subclones. Similarly, in 27 F1 clones from cross N
      20 (MT I) x N 14 (MT II) this period was shortened 1.6-3.0-fold (2.19 in
      average). 12 of these clones showed a 0.9-2.4-fold (1.53 in average) reduction
      after a single bisection, and 1.6-2.8 (2.12 in average) after a threefold
      operation. Thus, micrurgical fragmentation of young exconjugant cells can be used
      to accelerate maturation in D. anser.

PMID- 15473378
TI  - [Tick-borne infections].
AB  - Ticks are obligate, blood-sucking ectoparasites that are the most common agents
      of vector-borne infectious disease in the United States and European countries.
      Ticks play an important role in transmitting several infectious agents, such as
      viruses, bacteria, spirochetes, rickettsia, and parasites, and tick bites cause a
      variety of acute and chronic infectious diseases, including Lyme disease, tick
      borne relapsing fever, Rocky Mountain and Mediterranean spotted fevers,
      ehrlichiosis, Q fever, tularemia, babesiosis, and tick-borne viral encephalitis.
      Since its identification nearly 30 years ago, Lyme disease has continued to
      spread, and it is now the most commonly reported arthropod-borne illness in
      American and European countries. Rickettsial infections are widely distributed
      throughout the world and have a remarkable influence on public health and
      military activities as a possible biological weapon. Tick-borne encephalitis
      virus is endemic in central, eastern and northern Europe and may cause a wide
      spectrum of clinical forms, ranging from asymptomatic infection to severe meningo
      encephalitis. This article reviews the epidemiology, microbiology, clinical
      manifestation, diagnosis and treatment of the major tick-borne infectious
      diseases in the United States and Europe.

PMID- 15473379
TI  - [No floroquinolone resistance in non typhoidal salmonellas from hospitalized
      persons in an endemic area of Apulia, Italy].
AB  - Non typhi-salmonella is the most common cause of hospitalization or death
      associated with acute diarrhea. It is usually a self limiting disease and
      antibiotic therapy is not required, but in immunocompromised people it is
      essential. Increasing antimicrobial resistance in salmonella, in future, would
      limit the therapeutic options. During 2002, 198 persons were hospitalized for
      acute gastroenteritis. The 55% of cases were female, the age ranged between 4 and
      94 years and the 25% of them were > 60 years old. The 58.5% of hospitalizations
      occurred between June and October. Non-typhi salmonella was isolated in the stool
      of 49 persons, with a rate of hospitalization of 24.7% respect to other causes of
      gastroenteritis. The incidence of resistance that was defined as resistance to
      one or more drugs was 14.3%. Only one non-typhi salmonella showed a multiple
      resistance (> four drugs). Among all antibiotics tested, only the fluorquinolones
      showed a susceptibility in vitro in all strains. Non typhoidal Salmonellosis is a
      public healt problem in the world and it will be important to restrict the use of
      antibiotics in medicine and veterinary to reduce the spread of multiresistant
      strains.

PMID- 15473380
TI  - [Freezing of gait is a symptom of Parkinson disease].
AB  - One could distinguish between "off freezing", which is a symptom tightly bound to
      L-dopa dosage and titration, and is clinically bound to wearing off, and, on the
      contrary, "on freezing" which does not respond to therapy modifications or to
      different drug's titration. On freezing seems to be related to frontal-basal
      ganglia-pontine neural pathway disruption. This neural disruption may be related
      with altered perception of extra and peri-personal space which are two major
      problems of these patients. We demonstrate in a group of patients with "on
      freezing" evident defect of attention, focus capability, of set-shifting
      properties, and of alteration in body/space relationship. We discuss on results
      obtained by specific training of physiotherapy with an review on literature.

PMID- 15473381
TI  - [Multiple bilateral chondromatous hamartomas of the lung. A rare entity mimicking
      carcinoma].
AB  - Multiple chondromatous hamartomas of the lung are extremely rare. We report a
      case of a 78 year-old man admitted to our service for a neurological syndrome
      associated with cerebral cancer. Chest-X-ray and computed tomography revealed
      multiple and bilateral pulmonary nodules. A metastatic carcinoma was initially
      taken into account but, in the light of natural history of the disease, clinical
      examination and CT-scan characteristics of the lesions, we formulated the final
      diagnosis of multiple bilateral chondromatous hamartomas of the lung.

PMID- 15473382
TI  - [Arthritides in the elderly].
AB  - The arthritides of the elderly comprise a fairly heterogeneous group of diseases.
      They include conditions that affect exclusively or predominantly the elderly
      (such as, for instance, remitting seronegative symmetric synovitis with pitting
      edema) and conditions affecting any age group, but which can present with
      peculiar features in the elderly, like rheumatoid arthritis and the seronegative
      arthropathies. Therefore, in order to arrive at a correct diagnosis, a knowledge
      of the specific features of these disorders is required. In addition, the
      treatment of elderly patients differs from that of other age groups in that
      elderly subjects appear to have an increased susceptibility to adverse reactions.
      This susceptibility is related both to the different metabolism of aged subjects,
      including the impairment of the renal function, and to the multiple therapies
      that such subjects often receive. In view of the ever increasing elderly
      population in the western world, all physicians, over and beyond the limited
      circle of rheumatologists, should be knowlegeable about the principles of
      diagnosing and treating senile arthritis.

PMID- 15473383
TI  - [Thyroid dysfunction and pulmonary hypertension].
AB  - Prior observational studies and several case reports have suggested an
      association between thyroid dysfunction and pulmonary hypertension. This review
      was designed to evaluate the prevalence and the pattern of pulmonary vasculature
      involvement in hyper- and hypothyroidism. We identified original research papers
      and reviews by going through leading journals that publish basic and clinical
      research in the fields of pulmonary hypertension, hyperthyroidism and
      hypothyroidism, by electronically searching the Medline database. We directed
      special attention to papers published from 1972 to 2003. Our findings indicate
      the presence of a frequent association between hyperthyroidism and pulmonary
      hypertension (35% in the largest series of cases) which decrease after
      achievement of a euthyroid state. A possible explanation includes an influence of
      thyroid hormones which affect growth and maturation of vascular cells and
      enhanced catecholamine sensitivity causing pulmonary vasoconstriction.
      Furthermore, several studies suggest a high prevalence of transient pulmonary
      hypertension in hypothyroidism (49% in the largest series of cases), in these
      cases autoimmunity play a key role.

PMID- 15473384
TI  - [The bird on the head of the hippopotamus].

PMID- 15473385
TI  - [Reference values in oral health-related quality of life for the abbreviated
      version of the Oral Health Impact Profile].
AB  - Questionnaires measuring oral health-related quality of life (OHRQoL) need
      reference values for their interpretation. Population-based norms for a
      questionnaire allow a comparison of the level of OHRQoL observed for an
      individual or a group of subjects with the level of that construct in the general
      population. The aims of this study were to establish normative values for
      abbreviated instruments of the German version of the Oral Health Impact Profile
      (OHIP-G). Data of the long OHIP-G (53 items) were collected in a national survey
      (N=2050, age: 16-79 years). Three short instruments with 5 (OHIP-G5), 14 (OHIP
      G14) and 21 items (OHIP-G21) were derived from the long OHIP. Norms were computed
      for the OHIP-G summary score (simple sum of all item responses). The OHIP-G
      summary score distribution was described by empirical cumulative distribution
      functions. Because denture usage was strongly associated with OHIP-G summary
      scores, percentile-based norms were stratified by this variable. Among subjects
      without dentures, 50% of the population had OHIP-G5 or OHIP-G14 scores 0 and OHIP
      G21 scores < or = 2. Summary scores for the three abbreviated OHIPs were < or =
      2, < or = 4, and < or = 7 for subjects with removable dentures and < or = 3, < or
      = 6, and < or = 8 for subjects with complete dentures. Among subjects without
      dentures, 90% of the population had < or = 4 OHIP-G5, < or = 11 OHIP-G14, and <
      or = 16 OHIP-G21 points. For subjects with removable dentures, the figures were <
      or = 7, < or = 17, and < or = 26 points for OHIP-G5, OHIP-G14 and OHIP-G21,
      respectively; and for subjects with complete dentures, < or = 10, < or = 25, and
      < or = 38 points, respectively. The presented norms will provide a frame of
      reference in future cross-sectional studies in the general population or samples
      with specific oral conditions when OHRQoL is measured by OHIP-G5, OHIP-G14 or
      OHIP-G21.

PMID- 15473386
TI  - [Influence of the implant surface on the early phase of osteogenesis in vitro].
AB  - The specific structure of a dental implant's surface is often used as an argument
      for a better overall performance and durability. Nonetheless, it is not yet fully
      clear to what extent an implant's material or surface structure improves its
      performance. For a better understanding of the early integration-related
      processes, growth and initiation of mineralization of human MG-63 osteoblasts
      grown on glass slides or on polished (MS: machine-surfaced) or structured (SB:
      deep-structured) titanium surfaces were monitored. Cells were cultured under non
      confluent conditions in absence and presence of osteogenic medium (OS). The 3D
      architecture of growing cells was documented by confocal laser scanning
      microscopy (CLSM) upon fluorescently labeling for collagen I. Collagen I
      distribution was found comparable under all conditions. In control cultures on
      glass, MS and SB, cells had grown as multilayered but not yet confluent networks,
      which additionally comprised dome-like structures on the two Ti-surfaces. While
      on glass and SB cells essentially maintained this architecture also in presence
      of OS, three-dimensional structures on MS were--if at all--only barely visible.
      This was reflected also in the protein content of the cultures that was
      significantly lower under OS in the case of MS only. The activity of the early
      mineralization marker alkaline phosphatase (ALP) was higher in the controls on
      glass than on MS or SB. In presence of OS it was significantly higher on MS and
      SB than in the controls, yet not on glass. Obviously both, the surface material
      and the surface structure contribute--possibly synergistically--to early
      processes of implant integration, such as matrix formation and mineralization.
      The impact of such effects is discussed, in relation to implant loading and
      implant durability.

PMID- 15473387
TI  - [Effect of orthodontic tooth intrusion on the periodontium. Clinical study of
      changes in attachment level and probing depth at intruded incisors ].
AB  - The goal of the present study was to measure attachmentlevel changes in patients
      of 12-48 years of age whose maxillary incisors have been intruded during an
      orthodontic treatment lasting between 9 and 14 months. Clinical parameters such
      as clinical probing depth, clinical attachment level and bleeding on probing were
      evaluated. The results show that i) the intruded teeth gained an average of 0.6
      mm of clinical attachment, while the control teeth showed a stable attachment
      level and ii) the clinical probing depth remained stable at test and control
      teeth. It was concluded that orthodontical intrusion of maxillary front teeth in
      patients with a high level of oral hygiene maintains stable periodontal
      parameters and may even lead to a small clinical attachment gain.

PMID- 15473388
TI  - Teaching towards normal birth.

PMID- 15473389
TI  - Baby dies in transfer from midwife-led unit (TPM, 7:7, 10).

PMID- 15473390
TI  - TTP and me.

PMID- 15473391
TI  - The assisted conception pregnancy.

PMID- 15473392
TI  - Safe motherhood--checking for anaemia.

PMID- 15473393
TI  - 'Personhood' and the right to life.

PMID- 15473394
TI  - The baby's friend.

PMID- 15473395
TI  - Air or oxygen? Resuscitation of infants at birth.

PMID- 15473396
TI  - Disability and reproduction.

PMID- 15473397
TI  - Research: the hidden stories.

PMID- 15473398
TI  - Fathers Direct: Working With Fathers. 5 April, London.

PMID- 15473399
TI  - Normal Labour and Birth: 2nd Research Conference. 9-11 June, Lake District.

PMID- 15473400
TI  - A family affair.

PMID- 15473401
TI  - Ferid Murad--1998 Nobel laureate for nitric oxide research.

PMID- 15473402
TI  - Electron beam computed tomography: the latest "stethoscope" for calcific aortic
      valve disease.

PMID- 15473403
TI  - Association of cardiovascular risk factors to aortic valve calcification as
      quantified by electron beam computed tomography.
AB  - OBJECTIVE: To analyze the association among aortic valve calcification,
      cardiovascular risk factors, and coronary artery calcification using electron
      beam computed tomography (EBCT). PATIENTS AND METHODS: We analyzed cardiac EBCT
      data obtained for coronary calcium detection in 1000 consecutively enrolled
      patients (mean +/- SD age, 57.1 +/- 10 years; 69% men) between January 1, 1998,
      and July 23, 2001. In all patients, atherosclerotic risk factors (hyperlipidemia,
      hypertension, diabetes, smoking, and family history of coronary artery disease)
      were documented. With EBCT, the amount of coronary calcification was determined
      using the Agatston score, and the amount of aortic valve calcification was
      measured using a volumetric score. RESULTS: Aortic valve calcification was
      detected in 177 (17.7%) of the total patient group and was found more frequently
      in patients with coronary calcification (20.5% in patients with coronary calcium
      vs 3.8% in patients without coronary calcium; P < .001), hyperlipidemia (19.5% vs
      6.5%; P < .001), hypertension (21.7% vs 13.9%; P = .01), or diabetes (30.7% vs
      16.6%; P = .002). The volume of aortic valve calcification was significantly
      higher in patients with vs without hyperlipidemia (P < .001), hypertension (P =
      .002), and diabetes (P = .001). In a multivariable logistic regression analysis,
      adjusted for age and sex, hyperlipidemia (P = .001) and the presence of coronary
      calcification (P < .001) were significant predictors of aortic valve
      calcification. CONCLUSION: A significant association exists among atherosclerotic
      risk factors, coronary calcification, and the presence and amount of aortic valve
      calcification.

PMID- 15473404
TI  - Pilot evaluation of paroxetine for treating hot flashes in men.
AB  - OBJECTIVE: To provide prospective information on the potential utility of
      paroxetine for treating hot flashes In men receiving androgen ablation therapy
      for prostate cancer. PATIENTS AND METHODS: Men with symptomatic androgen ablation
      therapy-related hot flashes were entered into this clinical trial between August
      2001 and October 2003. After a baseline week of documentation of the frequency of
      hot flashes, patients were assigned to receive paroxetine; the initial dosage was
      12.5 mg/d, and it was increased to 37.5 mg/d over the ensuing 4 weeks. RESULTS:
      Of the 24 patients in whom medication was initiated, 18 completed the 5-week
      study. In these patients, the median frequency of hot flashes decreased from 6.2
      per day during the baseline week to 2.5 per day during the last study week. Hot
      flash scores (frequency x mean severity) during the same period decreased from
      10.6 per day to 3.0 per day. Overall, paroxetine was well tolerated by most
      patients. CONCLUSION: The results from this trial suggest that paroxetine Is an
      effective agent for diminishing hot flashes in men receiving androgen ablation
      therapy.

PMID- 15473405
TI  - Association of painless acute aortic dissection with increased mortality.
AB  - OBJECTIVE: To evaluate the clinical characteristics and outcomes of patients with
      painless acute aortic dissection (AAD). PATIENTS AND METHODS: For this study
      conducted from 1997 to 2001, we searched the International Registry of Acute
      Aortic Dissection to identify patients with painless AAD (group 1). Their
      clinical features and in-hospital events were compared with patients who had
      painful AAD (group 2). RESULTS: Of the 977 patients in the database, 63 (6.4%)
      had painless AAD, and 914 (93.6%) had painful AAD. Patients in group 1 were older
      than those in group 2 (mean +/- SD age, 66.6 +/- 13.3 vs 61.9 +/- 14.1 years; P =
      .01). Type A dissection (involving the ascendIng aorta or the arch) was more
      frequent in group 1 (74.6% vs 60.9%; P = .03). Syncope (33.9% vs 11.7%; P <
      .001), congestive heart failure (19.7% vs 3.9%; P < .001), and stroke (11.3% vs
      4.7%; P = .03) were more frequent presenting signs in group 1. Diabetes (10.2% vs
      4.0%; P = .04), aortic aneurysm (29.5% vs 13.1%; P < .001), and prior
      cardiovascular surgery (48.1% vs 19.7%; P < .001) were also more common in group
      1. In-hospital mortality was higher in group 1 (33.3% vs 23.2%; P = .05),
      especially due to type B dissection (limited to the descending aorta) (43.8% vs
      10.4%; P < .001), and the prevalence of aortic rupture was higher among patients
      with type B dissection in group 1 (18.8% vs 5.9%; P = .04). CONCLUSION: Patients
      with painless AAD had syncope, congestive heart failure, or stroke. Compared with
      patients who have painful AAD, patients who have painless AAD have higher
      mortality, especially when AAD is type B.

PMID- 15473406
TI  - Lack of association between lipoprotein(a) and coronary artery calcification in
      the Genetic Epidemiology Network of Arteriopathy (GENOA) study.
AB  - OBJECTIVE: To investigate the relationship between lipoprotein(a) [Lp(a)] levels
      and the extent of coronary atherosclerosis in a cohort that consisted
      predominantly of hypertensive patients. PATIENTS AND METHODS: Patients were
      ascertained through sibships that contained at least 2 individuals with essential
      hypertension diagnosed before the age of 60 years. The 10-year coronary heart
      disease (CHD) risk was estimated on the basis of the Framingham risk equation.
      Serum Lp(a) was measured by an immunoturbidimetric assay. Coronary artery
      calcification (CAC) was measured noninvasively by electron beam computed
      tomography and CAC score calculated using the Agatston score. RESULTS: Patients
      included 765 non-Hispanic, white individuals (59% women) participating in the
      Genetic Epidemiology Network of Arteriopathy study. The mean +/- SD age of the
      patients was 62 +/- 8 years, and 77% had hypertension. The prevalence of
      detectable CAC was 87% in men and 60% in women. The CAC scores did not differ
      significantly across quintiles of Lp(a) levels in either men or women. In a
      multiple regression model that included conventional risk factors, Lp(a) levels
      were not related to CAC quantity in either sex. No significant interactions were
      noted between Lp(a) levels and the conventional risk factors in the prediction of
      CAC quantity. When stratified on the basis of the 10-year CHD risk, 26.5% of the
      patients were low risk (< 6%), 60.5% were intermediate risk (6%-20%), and 12.9%
      were high risk (> 20%). Lipoprotein(a) was not associated with CAC quantity
      within subgroups based on 10-year CHD risk. CONCLUSION: In this cohort enriched
      with hypertensive patients, the estimated 10-year CHD risk did not appear to
      modify the lack of an association between Lp(a) levels and CAC.

PMID- 15473407
TI  - Complications of endoscopy of the upper gastrointestinal tract: a single-center
      experience.
AB  - OBJECTIVE: To evaluate prospectively the complications that occurred during
      consecutive endoscopies of the upper gastrointestinal tract. PATIENTS AND
      METHODS: We evaluated all endoscopies of the upper gastrointestinal tract (except
      endoscopic retrograde cholangiopancreatography and endosonography) performed at
      the Ambulatory Surgical Center at the Mayo Clinic in Jacksonville, Fla, between
      January 1999 and June 2002. A staff gastroenterologist with or without a trainee
      performed these procedures. Therapeutic procedures included esophageal band
      ligation, injection sclerotherapy, botulinum toxin injection, extended upper
      endoscopy, pneumatic balloon dilation, endoscopic mucosal resection, and
      endoscopic ablation using thermal laser, argon beam coagulator, or photodynamic
      therapy. All complications were tabulated prospectively as per mandatory state
      licensure reporting. RESULTS: Complications after diagnostic endoscopy of the
      upper gastrointestinal tract were related to anesthesia in 2 of the 12,841
      patients. Perforations in 5 patients were associated with esophageal dilation
      (2), resection of duodenal lesions (2), or passage of a side-viewing instrument
      into the duodenum (1). No deaths occurred. CONCLUSIONS: Diagnostic endoscopy of
      the upper gastrointestinal tract is safe, with a complication rate of less than 1
      per 5000 cases. Therapeutic endoscopy increases the risk of complications.
      Compared with complication rates published previously, our results from a single
      center indicate a favorable reduction in complications related to endoscopy of
      the upper gastrointestinal tract.

PMID- 15473408
TI  - Superior pulmonary sulcus tumor with Pancoast syndrome.

PMID- 15473409
TI  - Echocardiographic and clinical characteristics of pulmonary hypertension
      complicating pulmonary Langerhans cell histiocytosis.
AB  - OBJECTIVE: To determine the echocardiographic characteristics and impact on
      survival of pulmonary hypertension (PH) and correlations between
      echocardiographic and clinical variables in patients with pulmonary Langerhans
      cell histiocytosis (PLCH). PATIENTS AND METHODS: Of 123 adults seen at our
      institution between January 1976 and December 2002 with histologically proven
      PLCH, 17 underwent echocardiographic evaluation. Correlations were performed
      between echocardiographic measures of PH and clinical variables. Cumulative
      survival probabilities for patients with PH were estimated using the Kaplan-Meier
      method and were compared to a historical cohort of patients with PLCH using time
      dependent proportional hazard regression. RESULTS: Of the 17 patients, PH
      (estimated pulmonary artery systolic pressure [PASP] at rest, > 35 mm Hg) was
      present in 15. Thirteen patients (6 men; median PASP, 67 mm Hg; range, 41.2-90.6
      mm Hg) had no other known causes of PH. All patients were smokers. Nine patients
      had a PASP of more than 50 mm Hg. An inverse correlation was found between the
      forced vital capacity and PASP (r = -0.61; P = .03); no correlation was found
      between PASP and other pulmonary function parameters. Seven patients with a PASP
      greater than 65 mm Hg had an enlarged right ventricle with impaired systolic
      function. The development of PH in patients with PLCH was associated with
      increased mortality (hazard ratio, 22.8; 95% confidence interval, 7.6 to > 68.9;
      P < .001). CONCLUSION: Severe PH occurs in PLCH, correlates with the forced vital
      capacity, and has a significant impact on survival. Clinicians should consider
      echocardiographic screening for PH in all dyspneic patients with PLCH.

PMID- 15473410
TI  - Ovarian cancer: the neglected diagnosis.
AB  - OBJECTIVE: To investigate presenting signs and symptoms of ovarian cancer and
      stage of tumor in a community cohort of women with the diagnosis of ovarian
      cancer. PATIENTS AND METHODS: We reviewed retrospectively the medical records of
      all women who sought primary and specialty care in Olmsted County, Minnesota,
      between January 1, 1985, and December 31, 1997, to evaluate presenting symptoms,
      time from first symptom to diagnosis of ovarian cancer, and stage of tumor at
      diagnosis. RESULTS: Of 107 women with a diagnosis of ovarian cancer, the most
      commonly documented presenting symptom was crampy abdominal pain. Urinary
      symptoms and abdominal pain were the most commonly documented presenting symptom
      in patients with stage I and II ovarian cancers, whereas abdominal pain and
      increased abdominal girth were the most commonly documented symptoms in patients
      with stage III and IV cancer. Approximately 15% of tumors (n = 15) were found
      during routine evaluations or during a procedure for another problem. Less than
      25% of presenting symptoms (n = 24 women) related directly to the pelvis or were
      more traditional gynecologic symptoms. Delays in women seeking medical care,
      health care system issues, competing medical conditions, physicians' failure to
      follow up, and women not returning for follow-up were associated with longer time
      to diagnosis. CONCLUSION: Both stage I and II cancer are associated with
      symptoms, but few symptoms are directly related to the reproductive pelvic organs
      or unique to ovarian cancer. A longer interval from first sign or symptom to
      diagnosis of ovarian cancer is associated with both patient and health care
      system factors.

PMID- 15473411
TI  - Current and future treatment strategies for refractory angina.
AB  - Patients with refractory angina are not candidates for revascularization and have
      both class III or IV angina and objective evidence of ischemia despite optimal
      medical therapy. An estimated 300,000 to 900,000 patients in the United States
      have refractory angina, and 25,000 to 75,000 new cases are diagnosed each year.
      This review focuses on treatment strategies for refractory angina and includes
      the mechanism of action and clinical trial data for each strategy. The
      pharmacological agents that have been used are ranolazine, ivabradine,
      nicorandil, L-arginine, testosterone, and estrogen; currently, only L-arginine,
      testosterone, and estrogen are approved by the Food and Drug Administration.
      Results with the noninvasive treatments of enhanced external counterpulsation and
      transcutaneous electrical nerve stimulation are provided. Invasive treatment
      strategies including spinal cord stimulation, transmyocardial revascularization,
      percutaneous myocardial revascularization, and gene therapy are also reviewed.

PMID- 15473412
TI  - Using advanced search tools on PubMed for citation retrieval.
AB  - PubMed (www.pubmed.gov) provides health care professionals with free access to
      one of the largest searchable biomedical databases available. However, attempting
      to find relevant literature in PubMed without an understanding of basic search
      strategies and tools may be daunting and frustrating. In a previous issue of the
      Mayo Clinic Proceedings, we presented an overview of searching in PubMed and
      introduced its basic features. In this article, we build on this foundation and
      present advanced search tools designed to assist clinicians in performing
      efficient and focused literature searches.

PMID- 15473413
TI  - 73-year-old man with vomiting and fever.

PMID- 15473414
TI  - Family-based therapy for adolescents with anorexia nervosa.
AB  - Practice guidelines advocate a multidisciplinary approach to the treatment of
      adolescents with anorexia nervosa. A specific type of therapy in which the family
      plays an integral role has yielded good outcomes. We describe 2 patients who
      failed to respond to conventional care in a multidisciplinary setting and
      subsequently underwent family-based therapy with good results. Our findings
      suggest that enlisting the family in the treatment of adolescents with anorexia
      nervosa may lead to greater weight gain, shorter treatment duration, and reduced
      costs.

PMID- 15473415
TI  - Primary mammary (non-Hodgkin) lymphoma presenting as locally advanced breast
      cancer.
AB  - Primary mammary lymphoma is a rare tumor that presents commonly as a large mass
      with no specific mammographic appearance and can be confused with poorly
      differentiated carcinoma on frozen section. With appropriate treatment, this
      breast malignancy has a relatively good prognosis. We report a case of primary
      mammary non-Hodgkin lymphoma in a 74-year-old woman that originally presented as
      locally advanced breast cancer with secondary inflammatory skin changes. Clinical
      findings, diagnostic work-up, and follow-up are provided along with a review of
      the literature on primary mammary lymphoma.

PMID- 15473416
TI  - Extreme photosensitivity.

PMID- 15473417
TI  - A critique on contemporary reporting of likelihood ratios in test power analysis.

PMID- 15473418
TI  - Literature-searching strategies to improve the application of evidence-based
      clinical practice principles to stroke care.
AB  - The field of cerebrovascular disease is evolving more rapidly than ever. New
      evidence from primary research in stroke is available and should be guiding
      global changes in practice. Instead, there is a disappointing and ever-widening
      evidence-practice gap. Busy health care practitioners are encouraged to practice
      evidence-based medicine, but their skills in this field are deficient. The
      purpose of this article is to provide the steps necessary to quickly,
      efficiently, and independently locate high-quality, valid evidence-based
      information on stroke that can be applied in a point-of-care setting. A
      discussion of secondary stroke prevention highlights these steps.

PMID- 15473419
TI  - Secondary prevention strategies in ischemic stroke: identification and optimal
      management of modifiable risk factors.
AB  - The identification and treatment of modifiable Ischemic stroke risk factors, in
      addition to appropriate antithrombotic therapy, can reduce the likelihood of
      first or recurrent stroke, prevent long-term morbidity and mortality after first
      stroke or transient Ischemic attack, and lower health care costs. Long-term
      morbidity and mortality in patients with ischemic stroke includes patients with
      coronary artery disease. Therefore, in patients with ischemic stroke (especially
      those with carotid artery disease and lacunar disease), the goal is to prevent
      not only recurrent stroke but also coronary artery disease. Neurologists and
      general practitioners must be aware of the specific risk factors and
      recommendations for patients with ischemic stroke and apply the information
      systematically. We review known risk factors for ischemic stroke and current
      recommendations for treatment, focusing primarily on atherosclerotic risk factors
      as they apply to patients with stroke. In particular, recent data on hypertension
      and hyperlipidemia are described. In addition, we discuss the challenges in
      managing these risk factors and the potential strategies for overcoming them.

PMID- 15473420
TI  - Calculating likelihood ratios in patients with giant cell arteritis.

PMID- 15473421
TI  - Production and consumption of science in a global context.

PMID- 15473422
TI  - Immigrant youth mental health promotion in transnationalizing societies.

PMID- 15473423
TI  - [Gender theory and politics: historical fragments and current challenges].
AB  - This text approaches contemporary gender theories and politics focusing on the
      tensions permeating these theories. It briefly revisits historical aspects to
      introduce an understanding of the to the concept of gender in the field of
      Feminist Studies, and discusses the theoretical and political developments
      associated with its use. It presents some results from investigations that make
      the positions of the subject of woman, and particularly the subject of mother,
      problematic in discourses running through current health and education policies
      and programs. It concludes by suggesting that studies relating gender, health and
      education from this perspective contribute to understanding and outlining power
      structures that come into play with certain educational emphases, knowledge,
      diagnostic instruments, and ways of assisting and educating women, men and
      children in these areas today.

PMID- 15473424
TI  - [The practice of the community health agency in health promotion of and disease
      prevention].
AB  - This article discusses practices developed by the community health agency in the
      Family Health Program of Divinopolis--MG reporting on practices in the fields of
      Health Promotion and Disease Prevention, taking as main reference the principles
      established at the 1st International Health Promotion Conference, which took
      place in Canada in 1986. Field research was carried out by questionnaire, direct
      observation of work and open interviews with community health agencies. A
      qualitative approach was chosen in which the concepts and statements of the
      subjects were dealt with in the light of historical and dialectical materialism,
      and the organization and analysis of the discourses according to the Discourse of
      the Collective Subject. We conclude that the community health agency performs
      actions recommended by the Ministry of Health, and that its health promoting
      actions are confined to the creation of environments favorable to health, actions
      in the home. It works more widely in disease prevention, in individual actions,
      health education for the community and for groups at risk, and controlling
      infectious disease and parasites such as dengue and worms. Its focus of attention
      is predominantly the individual and not the family.

PMID- 15473425
TI  - [How do nurses perceive their role on health councils?].
AB  - This study is part of a Master's thesis on the participation of nurses on Health
      Councils and aims to analyze the perception nurses have of their role in these
      forums. A qualitative approach is used with a theoretical referential of
      Discourse Analysis. The subjects are nurses who have been members of Local and
      Municipal Health Councils in Goiania, Goias State, since 1995. The perceptions
      expressed are related to their concerns about not monopolizing the councils,
      about councils--especially local ones--being used for party political purposes,
      about avoiding corporate positions, about council autonomy, lack of
      infrastructure, political interference, lack of preparation on the part of
      professionals and the necessity of training for political quality, the
      contributions that they can make to discussion, reflection, group analysis,
      interventions and technical support. Hopeful perspectives refer to continued
      change in order to qualify a greater number of councilors, to the growing
      emancipation of people for citizenship and to the reliability of present
      administrations.

PMID- 15473426
TI  - [The performance of mastectomized women in group activities].
AB  - We aim to describe the reactions of women confronting mastectomy, and the
      feelings that emerged from group interaction. 10 women from the GEPAM group
      (Teaching, Research, Self-help and Assistance to Mastectomized Women Group) were
      interviewed in November and December 2001 and January 2002. Reactions in the face
      of mastectomy can be singled out as: depression, discrimination, adoption of new
      behavior and the need for social interaction. Group interaction revealed feelings
      of friendship and curiosity. These aspects lead us to understand that group
      activities are important in minimizing the conflicts associated with mastectomy
      and also in valuing of the feelings of these women, to provide more effective
      rehabilitation and better quality of life.

PMID- 15473427
TI  - [The struggle for survival of the child discharged from intensive care].
AB  - Pediatric intensive care units have significantly reduced childhood morbidity and
      mortality, and have generated a group of children with special care needs. The
      common sense family care they receive at home however has not been trained to
      attend to them, interfering in their quality of life and causing frequent returns
      to hospital. To know about discharge from intensive care is to go beyond survival
      and to also offer a better quality of life. To this end we developed an
      epidemiological method in two public health care facilities in Rio de Janeiro, to
      investigate the time and number of hospitalizations and type and quantity of
      diagnosis between 1994-1999, with children aged from 29 days to 12 years. The
      results show that 6.3% (85) of 1355 hospitalized children were considered with
      special care needs, with 9 hospitalizations of up to 60 days. To each
      hospitalization can be added one or two basic diagnoses revealing chronic
      conditions.

PMID- 15473429
TI  - [How psychiatric patients perceive their families: a two-sided mirror].
AB  - This study identifies how psychiatric patients perceive their families. We
      performed qualitative research, using open interview and life story narrative
      techniques. The data was analyzed using Thematic Analysis methodology, from which
      we identified two basic categories: Affection and Disaffection. Feelings related
      to disaffection were more frequent, allowing us to infer that the subjects suffer
      from difficulties in family relationships. On the other hand, the meaning of the
      family and the expectations held are variable and specific to each person. The
      study suggests the need for forms of assistance that take into account the
      subjective domain, by considering the perception and expectations of the patient
      regarding his/her family, and then planning an adequate therapeutic strategy.

PMID- 15473428
TI  - [Bioethical focus in the scientific production of nurses: characterization and
      analysis].
AB  - Bioethics raises ethical questions inherent to life, stimulated by biomedical and
      technological advances. Nursing has taken an interest in bioethical studies with
      the appearance of the first ethical studies based on gender relations. Here we
      undertake a quantitative-qualitative study of the scientific production of nurses
      in Brazil into Bioethics. The bibliographical survey considered postgraduate
      studies through CEPEn catalogs and articles published in national Nursing
      journals between 1990 and 2002. Reading and analysis of the material revealed
      that bioethical studies carried out by nurses are principally focused on the
      nursing professional. Production is seen to be sparse, with post-graduate studies
      containing the most examples.

PMID- 15473430
TI  - [Asymmetrical relationships: sexuality, health, and power in the military].
AB  - The article presents an excerpt from an investigation into male military police
      perceptions of STD/AIDS, emphasizing RELATIONS OF POWER, identifying
      interventions in sexual practice and consequently, on perception and exposure to
      the risk of STD/AIDS contamination. Focus group meetings enabled socialization of
      information, showing that the majority of participants acknowledge the risk of
      STD/AIDS contamination, although this is not necessarily converted into
      prevention. It registers the inequality between men and women regarding sexual
      practice and its possible consequences in the growing incidence of cases of
      sexually transmitted disease.

PMID- 15473431
TI  - [Validation of a nursing data collection instrument for hospitalized adult
      clients].
AB  - The objective of this study was to validate the data collection instrument used
      in adult hospitalization, verifying if the items permitted data collection that
      enabled the development of later phases of systematization of nursing care,
      improvement of its operation, and the construction of an instructional guide. The
      research was conducted in a Medical Clinic at the Lauro Wanderley University
      Hospital, (HULW), where data collection has taken place since 1984. The technique
      used for validation was to interview a focus group. The sample consisted of 13
      nurses, and the activities took place from September to December 2002. The result
      of the discussions enabled restructuring of the instrument according to the
      consensus obtained, adapting it to the most objective form for clinical use
      according to the characteristics of the clients.

PMID- 15473432
TI  - [Iodine contrast in computed tomography: preventing adverse reactions].
AB  - Computed tomography is an X-ray exam that has been widely indicated and chosen
      for diagnostic purposes, especially during the last few decades. However,
      although it is highly revealing, in several cases the procedure presents risks
      associated with exposure to radiation and to the iodine contrast medium. Few
      publications are available in the nursing literature regarding these issues.
      Therefore, a review of literature is presented, emphasizing exposure to iodine
      contrast and adverse reactions that may arise from its use. In addition, actions
      are described that can be taken by the health care team professionals to reduce
      the occurrence of such adverse events or minimize their severity.

PMID- 15473433
TI  - [The Pan-American Federation of Nursing Professionals: a vision and perspective
      for the 21st century].
AB  - This essay concerns the prospective vision of The Pan-American Federation of
      Nursing Professionals in the scenario of health and education in the new century.
      It discusses the concepts of association, leadership, and paths the profession
      has taken as a professional organization. It makes a brief historical study of
      the construction of nursing as profession and its organization as a corporation.
      In the second part it places FEPPEN in this context of nursing as corporation,
      revealing its aims and the specific struggles in which it has played an important
      role. Finally it discusses the role of associations in building a healthier and
      fairer society.

PMID- 15473434
TI  - [Nurse training from the competence perspective: a short reflection].
AB  - The new curriculum directives for undergraduate courses in the health area
      require reflection and awareness of the direction of nursing teaching. The
      transition between the basic curriculum and curriculum by directives; educational
      objectives and training by ability; ability in the working world and professional
      training; in addition to human and technical development, are some elements that
      need to become part of nurses' everyday practice in all the areas in which they
      work. It is important to start reflecting on these questions at this time, and
      that is the purpose of this text.

PMID- 15473435
TI  - [Progression of course content within the framework of curriculum requirements:
      gender in nursing education].
AB  - This article reviews the concept of gender in Nursing education at Federal
      University of Bahia based on Brazilian Curriculum Requirements for Graduate
      Nursing Programs. The possibility of inserting this concept as a progressive
      content into an integrated curriculum is presented, originating from experience
      obtained with a subject matter-based curriculum. The discussion of this proposal
      aims at contributing to other educational institutions which are currently
      experiencing a process of curriculum change. This article highlights some
      theoretical and methodological possibilities that might lead to an easier grasp
      of reality based on such concept. It even portrays the way this concept can be of
      use in understanding how institutions and health practices are put together and
      the ways in which they could be modified.

PMID- 15473436
TI  - [Doing and learning: a teaching/learning experience].
AB  - In this study, the authors describe the learning/teaching experience of the 2nd
      year of the Faculdade de Medicina de Marilia Nursing Course, which
      interdisciplinary curriculum has been implemented according to the PBL
      methodology since 1998. This curriculum seeks to articulate content,
      theory/practice and learning/service, in a continuous reconstruction process,
      with feedback through evaluation, which is considered to be an advance, yet which
      also contains some challenges.

PMID- 15473437
TI  - [Anatomy: the bodily order].
AB  - In this essay I try to show the source of the knowledge that determines a certain
      view that the healthcare team, particularly the nursing team, has developed on
      the body, especially the sick body. I understand that this knowledge determines
      ways of caring for the hospitalized bodies. Based on texts by Foucault I analyze
      the subject of Anatomy. I present a brief history of its construction as a field
      of knowledge since Versalius until today, when we find plastinated and digitized
      bodies. I highlight the cadaver as the student's first contact with a human body
      and observe that the illustrations contained in Anatomy books privilege male and
      white bodies. I characterize the body as a radically historical invention and
      observe that we are culturally trained to perceive it, in an organized way, from
      given viewpoints and by using certain lenses.

PMID- 15473438
TI  - Manage chronic care costs to bolster your bottom line.

PMID- 15473439
TI  - Henry Ford manages capitated patients with an eye on quality.
AB  - Henry Ford Health System in Detroit works closely with its health plan to manage
      globally capitated contracts. Get the inside scoop on their best strategies.

PMID- 15473440
TI  - Surveys indicate rise in office visits, increasing costs.
AB  - As the use of disease management and preventive care expands, people ages 45 or
      older are seeing their doctor more often, according to a CDC survey. With an
      aging population, experts believe physicians will be challenged by patients with
      multiple chronic conditions and will rely more heavily on information technology
      innovations.

PMID- 15473441
TI  - Medicare advantage enrollment predicted to nearly double by 2010.
AB  - A statistician at the Centers for Medicare & Medicaid Services talks about how
      well managed care controls costs for the Medicare Advantage population, and why
      capitation may be in for a boost as managed Medicare gains traction

PMID- 15473442
TI  - A special commitment to the elderly.

PMID- 15473443
TI  - Create success: find a mentor.

PMID- 15473444
TI  - Hypertrophic nails with palmoplantar hyperkeratosis.

PMID- 15473445
TI  - Osteoarthritis management today: minimizing pain and maximizing quality of life.

PMID- 15473446
TI  - Essential tremor in the older adult: coping with primary symptoms.

PMID- 15473447
TI  - Sophie's bones: a case study in osteoporosis.

PMID- 15473448
TI  - The myths and truths of mature intimacy: mature guidance for nurse practitioners.

PMID- 15473449
TI  - Documenting to improve pediatric asthma outcomes: practical tools for nurse
      practitioners.

PMID- 15473450
TI  - Abdominal pain: the diagnostic conundrum.

PMID- 15473451
TI  - Patient information. Coping with colds.

PMID- 15473452
TI  - Unemployed, but not idle.

PMID- 15473453
TI  - Carbon monoxide poisoning in tents--a review.
AB  - This review discusses the overlooked problem of carbon monoxide (CO) poisoning
      within small tents. It summarizes previous case reports, reviews the toxicity of
      CO, and attempts to draw conclusions from experimental work. Finally, practical
      recommendations are developed on avoiding CO poisoning within tents. The term
      carbon monoxide was used in a search of the Medline database covering the years
      1966 to 2003. The results were combined with the terms atmosphere or camps or
      stoves or climbs or mountains or tents or poisons. The resulting articles were
      reviewed, and those relevant to this problem were obtained. Hard copies were hand
      searched for further relevant articles until no more citations could be found.
      Three original articles were impossible to obtain but have been cited to assist
      others seeking to find them. Other data and articles were obtained from the
      Ministry of Defence but are unpublished for security reasons.

PMID- 15473454
TI  - Comparison of carbon monoxide levels during heating of ice and water to boiling
      point with a camping stove.
AB  - OBJECTIVES: To determine whether using a camping stove to bring a pan of ice to
      boiling point produces higher carbon monoxide (CO) concentration than would
      bringing a pan of water to boiling point. The hypothesis was that ice would cause
      greater CO concentration because of its greater flame-cooling effect and,
      consequently, more incomplete combustion. METHOD: This was a randomized,
      prospective observational study. After an initial pilot study, CO concentration
      was monitored during 10 trials for each of ice and water. A partially ventilated
      200-L cardboard box model was developed and then used inside a chamber at -6
      degrees C. Ice temperature and volume, water temperature and volume, pan size,
      and flame characteristics were all standardized. Temperature of the heated medium
      was monitored to determine time to boiling point. Carbon monoxide concentration
      was monitored every 30 seconds for the first 3 minutes, then every minute until
      the end of each 10-minute trial. RESULTS: There was no significant difference (P
      > .05) in CO production levels between ice and water. Each achieved a similar
      mean plateau level of approximately 400 ppm CO concentration with a similar rate
      of rise. However, significantly higher (P = .014) CO concentration occurred at 4
      and 5 minutes when the flame underwent a yellow flare; this occurred only on 3
      occasions when ice was the medium. CONCLUSION: There were no significant
      differences for CO production between bringing a pan of ice or water to boiling
      point. In a small number of ice trials, the presence of a yellow flame resulted
      in high CO concentration. Yellow flares might occur more often with ice or snow
      melting, but this has not been proven.

PMID- 15473455
TI  - Does pan diameter influence carbon monoxide levels during heating of water to
      boiling point with a camping stove?
AB  - OBJECTIVES: To determine whether pan diameter influences carbon monoxide (CO)
      concentration during heating of water to boiling point with a camping stove. The
      hypothesis was that increasing pan diameter increases CO concentration because of
      greater flame dispersal and a larger flame. METHOD: This was a randomized,
      prospective study. A Coleman Dual Fuel 533 stove was used to heat pans of water
      to boiling point, with CO concentration monitored every 30 seconds for 5 minutes.
      The stove was inside a partially ventilated 200-L cardboard box model that was
      inside an environmental chamber at -6 degrees C. Water temperature, water volume,
      and flame characteristics were all standardized. Ten trials were performed for
      each of 2 pan diameters (base diameters of 165 mm [small] and 220 mm [large]).
      RESULTS: There was a significant difference (P = .002) between the pans for CO
      levels at each measurement interval from 60 seconds onward. These differences
      were markedly larger after 90 seconds, with a mean difference of 185 ppm (95% CI
      115, 276 ppm) for all the results from 120 seconds onwards. CONCLUSION: This
      study has shown that there is significantly higher CO production with a large
      diameter pan compared with a small-diameter pan. These findings were evident by
      using a camping stove to heat water to boiling point when a maximum blue flame
      was present throughout. Thus, in enclosed environments it is recommended that
      small-diameter pans be used in an attempt to prevent high CO levels.

PMID- 15473456
TI  - Gender differences among long-distance backpackers: A prospective study of women
      Appalachian Trail backpackers.
AB  - OBJECTIVE: Backpacking is a popular recreational activity, yet the differential
      experiences of women are unknown. The objective was to compare women with men
      backpackers to determine the extent to which injuries and illnesses limit
      endurance outdoor recreational activities. METHODS: This was a prospective cohort
      surveillance survey of 334 persons who hiked the Appalachian Trail for > or =7
      days. At the end of their hike, 280 subjects completed a questionnaire. Male
      hikers served as controls for injury and illness. RESULTS: Women comprised 26%
      (72 of 280) of the sample. The mean (+/-SD) duration of hiking was 144 +/- 66
      days covering 1570 +/- 680 miles. Fifty-seven percent (41 of 72) of women and 72%
      (150 of 208) of men attained their goal (P = .02). The occurrence of individual
      musculoskeletal problems, such as strains, sprains, arthralgias, tendonitis, and
      fractures, were similar (P = .9) between sexes. The occurrence of diarrhea (56%)
      was also similar (relative risk [RR] 1.0; P = .9) between sexes. Of regularly
      menstruating women, 87% (43 of 49) had menstrual changes while hiking, such as
      change in frequency (45%) or character (43%) (RR 3.1; 95% CI, 2.0-4.8; P < .001).
      Shortened duration of menses was most common (41%). Amenorrhea occurred in 22%
      (11 of 49) of women, including 5 of 25 taking oral contraceptive pills (OCPs).
      Breakthrough, midcycle bleeding occurred in 20% (10 of 49) of women. CONCLUSIONS:
      Women had similar experiences as compared with men when backpacking. Menstrual
      changes were very common including amenorrhea. Prolonged amenorrhea raises
      concern for potential bone mineral density loss, and OCPs should be considered to
      prevent such loss.

PMID- 15473457
TI  - Morbidity and determinants of health on youth expeditions.
AB  - OBJECTIVE: To document the prevalence of illness and injury on youth expeditions
      and analyze specific determinants of health. METHODS: Two thousand nine hundred
      fifteen people, aged 15 to 18 years, traveled with a commercial company, World
      Challenge Expeditions Ltd, between June and September 2001. Adult team leaders
      were required to keep medical cards for each person. This study is a
      retrospective analysis of these medical cards. RESULTS: Completed medical cards
      were available for 2402 people (82%). There were no medical problems in 36% of
      people. Illness or injury was reported by 64% (mean, 2.0 medical problems per
      person). Of the medical problems, 6% were defined as serious, and 1% were
      admitted to the hospital. One fatality occurred. The five most prevalent medical
      problems were diarrhea (22%), nausea and vomiting (20%), cold or sore throat
      (11%), headache (11%), and trauma (10%). Girls reported 19% more medical problems
      than the boys reported. Gastrointestinal illness was significantly increased at
      high altitude. Illness and injury were most prevalent in South America and least
      prevalent in Australasia. CONCLUSIONS: Our results demonstrate that in young
      people traveling to remote parts of the world, illness and injury are common.
      Serious incidents are rare; however, the death of one person does highlight the
      dangers present. This study may help risk assessment for young people considering
      taking part in an expedition.

PMID- 15473458
TI  - Airway compromise after first rattlesnake envenomation.
AB  - The purpose of this report is to describe an unusual presentation of anaphylaxis
      after first-time rattlesnake envenomation. A patient on a medical toxicology
      inpatient service is presented who had signs of anaphylaxis, including airway
      compromise, after first-time rattlesnake envenomation. An epinephrine drip and
      oral intubation were initiated. This case is unusual in that dermal and
      gastrointestinal exposure may have been the primary sensitization process that
      preceded a severe anaphylactic reaction after envenomation. The patient's
      recovery was prolonged. In conclusion, rattlesnake envenomation may result in
      rapidly progressive airway compromise, possibly caused by anaphylaxis in patients
      with previous dermal or gastrointestinal exposure to snake proteins.

PMID- 15473459
TI  - Moray eel attack in the tropics: a case report and review of the literature.
AB  - As more people use the oceans for recreational purposes, encounters with
      potentially dangerous sea creatures are becoming more common. We report the case
      of a scuba diver bitten by a moray eel off the coast of Cuba. The diver received
      an extensive crush avulsion injury with near loss of his right upper arm. A
      review of the existing literature identifies the significant characteristics of
      such attacks. Given the potential seriousness and complications of these attacks,
      a greater awareness among both treating physicians and emergency personnel may
      improve overall management of injuries. In addition, greater respect for moray
      eels among divers and other ocean users may decrease the likelihood of serious
      eel encounters.

PMID- 15473460
TI  - Use of the Gamow Bag by EMT-basic park rangers for treatment of high-altitude
      pulmonary edema and high-altitude cerebral edema.
AB  - As part of an emergency medical system protocol, national park service rangers
      certified at the level of an emergency medical technician-basic (EMT-B) are
      taught to recognize and treat high-altitude pulmonary edema and high-altitude
      cerebral edema. In Sequoia and Kings Canyon National Parks, this is done with the
      assistance of physician on-line medical control as a backup. High-altitude
      pulmonary edema and high-altitude cerebral edema are both potentially fatal
      altitude illnesses that can be particularly problematic in the backcountry, where
      evacuation may be delayed. We report a case of high-altitude pulmonary edema and
      high-altitude cerebral edema occurring at moderate altitude that was successfully
      treated by park rangers with the Gamow Bag.

PMID- 15473461
TI  - Self-assessment of acute mountain sickness in adolescents: a pilot study.
AB  - OBJECTIVE: To perform a pilot study exploring the prevalence of acute mountain
      sickness (AMS) in adolescents on ascent to altitude and evaluating whether this
      age group is capable of self-assessment of AMS using the Lake Louise scoring
      system. METHODS: Twelve teenagers aged 15 to 18 years old (5 girls) traveled for
      21 days between 2400 and 5500 m. Each member of the expedition completed a Lake
      Louise self-assessment questionnaire on a daily basis. Group leaders (nonmedical)
      were informed about any subject with a score of 3 or more. Appropriate treatments
      were then initiated. Detailed analysis of data was undertaken on return to the
      UK. RESULTS: There was 100% completion of 252 questionnaires. Eleven of the 12
      subjects (91.7%) had symptom scores greater than or equal to 3, consistent with a
      diagnosis of AMS, on at least one day (range, 0-8). Symptoms of AMS were more
      common in the female group members (P = .041). CONCLUSIONS: AMS is a common
      problem among adolescents. There are increasing numbers of adolescents traveling
      to high altitudes, and there appears to be a lack of information about the
      prevalence of AMS in this age group. Motivated adolescents seemed capable of self
      monitoring for AMS using the Lake Louise questionnaire. Combined with an
      appropriate ascent profile and support, we feel this approach may contribute to
      safety in the mountains and merits further study.

PMID- 15473462
TI  - A review of venomous animal bites and stings in pregnant patients.
AB  - This is a review of Medline and PubMed articles on venomous animal bites and
      stings during pregnancy reported in English literature from 1966 to 2002. Eighty
      five venomous snakebites were reported in pregnant women. Although there are
      frequent anecdotal reports of scorpion stings in pregnant women, few case reports
      are documented. Other venomous animal bites or stings to pregnant women that have
      been reported include spiders, jellyfish, and insects, and these are described.
      Adverse reproductive and teratogenic effects of venoms on gravid animals are also
      briefly reviewed. Although uncommon, venomous bites and stings during pregnancy
      may have significant adverse effects on the fetus and the mother.

PMID- 15473463
TI  - Preliminary report on the beneficial effect of chloromycetin in the treatment of
      typhoid fever. 1948.

PMID- 15473464
TI  - Do jungle boots stop jungle rot?

PMID- 15473465
TI  - Ascorbate, blood-brain barrier function and acute mountain sickness: a radical
      hypothesis.

PMID- 15473466
TI  - Heyde's syndrome: a review.
AB  - Bleeding from gastrointestinal angiodysplasia in patients with aortic stenosis
      (AS), termed Heyde's syndrome, has been recognized for many years. Intestinal
      angiodysplasia (IA) and AS are chronic degenerative diseases that are often
      asymptomatic, with a higher prevalence in the population than is clinically
      apparent. The incidence of both conditions increases with age, and both are
      associated with traditional cardiovascular risk factors. Many studies suggest
      that there is an increased prevalence of IA in AS and vice versa, but there is
      wide variation between studies. Evidence is mounting that severe AS may cause
      Type 2 acquired von Willebrand's disease, also termed von Willebrand's syndrome.
      This involves loss of the large multimers, which are required to maintain
      hemostasis in high flow conditions, such as occur in angiodysplastic
      arteriovenous malformations. Heyde's syndrome appears to consist of bleeding from
      previously latent intestinal angiodysplasia as a result of this acquired
      hematological defect, which is associated with aortic stenosis. Treatment options
      include localization of angiodysplastic bleeding points with cauterization, but
      this is associated with a high recurrence rate. Aortic valve replacement has been
      shown to improve the hematological abnormalities, and this is paralleled by
      clinical improvements. Valve replacement appears to offer the best hope of long
      term resolution of the bleeding, and should be considered in most cases,
      particularly in those in whom the AS is symptomatic. In those patients deemed
      unfit for surgery in whom no bleeding point can be identified, recurrent blood
      transfusions may offer some symptomatic relief.

PMID- 15473467
TI  - An epidemiological study of Heyde's syndrome: an association between aortic
      stenosis and gastrointestinal bleeding.
AB  - BACKGROUND AND AIM OF THE STUDY: An association between aortic stenosis (AS) and
      gastrointestinal (GI) bleeding attributed to intestinal angiodysplasia has been
      termed Heyde's syndrome. Case-control studies of patients with AS or intestinal
      angiodysplasia assessing the degree of association have produced discrepant
      findings. METHODS: Data were examined for all patients discharged from public
      hospitals in the Republic of Ireland between 1997 and 2001 (3.8 million events)
      with a primary or secondary discharge diagnosis of AS (ICD-9-CM code 424.1), GI
      bleeding presumed due to intestinal angiodysplasia (ICD-9-CM codes 569.84,
      569.85, 578.1, 578.9), or both. Proportions were compared using chi-squared
      testing. RESULTS: There was a significant (p <0.0001) association between AS and
      GI bleeding, with an odds ratio of 4.5 (95% confidence interval 3.0-6.8). Age was
      a significant confounding factor; patients with both conditions were
      significantly older than patients with one or none of the conditions (p <0.0001).
      The incidence of GI bleeding in patients with AS was 0.9%, and the incidence of
      AS in patients with GI bleeding was 1.5%. CONCLUSION: The results of this large
      retrospective analysis support the existence of an association between AS and GI
      bleeding presumed due to intestinal angiodysplasia. However, the percentage of
      patients with both conditions was low, and this may explain why some smaller
      studies have failed to demonstrate such an association.

PMID- 15473468
TI  - A versatile technique for aortic root replacement without pre-manufactured
      composite graft: a 12-year experience.
AB  - BACKGROUND AND AIM OF THE STUDY: Replacement of the aortic root is the treatment
      of choice for aneurysmal dilatation. Many modifications of the Bentall technique
      have been described, as have valve-sparing procedures. The study aim was to
      determine the outcome of a versatile modification of composite replacement that
      has been adopted over the past 12 years. Separate graft and prosthetic valve
      components were used to allow freedom of valve choice and the use of an
      appropriately sized graft for the distal aortic anastomosis. METHODS: Between
      January 1990 and March 2002, 59 patients (45 males, 14 females; mean age 56 +/-
      14 years) underwent aortic root replacement using this technique. Indications for
      surgery were elective in 35 patients and emergent (usually type A aortic
      dissection) in 24. The range of valve prostheses used, their size, and the size
      of aortic graft used in each case was assessed. Durations of ischemia and
      cardiopulmonary bypass were recorded, as was postoperative blood loss and
      subsequent patient progress, including valve-related events, perioperative
      mortality and actuarial survival. RESULTS: A wide range of aortic graft sizes was
      combined with both mechanical and tissue valves (from 1-7 mm larger in diameter).
      Median postoperative blood loss was 550 ml (IQR 400-800 ml). Perioperative
      mortality was 5.1%. There were no valve- or technique-related deaths, and the
      median actuarial survival was 13.17 years. During a 12-year follow up there were
      no proximal aortic reoperations. CONCLUSIONS: This technique had favorable
      perioperative mortality, produced a secure proximal suture line, and allowed the
      surgeon free choice of both valve type and size of aortic graft. This minimized
      tension at the distal suture line, and produced good hemostasis, especially in
      those patients with fragile dissected tissues.

PMID- 15473469
TI  - Effects of valve replacement on left ventricular function in patients with aortic
      regurgitation and severe ventricular disease.
AB  - BACKGROUND AND AIM OF THE STUDY: Longstanding aortic regurgitation (AR) can
      result in left ventricular (LV) dysfunction that may reverse after aortic valve
      replacement (AVR). Stentless valves may result in a more rapid recovery in
      function due to a more physiological flow and lower outflow resistance. METHODS:
      The effect of AVR on LV function was studied in 47 patients who received either a
      stentless (n = 33) or stented (n = 14) valve for isolated AR. All patients had
      evidence of pre-existing LV dysfunction (end-systolic dimension (ESD) >50 mm).
      Patients were studied using transthoracic echocardiography at baseline,
      postoperatively, and at 2.5-year follow up. RESULTS: Preoperatively, there were
      no differences in LV dimensions. The end-diastolic dimension fell from 75 +/- 10
      mm to 61 +/- 10 mm postoperatively and to 52 +/- 10 mm at follow up in the
      stentless group (p <0.001), and ESD fell from 54 +/- 10 mm to 36 +/- 8 mm at
      follow up (p <0.001). There were no significant early changes in patients who
      received stented valves, though LV dimensions fell at follow up. Fractional
      shortening (FS) increased from 25 +/- 8% in the postoperative period to 31 +/- 7%
      in the stentless group (p <0.001), but there was no change in the stented group
      (20 +/- 7% versus 23 +/- 8%). In the stentless group, LV mass fell from 366 +/-
      104 g to 276 +/- 68 g postoperatively and to 219 +/- 79 g at follow up (p
      <0.001); there was no postoperative change in the stented group, though a late
      reduction occurred, from 349 +/- 51 g preoperatively to 265 +/- 61 g at follow up
      (p = 0.06). CONCLUSION: For patients with AR and LV dysfunction, AVR with a
      stentless prosthesis offers early reductions in LV dimensions, improved LV
      function, and regression of LV mass. In patients who received a stented valve,
      these improvements were delayed and less complete. Hence, for some patients with
      AR and LV dysfunction, a stentless prosthesis may be preferable.

PMID- 15473470
TI  - Hemodynamic performance on exercise: comparison of a stentless and stented
      biological aortic valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: Although stentless valves are expected to be
      hemodynamically superior to stented valves, the results of comparative trials
      have been inconsistent. The study aim was to compare hemodynamic function at rest
      and on exercise in 50 stentless and stented biological replacement aortic valves
      METHODS: Twenty-one patients with a Toronto stentless porcine valve and 29 with a
      Perimount stented bovine pericardial valve were exercised using a bicycle
      ergometer. Echocardiography was performed before, and during exercise testing.
      RESULTS: Patients with either valve type were exercised to a similar degree.
      Transaortic resistance was slightly lower in the Perimount compared with the
      Toronto at rest (p = 0.03) and at peak exercise (p = 0.04), and flow was higher
      in the Perimount at rest (p = 0.007), but not at peak exercise. There were no
      significant differences between the valve types in peak velocity, mean pressure
      difference or effective orifice area either at rest or on peak exercise.
      CONCLUSION: There were no clinically significant differences in hemodynamic
      function between the stented and stentless biological valves chosen for
      comparison either at rest or during bicycle exercise.

PMID- 15473471
TI  - 'BioGlue' for the repair of aortic insufficiency in acute aortic dissection.
AB  - BACKGROUND AND AIM OF THE STUDY: Concern has been raised regarding the late
      effects of tissue glues. Herein is described the authors' experience with a new
      bioadhesive (BioGlue; Cryolife) for repair of the aortic root in acute
      dissection. METHODS: BioGlue is composed of bovine serum albumin (BSA) and
      glutaraldehyde. Glutaraldehyde exposure causes the lysine molecules of BSA,
      extracellular proteins and cell surfaces to bind to each other, creating a strong
      scaffold. Between January 2001 and January 2003, BioGlue was used to repair the
      aortic root in 22 patients with acute aortic dissection. Moderate or severe
      insufficiency was present in 16 cases, and mild insufficiency in six. The
      mechanism of insufficiency was commissure detachment in 15 cases, penetration of
      the intimal flap into the valve in three, and dilatation of the sinotubular
      junction in four. The aortic valve was resuspended to the aortic wall using
      pledgeted sutures. BioGlue was used to glue the dissected layers of the aortic
      root and create stronger tissue for sewing. Two patients required complete
      resection of the sinuses and aortic root remodeling with a Dacron graft. RESULTS:
      There were two operative deaths. Postoperative transesophageal echocardiography
      showed mild or no aortic insufficiency in 18 patients, and moderate insufficiency
      in two. During follow up (mean 16 months), none of the patients required
      reoperation for proximal redissection, delayed rupture, or aortic insufficiency.
      CONCLUSION: BioGlue is useful for aortic valve repair in aortic dissection. It is
      less toxic and has a stronger adhesive effect than the older surgical glues, and
      is expected to have better long-term results.

PMID- 15473472
TI  - Ten-year follow up after autologous rectus abdominis fascia sheath patch repair
      of aortic root abscess.
AB  - The infection of aortic annular tissue is a life-threatening complication of
      aortic valve endocarditis, the survival of which is usually with immediate
      surgical intervention. Optimal surgical techniques include aortic valve
      replacement with an aortic or pulmonary homograft, and reconstruction of cardiac
      structures with autologous pericardium. Here, two cases are reported with
      extensive aortic root infection and partial left ventricular-aortic dehiscence,
      who underwent left ventricular outflow tract reconstruction using a rectus
      abdominis fascia patch and aortic valve replacement with a Carpentier-Edwards
      porcine bioprosthetic graft. Both patients did well perioperatively and for 10
      years postoperatively. The results may encourage alternative surgical strategies
      to be used when aortic valve homografts or autologous pericardium are
      unavailable. Notably, autologous rectus fascia patches showed excellent
      performance in the reconstruction of left ventricular outflow tract destruction
      associated with aortic root abscess.

PMID- 15473473
TI  - Anterior leaflet augmentation with autologous pericardium for mitral repair in
      rheumatic valve insufficiency.
AB  - BACKGROUND AND AIM OF THE STUDY: The mechanism of insufficiency in rheumatic
      valve disease includes annulus dilatation and restricted leaflet motion. In order
      to improve the treatment of restriction, the anterior mitral leaflet (AML) can be
      augmented with a piece of glutaraldehyde-treated autologous pericardium. METHODS:
      Between January 1995 and December 1999, among 274 patients referred for rheumatic
      mitral disease, 143 (52%) underwent a valve repair. Of these patients, 81% had
      pure regurgitation and 19% had significant associated stenosis. Ring annuloplasty
      was used in all cases. Techniques used to treat the restrictive component of the
      regurgitation were compared in two consecutive cohorts of patients, either with
      (n = 62) or without (n = 81) AML augmentation. Mean patient age was 42 +/- 3
      years, and all preoperative variables were comparable except for the incidence of
      redo patients, who all underwent AML extension. RESULTS: In-hospital mortality
      was 0.7% (n = 1 with AML extension), and there was one early reoperation for
      pericardial patch dehiscence. After a mean follow up of 3.2 years, there was one
      sudden death (no AML extension). The reoperation rate was lower with (2.5%) than
      without (12.9%) AML augmentation (p <0.05). Echocardiography showed a lower
      incidence in recurrence of mitral insufficiency when AML augmentation was
      performed (grade 2, 9% versus grade 3, 3%) as compared to no AML augmentation
      (grade 2, 35% versus grade 3, 14%) (p <0.05). The mitral orifice area was larger
      (AML augmentation 2.2 +/- 0.3 cm versus no AML augmentation 1.8 +/- 0.4 cm2).
      CONCLUSION: Ring annuloplasty alone failed to correct rheumatic mitral
      insufficiency in all cases. AML augmentation improved the quality of the repair,
      and decreased the risk of reoperation.

PMID- 15473474
TI  - Current results of combined coronary artery bypass grafting and mitral
      annuloplasty in patients with moderate ischemic mitral regurgitation.
AB  - BACKGROUND AND AIM OF THE STUDY: Combined coronary artery bypass grafting (CABG)
      and mitral annuloplasty for ischemic mitral regurgitation (MR) is historically
      associated with high operative mortality, and remains controversial in the
      setting of moderate ischemic MR. Herein, operative mortality rates in patients
      undergoing combined CABG and mitral annuloplasty for moderate ischemic MR were
      examined. METHODS: Between January 1992 and August 1999, 108 patients with
      moderate (grade 3+) ischemic MR and coronary artery disease underwent combined
      CABG and mitral annuloplasty. Univariable analysis was used to identify
      perioperative risk factors associated with operative mortality in patients
      undergoing surgery during two different time periods (1992-95 versus 1996-99).
      Bivariable logistic regression was used to evaluate the possible effect of era on
      operative mortality, while controlling for potential confounders. RESULTS: The
      overall operative mortality was 6.4%. During 1992-95 the operative mortality was
      14% (4/28), but fell to 3.7% (3/80) during 1996-99 (p = 0.07). Patients from the
      earlier period were more likely to have unstable angina, worse NYHA functional
      class, and preoperative atrial fibrillation. Patients from the latter period were
      more likely to have peripheral vascular disease and chronic obstructive pulmonary
      disease. The unadjusted odds ratio (OR) for operative mortality associated with
      the earlier era was 4.3 (95% CI 9-20.8; p = 0.07). In the bivariable logistic
      regression models, where patient characteristics that potentially were
      responsible for the difference in mortality were added, the OR for operative
      mortality associated with the 1992-95 era ranged from 3.4 to 6.7. None of the
      patient characteristics appreciably reduced this risk. CONCLUSION: Recent
      decreased operative mortality in combined CABG and mitral annuloplasty for
      moderate ischemic MR suggests that a more liberal application of this approach
      may be warranted.

PMID- 15473475
TI  - Surgical treatment of infective mitral valve endocarditis.
AB  - BACKGROUND AND AIM OF THE STUDY: The approach to mitral valve endocarditis is a
      surgical challenge, and the optimal procedure remains a matter of debate. In this
      condition, mitral valve repair appears feasible, but its long-term effects--as
      opposed to more often practiced valve replacement--have not yet been determined.
      Herein, the authors' experience of surgical treatment of infective mitral valve
      endocarditis is presented, with reference to surgical replacement or
      reconstruction. METHODS: A retrospective analysis was performed of all patients
      with infective native mitral valve endocarditis treated surgically at the
      University Hospital Zurich and the City Hospital Triemli Zurich between 1980 and
      1996. Of 154 patients, 97 (63%) underwent mitral valve replacement, and 57 (37%)
      mitral valve reconstruction. RESULTS: The 30-day mortality was 3.2% (5/154); 4%
      (4/97) after replacement and 1.7% (1/57) after reconstruction (p = 0.67).
      Survival (Kaplan-Meier) was 93%, 81% and 61% after one, five and 10 years,
      respectively. There was no significant difference between valve replacement and
      reconstruction in terms of long-term survival (p = 0.15), but there was a trend
      towards better survival after reconstruction than replacement if only cardiac
      deaths were considered (p = 0.1). At follow up, reconstruction patients were
      significantly less frequently symptomatic (NYHA class III/IV) than replacement
      patients (0% versus 29%; p = 0.002), had a lower incidence of atrial fibrillation
      and need for pacemaker implantation (29% versus 47%; p = 0.04), and tended to
      have less dyspnea in daily life (20% versus 38%; p = 0.07). Reoperation in
      patients surviving more than 30 days was more common in replacement than in
      reconstruction patients. CONCLUSION: The present data suggest a trend for better
      clinical outcome after mitral valve reconstruction than after replacement when
      treating mitral valve endocarditis. These results encourage mitral valve
      reconstruction in mitral valve endocarditis, but recommendations to clinicians
      undertaking surgery on mitral valve endocarditis must be made with caution.

PMID- 15473476
TI  - Balloon mitral valvotomy after surgical commissurotomy: clinical and hemodynamic
      results of a large, single-center study.
AB  - BACKGROUND AND AIM OF THE STUDY: Patients with restenosis after open or closed
      surgical commissurotomy (SC) often demonstrate more severe valve degeneration
      than patients without prior surgery. This may affect the result of balloon mitral
      valvotomy (BMV) in this patient group. METHODS: The immediate- and long-term
      results (maximum 106 months; mean 26 months) of BMV with the Inoue balloon in
      patients with prior SC were compared with findings in patients without prior
      surgery. Between February 1989 and July 2001, a total of 1,156 BMV interventions
      was performed, of which 127 were conducted in patients (106 women, 21 men; mean
      age 56 +/- 12 years) with prior SC. RESULTS: After BMV, the mitral valve area
      (MVA) increased from 1.0 +/- 0.2 cm2 to 1.6 +/- 0.4 cm2 after SC compared with
      1.0 +/- 0.3 cm2 to 1.8 +/- 0.4 cm2 without SC. After three months, the average
      MVA was 1.7 +/- 0.3 cm2 in both patient groups. The mean NYHA class improved from
      2.8 to 2.0 (after SC) versus 2.7 to 1.8 (no SC) three months after BMV. The main
      complications were cardiac tamponade in three patients (2.4 %), and more than
      moderate mitral regurgitation (grade 2+) in six (4.7 %) compared to 5.8% in no-SC
      patients. CONCLUSION: In view of the satisfactory clinical and hemodynamic
      results, BMV with the Inoue balloon can be considered the treatment of choice for
      mitral valve restenosis after SC in selected patients.

PMID- 15473477
TI  - Early results with stentless mitral valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: Implantation of a chordally supported stentless
      mitral valve (SMV) may be the strategy of choice for patients with severe
      degenerative mitral valve disease. Herein, the early clinical results of this
      surgical technique were analyzed. METHODS: Since August 1997, 52 patients (36
      females, 16 males; mean age 68.0 +/- 8.5 years) each received a SMV (Quattro; St.
      Jude Medical Inc.) at the authors' institution. The underlying disease was
      predominant mitral stenosis (n = 26), incompetence (n = 17) and combined lesion
      (n = 9). The mean NYHA class was 3.1 +/- 0.6, left ventricular ejection fraction
      64 +/-13%, and cardiac index 2.1 +/- 0.8 1/min/m2. RESULTS: SMV implantation was
      performed using either a conventional sternotomy (n = 33) or a lateral
      minithoracotomy (n = 19). The mean implanted valve size was 29.2 +/- 1.7 mm, and
      mean cross-clamp time 81 +/- 33 min. Reoperation was required in six patients:
      two for paravalvular leakage, two for functional stenosis (both 26 mm valves), in
      one patient for pannus formation with underlying collagenosis, and in one for
      papillary flap rupture at five years. One patient died perioperatively, one died
      after reoperation at one year, and five patients died at longer follow up, from
      non-cardiac causes. Hemodynamic function was shown to be normal on
      echocardiography. CONCLUSION: Intermediate-term results after SMV implantation
      were promising. Preservation of annuloventricular continuity led to good left
      ventricular function, but long-term durability remains to be proven.

PMID- 15473478
TI  - Increases in mitral leaflet radii of curvature with chronic ischemic mitral
      regurgitation.
AB  - BACKGROUND AND AIM OF THE STUDY: Leaflet curvature is a primary determinant of
      leaflet stress, but no quantitative in-vivo leaflet curvature data exist. Chronic
      ischemic mitral regurgitation (CIMR) is associated with remodeling of the
      valvular-ventricular complex. It was hypothesized that leaflet radii of curvature
      (ROC) would change with such remodeling. METHODS: Twelve sheep had placement of
      radiopaque markers on the anterior (APM) and posterior (PPM) papillary muscles,
      mitral annulus, and anterior (AL) and posterior leaflet (PL) midlines. After 8 +/
      2 days, videofluoroscopy provided baseline 3-D marker data prior to creating
      inferior myocardial infarction (MI) by snare occlusion of the obtuse marginal
      coronary arteries. After 7 +/- 1 weeks, the animals were re-studied; 3-D marker
      coordinates were used to determine end-systolic leaflet ROC, leaflet length,
      annular septal-lateral diameter, and the distance of each papillary muscle to the
      mid-septal annulus and each commissure. RESULTS: Before and after CIMR, the AL
      had compound curvature, and CIMR increased ROC of both curves (proximal ROC 1.27
      +/- 0.59 to 1.38 +/- 0.60 cm (p <0.05); distal ROC 1.41 +/- 0.61 to 2.60 +/- 1.52
      cm (p < 0.05)). The PL ROC also increased with CIMR (from 2.01 +/- 1.40 to 3.46
      +/- 3.93) (p <0.05). Multiple regression analysis determined that annular septal
      lateral diameter (proximal AL and distal AL), distance from the APM to anterior
      commissure (distal AL), and PPM to mid-septal annulus (PL) were independent
      predictors of leaflet ROC. CONCLUSION: CIMR increased ROC of both the AL and PL.
      Leaflet extension may be a compensatory mechanism to minimize the regurgitant
      orifice, but the attendant increase in ROC will tend to augment leaflet stress.
      Annular and subvalvular geometry both affect leaflet curvature, and should be
      considered during mitral repair. These novel quantitative in-vivo data are now
      available for modification of finite element models, and for comparison to finite
      element model output.

PMID- 15473479
TI  - Mitral valve hemorrhage and mitral annulus shrinkage in rabbits with transient
      ventricular bigeminies induced by vagal stimulation.
AB  - BACKGROUND AND AIM OF THE STUDY: Cervical vagal stimulation in rabbits frequently
      induces transient ventricular bigeminies, followed by mitral regurgitation
      lasting a few days, and development of peculiar lesions of the mitral complex.
      The present study investigated early lesions of the mitral valve and subsequent
      deformation of the mitral annulus associated with ventricular bigeminies in this
      animal model METHODS: A 1-min period of right cervical vagal electrical
      stimulation was repeated in anesthetized rabbits under ECG monitoring. Animals
      were sacrificed at 1 h after stimulation to investigate early mitral valve
      lesions (n = 71; group A), or after one week for measurement of mitral annulus
      area, using photographic planimetry (n = 56; group B). RESULTS: Ventricular
      bigeminies were recorded during vagal stimulation in 72% of group A (n = 51), and
      73% of group B (n = 41). The most prominent early mitral valve lesion comprised
      widespread punctate hemorrhages over the chordae and leaflets, which developed in
      most animals with ventricular bigeminies (88%), but rarely in those without
      ventricular bigeminies (5%). This inter-group difference was highly significant
      (p <0.001). Gross examinations performed at one week after vagal stimulation
      revealed a deformed mitral annulus resulting from stiff, edematous periannular
      myocardial tissues. Animals with ventricular bigeminies displayed a significantly
      smaller mitral annulus area than those without ventricular bigeminies (26.8 +/-
      1.0 versus 31.7 +/- 1.2 mm2; p <0.01). CONCLUSION: Early mitral valve hemorrhage
      and later mitral annulus shrinkage occur following vagus-induced transient
      ventricular bigeminies. This may result from unusual mechanical stress on the
      mitral complex secondary to distorted ventricular contraction in the context of
      ventricular bigeminies.

PMID- 15473480
TI  - Clinical correlates and mortality of hemodynamically significant tricuspid
      regurgitation.
AB  - BACKGROUND AND AIM OF STUDY: Limited data exist regarding the etiologies and
      prognostic significance of severe tricuspid regurgitation (TR) in the modern
      medical era. This retrospective chart review examines the causes of, and
      mortality associated with, hemodynamically significant TR. METHODS: The database
      of the echocardiography laboratory at a major academic medical center was
      searched from August 2000 to October 2001, identifying 91 patients (1.2%) with
      transthoracic echocardiograms demonstrating moderate-severe or severe TR. A total
      of 77 available charts was reviewed retrospectively for medical history,
      examination and electrocardiogram findings. The underlying cause of each
      patient's TR was determined by compiling data from the chart and echocardiogram.
      All deaths were recorded from the date of echocardiography until September 2002.
      RESULTS: A cause for TR was determined in 96% of patients. Functional TR due to
      right ventricular pressure or volume overload was found in 85.5% of patients,
      while 14.5% had primary TR due to organic abnormalities of the tricuspid valve
      leaflets. Conditions associated with significant TR included pulmonary
      hypertension (46%), ischemic cardiomyopathy (25%), non-ischemic dilated
      cardiomyopathy (8%), Ebstein's anomaly (4%), rheumatic heart disease (4%),
      endocarditis (4%), tricuspid valve prolapse (2%), and severe mitral valve disease
      (2%). Of 37 patients (44.6%) who died, 17 (21%) did so within one month of the
      echocardiogram. CONCLUSION: Among patients presenting to a tertiary medical
      center, hemodynamically significant TR was more commonly functional than due to
      organic tricuspid valve disease. The most frequently associated diseases included
      pulmonary hypertension and cardiomyopathy. Significant TR may be a marker of
      increased mortality risk as it reflects the severity of underlying disease.
      Further studies in this area are warranted.

PMID- 15473481
TI  - Isolated congenital tricuspid insufficiency associated with right-sided
      congenital partial absence of the pericardium.
AB  - A unique case of successfully treated congenital tricuspid insufficiency (CTI)
      associated with partial absence of the right pericardium is described, and the
      clinical implications are discussed.

PMID- 15473482
TI  - Flat or curved pericardial aortic valve cusps: a finite element study.
AB  - BACKGROUND AND AIM OF THE STUDY: The finite element method (FEM) has frequently
      been used to investigate the behavior of the aortic valve, but studies on the
      performance and behavior of free-hand autologous pericardial aortic valves
      reconstructed using specially designed valve molds have not been performed. The
      study aim was to demonstrate the effectiveness of a three-dimensional (3-D) cusp
      of the authors' design (H-Mold) versus a two-dimensional (2-D) (flat) cusp using
      a FEM to compare stress distribution and leaflet contact properties. METHODS:
      Solid models of the aortic root and valve cusps were constructed using a computer
      aided design package. All models had different free edge lengths and surface
      areas, but a constant leaflet attachment length corresponding to a 19 mm annulus
      diameter. A static pressure of 80 mmHg was applied to all models. RESULTS: The
      maximum von Mises stress value in the H-Mold at the cusp commissure was 34.5%
      lower than the stress value in the flat leaflet, while the contact area in the H
      Mold leaflet was 85.7% greater than that of the flat leaflet. The length of
      leaflet free edge greatly influenced maximum von Mises stress intensity at the
      commissures, and the contact area between leaflets was mainly affected by the
      geometric shape of the leaflet and its surface area. CONCLUSION: 3-D leaflet
      geometry was found positively to influence leaflet stress distribution and
      coaptation. This geometry should have a significant impact on the reliability and
      long-term durability of pericardial aortic valve reconstruction.

PMID- 15473483
TI  - Specific regional and directional contractile responses of aortic cusp tissue.
AB  - BACKGROUND AND AIM OF THE STUDY: The control of valve size and function is a
      dynamic process that may be modulated by vasoactive factors. The exact response
      of different regions of the cusp tissue with regard to extent and direction could
      influence valve shape, function and response to stress. METHODS: Porcine aortic
      valve cusps were cut into either circumferential (basal, belly and coapting edge)
      or radial (left, center and right) strips. Together with an intact cusp
      orientated circumferentially, specimens were set up in isolated organ baths.
      RESULTS: In response to 90 mM KCI, the belly of the cusp (0.66 +/- 0.05 mN; p
      <0.05) was significantly more responsive than either the basal region (0.41 +/-
      0.06 mN) or the coapting edge (0.31 +/- 0.03 mN) and all three regions of
      radially orientated strips (left: 0.13 +/- 0.02 mN; center: 0.23 +/- 0.04 mN;
      right: 0.11 +/- 0.03 mN). All strips showed contraction to endothelin-1 (10(-9)
      to 10(-7) M). When corrected for weight, the responses of the basal (15.2 +/- 1.8
      mN/g) and belly (11.3 +/- 1.5 mN/g) regions were significantly greater than that
      of the coapting edge (8.4 +/- 1.0 mN/g; p <0.05) and the intact cusp (7.1 +/- 1.9
      mN/g, n = 7, p <0.05). In the radially orientated tissue, responses to endothelin
      1 were similar in all three regions (left: 3.4 +/- 1.0 mN/g; center: 3.2 +/- 0.5
      mN/g; right: 2.3 +/- 0.9 mN/g). CONCLUSION: The contractile ability of valve
      cusps occurs preferentially in the circumferential direction. The enhanced
      contraction of the basal region may have important implications for the
      management of stresses experienced by the hinge of the valve. In addition, these
      findings may be relevant in designing tissue for valve repair by cusp extension
      or for the tissue engineering of a whole valve.

PMID- 15473484
TI  - 3-D simulation of the St. Jude Medical bileaflet valve opening process: fluid
      structure interaction study and experimental validation.
AB  - BACKGROUND AND AIM OF THE STUDY: Simulation of the opening and closure dynamics
      of a mechanical valve through a moving deforming mesh algorithm presents a
      challenge because of the large rotations of the leaflet and of the small gaps
      between the housing and the leaflets, which make remeshing a critical issue. The
      present study offers a computational approach to the simulation of valve leaflet
      motion during the opening process, together with an experimental set-up for
      validation of the model. METHODS: A fully 3-D simulation of the 27 mm St. Jude
      Medical Hemodynamic Plus mechanical valve was performed using the computational
      code, Fluent. Interaction between the leaflet and fluid was simulated through
      customized user subroutines which, according to a weakly coupled approach, update
      the leaflet velocities through subsequent time steps by means of an under
      relaxation procedure. A parallel, experimental test was defined to collect data
      for the set-up of simulations and for validation purposes. RESULTS: The computed
      leaflet velocity and angular displacement compared well with experimental data.
      The model captured the main features of the opening process, and did so also from
      a quantitative viewpoint. Nonetheless, some discrepancies were observed,
      including a delay of approximately 7 ms in the computed leaflet displacement and
      an underestimation by approximately 7% of the maximum computed leaflet velocity.
      CONCLUSION: The weakly coupled approach adopted here limited computational costs,
      thus allowing the simulation of a fully 3-D realistic mechanical valve within 154
      CPU hours at minimal computational costs. No significant drawbacks were raised in
      comparison with the fully coupled approach. The opening process delay was similar
      to that reported previously, and cannot be ascribed to the weakly coupled
      approach adopted here.

PMID- 15473485
TI  - Flow characterization of the ADVANTAGE and St. Jude Medical bileaflet mechanical
      heart valves.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to characterize time-dependent
      flow fields and flow structures within the ADVANTAGE (ADV) and St. Jude Medical
      (SJM) prosthetic bileaflet mechanical heart valves. METHODS: Three-dimensional
      unsteady computational fluid dynamic simulations were conducted in the aortic
      position for both valves. Flow boundary conditions were acquired from an in-vitro
      experiment. The governing equations were solved by a finite volume method that
      employed a moving cell technique to simulate the motion of the valve leaflet in
      the cardiac cycle. The computed velocities were subsequently validated using the
      velocities measured in the in-vitro experiment. RESULTS: Both valves had similar
      flow phenomena at the geometric symmetry plane of the valve housing, and both
      experienced a waterhammer effect upon closure. However, flow characteristics in
      the pivots differed distinctively between both valves. More dynamic flow activity
      was observed at the bi-level butterfly pivots of the ADV valve. Flow vena
      contracta and large flow boundary separation zones at the central flow orifice
      were captured adjacent to the pivots of the SJM valve. During valve opening,
      retrograde systolic flow at the bottom of the pivot was observed. No persistent
      flow stases were seen in the pivots of either valves. CONCLUSION: Although
      overall flow characterization for both valves was similar, flow features within
      each valve's pivots correlated to the pivot design. The bi-level butterfly pivot
      design of the ADV valve appeared to provide relatively easy passages for pivot
      flow washing.

PMID- 15473486
TI  - Doppler assessment of mechanical aortic valve prostheses: effect of valve design
      and size of the aorta.
AB  - BACKGROUND AND AIM OF THE STUDY: Discrepancies between Doppler and catheter
      gradients have been reported for bileaflet aortic valve prostheses. Whether
      modifications in geometric design of newly developed bileaflet valves lead to a
      different Doppler-catheter gradient relationship has not been evaluated. Variable
      results have been reported for tilting-disc prostheses. In addition, the effect
      of aortic size on the Doppler-catheter gradient relationship remains unclear.
      METHODS: Various sizes of On-X and Edwards Mira (identical with Sorin Bicarbon)
      bileaflet valves and Sorin Allcarbon tilting-disc aortic valves (19-25 mm) were
      studied in a pulsatile flow model. Doppler and catheter gradients were measured
      simultaneously. Aortic diameters between 1.8 and 4 cm were evaluated. RESULTS:
      Correlation between Doppler and catheter gradients was excellent (r = 0.98-0.99
      for peak and mean gradients), but in bileaflet valves Doppler significantly
      overestimated the corresponding catheter gradients as reflected by slopes of the
      regression lines (1.57-1.8). In the range of relevant gradients > or = 10 mmHg,
      Doppler exceeded catheter gradients by 40 +/- 17% (peak) and 39 +/- 16% (mean) in
      Mira valves, and by 46 +/- 19% (peak) and 43 +/- 14% (mean) in On-X valves. In
      the Sorin tilting-disc valve, Doppler accurately reflected catheter gradients
      (slopes of regression lines 1.05-1.14). The aortic diameter significantly
      influenced results in only tilting-disc valves, but in absolute terms the effect
      was clinically less relevant. CONCLUSION: Discrepancies between Doppler and
      catheter gradients are common to all bileaflet valves, regardless of their
      specific geometric design, whereas tilting-disc valves must be considered
      individually. The influence of aortic size on the Doppler-catheter gradient
      relationship appears clinically to be less relevant in prosthetic valves.

PMID- 15473487
TI  - Prototype anionic detergent technique used to decellularize allograft valve
      conduits evaluated in the right ventricular outflow tract in sheep.
AB  - BACKGROUND AND AIM OF THE STUDY: Biodegradable polymeric materials or
      extracellular matrix scaffolds are used in tissue-engineered heart valve designs,
      with the expectation of replicating the anatomic, histological and biomechanical
      characteristics of semi-lunar valves. The study aim was to evaluate the extent of
      in-vivo recellularization and the explant pathology findings of a prototype
      anionic, non-denaturing detergent and endonuclease technique used to
      decellularize allograft (homograft) valve conduits implanted in the right
      ventricular outflow tract (RVOT) of sheep, and to identify possible risks
      associated with tissue-engineered heart valve conduits based on decellularized
      allograft semilunar valve scaffolds. METHODS: Valve conduits were decellularized
      using a solution of N-lauroylsarcosinate and endonucleases, rinsed in lactated
      Ringers solution, and stored in an antibiotic solution at 4 degrees C until
      implanted. Explanted valves and unimplanted controls were examined
      macroscopically, radiographically (for calcification) and histologically using
      immunohistochemistry (IHC), routine and special histological stains, transmission
      electron microscopy (TEM) and polarized light microscopy (evaluation of collagen
      crimp). RESULTS: Cells and cellular remnants were uniformly absent in the
      decellularized cusps, but occasional focal sites of arterial wall smooth muscle
      cells and to a greater extent subvalvular cardiac myocytes were variably
      retained. The trilaminar histological structure of the cusp was preserved. Valve
      conduit-related pathology consisted of intracuspal hematoma formation, collagen
      fraying, thinning of the conduit wall, and inflammatory cells associated with
      cardiac myocyte remnants. Cuspal calcification was not seen, but elastic fibers
      in the conduit wall and retained subvalvular cardiac myocyte remnants were liable
      to calcification. Fibrous sheath formation was present on the luminal surface of
      the conduit and extended over the cuspal surfaces to a variable extent.
      Myofibroblast-like cells repopulated the conduit wall and the basal region of the
      cusp. Re-endothelialization was variably present on the cuspal surfaces.
      CONCLUSION: Explant pathology findings showed that in-vivo recellularization
      occurred, but was focally limited to regions of the arterial wall and cusp base.
      Safety concerns related to detergent and endonuclease use were identified.
      Methods to eliminate the potential for structural deterioration and enhance the
      rate and extent of recellularization of valve conduit tissue are required.
      Pathology findings showed implantation of valve conduits in the RVOT of juvenile
      sheep for 20 weeks to be a reliable animal model for the initial in-vivo
      assessment of decellularized valves. A 20-week period may be insufficient however
      to evaluate the long-term safety and effectiveness of a tissue-engineered valve
      conduit, as these depend on effective and phenotypically appropriate
      recellularization accompanied by sustained cell viability and function.

PMID- 15473488
TI  - Dynamic and reversible changes of interstitial cell phenotype during remodeling
      of cardiac valves.
AB  - BACKGROUND AND AIM OF THE STUDY: The roles of cardiac valvular interstitial cells
      (VIC) in extracellular matrix remodeling in fetal development, adaptation and
      response to injury are largely unknown. METHODS: The phenotype of VIC was studied
      in health (normal adult human and sheep), development (fetal human and sheep),
      disease (human mitral valves with myxomatous degeneration), adaptation (clinical
      pulmonary to aortic valve autografts) and tissue-engineered heart valves matured
      in vitro and remodeled in vivo. Cell phenotype was assessed using expression of
      vimentin (V), alpha-smooth muscle actin (SMA, A), matrix metalloproteinase (MMP)
      13/collagenase-3 (M), and SMemb (S). RESULTS: VIC in normal adult valves were
      predominantly quiescent fibroblasts immunoreactive to vimentin (89.7 +/- 2.5%),
      but not MMP-13 or SMemb, with only 2.5 +/- 0.4% of alpha-SMA-positive cells
      ('normal/quiescent' phenotype: V+/A-/M-/S-). In contrast, fetal VIC were mostly
      activated myofibroblasts ('developing/activated' phenotype: V+/A+/M+/S+), with
      62.1 +/- 5.0% of cells staining positive for alpha-SMA. VIC in myxomatous valves,
      short-term autografts and engineered valves in vitro were also activated
      myofibroblasts with coexpression of vimentin, alpha-SMA (36.2 +/- 3.7%, 19.3 +/-
      2.4%, and 60.3 +/- 9% positive cells, respectively), strong MMP-13 activity
      indicative of collagen remodeling, and SMemb ('remodeling/activated' phenotype:
      V+/A+/M+/S+). In contrast, VIC in long-term pulmonary autografts and engineered
      valve explants had a mostly fibroblast-like phenotype, with sparse alpha-SMA
      expression (6.0 +/- 1% and 5.4 +/- 1.0% positive cells) (V+/A-/M-/S-).
      CONCLUSION: Most VIC in normal valves were quiescent with a fibroblast-like
      phenotype. VIC in developing, diseased, adapting and engineered valves adjust to
      a dynamic environment through VIC activation and secretion of proteolytic enzymes
      mediating extracellular matrix remodeling ('developing/ remodeling/activated'
      phenotype), followed by a normalization of phenotype.

PMID- 15473489
TI  - Beta-actin cannot be used as a control for gene expression in ovine interstitial
      cells derived from heart valves.
AB  - BACKGROUND AND AIM OF THE STUDY: In gene expression studies, endogenous controls
      that are constitutively expressed (housekeeping genes) are commonly used to
      normalize for variations in cDNA synthesis efficiency. In the present study, a
      frequently used control gene, beta-actin, was examined in ovine heart valves to
      evaluate its applicability as a housekeeping gene for this tissue. METHODS:
      Interstitial cells (IC) of the four heart valves were isolated using the
      outgrowth explant method. Cells were cultured under different serum conditions
      (10% or 20% fetal bovine serum or 20% sheep serum) up to passage (P) 5. mRNA from
      fresh tissue and from cells at P0 and P5 was isolated, and expression of beta
      actin determined using reverse transcription-polymerase chain reaction (RT-PCR).
      An identical control sample was used for each PCR and each gel electrophoresis.
      Data were expressed as a relative value of this control sample. RESULTS: beta
      Actin expression in the aortic valve was significantly lower than in other
      valves. The mRNA level of beta-actin was four-fold lower in freshly isolated IC
      than in cultured IC. Once up-regulated by in-vitro culturing conditions, beta
      actin expression did not change from P0 to P5. An important increase in the
      variation of beta-actin expression was observed in cultured cells as compared to
      fresh cells. Different serum conditions did not lead to different beta-actin
      levels. CONCLUSION: Due to the variation in expression, beta-actin cannot be used
      as a reference for gene expression of ovine-derived heart valve IC in culture.

PMID- 15473490
TI  - Body piercing: a rare cause of mitral valve endocarditis.
AB  - Body piercing has become a way of life for many individuals. It represents
      freedom, as well as rebellion, and can provide shock value to the public. Often,
      it is used as a rite of passage from adolescence into adulthood, and can also
      provide a boost in self-esteem. However, body piercing may lead to non-infectious
      complications such as prolonged bleeding and keloid formation, while infectious
      complications include the transmission of blood-borne infections (e.g. human
      immunodeficiency virus, hepatitis B, C and D), as well as bacteremia through the
      site of piercing. Infective endocarditis in individuals with congenital heart
      defects has been identified after body piercing. Here, the first documented case
      is reported of mitral valve endocarditis in a previously fit and healthy young
      female following navel piercing.

PMID- 15473491
TI  - Aortic valve rupture due to high-voltage electrical injury: case report.
AB  - In the heart, the most common sequelae after electrical injury are myocardial
      contusion and arrhythmias. A case is presented of segmental ventricular
      dysfunction and severe aortic regurgitation due to laceration of the right
      coronary cusp of the aortic valve caused by electrical injury. To the authors'
      knowledge, this is the first reported case of valvular rupture due to electrical
      injury.

PMID- 15473492
TI  - Aortic valve regurgitation in alkaptonuria.
AB  - Aortic valve lesions associated with alkaptonuria tend mostly to be due to aortic
      valve stenosis, while aortic valve regurgitation is only rarely observed. Herein,
      a case is reported of severe aortic valve regurgitation and a fibrous strand in a
      patient with alkaptonuria. A 65-year-old male, with a history of inferior
      myocardial infarction, presented with symptoms of congestive heart failure.
      Alkaptonuria was diagnosed based on urine coloration, skin pigmentation and
      ochronotic arthropathy in the vertebrae and hip. Grade IV aortic valve
      regurgitation with mild aortic valve stenosis and occlusive disease in the right
      coronary artery indicated a need for aortic valve replacement and coronary artery
      bypass grafting. Sclerotic change in the cusps, and shrinkage of the non-coronary
      cusp, impeded normal coaptation of the aortic valve, and the left-coronary cusp
      also had a fibrous strand suspending the free margin of the cusp from the aortic
      wall just above the commissure. The sclerotic change in the cusps, and shrinkage
      of the non-coronary cusp, appeared to be the causative lesion of aortic valve
      regurgitation, implying that cardiovascular ochronosis may cause aortic valve
      regurgitation.

PMID- 15473493
TI  - Hutchinson-Gilford progeria syndrome with severe calcific aortic valve stenosis
      and calcific mitral valve.
AB  - The case of a 12-year-old girl with clinical features of progeria with severe
      calcific valvar aortic stenosis is presented. The mitral valve showed the
      presence of calcium, and peripheral vascular disease was also present, though
      there was no family history of this. Aortic valve replacement was deferred
      because of insufficient data relating to this condition. The genetics and
      phenotypic mechanisms of the disease are reviewed. In view of the association of
      progeria with valve disease, all patients should undergo electrocardiography and
      echocardiography as part of their routine work-up.

PMID- 15473494
TI  - In response to Stalenhoef JE,, Mellema EC, Veeger NJ, Ebels T. Thrombogenicity
      and reoperation of the St. Jude Medical valve: a comparison with the conventional
      St. Jude valve. J Heart Valve Dis 2003; 12: 635-639.

PMID- 15473495
TI  - In response to Bohm JO et al. Hemodynamic performance following the Ross
      operation: comparison of two different techniques. J Heart Valve Dis 2004; 13:
      174-180.

PMID- 15473496
TI  - Quantitative assessment of changes in patients' constructs of quality of life: an
      application of multilevel models.
AB  - It has often been proposed that quality of life (QL) instruments should account
      for potentially changing conceptualisations of QL as patients adapt to disease
      (response-shift). Most instruments do not do this, and some that do are
      relatively complicated and burdensome for patients. The extent to which patients
      reconceptualise QL is unknown, and it is unclear whether this additional
      complication is necessary. This paper reviews existing methods for assessing
      response-shift and introduces an alternative approach using multilevel models.
      The method is described using data from a cancer clinical trial, and its
      performance is evaluated in simulations. The models reveal substantial response
      shift in these cancer patients. Simulations under the null hypothesis of zero
      response-shift confirm that the method performs correctly in terms of its risk of
      type I error, and further simulations illustrate its statistical power to detect
      pre-defined levels of response-shift. The method is a relatively simple extension
      of familiar multiple regression models and yields parameters with a simple
      interpretation, representing the changes in importance of QL domains over time.
      It can be applied to existing datasets collected with other analysis strategies
      in mind and may have application in the investigation of response shifts and
      other manifestations of adaptation.

PMID- 15473497
TI  - Health related quality of life: a changing construct?
AB  - In 186 patients with early colon cancer, we investigated the assumption that the
      meaning of 'quality of life' (QL) remains constant over time. Within a phase-III
      trial (SAKK 40/93), patients estimated both their overall QL and a range of
      disease- and treatment-related domains at five timepoints, comprising three
      concurrent and 2 retrospective estimates: their pre-surgery QL both before
      surgery and retrospectively thereafter, and their pre-adjuvant QL both at the
      beginning of adjuvant treatment and retrospectively about 2 months later, and
      their current QL 2 weeks thereafter. Multilevel models were developed to
      determine whether the selected domains made stable contributions to overall QL at
      the concurrent estimates. The weights of the domains changed over time. They did
      not differ significantly according to whether patients were considering their
      concurrent state or reflecting on this state at a later timepoint. In the process
      of adaptation, patients with early colon cancer substantially change the relative
      importance of QL domains to overall QL. This finding argues for QL as a changing
      construct and against the assumption that domain-specific weights are stable
      across distinct clinical phases.

PMID- 15473498
TI  - Electronic diaries and questionnaires: designing user interfaces that are easy
      for all patients to use.
AB  - We propose a set of requirements for designing handheld computer systems for
      electronic collection of patient diary and questionnaire data in clinical trials:
      (1) the system should be suitable for use by all types of patient to be included
      in the clinical trial programme; (2) patients must be capable of using the system
      and be comfortable with it after a short period of training; (3) responses should
      always result from an action by the user--defaults should not be taken as data;
      (4) all information necessary to a given question should be simultaneously
      available on the screen. This applies to both the questions and the response
      options. We present guidelines as to how these requirements may be met in
      practice, so that bias may be avoided both in patient selection and in the
      responses made; so that electronic data collection may be as effective as
      possible, and so that study procedures are convenient and unobtrusive for the
      patients.

PMID- 15473499
TI  - Baseline FACT-G score is a predictor of survival for advanced lung cancer.
AB  - The objective of this study is to evaluate whether patient-reported baseline
      health-related quality of life (HRQL) measured by the Functional Assessment of
      Cancer Therapy-General (FACT-G) instrument is predictive of survival for patients
      with advanced lung cancer. METHODS: Consecutive patients with advanced lung
      cancer planning to undergo palliative chemotherapy in the outpatient clinics of a
      Canadian tertiary care cancer centre were enrolled on study. FACT-G total scores
      and clinical predictors of survival (age, sex, histology, stage of disease,
      previous weight loss, presence of liver metastases and performance status) were
      prospectively collected at baseline. Survival data was subsequently collected
      retrospectively from the Alberta Cancer Registry. Stratified Cox Proportional
      Hazards analysis was done examining the influence of baseline total FACT-G scores
      on survival, controlling for potential clinical confounders. RESULTS: Median
      survival of the 42 patient cohort was 9.9 months with a 2-year survival of 16.7%.
      Multivariate analysis indicated that baseline FACT-G total score is significantly
      associated with survival (p = 0.004). CONCLUSION: Baseline HRQL is a
      statistically significant predictor of survival for patients with advanced lung
      cancer. When used along with traditional clinical factors, patient-reported
      baseline HRQL assessment using the FACT-G provides additional prognostic
      information to the patient and clinician.

PMID- 15473500
TI  - Order effects in the assessment of quality of life in cancer patients.
AB  - Methodological studies and outcome research often include several health-related
      quality of life (HRQoL) measurement scales in one questionnaire. Psychological
      studies have previously demonstrated that changing the sequential order of
      measurement scales within a questionnaire can alter the pattern of responses.
      Little is known, however, about whether there are order effects on the assessment
      of HRQoL in cancer patients. Here we address this issue in a study of 190
      Singaporean cancer patients who were assessed using two different HRQoL
      instruments placed in alternating sequence within a questionnaire package.
      Measurement properties of the instruments, including the number of missing
      values, means, variability, known-group validity and internal consistency, were
      compared in the two samples representing different presentation orders. The HRQoL
      instruments administered in different sequential orders appeared to be equivalent
      in several aspects. No major effect of presentation order on outcomes was shown.
      The reasons and implications of the absence of an order effect are discussed. We
      conclude that presentation order is unlikely to alter the responses to the two
      HRQoL instruments.

PMID- 15473501
TI  - Validation of the cancer needs questionnaire (CNQ) short-form version in an
      ambulatory cancer setting.
AB  - The short-form Cancer Needs Questionnaire (CNQ) is a self-administered cancer
      specific questionnaire designed to assess patients' needs across several domains.
      The purpose of this study is to further evaluate its internal consistency and
      construct validity, in a group of ambulatory patients with cancer. Four hundred
      and fifty patients with a variety of cancer types participated. Factor analysis
      reproduced five domains: psychological; health information; physical and daily
      living; patient care and support; and interpersonal communication needs.
      Cronbach's alpha coefficients ranged from 0.94 to 0.77, indicating substantial
      consistency across items grouped in the five domains. A priori predictions
      regarding convergent and contrasting groups construct validity were explored
      using bivariate relationships between domains of the short-form CNQ, the EORTC
      QLQC-30 and Beck Depression Inventory (short-form), with support provided for
      most of the predictions. The current study provides supportive evidence that the
      short-form CNQ is a reliable and valid instrument for assessing the needs of
      patients with cancer in an ambulatory care setting.

PMID- 15473502
TI  - The relationship of changes in EORTC QLQ-C30 scores to ratings on the Subjective
      Significance Questionnaire in men with localized prostate cancer.
AB  - PURPOSE: To examine the relationship between changes in health-related quality-of
      life (HRQOL) on the EORTC Quality of Life Questionnaire (QLQ-C30), and patients'
      perceptions of HRQOL changes as measured by the Subjective Significance
      Questionnaire (SSQ). PATIENTS AND METHODS: A total of 101 patients completed the
      QLQ-C30 on weeks 1, 4 and 7 of radical external-beam radiation therapy (RT) for
      localized cancer of the prostate. Patients rated their change in physical
      functioning, emotional functioning, social functioning, and overall/global
      quality of life (QOL) by completing a seven-category SSQ at weeks 4 and 7. The
      association between changes in the QLQ-C30 change and the corresponding SSQ
      ratings were determined by calculation of mean change scores for each SSQ
      category and by Spearman rank correlation coefficient analysis. RESULTS:
      Patients' completion of the QLQ-C30 and SSQ exceeded 95%. Statistically
      significant changes in fatigue, pain, appetite, diarrhea, and global QOL scores
      were detected during RT. For patients reporting 'a little' change in global QOL
      on the SSQ, absolute mean QLQ-C30 change scores ranged between 0 to 15 points
      with 12/16 mean change scores between 2.5 and 8.5 points. In the entire study
      sample, correlations between SSQ patient ratings and QLQ-C30 change scores were
      lower than previously reported, ranging between 0.15 and 0.24 for the four
      different domains, but were higher when QOL scores producing ceiling effects were
      omitted. CONCLUSION: The SSQ and QLQ-C30 may measure related concepts that could
      assist in the interpretation of changes in scores and in the calibration of the
      QLQ-C30. However, the nature of this relationship could not be elucidated in this
      data set because of a lack of variance in HRQOL scores in the study sample.
      Further investigation should be carried out in study samples with sufficient
      variance to allow more robust conclusions.

PMID- 15473503
TI  - Responsiveness of the generic EQ-5D summary measure compared to the disease
      specific EORTC QLQ C-30.
AB  - INTRODUCTION: We investigated whether the sensitivity of the generic health
      related quality of life (HRQoL) EQ-5D summary measure (or index) to detect
      changes over time in a clinical setting is comparable with that of a disease
      specific HRQoL questionnaire. METHODS: Patients with liver metastases (n = 75)
      filled out the five domains of the EQ-5D self-classifier, the EQ VAS, and the
      EORTC QLQ C-30 (a disease-specific (cancer) HRQoL questionnaire). The HRQoL
      instruments were completed before intervention, and 1/2 month and 3 and 6 months
      after intervention. Three analyses were performed. First, the EQ-5D index (based
      on self-classification) was compared to the EQ VAS. Second, the EQ-5D domains
      were compared to corresponding EORTC QLQ C-30 scales. Third, EQ-5D index and EQ
      VAS were compared with the EORTC QLQ C-30 global health-status scale. Effect size
      was chosen as the metric of responsiveness. RESULTS: The EQ-5D index was slightly
      less responsive than the EQ VAS. Overall, the responsiveness of the EQ-SD index
      and EQ VAS was equal to the EORTC QLQ C-30 global health-status scale.
      CONCLUSION: Despite its generic principle and the apparent crudeness of its
      framework, the responsiveness of the EQ-5D proved to be comparable to that of a
      disease-specific HRQoL questionnaire in this specific clinical setting.

PMID- 15473504
TI  - Using the effect size to model change in preference values from descriptive
      health status.
AB  - OBJECTIVES: This pilot study describes a modelling approach to translate group
      level changes in health status into changes in preference values, by using the
      effect size (ES) to summarize group-level improvement. METHODS: ESs are the
      standardized mean difference between treatment groups in standard deviation (SD)
      units. Vignettes depicting varying severity in SD decrements on the SF-12 mental
      health summary scale, with corresponding symptom severity profiles, were valued
      by a convenience sample of general practitioners (n = 42) using the rating scale
      (RS) and time trade-off methods. Translation factors between ES differences and
      change in preference value were developed for five mental disorders, such that ES
      from published meta-analyses could be transformed into predicted changes in
      preference values. RESULTS: An ES difference in health status was associated with
      an average 0.171-0.204 difference in preference value using the RS, and 0.104
      0.158 using the time trade off. CONCLUSIONS: This observed relationship may be
      particular to the specific versions of the measures employed in the present
      study. With further development using different raters and preference measures,
      this approach may expand the evidence base available for modelling preference
      change for economic analyses from existing data.

PMID- 15473505
TI  - Understanding health state valuations: a qualitative analysis of respondents'
      comments.
AB  - Self-completed questionnaires (usually distributed by post) and visual analogue
      scales (VAS) are common means for collecting valuations for hypothetical EQ-5D
      health states. Although opportunities for respondents to comment on aspects of
      the exercise are often included, these data have rarely been the focus of
      analyses. This paper, therefore, reports on solicited and unsolicited written
      comments received in a New Zealand survey in 1999 to which 1360 people responded
      of whom approximately 50% made comments. The comments were systematically
      analysed via an inductive process that allowed principal themes to emerge with
      respect to understanding the peculiarities of respondents' valuations,
      particularly common 'data problems', and their perceptions as to the adequacy or
      otherwise of the EQ-5D classification system. From our findings we conclude that
      the valuation exercise imposes a substantial cognitive burden on respondents and
      many do not understand it (for a variety of reasons documented in the paper).
      Also, although there is some evidence for expanding the EQ-5D (generic) health
      related quality of life dimensions, more research as to whether this holds for a
      larger sample and across cultural settings is needed. We offer recommendations
      for future research into understanding respondents' cognitive processes and
      possible revisions to the design and administration of the EQ-5D.

PMID- 15473506
TI  - Acceptability of the Schedule for the Evaluation of Individual Quality of Life
      Direct Weight (SEIQoL-DW) in youth with type 1 diabetes.
AB  - The purpose of this study was to assess the acceptability of the Schedule for the
      Evaluation of Individual Quality of Life-Direct Weight (SEIQoL-DW) in youth with
      diabetes. This measure asks respondents to assess the importance and satisfaction
      of domains that they nominate as being important to their own quality of life.
      Seventy-seven young people (age 8-17 years, M = 12.4) with type 1 diabetes were
      given the SEIQoL-DW. Data from 10 participants were deemed invalid due to
      respondents' inability to understand the task. Respondents whose data were deemed
      invalid were all under 12 years of age, M = 9.3. For participants with valid
      data, interviewers' ratings of participant boredom and fatigue were low. Time to
      complete the interview was reasonably short, M = 14.9 min. Of the 335 total QOL
      domains nominated by participants with valid data, only 19 domains (6%) were
      nominated with the assistance of a standard list. Forty-five participants
      nominated 'diabetes' as a life domain. Results indicate the SEIQoL-DW performed
      well with respondents over 12 years of age, is appropriate for samples with
      diabetes, and taps into diabetes-relevant domains. Further research with more
      diverse samples is needed before firm age cut-offs can be established for its
      use.

PMID- 15473507
TI  - A test of the reliability and validity of a diabetes specific quality of life
      scale in a Nigerian hospital.
AB  - The purpose of this study was to test the reliability of the Well-being and
      Diabetes Treatment Satisfaction Questionnaires among clinic patients with type 2
      diabetes as well as determine the clinical correlates of these measures. A cross
      sectional survey was conducted using the Well-being Questionnaire and the
      Diabetes Treatment Satisfaction Questionnaire. Other demographic and clinical
      indices of age, sex, body mass index, disease duration and blood glucose levels
      were also recorded. 83 responses were analysed. Subjects were aged between 25 and
      75 years, mean 55.5+/-11.1 years. 50.6% were males while 49.4% were females. Mean
      diabetes duration was 4.9+/-6.5 years. 67 (80.7%) were receiving oral agents and
      dietary modification while 16 (19.3%) were on insulin therapy. The internal
      consistency for responses to the well-being subscales and treatment satisfaction
      scale produced satisfactory alpha coefficients ranging from 0.73 to 0.88 and 0.74
      respectively. Inter-item correlations were ranged between 0.19 and 0.45 for
      depression subscale; 0.22-0.78 for anxiety subscale; 0.33-0.58 for energy
      subscale; 0.33-0.79 for positive well-being subscale; and -0.22 to 0.79 for the
      treatment satisfaction scale. Item-total correlations ranged between 0.39 and
      0.87 across the two scales: well-being (0.59-0.87) and treatment satisfaction
      (0.39-0.78). Mean scale scores were similar in both insulin and oral
      hypoglycaemic drug treated patients. Positive well-being was higher in males
      13.4+/-4.1 vs. 11.5+/-4.3 in females p = 0.04. None of the well-being subscale
      scores, or treatment satisfaction correlated with age, disease duration, body
      mass index or glycaemic control. The well-being and treatment satisfaction scales
      are reliable instruments for the measurement of diabetes specific quality of life
      and treatment satisfaction in Nigerians although they were originally designed
      and developed among a UK population. It is hoped that our data would provide the
      basis for future comparisons and improving diabetes care.

PMID- 15473508
TI  - How well do parents know their children? Implications for proxy reporting of
      child health-related quality of life.
AB  - OBJECTIVES: This study examined parental knowledge of their children's oral
      health-related quality of life (OHRQoL) (Objective 1), and the effects of
      different analytical techniques to manage 'Don't know' (DK) responses on the
      validity and reliability of the questionnaire (Objective 2) and the level of
      agreement between parental and child reports (Objective 3). METHODS: The parental
      (PPQ) and child (CPQ11-14) components of the Child Oral Health Quality of Life
      Questionnaire were used. Objectives 1 and 2 were addressed in the study that
      involved 221 parents and Objective 3 in the study that involved 63 pairs of
      parents and children. Four methods for treating DK responses in the PPQ were
      tested: listwise deletion, item mean imputation, imputation of the value zero and
      adjustment of scores to account for items with DK responses. RESULTS:
      Respectively, 26 and 11% of the parents gave > or = 3 and 6 > or = DK responses
      to 33 items comprising the PPQ. DK responses were associated with child's age and
      clinical condition, and parental gender. The methods of managing DK responses did
      not have differing effects on the measurement properties of the PPQ and the level
      of agreement between parents and children. CONCLUSION: Some parents have limited
      knowledge concerning their children's OHRQoL. However, given that parental and
      child reports are measuring different realities, information provided by parents
      is useful even if it is incomplete.

PMID- 15473509
TI  - Health-related quality of life of children and adolescents with chronic illness-
      a two year prospective study.
AB  - The aim of this study was to compare the self-reported health-related quality of
      life (HRQL) of children and adolescents with diabetes, asthma or cystic fibrosis
      (CF) with the HRQL of a large community sample, to assess the extent to which the
      HRQL of the children and adolescents with chronic illness changes over time, and
      to examine the consistency of changes in different HRQL domains. One hundred and
      twenty three young people aged 10-16 years with asthma, diabetes, or CF were
      recruited from specialist paediatric clinics. Children rated their HRQL using the
      Child Health Questionnaire (CHQ) and three disease-specific measures at baseline,
      6, 12, 18 and 24 months post-baseline. In several areas, the HRQL of children
      with chronic illness was significantly worse than that of children in the
      community sample. Over the 2 years of the study, although children with asthma
      and diabetes did not report significant changes in CHQ scores rating their
      physical health, they reported significant improvements in scores rating the
      extent to which health problems interfered with physical and family activities.
      CHQ scores describing their physical health reported by children with CF declined
      significantly but there was no significant change in scores rating interference
      with physical and family activities.

PMID- 15473510
TI  - The development and psychometric evaluation of the Motivation and Energy
      Inventory (MEI).
AB  - Because depressed patients commonly experience reductions in motivation and
      energy, both as symptoms of their disorder and as side effects of
      pharmacotherapy, it is important to identify interventions that can restore their
      vitality. The Motivation and Energy Inventory (MEI) was recently developed to
      facilitate the evaluation of such efforts both in depression research, as well as
      in other therapeutic areas where vitality is an important issue. The constructs
      addressed by the MEI were identified through a combination of literature review,
      consultation with experts, and patient focus groups. Potential problems
      identified during cognitive testing and addressed in subsequent revisions related
      to the instructions, reference period, response scale sizes, and response scale
      labels, as well as a number of item-specific issues. Most recently, the data from
      two randomized, placebo-controlled clinical trials were utilized to evaluate the
      psychometric properties of the new questionnaire. In general, the data collected
      during the first and second trial were used for exploratory and confirmatory
      analysis, respectively. Consistent with the measurement model of the MEI, the
      psychometric results confirm that the instrument has three factors generally
      addressing physical energy, mental energy, and social motivation. Furthermore,
      these results provide evidence for the internal consistency, construct validity,
      and responsiveness of all three MEI subscales. Additional work is currently
      underway to examine test-retest reliability and establish minimal clinically
      important difference values for the MEI subscales.

PMID- 15473512
TI  - Patterns of healthcare use for diarrhoea at sites in six countries.

PMID- 15473511
TI  - Exploring the influence of depressive symptoms on physical disability: a cohort
      study of elderly in Beijing, China.
AB  - OBJECTIVES: This study examined the influence of depressive symptoms on the
      prevalence of physical disability in a cohort study of Beijing elderly (1992-
      2000) and analyses the role of some confounding variables in this relationship.
      METHODS: A cohort of 1828 elderly aged 55 and older who were initially free of
      any physical disability was followed up for 8 years. Baseline depression was
      assessed by the Center for Epidemiological Studies Depression Scale. Disability
      on activities of daily living (BADL and IADL) was measured in 1994, 1997, and
      2000 respectively. RESULTS: The cumulative percentages of persons who developed
      BADL disability and IADL disability during each follow-up interview was
      significantly greater among depressed than non-depressed individuals. Compare
      with the 1525 non-depressed individuals, the 303 depressed individuals had a
      relative risk (95% confidence interval) of 2.52 (2.02, 4.82) for BADL disability
      and 4.98 (2.46, 10.09) for IADL disability, respectively. Although adjustment for
      confounding factors reduced the risk to 2.20 (1.33, 3.62) and 4.29 (2.08, 8.86),
      the detrimental effect of depression on disability remained significant. The
      items of IADL which connected physical activity had higher impairment among
      depressed individuals. CONCLUSIONS: Depression in elderly persons may increase
      the risk for prevalent disability. It is very important for elders to prevent and
      reduce depression for improving the quality of their life and physical function.

PMID- 15473513
TI  - A community-based cluster survey on preferences for treatment of diarrhoea and
      dysentery in Zhengding county, Hebei province, China.
AB  - Passive surveillance on the burden of disease due to diarrhoea will underestimate
      the burden if families use healthcare providers outside the surveillance system.
      To study this issue, a community-based cluster survey was conducted during
      October 2001 in the catchment area for a passive surveillance study in Zhengding
      county, a rural area of northern China. Interviews were conducted at 7 randomly
      selected households in each of 39 study villages. The respondents indicated where
      they sought initial care for cases of diarrhoea or dysentery among children or
      adults. In the absence of diarrhoea and dysentery cases in the household in the
      preceding four weeks, the respondents were asked about healthcare use for a
      hypothetical case. Overall, 80% (95% confidence interval [CI] 67-93%) would chose
      the village clinic, 11% village pharmacy (95% CI 1-22%), 4% township hospital
      (95% CI -1-10%), 4% self-treatment (95% CI 1-8%), and 1% county hospital (95% CI
      0-2%). Approximately, 84% of patients would seek treatment for diarrhoea and
      dysentery at centres participating in passive surveillance, suggesting that
      passive surveillance will provide a relatively accurate assessment of burden of
      diarrhoea in Zhengding county.

PMID- 15473514
TI  - Preferences for treatment of diarrhoea and dysentery in Kaengkhoi district,
      Saraburi province, Thailand.
AB  - To estimate the proportion of cases missed in a passive surveillance study of
      diarrhoea and dysentery at health centres and hospitals in Kaengkhoi district,
      Saraburi province, Thailand, a community-based cluster survey of treatment
      seeking behaviours was conducted during 21-23 June 2002. Interviews were
      conducted at 224 households among a study population of 78,744. The respondents
      reported where they sought care for diarrhoea and dysentery in children aged less
      than five years and adults aged over 15 years. Health centres or hospitals were
      the first treatment choice for 78% of children with dysentery (95% confidence
      interval [CI] 63-94%), 64% of children with diarrhoea (95% CI 54-74%), 61% of
      adults with dysentery (95% CI 40-82%), and 35% of adults with diarrhoea (95% CI
      17-54%). A high degree of heterogeneity in responses resulted in a relatively
      large design effect (D=3.9) and poor intra-cluster correlation (rho=0.3). The
      community survey suggests that passive surveillance estimates of disease
      incidence will need to be interpreted with caution, since this method will miss
      nearly a quarter of dysentery cases in children and nearly two-thirds of
      diarrhoea cases in adults.

PMID- 15473515
TI  - Diarrhoea episodes and treatment-seeking behaviour in a slum area of North
      Jakarta, Indonesia.
AB  - Visits to household during a census in an impoverished area of north Jakarta were
      used for exploring the four-week prevalence of diarrhoea, factors associated with
      episodes of diarrhoea, and the patterns of healthcare use. For 160,261 urban slum
      dwellers, information was collected on the socioeconomic status of the household
      and on diarrhoea episodes of individual household residents in the preceding four
      weeks. In households with a reported case of diarrhoea, the household head was
      asked which form of healthcare was used first. In total, 8,074 individuals (5%)-
      13% of children aged less than five years and 4% of adults--had a diarrhoea
      episode in the preceding four weeks. The two strongest factors associated with a
      history of diarrhoea were a diarrhoea episode in another household member in the
      four weeks preceding the interview (adjusted odds ratio [OR] 11.1; 95% confidence
      interval [CI] 10.4-11.8) and age less than five years (adjusted OR 3.4; 95% CI
      3.2-3.5). Of the 8,074 diarrhoea cases, 1,969 (25%) treated themselves, 1,822
      (23%) visited a public-health centre (PHC), 1,462 (18%) visited a private
      practitioner or a private clinic, 1,318 (16%) presented at a hospital, 753 (9%)
      bought drugs from a drug vendor, and 750 (9%) used other healthcare providers,
      such as belian (traditional healers). Children with diarrhoea were most often
      brought to a PHC, a private clinic, or a hospital for treatment. Compared to
      children, adults with diarrhoea were more likely to treat themselves. Individuals
      from households in the lowest-income group were significantly more likely to
      attend a PHC for treatment of diarrhoea compared to individuals from households
      in the middle- and higher-income groups.

PMID- 15473516
TI  - Factors associated with reported diarrhoea episodes and treatment-seeking in an
      urban slum of Kolkata, India.
AB  - In an urban slum in eastern Kolkata, India, reported diarrhoea rates, healthcare
      use patterns, and factors associated with reported diarrhoea episodes were
      studied as a part of a diarrhoea-surveillance project. Data were collected
      through a structured interview during a census and healthcare-use survey of an
      urban slum population in Kolkata. Several variables were analyzed, including (a)
      individual demographics, such as age and educational level, (b) household
      characteristics, such as number of household members, religious affiliation of
      the household head, building material, expenditure, water supply and sanitation,
      and (c) behaviour, such as hand-washing after defecation and healthcare use. Of
      57,099 study subjects, 428 (0.7%) reported a diarrhoea episode sometime during
      the four weeks preceding the interview. The strongest independent factors for
      reporting a history of diarrhoea were having another household member with
      diarrhoea (adjusted odds ratio [OR]=3.8; 95% confidence interval [CI] 3.3-4.4)
      and age less than 60 months (adjusted OR=3.7; 95% CI 3.0-4.7). The first choice
      of treatment by the 428 subjects was as follows: 151 (35%) had self- or parent
      treatment, 150 (35%) consulted a private allopathic practitioner, 70 (16%) went
      directly to a pharmacy, 29 (7%) visited a hospital, 14 (3%) a homoeopathic
      practitioner, 2 (0.5%) an ayurvedic practitioner, and 12 (3%) other traditional
      healers. The choices varied significantly with the age of patients and their
      religion. The findings increase the understanding of the factors and healthcare
      use patterns associated with diarrhoea episodes and may assist in developing
      public-health messages and infrastructure in Kolkata.

PMID- 15473517
TI  - Healthcare use for diarrhoea and dysentery in actual and hypothetical cases, Nha
      Trang, Viet Nam.
AB  - To better understand healthcare use for diarrhoea and dysentery in Nha Trang,
      Viet Nam, qualitative interviews with community residents and dysentery case
      studies were conducted. Findings were supplemented by a quantitative survey which
      asked respondents which healthcare provider their household members would use for
      diarrhoea or dysentery. A clear pattern of healthcare-seeking behaviours among
      433 respondents emerged. More than half of the respondents self-treated
      initially. Medication for initial treatment was purchased from a pharmacy or with
      medication stored at home. Traditional home treatments were also widely used. If
      no improvement occurred or the symptoms were perceived to be severe, individuals
      would visit a healthcare facility. Private medical practitioners are playing a
      steadily increasing role in the Vietnamese healthcare system. Less than a quarter
      of diarrhoea patients initially used government healthcare providers at commune
      health centres, polyclinics, and hospitals, which are the only sources of data
      for routine public-health statistics. Given these healthcare-use patterns,
      reported rates could significantly underestimate the real disease burden of
      dysentery and diarrhoea.

PMID- 15473518
TI  - Acceptability and accessibility of a Shigellosis vaccine in Nha Trang city of
      Viet Nam.
AB  - The acceptability and accessibility of a hypothetical Shigella vaccination
      campaign was explored. A household survey was conducted with 539 randomly
      selected residents of six communes in Nha Trang city of Viet Nam. Four categories
      of acceptability, such as refusers, low acceptors, acceptors, and high acceptors,
      were established, Refusers were significantly more likely to be elderly women and
      were less likely to know the purpose of vaccinations. Low acceptors tended to be
      male, elderly, and live in urban areas. Low acceptors perceived the disease as
      less serious and themselves as less vulnerable than acceptors and high acceptors.
      In terms of accessing vaccination, the commune health centre workers and commune
      leaders were the preferred sources of information and commune health centres the
      preferred location for vaccination. Direct verbal information from healthcare
      providers and audio-visual media were preferred to written information. The
      respondents expressed a desire for knowledge about the side-effects and efficacy
      of the vaccine. These findings are significant for targeting specific messages
      about shigellosis and vaccination to different populations and maximizing
      informed participation in public-health campaigns.

PMID- 15473519
TI  - Cultural and social context of dysentery: implications for the introduction of a
      new vaccine.
AB  - Dysentery, a severe form of diarrhoeal disease, is a major cause of morbidity and
      mortality. Paradoxically, virtually no studies have been conducted to examine
      beliefs and behaviours associated with dysentery. The explanatory model of
      dysentery was explored in a community in Dhaka, Bangladesh, to understand the
      acceptability of a vaccine against dysentery. A local term for bloody dysentery
      is widely known, and residents describe a progression of symptoms, which closely
      mirrors the biomedical model of the disease. Due to the symbolic significance of
      blood loss and the fact that there is much uncertainty regarding treatment,
      bloody dysentery is perceived to be extremely serious. Causal interpretations
      most commonly relate to humoral theories, and remedies involve the consumption of
      'cooling' foods that will reduce the heat associated with dysentery. Despite many
      misconceptions about vaccines and the fact that this approach contradicts
      aetiological explanations, the perceived severity of the illness makes vaccines
      attractive compared to other preventative measures. The results illuminate
      relevant information for the implementation of a new vaccine.

PMID- 15473520
TI  - The health belief model and factors relating to potential use of a vaccine for
      shigellosis in Kaeng Koi district, Saraburi province, Thailand.
AB  - Shigellosis is an important cause of morbidity and mortality throughout the
      world. Approximately, 1.1 million deaths occur a year due to this disease, making
      it the fourth leading cause of mortality worldwide. This paper explores local
      interest in and potential use of a vaccine for shigellosis in Thailand where
      Shigella poses an important public-health concern. Data for this study were
      collected during June-November 2002 from 522 subjects surveyed using a
      sociobehavioural questionnaire in Kaeng Koi district in central Thailand. The
      community demand and likely use of a vaccine were examined in relation to the
      Health Belief Model, which provides analytical constructs for investigating the
      multiple issues of local readiness to accept and access a new vaccine. As the key
      outcome variable, most respondents showed interest in receiving a vaccine against
      dysentery which they thought would provide useful protection against the disease.
      However, there was only a moderate number who perceived dysentery as serious and
      themselves as susceptible to it, although it was perceived to cause some burden
      to and additional expense for families. Most people identified a number of groups
      who were thought to be especially vulnerable to dysentery, such as the elderly,
      pre-school, and school-age children, and poor labourers. Other outcomes of the
      study included the identification of acceptable and convenient sites for its
      delivery, such as government health clinics and private clinics, and respected
      sources for information about the vaccine, such as health clinic personnel and
      community health volunteers. This information suggests that components of the
      Health Belief Model may be useful in identifying community acceptance of a
      vaccine and the means of introducing it. This health information is important for
      planning and implementing vaccine programmes.

PMID- 15473521
TI  - Community-based cluster surveys on treatment preferences for diarrhoea, severe
      diarrhoea, and dysentery in children aged less than five years in two districts
      of Ghana.
AB  - Hospital-based surveillance for severe diarrhoea has been recommended to assess
      the burden of disease due to rotavirus. However, information on healthcare
      seeking patterns of residents in the hospital catchment area is needed first to
      obtain the burden of disease in the community using the hospital data. A
      community-based cluster survey was conducted in two districts of Ghana, each
      served by a single district hospital, to determine the prevalence of severe
      diarrhoea among and treatment preferences for children aged less than five years.
      Caretakers of 619 children in Tema, an urban district, and caretakers of 611
      children in Akwapim South, a rural district, were interviewed. During the month
      preceding the survey, the prevalence of severe diarrhoea in children aged less
      than five years was similar in the two districts (13.6% urban and 12.9% rural),
      as was the proportion of mothers who sought care outside the home (69.0% urban
      and 70.9% rural). 48.8% of urban mothers of children with severe diarrhoea
      visited public/private clinics, 9.5% pharmacies, and 3.6% the district hospital.
      Whereas, 22.8% of rural mothers visited public/private clinics, 19.0% pharmacies,
      and 13.9% the district hospital. Results of the study suggest that rotavirus
      surveillance should be guided by community studies on healthcare-use patterns.
      Where hospital use is low for severe diarrhoea, rotavirus surveillance should
      include other health facilities.

PMID- 15473522
TI  - On food and nutrition policy activities in the USA, Australia, and Norway.
AB  - Formulation and implementation of a national food and nutrition policy is
      important for ensuring good health and quality of life. This study examined the
      formulation and implementation of food and nutrition policies in the USA,
      Australia, and Norway. Library searches, MEDLINE and POPLINE searches, and
      personal communications were used for collecting information and data on
      nutrition activities and policy formulation and implementation in each country.
      These countries were selected because policy activities have been ongoing since
      the 1930s with a clear improvement in the nutritional status of the people.
      Multisectoral participation, conflicts of interest, strategies to alter diet, and
      attempts to deal with new problems have been highlighted and compared. Findings
      of the study may be useful to policy-makers in less-developed countries during
      future policy-making processes.

PMID- 15473523
TI  - A randomized placebo-controlled trial of iron supplementation in breastfed young
      infants initiated on complementary feeding: effect on haematological status.
AB  - To combat iron deficiency manifesting around six months of age, iron-fortified
      complementary feeding has been recommended. In developing countries, in view of
      the poor bioavailability of iron from predominantly cereal-based diets and the
      high cost of fortification, medicinal iron supplementation is an alternative
      intervention. This double-blind randomized placebo-controlled trial was conducted
      from April 1999 to March 2000 in the Out-patient Department of a tertiary
      hospital in New Delhi, India, to evaluate the haematological effects of medicinal
      iron supplementation to breastfed young infants initiated on complementary
      feeding. One hundred healthy non-low birth-weight, predominantly breastfed
      infants aged 4-6 months were randomized into two groups to receive either iron (2
      mg/kg/day) (IS group; n=49) or placebo drops (P group; n=51) beginning with the
      initiation of home-based non-fortified complementary feeding. Haematological
      parameters and anthropometry of mothers and infants were measured at baseline and
      repeated for infants after four and eight weeks of recruitment. Seventy-one
      subjects (35 in the IS group and the 36 in P group) came for the first follow-up,
      and of these, 43 (19 in the IS group and 24 in the P group) reported for the
      second visit. The adjusted (for maternal and baseline infant ferritin) serum
      ferritin levels were significantly higher in the IS group at both the follow-ups
      (p=0.006). The adjusted (for maternal ferritin and baseline infant ferritin)
      change in haemoglobin was significantly higher only at the second follow-up (0.7
      g/dL; 95% confidence interval [CI] 0.3-1.0 g/dL). The adjusted rise in
      haemoglobin was higher in initially anaemic infants (at second follow-up by 1
      g/dL; 95% CI 0.5-1.6 g/dL). Medicinal iron supplementation, at the time of
      initiating complementary feeding, to breastfed young infants resulted in an
      elevation of serum ferritin and haemoglobin. The response was higher in initially
      anaemic infants. From a programmatic perspective, evidence needs to be generated
      on the relative merits of selective (anaemic) versus general supplementation and
      daily versus weekly supplementation.

PMID- 15473524
TI  - Baseline assessment for addressing acute malnutrition by public-health staff in
      Cambodia.
AB  - The objective of this study was to formulate appropriate responses by the public
      health sector to reduce acute malnutrition among children in Cambodia. A cross
      sectional survey to identify wasting together with a simple wealth-ranking
      exercise was conducted. Thereafter, separate focus-group discussions were also
      conducted with mothers of malnourished and non-malnourished children, who
      belonged to the poorest strata, to identify coping mechanisms and to assess
      feeding and hygiene practices. There was no statistical correlation between
      wasting and socioseconomic status (df=3, p=0.06). Reported feeding practices were
      poor, including not giving of colostrum, too early introduction of weaning, low
      feeding frequency, and late introduction of nutritious foods. Healthcare-seeking
      behaviour appeared inadequate, and hand-washing with soap was not practised.
      Acute malnutrition was mainly related to these factors rather than to food
      insecurity. An education campaign in tandem with peer-counselling would be the
      most appropriate option.

PMID- 15473525
TI  - Erythrocyte sedimentation rate may be an indicator for screening of tuberculosis
      patients for underlying HIV infection, particularly in resource-poor settings: an
      experience from India.

PMID- 15473526
TI  - The structure of variation and its influence on the estimation of status:
      indicators of condition of lakes in the Northeast, U.S.A.
AB  - One goal of regional-scale sample surveys is to estimate the status of a resource
      of interest from a statistically drawn representative sample of that resource. An
      expression of status is the frequency distribution of indicator scores capturing
      variability of attributes of interest. However, extraneous variability interferes
      with the status description by introducing bias into the frequency distributions.
      To examine this issue, we used data from a regional survey of lakes in the
      Northeast U.S. collected by the U.S. Environmental Protection Agency's
      Environmental Monitoring and Assessment Program (EMAP). We employ a components of
      variance model to identify sources of extraneous variance pertinent to status
      descriptions of physical, chemical, and biological attributes of the population
      of lakes in the NE. We summarize the relative magnitude of four components of
      variance (lake-to-lake, year, interaction, and residual) for each indicator and
      illustrate how extraneous variance biases the status descriptions. We describe a
      procedure that removes this bias from the status descriptions to produce unbiased
      estimates and introduce a novel method for estimating the 'cost' of removing the
      bias (expressed as either increased sampling uncertainty or additional samples
      needed to achieve the target precision in the absence of bias). We compare the
      relative magnitude of the four variance components across the array of
      indicators, finding in general that conservative chemical indicators are least
      affected by extraneous variance, followed by some nonconservative indicators,
      with nutrient indicators most affected by extraneous variance. Intermediate were
      trophic condition indicators (including sediment diatoms), fish species richness
      and individuals indicators, and zooplankton taxa richness and individuals
      indicators. We found no clear patterns in the relative magnitude of variance
      components as a function of several methods of aggregating fish and zooplankton
      indicators (e.g., level of taxonomy, or species richness vs. numbers of
      individuals).

PMID- 15473527
TI  - Modelling the size separated particulate matter (SSPM10) from vehicular exhaust
      at traffic intersections in Mumbai.
AB  - The study was carried out to predict the size separated particulate matter below
      10 microm size (SSPM10) from vehicular exhausts at traffic intersections using
      modified general finite line source model (GFLSM). Two air quality control
      regions (AQCRs) were selected in Mumbai City for this study. One was industrial
      area (AQCR1) containing the busy intersection, i.e. Marol link road, with the
      heavy inflow of two-three wheelers. And, the other was commercial busy district
      area (AQCR2) containing the busy intersection, i.e. Dadar circle, with a heavy
      traffic flow especially cars. The model was applied at both the traffic
      intersections. The data were collected for modelling study for three winter
      months in 1995 using cascade impactor of nine size ranges. The prediction results
      revealed that modified GFLSM underpredicted the SSPM10 concentrations for all the
      size ranges. However, showed considerable correlation between observed and
      predicted values for the size range below 4.7 microm at both the intersections.
      The relative high concentrations observed in the coarser range of 10-4.7 microm
      are attributed to the resuspension of the roadside particulate matter. Hence, the
      amount of underprediction was more for this range, which was due to the
      characteristics of model that does not take into account the factor for
      resuspension of roadside particulate matter caused by traffic movements. The
      model was also applied to predict the total particulate matter for downwind
      distances from the road intersection. The statistical evaluation of model was
      done, which indicated that the model's performance was good for the finer range
      of particles (below 4.7 microm) with r-square values of 0.49 and 0.57 found at
      both the intersections in AQCR1 and AQCR2, respectively. However, it is not
      unusual that the model uncertainty is likely to exist due to data input errors
      and stochastic fluctuations irrespective of the models accurateness. The
      statistical distribution model was therefore identified using Kolmogorov-Smirnov
      test. At both the intersections, SSPM10 concentration data were found lognormally
      distributed.

PMID- 15473529
TI  - Trace element analyses in an epiphytic lichen and its bark substrate to assess
      suitability for air biomonitoring.
AB  - Total concentrations of Cd, Cr, Fe, Ni, Pb and Zn were compared from October 1996
      to April 1998 in Physcia biziana (Massal.) Zhalbr. v. leptophylla Vezda and in
      the bark of Quercus ilex L. sampled from the same trees at an urban park. Trace
      metal concentrations were also measured in the bark covered by the lichen thalli.
      The lichens showed significantly higher Cr, Fe, Ni and Zn concentrations than
      both uncovered and covered barks. By contrast, both types of barks had higher
      concentrations of Cd and Pb than lichens. Trace elements showed a wide temporal
      variation of concentrations both in the lichens and barks. No relationship was
      found between the analysed matrices as regards the time course of trace element
      concentrations.

PMID- 15473530
TI  - Assessment of hydraulic restoration of San Pablo Marsh, California.
AB  - Inter-tidal marshes are dynamic diverse ecosystems at the transition zone between
      terrestrial and ocean environments. Geomorphologically, inter-tidal salt marshes
      are vegetated land-forms at elevations slightly greater than mean tidal levels
      that have distributed channels formed under ebb (drainage) tidal flows that widen
      and deepen in the seaward direction. The drainage channels enable tidal flows to
      circulate sediments and nutrients through the marsh system during normal tidal
      events, while depositing sediments during storm or seismic events. This dynamic
      system encourages considerable biodiversity while simultaneously providing water
      quality enhancement features that service marsh terrestrial life and marine life
      in the estuary. Reservoir creation limiting sediment transport, anticipated large
      increases in sea levels as well as agricultural and urban development have
      resulted in significant loss of inter-tidal marshes and subsequent adverse
      impacts on waterfowl, infauna and fisheries. The complex and continuously
      changing marsh channel hydraulics and sedimentary processes have severely
      constrained quantitative modeling of these marsh systems such that
      restoration/creation efforts remain something of an empirical science and further
      assessments are needed. The purpose of this paper is to outline current
      understanding of salt marsh hydrodynamics, sediment accretion processes and
      subsequent response of marsh vegetation to set the stage for assessment of a
      marsh restoration effort along San Pablo Bay near San Francisco, California.
      Several kilometers of drainage channels were constructed in a 624 ha disturbed
      salt marsh to restore tidal circulation and vegetation so as to enhance habitat
      for threatened species (e.g. clapper rail, harvest mouse, delta smelt and
      potentially anadromous fish species). Two distinct drainage channel systems
      ('east' and 'west') were installed having similar channel dimensions common to
      salt marshes in the region, but having design bankfull tidal prism volumes
      differing by a factor of two. Following channel excavation, main channel tidal
      flows and sediment loads as well as marsh sediment accretion rates were monitored
      to assess the relative success of the excavation in restoring tidal circulation
      and vegetation (Salicornia spp.) to the marsh. Annual aerial surveys corroborated
      with ground-truthing indicated that marsh vegetation rapidly expanded, from 40 to
      85% coverage several years following excavation. The 'east' channel intake was
      nearly completely silted in within three years. However, channel surveys and flow
      measurements indicated that the 'east' channel system tidal prism was only about
      1200 m3, more than an order of magnitude less than that of the stable 'west'
      channel system. Marsh sediment accretion rates were on the order of 7-8 mm yr(
      1), a rate common to the Pacific coast region that exceeds estimated sea level
      rise rates of approximately 2 mm yr(-1). East channel network siltation resulted
      in storm and spring tidal flood ponding such that marsh vegetation coverage
      decreased to 51% of the marsh area and related habitat expansion decreased. These
      results are considered in terms of the primary inter-tidal marsh factors
      affecting possible restoration/creation strategies.

PMID- 15473528
TI  - Heavy metals monitoring using bivalves from Mediterranean Sea and Red Sea.
AB  - The concentrations of heavy metals (Cd, Co, Cu, Fe, Mn, Ni, Pd and Zn) were
      measured in the Bivalves (Modiolus auriculatus and Donax trunculus) collected
      from the Egyptian coasts of Mediterranean Sea and Brachiodonates sp. from the
      Egyptian coasts of Red Sea. The average concentrations of the heavy metals
      analyzed exhibited the following decreasing order: Fe > Zn > Cu > Mn > Ni > Co >
      Pb > Cd for both Mediterranean Sea and Red Sea. The analyses of Cd, Co, Ni, Pb,
      and Zn showed higher average concentrations for samples collected from Red Sea
      than that collected from Mediterranean Sea, while Fe, Cu and Mn showed the
      reverse results. Fe was used as a normalizing agent for all studied metals and
      exhibited presence of two locations from each of Mediterranean Sea and Red Sea
      have anthropogenic inputs of heavy metals. These results suggest that the coastal
      area in both Mediterranean Sea and Red Sea of Egypt might be considered
      relatively unpolluted with heavy metal.

PMID- 15473531
TI  - Ammonia monitoring in Switzerland with passive samplers: patterns, determinants
      and comparison with modelled concentrations.
AB  - Gaseous ammonia (NH3) is an important form of N deposition to ecosystems, but it
      is not being routinely monitored in Switzerland. Therefore, a study was conducted
      to estimate annual means and seasonal patterns of NH3 concentrations for
      different site types in Switzerland, and to compare annual measured and modelled
      NH3 concentrations. NH3 concentrations were measured using the 'Zurcher' passive
      sampler, a Palmes type sampler with an acidic solution as absorbent. Twenty-four
      sampling sites were run for one year, and 17 for two years. The samplers were
      changed fortnightly or monthly. Spatial emission patterns were mapped by
      combining information on (1) the location of emission sources, (2) national
      statistics on NH3-emitting activities and (3) activity-specific emission factors.
      The spatial resolution was one hectare. The mean annual NH3 concentration in the
      ambient air of the 41 sites was 2.5+/-0.3 microg m(-3) (mean+/-standard error).
      It ranged from 0.4 to 7.5 microg m(-3). The site type and the season were the
      most important factors explaining the variation in the seasonal mean
      concentration. NH3 concentrations were highest in intensively used agricultural
      areas and in cities, and lowest in Alpine sites remote from emission sources. At
      39 out of 41 sites, the NH3 concentrations were higher in summer (3.1+/-0.3
      microg m(-3)) than in winter (2.0+/-0.3 microg m(-3)). Modelled NH3
      concentrations did not systematically deviate from measured concentrations (r2 =
      0.69). With the combined monitoring and modelling approach, it is now possible to
      obtain a reasonable and consolidated picture of the overall NH3 situation in
      Switzerland.

PMID- 15473532
TI  - Development of a standardised approach to river habitat assessment in Australia.
AB  - Despite the demonstrated utility of the Australian River Assessment Scheme
      (AUSRIVAS) to provide national-scale information on the biological condition of
      rivers, there is no commensurate scheme that can provide standardised information
      on physical habitat. Existing habitat assessment methods are not suitable for
      implementation on a national scale, so we present a new habitat assessment
      protocol that incorporates favorable elements of existing methods. Habitat
      Predictive Modelling forms the basis for the protocol because it can predict the
      occurrence of local-scale features from large-scale data, uses the reference
      condition concept, can be modified to incorporate a range of biologically and
      geomorphologically relevant variables, and employs a rapid survey approach.
      However, the protocol has been augmented with geomorphological variables and
      incorporates principles of hierarchy and geomorphological river zonation. There
      are four sequential components to the implementation of the protocol: reference
      site selection, data collection, predictive model construction and assessment of
      test sites using the predictive models. Once implemented, the habitat assessment
      protocol will provide a standardised tool for the assessment of river habitat
      condition at a variety of governance levels.

PMID- 15473533
TI  - Spatial analysis and indicator building for metal accumulation in mosses.
AB  - Mosses are used as passive accumulation monitors for metal accumulation in
      terrestrial ecosystems. Under leadership of the Federal Agency for Environmental
      Protection Germany took part in the previous European-wide moss monitoring
      campaigns 1990, 1995 and 2000. The investigations accomplished thereby cannot be
      presented completely in this article. The remarks rather concentrate on
      methodical aspects of the statistical data analysis. In Chapter 2 the design of
      data collection is summarized. Chapter 3 treats the geostatistical analysis and
      transformation of point data to areal information. Chapter 4 describes the
      aggregation of the element-specific metal concentrations in mosses to a spatially
      and temporally differentiated indicator of metal accumulation by means of
      descriptive and multivariate statistics. The work presented is only a small part
      of geostatistics and multivariate statistics which fit for analysis of moss
      monitoring data. Taking the results presented here as a basis, the following
      steps would further be of great importance: cluster-analytic evaluation of the
      results of the Moss Monitoring 1990 and 1995, detailing the cluster results using
      additional empirical and location describing information (e.g. moss species,
      ecoregions, site and species specific variability of metal accumulation) as well
      as optimizing the indicator buildung by testing of multivariate statistical
      regression models (e.g. Classification and Regression Trees).

PMID- 15473535
TI  - Elements of a predictive model for determining beach closures on a real time
      basis: the case of 63rd Street Beach Chicago.
AB  - Data on hydrometeorological conditions and E. coli concentration were
      simultaneously collected on 57 occasions during the summer of 2000 at 63rd Street
      Beach, Chicago, Illinois. The data were used to identify and calibrate a
      statistical regression model aimed at predicting when the bacterial concentration
      of the beach water was above or below the level considered safe for full body
      contact. A wide range of hydrological, meteorological, and water quality
      variables were evaluated as possible predictive variables. These included wind
      speed and direction, incoming solar radiation (insolation), various time frames
      of rainfall, air temperature, lake stage and wave height, and water temperature,
      specific conductance, dissolved oxygen, pH, and turbidity. The best-fit model
      combined real-time measurements of wind direction and speed (onshore component of
      resultant wind vector), rainfall, insolation, lake stage, water temperature and
      turbidity to predict the geometric mean E. coli concentration in the swimming
      zone of the beach. The model, which contained both additive and multiplicative
      (interaction) terms, accounted for 71% of the observed variability in the log E.
      coli concentrations. A comparison between model predictions of when the beach
      should be closed and when the actual bacterial concentrations were above or below
      the 235 cfu 100 ml(-1) threshold value, indicated that the model accurately
      predicted openings versus closures 88% of the time.

PMID- 15473534
TI  - Ozone exposures and implications for vegetation in rural areas of the central
      Appalachian Mountains, U.S.A.
AB  - The United States is making the transition from the 1979 1 hr maximum ozone
      standard to the newly adopted 8 hr ozone standard (3 yr average of the 4th
      highest maximum 8 hr ozone concentration). Consequently, we analyzed and compared
      ozone concentrations under both standards from a variety of monitoring sites
      throughout the central Appalachian region of Kentucky (KY), West Virginia (WV),
      and Virginia (VA). Data from 1988-1999 were used to determine how ozone exposure
      between the two metrics compared for remote sites. Most sites exceeded the 1 hr
      standard in 1988-1990 due to the 3 yr averaging and multiple high ozone
      concentrations that occurred over the region in 1988. All sites were in
      compliance with the 1 hr standard every year after 1991. It was much more common
      for the ozone exposure to exceed the 8 hr standard, particularly from 1997-1999.
      Many sites showed exceedences beginning in 1995; Big Meadows (VA) exceeded the 8
      hr standard all years except 1994 and 1996. Response of vegetation to ozone in
      these areas was determined using the combination of W126 values (sigmoidally
      weighted exposure index), the number of hours that average concentrations > or =
      0.10 ppm (N100), and the presence of moderate or more extreme droughts. In
      general, W126 and N100 values suggested that negative vegetation growth responses
      over most of the 12 yr would have been minimal for most sites, even for those
      exceeding ozone standards. Drought-induced stomatal closures would have
      overridden more extreme negative growth responses at all but the Big Meadows site
      in 1988.

PMID- 15473536
TI  - Detection of lead in vegetables with new chromogenic reagent by
      spectrophotometry.
AB  - A new simple, rapid selective and highly sensitive chromogenic reagent dibromo-p
      methyl-carboxyazo (DBMCA) was synthesized and studied in detail for the
      spectrophotometric detection of lead. In 0.25 M phosphoric acid medium, which
      greatly increases the selectivity, Lead reacts with DBMCA to form a 1:2 blue
      complex having a sensitivity absorption peak at 646 nm. Under optimal conditions,
      Beer's Law is obeyed over the range from 0.09 to 0.8 microg mL(-1) Pb (II) and
      the apparent molar absorptivity is 1.03 x 10(5) mL(-1) cm(-1). The detection
      limit and the variation coefficient were found to be 2.12 microg mL(-1) and 1.0%
      respectively. It is found that, except for Ca (II) and Ba (II) all foreign ions
      studied do not interfere with detection. The interference caused by Ca (II) and
      Ba (II) can be easily eliminated by prior extraction with potassiumiodide
      methylisobutylketone. The proposed method has been applied successfully for to
      the detection of Lead in vegetable leaves with good results.

PMID- 15473537
TI  - Sampling considerations for establishment of baseline loadings from forested
      watersheds for TMDL application.
AB  - Five methods for estimating maximum daily and annual nitrate (NO3) and suspended
      sediment loads using periodic sampling of varying intensities were compared to
      actual loads calculated from intensive stormflow and baseflow sampling from
      small, forested watersheds in north central West Virginia to determine if the
      less intensive sampling methods were accurate and could be utilized in TMDL
      development. There were no significant differences between the annual NO3 load
      estimates using non-intensive sampling methods and the actual NO3 loads. However,
      maximum daily NO3 loads were estimated less accurately than annual loads. The
      ability to estimate baseline NO3 loads fairly accurately with non-intensive
      concentration data is attributed to the small fluctuation in NO3 concentrations
      over flow and time, particularly during storms. By contrast, suspended sediment
      exports determined by any of the non-intensive methods varied significantly and
      widely from and compared poorly to the actual exports for both daily and annual
      methods. Weekly sampling better approximated actual annual exports, but there
      were no significant statistical differences among weekly, monthly, and quarterly
      estimates. Suspended sediment concentrations varied widely within and among storm
      events, so that accurate estimates of total annual or maximum daily loads could
      not be obtained from infrequent sampling.

PMID- 15473538
TI  - A season-dependent variation of genotoxicity of surface water samples from Taihu
      Lake, Yangzte delta.
AB  - The present study is to assess a year round change of genotoxicity of surface
      water in Taihu Lake, Yangtze delta. The water samples were collected in spring,
      summer, autumn and winter of 2001, respectively. The bacterial L-arabinose
      resistance forward mutation test (ara test), along with the Ames test, was
      performed for the evaluation of time profile of mutagenicity of the surface water
      samples. The strong genotoxic potentials were detected in the near-shore area,
      especially in the vicinity to the major city. All the samples collected from the
      lake center and areas distant from dense human activity showed genotoxicity-free
      in year round time. Intensified human activity along the lake may play an
      important role for the genotoxic pollution. By comparison of the samples from
      year round, the winter samples showed the strongest mutagenic potential of all
      seasons, which indicates that meteorological and hydrological factors also affect
      the water quality. The impact of dense human activity, improper management and
      season change should be put into consideration for designing an effective
      remediation project in the lake basin area.

PMID- 15473539
TI  - Characterisation of airborne particulate pollution in the Cu smelter and former
      mining town of Karabash, South Ural Mountains of Russia.
AB  - Airborne total suspended particulates (TSP), dusts from smelter blast furnace and
      converter stacks, and filtrates of snow melt waters have been characterised in
      the Cu smelter and former mining town of Karabash, Russia. TSP was collected at
      sites up- and downwind of the smelter and large waste and tailings dumps (Oct.
      2000 and July 2001). Methods for particle size, mineralogical and elemental
      determinations have been tested and described, and a new PSD-MicroSOURCE XRD
      technique developed for the mineralogical analysis of microsamples on filter
      substrates. TSP in downwind samples has a mean equivalent spherical diameter of
      0.5 microm (s.d. = 0.2) and was found to be 100% respirable. The main element of
      human health/environmental concern, above Russian maximum permitted levels (1
      microg m(-3), average over any time period), was Pb which was measured at 16-30
      microg m(-3) in downwind samples. Individual particulates mainly consisted of
      complex mixtures of anglesite (PbSO4), Zn2SnO4 and poorly ordered Zn sulphates.
      From experimental and theoretical considerations, a high proportion of contained
      Pb, Zn, Cd and As in this material is considered to be in a readily bioavailable
      form. Chemical and mineralogical differences between the TSP, stack dusts and
      snow samples are discussed, as well as the implications for human and regional
      environmental health.

PMID- 15473540
TI  - A zone-wise ecological-economic analysis of Indian wetlands.
AB  - In view of their sensitivity and importance, an ecological-economic analysis of
      wetlands has been carried out for various Indian states. Subsequently, the
      ecological wealths of different zones (north, south, east and west) have been
      computed and compared. Amongst states, Karnataka (7896.5 million US dollars yr(
      1)), Gujarat (7689.4 million US dollars yr(-1)) and Andhra Pradesh (7670.9
      million US dollars yr(-1)) are found to be the richest, whereas Nagaland (3.1
      million US dollars yr(-1)), Meghalaya (5.9 million US dollars yr(-1)) and Sikkim
      (15.9 million US dollars yr(-1)) turn out to be the poorest. Amongst different
      zones, Southern Zone turns out to be the richest and the Northern Zone poorest. A
      ratio called ANR [Artificial (A) Wetland Wealth to Natural (N) Wetland Wealth
      Ratio (R)] has also been devised, which is the ratio of the ecological-economic
      values of artificial and natural wetlands. In other words, this ratio indicates
      the level of environmental concern of a given region. ANR ratio is found to be
      the highest for Madhya Pradesh (564.1) and Karnataka (159.8) states.

PMID- 15473542
TI  - Using slides to test for changes in crown defoliation assessment methods. Part I:
      Visual assessment of slides.
AB  - In this study we used photographs of tree crowns to test whether the assessment
      methods for tree defoliation in Switzerland have changed over time. We randomly
      selected 24 series of slides of Norway spruce with field assessments made between
      1986 and 1995. The slides were randomly arranged and assessed by three experts
      without prior knowledge of the year when the slide was taken or the tree number.
      Defoliation was assessed using the Swiss reference photo guide. Although the
      correlations between the field assessments and slide assessments were high
      (Spearman's rank correlation coefficient ranged between 0.79 and 0.83), we found
      significant differences between field and slide assessments (4.3 to 9%
      underprediction by the slide assessors) and between the slide assessments.
      However, no significant trends in field assessment methods could be detected.
      When the mean differences between field and slide assessments were subtracted, in
      some years, field assessors consistently underpredicted (1990, 1992) or
      overpredicted defoliation (1987, 1991). Defoliation tended to be overpredicted in
      slides taken against the light, and underpredicted for trees with more than 25%
      crown overlap. We conclude that slide series can be used to detect changes in
      assessment methods. However, potential observer bias calls for more objective
      methods of assessment.

PMID- 15473541
TI  - Minimax statistical models for air pollution time series. Application to ozone
      time series data measured in Bordeaux.
AB  - This paper deals with the application of l(infinity) (or minimax) optimization
      techniques to statistical modelling of high frequency air pollution data. The
      method was applied to ground-level ozone time-series data measured in Bordeaux
      over 4 years from 1998 to 2001. The aim of model building was to develop
      predictive models in order to provide forecasts of the maximal daily ground-level
      ozone concentration. Experimental results from this case study indicate that such
      techniques could be more appropriate than the commonly used l2 setting if only
      good estimation of high levels is of interest. When the free parameters are
      fitted by means of l(infinity) optimization techniques, the forecasting errors
      are more evenly distributed amongst the data points, resulting in a better
      estimation of high values. The paper compares the quality of forecasts produced
      by both a linear and a nonlinear model, using l2 and l(infinity) parameter
      optimization.

PMID- 15473543
TI  - Recent trends and patterns of nutrient concentrations in small agricultural
      streams in Sweden.
AB  - Long-term median total phosphorus (TotP) and total nitrogen (TotN) concentrations
      were 0.08 and 5.5 P/N (mg L(-1)), respectively, in 10 agricultural streams
      monitored since 1988 in Sweden. The areas of the respective catchments are 2-20
      km2. The period 1992/2002 was characterised by stable hydrological conditions
      without any flow trends in nearly all of the streams. The highest average TotP
      concentration, 0.17 mg P L(-1), was found in a small agricultural stream in the
      largest Swedish agricultural plain. The soil texture is here characterised by a
      large specific surface area of the soil particles, and the agriculture by cereal
      production. The second highest average TotP concentration, 0.14 mg P L(-1), was
      measured in the surface water from a catchment characterised partly by clay soils
      and by production of potato, spring cereals and grass. This catchment had twice
      as many fields with a calculated high risk for P losses compared with another
      monitored catchment in the same watershed (River Ronnea). There was a significant
      downward TotP trend during 1992/2002 of 0.0012 mg P L(-1) yr(-1) (Sen's slope
      estimator) in the catchment where many fields risk P losses and which had a
      reduced P manure application rate of -20% during 1995/2000. In recent years
      practically no manure has been spread during autumn. Bypass flow of nitrate
      through one soil has been suggested to influence the LOWESS (LOcally WEighted
      Scatterplot Smoothing) fitting curve of TotN. Total nitrogen concentration
      decreased in most of the catchment. The average downward slope was similar to a
      general TotN reduction of 0.069 mg N L(-1) yr(-1). During the period 1992/2002
      this was equal to slightly more than 10 per cent. Cultivation of catch crops was
      relatively uncommon until 2002, but this practice is expected to expand to larger
      areas during 2003 and in the future.

PMID- 15473544
TI  - Assessing the relative severity of stressors at a watershed scale.
AB  - Water quality monitoring data are usually used independently to report on the
      condition of streams and watersheds. For example, watersheds are often rated as
      good, fair, or poor with regard to a single stressor or with regard to an index
      of biotic integrity. The utility of monitoring data may be enhanced by
      integrating stressor-response information with the observed stressor data, and
      reporting stressor levels in terms of their relative effects upon valued
      ecological resources. We estimated stressor-response relationships at the
      regional scale using data collected in the Eastern Cornbelt Plains Ecoregion of
      Ohio. Generalized additive models were used to visualize stressor-response
      relationships. Piecewise linear functions and simple linear functions were then
      used to parameterize the observed responses. Parameters derived from the regional
      models were used to scale observations of stressors in the Big Darby Creek
      watershed, OH. After scaling, stressors were compared in terms of their spatial
      distribution and in terms of the severity with which they influenced the
      biological endpoint of interest. Stressors most strongly associated with the
      current ecological condition of the watershed were identified. In the Big Darby
      Creek watershed, decreases in substrate quality were associated with the most
      severe decrements in biological condition. At smaller decrements in biological
      condition, three stressors were important: substrate quality, riparian quality,
      and increased concentrations of NOx.

PMID- 15473545
TI  - Decomposed gosling feet provide evidence of insecticide exposure.
AB  - Canada goose goslings were exposed to turf sprayed with DZN diazinon 50W
      application (2.24 kg a.i./ha). The control plot was subjected to a water
      application. One foot from each bird was placed outdoors for 7 d to decompose and
      the other foot was kept frozen. Diazinon residues were analyzed on both feet.
      Results showed that diazinon was detected from undecomposed and decomposed feet
      of the birds. Diazinon residues were below the level of detection (<0.01 ppm,
      a.i.) on the feet from the control goslings. Decomposed feet may be used for
      determining insecticide exposure when the traditional matrices are not available.

PMID- 15473546
TI  - Critical loads of acidity for forest soils and relationship to forest decline in
      the northern Czech Republic.
AB  - Critical load calculations in the Czech part of 'the Black Triangle' show
      exceedance of critical load in 75% of the forest area. A comparison with forest
      damage data shows an insignificant tendency toward more forest damage in areas
      with high exceedance. We conclude that high exceedance of critical load is a
      probable contributing factor to forest damage in the area.

PMID- 15473547
TI  - Organochlorine pesticide residues in wheat and drinking water samples from
      Jaipur, Rajasthan, India.
AB  - The organochlorine pesticide contamination in dietary sources has caused serious
      threat to the human progeny. The present study was therefore conducted to
      evaluate the pesticide contamination in wheat flour and drinking water from
      Jaipur City, Rajasthan, India using Gas Chromatograph. All the wheat and water
      samples were found to be contaminated with various organochlorine pesticide
      residues of DDT and its metabolites, HCH and its isomers, heptachlor and its
      expoxide and aldrin. The amount of pesticide detected in wheat flour was higher
      than the permissible limits prescribed by WHO/FAO. In drinking water only a few
      pesticides exceeded the permissible limits. Seasonal variations of pesticides
      residues were also observed during the study period.

PMID- 15473548
TI  - Effects of houseboats on organisms of the La Parguera Reserve, Puerto Rico.
AB  - As coastal development increases so too does the number of artificial floating
      and permanent structures. It has been postulated that because of their size, many
      houseboats are similar to permanent structures in that they shade a significant
      portion of the benthos and thereby limit production by benthic flora. On the
      other hand, these structures can benefit biotic communities by providing sites
      for attachment of organisms in a substrate-limited environment and both habitat
      and food sources for fish. In this study, we examined whether houseboats benefit
      or harm the ecological integrity of a typical seagrass dominated system, at La
      Parguera, Puerto Rico. We performed a benthic survey to compare the diversity and
      health of seagrasses under houseboats to that at control locations. Species
      diversity (0-0.79) varied significantly among sites, but this variability was not
      attributed to the houseboats. Rather, the variability appeared related to the
      proximity of the study locations to new development along the shoreline. Average
      seagrass blade density and length were 52.7 blades/m(-2) and 23.6 cm,
      respectively. Neither parameter differed between houseboat and control areas;
      however, both varied significantly among sites. In addition, boat hulls were
      heavily encrusted with invertebrates. The overall averages of species diversity
      and richness of sessile organisms on hulls of the houseboats were 1.13 and 4.83,
      respectively. Fish also utilized these structures. Our results indicate that
      houseboats did not directly harm the seagrass communities at La Parguera
      primarily because of sound environmental management of wastes and mooring
      techniques.

PMID- 15473549
TI  - Synthesis of HNO3 from organic matter and its influence on nutrient replenishment
      in forest soils.
AB  - Chemical analyses during a decade of bulk precipitation, throughfall, humus water
      and soil water in forest plots ranging from sand to silt of Pleistocene origin in
      Flanders (N-Belgium) prove that previous and present weathering is predominantly
      due to synthesis of HNO3 from soil organic matter. The HNO3 reacts with silicates
      and possibly PO4(3-) species, releasing Al, Fe, nutrient base cations and H2PO4-,
      and is transformed into NO3-. In all soils solubilized Al3+ is predominantly
      associated with NO3- and with some organic bases in the coarse-textured soils
      with undisturbed or previously plowed spodic B horizon. The amounts of ions
      leached, especially Al3+ and NO3-, are much higher in the sandy than in the silty
      soils as a result of a stronger neutralization of acidity in the silty soils.
      Nutrients, leached from the soil, have to be replenished in some way for a
      sustained forest growth. N- and S-species must come from the atmosphere. Basic
      cations and P-species have to be supplied out of the solid phase. The
      concentrations of NO3- in the soil water show that the liberation of these
      elements from the solid phase is performed by HNO3. Especially in the coarse
      textured soils the need for NO3- is high. Therefore, instead of being a real
      hazard for the forest ecological system, supplementary addition of HNO3 or NH3
      can be beneficial.

PMID- 15473550
TI  - Evaluating the efficiency of coagulation in the removal of dissolved organic
      carbon from reservoir water using fluorescence and ultraviolet photometry.
AB  - The present study used ultraviolet absorption (UVa) and the florescence intensity
      (FI) to evaluate the coagulation efficiency for removing dissolved organic carbon
      (DOC) in the raw water from Min-Ter, Li-Yu-Ten and Yun-Ho-Shen reservoirs in
      Taiwan. The results indicated that the ratio of DOC removal rate and FI removal
      rate was maintained at about 1 at various coagulant dosages. However, the ratio
      of DOC removal rate and UVa removal rate decreased as the coagulant dosage
      increased. In addition, after coagulation, the use of florescence intensity
      instead of total organic carbon (TOC) is better than UVa for measuring the DOC
      removal rate of the raw waters gathered in different months from the three
      reservoirs. Furthermore, a good linear relationship between florescence intensity
      and DOC removal rate was observed, and the DOC/FI ratio of raw water from each
      reservoir can be used to predict the DOC residual concentration after enhanced
      coagulation. This result shows that fluorescence analysis can be used for on-line
      and continuous monitoring the effectiveness of organic matter removal in water
      treatment.

PMID- 15473551
TI  - Effect of benzene, toluene, ethylbenzene, and p-xylene (BTEX) mixture on
      biodegradation of methyl tert-butyl ether (MTBE) and tert-butyl alcohol (TBA) by
      pure culture UC1.
AB  - The effect of a BTEX mixture on the biodegradation of methyl tert-butyl ether
      (MTBE) and its degradation intermediate, tert-butyl alcohol (TBA) was
      investigated in the pure bacterial culture UC1, which has been identified to be a
      strain of the known MTBE-degrader PM1 based on greater than 99% 16S rDNA
      similarity. Several degradation studies were carried out on UC1 at three initial
      concentration levels of MTBE or TBA: 6-7; 15-17; and 40-45 mg/l, both with and
      without BTEX present cumulatively at about half of the MTBE or TBA molar mass in
      the system. The BTEX mixture was observed not to affect either the rate or the
      degradation lag period of MTBE or TBA degradation, except that the TBA
      degradation rate actually increased when BTEX was present initially in the
      highest concentration studies. When serving as the sole substrate, the MTBE
      degradation rate ranged from 48 +/- 1.2 to 200 +/- 7.0 mg(MTBE)/g(dw) h, and the
      TBA degradation rate from 140 +/- 18 to 530 +/- 70 mg(TBA)/g(dw) h. When present
      with BTEX, MTBE and TBA rates ranged from 46 +/- 2.2 to 210 +/- 14 and 170 +/- 28
      to 780 +/- 43 mg(TBA)/g(dw) h, respectively. In studies where varying
      concentrations of TBA were present with 5 mg/l MTBE, both compounds were degraded
      simultaneously with no obvious preference for either substrate. In the highest
      concentration study of TBA with 5 mg/l MTBE, BTEX was also observed to increase
      the ultimate rate of TBA degradation. In addition to exploring the affect of
      BTEX, this study also provides general insight into the metabolism of MTBE and
      TBA by pure culture UC1.

PMID- 15473552
TI  - A stereoselective carbon-nitrogen lyase from Ralstonia sp. SLRS7 cleaves two of
      three isomers of iminodisuccinate.
AB  - Following biodegradation tests according to the OECD guidelines for testing of
      chemicals 301F different degradation rates were observed for the three
      stereoisomers of iminodisuccinate (IDS). A strain was isolated from activated
      sludge, which used two of three isomers, R,S-IDS and S,S-IDS, as sole source of
      carbon, nitrogen, and energy. The isolated strain was identified by 16S-rDNA and
      referred to as Ralstonia sp. SLRS7. An IDS-degrading lyase was isolated from the
      cell-free extract. The enzyme was purified by three chromatographic steps, which
      included anion-exchange chromatography, hydrophobic interaction chromatography
      and gel filtration. The lyase catalysed the non-hydrolytic cleavage of IDS
      without requirement of any cofactors. Cleavage of S,S-IDS led to the formation of
      fumaric acid and L-aspartic acid. Interestingly R,S-IDS yielded only D-aspartic
      acid besides fumaric acid. R,R-IDS was not transformed. Thus, the IDS-degrading
      enzyme is a carbon-nitrogen lyase attacking only the asymmetric carbon atom
      exhibiting the S-configuration. Besides S,S-IDS and R,S-IDS cleavage, the lyase
      catalysed also the transformation of certain S,S-IDS metal complexes, namely
      Ca(2+)-, Mg(2+)- and Mn(2+)-IDS. The maximum enzyme activity was found at pH 8.0
      8.5 and 35 degrees C. SDS-PAGE analysis revealed a single 57-kDa protein band.
      The native enzyme was estimated to be around 240 kDa indicating a homotetramer
      enzyme.

PMID- 15473553
TI  - Biological reduction of TNT as part of a combined biological-chemical procedure
      for mineralization.
AB  - The explosive 2,4,6-trinitrotoluene (TNT), one of the most abundant and
      persistent contaminants at former armament factories and military sites, was
      cometabolically reduced by sludge (mixed culture) from a sewage plant in order to
      facilitate mineralization in a subsequent photochemical treatment. Under aerobic
      conditions, the main reduction products were aminodinitrotoluenes (ADNTs). A
      greater amount of the nitroaromatics (ca. 30%) was adsorbed by the sludge as was
      shown by a complete balance of the process using 14C-TNT. Under anaerobic
      conditions, TNT was further converted into ADNTs and diaminonitrotoluenes (DANTs)
      while only negligible adsorption to the sludge occured.

PMID- 15473554
TI  - Enhanced biodegradation of Casablanca crude oil by a microbial consortium in
      presence of a rhamnolipid produced by Pseudomonas aeruginosa AT10.
AB  - The biodegradation of oil products in the environment is often limited by their
      low water solubility and dissolution rate. Rhamnolipids produced by Pseudomonas
      aeruginosa AT10 were investigated for their potential to enhance bioavailability
      and hence the biodegradation of crude oil by a microbial consortium in liquid
      medium. The characterization of the rhamnolipids produced by strain AT10 showed
      the effectiveness of emulsification of complex mixtures. The addition of
      rhamnolipids accelerates the biodegradation of total petroleum hydrocarbons from
      32% to 61% at 10 days of incubation. Nevertheless, the enhancement of
      biosurfactant addition was more noticeable in the case of the group of
      isoprenoids from the aliphatic fraction and the alkylated polycyclic aromatic
      hydrocarbons (PHAS) from the aromatic fraction. The biodegradation of some
      targeted isoprenoids increased from 16% to 70% and for some alkylated PAHs from
      9% to 44%.

PMID- 15473555
TI  - Does bioavailability limit biodegradation? A comparison of hydrocarbon
      biodegradation and desorption rates in aged soils.
AB  - In order to determine whether bioavailability limits the biodegradability of
      petroleum hydrocarbons in aged soils, both the biodegradation and abiotic
      desorption rates of PAHs and n-alkanes were measured at various time points in
      six different aged soils undergoing slurry bioremediation treatment. Alkane
      biodegradation rates were always much greater than the respective desorption
      rates, indicating that these saturated hydrocarbons apparently do not need to be
      dissolved into the aqueous phase prior to metabolism by soil microorganisms. The
      biodegradation of PAHs was generally not mass-transfer rate limited during the
      initial phase, while it often became so at the end of the treatment period when
      biodegradation rates equaled abiotic desorption rates. However, in all cases
      where PAH biodegradation was not observed or PAH removal temporarily stalled,
      bioavailability limitations were not deemed responsible for this recalcitrance
      since these PAHs desorbed rapidly from the soil into the aqueous phase.
      Consequently, aged PAHs that are often thought to be recalcitrant due to
      bioavailability limitations may not be so and therefore may pose a greater risk
      to environmental receptors than previously thought.

PMID- 15473556
TI  - Bioremediation of textile azo dyes by aerobic bacterial consortium.
AB  - An aerobic bacterial consortium consisting of two isolated strains (BF1, BF2) and
      a strain of Pseudomonas putida (MTCC1194) was developed for the aerobic
      degradation of a mixture of textile azodyes and individual azodyes at alkaline pH
      (9-10.5) and salinity (0.9-3.68 g/l) at ambient temperature (28 +/- 2 degrees C).
      The degradation efficiency of the strains in different media (mineral media and
      in the Simulated textile effluent (STE)) and at different dye concentrations were
      studied. The presence of a H2O2 independent oxidase-laccase (26.5 IU/ml) was
      found in the culture filtrate of the organism BF2. The analysis of the degraded
      products by TLC and HPLC, after the microbial treatment of the dyes showed the
      absence of amines and the presence of low molecular weight oxidative degradation
      products. The enzymes present in the crude supernatant was found to be reusable
      for the dye degradation.

PMID- 15473557
TI  - A worrisome practice.

PMID- 15473559
TI  - Are clinical ladders the way to keep RNs at the bedside?

PMID- 15473558
TI  - Unlicensed personnel doing nursing duties prompts RN to walk.

PMID- 15473560
TI  - A lack of sterile technique is not a joking matter.

PMID- 15473561
TI  - Hands-on help: assessing heart sounds.

PMID- 15473562
TI  - Pediatric psych cases and how you can help.

PMID- 15473563
TI  - How to help wounds heal.

PMID- 15473564
TI  - The enigma of the Gypsy patient.

PMID- 15473565
TI  - Intimate partner violence.

PMID- 15473566
TI  - My escape from abuse.

PMID- 15473567
TI  - Rediscovering my passion.

PMID- 15473569
TI  - Taking on the night shift.

PMID- 15473568
TI  - Get ready for the virtual ICU.

PMID- 15473570
TI  - We need a bill of rights with teeth.

PMID- 15473572
TI  - Have license, will travel: is interstate licensure in your future?

PMID- 15473573
TI  - Health professionals travel to far away places to make a difference.

PMID- 15473574
TI  - Nurses choosing entrepreneurship path.

PMID- 15473575
TI  - Orcein, a traditional stain revealed: some introductory remarks.

PMID- 15473576
TI  - Orcein and litmus.
AB  - Orcein was separated into 14 dyes by partition chromatography. Their
      constitutions were determined mainly by spectroscopy and led to formulae that are
      derived from 7-amino-2-phenoxazone, 7-hydroxy-2-phenoxazone, and 7-amino-2
      phenoxazime, and that were confirmed by syntheses. The major constituent of
      litmus is assembled polymerically from 7-hydroxy-2-phenoxazone chromophores. The
      mechanism of formation is elucidated.

PMID- 15473577
TI  - Current applications of orcein in histochemistry. A brief review with some new
      observations concerning influence of dye batch variation and aging of dye
      solutions on staining.
AB  - Current uses of orcein to demonstrate elastic fibers and, following permanganate
      oxidation (Shikata's modification), hepatitis B surface antigen, copper
      associated protein, and sulfated mucins, are reviewed. Variations in staining
      performance with batch of dye and age of dye solution is also discussed.
      Additional experimental findings support the view that the orcein stain for
      elastic tissue and Shikata's modification produces consistent, high quality
      results as long as appropriate controls and suitable dye batches, e.g.,
      Biological Stain Commission certified dyes, are used.

PMID- 15473578
TI  - Traditional natural dyeing using crotal.

PMID- 15473579
TI  - Lichen purple--an annotated bibliography.
AB  - This bibliography lists and contains comments on publications describing the
      textile dyeing applications and organic chemistry of purple dyes derived from
      lichens. Elsewhere in this issue such colorants are termed orcein; the usage
      "lichen purple" reflects the historical emphasis of the work described. Note that
      commentary by CJC is placed after the bibliographic information in italics.

PMID- 15473580
TI  - Why fluorescent probes for endoplasmic reticulum are selective: an experimental
      and QSAR-modelling study.
AB  - The basis of the selectivity of fluorochromes routinely used to visualize the
      endoplasmic reticulum (ER) in live cells remains obscure. To clarify this,
      interactions of living cells with fluorochromes of varied physicochemical
      properties were analyzed experimentally and numerically using a quantitative
      structure activity relationship analysis (QSAR). Routine selective ER probes were
      found to be amphipathic, lipophilic cations with moderate-sized conjugated
      systems. The moderately lipophilic character permits probe uptake by passive
      diffusion without nonspecific accumulation in biomembranes. The moderately
      amphipathic character favors uptake into the ER, perhaps owing to its high
      concentration of zwitterionic lipid head-groups. The QSAR model rationalizes the
      impractical character of some ER probes mentioned in the literature, and could
      permit design of novel ER probes with different emission colors. The possibility
      of using the QSAR model as a tool to predict the accumulation of xenobiotics in
      the ER of living cells is illustrated by the localization of certain
      antipsychotic drugs in cultured cells.

PMID- 15473581
TI  - Acute and intermediate-term results of percutaneus left main coronary artery
      interventions.
AB  - BACKGROUND: Left main coronary artery disease is considered a surgical indication
      in most centers. However, in some cases prohibited from surgery or in patients
      with prior bypass grafting, there is a need for percutaneous coronary
      intervention in LMCA disease scenarios. OBJECTIVES: To assess the clinical
      outcomes among patients undergoing stent-based LMCA angioplasty. METHODS: We
      identified 34 consecutive patients who underwent PCI in LMCA at our institution.
      Procedural data and clinical outcomes were obtained for all patients. RESULTS:
      The mean age was 71 +/- 12 years. There were 27 elective and 7 emergent
      procedures performed on 23 "protected" LMCA and 11 "unprotected" LMCA. In
      emergent procedures, the prevalence of cardiogenic shock (29% vs. 0%, P = 0.04)
      in patients with prior coronary bypass (29% vs. 8.5%, P = 0.007) was
      significantly higher compared to elective cases. Procedural success in emergent
      procedures was significantly lower than in elective procedures (71 vs. 100%, P =
      0.04). In emergent versus elective procedures, the in-hospital mortality rate was
      higher (43 vs. 0%, P = 0.006). The rate of cumulative major adverse cardiac
      events at 1 and 6 months was 43% and 71% in emergent cases versus 0% and 33% in
      elective cases (P < 0.05 for both comparisons). In patients with "unprotected"
      LMCA the overall rate of major cardiac events at 1 month was higher compared to
      "protected" LMCA patients (27 vs. 0%, P = 0.02). Multivariate analysis revealed
      emergent procedure as an independent predictor for mortality and adverse cardiac
      events (odds ratio 6.7, 95% confidence interval 1.2-36; P = 0.02). CONCLUSIONS:
      Percutaneous interventions in LMCA are feasible and relatively safe in carefully
      selected cases. Procedural outcomes and clinical prognosis is highly dependent on
      the nature of disease prior to angioplasty (e.g., elective vs. emergent
      procedure) as well as on protection of the LMCA by patent grafts.

PMID- 15473582
TI  - Electronic medical record systems in Israel's public hospitals.
AB  - BACKGROUND: Various medical centers in Israel have recently incorporated
      electronic medical record systems. Knowing the EMR systems' features and pattern
      of use is an essential step for developing locally and nationally integrated
      systems. OBJECTIVES: To evaluate the status of EMR systems in all major general
      hospitals in Israel in terms of the applications used and the patterns of use.
      METHODS: Structured questionnaires were sent to hospital directors and directors
      of medical informatics units of 26 general and pediatric hospitals serving the
      vast majority of the population in Israel. The questionnaire included questions
      pertaining to the EMR systems, their usage, and the attitude of the participants
      to data security issues. RESULTS: Of the 26 general hospitals 23 (88.4%) returned
      the questionnaires. Of these, 21 (91.3%) use EMR systems. Twenty-seven different
      types of systems are in use in Israeli hospitals, and generally more than one
      type is used in a hospital. Physicians work with EMR systems in over 98% of the
      departments. Also, the EMR systems are used for clinical admission and discharge
      in over 90% of the departments and for medical daily follow-up in about 45%.
      CONCLUSIONS: Most of the hospitals in Israel use EMR systems but there is no
      standard data model. Physicians are the main users but the amount of data entered
      is still limited. Adoption of standards is essential for the integration of
      electronic patient records across Israeli healthcare organizations.

PMID- 15473583
TI  - Economic evaluation of an updated guideline for the empiric treatment of
      uncomplicated urinary tract infection in women.
AB  - BACKGROUND: Until recently trimethoprim-sulfamethoxazole was the drug recommended
      in the Leumit Health Fund for the empiric treatment of uncomplicated urinary
      tract infection in women. However, due to increased uropathogen resistance to
      this drug, the fund has designated nitrofurantoin as its new drug of choice.
      OBJECTIVES: To evaluate the potential economic impact of implementing this new
      pharmaco-policy. METHODS: Using data derived from the electronic patient records
      of the Leumit Health Fund, we identified all non-recurrent cases of women aged 18
      49 with a diagnosis of acute cystitis or UTI without risk factors for complicated
      UTI and empirically treated with antibiotics throughout 2003. The final sample
      comprised 5,489 physician-patient encounters. The proportion of cases treated
      with each individual drug was calculated, and the excess expenditure due to non
      adherence to the new guideline from the perspective of the health fund was
      evaluated using 5 days of therapy with nitrofurantoin as the reference treatment.
      RESULTS: Ofloxacin was the most frequently prescribed drug (30.24%), followed by
      TMP-SMX (22.43%), cephalexin (15.08%), and nitrofurantoin (12.59%). The observed
      net aggregate drug expenditure was 2.3 times greater than expected had all cases
      been treated with nitrofurantoin according to the guideline duration of 5 days.
      The cost of treatment in 53% of the cases exceeded the expected cost of the
      guideline therapy. CONCLUSIONS: Successful implementation of the new drug will
      likely improve quality of care and reduce costs to the health fund.

PMID- 15473584
TI  - Continence and quality of life assessment after artificial urinary sphincter
      implantation.
AB  - BACKGROUND: Sphincter-related incontinence after radical prostatectomy, benign
      prostatectomy or due to neurogenic disease has a considerable negative impact on
      quality of life. Artificial urinary sphincter implantation is a mainstay
      therapeutic option for these patients. OBJECTIVES: To assess patient
      satisfaction, subjective long-term continence and complications after AMS 800
      artificial urinary sphincter implantation. METHODS: The medical records of 34
      patients who underwent artificial urinary sphincter implantation for radical
      prostatectomy (n = 23), simple prostatectomy (n = 9) or neurogenic disease (n =
      2) between 1995 and 2003 were studied retrospectively. Median follow-up was 49
      months (range 3-102 months). Records were analyzed for urinary sphincter survival
      and complications. Quality of life and continence assessment was done by mailing
      an impact questionnaire. RESULTS: In 4 of the 34 patients (11.7%) the device was
      removed due to infection. One of the four had surgical revision elsewhere, and
      the other three were not interested in re-implantation of the device. Two
      patients (5.9%) underwent revisions due to mechanical failure. One patient died
      and three patients were not located. Twenty-seven out of a possible 30 patients
      (88%) completed the questionnaire; 22 (85%) achieved social continence (0-2 pads
      daily), and one patient had subjective difficulty activating the device.
      Subjective improvement and patient satisfaction was rated as 4.22 and 4.11,
      respectively (scale 0 to 5). CONCLUSIONS: Artificial urinary sphincter
      implantation is an efficacious option for sphincter-related incontinence. This
      study documents the positive impact of artificial urinary sphincter implantation
      on quality of life with acceptable complications; these results are comparable to
      other published studies.

PMID- 15473586
TI  - Pericarditis following permanent pacemaker insertion.
AB  - BACKGROUND: The appearance of pericarditis following insertion of a permanent
      pacemaker is not widely acknowledged in the literature. OBJECTIVES: To describe
      our experience with pericarditis following 395 permanent pacemaker implantations
      over 2 years. METHODS: We retrospectively reviewed the medical records of 395
      consecutive patients in whom new pacing systems or pacemaker leads had been
      implanted over a 2 year period. We searched the records for pericarditis that
      developed within 1 month after pacemaker implantation according to the ICD-9
      code. The incidence, clinical picture, response to treatment, and relationship to
      lead design and location were studied. RESULTS: Eight cases (2%) of pericarditis
      following implantation were detected. Clinical manifestations in all patients
      were similar to those of post-pericardiotomy syndrome and included chest pain (n
      = 7), friction rub (n = 1), fever (n = 2), fatigue (n = 2), pleural effusion (n =
      2), new atrial fibrillation (n = 2), elevated erythrocyte sedimentation rate (n =
      4), and echcardiographic evidence of pericardial effusion (n = 8). All affected
      patients had undergone active fixation (screw-in) lead implantation in the atrial
      position. The incidence of pericarditis with screw-in atrial leads was 3%
      compared to 0% in other cases (P < 0.05). CONCLUSIONS: Pericarditis is not
      uncommon following pacemaker implantation with active fixation atrial leads.
      Special attention should be paid to identifying pericardial complications
      following pacemaker implantation, especially when anticoagulant therapy is
      resumed or initiated. The use of passive fixation leads is likely to reduce the
      incidence of pericarditis but this issue should be further investigated.

PMID- 15473585
TI  - A phase I study of oral UFT given concomitantly with standard preoperative
      radiotherapy for rectal cancer.
AB  - BACKGROUND: Preoperative radiotherapy is standard treatment for rectal cancer and
      is often combined with 5-fluorouracil-based chemotherapy. UFT, a new oral 5FU
      derivative, given daily during a course of radiotherapy mimics the effect of
      continuous-infusion 5FU. OBJECTIVES: To determine the maximum tolerated dose of
      oral UFT and leucovorin with preoperative pelvic irradiation for rectal cancer,
      and assess tumor response. METHODS: In this phase 1 trial, 16 patients aged 42-79
      years with tumors within 12 cm of the anal verge received radiotherapy, 45 Gy
      over 5 weeks, an escalating dose of oral UFT, and a fixed dose of 30 mg/day
      leucovorin. UFT and leucovorin were given for 28 consecutive days concomitant
      with the first 4 weeks of radiotherapy. Surgery was scheduled for 4-6 weeks after
      completion of radiotherapy. The surgical procedure was determined by the surgeon
      at the time of surgery. RESULTS: No grade III toxicity was seen at 200 mg/m2/day
      UFT. Of eight patients who received 240 mg/m2/day UFT, one developed grade IV
      diarrhea; of four patients who received 270 mg/m2/day UFT, one was hospitalized
      with grade IV diarrhea and leukopenic fever and died during hospitalization. Of
      the 15 evaluable patients, 9 had pathologic tumor downstaging including 4
      patients with complete response. Only one patient required a colostomy.
      CONCLUSIONS: The MTD of UFT together with leucovorin and preoperative
      radiotherapy for rectal cancer is 240 mg/m2. The major toxicity was diarrhea.
      Downstaging was noted in 60% of patients, allowing sphincter-preserving surgery
      even in patients with low tumors.

PMID- 15473587
TI  - Post-stroke follow-up in a rehabilitation center outpatient clinic.
AB  - BACKGROUND: Follow-up examinations in a rehabilitation center clinic after stroke
      are essential for coordinating post-acute services and monitoring patient
      progress. Of first-stroke patients discharged from our rehabilitation ward to the
      community 92% are invited for ambulatory check-up once every 6 months.
      OBJECTIVES: To review patient complaints at follow-up and the recommendations
      issued by the attending physical medicine and rehabilitation specialist at the
      outpatient clinic. METHODS: We extracted relevant data from the records and
      assessed the relationship between functional status on admission and discharge
      (measured by FIM), length of stay, and number of complaints. Patients were
      divided according to the side of neurologic damage, etiology, whether the stroke
      was a first or recurrent event, and main clinical syndrome (neglect or aphasia).
      RESULTS: Patients' complaints included: decreased hand function (in 40%), general
      functional deterioration (20%), difficulty walking (11%), speech dysfunction
      (10%), various pains (especially in plegic shoulder) (8%), urine control (2%),
      sexual dysfunction (3%), swallowing difficulties (2%), and cognitive disturbances
      (2%). Patients received the following recommendations: physiotherapy (for 52.5%),
      occupational therapy (37.5%), speech therapy (12.5%), different bracing
      techniques (22.5%), pain clinic treatment (12.5%), changing medication
      prescriptions (7.5%), psychological treatment (10%), sexual rehabilitation (5%),
      vocational counseling (2.5%), counseling by social workers (2.5%), and repeat
      neuropsychological diagnosis (2.5%). A reverse correlation was found between the
      number of complaints and FIM at admission (P = 0.0001) and discharge (P =
      0.0003), and between LOS and FIM at admission (P = 0.0001) and discharge (P =
      0.004). A direct correlation was found between the number of complaints and LOS
      (P = 0.029). No relation was found between age, type of stroke, first and
      recurrent event, and clinical syndromes and patient complaints in the outpatient
      rehabilitation. Community rehabilitation services met 58% of all recommendations
      in 62% of patients, mainly physiotherapy and occupational therapy, with 34% of
      patients waiting for implementation of the recommendations and 4% not available
      for follow-up. CONCLUSIONS: Follow-up examinations should be an integral part of
      post-stroke rehabilitation. Rehabilitation treatment in the community must be
      strengthened.

PMID- 15473588
TI  - Hyperglycemia and acute ischemic stroke.

PMID- 15473589
TI  - Current dilemmas and future perspectives for breast cancer screening with a focus
      on optimization of magnetic resonance spectroscopic imaging by advances in signal
      processing.
AB  - Israel has a National Screening Program for early detection of breast cancer. The
      need to continue and even expand this program was recently stressed in light of
      the high risk in the population. However, the optimal modalities for breast
      cancer screening are controversial, especially for women at risk. Mammography,
      the established screening method, is critically examined, and molecular imaging
      techniques, such as magnetic resonance spectroscopy and spectroscopic imaging are
      explored, especially for primary breast cancer detection. MRS and MRSI are
      currently limited by their reliance on the conventional framework for data
      analysis in biomedical imaging, i.e., the fast Fourier transform. Recent
      mathematical advances in signal processing via the fast Pade transform can
      extract diagnostically important information, which until now has been
      unavailable with in vivo MRS. A clinical MRS signal illustrates the rapid and
      stable convergence provided by FPT, yielding accurate information about key
      metabolites and their concentrations at short acquisition times. We suggest that
      the next step would be to apply the FPT to in vivo MRS/MRSI signals from patients
      with breast cancer and to compare these to findings for normal breast tissue. The
      potential implications of such an optimized MRS/MRSI for breast cancer screening
      strategies are discussed, especially for younger women at high risk.

PMID- 15473590
TI  - Sentinel lymphadenectomy: an emerging new alternative for improving staging of
      early colorectal cancer.

PMID- 15473591
TI  - Left main coronary artery percutaneous intervention: are we there yet?

PMID- 15473592
TI  - Clinical guidelines as a tool for ensuring good clinical practice.

PMID- 15473593
TI  - Salvaging brain: new concepts in the management of acute stroke.

PMID- 15473594
TI  - Molecular defects of the growth hormone receptor gene, including a new mutation,
      in Laron syndrome patients in Israel: relationship between defects and ethnic
      groups.
AB  - BACKGROUND: Laron Syndrome, first described in Israel, is a form of dwarfism
      similar to isolated growth hormone deficiency caused by molecular defects in the
      GH receptor gene. OBJECTIVE: To characterize the molecular defects of the GH-R in
      Laron syndrome patients followed in our clinic. METHODS: Of the 63 patients in
      the cohort, we investigated 31 patients and 32 relatives belonging to several
      ethnic origins. Molecular analysis of the GH-R gene was performed using the
      single strand conformation polymorphism and DNA sequencing techniques. RESULTS:
      Eleven molecular defects including a novel mutation were found. Twenty-two
      patients carried mutations in the extracellular domain, one in the transmembrane
      domain, and 3 siblings with typical Laron syndrome presented a normal GH-R. Of
      interest are, on one hand, different mutations within the same ethnic groups: W
      15X and 5, 6 exon deletion in Jewish-Iraqis, and E180 splice and 5, 6 exon
      deletion in Jewish-Moroccans; and on the other hand, identical findings in
      patients from distinct regions: the 785-1 G to T mutation in an Israeli-Druze and
      a Peruvian patient. A polymorphism in exon 6, Gly168Gly, was found in 15
      probands. One typical Laron patient from Greece was heterozygous for R43X in exon
      4 and heterozygous for Gly168Gly. In addition, a novel mutation in exon 5:
      substitution of T to G replacing tyrosine 86 for aspartic acid (Y86D) is
      described. CONCLUSIONS: This study demonstrates: a) an increased focal incidence
      of Laron syndrome in different ethnic groups from our area with a high incidence
      of consanguinity; and b) a relationship between molecular defects of the GH-R,
      ethnic group and geographic area.

PMID- 15473595
TI  - Traumatic female urethral injury: an overlooked entity.

PMID- 15473596
TI  - Interstitial pneumonitis in a patient with melanoma treated with the high dose
      interferon alpha 2b regimen.

PMID- 15473597
TI  - Reflex sympathetic dystrophy after routine venipuncture.

PMID- 15473598
TI  - Postpartum acute kidney failure and hyponatremia: a clinical enigma.

PMID- 15473599
TI  - HRT 2004: where do we stand now? Pro.

PMID- 15473600
TI  - HRT 2004: Where do we stand now? Against.

PMID- 15473601
TI  - Mini Suffering State Examination (MSSE) Scale: first 5 years.

PMID- 15473602
TI  - Immunization saves lives.

PMID- 15473603
TI  - Birth seasonality in diabetic adults: reevaluation according to the age at
      disease onset.

PMID- 15473605
TI  - Pseudomembranous colitis.

PMID- 15473606
TI  - United in leadership--a meeting of minds.

PMID- 15473607
TI  - Guided by an Open Heart.

PMID- 15473608
TI  - Setting intentions for personal transformation.

PMID- 15473609
TI  - Quantum leadership isn't a quantum leap for holistic nurses.

PMID- 15473610
TI  - Lead and transform by joining AHNA's Legislative Task Force.

PMID- 15473611
TI  - Bulbo-spinal pathology and sudden respiratory infant death syndrome.

PMID- 15473612
TI  - Central venous catheter placement: comparison of the intravascular guidewire and
      the fluid column electrocardiograms.
AB  - BACKGROUND AND OBJECTIVE: Placement of central venous catheters in patients is
      associated with several risks including endocardial lesions and dysrhythmias.
      Correct positioning of central venous catheters in the superior vena cava is
      essential for immediate use. The objective of a first study was to evaluate the
      signal quality of an intravascular electrocardiogram (ECG) during position
      control using a guidewire compared with the customary fluid column-based ECG
      system, and to assess its efficacy of correct placement of the central venous
      catheter. A second study tested if dysrhythmias can be avoided by intravascular
      ECG monitoring during catheter and guidewire advancement. METHODS: The jugular or
      subclavian vein of 40 patients undergoing heart surgery or who were being treated
      in the intensive care unit was cannulated. Intravascular ECGs were recorded
      during position control, and guidewire and water column lead were compared in the
      same patient with regard to the quality of the ECG reading and P-wave
      enhancement. In another 40 patients, the guidewire was inserted only 10 cm and
      the central venous catheter advanced under guidewire ECG control. Correct
      position of all the central venous catheters was confirmed by chest radiography.
      RESULTS: All central venous catheters were correctly positioned in the superior
      vena cava. For the same catheter position, the P-wave was significantly larger in
      the guidewire ECG than in the fluid column system. No changes in the quality of
      the ECG were detected when the guidewire was advanced or withdrawn by 1 cm
      relative to the catheter tip. Cardiac dysrhythmias were not seen during ECG
      monitored advancement of the guidewire. CONCLUSIONS: ECG quality using a
      guidewire lead is superior to the water column-based system. Furthermore, it is
      independent from the exact position of the guidewire as related to the tip of the
      catheter. Using intravascular guidewire ECG during advancement can prevent
      induction of dysrhythmias.

PMID- 15473613
TI  - ECG-guided central venous catheter positioning: does it detect the pericardial
      reflection rather than the right atrium?
AB  - BACKGROUND AND OBJECTIVE: Although electrocardiography (ECG) guidance of central
      venous catheters (CVCs) is traditionally thought to detect the entrance into the
      right atrium (RA), there is little evidence in the literature to confirm this. We
      previously observed a high incidence of left-sided CVCs abutting the wall of the
      superior vena cava (SVC), even when the catheters were advanced past the point of
      increased P-wave amplitude. Our hypothesis was that this ECG amplitude signal is
      actually detecting the pericardial reflection rather than the RA. The goal of the
      study was to position catheter tips under ECG guidance outside the RA. METHODS:
      One-hundred central venous triple-lumen catheters inserted either via the right
      or the left internal jugular veins, respectively, were analysed in cardiac
      surgical patients. The position of the catheter tip was ascertained by ECG.
      METHOD A: A Seldinger guide-wire in the distal lumen served as exploring
      electrode, the respective insertion depth was recorded. METHOD B: The middle
      lumen (port opening 2.5 cm from the catheter tip, thus the catheter was advanced
      more towards the atrium) filled with a saline 10% fluid column served as the
      exploring electrode, and the insertion depth was recorded again. Descriptive data
      are given as mean+/-standard deviation. RESULTS: On average, the catheters were
      advanced by the expected 2+/-0.3 cm using Method B beyond the initial insertion
      by Method A. All 100 CVCs were finally correctly positioned in the SVC and
      confirmed by transoesophageal echocardiography. When chest radiography was
      performed after surgery not a single catheter abutted the lateral wall of the
      SVC. CONCLUSION: Since both methods detected the same structure, and catheters
      placed by Method B did not result in intra-atrial CVC tip position, the first
      increase in P-wave amplitude does correspond to a structure in the SVC, most
      likely the pericardial reflection.

PMID- 15473614
TI  - Outcome prediction in critical care: physicians' prognoses vs. scoring systems.
AB  - BACKGROUND AND OBJECTIVE: To compare the accuracy of prognoses made by intensive
      care physicians with the performance of two indicators, the original Simplified
      Acute Physiology Score (SAPS) II and a modified version optimized to the patient
      sample. METHODS: Data from 412 patients consecutively admitted to intensive care
      units of Gottingen University Hospital, Germany, were collected according to the
      original score criteria. Information necessary for the computation of SAPS II and
      the vital status on hospital discharge was recorded. To customize the original
      SAPS II in our cohort, the database was randomly divided into two subgroups.
      Logistic regression analysis with physiological values as explanatory variables
      was used. A bootstrap procedure completed the process. Furthermore, physicians
      were asked to indicate their prognostic judgement concerning the patients'
      hospital mortality. RESULTS: Discrimination analysis showed the following areas
      under receiver operating characteristic curves: physicians' prognoses 0.84
      (confidence interval (CI): 0.79-89), SAPS II 0.75 (CI: 0.69-0.80) and customized
      SAPS 0.72 (CI: 0.66-0.78). The physician's forecast was significantly better,
      while the customized and the original SAPS were not substantially different as
      regards their accuracy. CONCLUSIONS: Prognoses made by physicians are superior to
      objective models. This may result from more extensive knowledge and other kinds
      of information available to clinicians. A clinician's action also depends on
      his/her prognosis at the beginning of the treatment, giving raise to a possible
      correlation between medical outcome and the clinician's prognosis. Our findings
      indicate that physicians do not limit their prognosis to the objective factors at
      their disposal, but indicate that they base their decisions on experience and
      individual observations.

PMID- 15473615
TI  - Remifentanil provides better protection against noxious stimuli during cardiac
      surgery than alfentanil.
AB  - BACKGROUND AND OBJECTIVE: We hypothesized that remifentanil-propofol cardiac
      anaesthesia, plus administration of pirinitramide (piritramide) upon cessation of
      the remifentanil infusion, would be associated with a shorter time to tracheal
      extubation than alfentanil-propofol anaesthesia, without the occurrence of major
      haemodynamic instability. METHODS: Haemodynamic stability and recovery
      characteristics of two remifentanil infusion regimens (0.5 microg kg(-1)min(-1);
      0.25 microg kg(-1)min(-1)) were therefore compared with an alfentanil infusion
      regimen (1 microg kg(-1)min(-1)), in combination with target-controlled infusion
      of propofol, in a randomized blinded trial in 75 coronary artery surgery
      patients. RESULTS: Pirinitramide provided good postoperative analgesia without
      prolonging extubation times: median extubation time in minutes after stopping the
      opioid-sedative drugs was 300 in the higher-dose remifentanil group and 270 in
      the lower-dose remifentanil group and alfentanil group (P = 0.606). Significant
      time-by-treatment interactions were seen for systolic arterial pressure (P =
      0.015), mean arterial pressure (P = 0.009) and diastolic arterial pressure (P =
      0.006). No significant interaction (P = 0.489) and no constant treatment effect
      were seen for heart rate (P = 0.288). Time effects were highly significant (P <
      0.0001) for all haemodynamic variables. Heart rate remained stable in all groups.
      In the higher-dose remifentanil group, blood pressure was significantly different
      and lower during surgery and in this group less bolus doses of the opioid
      sedative drugs (P = 0.015) had to be given. CONCLUSION: The higher-dose
      remifentanil infusion provided superior suppression of haemodynamic responses to
      noxious stimuli with better haemodynamic stability.

PMID- 15473616
TI  - Evaluation of intensive care unit performance in Lithuania using the SAPS II
      system.
AB  - BACKGROUND AND OBJECTIVE: Outcome prediction and evaluation of intensive care
      unit (ICU) performance using severity of illness scoring is a tool for the
      estimation of effectiveness and quality of intensive care. We used the simplified
      acute physiology score (SAPS) II system to evaluate ICU performance. METHODS: The
      present study is a prospective observational study in an ICU at Vilnius
      University Emergency Hospital, Lithuania. The observed death rate was compared
      with the predicted death rate calculated using SAPS II system. The ability of the
      SAPS II prognostic system to predict the probability of hospital mortality was
      assessed with discrimination and calibration measures. RESULTS: Two-thousand-and
      sixty-seven patients consecutively admitted to the ICU were studied. The median
      SAPS II score on the first ICU day was 29. The SAPS II system showed a good
      ability to separate those patients predicted to live from those predicted to die
      (an area under the receiver operating characteristic curve was 0.883). The
      calibration curve demonstrated under-prediction of the actual death rate (Hosmer
      Lemeshow goodness-of-fit test, chi2 = 56.98; df = 8; P < 0.001). The observed
      mortality was higher than predicted by the SAPS II equation (observed to
      predicted ratio is 1.28). CONCLUSIONS: The SAPS II system is a useful tool for
      the assessment of ICU performance. This system demonstrated a good ability of
      discrimination, but an under-prediction of the actual mortality rate, in
      Lithuanian ICUs.

PMID- 15473617
TI  - New approach to an ovine model of hypodynamic endotoxaemia.
AB  - BACKGROUND AND OBJECTIVE: Since the moribund hypodynamic phase of septic shock
      has primarily been studied in small animal models, the objective of this study
      was to investigate the usefulness of infusing Salmonella typhosa endotoxin at
      incrementing doses to establish an ovine model of hypodynamic endotoxaemia.
      METHODS: In a prospective laboratory experiment, eight adult ewes were
      instrumented for a chronic study. Following a baseline measurement in the healthy
      state, a continuous endotoxin infusion was started with 10 ng kg(-1) min(-1) and
      was doubled every hour seven times. Haemodynamics, key variables of oxygen
      transport, and arterial lactate concentrations were determined every hour.
      RESULTS: In a dose-dependent manner, endotoxin infusion caused pulmonary
      hypertension, decreased cardiac output and mean arterial pressure, increased
      heart rate, and to a certain extent, systemic vascular resistance index.
      Following 4h of endotoxaemia, the maximum decrease in cardiac output occurred
      (4.8+/-0.2 vs. 7.6+/-0.3 Lmin(-1); P < 0.001). This was accompanied by tissue
      dysoxia, represented by decreases in oxygen delivery (797+/-20 vs. 1041+/-28
      mLmin(-1)), oxygen consumption (277+/-14 vs. 396+/-15 mLmin(-1)) and oxygen
      extraction rate (0.35+/-0.01 vs. 0.38+/-0.01%; each P < 0.01), as well as an
      increase in arterial lactate concentration (1.7+/-0.1 vs. 0.7+/-0.1 mmolL(-1); P
      < 0.05). CONCLUSIONS: This large animal model may be helpful to study the
      pathophysiology responsible for cardiovascular failure, and also new therapeutic
      approaches relevant to management of hypodynamic circulation in the common
      setting of progressed systemic inflammation.

PMID- 15473618
TI  - Pulse dye densitometry using indigo carmine is useful for cardiac output
      measurement, but not for circulating blood volume measurement.
AB  - BACKGROUND AND OBJECTIVE: We evaluated the validity of a newly developed pulse
      dye densitometer for indigo carmine for measuring cardiac output and circulating
      blood volume. METHODS: Measurements of cardiac output and circulating blood
      volume were performed with the indigo carmine densitometer during normovolaemia,
      hypovolaemia and hypervolaemia in nine mongrel dogs under general anaesthesia.
      The validity was evaluated by comparison of the values of cardiac output and
      circulating blood volume obtained by the thermodilution technique and the 51Cr
      labelled red blood cell method, respectively. We also examined indigo carmine
      removal by continuous veno-venous haemofiltration after indigo carmine injection.
      RESULTS: There was good agreement between dye densitometer- and thermodilution
      derived cardiac output (r = 0.885, P < 0.001). The bias and limits of agreement
      of these values were 0.09 and+/-1.07 L min(-1) (2 SD, n 22), respectively. The
      dye-densitometer-derived circulating blood volume was greater than that of the
      51Cr-labelled red blood cell method, and both values showed weak agreement (r =
      0.587, P < 0.027). The sieving coefficient of indigo carmine through continuous
      veno-venous haemofiltration was 0.34+/-0.06. CONCLUSIONS: These data indicate
      that indigo carmine densitometry is a reliable method for cardiac output
      determination, but it overestimates circulating blood volume, probably due to the
      transition of indigo carmine into the extravascular space in the systemic
      circulation.

PMID- 15473619
TI  - Exposure of personnel to sevoflurane during paediatric anaesthesia: influence of
      professional role and anaesthetic procedure.
AB  - BACKGROUND AND OBJECTIVE: This study was performed to determine the individual
      exposure of paediatric operating theatre personnel to sevoflurane and to evaluate
      the impact of inhalation induction and various airway approaches on exposure to
      airborne sevoflurane. METHODS: Mean individual environmental (workplace air)
      exposure to sevoflurane and a biomarker of exposure (urinary sevoflurane) were
      monitored in 36 subjects (10 anaesthetists, 10 surgeons, 12 nurses and 4
      auxiliary personnel) working in two paediatric operating rooms. RESULTS:
      Environmental and urinary values were significantly greater in anaesthetists
      compared with other groups, with median values of 0.65ppm (interquartile range
      1.36; 95th percentile 4.36) for breathing zone sevoflurane and 2.1 microgL(-1)
      urine (interquartile range 2.6; 95th percentile 7.6) for urinary sevoflurane.
      Anaesthetists exceeded the 2ppm maximum allowed environmental concentration
      recommended by the National Institute for Occupational Safety and Health in 4 of
      22 cases (18.1%). A positive correlation was found between the number of patients
      undergoing inhalational induction each day and mean values of breathing zone and
      urinary sevoflurane. An increase in the number of daily laryngeal mask
      insertions, or the use of rigid bronchoscopy, are statistically related to higher
      environmental and urinary values (P < 0.01 and <0.00001 for breathing zone
      sevoflurane, P < 0.05 and <0.01 for urinary sevoflurane, respectively).
      CONCLUSIONS: Anaesthesia with sevoflurane can pose a hazard of chronic exposure
      with anaesthetists having the highest risk. Endotracheal intubation offers
      considerable protection against exposure. Routine anaesthesia using a standard
      facemask, a laryngeal mask or rigid bronchoscopy are risk factors for increased
      anaesthetic exposure.

PMID- 15473620
TI  - Abnormalities of contrast sensitivity and electroretinogram following sevoflurane
      anaesthesia.
AB  - BACKGROUND AND OBJECTIVE: We tested the hypothesis that disturbances of the
      visual pathway following sevoflurane general anaesthesia (a) exist and persist
      even after clinical discharge criteria have been met and (b) are associated with
      decreased contrast sensitivity. METHODS: We performed pattern and full-field
      flash electroretinograms (ERG) in 10 unpremedicated ASA I patients who underwent
      nitrous oxide/sevoflurane anaesthesia. ERG and contrast sensitivity were recorded
      preoperatively, immediately after discharge from the recovery room and 2 h after
      discontinuation of sevoflurane. The time at which the Post Anaesthesia Discharge
      Score first exceeded 9 was also noted. Data were analysed using paired, one
      tailed t-tests and Pearson's correlation coefficient. RESULTS: On the full-field
      photopic ERG, b-wave latency was greater at each postoperative time point (31.6+/
      1.1 and 30.8+/-1.1 ms) compared to preoperatively (30.1+/-1.1 ms, P < 0.001 and P
      = 0.03, respectively). Oscillatory potential latencies were greater on discharge
      from the recovery room compared with preanaesthetic values (23.1+/-3.1 vs. 22.4+/
      3.3 ms, P = 0.01) and returned to baseline by 2 h after emergence from
      anaesthesia. Also at 2 h after emergence from anaesthesia: (a) P50 latency on the
      pattern ERG was greater than at baseline (81.5+/-17.9 vs. 51.15+/-22.6ms, P =
      0.004); (b) N95 amplitude was less compared to preanaesthetic values (2.6+/-0.5
      vs. 3.3+/-0.4 microV, P = 0.003) and (c) contrast sensitivity was less compared
      to baseline values (349+/-153 vs. 404+/-140, P = 0.048). A positive correlation
      was demonstrated between contrast sensitivity and both N95 amplitude and b-wave
      latency (r = 0.99 and r = -0.55 at significance levels of P < 0.005 and P < 0.05,
      respectively). CONCLUSIONS: Postoperative ERG abnormalities and associated
      decreases in contrast sensitivity are consistently present in patients who have
      undergone nitrous oxide/sevoflurane anaesthesia. These abnormalities persist
      beyond the time at which standard clinical discharge criteria have been met.

PMID- 15473621
TI  - Is intraperitoneal levobupivacaine with epinephrine useful for analgesia
      following laparoscopic cholecystectomy? A randomized controlled trial.
AB  - BACKGROUND AND OBJECTIVE: A randomized controlled trial of patients undergoing
      laparoscopic cholecystectomy. To evaluate whether the instillation of
      levobupivacaine, with epinephrine, intraperitoneally, reduces morphine
      consumption; further, to consider the degree of abdominal and shoulder pain in
      the presence of local anaesthetic at the site of surgical incision. METHODS:
      Patients received a standardized procedure and were allocated randomly to receive
      either (a) 2.5 mg mL(-1) levobupivacaine 30 mL, with epinephrine 5 microg mL(-1),
      or (b) normal saline 30 mL, with epinephrine 5 microg mL(-1), to the bed of the
      gall bladder and above the liver, immediately before wound closure. RESULTS:
      Median (interquartile range) total abdominal pain during inspiration in the
      levobupivacaine group was significantly (P = 0.041) lower (71 (21-129) mm) than
      that in the placebo group (123 (71-179) mm). However, there was no significant
      difference between the two groups with respect to total abdominal pain at rest,
      right shoulder pain or the consumption of rescue morphine and rescue
      dihydrocodeine. There were no differences between the two groups with respect to
      the administration of cyclizine, total nausea and total sedation scores. In
      addition, the number of episodes of vomiting was not significantly different.
      CONCLUSIONS: Intraperitoneal administration of levobupivacaine with epinephrine
      is associated with modest analgesia following laparoscopic cholecystectomy.

PMID- 15473622
TI  - The analgesic and sedative effects of intrathecal midazolam in perianal surgery.
AB  - BACKGROUND AND OBJECTIVE: Our purpose was to evaluate the analgesic and sedative
      effects of intrathecal midazolam when added to spinal bupivacaine in patients
      undergoing perianal surgery under spinal anaesthesia. METHODS: Forty-four
      patients were randomly allocated into two equal groups: Group I (B) received
      hyperbaric bupivacaine 0.5% 2 mL + saline 0.9% 1 mL in a total volume of 3 mL
      intrathecally; Group II (BM) received hyperbaric bupivacaine 0.5% 2 mL + 1 mL of
      2mg preservative-free midazolam in a total volume of 3 mL intrathecally. In both
      groups, the onset and recovery times of sensory block, the degree and recovery
      times of motor block as well as the sedation and visual analogue pain scores were
      recorded, and statistically compared. RESULTS: In Group BM, the postoperative
      visual analogue pain scores were significantly lower at the first 4 h (P < 0.05),
      the average time until the first dose of additional analgesic requirement was
      significantly longer (P < 0.05), and sedation scales were significantly higher (P
      < 0.05), compared to Group B. There were no statistically significant differences
      in the onset and the full recovery times of sensory and motor blocks in the two
      groups. CONCLUSION: The use of intrathecal midazolam combined with intrathecal
      bupivacaine produces a more effective and longer analgesia with a mild sedative
      effect in perianal surgery.

PMID- 15473623
TI  - Keratoconjunctival injury in the prone position: a prospective study in
      neurosurgical patients.

PMID- 15473624
TI  - Eye protection during general anaesthesia: comparison of four different methods.

PMID- 15473625
TI  - The new PA(Xpress) airway device during mechanical ventilation in anaesthetized
      patients: a prospective, randomized comparison with the laryngeal mask airway.

PMID- 15473626
TI  - Syringomyelia, neuropathic pain and Caesarean section.

PMID- 15473627
TI  - Inadvertent epidural administration of cisatracurium.

PMID- 15473628
TI  - Laterality and imbalance of muscle stiffness relate to personality.
AB  - The authors' purpose in this study was to test the hypothesis that laterality and
      imbalance of muscle stiffness relate to personality. The authors selected 23
      healthy volunteers and divided them into two groups based on the predominance of
      muscle stiffness on the left or right side. Imbalance of muscle stiffness was
      calculated as the absolute value of the difference of muscle stiffness between
      the right and left sides. The authors evaluated personality with the Japanese
      version of the Eysenck Personality Questionnaire. Subjects with left predominant
      muscle stiffness of the rectal abdominis had significantly higher neuroticism
      score than those with right predominant muscle stiffness. Subjects with more
      imbalance of muscle stiffness in the latissimus dorsi and in the trapezius had
      significantly higher neuroticism and psychoticism scores than those with less
      imbalance. The findings suggest that laterality and imbalance of muscle stiffness
      relate to personality.

PMID- 15473629
TI  - Stress, social support, and cortisol: inverse associations?
AB  - An association between stress and health has been hypothesized. However, the
      association pathways are unclear. In this article, the authors examined the
      associations between stress, social support, and cortisol and the mediating
      effect of several psychosocial variables. Adult men and women (n = 146) completed
      psychosocial surveys and provided saliva samples for cortisol assessments,
      quarterly, for 1 year Cross-sectional analysis results showed an inverse
      relationship between basal cortisol and stress (Model 1: coefficient = -.068, SE
      = .024, p = .006). After controlling for stress, the authors also found an
      inverse relationship between basal cortisol and social support among individuals
      with high social support (upper tertile compared with 1st and 2nd tertiles)
      (Model 2: coefficient = -.440, SE = .155, p = .005). Longitudinal models showed
      similar findings for both associations. These findings do not support the general
      hypothesis of a negative effect of chronic intermittent stress on health through
      Hypothalamic Pituitary Adrenal (HPA) axis activation, but do support a positive
      effect of social support on the HPA axis. Both findings deserve further
      investigation.

PMID- 15473630
TI  - The Revised-Perceived Illness Experience Scale (R-PIE): data from the Barretstown
      studies.
AB  - The Perceived Illness Experience Scale (PIE) was developed to measure children's
      perception of their illness experience. In this article, the authors examine the
      previously uninvestigated factor structure of the PIE using the responses of 184
      European children (mean age = 11.61 years, SD = 2.31) with life-threatening
      illnesses. The findings showed a 6-factor solution: (1) School/Peer Rejection,
      (2) Thinking About Illness, (3) Physical Appearance, (4) Interference With
      Activity, (5) Parental Responses, and (6) Manipulation. Children's mean scores on
      each subscale and for the composite Revised PIE (R-PIE) were generally low,
      suggesting that as a group, children do not perceive that their illness has an
      especially negative impact on their lives. There were differences between the
      children's mean scores on some subscales depending on their gender nationality
      grouping, and type of illness. These findings provide empirical support for the R
      PIE and suggest its usefulness in measuring children's experience of different
      illnesses in multinational settings.

PMID- 15473631
TI  - The interrelationship of psychosocial risk factors for coronary artery disease in
      a working population: do we measure distinct or overlapping psychological
      concepts?
AB  - There is growing evidence that psychosocial factors contribute to the risk of
      coronary artery disease. Commonly used psychometric scales share several features
      leading to questions about whether they reflect distinguishable concepts. Study
      participants were 822 employees of the Augsburg Cohort Study (mean age 40 years,
      89% men). The authors analyzed the interrelationship between the following
      psychosocial measures by applying Pearson correlations and factor analysis to the
      Hospital Anxiety and Depression Scale (HADS), Type D Personality (DS14), the
      Maastricht Vital Exhaustion Questionnaire (VE), Social Support (F-SozU), the SF12
      Health Survey, and Effort-Reward Imbalance. Although the full correlation matrix
      revealed low to medium associations supporting the notion that the applied
      psychometric scales show some conceptual overlap, factor analyses resulted in 13
      distinguishable and interpretable factors, considerably reflecting the original
      psychometric scales. This strengthens the assumption that the psychometric scales
      used constitute distinct psychological concepts, in particular, depressive
      symptomatology and negative affectivity versus vital exhaustion.

PMID- 15473632
TI  - Residues and half-lives of pyrethrins on field-grown pepper and tomato.
AB  - The dried flower heads of Tanacetum cinerariifolium Trev. (Family: Compositae)
      contain insecticidal compounds collectively called "pyrethrins." Pyrethrins are
      the subject of intense interest for use in crop protection because their
      toxicological properties permit control of certain insect species at application
      rates as low as 5-10 g AI acre(-1). Seedlings of sweet pepper, Capsicum annuum L.
      cv. Bell Boy Hybrid and tomato, Lycopersicon esculentum Mill. cv. Mountain Spring
      F1 Hybrid were planted and sprayed with a Multi-Purpose Insecticide formulation
      that contains 0.2% pyrethrins, 1.0% piperonyl butoxide (PBO), 88% diatomaceous
      earth, and 10.8% inert ingredients. The formulation was sprayed on pepper and
      tomato foliage when tomato fruits became red ripe and pepper became mature green
      at the rate of 6 lbs of formulated product per acre (5.4 and 27.2 g AI of
      pyrethrins and PBO, respectively). Following spraying, pepper and tomato leaves
      and fruits were collected at different time intervals for residue analysis using
      a high performance liquid chromatograph (HPLC) equipped with a UV detector.
      Residues of pyrethrins and PBO were generally higher on the leaves than fruits.
      Initial deposits (1 h following spraying) of pyrethrins were significantly higher
      on pepper than tomato fruits. Half-life (T1/2) values on pepper and tomato fruits
      did not exceed 2 h. Where concern exists over synthetic pesticide residues on
      treated crops and in the environment, pyrethrins are suitable alternatives that
      can be used to reduce the risk of exposure to synthetic pesticide residues.

PMID- 15473633
TI  - Persistence, distribution, and emission of Telone C35 injected into a Florida
      sandy soil as affected by moisture, organic matter, and plastic film cover.
AB  - With the phase-out of methyl bromide scheduled for 2005, alternative fumigants
      are being sought. This study of Telone C35, a mixture of (Z)- and (E)-1,3
      dichloropropene (1,3-D) with chloropicirin (CP), focuses on its emissions,
      distribution, and persistence in Florida sandy soil in microplots with different
      soil-water and organic matter carbon (C) content with and without two different
      plastic film mulches. The addition of CP did not affect the physical behavior of
      the isomers of 1,3-D. Slower subsurface dispersion and longer residence time of
      the mixed fumigant occurred at higher water content. An increase in the percent
      organic carbon in the soil led to a more rapid decrease for chloropicirin than
      for 1,3-dichloropene isomers. The use of a virtually impermeable film (VIF) for
      soil cover provided a more even distribution and longer persistence under all the
      conditions studied in comparison to polyethylene (PE) film cover or no cover. The
      conditions of near field capacity water content, low organic matter, and a
      virtually impermeable film cover yielded optimum conditions for the distribution,
      emission control, and persistence of Telone C35 in a Florida sandy soil.

PMID- 15473634
TI  - Dissipation of chlorpyrifos in two soil environments of semi-arid India.
AB  - The dissipation of chlorpyrifos (20 EC) at environment-friendly doses in the
      sandy loam and loamy sand soils of two semi-arid fields and the presence of
      pesticide residues in the harvested groundnut seeds, were monitored. The movement
      of chlorpyrifos through soil and its binding in the loamy sand soil was studied
      using 14C chlorpyrifos. Chlorpyrifos was moderately stable in both loamy sand and
      sandy loam soils, with half-life of 12.3 and 16.4 days, respectively. With 20 EC
      treatments the dissipation was slower for standing crop than seed treatment,
      indicative of the high degradation rates in the bioactive rhizosphere. In soil,
      3,5,6-trichloro-2-pyridinol (TCP) was the principal breakdown product. Presence
      of 3,5,6-trichloro-2-methoxypyridine (TMP), the secondary metabolite, detected in
      the rhizospheric samples during this study, has not been reported earlier in
      field soils. The rapid dissipation of the insecticide from the soil post
      application might have resulted from low sorption due to the alkalinity of the
      soil and its low organic matter content, fast topsoil dissipation possibly by
      volatilization and photochemical degradation, aided by the low water solubility,
      limited vertical mobility due to confinement of residues to the upper 15 cm soil
      layers and microbial mineralization and nucleophilic hydrolysis. Contrary to the
      reports of relatively greater mobility of its metabolites in temperate soils, TMP
      and TCP remained confined to the top 15 cm soil. The formation of bound residues
      (half-life 13.4 days) in the loamy sand soil was little and not "irreversible." A
      decline in bound residues could be correlated to decreasing TCP concentration.
      Higher pod yields were obtained from pesticide treated soils in comparison to
      controls. Post-harvest no pesticide residues were detected in the soils and
      groundnut seeds.

PMID- 15473635
TI  - Metabolism of the nonylphenol isomer [ring-U-14C]-4-(3',5'-dimethyl-3'-heptyl)
      phenol by cell suspension cultures of Agrostemma githago and soybean.
AB  - The biotransformation of the nonylphenol isomer [ring-U-14C]-4-(3',5'-dimethyl-3'
      heptyl)-phenol (4-353-NP, consisting of two diastereomers) was studied in soybean
      and Agrostemma githago cell suspension cultures. With the A. githago cells, a
      batch two-liquid-phase system (medium/n-hexadecane 200:1, v/v) was used, in order
      to produce higher concentrations and amounts of 4-353-NP metabolites for their
      identification; 4-353-NP was applied via the n-hexadecane phase. Initial
      concentrations of [14C]-4-353-NP were 1 mg L(-1) (soybean), and 5 and 10 mg L(-1)
      (A. githago). After 2 (soybean) and 7 days (A. githago) of incubation, the
      applied 4-353-NP was transformed almost completely by both plant species to four
      types of products: glycosides of parent 4-353-NP, glycosides of primary 4-353-NP
      metabolites, nonextractable residues and unknown, possibly polymeric materials
      detected in the media. The latter two products emerged especially in soybean
      cultures. Portions of primary metabolites amounted to 19-22% (soybean) and 21-42%
      of applied 14C (A. githago). After liberation from their glycosides, the primary
      4-353-NP metabolites formed by A. githago were isolated by HPLC and examined by
      GC-EIMS as trimethylsilyl derivatives. In the chromatograms, eight peaks were
      detected which due to their mass spectra, could be traced back to 4-353-NP. Seven
      of the compounds were side-chain monohydroxylated 4-353-NP metabolites, while the
      remaining was a (side-chain) carboxylic acid derivative. Unequivocal
      identification of the sites of hydroxylation/oxidation of all transformation
      products was not possible. The main primary metabolites produced by A. githago
      were supposed to be four diastereomers of 6'-hydroxy-4-353-NP (about 80% of all
      products identified). It was concluded that plants contribute to the
      environmental degradation of the xenoestrogen nonylphenol; the toxicological
      properties of side-chain hydroxylated nonylphenols remain to be examined.

PMID- 15473636
TI  - Methidathion complexes with homoionic and surfactant-modified montmorillonites.
AB  - The formation of the insecticide methidathion (S-[(5-methoxy-2-oxo-1,3,4
      thiadiazol-3(2H)-yl)methyl] O,O-dimethyl phosphorodithioate) complexes with
      inorganic cation-saturated (Mg2+, Ca2+, Cu2+, and Ni2+) montmorillonites was
      investigated. The nature and structure of the complexes was determined by X-ray
      diffraction and infrared spectroscopy. The arrangement of the pesticide molecule
      in the interlayer space was also considered from ab initio calculations using
      simpler related molecules. The insecticide methidathion penetrated the interlayer
      spaces of the homoionic clay samples. The ligand-cation interactions in these
      complexes depend on the nature and characteristics of the saturating cations.
      Mechanisms involving water bridges and direct coordination with the exchange
      cation were proposed for the adsorption of methidathion by inorganic cation
      saturated montmorillonites. The effect of the inorganic cations on the sorption
      of the cationic surfactant tetradecyltrimethylammonium bromide (TDTMA) by
      montmorillonite was also studied and the subsequent sorption of methidathion in
      TDTMA+-Montmorillonite determined. Van der Waals bonds constitute the
      methidathion adsorption mechanism by montmorillonite saturated with TDTMA+. The
      arrangements of methidathion and of the cationic surfactant molecules in the
      montmorillonite interlayer space were demonstrated.

PMID- 15473637
TI  - Surfactant-enhanced release of carbaryl and ethion from two long-term
      contaminated soils.
AB  - The potential of five nonionic surfactants, Triton X-100, Brij35, Ethylan GE08,
      Ethylan CD127, and Ethylan CPG660 for enhancing release of carbaryl and ethion
      from two long-term contaminated soils was evaluated using the batch method.
      Incorporation of the surfactants into soils enhanced the release of both
      pesticides to various extents, which could be related to the type of pesticides
      and type and the amount of surfactants added. Release of ethion was dramatically
      enhanced by aqueous concentrations of surfactants above their critical micelle
      concentration values. This was attributed to solubility enhancement through
      incorporation of the highly hydrophobic compound within surfactant micelles. A
      concentration of 10 g L(-1) of various surfactants released >70% of the total
      ethion from the soil irrespective of the surfactant. For carbaryl, the
      surfactants were effective at low concentrations and dependence on concentration
      was lower than in the case of ethion. The ethylan surfactants (GE08, CD127, and
      CPG660) had a higher potential than Triton X-100 and Brij35 for releasing the
      pesticides. However, there was still a significant portion of carbaryl (11% of
      the total) and ethion (17% of the total) left in the soil. Our study also showed
      that there must be an optimal concentration of each surfactant to maximize the
      mass transfer of pesticides. At some threshold concentration level, additional
      surfactant started to inhibit the mass transfer of solute from the soil into the
      water. The results suggested that surfactants could help remediation of soils
      polluted by pesticides. The choice of surfactant should be made based on the
      properties of pesticides.

PMID- 15473638
TI  - Electrochemical monitoring of methylparathion degradation in an acid aqueous
      medium in presence of Cu(II).
AB  - A study was undertaken to determine the effect of Cu(II) in degradation of
      methylparathion (o,o-dimethyl o,4-nitrophenyl phosphoriotioate) in acid medium.
      Initial electrochemical characterization of Cu(II) and methylparathion was done
      in an aqueous medium at a pH range of 2-7. Cu(II) was studied in the presence of
      different anions and it was observed that its electroactivity depends on pH and
      is independent of the anion used. Methylparathion had two reduction signals at pH
      < or = 6 and only one at pH > 6. The pesticide's transformation kinetic was then
      studied in the presence of Cu(II) in acid buffered aqueous medium at pH values of
      2, 4, and 7. Paranitrophenol appeared as the only electroactive product at all
      three pH values. The reaction was first order and had k values of 5.2 x 10(-3) s(
      1) at pH 2, 5.5 x 10(-3) s(-1) at pH 4 and 9.0 x 10(-3) s(-1) at pH 7. It is
      concluded that the principal degradation pathway of methylparathion in acid
      medium is a Cu(II) catalyzed hydrolysis reaction.

PMID- 15473639
TI  - Sorption kinetics of atrazine and diuron in soils from southern Brazil.
AB  - Sorption kinetics of atrazine and diuron was evaluated in soil samples from a
      typical landscape in Parana. Samples were collected (0-20 cm) in a no-tillage
      area from Mambore, PR, which has been cultivated under a crop rotation for the
      last six years. Six sampling points of the slope were selected to represent a
      wide range of soil chemical and physical properties found in this area.
      Radiolabeled tracers (14C-atrazine and 14C-diuron) were used and the
      radioactivity was detected by liquid scintillation counting (LSC). Sorption was
      accomplished for increasing equilibration periods (0.5, 1.5, 3, 6, 12, 24, and 48
      h). Kinetics data fitted adequately well to Elovich equation, providing evidences
      that soil reaction occurs in two distinct stages: a fast, initial one followed by
      a slower one. During the fast phase, 34-42 and 71-79% of total atrazine and
      diuron applied were sorbed to soil samples. No important differences were found
      among combinations of soil and herbicide sorption during the slow phase. The
      unrealistic conditions under batch experiments should be overestimating sorption
      in the fast phase and underestimating diffusion in the slow phase. Sorption of
      both herbicides was positively correlated to organic carbon and clay contents of
      soils, but atrazine was much less sorbed than diuron, showing its higher
      potential to contaminate groundwater, specially in sandy, low organic carbon
      soils.

PMID- 15473641
TI  - PeLM: modeling of pesticide-losses through runoff and sediment transport.
AB  - A GIS-aided pesticide loss model (PeLM) was developed to simulate pesticide
      losses through surface runoff and sediment transport in watershed systems. The
      PeLM could tackle the movement of eroded soil along with surface runoff as well
      as the pesticide losses in adsorbed and dissolved phases. The contributions of
      different soil types in the sediment were also examined. The model was applied to
      the Kintore Creek Watershed of southern Ontario, Canada. The simulation results
      were verified through observed data, indicating a correlation level of 0.89-0.98.
      The results also showed that clay particles usually held the largest share of
      contributions to pesticide losses through soil erosion. This study is significant
      in the efforts for modeling nonpoint source pollution in watershed systems. It
      provides useful information and support for the related decisions of watershed
      management.

PMID- 15473640
TI  - Sorption of the fumigant 1,3-dichloropropene on soil.
AB  - The fumigant 1,3-dichloropropene (1,3-D) is considered a major replacement to
      methyl bromide, which is to be phased out of use in the United States by 2005.
      The main purpose of this study was to evaluate soil-water partitioning of 1,3-D
      in two California agricultural soils (Salinas clay loam and Arlington sandy
      loam). The partition coefficients (Kd and Kf) were determined by directly
      measuring the concentration of 1,3-D in the solid phase (Cs) and aqueous phase
      (Cw) after batch equilibration. In the Salinas clay loam, the Kf of cis-1,3-D in
      adsorption and desorption isotherms was 0.47 and 0.54, respectively, with
      respective values of 0.39 and 0.49 for trans-1,3-D. This slight hysteric effect
      suggests that a different range of forces are involved in the adsorption and
      desorption process. Since n was near unity in the Freundlich equation, the
      Freundlich isotherms can also be approximated using the liner isotherm. At 25
      degrees C, the Kd of the 1,3-D isomers in both soils ranged from 0.46 to 0.56,
      and the Koc (organic matter partition coefficient) ranged from 58 to 70. The
      relatively low Kd values and a Koc that falls within the range of 50-150,
      suggests that 1,3-D is weakly sorbed and highly mobile in these soils.
      Understanding the sorption behavior of 1,3-D in soil is important when developing
      fumigation practices to reduce the movement of 1,3-D to the air and groundwater.

PMID- 15473642
TI  - Chemical valorization of forest and agricultural by-products. Obtention, chemical
      characteristics, and mechanical behavior of a novel family of hydrophobic films.
AB  - Esterification of hemicelluloses of the xylan family was performed in order to
      produce hydrophobic films. Acylation reactions were carried out with lauroyl
      chloride in the N,N-dimethylacetamide/lithium chloride homogeneous system using 4
      dimethylaminopyridine as activator and were induced by microwave irradiation. In
      the experimental conditions used, 108 and 172% mass ratios were obtained for the
      dodecyl-grafted xylan and heteroxylan, respectively. The degrees of substitution
      (DS) were 1.3 (maximum 2) for xylan and 1.2 (maximum 2.1) for heteroxylan. These
      products were further characterized by FT-IR spectroscopy. The mechanical and
      thermomechanical behavior of this new family of hydrophobic films were analyzed
      and compared to those obtained from cellulose with a similar DS by the means of
      tensile tests. Our results indicate that the dodecyl-grafted xylan film presents
      the best rigidity-resistance to traction ratio.

PMID- 15473643
TI  - A protocol to select high quality datasets of ecotoxicity values for pesticides.
AB  - The key to any QSAR model is the underlying dataset. In order to construct a
      reliable dataset to develop a QSAR model for pesticide toxicity, we have derived
      a protocol to critically evaluate the quality of the underlying data. In
      developing an appropriate protocol that would enable data to be selected in
      constructing a QSAR, we concentrated on one toxicity end point, the 96 h LC50
      from the acute rainbow trout study. This end point is key in pesticide regulation
      carried out under 91/414/EEC. The dataset used for this exercise was from the US
      EPA-OPP database.

PMID- 15473644
TI  - Degradation of metolachlor in crude extract of Aspergillus flavus.
AB  - Crude enzyme from a soil fungus, Aspergillus flavus, was isolated from a field
      soil following repeated applications of metolachlor [2-Chloro-N-(methoxy-1
      methylethyl)-2'-ethyl-6'-methyl acetanilide]. Metolachlor hydrolysis by the crude
      enzyme extract was determined by enzyme assay. The tests were performed in
      phosphate buffer, pH 7.5, and the reaction was carried out at two herbicide
      concentrations (20 and 100 microg mL(-1)) and two crude extract volumes (0.2 and
      0.5 mL of the homogenized crude extract mixture). The rate of metolachlor
      degradation was found faster in samples containing higher volume of crude
      extract, (T(1/2), 5.7 h) for both concentrations of the herbicide. The activities
      of enzymes responsible for dechlorination coupled with hydroxylation, N
      dealkylation, and breaking of amide linkage were found responsible in the
      degradation.

PMID- 15473645
TI  - MSMA resistance studies.
AB  - Monosodium methanearsonate (MSMA)-resistant and -susceptible common cocklebur
      (Xanthium strumarium L.) and cotton (Gossypium hirsutum L.) were treated with
      MSMA. Plant parameters analyzed were: glutathione synthetase activity, selected
      amino acid (arginine, glutamic acid, alanine, citrulline, glutamine, and
      glutathione) content and arsenic content (MSMA, total arsenic, and arsonate). No
      reduction of arsenic from the parent pentavalent form present in MSMA to the
      trivalent form was detected. Arginine, glutamic acid, and glutamine content
      increased in tissue three days after MSMA treatment. Glutathione content
      decreased during the first three days after treatment; however, five days after
      treatment the resistant biotype of cocklebur and cotton had elevated glutathione
      levels (8-20 times greater, respectively). Glutathione Synthetase activity was
      higher in cotton than in either of the cocklebur biotypes; MSMA did not affect
      its activity in cotton or either cocklebur biotype. Resistant biotypes have a
      slightly higher activity than the susceptible biotype. Tolerance of cotton to
      MSMA may be related to glutathione synthetase activity and possibly to the
      presence of phytochelatins. Also, increased glutathione levels in the resistant
      biotype may implicate phytochelatin involvement in the resistance mechanism.

PMID- 15473646
TI  - Genotypic differences in effects of cadmium exposure on plant growth and contents
      of cadmium and elements in 14 cultivars of bai cai.
AB  - Fourteen cultivars of bai cai (Brassica campestris L. ssp. chinensis var.
      communis) were grown in the nutrient solutions containing 0-0.5 microg mL(-1) of
      cadmium (Cd) to investigate genotypic differences in the effects of Cd exposure
      on the plant growth and uptake and distribution of Cd in bai cai plants. The Cd
      exposure significantly reduced the dry and fresh weights of roots and shoots, the
      dry weight ratio of shoot/root (S/R), total biomass, and chlorophyll content
      (SPAD value). Cd concentrations in bai cai ranged from 13.3 to 74.9 microg g(-1)
      DW in shoots and from 163.1 to 574.7 microg g(-1) DW in roots under Cd exposure,
      respectively. The considerable genotypic differences of Cd concentrations and
      accumulations in both shoots and roots were observed among 14 bai cai cultivars.
      Moreover, Cd mainly accumulated in the roots. Cd also caused the changes of
      uptake and distribution of nutrients in bai cai and under the influence of
      cadmium, the concentration of potassium (K) decreased in shoot and increased in
      root. However, the concentrations of magnesium (Mg), phosphorus (P), manganese
      (Mn), boron (B), and iron (Fe) increased in shoots and decreased in roots. In
      addition, Cd exposure resulted in an increase in calcium (Ca), sulphur (S), and
      zinc (Zn) concentrations in both shoots and roots but had no significant effects
      on the whole uptake of the examined mineral nutrients except for S.

PMID- 15473647
TI  - Anti-cancer effect of liriodenine on human lung cancer cells.
AB  - Our previous work demonstrated that liriodenine, an isoquinoline alkaloid
      isolated from plant species of many genera, exhibits a potent cytotoxic effect on
      various types of human cancer cells. In this study, we investigated the effect of
      liriodenine on the growth and viability of human lung cancer cells and addressed
      the underlying mechanism of action. We found that liriodenine suppressed
      proliferation of A549 human lung adenocarcinoma cells in a dose- and time
      dependent manner. Flow cytometric analysis showed that liriodenine blocked cell
      cycle progression at the G2/M phase. Induction of G2/M arrest by liriodenine was
      accompanied by reduction of G1 cyclin (D1) and accumulation of G2 cyclin (B1). In
      vitro kinase activity assay demonstrated that the enzymatic activity of the
      cyclin B1/cyclin-dependent kinase 1 complex was reduced in liriodenine-treated
      cells. More importantly, incubation with liriodenine led to activation of
      caspases and apoptosis in A549 cells. The apoptosis-inducing activity of
      liriodenine was more apparent when cells were cultured under serum-free
      conditions. Our results indicate that liriodenine exerts potent anti
      proliferative and apoptosis-inducing effects on human lung cancer cells.

PMID- 15473648
TI  - Relationship between post-stroke depression and lesion location: a meta-analysis.
AB  - Our understanding of the relationship between the neuroanatomic loci of brain
      damage and the incidence of post-stroke depression (PSD) is not complete. Many
      studies have investigated this relationship and the evidence is conflicting. With
      the purpose of gaining a consistent, strong, and credible conclusion on the
      relationship between PSD and the loci of brain damage, a meta-analysis was used
      in this study to systematically reanalyze the findings of related studies and to
      investigate the sources of heterogeneity among study results. The key words
      "stroke or cerebrovascular" and "depression or mood or affective" were entered
      into the MEDLINE, PsycINFO, and EMBASE databases to search for relevant studies.
      The references cited in the studies found were also used to locate additional
      studies. For each eligible study, the important study characteristics were
      recorded, and the effect sizes of the relationship between PSD and lesion
      location were computed. Furthermore, we conducted subgroup analyses to explore
      the heterogeneity among study results. A total of 3,668 patients participating in
      52 studies were included in this meta-analysis. There was a weak relationship
      between PSD and right hemisphere lesion. The major sources of heterogeneous study
      results included systematic exclusion of patients with language dysfunction and
      use of different assessors and instruments for diagnosing depression. Future
      efforts should aim to enhance standards for reporting studies, improve assessment
      tools for assessing depression of aphasic patients, and adopt appropriate study
      methodologies for investigating the relationship between PSD and lesion location.

PMID- 15473650
TI  - Applying theory of planned behavior to predict nurses' intention and volunteering
      to care for SARS patients in southern Taiwan.
AB  - Severe acute respiratory syndrome (SARS) spread worldwide after an outbreak in
      Guangdong Province, China, in mid-November 2002. Health care workers were at
      highest risk of infection. The purpose of this study, which was based on Ajzen's
      theory of planned behavior (TPB), was to determine the extent to which personal
      attitudes, subjective norms, and perceived control influence nurses' intention
      and volunteering to care for SARS patients. After the SARS outbreak, a total of
      750 staff nurses (response rate 90%) at one hospital completed a questionnaire
      assessing their intention to provide care to SARS patients. Overall, 42.7% of
      nurses had a positive intention to provide care to SARS patients, and 25.4% of
      nurses would volunteer to care for SARS patients. Four factors explaining 35% of
      the variance in nurses' intention to care for SARS patients were self-efficacy
      (beta = 0.39, p < 0.001), attitude (beta = 0.25, p < 0.001), years of working in
      the study hospital (beta = -0.15, p < 0.001), and receiving resources from the
      hospital (beta = 0.13, p < 0.001). Two factors explaining 15% of the variance in
      nurses' volunteering to care for SARS patients were intention (beta = 0.31, p <
      0.001) and attitude (beta = 0.15, p < 0.001). The final model shows that the
      variables of the TPB contributed significantly to the explanation of a portion of
      variance in nurses' intention and volunteering to care for SARS patients. The
      results are helpful for human resources managers facing a new contagious disease.

PMID- 15473649
TI  - Posterior reversible encephalopathy syndrome: magnetic resonance imaging and
      diffusion-weighted imaging in 12 cases.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a potentially devastating
      neurologic syndrome, but timely treatment may lead to complete reversal of the
      disease course. We reviewed 12 cases of PRES and describe the clinical history
      and imaging findings, including conventional magnetic resonance imaging (MRI),
      diffusion-weighted imaging (DWI), and calculated apparent diffusion coefficient
      (ADC) maps, used to establish the diagnosis of PRES. Three male and nine female
      patients aged between 11 and 70 years (mean, 37 years) with clinical and imaging
      findings consistent with PRES were enrolled in the study. All patients had
      undergone conventional MRI and 10 had undergone additional DWI studies. Ten
      patients had follow-up MRI studies. DWI was performed using a 1.5T system with a
      single-shot spin-echo echoplanar pulse sequence. Initial and follow-up
      neuroimaging and clinical history were reviewed. Lesions were almost always
      present over the posterior circulation, mainly the parieto-occipital region,
      affecting primarily the white matter. The anterior circulation region, brainstem,
      cerebellum, deep cerebral white matter, and thalamus were also involved in five
      cases. Conventional MRI revealed hyperintensity on T2-weighted and fluid
      attenuated inversion recovery images. DWI showed isointensity and increased
      signal intensity on ADC values in all cases, indicating vasogenic edema. Clinical
      and MRI follow-up showed that the symptoms and radiologic abnormalities could be
      reversed after appropriate treatment of the causes of PRES in most patients (9 of
      10). In one patient, the ADC value was lower on follow-up images, indicating
      cytotoxic edema with ischemic infarct. DWI was a useful complement to MRI in the
      diagnosis of PRES.

PMID- 15473651
TI  - Coronary artery aneurysms in a young patient with acute myocardial infarction: a
      case report.
AB  - Coronary artery aneurysms are not uncommon. They are usually arteriosclerotic in
      origin, and may be congenital or secondary to injury, dissection, infection,
      inflammation, or Kawasaki disease (KD). Herein, we report a case involving a 25
      year-old male smoker with acute myocardial infarction (AMI). Coronary angiography
      showed triple-vessel disease, coronary artery aneurysms, and diffuse ectasia.
      Coronary artery bypass grafting was performed without complications. Based on his
      history, serologic examinations, and angiographic findings, we suspected that his
      coronary artery aneurysms and ectasia were the adult sequelae of KD. This case is
      a good reminder that KD victims may suffer from young-onset AMI.

PMID- 15473652
TI  - Acute idiopathic syringomyelia: a case report.
AB  - There have been isolated reports in the literature of the natural history and
      less than complete knowledge of the epidemiology and pathophysiology of
      syringomyelia. This article describes a clinically acute-onset abnormal patient
      with localized dilatation of the central canal of the spinal cord who had no
      evidence of present or prior Chiari's malformation, trauma, infection, tumor, or
      other predisposing pathologic condition. It is suggested that this distinct
      condition be labeled "acute idiopathic syringomyelia".

PMID- 15473653
TI  - Sialolipoma of the floor of the mouth: a case report.
AB  - Intra-oral lipoma is a well-known entity, but lipomatous tumors including
      salivary gland tissue containing clustered or peripherally located ducts and
      acinar cells are uncommon. They are a newly recognized entity of salivary gland
      lipoma, designated sialolipoma. We describe a case of sialolipoma arising in the
      floor of the mouth presenting with apparently normal salivary gland tissue, as
      demonstrated by both histologic and immunohistochemical findings, in a 67-year
      old female. Complete surgical removal of the tumor with preservation of the
      sublingual gland was implemented after a careful examination confirming that the
      lesion did not originate from the sublingual gland.

PMID- 15473654
TI  - Interdisciplinary management of dental implant patient: a case report.
AB  - Maxillary molars can over-erupt when their antagonists are lost and there are no
      replacements. When the opposing molars severely extrude into the edentulous
      space, it is difficult to replace the missing teeth with either fixed or
      removable prostheses. We present the following case report, providing a solution
      for this type of problem. A two-stage posterior subapical osteotomy was used to
      reestablish the intermaxillary space. Following orthodontic treatment and implant
      placement, the patient regained occlusal harmony and normal masticatory function.

PMID- 15473655
TI  - Synthesis and antimicrobial activity of novel tetrahydrobenzothienopyrimidines.
AB  - Due to the rapidly growing number of resistant strains of bacteria, the search
      for antibacterial agents with new modes of action will always remain an important
      and challenging task. Thus, the reaction of 2-substituted or unsubstituted-4-(4
      acetylanilino)-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidine derivatives 1-3
      with the hydrazine derivatives, semi and/or thiosemicarbazides, provided the
      corresponding hydrazones 4-6 and semi and/or thiosemicarbazones 7-9. Claisen
      Schmidt condensation of compounds 1 or 2 with the appropriate aldehyde yielded
      the chalcones 10, 11 which, when treated with hydroxylamine hydrochloride gave
      rise to the isoxazoline-containing compounds 12, 13. Furthermore, reacting the
      respective chalcones 10, 11 with different hydrazines, urea and/or thiourea,
      furnished compounds 14, 15, 16, and 17 respectively. Representative compounds
      were tested for their antimicrobial activity against Candida albicans and certain
      gram-positive and gram-negative bacteria. Their MICs were then determined.
      Compound 15e, showed a broad spectrum of activity while most of the other
      compounds showed varying antimicrobial activity.

PMID- 15473656
TI  - Synthesis and evaluation of antitumor activity of 2- and 6-[(1,3-benzothiazol-2
      yl)aminomethyl]-5,8-dimethoxy-1,4-naphthoquinone derivatives.
AB  - 2- or 6-substituted BZT-N derivatives were synthesized, and their cytotoxic
      activity against cancer L1210 and SNU-1 cells was examined. The antitumor action
      was also assessed in mice bearing S-180 cells in peritoneal cavity. In a
      comparison, it was found that 6-substituted BZT-N derivatives exhibited higher
      potencies in both bioactivities than 2-substituted BZT-N derivatives against
      L1210 cells in in vitro and S-180 in vitro tests exception of compound 36.
      Interestingly, it was observed that 2-substituted compound 36, which has methyl
      group at R1 position, exhibited a better antitumor activity than 6-substituted
      compounds against L1210 and SNU-1 in vitro. The ED50 value of 2-substituted
      compound 36 against L1210 was found to be comparable to the ED50 value of
      adriamycin and was even better against the solid cancer cell line SNU-1. It was
      also observed that 2-substituted compound 36 showed better antitumor activity in
      mice bearing S-180 cells in the peritoneal cavity. The T/C (%) value of 2
      substituted compound 36 was similar to that of adriamycin. Quantitative structure
      activity relationship (QSAR) tests reveal that the experimental ED50 values
      against SNU-1 closely correlate with both the calculated HOMO energies (E(HOMO))
      and the measured 1H-NMR chemical shift of 3-H (deltaH). The results suggests that
      a compound having higher E(HOMO) and deltaH values usually should have a lower
      ED50 (SNU-1) value.

PMID- 15473657
TI  - Determination of tiapride in human plasma using hydrophilic interaction liquid
      chromatography-tandem mass spectrometry.
AB  - A rapid, sensitive and selective hydrophilic interaction liquid chromatography
      tandem mass spectrometric (HILIC-MS/MS) method for the determination of tiapride
      in human plasma was developed. Tiapride and internal standard, metoclopramide
      were extracted from human plasma with dichloromethane at basic pH and analyzed on
      an Atlantis HILIC silica column with the mobile phase of acetonitrile-ammonium
      formate (190 mM, pH 3.0) (94:6, v/v). The analytes were detected using an
      electrospray ionization tandem mass spectrometry in the multiple-reaction
      monitoring mode. The standard curve was linear (r=0.999) over the concentration
      range of 1.00-200 ng/mL. The coefficient of variation and relative error for
      intra- and interassay at three QC levels were 6.4-8.8% and -2.0-3.6%,
      respectively. The recoveries of tiapride ranged from 96.3 to 97.4%, with that of
      metoclopramide (internal standard) being 94.2%. The lower limit of quantification
      for tiapride was 1.00 ng/mL using 100 microL of plasma sample.

PMID- 15473658
TI  - Establishment of in vitro test system for the evaluation of the estrogenic
      activities of natural products.
AB  - In order to evaluate estrogenic compounds in natural products, an in vitro
      detection system was established. For this system, the human breast cancer cell
      line MCF7 was stably transfected using an estrogen responsive chloramphenicol
      acetyltransferase (CAT) reporter plasmid yielding MCF7/pDsCAT-ERE119-Ad2MLP
      cells. To test the estrogenic responsiveness of this in vitro assay system,
      MCF7/pDsCAT-ERE119-Ad2MLP cells were treated with various concentrations of
      17beta-estradiol. Treatments of 10(-8) to 10(-12) M 17beta-estradiol revealed
      significant concentration dependent estrogenic activities compared with ethanol.
      We used in vitro assay system to detect estrogenic effects in Puerariae radix and
      Ginseng radix Rubra extracts. Treatment of 500 and 50 microg/ml of Puerariae
      radix extracts increased the transcriptional activity approximately 4- and 1.5
      fold, respectively, compared with the ethanol treatment. Treatment of 500, 50,
      and 5 microg/ml of Ginseng radix Rubra extracts increased the transcriptional
      activity approximately 3.2-, 2.7-, and 1.4-fold, respectively, compared with the
      ethanol treatment. These observations suggest that Puerariae radix and Ginseng
      radix Rubra extracts have effective estrogenic actions and that they could be
      developed as estrogenic supplements.

PMID- 15473659
TI  - A benzenoid from the stem of Acanthopanax senticosus.
AB  - Seven compounds were isolated from the stem of Acanthopanax senticosus by
      repeated column chromatography. Their structures were elucidated as isovanillin
      (1), (-)-sesamin (2), isofraxidin (3), (+)-syringaresinol (4), 5
      hydroxymethylfurfural (5), eleutheroside B (6), and eleutheroside E (7) by
      spectral analysis. Among them, isovanillin (1) was isolated for the first time
      from the family Araliaceae.

PMID- 15473660
TI  - Pulsatilla saponin D: the antitumor principle from Pulsatilla koreana.
AB  - By bioassay-guided separation, an already known saponin, Pulsatilla saponin D was
      isolated from the root of Pulsatilla koreana Nakai as a antitumor component when
      evaluated by in vivo antitumor activity as well as in vitro cytotoxic activity
      test. It showed potent inhibition rate of tumor growth (IR, 82%) at the dose of
      6.4 mg/kg on the BDF1 mice bearing LLC cells.

PMID- 15473661
TI  - Induction of the anticarcinogenic marker enzyme, quinone reductase, by Dalbergiae
      Lignum.
AB  - The effect of an extract of Dalbergiae Lignum and four components that were
      isolated from the extract on the anticarcinogenic phase II marker enzyme, quinone
      reductase (QR), was investigated. Of the solvent extracts of Dalbergiae Lignum,
      the CH2Cl2 fraction was the most potent in inducing QR activity, with a CD value
      (the concentration required to double the QR activity) of 29.5 microg/mL. The
      CH2Cl2 extract was further separated into six compounds, four of which were
      identified as 4-methoxydalbergione, latifolin, 4',6-dihydroxy-7-methoxyflavanone,
      and obtusafuran. Obtusafuran [CD = 1.1 microM; chemopreventive index (CI) =
      101.9] and latifolin (CD = 1.7 microM; CI = 154.6) displayed potent QR inducing
      activity and high chemopreventive indices. Latifolin and 4-methoxydalbergione
      were identified as strong DPPH-scavengers with half-maximal free radical
      scavenging concentrations of 15.9 and 17.2 microM, respectively.

PMID- 15473662
TI  - Stylopine from Chelidonium majus inhibits LPS-induced inflammatory mediators in
      RAW 264.7 cells.
AB  - Stylopine is a major component of the leaf of Chelidonium majus L.
      (Papaveraceae), which has been used for the removal of warts, papillomas and
      condylomas, as well as the treatment of liver disease, in oriental countries.
      Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but
      concentration-dependently reduced nitric oxide (NO), prostaglandin E2 (PGE2),
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the
      IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS
      stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2
      protein expressions were markedly suppressed by stylopine in a concentration
      dependent manner. These results suggest that stylopine suppress the NO and PGE2
      production in macrophages by inhibiting the iNOS and COX-2 expressions. These
      biological activities of stylopine may contribute to the anti-inflammatory
      activity of Chelidonium majus.

PMID- 15473663
TI  - Neuroprotective effect of wogonin: potential roles of inflammatory cytokines.
AB  - Wogonin (5,7-dihydroxy-8-methoxyflavone), an active component originated from the
      root of Scutellaria baicalensis Georgi, has been reported to possess antioxidant
      and anti-inflammatory properties. In this study, we investigated the
      neuroprotective effect of wogonin in a focal cerebral ischemia rat model. Wogonin
      markedly reduced the infarct volume after 2 h middle cerebral artery occlusion
      followed by 22 h reperfusion. Wogonin decreased the production of nitric oxide
      and inflammatory cytokines such as TNF-alpha and IL-6 in lipopolisaccharide
      stimulated microglial cells. While wogonin reduced the activity of NF-kappaB, it
      did not change the activity of mitogen-activated protein kinases family members,
      p38, ERK and JNK. The lipopolisaccharide-stimulated production of NO and
      cytokines was significantly blocked by various kinds of NF-kappaB inhibitors such
      as N-acetyl cysteine, pyrrolidinedithiocarbamate and MG-132. The data may
      indicate that wogonin has neuroprotective effect by preventing the overactivation
      of microglial cells, possibly by inactivating NF-kappaB signaling pathway.

PMID- 15473664
TI  - Inhibition of nitric oxide production from lipopolysaccharide-treated RAW 264.7
      cells by synthetic flavones: structure-activity relationship and action
      mechanism.
AB  - Recent investigations have shown that certain flavonoids, especially flavone
      derivatives, inhibit nitric oxide (NO) production by inducible NO synthase (iNOS)
      in macrophages, which contribute their anti-inflammatory action. For the purpose
      of finding the optimized chemical structures of flavonoids that inhibit NO
      production, various A- and B-ring substituted flavones were synthesized and
      evaluated for their inhibitory activity using lipopolysaccharide-treated RAW
      264.7 cells. It was found that the optimal chemical structures were A-ring 5,7
      dihydroxyflavones having the B-ring 2',3'-dihydroxy or 3',4'-dihydroxy or 3',4'
      hydroxy/methoxy (methoxy/hydroxy) groups. These structurally optimized compounds
      were revealed to be down-regulators of iNOS induction, but not direct iNOS
      inhibitors. Of these derivatives that were evaluated, 2',3',5,7
      tetrahydroxyflavone and 3',4',5,7-tetrahydroxyflavone (luteolin) showed the
      strongest inhibition. The IC50 values for these compounds were 19.7 and 17.1
      microM, respectively. Therefore, these compounds may have a potential as new anti
      inflammatory agents.

PMID- 15473665
TI  - An isocoumarin with hepatoprotective activity in Hep G2 and primary hepatocytes
      from Agrimonia pilosa.
AB  - Phytochemical investigation of the aqueous extract of the roots of Agrimonia
      pilosa Ledeb. (Rosaceae), as guided by hepatoprotective activity in vitro,
      furnished two isocoumarins, agrimonolide (1) and agrimonolide 6-O-beta-D
      glucoside (3), and (+)-catechin (2). Compound 1 showed hepatoprotective effects
      on both tacrine-induced cytotoxicity in human liver-derived Hep G2 cells and tert
      butyl hydroperoxide-induced cytotoxicity in rat primary hepatocytes with EC50
      values of 88.2 +/- 2.8 and 37.7 +/- 1.6 microM, respectively.

PMID- 15473666
TI  - Alaternin and emodin with hydroxyl radical inhibitory and/or scavenging
      activities and hepatoprotective activity on tacrine-induced cytotoxicity in HepG2
      cells.
AB  - The antioxidative and hepatoprotective potentials of two anthraquinones,
      alaternin (2-hydroxyemodin) and emodin, to scavenge and/or inhibit hydroxyl
      radicals generated by the Fenton reaction and to protect tacrine-induced
      cytotoxicity in human liver derived HepG2 cells were evaluated, respectively. The
      inhibitory activity on hydroxyl radical generated in a cell-free chemical system
      (FeSO4/H2O2) was investigated by a fluorescence spectrophotometer using a highly
      fluorescent probe, 2',7'-dichlorofluorescein. The hydroxyl radical scavenging
      activity was determined by electron spin resonance spectroscopy using 5,5-dimethy
      1-pyrroline-N-oxide as hydroxyl radicals trapping agents. Tacrine-induced HepG2
      cell toxicity was determined by a 3-[4,5-dimethylthiazole-2yl]-2,5
      diphenyltertrazolium bromide assay. Although the scavenging activity of alaternin
      on hydroxyl radical was similar to that of emodin in dose-dependent patterns, the
      inhibitory activity exhibited by the former on hydroxyl radical generation was
      stronger than that of the latter, with IC50 values of 3.05 +/- 0.26 microM and
      13.29 +/- 3.20 microM, respectively. In addition, the two anthraquinones,
      alaternin and emodin showed their hepatoprotective activities on tacrine-induced
      cytotoxicity, and the EC50 values were 4.02 microM and 2.37 microM, respectively.
      Silymarin, an antihepatotoxic agent used as a positive control exhibited the EC50
      value of 2.00 microM. These results demonstrated that both alaternin and emodin
      had the simultaneous antioxidant and hepatoprotective activities.

PMID- 15473667
TI  - Potential role of ursodeoxycholic acid in suppression of nuclear factor kappa B
      in microglial cell line (BV-2).
AB  - Expression of the NF-kappaB-dependent genes responsible for inflammation, such as
      TNF-alpha, IL-1beta, and nitric oxide synthase (NOS), contributes to chronic
      inflammation which is a major cause of neurodegenerative diseases (i.e.
      Alzheimer's disease). Although NF-kappaB plays a biphasic role in different cells
      like neurons and microglia, controlling the activation of NF-kappaB is important
      for its negative feedback in either activation or inactivation. In this study, we
      found that ursodeoxycholic acid (UDCA) inhibited IkappaB alpha degradation to
      block expression of the NF-kappaB-dependent genes in microglia when activated by
      beta-amyloid peptide (A beta). We also showed that when microglia is activated by
      A beta42, the expression of A20 is suppressed. These findings place A20 in the
      category of "protective" genes, protecting cells from pro-inflammatory
      repertoires induced in response to inflammatory stimuli in activated microglia
      via NF-kappaB activation. In light of the gene and proteins for NF-kappaB
      dependent gene and inactivator for NF-kappaB (IkappaB alpha), the observations
      now reported suggest that UDCA plays a role in supporting the attenuation of the
      production of pro-inflammatory cytokines and NO via inactivation of NF-kappaB.
      Moreover, an NF-kappaB inhibitor such as A20 can collaborate and at least enhance
      the anti-inflammatory effect in microglia, thus giving a potent benefit for the
      treatment of neurodegenerative diseases such as AD.

PMID- 15473669
TI  - Determination of the kinetic properties of platycodin D for the inhibition of
      pancreatic lipase using a 1,2-diglyceride-based colorimetric assay.
AB  - A 1,2-diglyceride-based multi-step colorimetric assay to measure the pancreatic
      lipase activity was applied for the determination of the kinetic profiles of the
      lipase inhibition with a slight modification and the validity verification. With
      this assay method, our study revealed that platycodin D, one of major
      constituents of Platycodi Radix, inhibits the pancreatic lipase activity in a
      competitive type, with the value of KI being 0.18+/-0.02 mM. In addition, PD has
      affected the values of K(m,app) and Kcat/Km in a dose-dependent manner. The
      results shed a meaningful light on how PD mediates lipid metabolism in the
      intestinal tracts. On the other hand, since the revised assay is sensitive,
      rapid, and does not affect the accuracy to the kinetic properties, it is
      applicable not only to evaluation of the kinetic properties of the pancreatic
      lipase, but also to high-throughput screening of pancreatic lipase activity.

PMID- 15473668
TI  - Site-specific 99mTc-labeling of antibody using dihydrazinophthalazine (DHZ)
      conjugation to Fc region of heavy chain.
AB  - The development of an antibody labeling method with 99mTc is important for cancer
      imaging. Most bifunctional chelate methods for 99mTc labeling of antibody
      incorporate a 99mTc chelator through a linkage to lysine residue. In the present
      study, a novel site-specific 99mTc labeling method at carbohydrate side chain in
      the Fc region of 2 antibodies (T101 and rabbit anti-human serum albumin antibody
      (RPAb)) using dihydrazinophthalazine (DHZ) which has 2 hydrazino groups was
      developed. The antibodies were oxidized with sodium periodate to produce aldehyde
      on the Fc region. Then, one hydrazine group of DHZ was conjugated with an
      aldehyde group of antibody through the formation of a hydrazone. The other
      hydrazine group was used for labeling with 99mTc. The number of conjugated DHZ
      was 1.7 per antibody. 99mTc labeling efficiency was 46-85% for T101 and 67-87%
      for RPAb. Indirect labeling with DHZ conjugated antibodies showed higher
      stability than direct labeling with reduced antibodies. High immunoreactivities
      were conserved for both indirectly and directly labeled antibodies. A
      biodistribution study found high blood activity related to directly labeled T101
      at early time point as well as low liver activity due to indirectly labeled T101
      at later time point. However, these findings do not affect practical use. No
      significantly different biodistribution was observed in the other organs. The
      research concluded that DHZ can be used as a site-specific bifunctional chelating
      agent for labeling antibody with 99mTc. Moreover, 99mTc labeled antibody via DHZ
      was found to have excellent chemical and biological properties for nuclear
      medicine imaging.

PMID- 15473670
TI  - Enantioselective pharmacokinetics of carvedilol in human volunteers.
AB  - Carvedilol is administered as a racemic mixture of the R(+)- and S(-)
      enantiomers, although they exhibit different pharmacological effects. To
      investigate the stereoselective pharmacokinetics, the enantiomeric separation of
      carvedilol in human plasma was undertaken using capillary electrophoresis (CE).
      Resolution of the enantiomers was achieved using 2-hydoxypropyl-beta-cyclodextrin
      as the chiral selector. Phosphate buffer (50 mM, pH 4.0) containing 10 mM of 2
      hydoxypropropyl-beta-cyclodextrin was used as electrolytic buffer. Achiral
      separation was carried out with the same electrolytic buffer without chiral
      selector. Following a single oral administration of 25-mg carvedilol to 11
      healthy, male volunteers, stereoselective pharmacokinetic analysis was
      undertaken. The maximum plasma concentrations (Cmax) were 48.9 and 21.6 ng/mL for
      (R)-carvedilol and (S)-carvedilol, respectively, determined by the chiral method.
      The profiles of the plasma concentration of (RS)-carvedilol showed Cmax of 71.5,
      72.2, and 73.5 ng/mL, as determined by the CE, HPLC/FD methods and calculations
      from the data of the chiral method, respectively.

PMID- 15473671
TI  - Effect of glycyrrhizic acid on protein binding of diltiazem, verapamil, and
      nifedipine.
AB  - The effects of glycyrrhizic acid (GLZ) on protein binding of diltiazem,
      verapamil, and nifedipine were investigated. Protein binding studies (human
      serum, human serum albumin (HSA) and alpha1-acid glycoprotein (AAG)) were
      conducted using the equilibrium dialysis method with and without addition of GLZ.
      The binding parameters, such as the number of moles of bound drug per mole of
      protein, the number of binding sites per protein molecule, and the association
      constant, were estimated using the Scatchard plot. The serum binding of
      nifedipine, verapamil, and diltiazem was displaced with addition of GLZ, and the
      decreases of Ks for serum were observed. GLZ decreased the association constants
      of three drugs for HSA and AAG, while the binding capacity remained similar with
      addition of GLZ. Although the characteristics of interaction were not clear, GLZ
      seemed to mainly affect HSA binding of nifedipine rather than AAG binding, while
      GLZ seemed to affect both AAG- and HSA-bindings of verapamil and diltiazem
      resulting in a serum binding displacement.

PMID- 15473672
TI  - Innovations in locking plate technology.
AB  - Plating techniques remain the mainstay for managing most periarticular and
      selected long bone fractures. However, movement toward more biologically
      appropriate plating techniques is occurring in an attempt to minimize soft-tissue
      stripping, decrease the need for bone grafting, and improve union rates. Internal
      fixation with locking plates creates a toggle-free, fixed-angle construct. Early
      data on the biomechanical and clinical performance of these implants are
      encouraging. Current indications for locked plating include periarticular
      fractures, typically those with metaphyseal comminution. Although impressive
      union rates have been reported, malunion remains a concern, especially when
      percutaneous techniques are used. Further clinical and biomechanical research on
      locking plate technology is needed to define its place fully alongside existing
      technology in orthopaedic trauma.

PMID- 15473673
TI  - Analgesic pharmacology: I. Neurophysiology.
AB  - The transmission of a pain signal from the periphery to the central nervous
      system is complex and only partially understood. Tissue damage results in
      peripheral release of endogenous chemicals that can directly activate nociceptive
      afferent fibers, sensitize nociceptors, or cause increased local extravasation
      and vasodilatation. These algesiogenic substances may be found in local tissues,
      plasma, and nerve terminals. Release of these substances may be caused by
      mechanical injury, radiation, or heat, or release may be stimulated by the by
      products of tissue injury (ie, catecholamines or collagen). Peripheral
      nociceptors may be further sensitized by repeated noxious stimuli. Nociceptive
      afferents have their neurons in the dorsal root ganglion and contact second-order
      neurons in the dorsal horn or, less often, in the medulla. Modulation of the pain
      signal in the dorsal horn involves local inhibitory and facilitatory interneurons
      as well as diverse excitatory and inhibitory neurotransmitters. The neuronal
      circuitry in the dorsal horn can change and modulate with time so that pain
      signals sometimes long outlast the original peripheral tissue injury. This
      central sensitization is thought to be mediated largely through the NMDA receptor
      complex.

PMID- 15473674
TI  - Analgesic pharmacology: II. Specific analgesics.
AB  - Methods of treatment are different for acute and chronic pain. For acute pain,
      analgesics such as nonsteroidal anti-inflammatory drugs and opiates are commonly
      used, sometimes combined with regional anesthesia, such as peripheral nerve block
      or peridural local anesthesia. The mechanism of transition from an acute to a
      chronic pain state is poorly understood. Only NMDA receptor antagonists and
      epidural morphine have shown relatively consistent results as preemptive
      analgesics. Agents more successfully used to manage chronic pain include those
      that modify the neurochemistry of the spinal cord dorsal horn, such as tricyclic
      antidepressants, anticonvulsants, gamma-amino butyric acid agonists, local
      anesthetic analogs, and NMDA antagonists. Opiates may be used chronically, but
      tolerance and lack of efficacy may then develop. In selected patients with
      refractory chronic pain, centrally administered analgesics may be considered,
      including opiates, dilute local anesthetic, NMDA receptor antagonists, clonidine,
      midazolam, baclofen, or calcium channel blockers. For both acute and chronic
      pain, a single agent may be less effective than combinations of analgesics with
      different mechanisms of action.

PMID- 15473675
TI  - Hemophilic arthropathy.
AB  - The most common clinical manifestation of hemophilia is arthropathy secondary to
      recurrent hemarthroses and chronic synovitis. Joint-surface erosions secondary to
      chronic synovitis often occur in early childhood and progress to advanced
      arthropathy by late adolescence. The knee, elbow, ankle, hip, and shoulder are
      the most commonly involved joints. Management of hemophilic arthropathy has
      advanced with the development of purified clotting factor concentrates and
      procedures to prevent chronic synovitis. Radiosynovectomy using beta particle
      emitting radiocolloids has been effective in dramatically reducing the frequency
      of hemarthroses and resolving chronic synovitis. The most common surgical
      procedures used to manage hemophilic arthropathy are synovectomy, joint
      debridement, fusion, and joint arthroplasty. Late infection and arthrofibrosis
      complicate joint arthroplasty more often in these patients than in patients with
      other forms of arthritis. The high incidence of late infection may relate to
      frequent intravenous self-infusion of clotting factor combined with immune
      suppression. Despite the medical and surgical complexities of hemophilic
      arthropathy, orthopaedic procedures have a high incidence of patient
      satisfaction.

PMID- 15473676
TI  - Lateral compression injuries in the pediatric elbow: Panner's disease and
      osteochondritis dissecans of the capitellum.
AB  - Lateral compression injuries of the elbow typically occur in throwing athletes
      and gymnasts. In the preadolescent and adolescent patient, these injuries
      predominantly include Panner's disease and osteochondritis dissecans. Panner's
      disease, an osteochondrosis of the capitellum, is a rare disorder that usually
      affects the dominant extremity in individuals younger than age 10 years.
      Symptomatic management of Panner's disease consisting of reduction of stressful
      activities of the elbow is usually sufficient to allow resolution. Although a
      prolonged period is required for healing, most patients demonstrate excellent
      long-term results. Osteochondritis dissecans of the capitellum typically occurs
      in adolescents and is associated with loose body formation. Panner's disease and
      osteochondritis dissecans likely represent a continuum of disordered endochondral
      ossification with presentation and prognosis dependent primarily on age at onset.

PMID- 15473677
TI  - Sacroiliac joint pain.
AB  - The sacroiliac joint is a source of pain in the lower back and buttocks in
      approximately 15% of the population. Diagnosing sacroiliac joint-mediated pain is
      difficult because the presenting complaints are similar to those of other causes
      of back pain. Patients with sacroiliac joint-mediated pain rarely report pain
      above L5; most localize their pain to the area around the posterior superior
      iliac spine. Radiographic and laboratory tests primarily help exclude other
      sources of low back pain. Magnetic resonance imaging, computed tomography, and
      bone scans of the sacroiliac joint cannot reliably determine whether the joint is
      the source of the pain. Controlled analgesic injections of the sacroiliac joint
      are the most important tool in the diagnosis. Treatment modalities include
      medications, physical therapy, bracing, manual therapy, injections,
      radiofrequency denervation, and arthrodesis; however, no published prospective
      data compare the efficacy of these modalities.

PMID- 15473678
TI  - Congenital scoliosis.
AB  - Congenital scoliosis is caused by early embryologic errors in vertebral column
      formation. Defining the deformity, predicting the natural history, and applying
      the correct treatment can help ensure successful management. Most congenital
      spine anomalies can be classified, and many have a predictable natural history.
      Because the deformities are associated with other organ system anomalies in more
      than half of patients, the surgeon should look for cardiac, auditory,
      genitourinary, and renal anomalies. Intraspinal abnormalities are present in
      approximately one third of patients with congenital spine deformities. Curve
      progression is best documented by measuring identical landmarks on sequential
      radiographs. Magnetic resonance imaging is warranted when curve progression is
      established or when surgical intervention is planned. Management of progressive
      deformity is generally by early in situ fusion because orthotic treatment is
      rarely appropriate. Other surgical techniques include combined anterior and
      posterior epiphysiodesis, hemivertebra resection, and reconstructive osteotomies.

PMID- 15473679
TI  - Clinical nerve conduction and needle electromyography studies.
AB  - The electrodiagnostic study, consisting of nerve conduction studies and needle
      electromyography, is a useful adjunct to the clinical examination of the
      peripheral nervous system. The three types of nerve conduction study are motor,
      sensory, and mixed, of which motor is the least sensitive. Electromyography
      records the intrinsic electrical activity of muscle fibers, thus providing the
      physiologic status of muscle function. To interpret the electrodiagnostic study
      results, the clinician must understand the anatomic and physiologic basis of the
      studies. Peripheral nerve entrapment initially results in focal demyelination;
      thus, nerve conduction velocity slows across the site. However, with
      radiculopathy and nerve root compression, the nerve conduction study may be
      normal. Both nerve trauma and polyneuropathy show marked differences in their
      effect on the results of electrodiagnostic studies.

PMID- 15473680
TI  - Proteomics and leukocytes: an approach to understanding potential molecular
      mechanisms of inflammatory responses.
AB  - Leukocytes play an important role in the progression of disease and leukocyte
      derived proteins are associated with the pathogenesis of the disease. Leukocyte
      activation causes production of inflammatory mediators, over-expression of cell
      surface adhesion molecules, and an increase in migration and infiltration,
      phagocytosis, and degranulation, as well as receptor phosphorylation and signal
      transduction. An increasing number of studies on the application of leukocyte
      proteomics have appeared in mapping protein profiles of inflammatory cells,
      contributing to the understanding of potential mechanisms involved in leukocyte
      function. Together with improvements in proteomic technology in leukocyte
      research, leukocyte proteomic analysis becomes more simple, rapid, flexible,
      sensitive, and specific. This enables proteomic investigation of activated or non
      activated leukocytes to be highly focused on defined suborgans or specific
      signaling pathways. Research in leukocyte proteomics is progressing from
      fingerprinting to functioning, human cell lines to primary leukocytes, non
      activated cells to inflammatory mediator-stimulated cells, in vitro culture to in
      vivo challenge, and animal models to human disease. A number of newly identified
      proteins from leukocyte proteomics may offer new mechanism-orientated targets for
      drug discovery and development.

PMID- 15473681
TI  - Genomic messaging system and DNA mark-up language for information-based
      personalized medicine with clinical and proteome research applications.
AB  - The convergence of clinical medicine and the Life Sciences, commencing with
      opportunities in clinical trials and clinically linked medical research, presents
      many novel challenges. The Genomic Messaging System (GMS) described here was
      originally developed as a tool for assembling clinical genomic records of
      individual and collective patients, and was then generalized to become a flexible
      workflow component that will link clinical records to a variety of computational
      biology research tools, for research and ultimately for a more personalized,
      focused, and preventative healthcare system. Prominent among the applications
      linked are protein science applications, including the rapid automated modeling
      of patient proteins with their individual structural polymorphisms. In an initial
      study, GMS formed the basis of a fully automated system for modeling patient
      proteins with structural polymorphisms as a basis for drug selection and
      ultimately design on an individual patient basis.

PMID- 15473682
TI  - Riboproteomics of the hepatitis C virus internal ribosomal entry site.
AB  - Hepatitis C virus (HCV) protein translation is mediated by a cis-acting RNA, an
      internal ribosomal entry site (IRES), located in the 5' nontranslated region of
      the viral RNA. To examine proteins bound to the IRES, which could include
      proteins important for its function as well as potential drug targets, we used
      shotgun peptide sequencing to identify proteins in quadruplicate protein affinity
      extracts of lysed Huh7 cells, obtained using a biotinylated IRES. Twenty-six
      proteins bound the HCV IRES but not a reversed complementary sequence RNA or
      vector RNA controls. These included five ribosomal subunits, nine eukaryotic
      initiation factor 3 subunits, and novel interacting proteins such as the
      cytoskeletal-related proteins actin, FHOS (formin homologue overexpressed in
      spleen) and MIP-T3 (microtubule interacting protein that associates with TRAF3).
      Other novel HCV IRES-binding proteins included UNR (upstream of N-ras), UNR
      interacting protein, and the RNA-binding proteins PAI-1 (plasminogen activator
      inhibitor-1) mRNA binding protein and Ewing sarcoma breakpoint 1 region protein
      EWS. A large set of additional proteins bound both the HCV IRES and a reversed
      complementary IRES sequence control, including the known HCV interactors PTB
      (polypyrimidine tract binding protein), the La autoantigen, and nucleolin. The
      discovery of these novel HCV IRES-binding proteins suggests links between IRES
      biology and the cytoskeleton, signal transduction, and other cellular functions.

PMID- 15473683
TI  - Open mass spectrometry search algorithm.
AB  - Large numbers of MS/MS peptide spectra generated in proteomics experiments
      require efficient, sensitive and specific algorithms for peptide identification.
      In the Open Mass Spectrometry Search Algorithm (OMSSA), specificity is calculated
      by a classic probability score using an explicit model for matching experimental
      spectra to sequences. At default thresholds, OMSSA matches more spectra from a
      standard protein cocktail than a comparable algorithm. OMSSA is designed to be
      faster than published algorithms in searching large MS/MS datasets.

PMID- 15473684
TI  - Characterization of the 70S Ribosome from Rhodopseudomonas palustris using an
      integrated "top-down" and "bottom-up" mass spectrometric approach.
AB  - We present a comprehensive mass spectrometric approach that integrates intact
      protein molecular mass measurement ("top-down") and proteolytic fragment
      identification ("bottom-up") to characterize the 70S ribosome from
      Rhodopseudomonas palustris. Forty-two intact protein identifications were
      obtained by the top-down approach and 53 out of the 54 orthologs to Escherichia
      coli ribosomal proteins were identified from bottom-up analysis. This integrated
      approach simplified the assignment of post-translational modifications by
      increasing the confidence of identifications, distinguishing between isoforms,
      and identifying the amino acid positions at which particular post-translational
      modifications occurred. Our combined mass spectrometry data also allowed us to
      check and validate the gene annotations for three ribosomal proteins predicted to
      possess extended C-termini. In particular, we identified a highly repetitive C
      terminal "alanine tail" on L25. This type of low complexity sequence, common to
      eukaryotic proteins, has previously not been reported in prokaryotic proteins. To
      our knowledge, this is the most comprehensive protein complex analysis to date
      that integrates two MS techniques.

PMID- 15473685
TI  - The statistical significance of protein identification results as a function of
      the number of protein sequences searched.
AB  - The potential for obtaining a true mass spectrometric protein identification
      result depends on the choice of algorithm as well as on experimental factors that
      influence the information content in the mass spectrometric data. Current methods
      can never prove definitively that a result is true, but an appropriate choice of
      algorithm can provide a measure of the statistical risk that a result is false,
      i.e., the statistical significance. We recently demonstrated an algorithm,
      Probity, which assigns the statistical significance to each result. For any
      choice of algorithm, the difficulty of obtaining statistically significant
      results depends on the number of protein sequences in the sequence collection
      searched. By simulations of random protein identifications and using the Probity
      algorithm, we here demonstrate explicitly how the statistical significance
      depends on the number of sequences searched. We also provide an example on how
      the practitioner's choice of taxonomic constraints influences the statistical
      significance.

PMID- 15473686
TI  - Rapid and sensitive amino-acid sequencing of cloning Thermus thermophilus HB8
      ferredoxin by proteomics.
AB  - Recombinant holo Thermus thermophilus [7Fe-8S] ferredoxin was synthesized by
      cloning from Thermus thermophilus HB8 gene. A specific sequence (Pro-His-Val-Ile)
      at the N-terminus of the recombinant ferredoxin was determined by a rapid and
      highly sensitive mass spectral method using a novel Ru(II) Edman reagent,
      [(tpy)Ru(tpy-C6H4-NCS)](PF6)2 (tpy=terpyridine). The formation of the recombinant
      holoTtFd was established by the characteristic absorptions and CD extrema as [7Fe
      8S] ferredoxin. The catalytic electron-transfer reactivity of the [7Fe-8S]
      ferredoxin between ferredoxin-NADP+ reductase and cytochrome c was recognized.

PMID- 15473687
TI  - Integrated protein microchip assay with dual fluorescent- and MALDI read-out.
AB  - A pore chip protein array (PCPA) concept based on a dual readout configuration,
      fluorescence imaging, and MALDI-TOF MS has been developed. Highly packed, (>4000
      spots/cm2), antibody arrays were dispensed on the porous chip by using a piezo
      electric microdispenser. Sandwich assay was made after blocking by addition of a
      secondary antibody either IgG-FITC-labeled or anti-Ang II. The antigen in the
      first system was a large protein (IgG), and in the other system, a FITC marked
      peptide Angiotensin II (Ang II) was used. Ang II antibodies showed specificity
      for Ang II, while the Ang I antibodies showed binding properties for Ang I, II,
      and Renin. Fluorescence and MALDI TOF MS read-out was made for IgG and Ang II. A
      major advantage of the dual read-out PCPA approach is that both affinity binding
      and mass identity are derived. Detection limits for Ang II on the chip is as low
      as 500 zmol (Ang II).

PMID- 15473688
TI  - Proteome analysis of rhoptry-enriched fractions isolated from Plasmodium
      merozoites.
AB  - The rhoptries of Plasmodium species participate in merozoite invasion and
      modification of the host erythrocyte. However, only a few rhoptry proteins have
      been identified using conventional gene identification protocols. To investigate
      the protein organization of this organelle and to identify new rhoptry proteins,
      merozoite rhoptries from three different Plasmodium rodent species were enriched
      by sucrose density gradient fractionation, and subjected to proteome analysis
      using multidimensional protein identification technology (MudPIT); 148 proteins
      were identified. To distinguish abundant cellular contaminants from bona fide
      organellar proteins, a differential analysis comparing the proteins in the
      rhoptry-enriched fractions to proteins identified from whole cell lysates of P.
      berghei mixed asexual blood stages was undertaken. In addition, the proteins
      detected were analyzed for the presence of transmembrane domains, secretory
      signal peptide, cell adhesion motifs, and/or rhoptry-specific tyrosine-sorting
      motifs. Combining the differential analysis and bioinformatic approaches, a set
      of 36 proteins was defined as being potentially located to the Plasmodium
      rhoptries. Among these potential rhoptry proteins were homologues of known
      rhoptry proteins, proteases, and enzymes involved in lipid metabolism. Molecular
      characterization and understanding of the supramolecular organization of these
      novel potential rhoptry proteins may assist in the identification of new
      intervention targets for the asexual blood stages of malaria.

PMID- 15473689
TI  - DBParser: web-based software for shotgun proteomic data analyses.
AB  - We describe a web-based program called 'DBParser' for rapidly culling, merging,
      and comparing sequence search engine results from multiple LC-MS/MS peptide
      analyses. DBParser employs the principle of parsimony to consolidate redundant
      protein assignments and derive the most concise set of proteins consistent with
      all of the assigned peptide sequences observed in an experiment or series of
      experiments. The resulting reports summarize peptide and protein identifications
      from multidimensional experiments that may contain a single data set or combine
      data from a group of data sets, all related to a single analytical sample.
      Additionally, the results of multiple experiments, each of which may contain
      several data sets, can be compared in reports that identify features that are
      common or different. DBParser actively links to the primary mass spectral data
      and to public online databases such as NCBI, GO, and Swiss-Prot in order to
      structure contextually specific reports for biologists and biochemists.

PMID- 15473690
TI  - Proteome analysis of gastric cancer metastasis by two-dimensional gel
      electrophoresis and matrix assisted laser desorption/ionization-mass spectrometry
      for identification of metastasis-related proteins.
AB  - A well-described animal model was used to understand the molecular mechanisms of
      carcinogenesis and metastasis of gastric cancer at the protein level. Gastric
      cancer was induced in 12 Wistar rats by oral administration of N-methyl-N'-Nitro
      N-Nitrosoguanidine (MNNG). The protein expression patterns of normal gastric
      tissue, gastric cancer, and corresponding metastases were analyzed by proteomics
      in matched tissues of 3 rats. Proteins in the region of molecular masses of 15-75
      kDa and an isoelectric point of 3-7 were separated by two-dimensional
      electrophoresis (2-DE) and identified by peptide fingerprinting with matrix
      assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF
      MS). Twenty-seven spots corresponding to 25 different proteins served as
      landmarks for comparison between tissues. The identified proteins included
      cytoskeletal proteins, stress associated proteins, proteins involved in signal
      transduction, cell proliferation and differentiation, and metabolism. Eleven
      proteins were up-regulated and 2 proteins were down-regulated in tumor tissue
      when compared with normal tissue. Twelve proteins were up-regulated and 8
      proteins were down-regulated in the metastases when compared with the primary
      tumor. The overexpression of HSP27 in gastric cancer was confirmed by
      immunohistochemical analysis of human gastric cancer specimens. Combining well
      defined animal models with proteome analysis will improve our understanding of
      the fundamental changes that contribute to the process of carcinogenesis and the
      formation of metastases in gastric cancer.

PMID- 15473691
TI  - Two-dimensional liquid chromatography study of the human whole saliva proteome.
AB  - The human whole saliva proteome was investigated using two-dimensional liquid
      chromatography (2-DLC). The 2-DLC study was able to identify, with high
      confidence, 102 proteins including most known salivary proteins (35), and a large
      number of common serum proteins (67). Peptides from proline-rich proteins,
      abundant in saliva, had unusual cleavage sites and were frequently only partially
      tryptic. Three proteins not previously observed in human saliva were also
      detected. Significantly greater numbers of identified proteins, including high
      molecular weight, low molecular weight, and proline-rich proteins, were found
      with 2-DLC compared to previously reported two-dimensional gel electrophoresis
      studies.

PMID- 15473692
TI  - High-throughput, fluorescence-based screening for soluble protein expression.
AB  - Protein expression screening methods are essential for proteomic scale
      characterization of gene and cDNA expression libraries. Screening methods are
      also important for the identification of highly expressed protein targets, for
      example, in quantities suitable for high-throughput screening and protein
      structural studies. To address these needs, we describe the implementation of
      several rapid, fluorescence-based protein expression screening strategies using
      Escherichia coli or E. coli-based in vitro transcription/translation (IVT)
      systems. In vitro expression screening is fast, convenient and, as we show,
      correlates well with in vivo expression. For screening, expressed proteins are
      labeled either as fusions with green fluorescent protein (GFP) or through
      translational incorporation of a fluorescent amino acid derivative, BODIPY-FL
      Lysine. Fluorescence-based detection of GFP fusions or BODIPY-labeled proteins is
      considerably faster than other common expression screening methods, such as
      immunological detection of gels or dot blots. Furthermore, in vitro and in vivo
      screening used together yield a larger set of expressed proteins than either
      method alone. Specifically labeled proteins in cellular lysates are detected in
      one of three formats: a microplate using a fluorescence plate reader, a dot-blot
      using a fluorescence scanner or a microarray using a laser scanner. We have
      established a correlation among the various detection formats, which validates
      the use of protein microarrays for expression screening. Production of expressed
      proteins detected through screening can be scaled up either using IVT reactions
      or with in vivo expression systems in the absence of a fluorophore for subsequent
      characterization of protein function or interactions.

PMID- 15473693
TI  - Effects of single amino acid substitution on the collision-induced dissociation
      of intact protein ions: Turkey ovomucoid third domain.
AB  - Expanded understanding of the factors that direct polypeptide ion fragmentation
      can lead to improved specificity in the use of tandem mass spectrometry for the
      identification and characterization of proteins. Like the fragmentation of
      peptide cations, the dissociation of whole protein cations shows several
      preferred cleavages, the likelihood for which is parent ion charge dependent.
      While such cleavages are often observed, they are far from universally observed,
      despite the presence of the residues known to promote them. Furthermore,
      cleavages at residues not noted to be common in a variety of proteins can be
      dominant for a particular protein or protein ion charge state. Motivated by the
      ability to study a small protein, turkey ovomucoid third domain, for which a
      variety of single amino acid variants are available, the effects of changing the
      identity of one amino acid in the protein sequence on its dissociation behavior
      were examined. In particular, changes in amino acids associated with C-terminal
      aspartic acid cleavage and N-terminal proline cleavage were emphasized.
      Consistent with previous studies, the product ion spectra were found to be
      dependent upon the parent ion charge state. Furthermore, the fraction of possible
      C-terminal aspartic acid cleavages observed to occur for this protein was
      significantly larger than the fraction of possible N-terminal proline cleavages.
      In fact, very little N-terminal proline cleavage was noted for the wild-type
      protein despite the presence of three proline residues in the protein. The
      addition/removal of proline and aspartic acids was studied along with changes in
      selected residues adjacent to proline residues. Evidence for inhibition of
      proline cleavage by the presence of nearby basic residues was noted, particularly
      if the basic residue was likely to be protonated.

PMID- 15473694
TI  - Comprehensive proteomic analysis of human pancreatic juice.
AB  - Proteomic technologies provide an excellent means for analysis of body fluids for
      cataloging protein constituents and identifying biomarkers for early detection of
      cancers. The biomarkers currently available for pancreatic cancer, such as CA19
      9, lack adequate sensitivity and specificity contributing to late diagnosis of
      this deadly disease. In this study, we carried out a comprehensive
      characterization of the "pancreatic juice proteome" in patients with pancreatic
      adenocarcinoma. Pancreatic juice was first fractionated by 1-dimensional gel
      electrophoresis and subsequently analyzed by liquid chromatography tandem mass
      spectrometry (LC-MS/MS). A total of 170 unique proteins were identified including
      known pancreatic cancer tumor markers (e.g., CEA, MUC1) and proteins
      overexpressed in pancreatic cancers (e.g., hepatocarcinoma-intestine
      pancreas/pancreatitis-associated protein (HIP/PAP) and lipocalin 2). In addition,
      we identified a number of proteins that have not been previously described in
      pancreatic juice (e.g., tumor rejection antigen (pg96) and azurocidin).
      Interestingly, a novel protein that is 85% identical to HIP/PAP was identified,
      which we have designated as PAP-2. The proteins identified in this study could be
      directly assessed for their potential as biomarkers for pancreatic cancer by
      quantitative proteomics methods or immunoassays.

PMID- 15473695
TI  - Antigens up the nose: identification of putative biomarkers for nasal tolerance
      induction functional studies combined with proteomics.
AB  - Intranasal autoantigen delivery is the most effective means of inducing mucosal
      tolerance and suppression of autoimmune disease. In an effort to identify markers
      of the "tolerant state", we employed proteomics technology at the level of the
      cervical lymph node. The analysis revealed that nasal antigen administration
      (without adiuvant) led to modulation of various proteins among which the most
      prominent were haptoglobin, nonintegrin 67 kDa laminin receptor, and MRP8. The
      immunoregulatory haptoglobin may qualify as (bio)marker for effective
      immunotherapy.

PMID- 15473696
TI  - Evaluation of metabolic labeling for comparative proteomics in breast cancer
      cells.
AB  - Protein expression patterns in the cytosol of MCF-7 cells resistant to adriamycin
      and to adriamycin/verapamil were compared to that of the parental MCF-7 cell line
      and to each other using metabolic labeling and two-dimensional gel
      electrophoresis. Growing the parental MCF-7 cell line in 13C6-arginine- and 13C6
      lysine-enriched medium resulted in C-terminal labeling of all tryptic peptides.
      The culture media was optimized for the incorporation of these labeled amino
      acids under conditions that also supported cell growth. Protein abundances were
      found to be distinctive in MCF-7 cells resistant to adriamycin and those selected
      for resistance to both adriamycin and verapamil.

PMID- 15473697
TI  - Insights from modeling the tertiary structure of human BACE2.
AB  - BACE1, or beta-secretase, is a putative prime therapeutic target for the
      treatment of Alzheimer's disease. Mapping to the Down syndrome critical region
      (chromosome 21) and identified as a homologue of BACE1, BACE2 also cleaves
      amyloid precursor protein at the beta-site. Thus, BACE2, named also as Asp1 or
      Memapsin1, represents a second beta-secretase candidate. In this paper, the
      tertiary structure of the protease domain of BACE2 was developed. Although the
      overall structural topology between BACE1 and BACE2 protease domains is quite
      similar, the former contains 3 disulfide bonds but the latter only two.
      Particularly, a subtle structural difference around the DTG/DSG active site
      between the two structures has been observed that is useful for the in-depth
      selectivity study of BACE1 and BACE2 inhibitors, stimulating new therapeutic
      strategies for the treatment of Alzheimer's disease and Down syndrome as well.

PMID- 15473698
TI  - Characterization of low abundant membrane proteins using the protein sequence tag
      technology.
AB  - About 25% of open reading frames in fully sequenced genomes are estimated to
      encode transmembrane proteins that represent valuable targets for drugs. However,
      the global analysis of membrane proteins has been proven to be problematic, e.g.,
      because of their very amphiphilic nature. In this paper, we show that the
      recently published Protein Sequence Tag (PST) technology combined with an
      efficient sample preparation is a powerful method to perform protein analysis of
      highly enriched membrane fractions. The PST approach is a gel-free proteomics
      tool for the analysis of proteins, which relies on a "sampling" strategy by
      isolating N-terminal protein sequence tags from cyanogen bromide cleaved
      proteins. The identification of these N-terminal PST peptides is based on LC
      MS/MS. The effectiveness of the technology is demonstrated for a membrane
      fraction, which was isolated from crude mitochondria of yeast after alkaline
      sodium carbonate treatment. The PST approach performed on this fraction analyzed
      148 proteins, whereas 84% are identified as membrane proteins. More
      interestingly, among these membrane proteins 56% are predicted to be of low
      abundance. These encouraging results are an important step toward the development
      of a quantitative PST approach (qPST) for the differential display of membrane
      protein analysis.

PMID- 15473700
TI  - Suffocation of nerve fibers by living nanovesicles: a model simulation--part II.
AB  - Nanobacteria may cause peripheral neuropathy by adhesion to the perineurium. This
      hypothesis receives support from five independent observations: (1)
      identification of perineurial apatite in diabetic patients with peripheral
      neuropathy, (2) massive presence of nanobacteria in a diabetic patient, (3)
      beneficial effect of lasers on peripheral neuropathy, (4) model simulation
      indicating that perineurial deposition and attachment of nanobacteria is
      encouraged by both their size and chemical nature, and (5) transient inhibition
      of neural function by apatite. Initial deposition of (stressed) nanobacteria is
      promoted by a slime thought to consist of proteins, calcium, and phosphate, and
      is most likely followed by an immobilization phase, mediated by a bioadhesive
      capacity of the apatite. Proteomics may hold the key to control both attachment
      processes.

PMID- 15473699
TI  - Potential for false positive identifications from large databases through tandem
      mass spectrometry.
AB  - The biomedical research community at large is increasingly employing shotgun
      proteomics for large-scale identification of proteins from enzymatic digests.
      Typically, the approach used to identify proteins and peptides from tandem mass
      spectral data is based on the matching of experimentally generated tandem mass
      spectra to the theoretical best match from a protein database. Here, we present
      the potential difficulties of using such an approach without statistical
      consideration of the false positive rate, especially when large databases, as are
      encountered in eukaryotes are considered. This is illustrated by searching a
      dataset generated from a multidimensional separation of a eukaryotic tryptic
      digest against an in silico generated random protein database, which generated a
      significant number of positive matches, even when previously suggested score
      filtering criteria are used.

PMID- 15473701
TI  - Three-dimensional model of the pore form of anthrax protective antigen. Structure
      and biological implications.
AB  - Although pore formation by protective antigen (PA) is critical to cell
      intoxication by anthrax toxin (AT), the structure of the pore form of PA (the
      PA63 pore) has not been determined. Hence, in this study, the PA63 pore was
      modeled using the X-ray structures of monomeric PA and heptameric alpha-hemolysin
      (alpha-HL) as templates. The PA63 pore model consists of two weakly associated
      domains, namely the cap and stem domains. The ring-like cap domain has a length
      of 80 A and an outside diameter of 120 A, while the cylinder-like stem domain has
      a length of 100 A and outside diameter of approximately 28 A. This provides the
      PA63 pore model with a length of 180 A. Based on experimental results, the
      channel in the PA63 pore model was built to have a minimum diameter of ~12 A,
      depending on side chain conformations. Because of its large size and structural
      complexity, the all-atom model of the PA63 pore is the end-stage construction of
      four separate modeling projects described herein. The final model is consistent
      with published experimental results, including mutational analysis and channel
      conductance experiments. In addition, the model was energetically and
      hydropathically refined to optimize molecular packing within the protomers and at
      the protomer-protomer interfaces. By providing atomic detail to biochemical and
      biophysical data, the PA63 pore model may afford new insights into the binding
      mode of PA on the membrane surface, the prepore-pore transition, and the
      mechanism of cell entry by anthrax toxin.

PMID- 15473702
TI  - Collective motions of RNA polymerases. Analysis of core enzyme, elongation
      complex and holoenzyme.
AB  - The anisotropic network model (ANM), a coarse-grained normal mode analysis, is
      used to study the vibrational dynamics of RNA polymerases (RNAP) around the
      native states. The theoretical temperature factors obtained from ANM are in
      conformity with the experimental values for yeast and bacterial RNAP structures
      in free and complex forms. In the low-frequency collective modes that are related
      to biological function, both bacterial and yeast RNAPs with a crab claw shape
      display an opening/closing of the cleft due to the rigid-body motion of the clamp
      (bottom pincer), which has been also predicted by experiments, together with the
      motion of the top pincer. Even though slightly lower fluctuations are observed in
      the elongation complex of yeast RNAP, similar clamp motion still exists in
      collective modes, which should be concerted with the flexible switches and the
      bridge helix in driving the transcription process, pointing at the possibility of
      a ratchet-like mechanism. Two different bacterial holoenzyme (HE) structures are
      studied, which may have functional significance at different stages of
      transcription initiation. In a specific closed conformation of the HE, the clamp
      and top pincer are highly immobilized due to interactions with the sigma subunit.
      In contrast, the deformation of the top pincer is not inhibited in a relatively
      open conformation of another HE, which may help load the DNA into the cleft
      during transcription initiation, even though the clamp motion is still inhibited.

PMID- 15473703
TI  - Engineering strontium binding affinity in an EF-hand motif: a quantum chemical
      and molecular dynamics study.
AB  - Proteins with the ability to specifically bind strontium would potentially be of
      great use in the field of nuclear waste management. Unfortunately, no such
      peptides or proteins are known -- indeed, it is uncertain whether they exist
      under natural conditions due to low environmental concentrations of strontium. To
      investigate the possibility of devising such molecules, one of us (CV), in a
      previous experimental study, proposed starting from an EF-hand motif of the
      protein calmodulin and mutating some residues to change the motif's specificity
      for calcium into one for strontium. In this paper, which represents a theoretical
      complement to the experimental work, we analyzed small-molecule crystallographic
      structures and performed quantum chemical calculations to identify possible
      mutations. We then constructed seven mutant sequences of the EF-hand motif and
      analyzed their dynamical and binding behaviors using molecular dynamics
      simulations and free-energy calculations (using the MM/PBSA method). As a result
      of these analyzes we were able to isolate some characteristics that could lead to
      mutant peptides with enhanced strontium affinity.

PMID- 15473704
TI  - Disialogangliosides and their interaction with cholera toxin - investigation by
      molecular modeling, molecular mechanics and molecular dynamics.
AB  - Molecular mechanics and molecular dynamics studies are performed to investigate
      the conformational preference of cell surface disialogangliosides (GD1A, GD1B and
      GD3) in aqueous environment. The molecular mechanics calculation reveals that
      water mediated hydrogen bonding network plays a significant role in the
      structural stabilization of GD1A, GD1B and GD3. These water mediated hydrogen
      bonds not only exist between neighboring residues but also exist between residues
      that are separated by 2 to 3 residues in between. The conformational energy
      difference between different conformational states of gangliosides correlates
      very well with the number of water mediated and direct hydrogen bonds. The
      spatial flexibility of NeuNAc of gangliosides at the binding site of cholera
      toxin is worked out. The NeuNAc has a limited allowed eulerian space at the
      binding site of Cholera Toxin (2.4%). The molecular modeling, molecular mechanics
      and molecular dynamics of disialoganglioside-cholera toxin complex reveal that
      cholera toxin can accommodate the disialoganglioside GD1A in three different
      modes. A single mode of binding is permissible for GD1B and GD3. Direct and water
      mediated hydrogen bonding interactions stabilizes these binding modes and play an
      essential role in defining the order of specificity for different
      disialogangliosides towards cholera toxin. This study not only provides models
      for the disialoganglioside-cholera toxin complexes but also identifies the NeuNAc
      binding site as a site for design of inhibitors that can restrict the pathogenic
      activity of cholera toxin.

PMID- 15473705
TI  - Genomic choice of codons in 16 microbial species.
AB  - We study the codon usage over whole set of ORFs of 16 unicellular microbial
      species: eight archaebacteria, seven eubacteria, and one eukarya. We first try to
      define, for each species, the neutral expected codon usage to better approach
      subsequently the influence of selection. Overlapping triplets counted from the
      complete DNA genomic sequence and mean amino acid composition of ORFs allow us to
      build satisfying expected codon usage for each species. Within species deviation
      from this neutral model is then studied through Correspondence Analysis and
      characterization with bias index, N(C)' (effective number of codons reported to
      neutral model). Our results are compared to previously published ones for three
      species and let appear good agreement in spite of very different methods. We thus
      propose set of codons probably preferred by selection for nine other species. In
      the four last species, no clear preference can be evidenced. Finally, we
      characterize variation of codon usage over functional categories. We propose that
      the high degree of bias of proteins involved in translation, ribosomal structure
      and biogenesis has a positive influence on overexpression of the corresponding
      genes under optimum growth conditions and is a negative regulator of the same
      genes when amino acids become limited resources.

PMID- 15473706
TI  - Ice-water interface migration by temperature controlling for stretching of DNA
      molecules.
AB  - This report shows a new DNA stretching method using migration of an ice-water
      interface. DNA molecules were stretched accompanying the migration of the solid
      liquid interface and immobilized in frozen area. This simple method needs no
      chemical modification to keep DNA in the stretched form. For full stretching of
      DNA molecules, one terminus of the DNA molecules were anchored on silanized
      substrate. The anchored DNA molecules were stretched by freezing the DNA
      solution. The stretched DNA molecules were observed after sublimation of the
      frozen solution keeping its stretched form on silanized surface which had no
      attractive interaction with DNA molecules except for the SH-modified terminus in
      solution. An infrared (IR) laser beam was introduced to a frozen DNA solution
      through an objective lens for local area melting of the solution. Scanning of the
      laser irradiation caused stretching and enclosing of DNA molecules in the frozen
      area followed by migration of the solid-liquid interface.

PMID- 15473707
TI  - Homology modeling of the CG-specific DNA methyltransferase SssI and its complexes
      with DNA and AdoHcy.
AB  - Prokaryotic DNA methyltransferase M.SssI recognizes and methylates C5 position of
      the cytosine residue within the CG dinucleotides in DNA. It is an excellent model
      for studying the mechanism of interaction between CG-specific eukaryotic
      methyltransferases and DNA. We have built a structural model of M.SssI in complex
      with the substrate DNA and its analogues as well as the cofactor analogue S
      adenosyl-L-homocysteine (AdoHcy) using the previously solved structures of M.HhaI
      and M.HaeIII as templates. The model was constructed according to the recently
      developed "FRankenstein's monster" approach. Based on the model, amino acid
      residues taking part in cofactor binding, target recognition and catalysis were
      predicted. We also modeled covalent modification of the DNA substrate and studied
      its influence on protein-DNA interactions.

PMID- 15473708
TI  - New elements of the termination of transcription in prokaryotes.
AB  - We report here that phased runs of adenines and thymines are very frequent in the
      neighborhood of 3' of the coding regions of Escherichia coli and Bacillus
      subtilis. These findings suggest that the DNA curvature could affect
      transcription termination either directly, through contacts with RNA polymerase,
      or indirectly, via contacts with some regulatory proteins.

PMID- 15473709
TI  - Efficient search on energy minima for structure prediction of nucleic acid
      motifs.
AB  - Structure prediction of non-canonical motifs such as mismatches, extra unmatched
      nucleotides or internal and hairpin loop structures in nucleic acids is of great
      importance for understanding the function and design of nucleic acid structures.
      Systematic conformational analysis of such motifs typically involves the
      generation of many possible combinations of backbone dihedral torsion angles for
      a given motif and subsequent energy minimization (EM) and evaluation. Such
      approach is limited due to the number of dihedral angle combinations that grows
      very rapidly with the size of the motif. Two conformational search approaches
      have been developed that allow both an effective crossing of barriers during
      conformational searches and the computational demand grows much less with system
      size then search methods that explore all combinations of backbone dihedral
      torsion angles. In the first search protocol single torsion angles are flipped
      into favorable states using constraint EM and subsequent relaxation without
      constraints. The approach is repeated in an iterative manner along the backbone
      of the structural motif until no further energy improvement is obtained. In case
      of two test systems, a DNA-trinucleotide loop (sequence: GCA) and a RNA tetraloop
      (sequence: UUCG), the approach successfully identified low energy states close to
      experiment for two out of five start structures. In the second method randomly
      selected combinations of up to six backbone torsion angles are simultaneously
      flipped into preset ranges by a short constraint EM followed by unconstraint EM
      and acceptance according to a Metropolis acceptance criterion. This combined
      stochastic/EM search was even more effective than the single torsion flip
      approach and selected low energy states for the two test cases in between two and
      four cases out of five start structures.

PMID- 15473710
TI  - Tetraplex structure formation in the thrombin-binding DNA aptamer by metal
      cations measured by vibrational spectroscopy.
AB  - Formation of intramolecular tetraplex structures by the thrombin-binding DNA
      aptamer (TBA) in the presence of K(+), Pb(2+), Ba(2+), Sr(2+) and Mn(2+) has been
      studied by vibrational spectroscopy. All tetraplex structures contain G-G
      Hoogsteen type base pairing, both C2'endo/anti and C2'endo/syn deoxyguanosine
      glycosidic conformations and local B like form DNA phosphate geometries. Addition
      of Pb(2+) ions modifies the structure by interacting at the level of the guanine
      carbonyl groups. The very important downshift of the guanine C6=O6 carbonyl
      vibration mode in the TBA spectrum induced by the addition of one Pb(2+) ion per
      TBA molecule is in agreement with a localization of the metal ion between both
      guanine quartets. FTIR melting experiments show an important stabilization of the
      tetraplex structure upon addition of Pb(2+) ions (DeltaT = 15 degrees C). This
      strong interaction of lead cations may be correlated with a change in the
      geometry of the cage formed by the two guanine quartets. A similar but weaker
      effect is observed for barium and strontium cations.

PMID- 15473711
TI  - Differential scanning calorimetric study of the binding of the water of hydration
      to deoxyadenosine.
AB  - Differential scanning calorimetry was used to study the water of hydration in
      powder samples of deoxyadenosine (dA), a naturally occurring nucleoside. Though
      water of crystallization is present in samples which have not undergone heat
      treatment previously, dA was found to rehydrate at room temperature only at
      relative humidities (RHs) of 88% and higher. Rehydrated samples exhibited a
      single endothermic peak. At 95% RH, its activation energy was 1.61 +/- 0.06 eV
      and had an enthalpy change of 190 +/- 30 J/g. Experiments between 88 and 95% RH
      revealed that the energies are independent of RH, to within experimental error.
      This range of humidity corresponds to secondary hydration in DNA.

PMID- 15473712
TI  - Rovibrational product state distribution for inelastic H+D2 collisions.
AB  - Experimental measurements of rovibrational product state distributions for the
      inelastic scattering process H + D2(nu=0,j)-->H + D2(nu' = 1,2,j') are presented
      and compared with the results of quasiclassical and quantum mechanical
      calculations. Agreement between theory and experiment is almost quantitative. Two
      subtle trends are found: the relative amount of energy in product rotational
      excitation decreases slightly with increasing collision energy and increases
      slightly with increasing product vibrational excitation. These trends are the
      reverse of what has been found for reactive scattering in which the opposite
      trends are much more pronounced.

PMID- 15473713
TI  - A closed-shell coupled-cluster treatment of the Breit-Pauli first-order
      relativistic energy correction.
AB  - First-order relativistic corrections to the energy of closed-shell molecular
      systems are calculated, using all terms in the two-component Breit-Pauli
      Hamiltonian. In particular, we present the first implementation of the two
      electron Breit orbit-orbit integrals, thus completing the first-order
      relativistic corrections within the two-component Pauli approximation.
      Calculations of these corrections are presented for a series of small and light
      molecules, at the Hartree-Fock and coupled-cluster levels of theory. Comparisons
      with four-component Dirac-Coulomb-Breit calculations demonstrate that the full
      Breit-Pauli energy corrections represent an accurate approximation to a fully
      relativistic treatment of such systems. The Breit interaction is dominated by the
      spin-spin interaction, the orbit-orbit interaction contributing only about 10% to
      the total two-electron relativistic correction in molecules consisting of light
      atoms. However, the relative importance of the orbit-orbit interaction increases
      with increasing nuclear charge, contributing more than 20% in H(2)S.

PMID- 15473714
TI  - A semiclassical study of wave packet dynamics in anharmonic potentials.
AB  - Classical and semiclassical methods are developed to calculate and invert the
      wave packet motion measured in pump-probe experiments. With classical propagation
      of the Wigner distribution of the initial wave packet created by the pump pulse,
      we predict the approximate probe signal with slightly displaced recurrence peaks,
      and derive a set of first-order canonical perturbation expressions to relate the
      temporal features of the signal to the characteristics of the potential surface.
      A reduced dynamics scheme based on the Gaussian assumption leads to the correct
      center of mass motion but does not describe the evolution of the shape of the
      wave packet accurately. To incorporate the quantum interference into classical
      trajectories, we propose a final-value representation semiclassical method,
      specifically designed for the purpose of computing pump-probe signals, and
      demonstrate its efficiency and accuracy with a Morse oscillator and two
      kinetically coupled Morse oscillators. For the case of one-color pump probe, a
      simple phase-space quantization scheme is devised to reproduce the temporal
      profile at the left-turning point without actual wave packet propagation,
      revealing a quantum mechanical perspective of the nearly classical pump-probe
      signal.

PMID- 15473715
TI  - Linear scaling computation of the Fock matrix. VII. Parallel computation of the
      Coulomb matrix.
AB  - We present parallelization of a quantum-chemical tree-code for linear scaling
      computation of the Coulomb matrix. Equal time partition is used to load balance
      computation of the Coulomb matrix. Equal time partition is a measurement based
      algorithm for domain decomposition that exploits small variation of the density
      between self-consistent-field cycles to achieve load balance. Efficiency of the
      equal time partition is illustrated by several tests involving both finite and
      periodic systems. It is found that equal time partition is able to deliver 91%
      98% efficiency with 128 processors in the most time consuming part of the Coulomb
      matrix calculation. The current parallel quantum chemical tree code is able to
      deliver 63%-81% overall efficiency on 128 processors with fine grained
      parallelism (less than two heavy atoms per processor).

PMID- 15473716
TI  - Single molecule conductivity: the role of junction-orbital degeneracy in the
      artificially high currents predicted by ab initio approaches.
AB  - A priori evaluations, using Hartree-Fock self-consistent-field (SCF) theory or
      density-functional theory (DFT), of the current passing between two electrodes
      through a single bridging molecule result in predicted conductivities that may be
      up to one to two orders of magnitude larger than observed ones. We demonstrate
      that this is, in part, often due to the improper application of the computational
      methods. Conductivity is shown to arise from tunneling between junction states of
      the electrodes through the molecule; these states are inherently either quasi two
      fold or four-fold degenerate and always comprise the (highest occupied molecular
      orbital) HOMO band at the Fermi energy of the system. Frequently, in previous
      cluster based molecular conduction calculations, closed-shell SCF or Kohn-Sham
      DFT methods have been applied to systems that we demonstrate to be intrinsically
      open shell in nature. Such calculations are shown to induce artificial HOMO-LUMO
      (LUMO-lowest unoccupied molecular orbital) band splittings that Landauer-based
      formalisms for steady-state conduction interpret as arising from extremely rapid
      through-molecule tunneling at the Fermi energy, hence, overestimating the low
      voltage conductivity. It is demonstrated that these shortcomings can be
      eliminated, dramatically reducing calculated current magnitudes, through the
      alternate use of electronic-structure calculations based on the spin-restricted
      open-shell formalism and related multiconfigurational SCF of DFT approaches.
      Further, we demonstrate that most anomalies arising in DFT implementations arise
      through the use of hybrid density functionals such as B3LYP. While the enhanced
      band-gap properties of these functionals have made them the defacto standard in
      molecular conductivity calculations, we demonstrate that it also makes them
      particularly susceptible to open-shell anomalies.

PMID- 15473717
TI  - Extrapolating bound state data of anions into the metastable domain.
AB  - Computing energies of electronically metastable resonance states is still a great
      challenge. Both scattering techniques and quantum chemistry based L2 methods are
      very time consuming. Here we investigate two more economical extrapolation
      methods. Extrapolating bound states energies into the metastable region using
      increased nuclear charges has been suggested almost 20 years ago. We critically
      evaluate this attractive technique employing our complex absorbing
      potential/Green's function method that allows us to follow a bound state into the
      continuum. Using the (2)Pi(g) resonance of N2- and the (2)Pi(u) resonance of CO2-
      as examples, we found that the extrapolation works suprisingly well. The second
      extrapolation method involves increasing of bond lengths until the sought
      resonance becomes stable. The keystone is to extrapolate the attachment energy
      and not the total energy of the system. This method has the great advantage that
      the whole potential energy curve is obtained with quite good accuracy by the
      extrapolation. Limitations of the two techniques are discussed.

PMID- 15473718
TI  - Mixed-sector intermediate Hamiltonian Fock-space coupled cluster approach.
AB  - An alternative formulation of the intermediate Hamiltonian Fock-space coupled
      cluster scheme developed before is presented. The methodological and
      computational advantages of the new formulation include the possibility of using
      a model space with determinants belonging to different Fock-space sectors. This
      extends the scope of application of the multireference coupled cluster method,
      and makes possible the use of quasiclosed shells (e.g., p2, d4) as reference
      states. Representative applications are described, including electron affinities
      of group-14 atoms, ionization potentials of group-15 elements, and ionization
      potentials and excitation energies of silver and gold. Excellent agreement with
      experiment (a few hundredths of an electronvolt) is obtained, with significant
      improvement (by a factor of 5-10 for p3 states) over Fock-space coupled cluster
      results. Many states not reachable by the Fock-space approach can now be studied.

PMID- 15473719
TI  - Effective potential in density matrix functional theory.
AB  - In the previous paper it was shown that in the ground state the diagonal of the
      spin independent second-order density matrix n can be determined by solving a
      single auxiliary equation of a two-particle problem. Thus the problem of an
      arbitrary system with even electrons can be reduced to a two-particle problem.
      The effective potential of the two-particle equation contains a term v(p) of
      completely kinetic origin. Virial theorem and hierarchy of equations are derived
      for v(p) and simple approximations are proposed. A relationship between the
      effective potential u(p) of the shape function equation and the potential v(p) is
      established.

PMID- 15473720
TI  - Divide-and-conquer local correlation approach to the correlation energy of large
      molecules.
AB  - A divide-and-conquer local correlation approach for correlation energy
      calculations on large molecules is proposed for any post-Hartree-Fock correlation
      method. The main idea of this approach is to decompose a large system into
      various fragments capped by their local environments. The total correlation
      energy of the whole system can be approximately obtained as the summation of
      correlation energies from all capped fragments, from which correlation energies
      from all adjacent caps are removed. This approach computationally achieves linear
      scaling even for medium-sized systems. Our test calculations for a wide range of
      molecules using the 6-31G or 6-31G( * *) basis set demonstrate that this simple
      approach recovers more than 99.0% of the conventional second-order Moller-Plesset
      perturbation theory and coupled cluster with single and double excitations
      correlation energies.

PMID- 15473721
TI  - Time-dependent four-component relativistic density functional theory for
      excitation energies.
AB  - Time-dependent four-component relativistic density functional theory within the
      linear response regime is developed for calculating excitation energies of heavy
      element containing systems. Since spin is no longer a good quantum number in this
      context, we resort to time-reversal adapted Kramers basis when deriving the
      coupled Dirac-Kohn-Sham equation. The particular implementation of the formalism
      into the Beijing density functional program package utilizes the multipolar
      expansion of the induced density to facilitate the construction of the induced
      Coulomb potential. As the first application, pilot calculations on the valence
      excitation energies and fine structures of the rare gas (Ne to Rn) and Group 12
      (Zn to Hg) atoms are reported. To the best of our knowledge, it is the first time
      to be able to account for spin-orbit coupling within time-dependent density
      functional theory for excitation energies.

PMID- 15473722
TI  - Hamilton-Jacobi equation for the least-action/least-time dynamical path based on
      fast marching method.
AB  - Classical dynamics can be described with Newton's equation of motion or, totally
      equivalently, using the Hamilton-Jacobi equation. Here, the possibility of using
      the Hamilton-Jacobi equation to describe chemical reaction dynamics is explored.
      This requires an efficient computational approach for constructing the physically
      and chemically relevant solutions to the Hamilton-Jacobi equation; here we solve
      Hamilton-Jacobi equations on a Cartesian grid using Sethian's fast marching
      method. Using this method, we can--starting from an arbitrary initial
      conformation--find reaction paths that minimize the action or the time. The
      method is demonstrated by computing the mechanism for two different systems: a
      model system with four different stationary configurations and the H+H(2)-
      >H(2)+H reaction. Least-time paths (termed brachistochrones in classical
      mechanics) seem to be a suitable chioce for the reaction coordinate, allowing one
      to determine the key intermediates and final product of a chemical reaction. For
      conservative systems the Hamilton-Jacobi equation does not depend on the time, so
      this approach may be useful for simulating systems where important motions occur
      on a variety of different time scales.

PMID- 15473723
TI  - Multiresolution quantum chemistry in multiwavelet bases: Hartree-Fock exchange.
AB  - In a previous study we reported an efficient, accurate multiresolution solver for
      the Kohn-Sham self-consisitent field (KS-SCF) method for general polyatomic
      molecules. This study presents an efficient numerical algorithm to evalute
      Hartree-Fock (HF) exchange in the multiresolution SCF method to solve the HF
      equations. The algorithm employs fast integral convolution with the Poission
      kernel in the nonstandard form, screening the sparse multiwavelet representation
      to compute results of the integral operator only where required by the nonlocal
      exchange operator. Localized molecular obitals are used to attain near linear
      scaling. Results for atoms and molecules demonstrate reliable precision and
      speed. Calculations for small water clusters demonstrate a total cost to compute
      the HF exchange potential for all n(occ) occpuied MOs scaling as O(n(occ) (1.5)).

PMID- 15473724
TI  - Analysis of cooperativity and localization for atomic rearrangements.
AB  - We propose measures of localization and cooperativity for the analysis of atomic
      rearrangements. We show that for both clusters and bulk material cooperative
      rearrangements usually have significantly lower barriers than uncooperative ones,
      irrespective of the degree of localization. We also find that previous methods
      used to sample stationary points are biased towards rearrangements of particular
      types. Linear interpolation between local minima in double-ended transition state
      searches tends to produce cooperative rearrangements, while random perturbations
      of all the coordinates, as sometimes used in single-ended searches, have the
      opposite effect.

PMID- 15473725
TI  - Parallel, linear-scaling building-block and embedding method based on localized
      orbitals and orbital-specific basis sets.
AB  - We present a linear scaling method for the energy minimization step of
      semiempirical and first-principles Hartree-Fock and Kohn-Sham calculations. It is
      based on the self-consistent calculation of the optimum localized orbitals of any
      localization method of choice and on the use of orbital-specific basis sets. The
      full set of localized orbitals of a large molecule is seen as an orbital mosaic
      where each tessera is made of only a few of them. The orbital tesserae are
      computed out of a set of embedded cluster pseudoeigenvalue coupled equations
      which are solved in a building-block self-consistent fashion. In each iteration,
      the embedded cluster equations are solved independently of each other and, as a
      result, the method is parallel at a high level of the calculation. In addition to
      full system calculations, the method enables to perform simpler, much less
      demanding embedded cluster calculations, where only a fraction of the localized
      molecular orbitals are variational while the rest is frozen, taking advantage of
      the transferability of the localized orbitals of a given localization method
      between similar molecules. Monitoring single point energy calculations of large
      poly(ethylene oxide) molecules and three dimensional carbon monoxide clusters
      using an extended Huckel Hamiltonian are presented.

PMID- 15473726
TI  - Complete structural and magnetic characterization of biological radicals in
      solution by an integrated quantum mechanical approach: glycyl radical as a case
      study.
AB  - An integrated quantum mechanical approach for the structural and magnetic
      characterization of flexible free radicals in solution has been applied to a
      model of the glycyl radical engaged in peptidic chains. The hyperfine couplings
      computed using hybrid density functionals and purposely tailored basis sets are
      in good agreement with experiment when vibrational averaging effects from low
      frequency motions and solvent effects (both direct H bonding and bulk) are taken
      into the proper account. The g tensor shows a smaller dependence on the specific
      form of the density functional, the extension of the basis set over a standard
      double-zeta+polarization level, vibrational averaging, and bulk solvent effects.
      However, hydrogen bridges with solvent molecules belonging to the first solvation
      shell play a significant role. Together with their intrinsic interest, our
      results show that a comprehensive and reliable computational approach is becoming
      available for the complete characterization of open-shell systems of biological
      interest in their natural environment.

PMID- 15473727
TI  - Two-component relativistic methods for the heaviest elements.
AB  - Different generalized Douglas-Kroll transformed Hamiltonians (DKn, n=1, 2,...,5)
      proposed recently by Hess et al. are investigated with respect to their
      performance in calculations of the spin-orbit splittings. The results are
      compared with those obtained in the exact infinite-order two-component (IOTC)
      formalism which is fully equivalent to the four-component Dirac approach. This is
      a comprehensive investigation of the ability of approximate DKn methods to
      correctly predict the spin-orbit splittings. On comparing the DKn results with
      the IOTC (Dirac) data one finds that the calculated spin-orbit splittings are
      systematically improved with the increasing order of the DK approximation.
      However, even the highest-order approximate two-component DK5 scheme shows
      certain deficiencies with respect to the treatment of the spin-orbit coupling
      terms in very heavy systems. The meaning of the removal of the spin-dependent
      terms in the so-called spin-free (scalar) relativistic methods for many-electron
      systems is discussed and a computational investigation of the performance of the
      spin-free DKn and IOTC methods for many-electron Hamiltonians is carried out. It
      is argued that the spin-free IOTC rather than the Dirac-Coulomb results give the
      appropriate reference for other spin-free schemes which are based on approximate
      two-component Hamiltonians. This is illustrated by calculations of spin-free DKn
      and IOTC total energies, r(-1) expectation values, ionization potentials, and
      electron affinities of heavy atomic systems.

PMID- 15473728
TI  - Reactivity of C10H7+ and C10D7+ with H2 AND D2.
AB  - We have investigated, both theoretically and experimentally, the reactions of
      naphthylium C10H7+ and d-naphthylium C10D7+ ions with H2 and D2. Cross sections
      as functions of the collision energy have been measured for a variety of reaction
      channels. Theoretical calculations have been carried out at the density
      functional theory level which utilizes the hybrid functional B3LYP and the split
      valence 6-31G* basis set. The key features of the potential energy surfaces and
      the relevant thermochemical parameters have been calculated and they provide
      insights on the reaction mechanisms. The bimolecular reactivity of C10H7+ with H2
      is dominated by the production of naphthalene cation C10H8+. The reaction is not
      a direct atom-abstraction process, but instead it proceeds via the formation of a
      stable intermediate complex C10H9+ of sigma type geometry, with a significant
      mobility of hydrogen along the ring. This mobility allows the scrambling of the
      hydrogen atoms and causes the successive statistical fragmentation of the complex
      into a variety of product channels. Elimination of one H(D) atom appears to be
      favored over elimination of one H2 or HD molecule. Alternatively, the
      intermediate complex can be stabilized either by collision with a third body or
      by emission of a photon.

PMID- 15473729
TI  - Ab initio and kinetic calculations for the reactions of Cl with SiH(n)Cl(4-n)
      (n=1,2,3,4).
AB  - The direct hydrogen abstraction reactions of Cl atom with SiH(n)Cl(4-n)
      (n=1,2,3,4) have been studied systematically using ab initio molecular orbital
      theory. Geometries have been optimized at the MP2 level with 6-311+G(d) basis
      set, QCISD(T)/6-311+G(d,p) has been used in the final single point energy
      calculation. The kinetic calculations of these reactions have been explored using
      the canonical variational transition (CVT) state theory method with small
      curvature tunneling (SCT) effect correction over the temperature range of 200
      2000 K. The CVT/SCT rate constants exhibit typical non-Arrhenius behavior and
      three-parameter rate-temperature formulas have been fitted for the reactions of
      Cl with SiH4, SiH3Cl, SiH2Cl2, and SiHCl3, respectively (in unit of cm(3)
      molecule(-1) s(-1)). The calculated CVT/SCT rate constants are in agreement with
      the available experimental values.

PMID- 15473730
TI  - Cyclic-N3. I. An accurate potential energy surface for the ground doublet
      electronic state up to the energy of the 2A2/2B1 conical intersection.
AB  - A sophisticated adiabatic ground electronic state potential energy surface for a
      pure nitrogen ring (cyclic-N3) molecule is constructed based on extensive high
      level ab initio calculations and accurate three-dimensional spline
      representation. Most of the important features of the potential energy surface
      are presented using various reduced dimensionality slices in internal
      hyperspherical coordinates as well as full dimensional isoenergy surfaces. Very
      significant geometric phase effects are predicted in the spectra of rotational
      vibrational states of cyclic-N3.

PMID- 15473731
TI  - The effect of kinematic parameters on inelastic scattering of glyoxal.
AB  - The effect of kinematic parameters (relative velocity v(rel), relative momentum
      p(rel), and relative energy E(rel)) on the rotational and rovibrational inelastic
      scatterings of 0(0)K(0)S(1) trans-glyoxal has been investigated by colliding
      glyoxal seeded in He or Ar with target gases D2, He, or Ne at different
      scattering angles in crossed supersonic beams. The inelastic spectra for target
      gases He and D2 acquired with two different sets of kinematic parameters revealed
      no significant differences. This result shows that kinematic factors have the
      major influence in the inelastic scattering channel competition whereas the
      intermolecular potential energy surface plays only a secondary role. The well
      defined exponential dependence of relative cross sections on exchanged angular
      momentum identifies angular momentum as the dominant kinematic factor in
      collision-induced rotationally and rovibrationally inelastic scatterings. This is
      supported by the behavior of the relative inelastic cross sections data in a
      "slope-p(rel)" representation. In this form, the data show a trend nearly
      independent of the target gas identity. Representations involving E(rel) and
      v(rel) show trends specific to the target gas.

PMID- 15473732
TI  - Orbital alignment in N2O photodissociation. I. Determination of all even rank
      anisotropy parameters.
AB  - We present a general method for determination of the photofragment K=4 state
      multipoles in an ion imaging experiment. These multipoles are important for
      determining the full density matrix for any photofragment with j(a)> or =2. They
      are expressed in terms of laboratory frame anisotropy parameters that have
      distinct physical origins and possess characteristic angular distributions. The
      explicit expression for the (2+1) resonant multiphoton ionization absorption
      signal for the case of arbitrarily polarized probe light is derived and a
      procedure for isolation of the rank-4 state multipoles from all others is shown.
      This treatment is applied to the case of O((1)D) produced in the 193 nm
      photodissociation of N2O. The results show nonzero values for all K=4 anisotropy
      parameters, indicating the complexity of the photodissociation dynamics in this
      system.

PMID- 15473733
TI  - Ambiguities in the semiclassical assignment of the asymmetric rotor rotational
      quantum numbers.
AB  - The semiclassical quantization of the rigid asymmetric rotor is revisited in the
      context of classical inelastic collisions. It is shown that the standard bin
      histogram method, widely used in quasiclassical trajectory calculations involving
      linear target molecules, cannot be generalized to the case of asymmetric top
      molecules owing to ambiguities in the assignment of the final classical action to
      a particular rotational quantum state. These ambiguities result from pairs of
      states which are indistinguishable within the bin histogram approach at all the
      common levels of semiclassical theory. A single value of the classical action can
      thus correspond to two different quantum states, preventing the distinction
      between these states in the calculation of rotational cross sections. Our results
      are illustrated for the rotational states J=1-4 of the water molecule at its
      equilibrium geometry.

PMID- 15473734
TI  - Gas phase detection of cyclic B3: 2(2)E' <-- X2A1' electronic origin band.
AB  - The rotationally resolved origin band in the 2(2)E'<--X2A1' electronic spectrum
      of cyclic B3 has been observed by cavity ring down spectroscopy in the gas phase.
      The B3 molecule was generated in a supersonic planar plasma containing decaborane
      (B10H14) and neon as a carrier gas. The rotational structure pattern is that of a
      cyclic molecule. It is analyzed assuming an equilateral triangle in both
      electronic states. The band origin is determined to be 21 853.52 cm(-1), and the
      bond lengths 1.603 77(106) A in the ground and 1.619 07(96) A in the excited
      electronic state are inferred from analysis of the rotational structure.

PMID- 15473735
TI  - Photoassociation spectroscopy of ultracold Cs below the 6P(3/2) limit.
AB  - High precision photoassociation spectroscopy is performed in ultracold cesium
      gas, with detunings as large as 51 cm(-1) below the Cs(6S(1/2))+Cs(6P(3/2))
      asymptote. Trap-loss fluorescence detection is used for detecting the
      photoassociation to excited state ultracold molecules. Long vibrational
      progressions are assigned to electronic states of 0(g) (-), 0(u) (+), and 1(g)
      symmetry. The spectral data are fitted to a LeRoy-Bernstein equation, in order to
      obtain the effective coefficients of the leading long-range interaction term
      (C(3)/R(3)) and the relative vibrational quantum numbers measured down from
      dissociation. Additionally we present evidence for perturbations between the 0(g)
      (-) state and the dark 2(u) state.

PMID- 15473736
TI  - Periodic table of 3d-metal dimers and their ions.
AB  - The ground states of the mixed 3d-metal dimers TiV, TiCr, TiMn, TiFe, TiCo, TiNi,
      TiCu, TiZn, VCr, VMn, VFe, VCo, VNi, VCu, VZn, CrMn, CrFe, CrCo, CrNi, CrCu,
      CrZn, MnFe, MnCo, MnNi, MnCu, MnZn, FeCo, FeNi, FeCu, FeZn, CoNi, CoCu, CoZn,
      NiCu, NiZn, and CuZn along with their singly negatively and positively charged
      ions are assigned based on the results of computations using density functional
      theory with generalized gradient approximation for the exchange-correlation
      functional. Except for TiCo and CrMn, our assignment agrees with experiment.
      Computed spectroscopic constants (r(e),omega(e),D(o)) are in fair agreement with
      experiment. The ground-state spin multiplicities of all the ions are found to
      differ from the spin multiplicities of the corresponding neutral parents by +/-1.
      Except for TiV, MnFe, and MnCu, the number of unpaired electrons, N, in a neutral
      ground-state dimer is either N(1)+N(2) or mid R:N(1)-N(2)mid R:, where N(1) and
      N(2) are the numbers of unpaired 3d electrons in the 3d(n)4s(1) occupation of the
      constituent atoms. Combining the present and previous results obtained at the
      same level of theory for homonuclear 3d-metal and ScX (X=Ti-Zn) dimers allows one
      to construct "periodic" tables of all 3d-metal dimers along with their singly
      charged ions.

PMID- 15473737
TI  - Relativistic effects on nuclear magnetic shielding constants in HX and CH3X
      (X=Br,I) based on the linear response within the elimination of small component
      approach.
AB  - Numerical calculations of relativistic effects on nuclear magnetic shielding
      constants sigma corresponding to all one-body operators obtained within a
      formalism developed in previous work were carried out. In this formalism, the
      elimination of small component scheme is applied to evaluate all quantities
      entering a four-component RSPT(2) expression of magnetic molecular properties. HX
      and CH3X (X=Br,I) were taken as model compounds. Calculations were carried out at
      the Hartree-Fock level for first-order quantities, and at the random-phase
      approximation (RPA) level for second- and third-order ones. It was found that
      values of sigma(X) are largely affected by several relativistic corrections not
      previously considered in the bibliography. sigma Values of the H nucleus are in
      close agreement with four-component RPA ones. Overall relativistic effects on the
      shift of sigma(X) from HX to CH3X are smaller than the nonrelativistic shifts.

PMID- 15473738
TI  - Ab initio rate constants from hyperspherical quantum scattering: application to
      H+C2H6 and H+CH3OH.
AB  - The dynamics and kinetics of the abstraction reactions of H atoms with ethane and
      methanol have been studied using a quantum mechanical procedure. Bonds being
      broken and formed are treated with explicit hyperspherical quantum dynamics. The
      ab initio potential energy surfaces for these reactions have been developed from
      a minimal number of grid points (average of 48 points) and are given by
      analytical functionals. All the degrees of freedom except the breaking and
      forming bonds are optimized using the second order perturbation theory method
      with a correlation consistent polarized valence triple zeta basis set. Single
      point energies are calculated on the optimized geometries with the coupled
      cluster theory and the same basis set. The reaction of H with C2H6 is endothermic
      by 1.5 kcal/mol and has a vibrationally adiabatic barrier of 12 kcal/mol. The
      reaction of H with CH3OH presents two reactive channels: the methoxy and the
      hydroxymethyl channels. The former is endothermic by 0.24 kcal/mol and has a
      vibrationally adiabatic barrier of 13.29 kcal/mol, the latter reaction is
      exothermic by 7.87 kcal/mol and has a vibrationally adiabatic barrier of 8.56
      kcal/mol. We report state-to-state and state-selected cross sections together
      with state-to-state rate constants for the title reactions. Thermal rate
      constants for these reactions exhibit large quantum tunneling effects when
      compared to conventional transition state theory results. For H+CH3OH, it is
      found that the CH2OH product is the dominant channel, and that the CH3O channel
      contributes just 2% at 500 K. For both reactions, rate constants are in good
      agreement with some measurements.

PMID- 15473739
TI  - Reactions of N+, N2+, and N3+ with NO from 300 to 1400 K.
AB  - Rate constants have been measured from 300 to 1400 K in a selected ion flow tube
      (SIFT) and a high temperature flowing afterglow for the reactions of N+, N2+ and
      N3+ with NO. In all of the systems, the rate constants are substantially less
      than the collision rate constant. Comparing the high temperature results to
      kinetics studies as a function of translational energy show that all types of
      energy (translational, rotational, and vibrational) affect the reactivity
      approximately equally for all three ions. Branching ratios have also been
      measured at 300 and 500 K in a SIFT for the N+ and N3+ reactions. An increase in
      the N2+ product at the expense of NO+ nondissociative charge transfer product
      occurs at 500 K with N+. The branching ratios for the reaction of N3+ with NO
      have also been measured in the SIFT, showing that only nondissociative charge
      transfer giving NO+ occurs up to 500 K. The current results are discussed in the
      context of the many previous studies of these ions in the literature.

PMID- 15473740
TI  - Insights into dynamics of the S2 state of thiophosgene from ab initio
      calculations.
AB  - The S2 potential energy surface for Cl2CS dissociation has been characterized
      with a combined complete active space self-consistent field and multireference
      configuration interaction method. The S3/S2 minimum-energy intersection has been
      determined with the state-averaged complete active space self-consistent field
      method. The S2 direct dissociation was found to have a barrier of 6.0 kcal/mol,
      leading to formation of Cl(X2P)+ClCS(A2A") in the excited electronic state.
      Dynamics of the S2 state of Cl2CS can be summarized as follows: (1) The S2-S0
      fluorescence occurs with high quantum yield at low excess energies; (2) Both the
      S(2) dissociation and the S2-->S3 internal conversion cause the loss of the S2-S0
      fluorescence upon photoexcitation at 235-253 nm; (3) The S2-->S3 internal
      conversion (IC) followed by the direct IC to the ground electronic state results
      in the fragments produced in the ground state, while the S2 dissociation leads to
      formation of the fragments in excited electronic states.

PMID- 15473741
TI  - Circular dichroism effect for linear molecules induced by a resonant circularly
      polarized pumping optical field.
AB  - In this paper we propose and discuss the laser-induced circular dichroism (LICD)
      effect, which is expected to occur in linear molecules pumped by a strong
      circular resonant light beam. The effect is to be detected via the absorption of
      a weak circularly polarized probe beam on another transition. Analogous to the
      external magnetic field in magnetic circular dichroism the resonant circular
      polarized pumping optical field can induce the nonzero antisymmetric rotational
      polarizabilities of a linear molecule, and cause the LICD effect. LICD contains
      three distinct contributions from M-dependent splittings of the sublevels mid
      R:JM due to the ac Stark effect, from the differences of Boltzmann statistical
      distributions among the ground state sublevels mid R:JM due to the ac Stark
      splittings, and from the changes of occupation probability in rotational
      sublevels mid R:JM due to the pumping effect. The fundamental formulas for the
      above three terms of LICD have been deduced by the density matrix method. As an
      example, the LICD for CO molecules have been calculated. The results indicate
      that in comparison with the rotationally resolved magnetic vibrational circular
      dichroism experiment, LICD may be measurable and form a basis of a different kind
      of CD spectroscopy.

PMID- 15473742
TI  - Motional narrowing of the rotational spectrum of trifluoropropyne at 6550 cm(-1)
      by intramolecular vibrational energy redistribution.
AB  - We present the basic principles of dynamic rotational spectroscopy for the highly
      vibrationally excited symmetric top molecule trifluoropropyne (TFP,CF3CCH).
      Single molecular eigenstate rotational spectra of TFP were recorded in the region
      of the first overtone of the nu(1) acetylenic stretching mode at 6550 cm(-1) by
      infrared-pulsed microwave-Fourier transform microwave triple resonance
      spectroscopy. The average rotational constant (B) of the highly vibrationally
      mixed quantum states at 6550 cm(-1) is 2909.33 MHz, a value that is 40 MHz larger
      than the rotational constant expected for the unperturbed C-H stretch overtone
      (2869.39 MHz). The average rotational constant and rotational line shape of the
      molecular eigenstate rotational spectra are compared to the distribution of
      rotational constants expected for the ensemble of normal-mode vibrational states
      at 6550 cm(-1) that can interact by intramolecular vibrational energy
      redistribution (IVR). The normal-mode population distribution at 6550 cm(-1) can
      be described using a Boltzmann distribution with a microcanonical temperature of
      1200 K. At this energy the rotational constant distribution in the normal-mode
      basis set is peaked at about 2910 MHz with a width of about 230 MHz. The
      distribution is slightly asymmetric with a tail to the high end. The
      experimentally measured dynamic rotational spectra are centered at the normal
      mode distribution peak; however, the spectral width is significantly narrower (40
      MHz) than normal-mode ensemble width (230 MHz). This reduction of the width,
      along with the Lorentzian shape of the eigenstate rotational spectra when
      compared to the Gaussian shape of the calculated ensemble distribution,
      illustrates the narrowing of the spectrum due to IVR exchange. The IVR exchange
      rate was determined to be 120 ps, about ten times faster than the rate at which
      energy is redistributed from the v=2 level of the acetylenic stretch.

PMID- 15473743
TI  - Optical spectroscopy of RuC: 18,000-24,000 cm(-1).
AB  - The optical spectrum of diatomic RuC has been recorded from 17 800 to 24 200 cm(
      1). Three previously unidentified excited electronic states were analyzed and
      identified as having Omega' = 0, Omega' = 2, and Omega' = 3. The Omega' = 3 state
      was determined to be a 3Delta3 state that is suggested to arise from a mixture of
      the 10sigma(2)11sigma(2)5pi(3)2delta(3)12sigma(1)6pi(1) and
      10sigma(2)11sigma(1)5pi(3)2delta(3)12sigma(2)6pi(1) electronic configurations.
      Three additional bands belonging to the previously observed [18.1] (1)Pi<--X
      (1)Sigma(+) system were analyzed to obtain B(e) (')=0.558 244(48) cm(-1),
      alpha(e) (')=0.004 655(27) cm(-1), omegae' = 887.201(37) cm(-1), and omega(e)
      'xe' = 5.589(7) cm(-1) for the 102Ru 12C isotopomer (1sigma error limits). A
      Rydberg-Klein-Rees analysis was then performed using the determined spectroscopic
      constants of the [18.1] 1Pi state, and similar analyses were performed for the
      previously observed states. The resulting potential energy curves are provided
      for the 100Ru 12C, 101Ru 12C, 102Ru 12C, and 104Ru 12C isotopic species.

PMID- 15473744
TI  - Laser-induced fluorescence of cyclohexadienyl (c-C6H7) radical in the gas phase.
AB  - A laser-induced fluorescence spectrum was observed in the 500-560 nm region when
      a mixture of 1,4-cyclohexadiene and oxalyl chloride was photolyzed at 193 nm. The
      observed excitation spectrum was assigned to the A (2)A(2)<--X (2)B(1) transition
      of the cyclohexadienyl radical c-C6H7, produced by abstraction of a hydrogen atom
      from 1,4-cyclohexadiene by Cl atoms. The origin of the A<--X transition of c
      C(6)H(7) was at 18 207 cm(-1). From measurements of the dispersed fluorescence
      spectra and ab initio calculations, the frequencies of several vibrational modes
      in both the ground and excited states of c-C(6)H(7) were determined: nu(5)(C-H in
      plane bend)=1571, nu(8)(C-H in-plane bend)=1174, nu(10)(C-C-C in-plane bend)=981,
      nu(12)(C-C-C in-plane bend)=559, nu(16)(C-C-C out-of-plane bend)=375, and
      nu(33)(C-C-C in-plane bend)=600 cm(-1) for the ground state and nu(8)=1118,
      nu(10)=967, nu(12)=502, nu(16)=172, and nu(33)=536 cm(-1) for the excited states.

PMID- 15473745
TI  - High resolution infrared spectra of helium clusters seeded with isotopic carbon
      monoxide, HeN-13C 16O and HeN-12C 18O.
AB  - Infrared spectra of isotopically substituted HeN-CO clusters (1 < N < 19) have
      been studied in order to extend the original results on the normal isotope. The
      same two series of R(0) transitions were observed, correlating with the a- and b
      type transitions of He1-CO, with only small shifts in relative position. The
      previously obscured a-type line for He6-CO was detected. Examination of the small
      shifts among isotopomers showed remarkably smooth behavior, except in the
      "unstable" regions around N=7 (b-type series) and 15 (a-type series). The overall
      results firmly support the assignments and analysis given for the normal isotope.

PMID- 15473746
TI  - Global potential energy surfaces for the Al+(1S) + H2 system.
AB  - Global, three-dimensional multireference ab initio potential energy surfaces have
      been calculated for the AlH2+ system for the two lowest energy singlet states and
      the lowest energy triplet state. These surfaces were calculated using the
      multireference configuration interaction level of theory with a large basis set.
      The accuracy of the surfaces were checked against available experimental data and
      previous theoretical investigations. The areas of surface crossings between the
      ground state singlet surface and the lowest energy triplet surface and the first
      excited singlet surface have been thoroughly investigated in all three dimensions
      and found to give rise to two regions of surface crossings--an "early" crossing
      (reduced H2 distance) and a "late" crossing (enlarged H2 distance). It is
      anticipated that both of these crossings will be important in modeling the
      dynamics of the system. Each of the global potential energy surfaces were fit by
      interpolation methodology to obtain analytic representations of the surfaces. A
      representative classical simulation on the ground state singlet surface was
      performed and discussed.

PMID- 15473747
TI  - Higher virial coefficients of four and five dimensional hard hyperspheres.
AB  - The seventh and eighth virial coefficients for hard hyperspheres are calculated
      by Monte Carlo techniques. It is found that B(7)/B(2) (6)=0.001 43+/-0.000 13 and
      0.000 44+/-0.000 12 in four and five dimensions, respectively, and that B(8)/B(2)
      (7)=0.000 414+/-0.000 20 in four dimensions. These values are used to investigate
      various proposed equations of state. Comparisons against the molecular dynamics
      calculations of Luban and Michels show that their proposed semiempirical form is
      excellent at higher densities. Moreover, we confirm Santos observation in five
      dimensions that a suitable linear combination of the Percus-Yevick
      compressibility and virial equations of state fits the molecular dynamics data
      nearly as well as any other proposed form.

PMID- 15473748
TI  - Liquid-gas coexistence and critical point shifts in size-disperse fluids.
AB  - Specialized Monte Carlo simulations and the moment free energy (MFE) method are
      employed to study liquid-gas phase equilibria in size-disperse fluids. The
      investigation is made subject to the constraint of fixed polydispersity, i.e.,
      the form of the "parent" density distribution rho(0)(sigma) of the particle
      diameters sigma, is prescribed. This is the experimentally realistic scenario
      for, e.g., colloidal dispersions. The simulations are used to obtain the cloud
      and shadow curve properties of a Lennard-Jones fluid having diameters distributed
      according to a Schulz form with a large (delta approximately 40%) degree of
      polydispersity. Good qualitative accord is found with the results from a MFE
      method study of a corresponding van der Waals model that incorporates size
      dispersity both in the hard core reference and the attractive parts of the free
      energy. The results show that polydispersity engenders considerable broadening of
      the coexistence region between the cloud curves. The principal effect of
      fractionation in this region is a common overall scaling of the particle sizes
      and typical interparticle distances, and we discuss why this effect is rather
      specific to systems with Schulz diameter distributions. Next, by studying a
      family of such systems with distributions of various widths, we estimate the
      dependence of the critical point parameters on delta. In contrast to a previous
      theoretical prediction, size dispersity is found to raise the critical
      temperature above its monodisperse value. Unusually for a polydisperse system,
      the critical point is found to lie at or very close to the extremum of the
      coexistence region in all cases. We outline an argument showing that such
      behavior will occur whenever polydispersity affects only the range, rather than
      the strength of the interparticle interactions.

PMID- 15473749
TI  - Nucleation versus spinodal decomposition in phase formation processes in
      multicomponent solutions.
AB  - In the present paper, some further results of application of the generalized
      Gibbs' approach to describing new-phase formation processes are outlined. The
      path of cluster evolution in size and composition space is determined taking into
      account both thermodynamic and kinetic factors. The basic features of these paths
      of evolution are discussed in detail for a simple model of a binary mixture.
      According to this analysis, size and composition of the clusters of the newly
      evolving phase change in an unexpected way which is qualitatively different as
      compared to the classical picture of nucleation-growth processes. As shown,
      nucleation (i.e., the first stage of cluster formation starting from metastable
      initial states) exhibits properties resembling spinodal decomposition (the size
      remains nearly constant while the composition changes) although the presence of
      an activation barrier distinguishes the nucleation process from true spinodal
      decomposition. In addition, it is shown that phase formation both in metastable
      and unstable initial states near the classical spinodal may proceed via a passage
      of a ridge of the thermodynamic potential with a finite work of the activation
      barrier even though (for unstable initial states) the value of the work of
      critical cluster formation (corresponding to the saddle point of the
      thermodynamic potential) is zero. This way, it turns out that nucleation concepts
      in a modified form as compared with the classical picture-may govern also phase
      formation processes starting from unstable initial states. In contrast to the
      classical Gibbs' approach, the generalized Gibbs' method provides a description
      of phase changes both in binodal and spinodal regions of the phase diagram and
      confirms the point of view assuming a continuity of the basic features of the
      phase transformation kinetics in the vicinity of the classical spinodal curve.

PMID- 15473750
TI  - Rescaled density expansions and demixing in hard-sphere binary mixtures.
AB  - The demixing transition of a binary fluid mixture of additive hard spheres is
      analyzed for different size asymmetries by starting from the exact low-density
      expansion of the pressure. Already within the second virial approximation the
      fluid separates into two phases of different composition with a lower consolute
      critical point. By successively incorporating the third, fourth, and fifth virial
      coefficients, the critical consolute point moves to higher values of the pressure
      and to lower values of the partial number fraction of the large spheres. When the
      exact low-density expansion of the pressure is rescaled to higher densities as in
      the Percus-Yevick theory, by adding more exact virial coefficients a different
      qualitative movement of the critical consolute point in the phase diagram is
      found. It is argued that the Percus-Yevick factor appearing in many empirical
      equations of state for the mixture has a deep influence on the location of the
      critical consolute point, so that the resulting phase diagram for a prescribed
      equation has to be taken with caution.

PMID- 15473751
TI  - Evaluation of site-site bridge diagrams for molecular fluids.
AB  - The presence of bridge functions in formally exact integral equation theories is
      the primary obstacle preventing the extraction of exact fluid structure from
      these theories. The bridge functions are typically neglected but in many fluids
      their impact may be significant. Each bridge function can be subdivided into
      bridge diagrams, which are well defined but difficult to evaluate. The
      calculation of bridge diagrams for the Chandler-Silbey-Ladanyi (CSL) integral
      equation theory is the subject of this paper. In particular, we evaluate the
      diagrams required to yield an exact theory up to the first power in density
      [O(rho(1))] and provide algorithms that remain feasible for any molecule.
      Further, the bridge diagrams are evaluated and compared with the f-bond and h
      bond formulations. Exact bridge diagrams are numerically evaluated for several
      chiral molecules, for two polar dimers, and for SPC/E water. The quality of the
      diagrams is assessed in two ways: First, the predicted interatomic distributions
      are compared with those obtained from Monte Carlo simulations. Second, the
      connectivity constraints are evaluated and the errors in satisfying these exact
      relationships are compared for the f-bond and h-bond formulations. For apolar
      fluids, a clear improvement in CSL theory is evident with the inclusion of
      O(rho(0)) and O(rho(1)) diagrams. In contrast, for polar fluids, the inclusion of
      bridge diagrams does not lead to improvement in the structural predictions.

PMID- 15473752
TI  - Sublimation enthalpy of dye molecules measured using fluorescence.
AB  - We present an in-flight fluorescence detection scheme for molecular beams which
      is applied to determine the enthalpy of sublimation of dye molecules. We
      investigate tetraphenylporphyrin (TPP), porphine, and nile red, which are
      believed to be suitable candidates for molecular de Broglie wave interferometry.
      The measured values are H(sub)(TPP)=142+/-3 kJ/mol, H(sub)(porphine)=87+/-3
      kJ/mol, and H(sub)(nile red)=66+/-2 kJ/mol. For TPP, sublimation enthalpies
      differ in the literature by more than a factor of 2. Our measurements confirm a
      value at the lower end of this scale. We discuss changes in the character of the
      molecular flow with the source temperature as a prime reason for discrepancies in
      the published data.

PMID- 15473753
TI  - Local order and dynamics in supercooled water: a study by IR spectroscopy and
      molecular dynamic simulations.
AB  - Micron-sized water droplets in a cryogenic flow tube were probed by IR
      spectroscopy. The analysis of the IR spectra suggests that there is a relative
      increase of about 30% in the fraction, f(L), of low density domains in water on
      cooling over the temperature range between 300 and 240 K. The results derived
      from the experiments agree qualitatively with those of molecular dynamics (MD)
      simulations in terms of the increase in the f(L) values. The MD simulations show
      that the intensities of the mode at about 100 cm(-1) for the molecules in the low
      density domains are reduced in comparison to the average, while the intensities
      and frequencies of the librational mode at 600 cm(-1) are increased. Furthermore,
      the reorientations (dielectric relaxation times) in these domains are found to be
      somewhat slower, pointing to the fact that these low density "cages" live longer
      than the average local molecular environments in supercooled water.

PMID- 15473754
TI  - Solvation dynamics in supercritical fluids: equilibrium versus nonequilibrium
      solvent response functions.
AB  - We present a theoretical study of solvation dynamics in supercritical fluids.
      Molecular dynamics simulations show a significant difference between equilibrium
      and nonequilibrium solvent response functions, especially pronounced at medium
      and low solvent densities. We propose an analytical theory for the nonequilibrium
      solvation function based on the generalized nonlinear Smoluchowski-Vlasov
      equation. The theory is shown to be in good agreement with simulation, providing
      an accurate description of the nonequilibrium time-dependent solvent density
      profile around the solute over a wide range of supercritical solvent densities.
      The nonequilibrium solvent response function is shown to reflect gradual solvent
      clustering around the excited solute.

PMID- 15473755
TI  - Evidence for the coexistence of two different mechanisms for the occurrence of
      anti-Kasha S2 (1 (1)Bu) fluorescence from alpha,omega-diphenylpolyenes.
AB  - Fluorescence, fluorescence excitation, and absorption spectra have been measured
      for diphenylpolyenes with the polyene double bond number (n) from three to seven
      in solvents with different polarizabilities at room temperature. These polyenes
      exhibit anti-Kasha S(2) (1 (1)B(u)) fluorescence beside conventional S(1) (2
      (1)A(g)) fluorescence in room temperature solution. It is shown that there are
      two different mechanisms for occurrence of the S(2) (1 (1)B(u)) fluorescence of
      diphenylpolyenes. S(2) fluorescence occurs through the thermal population of the
      S(1) state for the shorter diphenylpolyenes (n=3 and 4), while it occurs as
      prompt S(2) fluorescence due to inefficient S(2)-->S(1) internal conversion for
      the longer diphenylpolyenes (n=6 and 7). With diphenyldecapentaene (n=5), S(2)
      fluorescence based on both mechanisms is observed depending on the polarizability
      of the solvent used. The present results provide deeper insight into the
      mechanism for the occurrence of anti-Kasha S(2) fluorescence of polyenes.

PMID- 15473756
TI  - Calculation of infrared absorption spectra using Gaussian variational wave
      packets.
AB  - Formulas are developed for calculation of infrared absorption spectra with the
      help of Gaussian variational wave packets. The excitation is viewed as occurring
      to a linear combination of basis states corresponding to a Gaussian multiplied by
      Hermite polynomials of coordinates. Application of the formulas is examplified on
      HDO isolated in a D2O matrix. A simple approximation is proposed for the
      fundamental transitions.

PMID- 15473757
TI  - Organic functionalization of sidewall of carbon nanotubes.
AB  - Using density functional theory, we have theoretically studied sidewall
      functionalization of carbon nanotubes (CNT) with a nucleophilic organic carbene,
      dipyridyl imidazolidene (DPI). When compared to the dissociated system, formation
      of the adduct from defect-free (5,5) tube and the DPI is weakly exothermic.
      However, introduction of (5,7,7,5) defect or nitrogen doping at the CNT
      stabilizes the adduct in both physical and chemical senses, suggesting a possible
      way to enrich the chemistry of sidewall functionalization. The work function of
      the adducts is found to decrease by approximately 0.4 eV per DPI/80 atoms. Upon
      binding of the DPI, electronic structures are modified in such a way that small
      gaps are introduced, where the size of the gap depends upon the degree of
      functionalization.

PMID- 15473758
TI  - The growth of perylene on Ru(0001).
AB  - The structure of perylene adsorbed on Ru(0001) surface has been studied by
      ultraviolet photoemission spectroscopy (UPS) and low-energy electron diffraction.
      An ordered p(4x4) structure is observed from a monolayer (about 4 A thickness) of
      the perylene on Ru(0001) surface. UPS measurements show the molecular features,
      from the perylene multiplayer, between 2 and 10 eV below the Fermi level. Angle
      resolved ultraviolet photoemission spectroscopy measurements suggest that the
      perylene molecular plane is parallel to the substrate. Temperature dependent UPS
      measurements show that the perylene multilayer is stable on Ru(0001) surface up
      to 125 degrees C. The desorption of the multilayer and the decomposition of the
      monolayer are observed above 125 degrees C.

PMID- 15473759
TI  - Anomalous viscoelasticity near the isotropic-nematic phase transition in liquid
      crystals.
AB  - Recent optical Kerr effect experiments have shown that orientational relaxation
      of nematogens shows a pronounced slow down of the response function at
      intermediate times and also a power law decay near the isotropic-nematic (I-N)
      transition. In many aspects, this behavior appears to be rather similar to the
      ones observed in the supercooled liquid near-glass transition. We have performed
      molecular dynamics simulations of model nematogens (Gay-Berne with aspect ratio
      3) to explore the viscoelasticity near the I-N transition and also investigated
      the correlation of viscoelasticity (if any) with orientational relaxation. It is
      found that although the viscosity indeed undergoes a somewhat sharper than normal
      change near the I-N transition, it is not characterized by any divergence-like
      behavior (like the ones observed in the supercooled liquid). The rotational
      friction, on the other hand, shows a much sharper rise as the I-N transition is
      approached. Interestingly, the probability distribution of the amplitude of the
      three components of the stress tensor shows anisotropy near the I-N transition
      similar anisotropy has also been seen in the deeply supercooled liquid. Frequency
      dependence of viscosity shows several unusual behaviors: (a) There is a weak,
      power law dependence on frequency [eta(')(omega) approximately omega(-alpha)] at
      low frequencies and (b) there is a rapid increase in the sharp peak observed in
      eta(')(omega) in the intermediate frequency on approach to the I-N transition
      density. These features can be explained from the stress-stress time correlation
      function. The angular velocity correlation function also exhibits a power law
      decay in time. The reason for this is discussed.

PMID- 15473760
TI  - Structure, surface excess and effective interactions in polymer nanocomposite
      melts and concentrated solutions.
AB  - The Polymer Reference Interaction Site Model (PRISM) theory is employed to
      investigate structure, effective forces, and thermodynamics in dense polymer
      particle mixtures in the one and two particle limit. The influence of particle
      size, degree of polymerization, and polymer reduced density is established. In
      the athermal limit, the surface excess is negative implying an entropic dewetting
      interface. Polymer induced depletion interactions are quantified via the particle
      particle pair correlation function and potential of mean force. A transition from
      (nearly) monotonic decaying, attractive depletion interactions to much stronger
      repulsive-attractive oscillatory depletion forces occurs at roughly the
      semidilute-concentrated solution boundary. Under melt conditions, the depletion
      force is extremely large and attractive at contact, but is proceeded by a high
      repulsive barrier. For particle diameters larger than roughly five monomer
      diameters, division of the force by the particle radius results in a nearly
      universal collapse of the depletion force for all interparticle separations.
      Molecular dynamics simulations have been employed to determine the depletion
      force for nanoparticles of a diameter five times the monomer size over a wide
      range of polymer densities spanning the semidilute, concentrated, and melt
      regimes. PRISM calculations based on the spatially nonlocal hypernetted chain
      closure for particle-particle direct correlations capture all the rich features
      found in the simulations, with quantitative errors for the amplitude of the
      depletion forces at the level of a factor of 2 or less. The consequences of
      monomer-particle attractions are briefly explored. Modification of the polymer
      particle pair correlations is relatively small, but much larger effects are found
      for the surface excess including an energetic driven transition to a wetting
      polymer-particle interface. The particle-particle potential of mean force
      exhibits multiple qualitatively different behaviors (contact aggregation, steric
      stabilization, local bridging attraction) depending on the strength and spatial
      range of the polymer-particle attraction.

PMID- 15473761
TI  - Molecular dynamics simulations of the d(CCAACGTTGG)(2) decamer in crystal
      environment: comparison of atomic point-charge, extra-point, and polarizable
      force fields.
AB  - Molecular dynamics simulations of the DNA duplex d(CCAACGTTGG)(2) were used to
      study the relationship between DNA sequence and structure in a crystal
      environment. Three different force fields were used: a traditional description
      based on atomic point charges, a polarizable force field, and an "extra-point"
      force field (with additional charges on extranuclear sites). It is found that all
      the force fields reproduce fairly well the sequence-dependent features of the
      experimental structure. The polarizable force field, however, provides the most
      accurate representation of the crystal structure and the sequence-dependent
      effects observed in the experiment. These results point out to the need of the
      inclusion of polarization for accurate descriptions of DNA.

PMID- 15473762
TI  - Structure and phase behavior of polyelectrolyte star solutions.
AB  - Using the recently developed effective interaction potentials between
      polyelectrolyte stars, we examine the structure and phase behavior of solutions
      of the same. The effective interaction is ultrasoft and density dependent, owing
      to the integration of the counterionic degrees of freedom. The latter contribute
      extensive volume terms that must be taken into account in drawing the phase
      diagram of the system. The structural behavior of the uniform fluid is
      characterized by anomalous structure factors, akin to those found previously for
      solutions of uncharged star polymers. The phase diagram of the system is very
      rich, featuring a fluid phase at low arm numbers of the stars, two reentrant
      melting regions, as well as a variety of crystal structures with unusual
      symmetry. The physical origin of these features can be traced back to the
      ultrasoft nature of the effective interaction potential.

PMID- 15473764
TI  - Characterization of the hyperline of D1/D0 conical intersections between the
      maleic acid and fumaric acid anion radicals.

PMID- 15473763
TI  - Self-diffusion of rodlike and spherical particles in a matrix of charged
      colloidal spheres: a comparison between fluorescence recovery after
      photobleaching and fluorescence correlation spectroscopy.
AB  - The fluorescence recovery after photobleaching (FRAP) method and the fluorescence
      correlation spectroscopy (FCS) have been applied on suspensions of highly charged
      colloidal spheres with a small content of rod-shaped tobacco mosaic virus (TMV)
      particles. Since these methods only determine the self-diffusion coefficient of
      the fluorescently labeled species, D(S) of the rods and the spheres could
      independently be measured. The ionic strength of the dispersion medium has been
      varied to measure self-diffusion of rods and spheres in dependence on the degree
      of order of the matrix spheres. In contrast to FRAP, which allows the
      determination of the long-time self-diffusion coefficient D(S) (L), FCS measures
      self-diffusion on a shorter time scale. Thus a comparison of the results that
      were obtained by FCS and FRAP, in combination with Brownian Dynamics simulations,
      gives insight into the time dependence of the self-diffusion coefficient of an
      interacting colloidal system. As the mean interparticle distance of the matrix is
      of the same order of magnitude as the length of a TMV rod, the rotational motion
      is influenced by the assembly of spheres around a TMV particle. Since FCS is
      sensitive both to translational and rotational motion, whereas FRAP, which probes
      the diffusion at much larger length scales, is only sensitive to the
      translational motion of TMV, the comparison of diffusion coefficients measured
      employing FRAP and FCS can give some insights in the rotational diffusion: the
      experimental data indicate a slowing down of the rotational motion of a TMV rod
      with increasing structural order of the matrix spheres.

PMID- 15473765
TI  - Comment on "Electrostatics in periodic slab geometries. I" [J. Chem. Phys. 117,
      2496 (2002)].

PMID- 15473768
TI  - Tunable resonance hyper-Raman spectroscopy of second-order nonlinear optical
      chromophores.
AB  - Two-photon-resonant hyper-Raman spectra are reported for three "push-pull"
      conjugated organic chromophores bearing -NO(2) acceptor groups, two dipolar and
      one octupolar. The excitation source is an unamplified picosecond mode-locked
      Ti:sapphire laser tunable from 720 to 950 nm. The linear resonance Raman spectra
      of the same molecules are measured using excitation from the laser second
      harmonic. Excitation on resonance with the lowest-lying band in the linear
      absorption spectrum yields nearly identical resonance Raman and resonance hyper
      Raman spectra. However, excitation into a region that appears to contain more
      than one electronic transition gives rise to different intensity patterns in the
      linear and nonlinear spectra, indicating that different transitions contribute
      differently to the one-photon and two-photon oscillator strength. The promise of
      the hyper-Raman technique for examining electronic transitions that are both one-
      and two-photon allowed is discussed.

PMID- 15473769
TI  - Rovibrational-state-selected pulsed field ionization-photoelectron study of
      methyl iodide using two-color infrared-vacuum ultraviolet lasers.
AB  - The preparation of methyl iodide (CH(3)I) in selected rovibrational states
      [nu(7)=1 (C-H stretch); J] by infrared (IR) excitation prior to vacuum
      ultraviolet (VUV) photoionization has greatly simplified the observed pulsed
      field ionization-photoelectron (PFI-PE) spectra, allowing the direct
      determination of the rotational constants B(+)(C(+))=0.254+/-0.003 cm(-1) for
      CH(3)I(+)(X (2)E(3/2);nu(7) (+)) and the ionization energy (76 896.9+/-0.2 cm(
      1)) for CH(3)I(+)(X (2)E(3/2);nu(7) (+)=1,J(+)=3/2)<--CH(3)I(X
      (1)A(1);nu(7)=1,J=0). The IR-VUV-PFI-PE and IR-VUV-photoion measurements also
      provide relative state-to-state (nu(7) (+)=1, J(+)<--nu(7)=1, J) cross sections
      for the photoionization process.

PMID- 15473770
TI  - Evidence of dissociative collision induced diatomic and triatomic hydrogen ion
      formation from hydrocarbon ion interaction with silicon surface.
AB  - A singly charged hydrocarbon ion CH(x) (+) (x=0,1,2,3,4) was extracted from an
      electron bombardment type ion source using methane as the reagent gas and
      irradiated onto the Si(100) surface at glancing angle. Scattered ion spectrometry
      using an electrostatic energy analyzer revealed that H(+), H(2) (+), and H(3) (+)
      ions were clearly formed at the scattering angle of 15 degrees , associated with
      dissociative collisions of hydrocarbon ion species of incidence energy of 1000
      eV. The formation of H(3) (+) was tentatively interpreted as resulting from
      combination of excited atomic hydrogen produced by dissociative collisions of
      CH(4) (+) ions with Si(100) surface.

PMID- 15473771
TI  - Interpreting nonlinear vibrational spectroscopy with the classical mechanical
      analogs of double-sided Feynman diagrams.
AB  - Observables in coherent, multiple-pulse infrared spectroscopy may be computed
      from a vibrational nonlinear response function. This response function is
      conventionally calculated quantum-mechanically, but the challenges in applying
      quantum mechanics to large, anharmonic systems motivate the examination of
      classical mechanical vibrational nonlinear response functions. We present an
      approximate formulation of the classical mechanical third-order vibrational
      response function for an anharmonic solute oscillator interacting with a harmonic
      solvent, which establishes a clear connection between classical and quantum
      mechanical treatments. This formalism permits the identification of the classical
      mechanical analog of the pure dephasing of a quantum mechanical degree of
      freedom, and suggests the construction of classical mechanical analogs of the
      double-sided Feynman diagrams of quantum mechanics, which are widely applied to
      nonlinear spectroscopy. Application of a rotating wave approximation permits the
      analytic extraction of signals obeying particular spatial phase matching
      conditions from a classical-mechanical response function. Calculations of the
      third-order response function for an anharmonic oscillator coupled to a harmonic
      solvent are compared to numerically correct classical mechanical results.

PMID- 15473772
TI  - Excited electronic state calculations by the transcorrelated variational Monte
      Carlo method: application to a helium atom.
AB  - We have implemented the excited electronic state calculations for a helium atom
      by the transcorrelated variational Monte Carlo (TC-VMC) method. In this method,
      Jastrow-Slater-type wave function is efficiently optimized not only for the
      Jastrow factor but also for the Slater determinant. Since the formalism for the
      TC-VMC method is based on the variance minimization, excited states as well as
      the ground state calculations are feasible. It is found that both the first and
      the second excitation energies given by TC-VMC are much closer to the
      experimental data than those given by the variational Monte Carlo method with
      using the Hartree-Fock orbitals. The successful results in the TC-VMC method are
      considered to be due to the nodal optimization of the wave functions.

PMID- 15473773
TI  - Statistical mechanical theory for the structure of steady state systems:
      application to a Lennard-Jones fluid with applied temperature gradient.
AB  - The constrained entropy and probability distribution are given for the structure
      that develops in response to an applied thermodynamic gradient, as occurs in
      driven steady state systems. The theory is linear but is applicable to gradients
      with arbitrary spatial variation. The phase space probability distribution is
      also given, and it is surprisingly simple with a straightforward physical
      interpretation. With it, all of the known methods of equilibrium statistical
      mechanics for inhomogeneous systems may now be applied to determining the
      structure of nonequilibrium steady state systems. The theory is illustrated by
      performing Monte Carlo simulations on a Lennard-Jones fluid with externally
      imposed temperature and chemical potential gradients. The induced energy and
      density moments are obtained, as well as the moment susceptibilities that give
      the rate of change of these with imposed gradient and which also give the
      fluctuations in the moments. It is shown that these moment susceptibilities can
      be written in terms of bulk susceptibilities and also that the Soret coefficient
      can be expressed in terms of them.

PMID- 15473774
TI  - Accurate prediction of heat of formation by combining Hartree-Fock/density
      functional theory calculation with linear regression correction approach.
AB  - A linear regression correction approach has been developed successfully to
      account for the electron correlation energy missing in Hartree-Fock calculation
      and to reduce the calculation errors of density functional theory. The numbers of
      lone-pair electrons, bonding electrons and inner layer electrons in molecules,
      and the number of unpaired electrons in the composing atoms in their ground
      states are chosen to be the most important physical descriptors to determine the
      correlation energy unaccounted by Hartree-Fock method or to improve the results
      calculated by B3LYP density functional theory method. As a demonstration, this
      proposed linear regression correction approach has been applied to evaluate the
      standard heats of formation DeltaH(f) (Theta) of 180 small-sized to medium-sized
      organic molecules at 298.15 K. Upon correction, the mean absolute deviation for
      the 150 molecules in the training set decreases from 351.0 to 4.6 kcal/mol and
      360.9 to 4.6 kcal/mol for HF/6-31G(d) and HF/6-311+G(d,p) methods, respectively.
      For B3LYP method, the mean absolute deviations are reduced from 9.2 and 18.2
      kcal/mol to 2.7 and 2.4 kcal/mol for 6-31G(d) and 6-311+G(d,p) basis sets,
      respectively.

PMID- 15473775
TI  - The role of the reaction force to characterize local specific interactions that
      activate the intramolecular proton transfers in DNA basis.
AB  - MP2/6-311G** and B3LYP/6-311G** studies of the intramolecular proton transfer in
      adenine, cytosine, guanine, and thymine has been performed, with the aim of
      evaluating the role of the reaction force as a global descriptor of the process.
      It turns out that the reaction force profile is quite an interesting tool to
      characterize reaction mechanisms. Indeed, in adenine and cytosine the proton
      transfer is assisted by an increasing electronic delocalization in the adjacent
      ring, whereas in guanine and thymine the attractive electrostatic interaction
      with the acceptor oxygen atom is strong enough to promote the transfer.

PMID- 15473776
TI  - Full configuration interaction calculation of singlet excited states of Be3.
AB  - The full configuration interaction (FCI) study of the singlets vertical spectrum
      of the neutral beryllium trimer has been performed using atomic natural orbitals
      [3s2p1d] basis set. The FCI triangular equilibrium structure of the ground state
      has been used to calculate the FCI vertical excitation energies up to 4.8 eV. The
      FCI vertical ionization potential for the same geometry and basis set amounts to
      7.6292 eV. The FCI dipole and quadrupole transition moments from the ground state
      are reported as well. The FCI electric quadrupole moment of the X (3)A(1) (')
      ground state has been also calculated with the same basis set (Theta(zz)=-2.6461
      a.u., Theta(xx)=Theta(yy)=-1/2Theta(zz)). Twelve of the 19 calculated excited
      singlets are doubly excited states. Most of the states have large
      multiconfigurational character. These results provide benchmark values for
      electronic correlation multireference methods. (4ex6MO)CAS-SDCI values for the
      same energies and properties are also reported.

PMID- 15473777
TI  - Correlated geminal wave function for molecules: an efficient resonating valence
      bond approach.
AB  - We show that a simple correlated wave function, obtained by applying a Jastrow
      correlation term to an antisymmetrized geminal power, based upon singlet pairs
      between electrons, is particularly suited for describing the electronic structure
      of molecules, yielding a large amount of the correlation energy. The remarkable
      feature of this approach is that, in principle, several resonating valence bonds
      can be dealt simultaneously with a single determinant, at a computational cost
      growing with the number of electrons similar to more conventional methods, such
      as Hartree-Fock or density functional theory. Moreover we describe an extension
      of the stochastic reconfiguration method, which was recently introduced for the
      energy minimization of simple atomic wave functions. Within this extension the
      atomic positions can be considered as further variational parameters, which can
      be optimized together with the remaining ones. The method is applied to several
      molecules from Li(2) to benzene by obtaining total energies, bond lengths and
      binding energies comparable with much more demanding multiconfiguration schemes.

PMID- 15473778
TI  - A refined model of the double exchange phenomenon: test on the stretched N2+
      molecule.
AB  - The N2+ molecule is studied at different interatomic distances as a model
      molecule for the double exchange mechanism. The energy spectrum as well as the
      wave functions of the lowest states are analyzed and confronted both with the
      usual model of double exchange and with a recently proposed refined model. It is
      shown that the usual model fails to reproduce the energy spacings while the
      refined model is valid on a large domain of interatomic distances (in the
      magnetic regime). The study of a model molecule on a large domain of interatomic
      distances makes it possible to systematically investigate several regimes
      associated with different energetic state orderings. The perfect agreement
      between the refined model and the computed energies in the whole domain of
      stretched distances shows its applicability to a large number of real compounds.
      Finally, the respective contributions of dynamical and nondynamical correlations
      are analyzed.

PMID- 15473779
TI  - Semiquantal time-dependent Hartree approach to condensed phase chemical dynamics:
      application to the system-bath model.
AB  - A semiquantal analysis of condensed phase chemical dynamics, outlined recently
      for a double-well linearly coupled to dissipative harmonic bath, is formulated in
      detail to clarify its general features as well as the specifics of the linear and
      quadratic coupling cases. The theory may be called a "semiquantal time-dependent
      Hartree (SQTDH)" approach, as it assumes a factorized product of the squeezed
      coherent state wave packets for the variational subspace of the many-dimensional
      time-dependent wave function. Due to this assumption, it straightforwardly
      satisfies the canonicity condition introduced by Marumori et al. is described by
      a set of Hamilton equations of motion in an extended phase space that includes
      auxiliary coordinates representing the wave packet widths. The potential in the
      extended phase space provides a pictorial understanding of the quantum effects
      affected due to the bath coupling, e.g., suppression of the wave packet spreading
      in terms of the potential wall developing along the auxiliary coordinates. The
      idea is illustrated by prototypical models of quartic double-well and cubic
      metastable potentials linearly and quadratically coupled to the bath. Further
      applications and extensions, where the SQTDH method will offer a practical
      approach for introducing quantum effects into realistic molecular dynamics
      simulations, are also discussed.

PMID- 15473780
TI  - Interpretation of Hund's multiplicity rule for the carbon atom.
AB  - Hund's multiplicity rule is investigated for the carbon atom using quantum Monte
      Carlo methods. Our calculations give an accurate account of electronic
      correlation and obey the virial theorem to high accuracy. This allows us to
      obtain accurate values for each of the energy terms and therefore to give a
      convincing explanation of the mechanism by which Hund's rule operates in carbon.
      We find that the energy gain in the triplet with respect to the singlet state is
      due to the greater electron-nucleus attraction in the higher spin state, in
      accordance with Hartree-Fock calculations and studies including correlation. The
      method used here can easily be extended to heavier atoms.

PMID- 15473781
TI  - New Rydberg-Rydberg transitions in N2. Identification of the d3 1Sigmag+ state.
AB  - Use of a special Penning-ionization source allowed Fourier-transform recording of
      two previously nonobserved IR emission bands spectra at 5480 and 7630 cm(-1)
      arising from neutral N(2). The first of these bands is the c(4) (') (1)Sigma(u)
      (+)-a(") (1)Sigma(g) (+) (0,0) transition, both states involved being previously
      known by direct vacuum (UV) absorption spectroscopy. The second band corresponds
      to a d(3) (1)Sigma(g) (+)-c(4) (') (1)Sigma(u) (+) (0,0) transition, in which the
      upper level belongs to an up to now unidentified Rydberg state. Both the upper
      and lower levels are perturbed by neighboring valence state levels.

PMID- 15473782
TI  - Dissociation energies of six NO2 isotopologues by laser induced fluorescence
      spectroscopy and zero point energy of some triatomic molecules.
AB  - We have measured the rotationless photodissociation threshold of six
      isotopologues of NO2 containing 14N, 15N, 16O, and 18O isotopes using laser
      induced fluorescence detection and jet cooled NO2 (to avoid rotational
      congestion). For each isotopologue, the spectrum is very dense below the
      dissociation energy while fluorescence disappears abruptly above it. The six
      dissociation energies ranged from 25 128.56 cm(-1) for 14N16O2 to 25 171.80 cm(
      1) for 15N18O2. The zero point energy for the NO2 isotopologues was determined
      from experimental vibrational energies, application of the Dunham expansion, and
      from canonical perturbation theory using several potential energy surfaces. Using
      the experimentally determined dissociation energies and the calculated zero point
      energies of the parent NO2 isotopologue and of the NO product(s) we determined
      that there is a common De = 26 051.17+/-0.70 cm(-1) using the Born-Oppenheimer
      approximation. The canonical perturbation theory was then used to calculate the
      zero point energy of all stable isotopologues of SO2, CO2, and O3, which are
      compared with previous determinations.

PMID- 15473783
TI  - Dynamics of Rydberg electron transfer to CH3CN: velocity dependent studies.
AB  - The dynamics of free-ion production through electron transfer in K(np)/CH3CN
      collisions are examined through measurements using velocity-selected Rydberg
      atoms. The data show that Rydberg electron transfer leads to the creation of two
      groups of dipole-bound CH3CN- ions, one long lived (tau>85 micros), the other
      short lived (tau<1 micros). The velocity dependences associated with the
      production of both groups of ions are similar, the ion formation rate decreasing
      markedly with decreasing Rydberg atom velocity, principally as a consequence of
      postattachment electrostatic interactions between the product ions. The results
      are in reasonable accord with the predictions of a Monte Carlo collision model
      that considers the effect of crossings between the diabatic potential curves for
      the covalent K(np)/CH3CN system and the K+/CH3CN- ion pair. This model also
      accounts for the relatively small reaction rate constants, approximately 0.5-1.0
      x 1.0(-8) cm(3) s(-1), associated with the formation of long-lived CH3CN- ions.
      No velocity dependence in the lifetime of the CH3CN- ions is observed.

PMID- 15473784
TI  - Fragmentation and conformation study of ephedrine by low- and high-resolution
      mass selective UV spectroscopy.
AB  - The neurotransmitter molecule, ephedrine, has been studied by mass-selective low-
      and high-resolution UV resonance enhanced two-photon ionization spectroscopy.
      Under all experimental conditions we observed an efficient fragmentation upon
      ionization. The detected vibronic peaks in the spectrum are classified according
      to the efficiency of the fragmentation, which leads to the conclusion that there
      exist three different species in the molecular beam: ephedrine-water cluster and
      two distinct conformers. The two-color two-photon ionization experiment with a
      decreased energy of the second photon leads to an upper limit of 8.3 eV for the
      ionization energy of ephedrine. The high-resolution (70 MHz) spectrum of the
      strongest vibronic peak in the spectrum measured at the fragment (m/z=58) mass
      channel displays a pronounced and rich rotational structure. Its analysis by the
      use of a specially designed computer-aided rotational fit process yields accurate
      rotational constants for the S(0) and S(1) states and the transition moment
      ratio, providing information on the respective conformational structure.

PMID- 15473785
TI  - The dynamics of the Cl+n-C4H10-->HCl (v',j') + C4H9 reaction at 0.32 eV.
AB  - Rotational state resolved center-of-mass angular scattering and kinetic energy
      release distributions have been determined for the HCl (v' = 0, j' = 0-6)
      products of the reaction of chlorine with n-butane using the photon-initiated
      reaction technique, coupled with velocity-map ion imaging. The angular and
      kinetic energy release distributions derived from the ion images are very similar
      to those obtained previously for the Cl plus ethane reaction. The angular
      distributions are found to shift from forward scattering to more isotropic
      scattering with increasing HCl rotational excitation. The kinetic energy release
      distributions indicate that around 30% of the available energy is channeled into
      internal excitation of the butyl radical products. The data analysis also
      suggests that H-atom abstraction takes place from both primary and secondary
      carbon atom sites, with the primary site producing rotationally cold, forward
      scattered HCl (v' = 0) products, and the secondary site yielding more
      isotropically scattered HCl (v' = 0) possessing higher rotational excitation. The
      mechanisms leading to these two product channels are discussed in the light of
      the present findings, and in comparison with studies of other Cl plus alkane
      reactions.

PMID- 15473786
TI  - A theoretical study of the staggered and eclipsed forms of the dinuclear complex
      Mn Re(CO)10.
AB  - Two possible conformers of the dinuclear complex Mn Re(CO)10, each of C(4v)
      symmetry, with eclipsed and staggered conformations, have been analyzed
      theoretically. Using both the B3LYP and BP86 density functionals we find that the
      staggered form is lower in energy. A determination of the B3LYP potential energy
      surface as a function of the Mn-Re distance is presented for both conformers. The
      computed bond lengths, bond angles, and rotational constant for the staggered
      conformation compare favorably with the results from microwave experiments. The
      harmonic frequencies for the staggered structure have been determined using
      several basis sets, with both analytical and finite difference methods. These
      unscaled vibrational frequencies, together with their intensities for both
      infrared and Raman activity, are used to assign the three most intense
      experimental IR and Raman bands, and in particular, the nu(CO) region. The lowest
      A(2) vibration was calculated to occur at 41 cm(-1) in the staggered conformer;
      this frequency becomes imaginary in the (saddle point) eclipsed form. Several
      fundamentals remain to be observed experimentally.

PMID- 15473787
TI  - Low-lying electronic states of the Ti2 dimer: electronic absorption spectroscopy
      in rare gas matrices in concert with quantum chemical calculations.
AB  - Absorption spectra were measured for Ti2 in Ne and Ar matrices. The spectra give
      evidence for several electronic transitions in the region between 4000 and 10 000
      cm(-1) and provide important information about some excited electronic states of
      Ti2 in proximity to the ground state. The vibrational fine structure measured for
      these transitions allowed to calculate the force constants and the anharmonicity
      of the potential energy curves of the excited states, and to estimate changes in
      the internuclear Ti-Ti distances relative to the electronic ground state. The
      quantum chemical studies confirm the previously suggested (3)Delta(g) state as
      the ground state of Ti2. The equilibrium bond distance is calculated to be 195.4
      pm. The calculated harmonic frequency of 432 cm(-1) is in good agreement with the
      experimental value of 407.0 cm(-1). With the aid of the calculations it was
      possible to assign the experimentally observed transitions in the region between
      4000 and 10 000 cm(-1) to the 1 (3)Pi(u)<--(3)Delta(g), 1 (3)Phi(u)<-
      (3)Delta(g), 2 (3)Pi(u)<--(3)Delta(g), 2 (3)Phi(u)<--(3)Delta(g), and
      (3)Delta(u)<--(3)Delta(g) excitations (in the order of increasing energy). The
      calculated relative energies and harmonic frequencies are in pleasing agreement
      with the experimentally obtained values, with deviations of less than 5% and 2%,
      respectively. The bond distances estimated on the basis of the experimental
      spectra tally satisfactorily with the predictions of our calculations.

PMID- 15473788
TI  - Interaction of lead atom with atmospheric hydroxyl radical. An ab initio and
      density functional theory study of the resulting complexes PbOH and HPbO.
AB  - The two potential hypersurfaces 2A' (ground state) and 2A" (excited state) have
      been studied through ab initio and density functional theory (DFT) methods for
      the Pb(OH) complex. Two processes have been identified. The first one concerns
      the hydrogen inversion process in the coordination of PbOH and the second one the
      isomerization of PbOH into HPbO. Eight stationary points have been found; four of
      them correspond to the stable structures with symmetries PbOH(2A'), PbOH(2A"),
      HPbO(2A'), and HPbO(2Pi), and four correspond to transition states [TS] with the
      symmetries 2Pi, 2A', 2Sigma+, and 2A". The hydrogen inversion process in PbOH
      exhibits the so-called Renner-Teller effect with a rather low barrier, whereas
      the isomerization process PbOH-->HPbO exhibits a rather high barrier. The
      energetic, structural, spectroscopy, and thermodynamics results obtained at
      various levels through, e.g., DFT with BLYP, B3LYP exchange-correlation
      functionals, coupled clusters methods, namely CCSD (single and double
      excitations) and CCSD(T) (with triple excitations, by perturbation) are presented
      for the whole sets of the stationary points and their dissociation products. The
      relativistic effects, as well as spin-orbit interaction, taken into account in
      the case of the BLYP exchange-correlation functional, have been estimated and
      discussed in order to measure their importance in the case of system including
      heavy metals such as Pb. Reactions of lead (Pb) with oxidizing atmospheric
      molecules (OH, HO2, O2, and O3) have been studied at various levels of
      approximation in order to study the possible existence of PbOH in the atmosphere.

PMID- 15473789
TI  - Measurement of Br photofragment orientation and alignment from HBr
      photodissociation: production of highly spin-polarized hydrogen atoms.
AB  - The orientation and alignment of the (2)P(3/2) and (2)P(1/2) Br photofragments
      from the photodissociation of HBr is measured at 193 nm in terms of a(q) ((k))(p)
      parameters, using slice imaging. The A (1)Pi state is excited almost exclusively,
      and the measured a(q) ((k))(p) parameters and the spin-orbit branching ratio show
      that the dissociation proceeds predominantly via nonadiabatic transitions to the
      a (3)Pi and 1 (3)Sigma(+) states. Conservation of angular momentum shows that the
      electrons of the nascent H atom cofragments (recoiling parallel to the photolysis
      polarization) are highly spin polarized: about 100% for the Br((2)P(1/2))
      channel, and 86% for the Br((2)P(3/2)) channel. A similar analysis is
      demonstrated for the photodissociation of HCl.

PMID- 15473790
TI  - Structural analysis of porphyrin molecular squares using molecular mechanics and
      density-functional methods.
AB  - "Molecular squares" formed from Re(CO)(3)Cl corners and porphyrin sides have
      potential applications as hosts for catalytic sites and as building blocks for
      membranes. In these materials, knowledge of the conformations of the squares is
      important. Molecular-mechanics (MM) and density-functional (DF) calculations have
      been used iteratively in this work to find the minimum-energy configurations of
      several porphyrin molecular squares. MM predicts that the steric and torsional
      interactions at connecting junctures of the square framework determine the
      overall geometry. Torsional degrees of freedom around these junctures were
      therefore analyzed using DF methods, giving further insight and helping choose
      among MM force-field options. Single-point DF calculations on the entire squares
      showed that the energy and conformation of the entire square could be reliably
      obtained by performing DF calculations on the critical elements of the square and
      then piecing them together. This "piecewise" strategy allows for both the major
      torsional motions and the most important local relaxations of large
      supramolecular species such as molecular squares.

PMID- 15473791
TI  - An optical-optical double resonance experiment in LiH molecules: lifetime
      measurements in the C state.
AB  - An optical-optical double resonance sub-Doppler experiment is used to measure
      short nonradiative lifetimes in the C (1)Sigma(+) state of LiH. These lifetimes
      are expected to result from the strong electronic interaction between the C
      (1)Sigma(+) state and the continuum of the A (1)Sigma(+) state and to vary with
      the vibrational quantum number, from nanoseconds to milliseconds. The
      experimental setup combines a molecular beam of LiH, a first cw laser beam locked
      to a given A-X absorption line, and a second cw laser beam scanned over C-A
      absorption profiles. Analysis of these absorption profiles in terms of Voigt
      profiles shows that their Lorentzian components significantly vary with the
      vibrational quantum numbers of the C state. Nonradiative decay rates deduced this
      way are systematically larger than the calculated ones but their variations are
      similar. Coherent saturation effects cannot be invoked to explain this
      discrepancy.

PMID- 15473792
TI  - Structural and electronic properties of small beryllium clusters: a theoretical
      study.
AB  - Geometric structures and electronic properties of small beryllium clusters
      (Be(n), 2< or = n< or =9) are investigated within the gradient-corrected density
      functional theory. The computations are performed with the Becke exchange and
      Perdew-Wang correlation functionals. Both low and high multiplicity states are
      considered. A predominance of higher multiplicity states among the low-energy
      isomers of the larger clusters is found. An analysis of the variations in the
      structural and electronic properties with cluster size is presented, and the
      results are compared with those of earlier studies.

PMID- 15473793
TI  - Mechanisms and dynamics of the metastable decay in Ar2+.
AB  - A detailed experimental as well as theoretical investigation of the properties of
      the metastable dissociation Ar2+ --> Ar+ + Ar is presented. The mass-analyzed ion
      kinetic energy (MIKE) scan technique has been performed using a three sector
      field mass spectrometer. The possible mechanisms of the metastability of Ar2+
      have been examined and the observed decay process is assigned to the II(1/2)(u)-
      >I(1/2)(g) bound to continuum radiative transition, in agreement with earlier
      work. The calculation of the theoretical shape of the kinetic energy release
      distribution of fragment ions allowed us to construct the theoretical MIKE peak
      and compare it with the raw experimental data. The accuracy of various sets of
      potential energy curves for Ar2+ is discussed, as well as the way of production
      of the metastable Ar2+[II(1/2)(u)] electronic state by electron impact. Excellent
      agreement between the experimental data and theoretical model has been observed.

PMID- 15473794
TI  - Experimental and theoretical study of the infrared spectra of BrHI- and BrDI-.
AB  - Gas phase vibrational spectra of BrHI- and BrDI- have been measured from 6 to 17
      microm (590-1666 cm(-1)) using tunable infrared radiation from the free electron
      laser for infrared experiments in order to characterize the strong hydrogen bond
      in these species. BrHI-.Ar and BrDI-.Ar complexes were produced and mass
      selected, and the depletion of their signal due to vibrational predissociation
      was monitored as a function of photon energy. Additionally, BrHI- and BrDI- were
      dissociated into HBr (DBr) and I- via resonant infrared multiphoton dissociation.
      The spectra show numerous transitions, which had not been observed by previous
      matrix studies. New ab initio calculations of the potential-energy surface and
      the dipole moment are presented and are used in variational ro-vibrational
      calculations to assign the spectral features. These calculations highlight the
      importance of basis set in the simulation of heavy atoms such as iodine. Further,
      they demonstrate extensive mode mixing between the bend and the H-atom stretch
      modes in BrHI- and BrDI- due to Fermi resonances. These interactions result in
      major deviations from simple harmonic estimates of the vibrational energies. As a
      result of this new analysis, previous matrix-isolation spectra assignments are
      reevaluated.

PMID- 15473795
TI  - Study of the stabilization energies of halide-water clusters: an application of
      first-principles interaction potentials based on a polarizable and flexible
      model.
AB  - The aim of this work is to compute the stabilization energy E(stab)(n) of
      [X(H(2)O)(n)](-) (X identical with F, Br, and I for n=1-60) clusters from Monte
      Carlo simulations using first-principles ab initio potentials. Stabilization
      energy of [X(H(2)O)(n)](-) clusters is defined as the difference between the
      vertical photodeachment energy of the cluster and the electron affinity of the
      isolated halide. On one hand, a study about the relation between cluster
      structure and the E(stab)(n) value, as well as the dependence of the latter with
      temperature is performed, on the other hand, a test on the reliability of our
      recently developed first-principles halide ion-water interaction potentials is
      carried out. Two different approximations were applied: (1) the Koopmans' theorem
      and (2) calculation of the difference between the interaction energy of
      [X(H(2)O)(n)](-) and [X(H(2)O)(n)] clusters using the same ab initio interaction
      potentials. The developed methodology allows for using the same interaction
      potentials in the case of the ionic and neutral clusters with the proviso that
      the charge of the halide anion was switched off in the latter. That is, no
      specific parametrization of the interaction potentials to fit the magnitude under
      study was done. The good agreement between our predicted E(stab)(n) and
      experimental data allows us to validate the first-principles interaction
      potentials developed elsewhere and used in this study, and supports the fact that
      this magnitude is mainly determined by electrostatic factors, which can be
      described by our interaction potentials. No relation between the value of
      E(stab)(n) and the structure of clusters has been found. The diversity of
      E(stab)(n) values found for different clusters with similar interaction energy
      indicates the need for statistical information to properly estimate the
      stabilization energy of the halide anions. The effect of temperature in the
      prediction of the E(stab)(n) is not significant as long as it was high enough to
      avoid cluster trapping into local equilibrium configurations which guarantees an
      appropriate sampling of the configurational space. Parallel tempering method was
      applied in particular cases to guarantee satisfactory sampling of clusters at low
      temperature.

PMID- 15473796
TI  - Drift of rigidly rotating spirals under periodic and noisy illuminations.
AB  - Under the weak deformation approximation, the motion of rigidly rotating spirals
      induced by periodic and noisy illuminations are investigated analytically. We
      derive an approximate but explicit formula of the spiral drift velocity directly
      from the original reaction-diffusion equation. With this formula we are able to
      explain the main features in the periodic and noisy illuminations induced spiral
      drift problems. Numerical computations of the Oregonator model are carried out as
      well, and they agree with the main qualitative conclusions of our analytical
      results.

PMID- 15473798
TI  - Raman spectra of ionic liquids: a simulation study of LaCl3 and its mixtures with
      alkali chlorides.
AB  - Theoretical Raman spectra of the elpasolite-structured crystal Cs2NaLaCl6 and of
      molten mixtures of LaCl6 with NaCl and CsCl have been obtained from computer
      simulations in order to examine how the Raman spectra reflect the coordination
      structure around the La3+ ions. This system is a model for many other trivalent
      metal halides and for examining how the network structure of the pure melts is
      broken down by the addition of alkali halides with different structure-breaking
      powers. The results suggest a way of reconciling the conclusions of Raman studies
      about the structures of the melts with those of neutron and x-ray-diffraction
      studies, which have already been examined with the same simulation methods. The
      Raman spectra, both polarized and depolarized, are calculated from a model for
      the dependence of the polarizability of the system on the ionic coordinates which
      was inspired by electronic structure calculations of the polarizabilities of ions
      in a condensed phase environment. Some results on the lifetimes of the
      coordination complexes responsible for the appearance of the discrete Raman bands
      are discussed.

PMID- 15473797
TI  - Multidimensional infrared spectroscopy of the N-H bond motions in formamide.
AB  - The heterodyned two-dimensional (2D) IR spectra and equilibrium dynamics of the N
      H stretching motion of DCONHD in deuterated formamide, DCOND(2), were studied
      with 80 fs pulses at 3 microm. The time evolution of the heterodyned 2D IR
      spectra, pump-probe spectra, and photon echo peak shift demonstrate that
      interstate dynamics is occurring by relaxation of the original N-H excitation.
      The N-H vibrational frequency correlation function can be expressed as a sum of
      three exponentials with correlation times 0.24 ps, 0.8 ps, and 11 ps. The
      intermediate component is attributed to motions of the N-Hcdots, three dots,
      centeredO unit involving only slight angular variations of the N-H bond. The slow
      component is attributed to the structure breaking and making. The anisotropy
      decay confirmed that the significant angular N-H bond motion occurs on the 11 ps
      time scale. The fast component, which is the least well determined, might
      correspond to the modulation of the H-bond distance without angular motion. The
      correlation coefficient between the pumped and relaxed state distributions was
      +0.51, implying that the excited state phase memory is only slightly diminished
      by the relaxation of the N-H excitation. The relaxed modes are concluded to be
      local to the driven N-H mode.

PMID- 15473799
TI  - Hydrophobic effect in the pressure-temperature plane.
AB  - The free energy of the hydrophobic hydration and the strength of the solvent
      mediated attraction between hydrophobic solute molecules are calculated in the
      pressure-temperature plane. This is done in the framework of an exactly soluble
      model that is an extension of the lattice model proposed by Kolomeisky and Widom.
      The model takes into account both the mechanism of the hydrophobic effect
      dominant at low temperatures and the opposite mechanism of solvation appearing at
      high temperatures and has the pressure as a second thermodynamic variable. With
      this model, two boundaries are identified in the pressure-temperature plane: the
      first one within which the solubility, or the Ostwald absorption coefficient,
      decreases with increasing temperature at fixed pressure and the second one within
      which the strength of solvent-mediated attraction increases with increasing
      temperature. The two are nearly linear and parallel to each other, and the second
      boundary lies in the low-temperature and low-pressure side of the first boundary.
      It is found that a single, near-linear relation between the hydration free energy
      and the strength of the hydrophobic attraction holds over the entire area within
      the second boundary in the pressure-temperature plane.

PMID- 15473800
TI  - NMR polarization echoes in a nematic liquid crystal.
AB  - We have modified the polarization echo (PE) sequence through the incorporation of
      Lee-Goldburg cross polarization steps to quench the 1H-1H dipolar dynamics. In
      this way, the 13C becomes an ideal local probe to inject and detect polarization
      in the proton system. This improvement made possible the observation of the local
      polarization P(00)(t) and polarization echoes in the interphenyl proton of the
      liquid crystal N-(4-methoxybenzylidene)-4-butylaniline. The decay of P(00)(t) was
      well fitted to an exponential law with a characteristic time tau(C) approximately
      310 micros. The hierarchy of the intramolecular dipolar couplings determines a
      dynamical bottleneck that justifies the use of the Fermi Golden Rule to obtain a
      spectral density consistent with the structural parameters. The time evolution of
      P(00)(t) was reversed by the PE sequence generating echoes at the time expected
      by the scaling of the dipolar Hamiltonian. This indicates that the reversible 1H
      1H dipolar interaction is the main contribution to the local polarization
      decrease and that the exponential decay for P(00)(t) does not imply
      irreversibility. The attenuation of the echoes follows a Gaussian law with a
      characteristic time tau(phi) approximately 527 micros. The shape and magnitude of
      the characteristic time of the PE decay suggest that it is dominated by the
      unperturbed homonuclear dipolar Hamiltonian. This means that tau(phi) is an
      intrinsic property of the dipolar coupled network and not of other degrees of
      freedom. In this case, one cannot unambiguously identify the mechanism that
      produces the decoherence of the dipolar order. This is because even weak
      interactions are able to break the fragile multiple coherences originated on the
      dipolar evolution, hindering its reversal. Other schemes to investigate these
      underlying mechanisms are proposed.

PMID- 15473801
TI  - Pressure induced phase transitions in hydroquinone.
AB  - High pressure behavior of alpha-hydroquinone (1,4-dihydroxybenzene) has been
      studied using Raman spectroscopy up to pressures of 19 GPa. Evolution of Raman
      spectra suggests two transitions around 3.3 and 12.0 GPa. The first transition
      appears to be associated with the lowering of crystal symmetry. Above 12.0 GPa,
      Raman bands in the internal modes region exhibit continuous broadening suggesting
      that the system is progressively evolving into a disordered state. This disorder
      is understood as arising due to distortion of the hydrogen-bonded cage across the
      second transition around 12 GPa.

PMID- 15473802
TI  - Computation of the properties of liquid neon, methane, and gas helium at low
      temperature by the Feynman-Hibbs approach.
AB  - The properties of liquid methane, liquid neon, and gas helium are calculated at
      low temperatures over a large range of pressure from the classical molecular
      dynamics simulations. The molecular interactions are represented by the Lennard
      Jones pair potentials supplemented by quantum corrections following the Feynman
      Hibbs approach. The equations of state, diffusion, and shear viscosity
      coefficients are determined for neon at 45 K, helium at 80 K, and methane at 110
      K. A comparison is made with the existing experimental data and for
      thermodynamical quantities, with results computed from quantum numerical
      simulations when they are available. The theoretical variation of the viscosity
      coefficient with pressure is in good agreement with the experimental data when
      the quantum corrections are taken into account, thus reducing considerably the
      60% discrepancy between the simulations and experiments in the absence of these
      corrections.

PMID- 15473803
TI  - Dielectric study of the alpha and beta processes in supercooled ethylene glycol
      oligomer-water mixtures.
AB  - Broadband dielectric measurements for 65 wt % ethylene glycol oligomer (EGO)
      water mixtures with one to six repeat units of EGO molecules were performed in
      the frequency range of 10 microHz-10 GHz and the temperature range of 128-298 K.
      In the case of the water-EGO mixtures with one and two repeat units of the EGO
      molecule (small EGO), the shape of the dielectric loss peak of the primary
      process is asymmetrical about the logarithm of the frequency of maximum loss
      above the crossover temperature, T(C). The asymmetric process continues to the
      alpha process at a low frequency, and an additional beta process appears in the
      frequency range higher than that of the alpha process below T(C). In contrast,
      the water-EGO mixtures with three or more repeat units of the EGO molecule (large
      EGO) show a broad and symmetrical loss peak of the primary process above T(C).
      The symmetric process continues to the beta process, and an additional alpha
      process appears in the frequency range lower than that of the beta process below
      T(C). These different scenarios of the alpha-beta separation related to the shape
      of the loss peak above T(C) are a result of the difference in the cooperative
      motion of water and solute molecules. The solute and water molecules move
      cooperatively in the small EGO-water mixtures above T(C), and this cooperative
      motion leads to the asymmetric loss peak above T(C) and the alpha process below
      T(C). For the large EGO-water mixtures, the spatially restricted motion of water
      confined by solute molecules leads to the symmetric loss peak above T(C) and the
      beta process below T(C).

PMID- 15473804
TI  - Relaxation time scales in collective dynamics of liquid alkali metals.
AB  - In this paper the investigation of the dynamical processes of liquid alkali
      metals is executed by analyzing the time scales of relaxation processes in
      liquids. The obtained theoretical dynamic structure factor S(k,omega) for the
      case of liquid lithium is found to be in excellent agreement with the recently
      received inelastic x-ray scattering data. The comparison and interrelation with
      other theories are given here. Finally, an important part of this paper is the
      confirmation of the scale uniformity of the dynamic processes in liquid alkali
      metals predicted by some previous molecular dynamic simulation studies.

PMID- 15473805
TI  - On the Adam-Gibbs-Kirkpatrick-Thirumalai-Wolynes scenario for the viscosity
      increase in glasses.
AB  - We reformulate the interpretation of the mean-field glass transition scenario for
      finite dimensional systems, proposed by Kirkpatrick, Thirumalai, and Wolynes
      (KTW). This allows us to establish clearly a temperature dependent length xi( *)
      above which the mean-field glass transition picture has to be modified. We argue
      in favor of the mosaic state introduced by KTW, which leads to the Adam-Gibbs
      relation between the viscosity and configurational entropy of glass forming
      liquids. Our argument is a mixture of thermodynamics and kinetics, partly
      inspired by the random energy model: small clusters of particles are
      thermodynamically frozen in low energy states, whereas large clusters are
      kinetically frozen by large activation energies. The relevant relaxation time is
      that of the smallest "liquid" clusters. Some physical consequences are discussed.

PMID- 15473806
TI  - Equation of state for hard-sphere fluid in restricted geometry.
AB  - Many practical applications require the knowledge of the equation of state of
      fluids in restricted geometry. We study a hard-sphere fluid at equilibrium in a
      narrow cylindrical pore with hard walls for pore radii R<((square root 3)+2)/4
      (in units of the hard sphere diameter). In this case each particle can interact
      only with its nearest neighbors, which makes possible the use of analytical
      methods to study the thermodynamics of the system. Using a transfer operator
      formalism and expanding in low- and high-pressure regions, we can obtain a simple
      analytical equation of state for almost all ranges of pressure. The results agree
      with Monte Carlo simulations. Additionally, it is shown that a convenient
      analytical representation can be chosen to accurately describe the equation of
      state within the error of the Monte Carlo simulation.

PMID- 15473807
TI  - On the performance of molecular polarization methods. I. Water and carbon
      tetrachloride close to a point charge.
AB  - The three main methods to implement molecular polarization (point dipoles,
      fluctuating charges, and shell model) are tested against high level ab initio
      calculations for a molecule (water, carbon tetrachloride) close to a point charge
      (at the distance of a lithium or magnesium ion). The goal is to check whether an
      approximation (linear polarization) strictly valid at large intermolecular
      distances is sufficiently accurate for liquid state molecular dynamics
      simulations, where strong polarization effects are to be expected at short
      separations. The monitored observable is the molecular dipole moment as a
      function of the charge-molecule distance for selected molecular orientations.
      Analytic formulas are derived for the components of the molecular polarization
      tensor, facilitating the optimization of the performance for each polarization
      method as a function of its underlying parameters. Overall, the methods studied
      provide a remarkably good representation of the induced dipole, with no
      divergences appearing even at the shortest distances. For water close to a
      monovalent point charge the point dipole model, implemented with one or three
      dipoles, accurately reproduces the water dipole moment at all distances.
      Deficiencies appear as the molecular polarizability and/or charge increase:
      basically, the ab initio induced moments grow faster at intermediate distances
      than the linear increase characteristic of the phenomenological polarization
      methods, suggesting that nonlinear effects (hyperpolarizability) cannot be
      neglected in these cases. Regarding the capabilities of each method, the point
      dipole method is the one that performs best overall, with the shell model
      achieving acceptable results in most instances. The fluctuating charge method
      shows some noticeable limitations for implementations of comparable complexity
      (in terms of the number of sites required).

PMID- 15473808
TI  - Physical properties of sulfur near the polymerization transition.
AB  - Acoustical measurements, electron spin resonance, and Raman spectroscopy have
      been employed to probe sulfur over the temperature range 80-180 degrees C, which
      includes the polymerization transition and the supercooled liquid state.
      Acoustical properties (sound velocity, absorption, and impedance) have been
      studied with both longitudinal and transverse waves at frequencies between 500
      kHz and 22 MHz. The results confirm that polymeric sulfur is a solution of long
      chain molecules in monomeric solvent, and that the polymerization transition is
      not a second-order phase transition, as was proposed theoretically. Sulfur is a
      viscous liquid, but not viscoelastic, both below and above the polymerization
      transition temperature. It is shown that the classical Navier-Stokes theory is
      not applicable to the sound absorption in liquid sulfur in the highly viscous
      state.

PMID- 15473809
TI  - On asymmetry between superheating and supercooling in solid-liquid transitions:
      Landau models.
AB  - We investigated the asymmetry between superheating and supercooling in solid
      liquid transitions using two Landau-type models for the first-order phase
      transitions, the Landau-Devonshire and Landau-de Gennes models. The Landau models
      reproduced the asymmetric behavior described by the classical nucleation theory.

PMID- 15473810
TI  - Theoretical investigation of the linear and second-order nonlinear
      susceptibilities of the 3-methyl-4-nitropyridine-1-oxyde (POM) crystal.
AB  - The linear and nonlinear optical properties of the 3-methyl-4-nitropyridine-1
      oxyde (POM) crystal have been evaluated using semiempirical quantum chemistry
      techniques. The scheme includes (i) the evaluation of the polarizability and
      first hyperpolarizability of increasingly large one-dimensional, two-dimensional,
      and three-dimensional clusters of POM, (ii) the use of the time-dependent Hartree
      Fock approach to determine the static and dynamic responses in combination with
      semiempirical Austin model 1 Hamiltonian, (iii) the assessment, for the POM
      monomer and dimer, of the electron correlation effects using second-order Moller
      Plesset perturbation theory with several basis sets containing polarization and
      diffuse functions, (iv) the assessment of the validity of the multiplicative
      scheme and its application to get effective polarizability and first
      hyperpolarizability of the POM unit cell in the crystal, (v) the use of a sum
      over-states approach to attribute the first hyperpolarizability to a dominant
      charge-transfer excited state, and (vi) comparison with experimental data as well
      as with calculated values obtained using the oriented gas approximation.

PMID- 15473811
TI  - The force generated by biological membranes on a polymer rod and its response:
      statics and dynamics.
AB  - We propose a theory for the force exerted by a fluctuating membrane on a polymer
      rod tip. Using statistical mechanical methods, the expression for the generated
      force is written in terms of the distance of the rod tip from the membrane
      "frame." We apply the theory in calculating the stall force and membrane
      displacement required to cease the growth of a growing fiber induced by membrane
      fluctuations, as well as the membrane force and membrane displacement required
      for rod/fiber buckling. We also consider the dynamics of a growing fiber tip
      under the influence of a fluctuation-induced membrane force. We discuss the
      importance of our results in various biological contexts. Finally, we present a
      method to simultaneously extract both the rigidity of the semiflexible rod and
      the force applied by, e.g., the membrane from the measurements of the bending
      fluctuations of the rod. Such a measurement of the force would give information
      about the thermodynamics of the rod polymerization that involves the usual
      Brownian ratchet mechanism.

PMID- 15473812
TI  - Compressed CO2-enhanced solubilization of 1-butyl-3-methylimidazolium
      tetrafluoroborate in reverse micelles of Triton X-100.
AB  - We carried out the first study about the effect of a compressed gas on the
      properties of reverse micellar solutions with ionic liquid (IL) polar cores. And
      the properties of compressed CO2/cyclohexane/1-butyl-3-methylimidazolium
      tetrafluoroborate ([bmim][BF4])/Triton X-100 (TX-100) system were investigated at
      288.2, 293.2, 298.2, 308.2 K and different pressures by using phase behavior
      measurement, small-angle x-ray scattering, and UV-Vis techniques. The
      concentration of the surfactant in the solution was 0.3 mol/l (M). It was found
      that compressed CO2 could enhance solubilization of the IL in the reverse
      micelles considerably at suitable pressures, and formation of the reverse
      micelles could be controlled easily by pressure. Increase of CO2 pressure
      resulted in decrease of the micellar sizes at fixed [bmim][BF4]-to-surfactant
      molar ratios (w), and the size of the reverse micelles increased with the
      increase of w values. The polarity of the IL cores increased continuously with
      increasing w value.

PMID- 15473813
TI  - Molecular dynamics simulation on devitrification: isothermal devitrification and
      thermodynamics of PbF2 glasses.
AB  - The vitrification and devitrification features of lead fluoride are investigated
      by means of molecular dynamic simulations. The influence of heating rate on the
      devitrification temperature as well as the dependence of the glass properties on
      its thermal history, i.e., the cooling rate employed, is identified. As expected,
      different glasses are obtained when the cooling rates differ. Diffusion
      coefficient analysis during heating of glass and crystal, indicates that the
      presence of defects on the glassy matrix favors the transition processes from the
      ionic to a superionic state, with high mobility of fluorine atoms, responsible
      for the high anionic conduction of lead fluoride. Nonisothermal and isothermal
      devitrification processes are simulated in glasses obtained at different cooling
      rates and structural organizations occurring during the heat treatments are
      clearly observed. When a fast cooling rate is employed during the glass
      formation, the devitrification of a single crystal (limited by the cell
      dimensions) is observed, while the glass obtained with slower cooling rate,
      allowing relaxations and organization of various regions on the glass bulk during
      the cooling process, devitrifies in more than one crystalline plane.

PMID- 15473814
TI  - Water-soluble silica-overcoated CdS:Mn/ZnS semiconductor quantum dots.
AB  - Highly luminescent and photostable CdS:Mn/ZnS core/shell quantum dots are not
      water soluble because of their hydrophobicity. To create water-soluble quantum
      dots by an appropriate surface functionalization, CdS:Mn/ZnS quantum dots
      synthesized in a water-in-oil (W/O) microemulsion system (reverse micelles) were
      consecutively overcoated with a very thin silica layer ( approximately 2.5 nm
      thick) within the same reverse micellar system. The water droplet serves as a
      nanosized reactor for the controlled hydrolysis and condensation of a silica
      precursor, tetraethyl orthosilicate (TEOS), using an ammonium hydroxide (NH4OH)
      catalyst. Structural characterizations with transmission electron microscopy
      (TEM) and x-ray photoelectron spectroscopy (XPS) indicate that the silica-quantum
      dot nanocomposites consist of a layered structure. Owing to the amorphous, porous
      nature of a silica layer, the optical and photophysical properties of silica
      overcoated CdS:Mn/ZnS quantum dots are found to remain close to those of uncoated
      counterparts.

PMID- 15473815
TI  - Oxygen vacancies on TiO2 (110) from first principles calculations.
AB  - We have carried out a systematic study of oxygen vacancy formation on the TiO2
      (110) surface by means of plane-wave pseudopotential density-functional theory
      calculations. We have used models with the mean number of vacancies per surface
      unit cell being theta=0.25 and theta=0.5. The study comprises several kind of
      vacancies within the outermost layers of the surface. The use of a suitable set
      of technical parameter is often essential in order to get accurate results. We
      find that the presence of bridging vacancies is energetically favored in
      accordance to experimental data, although the formation of sub-bridging vacancies
      might be possible at moderate temperatures. Surprisingly, the spin state of the
      vacancy has little influence on the results. Atomic displacements are also
      analyzed and found to be strongly dependent on the particular arrangement of
      vacancies.

PMID- 15473816
TI  - A first-principles potential energy surface and vibrational states for hydrogen
      on Cu(100).
AB  - Density-functional theory calculations based on plane-wave expansion and
      pseudopotential treatment were carried out for atomic hydrogen on a rigid Cu(100)
      surface. A global potential energy surface was then obtained by using a three
      dimensional spline interpolation. It is found that the minimum of the potential
      is located at the fourfold hollow site with a diffusion barrier of 88 meV at the
      bridge site. The vibrational states of atomic hydrogen and deuterium on the
      Cu(100) surface were calculated on the potential surface. Our calculations show
      that the vibrational states A(1) (0), A(1) (1), E(1), and B(2) (1) of H/Cu(100)
      exhibit strong localized character and very narrow band widths, whereas other
      excited vibrational states have considerable delocalized character and broad band
      widths. The vibrational frequency of 71.2 (51.5) meV for H(D) in the
      perpendicular direction obtained in this study is in good agreement with the
      experimentally observed value of 70 (52) meV.

PMID- 15473817
TI  - Polyhedral ground states in clusters of asymmetric hard sphere ions.
AB  - Clusters of hard sphere ions with sufficient size asymmetry to stabilize a
      tetrahedral structure in the bulk are found to exhibit trivalent polyhedral
      ground states in clusters of up to roughly 200 ions. The map of cluster ground
      state structures over the space of cluster size and ion asymmetry is presented.

PMID- 15473818
TI  - Dynamic interfacial effect of electroosmotic slip flow with a moving capillary
      front in hydrophobic circular microchannels.
AB  - Miniaturization of chemical analysis using microfabrication is an emerging
      technology. The use of polymeric materials as opposed to conventional glass
      substrate is also a promising alternative. As most polymeric materials are
      hydrophobic relative to glass, we describe here the implication for the loading
      process of electroosmotic flow (EOF) when a three-phase (solid-liquid-vapor)
      contact line exists. The presence of these interfaces can result in a large
      Laplace pressure that resists EOF and hence hinders its flow performance. This
      effect depends on the phenomenological contact angle at the solid-liquid
      interface. In our model for EOF, we considered simultaneously the presence of an
      electric double layer, liquid slips via a weaker solid-liquid interaction and
      Laplace pressure across a liquid-vapor interface.

PMID- 15473819
TI  - Structure of Lennard-Jones fluids confined in square nanoscale channels from
      density functional theory.
AB  - The density distribution of Lennard-Jones fluids confined in square nanoscale
      channels with Lennard-Jones walls has been studied using the nonlocal density
      functional theory (DFT) based on the Tarazona model. The effect of channel
      lengths on the density profiles with various chemical potentials was discussed.
      It was found that there is an apparent layering phenomenon for the confined
      fluids due to the combining influences of the enhancing solid-fluid interaction
      and the excluded volume effect. The pronounced density peaks were observed at the
      corners of square channels due to the strong fluid-solid interactions. The grand
      canonical ensemble Monte Carlo simulation (GCEMC) was applied to test the
      nonlocal DFT results. The DFT calculations are in relatively good agreement with
      the GCEMC simulations. The adsorption isotherms in a series of square channels
      were evaluated based on the obtained density distributions. The adsorption
      mechanism within the square pores was investigated. A comparison between the
      adsorptions of the square pores with those of the corresponding slit-size pores
      has been given.

PMID- 15473820
TI  - Optical properties of Cu nanoclusters supported on MgO(100).
AB  - The vertical transitions of Cu atoms, dimers, and tetramers deposited on the MgO
      surface have been investigated by means of ab initio calculations based either on
      complete active space second-order perturbation theory or on time-dependent
      density functional theory. Three adsorption sites have been considered as
      representative of the complexity of the MgO surface: regular sites at flat (100)
      terraces, extended defects such as monoatomic steps, and point defects such as
      neutral oxygen vacancies (F or color centers). The optical properties of the
      supported Cu clusters have been compared with those of the corresponding gas
      phase units. Upon deposition a substantial modification of the energy levels of
      the supported cluster is induced by the Pauli repulsion with the substrate. This
      causes shifts in the optical transitions going from free to supported clusters.
      The changes in cluster geometry induced by the substrate have a much smaller
      effect on the optical absorption bands. On F centers the presence of filled
      impurity levels in the band gap of MgO results in a strong mixing with the empty
      levels of the Cu atoms and clusters with consequent deep changes in the optical
      properties of the color centers. The results allow to interpret electron energy
      loss spectra of Cu atoms deposited on MgO thin films.

PMID- 15473821
TI  - Van der Waals interactions in a dielectric with continuously varying dielectric
      function.
AB  - We formulate and evaluate the van der Waals part of the free energy due to a
      dielectric profile that varies continuously throughout the space between two
      interacting bodies. Not considering the work needed to create the inhomogeneous
      dielectric profile, focusing only on that part of the free energy affected by the
      inhomogeneity, we compare the ensuing interaction free energy with that of the
      original Lifshitz formulation with its step function changes at material
      boundaries and uniform dielectric medium. Rather than the monotonically varying
      attraction between like bodies given by the original formulation, the
      inhomogeneous continuous dielectric function leads to attractions as well as
      repulsions. The Lifshitz result emerges naturally in the limit of separations
      much larger than the thickness of the interfaces.

PMID- 15473822
TI  - Interatomic Lennard-Jones potentials of linear and branched alkanes calibrated by
      Gibbs ensemble simulations for vapor-liquid equilibria.
AB  - We propose Lennard-Jones potential parameters for interatomic interactions of
      linear and branched alkanes based on matching the results of Gibbs ensemble
      simulations of vapor-liquid equilibria to experimental data. The alkane model is
      similar as in the OPLS-AA, but multiple atom types for carbon based on the number
      of covalently bonded hydrogen atoms are necessary to accurately reproduce liquid
      densities and enthalpies of vaporization with the errors of 2.1% and 3.3%,
      respectively, for hydrocarbons of various chain lengths and structures. We find
      that the attraction energies of the carbon atoms are almost proportional to the
      number of covalent hydrogen atoms with each increasing the carbon energy
      parameter by approximately 0.033 kcal/mol. Though the present force field
      outperforms the OPLS-AA force field for alkanes we studied, systematic deviations
      for vapor pressures are still observed with errors of 15%-30%, and critical
      temperatures are slightly underestimated. We think that these shortcomings are
      probably due to the inadequacy of the two-parameter Lennard-Jones potential, and
      especially its behavior at short distances.

PMID- 15473823
TI  - Kinetics of a polysoap collapse.
AB  - We study the dynamics of collapse of a polysoap by means of large-scale molecular
      dynamics simulation and scaling arguments. A polysoap consists of a hydrophilic
      backbone and hydrophobic side chains attached at regular intervals along the
      backbone. In selective solvent conditions, the hydrophobic components aggregate,
      forcing the hydrophilic backbone to form loops anchored at the surface of the
      core, ultimately forming a micelle. The kinetics of polysoap collapse includes
      two major mechanisms: (1) early aggregation of the hydrophobic side chains
      controlled by first-order kinetics whose rate constant is given by a contact
      probability and (2) coalescence into larger clusters which requires activation to
      overcome energy barriers due to excluded volume repulsions between intermediate
      micelle coronas. In the late stage, the energy barrier is increasing as p(3/2),
      with p the number of aggregated side chains in an intermediate micelle. The
      corresponding late-stage rate constant decays exponentially as approximately exp(
      p(3/2)).

PMID- 15473824
TI  - Thermodynamic behaviors of polyampholytes at low temperatures.
AB  - The thermodynamic properties of 6-mer polyampholyte chains were simulated with
      the multicanonical Monte Carlo method in a three-dimensional off-lattice model.
      The results demonstrate that the number of the charged monomers on the chain and
      the sequence significantly affect the transition behaviors of polyampholyte
      chains. In the case of the random distribution of the charged monomers, two
      oppositely charged monomers act as two stickers during a collapse process, due to
      which the movement of monomers is suppressed and the chains can more directly
      reach their solid state. Interestingly, in a proper arrangement of the charged
      monomers, the chains may have a proteinlike nondegenerate state, i.e., the chain
      is designable. The transition of such polyampholyte chains appears to be of a two
      state, all-or-none type.

PMID- 15473825
TI  - Shear-induced phase separation in "nonentangled" oligomer mixture.
AB  - Shear-induced phase separation was found in "nonentangled" oligomer mixture. The
      sheared mixture in one phase becomes turbid and its scattering pattern exhibits
      so-called "butterfly pattern" which is commonly observed in shear-induced phase
      separation of semidilute polymer solutions. The origin of the shear-induced phase
      separation is found to be dynamical asymmetry due to the difference in the glass
      transition temperature.

PMID- 15473826
TI  - Smooth transition from metastability to instability in phase separating protein
      solutions.
AB  - For insight into the structure and dynamics of phases emerging upon crossing the
      metastability/instability boundary we monitor with optical microscopy, in real
      time and in real space, the generation of a dense liquid phase in high
      concentration solutions of the protein lysozyme after temperature quenches into
      thermodynamically defined metastable and unstable regions. We show with this
      system, which is a poor fit to mean-field assumptions, that the evolution of the
      structure factor during nucleation is similar to that during spinodal
      decomposition and reveals no singularity predicted upon crossing the
      metastability boundary. We introduce two kinetic definitions of the
      metastability/instability boundary that yield values within approximately 1.5 K,
      i.e., the boundary appears as an area rather than a line, which is near and above
      the thermodynamic prediction. Delay times for the appearance of the new phase in
      the unstable regime are significant, i.e., new-phase growth is hindered by
      kinetic barriers. While our results agree with predictions of the non-mean-field
      theories of phase transformations, the experimentally observed behavior is richer
      than the one envisioned by theory.

PMID- 15473827
TI  - Interdiffusion of solvent into glassy polymer films: a molecular dynamics study.
AB  - Large scale molecular dynamics and grand canonical Monte Carlo simulation
      techniques are used to study the behavior of the interdiffusion of a solvent into
      an entangled polymer matrix as the state of the polymer changes from a melt to a
      glass. The weight gain by the polymer increases with time t as t(1/2) in
      agreement with Fickian diffusion for all cases studied, although the diffusivity
      is found to be strongly concentration dependent especially as one approaches the
      glass transition temperature of the polymer. The diffusivity as a function of
      solvent concentration determined using the one-dimensional Fick's model of the
      diffusion equation is compared to the diffusivity calculated using the Darken
      equation from simulations of equilibrated solvent-polymer solutions. The
      diffusivity calculated using these two different approaches are in good
      agreement. The behavior of the diffusivity strongly depends on the state of the
      polymer and is related to the shape of the solvent concentration profile.

PMID- 15473829
TI  - Nonlinear ac responses of electro-magnetorheological fluids.
AB  - We apply a Langevin model to investigate the nonlinear ac responses of electro
      magnetorheological (ERMR) fluids under the application of two crossed dc magnetic
      (z axis) and electric (x axis) fields and a probing ac sinusoidal magnetic field.
      We focus on the influence of the magnetic fields which can yield nonlinear
      behaviors inside the system due to the particles with a permanent magnetic dipole
      moment. Based on a perturbation approach, we extract the harmonics of the
      magnetic field and orientational magnetization analytically. To this end, we find
      that the harmonics are sensitive to the degree of anisotropy of the structure as
      well as the field frequency. Thus, it is possible to real-time-monitor the
      structure transformation of ERMR fluids by detecting the nonlinear ac responses.

PMID- 15473828
TI  - Spontaneous three-dimensional nanostructure formation of perfluoroalkyl
      terminated liquid crystal: a molecular dynamics simulation study.
AB  - Structure formation of a perfluoroalkyl terminated liquid crystal molecule was
      studied by molecular dynamics simulations. Two distinct structures with smectic-C
      like layers and with bundles (blocks) of collapsed layers were spontaneously
      formed depending on the simulation temperatures. The bundles in the latter
      structure were somewhat positionally ordered (with respect to the small angle
      spots in its structure function) and orientationally isotropic overall even
      though the molecules making each bundle were well oriented. These characteristics
      of the simulated system well correspond to the cubic phase of the real system,
      and an even more precisely correspond to the proposed cubic structure model with
      respect to its hierarchical structure.

PMID- 15473830
TI  - Saddles and softness in simple model liquids.

PMID- 15473832
TI  - Phloxine B phototoxicity: a mechanistic study using HaCaT keratinocytes.
AB  - Phloxine B (PhB) (2',4',5',7'-tetrabromo-4,5,6,7-tetrachlorofluorescein; D&C Red
      No. 28) is a red dye found in drugs, cosmetics and foods; it is also currently
      being evaluated as a phototoxin for the potential control of fruit flies.
      Previous studies have shown that PhB is an efficient photosensitizer of damage to
      cellular membranes; thus, exposure of the skin to the dye and sunlight or
      artificial light may result in phototoxicity. Therefore, we have studied the
      phototoxicity of PhB and its structural analogue 2',7'-dichlorofluorescein (DCF)
      to HaCaT keratinocytes. Anaerobic visible irradiation (>400 nm) of PhB generated
      a semiquinone type radical, as detected by direct electron paramagnetic
      resonance. Aerobic visible irradiation of a reaction mixture containing PhB, the
      spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and nicotinamide adenine
      dinucleotide (reduced) generated a superoxide dismutase-sensitive DMPO/O(2)(.-)
      adduct. Irradiation of PhB and DCF in D(2)O generated singlet oxygen with quantum
      yields of 0.59 and 0.06, respectively. PhB was much more phototoxic than DCF when
      cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Visible irradiation
      of HaCaT keratinocytes in the presence of PhB (5 micro M) resulted in a 90%
      decrease in cell viability. 3beta-Hydroxy-5alpha-cholest-6-ene-5-hydroperoxide, a
      singlet oxygen photoproduct of cholesterol, was isolated from HaCaT keratinocytes
      irradiated in the presence of PhB. Furthermore, PhB phototoxicity was inhibited
      by histidine and cysteine, quenchers of singlet oxygen. PhB (0.5 microM) and
      light irradiation also resulted in DNA damage, as measured by the Comet assay.
      The phototoxicity mechanism of PhB most probably initially involves a Type-II
      reaction with free radicals playing a minor role. However, secondary oxidative
      species such as radicals generated as a result of lipid peroxidation may serve to
      further promote oxidative damage. Our findings suggest that concern is warranted
      about the use of this dye in cosmetic products, as a food additive and in
      insecticidal sprays.

PMID- 15473833
TI  - The budding yeast spindle pole body: structure, duplication, and function.
AB  - Nucleation of microtubules by eukaryotic microtubule organizing centers (MTOCs)
      is required for a variety of functions, including chromosome segregation during
      mitosis and meiosis, cytokinesis, fertilization, cellular morphogenesis, cell
      motility, and intracellular trafficking. Analysis of MTOCs from different
      organisms shows that the structure of these organelles is widely varied even
      though they all share the function of microtubule nucleation. Despite their
      morphological diversity, many components and regulators of MTOCs, as well as
      principles in their assembly, seem to be conserved. This review focuses on one of
      the best-characterized MTOCs, the budding yeast spindle pole body (SPB). We
      review what is known about its structure, protein composition, duplication,
      regulation, and functions. In addition, we discuss how studies of the yeast SPB
      have aided investigation of other MTOCs, most notably the centrosome of animal
      cells.

PMID- 15473834
TI  - Plasmodium sporozoite molecular cell biology.
AB  - Plasmodium sporozoites display complex phenotypes including gliding motility and
      invasion of and transmigration through cells in the mosquito vector and the
      vertebrate host. Sporozoite studies have been difficult to perform because of
      technical concerns. Nevertheless, they have already provided insights into
      several aspects of sporozoite biology, shared in part with other apicomplexan
      invasive stages. Structure/function analysis of the thrombospondin-related
      anonymous protein paved the way to the understanding of the molecular mechanisms
      of apicomplexan gliding motility and host cell invasion. Functional studies of
      circumsporozoite protein revealed its role in Plasmodium sporozoite morphogenesis
      in addition to its well-known function in host cell invasion. Transcriptional
      surveys, which facilitate the investigation of gene expression programs that
      control sporozoite phenotypes, have revealed a high degree of previously
      unappreciated complexity and novel proteins that mediate sporozoite host cell
      infection.

PMID- 15473835
TI  - Regulation of muscle mass by myostatin.
AB  - Myostatin is a secreted protein that acts as a negative regulator of skeletal
      muscle mass. During embryogenesis, myostatin is expressed by cells in the myotome
      and in developing skeletal muscle and acts to regulate the final number of muscle
      fibers that are formed. During adult life, myostatin protein is produced by
      skeletal muscle, circulates in the blood, and acts to limit muscle fiber growth.
      The existence of circulating tissue-specific growth inhibitors of this type was
      hypothesized over 40 years ago to explain how sizes of individual tissues are
      controlled. Skeletal muscle appears to be the first example of a tissue whose
      size is controlled by this type of regulatory mechanism, and myostatin appears to
      be the first example of the long-sought chalone.

PMID- 15473836
TI  - Bi-directional protein transport between the ER and Golgi.
AB  - The endoplasmic reticulum (ER) and the Golgi comprise the first two steps in
      protein secretion. Vesicular carriers mediate a continuous flux of proteins and
      lipids between these compartments, reflecting the transport of newly synthesized
      proteins out of the ER and the retrieval of escaped ER residents and vesicle
      machinery. Anterograde and retrograde transport is mediated by distinct sets of
      cytosolic coat proteins, the COPII and COPI coats, respectively, which act on the
      membrane to capture cargo proteins into nascent vesicles. We review the
      mechanisms that govern coat recruitment to the membrane, cargo capture into a
      transport vesicle, and accurate delivery to the target organelle.

PMID- 15473837
TI  - The role of knox genes in plant development.
AB  - knox genes encode homeodomain-containing transcription factors that are required
      for meristem maintenance and proper patterning of organ initiation. In plants
      with simple leaves, knox genes are expressed exclusively in the meristem and
      stem, but in dissected leaves, they are also expressed in leaf primordia,
      suggesting that they may play a role in the diversity of leaf form. This
      hypothesis is supported by the intriguing phenotypes found in gain-of-function
      mutations where knox gene misexpression affects leaf and petal shape. Similar
      phenotypes are also found in recessive mutations of genes that function to
      negatively regulate knox genes. KNOX proteins function as heterodimers with other
      homeodomains in the TALE superclass. The gibberellin and lignin biosynthetic
      pathways are known to be negatively regulated by KNOX proteins, which results in
      indeterminate cell fates.

PMID- 15473838
TI  - Adaptors for clathrin coats: structure and function.
AB  - Clathrin-coated vesicles (CCVs) are responsible for the transport of proteins
      between various compartments of the secretory and endocytic systems. Clathrin
      forms a scaffold around these vesicles that is linked to membranes by clathrin
      adaptors. The adaptors simultaneously bind to clathrin and to transmembrane
      proteins and/or phospholipids and can also interact with each other and with
      other components of the CCV formation machinery. The result is a collection of
      proteins that can make multiple, moderate strength (microM Kd) interactions and
      thereby establish the dynamic regulatable networks to drive vesicle genesis at
      the correct time and place in the cell. This review focuses on the structure of
      clathrin adaptors and how these structures provide functional information on the
      mechanism of CCV formation.

PMID- 15473839
TI  - The engulfment process of programmed cell death in caenorhabditis elegans.
AB  - Programmed cell death involves the removal of cell corpses by other cells in a
      process termed engulfment. Genetic studies of the nematode Caenorhabditis elegans
      have led to a framework not only for the killing step of programmed cell death
      but also for the process of cell-corpse engulfment. This work has defined two
      signal transduction pathways that act redundantly to control engulfment. Signals
      expressed by dying cells probably regulate these C. elegans pathways. Components
      of the cell-corpse recognition system of one of the C. elegans pathways include
      the CED-7 ABC transporter, which likely presents a death ligand on the surface of
      the dying cell; the CED-1 transmembrane receptor, which recognizes this signal;
      and the CED-6 adaptor protein, which may transduce a signal from CED-1. The
      second C. elegans pathway acts in parallel and involves a novel Rac GTPase
      signaling pathway, with the components CED-2 CrkII, CED-5 DOCK180, CED-12 ELMO,
      and CED-10 Rac. The cell-corpse recognition system that activates this pathway
      remains to be characterized. In C. elegans, and possibly in mammals, the process
      of cell-corpse engulfment promotes the death process itself. The known mechanisms
      for cell-corpse engulfment leave much to be discovered concerning this
      fundamental aspect of metazoan biology.

PMID- 15473840
TI  - Chemoattractant signaling in dictyostelium discoideum.
AB  - Dictyostelium is an accessible organism for studies of signaling via
      chemoattractant receptors. Chemoattractant-mediated signaling events and
      components are reviewed and presented as a series of connected modules, including
      excitation, inhibition, G protein-independent responses, early gene expression,
      inositol lipids, PH domain-containing proteins, cyclic AMP signaling,
      polarization acquisition, actin polymerization, and cortical myosin. The network
      incorporates information from biochemical, genetic, and cell biological
      experiments carried out on living cells. The modules and connections represent
      current understanding, and future information is expected to modify and build
      upon this structure.

PMID- 15473841
TI  - Laminin functions in tissue morphogenesis.
AB  - Significant advances have been made in the application of genetics to probe the
      functions of basement membrane laminins. These studies have shown that different
      laminin subunits profoundly affect tissue morphogenesis, starting around the time
      of embryonic implantation and extending through organogenesis and into the
      postnatal period. Collectively they have revealed common functions that include
      the induction and maintenance of cell polarity, the establishment of barriers
      between tissue compartments, the organization of cells into tissues, and the
      protection of adherent cells from detachment-induced cell death, anoikis.
      Interpreted in light of what is known about laminin structure and self-assembly
      and binding activities, these advances have begun to provide insights into
      mechanisms of action. In this review we focus on the contributions of the
      laminins in invertebrate and vertebrate tissue morphogenesis.

PMID- 15473843
TI  - New developments in mitochondrial assembly.
AB  - The mitochondrion has developed an elaborate translocation system for the import
      of nuclear-coded proteins and the export of proteins coded on the mitochondrial
      genome. Precursor proteins contain targeting and sorting information to reach the
      mitochondrion, whereas the translocons recognize the information and direct the
      precursor to the correct compartment. The outer membrane contains the TOM
      (translocase of the outer membrane) complex for translocation and the SAM
      (sorting and assembly machinery) complex for assembly of outer membrane proteins
      with complex topologies. At the inner membrane, the TIM23 (translocase of the
      inner membrane) mediates the import of mitochondrial proteins with a typical N
      terminal targeting sequence, and the TIM22 complex mediates the import of
      polytopic inner membrane proteins. Based on its prokaryotic origin, the inner
      membrane also contains several components that mediate the export and assembly of
      proteins from within the matrix. Together the translocation and assembly
      complexes coordinate assembly of the mitochondrion.

PMID- 15473842
TI  - Dorsal-ventral patterning and neural induction in Xenopus embryos.
AB  - We review the current status of research in dorsal-ventral (D-V) patterning in
      vertebrates. Emphasis is placed on recent work on Xenopus, which provides a
      paradigm for vertebrate development based on a rich heritage of experimental
      embryology. D-V patterning starts much earlier than previously thought, under the
      influence of a dorsal nuclear -Catenin signal. At mid-blastula two signaling
      centers are present on the dorsal side: The prospective neuroectoderm expresses
      bone morphogenetic protein (BMP) antagonists, and the future dorsal endoderm
      secretes Nodal-related mesoderm-inducing factors. When dorsal mesoderm is formed
      at gastrula, a cocktail of growth factor antagonists is secreted by the Spemann
      organizer and further patterns the embryo. A ventral gastrula signaling center
      opposes the actions of the dorsal organizer, and another set of secreted
      antagonists is produced ventrally under the control of BMP4. The early dorsal 
      Catenin signal inhibits BMP expression at the transcriptional level and promotes
      expression of secreted BMP antagonists in the prospective central nervous system
      (CNS). In the absence of mesoderm, expression of Chordin and Noggin in ectoderm
      is required for anterior CNS formation. FGF (fibroblast growth factor) and IGF
      (insulin-like growth factor) signals are also potent neural inducers. Neural
      induction by anti-BMPs such as Chordin requires mitogen-activated protein kinase
      (MAPK) activation mediated by FGF and IGF. These multiple signals can be
      integrated at the level of Smad1. Phosphorylation by BMP receptor stimulates
      Smad1 transcriptional activity, whereas phosphorylation by MAPK has the opposite
      effect. Neural tissue is formed only at very low levels of activity of BMP
      transducing Smads, which require the combination of both low BMP levels and high
      MAPK signals. Many of the molecular players that regulate D-V patterning via
      regulation of BMP signaling have been conserved between Drosophila and the
      vertebrates.

PMID- 15473844
TI  - The adenomatous polyposis coli protein: the Achilles heel of the gut epithelium.
AB  - The Adenomatous Polyposis coli (APC) gene is mutated or lost in most colon
      cancers, and the APC protein has emerged as a multifunctional protein that is not
      only involved in the Wnt-regulated degradation of -catenin, but also regulates
      cytoskeletal proteins and thus plays a role in cell migration, cell adhesion, and
      mitosis. The gut epithelium is uniquely dependent on an intricate balance between
      a number of fundamental cellular processes including migration, differentiation,
      adhesion, apoptosis, and mitosis. In this review, I discuss the molecular
      mechanisms that govern the various functions of APC and their relationship to the
      role of APC in colon cancer.

PMID- 15473845
TI  - Cell biology of mycobacterium tuberculosis phagosome.
AB  - Phagocytosis and phagolysosome biogenesis represent fundamental biological
      processes essential for proper tissue homeostasis, development, elimination of
      invading microorganisms, and antigen processing and presentation. Phagosome
      formation triggers a preprogrammed pathway of maturation into the phagolysosome,
      a process controlled by Ca2+ and the regulators of organellar trafficking
      centered around the small GTP-binding proteins Rabs and their downstream
      effectors, including lipid kinases, organellar tethering molecules, and membrane
      fusion apparatus. Mycobacterium tuberculosis is a potent human pathogen
      parasitizing macrophages. It interferes with the Rab-controlled membrane
      trafficking and arrests the maturing phagosome at a stage where no harm can be
      done to the pathogen while the delivery of nutrients and membrane to the vacuole
      harboring the microorganism continues. This process, referred to as the M.
      tuberculosis phagosome maturation arrest or inhibition of phagosome-lysosome
      fusion, is critical for M. tuberculosis persistence in human populations. It also
      provides a general model system for dissecting the phagolysosome biogenesis
      pathways. Here we review the fundamental trafficking processes targeted by M.
      tuberculosis and the mycobacterial products that interfere with phagosomal
      maturation.

PMID- 15473846
TI  - Retrovirus budding.
AB  - Human immunodeficiency virus (HIV) and other retroviruses acquire their envelopes
      and spread infection by budding through the limiting membranes of producer cells.
      To facilitate budding, retroviruses usurp a cellular pathway that is normally
      used to create vesicles that bud into late endosomal compartments called
      multivesicular bodies (MVB). Research on yeast and human MVB biogenesis has led
      to the identification of 25 human proteins that are required for vesicle
      formation and for HIV-1 budding, and has produced a working model for sequential
      recruitment of these proteins during MVB vesicle formation. Retroviruses can
      redirect this machinery to the plasma membrane and leave the cell in a single
      step or, alternatively, can bud directly into MVB compartments and then exit
      cells via the exosome pathway. Remarkably, virus release from both the plasma
      membrane and MVB compartments can occur directionally into specialized sites of
      cell-to-cell contact called virological synapses. Thus retroviruses have evolved
      elaborate mechanisms for escaping the cell and maximizing their chances of
      infecting a new host.

PMID- 15473847
TI  - Asymmetric cell division in C. elegans: cortical polarity and spindle
      positioning.
AB  - The one-cell Caenorhabditis elegans embryo divides asymmetrically into a larger
      and smaller blastomere, each with a different fate. How does such asymmetry
      arise? The sperm-supplied centrosome establishes an axis of polarity in the
      embryo that is transduced into the establishment of anterior and posterior
      cortical domains. These cortical domains define the polarity of the embryo,
      acting upstream of the PAR proteins. The PAR proteins, in turn, determine the
      subsequent segregation of fate determinants and the plane of cell division. We
      address how cortical asymmetry could be established, relying on data from C.
      elegans and other polarized cells, as well as from applicable models. We discuss
      how cortical polarity influences spindle position to accomplish an asymmetric
      division, presenting the current models of spindle orientation and anaphase
      spindle displacement. We focus on asymmetric cell division as a function of the
      actin and microtubule cytoskeletons, emphasizing the cell biology of polarity.

PMID- 15473848
TI  - Nuclear receptors in macrophage biology: at the crossroads of lipid metabolism
      and inflammation.
AB  - Macrophages are essential modulators of lipid metabolism and the innate immune
      system. Lipid and inflammatory pathways induced in activated macrophages are
      central to the pathogenesis of human diseases including atherosclerosis. Recent
      work has shown that expression of genes involved in lipid uptake and cholesterol
      efflux in macrophages is controlled by peroxisome proliferator-activated
      receptors (PPARs) and liver X receptors (LXRs). Other studies have implicated
      these same receptors in the modulation of macrophage inflammatory gene
      expression. Together, these observations position PPARs and LXRs at the
      crossroads of lipid metabolism and inflammation and suggest that these receptors
      may serve to integrate these pathways in the control of macrophage gene
      expression. In this review, we summarize recent work that has advanced our
      understanding of the roles of PPARs and LXRs in macrophage biology and discuss
      the implication of these results for cardiovascular physiology and disease.

PMID- 15473849
TI  - Membrane trafficking in plants.
AB  - Plant membrane trafficking shares many features with other eukaryotic organisms,
      including the machinery for vesicle formation and fusion. However, the plant
      endomembrane system lacks an ER-Golgi intermediate compartment, has numerous
      Golgi stacks and several types of vacuoles, and forms a transient compartment
      during cell division. ER-Golgi trafficking involves bulk flow and efficient
      recycling of H/KDEL-bearing proteins. Sorting in the Golgi stacks separates bulk
      flow to the plasma membrane from receptor-mediated trafficking to the lytic
      vacuole. Cargo for the protein storage vacuole is delivered from the endoplasmic
      reticulum (ER), cis-Golgi, and trans-Golgi. Endocytosis includes recycling of
      plasma membrane proteins from early endosomes. Late endosomes appear identical
      with the multivesiculate prevacuolar compartment that lies on the Golgi-vacuole
      trafficking pathway. In dividing cells, homotypic fusion of Golgi-derived
      vesicles forms the cell plate, which expands laterally by targeted vesicle fusion
      at its margin, eventually fusing with the plasma membrane.

PMID- 15473850
TI  - RNA translation in axons.
AB  - The cell body has classically been considered the exclusive source of axonal
      proteins. However, significant evidence has accumulated recently to support the
      view that protein synthesis can occur in axons themselves, remote from the cell
      body. Indeed, local translation in axons may be integral to aspects of
      synaptogenesis, long-term facilitation, and memory storage in invertebrate axons,
      and for growth cone navigation in response to environmental stimuli in developing
      vertebrate axons. Here we review the evidence supporting mRNA translation in
      axons and discuss the potential roles that local protein synthesis may play
      during development and subsequent neuronal function. We advance the view that
      local translation provides a rapid supply of nascent proteins in restricted
      axonal compartments that can potentially underlie long-term responses to
      transient stimuli.

PMID- 15473851
TI  - The genetics and molecular biology of the synaptonemal complex.
AB  - The synaptonemal complex (SC) is a protein lattice that resembles railroad tracks
      and connects paired homologous chromosomes in most meiotic systems. The two side
      rails of the SC, known as lateral elements (LEs), are connected by proteins known
      as transverse filaments. The LEs are derived from the axial elements of the
      chromosomes and play important roles in chromosome condensation, pairing,
      transverse filament assembly, and prohibiting double-strand breaks (DSBs) from
      entering into recombination pathways that involve sister chromatids. The proteins
      that make up the transverse filaments of the SC also play a much earlier role in
      committing a subset of DSBs into a recombination pathway, which results in the
      production of reciprocal meiotic crossovers. Sites of crossover commitment can be
      observed as locations where the SC initiates and as immunostaining foci for a set
      of proteins required for the processing of DSBs to mature crossovers. In most
      (but not all) organisms it is the establishment of sites marking such crossover
      committed DSBs that facilitates completion of synapsis (full-length extension of
      the SC). The function of the mature full-length SC may involve both the
      completion of meiotic recombination at the DNA level and the exchange of the
      axial elements of the two chromatids involved in the crossover. However, the
      demonstration that the sites of crossover formation are designated prior to SC
      formation, and the finding that these sites display interference, argues against
      a role of the mature SC in mediating the process of interference. Finally, in at
      least some organisms, modifications of the SC alone are sufficient to ensure
      meiotic chromosome segregation in the complete absence of meiotic recombination.

PMID- 15473852
TI  - Mechanisms of polarized growth and organelle segregation in yeast.
AB  - Cell polarity, as reflected by polarized growth and organelle segregation during
      cell division in yeast, appears to follow a simple hierarchy. On the basis of
      physical cues from previous cell cycles or stochastic processes, yeast cells
      select a site for bud emergence that also defines the axis of cell division. Once
      polarity is established, rho protein-based signal pathways set up a polarized
      cytoskeleton by activating localized formins to nucleate and assemble polarized
      actin cables. These serve as tracks for the transport of secretory vesicles, the
      segregation of the trans Golgi network, the vacuole, peroxisomes, endoplasmic
      reticulum, mRNAs for cell fate determination, and microtubules that orient the
      nucleus in preparation for mitosis, all by myosin-Vs encoded by the MYO2 and MYO4
      genes. Most of the proteins participating in these processes in yeast are
      conserved throughout the kingdoms of life, so the emerging models are likely to
      be generally applicable. Indeed, several parallels to cellular organization in
      animals are evident.

PMID- 15473853
TI  - Cortical neuronal migration mutants suggest separate but intersecting pathways.
AB  - During brain development, neurons migrate great distances from proliferative
      zones to generate the cortical gray matter. A series of studies has identified
      genes that are critical for migration and targeting of neurons to specific brain
      regions. These genes encode three basic groups of proteins and produce three
      distinct phenotypes. The first group encodes cytoskeletal molecules and produces
      graded and dosage-dependent effects, with a significant amount of functional
      redundancy. This group also appears to play important roles during the initiation
      and ongoing progression of neuronal movement. The second group encodes signaling
      molecules for which homozygous mutations lead to an inverted cortex. In addition,
      this group is responsible for movement of neurons through anatomic boundaries to
      specific cortical layers. The third group encodes enzymatic regulators of
      glycosylation and appears to delineate where neuronal migration will arrest.
      There is significant cross-talk among these different groups of molecules,
      suggesting possible points of pathway convergence.

PMID- 15473854
TI  - Specification of temporal identity in the developing nervous system.
AB  - The nervous system of higher organisms exhibits extraordinary cellular diversity
      owing to complex spatial and temporal patterning mechanisms. The role of spatial
      patterning in generating neuronal diversity is well known; here we discuss how
      neural progenitors change over time to contribute to cell diversity within the
      central nervous system (CNS). We focus on five model systems: the vertebrate
      retina, cortex, hindbrain, spinal cord, and Drosophila neuroblasts. For each, we
      address the following questions: Do multipotent progenitors generate different
      neuronal cell types in an invariant order? Do changes in progenitor-intrinsic
      factors or progenitor-extrinsic signals regulate temporal identity (i.e., the
      sequence of neuronal cell types produced)? What is the mechanism that regulates
      temporal identity transitions; i.e., what triggers the switch from one temporal
      identity to the next? By applying the same criteria to analyze each model system,
      we try to highlight common themes, point out unique attributes of each system,
      and identify directions for future research.

PMID- 15473855
TI  - Myosin VI: cellular functions and motor properties.
AB  - Myosin motor proteins use the energy derived from ATP hydrolysis to move cargo
      along actin tracks. Myosin VI, unlike almost all other myosins, moves toward the
      minus end of actin filaments and functions in a variety of intracellular
      processes such as vesicular membrane traffic, cell migration, and mitosis. These
      diverse roles of myosin VI are mediated by interaction with a number of different
      binding partners present in multi-protein complexes. Myosin VI can work in vitro
      as a processive dimeric motor and as a nonprocessive monomeric motor, each with a
      large working stroke. The possibility that both monomeric and dimeric forms of
      myosin VI operate in the cell may represent an important regulatory mechanism for
      controlling the multiple steps in transport pathways where nonprocessive and
      processive motors are required.

PMID- 15473856
TI  - Cellular length control systems.
AB  - The problem of organelle size control can be addressed most simply by considering
      cellular structures that are linear, so that their size can be defined by a
      single parameter: length. We compare existing studies on several linear
      biological structures including prokaryotic flagella and flagellar hooks,
      eukaryotic flagella, sarcomere thin filaments, and microvilli. In some cases,
      existing evidence strongly supports the idea that length control involves a
      molecular ruler, in which the size of the overall structure is compared with the
      size of an individual molecule. In other cases, length control is likely to
      involve a steady-state balance of assembly and disassembly, in which one or the
      other rate is inherently length dependent. The lessons learned from size control
      in linear structures should be applicable to organelles with more complex three
      dimensional structures.

PMID- 15473857
TI  - Signaling pathways in intestinal development and cancer.
AB  - The study of the epithelium of the adult mammalian intestine touches upon many
      modern aspects of biology. The epithelium is in a constant dialogue with the
      underlying mesenchyme to control stem cell activity, proliferation in transit
      amplifying compartments, lineage commitment, terminal differentiation and,
      ultimately, cell death. There are spatially distinct compartments dedicated to
      each of these events. The Wnt, TGF-beta, BMP, Notch, and Par polarity pathways
      are the major players in homeostatic control of the adult epithelium. Several
      hereditary cancer syndromes deregulate these same signaling cascades through
      mutational (in)activation. Moreover, these mutations often also occur in sporadic
      tumors. Thus symmetry exists between the roles that these signaling pathways play
      in physiology and in cancer of the intestine. This is particularly evident for
      the Wnt/APC pathway, for which the mammalian intestine has become one of the most
      studied paradigms. Here, we integrate recent knowledge of the molecular inner
      workings of the prototype signaling cascades with their specific roles in
      intestinal epithelial homeostasis and in neoplastic transformation of the
      epithelium.

PMID- 15473858
TI  - Fundamentals of planarian regeneration.
AB  - The principles underlying regeneration in planarians have been explored for over
      100 years through surgical manipulations and cellular observations. Planarian
      regeneration involves the generation of new tissue at the wound site via cell
      proliferation (blastema formation), and the remodeling of pre-existing tissues to
      restore symmetry and proportion (morphallaxis). Because blastemas do not replace
      all tissues following most types of injuries, both blastema formation and
      morphallaxis are needed for complete regeneration. Here we discuss a
      proliferative cell population, the neoblasts, that is central to the regenerative
      capacities of planarians. Neoblasts may be a totipotent stem-cell population
      capable of generating essentially every cell type in the adult animal, including
      themselves. The population properties of the neoblasts and their descendants
      still await careful elucidation. We identify the types of structures produced by
      blastemas on a variety of wound surfaces, the principles guiding the
      reorganization of pre-existing tissues, and the manner in which scale and cell
      number proportions between body regions are restored during regeneration.

PMID- 15473859
TI  - Dynactin.
AB  - Dynactin is a multisubunit protein complex that is required for most, if not all,
      types of cytoplasmic dynein activity in eukaryotes. Dynactin binds dynein
      directly and allows the motor to traverse the microtubule lattice over long
      distances. A single dynactin subunit, p150Glued, is sufficient for both
      activities, yet dynactin contains several other subunits that are organized into
      an elaborate structure. It is currently believed that the bulk of the dynactin
      structure participates in interactions with a wide range of cellular structures,
      many of which are cargoes of the dynein motor. Genetic studies verify the
      importance of all elements of dynactin structure to its function. Although dynein
      can bind some membranous cargoes independently of dynactin, establishment of a
      fully functional dynein-cargo link appears to depend on dynactin. In this review,
      I summarize what is presently known about dynactin structure, the cellular
      structures with which it associates, and the intermolecular interactions that
      underlie and regulate binding. Although the molecular details of dynactin's
      interactions with membranous organelles and other molecules are complex, the
      framework provided here is intended to distill what is presently known and to be
      of use to dynactin specialists and beginners alike.

PMID- 15473860
TI  - The Wnt signaling pathway in development and disease.
AB  - Tight control of cell-cell communication is essential for the generation of a
      normally patterned embryo. A critical mediator of key cell-cell signaling events
      during embryogenesis is the highly conserved Wnt family of secreted proteins.
      Recent biochemical and genetic analyses have greatly enriched our understanding
      of how Wnts signal, and the list of canonical Wnt signaling components has
      exploded. The data reveal that multiple extracellular, cytoplasmic, and nuclear
      regulators intricately modulate Wnt signaling levels. In addition, receptor
      ligand specificity and feedback loops help to determine Wnt signaling outputs.
      Wnts are required for adult tissue maintenance, and perturbations in Wnt
      signaling promote both human degenerative diseases and cancer. The next few years
      are likely to see novel therapeutic reagents aimed at controlling Wnt signaling
      in order to alleviate these conditions.

PMID- 15473861
TI  - Connexins and cell signaling in development and disease.
AB  - Gap junctions contain hydrophilic membrane channels that allow direct
      communication between neighboring cells through the diffusion of ions,
      metabolites, and small cell signaling molecules. They are made up of a hexameric
      array of polypeptides encoded by the connexin multi-gene family. Cell-cell
      communication mediated by connexins is crucial to various cellular functions,
      including the regulation of cell growth, differentiation, and development.
      Mutations in connexin genes have been linked to a variety of human diseases,
      including cardiovascular anomalies, peripheral neuropathy, deafness, skin
      disorders, and cataracts. In addition to their coupling function, recent studies
      suggest that connexin proteins may also mediate signaling. This could involve
      interactions with other protein partners that may play a role not only in
      connexin assembly, trafficking, gating and turnover, but also in the coordinate
      regulation of cell-cell communication with cell adhesion and cell motility. The
      integration of these cell functions is likely to be important in the role of gap
      junctions in development and disease.

PMID- 15473862
TI  - Membrane domains.
AB  - Considerable evidence shows that lateral inhomogeneities in lipid composition and
      physical properties exist in biological membranes. These membrane lipid domains
      are proposed to play important roles in processes such as signal transduction and
      membrane traffic. However, there is not at present an adequate description of the
      nature of these lipid domains in terms of their size, abundance, composition, or
      dynamics. We discuss the current analyses of the properties and function of
      membrane domains in cells and compare their properties with chemically simpler
      model membrane systems that can be understood in greater detail.

PMID- 15473863
TI  - G protein control of microtubule assembly.
AB  - Microtubules are dynamic polymers required for many aspects of eukaryotic cell
      function. The interphase microtubule network is essential for intracellular
      transport, organization, and cell polarization, whereas the mitotic spindle is
      required for chromosome segregation and cell division. Studies in different areas
      such as cell migration, mitosis, and asymmetric cell division have shown that
      Ran, Rho, and heterotrimeric G proteins regulate many aspects of microtubule
      functions. This review surveys how G protein-signaling coordinates microtubule
      polymerization and organization with specific cellular activities.

PMID- 15473865
TI  - Ribosomal protein S2 is a substrate for mammalian PRMT3 (protein arginine
      methyltransferase 3).
AB  - PRMT3 (protein arginine methyltransferase 3) is one of four type I arginine
      methyltransferases that catalyse the formation of asymmetric dimethylarginine.
      PRMT3 is unique in that its N-terminus harbours a C2H2 zinc-finger domain that is
      proposed to confer substrate specificity. In addition, PRMT3 is the only type I
      enzyme that is restricted to the cytoplasm. Known in vitro substrates for PRMT3
      include GST-GAR (a glutathione S-transferase fusion protein containing the
      glycine- and arginine-rich N-terminal region of fibrillarin), Sam68 (Src
      associated substrate during mitosis 68 kDa) and PABP-N1 [poly(A)-binding protein
      N1; PABP2]. Here we report the identification of an in vivo substrate for
      mammalian PRMT3. We found that FLAG-tagged PRMT3 can 'pull down' a protein with a
      molecular mass of 30 kDa from HeLa cell extracts. MS identified this PRMT3
      interacting protein as rpS2 (ribosomal protein S2). In vitro studies showed that
      the zinc-finger domain of PRMT3 is necessary and sufficient for binding to rpS2.
      In addition, rpS2 is methylated by PRMT3 in vitro and is also methylated in cell
      lines. Deletion analysis of the rpS2 amino acid sequence identified a N-terminal
      Arg-Gly repeat as the methylation site. Furthermore, both PRMT3 and rpS2 co
      sediment with free ribosomal subunits. These studies implicate PRMT3 in ribosomal
      function and in the regulation of protein synthesis.

PMID- 15473864
TI  - Hepatic farnesyl diphosphate synthase expression is suppressed by polyunsaturated
      fatty acids.
AB  - Dietary vegetable oils and fish oils rich in PUFA (polyunsaturated fatty acids)
      exert hypocholesterolaemic and hypotriglyceridaemic effects in rodents. The
      plasma cholesterol-lowering properties of PUFA are due partly to a diminution of
      cholesterol synthesis and of the activity of the rate-limiting enzyme HMG-CoA
      reductase (3-hydroxy-3-methylglutaryl-CoA reductase). To better understand the
      mechanisms involved, we examined how tuna fish oil and individual n-3 and n-6
      PUFA affect the expression of hepatic FPP synthase (farnesyl diphosphate
      synthase), a SREBP (sterol regulatory element-binding protein) target enzyme that
      is subject to negative-feedback regulation by sterols, in co-ordination with HMG
      CoA reductase. Feeding mice on a tuna fish oil diet for 2 weeks decreased serum
      cholesterol and triacylglycerol levels, by 50% and 60% respectively. Hepatic
      levels of FPP synthase and HMG-CoA reductase mRNAs were also decreased, by 70%
      and 40% respectively. Individual n-3 and n-6 PUFA lowered FPP synthase and HMG
      CoA reductase mRNA levels in H4IIEC3 rat hepatoma cells to a greater extent than
      did stearate and oleate, with the largest inhibitory effects occurring with
      arachidonate, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). We
      observed a similar inhibitory effect on protein levels of FPP synthase. The
      suppressive effect of PUFA on the FPP synthase mRNA level was not due to a
      decrease in mRNA stability, but to transcription inhibition. Moreover, a lower
      nuclear availability of both SREBP-1 and SREBP-2 mature forms was observed in
      HepG2 human hepatoblastoma cells treated with arachidonate, EPA or DHA. Taken
      together, these data suggest that PUFA can down-regulate hepatic cholesterol
      synthesis through inhibition of HMG-CoA reductase and FPP synthase, at least in
      part through impairment of the SREBP pathway.

PMID- 15473866
TI  - Compartmentalization of transport and phosphorylation of glucose in a hepatoma
      cell line.
AB  - The first steps of glucose metabolism are carried out by members of the families
      of GLUTs (glucose transporters) and HKs (hexokinases). Previous experiments using
      the inhibitor of glucose transport, CB (cytochalasin B), revealed that
      compartmentalization of GLUTs and HKs is a major factor in the control of glucose
      uptake in L6 myotubes [Whitesell, Ardehali, Printz, Beechem, Knobel, Piston,
      Granner, Van Der Meer, Perriott and May (2003) Biochem. J. 370, 47-56]. In the
      present paper, we evaluate compartmentalization of GLUTs and HKs in a hepatoma
      cell line, H4IIE, which is characterized by excess GLUT activity, HKI in a
      particulate and a cytosolic fraction, and insignificant G6Pase (glucose-6
      phosphatase) activity. The measured activity of glucose transport exceeded the
      rate of phosphorylation approx. 30-fold. Treatment with 25 microM CB (K(i)
      approximately 3 microM in H4IIE cells) paradoxically increased the excess of
      GLUTs over phosphorylation (GLUTs are inhibited 80%, while phosphorylation is
      inhibited 98%). The global relationships of the data could be reconciled most
      simply by a two-compartment model. In this model, phosphorylation of glucose is
      carried out by a subset of HK molecules supplied by a subset of GLUTs that are
      more sensitive to CB than the other GLUTs. The agent, DCC (dicyclohexylcarbodi
      imide) caused HKI to translocate from the particulate compartment to the
      cytosolic compartment and potently inhibited glucose phosphorylation. The
      particulate compartment may represent the mitochondria, to which the more CB
      sensitive GLUTs may control the transport of glucose.

PMID- 15473867
TI  - Isoprenoid biosynthesis as a target for antibacterial and antiparasitic drugs:
      phosphonohydroxamic acids as inhibitors of deoxyxylulose phosphate reducto
      isomerase.
AB  - Isoprenoid biosynthesis via the methylerythritol phosphate pathway is a target
      against pathogenic bacteria and the malaria parasite Plasmodium falciparum. 4
      (Hydroxyamino)-4-oxobutylphosphonic acid and 4-[hydroxy(methyl)amino]-4-oxobutyl
      phosphonic acid, two novel inhibitors of DXR (1-deoxy-D-xylulose 5-phosphate
      reducto-isomerase), the second enzyme of the pathway, have been synthesized and
      compared with fosmidomycin, the best known inhibitor of this enzyme. The latter
      phosphonohydroxamic acid showed a high inhibitory activity towards DXR, much like
      fosmidomycin, as well as significant antibacterial activity against Escherichia
      coli in tests on Petri dishes.

PMID- 15473869
TI  - Cellular immune responses in autoimmune thyroid disease.
AB  - Recent research in autoimmune thyroid disease (AITD) has largely focused on
      delineation of the autoantigens and their epitopes, but there is now renewed
      interest in the immunoregulatory properties of T cells, an understanding of which
      may explain the emergence of AITD in experimental settings. T cell recognition of
      autoantigens has shown considerable intra- and interindividual heterogeneity, and
      a mixed pattern of cytokine production indicates that both the Th1 and Th2 limbs
      of the helper T cell response are involved in all types of AITD. It is now clear
      that secretion of chemokines and cytokines within the thyroid accounts for the
      accumulation and expansion of the intrathyroidal lymphocyte pool, and that the
      thyroid cells themselves contribute to this secretion. The thyroid cells also
      produce a number of proinflammatory molecules which will tend to exacerbate the
      autoimmune process. Thyroid cell destruction in autoimmune hypothyroidism is
      dependent on T cell-mediated cytotoxicity with the likely additional effect of
      death receptor-mediated apoptosis.

PMID- 15473868
TI  - Proteasome-mediated effects on amyloid precursor protein processing at the gamma
      secretase site.
AB  - Abeta (beta-amyloid) peptides are found aggregated in the cortical amyloid
      plaques associated with Alzheimer's disease neuropathology. Inhibition of the
      proteasome alters the amount of Abeta produced from APP (amyloid precursor
      protein) by various cell lines in vitro. Proteasome activity is altered during
      aging, a major risk factor for Alzheimer's disease. In the present study, a human
      neuroblastoma cell line expressing the C-terminal 100 residues of APP (SH-SY5Y
      SPA4CT) was used to determine the effect of proteasome inhibition, by lactacystin
      and Bz-LLL-COCHO (benzoyl-Leu-Leu-Leu-glyoxal), on APP processing at the gamma
      secretase site. Proteasome inhibition caused a significant increase in Abeta
      peptide levels in medium conditioned by SH-SY5Y-SPA4CT cells, and was also
      associated with increased cell death. APP is a substrate of the apoptosis
      associated caspase 3 protease, and we therefore investigated whether the
      increased Abeta levels could reflect caspase activation. We report that caspase
      activation was not required for proteasome-inhibitor-mediated effects on APP
      (SPA4CT) processing. Cleavage of Ac-DEVD-AMC (N-acetyl-Asp-Glu-Val-Asp-7-amino-4
      methylcoumarin), a caspase substrate, was reduced following exposure of SH-SY5Y
      SPA4CT cells to lactacystin, and co-treatment of cells with lactacystin and a
      caspase inhibitor [Z-DEVD-FMK (benzyloxycarbonyl-Val-Ala-DL-Asp
      fluoromethylketone)] resulted in higher Abeta levels in medium, augmenting those
      seen with lactacystin alone. This study indicated that proteasome inhibition
      could increase APP processing specifically at the gamma-secretase site, and
      increase release of Abeta, in the absence of caspase activation. This indicates
      that the decline in proteasome function associated with aging would contribute to
      increased Abeta levels.

PMID- 15473870
TI  - Autoantibodies against the FSH receptor: association or causation?

PMID- 15473871
TI  - Abundance of adiponectin in the newborn.

PMID- 15473872
TI  - Plasma adiponectin levels in newborns are higher than those in adults and
      positively correlated with birth weight.
AB  - OBJECTIVE: The aim of this study was to examine plasma adiponectin concentrations
      during perinatal the period and their correlations with fetal anthropometric
      parameters and other hormones. DESIGN: Venous cord blood samples were obtained
      from 59 full-term healthy newborns (36 males and 23 females, gestational age 37.0
      41.4 weeks, birth weight 2,146-4,326 g, birth length 44.0-54.5 cm). The blood
      samples were also obtained from 15 neonates (postnatal day 3-7) whose cord blood
      had already been collected and the changes in adiponectin concentrations were
      examined. MEASUREMENTS: The adiponectin concentration was determined by enzyme
      linked immunosorbent assay. The leptin concentration was determined by
      radioimmunoassay. Insulin, GH and IGF-1 concentrations were determined by
      immunoradiometric assays. RESULTS: The plasma adiponectin concentrations in cord
      blood ranged from 6.0 to 55.8 microg/ml (median 22.4 microg/ml), which were much
      higher than those in normal-weight adults (P < 0.0001). In contrast to the
      findings in adults, these values were positively correlated with birth weight (r
      = 0.43, P = 0.0005), body mass index (r = 0.44, P = 0.0005), birth weight/birth
      length ratio (r = 0.46, P = 0.0002) and the leptin concentrations (r = 0.39, P =
      0.004). When the effects of fat mass-related anthropometric parameters such as
      the birth weight/birth length ratio were controlled, plasma adiponectin
      concentrations had a significant inverse correlation with insulin concentrations
      (r = -0.35, P = 0.01). There was no significant gender difference in adiponectin
      concentrations among newborns. The adiponectin concentrations in neonates
      (postnatal day 3-7) did not change significantly compared with those in cord
      blood. CONCLUSIONS: In contrast to the findings in adults, these results suggest
      that the adiponectin concentration increases with the mass of fetal fat.

PMID- 15473873
TI  - Abnormalities of proinsulin processing in functioning insulinomas: clinical
      implications.
AB  - OBJECTIVE: Abnormal proinsulin processing in insulinomas may result in secretory
      granules containing both insulin and proinsulin, a finding not encountered in
      healthy beta-cells. The aim of this study was to test whether such abnormalities
      in the proinsulin to insulin conversion have clinical implications in patients
      with hypoglycaemic disorders. DESIGN: Case-series. PATIENTS AND METHODS: Fifteen
      patients with histologically confirmed insulinoma and two patients with islet
      cell hyperplasia were included. The immunohistochemical distribution pattern of
      proinsulin within the tumour cells was classified as Golgi pattern (predominantly
      perinuclear immunolabelling) or diffuse pattern (immunolabelling in the periphery
      of the cells, indicating the presence of proinsulin in secretory granules). Data
      obtained from the 72-h fast and arterial calcium stimulation and hepatic venous
      sampling (ASVS) test were related to the morphological classification. RESULTS:
      Six insulinomas exhibited a diffuse proinsulin distribution pattern, while nine
      insulinomas and two islet cell hyperplasias disclosed a Golgi pattern. Median
      proinsulin concentrations at the termination of the fast tended to be higher in
      patients with the diffuse proinsulin distribution pattern than in patients with
      the Golgi pattern (86.9 vs. 18.8 pmol/l, P = 0.07). Higher insulin (P < 0.005)
      and proinsulin (P < 0.05) concentrations were significantly correlated with
      earlier occurrence of hypoglycaemia during the prolonged fast. During the ASVS
      test, tumours with the diffuse proinsulin distribution pattern exhibited a higher
      increase in both insulin (median, 37.3- vs. 10.5-fold, P < 0.05) and proinsulin
      (6.3- vs. 1.6 fold, P < 0.005) concentrations following calcium stimulation than
      the tumours with the Golgi pattern. CONCLUSIONS: Abnormalities in the proinsulin
      to insulin conversion in patients with insulinomas and islet cell hyperplasia
      correlate with impaired regulation of both insulin and proinsulin secretion
      during the prolonged fast as well as the ASVS test.

PMID- 15473874
TI  - Inhibition of endothelial proliferation by the somatostatin analogue SOM230.
AB  - OBJECTIVE: Somatostatin (SST) modulates exocrine and endocrine secretion,
      proliferation and apoptosis via five G protein-linked receptors (SSTRs 1-5). Long
      acting SST analogues such as Octreotide, and the new analogue SOM230, have been
      developed for the treatment of neuroendocrine tumours. Octreotide has previously
      been reported to inhibit endothelial proliferation. We wished to determine if
      SOM230 is a more potent inhibitor of endothelial cell proliferation than
      Octreotide. DESIGN: We have determined the expression of SSTRs in proliferating
      human umbilical vein endothelial cells (HUVECs) in vitro, and determined their
      response to the somatostatin analogues SOM230 and Octreotide, following vascular
      endothelial growth factor (VEGF) stimulation. MEASUREMENTS: Quantitative RT-PCR
      and western blotting were used to determine the expression of SSTRs 1-5 in
      proliferating HUVECs. These cells were grown in media containing 200 pg/ml VEGF
      and treated with 10(-11) to 10(-6) M Octreotide or SOM230. The WST-1 assay was
      then used to determine the effects of these analogues on HUVEC proliferation.
      RESULTS: Using quantitative RT-PCR and western blotting, HUVECs were found to
      express SSTRs 1, 2 and 5. SSTRs 3 and 4 were not detected. Using the WST-1 assay,
      SOM230 was found to significantly inhibit proliferation by up to 46.0% +/- 9.4%
      (10(-6)-10(-7) M; P < 0.05), whereas in parallel studies Octreotide failed to
      inhibit HUVEC proliferation. CONCLUSIONS: The pan SST analogue SOM230 inhibits
      proliferation of HUVECs, which are unaffected by Octreotide. SOM230 may thus
      represent a suitable candidate drug for antiangiogenic therapy.

PMID- 15473875
TI  - Growth hormone (GH)-induced reconstitution of CD8+ CD28+ T lymphocytes in a rare
      case of severe lymphopenia associated with Juvenile Haemochromatosis and Turner's
      syndrome.
AB  - This paper describes a rare case of Turner's syndrome associated with Juvenile
      Haemochromatosis and severe lymphopenia, followed-up for a period of 5 years.
      Because of the indication for treatment with growth hormone (GH), this case was
      observed as a model to analyse the effects of GH on growth, iron mobilization and
      lymphocyte reconstitution. For this purpose, a serial study of the T lymphocyte
      subpopulations CD4+, CD8+, CD8+ CD28+ and CD8+ CD28- was performed by
      immunophenotyping during the follow-up period. Besides the impact of both
      phlebotomy treatment and GH on the rapid growth and mobilization of 20.8 g of
      iron in 136 weeks, the most relevant observation was the finding of a significant
      expansion of CD8+ T lymphocytes expressing the costimulatory marker CD28 in the
      setting of the severe lymphopenia. These findings constitute new clinical
      evidence supporting the notion that the GH/IGF-1 system has an important role on
      the maintenance of T cell homeostasis in vivo, and that GH may be regarded as a
      putative therapeutic agent in T lymphocyte reconstitution.

PMID- 15473876
TI  - Children with congenital hypothyroidism are at risk of adult obesity due to early
      adiposity rebound.
AB  - OBJECTIVE: There is some evidence that children with congenital hypothyroidism
      (CH) are heavier than their reference population. There are few data on adults
      with CH. The timing of adiposity rebound (AR) in childhood has been shown to have
      strong correlations with adult obesity. Our aims were to study the timing of AR
      and factors affecting AR in children with CH. PATIENTS AND METHODS: The timing of
      AR was examined in a retrospective study of children with CH with growth data at
      least up to 5 years of age. The proportion of children with CH who reached AR by
      37 months and by 49 months of age were compared with healthy children and
      children with acute lymphoblastic leukaemia (ALL) described in the literature.
      Correlation of timing of AR with body mass index (BMI) standard deviation score
      (SDS) at 10 years, initial severity of hypothyroidism and age at normalization of
      TSH were examined. Multiple logistic regression was used to identify independent
      factors associated with BMI > or = 20 (overweight) at 10 years of age. RESULTS:
      The study included 53 children (34 females and 19 males). AR had occurred by 37
      months in 37.7% children with CH, in 42.7% children treated for ALL (CH vs. ALL,
      P = 0.58) and in 4.5% healthy British children (CH vs. normal, P < 0.0001). We
      found that 54.7% children with CH had reached AR compared with 21.4% of normal
      children (CH vs. normal, P < 0.0001) by the age of 49 months. Timing of AR showed
      significant negative correlation with BMI SDS at 10 years (r = -0.487, P = 0.01).
      There were no significant relationships between timing of AR and initial thyroid
      function or age at normalization of TSH. Multiple logistic regression analysis
      identified age at AR as an independent factor associated with BMI > or = 20 at 10
      years of age (P = 0.04). CONCLUSIONS: Children with CH showed significantly
      earlier AR compared to normal British children. This showed significant negative
      correlation with BMI SDS at 10 years. AR in CH does not appear to be directly
      related to the initial severity of hypothyroidism or to treatment factors.

PMID- 15473877
TI  - Assessment of the role of 17beta-oestradiol in bone metabolism in men: does the
      assay technique matter? The MINOS study.
AB  - OBJECTIVE: 17Beta-oestradiol (17beta-E2), mainly its bioavailable fraction (bio
      17beta-E2), is a determinant of bone mineral density (BMD) and bone remodelling
      in men. As direct measurement of bio-17beta-E2 is time-consuming, we compared the
      value of directly measured bio-17beta-E2 and of calculated bio-17beta-E2 and free
      17beta-E2 by studying their association with BMD and markers of bone turnover in
      a cohort of men (MINOS). DESIGN: A cross-sectional study in which the association
      between BMD and bone markers, on the one hand, and serum levels of 17beta-E2, on
      the other, was analysed according to the levels of measured and calculated bio
      17beta-E2 and free 17beta-E2 in a cohort of men. SUBJECTS: Men from the MINOS
      cohort including 87 men aged 19-45 to establish the reference control normal
      range of hormones and 637 men aged 50-85 (studied group). MEASUREMENTS: Total
      17beta-E2, testosterone, SHBG and albumin were measured by standard methods. bio
      17beta-E2 was directly measured after the precipitation of SHBG by ammonium
      sulfate. bio-17beta-E2 and free 17beta-E2 were calculated using serum SHBG and
      albumin levels as described by Sodegard et al. (J. Steroid Biochem., 16 (1982)
      801). RESULTS: Calculated bio-17beta-E2 and free 17beta-E2 were correlated with
      measured bio-17beta-E2 and between themselves (r = 0.90-1.00, P < 0.0001).
      Calculated bio-17beta-E2 and free 17beta-E2 disclosed a similar association with
      BMD (difference between lowest and highest quartiles of 17beta-E2: 2.6-6.8%, P <
      0.05-0.005) to that of measured bio-17beta-E2 (3.6-6.1%, P < 0.005-0.001). The
      association between bone markers levels and measured vs. calculated 17beta-E2
      were also similar. Predictive accuracy for lowered BMD and elevated levels of
      biochemical bone markers (evaluated using receiver operating characteristics) was
      relatively low (area under curve -0.582 to 0.709) but similar for different forms
      of bioavailable and free 17beta-E2. CONCLUSIONS: In elderly men, the
      concentrations of bioavailable and free 17beta-E2, calculated using equations
      including either the measured albumin concentration or the constant albumin
      concentration of 43 g/l, can be used, at least in clinical studies, instead of
      the bio-17beta-E2 concentrations measured after ammonium sulfate precipitation.

PMID- 15473878
TI  - Long-term negative impact on quality of life in patients with successfully
      treated Cushing's disease.
AB  - OBJECTIVE: A cohort of pituitary tumour patients, who had undergone definitive
      treatment within a 15-year period at a single neuroscience centre, were
      investigated as to whether there were differences in psychological well-being and
      psychosocial functioning, dependent on endocrine pathology and treatment
      variables. DESIGN: A detailed assessment of 114 patients with benign pituitary
      tumours in relation to primary diagnosis and mode of treatment was carried out.
      Psychological rating scales used were: the Hospital Anxiety and Depression Scale-
      UK version (HADS-UK), the World Health Organization Quality of Life Scale-
      abbreviated version (WHOQOL-BREF), General Health Questionnaire 28 (GHQ-28), the
      Functional Assessment of Cancer Therapy (FACT) and the Social Adjustment Scale-
      modified (SAS1 and SAS2; the former completed by the patient and the latter by
      another person who knows the patient well). All Cushing's patients were
      biochemically cured as defined by a normal 24-h urine free cortisol excretion
      within the previous 6 months. RESULTS: Patients with treated Cushing's disease
      had significantly impaired psychological well-being and psychosocial functioning
      across all tested domains compared with all other pituitary tumours, where scores
      were similar. When participants with Cushing's disease were excluded, patients
      who had undergone transfrontal surgery scored significantly higher on GHQ and
      HADS ratings than transsphenoidally treated patients. CONCLUSION: Cushing's
      disease even when biochemically stable has long-term adverse effects on mood and
      social functioning. We hypothesize that this may be related to irreversible
      changes in central neural function. Further studies are necessary to define the
      precise pathways involved.

PMID- 15473879
TI  - Bone mineral density in hyperthyroidism.
AB  - OBJECTIVE: To investigate whether previous hyperthyroidism is a cause of
      permanent secondary osteoporosis. DESIGN AND PATIENTS: In this cross-sectional
      study, 164 women with untreated or previously treated overt and symptomatic
      hyperthyroidism were examined 0-31 years after the initial episode of
      hyperthyroidism and its treatment, and were compared with a control group of 79
      age-matched women without previous history of hyperthyroidism. Subjects with
      current or previous metabolic bone disease, any antiresorptive treatment for
      osteoporosis or treatments and habits known to affect bone metabolism were
      excluded. MEASUREMENTS: The age of the first manifestation of the disease, the
      age at the measurement of bone mineral density (BMD) at the spine and femoral
      neck and the interval between diagnosis and treatment of hyperthyroidism and BMD
      measurement were recorded and the Z-scores and T-scores of BMD were analysed.
      RESULTS: Untreated hyperthyroidism and hyperthyroidism up to 3 years after its
      diagnosis and treatment were associated with decreased BMD. Three or more years
      after the first episode of the disease the mean Z-score at both skeletal sites
      was near zero and not different from the controls. The age at which
      hyperthyroidism was manifested for the first time had no effect on the final
      outcome. Women affected at a young age (13-30 years) had a more pronounced loss
      of BMD when examined untreated or early (< 3 years) after diagnosis, but a BMD
      significantly above zero if examined later (> 3 years). Older women (aged 51-70
      years) showed a similar pattern, although the differences were not significant.
      Middle-aged subjects (31-50 years) had the smallest loss of BMD during the first
      3 years. Analysis of T-scores of former hyperthyroid women aged > or = 51 years
      showed no significantly different relative risk (RR) for osteoporosis in
      comparison with the controls. However, the study was not powered enough to give
      meaningful RR results. CONCLUSIONS: Overt symptomatic hyperthyroidism is
      associated with decreased BMD during the first 3 years after diagnosis and
      treatment of the disease. After this interval, former hyperthyroid women have a Z
      score near zero and not different from women without a history of the disease,
      apparently because of recovery of the bone density lost early during the course
      of the disease. Symptomatic hyperthyroidism does not seem to be a cause of long
      lasting osteoporosis, and the age of the patient during the first episode is
      irrelevant.

PMID- 15473880
TI  - Insulin sensitivity in growth hormone-deficient children: influence of
      replacement treatment.
AB  - OBJECTIVE: In adults, excessive GH secretion may lead to secondary diabetes
      mellitus, while prolonged GH treatment may accelerate the onset of type 2
      diabetes mellitus in predisposed children. The aim of the study was to evaluate
      insulin sensitivity (IS) and glucose tolerance (GT) in a group of GH-deficient
      children treated with GH for a period of 6 years. PATIENTS AND DESIGN: One
      hundred and twenty-eight children (40 females, 88 males) were included in the
      study. At the beginning of treatment chronological age was 8.9 +/- 3.2 years,
      height standard deviation score (SDS) -2.43 +/- 0.90 and body mass index (BMI)
      SDS 0.18 +/- 1.60. At the end of the study chronological age was 13.0 +/- 2.9
      years, height SDS -1.24 +/- 1.27 and BMI SDS 0.23 +/- 1.54. GH was administered
      at a mean weekly dosage of 0.3 mg/kg, injected subcutaneously over 6-7 days. GT
      was assessed according to the criteria of the Expert Committee on the Diagnosis
      and Classification of Diabetes Mellitus. IS was evaluated with the quantitative
      insulin sensitivity check index (QUICKI). RESULTS: No cases of impaired GT or
      diabetes were recorded during the follow-up period. IS, already lower than in
      controls before starting treatment with GH, decreased significantly during the
      first year of therapy (QUICKI: 0.346 +/- 0.033 vs. 0.355 +/- 0.044, P < 0.05),
      with no further decrease in the following years. No correlation was found between
      QUICKI, BMI, years of treatment and onset of puberty. CONCLUSIONS: GH treatment
      in GH-deficient children does not lead to an impaired GT or type 2 diabetes
      mellitus, although it does significantly decrease IS.

PMID- 15473881
TI  - Cavernous and inferior petrosal sinus sampling in the evaluation of ACTH
      dependent Cushing's syndrome.
AB  - OBJECTIVE: Central venous sampling (CVS) is used frequently in the evaluation of
      ACTH-dependent Cushing's syndrome. However, several controversies exist including
      the diagnostic accuracy, the sampling site of choice (cavernous sinus vs.
      inferior petrosal sinus) and the use of lateralization data in tumour
      localization. We have analysed our experience with CVS to address these
      controversies. DESIGN: We retrospectively reviewed CVS data in patients with ACTH
      dependent Cushing's syndrome, in whom cavernous sinus sampling (CSS), inferior
      petrosal sinus sampling (IPSS) and IPSS after administration of ovine
      corticotrophin releasing hormone (oCRH) were performed. PATIENTS: Data on 95
      patients were analysed, including 79 patients with suspected Cushing's disease
      (CD) and 16 patients with suspected ectopic ACTH syndrome (EAS). RESULTS: For the
      differential diagnosis of ACTH-dependent Cushing's syndrome, the diagnostic
      accuracy of IPSS after oCRH stimulation was 97% compared to 86% for CSS. While no
      single sampling site was perfect in diagnostic accuracy, sampling both CS and IPS
      achieved a combined diagnostic accuracy of 100%. Lateralization data predicted
      tumour location in 62-68% of the patients with various central venous drainage
      patterns and in 77-80% of the patients with symmetrical drainage. CSS was not
      significantly superior to IPSS in tumour lateralization. In patients with
      suspected CD based on CVS and in whom an adenoma was not found on magnetic
      resonance imaging (MRI) and not located by the surgeon intraoperatively,
      hemihypophysectomy based on lateralization data was successful in only 10 of the
      18 patients (56%) with various central venous drainage patterns and in 5 of 10
      patients with symmetrical drainage. CONCLUSION: CVS is a powerful method for
      differentiating CD from the EAS. CSS without oCRH was not superior to IPSS after
      oCRH stimulation; however, we achieved a 100% diagnostic accuracy if at least two
      sites were sampled. Tumour localization by CVS did not accurately predict the
      tumour site at surgery and should not be used to guide surgical resection.

PMID- 15473882
TI  - Combined evaluation of resting IGF-I, N-terminal propeptide of type III
      procollagen (PIIINP) and C-terminal cross-linked telopeptide of type I collagen
      (ICTP) levels might be useful for detecting inappropriate GH administration in
      athletes: a preliminary report.
AB  - OBJECTIVE: To verify whether combined measurements of GH-dependent parameters
      might be useful in detecting exogenous recombinant GH (rGH) administration in
      male athletes from different disciplines. METHODS: Sixty-six athletes (control
      group) were sampled for the evaluation of resting IGF-I, N-terminal propeptide of
      type III procollagen (PIIINP) and telopeptide type I collagen (ICTP). Cut-off
      values (mean + 2 SD) for IGF-I, PIIINP and ICTP were calculated and arbitrary
      scores (1.5, 2.0) were assigned to abnormal parameters. By using the sum of
      individual parameter scores, positive (> or = 3) or negative (< 3) scores were
      obtained. In addition, a subgroup of six athletes was treated for 3 weeks with
      rGH (0.09 IU/kg body weight, 6 days/week) and was similarly evaluated at the end
      of the 1st, 2nd and 3rd week (i.e. 18 samples). RESULTS: Abnormal IGF-I, or
      PIIINP or ICTP levels were found, respectively, in one, two and four subjects
      (1.5-6.1%) of the control group (in the younger athletes); only one 19-year-old
      subject of this group obtained a positive score. Abnormal IGF-I, PIIINP and ICTP
      levels were found in 61.1-66.7% samples of the treated group. Positive cases were
      3/6 at the 1st and 2nd week and 6/6 at the 3rd week. The sensitivity of the
      screening approach was 50-100% (at the 1st-2nd and 3rd week, respectively) and
      specificity was 98.5%. CONCLUSION: This 'first level' screening test is safe,
      acceptable and relatively inexpensive. Further additional investigations of
      'second level' (i.e. GH secretory profile, GH response to a GH-releasing peptide)
      can be retained to validate or exclude rGH administration or for the early
      diagnosis of infrequent endogenous GH hypersecretion.

PMID- 15473883
TI  - Diagnosis and management of amiodarone-induced thyrotoxicosis in Europe: results
      of an international survey among members of the European Thyroid Association.
AB  - OBJECTIVE: To determine how expert European thyroidologists assess and treat
      amiodarone-induced thyrotoxicosis (AIT). DESIGN: Members of the European Thyroid
      Association (ETA) with clinical interests were asked to answer a questionnaire on
      the diagnosis and management of AIT. A total of 124 responses were received: 116
      from Europe, seven from USA and one from Brazil. After excluding responses coming
      from the same centre, 101 responses from 24 European countries were analysed,
      representing approximately 65% of clinically active European ETA members.
      RESULTS: The majority of respondents (68%) see 1-10 new cases of AIT/year, and
      AIT seems to be more frequent than amiodarone-induced hypothyroidism in Europe,
      where in many instances iodine intake is borderline or moderately deficient. A
      good collaboration with cardiologists exists in most centres, and patients
      receiving chronic amiodarone treatment are checked for thyroid function most
      commonly every 4-6 months. When AIT is suspected, a diffuse or nodular goitre is
      present or in the absence of apparent abnormalities of the thyroid, free
      thyroxine (FT4), free triiodothyronine (FT3) and TSH are assayed by almost 90% of
      respondents. Thyroid autoimmunity is evaluated in the initial assessment by >
      80%, while evaluation of urinary iodine excretion is unhelpful for > 60%. Most
      commonly used additional diagnostic procedures include thyroid ultrasonography,
      particularly colour flow Doppler sonography, and, to a lesser extent, a thyroid
      uptake scan. If the thyroid gland is apparently normal, measurement of thyroidal
      radioactive iodine uptake is considered useful by a large proportion of
      respondents to establish the destructive nature of the process. Differentiation
      of type I and type II AIT is difficult and, possibly, not correct for 27% of
      respondents, who believe that mixed (or indefinite) forms are probably more
      frequent than previously recognized. Approximately 10-20% do not consider
      amiodarone withdrawal necessary in the therapeutic strategy of AIT, especially if
      the thyroid gland is apparently normal. Most respondents (82%) treat type I AIT
      with thionamides, either alone (51%) or in combination with potassium perchlorate
      (31%), while the preferred treatment for type II AIT is represented by
      glucocorticoids (46%). Some respondents, in view of diagnostic difficulties,
      initially treat all cases of AIT with a combination of thionamides and
      glucocorticoids. After restoration of euthyroidism, ablative therapy is
      recommended by 34% in type I and only 8% in type II AIT. If amiodarone therapy
      needs to be reinstituted, prophylactic thyroid ablation is recommended by 65% in
      type I AIT, while a wait-and-see strategy is adopted by 70% in type II AIT.
      CONCLUSION: Areas of certainty and uncertainty concerning AIT are present among
      expert European thyroidologists, both from a diagnostic and a therapeutic
      standpoint. Diagnostic criteria need to be refined in order to improve
      therapeutic outcome.

PMID- 15473884
TI  - Ghrelin secretion is inhibited by glucose load and insulin-induced hypoglycaemia
      but unaffected by glucagon and arginine in humans.
AB  - OBJECTIVE: Circulating ghrelin levels are increased by fasting and decreased by
      feeding, glucose load, insulin and somatostatin. Whether hyperglycaemia and
      insulin directly inhibit ghrelin secretion still remains matter of debate. The
      aim of the present study was therefore to investigate further the regulatory
      effects of glucose and insulin on ghrelin secretion. DESIGN AND SUBJECTS: We
      studied the effects of glucose [oral glucose tolerance test (OGTT) 100 g orally],
      insulin-induced hypoglycaemia [ITT, 0.1 IU/kg insulin intravenously (i.v.)],
      glucagon (1 mg i.v.), arginine (0.5 mg/kg i.v.) and saline on ghrelin, GH,
      insulin, glucose and glucagon levels in six normal subjects. MEASUREMENTS: In all
      the sessions, blood samples were collected every 15 min from 0 up to + 120 min.
      Ghrelin, GH, insulin, glucagon and glucose levels were assayed at each time
      point. RESULTS: OGTT increased (P < 0.01) glucose and insulin while decreasing (P
      < 0.01) GH and ghrelin levels. ITT increased (P < 0.01) GH but decreased (P <
      0.01) ghrelin levels. Glucagon increased (P < 0.01) glucose and insulin without
      modifying GH and ghrelin. Arginine increased (P < 0.01) GH, insulin, glucagon and
      glucose (P < 0.05) but did not affect ghrelin secretion. CONCLUSIONS: Ghrelin
      secretion in humans is inhibited by OGTT-induced hyperglycaemia and ITT but not
      by glucagon and arginine, two substances able to increase insulin and glucose
      levels. These findings question the assumption that glucose and insulin directly
      regulate ghrelin secretion. On the other hand, ghrelin secretion is not
      associated with the GH response to ITT or arginine, indicating that the
      somatotroph response to these stimuli is unlikely to be mediated by ghrelin.

PMID- 15473885
TI  - K40E: a novel succinate dehydrogenase (SDH)B mutation causing familial
      phaeochromocytoma and paraganglioma.
AB  - OBJECTIVE: Germline mutations in succinate dehydrogenase (SDH)B, SDHC and SDHD,
      encoding three of the four subunits of mitochondrial complex II, have been
      implicated in the tumourigenesis of familial paragangliomas and
      phaeochromocytomas. Twenty-three SDHB mutations have been identified to date.
      PATIENTS: We present a novel missense SDHB exon 2 mutation (c.118 A > G; K40E)
      identified in an Australian family. The proband was diagnosed with
      phaeochromocytoma at an early age following an unexpected hypertensive crisis and
      was found to be SDHB mutation-positive. Subsequent genetic screening of 26 family
      members has identified 17 mutation-positive relatives. In addition to the
      proband, four mutation positive relatives were found to have clinical symptoms or
      a lesion and/or catecholamine excess after the identification of the mutation led
      to further evaluation. Both the proband and an uncle have required surgical
      removal of a tumour. CONCLUSIONS: This family indicates the importance of
      germline screening of first-degree relatives when a patient presents with an
      apparently sporadic extra adrenal phaeochromocytoma at a young age or whenever a
      patient with a nonsecretory paraganglioma is found.

PMID- 15473888
TI  - Aldosterone antagonism in heart failure: improvement of cardiac remodelling,
      endothelial dysfunction and platelet activation.

PMID- 15473886
TI  - Association of serum paraoxonase activity with insulin sensitivity and oxidative
      stress in hyperthyroid and TSH-suppressed nodular goitre patients.
AB  - OBJECTIVE: Low serum paraoxonase (PON) activity is thought to be a risk factor
      for the development of atherosclerosis. The present study was designed to
      evaluate PON1 activity and its relationship with preatherosclerotic markers such
      as lipid peroxidation and insulin resistance in hyperthyroid patients before and
      after propylthiouracil (PTU) treatment and in subjects with iatrogenic
      subclinical hyperthyroidism. PATIENTS AND DESIGN: Twenty patients with
      hyperthyroidism, 20 patients with euthyroid multinodular goiter (MNG) and 20 age-
      and sex-matched healthy controls were enrolled in the study. Insulin sensitivity
      index, PON activity and lipid peroxidation were measured at baseline and 2 months
      after achieving euthyroidism or subclinical hyperthyroidism. Levothyroxine was
      given as a part of TSH suppression therapy in multinodular goitre patients.
      MEASUREMENTS: Insulin sensitivity was determined by an oral glucose tolerance
      test (OGTT) based on the insulin sensitivity index (ISI) formula, serum
      paraoxonase activity was determined with a spectrophotometric method. Lipid
      peroxidation was measured by the formation of thiobarbituric acid reactive
      substances (TBARs). RESULTS: ISI was significantly lower in the hyperthyroid
      group than baseline levels in MNG patients and controls (P < 0.001). While ISI
      increased after treatment in the hyperthyroid group (P < 0.01), it significantly
      decreased with L-T4 treatment in the MNG group (P < 0.01). Serum paraoxonase
      activity was significantly lower in the hyperthyroid group before treatment than
      baseline and final measurements of other groups (P < 0.05). While PON activity
      increased after restoration of the euthyroid state in the hyperthyroid group (P <
      0.05), it decreased with L-T4 treatment in the MNG group (P < 0.05). Lipid
      peroxidation was significantly higher in hyperthyroid group compared to baseline
      levels of other groups (P < 0.05). It decreased after treatment in the
      hyperthyroid group (P < 0.05) but a significant increase was observed following L
      T4 treatment in the MNG group (P < 0.05). Serum paraoxonase activity was found to
      be negatively correlated with serum TT4 (r = -0.32, P = 0.003), TT3 levels (r = 
      0.31, P = 0.004), TBARs levels (r = 0.32, P = 0.003) and positively correlated
      with ISI (r = 0.35, P = 0.001) and high-density lipoprotein (HDL) cholesterol
      levels (r = 0.35, P = 0.0011) in the hyperthyroid and MNG groups. CONCLUSIONS:
      Iatrogenic thyroid hormone excess seems to mimic the effects of endogenous
      thyroid hormone excess on paraoxonase activity, insulin sensitivity and oxidative
      stress. These findings suggest that TSH suppression with levothyroxine may
      increase oxidative stress and LDL oxidation and thereby promote atherogenesis.

PMID- 15473889
TI  - Aldosterone: from integrative physiology to cellular biology and back.

PMID- 15473890
TI  - Cholesterol saturation rather than phospholipid/bile salt ratio or protein
      content affects crystallization sequences in human gallbladder bile.
AB  - BACKGROUND: In model biles, cholesterol crystallization (an important factor in
      gallstone formation) mainly depends on phospholipid/bile salt ratios with
      characteristic sequences of plate-like (monohydrate) vs. non-plate-like (presumed
      anhydrous: arcs, needles, tubules, spirals) cholesterol crystals. We now
      investigate whether the same phenomenon occurs in human bile. METHODS:
      Appearances of plate-like and non-plate-like cholesterol crystals were determined
      in filtered bile of 80 cholesterol gallstone patients, and related to biliary
      lipid and pro-nucleating protein composition. RESULTS: Non-plate-like crystals
      appeared before plate-like crystals in 9 biles, on the same day in 24 biles, and
      after plate-like crystals in 31 biles. In 16 biles only plate-like crystals were
      observed. Crystal sequences did not depend on biliary lipid or protein
      composition. Cholesterol saturation indexes were higher in biles with than
      without non-plate-like crystals (150 +/- 6 vs. 125 +/- 12, P = 0.02). In
      contrast, phospholipid/(bile salt + phospholipid) ratios, bile salt species,
      phospholipid classes, concentrations of mucin, IgG, IgM, IgA, haptoglobin and
      alpha-1 acid glycoprotein did not differ. CONCLUSIONS: Cholesterol
      crystallization sequences in human bile depend on cholesterol saturation index
      rather than on phospholipid/bile salt ratio.

PMID- 15473891
TI  - Insulin activates vascular endothelial growth factor in vascular smooth muscle
      cells: influence of nitric oxide and of insulin resistance.
AB  - BACKGROUND: We aimed to evaluate whether insulin influences vascular endothelial
      growth factor (VEGF) synthesis and secretion in cultured vascular smooth muscle
      cells (VSMCs) via nitric oxide (NO) and whether these putative effects are lost
      in insulin-resistant states. MATERIALS AND METHODS: In VSMC derived from human
      arterioles and from aortas of insulin-sensitive Zucker fa/+rats and insulin
      resistant Zucker fa/fa rats incubated with different concentrations of human
      regular insulin with or without inhibitors of phosphatidylinositol 4,5
      bisphosphate 3-kinase (PI3-K), mitogen-activated protein kinase (MAPK), nitric
      oxide synthase (NOS) and guanosine 3',5'cyclic monophosphate(cGMP)-dependent
      protein kinase (PKG), we measured protein expression (Western blot) and secretion
      (ELISA) of VEGF. RESULTS: We found that in VSMCs from humans and from insulin
      sensitive Zucker fa/+rats, insulin increases VEGF protein expression and
      secretion, with mechanisms blunted by wortmannin and LY294002 (PI3-K inhibitors),
      PD98059 (MAPK inhibitor), L-NMMA (NOS inhibitor) and Rp-8pCT-cGMPs (PKG
      inhibitor). Also the NO donor sodium nitroprusside (SNP) and the cGMP analogue 8
      Bromo-cGMP increase VEGF protein expression and secretion, with mechanisms
      inhibited by wortmannin and PD98059. The insulin effects on VEGF are impaired in
      VSMCs from Zucker fa/fa rats, which also present a reduced insulin ability to
      increase NO. CONCLUSIONS: In VSMCs from humans and insulin-sensitive Zucker
      fa/+rats: (i) insulin increases VEGF protein expression and secretion via both
      PI3-K and MAPK; (ii) the insulin effects on VEGF are mediated by nitric oxide.
      The insulin action on both nitric oxide and VEGF is impaired in VSMCs from Zucker
      fa/fa rats, an animal model of metabolic and vascular insulin-resistance.

PMID- 15473892
TI  - Novel therapeutic approach for cancer using four cardiovascular hormones.
AB  - BACKGROUND: The atrial natriuretic peptide (ANP) gene synthesizes four
      cardiovascular hormones, i.e. vessel dilator, long-acting natriuretic peptide,
      kaliuretic peptide and ANP, which decrease the number of human pancreatic
      adenocarcinoma cells in culture by 65%, 47%, 37%, and 34%, respectively. METHODS
      AND MATERIALS: None of the cardiovascular hormones has been investigated to
      determine whether they inhibit the growth of cancers in vivo. These four hormones
      were evaluated for their ability to inhibit the growth of human pancreatic
      adenocarcinomas in athymic mice. RESULTS: Vessel dilator (139 ng min(-1) kg(-1)
      of body weight) infused for 14 days completely stopped the growth of human
      pancreatic adenocarcinomas in athymic mice (n = 14) with a decrease in their
      tumour volume, while the tumour volume increased 69-fold (P < 0.001) in the
      placebo (n = 30)-treated mice. When these peptide hormones (each at 1.4 microg
      min(-1) kg(-1) body weight) were infused for 4 weeks, vessel dilator, long-acting
      natriuretic peptide and kaliuretic peptide decreased tumour volume after 1 week
      by 49%, 28%, and 11%, respectively, with a one- and 20-fold increase in the
      tumour volume in ANP- and placebo-treated mice. Cyclic GMP (2.4 microg min(-1)
      kg(-1) body weight) inhibited after 1 week the growth of this cancer 95%.
      CONCLUSIONS: These results suggest that these peptide hormones have useful
      anticancer properties, as they each inhibited the growth of the human pancreatic
      adenocarcinomas in vivo and three of the four peptide hormones decreased the
      volume of the tumours (up to 49%, i.e. vessel dilator). Part of their mechanism
      of action appears to be mediated by cyclic GMP.

PMID- 15473893
TI  - N-acetylcysteine enhances multidrug resistance-associated protein 1 mediated
      doxorubicin resistance.
AB  - BACKGROUND: Resistance of cancer cells against anticancer agents is caused partly
      by multidrug resistance-associated protein 1 (MRP1). The exact mechanism of MRP1
      involved multidrug resistance has not yet been clarified, although glutathione
      (GSH) is likely to have a role for the resistance to occur. N-acetylcysteine
      (NAC) is a pro-glutathione drug. DL-buthionine (S,R)-sulfoximine (BSO) inhibits
      GSH synthesis. The aim of our study was to investigate the effect of NAC and BSO
      on MRP1-mediated doxorubicin resistance in human embryonic kidney (HEK293) and
      its MRP1-transfected 293MRP cells. MATERIALS AND METHODS: Human embryonic kidney
      cells were transfected with a plasmid encoding the whole MRP1 gene. Both cells
      were incubated with doxorubicin in the presence or absence of NAC and/or BSO. The
      viability of both cells was determined under different incubation conditions.
      Glutathione, glutathione S-transferase (GST) and glutathione peroxidase (GPx)
      levels were measured in the cell extracts obtained from both cells incubated with
      different drugs. RESULTS: N-acetylcysteine increased the resistance of both cells
      against doxorubicin. DL-buthionine (S,R)-sulfoximine decreased NAC-enhanced MRP1
      mediated doxorubicin resistance, indicating that induction of MRP1-mediated
      doxorubicin resistance depends on GSH synthesis. Doxorubicin decreased the
      cellular GSH concentration and increased GPx activity. Glutathione S-transferase
      activity was decreased by NAC. CONCLUSION: Our results demonstrate that NAC
      enhances MRP1-mediated doxorubicin resistance and this effect depends on GSH
      synthesis. DL-buthionine (S,R)-sulfoximine seems a promising chemotherapy
      improving agent in MRP1 overexpressing tumour cells.

PMID- 15473894
TI  - Myelodysplasia-associated autoimmunity: clinical and pathophysiologic concepts.
AB  - Myelodysplastic syndrome (MDS), an acquired clonal disorder of haemopoietic
      progenitor cells, is characterized by haemopoietic insufficiency associated with
      cytopenias, leading to serious morbidity plus the additional risk of leukaemic
      transformation. In MDS an acquired insult to the haemopoietic stem cell leads to
      impaired differentiation and myelodysplasia. However, there is increasing
      evidence that the marrow failure of MDS is immune-mediated. A model of MDS
      pathophysiology suggests that transformation of normal stem cells induces an
      autoimmune T-cell response with the bone marrow as the target organ. This
      autoimmune attack results in chronic overproduction of pro-apoptotic cytokines,
      especially tumour necrosis factor alpha (TNFalpha). In addition, several reports
      have revealed that approximately 10% of MDS patients have clinical autoimmune
      disorders. This review illustrates the cellular/molecular mechanisms and the
      implication of the tumour suppressor gene interferon regulatory factor-1 (IRF-1)
      in the pathophysiology of MDS-associated autoimmune deregulation.

PMID- 15473895
TI  - Granulocyte function in patients with L-ferritin iron-responsive element (IRE)
      39C-->T-positive hereditary hyperferritinaemia-cataract syndrome.
AB  - BACKGROUND: Hereditary hyperferritinaemia-cataract syndrome (HHCS) is an
      autosomal dominant trait associated with mutations in the iron responsive element
      (IRE) of the ferritin light-chain (L-ferritin) gene. Patients typically show
      elevated serum ferritin concentrations without iron overload and a bilateral
      cataract. Hyperferritinaemia can be associated with granulocyte dysfunction in
      patients with thalassemia beta and in haemodialysis patients. The effect of
      increased L-ferritin levels on granulocyte function in patients with HHCS is
      unknown. MATERIAL AND METHODS: We examined glucose uptake, oxidative burst,
      chemotaxis, phagocytosis, apoptosis and intracellular calcium concentrations in
      polymorphonuclear leucocytes (PMNLs) of five affected members of a family with
      HHCS and in five healthy individuals matched for age and gender. RESULTS:
      Mutation testing revealed a 39C-->T transition in IRE in all five patients with
      HHCS. Serum ferritin levels of patients ranged between 907 and 2030 microg L(-1),
      respectively. In comparison with healthy individuals, PMNLs of patients with HHCS
      showed a significant increase in PMA-mediated stimulation of the oxidative burst,
      as well as a significantly higher stimulation of glucose uptake but no difference
      with respect to chemotaxis, phagocytosis, apoptosis and intracellular calcium
      concentrations. CONCLUSION: In summary, our study suggests that
      hyperferritinaemia in patients with IRE 39C-->T-positive HHCS is associated with
      activation of PMNLs but not with disturbance of fundamental PMNL function.

PMID- 15473896
TI  - Lipid-lowering and anti-inflammatory effects of tetradecylthioacetic acid in HIV
      infected patients on highly active antiretroviral therapy.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) often leads to a
      dramatic improvement in clinical, viral and immunologic parameters in HIV
      infected individuals. However, the emergence of long-term side-effects of HAART
      and in particular dylipidaemia is increasingly reported. Based on the potential
      lipid-lowering and immunomodulatory properties of tetradecylthioacetic acid (TTA)
      we examined whether TTA in combination with dietary intervention could modify
      lipid levels in peripheral blood in HIV-infected patients on HAART. MATERIALS AND
      METHODS: Ten HIV-infected patients on protease inhibitor-based HAART with
      hyperlipidaemia followed a cholesterol-lowering diet throughout the study period
      (8 weeks). During the last 4 weeks of the study all patients received TTA (1 g
      qd) in addition to the cholesterol-lowering diet. RESULTS: Our main and novel
      findings were: (i) TTA in combination with dietary intervention reduces total
      cholesterol, LDL cholesterol, triglycerides and LDL/HDL cholesterol in these
      patients, and a particularly suppressing effect was observed during the TTA phase
      regarding total cholesterol. (ii) During the TTA phase, the cholesterol-lowering
      effect was accompanied by a significant reduction in plasma levels of tumour
      necrosis factor alpha. (iii) Our studies in peripheral blood mononuclear cells
      from these patients and in the liver from wild-type mice receiving TTA suggest
      that the hypolipidaemic effects of TTA may involve up-regulation of scavenger and
      LDL-receptor expression. CONCLUSIONS: Although few patients were studied, the
      present pilot study suggests that TTA combined with dietary intervention could be
      an interesting therapeutic approach in HIV-infected patients on HAART,
      potentially resulting in both hypolipidaemic and anti-inflammatory effects.

PMID- 15473897
TI  - Screening of healthy school children aged 6-17 years old for immunoglobulin A
      deficiency in eastern Turkey.

PMID- 15473899
TI  - Health, human rights and mobilization of resources for health.
AB  - BACKGROUND: There has been an increased interest in the role of a human rights
      framework to mobilize resources for health. DISCUSSION: This paper argues that
      the human rights framework does provide us with an appropriate understanding of
      what values should guide a nation's health policy, and a potentially powerful
      means of moving the health agenda forward. It also, however, argues that appeals
      to human rights may not necessarily be effective at mobilizing resources for
      specific health problems one might want to do something about. Specifically, it
      is not possible to argue that a particular allocation of scarce health care
      resources should be changed to a different allocation, benefiting other groups.
      Lack of access to health care services by some people only shows that something
      has to be done, but not what should be done. SUMMARY: The somewhat weak claim
      identified above together with the obligation to realize progressively a right to
      health can be used to mobilize resources for health.

PMID- 15473900
TI  - Improved gene delivery to human saphenous vein cells and tissue using a peptide
      modified adenoviral vector.
AB  - The establishment of efficient gene delivery to target human tissue is a major
      obstacle for transition of gene therapy from the pre-clinical phases to the
      clinic. The poor long-term patency rates for coronary artery bypass grafting
      (CABG) is a major clinical problem that lacks an effective and proven
      pharmacological intervention. Late vein graft failure occurs due to neointima
      formation and accelerated atherosclerosis. Since CABG allows a clinical window of
      opportunity to genetically modify vein ex vivo prior to grafting it represents an
      ideal opportunity to develop gene-based therapies. Adenoviral vectors have been
      frequently used for gene delivery to vein ex vivo and pre-clinical studies have
      shown effective blockade in neointima development by overexpression of candidate
      therapeutic genes. However, high titers of adenovirus are required to achieve
      sufficient gene delivery to provide therapeutic benefit. Improvement in the
      uptake of adenovirus into the vessel wall would therefore be of benefit. Here we
      determined the ability of an adenovirus serotype 5 vector genetically-engineered
      with the RGD-4C integrin targeting peptide inserted into the HI loop (Ad-RGD) to
      improve the transduction of human saphenous vein smooth muscle cells (HSVSMC),
      endothelial cells (HSVEC) and intact saphenous vein compared to a non-modified
      virus (Ad-CTL). We exposed each cell type to virus for 10, 30 or 60 mins and
      measured transgene at 24 h post infection. For both HSVSMC and HSVEC Ad-RGD
      mediated increased transduction, with the largest increases observed in HSVSMC.
      When the experiments were repeated with intact human saphenous vein (the ultimate
      clinical target for gene therapy), again Ad-RGD mediated higher levels of
      transduction, at all clinically relevant exposures times (10, 30 and 60 mins
      tissue:virus exposure). Our study demonstrates the ability of peptide-modified Ad
      vectors to improve transduction to human vein graft cells and tissue and has
      important implications for gene therapy for CABG.

PMID- 15473901
TI  - Feasibility of rapid and automated importation of 3D echocardiographic left
      ventricular (LV) geometry into a finite element (FEM) analysis model.
AB  - BACKGROUND: Finite element method (FEM) analysis for intraoperative modeling of
      the left ventricle (LV) is presently not possible. Since 3D structural data of
      the LV is now obtainable using standard transesophageal echocardiography (TEE)
      devices intraoperatively, the present study describes a method to transfer this
      data into a commercially available FEM analysis system: ABAQUS. METHODS: In this
      prospective study TomTec LV Analysis TEE Software was used for semi-automatic
      endocardial border detection, reconstruction, and volume-rendering of the
      clinical 3D echocardiographic data. A newly developed software program MVCP
      FemCoGen, written in Delphi, reformats the TomTec file structures in five
      patients for use in ABAQUS and allows visualization of regional deformation of
      the LV. RESULTS: This study demonstrates that a fully automated importation of 3D
      TEE data into FEM modeling is feasible and can be efficiently accomplished in the
      operating room. CONCLUSION: For complete intraoperative 3D LV finite element
      analysis, three input elements are necessary: 1. time-gaited, reality-based
      structural information, 2. continuous LV pressure and 3. instantaneous tissue
      elastance. The first of these elements is now available using the methods
      presented herein.

PMID- 15473902
TI  - Erytrocyte membrane anionic charge in type 2 diabetic patients with retinopathy.
AB  - BACKGROUND: The Steno hypothesis states that changes in basement membrane anionic
      charge leads to diabetic microvascular complications. In diabetic nephropathy,
      loss of basement membrane glycosaminoglycans and the association between
      glomerular basement membrane heparan sulphate and proteinuria has been
      documented. A correlation between erythrocyte surface and the glomerular
      capillary wall charges has also been observed. The aim of this study is to
      evaluate the relationship between retinopathy and erythrocyte anionic charge and
      urinary glycosaminoglycan excretion in type 2 diabetic patients. METHODS: 49
      subjects (58 +/- 7 yrs, M/F 27/22) with type 2 diabetes with proliferative
      retinopathy (n = 13), nonproliferative retinopathy (n = 13) and without
      retinopathy (n = 23) were included in the study. 38 healthy subjects were
      selected as control group (57 +/- 5 yrs, M/F 19/19). Erythrocyte anionic charge
      (EAC) was determined by the binding of the cationic dye, alcian blue. Urinary
      glycosaminoglycan and microalbumin excretion were measured. RESULTS: EAC was
      significantly decreased in diabetic patients with retinopathy (255 +/- 30 ng
      alcian blue/10(6) RBC, 312 +/- 30 ng alcian blue/10(6) RBC for diabetic and
      control groups respectively, p < 0.001). We did not observe an association
      between urinary GAG and microalbumin excretion and diabetic retinopathy. EAC is
      found to be negatively correlated with microalbuminuria in all groups.
      CONCLUSIONS: We conclude that type 2 diabetic patients with low erythrocyte
      anionic charge are associated with diabetic retinopathy. Reduction of negative
      charge of basement membranes may indicate general changes in microvasculature
      rather than retinopathy. More prospective and large studies needs to clarify the
      role of glycosaminoglycans on progression of retinopathy in type 2 diabetic
      patients.

PMID- 15473903
TI  - Integrating linkage and radiation hybrid mapping data for bovine chromosome 15.
AB  - BACKGROUND: Bovine chromosome (BTA) 15 contains a quantitative trait loci (QTL)
      for meat tenderness, as well as several breaks in synteny with human chromosome
      (HSA) 11. Both linkage and radiation hybrid (RH) maps of BTA 15 are available,
      but the linkage map lacks gene-specific markers needed to identify genes
      underlying the QTL, and the gene-rich RH map lacks associations with marker
      genotypes needed to define the QTL. Integrating the maps will provide information
      to further explore the QTL as well as refine the comparative map between BTA 15
      and HSA 11. A recently developed approach to integrating linkage and RH maps uses
      both linkage and RH data to resolve a consensus marker order, rather than
      aligning independently constructed maps. Automated map construction procedures
      employing this maximum-likelihood approach were developed to integrate BTA RH and
      linkage data, and establish comparative positions of BTA 15 markers with HSA 11
      homologs. RESULTS: The integrated BTA 15 map represents 145 markers; 42 shared by
      both data sets, 36 unique to the linkage data and 67 unique to RH data. Sequence
      alignment yielded comparative positions for 77 bovine markers with homologs on
      HSA 11. The map covers approximately 32% of HSA 11 sequence in five segments of
      conserved synteny, another 15% of HSA 11 is shared with BTA 29. Bovine and human
      order are consistent in portions of the syntenic segments, but some rearrangement
      is apparent. Comparative positions of gene markers near the meat tenderness QTL
      indicate the region includes separate segments of HSA 11. The two microsatellite
      markers flanking the QTL peak are between defined syntenic segments. CONCLUSIONS:
      Combining data to construct an integrated map not only consolidates information
      from different sources onto a single map, but information contributed from each
      data set increases the accuracy of the map. Comparison of bovine maps with well
      annotated human sequence can provide useful information about genes near mapped
      bovine markers, but bovine gene order may be different than human. Procedures to
      connect genetic and physical mapping data, build integrated maps for livestock
      species, and connect those maps to more fully annotated sequence can be
      automated, facilitating the maintenance of up-to-date maps, and providing a
      valuable tool to further explore genetic variation in livestock.

PMID- 15473904
TI  - Genome-wide microarray analysis of TGFbeta signaling in the Drosophila brain.
AB  - BACKGROUND: Members of TGFbeta superfamily are found to play important roles in
      many cellular processes, such as proliferation, differentiation, development,
      apoptosis, and cancer. In Drosophila, there are seven ligands that function
      through combinations of three type I receptors and two type II receptors. These
      signals can be roughly grouped into two major TGFbeta pathways, the dpp/BMP and
      activin pathways, which signal primarily through thick veins (tkv) and baboon
      (babo). Few downstream targets are known for either pathway, especially targets
      expressed in the Drosophila brain. RESULTS: tkv and babo both affect the growth
      of tissues, but have varying effects on patterning. We have identified targets
      for the tkv and babo pathways by employing microarray techniques using activated
      forms of the receptors expressed in the brain. In these experiments, we compare
      the similarities of target genes of these two pathways in the brain. About 500 of
      13,500 examined genes changed expression at 95% confidence level (P < 0.05).
      Twenty-seven genes are co-regulated 1.5 fold by both the tkv and babo pathways.
      These regulated genes cluster into various functional groups such as DNA/RNA
      binding, signal transducers, enzymes, transcription regulators, and neuronal
      regulators. RNAi knockdown experiments of homologs of several of these genes show
      abnormal growth regulation, suggesting these genes may execute the growth
      properties of TGFbeta. CONCLUSIONS: Our genomic-wide microarray analysis has
      revealed common targets for the tkv and babo pathways and provided new insights
      into downstream effectors of two distinct TGFbeta like pathways. Many of these
      genes are novel and several genes are implicated in growth control. Among the
      genes regulated by both pathways is ultraspiracle, which further connects TGFbeta
      with neuronal remodeling.

PMID- 15473905
TI  - Content-rich biological network constructed by mining PubMed abstracts.
AB  - BACKGROUND: The integration of the rapidly expanding corpus of information about
      the genome, transcriptome, and proteome, engendered by powerful technological
      advances, such as microarrays, and the availability of genomic sequence from
      multiple species, challenges the grasp and comprehension of the scientific
      community. Despite the existence of text-mining methods that identify biological
      relationships based on the textual co-occurrence of gene/protein terms or
      similarities in abstract texts, knowledge of the underlying molecular connections
      on a large scale, which is prerequisite to understanding novel biological
      processes, lags far behind the accumulation of data. While computationally
      efficient, the co-occurrence-based approaches fail to characterize (e.g.,
      inhibition or stimulation, directionality) biological interactions. Programs with
      natural language processing (NLP) capability have been created to address these
      limitations, however, they are in general not readily accessible to the public.
      RESULTS: We present a NLP-based text-mining approach, Chilibot, which constructs
      content-rich relationship networks among biological concepts, genes, proteins, or
      drugs. Amongst its features, suggestions for new hypotheses can be generated.
      Lastly, we provide evidence that the connectivity of molecular networks extracted
      from the biological literature follows the power-law distribution, indicating
      scale-free topologies consistent with the results of previous experimental
      analyses. CONCLUSIONS: Chilibot distills scientific relationships from knowledge
      available throughout a wide range of biological domains and presents these in a
      content-rich graphical format, thus integrating general biomedical knowledge with
      the specialized knowledge and interests of the user. Chilibot
      http://www.chilibot.net can be accessed free of charge to academic users.

PMID- 15473906
TI  - Cdc42 Effector Protein 2 (XCEP2) is required for normal gastrulation and
      contributes to cellular adhesion in Xenopus laevis.
AB  - BACKGROUND: Rho GTPases and their downstream effector proteins regulate a diverse
      array of cellular processes during embryonic development, including
      reorganization of cytoskeletal architecture, cell adhesion, and transcription.
      Changes in the activation state of Rho GTPases are converted into changes in
      cellular behavior by a diversity of effector proteins, which are activated in
      response to changes in the GTP binding state of Rho GTPases. In this study we
      characterize the expression and function of one such effector, XCEP2, that is
      present during gastrulation stages in Xenopus laevis. RESULTS: In a search for
      genes whose expression is regulated during early stages of embryonic development
      in Xenopus laevis, a gene encoding a Rho GTPase effector protein (Xenopus Cdc42
      effector protein 2, or XCEP2) was isolated, and found to be highly homologous,
      but not identical, to a Xenopus sequence previously submitted to the Genbank
      database. These two gene sequences are likely pseudoalleles. XCEP2 mRNA is
      expressed at constant levels until mid- to late- gastrula stages, and then
      strongly down-regulated at late gastrula/early neurula stages. Injection of
      antisense morpholino oligonucleotides directed at one or both pseudoalleles
      resulted in a significant delay in blastopore closure and interfered with normal
      embryonic elongation, suggesting a role for XCEP2 in regulating gastrulation
      movements. The morpholino antisense effect could be rescued by co-injection with
      a morpholino-insensitive version of the XCEP2 mRNA. Antisense morpholino
      oligonucleotides were found to have no effect on mesodermal induction, suggesting
      that the observed effects were due to changes in the behavior of involuting
      cells, rather than alterations in their identity. XCEP2 antisense morpholino
      oligonucleotides were also observed to cause complete disaggregation of cells
      composing animal cap explants, suggesting a specific role of XCEP2 in maintenance
      or regulation of cell-cell adhesion in early embryos. This loss of cell adhesion
      could be rescued by co-injection with a morpholino-insensitive version of the
      XCEP2 mRNA. CONCLUSIONS: XCEP2 appears to be an essential component in the early
      developmental program in Xenopus laevis. XCEP2 is involved in maintenance of cell
      cell adhesion, and as such may constitute a regulatory component that could help
      to balance the need for tissue integrity and plasticity during the dynamic
      cellular rearrangements of gastrulation.

PMID- 15473907
TI  - Leptin receptor in the chicken ovary: potential involvement in ovarian
      dysfunction of ad libitum-fed broiler breeder hens.
AB  - In hens, the ovarian follicles committed to ovulation are arranged in an ordered
      follicular hierarchy. In standard broiler breeders hens genetically selected for
      high growth rate the reproductive function is clearly dysfunctional. Feed
      restriction is needed during reproductive development to limit the formation of
      excessive numbers of ovarian yellow follicles arranged in multiple hierarchies.
      To determine whether leptin is involved in the nutritional and reproductive
      interactions controlling follicular hierarchy in hens, blood leptin levels and
      ovarian expression of the leptin receptor mRNA were determined during follicle
      maturation in three chicken lines; a slow growing broiler "Label" genotype
      without reproductive dysfunction, a fast growing "Standard" genotype fed ad
      libitum or restricted and a fast growing "Experimental" line with intermediate
      reproductive performance levels. Whereas expression of the leptin receptor mRNA
      did not change in the theca, it clearly decreased with follicular differentiation
      in the granulosa of slow growing hens. In fast growing standard hens fed ad
      libitum and presenting significant reproductive dysfunction, the decrease was
      disrupted and dramatic up-regulation of granulosa cell expression of the leptin
      receptor was observed. On the other hand, feed restriction decreased the overall
      level of expression of the leptin receptor mRNA and restored the decrease with
      follicular growth. The level of expression of the leptin receptor probably
      modulates the action of leptin on follicular differentiation. Since blood leptin
      and other metabolic factors were not affected by the genotype or by nutritional
      state, the factors involved in the regulation of leptin receptor gene expression
      remain to be determined. This study demonstrates the involvement of leptin in the
      nutritional control of reproduction in birds. Leptin action on the ovary probably
      controls follicular hierarchy through the regulation of steroidogenesis.

PMID- 15473908
TI  - i-Genome: a database to summarize oligonucleotide data in genomes.
AB  - BACKGROUND: Information on the occurrence of sequence features in genomes is
      crucial to comparative genomics, evolutionary analysis, the analyses of
      regulatory sequences and the quantitative evaluation of sequences. Computing the
      frequencies and the occurrences of a pattern in complete genomes is time
      consuming. RESULTS: The proposed database provides information about sequence
      features generated by exhaustively computing the sequences of the complete
      genome. The repetitive elements in the eukaryotic genomes, such as LINEs, SINEs,
      Alu and LTR, are obtained from Repbase. The database supports various complete
      genomes including human, yeast, worm, and 128 microbial genomes. CONCLUSIONS:
      This investigation presents and implements an efficiently computational approach
      to accumulate the occurrences of the oligonucleotides or patterns in complete
      genomes. A database is established to maintain the information of the sequence
      features, including the distributions of oligonucleotide, the gene distribution,
      the distribution of repetitive elements in genomes and the occurrences of the
      oligonucleotides. The database can provide more effective and efficient way to
      access the repetitive features in genomes.

PMID- 15473910
TI  - Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment
      with imatinib mesylate: case report.
AB  - BACKGROUND: The management of unresectable or metastatic gastrointestinal stromal
      tumors (GISTs) has previously been difficult as they are resistant to
      conventional chemotherapy and radiation. The development of imatinib mesylate has
      made a major impact on the management of advanced GISTs. It is apparent that
      there are sanctuary sites such as the central nervous system where imatinib does
      not achieve adequate concentrations. We describe the case of a man with
      metastatic GIST who experienced multiple cerebral relapses of disease while
      systemic disease progression appeared to be controlled by imatinib. CASE
      PRESENTATION: A 47-year-old man presented in July 1999 with a jejunal GIST with
      multiple hepatic metastases. The jejunal primary was resected and after
      unsuccessful cytoreductive chemotherapy, the liver metastases were also resected
      in December 1999. The patient subsequently relapsed in August 2001 with
      symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular
      metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST.
      MRI and lumbar puncture excluded central nervous system involvement. The patient
      was commenced on imatinib 400 mg bd in September 2001 through a clinical trial.
      The symptoms improved with objective PET and CT scan response until December 2002
      when the patient developed a right-sided foot drop. MRI scan showed a left
      parasagittal tumor which was resected and confirmed histologically to be
      metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol
      but recommenced in February 2003 on a compassionate use program. The left
      parasagittal metastasis recurred and required subsequent re-excision in September
      2003 and January 2004. Control of the systemic GIST was temporarily lost on
      reduction of the dose of imatinib (due to limited drug supply) but on increasing
      the dose back to 800 mg per day, systemic disease was stabilized for a period of
      time before generalised progression occurred. CONCLUSION: This case illustrates
      that the brain can be a sanctuary site to treatment of GISTs with imatinib.
      Maintaining dosing of imatinib in the face of isolated sites of disease
      progression is also important, as other metastatic sites may still be sensitive.

PMID- 15473909
TI  - Transcriptional oscillation of canonical clock genes in mouse peripheral tissues.
AB  - BACKGROUND: The circadian rhythm of about 24 hours is a fundamental physiological
      function observed in almost all organisms from prokaryotes to humans.
      Identification of clock genes has allowed us to study the molecular bases for
      circadian behaviors and temporal physiological processes such as hormonal
      secretion, and has prompted the idea that molecular clocks reside not only in a
      central pacemaker, the suprachiasmatic nuclei (SCN) of hypothalamus in mammals,
      but also in peripheral tissues, even in immortalized cells. Furthermore, previous
      molecular dissection revealed that the mechanism of circadian oscillation at a
      molecular level is based on transcriptional regulation of clock and clock
      controlled genes. RESULTS: We systematically analyzed the mRNA expression of
      clock and clock-controlled genes in mouse peripheral tissues. Eight genes
      (mBmal1, mNpas2, mRev-erbalpha, mDbp, mRev-erbbeta, mPer3, mPer1 and mPer2; given
      in the temporal order of the rhythm peak) showed robust circadian expressions of
      mRNAs in all tissues except testis, suggesting that these genes are core
      molecules of the molecular biological clock. The bioinformatics analysis revealed
      that these genes have one or a combination of 3 transcriptional elements (RORE,
      DBPE, and E-box), which are conserved among human, mouse, and rat genome
      sequences, and indicated that these 3 elements may be responsible for the
      biological timing of expression of canonical clock genes. CONCLUSIONS: The
      observation of oscillatory profiles of canonical clock genes is not only useful
      for physiological and pathological examination of the circadian clock in various
      organs but also important for systematic understanding of transcriptional
      regulation on a genome-wide basis. Our finding of the oscillatory expression of
      canonical clock genes with a temporal order provides us an interesting
      hypothesis, that cyclic timing of all clock and clock-controlled genes may be
      dependent on several transcriptional elements including 3 known elements, E-box,
      RORE, and DBPE.

PMID- 15473911
TI  - Variation suggestive of horizontal gene transfer at a lipopolysaccharide (lps)
      biosynthetic locus in Xanthomonas oryzae pv. oryzae, the bacterial leaf blight
      pathogen of rice.
AB  - BACKGROUND: In animal pathogenic bacteria, horizontal gene transfer events (HGT)
      have been frequently observed in genomic regions that encode functions involved
      in biosynthesis of the outer membrane located lipopolysaccharide (LPS). As a
      result, different strains of the same pathogen can have substantially different
      lps biosynthetic gene clusters. Since LPS is highly antigenic, the variation at
      lps loci is attributed to be of advantage in evading the host immune system.
      Although LPS has been suggested as a potentiator of plant defense responses,
      interstrain variation at lps biosynthetic gene clusters has not been reported for
      any plant pathogenic bacterium. RESULTS: We report here the complete sequence of
      a 12.2 kb virulence locus of Xanthomonas oryzae pv. oryzae (Xoo) encoding six
      genes whose products are homologous to functions involved in LPS biosynthesis and
      transport. All six open reading frames (ORFs) have atypical G+C content and
      altered codon usage, which are the hallmarks of genomic islands that are acquired
      by horizontal gene transfer. The lps locus is flanked by highly conserved genes,
      metB and etfA, respectively encoding cystathionine gamma lyase and electron
      transport flavoprotein. Interestingly, two different sets of lps genes are
      present at this locus in the plant pathogens, Xanthomonas campestris pv.
      campestris (Xcc) and Xanthomonas axonopodis pv. citri (Xac). The genomic island
      is present in a number of Xoo strains from India and other Asian countries but is
      not present in two strains, one from India (BXO8) and another from Nepal
      (Nepal624) as well as the closely related rice pathogen, Xanthomonas oryzae pv.
      oryzicola (Xoor). TAIL-PCR analysis indicates that sequences related to Xac are
      present at the lps locus in both BXO8 and Nepal624. The Xoor strain has a hybrid
      lps gene cluster, with sequences at the metB and etfA ends, being most closely
      related to sequences from Xac and the tomato pathogen, Pseudomonas syringae pv.
      tomato respectively. CONCLUSION: This is the first report of hypervariation at an
      lps locus between different strains of a plant pathogenic bacterium. Our results
      indicate that multiple HGT events have occurred at this locus in the xanthomonad
      group of plant pathogens.

PMID- 15473912
TI  - Significance of MDR1 and multiple drug resistance in refractory human epileptic
      brain.
AB  - BACKGROUND: The multiple drug resistance protein (MDR1/P-glycoprotein) is
      overexpressed in glia and blood-brain barrier (BBB) endothelium in drug
      refractory human epileptic tissue. Since various antiepileptic drugs (AEDs) can
      act as substrates for MDR1, the enhanced expression/function of this protein may
      increase their active extrusion from the brain, resulting in decreased
      responsiveness to AEDs. METHODS: Human drug resistant epileptic brain tissues
      were collected after surgical resection. Astrocyte cell cultures were established
      from these tissues, and commercially available normal human astrocytes were used
      as controls. Uptake of fluorescent doxorubicin and radioactive-labeled Phenytoin
      was measured in the two cell populations, and the effect of MDR1 blockers was
      evaluated. Frozen human epileptic brain tissue slices were double immunostained
      to locate MDR1 in neurons and glia. Other slices were exposed to toxic
      concentrations of Phenytoin to study cell viability in the presence or absence of
      a specific MDR1 blocker. RESULTS: MDR1 was overexpressed in blood vessels,
      astrocytes and neurons in human epileptic drug-resistant brain. In addition, MDR1
      mediated cellular drug extrusion was increased in human 'epileptic' astrocytes
      compared to 'normal' ones. Concomitantly, cell viability in the presence of
      cytotoxic compounds was increased. CONCLUSIONS: Overexpression of MDR1 in
      different cell types in drug-resistant epileptic human brain leads to functional
      alterations, not all of which are linked to drug pharmacokinetics. In particular,
      the modulation of glioneuronal MDR1 function in epileptic brain in the presence
      of toxic concentrations of xenobiotics may constitute a novel cytoprotective
      mechanism.

PMID- 15473913
TI  - A report of dangerously high carbon monoxide levels within the passenger
      compartment of a snow-obstructed vehicle.
AB  - BACKGROUND: We sought to determine how quickly carbon monoxide would accumulate
      in the passenger compartment of a snow-obstructed vehicle. METHODS: A 1992 sedan
      was buried in snow to the level of the undercarriage, the ignition was then
      engaged and carbon monoxide levels recorded at 2.5-minute intervals. The primary
      outcome was the time at which a lethal carbon monoxide level was detected. Six
      trials were conducted: windows closed; windows open one inch; windows open 6
      inches; windows closed and tailpipe swept clear of snow; windows closed and one
      cubic foot of snow removed around tailpipe; windows closed and tailpipe
      completely cleared of snow to ground level in a path 12 inches wide. RESULTS:
      Lethal levels of carbon monoxide occurred within 2.5 minutes in the vehicle when
      the windows were closed, within 5 minutes when the widows were opened one inch,
      and within 7.5 minutes when the widows were opened six inches. Dangerously high
      levels of carbon monoxide were detected within the vehicle when the tailpipe had
      been swept clear of snow and when a one cubic foot area had been cleared around
      the tailpipe. When the tailpipe was completely unobstructed the carbon monoxide
      level was zero. CONCLUSIONS: Lethal levels of carbon monoxide occurred within
      minutes in this snow-obstructed vehicle.

PMID- 15473915
TI  - Polymorphisms in wolframin (WFS1) gene are possibly related to increased risk for
      mood disorders.
AB  - Wolfram syndrome gene (WFS1) has been suggested to have a role in the
      susceptibility for mood disorders. A 26-fold increased risk for psychiatric
      disorders in WFS1 mutation carriers has been suggested. In this study we tested
      the hypothesis that the WFS1 gene is related to the risk for mood disorders. We
      analysed 28 single-nucleotide polymorphisms (SNPs) of the WFS1 gene in 224
      unrelated patients with major depressive disorder and bipolar disorder and in 160
      healthy control subjects. Patients were further stratified according to their
      comorbidity with anxiety disorders. We applied arrayed primer extension (APEX)
      based genotyping technology followed by association and haplotype analysis. Five
      SNPs in the WFS1 gene were associated with major depressive disorder, and three
      SNPs with bipolar disorder. Haplotype analysis revealed a common GTA haplotype,
      formed by SNPs 684C/G, 1185C/T and 1832G/A, conferring risk for affective
      disorders. Specifically, for major depression the GTA haplotype has an OR of 1.59
      (p = 0.01) and for bipolar disorder an OR of 1.89 (p = 0.03). These results
      support the hypothesis that the WFS1 gene is involved in the genetic
      predisposition for mood disorders.

PMID- 15473914
TI  - Low dose pramipexole is neuroprotective in the MPTP mouse model of Parkinson's
      disease, and downregulates the dopamine transporter via the D3 receptor.
AB  - BACKGROUND: Our aim was to determine if pramipexole, a D3 preferring agonist,
      effectively reduced dopamine neuron and fiber loss in the 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) mouse model when given at intraperitoneal doses
      corresponding to clinical doses. We also determined whether subchronic treatment
      with pramipexole regulates dopamine transporter function, thereby reducing
      intracellular transport of the active metabolite of MPTP, 1-methyl-4
      phenylpyridinium (MPP+). METHODS: Ten 12-month old C57BL/6 mice were treated with
      MPTP (or saline) twice per day at 20 mg/kg s.c. (4 injections over 48 h). Mice
      were pretreated for 3 days and during the 2-day MPTP regimen with pramipexole
      (0.1 mg/kg/day) or saline. Stereological quantification of dopamine neuron number
      and optical density measurement of dopamine fiber loss were carried out at 1 week
      after treatment, using immunostaining for dopamine transporter (DAT) and tyrosine
      hydroxylase (TH). Additional wild-type (WT) and D3 receptor knockout (KO) mice
      were treated for 5 days with pramipexole (0.1 mg/kg/day) or vehicle. The kinetics
      of [3H]MPP+ and [3H]DA uptake (Vmax and Km) were determined 24 h later; and at 24
      h and 14 days dopamine transporter density was measured by quantitative
      autoradiography. RESULTS: Pramipexole treatment completely antagonized the
      neurotoxic effects of MPTP, as measured by substantia nigra and ventral tegmental
      area TH-immunoreactive cell counts. MPTP- induced loss of striatal innervation,
      as measured by DAT-immunoreactivity, was partially prevented by pramipexole, but
      not with regard to TH-IR. Pramipexole also reduced DAT- immunoreactivity in non
      MPTP treated mice. Subchronic treatment with pramipexole lowered the Vmax for
      [3H]DA and [3H]MPP+ uptake into striatal synaptosomes of WT mice. Pramipexole
      treatment lowered Vmax in WT but not D3 KO mice; however, D3 KO mice had lower
      Vmax for [3H]DA uptake. There was no change in DAT number in WT with pramipexole
      treatment or D3 KO mice at 24 h post-treatment, but there was a reduction in WT
      pramipexole treated and not in D3 KO mice at 14 days post-treatment. CONCLUSION:
      These results suggest that protection occurs at clinically suitable doses of
      pramipexole. Protection could be due to a reduced amount of MPP+ taken up into DA
      terminals via DAT. D3 receptor plays an important role in this regulation of
      transporter uptake and availability.

PMID- 15473917
TI  - [Preparation and feasibility of superparamagnetic dextran iron oxide
      nanoparticles as gene carrier].
AB  - BACKGROUND & OBJECTIVE: Application of magnetic nano- particles as gene carrier
      in gene therapy of tumor has developed quickly. To obtain a new type non-viral
      gene introduction and therapy system,which is convenient,and can drive target
      gene to express highly and stably,this study was designed to explore the
      preparation of superparamagnetic dextran iron oxide nanoparticles(SDION),and the
      feasibility of SDION used as gene carrier in vitro. METHODS: SDION were prepared
      by chemical co-precipitation,separated by gel filtration chromatography on
      Sephacryl S-300HR,and centrifugation techniques,characterized by transmission
      electron microscopy,laser scattering system,and vibrating sample magnetometer
      signal processor. The green fluorescent protein-C2 (GFP-C2) plasmid was used as
      target gene. SDION-GFP- C2 compounds were synthesized by oxidation-reduction
      reaction. The connection rate of SDION and GFP-C2 was analyzed by agarose
      electrophoresis,and evaluated by measuring concentration of GFP in the
      supernatant after centrifugation. Liposome transfection was used as control,the
      efficiencies of SDION and liposome in transferring GFP gene into human bladder
      cancer BIU-87 cells were evaluated under fluorescence microscope in vitro.
      RESULTS: The diameter of SDION ranged from 3 nm to 8 nm, the effective diameter
      was 59.2 nm, and the saturation magnetization was 0.23 emu/g. After oxidized by
      sodium periodate of 10 mmol/L,and deoxidized by sodium hydride boron of 0.5
      mol/L, SDION could connect with GFP in maximum degree,the transfection efficiency
      of SDION as gene carrier was about 45%, even higher than that of liposome (about
      30%). CONCLUSION: SDION could connect with GFP plasmid by oxidation- reduction
      reaction,and success to transfer GFP gene into human bladder cancer BIU-87 cells
      in vitro.

PMID- 15473918
TI  - [Molecular cloning and functional analysis of STGC3 - a novel gene on chromosome
      3p21].
AB  - BACKGROUND & OBJECTIVE: A locus of loss of heterozygosity (LOH) with high
      frequency has been found on chromosome 3p21 in nasopharyngeal carcinoma (NPC). On
      the basis of our former research, this study was designed to clone and analyze a
      novel NPC-associated gene at this locus. METHODS: The full-length cDNA sequence
      of this gene was obtained by plasmid cDNA sequencing and RACE,and analyzed by
      bioinformatics. The pEGFP-C2/STGC3 fusion mammalian expression vector was
      constructed, and transfected into COS7 and CNE2 cell lines mediated by lipofectin
      to analyze the subcellular localization of gene expressing proteins. The
      expression of STGC3 was detected in normal tissues and tumor cell lines by
      Northern blot. RESULTS: An 1 271 bp full-length cDNA sequence of gene,which had
      no obvious homology with other known genes in bioinformatic databases,was
      obtained. This gene,named STGC3 (GenBank accession number:AY078383), localized on
      chromosome 3p21, and encodes a protein consisting of 146 amino acids. Protein
      localization analysis under fluorescent microscope indicated that STGC3 fusion
      protein was distributed in nucleus and cytoplasm 24-48 hours after transfection.
      MTE(TM)Array2 Northern blot analysis showed STGC3 expressed in both normal
      tissues and tumor cells,while its expression down-regulated in many tumor cell
      lines, such as Burkitt's lymphoma cell line Daudi. CONCLUSIONS: STGC3 is a novel
      gene, and down-regulated in NPC and many other tumor cell lines. STGC3 fusion
      protein distributes in cytoplasm and nucleus.

PMID- 15473919
TI  - [Establishment of protein profile of human small cell lung cancer cell line NCI
      H446].
AB  - BACKGROUND & OBJECTIVE: Small cell lung cancer (SCLC) is particularly aggressive,
      and characterized by rapid growth and early metastasis. At present, there is no
      data concerning SCLC two-dimensional polyacrylamide gel electrophoresis (2-DE)
      reference map,and its protein profiles in public databases. This study was to
      establish a well-resolved, reproducible 2-DE map of proteome in SCLC cell line
      NCI-H446, and analyze its protein profiles. METHODS: Two-DE was applied to
      separate the total proteins of NCI-H446 cells, which were then silver-stained in
      the gel. Well-separated protein spots were selected from the gel by ImageMaster
      2D analysis system. Matrix-assisted laser desorption/ionization time of flight
      mass spectrometry (MALDI-TOF-MS), peptide map fingerprinting (PMF),and database
      searching were used to identify the protein spots. RESULTS: Clear,well-resolved,
      reproducible 2-DE patterns of proteome in NCI-H446 cells were obtained. The
      average protein spots of 3 gels were 1506+/-74; and 1412+/-56 spots were matched
      with an average matching rate of 93.4%. The average deviation of spot position
      was (0.96+/-0.27) mm in IEF direction, and (1.24+/-0.41) mm in SDS-PAGE direction
      indicating relatively good reproducibility of the protein spots. Fifty-eight
      proteins were identified, certain proteins were products of oncogenes, and others
      were involved in cell cycle regulation, and signal transduction. CONCLUSIONS: A
      reference map of NCI-H446 cells was established,certain proteins were identified
      by MALDI-TOF-MS and PMF. These data will be useful for establishing human SCLC
      proteome database.

PMID- 15473920
TI  - [Isolation of differentially expressed cDNA sequences in human gastric carcinoma
      by cDNA microarray].
AB  - BACKGROUND & OBJECTIVE: Some gastric carcinoma-related genes haven't been
      identified yet. The study was designed to isolate and identify differentially
      expressed cDNA sequences in gastric carcinoma, and further clone gastric
      carcinoma-related genes. METHODS: The differences of gene expression profile
      between 30 gastric carcinoma tissues and their adjacent normal tissues were
      analyzed by cDNA microarray which representing about 4 892 cDNA sequences, the
      differentially expressed cDNA sequences were analyzed by bioinformatics, and
      selected cDNA sequences were confirmed by reverse transcripase-polymerase chain
      reaction (RT-PCR). RESULTS: A total of 33 differentially expressed cDNA sequences
      were identified in gastric carcinoma, among which 18 up-regulated in gastric
      carcinoma,while 15 down-regulated. MDSCBC11 clone,represented a novel gene,
      located in chromosome band 1p35-36, and significantly down-regulated in 13 of 30
      (43%) gastric carcinomas. CONCLUSIONS: Some gastric carcinoma-related cDNA
      sequences have been identified,they might be involved in pathogenesis of gastric
      carcinoma. This study provides a useful clue for further clone gastric carcinoma
      related genes.

PMID- 15473921
TI  - [Expression establishment and functional analysis of breast cancer resistance
      protein with doxycycline induced tet regulating system in mouse fibroblast cell
      line PA317].
AB  - BACKGROUND & OBJECTIVE: Breast cancer resistance protein (BCRP), discovered in
      1998, is a novel member of ATP-binding cassette (ABC) membrane transporters
      superfamily. This study was to establish the functional expression of BCRP with
      doxycycline (Dox) induced Tet regulating system in mouse fibroblast cell line
      PA317, provide an ideal experimental platform for understanding the mechanism of
      BCRP-mediated drug resistance, and develop effective methods to reverse the drug
      resistance. METHODS: Tet-on regulating plasmid was transferred into PA317 cells
      under the Dox induced Tet-on regulating system, and stable expression of Tet-on
      was established in PA317 cells through G418 selection. The response plasmid of
      recombinant pTRE-BCRP was transferred into positive PA317/Tet-on cells, and
      stable expression of BCRP was established through hygromycin selection. Six
      single cellular clones were taken and cultivated in amplification. Positive
      PA317/Tet-on/TRE-BCRP cells, which showed well dose-response in expression of
      BCRP with different concentration of Dox induction, were selected by both reverse
      transcriptase-polymerase chain reaction (RT-PCR) and Western blot. The inhibitory
      effects of mitoxantrone on positive PA317/Tet-on/TRE-BCRP cells with various
      concentrations of Dox induction were detected by MTT method. Ko143, a specific
      inhibitor of BCRP, was used to detect the drug sensitivity of positive PA317/Tet
      on/TRE-BCRP cells to mitoxantrone. Fluorescence intensity of remaining
      intracellular mitoxantrone in positive PA317/Tet-on/TRE-BCRP cells with different
      expression of BCRP was analyzed by flow cytometry (FCM). RESULTS: The positive
      No.5 PA317/Tet-on /TRE-BCRP cell clone showed well dose-response in expression of
      BCRP with different concentration of Dox induction; its drug-resistance against
      mitoxantrone has positive correlation with BCRP expression (r=0.995, P=0.002);
      its drug sensitivity to mitoxantrone was significantly enhanced by Ko143 (P<
      0.05). Furthermore, different expression of BCRP induced by various
      concentrations of Dox caused different intracellular mitoxantrone retention in
      this cell clone. CONCLUSION: Functional expression of BCRP under Dox induced Tet
      regulating system was successfully established in PA317 cells, which provided an
      ideal experimental platform for further study of BCRP.

PMID- 15473922
TI  - [Effect of transferred NK4 gene on biological characteristics of human pancreatic
      cancer cell line SW1990].
AB  - BACKGROUND & OBJECTIVE: Hepatocyte growth factor (HGF) plays an important role in
      the regulation of migration, invasion,and angiogenesis of cancer via the
      activation of its receptor, c-Met. NK4 is not only an antagonist of HGF but also
      an angiogenesis inhibitor. The blockade of HGF/c-Met signal pathway and tumor
      angiogenesis may be a new strategy for cancer treatment. This study was designed
      to construct eukaryotic expressing vector of NK4 gene, transfer it into human
      pancreatic cancer cell line SW1990, and observe the effect of transfected NK4
      gene on the biological behaviors of SW1990 cells,and its expression in SW1990
      cells. METHODS: The recombinant of pcDNA3/hNK4 plasmid was digested by
      restrictive enzyme,NK4 gene was cloned into a high effective eukaryotic
      expressing vector pRC/CMV2, and the recombinant of pRC/CMV2-hNK4 plasmid was
      transiently introduced into SW1990 cells by lipofectamine. Reverse transcriptase
      polymerase chain reaction (RT-PCR),and Western blot were used to detect the
      expression of NK4 at mRNA, and protein levels,respectively. Migration, and
      invasion capabilities of the transfected cells were evaluated by Transwall
      chamber, and Matrigel invasion chamber, respectively. RESULTS: Expressions of NK4
      gene after lipofectamine mediated transfection were observed in SW1990 cells,
      expected fragment of 453 bp has been amplified by RT-PCR, and Western blot
      analysis showed positive expression of NK4 protein (50 KDa). NK4 gene had no
      inhibitory effect on the growth of SW1990 cells (2.2x10(5) vs 2.5x10(5), P
      >0.05), while it had significantly suppressive effect on the migration and
      invasion of SW1990 cells driven by HGF or fibroblasts (P< 0.01). CONCLUSION: NK4
      gene transfection may inhibit spreading and invasion of pancreatic cancer cells,
      which would play an important role in the anti-metastasis therapy for pancreatic
      cancer.

PMID- 15473923
TI  - [Apoptosis of hepatocarcinoma cell line HLE induced by the combination of wild
      type P53 gene and 1,2:5,6-dianhydro-3,4-diacetylgalactitol].
AB  - BACKGROUND & OBJECTIVE: P53 gene is a tumor suppressor gene,and its mutation in
      human tumor cells is frequently observed. Previous studies revealed that wild
      type p53 (wt-p53)gene can suppress proliferation ,and induce apoptosis of tumor
      cells. However,the enhancive effect of wt-p53 on apoptosis of tumor cells is not
      so obvious when it is used alone. Therefore,it is a new field for tumor research
      that wt-p53 gene combined with drug is used to enhance apoptosis rate of tumor
      cells. This study was to investigate the enhancement effect of the combination of
      wt-p53 and 1,2:5,6-dianhydro-3,4-diacetylgalactitol (DADAG)on apoptosis of human
      hepatocarcinoma cell line HLE. METHODS: HLE cells were transfected with pUHD10-3
      p53 plasmid contained wt-p53 gene,and treated with DADAG. After 96-hour
      treatment,apoptosis was evaluated by flow cytometry and DNA electrophoresis.
      RESULTS: The apoptosis rates were: 1.4% in untreated group, 3.5% in pUHD10-3
      transfection group, 32.6% in DADAG group, 43.4% in pUHD10-3-p53-transfection
      group, and 74.6% in pUHD10-3-p53-transfection plus DADAG-treatment group. DNA
      ladder was observed in pUHD10-3-p53-transfection plus DADAG-treatment group.
      CONCLUSION: Apoptosis of HLE cells could be induced by both wt-p53 gene and
      DADAG,and the effect was more obvious when HLE cells were treated by the
      combination of wt-p53 gene and DADAG.

PMID- 15473925
TI  - [Molecular mechanism of LRIG1 cDNA-induced apoptosis in human glioma cell line
      H4].
AB  - BACKGROUND & OBJECTIVE: Leucine-rich repeats and immunoglobulin-like domains
      1(LRIG1)is a kind of transmembrane glycoprotein,which is induced by epidermal
      growth factor (EGF),and develops inhibitory negative feedback by specific binding
      with epidermal growth factor receptor (EGFR). This research was to explore the
      molecular mechanism of LRIG1 inhibiting EGFR signal pathway. METHODS: Plasmid
      p3XFLAG-CMV9-LRIG1 was transfected into neuroglioma cell line H4. Changes of
      LRIG1 and EGFR expression at mRNA and protein levels were measured by RT-PCR and
      Western blot, respectively. Changes of cell proliferation and apoptosis were
      analyzed by MTT and flow cytometry methods. RESULTS: LRIG1 mRNA level in p3XFLAG
      CMV9-LRIG1 transfected H4 cells (1.997+/-0.114) was significantly higher than
      that in control H4 cells (0.500+/-0.031),and p3XFLAG-CMV9 transfected group
      (0.357+/-0.035) (P< 0.001). LRIG1 protein level in p3XFLAG-CMV9-LRIG1 transfected
      H4 cells (1.790+/-0.119) was significantly higher than that in control H4 cells
      (0.717+/-0.038, P< 0.001), and p3XFLAG-CMV9 transfected H4 cells (0.930+/-0.076,
      P=0.001). EGFR mRNA level in p3XFLAG-CMV9-LRIG1 transfected H4 cells (0.463+/
      0.033) was significantly lower than that in control H4 cells (1.157+/-0.067, P<
      0.001), and p3XFLAG-CMV9 transfected H4 cells (0.933+/-0.058, P=0.002). EGFR
      protein level in p3XFLAG-CMV9-LRIG1 transfected H4 cells (0.703+/-0.067) was
      significantly lower than that in control H4 cells (1.280+/-0.078, P=0.003),and
      p3XFLAG-CMV9 transfected H4 cells (1.163+/-0.068,P=0.009). Apoptosis rate in
      LRIG1-transfected H4 cells (18.89%)was lower than that in control H4 cells
      (3.11%), and vector-transfected H4 cells (5.42%, P< 0.001). CONCLUSION: LRIG1
      participates in construction of negative feedback loop of EGFR, which may
      inhibits growth of glioma cells.

PMID- 15473924
TI  - [Mechanism of G2/M cell cycle arrest before apoptosis in leukemia cell line HL-60
      induced by proteasome inhibitor MG132].
AB  - BACKGROUND & OBJECTIVE: Proteasome inhibitor is a kind of potential anti-tumor
      drug,it can induce apoptosis in various tumor cells. This study was designed to
      investigate the molecular mechanism of apoptosis and G(2)/M arrest in leukemia
      cell line HL-60 induced by proteasome inhibitor MG132 (Z-Leu-Leu-Leu-CHO).
      METHODS: Apoptosis in HL-60 cells was observed under fluorescent microscope, flow
      cytometry and immunoblot were used to analyze cell apoptosis, cell cycle arrest,
      and the mechanisms. RESULTS: MG132 (2 micromol/L)induced apoptosis in HL-60 cells
      after 24-h treatment. Meanwhile, HL-60 cells were arrested at G(2)/M phase before
      apoptosis after induced by MG132. The percentage of G(2)/M phase in MG132-treated
      HL-60 cells at 12 h was 63.42+/-2.02,while that in untreated cells was 7.29+/
      3.01 (P< 0.01). The percentage of apoptosis in MG132-treated HL-60 cells at 24 h
      was 16.67+/-1.48, while untreated cells had no death (P< 0.01). Compared to the
      treatment with MG132 only, caffeine (2 mmol/L) exposure can reduce G(2)/M arrest
      and apoptosis in MG132-treated HL-60 cells. Expression of cyclin-dependent kinase
      inhibitor p21waf/cip1 up-regulated after treated with MG132 for 3 h, but no p53
      or p27 detected. CONCLUSIONS: Proteasome inhibitor MG132 can induce G2/M arrest
      before the apoptosis appeared in HL-60 cells. The obvious up-regulation of p21
      indicated that it is p21(waf/cip1), but not p53 or p53-related proteins,that
      involved in the regulation of G(2)/M arrest and subsequent apoptosis induced by
      MG132 in HL-60 cells.

PMID- 15473926
TI  - [Two-dimensional polyacrylamide gel electrophoresis analysis of apoptosis in K562
      cells induced by harringtonine].
AB  - BACKGROUND & OBJECTIVE: Harringtonine (HT),an anti-tumor drug,has been widely
      used to treat acute or chronic myeloid leukemia,and obtained satisfactory
      effects. Studies showed that the anti-tumor activity of HT is related with the
      apoptosis-inducing effect,but the molecular mechanisms remain unclear. This study
      was to analyze the protein maps contributed to the apoptosis in K562 cells
      induced by HT,and to screen the apoptosis-associated proteins. METHODS: Flow
      cytometry was used to distinguish K562 cells of early apoptosis stage from those
      of late apoptosis stage through Annexin V and PI staining. Two-dimensional
      polyacrylamide gel electrophoresis (2-D PAGE) was used to separate and compare
      the HT-induced apoptotic K562 cells and control K562 cells. RESULTS: When K562
      cells were treated with 10 microg/ml HT for 5,a nd 24 hours,percentages of early
      apoptotic cells (Annexin V+/PI-) were 28.3%, and 18.1%(P< 0.01), while
      percentages of late apoptotic cells (Annexin V+/PI+) were 9.1%,and 20.2% (P<
      0.01), respectively. Statistical analysis showed (1300+/-50) protein spots were
      resolved with a match rate of (88.3+/-2.0)% in control K562 cells. Ten protein
      spots in late apoptotic cells displayed changes in expression after induction of
      HT for 24 hours (P< 0.01), of which 8 showed higher expression, 1 decreased,and 1
      only expressed in control k562 cells. CONCLUSION: These proteins may be apoptosis
      associated proteins of K562 cells induced by HT.

PMID- 15473927
TI  - [Detecting protein expression of EphrinB2 ligand and its receptor EphB4 in
      astrocytoma using confocal laser scanning microscopy].
AB  - BACKGROUND & OBJECTIVE: EphrinB2 is a novel angiogenic factor. EphrinB2 and its
      receptor EphB4 express in several kinds of tumor cells,and correlate with
      tumorigenesis and neoangiogenesis. This study was designed to explore the
      characteristics of EphB4 and EphrinB2 protein expression in astrocytomas.
      METHODS: Double labelling immunofluorescence was used to detect co-expression of
      EphB4/EphrinB2 with glial fibrilary acid protein (GFAP)or CD34 protein in 35
      fresh glioma specimens, and 2 kinds of human glioma cell lines (CHG-5,and SHG
      44). RESULTS: EphB4/EphrinB2 and CD34 proteins co-expressed in some tumor stromal
      microvessels, and mainly localizing in endothelial cells. Co-expression of
      EphB4/EphrinB2 and GFAP proteins was also noticed in tumor cells,and 2 glioma
      cell lines. In poorly-differentiated SHG-44 cells, the average fluorescence
      intensity of EphB4 was 72.48+/-33.78,and that of EphrinB2 was 96.80+/-36.98, both
      higher than those in well-differentiated CHG-5 cells (56.7+/-21.7, and 53.6+/
      18.8). But the green fluorescence intensity of GFAP in SHG-44 cells was 22.3+/
      15.3, while in CHG-5 cells was 47.5+/-16.7. CONCLUSION: Expressions of EphB4 and
      EphrinB2 proteins may be related to differentiation degree of tumor cells.

PMID- 15473928
TI  - [Expression of estrogen receptor in different breast cancer cell lines
      transfected with estrogen receptor plasmid HEGO5 mediated by FuGENE6].
AB  - BACKGROUND & OBJECTIVE: Gene transfection is a major approach in studies of
      estrogen receptor (ER)expression in breast cancer cells,and ER's functional
      mechanism. This study was designed to detect the transfection efficiency of
      different human breast cancer cell lines mediated by FuGENE6 reagent, and ER
      expression in these cells after transfected with ER plasmid HEGO5. METHODS:
      Breast cancer cell lines were transfected with plasmid pEGFP-N1,and the
      transfection efficiency was measured by flow cytometry (FCM). The cell lines with
      high transfection efficiency were transfected with HEGO5,and then the expression
      of ER was determined by FCM and Western blot. RESULTS: There were obvious
      differences in transfection efficiencies of breast cancer cell lines MM-231,
      MM330, MM134 VI, MM175VII, MM157, MM361, MM436, MM453, UaCC812, UaCC893, BT-549,
      BT-20, HBL-100, Hs578t, MCF-7, T-47d, and ZR-75-1. Repetitious transfection test
      in HBL-100 cells showed that co-efficient of variation was 5.1. HEGO5 was
      transfected into the cells with high plasmid transfection efficiency (MCF-7, HBL
      100, Hs578t, MM436, MM453, and BT-20), positive rates of ER in these cells ranged
      from 12.9% to 54.8%, corresponding to the pEGFP-N1 transfection efficiency, and
      the expression of ER detected by FCM were in accordance with those tested by
      Western blot. To some extent, the expression of ER in transfected cells was cell
      cycle specific. CONCLUSIONS: Transfection of breast cancer cell lines mediated by
      FuGENE6 reagent has a good repetition,and the results were stable and reliable.
      In the cells transfected with HEGO5,the expression of ER can be qualitatively
      detected by Western blot, and quantitatively detected by FCM.

PMID- 15473929
TI  - [Clinical value of vascular endothelial growth factor detection in forecasting
      distant metastasis risk of nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Vascular endothelial growth factor (VEGF)closely relates
      with the malignancy and metastasis of various kinds of cancers. This study was
      designed to evaluate the value of VEGF detection in forecasting distant
      metastasis risk of nasopharyngeal carcinoma(NPC)patients. METHODS: Tumor
      biopsies,and serum specimens were collected before treatment from 59
      pathologically diagnosed NPC patients, hospitalized in our hospital from Mar.
      1999 to Feb. 2000. Immunohistochemistry LSAB method was used to detect VEGF in
      NPC tissues. VEGF in NPC serum was detected by quantitative enzyme-linked
      immunosorbent assay (ELISA) method. Through follow-up study, the relationship
      between VEGF and distant metastasis of NPC patients was observed. RESULTS: The
      expression of VEGF in NPC tissue,and serum positively related with the distant
      metastasis (P< 0.05). Non-distant metastasis survival rates of different tissue
      VEGF groups were 100%(-), 95.24%(+), 65.19%(++), and 58.93%(+++), significant
      difference existed between every 2 groups (P=0.019 3). Non-distant metastasis
      survival rates of different serum VEGF groups were 82.57% (< 466.78 ng/L), and
      59.11% (>/=466.78 ng/L)(P=0.021 1). Multi-prognostic factors analysis showed that
      VEGF expression in NPC tissue and serum had significant effects on distant
      metastasis of NPC. CONCLUSIONS: The detection of VEGF either in NPC tissue or in
      serum could be regarded as a valuable indicator for predicting distant metastasis
      risk of NPC patients. Combined detection of them could increase the chances of
      forcasting distant metastasis in NPC patients.

PMID- 15473930
TI  - [Expression correlation of Ki67 to P53,VEGF,and C-erbB-2 genes in breast cancer
      and their clinical significances].
AB  - BACKGROUND & OBJECTIVE: The proliferating antigen Ki67 is an important biological
      marker in cell proliferation. This study was designed to investigate the
      expressions of Ki67, P53, vascular endothelial growth factor (VEGF),and C-erbB-2
      in breast cancer tissue, and their correlations with cliniopathological
      significance. METHODS: The expressions of Ki67,p53,VEGF,and C-erbB-2 in 151 cases
      of breast cancer were assessed by immunohisto-chemistry, and their correlations
      with clinicopathological factors were statistically analyzed. RESULTS: The
      positive rate of Ki67 was 78.2%(113/151). The expression of Ki67 correlated with
      tumor stages (P< 0.05), but didn't relate to age, tumor size, and lymph node
      status (P >0.05). In addition,the expression of Ki76 had a positive correlation
      with the expressions of p53, and C-erbB-2 (P< 0.05), but not with the expression
      of VEGF (P >0.05). The co-expression of Ki67 and VEGF related to tumor size,and
      clinical stage (P< 0.05). CONCLUSIONS: The expression of Ki67 is an objective
      biological marker for estimating the occurrence and progression of breast cancer.
      Combined detection of Ki67 and VEGF may helps to judge the clinical stage of
      breast cancer.

PMID- 15473931
TI  - [Utility of SPECT lung perfusion scans in assessing early changes in pulmonary
      function of patients with lung cancer after radiotherapy].
AB  - BACKGROUND & OBJECTIVE: Radiation-induced lung injury is commonly following
      radiotherapy (RT)for tumors in,and around the thorax. Lung function is usually
      assessed by pulmonary function tests (PFTs), but RT-induced regional changes of
      pulmonary function cannot be accurately evaluated by PFTs. Lung perfusion
      scintigraphy compared with other radiographic methods can well assess the
      regional pulmonary physiological function,and 3-dimension conformal radiotherapy
      (3D-CRT) planning system can quantitatively calculate irradiation dosage. This
      study was to assess early changes in the pulmonary function of patients with lung
      cancer receiving thoracic 3D-CRT by lung perfusion scintigraphy. METHODS:
      Nineteen patients receiving thoracic 3D-CRT for lung cancer were studied. Single
      photon emission computed tomography (SPECT) lung perfusion scan,and X-ray or CT
      scan before RT, and after 40-50 Gy radiation were performed. Pre-RT SPECT lung
      perfusion images were classified by comparing lung perfusion defect with area of
      radiological abnormality before RT. Grade 0: no lung perfusion defect in the area
      of radiological abnormality. Grade 1: the size of radiological abnormality is
      similar to the area of lung perfusion defect. Grade 2: the area of lung perfusion
      defect is bigger than that of radiological abnormality,and extend to 1 pulmonary
      lobe. Grade 3: the area of lung perfusion defect exceed 1 pulmonary lobe. The
      radiation field with more than 20 Gy was drawn as a region of interest (ROI). The
      proportion of radioactive count within this ROI to total lung count in one slice
      was calculated to assess changes in pulmonary function after RT. Student's t test
      was used for statistical analyses. RESULTS: All patients had lung perfusion
      defect, 9 patients with grade 1 damage, 5 patients with grade 2 damage, and 5
      patients with grade 3 damage. All tumors in the 19 patients were reduced with
      variant degree after 40-50 Gy radiation in CT or X-ray images. The mean
      radioactive proportions of ROI in 19 patients were (53.7+/-29.8)% before
      radiation,and (57.6+/-22.6)% during RT, the difference wasn't significant
      (P=0.280). The relatively decreased post-RT lung perfusion was observed in 6
      patients, whereas the relatively increased post-RT lung perfusion was observed in
      13 patients. CONCLUSION: SPECT lung perfusion scans is a simple, convenient, and
      useful method for assessing pre-RT regional lung function,and monitoring the
      changes in regional lung function after irradiation.

PMID- 15473932
TI  - [Significance of combining detection of E-cadherin, carcinoembryonic antigen, and
      calretinin in cytological differential diagnosis of serous effusion].
AB  - BACKGROUND & OBJECTIVE: The morphological characteristics of metastatic
      adenocarcinoma cells,malignant mesothelioma cells,and reactive mesothelial cells
      in serous effusions are similar. Sometimes, it is difficult to make a correct
      diagnosis just based on the cytological characteristics. Although now
      immunocytochemistry has been widely used in this field,yet only a few antibodies
      were reported in China,which can't help to make a correct differential diagnosis.
      This study was to evaluate the value of combining detection of E
      cadherin,carcinoembryonic antigen (CEA),and calretinin in cytological
      differential diagnosis of serous effusion. METHODS: A total of 93 effusion
      cytology specimens (66 pleural fluid samples, 24 ascites samples, 3 pericardial
      fluid samples)from 55 cases of metastatic adenocarcinoma, 6 cases of malignant
      mesothelioma, and 32 cases of reactive mesothelium were collected. All cases were
      confirmed histologically or clinically. Materials from each case were prepared in
      HE staining smears,and cell blocks,immunocytochemical staining was performed on
      cell block sections. RESULTS: In diagnosing metastatic adenocarcinoma, the
      sensitivities of E-cadherin, and CEA were 85.5%(47/55), and 79.6% (43/55), the
      specificities were 100% (38/38), and 97.4% (37/38);if E-cadherin and CEA were
      used together,the positive rate was 96.4%(53/55). The sensitivity of calretinin
      for mesothelial cells was 81.6%(31/38),and the specificity was 87.2% (48/55).
      CONCLUSION: The combination of E-cadherin, CEA, and calretinin is a very useful
      antibody panel in cytological differential diagnosis for metastatic
      adenocarcinoma and mesothelial cells in serous effusion.

PMID- 15473933
TI  - [Effect of cyclooxygenase-2,and matrix metalloproteinase-2 expression on
      prognosis of lung cancer].
AB  - BACKGROUND & OBJECTIVE: Expression of cyclooxygenase-2 (COX-2)and matrix
      metalloproteinase-2 (MMP-2)increased in most tumor tissues. Inhibitors of both
      COX-2 and MMP-2 have been experimentally and clinically proved effective against
      the development of tumor. Our study was designed to investigate the expression of
      COX-2 and MMP-2, and the effect of those proteins on lymphoid metastasis and
      prognosis of lung cancer. METHODS: SP immunohistochemistry was used to determine
      the expression of COX-2 and MMP-2 in 42 patients with lung cancer. Kaplan-Meier
      and log-rank test were used to compare the survival time of positive staining
      group and negative staining group. RESULTS: The positive rate of COX-2 was 31%,
      and that of MMP-2 was 62%. The survival time in positive COX-2 group was
      significantly shorter than that in negative COX-2 group (P=0.019). The lymphoid
      metastasis rate of positive MMP-2 group was significantly higher than that of
      negative MMP-2 group (P=0.009). The survival time in positive MMP-2 group was
      significantly shorter than that in negative MMP-2 group (P=0.001). No
      relationship was found between the expression of COX-2 and MMP-2 (P=0.257).
      CONCLUSION: The expression of COX-2 and MMP-2 are closely correlate with the
      prognosis of lung cancer, and the over-expression of those proteins suggest poor
      prognosis in patients with lung cancer.

PMID- 15473934
TI  - [Expression of matrix metalloproteinases-9,2,7,and tissue inhibitor of
      metalloproteinases-1,2,3 mRNA in ovarian tumors and their clinical significance].
AB  - BACKGROUND & OBJECTIVE: Matrix metalloproteinases (MMPs)play an important role in
      cancer cell invasion,and metastasis by degrading the extracellular matrix (ECM).
      The activities of MMPs are regulated by tissue inhibitor of metalloproteinases
      (TIMPs). This study was to detect mRNA expression of MMP-9, 2, 7, and TIMP-1, 2,
      3 in ovarian tumor tissues,and explore their correlations with clinicopathologic
      characteristics,and prognosis of patients with ovarian cancer. METHODS: Reverse
      transcriptase-polymerase chain reaction (RT-PCR)was used to assay the positive
      rates,and half-quantity values of MMP-9, 2, 7, and TIMP-1, 2, 3 mRNA in 48 cases
      of malignant ovarian tumor tissues, 21 cases of benign ovarian tumor tissues, and
      22 cases of normal ovarian tissues. RESULTS: The positive rate of MMP-9 mRNA, and
      the half-quantity values of MMP-9,MMP-2 were significantly higher in malignant
      tumor tissues than those in normal ovarian tissues (P< 0.05). The positive rates
      and half-quantity values of TIMP-2,MMP-7,TIMP-3 mRNA were significantly higher in
      malignant and benign ovarian tumor tissues than those in normal ovarian tissues
      (P< 0.05). The ratio of MMP-9/TIMP-1 was higher in malignant ovarian tumor
      tissues(0.91+/-0.67) than that in normal ovarian tissues (0.14+/-0.33)(P< 0.05).
      The expression level of MMP-9 mRNA was higher in ovarian cancer tissues of stage
      III-IV(1.13+/-0.66) than those of stage I-II(0.60+/-0.54)(P< 0.05). The mean
      survival time of MMP-9 positive patients was (43.00+/-17.12) months,and cumulate
      survival rate was 47.37%,significantly lower than that of MMP-9 negative patients
      (100%). CONCLUSIONS: MMP-9, MMP-2, MMP-7, TIMP-2, TIMP-3 are over-expressed in
      ovarian malignant tissues. The over-expression of MMP-9, and the imbalance
      between MMP-9 and TIMP-1 play important roles in the progress of advanced ovarian
      cancer. MMP-9 may be a useful prognostic marker for patients with advanced
      ovarian cancer.

PMID- 15473935
TI  - [Clinical significance of P53-immunohistochemistry in large slice in evaluating
      distal intramural spread extent in rectal cancer].
AB  - BACKGROUND & OBJECTIVE: The optimal distal molecular clearance margin of rectal
      cancer hasn't been confirmed. This study was designed to explore the molecular
      margin of distal intramural spread (DIS)in rectal cancer, and its prognostic
      value, and to further clarify the required distal margin of radical surgery for
      rectal cancer. METHODS: Sixty-one P53 positive specimens,resected from patients
      with rectal cancer from Aug.1996 to Oct. 1997, were collected. Microscopic DIS
      was examined by P53-immunohistochemistry (P53-IHC),comparing with conventional
      hematoxylineosin (HE)staining in consecutive large slice. Tissue shrinkage
      ratio,comparing the distal clearance margin measured in fresh specimens to that
      measured in large slice after fixed in each case,was used to convert
      macroscopically measured extent of distal spread to its actual extent. After long
      term follow-up, the survival curves of 4 DIS groups were estimated by Life-table
      method. RESULTS: With P53-IHC,DIS was observed in 50 cases (82.0%), DIS extents
      were 0.11-3.50 cm with the mean of 0.59 cm, DIS extent of > 3.00 cm was detected
      in 1 case only. Meanwhile,DIS was observed in 29 cases (47.5%)by HE staining, DIS
      extents were 0.10-1.39 cm with the mean of 0.13 cm. There was significant
      difference between the 2 means (P< 0.0001). The long-term result indicated that
      the survival rate of DIS extent of >1.00 cm group was lower than those of non-DIS
      group,and DIS extent of < 0.50 cm group (P< 0.05). CONCLUSIONS: DIS was more
      exactly detected by P53-IHC than by HE. Most of DIS extents were less than 1 cm
      in rectal cancer. For over 95% cases, 3 cm distal to the rectal cancers was
      relatively safe in radical operations. The poor prognosis can be predicted in
      cases with DIS extent of >1 cm.

PMID- 15473936
TI  - [Correlation of tumor microvessel density to metastasis and recurrence of rectal
      cancer].
AB  - BACKGROUND & OBJECTIVE: Tumor microvessel density (MDV)partly indicates tumor
      angiogenesis,and it is a hot topic in the study of oncology. However, the
      relationship between tumor MVD and the clinicopathological characteristics of
      rectal cancer are unclear. This study was to explore the correlation of tumor MVD
      to metastasis and recurrence of rectal cancer. METHODS: Records of 97 rectal
      cancer patients who had undergone radical resection in the Department of
      Abdominal Surgery, Cancer Center,Sun Yat-sen University from 1996 to 1997 were
      retrospectively analyzed. The paraffin-embedded tissues of resected tumor and
      para-tumor tissues were collected,microvessels were detected by
      immunohistochemistry using mouse anti-human CD31 antibody. The MVD was then
      calculated microscopically, its relations with clinicopathological parameters
      were analyzed with software package of SPSS 9.0. RESULTS: The values of MVD in
      tumor tissues,and non-cancerous para-tumor mucosa were 45.26+/-19.52,and 11.82+/
      3.48 per high magnification field (x400)(P< 0.001). The MVD in the treatment
      failed patients (recurrence and/or metastasis) was 62.72+/-21.75, while it was
      41.23+/-16.68 in the patients with disease-free survival, the difference was
      significant (P< 0.001). CONCLUSIONS: The tumors with higher MVD are more likely
      to relapse or metastasize after operation. Tumor tissue MVD can be used as a
      biological indicator for post-operative metastasis and recurrence in rectal
      cancer.

PMID- 15473937
TI  - [DNA binding activity of nuclear factor-kappa B in human astrocytoma].
AB  - BACKGROUND & OBJECTIVE: Transcription factors of human cancer cells can regulate
      the expression of many malignancy-related gene products,relate to poor
      differentiation,and high metastasis of cancer cells,and also inhibit apoptosis of
      cancer cells. This study was designed to investigate the nuclear factor-kappa B
      (NF-kappaB)DNA binding activity in human astrocytoma tissue,and its significance
      with human astrocytoma development. METHODS: The NF-kappaB DNA binding activities
      of 12 cases of normal brain tissue, and 37 cases of human astrocytoma tissue were
      detected by electrophoretic mobility shift assay (EMSA), and photo densitometry.
      RESULTS: The absorbency of NF-kappaB DNA binding activity in human astrocytoma
      tissue was 134.2+/-24.1, higher than that in normal brain tissue (97.5+/-1.9)(P<
      0.05). The NF-kappaB DNA binding activity in multiform glioblastoma tissue was
      highest (106.8+/-7.4), that in anaplasia Astrocytoma was 123.2+/-10.1, in
      astroblastoma was 139.3+/-16.8,and in astrocytoma was 160.2+/-18.6 (P< 0.05).
      CONCLUSION: The NF-kappaB DNA binding activity correlates with malignancy degree
      of human astrocytoma.

PMID- 15473938
TI  - [Value of 18F-FDG PET imaging in diagnosing tumor residue of intracranial glioma
      after surgery and radiotherapy].
AB  - BACKGROUND & OBJECTIVE: It is difficult to diagnose tumor residue by CT/MRI after
      treatment. The application of (18)F-fluorodeoxyglucose positron emission
      tomography ((18)F-FDG PET) to determine the suspected tumor residue after
      treatment has become a hot target in the study of radiotherapy. This study was
      designed to discuss the clinical value of (18)-FDG PET imaging in post-operative
      and post-radiotherapeutic intracranial glioma. METHODS: (18)F-FDG PET imaging was
      performed in 23 patients with post-operative and post-radio-therapeutic
      intracranial glioma, and compared with CT/MRI. The final diagnosis of tumor
      residue was proved by pathology or clinical follow-up. RESULTS: Of 23 patients,
      12 showed (18)F-FDG PET positive, and 11 showed negative,among which 3 were false
      negative. The accuracy of (18)F-FDG PET was 87.0% (20/23), significantly higher
      than 60.9% (14/23) of CT/MRI scan (P< 0.05). The diagnosis of tumor residue in 9
      patients cannot be determined by CT/MRI, while 4 of these patients showed (18)F
      FDG PET positive, and the other 5 showed (18)F-FDG PET negative. Eight of 23
      patients diagnosed tumor residues by CT/MRI, showed (18)F-FDG PET positive,too.
      Six patients,diagnosed by CT/MRI as radioactive-disease sufferers, and PET
      indicated with low or deficient FDG metabolism, were proved to have radioactive
      diseases by follow-up. CONCLUSIONS: (18)F-FDG PET imaging has significant
      dominance in characterizing lesions,and differentiating tumor residue in post
      operative and post-radiotherapeutic intracranial glioma. Combined with CT and
      MRI, it can provide both anatomical and functional information for treatment.

PMID- 15473939
TI  - [Evaluation of liver reserve function by ICGR15 detection before hepatectomy for
      hepatocellular carcinoma].
AB  - BACKGROUND & OBJECTIVE: Accurate estimation of liver reserve function before
      hepatectomy for liver cancer may avoid postoperative liver failure. Recently,it
      has been considered that indocyanine green retention rate at 15 minutes
      (ICG(R15))can assess liver reserve function with exactitude and high sensitivity.
      This study was to discuss the evaluation of liver cirrhosis severity and liver
      reverse function by ICG(R15), analyze the relationship between ICG(R15) and post
      operative liver failure,and compare ICG(R15) with Child-Pugh grading. METHODS:
      Records of 225 patients with resected hepatocellular carcinoma (HCC)have been
      collected. Pre-operative data, such as a variety of routine liver biochemistry
      tests, Child-Pugh grading, and ICG(R15) value, and intra-operative data, post
      operative data were analyzed. RESULTS: The mean value of ICG(R15) was (9.9+/
      6.2)% in cirrhosis group,and (7.4+/-3.8)% in non-cirrhosis group (P< 0.01). The
      mean value of ICG(R15) was (8.5+/-5.0)% in mild cirrhosis subgroup, (10.7+/-5.7)%
      in moderate cirrhosis subgroup, and (15.8+/-9.6)% in severe cirrhosis subgroup;
      significant differences can be observed while multiple comparisons were performed
      (P< 0.05). The mean values of ICG(R15) in patients who suffered from post
      operative ascites, and jaundice were (11.5+/-6.8)%,and (12.1+/-7.1)%;
      significantly higher than those without ascites, and jaundice [(8.5+/-4.9)%,and
      (9.0+/-5.3)%] (P< 0.05). Possible predictor variables indicating risk factors of
      post-operative complications were entered into a multiple logistic regression
      model, the results showed that ICG(R15) significantly affected the occurrence of
      both post-operative ascites and jaundice (P< 0.05). The mean value of ICG(R15) of
      patients of Child-Pugh B grade was (15.2+/-8.6)%, much higher than that of
      patients of Child-Pugh A grade [(8.8+/-5.1)%](P< 0.01). ICG(R15) values were
      above 10% in 67 of the 212 patients of Child-Pugh A grade, and 6 of these 67
      patients have a value above 20%. CONCLUSIONS: ICG(R15) value rises with the
      aggravation of liver cirrhosis,it affects the occurrence of post-operative liver
      failure significantly. Some correlation can be observed between ICG(R15) and
      Child-Pugh grading.

PMID- 15473940
TI  - [Detection of FLT3 gene and FLT3/ITD gene mutation in chronic myeloid leukemia
      and its significance].
AB  - BACKGROUND & OBJECTIVE: Fms-like tyrosine kinase 3 (FLT3)gene abnormal expression
      could be detected in most of acute myeloid leukemia (AML)patients, and 20%-30% of
      them have FLT3/ITD gene mutation which indicate poor prognosis. This study was to
      detect FLT3 gene expression, and FLT3/ITD gene mutation in chronic myeloid
      leukemia (CML)patients, and analyze their relationships with prognosis. METHODS:
      Polymerase chain reaction (PCR)was used to detect FLT3 gene expression, and
      FLT3/ITD gene mutation in 53 CML patients of chronic phase,and 34 CML patients of
      accelerated phase or blast crisis. RESULTS: FLT3 gene was detected in
      5.7%(3/53)CML patients of chronic phase, and in 55.9% (19/34)CML patients of
      accelerated phase or blast crisis,the difference of FLT3 gene positive rate
      between these 2 groups was significant (P< 0.001). Only 2 of 87 CML patients
      (2.3%)were found with FLT3/ITD mutation. CONCLUSIONS: FTL3 gene expresses mainly
      in CML patients of accelerated phase or blast crisis. FTL3/ITD gene mutation was
      seldom involved in CML patients. The CML patients with FLT3 gene expression and
      FTL3/ITD gene mutation may have poor prognosis.

PMID- 15473941
TI  - [A new applicator with regulatable air bag designed for intracavitary
      brachytherapy of nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Nasopharynx applicator used in intracavitary
      brachytherapy plays an important role in the radiotherapy of nasopharyngeal
      carcinoma (NPC), its quality affects the efficiency of treatment. This study was
      to design a new applicator for clinical use. METHODS: An inexpensive, reusable,
      and flexible latex nasopharynx applicator was designed. An air bag was placed at
      15 mm from the foreside of the applicator, clung to the tube. The edge of air bag
      is tangent to the axis of tube. When the bag was full of air, the tube would
      hunch reversely,close to nasopharyngeal vault. After introduced into nasopharynx
      through middle nasal meatus, the applicator could be fixed in suitable position
      by its rotation, and air bag regulation, and confirmed its position by
      simulation. RESULTS: A total of 221 patients with NPC were treated with external
      beam radiation therapy in our hospital, and boosted HDR brachytherapy using this
      new applicator. The response rate was 92.6% in the primary tumor group (200/216),
      and 100% in the recurrent tumor group (5/5). Mucosal necrosis in the posterior or
      anterior wall of nasopharynx occurred in 5 patients, 8 patients experienced nasal
      congestion and nasal synechia. CONCLUSIONS: This new nasopharynx applicator is
      easy to operate, painless, and well dosage-distributed. Mucosal necrosis is
      likely due to higher fractional dose.

PMID- 15473942
TI  - [Cellar senescence and tumor].
AB  - Cells withdrawing from the cell cycle and entering the terminally non-dividing
      state are referred senescence. With few exceptions,normal cells necessarily enter
      this process. Molecular analyses have identified some changes in gene expressions
      as cells become senescent, including repression of positive-acting
      transcriptional regulators, over-expression of CDK inhibitor, and interference
      with downstream pathways, and changes in telomere and telomerase. Current
      findings show that senescence is well connected with tumorigenesis and tumor
      therapy. Studies with cell types other than fibroblast will better define the
      roles of cellar senescence in tumorigenesis, moreover, it may provide a novel
      therapeutic approach to tumor repression.

PMID- 15473943
TI  - Is dentistry a profession? Part 2. The hallmarks of professionalism.
AB  - In this second in a series of 3 articles, the author builds on the definition of
      professionalism developed in the first article, arguing that the social contract
      between the profession and the public entails a collective responsibility of the
      members of the profession to serve the public good. Several specific professional
      duties are deduced, such as the duties to attain and maintain competence, to
      review one's peers, and to serve all in need of expert care. The third and final
      article will examine whether and to what extent dentistry fulfills these
      responsibilities and outlines some future challenges.

PMID- 15473944
TI  - A macroeconomic review of dentistry in Canada in the 1990s.
AB  - OBJECTIVES: To document the trends in expenditures on dental health care services
      and the number of dental health care professionals in Canada from 1990 to 1999.
      METHODS: Information on dental and health expenditures, numbers of dentists,
      hygienists and dental therapists, and the population of Canada and the provinces
      were obtained from the Canadian Institute for Health Information; data on numbers
      of denturists were obtained from regional bodies and from Health Canada.
      Information on the costs of other disease categories was taken from studies by
      Health Canada (1993 and 1998). International comparisons were made on the basis
      of data published by the Organisation for Economic Co-operation and Development
      (OECD). Indices of change over the decade (in which the 1990 value served as the
      baseline [100]) were calculated. RESULTS: By 1999, the supply of all types of
      dental care providers had increased to 1 for every 904 people. Dental
      expenditures during the 1990s increased by 64% overall and by 49% per capita, a
      rate of increase that exceeded both inflation and costs of health care. Although
      the public share of dental costs decreased from 9.2% to 5.8%, the direct costs of
      dental care increased to rank second (6.30 billion dollars) after those for
      cardiovascular diseases (6.82 billion dollars). Among the OECD nations, Canada
      had the fourth highest per capita dental expenditures and the second lowest per
      capita public dental expenditures. CONCLUSIONS: The direct economic costs of
      dental conditions increased during the 1990s from 4.13 billion dollars to 6.77
      billion dollars. Over the same period, the public share for expenditures on
      dental health care services declined.

PMID- 15473945
TI  - Necrotizing fasciitis of the face: a rare but dangerous complication of dental
      infection.
AB  - Necrotizing fasciitis of the face is extremely rare. However, dentists should be
      familiar with the presentation of this condition because of the suddenness of its
      onset, the rapidity of its spread, the resulting drastically disfiguring
      morbidity and the high rate of mortality associated with it. In this paper, we
      describe the presentation and treatment of a 57-year-old woman with necrotizing
      fasciitis of the face and neck due to dental causes and discuss factors in the
      management of this life-threatening condition.

PMID- 15473948
TI  - Information hidden in signals and macromolecules I. Symbolic time-series
      analysis.
AB  - We describe the conceptual background and practical implementation of some
      recently developed techniques for the analysis of symbol sequences and symbolic
      time series. We emphasize their associated software realization, the WinGramm
      suite of programs, that includes programs for the calculation of conditional
      entropies, context-free grammatical complexity, algorithmic distance and
      redundancy, as well as for the generation of surrogates that preserve symbol
      pairs and triplets. We demonstrate the usefulness of these programs by means of
      two illustrative examples, taken from computational neuroscience. In the first
      one, we obtain evidence of the Markovian character of the cortical inter spike
      intervals of the rat before penicillin treatment, and its disappearance
      afterwards. In the second one, we extend previous investigations about neural
      spike-trains generated by the isolated neuron of the slowly adapting stretch
      receptor organ (SAO), in order to classify sequences of different length of known
      neural behaviors. We include new spike trains, digitized employing the optimal
      partition procedure described by Steuer, Molgedey, Ebeling, & Jimenez-Montano,
      (2001).

PMID- 15473946
TI  - Oral Kaposi's sarcoma in a renal transplant patient: case report and literature
      review.
AB  - Malignancies, including oral Kaposi's sarcoma, may develop in transplant patients
      as a result of immunosuppressive therapy. Both the prevalence and the incidence
      of these malignancies vary. This article describes a renal transplant patient who
      was receiving immunosuppressive therapy and presented with oral Kaposi's sarcoma.
      The lesion was excised and did not recur. However, the patient died as a result
      of viral pneumonitis, secondary to her renal problems. The article also includes
      a review of the literature, with particular emphasis on oral presentation of
      immunosuppression-related malignancies.

PMID- 15473947
TI  - A closer look at diagnosis in clinical dental practice: part 6. Emerging
      technologies for detection and diagnosis of noncaries dental problems.
AB  - The final article of this series examines some recent innovations in diagnostic
      procedures for noncaries dental problems and assesses the potential for new
      endodontic and periodontal methods to become everyday tools of the dental
      clinician.

PMID- 15473949
TI  - The fractal dynamics of self-esteem and physical self.
AB  - The aim of this paper was to determine whether fractal processes underlie the
      dynamics of self-esteem and physical self. Twice a day for 512 consecutive days,
      four adults completed a brief inventory measuring six subjective dimensions:
      global self-esteem, physical self-worth, physical condition, sport competence,
      attractive body, and physical strength. The obtained series were submitted to
      spectral analysis, which allowed their classification as fractional Brownian
      motions. Three fractal analysis methods (Rescaled Range analysis, Dispersional
      analysis, and Scaled Windowed Variance analysis) were then applied on the series.
      These analyses yielded convergent results and evidenced long-range correlation in
      the series. The self-esteem and physical self series appeared as anti-persistent
      fractional Brownian motions, with a mean Hurst exponent of 0.21. These results
      reinforce the conception of self-perception as the emergent product of a
      dynamical system composed of multiple interacting elements.

PMID- 15473950
TI  - Backward and forward-looking expectations in a chaotic cobweb model.
AB  - In this study we research the dynamics shown by a cobweb-type model with linear
      demand, non-invertible supply function and with forward-looking expectations
      associated to backward looking ones. The study of the dynamics exhibited by our
      model will show how the presence of forward-looking expectations represents a
      stabilising factor: As the weight attributed to the above mentioned foreseeing
      form increases, the system becomes less and less complex until it only generates
      orbits converging either to the fixed point or to a cycle-2. It is particularly
      interesting to analyse at the same time the role played by the two forms of
      expectations considered, both of which contribute to market stabilization.

PMID- 15473952
TI  - Splenectomy differentially influences immune responses in various tissue
      compartments of the body.
AB  - Patients without spleens have an increased risk of infection. Previous studies
      have shown that splenectomy (Spx) influences Kupffer cells (KC), peritoneal
      macrophages (pMphi) and alveolar macrophages (aMphi) phagocytosis and
      bactericidal activity. This study examined the effect of Spx on the cytokine
      production by peripheral blood monocular cells (PBMC), KC, aMphi, pMphi and cells
      from mesenteric lymph nodes (MLN). We also determined if Spx influences survival
      following sepsis induced by cecal ligation and puncture (CLP). C57BL/6J male mice
      (8-10 weeks old) underwent sham operation or Spx. Two weeks after sham or Spx,
      KC, pMphi, aMphi, PBMC and cells from MLN were isolated and stimulated with LPS.
      Cell-free supernatants were analyzed for TNF-alpha, IL-6, and IL-10. A
      significant increase in KC, pMphi and aMphi TNF-alpha and IL-6 release was
      observed following Spx. The production of IL-10 was also significantly higher in
      KC under those conditions. In contrast, the release of TNF-alpha, IL-6 and IL-10
      was significantly decreased in PBMC after Spx. Similarly, TNF-alpha and IL-6 was
      also decreased in MLN after Spx. Overall survival after CLP was not different in
      mice subjected to either sham or Spx. However, the mean time to death was
      significantly decreased in mice subjected to Spx compared to sham injured mice.
      These findings suggest that Spx modulates immune cell functions in various tissue
      compartments of the body and results in early deaths following sepsis.

PMID- 15473953
TI  - Overview of interleukin-2 function, production and clinical applications.
AB  - The existence of interleukin (IL)-2 has been recognized for over 25 years, and it
      remains one of the most extensively studied cytokines. Here we present a broad
      overview of IL-2 history, functional activities, biological sources, regulation
      and applications to disease treatment. IL-2 exerts a wide spectrum of effects on
      the immune system, and it plays crucial roles in regulating both immune
      activation and homeostasis. Both IL-2 and its multipartite receptor are
      prototypical of the Type I receptor superfamily, and both have been exploited in
      numerous ways in the clinic. Despite the wealth of information generated about IL
      2 from in vitro culture systems, in vivo mouse knockout models, and clinical
      trials in humans, fascinating new aspects of its functions in the immune system
      continue to emerge.

PMID- 15473954
TI  - Genetic background influences natural killer cell activation during bacterial
      peritonitis in mice, and is interleukin 12 and interleukin 18 independent.
AB  - Some mouse strains produce strong pro-inflammatory, T-helper (Th)1 responses
      (e.g. C57BL/6), or strong anti-inflammatory, Th2 responses (e.g. BALB/c). The
      exact mechanisms for development of distinct immune responses to infection are
      not completely understood, although cytokines such as interleukin (IL)-12, IL-18
      and IL-4 are known to play roles. Natural killer T (NKT)/natural killer (NK)
      cells are important regulators of immune responses in infection and non-infection
      models, and NKT/NK activation is also regulated by IL-12 and IL-18 in many
      models. We investigated the role of IL-12/IL-18 in NKT/NK activation in murine
      bacterial peritonitis, as well as differential NKT and NK cell activation in
      C57BL/6 and BALB/c mice. No differences in NKT or NK cell activation or
      intracellular interferon (IFN)-gamma were determined between mice given control,
      anti-IL-12 or anti-IL-18 antibodies or in NKT/NK cell activation in STAT4-/- mice
      (deficient in IL-12 signaling) or wild type controls. However, there were
      significant differences in the activation of NKT and NK cells between C57BL/6
      mice and BALB/c mice, with NKT/NK cytokine production following Th1 or Th2 lines
      dependent on strain. This suggests a role for NKT and NK cell activation in the
      development of Th1 and Th2 responses during bacterial infection independently of
      IL-12 or IL-18.

PMID- 15473955
TI  - The effect of IL-5 treatment on the stimulation-induced phosphorylation of
      proteins in blood eosinophils.
AB  - Eosinophils are selectively primed and activated by the cytokine IL-5. The aim of
      this investigation was to study the effects of IL-5 treatment on stimulation
      dependent protein phosphorylations, in human peripheral blood eosinophils. After
      IL-5 treatment, basal phosphorylation patterns showed increases in the
      phosphorylation of 67, 80 and 93 kDa proteins. Cell stimulations resulted in the
      following protein phosphorylation increases: 50, 60, 67, 80 and 93 kDa (PMA); 50,
      67, 80 and 93 kDa (STZ); and 67, 80 and 93 kDa (IL-5). The phosphorylation of the
      50 and 60 kDa proteins was shown to be MEK-independent and dependent on some PKC
      isoform/s, whereas that of the 67, 80 and 93 kDa proteins was both MEK- and PKC
      alpha, beta, delta, gamma, tau and zeta-independent. A phosphoprotein of 50 kDa
      was identified as p47(phox) and another of 67 kDa protein as the tyrosine
      phosphatase SHPTP-1. Incubation with IL-5 followed by cell stimulation increased
      the total phosphorylation of p47(phox). Bidimensional (IEF-SDS/PAGE) analysis
      showed that the combination of IL-5 treatment followed by stimulation with either
      PMA or STZ induced the formation of an additional, hyperphosphorylated form of
      p47(phox). The presence of this form would explain the higher NADPH oxidase
      activity normally observed after IL-5 priming.

PMID- 15473957
TI  - Dendritic tiling; new insights from genetics.
AB  - Two papers in the current issues of Neuron (Gallegos and Bargmann) and Cell
      (Emoto et al.) identify a conserved kinase, SAX-1/Trc, and a large protein
      required for Trc activity, SAX-2/Fry, as essential elements in the control of
      dendritic branching and tiling in Drosophila and C. elegans. The tiling and
      ectopic branching phenotypes of trc mutants appear to be independently generated.
      Thus, this kinase is the first signaling protein to be associated specifically
      with tiling.

PMID- 15473958
TI  - Cortical development deNUDEd.
AB  - The development of the cerebral cortex is a highly orchestrated process of cell
      division and migration. In this issue of Neuron, Feng and Walsh and Shu et al.
      examine the roles of two related proteins, Nde1 (mNudE) and Ndel1 (NUDEL), in
      cortical development. These proteins play a crucial role in centrosome
      positioning, with Nde1 functioning mainly during progenitor cell divisions and
      Ndel1 functioning in neuronal migration.

PMID- 15473959
TI  - Peering into the birth canal during ion channel parturition.
AB  - Recent studies have provided detailed structures of the N-terminal T1 domain of
      Kv channel alpha subunits that mediates contranslational subunit assembly. In
      this issue of Neuron, Kosolapov et al. probe T1 domain structure within the
      ribosomal tunnel. They find that the T1 domain forms secondary structure within
      the tunnel, in preparation for its immediate role in governing channel assembly
      upon exit.

PMID- 15473960
TI  - Connecting the dots: from actin polymerization to synapse formation.
AB  - Protrusive behavior of dendritic spines on developing neurons has been previously
      suggested to mediate the formation of new axodendritic synaptic contacts. A study
      by Zito et al. in this issue of Neuron links actin polymerization in dendritic
      spines with the motility that the spines exhibit and the synapses that they form.

PMID- 15473961
TI  - Generation of recognition diversity in the nervous system.
AB  - For decades, it has been suggested that complex neural wiring might be specified
      by extensive diversity in receptor isoforms. Dscam is a cell surface protein with
      38,016 potential alternatively spliced isoforms in the fly nervous system.
      Remarkable binding studies now show that Dscam isoform diversity indeed results
      in an unprecedented level of recognition diversity, showing isoform-specific
      homophilic binding. In vivo studies have begun to suggest models for use of Dscam
      diversity in neuron-target recognition, axon fasciculation, and neuron self
      recognition.

PMID- 15473962
TI  - Cycling the synapse: scenic versus direct routes for vesicles.
AB  - What happens to synaptic vesicles after they release their neurotransmitter
      content? Recent work on a variety of synaptic systems shows that there is no
      single answer to this question. Rather, it seems that neurons use a variety of
      methods to retrieve and reuse synaptic vesicles after they have undergone
      exocytosis. The challenge now is to establish the molecular mechanisms and to
      decipher the rules that govern which cycling pathway is used in a given
      functional context.

PMID- 15473963
TI  - The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model
      of Alzheimer's disease.
AB  - Amyloid beta-peptide (Abeta) accumulation in specific brain regions is a
      pathological hallmark of Alzheimer's disease (AD). We have previously reported
      that a well-characterized acyl-coenzyme A: cholesterol acyltransferase (ACAT)
      inhibitor, CP-113,818, inhibits Abeta production in cell-based experiments. Here,
      we assessed the efficacy of CP-113,818 in reducing AD-like pathology in the
      brains of transgenic mice expressing human APP(751) containing the London (V717I)
      and Swedish (K670M/N671L) mutations. Two months of treatment with CP-113,818
      reduced the accumulation of amyloid plaques by 88%-99% and membrane/insoluble
      Abeta levels by 83%-96%, while also decreasing brain cholesteryl-esters by 86%.
      Additionally, soluble Abeta(42) was reduced by 34% in brain homogenates. Spatial
      learning was slightly improved and correlated with decreased Abeta levels. In
      nontransgenic littermates, CP-113,818 also reduced ectodomain shedding of
      endogenous APP in the brain. Our results suggest that ACAT inhibition may be
      effective in the prevention and treatment of AD by inhibiting generation of the
      Abeta peptide.

PMID- 15473964
TI  - Mechanosensory neurite termination and tiling depend on SAX-2 and the SAX-1
      kinase.
AB  - Mechanosensory neurons provide accurate information about stimulus location by
      restricting their sensory dendrites to nonoverlapping regions, a pattern called
      tiling. Here, we show that C. elegans sax-1 and sax-2 regulate mechanosensory
      tiling by controlling the termination point of sensory dendrites. During
      development, the posterior PLM mechanosensory dendrite overlaps transiently with
      the anterior ALM mechanosensory neuron. This overlap is eliminated during a
      discrete period of paused or slowed PLM process growth, between an early period
      of rapid outgrowth and a later period of maintenance growth. In sax-2 mutants,
      the PLM sensory dendrite fails to slow between the active growth and maintenance
      growth phases, leading to sustained overlap of anterior and posterior
      mechanosensory processes. sax-2 encodes a large conserved protein with
      HEAT/Armadillo repeats that functions with sax-1, an NDR cell morphology
      regulating kinase. High-level expression of sax-2 leads to premature neurite
      termination, suggesting that SAX-2 can directly inhibit neurite growth.

PMID- 15473965
TI  - Short- and long-range attraction of cortical GABAergic interneurons by neuregulin
      1.
AB  - Most cortical interneurons arise from the subcortical telencephalon, but the
      molecules that control their migration remain largely unidentified. Here, we show
      that different isoforms of Neuregulin-1 are expressed in the developing cortex
      and in the route that migrating interneurons follow toward the cortex, whereas a
      population of the migrating interneurons express ErbB4, a receptor for Neuregulin
      1. The different isoforms of Neuregulin-1 act as short- and long-range
      attractants for migrating interneurons, and perturbing ErbB4 function in vitro
      decreases the number of interneurons that tangentially migrate to the cortex. In
      vivo, loss of Neuregulin-1/ErbB4 signaling causes an alteration in the tangential
      migration of cortical interneurons and a reduction in the number of GABAergic
      interneurons in the postnatal cortex. These observations provide evidence that
      Neuregulin-1 and its ErbB4 receptor directly control neuronal migration in the
      nervous system.

PMID- 15473966
TI  - Ndel1 operates in a common pathway with LIS1 and cytoplasmic dynein to regulate
      cortical neuronal positioning.
AB  - Correct neuronal migration and positioning during cortical development are
      essential for proper brain function. Mutations of the LIS1 gene result in human
      lissencephaly (smooth brain), which features misplaced cortical neurons and
      disarrayed cerebral lamination. However, the mechanism by which LIS1 regulates
      neuronal migration remains unknown. Using RNA interference (RNAi), we found that
      the binding partner of LIS1, NudE-like protein (Ndel1, formerly known as NUDEL),
      positively regulates dynein activity by facilitating the interaction between LIS1
      and dynein. Loss of function of Ndel1, LIS1, or dynein in developing neocortex
      impairs neuronal positioning and causes the uncoupling of the centrosome and
      nucleus. Overexpression of LIS1 partially rescues the positioning defect caused
      by Ndel1 RNAi but not dynein RNAi, whereas overexpression of Ndel1 does not
      rescue the phenotype induced by LIS1 RNAi. These results provide strong evidence
      that Ndel1 interacts with LIS1 to sustain the function of dynein, which in turn
      impacts microtubule organization, nuclear translocation, and neuronal
      positioning.

PMID- 15473967
TI  - Mitotic spindle regulation by Nde1 controls cerebral cortical size.
AB  - Ablation of the LIS1-interacting protein Nde1 (formerly mNudE) in mouse produces
      a small brain (microcephaly), with the most dramatic reduction affecting the
      cerebral cortex. While cortical lamination is mostly preserved, the mutant cortex
      has fewer neurons and very thin superficial cortical layers (II to IV). BrdU
      birthdating revealed retarded and modestly disorganized neuronal migration;
      however, more dramatic defects on mitotic progression, mitotic orientation, and
      mitotic chromosome localization in cortical progenitors were observed in Nde1
      mutant embryos. The small cerebral cortex seems to reflect both reduced
      progenitor cell division and altered neuronal cell fates. In vitro analysis
      demonstrated that Nde1 is essential for centrosome duplication and mitotic
      spindle assembly. Our data show that mitotic spindle function and orientation are
      essential for normal development of mammalian cerebral cortex.

PMID- 15473968
TI  - Structure acquisition of the T1 domain of Kv1.3 during biogenesis.
AB  - The T1 recognition domains of voltage-gated K(+) (Kv) channel subunits form
      tetramers and acquire tertiary structure while still attached to their individual
      ribosomes. Here we ask when and in which compartment secondary and tertiary
      structures are acquired. We answer this question using biogenic intermediates and
      recently developed folding and accessibility assays to evaluate the status of the
      nascent Kv peptide both inside and outside of the ribosome. A compact structure
      (likely helical) that corresponds to a region of helicity in the mature structure
      is already manifest in the nascent protein within the ribosomal tunnel. The T1
      domain acquires tertiary structure only after emerging from the ribosomal exit
      tunnel and complete synthesis of the T1-S1 linker. These measurements of ion
      channel folding within the ribosomal tunnel and its exit port bear on basic
      principles of protein folding and pave the way for understanding the molecular
      basis of protein misfolding, a fundamental cause of channelopathies.

PMID- 15473969
TI  - Hair cells require phosphatidylinositol 4,5-bisphosphate for mechanical
      transduction and adaptation.
AB  - After opening in response to mechanical stimuli, hair cell transduction channels
      adapt with fast and slow mechanisms that each depend on Ca(2+). We demonstrate
      here that transduction and adaptation require phosphatidylinositol 4,5
      bisphosphate (PIP(2)) for normal kinetics. PIP(2) has a striking distribution in
      hair cells, being excluded from the basal region of hair bundles and apical
      surfaces of frog saccular hair cells. Localization of a phosphatidylinositol
      lipid phosphatase, Ptprq, to these PIP(2)-free domains suggests that Ptprq
      maintains low PIP(2) levels there. Depletion of PIP(2) by inhibition of
      phosphatidylinositol 4-kinase or sequestration by aminoglycosides reduces the
      rates of fast and slow adaptation. PIP(2) and other anionic phospholipids bind
      directly to the IQ domains of myosin-1c, the motor that mediates slow adaptation,
      permitting a strong interaction with membranes and likely regulating the motor's
      activity. PIP(2) depletion also causes a loss in transduction current. PIP(2)
      therefore plays an essential role in hair cell adaptation and transduction.

PMID- 15473970
TI  - Induction of spine growth and synapse formation by regulation of the spine actin
      cytoskeleton.
AB  - We explored the relationship between regulation of the spine actin cytoskeleton,
      spine morphogenesis, and synapse formation by manipulating expression of the
      actin binding protein NrbI and its deletion mutants. In pyramidal neurons of
      cultured rat hippocampal slices, NrbI is concentrated in dendritic spines by
      binding to the actin cytoskeleton. Expression of one NrbI deletion mutant,
      containing the actin binding domain, dramatically increased the density and
      length of dendritic spines with synapses. This hyperspinogenesis was accompanied
      by enhanced actin polymerization and spine motility. Synaptic strengths were
      reduced to compensate for extra synapses, keeping total synaptic input per neuron
      constant. Our data support a model in which synapse formation is promoted by
      actin-powered motility.

PMID- 15473971
TI  - AMPA receptor-dependent clustering of synaptic NMDA receptors is mediated by
      Stargazin and NR2A/B in spinal neurons and hippocampal interneurons.
AB  - Under standard conditions, cultured ventral spinal neurons cluster AMPA- but not
      NMDA-type glutamate receptors at excitatory synapses on their dendritic shafts in
      spite of abundant expression of the ubiquitous NMDA receptor subunit NR1. We
      demonstrate here that the NMDA receptor subunits NR2A and NR2B are not routinely
      expressed in cultured spinal neurons and that transfection with NR2A or NR2B
      reconstitutes the synaptic targeting of NMDA receptors and confers on exogenous
      application of the immediate early gene product Narp the ability to cluster both
      AMPA and NMDA receptors. The use of dominant-negative mutants of GluR2 further
      showed that the synaptic targeting of NMDA receptors is dependent on the presence
      of synaptic AMPA receptors and that synaptic AMPA and NMDA receptors are linked
      by Stargazin and a MAGUK protein. This system of AMPA receptor-dependent synaptic
      NMDA receptor localization was preserved in hippocampal interneurons but reversed
      in hippocampal pyramidal neurons.

PMID- 15473972
TI  - Unique roles of SK and Kv4.2 potassium channels in dendritic integration.
AB  - Focal activation of glutamate receptors in distal dendrites of hippocampal
      pyramidal cells triggers voltage-dependent Ca(2+) channel-mediated plateau
      potentials that are confined to the stimulated dendrite. We examined the role of
      dendritic K(+) conductances in determining the amplitude, duration, and spatial
      compartmentalization of plateau potentials. Manipulations that blocked SK-type
      Ca(2+)-activated K(+) channels, including apamin and BAPTA dialysis, increased
      the duration of plateau potentials without affecting their amplitude or
      compartmentalization. Manipulations that blocked Kv4.2 A-type K(+) channels,
      including a dominant-negative Kv4.2 construct and 4-aminopyridine, increased the
      amplitude of plateau potentials by allowing them to recruit neighboring
      dendrites. Prolongation of plateau potentials or block of Kv4.2 channels at
      branch points facilitated the ability of dendritic excitation to trigger fast
      action potentials. SK channels thus underlie repolarization of dendritic plateau
      potentials, whereas Kv4.2 channels confine these potentials to single dendritic
      branches, and both act in concert to regulate synaptic integration.

PMID- 15473973
TI  - Activity in posterior parietal cortex is correlated with the relative subjective
      desirability of action.
AB  - Behavioral studies suggest that making a decision involves representing the
      overall desirability of all available actions and then selecting that action that
      is most desirable. Physiological studies have proposed that neurons in the
      parietal cortex play a role in selecting movements for execution. To test the
      hypothesis that these parietal neurons encode the subjective desirability of
      making particular movements, we exploited Nash's game theoretic equilibrium,
      during which the subjective desirability of multiple actions should be equal for
      human players. Behavior measured during a strategic game suggests that monkeys'
      choices, like those of humans, are guided by subjective desirability. Under these
      conditions, activity in the parietal cortex was correlated with the relative
      subjective desirability of actions irrespective of the specific combination of
      reward magnitude, reward probability, and response probability associated with
      each action. These observations may help place many recent findings regarding the
      posterior parietal cortex into a common conceptual framework.

PMID- 15473974
TI  - Neural correlates of behavioral preference for culturally familiar drinks.
AB  - Coca-Cola (Coke) and Pepsi are nearly identical in chemical composition, yet
      humans routinely display strong subjective preferences for one or the other. This
      simple observation raises the important question of how cultural messages combine
      with content to shape our perceptions; even to the point of modifying behavioral
      preferences for a primary reward like a sugared drink. We delivered Coke and
      Pepsi to human subjects in behavioral taste tests and also in passive experiments
      carried out during functional magnetic resonance imaging (fMRI). Two conditions
      were examined: (1) anonymous delivery of Coke and Pepsi and (2) brand-cued
      delivery of Coke and Pepsi. For the anonymous task, we report a consistent neural
      response in the ventromedial prefrontal cortex that correlated with subjects'
      behavioral preferences for these beverages. In the brand-cued experiment, brand
      knowledge for one of the drinks had a dramatic influence on expressed behavioral
      preferences and on the measured brain responses.

PMID- 15473975
TI  - The neural bases of cognitive conflict and control in moral judgment.
AB  - Traditional theories of moral psychology emphasize reasoning and "higher
      cognition," while more recent work emphasizes the role of emotion. The present
      fMRI data support a theory of moral judgment according to which both "cognitive"
      and emotional processes play crucial and sometimes mutually competitive roles.
      The present results indicate that brain regions associated with abstract
      reasoning and cognitive control (including dorsolateral prefrontal cortex and
      anterior cingulate cortex) are recruited to resolve difficult personal moral
      dilemmas in which utilitarian values require "personal" moral violations,
      violations that have previously been associated with increased activity in
      emotion-related brain regions. Several regions of frontal and parietal cortex
      predict intertrial differences in moral judgment behavior, exhibiting greater
      activity for utilitarian judgments. We speculate that the controversy surrounding
      utilitarian moral philosophy reflects an underlying tension between competing
      subsystems in the brain.

PMID- 15473976
TI  - Delivery systems for small molecule drugs, proteins, and DNA: the
      neuroscience/biomaterial interface.
AB  - Manipulation of cellular processes in vivo by the delivery of drugs, proteins or
      DNA is of paramount importance to neuroscience research. Methods for the
      presentation of these molecules vary widely, including direct injection (either
      systemic or stereotactic), osmotic pump-mediated chronic delivery, or even
      implantation of cells engineered to indefinitely secrete a factor of interest.
      Biomaterial-based delivery systems represent an alternative to more traditional
      approaches, with the possibility of increased efficacy. Drug-releasing
      biomaterials, either as injectable microspheres or as three-dimensional implants,
      can deliver a molecule of interest (including small molecule drugs, biologically
      active proteins, or DNA) over a more prolonged period of time than by standard
      bolus injection, avoiding the need for repeated administration. Furthermore,
      sustained-release systems can maintain therapeutic concentrations at a target
      site, thus reducing the chance for toxicity. This review summarizes applications
      of polymer-based delivery of small molecule drugs, proteins, and DNA specifically
      relevant to neuroscience research. We detail the fabrication procedures for the
      polymeric systems and their utility in various experimental models. The
      biomaterial field offers unique experimental tools with downstream clinical
      application for the study and treatment of neurologic disease.

PMID- 15473977
TI  - Bone marrow transplants provide tissue protection and directional guidance for
      axons after contusive spinal cord injury in rats.
AB  - Contusive spinal cord injury (SCI) produces large fluid-, debris- and
      inflammatory cell-filled cystic cavities that lack structure to support
      significant axonal regeneration. The recent discovery of stem cells capable of
      generating central nervous system (CNS) tissues, coupled with success in
      neurotransplantation strategies, has renewed hope that repair and recovery from
      CNS trauma is possible. Based on results from several studies using bone marrow
      stromal cells (MSCs) to promote CNS repair, we transplanted MSCs into the rat SCI
      lesion cavity to further investigate their effects on functional recovery, lesion
      morphology, and axonal growth. We found that transplanted MSCs induced hindlimb
      airstepping--a spontaneous locomotor movement associated with activation of the
      stepping control circuitry--but did not alter the time course or extent of
      overground locomotor recovery. Using stereological techniques to describe spinal
      cord anatomy, we show that MSC transplants occupied the lesion cavity and were
      associated with preservation of host tissue and white matter (myelin),
      demonstrating that these cells exert neuroprotective effects. The tissue matrix
      formed by MSC grafts supported greater axonal growth than that found in specimens
      without grafts. Moreover, uniform random sampling of axon profiles revealed that
      the majority of neurites in MSC grafts were oriented with their long axis
      parallel to that of the spinal cord, suggesting longitudinally directed growth.
      Together, these studies support further investigation of marrow stromal cells as
      a potential SCI repair strategy.

PMID- 15473978
TI  - Transplantation of pig stem cells into rat brain: proliferation during the first
      8 weeks.
AB  - Previous work indicated that pig umbilical cord matrix (pUCM) cells are a type of
      primitive stem cell and that these cells could be recovered after central or
      peripheral injection into rats that did not receive immune suppression therapy.
      To determine the safety and proliferation potential of pUCM cells after brain
      transplantation, approximately 150 pUCM cells were transplanted into the brains
      of rats that previously received a striatal injection of the neurotoxin 6
      hydroxydopamine (6-OHDA). The pUCM cells were previously engineered to express
      enhanced green fluorescent protein (eGFP); in this way, the graft cells were
      identified. The rats did not receive immune suppression therapy. There were no
      postsurgical complications and the animals thrived following transplantation. At
      2, 4, 6, and 8 weeks after transplantation, two rats were sacrificed and the
      morphology, size and number of graft cells, and the percentage of tyrosine
      hydroxylase (TH)-positive graft cells were determined. The size distribution of
      the grafted pUCM cells was unimodal and normal, and the average size increased
      significantly over the 2- to 8-week survival period. The number of pUCM cells
      increased from approximately 5400 cells at the 2-week survival period post
      transplantation to approximately 20,000 cells at the 8-week survival period.
      There was an increase in the percentage of TH-positive pUCM cells from
      approximately 1% at the 2-week survival period to approximately 6% at the 8-week
      survival period. There was no evidence of a significant host immune response at
      any time; for example, no accumulation of CD-4, CD-8, CD-11b, CD-161 cells in the
      transplantation site. These results suggest that pUCM cells engraft and
      proliferate without requiring immune suppression. These findings also suggest
      that a subset of pUCM cells can differentiate into TH-positive cells within 8
      weeks after transplantation into the 6-OHDA lesioned rat brain.

PMID- 15473979
TI  - Induction of GABAergic phenotype in a neural stem cell line for transplantation
      in an excitotoxic model of Huntington's disease.
AB  - The implementation of cell replacement therapies for Huntington's disease using
      multipotent neural stem cells (NSCs) requires the specific differentiation into
      gamma-aminobutyric acid (GABA) neuronal subtype before transplantation. Here we
      present an efficient culture procedure that induces stable GABAergic neurons from
      the immortalized striatal neural stem cell line ST14A. This process requires
      sequential retinoic acid treatment and KCl depolarization. Initial addition of 10
      microM retinoic acid increased cell survival and promoted neuronal
      differentiation. Subsequent stimulation with 40 mM KCl induced specific
      differentiation into GABAergic neurons, yielding 74% of total cultured cells. KCl
      evoked Ca(2+) influx reduced cell proliferation and nestin expression, and
      induced neurite outgrowth and GABAergic markers as well as GABA contents,
      release, and uptake. Characterization of the integration, survival, and phenotype
      of these predifferentiated GABAergic neurons following transplantation into the
      adult brain in a model of Huntington's disease revealed long-term survival in
      quinolinate-lesioned striata. Under these conditions, cells maintained their
      GABAergic phenotype and elaborated neurite processes with synaptic contacts with
      endogenous neurons. In conclusion, we have generated a homogeneous population of
      functional GABAergic neurons from a neural stem cell line, which survive and
      maintain their acquired fate in vivo. These data may lend support to the
      possibility of cell replacement therapies for Huntington's disease using neural
      stem cells.

PMID- 15473980
TI  - Impaired axonal transport and altered axolemmal permeability occur in distinct
      populations of damaged axons following traumatic brain injury.
AB  - Traumatic axonal injury (TAI) evolves within minutes to hours following traumatic
      brain injury (TBI). Previous studies have identified axolemmal disruption and
      impaired axonal transport (AxT) as key mechanisms in the evolution of TAI. While
      initially hypothesized that axolemmal disruption culminates in impaired AxT,
      previous studies employed single-label methodologies that did not allow for a
      full determination of the spatial-temporal relationships of these two events. To
      explore directly the relationship between impaired AxT and altered axolemmal
      permeability, the current investigation employed 40, 10, and 3 kDa fluorescently
      conjugated dextrans as markers of axolemmal integrity, with antibodies targeting
      the anterogradely transported amyloid precursor protein (APP) utilized as a
      marker of impaired AxT. Rats underwent impact acceleration TBI and were
      intrathecally administered 40 kDa, 40 + 10 kDa or 40 + 3 kDa fluorescently tagged
      dextrans, with brains subsequently prepared for APP immunofluorescence. Brainstem
      corticospinal tracts (CSpT), medial lemnisci (ML), and medial longitudinal
      fasciculi were examined for evidence of TAI. APP and all dextrans consistently
      localized to distinct classes of TAI. Dextrans were noted as early as 5 min
      following injury within axonal segments demonstrating an irregular/tortuous
      appearance, and were seen within thin and elongate/vacuolated axons by 30 min-6 h
      following injury. APP, first noted within swollen axons at 30 min following
      injury, was found within progressively swollen axons that showed no dextran
      colocalization within 3 h of injury. However, by 6 h, dextrans colocalized in
      disconnected axonal bulbs. At this time-point, dextrans also persisted within
      single-labeled, highly vacuolated/thin, and elongate axons. These studies confirm
      that axolemmal disruption and impaired AxT occur as distinct non-related events
      early in the pathogenesis of TAI. Further, these studies provide evidence that
      the process of impaired axonal transport and subsequent axonal disconnection
      leads to delayed axolemmal instability, rather than proceeding as a consequence
      of initial axolemmal failure. This finding underscores the need of multiple
      approaches to fully assess the axonal response to TBI.

PMID- 15473981
TI  - Neuroprotection in the rat lateral fluid percussion model of traumatic brain
      injury by SNX-185, an N-type voltage-gated calcium channel blocker.
AB  - Overload of intracellular calcium ([Ca(2+)](i)) following traumatic brain injury
      (TBI) has been implicated in the pathogenesis of neuronal injury and death.
      Voltage-gated calcium channels (VGCCs) provide one of the major sources of Ca(2+)
      entry into cells. Therefore, the potential neuroprotective activity of SNX-185, a
      specific N-type VGCC blocker, was tested in rats using the lateral fluid
      percussion (LFP) model of TBI. SNX-185 (50, 100, or 200 pmol) or vehicle was
      injected 5 min after injury into the CA2-3 subregion of the hippocampus
      ipsilateral to TBI. Acute neuronal degeneration was visualized in brain sections
      24 h postinjury using the histofluorescent marker Fluoro-Jade (FJ), and the
      number of surviving neurons in the CA2-3 subregion of the hippocampus 42 days
      after injury was determined stereologically. Behavioral outcome after TBI and
      drug treatment was assessed in the beam walk test and Morris water maze. Direct
      injection of SNX-185 into the CA2-3 region of the hippocampus reduced neuronal
      injury 24 h after TBI and increased neuronal survival at 42 days at each of the
      three drug concentrations. Behavioral outcome in both the beam walk and Morris
      water maze were also improved by SNX-185, with 100 and 200 pmol, but not 50 pmol
      SNX-185 providing neuroprotection. These data support previous studies
      demonstrating substantial neuroprotection after TBI by treatment with N-type VGCC
      blockers.

PMID- 15473982
TI  - Genetic analysis of inherited hydrocephalus in a rat model.
AB  - Congenital hydrocephalus is a serious neurological disorder with a diverse
      etiology. Although there is strong evidence for genetic causes, few genes have
      been identified in humans. The rodent model, the H-Tx rat, has hydrocephalus with
      an onset in late gestation and a complex mode of inheritance. Ventricular
      dilatation is associated with abnormalities in the cerebral aqueduct and
      subcommissural organ. Quantitative trait locus (QTL) mapping was performed on DNA
      from the progeny of a backcross with the non-hydrocephalic Fischer F344 strain,
      using DNA microsatellite markers. The hydrocephalus trait was quantified by
      measuring the severity of the ventricular dilatation. Four chromosomes, each with
      a locus for hydrocephalus (Chrs 9, 10, 11, and 17), were mapped using additional
      markers and DNA from four subsets of backcross progeny with allelic recombination
      at or near each locus. The genetic positions for the markers and the loci were
      located using the Ensemble Rat Genome Browser. For each chromosome studied, the
      interval containing the locus was examined for known rat genes and for human
      genes identified from human-rat homology. Genes expressed in brain and with a
      function associated with known causes of hydrocephalus were identified as
      possible candidate genes. Future studies to characterize the causative genes in
      this animal model will improve the understanding of genetic causes in humans.

PMID- 15473983
TI  - Enhanced release of synaptic glutamate underlies the potentiation of oxygen
      glucose deprivation-induced neuronal injury after induction of NOS-2.
AB  - Reactive nitrogen oxide species (RNOS) may contribute to the
      progression/enhancement of ischemic injury by augmentation of glutamate release,
      reduction of glutamate uptake, or a combination of both. Consistent with this,
      induction of nitric oxide synthase (NOS-2) in murine neocortical cell cultures
      potentiated neuronal cell death caused by combined oxygen-glucose deprivation in
      association with a net increase in extracellular glutamate accumulation. However,
      uptake of glutamate via high affinity, sodium-dependent glutamate transporters
      was unimpaired by induction of NOS-2 under either aerobic or anaerobic
      conditions. Further, blocking possible routes of extra-synaptic glutamate release
      with NPPB [5-nitro-2-(3-phenylpropylamino)-benzoic acid], a volume-sensitive
      organic anion channel blocker, or TBOA (d,l-threo-beta-benzyloxyaspartate), an
      inhibitor of glutamate transport, exacerbated rather than ameliorated injury.
      Finally, treatment with riluzole or tetanus toxin attenuated the enhancement in
      both glutamate accumulation and oxygen-glucose deprivation-induced neuronal
      injury supporting the idea that increased synaptic release of glutamate
      underlies, at least in part, the potentiation of neuronal injury by RNOS after
      NOS-2 induction.

PMID- 15473984
TI  - Motor response to amphetamine treatment, task-specific training, and limited
      motor experience in a postacute animal stroke model.
AB  - Despite advances in acute treatment of ischemic cerebrovascular events, the most
      common clinical outcome is disabling neurological impairment. Despite
      experimental evidence that psychostimulant treatment can positively affect
      recovery rate after focal brain lesions, beyond rehabilitation therapies there
      are no currently accepted medical treatments indicated for diminishing
      neurological impairment after clinically established stroke. To test the effect
      of amphetamine, task-specific training, limiting motor experience, and their
      interaction on motor recovery in a postacute animal model of stroke, animals were
      nonaversively trained in beam walking before a unilateral photochemical
      sensorimotor cortex lesion and tested for 10 days after lesion. Animals were
      randomized to groups receiving: a single session of motor training 24 h after
      lesion; a single injection of amphetamine 2 mg/kg 24 h after lesion; beam-walking
      experience limited to testing on days 1 and 10 after lesion; and groups that
      received amphetamine treatment combined with training or combined with limited
      experience. Motor recovery was maximally enhanced by training, delayed by
      amphetamine treatment, and most negatively affected by limiting beam-walking
      experience during the recovery period. These findings support physical training
      after stroke, indicating that limiting physical activity negatively affects motor
      recovery and raises questions about the role of stimulant treatment to enhance
      motor recovery in the postacute phase after stroke.

PMID- 15473985
TI  - SVZa neural stem cells differentiate into distinct lineages in response to BMP4.
AB  - Neural stem cells (NSCs) reside in the anterior portion of the forebrain
      subventricular zone (SVZa) and generate the progenitors which will differentiate
      into neurons, and via a tangential migratory pathway, known as the rostral
      migratory stream (RMS), migrate to the olfactory bulbs (OB). Bone morphogenetic
      proteins (BMPs) play significant roles in neural development at different stages
      and locations, but their roles have not been determined in the SVZa. To explore
      possible roles of BMPs in SVZa NSCs, BMP4 at various concentrations were tested
      for their capacity to induce SVZa NSCs. The expression of BMP4 was also examined
      in living cells using a reportor vector, in which the BMP4 promotor was
      conjugated with red fluorescent protein (RFP). In the meantime, the
      differentiation of SVZa NSCs was dynamically monitored by using reportor vectors
      of the Nestin enhancer and the promoters of TH and GFAP. In the OB, high
      expression of BMP4 was found using both promoter activity analysis and in situ
      hybridization. However, low BMP4 expression was found in the RMS and only
      moderate expression of BMP4 was displayed in the SVZa. The results also
      demonstrated that low concentrations (1-5 ng/ml) of BMP4 promoted the
      proliferation of SVZa NSCs but high concentrations (10-100 ng/ml) of BMP4
      inhibited this proliferation. BMP4 enhanced neuron commitment before 4 days but
      inhibited it after 4 days. As the antagonist of BMP4, Noggin almost completely
      blocked all these BMP4 responses. Thus, our findings indicate that BMP4 promotes
      the exit from the cell cycle and triggers the differentiation of neuron
      progenitors in the OB. BMP4 also promotes the proliferation of the committed
      neuron progenitors in the RMS, but in the SVZa, BMP4 may facilitate the
      commitment of NSCs into astrocytes.

PMID- 15473986
TI  - Region-specific cell grafting into cervical and lumbar spinal cord in rat: a
      qualitative and quantitative stereological study.
AB  - In the present study, we have characterized an atraumatic grafting technique
      which permits multiple, segmental, and lamina-specific injections into cervical
      or lumbar spinal cord. Cell injections were performed in spinally mounted rats of
      different ages and spinal cord size, using a micromanipulator and glass
      microcapillary connected to a digital microinjector. For grafting, we used human
      neuroteratoma (hNT) cells, BrdU-labeled rat spinal precursors or primary
      embryonic spinal cord neurons isolated from E14 spinal cord of the eGFP+ rat.
      Systematic quantification of grafted cells was performed using stereological
      principles of systematic random sampling and semi-automated optical Disector
      software. Volume reconstruction was performed using serial sections from grafted
      areas and custom-developed software (Ellipse) which permits "two reference
      points" semi-automated alignment of images, as well as volume reconstruction and
      calculation. By coupling these techniques, it is possible to achieve a relatively
      precise and atraumatic cell delivery into multiple spinal cord segments and
      specific spinal laminae. Consistency of the multiple grafts position in the
      targeted laminar areas was verified by a systematic volume reconstruction. Good
      survival of implanted cells for the three different cell lines used indicate that
      this grafting technique coupled with a systematic analysis of the individual
      grafting sites can represent a valuable implantation-analytical system.

PMID- 15473987
TI  - Pyridoxine-induced toxicity in rats: a stereological quantification of the
      sensory neuropathy.
AB  - Excess ingestion of pyridoxine (vitamin B6) causes a severe sensory neuropathy in
      humans. The mechanism of action has not been fully elucidated, and studies of
      pyridoxine neuropathy in experimental animals have yielded disparate results.
      Pyridoxine intoxication appears to produce a neuropathy characterized by necrosis
      of dorsal root ganglion (DRG) sensory neurons and degeneration of peripheral and
      central sensory projections, with large diameter neurons being particularly
      affected. The major determinants affecting the severity of the pyridoxine
      neuropathy appear to be duration and dose of pyridoxine administration,
      differential neuronal vulnerability, and species susceptibility. The present
      study used design-based stereological techniques in conjunction with
      electrophysiological measures to quantify the morphological and physiological
      changes that occur in the DRG and the distal myelinated axons of the sciatic
      nerve following pyridoxine intoxication. This combined stereological and
      electrophysiological method demonstrates a general approach that could be used
      for assessing the correlation between pathophysiological and functional
      parameters in animal models of toxic neuropathy.

PMID- 15473988
TI  - Astroglial plasticity and glutamate function in a chronic mouse model of
      Parkinson's disease.
AB  - Astrocytes play a major role in maintaining low levels of synaptically released
      glutamate, and in many neurodegenerative diseases, astrocytes become reactive and
      lose their ability to regulate glutamate levels, through a malfunction of the
      glial glutamate transporter-1. However, in Parkinson's disease, there are few
      data on these glial cells or their regulation of glutamate transport although
      glutamate cytotoxicity has been blamed for the morphological and functional
      decline of striatal neurons. In the present study, we use a chronic mouse model
      of Parkinson's disease to investigate astrocytes and their relationship to
      glutamate, its extracellular level, synaptic localization, and transport. C57/bl
      mice were treated chronically with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      and probenecid (MPTP/p). From 4 to 8 weeks after treatment, these mice show a
      significant loss of dopaminergic terminals in the striatum and a significant
      increase in the size and number of GFAP-immunopositive astrocytes. However, no
      change in extracellular glutamate, its synaptic localization, or transport
      kinetics was detected. Nevertheless, the density of transporters per astrocyte is
      significantly reduced in the MPTP/p-treated mice when compared to controls. These
      results support reactive gliosis as a means of striatal compensation for dopamine
      loss. The reduction in transporter complement on individual cells, however,
      suggests that astrocytic function may be compromised. Although reactive
      astrocytes are important for maintaining homeostasis, changes in their ability to
      regulate glutamate and its associated synaptic functions could be important for
      the progressive nature of the pathophysiology associated with Parkinson's
      disease.

PMID- 15473989
TI  - Involvement of dopamine D(2)/D(3) receptors and BDNF in the neuroprotective
      effects of S32504 and pramipexole against 1-methyl-4-phenylpyridinium in
      terminally differentiated SH-SY5Y cells.
AB  - Anti-parkinsonian agents possessing both D(2) and D(3) receptor agonist
      properties are neuroprotective against 1-methyl-4-phenylpyridinium (MPP(+))
      toxicity in a variety of in vitro models. The mechanisms underlying protection by
      these D(2)/D(3) receptor agonists remain poorly defined. To test if the D(3)
      receptor preferring agonists S32504 and pramipexole act through D(2) or D(3)
      receptors and via brain-derived neurotrophic factor (BDNF)-dependent pathways, we
      utilized a terminally differentiated neuroblastoma SH-SY5Y cell line exhibiting a
      dopaminergic phenotype. The cytotoxic effects of MPP(+) (LD(50) of 100 microM)
      were stereospecifically antagonized by S32504 (EC(50) = 2.0 microM) and, less
      potently, by pramipexole (EC(50) = 64.3 microM), but not by their inactive
      stereoisomers, R(+) pramipexole and S32601, respectively. Neuroprotective effects
      afforded by EC(50) doses of S32504 and pramipexole were antagonized by the
      selective D(3) antagonists S33084, U99194A, and SB269652, and by the D(2)/D(3)
      antagonist raclopride. However, the preferential D(2) receptor antagonist
      LY741626 was ineffective as was the D1 antagonist SCH23390. BDNF (1 nM) potently
      protected against MPP(+)-induced neurotoxicity. Antibody directed against BDNF
      concentration-dependently blocked both the neuroprotective effects of BDNF and
      those of pramipexole and S32504 against MPP(+). The protection afforded by BDNF
      was blocked by the P3K-AKT pathway inhibitor LY249002 and less so by the
      MEK/MAPKK pathway inhibitor PD98059. LY249002, but not PD98059, blocked the
      neuroprotective effects of pramipexole and S32504 against MPP(+) toxicity. In
      conclusion, S32504 and, less potently, pramipexole show robust, stereospecific,
      and long-lasting neuroprotective effects against MPP(+) toxicity that involve
      D(3) receptors. Their actions also reflect downstream recruitment of BDNF and via
      a PK3-AKT pathway.

PMID- 15473990
TI  - Bladder and urethral sphincter responses evoked by microstimulation of S2 sacral
      spinal cord in spinal cord intact and chronic spinal cord injured cats.
AB  - Urinary bladder and urethral sphincter responses evoked by bladder distention,
      ventral root stimulation, or microstimulation of S2 segment of the sacral spinal
      cord were investigated under alpha-chloralose anesthesia in cats with an intact
      spinal cord and in chronic spinal cord injured (SCI) cats 6-8 weeks after spinal
      cord transection at T9-T10 spinal segment. Both SCI and normal cats exhibited
      large amplitude reflex bladder contractions when the bladder was fully distended.
      SCI cats also exhibited hyperreflexic bladder contractions during filling and
      detrusor-sphincter dyssynergia during voiding, neither was observed in normal
      cats. Electrical stimulation of the ventral roots revealed that the S2 sacral
      spinal cord was the most effective segment for evoking large amplitude bladder
      contractions or voiding in both types of cats. Microstimulation with a stimulus
      intensity of 100 microA and duration of 30-60 s via a single microelectrode in
      the S2 lateral ventral horn or ventral funiculus evoked large amplitude bladder
      contractions with small urethral contractions in both normal and SCI cats.
      However, this stimulation evoked incomplete voiding due to either co-activation
      of the urethral sphincter or detrusor-sphincter dyssynergia. Stimulation in the
      S2 dorsal horn evoked large amplitude sphincter responses. The effectiveness of
      spinal cord microstimulation with a single electrode to induce prominent bladder
      and urethral sphincter responses in SCI animals demonstrates the potential for
      using microstimulation techniques to modulate lower urinary tract function in
      patients with neurogenic voiding dysfunctions.

PMID- 15473991
TI  - Quantitative assessment of deficits and recovery of forelimb motor function after
      cervical spinal cord injury in mice.
AB  - A large proportion of spinal cord injuries (SCIs) in humans are at the cervical
      (C) level, but there are few tests to quantitatively assess forelimb motor
      function after cervical spinal cord injury in rodents. Here, we describe a simple
      and reliable technique for assessing forelimb grip strength over time. Female
      C57Bl/6 mice were trained on the Grip Strength Meter (GSM, TSE-Systems), then
      received a lateral hemisection of the spinal cord at level C5, C6, C7, or T1.
      Gripping ability by each forepaw was then tested for 4 weeks postinjury. Before
      injury, there was no significant difference in the force exerted by either
      forepaw. After hemisections at C5, C6, or C7, the forepaw ipsilateral to the
      injury was initially completely unable to grip (day 2 postinjury), and there was
      a slight transient decrease in the strength of the contralateral paw compared to
      presurgical levels. The ipsilateral forepaw exhibited no ability to grip until
      about 10-14 days postlesion, at which time grip reappeared and strength then
      recovered over a period of a few days to a level that was about 50% of preinjury
      levels. Grip strength was minimally and transiently affected by hemisection at
      T1. The grip strength analysis provides a convenient, quantitative measure of the
      loss and recovery of forelimb function after cervical injury.

PMID- 15473992
TI  - Alzheimer's pathology in human temporal cortex surgically excised after severe
      brain injury.
AB  - Traumatic brain injury (TBI) is a risk factor for the development of Alzheimer's
      disease (AD). This immunohistochemical study determined the extent of AD-related
      changes in temporal cortex resected from individuals treated surgically for
      severe TBI. Antisera generated against Abeta species (total Abeta, Abeta(1-42),
      and Abeta(1-40)), the C-terminal of the Abeta precursor protein (APP),
      apolipoprotein E (apoE), and markers of neuron structure and degeneration (tau,
      ubiquitin, alpha-, beta-, and gamma-synuclein) were used to examine the extent of
      Abeta plaque deposition and neurodegenerative changes in 18 TBI subjects (ages 18
      64 years). Diffuse cortical Abeta deposits were observed in one third of subjects
      (aged 35-62 years) as early as 2 h after injury, with only one (35-year old)
      individual exhibiting "mature", dense-cored plaques. Plaque-like deposits,
      neurons, glia, and axonal changes were also immunostained with APP and apoE
      antibodies. In plaque-positive cases, the only statistically significant change
      in cellular immunostaining was increased neuronal APP (P = 0.013). There was no
      significant correlation between the distribution of Abeta plaques and markers of
      neuronal degeneration. Diffuse tau immunostaining was localized to neuronal cell
      soma, axons or glial cells in a larger subset of individuals. Tau-positive,
      neurofibrillary tangle (NFT)-like changes were detected in only two subjects,
      both of more advanced age and who were without Abeta deposits. Other
      neurodegenerative changes, evidenced by ubiquitin- and synuclein-immunoreactive
      neurons, were abundant in the majority of cases. Our results demonstrate a
      differential distribution and course of intra- and extra-cellular AD-like changes
      during the acute phase following severe TBI in humans. Abeta plaques and early
      evidence of neuronal degenerative changes can develop rapidly after TBI, while
      fully developed NFTs most likely result from more chronic disease- or injury
      related processes. These observations lend further support to the hypothesis that
      head trauma significantly increases the risk of developing pathological and
      clinical symptoms of AD, and provide insight into the molecular mechanisms that
      initiate these pathological cascades very early during severe brain injury.

PMID- 15473993
TI  - Combination therapy of moderate hypothermia and thrombolysis in experimental
      thromboembolic stroke--an MRI study.
AB  - Thrombolysis (T) is limited by reperfusion-associated injury and the short
      therapeutic window after stroke onset. The present study investigates whether
      hypothermia alone or in combination with thrombolysis has beneficial effects
      after experimental thromboembolic stroke. Wistar rats (n = 60) were subjected to
      thromboembolic occlusion (TE) of the middle cerebral artery (MCA). Thrombolysis
      (T) was performed with intravenous recombinant tissue-plasminogen activator (rt
      PA) 1 h (early T) or 3 h (late T) after TE. Hypothermia (Hy) was applied for 4 h
      at 33 degrees C started 1 h after TE. Experimental groups included control (C),
      early thrombolysis (ET), late thrombolysis (LT), hypothermia (Hy), early
      thrombolysis plus hypothermia (ET+Hy), and late thrombolysis plus hypothermia
      (LT+Hy). Animals were investigated by MRI and silver infarct staining (SIS) to
      assess the cerebral infarct size. All animals of group Hy survived, in contrast
      to 40% in group C (P < 0.05). ET+HY and LT+Hy showed a trend towards better
      survival as compared to ET and LT alone. PWI parameters were not significantly
      different between ET versus ET+HY and LT versus LT+Hy, but rt-PA administration
      led to improved cerebral perfusion in MRI. Significant differences in infarct
      volumes (T2/SIS) were found after 24 h in all treatment groups versus the control
      group (P < 0.05). The lesion volume calculated from T2 was significantly smaller
      in ET (16% +/- 5%), ET+Hy (10 +/- 4%), and LT+Hy (20% +/- 9%) after 5.5 h (10.8%
      +/- 4.8%) versus C (42% +/- 15%), (P < 0.05). These data indicate that
      hypothermia improves survival and decreases infarct volume. However, there were
      no significant differences between the use of rt-PA alone or in combination with
      hypothermia. Further studies are needed to confirm these effects, also several
      days after stroke onset.

PMID- 15473994
TI  - Early abnormalities in sciatic nerve function and structure in a rat model of
      Charcot-Marie-Tooth type 1A disease.
AB  - We investigated early peripheral nervous system impairment in PMP22-transgenic
      rats ("CMT rat"), an established animal model for Charcot-Marie-Tooth disease 1A,
      at postnatal day 30 (P30), when the clinical phenotype is not yet apparent.
      Hemizygous CMT1A rats and wildtype littermates were studied by means of
      behavioral examination, electrophysiology, molecular biology, and light
      microscopy analysis. Behavioral studies only showed, a mild, but significant,
      decrease in toe spread 1-5, suggesting a weakness of distal foot muscles in CMT1A
      rats compared with normal littermates. Nerve conduction studies disclosed a
      severe slowing in motor conduction velocity, a temporal dispersion and a dramatic
      decrease of amplitude of motor waves in P30 transgenic animals. Coherently with a
      demyelinating process, affected nerves showed a significant thinning of myelin.
      Interestingly, axonal diameter and area were unchanged, but expression of non
      phosphorylated neurofilaments was increased in CMT1A rats compared with normal
      controls. Our results confirm the fidelity of this animal model to human disease.
      Similarly, in young CMT1A patients, the MCV is significantly reduced and the
      muscle weakness is confined to distal segments, whereas morphological and
      morphometrical signs of axonal atrophy are absent. However, the presence of a
      molecular and functional damage of the axons suggests that this may be the
      correct moment to start neuroprotective therapies.

PMID- 15473995
TI  - Differential vulnerability of immature murine neurons to oxygen-glucose
      deprivation.
AB  - In vivo studies support selective neuronal vulnerability to hypoxia-ischemia (HI)
      in the developing brain. Since differences in intrinsic properties of neurons
      might be responsible, pure cultures containing immature neurons (6-8 days in
      vitro) isolated from mouse cortex and hippocampus, regions chosen for their
      marked vulnerability to oxidative stress, were studied under in vitro ischemic
      conditions-oxygen-glucose deprivation (OGD). Twenty-four hours of reoxygenation
      after 2.5 h of OGD induced significantly greater cell death in hippocampal than
      in cortical neurons (67.8% vs. 33.4%, P = 0.0068). The expression of neuronal
      nitric oxide synthase (nNOS) protein, production of nitric oxide (NO), and
      reactive oxygen species (ROS), as well as glutathione peroxidase (GPx) activity
      and intracellular levels of reduced glutathione (GSH), were measured as
      indicators of oxidative stress. Hippocampal neurons had markedly higher nNOS
      expression than cortical neurons by 24 h of reoxygenation, which coincided with
      an increase in NO production, and significantly greater ROS accumulation. GPx
      activity declined significantly in hippocampal but not in cortical neurons at 4
      and 24 h after OGD. The decrease in GSH level in hippocampal neurons correlated
      with the decline of GPx activity. Our data suggest that developing hippocampal
      neurons are more sensitive to OGD than cortical neurons. This finding supports
      our in vivo studies showing that mouse hippocampus is more vulnerable than cortex
      after neonatal HI. An imbalance between excess prooxidant production (increased
      nNOS expression, and NO and ROS production) and insufficient antioxidant defenses
      created by reduced GPx activity and GSH levels may, in part, explain the higher
      susceptibility to OGD of immature hippocampal neurons.

PMID- 15473996
TI  - BSE and vCJD cause disturbance to uric acid levels.
AB  - Bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease
      (vCJD) are two new members of the family of neurodegenerative conditions termed
      prion diseases. Oxidative damage has been shown to occur in prion diseases and is
      potentially responsible for the rapid neurodegeneration that is central to the
      pathogenesis of these diseases. An important nonenzymatic antioxidant in the
      brain is uric acid. Analysis of uric acid in the brain and cerebrospinal fluid
      (CSF) of cases of BSE and CJD showed a specific reduction in CSF levels for both
      BSE and variant CJD, but not sporadic CJD. Further studies based on cell culture
      experiments suggested that uric acid in the brain was produced by microglia. Uric
      acid was also shown to inhibit neurotoxicity of a prion protein peptide,
      production of the abnormal prion protein isoform (PrP(Sc)) by infected cells, and
      polymerization of recombinant prion protein. These findings suggest that changes
      in uric acid may aid differential diagnosis of vCJD. Uric acid could be used to
      inhibit cell death or PrP(Sc) formation in prion disease.

PMID- 15473997
TI  - Time-dependent reduction in Abeta levels after intracranial LPS administration in
      APP transgenic mice.
AB  - Inflammation has been argued to play a primary role in the pathogenesis of
      Alzheimer's disease (AD). Lipopolysaccharide (LPS) activates the innate immune
      system, triggering gliosis and inflammation when injected in the central nervous
      system. In studies described here, APP transgenic mice were injected
      intrahippocampally with 4 or 10 microg of LPS and evaluated 1, 3, 7, 14, or 28
      days later. Abeta load was significantly reduced at 3, 7, and 14 days but
      surprisingly returned near baseline 28 days after the injection. No effects of
      LPS on congophilic amyloid deposits could be detected. LPS also activated both
      microglia and astrocytes in a time-dependent manner. The GFAP astrocyte reaction
      and the Fcgamma receptor microglial reaction peaked at 7 days after LPS
      injection, returning to baseline by 2 weeks postinjection. When stained for CD45,
      microglial activation was detected at all time points, although the morphology of
      these cells transitioned from an ameboid to a ramified and bushy appearance
      between 7 and 14 days postinjection. These results indicate that activation of
      brain glia can rapidly and transiently clear diffuse Abeta deposits but has no
      effect on compacted fibrillar amyloid.

PMID- 15473998
TI  - Increased caspase activation in peripheral blood mononuclear cells of patients
      with Alzheimer's disease.
AB  - In this study, we investigated whether alterations in the pattern of caspase
      activation could be found at the level of peripheral blood mononuclear cells
      (PBMCs) in patients with Alzheimer's disease (AD). The results showed that in
      experimental conditions resembling a physiological stimulation, there was a
      statistically significant increase in the enzymatic activity of caspase-3,
      caspase-8, and caspase-9 in PBMCs from a small, but well-characterized, cohort of
      sporadic AD patients compared to those from a comparable control group of aged
      adults (AA). This was accompanied by a parallel, early increase in the cleavage
      activity of the same caspases. The higher level of caspase activity in PBMCs from
      AD compared to AA was not associated with quantitative differences in cell subset
      profiles. Moreover, no increase in apoptosis level, in the same experimental
      conditions, was found in PBMCs from this cohort of AD patients compared to those
      from AA. Conversely, the higher proneness to caspase activation in PBMCs from AD
      patients in comparison with that from AA was associated with a higher
      proliferative response to PHA or CD3. These data show a new dysfunction in AD
      patients at the PBMCs level and suggest that increased proneness to caspase
      activation in lymphocytes could reflect an ongoing systemic response in
      neurodegenerative disease with pathogenetic implications.

PMID- 15473999
TI  - The evolution of A-, F-, and V-type ATP synthases and ATPases: reversals in
      function and changes in the H+/ATP coupling ratio.
AB  - Members of the FoF1, AoA1 and VoV1 family of ATP synthases and ATPases have
      undergone at least two reversals in primary function. The first was from a
      progenitor proton-pumping ATPase to a proton-driven ATP synthase. The second
      involved transforming the synthase back into a proton-pumping ATPase. As proposed
      earlier [FEBS Lett. 259 (1990) 227], these reversals required changes in the
      H+/ATP coupling ratio from an optimal value of about 2 for an ATPase function to
      about 4 for an ATP synthase function. The doubling of the ratio that occurred at
      the ATPase-to-Synthase transition was accomplished by duplicating the gene that
      encodes the nucleotide-binding catalytic subunits followed by loss of function in
      one of the genes. The halving of the ratio that occurred at the Synthase-to
      ATPase transition was achieved by a duplication/fusion of the gene that encodes
      the proton-binding transporter subunits, followed by a loss of function in one
      half of the double-sized protein. These events allowed conservation of quaternary
      structure, while maintaining a sufficient driving force to sustain an adequate
      phosphorylation potential or electrochemical gradient. Here, we describe
      intermediate evolutionary steps and a fine-tuning of the H+/ATP coupling ratio to
      optimize synthase function in response to different environments. In addition, we
      propose a third reversal of function, from an ATPase back to an ATP synthase. In
      contrast to the first two reversals which required a partial loss in function,
      the change in coupling ratio required for the third reversal is explained by a
      gain in function.

PMID- 15474000
TI  - The Arabidopsis thaliana MEK AtMKK6 activates the MAP kinase AtMPK13.
AB  - Mitogen-activated protein (MAP) kinases mediate cellular responses to a wide
      variety of stimuli. Activation of a MAP kinase occurs after phosphorylation by an
      upstream dual-specificity protein kinase, known as a MAP kinase kinase or MEK.
      The Arabidopsis thaliana genome encodes 10 MEKs but few of these have been shown
      directly to activate any of the 20 Arabidopsis MAP kinases. We show here that
      functional complementation of the cell lysis phenotype of a mutant yeast strain
      depends on the co-expression of the Arabidopsis MEK AtMKK6 and the MAP kinase
      AtMPK13. The kinase activity of AtMPK13 is stimulated in the presence of AtMKK6
      in yeast cells. RT-PCR analysis showed the co-expression of these two genes in
      diverse plant tissues. These data show that AtMKK6 can functionally activate the
      MAP kinase AtMPK13.

PMID- 15474001
TI  - Type II phosphoinositide 5-phosphatases have unique sensitivities towards fatty
      acid composition and head group phosphorylation.
AB  - The catalytic properties of the type II phosphoinositide 5-phosphatases of Lowe's
      oculocerebrorenal syndrome, INPP5B, Synaptojanin1, Synaptojanin2 and SKIP were
      analysed with respect to their substrate specificity and enzymological
      properties. Our data reveal that all phosphatases have unique substrate
      specificities as judged by their corresponding KM and VMax values. They also
      possessed an exclusive sensitivity towards fatty acid composition, head group
      phosphorylation and micellar presentation. Thus, the biological function of these
      enzymes will not just be determined by their corresponding regulatory domains,
      but will be distinctly influenced by their catalytic properties as well. This
      suggests that the phosphatase domains fulfil a unique catalytic function that
      cannot be fully compensated by other phosphatases.

PMID- 15474002
TI  - Hypoxia induces transcription of 6-phosphofructo-2-kinase/fructose-2,6
      biphosphatase-4 gene via hypoxia-inducible factor-1alpha activation.
AB  - The PFKFB4 gene encodes isoenzyme of 6-phosphofructo-2-kinase/fructose-2,6
      biphosphatase (PFKFB or PFK-2/FBPase-2) which originally was found in the testes.
      We have studied hypoxic regulation of PFKFB4 gene in prostate cancer cell line,
      PC-3, and several other cancer cell lines. It was shown that hypoxia
      significantly induced PFKFB4 mRNA levels in PC-3 as well as in HeLa, Hep3B and
      HepG2 cell lines. Hypoxia increased PFKFB4 protein levels also. Moreover,
      desferrioxamine and cobalt chloride, which are known to mimic hypoxia, also had a
      stimulatory effect on the expression of PFKFB4 mRNA. In order to investigate the
      mechanisms of hypoxic regulation of PFKFB4 gene expression, we used
      dimethyloxalylglycine, which has the ability to mimic effect of hypoxia by
      significant induction of hypoxia-inducible factor (HIF-1alpha) protein levels.
      Our studies showed that PFKFB4 mRNA expression in PC-3, HeLa, Hep3B and HepG2
      cell lines was highly responsive to dimethyloxalylglycine, an inhibitor of HIF
      1alpha hydroxylase enzymes, suggesting that the hypoxia responsiveness of this
      gene is regulated by HIF proteins. To better understand the hypoxic regulation of
      PFKFB4 gene expression, we isolated genomic DNA, which includes the promoter
      region of PFKFB4. Cell transfection, deletion and site-specific mutagenesis of
      the PFKFB4 promoter region indicates that hypoxic induction of PFKFB4 gene
      expression is mediated by the hypoxia-responsive element (HRE). These experiments
      identified a HRE 422-429 bp upstream from the translation start site. Thus, our
      results indicate that testis-specific form of PFKFB or PFK-2/FBPase-2 is also
      expressed in several cancer cell lines and that hypoxia induces transcription of
      PFKFB4 gene in these cell lines by HIF-1alpha dependent mechanism. HRE in 5'
      promoter region of PFKFB4 gene mediates hypoxic induction of PFKFB4 gene
      transcription.

PMID- 15474003
TI  - Glycosylation of asparagines 136 and 184 is necessary for the alpha2delta subunit
      mediated regulation of voltage-gated Ca2+ channels.
AB  - The CaValpha2delta auxiliary subunit is a glycosylated protein that regulates the
      trafficking and function of voltage-gated Ca2+ channels. One of the most
      prominent roles of CaValpha2delta is to increase whole-cell Ca2+ current
      amplitude. Using N-glycosidase F and truncated forms of CaValpha2delta, earlier
      studies suggested an important role for N-linked glycosylation in current
      stimulation. Here, we used site-directed mutagenesis and heterologous expression
      in HEK-293 cells to examine the impact of individual glycosylation sites within
      the CaValpha2delta subunit on the regulation of Ba2+ currents through recombinant
      Ca2+ channels. We found two N-glycosylation consensus sites (NX(S/T)) in the
      extracellular alpha2 domain of the protein that are functional. Substitution of
      asparagines for glutamines at amino acid positions 136 and 184 rendered these
      sites non-functional as shown by patch-clamp experiments. These results
      corroborate that N-glycosylation is required for the CaValpha2delta subunit
      induced current stimulation and suggest that sites N136 and N184 are directly
      involved in this action. Likewise, N136Q and N184Q mutations prevented whole-cell
      current stimulation without altering its kinetic properties, suggesting a
      regulation on the number of functional channels at the plasma membrane.

PMID- 15474004
TI  - Ratjadone and leptomycin B block CRM1-dependent nuclear export by identical
      mechanisms.
AB  - Research on the export of proteins and nucleic acids from the nucleus to the
      cytoplasm has greatly gained from the discovery that the actinobacterial toxin
      leptomycin B (LMB) specifically inactivates the export receptor chromosomal
      region maintenance 1 (CRM1). Recently, it was shown that myxobacterial
      cytotoxins, named ratjadones (RATs), also bind to CRM1 and inhibit nuclear
      export. However, the reaction mechanism of RATs was not resolved. Here, we show
      that LMB and RAT A employ the same molecular mechanism to inactivate CRM1.
      Alkylation of residue Cys528 of CRM1 determines both LMB and RAT sensitivity and
      prevents nuclear export of CRM1 cargo proteins.

PMID- 15474005
TI  - The plasma membrane Ca2+ pump from proximal kidney tubules is exclusively
      localized and active in caveolae.
AB  - Plasma membrane Ca2+-ATPase is involved in the fine-tuned regulation of
      intracellular Ca2+. In this study, the presence of Ca2+-ATPase in caveolae from
      kidney basolateral membranes was investigated. With the use of a discontinuous
      sucrose gradient, we show that Ca2+-ATPase is exclusively located and fully
      active in caveolin-containing microdomains. Treatment with methyl-beta
      cyclodextrin--a cholesterol chelator--leads to a spreading of both caveolin and
      completely inactive Ca2+-ATPase toward high-density fractions. These data support
      the view that Ca2+ fluxes mediated by Ca2+-ATPase in kidney epithelial cells
      occur only in caveolae, being strictly dependent on the integrity of these
      microdomains.

PMID- 15474006
TI  - The erythrocyte skeletons of beta-adducin deficient mice have altered levels of
      tropomyosin, tropomodulin and EcapZ.
AB  - The erythrocyte membrane cytoskeleton is organized as a polygonal spectrin
      network linked to short actin filaments that are capped by adducin at the barbed
      ends. We have constructed a mouse strain deficient in beta-adducin having
      abnormal erythrocytes. We show here that the levels of several skeletal proteins
      from beta-adducin mutant erythrocytes are altered. In fact, CapZ, the main muscle
      actin-capping protein of the barbed ends that in the erythrocytes is cytoplasmic,
      is 9-fold upregulated in mutant skeletons of erythrocytes suggesting a
      compensatory mechanism. We also detected upregulation of tropomodulin and
      downregulation of alpha-tropomyosin and actin. In addition, purified adducin can
      be re-incorporated into adducin-deficient ghosts.

PMID- 15474007
TI  - Ca2+-dependent interaction of BAPTA with phospholipids.
AB  - Starting from a comparative study of different Ca2+ chelators on the G-protein
      induced inhibition of the CaV2.1 Ca channels, we demonstrate that BAPTA and DM
      nitrophen are able to interact, in a Ca2+- and lipid-dependent manner, with
      phospholipid monolayers. Critical insertion pressure and sensitivity to charged
      lipids indicated that insertion in the lipid film may occur in biological
      membranes as those found on Xenopus oocytes. This novel property is not found for
      EGTA and EDTA and may participate to the unusual ability of BAPTA-related
      molecules to chelate Ca2+ ions in the very close vicinity of the plasma membrane,
      where most of the Ca2+-dependent signalling triggered by voltage-gated Ca2+
      currents occurs.

PMID- 15474008
TI  - Synergetic inhibition of metal ions and genistein on alpha-glucosidase.
AB  - Inhibition of metal ions and synergetic inhibition of metal ions/genistein on
      alpha-glucosidase activity has been investigated. We have examined the inhibitory
      effect of Cu2+, Ni2+, Mg2+, Fe2+, Hg2+, Zn2+, Ca2+, Pb2+, Ag+, V5+, V4+ and Mn2+
      ions. The results show that the nature of the inhibition was reversible, slow
      binding, non-competitive, and the Ki values of some ions such as Cu2+, Ni2+ and
      Zn2+ range from 10(-5) to 10(-6) M. Moreover, synergetic inhibitory effect of
      metal ions and genistein on alpha-glucosidase were studied with kinetics method.
      It is concluded that the inhibitory effect was much greater when both of them
      were added to the reactant solution simultaneously than that they were added,
      respectively, which suggests that the inhibitors seem to bind to the different
      sites of alpha-glucosidase at the same time. Furthermore, the mechanism of the
      synergetic inhibition was examined by spectrophotometry.

PMID- 15474009
TI  - N-glycosylation at Asn(491) in the Asn-Xaa-Cys motif of human transferrin.
AB  - Glycopeptides derived from human transferrin were exhaustively analyzed by matrix
      assisted laser desorption ionization and electrospray ionization mass
      spectrometry (MS). Both MS techniques clearly revealed the sequences of and the
      attachment sites of bi-antennary complex-type oligosaccharides, at both Asn432
      and Asn630, both of which are located in a well-known motif for N-glycosylation,
      Asn-Xaa-Ser/Thr, but also at Asn491 in the Asn-Xaa-Cys motif. The latter has been
      reported to be a minor N-glycosylation site in several glycoproteins. The
      relative abundance of this abnormal glycosylation was estimated to be
      approximately 2 mol% of the transferrin preparation used in this study.

PMID- 15474010
TI  - Transglutaminase catalyzes differential crosslinking of small heat shock proteins
      and amyloid-beta.
AB  - Crosslinking of proteins by tissue transglutaminase (tTG) is enhanced in amyloid
      (Abeta) deposits characteristic of Alzheimer's disease and sporadic inclusion
      body myositis. Small heat shock proteins (sHsps) also occur in amyloid deposits.
      We here report the substrate characteristics for tTG of six sHsps. Hsp27, Hsp20
      and HspB8 are both lysine- and glutamine-donors, alphaB-crystallin only is a
      lysine-donor, HspB2 a glutamine-donor, and HspB3 no substrate at all. Close
      interaction of proteins stimulates crosslinking efficiency as crosslinking
      between different sHsps only takes place within the same heteromeric complex. We
      also observed that alphaB-crystallin, Hsp27 and Hsp20 associate with Abeta in
      vitro, and can be readily crosslinked by tTG.

PMID- 15474011
TI  - Identification of an essential sequence for dihydroceramide C-4 hydroxylase
      activity of mouse DES2.
AB  - Although the amino acid sequences of mouse DES1 (MDES1) and DES2 (MDES2) have 63%
      sequence identity, their enzymatic characteristics are quite different. MDES1
      exhibits high dihydroceramide delta4-desaturase activity and very low C-4
      hydroxylase activity, while MDES2 is similarly active as both a dihydroceramide
      delta4-desaturase and a C-4 hydroxylase. We constructed several chimeras of MDES1
      and MDES2 and identified a region important for C-4 hydroxylase activity in
      MDES2. This region contains the sequence XAFGY (X=T or A or V; Y=T or N) and
      occurs on the C-terminal side of the first His-box of MDES2. We confirmed the
      conservation of this region in DES2 family members sequenced from humans, pigs,
      rats, chickens, zebrafish, and Xenopus.

PMID- 15474012
TI  - Elsamicin A binding to DNA. A comparative thermodynamic characterization.
AB  - The antitumor drug elsamicin A contains a coumarin-related chartarin chromophore
      that intercalates into DNA. It differs from other related molecules in its
      disaccharide moiety, which bears an amino sugar. Its binding to DNA was analyzed
      using isothermal titration calorimetry and UV thermal denaturation, and
      characterized thermodynamically. For the association of elsamicin A with DNA we
      found DeltaG degrees = -8.6 kcal mol(-1), DeltaH = -10.4 kcal mol(-1), DeltaS = 
      6.1 cal mol(-1) K(-1), and Kobs = 2.8(+/- 0.2) x 10(6) M(-1) at 20 degrees C in
      18 mM Na+. The contributions to the free energy of binding that lead to the DNA
      elsamicin complex are compared with the binding to DNA of chartreusin, another
      chartarin-containing drug. The results are discussed in terms of the
      contributions of the disaccharide moieties into the strength of binding.

PMID- 15474013
TI  - Cyclopiazonic acid reduces the coupling factor of the Ca2+-ATPase acting on Ca2+
      binding.
AB  - The mycotoxin cyclopiazonic acid (CPA) is a potent inhibitor of the sarcoplasmic
      reticulum Ca2+-ATPase. The compound decreases the affinity of the Ca2+-ATPase for
      Ca2+ and reduces the maximum specific activity of the enzyme. Furthermore, CPA
      abolishes the cooperativity of Ca2+ transport, showing a Ca2+/ATP ratio
      approximately 1 at any extent of Ca2+ saturation. There is also an effect on the
      Ca2+-binding mechanism, where the addition of CPA results in binding of only half
      maximal amount of Ca2+ observed in its absence. The experimental data suggest
      that in the presence of CPA, only a single Ca2+ ion binds to the Ca2+-ATPase.

PMID- 15474014
TI  - Distance dependence of interactions between charged centres in proteins with
      common structural features.
AB  - Data collected for interactions among redox centres, and interactions between
      redox centres and acid-base residues in a family of small multihaem cytochromes
      are analysed. The distance dependent attenuation of the interactions between non
      surface charges, for separations that range from 8 to 23 angstroms, can be
      described by a simple function derived from the Debye-Huckel formalism, fit to
      9.5 and 7.6 as values for the relative dielectric constant and Debye length,
      respectively. However, there is considerable scatter in the data despite the
      structural similarities among the proteins, which is discussed in the framework
      of using such simple models in predicting properties of novel proteins.

PMID- 15474015
TI  - Overproduction of CcmABCDEFGH restores cytochrome c maturation in a DsbD deletion
      strain of E. coli: another route for reductant?
AB  - The multidomain transmembrane protein DsbD is essential for cytochrome c
      maturation (Ccm) in Escherichia coli and transports reductant to the otherwise
      oxidising environment of the bacterial periplasm. The Ccm proteins ABCDEFGH are
      also essential and we show that the overproduction of these proteins can
      unexpectedly complement for the absence of DsbD in a deletion strain by partially
      restoring the production of an exogenous c-type cytochrome under aerobic and
      anaerobic conditions. This suggests that one or more of the Ccm proteins can
      provide reductant to the periplasm. The Ccm proteins do not, however, restore the
      normal disulfide mis-isomerisation phenotype of the deletion strain, as shown by
      assay of the multidisulfide-bonded enzyme urokinase.

PMID- 15474016
TI  - A20 is a potent inhibitor of TLR3- and Sendai virus-induced activation of NF
      kappaB and ISRE and IFN-beta promoter.
AB  - Toll-like receptor 3 (TLR3) recognizes dsRNA generated during viral infection and
      activation of TLR3 results in induction of type I interferons (IFNs) and cellular
      anti-viral response. TLR3 is associated with a TIR domain-containing adapter
      protein TRIF, which activates distinct downstream pathways leading to activation
      of NF-kappaB and ISRE sites in the promoters of type I IFNs. We show here that
      A20, a NF-kappaB-inducible zinc finger protein that has been demonstrated to be
      an inhibitor of TNF-induced NF-kappaB activation and a physiological suppressor
      of inflammatory response, potently inhibited TLR3- and Sendai virus-mediated
      activation of ISRE and NF-kappaB and IFN-beta promoter in reporter gene assays.
      A20 also inhibited TRIF-, but not its downstream signaling components TBK1-,
      IKKbeta-, and IKKepsilon-mediated activation of ISRE and NF-kappaB and IFN-beta
      promoter. Moreover, A20 interacted with TRIF in co-immunoprecipitation
      experiments. Finally, expression of A20 could be induced at protein level by
      Sendai virus infection. These data suggest that A20 targets TRIF to inhibit TLR3
      mediated induction of IFN-beta transcription and functions as a feedback negative
      regulator for TLR3 signaling and cellular anti-viral response.

PMID- 15474017
TI  - Solution structure of coactosin reveals structural homology to ADF/cofilin family
      proteins.
AB  - Coactosin is a small (MW approximately 15 kDa) evolutionarily conserved actin
      filament binding protein. It displays remote sequence homology to ADF/cofilin
      proteins and to the ADF-H domains of twinfilin and Abp1/drebrin. However,
      biochemical analyses have demonstrated that coactosin has a very different role
      in actin dynamics from the ones of ADF/cofilin, twinfilin or Abp1/drebrin. To
      elucidate the molecular mechanism of coactosin/actin interaction, we determined
      the three-dimensional structure of mouse coactosin by multidimensional NMR
      spectroscopy. We find that the coactosin structure is homologous to ADF/cofilin
      and to the ADF-H domains of twinfilin. Furthermore, the regions that have been
      shown to be important for actin filament interactions in ADF/cofilins are
      structurally conserved in coactosin suggesting that these two proteins interact
      with F-actin through a conserved interface. Our analysis also identifies key
      structural differences between these proteins that may account for the
      differences in biochemical activities and cellular roles of these proteins.

PMID- 15474018
TI  - F(1)F(0) ATP synthase subunit c is targeted by the SRP to YidC in the E. coli
      inner membrane.
AB  - Escherichia coli inner membrane proteins (IMPs) use different pathways for
      targeting and membrane integration. We have examined the biogenesis of the F1F0
      ATP synthase subunit c, a small double spanning IMP, using complementary in vivo
      and in vitro approaches. The data suggest that F0c is targeted by the SRP to the
      membrane, where it inserts at YidC in a Sec-independent mechanism. F0c appears to
      be the first natural substrate of this novel pathway.

PMID- 15474019
TI  - Kinetics of interprotein electron transfer between cytochrome c6 and the soluble
      CuA domain of cyanobacterial cytochrome c oxidase.
AB  - Cytochrome c6 is a soluble metalloprotein located in the periplasmic space and
      the thylakoid lumen of many cyanobacteria and is known to carry electrons from
      cytochrome b6f to photosystem I. The CuA domain of cytochrome c oxidase, the
      terminal enzyme which catalyzes the four-electron reduction of molecular oxygen
      in the respiratory chains of mitochondria and many bacteria, also has a
      periplasmic location. In order to test whether cytochrome c6 could also function
      as a donor for cytochrome c oxidase, we investigated the kinetics of the electron
      transfer between recombinant cytochrome c6 (produced in high yield in Escherichia
      coli by coexpressing the maturation proteins encoded by the ccmA-H gene cluster)
      and the recombinant soluble CuA domain (i.e., the donor binding and electron
      entry site) of subunit II of cytochrome c oxidase from Synechocystis PCC 6803.
      The forward and the reverse electron transfer reactions were studied by the
      stopped-flow technique and yielded apparent bimolecular rate constants of (3.3 +/
      0.3) x 10(5) M(-1) s(-1) and (3.9 +/- 0.1) x 10(6) M(-1) s(-1), respectively, in
      5 mM potassium phosphate buffer, pH 7, containing 20 mM potassium chloride and 25
      degrees C. This corresponds to an equilibrium constant Keq of 0.085 in the
      physiological direction (DeltarG'0 = 6.1 kJ/mol). The reduction of the CuA
      fragment by cytochrome c6 is almost independent on ionic strength, which is in
      contrast to the reaction of the CuA domain with horse heart cytochrome c, which
      decreases with increasing ionic strength. The findings are discussed with respect
      to the potential role of cytochrome c6 as mobile electron carrier in both
      cyanobacterial electron transport pathways.

PMID- 15474020
TI  - Protein A--a new ligand for human C-reactive protein.
AB  - Phosphorylcholine (PC) is a classical ligand of C-reactive protein (CRP), a
      clinically important acute phase protein. In search of new ligands, CRPs were
      affinity-purified from several pathological samples, which exhibited distinct
      molecular variants induced in different diseases. Both glycosylated and non
      glycosylated CRPs showed calcium-independent differential-binding to
      Staphylococcus aureus cell-surface Protein A. CRP possesses separate binding
      sites for Protein A and PC with different binding constants. We have demonstrated
      that Protein A is another ligand in addition to PC establishing an extended
      definition of CRP. Protein A binding may impart immunomodulatory roles of CRP in
      combating microorganisms or other foreign materials.

PMID- 15474021
TI  - Clustering of cellular prion protein induces ERK1/2 and stathmin phosphorylation
      in GT1-7 neuronal cells.
AB  - The physiological role of the prion protein is largely unknown. Here, clustering
      of prion at the surface of GT1-7 cells was observed upon anti-prion antibody
      treatments. This clustering was associated with a rapid and transient
      phosphorylation of the mitogen activated protein kinases (MAPKs) extracellular
      receptor kinases 1 and 2 (ERK1/2), and also of the microtubule-destabilizing
      protein stathmin at serine 16. The specificity of this antibody-mediated
      activation was ascertained by its inhibition by prion small interfering RNA. The
      phosphorylation of ERK1/2 but not that of stathmin was abolished by the MAPK/ERK
      kinase 1 inhibitor U0126, whereas both signaling pathways were blocked by the
      specific inhibitor of the epidermal growth factor receptor AG1478, suggesting the
      likely recruitment of this receptor upon prion clustering.

PMID- 15474022
TI  - Autoregulation of regulatory proteins is key for dynamic operation of GAL switch
      in Saccharomyces cerevisiae.
AB  - Autoregulation and nucleocytoplasmic shuttling play important roles in the
      operation of the GAL regulatory system. However, the significance of these
      mechanisms in the overall operation of the switch is unclear. In this work, we
      develop a dynamic model for the GAL system and further validate the same using
      steady-state and dynamic experimental expression data. Next, the model is used to
      delineate the relevance of shuttling and autoregulation in response to inducing,
      repressing, and non-inducing-non-repressing media. The analysis indicates that
      autoregulation of the repressor, Gal80p, is key in obtaining three distinct
      steady states in response to the three media. In particular, the analysis
      rationalizes the intuitively paradoxical observation that the concentration of
      repressor, Gal80p, actually increases in response to an increase in the inducer
      concentration. On the other hand, although nucleocytoplasmic shuttling does not
      affect the dynamics of the system, it plays a dominant role in obtaining a
      sensitive response to galactose. The dynamic model was also used to obtain
      insights on the preculturing effect on the system behavior.

PMID- 15474023
TI  - Syndecan-dependent binding of Drosophila hemocytes to laminin alpha3/5 chain LG4
      5 modules: potential role in sessile hemocyte islets formation.
AB  - Heparin-column chromatography and elastase-digestion of medium from hemocyte
      Kc167 gave Drosophila laminin alpha3/5betagamma trimer, alpha3/5LG2-3 and
      alpha3/5LG4-5 modules with eluting NaCl concentrations of 450, 280 and 450 mM,
      respectively. Kc167 cells bound dish surface with alpha3/5betagamma trimer or
      alpha3/5LG4-5, but not with alpha3/5LG2-3 modules. Cell binding was counteracted
      by treating with heparin or heparan sulfate. RNA interference of syndecan in
      Kc167 cells impaired the binding, but that of dally or dally-like did not. Green
      fluorescent protein-expressing hemocytes also bound surface with
      alpha3/5betagamma trimer or alpha3/5LG4-5 module. Thus, syndecan-dependent
      binding of hemocytes to laminin may have a potential role in sessile hemocytes
      islets formation in T2-A8 segments of Drosophila.

PMID- 15474024
TI  - Gluconate dehydratase from the promiscuous Entner-Doudoroff pathway in Sulfolobus
      solfataricus.
AB  - An investigation has been carried out into gluconate dehydratase from the
      hyperthermophilic Archaeon Sulfolobus solfataricus. The enzyme has been purified
      from cell extracts of the organism and found to be responsible for both gluconate
      and galactonate dehydratase activities. It was shown to be a 45 kDa monomer with
      a half-life of 41 min at 95 degrees C and it exhibited similar catalytic
      efficiency with both substrates. Taken alongside the recent work on glucose
      dehydrogenase and 2-keto-3-deoxygluconate aldolase, this report clearly
      demonstrates that the entire non-phosphorylative Entner-Doudoroff pathway of S.
      solfataricus is promiscuous for the metabolism of both glucose and galactose.

PMID- 15474025
TI  - Indole-3-carbinol activates the cyclin-dependent kinase inhibitor p15(INK4b)
      gene.
AB  - Indole-3-carbinol (I3C) is a naturally occurring compound found in vegetables
      such as broccoli and cauliflower, and has been shown to arrest human tumor cells
      in the G1 phase of the cell cycle. However, the molecular mechanism responsible
      for this effect has not been sufficiently elucidated. We report here that I3C
      activates the cyclin-dependent kinase (CDK) inhibitor p15INK4b gene through its
      promoter, accompanied by cell growth inhibition in HaCaT cells. Treatment with
      I3C almost did not affect the expressions of the other CDK inhibitors such as
      p19INK4d, p21WAF1 and p27Kip1. These results suggest that p15INK4b is an
      important molecular target of I3C among CDK inhibitors.

PMID- 15474026
TI  - Functional and molecular characterization of the frataxin homolog from
      Arabidopsis thaliana.
AB  - Frataxin is a highly conserved protein from bacteria to mammals that has been
      proposed to participate in iron-sulfur cluster assembly and mitochondrial iron
      homeostasis. In higher organisms, the frataxin gene is nuclear-encoded and the
      protein is required for maintenance of normal mitochondrial iron levels and
      respiration. We describe here AtFH, a plant gene with significant homology to
      other members of the frataxin family. Plant frataxin has five segments of beta
      regions and two alpha helices, which are characteristics of human frataxin, as
      well as a potential N-terminal targeting peptide for the mitochondrial
      localization. Transcription analysis showed that AtFH is ubiquitously expressed
      with high levels in flowers. Complementation of a Saccharomyces cerevisiae mutant
      (Deltayfh) lacking the frataxin gene proved that AtFH is a functional protein,
      because it restored normal rates of respiration, growth and sensitivity to H2O2
      of the null mutant. Our results support the involvement of AtFH in mitochondrial
      respiration and survival during oxidative stress in plants. This is the first
      report of a functional frataxin gene in plants.

PMID- 15474028
TI  - Mitochondrial electron transport as a source for nitric oxide in the unicellular
      green alga Chlorella sorokiniana.
AB  - Wild type (WT), and nitrate reductase (NR)- and nitrite-reductase (NiR)-deficient
      cells of Chlorella sorokiniana were used to characterize nitric oxide (NO)
      emission. The NO emission from nitrate-grown WT cells was very low in air,
      increased slightly after addition of nitrite (200 microM), but strongly under
      anoxia. Importantly, even completely NR-free mutants, as well as cells grown on
      tungstate, emitted NO when fed with nitrite under anoxia. Therefore, this NO
      production from nitrite was independent of NR and other molybdenum cofactor
      enzymes. Cyanide and inhibitors of mitochondrial complex III, myxothiazol or
      antimycin A, but not salicylhydroxamic acid (inhibitor of alternative oxidase)
      inhibited NO production by NR-free cells. In contrast, NiR-deficient cells
      growing on nitrate accumulated nitrite and emitted NO at very high equal rates in
      air and anoxia. This NO emission was 50% inhibited by salicylhydroxamic acid,
      indicating that in these cells the alternative oxidase pathway had been induced
      and reduced nitrite to NO.

PMID- 15474027
TI  - Determination and comparison of specific activity of the HIF-prolyl hydroxylases.
AB  - Hypoxia-inducible factor (HIF) is a transcriptional complex that is regulated by
      oxygen sensitive hydroxylation of its alpha subunits by the prolyl hydroxylases
      PHD1, 2 and 3. To better understand the role of these enzymes in directing
      cellular responses to hypoxia, we derived an assay to determine their specific
      activity in both native cell extracts and recombinant sources of enzyme. We show
      that all three are capable of high rates of catalysis, in the order
      PHD2=PHD3>PHD1, using substrate peptides derived from the C-terminal degradation
      domain of HIF-alpha subunits, and that each demonstrates similar and remarkable
      sensitivity to oxygen, commensurate with a common role in signaling hypoxia.

PMID- 15474029
TI  - Endothelin-1 is an essential co-factor for beta2-adrenergic receptor-induced
      proliferation of human cardiac fibroblasts.
AB  - We previously demonstrated that chronic stimulation of the beta2-adrenergic
      receptor (beta2-AR) increases proliferation of cultured human cardiac fibroblasts
      (CF) via an autocrine mechanism. Here, we investigated the role of endothelin-1
      (ET-1) in this process. ETA-receptor antagonism or protein kinase C inhibition
      abolished the beta2-AR-induced increase in cell proliferation. RT-PCR and ELISA
      analysis demonstrated that although CF synthesized and secreted ET-1, this
      occurred independently of beta2-AR stimulation. Furthermore, despite activation
      of the MAP kinase pathway, ET-1 treatment did not stimulate CF proliferation.
      Therefore, the role of ET-1 in this process is that of an essential co-factor
      acting independently of beta2-AR stimulation.

PMID- 15474030
TI  - Mouse acetylcholinesterase interacts in yeast with the extracellular matrix
      component laminin-1beta.
AB  - Acetylcholinesterase (AChE) is likely to have roles other than the hydrolysis of
      acetylcholine, e.g., related to developmental processes like neurite outgrowth,
      differentiation and adhesion. Here, we investigated whether AChE can function as
      a heterophilic cell adhesion molecule and searched for proteins interacting with
      it. Using the yeast two-hybrid method and a mouse brain cDNA library, we have
      identified an interaction between a partial cDNA encoding the globular domain IV
      of laminin chain beta1 and the amino acids 240-503 of mouse AChE. Biochemical co
      immunoprecipitation assays confirmed the genetic results. We suggest that AChE,
      by interacting with laminin-1, is able to exert changes in adhesion signaling
      pathways.

PMID- 15474031
TI  - Interactions of 12-lipoxygenase with phospholipase A2 isoforms following platelet
      activation through the glycoprotein VI collagen receptor.
AB  - Recent studies implicate the collagen receptor, glycoprotein VI (GPVI) in
      activation of platelet 12-lipoxygenase (p12-LOX). Herein, we show that GPVI
      stimulated 12-hydro(peroxy)eicosatetraenoic acid (H(P)ETE) synthesis is inhibited
      by palmityl trifluromethyl ketone or oleyloxyethylphosphocholine , but not
      bromoenol lactone, implicating secretory and cytosolic, but not calcium
      independent phospholipase A2 (PLA2) isoforms. Also, following GPVI activation, 12
      LOX co-immunoprecipitates with both cytosolic and secretory PLA2 (sPLA2).
      Finally, venoms containing sPLA2 acutely activate p12-LOX in a dose-dependent
      manner. This study shows that platelet 12-H(P)ETE generation utilizes
      arachidonate substrate from both c- and sPLA2 and that 12-LOX functionally
      associates with both PLA2 isoforms.

PMID- 15474032
TI  - The role of raffinose in the cold acclimation response of Arabidopsis thaliana.
AB  - In many plants raffinose family oligosaccharides are accumulated during cold
      acclimation. The contribution of raffinose accumulation to freezing tolerance is
      not clear. Here, we investigated whether synthesis of raffinose is an essential
      component for acquiring frost tolerance. We created transgenic lines of
      Arabidopsis thaliana accessions Columbia-0 and Cape Verde Islands constitutively
      overexpressing a galactinol synthase (GS) gene from cucumber. GS overexpressing
      lines contained up to 20 times as much raffinose as the respective wild-type
      under non-acclimated conditions and up to 2.3 times more after 14 days of cold
      acclimation at 4 degrees C. Furthermore, we used a mutant carrying a knockout of
      the endogenous raffinose synthase (RS) gene. Raffinose was completely absent in
      this mutant. However, neither the freezing tolerance of non-acclimated leaves,
      nor their ability to cold acclimate were influenced in the RS mutant or in the GS
      overexpressing lines. We conclude that raffinose is not essential for basic
      freezing tolerance or for cold acclimation of A. thaliana.

PMID- 15474033
TI  - Efficient assembly and release of SARS coronavirus-like particles by a
      heterologous expression system.
AB  - Virus-like particles (VLPs) produced by recombinant expression of the major viral
      structural proteins could be an attractive method for severe acute respiratory
      syndrome (SARS) control. In this study, using the baculovirus system, we
      generated recombinant viruses that expressed S, E, M and N structural proteins of
      SARS-CoV either individually or simultaneously. The expression level, size and
      authenticity of each recombinant SARS-CoV protein were determined. In addition,
      immunofluorescence and FACS analysis confirmed the cell surface expression of the
      S protein. Co-infections of insect cells with two recombinant viruses
      demonstrated that M and E could assemble readily to form smooth surfaced VLPs. On
      the other hand, simultaneous high level expression of S, E and M by a single
      recombinant virus allowed the very efficient assembly and release of VLPs. These
      data demonstrate that the VLPs are morphological mimics of virion particles. The
      high level expression of VLPs with correct S protein conformation by a single
      recombinant baculovirus offers a potential candidate vaccine for SARS.

PMID- 15474034
TI  - Control of 4E-BP1 expression in mouse brown adipose tissue by the beta3
      adrenoceptor.
AB  - Knockout of the translation inhibitor 4E-BP1 induces an overexpression of
      uncoupling protein-1 (UCP1) [Nature Medicine 7 (2001) 1128]. A possible inverse
      control of UCP1 and 4E-BP1 expressions in mouse brown adipose tissue was
      investigated. Cold-exposure, which increases the expression of UCP1, decreased
      that of 4E-BP1 mRNA in wild type but not in beta1/beta2/beta3-adrenoceptor
      knockout mice. Administration of the beta3-adrenoceptor agonist CL 316246
      decreased 4E-BP1 mRNA by 75% and protein by 41% after 6 and 48 h, respectively.
      Our data are the first report of a regulation by the beta3-adrenoceptor of 4E-BP1
      expression. They support a role of the latter in adaptive thermogenesis.

PMID- 15474035
TI  - Expression of tau mRNA and soluble tau isoforms in affected and non-affected
      brain areas in Alzheimer's disease.
AB  - In Alzheimer's disease (AD), selective expression of tau isoforms might underlie
      the susceptibility of different brain areas to develop neurofibrillary tangles
      and this pattern might change in the disease. In this study, we have analyzed in
      control subjects and in sporadic AD patients the pattern of expression of tau
      mRNA and tau proteins in areas unaffected (cerebellar cortex, white matter),
      moderately affected (occipital striate cortex, thalamus, caudate nucleus, and
      putamen) or strongly affected by neurofibrillary tangles (temporal and frontal
      associative cortex). After RT-PCR amplification, five products corresponding to
      the tau mRNAs containing exons 2 and 3, exon 2, without exons 2 or 3, with exon
      10 and without exon 10 were identified. In control subjects, these five PCR
      products were present in all areas except in white matter, where transcripts with
      exons 2 or exons 2 and 3 were not identified. In AD patients, the same pattern of
      transcripts was observed in different areas, regardless of the presence of
      neurofibrillary lesions. After dephosphorylation of soluble tau proteins, the six
      tau isoforms were identified in the same areas by immunoblotting, including in
      the white matter, suggesting that most tau isoforms with exons 2 and 3 are
      transported along axons. The relative expression of 0N3R isoforms was higher in
      the temporal cortex than in the cerebellar cortex, both in control and AD
      subjects. The qualitative pattern of expression was identical in subjects with or
      without an APOE4 allele. Our results suggest that splicing regulation of the tau
      gene and the relative expression of tau isoforms are not significantly changed in
      sporadic cases of the disease, although differential expression of tau isoforms
      in temporal cortex might underlie this brain area susceptibility to
      neurofibrillary tangles formation.

PMID- 15474036
TI  - ERR-10: a new repressor in transcriptional signaling activation of estrogen
      receptor-alpha.
AB  - Estrogen receptor-alpha (ER-alpha) is a nuclear transcriptional factor that is
      part of the nuclear receptor superfamily. In this study, we isolated and
      identified a new LXXLL-containing protein that interacts with the ER-alpha via a
      yeast two-hybrid assay. We have termed this protein estrogen receptor repressor
      10 (ERR-10). The ERR-10 cDNA is predicted to encode a polypeptide of 94 amino
      acids, with a molecular mass of about 10 kDa. Although the ERR-10 mRNA transcript
      is expressed in a wide range of normal human tissues, higher expression levels
      are found in endocrinal tissues relative to other tissues. We have demonstrated,
      through immunoprecipitation, Western blot and GST pull-down assays, that ERR-10
      associates with ER-alpha. Moreover, ERR-10 decreased 17beta-estrodial-induced
      activation of ER-alpha transcriptional activity in transient transfection assays
      of mammalian cells. The ERR-10 N-terminus, which resembles two LXXLL motifs, is
      essential for ER-alpha binding and repression activity. Estrogen modulation of
      estrogen-responsive gene expression was markedly blocked by ERR-10. These results
      suggest that ERR-10 is a novel mediator in ER transcriptional activation.

PMID- 15474037
TI  - Interaction of the bacterial terminal oxidase cytochrome bd with nitric oxide.
AB  - Cytochrome bd is a prokaryotic terminal oxidase catalyzing O2 reduction to H2O.
      The oxygen-reducing site has been proposed to contain two hemes, d and b595, the
      latter presumably replacing functionally CuB of heme-copper oxidases. We show
      that NO, in competition with O2, rapidly and potently (Ki = 100 +/- 34 nM at
      approximately 70 microM O2) inhibits cytochrome bd isolated from Escherichia coli
      and Azotobacter vinelandii in turnover, inhibition being quickly and fully
      reverted upon NO depletion. Under anaerobic reducing conditions, neither of the
      two enzymes reveals NO reductase activity, which is proposed to be associated
      with CuB in heme-copper oxidases.

PMID- 15474038
TI  - Effect of lipids with different spontaneous curvature on the channel activity of
      colicin E1: evidence in favor of a toroidal pore.
AB  - The channel activity of colicin E1 was studied in planar lipid bilayers and
      liposomes. Colicin E1 pore-forming activity was found to depend on the curvature
      of the lipid bilayer, as judged by the effect on channel activity of curvature
      modulating agents. In particular, the colicin-induced trans-membrane current was
      augmented by lysophosphatidylcholine and reduced by oleic acid, agents promoting
      positive and negative membrane curvature, respectively. The data obtained imply
      direct involvement of lipids in the formation of colicin E1-induced pore walls.
      It is inferred that the toroidal pore model previously validated for small
      antimicrobial peptides is applicable to colicin E1, a large protein that contains
      ten alpha-helices in its pore-forming domain.

PMID- 15474039
TI  - Post-transcriptional regulation of the psbA gene family in the cyanobacterium
      Synechococcus sp. PCC 7942.
AB  - In the cyanobacterium Synechococcus sp. PCC 7942, the photosystem II reaction
      center protein D1 is encoded by three psbA genes. The psbAI gene encodes the D1:1
      protein that is the prevailing form under steady state conditions, whereas the
      expression of the psbAII and psbAIII genes, encoding the D1:2 protein, is
      enhanced under many stress conditions. Here, we show that in addition to
      transcriptional control, the synthesis of D1 protein forms is regulated at the
      levels of membrane targeting of psbA mRNA ribosome complexes and translation
      elongation, whereas the formation of translation initiation complexes does not
      have a significant regulatory role.

PMID- 15474040
TI  - Synergistic activation of insect cAMP-dependent protein kinase A (type II) by
      cyclicAMP and cyclicGMP.
AB  - The high cGMP sensitivity of cAMP-dependent protein kinase A (type II) (PKAII)
      from invertebrates led to the hypothesis that cGMP directly activates PKAII under
      physiological conditions. We tested this idea using PKAII holoenzyme purified
      from the honeybee brain in an assay with short stimulation times. In the presence
      of very low cAMP concentrations, we found a synergistic increase in PKAII
      activation by physiological cGMP concentrations. Cloning honeybee regulatory
      subunit RII and phylogenetic comparison of the two cyclic nucleotide-binding
      sites of RII reveal a high relation of domain A of insect RII with cGMP-binding
      domains of cGMP-dependent protein kinases.

PMID- 15474041
TI  - Translin associated protein X is essential for cellular proliferation.
AB  - DNA vectors that express short hairpin RNAs (shRNAs) provide a new tool for
      reverse genetic analysis for selective long-term reduction of gene expression in
      mammalian cells. Using shRNA constructs with a cytomegalovirus promoter and an
      actin intron between the hairpins for stabilization, we reduce expression of an
      exogenously expressed gene, GFP and the endogenous protein, Translin-associated
      factor X (TRAX), in stably transfected Hela cell lines. The reduction of TRAX in
      Hela cells causes reduced cell proliferation. This decrease is specific as there
      is no equivalent reduction of the TRAX interacting protein, Testis brain RNA
      binding protein, or any significant increase in a number of interferon-related
      target genes.

PMID- 15474042
TI  - Production of maltodextrin 1-phosphate by Fibrobacter succinogenes S85.
AB  - We show for the first time the occurrence of maltodextrin-1-Phosphate (MD-1P)
      (DP2) in F. succinogenes S85, a rumen bacterium specialized in cellulolysis which
      is not able to use maltose and starch. MD-1P were found in intra and
      extracellular medium of resting cells incubated with glucose. We used 2D 1H NMR
      technique and TLC to identify their structure and quantify their production with
      time. It was also shown that these phosphorylated oligosaccharides originated
      both from exogenous glucose and endogenous glycogen.

PMID- 15474043
TI  - A modified mammalian tandem affinity purification procedure to prepare functional
      polycystin-2 channel.
AB  - The tandem affinity purification (TAP) procedure was initially developed as a
      tool for rapid purification of native protein complexes expressed at their
      natural levels in yeast cells. This purification procedure was also applied to
      study interactions between soluble proteins in mammalian cells. In order to apply
      this procedure to mammalian membrane proteins, we created a modified TAP tag
      expression vector and fused with the PKD2 gene, encoding a membrane cation
      channel protein, polycystin-2, mutated in 15% of autosomal dominant polycystic
      kidney disease. We generated epithelial Madin-Darby canine kidney cell line
      stably expressing TAP-tagged polycystin-2, improved the subsequent steps for
      membrane protein release and stability, and succeeded in purifying this protein.
      Using patch clamp electrophysiology, we detected specific polycystin-2 channel
      activities when the purified protein was reconstituted into a lipid bilayer
      system. Thus, this modified TAP procedure provides a powerful alternative to
      functionally characterize membrane proteins, such as ion channels, transporters
      and receptors, using cell-free system derived from mammalian cells.

PMID- 15474044
TI  - An episodic ataxia type-1 mutation in the S1 segment sensitises the hKv1.1
      potassium channel to extracellular Zn2+.
AB  - Episodic ataxia type-1 (EA1) is a human neurological syndrome characterized by
      attacks of generalized ataxia and by continuous myokymia that has been associated
      with point mutations in the voltage-gated potassium channel gene KCNA1. Although
      important advancement has been made in understanding the molecular
      pathophysiology of EA1, several disease-causing mechanisms remain poorly
      understood. F184C is an EA1 mutation that is located within the S1 segment of the
      human Kv1.1 subunit. Here, we show that the F184C mutation increases
      approximately 4.5-fold the sensitivity of the channel to extracellular Zn2+. Both
      Zn2+and Cd2+ markedly alter the activation kinetics of F184C channel. In
      addition, the mutated channel reacts with several methane thiosulfonate reagents
      which specifically affected channel function. The results provide structural
      implications and indicate that sensitisation of hKv1.1 to Zn2+ is likely to
      contribute to the EA1 symptoms in patients harboring the F184C mutation.

PMID- 15474046
TI  - Laccase from Melanocarpus albomyces binds effectively to cellulose.
AB  - A laccase from the thermophilic fungus Melanocarpus albomyces was shown to bind
      to softwood and pure microcrystalline cellulose. The binding isotherm fitted well
      the Langmuir type one-site binding model. The adsorption parameters indicated
      that M. albomyces laccase binds with high affinity to cellulose with a relatively
      low maximum binding capacity, as compared to the values for various cellulases.
      The binding was shown to be reversible and not influenced by non-specific protein
      or 0.1-0.5 M Na2SO4. No binding was detected with laccases from Trametes hirsuta
      or Mauginiella sp., which suggests that binding to cellulose is typical for only
      some laccases.

PMID- 15474045
TI  - The C. elegans methionine aminopeptidase 2 analog map-2 is required for germ cell
      proliferation.
AB  - We have investigated the physiological function of type 2 methionine
      aminopeptidases (MetAP2) using Caenorhabditis elegans as a model system. A
      homolog of human MetAP2 was found in the C. elegans genome, which we termed MAP
      2. MAP-2 protein displayed methionine aminopeptidase activity and was sensitive
      to inhibition by fumagillin. Downregulation of map-2 expression by RNAi led to
      sterility, resulting from a defect in germ cell proliferation. These observations
      suggest that MAP-2 is essential for germ cell development in C. elegans and that
      this ubiquitous enzyme may play important roles in a tissue specific manner.

PMID- 15474047
TI  - Beta-synuclein exhibits chaperone activity more efficiently than alpha-synuclein.
AB  - Beta-synuclein exhibits high sequence homology and structural similarity with
      alpha-synuclein, a protein implicated in the pathogenesis of Parkinson's disease.
      We investigated the chaperone function of beta-synuclein and its anti-fibrillar
      activity in comparison with alpha-synuclein. beta-Synuclein suppressed the heat
      induced aggregation of aldolase, alcohol dehydrogenase, and citrate synthase, and
      its anti-aggregative activity was remarkably higher than that of alpha-synuclein.
      Heat-induced inactivation of citrate synthase was significantly protected by beta
      synuclein. Moreover, beta-synuclein inhibited the amyloid formation of both
      Abeta(1-40) and alpha-synuclein. It is, therefore, suggested that beta-synuclein
      can prevent abnormal protein aggregations more effectively than alpha-synuclein
      by acting as a molecular chaperone.

PMID- 15474048
TI  - Cell-type specific modification of PII is involved in the regulation of nitrogen
      metabolism in the cyanobacterium Anabaena PCC 7120.
AB  - In the heterocystous cyanobacterium Anabaena PCC 7120, the modification state of
      the signalling PII protein is regulated according to the nitrogen regime of the
      cells, as already observed in some unicellular cyanobacteria. However, during the
      adaptation to diazotrophic growth conditions, PII is phosphorylated in vegetative
      cells while unphosphorylated in heterocysts. Isolation of mutants affected on PII
      modification state and analysis of their phenotypes allow us to show the
      implication of PII in the regulation of molecular nitrogen assimilation and more
      specifically, the requirement of unmodified state of PII in the formation of
      polar nodules of cyanophycin in heterocysts.

PMID- 15474049
TI  - Heterologously expressed protein phosphatase calcineurin downregulates plant
      plasma membrane H+-ATPase activity at the post-translational level.
AB  - To investigate the effects of calcineurin expression on cellular ion homeostasis
      in plants, we have obtained a transgenic cell culture of tomato, expressing
      constitutively activated yeast calcineurin. Transgenic cells exhibited reduced
      growth rates and proton extrusion activity in vivo. We show that reduction of
      plasma membrane H+-ATPase activity by expression of calcineurin is the basis for
      the observed phenotypes. Transgenic calli and cell suspensions displayed also
      increased salt tolerance and contained slightly higher Ca2+ and K+ levels. This
      demonstrates that calcineurin can modulate ion homeostasis in plants as it does
      in yeast by affecting the activity of primary ion transporters.

PMID- 15474050
TI  - Proteinases of betaretroviruses bind single-stranded nucleic acids through a
      novel interaction module, the G-patch.
AB  - Retroviral proteinases (PRs) are essential for retrovirus infectivity but the
      mechanism of their activity regulation is poorly understood. We investigated
      possible involvement in this process of the C-terminal domain (CTD) of
      betaretroviral PRs. We found that the presence of CTD attenuates proteolytic
      activity of Mason-Pfizer monkey virus PR, while it does not significantly affect
      the activity of mouse intracisternal A-particle retrovirus PR. However, both PRs
      bind single-stranded nucleic acids through their CTDs that contain a novel
      binding motif, the G-patch, whose function is dependent on a single conserved
      tyrosine residue. Oligonucleotide binding to both PRs does not inhibit their
      proteolytic activity.

PMID- 15474051
TI  - Mutations dislocate caspase-12 from the endoplasmatic reticulum to the cytosol.
AB  - Mouse AKR-2B cells express two forms of caspase-12: the full-length form coding
      for a protein of 47.8 kDa and a new splice variant of 40.2 kDa which is devoid of
      the CARD domain. In addition, three point mutations were disclosed: I/L-15, E/D
      46 and P/L-105. A major portion of the two protein variants was found in the
      cytosol. Immunofluorescence studies showed an even distribution of caspase-12
      within the cell, indicative for a cytoplasmatic localization. Transfection of AKR
      2B cells with wild-type caspase-12 showed a colocalization of this protein with
      the endoplasmic reticulum (ER). Unlike mouse embryonal fibroblasts (MEF) which
      contain wild-type caspase-12, AKR-2B cells were largely resistant against
      treatment with the endoplasmatic reticulum stressing reagents brefeldin and
      tunicamycin. In AKR-2B cells, cytoplasmatic caspase-12 is bound to high molecular
      weight complexes of >1000 kDa [Cell Death Differ. 9 (2001) 125] and serum
      depletion leads to cleavage and detachment of caspase-12 from this high molecular
      weight complex. Cleavage of caspase-12 and -3 occurred almost simultaneously
      reaching a maximum 3-5 h after serum deprivation at which time also maximum
      apoptosis is found. Analysis of caspase-12 cleavage in vitro in comparison with
      fragmentation in vivo suggests that during death in AKR-2B cells induced by
      starvation, cleavage was brought about by caspase-3 at positions D24 and D94.
      Thus, mutated caspase-12 is differently integrated in signaling pathways of cell
      death and has lost its function as initiator caspase upon ER-stress. Instead, it
      is turned into a substrate of effector caspases. The implication of these
      findings in the pathological phenotype of ARK-2B mice is discussed.

PMID- 15474052
TI  - Sequence and structural analysis of kinase ATP pocket residues.
AB  - Protein kinases represent one of the largest known families of enzymes. Most
      kinases bind ATP and most synthetic kinase inhibitors are ATP-competitive, which
      makes selectivity a potential problem. However, despite the high sequence
      similarity in the ATP binding pocket, several groups including ours have been
      able to develop highly potent and selective ATP-competitive inhibitors. To
      systematically aid the design of specific inhibitors in our protein kinase
      projects, we aligned all known three-dimensional structures and all known
      sequences of human protein kinases. We identified a set of 38 residues that make
      up the ATP pocket and analyzed the variability among these residues. The most
      variable residues in the ATP pocket are targeted to design specificity into
      inhibitors in our various kinase projects.

PMID- 15474053
TI  - Synthesis and anti-inflammatory activity of derivatives of 5-[(2
      disubstitutedamino-6-methyl-pyrimidin-4-yl)-sulfanylmethyl]-3H-1,3,4-oxadiazole-2
      thiones.
AB  - Synthesis and results of anti-inflammatory activity in vivo of 5-[(2
      disubstitutedamino-6-methyl-pyrimidin-4-yl)-sulfanylmethyl]-3H-1,3,4-oxadiazole-2
      thiones and their S-alkyl-, N(3)-acyl- and N(3)-aminomethyl derivatives are
      described. All the tested compounds possess anti-inflammatory activity comparable
      to that of acetylsalicylic acid and some derivatives of 5-[(6-methyl-2-piperidin
      1-yl-pyrimidin-4-yl)-sulfanylmethyl]-3H-1,3,4-oxadiazole-2-thione were found to
      be much more active than ibuprofen.

PMID- 15474054
TI  - Synthesis, antitumor and antiviral properties of some 1,2,4-triazole derivatives.
AB  - A series of 1,5-dialkyl-1,2,4-triazole derivatives of acetic acid alkylidene
      hydrazides 8-12, the acid 13, 1,5-dialkyl-3-(5-mercapto-4-N-aryl-1H-[1,2,4]
      triazol-3-ylmethylene)-1H-[1,2,4] triazoles 14-16, their 1,3,4-oxadiazole
      analogues 17-21, as well as the 1,2,4-triazolo-indoles 25 and 27 were prepared.
      The Z/E conformations of some acetic acid alkylidene derivatives were studied by
      NMR spectroscopy. Most of the target compounds were evaluated in a series of
      human cancer cell in cultures and none have shown activity except 25 which
      exhibited remarkable activity against nine cancer types. No in vitro antiviral
      activity against HIV-1, HIV-2, HSV-1, HSV-2, SV, CV-B4, RSV, P3V, RV, SinV, PTV
      has been found for all the synthesized compounds.

PMID- 15474055
TI  - Norchloro-fluoro-homoepibatidine: specificity to neuronal nicotinic acetylcholine
      receptor subtypes in vitro.
AB  - The subtype-specificity of newly synthesised epibatidine-related compounds,
      norchloro-fluoro-homoepibatidine (NCFHEB) and derivatives, to neuronal nicotinic
      acetylcholine receptors (nAChR) has been investigated. NCFHEBs were assayed in
      competitive binding assays to (+/-)-[(3)H]epibatidine-labelled rat thalamic
      nAChRs and human alpha4beta2, alpha3beta4, and alpha7 nAChRs, expressed in stably
      transfected HEK-293 and SH-SY5Y cells. The binding affinity of (+)-NCFHEB (K(i):
      0.064 nM) and (-)-NCFHEB (K(i): 0.112 nM) to human alpha4beta2 nAChR is in the
      same order of magnitude as that of epibatidine (K(i): 0.014 nM). However, because
      the affinity of both NCFHEB-enantiomers to human alpha3beta4 nAChR is up to 65
      times lower than that of epibatidine, the alpha4beta2 subtype-specificity of
      NCFHEB is increased up to 1,400% compared to epibatidine.

PMID- 15474056
TI  - Disposition of 4,6,4'-trimethylangelicin in mice maintained in the dark and after
      UVA irradiation.
AB  - The disposition of the furocoumarin 4,6,4'-trimethylangelicin (4,6,4'-TMA) was
      studied in mice. After oral administration of (3)H 4,6,4'-TMA, radioactivity
      measured in serum shows fast absorption and slow elimination. Serum protein
      binding is higher as compared to 8-methoxypsoralen (8-MOP), currently used in
      photochemotherapy (PUVA) and linearly declines from 30 min to 6 h after
      administration. Distribution in the various organs was similar to that of 8-MOP
      and was relatively uninfluenced by UVA radiation, required for the biological
      effects of 4,6,4'-TMA. Mice eliminate (3)H 4,6,4'-TMA mostly through the urine,
      but also through the faeces. Two metabolites were identified in the urine and
      serum of the treated mice, one of which proved to be a derivative of 4,6,4'-TMA,
      formed by hydrogenation of the double 4',5' bond of the furocoumarin nucleus.

PMID- 15474057
TI  - Sensitive kinetic spectrophotometric determination of captopril and ethamsylate
      in pharmaceutical preparations and biological fluids.
AB  - A highly sensitive kinetic spectrophotometric method was developed for the
      determination of captopril (CPL) and ethamsylate (ESL) in pharmaceutical
      preparations and biological fluids. The method is based on a catalytic
      acceleration of the reaction between sodium azide and iodine in an aqueous
      solution. Concentration range of 0.1-1.5 microg ml(-1) for CPL and 0.3-3 microg
      ml(-1) for ESL was determined by measuring the decrease in the absorbance of
      iodine at 348 nm by a fixed time method. The decrease in absorbance after 5 min
      was markedly correlated to the concentration. The relative standard deviations
      obtained were 1.30 and 1.87 for CPL and ESL, respectively, in pure forms.
      Correlation coefficients were 0.9997 and 0.9999 for CPL and ESL, respectively.
      The detection limits were determined as (S/N = 3) were 20 ng ml(-1) for CPL and
      50 ng ml(-1) for ESL. The proposed procedure was successively applied for the
      determination of both drugs in pharmaceutical preparations and in biological
      fluids.

PMID- 15474058
TI  - Spectrophotometric determination of some fluoroquinolone antibacterials by binary
      complex formation with xanthene dyes.
AB  - Two simple, rapid and sensitive spectrophotometric methods for the determination
      of levofloxacin, norfloxacin and ciprofloxacin have been performed in pure form,
      pharmaceutical tablets and spiked human urine. Both methods are based on the
      formation of a binary complex between the drugs and one of the two xanthene dyes,
      eosin Y or merbromin in aqueous buffered medium. Under the optimum conditions,
      the binary complexes showed absorption maxima at 547 nm for eosin Y and 545 nm
      for merbromin. Using eosin Y, the calibration graph was linear over the range 2-8
      microg ml(-1) for the three drugs with mean percentage recoveries 99.935 +/-
      0.648, 99.973 +/- 0.678 and 100.011 +/- 0.606 for levofloxacin, norfloxacin and
      ciprofloxacin, respectively. While in case of merbromin, the concentration range
      was 2-15 microg ml(-1) with mean percentage recoveries 99.960 +/- 0.491, 100.017
      +/- 0.510 and 99.980 +/- 0.506 for the three drugs, respectively. The proposed
      methods were successfully applied to determine these drugs in their tablet
      formulations and spiked human urine and the results compared favorably to that of
      reference methods. The suggested methods have the advantage of being applicable
      for the determination of the three drugs without prior extraction. They are
      recommended for quality control and routine analysis where time, cost
      effectiveness and high specificity of analytical techniques are of great
      importance.

PMID- 15474059
TI  - The effect of hydrophilic and lipophilic polymers and fillers on the release rate
      of atenolol from HPMC matrices.
AB  - The objective of this study is to investigate the effect of various polymers, and
      fillers, and their concentrations on the release rate of atenolol from polymeric
      matrices. Four polymers namely hydroxypropylmethylcellulose (HPMC), Eudragit
      RSPO, ethylcellulose (EC) and sodium carboxymethylcellulose (NaCMC) were used.
      The dissolution profiles showed that an increase in the concentration of HPMC and
      EC resulted in a reduction in the release rate of atenolol. The results indicate
      that it is difficult to obtain a zero-order release from the matrices containing
      either HPMC or EC. It is also observed that the amount of HPMC played a dominant
      role, affecting the drug release in binary mixtures of Eudragit-HPMC. Generally,
      the presence of NaCMC caused an increase in the release rate of atenolol from
      HPMC matrices. To determine the effect of fillers on the release rate of atenolol
      from HPMC matrices, lactose (a soluble filler) and dicalcium phosphate (an
      insoluble filler) were used. The results showed that an increase in the
      concentration of fillers resulted in an increase in the release rate of the drug
      from matrices and hydrophilicity or hydrophobicity of fillers had no significant
      effect on the release profile. In order to determine the mode of release, the
      data were analysed based on the equation Q = K (t - l)(m). Values of m were in
      the range of 0.32-0.99 indicating that release was controlled by both diffusion
      and erosion, depending on the type of polymer and concentration.

PMID- 15474060
TI  - Determination of methotrexate in pharmaceutical formulations by flow injection
      analysis exploiting the reaction with potassium permanganate.
AB  - A highly sensitive, precise and accurate flow injection procedure for the
      determination of methotrexate (MTX) was described. The method was based on
      oxidation of MTX into highly fluorescence product (2,4-diaminopteridine-6
      carboxylic acid) by acidic potassium permanganate. A three-line manifold was used
      with potassium permanganate as an oxidant (3 mmol l(-1)) and sulfuric acid (6
      mmol l(-1)) as carrier streams. The oxidation process was conducted at 65 degrees
      C through a reaction coil of 3 m (0.5 mm, i.d.). It was essential to eliminate
      the excess of potassium permanganate before passing to the detector using 8 mmol
      l(-1) sodium sulfite as a decolorizing stream. The fluorescence intensity was
      measured at excitation and emission wavelengths of 369 and 465 nm, respectively.
      The calibration graph was linear over the range 40-400 ng ml(-1) MTX. The
      developed method was successfully applied to the determination of MTX in
      pharmaceutical formulations, at a sampling rate of 90 sample h(-1) and showed a %
      recovery ranging from 99.96 to 100.07 and SD% ranging from 0.51 to 0.65%.

PMID- 15474061
TI  - NMR spectroscopy of inclusion complex of D-(-)-chloramphenicol with beta
      cyclodextrin in aqueous solution.
AB  - (1)HNMR spectroscopic study in D(2)O of mixtures of D-(-)-chloramphenicol
      (guest), present in two tautomeric forms in solution, and beta-cyclodextrin
      (host) revealed the formation of 1:1 inclusion complex in which aromatic ring of
      the guest is tightly held by the host cavity. There seems no discrimination
      between the aromatic rings of two tautomers by the host.

PMID- 15474062
TI  - RP-HPLC method and its validation for the determination of naloxone from a novel
      transdermal formulation.
AB  - The aim of the present work was to develop a simple and reliable liquid
      chromatographic method for the quantitative determination of naloxone (NLX) in a
      novel transdermal formulation. Chromatography was carried out by reversed-phase
      technique on a C-18 column with a mobile phase composed of methanol, acetonitrile
      and 50 mM phosphate buffer (pH 7) in the proportion of 40:20:40 v/v/v, at a flow
      rate of 1 ml/min. The UV spectrophotometric determination was performed at 220
      nm. This method was found to be specific and accurate with the mean recovery of
      98.72% in the range of 2-50 microg/ml, and a run time of 15 min (retention time
      of NLX 11.3 min). Method was applied for stability testing of novel transdermal
      formulation developed in our laboratory. Assay content of NLX in the formulation
      was determined in stability samples and compared with the control samples.
      Statistical analysis by Student's t-test showed no significant difference between
      the assay content of NLX in control and test samples at 95% confidence interval.
      Overall, the proposed method is highly sensitive, precise and accurate and can be
      used for the reliable quantitation of NLX in developed transdermal formulation
      with the added advantage of simple procedure.

PMID- 15474063
TI  - Spectrophotometric determination of metronidazole and secnidazole in
      pharmaceutical preparations.
AB  - A rapid and sensitive spectrophotometric method is proposed for determination of
      metronidazole and secnidazole. The method depends on the reduction of
      metronidazole and secnidazole molecule with zinc dust and hydrochloric acid
      flowed by diazotization and coupling with 8-quinolinol to give red colored
      chromogens easily measured spectrophotometrically which has lambda(max) = 500 nm.
      The experimental conditions were optimized and Berr's law was obeyed over the
      applicable concentration ranges both techniques were applied successfully to a
      wide variety of pharmaceutical preparations.

PMID- 15474064
TI  - The presence of endometrial cells in the peritoneal cavity enhances monocyte
      recruitment and induces inflammatory cytokines in mice: implications for
      endometriosis.
AB  - OBJECTIVE: To determine the inflammatory response in the peritoneal cavity by the
      presence of endometrial cells and the role of the mesothelium. DESIGN: In vivo
      study using mice. SETTING: University research laboratory. ANIMAL(S): Female
      Swiss Webster mice, 8 to 10 weeks old. INTERVENTION(S): Homogenous mouse
      endometrial epithelial and stromal cells were injected intraperitoneally.
      Peritoneal lavage and mesothelium were collected 4 to 72 hours after the
      administration. MAIN OUTCOME MEASURE(S): We determined the number of peritoneal
      macrophages, and the production and gene expression of monocyte chemotactic
      protein-1 (MCP-1/JE), interleukin 1alpha (IL-1alpha), and interleukin 6 (IL-6).
      RESULT(S): The intraperitoneal administration of endometrial cells increased the
      number of peritoneal macrophages, production of MCP-l, IL-1alpha, and IL-6, and
      expression of mesothelial MCP-1/JE, IL-1alpha, and IL-6 genes in recipient mice.
      CONCLUSION(S): These results suggest that retrograde menstruation could account
      for the increased presence of inflammatory mediators in the peritoneal cavity of
      women with endometriosis. The mesothelium could play an active role in
      endometriosis in addition to providing an attachment stratum for the endometrial
      cells.

PMID- 15474065
TI  - Peroxisome proliferator-activated receptor-gamma induces regression of
      endometrial explants in a rat model of endometriosis.
AB  - OBJECTIVE: To determine the effects of a thiazolidinedione, ciglitazone, in a rat
      model of endometriosis. DESIGN: Prospective, randomized, placebo-controlled
      study. SETTING: Experimental surgery laboratory in a university department.
      ANIMAL(S): Twenty female Sprague-Dawley rats given endometriotic lesions by
      transplanting autologous uterine tissue to ectopic sites on the peritoneum.
      INTERVENTION(S): Four weeks after surgery, 20 rats were randomly divided into two
      groups and treated with IP injections of vehicle every other day (control; n =
      10) or ciglitazone (1 mg per rat; n = 10) and euthanized 4 weeks from the start
      of treatment. MAIN OUTCOME MEASURE(S): At the end of treatment, laparotomy was
      performed to photograph each explant and then they were measured and weighed.
      Histologic analysis was performed on the uterine allograft, ovary, and eutopic
      uterine tissue. RESULT(S): By histologic assessment, both groups maintained
      folliculogenesis and normal eutopic endometrial architecture. Treatment with
      ciglitazone significantly decreased the size of ectopic uterine tissues and the
      mean explant wet weight. The ciglitazone-treated group showed marked epithelial
      regression compared with the control group. CONCLUSION(S): We conclude that a
      PPAR-gamma ligand, ciglitazone, reduced the size of experimental endometriosis in
      the rat model of endometriosis. This animal model suggests that a
      thiazolidinedione drug may be helpful in women with endometriosis.

PMID- 15474066
TI  - Cultured human endometrial epithelial cells produce thymus and activation
      regulated chemokine with stimulation of interleukin-4 and interleukin-13.
AB  - OBJECTIVE: To evaluate the effects of T-helper (Th)1 and Th2 cytokines on the
      production of thymus and activation-regulated chemokine (TARC) and macrophage
      derived chemokine (MDC) by cultured endometrial epithelial cells (EEC) and
      endometrial stromal cells (ESC). DESIGN: The effects of interleukin (IL)-2, IL-4,
      IL-5, IL-10, IL-12, IL-13, interferon-gamma (IFN-gamma), and tumor necrosis
      factor-beta (TNF-beta) on the production of TARC and MDC were investigated.
      SETTING: Research laboratory at a medical school. PATIENT(S): Fifteen endometrial
      specimens in the mid-late secretory phase were used. INTERVENTION(S): The EEC and
      ESC were incubated for 24 hours with recombinant human IL-2, IL-4, IL-5, IL-10,
      IL-12, IL-13, IFN-gamma, and TNF-beta. MAIN OUTCOME MEASURE(S): The
      concentrations of TARC and MDC in the culture media were measured using ELISA.
      RESULT(S): Small amounts of TARC were detected in the culture medium of
      nonstimulated EEC. The increase in levels of TARC in the culture media of EEC
      paralleled the addition of increasing amounts of IL-4 and IL-13. Other cytokines,
      however, did not affect the production of TARC by EEC. Production of TARC by ESC
      was not detected under either nonstimulated or cytokine-stimulated conditions.
      Production of MDC was not detected in the culture media of EEC and ESC.
      CONCLUSION(S): These results suggest that IL-4 and IL-13 secreted from the embryo
      during the implantation period may selectively up-regulate the production of TARC
      by EEC. The controlled production of TARC in the endometrium may contribute to
      the modulation of the immune reaction by the regulation of Th2 lymphocyte
      trafficking and functions.

PMID- 15474067
TI  - Effects of oxidants and antioxidants on proliferation of endometrial stromal
      cells.
AB  - OBJECTIVE: To evaluate the effects of oxidative stress and antioxidants on
      proliferation of endometrial stromal cells. DESIGN: In vitro study. SETTING:
      Academic laboratory. PATIENT(S): Women, with and without endometriosis, of
      reproductive age. INTERVENTION(S): Culture of endometrial stromal cells with
      antioxidants or with agents inducing oxidative stress. MAIN OUTCOME MEASURE(S):
      Proliferation of endometrial stromal cells as determined by thymidine
      incorporation assay and 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium
      bromide (MTT) assay. RESULT(S): Antioxidants induced a dose-dependent inhibition
      of thymidine incorporation: vitamin E succinate was inhibitory at 10-100 microM
      (by 43%-95%), ebselen at 10-30 microM (by 29%-77%), and N-acetylcysteine at 10-30
      mM (by 52%-85%). In contrast, modest oxidative stress induced by
      hypoxanthine/xanthine oxidase (1 mM/3-30 microU/mL) stimulated proliferation by
      40%-62%. H2O2 (1 microM) increased DNA synthesis by 56%. Comparable findings were
      obtained using MTT proliferation assay. Antioxidants inhibited proliferation:
      vitamin E succinate (100 microM) by 91%, ebselen (30 microM) by 81%, and N
      acetylcysteine (30 mM) by 95%. Hypoxanthine/xanthine oxidase (1 mM/30 microU/mL)
      and H2O2 (1 microM) stimulated growth by 122% and 58%, respectively.
      CONCLUSION(S): Reactive oxygen species may modulate growth of endometrial stroma.
      Under pathologic conditions such as endometriosis, increased oxidative stress and
      depletion of antioxidants may contribute to excessive growth of endometrial
      stromal cells.

PMID- 15474068
TI  - Tumor necrosis factor-alpha induced the release of interleukin-6 from
      endometriotic stromal cells by the nuclear factor-kappaB and mitogen-activated
      protein kinase pathways.
AB  - OBJECTIVE: To examine the involvement of nuclear factor-kappaB (NF-kappaB) and
      mitogen-activated protein kinase (MAPK) in the induction of interleukin-6 (IL-6)
      by tumor necrosis factor-alpha (TNF-alpha) in endometriotic stromal cells (ESC).
      DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology,
      Tottori University Hospital, Yonago, Japan. PATIENT(S): Twelve patients who
      underwent laparoscopic surgery. INTERVENTION(S): Endometriotic stromal cells were
      obtained from chocolate cyst linings of the ovary. MAIN OUTCOME MEASURE(S): We
      determined the effect of TNF-alpha on the production of IL-6 and the effect of
      inhibitors for NF-kappaB and the MAPK pathway on IL-6 production using ELISA.
      Western blottings and electrophoretic mobility shift assays were used to detect
      activation of NF-kappaB and extracellular signal-regulated kinase 1/2 (ERK1/2).
      RESULT(S): The addition of TNF-alpha (0.1 ng/mL) significantly increased IL-6
      protein in endometriotic stromal cells. Western blottings and electrophoretic
      mobility shift assays revealed that incubation with TNF-alpha induced degradation
      of inhibitor kappaB (I kappaB) and expression of phosphorylated ERK1/2. The NF
      kappaB inhibitor (TPCK) and MAPK inhibitor (U0126) blocked the TNF-alpha-induced
      IL-6 expression. Electrophoretic mobility shift assay revealed that U0126
      attenuated activator protein-1 (AP-1) activation induced by TNF-alpha.
      CONCLUSION(S): These findings demonstrate that NF-kappaB and AP-1 activation is
      critical for TNF-alpha-induced IL-6 expression in endometriotic stromal cells.
      Novel therapeutic modalities targeting these molecules may be possible in the
      near future.

PMID- 15474069
TI  - Early embryo-endometrial signaling modulates the regulation of matrix
      metalloproteinase-3.
AB  - OBJECTIVE: To examine matrix metalloproteinase-3 (MMP-3) expression in human
      stromal cell culture after P stimulation and the effect of conditioned medium
      from human embryo-epithelial cells coculture on its expression and activity.
      DESIGN: Metabolic and endocrine studies on human tissue. SETTING: In vitro
      fertilization (i.v.f.) unit and endocrine research unit. PATIENT(S): Infertile
      patients undergoing endometrial tissue sampling for dating at the luteal phase
      before i.v.f. INTERVENTION(S): Endometrial sampling and collection of human
      embryos culture media. MAIN OUTCOME MEASURE(S): Expression and activity of
      secreted MMP-3 by P-induced stromal cells, and in stromal cells exposed to
      conditioned medium from embryo-epithelial cell coculture. RESULT(S): Expression
      and activity of MMP-3 in human stromal cells decrease after P induction.
      Following incubation of these stromal-derived decidual cells with conditioned
      medium from embryo-epithelial cell coculture, MMP-3 expression and activity
      increased in a statistically significant manner. CONCLUSION(S): Progesterone
      inhibition of MMP-3 expression and its support of endometrial integrity were
      prevented by local expression of MMP-3 in response to embryonic signaling.

PMID- 15474070
TI  - Lipopolysaccharide-promoted proliferation of endometriotic stromal cells via
      induction of tumor necrosis factor alpha and interleukin-8 expression.
AB  - OBJECTIVE: To evaluate the effect of lipopolysaccharide (LPS) on the expression
      of tumor necrosis factor alpha (TNFalpha) and interleukin-8 (IL-8) protein in
      endometriotic stromal cells (ESC) and their effect on the proliferation of ESC.
      DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology,
      Tottori University Hospital, Yonago, Japan. PATIENT(S): Seventeen patients who
      underwent laparoscopic surgery. INTERVENTION(S): Endometriotic stromal cells were
      obtained from chocolate cyst linings of the ovary. MAIN OUTCOME MEASURE(S): We
      determined the effect of LPS on the production of TNFalpha and IL-8 and the
      effect of IL-8 antisense oligonucleotide and nuclear factor-kappaB (NF-kappaB)
      inhibitor on IL-8 production using ELISA. TNFalpha production was examined by
      immunocytochemical staining. We determined the effect of LPS and the effect of IL
      8 antisense oligonucleotide and NF-kappaB inhibitor on LPS-promoted ESC
      proliferation. RESULT(S): LPS-stimulated ESC produced significant amounts of
      TNFalpha and IL-8 in a dose- and time-dependent fashion. Adding LPS promoted ESC
      proliferation. Anti-TNFalpha antibody and anti-IL-8 antibody inhibited the
      stimulatory effects of LPS. IL-8 antisense oligonucleotide and NF-kappaB
      inhibitor significantly decreased LPS-induced IL-8 protein production and LPS
      induced ESC proliferation. CONCLUSION(S): Pelvic inflammation may promote the
      progression of endometriosis.

PMID- 15474071
TI  - Synergistic effect of interleukin (IL)-1alpha and ceramide analogue on the
      production of IL-6, IL-8, and macrophage colony-stimulating factor by endometrial
      stromal cells.
AB  - OBJECTIVE: To measure the level of interleukin 6 (IL-6), IL-8, and macrophage
      colony-stimulating factor (M-CSF) induced by IL-1alpha in endometrial stromal
      cells (ESC) following treatment with ceramide analogues. DESIGN: The effects of
      IL-1alpha, IL-1 receptor antagonist (IL-1RA), C2-ceramide, and C6-ceramide on the
      production of IL-6, IL-8, and M-CSF by ESC. SETTING: Research laboratory at Oita
      University Medical School. PATIENT(S): Eleven premenopausal women who had
      undergone hysterectomies for subserous myoma provided endometrial specimens in
      the secretory phase. INTERVENTION(S): The ESC were incubated for 24 hours with IL
      1alpha, IL-1RA, C2-ceramide, and C6-ceramide. MAIN OUTCOME MEASURE(S): The levels
      of IL-6, IL-8, and M-CSF in the culture media were measured via enzyme-linked
      immunoabsorbent assay. RESULT(S): : Following stimulation by IL-1alpha, the
      production of IL-6, IL-8, and M-CSF showed a statistically significant increase,
      and they were suppressed by IL-1RA in a dose-dependent manner. Production of IL
      6, IL-8, and M-CSF was not statistically significantly increased by IL-1alpha
      plus C2-ceramide as compared with IL-1alpha alone. Production of both IL-8 and M
      CSF was statistically significantly increased by IL-1alpha plus C6-ceramide as
      compared with IL-1alpha alone; however, IL-6 production was not increased.
      CONCLUSION(S): The results suggest that IL-1alpha stimulates the production of IL
      8 and M-CSF by a mechanism that involves the sphingomyelin-ceramide system.
      Ceramide may be important in increasing the production of IL-8 and M-CSF in the
      human endometrium.

PMID- 15474072
TI  - Modulation of vascular endothelial growth factor and thymidine phosphorylase in
      normal human endometrial stromal cells.
AB  - OBJECTIVE: To study the regulation of vascular endothelial growth factor (VEGF)
      and thymidine phosphorylase (TP), two angiogenic factors, in cultured endometrial
      stromal cells. The effects of steroids, E2, and P, the gonadotropin, hCG, and
      hypoxia were investigated. DESIGN: Quantitative experimental study. SETTING:
      Academic medical department. PATIENT(S): Women undergoing hysterectomy for benign
      causes. INTERVENTION(S): Endometrial cells were collected from subjects and
      cultured. MAIN OUTCOME MEASURE(S): The secretion of VEGF in supernatant media and
      the numbers of cells expressing VEGF or TP. RESULT(S): Estradiol increased VEGF
      secretion and the number of cells that contained VEGF and TP, and those effects
      were inhibited by hCG. Human chorionic gonadotropin alone could increase number
      of cells that expressed VEGF and TP. Hypoxia increased both VEGF secretion and
      number of cells containing VEGF and TP. Progesterone had no observed effect on
      VEGF secretion or number of VEGF- or TP-containing cells. CONCLUSION(S): Vascular
      endothelial growth factor and TP are present in stromal cells of normal
      endometrium, and E2 may interact with gonadotropins to regulate angiogenic
      compounds to modulate stromal functioning.

PMID- 15474073
TI  - Sperm-immobilizing antibodies suppress an increase in the plasma membrane
      fluidity of human spermatozoa.
AB  - OBJECTIVE: To clarify the mechanism by which capacitation is blocked by sperm
      immobilizing antibodies, changes in the plasma membrane fluidity of human
      spermatozoa exposed to sperm-immobilizing antibodies were evaluated. DESIGN: In
      vitro cell culture study using human spermatozoa. SETTING: Department of
      Obstetrics and Gynecology, School of Medicine, The University of Tokushima.
      PATIENT(S): Semen samples were obtained from four healthy, fertile volunteers.
      INTERVENTION(S): The internalization of [3H]lyso-platelet activating factor (lyso
      PAF) across the plasma membranes of human spermatozoa, which were exposed to
      sperm-immobilizing antibodies (antisperm group) or not exposed (control group),
      was measured at 20 and 60 minutes after the addition of a phospholipid probe
      using the modified albumin-back extraction method. MAIN OUTCOME MEASURE(S): The
      percentage of internalization of [3H]lyso-PAF across the plasma membrane of human
      spermatozoa. RESULT(S): Although the percentages of internalization of [3H]lyso
      PAF (mean +/- SE) in the antisperm and control groups 20 minutes after addition
      of [3H]lyso-PAF were not significantly different (6.6% +/- 1.5% and 9.2% +/-
      2.1%, respectively), at 60 minutes after the addition, the percentage in the
      antisperm group (9.0% +/- 1.3%) was significantly lower than that in the control
      group (13.4% +/- 1.3%). This inhibitory effect was diminished when spermatozoa
      exposed to sperm-immobilizing antibodies were incubated in an antibody-free
      medium. CONCLUSION(S): Sperm-immobilizing antibodies suppress the increase in
      internalization of an alkyl ester lysophospholipid probe in plasma membranes of
      human spermatozoa, and this inhibitory effect is reversible. Therefore, sperm
      immobilizing antibodies suppress the fluidity of the plasma membranes of human
      spermatozoa, thus blocking capacitation.

PMID- 15474075
TI  - Association of male infertility with Pro185Ala polymorphism in the aryl
      hydrocarbon receptor repressor gene: implication for the susceptibility to
      dioxins.
AB  - OBJECTIVE: To examine whether Arg554Lys polymorphism in the gene for aryl
      hydrocarbon receptor (AHR) and/or Pro185Ala polymorphism in the gene for aryl
      hydrocarbon receptor repressor (AHRR) constitutes a susceptibility locus for
      dioxin-related male infertility. DESIGN: Association study of male infertility
      with polymorphisms. SETTING: National research institute and university
      hospitals. PATIENT(S): 123 Japanese men with azoospermia or severe
      oligozoospermia and 112 men with proven fertility. INTERVENTION(S): Polymorphism
      analysis. MAIN OUTCOME MEASURE(S): The allele and genotype frequencies between
      infertile men and controls. RESULT(S): The allele and genotype frequencies of the
      AHR polymorphism were comparable between infertile men and controls. By contrast,
      although the difference in the allele frequency of the AHRR polymorphism did not
      reach a significant level, the genotype frequency was statistically significantly
      different between the two groups of men. Furthermore, the statistical difference
      became more significant when the frequency was compared between the Pro/Pro
      genotype and the Pro/Ala plus Ala/Ala genotype. CONCLUSION(S): The Pro185Ala
      polymorphism in AHRR may constitute a susceptibility locus for dioxin-related
      male infertility. It appears that the negative feedback effect of AHRR on dioxin
      related signaling is weaker for the proline allele than for the alanine allele,
      and that the hypomorphic function of the proline allele exerts a recessive
      adverse effect on male fertility.

PMID- 15474074
TI  - Relationship among standard semen parameters, glutathione peroxidase/glutathione
      reductase activity, and mRNA expression and reduced glutathione content in
      ejaculated spermatozoa from fertile and infertile men.
AB  - OBJECTIVE: To determine the expression and enzymatic activity of glutathione
      peroxidase (GPX)-1, GPX-4, and glutathione reductase together with glutathione
      (GSH) concentrations in spermatozoa from fertile and infertile men. DESIGN:
      Prospective study. SETTING: University-affiliated private center. PATIENT(S):
      Fifty-four infertile men undergoing assisted reproduction techniques and 55
      fertile sperm donors with pregnancies and newborns by artificial insemination.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Analysis of gene expression by
      fluorescent quantitative polymerase chain reaction and an analysis of enzymatic
      activity and GSH concentration by controlled biochemical reactions and
      spectrophotometry. RESULT(S): GPX-4 activity but not mRNA expression is directly
      related to sperm morphology (strict criteria) and is more compromised with a low
      percentage of normal sperm. These differences are also demonstrated when fertile
      and infertile men were compared. In addition, intracellular GSH concentrations
      are lower when sperm morphology is severely impaired, but no differences were
      found between fertile and infertile men. CONCLUSION(S): Intracellular sperm GSH
      system components GPX-4 and GSH are altered in infertile men, and these
      alterations seem to be linked to sperm morphology.

PMID- 15474076
TI  - Normal expression of isoforms activating cyclic adenosine monophosphate
      responsive element modulator in patients with spermatid maturation arrest.
AB  - OBJECTIVE: To evaluate whether defective cyclic adenosine monophosphate
      responsive element modulator (CREM) expression is the causative factor of
      spermatid maturation arrest (SMA). DESIGN: Comparative evaluation of the
      testicular histology in patients with SMA or normal spermatogenesis. SETTING:
      University clinic of andrology. PATIENT(S): Azoospermic patients undergoing
      testicular biopsy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Expression of
      CREMtau in quantitative immunohistochemistry analysis of testicular biopsy
      samples. RESULT(S): Regular CREM expression was observed in the tubules with
      round, but not elongated, spermatids of patients with SMA (n = 9). Quantitative
      analysis showed that round spermatids of patients with SMA had a staining
      intensity similar to that observed in controls (n = 7). CONCLUSION(S): Lack of
      spermatid elongation was not due to defective CREM expression. Therefore, CREM
      did not play a pathogenetic role in the onset of SMA in humans.

PMID- 15474077
TI  - Effects of testosterone, dihydrotestosterone, and 17beta-estradiol on human
      ovarian tissue survival in culture.
AB  - OBJECTIVE: To investigate the effects of T, dihydrotestosterone (DHT), and 17beta
      estradiol on human ovarian stromal tissue survival in culture and to identify
      steroids capable of inhibiting cell death in vitro. DESIGN: Prospective study.
      SETTING: Academic research setting. PATIENT(S): Thirty women, aged 18-38 years,
      undergoing gynecological operations for benign conditions and eight women, aged
      27-36 years, undergoing IVF because of tubal obstruction or male factor
      infertility. INTERVENTION(S): Cultured tissue was exposed to T, DHT, 17beta
      estradiol, or the anti-androgen casodex. MAIN OUTCOME MEASURE(S):
      Immunohistochemistry for androgen receptor (AR), Southern blot analysis of DNA
      fragmentation, histology, and in situ end labeling of apoptotic DNA. RESULT(S):
      Androgen receptors were detected in the ovarian stroma and granulosa cells of the
      primordial follicles, although they were more clearly seen in primary follicles
      and more advanced-stage follicles. Testosterone only marginally suppressed
      ovarian tissue apoptosis in vitro. DHT was more effective than T, whereas 17beta
      estradiol had no notable effect on the viability of the tissue. The effects of
      androgens on the ovarian tissue may be mediated through ARs, since blocking the
      receptors with an AR antagonist reversed the suppressive effect of DHT.
      CONCLUSION(S): DHT may be useful for enhancing human ovarian tissue survival in
      vitro.

PMID- 15474078
TI  - Human follicular fluid stimulates the sperm acrosome reaction by interacting with
      the gamma-aminobutyric acid receptors.
AB  - OBJECTIVE: To evaluate whether gamma-aminobutyric acid receptors are involved in
      human sperm acrosome reaction induced by the follicular fluid (FF). DESIGN:
      Random selection of normal sperm samples. SETTING: Normal men in an university
      clinic of andrology. PATIENT(S): Men with normal sperm analysis parameters.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Acrosome reaction on motile
      spermatozoa. RESULT(S): Follicular fluid stimulated the acrosome reaction dose
      dependently. The effect of a maximally effective concentration of FF (30%,
      vol/vol) was significantly suppressed by bicuculline, a GABAA receptor
      antagonist, and saclofen, a GABAB receptor antagonist, added concomitantly. Each
      of the two antagonists used alone was devoid of effect. Because the GABAA
      receptor is linked to the chloride channel, we tested whether picrotoxin, a
      blocker of this channel, could modulate the effects of the FF. Picrotoxin alone
      did not have any effect on the acrosome reaction induced by the FF, whereas it
      had a significant suppressive effect if coincubated with saclofen. The acrosome
      reaction induced by the FF was also inhibited by picrotoxin plus verapamil, a
      calcium channel blocker, whereas verapamil alone had no significant effect. This
      suggested that both chloride and calcium ions mediated the acrosome reaction
      induced by the FF. CONCLUSION(S): The simultaneous blockade of GABAA and GABAB
      receptors suppressed the acrosome reaction induced by the FF. This finding
      suggested that GABA receptors play a physiologic role in sperm activation and
      shed further light on the mechanism of FF action on human sperm acrosome
      reaction.

PMID- 15474079
TI  - Adenomyosis in the baboon is associated with primary infertility.
AB  - OBJECTIVE: To determine whether an association exists between the histopathologic
      diagnosis of adenomyosis and infertility in a population of captive baboons.
      DESIGN: Case-control study. SETTING: Southwest National Primate Research Center.
      ANIMAL(S): Necropsy records of 37 baboons diagnosed with adenomyosis uteri and 38
      baboons with normal uterine histology. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Chi2 analysis of the association between adenomyosis, primary
      infertility, and the presence of coexisting endometriosis. RESULT(S):
      Endometriosis was associated with the presence of adenomyosis (OR = 31.5, 95% CI
      4.2-1,348). There was a trend toward an association of endometriosis with the
      presence of lifelong infertility, but this correlation did not quite achieve
      statistical significance (OR = 3.6, 95% CI 0.9-15.8). Adenomyosis was associated
      with the presence of lifelong infertility (OR = 20.6, 95% CI 2.7-897). This
      association was maintained when cases of coexisting endometriosis (n = 17) were
      excluded (OR = 20.1, 95% CI 2.1-921). CONCLUSION(S): Adenomyosis is strongly
      associated with lifelong primary infertility in the baboon, even in the absence
      of coexisting endometriosis.

PMID- 15474080
TI  - Alternation of cytosolic carbonic anhydrase isoenzymes during deciduomatal
      development in pregnant mice.
AB  - OBJECTIVE: To analyze the activity of cytosolic carbonic anhydrases (CAs) during
      the pre- and postimplantation stages of pregnancy in mice. Furthermore, to
      investigate the CA activity in mice in which abortion was induced by injection of
      substance P. DESIGN: Controlled animal experiment. SETTING: University research
      laboratory. ANIMAL(S): A total of 75 ICR mice (weight between 20-25 g) that
      showed two consecutive 4-day cycles. INTERVENTION(S): Substance P (2.4 microg/g)
      or CA inhibitor (100 microg/g), or both, were administered. Decidualized uterine
      tissues were collected on days 0.5-10.5 after administration. MAIN OUTCOME
      MEASURE(S): The activity, protein expression pattern, and mRNA level of decidual
      cytosolic CAs. RESULTS: The abortion induced by injection of substance P led to
      an aberrant expression of cytosolic CA and a decreased number of embryos.
      Furthermore, substance P-induced abortion could be effectively inhibited by CA
      inhibitors. CONCLUSIONS: Cytosolic CAs, especially CA II, may act as negative
      regulators in implantation, development, and maintenance of the pregnancy and
      therefore, this information could be further applied in developing therapies for
      human sterility.

PMID- 15474081
TI  - Direct injection of vascular endothelial growth factor into the ovary of mice
      promotes follicular development.
AB  - OBJECTIVE: To investigate the effects of an ovarian injection of vascular
      endothelial growth factor (VEGF) on antral follicle development, neoangiogenesis,
      and apoptosis. DESIGN: Controlled laboratory study. SETTING: University
      affiliated fertility center. ANIMAL(S): Balb/c female mice (n = 32) were studied.
      INTERVENTION(S): Mice were divided into four groups: control group (C) n = 6, no
      treatment; hyperstimulated group (HS), n = 8, ovaries were stimulated with 7.5 IU
      pregnant mare serum gonadotropin (PMSG) and 10 IU of hCG; VEGF group (V), n = 8,
      injected with 0.1 mL of VEGF (0.2 microg) in each ovary; V+HS, n = 8 injected
      with VEGF and 2 weeks later hyperstimulated. MAIN OUTCOME MEASURE(S): Number of
      antral and luteinized follicles, number of vessels, and percentage of Bcl-2
      positive cells. RESULT(S): The number of antral follicles with VEGF was higher
      than in the C and HS groups (16.0 +/- 2.5 vs. 6.0 +/- 0.9 and 11.3 +/- 0.6,
      respectively, p<0.005). All treatments significantly increased the number of
      vessels (C: 5.0 +/- 0.5 vs. V: 20.0 +/- 4.8, p<0.005 and V+HS: 22.2 +/- 1.2,
      p<0.01), as well as increased Bcl-2-positive cells compared to controls (C: 0; V:
      11.8 +/- 3.5, p<0.005; V+HS: 12.5 +/- 3.7, p<0.005). CONCLUSION(S): Our findings
      demonstrated that a direct injection of VEGF into the mouse ovary results in the
      development of an enhanced vascular network promoting follicular development and
      diminishing apoptosis.

PMID- 15474082
TI  - A two-generation reproduction study to assess the effects of cows' milk on
      reproductive development in male and female rats.
AB  - OBJECTIVE: To examine whether the considerable quantities of increased female sex
      hormone levels found in modern milk as a result of modern dairy farming practices
      are safe for human consumption. DESIGN: Males and females of the P generation
      were maintained on a diet containing milk for 10 weeks before mating. Exposure to
      milk was continued up to the end of weaning of the F2b offspring. SETTING: Two
      generation reproduction study. ANIMAL(S): Male and female Wistar Galas rats.
      INTERVENTION(S): P- and F1-generation rats were mated. MAIN OUTCOME MEASURE(S):
      Fertility, fecundity, and morphology and function of reproductive organs.
      RESULT(S): Although milk had growth-promoting effects in both parents and
      offspring, it caused no impairments in fertility, fecundity, or reproductive
      organ development in either generation. However, a whole litter from a dam of the
      P generation was born dead, three litters in total had a pup with skeletal
      abnormalities, and the AGD of F2a female pups was reduced. These events occurred
      only in the milk-treated rats. It is unknown whether these issues had any
      relevance to milk or only happened by chance. CONCLUSION(S): Further study is
      required to determine whether milk from pregnant cows is completely free from
      adverse effects on reproductive health.

PMID- 15474083
TI  - Regression of endometrial explants in rats treated with the cyclooxygenase-2
      inhibitor rofecoxib.
AB  - OBJECTIVE: To investigate the effects of cyclooxygenase-2 (COX-2) inhibitor
      rofecoxib on endometrial explants and on peritoneal vascular endothelial growth
      factor (VEGF) levels in the rat endometriosis model. DESIGN: Prospective, placebo
      controlled study. SETTING: Laboratory at Dokuz Eylul University. ANIMAL(S):
      Twenty-six rats with experimentally induced endometriosis. INTERVENTION(S): Rats
      were treated for 3 weeks with oral rofecoxib (3 mg/kg per day; n = 9); single
      subcutaneous injection of depot leuprolide acetate (1 mg/kg; n = 9); or vehicle
      (control; n = 8). MAIN OUTCOME MEASURE(S): Change in explant area and histologic
      examination by semiquantitative analysis of endometriotic explants and
      measurement of peritoneal VEGF levels. RESULT(S): Three weeks of treatment with
      rofecoxib statistically significantly decreased the implant size (62.4%) compared
      with control (16.6%), and this effect was comparable with the decrease in
      leuprolide (64.3%). Histologic examination of the explants indicated mostly
      atrophy and regression in treatment groups, and semiquantitative analysis showed
      statistically significantly lower scores in rats treated with rofecoxib and
      leuprolide compared with controls. Both rofecoxib and leuprolide statistically
      significantly decreased VEGF levels compared with controls. CONCLUSION(S):
      Rofecoxib causes regression and atrophy of the endometriotic lesions and is as
      effective as a GnRH agonist with an accompanying decrease in the VEGF levels.

PMID- 15474084
TI  - Morphometric changes in the endometrium and serum leptin levels during the
      implantation period of the embryo in the rat in response to exogenous ovarian
      stimulation.
AB  - OBJECTIVE: To determine the changes in endometrium and serum leptin levels during
      the periimplantation period of the ovum in the rat in response to exogenous
      ovarian stimulation by hMG and recombinant FSH (rFSH). DESIGN: Experimental
      animal study. SETTING: University hospital. INTERVENTION(S): A total of 100
      female rats were stimulated with low and high doses of hMG (groups 1 and 2,
      respectively) and low and high doses of rFSH (groups 3 and 4, respectively)
      before mating after the regular cycle was observed. The control group of animals
      was not injected (group 5). The endometrium of the pregnant rats (n = 53) was
      analyzed by the morphometric method, and serum samples were obtained for leptin
      and E2 levels at baseline and on the day of implantation. The mitotic index was
      determined separately for endometrial surface, glandular epithelium, and
      endometrial stroma by light microscope. MAIN OUTCOME MEASURE(S): Morphometric
      analysis of endometrium, mitotic index, and serum leptin and E2 levels RESULT(S):
      The mean number of corpora lutea was significantly higher in groups 2 and 4. The
      measurement of mucosal depth was found to be significantly higher in group 4
      compared with the control group (0.361 +/- 0.03 vs. 0.289 +/- 0.04). The depth of
      the endometrial surface epithelium was found to be significantly higher in all
      study groups (groups 1-4) compared with the control group. The depth of the
      surface epithelium was found to be significantly lower in group 1 compared with
      the other study groups (groups 2, 3, and 4). The depth of the surface epithelium
      was also significantly lower in group 2 compared with group 3 (21.58 +/- 3.56 vs.
      28.21 +/- 3.56). Mitotic indices that were determined at the endometrial surface
      epithelium and stroma were all significantly lower in all study groups (groups 1
      4) compared with the control group. There was no significant increase for the
      baseline leptin levels compared with the levels measured on the day of
      implantation. CONCLUSION(S): In an animal model, exogenous administration of
      gonadotropins significantly affects the morphology of the endometrium and the
      mitotic index in the implantation period of the embryo. These morphological
      effects become more pronounced as we increase the administered dose of exogenous
      gonadotropins. However, no differences in leptin levels were observed relative to
      different gonadotropin type and dose regimens.

PMID- 15474085
TI  - Effect of angiotensin-converting enzyme-inhibiting therapy on the expression of
      vascular endothelial growth factor in hyperstimulated rat ovary.
AB  - OBJECTIVE: To determine the effect of angiotensin-converting enzyme-inhibiting
      therapy on the expression of vascular endothelial growth factor (VEGF) in the
      hyperstimulated rat ovary. DESIGN: Experimental study. SETTING: University animal
      research laboratory. ANIMAL(S): Thirty Wistar albino adult female rats were
      studied; 20 rats were stimulated with gonadotropins (groups 1 and 2), and 10 were
      controls (group 3). Ten of the stimulated rats received additional treatment with
      enalapril (group 2). INTERVENTION(S): At the end of the treatment period, rat
      ovaries were subjected to immunohistochemical staining with anti-VEGF antibodies.
      MAIN OUTCOME MEASURE(S): VEGF staining intensity was graded semiquantitatively,
      and the H-score was calculated by light microscopic examination of the groups.
      RESULT(S): VEGF expression was found to be significantly higher in the
      endothelium and stroma in groups 1 and 2 compared with group 3. Although VEGF
      immunoreactivity was lower in the stimulation regimen plus enalapril group
      compared with the stimulation regimen-only group, the difference was
      insignificant. CONCLUSION(S): Enalapril does not seem to have a significant
      effect on VEGF expression in the hyperstimulated rat ovary. Because angiotensin
      II exerts its multiple actions via specific receptors, there may be other
      factors, such as a receptor blockade, that contribute to the VEGF expression.

PMID- 15474086
TI  - Norgestimate and medroxyprogesterone acetate do not attenuate the
      atheroprotective effects of 17beta-estradiol in ovariectomized, apolipoprotein E
      deficient mice.
AB  - OBJECTIVE: To determine whether progestins counteract the cardioprotective
      effects of estrogen. DESIGN: Controlled animal study. SETTING: Academic
      laboratory environment. ANIMAL(S): Female apolipoprotein E-deficient mice.
      INTERVENTION(S): Mice were randomly assigned to groups receiving a sham operation
      plus placebo pellet, bilateral gonadectomy plus placebo pellet, or gonadectomy
      plus one of nine combinations of estrogen/progestin SC pellets. MAIN OUTCOME
      MEASURE(S): Total plasma cholesterol, body weight, fat depot weight, uterine
      weight and size, and the cross-sectional area of fatty streaks in the aortic
      sinus were measured in each animal. RESULT(S): After 8 weeks of treatment, plasma
      cholesterol levels were significantly higher only in the ovariectomized and sham
      operated animals that received placebo pellets. No differences in plasma
      cholesterol were observed relative to the type or amount of progestin
      administered. There was a reduction in fatty streaks in all of the hormone
      treatment groups as compared with both the ovariectomized and sham-operated
      animals that received placebo pellets. CONCLUSION(S): There were no significant
      differences in lesion area in response to estrogen alone or to estrogen plus the
      different types and doses of progestins.

PMID- 15474087
TI  - SAPKgamma/JNK1 and SAPKalpha/JNK2 mRNA transcripts are expressed in early
      gestation human placenta and mouse eggs, preimplantation embryos, and trophoblast
      stem cells.
AB  - OBJECTIVE: To test early-gestation human placenta, a human trophoblast cell line,
      mouse eggs, preimplantation embryos, and a mouse trophoblast cell line for the
      expression of mRNA transcripts for stress-activated protein kinase/c-Jun N
      terminal kinase (SAPKgamma/JNK1, SAPKalpha/JNK2, and SAPKbeta/JNK3). DESIGN:
      Whole RNA was isolated from the tissue sources listed above and control tissues,
      and reverse transcription-polymerase chain reaction (RT-PCR) was performed to
      assay for the qualitative and semiquantitative presence of SAPKgamma/JNK1,
      SAPKalpha/JNK2, and SAPKbeta/JNK3. SETTING: None. PATIENT(S): None.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The presence and magnitude of
      amplimer amounts in gels or gene hybridization on Affymetrix cDNA arrays of RT
      PCR products of reactions for SAPKgamma/JNK1, SAPKalpha/JNK2, and SAPKbeta/JNK3.
      RESULT(S): SAPKgamma/JNK1 and SAPKalpha/JNK2 mRNA transcripts are present in
      early-gestation human placenta, a human trophoblast cell line, mouse eggs,
      preimplantation embryos, and a mouse trophoblast cell line at levels similar to
      positive control levels. SAPKalpha/JNK2 is expressed at the highest level of the
      three transcripts in the family. SAPKbeta/JNK3 is present at levels that are
      1/100-1/1,000 those of the positive control and in some cases at the apparent
      level of the negative control (previously measured by the less-sensitive Northern
      blot analysis). Analysis with an Affymetrix cDNA array suggested that
      SAPKalpha/JNK2 and 38 kDa mitogen-activated protein kinase had the highest mRNA
      expression measured for each of three family members. CONCLUSION(S): Mitotic
      placental trophoblast cell lines and primary conceptus/embryo samples containing
      early placental trophoblasts express SAPKalpha/JNK2 at higher levels than
      SAPKgamma/JNK1, but not (only low background levels of) SAPKbeta/JNK3 mRNA
      transcripts. This suggests that SAPKgamma/JNK1 and SAPKalpha/JNK2 may be
      important mediators of stress-induced responses in early implanting conceptuses
      that could mediate embryo loss.

PMID- 15474088
TI  - Role of vascular endothelial growth factor receptor 1 in basal adhesion formation
      and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after
      laparoscopic surgery in mice.
AB  - OBJECTIVE: To evaluate the role of vascular endothelial growth factor receptor-1
      (VEGFR-1) in adhesion formation after laparoscopic surgery. DESIGN: Prospective,
      randomized study. SETTING: Academic research center. ANIMAL(S): Forty female
      Swiss mice. INTERVENTION(S): Adhesions were induced by standardized lesions
      during laparoscopy. The CO2 pneumoperitoneum was maintained for the minimum time
      needed to perform the lesions (10 minutes) or for a longer period (60 minutes) to
      evaluate basal adhesions and pneumoperitoneum-enhanced adhesions, respectively.
      Mice were treated either with IgG or with antibodies against VEGFR-1. MAIN
      OUTCOME MEASUREMENT(S): Adhesions were quantitatively and qualitatively scored
      after 7 days during laparotomy. RESULT(S): In IgG-treated mice, 60 minutes of CO2
      pneumoperitoneum increased basal adhesions. In VEGFR-1 antibody-treated mice,
      basal adhesions were similar to the control group and 60 minutes of CO2
      pneumoperitoneum did not increase adhesions. Therefore, in these mice,
      pneumoperitoneum-enhanced adhesions were lower than in IgG-treated mice.
      CONCLUSION(S): The data confirm that CO2 pneumoperitoneum is a cofactor in
      adhesion formation and demonstrate that VEGFR-1 plays a role in pneumoperitoneum
      enhanced adhesions, which is consistent with a role of placental growth factor,
      VEGF-A, and VEGF-B in pneumoperitoneum-enhanced adhesions. These observations
      give new insight into the pathogenesis of adhesion formation.

PMID- 15474089
TI  - Activation of soluble guanylyl cyclase inhibits estradiol production and cyclic
      AMP accumulation from cultured rat granulosa cells.
AB  - OBJECTIVE: To demonstrate the expression of soluble guanylyl cyclase (sGC) alpha
      and beta subunits in rat granulosa cells and determine the effects sGC activation
      on levels of cyclic GMP (cGMP), E2, and cAMP. DESIGN: Basic research study.
      SETTING: University research laboratory. ANIMAL(S): Estrogen-treated immature
      Sprague-Dawley female rats from which primary cell culture of granulosa cells was
      obtained. INTERVENTION(S): Functionally immature rat granulosa cells were
      incubated for 48 hours with media alone, FSH, or FSH plus YC-1, a specific
      activator of sGC. MAIN OUTCOME MEASURE(S): Expression of sGC alpha and beta
      subunits was determined by immunoblot analysis. Media concentrations of E2, cAMP,
      and cGMP were measured by radioimmunoassays. RESULT(S): Immunoblot analysis of
      granulosa cells revealed the expression of sGC alpha and beta subunits. While
      cGMP accumulation was low in cells incubated with media alone or with FSH,
      cotreatment with FSH plus YC-1 increased cGMP levels approximately five-fold.
      Incubation of cells with FSH stimulated E2 production in a dose-dependent manner.
      However, cotreatment of cells with FSH plus YC-1 significantly decreased E2
      concentrations at all doses of FSH tested. Similarly, while FSH increased cAMP
      accumulation from granulosa cells, cotreatment with YC-1 markedly inhibited FSH
      stimulated cAMP levels. CONCLUSION(S): These findings demonstrate the expression
      of sGC subunits in rat granulosa cells and indicate that activation of sGC
      increases cGMP levels, which are associated with inhibition of FSH-stimulated E2
      production and cAMP accumulation.

PMID- 15474090
TI  - Cyclic changes in the mammary gland of cynomolgus macaques.
AB  - OBJECTIVE: To evaluate the influence of hormonal changes during the menstrual
      cycle on the mammary gland of female cynomolgus monkeys. DESIGN: Paired breast
      biopsy samples were obtained during the follicular and luteal phases of the
      cycle. Cycle characteristics were assessed by vaginal bleeding, serum hormones,
      vaginal cytology, and uterine ultrasound. The mammary gland was assessed by
      histology and immunohistochemistry for Ki67, estrogen receptors (ER) alpha and
      beta, progesterone receptors (PR), and cleaved caspase 3 (CPP32). SETTING:
      Nonhuman primate study in an academic research environment. ANIMAL(S): Fifty-two
      adult, female, feral cynomolgus macaques (Macaca fascicularis), aged 8 to 20
      years, obtained from the breeding colony of the Institut Pertanian Bogor (Bogor,
      Indonesia). INTERVENTION(S): None MAIN OUTCOME MEASURE(S): Breast
      histomorphometry, immunohistochemical detection of Ki67, ERs, PR, and CPP32 in
      breast epithelial cells, and correlation with serum estradiol and progesterone.
      RESULT(S): Serum hormones, vaginal cytology and bleeding patterns were indicative
      of cycle stage. For lobules, Ki67 expression was higher in the follicular than in
      the luteal phase. In ducts, Ki67 expression was higher in the luteal than in the
      follicular phase. Estrogen receptors did not change across the cycle, but ER beta
      was more abundant. Ductal PR decreased in the luteal phase. Lobular CPP32 was
      higher during the luteal phase. Correlations of serum estradiol to outcomes
      varied by cycle stage. CONCLUSION(S): These data indicate important regulatory
      differences in the balance of proliferation and apoptosis in epithelial
      subpopulations within the breast across the menstrual cycle, indicating different
      regulatory roles for ER alpha and beta.

PMID- 15474091
TI  - Oxidative stress indices in follicular fluid as measured by the
      thermochemiluminescence assay correlate with outcome parameters in in vitro
      fertilization.
AB  - OBJECTIVE: To evaluate oxidative stress indices in follicular fluid (FF) by a
      novel thermochemiluminescence (TCL) assay and investigate the correlation between
      TCL and i.v.f. cycle parameters. DESIGN: Prospective, cross-sectional study.
      SETTING: I.v.f. Unit of an Obstetrics and Gynecology Department in a university
      affiliated hospital. PATIENT(S): One hundred eighty-nine women undergoing
      consecutive i.v.f. treatment cycles during 2001. INTERVENTION(S): After oocyte
      retrieval, pooled FF was centrifuged and the supernatant was tested in the TCL
      assay. MAIN OUTCOME MEASURE(S): Maximal serum E2 levels, number of gonadotropin
      ampoules, retrieved oocytes, mature oocytes, fertilization and cleavage rates,
      number of available embryos and cryopreserved embryos, and clinical pregnancy
      rates and correlation with TCL indices. RESULT(S): The TCL curve slope of FF
      positively correlated with maximal serum E2 levels, number of mature oocytes, and
      number of cleaved embryos and was inversely correlated with the women's ages and
      the number of gonadotropin ampoules. Follicular fluid TCL amplitude at 50 seconds
      ranged from 294 to 711 cps, but all pregnancies (n = 50; 28.1%) occurred within
      the range of 347-569 cps. With 385 and 569 cps as cutoff levels for the
      occurrence of pregnancy, the negative predictive value beyond this range was 96%
      and the positive predictive value within this range was 32%. CONCLUSION(S): The
      TCL results may reflect the age-related increase in free radical activity and is
      associated with parameters of ovarian responsiveness and IVF outcome. A certain
      threshold of oxidative stress may be required for the occurrence of conception in
      i.v.f. TCL is a potential tool to evaluate, treat, and monitor antioxidant
      therapy in i.v.f. treatments.

PMID- 15474092
TI  - Tumor necrosis factor-alpha-308 promoter and p53 codon 72 gene polymorphisms in
      women with leiomyomas.
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine,
      plays an important role in the process of autoimmune diseases. p53 is related to
      the regulation of cell growth and prevention of carcinogenesis. We propose to
      investigate whether gene polymorphisms for TNF-alpha-308 promoter and p53 could
      be used as markers of susceptibility in leiomyomas. DESIGN: Prospective basic
      study. SETTING: Departments of gynecology and genetics in a medical center.
      PATIENT(S): Group 1: leiomyoma (n = 159); group 2: non-leiomyoma (n = 131).
      INTERVENTION(S): Genomic DNA was obtained from peripheral leukocyte. The TNF
      alpha and p53 gene polymorphisms were amplified by polymerase chain reaction
      (PCR), enzyme restriction, and electrophoresis. MAIN OUTCOME MEASURE(S): Two gene
      polymorphisms were identified: [1] the A (cuttable)/G (uncuttable) polymorphisms
      of the TNF-alpha gene on chromosome 6p21.3; [2] A (cuttable)/P (uncuttable)
      polymorphisms of the p53 gene on chromosome 17p. Genotype and allelic frequencies
      in both groups were compared. RESULT(S): Genotype distribution and allele
      frequency of TNF-alpha gene polymorphism in both groups were significantly
      different. Proportions of A homozygote/heterozygote/G homozygote for TNF-alpha in
      both groups were: (group 1) 61%/34.6%/4.4% and (group 2) 81.7%/14.5%/3.8%.
      Proportions of allele A/G for TNF-alpha in both groups were: (group 1)
      78.3%/21.7% and (group 2) 88.9%/11.1%. Distributions of p53 polymorphisms in both
      groups were not different. The proportions of A homozygotes/heterozygotes/P
      homozygotes for p53 were (group 1) 32.7%/42.1%/25.2% and (group 2)
      28.2%/48.9%/22.9%. CONCLUSION(S): G homozygote and G allele for TNF-alpha
      promoter are related to a higher risk of leiomyomas. The p53 codon 72 gene
      polymorphism is not associated with the susceptibility of leiomyomas.

PMID- 15474093
TI  - Comparative ultrastructure of collagen fibrils in uterine leiomyomas and normal
      myometrium.
AB  - OBJECTIVE: To examine the ultrastructural characteristics of extracellular matrix
      and mature collagen fibrils in uterine leiomyomas and compare them with those in
      adjacent normal myometrium. DESIGN: Analysis of paired leiomyoma-myometrium in
      surgical specimens. SETTING: Research center and tertiary care center.
      SUBJECT(S): Women undergoing medically indicated hysterectomy for symptomatic
      uterine leiomyomas. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Appearance
      and spatial orientation of the collagen fibrils in leiomyomas compared with
      myometrium. RESULT(S): Observation of specimens at x 12,500 magnification
      indicated that collagen fibrils were more abundant, loosely packed, and arrayed
      in a nonparallel manner in leiomyomas compared with myometrium. Random areas were
      examined at x 6,500 to x 64,000 magnification and revealed collagen fibrils of
      equal diameter in both leiomyomas and myometrium. However, an ordered and regular
      barbed appearance was present in collagen fibrils from myometrium but was lacking
      in leiomyomas. CONCLUSION(S): Leiomyomas contain an abnormal collagen fibril
      structure and orientation, which suggests that the well-regulated fibril
      formation in myometrium is altered in leiomyomas. Alterations in collagen genes
      may play a role in the pathogenesis of leiomyomas.

PMID- 15474094
TI  - Differential expression of alpha smooth muscle cell actin in human fibroblasts
      isolated from intraperitoneal adhesions and normal peritoneal tissues.
AB  - OBJECTIVE: To determine whether alpha smooth muscle cell actin (alphaSMCA) is
      expressed in human fibroblasts isolated from normal peritoneal and adhesion
      tissues. DESIGN: Prospective, experimental study. SETTING: University medical
      center. PATIENT(S): Five patients undergoing laparotomy for adhesiolysis for
      pelvic pain. INTERVENTION(S): Primary culture of fibroblasts from both peritoneum
      and adhesion tissues. MAIN OUTCOME MEASURE(S): Immunohistochemistry techniques
      were used to determine whether alphaSMCA was present in normal peritoneal and
      adhesion fibroblasts from the same patients. Cultured fibroblasts from all
      tissues were also fixed on slides and stained with alphaSMCA monoclonal antibody
      labeled with immunofluorescence. RESULT(S): Alpha SMCA protein was present in
      very low levels in the cytoplasm of normal peritoneal fibroblasts from all five
      subjects, as compared with high levels present in adhesion fibroblasts from the
      same patients. CONCLUSION(S): Adhesion fibroblasts develop a specific phenotype,
      an adhesion phenotype, which in part is characterized by the over-expression of
      alphaSMCA. The over-expression of alphaSMCA in adhesion fibroblasts indicates a
      possible response to peritoneal injury. Regulation of alphaSMCA might alter
      peritoneal healing and might provide the opportunity to reduce postoperative
      adhesion development.

PMID- 15474095
TI  - Mevastatin inhibits ovarian theca-interstitial cell proliferation and
      steroidogenesis.
AB  - OBJECTIVE: Statins reduce cardiovascular risks by improving hypercholesterolemia,
      reducing vascular smooth muscle proliferation, and ameliorating inflammation.
      Polycystic ovary syndrome (PCOS) is associated with increased cardiovascular
      risks and is characterized by ovarian theca-interstitial hyperplasia and
      hyperandrogenism. This study tested the hypothesis that mevastatin limits theca
      interstitial proliferation and decreases steroidogenesis. DESIGN: In vitro study.
      SETTING: Academic laboratory. PATIENT(S): None. INTERVENTION(S): Effects of
      mevastatin on cultured theca-interstitial cells. MAIN OUTCOME MEASURE(S):
      Proliferation was evaluated by determination of DNA synthesis using thymidine
      incorporation assay and by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium
      bromide (MTT) assay. Production of P and T was determined by specific
      radioimmunoassays. RESULT(S): Mevastatin induced a profound concentration
      dependent inhibition of DNA synthesis. At the highest concentration (30 microM),
      mevastatin inhibited DNA synthesis by 92%. Similarly, in the MTT proliferation
      assay, mevastatin induced a concentration-dependent decrease in cell number.
      Mevastatin decreased production of P (by up to 49%) and T (by up to 52%); these
      effects remained significant when the effect on cell culture protein content was
      accounted for. CONCLUSION(S): Mevastatin inhibits proliferation of theca
      interstitial cells; it also inhibits P and T production independently of the
      effects on cell growth. These findings provide a foundation for studies
      evaluating statins as potential therapeutic agents in the treatment of ovarian
      mesenchymal hyperplasia and hyperandrogenism characteristic of PCOS.

PMID- 15474096
TI  - Role of nitric oxide in apoptosis of human peritoneal and adhesion fibroblasts
      after hypoxia.
AB  - OBJECTIVE: To study the modulation of the inducible nitric oxide synthase/nitric
      oxide (iNOS/NO) expression system in fibroblasts isolated from human peritoneum
      and adhesion tissues by hypoxia. DESIGN: Prospective experimental study. SETTING:
      University medical center. PATIENT(S): Cultures of fibroblasts from both
      peritoneum and adhesion tissues of five patients. INTERVENTION(S): Hypoxia
      treatment of the primary cultured fibroblasts. MAIN OUTCOME MEASURE(S): We used
      Western and Northern blots to determine whether iNOS mRNA and its protein were
      present in peritoneal and adhesion fibroblasts and whether this expression is
      modulated by hypoxia. Multiplex reverse transcription polymerase chain reaction
      (RT-PCR) technique was used to quantify type I collagen mRNA in response to NG
      nitro-L-arginine methyl ester (L-NAME). A terminal deoxynucleotidyl transferase
      mediated dUTP nick-end-labeling (TUNEL) assay was used to quantify apoptosis in
      response to NO donor S-nitro-N-acetyl-penicillamine (SNAP) treatment. A Griess
      assay was used to measure NO levels. RESULT(S): Peritoneal fibroblasts have
      significantly higher NO levels than adhesion fibroblasts. Hypoxia decreased NO in
      peritoneal fibroblasts to levels observed for adhesion fibroblasts. In addition,
      hypoxia increased both mRNA and protein levels of the iNOS gene in peritoneal and
      adhesion fibroblasts. Augmentation of NO by SNAP treatment increased apoptosis in
      adhesion fibroblasts. In contrast, SNAP had no effect on apoptosis of peritoneal
      fibroblasts. Inhibition of NO by L-NAME treatment increased type I collagen mRNA
      levels in peritoneal fibroblasts. CONCLUSION(S): Our findings confirm that
      adhesion fibroblasts produce less NO than normal peritoneal fibroblasts; NO may
      be the mechanism responsible for the creation and persistence of the adhesion
      phenotype.

PMID- 15474097
TI  - Production of macrophage inflammatory protein-3alpha in human follicular fluid
      and cultured granulosa cells.
AB  - OBJECTIVE: To investigate the role of macrophage inflammatory protein (MIP)
      3alpha in human ovulation. DESIGN: Study of the levels of MIP-3alpha in serum and
      follicular fluid. The effects of interleukin (IL)-1alpha, IL-1 receptor
      antagonist (RA), and tumor necrosis factor (TNF)-alpha on the secretion of MIP
      3alpha by primary cultured granulosa-lutein cells and an immortalized granulosa
      cell line (GC1a) were investigated. SETTING: Research laboratory at a university
      medical school. PATIENT(S): Forty-six patients with sterility undergoing in vitro
      fertilization and embryo transfer (i.v.f.-ET). INTERVENTION(S): Follicular fluid
      was obtained from study participants, and granulosa-lutein cells and GC1a were
      incubated with IL-1alpha, IL-1RA, or TNF-alpha for 4 to 32 hours. MAIN OUTCOME
      MEASURE(S): The concentration of MIP-3alpha in human follicular fluid was
      measured and correlated with oocyte maturation. We also cultured granulosa cells
      and examined the regulation of MIP-3alpha production. The concentrations of MIP
      3alpha in the serum, follicular fluid, and culture medium were measured using
      enzyme-linked immunoabsorbent assay. RESULT(S): Concentrations of MIP-3alpha were
      significantly higher in the follicular fluid, but it was not detected in the
      serum. Concentrations of MIP-3alpha were statistically significantly higher in
      the follicular fluid containing mature oocytes than in follicular fluid
      containing immature oocytes. The production of MIP-3alpha was markedly increased
      over the basal level after treatment with IL-1alpha and TNF-alpha in a dose
      dependent manner. The stimulatory effect of IL-1alpha was inhibited by IL-1RA.
      CONCLUSION(S): Our data suggest that MIP-3alpha was present in follicular fluid
      and correlated with oocyte maturation, and was regulated by IL-1alpha and TNF
      alpha. Thus, MIP-3alpha may play an important role in the human preovulatory
      process.

PMID- 15474098
TI  - 17beta-estradiol and progesterone do not influence the production of cytokines
      from lipopolysaccharide-stimulated monocytes in humans.
AB  - OBJECTIVE: To test whether 17beta-estradiol or progesterone influence the
      cytokine productive capacity of lipopolysaccharide (LPS)-stimulated monocytes in
      humans. DESIGN: Prospective study. SETTING: Academic research institution.
      PATIENT(S): Seven women in the luteal phase of a normal ovarian cycle, 13 oral
      contraceptive users, 10 men, and 10 postmenopausal women. INTERVENTION(S): Blood
      samples collected from women in the luteal phase and from oral contraceptive
      users were used to study the in vivo effect of 17beta-estradiol and progesterone
      on monocyte cytokine production. Blood samples collected from men and
      postmenopausal women were used for in vitro incubation with 17beta-estradiol and
      progesterone. MAIN OUTCOME MEASURE(S): The percentage of monocytes producing
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) after in
      vitro LPS-stimulation was determined. RESULT(S): No in vivo relation in the
      productive capacities of LPS-stimulated monocytes in the luteal phase of the
      ovarian cycle was found between progesterone and TNF-alpha or IL-1beta; or
      between 17beta-estradiol and TNF-alpha or IL-1beta. Moreover, the production of
      TNF-alpha and IL-1beta by LPS-stimulated monocytes did not vary between periods
      of oral contraceptive use and nonuse. The production of TNF-alpha and IL-1beta by
      LPS-stimulated monocytes in the blood of men and postmenopausal women in vitro
      was not influenced by incubation with different concentrations of 17beta
      estradiol or progesterone. CONCLUSION(S): We could not find evidence for a causal
      relationship between 17beta-estradiol or progesterone and TNF-alpha- or IL-1beta
      production. We conclude that 17beta-estradiol and progesterone do not influence
      the cytokine-production capacity of LPS-stimulated monocytes in humans.

PMID- 15474099
TI  - Human decidual production of hepatocyte-growth factor is not influenced by
      trophoblastic invasion in vivo.
AB  - OBJECTIVE: To evaluate and compare production of hepatocyte growth factor (HGF)
      from human first-trimester implantation-site decidua (decidua basalis) and
      nonimplantation site decidua (decidua parietalis), and hence to determine whether
      human trophoblast invasion in vivo is associated with increased decidual HGF
      production. DESIGN: Controlled prospective study. SETTING: University hospital
      based study. PATIENT(S): Ten women undergoing first-trimester termination of
      singleton pregnancy for psychosocial reasons without preexisting medical or
      gynecologic diseases. INTERVENTION(S): Decidual samples surgically excised and
      processed for paraffin-embedded immunohistochemistry and for reverse
      transcription-polymerase chain reaction (RT-PCR) studies. MAIN OUTCOME
      MEASURE(S): Protein and mRNA production in decidua basalis and decidua parietalis
      by immunohistochemistry and RT-PCR, respectively. RESULT(S): No statistically
      significant difference was found between decidua basalis and decidua parietalis
      in HGF protein or mRNA production. Immunohistochemical analysis (n = 9) showed a
      mean score of 3.28 +/- 2.37 for decidua basalis and 3.61 +/- 2.66 for decidua
      parietalis. Semiquantitative analysis of HGF mRNA expression between the two
      sites showed no statistically significant difference (n = 10) CONCLUSION(S):
      Human decidual production of HGF is not influenced by trophoblastic invasion in
      vivo.

PMID- 15474100
TI  - Detection of implantation-related cytokines in cervicovaginal secretions and
      peripheral blood of fertile women during ovulatory menstrual cycles.
AB  - OBJECTIVE: To determine whether cytokines implicated in uterine receptivity are
      detectable in cervicovaginal secretions and/or serum of fertile women, and
      whether their concentrations undergo hormonal regulation during the menstrual
      cycle. DESIGN: Prospective, observational study. SETTING: Academic medical
      center. PATIENT(S): Six fertile volunteers studied over two menstrual cycles.
      INTERVENTION(S): Cervicovaginal lavages (CVLs) and peripheral blood specimens
      were obtained during the menstrual, proliferative, periovulatory, and
      midsecretory phases of the cycle. Endometrial biopsies were obtained during the
      midsecretory phase. MAIN OUTCOME MEASURE(S): Concentrations of leukemia
      inhibitory factor (LIF), macrophage-colony stimulating factor (M-CSF),
      interleukin-1beta (IL-1beta), transforming growth factor-beta1 (TGF-beta1), TGF
      beta2, and epidermal growth factor (EGF) in CVL and peripheral blood of fertile
      women; endometrial cytokine messenger (m)RNA levels in midsecretory phase; and
      serum E(2) and P levels throughout the menstrual cycle. RESULT(S): Macrophage
      colony stimulating factor and EGF were detectable in all CVL samples. Macrophage
      colony stimulating factor concentrations were positively correlated with serum E2
      levels and the E2/P ratio. Whereas EGF concentrations in serum and CVL samples
      remained constant throughout the menstrual cycle, individual concentrations
      during the secretory phase of the menstrual cycle were positively correlated with
      endometrial EGF mRNA levels. Interleukin-1beta, TGF-beta1, and TGF-beta2 were
      detected in most CVL samples. Interleukin-1beta concentrations in CVL were
      significantly higher at menses than at the periovulatory stage of the menstrual
      cycle; TGF-beta2 levels were higher at menses than at the periovulatory and
      secretory stages. Leukemia inhibitory factor was undetectable in CVL except at
      menses. In serum, TGF-beta1, TGF-beta2, M-CSF, and EGF were detectable, but there
      was no menstrual cycle effect. There were no correlations between cytokine levels
      in CVL and serum. CONCLUSION(S): This study demonstrates that several endometrial
      cytokines that have been implicated in uterine receptivity are detectable in
      cervicovaginal secretions and peripheral blood of reproductive-aged women, and it
      provides normal concentration ranges of these cytokines in CVL and serum of
      fertile women at four stages of the menstrual cycle. Macrophage-colony
      stimulating factor and EGF warrant further study in CVLs of fertile and infertile
      women to determine their predictive value as minimally invasive markers of
      uterine receptivity.

PMID- 15474101
TI  - Expression of stem cell factor and its receptor in human fetal and adult ovaries.
AB  - OBJECTIVE: To investigate the immunocytochemical expression and presence of mRNA
      transcripts of stem cell factor (SCF) and its receptor (SCF-R) in ovaries from
      human adults and fetuses. DESIGN: Immunocytochemical and reverse transcription
      polymerase chain reaction (RT-PCR) study. SETTING: Major tertiary care and
      referral academic centers. PATIENT(S): Seven women and girls undergoing
      laparoscopic ovarian biopsy and 13 women undergoing second and third trimester
      pregnancy terminations. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Microscopic morphometric analysis, immunocytochemistry for SCF and SCF-R, and RT
      PCR analyses. RESULT(S): There was strong to moderate immunocytochemical staining
      for SCF and its receptor in oocytes from primordial stages onward, but not in
      granulosa cells, in both fetal and adult ovarian samples. Transcripts of SCF and
      SCF-R RNA were detected by RT-PCR analyses for SCF and SCF-R. CONCLUSION(S): The
      expression of SCF and its receptor in ovarian tissue from fetuses and women
      suggests a possible role of SCF in growth initiation of human primordial
      follicles.

PMID- 15474102
TI  - Estrogen receptor alpha and beta expression in uterine leiomyomas from
      premenopausal women.
AB  - OBJECTIVE: To measure messenger RNA levels of estrogen receptor (ER) alpha and
      beta in uterine leiomyomas, normal myometrium, and endometrium. DESIGN:
      Prospective study. SETTING: University hospital. PATIENT(S): Seventeen
      premenopausal women who underwent surgery due to symptomatic uterine leiomyomas.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Quantitative RT-PCR was used for
      evaluation of ERalpha and ERbeta expression. Results were normalized to total
      cellular DNA. RESULT(S): Expression of ERalpha and ERbeta did not differ between
      leiomyomas and myometrium; however, in both tissues, expression of ERalpha was
      significantly higher than that of ERbeta. Estrogen receptor-alpha expression in
      endometrium was lower than in leiomyomas and myometrium. In leiomyomas and
      endometrium, correlations between expression of ERalpha and ERbeta were found.
      CONCLUSION(S): Uterine leiomyomas, myometrium, and endometrium display distinct
      patterns of ER expression.

PMID- 15474104
TI  - Intratympanic corticosteroids for Meniere's disease and vertigo.
AB  - Hearing loss can be caused by acoustic trauma, aging, ototoxic medications, and
      various other causes. At the cellular level hearing loss seems to be mediated by
      reactive oxygen species and ultimately through the activation of apoptotic
      mechanisms. This article explains the cellular and molecular mechanisms of
      hearing loss and presents medications that could be used in the intratympanic
      treatment of hearing loss.

PMID- 15474105
TI  - Intratympanic treatment of hearing loss with novel and traditional agents.
AB  - As knowledge of the cellular and molecular pathophysiology behind otopathologies
      expands, the possibility exists of preventing sensorineural hearing loss and
      perhaps reversing the loss. Cellular and molecular mechanisms seem to be similar
      in hearing loss secondary to aging, drug ototoxicity, noise, or other mechanisms.
      A final common pathway may hinge upon apoptosis. It is likely that anti-apoptotic
      factors will increasingly be realized as an important intervention strategy for
      sensorineural hearing loss. Furthermore, it is also possible that mounting a
      staged attack at the various regions in the pathway leading to cellular damage
      using a combination of several protective substances such as steroids,
      antioxidants, neurotrophic factors, anti-apoptotic compounds, and mitochondrial
      enhancers may prevent hearing loss and even reverse it in some situations. This
      article has presented some of the molecular and cellular mechanisms for hearing
      loss and potential ways of treating them. In theory, the delivery of these
      medications to the inner ear transtympanically would decrease systemic side
      effects and be more target specific. Because most of the studies conducted to
      date have been animal studies, randomized, double-blind, placebo-controlled
      clinical trials would be necessary before the use of these therapies becomes
      common practice.

PMID- 15474107
TI  - The history of intratympanic drug therapy in otology.
AB  - The application of drugs through the eardrum and into the middle ear to treat
      various otologic disorders has recently gained wide-spread popularity. Despite
      the relatively recent interest in this technique, if one considers any
      application of medication into the middle ear as intratympanic therapy, the roots
      of this method can really be considered to date back to antiquity. This article
      presents the development of intratympanic drug therapy from early times through
      the nineteenth century.

PMID- 15474106
TI  - Intratympanic perfusion for the treatment of tinnitus.
AB  - Intratympanic treatment of tinnitus with corticosteroids or gentamicin should be
      considered as an option of treatment in selected tinnitus patients, alone or in
      combination with standard modalities of management such as tinnitus retraining
      therapy, masking, and hearing aid amplification. Review of the literature and the
      authors' experience suggest the following points regarding intratympanic
      treatment for tinnitus: 1. Lidocaine, although effective in decreasing tinnitus,
      has been largely abandoned because of its severe side-effect profile and need for
      inpatient administration. 2. Corticosteroids have been associated with few if any
      side effects. 3. The good results reported in the literature with intratympanic
      steroids for treating tinnitus of various causes should be viewed with
      caution,because most are retrospective and uncontrolled studies. 4. Some
      Meniere's disease patients with tinnitus may experience tinnitus improvement
      following intratympanic steroids. This treatment may be considered in such
      patients, especially for those with good hearing. 5. Gentamicin is effective in
      eliminating or reducing tinnitus in a significant number of patients with
      Meniere's disease and may be considered especially for those with nonserviceable
      hearing. 6. Further prospective, randomized, and controlled studies to evaluate
      the effect of intratympanic perfusion for the treatment of tinnitus are
      warranted.

PMID- 15474108
TI  - Silverstein MicroWick.
AB  - Using the MicroWick to deliver otic medication to the inner ear fluids isa new,
      unique, effective, safe, efficient, and inexpensive method to treat inner ear
      disease. This self-treatment method using otic medication represents a major
      breakthrough in the treatment of inner ear disease. It allows the otologist to
      treat inner ear disease much as the ophthalmologist treats eye disease using eye
      drops. In the future, new drugs and medications will likely be developed that
      will relieve vertigo attacks, improve certain types of sensorineural hearing
      loss, and reduce tinnitus. The MicroWick will be available for patients to self
      administer these medications to the inner ear through the round window membrane.

PMID- 15474109
TI  - The biology of intratympanic drug administration and pharmacodynamics of round
      window drug absorption.
AB  - The application of therapeutic agents to the round window holds great promise in
      the treatment of inner ear disease. The primary benefit of this route of
      administration is the ability to achieve high inner ear concentrations of drugs
      without systemic side effects. Recent research has elucidated the anatomy and
      physiology of the round window and provided important information on the inner
      ear pharmacokinetics and the pharmacodynamics of drugs administered
      intratympanically. Although amino-glycosides and steroids have been most
      thoroughly studied, many other classes of pharmaceuticals, including
      otoprotective agents, other antibiotics,and topical anesthetics, have therapeutic
      potential in the inner ear and will probably be the subject of future studies.
      The authors believe that direct delivery approaches other than through the round
      window, perhaps with slow or sustained release formulations, may hold the key to
      the future treatment of inner ear disorders.

PMID- 15474110
TI  - Sustained-release devices in inner ear medical therapy.
AB  - Inner ear medical therapy has been gaining increasing popularity during the last
      2 decades. Despite the increased use of this therapy,basic questions regarding
      this type of treatment have not been answered. The authors have used a variety of
      sustained-release devices in the laboratory to begin to answer some of these
      basic questions. This article discusses the results of this work and the
      application and use of sustained-release devices in patients.

PMID- 15474111
TI  - Intratympanic steroids for sensorineural hearing loss.
AB  - Corticosteroids are standard treatment for a number of inflammatory and immune
      mediated inner ear diseases. In recent years there has been growing interest in
      intratympanic administration of steroids as a means of achieving high inner ear
      drug concentration and low risk of systemic side effects. Idiopathic sudden
      sensorineural hearing loss seems to be the condition with the greatest potential
      for both study and clinical use of intratympanic steroid treatment. Despite
      promising preliminary observations, there re-main many unanswered questions about
      this treatment modality.

PMID- 15474112
TI  - Intratympanic gentamicin for the treatment of Meniere's disease and other forms
      of peripheral vertigo.
AB  - Titration therapy with intratympanic gentamicin offers class A or B control of
      vertigo in 87% (range, 75%-100%) of patients with unilateral Meniere's disease.
      The risk of additional hearing loss is about 21% (range,0-37%). Vertigo may
      recur, however, in nearly one third of patients over time. These recurrences can
      also be treated by intratympanic gentamicin with a similar risk of hearing loss.
      The salient effect of intratympanic gentamicin is probably the reduction of
      vestibular function through damage to hair cells, but a complete ablation of
      function does not seem to be necessary for vertigo control.

PMID- 15474113
TI  - Drug delivery to the inner ear using gene therapy.
AB  - The last 10 years have seen the development of numerous strategies for the
      delivery of genes to the inner ear. Besides being a useful research tool,gene
      therapy has significant promise as a potential clinical treatment. The human
      inner ear is easily accessible through either the round window or the stapes
      footplate. It is now possible to choose a variety of vectors to target a variety
      of different tissues. Modification of promoters yields different expression
      patterns as well as differences in degree of expression. Several animal studies
      have also demonstrated that expression of exogenous genes in the cochlea does not
      result in loss of hearing function. A variety of potential clinical applications
      are already evident from these early studies. Protective strategies such as
      prevention of neuronal degeneration and protection of auditory hair cells from
      oxidative stress are potential examples where gene therapy may be useful. As the
      understanding of gene therapy improves, investigators will be able to move toward
      targeted single-gene replacement to treat disorders such as connexin mutations
      and applying gene therapy to sensory cell replacement.

PMID- 15474114
TI  - Vioxx: an unequal partnership between safety and efficacy.

PMID- 15474115
TI  - A steppe towards a cooler world.

PMID- 15474116
TI  - Alcohol interventions in emergency medicine: referral makes a difference.

PMID- 15474117
TI  - Violence and mortality in West Darfur.

PMID- 15474118
TI  - A CRASH landing in severe head injury.

PMID- 15474119
TI  - Neonatal resuscitation on air: it is time to turn down the oxygen tanks
      [corrected].

PMID- 15474120
TI  - If only you hadn't, I would not have hit you: infant crying and abuse.

PMID- 15474121
TI  - India's response to the HIV epidemic.

PMID- 15474122
TI  - Targeting commercial sex-workers in Goa, India: time for a strategic rethink?

PMID- 15474123
TI  - Smart bombs versus blunderbusses: high-dose chemotherapy for breast cancer.

PMID- 15474124
TI  - Confounding variables and expression of myocardial NOS.

PMID- 15474125
TI  - Of birds and men: cardiologists' role in influenza pandemics.

PMID- 15474127
TI  - Primary open-angle glaucoma: pathophysiology and treatment.

PMID- 15474128
TI  - Schizophrenia.

PMID- 15474129
TI  - Schizophrenia.

PMID- 15474130
TI  - A difficult diagnosis.

PMID- 15474131
TI  - Schizophrenia.

PMID- 15474133
TI  - Violence and mortality in West Darfur, Sudan (2003-04): epidemiological evidence
      from four surveys.
AB  - BACKGROUND: Violence in Darfur, Sudan, has rendered more than one million people
      internally displaced. An epidemiological study of the effect of armed incursions
      on mortality in Darfur was needed to provide a basis for appropriate assistance
      to internally displaced people. METHODS: Between April and June, 2004, we did
      retrospective cluster surveys among 215?400 internally displaced people in four
      sites of West Darfur (Zalingei, Murnei, Niertiti, El Geneina). Mortality recall
      periods covered both the pre-displacement and post-displacement periods in
      Zalingei, Murnei, and Niertiti, but not in El Geneina. Heads of households
      provided dates, causes, and places of deaths, and described the family structure.
      FINDINGS: Before arrival at displacement sites, mortality rates (expressed as
      deaths per 10?000 per day), were 5.9 (95% CI 2.2-14.9) in Zalingei, 9.5 (6.4
      14.0) in Murnei, and 7.3 (3.2-15.7) in Niertiti. Violence caused 68-93% of these
      deaths. People who were killed were mostly adult men (relative risk 29.1-117.9
      compared with children younger than 15 years), but included women and children.
      Most households fled because of direct village attacks. In camps, mortality rates
      fell but remained above the emergency benchmark, with a peak of 5.6 in El
      Geneina. Violence persisted even after displacement. Age and sex pyramids of
      surviving populations were skewed, with a deficit in men. INTERPRETATION: This
      study, which was done in a difficult setting, provides epidemiological evidence
      of this conflict's effect on civilians, confirming the serious nature of the
      crisis, and reinforcing findings from other war contexts.

PMID- 15474134
TI  - Effect of intravenous corticosteroids on death within 14 days in 10008 adults
      with clinically significant head injury (MRC CRASH trial): randomised placebo
      controlled trial.
AB  - BACKGROUND: Corticosteroids have been used to treat head injuries for more than
      30 years. In 1997, findings of a systematic review suggested that these drugs
      reduce risk of death by 1-2%. The CRASH trial--a multicentre international
      collaboration--aimed to confirm or refute such an effect by recruiting 20000
      patients. In May, 2004, the data monitoring committee disclosed the unmasked
      results to the steering committee, which stopped recruitment. METHODS: 10008
      adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h
      of injury were randomly allocated 48 h infusion of corticosteroids
      (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of
      injury and death or disability at 6 months. Prespecified subgroup analyses were
      based on injury severity (GCS) at randomisation and on time from injury to
      randomisation. Analysis was by intention to treat. Effects on outcomes within 2
      weeks of randomisation are presented in this report. This study is registered as
      an International Standard Randomised Controlled Trial, number ISRCTN74459797.
      FINDINGS: Compared with placebo, the risk of death from all causes within 2 weeks
      was higher in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%]
      deaths; relative risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase
      in deaths due to corticosteroids did not differ by injury severity (p=0.22) or
      time since injury (p=0.05). INTERPRETATION: Our results show there is no
      reduction in mortality with methylprednisolone in the 2 weeks after head injury.
      The cause of the rise in risk of death within 2 weeks is unclear.

PMID- 15474135
TI  - Resuscitation of newborn infants with 100% oxygen or air: a systematic review and
      meta-analysis.
AB  - BACKGROUND: International consensus statements for resuscitation of newborn
      infants recommend provision of 100% oxygen with positive pressure if assisted
      ventilation is required. However, 100% oxygen exacerbates reperfusion injury in
      animals and reduces cerebral perfusion in newborn babies. We aimed to establish
      whether resuscitation with air decreased mortality or neurological disability in
      newborn infants compared with 100% oxygen. METHODS: We did a systematic review
      and meta-analysis of trials that compared resuscitation with air versus 100%
      oxygen, using the methods of the Cochrane Collaboration. We combined data for
      similar outcomes in the analysis where appropriate, using a fixed-effects model.
      FINDINGS: Five trials (two masked and three unmasked), consisting of 1302 newborn
      infants, fulfilled the inclusion criteria. Most babies were born at or near term
      in developing countries. In the three unmasked studies, infants resuscitated with
      room air who remained cyanotic and bradycardic were switched to 100% oxygen at 90
      s. The masked studies allowed crossover to the other gas during the first minutes
      of life. Although no individual trial showed a difference in mortality, the
      pooled analysis showed a significant benefit for infants resuscitated with air
      (relative risk 0.71 [95% CI 0.54 to 0.94], risk difference -0.05 [-0.08 to 
      0.01]). The effect on long-term development could not be reliably determined
      because of methodological limitations in the one study that followed up infants
      beyond 12 months of age. INTERPRETATION: For term and near-term infants, we can
      reasonably conclude that air should be used initially, with oxygen as backup if
      initial resuscitation fails. The effect of intermediate concentrations of oxygen
      at resuscitation needs to be investigated. Future trials should include and
      stratify for premature infants.

PMID- 15474136
TI  - Screening and referral for brief intervention of alcohol-misusing patients in an
      emergency department: a pragmatic randomised controlled trial.
AB  - BACKGROUND: Alcohol misuse is highly prevalent among people attending emergency
      departments, but the effect of intervention by staff working in these departments
      is unclear. We investigated the effect of screening and referral of patients
      found to be misusing alcohol while attending an emergency department. METHODS: We
      undertook a single-blind pragmatic randomised controlled trial. Patients received
      either an information leaflet or an information leaflet plus an appointment with
      an alcohol health worker. Outcome data were collected by patient interview and
      examination of hospital records at 6 and 12 months. FINDINGS: 599 patients were
      randomised over a 12-month period. At 6 months, those referred to an alcohol
      health worker were consuming a mean of 59.7 units of alcohol per week compared
      with 83.1 units in the control group (t -2.4, p=0.02). At 12 months those
      referred were drinking 57.2 units per week compared with 70.8 in controls (t 
      1.7, p=0.09). Those referred to the alcohol health worker had a mean of 0.5 fewer
      visits to the emergency department over the following 12 months (1.2 compared
      with 1.7, t -2.0, p=0.046). Differences in quality of life were not found.
      INTERPRETATION: Opportunistic identification and referral for alcohol misuse in
      an emergency department is feasible, associated with lower levels of alcohol
      consumption over the following 6 months, and reduces reattendance at the
      department. Short-term reductions in alcohol consumption associated with referral
      for brief intervention for alcohol misuse benefit patients and reduce demand for
      accident and emergency department services.

PMID- 15474137
TI  - Infant crying and abuse.
AB  - Child abuse and neglect are important causes of child morbidity and death. We
      assessed potentially detrimental parental actions induced by infant crying in
      3259 infants aged 1-6 months, in the Netherlands. In infants aged 6 months, 5.6%
      (95% CI 4.2-7.0) of parents reported having smothered, slapped, or shaken their
      baby at least once because of its crying. The risks of detrimental actions were
      highest for parents from non-industrialised countries, those with either no job
      or a job with short working hours, and those who judged their infant's crying to
      be excessive. Clinicians should be aware of the risks of abuse in children known
      to cry a lot and should target interventions at parents to help them cope with
      this crying.

PMID- 15474138
TI  - Sickle-cell disease.
AB  - With the global scope of sickle-cell disease, knowledge of the countless clinical
      presentations and treatment of this disorder need to be familiar to generalists,
      haematologists, internists, and paediatricians alike. Additionally, an underlying
      grasp of sickle-cell pathophysiology, which has rapidly accrued new knowledge in
      areas related to erythrocyte and extra-erythrocyte events, is crucial to an
      understanding of the complexity of this molecular disease with protean
      manifestations. We highlight studies from past decades related to such
      translational research as the use of hydroxyurea in treatment, as well as the
      therapeutic promise of red-cell ion-channel blockers, and antiadhesion and anti
      inflammatory therapy. The novel role of nitric oxide in sickle-cell
      pathophysiology and the range of its potential use in treatment are also
      reviewed. Understanding of disease as the result of a continuing interaction
      between basic scientists and clinical researchers is best exemplified by this
      entity.

PMID- 15474139
TI  - Sickle-cell disease: from Sierra Leone to southeast London.

PMID- 15474140
TI  - Attributable testing for abnormal prion protein, database linkage, and blood
      borne vCJD risks.
AB  - CONTEXT: National prospective collection of tonsillar tissue to be tested
      anonymously for abnormal lymphoreticular accumulation of prion protein (PrP) was
      approved to begin in the UK in 2004. The UK is not, however, testing autopsy
      specimens attributably for abnormal PrP (PrP(SC)) so that recipients at risk
      after a blood transfusion from, or exposed to surgical instruments from, a
      deceased carrier of variant Creutzfeldt-Jakob disease (vCJD) can be followed up
      to quantify transmission risks. In Switzerland, surveillance for subclinical vCJD
      includes unconsented testing in autopsies: consented testing of tonsillar tissue
      is potentially attributable to interrupt human-to-human vCJD transmission or
      treat it. STARTING POINT: The UK announced its first case of probable blood-borne
      vCJD transmission in December, 2003, and first detected a case of probable blood
      borne subclinical vCJD in July, 2004. To reduce the possible risk of onward
      transmission to other people, UK patients who had received vCJD-implicated plasma
      products are being contacted. They, and their general practitioner, are asked to
      inform anyone giving them medical, surgical, or dental treatment, and the
      patients must refrain from donating blood, tissues, or organs. WHERE NEXT?
      Prudent additional surveillance options for human PrP(SC)--particularly at
      autopsy or to sanction the release of quarantined operation sets pending
      effective decontamination--can be costed by reference to results for cattle and
      sheep. Some ethical or legal impediments to the UK's potentially-attributable
      testing for PrP(SC) may yet be rued.

PMID- 15474142
TI  - Health and politics in the 2003 war with Iraq: lessons learned.

PMID- 15474141
TI  - Health financing to promote access in low income settings-how much do we know?
AB  - In this article we outline research since 1995 on the impact of various financing
      strategies on access to health services or health outcomes in low income
      countries. The limited evidence available suggests, in general, that user fees
      deterred utilisation. Prepayment or insurance schemes offered potential for
      improving access, but are very limited in scope. Conditional cash payments showed
      promise for improving uptake of interventions, but could also create a perverse
      incentive. The largely African origin of the reports of user fees, and the
      evidence from Latin America on conditional cash transfers, demonstrate the
      importance of the context in which studies are done. There is a need for improved
      quality of research in this area. Larger scale, upfront funding for evaluation of
      health financing initiatives is necessary to ensure an evidence base that
      corresponds to the importance of this issue for achieving development goals.

PMID- 15474143
TI  - Subacute necrotising fasciitis.

PMID- 15474144
TI  - Statistical dissection of cytogenetic patterns in lung cancer reveals multiple
      modes of karyotypic evolution independent of histological classification.
AB  - Lung carcinomas are cytogenetically highly complex. In spite of this, patterns of
      recurrent chromosome aberrations have emerged. Apart from the frequent loss of
      3p, losses of 4q, 5q, 8p, 9p, 10q, 13q, and 17p are common and gains often
      include 1q, 3q, 5p, and 8q. In the present study, we retrieved all aberrant lung
      carcinoma karyotypes, in total 432 cases, from the Mitelman Database of
      Chromosome Aberrations in Cancer and identified the most frequent imbalances.
      Each case was then classified with respect to the presence or absence of these
      imbalances and the data were statistically analyzed by means of principal
      component analysis, multidimensional scaling, and hierarchical cluster analysis.
      The analyses suggest that lung cancer develops through three pathways, initiated
      by +7, 3p-, and +12, respectively, and that the 3p- pathway is dominated by
      losses and the +12 pathway by gains. Gain of chromosome 7 was shown to be both
      important in the 3p- pathway and also forming a group of tumors containing +7 and
      +20 (with few additional changes). The distribution of the number of imbalances
      per tumor indicated that the karyotypic evolution might pass through three
      different phases. Phase I is characterized by tumors with few changes and by well
      separated 3p- and +12 pathways. Phase II cases have an increased number of
      imbalances and exhibit less distinct 3p- and +12 pathways. Phase III tumors are
      polyploid and highly complex. No marked differences between the karyotypic
      profiles were found among morphologic subtypes, suggesting that lung cancer
      morphology is independent of the particular cytogenetic pathway operating in the
      tumor cells.

PMID- 15474145
TI  - Multiple abnormalities detected by dye reversal genomic microarrays in prostate
      cancer: a much greater sensitivity than conventional cytogenetics.
AB  - Prostate cancer remains the most common male malignancy in Western countries, yet
      limited information exists regarding genetic changes and clinical correlations.
      The advent of comparative genomic hybridization microarray (GM) technology has
      recently allowed for precise screening of DNAs for genetic copy number changes;
      this offers an advantage over previous techniques, including conventional
      cytogenetics. A problem with cytogenetic prostate cancer analysis has been the
      study of the appropriate cell types because this is a highly heterogeneous tumor.
      We have performed GM using the Spectral Genomics Inc. dye reversal platform on 20
      primary prostate tumors. These tumor samples were from frozen tissue collected
      over the last 10 years and multiple clinical parameters, including follow-up were
      collected on these patients; cytogenetic analysis was previously attempted on all
      patients. Eighty percent (16/20) of specimens showed copy number changes, 65% of
      which were losses and 35% were gains of genetic material. The most common changes
      observed were loss of an interstitial region of 2q (8 cases, 40%), followed by
      loss of interstitial 6q (6 cases, 30%), loss at 8p and 13q (5 cases each, 25%),
      gain at 3p and loss at 5q, 16q, and Xq (4 cases each, 20%), and gain at 8p (3
      cases, 15%). There was evidence of correlation of loss at 5q with a positive node
      status. Cytogenetic studies on these same patients only detected clonal changes
      in 40% (8/20) specimens and did not detect the majority of abnormalities seen by
      the GM technique. We propose this technology for the evaluation of prostate and
      other heterogeneous cancers as a rapid and efficient way to detect genetic copy
      number changes.

PMID- 15474146
TI  - Evidence for gains at 15q and 20q in brain metastases of prostate cancer.
AB  - Many detailed genetic studies have been reported on prostate carcinogenesis. A
      major shortcoming of these studies, however, is the fact that most data have been
      gained from investigations that were performed at a single point of time during
      tumor development. Only little is known on the dynamic process of genetic changes
      during the course of the disease. We performed comparative genomic hybridization
      in two cases of prostate cancer brain metastases. Tissue samples from the primary
      tumors, the locally recurrent tumor in one case, and the brain metastases from
      both cases were available for analysis. The number of chromosome abnormalities
      was found to be increased in the metastases. This contrasts to a remarkably
      stable chromosome composition of the primary tumor over several years, even in an
      androgen-depleted environment. When focusing on these changes, which either
      emerged as new common aberrations in both brain metastases, or which were
      commonly present in the primary and metastatic tumors, we were able to delineate
      five chromosomal sites that are assumed to be related to prostate cancer
      metastasis: 8q21 approximately q22, 8q24, 15q24 approximately q26, 20q12
      approximately q13.1, and Xq12 approximately q21. These findings provide new
      evidence for a putative role of genes at 15q and 20q in the metastatic process of
      prostate cancer.

PMID- 15474147
TI  - Cytogenetic analysis of three variants of clival chordoma.
AB  - Chordoma is an uncommon malignant neoplasm derived from remnants of the embryonal
      notochord. The tumor arises in the sacrococcygeal region in most cases.
      Cytogenetic information on clival chordomas is scarce due to the low incidence of
      these tumors. In this study, we applied the G-banding and spectral karyotyping
      techniques to compare the karyotypes of three variants of clival chordoma:
      conventional, chondroid, and dedifferentiated. We describe a normal karyotype of
      a chondroid chordoma and a complex karyotype of a conventional chordoma involving
      chromosomes 1, 2, 3, 5, 8, 9, 11, 15, 19, 20, and X. The cytogenetic analysis of
      the dedifferentiated chordoma showed a polyploid complex karyotype of 71-123
      chromosomes with double minutes that originated from chromosome 17.

PMID- 15474148
TI  - Positional gene expression analysis identifies 12q overexpression and
      amplification in a subset of neuroblastomas.
AB  - Neuroblastoma is a heterogeneous disease with variable clinical behaviors. Unique
      molecular features are associated with clinically relevant subgroups. We
      performed a comprehensive microarray gene expression analysis of 95
      neuroblastomas in an effort to define clinically important molecular subtypes. A
      subset of tumors overexpressed several contiguous genes located at 12q13
      approximately q15 and were studied further. By microarray, 5 of 95 neuroblastomas
      had overexpression of genes mapped to 12q13.1 approximately q15, suggesting an
      amplification event in this region. Positional expression mapping identified the
      narrowest region of overlap containing 21 genes, with 11 genes overexpressed in
      all five cases. Fluorescence in situ hybridization demonstrated 3 neuroblastomas
      with more than a 10-fold increase in 12q gene copies and 9 with 3- to 5-fold
      increases. Amplification and overexpression of genes at 12q13 approximately q15
      were observed in a small subset of neuroblastomas. Although amplification of 12q
      has been previously reported in neuroblastoma cell lines, this is the first
      demonstration in tumor samples, and it defines a distinct subset that has not
      been described previously. The expressed genes mapped closely to the complex
      amplicon reported in sarcomas, and they identify critical genes and pathways
      affected by 12q gene amplification.

PMID- 15474149
TI  - Interphase fluorescence in situ hybridization studies for the detection of 9q34
      deletions in chronic myelogenous leukemia: a practical approach to clinical
      diagnosis.
AB  - Chronic myelogenous leukemia (CML) is characterized by the Philadelphia
      chromosome (Ph) in more than 90% of cases. Recent studies using fluorescence in
      situ hybridization (FISH) have shown that in a subset of patients with CML,
      deletions of 9q34 involving the argininosuccinate synthetase region occur at the
      time of the Philadelphia translocation and are associated with a poor prognosis.
      We performed interphase FISH studies in 152 cases of CML using a dual-color, dual
      fusion probe system with a third probe directed at 9q34. Cytogenetic studies
      showed a simple (typical) Ph in 124/152 (82%), a cryptic Ph in 11/152 (7%), and a
      variant Ph chromosome with a complex translocation in 17/152 (11%) of cases.
      Interphase FISH studies showed single BCR/ABL fusion patterns in 48/152 (32%) of
      cases. Deletions of 9q34 were observed in 14% of all the cases and were present
      in 46% of cases with single BCR/ABL fusion pattern. All the 9q34 deletions
      occurred in cases with single BCR/ABL fusion signal. However, a single-fusion
      pattern is not specific for 9q34 deletions, and cases should be routinely
      screened for the presence of this prognostically significant abnormality by using
      a third probe directed specifically at 9q34.

PMID- 15474150
TI  - SBDS mutations and isochromosome 7q in a patient with Shwachman-Diamond syndrome:
      no predisposition to malignant transformation?
AB  - Shwachman-Diamond syndrome (SDS) is a genetic disorder characterized by
      pancreatic hypoplasia, recurrent infection, and bone marrow (BM) dysfunction. SDS
      patients have an increased frequency of myelodysplasia and leukemic
      transformation. Unspecific cytogenetic aberrations are a common finding in SDS.
      However, in a rising number of patients abnormalities of chromosome 7 have been
      reported, especially an i(7)(q10), which seems to be a non-random chromosome
      abnormality. Recently, the SDS gene has been mapped at locus 7q11 and
      subsequently cloned; recurrent mutations have been found. We report a case of SDS
      with an i(7)(q10) in the BM and two different mutations in the SBDS gene. At the
      age of 25 years, the patient suffers from mild aplastic anemia but does not show
      any clinical sign of myelodysplasia or leukemic transformation.

PMID- 15474151
TI  - Acquisition of i(8q) as an early event in malignant triton tumors.
AB  - Malignant triton tumors (MTT) are rare soft-tissue tumors characterized by a
      mixture of cells with nerve sheath and skeletal muscle differentiation. MTT is a
      histological variant of malignant peripheral nerve sheath tumors (MPNST). No
      characteristic cytogenetic anomaly has been detected in MPNST or MTT. In this
      paper, we report on the cytogenetic findings of an MTT from a 20-year old male
      with neurofibromatosis (NF1). The tumoral karyotype showed the modal number to be
      near-diploid and an abnormal karyotype with a Robertsonian translocation and 4
      markers: 49,XY,der(14;15)(q10;q10),+4mar. Spectral karyotyping revealed the
      karyotype: 49,XY, der(14;15)(q10;q10),+i(8)(q10)x4. Fluorescence in situ
      hybridization analysis of the tissue confirmed the presence of the additional
      i(8)(q10) in all tumoral cells. The sequence analysis of p53 revealed a
      polymorphism in exon 9, codon 329. The two alleles, TTC and TCC, codify for
      phenylalanine and serine, respectively. Our results indicate that all neoplastic
      cells have the same cytogenetic pattern, suggesting that both cell lines, which
      show nerve sheath and skeletal muscle differentiation, are derived from a unique
      stem cell. The acquired Robertsonian chromosomal recombinants might represent an
      event in the tumorigenesis of MTT, and the present data suggest that genes
      located on 8q can be involved in the development of MTT.

PMID- 15474152
TI  - Cytogenetic findings in phyllodes tumor and fibroadenomas of the breast.
AB  - The cytogenetic data on fibroadenomas and cystosarcoma phyllodes tumor of the
      breast, which are both biphasic breast tumors composed of epithelial and stromal
      components, are quite limited. In this study, we report on clonal chromosomal
      alterations in three fibroadenomas and one cystosarcoma phyllodes analyzed by GTG
      banding. The fibroadenomas presented mostly numerical abnormalities involving
      chromosomes 16, 18, and 21. One case presented a deletion on 17p. The
      cystosarcoma phyllodes presented numerous numerical abnormalities, mostly
      chromosome gains, and several marker chromosomes.

PMID- 15474153
TI  - Translocation (16;18)(p13;q21.3) in follicular lymphoma.
AB  - We describe a novel t(16;18)(p13;q21.3) in a male patient with follicular
      lymphoma. This unique chromosomal rearrangement has never been described in
      patients with follicular lymphoma. The breakpoint of 16p13 has several
      hematopoietic neoplasm-related genes such as MHC2TA, a master regulatory gene for
      HLA-D, and BCMA, tumor necrosis factor receptor super-family. The majority of
      follicular lymphomas have a rearrangement of the BCL2 gene, which is a
      pathogenetic factor in their development. The diagnostic and prognostic
      significance of this new translocation is yet to be determined.

PMID- 15474155
TI  - Acute megakaryoblastic leukemia with t(17;22)(q21;q13) and liver dysfunction.
AB  - The t(1;22)(p13;q13) is associated with acute megakaryoblastic leukemia (AMKL)
      seen mostly in young infants and known to have a poor prognosis. A 5-year-old
      child had prolonged prothrombin and partial thromboplastin times, low albumin,
      and decreased vitamin K-dependent coagulation factors and factor V activities at
      the time of AMKL diagnosis. All of these factors normalized following
      chemotherapy when remission was achieved. Cytogenetic analysis revealed a female
      karyotype with a balanced t(17;22)(q21;q13). Here, we present an AMKL pediatric
      case with a novel translocation and significant hepatocellular dysfunction that
      resolved with chemotherapy. The t(17;22) (q21;q13) may represent a variant of
      t(1;22)(p13;q13).

PMID- 15474154
TI  - Cytogenetic characterization of 5 pheochromocytomas.
AB  - Cytogenetic findings were identified in 5 adrenal pheochromocytomas (PCC),
      including two clinically malignant tumors. The 3 PCC with benign clinical
      behavior, including one associated with von Hippel-Lindau syndrome, displayed no
      clonal chromosomal aberrations. In contrast, both clinically malignant PCC were
      characterized by hypotriploid chromosome numbers and multiple numerical and
      structural changes involving various chromosomes. Overall, losses were observed
      more frequently than gains. Aberrations common to both malignant tumors included
      losses of chromosomes 4, 11p, 13q, 15q, 16p, 17p, and 18, and partial gains of
      chromosome 7. The present results indicate that the malignant phenotype in PCC is
      associated with considerable genetic instability, leading to highly aneuploid and
      aberrant karyotypes.

PMID- 15474156
TI  - Rhabdomyosarcoma in Nijmegen breakage syndrome: strong association with perianal
      primary site.
AB  - Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder resulting
      from mutations in the NBS1 gene, which encodes for the DNA double strand break
      repair protein nibrin. NBS is clinically characterized by microcephaly,
      dysmorphic features, immunodeficiency, and increased susceptibility to
      malignancy, mainly of lymphoid origin. Here, we describe a 7-year-old girl with
      NBS who is homozygous for the NBS1 698del4 mutation. She had been diagnosed with
      perianal rhabdomyosarcoma (RMS) and experienced severe toxicity from
      chemotherapy. RMS arising perianally is extremely uncommon but has been
      previously described in two cases with NBS. The strong association of perianal
      RMS with NBS should, therefore, be considered when confronted with a perianal
      RMS, as this carries important clinical implications in terms of potential need
      for therapy modification and follow up investigations. In addition, it suggests a
      role for the NBS1 gene and the nibrin dependent pathway in the pathogenesis of
      RMS, especially those arising perianally.

PMID- 15474157
TI  - Translocation (10;17)(q22;p13): a recurring translocation in clear cell sarcoma
      of kidney.
AB  - A clear cell sarcoma from the kidney of a 12-month-old male child manifested a
      balanced translocation, t(10;17)(q22;p13). This is the second report of this
      cytogenetic abnormality in renal clear cell sarcoma.

PMID- 15474158
TI  - Low frequency of NRAS and KRAS2 gene mutations in childhood myelodysplastic
      syndromes.
AB  - In children, myelodysplastic syndromes (MDS) represent less then 10% of all
      hematological malignancies; consequently, molecular genetic studies dealing with
      this group of patients are scarce. We have analyzed 35 archival bone marrow
      samples of children with MDS for the presence of mutations in the first and
      second exons of the NRAS and KRAS2 genes. Mutations were detected with single
      strand conformation polymorphism analysis in three patients. One patient harbored
      a mutation in the second exon of NRAS and two patients in the second exon of
      KRAS2. Sequencing was performed in two samples and novel mutations were found in
      both. One patient had a missense mutation in codon 45 of NRAS; the other had a
      silent mutation in codon 53 and a missense mutation in codon 55 of KRAS2.

PMID- 15474159
TI  - A novel complex t(2;5;13)(p23;q35;q14) in small cell variant type anaplastic
      large cell lymphoma with peripheral involvement.
AB  - We report the case of a 32-year-old woman who was diagnosed as having small cell
      variant type anaplastic large cell lymphoma with peripheral involvement. A
      cytogenetic study showed a complex translocation, t(2;5;13)(p23;q35;q14).
      Fluorescence in situ hybridization with ALK break-apart probes confirmed that the
      three-break rearrangement involves the ALK gene.

PMID- 15474160
TI  - Clinicoprognostic significance of pRb1 pathway alterations in uterine endometrial
      adenocarcinoma.
AB  - Components of the pRb1 pathway play a pivotal role in regulating the G1/S
      transition in the cell cycle. This study investigated the association between
      pRb1-cyclin D1-cdk4-p16INK4A pathway alterations and the clinical and prognostic
      utility for women affected by primary uterine endometrial adenocarcinoma (EC).
      The study population consisted of 50 cases of EC patients who were investigated
      for RB1 and CDKN2A (alias p16INK4A) gene alterations, as well as for the
      expression pattern of pathway proteins. Altogether, pRb1 pathway alterations were
      noted in 54% (27 of 50) of ECs, and more frequently in advanced-stage uterine
      carcinomas (P=0.024, Fisher exact test). Loss of heterozygosity abnormalities in
      RB1 and CKDN2A coexisted with altered cyclin D1-cdk4 complex immunoreactivity
      only in 2 patients, both less than 50 years of age. With respect to pRb1 pathway
      alterations, however, the recurrence rate was not significantly different
      (P=0.477; log-rank test). Our results suggest that the progression of uterine
      endometrial adenocarcinoma is generally accompanied by increased frequency of
      pRb1 pathway alterations. Alterations of the retinoblastoma pathway may not be
      necessarily associated with the recurrence of EC.

PMID- 15474161
TI  - Trisomy 6 in a child with acute megakaryoblastic leukemia (AML-M7).

PMID- 15474162
TI  - A case of i(11)(q10) as sole cytogenetic abnormality in a patient with acute
      lymphoblastic leukemia.

PMID- 15474163
TI  - Homer-PIKE complex: a novel link between mGluRI and PI 3-kinase.
AB  - Metabotropic glutamate (mGlu) receptors, a family of G-protein-coupled receptors,
      are thought to signal through the phospholipase and inositol (1,4,5)
      trisphosphate receptor system, or through the adenylyl cyclase and protein kinase
      C system. Rong et al. have recently identified a new phosphoinositide (PI) 3
      kinase enhancer (PIKE-L) that links group I mGlu receptors (mGluRI) to PI 3
      kinase through Homer proteins, adaptors that bind mGluRI. mGluRI agonists
      enhanced mGluRI-Homer-PIKE-L complex formation, leading to activation of PI 3
      kinase and inhibition of staurosporine-induced neuronal apoptosis. These results
      reveal a novel anti-apoptotic signaling mechanism that involves formation of an
      mGluRI signaling complex.

PMID- 15474164
TI  - A paradox in the evolution of primate vocal learning.
AB  - The importance of auditory feedback in the development of spoken language in
      humans is striking. Paradoxically, although auditory-feedback-dependent vocal
      plasticity has been shown in a variety of taxonomic groups, there is little
      evidence that our nearest relatives--non-human primates--require auditory
      feedback for the development of species-typical vocal signals. Because of the
      apparent lack of developmental plasticity in the vocal production system,
      neuroscientists have largely ignored the neural mechanisms of non-human primate
      vocal production and perception. Recently, the absence of evidence for vocal
      plasticity from developmental studies has been contrasted with evidence for vocal
      plasticity in adults. We argue that this new evidence makes non-human primate
      vocal behavior an attractive model system for neurobiological analysis.

PMID- 15474165
TI  - Neurons and glia: team players in axon guidance.
AB  - In the developing nervous system, growth cones follow specific trajectories to
      reach their target area and ultimately connect with their correct postsynaptic
      partners. This review focuses on studies in both Drosophila and vertebrates to
      highlight that mutual interactions between neurons and glia are essential in
      forming specific neuronal connections. Glia signal to neurons to direct
      pathfinding and targeting of axons, as well as to stabilize and refine axonal
      branches within the target area. Equally, neurons provide crucial information to
      glia, supporting their migration and correct positioning.

PMID- 15474166
TI  - GABAergic microcircuits in the neostriatum.
AB  - The vast majority of neostriatal neurons and intrinsic intrastriatal synapses are
      GABAergic, the latter arising from axon collaterals of spiny projection neurons
      and from GABAergic interneurons. An important feature of the functional
      organization of the neostriatum has long been assumed to be the existence of a
      widespread lateral inhibitory network mediated by the axon collaterals of spiny
      projection neurons. However, these collateral connections have recently been
      demonstrated electrophysiologically to be relatively weak--in contrast to
      feedforward interneuronal inhibition, which exerts strong effects on spike timing
      in spiny neurons. These new data are incompatible with current "winner-take-all"
      models of lateral inhibitory function in the neostriatum, and they force a
      modification of established concepts of the functional roles of feedback
      inhibition in this nucleus.

PMID- 15474167
TI  - Interneurons and triadic circuitry of the thalamus.
AB  - The thalamus is strategically placed to control the flow of information to cortex
      and thus conscious perception. A key player in this control is a local GABAergic
      interneuron that inhibits relay cells. This interneuron is especially interesting
      because, in addition to a conventional axonal output, most of its output is via
      distal dendrites. The latter seem to be electrotonically and thus functionally
      isolated from the soma and axon, and they enter into complex synaptic
      arrangements. It is proposed that, because of special synaptic properties of its
      dendritic outputs, this local GABAergic interneuron of the thalamus provides gain
      control for the relay cell and thereby keeps relay of information to cortex
      within a fairly linear regime.

PMID- 15474168
TI  - The neuroscience of tinnitus.
AB  - Tinnitus is an auditory phantom sensation (ringing of the ears) experienced when
      no external sound is present. Most but not all cases are associated with hearing
      loss induced by noise exposure or aging. Neuroscience research has begun to
      reveal how tinnitus is generated by the brain when hearing loss occurs, and to
      suggest new avenues for management and prevention of tinnitus following hearing
      injuries. Downregulation of intracortical inhibition induced by damage to the
      cochlea or to auditory projection pathways highlights neural processes that
      underlie the sensation of phantom sound.

PMID- 15474169
TI  - Genes, dopamine and cortical signal-to-noise ratio in schizophrenia.
AB  - A large body of phenomenological evidence implicates abnormal connectivity of
      brain macrocircuitry and microcircuitry in schizophrenia. Recent discoveries of
      susceptibility genes for schizophrenia have zeroed in on the synaptic signaling
      machinery of cortical microcircuits as fundamental to disease causation and have
      militated for further revision of the role of dopamine in this illness. Dopamine,
      long implicated in psychosis and in antipsychotic drug effects, is crucial in
      optimizing signal-to-noise ratio of local cortical microcircuits. This action of
      dopamine is achieved principally by D1- and D2-receptor-mediated effects on
      pyramidal and local circuit neurons, which mediate neuronal excitability and
      recurrent inhibition and thus contribute to the stability of cortical
      representations of external and internal stimuli. In schizophrenia, an abnormal
      cortical dopamine D1/D2 activation ratio - in concert with, and in part related
      to, altered GABA and glutamate transmission - appears to interfere crucially with
      this process.

PMID- 15474170
TI  - Genetic mouse models of Huntington's and Parkinson's diseases: illuminating but
      imperfect.
AB  - Genetic mouse models based on identification of genes that cause Huntington's and
      Parkinson's diseases have revolutionized understanding of the mechanistic
      pathophysiological progression of these disorders. These models allow the
      earliest manifestations of the diseases to be identified, and they display
      behavioral, neuropathological and electrophysiological deficits that can be
      followed over time in mechanistic and drug studies. An intriguing feature is that
      they do not reproduce the relatively selective and massive cell loss
      characterizing the human diseases. There is more information on Huntington's
      disease models because the disorder involves a single gene that was identified
      over ten years ago; genetic mutations causing Parkinson's disease are rare and
      were discovered more recently, and models of the disease have been generated only
      within the past few years.

PMID- 15474171
TI  - Time intervals production in tapping and oscillatory motion.
AB  - We applied spectral analysis on series of time intervals produced in a
      synchronization-continuation experiment. In the first condition intervals were
      produced by finger tapping, and in the second by an oscillatory motion of the
      hand. Results obtained in tapping were consistent with a discrete, event-based
      timing model. In the oscillatory condition, the spectra suggested a continuous,
      dynamic timing mechanism, based on the regulation of effector stiffness. It is
      concluded that the oscillatory character of movement can offer an important
      resource for timing control. The use of an event-based timing control such as
      postulated in the Wing-Kristoffersson model could be restricted to a quite
      limited class of rhythmic tasks, characterized by the concatenation of discrete
      events.

PMID- 15474172
TI  - Respiration and postural sway: detection of phase synchronizations and
      interactions.
AB  - The aim of the central nervous system in upright stance is to control an
      intrinsically unstable plant. Internal disturbances, such as haemodynamics and
      respiration, constitute an endogenous threat to equilibrium. The way CNS reacts
      to those perturbations was studied in this work, through the analysis of summary
      scores taken from posturographic and pneumographic data. Signals were recorded
      simultaneously during trials administered on a sample population of healthy young
      adults, while sitting and standing and at paced and spontaneous uncontrolled
      breathing. The extraction of posturographic and pneumographic parameters was
      accompanied by the utilization of techniques for the detection of phase
      synchronization in bivariate data, and the extraction of an interaction index,
      the mutual information MI. The effects of the biomechanical condition and
      respiratory amplitude on MI and summary measures were tested with a two-way
      ANOVA. Summary scores clearly depend on posture condition. Synchronization
      between breath and postural sway is always present, depends on both biomechanical
      condition and respiratory threat, and cannot be reduced to a simple linear
      relation.

PMID- 15474173
TI  - Instant of chair-rise lift-off can be predicted by foot-floor reaction forces.
AB  - OBJECTIVE: To develop a predictive model of the lift-off event during chair rise
      in healthy subjects, using foot-floor reaction forces. BACKGROUND: An important
      event during chair rise is lift-off from the seat: the transition from the
      inherently stable three-point contact to the unstable two-point contact. There is
      no consistent or generally agreed upon method for estimating the time of lift-off
      when an instrumented seat is unavailable. METHODS: Twenty healthy volunteers were
      divided into a testing set and training set. Each subject performed repeated
      chair rise trials at different speeds. Seat-floor and foot-floor forces, recorded
      with two force platforms, were used to develop a model of the lift-off event.
      RESULTS: The magnitude of the vertical foot-floor reaction at lift-off (F0VF) was
      linearly related (R2 = 0.71, P < 0.001) to the peak vertical foot-floor reaction
      force (FMVF). A linear model was developed for the training group, which enabled
      prediction of lift-off time for the testing group with an absolute average error
      of 6 ms (about 1 data frame at 150 Hz). The linear model derived for the entire
      sample was: F0VF = 28.14 + FMVF * (0.6434). CONCLUSIONS: The lift-off event for
      healthy subjects performing chair rise can be accurately predicted from foot
      floor reaction forces, without requiring an instrumented seat.

PMID- 15474174
TI  - Modeling dynamic resource utilization in populations with unique constraints:
      preadolescents with and without Down syndrome.
AB  - In this study we used a damped inverted pendulum and spring with an escapement
      function model to compare the global levels of stiffness and forcing used by 12
      preadolescents with Down syndrome (DS) and 12 with typical development (TD).
      Participants walked overground at their self-selected speed and on a treadmill at
      speeds slower and faster than overground. Children with DS, who are characterized
      as hypotonic with reduced capacity for producing muscle force, exhibited
      significantly higher levels of stiffness and forcing (angular impulse) when
      walking on the treadmill and higher forcing but not stiffness overground, than
      children with TD. Both groups adapted to imposed speed increases similarly by
      increasing their global stiffness and angular impulse. We propose children with
      DS increased stiffness in order to overcome their hypotonia and joint laxity,
      thus, optimizing on stability, rather than metabolic efficiency. Higher angular
      impulse values for children with DS may reflect higher energy cost associated
      with increasing stiffness and their inherent biomechanical and physiological
      characteristics that reduce efficiency. We conclude that the inverted pendulum
      and spring with escapement function model is a useful tool for uncovering
      solutions to movement problems-solutions that reflect the dynamic resources of
      the individual and ones that are discovered, rather than prescribed.

PMID- 15474175
TI  - Children with low motor ability have lower visual-motor integration ability but
      unaffected perceptual skills.
AB  - The purpose of this study was to examine perceptual, visual-motor abilities and
      intellectual skills in children with low, average and above average motor
      abilities. The participants were 144 children (aged 6-10 years) attending
      elementary school. Three groups of children were identified on the basis of their
      performance at the TGMD (Test of Gross Motor Development; [Ulrich, D.A. (1985).
      TGMD, Test of Gross Motor Development. Austin, Texas: PRO-ED. Edizione Italiana a
      cura di D. Ianes, TEST TGM. Test di valutazione delle abilita grosso-motorie.
      1994, Trento: Edizioni Centro Studi Erickson]). Each child received an
      intelligence test (K-BIT; [Kaufman, A.S., & Kaufman, N.L. (1990). K-BIT. Kaufman
      Brief Intelligence Test. Circle Pines, MN: American Guidance Service]) and was
      evaluated for perceptual and visual-motor integration abilities (DTVP; [Hammill,
      D.D., Pearson, N.A., & Voress, J.K. (1993). Developmental Test of Visual
      Perception (2nd ed.). Austin, Texas: PRO-ED. Edizione Italiana a cura di D.
      Ianes, TEST TPV. Test di percezione visiva e integrazione visuo-motoria. Trento:
      Edizioni Centro Studi Erickson]). Results highlight a significant difference in
      visual-motor integration between children with high and low gross-motor
      abilities, in the absence of significant differences in perceptual skills or
      intellectual ability. The findings are discussed with reference to the concept of
      atypical brain development [Gilger, J.W., & Kaplan, B.J. (2001). Atypical brain
      development: A conceptual framework for understanding developmental learning
      disabilities. Developmental Neuropsychology, 20, 465].

PMID- 15474176
TI  - Anticipatory balance control is affected by loadless training experiences.
AB  - The main purpose of this study was to identify whether a lot of sports training
      had any effect on the balance control associated with a leg movement. The nature
      of the training experience was also an important concern and we chose subject who
      had undergone specific training experience in absence of equilibrium constraints.
      To this end a comparison between control (untrained) subjects, triathletes and
      swimmers was designed to establish whether a general training in sports
      (triathletes) or a specific loadless training (swimmers), leads to differences in
      the balance control. A leg movement is preceded by a shift of the center of mass
      (CM) towards the supporting side to maintain equilibrium and forward to create
      the condition for progression. To provide an acceleration of the CM sideward and
      forward, an initial displacement of the center of pressure (CP) towards the
      moving limb and in posterior direction was performed. Interestingly, the lateral
      pressure onto the ground was greater increased in swimmers in both leg raising
      and obstacle avoidance tasks compared to the control group and/or triathletes
      whereas the backward CP shift in all group was the same. The initial control of
      the CM shift is very different in swimmers compared to triathletes and controls.
      The increased lateral pressure onto the ground in swimmers may be a result of a
      prolonged training in water. This suggests that prolonged training in the absence
      of equilibrium constraints has more of an effect on balance control than a
      prolonged general training. In addition, the lack of differences in the backward
      CP shift suggests that M/L and A/P controls support two functional goals:
      equilibrium maintenance and movement initiation.

PMID- 15474177
TI  - Coordination changes in the early stages of learning to cascade juggle.
AB  - The experiment was setup to examine the coordination changes in assembling the
      movement form of 3-ball cascade juggling. Eight adult participants learned to
      juggle over 4 weeks of practice. Juggling scores were recorded at each session
      and performance was videotaped at eight selected sessions for purposes of
      movement analysis. Once the basic spatial and temporal constraints on cascade
      juggling were satisfied, and the figure-8 juggling mode was established, temporal
      modulations of the relative motions of the hands were emphasized. All
      participants learned to juggle and the increase over practice in the number of
      consecutive balls caught was best fit with a power law. The non-proportional rate
      of performance increment was consistent with the qualitative changes in the form
      of the hand and ball movement kinematics that occurred over practice.

PMID- 15474178
TI  - Temporal and spatial factors reflecting performance improvement during learning
      three-ball cascade juggling.
AB  - Beek and van Santvoord [Beek, P. J., & van Santvoord, A. A. M. (1992). Journal of
      Motor Behavior, 24, 85-94] proposed a three-stage model of learning to juggle
      based on group analyses of temporal measures. Here, we examined in detail how the
      temporal and spatial features of juggling evolved in eight individual
      participants progressing from the second to the third stage of learning. During
      the second stage, the dwell ratio, defined as the ratio of the time that the
      juggler holds a ball between catch and toss and the hand cycle time (HCT), was
      stable when it was about 0.83. The subjects with a dwell ratio near this value
      and controlled throws exhibited stable juggling, whereas the subjects with a
      dwell ratio of 0.80 or smaller exhibited unstable juggling. Compared to the
      former group, the latter group had a longer time from the throw of a ball to the
      arrival at its zenith (TZ), and a shorter time between the arrival of an airborne
      ball at its zenith and the subsequent throw (IZR). The latter group also
      exhibited larger variability in the dwell ratio and IZR. With practice, the
      subjects appropriated, on average, the duration of TZ and IZR to the dwell ratio
      and improved the ability to accurately throw balls by changing the motions of the
      limb segments involved. Although these changes helped to stabilize the
      performance during the second stage, the variability problem was not sufficiently
      resolved. Only two out of eight subjects passed on to the third stage by the last
      (10th) Session. They achieved small variability in IZR, dwell ratio, and flight
      paths of the ball while juggling with short HCTs and small dwell ratios. These
      results suggest that the reduction of variability in these variables was
      essential to pass on to the third stage.

PMID- 15474179
TI  - Control of vancomycin-resistant enterococci in a hospital: a five-year experience
      in a Taiwanese teaching hospital.
AB  - In order to prevent transmission of hospital-acquired vancomycin-resistant
      enterococci (VRE), the infection control team (ICT) of the National Taiwan
      University Hospital (NTUH) introduced practical guidelines from January 1997 to
      June 2000. All patients at NTUH found to be infected or colonized with VRE were
      placed in strict contact and cohort isolation. Surveillance cultures were
      obtained from other patients in close proximity in order to determine any spread
      of VRE. If identified, these patients were also placed in contact and cohort
      isolation, and their isolates were subjected to antimicrobial susceptibility
      testing and molecular typing by pulsed-field gel electrophoresis. During this
      period, 20 patients were found to have VRE. Based on typing results, there were
      three occasions where the same VRE strain had spread between index patients and
      roommates or patients staying in neighbouring rooms. No further spread occurred
      after applying strict contact isolation for these patients. The hospital-acquired
      VRE infection rate was around 0.03 to 0.09 per 1000 discharges during the
      intervention period. After July 2000, however, members of the ICT did not
      actively monitor or implement any interventions to control VRE. The rate then
      increased to 0.20 per 1000 discharges in 2001. This study suggests that
      interventions for the control of VRE, based on the guidelines from the Hospital
      Infection Control Practice Advisory Committee, are effective for control of VRE
      spread. Failure to adhere to these guidelines may result in an increase in
      hospital-acquired VRE.

PMID- 15474180
TI  - An investigation of contact transmission of methicillin-resistant Staphylococcus
      aureus.
AB  - Hand hygiene is critical in the healthcare setting and it is believed that
      methicillin-resistant Staphylococcus aureus (MRSA), for example, is transmitted
      from patient to patient largely via the hands of health professionals. A study
      has been carried out at a large teaching hospital to estimate how often the
      gloves of a healthcare worker are contaminated with MRSA after contact with a
      colonized patient. The effectiveness of handwashing procedures to decontaminate
      the health professionals' hands was also investigated, together with how well
      different healthcare professional groups complied with handwashing procedures.
      The study showed that about 17% (9-25%) of contacts between a healthcare worker
      and a MRSA-colonized patient results in transmission of MRSA from a patient to
      the gloves of a healthcare worker. Different health professional groups have
      different rates of compliance with infection control procedures. Non-contact
      staff (cleaners, food services) had the shortest handwashing times. In this
      study, glove use compliance rates were 75% or above in all healthcare worker
      groups except doctors whose compliance was only 27%.

PMID- 15474181
TI  - Changing epidemiology of methicillin-resistant Staphylococcus aureus in Finland.
AB  - Data on methicillin-resistant Staphylococcus aureus (MRSA) cases notified to the
      National Infectious Disease Register (NIDR) and antibiotic resistance profiles of
      MRSA isolates sent to the national reference laboratory between 1997 and 2002
      were analysed. In addition, the diagnostic methods used for MRSA identification
      in Finnish microbiology laboratories, the number of MRSA screening specimens
      studied, and the MRSA situation in long-term care facilities in 2001 were
      reviewed. MRSA cases notified to the NIDR rose from 120 in 1997 to 597 in 2002
      (from 2.3 to 11.5 cases per 100,000 population). The increase was greatest in
      elderly people and outside Helsinki metropolitan area, in the districts where the
      proportion of non-multiresistant strains was most prominent. The National
      Committee for Clinical Laboratory Standard's guidelines for the oxacillin disk
      diffusion test were followed, except for the incubation temperature and time,
      which may have hindered detection of some MRSA strains. There was a wide
      geographic variation in the rates of MRSA, but this was not related to screening
      activity. MRSA isolates from long-term facilities accounted for more than half of
      the notifications to the NIDR in 2001.

PMID- 15474182
TI  - Comparison of two in vivo and two ex vivo tests to assess the antibacterial
      activity of several antiseptics.
AB  - An ex vivo test was adapted to mimic the in vivo conditions of testing antiseptic
      activity on human forearms and in the European Standard Hygienic Handwash Test
      (BSEN 1499). The study was to validate the ex vivo protocols using 4.8% (w/v)
      para-chloro-meta-xylenol (PCMX, neat Dettol), 0.5% (w/v) triclosan in 70% (v/v)
      isopropanol, and 2% (v/v) povidone-iodine against a high bacterial inoculum
      (>10(8) cfu/mL) of Escherichia coli NCTC 10538. Two ex vivo tests using human
      skin samples, including one introducing a mechanical rubbing effect, were
      compared with two corresponding in vivo tests (the forearm test and the BSEN
      handwashing test). All antiseptics assessed in vivo (forearm and handwash tests)
      produced reductions in bacterial counts that were significantly greater than
      those for the non-medicated soft soap control. When assessed ex vivo without
      rubbing, only PCMX and povidone-iodine achieved reductions significantly greater
      than soft soap. When assessed ex vivo with mechanical rubbing, only PCMX and
      triclosan achieved reductions significantly greater than soft soap. Overall, the
      antiseptics at the concentrations tested were more active when tested in vivo
      than ex vivo. The addition of a mechanical effect, either in vivo by the
      volunteers washing their hands or ex vivo by a drill rubbing two skin samples
      against each other, produced a significantly greater reduction in bacterial
      concentrations. The ex vivo tests were easily adapted to mimic in vivo protocols.
      The value of such tests, particularly the one that includes a rubbing effect, may
      be significant as they avoid the need for human volunteers.

PMID- 15474183
TI  - A nosocomial outbreak of Salmonella enteritidis associated with lyophilized
      enteral nutrition.
AB  - Outbreaks of Salmonella spp. gastro-enteritis in hospitals are of concern because
      of the increased susceptibility of patients and associated high morbidity. This
      study is a report of a nosocomial outbreak of Salmonella enteritidis associated
      with enteral nutrition. In December 1999, one sample of enteral feed tested
      positive for S. enteritidis. During the subsequent 6 weeks, eight cases of
      nosocomial salmonellosis occurred. Patients involved in the outbreak were aged 19
      79 years (median = 36.5), and salmonella was isolated from the blood of two
      patients. All patients were receiving enteral nutrition at the time and all had
      diarrhoea. Three patients died. All 13 employees of the Nutrition Department were
      asymptomatic and their stool samples were negative. Environmental and water
      samples were also negative. The diet, however, contained lyophilized egg albumin.
      Molecular typing showed that the isolates of seven patients were
      indistinguishable from the one obtained from the enteral diet. It was thought
      that the nosocomial salmonellosis probably occurred due to the use of a
      commercial lyophilized diet. Another method of processing diets may be necessary
      to ensure patient safety.

PMID- 15474184
TI  - Strategies for the diagnosis and treatment of bacteraemia in children with
      central venous catheters: an analysis.
AB  - The aim of this study was to analyse the diagnostic, empirical and therapeutic
      strategies adopted when a blood culture from a hospitalized child with a central
      venous catheter is 'positive', and to assess whether practices complied with the
      consensus adopted in our hospital, inspired by published recommendations. One
      hundred and ten cases of bacteraemia were studied prospectively. Investigations
      to determine whether the catheter was the cause of infection were carried out in
      45% of cases, and the catheter was removed as recommended in 39% of cases. Of the
      patients that received empirical treatment, 56% received broad-spectrum
      antibiotics with no apparent clinical justification. Following susceptibility
      testing on the isolated strain, the antibiotic treatment was considered to be
      appropriate in 58% of cases. Overall, compliance with the consensus
      recommendations was poor. This was partly due to the high turnover rate of
      antibiotic prescribers.

PMID- 15474185
TI  - Intensive-care-unit-acquired bloodstream infections in a regional critically ill
      population.
AB  - Bloodstream infection (BSI) is a serious complication of critical illness but it
      is uncertain whether acquisition of BSI in the intensive care unit (ICU)
      increases the risk of death. A study was conducted among all Calgary health
      region (population approximately 1 million) adults admitted to ICUs for 48 h or
      more during a three-year period to investigate the occurrence, microbiology and
      risk factors for developing an ICU-acquired BSI and to determine whether these
      infections independently predict mortality. One hundred and ninety-nine ICU
      acquired BSI episodes occurred during 4933 ICU admissions for a cumulative
      incidence of 4% and an incidence density of 5.4 per 1000 ICU days. The most
      common isolates were Staphylococcus aureus (18%), coagulase-negative
      staphylococci (11%), and Enterococcus faecalis (8%); 12% of infections were due
      to antimicrobial-resistant bacteria. Admission to the regional
      neurosurgery/trauma ICU [odds ratio (OR) 2.86; 95% confidence interval (CI) 2.10
      3.90] and increasing Acute Physiology and Chronic Health Evaluation II (APACHE
      II) score (OR 1.05 per point, 95% CI 1.03-1.07) were associated with higher risk,
      whereas a surgical diagnosis (OR 0.69; 95% CI 0.52-0.93) was associated with
      lower risk of developing ICU-acquired BSI in logistic regression analysis. The
      crude in-hospital death rate was 45% for patients with ICU-acquired BSI compared
      with 21% for those without (P < 0.0001) Development of an ICU-acquired BSI was an
      independent risk factor for death (OR 1.79; 95% CI 1.3-2.5) and increases the
      risk of dying from critical illness.

PMID- 15474186
TI  - Bacteriological screening of expressed breast milk revealed a high rate of
      bacterial contamination in Chinese women.
AB  - A screening programme for expressed breast milk (EBM) revealed the alarming fact
      that our study group had the highest rate of contamination ever reported. The
      programme started in July 2002 and involved a group of Chinese women whose
      premature babies were in the neonatal intensive care unit. EBM was considered to
      be contaminated if there was any growth of pathogens, including Gram-negative
      bacteria, enterococci or Staphylococcus aureus, or if the total bacterial count
      was >10(5) cfu/mL. Of 59 samples from 23 mothers, 63% were contaminated. This
      high contamination rate could be due to the Chinese tradition of avoiding bathing
      for one month after childbirth. Previous studies have shown that feeding EBM
      rather than premature infant formula milk has advantages in terms of decreased
      incidence of necrotizing enterocolitis and neonatal sepsis. However, in this
      population, with such a high incidence of contaminated EBM, this may not be the
      case. Further studies to compare EBM with premature infant formula in this
      population are required.

PMID- 15474187
TI  - Effect of peracetic acid and aldehyde disinfectants on biofilm.
AB  - The effects of two aldehyde (Cidex, Endosporine) and four peracetic acid (PAA)
      (Nu Cidex, Anioxyde 1000, Hydraseptic, Peralkan) disinfectants on an Escherichia
      coli biofilm model were studied. The biofilm was prepared in glass tubes, and
      evaluated indirectly using a colourimetric method. The ability of the
      disinfectants to fix or remove the biofilm from tubes was determined by their
      detergent activity (DA). The two aldehyde derivatives and two of the PAA (Nu
      Cidex, Anioxyde 1000) agents fixed the biofilm. However, the effects of
      Hydraseptic and Peralkan were equivalent to the control (sterile water).
      Regardless of their disinfectant activity, PAA agents display different DAs that
      could be used to select the weakest biofilm-fixing agents. Users should be
      concerned about the efficiency of the cleaning stage of medical devices, and when
      choosing a PAA product, non-fixing ability should be considered in addition to
      antimicrobial activity.

PMID- 15474188
TI  - Provision of safe potable water for immunocompromised patients in hospital.
AB  - We conducted a survey of hospital drinking water provision for patients with
      immunocompromising conditions in 15 Trusts in the north of England. Ten trusts
      replied, reporting on provision of drinking water in 14 separate units. Of these,
      nine provided only tap water to all patients, irrespective of underlying
      condition. In two units, iced water, with ice from commercially available makers,
      was used. Five units distinguished between neutropenic and non-neutropenic
      patients, with the former group receiving cooled, boiled water (three units),
      sterile water and sterile water or carbonated water (one unit each). No unit
      provided filtered water. Water in jugs was changed daily, twice daily or only
      when empty in seven, three and four units, respectively. On 10 units, patients
      were allowed to provide their own drinking water, but no unit provided written
      advice to patients on potable water. A survey within our own Trust revealed
      similar inter-unit disparity. The options for potable water provision were
      reviewed, taking into account: microbiological quality, organoleptic (perceived
      taste/smell) acceptability, cost and factors relating to staff safety and patient
      confidentiality [as it was possible for human immunodeficiency virus (HIV)
      seropositive patients on some wards to be identified because they were provided
      with cooled, boiled water]. It concluded that end-line commercially available
      water filters were the optimal way to provide drinking water to immunocompromised
      patients in hospital.

PMID- 15474189
TI  - Pseudo-outbreak of Burkholderia cepacia in a neonatal intensive care unit.

PMID- 15474190
TI  - An outbreak of imipenem-resistant Pseudomonas aeruginosa in an intensive care
      unit.

PMID- 15474191
TI  - Role of isolation unit in MRSA control.

PMID- 15474192
TI  - From legionnaire to guerrilla combatant: suppression of Legionella pneumophila in
      a hospital cold water supply.

PMID- 15474193
TI  - Re: Nosocomial outbreak of norovirus gastroenteritis and investigation of ABO
      histo-blood group type in infected staff and patients.

PMID- 15474194
TI  - Vaccinated but not immunized: protection against hepatitis B in medical staff in
      the developing world.

PMID- 15474195
TI  - There is not enough evidence to recommend the widespread use of topical
      antimicrobials on the umbilical cord stump.

PMID- 15474196
TI  - Changes at Social Science & Medicine.

PMID- 15474197
TI  - Income inequality and self-rated health in US metropolitan areas: a multi-level
      analysis.
AB  - Income inequality has been found to affect health in a number of international
      and cross-national studies. Using data from a telephone survey of adults in the
      United States, this study analyzed the effect of metropolitan level income
      inequality on self-rated health. It combined individual data from the 2000
      Behavioral Risk Factor Surveillance System with metropolitan level income data
      from the 2000 Census. After controlling for smoking, age, education, Black race,
      Hispanic ethnicity, sex, household income, and metropolitan area per capita
      income, this study found that for each 1 point rise in the GINI index (on a
      hundred point scale) the risk of reporting Fair or Poor self-rated health
      increased by 4.0% (95% confidence interval 1.6-6.5%). Given that self-rated
      health is a good predictor of morbidity and mortality, this suggests that
      metropolitan area income inequality is affecting the health of US adults.

PMID- 15474198
TI  - A multilevel analysis of race, community disadvantage, and body mass index among
      adults in the US.
AB  - This study examined the contributions of both individual socioeconomic status
      (SES) and community disadvantage in explaining the higher body mass index (BMI)
      of black adults in the US. Data from a national survey of adults (1986 American's
      Changing Lives Study) were combined with tract-level community data from the 1980
      census. Results of multilevel regression analyses showed that black women had an
      age-adjusted BMI score three points higher than non-black women. Individual SES
      (income, education, assets) was negatively associated with BMI in women, but it
      only reduced the association between race and BMI from 2.99 to 2.50. Adding
      community socioeconomic disadvantage index further reduced the race coefficient
      slightly from 2.50 to 2.21. Nevertheless, living in communities with higher
      socioeconomic disadvantage was associated with higher BMI net of age, race,
      individual SES, smoking, physical activity, stress, and social support. Community
      income inequality (Gini) had an independent positive association with BMI, but
      did not substantially reduce racial differences among women. Community percent
      black was not associated with BMI. Results for men demonstrated no statistically
      significant racial differences in BMI, and no association between BMI and either
      individual SES or community disadvantage. Although individual SES and community
      socioeconomic disadvantage each partly explained the higher average BMI among
      black women, clear racial disparities persisted. Moreover, race, individual SES,
      community socioeconomic disadvantage, and individual health behaviors were each
      independent predictors of BMI among women. Unexplained within- and between
      community variance in BMI remained among both women and men, with most
      unexplained variation due to within-community variance. Because our evidence for
      women suggests that the determinants of obesity are multiple and multilevel,
      attempts to address this growing social problem will similarly require a multi
      faceted and multilevel approach.

PMID- 15474199
TI  - Municipal socioeconomic status and mortality in Japan: sex and age differences,
      and trends in 1973-1998.
AB  - The purpose of this study was to examine the sex and age differences and the time
      trends in the association between municipal socioeconomic status (SES) and all
      cause mortality across Japan from 1973 to 1998. Sex-specific mortality of
      municipalities (N=3319 in 1995) by age groups (total, under 75-year, and over 75
      year populations) was linked to municipal SES indicators related to income,
      education, unemployment and living space, and two SES composite indices
      formulated by principle component analysis (Index 1 related to lower income and
      education, and Index 2 related to unemployment and overcrowding). The relation
      was assessed using mortality gradients by SES quintiles and Bayesian hierarchical
      Poisson regression. The results showed that a lower SES was related to higher
      mortality for all SES indicators and composite indices. The mortality gradient
      was steeper for the under 75-year population than the total and over 75-year
      populations, and the relation between mortality and income- and education-related
      indicators/index was stronger for males than for females. The time trend showed
      an increase in the relation for Index 2, while a decrease for Index 1. This study
      demonstrated that lower municipal SES had an adverse influence on population
      health, and the influence was marked for males and premature death. Although a
      substantial health disadvantage still remained in lower SES areas, the impact of
      SES factors on geographical health variation changed over time; the association
      with mortality has weakened for income and education, while it has strengthened
      for unemployment and living space.

PMID- 15474200
TI  - Social capital in working life and the health of employees.
AB  - It is commonly assumed that social capital influences health, but only few
      studies have examined this hypothesis in the context of the workplace. The
      present prospective cohort study of 6028 public sector employees in Finland
      investigated social capital as a workplace characteristic which potentially
      affects employee health. The two indicators of social capital were trust in the
      labour market, measured by security of the employment contract, and trust in co
      worker support. Self-rated health status and psychological distress were used as
      indicators of health. The combination of subsidised job contract and low co
      worker support (i.e. the lowest category of social capital) was associated with
      poorer health prospects than the combination of permanent employment and high
      support (the highest social capital category) in an age-adjusted model, but this
      association disappeared in logistic regression analysis adjusted by
      sociodemographic background factors and baseline health. Fixed-term employment
      predicted better self-rated health and less psychological distress when compared
      with permanent employment. Co-worker support was most common in permanent and
      least common in subsidised employees and it was associated with better self-rated
      health in women. Our findings suggest only partial support for the hypothesis of
      work-related social capital as a health resource.

PMID- 15474201
TI  - Inpatient/outpatient health care costs and remaining years of life--effect of
      decreasing mortality on future acute health care demand.
AB  - The article introduces a method that may be used to estimate how demographic
      changes may affect future demand for inpatient/outpatient health care. The method
      is useful in order to refine estimation of demographic influence on demand in the
      process of health human resources planning. Empirical evidence focuses on the
      connection between health care costs and remaining years of life. We estimate the
      demographically determined rise in inpatient/outpatient health care demand in
      Sweden in the period 2000-2030. The increase arrived at, by means of our method,
      is circa 37% lower than estimates done with a simple demographical extrapolation,
      which does not take the decreasing mortality pattern into account.

PMID- 15474202
TI  - Preferences in end-of-life care of older persons: after-death interviews with
      proxy respondents.
AB  - This population-based study employing after-death interviews with proxies
      describes older persons' preferences regarding medical care at the end of life.
      Interviews were held with 270 proxy respondents of 342 deceased persons (age
      range 59-91) in the Netherlands, The deceased were respondents to the
      Longitudinal Aging Study Amsterdam. The prevalence of advance directives (ADs),
      preferences for medical decisions at the end of life (i.e. withholding treatment,
      physician-assisted suicide euthanasia) and preferences about the focus of
      treatment in the last week of life (i.e. comfort care versus extending life) were
      examined. Written ADs were present in 14% of the sample. A quarter had designated
      a surrogate decision-maker. Co-morbidity and perceived self-efficacy (PSE) were
      positively associated with ADs. About half the sample had expressed a preference
      in favour or against one or more medical decisions at the end of life. Predictors
      positively associated with expressing a preference were co-morbidity, dying from
      cancer, and PSE. Being religious was negatively associated with expressing a
      preference. The knowledge of the proxy regarding the older person's preference
      for the focus of treatment was dependent on the patient's symptom burden as
      perceived by the proxy. The majority of older persons had died without either an
      AD, or having expressed preferences for end-of-life care. Stimulating the
      formulation of ADs may help professionals who work with older people to
      understand these preferences better, especially in the case of non-cancer
      patients and those with low PSE.

PMID- 15474203
TI  - Gender and use of health care among older adults in Egypt and Tunisia.
AB  - In Western industrialized countries, women report using health services more
      often than do men. We explore the applicability of existing theory to explain
      gender differences in use of health care among older adults in Egypt and Tunisia,
      where females have received less health care than males in early life. Findings
      show that women report visiting providers and using medications more often than
      do men; however, adjusted odds of visiting doctors are comparable for women and
      men in Tunisia and lower for women than men in Egypt. Odds of using health care
      are higher for women than men among those reporting no morbidity or functional
      impairment, but these relative odds diminish or reverse among those reporting
      multiple morbidities or severe impairments. The contributions of subjective and
      objective illness, quality of social support, and availability of services on
      gender differences in care in later life should be assessed in these and other
      settings where girls' excess mortality persists.

PMID- 15474204
TI  - Gender and age inequity in the provision of coronary revascularisation in England
      in the 1990s: is it getting better?
AB  - Although the mortality and incidence of coronary heart disease (CHD) in England
      and Wales has declined in recent years, an ageing population has contributed to
      keeping the prevalence of CHD largely unchanged. Evidence suggests that
      revascularisation procedures have contributed not only to this decline in
      mortality, but also to the decline in morbidity from heart disease, and to
      improvements in quality of life, even in old age. Despite clinical evidence of
      benefit, revascularisation is less often provided for older people and for women.
      This paper considers the equity of the provision of revascularisation according
      to need by gender and age using the Hospital Episodes Statistics (HES) database
      which includes all NHS hospital admissions in England. Trends from 1991 to 1999
      were examined comparing admissions for acute myocardial infarction (as a proxy
      indicator of need in the absence of direct measures) and the procedures coronary
      artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty
      (PTCA). The rates of CABG and PTCA have increased dramatically by 72% and 48%,
      respectively, between 1991/3 and 1997/9. Making allowance for differences in
      need, to achieve equitable provision with men, over 12,000 extra CABG and over
      5000 PTCA procedures would be required for women, amounting to 19% and 10%
      increases in the total volume of each procedure, respectively. Similarly,
      attempting to meet need up to the age of 79 years would require over 13,000 extra
      CABG and over 13,000 PTCA procedures for men, and an additional 14,300 CABG and
      almost 10,000 extra PTCA procedures for women, representing 42% and 40% increases
      in CABG and PTCA, respectively. As women tend to present with CHD at older ages
      this indicates that they may be the victims of a 'double whammy' of inequity.
      Moreover, these inequities have remained constant through the study period.
      Possible explanations for this shortfall of provision are proposed.

PMID- 15474205
TI  - Acculturation and physical activity among North Carolina Latina immigrants.
AB  - The objective of this study was to examine the association between acculturation
      and physical activity among first generation Latina (Hispanic women) immigrants
      living in North Carolina. As part of the multi-site Women's Cardiovascular Health
      Network, 671 first generation Latina immigrants 20-50 years of age completed in
      person interviews on physical activity, acculturation (measured by a language
      scale, length of residence in the US, and age at arrival in the US) and other
      potential individual and contextual correlates of physical activity. All
      statistical models were adjusted for age, general health, number of children in
      the home, marital status, and education, with self-reported physical activity as
      the dependent variable. Among participants, 37.4% met recommendations for
      physical activity, 41.9% reported insufficient activity, and 20.7% reported no
      moderate or vigorous activity. Latinas with higher English language acculturation
      were more likely to be physically active than women with lower English language
      acculturation. Likewise, women who arrived to the US when they were younger than
      25 years were more likely to be physically active than women who arrived when
      they were 25 years or older. Length of residence in the US was not associated
      with physical activity. These relationships persisted when restricting the sample
      to Mexican born women. We conclude that among first generation immigrants living
      in North Carolina, those with higher English language acculturation or who
      arrived to the US at younger ages were more likely to report being physically
      active. These findings suggest that future epidemiologic studies and physical
      activity interventions should measure and tailor programs based on English
      language use and age of arrival to the US among Latina immigrants.

PMID- 15474206
TI  - Health pessimism among black and white adults: the role of interpersonal and
      institutional maltreatment.
AB  - Using data from the 1995 Detroit Area Study (N=1106) this paper finds that black
      adults report significantly worse self-rated health when compared to whites with
      similar levels of self-reported morbidity. This relationship, called health
      pessimism, persists despite statistical controls for age, gender, socioeconomic
      status, health care access, and health related behaviors. Interpersonal
      maltreatment is found to be positively associated with health pessimism and more
      importantly, when comparing adults who perceive similar levels of maltreatment,
      white and black adults do not differ with respect to health pessimism. This
      suggests that the increased risk of health pessimism among black adults is due in
      part to race differences in the perception of interpersonal maltreatment.

PMID- 15474207
TI  - Single mothers and the use of professionals for mental health care reasons.
AB  - In the present study, we examine whether higher rates of mental health service
      use observed among single-parent mothers is due to greater need (psychopathology)
      or other factors (predisposing and enabling characteristics) using a socio
      behavioural model of health care use. We use data from two large surveys in
      Canada (the 1994-95 National Population Health Survey and the 1990 Ontario Mental
      Health Supplement). The bivariate results from both surveys revealed that single
      parent mothers were two to three times more likely than married mothers to have
      sought professional help for mental health reasons over a 12-month period.
      Multivariate analyses showed that differences in predisposing and enabling
      characteristics between single and married mothers accounted for very little of
      the relationship between family structure and service use. Rather, differences in
      the prevalence of psychiatric disorders accounted for the higher use of services
      among single mothers. Single mothers are more likely than married mothers to seek
      professional help for mental health concerns. The use of services appears
      equitable in that need (higher rates of psychopathology) is the major factor
      differentiating use between married and single mothers. Further work should
      examine differences in pathways into formal care between single and married
      mothers.

PMID- 15474208
TI  - Understanding of informed consent in a low-income setting: three case studies
      from the Kenyan Coast.
AB  - In our research unit on the Kenyan Coast, parents sign consent for over 4000
      children to be involved in research activities every year. Children are recruited
      into studies ranging from purely observational research to the testing of new
      procedures and drugs. Thousands more community members consent verbally or in
      writing to the interviews and sometimes invasive procedures required in community
      based research. Although every study and consent form is reviewed in advance by
      independent national and international committees, the views and understanding of
      the 'subjects' of these activities had not been documented before this study. In
      this paper, we focus on participant understanding of one field-based and two
      hospital-based studies, all of which involve blood sampling. The findings
      highlight a range of inter-related issues for consideration in the study setting
      and beyond, including conceptual and linguistic barriers to communicating
      effectively about research, the critical and complex role of communicators
      (fieldworkers and nurses) in consent procedures, features of research unit
      community relations which impact on these processes, and the special sensitivity
      of certain issues such as blood sampling. These themes and emerging
      recommendations are expected to be relevant to, and would benefit from,
      experiences and insights of researchers working elsewhere.

PMID- 15474209
TI  - Representations of SARS in the British newspapers.
AB  - In the Spring of 2003, there was a huge interest in the global news media
      following the emergence of a new infectious disease: severe acute respiratory
      syndrome (SARS). This study examines how this novel disease threat was depicted
      in the UK newspapers, using social representations theory and in particular
      existing work on social representations of HIV/AIDS and Ebola to analyse the
      meanings of the epidemic. It investigates the way that SARS was presented as a
      dangerous threat to the UK public, whilst almost immediately the threat was said
      to be 'contained' using the mechanism of 'othering': SARS was said to be unlikely
      to personally affect the UK reader because the Chinese were so different to 'us';
      so 'other'. In this sense, the SARS scare, despite the remarkable speed with
      which it was played out in the modern global news media, resonates with the
      meanings attributed to other epidemics of infectious diseases throughout history.
      Yet this study also highlights a number of differences in the social
      representations of SARS compared with earlier epidemics. In particular, this
      study examines the phenomena of 'emerging and re-emerging infectious diseases'
      over the past 30 or so years and suggests that these have impacted on the faith
      once widely held that Western biomedicine could 'conquer' infectious disease.

PMID- 15474210
TI  - Service users' strategies for managing risk in the volatile environment of an
      acute psychiatric ward.
AB  - Previous research shows that too often acute psychiatric inpatient care is
      neither safe nor therapeutic for patients. Earlier studies focused on promoting
      safety through good ward design, staff being able to anticipate and prevent
      violence, and use of medication. The current evidence base overwhelmingly
      reflects a staff perspective on risk management, and there is little evidence on
      how service users cope in this environment or about the strategies they employ to
      manage the risks they face or pose to others. This paper presents findings on
      this from two studies: (a) ethnographic research on three UK acute psychiatric
      wards, undertaken between 2000 and 2002, and (b) a content analysis of
      qualitative data from a 1999/2000 survey of psychiatric wards in England.
      Findings show that while some users perceive their ward to be comparatively safe-
      given the crisis they were in before being admitted--it is nonetheless a volatile
      environment in which risks are concentrated. Many risks, such as physical
      assault, are attributable to other patients. However, they are better understood
      as an outcome of the interplay between a range of interactional and contextual
      factors: for example, low staffing levels/minimal or poor surveillance may
      increase the risk of assault. Users were found to employ 10 strategies to manage
      risk on the ward, including actively avoiding risky situations/individuals,
      seeking staff protection, and getting discharged. Integral to these strategies
      are the risk assessments that patients make of one another. These findings shed
      light on how people cope while living in one of the most anxiety-inducing
      institutions of a 'risk management society'. Service users routinely take an
      active role in making a safe environment for themselves, in part because they
      cannot rely on staff to do this for them. Future clinical practice guidelines
      should consider how to harness what users are already doing to manage risk.

PMID- 15474212
TI  - Drug name confusion: evaluating the effectiveness of capital ("Tall Man") letters
      using eye movement data.
AB  - Medication errors commonly involve confusion between drug names that look or
      sound alike. One possible method of reducing these errors is to print sections of
      the names in "Tall Man" (capital) letters, in order to emphasise differences
      between similar products. This paper reports an eye-tracking experiment that
      evaluates this strategy. Participants had their eye movements monitored while
      they searched for a target product amongst an array of product packs. The target
      pack was replaced by a similar distractor in the array. Participants made fewer
      errors when the appearance of the names had been altered, that is, they were less
      likely to incorrectly identify a distractor as the target drug. This result was
      reflected in the eye movement data.

PMID- 15474211
TI  - Utilization of delivery services at the primary health care level in rural
      Vietnam.
AB  - The objective of this study is to investigate factors that influence the
      utilization of delivery services at the primary health care level in rural
      Vietnam. A quantitative survey was conducted amongst 200 women who had given
      birth within the past 3 months. Focus group discussions and in-depth-interviews
      were then undertaken using the attitudes--social influence--self-efficacy model
      to obtain complementary information on the delivery decision. The results show
      that client-perceived quality of services and socio-cultural and economic
      factors, rather than geographical access, can affect the utilization of delivery
      services. It is therefore important to improve the cost-efficiency of the health
      care network, and delivery services should be provided in a client-oriented
      manner taking into account economic, social and cultural factors.

PMID- 15474213
TI  - Migration, community context, and child immunization in Ethiopia.
AB  - This paper examines the relationship between parental migration status and child
      immunization in Southern Ethiopia, a region characterized by high mortality and
      morbidity. Using the 1997 Community and Family Survey and a multilevel modeling
      approach, we find that children born to rural-rural migrant mothers have
      significantly less chance of receiving full immunization coverage than children
      born to non-migrant mothers. The social mechanism that explains this huge
      disparity is that rural-rural migrant women have limited social networks in the
      host community. In addition, significant variation in receiving complete
      immunization is found by age of child (a likely period effect), mother's
      education, and distance to nearest health center. Marked child immunization
      differentials are also observed by ethnicity. The results from the multilevel
      analysis confirm the persistence of substantial community effects, even after
      controlling for a standard array of personal and household characteristics. Given
      the low levels of vaccination among children born to migrant women, health policy
      interventions and information campaigns might be effectively augmented to reach
      such migrant women and their children. Community and ethnic group effects suggest
      that further targeting of health activities could be efficient and effective.

PMID- 15474214
TI  - Policy formation in gamete donation and egg sharing in the UK--a critical
      appraisal.
AB  - This article considers two key policy documents concerning donor-assisted
      conception in the UK, The British Fertility Society's Recommendations for Good
      Practice on the Screening of Egg and Embryo Donors and the Human Fertilisation
      and Embryology Authority's Guidance for Egg Sharing Arrangements. It discusses
      both the process and the evidence used in formulating those sections of the
      documents which relate to donor anonymity. The paper concludes that psycho-social
      policy developments in assisted conception, such as those relating to donor
      anonymity, should be subjected to comparable levels of rigour and scrutiny to
      those that are applied in the formulation of medical and scientific policies.

PMID- 15474215
TI  - The sense of belonging to a neighbourhood: can it be measured and is it related
      to health and well being in older women?
AB  - This study investigates the sense of belonging to a neighbourhood among 9445
      women aged 73-78 years participating in the Australian Longitudinal Study on
      Women's Health. Thirteen items designed to measure sense of neighbourhood were
      included in the survey of the older women in 1999. Survey data provided a range
      of measures of demographic, social and health-related factors to assess scale
      construct validity. Factor analysis showed that seven of the items loaded on one
      factor that had good face validity and construct validity as a measure of the
      sense of neighbourhood. Two of the remaining items related to neighbourhood
      safety and comprised a factor. A better sense of neighbourhood was associated
      with better physical and mental health, lower stress, better social support and
      being physically active. Women who had lived longer at their present address had
      a better sense of belonging to their neighbourhood, as did women living in non
      urban areas and who were better able to manage on their income. Feeling safe in
      the neighbourhood was least likely in urban areas, increased in rural townships,
      and was most likely in rural and remote areas. Older women living alone felt less
      safe, as did women who were less able to manage on their income. This study has
      identified two sets of items that form valid measures of aspects of the social
      environment of older women, namely the sense of neighbourhood and feelings of
      safety. These findings make a contribution to our understanding of the
      relationship between feelings of belonging to a neighbourhood and health in older
      women.

PMID- 15474216
TI  - Elbow injuries in athletes.

PMID- 15474217
TI  - Elbow injuries in athletes.

PMID- 15474218
TI  - Elbow anatomy and structural biomechanics.
AB  - The elbow is a trochoginglymus joint with three articulations (the ulnohumeral,
      radiocapitellar, and proximal radioulnar joints) and two degrees of freedom
      (flexion/extension and pronation/supination). The congruity of the articulations
      as well as the medial and lateral collateral ligament complexes account for a
      majority of the stability of the joint. Muscles play a dynamic role in
      stabilizing the elbow. Understanding the anatomy and biomechanics of the elbow is
      essential to diagnosing and treating problems that develop in a patient's elbow.

PMID- 15474219
TI  - Biomechanics of the elbow in sports.
AB  - In throwing activities, the elbow is sometimes stressed to its biomechanical
      limits. In this article, forces, torques, angular velocities, and muscle activity
      about the elbow are reviewed for the baseball pitch, the football pass, the
      javelin throw, the windmill softball pitch, the tennis serve, and the golf swing.
      The elbow goes through rapid extension in baseball pitching (about 2400
      degrees/s) and rapid flexion in the javelin throw (about 1900 degrees/s). During
      baseball pitching, the elbow joint is subject to a valgus torque reaching 64 Nm,
      and requires proximal forces as high as 1000 N to prevent elbow distraction. The
      ulnar collateral ligament (UCL) rupture in baseball pitching, lateral
      epicondylitis in the tennis backhand, and other injury mechanisms are also
      discussed.

PMID- 15474220
TI  - Biomechanics and development of the elbow in the young throwing athlete.
AB  - This article reviews basic concepts in fundamental elbow biomechanics,
      particularly how they relate to the skeletally immature elbow in throwing
      athletes. Adult phases of throwing and the forces generated in each phase are
      compared with the developmental phases of throwing in children. The impact of
      elevated forces, poor mechanics, and poor coordination are emphasized as they
      relate to potential areas of injury in the skeletally immature. Finally, concepts
      in prevention focused on biomechanics are offered.

PMID- 15474221
TI  - Kinetic chain contributions to elbow function and dysfunction in sports.
AB  - The elbow functions in throwing and other athletic activities as a link in the
      kinetic chain of force development, regulation, and transfer. Efficient function,
      with maximal performance and minimal injury risk, requires optimum activation of
      all the link in the kinetic chain. Injury is often associated with alterations in
      force production or regulation capabilities in links that may be distant to the
      site of injury. Evaluation of injured athletes should include screening
      examinations for these areas, and treatment and conditioning should also include
      these areas.

PMID- 15474222
TI  - History and examination of the thrower's elbow.
AB  - Overhead throwing motion imparts enormous forces on the elbow. Repetitive near
      failure loads lead to chronic adaptive changes and occasionally acute injury to
      bone, ligaments, and the elbow's muscle-tendon complexes. Physicians treating the
      thrower must thoroughly understand the complex anatomy and function of the elbow
      joint and throwing biomechanics to diagnose and treat elbow pathology. Evaluation
      of elbow pain begins with a thorough, detailed throwing history, including
      symptom duration, location of pain, timing during phases of throwing motion, and
      associated symptoms. Physical examination should include inspection, range of
      motion, palpation, and specific tests to better define the pathology. A detailed
      history and physical examination often lead the astute clinician to the proper
      diagnosis and treatment without reliance on ancillary testing.

PMID- 15474223
TI  - Radiographic and special studies: recent advances in imaging of the elbow.
AB  - Advanced imaging techniques such as computed tomography, ultrasound, and magnetic
      resonance imaging provide clinically useful information by detecting and
      characterizing pathologic conditions of the elbow. The information provided by
      these techniques can help establish an anatomic diagnosis in a noninvasive
      fashion. A timely and accurate imaging diagnosis may be an important piece of the
      puzzle in a diagnostic workup that allows implementation of proper treatment and
      improved outcome. In this article, the authors focus on recent advances in
      diagnostic imaging of the elbow joint.

PMID- 15474224
TI  - Juvenile and adolescent elbow injuries in sports.
AB  - Elbow injuries in skeletally immature athletes continue to increase as juvenile
      and adolescent athletes participate in organized athletics at earlier ages and
      with greater intensity. Specialization in specific sports at younger ages has led
      to an increase in injuries related to repetitive microtrauma. As a result, the
      spectrum of injuries commonly seen in skeletally immature athletes has increased
      at a time when long-term outcomes and less invasive interventions with biologic
      principles are gaining greater attention. Optimal treatment of these injuries
      requires a knowledge of the complex developmental and radiographic anatomy, the
      pathophysiology and natural history, and the indications and expected outcomes
      for conservative and operative management.

PMID- 15474225
TI  - Elbow dislocations in adults and children.
AB  - Elbow dislocations occur following acute trauma to the elbow with associated
      disruption of the ligamentous complexes of the elbow. Observations regarding the
      details of ligament injuries are presented. Clinical presentation, examination,
      and investigations are included. Details of the management of dislocations
      including management of complex cases that require repair or reconstruction of
      the ligamentous complexes are included.

PMID- 15474226
TI  - PLRI: posterolateral rotatory instability of the elbow.
AB  - Recurrent and persistent instability of the elbow has long been a source of
      confusion and dismay for both patients and physicians. Early recognition after
      elbow injury and careful attention to soft tissue repair during lateral elbow
      surgery may diminish the incidence of this condition. Repair and reconstruction
      of the lateral ulnar collateral ligament (LUCL) now offers practical and often
      successful solutions for patients with posterolateral rotatory instability (PLRI)
      of the elbow.

PMID- 15474227
TI  - Ulnar collateral ligament injury in the overhead athlete: diagnosis and
      treatment.
AB  - The ulnar collateral ligament (UCL) is more commonly injured than previously
      suggested. Injury to this ligament can result in secondary symptoms and problems
      in other parts of the elbow, including the ulnar nerve, the flexor-pronator
      musculotendinous unit, the radiocapitellar joint, and the posterior compartment
      of the elbow, in addition to being a cause of loose bodies within the elbow. This
      article briefly reviews the anatomy, biomechanics, and pathophysiology of injury,
      in addition to discussing evaluation and treatment of the athlete with an injured
      UCL.

PMID- 15474228
TI  - Valgus extension overload syndrome and stress injury of the olecranon.
AB  - Basic science studies have improved our understanding of the pathomechanics for
      valgus extension overload and olecranon stress fractures. These disorders result
      from repetitive abutment of the olecranon into the olecranon fossa combined with
      valgus torques, resulting in impaction and shear along the posteromedial
      olecranon. The patient history and physical examination are similar for each
      disorder. Imaging studies including plain radiographs, computed tomography, MRI
      or bone scan may be necessary for accurate diagnosis. Clinical and basic science
      support mandatory and careful assessment of the medial collateral ligament when
      valgus extension overload is identified and limited debridement of the olecranon
      when surgery is indicated. For stress fractures that fail nonoperative
      management, treatment with internal fixation provides good results.

PMID- 15474229
TI  - Lateral epicondylitis.
AB  - Lateral epicondylitis is a diagnostic term that describes a pattern of pain and
      localized tenderness at the lateral epicondyle of the distal humerus. In this
      article, we discuss the pathology, clinical presentation, and treatment of this
      disorder. After a description of nonoperative treatment, we focus on the
      operative techniques for treating the disorder, and touch on postoperative care
      and results of treatment.

PMID- 15474230
TI  - Diagnosis and treatment of medial epicondylitis of the elbow.
AB  - Although limited literature exists on medial epicondylitis of the elbow, this
      disorder is an injury affecting many athletes at every level, especially throwing
      athletes. Care must be taken in diagnosing medial epicondylitis to distinguish it
      from other possible pathologies of the medial elbow, which may exist
      concurrently. The large majority of patients diagnosed with medial epicondylitis
      will respond to a well-structured, nonsurgical program; however, patients with
      persistent or recurring symptoms can be treated surgically, which yields high
      patient satisfaction and ultimately a reliable return to preinjury levels of
      activity.

PMID- 15474231
TI  - Biceps tendon and triceps tendon injuries.
AB  - Injuries to the biceps and triceps tendons about the elbow are relatively
      infrequent. Typically, they are traumatic events that occur as a result of a
      forceful eccentric contraction. Early recognition of these injuries and prompt
      intervention are the cornerstones to a successful outcome. Acute anatomic repair
      of complete injuries offers predictably good results. Conservative management, on
      the other hand, is typically reserved for partial injuries with little functional
      compromise, and for patients unfit for surgery. The challenges posed by chronic
      injuries can be addressed with a variety of surgical options. This article
      focuses on the timely identification and diagnosis of these injuries and specific
      indications and guidelines for their treatment.

PMID- 15474232
TI  - Nerve injuries in the throwing elbow.
AB  - The unique anatomy of the elbow combined with the angular velocity and stresses
      placed across this hinge joint while throwing can cause a large number of
      pathologic changes associated with nerves. Although the ulnar nerve is the most
      commonly injured, neuropathies are also seen with the branches of the median and
      radial nerves. These neuropathies are typically responsive to rest, activity
      modification, ice, splinting, and anti-inflammatories. A graduated return to
      throwing is then needed before returning to play. When conservative measures
      fail, surgical decompression is warranted, but results have been less than
      perfect.

PMID- 15474233
TI  - Miscellaneous conditions about the elbow in athletes.
AB  - This article reviews some of the conditions about the elbow in athletes or active
      individuals. The conditions discussed are synovial plica of elbow,
      radiocapitellar arthritis, congenital dislocation of the radial head, radio-ulnar
      synostosis, hemophilia and rheumatoid arthritis. In the past, people who had
      these conditions were instructed to avoid athletic activities; however, they are
      now being counseled to remain active and to try to exercise on a regular basis.

PMID- 15474236
TI  - The use of pessaries in vaginal prolapse.
AB  - Pessaries are frequently used in cases of vaginal prolapse. Many different type
      of pessaries have been used in the past and are still in use today. In general it
      is considered to be a safe and simple form of therapy but little is known on the
      success rate, the indications and the optimal management. We give an overview of
      the history, type, indications and complications of pessaries, and give
      guidelines for daily practice.

PMID- 15474234
TI  - Rehabilitation of the thrower's elbow.
AB  - The elbow joint is frequently injured in the overhead athlete, due to the large
      amount of forces in throwing. Injuries often occur due to repetitive microtrauma,
      especially in pitching. Rehabilitation following injury or surgery is vital to
      fully restore normal elbow function and return the athlete to competition as
      quickly and safely as possible. Elbow rehabilitation must follow a progressive
      and sequential order to ensure that healing tissues have not been compromised.
      Emphasis is on restoring full motion, muscular strength, and neuromuscular
      control, and gradually applying loads to healing tissue. This article provides an
      overview of a multiphased rehabilitation program for the thrower's elbow.
      Rehabilitation for specific nonoperative and postoperative pathologies often
      observed in the throwing athlete is also discussed.

PMID- 15474237
TI  - Risk of drug-induced congenital defects.
AB  - Defects attributable to drug therapy represent about 1% of congenital defects of
      known aetiology. This means that a precautionary attitude and correct use of
      drugs in fertile, and especially pregnant, women is a feasible form of
      prevention. Drugs currently in use with proven teratogenic effect number
      approximately 25, but new pharmaceutical drugs are constantly in preparation.
      Recognition of a drug-induced teratogenic effect is a complex procedure taking
      into account not only experimental animal data but also experience in humans.
      Considering that 40% of pregnancies are not planned, it follows that any drug
      with known or suspected teratogenic potential must be used only under strict
      medical control. Also, adequate knowledge on potential teratogenicity of a drug
      permits modification of therapy before conception. It goes without saying that
      any drug should be used during pregnancy only if it is essential, and it would be
      prudent to use only those where adequate information is provided and prior
      clinical experience is available. Teratology Information Services can assist both
      physicians and patients when any doubt exists.

PMID- 15474238
TI  - Delayed normalization of uterine artery Doppler waveforms is not a benign
      phenomenon.
AB  - OBJECTIVE: To evaluate the pregnancy outcome in patients with abnormal uterine
      artery Doppler flow velocity waveforms (FVW's) at 19-21 weeks, which were
      subsequently normal by 24-26 weeks, and to study the effect of low-dose aspirin
      on these waveforms. DESIGN: The study group consisted of 49 patients who had
      abnormal uterine artery flow velocity waveforms (FVW's) at 19-21 weeks. These
      women were initially commenced on 100 mg slow-release aspirin at 20 weeks, which
      was discontinued at the follow-up visit, after confirming normal uterine artery
      Doppler FVW. The control group consisted of 730 patients with normal uterine
      artery Doppler waveforms at 19-21 weeks. The main outcome measures were: small
      for gestational age (SGA) <10th centile, pre-eclampsia, placental abruption, and
      perinatal mortality rate (PMR). RESULTS: When compared with the control group,
      the study group had an increased risk of placental abruption (2% versus 0.27%, P
      = 0.05) 95% Confidence Intervals CI = 0.01-0.13), low birth weight (3087 versus
      3383 gm, P = 0.0003), SGA <10th centile (32.7% versus 11.9%, P </= 0.0001 , CI =
      0.14 -0.5), and PMR (2/49 versus 1/730, P < 0.0001 , CI = 0.003-0.37).
      CONCLUSIONS: These findings suggest that delayed normalisation of the uterine
      artery Doppler waveform is not a benign phenomenon. This subgroup of patients is
      at increased risk of pregnancy complications, in particular SGA and placental
      abruption. These patients could benefit from serial ultrasound scans in the third
      trimester to evaluate fetal growth and well-being. Aspirin does not appear to
      play a major part in modifying uterine artery blood flow.

PMID- 15474239
TI  - Major placenta praevia should not preclude out-patient management.
AB  - OBJECTIVE: To review current management of women with major and minor placenta
      praevia in view of the recommendations made in the RCOG guideline 2001. To assess
      whether out-patient care was detrimental to pregnancy outcome. STUDY DESIGN:
      Retrospective observational study at the Simpson Memorial Maternity Pavilion,
      Edinburgh (a tertiary referral centre). One hundred and sixty-one women with
      major and minor placenta praevia between 1994 and 2000 were separated into those
      who experienced bleeding (antepartum haemorrhage (APH)) and those who had no
      bleeding during pregnancy (non-APH). Statistical analysis was carried out using
      SPSS. RESULTS: There were 129 women (80%) in the APH group. Forty-three were out
      patients at the time of delivery and 63% had a major degree of praevia. Thirty
      two women were in the non-APH group. Sixty-eight were managed as out-patients and
      50% had a major degree of praevia. Women with a major degree of praevia were not
      significantly more likely to experience bleeding. Women with APH were
      significantly more likely to be delivered early, by emergency caesarean section
      (C/S), of lower birthweight babies who required neonatal admission than the non
      APH group. CONCLUSION: There is a place for out-patient management of women with
      placenta praevia. Caution is required with increasing number of bleeds but not
      degree of praevia.

PMID- 15474240
TI  - Women's attitude toward analgesia during labor--a comparison between 1995 and
      2001.
AB  - OBJECTIVE: To compare the attitude of gravid women towards analgesia during labor
      in 1995 and 2001, in Israel. METHOD: Women in the third trimester of pregnancy
      were asked to complete an antepartum questionnaire regarding the mode of
      analgesia they preferred during their labor. The questionnaire was distributed
      twice, once in 1995 and again in 2001, in order to study changing attitudes.
      RESULTS: Study participants included 114 women in 1995 and 125 in 2001. There
      were no differences between the groups in maternal age, gestational age, gravity,
      parity, or level of education. In 1995, 57% of the women were interested in
      having epidural analgesia during labor, compared to 66% in 2001 (P < 0.001). The
      preference for opioids decreased from 31.5% in 1995 to 18.5% in 2001 (P < 0.001).
      In 1995, none of the women questioned opted for avoiding all kinds of analgesia,
      whereas in 2001, 8% did so. CONCLUSION: Women's attitudes to analgesia during
      labor have changed over the last 6 years. Epidural block has become very popular,
      while opioids use lost its popularity; at the same time, there has been an
      increase in the number of women who prefer to avoid all kinds of analgesia during
      labor.

PMID- 15474241
TI  - Ultrasonographic cervical length measurement is not a better predictor of preterm
      delivery than digital examination in a population of patients with idiopathic
      preterm labor.
AB  - OBJECTIVE: To compare digital and ultrasonographic cervical examination for the
      prediction of preterm delivery in patients hospitalized for preterm labor. STUDY
      DESIGN: Fifty-nine patients were included. The Bishop score was evaluated upon
      admission, weeks gestational age. Ultrasonographic measurement of cervical length
      was done within 24h after entry. Delivery before 37 weeks gestational age was the
      primary endpoint. Attending obstetricians were blinded to the results of
      echography. RESULTS: Preterm delivery rate was 39% (23/59). The risk of preterm
      delivery was significantly increased when the Bishop score was greater than or
      equal to 6 (OR = 4.45 [1.41-14.01]) or when ultrasonographic cervical length was
      less than or equal to 27 mm (OR = 4.04 [1.32-12.3]), but digital examination was
      the only independent risk factor in multivariate analysis. Sensitivity,
      specificity, positive and negative predictive value for digital examination and
      ultrasonography were respectively 74, 61, 55 and 79%, 70, 64, 55 and 77%.
      Combination of digital examination and ultrasonography did not yield better
      results. CONCLUSION: In our series, prediction of preterm delivery was not
      improved by ultrasonography compared to digital examination. The size of the
      cervical shift observed in most patients hospitalized for preterm labor may
      render ultrasonography less relevant in identifying patients anticipated to
      deliver prematurely.

PMID- 15474242
TI  - Circulating levels of inhibin A, inhibin B and activin A in normal and
      intrauterine growth restricted (IUGR) fetuses.
AB  - OBJECTIVE: To evaluate the relationships between circulating levels of inhibin A,
      inhibin B and activin A, and sex, gestational age and gonadotropins in normal and
      pathological fetuses. STUDY DESIGN: The study included 31 normal fetuses and 12
      affected with intrauterine growth restriction (IUGR) of gestational age ranging
      20-40 weeks. RESULTS: No gender difference in inhibin A and activin A levels were
      observed. Inhibin B levels were significantly higher in males than in females (P
      < 0.05). Fetuses with the highest levels of inhibin A and B were found in the
      IUGR group that also showed activin A levels significantly higher than normal. No
      correlations were observed between inhibin A, inhibin B, activin A and both
      gonadotropins. CONCLUSION: Plasma inhibin A, inhibin B and activin A are
      detectable in both genders during intrauterine life. The different gender pattern
      of inhibin B suggests that inhibin B may contribute to the assessment of the
      hypothalamic-pituitary-gonadal set-point at least in males.

PMID- 15474243
TI  - Inherited risk of thrombosis of the fetus and intrauterine fetal death.
AB  - OBJECTIVE: To test the hypothesis that abnormal placentation resulting in
      intrauterine fetal death (IUFD) is associated with coagulation abnormalities in
      the fetus. STUDY DESIGN: We analyzed fetal DNA from umbilical cords from 139
      pregnancies complicated by intrauterine fetal death during 1994-1998 (cases).
      Fetal DNA was tested for the presence of factor V Leiden and prothrombin G20210A
      mutations. The prevalence of these thrombophilic mutations among cases were
      compared with the prevalence in a historic control group. RESULTS: Overall, a
      higher prevalence of fetal genetic risk factors was found in cases (9.8%) as
      compared to fetuses born from an uncomplicated pregnancy (2%, odds ratio 4.8, 95%
      CI 1.1-22). Second trimester intrauterine fetal death occurred more frequently in
      cases with the factor V Leiden mutation as compared with the control group (8/64
      versus 0/92). For intrauterine fetal death and factor V Leiden a high risk was
      found concerning abruption placentae (odds ratio 7.6, 95% CI 1.5-37). CONCLUSION:
      The prevalence of fetal genetic risk factors associated with an increased risk
      for thrombosis was higher in pregnancies complicated by intrauterine fetal death
      suggesting an important role of abnormal coagulation in placentation.

PMID- 15474244
TI  - Genetic aspects of human male infertility: the frequency of chromosomal
      abnormalities and Y chromosome microdeletions in severe male factor infertility.
AB  - OBJECTIVE: The main purpose of this study is to detect the frequency and type of
      both chromosomal abnormalities and Y chromosome microdeletions in patients with
      severe male factor infertility and fertile control subjects. The association
      between the genetic abnormality and clinical parameters was also evaluated.
      METHODS: This study was carried out in 208 infertile and 20 fertile men. Results
      of 208 patients, 119 had non-obstructive azoospermia and 89 had severe
      oligoasthenoteratozoospermia (OAT). Seventeen out of 119 (14.3%) azoospermic
      patients and two out of 89 (2.2%) patients with OAT had Y chromosome
      microdeletions. In total, 19 cases with deletions were detected in 208 infertile
      men, with a frequency of 9.1%. The AZFc locus, mainly DAZ gene cluster was the
      most frequently deleted region. Five other cases with azoospermia (4.2%) and two
      cases with OAT (2.2%) had a chromosomal abnormality, with a total number of seven
      (3.4%). Including Y chromosome deletions and structural chromosome abnormalities,
      the rate of genetic abnormalities was 12.5% (26/208) in our patients. On the
      other hand, 20 men with proven fertility and fathers of five cases with
      microdeletions were genetically normal. Y chromosome deletions and chromosomal
      abnormalities were associated with various histological alterations in testis.
      Sertoli cell-only (SCO) syndrome and maturation arrest predominated in these
      cases, whereas hypospermatogenesis occurred more frequently in genetically normal
      patients. CONCLUSION: Various chromosomal abnormalities and deletions of Y
      chromosome can cause spermatogenic breakdown resulting in chromosomally derived
      infertility. All these findings strongly support the recommendation of genetic
      screening of infertile patients.

PMID- 15474245
TI  - Hormone replacement influences homocysteine levels in the methionine-loading
      test: a randomized placebo controlled trial in postmenopausal women.
AB  - OBJECTIVE: To investigate the mechanism by which exogenous oestrogen influences
      the homocysteine metabolism in postmenopausal women. STUDY DESIGN: A randomized
      placebo controlled trial in which a methionine-loading test was performed, in 25
      healthy postmenopausal women, before and after a 12-week oral treatment with
      placebo or daily 4 mg 17beta-estradiol with (HRT) or without (ERT) 10 mg
      dydrogesterone. Fasting and post-load homocysteine as well as Vitamins B(6),
      B(12) and folate were determined. RESULTS: In both treatment groups a significant
      12% decrease in fasting homocysteine was observed. This decrease was accompanied
      by a post-load homocysteine increase of more than 20%. Vitamin B(6) values were
      decreased by more than 25%. CONCLUSION: The hormone therapy induced lowering of
      fasting homocysteine and Vitamin B(6) levels and an increase in post-load
      homocysteine, supporting the hypothesis that homocysteine-methionine metabolism
      is modulated by hormone therapy in postmenopausal women.

PMID- 15474246
TI  - One, two or three: how many directions are useful in transvaginal ultrasound
      measurement of ovarian follicles?
AB  - OBJECTIVE: To investigate whether it is necessary to measure an ovarian follicle
      in three directions using transvaginal ultrasonography. METHODS: In 36 healthy
      female volunteers transvaginal ultrasonography was performed every other day
      during a spontaneous menstrual cycle. The diameter of the largest follicle in
      each ovary was measured in two directions in the sagittal plane, and in two
      directions in the coronal plane. In total, 304 follicular measurements were
      performed. The largest follicular diameter was compared to the mean diameter of
      two and three directions, respectively. The mean diameter of two directions was
      compared to that of three directions. RESULTS: The mean difference between
      measurement in one and two directions was 1.2 mm (standard deviation (S.D.) = 1.1
      mm), between measurement in one and three directions 1.2 mm (S.D. = 1.0 mm), and
      between measurement in two and three directions -0.03 mm (S.D. = 0.3 mm). The
      mean difference and the standard deviation of the difference increased with the
      follicular diameter. CONCLUSIONS: In non-stimulated menstrual cycles, follicle
      measurement in only one direction is less accurate than measurement in two and
      three directions, and may result in clinically relevant differences. However,
      measurement in three directions gives no additional information compared to
      measurement in two directions.

PMID- 15474247
TI  - The effect of inducible nitric oxide synthase on postoperative adhesion formation
      in rats.
AB  - OBJECTIVE: To evaluate the effect of iNOS on adhesion formation and to assess
      whether inhibition of iNOS expression affected adhesion formation according to
      adhesion maturation days. STUDY DESIGN: Forty Wistar Albino rats were subjected
      to standardized lesion by cecal abrasion and parietal peritoneal defect and were
      randomly divided into four groups. Group I (control) received no treatment;
      groups II-IV received N-acetyl-cystein (NAC) 15 mg/100 g per day intramuscularly
      on days 4-14, 0-14 and 0-3, respectively, after surgery. On the postoperative
      14th day adhesion score, tissue iNOS expression, inflammatory cell reaction (ICR)
      and tissue fibrosis score were determined. RESULTS: Inflammation score of groups
      I and II was lower than that of groups III and IV (P < 0.05). Adhesion scores and
      tissue fibrosis of group II were significantly lower than that of the other
      groups (P < 0.001). CONCLUSION: iNOS inhibition during the first 3 days
      postoperatively caused a delay in the resolution of inflammatory cell reaction.
      On the other hand, when inhibited after the first 3 days, adhesion formation and
      fibrosis were reduced both clinically and histopathologically.

PMID- 15474248
TI  - Efficacy and safety of vitamin C vaginal tablets in the treatment of non-specific
      vaginitis. A randomised, double blind, placebo-controlled study.
AB  - METHODS: This was a randomised, double-blind, placebo-controlled study to
      evaluate the efficacy and safety of Vitamin C vaginal tablets (250 mg) given once
      a day in patients suffering from non-specific vaginitis. The total length of the
      study was 20 days, including a treatment phase of 6 days. The primary end-point
      was the presence in the two groups of non-specific vaginitis 1 and 2 weeks after
      the end of treatment, as assessed by at least 3 out of the 4 characteristic
      symptoms: discharge, fishy odour, vaginal pH >/= 4.7, and presence of clue cells.
      Secondary end-points were the individual symptoms and signs, above reported, and
      pruritus, fever, superinfections, microscopic findings on vaginal smear, and
      colposcopy. PATIENTS: One hundred female patients aged 18 years or older and
      suffering from non-specific vaginitis were included in the study after giving
      their informed consent. Fifty were randomised to the active treatment and 50 to
      placebo. Seven patients, three in the Vitamin C group and four in the placebo
      group, were lost to follow-up and did not complete the treatment period. Two
      patients in the active group showed protocol deviations (age under 18 years and
      HIV-positive, respectively). The two groups resulted comparable for demographics,
      history and baseline clinical picture. RESULTS: A cluster analysis of the four
      main symptoms showed a statistically significant difference between the active
      group and the placebo group; significantly more patients were still affected by
      non-specific vaginitis after placebo (35.7%) compared to patients treated with
      Vitamin C tablets (14.0%). The meaningful secondary variable, referring to the
      microscopic examination of vaginal smear, supported the trend for efficacy in the
      Vitamin C treated group. The clue cells disappeared in 79% of patients treated
      with the drug and in 53% of patients on placebo. Similarly, bacteria disappeared
      in 77 and 54%, respectively, while lactobacilli reappeared in 79.1 and 53.3%,
      respectively. Vaginal pH values decreased significantly in both groups, but the
      frequency rate of subjects with pH >/= 4.7, as measured 1 week after the drug
      discontinuation, was significantly lesser in the Vitamin C group (16.3%) than in
      the placebo group (38.6%). Adverse events occurred in four patients, two on
      placebo (pruritus, cystitis) and two on Vitamin C (two candidiasis).

PMID- 15474249
TI  - Novel insight into the vaginal microflora in postmenopausal women under hormone
      replacement therapy as analyzed by PCR-denaturing gradient gel electrophoresis.
AB  - OBJECTIVES: A study was conducted to use new molecular technologies to identify
      the vaginal bacterial species of postmenopausal women under oral estrogen therapy
      (Premarin-conjugated equine estrogen, CEE). STUDY DESIGN: Nineteen postmenopausal
      women under CEE treatment were recruited and their vaginal flora were analyzed
      during 3 months, using polymerase chain reaction in combination with denaturing
      gradient gel electrophoresis (DGGE) and sequencing of DNA fragments. RESULTS:
      Sixty-eight percent of the women presented with a 'Normal' Nugent score at the
      first sampling time (d0). All the subjects had bacterial species detected in
      their vaginal flora. Lactobacillus species were detected in all samples.
      Moreover, 53% of the women had lactobacilli exclusively at d0. Two Lactobacillus
      species were dominant, and were recovered from the majority of samples (L. iners
      and L. crispatus). Forty-four percent of the samples also contained other
      bacterial species, which were potential urogenital pathogens. Candida albicans
      was detected in 26% of the subjects. The vaginal flora of the women under CEE
      treatment were different from that of postmenopausal women not receiving hormone
      therapy, but very similar to premenopausal women. CONCLUSIONS: The present study
      indicates that one benefit from hormone replacement therapy (HRT) is the
      restoration of a lactobacilli vaginal flora associated with a protective effect
      against urogenital infections.

PMID- 15474250
TI  - A retrospective multicentre study comparing myomectomy by laparoscopy and
      laparotomy in current surgical practice. What are the best patient selection
      criteria?
AB  - OBJECTIVE: To determine the differences in myoma characteristics before
      laparoscopic myomectomy (LM) and abdominal myomectomy (AM) and to compare
      outcomes in current practice. STUDY DESIGN: We analysed retrospectively the data
      for 126 LMs and 176 AMs performed between January 1996 and January 2000 in 11
      centres. Myomas were examined by transvaginal B-mode, colour and pulsed energy
      Doppler ultrasonography. The following data were collated: (i) pre-operative:
      myoma size, number, type and location and medical treatment, (ii) per-operative:
      operator, blood loss, surgical procedure and operative time, and (iii) post
      operative: myoma weight and number, haemoglobin decrease, complications and
      length of hospital stay. RESULTS: Compared to women undergoing LM, women
      undergoing AM had more myomas that were larger and that were generally
      interstitial and anterior. More of them received GnRH analogues. Excised myomas
      weighed four times more, the decrease in haemoglobin was greater (1g/dl), fever
      was more frequent, and nine patients needed transfusions (compared to none for
      LM). There were 37 laparoconversions (29%) after LM. The conversion rate was high
      for inexperienced surgeons. Length of hospital stay was reduced by half for LM
      (without laparoconversion). Recurrence rate at 2 years was 2.5% for LM versus
      3.6% for AM (P = 0.506). CONCLUSION: Pre-operative evaluation by ultrasound is
      essential to establish myoma number, size, type and location in order to choose
      the most appropriate surgical procedure.

PMID- 15474251
TI  - Pre- and post-treatment patterns of human chorionic gonadotropin for early
      detection of persistence after a single dose of methotrexate for ectopic
      pregnancy.
AB  - OBJECTIVE: Given the great variability of human chorionic gonadotropin (HCG)
      levels after a single dose of methotrexate (MTX) for ectopic pregnancy, it
      remains complicated to identify cases undergoing persistence until a week from
      treatment. We evaluated whether pre-treatment patterns of HCG levels could be
      useful for an earlier detection of persistent trophoblast. STUDY DESIGN: A
      retrospective study on 62 patients treated by a systemic single dose of
      methotrexate (50 mg/m(2)) for an ectopic pregnancy. Samples for HCG detection
      were obtained on days -2 and 0 before the therapy, on days +3, +7 and then weekly
      until values were undetectable. Patients were divided into three groups: Group U
      (up, meaning "increasing") and Group D (down, meaning "decreasing") when HCG
      levels on day 0 were respectively higher or lower than day -2 level of more than
      20% and Group P (plateau) when the difference between day -2 HCG level and the
      level on day 0 was less than 20%. RESULTS: All the patients of Group D underwent
      a complete resolution, with a percentage of 33.3% of cases who underwent an
      initial rise of HCG levels on day +3. The percentage of cases undergoing an
      initial rise of HCG levels in Group U patients was significantly higher than in
      Group P patients (60.0% versus 28.6%), but the resolution rate resulted similar
      in the two groups. For patients of Group P, an increase of HCG levels on day +3
      was significantly correlated to the failure of the therapy. Indeed, comparing the
      cases with an immediate increase of HCG levels to the cases with immediate
      decrease of HCG levels on day +3, the persistence rate was 80% for the former and
      12% for the latter (P < 0.0001). CONCLUSION: An initial rise of HCG levels after
      the therapy does not seem to have a clinical relevance in Group D and Group U
      patients, it well correlates to trophoblastic persistence in Group P patients.

PMID- 15474252
TI  - A score for measurement of the role of social vulnerability in decisions on
      abortion.
AB  - OBJECTIVE: To devise a score allowing a better measure of the role of social
      vulnerability (SV) in a woman's attitude toward abortion. STUDY DESIGN:
      Consecutive sampling and semi-structured personal interviewing of 2641 women
      requesting legal termination of pregnancy from 1994 to 2001 in the county of
      Roanne, France. RESULTS: SV was estimated from each woman's situation with
      reference to work, family composition, marital status, health insurance status
      and characteristics of neighbourhood of residence. It was correlated with the
      income and home ownership situation. With a high SV level taken as reference, the
      relative risks (RR) of severe, moderate, and low SVP, respectively, were equal to
      3.3 (1.8-6.1), 4.6 (2.5-8.6) and 7.2 (3.9-13.1) in women under 18.5 years of age;
      1.2 (1.0-1.5), 2 (1.4-2.8), and 2.1 (1.4-3.2) from 18.5 to 19 years of age; 0.7
      (0.6-0.8), 0.6 (0.5-0.8) and 0.4 (0.3-0.5) in those aged 19-28; and 0.9 (0.9-1),
      0.7 (0.6-0.8) and 0.71 (0.6-0.8) in those over 28. The use of different basic
      hypotheses (cumulative time of pregnancy in women's life, withdrawal or
      restarting of the clock after each event in the case of recurrence) resulted in
      slight modification of the age cut-off points and the amplitude of RR also
      differed, but their order relative to SV categories was unchanged. CONCLUSIONS:
      At the individual level knowledge of SV allowed a good estimate of a woman's
      attitude to an unwanted pregnancy, and SV must be taken into consideration when
      future actions are planned.

PMID- 15474253
TI  - A monozygotic twin pregnancy discordant for acardia and X-inactivation pattern.
AB  - Monochorionic, diamniotic twins discordant for acardia are reported. A 775 g
      acardius was dead, generally hydropic and severely malformed, while the other
      twin with a weight of 1314 g was phenotypically normal. Both twins had a normal
      46 XX karyotype. Genotyping at 24 autosomal polymorphic loci revealed that the
      twins were identical (monozygotic) and ruled out uniparental disomy for
      chromosome 2. X-inactivation studies showed a skewed pattern in the acardiac twin
      and a normal random pattern in the co-twin, suggesting that the underdevelopment
      of the acardiac twin may have reflected the small number of original cells that
      were separated from the inner cell mass.

PMID- 15474254
TI  - Complex genital malformation: ectopic ureter ending in a supposed mesonephric
      duct in a woman with renal agenesis and ipsilateral blind hemivagina.
AB  - We present a clinical case of a patient with left renal agenesis and ipsilateral
      blind hemivagina who also had one or more atretic ectopic ureters opening into
      supposed mesonephric duct, which in turn opened into, or joined onto, the
      ipsilateral hemicervix, continuing with the blind hemivagina. The diagram of this
      complex genitourinary malformation would strongly support our hypothesis of the
      embryology of the human vagina as deriving from the Wolffian ducts and the
      Mullerian tubercle.

PMID- 15474255
TI  - New onset seizures in pregnancy caused by an unexpected neurologic disorder.
AB  - Seizures in pregnancy are a life-threatening emergency that continues to be a
      major cause of serious maternal and fetal morbidity and mortality. We report a
      rare cause of new onset of seizures in pregnancy: hydrocephalus caused by
      aqueductal stenosis. The differential diagnosis of seizures in pregnancy is
      discussed in detail.

PMID- 15474257
TI  - Huge clear cell carcinoma of the cervix in teenager not associated with
      diethylstilbestrol: a brief case report.

PMID- 15474256
TI  - A case of ovarian adenosarcoma with a heterologous rhabdomyosarcoma component: a
      brief case report.

PMID- 15474258
TI  - Heterotopic triplet pregnancy with laparoscopic resection of the ruptured tube at
      10 weeks of gestation.

PMID- 15474259
TI  - Ruptured splenic artery aneurysm during pregnancy with maternal death and
      premature infant survival.

PMID- 15474261
TI  - EAU 2004 guidelines on assessment, therapy and follow-up of men with lower
      urinary tract symptoms suggestive of benign prostatic obstruction (BPH
      guidelines).
AB  - OBJECTIVE: To provide the first update of the EAU guidelines on assessment,
      therapy and follow-up of men with lower urinary tract symptoms (LUTS) suggestive
      of benign prostatic obstruction (BPO). METHODS: A systematic literature review
      was conducted based on the results of a MEDLINE search concentrating on the years
      1999-2003. In combination with expert opinions recommendations were made on the
      usefulness of diagnostic tests, therapeutic options and follow-up. RESULTS:
      During initial assessment the following tests are recommended: medical history,
      physical examination including digital-rectal examination, International Prostate
      Symptom Score, urinalysis, serum creatinine and prostate specific antigen
      measurement, uroflowmetry and post-void residual volume. All other tests are
      optional or not recommended. Aim of treatment is to improve LUTS and quality of
      life and to prevent severe BPE-related complications. Development of a 5alpha
      reductase type I and II inhibitor and the data of the MTOPS trial providing
      scientific evidence for a combination therapy were the most significant
      innovations since the first version. Finally a more detailed knowledge on the
      natural history with identification of several risk factors for progression is
      the basis for a risk-profile orientated (preventive) therapy. CONCLUSIONS:
      Updated recommendations for assessment, treatment, and follow-up of patients with
      LUTS due to BPO are presented.

PMID- 15474262
TI  - EAU guidelines on ejaculatory dysfunction.

PMID- 15474263
TI  - Neoplasm staging and organ-confined renal cell carcinoma: a systematic review.
AB  - OBJECTIVES: Several TNM staging system editions were published over the years for
      renal cell carcinoma (RCC). Using a search strategy similar to the one used by
      the TNM process Subcommittee for "literature watch", we searched MEDLINE with the
      intent to critically analyze literature concerning the different TNM editions and
      the data regarding the optimal breakpoints to substratify localized RCC. MATERIAL
      AND METHODS: The electronic search was conducted as follows: "Neoplasm staging"
      [MeSH] AND "Carcinoma, Renal Cell" [MeSH]. At the end of a process of abstract
      analysis performed separately by three of the authors, 34 papers were included in
      the systematic review. RESULTS: All the 34 selected papers were retrospective
      studies. According to the 1987 version of TNM classification, no paper showed
      statistically significant cancer-specific survival probability differences
      between stage I and stage II RCC. According to the 1997 TNM version, the results
      were controversial. While a few papers found significantly different cancer
      specific survival rates between stage I and stage II RCC, several others failed
      to do so. With the aim to stratify patients with localized RCC, most of the
      papers proposed an ideal breakpoint ranging from 4.5 to 5.5 cm. CONCLUSION: This
      literature review highlighted that a correct definition of the staging of organ
      confined RCC was far from being achieved and provided an appropriate synopsis of
      the available data for further update of the TNM staging system.

PMID- 15474264
TI  - European collaborative group on prostate brachytherapy: preliminary report in
      1175 patients.
AB  - OBJECTIVE: To establish a multi-centre database of a large number of patients
      treated with brachytherapy across Europe. METHODS: A total of 1175 patient files
      were registered in the database and the completeness of the data on these
      patients resulted in the majority being included in the analysis. RESULTS: The
      database of patients treated with brachytherapy across Europe indicates that
      optimal patient selection for this procedure has been made, both in terms of
      outcome and side-effects, which will be subject of future analyses. This should
      enable refinement of the treatment choice and administration as well as provide
      useful guidance to other centres that want to establish this procedure for their
      patients. It will also set the ground for prospective studies. CONCLUSIONS: The
      established database indicates that brachytherapy as a treatment option for
      prostate cancer is well established in many centres.

PMID- 15474265
TI  - Preoperative neural network using combined magnetic resonance imaging variables,
      prostate specific antigen, and Gleason score to predict prostate cancer
      recurrence after radical prostatectomy.
AB  - OBJECTIVE: An artificial neural network analysis (ANNA) was developed to predict
      the biochemical recurrence more effectively than regression models based on the
      combined use of pelvic coil magnetic resonance imaging (pMRI), prostate specific
      antigen (PSA) and biopsy Gleason score in patients with clinically organ-confined
      prostate cancer after radical prostatectomy (RP). METHODS: Two-hundred-and-ten
      patients undergoing retropubic RP with pelvic lymphadenectomy were evaluated.
      Predictive study variables included clinical TNM classification, preoperative
      serum PSA, biopsy Gleason score, transrectal ultrasound (TRUS) findings, and pMRI
      findings. The predicted result was a biochemical failure (PSA >or=0.1 ng/ml).
      Using a five-way cross-validation method, the predicted ability of ANNA for a
      validation set of 200 randomly selected patients was compared with those of Cox
      regression analysis and "Kattan nomogram" by area under the receiver operating
      characteristic curve (AUC) analysis. RESULTS: Seventy-three patients (35%) failed
      at median follow-up of 61 (mean: 60, range: 2-94) months. Using similar input
      variables, the AUC of ANNA (0.765, 95% Confidence Interval [CI]: 0.704-0.825) was
      comparable (p > 0.05) to those for Cox regression (0.738, 95%CI: 0.691-0.819) and
      Kattan nomogram (0.728, 95%CI: 0.644-0.819). Contrarily, adding the pMRI
      findings, the ANNA is significantly (p < 0.05) superior to any other predictive
      model (0.897, 95%CI: 0.841-0.977). The Gleason score represented the most
      influential predictor (relative weight: 2.4) of PSA recurrence, followed by pMRI
      (2.2), and PSA (2.0). CONCLUSION: ANNA is superior to regression models to
      predict accurately biochemical recurrence. The relative importance of pMRI and
      the utility of ANNA to predict the PSA failure in patients referred for RP must
      be confirmed in further trials.

PMID- 15474266
TI  - Computed tomographic virtual cystoscopy for the detection of urinary bladder
      neoplasms.
AB  - OBJECTIVE: To evaluate the role of computed tomographic virtual cystoscopy (CTVC)
      in the detection of bladder neoplasms and to compare CTVC at conventional and
      reduced milliAmperes-second (mAs) settings. METHODS: Twenty-four patients with
      known bladder neoplasms from previous conventional cystoscopy were examined with
      CTVC. The urinary bladder was insufflated with room air and helical CT data were
      obtained. Virtual images were created using volume rendering algorithms. In eight
      patients we used both regular (240) and reduced (70) mAs values. The lesions were
      recorded on transverse tomographic slices and virtual images and compared with
      conventional cystoscopy, operative and pathology results. RESULTS: All bladder
      lesions (30) seen on conventional cystoscopy were demonstrated with CTVC. Two
      lesions detected on imaging studies and subsequently found at operation were not
      seen on conventional cystoscopy. In a third case of a neobladder, conventional
      cystoscopy was impossible due to neoplastic involvement of the penis. In all
      cases the lesions were equally conspicuous with conventional and low mAs values.
      CONCLUSIONS: Computed tomographic virtual cystoscopy is a minimally invasive
      technique that can provide comprehensive information about urinary bladder
      tumors. Furthermore, low mAs studies are equally effective for the examination of
      such patients.

PMID- 15474267
TI  - The Vista system: a new bipolar resection device for endourological procedures:
      comparison with conventional resectoscope.
AB  - OBJECTIVE: Conventional transurethral resection of the prostate (TURP) uses a
      monopolar electrocautery system in which the current passes from the active
      electrode through the patient's body towards the return plate and may cause
      distant negative effects. In this study a new developed resection device, the
      Vista system, using a bipolar electrocautery system and 0.9% sodium chloride
      solution for irrigation, was evaluated in an ex-vivo model. METHODS: The modified
      model of the isolated blood perfused kidney was used to determine cutting
      qualities, ablation rate, blood loss and coagulation depth of the bipolar
      resectoscope. After ablating the renal tissue of a perfused kidney in a surface
      area, blood loss was semiquantitatively determined. Afterwards samples were taken
      and processed for histological evaluation of the coagulation depth. We compared
      the new bipolar resection device against a conventional monopolar resectoscope.
      RESULTS: We found good cutting qualities of the bipolar resectoscope although it
      is more difficult to start a cut. The ablation rate is determined by the width of
      the electrode and is similar to the standard device (30 cm(2)/min). The bleeding
      is reduced with increasing output powers (26.13 +/- 6.15 g/min (level 5); 20.49
      +/- 5,47 g/min (level 6); 13.16 +/- 5,47 g/min (level 7); 10.43 +/- 4.76 g/min
      (level 8) and lower compared to a conventional monopolar resectoscope (17.08 +/-
      4.47 g/min). The coagulation depth increases with higher output powers but is
      reduced compared to the standard device (118 +/- 22 microm (level 5); 121 +/- 23
      microm (level 6); 141 +/- 62 microm (level 7); 163 +/- 30 microm (level 8) versus
      287 +/- 57 (monopolar resectoscope)). CONCLUSION: Our results with the bipolar
      resection device for TURP suggest that it may offer an alternative to
      conventional TURP. As active and the return electrode are placed on the
      resectoscope, high current densities are achieved locally and complications
      caused by distant negative effects of the current are theoretically reduced in
      vivo. Furthermore the risk of TUR syndrome is theoretically eliminated by using
      physiological sodium chloride solution for irrigation. To prove the clinical
      significance of our ex-vivo findings, clinical studies including large numbers of
      patients have to be performed.

PMID- 15474268
TI  - Health-related quality-of-life following modified ureterosigmoidostomy (Mainz
      Pouch II) as continent urinary diversion.
AB  - INTRODUCTION AND OBJECTIVES: The purpose of this study was to estimate the health
      related quality of life (HRQoL) following modified ureterosigmoidostomy (Mainz
      Pouch II) urinary diversion. MATERIALS AND METHODS: Between March 1995 and
      February 2003 the procedure was performed in 83 patients (67 male and 16 female,
      median age 62 years, range 2-78 years) at the Departments of Urology in Bonn,
      Germany, and Pesaro, Italy. Patients were asked during follow-up to complete a
      validated, cancer-specific quality of life questionnaire, namely the EORTC QLQ C
      30 Version 3. Forty-one patients (29 male, 12 female) completed the QLQ C-30.
      Twenty-eight patients were dead at the time of the study and 14 patients were
      lost to follow-up. A non-validated questionnaire was answered by 31 patients
      (75%) of the Bonn series to determine specific urinary diversion items. Mean
      follow-up time was 24.4 months (6 to 84 months). RESULTS: No statistically
      significant differences (p < 0.05) in functional and symptom scales or global
      health status were detected between males and females. All scales but diarrhea
      showed good results and the outcome was comparable to health-related quality of
      life in a reference population of Germany. Continence rate was 100% at daytime;
      all but one patient had to get up for urination at night. About one third of the
      patients have to urinate more than six times during the day and more than three
      times during the night. Sixty-three percent of the patients in the Bonn series
      were able to distinguish between stool and urine. CONCLUSION: The Mainz Pouch II
      serves as a satisfying continent urinary diversion for both sexes in selected
      patients in terms of quality of life. Patients seem to adapt to their
      "individual" form of urinary diversion. In terms of continence modified
      ureterosigmoidostomy can lead to daytime continence rate of 100%. The relatively
      high voiding frequency during night-time was not felt to be disturbing by the
      patients and demonstrates the adaptability of the patients.

PMID- 15474269
TI  - Antireflux uretero-intestinal anastomosis--flap-and-trough technique--applicable
      to ileum: early clinical experience.
AB  - OBJECTIVE: To report our functional results of the "flap-and-trough" (FT)
      antireflux uretero-intestinal anastomosis (UIA) applied to various forms of
      urinary diversions. PATIENTS AND METHODS: From April 1998 through March 2003, a
      total of 49 ureters were implanted in 28 patients into various types of urinary
      diversions. Forty-six ureters were implanted transluminally (32 separately, 14
      conjointly by the double-barrelled method), 3 ureters extraluminally into
      preformed reservoirs during kidney transplantation. Forty-one ureters were
      implanted primarily, 8 ureters secondarily due to stricture of former UIA.
      RESULTS: Median observation time was 26 months. The healing was uneventful in all
      cases. Late complications were not related to the UIA. Twenty-four patients could
      be evaluated. The upper urinary tract remained stable, no reflux and no stenosis
      at the site of UIA were detected. FT anastomoses were clearly seen and easily
      accessible at endoscopy. CONCLUSION: In our hands the FT anastomosis has proved
      to be simple, safe and highly effective in terms of protecting the upper urinary
      tract against obstruction and reflux. Creation of antireflux UIA need not mean
      increased risk of obstruction in comparison with direct (reflux) ones. The FT
      technique could represent another alternative of nonrefluxing implantation of
      normal as well as dilated ureters into various types of urinary diversion.

PMID- 15474270
TI  - Ileal orthotopic bladder substitute combined with an afferent tubular segment:
      long-term upper urinary tract changes and voiding pattern.
AB  - OBJECTIVE: Assessment of the long-term morbidity of the upper urinary tract and
      of the voiding pattern in men with an ileal orthotopic bladder substitute with an
      afferent tubular segment. MATERIALS AND METHODS: Men surviving more than 5 years
      after radical cystectomy and orthotopic bladder substitution were evaluated. The
      urinary tract was regularly assessed with ultrasound and IVU while functional
      reservoir capacity and continence status were prospectively assessed by voiding
      volume diaries and a standardized questionnaire. RESULTS: After 5 years 129,
      after 10 years 45 and after 15 years 8 patients were evaluable. Median age at
      surgery was 63 years (range 36-80) and median follow-up was 73 months (range 60
      201). Of the 254 renal units assessed between April 1985 and September 1998, 199
      (78%) had some degree of dilatation in the 20-minute IVU film but rarely at 60
      minutes. In 246 (97%) the parenchyma size was normal. Ureteral obstruction
      presented in 9 (3.5%) units, 4 of which were complete (3 had obstruction
      preoperatively and 1 postoperatively). Mean creatinine levels remained unchanged
      from the preoperative values. Functional reservoir capacity averaged 462 ml after
      1 year, remained stable and then decreased slightly after 5 years. The daytime
      continence rate was 94% and 91% after 5 and 10 years, while the nighttime rate
      was 72% and 60% respectively. Patient age at the time of surgery was an important
      determinant for reservoir capacity and continence status. CONCLUSIONS: These data
      suggest that an orthotopic bladder substitution combined with an afferent tubular
      segment offers a sufficient protection of the upper tract with a low complication
      rate and has good long-term voiding and continence results. Meticulous lifelong
      follow-up is an important factor for satisfactory functional long-term outcome.

PMID- 15474271
TI  - Straightening corporoplasty for Peyronie's disease: a review of 218 patients with
      median follow-up of 89 months.
AB  - OBJECTIVE: To evaluate the outcome at long term follow-up after straightening
      corporoplasty of penile curvature due to Peyronie's disease. METHODS: Between
      1986 and 2001 a total of 279 patients with Peyronie's disease were operated on
      using the Nesbit procedure. We were able to obtain complete follow-up data in 218
      patients. The follow-up data included evaluation of complete correction of the
      curvature, penile shortening, sexual function, complications and subjective
      patient satisfaction. RESULTS: After a median follow-up of 89 months subjective
      patient determination of satisfaction indicated that 83.5% were completely
      satisfied with the results of surgery. Complete correction of the penis was
      obtained in 86.3% of the patients. One hundred and ninety patients (87.1%) had
      good erectile function (IIEF-5 >21). Shortening of the penis (from 1.5 to more
      than 3 cm) occurred in 38 patients (17.4%), but only in 5 (2.3%) was intercourse
      difficult because of excessive shortening. Major sensory changes, confined to the
      glans area, were reported by 24 patients (11%). CONCLUSION: The Nesbit operation
      is a simple and safe technique to correct the penile deformity due to Peyronie's
      disease. This technique results in the greatest amount of patient satisfaction
      about erectile function. The procedure can be used to correct all degrees of
      penile curvature successfully except for the short penis. Informed consent should
      be amply discussed before operating in regard to the risk of penile shortening
      and major sensory changes of the glans area.

PMID- 15474272
TI  - Psycho-biological correlates of rapid ejaculation in patients attending an
      andrologic unit for sexual dysfunctions.
AB  - INTRODUCTION AND OBJECTIVES: Rapid ejaculation (RE) is the most common sexual
      dysfunction in males. The aim of the present study is to determine the
      contribution of intrapsychic, organic and relational factors to the pathogenesis
      of RE and the relationship between RE and erectile dysfunction (ED) in a sample
      of patients attending for the first time to an Outpatient Clinic for sexual
      dysfunction. METHODS: We studied a consecutive series of 755 patients using
      Structured Interview on Erectile Dysfunction (SIEDY), a brief, recently
      validated, multidimensional instrument specifically designed by our group for the
      study of pathogenetic factors of ED. RE was defined as ejaculation within 1
      minute of vaginal intromission and its severity was categorized on a 4-point
      scale using a standard question. A complete physical examination and a series of
      biochemical, hormonal, psychometric, penile vascular and rigidometric evaluations
      were performed. RESULTS: Twenty-eight percent (n = 214) of patients attending to
      our sexology clinic reported RE of any degree. Patients reporting RE were younger
      (48.5 +/- 12.6 vs. 52.9 +/- 12.9 years old for RE and not RE respectively; p <
      0.0001) and showed a higher prevalence of anxiety symptoms when compared to the
      rest of the sample. Among organic factors subjects with RE showed a higher
      prevalence of hyperthyroidism and significantly lower fasting plasma glucose (94
      [87-110] and 98 [89-113] mg/dl for RE and non-RE respectively; p < 0.01). No
      difference among groups was observed for other hormones or clinical, biochemical
      and instrumental parameters. Finally RE patients showed a higher prevalence of
      partial erection sufficient for penetration when compared to the rest of the
      sample. Similar differences were observed between patients with and without RE
      when those without ED were excluded from the analysis. CONCLUSION: Our data
      suggest a minor involvement of organic factors to the pathogenesis of ED in
      patients with concomitant RE. On the other hand, in our sample, patients
      complaining about RE are younger, healthier than the rest of the sample and are
      characterized by high degree of anxiety symptoms and hyperthyroidism.

PMID- 15474273
TI  - Alpha-1-antitrypsin levels and genetic variation of the alpha-1-antitrypsin gene
      in Peyronie's disease.
AB  - OBJECTIVES: Alpha-1-antitrypsin (alpha1-antitrypsin) is a major protease
      inhibitor controlling tissue degradation. Reduced alpha1-antitrypsin levels could
      result in a change of collagen metabolism. Previous studies have described
      decreased alpha1-antitrypsin levels in patients with Peyronie's disease. However,
      only a small number of patients were analyzed, and the reason for the decreased
      alpha1-antitrypsin levels remained unclear. This study investigated prospectively
      the levels of alpha1-antitrypsin in patients with Peyronie's disease, as well as
      genetic variation in the coding region of the alpha1-antitrypsin gene. METHODS:
      Alpha1-antitrypsin levels were determined prospectively in 94 patients with
      Peyronie's disease and compared to healthy controls. Analysis of the alpha1
      antitrypsin gene (S, Z variants; single nucleotid polymorphisms [SNPs]: T-395A,
      M2, M3, G6118A) was done in 141 Peyronie's patients including 43 patients with
      investigated alpha1-antitrypsin serum levels and compared to healthy controls.
      RESULTS: In patients with Peyronie's disease, the alpha1-antitrypsin levels
      seemed to be decreased significantly compared to healthy controls. However, in
      the age matched approach no significant differences occurred. Moreover, a
      significant (p < 0.002) decrease of the alpha1-antitrypsin level with increasing
      age was observed, explaining the initial differences between the two groups. In
      confirmation with these findings, no significant association of the alpha1
      antitrypsin gene variants with Peyronie's disease was detectable. CONCLUSIONS:
      The results of this study do not indicate a significant association between
      Peyronie's disease and decreased alpha1-antitrypsin levels. Low alpha1
      antitrypsin levels in Peyronie's patients are, rather, an age-related phenomenon,
      as revealed by the comparison with aged matched healthy controls. The decrease of
      the alpha1-antitrypsin serum level with increasing age has not been described
      before.

PMID- 15474274
TI  - Pelvicol pubovaginal sling versus tension-free vaginal tape for treatment of
      urodynamic stress incontinence: a prospective randomized three-year follow-up
      study.
AB  - OBJECTIVES: The aim of this study was to compare the long-term success rates,
      complication rates and patient satisfaction rates for Pelvicol pubovaginal sling
      (Bard) versus TVT (Gynecare) in surgical treatment of urodynamic stress
      incontinence (USI) in women. DESIGN: Prospective randomized cohort trial.
      SETTING: District General Hospital, South West of England. METHODS: One hundred
      and forty-two women with urodynamic stress incontinence were randomized to either
      surgical procedure (Pelvicol = 74, TVT = 68) with median follow-up of 36 month. A
      postal questionnaire was sent to all women and the response rate was excellent at
      approximately 90% in both groups. RESULTS: Cure of incontinence, as identified by
      a quality of life improvement >90%, and/or patient-determined continent status as
      dry, were comparable in both groups. When the cure rates were adjusted assuming
      the non-respondents as failures the figures were almost identical (p > 0.05).
      Preoperative continence pad usage was similar for both groups. Overall, a
      postoperative significant decrease in pad score was noted in both groups (p =
      0.01) but there was no significant difference between the groups (p > 0.05).
      Statistical analysis failed to detect significant differences between both groups
      as regards complication rates such as frequency, nocturia, de-novo urgency or
      dyspareunia. CONCLUSION: Pelvicol sling is a safe procedure in the surgical
      management of USI with similar success rate and patient satisfaction rate to TVT
      up to three years of follow-up.

PMID- 15474275
TI  - Frequency volume charts in the assessment and evaluation of treatment: how should
      we use them?
AB  - Frequency volume charts are an essential adjunct to both the assessment of
      patients at presentation and the evaluation of new treatments for filling and
      voiding dysfunction. Since 24 hour frequency can be altered significantly by
      fluid intake and insensible fluid loss. We critically evaluated the usefulness of
      the different parameters measured on a frequency/volume chart (FVC) to determine
      which provided the most reliable information. Sixty-three patients were asked to
      complete 2 FVCs over 3 or more days with at least one week between the two
      measurements. Fifty-one patients completed the diaries and the changes in mean
      voided volume and urinary frequency were analyzed. Eight patients had significant
      differences in their mean voided volume or their 24 hour frequency, 2 patients
      had a significant difference in both mean voided volume and 24 hour frequency.
      There was an excellent correlation for both the mean voided volume (r = 0.86) and
      the 24 hour frequency (r = 0.9). The individual variation, using repeated
      measures analysis, was greater for the 24 hour frequency. There is natural
      variation of 24 hour frequency between diaries that may invalidate apparently
      successful treatment outcomes. We recommend the use of the mean voided volume as
      part of the evaluation of new treatments in chronic voiding dysfunction and
      urinary incontinence.

PMID- 15474276
TI  - The physical and antimicrobial effects of microwave heating and alcohol immersion
      on catheters that are reused for clean intermittent catheterisation.
AB  - INTRODUCTION: Due to worldwide different health insurance policies, patients are
      often forced to reuse the catheters when performing Clean Intermittent
      Catheterisation (CIC). We have compared the physical qualities and the
      antimicrobial effects of two methods of reusing catheters: microwave heating and
      storage of the catheters in a 70% alcohol solution. The studies were performed
      during different lengths of time. MATERIALS AND METHODS: Three types of catheters
      (a standard polyvinylchloride catheter, a special polyvinylchloride catheter with
      flexible Ergothan tip and a prelubrified catheter), normally intended for single
      use, were submitted to the effect of a microwave oven (Multitech 215 High Grade
      and Whirlpool M220 750 W and 1000 W with rotating plate) or preservation in a 70%
      alcohol solution. To study the effects of microwave heating, a recipient of water
      was placed in the oven to spread the microwaves and to absorb the heat. The
      catheters were placed in a resealable plastic bag (Ziploc. To study the effects
      of preservation in a 70% alcohol solution, the catheters were immerged in the
      solution for different lengths of time. Thereafter were the physical qualities of
      the catheters evaluated by using the technique of Differential Scanning
      Calorimetry (DSC). The antimicrobial effect of the method was evaluated after
      grafting the catheters with pathogenic E. coli, P. aeruginosa or S. aureus
      strains. RESULTS: Microwave heating up to 12 minutes at 750 W caused only minimal
      changes in the physical qualities of all the catheters. However, there was only
      an antimicrobial effect of the microwave heating on E. coli and not on P.
      aeruginosa or S. aureus. If the catheter remained longer than 45 minutes in a 70%
      alcohol solution, the physical qualities of the catheter changed either minimal
      in the special polyvinylchloride catheter with flexible Ergothan top but changed
      significantly in the prelubrified catheter). However, already after 5 minutes of
      immersion in the 70% alcohol solution there was a complete antimicrobial effect
      on E. coli, P. aeruginosa and S. aureus in all catheters. CONCLUSIONS: It should
      be recommended to patients on CIC to use a sterile packed and not previously used
      catheter. In this study we have shown that immersing the catheters in a 70%
      alcohol solution during 5 minutes can effectively disinfect the catheter without
      jeopardising the physical qualities. Thereafter, the catheters could be placed in
      a resealable (e.g. Ziploc bag without being rinsed under water, in order that the
      few drops of alcohol cause alcohol vapours within the closed plastic bag and
      maintain the antimicrobial effect.

PMID- 15474277
TI  - In vitro activity of fluoroquinolones, azithromycin and doxycycline against
      chlamydia trachomatis cultured from men with chronic lower urinary tract
      symptoms.
AB  - INTRODUCTION: Little is known about chlamydia survival in the presence of
      fluoroquinolones in patients with chronic prostatitis syndrome (CPS). In vitro
      activities of four fluoroquinolones, azithromycin and doxycycline against C.
      trachomatis in patients with CPS being not treated with antibiotics earlier were
      investigated and compared. MATERIAL AND METHODS: Chlamydia survival in 304
      patients with CPS being not treated with antibiotics earlier was analysed and
      compared. Infection by C. trachomatis was determined in the urethra and expressed
      prostatic secretion by cell culture test. RESULTS: Azithromycin and ofloxacin
      were found to be the most active antichlamydial agent with ciprofloxacin and
      doxycycline being least active. CONCLUSION: Ofloxacin can be recommended as the
      primary drug in the treatment of chlamydia-infected patients with CPS. The
      decision on the prescription of other fluoroquinolones should be made
      individually. The investigation of chlamydia survival in the presence of
      antibiotics in patients with CPS and C. trachomatis prior to treatment is
      recommended.

PMID- 15474278
TI  - Pelvic floor spasms in children: an unknown condition responding well to pelvic
      floor therapy.
AB  - OBJECTIVE: During a study period of 4 years, 21 children are seen for night time
      pelvic pain. These children typical wake up in the middle of the night with
      severe lower abdominal or perineal pain. During day some of them suffer urge
      syndrome. During urodynamic investigation extremely high pelvic floor activity as
      recorded by high urethral pressure was observed in these children. We therefore
      started pelvic floor relaxation biofeedback in these children. METHODS: All
      children diagnosed with pelvic floor spasms underwent biofeedback pelvic floor
      relaxation therapy in order to learn them to counteract pelvic pain due to these
      spasms. In those girls in whom detrusor hyperactivity was seen on urodynamics
      concomitant anticholinergic treatment was given (oxybutynin). RESULTS: Between
      January 1998 and January 2002 symptomatic pelvic floor spasms were diagnosed in
      21 children (19 girls/2 boys). Pelvic floor relaxation biofeedback was successful
      for treatment of this condition in 17 of 21 children. Mean duration of therapy
      was 3 months (12 weekly sessions) and on long term follow-up relapse was seen in
      3 of 17 successfully treated children. 10 of 17 successfully treated children
      received anticholinergics. CONCLUSION: Pelvic floor spasms in children (which can
      be secondary to detrusor overactivity) respond well to pelvic floor relaxation
      therapy.

PMID- 15474279
TI  - Tubularized incised plate urethroplasty: 5 years' experience.
AB  - OBJECTIVE: To evaluate the results of tubularized incised plate (TIP)
      urethroplasty in a series of primary hypospadias repairs. PATIENTS AND METHOD:
      The medical records of 360 children (Mean age: 4.3 years, range: 2-14 years) with
      primary hypospadias undergoing TIP urethroplasty repair and treatment of
      complications were reviewed. A good result is a direct urinary steam through a
      slit and vertically oriented meatus and mild angled urinary stream through a
      slightly regressed meatus is a satisfactory result. RESULTS: The sum of good
      (74%) and satisfactory results (3%) was the overall success rate (77%) which was
      increased to 95% after a second surgical procedure for the treatment of
      complications. In 30 patients with single fistula (8%), fistula healed
      spontaneously in 2 patients and 20 patients had successful fistula closure. Redo
      TIP urethroplasty (n = 30) was performed for dehiscence (n = 15, 3%), neourethral
      stricture (n = 3, 1%) and multiple fistula with meatal stenosis (n = 12, 3%). The
      complication rate after redo TIP urethroplasty is 30%. Twenty-four (7%) patients
      underwent meatoplasty for meatal stenosis. CONCLUSION: TIP urethroplasty can be
      used to repair primary hypospadias. After a learning curve and attention to
      surgical details, cosmetic and functional outcome become excellent. Redo TIP
      urethroplasty can be performed in the treatment of complications.

PMID- 15474280
TI  - Molecular detection of prostate cancer: a role for GSTP1 hypermethylation.
AB  - OBJECTIVE: Prostate cancer is a leading cause of cancer-related mortality and
      morbidity in Western world. Curative treatment is feasible provided the disease
      is diagnosed in its earliest stages, but current screening methodologies are
      characterized by low specificity. DNA-based markers are a class of new and
      promising tools for cancer detection. Promoter hypermethylation is a common
      epigenetic alteration affecting cancer-related genes. METHODS: We critically
      reviewed the most relevant reports on prostate cancer detection using DNA
      methylation analysis in prostate tissue and body fluids. RESULTS: The epigenetic
      silencing of the glutathione-S-transferase P1 (GSTP1) gene is the most common
      (>90%) genetic alteration so far reported in prostate cancer. Methylation
      specific PCR (MSP) methods allowed for the successful detection of GSTP1
      methylation in body fluids (serum, plasma, urine, and ejaculates) from prostate
      cancer patients. In addition, the development of highly specific quantitative MSP
      assays augmented standard histopathology for the diagnosis of prostate cancer in
      tissue biopsies, accurately distinguishing benign from malignant prostate
      lesions. CONCLUSIONS: Further advances in the epigenetic characterization of
      prostate cancer are likely to yield powerful tools for patient diagnosis and
      management.

PMID- 15474281
TI  - The effect of hyperthermia on mitomycin-C induced cytotoxicity in four human
      bladder cancer cell lines.
AB  - INTRODUCTION: Hyperthermia and mitomycin-C (MMC) have given very encouraging
      results in several clinical studies for the treatment of superficial transitional
      cell carcinoma of the bladder. However, a synergistic effect of hyperthermia and
      MMC on the decrease of cell proliferation has never been demonstrated accurately
      in vitro. We investigated the effect of MMC versus MMC combined with hyperthermia
      on the cytotoxicity in four human bladder cancer cell lines. MATERIAL AND
      METHODS: The RT112, RT4, 253J and T24 human bladder cancer cell lines were seeded
      in 96-well microtiter plates at 2.0 x 10(4) cells per well and were left to
      attach for 24 hours. The cells were then treated for 60 minutes with MMC
      concentrations ranging from 0 to 400 microg/ml at a temperature of 37 degrees C
      or 43 degrees C. After treatment cells were rinsed three times with culture
      medium and left for 24 hours in the incubator. Dimethyl thiazolyl tetrazolium
      (MTT) solution was added and after 4 hours of incubation the MTT containing media
      was aspired from all wells and 100 microl of dimethyl sulfoxide was added to each
      well. A spectrum analyses was performed at 595 nm light wavelength. RESULTS: A
      decrease of cell proliferation after treatment with increasing concentrations MMC
      was demonstrated. Hyperthermia has a synergistic effect on the decrease of cell
      proliferation by different concentrations MMC. In the cells treated without MMC
      no significant difference in the extent of cell killing at 37 degrees C and 43
      degrees C was observed. Furthermore, no difference was observed between cells
      with a p53 protein mutation (RT112 and T24) or without a p53 protein mutation
      (253J and RT4). CONCLUSION: A clear synergistic effect of MMC and hyperthermia
      has been demonstrated in four human bladder cancer cell lines.

PMID- 15474283
TI  - Routine cystoscopy is not needed in TOT outside-in.

PMID- 15474284
TI  - Molecular biology of gastric cancer: Helicobacter infection and gastric
      adenocarcinoma: bacterial and host factors responsible for altered growth
      signaling.
AB  - Gastric cancer remains the second most common cause of cancer-related mortality
      worldwide. The single most common cause of gastric cancer is chronic infection
      with the gram-negative microaerophilic spiral bacterium: Helicobacter pylori.
      Recent advances in this field have identified host factors which predispose to
      gastric cancer formation via modulation of the host immune response. In addition,
      recent work has explored bacterial virulence factors which may directly cause
      tissue damage, and lead to gastric carcinogenesis, as well as factors responsible
      for enhanced immune response. Environmental factors, long associated with a
      predilection for gastric cancer, are recognized as modifiers of key growth
      signalling pathways within the gastric mucosa and as such lead to growth
      alterations. This review focuses on exploring new advances in our understanding
      of bacterial factors, host genetic polymorphisms and the interaction between the
      bacterium and host at the level of the immune response and the regulation of
      proliferative and apoptotic signal transduction cascades. Modulation of the
      pivotal balance between cell growth and cell death leads to the formation of
      gastric adenocarcinoma.

PMID- 15474285
TI  - Wnt signaling in osteoblasts and bone diseases.
AB  - Recent revelations that the canonical Wnt signaling pathway promotes postnatal
      bone accrual are major advances in our understanding of skeletal biology and
      bring tremendous promise for new therapeutic treatments for osteoporosis and
      other diseases of altered bone mass. Wnts are soluble glycoproteins that engage
      receptor complexes composed of Lrp5/6 and Frizzled proteins. A subgroup of Wnts
      induces a cascade of intracellular events that stabilize beta-catenin,
      facilitating its transport to nuclei where it binds Lef1/Tcf transcription
      factors and alters gene expression to promote osteoblast expansion and function.
      Natural extracellular Wnt antagonists, Dickkopfs and secreted frizzled-related
      proteins, impair osteoblast function and block bone formation. In several genetic
      disorders of altered skeletal mass, mutations in LRP5 create gain-of-function or
      loss-of-function receptors that are resistant to normal regulatory mechanisms and
      cause higher or lower bone density, respectively. In this review, we summarize
      the available molecular, cellular, and genetic data that demonstrate how Lrp5 and
      other components of the Wnt signaling pathway influence osteoblast proliferation,
      function, and survival. We also discuss regulatory mechanisms discovered in
      developmental and tumor models that may provide insights into novel therapies for
      bone diseases.

PMID- 15474286
TI  - Serine-arginine-rich nuclear protein Luc7l regulates myogenesis in mice.
AB  - Using a gene trap technique, we identified a murine homologue of the yeast LUC7
      like gene (Luc7l), which is a serine-arginine-rich protein (SR protein) that
      localizes in the nucleus through its arginine-serine-rich domain (RS domain) at
      the C-terminus and shows a speckled distribution pattern. Although its
      transcripts are widely expressed in embryos and adults, they are rarely detected
      in adult skeletal muscle, and Luc7l expression was found to be negatively
      regulated during the course of development of limb skeletal muscle, as well as
      during in vitro differentiation of the myoblast cell lines Sol8 and C2C12. We
      also demonstrated that forced expression of Luc7l protein inhibited myogenesis in
      vitro. Based on our results, Luc7l is thought to play an important role in the
      regulation of muscle differentiation.

PMID- 15474287
TI  - Identification of a 49-bp fragment of the HvLTP2 promoter directing aleurone cell
      specific expression.
AB  - Identification of regulatory elements directing definite and specific
      spatiotemporal expression patterns is a prerequisite to the next generation of
      transgenic plants with commercial and ethical feasibility for producing
      plantibodies or other pharmaceutically important compounds. Here we describe the
      functional dissection of the barley nonspecific lipid transfer protein gene
      promoter, HvLTP2. The gene is specifically expressed in aleurone cells of cereals
      and used as an aleurone marker in maize and rice. The transcript is uniformly
      localised in the barley aleurone cells from around 10 DAP. Patchy expression in
      aleurone cells of transgenic rice has been reported and explained by silencing of
      transgenes. We have performed deletion analyses of the 801-bp HvLTP2 promoter to
      gain insight into the molecular basis of its regulation and the presence of
      putative regulatory elements. From the deletion studies, a 49-bp promoter region
      directing aleurone-specific expression was identified. Simultaneously, in vivo
      footprinting was carried out to identify promoter elements bound by putative
      regulatory proteins. Within the 49-bp fragment, the most promising candidate for
      a minimal cis-acting regulatory region directing aleurone specificity is the ds
      sequence. Based on our results, we hypothesise that the ds-sequence directs
      aleurone specificity, possibly through a concerted action with elements directing
      general expression in the seed. Moreover, we present an overview of LTP2 elements
      putatively involved in directing seed, endosperm, and aleurone expression.
      Additionally, we report HvLTP2 expression in the embryo, not previously detected.
      The regulatory element(s) directing expression in embryo is located downstream of
      the 49-bp fragment directing aleurone specificity, thus demonstrating independent
      control of aleurone and embryo-localised expression. Finally, we discuss the
      existence of several endosperm-specific boxes and whether alternative promoter
      elements and combinations of them may direct aleurone expression, explaining why
      comparing different genes expressed in aleurone fail to identify only one
      required, common promoter element.

PMID- 15474288
TI  - Cell targeted phagemid rescued by preselected landscape phage.
AB  - We have developed a gene delivery system that utilizes a cell-binding helper
      phage preselected from a landscape phage display library, and a phagemid
      harboring a marker gene and all regulatory elements (origins of replication and
      promoter-enhancer cassettes) necessary for replication of the phagemid and
      expression of the marker gene in the targeted cell. All the proteins required for
      encapsulation of the phagemid DNA and cell targeting are provided by the phage
      helper and are separate from the phagemid. Therefore, the resultant Phagemid
      Infective Particles (PIPs) are able to bind and infect target cells and express
      the marker gene from within the cell. Our approach, shown here for glioma cells,
      differs from others in that a phagemid expressing a model marker or particular
      therapeutic gene can be easily exchanged for a phagemid expressing a different
      therapeutic gene. Also, a different helper phage, selected from a phage display
      library, such as the f8-8-mer landscape library used here, can target any cell
      type and direct the encapsulation of any therapeutic gene encoding phagemid.
      Because of its versatility, the PIPs system may be readily used for optimization
      of the gene-delivery strategies applied to specific cell and tissue targets.

PMID- 15474289
TI  - Identification of a novel aminergic-like G protein-coupled receptor in the
      cnidarian Renilla koellikeri.
AB  - Biogenic amines exert various physiological effects in cnidarians, but the
      receptors involved in these responses are not known. We have cloned a novel G
      protein-coupled receptor cDNA from an anthozoan, the sea pansy Renilla
      koellikeri, that shows homology to mammalian catecholamine receptors and, to a
      lesser extent, to peptidergic receptors. This putative receptor, named Ren2, has
      a DRC pattern that replaces the well-conserved DRY motif on the cytoplasmic side
      of the transmembrane III and lacks the cysteine residues usually found in the
      second extracellular loop and C-terminus tail. Both the second extracellular loop
      and the N-terminal tail were seen to be short (six and three amino acids,
      respectively). Northern blot analysis suggests that the receptor gene codes for
      two transcripts. Localization of these transcripts by in situ hybridization
      demonstrated abundant expression in the epithelium of the pharyngeal wall, the
      oral disk and tentacles as well as in the endodermal epithelium lining the
      gastrovascular cavities.

PMID- 15474290
TI  - High-efficiency gene delivery for expression in mammalian cells by
      nanoprecipitates of Ca-Mg phosphate.
AB  - Transfer of desirable genetic sequences into mammalian cells is an essential tool
      for analysis of gene structure, functions and regulation and industry-based
      production of therapeutically important proteins and pivotal for gene therapy and
      DNA vaccination strategies. Considering some severe limitations of viral systems
      including immunogenicity, carcinogenicity and so on, synthetic nonviral systems
      are highly desirable in the above applications. However, existing nonviral
      techniques are extremely inefficient compared to the viral ones. Therefore, we
      report here on the development of a highly efficient synthetic device for gene
      delivery and expression into mammalian cells, based on controllable growth of
      nanoapatite particles. Mg2+ incorporation into the apatite particles caused
      significant inhibition of particle growth, resulting in retention of nanosized
      particles which contributed remarkably to the cellular uptake of DNA and its
      subsequent expression (>10-fold) compared with classical calcium phosphate
      coprecipitation, one of the most widely used transfection methods.

PMID- 15474291
TI  - Transcript profiling of salinity stress responses by large-scale expressed
      sequence tag analysis in Mesembryanthemum crystallinum.
AB  - The common ice plant, Mesembryanthemum crystallinum, is a halophytic (salt
      loving) member of the Aizoaceae, which switches from C3 photosynthesis to
      Crassulacean acid metabolism (CAM) when exposed to salinity or water-deficit
      stress. CAM is a metabolic adaptation of photosynthetic carbon fixation that
      improves water use efficiency by shifting net CO2 uptake to the night, thereby
      reducing transpirational water loss. To improve our understanding of the
      molecular genetic underpinnings and control mechanisms for Crassulacean acid
      metabolism (CAM) and other salinity stress response adaptations, a total of 9733
      expressed sequence tags (ESTs) from cDNAs derived from leaf tissues of well
      watered and salinity-stressed (0.5 M NaCl for 30 and 48 h) were characterized.
      Clustering and assembly of these ESTs resulted in the identification of a total
      of 3676 tentative unique gene sequences (1249 tentative consensus sequences and
      2427 singleton ESTs) expressed in leaves of ice plant under unstressed and
      salinity stressed conditions. The same number (2782) of ESTs from each library
      (total=8346 ESTs) were randomly selected and analyzed to compare expression
      profiles among the control and salt stressed leaf tissues. EST frequencies for
      transcripts encoding CAM-related enzymes, pathogenesis-related, senescence
      associated, cell death-related, and stress-related proteins such as heat shock
      proteins (HSPs), chaperones, early light-inducible proteins, ion homeostasis,
      antioxidative stress, detoxification, and biosynthetic enzymes for
      osmoprotectants increased 2-12-fold in cDNA libraries constructed from salt
      stressed plants. In contrast, the frequency of ESTs encoding light-harvesting and
      photosystem complexes and C3 photosynthetic enzymes decreased 4-fold overall
      following salinity stress with transcripts for ribulose bisphosphate
      carboxylase/oxygenase (RuBisCO) subunits decreasing 7-fold. Moreover, stressed
      plants contained a higher percentage of ESTs encoding novel and/or functionally
      unknown proteins. The rapid discovery of both known and unknown genes related to
      stress responses in M. crystallinum demonstrates the great utility of EST
      analysis in unraveling the complex set of adaptive mechanisms contributing to
      water use efficiency (CAM) and salinity tolerance.

PMID- 15474292
TI  - Translational control of the rat angiotensin type 1a receptor by alternative
      splicing.
AB  - The rat angiotensin type 1a receptor (AT1aR) is comprised of three exons. Two
      transcripts are possible due to alternative splicing of exon 2 (E1,3 and E1,2,3).
      Both transcripts code for identical AT1aR proteins since they differ only in the
      length of their 5' leader sequence (5'LS). We investigated the functional
      differences of these two transcripts in stably transfected Chinese hamster ovary
      (CHO) cells and also determined the splice variant composition in rat tissues.
      E1,3 expressing cells exhibited 1.8-fold higher AT1R densities and five-fold
      higher levels of Ang II-stimulated inositol phosphate production compared to
      E1,2,3 expressing cells. No differences in E1,3 and E1,2,3 mRNA levels or mRNA
      stability were seen. In vitro translation assays revealed 1.8-fold higher AT1aR
      protein levels from E1,3 compared to E1,2,3 transcripts, suggesting exon 2
      reduces functional AT1R expression by inhibiting translation. Deletion of 10
      nucleotides in exon 2 increased translation of the mutated E1,2,3 transcript to
      levels which were indistinguishable from E1,3, suggesting that this loop region
      of a predicted hairpin contributes to the inhibitory RNA cis element within exon
      2. Comparison of AT1aR exonic composition and AT1R densities in rat tissues
      suggests alternative splicing is regulated in a tissue-specific manner and
      contributes to tissue-specific differences in AT1R density.

PMID- 15474293
TI  - Molecular cloning, structure, expression, and chromosomal localization of the
      human Osterix (SP7) gene.
AB  - We report the isolation of the human orthologue of the mouse Osterix (Osx/Sp7)
      gene, a C2H2 zinc finger transcription factor of the SP gene family and putative
      "master" regulator of bone cell differentiation. The human SP7 cDNA encodes a
      putative 431 amino acid protein that contains three consecutive C2H2 zinc finger
      repeats. The SP7 protein is highly conserved between mice and humans with an
      overall sequence identity of 95%. The expression of a SP7 mRNA transcript of
      approximately 3.2 kb is restricted to bone-derived cell lines in vitro but
      undetectable in any adult tissues including mandibular bone by Northern blot
      hybridization. The specific expression of SP7 mRNA in osteoblasts in vivo was
      further confirmed by in situ hybridization on human embryonic tissues. The highly
      restricted expression pattern and the divergence of the sequence outside of the
      zinc finger region distinguish SP7 as a unique member of the SP family. The SP7
      gene consists of two exons, with exon 2 containing most of the protein coding
      sequence. The gene locus was mapped to chromosome 12q13.13 by fluorescent in situ
      hybridization (FISH). The identification and initial characterization of the SP7
      gene will facilitate the study of the molecular regulation of osteoblast
      differentiation in humans.

PMID- 15474294
TI  - Rearing density influences the expression of stress-related genes in sea bass
      (Dicentrarchus labrax, L.).
AB  - The worldwide decline of ocean fisheries stocks has provided a rapid growth in
      fish farming and the problems connected to animal welfare in aquaculture gained
      importance. In this context, we have looked for molecular markers among those
      genes whose expression could reasonably result modified by the different farming
      conditions. With this purpose, we have evaluated, in liver and brain of sea
      basses, grown for 3 months at different biomass density (<10, 80 and 100 kg/m3),
      the expression of those genes coding for proteins related to stress such as Heat
      Shock Proteins (HSPs), Metallothioneins (MTs) and Cytochrome P4501A (CYP4501A).
      In liver, the expression of MT and CYP4501A mRNA resulted induced in animals
      reared at 80 and 100 kg/m3. Inducible HSP70 appeared significantly over expressed
      only at the biomass of 100 kg/m3, while apparently, no induction was detectable
      for HSP90. In brain tissue instead, MT and HSP90 were induced already at 80
      kg/m3; CYP4501A and HSP70 were influenced only at the higher population density
      of 100 kg/m3. In the last three decades, there has been an exponential increase
      in the interest concerning the description, classification and functional
      significance of stress-related proteins, in particular HSPs. These proteins
      represent precious biomarkers to evaluate the welfare conditions when they are
      still recoverable; detecting their mRNA by PCR is fast, easy and relatively
      inexpensive. Therefore, we propose this method as a good alternative to monitor
      fish welfare.

PMID- 15474295
TI  - The SAT1 flipper, an optimized tool for gene disruption in Candida albicans.
AB  - The construction of Candida albicans mutants by targeted gene disruption usually
      depends on the use of nutritional markers for the selection of prototrophic
      transformants from auxotrophic host strains, but it is becoming increasingly
      evident that this strategy may cause difficulties in the interpretation of mutant
      phenotypes. Here, we describe a new method for inactivating both alleles of a
      target gene in C. albicans wild-type strains to obtain homozygous null mutants.
      The SAT1 flipping method relies on the use of a cassette that contains a dominant
      nourseothricin resistance marker (caSAT1) for the selection of integrative
      transformants and a C. albicans-adapted FLP gene that allows the subsequent
      excision of the cassette, which is flanked by FLP target sequences, from the
      genome. Two rounds of integration/excision generate homozygous mutants that
      differ from the wild-type parent strain only by the absence of the target gene,
      and reintegration of an intact gene copy for complementation of mutant phenotypes
      is performed in the same way. Transformants are obtained after only 1 day of
      growth on a selective medium, and integration into the target locus occurs with
      high specificity after adding homologous flanking sequences on both sides of the
      cassette. FLP-mediated excision of the SAT1 flipper cassette is achieved by
      simply growing the transformants for a few hours in medium without selective
      pressure, and nourseothricin-sensitive (NouS) derivatives can easily be
      identified by their slower growth on indicator plates containing a low
      concentration of nourseothricin. We demonstrate the use of the system by deleting
      the OPT1 gene, which encodes an oligopeptide transporter, in the C. albicans
      model strain SC5314. The null mutants became resistant to the toxic peptide
      KLLEth, and reintroduction of an intact OPT1 copy restored susceptibility. The
      SAT1 flipping method provides a highly efficient method for gene disruption in C.
      albicans wild-type strains, which eliminates currently encountered problems in
      the genetic analysis of this important human fungal pathogen.

PMID- 15474296
TI  - Regulation of transcription of the human MRP7 gene. Characteristics of the basal
      promoter and identification of tumor-derived transcripts encoding additional 5'
      end heterogeneity.
AB  - Studies focusing on the transcriptional regulation of MRP7 (multidrug resistance
      associated protein 7) gene expression in human tumor cells are described. As
      shown by real-time RT-PCR, expression of the MRP7 gene compared to the expression
      of the MRP1, 2 and 3 genes was less variable among the different cell types.
      MRP1, 2, 3 and 7 gene expression was highest in HepG2 cells compared to
      expression in CWR22Rv1 and TSU-PR1 cells. MRP7 gene expression was less than
      expression of the MRP1 and 2 genes in HepG2 cells but similar to MRP3 gene
      expression in this cell type and similar to or greater than expression of the
      MRP1, 2 and 3 genes in CWR22Rv1 and TSU-PR1 cells. Functional deletion analysis,
      in situ mutagenesis and electromobility shift assays (EMSA) showed that basal
      MRP7 promoter activity relied upon a proximal segment of the 5' flanking region
      169 to 257 nt in length bearing an E2F site acting cooperatively with two closely
      positioned Sp1 sites. Two additional Sp1 sites further downstream were of
      secondary importance. The sequence of the E2F site was noncanonical and its
      interaction with E2F protein was confirmed by a competitive EMSA using a
      consensus E2F oligonucleotide probe and by demonstrating a supershift with the
      antibody against the E2F4 and E2F5 pocket protein, p107. 5' RACE carried out with
      CWR22Rv1 and HepG2 cells detected a single transcription start site (tsp) distal
      to the basal promoter and identified two new MRP7 transcripts with very short 5'
      UTR sequences compared to transcripts found by others in nontumorous human
      tissue. This 5' end heterogeneity infers a more complex intron-exon composition
      than hitherto shown.

PMID- 15474297
TI  - The antiapoptotic gene Ian4l1 in the rat: genomic organization and promoter
      characterization.
AB  - Rat immune-associated nucleotide 4-like 1 (Ian4l1) encodes an antiapoptotic
      protein, which is essential for T-cell survival. A frameshift mutation at codon
      85 in the biobreeding diabetes-prone (BBDP) rat is the cause of their life-long T
      cell lymphopenia, which includes lack of regulatory T-cells--a prerequisite for
      spontaneous autoimmune destruction of their beta-cells. This study reports the
      identification of seven Ian4l1 mRNA variants. The genomic organization of the
      exons indicates three promoter regions. The promoter of two of the mRNAs was
      characterized. Rapid amplification of cDNA ends (RACE) and ribonuclease
      protection assay (RPA) demonstrated multiple transcription start sites (TSS) with
      two major sites. The localization of the core promoter and regulatory regions was
      identified by a luciferase assay of the 2.7-kb upstream of the TSS. The
      regulatory regions functioned similarly in two cell lines--one expressing Ian4l1
      and one not expressing it. This indicates that the cell-specific expression is
      controlled by regions outside the 2.7-kb region, or by the chromatin structure or
      chromatin methylation level. The core promoter is TATA-less and initiator element
      less, and contains putative binding sites for YY1, Sp1, and MED-1, the latter
      being an element believed to be important for transcription from TATA-less
      promoters.

PMID- 15474298
TI  - Some microsatellites may act as novel polymorphic cis-regulatory elements through
      transcription factor binding.
AB  - Although microsatellites with functional effects have been described, generally,
      these repeats are considered as "junk" DNA in the same way as other repetitive
      sequences. Our aim was to investigate if certain microsatellites can have a
      functional role as cis-regulatory elements. A database was created of all short
      tandem repeats, from 2 to 10 bases, located in the first 10-kb 5' of the
      transcription start sites of all annotated genes of the human genome. Of 114
      microsatellites selected based on their size and location in the promoter, 51
      were found to be polymorphic. Using electrophoretic mobility shift assay (EMSA),
      we studied five repetitive motifs and three displayed specific protein binding
      which were found in 12 of the polymorphic microsatellites. An interesting
      microsatellite is the CTC/GAG repeat which, as double-stranded (DS) DNA, bound
      specificity protein 1 (SP1) with high affinity, formed triplexes in vitro and
      displayed differences in SP1 binding and triplex formation capacity for repeats
      with distinct numbers of repeat units. Interestingly, the polypyrimidine strand
      of the repeat (CTC) bound other proteins such as polypyrimidine tract-binding
      protein 1 (PTBP1) as single-stranded (SS) DNA, and a model with two alternative
      DNA conformations is proposed for these repeats. Distinct protein binding to DS
      DNA was also observed for different numbers of AAACA and AAAAT repeats. Our
      results suggest that certain microsatellites may act as cis-regulatory elements,
      controlling gene expression through transcription factor binding and/or secondary
      DNA structure formation. Due to their high polymorphism and abundance, they might
      represent an important source of quantitative genetic variation.

PMID- 15474299
TI  - Characterization of a second functional gene cluster for the catabolism of
      phenylacetic acid in Pseudomonas sp. strain Y2.
AB  - Pseudomonas sp. strain Y2 is a styrene degrading bacterium that mineralises this
      compound through its oxidation to phenylacetic acid (PAA). We previously
      identified a complete gene cluster (paa1 cluster) for the degradation of
      phenylacetate, but, surprisingly, some paa1 deletion mutants were still able to
      catabolize styrene (STY) suggesting that this strain contained a second catabolic
      pathway. We report here the characterization of a second and novel paa2 gene
      cluster comprising 17 genes related to the catabolism of phenylacetate. We have
      identified a new gene (paaP) that is most likely involved in a transport process.
      Remarkably, the organization of the paa2 gene cluster is more similar to that of
      Pseudomonas putida KT2440 than to the paa1 gene cluster. Two new genes of
      undefined function were located inside the paa2 cluster. Sequence comparison
      between the paa2 genes and the paa1 and paa clusters of Pseudomonas sp. strain Y2
      and P. putida KT2440, respectively, revealed a similar degree of divergence among
      the three sets of genes. Differences in the gene organization between paa1 and
      paa2 clusters of Pseudomonas sp. strain Y2 can be explained by an independent
      evolutionary history, probably associated with the adjacent sty genes. Deletion
      of either the first (paa1) or the second (paa2) gene cluster did not affect the
      ability of strain Y2 to grow in phenylacetate, whereas the deletion of both
      clusters led to the loss of this ability. The co-existence of two functional gene
      clusters for the degradation of phenylacetic acid in a bacterium has not been
      reported so far.

PMID- 15474300
TI  - Cloning, gene organization and identification of an alternative splicing process
      in lecithin:retinol acyltransferase cDNA from human liver.
AB  - Lecithin:retinol acyltransferase (LRAT) catalyzes the synthesis of retinyl esters
      in many tissues and is crucial for the transport and intracellular storage of
      vitamin A. LRAT expression is highly regulated in the liver. In this study, we
      have cloned and sequenced the full-length LRAT mRNA from human liver and
      identified its 5'- and 3'-ends. Full-length LRAT mRNA comprises 5023 nt with a
      predicted ORF of 230 amino acids, a short 5'UTR, and a relatively long 3'UTR of 4
      kb containing several polyadenylation signals and AU-rich regions. Based on
      alignment of this mRNA with human genomic DNA in the GenBank database, the human
      LRAT gene spans about 9.1 kbp and consists of two exons and a relatively long 4
      kbp intron. Further analysis of normal liver revealed a minor alternative
      splicing variant which lacks a 103 nt polynucleotide contained in the 5'UTR of
      the full-length LRAT transcript. This variant predicts that the LRAT gene is
      organized into three exons and two introns, as reported for LRAT cloned from
      retinal pigment epithelium (RPE) cells. These two LRAT mRNA variants are also
      present in testis, which is known to express LRAT and contain retinyl esters.
      Major and minor transcription start sites for human liver LRAT mRNA were
      identified and the sequence of the upstream proximal promoter region was
      retrieved from the GenBank database and physically analyzed for the presence of
      putative cis-acting elements essential for basal transcription. This region
      contains a TATA box, CCAAT box and Sp1 site, which are apparently conserved in
      mouse and rat LRAT genes. Our results provide evidence that multiple LRAT mRNA
      transcripts, which are expressed in a tissue-specific manner, may result from
      several mechanisms including differential splicing of the 5'UTR region and the
      use of multiple polyadenylation signals in the 3'UTR.

PMID- 15474301
TI  - Isolation and characterization of Rac1 pseudogenes (psi1Rac1-psi4Rac1) in the
      human genome.
AB  - Ras-related C3 toxin substrate 1 (Rac1) is a small Rho-GTPase with important
      functions in fundamental cellular processes such as cytoskeleton rearrangements,
      signal transduction, cell cycle progression and malignant transformation. Using
      Rac1 primer, we identified a 5.5-kb DNA sequence on chromosome 4 (Chr. 4) in the
      human genome, containing the intronless protein coding sequence of Rac1. Sequence
      analysis revealed features of a processed pseudogene, which we named psi1Rac1,
      that could be detected by Southern blot and polymerase chain reaction (PCR) on
      genomic DNA. A psi1Rac1 pseudogene transcript was not detected by reverse
      transcription-polymerase chain reaction (RT-PCR), nor had the psi1Rac1 promoter
      any transcriptional activity. In addition, three other intronless pseudogenes of
      Rac1 on chromosomes 4, 13 and X were identified (psi1Rac1-psi4Rac1) sharing an 86
      96% sequence similarity with Rac1. Neither RT-PCR with pseudogene specific
      restriction enzymes, nor the sequencing of 130 cDNA clones from benign and
      malignant breast tissue and cell lines, detected the transcription of any of the
      Rac1 pseudogenes (psi2Rac1-psi4Rac1). Existence of Rac1 pseudogenes should be
      taken into consideration when analyzing genomic alterations of the human Rac1
      gene.

PMID- 15474302
TI  - A novel microarray to evaluate stress-related genes in skin: effect of
      ultraviolet light radiation.
AB  - We tested transcriptional responses to ultraviolet radiation in epidermal
      keratinocytes using microarray chips containing more than 700 neuroendocrine
      immune-related genes. The gene expression pattern was nonrandom and time
      dependent; it included increased expression of genes involved in water and salt
      balance, prostaglandin synthesis, keratinocyte differentiation as well as genes
      coding for stress effectors, cytokines and metalloproteinases (MMPs). In
      contrast, expression was decreased for genes coding for growth factors and their
      receptors and for elements of extracellular matrix. This pattern suggests that
      transcriptional responses are coordinated and aimed at the preservation of
      epidermal barrier function, prevention of early carcinogenic events and
      remodeling of extracellular matrix. In summary, we have developed a microarray
      chip that can be used for simultaneous testing of transcriptional responses to
      cutaneous stressors in the context of neuroendocrine-immune functions of the
      skin.

PMID- 15474303
TI  - E2F sites in the Op18 promoter are required for high level of expression in the
      human prostate carcinoma cell line PC-3-M.
AB  - Op18 (Oncoprotein 18, Stathmin) is an important mitotic regulator that is highly
      expressed in many cancers including the metastatic prostate carcinoma cell line
      PC-3-M. Recent studies indicate that antisense-mediated down-regulation of Op18
      can inhibit cellular proliferation. However, the transcriptional mechanisms
      responsible for its normal regulation and for its high level of expression in
      proliferating cells remain poorly understood. In the study presented here, we
      have characterized transcription factor binding sites that together account for
      nearly 80% of the Op18 expression in PC-3-M cells. The 5' flanking region of the
      Op18 gene contains four putative E2F sites located at -700 (site 1), -28 (site
      2), -19 (site 3), and +720 (site 4) relative to the transcriptional start site.
      E2F has been implicated in both the c-Jun-mediated up-regulation and the
      doxorubicin-induced repression of Op18 expression. We have used promoter-reporter
      assays and mobility shift assays to functionally examine each of these E2F sites.
      Mutagenesis studies indicate that all sites contribute to the basal expression of
      Op18. Mutagenesis of either site 1 or 4 reduced the reporter activity by 40%,
      mutagenesis of site 2 reduced reporter activity by 20%, and mutations in site 3
      had no effect on reporter activity. Combinatorial mutagenesis indicates that site
      1 and 4 function independently, whereas site 2 functions synergistically with
      either site 3 or 4. Mobility shift assays indicate that all elements bind factors
      in the nuclear extracts of PC-3-M cells. Characterization of the sites show that
      site 1, though a positive element, is not E2F specific; sites 2 and 3 may contain
      an overlapping binding site for E2F and NF1; and site 4, which resides in intron
      1, is the only site shown to interact exclusively with E2F. These studies suggest
      that the overexpression of Op18 in PC-3-M cells is mediated predominantly through
      the E2F family of transcription factors.

PMID- 15474304
TI  - Translation termination in Arabidopsis thaliana: characterisation of three
      versions of release factor 1.
AB  - Translation termination is mediated in all eukaryotes by the two release factors
      eRF1 and eRF3. Most organisms have a single eRF1 gene, however, three isogenes of
      eRF1 are found in Arabidopsis thaliana. They have no introns in the coding region
      which may indicate that some are pseudogenes. However, each was expressed and
      able to rescue a temperature sensitive eRF1-mutant of Saccharomyces cerevisiae
      indicating functional redundancy in A. thaliana. While normally a highly accurate
      process, translation termination can be directed to fail by sequence elements
      within an messenger RNA (mRNA). Interestingly, a well-characterised readthrough
      element follows the stop codon in one of these three isogenes (designated eRF1
      1). This element was shown to be capable of inducing readthrough in an in vitro
      assay using a dual luciferase reporter, but surprisingly readthrough could not be
      detected using the complete gene context. The results highlight the diversity and
      duplication of genes within plant genomes, but also emphasize the conservation of
      the translation process across kingdoms.

PMID- 15474305
TI  - Reduction of adenovirus E1A mRNA by RNAi results in enhanced recombinant protein
      expression in transiently transfected HEK293 cells.
AB  - Human embryonic kidney 293 (HEK293) cells, a widely used host for large-scale
      transient expression of recombinant proteins, are transformed with the adenovirus
      E1A and E1B genes. Because the E1A proteins function as transcriptional
      activators or repressors, they may have a positive or negative effect on
      transient transgene expression in this cell line. Suspension cultures of HEK293
      EBNA (HEK293E) cells were co-transfected with a reporter plasmid expressing the
      GFP gene and a plasmid expressing a short hairpin RNA (shRNA) targeting the E1A
      mRNAs for degradation by RNA interference (RNAi). The presence of the shRNA in
      HEK293E cells reduced the steady state level of E1A mRNA up to 75% and increased
      transient GFP expression from either the elongation factor-1alpha (EF-1alpha)
      promoter or the human cytomegalovirus (HCMV) immediate early promoter up to
      twofold. E1A mRNA depletion also resulted in a twofold increase in transient
      expression of a recombinant IgG in both small- and large-scale suspension
      cultures when the IgG light and heavy chain genes were controlled by the EF
      1alpha promoter. Finally, transient IgG expression was enhanced 2.5-fold when the
      anti-E1A shRNA was expressed from the same vector as the IgG light chain gene.
      These results demonstrated that E1A has a negative effect on transient gene
      expression in HEK293E cells, and they established that RNAi can be used to
      enhance recombinant protein expression in mammalian cells.

PMID- 15474306
TI  - Human transcription factor Sp3: genomic structure, identification of a processed
      pseudogene, and transcript analysis.
AB  - The human transcription factor Sp3 has been widely studied at the translational
      level and has been described as a regulatory factor for a number of genes. Sp3 is
      currently characterized as a bifunctional transcription factor having the ability
      to behave as both an activator and/or a repressor in various promoter regions.
      Previous translational studies have attempted to determine the basis for these
      diverse functions with mostly contradictory evidence to date. Little data are
      available, however, concerning genomic structure, full-length cDNA, potential
      transcript variants, or location of translation initiation sites for the large
      isoform of the Sp3 gene. In this study, bacterial artificial chromosome (BAC)
      sequencing, reverse transcription-polymerase chain reaction (RT-PCR), genomic
      PCR, and database mining indicate that the Sp3 gene encompasses seven exons
      spanning more than 55 kb of genomic DNA on Chromosome 2. The 5' end of this
      sequence contains a large CpG island. This work also detected a processed
      pseudogene, psiSp3, located on Chromosome 13, spanning approximately 4.0 kb.
      Northern blot analysis detected three predominant transcripts at 4.0, 6.0 and 2.5
      kb. Sequence analysis indicated that alternative splicing of exon 3 allows for
      multiple transcripts of Sp3. Each sequenced transcript possesses three to five
      potential translation initiation sites. This diversity at the level of gene
      expression will likely be key to understanding the diverse functions of Sp3.

PMID- 15474307
TI  - Amino acid sequence of the Felis catus prion protein.
AB  - A new determination of the house cat (Felis catus) prion protein gene sequence
      (fPrnp), which has so far been subject of controversy, is reported. The newly
      determined fPrnp sequence is similar to dog (Canis familiaris) and mink (Mustela
      putorius) Prnp, but differs significantly from both fPrnp sequences that were
      previously deposited in the GenBank. Comparison of the canine and feline prion
      protein sequences suggests a set of amino acid replacements relative to bovine
      PrP that might relate to the observed different susceptibilities of the two
      species to TSE infection by ingestion of BSE-infected beef.

PMID- 15474309
TI  - Transcriptome of 3D7 and its gametocyte-less derivative F12 Plasmodium falciparum
      clones during erythrocytic development using a gene-specific microarray assigned
      to gene regulation, cell cycle and transcription factors.
AB  - During the complex life cycle of Plasmodium falciparum, through mosquito and
      human, the erythrocytic cycle is responsible for malarial disease and
      transmission. The regulation of events that occur during parasite development,
      such as proliferation and differentiation, implies a fine control of
      transcriptional activities that in turn governs the expression profiles of sets
      of genes. Pathways that underline gametocyte commitment are yet poorly understood
      even though kinases and transcription factors have been assumed to play a crucial
      role in this event. In order to understand the molecular mechanisms controlling
      the variation of gene expression profiles that might participate in early
      gametocytogenesis, the transcriptome of two clones, 3D7 and its gametocyte-less
      derivative F12, was compared at five time points of the erythrocytic asexual
      development. We have used a thematic DNA microarray containing 150 PCR fragments,
      representative of P. falciparum genes involved in signal transduction, cell cycle
      and transcriptional regulation. We identified several genes eliciting different
      expression profiles among which some implicated in gene regulation or encoding
      putative transcription factors. The differential expression of transcription
      factor and kinase transcripts observed in the two clones may enlighten genes that
      might have a role in impairment of the early gametocytogenesis of the F12 clone.

PMID- 15474308
TI  - Representation of an immune responsive gene family encoding fibrinogen-related
      proteins in the freshwater mollusc Biomphalaria glabrata, an intermediate host
      for Schistosoma mansoni.
AB  - Fibrinogen-related proteins (FREPs) are found in the hemolymph of the freshwater
      snail Biomphalaria glabrata, are up-regulated following exposure to digenetic
      trematode parasites, and bind to trematode larval surfaces, suggestive of a role
      in internal defense. Southern blot and degenerate-polymerase chain reaction (PCR)
      analyses were undertaken to better understand the diversity of the FREP-encoding
      gene family. Probes corresponding to the N-terminal IgSF domains of specific FREP
      gene subfamilies (FREPs 2, 3, 4, 7, 12 and 13) revealed between 1 to 8 loci per
      subfamily on Southern blots. Probes representing the relatively conserved C
      terminal fibrinogen domain of FREPs bound many sequences in Southern blots of
      genomic DNA from B. glabrata, and from two related gastropod species,
      Biomphalaria pfeifferi and Helisoma trivolvis. Using degenerate-PCR, we obtained
      42 unique fibrinogen-encoding sequences from 180 clones derived from a single
      individual of the M-line strain of B. glabrata, further supporting the notion of
      their abundant representation in the B. glabrata genome. The fibrinogen-encoding
      sequences of FREPs encoding one or two IgSF domains tended to separate into
      distinct clades, but bootstrap support for this separation was low. A novel
      category of fibrinogen-encoding sequence was also revealed. This study provides
      the approximate number of gene copies in several FREP subfamilies, confirms the
      existence of a diverse FREP gene family, reports additional unusual sequences
      encoding fibrinogen-like molecules, and provides further justification to explore
      the functional roles of FREPs in both B. glabrata and B. pfeifferi, both
      important intermediate hosts of the human pathogen, Schistosoma mansoni.

PMID- 15474310
TI  - Disruption of the mouse phospholipase C-beta1 gene in a beta-lactoglobulin
      transgenic line affects viability, growth, and fertility in mice.
AB  - A recessive insertional mutation was identified in one line of transgenic mice
      for the caprine beta-lactoglobulin (betaLG) gene. High mortality after birth, a
      significant reduction in postnatal growth and adult body size, changes in the
      morphometric features of the head, and infertility are the most prominent
      phenotypic traits of the mutant animals. Molecular cloning and sequencing of the
      transgene insertion site showed that 22 copies of the betaLG transgene are
      inserted in an intronic region of the phospholipase C-beta1 (PLC-beta1) gene,
      which plays a pivotal role in modulating different cellular functions. As a
      result of the insertional mutation (PLC-beta1(betaLG) mutation), a hybrid
      messenger RNA (mRNA) between the mouse PLC-beta1 and the goat betaLG genes is
      transcribed. The tissue-specific pattern of expression of this hybrid mRNA in PLC
      beta1(betaLG) homozygotes is equivalent to that of the endogenous PLC-beta1 mRNA
      in nontransgenic animals, which is reported for the first time in this species,
      but expression levels are significantly reduced. Although the hybrid PLCbeta1
      betaLG mRNA contains all the essential information to produce a PLCbeta1 protein
      that could be activated, this protein was not detected by Western blot. The PLC
      beta1(betaLG) mouse model described here represents a useful tool to investigate
      the role of the PLC-beta1 gene in the molecular mechanisms underlying growth and
      fertility.

PMID- 15474311
TI  - Comparative analysis of the human gimap gene cluster encoding a novel GTPase
      family.
AB  - There is a growing family of novel GTPases conserved among higher plants and
      vertebrates, abbreviated as AIG1, IAP, IMAP, and IAN, respectively. Here, we
      comparatively analyze the human gene family encoding GTPases of the immunity
      associated protein family recently re-termed GIMAP. Chromosome 7q36.1 contains,
      within 300 kb, a gimap gene cluster with seven functional genes and one
      pseudogene (hgimap3). The six genes hgimap1, hgimap2, hgimap4, hgimap5, hgimap6,
      and hgimap7 encode 33-46 kDa proteins with one GTP-binding domain, whereas
      hgimap8 encodes a very unusual 75-kDa protein with three GTP-binding domains. All
      hgimap genes except hgimap2 have orthologs in the mouse. Major expression sites
      of hgimap mRNAs are the spleen and lymph nodes, but also other organs such as
      muscle, heart, placenta, and digestive tract display detectable hgimap mRNA
      levels. The proteins hGIMAP4 and hGIMAP7 can be localized at ER and Golgi
      apparatus, but not in mitochondria, lysosomes and nuclei. All hgimap genes were
      expressed at very low levels-if at all-in diverse cancer cell lines. Our data
      support the view that the GIMAP proteins are involved in the control of cell
      survival not only in cells of the immune system as commonly anticipated.

PMID- 15474312
TI  - Identification and expression of a mouse muscle-specific CTL1 gene.
AB  - In this study, a mouse gene and cDNA encoding for a novel skeletal muscle
      specific choline transporter-like protein 1 (mCTL1) were identified and mCTL1
      mRNA and protein expression characterized. The mCTL1 cDNA is 2888-bp long;
      consisting of a 653-amino-acid open-reading frame, 8-11 putative transmembrane
      domains, three N-glycosylation sites and seven protein kinase C phosphorylation
      sites. The mCTL1 gene is localized to chromosome 4B2, at 182 kb in length, and
      encoded by 17 exons. Although the mCTL1 mRNA was expressed in several mouse
      tissues such as muscle, brain, heart and testis, the protein analyses of multiple
      tissues and membrane vesicles reveal that mCTL1 is exclusively expressed in
      skeletal muscle. Expression of His-tagged mCTL1 in Cos-7 cells produces an
      increase in saturable choline uptake that is sensitive to a Na(+)-ion gradient,
      ethanolamine and the Ca(2+)-channel blocker verapamil, and insensitive to low
      concentrations of hemicholinium-3.

PMID- 15474313
TI  - Tau gene (MAPT) sequence variation among primates.
AB  - Filamentous tau deposits are a defining feature of a number of human
      neurodegenerative diseases. Apes and monkeys have been reported to be
      differentially susceptible to developing tau pathology. Despite this, only little
      is known about the organisation and sequence of Tau from nonhuman primates. Here
      we have sequenced Tau exons 1-13, including flanking intronic regions, and the
      region in intron 9 that contains Saitohin in chimpanzees, gorillas, and gibbons.
      Partial sequences were obtained for cynomolgus macaque and green monkey.
      Chimpanzee brain tau was 100% identical to human tau. Identities were 99.5% for
      gorilla tau and 99.0% for gibbon tau. Chimpanzee DNA was polymorphic for a repeat
      in intron 9, which was present in human and gorilla tau, and for the nucleotide
      at position +29 of the intron that follows exon 10. As was the case of the other
      nonhuman primates examined, chimpanzee DNA was homozygous for nucleotides used to
      define the H2 haplotype in human Tau. These differences between human and
      chimpanzee Tau may contribute to the apparent resistance of chimpanzee brain to
      developing tau pathology. Sequencing of Saitohin revealed an intact open reading
      frame in chimpanzee and gorilla, but not in gibbon or macaque.

PMID- 15474314
TI  - Identification of a genomic fragment that directs hematopoietic-specific
      expression of Rac2 and analysis of the DNA methylation profile of the gene locus.
AB  - Rac2 is a Rho family GTPase expressed specifically in hematopoietic cells. The
      4.5 kb proximal Rac2 gene promoter exhibits strong but promiscuous activity
      following either transient or stable transfection into tissue culture cells,
      indicating that additional cis-elements are required to silence Rac2 expression
      in non-hematopoietic cells. A bacterial artificial chromosome (BAC) containing
      the human Rac2 gene, including as little as 1.6 kb of upstream and 8 kb of
      downstream sequence, exhibits hematopoietic-restricted expression in transgenic
      mice. The Rac2 genomic locus exhibits distinct patterns of DNA methylation in
      expressing versus non-expressing cells. Cells that lack Rac2 expression exhibit
      increased cytosine methylation in the sequences flanking the gene, whereas cells
      that express Rac2 exhibit increased cytosine methylation within the body of the
      Rac2 gene. Treatment of non-expressing cells with the DNA methyltransferase
      (DNMT) inhibitor 5-aza-2'-deoxycytidine reduces cytosine methylation of the Rac2
      gene locus and is sufficient to induce Rac2 gene expression. Conversely,
      treatment with the histone deacetylase (HDAC) inhibitor trichostatin A fails to
      induce Rac2 gene expression. These findings define a genomic fragment sufficient
      to direct hematopoietic-specific expression of Rac2, and reveal the importance of
      cytosine methylation in the repression of Rac2 expression in non-hematopoietic
      cells.

PMID- 15474315
TI  - Bacteremia in a patient with colonic carcinoma caused by a novel Sedimentibacter
      species: Sedimentibacter hongkongensis sp. nov.
AB  - A bacterium was isolated from the blood culture of a 91-year-old patient with
      colonic carcinoma. The cells were strict anaerobic, motile, Gram-negative,
      sporulating, straight, or slightly curved rods. The bacterium grew on agar using
      the BACTEC anaerobic blood culture broth or buffered charcoal yeast extract agar
      as pinpoint colonies after 72 h of incubation at 37 degrees C in anaerobic
      conditions. It did not grow on blood agar, chocolate agar, MacConkey agar,
      nutrient agar or broth, brain heart infusion agar or broth, Brucella agar, or
      cooked meat medium. It produces catalase but not cytochrome oxidase. 16S rRNA
      gene sequencing and phylogenetic analysis showed that it is closely related to
      Sedimentibacter hydroxybenzoicus and Sedimentibacter saalensis, with 10.5% and
      11.9% differences between the 16S rRNA gene sequence of the bacterium and those
      of S. hydroxybenzoicus and S. saalensis respectively. A new species,
      Sedimentibacter hongkongenesis sp. nov., is proposed, for which HKU2(T) is the
      type strain.

PMID- 15474316
TI  - The epidemiology of self-reported diarrhea in operations Iraqi freedom and
      enduring freedom.
AB  - Diarrhea remains a potential cause of compromised military effectiveness. To
      assess diarrhea rates and mission impact in operations in Iraq and Afghanistan, a
      survey was administered to soldiers participating in the "Rest and Recuperation"
      program in Doha, Qatar. Between October and December 2003, 2,389 volunteers
      completed a questionnaire designed to assess the occurrence and impact of
      diarrhea. The median length of deployment was 7.2 months, 70% reported at least
      one episode, and 56% had multiple episodes of diarrhea. Overall, 43% reported
      decreased job performance for a median of 2 days, and 17% reported being on bed
      rest for a median of 2 days. While this survey showed high rates of diarrhea
      associated with decreased operational effectiveness, the results are consistent
      with prior military operations in this region. Further research is needed to
      develop better methods for illness prevention and its minimization on operational
      impact.

PMID- 15474317
TI  - Pharmacokinetics, safety, and tolerability of ascending single intravenous doses
      of oritavancin administered to healthy human subjects.
AB  - Oritavancin (LY333328 diphosphate) is a novel glycopeptide antimicrobial agent
      with potent microbiological activity in vitro against Gram-positive bacteria. A
      single-dose, open-label, noncontrolled, dose-escalation study in 11 healthy human
      subjects was carried out to evaluate the safety and pharmacokinetics of
      oritavancin. One subject at each dose level received a single intravenous dose of
      0.02, 0.03, 0.05, 0.08, 0.125, 0.20, and 0.325 mg/kg infused over 1 hour and four
      subjects each received a single-dose of 0.5 mg/kg. Safety and tolerability were
      evaluated by monitoring adverse events and laboratory parameters. Oritavancin
      pharmacokinetics were assessed by blood, urine, and fecal sampling. The plasma
      concentrations of oritavancin after the end of infusion followed a
      multiexponential decline over a 2-week period. Median (range) C(max) for the 0.5
      mg/kg dose group was 6.5 (4.7-7.6) microg/mL. In every subject, plasma
      concentrations declined to < or =10% of the C(max) within 24 hours. Following a
      short, constant-rate infusion, the pharmacokinetics of oritavancin were linear
      across a total dose range from 3.66-44.6 mg. Renal clearance was approximately
      0.457 mL/min. The mean (range) plasma terminal half-life of oritavancin was 195.4
      (135.8-273.8) hours across all dose levels from 0.05-0.5 mg/kg. Less than 5% and
      1% of administered drug were recovered in the urine and feces, respectively,
      after 7 days. This first time in man evaluation of oritavancin revealed that
      single doses of oritavancin of up to and including 0.5 mg/kg were safe and well
      tolerated. Although no clinically relevant changes in renal, hepatic and
      hematologic indices from baseline were observed, five subjects did manifest
      asymptomatic and transient elevations of hepatic transaminase concentrations.
      Because this study was not placebo-controlled and enrolled a small number of
      subjects, the safety and pharmacokinetic profiles of oritavancin need to be
      confirmed in additional studies.

PMID- 15474318
TI  - Rapid, automated, nonradiometric susceptibility testing of Mycobacterium
      tuberculosis complex to four first-line antituberculous drugs used in standard
      short-course chemotherapy.
AB  - The increasing prevalence of drug-resistant tuberculosis necessitates rapid and
      accurate susceptibility testing. The nonradiometric BACTEC Mycobacteria Growth
      Indicator Tube 960 (MGIT) system for susceptibility testing was evaluated on 222
      clinical Mycobacterium tuberculosis complex isolates for isoniazid, rifampin, and
      ethambutol. Fifty-seven of the isolates were tested for pyrazinamide. Results
      were compared to those of radiometric BACTEC 460 system and discrepancies were
      resolved by the agar proportion method. We found an overall agreement of 99.0%
      for isoniazid, 99.5% for rifampin, 98.2% for ethambutol, and 100% for
      pyrazinamide. After resolution of discrepancies, MGIT yielded no false
      susceptibility for rifampin and isoniazid. Although turnaround times were
      comparable, MGIT provides an advantage as inoculation can be done on any weekday
      as the growth is monitored automatically. The automated MGIT system is a rapid
      and reliable alternative for susceptibility testing of M. tuberculosis complex to
      first-line drugs.

PMID- 15474319
TI  - New method for detection of Mycobacterium tuberculosis Direct Test inhibitors in
      clinical specimens.
AB  - Existing protocols for the detection of Mycobacterium tuberculosis Direct Test
      (MDT) inhibitors require substantial quantities of specimen and cannot
      distinguish Mycobacterium tuberculosis complex from other mycobacteria if
      inhibitors are present. We describe a preliminary evaluation of a simple and
      practical protocol for MTD inhibitor testing that circumvents these difficulties.

PMID- 15474320
TI  - Clinical evaluation of a dried commercially prepared microdilution panel for
      antifungal susceptibility testing of five antifungal agents against Candida spp.
      and Cryptococcus neoformans.
AB  - A commercially prepared dried-broth microdilution panel (Sensititre, TREK
      Diagnostic Systems, Cleveland, OH) was compared with a reference frozen-broth
      microdilution panel for antifungal susceptibility testing of 728 clinical
      isolates of Candida spp. and 98 clinical isolates of Cryptococcus neoformans. The
      antifungal agents tested were amphotericin B, fluconazole, 5-fluorocytosine
      (5FC), itraconazole, and voriconazole. Microdilution testing was performed
      according to NCCLS recommendations. Minimum inhibitory concentration (MIC)
      endpoints were read visually after 48 hours of incubation (72 hours for C.
      neoformans) and were assessed independently for each microdilution panel.
      Discrepancies among MIC endpoints of no more than 2 log(2) dilutions were used to
      calculate the percentage of agreement. Overall levels of agreement between the
      study and reference panels were 98% for Candida spp. and 93% for C. neoformans.
      The agreement for each antifungal agent ranged from 96.6% for voriconazole to
      99.4% for amphotericin B. The TREK dried microdilution panel appears to be a
      viable alternative to frozen-broth microdilution panels for testing of Candida
      spp. and C. neoformans.

PMID- 15474321
TI  - Utility of real-time antifungal susceptibility testing for fluconazole in the
      treatment of candidemia.
AB  - Our study prospectively examined the use of real-time antifungal susceptibility
      testing among 119 patients with candidemia at a large tertiary university medical
      center over a 1-year period. Susceptibility results to fluconazole were reported
      to physicians a mean of 5.1 days after the initial positive blood culture for
      Candida. Physicians believed that receiving antifungal susceptibility testing
      results was helpful and not infrequently altered therapy on the basis of results.
      Outcomes, including mortality and resolution of infection, among 20 (17%)
      patients with fluconazole-resistant and fluconazole-susceptible dose-dependent
      isolates were relatively poor compared to those among patients with fluconazole
      susceptible isolates, but probably reflect severity of illness. Routine
      susceptibility testing as an adjunct to the treatment of candidemia has
      significant potential and warrants further study.

PMID- 15474322
TI  - Clinical glycopeptide-intermediate staphylococci tested against arbekacin,
      daptomycin, and tigecycline.
AB  - We examined the activity of arbekacin, daptomycin, tigecycline, and vancomycin
      against various Staphylococci isolates with glycopeptide-intermediate (n = 25)
      and heterogeneous susceptibilities (n = 22) (GISS and hGISS). The minimum
      inhibitory concentrations (MIC) of each antimicrobial was evaluated in time-kill
      experiments by using 4 randomly selected GISS isolates tested at 2 and 4 times
      their respective MIC. The MIC(90) microg/mL ranges for arbekacin, daptomycin,
      tigecycline, and vancomycin were 2 (0.25-4), 1 (0.0625-2), 0.5 (0.0625-2), and 8
      (4-8), respectively. Time kill at 2 times the MIC demonstrated a mean log(10)
      colony forming units (CFU)/mL change of -2.98 +/- 0.708, -3.6 +/- 0.509, -2.48 +/
      0.647, and +1.14 +/- 0.1 arbekacin, daptomycin, tigecycline, and vancomycin,
      respectively. At 4 times the MIC, significant activity for all compounds was
      noted with a log(10) CFU/mL decrease range from 3.68 to 2.74 +/- 0.66. Overall,
      all the antimicrobials tested (with the exception of vancomycin) exhibited
      significant in vitro activity against GISS. These compounds may offer therapeutic
      options for the treatment of GISS.

PMID- 15474323
TI  - High incidence of extended-spectrum beta-lactamases among outpatient clinical
      isolates of Escherichia coli: a phenotypic assessment of NCCLS guidelines and a
      commercial method.
AB  - The production of extended-spectrum beta-lactamases (ESBLs) among 357 clinical
      isolates of Escherichia coli and 175 of Klebsiella spp. was studied using both
      the National Committee for Clinical Laboratory Standards disk diffusion method
      and the semiautomated Wider system. We highlight the predominance of E. coli (50,
      92.6%) among positive samples and the largely outpatient origin of these (40,
      80%), including 39 samples of urine (97.5%) and one of urethral exudate. There
      were only four ESBL-producing isolates of Klebsiella spp. (7.4%), and three were
      in outpatient urine samples (75%, 2 K. oxytoca and 1 K. pneumoniae). The positive
      and negative predictive values for the Wider system were 81% and 98.5%,
      respectively. We stress the high incidence of ESBL in our setting, the
      predominance of cases in the outpatient setting, and the acceptable detection of
      ESBL by means of the Wider system in E. coli and Klebsiella spp.

PMID- 15474324
TI  - Fatal Nocardia farcinica bacteremia in a patient with lung cancer.
AB  - Nocardia farcinica is an emerging pathogen in immunocompromised patients,
      accounting for approximately 20% of Nocardia clinical isolates in various
      countries. A case of fatal N. farcinica bacteremia in a 52-year-old man with lung
      cancer is described. He was admitted with severe respiratory distress, and
      despite the early onset of empirical antibiotic treatment, he failed to respond
      and died of septic shock 24 hours later. N. farcinica was isolated from blood
      cultures obtained at hospital admission and was identified by conventional
      methods. Strain identification was confirmed by nucleotide sequencing of the 16S
      rRNA gene. N. farcinica bacteremia is a life-threatening infection. Because of
      the actinomycete's highly-resistant antibiotic profile, early identification and
      antibiotic susceptibility testing are necessary to improve the chances of
      survival.

PMID- 15474325
TI  - Legionella maceachernii pneumonia in a patient with HIV infection.
AB  - We report a case of fatal Legionella maceachernii pneumonia in a 49 year-old man
      with HIV infection and review the 3 previous reported cases, all of which
      occurred in individuals with underlying immune defects. Infection with L.
      maceachernii was attributable to the deaths of all cases. Issues related to the
      clinical aspects, laboratory identification of this unusual species, and
      detection of Legionnaires' diseases are discussed.

PMID- 15474326
TI  - Classification of Giardia duodenalis parasites in Turkey into groups A and B
      using restriction fragment length polymorphism.
AB  - PCR-RFLP (restriction fragment length polymorphism) analysis was used to
      determine the relation of Giardia duodenalis Groups A and B. Of these, 17 (85%)
      were found as Group A in symptomatic cases; 22 (92%) were Group B in asymptomatic
      cases by using PCR-RFLP (p < 0.001). Interestingly, 5 (83%) were Group A in
      examination of endoscopy aspirates of symptomatic cases, as 5 (83%) were Group B
      in asymptomatic cases.

PMID- 15474327
TI  - Antibiotic resistance may affect alkali decontamination of specimens containing
      mycobacteria.
AB  - The influence of genetic modification on the decontamination process of
      mycobacteria was investigated using a wild type Mycobacterium bovis BCG Pasteur
      and its isogenic mutant strain. The result showed that the killing effect of
      sodium hydroxide (NaOH) progressively increased with prolonged incubation (up to
      20 minutes), and the deteriorating effect of NaOH was more severe on the
      genetically modified strain.

PMID- 15474329
TI  - The vascular endothelial growth factor family and its receptors.
AB  - This article focuses on describing the biology of vascular endothelial growth
      factor (VEGF) and its receptors as well as the regulation of their expression. A
      thorough understanding of the VEGF system is paramount in optimizing
      antiangiogenic therapies as a component of antineoplastic regimens.

PMID- 15474330
TI  - The relationship between the tumor physiologic microenvironment and angiogenesis.
AB  - This article examines the pathophysiology of tumors, with an emphasis on how
      these features influence angiogenesis in tumors.

PMID- 15474331
TI  - The role of integrins in tumor angiogenesis.
AB  - Integrins are cell adhesion molecules that play an important role in the
      regulation of angiogenesis. In this overview, the vascular integrins and their
      mechanisms of action are outlined. Integrins have been evaluated in preclinical
      and clinical studies for the treatment of cancer and as diagnostic markers of
      angiogenesis. Furthermore, integrins are the basis for targeted therapy for solid
      tumors and novel imaging techniques to assess the angiogenic response of tumors.

PMID- 15474332
TI  - Epidermal growth factor receptor in tumor angiogenesis.
AB  - This article focuses on the preclinical evidence for activation of the epidermal
      growth factor receptor (EGFR) in promoting angiogenesis and the efficacy of anti
      EGFR agents in inhibiting angiogenesis and tumor growth.

PMID- 15474333
TI  - Therapeutic strategies that selectively target and disrupt established tumor
      vasculature.
AB  - This articles discusses therapeutic strategies that selectively target and
      disrupt established tumor vasculature.

PMID- 15474334
TI  - Improving tumor response to radiotherapy by targeting angiogenesis signaling
      pathways.
AB  - Radiotherapy is one of the most widely used treatments for cancer; however, the
      development of tumor radioresistance is an ongoing problem. Agents that target
      tumor angiogenesis are being used in combination with radiotherapy to improve the
      therapeutic index without a clear understanding of how these agents may affect
      radiosensitization. This article discusses recently published studies that may
      shed some light on the underlying signaling mechanisms that are involved in the
      interactions of antiangiogenic agents with ionizing radiation.

PMID- 15474335
TI  - Angiogenesis and lymphangiogenesis of skin cancers.
AB  - Malignant melanomas of the skin are distinguished by their propensity for early
      metastatic spread by way of lymphatic vessels to regional lymph nodes; lymph node
      metastasis is a major determinant for the staging and clinical management of
      melanoma. The importance of tumor-induced lymphangiogenesis for lymphatic
      melanoma spread is unclear, however. Recent experimental and clinical evidence
      strongly suggest that active lymphangiogenesis is induced by many tumor types,
      including cutaneous melanoma, and that it plays an important role in lymphatic
      tumor dissemination. The extent of tumor-associated lymphangiogenesis can serve
      as a powerful prognostic tool for the evaluation of primary cutaneous melanomas.
      A better molecular understanding of the lymphatic system may provide new insights
      into the biology of tumor metastasis and may provide novel prognostic and
      therapeutic tools in metastatic disease.

PMID- 15474336
TI  - Breast cancer: the role of angiogenesis and antiangiogenic therapy.
AB  - Angiogenesis plays a role in breast cancer development. Preclinical and clinical
      evidence is reviewed. Development of targeted antiangiogenic agents provides new
      challenges to clinical trial design. Current antiangiogenic therapy with
      traditional agents and novel agents are classified and reviewed.

PMID- 15474337
TI  - Angiogenesis in colorectal cancer: therapeutic implications and future
      directions.
AB  - This article discusses the therapeutic implications and future directions of
      angiogenesis in colorectal cancer.

PMID- 15474338
TI  - Angiogenesis inhibitors in the treatment of small cell and non-small cell lung
      cancer.
AB  - Angiogenesis is believed to play a critical role in cancer; however,
      antiangiogenic therapy has not been demonstrated to improve the survival of
      patients who have lung cancer. In this article, the evidence that supports a role
      for angiogenesis in the pathogenesis of lung cancer, trials of antiangiogenic
      agents in lung cancer performed to date, and the lessons learned from these
      studies are discussed.

PMID- 15474339
TI  - Renal cell carcinoma: rationale and development of therapeutic inhibitors of
      angiogenesis.
AB  - Inhibition of tumor angiogenesis is a promising therapeutic approach to treat
      cancer; translation of this concept into clinical practice requires an
      understanding of the molecular events that are responsible for the development of
      tumor vasculature. Renal cell carcinoma is characterized by the frequent loss of
      the von Hippel-Lindau tumor suppressor gene which results in the loss of one of
      the critical mechanisms for regulating the level of hypoxia inducible factor 1
      and leads to the overproduction of vascular endothelial growth factor (VEGF) by
      the tumor cell. Therapeutic strategies to inhibit the function of these important
      pathways have been effective in preventing tumor angiogenesis in preclinical
      models of kidney cancer, and more recently, in the clinical setting. Strategies
      to treat renal cell carcinoma with agents that are designed to prevent
      angiogenesis have included interruption of the VEGF signaling pathway, mimics of
      endogenous angiogenesis inhibitors, prevention of destruction of the basement
      membrane, and direct inhibition of endothelial cells by a variety of agents with
      complex, novel, or undetermined mechanisms. Recent clinical studies of
      bevacizumab, the first anti-VEGF agent to be marketed for the treatment of
      cancer, have provided proof for the concept that these strategies can lead to
      tangible benefits for patients who have advanced renal cell carcinoma and likely
      will be applicable broadly to the treatment of cancer.

PMID- 15474340
TI  - Antiangiogenic therapy for primary and metastatic brain tumors.
AB  - We first provide the theoretic foundation of antiangiogenic therapy by describing
      the biology of angiogenesis as it applies to brain tumors. We then outline
      experimental antiangiogenic therapies that are being applied preclinically to
      brain tumors, as well as published clinical trial data and ongoing clinical
      trials in patients. Primary and metastatic brain tumors are covered, although
      there is far less exploration in the literature of brain metastases.

PMID- 15474341
TI  - The role of imaging in the clinical development of antiangiogenic agents.
AB  - Early clinical development of novel antiangiogenesis agents is hampered by the
      fact that classic response end points are unlikely to be relevant and there is a
      lack of validated surrogate markers of efficacy. Toxicity-based decisions for
      dose setting and tumor size measurements by standard imaging probably are not be
      applicable. Because these agents modify a multitude of biologic processes that
      may cause early measurable effects, there is great interest in developing imaging
      tests that are sensitive to changes in tissue function. This article discusses
      the development of such "functional" clinical imaging and attempts to address the
      questions that are being asked of imaging departments by oncologists and
      pharmaceutical companies.

PMID- 15474342
TI  - Learning environments.

PMID- 15474343
TI  - Detecting pain in people with an intellectual disability.
AB  - The assessment of pain in a person with an intellectual disability (ID) is often
      a difficult undertaking complicated by idiosyncratic reactions or vague
      descriptions. The person with an ID may also be unable to verbally communicate
      their discomfort. For the carer who knows the individual with an ID, knowing how
      they respond to painful stimuli assists the carer to detect new instances of
      pain. The emergency nurse is unlikely to have met the person with an ID and
      therefore detecting pain by observing behaviour or using self-report measures is
      unlikely to succeed. There have been some attempts to categorize behavioural
      responses to pain by people with an ID, however, they have not been developed
      into a useful assessment tool. Emergency nurses must therefore rely on the person
      who knows the person with an ID.

PMID- 15474344
TI  - Therapeutic communication part 2: strategies that can enhance the quality of the
      emergency care consultation.
AB  - Therapeutic, patient-centred communication as well as being desirable in its own
      right may also have the potential to improve satisfaction, health outcomes and
      change health behaviours in Emergency Care. This paper, the second of two,
      identifies from a substantive literature review five specific communication
      strategies that, when employed in an Emergency Care consultation, could
      significantly enhance its therapeutic potential. The five strategies:
      questioning, listening and noticing, communicating empathy, establishing and
      incorporating the patient's cares and concerns and concluding the consultation
      have been derived from the purposeful selection and analysis of communication
      research between 1990 and 2002.

PMID- 15474345
TI  - Care for female survivors of child sexual abuse in emergency departments.
AB  - INTRODUCTION: The health impact of child sexual abuse (CSA) continues into
      adulthood with such problems as depression, self-harm, suicide attempts; stress
      related disorders and addictions implicated. Emergency nurses can facilitate
      early intervention and direct people to appropriate help if they recognise the
      CSA survivor's 'common story' described in this paper. METHODS: Findings come
      from an on-going participatory action research program with women survivors of
      CSA aiming to build personal capacity for women and organizational capacity for
      service providers. Data collected by 1:1 interviews and fortnightly group
      meetings are transcribed, analysed and fed back to the women (n11) and service
      providers (n25) for reflection and action. RESULTS: Recommendations include
      increasing staff awareness of impact of CSA; creating a culture of privacy and
      confidentiality that promotes safe disclosure; advocating sensitive responses;
      promoting client driven interactions/interventions that allow women to control
      potentially intrusive procedures; examining personal qualities of staff that
      assist client satisfaction; and provision of literature, web sites and referral
      protocols identifying professional support and self-help resources, etc.
      CONCLUSION: This paper presents practical responses generated by women survivors
      of CSA to improve emergency care and reduce return visits for this concealed and
      needy client group.

PMID- 15474346
TI  - Guilt, shame and need for a container: a study of post-traumatic stress among
      ambulance personnel.
AB  - Post-traumatic stress symptoms among ambulance personnel are regarded as a
      natural behaviour and reaction to working with the severely injured, suicides,
      injured children and dead people. The findings show that post-traumatic stress
      symptoms, guilt, shame and self-reproach are common after duty-related traumatic
      events. To handle these overwhelming feelings it is necessary to talk about them
      with fellow workers, friends or family members. By using another person as a
      container it is possible to internalise the traumatic experience. Poor and un
      emphatic behaviour towards a patient and their relatives can have its origin in
      untreated traumatic experiences. Personnel in ambulance organisations who perform
      defusing, debriefing and counselling have to be informed of the importance that
      the roll of guilt and shame may play in the developing of post-traumatic stress
      symptoms.

PMID- 15474347
TI  - Nurses' clinical decision-making regarding the management of pain.
AB  - Effective pain management remains an elusive goal within the profession of
      nursing. While considerable improvement has occurred, patients continue to
      experience inappropriate levels of pain. To date, research has focused on
      objective factors that influence pain management. Few studies have examined
      attitudinal factors that may influence nurses' decision-making. This quasi
      experiment was based on preliminary data showing that nurses' preconceived
      notions regarding certain patient groups influenced their management of pain. An
      intervention was tested for its' effect on nurses' preconceived notions regarding
      specific patient groups. A significant difference in a positive direction was
      found. Nurses were more willing to spend time and energy managing pain across all
      patient groups following the intervention.

PMID- 15474348
TI  - Reliability and validity of the Toowoomba adult trauma triage tool: a Queensland,
      Australia study.
AB  - INTRODUCTION: In Australia a nationally adopted five tiered triage scale called
      the Australasian triage scale (ATS) is used for the purpose of differentiating
      patient acuity levels for all patients that present to an emergency department
      (ED). The scale was formulated with the aim of promoting a standardized approach
      to triage. Numerous studies now suggest that the ATS has not been successful in
      achieving this intention. The Toowoomba adult trauma triage tool (TATTT) seeks to
      address this deficiency by providing an evidence based, reproducible, reliable
      and valid method of triage categorisation, albeit in a select group of patients.
      METHOD: Ten triage nurses from Toowoomba health service (THS) and five from
      Princess Alexandra Hospital in Queensland, Australia were enrolled in the study.
      Each participant rated five written simulations before receiving training in the
      TATTT. Each participant then rated nine written scenarios, five simulated
      scenarios on video and one computer simulated scenario with the TATTT. Parallel
      triaging of actual adult injury based presentations to THS ED was also
      undertaken. RESULTS: The overall percentage agreement for all simulations for
      which data were available was 87%. The overall kappa statistic was 0.82 with a
      95% confidence interval from 0.76 to 0.88. The overall percentage agreement
      between the triage category assigned using existing triage practices and the
      triage category assigned by the TATTT was approximately 47% with an estimated
      kappa of kappa(') = 0.19 (95% confidence interval [-0.02,0.40]). CONCLUSION:
      Evidence from this study suggests that the TATTT provides systematically
      different results compared to current triage practices utilising the ATS. This
      provided evidence that triage practices did not reflect current evidence or
      available descriptors. Additionally TATTT has greater reliability than current
      triage practices.

PMID- 15474350
TI  - Alpha-synuclein and transgenic mouse models.
AB  - Identified as the cause of some familial forms of Parkinson disease (PD) and as
      one of the major component of Lewy bodies, alpha-synuclein (alpha-syn) became the
      molecular hallmark of several neurodegenerative conditions now designated as
      synucleinopathies. Transgenic models have been generated to elucidate its
      physiological and pathologic roles. Although none of the lines created display
      dopaminergic neuronal death in the substantia nigra, the models recapitulate some
      features of synucleinopathies and are useful to study the potential pathogenic
      role of alpha-synuclein and its molecular partners. This review describes the
      different alpha-synuclein transgenic models, their clinical relevance to
      synucleinopathies, and their further utilization to understand the disease
      process.

PMID- 15474351
TI  - Genes, environment, and susceptibility to multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic disease of the central nervous system
      affecting young adults and thus representing a major burden also for their
      families and communities. The etiology of MS is obscure and its pathogenesis is
      yet incompletely depicted. Increased evidences indicate a strong genetic
      contribution to MS susceptibility, although others support the view that it is
      also influenced by environmental factors, possibly related to still unidentified
      pathogens. MS appears to be more heterogeneous than previously believed at the
      immunological level, and new pathological studies indicate a series of subset of
      conditions under the common denominator MS. The use of genetically homogeneous
      and geographically isolated populations at high MS risk, such as that of
      Sardinia, insular Italy, becomes in principle a vital requirement to reduce
      biological variables and the intrinsic complexity of the disease. This review
      will focus on recent findings on the peculiarity of Sardinian MS concerning
      epidemiological, genetic, and environmental aspects. Epidemiological studies
      reveal a clear heterogeneous distribution of MS cases in the Northern province of
      Sassari which may not be uniquely assigned to genetic variations. Furthermore, a
      different immunogenetic profile, including the association with other
      immunomediated diseases, and a progressive change in clinical phenotype,
      including age at onset, are present in this island which gives us unexpected
      variations at the level of patients' cohort and territorial distribution,
      especially when the northern province is compared to the southern one. This
      renders MS etiopathogenesis more complex than formerly thought even in this
      selected and genetically stable population.

PMID- 15474352
TI  - The alteration of calcium homeostasis in adult dystrophic mdx muscle fibers is
      worsened by a chronic exercise in vivo.
AB  - Chronic exercise in vivo aggravates dystrophy in mdx mice. Calcium homeostasis
      was evaluated ex vivo by micro-spectrofluorometry on tendon-to-tendon dissected
      extensor digitorum longus (EDL) muscle fibers. Resting cytosolic calcium
      ([Ca2+]i) and sarcolemmal permeability through Gd3+ -sensitive mechanosensitive
      calcium (MsCa) channel were significantly higher in mdx vs. wild-type fibers. The
      exercise further enhanced [Ca2+]i in mdx fibers and increased sarcolemmal
      permeability by activating nifedipine-sensitive leak calcium channels. The two
      genotypes did not differ in caffeine sensitivity and in the excitation-calcium
      release (ECaR) coupling mechanism by K+ depolarization. The exercise produced a
      similar adaptation of activation curve of ECaR and of sensitivity to caffeine.
      However, the inactivation of ECaR of mdx fibers did not adapt to exercise. No
      fiber phenotype transition occurred in exercised muscle. We provide the first
      evidence that an in vivo exercise worsens the impaired calcium homeostasis of
      dystrophic fibers, supporting the role of enhanced calcium entrance in dystrophic
      progression.

PMID- 15474353
TI  - Natively unfolded tubulin polymerization promoting protein TPPP/p25 is a common
      marker of alpha-synucleinopathies.
AB  - The novel basic, heat-stable tubulin polymerization promoting protein TPPP/p25 is
      associated with microtubules in vitro and can induce the formation of aberrant
      microtubule assemblies. We show by 1H-NMR spectroscopy that TPPP/p25 is natively
      unfolded. Antisera against peptide 186GKGKAGRVDLVDESG200NH2 (186-200) are highly
      specific to TPPP/p25. Immunohistochemistry and confocal microscopy demonstrates
      that TPPP/p25 is enriched in filamentous alpha-synuclein bearing Lewy bodies of
      Parkinson's (PD) and diffuse Lewy body disease (DLBD), as well as glial
      inclusions of multiple system atrophy (MSA). There is a correlation between
      TPPP/p25 and alpha-synuclein immunoreactivity in Western blot. In contrast,
      TPPP/p25 is not associated with abnormally phosphorylated tau in various
      inclusions of Pick's disease (PiD), progressive supranuclear palsy (PSP), and
      corticobasal degeneration (CBD). However, electron microscopy confirms clusters
      of TPPP/p25 immunoreactivity along filaments of unstructured but not compact
      neurofibrillary tangles in Alzheimer's disease (AD). TPPP/p25 seems to be a novel
      marker of alpha-synucleinopathies.

PMID- 15474354
TI  - Fibroblast growth factor-20 promotes the differentiation of Nurr1-overexpressing
      neural stem cells into tyrosine hydroxylase-positive neurons.
AB  - Stem cells are currently considered as alternative cell resources for restorative
      transplantation strategies in Parkinson's disease. However, the mechanisms that
      induce differentiation of a stem cell toward the dopaminergic phenotype are still
      partly unknown thus hampering the production of dopaminergic neurons from stem
      cells. In the past, FGF-20 has been found to promote the survival of ventral
      mesencephalic (VM) dopaminergic (DA) neurons in culture. We hereby provide
      evidence that FGF-20, a growth factor of the FGF family, is expressed in the
      adult and 6-OHDA-lesioned striatum and substantia nigra, but is not expressed by
      VM glia or DA neurons, suggesting that FGF-20 may work on DA neurons in a
      paracrine- or target-derived manner. We also found that co-culture of Nurr1-NSCs
      with Schwann cells overexpressing FGF-20 induced the acquisition of a neuronal
      morphology by the NSCs and the expression of tyrosine hydroxylase (TH) as
      assessed by immunocytochemistry, cell ELISA, and Western blot analysis. RT-PCR
      showed, that both, Schwann cells and Nurr1-NSCs (differentiated or not),
      expressed the FGF-1 receptor suggesting that both direct and indirect actions of
      FGF-20 are possible. We show that differentiated Nurr1 cells retained both
      neuronal morphology and TH expression after transplantation into the striatum of
      6-OHDA-lesioned postnatal or adult rats, but that neuritogenesis was only
      observed after postnatal grafts. Thus, our results suggest that FGF-20 promotes
      the differentiation of Nurr1-NSCs into TH-positive neurons and that additional
      factors are required for the efficient differentiation of DA neurons in the adult
      brain.

PMID- 15474355
TI  - IL-12p35 deficiency alleviates kainic acid-induced hippocampal neurodegeneration
      in C57BL/6 mice.
AB  - The role of IL-12 in excitotoxic neurodegeneration of brain is largely unknown.
      To address this issue, we used the model of kainic acid (KA)-induced hippocampal
      injury in IL-12p35 knockout (KO) mice, a well-characterized model for human
      neurodegenerative diseases. After KA treatment, hippocampal neurodegeneration was
      significantly less severe in the IL-12p35 KO mice than in wild-type mice as
      demonstrated by reduced pathological changes and astrogliosis. One day after KA
      treatment, levels of F4/80 and CD86 expression on microglia were significantly
      lower in IL-12p35 KO mice than in wild-type mice analyzed by flow cytometry,
      indicating that IL-12p35 deficiency resulted in lower levels of microglial
      activation. Five days after KA treatment, CD86 expression on microglia of wild
      type mice was still higher, whereas F4/80 expression in wild-type mice decreased
      and was similar to that in IL-12p35 KO mice. Because microglial activation is
      necessary for KA-induced neurodegeneration, the lower level of microglial
      activation in the absence of IL-12p35 may alleviate hippocampal injury in KO
      mice. In summary, this study indicates that IL-12 may play a critical role in
      excitotoxin-induced brain injury.

PMID- 15474356
TI  - Adenoviral transfer of the heme oxygenase-1 gene protects striatal astrocytes
      from heme-mediated oxidative injury.
AB  - Heme oxygenase-1 (HO-1) is induced in the CNS after hemorrhage, and may have an
      effect on injury to surrounding tissue. Hemin, the preferred substrate of HO, is
      a neurotoxin that is present in intracranial hematomas. In a prior study, we
      observed that HO inhibitors increased the vulnerability of cultured cortical
      astrocytes to heme-mediated oxidative injury. To investigate the effect of HO
      more specifically, we used an adenoviral vector encoding the human HO-1 gene to
      specifically increase HO-1 expression. Incubation with 100 MOI of the HO-1
      adenovirus (Adv-HHO-1) for 24 h increased both HO-1 protein and HO activity; a
      control adenovirus lacking the HO-1 gene had no effect. Using a DNA probe that
      was specific for human HO-1, 80.5 +/- 7.2% of astrocytes were observed to be
      infected by in situ hybridization. The cell death produced by 30-60 microM hemin
      was significantly reduced by pretreatment with 100 MOI Adv-HHO-1, as assessed by
      LDH release, propidium iodide exclusion, and MTT reduction assay. The threefold
      increase in cell protein oxidation produced by hemin was also attenuated in
      cultures pretreated with Adv-HHO-1. These results support the hypothesis that HO
      1 protects astrocytes from heme-mediated oxidative injury. Specifically
      increasing astrocytic HO-1 by gene transfer may have a beneficial effect on
      hemorrhagic CNS injury.

PMID- 15474357
TI  - Differential alterations in the expression and activity of matrix
      metalloproteinases 2 and 9 after transient cerebral ischemia in mice.
AB  - Abnormal expression and activity of matrix metalloproteinases (MMPs) may
      contribute to the pathophysiology of cerebral disease such as ischemic injury. In
      this study, we compared the cellular localization, expression, and activity of
      MMP-2 and -9 in relation to the evolution of neuronal damage 24 and 72 h after
      transient global ischemia. In response to ischemia, there was a generalized
      increase in cellular MMP-2 immunoreactivity at 24-h reperfusion (in neurons, glia
      and vessels) whereas at 72-h reperfusion the increase in MMP-2 was predominantly
      in glia. These glial alterations contributed to a significant increase in pro MMP
      2 levels in ischemic regions (P < 0.01) as measured by zymography. In contrast,
      MMP-9 was predominantly upregulated in neurons and this was significantly
      different to shams at 24- and 72-h reperfusion after ischemia (P < 0.05).
      Notably, a dramatic increase in proteolytic activity in neurons was observed 24 h
      after ischemia and this response was absent at 72 h post-ischemia. The present
      data are supportive of a role for MMPs in contributing to neuronal injury after
      ischemia.

PMID- 15474358
TI  - Polyglutamine repeats of spinocerebellar ataxia 6 impair the cell-death
      preventing effect of CaV2.1 Ca2+ channel--loss-of-function cellular model of
      SCA6.
AB  - Spinocerebellar ataxia (SCA) 6 is caused by small expansion of a polyglutamine
      sequence, encoded by CAG trinucleotide repeats, at the C-terminal end of the
      human CaV2.1 (P/Q-type) Ca2+ channel alpha12.1 subunit and it manifests itself as
      slowly progressive cerebellar ataxia. To elucidate the pathogenic mechanisms
      underlying SCA6, we introduced CAG repeats of various lengths into the Ca2+
      channel alpha12.1 subunit cDNA and expressed them in baby hamster kidney cells
      stably expressing the auxiliary subunits (alpha2delta and beta4). The occurrence
      of cell death differed between cells transfected with the normal and mutant Ca2+
      channels under the condition of serum starvation plus potassium-induced
      depolarization, and Cdk inhibition elucidated the differences more clearly. The
      CaV2.1 (P/Q-type) Ca2+ channel-specific blocker omega-agatoxin IVA abolished the
      cell-death-preventing effect of the normal Ca2+ channel. Together with our
      previous finding that the polyglutamine expansion in SCA6 interferes with the
      Ca2+ channel to reduce Ca2+ influx, these results indicate that impaired function
      of the mutant Ca2+ channels rendered them unable to prevent cell death.

PMID- 15474359
TI  - Mutations in APP have independent effects on Abeta and CTFgamma generation.
AB  - Understanding the molecular mechanism of beta-amyloid (Abeta) generation is
      crucial for Alzheimer's disease pathogenesis as well as for normal APP function.
      The transmembrane domain (TM) of APP appears to undergo presenilin-dependent
      gamma-secretase cleavage at two topologically distinct sites: a site in the
      middle of the TM domain that is crucial for the generation of Abeta-peptides, and
      a site close to the cytoplasmic border (S3-like/epsilon site) of the TM domain
      that leads to production of the APP intracellular domain (CTFgamma/AICD). We
      demonstrate that, in contrast to the unique effect of familial Alzheimer's
      disease (FAD) mutations in APP on Abeta42 production, some but not all FAD
      mutations also affect CTFgamma generation. Furthermore, changes in total CTFgamma
      levels do not correlate with either an increase or a decrease of any Abeta
      species, and inhibition of Abeta-peptide formation starting from position +1
      (Abeta1-x) does not affect CTFgamma production. These results suggest that
      cleavage at the gamma40/42- and the S3-like sites can be dissociated, and that
      APP signaling and Abeta production are not tightly linked.

PMID- 15474360
TI  - Transcriptome analysis in a rat model of L-DOPA-induced dyskinesia.
AB  - We have examined the pattern of striatal messenger RNA expression of over 8000
      genes in a rat model of levodopa (L-DOPA)-induced dyskinesia and Parkinson
      disease (PD). 6-Hydroxydopamine (6-OHDA)-lesioned rats were treated with L-DOPA
      or physiological saline for 22 days and repeatedly tested for antiakinetic
      response to L-DOPA and the development of abnormal involuntary movements (AIMs).
      In a comparison of rats that developed a dyskinetic motor response to rats that
      did not, we found striking differences in gene expression patterns. In rats that
      developed dyskinesia, GABA neurons had an increased transcriptional activity, and
      genes involved in Ca2+ homeostasis, in Ca2+ -dependent signaling, and in
      structural and synaptic plasticity were upregulated. The gene expression patterns
      implied that the dyskinetic striatum had increased transcriptional, as well as
      synaptic activity, and decreased capacity for energy production. Some basic
      maintenance chores such as ribosome protein biosynthesis were downregulated,
      possibly a response to expended ATP levels.

PMID- 15474361
TI  - Shortfalls in the peptidyl-prolyl cis-trans isomerase protein Pin1 in neurons are
      associated with frontotemporal dementias.
AB  - The peptidyl-prolyl cis-trans isomerase (PPIase) Pin1 modulates the activity of a
      range of target proteins involved in the cell cycle, transcription, translation,
      endocytosis, and apoptosis by facilitating dephosphorylation of phosphorylated
      serine or threonine residue preceding a proline (p-Ser/Thr-Pro) motifs catalyzed
      by phosphatases specific for the trans conformations. Pin1 targets include the
      neuronal microtubule-associated protein tau, whose dephosphorylation restores its
      ability to stabilize microtubules. We, and others, have shown that tau
      hyperphosphorylation in the neurofibrillary tangles (NFTs) of Alzheimer disease
      (AD) is associated with redirection of the predominantly nuclear Pin1 to the
      cytoplasm and with Pin1 shortfalls throughout subcellular compartments. As
      nuclear Pin1 depletion causes apoptosis, shortfalls in regard to both nuclear and
      p-tau targets may contribute to neuronal dysfunction. We report here that similar
      Pin1 redistribution and shortfalls occur in frontotemporal dementias (FTDs)
      characterized by abnormal protein aggregates of tau and other cytoskeletal
      proteins. This may be a unifying, contributory factor towards neuronal death in
      these dementias.

PMID- 15474362
TI  - A novel systemically active caspase inhibitor attenuates the toxicities of MPTP,
      malonate, and 3NP in vivo.
AB  - Molecular machinery involved in apoptosis plays a role in neuronal death in
      neurodegenerative disorders such as Parkinson's disease (PD) and Huntington's
      disease (HD). Several caspase inhibitors, such as the well-known peptidyl
      inhibitor carbobenzoxy-Val-Ala-Asp-fluoromethylketone (zVADfmk), can protect
      neurons from apoptotic death caused by mitochondrial toxins. However, the poor
      penetrability of zVADfmk into brain and toxicity limits its use therapeutically.
      In the present study, a novel peptidyl broad-spectrum caspase inhibitor, Q-VD
      OPH, which offers improvements in potency, stability, and toxicity over zVADfmk,
      showed significant protection against 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), 3-nitropropionic acid (3NP), and malonate toxicities.
      Q-VD-OPH significantly reduced dopamine depletion in striatum produced by MPTP
      administration and prevented MPTP-induced loss of dopaminergic neurons in the
      substantia nigra. It significantly reduced the size of striatal lesions produced
      by intrastriatal malonate injections and systemic administration of 3NP. Western
      blots performed on tissues from the midbrain following administration of MPTP or
      the striatum in 3NP-treated animals showed increases of the active forms of
      caspase-9 and caspase-8, as well as the caspase-8-mediated proapoptotic protein
      Bid, which were inhibited Q-VD-OPH treatment. These findings suggest that
      systematically active broad-spectrum caspase inhibitors maybe useful in the
      treatment of neurodegenerative diseases such as PD and HD.

PMID- 15474363
TI  - Coordinated and widespread expression of gamma-secretase in vivo: evidence for
      size and molecular heterogeneity.
AB  - Gamma-secretase is a high molecular weight protein complex composed of four
      subunits, namely, presenilin (PS; 1 or 2), nicastrin, anterior pharynx defective
      1 (Aph-1; A or B), and presenilin enhancer-2 (Pen-2), and is responsible for the
      cleavage of a number of type-1 transmembrane proteins. A fundamental question is
      whether different gamma-secretase complexes exist in vivo. We demonstrate here by
      in situ hybridization and by Northern and Western blotting that the gamma
      secretase components are widely distributed in all tissues investigated. The
      expression of the different subunits seems tightly coregulated. However, some
      variation in the expression of the Aph-1 proteins is observed, Aph-1A being more
      general and abundantly distributed than Aph-1B. The previously uncharacterized
      rodent-specific Aph-1C mRNA is highly expressed in the kidney and testis but not
      in brain or other tissues, indicating some tissue specificity for the Aph-1
      component of the gamma-secretase complex. Blue-native electrophoresis revealed
      size heterogeneity of the mature gamma-secretase complex in various tissues.
      Using co-immunoprecipitations and blue-native electrophoresis at endogenous
      protein levels, we find evidence that several independent gamma-secretase
      complexes can coexist in the same cell type. In conclusion, our results suggest
      that gamma-secretase is a heterogeneous family of protein complexes widely
      expressed in the adult organism.

PMID- 15474364
TI  - Oxygen causes cell death in the developing brain.
AB  - Substantial neurologic morbidity occurs in survivors of premature birth.
      Premature infants are exposed to partial oxygen pressures that are fourfold
      higher compared to intrauterine conditions, even if no supplemental oxygen is
      administered. Here we report that short exposures to nonphysiologic oxygen levels
      can trigger apoptotic neurodegeneration in the brains of infant rodents.
      Vulnerability to oxygen neurotoxicity is confined to the first 2 weeks of life, a
      period characterized by rapid growth, which in humans expands from the sixth
      month of pregnancy to the third year of life. Oxygen caused oxidative stress,
      decreased expression of neurotrophins, and inactivation of survival signaling
      proteins Ras, extracellular signal-regulated kinase (ERK 1/2), and protein kinase
      B (Akt). The synRas-transgenic mice overexpressing constitutively activated Ras
      and phosphorylated kinases ERK1/2 in the brain were protected against oxygen
      neurotoxicity. Our findings reveal a mechanism that could potentially damage the
      developing brain of human premature neonates.

PMID- 15474365
TI  - Lentiviral nigral delivery of GDNF does not prevent neurodegeneration in a
      genetic rat model of Parkinson's disease.
AB  - Viral delivery of glial cell line-derived neurotrophic factor (GDNF) currently
      represents one of the most promising neuroprotective strategies for Parkinson's
      Disease (PD). However, the effect of this neurotrophic factor has never been
      tested in the newly available genetic models of PD based on the viral expression
      of mutated alpha-synuclein. In this study, we evaluated the ability of lentiviral
      vectors coding for GDNF (lenti-GDNF) to prevent nigral dopaminergic degeneration
      associated with the lentiviral mediated expression of the A30P mutant human alpha
      synuclein (lenti-A30P). This virally based rat model develops a progressive and
      selective loss of dopamine neurons associated with the appearance of alpha
      synuclein containing inclusions, thus recapitulating the major hallmarks of PD.
      Lenti-GDNF was injected in the substantia nigra 2 weeks before nigral
      administration of lenti-A30P. Although a robust expression of GDNF was observed
      in the whole nigrostriatal pathway due to retrograde and/or anterograde
      transport, lenti-GDNF did not prevent the alpha-synuclein-induced dopaminergic
      neurodegeneration in the lentiviral-based genetic rat model of PD. These results
      suggest that sustained GDNF treatment cannot modulate the cellular toxicity
      related to abnormal folded protein accumulation as mutated human alpha-synuclein.

PMID- 15474366
TI  - Expression analysis of the N-Myc downstream-regulated gene 1 indicates that
      myelinating Schwann cells are the primary disease target in hereditary motor and
      sensory neuropathy-Lom.
AB  - Mutations in the gene encoding N-myc downstream-regulated gene-1 (NDRG1) lead to
      truncations of the encoded protein and are associated with an autosomal recessive
      demyelinating neuropathy--hereditary motor and sensory neuropathy-Lom. NDRG1
      protein is highly expressed in peripheral nerve and is localized in the cytoplasm
      of myelinating Schwann cells, including the paranodes and Schmidt-Lanterman
      incisures. In contrast, sensory and motor neurons as well as their axons lack
      NDRG1. NDRG1 mRNA levels in developing and injured adult sciatic nerves parallel
      those of myelin-related genes, indicating that the expression of NDRG1 in
      myelinating Schwann cells is regulated by axonal interactions. Oligodendrocytes
      also express NDRG1, and the subtle CNS deficits of affected patients may result
      from a lack of NDRG1 in these cells. Our data predict that the loss of NDRG1
      leads to a Schwann cell autonomous phenotype resulting in demyelination, with
      secondary axonal loss.

PMID- 15474367
TI  - Recessive, but not dominant, mutations in peripheral myelin protein 22 gene show
      unique patterns of aggregation and intracellular trafficking.
AB  - A characteristic feature of mouse models of the peripheral neuropathies caused by
      dominant mutations in peripheral myelin protein 22 (pmp22) is the appearance, in
      Schwann cells, of pmp22 aggregates. Using a set of dominant and recessive pmp22
      mutations that cause human disease of varying degrees of severity, we compared
      their potential for aggregation and trafficking patterns with those of wild-type
      pmp22. The potential for aggregation was assessed by determining the size
      distribution of the various pmp22 mutant proteins under conditions where wild
      type pmp22 showed little or no aggregation. All disease-causing dominant
      mutations showed significant aggregation and failed to traffic to the cell
      surface. Although the position of the dominant mutation in the pmp22 molecule
      determined both its potential for aggregation and how far it trafficked in the
      cell, there was no correlation between aggregation and the severity of the
      disease. On the other hand, recessive mutations were uniquely distinguished from
      dominant mutations by both the low potential for aggregation and their
      trafficking to the cell surface. In the course of these studies, it was also
      noted that the potential for aggregation and the trafficking of mutant pmp22s is
      influenced by the nature and/or location of the epitope tag.

PMID- 15474368
TI  - Neuronal co-expression of EGFP and beta-galactosidase in mice causes
      neuropathology and premature death.
AB  - Dose-dependent co-expression of enhanced green fluorescent protein (EGFP) and
      beta-galactosidase (beta-gal) in the cytoplasm of forebrain neurons of two
      independent mouse lines resulted in growth retardation, weakness, and premature
      lethality. In primary motor cortex and striatum, apoptosis, glial fibrillary
      acidic protein proliferation, and cell loss were found. In addition, we observed
      aggregations of EGFP and beta-gal that colocalized with ubiquitin. GFP is
      unlikely to be toxic per se, as a third mouse line that expressed twice as much
      GFP in the cytoplasm of forebrain neurons as the two affected lines was normal.
      Cytoplasmic aggregations of EGFP and beta-gal occurred in affected and
      phenotypically normal mice suggesting a storage function rather than being
      detrimental. We successfully prolonged survival of affected mice with granulocyte
      colony-stimulating factor (GCSF) and the antibiotic minocycline. These compounds
      could protect neurons from EGFP and beta-gal-induced dysfunction, as demise of
      mice started after treatment was discontinued.

PMID- 15474370
TI  - Activation of the neuronal c-Abl tyrosine kinase by amyloid-beta-peptide and
      reactive oxygen species.
AB  - The deposition and accumulation of amyloid-beta-peptide (Abeta) in the brain are
      considered a sine qua non for Alzheimer's disease. The experimental delivery of
      fibrilized Abeta serves as a cellular model for several facets of the disease
      including the induction of synaptic dysfunction and apoptosis. c-Abl kinase is
      involved in the regulation of apoptosis and its pro-apoptotic function is in part
      mediated by its interaction with p73, a p53 homologue. We found that c-Abl
      activation is involved in cell signals that regulate neuronal death response to
      Abeta fibrils. Abeta peptide fibrils induced an increase of the c-Abl activity in
      rat hippocampal neurons as well as an increase in nuclear p73 protein levels and
      the p73-c-Abl complex. The neuronal cell death induced by Abeta fibrils was
      prevented by the inhibition of c-Abl with imatinib mesylate (Gleevec or STI571)
      and by the inhibition c-Abl expression by RNAi. These results directly point to a
      therapeutic strategy for the treatment of Alzheimer's disease.

PMID- 15474369
TI  - Anti-inflammatory treatment with acetylsalicylate or rofecoxib is not
      neuroprotective in Huntington's disease transgenic mice.
AB  - Inflammatory mechanisms have been implicated in the pathogenesis of Huntington's
      disease (HD). Possible benefits of anti-inflammatory treatments include improved
      folding of mutant huntingtin mediated through chaperones, reduction of
      destructive cellular and humoral inflammatory pathways, and reduction of
      proapoptotic signaling mediated by NF-kappaB or other transcription factors. This
      study was performed to investigate the therapeutic potential of anti-inflammatory
      drugs as treatments for Huntington's disease by examining whether two compounds
      in widespread human use can ameliorate the phenotype of HD transgenic mouse
      models. We examined the effectiveness of acetylsalicylate and rofecoxib as
      treatments for the R6/2 and N171-82Q transgenic mouse models of Huntington's
      disease. Both drugs were administered from weaning. To monitor the effectiveness
      of the treatment, we analyzed the mice for weight loss, behavioral changes, and
      gross cerebral and striatal atrophy. The studies showed that neither drug
      benefited the animals at doses comparable to those tolerated by humans.

PMID- 15474371
TI  - M1 muscarinic receptor activation protects neurons from beta-amyloid toxicity. A
      role for Wnt signaling pathway.
AB  - Amyloid-beta-peptide (Abeta) deposits are one of the hallmark features of
      Alzheimer's disease. Signal transduction alterations are implicate in the
      neuronal responses to Abeta, which include neurotransmitter systems and pathways
      involved in the maintenance of the nervous system. In this context, we have
      recently found that Abeta-neurotoxicity triggers a loss of Wnt signaling. We
      report here that M1-acetylcholine-muscarinic-receptor (mAChR) activation protects
      neurons from Abeta-toxicity. Concomitant with this effect, a modulation of the
      Wnt signaling was observed. M1 mAChR activation inhibits glycogen-synthase-kinase
      3beta (GSK-3beta) activity, stabilizes cytoplasmic and nuclear beta-catenin, and
      induces the expression of the Wnt target genes engrailed and cyclin-D1, reverting
      the switch off of the Wnt pathway caused by Abeta-toxicity. Neurons from mice
      that overexpress GSK-3beta allow us to establish that M1 mAChR stimulation leads
      to GSK-3beta inactivation. We conclude that the cross-talk between the muscarinic
      signaling and Wnt components underlie the neuroprotective effect of the M1 mAChR
      activation.

PMID- 15474372
TI  - Evidence for chronic mitochondrial impairment in the cervical spinal cord of a
      murine model of motor neuron disease.
AB  - Profound alteration of the oxygen consumption rate (QO2) is present in the
      cervical spinal cord (CS) of the wobbler mice aged 12 weeks (wr12). Early
      symptomatic mice at 4 weeks (wr4) show less pronounced changes with decreases of
      basal QO2 (P < 0.03) and of QO2 through complex I (P < 0.04). Mitochondrial
      respiratory enzyme activities, measured spectrophotometrically in the CS
      homogenate, show no difference between wr12 and controls, whereas complex I is
      reduced in the wr4 CS (P < 0.0003). Complex I activity is lower than normal both
      in wr12 and wr4 CS when measured in motor neurons by mean of a histochemical
      technique. Electron microscopy (EM) reveals a mixture of normal and
      morphologically altered mitochondria in wr4 motor neurons. The wobbler lumbar
      spinal cord is spared even at 12 weeks. Our results demonstrate the presence of
      mitochondrial abnormalities in the wobbler CS since the first manifestations of
      the disease. Thus, chronic mitochondrial dysfunction has a contributory role in
      motor neuron degeneration in the wobbler disease.

PMID- 15474373
TI  - Ultraviolet-B signalling: Arabidopsis brassinosteroid mutants are defective in UV
      B regulated defence gene expression.
AB  - The involvement of brassinosteroids in signalling events in plants during UV-B
      stress (280-315 nm) was investigated in Arabidopsis thaliana. Brassinosteroids
      are involved in growth and development in plants and have also been shown to
      enhance stress tolerance. Three mutants deficient in the biosynthetic pathway of
      brassinolide (BL; det2, dim1 and cpd) and the BL insensitive mutant (bri1) were
      together with visible light irradiated with 3 or 9 h of UV-B radiation
      (biologically effective radiation normalised to 300 nm being 0.24 W m(-2)). Also,
      a small size control, irx1, and Columbia 0 (Col-0) wild-type plants were examined
      under identical conditions. Gene expression patterns were established for these
      mutants with a set of four molecular markers (the defence genes chalcone synthase
      (CHS), PYROA, pathogenesis-related protein PR-5, and a gene regulated by very low
      levels of UV-B, MEB5.2). Although the genes in the brassinodefective mutants were
      still induced by UV-B radiation, they all also showed reduced levels of mRNA
      transcripts compared with Col-0 and irx1. The bri1 and cpd were the mutants with
      lowest levels of molecular marker mRNA transcripts. The effects of impairment of
      brassinosteroid signalling also differed between the genes studied, indicating a
      need for a complete brassinosteroid pathway in UV-B signalling.

PMID- 15474374
TI  - Antioxidative responses of Calendula officinalis under salinity conditions.
AB  - To gain a better insight into long-term salt-induced oxidative stress, some
      physiological parameters in marigold (Calendula officinalis L.) under 0, 50 and
      100 mM NaCl were investigated. Salinity affected most of the considered
      parameters. High salinity caused reduction in growth parameters, lipid
      peroxidation and hydrogen peroxide accumulation. Under high salinity stress, a
      decrease in total glutathione and an increase in total ascorbate (AsA + DHA),
      accompanied with enhanced glutathione reductase (GR, EC 1.6.4.2) and ascorbate
      peroxidase (APX, EC 1.11.1.11) activities, were observed in leaves. In addition,
      salinity induced a decrease in superoxide dismutase (SOD, EC 1.15.1.1) and
      peroxidase (POX, EC 1.11.1.7) activities. The decrease in dehydroascorbate
      reductase (DHAR, EC 1.8.5.1) and monodehydroascorbate reductase (MDHAR, EC
      1.6.5.4) activities suggests that other mechanisms play a major role in the
      regeneration of reduced ascorbate. The changes in catalase (CAT, EC 1.11.1.6)
      activities, both in roots and in leaves, may be important in H2O2 homeostasis.

PMID- 15474375
TI  - Carbon dioxide concentrations are very high in developing oilseeds.
AB  - A new method has been developed to rapidly determine the total inorganic carbon
      concentration (gaseous [CO2] + aqueous [CO(2)] + [HCO3-] + [CO3(2)-]) in
      developing seeds. Seeds are rapidly dissected and homogenized in 1 N HCl in gas
      tight vials. The headspace gas is then analyzed by infrared gas analysis.
      Developing rapeseed (Brassica napus L.) and soybean [Glycine max (L.) Merr.]
      seeds were analyzed and found to have up to 40 and 12 mM total inorganic carbon,
      respectively. These concentrations are ca. 600-2000-fold higher than in ambient
      air or values reported for leaves. Carbon dioxide concentrations in rapeseed
      peaked during the stage of maximum oil synthesis and declined as seeds matured.
      The consequences for seed metabolism, physiology and carbon economy are
      discussed.

PMID- 15474376
TI  - Brassinolides and IAA induce the transcription of four alpha-expansin genes
      related to development in Cicer arietinum.
AB  - Four different cDNAs encoding alpha-expansins have been identified in Cicer
      arietinum (Ca-EXPA1, Ca-EXPA2, Ca-EXPA3 and Ca-EXPA4). The shared amino acid
      sequence similarity among the four alpha-expansin proteins ranged from 67 to 89%.
      All of them display common characteristics such as molecular mass (around 24
      kDa), amino acid numbers, and also the presence of a signal peptide. The
      transcription pattern of chickpea alpha-expansin genes in seedlings and plants
      suggests a specific role for each of the four alpha-expansins in different phases
      of development or in different plant organs. High levels of Ca-EXPA2 transcripts
      coincide with maximum epicotyl and stem growth, indicating an important
      involvement of this particular alpha-expansin in elongating tissues. Ca-EXPA3
      would be related to radicle development, while Ca-EXPA4 seems to be involved in
      pod development. A considerable increase in the level of all Ca-EXPA transcripts
      accompanied the indole acetic acid (IAA) plus brassinolide (BR)-induced
      elongation of excised epicotyl segments. This IAA + BR induction was seen even
      for the chickpea expansin genes whose transcription was not affected by IAA or BR
      alone.

PMID- 15474377
TI  - Rhizobial strain involvement in plant growth, nodule protein composition and
      antioxidant enzyme activities of chickpea-rhizobia symbioses: modulation by salt
      stress.
AB  - Mesorhizobium ciceri, Mesorhizobium mediterraneum and Sinorhizobium medicae
      strains showed different symbiotic performances when inoculated to chickpea
      (Cicer arietinum L., cv. chetoui) at unstressed conditions and under salt stress.
      The analysis of nodular proteic composition and antioxidant enzyme activities
      revealed a polymorphism of patterns on SDS and native PAGE suggesting a potential
      dependence on the bacterial partner. Salt effect was analysed on plant growth,
      nitrogen fixation and antioxidant enzymes. M. ciceri, the most efficient strain,
      seemed to allow a best tolerance to chickpea plants under salt stress. This
      constraint did not affect the nodular superoxide dismutase (SOD, E.C. 1.15.1.1)
      activity of the symbiosis implicating the latter strain. This symbiosis showed
      the least decrease for the nodule protein level and the catalase (CAT, E.C.
      1.11.1.6) activity, and the highest increase of peroxidase (POX, E.C. 1.11.1.7)
      activity that seemed to be related with the tolerance to salt.

PMID- 15474378
TI  - Gas chromatography-mass spectrometry analysis of indoleacetic acid and tryptophan
      following aqueous chloroformate derivatisation of Rhizobium exudates.
AB  - A new method for preparing alkyl esters of indole-3-acetic acid (IAA) in aqueous
      solution is adapted from the chloroformate method originally described by Husek
      for the analysis of amino acids. This method has the significant advantage of
      avoiding the generation and use of diazomethane, and is done in aqueous solution
      without the need to dry the sample with concomitant non-specific losses of IAA.
      The effectiveness of this method is demonstrated by its use in an isotope
      dilution gas chromatography-mass spectrometry (GC-MS) assay of IAA and L
      tryptophan (Trp) in the culture supernatant of a series of Sinorhizobium meliloti
      and Rhizobium leguminosarum bv. trifolii strains that can interact with rice to
      either enhance or inhibit rice plant growth. We were testing the hypothesis that
      the rice growth inhibition was related to the biosynthesis of IAA. It was found
      that S. meliloti and Rhizobium strains produced high amounts of IAA in Trp
      supplemented BIII minimal medium compared to BIII media. All the strains produced
      more than the minimum amount of IAA required to inhibit rice growth and thus IAA
      is not the major inhibitory factor of rice seedling growth from S. meliloti and
      Rhizobium strains.

PMID- 15474379
TI  - Over-expression of potato virus X TGBp1 movement protein in transgenic tobacco
      plants causes developmental and metabolic alterations.
AB  - Transgenic Nicotiana tabacum plants expressing the TGBp1 movement protein of
      potato virus X (PVX) were studied to investigate the effects caused by this
      protein on plant physiology and development. TGBp1 caused consistent reductions
      of size and weight in different organs of these plants; however shoot-to-root
      ratios were similar to those of control plants. Transgenic seedlings showed
      smaller root meristems and calli derived from TGBp1 leaves grew at a slower rate
      through successive subcultures. Microscopic observations of TGBp1 plants revealed
      flattened chloroplasts containing plastoglobuli-like bodies. Further analyses
      showed a considerable reduction in photosynthetic rate, lower starch levels in
      leaves and roots, higher nitrate accumulation in leaves and induction of
      pathogenesis-related (PR) protein genes. Since these changes were not observed
      when other PVX sequences were expressed in tobacco, we postulate that TGBp1 is an
      important symptom contributor in PVX infections.

PMID- 15474380
TI  - Differences in the influx of glutamine and nitrate into Viscum album from the
      xylem sap of its hosts.
AB  - The flux of inorganic and organic nitrogen into the mistletoe Viscum album L.
      from the xylem sap of a deciduous (Populus x euamericana) and a coniferous host
      (Abies alba Mill.) was analyzed. For this purpose, a perfusion system was
      developed in which the xylem sap of the host was replaced by an artificial
      perfusion solution. With this system flux rates into the mistletoe were
      determined in feeding experiments either with the organic nitrogen source [1,2
      13C2]glutamine at high and the inorganic nitrogen source 15NO3- at low
      concentration or vice versa. Glutamine influx was already saturated at the low
      concentration in the xylem sap and was--different from nitrate--not enhanced,
      when a 250-fold higher concentration was applied. Nitrate influx matched
      glutamine influx only at high inorganic/organic nitrogen ratios in the perfusion
      solution. This result indicates a preferential influx of glutamine over nitrate
      from the host xylem into the mistletoe at the concentrations found in the xylem
      sap of trees. Surprisingly, a high percentage of both N sources were accumulated
      in the mistletoe stem, indicating excessive N nutrition of the mistletoe leaves.
      Since 13C isotope signature was significantly reduced in the outflowing perfusion
      solution, either an upload of organic compounds from the phloem into the xylem,
      or an efflux of organic compounds from haustorium of mistletoe into the xylem has
      to be assumed. 15N isotope signatures enriched in the outflowing perfusion
      solution support the idea of a nitrate uptake system at the host xylem-haustorium
      interface, which favors the light N isotope of nitrate.

PMID- 15474381
TI  - Co-expression of an ethylene receptor gene, ERS1, and ethylene signaling
      regulator gene, CTR1, in Delphinium during abscission of florets.
AB  - We are trying to determine the mechanisms responsible for ethylene-induced floret
      abscission in cut flowers of Delphinium and recently identified an ethylene
      receptor gene, ERS1, and studied its response to ethylene treatment. In order to
      identify additional components of the ethylene response network in Delphinium, we
      performed 3' and 5' rapid amplification of cDNA ends (RACE) using the consensus
      sequence of the serine/threonine kinase domain of the ethylene signaling
      regulator gene (CTR1) involved in the constitutive triple response (CTR) to
      ethylene. The full-length cDNA (2754 nt) encoded a protein of 800 amino acids,
      which contained the expected serine/threonine kinase domain, the consensus ATP
      binding site, and the serine/threonine kinase catalytic site. The protein had
      quite high (>50%) overall identity to CTR1 from Arabidopsis and tomato, and 70
      75% identity in the catalytic site. The amount of mRNA encoding both CTR1 and
      ERS1 more than doubled within 6 h in cut florets incubated in the presence of
      exogenous ethylene. Similarly, the amount of ERS1 transcript doubled in florets
      within 6 d of harvesting, presumably in response to endogenous ethylene, while
      CTR1 mRNA increased to about 40% over the same period. However, in the presence
      of silver thiosulfate (STS), an ethylene inhibitor, the level of both transcripts
      remained essentially unchanged for the first 8 d before declining to very low
      levels. Florets on the control plants had almost completely abscised by 6 d, but
      the florets on STS-treated plants had not abscised by 20 d, by which time the
      flowers were almost dead. The data are consistent with the hypothesis that
      endogenous ethylene evokes the accumulation of both these transcripts (and their
      encoded proteins), thereby speeding up abscission and reducing the useful shelf
      life of the cut flowers.

PMID- 15474382
TI  - The B cell: a new therapeutic target in rheumatoid arthritis and other autoimmune
      diseases.

PMID- 15474383
TI  - Benefits, limitations, and impact of osteoporosis risk factor identification.

PMID- 15474384
TI  - Combination therapy for osteoporosis.

PMID- 15474385
TI  - The ANKH gene and familial calcium pyrophosphate dihydrate deposition disease.
AB  - Familial calcium pyrophosphate dihydrate deposition (CPPD) disease is a chronic
      condition in which CPPD microcrystals deposit in the joint fluid, cartilage, and
      periarticular tissues. Two forms of familial CPPD disease have been identified:
      CCAL1 and CCAL2. The CCAL1 locus is located on the long arm of chromosome 8 and
      is associated with CPPD and severe osteoarthritis. The CCAL2 locus has been
      mapped to the short arm of chromosome 5 and identified in families from the
      Alsace region of France and the United Kingdom. The ANKH protein is involved in
      pyrophosphate metabolism and, more specifically, in pyrophosphate transport from
      the intracellular to the extracellular compartment. Numerous ANKH gene mutations
      cause familial CCAL2; they enhance ANKH protein activity, thereby elevating
      extracellular pyrophosphate levels and promoting the formation of pyrophosphate
      crystals, which produce the manifestations of the disease. Recent studies show
      that growth factors and cytokines can modify the expression of the normal ANKH
      protein. These results suggest a role for ANKH in sporadic CPPD disease and in
      CPPD associated with degenerative disease.

PMID- 15474386
TI  - Treatment of lateral epicondylitis: where is the evidence?
AB  - Lateral epicondylitis is the most commonly diagnosed elbow condition and affects
      about 1-3% of the population at large. It produces a heavy burden of workdays
      lost and residual impairments. Although many treatment modalities are used, few
      of them rest on scientific evidence and none has been proven more effective than
      the others. This paucity of evidence on treatments for lateral epicondylitis may
      stem from several sources, including the possible self-limiting nature of the
      condition, the lack of pathophysiological data, the methodological shortcomings
      of available studies, and the existence of numerous factors influencing the
      outcome.

PMID- 15474387
TI  - Role for suppressor T cells in the pathogenesis of autoimmune diseases (including
      rheumatoid arthritis). Facts and hypotheses.
AB  - Although uncontrolled clones of autoreactive T cells play a central role in the
      pathogenesis of autoimmunity, another mechanism potentially involved in many
      autoimmune diseases is deficiency of suppressor T cells, most notably those
      belonging to the antiidiopeptide TH3/Tr1 TCD4+CD25+(high) subset. Failure of
      suppressor mechanisms may be in part primary, due to defective positive selection
      of suppressor T cells in the thymus, and in part acquired, secondary to chronic
      infections promoted by deficiencies in innate immunity. Renewed interest in
      suppressor TCD4+ cells has generated plausible explanations for many events
      including paradoxical induction of autoimmune disorders by immunosuppressive
      agents or thymectomy. Insights into the physiology of these regulatory T-cell
      clones might suggest new treatment options, although many currently used drugs
      (including anti-TNF alpha agents) enhance the activity of several suppressor T
      cell clones. Investigation of these suppressor clones in rheumatoid arthritis is
      still in its infancy and faces obstacles such as the need for identifying key
      clones in each individual patient and the presence of T-cell repertoire
      contraction. This last phenomenon exists at disease onset and may stem from early
      thymus dysfunction, which may also lead to a reduction in suppressor TCD4+ cell
      counts. Thus, although restoring deficient suppressor clones may provide a full
      recovery in animals, the high prevalence of T-cell repertoire contraction in
      humans with rheumatoid arthritis may severely limit the beneficial effects of
      this therapeutic approach.

PMID- 15474388
TI  - Fabry disease: a review.
AB  - Fabry disease is an inherited deficiency of the lysosomal hydrolase alpha
      galactosidase A (alpha GalA) due to mutations in the Gal gene at Xq22. The result
      is intralysosomal accumulation of glycosphingolipids. In males who carry the
      mutation (1/40,000), severe multisystem disease develops in childhood or
      adolescence. Attacks of acute pain lasting a few minutes to a few days occur in
      the hands and feet, joints, muscles, and abdomen, sometimes with a fever. Highly
      suggestive skin lesions called angiokeratomas develop, as well as cornea
      verticillata characterized by corneal deposits without visual impairment. Stroke,
      seizures, heart disorders (conduction disturbances, valve disease, and left heart
      failure) and kidney disorders (proteinuria and chronic renal failure) develop in
      the third or fourth decade of life. Women who are heterozygous for the Gal gene
      can transmit the disease to their sons but are usually free of symptoms, although
      many have cornea verticillata. However, they may have moderate or severe disease
      related to uneven chromosome X inactivation. Late-onset variants with predominant
      neurological, cardiac, or renal manifestations have been described. The diagnosis
      is difficult when the family history is negative for Fabry disease. Tests on
      plasma and leukocytes show very low levels of alpha GalA activity in affected
      men, confirming the diagnosis. The Gal gene mutation should be looked for to
      detect heterozygous women. Symptomatic treatments include analgesics,
      antihypertensives, antiplatelet agents or anticoagulants to treat ischemic
      events, and hemodialysis or kidney transplantation to treat chronic renal
      failure. The recent introduction of enzyme replacement therapy with recombinant
      agalsidase alpha or beta has been a major breakthrough in the treatment of Fabry
      disease. Enzyme replacement therapy relieves the pain and decreases the risk of
      complications. The safety profile is good. Given the high cost of agalsidase
      therapy (about 160,000 euro/year/patient) and the low incidence of Fabry disease,
      patients should be referred to highly specialized centers (see addresses on the
      France Orphanet web site).

PMID- 15474389
TI  - Evaluation of metacarpophalangeal joint synovitis in rheumatoid arthritis by
      power Doppler technique: relationship between synovial vascularization and
      periarticular bone mineral density.
AB  - OBJECTIVE: To evaluate intra-articular vascularization and flow patterns of the
      metacarpophalangeal (MCP) joints in rheumatoid arthritis (RA) patients by using
      power Doppler technique. The relationship between the flow patterns and the
      regional bone mineral density (BMD) measurements of MCP joints using dual-energy
      X-ray absorptiometry (DXA) was also assessed. METHODS: Fifteen patients (mean age
      48.5 +/- 13.8) with a disease duration of 6.8 +/- 4.9 years were included into
      the study. Thirty MCP joints of three healthy subjects were also assessed as
      controls. Clinical activity of MCP joint inflammation was classified according to
      a modified index for synovitis activity based on joint swelling, warmness and
      pain. Ultrasonography was performed using LOGIQ 7 unit by means of a 6-13 MHz
      linear array transducer. Gray-scale US and power Doppler sonography (PDS)
      examination was performed. Using spectral Doppler the quality of flow was
      determined and the indices of pulsatility (PI) and resistance (RI) were measured
      in longitudinal plane. The erosive scores of the MCP joints were determined on
      the plain hand radiographs using Sharp/van der Heijde method. Hand BMD, MCP BMD
      and the ratio of MCP BMD to whole hand BMD (rBMD) were measured using a Lunar DPX
      densitometer. RESULTS: Total 150 MCP joints of 15 patients and 30 MCP joints of
      three healthy controls were examined in both hands. Flow was determined in 31
      joints (10 moderately active, 21 active) in eight patients whereas seven patients
      had no quantifiable flow in MCP joints. MCP joints of healthy controls had no
      quantifiable flow. Mean PI of these joints were 2.17 +/- 2.37 in moderately
      active and 2.12 +/- 1.93 in active MCP joints. RI was 0.76 +/- 0.12 in moderately
      active and 0.75 +/- 0.15 in active MCP joints. There was no significant
      difference in RI and PI of these active and moderately active MCP joints. There
      was a significant correlation between erosive scores and PI, RI of total MCP
      joints (r = 0.40 and r = 0.41, P < 0.05). PI and RI also negatively correlated
      with rBMD (r = -0.46, P < 0.01 and r = -0.36, P < 0.05, respectively). PIc was
      4.07 +/- 3.26 and RIc was 0.88 +/- 0.16 in the neighboring soft tissues which
      were significantly higher than PI and RI of MCP joints (P < 0.001). CONCLUSION:
      Power Doppler ultrasonography (PDUS) is a useful method demonstrating synovial
      vascularization and flow patterns and offers new alternatives for monitoring
      disease activity and measurement of therapeutic response. Flow patterns had
      intimate correlation with intra-articular bone and cartilage destruction.

PMID- 15474390
TI  - Assessing damage in individual joints in rheumatoid arthritis: a new method based
      on the Larsen system.
AB  - OBJECTIVES: To evaluate observer agreement using the Larsen system (LS) and a
      Modified Larsen system (ML) when assessing individual joints of the hands and
      wrists in rheumatoid arthritis, and to compare the two systems. To determine the
      minimally important difference (MID) for the ML. METHODS: Thirty radiographs of
      hands and wrists from 10 patients who presented with RA were graded by two
      blinded observers, using the LS and then the ML. Patients were followed for a
      mean of 7.2 years (range: 4-10 years). Inter- and intra-observer agreement were
      calculated using the kappa statistic with linear incremental weights. Inter
      observer agreement was also computed for the summed score, using an intraclass
      correlation coefficient. Inter-observer error was estimated by calculating the
      mean and standard deviation of the grading differences between the two observers.
      Prevalence of damage was calculated as a ratio of damage: no damage and expressed
      as a percentage. Pairs of radiographs were comparatively graded using a seven
      point Likert scale. RESULTS: The kappa statistic for inter-observer agreement was
      0.38 (marginal reproducibility) for the LS and 0.52 (good reproducibility) for
      the ML (P = 0.004). Using a difference of one grade as perfect agreement, it was
      0.56 (good reproducibility) for the LS and 0.87 (excellent reproducibility) for
      the ML (P = 0.001). Intra-observer agreement was high in both systems. The
      distribution of ML-grade differences varied according to the level of the Likert
      scale: for "a little bit worse", representing the smallest amount of detectable
      damage progression, the distribution differences peaked around two grades. This
      value represented a MID 87% of the time. CONCLUSIONS: The LS lacks precision for
      individual joints. The ML, it is proposed, has more detailed definitions of
      grades, and is more reliable. When pairs of radiographs were compared, a two
      grade difference on the ML was the MID.

PMID- 15474391
TI  - Is the incidence of elbow osteoarthritis underestimated? Insights from
      paleopathology.
AB  - OBJECTIVES: Osteoarthritis is uncommon at the elbow in contemporary populations.
      We sought to determine whether this was also the case in medieval and premodern
      times. MATERIAL AND METHODS: Standard criteria for osteoarthritis were applied to
      496 complete elbows from a necropolis in Provence, France. RESULTS:
      Osteoarthritis was found in 27% of elbows. Significant differences were noted
      across periods and age groups but not between the right and left sides.
      CONCLUSION: Our data suggest that the symptoms of elbow osteoarthritis may be far
      milder than expected from the underlying pathological lesions. The incidence of
      elbow osteoarthritis in contemporary populations is probably underestimated. The
      high prevalence of elbow osteoarthritis in archeological populations cannot be
      taken as a marker for activities placing stress on the upper limbs.

PMID- 15474392
TI  - Familial calcium pyrophosphate dihydrate deposition disease. A Tunisian kindred.
AB  - INTRODUCTION: Familial calcium pyrophosphate dihydrate deposition disease (CPDD)
      is uncommon, with about 50 affected families identified to date in the world.
      Genetic studies in familial CPDD are focusing on the ANKH gene. We report a new
      Tunisian kindred with CPDD. PATIENTS AND METHODS: The development of CPDD in a
      patient who was only 35 years of age prompted a family study. A medical history,
      physical examination, and radiographs were performed in 103 family members older
      than 18 years. RESULTS: Fifteen family members had CPDD. There were 10 men and
      five women, with a mean age of 59.4 years. Onset was usually in the third or
      fourth decade. Four clinical patterns were found: Five patients had pseudogout,
      five had pseudoosteoarthritis, three had asymptomatic disease, and two had
      pseudorheumatoid arthritis. Inheritance was autosomal dominant with low
      penetrance. No associations with specific HLA antigens were found. The disease
      was mild. These characteristics fit the description of Gaucher type 1 familial
      CPDD. CONCLUSION: Inherited autosomal dominant CPDD with low penetrance was found
      in 15 members of a Tunisian kindred. The disease was mild. We are planning a
      genetic study including tests for ANKH gene mutations in this kindred.

PMID- 15474393
TI  - Estimated number of women likely to benefit from bone mineral density measurement
      in France.
AB  - OBJECTIVES: To determine the number of women in France at least 50 years of age
      with risk factors for osteoporosis likely to lead to bone mineral density
      measurement, an investigation reimbursed by the French national health insurance
      system in patients at risk for osteoporosis. The study was commissioned by the
      French health authorities. MATERIALS AND METHODS: Risk factors for osteoporosis
      were defined as recommended by the French Agency for Accreditation and Evaluation
      in Health (ANAES) in 2001. The study data were from nine cohort studies done in
      France and from the National Health Insurance Agency for the Rhone-Alpes region
      of France. Risk factor prevalences in France were standardized by extrapolation
      according to the age distribution in France. RESULTS: Overall, data were
      collected in 123,986 women aged 50 years or older. From these data, risk factor
      estimates were as follows: menopause before 40 years of age, 1.5 million women;
      body mass index (BMI) lower than 19 kg/m(2), nearly 700,000; history of fracture,
      more than 2 million; history of femoral neck fracture in the mother, more than 1
      million; history of health problems potentially responsible for osteoporosis,
      400,000; and history of long-term glucocorticoid therapy, 612,000. In all,
      3,186,318 (30%) women were estimated to have at least one risk factor and 785,512
      (7.5%) at least two risk factors. CONCLUSIONS: Although our study sample was not
      representative of the population residing in France, the large sample size and
      diversity of data sources support the validity of our estimate of the prevalence
      of risk factors for osteoporosis in postmenopausal women living in France.

PMID- 15474394
TI  - Discrimination of osteoporotic patients with quantitative ultrasound using
      imaging or non-imaging device.
AB  - OBJECTIVES: Quantitative ultrasound (QUS) has emerged as a new tool in the
      assessment of fracture risk. The aim of this study was to compare the clinical
      utility of QUS parameters measured using imaging and non-imaging devices in the
      discrimination of osteoporotic patients. METHODS: QUS (Broadband Ultrasound
      Attenuation, BUA dB/MHz, and Speed of Sound, SOS m/s) were measured and then
      statistical analyses were performed. RESULTS: The 106 women included were 65 +/-
      8 years aged. Using DXA, T score was < or = -2.5 at either lumbar spine or hip in
      59% of patients, and 25% had osteoporotic fractures. QUS results were different
      among devices, and these differences were highly dependent on the measured value.
      There was a similar effect of age and duration of menopause for all parameters.
      To obtain 90% of sensitivity for the diagnosis of osteoporosis, the thresholds
      were 50.80 and 71.70 dB/MHz for BUA and 1544.80 and 1551.50 m/s for SOS, using
      imaging and non-imaging devices, respectively. Belonging to the highest tertile
      of QUS had a negative predictive value for osteoporosis ranging from 59% to 65%.
      In the lowest tertile of QUS, the proportion of osteoporotic women was between
      73% and 80%. All QUS parameters, except BUA measured with the non-imaging device,
      were able to discriminate post-menopausal women with fractures after adjustment
      for age and hip BMD. CONCLUSIONS: Our data suggest that an imaging system
      improves the utility of BUA measurement, but not SOS, for post-menopausal
      osteoporosis assessment.

PMID- 15474395
TI  - RS3PE revealing recurrent non-Hodgkin's lymphoma.
AB  - A patient meeting published criteria for remitting seronegative symmetrical
      synovitis with pitting edema (RS3PE) was found to have a synchronous recurrence
      of non-Hodgkin's malignant lymphoma. Reported cases of RS3PE associated with
      hematological malignancies and other forms of cancer are reviewed.

PMID- 15474396
TI  - Excision arthroplasty of superior tibiofibular joint for recurrent proximal
      tibiofibular cyst. A report of two cases.
AB  - Synovial cysts originating from proximal tibiofibular joint are commonly
      symptomatic. They can progress to cause pressure effects over the common peroneal
      nerve. In order to prevent recurrence the importance of excision of the ganglion
      and its stalk is emphasised. In recurrent cases treatment can be difficult. We
      describe an operation where after recurrence superior tibiofibular joint excision
      along with the cyst led to complete recovery in two cases.

PMID- 15474397
TI  - A novel finding in thoracic outlet syndrome: tachycardia.
AB  - In this case report, we rendered a 22 year old woman with the diagnosis of
      neurogenic thoracic outlet syndrome. We have evaluated her symptoms of
      palpitation with Holter monitorization during Roos test before and after surgery
      where transaxillary first rib resection and scalenectomy were performed.
      Postoperatively she improved and the tachycardia resolved. We propose that
      stellate ganglion or postganglionic efferent sympathetic fibers forming the
      cardiac plexus are exposed to compression while Roos test is being performed. Due
      to this irritation, there can be an increase in the cardiac sympathetic activity.

PMID- 15474398
TI  - Sciatica, disk herniation, and neuroborreliosis. A report of four cases.
AB  - We report four cases of sciatica in patients with same-level disk herniation
      confirmed by computed tomography and a final diagnosis of acute radiculitis
      caused by Borrelia burgdorferi, with a favorable response to ceftriaxone therapy.
      The neurological manifestations of Lyme disease are protean, and a potential
      contribution of concomitant disk disease to sciatica can lead to diagnostic
      wanderings. Disk lesions and infectious conditions that can cause sciatica are
      discussed. Whether a favorable response to antibiotic therapy should be taken as
      proof of B. burgdorferi radiculitis deserves discussion. In practice, in a
      patient with clinical manifestations suggesting disk-related nerve root pain and
      residing or having traveled to an endemic area, B. burgdorferi infection should
      be looked for, as both etiologies can coexist.

PMID- 15474399
TI  - Granulomatous synovitis after intraarticular Hylan GF-20. A report of two cases.
AB  - Intraarticular hyaluronan injections are used to treat osteoarthritis of the
      knee. Acute painful swelling with a joint effusion develops locally after the
      injection in about 10% of cases but resolves spontaneously. Crystals are
      identifiable in some patients, but the mechanism in crystal-negative cases
      remains unknown. We report knee arthritis with inflammatory joint fluid free of
      organisms and crystals in two patients after Hylan GF-20 treatment for
      femorotibial osteoarthritis. Synovial membrane histology disclosed granulomatous
      synovitis with epithelioid histiocytic and multinucleate giant cells but no
      visible foreign bodies. These two cases suggest that crystal-negative arthritis
      after Hylan GF-20 injection may be ascribable to granulomatous synovitis of the
      foreign-body giant-cell type.

PMID- 15474400
TI  - Coexistent polyarthritis in a married couple.

PMID- 15474401
TI  - Systemic lupus erythematosus developing in a patient with pulmonary sarcoidosis.

PMID- 15474402
TI  - Cutaneous vasculitis and glomerulonephritis in a patient taking the anti-TNF
      alpha agent etanercept for rheumatoid arthritis.

PMID- 15474404
TI  - Reflex sympathetic dystrophy of the foot: MRI with fat suppression is essential
      (letter with the drafting).

PMID- 15474405
TI  - The potent colon carcinogen, 1,2-dimethylhydrazine induces mutations primarily in
      the colon.
AB  - 1,2-Dimethylhydrazine (DMH) is a potent colon carcinogen that is commonly used as
      an initiator in studies of the effects of diet on colon cancer. Previous studies
      have shown that although this compound produces multiple tumors in the colons in
      most individuals of every species tested, it is, at best, marginally mutagenic in
      the bone marrow (micronuclei) and small intestine (Dlb-1 mutations). Here we
      report its mutagenicity in the primary target tissue, the colonic epithelium, by
      means of the Mutatrade markMouse cII assay, an assay for intragenic mutations in
      a lambda shuttle vector that is integrated into the genome of these mice. Animals
      were treated with 0, 10, 20, or 30 mg/ml of DMH, either as a single injection or
      as multiple weekly injections, and mutations were measured in both the small
      intestine and colon. In the small intestine, there was an increase in mutant
      frequency following a single injection of DMH, but this was significant only at
      30 mg/kg [induced mutant frequency (MF) = 18 x 10(-5) mutants/plaque]. In the
      colon, following a single treatment of DMH, there was a significant increase in
      mutant frequency at doses of 20 and 30 mg/kg (induced MF = 17 x 10(-5) and 23 x
      10(-5) mutants/plaque, respectively). Following ten injections of 20 mg/kg of
      DMH, there was a greater than ten-fold increase in mutations in the colon (MF =
      275 x 10(-5) mutants/plaque) than the small intestine (MF = 25 x 10(-5)
      mutants/plaque). These results show that DMH, under the conditions typically used
      for dietary studies, induces large numbers of mutations in the tissue in which it
      induces most cancers.

PMID- 15474406
TI  - Detection by 32P-postlabelling of 8-oxo-7,8-dihydro-2'-deoxyguanosine in DNA as
      biomarker of microcystin-LR- and nodularin-induced DNA damage in vitro in primary
      cultured rat hepatocytes and in vivo in rat liver.
AB  - Microcystin-LR (MCYST-LR) and nodularin (NOD) produced by cyanobacteria are
      potent and specific hepatotoxins. The induction of free-radical formation,
      reduction of glutathione levels and induction of DNA damage are three major
      events found in rat hepatocytes treated with these hepatotoxins. However, the
      mechanism of MCYST-LR- and NOD-mediated induction of oxidative DNA damage has not
      been fully elucidated. The objective of this study was to determine whether MCYST
      LR and NOD increase the formation of a DNA oxidative damage marker such as 8-oxo
      7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in vitro in primary rat hepatocytes and
      in vivo in rat liver cells. Rat hepatocytes were exposed to MCYST-LR or NOD at
      low doses (2 and 10 ng/ml), at which there is no evidence of morphologically
      apparent cytotoxic effects, as well as an induced dose- and time-dependent
      formation of 8-oxo-dG. Moreover, MCYST-LR treatment of rats (50 microg/kg, ip)
      resulted in a significant increase of 8-oxo-dG in liver DNA, at 24 h after
      treatment before decreasing at 48 h. However, NOD-induced DNA damage was
      increased both at 24 and 48 h, in contrast to the MCYST-LR-induced effect. The
      effects on this oxidative DNA damage marker indicates that MCYST-LR and NOD do
      evoke oxidative stress, which may contribute, at least in part, to their liver
      toxicity and carcinogenicity during long-term exposure.

PMID- 15474407
TI  - DNA fragmentation, DNA repair and apoptosis induced in primary rat hepatocytes by
      dienogest, dydrogesterone and 1,4,6-androstatriene-17beta-ol-3-one acetate.
AB  - Four steroids that share the 17-hydroxy-3-oxopregna-4,6-diene structure -
      cyproterone acetate, chlormadinone acetate, megestrol acetate, and potassium
      canrenoate - have been shown previously to behave with different potency as liver
      specific genotoxic agents, the response being markedly higher in female than in
      male rats, but similar in humans of both genders. In this study, performed to
      better define the relationship between chemical structure and genotoxicity,
      dydrogesterone (DGT) with double bonds C4=C5 and C6=C7, dienogest (DNG) with
      double bonds C4=C5 and C9=C10, and 1,4,6-androstatriene-17beta-ol-3-one acetate
      (ADT) with double bonds C1=C2, C4=C5 and C6=C7, were compared with cyproterone
      acetate (CPA) for their ability to induce DNA fragmentation and DNA repair
      synthesis in primary cultures of hepatocytes from three rats of each sex. At
      subtoxic concentrations, ranging from 10 to 90 microM, all four steroids
      consistently induced a dose-dependent increase of DNA fragmentation, which in all
      cases was higher in females than in males; their DNA damaging potency decreased
      in the order CPA > DNG > ADT > DGT. Under the same experimental conditions, the
      responses provided by the DNA repair-synthesis assay were positive or
      inconclusive in hepatocytes from female rats and consistently negative in
      hepatocytes from male rats. In the induction of apoptotic cells, examined in
      primary hepatocytes from female rats, CPA was more active than ADT and DGT, and
      DNG was inactive. Considered as a whole these findings suggest that a liver
      specific genotoxic effect more marked in female than in male rats might be a
      common property of steroids with two or three double bonds.

PMID- 15474408
TI  - Comparative study of the antimutagenic potential of Vitamin E in different E.
      coli strains.
AB  - The antimutagenic potential of Vitamin E due to its antioxidative properties was
      studied. The new Escherichia coli K12 assay-system designed in our laboratory was
      employed in order to detect the antimutagenic potential of Vitamin E and to
      determine its molecular mechanisms of action. The assay is composed of three
      tests. In Test A, we examine the influence of the antioxidant on induced
      oxidative mutagenesis in a repair-proficient strain. Spontaneous mutagenesis is
      monitored in Test B, which is performed with two mutator strains, one mismatch
      repair-deficient (mutS) and another deficient in 8-oxo-dGTP-ase activity (mutT).
      In Test M, a repair-proficient strain and its mismatch repair-deficient
      counterpart (mutH), both carrying a plasmid with microsatellite sequences, are
      used to measure the level of microsatellite instability. To examine the
      antimutagenic potential of Vitamin E we also used the WP2 antimutagenicity test.
      Protective properties of Vitamin E against oxidative mutagenesis were detected in
      all tests with the E. coli K12 assay-system as well as in the WP2
      antimutagenicity test. This study confirms that mismatch repair is essential for
      repair of oxidative DNA damage. The results obtained indicate that Vitamin E
      prevents the formation of DNA adducts by lipid peroxidation products rather than
      those formed by direct oxidation of DNA bases. Moreover, it can reduce
      microsatellite instability. After further validation, the new E. coli K12 assay
      system can be used to test the antimutagenic potential of antioxidants.

PMID- 15474409
TI  - Di-epoxides of the three isomeric dicyclopenta-fused pyrenes: ultimate mutagenic
      active agents.
AB  - To rationalize the high bacterial mutagenic response recently found for the (di-)
      cyclopenta-fused pyrene congeners, viz. cyclopenta[cd]-(1), dicyclopenta[cd,mn]
      (2), dicyclopenta[cd,fg]-(3) and dicyclopenta[cd,jk]pyrene (4), in the presence
      of a metabolic activation mixture (S9-mix), their (di-)epoxides at the externally
      fused unsaturated five-membered rings were previously proposed as the ultimate
      mutagenic active forms. In this study, cyclopenta[cd]pyrene-3,4-epoxide (5) and
      the novel dicyclopenta[cd,mn]pyrene-1,2,4,5-di-epoxide (6),
      dicyclopenta[cd,fg]pyrene-5,6,7,8-di-epoxide (7) and dicyclopenta[cd,jk]pyrene
      1,2,6,7-di-epoxide (8) were synthesised from 1 to 4, respectively, and
      subsequently assayed for bacterial mutagenicity in the standard
      microsomal/histidine reverse mutation assay (Ames-assay with Salmonella
      typhimurium strain TA98). The di-epoxides 6-8 are present as a mixture of their
      cis- and trans-stereo-isomers in a close to 1:1 ratio ((1)H NMR spectroscopy and
      ab initio IGLO/III//RHF/6-31G** calculations). The direct-acting mutagenic
      activity and the strong cytotoxicity exerted by 5-8 both in the absence or
      presence of an exogenous metabolic activation system (+/-S9-mix) demonstrate that
      the ultimate mutagenic active forms are the proposed (di-)epoxides of 1-4.

PMID- 15474410
TI  - Genotoxicity studies on the antimicrobial drug sulfamethoxazole in cultured human
      lymphocytes.
AB  - The genotoxicity of the antimicrobial drug sulfamethoxazole was evaluated in
      cultured human peripheral blood lymphocytes. The frequencies of sister-chromatid
      exchange (SCE) and micronuclei (MN) were scored as genetic endpoints. Both tests
      cover a wide range of induced genetic damage such as primary DNA damage,
      clastogenicity and aneugenicity. Cultures were set up with blood samples from two
      healthy donors and the treatment was done with different sulfamethoxazole
      concentrations ranging from 10 to 500 microg/ml. From the results obtained it
      appears that this drug is able to induce weak genotoxic effects, as revealed by
      the slight increase in the SCE and MN frequencies, at least at one of the two
      highest concentrations tested. However, the results of the SCE assay should be
      interpreted with caution because the increase is just significant. In addition,
      cyotoxic/cytostatic effects of sulfamethoxazole were revealed by a decrease in
      the proliferative rate index (PRI) and in the cytokinesis block proliferation
      index (CBPI).

PMID- 15474411
TI  - DNA breaks as measured by the alkaline comet assay in exfoliated cells as
      compared to voided urine cytology in the diagnosis of bladder cancer: a study of
      105 subjects.
AB  - In this study we evaluated the clinical usefulness of identifying urothelial
      cells with increased DNA damage with the alkaline comet assay and compare it with
      voided urine cytology for the assessment of markers indicative of bladder cancer.
      The analysis was carried out on 105 subjects having clinical suspicion of bladder
      cancer, and who had undergone cytology for the first time. Urine cytology and
      alkaline comet assay were performed on the same fresh urine samples obtained from
      each patient. The subjects were divided according to negative or positive
      cytology. The Mann-Whitney U-test showed that the comet parameters (tail moment,
      tail length, and % of DNA in the tail) and the numbers of comets (cells with an
      arbitrary cut-off value of head intensity <90% of DNA content) in subjects
      positive in both tests were significantly higher than in the negative group.
      Sensitivity, specificity, and positive and negative predictive value of the comet
      assay were compared with those of cytology, which is regarded as the gold
      standard. Sensitivity was 71.4%, specificity was 91.8%, positive and negative
      predictive values were 38.5 and 97.8, respectively. Two subjects negative in the
      comet assay were positive in cytology. Eight patients were positive in the comet
      assay and negative for cytology. Interestingly, one of these eight patients was
      later found positive for cytology. Logistic regression analysis indicates that
      the tail moment is significantly associated with an increased risk for positive
      cytology.

PMID- 15474412
TI  - Evaluation of micronucleus induction in a Chilean population environmentally
      exposed to arsenic.
AB  - In the present study we have evaluated whether or not environmental exposure to
      arsenic in ground drinking-water results in a significant increase in the
      frequency of micronuclei (MN) in peripheral blood lymphocytes. Thus, 106
      individuals from the Antofagasta region (North Chile), together with 111
      individuals from the area of Concepcion, were used in this investigation. In the
      Antofagasta area, arsenic levels in drinking-water as high as 0.750 mg/L were
      measured. In Concepcion, located about 2500 km towards the south and used as
      reference area, arsenic levels in tap water were as low as 0.002 mg/L. The total
      content of arsenic in fingernails was determined as a biomarker of individual
      exposure. The cytogenetic results obtained in this study indicate that in the
      exposed group the overall frequency of binucleated micronucleated cells (BNMN) is
      higher than in the reference group, the difference being statistically
      significant. In addition, no differences were found between the exposed and the
      reference groups, regarding the cytokinesis-block proliferation index (CBPI). No
      association was observed between BNMN and arsenic content in water or arsenic in
      fingernails. On the other hand, when the exposed group was divided according to
      their Atacameno or Caucasian ethnicity, no significant differences were observed
      between them. In addition, as usually found in other human biomonitoring studies,
      sex and age are factors that modulate the frequency of MN in both exposed and
      reference populations.

PMID- 15474413
TI  - Use of whole blood directly for single-cell gel electrophoresis (comet) assay in
      vivo and white blood cells for in vitro assay.
AB  - The present study investigated the use of whole blood from humans and rats
      directly for single-cell gel electrophoresis (comet) assay. As little as 20
      microl of whole blood was sufficient for comet assay, and the comet images
      obtained from whole blood were not different from those obtained from isolated
      lymphocytes. The DNA remained intact up to 4 h at 4 degrees C after isolation and
      had no observable strand breakage, when whole blood was cryopreserved (at -80
      degrees C) in 10% pre-cooled DMSO up to 60 days. To demonstrate that the whole
      blood technique could be applied to in vivo studies, we injected rats with a
      known carcinogen Fe/NTA and measured DNA strand breaks in whole blood in
      comparison with isolated lymphocytes. We showed that Fe/NTA injection resulted in
      similar extent of DNA strand breakage in both whole blood and lymphocytes,
      indicating that whole-blood method can be used for in vivo genotoxic studies. One
      disadvantage of the whole-blood technique is that whole blood cannot be used for
      in vitro studies because of the interferences from red blood cell (RBC)
      components. However, this problem can be overcome by prior hemolysis of RBCs and
      a brief centrifugation to obtain white blood cells (WBCs), which can then be used
      for in vitro incubation with genotoxic compounds before comet assay. Overall,
      this whole-blood technique for comet assay is expected to provide a simple,
      rapid, and cost-effective alternative for the existing comet assay using isolated
      lymphocytes in situations such as when time and cost are limiting factors.

PMID- 15474414
TI  - Frequency of micronuclei in peripheral blood lymphocytes from subjects
      occupationally exposed to low levels of ionizing radiation.
AB  - The aim of this study was to evaluate the genotoxic effect of low dose of
      occupational radiation exposure in Nuclear Medicine Department employees, by
      using cytokinesis-blocked micronucleus assay in peripheral blood lymphocytes. The
      study included 46 exposed individuals together with 27 from the same area without
      occupational exposure to radiation which served as controls. The results obtained
      were evaluated with respect to age, gender, smoking habits, pathological
      condition and the occupational exposure to radiation of the individuals. The
      frequency of micronuclei increased significantly with the age of the subjects (P
      = 0.007). However there were no significant differences in micronucleus frequency
      with gender, smoking habits and occupational exposure. The frequency of
      micronuclei was significantly higher in individuals with presence of pathological
      condition (P < 0.0001) in comparison to healthy population irrespective of their
      exposure status.

PMID- 15474415
TI  - Anti-genotoxic and free-radical scavenging activities of extracts from (Tunisian)
      Myrtus communis.
AB  - The effect of extracts from leaves of Myrtus communis on the SOS reponse induced
      by Aflatoxin B1 (AFB1) and Nifuroxazide was investigated in a bacterial assay
      system, i.e. the SOS chromotest with Escherichia coli PQ37. Aqueous extract, the
      total flavonoids oligomer fraction (TOF), hexane, chloroform, ethyl acetate and
      methanol extracts and essential oil obtained from M. communis significantly
      decreased the SOS response induced by AFB1 (10 microg/assay) and Nifuroxazide (20
      microg/assay). Ethyl acetate and methanol extracts showed the strongest
      inhibition of the induction of the SOS response by the indirectly genotoxic AFB1.
      The methanol and aqueous extracts exhibited the highest level of protection
      towards the SOS-induced response by the directly genotoxic Nifuroxazide. In
      addition to anti-genotoxic activity, the aqueous extract, the TOF, and the ethyl
      acetate and methanol extracts showed an important free-radical scavenging
      activity towards the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. These results
      suggest the future utilization of these extracts as additives in chemoprevention
      studies.

PMID- 15474416
TI  - Transcription and DNA adducts: what happens when the message gets cut off?
AB  - DNA damage located within a gene's transcription unit can cause RNA polymerase to
      stall at the modified site, resulting in a truncated transcript, or progress
      past, producing full-length RNA. However, it is not immediately apparent why some
      lesions pose strong barriers to elongation while others do not. Studies using
      site-specifically damaged DNA templates have demonstrated that a wide range of
      lesions can impede the progress of elongating transcription complexes. The
      collected results of this work provide evidence for the idea that subtle
      structural elements can influence how an RNA polymerase behaves when it
      encounters a DNA adduct during elongation. These elements include: (1) the
      ability of the RNA polymerase active site to accommodate the damaged base; (2)
      the size and shape of the adduct, which includes the specific modified base; (3)
      the stereochemistry of the adduct; (4) the base incorporated into the growing
      transcript; and (5) the local DNA sequence.

PMID- 15474417
TI  - EXO1-A multi-tasking eukaryotic nuclease.
AB  - Exo1 was first isolated as a 5' --> 3' exonuclease activity induced during
      meiosis in fission yeast and since that time has been implicated in a multitude
      of eukaryotic DNA metabolic pathways that include DNA repair, recombination,
      replication, and telomere integrity. Involvement in multiple pathways affecting
      genomic stability makes EXO1 a logical target for mutation during oncogenesis.
      Here, we review studies in several experimental systems that shed light on the
      role of Exo1 in these DNA transaction pathways, particularly those that may
      relate to oncogenesis.

PMID- 15474418
TI  - DNA mismatch correction in Haemophilus influenzae: characterization of MutL, MutH
      and their interaction.
AB  - Haemophilus influenzae DNA mismatch repair proteins, MutS, MutL and MutH, are
      functionally characterized in this study. Introduction of mutS, mutL and mutH
      genes of H. influenzae resulted in complementation of the mismatch repair
      activity of the respective mutant strains of Escherichia coli to varying levels.
      DNA binding studies using H. influenzae MutH have shown that the protein is
      capable of binding to any DNA sequence non-specifically in a co-operative and
      metal independent manner. Presence of MutL and ATP in the binding reaction
      resulted in the formation of a more specific complex, which indicates that MutH
      is conferred specificity for binding hemi-methylated DNA through structural
      alterations mediated by its interaction with MutL. To study the role of conserved
      amino acids Ile213 and Leu214 in the helix at the C-terminus of MutH, they were
      mutated to alanine. The mutant proteins showed considerably reduced DNA binding
      and nicking, as well as MutL-mediated activation. MutH failed to nick HU bound
      DNA whereas MboI and Sau3AI, which have the same recognition sequence as MutH,
      efficiently cleaved the substrate. MutS ATPase activity was found to be reduced
      two-fold in presence of covalently closed circular duplex containing a mismatched
      base pair whereas, the activity was regained upon linearization of the circular
      duplex. This observation possibly suggests that the MutS clamps are trapped in
      the closed DNA heteroduplex. These studies, therefore, serve as the basis for a
      detailed investigation of the structure-function relationship among the protein
      partners of the mismatch repair pathway of H. influenzae.

PMID- 15474419
TI  - Role of mismatch-specific uracil-DNA glycosylase in repair of 3,N4-ethenocytosine
      in vivo.
AB  - The 3,N(4)-ethenocytosine (epsilon C) residue might have biological role in vivo
      since it is recognized and efficiently excised in vitro by the E. coli mismatch
      specific uracil-DNA glycosylase (MUG) and the human thymine-DNA glycosylase
      (hTDG). In the present work we have generated mug defective mutant of E. coli by
      insertion of a kanamycin cassette to assess the role of MUG in vivo. We show that
      human TDG complements the enzymatic activity of MUG when expressed in a mug
      mutant. The epsilon C-DNA glycosylase defective strain did not exhibit
      spontaneous mutator phenotype and did not show unusual sensitivity to any of the
      following DNA damaging treatments: methylmethanesulfonate, N-methyl-N'-nitro-N
      nitrosoguanidine, ultraviolet light, H(2)O(2), paraquat. However, plasmid DNA
      damaged by 2-chloroacetaldehyde treatment in vitro was inactivated at a greater
      rate in a mug mutant than in wild-type host, suggesting that MUG is required for
      the in vivo processing of the ethenobases. In addition, 2-chloroacetaldehyde
      treatment induces preferentially G.C --> C.G and A.T --> T.A transversions in mug
      mutant. Comparison of the mutation frequencies induced by the site-specifically
      incorporated epsilon C residue in E. coli wild-type versus mug indicates that MUG
      repairs more than 80% of epsilon C residues in vivo. Furthermore, the results
      show that nucleotide excision repair and recombination are not involved in the
      processing of epsilon C in E. coli. Based on the mutagenesis data we suggest that
      epsilon C may be less toxic and less mutagenic than expected. The increased
      spontaneous mutation rate for G.C --> A.T transition in the ung mug double mutant
      as compared to the single ung mutant suggest that MUG may be a back-up repair
      enzyme to the classic uracil-DNA glycosylase.

PMID- 15474421
TI  - Cell cycle regulation of the murine 8-oxoguanine DNA glycosylase (mOGG1): mOGG1
      associates with microtubules during interphase and mitosis.
AB  - 8-Oxoguanine DNA glycosylase (OGG1) is a major DNA repair enzyme in mammalian
      cells. OGG1 participates in the repair of 8-oxoG, the most abundant known DNA
      lesion induced by endogenous reactive oxygen species in aerobic organisms. In
      this study, antibodies directed against purified recombinant human OGG1 (hOGG1)
      or murine (mOGG1) protein were chemically conjugated to either the
      photosensitizer Rose Bengal or the fluorescent dye Texas red. These dye-protein
      conjugates, in combination with binding assays, were used to identify
      associations between mOGG1 and the cytoskeleton of NIH3T3 fibroblasts. Results
      from these binding studies showed that mOGG1 associates with the cytoskeleton by
      specifically binding to the centriole and microtubules radiating from the
      centrosome at interphase and the spindle assembly at mitosis. Similar results
      were obtained with hOGG1. Together results reported in this study suggest that
      OGG1 is a microtubule-associated protein itself or that OGG1 utilizes yet to be
      identified motor proteins to ride on microtubules as tracks facilitating the
      movement and redistribution of cytoplasmic OGG1 pools during interphase and
      mitosis and in response to oxidative DNA damage.

PMID- 15474420
TI  - DNA decay and limited Rad53 activation after liquid holding of UV-treated
      nucleotide excision repair deficient S. cerevisiae cells.
AB  - The DNA damage checkpoint is a surveillance mechanism activated by DNA lesions
      and devoted to the maintenance of genome stability. It is considered as a signal
      transduction cascade, involving a sensing step, the activation of a set of
      protein kinases and the transmission and amplification of the damage signal
      through several phosphorylation events. In budding yeast many players of this
      pathway have been identified. Recent work showed that G1 and G2 checkpoint
      activation in response to UV irradiation requires prior recognition and
      processing of UV lesions by nucleotide excision repair (NER) factors that likely
      recruit checkpoint proteins near the damage. However, another report suggested
      that NER was not required for checkpoint function. Since the functional
      relationship between repair mechanisms and checkpoint activation is a very
      important issue in the field, we analyzed, under different experimental
      conditions, whether lesion processing by NER is required for checkpoint
      activation. We found that DNA damage checkpoint can be triggered in an NER
      independent manner only if cells are subjected to liquid holding after UV
      treatment. This incubation causes a time-dependent breakage of DNA strands in NER
      deficient cells and leads to partial activation of the checkpoint kinase. The
      analysis of the genetic requirements for this alternative activation pathway
      suggest that it requires Mec1 and the Rad17 complex and that the observed DNA
      breaks are likely to be due to spontaneous decay of damaged DNA.

PMID- 15474422
TI  - Database of mouse strains carrying targeted mutations in genes affecting
      biological responses to DNA damage (Version 6).
AB  - We present Version 6 of a database of mouse mutant strains that affect biological
      responses to DNA damage. This database is also electronically available at
      http://pathcuric1.swmed.edu/research/research.htm.

PMID- 15474423
TI  - The evolution of breast surgery: where technology and compassion meet.
AB  - The origins and development of The American Society of Breast Surgeons are
      closely tied to technology. Innovative technical progress means less-invasive
      procedures, more precise diagnoses, more outpatient services, and--with all of
      this--less pain and stress for our patients. It means more compassionate breast
      care for women. The Society's mission revolves around improving all aspects of
      patient care, and this is where technology and compassion meet.

PMID- 15474424
TI  - Cryoablation treatment of benign breast lesions with 12-month follow-up.
AB  - OBJECTIVE: Eighty percent of all breast biopsies reveal benign findings. The most
      common benign tumor is a fibroadenoma. Despite their benign nature, many women
      eventually choose to have their bothersome lumps surgically removed. We report
      the use of cryoablation to treat these benign breast lesions with minimum 12
      month follow-up. METHODS: After receiving Institutional Review Board approval, a
      prospective nonrandomized trial was initiated in June 2000. Ultrasound-guided
      cryoablation of core biopsy-proven benign fibroadenomas, other benign breast
      nodules, or nodular fibrocystic change was performed on 78 lesions in 63
      patients. Eighty-five percent of lesions treated were benign fibroadenomas. The
      cryoablation procedure consisted of a double freeze-thaw cycle that lasted
      between 6 and 30 minutes and was performed most often in an office setting. Each
      patient was serially evaluated for treatment efficacy, complications, and patient
      satisfaction. RESULTS: Sixty-four of 78 lesions (mean size 2.0 cm [range 0.8 to
      4.2]) were followed-up for at least 12 months after cryoablation per protocol,
      which included 53 fibroadenomas. At 1 year, ultrasound tumor volume resorption
      was 88.3% overall (87.3% for fibroadenomas), and 73% of the entire group became
      nonpalpable to both clinician and patient (75% for fibroadenomas). Two of the
      fibroadenoma patients had their palpable residual nodule excised, both revealing
      necrotic debris and no viable tumor in the treated volume. Serial mammograms
      showed resorption of the lesion leaving minimal residual density without
      calcifications. Cosmesis was excellent with only a small scar remaining at the
      probe insertion site. There was no report of visual or palpable volumetric
      deficit. Patient satisfaction was good to excellent in 92% of cases. CONCLUSIONS:
      Cryoablation was successful in treating core biopsy-proven benign breast lesions
      in 63 patients. At 12 months, we found gradual resorption of treated tissue with
      no cosmetic deficit. Ultrasound-guided cryoablation is an effective and safe
      treatment for benign breast lesions, as seen at 12-month follow-up, and offers an
      office-based, minimally invasive alternative to surgical excision.

PMID- 15474425
TI  - Local recurrence in lumpectomy patients after imprint cytology margin evaluation.
AB  - BACKGROUND: This is a follow-up study to our previously reported data on local
      recurrence rates in patients whose lumpectomy margins were evaluated by
      intraoperative imprint cytology (IIC(M)). The purpose of this study was to
      compare local recurrence rates for patients whose lumpectomy margins were
      evaluated with IIC(M) with local recurrence rates of those not evaluated by
      IIC(M). METHODS: A total of 1713 patients underwent lumpectomy treatment for
      breast cancer from 1988 to 2001 were prospectively entered into a computerized
      database and subsequently included in this study. Of the patients, 520 (group 1)
      had their surgery performed at an outside institution where conventional margin
      analysis was performed. Another 1193 (group 2) had their surgery performed at our
      institution where margins were evaluated by IIC(M). For each histologic type and
      for the overall sample, probabilities of recurrence with time were estimated
      using the method of Kaplan and Meier. RESULTS: IIC(M) overcomes sampling error
      inherent in the frozen section analysis and results in a diminished incidence of
      overall 5-year local recurrence from 8.8% to 2.8% (P <0.0001). The recurrence
      rates for each respective histologic subtype are reported for both absolute
      recurrences and probability of recurrence with time. CONCLUSIONS: IIC(M) provides
      an accurate evaluation of lumpectomy margins for patients undergoing breast
      conservation treatment. IIC(M) was associated with an overall lower local
      recurrence rate. This series defined the utility of intraoperative imprint
      cytology for evaluation of margins in patients undergoing breast-conservation
      treatment.

PMID- 15474426
TI  - Partial breast irradiation in breast conserving therapy by way of intersitial
      brachytherapy.
AB  - OBJECTIVE: To examine early and late toxicities, evaluate cosmetic results, and
      determine the need for reoperation or additional diagnostic procedures in
      patients treated with accelerated partial breast irradiation (APBI) delivered by
      way of an interstitial implant in breast-conserving therapy. METHODS: A total of
      199 patients with stage I or II breast cancer were managed with lumpectomy
      followed by radiation restricted to the tumor bed using an interstitial implant
      (APBI). Retrospective analyses were performed for early and late toxicities
      (infection, fat necrosis, breast pain, edema, erythema, fibrosis, pigmentation
      changes, and telangiectasias), need for reoperation or additional diagnostic
      procedures, cosmetic results, and local control. Patient selection criteria by
      the surgeon for referral to RT for APBI included age, tumor size, histology,
      nodal status, margin status, and absence of extensive intraductal component.
      Treatment was delivered with either a low-dose or high-dose rate implant. Median
      follow-up was 5.7 years, and 54% of the patients were followed-up for >7 years.
      RESULTS: Infections developed in 22 of 199 (11%) patients: 7% early (</=1 month
      after implant removal) and 4% late (>1 month after implant removal). Five of the
      22 patients (2% of all patients) required operative intervention for the
      infection, either incision and drainage or debridement. There was a statistically
      significant difference between infection rates with open (8.5%) versus closed
      (2.5%) cavity placement of the interstitial needles (P = 0.005). There was no
      statistically significant difference between low-dose rate (inpatient) and high
      dose rate (outpatient) treatment (P = 0.207). Forty-five patients (23%) had an
      additional diagnostic procedure to evaluate a suspicious or uncertain finding on
      physical examination or mammogram. Fibrosis and fat necrosis were found in 26 of
      the 45 patients. The incidence of fat necrosis increased with time. More patients
      were found to have fat necrosis after 5 years. One patient had fat necrosis
      diagnosed at <6 months; 8 patients (4% of total) at >/=6 months to <2 years; 10
      patients (5% of total) at >/=2 years to <5 years; and 22 patients (11% of total)
      at >/=5 years. The majority of fat necrosis was detected on mammogram (80%) and
      was asymptomatic (78%). Cosmesis and toxicities were assessed at 3 defined time
      points: </=6 months, 2 years, and >/=5 years of follow-up. Using Harvard
      criteria, good to excellent cosmetic results were observed in >90% of patients.
      Breast pain, edema, and erythema diminished with time. Of the 199 cases, there
      were only 5 ipsilateral breast failures, yielding a 5-year actuarial local
      recurrence rate of 1.2%. Of these 5 failures, 2 were true recurrences/marginal
      misses, yielding a 5-year actuarial true recurrence/marginal miss rate of 0.5%.
      The 5-year actuarial cause-specific survival rate was 99% for APBI patients.
      CONCLUSIONS: In selected patients with early-stage breast cancer, APBI with
      targeted interstitial brachytherapy offers 5-year results comparable with
      conventional breast-conserving therapy employing whole-breast radiation therapy.
      Minimal long-term toxicities were noted, most of which demonstrated continued
      resolution over time. Acceptable acute (7%) and delayed (4%) infection rates were
      observed. Fat necrosis was identified with increasing frequency with time, but
      the majority was asymptomatic. Cosmetic results are good to excellent (>90%).
      Continued follow-up by the surgeon will be required to determine the long-term
      efficacy of this alternative treatment approach.

PMID- 15474427
TI  - Association of breast cancer with papillary lesions identified at percutaneous
      image-guided breast biopsy.
AB  - BACKGROUND: The management of papillary lesions identified on image-guided breast
      biopsy remains controversial. In the literature, data regarding papillary lesions
      are limited because of small sample sizes. The purpose of this study was to
      identify the prevalence of atypical ductal hyperplasia and malignancy associated
      with papillary lesions identified on image-guided breast biopsy. METHODS: This
      study is a retrospective review of 9,310 consecutive image-guided biopsies
      performed at our institution between January 1996 and November 2003. Patients
      were included if they underwent an excisional biopsy after a papillary lesion was
      diagnosed on image-guided biopsy. RESULTS: Papillary lesions were identified in
      153 (2%) of the 9,310 image-guided biopsies performed, and 87 of these patients
      underwent subsequent excisional biopsy at our institution. Breast cancer (in situ
      or invasive) was identified in 15 patients (17%), and 16 patients (18%) had
      atypical ductal hyperplasia identified at excisional biopsy. CONCLUSIONS: These
      data suggest that excisional biopsy should be considered when a papillary lesion
      is identified at percutaneous image-guided breast biopsy. The final surgical
      pathology may impact the treatment plan, risk reduction, and/or surveillance for
      more than a third of patients diagnosed with a papillary lesion on image-guided
      biopsy.

PMID- 15474428
TI  - Outcome after invasive recurrence in patients with ductal carcinoma in situ of
      the breast.
AB  - BACKGROUND: Local recurrence is used as a marker of treatment failure for
      patients with ductal carcinoma in situ (DCIS). As follow-up lengthens, distant
      recurrence, breast cancer-specific survival (BCSS), and overall survival must be
      monitored. METHODS: A prospective database was used to analyze 1031 patients with
      DCIS. Patients having invasive recurrence after DCIS treatment were compared with
      patients having infiltrating ductal carcinoma (IDC). End points included distant
      recurrence, BCSS, and overall survival. RESULTS: Overall, patients with DCIS had
      a BCSS of 99%. BCSS was 85% for patients with invasive recurrences. DDFS in this
      group was 80%. Stage I IDC patients had a BCSS of 91%, whereas it was 38% in
      those with stage I IDC and invasive recurrences. CONCLUSIONS: Most patients with
      DCIS that recur can be salvaged. For the small subgroup of patients who recur
      with invasive breast cancer, survival is similar to that of patients with stage
      IIA IDC.

PMID- 15474429
TI  - Radioactive seed localization of nonpalpable breast lesions is better than wire
      localization.
AB  - BACKGROUND: The current study sought to validate radioactive seed localization
      (RSL) as an alternative to wire localization (WL) to facilitate the operative
      excision of nonpalpable breast lesions. METHODS: One hundred consecutive patients
      underwent preoperative WL and the next 100 RSL. Margins were considered negative
      if > or =2 mm from in situ and invasive disease. RESULTS: RSL resulted in 100%
      retrieval of the seeds and lesions. Sixty-eight percent of patients underwent RSL
      at least 1 day before surgery. RSL resulted in a 35% relative improvement in the
      rate of negative margins in the first specimen (P = 0.01) and a 62% relative
      improvement in the rate of reoperation for positive margins (P = 0.01). The
      sentinel lymph node (SLN) identification rate was 100% in both groups.
      CONCLUSIONS: RSL is effective and safe, and this procedure significantly improved
      the rate of negative margins in the first specimen and the rate of reoperation
      for positive margins compared to WL. We highly favor RSL over WL.

PMID- 15474430
TI  - Ultrasound is now better than mammography for the detection of invasive breast
      cancer.
AB  - OBJECTIVE: This study investigated the use of ultrasound (US) as a first-line
      diagnostic tool. METHODS: All women attending our breast center underwent
      bilateral whole-breast US in addition to all other investigations, and results
      were documented prospectively and preoperatively. RESULTS: Of 796 patients with
      breast cancer, US was positive in 710 (89%) and mammography in 706 (89%) (P = not
      significant). Either US or mammogram was positive in 770 (97%). Of 537 (67%)
      symptomatic patients, US was positive in 497 (93%) and mammography in 465 (87%).
      Either US or mammography was positive in 515 (96%). Of 259 (33%) screening
      patients, 220 (85%) had invasive cancer. US was positive in 195 (89%) and
      mammography in 203 (92%) (P = not significant). Either US or mammography was
      positive in 217 (99%). Of 39 screening patients with ductal carcinoma in situ (5%
      of all patients), US was positive in 18 (46%) and mammography in 38 (97%).
      CONCLUSIONS: US is significantly better than mammography for detecting invasive
      breast cancer (92% patients). The combination of US and mammography is
      significantly better than either modality used alone, together resulting in 9%
      more breast cancers detected.

PMID- 15474431
TI  - High-resolution axillary ultrasound is a poor prognostic test for determining
      pathologic lymph node status in patients undergoing neoadjuvant chemotherapy for
      locally advanced breast cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of high
      resolution axillary ultrasound in detecting axillary lymph node metastases after
      neoadjuvant chemotherapy in patients with locally advanced breast cancer.
      METHODS: Fifty-three patients with stage II or III breast cancer undergoing
      neoadjuvant chemotherapy who had a physical examination, high-resolution axillary
      ultrasound, and axillary lymph node dissection from January 1999 to September
      2003 were included in this study. RESULTS: The positive predictive value of the
      postchemotherapy ultrasound for predicting pathologic nodal involvement was 83%,
      but the negative predictive value was only 52%. Postchemotherapy physical
      examination was also poor at predicting pathologic nodal involvement with a
      positive predictive value of 93% and a negative predictive value of only 58%.
      CONCLUSIONS: A negative post-neoadjuvant chemotherapy high-resolution axillary
      ultrasound or physical examination does not predict pathologic node status, and
      this test has limited value in this setting.

PMID- 15474432
TI  - Patient and duct selection for nipple duct lavage.
AB  - BACKGROUND: Nipple ductal lavage (NDL) is a new minimally invasive procedure with
      the potential to help identify women who could benefit from breast cancer risk
      intervention. NDL is currently encouraged for women with fluid-producing ducts
      and a 5-year Gail risk > or =1.7%. The purpose of this study was to evaluate the
      atypia rate by NDL in fluid-producing ducts compared with non-fluid-producing
      ducts and the atypia rate in high-risk verses low-risk patients to determine if
      current recommendations are supported. METHODS: Fifty-nine women were studied
      with NDL. The 226 ducts lavaged included all fluid-producing ducts (n = 136) and
      any dry ducts we could cannulate (n = 90). Breast cancer risk was calculated
      using mathematic models. RESULTS: There were 26 (44%) women with a 5-year Gail
      risk > or =1.7% and 33 (56%) with a 5-year Gail risk <1.7%. Cytologic atypia was
      diagnosed in 20 of 59 (34%) of patients. The atypia rate was similar for women
      with a 5-year Gail risk > or =1.7% (9 of 26 or 35%) compared with lower-risk
      women (11 of 33 or 33%, P = 1.0) and for fluid-producing ducts (26 of 136 or 19%)
      compared with dry ducts (14 of 90 or 15%, P = 0.61). No significant differences
      were found when the atypia was categorized as mild versus marked. Of note, the
      insufficient sample rate was higher for dry ducts (33%) compared with fluid
      producing duct (22%, P = 0.07). CONCLUSIONS: If NDL results are found to
      correlate with breast cancer incidence, it will be important to apply the test in
      a way that maximizes sensitivity for the detection of atypia in a screened
      population. We were unable to identify patient or duct characteristics that
      predict NDL atypia rates.

PMID- 15474433
TI  - A retrospective study of columnar alteration with prominent apical snouts and
      secretions and the association with cancer.
AB  - BACKGROUND: Columnar alteration with prominent snouts and secretions (CAPSS) is
      routinely described on breast core needle biopsies (CNBs); however, its
      significance and appropriate treatment is unknown. This study evaluated the
      incidence of cancer (in situ/invasive) in core biopsies and in subsequent
      surgical biopsy specimens after an initial core biopsy identifying CAPSS.
      METHODS: Using our medical center's pathology database, we retrospectively
      identified lesions described as CAPSS on breast core needle biopsies performed
      between January 1998 and August 2003. The specimens were subdivided into CAPSS
      lesions with and without atypical features. We also identified lesions described
      as atypical ductal hyperplasia. RESULTS: Overall, 10 cancers were associated with
      135 (7.4%) CAPSS lesions without atypia, and 11 (18.3%) were associated with 60
      CAPSS lesions with atypia (P = 0.023). CAPSS lesions with atypical features had a
      slightly higher rate of coexisting cancer on initial biopsy than CAPSS without
      atypical features (7% vs 12%, P = 0.320). Specimens showing atypical ductal
      hyperplasia on initial biopsy had a greater rate of coexisting cancer than CAPSS
      with or without atypical features (P <0.0001). CONCLUSION: We support the
      existing recommendation that a patient with a CNB showing CAPSS with atypical
      features undergo surgical biopsy.

PMID- 15474434
TI  - Lumpectomy margins are affected by tumor size and histologic subtype but not by
      biopsy technique.
AB  - OBJECTIVE: The effect of the type of biopsy (needle vs. excisional) on lumpectomy
      margin status has not been well established. The objective of this study was to
      determine whether needle biopsy is associated with a higher positive margin rate
      at time of lumpectomy. METHODS: We evaluated this hypothesis in the setting of a
      prospective multi-institutional study. A total of 3975 patients were enrolled in
      the University of Louisville Breast Cancer Sentinel Lymph Node Study from May 7,
      1998 to June 3, 2003. Patients who underwent lumpectomy at the time of their
      sentinel lymph node biopsy were the focus of this analysis. Patients with
      clinical stage T1 N0 and T2 N0breast cancer were eligible; 29 patients were found
      to have T3 tumors on final pathology. Pathologists at each institution defined
      margin positivity, and tumor at the inked margin of resection was the study
      guideline. RESULTS: Median patient age was 59 years, and median tumor size was
      1.5 cm. A total of 2658 patients underwent lumpectomy with the following results.
      The cancer of 1515 patients was diagnosed by fine-needle or core-needle biopsy
      and of 821 patients was diagnosed by excisional biopsy; in 322 patients the
      method of diagnosis was unknown. The type of previous biopsy did not
      significantly affect the positive-margin rate at the time of lumpectomy (13.3%
      vs. 11.0% for needle and excisional biopsy, respectively, P = 0.107). However,
      patients with larger tumors were more often found to have a positive margin
      (11.4% vs. 13.9% vs. 27.6% for T1, T2, and T3 tumors, respectively; P = 0.010).
      No difference was found in margin status after excision of palpable versus
      nonpalpable tumors (10.6% vs. 10.9%, respectively, P = 0.743). Histologic
      subtype, however, did affect margin status (15.8% vs. 9.8% positive margins for
      lobular vs. ductal type, respectively, P = 0.003). CONCLUSIONS: In this multi
      institutional study, increasing tumor size and lobular histologic subtype were
      associated with a greater likelihood of a positive margin. The type of biopsy,
      needle or excisional, had no effect on the ability to achieve negative margins.

PMID- 15474435
TI  - Two-year follow-up of areola-sparing mastectomy with immediate reconstruction.
AB  - OBJECTIVE: Areola-sparing mastectomy (ASM) is defined as resecting the nipple and
      any existing surgical biopsy scar, removing all breast parenchyma, and leaving a
      natural envelope of skin (including the areola), which improves the aesthetic
      result of immediate reconstruction. We previously demonstrated a <1% incidence of
      malignant involvement of the areola in a retrospective mastectomy series.
      Subsequently, we performed ASM on selected patients undergoing mastectomy. We
      report here our results from an ongoing study of ASM at our institution. METHODS:
      During a 20-month period, 17 ASMs with immediate reconstruction were performed on
      12 patients. Patients were followed-up prospectively by the surgical oncologist
      for complications and recurrence. RESULTS: ASM was performed for breast cancer
      prophylaxis (n = 10), ductal carcinoma in situ (DCIS) (n = 4), and <2-cm
      peripheral infiltrating carcinoma (n = 3). The mean patient age was 47.7 years
      (range 37 to 61). Thirteen patients were reconstructed with tissue expanders and
      4 with pedicle transverse rectus abdominus myocutaneous flaps. Ten patients
      underwent sentinel lymph node biopsy. None of the ten patients showed sentinel
      lymph node metastasis. Two patients with DCIS and microinvasion underwent
      subareolar touch-prep cytology, both of which were negative for malignancy. All
      mastectomy specimens had negative histologic margins. No patient received
      chemotherapy or radiation therapy. One postoperative consisted of a localized
      wound infection that resolved with oral antibiotics. At a median follow-up of 24
      months (range 11 to 28), there were no instances of local or distant recurrence.
      CONCLUSIONS: Overall, we found that ASM with immediate reconstruction provides
      excellent aesthetic results with infrequent complications. Furthermore, in this
      small series we showed no recurrence at 2 years. We continue to offer ASM for
      selected patients including those desiring surgical breast cancer prophylaxis as
      well as those with DCIS or small peripheral infiltrating ductal carcinoma.

PMID- 15474436
TI  - Twenty-two year experience with recurring subareolar abscess andlactiferous duct
      fistula treated by a single breast surgeon.
AB  - BACKGROUND: Recurring subareolar abscess and lactiferous duct fistula are
      frequently difficult to manage. METHODS: Personal experience with 67 cases
      treated during the past 22 years is reviewed. RESULTS: There were 38 cases of
      subareolar abscess and 29 of lactiferous duct fistula. Thirty-three patients had
      resolution with antibiotics and needle aspiration or with incision and
      drainage,but 34 patients required definitive duct excision. Eight patients had
      duct excision through circumareolar incisions, and 5 of these had prolonged
      healing problems or recurrence within 1 year. Twenty-six patients had duct
      excision by placing a probe into the duct and radially excising an elliptical
      area of the nipple and areola like a "slice of pie," and these all healed
      primarily (P <0.001). CONCLUSIONS: Approximately half of the patients with
      subareolar abscess can be managed medically, but the other half will require
      definitive duct excision. A radial elliptical incision with primary closure
      results in excellent cosmesis and low long-term recurrence rates.

PMID- 15474437
TI  - Prospective study of intraoperative mammary ductoscopy in patients undergoing
      partial mastectomy for breast cancer.
AB  - BACKGROUND: The purpose of this study was to critically evaluate the added
      benefit of intraoperative mammary ductoscopy on margin assessment and
      identification of occult intraductal pathology in patients undergoing therapeutic
      partial mastectomy for in-situ and invasive breast carcinoma. METHODS: Eligible
      patients underwent intraoperative mammary ductoscopy before partial mastectomy.
      In patients where an intraductal abnormality was identified and the mammary
      ductoscope was not within the partial mastectomy cavity, an additional ductoscopy
      directed margin of tissue was analyzed. RESULTS: Nineteen of 30 (63%) patients
      yielded nipple aspirate fluid and were able to undergo mammary ductoscopy; an
      intraductal abnormality was identified in 15 of 19 (79%) patients. Only 1 patient
      had an occult infiltrating carcinoma, which was outside of the resection cavity
      and identified by ductoscopy. CONCLUSIONS: Although mammary ductoscopy can
      identify intraductal abnormalities during partial mastectomy in a significant
      number of patients, many of these findings may be either benign or within the
      standard field of resection, thus adding no benefit to the patient.

PMID- 15474438
TI  - Office-based breast ductoscopy for diagnosis.
AB  - OBJECTIVE: Ductoscopy is an evolving technology that has been used primarily and
      historically in conjunction with open surgical procedures. New technical
      improvements allow intraductal biopsy and therefore its application in the
      clinical setting for diagnostic evaluations of the breast. This study looks at
      the initial use of intraductal biopsy in a variety of settings from an academic
      university practice to a private single-surgeon office. METHODS: This is a
      multicenter retrospective series of 88 patients undergoing ductoscopy of > or =1
      duct for the diagnostic workup of common breast problems. The procedures were
      done with the patient under local anesthesia, and intraductal biopsy specimens
      were taken and analyzed as breast cytology samples. RESULTS: Of the 88 patients
      undergoing office ductoscopy, nipple discharge was the most common indication (n
      = 83 patients; 94% to 66% spontaneous and 34% elicited). Fifty-five percent were
      high risk for breast cancer by history. The majority of patients had normal
      previous mammograms: 48 Breast Imaging-Reporting and Data System (BIRADS) 1, 24
      BIRADS 2, and 7 BIRADS 3 to 5. The most common finding was papilloma present in
      29 (32%) patients by endoscopy. Only 31% of patients had a history of brown or
      bloody nipple discharge. A wide variety of other endoscopic abnormalities were
      seen and biopsied. The average number of biopsies per patient was 2 with 18
      (20.5%) having severe or malignant atypia. Further follow-up and management of
      these more concerning abnormalities is currently ongoing. CONCLUSIONS: These
      results indicate that office ductoscopy with biopsy is both feasible and does
      identify suspicious or malignant atypia in patients with expressed or spontaneous
      nipple fluid.

PMID- 15474439
TI  - Cytokeratin staining for intraoperative evaluation of sentinel lymph nodes in
      patients with invasive lobular carcinoma.
AB  - BACKGROUND: Frozen section and intraoperative imprint cytology (IIC(N)) are 2
      methods used for intraoperative pathologic assessment of sentinel lymph nodes
      (SLNs). The SLN evaluation of patients with invasive lobular carcinoma (ILC)
      results in a relatively high number of false-negative results using either of
      these methods. The purpose of this study was to evaluate the added benefits that
      intraoperative immunohistochemical-cytokeratin staining (I(CK-IHC)) can bring to
      IIC(N) in the evaluation of SLN in patients with ILC. METHODS: A total of 59
      breast cancer patients with ILC underwent an SLN biopsy evaluated by our standard
      IIC(N) assessment in addition to I(CK-IHC). The results of IIC(N) with I(CK-IHC)
      were compared with the final histopathologic assessment consisting of standard
      hematoxylin and eosin staining and additional cytokeratin staining of nodes.
      RESULTS: Intraoperative evaluation of SLN using IIC(N) and I(CK-IHC) correctly
      diagnosed the nodal status in 45 of 59 (76.3%) patients. On final histopathologic
      assessment, 31 of 59 (52.5%) patients were found to have positive nodes. Using
      I(CK-IHC), 17 of these 31 positive cases (54.8%) were detected. Using IIC(N)
      alone, without the benefit of I(CK-IHC), only 13 of 31 (41.9%) positive cases
      were detected intraoperatively. CONCLUSIONS: For patients with ILC, I(CK-IHC)
      staining in addition to IIC(N) improves accuracy over using IIC(N) alone. In this
      study, I(CK-IHC) staining demonstrated a 12.9% improvement in the detection of
      SLN metastases in patients with ILC. Cytopathologists should consider employing
      I(CK-IHC) staining to evaluate the touch-imprint slides of SLN in ILC patients.

PMID- 15474440
TI  - A concordance study of subareolar and subdermal injections for breast cancer
      sentinel lymph node mapping.
AB  - BACKGROUND: There is disagreement regarding the preferred injection site for
      breast sentinel lymph node mapping. METHODS: The concordance of blue staining and
      radioactivity in the sentinel nodes of 730 consecutive patients was analyzed
      based on injection of mapping agents into the same or separate intradermal and
      subareolar sites. RESULTS: There were no significant differences in
      identification rates or the mean number of sentinel nodes whether agents were
      injected into the same or separate sites. In each group, a concordant sentinel
      node (both blue and "hot") was identified in >90% of patients (P = not
      significant). There were no significant differences in the percentage of sentinel
      nodes identified as both blue and hot. CONCLUSIONS: Separate subdermal and
      subareolar injections of mapping agents drain to the same sentinel node as often
      as injections into the same location. These two injection techniques appear to
      result in the identification of the same sentinel nodes.

PMID- 15474441
TI  - Understanding the biologic mechanisms responsible for breast-cancer progression
      during tamoxifen or fulvestrant treatment.
AB  - BACKGROUND: Dehydroepiandosterone sulfate (DHEAS) causes breast-cancer
      proliferation, even during tamoxifen or fulvestrant blockade. The purpose of this
      study was to determine possible mechanisms for this treatment failure. METHODS: T
      47D cells (estrogen receptor [ER] and progesterone receptor [PR] positive) were
      treated with fulvestrant (10 micromol/L), tamoxifen (10 mmol/L or 0.0001 nmol/L),
      or vehicle and stimulated with DHEAS. Gene expression of ER, PR, insulin-like
      growth factor (IGF)-1 and -2, and insulin-like growth-factor binding protein
      (IGFBP)-1 through -4 was determined. RESULTS: ER and PR gene expression decreased
      by 1.3- and 4-fold with fulvestrant and DHEAS. ER expression decreased by 2.7
      fold with 0.0001 nmol/L tamoxifen and DHEAS. ER and PR expression were unchanged
      by 10 nmol/L tamoxifen. IGF-1 and IGF-2 were not expressed. IGFBP-2 and -4
      expression decreased by 1.9- and 1.6-fold after DHEAS stimulus, although this was
      not statistically significant. CONCLUSIONS: DHEAS exposure, even in the presence
      of tamoxifen and fulvestrant, induces changes in ER and PR gene expression that
      may be partially responsible for breast cancer progression.

PMID- 15474442
TI  - Selective intraoperative consultation for the evaluation of sentinel lymph nodes
      in breast cancer.
AB  - BACKGROUND: Routine intraoperative evaluation of sentinel lymph nodes (SLNs) in
      breast cancer suffers from lack of sensitivity and consumes both time and
      resources. Failure to perform immediate consultation requires node-positive
      patients to return for delayed dissection. METHODS: We sought to determine
      whether selective use of intraoperative pathology consultation (IOC), based on
      the surgeon's clinical suspicion for metastases, would be accurate, avoid
      unnecessary consultations, and have a similar rate of delayed axillary
      dissection. We performed a retrospective chart review of two cohorts of
      clinically node-negative patients with invasive breast cancer undergoing axillary
      lymph node dissection (ALND). Selective pathology evaluation was performed in the
      study group and mandatory evaluation in the control group. RESULTS: The axillary
      basins of 327 patients undergoing routine IOC were compared with those of 91
      patients in whom selective IOCs were requested. Twenty-eight consultations (31%)
      were obtained in the selective group. Selective consultation changed
      intraoperative management in 11 of 28 patients (39%) compared to 46 of 327 (14%)
      in the routine group (P = 0.005). The mean SLN metastasis size was 9.6 mm
      compared to 1.5 mm in patients in whom consultation was deferred (P = 0.003). The
      need for delayed ALND (17% vs. 14%) was similar in both groups, and was
      determined by occult metastases that were not detected by either method.
      CONCLUSIONS: Selective use of IOC detects the majority of SLN macrometastases,
      avoids consultation that does not alter intraoperative management, and is not
      associated with an increased need for delayed ALND.

PMID- 15474443
TI  - Analysis of the use of specimen mammography in breast conservation therapy.
AB  - BACKGROUND: Obtaining tumor-negative margins when performing breast-conserving
      surgery is the standard of care to prevent local recurrence. We believe two-view
      specimen mammography is a useful method for intraoperative determination of
      adequacy of excision. METHODS: A retrospective review was performed on patients
      who underwent wire-localized partial mastectomy for invasive cancer in our Breast
      Center from 2000 to 2001. Two-view specimen mammography reports were compared to
      the pathologic evaluation. RESULTS: Eighty-eight of 93 patients (95%) had
      complete primary excision. Sixteen patients had additional margins excised at the
      time of the initial operation based on specimen mammogram. Six patients would
      have had positive margins had additional excision at the primary surgery not been
      performed. CONCLUSIONS: Specimen mammography can help reduce reoperation rate by
      identifying patients who need additional margin excision at the time of initial
      surgery for breast conservation therapy. Using two-view specimen mammography, our
      reoperation rate was reduced from 12% to 5%.

PMID- 15474444
TI  - Trends in breast cancer presentation and care according to age in a single
      institution.
AB  - BACKGROUND: This study sought to determine the differences in presentation and
      treatment of young women (< or =40 years of age) with breast cancer. METHODS: A
      prospective database was analyzed for differences in presentation and care in
      breast cancer patients < or =40 and >40 years of age. RESULTS: The study group
      consisted of 1685 women. Younger women were more likely to present with a
      palpable mass, have estrogen receptor/progesterone receptor (ER/PR)-negative
      tumors, and have more advanced disease at presentation. Although there was no
      difference in breast conservation rates, younger women were more likely to have
      postmastectomy reconstruction. Younger women were more likely to receive
      chemotherapy, even with node-negative tumors less than 1 cm in diameter (37% vs.
      13%, P = 0.01). CONCLUSIONS: The presentation of younger women with breast cancer
      differs from that of older women. Although the surgical management is similar,
      adjuvant therapy differs, with younger women more likely to be treated with
      chemotherapy.

PMID- 15474445
TI  - The value of sentinel lymph node biopsy in elderly breast cancer patients.
AB  - BACKGROUND: Although sentinel lymph node biopsy has been accepted as a useful
      procedure for certain breast cancer patients, the value of this procedure in the
      elderly remains unknown. We undertook this study to evaluate changes in adjuvant
      treatment attributable to sentinel lymph node biopsy. METHODS: A total of 104
      patients > or =65 years underwent sentinel lymph node biopsy plus lumpectomy or
      mastectomy for the treatment of clinically node-negative invasive breast cancer.
      Demographic, pathologic, and treatment data were evaluated using an SAS software
      package (SAS, Cary, North Carolina). RESULTS: Twenty-nine of 104 patients (28%)
      had metastatic disease in > or =1 sentinel lymph node. Nonsurgical treatment was
      modified in 38% of patients because of sentinel lymph node biopsy results.
      Changes included adjuvant chemotherapy and/or hormonal therapy, adjuvant axillary
      radiotherapy, and decisions against adjuvant therapy. CONCLUSIONS: These data
      suggest that sentinel lymph node biopsy in elderly breast cancer patients is
      beneficial.

PMID- 15474446
TI  - Outcomes of sonography-based management of breast cysts.
AB  - BACKGROUND: Ultrasound is commonly used during diagnosis of breast lesions. Our
      purpose was to study the role of sonography for risk stratification of malignancy
      in the diagnosis and management of palpable breast cysts. METHODS: This was a
      cohort study of 176 patients with palpable breast cysts. Sonographic findings
      were correlated with clinical and pathologic outcomes. RESULTS: Mean cyst size
      was 2.0 +/- 1.8 cm. Cysts were simple, complex and probably benign, and complex
      and suspicious for neoplasm in 82.25%, 10.25% and 7.5% of patients, respectively.
      Thick cyst wall (P = 0.0001), mural tumor (P <0.00001), eccentric mass (P =
      0.034), and internal septae (P = 0.031) were predictive of neoplasm. Of cysts >3
      cm, 33% were cancerous (P = 0.000027). After 378 days of follow-up, 26 % of cysts
      had recurred. Recurrence was more frequent in patients with bilateral or multiple
      cysts (P = 0.004). CONCLUSIONS: Sonography is useful in risk stratification of
      malignancy in breast cysts. There is a high risk of recurrence after cyst
      aspiration.

PMID- 15474447
TI  - Personal health behaviors in women who have undergone risk-reducing mastectomy.
AB  - BACKGROUND: Risk-reducing mastectomy (RRM) remains an effective yet controversial
      modality for the primary prevention of breast cancer. Is the choice of RRM
      consistent with a generally proactive healthy lifestyle? METHODS: The National
      Prophylactic Mastectomy Registry is a volunteer database comprised of 460 women
      who have undergone bilateral RRM. Each patient received a questionnaire drawn
      from the Centers for Disease Control Behavioral Risk Factor Surveillance System.
      Their responses were compared with gender-specific national data from the Centers
      for Disease Control. RESULTS: Women in the RRM group were statistically more
      likely to engage in risk-reducing personal health behavior including not smoking,
      exercising, maintaining their health, and taking advantage of screening programs.
      CONCLUSIONS: Women in the registry who underwent RRM practiced a more "healthy"
      lifestyle than gender-matched controls. Therefore, the decision to have
      prophylactic surgery may have been part of a proactive approach toward their
      overall physical well-being.

PMID- 15474449
TI  - Bloodless partial splenectomy.

PMID- 15474450
TI  - Bloodless partial splenectomy.

PMID- 15474451
TI  - In search of new structural states of exchangeable apolipoproteins.
AB  - Based upon state of the art biophysical experimentation, this article focuses on
      the different structural arrangements exchangeable apolipoproteins achieve when
      placed on Langmuir monolayers and subjected to changes in lateral pressure. We
      have studied the monolayers of apolipoproteins CI, CIII, AI, AII, and E that show
      as secondary structure a high percentage of amphipathic alpha-helix. This has
      been achieved employing techniques such as Brewster angle microscopy, synchrotron
      X-ray diffraction, and surface pressure measurements. In addition, the lateral
      order of protein arrays has been also studied by atomic force microscopy. These
      monolayers show that a phase transition from a two-dimensional disorder fluid to
      an ordered state is detected at relatively high lateral pressure, where unusual
      one-dimensional solid phases are discovered. While several helices that conform
      the apolipoprotein are confined to the interface, others are uniformly tilted
      toward the hydrophobic air or the phospholipid fatty acid chains. Our results
      suggest that a similar ordering might also occur when these apolipoproteins are
      attached to a lipoprotein particle such as a high density lipoprotein (HDL)
      particle. Therefore, changes from a nascent or discoidal HDL to a mature
      spherical HDL might in parallel involve structural changes as those described in
      our Langmuir interfaces. Current experimentation is being carried out in order to
      elucidate if the structural states already found are related to the efficiency of
      lipid transfer between lipoprotein particles or lipoproteins and the plasma
      membrane of cells, as well as receptor ligand recognition.

PMID- 15474452
TI  - SU5416 inhibited VEGF and HIF-1alpha expression through the PI3K/AKT/p70S6K1
      signaling pathway.
AB  - Ovarian cancer has the highest mortality rate of any gynecological disease
      affecting women in Western countries. VEGF is a crucial inducer of angiogenesis
      both in vivo and in vitro. VEGF is commonly upregulated in ovarian cancer and is
      regulated by HIF-1. SU5416 is known to inhibit various stages of tumor growth. In
      this study, we show that SU5416 inhibited VEGF mRNA expression in ovarian cancer
      cells in a dose-dependent manner. SU5416 inhibited VEGF expression at the
      transcriptional level through the HIF-1 DNA binding site. HIF-1 is composed of
      HIF-1alpha and HIF-1beta subunits. SU5416 specifically decreased HIF-1alpha, but
      not HIF-1beta protein levels. To understand the signaling pathways regulating
      SU5416-inhibited VEGF and HIF-1alpha expression, we found that SU5416 inhibited
      PI3K activity. AKT is a downstream target of PI3K. We found that SU5416 also
      inhibited AKT and p70S6K1 activation and activity in a dose-dependent manner.
      These results demonstrate that SU5416 inhibited VEGF and HIF-1alpha expression
      through the inhibition of PI3K/AKT/p70S6K1 pathway in ovarian cancer cells. These
      results indicate that SU5416 may be an effective agent for ovarian cancer
      treatment through the inhibition of VEGF and HIF-1 expression, and the activation
      of PI3K/AKT/p70S6K1 signaling pathway.

PMID- 15474453
TI  - Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte
      like cells.
AB  - Bone marrow mesenchymal stem cells have been shown to transdifferentiate into
      cardiomyocytes after 5-azacytidine treatment or co-culturing with rodent
      cardiomyocytes. We investigate if adult human bone marrow stem cells can be
      differentiated ex vivo into cardiomyocyte-like cells (CLCs) independent of
      cytotoxic agents or co-culturing technique. Sternal bone marrow was collected
      from 16 patients undergoing coronary artery bypass surgery. Mesenchymal stem
      cells were differentiated in a cardiomyogenic differentiation medium containing
      insulin, dexamethasone, and ascorbic acid. Differentiation towards CLCs was
      determined by induced expression of cardiomyocyte-specific proteins.
      Differentiated CLCs expressed multiple structural and contractile proteins that
      are associated with cardiomyocytes. Thin filament associated myofibrillar
      proteins were detected early in the cells, with cardiac troponin I, sarcomeric
      tropomyosin, and cardiac titin among the first expressed. Some CLCs were found to
      develop into a nascent cardiomyocyte phenotype with cross-striated myofibrils
      characterized by alpha-actinin-positive Z bands after 4-5 passages in
      differentiated culture. These lineage-defined CLCs may be potentially useful for
      repairing damaged myocardium.

PMID- 15474454
TI  - Modulation of repulsive forces between neurofilaments by sidearm phosphorylation.
AB  - Recent studies have advanced the notion that the axonal organization of
      neurofilaments (NFs) is based on mutual steric repulsion between the unstructured
      "sidearm" domains of adjacent NFs. Here, we present experimental evidence that
      these repulsive forces are modulated by the degree of sidearm phosphorylation.
      When NFs are sedimented into a gelatinous pellet, pellet volume falls with
      increasing ionic strength and enzymatic dephosphorylation; sedimentation of
      phosphorylated NFs in the presence of divalent cations also dramatically reduces
      pellet volume. Further, atomic force microscopy imaging of isolated mammalian NFs
      reveals robust exclusion of colloidal particles from the NF backbone that is
      reduced at high ionic strength and attenuated when the filaments are
      enzymatically dephosphorylated. Phosphate-phosphate repulsion on the NF sidearm
      appears to modulate NF excluded volume in a graded fashion, thereby controlling
      axonal NF organization through interfilament forces.

PMID- 15474455
TI  - E2F6: a member of the E2F family that does not modulate squamous differentiation.
AB  - The inhibition of E2F has been demonstrated to be important in the initiation of
      squamous differentiation by two independent manners: promotion of growth arrest
      and the relief of the differentiation-suppressive properties of E2Fs. E2F6 is
      reported to behave as a transcriptional repressor of the E2F family. In this
      study, we examined the ability of E2F6 to act as the molecular switch required
      for E2F inhibition in order for keratinocytes to enter a terminal differentiation
      programme. Results demonstrated that whilst E2F6 was able to suppress E2F
      activity in proliferating keratinocytes, it did not modulate squamous
      differentiation in a differentiated keratinocyte. Furthermore, inhibition of E2F,
      by overexpressing E2F6, was not sufficient to sensitise either proliferating
      keratinocytes or the squamous cell carcinoma cell line, KJD-1/SV40, to
      differentiation-inducing agents. Significantly, although E2F6 could suppress E2F
      activity in proliferating cells, it could not inhibit proliferation of KJD-1/SV40
      cells. These results demonstrate that E2F6 does not contain the domains required
      for modulation of squamous differentiation and imply isoform-specific functions
      for individual E2F family members.

PMID- 15474456
TI  - Integrating molecular detection and response to create self-signalling
      antibodies.
AB  - Monoclonal antibodies are reproducible, specific, and cost-effective molecular
      probes; use outside the laboratory is, however, restricted by technical
      limitations. Addressing these constraints, the first self-signalling antibodies
      are now described, where specific antigen binding causes release of bound
      reporter from bispecific antibodies (BsAb) to generate a detectable signal. The
      report examines the concept that two different antibody binding sites in close
      proximity can promote interaction between molecules recognised by these sites,
      generating a signal by molecular crowding. Signal strength is found to increase
      with increasing homogeneity for a BsAb reactive with multimeric surfactant
      antigen; signal response is linear for a BsAb reactive with univalent small
      analyte deoxypyridinoline. Self-signalling is consistent with intramolecular
      steric hindrance. This is the first report detailing integration of two different
      functions, molecular detection and signal response, into BsAbs and with detection
      of large and small analytes, has generic application to antibody-based systems.

PMID- 15474457
TI  - Hsp70 release from peripheral blood mononuclear cells.
AB  - There are an increasing number of studies reporting the presence of Hsps in human
      serum. We have investigated the release of Hsp70 into blood and culture medium
      from peripheral blood mononuclear cells (PBMCs), and whether this release is due
      to cell damage or active secretion from the cells. Intact Hsp70 was released from
      cells within whole blood and from purified PBMCs under normal culture conditions.
      Hsp70 release was rapid (0.1 ng/10(6) cells/h) over the first 2 h of culture and
      continued at a reduced rate up to 24 h (<0.025 ng/10(6) cells/h). Using viable
      cell counts and lactate dehydrogenase release we were able to confirm that the
      release of Hsp70 was not due to cellular damage. Hsp70 release was inhibited by
      monensin, methyl-beta-cyclodextrin, and methylamine, but not by brefeldin A.
      These data suggest that Hsp70 is released from cells via a non-classical pathway,
      possibly involving lysosomal lipid rafts.

PMID- 15474458
TI  - STAT3 induces anti-hepatitis C viral activity in liver cells.
AB  - Hepatitis C virus (HCV) infection is a leading cause a of chronic liver disease
      worldwide. The main therapeutic regimen is the combination of interferon alpha
      (IFN) and the nucleoside analog, Ribavirin. IFN initiates an intracellular
      antiviral state by the JAK-STAT signaling pathway, including a presumed role for
      STAT1 and STAT2. We have previously shown that the STAT3 activation occurs during
      IFN treatment of human hepatoma cells, suggesting that the STAT3-mediated pathway
      is relevant to IFN-induced antiviral activity. In this study, we investigate the
      role of activated STAT3 in the induction of anti-HCV activity in human hepatoma
      cells. We demonstrate that the STAT3 activation is involved in efficient IFN
      induced anti-HCV activity. Using an inducible, cytokine-independent, STAT3
      activation system, in which the entire coding region of STAT3 is fused with the
      ligand-binding domain of the estrogen receptor, we demonstrate that: activated
      STAT3 is tightly regulated in a stably transfected cell line by an estrogen
      analog, 4-HT; activated STAT3 initiates efficient anti-HCV activity in a HCV
      subgenomic replicon cell line; and activation of STAT3 is associated with the
      induction of a potential antiviral gene, 1-8U. In addition, we show that the
      cytokine IL-6, a potent STAT3 activator, inhibits HCV subgenomic RNA replication
      through STAT3 activation and ERK pathway. These results strongly suggest that
      STAT3 activation is capable of initiating intracellular antiviral pathways.

PMID- 15474459
TI  - Ni2+ binds to active site of hen egg-white lysozyme and quenches fluorescence of
      Trp62 and Trp108.
AB  - We found that the maximum emission of the tryptophyl fluorescence of hen egg
      white lysozyme is shifted from 337 to 323 nm and quenched to the extent of 55%
      with an increase in concentrations of NiCl2 from 0 to 2M in 50 mM Na acetate
      buffer (pH 4.7). In contrast, NaCl does not influence the fluorescence of
      lysozyme up to 2M. To elucidate the particular effects of Ni2+ on the tryptophyl
      fluorescence of lysozyme, we have measured the assembly behavior and secondary
      structure of lysozyme in various concentrations of NiCl2, and determined the
      structures of lysozyme crystals grown in 0.3, 0.5, and 1.0M NiCl2, respectively.
      The results of analytical centrifugation and circular dichroism experiments show
      that lysozyme keeps a monomer state and has an identical secondary structure,
      irrespective of NiCl2 concentrations. The crystal structures show that all
      crystals grown in different concentrations of NiCl2 have an identical main chain
      and side chain conformation. And one Ni2+ binding with Odelta atom of Asp52 in
      the active site and coordinating with five water molecules to form hexagonal
      coordination has been determined for each crystal structure. Based on these
      results, we have proposed that Ni2+ quenches the fluorescence of Trp62 and Trp108
      due to the binding of Ni2+ to the active site of lysozyme.

PMID- 15474460
TI  - Human bronchial epithelial cells express and secrete MMP-12.
AB  - Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins, which may
      be responsible for enlargement of alveoli in chronic obstructive pulmonary
      disease (COPD) and remodeling of pulmonary tissue associated with chronic asthma.
      Here, we provide novel evidence that MMP-12 is expressed and secreted by normal
      human bronchial epithelial cell cultures (NHBECs) and reveal the regulation of
      MMP-12 gene expression by tumor necrosis factor-alpha (TNF-alpha), epidermal
      growth factor (EGF), and interferon gamma (IFN-gamma). Reverse transcription
      polymerase chain reaction analyses demonstrated MMP-12 mRNA presence in
      unstimulated differentiated NHBEC cultures. Cultures stimulated independently
      with EGF or IFN-gamma failed to alter MMP-12 mRNA abundance, while TNF-alpha, TNF
      alpha+EGF, or TNF-alpha+IFN-gamma elicited relatively early (6 h) peak increases
      in MMP-12 mRNA levels. Western blot analyses specifically indicated the presence
      of MMP-12 in differentiated NHBEC-conditioned media. These findings indicate that
      the bronchial epithelium may be an important source of elastolytic activity in
      COPD and tissue remodeling in chronic asthma.

PMID- 15474461
TI  - In silico identification and structural features of six new genes similar to
      MATER specifically expressed in the oocyte.
AB  - In the present work, we have used the in silico subtraction methodology to
      identify six new mouse genes similar to NALP5/MATER, whose ESTs were represented
      almost exclusively in egg libraries. Five genes were selected for RT-PCR and/or
      in situ hybridization. These experiments confirmed their oocyte restricted
      expression. Five of these genes are localized on mouse chromosome 7, as is
      NALP5/MATER; among them, three are localized in a 300 kb cluster.

PMID- 15474462
TI  - Overexpression of CR/periphilin downregulates Cdc7 expression and induces S-phase
      arrest.
AB  - Cdc7 expression repressor (CR)/periphilin has been originally cloned as an
      interactor with periplakin, a precursor of the cornified cell envelope, and
      suggested to constitute a new type of nuclear matrix. We here show that
      CR/periphilin is a ubiquitously expressed nuclear protein with speckled
      distribution. Overexpression of CR/periphilin induces S-phase arrest. Analysis of
      expression of regulators involved in DNA replication has revealed that both mRNA
      and protein expression of Cdc7, a regulator of the initiation and continuation of
      DNA replication, are markedly downregulated by overexpression of CR/periphilin.
      However, co-expression of Cdc7 only marginally rescues S-phase arrest induced by
      CR, indicating that CR retards S-phase progression by modifying expression of
      some genes including Cdc7, which are involved in progression of DNA replication
      or coordination of DNA replication and S-phase progression.

PMID- 15474463
TI  - Effect of Add1 gene transfer on blood pressure in reciprocal congenic strains of
      Milan rats.
AB  - Genetic variants of alpha adducin (ADD1) taken alone or in interaction with those
      of beta (ADD2) and gamma (ADD3) subunits have been associated with primary
      hypertension in humans and in Milan hypertensive (MHS) rats. In this study, we
      report the dissection of the individual contribution of each rat Add gene to
      blood pressure, by congenic substitution mapping. Congenic strains were developed
      by introgressing Add1, Add2, and Add3 genes (and chr14, chr4, and chr1 associated
      segments) of MHS in the Milan normotensive rat (MNS) genetic background (MNS.H
      Add1, MNS.H-Add2, and MNS.H-Add3) and vice versa (MHS.N-Add1, MHS.N-Add2, and
      MHS.N-Add3). Systolic blood pressure (SBP) of MNS.H-Add1 rats was significantly
      higher (+10 mmHg) than that of MNS, whereas SBP of MHS.N-Add1 was significantly
      lower (-10 mmHg) than that of MHS. The differences account for 43% of the blood
      pressure differences between MHS and MNS. In contrast, SBPs of Add2 and Add3
      congenic strains were not different from those of the correspondent recipient
      parental strain. The fine mapping of chr14 congenic segment supports the identity
      of blood pressure QTL with Add1 gene.

PMID- 15474464
TI  - Molecular cloning, characterization, and expression in brain and gonad of Dmrt5
      of zebrafish.
AB  - The DM domain gene family has at least eight members with conserved DNA-binding
      DM domain, which encodes putative transcription factors related to the sexual
      regulator Dsx of Drosophila and Mab-3 of Caenorhabditis elegans. Although some of
      the DM genes are involved in sexual development, the function of most of these
      genes remains unclear. There is also few structural and functional analysis
      concerning DM domain genes of the model fish, zebrafish. We report here molecular
      cloning, sequence, and expression of zebrafish Dmrt5, which consists of two
      exons, and encodes a 440-amino acid protein with conserved DMA and DMB domains in
      addition to DM domain. Phylogenetic analysis shows that zebrafish Dmrt5 fits
      within the Dmrt5 clade of fish and mammals. Zebrafish Dmrt5 was expressed in
      early gastrula period, subsequently increased to a high level in late stage of
      gastrula period (bud stage) and lower until the hatch period. In situ
      hybridization analysis showed its expression in developing central nervous system
      of embryos, especially in mid-brain and mid-hind brain boundary. In adult, its
      expression was restricted in brain and developing germ cells, especially in
      spermatogonia, spermatocytes, spermatids, and sperm cells, and in developing
      oocytes, including early perinucleolus stage oocyte, late yolk vesicle stage
      oocyte, and oil drop stage oocyte. These data suggest that zebrafish Dmrt5 have
      potentially important roles in gonadal development and may have contributed to
      the functional endocrine axis.

PMID- 15474465
TI  - Clitocypin, a new cysteine proteinase inhibitor, is monomeric: impact on the
      mechanism of folding.
AB  - The molecular mass of clitocypin, a new type of cysteine proteinase inhibitor
      from the mushroom Clitocybe nebularis, has been determined by analytical
      ultracentrifugation and gel exclusion chromatography. The result is in agreement
      with the formula mass of 16.8 kDa, demonstrating that the inhibitor is a monomer
      in aqueous solution. This enables the kinetics of unfolding and refolding to be
      interpreted in terms of folding in a kinetically two state, highly cooperative
      transition from the thermally unfolded state.

PMID- 15474466
TI  - A novel auto-cleavage assay for studying mutational effects on the active site of
      severe acute respiratory syndrome coronavirus 3C-like protease.
AB  - The 3C-like protease (3CLpro) of severe acute respiratory syndrome (SARS) has
      been proposed as an attractive target for drug design. His41 and Cys145 were
      essential for the active site as the principal catalytic residues. In this study,
      we mutated the two sites, expressed four resulting mutants in Escherichia coli
      and characterized. All mutants showed undetectable activity in trans-cleavage
      assay. In addition, we introduced a 31-mer peptide containing an auto-cleavage
      site to the N-terminal of the proteases and found the peptide could be cleaved
      efficiently by 3CLsc itself, but, among the four mutants, only the mutant Cys145-
      >Ser showed residual activity as detected by the auto-cleavage assay. The data
      supported the proposition unequivocally that SARS-CoV 3CLpro was a member of
      serine proteases involving His41 and Cys145 residues at the active site. The auto
      cleavage assay also provided a sensitive and reliable compensation to the
      traditional trans-cleavage assay.

PMID- 15474467
TI  - Genetic polymorphisms of glutathione S-transferases M1 and T1 modulate
      hematological changes of individuals chronically exposed to natural sour gas.
AB  - In order to find the effect of genetic polymorphisms of glutathione S-transferase
      M1 (GSTM1) and GSTT1 on hematological changes of individuals chronically exposed
      to natural sour gas, the present study was done. Study subjects (59 males, 55
      females) were residents of contaminated areas of Masjid-i-Sulaiman (southwest of
      Iran). The GSTM1 and GSTT1 genotypes were determined using a polymerase chain
      reaction-based method. The multiple linear regression method was applied. There
      is significant association between GSTs genotypes and either hemoglobin (t=2.185,
      P=0.031) or hematocrit (t=2.454, P=0.016). Also there is weak association between
      GSTs genotypes and WBC counts (t=1.802, P=0.074). The hemoglobin and hematocrit
      levels and WBC counts increased in individuals who had null genotypes of GSTM1
      and GSTT1 compared to subjects with one or two active genes. Also the levels of
      hemoglobin and hematocrit and WBC counts increased in persons with one active
      genotype compared to subjects who had two active genes. There is no significant
      association between neither platelet nor WBC differential parameters and GSTs
      genotypes.

PMID- 15474468
TI  - Effect of Rubia cordifolia, Fagonia cretica linn, and Tinospora cordifolia on
      free radical generation and lipid peroxidation during oxygen-glucose deprivation
      in rat hippocampal slices.
AB  - The major damaging factor during and after the ischemic/hypoxic insult is the
      generation of free radicals, which leads to apoptosis, necrosis, and ultimately
      cell death. Rubia cordifolia (RC), Fagonia cretica linn (FC), and Tinospora
      cordifolia (TC) have been reported to contain a wide variety of antioxidants and
      have been in use in the eastern system of medicine for various disorders.
      Hippocampal slices were subjected to oxygen-glucose deprivation (OGD) and divided
      into three groups, control, OGD, and OGD+drug treated. Cytosolic reduced
      glutathione (GSH), nitric oxide [NO, measured as nitrite (NO2)]. EPR was used to
      establish the antioxidant effect of RC, FC, and TC with respect to superoxide
      anion (O*2-), hydroxyl radicals (*OH), nitric oxide (NO) radical, and
      peroxynitrite anion (ONOO-) generated from pyrogallol, menadione, DETA-NO, and
      Sin-1, respectively. RT-PCR was performed for the three herbs to assess their
      effect on the expression of gamma-glutamylcysteine ligase (GCLC), iNOS, and GAPDH
      gene expression. All the three herbs were effective in elevating the GSH levels
      and expression of the GCLC. The herbs also exhibited strong free radical
      scavenging properties against reactive oxygen and nitrogen species as revealed by
      electron paramagnetic resonance spectroscopy, diminishing the expression of iNOS
      gene. RC, FC, and TC therefore attenuate oxidative stress mediated cell injury
      during OGD and exert the above effects at both the cytosolic as well as at gene
      expression levels and may be effective therapeutic tool against ischemic brain
      damage.

PMID- 15474469
TI  - Steroid degradation gene cluster of Comamonas testosteroni consisting of 18
      putative genes from meta-cleavage enzyme gene tesB to regulator gene tesR.
AB  - Steroid degradation genes of Comamonas testosteroni TA441 are encoded in at least
      two gene clusters: one containing the meta-cleavage enzyme gene tesB and ORF1, 2,
      3; and another consisting of ORF18, 17, tesI, H, A2, and tesA1, D, E, F, G (tesA2
      to ORF18 and tesA1 to tesG are encoded in opposite directions). Analysis of
      transposon mutants with low steroid degradation revealed 13 ORFs and a gene
      (ORF4, 5, 21, 22, 23, 25, 26, 27, 28, 30, 31, 32, 33, and tesR) involved in
      steroid degradation in the downstream region of ORF3. TesR, which is almost
      identical to that of TeiR, a positive regulator of Delta1-dehydrogenase
      (corresponds to TesH in TA441) and 3alpha-dehydrogenase (currently not identified
      in TA441), in C. testosteroni ATCC11996 (Pruneda-Paz, 2004), was shown to be
      necessary for induction of the steroid degradation gene clusters identified in
      TA441, tesB to tesR, tesA1 to tesG, and tesA2 to ORF18. At least some of the ORFs
      from ORF3 to ORF33 were suggested to be involved in 9,17-dioxo-1,2,3,4,10,19
      hexanorandrostan-5-oic acid degradation.

PMID- 15474470
TI  - Zinc coupling potentiates anti-HIV-1 activity of baicalin.
AB  - Baicalin (BA) has been shown with anti-HIV-1 activity. Zinc is a nutrient
      element. The anti-HIV-1 activity of zinc complex of baicalin (BA-Zn) in vitro was
      studied and compared with the anti-HIV-1 activities between BA and BA-Zn in the
      present study. Our results suggested that BA-Zn has lower cytotoxicity and higher
      anti-HIV-1 activity compared with those of BA in vitro. The CC50s of BA-Zn and BA
      were 221.52 and 101.73 microM, respectively. The cytotoxicity of BA-Zn was about
      1.2-fold lower than that of BA. The BA and BA-Zn inhibited HIV-1 induced
      syncytium formation, HIV-1 p24 antigen and HIV-1 RT production. The EC50s of BA
      Zn on inhibiting HIV-1 induced syncytium formation (29.08 microM) and RT
      production (31.17 microM) were lower than those of BA (43.27 and 47.34 microM,
      respectively). BA-Zn was more effective than BA in inhibiting the activities of
      recombinant RT and HIV-1 entry into host cells. Zinc coupling enhanced the anti
      HIV-1 activity of baicalin.

PMID- 15474471
TI  - Reversible and nonoxidative gamma-resorcylic acid decarboxylase: characterization
      and gene cloning of a novel enzyme catalyzing carboxylation of resorcinol, 1,3
      dihydroxybenzene, from Rhizobium radiobacter.
AB  - We found a gamma-resorcylic acid (gamma-RA, 2,6-dihydroxybenzoic acid)
      decarboxylase, as a novel enzyme applicable to carboxylation of resorcinol (RE,
      1,3-dihydroxybenzene) to form gamma-RA, in a bacterial strain Rhizobium
      radiobacter WU-0108 isolated through the screening of gamma-RA degrading
      microorganisms. The activities for carboxylation of RE and decarboxylation of
      gamma-RA were detected in the cell-free extracts of R. radiobacter WU-0108 grown
      aerobically with gamma-RA. The enzyme, gamma-RA decarboxylase, was purified to
      homogeneity on SDS-PAGE through the steps of one ion-exchange chromatography and
      two kinds of hydrophobic chromatography. The molecular weight of the enzyme was
      estimated to be 130 kDa by gel-filtration, and that of the subunit was determined
      to be 34 kDa by SDS-PAGE, suggesting that the enzyme is a homotetrameric
      structure. The enzyme catalyzed the decarboxylation of gamma-RA, but not alpha-RA
      or beta-RA. Without addition of any cofactors, the enzyme catalyzed the regio
      selective carboxylation of RE to form gamma-RA, without formation of alpha-RA and
      beta-RA, and of catechol to 2,3-dihydroxybenzoic acid. In the presence of oxygen,
      this gamma-RA decarboxylase showed no decrease in both of the activities as for
      decarboxylation of gamma-RA and carboxylation of RE, different from other
      decarboxylases reported so far. The gene, rdc, encoding the gamma-RA
      decarboxylase was cloned into Escherichia coli, sequenced, and subjected to over
      expression. The deduced amino acid sequence of the rdc gene consists of 327 amino
      acid residues corresponding to 34 kDa protein, and shows 42% and 30% identity to
      those of a 2,3-dihydroxybenzoic acid decarboxylase from Aspergillus niger and a 5
      carboxyvanillate decarboxylase from Sphingomonas paucimobilis SYK-6. A site
      directed mutagenesis study revealed the two histidine residues at positions of
      164 and 218 in Rdc to be essential for the catalytic activities of
      decarboxylation of gamma-RA and carboxylation of RE.

PMID- 15474472
TI  - R(+)-methanandamide-induced cyclooxygenase-2 expression in H4 human neuroglioma
      cells: possible involvement of membrane lipid rafts.
AB  - Cannabinoids induce the expression of the cyclooxygenase-2 (COX-2) isoenzyme in
      H4 human neuroglioma cells via a pathway independent of cannabinoid- or vanilloid
      receptor activation. The underlying mechanism was recently shown to involve
      increased synthesis of ceramide, which in turn leads to activation of p38 and
      p42/44 mitogen-activated protein kinases (MAPKs). The present study investigates
      a possible contribution of membrane lipid rafts to cannabinoid-induced COX-2
      expression. To address this issue, we tested the influence of methyl-beta
      cyclodextrin (MCD), a membrane cholesterol depletor, on COX-2 expression by the
      endocannabinoid analogue R(+)-methanandamide (R(+)-MA). Incubation of H4 cells
      with MCD was associated with a loss of lipid raft integrity and a substantial
      inhibition of R(+)-MA-induced COX-2 expression and subsequent formation of
      prostaglandin E2. Moreover, MCD was shown to suppress signal transduction steps
      upstream to COX-2 induction by R(+)-MA. Accordingly, the cholesterol depletor
      suppressed R(+)-MA-induced formation of ceramide as well as phosphorylation of
      p38 and p42/44 MAPKs. Together, our results suggest that R(+)-MA induces COX-2
      expression in human neuroglioma cells via a pathway linked to lipid raft
      microdomains.

PMID- 15474473
TI  - The roles of amino acid residues at positions 43 and 45 in microsomal contents
      and enzymatic functions of rat CYP2D1 and CYP2D2.
AB  - The effects of the substitution of amino acid residues at positions 43 and 45 of
      rat CYP2D1 and CYP2D2 on their microsomal contents and enzymatic functions were
      examined. The substitution of Val-45 of CYP2D1 by glycine decreased the
      microsomal content, whereas the substitution of Gly-45 of CYP2D2 by valine
      increased. The substitution of Leu-43 of CYP2D2 by tryptophan also increased the
      microsomal protein content. In reduced CO-difference spectra, CYP2D2 showed a
      P420 peak as well as a P450 peak, whereas CYP2D1 gave only a P450 peak. The
      substitution of Leu-43 and Gly-45 of CYP2D2 by valine and tryptophan,
      respectively, markedly decreased the P420 peak in parallel with an increase in
      P450 content. These substitutions did not cause remarkable changes in drug
      oxidation capacities (bufuralol 1''-hydroxylation and debrisoquine 4
      hydroxylation) of the recombinant enzymes in terms of nmol/min/nmol CYP. The
      results indicate that amino acid residues at positions 43 and 45 are important
      for anchoring of the rat CYP2D proteins and their stabilities in the endoplasmic
      reticulum membrane.

PMID- 15474474
TI  - Characterization of an RNA bulge structure by Fourier transform infrared
      spectroscopy.
AB  - There may be several advantages associated with an antisense oligonucleotide that
      induces a bulged structure into its RNA target molecule. Many structures of RNA
      bulges are elucidated from single-stranded RNA models. However, a two-component
      system is the minimum requirement for a realistic antisense model. We have used
      Fourier transform infrared spectroscopy to investigate a single-stranded RNA
      oligonucleotide with known NMR solution structure, constructed to model a five
      nucleotide bulge, and its two-component oligonucleotide counterpart. The infrared
      spectra show A-helical base-paired stems and non-base-paired loops in both
      systems. The nucleosides are mainly in an anti-conformation. Both N-type and S
      type of sugar puckers can be inferred from the infrared region sensitive to sugar
      conformations. The S-type of sugar pucker is likely to be associated with the
      nucleotides in the bulge. The FTIR results display an overall structural
      similarity between the two model systems.

PMID- 15474475
TI  - Recruitment of C-terminal Src kinase by the leukocyte inhibitory receptor CD85j.
AB  - The CD85j inhibitory receptor (also termed ILT2 or LIR-1) is a type-I
      transmembrane protein that belongs to the Ig superfamily and is expressed by
      different leukocyte lineages. The extracellular region of CD85j binds HLA class I
      molecules and its cytoplasmic domain displays four immunoreceptor tyrosine-based
      inhibition motifs (ITIM). Upon tyrosine phosphorylation CD85j recruits the SHP-1
      tyrosine phosphatase, involved in negative signaling. In order to identify other
      molecules to which CD85j might interact with in a phosphotyrosine-dependent
      manner, a cDNA B-cell library was screened in a three-hybrid system in yeast
      using the CD85j cytoplasmic tail as bait in the presence of the Src-kinase c
      fyn420, 531Y-F, 176R-Q mutant. In this system, the C-terminal Src kinase (Csk)
      was shown to interact with CD85j. Phosphorylation-dependent recruitment of Csk to
      the CD85j cytoplasmic tail was confirmed in CD85j-transfected mammalian cells by
      immunoprecipitation and Western blot analysis. Mutational analyses and phospho
      peptide mapping suggested that the SH2 domain of Csk may preferentially bind to
      ITIM Y562 of CD85j; yet, mutation to phenylalanine of Y533, Y614, and Y644 also
      significantly reduced Csk recruitment by CD85j. Even though CD85j was detected in
      both anti-SHP1 and CSK immunoprecipitates, these two molecules did not co
      precipitate together with CD85j. Our data support the possibility that Csk
      regulates the function of CD85j.

PMID- 15474476
TI  - Proteolysis of Xenopus laevis egg envelope ZPA triggers envelope hardening.
AB  - The egg envelope of most animal eggs is modified following fertilization,
      resulting in the prevention of polyspermy and hardening of the egg envelope. In
      frogs and mammals a prominent feature of envelope modification is N-terminal
      proteolysis of the envelope glycoprotein ZPA. We have purified the ZPA protease
      from Xenopus laevis eggs and characterized it as a zinc metalloprotease.
      Proteolysis of isolated egg envelopes by the isolated protease resulted in
      envelope hardening. The N-terminal peptide fragment of ZPA remained disulfide
      bond linked to the ZPA glycoprotein moiety following proteolysis. We propose a
      mechanism for egg envelope hardening involving ZPA proteolysis by an egg
      metalloprotease as a triggering event followed by induction of global
      conformational changes in egg envelope glycoproteins.

PMID- 15474477
TI  - Runx-2 is not essential for the vitamin D-regulated expression of RANKL and
      osteoprotegerin in osteoblastic cells.
AB  - The differentiation and activity of osteoclasts are positively and negatively
      controlled by receptor activator of nuclear factor-kappaB ligand (RANKL), which
      is expressed on the surface of osteoblasts and stromal cells, and its decoy
      receptor osteoprotegerin (OPG), which is secreted by osteoblasts and stromal
      cells, respectively. The expression of the genes for RANKL and OPG is regulated
      by 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)]. Runt-related gene-2
      (Runx-2) is essential for osteoblast differentiation and there are several
      reports that Runx-2 is involved in osteoclast formation. Therefore, to clarify
      the role of Runx-2 in osteoclastogenesis, we designed a series of experiments
      using C2 cells and C6 cells, which are derived from calvariae of runx2-deficient
      mice. Treatment of C2 cells and C6 cells with 1alpha,25(OH)(2)D(3) for 2-4 days
      increased and decreased the levels of expression of the mRNAs for RANKL and OPG,
      respectively, and the effects were dose-dependent. However, by day 8, the level
      of RANKL mRNA had fallen and that of OPG mRNA had risen. Furthermore, C6 cells
      induced the differentiation of mouse spleen cells into tartrate-resistant acid
      phosphatase-positive (TRAP-positive) multinucleated cells (osteoclast-like cells)
      in the presence of 10(-7)M 1alpha,25(OH)(2)D(3). Such formation of osteoclast
      like cells was inhibited by exogenous OPG in a dose-dependent manner. Thus, our
      findings indicate that Runx-2 is not essential for the expression of RANKL and
      OPG, and the formation of osteoclast-like cells.

PMID- 15474478
TI  - Molecular models of cyclin-dependent kinase 1 complexed with inhibitors.
AB  - Roscovitine and flavopiridol have been shown to potently inhibit cyclin-dependent
      kinase 1 and 2 (CDK1 and 2). The structures of CDK2 complexed with roscovitine
      and deschoroflavopiridol have been reported, however no crystallographic
      structure is available for complexes of CDK1 with inhibitors. The present work
      describes two molecular models for the binary complexes CDK1:roscovitine and
      CDK1:flavopiridol. These structural models indicate that both inhibitors strongly
      bind to the ATP-binding pocket of CDK1 and structural comparison of the CDK
      complexes correlates the structures with differences in inhibition of these CDKs
      by flavopiridol and roscovitine. This article explains the structural basis for
      the observed differences in activity of these inhibitors.

PMID- 15474479
TI  - Differential expression of VEGF isoforms and receptors in knee joint menisci
      under systemic hypoxia.
AB  - Vascular endothelial growth factor (VEGF) gene gives rise to several distinct
      isoforms of VEGF, which differ in their expression patterns as well as their
      biochemical and biological properties. We examined the expression levels of VEGF
      isoforms and their receptors in the medial and lateral meniscus of rabbits under
      normal physiologic conditions as well their expression levels after 8 and 24 h of
      systemic normobaric hypoxia (13%). VEGF121 is the most abundant VEGF isoform in
      the medial and lateral meniscus, followed by VEGF165, VEGF189, and VEGF183. While
      the soluble VEGF121 and VEGF165 are only upregulated at 8 h of hypoxia, the
      membrane-bound VEGF183 and VEGF189 are further increased at 24 h. VEGFR-2 is
      expressed at a much higher level than VEGFR-1 under normal conditions, and both
      receptors are upregulated under hypoxia. Differential expression levels under
      normoxia as well as a differential response to hypoxia may indicate different
      functions of VEGF isoforms in the meniscus.

PMID- 15474480
TI  - The C-terminal peptide of thrombospondin-4 stimulates erythroid cell
      proliferation.
AB  - Erythropoietin (EPO) stimulates the production of small erythroid cell
      stimulating factors (molecular weight <5 kDa) in cultures of bone marrow
      endothelial cells. We identified a fragment of thrombospondin-4 (TSP-4) as an EPO
      stimulated protein in endothelial cell lysates. Pre-incubation of the low
      molecular weight fractions from supernatants of EPO-treated umbilical cord
      endothelial cells (HUVEC) with antibodies against the C-terminal residues of TSP
      1,2 and TSP-4 decreased the erythroid cell stimulating activity. The C-terminal
      TSP-1 section corresponding to a molecular weight lower than 6 kDa has the
      integrin-associated protein binding motif VVM. The corresponding TSP-4 fragment,
      lacking the three residue sequence VVM, has a distinctive acidic peptide
      comprising the last 21 amino acids (C21) with the characteristics of an
      amphipathic helix. C21 stimulated thymidine incorporation into bovine erythroid
      cells, increased cell numbers in cultures of cord blood CD36+ erythroid
      precursors and skin fibroblasts, and decreased HUVEC proliferation. SC21, a
      homologous peptide of identical amino acid composition but with interchanged
      residues, was non-amphipathic and had no erythroid cell stimulating activity.

PMID- 15474481
TI  - Molecular cloning, characterization, and overexpression of a novel [Fe]
      hydrogenase isolated from a high rate of hydrogen producing Enterobacter cloacae
      IIT-BT 08.
AB  - Degenerate primers were designed from the conserved zone of hydA structural gene
      encoding for catalytic subunit of [Fe]-hydrogenase of different hydrogen
      producing bacteria. A 750 bp of PCR product was amplified by using the above
      mentioned degenerate primers and genomic DNA of Enterobacter cloacae IIT-BT 08 as
      template. The amplified PCR product was cloned and sequenced. The sequence showed
      the presence of an ORF of 450 bp with significant similarity (40%) with C
      terminal end of the conserved zone (H-cluster) of [Fe]- hydrogenase. hydA ORF was
      then amplified and cloned in-frame with GST in pGEX4T-1 and overexpressed in a
      non-hydrogen producing Escherichia coli BL-21 to produce a GST-fusion protein of
      a calculated molecular mass of about 42.1 kDa. Recombinant protein was purified
      and specifically recognized by anti-GST monoclonal antibody through Western blot.
      Southern hybridization confirmed the presence of this gene in E. cloacae IIT-BT
      08 genome. In vitro hydrogenase assay with the overexpressed hydrogenase enzyme
      showed that it is catalytically active upon anaerobic adaptation. In vivo
      hydrogenase assay confirmed the presence of H2 gas in the gas mixture obtained
      from the batch culture of recombinant E. coli BL-21. A tentative molecular
      mechanism has been proposed about the transfer of electron from electron donor to
      H-cluster without the mediation of the F-cluster.

PMID- 15474482
TI  - Enhancement of pheromone response by RGS9 and Gbeta5 in yeast.
AB  - The G-protein gamma-subunit-like (GGL) domain present within a subfamily of RGS
      proteins binds specifically to Gbeta5. This interaction and resulting biological
      effect impacts the standard model of heterotrimeric G-protein signaling. It has
      been hypothesized that the RGS/Gbeta5 may potentially substitute for Gbetagamma
      in the heterotrimeric complex. Saccharomyces cerevisiae pheromone responsive
      mating signaling pathway is primarily driven by Gbetagamma. We evaluated GGL
      containing RGS9 and RGS7 for functional complementation in a RGS (sst2Delta)
      knockout yeast strain. The potential of Gbeta5 to augment the function of these
      RGS proteins was also evaluated. While Gbeta5 had no effect on RGS7, coexpression
      of Gbeta5 with RGS9 enhanced cell cycle arrest, suggesting that under certain
      conditions, RGS9 and Gbeta5 may possibly function as betagamma dimer.
      Furthermore, we demonstrate that Gbeta5 can complement a ste4Delta, the yeast
      beta-subunit, thus providing the first evidence of functional complementation of
      a mammalian Gbeta.

PMID- 15474483
TI  - Transcriptome and proteome expression in activated human CD4 and CD8 T
      lymphocytes.
AB  - T-lymphocytes (T-cells) are unique in that unlike monocytes, they have no insulin
      receptors, and are insulin insensitive, but upon activation with antigens develop
      insulin, IGF-1, and IL-2 receptors, and become insulin sensitive tissues. In vivo
      activation of these cells has now been demonstrated in patients with diabetic
      ketoacidosis. We analyzed the genomics and proteomics of activated and non
      activated CD4+ and CD8+ T-cells of normal subjects using Affymetrix microarray
      gene chips and proteomes by SELDI-TOF mass spectrometry analysis. Genes for IL-2,
      insulin, and IGF-1 receptors were increased at least 2-fold in activated vs non
      activated T-cells. Using an expression array containing the entire human genome
      of 39,500 genes, we evaluated approximately 27,000 genes relevant in physiologic
      and cellular ontologies. Of these, approximately 10,500 genes were increased in
      activated cells, compared to about 7,000, which were decreased, and approximately
      9500, which were unchanged. Among activated ontologies were signal transduction
      pathways such as IRS-1, IRS-2, Akt, and glycolytic pathways. To our knowledge
      this is the first report of an hitherto unreported event. Possible implications
      of these processes are discussed in the light of their physiological
      significance.

PMID- 15474484
TI  - PPARalpha ligands activate antioxidant enzymes and suppress hepatic fibrosis in
      rats.
AB  - Oxidative stress is a major pathogenetic factor in hepatic fibrosis. Peroxisome
      proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor which is
      known to affect oxidative stress and PPARalpha ligands may have rescue effects on
      hepatic fibrosis. We tested this hypothesis using rat thioacetamide (TAA) models
      of liver cirrhosis. Rats were given intraperitoneal injection of TAA and treated
      with a diet containing one of the two PPARalpha ligands, Wy-14,643 (WY) or
      fenofibrate. WY treatment dramatically reduced hepatic fibrosis and also
      prevented the inhibition catalase of mRNA expression caused by TAA.
      Correspondingly, catalase activity increased in the TAA+WY group but decreased in
      the control TAA group. The antifibrotic action of fenofibrate in the TAA model
      was comparable with that of WY. PPARalpha ligands have an antifibrotic action in
      the rat TAA model of liver cirrhosis, probably due to an antioxidant effect of
      enhanced catalase expression and activity in the liver.

PMID- 15474485
TI  - Peri/nuclear localization of intact insulin-like growth factor binding protein-2
      and a distinct carboxyl-terminal IGFBP-2 fragment in vivo.
AB  - Insulin-like growth factor binding protein-2 (IGFBP-2) as one of the most
      important IGFBPs has never been assessed in the intracellular compartment in
      vivo. Since there is evidence for novel intracellular functions of distinct
      IGFBPs, we investigated the presence of IGFBP-2 inside the cell. In peri/nuclear
      fractions of various tissues isolated from IGFBP-2 transgenic and non-transgenic
      mice we were able to show the presence of intact IGFBP-2. In addition, we
      demonstrate the presence of a highly conserved carboxyl-terminal IGFBP-2 fragment
      in the peri/nuclear fraction by using different peptide-induced antibodies. In
      pancreatic sections, confocal microscopy revealed the presence of IGFBP-2 on the
      nuclear surface but not within the nucleus. Our findings suggest novel functions
      of intact IGFBP-2 and IGFBP-2 fragments within the cell.

PMID- 15474487
TI  - Cloning and characterization of the lanosterol 14alpha-demethylase (ERG11) gene
      in Cryptococcus neoformans.
AB  - The ergosterol pathway in fungal pathogens is an attractive antimicrobial target
      because it is unique from the major sterol (cholesterol) producing pathway in
      humans. Lanosterol 14alpha-demethylase is the target for a major class of
      antifungals, the azoles. In this study we have isolated the gene for this enzyme
      from Cryptococcus neoformans. The gene, ERG11, was recovered using degenerate PCR
      with primers designed with a novel algorithm called CODEHOP. Sequence analysis of
      Erg11p identified a highly conserved region typical of the cytochrome P450 class
      of mono-oxygenases. The gene was present in single copy in the genome and mapped
      to one end of the largest chromosome. Comparison of the protein sequence to a
      number of major human fungal pathogen Erg11p homologs revealed that the C.
      neoformans protein was highly conserved, and most closely related to the Erg11p
      homologs from other basidiomycetes. Functional studies demonstrated that the gene
      could complement a Saccharomyces cerevisiae erg11 mutant, which confirmed the
      identity of the C. neoformans gene.

PMID- 15474486
TI  - Analyses to clarify rich fractions in hepatic progenitor cells from human
      umbilical cord blood and cell fusion.
AB  - Umbilical cord blood (UCB) is a source of hematopoietic stem cells and other stem
      cells, and human UCB cells have been reported to contain transplantable hepatic
      progenitor cells. However, the fractions of UCB cells in which hepatic progenitor
      cells are rich remain to be clarified. In the present study, first, the
      fractionated cells by CD34, CD38, and c-kit were transplanted via portal vein of
      NOD/SCID mice, and albumin mRNA expression was examined in livers at 1 and 3
      months posttransplantation. At 1 and 3 months, albumin mRNA expression in
      CD34+UCB cells-transplanted livers was higher than that in CD34- cells
      transplanted livers. Albumin mRNA expression in CD34+CD38+ cells-transplanted
      livers was higher than that in CD34+CD38- cells-transplanted [corrected] liver at
      1 month. However, it was much higher [corrected] in CD34+CD38- cell-transplanted
      livers at 3 months. Similar expression of albumin mRNA was obtained between
      CD34+CD38+c-kit+ cells- and CD34+CD38-c-kit- cells-transplanted livers, and
      between CD34+CD38-c-kit+ cells- and CD34+CD38-c-kit- cells-transplanted livers,
      respectively. Second, fluorescence in situ hybridization and immunohistochemistry
      were performed to examine whether UCB cells really transdifferentiated into
      hepatocytes or they only fused with mouse hepatocytes. In mouse liver sections,
      of 1.2% cells which had human chromosomes, 0.9% cells were due to cell fusion,
      whereas 0.3% cells were transdifferentiated into human hepatocytes. These results
      suggest that CD34+UCB cells are rich fractions in hepatic progenitor cells, and
      that transdifferentiation from UCB cells into hepatocytes as well as cell fusion
      simultaneously occur in this situation.

PMID- 15474488
TI  - Identification of residual structure within denatured antichymotrypsin:
      implications for serpin folding and misfolding.
AB  - The native serpin fold is metastable and possesses the inherent ability to
      convert into more stable, but inactive, conformations. In order to understand why
      serpins attain the native fold instead of other more thermodynamically favourable
      folds we have investigated the presence of residual structure within denatured
      antichymotrypsin (ACT). Through mutagenesis we created a single tryptophan
      variant of ACT in which a Trp residue (276) is situated on the H-helix, located
      within a region known as the B/C barrel. The presence of residual structure
      around Trp 276 in 5 M guanidine hydrochloride (GdnHCl) was shown by fluorescence
      and circular dichroism spectroscopy and fluorescence lifetime experiments. The
      residual structure was disrupted in the presence of 5 M guanidine thiocyanate
      (GdnSCN). Protein refolding studies showed that significant refolding could be
      achieved from the GdnHCl denatured state but not the GdnSCN denatured form. The
      implications of these data on the folding and misfolding of the serpin
      superfamily are discussed.

PMID- 15474489
TI  - Modulation of matrix metalloproteinase-9 activity by hyaluronan is dependent on
      NF-kappaB activity in lymphoma cell lines with dissimilar invasive behavior.
AB  - Expression and activity of matrix metalloproteinase-9 (MMP-9) as well as its
      relationship with hyaluronan (HA) and NF-kappaB activity were analyzed in two
      murine lymphoma cell lines with dissimilar migration and invasive behavior. MMP
      activity was evaluated by zymograms in supernatants, membrane extracts of tumor
      cells, and in the organs invaded by these cells. The more aggressive LBLa cell
      line showed MMP-9 activity in vitro, which increased after HA treatment and was
      blocked by anti-CD44 mAb. Such activity was not found in the less aggressive
      LBLc. MMP-9 and MMP-2 activity was found in organs invaded by both cell lines,
      although differential MMP-9 activity was observed in lung infiltrated only by
      LBLa cell line. NF-kappaB activation was evaluated to determine whether
      differential activity of MMP-9 was dependent on downstream signaling pathway,
      showing higher NF-kappaB activity in the more aggressive LBLa cell line. Our
      results showed that MMP-9 activity modulated by HA through NF-kappaB signaling
      pathway may be involved in the aggressive behavior of LBLa.

PMID- 15474490
TI  - Toxoplasma gondii exposes phosphatidylserine inducing a TGF-beta1 autocrine
      effect orchestrating macrophage evasion.
AB  - Toxoplasmosis is a worldwide disease caused by Toxoplasma gondii. Activated
      macrophages control T. gondii growth by nitric oxide (NO) production. However, T.
      gondii active invasion inhibits NO production, allowing parasite persistence.
      Here we show that the mechanism used by T. gondii to inhibit NO production
      persisting in activated macrophages depends on phosphatidylserine (PS) exposure.
      Masking PS with annexin-V on parasites or activated macrophages abolished NO
      production inhibition and parasite persistence. NO production inhibition depended
      on a transforming growth factor-beta1 (TGF-beta1) autocrine effect confirmed by
      the expression of Smad 2 and 3 in infected macrophages. TGF-beta1 led to
      inducible nitric oxide synthase (iNOS) degradation, actin filament (F-actin)
      depolymerization, and lack of nuclear factor-kappaB (NF-kappaB) in the nucleus.
      All these features were reverted by TGF-beta1 neutralizing antibody treatment.
      Thus, T. gondii mimics the evasion mechanism used by Leishmania amazonensis and
      also the anti-inflammatory response evoked by apoptotic cells.

PMID- 15474491
TI  - Generation and characterization of Clostridium septicum alpha toxin mutants and
      their use in diagnosing paroxysmal nocturnal hemoglobinuria.
AB  - Glycosylphosphatidylinositol (GPI) anchors various proteins to the membrane of
      eukaryotic cells. Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic
      stem cell disorder that is primarily due to the lack of GPI-anchored proteins on
      the surface of blood cells. To detect the GPI-deficient cells in PNH patients, we
      modified alpha toxin, a pore-forming toxin of the Gram-positive bacterium
      Clostridium septicum. We first showed that aerolysin, a homologous toxin from
      Aeromonas hydrophila, bound to both of Chinese hamster ovary cells deficient of N
      glycan maturation as well as GPI biosynthesis at a significant level. However,
      alpha toxin bound to the mutant cells of N-glycosylation, but not to GPI
      deficient cells. It suggested that alpha toxin could be used as a specific probe
      to differentiate only GPI-deficient cells. As a diagnostic probe, alpha toxin
      must be the least cytotoxic while maintaining its affinity for GPI. Thus, we
      constructed several mutants. Of these, the mutants carrying the Y155G or
      S189C/S238C substitutions bound to GPI as well as the wild-type toxin. These
      mutants also efficiently underwent proteolytic activation and aggregated into
      oligomers on the cell surface, which are events that precede the formation of a
      pore in the host cell membrane, leading to cell death. Nevertheless, these
      mutants almost completely failed to kill host cells. It was revealed that the
      substitutions affect the events that follow oligomerization. The S189C/S238C
      mutant toxin differentiated GPI-deficient granulocyte and PMN, but not red blood
      cells, of a PNH patient from GPI-positive cells at least as sensitively as the
      commercial monoclonal antibodies that recognize the CD59 or CD55 GPI proteins on
      blood cells. Thus, this modified bacterial toxin can be employed instead of
      costly monoclonal antibodies to diagnose PNH patients.

PMID- 15474492
TI  - Immunological, structural, and preliminary X-ray diffraction characterizations of
      the fusion core of the SARS-coronavirus spike protein.
AB  - The SARS-CoV spike protein, a glycoprotein essential for viral entry, is a
      primary target for vaccine and drug development. Two peptides denoted HR-N(SN50)
      and HR-C(SC40), corresponding to the Leu/Ile/Val-rich heptad-repeat regions from
      the N-terminal and C-terminal segments of the SARS-CoV spike S2 sequence,
      respectively, were synthesized and predicted to form trimeric assembly of hairpin
      like structures. The polyclonal antibodies produced by recombinant S2 protein
      were tested for antigenicity of the two heptad repeats. We report here the first
      crystallographic study of the SARS spike HR-N/HR-C complex. The crystal belongs
      to the triclinic space group P1 and the data-set collected to 2.98 A resolution
      showed noncrystallographic pseudo-222 and 3-fold symmetries. Based on these data,
      comparative modeling of the SARS-CoV fusion core was performed. The immunological
      and structural information presented herein may provide a more detailed
      understanding of the viral fusion mechanism as well as the development of
      effective therapy against SARS-CoV infection.

PMID- 15474493
TI  - PLP2/A4 interacts with CCR1 and stimulates migration of CCR1-expressing HOS
      cells.
AB  - Multiple CC chemokines bind to CCR1, which plays important roles in immune and
      inflammatory responses. To search for proteins involved in the CCR1 signaling
      pathway, we screened a yeast two-hybrid library using the cytoplasmic tail of
      CCR1 as the bait. One of the positive clones contained an open reading frame of
      456bp, of which the nucleotide sequence was identical to that of proteolipid
      protein 2 (PLP2), also known as protein A4. Mammalian two-hybrid and
      coimmunoprecipitation analyses demonstrated the association of PLP2/A4 with CCR1.
      Indirect immunofluorescence analysis revealed that PLP2/A4 was predominantly
      located in plasma membrane and colocalized with CCR1 in transfected human HEK293
      cells. In addition, focal staining of CCR1 appeared on the periphery of the
      membrane upon short exposure to Leukotactin-1(Lkn-1)/CCL15, a CCR1 agonist, and
      was costained with PLP2/A4 on the focal regions. PLP2/A4 mRNAs were detected in
      various cells such as U-937, HL-60, HEK293, and HOS cells. Overexpression of
      PLP2/A4 stimulated a twofold increase in the agonist-induced migration of
      HOS/CCR1 cells, implicating a functional role for PLP2/A4 in the chemotactic
      processes via CCR1.

PMID- 15474494
TI  - Receptor-binding domain of SARS-CoV spike protein induces highly potent
      neutralizing antibodies: implication for developing subunit vaccine.
AB  - The spike (S) protein of severe acute respiratory syndrome (SARS) coronavirus
      (CoV), a type I transmembrane envelope glycoprotein, consists of S1 and S2
      domains responsible for virus binding and fusion, respectively. The S1 contains a
      receptor-binding domain (RBD) that can specifically bind to angiotensin
      converting enzyme 2 (ACE2), the receptor on target cells. Here we show that a
      recombinant fusion protein (designated RBD-Fc) containing 193-amino acid RBD
      (residues 318-510) and a human IgG1 Fc fragment can induce highly potent antibody
      responses in the immunized rabbits. The antibodies recognized RBD on S1 domain
      and completely inhibited SARS-CoV infection at a serum dilution of 1:10,240.
      Rabbit antisera effectively blocked binding of S1, which contains RBD, to ACE2.
      This suggests that RBD can induce highly potent neutralizing antibody responses
      and has potential to be developed as an effective and safe subunit vaccine for
      prevention of SARS.

PMID- 15474495
TI  - Distinct roles for the SgIGSF adhesion molecule and c-kit receptor tyrosine
      kinase in the interaction between mast cells and the mesentery.
AB  - Intraperitoneal injection of bone marrow-derived mast cells (BMMCs) has
      therapeutic efficacy against acute bacterial peritonitis. For this role, BMMCs
      need to settle down the mesentery from the peritoneal cavity. Interaction between
      BMMCs and the mesentery was examined by using mast cell deficient WBB6F1(F1)-W/Wv
      [c-kit receptor tyrosine kinase (KIT) mutant], F1-Sl/Sld [KIT ligand stem cell
      factor mutant], and F1-tg/tg [a practically microphthalmia transcription factor
      (MITF)-null mutant] mice. Three parameters were measured: the number of BMMCs:
      (1) developed in the mesentery 5 weeks after intraperitoneal injection into mast
      cell deficient mice, (2) adhered to mesenteric mesothelial cells, and (3)
      transmigrated across the mesenteric mesothelial cell monolayer when coculturing
      both cells for 3 and 18 h, respectively. After intraperitoneal injection, F1-wild
      type (+/+) BMMCs developed in the mesentery of F1-W/Wv mice but not in that of F1
      Sl/Sld mice, while F1-tg/tg BMMCs did not develop, even in the mesentery of
      WBB6F1-W/Wv mice. In the coculture, WB-W/W BMMCs normally adhered to but poorly
      transmigrated across F1-+/+ mesothelial cells, and in accordance, F1-+/+ BMMCs
      normally adhered to but poorly transmigrated across F1-Sl/Sld mesothelial cells.
      F1-tg/tg BMMCs showed poor adhesion and transmigration, but both parameters were
      partially but significantly improved by ectopic expression of spermatogenic
      immunoglobulin superfamily (SgIGSF), a mast-cell adhesion molecule critically
      regulated by MITF. Since F1-tg/tg BMMCs expressed reduced levels of KIT, these
      results suggested that SgIGSF and KIT independently played a significant role in
      the transmigration. Among three parameters, development of mast cells in the
      mesentery well correlated with the transmigration. This process seemed important
      for mast cells to settle down from the peritoneal cavity to the mesentery.

PMID- 15474496
TI  - Crystallographic structure of PNP from Mycobacterium tuberculosis at 1.9A
      resolution.
AB  - Even being a bacterial purine nucleoside phosphorylase (PNP), which normally
      shows hexameric folding, the Mycobacterium tuberculosis PNP (MtPNP) resembles the
      mammalian trimeric structure. The crystal structure of the MtPNP apoenzyme was
      solved at 1.9 A resolution. The present work describes the first structure of
      MtPNP in complex with phosphate. In order to develop new insights into the
      rational drug design, conformational changes were profoundly analyzed and
      discussed. Comparisons over the binding sites were specially studied to improve
      the discussion about the selectivity of potential new drugs.

PMID- 15474497
TI  - Real-time characterization of virulence factor expression in Yersinia pestis
      using a GFP reporter system.
AB  - A real-time reporter system was developed to monitor the thermal induction of
      virulence factors in Yersinia pestis, the etiological agent of plague. The
      reporter system consists of a plasmid in Y. pestis in which the expression of
      green fluorescent protein (GFP) is under the control of the promoters for six
      virulence factors, yopE, sycE, yopK, yopT, yscN, and lcrE yopN, which are all
      components of the Type III secretion virulence mechanism of Y. pestis. Induction
      of the expression of these genes in vivo was determined by the increase in
      fluorescence intensity of GFP in real time, in 96-well format. Different basal
      levels of expression at 26 degrees C were observed for the Y. pestis promoters.
      Expressed as percentages of the level measured for the lac promoter (positive
      control), the basal expression levels before temperature shift were: yopE (15%),
      sycE (15%), yopK (13%), yopT (4%), lcrE (3.3%), and yscN (0.8%). Following the
      shift in temperature from 26 to 37 degrees C, the rates of expression of these
      genes increased with the yopE reporter showing the strongest degree of induction.
      The rates of induction of the other virulence factors after the temperature,
      expressed as percentages of yopE induction, were: yopK (57%), sycE (9%), yscN
      (3%), lcrE (3%), and yopT (2%). The thermal induction of each of these promoter
      fusions was repressed by calcium, and the ratios of the initial rates of thermal
      induction without calcium supplementation compared to the rate with calcium
      supplementation were: yopE (11-fold), yscN (7-fold), yopK (6-fold), lcrE (3
      fold), yopT (2-fold), and sycE (1-fold). This work demonstrates a novel approach
      to quantify gene induction and provides a method to rapidly determine the effects
      of external stimuli on expression of Y. pestis virulence factors in real time, in
      living cells, as a means to characterize virulence determinants.

PMID- 15474498
TI  - Phosphorylation of human vitamin D receptor serine-182 by PKA suppresses
      1,25(OH)2D3-dependent transactivation.
AB  - The human vitamin D receptor (hVDR), which is a substrate for several protein
      kinases, mediates the actions of its 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)
      ligand to regulate gene expression. To determine the site, and functional impact,
      of cAMP-dependent protein kinase (PKA)-catalyzed phosphorylation of hVDR, we
      generated a series of C-terminally truncated and point mutant receptors.
      Incubation of mutant hVDRs with PKA and [gamma-32P]ATP, in vitro, or
      overexpressing them in COS-7 kidney cells labeled with [32P]orthophosphate,
      revealed that serine-182 is the predominant residue in hVDR phosphorylated by
      PKA. An aspartate substituted mutant (S182D), incorporating a negative charge to
      mimic phosphorylation, displayed only 50% of the transactivation capacity in
      response to 1,25(OH)2D3 of either wild-type or an S182A-altered hVDR. When the
      catalytic subunit of PKA was overexpressed, a similar reduction in wild-type but
      not S182D hVDR transactivity was observed. In a mammalian two-hybrid system,
      S182D bound less avidly than wild-type or S182A hVDR to the retinoid X receptor
      (RXR) heterodimeric partner that co-mediates vitamin D responsive element
      recognition and transactivation. These data suggest that hVDR serine-182 is a
      primary site for PKA phosphorylation, an event that leads to an attenuation of
      both RXR heterodimerization and resultant transactivation of 1,25(OH)2D3 target
      genes.

PMID- 15474499
TI  - PPAR-gamma overexpression selectively suppresses insulin secretory capacity in
      isolated pancreatic islets through induction of UCP-2 protein.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) regulates several
      cellular functions, but its physiological role in pancreatic islet cells remains
      to be investigated. In this study, we confirmed the presence of PPAR-gamma in rat
      isolated islets and examined its role on insulin and glucagon secretion by using
      PPAR-gamma-overexpressed islets. PPAR-gamma overexpression significantly
      suppressed insulin secretion induced by stimulatory concentration of glucose
      (p<0.05). In addition, insulin secretion evoked by high potassium depolarization
      also was significantly decreased from PPAR-gamma-overexpressed islets (p<0.05).
      On the other hand, no significant change in glucagon release was observed after
      high potassium depolarization between PPAR-gamma-overexpressed and control
      islets. Insulin and glucagon content in islets was not statistically different
      between the two groups. In addition, the expression of uncoupling protein-2 (UCP
      2) was found to be induced in PPAR-gamma-overexpressed islets. This result
      clearly indicates that the deteriorative effect of PPAR-gamma overexpression on
      the secretory machinery is selective for pancreatic beta-cells. And it is
      possible that its site of action can be located in the energy-consuming
      exocytotic process of insulin secretory granules, and that the reduction of ATP
      production through increased UCP-2 reduces insulin exocytosis.

PMID- 15474500
TI  - Novel inhibitory effect on 5-lipoxygenase activity by the anti-asthma drug
      montelukast.
AB  - 5-Lipoxygenase is the key enzyme in the biosynthesis of leukotrienes, powerful
      lipid mediators involved in inflammation, cell-cell communication, and other
      important physiological and pathological conditions. Particularly, cysteinyl
      leukotrienes have been recognized as playing a significant role in the
      pathophysiology of asthma and potent and effective Cys-LT1 receptor antagonists
      have been developed for the treatment of this illness. Here we report that
      montelukast, a structural Cys-LT1 receptor antagonist, also exerts a substantial
      and apparently direct inhibitory effect on 5-lipoxygenase activity in vitro, at
      concentrations in the lower micromolar range, which are of potential therapeutic
      relevance. Thus, when human mast cells HMC-1 were stimulated with the Ca
      ionophore A23187 in the presence of montelukast (up to 100 microM) a substantial
      decline in 5-lipoxygenase biosynthesis was observed. Similar results were
      obtained in the rat mast cell-like RBL-1 cell model (IC50 congruent with 2.5
      microM) and in human polymorphonuclear leukocytes. Moreover, montelukast directly
      inhibited human recombinant 5-lipoxygenase. Kinetic experiments revealed that the
      inhibition was of the non-competitive type, suggesting that montelukast binds a
      yet undefined allosteric site on 5-lipoxygenase. 5-Lipoxygenase inhibition by
      montelukast appears to be highly selective since the drug had no effects on other
      enzymes of the leukotriene cascade, viz. LTC4 synthase and LTA hydrolase.

PMID- 15474501
TI  - Three GroEL homologues from Rhizobium leguminosarum have distinct in vitro
      properties.
AB  - The GroEL molecular chaperone of Escherichia coli and its cofactor GroES are
      highly conserved, and are required for the folding of many proteins. Most but not
      all bacteria express single GroEL and GroES proteins. Rhizobium leguminosarum
      strain A34 encodes three complete operons encoding homologues to GroEL and GroES.
      We have used circular dichroism and measurement of ATPase activity to compare the
      stabilities of these chaperonins after expression in and purification from E.
      coli. Significant differences in the stabilities of the proteins with respect to
      denaturant and temperature were found. The proteins also differed in their
      ability to refold denatured lactate dehydrogenase. This study, the first to
      compare the properties of three different GroEL homologues from the same
      organism, shows that despite the high degree of similarity between different
      homologues, they can display distinct properties in vitro.

PMID- 15474502
TI  - EGF-like factor epiregulin and amphiregulin expression is regulated by
      gonadotropins/cAMP in human ovarian follicular cells.
AB  - Epiregulin and amphiregulin are growth factors involved in cancer development,
      but their potential role in signaling in the gonads is still obscure. We report
      here that basal expression of these growth factors is evident in human granulosa
      cells obtained from women treated for in vitro fertilization, when examined by RT
      PCR using RNA isolated from primary cultures of ovarian granulosa cells.
      Expression of these factors was elevated concomitantly with elevation of
      progesterone production in these cells upon stimulation with luteinizing hormone
      (LH), and to a lesser extent with follicle stimulating hormone (FSH), both
      essential stimulants for ovulation and luteinization. Epiregulin and amphiregulin
      gene expression was dose- and time-dependent when measured subsequent to LH
      stimulation. Moreover, forskolin, which activates adenylate cyclase, was as
      efficient as LH in stimulating expression of these growth factors. It is
      suggested that upregulation of the epiregulin and amphiregulin expression is part
      of the signal transduction pathway which leads to ovulation and luteinization in
      the human ovary.

PMID- 15474503
TI  - Effect of pitavastatin on apolipoprotein A-I production in HepG2 cell.
AB  - There are few reports describing the mechanism of HDL-elevating action of HMG-CoA
      reductase inhibitors (statins). As it is considered that the key step of HDL
      production is the secretion of apolipoprotein A-I (apoA-I), we investigated the
      effect of statins on apoA-I synthesis and secretion by HepG2 cell to elucidate
      the mechanism of the action. Each statin induced apoA-I expression (mRNA and
      protein) dose-dependently: the rank order of the apoA-I induction pitavastatin (3
      microM)>simvastatin (10 microM)>atorvastatin (30 microM). The induction of apoA-I
      by statins disappeared with addition of mevalonate, which indicates that the
      effect is HMG-CoA reductase inhibition-dependent. Based on HMG-CoA reductase
      inhibition, pitavastatin-induced apoA-I more efficiently than simvastatin and
      atorvastatin. Further study revealed that pitavastatin increased ABCA1 mRNA in
      HMG-CoA reductase-dependent manner and that Rho and Rho kinase inhibitor (C3T and
      Y27632) increased apoA-I production in the HepG2 cells. These results suggest
      that pitavastatin efficiently increases apoA-I in the culture medium of HepG2
      cells by promoting apoA-I production through inhibition of HMG-CoA reductase and
      suppression of Rho activity and by protecting apoA-I from catabolism through
      ABCA1 induction and lipidation of apoA-I.

PMID- 15474504
TI  - Genetic and pharmacological inhibition of poly(ADP-ribose) polymerase-1
      interferes in the chlamydial life cycle.
AB  - Chlamydiaceae are intracellular bacteria responsible for a variety of infections,
      ranging from asymptomatic to very severe, in humans and animals. We have
      investigated the role of poly(ADP-ribose) polymerase-1 (PARP-1) in Chlamydophila
      abortus infection using PARP-1-/- and their littermates PARP-1+/+ mice. Infection
      was resolved more efficiently by PARP-1-/- than PARP-1+/+ mice. However, the
      inflammatory response was similar in both strains, suggesting a potential role
      for PARP-1 in the cross-talk between this microorganism and the host cells. PARP
      1-/- fibroblasts showed a 10-fold lower rate of chlamydiae production than PARP
      1+/+. Moreover, a strong inhibition of bacterial production was also observed
      after pharmacological inhibition of PARP-1 activity in McCoy cells. Likewise,
      PARP-1 inhibition induced a higher level of cell death of infected cells,
      interfering in this way with the normal bacterial cell cycle. Overall, we
      identify PARP-1 as a new molecule involved in chlamydial developmental cycle,
      although the intrinsic mechanisms deserve further studies.

PMID- 15474505
TI  - Direct detection of caspase-3 activation in single live cells by cross
      correlation analysis.
AB  - Dual color fluorescence cross-correlation spectroscopy (FCCS) provides
      information about the coincidence of spectrally well-defined two fluorescent
      molecules in a small observation area at the single-molecule level. To evaluate
      the activity of caspase-3 in vivo directly, FCCS was applied to single live
      cells. We constructed chimeric proteins that consisted of tandemly fused enhanced
      green FP (EGFP) and monomeric red FP (mRFP). In control experiments, the protease
      reaction was monitored in solution, where a decrease in cross-correlation
      amplitude was observed due to specific cleavage of the amino acid sequence
      between EGFP and mRFP. Moreover, a decrease in cross-correlation amplitude could
      be detected in a live cell, where caspase-3 activation was induced by apoptosis.
      This is the first report of FP-based in vivo cross-correlation analysis. FP-based
      FCCS may become the most versatile method for analysis of protein-protein
      interactions in live cells.

PMID- 15474506
TI  - Purification of a novel ribonuclease from dried fruiting bodies of the edible
      wild mushroom Thelephora ganbajun.
AB  - A ribonuclease, with a molecular mass of 30 kDa and a potent inhibitory activity
      toward HIV-1 reverse transcriptase (IC50=300 nM), was isolated from dried
      fruiting bodies of the edible wild mushroom Thelephora ganbajun. The ribonuclease
      exhibited a unique polyhomoribonucleotide specificity, with the highest activity
      toward poly(U), about 50% and 25% as much activity toward poly(A) and poly(C),
      respectively, and minimal activity toward poly(G). Unlike other mushroom RNases,
      the ribonuclease was adsorbed on DEAE-cellulose and Q-Sepharose, and unadsorbed
      on CM-cellulose. A temperature of 40 degrees C and a pH of 6-7 were required for
      maximal activity of the enzyme. The enzyme was characterized by an N-terminal
      sequence without any homology to known proteins.

PMID- 15474507
TI  - Histone deacetylase inhibitor, Trichostatin A, activates p21WAF1/CIP1 expression
      through downregulation of c-myc and release of the repression of c-myc from the
      promoter in human cervical cancer cells.
AB  - Histone deacetylase (HDAC) inhibitors have shown promise in clinical cancer
      therapy and to consistently induce p21WAF1/CIP1 expression in a p53-independent
      manner and via increased acetylation of the chromatin at the Sp1 sites in the
      p21WAF1/CIP1 promoter region. However, the exact mechanism by which HDAC
      inhibitors induce p21WAF1/CIP1 remains unclear. In this study, we observed that
      Trichostatin A (TSA), a HDAC inhibitor, induced strikingly p21WAF1/CIP1
      expression in human cervical cancer (HeLa) cells, and this induction correlated
      with downregulation of c-myc expression. Coincident with this observation, knock
      down of c-myc with a c-myc specific small interfering RNA dramatically induced
      expression of p21WAF1/CIP1 in these cancer cells. These data suggest that c-myc
      may play a critical role in repression of p21WAF1/CIP1 expression in HeLa cells.
      More importantly, using chromatin immunoprecipitation assay, we observed for the
      first time that c-myc bound to the endogenous p21WAF1/CIP1 promoter in untreated
      HeLa cells, but not in TSA-treated cells. Taken together, TSA induced c-myc
      downregulation and release from the endogenous p21WAF1/CIP1 promoter contributes,
      at least partially, to transcriptional activation of the p21WAF1/CIP1 in HeLa
      cells.

PMID- 15474509
TI  - BSp66 protease is widespread in the acrosomal region of sperm from several
      mammalian species.
AB  - Fertilization in mammals comprises a sequence of events leading to the fusion of
      sperm and oocyte membranes. Although proteases are known to be involved in this
      process, their role in fertilization is controversial. There is extensive work on
      the characterization of proteolytic systems, including serine proteases, which
      demonstrates that acrosomal proteases can be distinguished among the sperm of
      different mammalian species on the basis of the gelatin-hydrolyzing activity on
      SDS-PAGE by the quantity and variety of the enzymes. In this report, we
      investigated the occurrence and activity of the serine protease BSp66, previously
      characterized in bovine spermatozoa, in various mammalian sperm. A protein with a
      molecular mass of 66 kDa cross-reacted with heterologous antibodies against
      bovine BSp66 when sperm extracts of several mammalian species were analyzed by
      Western blot. In agreement, proteolytic activity corresponding to the molecular
      mass of BSp66 was detected by gelatin zymography in all the species analyzed.
      This protein was located on the acrosomal region of sperm cells by
      immunofluorescence methods. We concluded that BSp66 is widespread in mammalian
      sperm, with a conserved location in the acrosomal region.

PMID- 15474508
TI  - Association/dissociation of gonadotropin subunits involves disulfide bridge
      disruption which is influenced by carbohydrate moiety.
AB  - The association and dissociation rates of pituitary porcine luteinizing hormone
      (pLH) and equine LH (eLH) at oxidizing potential were slow and those of equine
      choriogonadotropin (eCG) were even much slower. At reducing potential mimicking
      endoplasmic reticulum condition, association of pLH subunits was observed in less
      than 5 min instead of 24 h at oxidizing potential. At neutral pH and 37 degrees
      C, DTNB and 2-nitro-5-thiocyanobenzoic acid (NTCB) were found to react with two
      cysteine residues (i.e., one S-S bridge) in pLH. The temperature dependence of
      the NTCB reaction on pLH was found to be similar to that of the dissociation of
      the hormone (Tm approximately 75 degrees C). The tight correlation between the
      reaction of two cysteines and dissociation of the subunits of pLH and eLH
      strongly suggests that transient opening of one fragile disulfide bridge is
      required for heterodimer assembly. Moreover, the absence of cysteine reaction
      with eCG indicates that its bulky carbohydrate chains exert a negative influence
      on the opening of this bridge leading to considerably diminished association
      dissociation rates of its subunits.

PMID- 15474510
TI  - Cell cycle-related signaling pathways modulated by peripheral benzodiazepine
      receptor ligands in colorectal cancer cells.
AB  - Specific ligands of the peripheral benzodiazepine receptor (PBR) have been shown
      to induce both apoptosis and G1/G0 cell cycle arrest in colorectal cancers. The
      signaling pathways leading to cell cycle arrest are still unknown. Using cDNA
      array technology, we identified signaling molecules involved in cell cycle arrest
      induced by the PBR ligands FGIN-1-27 and PK 11195. Differential gene expression
      was confirmed by semi-quantitative RT-PCR or Western blot analysis of gene
      products. The PBR ligand-mediated signaling involved the upregulation of the
      cyclin-dependent kinase inhibitors p21WAF1/CIP1 and p27Kip1, cdc16, and the cell
      cycle inhibitors gadd45 and gadd153, the downregulation of the cyclins D1 and B1,
      as well as the inactivation of ERK1/2. The p21-deficient colorectal cancer cell
      line HCT116 p21-/- was significantly less sensitive to PBR ligands than the
      parental HCT116 wild-type cells, demonstrating the functional involvement of
      p21WAF1/CIP1 in PBR ligand-mediated G1 arrest. This study thus revealed PBR
      ligand-triggered signaling pathways leading to cell cycle arrest. Moreover, we
      showed the functional implication and interaction of differentially expressed
      gene products and provided a model of signaling pathways involved in PBR ligand
      induced G1 arrest. These results form the basis for future PBR ligand-mediated
      therapeutic approaches.

PMID- 15474511
TI  - Cu,Zn superoxide dismutase increases intracellular calcium levels via a
      phospholipase C-protein kinase C pathway in SK-N-BE neuroblastoma cells.
AB  - The superoxide dismutase isoenzymes (SOD) play a key role in scavenging, O*2-
      radicals. In contrast with previous studies, recent data have shown that human
      neuroblastoma cells are able to export the cytosolic Cu,Zn superoxide dismutase
      (SOD1), thus suggesting a paracrine role exerted by this enzyme in the nervous
      system. To evaluate whether SOD1 could activate intracellular signalling
      pathways, the functional interaction between SOD1 and human neuroblastoma SK-N-BE
      cells was investigated. By analyzing the surface binding of biotinylated SOD1 on
      SK-N-BE cells and by measuring intracellular calcium concentrations and PKC
      activity, we demonstrated that SOD1 specifically interacts in a dose-dependent
      manner with the cell surface membrane of SK-N-BE. This binding was able to
      activate a PLC-PKC-dependent pathway that increased intracellular calcium
      concentrations mainly deriving from the intracellular stores. Furthermore, we
      showed that this effect was independent of SOD1 dismutase activity and was
      totally inhibited by U73122, the PLC blocker. On the whole, these data indicate
      that SOD1 carries out a neuromodulatory role affecting calcium-dependent cellular
      functions.

PMID- 15474512
TI  - Fluorescence labels as sensors for oxygen binding of arthropod hemocyanins.
AB  - The molecular basis of high cooperativity in multi-subunit proteins is still
      unknown in most cases. Oxygen binding by multi-subunit hemocyanins produces two
      intrinsic spectroscopic signals which are, however, either limited to the UV or
      are very weak. Here we demonstrate that fluorescence labels emitting in the
      visible can be used as sensors for cooperative oxygen binding of hemocyanins.
      Fluorescence resonance energy transfer to the oxygenated active sites quenches
      the emission of the labels by roughly 50% upon oxygenation of the protein. The
      labels give strong and photo-stable emission, allowing imaging of single
      hemocyanin molecules. Therefore, this study opens up a new perspective for
      investigating the molecular basis of cooperative oxygen binding at the single
      molecule level. In addition, another novel application is provided by these
      labels, i.e., the investigation of the influence of effectors by recording
      simultaneously the binding of oxygen in the visible and of effectors in the UV.

PMID- 15474513
TI  - Reduction of airway anion secretion via CFTR in sphingomyelin pathway.
AB  - The present study concerns the involvement of the ceramide produced through
      sphingomyelinase (SMase)-mediated catalysis in airway anion secretion of Calu-3
      cells. Short-circuit current (Isc) measurement revealed that isoproterenol (ISO,
      0.1 microM)-induced anion secretion was prevented by pretreatment with SMase (0.3
      U/ml, for 30 min) from the basolateral but not the apical side, although basal
      and 1-ethyl-2-benzimidazolinone (1-EBIO, a Ca2+-activated K+ channel opener)
      induced Isc were unaffected. The effects of SMase were reproduced in responses to
      forskolin (20 microM) or 8-bromo-cAMP (2 mM). C2-ceramide, a cell-permeable
      analog, also repressed the 8-bromo-cAMP-induced responses. Nystatin
      permeabilization studies confirmed that the SMase- and C2-ceramide-induced
      repressions were due to hindrance of augmentation of cystic fibrosis
      transmembrane conductance regulator (CFTR)-mediated conductance across the apical
      membrane. Further, SMase failed to influence K+ conductance across the
      basolateral membrane. These results suggest that the ceramide originating from
      basolateral sphingomyelin acts on activated CFTR from the cytosolic side,
      hindering anion secretion.

PMID- 15474514
TI  - Heterodimerization with vascular endothelial growth factor receptor-2 (VEGFR-2)
      is necessary for VEGFR-3 activity.
AB  - VEGFR-3 is essential for vascular development and maintenance of lymphatic
      vessel's integrity. Little is known about its cooperative effect with other
      receptors of the same family. Contrary to VEGFR-2, stimulation of VEGFR-3 by VEGF
      C and -D failed to enhance its phosphorylation either in HEK293T or in PAE cells.
      These ligands were unable to induce angiogenesis of PAEC expressing VEGFR-3
      alone. In the presence of VEGFR-2, VEGF-C and -D induced heterodimerization of
      VEGFR-3 with VEGFR-2. This heterodimerization was associated with enhanced VEGFR
      3 phosphorylation and subsequent cellular responses as evidenced by the formation
      of capillary-like structures in PAE cells and proliferation of primary human
      endothelial cells expressing both receptors. Taken together, these results show
      for the first time that VEGFR-3 needs to be associated to VEGFR-2 to induce
      ligand-dependent cellular responses.

PMID- 15474515
TI  - Computational development of an alpha1A-adrenoceptor model in a membrane mimic.
AB  - A number of subtypes of the alpha-adrenoceptor have been identified; however,
      knowledge of the three-dimensional structures of such membrane proteins is
      limited, and no crystal structure of an alpha-adrenoceptor is available to date.
      We have developed and analysed homology models of the alpha1A-adrenoceptor
      subtype based on the bovine rhodopsin crystal structure (1l9 h). Subsequent
      structural refinement was performed through molecular dynamics simulations using
      the Amber 7 suite of programs with a biphasic H2O/CHCl3/H2O cell utilised to
      mimic the receptor's natural membrane environment.

PMID- 15474516
TI  - Subcellullar localization of tumor-associated antigen 3H11Ag.
AB  - 3H11Ag, a tumor-associated antigen defined by the monoclonal antibody 3H11 that
      specifically recognizes cancer cells in various tumor tissues, was successfully
      cloned recently, but its function is unknown. To explore the potential roles it
      plays in tumors, we analyzed its subcellular localization in the present study.
      By expressing 3H11Ag fused with fluorescent protein in COS-7 cells, we found that
      3H11Ag localizes to both cytoplasm and nucleus, which was confirmed by
      subcellular fractionation. And sequentially extracting the nuclei of COS-7 cells
      transfected with 3H11Ag showed that it is a DNA- and nuclear matrix-associated
      protein. Moreover, by expressing a series of red fluorescent protein-tagged
      truncated forms of 3H11Ag, it was demonstrated that the 150 amino acid residues
      at its C-terminal are fully responsible for the subcellular localization. In
      addition, the results of the computational analysis of 3H11Ag were in accordance
      with those of the experimental analysis. All these data would be helpful to
      elucidate the functions of 3H11Ag.

PMID- 15474517
TI  - L-carnosine reduces telomere damage and shortening rate in cultured normal
      fibroblasts.
AB  - Telomere is the repetitive DNA sequence at the end of chromosomes, which shortens
      progressively with cell division and limits the replicative potential of normal
      human somatic cells. L-carnosine, a naturally occurring dipeptide, has been
      reported to delay the replicative senescence, and extend the lifespan of cultured
      human diploid fibroblasts. In this work, we studied the effect of carnosine on
      the telomeric DNA of cultured human fetal lung fibroblast cells. Cells
      continuously grown in 20 mM carnosine exhibited a slower telomere shortening rate
      and extended lifespan in population doublings. When kept in a long-term
      nonproliferating state, they accumulated much less damages in the telomeric DNA
      when cultured in the presence of carnosine. We suggest that the reduction in
      telomere shortening rate and damages in telomeric DNA made an important
      contribution to the life-extension effect of carnosine.

PMID- 15474518
TI  - Diallyl disulfide, a chemopreventive agent in garlic, induces multidrug
      resistance-associated protein 2 expression.
AB  - The organosulfur compounds (OSCs), present in garlic, are studied for their
      protective effect against human cancers. P-glycoprotein (P-gp) and multidrug
      resistance protein 2 (Mrp2) are two transporters involved in the defense of cells
      and in the development of multidrug resistance. Whereas OSCs increase glutathione
      S-transferase activity (GST), Mrp2 plays a role in the transport of glutathione
      (GSH)-conjugates. In this study, we have investigated the effect of two OSCs,
      diallyl disulfide (DADS) and S-allyl cysteine (SAC), on P-gp and Mrp2 expression
      in renal brush-border membranes. By Western blot analysis, our results show that
      DADS induces Mrp2 expression (by 7-fold), which correlates with the rise of GST
      activity and GSH levels. Surprisingly, a co-administration of OSC with cisplatin,
      an anticancer drug, significantly increased Mrp2 gene and protein expression (by
      30-fold), suggesting that DADS could potentiate the effects of cisplatin.
      Interestingly, SAC and cisplatin in co-treatment decreased P-gp protein
      expression and mdr1b isoform mRNA levels. In addition, modulation of the mdr1b
      isoform and Mrp2 by cisplatin was completely abolished by a glutathione
      precursor, N-acetyl cysteine. These results indicate that OSCs present in a
      garlic-rich diet might alter chemotherapeutic treatments using P-gp or Mrp2
      substrates.

PMID- 15474519
TI  - Pituitary transcription factor Prop-1 stimulates porcine follicle-stimulating
      hormone beta subunit gene expression.
AB  - Molecular cloning of the transcription factor that modulates the expression of
      porcine follicle-stimulating hormone beta subunit (FSHbeta) gene was performed by
      the yeast one-hybrid cloning system using the -852/-746 upstream region (Fd2) as
      a bait sequence. We eventually cloned a pituitary transcription factor, Prop-1,
      which has been identified as an upstream transcription factor of Pit-1 gene.
      Binding ability of Prop-1 to the bait sequence was confirmed using recombinant
      Prop-1, and the binding property was investigated by DNase I footprinting,
      revealing that Prop-1 certainly bound to the large AT-rich region throughout the
      Fd2. Co-transfection of Prop-1 expression vector together with a reporter gene
      fused with Fd2 in CHO cells demonstrated an attractive stimulation of reporter
      gene expression. Immunohistochemistry of adult porcine pituitary confirmed the
      colocalization of the Prop-1 and FSHbeta subunit. This study is the first to
      report that Prop-1 participates in the regulation of FSHbeta gene. The present
      finding will provide new insights into the development of pituitary cell lineage
      and combined pituitary hormone deficiency (CPHD), since why the defect of Prop-1
      causes CPHD including gonadotropins (FSH and LH) has yet to be clarified.

PMID- 15474520
TI  - Biochemical characterization of prostasin, a channel activating protease.
AB  - Human prostasin was recently identified as a potential regulator of epithelial
      sodium channel (ENaC) function. Through the use of positional scanning
      combinatorial substrate libraries, prostasin was shown to have a preference for
      poly-basic substrates: in position P4 preference was for arginine or lysine; in
      P3 preference was for histidine, lysine or arginine; in P2 preference was for
      basic or large hydrophobic amino acids; and in P1 preference was for arginine and
      lysine. P1', P2', and P3' displayed broad selectivity with the exception of a
      lack of activity for isoleucine, and P4' had a preference for small, unbranched,
      amino acids such as alanine and serine. A prostasin-preferred poly-basic cleavage
      site was found in the extracellular domains of the ENaC alpha- and beta-subunits,
      and may present a mechanism for prostasin activation. The absence of activity
      seen with substrates containing isoleucine in position P1' explains the inability
      of prostasin to autoactivate and suggests that prostasin proteolytic activity is
      regulated by an upstream protease. Prostasin activity was highly influenced by
      mono- and divalent metal ions which were potent inhibitors and substrate specific
      modulators of enzymatic activity. In the presence of sub-inhibitory
      concentrations of zinc, the activity of prostasin increased several-fold and its
      substrate specificity was significantly altered in favor of a strong preference
      for histidine in positions P3 or P4 of the substrate.

PMID- 15474521
TI  - A method to quantitatively detect H-ras point mutation based on
      electrochemiluminescence.
AB  - Conventional methods for point mutation detection are usually multi-stage,
      laborious, and need to use radioactive isotopes or other hazardous materials, and
      the assay results are often semi-quantitative. In this work, a protocol for
      quantitative detection of H-ras point mutation was developed.
      Electrochemiluminescence (ECL) assay was coupled with restriction endonuclease
      digestion directly from PCR products. Only the wild-type amplicon containing the
      endonuclease's recognition site can be cut off, and thus cannot be detected by
      ECL assay. Using the PCR-ECL method, 30 bladder cancer samples were analyzed for
      possible point mutation at codon 12 of H-ras oncogene. The results show that the
      detection limit for H-ras amplicon is 100 fmol and the linear range is more than
      three orders of magnitude. The point mutation was found in 14 (46.7%) out of 30
      bladder cancer samples. The experiment results demonstrate that the PCR-ECL
      method is a feasible quantitative approach for point mutation detection due to
      its safety, high sensitivity, and simplicity.

PMID- 15474522
TI  - Pathogenic human thyroglobulin peptides in HLA-DR3 transgenic mouse model of
      autoimmune thyroiditis.
AB  - To identify pathogenic epitopes on human thyroglobulin (hTg), a homodimer of
      660kDa, we have applied a computer-based algorithm to predict potential HLA-DR3
      binding peptides and have tested them in DR3-transgenic mice. Of the 39 peptides
      selected, four stimulated a proliferative response from hTg-primed cells of DR3+
      mice, but not DQ8+ mice. Of the four peptides, one, hTg2079, was consistently
      pathogenic. Thyroiditis was not only produced by adoptive transfer of hTg-primed,
      hTg2079-activated cells but also by direct immunization with the peptide. These
      results demonstrate the utility of using this computer-based algorithm with
      synthetic peptides to help identify pathogenic T cell epitopes on hTg.

PMID- 15474523
TI  - Impaired antigen-induced CD8+ T cell clonal expansion in aging is due to defects
      in antigen presenting cell function.
AB  - CD8+ T cell activation depends on interaction with antigen-presenting cells
      (APCs) and this interaction leads to the expansion of T cells with the capacity
      to control infection. Using professional APCs, we demonstrate that with age, the
      duration of APC-T cell contact time required to achieve clonal expansion
      increases. Naive CD8+ T cells from aged mice showed no defect in antigen-induced
      proliferation when stimulated with APC from young mice. In contrast, CD8+ T cells
      from young mice exhibited reduced clonal expansion and secreted significantly
      lower amounts of IFN-gamma when stimulated by APCs from aged mice. The aged APCs
      were defective in costimulatory molecule expression and cytokine and chemokine
      secretion. These data indicate that defects in APC function lead to poor T cell
      clonal expansion and function in aging.

PMID- 15474524
TI  - Polymyxin B enhances ISS-mediated immune responses across multiple species.
AB  - The immunostimulatory effects of bacterial DNA on mammalian cells have been
      localized to unmethylated CpG motifs, and synthetic CpG-containing
      oligodeoxynucleotides that mimic these effects are known as immunostimulatory
      sequences (ISS). We have found that the polycationic antibiotic, polymyxin B
      (PMXB), associates with ISS and serum albumin in vitro and forms microparticles
      that greatly increase the activity of ISS on plasmacytoid dendritic cells (PDCs).
      Specifically, ISS/PMXB greatly enhanced IFN-alpha production from PDCs and other
      activities downstream of IFN-alpha, including IFN-gamma secretion, NK lytic
      activity, and the expression of genes dependent upon IFN-alpha/IFN-gamma. This
      amplification was specific for the IFN-alpha pathway since other ISS activities,
      including B cell proliferation, B cell IL-6 secretion, and PDC maturation, were
      not affected by PMXB. Both the polycationic peptide and lipophilic fatty acid
      side chain domains of PMXB, as well as the presence of a third party stabilizing
      agent such as albumin or Tween 85, were required for particle formation and
      enhanced ISS activity. The ISS-enhancing activity of PMXB was observed across
      multiple species (human, primate, and mouse) and in vivo (primate, mouse). These
      data illustrate the usefulness of formulating ISS with a cationic lipopeptide
      such as PMXB, which focuses and greatly amplifies the ISS-induced pathway of IFN
      alpha-mediated responses.

PMID- 15474525
TI  - Regulation of antigen-specific versus by-stander IgE production after antigen
      sensitization.
AB  - IgE is critical in the pathogenesis of allergic disorders. In this report, we
      investigated the differential regulation of antigen-specific and by-stander IgE.
      Ovalbumin (OVA) immunization did not increase IgE producing cells in the spleen,
      but significantly enhanced the intracellular IgE content of all IgE+ cells. In
      contrast, OVA induced a significant increase of IgE+ cells in the draining lymph
      nodes (LN). Furthermore, OVA-specific IgE was detected only in the ex vivo
      cultures of the draining LN but not the spleen cells, while total IgE was
      increased in both cultures. These results indicated that antigen-specific IgE was
      mainly produced in the draining LN, while the spleen was a major source for by
      stander IgE. Anti-IL-4, but not anti-IL-13, antibody blocked the expansion of IgE
      producing cells in the draining LN as well as systemic OVA-specific and total IgE
      levels, indicating IL-4 was important in both antigen-specific IgE generation and
      total IgE upregulation.

PMID- 15474526
TI  - Phenotype and function of GM-CSF independent dendritic cells generated by long
      term propagation of rat bone marrow cells.
AB  - GM-CSF is believed to be an essential factor for growth and differentiation of
      myeloid dendritic cells (DC). Employing a low-density fraction of rat bone marrow
      cells, we attempted to generate DC with human Flt-3/Flk-2 and IL-6. In this
      culture system, typical DC gradually appeared without exogenous GM-CSF
      supplement. Phenotypes and functions of the DC were examined. Evidence provided
      that the most efficient long-term outgrowth of DC progenitors was obtained by GM
      CSF independent culture systems with the aid of Flt3/Flk-2 and IL-6, not with c
      kit ligand and IL-6. Furthermore, CD103 (OX-62), which is widely used for rat DC
      separation, was found to be insufficient for enriching DC, due to the down
      regulation of the marker. However, the most efficient selection of rat DC was
      made by CD161a (NKR-P1A), a C-type lectin family. The GM-CSF independent DC was
      functionally active in vitro as well as in vivo assays.

PMID- 15474528
TI  - Alcohol and HIV decrease proteasome and immunoproteasome function in macrophages:
      implications for impaired immune function during disease.
AB  - Proteasomes (proteinase complexes, PR) and immunoproteasomes (IPR) degrade
      damaged proteins and affect protein processing required for antigen presentation
      by mononuclear phagocytes. These critical immune processes are attenuated during
      progressive HIV-1 infection and are affected by alcohol abuse. To investigate the
      mechanisms underlying these functional changes, we measured PR and CYP2E1
      activities [an ethanol (EtOH) metabolizing enzyme] and reactive oxygen species
      (ROS) in human monocyte-derived macrophages (MDM) following HIV-1 infection and
      EtOH treatment. We observed progressive declines of PR activity and PR/IPR
      contents in HIV-1-infected MDM. PR activity and IPR expression increased after
      IFN-gamma stimulation but reduced after HIV-1 infection. EtOH inhibited both IFN
      gamma-induced PR and IPR. Paradoxically, EtOH attenuated PR catalytic activity in
      infected MDM and suppressed viral replication. Elevated ROS followed EtOH
      exposure and paralleled decreased PR activity. The latter was restored by anti
      oxidant. The data support the notion that HIV-1 infection and EtOH may work in
      concert to affect immune function including antigen presentation and thereby
      affect disease progression.

PMID- 15474527
TI  - Macrophages exposed to lymphotropic and monocytotropic HIV induce similar CTL
      responses despite differences in productive infection.
AB  - Macrophages are accessory cells that are vulnerable to infection by HIV-1. HTLV
      IIIB, a lymphotropic strain of HIV, infects macrophages poorly resulting in
      either no or low levels of virus expression compared to high levels of productive
      infection after exposure of macrophages to the monocytotropic HIV strain Ada-M.
      Whether this results in an impaired ability of HTLV-IIIB-exposed macrophages to
      initiate protective cytotoxic T lymphocyte (CTL) immune responses against these
      strains is not well defined. We investigated the ability of monocyte-derived
      macrophages (MDM) exposed to lymphotropic and monocytotropic HIV strains to
      initiate primary CTL responses in vitro. MDM exposed to HTLV-IIIB induced a
      specific primary CTL response that was comparable to MDM exposed to the
      monocytotropic strain Ada-M despite marked differences in productive HIV
      infection in MDM between the two strains. CTL generated in this model were MHC
      restricted, strain-specific, and CD8+. These data demonstrate that high levels of
      productive HIV infection in accessory cells are not a prerequisite for the
      generation of a primary CTL response, suggesting a novel immunologic interaction
      between MDM and lymphotropic HIV strains.

PMID- 15474529
TI  - Differential effects on innate versus adaptive immune responses by WF10.
AB  - Oxidative compounds that are physiologically generated in vivo can induce natural
      defense mechanisms to enhance the elimination of pathogens and to limit
      inflammatory tissue damage in the course of inflammation. Here, we have
      investigated WF10, a chlorite-based non-toxic compound for its functional
      activities on human PBMC in vitro. WF10 exerts potent immune-modulatory effects
      through generating endogenous oxidative compounds such as taurine chloramine.
      Proliferation and IL-2 production of anti-CD3 stimulated PBMC were inhibited by
      WF10, as was the nuclear translocation of the transcription factor NFATc. In PBMC
      and monocytes, however, WF10 induced pro-inflammatory cytokines like IL-1beta, IL
      8, and TNF-alpha. In the monocytic cell line THP-1, the activation of the
      transcription factors AP-1 and NFkappaB by WF10 was demonstrated. Inhibition of
      NFAT regulated genes in activated lymphocytes in concert with the induction of
      several myeloid cell associated pro-inflammatory genes in monocytes represents a
      novel mechanism of immune modulation.

PMID- 15474530
TI  - Evidence that 4-pregnen-17,20beta,21-triol-3-one functions as a maturation
      inducing hormone and pheromonal precursor in the percid fish, Gymnocephalus
      cernuus.
AB  - Behavioral, biochemical, and electrophysiological studies suggest that the
      trihydroxylated progestin steroid, 4-pregnen-17,20beta,21-triol-3-one (20beta-S)
      stimulates oocyte maturation and pheromone release in the Eurasian ruffe, a
      freshwater percid fish. Behavioral observations found that female ruffe
      undergoing oocyte maturation (OM) release a pheromonal cue that stimulates
      swimming activity and social interactions among conspecific males. Neither
      vitellogenic nor ovulated females released the cue. Pheromone production was
      directly associated with elevated plasma levels of 20beta-S in maturing female
      ruffe which in vitro incubation suggested to be a possible maturation-inducing
      hormone (MIH) in this species along with 4-pregnen-17,20beta-diol-3-one
      (17,20betaP). However, neither of these steroids appear to be the pheromone
      because electrophysiological and behavioral studies found them to lack olfactory
      (EOG) and behavioral activity. Instead, studies of the odor of steroid-injected
      fish suggest the pheromone is a metabolite of 20beta-S. In particular, inter
      peritoneal injection of 20beta-S (but not 17,20betaP) consistently induced
      release of a urinary cue with strong behavioral activity. The pheromone may be a
      highly polar and novel metabolite because it could not be extracted using
      octadecylsilane resin (C18) which has proven effective for other teleost hormonal
      pheromones.

PMID- 15474531
TI  - In vivo and in vitro sex steroids stimulate seabream gonadotropin-releasing
      hormone content and release in the protandrous black porgy, Acanthopagrus
      schlegeli.
AB  - The objective of the present study was to investigate the regulation of seabream
      gonadotropin-releasing hormone (sbGnRH) release using in vivo and in vitro
      approaches in the protandrous black porgy, Acanthopagrus schlegeli. Estradiol
      17beta (E2), testosterone (T), and 11-ketotestosterone (11-KT) were found to
      significantly stimulate the increase of sbGnRH levels in pituitary of black porgy
      after 5-96 h of injection. An in vitro culture system using dispersed brain
      neurons was also developed to investigate the effects of various steroids on
      sbGnRH release. Different doses (10(-6) - 10(-12) M) of E2, T, 11-KT, and
      cortisol were applied during 6 h experiment. KCl stimulated sbGnRH release at a
      dose- and time-dependent manner. The concentration of sbGnRH increased 2-fold in
      the highest dose of KCl treatment compared to the control. Treatments with E2, T,
      11-KT and cortisol significantly stimulated the release of sbGnRH from the
      cultured brain neurons. The concentration of sbGnRH in medium was increased by 2
      , 1.9-, 2.1-, and 4.9-fold when treated with E2, T, 11-KT, and cortisol,
      respectively, as compared to the respective control. Cholesterol did not have any
      stimulatory effects in the release of sbGnRH. The results showed that sex
      steroids and cortisol had direct effect on brain neuronal cells stimulating the
      release of sbGnRH.

PMID- 15474532
TI  - Influence of vasostatins, the chromogranin A-derived peptides, on the working
      heart of the eel (Anguilla anguilla): negative inotropy and mechanism of action.
AB  - We have studied the effects of exogenous human recombinant Vasostatin-1 (VS-1),
      Vasostatin-2 (VS-2) and the human Chromogranin A (CGA) 7-57 synthetic peptides on
      the mechanical performance of the isolated and perfused working eel (Anguilla
      anguilla) heart. Under basal conditions, the three peptides decreased stroke
      volume (SV) and stroke work (SW), thus exerting negative inotropism. The VS-1
      mediated negative inotropism was abolished by exposure to inhibitors of either
      Gi/o protein (pertussis toxin; PTx) or M1 muscarinic receptors (Pirenzepine) or
      calcium (Lantanum and Diltiazem) and potassium (Ba2+, 4-aminopyridine,
      tetraethylammonium, glibenclamide) channels, while it required an intact
      endocardial endothelium (EE). Using NG-monomethyl-L-arginine (L-NMMA) as an
      inhibitor of nitric oxide (NO) synthase (NOS), and hemoglobin as a NO scavenger,
      we demonstrated the obligatory role of NO signaling in mediating the vasostatin
      response. Pretreatment with either a specific inhibitor of soluble guanylate
      cyclase (GC) 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ), or the inhibitor
      of the cGMP-activated protein kinase (PKG) KT5823, abolished the VS-1-mediated
      inotropism, indicating the cGMP-PKG component as a crucial target of NO
      signaling. Of note, VS-1 was effective in counteracting the adrenergic
      (Isoproterenol and Phenylephrine)-mediated positive inotropism. These findings
      provide the first evidence that vasostatins exert cardiotropic action in fish,
      thus suggesting their long evolutionary history as well as their species-specific
      mechanisms of action.

PMID- 15474533
TI  - Androgen effects on plasma GH, IGF-I, and 41-kDa IGFBP in coho salmon
      (Oncorhynchus kisutch).
AB  - Among many species of salmonids, fast growing fish mature earlier than slow
      growing fish, and maturing males grow faster than non-maturing ones. To study the
      potential endocrine basis for this reciprocal relationship we examined the in
      vivo effects of the androgens, testosterone (T) and 11-ketotestosterone (11-KT),
      on plasma growth hormone (GH), insulin-like growth factor-I (IGF-I) and 41-kDa
      IGF binding protein (41-kDa IGFBP) (putative IGFBP-3) in coho salmon,
      Oncorhynchus kisutch. Immature male and female, two-year old fish (avg. wt. 31.7
      +/- 0.63 g) were injected with coconut oil containing T or 11-KT at a dose of
      0.1, 0.25, or 1 microg/g body weight. Blood samples were taken 1 and 2 weeks
      postinjection, and analyzed by immunoassay for T, 11-KT, GH, IGF-I, and 41-kDa
      IGFBP. Steroid treatments elevated the plasma T and 11-KT levels to physiological
      ranges typical of maturing fish. Plasma IGF-I and 41-kDa IGFBP levels increased
      in response to both T and 11-KT in a significant and dose-dependent manner after
      1 and 2 weeks, but GH levels were not altered. These data suggest that during
      reproductive maturation, in addition to the previously demonstrated effects of
      the IGFs on steroidogenesis, the gonadal steroids may in turn play a significant
      role in regulating IGF-I and its binding proteins in fish. The interaction
      between the reproductive and growth axes may provide a regulatory mechanism for
      bringing about the dimorphic growth patterns observed between maturing and non
      maturing salmonids and other species of fish.

PMID- 15474534
TI  - Seasonal change in luteinizing hormone subunit mRNA in Japanese quail and effects
      of short daylength and low temperature.
AB  - Changes in pituitary mRNA levels of LHbeta-subunit (LHbeta) and glycoprotein
      hormone alpha-subunit (common alpha) were investigated in male Japanese quail
      under natural and laboratory conditions to clarify the mechanisms of seasonal
      regulation of luteinizing hormone (LH) secretion. In Experiment 1, birds were
      kept in outdoor cages under natural conditions from August for 12 months. Both
      LHbeta and common alpha mRNA levels decreased rapidly from August to September,
      and after a period of low levels from October through January, they began to
      increase in February and continued to increase until July. There were more
      pronounced seasonal changes in testicular weight and cloacal protrusion width
      with large decreases from August to September and increases from March to May. In
      Experiment 2, birds were kept on laboratory conditions and transferred from long
      to short daylengths at 20 or 9 degrees C and held for 14 days. Although common
      alpha mRNA levels, plasma LH concentrations, testicular weight, and cloacal
      protrusion area decreased on short days without low temperatures, levels of
      LHbeta mRNA did not change. Short daylengths combined with low temperatures
      induced testicular regression and caused decrease in all the parameters measured.
      Low temperatures under long days did not induce any change in the parameters
      significantly. These results suggest that (1) synthesis as well as secretion of
      LH is regulated seasonally, (2) short daylength does not suppress LH synthesis
      completely unless combined with low ambient temperature, and (3) the effect of
      photoperiod on the endocrine system regulating LH secretion is predominant over
      the effect of ambient temperature but ambient temperature acts as an
      environmental cue to terminate reproductive activities at late summer to early
      autumn in Japanese quail.

PMID- 15474536
TI  - Developmental changes of thyroid hormones in the fathead minnow, Pimephales
      promelas.
AB  - The fathead minnow is widely used in ecotoxicological studies and such
      investigations have begun to focus on potential disruption of the thyroid axis.
      However, normal levels of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) and
      their developmental patterns are unknown. To provide these baseline data,
      radioimmunoassays were developed and validated for analysis of T4 and T3 after
      extraction from plasma or whole fish. Female fish showed consistently higher
      plasma levels of T4 than male fish. Analysis of thyroid hormones during
      development showed a significant rise in both T4 and T3 during the pre-hatch
      period, indicating embryonic production of both thyroid hormones. After hatching,
      whole-body content of both T4 and T3 significantly increased in early
      development, peaking at 16 days post-hatch (dph) and 9 dph, respectively, when T4
      reached 32.88 +/- 3.30 ng g(-1) body weight and T3 reached 24.17 +/- 3.15 ng g(
      1) body weight. Thyroid hormones subsequently declined to a low plateau in later
      development with approximately 5 ng g(-1) body weight T4 and 2 ng g(-1) body
      weight T3. These data suggest a prominent role for thyroid hormones in early
      developmental processes when we predict that the ecotoxicological effects of
      thyroid disrupters will be most significant.

PMID- 15474535
TI  - Glucagon and insulin response to dietary carbohydrate in rainbow trout
      (Oncorhynchus mykiss).
AB  - The effects of high carbohydrate (CH) diets on circulating levels of insulin and
      glucagon were studied in rainbow trout (Oncorhynchus mykiss). Fish (76.87 +/-
      8.11 g) were fed for 60 days with three isocaloric diets: control (C) (12% CH), W
      (28% CH mainly from wheat), and S (28% CH from wheat plus gelatinized starch).
      After the diet treatment, trout fed the enriched CH diets showed a higher
      hepatosomatic index and liver glycogen content than controls. In addition, plasma
      glucose levels were also higher but, on the contrary, circulating insulin levels
      were greater in the control group. After the period of diet adaptation, fish were
      sampled 3, 6, 9, and 24 h after food administration. Glycemia levels correlated
      with the dietary carbohydrate content, and were minimum in controls (from 96.02
      +/- 3.77 to 118.97 +/- 6.08 mg/100 ml), followed by W group (from 124.60 +/- 7.46
      to 172.19 +/- 11.36 mg/100 ml) and maximum in the S group (from 133.51 +/- 9.36
      to 217.88 +/- 13.36 mg/100 ml). Postprandial glucagon profiles showed an inverse
      relationship with glycemia, indicating that the ingestion of glucose inhibits
      glucagon secretion. There were no significant differences in postprandial insulin
      levels between groups except for W group, which presented lower levels of
      circulating insulin 9 h after feeding. These results indicate that in trout fed a
      CH diet glucose affects the secretion of glucagon more than insulin during the
      postprandial period.

PMID- 15474537
TI  - Salmon growth hormone receptor: molecular cloning, ligand specificity, and
      response to fasting.
AB  - To better understand the role of growth hormone in regulating fish growth, the
      cDNA of growth hormone receptor (GHR) was cloned from the liver of masu salmon
      (Oncorhynchus masou) and characterized. The masu salmon GHR (msGHR) sequence
      revealed common features of a GHR, including a (Y/F)GEFS motif in the
      extracellular domain, a single transmembrane region, and Box 1 and Box 2 in the
      intracellular domain. However, the amino acid sequence identity was low (49%)
      compared to GHRs of other vertebrates including seven teleosts, and the putative
      msGHR protein lacked one pair of cysteine residues in the extracellular domain.
      To verify the identity of the msGHR, the recombinant protein of the extracellular
      domain was expressed with a histidine tag protein (His-msGHR-ECD), refolded and
      purified for analysis of its ligand specificity. In competition experiments, the
      specific binding between His-msGHR-ECD and radioiodine-labeled salmon GH was
      displaced completely by only salmon GH, and not by salmon prolactin or
      somatolactin. A real-time RT-PCR assay was used to measure salmon GHR mRNA in the
      liver of fed and fasted coho salmon (Oncorhynchus kisutch). The levels of hepatic
      GHR mRNA were lower in fasted fish compared to fed fish after 3 weeks, suggesting
      that GHR gene expression is reduced following a long-term fast. These results
      confirm the identity of the salmon GHR based on ligand specificity and response
      to fasting.

PMID- 15474538
TI  - Localization and expression of aromatase mRNA in adult zebrafish.
AB  - Estradiol plays a key role in the control of many behavioral and physiological
      aspects of reproduction therefore the expression of cytochrome P450 aromatase
      (CYP19), the enzyme responsible for the conversion of androgens to estrogens, is
      of vital interest. The zebrafish, and many other teleosts, have two aromatase
      genes (CYP19A1 and CYP19A2) that are expressed predominantly in the ovary and
      brain, respectively, however, the physiological impact of extra-gonadal aromatase
      has been poorly described. In this study, in situ hybridizations of whole-mount
      and paraffin sections of adult zebrafish brains, pituitaries, and ovarian
      follicles showed that CYP19A2 was strongly expressed in the olfactory bulb (OB),
      ventral telencephalon (TEL), preoptic area (POA), and ventral/caudal hypothalamic
      zone (HT) of the brain, and in the anterior and posterior lobes of the pituitary.
      The regional distribution of the CYP19A2 mRNA did not vary with sex however
      transcript abundance varied within (male "high expressers" had much higher
      expression in the OB, TEL, and HT than in "low expressers") and between sexes
      (higher in OB, TEL, and HT of males than in females). In situ hybridizations of
      CYP19A1 failed to develop a signal in the brain or pituitary but were detectable
      by RT-PCR. CYP19A1 was highly expressed in Stage III B follicles (>500 nm) with
      significantly lower levels in the Stage IV follicles (>680 nm), Stage III A
      follicles (>350 nm), and Stage I and II follicles (350 microm) which were
      embedded in connective tissues. The differential expression of the aromatase
      genes, particularly CYP19A2 in the brain, suggests that the two aromatase genes
      play different roles in the reproductive behavior and/or physiology of bony fish.

PMID- 15474539
TI  - Cloning and analysis of the lamprey GnRH-III cDNA from eight species of lamprey
      representing the three families of Petromyzoniformes.
AB  - The lamprey, which are divided into three families, including the Petromyzonidae,
      Geotriidae, and Mordaciidae, have been shown to regulate the reproductive axis
      through a functional hypothalamic-pituitary-gonadal axis. To date, two forms of
      gonadotropin-releasing hormone (GnRH) have been identified in the sea lamprey
      (Petromyzon marinus), lamprey GnRH-I (decapeptide and cDNA) and lamprey GnRH-III
      (decapeptide), both of which have been shown to be expressed in the preoptic
      anterior hypothalamic region and both forms have been demonstrated to regulate
      reproductive function (i.e. steroidogenesis and gametogenesis). The objective of
      this study was to isolate the cDNA encoding the prepro-lamprey GnRH-III from
      eight species of lamprey using a PCR based subcloning procedure. A degenerate
      primer designed to the lamprey GnRH-III decapeptide was used to amplify the 3'
      end of each transcript, while gene specific primers were used to amplify the 5'
      ends. Phylogenetic analysis using the prepro-lamprey GnRH-III amino acid
      sequences was performed, in which the lamprey GnRH-III sequences divided into
      three groups, supporting the current view of the lamprey lineage at the family
      level. Finally, a phylogenetic analysis of these newly identified deduced amino
      acid sequences together with 64 previously described GnRH sequences suggests that
      the lamprey GnRHs are unique, as they group together separately from the three
      previously described paralogous lineages of the GnRH family.

PMID- 15474540
TI  - The Airline Lifesaver: a 17-year analysis of a technique to prompt the delivery
      of a safety message.
AB  - INTRODUCTION: The Airline Lifesaver (AL) is a 13.3 cm x 9.8 cm card any passenger
      can deliver to the attendant of a commercial airline in order to prompt the
      delivery of an important safety message. In particular, the AL requests the
      following safety--belt reminder be added to the regular announcements given at
      the end of the flight-"Now that you have worn a seat belt for the safest part of
      your trip, the flight crew would like to remind you to buckle-up during your
      ground transportation." METHOD: The AL card was handed to 1,258 flight attendants
      over a 17-year period and compliance with the request for the safety message was
      systematically tracked. Slightly more than one-third of the AL cards (n=460)
      included an incentive for making the announcement. RESULTS: Without the
      incentive, compliance to give the buckle-up reminder was 35.5% of 798 flights.
      With the incentive, compliance was significantly higher (i.e., 53.3%). IMPACT:
      The validity of the AL intervention is discussed with regard to its: (a)
      relevance to cognitive dissonance and consistency theory, and (b) broad-based
      applicability as a component of community-wide efforts to facilitate a safety
      focused culture. The 17-year study also demonstrated a practical and cost
      effective application of a behavior-based incentive program.

PMID- 15474541
TI  - Graduated driver licensing restrictions: awareness, compliance, and enforcement
      in North Carolina.
AB  - PROBLEM: This study examined the extent to which critical restrictions in North
      Carolina's graduated driver licensing (GDL) system are known, adhered to, and
      enforced. METHOD: Teenagers and their parents were recruited as they applied for
      either an intermediate or full license at 1 of 23 licensing offices. Telephone
      interviews were conducted with 900 teenagers and their parents. RESULTS:
      Awareness of North Carolina's night and passenger restrictions was very high
      among both parents and teenagers. Ten percent of teenagers reported violating the
      night restriction without their parents' knowledge, and 15% had done so with
      their parents' approval. Only 4% of parents reported allowing their teenagers to
      drive with more than one teenage passenger, but 19% of teenagers reported that
      they were allowed to do this. Violations of the passenger restriction without
      parental knowledge were more common than violations of the night restriction (22%
      vs. 10%, respectively). Among teenagers who violated restrictions without their
      parents' knowledge, most reported doing so only once or a few times. Teenagers
      expressed little concern about detection, although a majority reported driving
      more carefully to avoid police notice. Neither parents nor teenagers knew much
      about police enforcement of GDL restrictions. To obtain a sense of the views of
      law enforcement officers, informal interviews were conducted with 20 officers
      from five diverse communities and the state highway patrol. These officers were
      highly supportive of GDL but unfamiliar with many of the specific provisions.
      Moreover, enforcement of GDL restrictions did not appear to be a high priority.
      IMPACT ON INDUSTRY: There is a need to increase the belief among teens (and
      parents) that police are enforcing GDL restrictions in their community; law
      enforcement participation in well-publicized traffic safety enforcement efforts
      would likely produce this result.

PMID- 15474542
TI  - Effects of the California graduated driver licensing program.
AB  - PROBLEM: On July 1, 1998, in an effort to ameliorate the problem of high teenage
      driver crash rates, California implemented a graduated driver licensing system
      (GDLS). METHOD: Data on injury crashes of 16- and 17-year-old drivers from a pre
      GDLS year were compared with data from two post-GDLS years. Per-capita crash rate
      ratios were adjusted for changes in crash rates of 25- to 34-year-old drivers,
      who were unaffected by the GDLS. Prevented numbers and 95% confidence intervals
      were estimated. RESULTS: Fatal or severe injury crash rates were significantly
      lower during each of the two post-GDLS years (adjusted rate ratios (RR)=0.72 and
      0.83, for 2000 vs. 1997 and 2001 vs. 1997, respectively). Significant rate
      reductions were observed for all crash types, particularly for struck object
      (RR=0.71 and 0.80, for 2000 vs. 1997 and 2001 vs. 1997, respectively) and non
      collision (RR=0.63 and 0.72, for 2000 vs. 1997 and 2001 vs. 1997, respectively).
      Minor injury crash rates were also lower during post-GDLS years (RR=0.87 and
      0.90, for 2000 vs. 1997 and 2001 vs. 1997, respectively). Percent reductions were
      notably larger during the hours of the late night driving restriction (midnight-5
      a.m.) (RR=0.79 and 0.87, for 2000 vs. 1997 and 2001 vs. 1997, respectively).
      SUMMARY: The implementation of the California GDLS was followed by large
      reductions in the rate of injury-producing motor-vehicle crashes. IMPACT ON
      INDUSTRY: This evaluation supports previous evidence that GDLS is an effective
      countermeasure to adolescent motor-vehicle crashes and their associated injuries.
      States with a traditional licensing system may prevent adolescent driver crashes
      by adopting a GDLS. Future studies should examine factors that influence teenager
      compliance with GDLS provisions and identify approaches to improving compliance.

PMID- 15474543
TI  - The relationship between perceived risk of being ticketed and self-reported seat
      belt use.
AB  - PROBLEM: Twenty-nine percent of Americans failed to use their seat belts in 2000.
      Efforts to improve safety belt usage can be enhanced by identifying specific
      factors that motivate belt use. METHOD: Motorist survey data were used to examine
      the effect of Perceived Risk of being Ticketed (PRT) for a seat belt infraction
      on self-reported seat belt use. RESULTS: Analyses indicated that individuals and
      groups of individuals who have higher PRT typically report higher belt usage.
      Factorial analyses indicated that this perceived risk to belt use relationship
      holds both within groups with generally high (e.g., upper income) and generally
      low (e.g. young men) overall self-reported belt use. DISCUSSION: Applications of
      PRT to improve seat belt use are discussed. IMPACT ON INDUSTRY: Enforcement of
      existing laws, perhaps through selective traffic enforcement programs, and
      strengthening laws to create a higher perception of being ticketed by motorists
      should increase safety belt use thereby saving lives and reducing cost for
      individuals, government, and industry.

PMID- 15474544
TI  - Factors affecting children's participation and amount of labor on family farms.
AB  - METHOD: A two-stage decision-making model is estimated to explain children's
      participation and labor supply on family farms using unitary and cooperative
      bargaining frameworks. RESULTS: Results indicate that parents have different
      preferences about whether their children work and how much they work. The models
      incorporate non-economic factors and allow for different stochastic processes in
      the participation and labor supply decisions. CONCLUSIONS: Concerns about
      children's social development appear to be crucial in deciding children's labor
      participation, while the child's economic contribution significantly influences
      both whether they work and how much they work. Some variables affect the two
      decisions differently. For instance, the higher the parents' education level, the
      higher the probability children will work but the fewer hours they will work.

PMID- 15474545
TI  - Problem driver remediation: a meta-analysis of the driver improvement literature.
AB  - PROBLEM: Given the public safety risk posed by violation and crash repeaters and
      the substantial costs for state driver improvement programs, it is important that
      their effectiveness be scientifically demonstrated and that intervention programs
      are based on sound research findings. METHOD: Crash and traffic violation
      standardized effect sizes (d) representing 106 individual interventions were
      coded from 35 methodologically sound studies and analyzed using meta-analysis.
      RESULTS: Driver improvement intervention in general was associated with small but
      significant reductions in both crashes (dw = 0.03) and violations (dw = 0.06).
      Significant effects were found on both measures for warning letters, group
      meetings, individual hearings, and license suspense/revocation. Of the driver
      improvement interventions studied, license suspension/revocation was by far the
      most effective treatment for both crashes and violations (dw = 0.11 and 0.19).
      Since one of the objectives of license suspension/revocation is to eliminate
      driving for the period of suspension, it is possible that much or all of the
      effect is due to reduced exposure and/or more careful driving during the
      suspension interval. Results were mixed for other types of interventions,
      although distributing educational or informational material was not associated
      with any reductions. Interventions associated with violation reduction tended to
      also be associated with crash reduction, although the relationship was not very
      strong (r = .30). DISCUSSION: Although interpretation of the effect size
      estimates was complicated by almost ubiquitous heterogeneity, the results do
      suggest an overall positive impact of driver improvement interventions in
      general. IMPACT ON INDUSTRY: The results support the continued use of driver
      improvement interventions, chiefly warning letters, group meetings, individual
      hearings, and especially license suspension/revocation. The results also suggest
      that court-triggered traffic violator programs are less effective than
      interventions triggered by drivers license agencies.

PMID- 15474546
TI  - A cross-validation of safety climate scale using confirmatory factor analytic
      approach.
AB  - PROBLEM: Given the lack of a consistent factor structure of safety climate, this
      study tested the stability of a factor structure of a safety climate scale
      developed through an extensive literature review using confirmatory factor
      analytic approach and cross-validation. METHODS: A cross-sectional sample of 722
      U.S. grain industry workers participated in the questionnaire survey. RESULTS:
      The safety climate scale developed through the generation of an item pool based
      on a table of specifications, subsequent scientific item reduction procedures,
      reviews from experts, and pilot test yielded adequate reliabilities for each
      dimension. Each item showed proper discriminative power based on both internal
      and external criteria. Criterion validity was manifested by the significant
      positive correlation of the scale with five criteria. Evidence of construct
      validity was provided by both exploratory and confirmatory factor analyses. Both
      calibration and validation samples supported a consistent factor structure.
      Management commitment and supervisor support were found to influence other
      dimensions of safety climate. DISCUSSION: This study provides an insight into the
      primary reason why previous attempts have failed to find a consistent factor
      structure of safety climate: No specification of the influence of management
      commitment and supervisor support on other dimensions of safety in their models.
      IMPACT ON INDUSTRY: The findings of this study provide a framework upon which
      accident prevention efforts can be effectively organized and underscore the
      importance of management commitment and supervisor support as they affect
      employee safety perceptions.

PMID- 15474547
TI  - Disability among adults injured in motor-vehicle crashes in the United States.
AB  - INTRODUCTION: Little population-based information exists about the long-term
      effects of motor-vehicle crash-related injuries. METHOD: We analyzed data from
      the 1995 National Health Interview Survey Disability (NHIS-D) Supplement to
      estimate the prevalence of crash-related disability among noninstitutionalized
      U.S. adults aged 18 years and older. RESULTS: More than 1.2 million adults were
      living in their homes with the disabling effects of motor-vehicle crash-related
      injuries in 1995. The prevalence of crash-related disability was highest for
      persons in their mid-life years, ages 35-64. Half of the respondents had
      sustained the injuries more than 5 years before the interview. Forty-one percent
      of working-aged individuals reported being unable to work because of their
      disability. CONCLUSIONS: Because crash-related disability is most prevalent
      during the mid-life years, quality of life and productivity may be affected for
      decades. These findings highlight the personal and societal burden associated
      with motor-vehicle crash-related disability in the United States.

PMID- 15474548
TI  - Effects of naturalistic cell phone conversations on driving performance.
AB  - PROBLEM: The prevalence of automobile drivers talking on cell phones is growing,
      but the effect of that behavior on driving performance is unclear. Also unclear
      is the relationship between the difficulty level of a phone conversation and the
      resulting distraction. METHOD: This study used a driving simulator to determine
      the effect that easy and difficult cell phone conversations have on driving
      performance. RESULTS: Cell phone use caused participants to have higher variation
      in accelerator pedal position, drive more slowly with more variation in speed,
      and report a higher level of workload regardless of conversation difficulty
      level. CONCLUSIONS: Drivers may cope with the additional stress of phone
      conversations by enduring higher workloads or setting reduced performance goals.
      IMPACT ON INDUSTRY: Because an increasing number of people talk on the phone
      while driving, crashes caused by distracted drivers using cell phones will cause
      disruptions in business, as well as injury, disability, and permanent loss of
      personnel.

PMID- 15474549
TI  - Organizational influence on working people's occupational noise protection in
      Hong Kong.
AB  - INTRODUCTION: While there is some evidence of the influences of personal
      knowledge and organizational factors on workers' hearing protection, a causal
      model examining relationships between these variables is lacking. METHOD: To
      create and test such a model, this study collected data from 1,701 workers in
      Hong Kong through a random sample telephone survey. RESULTS: Fitting the model to
      the data revealed that organizational regulation of occupational noise protection
      was a root cause of workers' protective behavior, whereas workers knowledge about
      the protection exhibited only a minimal effect. CONCLUSIONS: These findings cast
      doubt on the significance of personal knowledge as a unique factor contributing
      to noise protection. The study also finds that organizational regulation was
      predictable by a number of organizational and industrial factors. IMPACT ON
      INDUSTRY: To prevent occupational deafness, organizational regulation accompanied
      by regular inspection and a norm of noise protection is important.

PMID- 15474550
TI  - Functional analysis of muscarinic acetylcholine receptors using knockout mice.
AB  - Because of the low selectivity of available ligands, pharmacological approaches
      to elucidate the functional difference among muscarinic acetylcholine receptor
      (mAChR) subtypes have been problematic. As an alternative approach, we have
      established a series of mutant mouse lines deficient in each mAChR subtype (mAChR
      KO mice). The systematic analyses of these mice have been useful in revealing the
      functional difference among mAChR subtypes. Here, we review our prior research on
      these mutant mice and also some notable findings reported by other research
      groups.

PMID- 15474551
TI  - Gastrin and interleukin-1beta stimulate growth factor secretion from cultured
      rabbit gastric parietal cells.
AB  - The hormone gastrin stimulates proliferation of the gastric mucosa. Inflammation
      of the stomach is also associated with increased proliferation. The proliferative
      response is important in the reparative response to injury but can be deleterious
      by predisposing to the development of cancer. Parietal cells, but not the cells
      in the proliferative zone of the gastric glands, express the appropriate gastrin
      receptor. Parietal cells may mediate the trophic effects of gastrin by secreting
      other growth factors. The role of parietal cells in the proliferative responses
      has been examined in this study. Rabbit parietal cells were cultured with gastrin
      or the cytokine interleukin-1beta for 18 hours. The conditioned medium from
      gastrin or IL-1beta stimulated parietal cells increased proliferation of HeLa
      cells in an epidermal growth factor-receptor dependant manner. Gastrin and IL
      1beta stimulated the secretion of heparin-binding epidermal growth factor and
      amphiregulin but not transforming growth factor-alpha from parietal cells.
      Combinations of gastrin and IL-1beta on growth factor secretion were synergistic.
      The protein kinase C inhibitor staurosporine abolished these stimulatory effects
      of gastrin and IL-1beta. Divergent effects on histamine-stimulated acid secretion
      were observed; 18 hours pre-treatment with gastrin enhanced acid secretion by 50%
      but IL-1beta inhibited acid secretion in both control and gastrin pre-treated
      parietal cells. The acid-secreting parietal cell plays a central role in the
      regulation of mucosal proliferation in gastric inflammation. Secretion of
      paracrine growth factors by parietal cells may be an important point of
      integration between the endocrine and inflammatory stimuli in determining mucosal
      responses to injury and inflammation.

PMID- 15474552
TI  - Ge-Jee-Bok-Ryung-Hwan induces apoptosis in human cervical carcinoma HeLa cells-
      an endoplasmic reticulum stress pathway--.
AB  - Ge-Jee-Bok-Ryung-Hwan (GJBRH), a commonly used herb formulation in Korea, Japan
      and China, caused a decrease of viability in HeLa human cervical carcinoma cells.
      The treatment of GJBRH resulted in genomic DNA fragmentation as well as the
      increase of Sub-G1 portion in cell cycle analysis. In this study, GFP-Bax over
      expression system showed that Bax, pro-apoptotic Bcl-2 family protein, was
      translocated to mitochondria by the presence of GJBRH. The treatment of BAPTA-AM,
      permeable endogenous calcium chelator, inhibited GJBRH-induced caspase-3 and -9
      activations, the release of cytochrome c and Smac/DIABLO into cytoplasm and the
      resultant cell death in HeLa human cervical carcinoma cells. The treatment of
      BAPTA-AM increased the expression of XIAP, which mediates binding to and
      inhibiting caspases and showed protective effect, in GJBRH-treated cells. GJBRH
      induced the expression of Glucose Response Protein 78 (GRP 78), a positive ER
      stress marker protein. However, BAPTA-AM did not interfere with the ER-stress
      response pathway that triggers the expression of GRP 78. This study showed that
      GJBRH induces cell death, which occurs downstream of or parallel to this point in
      the ER-stress pathway linked to apoptosis. In conclusion, GJBRH induces apoptosis
      in HeLa cells via ER stress-pathway associated mitochondria-dependent apoptosis
      mechansim.

PMID- 15474554
TI  - Inhibition of glucocorticoid-induced cataracts in chick embryos by RU486: a model
      for studies on the role of glucocorticoids in development.
AB  - Cataract formation can be induced by glucocorticoid treatment of developing chick
      embryos. We show here that this response can be blocked very effectively by use
      of the antiglucocorticoid RU486. When dexamethasone (0.02 micromol/egg) was
      administered from day 13 to 16 chick embryos, their lenses (over 80%) became
      cataract (GC-induced cataract; stage IV-V) within 48 hrs. These GC-induced
      cataract formations were prevented by administration of RU486 (0.2 micromol/egg)
      on day 9. However, RU486 also inhibited hatching even though the embryos showed
      normal growth and appearance. In control embryos, more than 90% live chicks
      (39/42 chicks) were hatched on day 22. Chick embryos treated with RU486 on day 9
      appeared to grow normally until 21, but could not hatch. When chick embryos were
      treated with RU486 (0.2 micromol/egg) on day 15, more than 80% live embryos
      (34/42 chicks) were hatched on day 23 with normal appearance, which was one day
      delay comparing to the control. These observations indicate that endogenous
      glucocorticoids are involved in the ability to hatch and that RU486 is able to
      block the actions of endogenous glucocorticoids. Thus, RU486 should be a very
      useful tool for studies on other biochemical and physiological aspects of chick
      embryo development that are under glucocorticoid control.

PMID- 15474553
TI  - The circadian rhythm of 5-HT biosynthetic and degradative enzymes in immortalized
      mouse neuroendocrine pineal cell line--a model for studying circadian rhythm.
AB  - Serotonin (5-HT) plays an important role in circadian rhythm and its level
      decreases at night and increases during day time in pineal gland. This study
      investigates the role of 5-HT biosynthetic and metabolic genes in the circadian
      rhythm using the mouse neuroendocrine pineal cell line (PT811). We first
      determined which type of monoamine oxdiase (MAO) was present in PT811 cells. Our
      results showed that only MAO A, a key which enzyme degrades 5-HT, was present in
      these cells because both 5-HT (the MAO A preferred substrate) and PEA (the MAO B
      preferred substrate) oxidation were sensitive to clorgyline but insensitive to
      deprenyl inhibition. This finding was supported by Northern blot analysis in
      which MAO A, but not MAO B, transcript was detectable. More sensitive
      quantitative RT-PCR showed the presence of both MAO A and MAO B, however there
      was no difference between day and night time. In contrast, the expression of
      tryptophan hydroxylase (TPH, the 5-HT synthetic enzyme), arylalklamine N
      acetyltransferase (AANAT) and Arc (activity regulated, cytoskeleton associated
      protein) genes showed diurnal cycle. AANAT converts 5-HT to N-acetylserotonin,
      leading to the synthesis of melatonin. The Arc gene is an effector early
      immediate gene, regulated by 5-HT. This study suggested that the 5-HT circadian
      rhythm is regulated by TPH and AANAT but not the MAO A gene in this cell line.
      This cell line will be a valuable model for studying the molecular mechanisms of
      circadian rhythm.

PMID- 15474555
TI  - Human keratin 14 driven HPV 16 E6/E7 transgenic mice exhibit hyperkeratinosis.
AB  - Human papillomavirus type 16 (HPV16) has been known as a major causative factor
      for the development of uterine cervical carcinomas. To investigate the in vivo
      activity of HPV16 expressed in squamous epithelia, transgenic mice harboring
      HPV16 E6/E7 with human keratin 14 (hK14) promoter were generated. Grossly, hK14
      driven HPV16 E6/E7 transgenic mice exhibited multiple phenotypes, including
      wrinkled skin that was apparent prior to the appearance of hair in neonates,
      thickened ears, and loss of hair in adults. Transgenic mice with phenotype
      exhibiting severe wrinkled skin and a lack of hair growth died at the age of 3-4
      weeks. Histological analysis revealed that in transgenic mice survived beyond the
      initial 3-4 weeks, HPV16 E6/E7 causes epidermal hyperplasia in multiple
      transgenic lineages with high incidence of transgene penetration. This epithelial
      hyperplasia was characterized by an expansion of the proliferating compartment
      and keratinocytes, and was associated with hyperkeratosis. Such activities were
      significantly higher in the skin of transgenic mice than that of the normal mice.
      Thus, these transgenic mice appeared to be useful for the expression of HPV16
      E6/E7 gene and subsequent analysis on hyperkeratosis.

PMID- 15474556
TI  - Catecholamines are involved in the mechanism of the urinary alcohol level cycle
      in rats fed ethanol intragastrically at a constant rate.
AB  - Studies have indicated that blood alcohol levels cycle exists when ethanol is fed
      continuously using the intragastric feeding rat model of early alcoholic liver
      disease. The aim of the present study was to determine the role played by
      catecholamines in the pathogenesis of the blood alcohol cycling observed when
      ethanol is fed at a constant rate. The rats were tested at the peaks and troughs
      of the urinary alcohol level (UAL) cycle and the results were compared with
      controls. Blood catecholamine levels were markedly increased at the peaks, but
      not at the troughs. Propranolol, a beta adrenergic blocker, attenuated the
      amplitude of the cycle. Phenoxybenzamine, an alpha blocker disrupted the cycle
      and elevated ethanol to fatal levels. The results indicate that both alpha and
      beta adrenergic mechanisms are required for the cycle to occur.

PMID- 15474557
TI  - The role of rat Crry, a complement regulatory protein, in proliferation of
      thymocytes.
AB  - In our previous work we showed that 3F10 monoclonal antibody (mAb), which
      recognizes the rat complement receptor 1-related/gene protein y (Crry), induces
      homotipic aggregation of thymocytes. In this work we studied the effect of 3F10
      mAb on proliferation of rat thymocytes stimulated with concanavalin A (ConA) or
      by cross-linking the T cell receptor (TCR) by anti-alphabetaTCR mAb (R73), in
      vitro, and the mechanisms involved in the process. Our results show that 3F10 mAb
      stimulates proliferation of total thymocytes triggered by suboptimal
      concentrations of ConA or TCR cross-linking, in a dose-dependent manner. Maximal
      stimulation was observed using 10 microg/ml and 20 microg/ml of 3F10 mAb,
      respectively. The 3F10-induced stimulation of thymocytes proliferation in the
      presence of ConA, that was followed by increased production of interleukin-2 (IL
      2), up-regulation of the expression of IL-2 receptor alpha (IL-2Ralpha) and was
      inhibited by anti-CD11a and anti-CD18 mAbs. Purified thymocytes did not respond
      by proliferation to 3F10 mAb, either alone or in combination with R73 mAb or
      ConA. Proliferation of these cells was achieved only in the presence of OX-6+
      antigen-presenting cells (APC) and additional signals transmitted by TCR or ConA.
      These results suggest that Crry is involved in the LFA-1 dependent proliferation
      of thymocytes, a phenomenon that has not been recognized so far.

PMID- 15474558
TI  - Inhibitory effect of GBH on platelet aggregation through inhibition of
      intracellular Ca2+ mobilization in activated human platelets.
AB  - Geiji-Bokryung-Hwan (GBH) was studied on antiplatelet activity in human platelet
      suspensions. GBH consists of the 5 herbs Cinnamomi Ramulus, Poria Cocos, Mountan
      Cortex Radicis, Paeoniae Radix, and Persicae Semen, which have been used in
      herbal medicine for thousands of years for atherosclerosis. The mechanism
      involved in the antiplatelet activity of GBH in human platelet suspensions was
      investigated. GBH inhibited platelet aggregation and Ca2+ mobilization in a
      concentration-dependent manner without increasing intracellular cyclic AMP and
      cyclic GMP. GBH had no inhibitory effect on thromboxane B2 (TXB2) production in
      cell-free systems. Collagen-related peptide (CRP)-induced Ca2+ mobilization is
      regulated by phospholipase C-2 (PLC-gamma2) activation. We evaluated the effect
      of GBH on tyrosine phosphorylation of PLC-gamma2 and the production of inositol
      1,4,5-trisphosphate (IP3). GBH at concentrations that inhibited platelet
      aggregation and Ca2+ mobilization had no effects on tyrosine phosphorylation of
      PLC-gamma2 or on the formation of IP3 induced by CRP. Similar results were
      obtained with thrombin-induced platelet activation. GBH inhibited platelet
      aggregation and Ca2+ mobilization induced by thrombin without affecting the
      production of IP3. We then evaluated the effect of GBH on the binding of IP3 to
      its receptor. GBH at high concentrations partially blocked the binding of IP3 to
      its receptor. Therefore, the results suggested that GBH suppresses Ca2+
      mobilization at a step distal to IP3 formation. GBH may provide a good tool for
      investigating Ca2+ mobilization.

PMID- 15474559
TI  - Antimalarial xanthones from Calophyllum caledonicum and Garcinia vieillardii.
AB  - The antimalarial activity of 22 xanthones against chloroquino-resistant strains
      of Plasmodium falciparum was evaluated. Natural caloxanthone C (1),
      demethylcalabaxanthone (2), calothwaitesixanthone (3), calozeyloxanthone (4),
      dombakinaxanthone (5), macluraxanthone (6), and 6-deoxy-gamma-mangostin (7) were
      isolated from Calophyllum caledonicum. 1,6-dihydroxyxanthone (8), pancixanthone A
      (9), isocudraniaxanthone B (10), isocudraniaxanthone A (11), 2
      deprenylrheediaxanthone B (12) and 1,4,5-trihydroxyxanthone (13) were isolated
      from Garcinia vieillardii. Moreover, synthetic compounds (14-22) are analogues or
      intermediates of xanthones purified from Calophyllum caledonicum (Oger J.M.,
      Morel C., Helesbeux J.J., Litaudon M., Seraphin D., Dartiguelongue C., Larcher
      G., Richomme P., Duval O. 2003. First 2-Hydroxy-3-Methylbut-3-Enyl substituted
      xanthones isolated from Plants: structure elucidation, synthesis and antifungal
      activity. Natural Product Research 17(3), 195-199; Helesbeux J.J., Duval O.,
      Dartiguelongue C., Seraphin D., Oger J.M., Richomme P., 2004. Synthesis of 2
      hydroxy-3-methylbut-3-enyl substituted coumarins and xanthones as natural
      products. Application of the Schenck ene reaction of singlet oxygen with ortho
      prenylphenol precursors. Tetrahedron 60(10), 2293-2300). The relationship between
      antimalarial activity and molecular structure of xanthones has also been
      explored. The most potent xanthones (2), (3) and (7) (IC50 = c.a. 1.0 microg/mL)
      are 1,3,7 trioxygenated and prenylated on the positions 2 and 8.

PMID- 15474560
TI  - Camptothecin, over four decades of surprising findings.
AB  - Camptothecin (CPT) is a modified monoterpene indole alkaloid produced by
      Camptotheca acuminata (Nyssaceae), Nothapodytes foetida, Pyrenacantha klaineana,
      Merrilliodendron megacarpum (Icacinaceae), Ophiorrhiza pumila (Rubiaceae),
      Ervatamia heyneana (Apocynaceae) and Mostuea brunonis (Gelsemiaceae), species
      belonging to unrelated orders of angiosperms. From the distribution of CPT and
      other secondary metabolites, it has been postulated that the genes encoding
      enzymes involved in their biosynthesis evolved early during evolution. These
      genes were presumably not lost during evolution but might have been "switched
      off" during a certain period of time and "switched on" again at some later point.
      The CPT derivatives, irinotecan and topotecan, are used throughout the world for
      the treatment of various cancers, and over a dozen more CPT analogues are
      currently at various stages of clinical development. The worldwide market size of
      irinotecan/topotecan in 2002 was estimated at about $750 million and at $1
      billion by 2003. In spite of the rapid growth of the market, CPT is still
      harvested by extraction from bark and seeds of C. acuminata and N. foetida. All
      parts of C. acuminata contain some CPT, although the highest level is found in
      young leaves (approximately 4-5 mg g(-1) dry weight), approximately 50% higher
      than in seeds and 250% higher than in bark. The development of hairy root
      cultures of O. pumila and C. acuminata, and the cloning and characterization of
      genes encoding key enzymes of the pathway leading to CPT formation in plants has
      opened new possibilities to propose alternative and more sustainable production
      systems for this important alkaloid.

PMID- 15474561
TI  - Selection of high ginsenoside producing ginseng hairy root lines using targeted
      metabolic analysis.
AB  - To develop an experimental system for studying ginsenoside biosynthesis, we
      generated thousands of ginseng (Panax ginseng C.A. Meyer) hairy roots,
      genetically transformed roots induced by Agrobacterium rhizogenes, and analyzed
      the ginsenosides in the samples. 27 putative ginsenosides were detected in
      ginseng hairy roots. Quantitative and qualitative variations in the seven major
      ginsenosides were profiled in 993 ginseng hairy root lines using LC/MS and HPLC
      UV. Cluster analysis of metabolic profiling data enabled us to select hairy root
      lines, which varied significantly in ginsenoside production. We selected hairy
      root lines producing total ginsenoside contents 4-5 times higher than that of a
      common hairy root population, as well as lines that varied in the ratio of the
      protopanaxadiol to protopanaxatriol type ginsenoside. Some of the hairy root
      lines produce only a single ginsenoside in relatively high amounts. These
      metabolites represent the end product of gene expression, thus metabolic
      profiling can give a broad view of the biochemical status or biochemical
      phenotype of a hairy root line that can be directly linked to gene function.

PMID- 15474562
TI  - Hydrophobic metabolites of 2,4-dichlorophenoxyacetic acid (2,4-D) in cultured
      coconut tissue.
AB  - Cultures of inflorescence and plumular tissues of coconut palm (Cocos nucifera
      L.) were maintained in the presence of the auxin, [14C]2,4-dichlorophenoxyacetic
      acid (2,4-D), so that its metabolic fate could be studied. Thin layer
      chromatography of methanol extracts of the plumular tissue showed that four
      classes of metabolites, as well as the unchanged acid, were recovered in the
      extract. In inflorescence tissue, only the unchanged acid and the most polar
      class of metabolites (metabolite I) were recovered. Metabolite I was shown to
      consist mostly of a mixture of sugar conjugates and metabolite II (the next most
      polar) was an unidentified basic metabolite. Metabolites III and IV were both
      novel triacylglycerol analogues in which one of the natural fatty acids was
      replaced with a chain-elongated form of 2,4-D. Reversed-phase thin layer
      chromatography was used to identify the 2,4-D-derived acids and it was found that
      metabolite III contained the 2,4-dichlorophenoxy-moiety attached to a chain
      length of between 2 and 12 carbons, whereas metabolite IV contained 12, 14 and 16
      carbon chain lengths. In inflorescence tissue, and in plumular tissue at low
      sucrose or 2,4-D concentrations and after short periods in culture, metabolite I
      predominated. The other metabolites increased as a percentage when plumular
      culture was prolonged or when sucrose or 2,4-D concentrations were raised. These
      changes correlated with better development of the explant.

PMID- 15474563
TI  - Chemical forms of aluminum in xylem sap of tea plants (Camellia sinensis L.).
AB  - To identify the chemical forms of aluminum (Al) transported from roots to shoots
      of tea plants (C. sinensis L.), 27Al-nuclear magnetic resonance and 19F NMR
      spectroscopy were used to analyze xylem sap. The concentration of Al in collected
      xylem sap was 0.29 mM, twice as high as that of F. Catechins were not detected in
      xylem sap. The concentration of malic acid in xylem sap was higher than that of
      citric acid, whereas the concentration of oxalic acid was negligible. There were
      two signals in the 27Al NMR spectra of xylem sap, a larger signal at 11 ppm and a
      smaller one at -1.5 ppm. The former signal was consistent with the peak for an Al
      citrate model solution, suggesting that an Al-citrate complex was present in
      xylem sap. Although the latter signal at -1.5 ppm was thought to indicate the
      presence of an Al-F complex (at 1.7 ppm) in xylem sap, there was only one signal
      at -122 ppm in the 19F NMR spectrum of xylem sap, indicating that the main F
      complex in xylem sap was F-. These results indicate that Al might be translocated
      as a complex with citrate, while Al-malate, Al-oxalate and Al-F complexes are not
      major Al complexes in xylem sap of tea plants.

PMID- 15474564
TI  - Carotenoid composition in petals of chrysanthemum (Dendranthema grandiflorum
      (Ramat.) Kitamura).
AB  - Sixteen xanthophylls were isolated from the petals of chrysanthemum (Dendranthema
      grandiflorum (Ramat.) Kitamura). Among them, (3S,5S,6R,3'R,6'R)-5,6-dihydro-5,6
      dihydroxylutein (1) and five di-Z geometrical isomers of lutein-5,6-epoxide,
      i.e., 9Z,13'Z (2), 13Z,9'Z (3), 9'Z,13'Z (4), 9Z,13Z (5), and 9Z,9'Z (7), had
      never before been identified as natural products. All of the carotenoids isolated
      from chrysanthemum, except for (9Z)-violaxanthin, are beta,epsilon-carotene
      (alpha-carotene) derivatives. The analyses indicate that carotenoids from the
      petals of chrysanthemum have a very characteristic composition.

PMID- 15474565
TI  - Antimicrobial and cytotoxic agents from Calophyllum inophyllum.
AB  - The study of the chemical constituents of the root bark and the nut of
      Calophyllum inophyllum has resulted in the isolation and characterization of a
      xanthone derivative, named inoxanthone, 3, together with 12 known compounds:
      caloxanthones A, 4 and B, 5, macluraxanthone, 6, 1,5-dihydroxyxanthone, 7,
      calophynic acid, 8, brasiliensic acid, 9 inophylloidic acid, 10, friedelan-3-one,
      11, calaustralin, 12, calophyllolide, 13, inophyllums C, 14 and E, 15. Their
      structures were established on the basis of spectral evidence. Their in vitro
      cytotoxicity against the KB cell line and their antibacterial activity and
      potency against a wide range of micro organisms were evaluated.

PMID- 15474566
TI  - Repellency of essential oils of some Kenyan plants against Anopheles gambiae.
AB  - Essential oils of six plants growing in Kenya were screened for repellent
      activities against Anopheles gambiae sensu stricto. The oils of Conyza newii
      (Compositeae) and Plectranthus marrubioides (Labiateae) were the most repellent
      (RD50=8.9 x 10(-5) mg cm(-2), 95% CI) followed by Lippia javanica (Verbenaceae),
      Lippia ukambensis (Verbenaceae), Tetradenia riparia, (Iboza multiflora)
      (Labiateae) and Tarchonanthus camphoratus (Compositeae). Eight constituents of
      the different oils (perillyl alcohol, cis-verbenol, cis-carveol, geraniol,
      citronellal, perillaldehyde, caryophyllene oxide and a sesquiterpene alcohol)
      exhibited relatively high repellency. Four synthetic blends of the major
      components (present in > or = 1.5%) of the essential oils were found to exhibit
      comparable repellent activity to the parent oils.

PMID- 15474567
TI  - Isolation of an alpha-methylene-gamma-butyrolactone derivative, a toxin from the
      plant pathogen Lasiodiplodia theobromae.
AB  - Lasiodiplodia theobromae is known as a multi-infectious microorganism that causes
      considerable crop damage, particularly to tropical fruits. When the fruits are
      infected by L. theobromae, the typical symptom is the appearance of black spots
      on the surface of the infected fruit. When injected in to the peel of banana, the
      culture filtrate of L. theobromae induced formation of black spots. The structure
      of the isolated compound responsible for this effect was determined to be (3S,4R)
      3-carboxy-2-methylene-heptan-4-olide on the basis of analysis of MS, IR, and 1H
      and 13C NMR spectroscopic data, including HMQC, HMBC, and 1H-1H COSY experiments.
      The active compound was not only isolated from the culture filtrate derived from
      potato dextrose medium, but also from the extract of infected peels of bananas.

PMID- 15474568
TI  - Biosynthesis of gallic acid in Rhus typhina: discrimination between alternative
      pathways from natural oxygen isotope abundance.
AB  - The biosynthetic pathway of gallic acid in leaves of Rhus typhina is studied by
      oxygen isotope ratio mass spectrometry at natural oxygen isotope abundance. The
      observed delta18O-values of gallic acid indicate an 18O-enrichment of the
      phenolic oxygen atoms of more than 30 per thousand above that of the leaf water.
      This enrichment implies biogenetical equivalence with oxygen atoms of
      carbohydrates but not with oxygen atoms introduced by monooxygenase activation of
      molecular oxygen. It can be concluded that all phenolic oxygen atoms of gallic
      acid are retained from the carbohydrate-derived precursor 5-dehydroshikimate.
      This supports that gallic acid is synthesized entirely or predominantly by
      dehydrogenation of 5-dehydroshikimate.

PMID- 15474569
TI  - The fellowship of natural abundance 2H-isotopomers of monoterpenes.
AB  - Site-specific natural abundance hydrogen isotope ratios have been measured by
      deuterium-NMR in a wide variety of monoterpenes from numerous kinds of plants
      grown in different environments. Once the NMR signals have been assigned to the
      whole sets of isotopomers in the different molecules and schemes of connections
      to the parent isotopomers in the geranyl diphosphate (GPP) precursor have been
      defined, a very consistent set of isotopic profiles is evidenced. The results,
      which are incompatible with the mevalonate pathway, can be satisfactorily
      interpreted by considering the deoxyxylulose pathway (DOXP), which is now
      recognized as the usual route for monoterpene biosynthesis in plants. Strong
      deuterium depletion at ex-site 2 of GPP, accompanied by high isotope ratio values
      at site ex-6, are consistent with synthesis of GPP from isopentenyl diphosphate
      (IPP) and dimethylallyl diphosphate (DMAPP) molecules independently produced by
      the DOXP pathway. However, for a given molecular species, significant differences
      are observed as a function of the plant source, in particular at site ex-6 of
      GPP. Thus, monoterpenes from plants with a C3 metabolism are mostly characterized
      by relatively high values of (D/H)6, whereas C4 plants tend to show much lower
      values. This behavior may be attributed to more or less significant contributions
      of GPP resulting from the condensation of IPP with DMAPP produced by
      isomerization. The isotopic profile therefore enables the role of physiological
      and environmental factors on the relative importance of the "independent" and
      "isomerized" model to be estimated. More generally, isotope ratios at individual
      sites in geraniol can be traced back to the corresponding sites in GPP, then to
      sites of the IPP and DMAPP building blocks, then to the pyruvate and
      glyceraldehyde 3-phosphate DOXP active molecules, and finally to the carbohydrate
      photosynthetic precursor. Furthermore, the methylenic hydrogen atoms, which are
      enantiotopic in geraniol, become diastereotopic in chiral, and more specially in
      cyclic, monoterpenes. This provides an isotopic verification for the complete
      stereochemical chain of affiliation, and a way of estimating enantiomeric purity
      and whether intermolecular exchanges have taken place.

PMID- 15474570
TI  - Phragmalin limonoids from Chukrasia tabularis.
AB  - Six phragmalin limonoids, named tabulalin and tabulalides A-E, were isolated from
      the root bark of Chukrasia tabularis (Meliaceae). Their structures were
      determined by spectroscopic methods, and their antifeedant properties evaluated.

PMID- 15474571
TI  - Detection of contour continuity and closure in three-month-olds.
AB  - The present study used an operant conditioning procedure and contour integration
      stimuli to test three-month-olds' sensitivity to both contour continuity and
      contour closure. The data demonstrate an immaturity of continuity detection and a
      lack of closure detection at that age, relative to a previous finding of a
      heightened sensitivity to closed contours in adult observers. This finding
      modifies the general view of infant visual perception that has been more focused
      on the quantitative development of various aspects of visual perception,
      including contrast sensitivity, binocular disparity processing, perceptual
      completion, and other perceptual skills. These results suggest qualitative change
      in terms of the organization of visual information during development, and
      implications of this finding for visual maturation of mechanisms suggested to
      underlie these detection abilities are discussed.

PMID- 15474572
TI  - Effect of stimulus localisation on motion-onset VEP.
AB  - Reliable motion-onset visual evoked potentials (result of the dorsal stream
      activation) were recorded to motion stimuli with the temporal frequency of five
      cycles per seconds in 20 different locations with eccentricity up to 42 degrees
      to periphery of the visual field. Amplitudes and latencies of the positive
      negative-positive (P1-N1-P2; 84-144-208 ms) complex were evaluated in occipital
      (OZ and two derivations 5 cm to the left and right from OZ) and central region
      (CZ) in 10 subjects. We observed: (1) Shortening of the N1 latency toward
      periphery of the visual field. (2) The N1 amplitude maximum and latency minimum
      moved from occipital into central region (CZ derivation) as stimulus moved from
      centre toward periphery of visual field. (3) The P1 and N1 peaks displayed
      significantly greater amplitudes and shorter latencies when the lower part of the
      visual field was stimulated. (4) The N1 peak changed lateralisation of its
      maximum amplitude in dependence on the eccentricity. Up to 17 degrees, it
      corresponds to striate projection of the "optic radiation" whilst more in
      periphery, there was paradoxical lateralisation of higher amplitude and shorter
      latency. The retinotopic dependence shows that the motion response includes
      position information and that the motion-onset VEPs are not generated solely in
      the higher extrastriate areas (MT or MST).

PMID- 15474573
TI  - Spatial integration in structure from motion.
AB  - In three experiments we investigated whether the perception of 3D structure from
      the optic-flow involves a process of spatial integration. The observer's task was
      to judge the 3D orientation of local velocity field patches. In two conditions,
      the patches were presented either in isolation, or as part of a global optic
      flow. In Experiment 1, the global optic-flow was a linear velocity field. In
      Experiment 2, the patches were embedded in a randomly perturbed linear velocity
      field. In Experiment 3, the local patches belonged to a smoothly curved surface.
      The results of these three experiments lead to two main conclusions: (1) a
      process linking spatially separated patches into global entities does affect the
      perception of local surface orientation induced by the optic-flow, and (2)
      linearity or smoothness of the global velocity field are not necessary conditions
      for spatial integration.

PMID- 15474575
TI  - Perceiving depth order during pursuit eye movement.
AB  - Pursuit eye movements alter retinal motion cues to depth. For instance, the
      sinusoidal retinal velocity profile produced by a translating, corrugated surface
      resembles a sinusoidal shear during pursuit. One way to recover the correct
      spatial phase of the corrugation's profile (i.e. which part is near and which
      part is far) is to combine estimates of shear with extra-retinal estimates of
      translation. In support of this hypothesis, we found the corrugation's spatial
      phase appeared ambiguous when retinal shear was viewed without translation, but
      unambiguous when translated and viewed with or without a pursuit eye movement.
      The eyes lagged the sinusoidal translation by a small but persistent amount,
      raising the possibility that retinal slip could serve as the disambiguating cue
      in the eye-moving condition. A yoked control was therefore performed in which
      measured horizontal slip was fed back into a fixated shearing stimulus on a trial
      by-trial basis. The results showed that the corrugation's phase was only seen
      unambiguously during the real eye movement. This supports the idea that extra
      retinal estimates of eye velocity can help disambiguate ordinal depth structure
      within moving retinal images.

PMID- 15474574
TI  - Symmetrical horizontal vergence contributes to the asymmetrical pursuit of
      targets in depth.
AB  - When a target travels slowly and smoothly along the line of sight of one eye, the
      eye that is aligned with the target remains stationary while the other eye
      adducts. The mechanism that is commonly invoked is that commands signaling
      conjugate pursuit and symmetrical vergence are combined. The two signals are in
      the same direction in the adducting eye but are in the opposite direction in the
      stationary eye and, so, cancel. Recent data have challenged this view and the
      idea that the two eyes are controlled independently has been resurrected. Pursuit
      and vergence movements are difficult to separate when they occur together because
      they have similar latencies and dynamics. We have developed a method where
      horizontal vergence is "tagged" by training it to have a vertical vergence
      component that can then be identified in combined pursuit-vergence movements.
      Four subjects trained eye movements to have a vertical vergence component by
      fusing vertical disparities that varied in association with horizontal
      convergence. Following training, the vertical vergence aftereffect was found
      whenever horizontal vergence was stimulated regardless of whether the horizontal
      vergence resulted from movement of the target in the midsagittal plane
      (symmetrical vergence) or from movement of the target along the line of sight of
      one eye (asymmetrical vergence). The vertical vergence aftereffect was never
      observed in association with conjugate movements indicating that asymmetrical
      slow eye movements are not controlled monocularly but contain a vergence
      component along with symmetrical smooth pursuit.

PMID- 15474576
TI  - Attention enhances adaptability: evidence from motion adaptation experiments.
AB  - Several previous psychophysical and neurophysiological studies have investigated
      the separate effects of attention and adaptation on visual processing. Here, we
      investigated the combined effects of attention and adaptation on motion
      processing by measuring the effects of spatial attention on the duration of the
      motion after-effect (MAE) over a wide range of stimulus contrasts. MAE duration
      was compared between two conditions: full-attention, subjects were required to
      pay attention to the adapting motion stimulus, and poor-attention, subjects
      performed a difficult vowel detection task at the center of gaze and ignored the
      adapting motion stimulus. Attention was found to increase the MAE duration by a
      factor of 1.4, which was approximately constant over a wide range of stimulus
      contrasts (3.22-80.6%). Notably, this included contrasts for which the MAE
      duration had reached its asymptotic value. We show that a quantitative model
      based on known properties of directionally selective MT neurons can explain these
      results by assuming that attention enhances the effects of adaptation, a
      phenomenon we refer to as "adaptation gain". Specifically, attending to an
      adapting motion stimulus shifts the semi-saturation point (C50) of the underlying
      contrast response function (CRF) of motion detectors roughly 1.4-fold more to the
      right than does ignoring that same stimulus. By enhancing the effects of
      adaptation in this fashion, attention is predicted to enhance the adaptability of
      the visual motion system.

PMID- 15474577
TI  - Macular pigment and the edge hypothesis of flicker photometry.
AB  - Heterochromatic flicker photometry is commonly used to measure macular pigment
      optical density (MPOD) in the human retina. It has been proposed, and accepted by
      many, that the MPOD so measured represents the value at a retinal location
      corresponding to the edge of the flickering, circular stimulus. We have
      investigated this proposal by using a series of annular stimuli to determine the
      MPOD distribution in the central 1.5 degrees of the retina for both eyes of 10
      subjects. The MPOD obtained using a 1.5 degrees circular stimulus matched the
      MPOD distribution at a retinal eccentricity that was always less than the
      stimulus radius, and averaged, for the 10 subjects, 51% of the stimulus radius.
      Similar results were obtained using a 1 degrees stimulus. Thus the edge
      hypothesis is inconsistent with our data. We suggest that involuntary eye
      movements may be responsible for an apparent edge effect.

PMID- 15474578
TI  - Attentional effects on sensory tuning for single-feature detection and double
      feature conjunction.
AB  - When humans scan their visual environment, relevant objects are selectively
      attended for enhanced processing. It is still unclear in what ways processing is
      modified by attention, and whether attentional selection operates on an
      individual feature (such as colour, orientation or motion) or on binding together
      different features. In the experiments reported in this paper, these two stages
      were characterized using psychophysical reverse correlation. Subjects viewed
      eight patches, briefly flashed and symmetrically arranged around fixation. Each
      patch consisted of segments that could vary in both colour and orientation. One
      of the patches ('target') differed from the remaining 'distractor' patches with
      respect to either its orientation, colour, or both (in three different
      experiments). Subjects were asked to detect the target patch. The stimulus was
      preceded by a cue. On some trials ('cued' trials), the cue informed observers
      that the target patch could only appear at two of the eight possible locations.
      On remaining ('uncued') trials, all eight positions were valid. Psychophysical
      reverse correlation was then applied to derive linear estimates of sensory
      filters for orientation only, colour only, and their conjunction. In line with
      the properties of single neurons in cortex, attentional cueing did not affect
      sensory tuning for detecting individual features. However, it affected the way in
      which features were subsequently (and very inefficiently) combined in a
      multiplicative fashion. The results are consistent with a model in which
      attention recalibrates internal responses to the statistics of the stimulus by
      having signals from different features mutually control each other through
      reciprocal inhibition.

PMID- 15474579
TI  - Preserved gain control for luminance contrast during binocular rivalry
      suppression.
AB  - Binocular rivalry elevates contrast increment thresholds for the detection of a
      transient stimulus presented to the suppressed eye, while thresholds measured
      during dominance are identical to those during monocular viewing (e.g. [Wales,
      R., & Fox, R. (1970). Increment detection thresholds during binocular rivalry
      suppression. Perception and Psychophysics, 8, 90-94]). It is well established
      that contrast increment thresholds depend on reference (pedestal) contrast. With
      high contrasts, increment thresholds increase with pedestal contrast, reflecting
      a gain control with sigmoidal non-linearity. We examined how this gain control
      mechanism operates during binocular rivalry (i.e., with and without perception of
      a pedestal mask). Subjects viewed a horizontal sine-wave grating (steady
      pedestal) and a radial checkerboard dichoptically. When the grating achieved a
      pre-specified phenomenal state (dominance or suppressed), subjects initiated the
      transient presentation (500-ms Gaussian pulse) of a contrast increment of the
      same spatial frequency. The pulse appeared in either the upper or lower half of
      the pedestal. Subjects indicated which half of the pedestal contained the pulse.
      Contrast increment thresholds were measured using a staircase method with various
      pedestal contrasts, which yielded threshold versus contrast (TvC) functions
      during dominance and suppression. The measured thresholds were reliably higher
      during suppression, but the rising slopes of TvC functions did not differ
      significantly between dominance and suppression (i.e., constant upward shift of
      TvC function). A control experiment demonstrated that the TvC function during
      dominance was identical to that during non-rivalry, monocular viewing. Evidently,
      the contrast gain control for transient luminance increment does not require the
      perception of pedestal contrast.

PMID- 15474580
TI  - Motion transparency promotes synchronous perceptual binding.
AB  - While identified regions of human extrastriate visual cortex are functionally
      specialized for processing different attributes of an object, the cognitive and
      neural mechanisms by which these attributes are dynamically bound into integrated
      percepts are still largely mysterious. Here, we report that perceptual
      organization influences the dynamics of binding. Specifically, the perception of
      motion transparency promotes the synchronous perceptual binding of colour and
      motion, which otherwise exhibits considerable asynchronies. In addition, we
      demonstrate that perceptual asynchrony can be reinstated by manipulating
      stereoscopic disparity or speed within the stimulus. Our findings suggest that
      the phenomenology of colour-motion binding parallels the known physiology of
      motion processing in area MT of primate visual cortex, supporting the view that
      the dynamics of perceptual binding is a direct reflection of the time course of
      the underlying neural processing.

PMID- 15474582
TI  - Tenotomy and congenital nystagmus: a failure to answer the wrong question.

PMID- 15474581
TI  - Combining cues in contour orientation discrimination.
AB  - The perceived orientation of a Gabor-patch contour is determined, in part, by
      shifts in carrier phase between the patches [Popple, A. V. & Sagi, D., 2000. A
      Fraser illusion without local cues? Vision Research, 40, 873-878; Popple, A. V. &
      Levi, D. M., 2000a. A new illusion demonstrates long-range processing. Vision
      Research, 40, 2545-2549; Popple, A. V. & Levi, D. M., 2000b. Amblyopes see true
      alignment where normal observers see illusory tilt. Proceedings of the National
      Academy of Sciences of the United States of America, 97, 11667-11672]. Here we
      show that perceived orientation results from the combination of at least three
      stimulus cues: (1) patch orientation, (2) contour envelope orientation, and (3)
      between-patches orientation, which is a function of phase-shifts. In a series of
      three experiments, we investigated how these three cues were combined. The data
      are consistent with weighted cue combination.

PMID- 15474585
TI  - Microarray platforms: introduction and application to neurobiology.

PMID- 15474586
TI  - Experimental design and low-level analysis of microarray data.

PMID- 15474587
TI  - Brain gene expression: genomics and genetics.

PMID- 15474588
TI  - DNA microarrays and animal models of learning and memory.

PMID- 15474589
TI  - Microarray analysis of human nervous system gene expression in neurological
      disease.

PMID- 15474590
TI  - DNA microarray analysis of postmortem brain tissue.

PMID- 15474592
TI  - The evolution of robotic urologic surgery.
AB  - The incorporation of robotics into surgical technology is a relatively recent
      development. Robotic surgical systems can be classified as master-slave systems,
      precise-path systems, or intern-replacement systems. Master-slave systems, the
      most familiar type, were developed from initial experiments in "telepresence"
      surgery funded by the US Department of Defense. Urology has embraced the use of
      commercial robotic surgical systems in a growing number of clinical applications.
      Although drawbacks and limitations exist for the use of surgical robotics, the
      systems are developing rapidly and an expanded role for this technology in the
      future of urology is inevitable. This article reviews the history of the use of
      robotics in surgery, focusing on its specific application to urology.

PMID- 15474593
TI  - The PAKY, HERMES, AESOP, ZEUS, and da Vinci robotic systems.
AB  - In 1965 Gordon Moore, cofounder of Intel Corporation, made his famous observation
      now known as Moore's law. He predicted that computing capacity will double every
      18 to 24 months. Since then, Moore's law has held true; the number of transistors
      per integrated computer circuit has doubled every couple of years. This
      relentless advance in computer technology ensures future advances in robotic
      technology. The ultimate goal of robotics is to allow surgeons to perform
      difficult procedures with a level of precision and improved clinical outcomes not
      possible by conventional methods. Robotics has the potential to enable surgeons
      with various levels of surgical skill to achieve a uniform outcome. As long as
      urologists continue to embrace technological advances and incorporate beneficial
      technology into their practice, the outlook for patients remains bright.

PMID- 15474594
TI  - Overview and fundamentals of urologic robot-integrated systems.
AB  - Advances in technology have revolutionized urology. Minimally invasive tools now
      form the core of the urologist's armamentarium. Laparoscopic surgery has become
      the favored approach for treating many complicated urologic ailments. Surgical
      robots represent the next evolutionary step in the fruitful man-machine
      partnership. The introduction of robotic technology in urology changes how
      urologists learn, teach, plan, and operate. As technology evolves, robots not
      only will improve performance in minimally invasive procedures, but also enhance
      other procedures or enable new kinds of operations.

PMID- 15474595
TI  - Nuances in the optimum placement of ports in pelvic and upper urinary tract
      surgery using the da Vinci robot.
AB  - This article shares the authors' experience in optimizing patient setup, port
      placement, and installation of the robot in various urologic procedures using the
      da Vinci robotic system. The authors give a general description on patient
      positioning, port placement, and installation of the robot with respect to the
      individual operations, followed by an explanation of important nuances, general
      principles, and caveats gained through experience.

PMID- 15474596
TI  - Robotic radical prostatectomy: the European experience.
AB  - Radical prostatectomy is standard treatment for localized prostate cancer in
      young patients. The shortcomings of the laparoscopic approach have led to the use
      of robots to improve the precision and accuracy of anatomic dissection. The
      feasibility of using a remote-controlled robot to perform urologic procedures is
      established, especially for radical prostatectomy. This article reviews the
      European experience with robotic radical prostatectomy.

PMID- 15474597
TI  - Vattikuti Institute prostatectomy, a technique of robotic radical prostatectomy
      for management of localized carcinoma of the prostate: experience of over 1100
      cases.
AB  - Advances in surgical techniques, technology, and surgeons' skills have allowed
      robot-assisted radical prostatectomy to be an option in the management of organ
      confined prostate cancer. The goals of the VIP technique are to cure cancer,
      preserve urinary continence, preserve potency, and decrease morbidity, along with
      the benefits of a minimally invasive surgery and excellent cosmesis. VIP is
      nearly equal to traditional retro-pubic prostatectomy, with certain outstanding
      advantages.

PMID- 15474598
TI  - Robotic radical cystectomy and urinary diversion in the management of bladder
      cancer.
AB  - The authors have explored the versatility of the da Vinci robot for pelvic
      surgery to develop the technique of robotic radical cystectomy in conjunction
      with the Urology and Nephrology Center in Mansoura, Egypt, a world leader in
      conventional (open) cystectomy. This approach, which is designed to minimize the
      time required for surgery, is a sandwich technique in which the cystectomy and
      the neobladder-urethral anastomosis are performed with robotic assistance and the
      urinary diversion is performed extracorporeally. This article reviews the
      published literature and details the authors' current technique of robotic
      radical cystectomy and urinary diversion.

PMID- 15474599
TI  - Robotic renal surgery.
AB  - Robotic technology is an expansion of laparoscopic surgery. Robots can be
      conceived of as specialized laparoscopic tools; their aim is to improve dexterity
      of the operating surgeon, and therefore they correspond to computer-enhanced
      telemanipulator devices. For the patient, the advantage of robotic surgery is
      essentially the advantage of the laparoscopic approach. It gives surgeons
      tremendous benefits, however, with its intuitive Endowrist and dexterity. From
      the patient perspective, the biggest difference is between an open operation and
      one that uses minimally invasive techniques. The contribution of robotics to the
      evolution of surgery will be obvious if these new systems increase the number of
      conventionally trained surgeons performing more complex operations using
      minimally invasive surgical techniques, or if the outcome data from different
      centers worldwide suggest that the use of advanced technology permits surgeons to
      have augmented technical performance.

PMID- 15474600
TI  - Robotic pyeloplasty: technique and results.
AB  - The da Vinci robotic system can be used to perform dismembered and nondismembered
      pyeloplasty techniques effectively. Robotics not only seems to improve dexterity
      and surgical precision but also provides an ergonomic surgical environment for a
      surgeon performing complex reconstructive procedures such as pyeloplasty.
      Although performance-enhancing features of the da Vinci robot seem to decrease
      the difficulty of intracorporeal suturing, a learning curve also exists for
      telerobotic procedures. This learning curve may decrease as experience with
      telerobotics increases and as advances in technology are introduced. Presently,
      the interaction between the primary and assistant surgeon seems crucial to the
      success of the procedure. Although the early clinical experience with robotic
      pyeloplasty is favorable, continuing clinical evaluation and careful follow-up
      are required to determine if the procedure is as efficacious in the long run as
      open pyeloplasty and laparoscopic pyeloplasty.

PMID- 15474601
TI  - Robotically assisted surgery in pediatric urology.
AB  - Robotically assisted laparoscopic surgery likely will be a part of pediatric
      urologic surgery. It will look different than it does now because of technologic
      and procedural innovations. The inherent value of precise visualization, tissue
      handling, and reconstruction, coupled with the reduced morbidity of laparoscopic
      surgery, suggests the potential value of these technologies and methods. Although
      there is much development to be done, the early results are encouraging.
      Pediatric urologists specifically, and pediatric surgical practitioners in
      general, must be involved in the evolution of these techniques and devices, to
      prevent having to adapt adult surgery-oriented systems to pediatric patients.
      Pediatric urologists need to be involved in this development actively to guide
      its course.

PMID- 15474602
TI  - Robotic adrenalectomy.
AB  - The use of robotics in surgery is an emerging field. Robot-assisted laparoscopic
      adrenalectomy has been performed in small numbers worldwide. Advantages of
      robotic assistance over conventional laparoscopy are not acknowledged.
      Improvement in robotic technology, including addition of tactile feedback,
      miniaturization of end-effectors, reduced cost, and advances in remote surgery
      telecommunication technology are awaited.

PMID- 15474603
TI  - Pelvic floor reconstruction: state-of-the-art and beyond.
AB  - Reconstructive surgery for pelvic-floor dysfunction is challenging and complex.
      It requires an extensive familiarity with pelvic anatomy and a wide armamentarium
      of surgical procedures to offer patients with various structural defects. Not
      every patient is suited for every procedure and the surgeon must be able to
      individualize the approach. Each technique has indications and benefits: vaginal
      repairs are relatively simple and cause less morbidity than abdominal repairs,
      which are generally more durable. Laparoscopic repairs provide excellent
      visualization with decreased morbidity, but operative times are longer, there is
      greater cost, and learning curves are steep. Techniques and principles described
      for vaginal and abdominal approaches can be applied to laparoscopic and robotic
      surgery, but comparative outcomes are not available. Robotic assistance with the
      laparoscopic approach may bring this method to the mainstream by helping surgeons
      who are not trained formally in laparoscopy to perform advanced skills. Advances
      in technology and surgical skills will support the application of laparoscopic
      and robotic approaches, and the development of better synthetic and biologic
      materials likely will improve vaginal repairs. Future studies will determine the
      utility of the approach.

PMID- 15474604
TI  - Robot-assisted vasovasostomy.
AB  - Robot-assisted vasovasostomy is an attractive alternative to traditional
      microscopic techniques for several reasons. The normal physiologic tremor is
      removed and greater ease and precision of suture placement is possible. The
      training period or learning curve for robot-assisted vasovasostomy is shorter
      than traditional microscopic techniques. This will allow more surgeons to provide
      quality technical surgical care for their patients. Additional costs are only a
      few hundred dollars. As surgical robots become increasingly available and used
      for a wider variety of procedures, the feasibility of robotic vasovasostomy
      becomes more realistic and vasoepididymostomy is likely. Although robotic surgery
      has improved prostate surgery, its contribution to microsurgical technique has
      the potential for a more profound impact.

PMID- 15474605
TI  - Establishing a robotics program.
AB  - Establishing a successful robotics program requires consideration of several
      issues, including the surgical procedures to be performed, training and
      personnel, facilities, finance, and marketing. This article considers these
      factors from an academic health center standpoint and evaluates the benefits and
      risks of this new technology for urology departments.

PMID- 15474606
TI  - Role of robotics in laparoscopic urologic surgery.
AB  - Robotic surgery is in its infancy. Small series of cases are emerging from
      various centers that indicate a strong role for robotics in the future of
      urology, surgery, and general medicine. Robotic technology is progressing on
      every level and will continue to be a driving force in the progress of science
      and medicine.

PMID- 15474607
TI  - Robotics technology: a journey into the future.
AB  - Some major technologic improvements are needed for robotic technology to reach
      its ultimate potential, which includes better visualization, tactile sensing,
      diagnostic sensing, and miniaturization. This article gives a vision of the
      future of robotic technology with respect to these improvements.

PMID- 15474608
TI  - Ischemia and ischemic tolerance in the brain: an overview.
AB  - Stroke is the third leading cause of death and the leading cause of adult
      disability in the United States. This review outlines the pathways that lead to
      cell death following stroke, and also summarizes the current literature on the
      phenomenon of ischemic tolerance. Ischemic tolerance is an endogenous
      neuroprotective mechanism by which neurons are protected from the deleterious
      effects of brain ischemia that occur during and after stroke. A better
      understanding of the processes that lead to cell death after stroke and
      endogenous neuroprotective mechanisms like ischemic tolerance could help in the
      development of new treatment strategies for this devastating neurological
      disease.

PMID- 15474609
TI  - The neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) and
      methamphetamine on serotonin, dopamine, and GABA-ergic terminals: an in-vitro
      autoradiographic study in rats.
AB  - Damage to serotonin (5-HT) terminals following doses of 3,4
      methylenedioxymethamphetamine (MDMA) is well documented, and this toxicity is
      thought to be related to dopamine release that is potentiated by the 5-HT(2A/2C)
      agonist effects of the drug. Although MDMA and methamphetamine (METH) have some
      similar dopaminergic activities, they differ in their 5-HT agonistic properties.
      It is reasoned that the study of the resultant toxicity following equimolar doses
      of MDMA and METH on both dopamine and 5-HT terminals should offer a comparison of
      the ability of these drugs to induce neurotoxicity. In order to measure the toxic
      effects to the brain, rats were given equimolar doses of MDMA (40 mg/kg/day) and
      METH (32 mg/kg/day) in subcutaneously implanted osmotic minipumps for a period of
      5 days, and in-vitro autoradiography using [3H]-paroxetine, [3H]-mazindol, [3H]
      methylspiperone, and [3H]-flunitrazepam, was performed on brain sections. The
      results showed that METH was more toxic to 5-HT terminals than MDMA in forebrain
      regions, including the anterior cingulate, caudate nucleus, nucleus accumbens,
      and septum. METH was also more toxic than MDMA to dopamine terminals in the
      habenula, and posterior retrosplenial cortex. Therefore, we find that METH was
      more toxic to 5-HT and dopamine terminals in specific brain regions in both pre
      and post-synaptic sites following continuous equimolar dosing.

PMID- 15474610
TI  - Role of ERK activation in cisplatin-induced apoptosis in A172 human glioma cells.
AB  - Cisplatin activates multiple signal transduction pathways associated with cell
      survival and apoptosis in various cell types. The present study was undertaken to
      determine the role of extracellular signal-regulated protein kinase (ERK), a
      member of the mitogen-activated protein kinase family, in cisplatin-induced
      apoptosis in human glioma cells. Cisplatin resulted in apoptosis in a dose- and
      time-dependent manner. Cisplatin-induced apoptosis was prevented by the hydrogen
      peroxide scavenger pyruvate and the antioxidant N-acetylcysteine, but not by the
      superoxide scavenger tiron. Western blot analysis demonstrated that cisplatin
      treatment induced time-dependent activation of ERK, which was inhibited by
      chemical inhibitors of the MEK signaling pathway (PD98059 and U0126) and N
      acetylcysteine. These inhibitors prevented cisplatin-induced cell death.
      Transient transfection of constitutive active MEK1 increased cisplatin-induced
      apoptosis. Cisplatin resulted in a reduction in mitochondrial membrane potential
      and its effect was prevented by N-acetylcysteine and PD98059. Caspase inhibitors
      (Boc-D-FMK and zDEVD-FMK) protected against cisplatin-induced cell death.
      Cisplatin-induced activation of caspase-3 was inhibited by N-acetylcysteine and
      PD98059. Taken together, these findings suggest that the ERK activation plays an
      active role in mediating cisplatin-induced apoptosis of human glioma cells and
      functions upstream of mitochondrial dysfunction and caspase activation to the
      initiate the apoptotic signal.

PMID- 15474611
TI  - Polychlorinated biphenyl mixture aroclor 1254-induced oxidative stress plays a
      role in dopaminergic cell injury.
AB  - Oxidative stress (OS) is thought to participate in the pathogenesis of
      neurodegenerative disorders, including Parkinson's disease (PD). Excessive
      reactive oxygen species (ROS) production can occur during the normal aging
      process or following exposure to environmental toxicants. Dopamine neurons, which
      degenerate during PD, are particularly sensitive to oxidative stress.
      Polychlorinated biphenyls (PCBs), persistent and widespread pollutants, have been
      shown to adversely impact dopaminergic (DAergic) pathways, but the role ROS play
      in neurotoxicity remains unclear. To test the hypothesis that PCB exposure
      compromises dopamine neurons by stimulating ROS production, the direct toxicity
      and oxidative stress response following PCB exposure was examined both in MN9D
      dopamine cells and primary mesencephalic cultures. PCBs induced a time- and
      concentration-dependent increase in ROS production, which preceded cytotoxicity.
      Whereas intracellular GSH depletion exacerbated PCB effects, antioxidant
      pretreatment attenuated ROS production and cell death. Coincident alterations in
      antioxidant defense enzymes also accompanied ROS production, including decreased
      MnSOD and increased CuZnSOD protein levels. The robust elevation in heme
      oxygenase-1 levels further support the activation of oxidative stress mechanisms
      following PCB exposure. Furthermore, PCBs produced concentration-dependent
      reductions in intracellular dopamine levels and elevated dopamine turnover.
      Although the intracellular source of ROS remains unknown, these results suggest
      that sublethal PCB concentrations activate an oxidative stress-related pathway,
      which potentially disrupts dopamine neuron function.

PMID- 15474612
TI  - The influence of milk intake on the lead toxicity to the sensory nervous system
      in lead workers.
AB  - The dietary calcium supplement has been suggested to children and pregnant women
      for prevention of lead toxicity, because of lead-calcium interaction. Lead
      workers were supplied free milk in Taiwan; however, part of workers did not drink
      milk due to lactose intolerance. The goal of this study is to evaluate the
      effects of milk-intake on the peripheral nervous system in workers with long-term
      lead exposure. We measured 181 workers' current perception thresholds (CPT) as
      neurological outcomes. The outcome variables were then correlated to the
      subject's milk intake, blood lead levels, and index of long-term lead exposure
      that was calculated by the subject's serial blood lead data in a period of
      working duration. The potential confounders, including age, gender, body height,
      smoking and alcohol consumption, were also collected and analyzed in multiple
      regressions. 23 workers who reported never or rarely drinking milk, which meant
      that they have suffered from diarrhea or abdomen discomfort after drinking milk
      since childhood, had higher blood lead parameters but not statistically
      significant, and higher thresholds in sensory nerve tests, especially,
      statistically significance on 5 and 250 Hz of hand CPTs, which represent C fiber
      and A-delta fiber. In multiple regression models with control of potential
      confounders, significant protective effects of milk intake were found on reducing
      hand CPTs, but not on foot CPTs. Our study, using measurement of sensory nerve
      CPTs, revealed that drinking milk (two bottles a day, about 700 g per day) might
      have an effect to protect lead peripheral neurotoxicity. The detail biochemical
      mechanisms need further investigations. However, reduction of occupational lead
      exposure is the essential way to protect lead neuropathy. The authors did not
      emphasize that offers of milk to workers could be instead of occupational hygiene
      efforts. Furthermore, lead workers with lactose intolerance might be more
      susceptible, and need more industrial hygiene interventions.

PMID- 15474613
TI  - Study of tyrosine hydroxylase immunoreactive neurons in neonate rats
      lactationally exposed to 2,4-dichlorophenoxyacetic Acid.
AB  - Dopaminergic neurons from the midbrain nuclei substantia nigra (SN; A9) and
      ventral tegmental area (VTA; A10) were investigated by tyrosine hydroxylase (TH)
      immunostaining in neonate rat brains exposed to 2,4-dichlorophenoxyacetic acid
      (2,4-D) through lactation. Dorsal raphe serotonin (5-HT) projections to SN and
      VTA were also studied by 5-HT transporter (5-HTT) immunostaining and results were
      quantified by image analysis. Twenty-five-day-old pups exposed to 2,4-D through
      mothers milk were used. Dams were intraperitoneally administered 70 or
      100mg/kg/day of 2,4-D from the 9th to the 25th postpartum day. After 100mg/kg of
      2,4-D exposure, a 25% diminution in the SN and a 33% diminution in the VTA
      neurons' TH immunostaining along with a significantly 5-HT fiber density
      diminution were observed. The present work supports previous reports which
      suggest that exposure to 2,4-D during development has multiple effects on CNS.

PMID- 15474614
TI  - Thiophene is toxic to cerebellar granule cells in culture after bioactivation by
      rat liver enzymes.
AB  - Several compounds that are not neurotoxic by themselves can cause toxic effects
      in vivo after enzymatic bioactivation. Thiophene is an industrial solvent known
      to produce degeneration primarily of the granule cells in the cerebellum when
      administered to animals in vivo. The mechanism for thiophene toxicity is not
      known, although it has been suggested that thiophene metabolism may lead to
      formation of oxidative intermediates that could function as the ultimate
      toxicants. In the present work we have used rat cerebellar granule cells (CGCs)
      in culture combined with rat liver postmitochondrial (S9) fraction as a source of
      biotransformation enzymes to test the toxicity of thiophene in vitro. The results
      demonstrate that thiophene is toxic to rat cerebellar granule cells in culture
      only after biotransformation. Furthermore, the toxic effects were reduced by
      cytochrome P450 (CYP) inhibitors and by scavengers of reactive molecules (alpha
      tocopherol, reduced glutathione, and phenyl-N-tert-butylnitrone). These findings
      support the hypothesis that thiophene requires metabolism to produce the ultimate
      toxicant, and that the cytochrome P450 enzyme system is involved in the
      metabolism.

PMID- 15474615
TI  - Kinetic and pharmacological characterization of desensitizing and non
      desensitizing glutamate-gated chloride channels in cockroach neurons.
AB  - Glutamate-gated chloride channels (GluCls) are found only in invertebrate nerve
      and muscle, where they mediate inhibitory synaptic transmission, and are
      important target sites of insecticides. Two GluCl subtypes have previously been
      distinguished in isolated cockroach CNS neurons based on differential
      pharmacology. The present study characterizes the kinetics and pharmacological
      properties of desensitizing and non-desensitizing GluCls. Both types of GluCls
      were sensitive to glutamate and ibotenic acid. The non-desensitizing GluCl
      subtype was elicited by glutamate with an EC(50) of 115.8 microM and a Hill
      coefficient of 2.6 and was also sensitive to the agonist ibotenic acid with an
      EC(50) of 42 microM and a Hill coefficient of 1.7. The desensitizing and non
      desensitizing currents were carried by chloride ions, and occurred either
      separately or in combination in individual neurons. The GluCls were also found to
      coexist with and function independently of the GABA-activated chloride channels.
      The desensitizing and non-desensitizing GluCls exhibited different sensitivities
      to the ligand-gated channel blocker picrotoxinin. The desensitizing GluCls were
      blocked only 8% by 30 microM picrotoxinin, whereas the non-desensitizing GluCls
      were potently blocked by picrotoxinin with an IC(50) of 4.1 microM. The
      insecticides fipronil and dieldrin at 1 microM inhibited the desensitizing
      currents by 56 and 13%, respectively, and the non-desensitizing currents by 98
      and 43%, respectively. It is concluded that the two types of GluCls found in
      cockroach neurons exhibit significantly different electrophysiological and
      pharmacological characteristics.

PMID- 15474616
TI  - Hippocampal long-term potentiation (LTP) is reduced by a coplanar PCB congener.
AB  - Neurotoxicity of polychlorinated biphenyls (PCBs) is usually ascribed to the
      ortho-substituted congeners. We have examined the effects of acute perfusion of
      3,3',4,4'-tetrachlorobiphenyl (PCB 77), a coplanar, dioxin-like congener, on long
      term potentiation (LTP) in the Schaffer collateral-CA1 and the mossy fiber-CA3
      pathways in mouse hippocampus. LTP in both pathways was blocked by PCB 77, with a
      threshold effect at a concentration of 1 microM. LTP is a useful model of
      learning and memory function in which a patterned stimulation of an afferent
      pathway produces a persistent increase in the efficacy of synaptic transmission.
      LTP is reduced by PCB mixtures and ortho-substituted congeners at concentrations
      comparable to those studied here. These observations provide evidence in support
      of the hypothesis that dioxin-like and non-dioxin-like PCB congeners are equally
      potent in causing the cognitive decrements seen in children exposed prenatally to
      PCBs.

PMID- 15474617
TI  - Characterization of the role of glutathione in repin-induced mitochondrial
      dysfunction, oxidative stress and dopaminergic neurotoxicity in rat
      pheochromocytoma (PC12) cells.
AB  - Repin, a major constituent in extracts of the plant Centaurea repens is thought
      to be the active principal responsible for the development of equine
      nigropallidal encephalomalacia (ENE), a fatal Parkinson-like neurodegenerative
      disorder in horses. Although the exact mechanism by which ingestion of this weed
      causes ENE is uncertain, a limited body of experimental evidence suggests a
      critical role for the glutathione redox system. In the present study, the
      mechanism of repin neurotoxicity was examined in PC12 cells with a focus on
      determining the role of glutathione (GSH) in repin-induced mitochondrial
      dysfunction, oxidative stress and dopaminergic toxicity. The results demonstrate
      that repin reduced both cellular GSH levels and mitochondrial function in a
      manner that was time- and concentration-dependent. The repin-induced changes in
      GSH levels were found to precede the changes in mitochondrial function. Depletion
      of GSH with a potent GSH depletor (ethacrynic acid (EA)) and a GSH synthesis
      inhibitor (buthionine sulfoximine (BSO)) prior to repin treatment enhanced the
      repin-induced mitochondrial change. In addition, repin caused a concentration
      dependent decrease in cellular dopamine levels in NGF-differentiated PC12 cells.
      Increases in intracellular GSH levels induced by pre-treatment with reducing
      agents (N-acetyl-L-cysteine or reduced glutathione) completely protected the
      cells from repin-induced mitochondrial and dopaminergic toxicity. Antioxidants,
      coenzyme-Q and ascorbic acid completely blocked repin-induced dopaminergic
      toxicity. These data suggest that GSH plays a critical role in repin-induced
      neurotoxicity and that the maintenance of neuronal redox status may prove to be a
      useful strategy for the prevention and/or treatment of ENE. The results support
      the view that GSH depletion, leading to oxidative damage and subsequent
      mitochondrial dysfunction, may serve as a trigger for neuronal cell death.

PMID- 15474618
TI  - Effects of lead exposure on proliferation and differentiation of neural stem
      cells derived from different regions of embryonic rat brain.
AB  - Lead is a potent neurotoxin, causing brain damage and cognitive deficits in
      children even at low exposure levels. Although lead neurotoxicity can occur after
      prenatal or postnatal exposure, little is known of the effects of lead on
      embryonic neural stem cells (NSCs) or the extent to which NSCs originating in
      different brain regions may be differentially sensitive to the effects of lead
      exposure. The present study examined the effects of lead on proliferation and
      differentiation of neural stem cells (NSCs) originating from E15 rat cortex (CX),
      striatum (ST) or ventral mesencephalon (VM). Free-floating neurospheres were
      grown under standard conditions or in lead (0.01-100 microM)-containing
      conditioned media for 5 days and proliferation assessed by 3H-thymidine uptake.
      In other studies, control and lead-exposed neurospheres were collected,
      dissociated and re-plated in control or lead-containing differentiation media for
      7 days. Cells were immunostained for visualization of mature neural and glial
      markers and counted. Lead exposure (0.01-10 microM) had no effect on neurosphere
      viability but caused a significant dose-dependent inhibition of proliferation in
      VM and ST but not CX neurospheres. The number of MAP2 positive neurons
      differentiated from lead-exposed neurospheres of VM and ST origin (but not CX)
      was significantly decreased from control as were the number of oligodendrocytes
      obtained, regardless of their region of origin. In contrast, lead exposure
      significantly increased the number of astrocytes obtained regardless of site of
      origin. These data suggest that even low levels of lead can differentially affect
      proliferation and differentiation of embryonic NSCs originating from different
      brain regions and supports the need for prevention of prenatal lead exposure.

PMID- 15474619
TI  - Physiologically based pharmacokinetic/pharmacodynamic model for the
      organophosphorus pesticide diazinon.
AB  - Diazinon (DZN) is an organophosphorus pesticide with the possibility for
      widespread exposures. The toxicological effects of DZN are primarily mediated
      through the effects of its toxic metabolite, DZN-oxon on acetylcholinesterases,
      which results in accumulation of acetylcholine at neuronal junctions. A
      physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was
      developed to quantitatively assess the kinetics of DZN and its metabolites in
      blood and the inhibition of cholinesterases in plasma, RBC, brain, and diaphragm.
      Focused in vivo pharmacokinetic studies were conducted in male Sprague-Dawley
      rats and the data were used to refine the model. No overt toxicity was noted
      following doses up to 100mg/kg. However, cholinesterases in plasma, RBC, brain
      and diaphragm were substantially inhibited at doses of 50 mg/kg. In plasma, total
      cholinesterase was inhibited to less than 20% of control by 6 h post dosing with
      100 mg/kg. Inhibition of brain acetylcholinesterase (AChE) following 100 mg/kg
      exposures was approximately 30% of control by 6 h. Diaphragm
      butyrylcholinesterase (BuChE) inhibition following 100 mg/kg dosing was to less
      than 20% of control by 6 h. The PBPK/PD model was used to describe the
      concentrations of DZN and its major, inactive metabolite, 2-isopropyl-4-methyl-6
      hydroxypyrimidine (IMHP) in plasma and urinary elimination of IMHP. The fit of
      the model to plasma, RBC, brain, and diaphragm total cholinesterase and BuChE
      activity was also assessed and the model was further validated by fitting data
      from the open literature for intraperitoneal, intravenous, and oral exposures to
      DZN. The model was shown to quantitatively estimate target tissue dosimetry and
      cholinesterase inhibition following several routes of exposures. This model
      further confirms the usefulness of the model structure previously validated for
      chlorpyrifos and shows the potential utility of the model framework for other
      related organophosphate pesticides.

PMID- 15474620
TI  - Re-evaluation of archival material for neuronal cell injury produced by L-2
      chloropropionic acid in the rat brain.
AB  - Previous studies have shown that L-2-chloropropionic acid (L-CPA) produces
      necrosis to cerebellar granule cells with some associated Purkinje cell damage in
      the rat. We have re-evaluated the neuropathology using the original sections and
      fresh sections from archived brain material from rats treated with L-CPA at
      different ages, times after dosing and the following prior treatment with the N
      methyl-D-aspartate (NMDA) receptor antagonist, MK-801. In addition we have
      determined the lobular distribution of cerebellar granule cell necrosis produced
      by L-CPA. Using Fluoro-Jade staining to detect degenerating neurons, we have
      identified three new brain regions that show neuronal cell necrosis as a result
      of exposure to L-CPA, these are the medial habenular nucleus, pontine gray and
      inferior olivary nucleus. The neuronal cell degeneration was confirmed in
      conventional haematoxylin and eosin stained sections and in some cases by glial
      fibrillary acidic protein staining for reactive gliosis. The neuronal cell
      necrosis at these new sites was both time and dose dependent; young 22-day-old
      rats, which are refractory to L-CPA-induced cerebellar granule cell necrosis, did
      however show some neuronal cell degeneration in the medial habenular, pontine
      gray and inferior olivary nuclei. Treatment of rats with MK-801 30 min prior to L
      CPA, afforded complete protection against the neuronal cell injury in the medial
      habenular, pontine gray and inferior olivary nuclei, similar to that previously
      reported for the cerebellum, supporting an excitotoxic mechanism of neuronal cell
      death. In the cerebellum the lobular distribution of the granule cell loss was
      not uniform, more severe granule cell loss occurring in lobules 1-4 and 9a + b.
      This localization exactly mirrors that seen previously in the cerebellum of rats
      given L-CPA and examined by magnetic resonance imaging (MRI). The basis for the
      neuronal cell loss in the medial habenular nucleus, pontine gray and inferior
      olivary nucleus, in addition to the major site in the cerebellum, and the
      sensitivity of particular cerebellar lobes is not currently understood.
      Anatomical connections between the sites of injury and their likely
      neurotransmitter use are discussed.

PMID- 15474621
TI  - Delta-aminolevulinic acid dehydratase (ALAD) polymorphism and susceptibility of
      workers exposed to inorganic lead and its effects on neurobehavioral functions.
AB  - We carried out a cross-sectional study on a group of male workers to determine
      the frequency of delta-aminolevulinic acid dehydratase (ALAD) polymorphisms among
      Chinese, Malays and Indians workers who were exposed to low to medium levels of
      inorganic lead. Also, the association between ALAD1 and ALAD2 genotypes and
      neurobehavioral functions among these workers were investigated. A total of 120
      male workers were studied. Blood and urine were collected for each worker to
      determine the ALAD genotypes, blood lead levels, ALAD, and urinary delta
      aminolevulinic acid (ALAU). ALAD1-1 was the predominant genotype for all three
      ethnic groups while ALAD2-2 was the rarest. The distribution of ALAD1-2 was
      higher among Malays (16.7%) and Indians (14.3%), compared to Chinese (3.6%).
      Selected tests from the World Health Organization Neurobehavioral Core Test
      Battery (WHO-NCTB) were used. Although workers in the ALAD1-1 and ALAD1-2/2-2
      groups had comparable blood lead levels, the 106 workers with ALAD1-1 genotypes
      have significantly higher urinary ALA and significantly poorer neurobehavioral
      scores involving motor dexterity compared with those who have ALAD1-2/2-2
      genotypes (13 workers). It is postulated that the ALAD2 allele may exert
      protective measures against the neurotoxic effects of lead. Further study
      involving a larger cohort of workers with the ALAD2 allele would be needed to
      confirm this hypothesis.

PMID- 15474622
TI  - The concept of quarantine in history: from plague to SARS.
AB  - The concept of 'quarantine' is embedded in health practices, attracting
      heightened interest during episodes of epidemics. The term is strictly related to
      plague and dates back to 1377, when the Rector of the seaport of Ragusa (then
      belonging to the Venetian Republic) officially issued a 30-day isolation period
      for ships, that became 40 days for land travellers. During the next 100 years
      similar laws were introduced in Italian and in French ports, and they gradually
      acquired other connotations with respect to their original implementation.
      Measures analogous to those employed against the plague have been adopted to
      fight against the disease termed the Great White Plague, i.e. tuberculosis, and
      in recent times various countries have set up official entities for the
      identification and control of infections. Even more recently (2003) the proposal
      of the constitution of a new European monitoring, regulatory and research
      institution has been made, since the already available system of surveillance has
      found an enormous challenge in the global emergency of the severe acute
      respiratory syndrome (SARS). In the absence of a targeted vaccine, general
      preventive interventions have to be relied upon, including high healthcare
      surveillance and public information. Quarantine has, therefore, had a rebound of
      celebrity and updated evidence strongly suggests that its basic concept is still
      fully valid.

PMID- 15474623
TI  - Medical treatment of viral pneumonia including SARS in immunocompetent adult.
AB  - Since no randomized controlled trials have been conducted on the treatment of
      viral pneumonia by antivirals or immunomodulators in immunocompetent adults, a
      review of such anecdotal experience are needed for the more rational use of such
      agents. Case reports (single or case series) with details on their treatment and
      outcome in the English literature can be reviewed for pneumonia caused by human
      or avian influenza A virus (50 patients), varicella zoster virus (120),
      adenovirus (29), hantavirus (100) and SARS coronavirus (SARS-CoV) (841). Even
      with steroid therapy alone, the mortality rate appeared to be lower when compared
      with conservative treatment for pneumonia caused by human influenza virus (12.5%
      vs. 42.1%) and hantavirus (13.3% vs. 63.4%). Combination of an effective
      antiviral, acyclovir, with steroid in the treatment of varicella zoster virus may
      be associated with a lower mortality than acyclovir alone (0% vs. 10.3%).
      Combination of interferon alfacon-1 plus steroid, or lopinavir/ritonavir,
      ribavirin plus steroid were associated with a better outcome than ribavirin plus
      steroid (0% vs. 2.3% vs. 7.7%, respectively). Combination of lopinavir/ritonavir
      plus ribavirin significantly reduced the virus load of SARS-CoV in
      nasopharyngeal, serum, stool and urine specimens taken between day 10 and 15
      after symptom onset when compared with the historical control group treated with
      ribavirin. It appears that the combination of an effective antiviral and steroid
      was associated with a better outcome. Randomized therapeutic trial should be
      conducted to ascertain the relative usefulness of antiviral alone or in
      combination with steroid.

PMID- 15474624
TI  - VH3 gene expression in children with HIV infection.
AB  - OBJECTIVE: To study immunoglobulin heavy chain variable region (V(H)) gene
      expression in HIV-uninfected (HIV-) and HIV-infected (HIV+) children. METHODS: A
      retrospective, observational study was performed by PCR-ELISA to examine IgM and
      IgG V(H) gene family expression among peripheral CD19-positive B cells. The
      subjects were 10 HIV+ children with, and 11 HIV+ children without a history of
      invasive pneumococcal disease (IPD) and 12 HIV- children. The ages of the HIV+
      and HIV- children, and the CD4 lymphocyte counts and viral loads (VL) of the HIV+
      /IPD- and HIV+ /IPD- children were statistically similar. Rearranged V(H)3 gene
      libraries were constructed from 3 HIV+ /IPD- children to examine individual gene
      expression. RESULTS: The proportion of IgG V(H)3 expression among HIV+ /IPD- was
      lower than that of HIV- children, but the proportion of IgG V(H)3 expression
      among HIV+ /IPD+ children was not significantly different from that of HIV-
      children. IgG V(H)3 expression was positively, whereas IgM V(H)3 expression was
      inversely correlated with the VL among HIV+ /IPD+, but not HIV+ /IPD- children.
      IgM V(H) gene family expression did not differ between HIV+ and HIV- children.
      CONCLUSION: HIV+ children manifest qualitative and quantitative differences in
      V(H)3 expression, which may be influenced by IPD.

PMID- 15474625
TI  - Lipid lowering effects of statins and fibrates in the management of HIV
      dyslipidemias associated with antiretroviral therapy in HIV clinical practice.
AB  - OBJECTIVES: Dyslipidemia associated with antiretroviral therapy is a common
      clinical problem among HIV-infected patients. Considering that the challenge of
      adherence to drugs (both antiretroviral and lipid lowering) may be substantial in
      routine HIV care, our objective was to evaluate the lipid-lowering effects of
      statins and fibrates in the management of HIV dyslipidemias in clinical practice
      setting. METHODS: Retrospective review of 103 ethnically diverse dyslipidemic HIV
      patients on antiretroviral therapy treated with lipid-lowering drugs (using
      National Cholesterol Education and Prevention II [NCEP II] guidelines) who were
      followed for a median of 70 weeks. RESULTS: An overall mean reduction of 16% in
      total cholesterol, 20% non-HDL cholesterol, and 18% in triglycerides was noted.
      There were no significant changes in HDL levels. On evaluation of the different
      drug classes, the mean (median) change in total cholesterol, were -9 (-7)% with
      fibrates, -11 (-14)% with statins and -23 (-22)% for dual therapy with fibrates
      and statins. The triglycerides decreased by -11 (-40)% in those treated with
      fibrates; -1 (-21)% in those with statins alone, and -32 (-42)% in those with
      dual therapy. Overall less than a fifth of patients reached the defined NCEP
      target goal reduction. On logistic regression analysis, only stopping protease
      inhibitors/ritonavir was independently associated with significant cholesterol
      reduction (OR: 10.14; 95% CI: 2.1-48.9; p < 0.005). CONCLUSION: In a primary care
      setting, the use of statins and/or fibrates may add to the complexity of HIV
      care, with only modest lipid lowering effects.

PMID- 15474626
TI  - Genotypic diversity of Salmonella Enteritidis isolates from sporadic patients in
      limited area during one year.
AB  - OBJECTIVES: Our aims were to investigate the genetic epidemiology of Salmonella
      enterica serovar Enteritidis (S. Enteritidis) isolates using computerized
      analysis of restriction enzyme cleavage patterns. METHODS: A total of 106 S.
      Enteritidis isolates which were collected in Hiroshima Prefecture, Japan in 2001
      were tested by pulsed-field gel electrophoresis (PFGE) using BlnI and XbaI
      enzymes. PFGE profiles were analysed and compared by using Fingerprinting II
      software. RESULTS: BlnI PFGE analysis divided the isolates into 29 genotypes. At
      90% similarity, BlnI cleavage grouped the isolates into 15 genotypes, while XbaI
      cleavage grouped them into only four. Two major clusters, each with a predominant
      genotype, were identified by BlnI cleavage at 42% similarity. In spite of the
      mixed circulation of the two predominant genotypes, one genotype for which a
      number of subtypes were detected was predominant during the first half of the
      year. In contrast, the other genotype, for which no variant subtypes were
      detected, followed during the latter half. The genotypes identified by
      computerized analysis matched well with those judged by visual inspection.
      CONCLUSIONS: The results confirmed the usefulness of PFGE performed with BlnI and
      of the Fingerprinting II software for the genotyping of S. Enteritidis. We think
      that the prevalent characteristics of the predominant genotypes detected here
      were related to the genetic variations of S. Enteritidis.

PMID- 15474627
TI  - Meningitis without a petechial rash in children in the Hib vaccine era.
AB  - AIMS: (1) To determine the causes of meningitis in children immunized with Hib
      vaccine, presenting without a non-blanching rash; (2) to review the use of
      dexamethasone in this group. METHOD: Retrospective review of all children with
      more then 10 white cells/mm(3) in their cerebrospinal fluid (CSF), admitted
      between January 1998 and August 2002. Children were excluded if they had a non
      blanching rash on admission or if their discharge diagnosis was not meningitis.
      Local guidelines recommended dexamethasone to be given before antibiotics for
      children with meningitis and no rash. RESULTS: One hundred and eight children
      were identified. Causes of proven meningitis were: viral 41 (enterovirus 40),
      bacterial 22. CSF culture or PCR was the only diagnostic test in 31 children.
      Dexamethasone was given to 16 children. Length of admission was shorter in
      children with viral compared with bacterial meningitis (4 vs 8 days; P < 0.0001).
      SUMMARY: Viral meningitis is the commonest cause of meningitis without rash.
      Enteroviral PCR was the most useful test and needs to be widely available.
      Confirmation of enteroviral meningitis allowed early discharge. Few children were
      given dexamethasone, but only 5/108 may have benefited. CONCLUSIONS: The most
      common cause of meningitis without a rash in British children is enterovirus. The
      use of dexamethasone in children with meningitis without a rash should be
      reconsidered or, at least, individualised.

PMID- 15474628
TI  - Resolution of symptoms in patients with community-acquired pneumonia treated on
      an ambulatory basis.
AB  - OBJECTIVE: To describe the resolution of five symptoms commonly associated with
      community-acquired pneumonia (CAP). METHODS: Three hundred and ninety-nine
      patients with CAP (Fine Classes I to III) recorded the severity (from 0 to 5) of
      fatigue, cough, dyspnoea, sputum, and pleuritic chest pain daily from enrollment
      to day 14 and also on days 30 and 42. A total symptom score was obtained by
      multiplying an individual score by four and summing the score of the five symptom
      (transformed score). A total symptom score of <or= 20 or an individual symptom
      untransformed score of <or= 1 was defined as resolution. RESULTS: The mean
      untransformed symptom scores at the time of presentation were: fatigue (3.5 +/-
      1.4), cough (3.5 +/- 1.5), dyspnoea (2.7 +/- 1.5), sputum production (2.2 +/-
      1.6) and chest pain (2.1 +/- 1.7). Sixty-seven percent had resolution of symptoms
      by day 14. When the study population was divided according to a mean total
      symptom score of <or= 20 or > 20 on day 14, the patients with a score > 20 (n =
      122; 33%) had higher symptom scores at all time points out to 42 days. The median
      time to return to work was 6 days. CONCLUSION: The pneumonia symptom severity
      score is a useful tool for advising patients regarding the time to symptomatic
      resolution of pneumonia.

PMID- 15474629
TI  - Acanthamoeba pathogenicity for corneal cells.
AB  - OBJECTIVES: Comparison of the relative susceptibility of human keratocyte and
      corneal epithelial cells to Acanthamoeba castellanii. METHODS: Primary cultures
      of the mammalian cells were utilised at equivalent concentrations throughout the
      co-incubations. Preliminary experiments involved visual estimation of the effects
      of 10-fold dilutions of Acanthamoeba trophozoites after various time intervals.
      Formal quantative assessment was performed by image analysis of the respective
      effects of the Acanthamoeba at a concentration of 10(6)/ml/well following 3, 6, 9
      and 24 h of co-incubation. RESULTS: Epithelial cells were relatively resistant to
      the cytopathic effects of Acanthamoeba throughout the experiments course at all
      concentrations tested: the cut-off point, below which no effect was observed, was
      also greater. Formal assessment by image analysis confirmed these impressions
      while revealing that the relative resistance of epithelial cells was confined to
      the initial phases of co-incubation. For both mammalian cell types the first
      observable sign of cell damage was cell shrinkage with the formation of
      retraction fibres and gaps. CONCLUSIONS: The relative resistance of epithelial
      cells to Acanthamoeba may be due to difficulty in initiating attack of a
      monolayer with tight junctions between cells. These results provide
      circumstantial evidence of the importance of the corneal epithelium in the
      prevention of amoebic invasion. SUMMARY: The relative susceptibility of cultured
      corneal epithelial cells and keratocytes were compared as regards both the
      concentration of amoebae required to produce obvious cell damage and the area of
      cells destroyed for a given concentration at various time intervals. The
      epithelial cells were more resistant than keratocytes with respect to both
      factors, at least early in the co-incubation period. This may be related to the
      different growth patterns of the cell types as epithelial cells form a monolayer
      connected by tight junctions and indirectly supports the idea that the epithelium
      forms an important barrier function against invasion in vivo.

PMID- 15474630
TI  - Predictors of adverse outcome from candidal infection in a tertiary care
      hospital.
AB  - OBJECTIVES: To retrospectively delineate predictors of adverse outcome by looking
      at the demographic features, therapy and outcome of systemic candida infection in
      a large tertiary care university-affiliated medical center. METHODS: We reviewed
      the clinical data on 186 inpatients with candidemia over a 6-year period. The
      major reason for their hospital admission was an underlying malignancy or an
      infection other than candidemia. RESULTS: Candida albicans, tropicalis,
      parapsilosis, glabrata and krusei caused 54, 22, 13, 8 and 3% of the candidemia
      episodes, respectively. The overall mortality was 42% and it was highest in
      patients suffering from candidemia of the glabrata species (73%). Forty-eight
      (63%) of the 76 patients who received no anti-fungal treatment died compared to
      38 (34%) of 110 patients who were treated (P < 0.05). Predictors of adverse
      outcome were intensive care unit stay, renal failure, thrombocytopenia and the
      need for mechanical ventilation or inotropic support. CONCLUSIONS: We identified
      four predictors of mortality from candidemia infection. Their validity should be
      further assessed and the specific candida strains and their susceptibility need
      to be methodically identified. Our data support immediate initiation of therapy
      at first identification of infection.

PMID- 15474631
TI  - Jejunal perforation caused by morphologically abnormal Taenia saginata saginata
      infection.
AB  - We report a case of jejunal perforation caused by infection with taeniid tapeworm
      possessing unusual morphology that has not been previously described. Among five
      cestodes recovered during operation, one exhibited a bifurcation at the posterior
      end and the other harbored a lateral branching of immature segments from the main
      strobila. By sequence analysis of the mitochondrial cytochrome c oxidase I gene
      and the 28S rRNA gene has confirmed them to be Taenia saginata saginata.

PMID- 15474632
TI  - Sudden infant death syndrome due to parainfluenza virus 2 associated with
      hemophagocytic syndrome.
AB  - We report a child with Sudden Infant Death Syndrome (SIDS), aged 16 months. The
      histological findings of tonsils, spleen, and bone marrow revealed many
      hemophagocytic cells. Parainfluenza virus type 2 (PIV2) was cultured in the
      nasopharynx and detected by reverse-transcription (RT)-PCR in liver tissue and
      bone marrow. His laboratory data of elevated level of ferritin and IL-6 suggested
      hemophagocytic syndrome (HPS). It is suspected that PIV2 infection in infants is
      a risk factor for SIDS.

PMID- 15474633
TI  - Preventing suicide in primary care patients: the primary care physician's role.
AB  - Suicide is a critical public health problem that primary care physicians
      potentially can help address given that distressed patients frequently visit them
      in the weeks and months preceding the successful suicide. This article considers
      factors placing the patient at high risk for successful suicide and clinical
      assessment techniques available to the primary care physician. Patients who wish
      to harm themselves but still lack an articulated plan for doing so can be treated
      by the primary care physician with the monitoring assistance of a depression care
      manager and appropriate consultation by a mental health specialist.

PMID- 15474634
TI  - Mental health service use 1-year after the World Trade Center disaster:
      implications for mental health care.
AB  - The objective of this study was to assess prevalence and predictors of mental
      health service use in New York City (NYC) after the World Trade Center disaster
      (WTCD). One year after the attacks, we conducted a community survey by telephone
      of 2368 adults living in NYC on September 11, 2001. In the past year, 19.99% (95%
      confidence interval [CI]=18.2-21.77) of New Yorkers had mental health visits and
      8.1% (95% CI=7.04-9.16) used psychotropic medications. In addition, 12.88% (95%
      CI=11.51-14.25) reported one or more visits were related to the WTCD. Compared to
      the year before, 8.57% (95% CI=7.36-9.79) had increased post-disaster visits and
      5.28% (95% CI=4.32-6.25) had new post-disaster treatment episodes. Psychotropic
      medication use related to the WTCD was 4.51% (95% CI=3.75-5.26). Increased post
      disaster medication use, compared to the year before, was 4.11% (95% CI=3.35
      4.86) and new medication episodes occurred among 3.01% (95% CI=2.34-3.69). In
      multivariate logistic analyses, mental health visits were associated with younger
      age, peri-event panic attack, posttraumatic stress disorder (PTSD) and
      depression. In addition, WTCD-related visits had a positive "dose-response"
      association with WTCD event exposures (P<0.0001). WTCD-related visits also were
      positively associated with peri-event panic, anxiety, lower self-esteem, PTSD,
      and depression. All three medication measures were positively related to PTSD and
      depression, and negatively associated with African American status. WTCD-related
      medication use also was positively related to younger age, female gender, WTCD
      event exposures, negative life events, anxiety and lower self-esteem. Finally,
      while the percentage of New Yorkers seeking post-disaster treatment did not
      increase substantially, the volume of visits among patients apparently increased.
      We conclude that exposure to WTCD events was related to post-disaster PTSD and
      depression, as well as WTCD-related mental health service use. African Americans
      were consistently less likely to use post-disaster medications. Although the WTCD
      did have an impact on treatment-seeking among current patients, it did not
      substantially increase mental health treatment among the general population.

PMID- 15474635
TI  - Hospital preparedness for possible nonconventional casualties: an Israeli
      experience.
AB  - Since 9/11, hospitals and health authorities have been preparing medical response
      in case of various mass terror attacks. The experience of Tel Aviv Sourasky
      Medical Center in treating suicide-bombing mass casualties served, in the time
      leading up to the war in Iraq, as a platform for launching a preparedness program
      for possible attacks with biological and chemical agents of mass destruction.
      Adapting Quarantelli's criteria on disaster mitigation to the
      "microinfrastructure" of the hospital, and including human behavior experts, we
      attempted to foster an interactive emergency management process that would deal
      with contingencies stemming from the potential hazards of chemical and biological
      (CB) weapons. The main objective of our work was to encourage an organization
      wide communication network that could effectively address the contingent hazards
      unique to this unprecedented situation. A stratified assessment of needs,
      identification of unique dangers to first responders, and assignment of team
      training sessions paved the way for program development. Empowerment through
      leadership and resilience training was introduced to emergency team leaders of
      all disciplines. Focal subject matters included proactive planning, problem
      solving, informal horizontal and vertical communication, and coping through
      stress-management techniques. The outcome of this process was manifested in an
      "operation and people" orientation supporting a more effective and compatible
      emergency management. The aim of article is to describe this process and to point
      toward the need for a broad-spectrum view in such circumstances. Unlike military
      units, the civilian hospital staff at risk, expected to deal with CB casualties,
      requires adequate personal consideration to enable effective functioning. Issues
      remain to be addressed in the future. We believe that collaboration and sharing
      of knowledge, information, and expertise beyond the medical realm is imperative
      in assisting hospitals to expedite appropriate preparedness programs.

PMID- 15474636
TI  - Childhood adversity and frequent medical consultations.
AB  - We assessed possible psychological mediators of the relationship between
      childhood adversity and frequent medical consultations among new outpatients at
      neurology, cardiology, and gastroenterology clinics. We assessed whether these
      differed in patients with and without organic disease that explained their
      symptoms. At first clinic visit we recorded Hospital Anxiety and Depression scale
      (HADS--anxiety and depression subscale scores), Illness Perception Questionnaire
      (IPQ--four subscales: consequences, cure, identity, timeline), Health Anxiety
      Questionnaire (total score), and Symptom Amplification Scale (total score).
      Subjects were divided into two groups according to whether they had experienced
      any type of childhood adversity using the Childhood Experience of Care and Abuse
      Schedule. Outcome was the (log) number of medical consultations for 12 months
      before and 6 months after the index clinic visits. Multiple regression analysis
      was used to determine mediators; this was performed separately for patients with
      symptoms explained and not explained by organic disease. One-hundred and twenty
      nine patients (61% response) were interviewed. Fifty-two (40.3%) had experienced
      childhood adversity; they made a median of 16 doctor visits compared with 10 for
      those without adversity (adjusted P=.026). IPQ identity score (number of symptoms
      attributed to the illness) and HAD depression scores were significantly
      associated with both childhood adversity and number of medical consultations and
      these variables acted as mediators between childhood adversity and frequency of
      consultation in the multiple regression analyses. This association was limited to
      patients with medically unexplained symptoms and was mediated by IPQ Identity
      Score (number of symptoms attributed to the patient's illness) and HAD depression
      score. Sexual abuse and overt neglect were the adversities most closely
      associated with frequent consultations. In patients with medically unexplained
      symptoms the association between childhood adversity and frequent medical
      consultations is mediated by the number of bodily symptoms attributed to the
      illness. Psychological treatments should be targeted at these patients with a
      view to reducing their frequent doctor visits.

PMID- 15474637
TI  - Modeling crisis decision-making for children in state custody.
AB  - We studied 1492 children in state custody over a 6-month period to investigate
      the relationship between children's hospital admissions and the crisis workers'
      clinical assessment. A 27-item standardized decision-support tool [the Childhood
      Severity of Psychiatric Illness (CSPI)] was used to evaluate the symptoms, risk
      factors, functioning, comorbidity, and system characteristics. The CSPI has been
      shown to have a reliability range from 0.70 to 0.80 using intraclass
      correlations. Logistic regression was used to calculate age-adjusted odds ratios
      (AOR) of hospitalization, their 95% confidence intervals, and corresponding P
      values. The results showed that risk factors, symptoms, functioning,
      comorbidities, and system characteristics were all associated with hospital
      admissions. Children with a recent suicide attempt, severe danger to others, or
      history of running away from home/treatment settings were more likely to be
      hospitalized (respective AOR=12.7, P<.0001; AOR=32.3, P<.0001; AOR=3.0, P=.001).
      In addition, hospitalization was inversely associated with caregiver knowledge of
      children (AOR=0.2, P=.01) and multisystem needs (AOR=0.3, P=.04). The decision to
      hospitalize children psychiatrically appears to be complex. As predicted, risk
      behaviors and severe symptoms were independent predictors of children's hospital
      admissions. Interestingly, the capacity of the caregiver and the children's
      involvement in multiple systems also predict children's hospital admissions.

PMID- 15474638
TI  - A prospective study to compare three depression screening tools in patients who
      are terminally ill.
AB  - Depression is a significant symptom for approximately one in four palliative care
      patients. This study investigates the performance of three screening tools.
      Patients were asked to verbally rate their mood on a scale of 0-10; to respond
      "yes" or "no" to the question "Are you depressed?," and to complete the Edinburgh
      depression scale. They were also interviewed using a semi-structured clinical
      interview according to DSM-IV criteria. Complete data was available for 74
      patients. For the single question, a "yes" answer had a sensitivity of 55% and
      specificity 74%. The Edinburgh depression scale at a cut-off point of > or =13
      had a sensitivity of 70% and specificity of 80%. The verbal mood item with a cut
      off point of > or =3 had a sensitivity of 80% and specificity of 43%. The
      Edinburgh depression scale proved to be the most reliable instrument for
      detecting clinical depression in palliative care patients.

PMID- 15474639
TI  - Olfactory-triggered panic attacks among Cambodian refugees attending a
      psychiatric clinic.
AB  - Olfactory panic attacks have not been systematically assessed in a psychiatric
      population by any previous studies. Among Cambodian refugees attending a
      psychiatric clinic, the present investigation determines the following: (a) 1
      month current prevalence of olfactory-triggered panic attacks, (b) associated
      psychopathology (Hopkins Symptom Checklist and the Structured Clinical Interview
      for DSM-IV-diagnosed posttraumatic stress disorder [PTSD]), and (c) frequency in
      events of olfactory panic of catastrophic cognitions (Panic Attack Cognitions
      Scale [PACQ]) and flashbacks (Clinician-Administered PTSD flashback scale). Forty
      five percent of 100 consecutive psychiatric patients were found to have suffered
      an olfactory-triggered panic attack in the previous month; having current
      olfactory panic attacks was highly correlated with psychopathology (e.g., to PTSD
      diagnosis: and chi(2)=50.0; df=1; p<.001); and during olfactory-triggered panic
      attacks, catastrophic cognitions and flashbacks were common. Possible mechanisms
      for generation of high rates of olfactory-triggered panic attacks in this
      population are discussed (the "traumatic memory/catastrophic
      cognitions/interoceptive conditioning/escalating arousal" or "TCIE" model of
      panic generation) as are treatment implications.

PMID- 15474640
TI  - Increased depression and anxiety in infertile Japanese women resulting from lack
      of husband's support and feelings of stress.
AB  - We report that infertile women in Japan as well as in the Western world have high
      levels of emotional distress, anxiety, and depression. The reasons for anxiety
      and depression in infertile women are easy to presume but remain unclear. We
      conducted the present study to assess the relationship between the anxiety and
      depression of infertile Japanese women and their thought processes and emotional
      well-being with regard to their infertility. A cross-sectional questionnaire was
      administered to 101 infertile Japanese women who visited the infertility clinic
      at Tokai University. Inventories included the Hospital Anxiety and Depression
      Scale (HADS) and our original infertility questionnaire, which is composed of 22
      questions to assess attitudes and emotional status in facing the stigma of
      infertility. After factor analysis, comparison between the HADS and the
      infertility questionnaire was made with simultaneous multiple regression
      analyses. Anxiety and depression in childless Japanese women were significantly
      associated with lack of husband's support and feeling stress. Our findings should
      prove useful in designing and implementing psychological support programs for
      infertile Japanese women. Psychological interventions to relieve or diminish
      these conditions might have significant therapeutic benefits for women attending
      infertility clinics in Japan.

PMID- 15474641
TI  - Medical screening in the emergency department for psychiatric admissions: a
      procedural analysis.
AB  - Patients who are admitted to psychiatric inpatient wards often undergo a medical
      screening examination in the emergency department to rule out serious or
      underlying medical conditions that may be better treated elsewhere.
      Unfortunately, prior research has been conflicting on the relative merits of
      various screening procedures, making it difficult to implement guidelines. A
      systematic review of the literature was undertaken to research the current state
      of knowledge in medical screening procedures. Electronic searches were conducted
      in PubMed, MEDLINE, and the Cochrane Library for publication years 1966-2003. No
      restrictions were placed on language or on quality of publications. Twelve
      studies were found that reported specific yields of various screening procedures.
      Results indicate that medical history, physical examination, review of systems,
      and tests for orientation have relatively high yields for detecting active
      medical problems in patients presenting with psychiatric complaints. Routine
      laboratory investigations generally have a low yield for clinically significant
      findings. However, these should be added selectively for four groups at higher
      risk of serious medical conditions, i.e., the elderly, substance users, patients
      with no prior psychiatric history, and patients with preexisting medical
      disorders and/or concurrent medical complaints.

PMID- 15474642
TI  - Laboratory findings in emergently medicated psychiatry patients.
AB  - OBJECTIVE: To determine routine laboratory differences between patients with
      severe psychomotor agitation who require emergency intramuscular (IM-medicated
      patients) medication and those who do not (non-IM-medicated patients). METHOD: A
      retrospective chart review of patients 18 years or older who went to a psychiatry
      emergency service over a 30-day period was performed. Demographic and laboratory
      variables were compared between IM- and non-IM-medicated patients. RESULTS:
      Emergently medicated patients (n=35) were older than non-IM-medicated patients
      (n=179) (42.6 vs 34.3 years, P<.001). Patients receiving emergency IM medications
      had higher leukocyte (WBC) count (P=.04), blood urea nitrogen (P=.001),
      creatinine (P=.01), glucose (P=.009), aspartate aminotransferase (P<.001),
      alanine aminotransferase (P=.01), and electrocardiogram QTc interval (P=.03).
      They were also more likely to have abnormal levels of potassium (P<.05), glucose
      (P<.05), aspartate aminotransferase (P<.001), and alanine aminotransferase
      (P<.05). CONCLUSIONS: Emergently medicated patients in this psychiatry emergency
      service were more likely to be older and more likely to have abnormal
      laboratories vs other adult patients.

PMID- 15474643
TI  - Fibromyalgia, borderline personality, and opioid prescription.

PMID- 15474644
TI  - Comment on "essential background reading for clinical decision making".

PMID- 15474645
TI  - Effects of the cholinesterase inhibitors donepezil and metrifonate on scopolamine
      induced impairments in the spatial cone field orientation task in rats.
AB  - The aim of these experiments was to assess whether the clinically validated
      cognition enhancers donepezil (Aricept, E2020) and metrifonate antagonize
      scopolamine-induced deficits in the cone field, a complex spatial discrimination
      task. The cone field task allows measurement of the effects of experimental
      manipulations on working and reference memory (WM and RM), search strategies, and
      on the speed and latency to execute the task. The effects of a single
      administration of donepezil (0.1, 0.3, and 1.0 mg kg(-1), p.o.) and metrifonate
      (30, 60, and 120 mg kg(-1), p.o.) were investigated in adult Harlan-Wistar rats
      trained to a stable level of performance and pretreated with scopolamine (0.5 mg
      kg(-1), i.p. 30 min before training). Scopolamine impaired WM without inducing
      overt non-cognitive side-effects. Donepezil did not antagonize the scopolamine
      induced deficits, whereas metrifonate antagonized the WM deficits at the dose of
      60 mg kg(-1), but not at 30 or 120 mg kg(-1). Thus, a cholinesterase inhibitor
      with proven clinical efficacy can antagonize scopolamine-induced spatial memory
      deficits. The cone field would be a useful component of a behavioral screening
      battery to test the effects of putative cognition enhancers.

PMID- 15474646
TI  - Behavioural sensitization to nicotine precedes the onset of nicotine-conditioned
      locomotor stimulation.
AB  - Context-dependent behavioural sensitization to nicotine develops faster and is
      more robust than context-independent sensitization. However, some findings
      suggest that behavioural sensitization develops irrespective of context. In this
      study an attempt was made to dissociate the development of context-dependent
      nicotine sensitization from the onset of nicotine-conditioned locomotor
      stimulation. Seven days of daily nicotine administration (0.6 mg/kg, s.c.) paired
      with exposure to locomotor activity boxes produced stable and consistent
      behavioural sensitization, at which time no nicotine-induced conditioned
      locomotor stimulation could be demonstrated. However, after an additional two
      days of nicotine treatment, i.e. on day 9, nicotine-conditioned behavioural
      stimulation was observed. Our findings suggest that behavioural sensitization to
      nicotine appears to reach a plateau before induction of nicotine-conditioned
      locomotor stimulation.

PMID- 15474647
TI  - Serotonin type 3 receptors stimulate offensive aggression in Syrian hamsters.
AB  - Hamsters repeatedly exposed to cocaine during adolescence display high levels of
      offensive aggression compared to saline-treated littermates. The escalated
      offensive phenotype observed in adolescent cocaine-treated animals is modulated
      by serotonin (5-HT) signaling and can be suppressed by inhibiting 5-HT type 3
      receptors, suggesting that these receptors might play an important role in the
      aggression-stimulating effects of adolescent cocaine exposure. The current study
      examined this hypothesis and extended earlier studies investigating the
      relationship between 5HT(3) receptor neural signaling and the offensive response
      patterns of aggressive, adolescent cocaine-treated animals compared to non
      aggressive, saline-treated littermates. Adolescent cocaine-treated hamsters and
      saline-treated littermates were tested for offensive aggression after the
      administration of either the 5-HT(3) antagonist 3-tropanylindole-3-carboxylate
      methiodide (tropisetron) or the 5-HT(3) agonist 1-(m-chlorophenyl)-biguanide
      hydrochloride (mCPBG). Tropisetron significantly reduced the high levels of
      offensive responding observed in adolescent cocaine-treated animals, whereas
      treatment with the 5-HT(3) receptor agonist mCPBG failed to affect the escalated
      offensive response. Conversely, tropisetron failed to affect very low, baseline
      levels of aggressive responding seen in adolescent saline-treated animals, while
      5-HT(3) receptor activation via mCPBG triggered highly escalated levels of
      offensive aggression in these animals. Together, these data support a stimulatory
      role for 5-HT(3) neural signaling in offensive aggression.

PMID- 15474648
TI  - Mesencephalic substrate of reward: lesion effects.
AB  - Psychophysical studies suggest that reward-relevant neurons in the posterior
      mesencephalon (PM) form a caudal extension of the axonal pathway that mediates
      the rewarding effectiveness of electrical stimulation of the medial forebrain
      bundle. The present study sought to further characterize the reward-relevant
      functional link between these two regions by assessing changes to the rewarding
      effectiveness of caudal medial forebrain bundle stimulation (ventral tegmental
      area, VTA) subsequent to electrolytic lesions of different PM sites. A total of
      13 rats were tested, 11 of these at bilateral VTA stimulation sites. Overall,
      rewarding effectiveness was reduced in five rats and pontentiated in four. The
      presence and magnitude of the effects were site-, current- and time-dependent,
      and ranged from 0.1 to 0.4 log(10) unit shifts in reward magnitude, with most
      effects falling below 0.3 log(10) units. Generally, these effects became apparent
      approximately two weeks after the lesion. In addition to these effects, PM
      lesions placed on or close to the midline also produced small transient
      reductions in rewarding effectiveness immediately after the lesion, an effect
      that disappeared within three days. Conversely, lateral PM lesions were
      associated either with no immediate effects or with small transient potentiations
      of reward. The finding that lesions of the PM placed on the midline, just off the
      midline or laterally all altered the rewarding effectiveness of VTA stimulation
      suggests that the reward-relevant circuitry is distributed diffusely throughout
      the PM.

PMID- 15474649
TI  - Multidimensional structure of anxiety-related behavior in early-weaned rats.
AB  - Early environmental stimuli affect various aspects of physical and behavioral
      development. Weaning is one of the most important events in the early stage of
      life, and recently we have found that precocious weaning augments anxiety and
      aggressiveness in mice. Here, we report the presence of virtually identical
      phenomena in rats. To understand the multidimensional structure of anxiety
      related behavior, the influence of early weaning upon behavior in adulthood was
      investigated using three behavioral tests: the elevated plus-maze test, the hole
      board test and the open-field test. Two groups of rats were prepared. One was
      weaned from the dam at 16 days of age (early-weaned group) and the other at 30
      days (normally weaned group) as a control. Both groups were subjected to the
      three tests at 8-10 weeks of age. The elevated plus-maze test revealed lower
      frequency of entry to and shorter duration of stay in the open arms in the early
      weaned animals. In the hole-board test, the early-weaned rats showed lower
      frequency and shorter duration of head dipping into the holes. And in the open
      field test, the early-weaned rats tended to stay at the central square for a
      shorter period and to defecate more frequently. The behavioral parameters of the
      three tests were combined and subjected to principal component analysis (PCA).
      The factorial scores for six extracted factors were compared between the early
      weaned and normally weaned groups, and it was revealed that the early-weaned rats
      had a lower score in Factor 1 (non-anxious exploration) and Factor 5 (risk
      assessment behavior). Taken together, these results suggest that the time of
      weaning had a considerable impact on behavioral development, particularly with
      respect to anxiety-related behaviors.

PMID- 15474650
TI  - Effects of L-DOPA on aggressive behavior and central monoaminergic activity in
      the lizard Anolis carolinensis, using a new method for drug delivery.
AB  - The dopamine (DA) precursor, L-DOPA (500 microg), was injected into living
      crickets, which were ingested (one each) by adult male Anolis carolinensis. This
      method of delivery elevated plasma L-DOPA and DA concentrations by approximately
      1000-fold. In contrast, plasma epinephrine (Epi) and norepinephrine (NE) were not
      influenced by L-DOPA treatment, although they were elevated following the
      consumption of the cricket. Lizards that ingested L-DOPA treated crickets had
      elevated L-DOPA in all brain regions measured, with DA and/or DOPAC also
      increased significantly in most brain regions studied. Despite increased DA
      levels in the striatum and nucleus accumbens as a response to L-DOPA, the
      treatment had no influence on general motor activity. Central serotonin, NE, and
      Epi systems were not affected in any brain region by oral L-DOPA treatment. In
      addition, aggression was inhibited by this dose of L-DOPA, even though there was
      no effect on serotonergic systems. This is surprising because controlling
      aggressive behavior is usually considered the province of serotonergic activity.
      Aggression was measured before and after treatment, and while saline-treated
      lizards retained the full vigor of aggressive activity, those fed a cricket
      injected with L-DOPA were only one-third as aggressive after treatment. As L-DOPA
      treatment did not affect general motor activity, the effect appears to be
      directly associated with aggression. This is supported by the observation that L
      DOPA treatment delayed latency to eyespot darkening, which predicts the latency
      to aggression.

PMID- 15474651
TI  - Whole-body exposure to 2.45 GHz electromagnetic fields does not alter anxiety
      responses in rats: a plus-maze study including test validation.
AB  - In a first phase of this investigation, a validation of our elevated plus-maze
      apparatus was performed in male Sprague-Dawley rats by testing anxiety response
      at various ambient light intensities (200, 30, 10 and 2.5 lux), as well as the
      effects of diazepam treatment (0.5 and 1.0 mg/kg, i.p. at 30 lux). Anxiety
      responses were found to decrease with decreasing light intensity and to be
      attenuated by diazepam treatment. Subsequently, a separate set of rats was
      exposed to 2.45 GHz EMFs (2 micros pulse width, 500 pulses per second, whole-body
      and time averaged of SAR 0.6 W/kg +/-2 dB, brain-averaged SAR of 0.9 W/kg +/-3
      dB) for 45 min to assess whether EMF exposure altered anxiety responses in the
      same apparatus. As we made no a priori hypothesis on whether the effects would be
      anxiogenic or anxiolytic, part of the rats were tested under an ambient light
      intensity of 2.5 lux, the other one being tested at 30 lux. The low intensity
      level set the behavioural baseline for the detection of anxiogenic effects, while
      the higher one corresponded to the detection of anxiolytic effects. Sham-exposed
      and naive rats were used as controls. Whatever light intensity was used, EMF
      exposure failed to induce any significant effect on anxiety responses in the plus
      maze. The present experiment demonstrates that exposure to EMFs, which was
      previously found to increase the number of benzodiazepine receptors in the rat
      cortex [Lai H, Carino MA, Horita A, Guy AW. Single vs. repeated microwave
      exposure: effects on benzodiazepine receptors in the brain of the rat.
      Bioelectromagnetics 1992;13(1):57-66], does not alter anxiety responses assessed
      in the elevated plus maze.

PMID- 15474652
TI  - Inhibition of morphine analgesia by LPS: role of opioid and NMDA receptors and
      spinal glia.
AB  - Intraperitoneal (i.p.) injection of toxins, such as the bacterial endotoxin
      lipopolysaccharide (LPS), is associated with a well-characterized increase in
      sensitivity to painful stimuli (hyperalgesia) [Watkins LR, Maier SF, Goehler LE.
      Immune activation: the role of pro-inflammatory cytokines in inflammation,
      illness responses and pathological pain states. Pain 1995;63:289-302. [53]] and a
      longer-lasting reduction in opioid analgesia (anti-analgesia) when pain
      sensitivity returns to basal levels [Johnston IN, Westbrook RF. Acute and
      conditioned sickness reduces morphine analgesia. Behav Brain Res 2003;142:89-97].
      Here we show that this inhibition of morphine analgesia 24 h after a single i.p.
      injection of LPS involves mechanisms that contribute to illness-induced
      hyperalgesia and the development of analgesic tolerance to morphine.
      Specifically, morphine analgesia was restored if LPS was preceded by systemic
      administration of a non-competitive NMDA receptor antagonist (MK-801), spinal
      infusion of a glial metabolic inhibitor (fluorocitrate), or
      intracerebroventricular microinjection of an opioid receptor antagonist
      (naloxone). Morphine analgesia was also restored if MK-801 was administered after
      LPS. These results demonstrate that LPS recruits similar, if not the same
      mechanisms that reduce morphine tolerance following opiate administration:
      namely, stimulation of opioid and NMDA receptors and recruitment of spinal glia.

PMID- 15474653
TI  - Effect of cholinergic medication, before and after focal photothrombotic ischemic
      cortical injury, on histological and functional outcome in aged and young adult
      rats.
AB  - The present study evaluated the effect of galanthamine, a selective competitive
      cholinesterase inhibitor, on histological and functional outcome after
      experimental stroke in rats. Cholinesterase inhibitors are commonly used as
      cognitive enhancers for dementia in aged people, including those who may sustain
      ischemic attacks. Young adult (5 months) and aged (24 months) rats were treated
      with saline or galanthamine at a dose of 2.5 mg/kg (i.p., once a day). Drug
      treatment started 4 days before focal cortical photothrombosis (Rose Bengal, 20
      mg/kg) and continued for 21 days thereafter. Sensorimotor recovery was assessed
      by a new beam-walking test and spatial learning by the Morris water-maze over a 3
      week follow-up period. Infarct volumes were measured from nitroblue tetrazolium
      stained sections at the end of follow-up. Infarct volumes in the cortex were
      similar in ischemic controls and ischemic rats treated with galanthamine. In the
      beam-walking test, there was a transient impairment forelimb function and a
      permanent impairment in hindlimb after cortical infarct both in young adult and
      aged rats. Galanthamine treatment did not affect the sensorimotor recovery rate.
      Analysis of water-maze data did not reveal significant differences in length of
      path, escape latency, or swim speed between sham-operated, ischemic controls and
      ischemic rats treated with galanthamine. In conclusion, present findings suggest
      that the aging brain has considerable plastic capacity to maintain functioning
      after focal cerebral insults restricted to the motor cortex. Galanthamine is not
      beneficial with respect to the histological or functional outcome in rats
      subjected to cortical photothrombosis.

PMID- 15474654
TI  - Auditory training improves neural timing in the human brainstem.
AB  - The auditory brainstem response reflects neural encoding of the acoustic
      characteristic of a speech syllable with remarkable precision. Some children with
      learning impairments demonstrate abnormalities in this preconscious measure of
      neural encoding especially in background noise. This study investigated whether
      auditory training targeted to remediate perceptually-based learning problems
      would alter the neural brainstem encoding of the acoustic sound structure of
      speech in such children. Nine subjects, clinically diagnosed with a language
      based learning problem (e.g., dyslexia), worked with auditory perceptual training
      software. Prior to beginning and within three months after completing the
      training program, brainstem responses to the syllable /da/ were recorded in quiet
      and background noise. Subjects underwent additional auditory neurophysiological,
      perceptual, and cognitive testing. Ten control subjects, who did not participate
      in any remediation program, underwent the same battery of tests at time intervals
      equivalent to the trained subjects. Transient and sustained (frequency-following
      response) components of the brainstem response were evaluated. The primary
      pathway afferent volley -- neural events occurring earlier than 11 ms after
      stimulus onset -- did not demonstrate plasticity. However, quiet-to-noise inter
      response correlations of the sustained response ( approximately 11-50 ms)
      increased significantly in the trained children, reflecting improved stimulus
      encoding precision, whereas control subjects did not exhibit this change. Thus,
      auditory training can alter the preconscious neural encoding of complex sounds by
      improving neural synchrony in the auditory brainstem. Additionally, several
      measures of brainstem response timing were related to changes in cortical
      physiology, as well as perceptual, academic, and cognitive measures from pre- to
      post-training.

PMID- 15474655
TI  - Effect of repeated corticosterone injections and restraint stress on anxiety and
      depression-like behavior in male rats.
AB  - Repeated stress is an important risk factor for the development of depression.
      However, the mechanism by which stress influences depression is largely unknown,
      in part due to the fact that few animal models of repeated stress produce robust
      changes in depression-like behavior. The purpose of the present study was to
      characterize the effect of repeated corticosterone (CORT) injections and repeated
      restraint stress on anxiety and depression-like behavior in male rats. Rats
      received CORT injections (40 mg/kg, s.c.), vehicle injections, restraint stress
      (6 h/day), or handling once per day for 21 consecutive days prior to the
      behavioral testing. The rats were then tested for changes in fearful/anxious
      behavior in the open-field and social interaction tests and for depression-like
      behavior in the forced swim test. The repeated CORT injections had no significant
      effect on activity levels or anxiety in the open-field or social interaction
      tests. However, they did increase depression-like behaviors in the forced swim
      test. Repeated restraint stress had no significant effect on anxiety or
      depression-like behavior on any of the behavioral tests. These results suggest
      that repeated CORT injections warrant further investigation as an animal model to
      study the role of stress in depression.

PMID- 15474656
TI  - Odor detection of single chemicals and binary mixtures.
AB  - The investigation explored the olfactory detectability of two chemically and
      structurally similar esters, ethyl propanoate and ethyl heptanoate, presented
      singly and in mixtures. Initially, we measured concentration-detection (i.e.,
      psychometric) functions for the odor of ethyl propanoate and ethyl heptanoate
      presented singly. Using this information, we prepared binary mixtures of the two
      chemicals in varying complementary proportions and, also, selected concentrations
      of the single compounds, such that, if a rule of response-addition (i.e.,
      independence of detection) were to hold, the stimuli (mixed and single) should
      approximate equal detection. Next, we measured the actual detectability of these
      stimuli within the same experiment. The results were analyzed in terms of
      response-addition (or -additivity) and of dose-addition (or -additivity). The
      outcome revealed that at low levels of detectability the mixtures approximate
      response-addition, that is, independence of detection, whereas at high levels of
      detectability they approximate dose-addition. In the light of previous findings
      for the olfactory detection of the more dissimilar chemical pairs 1-butanol/2
      heptanone and butyl acetate/toluene, we conclude that the described outcome
      generalizes across a variety of chemical pairs.

PMID- 15474657
TI  - Skilled reaching impairments from the lateral frontal cortex component of middle
      cerebral artery stroke: a qualitative and quantitative comparison to focal motor
      cortex lesions in rats.
AB  - The classical approach to investigating brain contributions to behavior has been
      to localize function to a region. In clinical investigations, however, injury is
      frequently multifocal, raising the question of how individual brain regions
      contribute to a resulting behavioral syndrome. For example, middle cerebral
      artery (MCA) ischemia in humans can concurrently damage a number of cortical and
      subcortical areas and the same areas are damaged in rat models of MCA stroke. In
      the rat, MCA occlusion produces severe motor deficits, but the cortical area of
      damage is the lateral neocortex, sparing motor cortex. This anatomical finding
      raises the question of whether the rat lateral neocortex contributes to MCA
      related motor impairments, a question that was investigated in the present study.
      Rats received unilateral neocortical lesions via electrocoagulation of the MCA
      and were compared to rats with standard motor cortex lesions produced by
      devascaulrization of the overlaying blood vessels. The MCA group was as impaired
      as the motor cortex group in skilled reaching movements as assessed by
      quantitative measures of the contralateral-to-lesion forelimb in a single pellet
      task and in a tray-reaching task. Although there was improvement in success
      scores over a 2-week period in both groups, the groups were characterized by
      distinctive and enduring qualitative impairments. The motor cortex deficit was
      exemplified by use of trunk musculature and head movements to assist the reaching
      limb while the MCA impairment included sensory abnormalities. The results are
      discussed in relation to the contribution of lateral frontal cortex injury to MCA
      stroke sensorimotor syndromes.

PMID- 15474658
TI  - Pre- or post-training administration of the NMDA receptor blocker MK-801 impairs
      object recognition memory in rats.
AB  - The aim of the present study was to investigate the effects of NMDA receptor
      blockade on formation of object recognition memory. In the first experiment,
      adult Wistar rats were given an intraperitoneal injection of saline or the NMDA
      receptor antagonist [(+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclo-hepten-5,10
      imine-maleate] (MK-801) (0.001, 0.01, or 0.1 mg/kg) 20 min prior to training in a
      novel object recognition task. In the second experiment, saline or MK-801 (0.1
      mg/kg) were given immediately after training. Memory retention was tested 1.5 and
      24 h after training. MK-801 impaired both short- and long-term retention of
      object recognition memory when given either before or after training. The results
      suggest that NMDA receptor activation is necessary for formation of object
      recognition memory.

PMID- 15474659
TI  - The effect of orbital prefrontal cortex lesions on performance on a progressive
      ratio schedule: implications for models of inter-temporal choice.
AB  - In a previous experiment [Kheramin S, Body S, Mobini S, Ho M-Y, Velazquez
      Martinez DN, Bradshaw CM, et al. Effects of quinolinic acid-induced lesions of
      the orbital prefrontal cortex on inter-temporal choice: a quantitative analysis.
      Psychopharmacology 2002;165: 9-17], destruction of the orbital prefrontal cortex
      (OPFC) in rats altered choice between two delayed food reinforcers, enhancing
      preference for the larger reinforcer. Theoretical analysis based on a
      quantitative model of inter-temporal choice [Ho M-Y, Mobini S, Chiang T-J,
      Bradshaw CM, Szabadi E. Theory and method in the quantitative analysis of
      'impulsive choice' behaviour: implications for psychopharmacology.
      Psychopharmacology 1999;146:362-72] indicated that the lesion had increased the
      relative value of the larger of the two reinforcers due to a general reduction of
      absolute reinforcer value. The present experiment tested this hypothesis using a
      reinforcement schedule that did not entail either explicit choice or delayed
      reinforcement. Ten rats received quinolinic acid-induced lesions of the OPFC, and
      ten rats received sham lesions. The rats were trained under a progressive-ratio
      schedule of food reinforcement for 60 daily sessions. Response rates in
      successive ratios were a bitonic (inverted-U) function of ratio size. Analysis of
      the data using a three-parameter equation derived from a quantitative model of
      ratio schedule performance [Killeen PR. Mathematical principles of reinforcement.
      Behav. Brain Sci. 1994;17:105-72] revealed that the parameter specifying
      hypothetical reinforcer value was significantly lower in the OPFC-lesioned group
      than in the sham-lesioned group, consistent with the hypothesis that destruction
      of the OPFC resulted in devaluation of the food reinforcer.

PMID- 15474660
TI  - Correlations between behaviours in the elevated plus-maze and sensitivity to
      unpredictable subchronic mild stress: evidence from inbred strains of mice.
AB  - This study aimed at investigating the relationship between anxiety-like and
      depressive-like behaviour in mice. Therefore, we assessed the behaviour of mice
      from eight different strains (FVB/NA, BALB/c, C57BL/6, DBA/2, 129/Sv, C3H/He, CBA
      and BA) confronted first to anxiety models (the elevated plus-maze and the free
      exploratory test) and then to tests of depressive-like behaviours (forced swim
      test and unpredictable subchronic mild stress). In the forced swim test, mice
      from the DBA/2, the BA and the C3H/He strains displayed higher immobility than
      mice from the 129/Sv, the BALB/c, the C57BL/6 and the CBA strains. In the
      subchronic mild stress, mice from the C57BL/6 and the CBA strains displayed low
      sensitivity when compared with mice from all the others strains. A stepwise
      multiple regression analysis suggests that behaviour in the elevated plus-maze is
      associated with the time of immobility in the forced swim test (20%) and with the
      susceptibility to the unpredictable subchronic stress procedure (31%). The
      behaviour in the free exploratory paradigm is slightly associated with behaviours
      in the two tests of depression. These results suggest that anxiety may be a
      factor contributing, among others, to the susceptibility to depressive-like
      behaviours.

PMID- 15474661
TI  - The biology of non-small-cell lung cancer: identifying new targets for rational
      therapy.
AB  - Lung cancer, and in particular non-small-cell lung cancer (NSCLC), remains the
      leading cause of cancer death throughout the world. Almost three decades ago, the
      major concern was to identify whether cisplatin or cisplatin-based chemotherapy
      enhanced survival in metastatic NSCLC, and whether any survival benefit
      compensated for cisplatin-related toxicity. Over the last 10 years, significant
      advances have been achieved in molecular biology, including the identification of
      critical genes related to the pathogenesis of NSCLC, which have formed the basis
      for new targeted therapeutic approaches. These new approaches include novel
      agents against established chemotherapeutic targets such as thymidylate
      synthetase as well as agents that inhibit novel targets such as growth factor
      receptors and proteins important in angiogenesis. With the advent of genomic
      technologies that can identify patterns of gene expression, the hope is that
      therapy will be tailored to the genetic pattern of the patients's tumor, and
      individualized treatments that minimize toxicity and maximize efficacy can be
      developed.

PMID- 15474662
TI  - Role of epoetin in the management of anaemia in patients with lung cancer.
AB  - Lung cancer is associated with the one of the highest rates of anaemia of all
      solid tumours. Anaemia has a negative impact on treatment outcome and overall
      survival of patients with cancer and also affects their quality of life.
      Recombinant human erythropoietin (epoetin) provides an effective and safe
      treatment of cancer-related anaemia without the risks associated with red blood
      cell transfusion. Epoetin therapy increases haemoglobin levels, reduces the need
      for blood transfusions and improves the quality of life of patients with anaemia
      and lung cancer. Epoetin beta is also effective for preventing the development of
      anaemia and decreasing transfusion requirements when administered with
      concomitant platinum-based chemotherapy. In addition, preliminary evidence
      suggests that treatment with erythropoietic agents may improve survival of lung
      cancer patients, although this needs to be verified in prospective clinical
      trials specifically designed to evaluate survival. Therefore, early initiation of
      epoetin beta to prevent chemotherapy-associated anaemia may represent the best
      strategy for patients with lung cancer being treated with chemotherapy.

PMID- 15474663
TI  - Lung cancer mortality predictions for Ireland 2001-2015 and current trends in
      North Western Europe.
AB  - PURPOSE AND METHODOLOGY: Poisson regression models of Irish lung cancer mortality
      data for the years 1954-2000 were used to predict European age standardized
      mortality rates (EASMRs) and numbers of deaths for the period 2001-2015.
      Predictions for the whole population and for the age group 0-64 years were the
      main focus of this analysis. The models employed in this analysis were written
      for the STATA 6.0 STATISTICAL PACKAGE FOR WINDOWS. Linear models were applied, in
      general, to upward trends and log-linear models to downward trends. RESULTS: For
      males of all ages, EASMRs are expected to fall significantly from 59.7 per
      100,000 person years (100,000 PY(-1)) in 2000 to 47.2 in the period 2011-2015.
      Female EASMRs are expected to fall from 28.3 100,000 PY(-1) in 2000 to 27.8 in
      2011-2015. The EASMR for males under 65 years of age is predicted to continue its
      decline from 20.6 100,000 PY(-1) in 2000 to 11.7 in 2011-2015. The rate for
      females in this same age group is predicted to decline from 10.7 100,000 PY(-1)
      in 2000 to 7.0 in 2001-2015. Recent lung cancer trends In Ireland were also
      compared to other countries in North Western Europe.

PMID- 15474664
TI  - Gender difference in human papillomarvirus infection for non-small cell lung
      cancer in Taiwan.
AB  - Our previous reports have indicated that high risk human papillomarvirus (HPV)
      16/18 were much more frequently detected in lung tumors of female patients as
      compared to that of male patients and HPV 16/18 in lung tumors were evolutionally
      correlated with those in blood circulation. In the other hand, it is well known
      that HPV 6/11 are frequently associated with upper aerodigestive and respiratory
      diseases. HPV 6/11 DNA were detected in lung tumors by nested PCR and in situ
      hybridization to investigate if any difference in prevalent types of HPV exists
      between genders. Our data showed that HPV 6 infection was detected in 28.4% (40
      of 141) lung tumors, which was significantly higher than that in non-cancer
      controls (1.7%, 1 of 60; P < 0.0001), however, such high prevalence was not
      observed for HPV 11. Among studied clinico-pathological parameters, HPV 6
      infection was significantly related with gender (P = 0.002) and smoking status (P
      = 0.014). After being stratified by gender and smoking status, HPV 6 infection
      rate in lung tumors of non-smoking male patients was much higher than that in non
      smoking female patients (33.3% versus 11.1%; P = 0.023), but no difference
      between smoking and non-smoking male patients (38.1% versus 33.3%). With
      adjustments for age, tumor type, and tumor stage, smoking male lung cancer
      patients had a much higher OR value (OR, 7.35; 95%CI, 2.11-25.58) for HPV 6
      infection compared with 3.93 (95% CI, 1.17-13.12) of non-smoking male patients.
      Moreover, a higher prevalence of HPV 6 was detected in lung tumors of smoking
      male patients with early tumor stage than those with advanced stages (P = 0.008),
      but not in non-smoking male and female patients. A higher prevalence of HPV 6 in
      male lung cancer patients, as compared with female lung cancer patients,
      indicating not only different HPV infection routes for different genders, but
      also that HPV 6 infections may act as a prospective early risk marker of lung
      cancer for smoking male patients in Taiwan.

PMID- 15474665
TI  - Histone deacetylase 1 mRNA expression in lung cancer.
AB  - Histone deacetylases (HDACs) play a crucial role in tumorigenesis, however, the
      expression status of HDACs in lung cancer tissues has not been reported. We have
      investigated that HIDAC 1 mRNA levels and other clinico-pathological data,
      including MTA 1 mRNA expression in lung cancer. The study included 102 lung
      cancer cases. The HDAC1 mRNA levels were quantified by real time reverse
      transcription-polymerase chain reaction (RT-PCR) using LightCycler (Roche
      Molecular Biochemicals, Mannheim, Germany). The HDAC1/GAPDH mRNA levels were not
      significantly different in tumor tissues from lung cancer (30.654 +/- 33.047) and
      adjacent non-malignant lung tissues (18.953 +/- 56.176 , P = 0.1827). No
      significant difference in HDAC1/GAPDH mRNA levels was found among age, gender,
      and lymph node metastasis. The HDAC1/GAPDH mRNA levels were significantly higher
      in stage III or IV lung cancer (50.929 +/- 120.433) than in stage I lung cancer
      (11.430 +/- 25.611, P = 0.0472). HDAC1/GAPDH mRNA levels were significantly
      higher in T3 or T4 lung carcinoma (54.326 +/- 127.018) than in T1 or T2 lung
      cancers (14.790 +/- 48.670, P = 0.1601). HDAC1/GAPDH mRNA levels were correlated
      with MTA1/GAPDH mRNA levels (y = 0.0106x + 2.5827 , P = 0.0352 ). HDAC1/GAPDH
      mRNA levels were also correlated with HDAC1 protein (P = 0.0484) expression by
      immunohistochemistry. Using the LightCycler RT-PCR assay, the HDAC1 gene
      expression might correlate with progression of lung cancers. However, further
      studies are needed to confirm the impact of HDAC1 for the molecular target of the
      lung cancer.

PMID- 15474666
TI  - Susceptibility of mesothelioma cell lines to adeno-associated virus 2 vector
      based suicide gene therapy.
AB  - Although great efforts have been made to improve conventional therapy for diffuse
      malignant pleural mesothelioma, the median survival time of the patients after
      appearance of clinical symptoms remains poor. Due to confinement of the primary
      tumor to the pleural space, locoregional approaches are attractive strategies to
      improve the clinical outcome. In this context locoregional gene therapy using the
      recombinant adeno-associated virus 2 (rAAV-2) may be a new approach. Vectors were
      constructed containing a fusion gene, consisting of the Herpes simplex virus
      thymidine kinase (HSV-TK) and the green fluorescent protein (GFP) genes; the
      former serving as suicide gene by converting the prodrug ganciclovir (GCV) into a
      toxic agent, thereby killing infected cells. Among a number of different tumor
      cell lines, rAAV-2 achieved high GFP expression levels in three mesothelioma cell
      lines (H-Meso-1, MSTO-211H, NCI-H28). A variety of rAAV-2-constructs containing
      different promoters were tested. The vector with the elongation factor-1alpha (EF
      1alpha) promoter showed the highest expression rates. Expression could be further
      increased by addition of the tyrosine kinase inhibitor genistein. Using the rAAV
      2-based suicide system, a nearly complete eradication of transduced and GCV
      treated mesothelioma cells was observed. rAAV-2-based suicide gene therapy may be
      a new approach for locoregional treatment of mesothelioma.

PMID- 15474667
TI  - Biological features of bronchial squamous dysplasia followed up by
      autofluorescence bronchoscopy.
AB  - Some dysplasias in the bronchial epithelium are thought to be precancerous
      lesions that can develop into squamous cell carcinomas. In this investigation, we
      assessed the biological behavior of bronchial squamous dysplasia in order to
      define which dysplasias have the potential to progress to squamous cell
      carcinoma. Using autofluorescence bronchoscopy, we followed up periodically
      localized dysplasias and examined for correlation between histological outcome
      and smoking status during the follow-up period, telomerase activity, Ki-67
      labeling index, and p53 immunoreactivity of initial biopsy specimens. Ninety-nine
      dysplasias from 50 participants mainly with sputum cytology suspicious or
      positive for malignancy were followed up. Of 99 dysplasias, 3 dysplasias
      progressed to squamous cell carcinoma, 41 dysplasias remained as dysplasia, 6
      dysplasias changed to metaplasia, 14 dysplasias changed to hyperplasia, and 35
      dysplasias regressed to bronchitis or normal bronchial epithelium. There were no
      significant associations between histological outcome and smoking status. Mean
      initial telomerase activity and Ki-67 labeling index values in the dysplasias
      increased in proportion to the severity of the histological outcome at the second
      biopsy. There was also a significant difference between p53-positive and p53
      negative dysplasia in terms of histological outcome at the second biopsy. Our
      results suggested that dysplasias with high telomerase activity, increased Ki-67
      labeling index, and p53-positivity tended to remain as dysplasia and might have
      the potential to progress to squamous cell carcinoma. Patients with dysplastic
      lesions with these characteristics should be carefully followed up.

PMID- 15474668
TI  - Validating the prognostic value of marker genes derived from a non-small cell
      lung cancer microarray study.
AB  - We previously reported that our cDNA microarray analysis of primary non-small
      cell lung carcinoma (NSCLC) could predict for patients at increased risk of
      cancer recurrence. From the result of this analysis, we selected 11 genes that
      were considered candidate prognostic marker genes and used the realtime reverse
      transcription polymerase chain reaction (RT-PCR) to investigate their expression
      in the same set of NSCLC cases used in the microarray study. Cluster analysis of
      the realtime RT-PCR data separated these patients into two groups with
      significantly different disease-free survivals (log-rank test, P < 0.017). In
      contrast, cluster analysis failed to confirm the prognostic significance of the
      realtime RT-PCR results for these 11 genes in a validation series of 92 NSCLC
      cases. In univariate analysis, hypoxia inducible factor 1alpha, Rho-GDP
      dissociation inhibitor (GDI) alpha (RhoGDI) and Citron/rho-interacting serine
      threonine kinase 21 (Citron K21) were significant prognostic factors for disease
      free survival in the entire cohort of 130 NSCLC patients, but none were
      significant in multivariate analysis. The results demonstrate that the prognostic
      significance of microarray (SAM) results can be partially validated using
      realtime RT-PCR, but secondary validation using larger and independent series of
      tumors is necessary to identify true prognostic marker genes.

PMID- 15474669
TI  - The significance of serum active matrix metalloproteinase-9 in patients with non
      small cell lung cancer.
AB  - Matrix metalloproteinase-9 (MMP-9) plays an essential role for metastasis. The
      purpose of this study is to investigate the significance of active MMP-9
      quantified in serum of patients with non-small cell lung cancer.
      Immunohistochemical staining of the primary tumors was also performed to analyze
      how much the secretion of MMP-9 from cancer cells influences the concentration of
      MMP-9 in serum. The preoperative sera of 39 patients with NSCLC, who underwent an
      operation at our institution from 1996 to 1999, were taken before the operation.
      Forty-three samples of sera were drawn postoperatively. Of these 43 samples, 16
      sera were taken from patients who suffered with recurrence, 27 sera were taken
      from patients who did not suffer with recurrence. The serum level of active MMP-9
      of preoperative state was 24.3 +/- 21.2 ng/ml, which was higher than that of
      control was 14.6 +/- 18.8 ng/ml, but no significance was recognized statistically
      between them (P = 0.0666). The immunoreactivity of MMP-9 was not correlated
      statistically with serum level of total MMP-9 and active MMP-9. The activity
      ratio of non-recurrent group was also a lower level than that of recurrent group
      (P = 0.0082). In conclusion, our results suggest that the concentration of serum
      active MMP-9 has a possibility of being an available marker to detect a recurrent
      disease. Our findings strongly suggest that measuring the activity ratio of serum
      MMP-9 appears to be a potentially useful tumor maker.

PMID- 15474670
TI  - Study design considerations in clinical outcome research of lung cancer using
      microarray analysis.
AB  - BACKGROUND: Prognosis following a diagnosis of primary lung cancer is very poor
      and varies significantly even after adjusting for known predictors. Inherent and
      acquired gene alterations could cause failure in lung cancer treatment and
      patient survival. To search for potential molecular markers with significant and
      independent predictive value in lung cancer survival, we applied oligo-nucleotide
      microarray analysis, along with patients' phenotypic profile, in a case-control
      study. The focus of this report is on the methodology used in the identification
      of potential genes as prognostic factors. METHODS: Selected from 304 patients at
      Mayo Clinic, 18 stage I squamous cell lung cancer patients who died within 2
      years (high-aggressive) or lived beyond 5 years (low-aggressive) were included in
      this study. Both a one-to-one matched design (paired) and a two-group design
      (grouped) were utilized. Matching variables were age, gender, tumor size and
      grade, smoking status, and treatment. Two-GeneChip-array sets from Affymetrix (HG
      U133) were used. We applied multiple analytic approaches including Dchip (Harvard
      University), SAM (Stanford University), ArrayTools (US National Cancer
      Institute), and MAS5 (Affymetrix); and integrated multiple results to generate
      the final candidate genes for further investigation. We evaluated the consistency
      across the methods and the effects of matched versus grouped design on the
      results. RESULTS: Using the same pre-processed data under the same criteria for
      type I error and fold-change in expression intensity, results are 94-100%
      concordant in the list of significant genes by Dchip and by ArrayTools, and 53%
      concordant between the paired and the grouped analysis. If using differently pre
      processed data, the concordance rate is under 6% even by the same analytic tool.
      Combining results from all analyses, we found 23 potentially important genes that
      may distinguish the high- versus low-aggressive squamous cell tumors of the lung.
      CONCLUSION: Given the generally low consistency of results across analytic
      algorithms and study design, poor agreement is expected from different
      investigators reporting candidate genes for the same endpoint. A well-designed
      study with a carefully planned analytic strategy is critical. We are in the
      process of validating the 23 preliminary candidate genes found from this study
      among independent yet comparable cases.

PMID- 15474671
TI  - The beneficial effects of specialist thoracic surgery on the resection rate for
      non-small-cell lung cancer.
AB  - We aimed to evaluate the effect of the appointment of a dedicated specialist
      thoracic surgeon on surgical practice for lung cancer previously served by cardio
      thoracic surgeons. Outcomes were compared for the 240 patients undergoing
      surgical resection for lung cancer in two distinct 3-year periods: Group A: 65
      patients, 1994-1996 (pre-specialist); Group B: 175 patients, 1997-1999 (post
      specialist). The changes implemented resulted in a significant increase in
      resection rate (from 12.2 to 23.4%, P < 0.001), operations in the elderly (over
      75 years) and extended resections. There were no significant differences in stage
      distribution, in-hospital mortality or stage-specific survival after surgery.
      Lung cancer surgery provided by specialists within a multidisciplinary team
      resulted in increased surgical resection rates without compromising outcome. Our
      results strengthen the case for disease-specific specialists in the treatment of
      lung cancer.

PMID- 15474672
TI  - Influence of age, comorbidity and performance status on the choice of treatment
      for patients with non-small cell lung cancer; results of a population-based
      study.
AB  - BACKGROUND: In the Netherlands in 1997, 43% of patients with newly diagnosed lung
      cancer were over 70. Large age-specific differences in treatment exist. We
      examined whether age, comorbidity, performance status and pulmonary function
      influenced treatment. PATIENTS AND METHODS: Data on patients with newly diagnosed
      non-small cell lung cancer (N = 803) were obtained: comorbidity, performance
      status, pulmonary function (FEV1) and initial treatment. Age-specific differences
      in treatment according to the guidelines were examined. Odds ratios were
      calculated by means of logistic regression analyses. RESULTS: 82% with stage I or
      II disease received treatment according to the guidelines; this applied to 48%
      with stage IIIA disease and to 54% with stage IIIB disease. For all stages, this
      proportion decreased with increasing age. In stage IV disease, 36% did not
      receive any treatment; this applied to 52% of the elderly patients (75+ years).
      Multivariate analyses showed associations between comorbidity and treatment
      choice, but none with performance status. Age of 75+ years appeared to be the
      most important factor for not receiving treatment according to guidelines.
      CONCLUSION: A substantial proportion of elderly patients with non-small cell lung
      cancer did not receive standard treatment. Performance status and comorbidity
      seldom formed the underlying reason. Calendar rather than biological age seemed
      to play the most important role in choice of treatment for patients with non
      small cell lung cancer.

PMID- 15474673
TI  - Retrospective analysis of the predictive factors associated with the response and
      survival benefit of gefitinib in patients with advanced non-small-cell lung
      cancer.
AB  - BACKGROUND: The purpose of the study was to identify the potential predictive
      features associated with the response and survival benefit of gefitinib
      administration. We have retrospectively reviewed data of all patients who
      received a single regimen of gefitinib in our institution from August 1998 until
      July 2003. METHODS: Overall 101 patients with non-small-cell lung cancer (NSCLC)
      who have received a single use of gefitinib were analyzed. Potential factors
      associated with the response of gefitinib included smoking index, gender,
      histology, performance status (PS), number of pre-treatments, age and stage.
      Univariate analysis was performed for these strata by Fisher's exact test and
      multivariate analysis was then performed using the logistic regression model.
      RESULTS: The overall response rate was 19.8%. Univariate analysis revealed that
      significant predictive factors were associated with the response for
      'adenocarcinoma', 'female', 'good PS' (0-l) and 'non-smoker' categories.
      Multivariate analysis limited the predictive factors associated with the response
      for 'female' (P = 0.0032), 'good PS' (P < 0.02) and 'non-smoker' (P = 0.0417). In
      survival analyses, 'female' (P < 0.005), 'good PS' (P < 0.0001), and a low level
      of the smoking index (P < 0.05) indicated significantly prolonged survival.
      Response and survival data in elderly patients were equivalent to those in
      younger patients. Adverse events (AEs) were generally mild and were almost always
      skin reactions and diarrhea. Interstitial lung disease (ILD) occurred in 4% of
      the group under observation. CONCLUSIONS: Gefitinib provided clinical benefit for
      the following factors 'female', 'good PS' and 'non-smoker'. A low smoking index
      is reported as a novel predictive prognostic factor following a single regimen of
      gefitinib.

PMID- 15474674
TI  - Effect of gefitinib ('Iressa', ZD1839) on brain metastases in patients with
      advanced non-small-cell lung cancer.
AB  - BACKGROUND: Gefitinib ('Iressa', ZD1839), an orally active epidermal growth
      factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI), has shown antitumor
      activity in refractory patients with non-small-cell lung cancer (NSCLC) in
      clinical trials. We have retrospectively analyzed the efficacy and tolerability
      of gefitinib in patients with advanced NSCLC treated at Okayama University
      Hospital. METHODS: We reviewed the clinical records of 57 patients with advanced
      NSCLC who had received 250 mg/day gefitinib at our hospital between November 2000
      and May 2003. Correlations between the sensitivity of brain metastases and
      extracranial disease following treatment with gefitinib were also investigated.
      RESULTS: Extracranial objective responses were observed in 15 (27%; 95%
      confidence interval 15.8-40.3%) patients. Fourteen out of 57 patients had brain
      metastases; six experienced objective responses (one complete response, CR and
      five partial responses, PR) and eight had stable disease (SD) in the brain. Seven
      out of 14 patients with brain metastases experienced objective responses in their
      extracranial tumors and, interestingly, objective responses in the brain were
      observed in six (86%) of these patients. Multivariate analysis found that
      advanced age (> or = 70 years) and the presence of brain metastases were
      associated with clinical response to gefitinib (P = 0.01 and 0.05, respectively),
      and that female patients were more likely to respond. Median survival and median
      duration of response were 9.1 and 7.7 months, respectively. The majority of
      adverse events (AEs) were mild and reversible skin and gastrointestinal
      disorders, with grade 3 adverse events observed in six (11%) patients.
      CONCLUSIONS: This retrospective analysis has found that gefitinib is effective
      and well tolerated in patients with refractory NSCLC, confirming previous phase
      II trial data. Interestingly, gefitinib appeared to be effective for brain
      metastases as well as extracranial tumors. Further prospective trials are
      warranted to evaluate the efficacy of gefitinib in elderly patients and in
      patients with brain metastases.

PMID- 15474675
TI  - Necessity of identifying the patterns of failure after concurrent
      radiochemotherapy part of a combined modality approach in patients with stage III
      non-small cell lung cancer [Sakai et al., Lung Cancer 2004;43:195-201].

PMID- 15474677
TI  - Neuromuscular weakness and collapse.

PMID- 15474678
TI  - Feline neuromuscular disorders.

PMID- 15474679
TI  - Inherited peripheral neuropathies in dogs and cats.

PMID- 15474680
TI  - Motor neuron disease: inherited and acquired.

PMID- 15474681
TI  - Malignant hyperthermia: a syndrome not a disease.

PMID- 15474682
TI  - Tremor, fasciculations, and movement disorders.

PMID- 15474683
TI  - Paraneoplastic neuromuscular disorders.

PMID- 15474684
TI  - Rhabdomyolysis, myoglobinuria, and necrotizing myopathies.

PMID- 15474685
TI  - Muscle pain, cramps and hypertonicity.

PMID- 15474686
TI  - Newly identified neuromuscular disorders.

PMID- 15474687
TI  - Therapeutic options for neuromuscular diseases.

PMID- 15474688
TI  - BNP or echocardiography for monitoring heart failure?

PMID- 15474689
TI  - Metabolic therapy for heart failure.

PMID- 15474690
TI  - Picotamide versus aspirin in diabetic patients with peripheral arterial disease:
      has David defeated Goliath?

PMID- 15474691
TI  - Cardiomyopathies: is it time for a molecular classification?
AB  - Primary myocardial diseases have always attracted the interest of the scientific
      community because of their obscure aetiopathogenesis. For years there was a
      confusion and controversy over their definition and classification. The 1995 WHO
      classification led to major advancements such as the introduction of a unified
      terminology, the official recognition of novel entities (arrhythmogenic right
      ventricular and idiopathic restrictive cardiomyopathies) and the definitive
      clarification that inflammatory heart disease has to be regarded as a
      cardiomyopathy. However, according to the new definition of cardiomyopathies as
      diseases of the myocardium associated with cardiac dysfunction, they should
      include not only forms with depressed contractility and impaired diastolic
      function, but also conduction and rhythm disturbances and enhanced
      arrhythmogenicity. Moreover, the recent development of molecular genetics, with
      the discovery of a genetic background in several forms previously defined of
      unknown origin, raises the need of a debate on a possible classification based on
      genomics.

PMID- 15474692
TI  - Primary hyperparathyroidism and heart disease--a review.
AB  - Primary hyperparathyroidism (pHPT), caused by solitary parathyroid adenomas in
      85% of cases and diffuse hyperplasia in most of the remaining cases, overproduces
      parathyroid hormone (PTH), which mobilizes calcium to the blood stream. Renal
      stones, osteoporosis and diffuse symptoms of hypercalcaemia, such as
      constipation, fatigue and weakness are well-known complications. However, in
      Western Europe and North America, patients with pHPT are nowadays usually
      discovered during an early, asymptomatic phase of the disease. It has been
      reported that patients suffering from symptomatic pHPT have increased mortality,
      mainly due to an overrepresentation of cardiovascular death. pHPT is reported to
      be associated with hypertension, disturbances in the renin-angiotensin
      aldosterone system, and structural and functional alterations in the vascular
      wall. Recently, studies have indicated an association between pHPT and heart
      disease, and studies in vitro have produced a number of theoretical approaches.
      An increased prevalence of cardiac structural abnormalities such as left
      ventricular hypertrophy (LVH) and valvular and myocardial calcification has been
      observed. Associations have been found between PTH and LVH, and between LVH and
      serum calcium. LV systolic function does not seem to be affected in patients with
      pHPT, whereas any influence on LV diastolic performance needs further evaluation.
      The aim of this review is to clarify the connection between pHPT and cardiac
      disease.

PMID- 15474693
TI  - Comparison of echocardiography and plasma B-type natriuretic peptide for
      monitoring the response to treatment in acute heart failure.
AB  - AIMS: Comparison of the value of echocardiography and B-type natriuretic peptide
      (BNP) in monitoring response to treatment in patients admitted for acute heart
      failure (HF). METHODS AND RESULTS: Ninety-five consecutive patients admitted with
      acute HF underwent bedside Doppler echocardiography and BNP measurements on
      admission, after 24 h of intravenous treatment, and at day 7. We then studied the
      association between the clinical status, the Doppler echocardiographic findings,
      the BNP measurements and subsequent 60-day adverse outcome (death, resuscitated
      cardiac arrest, urgent heart transplantation, readmission). On admission and
      during hospitalisation, relationships were found between plasma BNP and Doppler
      echocardiographic findings, and between their changes. During a 60 day follow-up,
      37 events occurred. Multivariable analysis taking into account clinical factors,
      Doppler echocardiography and BNP showed that the two best models to predict
      outcome were (1) early evaluation at day 2 (previous CHF treatment, dobutamine
      use, relative BNP change during first 24 h) and (2) late evaluation at day 7
      (previous CHF treatment, dobutamine use, BNP at day 7). Patients with a decrease
      in plasma BNP >10% at day 2, or with plasma BNP <300 pg/ml at day 7 had a better
      outcome than the others (19% versus 65% and 16% versus 72% events, respectively,
      p<0.0001). CONCLUSIONS: Serial BNP measurements during the treatment of acute HF
      provide incremental prognostic information over clinical presentation and
      repetitive echocardiographic examination.

PMID- 15474694
TI  - Combined endurance/resistance training reduces NT-proBNP levels in patients with
      chronic heart failure.
AB  - AIMS: This study was designed to evaluate the effects of combined
      endurance/resistance training on NT-proBNP levels in patients with chronic heart
      failure (CHF). The safety of resistive weight training for patients with CHF is
      questioned. Possible detrimental effects include an increase in ventricular
      diastolic pressure and secondary unfavourable remodelling. Circulating levels of
      the N-terminal fragment of brain natriuretic peptide (NT-proBNP) reflect left
      ventricular diastolic wall stress and are strongly related to mortality and
      treatment success in CHF. METHODS AND RESULTS: In this study, 27 consecutive
      patients with stable CHF and left ventricular ejection fraction (LVEF) <35% were
      enrolled in a 4 months non-randomized combined endurance/resistance training
      programme. Blood sampling for measurement of NT-proBNP, functional assessment,
      cardiopulmonary exercise testing, echocardiography and radionuclide angiography
      were performed at entry and after 4 months. After 4 months, exercise training
      caused a significant reduction in circulating concentrations of NT-proBNP (2124+/
      397 pg/ml before, 1635+/-304 pg/ml after training, p=0.046, interaction), whereas
      no changes were observed in an untrained heart failure control group. NYHA
      functional class (p=0.02, interaction), maximal (peak VO2: p=0.035, interaction;
      maximal workload: p<0.00001, interaction) and submaximal (workload at anaerobic
      threshold: p=0.001, interaction; rate-pressure product at anaerobic threshold:
      p=0.001, interaction) exercise parameters as well as work efficiency
      (Wattmax/VO2peak: p=0.0001, interaction) were significantly improved. In
      addition, a decrease in left ventricular end-systolic diameter was observed in
      the trained heart failure group (p=0.016). CONCLUSION: Four months of combined
      endurance/resistance training significantly reduced circulating levels of NT
      proBNP in patients with CHF, without evidence of adverse remodelling. Exercise
      training might offer additional non-pharmacological modulation of the activated
      neurohormonal pathways in the setting of CHF.

PMID- 15474695
TI  - Putative contribution of prostaglandin and bradykinin to muscle reflex
      hyperactivity in patients on Ace-inhibitor therapy for chronic heart failure.
AB  - AIMS: In patients with chronic heart failure (CHF), an overactive muscle
      ergoreceptor reflex (chemo-afferents sensitive to the products of muscle work) is
      thought to play an important role in the origin of dyspnoea. We sought to
      investigate whether raised intra-muscular prostaglandins (PG) and bradykinin, as
      estimated by levels within the venous effluent from exercising skeletal muscle
      may be involved in symptom generation through the stimulation of the ergoreflex.
      METHODS AND RESULTS: In 19 stable CHF patients and 12 normal controls,
      cardiopulmonary exercise capacity (peak O2 consumption [peak VO2]) and the
      ergoreflex contribution to ventilation (post-handgrip regional circulatory
      occlusion method) were measured. Venous resting and exercise plasma PGE2,
      PGF1alpha and bradykinin concentrations were assessed. Eleven patients on
      angiotensin converting enzyme inhibitors and 10 controls were challenged with
      ketoprofen infusion (to inhibit PG synthesis and bradykinin activity). Patients
      vs. controls presented lower exercise tolerance (peak VO2 15.9+/-0.7 vs. 33.0+/
      1.3 mL/kg/min), an increased ventilatory response to exercise (VE/VCO2 slope 43+/
      2 vs. 27+/-0.9) (p<0.0001 for all comparisons). The overactive ergoreflex of CHF
      (5.1+/-1.3 vs. 0.1+/-0.3 L/min) was significantly related to the increase in
      PGF1alpha (adjusted R2=0.34, p<0.005) but not PGE2 (adjusted R2=0.16, p>0.05).
      The increased PG and bradykinin productions both at rest and during exercise in
      CHF were attenuated after ketoprofen infusion, associated with ergoreflex
      reduction (-5.1+/-2.2 L/min, p<0.05 vs. saline). CONCLUSION: In CHF, overactive
      muscle ergoreflex is associated with elevated blood concentration of PG and
      bradykinin. Modulation of these metabolite concentrations acutely reduces the
      muscle ergoreflex activity, which suggests a causative role in triggering and/or
      mediating the ergoreflex response.

PMID- 15474696
TI  - Trimetazidine improves left ventricular function and quality of life in elderly
      patients with coronary artery disease.
AB  - AIM: Elderly patients have an increased incidence of ischaemic dilated
      cardiomyopathy often related to diffuse coronary artery disease. Trimetazidine
      protects ischaemic myocardium by improving the myocardial energy utilisation
      during myocardial ischaemia. Aim of the present study was to evaluate the effects
      of trimetazidine on left ventricular (LV) function in elderly patients with
      ischaemic heart disease and reduced LV function. METHODS: Forty seven elderly
      patients (40 males and 7 females, mean age 78+/-3 years) were randomised to
      receive, in addition to standard therapy, either trimetazidine or placebo and
      were evaluated by echocardiography at baseline and after 6 months. RESULTS:
      Trimetazidine and placebo had no effect on either blood pressure or heart rate
      (SBP 2+/-5 vs 4+/-6 mmHg, DBP -1+/-6 vs 3+/-4 mmHg, HR -3+/-7 vs 5+/-9 bpm,
      trimetazidine and placebo compared to baseline, respectively). At the end of the
      study patients randomised to trimetazidine showed a significant greater left
      ventricular function and smaller left ventricular diastolic and systolic
      diameters and volume indices compared to patients receiving placebo (LVEF: 34.4+/
      2.3% vs 27+/-2.8%, p<0.0001; LVEDD: 58.6+/-1.9 mm vs 64+/-1.7 mm, p<0.0001;
      LVESD: 44.5+/-1.1 vs 50+/-0.8 mm, p<0.0001). A significant smaller wall motion
      score index was detected in trimetazidine-treated patients compared to those
      allocated to placebo (1.24+/-0.12 vs 1.45+/-0.19, p<0.01), the percentage change
      in LVEF compared to baseline was also significantly greater in trimetazidine
      treated patients. Diastolic function significantly improved in the trimetazidine
      group while it remained unchanged in the placebo group. At follow-up evaluation,
      patients receiving trimetazidine showed a greater improvement in angina and NYHA
      class than patients allocated to placebo. Quality of life significantly improved
      in all patients treated with trimetazidine while remained unchanged in those
      allocated to placebo. CONCLUSION: In elderly patients with ischaemic
      cardiomyopathy trimetazidine in addition to standard medical therapy has a
      beneficial effect on LV systolic and diastolic function, and improves quality of
      life.

PMID- 15474697
TI  - Statin administration before percutaneous coronary intervention: impact on
      periprocedural myocardial infarction.
AB  - AIMS: Peri-procedural non-Q-wave myocardial infarction is a frequent and
      prognostically important complication of percutaneous coronary intervention
      (PCI). It has been postulated that statins may reduce the rate of myocardial
      injury after PCI. METHODS AND RESULTS: Four hundred and fifty-one patients
      scheduled for elective PCI and not on statins were randomly assigned to either no
      treatment or to statin treatment. Statin administration was started at least 3
      days before the procedure.Incidence of peri-procedural myocardial injury was
      assessed by analysis of creatinine kinase myocardial isoenzyme (CK-MB: upper
      limit of normal [ULN] 3.5 ng/ml) and cardiac troponin I (cTn I, ULN 0.10 ng/ml)
      before, 6 and 12 h after the intervention. A large non-Q-wave myocardial
      infarction was defined as a CK-MB elevation >5 times ULN alone or associated with
      chest pain or ST segment or T wave abnormalities. Median CK-MB peak after PCI was
      1.70 (interquartile ranges 1.10-3.70) ng/ml in the Statin group and 2.20 (1.30
      5.60) ng/ml in the Control group (p=0.015). Median peak of cTnI after PCI was
      0.13 (0.05-0.45) ng/ml in the Statin group and 0.21 (0.06-0.85) ng/ml in the
      Control group (p=0.033). The incidence of a large non-Q-wave myocardial
      infarction was 8.0% in the Statin group and 15.6% in the Control group (p=0.012:
      OR=0.47; 95% CI=0.26-0.86). The incidence of cTnI elevation >5 times ULN was
      23.5% in the Statin group and 32% in the Control group (p=0.043: OR=0.65; 95%
      CI=0.42-0.98). By logistic regression analysis, the independent predictors of CK
      MB elevation >5 times ULN after PCI were intra-procedural angiographic
      complications (OR=9.36; 95% CI=3.06-28.64; p<0.001), statin pre-treatment
      (OR=0.33; 95% CI=0.13-0.86; p=0.023) and age >65 years (OR=2.58; 95% CI=1.09
      6.11; p=0.031). CONCLUSIONS: Pre-procedural statin therapy reduces the incidence
      of large non-Q-wave myocardial infarction after PCI.

PMID- 15474698
TI  - Therapeutic implications of in-stent restenosis located at the stent edge.
      Insights from the restenosis intra-stent balloon angioplasty versus elective
      stenting (RIBS) randomized trial.
AB  - AIMS: In patients with in-stent restenosis (ISR) several anatomic subgroups have
      been identified. ISR affecting the stent edge (EDG) is a poorly characterised
      subgroup with undefined therapeutic implications. We sought to determine the
      implications of ISR affecting the stent EDG. METHODS AND RESULTS: 450 patients
      included in the "Restenosis Intra-stent: Balloon angioplasty vs elective
      Stenting" (RIBS) randomized study, were analysed. EDG ISR was predefined in the
      protocol and the pattern of ISR analysed in a centralized core-lab. Fifty-two
      patients (12%) had EDG ISR (29 stent group, 23 balloon arm). Patients with EDG
      ISR had less severe [minimal lumen diameter (MLD) (0.78+/-0.3 vs 0.66+/-0.3 mm,
      p=0.05)] and shorter lesions (lesion length 10.2+/-6 vs 13.2+/-7 mm, p=0.003).
      Patients with EDG ISR more frequently required crossover (12% vs 3%, p=0.006) but
      eventually the immediate angiographic result and the long-term clinical and
      angiographic outcome was similar to that found in patients without EDG ISR.
      Patients with EDG ISR treated in the balloon and stent arms had similar baseline
      characteristics. However, after intervention, the immediate angiographic result
      was better in the stent arm (MLD 2.79+/-0.4 vs 2.35+/-0.3 mm, p=0.001). This
      difference persisted at late follow-up: MLD (1.93+/-0.7 vs 1.39+/-0.7 mm,
      p=0.01), recurrent restenosis (20% vs 50%, p=0.03). In addition, the 1-year event
      free survival was significantly better (83% vs 52%, log rank p=0.01; Cox HR 0.28,
      95%CI 0.09-0.79) in the stent arm. Moreover, stent implantation was an
      independent predictor of freedom from target vessel revascularization (HR 0.15,
      95%CI 0.03-0.67, p=0.003). CONCLUSIONS: EDG ISR constitutes a specific subgroup
      with relevant therapeutic implications. In patients with EDG ISR, repeat stent
      implantation provides better clinical and angiographic outcome than conventional
      balloon angioplasty.

PMID- 15474699
TI  - Impairment of left atrial function predicts post-operative atrial fibrillation
      after coronary artery bypass graft surgery.
AB  - AIMS: Despite the prevalence of atrial fibrillation (AF) occurring after cardiac
      surgery, its pathophysiology is incompletely understood. Specifically, whether
      left atrial (LA) structural remodelling occurs, contributing to a decrement in
      atrial function and AF has not been previously determined. This study sought to
      determine the relationship between LA function and post-operative AF. METHODS AND
      RESULTS: Three hundred patients undergoing elective coronary artery bypass graft
      surgery were monitored with intraoperative transoesophageal echocardiography to
      determine LA function and dimensions. Post-operative AF was monitored with
      continuous telemetry until hospital discharge. The relationship between clinical
      factors versus LA function and dimension was assessed using multi-variate
      logistic regression. By univariate analysis, patients who subsequently developed
      post-operative AF had a larger LA area and LA appendage area, and lower LA
      ejection fraction measured in the pre-bypass period compared to those without
      subsequent AF. By multivariable analysis, in addition to clinical data including
      age (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.16, P<0.0001),
      body surface area (OR 13.31, 95% CI 1.87-94.5, P=0.0097) and white race, post
      bypass atrial systolic function (atrial filling fraction 0.36, OR 2.51, 95% CI
      1.03-6.13, P=0.04) and abnormal relaxation of the left ventricle (E duration 270
      ms) (OR 2.89, 95% CI 1.34-6.24, P=0.0067) independently increased the risk of
      post-operative AF. CONCLUSION: These results demonstrate that some of the
      structural and functional changes in the atria common to chronic AF in the
      elderly population are also prevalent in surgical patients who develop post
      operative AF, suggesting that post-operative and chronic AF may have similar
      pathophysiology.

PMID- 15474700
TI  - Picotamide, a combined inhibitor of thromboxane A2 synthase and receptor, reduces
      2-year mortality in diabetics with peripheral arterial disease: the DAVID study.
AB  - AIMS: Patients with diabetes are at excessive risk of mortality and
      cardiovascular morbidity. Previous studies suggest that aspirin may be less
      effective in diabetic patients. In this multi-centre, randomized, double blind
      trial picotamide, a dual inhibitor of thromboxane A2 synthase and receptor, was
      compared with aspirin for the prevention of mortality and major cardiovascular
      events in diabetics with peripheral arterial disease (PAD). METHODS AND RESULTS:
      A total of 1209 adults aged 40-75 years with type 2 diabetes and PAD were
      randomized to receive picotamide (600 mg bid) or aspirin (320 mg od) for 24
      months. The cumulative incidence of the 2 years overall mortality was
      significantly lower amongst patients who received picotamide (3.0%) than in those
      who received aspirin (5.5%) with a relative risk ratio for picotamide versus
      aspirin of 0.55 (95% CI: 0.31-0.98%). Events were reported in 43 patients (7.1%)
      on picotamide and 53 (8.7%) on aspirin. The combined endpoint of mortality and
      morbidity had a slightly lower incidence in the picotamide group but this
      difference did not reach statistical significance. CONCLUSION: Picotamide is
      significantly more effective than aspirin in reducing overall mortality in type 2
      diabetic patients with associated PAD.

PMID- 15474701
TI  - Late systemic hypertension and aortic arch geometry after successful repair of
      coarctation of the aorta.
AB  - AIMS: To investigate the role of the geometry of the aortic arch in resting
      hypertension after successful repair of coarctation (CoA). METHODS AND RESULTS:
      105 patients (15.3+/-6 years) with successful repair of aortic CoA underwent
      blood pressure (BP) measurements at rest and magnetic resonance imaging (MRI) of
      the aortic arch and left ventricle. Three categories of aortic arch shape were
      defined based on the global geometry of the aortic arch: gothic, crenel and
      normal. The ratio of the maximum height/transverse diameter of the aortic arch
      (A/T), the percentage of residual stenosis (RS), the growth index of the aortic
      arch segments (GIA), and the left ventricular mass index (LVMI) were calculated.
      Twenty-seven (25.7%) patients had hypertension (HT). HT was more frequent in
      patients with gothic arch geometry (20/44, 45.5%) than in crenel geometry (5/18,
      27.8%) and in normal geometry (2/43, 4.6%) (P<0.001). Resting systolic BP and
      LVMI were significantly higher with gothic arch geometry. In multivariate
      analysis, the only correlates to HT, to level of systolic BP or to LVMI were A/T
      and gothic arch geometry. CONCLUSION: Gothic geometry of the aortic arch is
      associated with resting hypertension in patients having undergone successful
      repair of CoA. This raises concern about methods to harmoniously repair CoA in
      order to prevent or delay rest hypertension in adulthood.

PMID- 15474702
TI  - Pharmacovigilance on MMR vaccine containing L-Zagreb mumps strain.

PMID- 15474703
TI  - Vaccination for avian influenza in Asia.

PMID- 15474704
TI  - Oral priming of mice by recombinant spores of Bacillus subtilis.
AB  - Recombinant Bacillus subtilis spores were employed as a vaccine delivery system
      in a heterologous mucosal priming-parenteral boosting vaccination strategy in the
      mouse model. BALB/c and C57BL/6 mice were orally immunised with recombinant
      spores expressing tetanus toxin fragment C (TTFC) fused to the spore outer coat
      protein CotB, and then subcutaneously boosted with soluble TTFC (without
      adjuvant). Two weeks after boosting, a significantly higher serum TTFC-specific
      IgG response was stimulated in mice primed with recombinant spores (antibody
      concentration of 2600 +/- 915 in C57BL/6 and 1200 +/- 370 ng/ml in BALB/c)
      compared to mice inoculated with wild type spores (650 +/- 250 and 250 +/- 130
      ng/ml, respectively). IgG subclass analysis showed a prevalence of IgG1 and
      IgG2b, indicative of a Th2 type of immune response. Oral administration of
      recombinant spores stimulated also a significant local TTFC-specific IgA
      response. These data show that recombinant spores of B. subtilis are able to
      prime the immune system by the oral route, and that a combined mucosal/parenteral
      strategy can stimulate both local and systemic antigen-specific immune responses.

PMID- 15474705
TI  - Reintroduction of foot-and-mouth disease in Argentina: characterisation of the
      isolates and development of tools for the control and eradication of the disease.
AB  - This paper describes the antigenic and molecular characterisation of foot-and
      mouth disease virus (FMDV) strains isolated during the 2000-2002 epidemic in
      Argentina, and the strategy implemented for disease control. Two different FMDV
      serotypes, O and A, were involved. Of the various field isolates studied, two
      distinct O1 lineages (strains Corrientes/00 and Misiones/00) and two serotype A
      lineages (A/Argentina/00 and A/Argentina/01 prototypes) were identified. The
      genome sequences of these strains were compared with sequences of previous
      regional isolates and sequences of vaccine strains. O1 strains were found to be
      related to regional strains while serotype A strains were found to be more
      distanced from them. The updating of the antigenic composition of the vaccines
      used in the emergency was a key issue, since the outbreaks stopped shortly after
      the implementation of the vaccination programs. The O1 strains quickly
      disappeared from the field following strict control measures and the use of
      vaccines containing O1/Campos strain. However, in the case of the A serotype
      strains, the situation was different, since the use of a vaccine containing
      strain A24/Cruzeiro yielded acceptable levels of protection only after re
      vaccination. Therefore, the new field strains A/Argentina/00 and A/Argentina/01
      were incorporated into the vaccine, leading to an effective control of the
      disease. Viral circulation greatly diminished, as indicated by the significant
      reduction in the number of outbreaks and in the number of animals with antibodies
      against non-structural proteins. Satisfactory levels of protective antibodies
      were subsequently detected in the cattle population (above 75% protection). The
      absence of outbreaks after January 2002 indicated that the epidemic was
      controlled.

PMID- 15474706
TI  - Immunological tools for the assessment of both humoral and cellular immune
      responses in Foxes (Vulpes vulpes) using ovalbumin and cholera toxin B as an
      antigenic model.
AB  - The immune response in the fox (Vulpes vulpes), despite the success of the oral
      rabies vaccine is not well characterized, and specific immunological tools are
      needed. To investigate both the humoral and cellular immune response, we used
      ovalbumin (OVA) and cholera toxin B (CTB) as an antigenic model to set-up ELISA
      and ELISPOT antibodies secreting cells (ASC) assays in the fox model.
      Identification of antibodies that cross-react with fox immunoglobulin was
      performed by Western blot, and their use was adapted for both the ELISA and
      ELISPOT ASC assay. The humoral and cellular specific immune responses were
      assessed after intra-muscular or intra-nasal immunization. Intra-muscular
      immunization resulted in the development of both cellular and humoral anti-OVA
      and anti-CTB responses in peripheral blood mononuclear cells (PBMCs).
      Immunization via the intra-nasal route resulted in the development of a cellular
      and humoral response against CTB in PBMCs. This immune response was confirmed
      using splenocytes from immunized animals by ELISPOT assay at euthanasia. Females
      immunized via the intra-nasal route developed specific anti-CTB IgM, IgA and IgG
      in vaginal fluids after the initial boost (day 26) showing that mucosal
      immunization produces a vaginal immune response in foxes. These immunological
      tools developed here are now available to be adapted to other antigenic models to
      facilitate further immune studies in foxes.

PMID- 15474707
TI  - Humoral immune responses to a protective peptide-conjugate against measles after
      different prime-boost regimens.
AB  - The current live-attenuated measles vaccine leaves many children unprotected
      until they reach the recommended age of vaccination. We have previously shown
      that the short peptide corresponding to the hemagglutinin noose epitope (HNE) of
      the measles virus (MV) hemagglutinin protein induced virus-neutralizing
      antibodies even in the presence of protective levels of anti-whole virus-specific
      antibodies. Here we investigate the immunogenicity of HNE peptide-conjugates of
      diphtheria or tetanus toxoid in mice after active and passive priming with
      antibodies against the peptide, toxoids and conjugates. Both conjugates induced
      high titers of peptide antibodies which crossreacted with the virus and protected
      against a lethal intracranial challenge with a rodent-adapted measles virus, even
      after active priming with homologous or heterologous toxoid or conjugate. Peptide
      specific epitopic suppression was stronger after passive priming with carrier or
      conjugate antibodies, but diphtheria toxoid as a carrier was less susceptible to
      suppression than tetanus toxoid and suppression was overcome by an additional
      boost. Furthermore, prior immunization with peptide-conjugate did not interfere
      with the development of a complete response to a subsequent injection of MV,
      suggesting that the benefits of a follow-up vaccination with the current live
      attenuated vaccine would not be lost. These results underline the potential of
      these peptide-based conjugates as vaccine candidates for use in early infancy to
      close the window of susceptibility before the live-attenuated vaccine can be
      administered.

PMID- 15474708
TI  - Impact of genetic diversity of European-type porcine reproductive and respiratory
      syndrome virus strains on vaccine efficacy.
AB  - The aim of this study was to find out how efficiently pigs that are vaccinated
      with an attenuated porcine reproductive and respiratory syndrome virus (PRRSV)
      vaccine based on a virus from the Lelystad cluster are protected against a
      European wild-type strain from the same or another genetic cluster. Two
      experiments were performed. In each experiment, 5-week-old PRRSV-seronegative
      pigs were vaccinated intramuscularly with 10(4.5) TCID50 of a commercial vaccine
      based on a European virus strain from the Lelystad cluster. Non-vaccinated pigs
      were included as controls. At 5, 9, 15, 20, 28, 35 and 42 days post vaccination
      (PV), broncho-alveolar lavage (BAL) fluids and blood were collected to determine
      vaccine virus quantities. Forty-nine days PV, pigs were challenged intranasally
      with 10(6.0) TCID50 of a European wild-type strain, belonging either to the
      Lelystad cluster (98% nucleotide identity in ORF5 with vaccine strain)
      (experiment A) or to an Italian cluster (84% nucleotide identity in ORF5 with
      vaccine strain) (experiment B). At 5, 9, 15, 20 and 27 days post challenge (PC),
      BAL fluids and blood were collected to determine virus quantities. Vaccine virus
      was first detected in BAL fluids and blood at 5 days PV and reached highest
      quantities between 9 and 15 days PV. One pig was positive in its BAL fluid until
      42 days PV. After challenge, virus was isolated from BAL fluids and blood of all
      non-vaccinated control pigs. All vaccinated pigs challenged with the Lelystad
      strain remained negative for virus, while virus was present in BAL fluids and
      blood of all vaccinated pigs after challenge with the Italian strain. Mean virus
      titres of the vaccinated pigs challenged with the Italian strain were
      significantly lower than those of the non-vaccinated control pigs (P <0.05) at 9,
      15 and 20 days PC. Thus, the genetic diversity within European-type PRRSV may
      affect the efficacy of the current European-type vaccines.

PMID- 15474709
TI  - Suitability of a recombinant Staphylococcus aureus enterotoxin C bovine variant
      for immunodiagnostics and therapeutic vaccine development.
AB  - Recombinant bovine variant of staphylococcal enterotoxin C (SECbovine), produced
      as a NH2-terminal histidine hexamer fusion protein (His6-tagged SECbovine),
      expressed at high levels (25%) in Escherichia coli and affinity purified to
      homogeneity (99.9%), was tested for its diagnostic and therapeutic potentials.
      His6-tagged SECbovine is antigenically authentic to native SECbovine across host
      species, as confirmed by antibody-based capture detection assays using human,
      mouse, rabbit and chicken hyperimmune sera. His6-tagged SECbovine showed
      significant T-cell stimulation activity in vitro. His6-tagged SECbovine was
      immunogenic for IgG in mice (intragastric and intravenous routes) and rabbits
      (intramuscular and subcutaneous routes), dispensing immunoadjuvant
      coadministration. The formation of neutralizing antibodies reduced the severity
      of intoxication symptoms in immunized rabbits. Purified anti-recombinant
      SECbovine rabbit polyclonal IgG neutralized the pyrexic and diarrhoeagenic
      effects of native SEC/SED and recombinant SEC, tested by the kitten and rabbit
      bioassays, respectively.

PMID- 15474710
TI  - Cost-effectiveness analysis of pneumococcal conjugate vaccination in England and
      Wales.
AB  - AIM: To establish whether universal vaccination of infants with the pneumococcal
      conjugate vaccine is likely to be cost-effective from the perspective of the
      health care provider (NHS). METHOD: Two hypothetical cohorts--one vaccinated and
      one unvaccinated--were followed over their lifetime, and the expected net costs
      and benefits (measured in terms of life-years and quality adjusted life years
      (QALY) gained) were compared in the two cohorts. The impact of indirect effects
      of the vaccine, such as herd immunity and serotype replacement, were investigated
      and their relative importance was assessed by performing univariate sensitivity
      analysis and multivariate Monte Carlo simulations. RESULTS: Under base-case
      assumptions (no herd immunity and no serotype replacement) the programme is not
      expected to be cost-effective from the NHS perspective at the current price of
      the vaccine (assumed 30 pounds per dose, three-dose programme). A reduction of
      the cost of the vaccine to half of its current level could bring the cost per
      QALY gained within normally acceptable ranges. If the burden of disease is
      significantly underestimated by current surveillance systems, then the cost per
      QALY gained approaches acceptable levels at the current vaccine price. Herd
      immunity may substantially reduce the burden of pneumococcal disease,
      particularly of pneumonia among the elderly, leading to a significant improvement
      in the cost per life year and QALY gained. Serotype replacement would partly
      offset these benefits, although only with a complete substitution of vaccine
      types with non-vaccine types and a low level of herd immunity, would pneumococcal
      vaccination programme would not be cost-effective. CONCLUSIONS: Conclusions on
      the cost-effectiveness of pneumococcal conjugate vaccine are sensitive to
      assumptions regarding the current burden of pneumococcal disease and the future
      impact that vaccination will have in the unvaccinated and on the future serotype
      distribution. This study quantifies, for the first time, how these indirect
      effects may change the cost-effectiveness of pneumococcal vaccination.

PMID- 15474711
TI  - Economic evaluation of an extended acellular pertussis vaccine programme for
      adolescents in Ontario, Canada.
AB  - PURPOSE: Pertussis is a frequent cause of cough illness in adolescents. In
      Canada, until recently immunization against pertussis in public programmes has
      been restricted to children under the age of 7. The purpose of this analysis was
      to estimate the health and economic impact of an additional booster dose of the
      acellular vaccine in adolescents in Ontario. METHODS: We performed a cost
      effectiveness analysis, based on a predictive spreadsheet dynamic model following
      a cohort of 144,000 adolescents in Ontario from the age of 12 years over a 10
      year-period from the Ontario Ministry of Health (MoH) and societal perspectives.
      The model was used to compare costs and benefits of a combined vaccination
      programme (CVP) including tetanus, diphtheria, and acellular pertussis (dTacp)
      administered at age 12, compared to current practice. RESULTS: From the MoH
      perspective, booster vaccination of dacpT at 12 years via the CVP would produce a
      yearly additional expected cost of CAD $0.52 per adolescent in Ontario with an
      incremental cost-effectiveness ratio of CAD $168 per pertussis case avoided based
      on a 10-year-period. If outcomes are discounted at 3%, the incremental cost
      effectiveness ratio rises to $188/discounted pertussis case avoided. From the
      societal perspective, the CVP would be cost saving CAD $858,106 at 10 years for
      the cohort. Over the 10-year-period, more than 4400 cases of pertussis would be
      prevented with approximately 50 hospital admissions averted. CONCLUSIONS: This
      study suggests that administering a booster dose of dTacp at 12 years of age to
      replace diphtheria and tetanus vaccination at 14 years may reduce the economic
      burden of pertussis treatment in the long term at a reasonable cost.

PMID- 15474712
TI  - Timeliness of MMR vaccination--influence on vaccination coverage.
AB  - Over the last seven years, and especially in 2001, a declining coverage for MMR
      vaccination in 2-year-olds has been noted in Sweden. By recording actual date of
      vaccination in a cohort of almost 4,000 children in a county in central Sweden,
      we found that parents' decision to postpone vaccination by up to 1.5 years beyond
      the stipulated age of 18 months accounted for about half the reported drop in
      2001. Even if coverage thus improves with time, postponed vaccination adds to the
      pool of unprotected children in the population. The design of the current
      national surveillance system overestimates coverage at 2 years and fails to
      record delayed vaccination. To avoid future outbreaks that can appear around
      imported cases of measles it is crucial to attain high coverage levels by timely
      vaccination.

PMID- 15474713
TI  - Comparison of varicella history with presence of varicella antibody in refugees.
AB  - OBJECTIVE: To compare history of varicella with presence of varicella antibody in
      refugees and to determine the number of unnecessary doses of varicella vaccine
      administered to refugee children > or =7 years of age. METHODS: Cross-sectional
      study of refugees > or =7 years of age evaluated between July 2000 and October
      2002 by the Refugee Health Assessment Program at Boston Medical Center. We
      recorded age, sex, region of origin, varicella history, and results of serologic
      testing for presence of varicella antibodies. RESULTS: Eighty-eight percent of
      individuals with a positive history of clinical varicella had varicella antibody;
      65% of those with negative history had varicella antibody. The positive
      predictive value of a history of clinical varicella was 88%. The negative
      predictive value of a negative history was 39%. CONCLUSION: History of varicella
      was not a reliable predictor of presence or absence of varicella antibody in
      refugees. Strategies to protect individuals with negative histories of clinical
      varicella include immediate immunization or serotesting followed by immunization
      of susceptible individuals. Relying on positive histories of clinical varicella
      may leave some individuals susceptible to varicella and impede efforts to
      eliminate varicella in the US.

PMID- 15474714
TI  - Ethical analyses of vaccines grown in human cell strains derived from abortion:
      arguments and Internet search.
AB  - The fact that certain vaccines are grown in cell strains derived decades ago from
      an aborted fetus is a concern for some. To understand such concerns, a
      standardized search identified internet sites discussing vaccines and abortion.
      Ethical concerns raised include autonomy, conscience, coherence, and immoral
      material complicity. Two strategies to analyse moral complicity show that
      vaccination is ethical: the abortions were past events separated in time, agency,
      and purpose from vaccine production. Rubella disease during pregnancy results in
      many miscarriages and malformations. Altruism, the burden of rubella disease, and
      protection by herd immunity argue for widespread vaccination although autonomous
      decisions and personal conscience should be respected.

PMID- 15474715
TI  - Characterisation of adsorbed anthrax vaccine by two-dimensional gel
      electrophoresis.
AB  - The current UK anthrax vaccine is an alum precipitate prepared from static
      culture filtrate of the avirulent, unencapsulated Sterne strain of Bacillus
      anthracis. Protective antigen (PA) is regarded as the major immunogen in the
      vaccine and production conditions are intended to maximize the PA content.
      However, the precise composition of the vaccine is unknown and there are concerns
      that the observed side effects of vaccination may be caused by residual
      enzymatically active toxin components. Two-dimensional gel electrophoresis (2DGE)
      was used to define the protein components of the current UK anthrax vaccine.
      Consistency of composition was assessed by examining batches spanning 14 years of
      vaccine production. The reproducibility of the 2DGE technique was assessed by
      repeated analysis of selected vaccine batches. For two recently produced batches,
      between 86.7 and 88.8% of the spots could be matched. However, for one older
      batch, reproducibility of the spot pattern was considerably less, with a mean
      similarity of 53.4%. This difference may be explained by a change in production
      or because of decay during storage. Variation between the recently produced
      batches ranged from 72.9 to 84.3%, whereas the similarity between these and old
      batches was comparatively low at between 30 and 59%. Our results demonstrate
      that, as expected, the major antigen present in the vaccine is PA. The 83 and 63
      kDa species are dominant but there are numerous lower molecular weight fragments
      resulting from proteolytic cleavage. In addition, we have established the
      presence of the toxin components, oedema factor and lethal factor, and S-layer
      proteins, EA1 and SAP. Mass spectrometry has also enabled us to identify several
      bacterial cell-derived proteins present in the vaccine, including PA, enolase,
      fructose-bisphosphate aldolase, nucleoside diphosphate kinase and a 60 kDa heat
      shock protein. The use of proteomics can provide useful information on the
      antigenic make up of this vaccine and the consistency of vaccine production.

PMID- 15474716
TI  - Protection studies in sheep using affinity-purified and recombinant cysteine
      proteinases of adult Haemonchus contortus.
AB  - Vaccination with a membrane-bound thiol Sepharose-binding fraction (TSBP) of
      adult Haemonchus contortus has been shown to confer significant levels of
      protection against homologous challenge in sheep. This fraction is greatly
      enriched for cysteine proteinase activity. Following fractionation of TSBP by
      anion-exchange chromatography on MonoQ, protection was found to partition with
      those fractions further enriched for cysteine proteinase activity. In this study,
      the cysteine proteinases of adult H. contortus TSBP were specifically purified by
      affinity chromatography using recombinant H. contortus cystatin, a potent
      cysteine proteinase inhibitor. Although only 1-1.5% of total TSBP bound to
      cystatin-Sepharose, this fraction contained 100% of the cysteine proteinase
      activity, as determined by gelatin substrate gel analysis. When used to immunise
      sheep, less than 3microg per dose of this cysteine proteinase fraction was found
      to confer a substantial and repeatable level of protection against homologous
      challenge infection, reducing faecal egg counts by 48 and 28% and worm burdens by
      44 and 46% over two trials. Host serum immunoglobulin levels and abomasal mast
      cell and eosinophil numbers were evaluated, although no correlation with
      protection was observed. Three cathepsin B-like cysteine proteinases present in
      TSBP (hmcp1, 4 and 6) have been identified previously by cDNA library
      immunoscreening. The predicted mature forms of these three cysteine proteinases
      were expressed in bacteria as insoluble, GST-fusion proteins. Following
      solubilisation in urea/DTT, the protective capacity of a cocktail of recombinant
      proteins was evaluated in sheep. Although no reduction in faecal egg counts was
      observed, sheep vaccinated with recombinant cysteine proteinases showed a highly
      significant 38% reduction (P <0.01) in worm burdens.

PMID- 15474717
TI  - Immunogenicity and safety of a low-dose diphtheria, tetanus and acellular
      pertussis combination vaccine with either inactivated or oral polio vaccine as a
      pre-school booster in UK children.
AB  - This open, randomised controlled trial studied the immunogenicity and
      reactogenicity of two combined low-dose diphtheria, tetanus and acellular
      pertussis vaccines (Td5aP-IPV, REPEVAX, Aventis Pasteur MSD; and Td5aP, COVAXIS,
      Aventis Pasteur MSD + OPV, GlaxoSmithKline) in comparison with a standard dose
      diphtheria pre-school booster vaccine (DT2aP-IPV, TETRAVAC, Aventis Pasteur MSD)
      in a population of 3.5-5-year-old children administered concomitantly with
      measles, mumps and rubella vaccine (M-M-R II, Aventis Pasteur MSD). A linked sub
      study aimed to evaluate the immunogenicity and reactogenicity of Td5aP-IPV in a
      population of younger children, aged 3-3.5 years. This study demonstrated non
      inferiority of seroprotection rates for diphtheria and tetanus for the study
      vaccines and comparable immunogenicity for pertussis and polio components of the
      vaccines. Reactogenicity was similar for all three vaccines. The study vaccines
      containing low-dose diphtheria antigen (Td5aP-IPV and Td5aP + OPV) are
      immunogenic and have acceptable reactogenicity for use as a pre-school booster
      vaccine administered concomitantly with MMR.

PMID- 15474718
TI  - Adjuvanticity of native and detoxified adenylate cyclase toxin of Bordetella
      pertussis towards co-administered antigens.
AB  - The cell-invasive adenylate cyclase toxin (CyaA) of Bordetella pertussis was
      shown to be highly antigenic in mice, stimulating serum anti-CyaA IgG antibody
      responses which were able to neutralise the cytotoxic effect of CyaA on J774.2
      macrophage-like cells. The effect of co-administration to mice of the fully
      functional CyaA toxin or a toxin lacking adenylate cyclase enzymic activity
      (CyaA*) with other antigens from B. pertussis, namely pertussis toxin (PT) or
      pertussis toxoid (PTd), filamentous haemagglutinin (FHA) and pertactin (PRN), was
      investigated. CyaA* enhanced the serum IgG antibody responses to each of these
      antigens whereas, with CyaA, only anti-PRN antibody titres showed a modest
      increase. Peritoneal macrophages and spleen cells, collected at 2 weeks post
      immunisation, were cultured and tested for nitric oxide (NO) and IFNgamma
      production, respectively, after stimulation in vitro with heat-killed B.
      pertussis cells or CyaA proteins. NO and IFNgamma production were higher in cells
      collected from mice immunised with CyaA or CyaA* in combination with a PT, FHA
      and PRN antigen mixture than from those taken from mice injected with antigen
      mixture alone, again with CyaA* acting as a better adjuvant than CyaA. The
      apparent enhancement of immune responses to the antigen mixture by CyaA* in
      particular was not paralleled by increased protection of mice against aerosol
      challenge with B. pertussis, but a statistically significant increase in
      protection was seen after intranasal challenge with B. parapertussis.

PMID- 15474719
TI  - Immune response to the Chlamydia trachomatis outer membrane protein PorB.
AB  - The antigenicity of the outer membrane protein PorB during exposure to Chlamydia
      trachomatis was evaluated in humans and its immunogenicity was tested in mice.
      Although natural human infection resulted in strong serological responses to the
      major outer membrane protein (OmpA), antibodies to PorB were low or absent.
      Analogous to the responses observed in humans, mice inoculated with EB or
      challenged with EB produced weak anti-PorB antibody responses. PorB immunization
      of mice previously exposed to EB elicited strong PorB antibody responses. These
      findings support the fact that OmpA antibodies dominate the humoral immune
      response during natural infections and demonstrate that immunization with PorB
      overcomes the lack of immune response to PorB elicited during natural infection.

PMID- 15474720
TI  - Role of the virology diagnosis laboratory in the surveillance of rubella virus
      Cuba 1988/2000.
AB  - In Cuba, on the basis of Measles Elimination Program, the incidence of this
      disease decline, and was necessary to test rubella virus as a possible etiology
      agent that produce fever and rash illness. To reach this goal, Cuba developed
      rubella elimination strategies with integrated epidemiologic and laboratory
      surveillance. In the country, the vaccination program against rubella started in
      1982 by vaccinating 12-14 years old females, with a special surveillance program
      with laboratory study of all suspected cases. Through 1988-2000, the Serology
      Diagnosis Laboratory in the Virology Branch of Pedro Kouri Institute had the
      responsibility to do the measles and rubella surveillance and play a key roll in
      the elimination strategies of these diseases. For confirmation of all suspected
      cases, 8566 serum samples with the suspected diagnosis of measles or rubella from
      different provinces in Cuba were studied in the laboratory using different
      techniques as haemagglutination inhibition test (HIA), ultra micro analytic assay
      (UMA); and in 1995 by the newly introduced IgM ELISA, which was used taken only
      one sample in the acute phase of the disease. These techniques allowed knowing
      that the annual number of reported rubella cases in the country decreased
      substantially after the implementation, in 1986, of the second vaccine policy,
      that of vaccinating women of childbearing age. However, in 1989, was detected an
      outbreak of rubella virus infection that had occurred in young adults male 15-19
      age groups in Matanzas' province. The last three indigenous cases of this disease
      were confirmed by our laboratory in 1995, after national vaccine coverage over
      95%.

PMID- 15474721
TI  - Oral immunization of piglets with recombinant F4 fimbrial adhesin FaeG monomers
      induces a mucosal and systemic F4-specific immune response.
AB  - The importance of adhesins in the pathogenicity of several bacteria resulted in
      studies on their usefulness in vaccines. In this study, the gene of the F4(K88)
      fimbrial adhesin FaeG of the pathogenic enterotoxigenic Escherichia coli (ETEC)
      strain GIS26 was cloned in the pET30Ek-LIC vector and expressed with an N
      terminal His- and S-tag in the cytoplasm of BL21(DE3). Recombinant FaeG (rFaeG)
      subunits were isolated from insoluble cytoplasmic aggregates and refolded into a
      native-like F4 receptor (F4R)-binding conformation. Indeed, the presence of
      conformational epitopes was shown by ELISA and the ability to bind the F4R was
      observed by inhibiting the adhesion of F4+ ETEC to F4R+ villi with increasing
      concentrations of native-like refolded rFaeG subunits. The rFaeG subunits appear
      as monomers, whereas the purified F4 fimbriae are multimers. Oral immunization of
      newly weaned piglets with native-like rFaeG induced a mucosal and systemic F4
      specific immune response, significantly reducing F4+ E. coli excretion from 2
      till 5 days following challenge infection. However, improvement of stability and
      immunogenicity of rFaeG is necessary since a higher F4-specific response was
      obtained following immunization with purified F4 fimbriae. Furthermore, the N
      terminal fusion of a His- and S-tag was not detrimental for binding the F4R,
      supporting the use of FaeG as mucosal carrier. In conclusion, oral immunization
      with a recombinant fimbrial adhesin subunit of Escherichia coli induces a mucosal
      and systemic fimbriae-specific immune response.

PMID- 15474722
TI  - Intranasal immunisation against tetanus with an attenuated Bordetella
      bronchiseptica vector expressing FrgC: improved immunogenicity using a Bvg
      regulated promoter to express FrgC.
AB  - Mice were immunised intranasally with live Bordetella bronchiseptica aroA strains
      possessing plasmids encoding fragment C (FrgC) of tetanus toxin. FrgC was
      expressed either from a constitutive tac promoter (strain GVB120) or the Bvg
      dependent fhaB promoter (strain GVB1543). Serum anti-FrgC antibody titres were
      detected in all mice immunised with GVB1543 and GVB120 but the average titres
      were higher and the responses to FrgC were more consistent in GVB1543 immunised
      animals. This was reflected in the protective immunity conferred by the different
      strains: 100% of GVB1543 immunised mice were protected against tetanus toxin
      challenge whereas only 60% of animals immunised with GVB120 survived tetanus
      challenge. Viability of the B. bronchiseptica vector strain was shown to be
      critical to its efficacy as a vector for FrgC.

PMID- 15474723
TI  - Intranasal immunization with C. muridarum major outer membrane protein (MOMP) and
      cholera toxin elicits local production of neutralising IgA in the prostate.
AB  - Successful control of sexually transmitted diseases (STDs) through vaccination
      will require the development of vaccine strategies that target protective
      immunity to both the female and male reproductive tracts (MRT). In the male, the
      immune privileged nature of the male reproductive tract provides a barrier to
      entry of serum immunoglobulins into the male reproductive ducts, thereby
      preventing the induction of protective immunity using conventional injectable
      vaccination techniques. In this study we investigated the potential of intranasal
      (IN) immunization to elicit anti-chlamydial immunity in BALB/c male mice.
      Intranasal immunization with Chlamydia muridarum major outer membrane protein
      (MOMP) admixed with cholera toxin (CT) resulted in high levels of MOMP-specific
      IgA in prostatic fluids (PF) and MOMP-specific IgA-secreting cells in the
      prostate. Prostatic fluid IgA inhibited in vitro infection of McCoy cells with C.
      muridarum. Using RT-PCR we also show that mRNA for the polymeric immunoglobulin
      receptor (PIgR), which transports IgA across mucosal epithelia, is expressed only
      in the prostate but not in other regions of the male reproductive ducts upstream
      of the prostate. These data suggest that using intranasal immunization to target
      IgA to the prostate may protect males against STDs while at the same time
      maintaining the state of immune privilege within the MRT.

PMID- 15474724
TI  - Characterisation of the antigenic and immunogenic properties of bacterially
      expressed, sexual stage antigens of the coccidian parasite, Eimeria maxima.
AB  - Coccidiosis in poultry is caused by the intestinal parasite Eimeria; it causes
      significant financial losses to the commercial poultry industry worldwide.
      CoxAbic is the first commercially available subunit vaccine against coccidiosis.
      The vaccine consists of affinity purified sexual stage (gametocyte) antigens
      (APGA) isolated from Eimeria maxima. Production of this vaccine is time-consuming
      and laborious and, therefore, a recombinant subunit vaccine substitute for
      CoxAbic is desirable. The genes encoding the two immunodominant components of
      CoxAbic, gam56 and gam82, were cloned into the bacterial expression vector,
      pTRCHisB, and the proteins expressed and purified. Both recombinant proteins were
      recognised by protective chicken antibodies that were raised to APGA, by
      immunoblotting. In a competitive ELISA, a combination of the recombinant proteins
      inhibited the binding of anti-APGA antibodies to APGA by 76%, which was
      comparable to the inhibition of 98% observed when APGA was used as the competing
      protein in the assay. In two breeds of chicken (Australorp and Cobb500), the
      recombinant proteins alone, or in combination, elicited a dose-dependent,
      antibody response that recognised APGA by ELISA, and gametocytes by
      immunoblotting. Together, the results suggested that the development of a
      recombinant subunit vaccine that maintains the antigenic and immunogenic
      properties of the native protein vaccine, CoxAbic, is feasible.

PMID- 15474725
TI  - Dendritic cells infected by recombinant modified vaccinia virus Ankara retain
      immunogenicity in vivo despite in vitro dysfunction.
AB  - The administration of recombinant vaccinia virus Ankara (MVA) encoding a CTL
      epitope (pb9) from a malaria antigen induced activation and maturation of splenic
      dendritic cells (DCs) in vivo. In contrast, incubation of immature dendritic
      cells (iDCs) with the MVA, in vitro, resulted in down-regulation of MHC class I
      molecules and reduced their T-cell stimulatory ability. However, the ability of
      the infected DC to induce an antigen-specific CTL response, in vivo, remained
      intact. Furthermore, the administration of recombinant MVA-infected DC, but not
      pb9 peptide-pulsed DC, boosted and expanded the anti-pb9 CTL response that was
      primed by pb9 peptide-pulsed DC. These data indicate that despite the ability of
      poxviruses to impair DC maturation in vivo, the important ability of MVA to boost
      CD8 T-cell response in vivo is mediated at the level of the infected dendritic
      cells.

PMID- 15474726
TI  - Immunization with C5a peptidase from either group A or B streptococci enhances
      clearance of group A streptococci from intranasally infected mice.
AB  - Group A streptococci (S. pyogenes) are responsible for pharyngitis, impetigo and
      several more serious diseases. Emergence of toxic shock, and necrotizing
      fasciitis, associated with this pathogen over the past 10 years, has generated
      interest in development of a vaccine, which would prevent infections and
      potential serious complications. The highly conserved C5a peptidase that is
      expressed on the surface of group A streptococcus and other streptococcal
      species, associated with human infections, is a prime vaccine candidate. Here, we
      report construction of an inactive form of the peptidase and test its potential
      to induce protection in mice from intranasal challenge with either serotype M1
      and M49 strains of streptococci. Mice were immunized by subcutaneous
      administration of recombinant proteins, mixed with Alum and monophosphoryl lipid
      A (MPL) adjuvants. Control mice were vaccinated with tetanus toxoid in the same
      adjuvants. Preparations of SCPA protein were highly immunogenic in mice. Antibody
      directed against protein from either group A (SCPAw) or group B (SCPBw)
      streptococci neutralized activity associated with both enzymes. Streptococci were
      cleared from the oral-nasal mucosa of mice immunized with vaccine protein more
      rapidly than those immunized with tetanus toxoid. Moreover, immunization with
      either protein enhanced clearance of group A streptococci from the lung. These
      results suggest that parenteral vaccination with SCPBw protein will provide
      protection against infection by either group A or B streptococci.

PMID- 15474727
TI  - Quantifying the impact of hepatitis A immunization in the United States, 1995
      2001.
AB  - Hepatitis A rates have declined to historically low rates in the United States.
      To assess the degree to which this decline was attributable to immunization, we
      correlated changes in the incidence of hepatitis A with increases in immunization
      coverage in a Poisson regression model. In a model allowing for herd immunity, an
      estimated 97,800 hepatitis A cases were averted due to immunization between 1995
      2001, including 39% of potential cases in 2001. Assuming no herd immunity; 32,300
      cases of hepatitis A would have been prevented. Sensitivity analysis showed that
      the number of averted cases in this period could range from 45,500 to 172,900.
      Among children 2-18 years old, vaccination coverage averaged 10% in 2001 and is
      estimated to have prevented 51% of cases in this age group. These results suggest
      that much of the recent reduction of hepatitis A rates is attributable to
      immunization and that immunization has been associated with a strong herd
      immunity effect.

PMID- 15474728
TI  - Do changes in policy affect vaccine coverage levels? Results of a national study
      to evaluate childhood vaccination coverage and reasons for missed vaccination in
      Italy.
AB  - To evaluate the impact of actions taken in Italy since 1998 to improve
      vaccination coverage, a national EPI-survey was performed in 2003. Overall, 4602
      children aged 12-24 months participated in the study; coverage was calculated for
      three doses of DT, polio, HBV, pertussis, and Hib, and for one dose of
      MMR/measles vaccine for children > or =16 months of age. Since 1998, when the
      last national survey was conducted, DT, polio, and HBV coverage have remained
      consistently high (95%), while pertussis, Hib, and MMR/measles significantly
      increased. Pertussis coverage reached the 95% target, and Hib is close to target
      (87%). Improving MMR coverage (77%), however, remains a national priority.

PMID- 15474729
TI  - Improved formulations for existing CBPP vaccines--recommendations for change.
AB  - Contagious bovine pleuropneumonia (CBPP) is an economically important
      transboundary disease, widely present in sub-saharan Africa. Social, cultural and
      economic factors mean that effective vaccination is the only viable control
      policy at present. Unfortunately, contemporary live attenuated vaccines are
      reportedly of limited efficacy and have been unable to control recent outbreaks.
      Efforts to develop newer vaccine technologies are currently underway, although
      with little success to date. This review examines the prospects of success for
      such approaches, and argues that alternative strategies, based upon simple and
      inexpensive changes to current vaccines and protocols are likely to prove far
      more effective in the foreseeable future. Such changes include the use of HEPES
      buffer systems and the inclusion of pH indicators in vaccine media, together with
      restrictions in the use of 1M MgSO4 as a vaccine diluent. These changes can
      increase vaccine yields 10-fold and stability several 100-fold, increase the ease
      of production, provide a significant level of end user-enforceable quality
      control, and ultimately produce a vaccine which should prove effective in the
      field immediately.

PMID- 15474730
TI  - Immunisation against plague by transcutaneous and intradermal application of
      subunit antigens.
AB  - We have investigated immunological responses in BALB/c mice following
      transcutaneous (TC) delivery of fraction 1 (F1) and V subunits from Yersinia
      pestis in conjunction with an enterotoxin-derived adjuvant (cholera toxin, CT).
      It was found that two or more TC applications of F1 and V subunits (admixed with
      cholera toxin) served to elicit significant levels of anti-F1 and V antibodies in
      the serum of immunised mice. IL-6 secretion from cultured splenocytes derived
      from immunised mice indicated that a single TC application of F1 and V subunits
      (admixed with cholera toxin) conferred a cell-mediated response. As compared with
      intranasal or direct intradermal injection of F1 and V, the numbers of F1/V
      specific antibody-forming cells in the spleens of animals immunised by TC
      application of F1 and V (admixed with CT) was relatively low. It was noted that
      TC application of F1 and V admixed with CT was very effective for priming
      responses that were boosted by intranasal or intradermal routes. Similarly, it
      was found that TC application of F1 and V admixed with CT could be used to
      efficiently boost pre-existing responses engendered by intradermal injection or
      intranasal instillation of F1 and V. In order to assess if TC application of F1
      and V admixed with CT could protect experimental animals from plague, immunised
      mice were injected with a virulent strain of Y. pestis. It was found that two TC
      applications of F1 and V admixed with CT conferred only limited protection
      against 10(2) MLDs. However, three TC applications of F1 and V admixed with CT
      conferred solid protection against 10(2) MLDs. Hence we have shown, for the first
      time, that TC application of F1 and V admixed with CT can protect animals against
      challenge with a virulent strain of plague causing bacteria. These data suggest
      that transcutaneous immunisation may be a simple and non-invasive method for
      immunising individuals against plague.

PMID- 15474731
TI  - Expression of Bacillus anthracis protective antigen in transgenic chloroplasts of
      tobacco, a non-food/feed crop.
AB  - The Centers for Disease Control (CDC) lists Bacillus anthracis as a category A
      agent and estimates the cost of an anthrax attack to exceed US$ 26 billion per
      100,000 exposed individuals. Concerns regarding anthrax vaccine purity, a
      requirement for multiple injections, and a limited supply of the protective
      antigen (PA), underscore the urgent need for an improved vaccine. Therefore, the
      83 kDa immunogenic Bacillus anthracis protective antigen was expressed in
      transgenic tobacco chloroplasts. The PA gene (pag) was cloned into a chloroplast
      vector along with the psbA regulatory signals to enhance translation. Chloroplast
      integration of the transgenes was confirmed by PCR and Southern blot analyses.
      Crude plant extracts contained up to 2.5 mg full length PA/g of fresh leaf tissue
      and this showed exceptional stability for several months in stored leaves or
      crude extracts. Maximum levels of expression were observed in mature leaves under
      continuous illumination. Co-expression of the ORF2 chaperonin from Bacillus
      thuringiensis did not increase PA accumulation or induce folding into cuboidal
      crystals in transgenic chloroplasts. Trypsin, chymotrypsin and furin proteolytic
      cleavage sites present in PA were protected in transgenic chloroplasts because
      only full length PA 83 was observed without any degradation products. Both CHAPS
      and SDS detergents extracted PA with equal efficiency and PA was observed in the
      soluble fraction. Chloroplast-derived PA was functionally active in lysing mouse
      macrophages when combined with lethal factor (LF). Crude leaf extracts contained
      up to 25 microg functional PA/ml. With an average yield of 172 mg of PA per plant
      using an experimental transgenic cultivar grown in a greenhouse, 400 million
      doses of vaccine (free of contaminants) could be produced per acre, a yield that
      could be further enhanced 18-fold using a commercial cultivar in the field.

PMID- 15474732
TI  - Immunogenicity of recombinant LT-B delivered orally to humans in transgenic corn.
AB  - Previous clinical studies have demonstrated the feasibility of using edible
      transgenic plants to deliver protective antigens as new oral vaccines. Transgenic
      corn is particularly attractive for this purpose since the recombinant antigen is
      stable and homogeneous, and corn can be formulated in several edible forms
      without destroying the cloned antigen. Transgenic corn expressing 1 mg of LT-B of
      Escherichia coli without buffer was fed to adult volunteers in three doses, each
      consisting of 2.1 g of plant material. Seven (78%) of nine volunteers developed
      rises in both serum IgG anti-LT and numbers of specific antibody secreting cells
      after vaccination. Four (44%) of nine volunteers also developed stool IgA.
      Transgenic plants represent a new vector for oral vaccine antigens.

PMID- 15474733
TI  - Strong local and systemic protective immunity induced in the ferret model by an
      intranasal virosome-formulated influenza subunit vaccine.
AB  - The proliferation of influenza viruses causes costly, recurrent, annual
      epidemics. Current vaccines, mainly administered parenterally, have been shown to
      be suboptimal in terms of efficacy, particularly where local IgA responses are
      concerned. Recent investigations of virosomes as delivery systems for viral HA
      and NA antigens have demonstrated an improved immune response. This paper
      investigates the efficacy of a novel virosome-based intranasal influenza vaccine
      by its ability to reduce disease symptoms and its effect on viral shedding in
      nasal secretions of immunised ferrets. The use of ferrets in the study of
      influenza vaccines is based on the good comparability between ferret and human
      response to the disease. Intranasal, as opposed to parenteral, administration of
      a trivalent virosome-based subunit vaccine adjuvanted with HLT provides an almost
      total prevention of virus shedding combined with a high level of immunological
      protection against homologous virus challenge. The ease of application of an
      intranasal vaccine may have positive repercussions in the adoption of influenza
      vaccinations, particularly in 'at-risk' groups.

PMID- 15474734
TI  - A review of approaches for classifying benthic habitats and evaluating habitat
      quality.
AB  - We have assessed the current state of knowledge relative to methods used in
      assessing sub-tidal benthic habitat quality and the classification of benthic
      habitats. While our main focus is on marine habitat, we extensively draw on
      knowledge gained in freshwater systems where benthic assessment procedures are at
      an advanced stage of maturity. We found a broad range of
      sophistication/complication in terms of the methods applied in assessing and
      mapping benthic habitats. The simplest index or metric involved some assessment
      of species richness, while the most complicated required utilizing multi-variate
      analysis. The simplest mapping attempts equated physical substrate with benthic
      habitat while the most sophisticated relied on extensive environmental preference
      and groundtruth data for species of concern. The leading edge of methods for
      benthic habitat mapping involves combining the advances in optical and acoustic
      methods that allow for routine classifying and mapping of the seafloor with
      biological and habitat data for species of concern. The objective of this melding
      of dispirit methods is to produce benthic habitat maps with broad system wide
      coverage and sound biological underpinning. It is clear that the disparity in
      information density between the physical and biological sides of the equation
      currently hinder applicability and acceptability of benthic habitat mapping
      efforts. In addition to the lack of basic information on the biological and
      environmental tolerances of targeted species, the proliferation of metrics for
      characterizing and assessing biological conditions further clouds the usefulness
      of any broad scale mapping attempt. The problem of data density mismatch between
      physical and biological methods will likely not be solved until acoustic methods
      can routinely resolve the elusive biological components that make a physical
      substrate a habitat.

PMID- 15474735
TI  - Effect of sequentially combining methanol and acetic acid on the performance of
      biological nitrogen and phosphorus removal.
AB  - A sequentially combined carbon (SCC) source using methanol and acetic acid was
      investigated for biological nitrogen and phosphorus removal in a wastewater
      treatment process consisting of an anoxic zone, an oxic zone and a final settling
      tank. The anoxic zone was divided into two separate anoxic zones to feed methanol
      in the first anoxic zone and acetic acid in the second anoxic zone. Methanol and
      acetic acid, each as the sole carbon source, were also tested for comparison. The
      use of SCC was superior in nitrogen removal with all combined COD ratios of
      methanol/acetic acid tested, yielding 95.8-97% efficiency (less than 1 mg N/l in
      the final effluent). The highest phosphorus removal of above 92% (final effluent
      concentration of 0.12 mg P/l) was achieved when only acetic acid was used at a
      quantity equivalent to 50 mg COD/l. However, when SCC was used, the acetic acid
      dosage of 50 mg COD/l could be reduced down to 20 mg COD/l when 30 mg COD/l was
      replaced by methanol; this resulted in a final effluent phosphorus concentration
      of 0.6 mg P/l. Additional benefits of SCC included the excellent sludge settling
      properties compared to the use of methanol or acetic acid alone.

PMID- 15474736
TI  - A fuzzy knowledge-based decision support system for groundwater pollution risk
      evaluation.
AB  - In this paper we propose a decision support system that can provide information
      on the environmental impact of anthropic activities by examining their effects on
      groundwater quality. We use the combined value of both intrinsic vulnerability of
      a specific local aquifer, obtained by implementing a parametric managerial model
      (SINTACS), and a degree of hazard value, which takes into account specific human
      activities. Incomplete information is notoriously common in environmental
      planning. To overcome this deficiency we apply an algorithmic and a qualitative
      approach, based on expert judgment incorporated into the system's knowledge base.
      The decision support system takes into account the uncertainty of the
      environmental domain by using fuzzy logic and evaluates the reliability of the
      results according to information availability.

PMID- 15474737
TI  - Leaching characteristics of solid wastes from thermal power plants of western
      Turkey and comparison of toxicity methodologies.
AB  - Use of lignite in power generation has led to increasing environmental problems
      associated not only with gaseous emissions, but also with the disposal of ash
      residues. In particular, use of low quality coals with high ash content results
      in huge quantities of both fly and bottom ashes to be disposed of. A main problem
      related to coal ash disposal is the heavy metal content of the residue. In this
      regard, experimental results of numerous studies indicate that toxic trace metals
      may leach when fly and bottom ashes are in contact with water. In this study, fly
      and bottom ash samples obtained from thermal power plants, namely Yenikoy,
      Kemerkoy and Yatagan, located at the southwestern coast of Turkey, were subjected
      to toxicity tests such as the extraction (EP) and toxicity characteristic
      leaching (TCLP) procedures of the US Environmental Protection Agency (USEPA) and
      the so-called 'Method A' extraction procedure of the American Society of Testing
      and Material (ASTM). The geochemical composition of ash samples showed variations
      depending on the coal burned in the plants. Furthermore, the EP, TCLP and ASTM
      toxicity tests showed variations such that the ash samples were classified as
      'toxic waste' based on EP and TCLP results whereas they were classified as 'non
      toxic' based on ASTM results, indicating test results are pH dependent. When the
      extraction results were compared with the chemical composition of water samples
      obtained in the vicinity of the thermal power plants, it was found that the
      results obtained using the ASTM procedure cannot be used to predict subsurface
      contamination whereas the EP and TCLP procedures can be used.

PMID- 15474738
TI  - Regional inventory of soil surface nitrogen balances in Indian agriculture (2000
      2001).
AB  - Nitrogen regulates several ecological and biogeochemical processes and excess
      reactive nitrogen in the environment can lead to pollution problems, including
      the deterioration of air quality, disruption of forest processes, acidification
      of lakes and streams, and degradation of coastal waters. Much of the excess
      nitrogen inputs are related to food and energy production. An important step to
      understanding the sources of nitrogen and ultimately defining solutions to excess
      nitrogen is to describe the geographic distribution of agricultural nitrogen
      contributions from different regions. In this study, soil surface nitrogen loads
      were quantified for different states of India for the period 2000-2001. Nearly
      35.4 Tg of nitrogen has been estimated as inputs from different sources, with
      output nitrogen from harvested crops of about 21.20 Tg. The soil surface nitrogen
      balance, estimated as inputs minus outputs, is found to be about 14.4 Tg surplus
      from the agricultural land of India. Livestock manure constituted a major
      percentage of total inputs (44.06%), followed by inorganic fertilizer (32.48%),
      atmospheric deposition (11.86%) and nitrogen fixation (11.58%). Nitrogen balance
      varied from deficit to surplus for different states. The highest nitrogen surplus
      was found in Uttar Pradesh (2.50 Tg) followed by Madhya Pradesh (1.83 Tg), Andhra
      Pradesh (1.79 Tg), etc. A negative nitrogen balance was found in Orissa (-0.01
      Tg), Andaman Nicobar Islands (-0.32 Tg) and for some of the northeastern states.
      Major fertilizer consumption states were found to be Tamilnadu (204 kg/ha),
      Haryana (132 kg/ha), Punjab (148 kg/ha), followed by others. Similarly, nitrogen
      inputs from total livestock excretions were found to be high for Kerala (616
      kg/ha), Jammu and Kashmir (389 kg/ha), Tamil Nadu (338 kg/ha), etc. The average
      nitrogen surplus of about 54 kg/ha observed for the agricultural land of the
      entire country of India is comparatively higher than the average surplus of about
      31 kg/ha reported for European countries. These results, obtained from nutrient
      mass balance calculations, will be useful to formulate nutrient management plans
      relating to fertilizer usage, livestock management and for adopting some best
      management strategies at a state level in India.

PMID- 15474739
TI  - Erosive separation of organic coatings from fibrous substrates.
AB  - The separation of organic coatings from fibrous substrates is a key problem in
      recycling processes. This problem applies to carpets, technical textiles and
      automotive interior components. This paper reports about results of laboratory
      studies involving the application of high-speed liquid jets to solve this
      problem. Results from high-speed video images are used to qualify the principal
      erosion process. It is shown that the coating material is first ground by the
      jet; the generated erosion debris is then pushed through the permeable fibrous
      fabric of the substrate. It is also found that threshold conditions exist for the
      coating grinding process and for the debris transportation. These threshold
      conditions depend on target composition and process parameters. A
      phenomenological separation model is introduced. The influence of key process
      parameters, namely jet velocity, exposure time, stand-off distance and impact
      angle, is also investigated. It is found that high-speed liquid jets are suitable
      tools for separating organic coatings completely and selectively from fibrous
      substrates. Recommendations on how to optimise the erosion process are derived
      from the results.

PMID- 15474740
TI  - A river water quality management model for optimising regional wastewater
      treatment using a genetic algorithm.
AB  - To achieve water quality goals and wastewater treatment cost optimisation in a
      river basin, a water quality management model has been developed through the
      integration of a genetic algorithm (GA) and a mathematical water quality model.
      The developed model has been applied to the Youngsan River, where water quality
      has decreased due to heavy pollutant loads from Kwangju City and surrounding
      areas. Pollution source, land use, geographic features and measured water quality
      data of the river basin were incorporated into the Arc/View geographic
      information system database. With the database, the management model calculated
      treatment type and treatment cost for each wastewater treatment plant in the
      river basin. Until now, wastewater treatment policy for polluted rivers in Korea
      has been, first of all, to construct secondary treatment plants for untreated
      areas, and secondarily, to construct advanced treatment plants for the river
      sections whose water quality is impaired and for which the water quality goal of
      the Ministry of Environment is not met. Four scenarios that do not use the GA
      were proposed and they were compared with the results of the management model
      using the GA. It became clear that the results based on the GA were much better
      than those for the other four scenarios from the viewpoint of the achievement of
      water quality goals and cost optimisation.

PMID- 15474741
TI  - Development of performance indicators for small Quebec drinking water utilities.
AB  - This study presents a comparative performance analysis of small drinking water
      utilities in Quebec (Canada). The investigation bears on 10 utilities that use
      surface water or groundwater under the direct influence of runoff and apply
      chlorination as the only treatment before distribution. The utilities under study
      were divided into two groups: four utilities that had never or rarely provided
      water violating provincial drinking water microbiological standards (relating to
      fecal and/or total coliform bacteria), called nonproblematic utilities, and six
      utilities that quite often violated the standards, designated as problematic
      utilities. The objective of the study is to develop utility performance
      indicators capable of explaining current and historical distributed water
      quality. Indicators are based on operational, infrastructure, and maintenance
      characteristics of utilities that are integrated using a multivariable weight
      based index. Results show that utility performance indicators are systematically
      better for the nonproblematic group of utilities as compared to the problematic
      group. Disinfection-related, infrastructure, and maintenance variables are those
      that most contributed to indicator values. Sensitivity analyses served to assess
      the impact on indicator results of excluding variables and changing their
      weights.

PMID- 15474742
TI  - Fisheries in Chilika lake: how community access and control impacts their
      management.
AB  - The status of fisheries in Chilika lake on the east coast of India is in a
      critical state. Local fishing communities feel that catches have reduced
      significantly and they face more hardships now to sustain their livelihoods. The
      study presents findings from field research and argues that notions of access are
      linked to community perceptions of the resource, the extent of authority they
      have to make decisions related to access and use rights and the traditional
      management strategies. State interventions through mechanization and new
      regulations have undermined the traditional management strategies leading to
      conflicts between different stakeholders and decline in traditional fisheries.
      There is a growing realization that without traditional fishing community's
      participation it is not possible to ensure sustainable use of the lake resources.
      Legitimizing community access and use rights is one of the key factors for
      successful management of fisheries.

PMID- 15474743
TI  - Process intensification in the textile industry: the role of membrane technology.
AB  - Process intensification is a concept that was recently introduced in the chemical
      industry for the purpose of reducing environmental emissions, energy consumption
      and materials consumption. The principle of process intensification can be used
      in related industries as well; textile finishing is an exemplary activity where
      it may have a significant long-term added value. Membrane technology can be a key
      factor in the recycling and reuse of energy, water and chemicals. In this paper,
      an integral approach for treatment of aqueous process streams in the textile
      finishing industry is proposed. The proposed process includes microfiltration
      pretreatment of used finishing baths, followed by a dual nanofiltration (NF)
      unit. These can be operated at elevated temperatures so that no further energy is
      needed for preheating of recycle streams. In the proposed treatment scheme, the
      first of the NF units uses a loose nanofiltration membrane that retains most of
      the organic fraction but not the dissolved salts. The second unit uses a tight
      nanofiltration membrane, which produces a permeate fraction that can be directly
      reused, and a concentrated brine that is fed to a membrane crystallizer. In this
      unit, salts are recovered and recycled for use in new dye baths. The concentrate
      stream from the first NF unit is fed to a membrane distillation unit, where the
      high temperature is advantageously used for further concentration. The remaining
      fraction is not reusable, given the fact that most dyes are hydrolyzed after
      exhaustion of the bath, but has a significant energetic value, which can be
      utilized for compensation of energy losses and preheating of suppletion water, by
      using an incineration process with energy recovery. The concept was not tested
      experimentally, but a simulation for a 500 m3/d production unit shows that it is
      feasible, although modifications may be necessary depending on the nature of the
      finishing baths. Furthermore, the membrane choice in the first NF unit is a
      critical aspect.

PMID- 15474744
TI  - Muscle ultrasound in children: normal values and application to neuromuscular
      disorders.
AB  - In this study, 105 healthy children (45 to 156 months old, 57 girls) were
      examined using ultrasound (US) imaging to obtain reference values of muscle
      dimensional and aspect parameters. We measured biceps and quadriceps sizes and
      subcutaneous tissue thickness. To quantify muscle aspect, we calculated muscle
      density, inhomogeneity and white-area index by digital image analysis. Age-,
      weight- and gender-dependencies were discussed. We demonstrated earlier that the
      complete set of parameters allows for differentiation between myopathies and
      neuropathies in adults, with high sensitivity. In this study, we investigated if
      these parameters have additional value in the diagnostic evaluation of 36
      children with proven neuromuscular disease (20 Duchenne muscular dystrophy, 16
      neuropathies). We found that density analysis provides a sensitive method for
      distinguishing between healthy children and children with neuromuscular
      disorders. We have also found that more detailed aspect analysis is necessary to
      further distinguish between these types of neuromuscular disorders in children.
      In conclusion, this set of normal muscle parameters can be used to help diagnose
      neuromuscular disorders in children. It will also facilitate follow-up in disease
      progression and therapy.

PMID- 15474745
TI  - The influence of visual contrast on visually evoked cerebral blood flow
      responses.
AB  - Transcranial Doppler (TCD) could be used to evaluate the visually evoked cerebral
      blood flow responses (VEFRs) during graded visual cortex activity. The purpose of
      the study was to evaluate the effects of visual contrasts on VEFR. The records
      were made from 30 healthy volunteers aged 38.0 +/- 9.6 years. The stimulus was a
      black-and-white checkerboard with visual contrasts of 1%, 10% and 100%. The VEFRs
      were measured in the posterior cerebral artery using TCD. We found that the VEFRs
      at 100% visual contrast were 36% higher than those at 10% visual contrast (p <
      0.01). The VEFRs at 10% visual contrast were 81% higher than those at 1% visual
      contrast (p < 0.01). The linear regression showed significant relationships
      between the visual contrast and the VEFR (r = 0.61, p < 0.01). We have concluded
      that TCD monitoring of VEFR detects the changes of the blood flow in the visual
      cortex and that TCD could allow an assessment of neurovascular coupling.

PMID- 15474746
TI  - Different behaviors of microbubbles in the liver: time-related quantitative
      analysis of two ultrasound contrast agents, Levovist and Definity.
AB  - The differences in time-related changes of liver images were compared
      quantitatively between Levovist and Definity. A total of 40 rabbits were assigned
      to eight groups according to the timing of taking enhanced liver images at 1, 3,
      5, 7, 9, 11, 13 and 15 min by intermittent harmonic imaging using Levovist or
      Definity (30 microL/kg) and another 40 rabbits for Definity (50 microL/kg).
      Intensity changes between before and after enhancement in the portal vein (I-PV)
      and liver parenchyma (I-LP) were analyzed. I-PV was greater than I-LP at the 1-
      and 3-min phases of enhancement and I-LP became greater than I-PV with Levovist
      after 5 min. However, I-PV was higher than I-LP in all phases with Definity.
      Different time-intensity curves of these two agents will indicate discrete
      behaviors of microbubble hemodynamics in the liver; Levovist becomes accumulated
      in the liver, whereas Definity acts as a blood pool contrast agent, without
      accumulation.

PMID- 15474748
TI  - Distribution of left ventricular longitudinal peak systolic strain and impact of
      low frame rate.
AB  - The myocardium has complex 3-D motion that is frequently described using
      ultrasound (US) Doppler techniques that are limited to recording velocities in
      one dimension only. Studies using 3-D tagged magnetic resonance show that the
      myocardium has strain components with varying angles throughout the myocardium.
      Despite this, there seems to be a belief that the left ventricular longitudinal
      strain distribution should be homogeneous. When measuring myocardial strain,
      there are several parameters for the clinician to decide on, one of them being
      recording frame rate. The current study aims to further investigate the alleged
      homogeneity of the longitudinal myocardial strain distribution and to discover
      the impact that the frame rate has on these measurements. Myocardial strain was
      measured in 43 healthy individuals at different frame rates. Analysis of variance
      results clearly demonstrate that the strain is not uniformly distributed over the
      wall; there seems to be an increasing strain from apex toward the base. However,
      subjects exist with different distributions; thus, it is not possible to conclude
      that certain strain patterns are normal. Reduced frame rate had a highly
      significant impact on the measured strain results and it is seen that, at low
      frame rates, the strain values were reduced.

PMID- 15474747
TI  - In patients with pseudoxanthoma elasticum a thicker and more elastic carotid
      artery is associated with elastin fragmentation and proteoglycans accumulation.
AB  - Skin biopsies in patients with pseudoxanthoma elasticum (PXE) show elastic fiber
      fragmentation and calcium and proteoglycans accumulation. Assuming such changes
      to be present in the artery wall as well, we studied the influence of such
      alterations on function and structure of the human common carotid artery (CCA).
      Indeed, elastin fragmentation and increased calcium and proteoglycans content
      were present in the arteries of the two PXE patients examined. Internal diameter,
      distension and intima-media thickness (IMT) in the CCA of PXE patients (n = 19)
      and controls (n = 39) were determined by ultrasound (US). Pulse pressure was
      assessed in the brachial artery. The distensibility and compliance coefficients
      as well as the Young's modulus were calculated. Diameter and pulse pressure were
      not significantly different in PXE patients and controls. The distensibility and
      compliance coefficients were significantly greater in older PXE patients than in
      older controls. The distensibility coefficient decreased with age in both PXE
      patients and in controls. Unlike in controls, the compliance coefficient did not
      decrease and the Young's modulus barely increased with age in PXE patients. IMT
      was significantly greater at both younger and older ages and the Young's modulus
      was significantly smaller at older ages in PXE patients than in controls. The
      carotid artery is thicker and more elastic in PXE patients than in control
      subjects; differences are most pronounced at older ages. These alterations might
      be explained by the elastin fragmentation and proteoglycans accumulation as
      observed in these patients.

PMID- 15474749
TI  - Quantitative ultrasound at the calcaneus in corticosteroid-treated male patients
      with bronchial asthma.
AB  - The aim of the study was to assess skeletal status in bronchial asthma male
      patients after long-term corticosteroid (CSt) therapy. A total of 25 men patients
      (mean age 53.8 +/- 11.6 years) were compared with 343 men: 256 control men
      without fractures (mean age 54.4 +/- 13.1 years) and 87 men with previous
      osteoporotic fractures (mean age 54.7 +/- 11.6 years). The mean age and body size
      did not differ among groups studied. The duration of CSt therapy expressed as
      median was 6 years (range 1 to 30 years), and a mean dose equivalent to
      prednisone was 9.3 +/- 4.5 mg. Skeletal status was evaluated by quantitative
      ultrasound (QUS) measurements at the heel using the Achilles system (Lunar),
      which measures speed of sound (SOS) in m/s and broadband ultrasound (US)
      attenuation (BUA) in dB/MHz. The Achilles software calculates also a stiffness
      index (SI) in %. The CV% values were: 2.48% for BUA, 0.33% for SOS and 2.56% for
      SI. Values of BUA, SOS, SI, T-score and Z-score in patients were significantly
      lower than in controls and did not differ between patients and men with
      fractures. The duration of CSt therapy and childhood and current calcium daily
      intake did not influence skeletal variables measured. ROC analysis was performed
      to assess the discriminatory capability of calcaneal QUS for fractured and CSt
      treated patients by calculating the area under the ROC curve (AUC). AUCs were:
      0.74 +/- 0.027 and 0.72 +/- 0.05 for SOS, 0.71 +/- 0.03 and 0.66 +/- 0.05 for BUA
      and 0.74 +/- 0.03 and 0.71 +/- 0.05 for SI, respectively. Concluding, in male
      patients with bronchial asthma on prolonged CSt therapy, skeletal status was
      affected, and calcaneal QUS measurements can be a useful tool in the assessment
      of skeletal side effects after long-term CSt treatment.

PMID- 15474750
TI  - Is pericardium a suitable calibration reference in integrated backscatter
      analysis?
AB  - To evaluate if pericardium is a suitable calibration reference in the integrated
      backscatter (IBS) analysis, the grossly normal pericardial specimens from 23
      patients without a history of pericarditis were mounted on a steel platform and
      immersed in a 0.9% saline bath. The 2-D IBS images acquired at the uniform time
      gain compensation settings of 50 and 70 dB were analyzed. For the pericardial
      IBS, the limits of agreement for intraobserver and interobserver measurements
      were -1.2 to 1.4 dB and -1.6 to 2.2 dB, respectively. However, the calibrated IBS
      intensity of the pericardium presented a rather wide range of variation and was 
      13 +/- 5 (-5 to -29) and -10 +/- 4 (-4 to -22) dB at the overall gain settings of
      50 and 70 dB, respectively. Conclusively, pericardium may not be an ideal IBS
      calibration reference in a population study of cardiac tissue characterization.

PMID- 15474751
TI  - A thin-walled carotid vessel phantom for Doppler ultrasound flow studies.
AB  - A technique is discussed for producing a robust ultrasound (US)-compatible flow
      phantom that consists of a thin-walled silicone-elastomer vessel with a lumen of
      arbitrary geometry, embedded in an agar-based tissue-mimicking material (TMM).
      The TMM has an acoustic attenuation of 0.56 dB cm(-1) MHz(-1) at 5 MHz, with
      nearly linear frequency-dependence and acoustic velocity of 1539 +/- 4 m s(-1).
      The vessel-mimicking material (VMM) has an acoustic attenuation of 3.5 dB cm(-1)
      MHz(-1) with linear frequency-dependence and an acoustic velocity of 1020 +/- 20
      m s(-1). Scattering particles, which are added to the VMM to increase
      echogenicity and add speckle texture, lead to higher attenuation, depending on
      particle concentration and frequency. The VMM is stable over time, with a Young's
      elastic modulus of 1.3 to 1.7 MPa for strains of up to 10%, which mimics human
      arteries under typical physiological conditions. The phantom is sealed to prevent
      TMM exposure to air or water, to avoid changes to the acoustic velocity.

PMID- 15474752
TI  - The effects of low-intensity ultrasound on peripheral nerve regeneration in
      poly(DL-lactic acid-co-glycolic acid) conduits seeded with Schwann cells.
AB  - This study attempted to improve the efficacy of peripheral nerve regeneration,
      using the stimulus of low-intensity ultrasound (US) on poly(DL-lactic acid-co
      glycolic acid) (PLGA) nerve guidance conduits seeded with Schwann cells. The
      possible differences between the ultrasonic effects of biodegradable and
      nonbiodegradable materials used as conduits were also investigated, by comparison
      with a group of silicone conduits. The PLGA conduits were seeded with or without
      Schwann cells (6 x 10(3) cells). All conduits were implanted 10 mm into right
      sciatic nerve defects in rats and underwent 12 ultrasonic treatment sessions over
      2 weeks. Ultrasound was applied at a frequency of 1 MHz and an intensity of 0.2
      W/cm2 spatial average temporal peak (SATP) for 5 min/day. Histologic analysis was
      used to evaluate the recovery of the nerve after 6 weeks. Ultrasonically
      stimulated animals, especially those whose PLGA conduits, seeded with Schwann
      cells, exhibited considerably more myelinated axons with a larger mean area at
      the midconduit of the implanted grafts than those in any other group. Ultrasonic
      stimulation of a silicone conduit induced the generation of mass fibrous tissues
      that covered the nerve conduits and retarded axon regeneration. These results
      showed that ultrasonic stimulation may directly stimulate the seeded Schwann
      cells within the PLGA conduits to regenerate nerves. Nevertheless, the applying
      of US may not allow incorporation with the silicone rubber as a material from
      which to form nerve guidance conduits.

PMID- 15474753
TI  - Time to menopause in relation to PBBs, PCBs, and smoking.
AB  - OBJECTIVES: Because halogenated biphenyl exposure is suspected to disrupt
      endocrine function, we assessed time to menopause in women aged 24 years and
      older who were exposed orally to polybrominated biphenyls (PBBs) and
      polychlorinated biphenyls (PCBs) (n = 874). We also examined smoking in relation
      to menopause. METHODS: To define menopausal status, women were interviewed in
      1997 and asked whether they had had any menstrual periods in the previous year,
      why their menstrual periods had stopped (e.g. surgery), and age at their last
      menstrual period. Serum PBB and PCB taken at enrollment (1976-1978) into the
      Michigan PBB registry was used as the measure of halogenated biphenyl exposure.
      Women whose menopause occurred before their PBB exposure were excluded.
      Proportional hazard modeling was used to analyze the "risk" for menopause in
      relation to exposure. Premenopausal women contributed person-time until their
      interview date, at which time they were censored. RESULTS: We did not find an
      association between either PBB or PCB exposure and time to menopause. Women who
      were current smokers had a shorter time to menopause than never smokers
      (menopause ratio 2.02, 95% C.I. 1.21-3.37). Time to menopause was shortest among
      women who reported started smoking when they were <18 years of age, smoked at
      least 20 cigarettes per day, or had at least 10 pack-years of smoking.

PMID- 15474754
TI  - Comparison of Estonian and Finnish physicians' opinions of menopause and hormone
      therapy.
AB  - OBJECTIVE: To compare Estonian and Finnish gynaecologists' and general
      practitioners' (GP) opinions on and prescribing practices in hormone treatment
      (HT) during and after menopause. METHODS: Data was collected using similar postal
      questionnaires. In 2000 in Estonia, a random sample included 212 gynaecologists
      and 288 GPs (68% responded); and in 1989 in Finland, 100 male and 100 female
      gynaecologists, 100 general practitioner specialists and 100 non-specialists (73%
      responded). Gynaecologists and GPs were compared to each other within the
      countries, and the two countries were compared within the specialities. RESULTS:
      Gynaecologists' opinions of benefits were positive and similar in Estonia and
      Finland, and more positive than those of GPs. Gynaecologists and GPs in both
      countries had similar opinions about harms. Gynaecologists were in favour of
      longer HT than GPs, and longer treatment was recommended in Finland than in
      Estonia. In both countries a large proportion of physicians (48% of
      gynaecologists in Estonia and 65% in Finland) stated that they would routinely
      prescribe HT to all women at menopause without contraindication, regardless of
      symptoms, and some (31% of gynaecologists in Estonia and 19% in Finland) favoured
      routine prescribing to all postmenopausal women. CONCLUSIONS: Estonian
      physicians' positive attitudes suggest increased use of HT. Comparisons of the
      two countries and specialities suggest that physicians' positive opinions may
      long predate increased use.

PMID- 15474755
TI  - Apoptosis, proliferation, and sex steroid receptors in postmenopausal endometrium
      before and during HRT.
AB  - OBJECTIVES: Endometrial homeostasis, indicated as the balance between apoptosis
      and proliferation, was studied with regard to endometrial safety and bleeding
      disturbances. MATERIALS AND METHODS: The quantitatively sufficient endometrial
      biopsies of 92 postmenopausal women enrolled in the study were investigated. The
      participants were divided into two groups, each receiving a continuous combined
      HRT regimen with either conjugated estrogen (CE) 0.625 mg + 5 mg
      medroxyprogesterone acetate (MPA) (=CE/MPA) or 17-beta-estradiol (E2) 2 mg + 1 mg
      norethisterone acetate (NETA) (=E2/NETA). These were evaluated according to
      apoptotic index (Ai) and proliferation marker Ki-67 index. Estrogen receptor
      alpha (ER) and progesterone receptor (PR) expression were also monitored, as well
      as endometrial thickness. Quantitative in situ techniques were used. RESULTS: Ai
      and Ki-67 index were unchanged in epithelial glands of endometrium from baseline
      to second biopsy obtained after 1 year of combined continuous HRT. In stromal
      tissue, Ki-67 index was increased, while Ai was on the same level. PR expression
      in both epithelium and stroma was unchanged. Endometrial thickness was unaffected
      during therapy, and the histopathological evaluation showed no development of
      hyperplasia or carcinoma. CONCLUSIONS: The unaffected homeostasis in endometrial
      epithelium contributes to endometrial safety and is in accordance with the
      histopathological findings of no hyperplasia. The homeostasis of stroma was
      transformed to be more proliferative. Increased stromal proliferation may be of
      importance for stromal support of the veins and for decreasing breakthrough
      bleeding during HRT. The increased stromal proliferation, as well as the
      decreased ER expression both in epithelium and stroma, could be an effect of
      progesterone.

PMID- 15474756
TI  - Endogenous estrogen levels affect sexual function in elderly post-menopausal
      women.
AB  - OBJECTIVE: The objective of this study was to determine if there is an
      association between endogenous serum concentration of estradiol (E2) and changes
      in sexual function in post-menopausal women over 3 years. METHODS: Sexually
      active women (N = 345, mean = 65 years) who participated in the multiple outcomes
      of raloxifene evaluation trial (MORE) had endogenous E2 levels measured at
      baseline. All women completed the sexual history questionnaire at baseline and 3
      years later. We assessed sexual function (desire, activity, feelings/experiences
      and sexual problems) among these women by endogenous E2 level (<20 pmol/l or > or
      =20 pmol/l). RESULTS: At baseline, women with E2 levels <20 pmol/l had
      significantly greater discomfort and inability to relax compared with women with
      E2 > or =20 pmol/l (P < 0.05 for all). After 3 years, women with E2 > or =20
      pmol/l had significantly less decline in sexual enjoyment (P < 0.02),
      satisfaction (P < 0.02), sexual comfort (P < 0.05) and sexual feelings summary
      score (P = 0.001), when compared with women who had E2 levels <20 pmol/l.
      CONCLUSIONS: Endogenous E2 levels are important predictors of change in sexual
      function in elderly women who are sexually active. However, this result needs to
      be proven in a study with a bigger sample size of sexually active women, who
      present with changes in sexual function over several years. Also, future
      investigations are needed to assess the effects of other endogenous hormones on
      sexual function in elderly women.

PMID- 15474757
TI  - Correlation between some metabolic markers of vascular risk and carotid artery
      intima-media thickness in postmenopausal women.
AB  - AIM AND SETTING: This study investigated correlations between insulinemia,
      insulin sensitivity, body mass index, lipids and lipoproteins with intima-media
      thickness in a group of 25 (age range 40-55 years) postmenopausal women (minimum
      duration of menopause 2 years) not on hormone replacement treatment. METHODOLOGY:
      Uni and multivariate correlations showed a direct relationship between insulin
      pattern, insulin sensitivity, body mass index, low density lipoproteins and
      increased intima-media thickness. RESULTS: Our multivariate correlation results
      revealed that intima-media thickness is influenced by the associations of the
      different metabolic functions investigated. Therefore, carotid wall intima-media
      thickness represents a dependent variable in postmenopausal women for some
      metabolisms whose dysfunction leads to atherosclerosis. CONCLUSION: This
      multielement synergy is able to detect cardiovascular risk and may underlie
      cardiovascular mortality in postmenopausal women.

PMID- 15474759
TI  - Age at natural menopause and cognition.
AB  - OBJECTIVES: To examine associations between age at natural menopause, childhood
      IQ and cognition at age 65 years. To determine if lower age at menopause partly
      mediates the effect of childhood IQ on cognition at age 65 years. METHODS: Data
      were provided by a sub-cohort of women participating in a longitudinal study of
      brain ageing and health. Main variables were childhood IQ from a 1947 national
      survey of children born in 1936, age at natural menopause and five cognitive
      tests measured in 2000-2001. RESULTS: Age at menopause was associated with
      childhood IQ (r = 0.221, P = 0.008) and with general cognitive function age 65
      years (r = 0.246, P = 0.004). Multiple regression showed 44.4% of the reliable
      variance in cognitive ability age 65 years is contributed by IQ at an age of 11
      years to which, years of education contributed an additional 3.9%. Structural
      equation modelling suggested that childhood IQ differences contribute 4.8% of the
      variance to age at natural menopause and that the relation between age at
      menopause and cognition at age 65 years was accounted for by childhood IQ.
      CONCLUSION: Childhood IQ and age at menopause each have significant relations
      with general cognitive function age 65 years but the link between cognition age
      65 years and age at menopause might be wholly explained by childhood IQ. The
      association between childhood IQ and age at menopause may be attributed to
      central neural mechanisms or, as argued here, to the effects of childhood IQ on
      adult general health.

PMID- 15474758
TI  - A short study in the treatment of hot flashes with buccal administration of 17
      beta estradiol.
AB  - OBJECTIVE: To assess the efficacy and safety of 17-beta estradiol buccal tablets
      in reducing hot flush frequency (HFF) in postmenopausal women. METHODS: Estradiol
      buccal tablets containing 0.05, 0.1, 0.2, or 0.4 mg or placebo were administered
      for 28 days to 99 postmenopausal women in a randomized, double-blind study; 19
      premenopausal women were studied concurrently for comparison of laboratory data.
      Objective and subjective assessments of HFF were obtained along with measures of
      estradiol, estrone, follicle-stimulating hormone (FSH), and luteinizing hormone
      (LH). RESULTS: Measurements of HFF revealed significant decreases from baseline
      in all estradiol groups (P < 0.01). In the 0.4 mg group, HFF decreased
      significantly compared to placebo (P < 0.01). All estradiol doses produced
      similar improvement in the vaginal maturation index. Mean serum estradiol levels
      increased as doses increased but were lower than in the premenopausal subjects.
      Mean serum FSH and LH levels decreased in all estradiol groups but not to the
      levels of the premenopausal subjects; the greatest decrease occurred at the two
      highest estradiol doses. CONCLUSION: A numerical dose-response relationship with
      hot flushes was seen in this pilot study comparing 0.05, 0.1, 0.2, and 0.4 mg
      buccal estradiol. Only 0.4 mg 17-beta estradiol significantly reduced the
      occurrence of hot flushes compared to placebo.

PMID- 15474760
TI  - The influence of Nos3 polymorphisms on age at menarche and natural menopause.
AB  - OBJECTIVE: Deficiency of the gene encoding endothelial nitric oxide synthase,
      i.e. Nos3, has been reported to be associated with late menarche, reduced
      ovulation rates, fewer deliveries, and earlier onset of menopause in a mouse
      model. METHODS: We assessed the Glu298Asp and the T-786C polymorphisms of Nos3 in
      87 consecutive healthy postmenopausal women by pyro- and capillary-sequencing,
      respectively. Results were correlated with age at menarche and natural menopause,
      number of miscarriages and live births, as well as body mass index (BMI) and
      smoking habits. RESULTS: Allelic frequencies of the Glu298Asp polymorphism of
      Nos3 were 121 (69.5%) and 53 (30.5%) for the wild-type G allele and the mutant T
      allele, respectively. Forty-one women (47.1%) were homozygote wild-type (G/G), 39
      (44.9%) were heterozygote (G/T), and 7 (8.0%) were homozygote mutant (T/T).
      Allelic frequencies of the T-786C polymorphism of Nos3 were 105 (60.6%) and 69
      (39.4%) for the wild-type T allele and the mutant C allele, respectively. Thirty
      three women (38.0%) were homozygote wild-type (T/T), 39 (45.1%) were heterozygote
      (T/C), and 15 (16.9%) were homozygote mutant (C/C). Presence of at least one
      mutant allele of the Glu298Asp or the T-786C polymorphisms of Nos3 were not
      associated with age at menarche, natural menopause, and number of miscarriages
      and deliveries. BMI above 27 kg/m2 and smoking were associated with earlier onset
      of natural menopause (47.8 years versus 50.2 years (P = 0.01) and 46.8 years
      versus 49.8 years (p = 0.02)). CONCLUSIONS: Our data show that smoking and
      increased BMI, but not Glu298Asp or the T-786C polymorphisms of Nos3, are
      associated with an early onset of natural menopause.

PMID- 15474761
TI  - The relationship of estrogen receptor-alpha polymorphism with symptoms and other
      characteristics in post-menopausal women.
AB  - OBJECTIVES: To study the influence of the estrogen receptor-alpha (ER-alpha)
      genotypes (PvuII and XbaI polymorphisms) on symptoms and bone density. METHODS:
      We recruited 177 post-menopausal women to register hot flashes, vaginal dryness,
      depression, anxiety, sleep alterations, and serum hormones (FSH, LH, estrone, and
      estradiol). Bone mineral density (BMD) was measured with a radiographic method,
      correcting with an external reference. ER-alpha genotyping was carried out by
      PCR. RESULTS: Scores for vaginal dryness were lower for the xx (P = 0.003), and
      pp genotypes (P = 0.006). Hot flashes were lower for the Pp (P = 0.006) genotype.
      FSH circulating levels were lower for Xx genotype (P = 0.036). The factors
      associated with BMD were estrone (P > 0.000001), estradiol (P = 0.0035) and XbaI
      (P = 0.035). Vaginal dryness, was associated with PvuII and XbaI polymorphisms (P
      = 0.037 and P = 0.039). Depression was associated with log(estrone) (P = 0.011),
      schooling (negatively, P = 0.012), and marginally with BMI (P = 0.066). Sleep
      alterations correlated with log(estrone) (P = 0.014) and marginally with years
      since menopause (P = 0.046). Anxiety correlated with schooling (negatively, P =
      0.006) and age (p = 0.015), and hot flashes with schooling (negatively, P =
      0.014). BMD was associated with log(estrone) (p < 0.000001), estradiol
      (negatively, P = 0.0036), and marginally with XbaI (P = 0.036). CONCLUSIONS: In
      post-menopausal women, the ER-alpha polymorphism was associated with vaginal
      dryness, and hot flashes but not with other physical or emotional symptoms.
      Extraglandular estrogen production, and diverse molecular factors related to
      estrogen action may play an important role in this process.

PMID- 15474762
TI  - Long-term hormone replacement therapy delays the age related progression of
      carotid intima-media thickness in healthy postmenopausal women.
AB  - OBJECTIVES: Carotid intima-media thickness (IMT) is an appropriate intermediate
      end point to investigate clinically relevant effects on atherogenesis. The study
      objective was to clarify whether long-term hormone replacement therapy (HRT)
      modifies the progress of age-related IMT in healthy postmenopausal Japanese
      women. METHODS: One hundred and eighty-eight healthy postmenopausal women aged 42
      69 years were recruited into the retrospective study. IMT was measured by B-mode
      real-time ultrasound in the following three groups of patients. One hundred and
      fifteen women who were prescribed estrogen plus progestin or estrogen alone were
      classified into two groups according to the HRT treated period: short-term (<2
      years of treatment, n = 52) and long-term (> or =2 years, n = 63) HRT groups. The
      third group consisted an age-matched women (n = 73), who were never treated with
      HRT (non-HRT group) as a control. RESULTS: Each group was divided into three
      subgroups according to age: < or =49 years, 50-59 years and 60 years or older.
      IMT in patients of age > or =60 years in the non-HRT group was 0.607 +/- 0.064 mm
      and was significantly higher compared with that in the other two age subgroups of
      non-HRT patients (< or =49 years: [0.495 +/- 0.051 mm; 50-59 years: 0.505 +/-
      0.068 mm) (P < 0.05). In the short-term HRT group, IMT of > or =60-year-old
      subjects (0.588 +/- 0.074 mm) was also significantly higher compared with that in
      the other two age subgroups (< or =49 years: 0.480 +/- 0.034 mm; 50-59 years:
      0.511 +/- 0.062 mm). However, in the long-term HRT group, IMT was not
      significantly different among the three age subgroups. There was a significant
      relationship between IMT and age in non-HRT (r = 0.594, P < 0.0001) and short
      term HRT (r = 0.542, P < 0.001) groups, but no significant relationship was
      observed in the long-term HRT (r = 0.195 , P = 0.1266) group. CONCLUSIONS: In
      long-term HRT, more than 2 years may delay the age-related increase in IMT in
      healthy postmenopausal Japanese women.

PMID- 15474764
TI  - Headaches in pregnancy.
AB  - Migraine and TTH are primary headache disorders that occur commonly during
      pregnancy. Migraine sometimes occurs for the first time with pregnancy. The
      majority of migraineurs improve while pregnant; however, migraine often recurs
      post partum. Some disorders that produce, headache, such as stroke, cerebral
      venous thrombosis, eclampsia, and SAH, occur more frequently during pregnancy.
      Diagnostic testing serves to exclude organic causes of headache, to confirm the
      diagnosis, and to establish a baseline before treatment. If neurodiagnostic
      testing is indicated, the study that provides the most information with the least
      fetal risk is the study of choice. Drugs commonly are used during pregnancy
      despite insufficient knowledge about their effects on the growing fetus. Most
      drugs are not teratogenic. Adverse effects, such as spontaneous abortion,
      developmental defects, and various postnatal effects, depend on the dosage and
      route of administration and the timing of the exposure relative to the period of
      fetal development. Although medication use should be limited, it is not
      absolutely contraindicated in pregnancy. In migraine, the risk for status
      migrainosus may be greater than the potential risk of the medication used to
      treat the pregnant patient. Nonpharmacologic treatment is the ideal solution;
      however, analgesics, such as acetaminophen and narcotics, can be used ona limited
      basis. Preventive therapy is a last resort.

PMID- 15474765
TI  - Multiple sclerosis and pregnancy.
AB  - Overall, evidence suggests the effect of pregnancy is at least neutral and
      possibly positive on the course of MS. The lack of effect MS has on pregnancy
      outcomes also is significant. In the end, pregnancy is an individual
      decision.Physicians, and in particular neurologists, play a key role in providing
      tools to assist women who are living with MS make the most appropriate decision
      concerning family planning for themselves and their families.

PMID- 15474766
TI  - Myasthenia gravis and pregnancy.
AB  - Treatment considerations for women who have MG and are of childbearing age are
      complicated. When possible, before pregnancy, establishing a plan for therapy is
      ideal, recognizing the potential concerns for the patient and the fetus.
      Decisions about treatment during pregnancy must balance the potential
      complications for the fetus, the patient, and even the integrity of the
      pregnancy. Most women who have MG are able to complete pregnancy successfully and
      deliver a healthy baby; however, there always is some risk that NMG may occur.
      Pregnant patients who have MG are served best at centers capable of providing
      coordinated expert care from neurologic, obstetric, and pediatric providers.

PMID- 15474767
TI  - Movement disorders in pregnancy.
AB  - Movement disorders are not particularly common during pregnancy, with a few
      exceptions. RLS occurs most commonly followed by CG. Currently, with the
      incidence of rheumatic fever lower than previously, any woman who develops CG
      should be checked for illness other than rheumatic heart disease. The
      differential includes systemic lupus erythromatosis and antiphospholipid antibody
      syndrome. Regarding the use of dopaminergic agents, the dopamine agonist,
      pergolide, can be maintained during pregnancy for the treatment of PD, Segawa
      disease, and RLS. The use of levodopa and ropinirole should be limited during
      pregnancy because of the possible teratogenic effects. Amantadine is
      contraindicated during pregnancy. The data on selegiline are controversial;
      animal studies show possible serotonergic effects and teratogenic effects. If
      treatment is indicated in patients who have Tourette syndrome, the high potency
      neuroleptics drugs (haloperidol) are preferred to treat associated symptoms.
      Depression is a common comorbidity in patients who have PD, HD,Tourette syndrome,
      or other chronic neurologic diseases. Depression treatment during pregnancy is
      covered by Levy et al elsewhere in this issue. As discussed previously, most of
      the data on the use of drugs during pregnancy, especially the dopaminergic
      agents, are limited to animal studies and case reports. Therefore, it is in part
      left to the neurologist to decide on treatment based on the individual patient,
      clinical judgment, and inferences from animal studies and limited case reports.

PMID- 15474768
TI  - Pregnancy in women who have epilepsy.
AB  - Ideal, comprehensive care of women who have epilepsy during the reproductive
      years must include effective preconceptional counseling and preparation. The
      importance of planned pregnancies with effective birth control should be
      emphasized, with consideration of the effects of the enzyme-inducing AEDs on
      lowering efficacy of hormonal contraceptive medications and the need for back-up
      barrier methods. Before pregnancy occurs, the patient's diagnosis and treatment
      regimen should be reassessed. Once the diagnosis of epilepsy is confirmed, it is
      important to verify if the individual patient continues to need medications and
      if she is taking the most appropriate AED to balance control of her seizures with
      teratogenic risks. For most women who have epilepsy, withdrawal of all AEDs
      before pregnancy is not a realistic option. A decision to undergo a trial while
      not taking AEDs before a planned pregnancy should be based on the same principles
      used for AED withdrawal in any person who has epilepsy. The taper should be
      completed at least 6 months before planned conception to provide some reassurance
      that seizures are not going to recur. If a woman who has epilepsy is in the more
      prevalent category of needing AEDs for seizure control, then monotherapy at the
      lowest effective dosage should be used. If large daily doses are needed, then
      frequent smaller doses or extended-release formulations may be helpful to avoid
      high peak levels. Some of the newest information about differential risks between
      AEDs also should be considered. The woman's AED regimen should be optimized and
      folate supplementation should begin before pregnancy. Given that 50% of
      pregnancies are unplanned in the United States, folate supplementation should be
      encouraged in all women of childbearing age who are taking any AED for any
      indication. Dosing recommendations vary from 0.4 mg/d to 5 mg/d. It is not
      uncommon for a physician to consider changing AED regimens when the patient first
      reports that she is pregnant. In many cases, she already is in or past the
      critical period of organogenesis (Table 3). If a woman who has epilepsy presents
      after conception and is taking a single AED that is effective, her medication
      usually should not be changed. Exposing the fetus to a second agent during a
      crossover period of AEDs only increases the teratogenic risk, and seizures are
      more likely to occur with any abrupt medication changes. If a woman is on
      polytherapy, it may be possible to switch to monotherapy safely. Seizure control
      remains an important goal during pregnancy. In particular, convulsive seizures
      place the mother and fetus at risk. Nonconvulsive seizures also may be harmful,
      especially if they involve falling or other forms of trauma. Monitoring serum AED
      levels during pregnancy can be helpful in optimizing seizure control. Prenatal
      screening can detect major malformations in the first and second trimesters.
      Vitamin K1 is given 10 mg/d orally during the last month of pregnancy followed by
      1 mg intramuscularly or intravenously to the new-born. Although women who have
      epilepsy and women who are taking AEDs for other indications do have increased
      risks for maternal and fetal complications, these risks can be reduced
      considerably with effective preconceptional planning and careful management
      during pregnancy and the postpartum period.

PMID- 15474769
TI  - Stroke in pregnancy.
AB  - Stroke in pregnancy and the puerperium is a rare but serious cause of maternal
      and fetal mortality. Pregnancy-associated maternal changes should remain
      additional considerations in the evaluation and treatment of the pregnant patient
      who has stroke and not preclude a comprehensive stroke evaluation. Instead, the
      approach to the pregnant patient who has stroke should include the evaluation of
      general causes of stroke in the young, with the additional consideration of the
      rare pregnancy-specific causes. Understanding the potential maternal and fetal
      risks of diagnostic testing and treatment is crucial to appropriate decision
      making when caring for the pregnant patient who has stroke.

PMID- 15474770
TI  - Neurologic aspects of eclampsia.
AB  - Eclampsia continues to be a significant cause of maternal and fetal death
      throughout the world. Neurologists have a specific role to play in the diagnosis
      and management of patients who have eclampsia, especially those who have
      recurrent seizures, raised intracranial pressure, and coma. Postpartum patients
      may be admitted to a neurology service when they present to the emergency
      department with seizures. The cornerstone of treatment has been blood pressure
      control and magnesium sulfate with its antivasospastic effect. Should this fail,
      antiepileptic drugs of proved efficacy, such as diazepam and phenytoin, can be
      used. Recent studies reveal genetic and mitochondrial defects in eclampsia, but
      further investigation is warranted to determine the complex underlying
      pathophysiologic interplay and the optimum prophylactic and therapeutic
      management.

PMID- 15474771
TI  - Psychiatric disorders in pregnancy.
AB  - This review, although not exhaustive, provides information on the potential
      impact of psychiatric illness on obstetric outcome. There is clear evidence that
      psychiatric illness poses a risk to pregnancy outcome. There productive safety
      data on many of the available treatments fail to demonstrate a clear risk from
      treatment. The medications with clear teratogenic, neonatal, and developmental
      risks are, not surprisingly, those used to treat some of the most severe and
      debilitating psychiatric illnesses. Even the amount of information available is
      inadequate without some straightforward clinical guidelines. A model of risk for
      illness and treatments of illnesses during pregnancy developed by the authors'
      group reminds clinicians that nonexposure does not exist. Rather, the decision is
      which type of exposure is in the best interest of the patient and family-exposure
      to illness or exposure to treatment. Regardless of the choice, clinicians are
      encouraged to think in terms of reducing the total number of exposures; that is,
      if choosing to treat, patients should be kept well by adjusting and monitoring
      medications-partial treatment simply provides exposure to illness and treatment.
      Guidelines to accomplish the goal of minimizing exposures include: 1. Treating
      women of reproductive capacity from the first visit as if they are pregnant:
      choosing treatments with reproductive safety information (eg, new and improved =
      no data) and providing supplemental folic acid for all women (800 microg), with
      higher doses for those treated with anticonvulsants (3 to 4 mg).2. For women who
      conceive while taking a medication, and if it was efficacious for them, then the
      majority of decisions for medication selection should be considered already made
      for pregnancy and lactation (eg, do not switch medications once pregnant or for
      breastfeeding, as that simply exposes the baby to a second medication and the
      data previously discussed do not apply). 3. Because the serum concentration of
      most medications decreases during pregnancy, establishing criteria a priori for
      increasing the maternal daily dose; as a general rule, sleep patterns are good
      markers of psychiatric illnesses. 4. Always preferring monotherapy to two
      medications. 5. Obtaining up-to-date information at www.emorywomensprogram.org (a
      website with links to many support groups, reproductive safety registries) or
      other women's health websites. These basic guidelines can help decrease the
      number of exposures and aid in conducting clinical care with at least some
      reproductive safety data.

PMID- 15474774
TI  - Myocarditis: emergency department recognition and management.
AB  - Myocarditis is an acute inflammatory syndrome involving the heart and related
      structures. In many instances, the presentation is obvious, and appropriate
      treatment and disposition follow accordingly. In other situations, patients
      present with viral illness of the respiratory or gastrointestinal tracts (or
      both) or nonspecific symptoms such as fatigue and weakness,leading the clinician
      astray. Management is largely supportive, including aggressive cardiorespiratory
      support.

PMID- 15474773
TI  - Deadly drug interactions in emergency medicine.
AB  - Many life-threatening drug interactions are predictable, avoidable events.
      Emergency medicine physicians have a responsibility to recognize and prevent drug
      interactions. Keeping current on the many pharmaceutical therapies,their
      pharmacology, and potential drug interactions currently represents one of the
      biggest challenges for emergency medicine practitioners. Using current drug
      interaction resources and knowing the limited number of medications that are
      responsible for the most serious drug interactions can ease this seemingly
      overwhelming burden greatly. Clinicians need to be particularly vigilant when
      prescribing drugs for patients who are taking medications with potential for drug
      interactions leading to serious consequences.

PMID- 15474775
TI  - Aortic disasters.
AB  - TAD and AAA are two of the highest risk disease entities in emergency medicine.
      Emergency physicians should be vigilant in their approach to patients who have
      symptoms compatible with acute aortic disease. In chest and abdominal pain
      presentations, the chart must look like there was a search for the TAD and AAA.
      By having a sound knowledge of atypical cases;, having an appreciation for how
      subtle TAD and AAA can be; and recording and documenting a thorough history,
      physical examination, and risk factor profile, the emergency physician may reduce
      substantially the risk of missing a diagnosis and subsequently being sued.
      Emergency physicians cannot diagnose every case of acute aortic disease; what
      they can do is practice with a sound understanding of risk management principles
      and consider these diagnoses in all patients with chest, back, or abdominal
      pain.Ultimately, this strategy would provide protection for the patient and the
      physician.

PMID- 15474776
TI  - Mesenteric ischemia.
AB  - MI remains a highly lethal entity. Improving survival requires an aggressive,
      multidisciplinary approach. High-risk patients with severe abdominal pain and a
      paucity of physical findings should be undergo emergent imaging in a search for
      this disease. Improvements in laboratory tests and advances in imaging techniques
      may improve the ability to diagnose MI earlier in its course, before irreversible
      damage has occurred. Many treatment modalities are available and should be
      tailored to each individual case. By recognizing and preventing ischemia
      reperfusion injury,the cycle of protracted complications may be broken. A
      decrease in the mortality from MI finally is occurring. Early recognition and
      aggressive treatment finally may allow clinicians to have a marked impact on
      patient survival.

PMID- 15474777
TI  - Unsuspected neonatal killers in emergency medicine.
AB  - A neonate presenting to the emergency department can present a challenge to even
      the most experienced clinician. This article has focused on four deceiving and
      potentially devastating neonatal diseases. 1. Neonatal herpes is a potentially
      devastating illness without pathognomonic signs or symptoms. Early recognition
      and therapy can reduce mortality markedly. Although no specific sign or symptom
      is diagnostic,the diagnosis should be strongly considered in the presence of HSV
      risk factors, atypical sepsis, unexplained acute hepatitis, or focal seizure
      activity. Acyclovir therapy should be initiated before viral dissemination or
      significant CNS replication occurs. 2. Pertussis is a disease in which infants
      are at greatest risk of death or severe complication. Neonatal pertussis often
      presents in an atypical manner, lacking the classic signs and symptoms such as
      the "whoop."More common signs and symptoms include cough, feeding difficulty,low
      grade fever, emesis, increasing respiratory distress, apnea, cyanosis,and
      seizures. Management should include hospitalization, supportive care, and
      antibiotics. 3. Congenital heart defects, particularly ductal-dependent lesions,
      may have an initial asymptomatic period that culminates in a rapidly progressive
      and fatal course. A neonate with CHD presents with shock refractory to volume
      resuscitation or pressor support. Resuscitative efforts are ineffective unless
      PGE, is administered. 4. Inborn errors of metabolism often are unsuspected
      because of their protean and heterogeneous nature. Signs and symptoms are
      subtle,are nonspecific, and often mimic other, more common diseases.An elevated
      index of suspicion, along with application and correct interpretation of a select
      few laboratory tests, is the key to making a diagnosis. Therapy is relatively
      straightforward and focused on resuscitation followed by prevention of catabolism
      and correction of specifically identified abnormalities. Although these disorders
      are relatively uncommon, prompt diagnosis and therapy can lead to a decrease in
      morbidity and mortality. The key is to maintain a high index of suspicion.

PMID- 15474778
TI  - Pulmonary embolism: an unsuspected killer.
AB  - The presentation of PE is often subtle and may mimic other diseases. Many
      pulmonary emboli invariably preclude diagnosis by their occult nature or by
      leading to rapid death from cardiopulmonary arrest. In patients who do manifest
      symptoms from PE, accurate diagnosis is essential. Often it is difficult to
      distinguish the vague symptoms of PE from other diagnoses, such as acute coronary
      syndrome, pneumonia, COPD, CHF,aortic dissection, myocarditis or pericarditis,
      pneumothorax, and musculo-skeletal or gastrointestinal causes. Regardless of the
      presentation, the most fundamental step in making the diagnosis of PE is first to
      consider it. Historical clues and risk factors should raise the clinician's
      suspicion.PE is an unsuspected killer with a nebulous presentation and high
      mortality. In all likelihood, PE will remain an elusive diagnosis despite
      advances in technology and a wealth of research. A high index of suspicion is
      required, but no amount of suspicion would eliminate all missed cases. Patients
      with significant underlying cardiopulmonary disease seem to be the most
      challenging. Patients with significant comorbidity have poor reserve and are
      likely to have poor outcomes, especially if the diagnosis is not made and
      anticoagulation is not initiated early. Controversy exists over the best
      diagnostic approach to PE. A battery of diagnostic studies is available, with few
      providing definitive answers. Studies such as CT may be helpful at some
      institutions but offer poor predictive value at others. Other diagnostic tests
      are not universally available. It is hoped that further research and improvements
      in current diagnostic modalities will clear some of the current confusion and
      controversy of this ubiquitous and deadly disease.

PMID- 15474779
TI  - Carbon monoxide poisoning.
AB  - CO is an insidious poison with many sources of exposure. CO poisoning produces
      diverse signs and symptoms, which often are subtle and can be misdiagnosed
      easily. Failure to diagnose CO poisoning may result insignificant morbidity and
      mortality and allow continued exposure to a dangerous environment. In the ED, a
      high index of suspicion must be maintained for occult CO exposure. Headache,
      particularly when associated with certain environments, and flulike illness in
      the wintertime with symptomatic cohabitants should raise the index of suspicion
      in the ED significantly for occult CO poisoning. Emergency treatment of CO
      poisoning begins with inhalation of supplemental oxygen and aggressive supportive
      care. HBOT accelerates dissociation of CO from hemoglobin and may prevent DNS.
      Absolute indications for HBOT for CO poisoning remain controversial, although
      most would agree that HBOT is indicated in patients who are comatose, are
      neurologically abnormal, have a history of loss of consciousness with their
      exposure, or have cardiac dysfunction. Pregnancy with an elevated CO-Hgb level
      (>15-20%) also is widely considered an indication for treatment. HBOT may be
      considered in patients who have persistent symptoms despite NBO, metabolic
      acidosis, abnormalities on neuropsychometric testing, or significantly elevated
      levels. The ideal regimen of oxygen therapy has yet to be determined, and
      significant controversy exists regarding HBOT protocols. The emergency physician
      may be confronted with the difficult decision regarding disposition and even
      transfer to a hyperbaric facility. Often the local medical toxicologist, poison
      control center, or hyperbaric unit can assist the emergency physician with the
      decision-making process.

PMID- 15474780
TI  - Deadly pediatric poisons: nine common agents that kill at low doses.
AB  - More than 97% of pediatric exposures reported to the AAPCC in 2001 had either no
      effect or mild clinical effects. Despite the large number of exposures, only 26
      of the 1074 reported fatalities occurred in children younger than age 6. These
      findings reflect the fact that, in contrast to adolescent or adult ingestions,
      pediatric ingestions are unintentional events secondary to development of
      exploration behaviors and the tendency to place objects in the mouth. Ingested
      substances typically are nontoxic or ingested in such small quantities that
      toxicity would not be expected. As a result, it commonly is believed that
      ingestion of one or two tablets by a toddler is a benign act and not expected to
      produce any consequential toxicity. Select agents have the potential to produce
      profound toxicity and death, however, despite the ingestion of only one or two
      tablets or sips. Although proven antidotes are a valuable resource, their value
      is diminished if risk after ingestion is not adequately appreciated and assessed.
      Future research into low-dose, high-risk exposures should be directed toward
      further clarification of risk, improvements in overall management strategies,and,
      perhaps most importantly, prevention of toxic exposure through parental education
      and appropriate safety legislation.

PMID- 15474781
TI  - Deadly viral syndrome mimics.
AB  - Upper respiratory tract infections (ie, "the common cold") have several hundred
      causes, the most common of which include rhino-virus, coronavirus, and
      respiratory syncytial virus. The clinical presentation varies with symptoms.
      Every emergency department, no matter what the demographics, cares for patients
      with this constellation of symptoms. Emergency physicians examine, diagnose, and
      treat these disorders frequently. With increasing burdens being placed on
      emergency physicians, it is possible to assume a diagnosis of upper respiratory
      tract infection without generating a complete differential diagnosis. The
      challenge is to identify and recognize the distinctions between an innocuous
      upper respiratory tract infection and a life-threatening disease "mimic" or
      entities. This article discusses some of these life-threatening mimics.

PMID- 15474782
TI  - Unsuspected internal organ traumatic injuries.
AB  - Emergency medicine physicians can avoid missed traumatic intra-abdominal injury
      by adopting a paradigm for patient evaluation that recognizes the patterns of
      injury associated with pathology, the importance of positive and negative
      physical findings, and the limitations of diagnostic studies. The burden of
      avoiding missed traumatic injuries does not rest with emergency medicine
      physicians alone, however. A missed diagnosis may be the result of a medical
      error involving multiple systems and individuals.Ultimately, decreasing the
      incidence of missed traumatic injury is an opportunity for quality improvement
      for all practitioners involved in the care of patients with trauma.

PMID- 15474783
TI  - Unsuspected vascular trauma: blunt arterial injuries.
AB  - Blunt arterial injury provides a tremendous challenge to the emergency physician
      and traumatologist. The overall incidence of these injuries, even with more
      modern and aggressive screening, is low. Often, they are clinically occult on
      initial presentation, and untreated, they frequently result in devastating
      consequences. Great potential exists, however, for averting these deadly
      consequences by recognizing patterns of injury, prompting expedient diagnosis by
      rapidly obtaining the appropriate diagnostic study and providing opportunity for
      specific therapy under the direction of the trauma surgeon.

PMID- 15474784
TI  - Rapid infectious killers.
AB  - Central to the practice of emergency medicine is the ability to identify patients
      in whom immediate intervention is needed to prevent long-term morbidity and
      mortality. This article has highlighted some of the characteristics of several
      infectious diseases that may become fatal quickly if not treated quickly and
      appropriately by physicians. Bacterial meningitis,necrotizing soft tissue
      infections, invasive gram-negative disease, pneumo-coccal pneumonia, and West
      Nile encephalitis all require prompt recognition and treatment by emergency care
      providers.

PMID- 15474785
TI  - Domestic violence: an approach to identification and intervention.
AB  - DV encompasses a wide variety of actions that coerce, control, or demean the
      victim. Victims of DV suffer many physical and mental health consequences that
      cause emergency physicians to encounter them knowingly or unknowingly in the
      medical setting. Physicians who are aware of the prevalent problem of DV are able
      to help victims the most. A physician should be educated to recognize the
      physical and emotional presentations of victims, but, more importantly, the
      physician should be knowledgeable about the need for screening of all patients to
      reach the greatest number of victims. Victims often are not ready or able to
      disclose DV because of patient and physician barriers. Clinicians should work to
      overcome these barriers by initiating screening, ensuring patient comfort and
      safety, and understanding the many stages involved in behavioral change that a
      victim must traverse. The emergency physician would experience less frustration
      and more success if he or she would change their role from problem solver to
      listener and empowerer. This approach allows the survivor to make informed
      choices. Patients who are ready to make changes must be provided with
      protection,treatment, resources, and support. Informed, active physicians have
      great potential for improving DV victims' lives, reducing the effects of
      violence,and facilitating the patient's progression from victim to survivor.

PMID- 15474787
TI  - Measuring surgical outcomes.

PMID- 15474788
TI  - Diffuse lamellar keratitis, endotoxin, and ophthalmic sponges.

PMID- 15474789
TI  - One string attached: preventing wick retention.

PMID- 15474790
TI  - Sponge use and mydriatic medications.

PMID- 15474793
TI  - Intracameral vancomycin and endophthalmitis prophylaxis.

PMID- 15474794
TI  - Capsulotomy diameter mark.

PMID- 15474796
TI  - Adjusting intraocular lens power for sulcus fixation.

PMID- 15474797
TI  - Digital video in a surgical setting.

PMID- 15474798
TI  - Bilateral keratectasia after unilateral laser in situ keratomileusis.

PMID- 15474799
TI  - Trypan blue in pediatric cataract surgery.

PMID- 15474800
TI  - A-constant and intraocular lenses.

PMID- 15474801
TI  - Consultation section. Cataract surgical problem.

PMID- 15474811
TI  - Phaco rolling technique.
AB  - We describe a phacoemulsification technique for soft and medium-hard cataracts to
      decrease phaco time and enhance the safety of the procedure. After conventional
      hydrodissection and hydrodelamination are performed, a 15- or 30-degree phaco tip
      is positioned on the peripheral lens beside the capsulorhexis edge and in contact
      with the nucleus-epinucleus interface. The lens is then aspirated onto the phaco
      tip. Phacoemulsification is started with the ultrasound energy level limited to
      15% to 25% depending on the nuclear hardness and with linear aspiration power up
      to 250 mmHg. The phaco tip is slightly displaced to the vertex of the pupil to
      keep it occluded, and the lens is rotated. The phaco tip is placed in the same
      area and a modified manipulator used to keep the lens in a horizontal position
      during rotational movement. The small, hard, central nucleus is usually
      emulsified at the end.

PMID- 15474812
TI  - Crystalline lens capsule staining with trypan blue.
AB  - A 1-step method for staining the anterior lens capsule with trypan blue is
      described. The dye is instilled via a paracentesis port at the start of cataract
      extraction. As aqueous humor is allowed to exit the anterior chamber (AC), which
      consequently shallows, the resulting pupil block confines the dye to the AC. An
      ophthalmic viscosurgical device (OVD) is used to flush dye-stained aqueous from
      the AC, circumventing the need for AC washout. Although the OVD may be tinged
      with dye, this does not impede performing capsulorhexis. This method does not add
      to the surgical time, requires no additional instruments or materials, and is
      safe.

PMID- 15474813
TI  - Primary viscocanalostomy versus trabeculectomy for primary open-angle glaucoma:
      three-year prospective randomized clinical trial.
AB  - PURPOSE: To compare the efficacy and safety of viscocanalostomy and
      trabeculectomy in patients with primary open-angle glaucoma (POAG). SETTING:
      Department of Ophthalmology, Ankara Education and Research Hospital, Ankara,
      Turkey. METHODS: In this prospective randomized trial, 50 eyes of 50 patients
      with medically uncontrolled POAG were randomized to have a trabeculectomy (25
      eyes) or a viscocanalostomy (25 eyes). Visual acuity, intraocular pressure (IOP),
      and slitlamp examinations were performed before surgery and 1 day, 1 week, 1, 3,
      and 6 months, and 1, 2, and 3 years postoperatively. RESULTS: At 3 years, the
      mean IOP was 16.0 mmHg +/- 7.07 (SD) in the trabeculectomy group and 17.8 +/- 4.6
      mmHg in the viscocanalostomy group (P=.694). Complete success (IOP 6 to 21 mm Hg
      without medication) was achieved in 66.2% of eyes at 6 months and 55.1% at 3
      years in the trabeculectomy group and in 52.9% and 35.3%, respectively, in the
      viscocanalostomy group (P>.05). Qualified success (IOP 6 to 21 mmHg with
      medication) was achieved in 95.8% of eyes at 6 months and 79.2% at 3 years in the
      trabeculectomy group and in 90.7% and 73.9%, respectively, in the
      viscocanalostomy group (P>.05). Postoperative hypotony and cataract formation
      occurred more frequently in the trabeculectomy group than in the viscocanalostomy
      group (P=.002). CONCLUSIONS: Primary trabeculectomy lowered IOP more than
      viscocanalostomy in POAG patients. However, the complication rate was lower in
      the viscocanalostomy group.

PMID- 15474814
TI  - POCOman: new system for quantifying posterior capsule opacification.
AB  - PURPOSE: To describe a new method of measuring posterior capsule opacification
      (PCO) and intraocular lens (IOL) rotation and report the validation of the
      method. SETTING: Ophthalmology Department, St. Thomas' Hospital, and Medical
      Imaging, Department of Physics, King's College, London, United Kingdom. METHOD: A
      new interactive software program, POCOman, was developed for the semiobjective
      assessment of PCO. Digital images of the posterior capsule, which can be acquired
      by any technique, are analyzed by the observer to determine the percentage area
      of PCO and assign a severity score. The system was validated by comparing it to
      clinical slitlamp evaluation of PCO and automated POCO system analysis using a
      library of 100 images taken from archives. The software also measures sequential
      IOL rotation for the evaluation of toric IOLs. RESULTS: An image could be
      analyzed in approximately 2 minutes. The results of the POCOman system correlated
      well with the results of the automated POCO system and clinical evaluation.
      CONCLUSIONS: The POCOman is an effective, user-friendly system for quantifying
      PCO. It can be obtained for free and has advantages over other methods.

PMID- 15474815
TI  - Adverse clinical consequences of neodymium:YAG laser treatment of posterior
      capsule opacification.
AB  - PURPOSE: To evaluate the clinical consequences of complications from
      neodymium:YAG (Nd:YAG) laser capsulotomy for posterior capsule opacification
      (PCO) over the lives of cataract patients. SETTING: CHU de Caen, Caen, France.
      METHODS: A model was constructed to estimate the lifetime clinical consequences
      of postoperative PCO treated by Nd:YAG laser capsulotomy. The probability of
      death was modeled from French mortality tables as a polynomial function of sex
      and age. The probability of becoming blind was modeled as a function of age from
      data in the literature. The incidence of Nd:YAG complications came from the
      literature. The rate of Nd:YAG capsulotomy over time was modeled as a survival
      curve using data from a cohort of 3335 patients. RESULTS: Over 9 years in a 70
      year-old population, switching from an IOL with a 20% Nd:YAG capsulotomy rate at
      3 years to an IOL with a 5% rate would avoid 1 chronic intraocular pressure
      increase requiring medical follow-up in every 54 surgeries, 1 case of glaucoma in
      every 237 surgeries, 1 case of cystoid macular edema in every 265 surgeries, and
      1 retinal detachment in every 265 surgeries. A 3-year clinical study would only
      capture one-third to one-half of long-term adverse events of Nd:YAG capsulotomy.
      CONCLUSION: Reducing PCO and the associated use Nd:YAG laser capsulotomy may
      contribute to preserving visual acuity in patients over their lifetimes.

PMID- 15474816
TI  - Phacoemulsification with intraocular lens implantation in cases of pars planitis.
AB  - PURPOSE: To analyze the results of phacoemulsification cataract surgery with
      implantation of posterior chamber intraocular lenses (IOLs) of different
      biomaterials in eyes with pars planitis. SETTING: Medical and Vision Research
      Foundations, Sankara Nethralaya, Chennai, India. METHODS: The records of 86
      patients (100 eyes) with pars planitis who had phacoemulsification with IOL
      implantation between January 1997 and April 2003 were retrospectively analyzed.
      The eyes were divided into 3 groups depending on IOL biomaterial: poly(methyl
      methacrylate) (PMMA) (n=32), heparin-surface-modified PMMA (n=39), or acrylic
      (n=29). The postoperative visual outcome and complications in each group were
      analyzed. RESULTS: Forty-seven patients were men and 39, women. The mean age was
      38 years (range 10 to 65 years) and the mean follow-up, 19.67 months (range 3.00
      to 54.53 months). At the final follow-up, 91 eyes (91%) had better visual acuity
      than preoperatively; 79 had an improvement of 2 or more Snellen lines, 12 had an
      improvement of 1 Snellen line, 4 had no change, and 5 had a decrease as a result
      of reactivation of the pars planitis and progression of cystoid macular edema
      (CME). Significant posterior capsule opacification occurred in 10 eyes (10%), CME
      in 50 eyes (50%), reactivation of pars planitis in 51 eyes (51%), IOL deposits in
      29 eyes (29%), IOL decentration in 1 eye (1%), and anterior capsule fibrosis in
      14 eyes (14%). The most frequent cause of poor visual recovery was CME,
      submacular fibrosis, and epiretinal membrane. There was no statistically
      significant difference in these complications between the 3 groups. CONCLUSIONS:
      Phacoemulsification with IOL implantation in eyes with pars planitis was safe and
      led to good visual outcomes in most cases. The factors in surgical success were
      control of inflammation, meticulous surgery, in-the-bag IOL implantation, and
      vigilant postoperative care.

PMID- 15474817
TI  - Predicting postoperative intraocular lens position and refraction.
AB  - PURPOSE: To predict the postoperative IOL position and refraction as accurately
      as possible independent of individualization of the parameters. SETTING:
      Universitats-Augenklinik, Mainz, Germany, and Vienna, Austria. METHODS: One
      patient cohort (189 eyes, Vienna) was used to calibrate the prediction method,
      which was then applied to a second cohort (65 eyes, Mainz). All calculations were
      based on consistent numerical ray tracing of the pseudophakic eye using the
      original manufacturer's intraocular lens (IOL) data (radii, thickness, refractive
      index). A new algorithm to predict IOL position was developed. Ultrasound (US)
      axial lengths were calibrated relative to partial coherence interferometry (PCI).
      Corneal radii extracted from topography were checked against radii measured with
      the IOLMaster (Zeiss) and by Littmann keratometry. RESULTS: Zero mean prediction
      errors for IOL position and refraction were obtained without adjusting the
      parameters and with PCI lengths or US lengths calibrated relative to the PCI
      values. There was no significant loss of accuracy of US data compared to PCI
      data. Corneal radii extracted from topography were slightly but statistically
      significantly different from the Littmann values, and they were more accurate
      than the latter with respect to prediction error. The measured mean central IOL
      position (distance from posterior corneal surface) for all IOL types was 4.580
      mm, a value very close to the mean recalculated from A-constants (4.587 mm). The
      difference in the individual central IOL position relative to the mean value
      depended only linearly (ie, no higher orders such as square or cubic are needed)
      on axial length, with the mean central IOL position as a free parameter. This
      parameter should be 4.6 +/- 0.2 mm (the same value as independently measured or
      recalculated) to obtain zero steepness of the prediction error as a function of
      axial length, producing zero bias for long and short eyes. CONCLUSIONS:
      Calculation errors from formulas and confusing adjusting parameters can be
      avoided if calculations and measurements are performed on a clear and simple
      physical basis. Nevertheless, an individual prediction error, typically 0.5 to
      1.0 diopter, seems to be unavoidable.

PMID- 15474818
TI  - Optical formula to predict outcomes after implantation of accommodating
      intraocular lenses.
AB  - PURPOSE: To analyze the effect of optical parameters on the outcomes of
      accommodating intraocular lens (IOL) implantation in cataract surgery. SETTING:
      Department of Ophthalmology, KULeuven University, Leuven, Belgium. METHODS: Thin
      lens approximation optics were used to obtain a formula containing the following
      variables: axial length (AL), mean keratometry (Km), anterior chamber depth
      (ACD), and presumed anterior shift of the IOL (dACD). The influence of these
      variables was separately analyzed. RESULTS: The accommodative amplitude (AA)
      decreased with a longer AL and higher Km. The AA varied between -5.4 diopters (D)
      and 0.0 D in eyes with an AL between 20.0 mm and 28.0 mm and a Km between 38.0 D
      and 52.00 D. The dACD was also a significant factor influencing the AA. The ACD
      had less influence on the AA. CONCLUSION: The obtained formula could guide
      selection of candidates for accommodating IOL implantation.

PMID- 15474819
TI  - Functional vision after cataract removal with multifocal and accommodating
      intraocular lens implantation: prospective comparative evaluation of Array
      multifocal and 1CU accommodating lenses.
AB  - PURPOSE: To compare the efficacy (functional vision, spectacle dependence) of the
      Array multifocal intraocular lens (IOL) (Advanced Medical Optics) and the 1CU
      accommodating IOL (HumanOptics AG). SETTING: Hartswood Hospital, Brentwood,
      United Kingdom. METHODS: This prospective study comprised patients scheduled to
      have standard phacoemulsification surgery with IOL implantation. Patients
      expressing a preference for spectacle independence were allocated to the Array
      multifocal IOL group. Those expressing no preference received the 1CU
      accommodating IOL. Efficacy measures included distance and near uncorrected
      visual acuity (UCVA), dynamic retinoscopy, and patient-reported spectacle
      independence. RESULTS: Seventeen patients (34 eyes) had bilateral implantation of
      the Array multifocal IOL, and 5 patients (9 eyes) had implantation of the 1CU
      accommodating IOL. Six to 18 months after surgery, 82.4% of eyes in the
      multifocal IOL group and 77.8% in the accommodating IOL group achieved a distance
      UCVA of 20/20 (Snellen) or better; the difference between groups was not
      significant. However, a significantly greater proportion in the multifocal IOL
      group than in the accommodating IOL group (76.5% versus 44.4%) achieved a near
      UCVA of N5 (Snellen 20/40) or better (P=.0068). Sixteen patients (94.1%) with
      Array IOLs and 2 patients (50.0%) with 1CU IOLs reported spectacle independence.
      Dynamic retinoscopy showed that the mean accommodative effect in the 1CU group
      was 0.44 diopter. CONCLUSIONS: In this single-surgeon single-site study, a
      greater proportion of Array multifocal IOL recipients than 1CU IOL recipients
      achieved functional near visual acuity. Only 1 patient with an Array IOL required
      corrective spectacles at the last visit.

PMID- 15474820
TI  - Phakic intraocular lens implantation versus clear lens extraction in highly
      myopic eyes of 30- to 50-year-old patients.
AB  - PURPOSE: To compare the outcome of treatment for myopia by phakic intraocular
      lens (IOL) implantation or by clear lens extraction (CLE). SETTING: Service
      d'Ophtalmologie, Hopital Purpan, Toulouse, France. METHODS: Thirty-nine patients
      from 32 to 49 years of age were studied. Forty-one eyes of 21 patients received a
      phakic IOL, and 36 eyes of 18 patients had phacoemulsification of the crystalline
      lens. The mean preoperative spherical equivalent (SE) was -13.6 diopters (D) +/-
      3.0 (SD) in the phakic IOL group and -16.7 +/- 3.8 D in the CLE group. RESULTS:
      Postoperatively, the mean SE was -1.06 +/- 0.78 D in the IOL group and -1.88 +/-
      0.83 D in the CLE group. At 12 months, the best corrected visual acuity (BCVA)
      had improved in 78.0% of eyes in the IOL group and 83.3% in the CLE group; no eye
      lost 1 line of BCVA. In 3 eyes (7.31%) in the IOL group, opacification of the
      crystalline lens developed 34, 36, and 44 months after implantation. Visual
      recovery after phacoemulsification was excellent. No eye in this group lost 1 or
      more lines of BCVA between 1 and 4 years of the initial surgery. In the CLE
      group, a retinal detachment occurred in 2 eyes at 39 and 43 months. The final
      BCVA in these eyes was counting fingers and 20/200. CONCLUSION: Implantation of a
      phakic IOL in a highly myopic eye of a patient between 30 and 50 years of age can
      be considered an adequate technique with a lower risk for loss of BCVA than CLE.

PMID- 15474821
TI  - Morphology of and visual performance with posterior subcapsular cataract.
AB  - PURPOSE: To study the prevalence and clinical profile of etiologically diverse
      posterior subcapsular cataracts (PSCs) and their effect on visual performance.
      SETTING: Iladevi Cataract & IOL Research Centre, Ahmedabad, India. METHODS: This
      prospective observational study comprised 160 eyes of 100 consecutive patients
      with PSC. Exclusion criteria included cortical opacities, cataract other than
      PSC, and a nondilating pupil. Lenticular changes such as gross appearance,
      density of opacity in the central 7.0 mm, and location and approximate area of
      cataract involvement were noted. The uncorrected distance and near acuities, best
      corrected visual acuity (BCVA), contrast sensitivity with BCVA, and history of
      glare were recorded. RESULTS: Sixty patients had bilateral PSC. The most
      prevalent cataracts were of unknown etiology (32.5%). The most common coexisting
      disease or factor was atopy (30.6%). Others were myopia, steroid use, diabetes,
      uveitis, retinitis pigmentosa (RP), glaucoma, and trauma. Most patients (47.0%)
      were 41 to 50 years old. The PSC was vacuolar in 45.0% of eyes, solid in 15.6%,
      and mixed in 39.4%. Vacuolar PSC was the most common type in the myopia,
      diabetes, RP, and trauma groups. Solid PSC was seen with myopia, diabetes, and
      glaucoma. Mixed PSC was the most common type in the steroid, atopy, uveitis, and
      idiopathic groups. Eighty-seven percent of patients had reduced visual acuity;
      76%, glare; and 46%, decreased contrast sensitivity. More eyes with vacuolar PSC
      had decreased visual acuity and contrast sensitivity, followed by eyes with solid
      PSC and eyes with mixed PSC. CONCLUSIONS: Most PSCs were of unknown etiology; a
      significant number of eyes had more than 1 etiology. Vacuolar PSC was the most
      common type, with more eyes in this group having significantly reduced visual
      acuity and contrast sensitivity. Specific morphological patterns occurred with
      some conditions (eg, RP, myopia, diabetes).

PMID- 15474822
TI  - Postoperative aphakia in modern cataract surgery: part 1: analysis of incidence
      and risks based on 5-year data from the Swedish National Cataract Register.
AB  - PURPOSE: To study the incidence of aphakia after cataract extraction and evaluate
      the relative risk for this outcome in subgroups of patients based on preoperative
      conditions. SETTING: Sixty-two community-run or private clinics participating in
      the Swedish National Cataract Register. METHODS: Data on cataract extractions
      were collected prospectively from 1997 through 2001. The set of data also covered
      type of surgery and type of intraocular lens (IOL), including a "no lens
      implanted" option. All data were stored in a database. Database calculations were
      made of frequencies and risk ratios of postoperative aphakia in the subgroups of
      patients based on preoperative conditions. RESULTS: For the entire study period,
      postoperative aphakia was reported in 1410 of 287,951 surgeries for which
      complete IOL data were available, corresponding to an overall frequency of 0.49%.
      The occurrence of ocular comorbidity and poor preoperative visual acuity (< or =
      0.1) in the eye to be operated on was significantly related to postoperative
      aphakia for each year of the study (P<.001). Glaucoma and poor visual acuity (<
      or =0.1) in the surgical eye meant a 12.8 higher risk for aphakia after surgery
      than a better visual acuity (>0.1) and no ocular comorbidity. CONCLUSIONS: This
      national 5-year survey showed that in routine cataract surgery performed during
      the study, 1 of every 200 operations ended in postoperative aphakia. Poor visual
      acuity (< or =0.1) in the eye to be operated on combined with ocular comorbidity
      was the highest risk factor for postoperative aphakia.

PMID- 15474823
TI  - Postoperative aphakia in modern cataract surgery: part 2: detailed analysis of
      the cause of aphakia and the visual outcome.
AB  - PURPOSE: To study the incidence of aphakia after cataract surgery, the surgical
      complications that can lead to it, and the visual outcome. SETTING: Six community
      run eye clinics participating in the Swedish National Cataract Register. METHODS:
      Data on cataract extractions were collected prospectively from 1997 through 2001.
      The data also covered the type of surgery and type of intraocular lens, including
      a "no lens implanted" option. All data were stored in a database. These data were
      supplemented with data on the intended type of surgery, type of complications,
      possible second surgery, and visual outcome. RESULTS: The overall incidence of
      postoperative aphakia was 0.65%. In 87.1% of cases, the aphakia was not planned,
      corresponding to an incidence of 0.48%. Unplanned aphakia was significantly
      related to poor preoperative vision, old age, and the presence of ocular
      comorbidity. The most frequent reasons for unplanned aphakia were intraoperative
      capsule problems and vitreous loss. In two thirds of cases, a second operation
      was performed. In 41% of all cases, the final visual acuity was 0.5 or better and
      in 27.7%, worse than 0.1. CONCLUSIONS: During the study period, 1 of every 200
      routine cataract surgeries ended in unplanned aphakia. The incidence of surgical
      complications leading to unplanned aphakia and a final visual acuity worse than
      0.1 (20/200) was 7.8 per 10,000 operations in cases with no ocular comorbidity
      and 27.6 per 10,000 operations in cases with ocular comorbidity.

PMID- 15474824
TI  - Correlation of infrared pupillometers and CCD-camera imaging from aberrometry and
      videokeratography for determining scotopic pupil size.
AB  - PURPOSE: To compare 2 infrared pupillometers with a videokeratographer and 2
      aberrometers for the determination of scotopic pupil size. SETTING: Department of
      Ophthalmology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
      METHODS: The pupil diameter was measured in 100 eyes of 51 patients after 2
      minutes of dark adaptation using the following devices: digital infrared
      pupillometer (Procyon Instruments Ltd.), handheld infrared pupillometer (Colvard)
      (Oasis Medical), Zywave aberrometer (Bausch & Lomb), Wasca aberrometer (Asclepion
      Meditec-Zeiss), and Orbscan II topography system (Bausch & Lomb Surgical).
      Measurements taken with the Procyon pupillometer were considered reference values
      for comparison with the other devices. Statistical evaluation was performed using
      the Bland-Altmann method for comparison of measurement techniques. RESULTS: The
      mean pupil size was 6.10 mm +/- 0.86 (SD) with the Procyon pupillometer, 5.68 +/-
      1.07 mm with the Colvard pupillometer, 5.91 +/- 1.01 mm with the Zywave
      aberrometer with the fixating target turned off, 5.09 +/- 1.14 mm with the Zywave
      aberrometer with the fixating target turned on, 5.59 +/- 0.99 mm with the Wasca
      aberrometer, and 3.75 +/- 0.67 mm with the Orbscan topographer. The limits of
      agreement were smallest for measurements between Procyon and Colvard and largest
      for measurements between Procyon and Orbscan. The sign test revealed
      statistically significant differences for all devices compared with the Procyon
      pupillometer (P<.001 in all cases) except the Zywave aberrometer with the
      fixating target turned off (P=.13). CONCLUSIONS: The Zywave wavefront sensor with
      the fixating target turned off using the study settings and light conditions
      provided measurements of scotopic pupil diameter that were closest to the
      reference values (Procyon). With the other devices (Colvard pupillometer, Zywave
      aberrometer with the fixating target switched on, Wasca aberrometer, and Orbscan
      topographer), the difference was statistically significant.

PMID- 15474825
TI  - Laser in situ keratomileusis for high hyperopia in awake, autofixating pediatric
      and adolescent patients with fully or partially accommodative esotropia.
AB  - PURPOSE: To establish the safety and efficacy of laser in situ keratomileusis
      (LASIK) in pediatric and adolescent patients with bilateral visual acuity of
      20/30 or better and accommodative or partially accommodative esotropia. SETTING:
      Department of Ophthalmology and Visual Science, University of Texas-Houston
      Medical School, Houston, Texas, USA. METHODS: The study comprised 30 eyes of 15
      consecutive patients with accommodative or partially accommodative esotropia who
      met eligibility requirements and had bilateral LASIK using the Alcon Summit
      Autonomous LADARVision excimer laser to correct a refractive error after January
      2001. All patients were awake and autofixating during the procedure. RESULTS: The
      mean age of the patients was 13.9 years (range 9.1 to 18.8 years) and the mean
      refractive error, +5.35 diopters (D) (range +3.75 to +8.50 D) with anisometropia
      of 2.0 D or less. The mean follow-up was 15.7 months (range 9.5 to 22.5 months).
      No intraoperative complications were encountered. The percentage of
      undercorrection [100% -[(treatment achieved/treatment attempted) x 100%]] [mean
      34% +/- 17% (SD), coefficient of variation (SD/mean) 0.50, range 5% to 58%] was
      higher than expected. Seven patients (47%) required enhancement due to
      undercorrection of hyperopia with diplopia (6 patients) or astigmatism with
      decreased visual acuity (1 patient). In this small series, no patient lost best
      corrected visual acuity or stereo acuity. CONCLUSION: Laser in situ
      keratomileusis can safely and effectively reduce refractive error in this group
      of patients; however, patient selection is extremely critical and enhancement was
      required in almost half the patients.

PMID- 15474826
TI  - Safety, efficacy, and stability indices of LASEK correction in moderate myopia
      and astigmatism.
AB  - PURPOSE: To evaluate the visual outcomes and complications in low to moderate
      levels of myopia and astigmatism treated with laser-assisted subepithelial
      keratectomy (LASEK) with a focus on postoperative recovery. SETTING:
      Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston,
      Massachusetts, USA. METHODS: A retrospective analysis of a case series of eyes
      treated with LASEK from 1996 to July 2002 with a follow-up of 2 years was
      performed. The LASEK technique involved creating an epithelial flap with 25 to 45
      seconds of exposure to 20% alcohol, ablating the corneal surface using 3
      different excimer lasers and nomogram adjustment, and repositioning the flap and
      applying a bandage contact lens. The main outcome measures were uncorrected
      visual acuity (UCVA), efficacy index, manifest refraction, best spectacle
      corrected visual acuity (BSCVA), safety index, retreatment rate, and
      complications. RESULTS: One hundred seventy-one eyes (85 right eyes and 86 left
      eyes) of 105 patients were studied. Preoperatively, the mean spherical equivalent
      was -2.99 diopters (D) +/- 1.43 (SD) (range -0.38 to -7.75 D) and the mean
      cylinder, -0.78 +/- 0.73 D. The UCVA ranged from 20/800 to 20/32, and the BSCVA
      ranged from 20/63 to 20/16; the median was 20/20. One week postoperatively, 96%
      of eyes had a UCVA of 20/40 or better but definitive visual recovery took more
      than 4 weeks in some eyes. Approximately 95% of eyes were within +/-1.0 D of
      emmetropia after 4 to 52 weeks; the remaining 5% did not show major deviations.
      At 4 to 52 weeks, only 1 eye was overcorrected by more than 1.0 D of manifest
      refraction. The safety index remained close to 1.0 for the follow-up after 4
      weeks. The efficacy index displayed a plateau at 0.9 from 1 month to 1 year. No
      serious complication (including recurrent erosion syndrome) was encountered. The
      mean follow-up was 31 weeks, and the retreatment rate was 2.9% up to 2 years of
      follow-up. CONCLUSIONS: The long-term safety and effectiveness of LASEK for the
      correction of low to moderate myopia and astigmatism were demonstrated. The
      treatment effect stabilized after 4 weeks.

PMID- 15474827
TI  - Analysis of the efficacy, predictability, and safety of LASEK for myopia and
      myopic astigmatism using the Technolas 217 excimer laser.
AB  - PURPOSE: To evaluate the efficacy, predictability, and safety of laser-assisted
      subepithelial keratectomy (LASEK) for the treatment of myopia and myopic
      astigmatism. SETTING: Stanford University Eye Laser Center, Stanford, California,
      USA. METHODS: This retrospective analysis comprised 102 eyes that had LASEK for
      myopia using the Bausch & Lomb Technolas 217 excimer laser. Primary outcome
      variables including uncorrected visual acuity (UCVA), best spectacle- corrected
      visual acuity (BSCVA), manifest refraction, and complications were evaluated at
      3, 6, and 12 months. Vector analysis was performed on eyes that received
      astigmatic correction. RESULTS: The mean spherical equivalent was -7.03 diopters
      (D) +/- 2.61 (SD) preoperatively, +0.19 +/- 0.64 D at 3 months, +0.23 +/- 0.82 D
      at 6 months, and +0.03 +/- 0.63 D at 12 months (P<.001). At 3, 6, and 12 months,
      the UCVA was 20/20 or better in 66%, 67%, and 83% of eyes, respectively, and
      20/40 or better in 98%, 99%, and 100%; 74%, 70%, and 83%, respectively, were
      within +/-0.5 D of emmetropia, and 89%, 86%, and 97%, respectively, were within
      +/-1.0 D. No eye lost more than 2 lines of BSCVA. At 3, 6, and 12 months, 10.0%,
      8.7%, and 0% of eyes, respectively, had trace corneal haze. Vector analysis found
      a success rate of approximately 78% to 80% in achieving the astigmatic surgical
      correction at the 3 postoperative visits. CONCLUSIONS: Laser-assisted
      subepithelial keratectomy was an effective, predictable, and safe procedure for
      the treatment of myopia and myopic astigmatism. Further studies are needed to
      determine the role of LASEK in the refractive surgery spectrum.

PMID- 15474828
TI  - Treatment of irregular astigmatism with a 213 nm solid-state, diode-pumped
      neodymium:YAG ablative laser.
AB  - PURPOSE: To present the outcome of photorefractive keratectomy (PRK) using a new
      neodymium:YAG (Nd:YAG) laser in patients with irregular astigmatism. SETTING:
      Claremont Eye Clinic, Claremont, and the University of Western Australia, Perth,
      Australia. METHODS: In 3 patients with irregular astigmatism, PRK was performed
      with a solid-state, 213 nm wavelength, 300 Hz scanning-spot, diode-pumped Nd:YAG
      ablative laser (CustomVis Pulzar laser system). The 3 patients had had previous
      PRK with penetrating keratoplasty, astigmatic keratotomy, or limbal relaxing
      incisions. At 3 and 6 months, best spectacle-corrected visual acuity (BSCVA),
      uncorrected visual acuity (UCVA), manifest refraction, contrast sensitivity, and
      corneal topography were measured. RESULTS: The first patient had a 1-line
      improvement in BSCVA and a 4-line improvement in UCVA, a 3.00 diopter (D)
      decrease in keratometric cylinder, and improvement in contrast sensitivity. The
      second patient had a 7.00 D decrease in myopia in 1 meridian and a 4.25 D
      decrease in the refractive cylinder in the other meridian. The third patient had
      a 2-line improvement in BSCVA, a 5-line improvement in UCVA, a 2.00 D decrease in
      the refractive cylinder, and improvement in contrast sensitivity. CONCLUSION: The
      laser's combination of a small spot, a fast pulse rate, and ultrafast
      tracking/scanning resulted in good results in 3 patients with difficult irregular
      astigmatism.

PMID- 15474829
TI  - PermaVision intracorneal lens for the correction of hyperopia.
AB  - PURPOSE: To evaluate the safety, predictability, and efficacy of sutureless
      synthetic keratophakia (SSK) with PermaVision intracorneal lens (Anamed)
      implantation. SETTING: Ophthalmic Hospital, Rome, Italy. METHODS: This
      retrospective study analyzed the refractive outcomes in 10 eyes of 6 patients who
      had SSK with PermaVision lens implantation for spherical hyperopia (cylinder less
      than 1.0 diopter [D]). Preoperatively, the mean spherical equivalent (SE)
      refraction was +4.33 D +/- 1.52 (SD) (range +3.00 to +6.37 D). All procedures
      were performed using the Hansatome microkeratome (Bausch & Lomb) with a superior
      hinge except in 1 eye in which the flap was cut using the Amadeus microkeratome
      (Allergan) with a nasal hinge. RESULTS: Six months after PermaVision lens
      insertion, the mean SE refraction was +0.03 +/- 0.36 D (range -0.50 to +0.38 D),
      the mean uncorrected visual acuity was 0.85 +/- 0.13 (range 0.63 to 1.00), and
      the mean best corrected visual acuity was 0.99 +/- 0.19 (range 0.63 to 1.25). No
      eye lost lines of visual acuity. In 1 eye, the lens was acutely decentered and
      had to be explanted. CONCLUSIONS: Sutureless synthetic keratophakia with the
      PermaVision intracorneal lens is a new technique for the correction of hyperopia.
      It is easy to perform as well as reversible, and the learning curve of the
      experienced laser in situ keratomileusis surgeon is short. The technique was safe
      and effective for spherical hyperopia, but longer follow-up and additional cases
      are needed to draw conclusions about the efficacy of the technique.

PMID- 15474830
TI  - Influence of intraocular lens tilt and decentration on wavefront aberrations.
AB  - PURPOSE: To investigate the influence of intraocular lens (IOL) tilt and
      decentration on higher-order aberrations (HOAs) using wavefront analysis.
      SETTING: Department of Ophthalmology, Nara Medical University, Nara, Japan.
      METHODS: Forty eyes of 40 patients with a 5.5 mm optic, foldable acrylic IOL were
      examined 4 to 48 months postoperatively. Ocular wavefront aberrations of the
      central 4.0 mm aperture diameter were measured using a Hartmann-Shack
      aberrometer. Higher-order aberrations from the 3rd to 4th order were calculated
      using Zernike polynomials. The relationship between IOL tilt and decentration,
      measured with a Scheimpflug camera, and ocular HOAs were investigated. RESULTS:
      The correlation between IOL tilt and coma-like aberrations was significant
      (r=0.431, Spearman rank correlation coefficient; P=.007). However, the
      correlation between IOL tilt and the spherical-like and total aberrations was not
      significant (P>.05), nor was the correlation between IOL decentration and coma
      like, spherical-like, and total aberrations (P>.05). CONCLUSIONS: Intraocular
      lens tilt influenced ocular coma-like aberrations. The quality of the retinal
      image may improve by reducing IOL tilt.

PMID- 15474831
TI  - Heparin in the intraocular irrigating solution in pediatric cataract surgery.
AB  - PURPOSE: To investigate the antiinflammatory effects of adding heparin sodium to
      the irrigating solution to prevent fibrinoid reaction and related long-term
      complications after pediatric cataract surgery. SETTING: Department of
      Ophthalmology, Inonu University, Turgut Ozal Medical Center, Malatya, Turkey.
      METHODS: Thirty eyes of 18 children who had cataract or other ocular surgery were
      included in the study. Bilateral cataract surgery was performed in 20 eyes of 10
      children and bilateral secondary intraocular lens (IOL) implantation in 4 eyes of
      2 children (Group 1). Four eyes of 4 children had unilateral cataract surgery and
      2 eyes of 2 children with previous perforating eye injury had synechiotomy and
      pupilloplasty (Group 2). Heparin sodium was added to the irrigating solution
      during surgery in 12 left eyes of children with bilateral surgery (Group 1a) and
      in all eyes in Group 2. Heparin sodium was not added during surgery in 12 right
      eyes of children having bilateral surgery (Group 1b, control). Early and late
      postoperative intraocular reactions were recorded and compared. RESULTS: In Group
      1a (heparin added), 6 eyes had less fibrinoid reaction and fewer related
      complications such as posterior synechias, pupil irregularity, and intraocular
      lens (IOL) decentration than the fellow right eyes. No eye in Group 1a having
      primary cataract surgery had hyphema or intraocular bleeding. Hyphema occurred on
      the first postoperative day in 1 eye in Group 1a that had secondary IOL
      implantation. CONCLUSIONS: Adding heparin sodium to the irrigating solution
      decreased postoperative inflammatory and fibrinoid reactions and related
      complications such as synechias, pupil irregularity, and IOL decentration in
      pediatric cataract surgery. However, the use of heparin during surgery can be
      risky in eyes with a defective blood-aqueous barrier such as after previous
      ocular surgery.

PMID- 15474832
TI  - Effect of intraocular lenses on preventing posterior capsule opacification:
      design versus material.
AB  - PURPOSE: To compare the preventive effect of 4 types of design- and material
      matched intraocular lenses (IOLs) on posterior capsule opacification (PCO).
      SETTING: Jinshikai Medical Foundation, Nishi Eye Hospital, Osaka, Japan. METHODS:
      After phacoemulsification, 1 of 2 matched IOLs in 3 groups was implanted in 1 eye
      and the other IOL in the contralateral eye of 4 to 6 rabbits. Three weeks
      postoperatively, posterior view and histopathological evaluations were performed
      and the capsular bending effect and amount of PCO evaluated. RESULTS: The
      capsular bending effect was similar between a sharp-edged acrylic IOL (Sensar
      40e, AMO) and a sharp-edged silicone IOL (ClariFlex, AMO) and between the Sensar
      40e IOL and a sharp-edged acrylic IOL (AcrySof, Alcon Laboratories). There was no
      significant difference between IOL types in the amount of PCO. The capsular bend
      effect was slightly better and the PCO amount slightly less with the ClariFlex
      IOL than with the round-edged silicone PhacoFlex II IOL (AMO). CONCLUSIONS: There
      was no substantial difference in PCO prevention between IOLs with sharp posterior
      optic edges, regardless of the IOL's material composition. The anterior edge
      design appeared to have no preventive effect. These results confirm that a sharp
      posterior optic edge is the main factor in preventing PCO.

PMID- 15474833
TI  - Comparative penetration of moxifloxacin and gatifloxacin in rabbit aqueous humor
      after topical dosing.
AB  - PURPOSE: To evaluate the aqueous penetration of the fourth-generation
      fluoroquinolones moxifloxacin and gatifloxacin. SETTING: University of Arizona,
      Tucson, Arizona, USA. METHODS: Forty eyes of 20 New Zealand white rabbits were
      divided into 2 experimental groups. In Experiment I rabbits (20 eyes), a
      commercial preparation of topical gatifloxacin 0.3% was administered to 9 eyes
      and moxifloxacin 0.5% to 9 eyes; 2 eyes served as a control. Eyes were dosed
      according to a keratitis protocol; ie, every 15 minutes for 4 hours. The aqueous
      humor was sampled 10 minutes after the last dose. Experiment II rabbits (20 eyes)
      were dosed according to a cataract prophylaxis protocol; ie, 4 times a day for 10
      days. The aqueous humor was sampled 1 hour after the last dose of antibiotic in
      12 eyes and 24 hours after the last dose in 8 eyes. High-performance liquid
      chromatography was used to determine the fluoroquinolone concentration. RESULTS:
      In the keratitis dosing protocol, the mean concentration of moxifloxacin in the
      aqueous (n=9) was 11.057 microg/mL (range 7.66 to 18.87 microg/mL), which was
      significantly higher than the mean concentration of gatifloxacin (n=8) (7.570
      microg/mL [range 4.75 to 10.86 microg/mL]) (P=.030). In the cataract prophylaxis
      dosing protocol, the mean aqueous concentration of moxifloxacin (n=6) was 1.745
      microg/mL (range 0.92 to 3.87 mg/mL). The mean concentration of gatifloxacin
      (n=6) was 1.207 microg/mL (range 0.44 to 2.44 microg/mL). The difference was not
      statistically significant (P=.359). CONCLUSIONS: Higher mean levels (x1.46) of
      aqueous penetration were achieved with moxifloxacin than with gatifloxacin in the
      keratitis-dosing model. There was no statistically significant difference between
      the 2 drugs in the cataract prophylaxis dosing model. Both antibiotics had
      aqueous levels in excess of the minimum inhibitory concentration for most
      pathogenic organisms in both models.

PMID- 15474834
TI  - Capsulorhexis ovaling and capsular bag stretch after rigid and foldable
      intraocular lens implantation: experimental study in pediatric human eyes.
AB  - PURPOSE: To compare the amount of capsulorhexis ovaling and capsular bag stretch
      produced by various intraocular lenses (IOLs) implanted in pediatric human eyes
      obtained post-mortem. SETTING: David J. Apple, MD Laboratories for Ophthalmic
      Devices Research, John A. Moran Eye Center, Salt Lake City, Utah, USA. METHODS:
      In this nonrandomized comparative study, 16 pediatric human eyes obtained
      postmortem were divided into 2 groups: Eight eyes were obtained from children
      younger than 2 years (Group A), and 8 eyes were obtained from children older than
      2 years (Group B). All eyes were prepared according to the Miyake-Apple posterior
      video technique. Six types of rigid and foldable posterior chamber IOLs
      manufactured from poly(methyl methacrylate) (single-piece), silicone (plate and
      loop haptics), and hydrophobic acrylic (single-piece and 3-piece AcrySof, Alcon
      Laboratories) biomaterials were implanted. The capsulorhexis opening and capsular
      bag diameters were measured before IOL implantation and after in-the-bag IOL
      fixation with the haptics (or the main axis) at the 3 to 9 o'clock meridian. The
      percentage of ovaling of the capsulorhexis opening was calculated by noting the
      difference in the opening's horizontal diameter before and after IOL
      implantation. The percentage of capsular bag stretch was also calculated by
      noting the difference in the horizontal capsular bag diameter before and after
      IOL implantation. RESULTS: All IOLs produced ovaling of the capsulorhexis opening
      and stretching of the capsular bag parallel to the IOL haptics. There were
      significant differences in capsulorhexis ovaling and capsular bag stretch
      (P<.001, analysis of variance) between the 6 IOL types in each group of eyes. The
      postimplantation difference was significant only between the single-piece
      hydrophobic acrylic IOL (AcrySof) and the other IOLs. The single-piece
      hydrophobic acrylic IOL was associated with significantly less capsulorhexis
      ovaling and capsular bag stretch in both groups (mean 12.06% +/- 0.59% [SD] and
      7.6% +/- 1.47%, respectively). CONCLUSIONS: Modern rigid and foldable IOLs
      designed for the adult population implanted in the capsular bag of infants and
      children produced variable degrees of capsulorhexis ovaling and capsular bag
      stretch. The Miyake-Apple posterior video technique confirmed the well-maintained
      configuration of the capsular bag (with minimal ovaling) after implantation of a
      single-piece hydrophobic acrylic IOL because of its flexible haptic design.

PMID- 15474835
TI  - Expression of laminin-5 with amniotic membrane transplantation in excimer laser
      ablated rat corneas.
AB  - PURPOSE: To investigate the expression of laminin-5 during epithelial healing and
      evaluate its expression in vivo using rat corneas on which amniotic membrane was
      applied to cover the wound after excimer laser photoablation. SETTING: Department
      of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea. METHODS:
      Myopic photorefractive keratectomy (PRK) with a 100 microm deep ablation was
      performed in Sprague Dawley rats killed 6, 12, 24, 48, 72, and 96 hours after the
      procedure. In the first group of 30 rats, the excimer laser-ablated cornea was
      covered with amniotic membrane after PRK. Thirty other rats in which no amniotic
      membrane treatment was used served as controls. Immunohistochemical and
      immunofluoresce in techniques were used to monitor the expression of laminin-5,
      gamma2, and gamma1 in the rat corneas. Immunoblotting was used to compare the
      expression of laminin between the amniotic membrane group and the control group.
      RESULTS: In the immunoblotting study, laminin-5, alpha3, and gamma2 increased 24
      hours after amniotic membrane treatment compared to the control group. At 12
      hours, in vivo immunostaining of the corneas in both groups expressed laminin,
      but laminin-5 and gamma2 were more intensely expressed in the amniotic membrane
      group. This continued until reepithelialization. Expression of the gamma1 chain
      was not different between the 2 groups. CONCLUSION: With the use of amniotic
      membrane, the expression of laminin-5 and gamma2 was faster and more intense than
      in a control group during reepithelialization of excimer laser-ablated rat
      corneas.

PMID- 15474836
TI  - Effect of exogenous keratinocyte growth factor on corneal epithelial migration
      after photorefractive keratectomy.
AB  - PURPOSE: To investigate the effect of topical keratinocyte growth factor (KGF) on
      wound healing after photorefractive keratectomy (PRK) and laser in situ
      keratomileusis (LASIK). SETTING: Department of Ophthalmology, Rayne Institute,
      St. Thomas' Hospital, London, United Kingdom, St. Erick's Eye Hospital,
      Stockholm, Sweden, and the University of Regensberg, Regensberg, Germany.
      METHODS: In a placebo-controlled trial, 24 New Zealand white female rabbits were
      divided into 3 equal groups. Group 1 (n=8) had myopic PRK (6.0 diopters [D])
      using the Technolas 217z laser (Bausch & Lomb). Group 2 and Group 3 had myopic
      LASIK (6.0 D) with a flap depth of 140 microm and 180 microm, respectively.
      Topical KGF (20 microg/mL) was administered to half the treated eyes in each
      group intraoperatively and postoperatively; the other half received placebo
      eyedrops. Epithelial closure, corneal haze, and keratocyte activation in the
      rabbit eyes were analyzed and compared with those in placebo-controlled eyes for
      5 weeks postoperatively. RESULTS: In Group 1, the mean reepithelialization after
      PRK was 0.10 mm2/h +/- 0.02 (SD) in the KGF group and 0.33 +/- 0.05 mm2/h in the
      control group (P=.001). There was no significant difference in the mean
      backscatter between the KGF eyes (154 +/- 45.95) and the control eyes (141 +/-
      38.45) after PRK (P=.42). Histology revealed reduced epithelial cell layers in
      the KGF group and comparable keratocyte density as in the control group. In
      Groups 2 and 3, there was no significant difference in backscatter, epithelial
      layers, and keratocyte density between KGF and control eyes after LASIK.
      CONCLUSIONS: Topical KGF (20 microg/mL) delayed reepithelialization after PRK. It
      had no effect on stromal wound healing in LASIK eyes with an intact epithelial
      barrier.

PMID- 15474837
TI  - Beyond the P: II: precluding a puddle of P values.
AB  - This is the second in a 4-part series discussing the proper use, interpretation,
      and limitations of P values.

PMID- 15474838
TI  - Complications of foldable intraocular lenses requiring explantation or secondary
      intervention--2003 survey update.
AB  - The sixth annual survey of complications associated with foldable intraocular
      lenses (IOLs) requiring explantation or secondary intervention was sent to
      members of the American Society of Cataract and Refractive Surgery and the
      European Society of Cataract and Refractive Surgeons. Preoperative data about
      visual acuity, patient signs and symptoms, and complications requiring IOL
      removal were evaluated. Complications were then tabulated for each of the
      following major foldable IOL groups: 3-piece monofocal silicone, 3-piece
      hydrophobic acrylic, 1-piece hydrophobic acrylic with haptics, 3-piece
      hydrophilic acrylic (hydrogel), 1-piece hydrophilic acrylic (hydrogel), 1-piece
      plate-type silicone, 3-piece multifocal silicone, and Collamer. Two hundred
      seventy-three surveys were returned for evaluation. Dislocation/decentration,
      incorrect lens power, IOL calcification, and glare/optical aberrations were the
      most common reasons for removing foldable IOLs. Good surgical technique, accurate
      IOL power measurements, and high manufacturing standards for foldable IOL
      materials and designs are the most important factors in avoiding complications
      with foldable IOLs.

PMID- 15474839
TI  - Secondary pigmentary glaucoma associated with piggyback intraocular lens
      implantation.
AB  - A 51 year-old man developed bilateral pigmentary glaucoma with uncontrolled
      intraocular pressure (IOP) and signs of pigmentary dispersion syndrome after
      piggyback intraocular lens (IOL) implantation. Cataract surgery had been
      performed with in-the-bag implantation of poly(methyl methacrylate) IOLs in both
      eyes. Increasing myopia was subsequently corrected with implantation of an
      AcrySofIOL (Alcon Laboratories) in the ciliary sulcus of each eye. After the
      second implantation, the IOP was unresponsive to antiglaucoma medications, the
      visual field was damaged, and the visual acuity decreased. Ultrasound
      biomicroscopy showed that the haptics and the sharp edge of the IOL were chafing
      the posterior surface of the iris. After the IOL in the sulcus was removed, the
      IOP was stabilized by medications. This case highlights the importance of the IOL
      choice for sulcus implantation to avoid the complications of pigmentary
      dispersion syndrome.

PMID- 15474840
TI  - Traumatic expulsive iridodialysis after small-incision sutureless cataract
      surgery.
AB  - Phacoemulsification with intraocular lens (IOL) implantation was performed in the
      right eye of an 84-year-old woman using a small clear corneal incision. Ten weeks
      after surgery, the patient fell, which caused traumatic iridodialysis and hyphema
      with expulsion of the iris through the surgical corneal incision. Apart from a
      transient rise in intraocular pressure, no other complication was identified and
      the visual acuity returned to 20/20 within 2 months. The IOL remained in situ and
      undisturbed in the capsular bag, and the retina remained flat, suggesting that an
      IOL in the capsular bag may provide a stable barrier to prevent tissue loss from
      the posterior segment.

PMID- 15474841
TI  - Early opacification of SI-40NB silicone intraocular lenses.
AB  - We report 4 cases of silicone intraocular lens (IOL) opacification (SI-40NB,
      Allergan Inc.) in patients who had phacoemulsification between April and June
      2003. The opacification was observed on the first postoperative day in all cases.
      The appearance of the silicone IOLs ranged from milky gray to a yellow hue and
      affected the entire optical component homogeneously. The patients did not
      complain about their vision, and visual acuity was only slightly affected; 3 of
      the 4 patients had a best corrected visual acuity of 20/30, and no anterior
      chamber reaction was observed. Contrast sensitivity was reduced in all cases.
      Careful scrutiny of medical histories failed to reveal factors that might have
      predisposed the patients to IOL opacification.

PMID- 15474842
TI  - Anterior capsule opacification spanning the anterior surface of an AcrySof
      intraocular lens.
AB  - We present a case of linear anterior capsule opacification bridging the anterior
      surface of an AcrySof intraocular lens (IOL) (Alcon Laboratories). A 75-year-old
      woman had uneventful cataract extraction and in-the-bag IOL insertion. Before
      implantation, the IOL was folded with a holding and an implantation forceps. The
      formation of a capsule bridge was observed on routine examination 20 days
      postoperatively. The bridge spanned the IOL parallel to the fold along the
      central axis, where the forceps had grasped the IOL. The bridge did not grow or
      regress for 24 months after surgery. The formation of the bridge along the fold
      might have been facilitated by a minute, undetected structural change in the
      AcrySof IOL created during folding.

PMID- 15474843
TI  - Idiopathic opacification of Berger's space.
AB  - We report a case of idiopathic opacification of Berger's space in a 68-year-old
      man. The opacification was in the retrolental space between the crystalline lens
      and the anterior vitreous in the right eye. Opaque fluid was surgically removed,
      and chemical analysis detected a high concentration of protein and a low
      concentration of mucopolysaccharides. No underlying pathology was observed.

PMID- 15474844
TI  - Interrupted sutures at the hinge site to manage a free flap during laser in situ
      keratomileusis.
AB  - Two patients developed free flaps intraoperatively during laser in situ
      keratomileusis. After excimer laser treatment was performed, the free flap was
      replaced, maintaining proper alignment. Interrupted sutures were placed
      superiorly at the intended hinge site to secure the free flap. The uncorrected
      visual acuity was 20/30 in the affected eyes of both patients after treatment. At
      the 6-month follow-up, there were no flap-related complications and there was no
      loss of best corrected visual acuity.

PMID- 15474845
TI  - Preoperative and intracameral antibiotic prophylaxis and intraocular
      contamination during cataract surgery.

PMID- 15474847
TI  - Comparison of anterior capsule electron microscopy findings with and without
      trypan blue stain.

PMID- 15474846
TI  - Iris-fixated phakic IOLs to correct postoperative anisometropia in unilateral
      cataract patients with bilateral high myopia.

PMID- 15474848
TI  - Posterior capsule opacification with Hydroview H60M foldable intraocular lenses.

PMID- 15474849
TI  - The relationship between pain and negative affect in older adults: anxiety as a
      predictor of pain.
AB  - Although the relationship between pain and negative affect (e.g., depression,
      anxiety, and anger) has been repeatedly demonstrated in younger populations, the
      findings have varied widely among studies. Additionally, there has been minimal
      research on the relationship between negative affect and acute pain in older
      adults. This is especially disturbing when one considers that the population is
      at a higher risk for painful conditions than any other age group. The current
      study investigated the relative contributions of state anxiety, trait anxiety,
      depression, state anger, and trait anger to acute pain in an elderly,
      postsurgical population. The participants (n = 100) were all over the age of 65
      and were receiving treatment on an inpatient rehabilitation unit following
      orthopedic surgery (e.g., knee or hip replacement surgery). Data were analyzed by
      means of multiple regression, regressing the five predictor variables on the
      single criterion variable. Results indicated that the only significant predictor
      of pain in this population was state anxiety, and that this variable alone
      accounted for 27% of the variance in pain. Treatment implications and suggestions
      for further research were discussed.

PMID- 15474850
TI  - Unresolved grief in combat veterans with PTSD.
AB  - Clinicians have documented the importance of loss of comrades during combat as a
      significant source of distress. However, empirical studies have not focused on
      unresolved grief as a possible outcome of combat experiences. Consequently,
      unresolved grief has often been treated "after the fact" in the context of
      treating PTSD and depressive symptoms. In this study, we therefore, sought to
      demonstrate the prominence of combat-related grief-specific symptoms in a sample
      of Vietnam veterans being treated for PTSD. Our results indicated that indeed
      this sample of veterans reported high levels of grief-specific symptoms
      comparable to that found in bereaved individuals whose spouse had recently died,
      verifying its prominence as an important component of combat-related stress.
      Furthermore, grief severity was uniquely associated with losses of comrades
      during combat whereas no such relationship was shown for trauma or depressive
      symptoms. The latter finding suggested that in fact higher levels of grief
      stemmed from interpersonal losses during the war and was not simply an artifact
      of current general distress level.

PMID- 15474851
TI  - Music performance anxiety and occupational stress amongst opera chorus artists
      and their relationship with state and trait anxiety and perfectionism.
AB  - This study explored the inter-relationships among state and trait anxiety,
      occupational stress, perfectionism, aspiration, and music performance anxiety in
      a group of elite operatic chorus artists employed full-time by a national opera
      company. The chorus artists reported higher trait anxiety, higher occupational
      role concerns, and higher occupational personal strain than normative samples.
      Higher scores on personal resources were associated with the higher scores on
      trait anxiety. It appears that these resources were used adaptively to manage
      anxiety. High trait anxiety was also associated with high personal strain in the
      work environment. Anxiety was not related to occupational roles or issues related
      to the physical environment or working conditions. These results suggest that
      while trait anxiety and music performance anxiety were closely associated,
      occupational stress makes a separate contribution to the quality of working life
      experienced by elite choral artists.

PMID- 15474852
TI  - Interpersonal appraisals of emotionally distressed persons by anxious and
      dysphoric individuals.
AB  - Coyne [J. Abnorm. Psychol. 85 (1976a) 186; Psychiatry 29 (1976b) 28] first
      reported that depressed persons were negatively appraised interpersonally by
      interaction partners. The purpose of the current study was to replicate previous
      findings extending Coyne's theory to anxious individuals and to assess how
      anxiety and depression of the raters may affect these ratings. Anxious,
      dysphoric, and control participants watched a video of an actor portraying
      anxious, depressed, or neutral affect (n = 208). Results indicated that the actor
      portraying depressed affect was assessed more negatively than the actor
      portraying anxious affect who, in turn, was assessed more negatively than the
      actor portraying neutral affect. However, anxious and dysphoric participants did
      not differ from control participants in their ratings of the videos.

PMID- 15474853
TI  - Agoraphobic behavior and panic attack: a study of male twins.
AB  - We used data from 3372 pairs of male twins from the Vietnam Era Twin Registry to
      examine comorbidity and familial influences on the frequently observed
      association between agoraphobic behavior and panic. Due to low prevalence of DSM
      III-R-defined panic disorder, we also examined subjects who had experienced at
      least one panic attack during their lives. Agoraphobic behavior among individuals
      with a history of panic attacks showed familial aggregation (odds ratio = 5.7; P
      = .018 ). Probands with panic attacks and agoraphobic behavior and their co-twins
      had higher risk of major depression than probands without agoraphobic avoidance
      and their co-twins (P = .01). Groups did not differ for alcohol dependence or
      antisocial personality. Agoraphobic behavior associated with panic attack is
      familial and associated with comorbid major depression. Agoraphobia following
      panic attack does not seem to reflect severity as agoraphobic behavior in the
      proband was unrelated to risk of panic attacks in the co-twin.

PMID- 15474854
TI  - Effect of stimulus type and worry on physiological response to fear.
AB  - The current study investigated whether the immediacy and concreteness of fear
      stimuli play an important role in the effects of trait worry on physiological
      response to fear. One hundred and eight participants were exposed to one of three
      fear-provoking stimuli: an actual spider (immediate and concrete), an opaque box
      which they were told contained a spider (immediate but abstract), or a recorded
      script (distant and abstract). Participants were yoked by levels of worry and
      gender. Heart rate, vagal tone, and skin conductance were recorded. The
      combination of high worry and an actual spider caused the largest decrease in
      vagal tone, but both the actual spider and opaque box increased skin conductance
      regardless of worry level. The results suggest that factors, such as the type of
      fear stimulus and the type of physiological measures used, are vital in
      understanding the reasons for and the limits of fear activation.

PMID- 15474855
TI  - Psychometric properties of disability measures among patients with social anxiety
      disorder.
AB  - BACKGROUND: Although recognition of the importance of disability as a construct
      has increased in recent years, there has been little examination of the
      reliability and validity of disability measures. METHODS: This study examined
      three disability measures, the Liebowitz Self-Rated Disability Scale (LSRDS), the
      clinician-rated Disability Profile (DP), and the Sheehan Disability Scale (SDS)
      among patients with a primary diagnosis of social anxiety disorder. RESULTS: The
      disability measures correlated strongly with each other, as well as with measures
      of social anxiety, depressive symptoms, and patients' subjectively-evaluated
      quality of life. The LSRDS and DP were more internally consistent than the SDS
      Total Score. All measures discriminated between patients with generalized and non
      generalized social anxiety disorder. However, the LSRDS and DP also showed
      greater sensitivity to ecological indicators of distress than the SDS. Social
      anxiety symptoms accounted for significant variance in disability, above and
      beyond that accounted for by depressive symptoms. CONCLUSIONS: Overall, the
      LSRDS, DP, and SDS appear to be valid tools in the study of disability in social
      anxiety disorder, although the LSRDS and the DP appear to be somewhat more
      sensitive to the experiences of socially anxious patients.

PMID- 15474856
TI  - Late-life anxiety disorders among Puerto Rican primary care patients: impact on
      well-being, functioning, and service utilization.
AB  - With the growing population of older Hispanic adults there is a need for
      additional research on the mental health care of this patient group. This study
      explored the impact of anxiety disorders on the health status of 291 older (>/=50
      years) Puerto Rican primary care patients (n = 65 with anxiety disorders, n = 226
      without anxiety disorders). All analyses controlled for potential confounding
      variables, including depression diagnosis and physical health burden. Logistic
      regression indicated that anxiety disorders were associated with higher
      psychological distress, suicidality, and emergency room service utilization, as
      well as lower instrumental functioning and perceived health quality. Analysis of
      covariance indicated that both anxiety disorder status and history of ataque de
      nervios were related to higher percentages of lifetime somatic symptoms. These
      data highlight the need for improved recognition and treatment of anxiety
      disorders in older Puerto Rican adults.

PMID- 15474858
TI  - Anti-IgE therapy.
AB  - IgE has a central role in the initiation of allergic hypersensitivity reactions.
      Pioneered by the development of humanized monoclonal antibodies directed against
      IgE, anti-IgE therapy represents an original approach to the treatment of
      allergic disease and has demonstrated promise in preventing the symptoms of
      asthma, allergic rhinitis, and food allergy. The primary mechanism of action of
      anti-IgE therapy is the reduction in serum levels of IgE and FcepsilonRI
      expression on mast cells and basophils.

PMID- 15474859
TI  - New approaches in immunotherapy: allergen vaccination with immunostimulatory DNA.
AB  - Despite its success, conventional immunotherapy is saddled with a number of
      encumbrances. An allergenic vaccine that could reduce allergenicity, maintain
      immunogenicity, and be given in a few doses would have important therapeutic
      implications, as millions of patients with poorly controlled allergic rhinitis
      and asthma would be candidates for such a form of immunomodulation. This article
      addresses a specific adjuvant approach to immunotherapy in which highly active
      immunostimulatory phosphorothioate oligodeoxyribonucleotide moieties are linked
      to the principal allergenic moiety of a relevant aeroallergen.

PMID- 15474860
TI  - Role of tumor necrosis factor alpha in asthma.
AB  - Asthma is a heterogeneous disease in which various cytokines orchestrate airway
      inflammation. Tumor necrosis alpha (TNF-alpha) is a proinflammatory cytokine that
      has been implicated in the modulation of inflammation in various diseases,
      including asthma. Although TNF-alpha blocking strategies have been an effective
      therapeutic modality in diseases such as rheumatoid arthritis, their role in
      asthma and the effects of the blockade in asthma is poorly understood. This
      article examines the role of TNF-alpha in asthma and the effects of blocking TNF
      alpha as a possible therapeutic option in patients with severe corticosteroid
      dependent asthma.

PMID- 15474861
TI  - Anti-interleukin-4 therapy.
AB  - Interleukin 4 (IL-4) mediates important pro-inflammatory functions in asthma,
      including T helper cell type 2 lymphocyte differentiation, induction of IgE
      production, up-regulation of IgE receptors, expression of vascular cell-adhesion
      molecule 1, promotion of eosinophil transmigration into the lungs, inhibition of
      T-lymphocyte apoptosis, and mucus hypersecretion. The role of IL-4 in the
      pathogenesis of asthma is supported by identification of polymorphisms linked to
      asthma in the IL-4 gene promoter and proteins involved in IL-4 signaling. Several
      approaches to IL-4 antagonism are or have been in clinical development. This
      article examines IL-4 and the antagonists that have been developed. Early trial
      results and the future of anti-IL-4 therapy are discussed.

PMID- 15474862
TI  - Adhesion molecules as therapeutic targets.
AB  - This article focuses on the importance of cell-adhesion molecules in the process
      of allergic inflammation. After reviewing the contribution of different families
      of adhesion molecules to the cellular recruitment cascade, phenotypic
      characteristics of leukocyte subtypes are discussed to illustrate how expression
      of differing patterns of adhesion molecules and their counterligands within
      tissues influence the type of inflammatory response that occurs. The involvement
      of adhesion molecules in allergic inflammation in animal models and human studies
      is described. Examples of specific adhesion-molecule antagonists are provided,
      and results of their use in human studies of allergic and other inflammatory
      conditions are discussed.

PMID- 15474863
TI  - Topical treatment of atopic dermatitis.
AB  - Topical therapy of atopic dermatitis should incorporate an understanding of the
      underlying immune abnormalities of this complex chronic skin disease. Avoidance
      of irritants and proven allergens, skin hydration, and use of emollients and anti
      inflammatory therapy help maintain a normal skin barrier. Topical calcineurin
      inhibitors have been added to the topical treatment armamentarium. Although the
      optimal treatment approach remains to be defined, several studies suggest the use
      of topical calcineurin inhibitors as early intervention therapy and topical
      corticosteroids as rescue therapy.

PMID- 15474864
TI  - Anti-interleukin-5 therapy for asthma and hypereosinophilic syndrome.
AB  - Interleukin 5 (IL-5) is a key cytokine in the regulation of eosinophilia and
      eosinophil activation in humans. Monoclonal antibodies to anti-IL-5 have become
      available for use in clinical studies in humans. This article discusses the
      rationale for the use of anti-IL-5 therapy in asthma and hypereosinophilic
      syndrome and summarizes the available clinical data on the use of anti-IL-5 to
      treat these disorders.

PMID- 15474865
TI  - Chemokine receptors: understanding their role in asthmatic disease.
AB  - The incidence, prevalence, and severity of asthma have been increasing steadily
      in recent years. Prophylactic treatment of this disease and of episodic asthmatic
      flares is aimed at preventing excessive inflammation in lung tissue and airways.
      Because chemokines and chemokine receptors are critical mediators of leukocyte
      trafficking and recruitment, there is the potential to pharmaceutically target
      these proteins to regulate inflammation. Asthma-associated inflammation is
      characterized by the infiltration of eosinophils and T helper type 2 cells. Early
      studies investigated the role of chemokine receptors, which have been shown to
      predominate on these cell populations.

PMID- 15474866
TI  - Sublingual and oral immunotherapy.
AB  - Sublingual immunotherapy (SLIT) is a viable alternative to the subcutaneous route
      for the treatment of respiratory allergy, whereas the pure oral route has been
      abandoned because of its lack of efficacy. The main distinctive feature of SLIT
      is its optimal safety profile, which has been demonstrated in adults and
      children. The indications for SLIT are similar to those for the subcutaneous
      route. A long-lasting effect has been demonstrated for the sublingual route, but
      data are needed to determine the optimal dose and the preventive effect in
      asthma.

PMID- 15474867
TI  - Food allergy therapy.
AB  - Novel approaches to the treatment and prevention of IgE-mediated food allergy
      include anti-IgE, food allergy vaccines, herbal preparations, and probiotics.
      They bring real hope to the patients for whom no specific therapy is available.
      These immunomodulatory therapies have to be evaluated carefully for potential
      side effects, such as overstimulation of T helper cell type 1 immune antibodies.
      Animal models of food allergy are invaluable in testing new therapies for food
      allergy.

PMID- 15474868
TI  - Genetically modified allergens.
AB  - For more than 90 years, allergen-specific immunotherapy, the only causative
      allergy treatment, has remained basically unchanged. The development of molecular
      biology techniques has led to the preparation of individual recombinant allergens
      from the most important allergen sources. Recombinant allergens can be used to
      determine the individual sensitization profile of allergic patients and have
      allowed the development of novel therapeutic tools. This article summarizes data
      on genetically modified recombinant allergen derivatives with reduced allergenic
      activity, which may be used to improve the safety and efficacy of specific
      immunotherapy.

PMID- 15474869
TI  - Probiotics and down-regulation of the allergic response.
AB  - The first clinical trials with probiotics, especially in the treatment of atopic
      eczema, have yielded encouraging results. Experimental studies have found that
      probiotics exert strain-specific effects in the intestinal lumen and on
      epithelial cells and immune cells with anti-allergic potential. These effects
      include enhancement in antigen degradation and gut barrier function and induction
      of regulatory and proinflammatory immune responses, the latter of which occurs
      more likely beyond the intestinal epithelium. Future studies should address more
      accurately how these and other possible mechanisms operate in the complex
      gastrointestinal macroenvironment in vivo and how these mechanisms are related to
      the clinical effects in a dose-dependent manner.

PMID- 15474870
TI  - Does enteral nutrition compared to parenteral nutrition result in better outcomes
      in critically ill adult patients? A systematic review of the literature.
AB  - OBJECTIVE: Nutritional support is part of the standard of care for the critically
      ill adult patient. In the average patient in the intensive care unit who has no
      contraindications to enteral nutrition (EN) or parenteral nutrition (PN), the
      choice of route for nutritional support may be influenced by several factors.
      Because EN and PN are associated with risks and benefits, we systematically
      reviewed and critically appraised the literature to compare EN with PN the
      critically ill patient. METHODS: We searched computerized bibliographic
      databases, personal files, and relevant reference lists to identify potentially
      eligible studies. Only randomized clinical trials that compared EN with PN in
      critically ill patients with respect to clinically important outcomes were
      included in this review. In an independent fashion, relevant data on the
      methodology and outcomes of primary studies were abstracted in duplicate. The
      studies were subsequently aggregated statistically. RESULTS: There were 13
      studies that met the inclusion criteria and, hence, were included in our meta
      analysis. The use of EN as opposed to PN was associated with a significant
      decrease in infectious complications (relative risk = 0.64, 95% confidence
      interval = 0.47 to 0.87, P = 0.004) but not with any difference in mortality rate
      (relative risk = 1.08, 95% confidence interval = 0.70 to 1.65, P = 0.7). There
      was no difference in the number of days on a ventilator or length of stay in the
      hospital between groups receiving EN or PN (Standardized Mean Difference [SMD] =
      0.07, 95% confidence interval = -0.2 to 0.33, P = 0.6). PN was associated with a
      higher incidence of hyperglycemia. Data that compared days on a ventilator and
      the development of diarrhea in patients who received EN versus PN were
      inconclusive. In the EN and PN groups, complications with enteral and parenteral
      access were seen. Four studies documented cost savings with EN as opposed to PN.
      CONCLUSION: The use of EN as opposed to PN results in an important decrease in
      the incidence of infectious complications in the critically ill and may be less
      costly. EN should be the first choice for nutritional support in the critically
      ill.

PMID- 15474871
TI  - Changes in multiple health outcomes at 12 and 24 weeks resulting from 12 weeks of
      exercise counseling with or without dietary counseling in obese adults.
AB  - OBJECTIVE: We compared health outcomes in obese adults who underwent 12 wk of
      exercise counseling with or without dietary counseling, followed by 12 wk of
      observational monitoring. METHODS: Ninety adults (77 women and 13 men; 42.6 +/-
      6.0 y; body mass index, 31.5 +/- 2.8 kg/m(2)) were randomly assigned to exercise
      only (EX) or diet-plus-exercise (DEX) groups and counseled weekly by exercise
      physiologists on a 12-wk walking program. DEX subjects were also counseled by
      dietitians on a hypocaloric diet (-500 kcal/d). From weeks 12 to 24, subjects
      were monitored but not counseled. At weeks 0, 12, and 24, data collection
      included body composition (air displacement plethysmography), fitness (maximum
      oxygen consumption, 3-min step-test, and timed mile), plasma lipids, weight loss
      efficacy (Weight Efficacy Life-Style Questionnaire), quality of life (Medical
      Outcomes Study Health Survey-Short Form 36), and mood (Profile of Mood States).
      RESULTS: At 12 and 24 wk, weight and body mass index decreased in DEX subjects
      (both P < 0.05) but not in EX subjects. However, lean body mass increased
      significantly in EX (24 wk, P < 0.05) but not in DEX subjects. In both groups,
      fat mass decreased (P < 0.05 for EX subjects at 24 wk; P < 0.05 for DEX subjects
      at 12 and 24 wk) and waist circumference decreased (P < 0.05 for EX subjects at
      12 and 24 wk; P < 0.05 for DEX subjects at 12 and 24 wk). At 12 and 24 wk, DEX
      subjects showed decreased levels of total plasma cholesterol and triacylglycerols
      (both P < 0.05) and improvements with regard to the Weight Efficacy Life-Style
      Questionnaire (P < 0.05), three domains of the Medical Outcomes Study Health
      Survey-Short Form 36 (all P < 0.05), and three domains of the Profile of Mood
      States (all P < 0.05) that were not seen in EX subjects. CONCLUSIONS: Exercise
      counseling for 12 wk in obese adults improves some body composition indices that
      can be sustained over 12 wk of monitoring. The addition of dietary counseling
      increases improvements in body composition, lipid profiles, and several
      psychological parameters.

PMID- 15474872
TI  - Waist circumference and waist-to-hip ratio as predictors of serum concentration
      of lipids in Brazilian men.
AB  - OBJECTIVE: It is unknown whether waist circumference can predict a lipid profile
      beyond that predicted by body fatness alone, after adjustment for important
      confounding variables such as smoking, alcohol intake, and physical activity. The
      purpose of this non-clinical, healthy-subject study was to test this hypothesis.
      METHODS: Data refer to 416 men, ages 20 to 58 y with a body mass index between
      18.5 and 29.9 kg/m(2), who were blood donors living in a Brazilian city. Alcohol
      consumption, smoking, and physical activity were evaluated by interview; body fat
      was measured by electrical bioimpedance, and weight, height, and waist and hip
      circumferences were measured by trained anthropometrists. Multiple linear
      regression analysis was performed to quantify the association between
      measurements of fat distribution (waist circumference and waist-to-hip ratio) and
      the ratio of total cholesterol to high-density lipoprotein cholesterol and
      triacylglycerols independently of measurements of fatness and potentially
      confounding factors. RESULTS: Waist circumference was strongly correlated with
      percentage of body fat (r = 0.90), whereas waist-to-hip ratio was less correlated
      (r = 0.55). After adjustment for age, percentage of body fat, smoking, alcohol
      intake, and physical activity, waist circumference was not significantly related
      to the ratio of total cholesterol high-density lipoprotein cholesterol, whereas
      the waist-to-hip ratio was strongly associated among the youngest subjects (beta
      = 3.51, P = 0.005). CONCLUSION: Although several studies have analyzed the
      association between serum lipids with anthropometric markers, few, including the
      present one, support waist circumference as a good predictor of lipid profile.

PMID- 15474873
TI  - Effects of a long-term vegetarian diet on biomarkers of antioxidant status and
      cardiovascular disease risk.
AB  - OBJECTIVE: We compared plasma biomarkers of antioxidant status, oxidative stress,
      inflammation, and risk for coronary heart disease in long-term vegetarians and
      age- and sex-matched omnivores. METHODS: Thirty vegetarians (mean age +/-
      standard deviation: 44.2 +/- 9.0 y) were recruited. The subjects had been
      vegetarian for 5 to 55 y (21.8 +/- 12.2 y). The control group comprised 30 adults
      selected by age-stratified sampling from a community health project (mean age:
      44.0 +/- 9.2 y). Fasting plasma total antioxidant status (ferric-reducing
      antioxidant power), ascorbic acid (AA), alpha-tocopherol (total and lipid
      standardized), malondialdehyde, total cholesterol, triacylglycerol, uric acid
      (UA), and high-sensitivity C-reactive protein (hsCRP) were measured. RESULTS:
      Plasma AA was significantly higher in the vegetarians than in the omnivores (90.5
      +/- 21.0 and 61.8 +/- 17.0 microM; P < 0.001). The vegetarians had lower
      concentrations of triacylglycerol, UA, and hsCRP. Plasma total and lipid
      standardized alpha-tocopherol concentrations were also lower in the vegetarians:
      22.0 +/- 5.9 and 27.0 +/- 7.9 microM versus 3.76 +/- 0.57 and 4.23 +/- 0.58
      microM per millimoles per liter of total cholesterol plus triacylglycerol,
      respectively. There was a significant inverse correlation between AA and UA (r = 
      0.343, P < 0.01; n = 60) and between AA and hsCRP (r = -0.306, P < 0.05; n = 55).
      Plasma ferric-reducing antioxidant power and malondialdehyde did not differ
      significantly between groups; however, the contribution of AA to the total
      antioxidant capacity of plasma was approximately 50% greater in the vegetarians.
      CONCLUSIONS: A long-term vegetarian diet is associated with markedly higher
      fasting plasma AA concentrations and lower concentrations of TAG, UA, and hsCRP.
      Long-term vegetarians have a better antioxidant status and coronary heart disease
      risk profile than do apparently healthy omnivores. Plasma AA may act a useful
      marker of overall health status.

PMID- 15474874
TI  - Trends in nutritional status and stature among school-age children in Chile.
AB  - OBJECTIVE: We studied the prevalence of weight excess and short stature among
      school-age children in Chile over the past decade. METHODS: We designed a
      descriptive cross-sectional, school-based study to analyze nutritional and
      stature trends in prepubertal and pubertal boys and girls from 1986 to 1998.
      RESULTS: Between 1986 and 1998, we detected significant increases in obesity risk
      (body mass index between the 85th and 95th percentiles): from 8.3% to 19.6% in
      prepubertal males, from 5.4% to 14.6% in pubertal males, from 10.2% to 16.2% in
      prepubertal females, and from 9.7% to 24.9% in pubertal females. Obesity (body
      mass index > 95th percentile) increased significantly, from 4.3% to 29.5% in
      prepubertal males, from 1.6% to 14.6% in pubertal, from 4.7% to 24.0% in
      prepubertal females, and from 2.3% to 17.6% in pubertal females. During this same
      period, the prevalences of short stature (height for age below the 10th
      percentile) decreased from 40.9% to 12.0% in prepubertal males, from 44.2% to
      20.4% in pubertal males, from 29.8% to 12.7% in prepubertal females, and from
      41.1% to 25.8% in pubertal females. CONCLUSIONS: Chile represents a special model
      of fast changes in nutritional and growth trends due to social and political
      interventions and economic development. The significance of these findings in the
      health of Chilean adults and the urgency to implement measures to prevent further
      increases in obesity and simultaneously decrease the prevalence of short stature
      are discussed.

PMID- 15474875
TI  - Meat cooking habits and risk of colorectal cancer in Cordoba, Argentina.
AB  - OBJECTIVE: Colorectal cancer is the third cause of death among women and the
      fifth among men in Cordoba, Argentina. We previously reported colorectal cancer
      to be associated with a high intake of fatty meats and bovine viscera and
      inversely associated with dietary fiber intake. In this study, we investigated
      the role of method of cooking meat and preferences in browned surfaces in the
      risk of colorectal cancer. METHODS: A case-control retrospective study was
      carried out by interviewing 296 patients and 597 control subjects with a food
      frequency questionnaire. Meat consumption and preferred cooking procedures
      (boiled, roasted, barbecued, cooked in a flat iron-pan without fat, and fried)
      were investigated. Odds ratios and 95% confidence intervals were obtained by
      unconditional logistic regression analysis. RESULTS: Barbecuing was the cooking
      method preferred by men, whereas iron-pan cooking was favored by women; frying
      was the least favored method. Fatty beef, sausages, and bovine viscera were
      preferentially barbecued or boiled, whereas lean beef was mainly roasted, iron
      pan cooked, or fried. Chicken was barbecued or roasted. The multivariate relative
      risks (adjusted by age, sex, social stratum, and total energy intake) for
      preferring darkly browned surfaces were significantly associated with an
      increased risk for all cooking procedures (odds ratio, 4.57; 95% confidence
      interval, 3.10 to 6.73). No associations were found for red roasted or for boiled
      meats. CONCLUSION: Increased risk seems to be related to cooking temperature and
      close contact of the food to the heating source, because higher risks were
      observed for heavily browned surfaces when meats were barbecued or iron-pan
      cooked.

PMID- 15474876
TI  - Scholastic achievement: a multivariate analysis of nutritional, intellectual,
      socioeconomic, sociocultural, familial, and demographic variables in Chilean
      school-age children.
AB  - OBJECTIVE: We determined relative effects of nutritional status, intellectual
      ability, exposure to mass media, and socioeconomic, sociocultural, familial,
      demographic, and educational variables on scholastic achievement (SA). METHODS:
      This was a cross-sectional study. Exposure to mass media and nutritional,
      intellectual, socioeconomic, sociocultural, familial, demographic, and
      educational factors, including approximately 2000 variables, were measured in a
      representative and proportional sample of 4509 school-age children from
      elementary and high schools in Chile's Metropolitan Region. The field study was
      carried out between 1986 and 1987, and data processing, which lasted 15 y, was
      completed in 2002. RESULTS: Within the total sample, intellectual ability, level
      of maternal schooling, head circumference-for-age Z score, book reading, in-door
      plumbing, level of paternal schooling, type of school, quality of housing, height
      for-age Z score, and calcium intake were the independent variables with the
      greatest explanatory power in SA variance (r(2) = 0.508). In most grades, IA was
      the independent variable with the greatest explanatory power in SA variance. In
      adolescents in their fourth year of high school and whose physical growth and
      intellectual development processes are consolidated, intellectual ability, age,
      head circumference-for-age Z score, book reading, type of school, and level of
      paternal schooling were the independent variables with the greatest explanatory
      power in SA variance (r(2) = 0.60). CONCLUSIONS: These findings show that SA is
      conditioned by multiple factors depending on the characteristics of school-age
      children, their families, and the educational system. Nutritional indicators of
      past nutrition are significantly associated with SA, especially head
      circumference-for-age Z score. This information may be useful for health and
      educational planning.

PMID- 15474877
TI  - Effects of a nutritional intervention on body composition, clinical status, and
      quality of life in patients with heart failure.
AB  - OBJECTIVES: We assessed the effects of a nutritional intervention on clinical and
      nutritional status and quality of life in patients with heart failure. METHODS:
      Sixty-five patients with heart failure were assigned to one of two groups: the
      intervention group (IG; n = 30) received a sodium-restricted diet (2000 to 2400
      mg/d) with restriction of total fluids to 1.5 L/d, and the control group (CG; n =
      35) received traditional medical treatment and general nutritional
      recommendations. Anthropometric, body composition, physical activity, dietary,
      metabolic, clinical, and quality of life assessments were performed in all
      patients at baseline and 6 mo later. RESULTS: At the end of the study,
      kilocalories, macronutrients, and fluid intakes were significant lower in the IG
      than in the CG. Urinary excretion of sodium decreased significantly in the IG and
      increased in the CG (-7.9% versus 29.4%, P < 0.05). IG patients had significantly
      less frequent edema (37% versus 7.4%, P = 0.008) and fatigue (59.3% versus 25.9%,
      P = 0.012) at 6 mo than at baseline; in addition, functional class improved
      significantly, and no changes were observed in the CG. Extracellular water
      decreased -1.1 +/- 3.7% in the IG and increased 1.4 +/- 4.5% in the CG (P =
      0.03). Physical activity increased 2.5% +/- 7.4% in the IG and decreased -3.1 +/-
      12.0 in the CG (P < 0.05). The IG had a greater increase in total quality of life
      compared with the CG (19.3% versus 3.2%, P = 0.02). CONCLUSIONS: In this study,
      the beneficial effect of a supervised nutritional intervention was proved as part
      of a non-pharmacologic treatment of patients with heart failure, with
      improvements in clinical status and quality of life.

PMID- 15474878
TI  - Response of hemoglobin, serum ferritin, and serum transferrin receptor during
      iron supplementation in pregnancy: a prospective study.
AB  - OBJECTIVE: We evaluated the effect of iron supplementation on biochemical
      indicators of iron status, namely hemoglobin (Hb), serum ferritin (SF), and serum
      transferrin receptor (sTfR), during pregnancy. METHODS: A prospective study was
      conducted in 73 pregnant women who received daily supplements of 60 mg of iron
      and 500 microg of folic acid for 100 d from 19 wk of gestation. The indicators of
      iron status (Hb, SF, and sTfR) at 19, 27, and 35 wk of gestation were analyzed.
      The response of iron status indicators to iron supplementation was assessed in
      the cohort and in pregnant women who were anemic (n = 35) and non-anemic (n = 38)
      at 19 wk. RESULTS: All three indicators of iron status during supplementation (27
      and 35 wk) were similar to the presupplementation status. The sTfR as an
      indicator correlated negatively with presupplementation Hb levels (r = -0.417).
      Based on sTfR level in iron-adequate pregnant women, a cutoff value of at least
      12.0 mg/L was derived to define iron deficiency in pregnancy. When the response
      was tested in anemic pregnant women, iron supplementation improved mean Hb (P <
      0.05) at the end of 35 wk (96 +/- 8.8 to 110 +/- 20.2 g/L) of gestation, with no
      change in SF. Conversely, non-anemic pregnant women showed a significant increase
      in SF and a decrease in Hb (122 +/- 11.6 to 112 +/- 15.2 g/L) at 35 wk of
      gestation. A significant effect of iron intake on sTfR was seen only among iron
      deficient anemic women. CONCLUSIONS: These observations suggest that, during
      pregnancy, sTfR responds to iron supplementation when there is iron-deficiency
      anemia and therefore can be used as an indicator.

PMID- 15474879
TI  - Aerobic endurance, energy expenditure, and serum leptin response in obese,
      sedentary, prepubertal children and adolescents participating in a short-term
      treadmill protocol.
AB  - OBJECTIVE: We analyzed aerobic endurance, energy expenditure, and serum leptin
      concentrations during programmed, short-term exercise in a group of untrained,
      obese children and adolescents. METHODS: This was a prospective, controlled study
      of prepubertal males and females ages 6 to 11 y. Group 1 (n = 40) comprised obese
      children, and group 2 comprised similarly aged non-obese children (n = 16). The
      children completed a stepwise maximal aerobic endurance test (Bruce protocol) on
      a treadmill. The variables measured included anthropometric indexes, serum
      leptin, and physiologic indexes. RESULTS: Maximal oxygen consumption (corrected
      for body weight) values were 29.9 +/- 6.7 mL x kg(-1) x min(-1) in group 1 and
      47.2 +/- 5.3 mL x kg(-1) x min(-1) in group 2 (P < 0.05). The number of exercise
      steps was smaller in group 1 (3.7 +/- 0.7 versus 5.3 +/- 0.4, P < 0.05), as was
      time to exhaustion (9.3 +/- 1.9 min versus 15.1 +/- 1.9 min, P < 0.05). However,
      the energy cost of the exercise did not differ significantly between groups (57.7
      +/- 17.8 kcal versus 65.2 +/- 17.6 kcal), indicating greater energy expenditure
      for less performance in the obese children. Initial leptin concentrations were
      higher in group 1 (24.0 +/- 13.1 ng/mL versus 1.6 +/- 1.7 ng/mL, P < 0.001), and
      exercise did not significantly modify these findings. CONCLUSIONS: Obese children
      were seriously unfit and paid a high energy price for the treadmill test. Initial
      leptin concentrations were very high in the obese children, in the range of
      concentrations found in obese adults. No significant change in leptin
      concentration was observed at the end of the test, probably because of the short
      duration of the activity.

PMID- 15474880
TI  - Insulin secretion in women who have polycystic ovary syndrome and carry the
      Gly972Arg variant of insulin receptor substrate-1 in response to a high-glycemic
      or low-glycemic carbohydrate load.
AB  - OBJECTIVE: We evaluated metabolic parameters in Chilean women with polycystic
      ovary syndrome (PCOS) who were carriers and non-carriers of the glycine-to
      arginine substitution at codon 972 (Gly972Arg) variant of insulin receptor
      substrate-1 and to assess insulin response after oral high- and low-glycemic
      loads METHODS: In 146 women with PCOS and 97 healthy women (HW), Gly972Arg
      genotypes were obtained by polymerase chain reaction, and an oral glucose
      tolerance test was performed with glucose and insulin measurements. An
      insulinogenic index, a homeostasis model assessment for insulin resistance, and
      whole-body insulin sensitivity index (composite) were calculated. Eight carriers
      and eight non-carriers (four PCOS and four HW, respectively) underwent a 50-g
      glucose (high glycemic) or 50-g fructose (low glycemic) load with serum glucose
      and insulin measurements at 15-min intervals for 3 h. RESULTS: The frequency of
      the Gly972Arg variant was higher in PCOS patients than in HW (P < 0.05). The
      insulinogenic index was lower in HW carriers than in non-carriers (P < 0.05). In
      PCOS carriers, 2-h insulin was higher than in those without the mutation. In
      overweight PCOS carriers, the homeostasis model assessment for insulin resistance
      was higher and the insulin sensitivity index was lower than in PCOS patients
      without the mutation. In HW carriers, a delay in the maximal response of insulin
      secretion was observed, with a decrease of 26.7% in insulin concentrations 30 to
      60 min after the 50-g glucose load. Glucose concentrations increased by 19.7%
      between 60 and 120 min. Glucose concentrations between 0 and 120 min were 14.9%
      higher in PCOS carriers than in non-carriers after the 50-g glucose load.
      CONCLUSIONS: In HW, this polymorphism appears to be associated with a decrease in
      insulin secretion; in PCOS women, this polymorphism interacts with obesity to
      influence insulin resistance, thus contributing to the pathogenesis of the
      metabolic component of PCOS.

PMID- 15474881
TI  - Effect of hydroxycitrate on respiratory quotient, energy expenditure, and glucose
      tolerance in male rats after a period of restrictive feeding.
AB  - OBJECTIVE: Recently we demonstrated that hydroxycitrate (HCA) suppresses food
      intake and body weight regain in male rats after substantial body weight loss.
      However, it is not known whether HCA also affects the respiration quotient (RQ),
      energy expenditure (EE), and glucose tolerance in this animal model. METHODS:
      Twenty-four male rats (initial body weight, 378 +/- 3 g) were fed restrictively
      (10 g/d) for 10 d and then given ad libitum access to a high-glucose diet
      supplemented with 3% HCA for 6 d. Controls received the same diet without the
      supplement. RQ and EE were measured during ad libitum days 1, 2, and 6. An oral
      glucose tolerance test was performed on ad libitum day 4 or 5. RESULTS: HCA
      decreased RQ and EE during ad libitum days 1 and 2. In all probability, these
      findings reflect a decrease in de novo lipogenesis. On ad libitum day 6, RQ and
      EE did not differ between treatment groups. HCA suppressed food intake during the
      first 3 d ad libitum, but overall body weight regain was not decreased in the HCA
      group. The oral glucose tolerance test showed that HCA significantly decreased
      the increase in plasma glucose from baseline (Deltaglucose) and tended to
      decrease the area under the curve for glucose. Deltainsulin and area under the
      curve for insulin did not differ between groups. CONCLUSIONS: These results
      indicate that, in this animal model, HCA suppresses de novo lipogenesis.
      Moreover, HCA may improve glucose tolerance.

PMID- 15474882
TI  - Role of dietary fatty acids and acute hyperglycemia in modulating cardiac cell
      death.
AB  - OBJECTIVE: We examined the effect of dietary manipulation of palmitic acid (20%
      [w/w] palm oil [PO]) on cardiomyocyte apoptosis in the rat heart under
      normoglycemic and hyperglycemic conditions in vivo. We used 20% (w/w) sunflower
      oil (SO; a diet rich in omega-6 polyunsaturated fatty acids) as an isocaloric
      control. METHODS: Adult male Wistar rats were fed experimental diets containing
      normal laboratory chow (5% corn oil) or a high fat diet (AIN-76A with PO or SO)
      for 4 wk. Subsequently, to induce diabetes, rats were injected with
      streptozotocin (55 mg/kg, intravenously). After 4 d of diabetes, hearts were
      tested for evidence of lipotoxicity and cell death, and the serum for its related
      markers. RESULTS: Feeding PO and SO magnified palmitic and linoleic acid contents
      within lipoproteins and hearts respectively. Compared with SO, PO diabetic hearts
      demonstrated significantly higher levels of apoptosis, with an altered Bax:Bcl-2
      ratio, augmented lipid peroxidation, and protein modification by formation of
      nitrotyrosine. Interestingly, SO-fed diabetic animals demonstrated an increase in
      serum lactate dehydrogenase and myocardial necrotic changes. CONCLUSION: In
      marked contrast to results obtained in vitro, PO feeding led to only a minor
      fraction of cardiomyocytes undergoing apoptosis and suggests that, in the intact
      heart, protective mechanisms could be triggered that dampen excessive apoptosis.
      Of greater clinical significance was the observation that "heart-friendly"
      vegetable oils such as SO, rich in omega-6 polyunsaturated fatty acids, could
      precipitate cardiac necrosis, and questions its beneficial role in the
      cardiovascular system, especially following diabetes.

PMID- 15474883
TI  - Malnutrition during lactation in rats is associated with higher expression of
      leptin receptor in the pituitary of adult offspring.
AB  - OBJECTIVE: Recent studies have shown that leptin receptor is expressed in human
      and rat pituitary glands. The expression of leptin receptor in rats whose dams
      were malnourished during lactation has not been previously reported. METHODS: We
      examined leptin receptor expression in the pituitary gland of adult rats whose
      dams were assigned to one of the following groups during lactation: control diet,
      protein-restricted diet (8% protein), or energy-restricted diet (the control diet
      fed in restricted quantities that were calculated according to the mean ingestion
      of the protein-restricted group). After weaning, all pups had free access to the
      control diet until they reached adult age, at which time leptin receptor
      expression in the pituitary was analyzed by immunohistochemistry. RESULTS: Adult
      animals from protein- and energy-restricted dams had a higher expression of
      leptin receptor in pituitary tissue, normal serum leptin concentrations, higher
      serum tri-iodothyronine concentrations, and lower thyroid-stimulating hormone
      concentrations than did the control rats. CONCLUSIONS: In the fed state, leptin
      has a stimulatory effect on release of thyroid-stimulating hormone. The higher
      expression of leptin receptor in the pituitary of animals from protein- and
      energy-restricted dams may suggest a postreceptor failure in leptin action. This
      higher receptor expression may have allowed a greater inhibition of release of
      thyroid-stimulating hormone.

PMID- 15474884
TI  - Soymilk intake is associated with plasma and liver lipid profiles in rats fed a
      high-cholesterol diet.
AB  - OBJECTIVE: This study investigated the effects of soymilk on lipid metabolism in
      Sprague-Dawley rats fed a cholesterol-enriched (0.3%) diet. METHODS: Thirty male
      Sprague-Dawley rats weighing 230.0 +/- 9.8 g were randomly assigned to one of
      three groups: control, S1 (containing 15% soymilk powder in the diet), and S2
      (22.5%). After 8 wk, lipid profiles of the plasma, liver, and feces were
      determined. RESULTS: Body weight gain, daily food intake, and feeding efficiency
      showed no differences across groups (P > 0.05). The experimental groups had
      significantly lower plasma levels of cholesterol, triacylglycerol, and low
      density lipoprotein cholesterol than the control group (P < 0.05) at weeks 4 and
      8. However, total fecal excretion of neutral steroid did not significantly differ
      across groups (P > 0.05). CONCLUSION: Soymilk affects the metabolism of plasma
      cholesterol in Sprague-Dawley rats.

PMID- 15474885
TI  - Alanyl-glutamine hastens morphologic recovery from 5-fluorouracil-induced
      mucositis in mice.
AB  - OBJECTIVE: In this study, we postulated the beneficial role of oral alanyl
      glutamine, a more stable glutamine derivative to decrease 5-fluorouracil (5-FU)
      induced mucositis in mice. METHODS: We measured different morphologic parameters
      to assess structural changes over time in the small bowel, including crypt depth,
      villus height, villus area, mitotic and apoptotic indices at the crypt level
      using terminal deoxyuridine triphosphate nick end labeling, and hematoxylin-eosin
      staining of ileal tissue. In addition, we analyzed the effect of different alanyl
      glutamine concentrations on animal weight curves after 5-FU treatment. RESULTS:
      Neither glutamine nor alanyl- glutamine prevented the 5-FU intestinal structural
      damage or apoptosis in crypt enterocytes at 24 h after 5-FU challenge. However,
      we found that alanyl-glutamine, but not glutamine, speeds intestinal recovery
      when compared with 5-FU-treated controls (P < 0.05), predominantly by enhancing
      mitotic activity and crypt length. CONCLUSION: Our findings provide important
      data to support clinical studies of oral alanyl-glutamine in 5-FU-induced
      mucositis.

PMID- 15474886
TI  - Essential fatty acids in Huntington's disease.
AB  - Huntington's disease is an inherited neurodegenerative disorder due to a mutation
      in exon 1 of the Huntingtin gene that encodes a stretch of polyglutamine (polyQ)
      residues close to the N-terminus of the huntingtin protein. Aggregated polyQ
      residues are highly toxic to the neuronal cells when they enter the cell nucleus.
      The mechanisms by which aggregated polyQ induces neurodegeneration include the
      binding of abnormal huntingtin to cyclic adenosine monophosphate response element
      binding protein, which hampers its ability to turn on transcription of other
      genes; mutant huntingtin binding to the active site on the cyclic adenosine
      monophosphate response element binding protein, which is essential for its
      acetyltransferase activity and, hence, the drugs that inhibit histone deacetylase
      arrest polyQ-dependent neurodegeneration; and/or disrupting the ubiquitin
      proteasome system. Transgenic R6/1 mice that incorporate a human genomic fragment
      containing promoter elements exon 1 and a portion of intron 2 of the huntingtin
      gene responsible for Huntington's disease develop late-onset neurologic deficits
      in a manner similar to the motor abnormalities of Huntington's disease and show
      increased survival rates and decreased neurologic deficits when supplemented with
      essential fatty acids throughout life. A randomized, placebo-controlled, double
      blind study has shown that highly unsaturated fatty acids are beneficial to
      patients with Huntington's disease. These results raise the possibility that
      unsaturated fatty acids may prevent or arrest polyQ aggregation, inhibit histone
      deacetylase, and/or activate the ubiquitin-proteasome system. In view of the
      encouraging results with essential fatty acids in Huntington's disease, it is
      proposed that their possible use in other neurodegenerative conditions need to be
      explored.

PMID- 15474887
TI  - Surveys: are they trustworthy?

PMID- 15474888
TI  - Xhooxham, the young lady of a Bushman tribe, and "globesity".

PMID- 15474889
TI  - The trustworthiness of surveys.

PMID- 15474890
TI  - Need of complementary therapy with selenium in asthmatics.

PMID- 15474891
TI  - Assessment of iodine levels in the Pakistani diet.

PMID- 15474892
TI  - Atypical antipsychotics and glucose dysregulation: a systematic review.
AB  - Atypical antipsychotics (AAP) have been widely used for the management of
      patients with schizophrenia and other psychotic disorders since they were
      introduced during the past decade. AAP, as a class, have demonstrated a
      significant advantage over conventional antipsychotics in clinical efficacy and
      lower incidence of extrapyramidal symptoms (EPS) and tardive dyskinesia (TD).
      However, there have been numerous case reports, retrospective studies,
      epidemiological and clinical data suggesting that certain AAP may be associated
      with a greater risk of metabolic abnormalities than others, including weight
      gain, hyperlipidemia, and new-onset type 2 diabetes mellitus (DM) or diabetic
      ketoacidosis (DKA). In this article, we review and evaluate recent findings
      addressing the issue of glucose dysregulation associated with AAP therapy along
      with the recommendations with a recent consensus conference on this issue.
      Rational patient monitoring guidelines are also elucidated, particularly for high
      risk populations that need more intensive scrutiny during treatment of AAP.

PMID- 15474893
TI  - The persistence of developmental markers in childhood and adolescence and risk
      for schizophrenic psychoses in adult life. A 34-year follow-up of the Northern
      Finland 1966 birth cohort.
AB  - Childhood precursors of schizophrenia include multiple abnormalities of
      development. Continuities between early and subsequent deviance are poorly
      characterised. We studied associations among premorbid developmental deviance
      using data at ages 1 year (learning to stand, walk, and speak, attainment of
      bladder and bowel control) and 16 years (success at school). Generalised linear
      modelling was used to examine differential linear associations and trends across
      adult psychiatric diagnoses. In babies who, as adults, suffered schizophrenia or
      any psychosis, those who learned to stand latest were also more likely to perform
      poorly at school in both motor and theoretical domains at age 16 when compared
      with earlier learners. The effect was independent of genetic and perinatal
      factors. We conclude that the early developmental deviation in the first year of
      life is associated with lower school performance at age 16. Developmental
      continuity among children who develop psychoses was stronger than among normal
      controls and those hospitalized for nonpsychotic psychiatric disorder. These
      findings are in line with the hypothesis that a neural diathesis is present
      during postnatal brain development before schizophrenia. This supports the
      longitudinal dimension and life span models of schizophrenia.

PMID- 15474894
TI  - Risk factors for transition to first episode psychosis among individuals with 'at
      risk mental states'.
AB  - Recently developed criteria have been successful at identifying individuals at
      imminent risk of developing a psychotic disorder, but these criteria lead to 50
      60% false positives. This study investigated whether measures of family history,
      peri-natal complications, premorbid social functioning, premorbid personality,
      recent life events and current symptoms would be able to improve predictions of
      psychosis in a group of young, help-seeking individuals who had been identified
      as being at risk. Individuals (N=74) were followed up at least 1 year after
      initial assessment. Half the sample went on to develop a psychotic disorder. The
      most reliable scale-based predictor was the degree of presence of schizotypal
      personality characteristics. However, individual items assessing odd
      beliefs/magical thinking, marked impairment in role functioning, blunted or
      inappropriate affect, anhedonia/asociality and auditory hallucinations were also
      highly predictive of transition, yielding good sensitivity (84%) and specificity
      (86%). These predictors are consistent with a picture of poor premorbid
      functioning that further declines in the period up to transition.

PMID- 15474895
TI  - Effects of D-cycloserine on negative symptoms in schizophrenia.
AB  - INTRODUCTION: The negative and cognitive symptoms of schizophrenia are poorly
      responsive to neuroleptic treatment. Glutamatergic dysfunction may mediate some
      of these symptoms. Low dose D-cycloserine (DCS) is a partial agonist at the
      glycine site of the NMDA-associated receptor complex, noncompetitively enhancing
      NMDA neurotransmission. Prior studies suggest a beneficial effect of DCS on
      negative symptoms and cognition. This treatment trial was initiated to confirm
      and extend these findings. METHODS: Twenty-two male schizophrenic subjects
      displaying prominent negative symptoms who were stabilized on typical
      neuroleptics completed the study. A randomized double-blind parallel group design
      was used to compare the effects of 50 mg p.o. QD of DCS to placebo over 4 weeks.
      The two subject groups did not differ significantly in age, age of onset of
      illness or time on current neuroleptic treatment. Symptoms were rated by means of
      the SANS, BPRS and Abrams and Taylor rating scale. Cognition was assessed with
      the Sternberg Memory Test and the Continuous Performance Test. RESULTS: Both
      medication groups improved over the 4 weeks of treatment. However, there were no
      significant differences between the DCS and placebo group on any symptom rating.
      DCS effects on cognition did not differ from placebo. DISCUSSION: This study did
      not detect improvement in negative symptoms or cognitive performance with DCS
      treatment that has been found in some prior studies. This negative finding may be
      attributed to small sample size, relatively short duration of treatment and the
      overall modest effect of DCS. Future studies of DCS should be adequately powered
      to detect a small to medium effect size and should provide for a longer treatment
      phase than was used in this study in order to avoid a type II error.

PMID- 15474896
TI  - Cingulate gyrus volume and metabolism in the schizophrenia spectrum.
AB  - BACKGROUND: The cingulate gyrus, which is involved in affect, attention, memory
      and higher executive functions, has been implicated as a dysfunctional region in
      schizophrenia. Postmortem studies report cytoarchitectural changes in the
      anterior cingulate gyrus (ACG) and functioning imaging studies show correlations
      between the degree of hypometabolism of the anterior cingulate and clinical
      symptoms in schizophrenia. METHODS: Unmedicated patients with schizophrenia
      (n=27) and schizotypal personality disorder (SPD) (n=13), as well as sex- and age
      matched control subjects (n=32), were studied with (18)F-fluorodeoxyglucose
      positron emission tomography (PET) scans and magnetic resonance imaging (MRI). As
      a control over mental activity, all subjects performed a verbal working memory
      task during the PET protocol. The cingulate gyrus was first outlined on the MRI
      scans and, after coregistration, the coordinates were applied to the PET scans to
      yield a three-dimensional metabolic map of the cingulate gyrus for each subject.
      A statistical resampling method was used to analyze the metabolic differences
      between groups. RESULTS: Compared with controls, patients with schizophrenia had
      lower relative glucose metabolic rates in the left anterior cingulate and the
      right posterior cingulate gyrus (PCG) assessed by 3-D significance probability
      mapping. SPD patients had higher glucose metabolic rates (GMRs) in the left
      posterior cingulate than did controls. Furthermore, volumetric measurement with
      MRI showed the left anterior cingulate and Brodmann area 24' to be smaller in
      schizophrenic patients than controls. CONCLUSIONS: Compared with controls,
      patients with schizophrenia have metabolic and volumetric reductions in a
      cingulate gyrus area that is related to higher executive functions. Schizotypal
      patients rely more on sensory association areas to perform a cognitive task than
      do controls and seem to be a group that is partially distinct in its
      physiological and functional characteristics.

PMID- 15474897
TI  - Decreased nonlinear complexity and chaos during sleep in first episode
      schizophrenia: a preliminary report.
AB  - Schizophrenia is characterized by disturbed sleep architecture. It has been
      thought that sleep abnormalities may underlie information processing deficits
      associated with this disorder. Nonlinear analyses of sleep data can provide
      valuable information on sleep characteristics that may be relevant to the
      functions of sleep. This study examined the predictability and nonlinear
      complexity of sleep EEG time series in two EEG channels (C4 and F4) using
      measures of nonlinearity, such as symbolic dynamics and the largest Lyapunov
      exponent (LLE) in schizophrenia. A series of antipsychotic naive patients with
      first episode of schizophrenia or schizoaffective disorder and age-matched
      healthy controls were studied during awake period, stage 1/2, slow wave sleep
      (stage 3/4) and rapid eye movement (REM) sleep. Nonlinearity scores were
      significantly lower during awake stage in patients compared to controls
      suggesting that there may be a diminished interplay between various parameters
      for the genesis of waking EEG. Symbolic dynamics and LLE were significantly lower
      in patients during REM compared to healthy controls, suggesting decreased
      nonlinear complexity of the EEG time series and diminished chaos in
      schizophrenia. Decreased nonlinear complexity was also correlated with
      neurocognitive deficits as assessed by the Wisconsin card sorting test.
      Diminished complexity of EEG time series during awake and REM sleep in patients
      with schizophrenia may underlie the impaired ability to process information in
      psychotic disorders such as schizophrenia.

PMID- 15474898
TI  - A brief cognitive assessment for use with schizophrenia patients in community
      clinics.
AB  - Cognitive impairment is a prominent feature of schizophrenia. The availability of
      very brief measures may increase the use of cognitive assessment in routine care
      settings. We examined the reliability and validity of the brief cognitive
      assessment (BCA), a battery that takes approximately 15 min to administer and
      score, and that was designed to be sensitive to changes in cognition with novel
      antipsychotics. The BCA was administered to 340 outpatients on two occasions, 3
      months apart. A sub-sample of subjects received a full battery of cognitive tests
      (n=97) and additional measures of functional outcome. Results indicated that the
      BCA had very good test-retest reliability and inter-item consistency. Moreover,
      the BCA was strongly correlated with a comprehensive battery (r=0.72; p<0.0001)
      which took 8 to 10 times longer to administer. Finally, both cognitive batteries
      were correlated similarly with measures of community functioning. Changes over
      time for individual patients can be interpreted in the context of normative data
      available for each test in the BCA. The data provide preliminary evidence for the
      reliability and validity of the BCA. Further studies examining the utility of the
      BCA for tracking changes in cognitive functioning with treatment are encouraged.

PMID- 15474899
TI  - Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis.
AB  - BACKGROUND: Schizophrenia is characterized by a generalized cognitive impairment
      with pronounced deficits in the domains of verbal memory, executive functioning
      and attention. AIM: To investigate whether cognitive deficits found in patients
      with schizophrenia are also found in non-affected relatives. METHOD: A meta
      analytic review of the published literature on cognitive performance between
      relatives of schizophrenic patients and healthy controls. RESULTS: The meta
      analyses yielded nine weighted effect sizes from 37 studies comprising 1639
      relatives of schizophrenia patients and 1380 control subjects. The largest
      differences were found on verbal memory recall (d=0.54, 95% CI=0.43-0.66) and
      executive functioning (d=0.51, 0.36-0.67). Attentional functioning showed smaller
      effect sizes (d=0.28, 0.06-0.50). These effect sizes are in the moderate range.
      CONCLUSION: Cognitive deficits found in patients with schizophrenia are also
      found in non-affected relatives. This finding is consistent with the idea that
      certain cognitive deficiencies in relatives are caused by familial predisposition
      to schizophrenia and that these deficiencies might be putative endophenotypes for
      schizophrenia. However, our results do not address genetic causes directly.
      Further work is needed to determine whether certain cognitive traits are familial
      and whether there is co-inheritance of these traits with schizophrenia within
      families.

PMID- 15474900
TI  - Measuring cognitive insight in middle-aged and older patients with psychotic
      disorders.
AB  - The study examined the psychometric properties, factor structure and validity of
      a recently developed measure of insight, the Beck Cognitive Insight Scale (BCIS)
      and tested the relationship between the BCIS and psychiatric symptoms in a sample
      of middle-aged and older patients with schizophrenia or schizoaffective disorder.
      The BCIS measures the ability of respondents to observe and question their
      cognitive processes, whereas other insight scales focus primarily on knowledge
      about the presence of an illness and need for treatment. Participants were 164
      middle-aged and older outpatients with schizophrenia or schizoaffective disorder
      who completed a battery of measures assessing insight, symptoms of schizophrenia
      and symptoms of depression. The results of a confirmatory factor analysis (CFA)
      supported the two-factor structure previously reported for the BCIS, with one
      factor labeled self-reflectiveness and the other labeled self-certainty. The BCIS
      showed adequate reliability and a moderate correlation with the Birchwood Insight
      Scale (IS). The BCIS correlated with some PANSS subscales measuring symptoms of
      schizophrenia, but did not correlate at a significant level with symptoms of
      depression. The findings suggest that middle-aged and older outpatients with
      schizophrenia or schizoaffective disorder respond on the BCIS in a manner similar
      to a younger inpatient population. This instrument is a promising tool for
      measuring the role of cognitive change in a broad range of patients experiencing
      psychosis.

PMID- 15474902
TI  - Neuropsychological correlates of symptom profiles in first episode schizophrenia.
AB  - This paper aimed to examine the relationship between the trichotomous symptom
      structure of psychopathology and neuropsychological functioning in young people
      with first episode schizophrenia (FES), most of whom were receiving atypical
      antipsychotic medication. This was with a view to providing insight into the
      underlying pathophysiology of the clinical symptoms of schizophrenia. Fifty-three
      young people (aged 13-25 years) with FES participated in the study. Subjects
      completed a comprehensive clinical and neuropsychological examination. Cognitive
      domain scores were correlated with composite scores relating to Disorganisation,
      Psychomotor Poverty and Reality Distortion. A significant association was
      identified between Disorganisation and Verbal Acquisition, Verbal Recall and
      Cognitive Flexibility. There were no significant associations between cognitive
      domains and either Reality Distortion or Psychomotor Poverty, nor with measures
      of depressive symptomatology. The present study provides preliminary evidence
      that symptoms associated with the Disorganisation factor are significantly
      associated with cognitive deficits suggesting impaired frontal-temporal
      functioning. Differences between the current findings and those of similar
      research may reflect the effects of different medication regimes, as well as the
      absence of illness chronicity.

PMID- 15474901
TI  - Heterogeneity of schizophrenia: a study of individual neuropsychological
      profiles.
AB  - Based on a strategy developed by Seidman et al. (Seidman, L.J., Faraone, S.V.,
      Kremen, W.S., Pepple, J.R., Lyons, M.J., Tsuang, M.T., 1993. Neuropsychological
      dysfunctions in the non-psychotic first-degree relatives of schizophrenic
      patients, Poster presented at the annual meeting of the Society for Research and
      Psychopathology. Chicago, IL) we examined neuropsychological heterogeneity in
      schizophrenia using clinical neuropsychological descriptions of individual cases
      as the starting point. We blindly rated neuropsychological profiles of 74
      schizophrenia patients and 91 normal controls based primarily on prototypes from
      the clinical literature in neuropsychology. Patients were classified as having
      the following profile types: within normal limits (WNL) (23%, n=17),
      frontal/abstraction (46%, n=34), widespread/diffuse (14%, n=10), left
      temporal/verbal memory (8%, n=6) and other (9%, n=7). As expected based on our
      classification scheme, the groups had different profile shapes (group x function
      interactions). They were also significantly different from one another in terms
      of overall severity (main effects); however, severity differences were not
      inherent in the definition of all groups. Longer duration of illness and greater
      overall cognitive impairment were observed as one went from the left temporal to
      the frontal to the widespread groups. Longitudinal studies are needed to
      determine whether the different neuropsychological profiles reflect true subgroup
      differences or within-person change over time. Further research-probably
      including neuroimaging and genetic studies-will also be needed to determine the
      validity and the utility of this strategy for identifying neuropsychological
      profile types.

PMID- 15474903
TI  - Self-awareness of cognitive functioning in schizophrenia.
AB  - Poor awareness of psychiatric symptoms is associated with schizophrenia. It is
      unclear whether this lack of insight extends to the cognitive impairment that
      affects at least 85% of people with schizophrenia. Given the increasing efforts
      to develop treatments for cognitive impairment, and the link between awareness of
      disability and treatment compliance, it is important to understand whether people
      with schizophrenia have awareness of their cognitive deficits. Ratings of
      cognitive functioning from 185 outpatients diagnosed with schizophrenia, their
      clinicians' ratings and objective neuropsychological test results were compared
      in the following cognitive domains: attention, nonverbal memory, and verbal
      memory. The results indicated that there was poor concordance among the three
      assessments. Patients did not agree with their clinician's assessments and did a
      very poor job of accurately classifying their cognitive status. However,
      clinicians were also poor at classifying cognitive status consistent with
      neuropsychological test results. The implications of these findings for
      understanding insight in schizophrenia are discussed.

PMID- 15474904
TI  - Verbal memory processes in schizophrenia patients and biological relatives of
      schizophrenia patients: intact implicit memory, impaired explicit recollection.
AB  - Verbal memory deficits are arguably the most common cognitive abnormalities in
      biological relatives of schizophrenia patients. Because verbal memory is a
      complex cognitive function, it is necessary to differentiate its intact and
      compromised aspects in order to reveal aberrant neural systems that reflect
      genetic risk in relatives of schizophrenia patients. Using an experimental verbal
      memory task, we examined encoding, free-recall, repetition priming, and
      recognition of verbal material in 22 schizophrenia patients, 22 first-degree
      biological relatives of schizophrenia patients, and 23 nonpsychiatric control
      participants. Schizophrenia patients exhibited intact repetition priming, but
      worse size judgment task performance (encoding), recall, and recognition than the
      control participants. Biological relatives of schizophrenia patients exhibited
      intact size judgment task performance, repetition priming, and recognition, but a
      free-recall deficit. Although size judgment task performance at encoding was
      associated with recall of verbal material in schizophrenia and control groups, in
      the relative group encoding performance was associated with the degree of
      repetition priming. Findings are consistent with impaired explicit recollection
      of verbal material, but intact implicit verbal memory in schizophrenia patients
      and biological relatives of schizophrenia patients.

PMID- 15474905
TI  - Follow-up MRI study of prefrontal volumes in first-episode psychotic patients.

PMID- 15474906
TI  - Meta-analyses of the association between genetic polymorphisms of neurotrophic
      factors and schizophrenia.
AB  - Based on the neurodevelopmental hypothesis of schizophrenia, neurotrophic factors
      (NTFs) may be involved in its pathogenesis. Previous association studies between
      schizophrenia and neurotrophic factors have shown inconsistent results, which
      might be due to the heterogeneity and small sample size of the studies. To reach
      a conclusive understanding of the association, we used a meta-analytic method to
      study the association of schizophrenia with the polymorphisms in two candidate
      genes, ciliary neurotrophic factor (CNTF) and neurotrophin 3 (NT3). In our study,
      two meta-analyses were performed. One included eight studies examining the
      association of schizophrenia with the A3 allele in a dinucleotide repeat
      polymorphism of the NT3 gene promoter (N=1938). The other was employed in nine
      studies examining the association with a null mutation of the CNTF gene (N=2393).
      Neither of these analyses provided evidence for association. However, our sub
      analyses showed a trend of association between the NT3 polymorphism and
      schizophrenics in Japanese, as well as an association between the CNTF null
      mutation and schizophrenics without psychiatric family history. These results
      suggested that the variations at the NT3 and the CNTF genes do not influence the
      schizophrenia risk, but a role in the susceptibility of subgroups of the patients
      cannot be excluded.

PMID- 15474907
TI  - NR3A NMDA receptor subunit mRNA expression in schizophrenia, depression and
      bipolar disorder.
AB  - Growing evidence suggests that NMDA receptor (NMDAR) dysfunction may be involved
      in schizophrenia. The NMDAR is a multimeric assembly derived from seven different
      genes (NR1, NR2A-2D and NR3A-3B). While region-specific changes in the expression
      of most NMDAR subunits have been reported in schizophrenia, possible
      abnormalities of NR3A expression have not been investigated. Both
      electrophysiological and anatomical data in rodents, however, suggest that NR3A
      subunits could play a role in this disorder. In this study, we measured NR3A
      transcript levels in the dorsolateral prefrontal cortex (DLPFC) and inferior
      temporal neocortex in the brains of people with schizophrenia, bipolar disorder,
      depression, and a comparison group. This transcript was elevated by 32% in
      schizophrenia relative to controls, but only in the DLPFC and not inferior
      temporal cortical regions. Interestingly, this effect was restricted to gyral
      aspects of the DLPFC and did not involve sulcal areas. NR3A mRNA was
      significantly decreased by 12% in bipolar disorder relative to the comparison
      group in DLPFC, although there were no gyral versus sulcal differences. As was
      the case in schizophrenia, no changes in NR3A expression were observed in the
      inferior temporal cortex in bipolar disorder. These data indicate that the NR3A
      subunit is abnormally expressed in both schizophrenia and bipolar disorder.

PMID- 15474908
TI  - Dopamine transporter density in schizophrenic subjects with and without tardive
      dyskinesia.
AB  - Striatal dopamine transporter (DAT) binding potential (BP) was compared between
      schizophrenic subjects with and without tardive dyskinesia and controls. Although
      the groups were not statistically different in striatal BP, tardive subjects had
      apparently lower DAT density than non-tardive schizophrenic subjects. Significant
      and trend-level inverse correlations were found between DAT BP in the striatum,
      and especially the severity of negative symptom scores, but also cognitive, and
      depression/anxiety scores on the PANSS.

PMID- 15474909
TI  - GSK-3 parameters in postmortem frontal cortex and hippocampus of schizophrenic
      patients.
AB  - The protein kinase glycogen synthase kinase-3 (GSK-3) is highly abundant in brain
      and involved in signal transduction cascades, particularly during
      neurodevelopment. We have previously found reduced GSK-3beta mRNA levels, protein
      levels and GSK-3 total (alpha+beta isoforms) activity in postmortem frontal
      cortex of schizophrenic patients in the Stanley Medical Research Institute's
      Brain Collection. To verify and extend these findings, GSK-3 parameters were now
      measured in the frontal cortex (BA9) and hippocampus obtained from the Rebecca L.
      Cooper Research Laboratories postmortem brain collection. Fifteen pairs of
      schizophrenic patients and matched control subjects have been studied. No
      significant differences in GSK-3alpha and GSK-3beta mRNA levels, GSK-3beta
      protein levels or total GSK-3 (alpha+beta) activity were found in the frontal
      cortex of the two diagnostic groups. Hippocampal GSK-3alpha and GSK-3beta mRNA
      levels were significantly lower (22% and 28%, respectively) in the tissue from
      the schizophrenic patients compared with the normal controls. Hippocampal GSK
      3beta protein levels in the schizophrenic patients were 24% significantly lower
      than control values only after omission of three outlier subjects. Hippocampal
      total GSK-3 (alpha+beta) activity in the patients was 31% lower in the
      schizophrenic patients vs. control subjects. This difference was marginally
      significant. While our previous data on GSK-3beta in postmortem brain and the
      recent report that there is impaired AKT1-GSK-3beta signaling in schizophrenia
      suggest that changes in pathways involving protein kinases such as AKT1 and GSK
      3beta in schizophrenia are complex, our present data do not provide strong
      evidence in support of the involvement of GSK-3beta in schizophrenia. Therefore,
      further investigation in a greater number of brain samples is warranted to better
      clarify the possible role of this enzyme in the pathophysiology of schizophrenia.

PMID- 15474910
TI  - Hippocampal 5-hydroxytryptamine receptors: abnormalities in postmortem brain from
      schizophrenic subjects.
AB  - There is strong evidence that hippocampal 5-hydroxytryptamine (5-HT) systems are
      affected in schizophrenia and hence we have studied a number of markers of the 5
      HT system in hippocampi from subjects with schizophrenia. Using in situ
      radioligand binding with autoradiography we measured [(3)H]proplyamino-8-hydroxy
      1,2,3,4-tetrahydronapthalene, [(3)H]ketanserin and [(3)H]sumatriptan binding in
      hippocampi from 20 schizophrenic and 20 control subjects. There were significant
      decreases in the density of [(3)H]ketanserin binding to the 5-HT(2A) receptor (5
      HT(2A)R) in the Cornu Ammonis (CA) 3 (p=0.006), CA 1 (stratum radiatum p=0.02;
      pyramidal layer p=0.0008) and subiculum (pyramidal layer p=0.0004), as well as
      methiothepin-insensitive [(3)H]sumatriptan binding to the 5-HT(1F)R in the CA 1
      (p=0.016), stratum radiatum/lacunosum moleculare (p=0.04) and subiculum (p=0.015)
      from subjects with schizophrenia. There were no differences in the densities of 5
      HT(1A)R, 5-HT(1D)R or 5-HT(4)R in hippocampi from subjects with schizophrenia.
      These data support the hypothesis that regionally specific reductions in the
      density of the 5-HT(2A)R and 5-HT(1F)R are a component of the pathological
      processes underlying schizophrenia.

PMID- 15474911
TI  - An electrophysiological (ERP) component, the recognition potential, in the
      assessment of brain semantic networks in patients with schizophrenia.
AB  - Abnormal activation of semantic networks may be the underlying basis for thought
      disorder (ThD) in patients with schizophrenia. However, whether this abnormality
      consists of increased or decreased activation is unclear. Previous behavioral and
      electrophysiological (N400) data have failed to yield consistent evidence for
      clarifying this hypothesis. One of the event-related potentials (ERP) components
      (the recognition potential, RP), presumably reflecting activation of specific
      semantic networks involved in ThD, has not been used to studies of schizophrenia,
      and may add additional information to support or refute this hypothesis. In an
      initial experiment, RP amplitude was reduced in schizophrenic patients, but
      particularly in those with ThD. In a second experiment, in addition to reduced
      overall RP amplitude, concrete words were shown to have higher amplitudes than
      abstract words in both patients and controls, supporting a relative integrity of
      the lexicon in ThD patients. RP reduction suggests that a fewer number of
      networks' elements are activated when an incoming word is processed, thus
      supporting hypoactivation of the semantic networks as the basis for ThD.

PMID- 15474912
TI  - A developmental model for similarities and dissimilarities between schizophrenia
      and bipolar disorder.
AB  - Schizophrenia and mania have a number of symptoms and epidemiological
      characteristics in common, and both respond to dopamine blockade. Family, twin
      and molecular genetic studies suggest that the reason for these similarities may
      be that the two conditions share certain susceptibility genes. On the other hand,
      individuals with schizophrenia have more obvious brain structural and
      neuropsychological abnormalities than those with bipolar disorder; and pre
      schizophrenic children are characterised by cognitive and neuromotor impairments,
      which are not shared by children who later develop bipolar disorder. Furthermore,
      the risk-increasing effect of obstetric complications has been demonstrated for
      schizophrenia but not for bipolar disorder. Perinatal complications such as
      hypoxia are known to result in smaller volume of the amygdala and hippocampus,
      which have been frequently reported to be reduced in schizophrenia; familial
      predisposition to schizophrenia is also associated with decreased volume of these
      structures. We suggest a model to explain the similarities and differences
      between the disorders and propose that, on a background of shared genetic
      predisposition to psychosis, schizophrenia, but not bipolar disorder, is subject
      to additional genes or early insults, which impair neurodevelopment, especially
      of the medial temporal lobe.

PMID- 15474913
TI  - The retrospective measurement of prenatal and perinatal events: accuracy of
      maternal recall.
AB  - Adverse obstetric events have been implicated as risk factors for schizophrenia.
      Many studies have relied on retrospective recall of these events, given typical
      adult onset of schizophrenia, when most studies ascertain their samples. The goal
      of this study was to assess the validity of an interview for the long-term recall
      of prenatal and perinatal events. Ninety-six women from the Providence and Boston
      cohorts of the National Collaborative Perinatal Project were administered a brief
      structured telephone interview regarding their recall of pregnancy-related events
      that had occurred 22 years or more prior to interview. Women accurately reported
      major medical events such as cesarean section, breech delivery, and multiple
      birth (kappa=1) and demographic items, such as age at birth and parity. Medical
      interventions and major medical conditions such as placental (kappa=-0.01) and
      cord (kappa=-0.10) difficulties were not accurately reported. Estimated
      birthweight, low birthweight, and length of gestation were recalled with
      reasonable accuracy. Women who completed high school generally recalled events
      more accurately than those who did not. It is therefore important to attend to
      the sources of information, the mode of interviewing, the specific type of event,
      and sociodemographic characteristics of the informant to improve the accuracy of
      retrospective data on obstetric events, and to increase the validity of findings
      relating these to the onset of schizophrenia.

PMID- 15474914
TI  - Increased circulatory dehydroepiandrosterone and dehydroepiandrosterone-sulphate
      in first-episode schizophrenia: relationship to gender, aggression and
      symptomatology.
AB  - Dehydroepiandrosterone (DHEA) is a major circulating neurosteroid in humans and
      its administration has demonstrated efficacy in the improvement of mood, with
      increased energy, interest, confidence and activity levels. Since recent findings
      have suggested the role of neurosteroids in general, and DHEA in particular, in
      the symptomatology and pharmacotherapy of schizophrenia patients with chronic
      illness, we investigated DHEA and DHEA-S blood levels in individuals in their
      first-episode of psychosis in order to exclude effects of age, chronic illness,
      long-term treatment and institutionalization. Blood levels for DHEA, DHEA-S and
      cortisol were obtained for 37 first-episode schizophrenia subjects and 27 normal
      age- and sex-matched controls and correlated with a range of clinical and side
      effect rating scales. Baseline DHEA and DHEA-S levels were significantly higher
      in schizophrenia patients (p<0.05 and p<0.001, respectively). No gender
      differences were noted in DHEA levels; however, DHEA-S levels were significantly
      higher in male patients. DHEA-S levels inversely correlated with severity of
      illness (p<0.05) and aggressive behavior (p<0.05). Patients with higher DHEA-S
      levels tended to have shorter hospitalizations. Results suggest that individuals
      in their first-episode of schizophrenia psychosis may develop a neurosteroid
      response to the first onset of psychosis, which may be associated with a
      reduction in various adverse clinical features including aggression. Such a
      putative mechanism may become desensitized with the onset of chronic illness.
      While preliminary, these results further imply the role of these neurosteroids in
      the pathophysiology and management of schizophrenia.

PMID- 15474915
TI  - Use of antipsychotic medications among HIV-infected individuals with
      schizophrenia.
AB  - Persons with schizophrenia face elevated risk of infection with HIV. While HIV
      therapy is demanding, patients diagnosed with both conditions also require
      appropriate and consistent management of their psychiatric illness, for the same
      reasons that generally apply to persons with schizophrenia and because untreated
      psychiatric illness can interfere with full participation in HIV care. This study
      examines the correlates of use of and persistence on antipsychotic medications
      among HIV-infected individuals with schizophrenia, using merged New Jersey
      HIV/AIDS surveillance data and paid Medicaid claims. Persistence was defined as
      at least 2 months of medication use in a quarter. We identified 350 individuals
      who were dually diagnosed with HIV and schizophrenia. Overall, 81% of these
      beneficiaries had at least one claim for an antipsychotic medication at some
      point between 1992 and 1998. Multivariate techniques were used, including simple
      logistic regressions on use and robust longitudinal regressions that controlled
      for repeated observations on the same individual and treatment gaps. Among users
      of antipsychotic medications, persistence was very low at 37%. Racial/ethnic
      minorities were less likely to receive atypical antipsychotic medications. Use of
      atypical antipsychotics was associated with higher persistence. Our study
      confirmed past findings of racial disparities in the receipt of atypical
      antipsychotic medications. Findings suggest that use of atypical medications may
      benefit individuals dually diagnosed with HIV and serious mental illness.

PMID- 15474916
TI  - Cost-effectiveness analysis of pharmacological treatments in schizophrenia:
      critical review of results and methodological issues.
AB  - OBJECTIVE: To comprehensively review and critically appraise the results and the
      methodological issues in the cost-effectiveness literature on pharmacological
      treatments in schizophrenia. METHODS: Relevant literature published in peer
      reviewed journals was identified through a computer search in Medline from 1975
      to 2002. Further studies were identified using reference lists and published
      review articles. Articles included in the review were required to evaluate both
      costs and clinical outcomes in the same study. RESULTS: Seventeen articles met
      all inclusion criteria. Cost-effectiveness analysis (CEA) in schizophrenia spans
      three types of studies-randomized trial-based studies (six), retrospective cohort
      based studies (six) and decision model-based studies (five). Comparing results
      from CEA across all types of studies in schizophrenia reveals a large ambiguity
      in the incremental evaluation of newer atypicals. For treatment-resistant
      patients, clozapine seems to produce cost saving and better outcomes compared to
      standard neuroleptics. However, there is tremendous uncertainty in the estimates
      of cost savings and clinical benefits that may prevent decision makers from
      making optimal policy decisions about insurance coverage and formulary design
      based on these results. For chronic schizophrenic patients, the results are even
      more ambiguous. For example, the studies based on trial settings find risperidone
      to cost more than haloperidol, while studies based on cohort design and decision
      models find risperidone to be either equivalent or lower in costs than
      haloperidol. CONCLUSIONS: Further studies of cost-effectiveness need to be
      carried out with careful consideration of the limitations of published analyses.
      There are a variety of theoretical and methodological issues that are important
      to consider during the development of new decision models in this field.

PMID- 15474917
TI  - Social cognitive bias and neurocognitive deficit in paranoid symptoms: evidence
      for an interaction effect and changes during treatment.
AB  - Persistent paranoid symptoms are best understood as having multiple causal
      mechanisms. An enhanced multidimensional understanding of paranoia may result
      from the convergence of two distinct measurement paradigms, experimental
      psychopathology and social cognitive research. This study investigated the role
      of neurocognitive deficits and emotion misperception bias as they relate to
      paranoid symptoms at two different time points in a sample of individuals with
      severe mental illness (primarily schizophrenia spectrum disorders [N=91])
      undergoing intensive psychosocial rehabilitation. Before intensive rehabilitation
      (but after initial stabilization), paranoid symptoms were related to a tendency
      to misperceive emotion as disgust. The impact of this social cognitive bias was
      amplified by perseveration (as measured by the COGLAB Card Sorting Task).
      Perseverative errors were associated with paranoid symptoms at both time points.
      After 6 months of treatment, there were significant reductions in paranoid
      symptoms and perseverative errors but no significant changes in emotion
      misperception biases. This study is one of few to date to evaluate the
      contribution of both neurocognitive deficits and social cognitive biases to
      paranoid symptoms. The results demonstrate how social cognitive biases can
      interact with neurocognitive deficits in expression of paranoid symptoms, and how
      these relationships change during treatment.

PMID- 15474918
TI  - Thalamus size and outcome in schizophrenia.
AB  - The size of the thalamus was assessed in 106 patients with schizophrenia and 42
      normal controls using high-resolution magnetic resonance imaging. The thalamus
      was traced at five axial levels proportionately spaced from dorsal to ventral
      directions. Patients with schizophrenia had significantly smaller thalamic areas
      at more ventral levels. Thalamic size was positively associated with frontal lobe
      and temporal lobe size. The effects were most marked in the patients with poorer
      clinical outcome (i.e., "Kraepelinian" patients). These findings are consistent
      with post-mortem and MRI measurement suggesting reduction in volume of the
      pulvinar, which occupies a large proportion of the ventral thalamus and which has
      prominent connections to the temporal lobe.

PMID- 15474919
TI  - Paracontrast and metacontrast in schizophrenia: clarifying the mechanism for
      visual masking deficits.
AB  - Schizophrenic patients consistently demonstrate performance deficits on visual
      masking procedures. Visual masking can occur through two distinctly different
      mechanisms: interruption and integration. One highly effective way to limit the
      masking mechanism to interruption is to use a mask that surrounds, but does not
      spatially overlap, the target. These procedures are called paracontrast and
      metacontrast (for forward and backward masking, respectively). Despite their
      clear advantages for interpretation, paracontrast and metacontrast have not been
      used previously in schizophrenia. In the present study, we examined the
      reliability of the paracontrast and metacontrast procedures by administering
      these tasks to 103 schizophrenic patients and 49 normal control subjects. In
      addition, we compared the results to those from a low-energy masking condition,
      which is an alternative way to limit masking to interruption. Patients showed
      deficits on both the paracontrast and metacontrast procedures. The deficits in
      paracontrast and metacontrast were comparable to those seen previously with low
      energy masking. These results suggest that the paracontrast/metacontrast
      procedure and the procedure using a low-energy mask are roughly equally sensitive
      to deficits in early visual processing among schizophrenic patients. These
      results bolster previous conclusions that schizophrenic patients show deficits on
      visual masking tasks even when masking on those tasks occurs entirely through the
      interruption mechanism.

PMID- 15474920
TI  - Impaired emotional learning and reduced amygdala size in schizophrenia: a 3-month
      follow-up.
AB  - Individuals with schizophrenia have difficulties in emotional information
      processing. A relationship between behavioral variables of emotional processing
      and structural amygdala alterations in schizophrenia has been proposed but not
      shown, yet. Morphological studies of amygdala size in schizophrenia have yielded
      inconsistent results. The current study assessed paired associates learning of
      emotional and neutral faces in 16 subjects with schizophrenia during acute
      episode and in relative remission after 3 months. Sixteen matched controls were
      studied for comparison. Subjects also underwent structural magnetic resonance
      imaging (3D-MRI) at the first time of assessment. Subjects with schizophrenia
      showed a significant decrease (by 13%) in total size of the amygdala compared to
      controls, which was more pronounced on the right side. Subjects with
      schizophrenia improved associative learning of facial identities but not of
      emotional facial expressions after relative remission of psychotic symptoms.
      Volume of the right amygdala in subjects with schizophrenia and in controls was
      significantly related to emotional learning, indicating better learning in
      subjects with larger amygdala size. Our results indicate that subjects with
      schizophrenia have a deficit to form associations when emotionally loaded
      material is used. This deficit seems to be trait-like and independent of disease
      state. It seems to be linked to size reduction of the right amygdala in
      schizophrenia.

PMID- 15474921
TI  - Telephone administration of neuropsychological tests can facilitate studies in
      schizophrenia.

PMID- 15474922
TI  - Screening for prodromal adolescents in an isolated high-risk population.

PMID- 15474923
TI  - Functional magnetic resonance imaging examination of the magnocellular visual
      pathway in nonpsychotic relatives of persons with schizophrenia.

PMID- 15474924
TI  - Quetiapine treatment in early psychosis: no evidence of cataracts.

PMID- 15474925
TI  - Instability of cognitive processing systems in schizophrenia.

PMID- 15474926
TI  - Stable deficits in gray matter volumes following a first episode of
      schizophrenia.

PMID- 15474927
TI  - Ethanol-diesel fuel blends -- a review.
AB  - Ethanol is an attractive alternative fuel because it is a renewable bio-based
      resource and it is oxygenated, thereby providing the potential to reduce
      particulate emissions in compression-ignition engines. In this review the
      properties and specifications of ethanol blended with diesel fuel are discussed.
      Special emphasis is placed on the factors critical to the potential commercial
      use of these blends. These factors include blend properties such as stability,
      viscosity and lubricity, safety and materials compatibility. The effect of the
      fuel on engine performance, durability and emissions is also considered. The
      formulation of additives to correct certain key properties and maintain blend
      stability is suggested as a critical factor in ensuring fuel compatibility with
      engines. However, maintaining vehicle safety with these blends may entail fuel
      tank modifications. Further work is required in specifying acceptable fuel
      characteristics, confirming the long-term effects on engine durability, and
      ensuring safety in handling and storing ethanol-diesel blends.

PMID- 15474928
TI  - Effect of cysteine on methionine production by a regulatory mutant of
      Corynebacterium lilium.
AB  - The production of methionine by submerged fermentation using a mutant strain of
      Corynebacterium lilium was studied to determine suitable conditions for obtaining
      high productivity. The mutant strain resistant to the methionine analogues
      ethionine, norleucine, methionine sulfoxide and methionine methylsulfonium
      chloride produced 2.34 g l(-1) of methionine in minimal medium containing glucose
      as carbon source. The effect of cysteine on methionine production in a 15 l
      bioreactor was studied by supplementing cysteine intermittently during the course
      of fermentation. The addition of cysteine (0.75 g l(-1)h(-1)) every 2 h to the
      production medium increased the production of methionine to 3.39 g l(-1). A
      metabolic flux analysis showed that during cysteine supplementation the ATP
      consumption reduced by 20%. It also showed that the increase in flux from
      phosphoenol pyruvate to oxaloacetate leads to higher methionine production.
      Results indicate that controlling the respiratory quotient close to 0.75 will
      produce the highest amount of methionine and that regulatory mutants also
      resistant to analogues of cysteine would be better methionine over producers.

PMID- 15474929
TI  - Agars from three species of Gracilaria (Rhodophyta) from Yucatan Peninsula.
AB  - Gracilaria cervicornis, Gracilaria blodgettii and Gracilaria crassissima growing
      along the coasts of Yucatan were investigated for their agar content. The effect
      of different concentrations of NaOH in the alkali treatment was evaluated. The
      three species of Gracilaria produced agars, both native and alkali treated, with
      different properties confirming the heterogeneity of the agar polymers in this
      genera. G. cervicornis produces agar polymers with an occurrence of methoxylation
      and sulphation at the C-6 of the beta-D-galactose residues, and with an extra
      methylation due to the presence of the 4-O-methyl-alpha-L-galactose residue. The
      presences of these residues is responsible for the extremely poor gelling ability
      of its agarocolloids, whose commercial value seems to be quite low. Agar extracts
      from G. blodgettii showed the typical pattern of unsubstituted agar with a very
      low degree of methylation on both galactose residues. The discrepancy found
      between sulphate content and NMR data of agar from this species requires a more
      detailed structural investigation. G. crassissima produces a good quality agar
      after sulphate precursor sequences have been removed by alkaline treatment, and
      it may be considered for exploitation as a source of commercial grade agar.
      Alkali treatment was effective both in removing alkali-labile sulphate and
      increasing the gel strength in G. crassissima but not in G. cervicornis and G.
      blodgettii.

PMID- 15474930
TI  - Use of coagulants in treatment of olive oil wastewater model solutions by induced
      air flotation.
AB  - Natural polyelectrolytes are suitable coagulants for the treatment of industrial
      and minicipal wastewaters because they are safe and have environmental benefits.
      Chitosan, a natural cationic polyelectrolyte, and other similar coagulants were
      used in the treatment of an olive oil water suspension as a model for the
      processing wastewater. The effect of chitosan, starch, alum and ferric chloride
      on the coagulation of oil droplets were determined by the jar test apparatus and
      turbidometric measurements. Olive oil emulsion samples were prepared by the use
      of surface active agents and other agents that could form stable oil water
      emulsions. The effect of parameters such as pH, ionic strength and optimum dosage
      of the coagulants were determined in the jar test experiments. Following the jar
      experiments, with the optimum concentration of the suitable coagulant, the
      emulsions were placed in an induced air flotation (IAF) cell to separate the
      coagulated oil droplets from solution. In the air flotation experiments, the
      effect of temperature, surfactant concentration and air flowrate were determined
      on the decrease of turbidity and COD of the emulsion samples. In the jar
      experiments, chitosan and alum used together at concentrations of 15 and 25 ppm,
      respectively, at pH 6 produced the lowest turbidity values. In the air flotation
      experiments, a concentration of 100 ppm of chitosan, an air flowrate of 3 l/min,
      aeration time of 45 s, temperature of 20 degrees C and pH 6 produced optimum
      levels. At optimum conditions of coagulation and flotation stages, the COD of the
      olive oil emulsion could be reduced by 95%.

PMID- 15474931
TI  - Use of low-cost biological wastes and vermiculite for removal of chromium from
      tannery effluent.
AB  - Biological wastes (sawdust, rice husk, coirpith and charcoal) and a naturally
      occurring mineral (vermiculite) have been tested for their effectiveness in
      removing Cr from tannery effluent through batch and column experiments. The
      adsorption capacities of the substrates were also evaluated using isotherm tests
      and computing distribution co-efficient. The sawdust exhibited a higher
      adsorption capacity (k = 1482 mgkg(-1)), followed by coirpith (k = 159 mgkg(-1)).
      The biosorbent and mineral vermiculite in columns were found very effective in
      removing Cr from tannery effluent. About 94% removal of Cr was achieved by a
      column of coirpith, and equally (93%) by a column containing a mixture of
      coirpith and vermiculite. This study showed that biological wastes are potential
      adsorbents of Cr, which could be successfully used to reduce the Cr
      concentrations in tannery effluent.

PMID- 15474932
TI  - Use of Yarrowia lipolytica strains for the treatment of olive mill wastewater.
AB  - The principal aim of this research was to evaluate the ability of different
      Yarrowia lipolytica strains, having different origin, to grow in olive mill
      wastewater (OMW) and reduce its COD level. All the strains were able to grow in
      undiluted OMW; the comparison between the data obtained in a semi-synthetic
      medium and in OMW suggests that lipases with different specificity can be
      produced in relation to the medium composition. Under the adopted conditions, the
      reduction of the OMW COD values varied from 1.47% and 41.22% of the initial
      value. Some strains determined a significant reduction of polyphenol content,
      while other ones caused its apparent increase. Moreover, some Y. lipolytica
      strains, isolated from chilled foods, produced the highest citric acid
      concentrations. These results evidenced that some Y. lipolytica strains are good
      candidates for the reduction of the pollution potential of OMW and for the
      production of enzymes and metabolites such as lipase and citric acid.

PMID- 15474933
TI  - Nitrogen availability of anaerobic swine lagoon sludge: sludge source effects.
AB  - Increased numbers of swine producers will be removing sludge from their anaerobic
      waste treatment lagoons in the next few years, due to sludge exceeding designed
      storage capacity. Information on availability of nitrogen (N) in the sludge is
      needed to improve application recommendations for crops. The objective of this
      study was to investigate possible effects of different companies and types of
      swine operations on the availability of N in sludge from their associated
      lagoons. A laboratory incubation study was conducted to quantify the availability
      of N (i.e. initial inorganic N plus the potentially mineralizable organic N) in
      the sludge. Nine sludge sources from lagoons of sow, nursery and finishing
      operations of three different swine companies were mixed with a loamy sand soil
      (200 mg total Kjeldahl N kg(-1) soil) and incubated at a water content of 0.19 g.
      water g(-1) dry soil and 25+/-2 degrees C for 12 weeks. Samples were taken at
      eight times over the 12-week period and analyzed for inorganic N (i.e. NH(4)-N
      and NO(3)-N) to determine mineralization of organic N in the sludge. Company and
      type of swine operation had no significant effects (P < 0.05) on the pattern of
      inorganic N accumulation over time. Thus, inorganic N accumulation from all
      sludge sources was fit to a first order equation [Nt = Ni + No (1-e(-kt)]. This
      relationship indicated that of the 200 mg of total sludge N added per kg soil,
      23.5% was in the form of potentially mineralizable organic N (No) and 17.5% was
      in the form of inorganic N (Ni). The sum of these two pools (41%) represents an
      estimate of the proportion of total N in the applied sludge in plant available
      form after the 12 week incubation. While plant N availability coefficients were
      not measured in this study, the lack of significant company or type of swine
      operation effects on sludge N mineralization suggests that use of the same plant
      N availability coefficient for sludge from different types of lagoons is
      justifiable. The validity of this interpretation depends on the assumption that
      variation in other components of different sludge sources such as Cu and Zn does
      not differentially alter N uptake by the receiver crops.

PMID- 15474934
TI  - Oil removal from used sorbents using a biosurfactant.
AB  - Oil spills impose serious damage on the environment. Mechanical recovery by the
      help of oil sorbents is one of the most important countermeasures in oil spill
      response. Most sorbents, however, end up in landfills or in incineration after a
      single use. These options either produce another source of pollution or increase
      the oil recovery cost. In this study a biosurfactant was used to clean used oil
      sorbents. This use of biosurfactants is new. Washing parameters tested included
      sorbent type, washing time, surfactant dosage and temperature. It was found that
      with biosurfactant washing more than 95% removal of the oil from sorbents was
      achieved, depending on the washing conditions. Biosurfactants were found to have
      considerable potential for recycling the used sorbents.

PMID- 15474935
TI  - Effect of organic loading rate on the stability, operational parameters and
      performance of a secondary upflow anaerobic sludge bed reactor treating piggery
      waste.
AB  - A study of anaerobic digestion of piggery wastewater was carried out in a
      laboratory-scale sludge bed reactor as a secondary treatment. The effect of
      organic volumetric loading rates (BV) in the range of 1.0-8.1 g TCOD/ld on the
      process performance was evaluated. The best results were obtained at BV equal to
      or lower than 4 g TCOD/ld. At higher BV values, the removal efficiency of the
      process decreased suddenly. A linear relationship was found between the effluent
      SCOD and the TVFA/alkalinity ratio (P). A relationship was found among the
      different operational variables (BV , removal efficiency, effluent soluble COD,
      soluble COD removal rate (R), retention factor (phi), specific microbial growth
      rate (mu), methane production rate per volume of reactor and per volume of waste
      treated--QM and qM, respectively) and the corresponding regression equations were
      obtained. An increase of BV determined a decrease of removal efficiency, phi and
      qM and an increase of effluent soluble COD, mu, R and QM. The value of the
      maximum specific microbial growth rate (muM) determined through the equation that
      correlated BV and mu was found to be 0.19 d(-1). This value was of the same
      magnitude as those reported in other works of anaerobic digestion of piggery
      waste.

PMID- 15474936
TI  - Effects of farmyard manure and fertilizers on yield, fibre quality and nutrient
      balance of rainfed cotton (Gossypium hirsutum).
AB  - Two-year field experiments were conducted to evaluate the effect of fertilizer
      with or without farmyard manure (FYM) application on cotton productivity and
      fibre quality. A partial nutrient balance was calculated by the difference method
      (nutrient applied--crop removal). Seed cotton yield was improved with addition of
      FYM (5 Mg ha(-1)). Application of both N and P resulted in significant
      improvements in seed cotton yield than the control and without N plots (PK).
      Uniformity ratio and ginning outturn (GOT) was greater in the FYM amended plots
      than the plots without FYM. Nitrogen and P balance was positive in the fertilizer
      N and P applied plots whereas K balance was negative in spite of the addition of
      fertilizer-K. Potassium balance was positive only when FYM was applied. These
      studies suggest that it is advantageous to apply FYM as it improves fibre yield
      by way of improved GOT and maintains a positive nutrient balance.

PMID- 15474937
TI  - Piggery wastewater characterisation for biological nitrogen removal process
      design.
AB  - In intensive farming areas, the design of biological nitrogen removal plants for
      piggery wastewater requires the determination of the chemical oxygen demand (COD)
      fractions of the effluent. For this purpose, an experimental procedure was
      developed to quantify the inert soluble (SI) and particulate (XI) COD fractions,
      as well as the readily (SS) and the slowly (XS) biodegradable COD fractions. For
      the four wastewaters tested, the SI and the XI fractions were equal to 3-4 g
      O(2)l(-1) and 17-28 g O(2)l(-1), respectively, which resulted in a total inert
      fraction of 42-84% of total COD. The SS and the XS fractions were very variable,
      ranging 0-5 g O(2)l(-1) and 4-25 g O(2)l(-1) respectively, depending on the farm
      management practices and the storage conditions prior to biological treatment.
      From these results, the denitrification potential of the piggery wastewaters for
      biological nitrogen removal treatment could be assessed.

PMID- 15474938
TI  - Nitrogen removal and recycling by Scenedesmus obliquus in semicontinuous cultures
      using artificial wastewater and a simulated light and temperature cycle.
AB  - Semicontinuous cultures of Scenedesmus obliquus in artificial wastewater were
      maintained with 30% and 40% daily dilutions and under a 14:10 h light-dark cycle,
      with temperatures of 25.5 and 17 degrees C during light and dark hours. Under
      this regime, the production of organic biomass was 39.3 and 25.2 mg l(-1)d(-1)
      for the 30% and 40% dilutions, and 24.9 and 16.7 mg l(-1)d(-1) of single-cell
      proteins. Most of the nitrogen removal took place during the light hours, with
      daily totals of 9.27 and 8.45 mg l(-1) for the 30% and 40% dilutions. With the
      former, 43.7% of the nitrogen removed was recycled by the microalgae into
      proteins and other organic nitrogen cell contents, but this efficiency decreased
      to 26.4% when the dilutions were raised to 40%.

PMID- 15474939
TI  - Isolation of colour components from native dye-bearing plants in northeastern
      India.
AB  - Recently dyes derived from natural sources have emerged as important alternatives
      to synthetic dyes. A study was initiated in the year 2000 at the RRL (CSIR),
      Jorhat to extract dyes from parts of five different plant species indigenous to
      northeastern India. The colour components responsible for dyeing were isolated
      and their chemical constituents were established based on chemical and
      spectroscopic investigations. The principal colour components from the species
      Morinda angustifolia Roxb., Rubia cordifolia Linn. and Tectona grandis Linn. were
      found to contain mainly anthraquinone moieties in their molecules. Those from the
      species Mimusops elengi Linn. and Terminalia arjuna (Roxb.) Wight & Arn.
      contained flavonoid moieties in their molecules. The absorption of dye (%) on
      fibres increased with increasing concentrations of dye in the dye-bath. Maximum
      absorption of dyes on fibres was obtained at 3% concentration of dyes obtained
      from R. cordfolia (35.350%), M. angustifolia (31.580%) and T. grandis (25.888%)
      and at 4% concentration of the dyes from M. elengi (31.917%) and T. arjuna
      (12.246%). The K/S values were found to increase with the increase in
      concentration of mordants. The colour co-ordinates of dyed samples were found to
      lie in the yellow-red quadrant of the colour space diagram. The dyes obtained
      from the native plants may be alternative sources to synthetic dyes for the
      dyeing of natural silk and cotton.

PMID- 15474940
TI  - Analysis and enhancement of astaxanthin accumulation in Haematococcus pluvialis.
AB  - The green microalga Haematococcus pluvialis was cultured with different
      concentrations of NaNO(3) to determine the effect on cell growth and astaxanthin
      accumulation. The optimum nitrate concentration to obtain astaxanthin and to
      avoid the cessation of cell division was 0.15 g/l NaNO(3). The ratio chlorophyll
      a/total carotenoids proved a good physiological indicator of nitrogen deficiency
      in the cell. The effect of different carbon sources, malonate and acetate, on
      astaxanthin accumulation was also studied; up to 13 times more carotenoids per
      cell were accumulated in cultures with malonate than in cultures without this
      compound. The pigment analysis was performed by a new low toxicity HPLC method
      capable of separating chlorophylls a and b, carotenes and xanthophylls in a short
      period of time, using low volumes of solvents and with an economical price. With
      this method even echinenone was separated, which had been unsuccessful by any
      other method.

PMID- 15474941
TI  - Polysaccharides from the red seaweed Gracilaria dura (Gracilariales, Rhodophyta).
AB  - The yield and physical and chemical properties of agars from Gracilaria dura (C.
      Agardh) J. Agardh, harvested in Thau lagoon (Mediterranean sea, France), were
      investigated. The agar yield ranged from 32% to 35%. Gel strength of agar ranged
      from 263 to 600 g cm(-2), with the maximum observed in October. A positive
      correlation was found between agar yield and gel strength (r = 0.82; P < 0.01).
      The gelling temperature followed the same pattern of gel strength and also showed
      higher value in October (43 degrees C). The nitrogen content varied from 1.04+/
      0.60% (June) to 4.70+/-0.01% (October). A positive correlation was noted between
      nitrogen content and gel strength (r = 0.77; P < 0.05). The 3,6-anhydrogalactose
      content ranged from 0.70 to 0.84 and showed monthly significant differences (P <
      0.05). There was a positive correlation between 3,6-anhydrogalactose content and
      gel strength. The values of sulfate content were relatively constant during the
      studied period and no significant differences were observed. The relative high
      gel strength indicates that this species may be considered as source of agar for
      commercial use.

PMID- 15474942
TI  - Fishery by-product as a nutrient source for bacteria and archaea growth media.
AB  - A highly soluble fish protein hydrolysates (FPH) with an 80% protein (peptide
      size between 1.5 and 20 kDa) and a low free amino acid content was obtained from
      hake (Merluccius hubssi) filleting waste [Lat. Am. Appl. Res. 30 (2000) 241].
      Assays with Halobacterium salinarum, Escherichia coli, Bacillus subtilis and
      Staphylococcus epidermidis were performed in order to test that FPH as nutrient
      source for archaea and eubacteria culture media. Cell growth was evaluated by
      plate count, and by monitoring turbidity and nucleic acids content in liquid
      cultures. Neither cell growth nor generation times resulting from control and FPH
      cultures exhibited statistically significant differences at alpha: 0.05
      suggesting that FPH can be used as an alternative substrate for microorganism
      cultural purposes.

PMID- 15474943
TI  - Removal of copper, chromium, and arsenic from CCA-treated wood onto chitin and
      chitosan.
AB  - Chitin and chitosan are naturally abundant biopolymers which are of interest to
      research concerning the sorption of metal ions since the amine and hydroxyl
      groups on their chemical structures act as chelation sites for metal ions. This
      study evaluates the removal of copper, chromium, and arsenic elements from
      chromated copper arsenate (CCA)-treated wood via biosorption by chitin and
      chitosan. Exposing CCA-treated sawdust to various amounts of chitin and chitosan
      for 1, 5, and 10 days enhanced removal of CCA components compared to remediation
      by deionized water only. Remediation with a solution containing 2.5 g chitin for
      10 days removed 74% copper, 62% chromium, and 63% arsenic from treated sawdust.
      Remediation of treated sawdust samples using the same amount of chitosan as
      chitin resulted in 57% copper, 43% chromium, and 30% arsenic removal. The results
      suggest that chitin and chitosan have a potential to remove copper element from
      CCA-treated wood. Thus, these more abundant natural amino polysaccharides could
      be important in the remediation of waste wood treated with the newest
      formulations of organometallic copper compounds and other water-borne wood
      preservatives containing copper.

PMID- 15474945
TI  - Ultrasonic effects on electroorganic processes. Part 25. Stereoselectivity
      control in cathodic debromination of stilbenedibromides.
AB  - Ultrasonic effects on the cathodic debromination of stilbenedibromides on a
      platinum cathode was examined. Current efficiency and stereoselectivity for trans
      stilbene, which was formed along with cis-stilbene in the cathodic debromination
      of stilbenedibromides, were significantly increased under ultrasonication with an
      intensity over the ultrasonic cavitation threshold. This ultrasonic effect is
      rationalized as due to mass transport promotion in the electrode-electrolytic
      solution interface. A mechanism for the ultrasonic effect is discussed in detail
      on the basis of the reaction pathway of the debromination of stilbenedibromides.

PMID- 15474946
TI  - Electrochemical study of silver thiosulphate reduction in the absence and
      presence of ultrasound.
AB  - The electrochemical reduction of silver thiosulphate was studied
      potentiostatically on platinum electrodes in the absence and presence of
      ultrasound (20 kHz). This system is irreversible and the reaction is both
      diffusion and kinetically controlled. The slowest step is the kinetic reaction
      especially the chemisorption of ions at the electrode surface. Ultrasound greatly
      improves the mass transport, which can be explained by changing from diffusion to
      mainly convection. This paper reports the effect of ultrasound upon electrode
      kinetic and mass-transport parameters at various RDE rotation speeds and
      ultrasonic intensities. It was found that the heterogeneous rate constant (kf) is
      improved in the presence of ultrasound due to the increase in the formal or
      standard heterogeneous rate constant (k0) (approximately by 10-fold under
      sonication).

PMID- 15474947
TI  - Effects of ultrasonic irradiation on the properties of coatings obtained by
      electroless plating and electro plating.
AB  - This paper deals with the effects of ultrasonic irradiation on electroless copper
      coating i.e. metallic deposition on non-conductive substrates and on
      electroplating on metallic substrates. Ultrasonic irradiation was both applied
      during activation (surface preparation for the electroless coating) and during
      plating steps in both cases. Several parameters were monitored, such as plating
      rates, practical adhesion, hardness, internal stress versus varying acoustic
      powers and frequencies. Optimum conditions for irradiation time, frequency and
      power were determined for each step. It appears clearly that ultrasound use
      affects deposit properties. Then, changes in the coating mechanisms can be
      discussed, and several parameters will be explored in this paper, to explain
      enhancement of deposit properties: increase in catalyst specific area, stirring
      dependence, surface energy evolution, dihydrogen desorption, structure of
      coating.

PMID- 15474948
TI  - A review and assessment of hydrodynamic cavitation as a technology for the
      future.
AB  - In the present work, the current status of the hydrodynamic cavitation reactors
      has been reviewed discussing the bubble dynamics analysis, optimum design
      considerations, design correlations for cavitational intensity (in terms of
      collapse pressure)/cavitational yield and different successful chemical synthesis
      applications clearly illustrating the utility of these types of reactors. The
      theoretical discussion based on the modeling of the bubble dynamics equations
      aims at understanding the design information related to the dependency of the
      cavitational intensity on the operating parameters and recommendations have been
      made for the choice of the optimized conditions of operating parameters. The
      design information based on the theoretical analysis has also been supported with
      some experimental illustrations concentrating on the chemical synthesis
      applications. Assessment of the hydrodynamic cavitation reactors and comparison
      with the sonochemical reactors has been done by citing the different industrially
      important reactions (oxidation of toluene, o-xylene, m-xylene, p-xylene,
      mesitylene, o-nitrotoluene, p-nitrotoluene, m-nitrotoluene, o-chlorotoluene and p
      chlorotoulene, and trans-esterification reaction i.e., synthesis of bio-diesel).
      Some recommendations have also been made for the future work to be carried out as
      well as the choice of the operating conditions for realizing the dream of
      industrial scale applications of the cavitational reactors.

PMID- 15474949
TI  - The optimisation of ultrasonic cleaning procedures for dairy fouled
      ultrafiltration membranes.
AB  - Ultrafiltration (UF) of whey is a major membrane based process in the dairy
      industry. However, commercialization of this application has been limited by
      membrane fouling, which has a detrimental influence on the permeation rate. There
      are a number of different chemical and physical cleaning methods currently used
      for cleaning a fouled membrane. It has been suggested that the cleaning frequency
      and the severity of such cleaning procedures control the membrane lifetime. The
      development of an optimal cleaning strategy should therefore have a direct
      implication on the process economics. Recently, the use of ultrasound has
      attracted considerable interest as an alternative approach to the conventional
      methods. In the present study, we have studied the ultrasonic cleaning of
      polysulfone ultrafiltration membranes fouled with dairy whey solutions. The
      effects of a number of cleaning process parameters have been examined in the
      presence of ultrasound and results compared with the conventional operation.
      Experiments were conducted using a small single sheet membrane unit that was
      immersed totally within an ultrasonic bath. Results show that ultrasonic cleaning
      improves the cleaning efficiency under all experimental conditions. The
      ultrasonic effect is more significant in the absence of surfactant, but is less
      influenced by temperature and transmembrane pressure. Our results suggest that
      the ultrasonic energy acts primarily by increasing the turbulence within the
      cleaning solution.

PMID- 15474950
TI  - Analysis of concentration characteristics in ultrasonic atomization by droplet
      diameter distribution.
AB  - The droplet diameter distribution and concentration characteristics in ultrasonic
      atomization were experimentally studied. The samples were aqueous solutions of
      methanol, ethanol and 1-propanol. The diameter distribution of atomized droplets
      showed the normal distribution, and the median diameter and standard deviation
      were expressed by means of the ultrasonic condition and the liquid properties.
      The concentration characteristic in ultrasonic atomization was analyzed by using
      the model of shell and core to the atomized droplet, where the former and latter
      consist of solute and solution, respectively. The value, which was surface solute
      amount in droplet multiplied by the molecular volume, increased with increasing
      solute molar fraction in bulk liquid and was independent of alcohol kinds. The
      rate of accompanying liquid and the solute molar fraction in accompanied liquid
      were estimated from the diameter distribution and the surface solute amount in
      droplet.

PMID- 15474951
TI  - Dependence of the characteristics of bubbles on types of sonochemical reactors.
AB  - Computer simulations of bubble oscillations in liquid water irradiated by an
      ultrasonic wave have revealed that the characteristic of bubbles depends on types
      of sonochemical reactors: a horn-type reactor and a standing-wave type reactor.
      When the acoustic amplitude is large at 20 kHz, the bubble content is mostly
      water vapor even at the end of the bubble collapse and the temperature inside a
      bubble at the collapse is relatively low. On the other hand, when the acoustic
      amplitude is relatively low, the bubble content is mostly noncondensable gas at
      the end of the bubble collapse and the bubble temperature is relatively high. In
      a horn-type sonochemical reactor, the former type of bubbles are dominant because
      many bubbles exist near the horn-tip where the acoustic amplitude is large, while
      in a standing-wave type reactor the latter type of bubbles are dominant because
      the Bjerknes force gathers bubbles at a region where acoustic amplitude is
      relatively low.

PMID- 15474952
TI  - Model-based optimization of ultrasonic transducers.
AB  - Numerical simulation and automated optimization of Langevin-type ultrasonic
      transducers are investigated. These kind of transducers are standard components
      in various applications of high-power ultrasonics such as ultrasonic cleaning and
      chemical processing. Vibration of the transducer is simulated numerically by
      standard finite element method and the dimensions and shape parameters of a
      transducer are optimized with respect to different criteria. The novelty value of
      this work is the combination of the simulation model and the optimization problem
      by efficient automatic differentiation techniques. The capabilities of this
      approach are demonstrated with practical test cases in which various aspects of
      the operation of a transducer are improved.

PMID- 15474953
TI  - Characterization of a 20 kHz sonoreactor. Part I: analysis of mechanical effects
      by classical and numerical methods.
AB  - Numerical simulations have been carried out in order to characterize the
      ultrasonic field propagation and to obtain the spatial distribution of the
      mechanical effect derived from it. The results have been compared with those
      obtained with different classical physical methods (calorimetry, aluminium foil
      erosion, thermal probes) and have given useful information about the influence of
      the presence of probes and auxiliary tools in the ultrasonic field. All these
      information have been used for the development of the Part II of this work:
      analysis of chemical effects, providing an accurate picture of the reaction
      environment in the sonoreactor used (20 kHz, 100 W supplied by Undatim) for
      further uses in sonoelectrochemical studies.

PMID- 15474954
TI  - Characterization of a 20 kHz sonoreactor. Part II: analysis of chemical effects
      by classical and electrochemical methods.
AB  - A new electrochemical redox probe has been investigated in order to characterize
      the local production of radicals during the cavitation events. The results have
      been compared with those obtained with Fe(CN)6(3-)/Fe(CN)6(4-) (electrochemical
      probe for local mechanical effects) and classical chemical methods such as iodide
      and Fricke dosimeters (chemical probes for global effects).

PMID- 15474955
TI  - Spatial study on a multibubble system for sonochemistry by laser-light
      scattering.
AB  - Volumetric oscillation of multiple cavitation bubbles in an ultrasonic standing
      wave field is investigated spatially through the intensity measurements of
      scattered light from bubbles changing the measuring position in the direction of
      sound propagation. When a thin light sheet finer than half of wavelength of sound
      is introduced into the cavitation bubbles, at an antinode of sound pressure the
      scattered light intensity oscillates. The peak-to-peak light intensity
      corresponds to the number of the bubbles which contribute to the sonochemical
      reaction because the radius for oscillating bubbles at pressure antinodes is
      restrictive in a certain range due to the shape instability and the action of
      Bjerknes force that expels from the antinode bubbles that are larger than the
      resonant size. The experimental results show that the intensity waveform of
      oscillating scattered light measured at the side near the sound source is similar
      to the waveform as seen in a single-bubble experiment. The peak-to-peak light
      intensity for the scattered light waveform is low at the side near the sound
      source where the progressive wave is dominant, while at the side near the water
      surface far from the sound source the intensity is relatively high and has
      periodic structure corresponding to the periodicity of half wavelength from the
      standing wave. These tendencies of high intensity near the water surface and the
      periodicity correspond to the periodic luminescent stripes seen in images of
      luminescence in an ultrasonic standing wave as reported by Hatanaka et al. [Jpn.
      J. Appl. Phys. 39 (2000) 2962]. The present method of light scattering is
      promising for evaluating spatial distribution of violently oscillating cavitation
      bubbles which effect sonochemical reactions.

PMID- 15474956
TI  - Experimental and theoretical investigation of the mean acoustic pressure in the
      cavitation field.
AB  - The cavitation field radiated by a 20 kHz sonotrode-type transducer is
      experimentally and theoretically analyzed. Special interest is paid to the origin
      of the strong fluid streaming appearing in low frequency sonoreactors. A new
      experimental procedure is proposed to evaluate the mean acoustic pressure inside
      the fluid. This parameter has been quantified for different points and
      amplitudes. The velocity of the radiating surface is controlled by a laser
      interferometer and is always sinusoidal. Train wave excitation is used. The
      pressure wave and amplitude are measured in the tank with a calibrated
      hydrophone. The acoustic mean pressure is estimated from the total pressure value
      at the end of the pulse after an adequate filtering. An analytical nonlinear
      second order model based on the coupling of the equations of the fluid mechanics
      with the Rayleigh-Plesset equation is developed in order to relate the measured
      acoustic parameters to the cavitation state of the fluid. The distributions of
      the fundamental amplitude and mean pressure are calculated as a function of
      bubble density and bubble size. A qualitative theoretical description of the
      experimental data is presented. Quantitative differences and model limitations
      are commented.

PMID- 15474957
TI  - Oxidation of alkylarenes using aqueous potassium permanganate under cavitation:
      comparison of acoustic and hydrodynamic techniques.
AB  - Various alkylarenes were oxidized to the corresponding aryl carboxylic acids
      using aqueous potassium permanganate under heterogeneous condition in the
      presence of hydrodynamic cavitation and the results of the reaction have been
      compared with the acoustic cavitation in terms of their energy efficiency. The
      rate of reaction was determined for each reaction. In the oxidation of p-xylene,
      seven times more product could be obtained in the case of hydrodynamic cavitation
      than in the case of acoustic cavitation. The reaction was found to be
      considerably accelerated at ambient temperature.

PMID- 15474958
TI  - The Suzuki homocoupling reaction under high-intensity ultrasound.
AB  - The Pd-catalysed Suzuki homocoupling of boronic acids was successfully carried
      out in water under high-intensity ultrasound (HIU). Heterogeneous catalysis with
      Pd/C, facilitating work up and purification, could be used without adding
      phosphine ligands. Reaction rates and yields were strongly influenced by the
      oxidant employed; excellent results were obtained using either molecular oxygen
      or 3-bromo-4-hydroxycoumarin. 3-Arylation of the latter with the Suzuki procedure
      had failed, exclusively affording the homocoupling products, symmetric biaryls.
      Besides offering a number of operational advantages, the use of HIU broadens the
      field of application for the Suzuki reaction.

PMID- 15474959
TI  - Chemical modification of chitosan under high-intensity ultrasound.
AB  - Chitosan (CTS), a biocompatible, biodegradable, non-toxic polymer, dissolves in
      water only if pH is lowered under 6.5, when a substantial fraction of the amino
      groups is protonated. Its range of application has been much extended by
      partially depolymerising it or converting it to water-soluble derivatives.
      Working under high-intensity ultrasound at 17.8-18.5 kHz, using either a simple
      horn or a cup horn, we achieved a controlled depolymerization of CTS, also
      prepared in high yields several derivatives that can be useful intermediates for
      further chemical modification, as well as several water-soluble derivatives that
      lend themselves to a host of industrial applications. Compared to conventional
      methods, all these reactions went to completion in considerably shorter times at
      lower temperatures.

PMID- 15474960
TI  - Ultrasound effect on Suzuki reactions. 1. Synthesis of unsymmetrical biaryls.
AB  - Ultrasound effect on the Pd(0) catalysed reaction of arylboronic acid with
      halobenzenes was investigated. The effect of catalyst, base as well as solvent
      was tested. Heterogenous reaction of iodoarenes with different arylboronic acids,
      catalysed by Pd/C and KF as the base in methanol:water mixture resulted in good
      yields of cross-coupling products. Reaction time of sonochemical reaction was 1
      h, while 4 h of reflux was necessary to achieve comparable results. Bromobenzenes
      gave best results using aqueous solution of PdCl2 as the catalyst, potassium
      carbonate as the base in toluene:water two phase system using TEBA
      (benzyltriethylammonium chloride) as PT catalyst. Chlorobenzenes gave just feeble
      yields of cross-coupling products.

PMID- 15474961
TI  - Ultrasound supported catalysis.
AB  - An overview on the application of ultrasound in several chemical reactions is
      given. Ultrasound is used in the preparation of catalysts for various reactions,
      i.e. dehydration reactions. The beneficial effect of ultrasound results in clean
      reactions and short reaction times. Criteria for scale-up are also discussed.

PMID- 15474962
TI  - Dehydration reaction of hydroxenin monoacetate in carbon tetrachloride and an
      aliphatic alcohol under ultrasound irradiation.
AB  - A new method for the preparation of an E/Z mixture of vitamin A acetate from
      hydroxenin monoacetate is described. This two-step reaction was studied by
      changing the reaction parameters (reaction temperature, ultrasound power, and
      reaction time) and the alcohol used. This approach consists of the dehydration
      reaction of hydroxenin monoacetate under ultrasound irradiation in CCl4 and an
      aliphatic alcohol under an inert atmosphere. The formation of small amounts of
      HCl from CCl4 and an aliphatic alcohol under ultrasound irradiation is followed
      by the dehydration reaction of hydroxenin monoacetate. An E/Z mixture of vitamin
      A acetate was obtained resulting in the desired pentaenes. Some ethers
      derivatives were also formed as by-products, isolated and characterized. Study of
      the reaction mechanism is also reported here.

PMID- 15474963
TI  - Ultrasound assisted method to increase soluble chemical oxygen demand (SCOD) of
      sewage sludge for digestion.
AB  - The aim of this study was to clarify the possibilities to increase the amount of
      soluble chemical oxygen demand (SCOD) and methane production of sludge using
      ultrasound technologies with and without oxidising agents. The study was done
      using multivariate data analyses. The most important factors affected were
      discovered. Ultrasonically assisted disintegration increased clearly the amount
      of SCOD of sludge. Also more methane was produced from treated sludge in
      anaerobic batch assays compared to the sludge with no ultrasonic treatment.
      Multivariate data analysis showed that ultrasonic power, dry solid content of
      sludge (DS), sludge temperature and ultrasonic treatment time have the most
      significant effect on the disintegration. It was also observed that in the
      reactor studied energy efficiency with high ultrasound power together with short
      treatment time was higher than with low ultrasound power with long treatment
      time. When oxidising agents were used together with ultrasound no increase in
      SCOD was achieved compared the ultrasonic treatment alone and only a slight
      increase in total organic carbon of sludge was observed. However, no enhancement
      in methane production was observed when using oxidising agents together with
      ultrasound compared the ultrasonic treatment alone. Ultrasound propagation is an
      important factor in ultrasonic reactor scale up. Ultrasound efficiency rose
      linearly with input power in sludge at small distances from the transducer.
      Instead, ultrasound efficiency started even to decrease with input power at long
      distances from the transducer.

PMID- 15474964
TI  - Ultrasonic dehalogenation and toxicity reduction of trichlorophenol.
AB  - The study focussed on the effect of ultrasonic frequency and co-pollutants on
      dechlorination and toxicity reduction of a toxic model pollutant, i.e. 2,3,5
      trichlorophenol (TCP). The effect of ultrasonic frequency on TCP degradation and
      chloride formation was studied at 41, 206, 360, 618, 1068, and 3217 kHz. Most
      efficient ultrasonic dechlorination was achieved at 360 kHz. The degradation of
      TCP and adsorbable organic halogens followed pseudo-first-order rate kinetics.
      Toxicity in the bioluminescence test increased during the initial sonication
      period, indicating the temporary formation of more toxic reaction products.
      Subsequently, toxicity was significantly reduced. Dehalogenation efficiency
      decreased in the presence of the hydrophobic radical scavenger t-butanol, whereas
      hydrophilic co-pollutants such as acetate or glucose did not interfere with
      ultrasonic dechlorination and toxicity reduction. After ultrasonic pre-treatment,
      a fast biodegradation of the remaining organic pollutants was observed. In
      conclusion, the results demonstrate the potential of integrated
      ultrasonic/biological approaches for the treatment of wastewaters containing
      toxic pollutants.

PMID- 15474965
TI  - Sonochemical reaction of selected cyclic C6Hx hydrocarbons in organic solvents.
AB  - The rates and products of the sonochemical reactions of benzene, 1,4
      cyclohexadiene, 1,3-cyclohexadiene, cyclohexene, and cyclohexane in selected
      organic solvents have been investigated. The sonochemical reactions of these
      educts in the investigated organic solvents follow first-order kinetics.
      Generally, they are sonicated more rapidly in polar than in non-polar solvent;
      higher volatility of the solute results in faster sonolysis in the organic
      solvents. However, the sonication of cyclohexane in n-decane and the sonication
      of benzene in n-propanol are exceptional cases. Since cyclohexane exhibits a much
      higher lipophilicity and benzene a much higher hydrophilicity than other educts,
      it might be more difficult to transfer either educt from the bulk liquid into the
      cavitation bubbles. In tetrachloroethylene, the reactivity of the tested educts
      with in situ generated chlorine as well as chlorine-containing radical
      intermediates can accelerate the rate of sonochemical reactions under the
      employed conditions. In n-propanol and n-decane, the pyrolysis during the
      collapse of the cavitation bubbles is the only reaction pathway of sonolysis. In
      tetrachloroethylene, the pyrolysis during the collapse of the cavitation bubbles
      and the free radical reaction in the bulk liquid may occur simultaneously. Except
      for the products generated from sonolysis, products formed from chlorine
      transformations (substitution or addition reactions) are detected. Benzene is
      hardly decomposed in tetrachloroethylene. However, when FeCl3 is added into the
      reaction system, benzene is sonoconverted rapidly, and the product chlorobenzene
      was detected. In organic solvents, the sonoreaction rates and the sonoproducts
      are dependent on the physicochemical properties of the solvents used, as well as
      the volatility, the polarity and the reactivity of educts.

PMID- 15474966
TI  - Benzene formation during aquasonolysis of selected cyclic C6Hx hydrocarbons.
AB  - Yield and selectivity of benzene produced from aquasonolysis of the selected
      cyclic C6Hx hydrocarbons, i.e., 1,4-cyclohexadiene, 1,3-cyclohexadiene,
      cyclohexene, cyclohexane, and methylcyclopentane, have been investigated in this
      work. Benzene cannot be detected during the aquasonolysis of cyclohexane and
      methylcyclopentane. The order of yield and selectivity of benzene was as follows:
      1,4-cyclohexadiene>>1,3-cyclohexadiene>>cyclohexene. The initial concentrations
      of substrates can affect the yield of benzene. During the aquasonolysis of 1,3
      cyclohexadiene and cyclohexene, other C6 species except benzene were also found.
      It was suggested that benzene could directly be generated by formal
      dehydrogenation of cyclic C6Hx hydrocarbons.

PMID- 15474967
TI  - A combination of ultrasound and inorganic catalyst: removal of 2-chlorophenol
      from aqueous solution.
AB  - Removal of 2-chlorophenol by ultrasonic waves (sonolysis), inorganic catalyst,
      and a combination of the two processes was tested and compared with each
      technique. In sonolysis, 2-chlorophenol mostly degraded indirectly in the bulk of
      solution by the radicals produced in the cavitation process. In catalyst
      treatment, the removal was performed in the presence of Al2O3, TiO2 and CuO. The
      highest removal was achieved in the presence of TiO2 for this pollutant. In the
      combined method an enhancement was observed for the removal of 2-chlorophenol.
      This could be attributed primarily to the continuous cleaning and chemical
      activation of the catalyst by acoustic cavitation. The mass transfer between the
      liquid phase and the catalyst and also the surface area of the catalyst are
      accelerated by the ultrasonic waves. The removal of 2-chlorophenol was performed
      under different intensities of irradiation, temperatures and quantities of
      catalyst. Some experiments were conducted in the presence of a Fenton reagent. In
      kinetic point of view, the removal of pollutant showed a pseudo-first order
      behavior. The combined method had a higher rate coefficient than sonolysis and
      catalyst treatment individually. Under some conditions, the presence of
      ultrasound has increased the rate coefficient of removal to about 10 times that
      in the absence of ultrasound.

PMID- 15474968
TI  - Dendritic cells: limited potential in immunotherapy.
AB  - Dendritic cells (DC) represent the most potent antigen-presenting cells (APC) of
      the immune system for their unique capability of presenting antigen to T-cells.
      Their use as cellular vaccines after charging with antigen ex vivo has been shown
      to induce protective and therapeutic anti-tumor immunity with regression of tumor
      manifestations in animal models of experimental cancer therapy. Human monocyte
      derived DC (MoDC) generated in vitro in the presence of GM-CSF and IL-4 are
      regarded equivalent to immature DC. They can be induced to mature under various
      experimental conditions. MoDC, in their immature as well as mature state have
      been widely used for experimental as well as for clinical purposes. However,
      unequivocal proof for the clinical efficiency of MoDC-based anti-tumor
      vaccinations is still missing. There is now increasing experimental evidence
      demonstrating that MoDC may be hampered in their ability to migrate in response
      to inflammatory as well as homeostatic chemataxins. We therefore suggest that
      MoDC may not represent the equivalent of migratory DC in vivo limiting their use
      as magic bullets in tumor immunotherapy.

PMID- 15474969
TI  - The spermatogonial stem cell: from basic knowledge to transgenic technology.
AB  - Differentiation of germ cells in the testis originates from a constantly renewed
      small pool of stem cells. They give rise to the first differentiated
      spermatogenic cells (spermatogonia). These committed cells will then follow a
      strictly defined succession of steps, starting with six synchronized mitotic
      cycles before reaching the first meiotic stages. Following a first identification
      of the spermatogonial stem cells on morphological and cytological criteria, a
      functional assay was devised, based on their ability to repopulate the testis of
      a sterile recipient. Purification and characterization of the stem fraction is in
      progress. Fundamental knowledge of the biology of the germ line and preclinical
      studies in several important fields will benefit of these advances, while gene
      transfer prior to reimplantation opens a new approach in transgenic technology.

PMID- 15474970
TI  - BAG-1: a multi-functional pro-survival molecule.
AB  - BAG-1 is a multi-functional protein that exists as three functionally distinct
      and differentially localized isoforms which originate from a single mRNA and
      interact with a wide range of cellular targets. These include heat shock
      proteins, nuclear hormone receptors, signalling molecules, the anti-apoptotic BCL
      2 protein and components of the ubiquitylation/proteasome machinery.
      Overexpression of BAG-1 isoforms has been demonstrated to regulate apoptosis,
      proliferation, transcription, metastasis and cell motility in a wide variety of
      cell systems. Since BAG-1 has a role in many biological pathways there is
      increasing evidence supporting the view that BAG-1 is an important molecule in
      disease, for example, potentially modulating both cell survival and response to
      nuclear hormones in breast cancer, and BAG-1 is a potential molecular target for
      therapeutic intervention.

PMID- 15474971
TI  - Calreticulin, a Ca2+-binding chaperone of the endoplasmic reticulum.
AB  - Calreticulin is a 46-kDa Ca2+-binding chaperone found across a diverse range of
      species. The protein is involved in the regulation of intracellular Ca2+
      homeostasis and endoplasmic reticulum (ER) Ca2+ storage capacity. Calreticulin is
      also an important molecular chaperone involved in "quality control" within
      secretory pathways. The protein contains structurally and functionally unique
      domains with specialized functions. Studies on calreticulin knockout mice
      indicate that the protein is essential in early cardiac development. The protein
      also plays an important role in autoimmunity and cancer.

PMID- 15474972
TI  - Mcl-1.
AB  - Mcl-1 is a Bcl-2 family protein which can act as an apical molecule in apoptosis
      control, promoting cell survival by interfering at an early stage in a cascade of
      events leading to release of cytochrome c from mitochondria. Mcl-1 has a short
      half life and is a highly regulated protein, induced by a wide range of survival
      signals and also rapidly down regulated during apoptosis. Mcl-1 can also readily
      be cleaved by caspases during apoptosis to produce a cell death promoting
      molecule. The multiple levels of control of Mcl-1 expression suggest that Mcl-1
      plays a critical role in controlling life and death decisions in response to
      rapidly changing environmental cues and Mcl-1 is required for embryonic
      development and the function of the immune system. Expression of Mcl-1 may be
      useful in informing decision making in the treatment of various cancers, and
      countering Mcl-1 function may be an attractive therapeutic strategy in
      malignancy, inflammatory conditions and infectious disease where Mcl-1 may play a
      major role in suppressing apoptosis.

PMID- 15474973
TI  - Aminolevulinic acid: from its unique biological function to its star role in
      photodynamic therapy.
AB  - Porphyrins are molecules essential for life. They are involved in the key
      processes of photosynthesis and respiration. The biosynthesis of tetrapyrroles in
      all living cells occurs through several steps where the formation of
      aminolevulinic acid (ALA) is the first committed intermediate. Two alternative
      routes for the formation of ALA have been proposed: one involves the condensation
      of Succinyl CoA and glycine catalyzed by ALA synthetase taking place in the
      mitochondria, and the second one is the so called 5-carbon route, occurring in
      the stroma of plastids. Eight molecules of ALA are used in the formation of
      protoporphyrin IX. Specific deficiencies in one of the enzymes of the heme
      pathway produce the porphyrias. In the acute porphyrias, the pathogenesis of the
      neurological dysfunction is attributed to the accumulation of ALA. Fluorescent
      and photosensitizing properties of protoporphyrin accumulated after the exogenous
      administration of ALA, can be used to visualize and destroy malignant cells in
      the so-called photodynamic diagnosis (PDD) and photodynamic therapy (PDT) of
      cancer. Many clinical ALA-PDT applications to malignant and non-malignant
      pathologies are currently in use. Different approaches to enhance ALA penetration
      in cells are under investigation, including the use of more lipophilic ALA
      derivatives and studies of the transport mechanisms of ALA. ALA has also been
      proposed to be used as a biodegradable herbicide, as an insecticide and as a
      plant growth regulator.

PMID- 15474974
TI  - Voltage-dependent anion-selective channel 1 (VDAC1)--a mitochondrial protein,
      rediscovered as a novel enzyme in the plasma membrane.
AB  - The eukaryotic porin or voltage-dependent anion-selective channel (VDAC1) is a
      pore-forming protein discovered twenty five years ago in the mitochondrial outer
      membrane. Its gene in eukaryotes is known, but its tertiary structure has never
      been solved. Structure predictions highlight the presence of several amphipathic
      beta-strands possibly organised in a beta-barrel. VDAC1 has recently been
      described as being a NADH:ferricyanide reductase in the plasma membrane. There it
      affects the regulation of cell growth and death. Physiological cell death
      (apoptosis) has become a major research focus of biomedical research. Regulation
      of the enzyme will have impacts on cancer and autoimmune diseases (insufficient
      apoptosis) as well as neurodegenerative diseases (excessive apoptosis). VDAC1 in
      the plasma membrane establishes a novel level of apoptosis regulation putatively
      via its redox activity.

PMID- 15474975
TI  - MMP-1: the elder of the family.
AB  - The matrix metalloproteinases (MMPs) are a family of zinc-containing
      endopeptidases that play a key role in both physiological and pathological tissue
      remodeling. Human fibroblast collagenase (MMP-1) was the first vertebrate
      collagenase purified as a protein and cloned as a cDNA, and is considered the
      prototype for all the interstitial collagenases. It is synthesized as a zymogen
      where N-terminal residues are removed by proteolysis and shares with other MMPs a
      catalytic domain and a carboxy terminal domain with sequence similarity to
      hemopexin. Importantly, MMP-1 should be considered a multifunctional molecule
      since it participates not only in the turnover of collagen fibrils in the
      extracellular space but also in the cleavage of a number of non-matrix substrates
      and cell surface molecules suggesting a role in the regulation of cellular
      behaviour. Furthermore, an extensive body of evidence indicates that MMP-1 plays
      an important role in diverse physiologic processes such as development, tissue
      morphogenesis, and wound repair. Likewise, it seems to be implicated in a variety
      of human diseases including cancer, rheumatoid arthritis, pulmonary emphysema and
      fibrotic disorders, suggesting that its inhibition or stimulation may open
      therapeutic avenues.

PMID- 15474976
TI  - The role of inflammation in Alzheimer's disease.
AB  - Considerable evidence gained over the past decade has supported the conclusion
      that neuroinflammation is associated with Alzheimer's disease (AD) pathology.
      Inflammatory components related to AD neuroinflammation include brain cells such
      as microglia and astrocytes, the classic and alternate pathways of the complement
      system, the pentraxin acute-phase proteins, neuronal-type nicotinic acetylcholine
      receptors (AChRs), peroxisomal proliferators-activated receptors (PPARs), as well
      as cytokines and chemokines. Both the microglia and astrocytes have been shown to
      generate beta-amyloid protein (Abeta), one of the main pathologic features of AD.
      Abeta itself has been shown to act as a pro-inflammatory agent causing the
      activation of many of the inflammatory components. Further substantiation for the
      role of neuroinflammation in AD has come from studies that demonstrate patients
      who took non-steroidal anti-inflammatory drugs had a lower risk of AD than those
      who did not. These same results have led to increased interest in pursuing anti
      inflammatory therapy for AD but with poor results. On the other hand, increasing
      amount of data suggest that AChRs and PPARs are involved in AD-induced
      neuroinflammation and in this regard, future therapy may focus on their specific
      targeting in the AD brain.

PMID- 15474977
TI  - Meso-substituted tetra-cationic porphyrins photosensitize the death of human
      fibrosarcoma cells via lysosomal targeting.
AB  - In this paper we present a study on the intracellular localisation and the
      efficiency of cell photoinactivation of a series of derivatives of 5,10,15,20
      tetrakis-(4-N-methylpyridyl)-porphine (C1), whose degree of lipophilicity was
      varied through replacement of one methyl group with an alkyl chain of various
      length. Human HT1080 fibrosarcoma cells exposed to the various C1 derivatives
      (0.25 microM) for 24 h and irradiated with increasing doses of red-light (0.45-27
      J/cm2) were inactivated with different efficiencies. The efficiency of cell
      photoinactivation increased with the increasing length of the hydrocarbon tail
      and lipophilicity and correlated with the efficiency of the porphyrin
      accumulation into the cells. Despite the presence of positive charges, these
      porphyrins did localise rather selectively in lysosomes while mitochondrial
      localisation was not evident, as demonstrated by fluorescence microscopy studies.
      Studies on isolated mitochondria provided evidence that the porphyrin uptake and
      distribution in these organelles were not modulated by the transmembrane
      potential but were exclusively controlled by partitioning phenomena which might
      have prevented mitochondria localization in whole cells. Our findings
      demonstrated that these porphyrins entered the cells through the endocytotic
      pathway and were transported to lysosomes whose pH increased rapidly upon
      irradiation. Lysosomal damage did not cause any intracellular redistribution of
      the porphyrin and represented the primary event causing cell death, very likely
      via necrosis.

PMID- 15474978
TI  - Native and modified C-reactive protein bind different receptors on human
      neutrophils.
AB  - Native C-reactive protein (CRP) is a planar pentamer of identical subunits
      expressed at high serum levels during the acute phase of inflammation. At
      inflammatory sites, an isomeric form termed modified CRP (mCRP) is expressed and
      reveals neoantigenic epitopes associated with modified monomeric CRP subunits.
      mCRP cannot assume the native pentameric conformation but rather forms a
      nonpentameric aggregate of monomers. While native CRP inhibits neutrophil
      movement in vitro and in vivo, the effect of mCRP on neutrophil movement has not
      been reported. To model the biological function and biochemical interaction of
      mCRP on neutrophils, in vitro chemotaxis and binding experiments were performed
      using mCRP. Reported here, mCRP effectively inhibited fMLP-induced chemotaxis
      similar to native CRP. Additionally, mCRP increased binding of labeled native CRP
      to neutrophils. This increased binding occurred by direct protein-protein
      interaction of the C-terminus thereby implicating the CRP(199-206) sequence.
      Binding of mCRP to neutrophils was blocked by anti-CD16 monoclonal antibody
      whereas native CRP was not. These results suggest that modified forms of CRP
      inhibit chemotaxis, a function similar to native CRP, but that mCRP and native
      molecule bind different receptors on human neutrophils.

PMID- 15474979
TI  - Fitting modified HRP-I peptide analogue 3D structure into HLA-DR molecules
      induces protection against Plasmodium falciparum malaria.
AB  - Conserved, high-activity, red blood cell binding malaria peptide 6786, from the
      HRP-I protein, having a random 3D structure as determined by 1H-NMR, was non
      immunogenic and non-protection inducing when used as an immunogen in Aotus
      monkeys. Modifications made in its amino acid sequence were thus performed to
      render it immunogenic and protection inducing. Non-immunogenic, non-protection
      inducing modified peptide 13852 presented A2-H8 and K14-L18 helix fragments.
      Immunogenic, non-protection inducing modified peptide 23428 presented a short,
      displaced helix in a different region, whilst immunogenic, protection inducing
      peptide 24224 had 2 displaced helical regions towards the central region giving
      more flexibility to its N- and C-terminals. Immunogenic and protection inducing
      peptides bound with high affinity to HLA-DRB1* 0301 whilst others did not bind to
      any HLA-DRB1* purified molecule. Structural modifications may thus lead to
      inducing immunogenicity and protection associated with their capacity to bind
      specifically to purified HLA-DRB1* molecules, suggesting a new way of developing
      multi-component, subunit-based malarial vaccines.

PMID- 15474980
TI  - Identification and characterization of a novel splice variant of beta3 subunit of
      GABA(A) receptor in rat testis and spermatozoa.
AB  - Gamma-aminobutyric acid type A (GABA(A)) receptors are the major sites of
      inhibitory action of fast synaptic neurotransmission in the brain. Their
      receptors are also widely distributed in peripheral and endocrine tissues. A full
      length cDNA encoding a novel splice variant of beta3 subunit of GABA(A) receptor,
      designated as beta3t, was identified in rat testis. This isoform contains a
      segment, having identical amino acid sequence as the beta3 subunit of neuronal
      GABA(A) receptors except for a section composed of 25 different amino acid
      sequence in the N-terminus. Northern blot shows that this isoform is found in rat
      testis. The beta3t isoform mRNA was detected in germ cells in the late step of
      spermatogenesis by in situ hybridization assay. Results of immunohistochemical
      and immunocytochemical assays indicate that the beta3t isoform is expressed in
      rat testis and spermatozoa. To determine a possible function of the N-terminal 25
      amino acid segment, a recombinant plasmid of beta3t-EGFPC was constructed by
      fusing green fluorescent protein to the C-terminus of the beta3t isoform. The
      chimera product failed to be translocated unto the cell surface when expressed in
      HEK 293 cells; whereas, the beta3 subunit of rat brain is incorporated into the
      plasma membrane. In conclusion, the present results show that one variant of
      beta3 subunit of GABA(A) receptor, designated as beta3t, is found in germ cells
      of rat testis and sperm. The inability of the beta3t variant to target into the
      plasma membrane maybe a consequence of the unique 25 amino acid segment in the N
      terminus.

PMID- 15474981
TI  - Influence of salts and alcohols on the conformation of partially folded
      intermediate of stem bromelain at low pH.
AB  - The effect of salts and alcohols was examined on the partially folded
      intermediate (PFI) state of stem bromelain reported at low pH (Haq, Rasheedi, and
      Khan (2002) European Journal of Biochemistry 269, 47-52) by a combination of
      optical methods like circular dichroism, intrinsic fluorescence and ANS binding.
      ESI mass spectrometry was also performed to see the effect, if any, on the
      overall tertiary structure of the protein. Increase in ionic strength by the
      addition of salts resulted in folded structures somewhat different from the
      native enzyme. Salt-induced intermediates are characterized by increase in
      helical content and a significantly reduced exposure of hydrophobic clusters
      relative to the state at pH 2.0. The emission wavelength maximum of intrinsic
      fluorescence was shifted towards that of native enzyme. ESI-MS data show
      decreased accessibility of ionizable/protonation sites suggestive of a folded
      structure. On the other hand, alcohol-induced intermediates though exhibiting
      increased helical content are apparently largely unfolded as observed by ESI.
      Thermal denaturation of a representative intermediate, each from the group of
      salts and alcohols examined, was also performed to check their relative
      stabilities. While the alcohol-induced state showed a cooperative thermal
      transition, the salt-induced state shows non-cooperative thermal denaturation.

PMID- 15474982
TI  - PGE2 induces the gene expression of bone matrix metalloproteinase-1 in mouse
      osteoblasts by cAMP-PKA signaling pathway.
AB  - Prostaglandin E2 (PGE2), an abundant eicosanoid in bone, has been implicated in a
      number of pathological states associated with bone loss, and is also known to
      stimulate matrix metalloproteinase (MMP)-1 synthesis and secretion in rat and
      human osteoblast cells, although the nature of the intracellular reaction remains
      unclear. Although MMP-1 plays a critical role in bone-remodeling, it would be of
      interest to examine whether PGE2 regulates MMP-1 expression by mouse osteoblasts
      or not. Here we demonstrate that PGE2 is a potent inducer of MMP-1 production in
      fetal osteoblasts and show that PGE2 stimulates the activity of the MMP-1
      promoter in osteoblasts, suggesting that PGE2 controls MMP-1 gene expression at
      least at the transcriptional level. PGE2 induced MMP-1 messenger RNA (mRNA)
      expression in the cells within 4 h, and this expression was maintained for 36 h.
      The increase in MMP-1 production with 0.1-2.0 microM PGE2 was dose-dependent. We
      also found that PGE2 (1.5 microM) up-regulated MMP-1 protein levels in cultured
      mouse osteoblasts, as evidenced by ELISA. To examine whether PGE2 mediated
      response and signal pathway are involved in the intracellular action, the PGE2
      mediated expression of the MMP-1 gene was investigated in mouse osteoblast cells.
      A Northern blot analysis showed that PGE2 and PGE1 were potent stimulators of MMP
      1 transcription, and the presence of thromboxane B2 had no effect. The increase
      in MMP-1 transcript after PGE2 treatment was observed at 4h, reaching a maximum
      at 6h, and persisted for 24h. This response was dose-dependent. Cycloheximide, an
      inhibitor of protein synthesis, completely blocked this effect by PGE2,
      indicating that the expression of other genes is also required. The second
      messenger analog, 8-bromo-cAMP, mimicked the effects of PGE2 by stimulating a
      dose-dependent increase in MMP-1 mRNA levels, with a maximal effect that was
      quantitatively similar to that observed with PGE2. Thus, the present results
      strongly suggest that the PGE2 stimulation of MMP-1 synthesis is due to the
      activation of MMP-1 gene transcription and a subsequent marked increase in MMP-1
      transcription. This effect is dependent on de novo protein synthesis and is
      mimicked by protein kinase A activation. The findings suggest that PGE2 is
      involved in the cAMP-PKA signaling pathway in regulating MMP-1 gene expression in
      osteoblasts.

PMID- 15474983
TI  - Characterization of purified rat testicular transglutaminase and age-dependent
      changes of the enzyme activities.
AB  - The Ca2+-dependent tissue transglutaminase is widely distributed in various
      tissues and has been reported to participate in many cellular growth and
      differentiation processes. In the past decade, tissue transglutaminase is also
      identified as a G protein, G(alphah), for intercellular signaling. To further
      characterize testicular transglutaminase, the rat testicular transglutaminase was
      purified by ammonium sulfate precipitation, DEAE ion-exchange, heparin-agarose,
      and GTP-agarose affinity chromatographies. This purification protocol resulted in
      a 8400-fold enrichment of the enzyme with a reproducible 15% yield. The purified
      enzyme showed as a single band of 78kDa on SDS-polyacrylamide gel. Western blot
      analysis using anti-liver tissue transglutaminase monoclonal antibody also
      recognized the enzyme, indicating it is a t-TGase in nature. The Km values of
      purified testicular transglutaminase for putrescine and N,N-dimethylcasein were
      determined to be 35 and 17 microM, respectively. Its transglutaminase cross
      linking activity was strongly inhibited by EGTA, GTP, polyamines, and cystamine,
      as well as moderately by ATP and NaCl. The enzyme exhibited a magnesium-dependent
      GTP-hydrolyzing capacity, but its GTP-binding activity did not require magnesium.
      Furthermore, the enzyme activity was found to be closely related with the first
      wave of spermatogenesis. Thus, testicular transglutaminase is speculated to
      participate in the event of spermatogenesis. In conclusion, the purified
      testicular transglutaminase displays property of either the tissue-type
      transglutaminase, or the GTP-binding and hydrolyzing characteristics. The
      activity of testicular transglutaminase is age-dependent, greatly stimulated
      during the first wave of spermatogenesis.

PMID- 15474984
TI  - Elevation of galectin-9 as an inflammatory response in the periodontal ligament
      cells exposed to Porphylomonas gingivalis lipopolysaccharide in vitro and in
      vivo.
AB  - Considerable evidence suggests that periodontal disease not only is caused by
      bacterial infection but also is associated with host susceptibility. Using in
      house cDNA microarray analysis, we attempted to identify gene expression changes
      in human periodontal ligament (PDL)-derived cells with and without treatment with
      lipopolysaccharide (LPS) extracted from Porphylomonas gingivalis (P. gingivalis
      LPS). Of the five up-regulated genes in the PDLs treated with P. gingivalis LPS,
      galectin-9, which was reported to have eosinophil chemoattraction, was selected
      for further analyses. By semiquantitative reverse transcriptase-polymerase chain
      reaction (sqRT-PCR), real-time quantitative RT-PCR, and Western blot analyses,
      elevated galectin-9 gene expression was detected in LPS-treated PDL-derived
      cells. Consequently, it was confirmed that the LPS enhances the expression level
      of galectin-9 mRNA and protein in a time-dependent manner together with
      interleukin-8. In addition, strong immunoreaction for galectin-9 was detected in
      the PDL consisting of the periodontal pocket of a patient with severe periodontal
      disease. Furthermore, significant up-regulation of galectin-9 mRNA expression was
      detected in the mRNA from PDLs of patients with periodontal disease when compared
      with healthy donors (P < 0.05). These results suggest that galectin-9 expression
      is associated with inflammatory reactions in the PDL.

PMID- 15474985
TI  - Preferential loss of 5S and 28S rDNA genes in human adipose tissue during ageing.
AB  - Loss of genomic rDNA has been associated with cellular and organismal ageing. The
      rDNA locus in humans comprises multiple copies of the 5.8S, 28S and 18S genes.
      Aim of the present study was to test the effect of aging on the copy number of
      the three rDNA genes individually in post-mitotic human tissue. We utilized real
      time polymerase chain reaction relative quantification to measure the copy number
      of 5.8S, 28S and 18S rDNA genes individually. We obtained adipose tissue from 120
      male individuals aged from 9 to 94 years. The available data of each subject
      corresponding to the time of tissue sampling included: age, height, weight and
      calculated body mass index. Each rDNA gene was directly tested with Pearson
      correlation against age and body mass index. We found a significant negative
      correlation of the gene copy of 5.8S (P < 0.001) and 28S (P < 0.003) with age.
      Interestingly 18S gene copy displayed a different pattern with no statistically
      significant correlation with age. Conversely, we observed a significant negative
      correlation of the 18S gene copy with body mass index (P = 0.004) and a
      marginally non-significant negative correlation of the 5.8S (P = 0.097) gene copy
      with body mass index. In summary our results indicate that the rDNA recombination
      events in humans can be differentially targeted and regulated in response to
      ageing and/or fat accumulation. The proposed model generates possible
      implications regarding the effects of each rDNA gene loss in cell function as
      well as the mechanism of recombination targeting.

PMID- 15474986
TI  - p53 protein activates the transcription of human proliferating cell nuclear
      antigen in response to 4-nitroquinoline N-oxide treatment.
AB  - 4-nitroquinoline N-oxide (4-NQO) is a potent mutagen and carcinogen. To elucidate
      the cellular response to 4-NQO, we studied the transcriptional regulation of
      human proliferating cell nuclear antigen (hPCNA), an essential protein in DNA
      replication and repair, after 4-NQO treatment. We found that hPCNA promoter was
      dose-dependently transactivated by 4-NQO under the concentration of 2 microM via
      a previously reported p53-binding element located from -236 to -217 upstream of
      the transcription start site. Based on our western blot analysis, the
      phosphorylation of serine at the 15th residue (Ser15) of p53 was activated by 4
      NQO, whereas the level of p53 in the cells did not change much. It was observed
      that Staurosporine, a Ser/Thr kinase inhibitor, blocked the Ser15 phosphorylation
      of p53 and the hPCNA promoter response to 4-NQO simultaneously, suggesting that
      Ser15 phosphorylated p53 was the 4-NQO-responsive hPCNA regulator. The [3H]
      thymidine deoxyribose (TdR) incorporation assay and the comet assay showed that
      DNA repair was triggered when DNA replication was inhibited after the treatment
      of 4-NQO, and the hPCNA transactivation seemed to contribute to DNA repair. Taken
      together, our data indicate that after 4-NQO treatment hPCNA is transactivated by
      Ser15 phosphorylated p53, and participate in DNA repair.

PMID- 15474987
TI  - Magnolol and honokiol enhance HL-60 human leukemia cell differentiation induced
      by 1,25-dihydroxyvitamin D3 and retinoic acid.
AB  - Magnolol (MG) and honokiol (HK), two lignans showing anti-inflammatory and anti
      oxidant properties and abundantly available in the medicinal plants Magnolia
      officinalis and M. obovata, were found to enhance HL-60 cell differentiation
      initiated by low doses of 1,25-dihydroxyvitamin D3 (VD3) and all-trans-retinoic
      acid (ATRA). Cells expressing membrane differentiation markers CD11b and CD14
      were increased from 4% in non-treated control to 8-16% after being treated with
      10-30 microM MG or HK. When added to 1 nM VD3, MG or HK increased markers
      expressing cells from approximately 30% to 50-80%. When either MG or HK was added
      to 20 nM ATRA, only CD11b, but not CD14, expressing cells were increased from 9%
      to 24-70%. Under the same conditions, adding MG or HK to VD3 or ATRA treatment
      further enlarged the G0/G1 cell population and increased the expression of
      p27(Kip1), a cyclin-dependent kinase inhibitor. Pharmacological studies using
      PD098059 (a MEK inhibitor), SB203580 (a p38 MAPK inhibitor) and SP600125 (a JNK
      inhibitor) suggested that the MEK pathway was important for VD3 and ATRA-induced
      differentiation and also its enhancement by MG or HK, the p38 MAPK pathway had a
      inhibitory effect and the JNK pathway had little influence. It is evident that MG
      and HK are potential differentiation enhancing agents which may allow the use of
      low doses of VD3 and ATRA in the treatment for acute promyelocytic leukemia.

PMID- 15474988
TI  - Interleukin-6 is a potent inducer of S100P, which is up-regulated in androgen
      refractory and metastatic prostate cancer.
AB  - Elevated circulating interleukin-6 (IL6) and up-regulated S100P in prostate
      cancer (PCa) specimens correlate independently with progression to androgen
      independent and metastatic PCa. The cause of up-regulated S100P levels in
      advanced PCa remains to be determined. We investigated the possibility that IL6
      is an inducer of S100P. Determination of mRNA and protein levels by real-time PCR
      and Western blotting revealed that IL6 is a more potent inducer of S100P than the
      synthetic androgen, R1881, in the LNCaP/C4-2B model of PCa progression. IL6 did
      not require androgen to induce S100P in these cells, which express a functional
      androgen receptor (AR). Like R1881, IL6 was unable to induce S100P in PC3 cells
      that lack a functional AR. IL6 did not strongly induce the AR-dependent genes PSA
      and KLK2 and, contrary to R1881, down-regulated Cyr61/CCN1, a potential marker
      that is down-regulated in PCa. Epidermal growth factor (EGF), which like IL6 is a
      non-androgen activator of the AR, did not induce S100P. The data identifies a
      unique gene-induction profile for IL6 and suggests that IL6 may require a
      functional AR for S100P induction. A link between elevated IL6 and up-regulated
      S100P in androgen-refractory and metastatic PCa is postulated.

PMID- 15474989
TI  - Immunomodulatory role of native and heat denatured agglutinin from Abrus
      precatorius.
AB  - Lectins are known as polyclonal activators of lymphocytes and work through the
      induction of battery of cytokines, which vary from lectin to lectin. Most widely
      used biological response modifier Mistletoe lectin (ML-1) in therapy stimulates
      lymphocytes, macrophages, and natural killer cells and induces both TH1 and TH2
      type cytokines. Abrus agglutinin, similar to ML-1 with respect to carbohydrate
      specificity [gal (beta1-->3) gal/Nac], was studied both in native (NA) and heat
      denatured (HDA) condition for murine splenocyte proliferation, cytokine
      secretion, NK-cell activation, and thymocyte proliferation in vitro with a view
      to assess its potential as an immunomodulator. Both NA and HDA activate
      splenocytes and induce production of cytokines like IL-2, IFN-gamma and TNF
      alphabeta indicating a TH1 type of immune response. Native agglutinin and HDA
      induced conditioned media of adherent splenocytes could stimulate non-adherent
      splenocytes and vice versa. Heat denatured agglutinin was able to induce NK-cell
      activation at much lower concentration than that of NA, but the extent of NK-cell
      activation was higher for NA. Proliferation of thymocytes by NA and HDA was also
      observed. This study indicates that Abrus agglutinin could be a potential
      immunomodulator both in native as well as in heat denatured form.

PMID- 15474990
TI  - Developmentally regulated cytoplasmic retention of the transcription factor XMI
      ER1 requires sequence in the acidic activation domain.
AB  - Xmi-er1 is a fibroblast growth factor regulated immediate-early gene that is
      activated during mesoderm induction in Xenopus embryonic explants. This gene
      encodes a nuclear protein with potent transcriptional regulator activity and
      overexpression of XMI-ER1 in Xenopus embryos inhibits mesoderm induction and
      leads to truncations along the anteroposterior axis. We showed previously that
      XMI-ER1 is retained in the cytoplasm during cleavage stages and only begins to
      appear in the nucleus at mid-blastula. Such developmentally regulated nuclear
      translocation may represent an important mechanism for regulating XMI-ER1
      activity in the early embryo. Here, we investigate different mechanisms that
      might control nuclear translocation of XMI-ER1. Using alpha-amanitin to inhibit
      transcription, we show that nuclear localization is not dependent on zygotic
      transcription. Nor is it the result of a developmentally regulated import
      pathway, as the XMI-ER1 nuclear localization signal (NLS) fused to beta
      galactosidase (betagal) was able to direct nuclear translocation prior to mid
      blastula. Fusion of an additional, heterologous NLS to the N-terminus of XMI-ER1
      was not sufficient to overcome cytoplasmic retention, indicating that retention
      does not involve NLS masking, but rather binding to a cytoplasmic anchor. The
      anchoring molecule is not an RNA, as microinjection of RNase A did not affect the
      timing of nuclear translocation. Western blot analysis using antibodies that
      recognize phosphorylated residues revealed that, while XMI-ER1 is not itself
      phosphorylated, it is associated with two differentially phosphorylated proteins,
      suggesting that the anchoring mechanism may involve interaction with a
      cytoplasmic protein(s). A series of XMI-ER1 deletion mutants was utilized to map
      the putative retention domain. Our analysis revealed that amino acids 144-175,
      containing the fourth acidic stretch of the acidic activation domain, are
      required for retention. These results suggest that XMI-ER1 is retained in the
      cytoplasm of the early embryo by interaction of the region containing amino acids
      144-175 with a cytoplasmic anchor.

PMID- 15474991
TI  - Laminin-1 is phosphorylated by ecto-protein kinases of monocytes.
AB  - Monocytes encounter basement membranes and interact with laminins while crossing
      the vascular barrier. It is known that these cells possess ecto-protein kinase
      activity on their surface. Several proteins of the extracellular matrix can be
      phosphorylated by ectokinases. Therefore, it has been hypothesized that monocyte
      ectokinases could phosphorylate laminins and influence their biological
      properties. In order to test the above hypothesis, we used intact human monocytes
      and adenosine triphosphate labeled with radioactive phosphate at the third
      phosphate ([gamma-32P]-ATP) to phosphorylate laminin-1. Autoradiography after
      sodium dodecyl sulphate polyacrylamyde gel electrophoresis (SDS-PAGE)
      electrophoresis indicated phosphorylation of laminin-1 on the beta and/or gamma
      chains. After phosphorylation, phosphoserine could be detected on Western blots
      by a specific monoclonal antibody. Phosphorylation was not detected when
      monocytes were pre-treated with trypsin and was inhibited by a specific ecto
      protein kinase inhibitor (K252b). Laminin phosphorylation was also inhibited by
      heparin, a known inhibitor of casein kinase II and by pretreatment of monocytes
      by a monoclonal anti-casein kinase II antibody. Heparin binding, cell attachment
      and proliferation, and monocyte migration were enhanced on the phosphorylated
      laminin-1 as compared to the non-phosphorylated controls. These data indicate
      that laminin-1 can be phosphorylated by monocyte casein kinase II type
      ectokinase. This phosphorylation influences important functions of laminin and
      therefore could provide an additional means for the interaction of monocytes with
      basement membranes.

PMID- 15474992
TI  - Extracellular matrix-dependent myosin dynamics during G1-S phase cell cycle
      progression in hepatocytes.
AB  - Cell spreading and proliferation are tightly coupled in anchorage-dependent
      cells. While adhesion-dependent proliferation signals require an intact actin
      cytoskeleton, and some of these signals such as ERK activation have been
      characterized, the role of myosin in spreading and cell cycle progression under
      different extracellular matrix (ECM) conditions is not known. Studies presented
      here examine changes in myosin activity in freshly isolated hepatocytes under ECM
      conditions that promote either proliferation (high fibronectin density) or growth
      arrest (low fibronectin density). Three different measures were obtained and
      related to both spreading and cell cycle progression: myosin protein levels and
      association with cytoskeleton, myosin light chain phosphorylation, and its ATPase
      activity. During the first 48 h in culture, corresponding with transit through G1
      phase, there was a six-fold increase in both myosin protein levels and myosin
      association with actin cytoskeleton. There was also a steady increase in myosin
      light chain phosphorylation and ATPase activity with spreading, which did not
      occur in non-spread, growth-arrested cells on low density of fibronectin. Myosin
      inhibiting drugs blocked ERK activation, cyclin D1 expression, and S phase entry.
      Overexpression of the cell cycle protein cyclin D1 overcame both ECM-dependent
      and actomyosin-dependent inhibition of DNA synthesis, suggesting that cyclin D1
      is a key event downstream of myosin-dependent cell cycle regulation.

PMID- 15474993
TI  - A versatile in vitro assay for investigating angiogenesis of the heart.
AB  - Neovascularization in the heart is usually investigated with models of
      angiogenesis in vivo. Here we present a simple model that allows investigating
      heart angiogenesis in mice and rats in vitro. Small pieces of left ventricular
      myocardium were cultured in three-dimensional fibrin gels for 10 days. A single
      mouse heart allowed assessing 24 conditions, each tested in octuplicates. Rat
      recombinant VEGF164, human recombinant bFGF, and human recombinant PDGF-BB were
      used under normoxia (21% O2) and hypoxia (3% O2), and outgrowth of endothelial
      sprouts from heart pieces was quantified. In 4-week-old OF1 mice, endothelial
      sprouts formed spontaneously. In contrast, in 12-week-old adult mice, virtually
      no sprouts formed under normoxia. Under hypoxia, sprout formation increased
      substantially. Different growth factors induced formation of distinct patterns of
      sprouts and unorganized single cells. Sprouts were composed of endothelial cells
      with smooth muscle cells or pericytes interacting with them, as assessed by
      immunohistochemistry. Taken together, our model is suited for investigation of
      angiogenesis of the heart in vitro. It may allow performing extensive series of
      experiments in vitro including rapid screening of pharmacological compounds and
      assessment of mechanisms of heart angiogenesis in transgenic animals in an easy
      straightforward manner.

PMID- 15474994
TI  - PAP-1, the mutated gene underlying the RP9 form of dominant retinitis pigmentosa,
      is a splicing factor.
AB  - PAP-1 is an in vitro phosphorylation target of the Pim-1 oncogene. Although PAP-1
      binds to Pim-1, it is not a substrate for phosphorylation by Pim-1 in vivo. PAP-1
      has recently been implicated as the defective gene in RP9, one type of autosomal
      dominant retinitis pigmentosa (adRP). However, RP9 is a rare disease and only two
      missense mutations have been described, so the report of a link between PAP-1 and
      RP9 was tentative. The precise cellular role of PAP-1 was also unknown at that
      time. We now report that PAP-1 localizes in nuclear speckles containing the
      splicing factor SC35 and interacts directly with another splicing factor, U2AF35.
      Furthermore, we used in vitro and in vivo splicing assays to show that PAP-1 has
      an activity, which alters the pattern of pre-mRNA splicing and that this activity
      is dependent on the phosphorylation state of PAP-1. We used the same splicing
      assay to examine the activities of two mutant forms of PAP-1 found in RP9
      patients. The results showed that while one of the mutations, H137L, had no
      effect on splicing activity compared with that of wild-type PAP-1, the other,
      D170G, resulted in both a defect in splicing activity and a decreased proportion
      of phosphorylated PAP-1. The D170G mutation may therefore cause RP by altering
      splicing of retinal genes through a decrease in PAP-1 phosphorylation. These
      results demonstrate that PAP-1 has a role in pre-mRNA splicing and, given that
      three other splicing factors have been implicated in adRP, this finding provides
      compelling further evidence that PAP-1 is indeed the RP9 gene.

PMID- 15474995
TI  - Oxidative stress and thioredoxin-interacting protein promote intravasation of
      melanoma cells.
AB  - Although intravasation may be a critical rate-limiting step in the metastatic
      cascade, the role of oxidative stress in intravasation is unknown. We tested the
      hypothesis that reactive oxygen species (ROS), regulated by thioredoxin
      interacting protein (Txnip) through the action of thioredoxin (Trx), influence
      human SK-MEL-28 melanoma cell reverse (basolateral-to-apical) transendothelial
      migration (TEM) in vitro as a model for intravasation. Reverse transendothelial
      migration was dose-dependently induced by hydrogen peroxide 2.4-fold for 0.1
      microM (P < 0.01) and 3.9-fold for 1 microM (P < 0.001) vs. control, and this
      effect was blocked by the antioxidant N-acetylcysteine. Overexpression of Txnip
      by infecting melanoma cells with adenovirus increased TEM 3-fold vs. control (P <
      0.001), and this increase was blocked by N-acetylcysteine, indicating a redox
      sensitive mechanism. Conversely, thioredoxin overexpression blocked hydrogen
      peroxide-induced TEM. Exposure to ultraviolet-A radiation increased ROS 1.8-fold
      (P < 0.01), and this was accompanied by a 45% reduction (P < 0.05) in thioredoxin
      activity and an 11.4-fold (P < 0.001) increase in Txnip gene expression. These
      data suggest that TEM of melanoma cells during intravasation is in part mediated
      by ROS-sensitive cellular signaling cascades, may be controlled by Txnip and its
      interaction with thioredoxin that in turn modulates cellular levels of oxidative
      stress, and may be initiated by ultraviolet-A induction of this cascade.

PMID- 15474996
TI  - Differential inside-out activation of beta2-integrins by leukotriene B4 and fMLP
      in human neutrophils.
AB  - We have investigated how LTB4, an endogenous chemoattractant encountered early in
      the inflammatory process, and fMLP, a bacteria-derived chemotactic peptide
      emanating from the site of infection, mediate inside-out regulation of the beta2
      integrin. The role of the two chemoattractants on beta2-integrin avidity was
      investigated by measuring their effect on beta2-integrin clustering and surface
      mobility, whereas their effect on beta2-integrin affinity was measured by the
      expression of a high affinity epitope, a ligand-binding domain on beta2
      integrins, and by integrin binding to s-ICAM. We find that the two
      chemoattractants modulate the beta2-integrin differently. LTB4 induces an
      increase in integrin clustering and surface mobility, but only a modest increase
      in integrin affinity. fMLP evokes a large increase in beta2-integrin affinity as
      well as in clustering and mobility. Lipoxin, which acts as a stop signal for the
      functions mediated by pro-inflammatory agents, was used as a tool for further
      examining the inside-out mechanisms. While LTB4-induced integrin clustering and
      mobility were inhibited by lipoxin, only a minor inhibition of fMLP-induced beta2
      integrin avidity and no inhibition of integrin affinity were detected. The
      different modes of the inside-out regulation of beta2-integrins suggest that
      distinct mechanisms are involved in the beta2-integrin modulation induced by
      various chemoattractants.

PMID- 15474997
TI  - Replication protein A and gamma-H2AX foci assembly is triggered by cellular
      response to DNA double-strand breaks.
AB  - Human replication protein A (RPA p34), a crucial component of diverse DNA
      excision repair pathways, is implicated in DNA double-strand break (DSB) repair.
      To evaluate its role in DSB repair, the intranuclear dynamics of RPA was
      investigated after DNA damage and replication blockage in human cells. Using two
      different agents [ionizing radiation (IR) and hydroxyurea (HU)] to generate DSBs,
      we found that RPA relocated into distinct nuclear foci and colocalized with a
      well-known DSB binding factor, gamma-H2AX, at the sites of DNA damage in a time
      dependent manner. Colocalization of RPA and gamma-H2AX foci peaked at 2 h after
      IR treatment and subsequently declined with increasing postrecovery times. The
      time course of RPA and gamma-H2AX foci association correlated well with the DSB
      repair activity detected by a neutral comet assay. A phosphatidylinositol-3 (PI
      3) kinase inhibitor, wortmannin, completely abolished both RPA and gamma-H2AX
      foci formation triggered by IR. Additionally, radiosensitive ataxia
      telangiectasia (AT) cells harboring mutations in ATM gene product were found to
      be deficient in RPA and gamma-H2AX colocalization after IR. Transfection of AT
      cells with ATM cDNA fully restored the association of RPA foci with gamma-H2AX
      illustrating the requirement of ATM gene product for this process. The exact
      coincidence of RPA and gamma-H2AX in response to HU specifically in S-phase cells
      supports their role in DNA replication checkpoint control. Depletion of RPA by
      small interfering RNA (SiRNA) substantially elevated the frequencies of IR
      induced micronuclei (MN) and apoptosis in human cells suggestive of a role for
      RPA in DSB repair. We propose that RPA in association with gamma-H2AX contributes
      to both DNA damage checkpoint control and repair in response to strand breaks and
      stalled replication forks in human cells.

PMID- 15474998
TI  - Gene expression profiling shows that macrophages derived from mouse embryonic
      stem cells is an improved in vitro model for studies of vascular disease.
AB  - Macrophages (Mphi) play an important role in the initiation and progress of the
      atherogenic process. They contribute to the growth of atherosclerotic plaque by
      affecting lipoprotein metabolism, matrix homeostasis, lipoprotein modification
      and cholesterol accumulation. Access to in vitro Mphi models is therefore
      important for understanding the mechanisms involved in the transition of the
      relatively simple fatty streak to more complex type of lesions. The aim of the
      present work was to compare the expression profile of macrophages differentiated
      from the hematopoietic lineage to peritoneal mouse macrophages and two commonly
      used mouse macrophage cell lines (J774.A1 and RAW264.7). Our results showed that
      the embryonic stem cell-derived macrophages (ES Mphi) had a more similar
      expression profile to peritoneal macrophages than the two mouse macrophage cell
      lines. The ES Mphi had unchanged expression of the majority of cholesterol efflux
      mediators when compared to mouse peritoneal macrophages, whereas the cell lines
      showed altered expression of several of these genes. A key gene in this process
      is apolipoprotein E, which is expressed in ES Mphi but not in macrophage cell
      lines. In conclusion, ES Mphi are likely to provide a better in vitro model than
      mouse Mphi cell lines to study macrophage involvement in atherosclerosis.

PMID- 15474999
TI  - Starvation for an essential amino acid induces apoptosis and oxidative stress in
      yeast.
AB  - Protracted starvation of auxotrophic Saccharomyces cerevisiae strains for an
      essential amino acid is commonly used to allow investigation of adaptive mutation
      mechanisms during starvation-induced cell cycle arrest. Under these conditions,
      the majority of cells dies during the first 6 days. We investigated starving
      cells for markers of programmed cell death and for the production of reactive
      oxygen species (ROS). We observed that protracted starvation for lysine or
      histidine resulted in an increasing number of cells exhibiting DNA fragmentation
      and chromatin condensation, thus an apoptotic phenotype. Not only respiration
      competent cells but also respiratory deficient rho0 cells were able to undergo
      programmed cell death. In addition the starving cells rapidly exhibited
      indicators of oxidative stress, independently of their respiratory competence.
      These results indicate that starvation for an essential amino acid results in
      severe cell stress, which may finally be the trigger of programmed cell death.

PMID- 15475000
TI  - GSK-3beta inhibition by lithium confers resistance to chemotherapy-induced
      apoptosis through the repression of CD95 (Fas/APO-1) expression.
AB  - Lithium exerts neuroprotective actions that involve the inhibition of glycogen
      synthase kinase-3beta (GSK-3beta). Otherwise, recent studies suggest that
      sustained GSK-3beta inhibition is a hallmark of tumorigenesis. In this context,
      the present study was undertaken to examine whether lithium modulated cancer cell
      sensitivity to apoptosis induced by chemotherapy agents. We observed that, in
      different human cancer cell lines, lithium significantly reduced etoposide- and
      camptothecin-induced apoptosis. In HepG2 cells, lithium repressed drug induction
      of CD95 expression and clustering at the cell surface as well as caspase-8
      activation. Lithium acted through deregulation of GSK-3beta signaling since (1)
      it provoked a rapid and sustained phosphorylation of GSK-3beta on the inhibitory
      serine 9 residue; (2) the GSK-3beta inhibitor SB-415286 mimicked lithium effects
      by repressing drug-induced apoptosis and CD95 membrane expression; and (3)
      lithium promoted the disruption of nuclear GSK-3beta/p53 complexes. Moreover, the
      overexpression of an inactivated GSK-3beta mutant counteracted the stimulatory
      effects of etoposide and camptothecin on a luciferase reporter plasmid driven by
      a p53-responsive sequence from the CD95 gene. In conclusion, we provide the first
      evidence that lithium confers resistance to apoptosis in cancer cells through GSK
      3beta inhibition and subsequent repression of CD95 gene expression. Our study
      also highlights the concerted action of GSK-3beta and p53 on CD95 gene
      expression.

PMID- 15475001
TI  - p18INK4c and p27KIP1 are required for cell cycle arrest of differentiated
      myotubes.
AB  - Myogenic differentiation is characterized by permanent and irreversible cell
      cycle withdrawal and increased resistance to apoptosis. These functions correlate
      with changes in expression and activity of several cyclin-dependent kinase
      inhibitors, including p18, p21, and p27. In this study, we examined the
      requirements for p18, p21, and p27 in initiating growth arrest in multinucleated
      myotubes under differentiation conditions and in maintaining terminal arrest upon
      restimulation of differentiated myotubes with mitogenic signals. Under
      differentiation conditions, only p27(-/-) or p18(-/-)p27(-/-) myotubes are
      capable of reentering the cell cycle and synthesizing DNA at a very low
      frequency. Escape from cell cycle arrest was significantly greater in p18(-/
      )p27(-/-) myotubes than in p27(-/-) myotubes. Stimulation of differentiated
      cultures with a mitogen-rich growth medium enhances p18(-/-)p27(-/-) myotube
      proliferation to encompass approximately half of the nuclei. p18(-/-)p21(-/-) and
      p21(-/-)p27(-/-) myotubes remain terminally arrested. Nuclei within individual
      restimulated p18(-/-)p27(-/-) myotubes can be found in all phases of the cell
      cycle, and a myotube can be multiphasic without any obvious deleterious effects.
      Increasing the time of differentiation or serum stimulation of p18(-/-)p27(-/-)
      myotubes neither increases the proliferation index of the myotube nuclei, nor
      does it alter the percentage of nuclei in each of the cell cycle phases. During
      the first 24 h of serum stimulation, the p18(-/-)p27(-/-) myotube nuclei that
      escape G0 arrest will rearrest in either S or G2 phase, without either mitosis or
      endoreplication. Apoptosis is increased in restimulated p18(-/-)p27(-/-) myotube
      nuclei, but is not specific for any cell cycle phase. These results suggest a
      collaborative role for p18 and p27 in initiating and maintaining G0 arrest during
      myogenic differentiation. While p18 and p27 appear to be essential in initiating
      G0 arrest in a proportion of postmitotic myotube nuclei, there must be another
      cell cycle inhibitor protein that functions with p18 and p27 in maintaining
      terminal arrest. We propose that the combined rate-limiting expressions of p18,
      p27, and this other inhibitor determine whether the myotube nuclei will remain
      postmitotic, or reenter the cell cycle, and if the nuclei escape G0 arrest, in
      which phase of the cell cycle the nuclei will ultimately rearrest.

PMID- 15475002
TI  - Macrophage migration inhibitory factor directly interacts with hepatopoietin and
      regulates the proliferation of hepatoma cell.
AB  - Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine involved
      in inflammation and immune responses as well as in growth factor-dependent cell
      proliferation, cell cycle, angiogenesis, and tumorigenesis. Several studies have
      documented MIF expression in the sera following hepatic resection or in the
      course of liver cancer progression, but there is a paucity of information
      regarding the effect of MIF on hepatoma cells and relating mechanisms. In this
      paper, by [3H] thymidine incorporation, we found that exogenously added MIF could
      promote the proliferation of HepG2 in a dose-dependent manner. Hepatopoietin
      (HPO), as a liver-specific regeneration augmenter, could be induced by the
      expression of MIF in hepatoma cells. The activity of HPO promoter was increased,
      and its levels were enhanced after MIF was overexpressed in hepatoma cells. The
      similarities between HPO and MIF in structure and action led us to investigate
      their interaction and the inducing biological significance. Using yeast two
      hybrid identification, we found that HPO interacted with MIF in yeast cells, and
      their binding ability was higher than that between HPO and JAB1 (Jun activation
      domain binding protein) or MIF and JAB1 in yeast cells. Their interaction was
      further verified by His pull-down assay in vitro and coimmunoprecipitation
      experiment in vivo. They were colocalized in the cytoplasm. Both HPO and MIF
      could bind to JAB1 and modulate the AP-1 pathway. When HPO and MIF were
      cotransfected into HepG2 cells, the binding activity of MIF to JAB1 was reduced,
      and the activity of AP-1 was improved. In contrast, MIF overexpressed in HepG2
      was unable to interfere with the binding activity of HPO to JAB1, but its
      potentiation on AP-1 activity was reduced significantly. Taken together, these
      results indicate that MIF plays an important role in the proliferation of
      hepatoma cells, and the effect of MIF is in concert with HPO.

PMID- 15475003
TI  - Direct interaction of Cbl with pTyr 1045 of the EGF receptor (EGFR) is required
      to sort the EGFR to lysosomes for degradation.
AB  - Mutation of the binding site for Cbl (Tyr1045) in the EGF receptor (EGFR) results
      in impaired ubiquitination but does not affect EGFR internalization. However, the
      Y1045F mutation resulted in strongly decreased degradation of the EGFR, as well
      as efficient recycling of EGFR to the plasma membrane. Significantly, more wild
      type EGFR than Y1045F EGFR was found localizing to multivesicular late endosomes.
      Ubiquitination of the EGFR was in HeLa cells inhibited both upon overexpressing
      the N-terminal part of Cbl and upon overexpressing a double mutant Grb2 incapable
      of interacting with Cbl and thereby being incapable of indirectly recruiting Cbl
      to the EGFR. Collectively, these data suggest that the ubiquitination resulting
      from direct binding of Cbl to pTyr1045 of the EGFR is critical for lysosomal
      sorting of the EGFR in contrast to ubiquitination resulting from Grb2-mediated
      binding of Cbl to the EGFR.

PMID- 15475004
TI  - Contribution of cellular contractility to spatial and temporal variations in
      cellular stiffness.
AB  - Scanning probe microscopy and immunofluorescence observations indicated that
      cellular stiffness was attributed to a contractile network structure consisting
      of stress fibers. We measured temporal variations in cellular stiffness when
      cellular contractility was regulated by dosing with lysophosphatidic acid or Y
      27632. This experiment revealed a clear relation between cellular stiffness and
      contractility: Increases in contractility caused cells to stiffen. On the other
      hand, decreases in contractility reduced cellular stiffness. In both cases, not
      only the stiffness of the stress fibers but also that of the whole of the cell
      varied. Immunofluorescence observations of myosin II and vinculin indicated that
      the stiffness variations induced by the regulation of cellular contractility were
      mainly due to rearrangements of the contractile actin network on the dorsal
      surface. Taken together, our findings provide evidence that the actin
      cytoskeletal network and its contractility features provide and modulate the
      mechanical stability of adherent cells.

PMID- 15475005
TI  - Runx2/Cbfa1 stimulates transdifferentiation of primary skeletal myoblasts into a
      mineralizing osteoblastic phenotype.
AB  - Runx2, a transcriptional activator downstream of bone morphogenetic protein (BMP)
      signaling, is essential to osteoblastic differentiation and bone formation and
      maintenance. BMPs activate complex signaling networks, utilizing numerous
      signaling molecules and transcription factors to induce expression of
      osteoblastic markers in mesenchymal cell types. However, the role of Runx2 in
      this process, particularly in an environment independent of the other regulatory
      elements modulated by BMPs, remains poorly understood. In the present study, we
      used retroviral gene delivery to examine the effects of sustained Runx2
      expression in primary myoblasts. Runx2 inhibited myogenesis, as demonstrated by
      suppression of MyoD and myogenin mRNA levels and reduced myotube formation.
      Additionally, Runx2-stimulated osteogenesis including osteoblastic gene
      expression, alkaline phosphatase activity, and biological mineral deposition.
      Notably, these osteogenic markers were induced to significantly greater levels
      than those observed in BMP-2-treated controls. These results demonstrate that
      direct exogenous expression of the Runx2 transcription factor, only one of
      numerous downstream targets of BMP signaling, is sufficient to induce
      transdifferentiation of myogenic cells into a mineralizing osteogenic lineage.
      This work underscores the potency of Runx2 as a regulator of osteogenesis and
      cell differentiation and provides new insights into the plasticity of committed
      mesenchymal cells.

PMID- 15475006
TI  - Signals from damaged but not undamaged skeletal muscle induce myogenic
      differentiation of rat bone-marrow-derived mesenchymal stem cells.
AB  - The regenerative capacity of skeletal muscle has been usually attributed to
      resident satellite cells, which, upon activation by local or distant stimuli,
      initiate a myogenic differentiation program. Although recent studies have
      revealed that bone-marrow-derived progenitor cells may also participate in
      regenerative myogenesis, the signals and mechanisms involved in this process have
      not been elucidated. This study was designed to investigate whether signals from
      injured rat skeletal muscle were competent to induce a program of myogenic
      differentiation in expanded cultures of rat bone-marrow-derived mesenchymal stem
      cells (MSC). We observed that the incubation of MSC with a conditioned medium
      prepared from chemically damaged but not undamaged muscle resulted in a time
      dependent change from fibroblast-like into elongated multinucleated cells, a
      transient increase in the number of MyoD positive cells, and the subsequent onset
      of myogenin, alpha-actinin, and myosin heavy chain expression. These results show
      that damaged rat skeletal muscle is endowed with the capacity to induce myogenic
      differentiation of bone-marrow-derived mesenchymal progenitors.

PMID- 15475007
TI  - P27 expression is regulated by separate signaling pathways, downstream of Ras, in
      each cell cycle phase.
AB  - The cyclin inhibitory protein p27Kip1 (p27) plays a vital role in regulating cell
      proliferation in response to the extracellular growth environment. Active
      proliferation requires the suppression of p27 levels throughout the cell cycle.
      Late in the cell cycle, p27 degradation requires phosphorylation of Thr 187 by
      cyclin dependent kinase 2, leading to recognition by the SCF ubiquitin ligase
      containing the Skp2 F-box protein. Suppression of p27 is also essential for cell
      proliferation early in the cell cycle, but this occurs independently of Skp2,
      whose expression is suppressed during G1 phase. In this study, we use a time
      lapse and quantitative imaging approach to study the connection between
      proliferative signaling and the degradation of p27 during each cell cycle period
      in actively cycling cells. Ras activity was required for the suppression of p27
      levels throughout the cell cycle, but separate pathways downstream of Ras
      signaling were required in different cell cycle periods. For example, inhibitors
      of MEK and phosphatidylinositol-3-kinase induced p27 expression primarily in G1
      phase, while inhibitors of AKT activity stimulated these levels primarily in S
      phase. Skp2 was expressed in a Ras-dependent manner at higher levels late in the
      cell cycle. Its ablation resulted in higher p27 levels primarily in G2 phase as
      expected. The fact that separate signaling pathways downstream of Ras function in
      each cell cycle phase to suppress p27 levels helps explain the vital connection
      between proliferative signaling, cell cycle control, and p27 expression.

PMID- 15475008
TI  - Calcium binding sequences in calmyrin regulates interaction with presenilin-2.
AB  - Calmyrin is a myristoylated calcium binding protein that contains four putative
      EF-hands. Calmyrin interacts with a number of proteins, including presenilin-2
      (PS2). However, the biophysical properties of calmyrin, and the molecular
      mechanisms that regulate its binding to different partners, are not well
      understood. By site-directed mutagenesis and Ca2+ binding studies, we found that
      calmyrin binds two Ca2+ ions with a dissociation constant of approximately 53
      microM, and that the two C-terminal EF-hands 3 and 4 bind calcium. Using
      ultraviolet spectroscopy, circular dichroism (CD), and NMR, we found that Ca(2+)
      free and -bound calmyrin have substantially different protein conformations. By
      yeast two-hybrid assays, we found that both EF-hands 3 and 4 of calmyrin must be
      intact for calmyrin to interact with PS2-loop sequences. Pulse-chase studies of
      HeLa cells transfected with calmyrin expression constructs indicated that wild
      type (Wt) calmyrin has a half-life of approximately 75 min, whereas a mutant
      defective in myristoylation turns over more rapidly (half-life of 35 min). By
      contrast, the half-lives of calmyrin mutants with a disrupted EF-hand 3 or EF
      hand 4 were 52 and 170 min, respectively. Using immunofluorescence staining of
      HeLa cells transfected with Wt and mutant calmyrin cDNAs, we found that both
      calcium binding and myristoylation are important for dynamic intracellular
      targeting of calmyrin. Double immunofluorescence microscopy indicated that Wt and
      myristoylation-defective calmyrin proteins colocalize efficiently and to the same
      extent with PS2, whereas calmyrin mutants defective in calcium binding display
      less colocalization with PS2. Our results suggest that calmyrin functions as a
      calcium sensor and that calcium binding sequences in calmyrin are important for
      interaction with the PS2 loop.

PMID- 15475009
TI  - Nox1 regulates apoptosis and potentially stimulates branching morphogenesis in
      sinusoidal endothelial cells.
AB  - Tubulogenic transformation of a nontubulogenic endothelial cell line NP31 by a
      constitutively activated form of the Flt-1 kinase (NP31/kinase) was accompanied
      by an increased expression of Nox1 by sixfold over NP31. Overexpression of Nox1
      in NP31 cells (NP31/Nox1) stimulated branching morphogenesis in Matrigel but
      surprisingly cords lacked a lumen. The branching morphogenesis by NP31/kinase and
      NP31/Nox1 cells was blocked either by N-acetyl-l-cysteine (NAC) or Tiron.
      Vascular endothelial growth factor (VEGF)-dependent sinusoidal endothelial cells
      (SEC) in primary culture showed fivefold increase in Nox1 expression 4 days after
      VEGF stimulation. Interestingly, VEGF-resistant apoptosis in SEC at day 7 was
      inhibited by NAC or by anti-Nox1 siRNA. These results suggest that Nox1 regulates
      apoptosis in SEC and can potentially stimulate branching morphogenesis in SEC
      derived NP 31 cells.

PMID- 15475010
TI  - Akt phosphorylation and NFkappaB activation are counterregulated under conditions
      of oxidative stress.
AB  - This study was designed to elucidate the mechanisms involved in elevated cell
      death arising from an altered endogenous oxidant state. Increased levels of cell
      death were detected in cells lacking Gpx1 following the addition of exogenous
      H2O2. This increased apoptosis correlated with a down-regulation in the
      activation of the PI(3)K-Akt survival pathway. The importance of this pathway in
      protecting against H2O2-induced cell death was highlighted by the increased
      susceptibility of wild-type cells to apoptosis when treated with the PI(3)K
      inhibitor, LY294002. Activation of the oxidative stress sensitive transcription
      factor, NFkappaB, was elevated in the Gpx1-/- cells. Significantly, NFkappaB
      activation could be increased in wild-type cells through the addition of dominant
      negative Akt. Therefore, our results suggest that the increased susceptibility of
      Gpx1-/- cells to H2O2-induced apoptosis can be attributed in part to diminished
      activation of Akt despite an up-regulation in the activation of the prosurvival
      NFkappaB. Thus, the PI(3)K-Akt and NFkappaB pathways can act independently of
      each other in an endogenous model of oxidative stress.

PMID- 15475011
TI  - Hydrogen peroxide mediates Rac1 activation of S6K1.
AB  - We previously reported that hydrogen peroxide (H2O2) mediates mitogen activation
      of ribosomal protein S6 kinase 1 (S6K1) which plays an important role in cell
      proliferation and growth. In this study, we investigated a possible role of H2O2
      as a molecular linker in Rac1 activation of S6K1. Overexpression of recombinant
      catalase in NIH-3T3 cells led to the drastic inhibition of H2O2 production by
      PDGF, which was accompanied by a decrease in S6K1 activity. Similarly, PDGF
      activation of S6K1 was significantly inhibited by transient transfection or
      stable transfection of the cells with a dominant-negative Rac1 (Rac1N17), while
      overexpression of constitutively active Rac1 (Rac1V12) in the cells led to an
      increase in basal activity of S6K1. In addition, stable transfection of Rat2
      cells with Rac1N17 dramatically attenuated the H2O2 production by PDGF as
      compared with that in the control cells. In contrast, Rat2 cells stably
      transfected with Rac1V12 produced high level of H2O2 in the absence of PDGF,
      comparable to that in the control cells stimulated with PDGF. More importantly,
      elimination of H2O2 produced in Rat2 cells overexpressing Rac1V12 inhibited the
      Rac1V12 activation of S6K1, indicating the possible role of H2O2 as a mediator in
      the activation of S6K1 by Rac1. However, H2O2 could be also produced via other
      pathway, which is independent of Rac1 or PI3K, because in Rat2 cells stably
      transfected with Rac1N17, H2O2 could be produced by arsenite, which has been
      shown to be a stimulator of H2O2 production. Taken together, these results
      suggest that H2O2 plays a pivotal role as a mediator in Rac1 activation of S6K1.

PMID- 15475012
TI  - Outcome assessment in aphasia: a survey.
AB  - There has been a marked increase in attention to the measurement of "outcomes"
      after speech-language intervention for adult aphasia. Consumers, speech-language
      pathologists (SLPs), and funding sources desire evidence of therapy outcomes that
      improve communication and enhance the quality of life for people with aphasia.
      While many assessment tools are available to measure outcomes after aphasia
      therapy, there is little information regarding the use of these tools in everyday
      practice by SLPs. Therefore, the current investigation was undertaken to identify
      and describe the practices of SLPs relative to outcome assessment in aphasia. An
      online survey of outcome assessment practices was distributed. Results revealed
      that 85% of the 94 respondents reportedly perform outcome assessment. A majority
      of respondents reported barriers to assessment such as time and funding
      limitations. Considerable variability existed in the types of assessments and the
      actual tools reported. The impact of the results on clinical practice is
      discussed. LEARNING OUTCOMES: As a result of this activity the reader will be
      able to (1) define outcome assessment in aphasia, (2) describe patterns of
      outcome assessment in aphasia as reported by survey respondents, and (3) describe
      a conceptual framework for situating outcome assessment in aphasia.

PMID- 15475013
TI  - The role of early language experience in the development of speech perception and
      phonological processing abilities: evidence from 5-year-olds with histories of
      otitis media with effusion and low socioeconomic status.
AB  - This study tested the hypothesis that early language experience facilitates the
      development of language-specific perceptual weighting strategies believed to be
      critical for accessing phonetic structure. In turn, that structure allows for
      efficient storage and retrieval of words in verbal working memory, which is
      necessary for sentence comprehension. Participants were forty-nine 5-year-olds,
      evenly distributed among four groups: those with chronic otitis media with
      effusion (OME), low socio-economic status (low-SES), both conditions (both), or
      neither condition (control). All children participated in tasks of speech
      perception and phonological awareness. Children in the control and OME groups
      participated in additional tasks examining verbal working memory, sentence
      comprehension, and temporal processing. The temporal-processing task tested the
      hypothesis that any deficits observed on the language-related tasks could be
      explained by temporal-processing deficits. Children in the three experimental
      groups demonstrated similar results to each other, but different from the control
      group for speech perception and phonological awareness. Children in the OME group
      differed from those in the control group on tasks involving verbal working memory
      and sentence comprehension, but not temporal processing. Overall these results
      supported the major hypothesis explored, but failed to support the hypothesis
      that language problems are explained to any extent by temporal-processing
      problems. LEARNING OUTCOMES: As a result of this activity, the participant will
      be able to (1) Explain the relation between language experience and the
      development of mature speech perception strategies, phonological awareness,
      verbal working memory, and syntactic comprehension. (2) Name at least three
      populations of individuals who exhibit delays in the development of mature speech
      perception strategies, phonological awareness, verbal working memory, and
      syntactic comprehension, and explain why these delays exist for each group. (3)
      Point out why perceptual strategies for speech are different for different
      languages. (4) Describe Baddeley's model [A.D. Baddeley, The development of the
      concept of working memory: implications and contributions of neuropsychology, in:
      G. Vallar, T. Shallice (Eds.), Neuropsychological Impairments of Short-term
      Memory, Cambridge University Press, New York, 1990, p. 54] of verbal working
      memory.

PMID- 15475014
TI  - Low intensity phonological awareness training in a preschool classroom for
      children with communication impairments.
AB  - Phonological awareness is a term that refers to one's knowledge of the sound
      structure of spoken language. Children who understand that sounds in language
      represent the letters used in reading and writing typically learn to read more
      easily than children who do not. Children with language and/or speech impairments
      often demonstrate a lack of phonological awareness. Thus, it is important to
      identify problems in phonological awareness and to implement intervention
      programs early. The purpose of this study was to determine if a low intensity,
      classroom phonological awareness program improved phonological awareness skills
      for preschool children with language and/or speech impairments. Results suggested
      that children made significant gains in phonological awareness after
      participating in the intervention. LEARNING OUTCOMES: As a result of this
      activity, the reader will be able to: (1) identify components of phonological
      awareness program; (2) evaluate effectiveness of phonological awareness
      intervention.

PMID- 15475015
TI  - The combined use of cholesterol-lowering drugs and cholesterol-lowering bread
      spreads: health behavior data from Finland.
AB  - BACKGROUND: Cholesterol-lowering drugs may metabolically interact with
      cholesterol-lowering bread spreads. This study analyses the prevalence of use of
      drugs, bread spreads or the combination of both in people aware of their
      high/elevated cholesterol level, and compares users of the three therapies on
      health behavior and demographics. METHODS: Participants (9581, 25-74 years) from
      The National FINRISK 2002 Study filled out a questionnaire on demographics and
      health (related) issues. Blood samples, blood pressure, body weight and height
      were measured. RESULTS: Of those who reported to have a high cholesterol level
      (31% of the study population), 19% used cholesterol-lowering drugs, 11% used
      cholesterol-lowering bread spreads and 5% combined both therapies. On a
      population level, only 1% jointly used a drug and bread spread therapy. The
      combination was used by especially highly educated people and those having a
      healthy diet. CONCLUSION: Combining a cholesterol-lowering drug with a bread
      spread regimen is relatively rare, even among those being aware of their high
      cholesterol levels. The combined usage was most frequent among 'the better off'.
      Public health risks of a metabolic interaction between both therapies may not be
      of major importance yet, but future follow-up is recommended.

PMID- 15475016
TI  - Expenditures associated with preventive healthcare.
AB  - BACKGROUND: The Office of Disease Prevention and Health Promotion emphasizes the
      use of preventive healthcare interventions to "increase quality and years of
      healthy life". The objective of this study is to evaluate over a 1-year period
      the total individual healthcare expenditures based upon the likelihood of the
      person utilizing preventive healthcare measures. METHODS: We analyzed data from
      the 1998 Medical Expenditure Panel Survey (MEPS) to compare healthcare
      expenditures of respondents who have and have not followed generally accepted
      preventive healthcare measures including influenza vaccination, blood pressure
      checkup, prostate examination, cholesterol determination, and mammography.
      RESULTS: In general, respondents who lacked evidence of pursuing accepted
      preventive healthcare practices had lower overall healthcare expenditures in 1998
      compared to those who pursued such practices. Specifically, they had lower
      expenditures for office-based visits and for prescriptions. CONCLUSIONS: People
      who pursue accepted preventive healthcare measures spent more for their total
      healthcare over a given year.

PMID- 15475017
TI  - Decline in smoking cessation rate associated with high self-efficacy scores.
AB  - BACKGROUND: Clinical observation indicates that self-efficacy, although generally
      linked with maintaining smoking cessation, can be excessive. METHODS: In the
      present study, this phenomenon was explicitly investigated by adding the squared
      component of self-efficacy to the logistic regression analyses for a treatment
      sample (n = 381) to predict long-term success. RESULTS: Quitters with very high
      posttreatment self-efficacy were found to be at a greater risk for unsuccessful
      smoking cessation than quitters with merely high posttreatment self-efficacy, and
      by accounting for this phenomenon, long-term success was better predicted. No
      such relation was found for self-efficacy change. CONCLUSIONS: It is possible
      that quitters with very high levels of self-efficacy overestimate their capacity
      to quit and thereby neglect the use of coping skills and possibly engage in more
      high-risk situations.

PMID- 15475018
TI  - Proximity of supermarkets is positively associated with diet quality index for
      pregnancy.
AB  - OBJECTIVES: To investigate the association between distance to the closest
      supermarket and a composite measure of diet, the diet quality index for pregnancy
      (DQI-P) was constructed. METHODS: Data from the Pregnancy, Infection and
      Nutrition (PIN) cohort, a prospective study of determinants of preterm birth,
      were analyzed. Food frequency questionnaires were used to construct DQI-P which
      includes: servings of grains, vegetables, fruits, folate, iron and calcium
      intake, percentage of calories from fat, and meal pattern score. Street address
      of residence, supermarkets, grocery and convenience stores were geocoded.
      Participants with complete food frequency and address data were included (n =
      918). Multinomial logistic regression was used to estimate the conditional
      association of food outlets on diet quality, controlling for confounders and
      using a robust variance estimator to account for clustering of neighborhood
      characteristics. RESULTS: Women living greater than 4 miles from a supermarket
      were more than twice the odds (adjusted odds ratio = 2.16; 95% confidence
      interval = 1.2, 4.0) of falling into the lowest compared to highest DQI-P tertile
      compared to women living within 2 miles of a supermarket, after controlling for
      individual characteristics, other food retail outlets. CONCLUSION: These findings
      suggest that proximity of food retail outlets influences the diet quality of
      pregnant women.

PMID- 15475019
TI  - Violent crime and outdoor physical activity among inner-city youth.
AB  - BACKGROUND: Previous studies have shown poor correlation between subjective
      assessments of neighborhood safety and physical activity. This study was
      performed to model relationships between adolescents' outdoor physical activity
      and objectively measured violent crime densities, along with other key
      environmental variables. METHODS: Participants' physical activity was measured
      using a validated questionnaire. Multiple regression analysis was performed using
      outdoor physical activity away from school (OPA) as the dependent variable.
      Environmental factors included the density of violent crime within 1/2 mi of each
      participant's home, distance to nearest open play space, per capita income, and
      participants' subjective assessment of neighborhood safety. RESULTS: Multiple
      regression analysis showed that distance to nearest open play space was inversely
      and significantly associated with boys' OPA, while density of violent crime
      within 1/2 mi of home was inversely and significantly associated with girls' OPA.
      Girls' perceptions that their neighborhood was safe for physical activity were
      also associated with higher levels of OPA, while boys' assessments of
      neighborhood safety were not significantly related to OPA. CONCLUSIONS:
      Neighborhood violent crime may be a significant environmental barrier to outdoor
      physical activity for urban dwelling Mexican-American adolescent girls. Future
      studies of physical activity and the environment should use objective measures of
      environmental factors.

PMID- 15475020
TI  - Contrasting mediating variables in two 5-a-day nutrition intervention programs.
AB  - BACKGROUND: Researchers have advocated mediational analysis for behavioral
      intervention studies to link the supporting theory used in an intervention with
      the mediating variables and with its ultimate success or failure. Few mediational
      analyses have been reported for school-based nutrition studies. The conduct of
      mediational analyses within multi-site studies may provide advantages for the
      standardization of methods and for the replication and generalizability of
      findings. METHODS: This study identified mediators of two school-based nutrition
      interventions for 4th graders. Three variables were tested on the four criteria
      necessary to establish mediation of intervention effects on changes in fruit and
      vegetable consumption (FVC) in 4th graders (Alabama, N = 1584; Minnesota, N =
      522). FVC was measured in children using 24-h dietary recalls. Mediators were
      assessed using questionnaires completed by children and parents. RESULTS: All
      criteria were met in Alabama for a single-item measure of knowledge of the 5-a
      day daily consumption guideline. Knowledge and parent consumption satisfied one
      criterion in Minnesota. Knowledge accounted for 9.78% of the total intervention
      effect in Alabama. CONCLUSIONS: Knowledge of the 5-a-day guideline for fruit and
      vegetable consumption may mediate intervention effects. Future work should
      include tests of mediational models in multi-site studies.

PMID- 15475021
TI  - Effects of exercise on emerging and traditional cardiovascular risk factors.
AB  - BACKGROUND: Common cardiovascular disease risk factors (e.g., insulin and aerobic
      fitness) are improved with exercise; however, few studies have addressed the
      potential for training to modify emerging cardiovascular disease risk factors
      such as homocysteine and high-sensitivity C-reactive protein. METHODS: Sedentary
      adults (n = 324, 48.9 +/- 8.4 years) were randomized to four groups differing in
      training intensity (moderate = 45-55% or high = 65-75% of heart rate reserve) and
      frequency (low = 3-4, 30-min sessions/week or high = 5-7, 30 min-sessions/week).
      RESULTS: Within-group changes in homocysteine, insulin, and aerobic fitness were
      significant (all P < 0.0125). Furthermore, homocysteine increased in the high
      intensity-low-frequency (0.98 +/- 2.32 micromol/L) and high-intensity-high
      frequency (0.93 +/- 2.56 micromol/L) groups, while aerobic fitness increased in
      the moderate-intensity-high-frequency (0.99 +/- 2.01 mL min(-1) kg(-1)) and high
      intensity-high-frequency (1.77 +/- 2.97 mL min(-1) kg(-1)) groups (all P <
      0.003). The change in aerobic fitness was greater in the high-intensity-high
      frequency compared to the moderate-intensity-low-frequency group (1.77 +/- 2.97
      vs. 0.36 +/- 2.10 mL min(-1) kg(-1), P = 0.0014) (effect size estimate = 0.60 mL
      min(-1) kg(-1)). The main effects for intensity, with respect to the change in
      insulin (effect size estimate = 0.46 microU/mL), and frequency, with respect to
      the change in aerobic fitness (effect size estimate = 0.38 mL min(-1) kg(-1)),
      were significant (P < 0.0125). CONCLUSION: Although frequent bouts of higher
      intensity exercise were particularly effective in reducing fasting insulin and
      improving fitness, they resulted in slightly increased homocysteine levels.

PMID- 15475022
TI  - Awareness and use of community walking trails.
AB  - BACKGROUND: Community trail development is an emerging strategy to increase
      physical activity (PA) among community residents. The purpose of this study was
      to assess awareness and use of trails and compare perceptions to objective data.
      METHODS: A telephone survey was administered to a stratified sample of adults (N
      = 1,112) in a southeastern county in the United States. Respondents' home
      addresses and the locations of trails were entered into a GIS database. A kappa
      statistic was used to measure agreement between awareness and presence of trails.
      Differences in reported trail use patterns by sex, race, education, and PA levels
      were evaluated. RESULTS: There was no agreement between the awareness and
      presence of trails (kappa = 0.07). Fifty-six percent of the respondents reported
      having trails; however, only 33% reported using the trails. Of the trail users,
      42% reported being regularly active in moderate-to-vigorous PA (30+ min/day for
      5+ days/week), and 51% reported being less active (P < 0.003). Among walkers (>
      or =30 min/day for > or =5 days/week), 49% of regular walkers and 35% of
      irregular walkers (< walkers) reported using the trails (P < 0.04). CONCLUSIONS:
      Awareness of existing trails in this community and levels of use were low.
      Marketing programs should promote awareness and use of trails among older adults
      and irregularly active adults.

PMID- 15475023
TI  - Assessing the reliability and validity of anti-tobacco attitudes/beliefs in the
      context of a campaign strategy.
AB  - OBJECTIVES: To identify multi-item attitude/belief scales associated with the
      theoretical foundations of an anti-tobacco counter-marketing campaign and assess
      their reliability and validity. METHODS: The data analyzed are from two state
      wide, random, cross-sectional telephone surveys [n(S1)=1,079, n(S2)=1,150]. Items
      forming attitude/belief scales are identified using factor analysis. Reliability
      is assessed with Chronbach's alpha. Relationships among scales are explored using
      Pearson correlation. Validity is assessed by testing associations derived from
      the Centers for Disease Control and Prevention's (CDC) logic model for tobacco
      control program development and evaluation linking media exposure to
      attitudes/beliefs, and attitudes/beliefs to smoking-related behaviors. Adjusted
      odds ratios are employed for these analyses. RESULTS: Three factors emerged:
      traditional attitudes/beliefs about tobacco and tobacco use, tobacco industry
      manipulation and anti-tobacco empowerment. Reliability coefficients are in the
      range of 0.70 and vary little between age groups. The factors are correlated with
      one-another as hypothesized. Associations between media exposure and the
      attitude/belief scales and between these scales and behaviors are consistent with
      the CDC logic model. CONCLUSIONS: Using reliable, valid multi-item scales is
      theoretically and methodologically more sound than employing single-item measures
      of attitudes/beliefs. Methodological, theoretical and practical implications are
      discussed.

PMID- 15475024
TI  - Trends in educational inequalities in smoking in northern, mid and southern
      Italy, 1980-2000.
AB  - BACKGROUND: We aimed to determine the direction and magnitude of socioeconomic
      inequality in smoking in Italy over the last two decades, focusing on both
      national and macro-regional patterns. METHODS: We used data from six National
      Health Interview Surveys from 1980 to 2000, whose sample size ranged between
      60,000 and 140,000. We calculated age-adjusted prevalence rates of current
      smoking and estimated odds ratios (OR) and relative indexes of inequality (with
      95% confidence intervals) using logistic regression analysis. RESULTS: In men
      aged 25-49, the OR of current smoking of low compared to high educated was 1.26
      (95% CI: 1.16, 1.37) in 1980 and 1.71 (95% CI: 1.62, 1.80) in 2000. A reversal of
      the association between education and tobacco use from positive (OR = 0.43) to
      negative (OR = 1.12) was found for women of the same age group. Changes in
      educational inequalities in smoking were similar between different macro-regions
      for men, whereas among women, smaller differentials over all the study period
      were found in southern regions compared to central and northern regions, despite
      similar direction in trends. CONCLUSIONS: The gap between high- and low-educated
      groups has widened, especially in the youngest generations. Southern regions lag
      behind central and northern Italy in the progression of the smoking epidemic.

PMID- 15475025
TI  - eNOS Glu298Asp polymorphism and hypertension in a cohort study in Japanese.
AB  - BACKGROUND: Some recent case-control association studies have suggested negative
      and positive relationship between Glu298Asp (the substitution of aspartic acid
      for glutamic acid at amino acid position 298) polymorphism of the endothelial
      nitric oxide synthase (eNOS) gene and hypertension. To investigate whether the
      Glu298Asp polymorphism of the eNOS gene affects the incidence of hypertension, a
      retrospective cohort study was performed. METHODS: The baseline data among
      Japanese workers in Shimane Prefecture, Japan, were obtained at regular health
      examination in 1992, and a retrospective cohort study was performed to analyze
      the influence of Glu298Asp polymorphism on the incidence of hypertension in 1998.
      RESULTS: The incidences of Glu298Glu, Glu298Asp, and Asp298Asp genotypes in the
      subjects were 86.4%, 12.6% and 1.1%, respectively. The risk ratios of Glu298Asp
      and Asp298Asp against Glu298Glu for the incidence of hypertension by single
      variance analysis were 0.830 in total subjects [95% confidence interval (CI)
      0.474-1.452], 0.596 in subjects 20-39 years old (95% CI; 0.207-1.717), and 0.915
      in subjects 40-59 years old (95% CI; 0.464-1.805). The risk ratios of Glu298Asp
      and Asp298Asp against Glu298Glu for the incidence of hypertension by multiple
      variance analysis adjusted for sex, BMI, serum total cholesterol, serum high
      density lipoprotein (HDL) cholesterol, fasting glucose, cigarette smoking,
      drinking habits, eating habits, and exercise in 1992 were 0.750 in total subjects
      (95% CI; 0.421-1.335), 0.505 in subjects 20-39 years old (95% CI; 0.170-1.496),
      and 0.873 in subjects 40-59 years old (95% CI; 0.434-1.757). CONCLUSION: These
      results suggested no association between the Glu298Asp gene polymorphism and the
      incidence of hypertension in this selected population.

PMID- 15475026
TI  - Determinants of supplement usage.
AB  - BACKGROUND: As the use of supplements is growing, this study examines the
      determinants of vitamin and herbal supplement usage. Instead of treating these as
      all-encompassing categories, they are broken into specific vitamins and herbs and
      compared to see if users are different. A measure of frequency of vitamin use is
      also created. METHODS: Logistic and ordinal logistic regressions are run on a
      sample of 24,834 from the National Health Interview Survey (NHIS) 2000. RESULTS:
      Women are generally more likely to use supplements than men. Non-Latino Whites
      are generally more likely to use supplements than non-Latino Blacks and Mexicans.
      However, despite these general trends, it proves fruitful to break up supplement
      use into smaller categories. The data provide some evidence that determinants
      vary by particular supplement. However, including a measure of frequency does not
      change the picture much. CONCLUSIONS: Considering this, more information is
      needed on why people use particular supplements and what their sources of
      information are.

PMID- 15475027
TI  - Smoking topography and trajectory of asthmatic adolescents requesting cessation
      treatment.
AB  - BACKGROUND: Teenage smokers cite health concerns as their primary motivators for
      tobacco smoking cessation. Smoke exposure aggravates the clinical course of
      asthma, yet few reports have examined the association between asthma and smoking
      topography and trajectory. METHODS: Before their enrollment in a smoking
      cessation trial, we assessed the smoking topography (i.e., puff volume, maximum
      puff velocity, puff duration, and interpuff interval) and smoking trajectory
      (i.e., age of first cigarette, age of daily smoking, time to treatment request,
      and prior quit attempts) in 30 self-reported asthmatic and 92 nonasthmatic
      tobacco-dependent teenagers (mean age, 15.2 +/- 1.3 years, 28.7% African
      American). Approximately one-half of asthmatics used prescribed medications for
      their asthma. RESULTS: There was no significant difference in smoking topography
      or smoking trajectory variables between asthmatic and nonasthmatic adolescents,
      nor between medicated and nonmedicated asthma subgroups. CONCLUSIONS: Although
      tobacco smoking exacerbates asthmatic symptoms, these data suggest that age of
      smoking initiation, as well as smoking topography characteristics in asthmatic
      adolescents, does not differ from those of adolescents without asthma. These
      findings highlight the need for more effective health counseling of asthmatic
      youth regarding the physical and behavioral effects of smoking.

PMID- 15475028
TI  - The role of health insurance on Pap smear and mammography utilization by
      immigrants living in the United States.
AB  - BACKGROUND: Nearly half of recent immigrants to the United States lack health
      insurance. Access to cancer screening services for this group is problematic. We
      examine the role of health insurance and having a usual source of care (USC) on
      Pap smear and mammography utilization by immigrant women using a nationally
      representative sample. METHODS: We used a telephone survey that oversampled
      racial and ethnic minorities. We analyzed data on 3,622 women age 18-70. We
      classified the 822 foreign-born women as recent immigrants if they had resided in
      the United States for under 10 years; LT immigrants were those with a longer
      tenure. RESULTS: Among recent immigrants, 73% and 78% (SE 4%) reported a Pap
      smear or mammogram, respectively, in the previous 2 years versus 89% and 89% of
      U.S.-born women (P < 0.05 for both comparisons). Among those with insurance or a
      USC, differences in screening between recent immigrants and U.S.-born women were
      four percentage points or less and not statistically significant. However,
      uninsured recent immigrants were less likely than uninsured U.S.-born women to
      have Pap smears [60% (SE 7%) versus 71%, P < 0.05]. Adjusting for differences in
      sociodemographics, health attitudes or beliefs, patient or provider
      communication, and the medical care environment, insurance remained the strongest
      predictor of screening. CONCLUSION: Disparities in screening were greatly
      attenuated among the insured population. Increasing awareness of available safety
      net sources of care may also improve cancer screening among uninsured recent
      immigrants.

PMID- 15475029
TI  - Parental factors and adolescents' smoking behavior: an extension of The theory of
      planned behavior.
AB  - BACKGROUND: The aim of the present study is to investigate whether general
      parenting factors (i.e., quality parent-child relationship, psychological
      control, strict control, parental knowledge) and parental smoking add to The
      theory of planned behaviour [Organ Behav. Hum. Dec. 50 (1991) 179] in predicting
      the onset of smoking. A mediation model is applied in which parental factors
      affect smoking behavior indirectly by affecting smoking cognitions (i.e.,
      attitude, self-efficacy, and social norm). METHODS: The model was tested in a
      longitudinal study on 1,070 adolescents, aged 10-14 years old. Structural
      equation models (SEM) on current and on future smoking behavior were tested.
      RESULTS: The findings showed that the quality of the parent-child relationship
      and parental knowledge affected adolescents' smoking behavior indirectly, while
      parental smoking behavior had a direct effect. Strict control and psychological
      control were found to be unrelated to adolescents' smoking onset. CONCLUSIONS: In
      prevention campaigns, parents should be informed of the extent to which they
      exert influence on their child's smoking behavior and should be given advice and
      information on how they can prevent their children from starting to smoke.

PMID- 15475030
TI  - Administering an effective health intervention for smoking cessation online: the
      international users of Stop-Tabac.
AB  - BACKGROUND: The Internet has opened up new possibilities in public health, yet to
      date, there are few examples of online health interventions that go beyond
      information provision. This paper describes the users and return rates of an
      effective intervention for smoking cessation that has gone online. METHODS: Open
      enrollment of smokers via links and search engines with voluntary follow-up for
      an Internet-based expert system in French and English. RESULTS: Between June 1998
      and March 2001, 18,361 people from 112 countries used the program. When compared
      to the distribution of smokers in the general population in seven main countries,
      smokers in the action stage (11%) were overrepresented among online program
      users. Among the 3591 returnees in the study period (20%), we observed a median
      time to return of 132.5 days. One of the strongest predictors of return was stage
      of change with smokers in the action stage being most likely to return (28%) and
      those in the precontemplation stage least likely (14%). CONCLUSIONS: The reach of
      an online public health intervention can be impressive in geographical and
      numerical terms. Although the quality of behavioral data collected was high, the
      utility of this medium for science should be refined.

PMID- 15475031
TI  - Web-based screening and brief intervention for the spectrum of alcohol problems.
AB  - CONTEXT: Many persons who drink excessively remain unidentified and do not
      receive interventions. Screening and intervention using the World Wide Web could
      make such services more accessible and therefore more widely used. OBJECTIVE: To
      evaluate the use of a novel alcohol screening and brief intervention Web site.
      DESIGN: A Web site was developed, posted, and its use was evaluated. We analyzed
      a sample of visitors who completed alcohol screening over a 14-month period to
      describe their alcohol use, and their use of portions of the Web site that
      provide information and referral resources. SETTING: The Internet. PATIENTS OR
      OTHER PARTICIPANTS: Web site visitors, with a focus on visitors who completed an
      alcohol-screening questionnaire about their own drinking. INTERVENTION: Brief
      intervention via the Web site, consisting mainly of feedback, advice, and a menu
      of change options and referral information. MAIN OUTCOME MEASURES: Self-reported
      drinking amounts and alcohol screening test scores, and utilization of Web site
      components. RESULTS: Visitors completed online alcohol screening questionnaires
      at a rate of 50,711/year of 115,925 visitors/year. In a 14-month period, 39,842
      adults completed the questionnaire about their own drinking habits; 66% were men,
      90% reported drinking hazardous amounts (per occasion or typical weekly amounts),
      88% reported binge (per occasion) drinking, and 55% reported typically exceeding
      weekly risky drinking limits. Most (65%) had alcohol screening test results
      (AUDIT > or = 8) consistent with alcohol abuse or dependence; similar proportions
      of women and men were hazardous drinkers. One-fifth of visitors visited portions
      of the Web site that provided additional information about alcohol use and
      referrals. Visitors with possible alcohol abuse or dependence were more likely
      than those without these disorders to visit a part of the Web site designed for
      those seeking additional help (33% vs. 8%, P < 0.0001). CONCLUSIONS: A well
      publicized, easily accessible, research-based screening and intervention Web site
      can attract many users, most of whom are drinking excessively, and many of whom
      avail themselves of referral information after receiving individualized feedback.

PMID- 15475032
TI  - Antecedents and outcomes of marijuana use initiation during adolescence.
AB  - BACKGROUND: This study identified similarities and differences in risk factors
      for marijuana use initiation from grades 7 to 8, grades 8 to 9, and grades 9 to
      10, and examined differences between earlier initiates, later initiates, and
      nonusers on various problem behaviors at grade 10. METHOD: Longitudinal data were
      used to examine predictors and outcomes associated with marijuana initiation from
      grade 7 (N = 1,955) to grade 10 (N = 909). Participants completed yearly surveys
      to assess problem behaviors, social influences, and marijuana-related attitudes
      and behavior. RESULTS: Earlier initiates were more likely than later initiates to
      exhibit problem-related marijuana use, hard drug use, polydrug use, poor grades,
      and low academic intentions at grade 10. Across ages, initiation was predicted by
      smoking, frequency of marijuana offers, and poor grades. Results provided some
      evidence for a shift from familial to peer influence on marijuana initiation with
      increasing age. Marijuana-related beliefs were relatively weak predictors of
      initiation at all ages after controlling for pro-marijuana social influences and
      engagement in other types of substance use and delinquent behavior. CONCLUSIONS:
      Results emphasize the importance of early intervention and identify a wide range
      of potentially modifiable risk factors that may be targeted.

PMID- 15475034
TI  - Attitudes, subjective norms and perception of behavioural control as predictors
      of sun-related behaviour in Swedish adults.
AB  - BACKGROUND: Exposure to ultraviolet (UV) radiation is the major preventable cause
      of skin cancer. The aim of this study was to investigate the explanatory value of
      attitudes, subjective norms and perceived behavioural control on behaviours
      related to UV exposure. METHOD: A random population-based sample (n = 1752, 18-37
      years of age) in the Stockholm County, Sweden, answered a questionnaire with
      items on sun related behaviours and beliefs. The items concerned issues
      influenced by the Theory of Planned Behaviour, that is, attitudes, subjective
      norms and perceived behavioural control. Logistic regression analysis was used to
      examine the associations between behaviours and beliefs. RESULTS: Positive
      attitudes towards being tanned and being in the sun were both strongly associated
      with time spent in the sun, intentional tanning, sunbed use, going on vacation to
      a sunny resort, intention to decrease sunbathing and use of protection against
      the sun. Perceiving sunbathing as risky was associated with using different ways
      to protect and intending to reduce sun exposure. Having people around oneself who
      frequently sunbathe was related to intentional tanning and vacations to sunny
      resorts. Finally, perceived behavioural control was associated with use of
      sunscreen and use of other ways to protect from the sun among women. CONCLUSION:
      The study identified factors on which primary preventive interventions towards
      decreasing sun exposure should be focused.

PMID- 15475033
TI  - Inhibiting progression of coronary calcification using Aged Garlic Extract in
      patients receiving statin therapy: a preliminary study.
AB  - BACKGROUND: Aged Garlic Extract (AGE) reduces multiple cardiovascular risk
      factors, including blood pressure, cholesterol, platelet aggregation and
      adhesion, while stimulating nitric oxide generation in endothelial cells.
      However, no study has evaluated the ability of AGE to inhibit vascular
      calcification, a marker of plaque formation in human coronary arteries.
      OBJECTIVE: To assess the efficacy of Aged Garlic Extract (AGE) on changing the
      rate of atherosclerosis progression as compared to placebo. DESIGN: A placebo
      controlled, double-blind, randomized pilot study to determine whether the
      atherosclerotic plaque burden detected by electron beam tomography (EBT) will
      change at a different rate under the influence of AGE as compared to placebo.
      Twenty-three patients were enrolled, and 19 patients completed the study
      protocol. AGE 4 ml or the equivalent amount of placebo was given to subjects.
      Duration of the study was 1 year. S-allylcysteine (SAC), one of the active
      compound of AGE, was measured in the blood as a compliance marker. RESULTS: The
      mean change of the calcium score (volumetric method) for the AGE group (n = 9)
      was 7.5 +/- 9.4% over 1 year. The placebo group (n = 10) demonstrated an average
      increase in calcium scores of 22.2 +/- 18.5%, significantly greater than the
      treated cohort (P = 0.046). There were no significant differences in individual
      cholesterol parameters or C reactive protein between the groups. In patients
      randomized to AGE, there was a nonsignificant trend for improving
      cholesterol/high-density lipoprotein ratio (P = 0.07) and homocysteine level (P =
      0.08). CONCLUSIONS: This small pilot study indicates the potential ability of AGE
      to inhibit the rate of progression of coronary calcification, as compared to
      placebo over 1 year. Should these findings be extended and confirmed in larger
      studies, garlic may prove useful for patients who are at high risk of future
      cardiovascular events.

PMID- 15475035
TI  - The use of patient and physician reminders for preventive services: results from
      a National Study of Physician Organizations.
AB  - BACKGROUND: Clinical preventive services improve patient health, and reminder
      systems can increase the use of such services. However, physician organizations
      often underutilize clinical preventive service reminders. Little is known about
      the incentives, capabilities, and organizational characteristics associated with
      the use of reminders by physician organizations. METHODS: The predictors of
      patient and physician reminder system use were examined in a sample of 1,104 US
      physician organizations. The cross-sectional sample was obtained through a
      telephone survey with a 70% response rate. RESULTS: Fifty-one percent of
      physician organizations used mammogram reminders, 41% used influenza immunization
      reminders, and 26% used eye exam reminders for patients. Eighteen percent of
      physician organizations used computer-generated reminders to physicians. Required
      reporting of data (P = 0.0006), public recognition for quality (P = 0.0002), and
      IT capabilities (P < 0.0001) were strongly associated with patient reminder use.
      Medical groups were more likely to use patient-level reminders than independent
      practice associations (IPAs) (P < 0.0001). Physician reminder use was related to
      required reporting of data (P < 0.0001) and IT capabilities (P < 0.0001).
      CONCLUSIONS: Physician organizations have relatively low use of preventive
      service reminders to patients and physicians. Offering quality incentives to
      physician organizations and improving their IT capabilities may increase the use
      of preventive service reminders and improve the delivery of preventive care.

PMID- 15475036
TI  - Longitudinal predictors of serious physical and sexual dating violence
      victimization during adolescence.
AB  - BACKGROUND: This study identifies potentially modifiable risk factors for the
      onset of and chronic victimization from serious physical and sexual dating
      violence. METHODS: One thousand two hundred ninety-one 8th and 9th graders from a
      county in North Carolina were assessed annually for 5 and 4 years, respectively.
      RESULTS: For males, having been hit by an adult with the intention of harm,
      having low self-esteem, and having been in a physical fight with a peer predicted
      onset of serious physical dating violence victimization. Those variables, plus
      having a friend who has been a victim of dating violence, alcohol use, and being
      white, predicted chronic victimization for males. For females, onset of serious
      physical dating violence victimization was predicted by having been hit by an
      adult; that variable, plus living in a single-parent household, predicted chronic
      victimization from serious physical violence. Also for females, onset of sexual
      violence victimization was predicted by having a friend who has been the victim
      of dating violence and being depressed; those variables and gender stereotyping
      predicted chronic victimization from sexual dating violence. CONCLUSIONS: The
      findings identify high-risk groups and risk factors to target for intervention
      and have implications for approaches to delivering dating violence prevention
      programs.

PMID- 15475037
TI  - Psychosocial variables in a cohort of students in grades 8 and 11: a comparison
      of current and never smokers.
AB  - BACKGROUND: Specific hypotheses regarding putative mechanisms by which stressful
      life events might be related to smoking initiation among adolescents have been
      tested cross-sectionally on a cohort of 1598 grade 6 students in Scarborough,
      Canada. The purpose of this study was to examine the utility of these cross
      sectional models in accounting for current smoking as compared to never smoking
      when this cohort was in grades 8 and 11. METHODS: Current smoking was defined as
      reported regular or occasional smoking. Logistic regression and multiple
      regression models were tested separately for each gender and grade with variables
      entered in prespecified steps. RESULTS: Current smoking is more strongly related
      to psychosocial variables and environmental variables among older male
      adolescents as compared to younger ones. In older female adolescents, current
      smoking appears to be more strongly related to attitude variables and less
      strongly related to psychosocial variables than among younger female adolescents.
      There is some evidence that grade 11 males may use cigarettes as a coping
      strategy for depression. CONCLUSIONS: Male and female students differ in how
      stress and a range of psychosocial factors are interrelated with regards to
      current smoking and these relationships appear to change over time.

PMID- 15475038
TI  - Invariance study of an adolescent survey-based smoking-related cognitions scale:
      examination across Hispanic and Caucasian groups.
AB  - BACKGROUND: Large-scale surveys frequently assess tobacco-related cognitions,
      however, few studies have examined the psychometric properties and cultural
      invariance of such measures. METHODS: The present study examined the factor
      structure of a dichotomous 8-item tobacco-related beliefs scale administered as
      part of the state-wide California Tobacco Survey. It was expected that scale
      factor structure would be invariant across the non-Hispanic white (N = 1960) and
      English-speaking Mexican-Americans (N = 593), but would differ for Spanish
      speaking Mexican-Americans (N = 455). Invariance was also examined across gender
      within each group. RESULTS: A single factor solution was identified and confirmed
      within each group. Factorial invariance analyses revealed differences across the
      three groups as well as across gender among the Mexican-American groups.
      CONCLUSIONS: Findings underscore the importance of examining the psychometric
      properties of scales employed to assess tobacco-related cognitions across
      cultural and gender groups.

PMID- 15475039
TI  - A re-examination of the potential impact of preventive therapy on the public
      health problem of tuberculosis in contemporary sub-Saharan Africa.
AB  - BACKGROUND: To estimate the effect size of tuberculosis preventive therapy (PT)
      on the public health problem of tuberculosis in contemporary sub-Saharan Africa.
      METHODS: A compartmental flow model that considers high levels of tuberculosis
      and human immunodeficiency virus (HIV) infection in contemporary sub-Saharan
      Africa was used to assess the impact of PT on the prevalence of tuberculosis and
      tuberculosis-associated mortality. RESULTS: Model implementation shows that
      giving PT to 25% of HIV-positive individuals with latent tuberculosis infection
      (LTBI) leads to a 3.9% reduction in the prevalence of tuberculosis in 10 years
      and a 5.1% reduction in 20 years. This intervention also prevents a cumulative
      total of 3.0% of tuberculosis-associated deaths in a decade and 5.5% in two
      decades. Doubling PT coverage to 50% approximately doubles the effect size,
      suggesting a linear relationship within the 20-year period. The effect size is
      slightly sensitive to changes in level of HIV transmission, level of tuberculosis
      transmission, and level of case detection and treatment cure rates in the
      population. CONCLUSIONS: Contrary to suggestions by previous authors that PT can
      significantly reduce the public health problem of tuberculosis in sub-Saharan
      Africa, this model-based analysis suggests that the impact of PT on tuberculosis
      in the population is likely to be small.

PMID- 15475040
TI  - YOUTH: decisions and challenges in designing an osteoporosis prevention
      intervention for teen girls.
AB  - BACKGROUND: This paper describes decisions about the experimental design for the
      Youth, Osteoporosis, and Understanding Total Health Project (YOUTH), a trial
      designed to test the efficacy of a health plan-based lifestyle intervention for
      increasing bone mineral density among adolescent women 14 to 16 years of age.
      METHODS: This randomized controlled trial recruited adolescent women who were at
      higher risk for developing osteoporosis (body mass index 16-23) from a large HMO
      in the Pacific Northwest. The intervention focused on improving diet (high
      calcium foods, fruits, and vegetables) and increasing physical activity (high
      impact and spinal motion). The intervention included both group and individual
      activities. The primary endpoint in the study was total bone mineral density as
      measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: Baseline data were
      collected on the trial cohort of 228 adolescent women and their families. This
      paper discusses how researchers met the following challenges in designing and
      implementing the trial: determining appropriate dietary and exercise targets to
      affect bone mineral density in adolescents; choosing suitable assessments; and
      developing an intervention well suited for implementation in a non-school (health
      plan) setting. We also discuss the rationale for the specific study population
      chosen (females, younger adolescents). CONCLUSIONS: The YOUTH project is one of
      very few preventive research interventions with adolescents conducted in a health
      plan setting. Many of the recruitment and intervention strategies used in this
      trial may be appropriate for adoption in other health plan-based prevention
      studies.

PMID- 15475041
TI  - Barriers and motivations to exercise in older adults.
AB  - Although exercise is an established component in the management of many chronic
      diseases associated with aging, activity levels tend to progressively decline
      with increasing age. Given the growing proportion of older adults, these
      suboptimal levels of physical activity represent an increasing public health
      problem. The predicators of adherence elucidated in younger adults are unreliable
      in elderly populations. Age-specific barriers and motivators unique to this
      cohort are relevant and must be acknowledged. The identification of reliable
      predictors of exercise adherence will allow healthcare providers to effectively
      intervene and change patterns of physical activity in sedentary elderly. In
      particular, because older patients respect their physician's advice and have
      regular contact with their family doctor, physicians can play a key and pivotal
      role in the initiation and maintenance of exercise behavior among the older
      population.

PMID- 15475042
TI  - Families, peers, and contexts as multiple determinants of adolescent problem
      behavior.

PMID- 15475043
TI  - The role of family and peer relations in adolescent antisocial behaviour:
      comparison of four ethnic groups.
AB  - The dominant theories about the development of antisocial behaviour during
      adolescence are based almost entirely on research conducted with mainstream,
      white, middle-class adolescents. The present study addresses this significant gap
      in the literature by examining whether the same model of family and peer
      influence on antisocial behaviour is applicable to adolescents belonging to
      different ethnic groups. The sample included 603 adolescents (318 females and 285
      males) from four ethnic groups: 68% of adolescents were Dutch, 11% were Moroccan,
      13% were Turkish and 8% were Surinamese. The questionnaires assessing antisocial
      behaviour, quality of parent-adolescent relationship and involvement with deviant
      peers were completed by adolescents individually at schools. Results show few
      ethnic differences in the mean level of the assessed constructs: adolescents from
      different ethnic groups show similar levels of antisocial behaviour, are to a
      similar degree satisfied with their relationships with parents, disclose as much
      information to them, and do not differ in their involvement with deviant peers.
      However, the associations of parent and peer relations with antisocial behaviour
      differed across the ethnic groups.

PMID- 15475044
TI  - Premature adolescent autonomy: parent disengagement and deviant peer process in
      the amplification of problem behaviour.
AB  - Premature autonomy describes a developmental dynamic where parents of high-risk
      adolescents reduce their involvement and guidance when confronted with challenges
      of problem behaviour and the influence of deviant friendships. This dynamic was
      tested on the sample of Oregon Youth Study boys (N=206), whose family management
      practices and friendships were observed on videotaped interaction tasks. Latent
      growth curve models were used to examine longitudinal trends between deviant
      friendship interactions and family management. Direct observations of deviant
      friendship process at age 14 were associated with degradation in family
      management during adolescence. A comparison of antisocial and well-adjusted boys
      clarified that parents of antisocial boys (started early and persisted) decreased
      family management around puberty, in comparison to parents of well-adjusted boys
      who maintained high levels of family management through adolescence. In
      predicting late adolescent problem behaviour, there was a statistically reliable
      interaction between family management degradation and deviant peer involvement in
      adolescence in support of the premature autonomy hypothesis. Adolescent males
      involved in deviant friendships, and whose parents decreased their family
      management, were most likely to use marijuana and commit antisocial acts at age
      18. The implications for interventions that target adolescents are discussed.

PMID- 15475045
TI  - Influence and selection processes in friendships and adolescent smoking
      behaviour: the role of parental smoking.
AB  - Concerning the role of parental smoking on development of adolescent smoking,
      most studies have exclusively focused on the direct effects of parents' smoking
      on youths' smoking. However, parental smoking may also play an indirect role by
      affecting youths' susceptibility to peer influences and by affecting friendship
      selection. Data were from a three-wave short-term longitudinal study of 1595
      adolescents. Findings showed high similarities in smoking between reciprocal
      friends. Additionally, friend's smoking and parents' smoking were moderately
      related to adolescent smoking onset, but parents' smoking did not moderate the
      prospective association between best friend's smoking and adolescent smoking.
      Finally, parental smoking seemed to affect the selection of new friends: In
      particular, adolescents with smoking parents were most likely to become
      affiliated with smoking friends. There was no evidence that parental smoking
      affected termination of friendships.

PMID- 15475046
TI  - "Very Important Persons" in adolescence: going beyond in-school, single
      friendships in the study of peer homophily.
AB  - Using a sample of 1227 Swedish adolescents we examined peer relations across
      contexts and for multiple peer targets (three "Very Important Persons", VIPs).
      Specifically, we examined the relations between antisocial behaviour and the
      types of relationships individuals had with their VIPs (e.g. friend, romantic
      partner), the contexts in which they had met, and where they spent time (e.g.
      school, neighbourhood, club). Additionally, we tested an "additive homophily"
      hypothesis, or the idea that youths would show unique similarities to multiple
      peers. Results showed that individuals who nominated romantic partners as their
      first VIPs were the most antisocial (both boys and girls), and individuals who
      had met and spent time with their first VIPs in the neighbourhood were also the
      most antisocial. Similar results were found for the antisocial behaviour of the
      first VIP. Finally, results supported the additive homophily hypothesis, showing
      that significantly more variance in individual behaviour is explained when
      including second and third VIPs.

PMID- 15475047
TI  - Adolescent voting for right-wing extremist parties and readiness to use violence
      in political action: parent and peer contexts.
AB  - Almost all shapes of adolescent risky and deviant behaviour take place in the
      context of peer-relations. The present study examined the role of parents and
      peer-relations with respect to two indicators of deviant political development.
      In the fall 1998, directly after the German parliamentary elections, 1309 East
      German adolescents were asked about their voting for a right-wing extremist party
      and their readiness to use violence in political action. Friend's voting was a
      strong predictor of individual voting for a right-wing extremist party,
      particularly when the friend was the best friend with a reciprocal nomination,
      and when the friends frequently communicated about political themes. In addition,
      voting behaviour and willingness to use violence were associated with membership
      in peer groups who met frequently. Finally, the violence-disposed adolescents
      spent more of their spare time with peers and less with their parents.
      Similarities of our results with the findings of research on deviant behaviour in
      non-political areas support the idea that deviant political behaviour could be an
      expression of a problematic life situation.

PMID- 15475048
TI  - Why a leisure context is linked to normbreaking for some girls and not others:
      personality characteristics and parent-child relations as explanations.
AB  - In a study of adolescents in the 1970s, girls were high in normbreaking if they
      attended youth recreation centers and were heavily involved with peers or boys
      (Stattin et al., 2003). The present study investigated whether these results
      could be replicated on a modern sample, and then examined parent-child
      relationships and personality characteristics as explanations why some girls and
      not others go to the youth centers and become heavily involved with peers and
      boys. Participants were 1279 14-year olds from a city in central Sweden. The
      results showed that personality characteristics and experiences at home partly
      explained youth center attendance, and personality characteristics partly
      explained involvement with boys, but neither explained why those who attended the
      centers and were involved with boys were highest on normbreaking. Thus,
      personality characteristics and experiences at home seem to be involved when
      girls choose the youth center context, but socialization by peers at the centers
      might better explain normbreaking among center goers.

PMID- 15475049
TI  - Thermal and chemical stability of fluorohydroxyapatite ceramics with different
      fluorine contents.
AB  - Hydroxyapatite (HA) plays an important role in orthopedics and dentistry due to
      its excellent bioactivity. However, the thermal decomposition and the poor
      corrosion resistance in an acid environment have restricted the applications of
      HA. In this study, several fluorine-substituted hydroxyapatite (FHA) ceramics
      with the general chemical formula Ca10(PO4)6(OH)(2-2x)F2x, where x = 0.0, 0.2,
      0.4, 0.6, 0.8, 1.0, were prepared. Thermogravimetric analysis in the temperature
      range from 25 degrees C to 1400 degrees C showed that the FHA ceramics with x >
      0.4 had remarkably improved thermal stability as compared to pure HA. X-ray
      diffraction of the FHA ceramics sintered at 1300 degrees C for 1 h further
      confirmed the thermal stability. Dilatometer analysis showed that the fluorine
      addition substantially increased the onset sintering temperature of the FHA
      ceramics. Density measurements showed that the fluorine addition into the HA
      matrices slightly retarded the densification of the FHA ceramics. Corrosion
      testing on the polished surfaces of the FHA ceramics using a 2.5 wt% citric acid
      solution indicated that the FHA ceramics with x > or = 0.4 had substantially
      improved corrosion resistance.

PMID- 15475050
TI  - Variable cytocompatibility of six cell lines with photoinitiators used for
      polymerizing hydrogels and cell encapsulation.
AB  - The development of biocompatible photopolymerizing polymers for biomedical and
      tissue engineering applications has the potential to reduce the invasiveness and
      cost of biomaterial implants designed to repair or augment tissues. However, more
      information is needed about the cellular toxicity of the compounds and initiators
      used in these systems. The current study evaluates the cellular toxicity of three
      ultraviolet sensitive photoinitiators on six different cell populations that are
      used for engineering numerous tissues. The photoinitiator 2-hydroxy-1-[4
      (hydroxyethoxy)phenyl]-2-methyl-1-propanone (Irgacure 2959) caused minimal
      toxicity (cell death) over a broad range of mammalian cell types and species. It
      was also demonstrated that different cell types have variable responses to
      identical concentrations of the same photoinitiator. While inherent differences
      in the cell lines may contribute to the variable cytotoxicity, a correlation
      between cellular proliferation rate (population doubling time) and increased
      cytotoxicity of the photoinitiator was observed. Cell lines that divided more
      quickly were more sensitive to photoinitiator-induced cell death. In summary, the
      photoinitiator Irgacure 2959 is well tolerated by many cell types over a range of
      mammalian species. Cell photoencapsulation strategies may be optimized to improve
      cell survival by manipulating proliferation rate.

PMID- 15475051
TI  - Surface properties and cell response of low metal ion release Ti-6Al-7Nb alloy
      after multi-step chemical and thermal treatments.
AB  - Ti-6Al-7Nb samples treated by innovative multi-step chemical and thermal
      processes were characterized in order to evaluate their surface properties and
      cell interaction. The main object was to asses if the treatments were effective
      in order to obtain a surface presenting at the same time bone-like apatite
      induction ability, low metal ion release, good cell response and high protein
      binding. The morphology, crystallographic structure, porosity and wettability of
      the treated materials were investigated, as well as their interaction with
      simulated body fluid during soaking for different times. Cytotoxicity, protein
      adsorption tests and in vitro fibroblast and osteoblast-like cell cultures were
      also performed.

PMID- 15475052
TI  - Coil dimensions of the mussel adhesive protein Mefp-1.
AB  - To obtain a better understanding of factors controlling cross-linking rates of
      Mussel adhesive proteins, we study the conformation of the Mussel Adhesive
      Protein Mefp-1. The dimensions of Mefp-1 in solution are determined by dynamic
      light scattering. Under physiological conditions, the hydrodynamic radius RH of
      Mefp-1 is found to be 10.5+/-1.1 nm. Measured Mefp-1 dimensions are compared with
      theoretical dimensions of Mefp-1 in random coil conformations. We have strong
      indications that Mefp-1, under dilute and physiological conditions, has a self
      avoiding random walk conformation with helix-like deca-peptide segments. With a
      number of segments of approximately 90, the segment length is found to be 2.7 nm.

PMID- 15475053
TI  - Tannic acid treatment enhances biostability and reduces calcification of
      glutaraldehyde fixed aortic wall.
AB  - Progressive degeneration and calcification of glutaraldehyde (Glut) fixed tissues
      used in cardiovascular surgery restrict their long-term clinical performance.
      This limited biological stability may be attributable to the inability of Glut to
      adequately protect certain tissue components such as elastin from enzymatic
      attack. The aim of our studies was to develop novel tissue-processing techniques
      targeted specifically at elastin stabilization by using tannic acid (TA), a plant
      polyphenol capable of protecting elastin from digestion by specific enzymes. In
      present studies we demonstrated that Glut does not adequately protect porcine
      aorta from elastase-mediated degradation in vitro. The addition of TA to the Glut
      fixation process increased the stability of Glut-fixed aorta to elastase
      digestion by 15-fold and also decreased calcification in the rat subdermal model
      by 66%. TA was found to be chemically compatible with Glut fixation and did not
      hinder collagen crosslinking as shown by minor changes in thermal denaturation
      temperatures, resistance to collagenase and mechanical properties. In vitro and
      in vivo studies also revealed that TA binding to aortic wall was stable over an
      extended period of time. TA-mediated elastin stabilization in Glut-fixed
      cardiovascular implants may significantly extend the clinical durability of these
      tissue replacements.

PMID- 15475054
TI  - Encapsulation of chondrocytes in injectable alkali-treated collagen gels prepared
      using poly(ethylene glycol)-based 4-armed star polymer.
AB  - An in situ gel system was developed to encapsulate chondrocytes under
      physiological conditions using an alkali-treated collagen (AlCol) and
      pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-PEG)
      as a crosslinker. AlCol gels were obtained at crosslinker concentrations from 0.1
      to 3.0 mM. Chondrocytes were encapsulated and dispersed homogeneously in AlCol
      gels. Results of MTT staining showed that cells survived after encapsulation in
      AlCol gels. Biochemical analysis demonstrated that DNA content in AlCol gels was
      constant after 3 weeks. Glycosaminoglycan content and mRNA expression of type II
      collagen and aggrecan increased with culture time. These results suggest that
      this in situ gel system is useful for regenerating cartilage in vitro and for
      minimally invasive therapy for cartilage defects.

PMID- 15475055
TI  - Cartilage tissue engineering PLLA scaffold with surface immobilized collagen and
      basic fibroblast growth factor.
AB  - A previously reported "grafting and coating" method (J. Biomed. Mater. Res.
      (Appl. Biomater.) 63 (2002) 838) was modified and used to introduce stable
      collagen layer and incorporate basic fibroblast growth factor (bFGF) on PLLA
      scaffold surface to prepare tissue engineering scaffold with improved
      biocompatibility. To make the modification of the 3-D porous PLLA scaffold
      possible, grafting of polymethacrylic acid (PMAA) onto the PLLA surface was
      initiated by the -OOH/Fe2+ system instead of the UV light used in the former
      method. Water soluble carbodimmide chemistry was applied to graft collagen onto
      the PLLA scaffold surface, followed by physical coating of the collagen solution
      with or without basic fibroblast growth factor (bFGF). Surface modification of 2
      D PLLA membrane was also done for fundamental understanding of the modification.
      The -COOH density on/in the PMAA grafted PLLA membrane/scaffold was measured by
      colorimetric method and the collagen content on/in the collagen immobilized PLLA
      membrane/scaffold was measured by ninhydrin method. Chondrocyte culturing on the
      collagen immobilized PLLA surfaces showed significantly improved cell spreading
      and growth. Incorporation of fibroblast growth factors in the collagen layer
      further enhanced the cell growth. This convenient and effective method can be
      used to prepare bioactive scaffolds with extra cellular matrix (ECM)-mimic
      composition for tissue engineering.

PMID- 15475056
TI  - Nanofiber alignment and direction of mechanical strain affect the ECM production
      of human ACL fibroblast.
AB  - The effects of fiber alignment and direction of mechanical stimuli on the ECM
      generation of human ligament fibroblast (HLF) were assessed. The nanofiber matrix
      was fabricated using electrospinning technique. To align the nanofibers, a
      rotating target was used. The HLFs on the aligned nanofibers were spindle-shaped
      and oriented in the direction of the nanofibers. The degree of ECM production was
      evaluated by comparing the amount of collagen on aligned and randomly oriented
      structures. Significantly more collagen was synthesized on aligned nanofiber
      sheets, although the proliferation did not differ significantly. This suggests
      that the spindle-shape observable in intact ligaments is preferable in producing
      ECM. To evaluate the effect of strain direction on the ECM production, HLFs were
      seeded on parallel aligned, vertically aligned to the strain direction, and
      randomly oriented nanofiber sheets attached to Flexcell plates. After a 48-h
      culture, 5% uniaxial strain was applied for 24h at a frequency of 12 cycles/min.
      The amounts of collagen produced were measured 2 days after halting the strain
      application. The HLFs were more sensitive to strain in the longitudinal
      direction. In conclusion, the aligned nanofiber scaffold used in this study
      constitutes a promising base material for tissue-engineered ligament in that it
      provides more preferable biomimetic structure, along with proper mechanical
      environment.

PMID- 15475057
TI  - The role of macrophages in osteolysis of total joint replacement.
AB  - The osteolysis associated with conventional polyethylene on metal total joint
      replacements is associated with the formation of an inflamed periprosthetic
      membrane rich in macrophages, cytokines and implant-derived wear particles. There
      is a wealth of evidence to indicate that the presence and activation of
      macrophages in the periprosthetic tissues around joint replacements is stimulated
      by UHMWPE particles. Particles within the size range 0.1-1.0 microm have been
      shown to be the most reactive. Animal studies have provided increasing evidence
      that, of the milieu of cytokines produced by particle-stimulated macrophages, TNF
      alpha is a key cytokine involved in osteolysis. Recent advances in the
      understanding of the mechanisms of osteoclastogenesis and osteoclast activation
      at the cellular and molecular level have indicated that bone marrow-derived
      macrophages may play a dual role in osteolysis associated with total joint
      replacement. Firstly, as the major cell in host defence responding to UHMWPE
      particles via the production of cytokines and secondly as precursors for the
      osteoclasts responsible for the ensuing bone resorption.

PMID- 15475058
TI  - Poly(N-isopropylacrylamide)-graft-polypropylene membranes containing adsorbed
      antibody for cell separation.
AB  - We developed a novel selective cell-separation method based on using a poly(N
      isopropylacrylamide)-graft-polypropylene (PNIPAAm-g-PP) membrane containing
      adsorbed monoclonal antibody specific to the target cell. This membrane was
      prepared by plasma-induced polymerization and soaking in an antibody solution at
      37 degrees C. Poly(N-isopropylacrylamide) has a thermoresponsive phase
      transition: at 32 degrees C water-insoluble (hydrophobic) and water-soluble
      (hydrophilic) states interconvert. Adsorption of antibody onto PNIPAAm-g-PP
      membrane at 37 degrees C and its desorption at 4 degrees C was verified by
      fluorescence-microscopy of the PNIPAAm-g-PP membrane after soaking it in
      fluorescein-conjugated goat anti-mouse IgG in phosphate-buffered saline. PNIPAAm
      g-PP membranes containing adsorbed anti-mouse CD80 monoclonal antibody
      preferentially captured mouse-CD80 transfected cells at 37 degrees C compared
      with membranes lacking antibody or containing anti-mouse CD86 monoclonal
      antibody. Detachment of captured cells from PNIPAAm-g-PP membranes was
      facilitated by washing at 4 degrees C because of the thermoresponsive phase
      transition of PNIPAAm. With this method, mouse CD80- or mouse CD86-transfected
      cells were enriched from a 1:1 cell suspension to 72% or 66%, simply and with
      high yield.

PMID- 15475059
TI  - Ocular release of timolol from molecularly imprinted soft contact lenses.
AB  - The aim of this study was to evaluate "in vivo" the usefulness of molecular
      imprinting technology to obtain therapeutic soft contact lenses capable of
      prolonging the permanence of timolol in the precorneal area, compared to
      conventional contact lenses and eyedrops. Soft contact lenses (diameter 14 mm,
      center thickness 0.08 mm) consisted of N,N-diethylacrylamide (DEAA; main
      component of the matrix), methacrylic acid (MAA; functional monomer) and ethylene
      glycol dimethacrylate (EGDMA; cross-linker) were prepared by the conventional
      methodology (non-imprinted) or by applying a molecular imprinting technique using
      timolol as the template (imprinted ones). After washing and reloading, timolol
      release studies carried out in rabbits showed that the soft contact lenses made
      by the molecular imprinting method (34 microg dose) provided measurable timolol
      concentrations in the tear fluid for 2.0- and 3.0-fold longer than the non
      imprinted contact lenses (21 microg dose) and eyedrops (doses of 34 and 125
      microg), respectively. Furthermore, the area under the timolol concentration-time
      curve (AUC) was 3.3- and 8.7-fold greater for imprinted contact lenses than non
      imprinted contact lenses and eyedrops, respectively. The timolol concentration of
      the eyedrops did not affect the precorneal residence time of drug significantly.
      On the other hand, timolol loading capacity of the contact lenses was improved by
      the molecular imprinting method; the sustaining of the drug levels in the tear
      fluid being proportional to the loading capacity of the contact lenses. These
      results indicate that imprinted soft contact lenses are promising drug devices
      able to provide greater and more sustained drug concentrations in tear fluid with
      lower doses than conventional eyedrops.

PMID- 15475060
TI  - Development and characterization of biodegradable nanospheres as delivery systems
      of anti-ischemic adenosine derivatives.
AB  - We report a preliminary study concerning the encapsulation modalities in
      nanoparticles of the anti-ischemic drug N6-cyclopentyladenosine (CPA) and its pro
      drug 5'-octanoyl-CPA (Oct-CPA). The release of these compounds and the related
      pro-drug stability effects in human whole blood have been tested. Moreover, the
      influence of the delivery systems on CPA interaction toward human adenosine A1
      receptor has been analysed. The nanospheres were prepared by nanoprecipitation or
      double emulsion solvent evaporation method using poly(lactic acid) and recovered
      by gel filtration or ultracentrifugation or dialysis. Free and encapsulated Oct
      CPA was incubated in fresh blood and its stability was analysed with HPLC. Quite
      spherical nanoparticles with mean diameters ranging between 210+/-50 and 390+/-90
      nm were obtained. No encapsulation occurred when CPA was used. Satisfactory
      results concerning drug content (0.1-1.1% w/w) and encapsulation efficiency (6
      56%) were achieved when Oct-CPA was employed. The controlled release of the pro
      drug was achieved, being released within a range of 1-4 h, or very slowly,
      depending on nanoparticle preparations. The hydrolysis rate of Oct-CPA in human
      whole blood appeared stabilized in human whole blood with modalities related to
      the release patterns. The presence of all nanoparticle preparations did not
      interfere with CPA interaction at its action site.

PMID- 15475061
TI  - Preparation and physicochemical characterization of biodegradable nerve guides
      containing the nerve growth agent sabeluzole.
AB  - The objective of this study was to develop and characterize a biodegradable drug
      loaded nerve guide for peripheral nerve regeneration. Sabeluzole, a nerve growth
      agent, was selected as model compound. Four biodegradable polymers were selected
      for this study: a copolymer of polylactic acid and polycaprolactone (PCL); a
      copolymer of polyglycolic acid and polycaprolactone PCL; a copolymer of
      PCL/polydioxanone (PDO) and PDO. Placebo and drug loaded nerve guides were
      obtained by melt compression and melt extrusion. It was observed that melt
      compression and melt extrusion are feasible techniques to prepare the nerve
      guides. Based on the physicochemical characterization, all samples show absence
      of crystalline sabeluzole, indicating the formation of an amorphous dispersion.
      The in vitro release measurements show that the release of sabeluzole is
      complete, reproducible and can be controlled by the proper selection of the
      polymer. The release mechanism for all samples follows Fickian release behaviour.

PMID- 15475062
TI  - Rietveld refinements and spectroscopic studies of the structure of Ca-deficient
      apatite.
AB  - Nine samples of Ca-deficient apatite (Ca-def Ap) were prepared from suspensions
      of CaHPO4 (monetite) at 90 degrees C by raising the pH from approximately 4
      through release of NH3 produced by the hydrolysis of urea. Products were dried at
      100 degrees C for 24h and studied by chemical analyses, X-ray powder diffraction
      (XRPD) (and Rietveld analysis of this data), Ca/P ratio determination
      (quantitative phase analysis of samples after heating to 900 degrees C from
      Rietveld analysis of XRPD data), scanning electron microscopy, He pycknometry, 1H
      and 31P MAS NMR spectrometry and Fourier transform infrared and Raman
      spectroscopy. All samples contained apatite, but three also contained monetite.
      Infrared and Raman spectroscopy confirmed the presence of HPO4(2-) and absence of
      carbonate ions in the six monetite-free samples. Mean results for the six samples
      were: a = 9.4320(40), c = 6.8751(31) A; unit cell formula from chemical analysis
      neglecting protonation of phosphate ion,
      Ca(9.303(50))(PO4)6(OH)(0.606(99)).1.97(12)H2O; theoretical density 3.10 g cm(
      3); experimental density (mean for three samples) 3.15 g cm(-3); and Ca/P mole
      ratio from chemical analysis and phase analysis after heating to 900 degrees C,
      1.550(8) and 1.550(2), respectively. An earlier assignment of a line at 6 ppm in
      the 1H NMR spectrum of similar samples to HPO4(2-) ions could not be confirmed;
      hence no information about the HPO4(2-) ion content could be derived, in
      disagreement with the previous NMR study. A shoulder at approximately 0.9 ppm
      relative to 85 wt% H3PO4 in the 31P NMR spectrum was assigned to HPO4(2-) ions.
      Occupancies from the Rietveld structure refinements indicated preferential loss
      of Ca from Ca2 sites compared with Ca1, but the loss was substantially smaller
      than expected from chemical analyses. It is suggested that imperfect modelling of
      the structure in the refinement, particularly disorder associated with the Ca2
      site, resulted in errors in Ca2 occupancies. The P-O bonds were slightly shorter
      than those in stoichiometric hydroxyapatite, rather than longer as might be
      expected from protonation of phosphate tetrahedra. However, consideration of
      known acid phosphate structures indicated that it was unlikely that the increase
      in P-O lengths would be sufficient to be detected. The observed decrease was
      tentatively assigned to the presence of Ca2+ ion vacancies.

PMID- 15475063
TI  - Malignant hematopoietic cell lines: in vitro models for the study of
      erythroleukemia.
AB  - A panel of leukemia cell lines has been assembled over the last 30 years
      representing a spectrum of erythroid cells arrested at various stages of
      differentiation. The oldest cell line is K-562 which is one of the most prolific
      in use. Most cell lines have been established from acute myeloid leukemia M6 or
      chronic myeloid leukemia in blast crisis and generally express immunoprofiles
      typically seen in immature erythroid cells. Several cell lines are constitutively
      growth factor-dependent, responding proliferatively to a variety of cytokines.
      The predominant cytogenetic abnormalities are the t(9;22)(q34;q11) found
      exclusively in CML-derived cell lines, and rearrangements of chromosomes 5 and 7
      which occur in all disease subtypes. Ph+ve cell lines consistently displayed
      structural and numerical changes associated with disease evolution, including +8,
      -17/17p-/i(17q), and +19. It is striking that many cell lines though committed to
      either the erythroid or megakaryocytic lineage tend to co-express features of the
      other lineage, consistent with the concept of a common erythroid-megakaryocytic
      progenitor. Several cell lines may be induced to differentiate along the
      erythroid, megakaryocytic or monocytic pathway by treatment with pharmacological
      or physiological reagents. Notable functional features include expression of
      various globin chains or the complete hemoglobins as erythroid attributes. Taken
      together, this class of cell lines is relatively well characterized and affords
      useful model systems for immature erythroid cells.

PMID- 15475064
TI  - Taking the measure of alemtuzumab.

PMID- 15475065
TI  - Alemtuzumab: validation of a sensitive and simple enzyme-linked immunosorbent
      assay.
AB  - Alemtuzumab (MabCampath) is a humanized rat monoclonal antibody that targets the
      CD52 antigen. It has been approved for the treatment of patients with resistant
      chronic lymphocytic leukaemia (CLL). Measuring plasma/serum levels of alemtuzumab
      is important for optimizing the dosing and scheduling of therapy; however,
      current assays in serum or plasma, based on the capture of alemtuzumab using
      CD52, are complicated and difficult to adapt for high throughput testing. We
      developed a simple sandwich enzyme-linked immunosorbent assay (ELISA) to measure
      alemtuzumab that takes advantage of the remaining rat sequence in alemtuzumab.
      Using specific anti-rat immunoglobulin (Ig) antibodies (absorbed against human
      Ig), alemtuzumab levels were measured in the serum and plasma of patients treated
      with alemtuzumab. Levels were similar between plasma and serum samples, in fresh
      samples and samples stored at 4 degrees C for 24 h, but were significantly lower
      in samples stored at room temperature for 24h. The assay was successfully used to
      determine serum alemtuzumab pre- and post-treatment. This assay is simple and
      adaptable for high throughput testing, with a limit of detection of 0.05
      microg/ml and a coefficient of variation of +/-12.5%. No false positivity was
      observed in >200 samples tested. This validated assay should help optimize the
      dosing and scheduling of alemtuzumab therapy. The underlying principles are also
      applicable to the measurement of other humanized antibodies using an appropriate
      anti-Ig.

PMID- 15475066
TI  - Alcohol intake and incidence of de novo adult acute leukemia.
AB  - In a case-control study of adult acute leukemia we defined alcohol intake as
      either non-regular (<1 drink per week), light (1-5 drinks per week), moderate (6
      8 drinks per week) or heavy (>8 drinks per week). An inverse association was
      found for light and moderate beer intake (RR = 0.58; 95% CI: 0.44, 0.76). In
      contrast, a positive association was found for moderate and heavy wine intake (RR
      = 2.1; 95% CI: 1.2, 3.8). Divergent results might reflect the effect of different
      nutrients in beer and wine, unmeasured confounding, or differing impacts of
      selection bias on these associations.

PMID- 15475067
TI  - Nonclonal neutrophil responses after successful treatment of myelodysplasia with
      low-dose 5-aza-2'-deoxycytidine (decitabine).
AB  - The demethylating agents 5-aza-2'-deoxycytidine (decitabine, DAC) and 5
      azacytidine at low doses induce hematologic and cytogenetic remissions in a
      subset of patients with MDS. It is unclear whether the correction of neutropenia
      involves differentiation of abnormal granulocyte precursors, or emergence of
      normal granulopoiesis. A previous study in three MDS patients, analyzing a
      differentiating activity of GM-CSF, had shown heterogenous granulocyte responses.
      The objective of our study was to determine the ratio of clonal and nonclonal
      peripheral blood granulocytes in MDS patients treated with DAC using FISH
      analysis. In two patients with initial severe neutropenia, an informative
      cytogenetic marker, complete normalization of peripheral blood neutrophils and a
      bone marrow cytogenetic response following DAC, >90% of the cells contributing to
      neutrophil normalization lacked this clonal marker. In one of them, an early and
      transient increase in clonal neutrophils was compatible also with a modest
      differentiating effect upon the dysplastic granulocyte precursors, whereas in a
      third patient, resistant to re-treatment with DAC, no expansion of either
      granulocyte population occurred. In the responders, leukocyte nadirs following
      DAC appeared less pronounced after conversion to normal cytogenetics. In
      conclusion, restoration of nonclonal hematopoiesis may be the predominant effect
      of DAC both in early and late stages of treatment, at least in patients achieving
      a hematologic and cytogenetic response.

PMID- 15475068
TI  - Histopathologic verification of acute leukemia (AL) in a cohort of 463 post
      Chernobyl patients from Belarus, Russia and Ukraine.
AB  - Seven morphologists examined 382 slide and 82 non-slide, post-Chernobyl pediatric
      acute leukemia (AL) cases in radiation-exposed areas of Belarus, Russia and
      Ukraine; part of a case-control study by the International Consortium for
      Research on the Health Effects of Radiation. Among the slide cases, 99% were
      confirmed as AL: 92% acute lymphoid leukemia (ALL) and 86% acute myeloid leukemia
      (AMD demonstrating the utility of FAB classification for distinguishing ALL and
      AML. Among the non-slide cases, 79% were confirmed as AL: 84% ALL, and 71% AML.
      This study affirms AL diagnostic accuracy during a time of social upheaval in the
      former Soviet Union.

PMID- 15475069
TI  - Association of CYP3A4 genotype with detection of Vgamma/Jbeta trans
      rearrangements in the peripheral blood leukocytes of pediatric cancer patients
      undergoing chemotherapy for ALL.
AB  - Cancer patients receiving chemotherapy are exposed to high doses of cytotoxic and
      genotoxic drugs which, in some cases, can lead to treatment related leukemia.
      Since this only occurs in a minority of patients, however, it is possible some
      individuals are predisposed due to genetic polymorphisms in genes for enzymes
      that mediate drug metabolism. To address this possibility we measured the
      genotoxicity of chemotherapeutic agents in patients receiving treatment for ALL
      by the frequency of the Vgamma/Jbeta trans-rearrangement in their peripheral
      blood leukocytes and compared this with CYP3A4 genotype. CYP3A4 is the most
      abundant of the cytochrome P450 (CYP) enzyme in the liver and intestine which
      contains a common -392A>G substitution in the promoter region (CYP3A4*1B allele).
      We found a significant increase in the frequency of rearrangements during
      chemotherapy only in patients homozygous for the wild type CYP3A4*1A allele. This
      provides a direct link between CYP3A4 genotype and susceptibility to drug
      genotoxicity thus strengthening the possibility that predisposition to treatment
      related leukemia may be measurable by simple genetic testing.

PMID- 15475070
TI  - Clinicopathological features and prognostic factors of Japanese patients with
      "peripheral T-cell lymphoma, unspecified" diagnosed according to the WHO
      classification.
AB  - Clinicopathological features of 36 patients, male: 58.3%; median: 68 years, with
      "peripheral T-cell lymphoma, unspecified" diagnosed by the WHO criteria were
      reviewed. Majority (69.4%) had stage IV disease with frequent involvements into
      bone marrow, spleen, liver, and skin. According to the IPI, 72.2% were
      categorized as high or high-intermediate risk group. CR and PR were achieved in
      12 and 10 out of 31 patients treated by CHOP-based chemotherapy, respectively.
      One- and two-year overall survivals were 60.6 and 25.0%, respectively.
      Performance status, serum LDH, and B symptom were significant prognostic factors.
      Survival of CD4-/CD8+ cases, corresponding to cytotoxic T-cell lymphoma, was
      significantly worse than that of CD4+/CD8-.

PMID- 15475071
TI  - Methylation status of cyclin-dependent kinase inhibitor genes within the
      transforming growth factor beta pathway in human T-cell lymphoblastic
      lymphoma/leukemia.
AB  - Epigenetic silencing of downstream components of the transforming growth factor
      beta pathway including the cyclin-dependent kinase inhibitors (CDKIs) p15INK4B,
      p27KIP1 and p21CIP1 is implicated in the pathogenesis of some hematological
      malignancies. Loss of p15INK4B expression due to promoter methylation occurs
      frequently in human T-cell acute lymphoblastic leukemia (T-ALL) but the
      expression and methylation status of p27KIP1 remains to be characterized in T-ALL
      or T-cell lymphoblastic lymphoma (T-LBL). As well, while some have reported a
      high frequency of p21CIP1 methylation in ALL patient samples others have found
      the gene to be unmethylated in this disease and the relationship between p21CIP1
      expression and promoter methylation has not been examined in T-LBL. Using RNase
      protection assays (RPA) and methylation specific PCR (MSP), we found p27KIP1 to
      be expressed and its promoter unmethylated in 20 of 20 (100%) and 28 of 28 (100%)
      T-LBL/ALL samples, respectively. In contrast, p21CIP1 mRNA was absent in 7 of 14
      (50%) T-LBL biopsies and 5 of 6 (83%) T-ALL cell lines. However, like p27KIP1
      there was no evidence of p21CIP1 promoter methylation by MSP or temporal
      temperature gradient electrophoresis (TTGE) analysis of 35 CpG sites in any of
      the 28 T-LBL/ALLs analyzed. Similar to T-ALL, we found p15INK4B mRNA was absent
      in 13 of 14 (93%) T-LBL biopsies and its promoter methylated in 6 of 10 (64%)
      cases. Our results indicate that p21CIP1 mRNA is absent in human T-LBL biopsies
      and T-ALL cell lines at a high frequency. However, unlike p15INK4B, reduced
      p21CIP1 expression in T-LBL/ALL is independent of dense promoter-associated CpG
      methylation. In contrast to some hematological malignancies p27KIP1 methylation
      does not appear to contribute significantly to T-LBL/ALL pathogenesis.

PMID- 15475072
TI  - Induction of anti-leukemic cytotoxic T lymphocytes by fusion of patient-derived
      dendritic cells with autologous myeloblasts.
AB  - Presentation of AML antigens by dendritic cells (DC) could potentially induce a T
      cell-mediated anti-leukemic immune response. In the present study, we generated
      DC from adherent (AD-DC) and non-adherent (NAD-DC) myeloblasts obtained from bone
      marrows of AML patients. Both cell populations displayed morphological,
      phenotypic and functional properties of DC. The functions of NAD-DC were compared
      to AD-DC that had been fused with autologous AML blasts (FC/AML). The FC/AML
      induced greater T cell proliferation and CTL activity against autologous AML
      blasts (9/10 cases) as compared to NAD-DC. FC/AML may thus represent a promising
      strategy for DC-based immunotherapy of patients with AML.

PMID- 15475073
TI  - Expression of P2X7 in human hematopoietic cell lines and leukemia patients.
AB  - The P2X7 nucleotide receptor is an adenosine 5'-triphosphate (ATP) -gated ion
      channel, which is widely expressed in cells of hematopoietic origin and functions
      as a non-selective cation channel permeable to Na+, Ca2+, etc upon stimulation.
      Here, we investigated P2X7 expression in 11 human hematopoietic cell lines,
      representing different lineages, as well as bone marrow mononuclear cells (BMMC)
      samples from 87 leukemia and 10 myelodysplastic syndrome (MDS) patients. Semi
      quantitative reverse transcription polymerase chain reaction (RT-PCR) and flow
      cytometry results showed that both P2X7 mRNA and protein were detected in eight
      cell lines with a non-lineage-specific manner. Samples from 69 leukemia and 9 MDS
      patients were P2X7 positive at mRNA level. Moreover, both positive rates and
      relative expression levels were significantly higher in acute myelogenous
      leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia
      (CML), and MDS groups than that in normal donor group. The expression levels
      varied among AML subtypes with higher levels being observed in M4, M5, and M6
      groups but not in M1 or M2 group. Furthermore, after one course of standard
      induction therapies, the remission rate in high P2X7 expression group was lower
      than that in either P2X7 negative group or low P2X7 expression group. Cytoplasmic
      free calcium increase was detected in five of eight P2X7+ cell lines as well as
      P2X7+ normal donor and patient samples tested, but not in three Epstein-Barr
      virus (EBV) positive cell lines (J6-1, Namalwa, and LCL-H) in Locke's solution
      upon stimulation by extracellular ATP or the more potent and specific agonist,
      2',3'-O-(4-benzoyl)benzoyl-ATP (BzATP). The possible mechanisms causing the loss
      of P2X7 function were discussed.

PMID- 15475074
TI  - Effects of hyperthermia on the differentiation and growth of K562 erythroleukemic
      cell line.
AB  - Several agents are known to induce differentiation in the human erythroleukemic
      cell line K562. In this work we have studied the ability of hyperthermia to
      induce differentiation in the K562 cell line. K562 cells were treated with
      hyperthermia in the range of 41-45 degrees C. Cell proliferation and the plating
      efficiency of heat treated cells along with their hemoglobin synthesis was
      measured and compared with controls. Hyperthermia severely inhibited the growth
      of K562 cells in the suspension culture in a time- and temperature-dependent
      manner. Sixty minutes of heating and 44 and 40 min of heating at 45 degrees C
      totally inhibited the growth of the cells. The number of clonogenic cells also
      decreased as a result of heat treatment. Extended periods of heating for more
      than 2 h at 41 degrees C resulted in thermal adaptation. Hyperthermia-induced
      hemoglobin synthesis by these cells, only at 42 and 43 degrees C. Maximum
      induction was observed after heat treatment for 80 min at 43 degrees C and 180
      min at 42 degrees C. At lower temperature, although the fraction of surviving
      cells was high, but no signs of hemoglobin synthesis could be observed. At
      temperatures higher than 43 degrees C, the fraction of surviving cells decreased
      rapidly and also no signs of hemoglobin synthesis could be detected. At the two
      selective temperatures, hemoglobin synthesis started 4 days after heat treatment.
      The results showed that hyperthermia caused cytotoxicity and growth arrest and
      induced differentiation as judged by hemoglobin synthesis and reduced
      clonogenicity in this cell line. This is the first time that a physical agent has
      been shown to induce differentiation in erythroleukemic cell lines.

PMID- 15475076
TI  - The p73 locus is commonly deleted in non-Hodgkin's lymphomas.
AB  - Rearrangements involving the 1p36 chromosomal region occur frequently in NHL,
      suggesting the existence of tumor suppressor gene(s) that are important in
      lymphomagenesis. p73 is closely related to the tumor suppressor p53 and maps to
      the chromosome 1p36 region. Here we report heterozygous deletions of the p73
      locus in 25% of FL and 27% of DLBCL cases, as detected by FISH.
      Immunohistochemical analysis showed that four out of five cases with p73
      deletions also exhibited increased Ki67 expression, indicating higher
      proliferation rates of the tumor cells. Our results demonstrate a high proportion
      of p73 locus specific deletions in NHL and suggest that deletion of this locus
      may play a role in the progression of NHL.

PMID- 15475075
TI  - Establishment and characterization of a new human erythroleukemic cell line, ERY
      1.
AB  - The growth factor-independent erythroleukemic cell line ERY-1 was established
      from the peripheral blood of a 87-year-old woman with chronic myeloid leukemia
      (CML) in the acute phase. Immunophenotyping showed that fresh leukemic cells were
      positive for CD13, CD33, CD36 and CD235a (glycophorin A), a phenotype compatible
      with that of erythroblastic cells. Cytogenetic and fluorescence in situ
      hybridization (FISH) analysis demonstrated classical t(9;22)(q34;q11) chromosomic
      translocation associated with a duplication of the BCR-ABL fusion gene. Other
      cytogenetic abnormalities were detected in all analyzed mitosis, the most
      frequent being a trisomy of chromosome 8. The established ERY-1 cell line retains
      these immunophenotypic and cytogenetic features, and light and electron
      microscopy confirmed the relatively mature erythroblastic phenotype of the cells.
      In addition, ERY-1 cell line expressed beta-globin mRNA and a non-phosphorylable
      form of the erythropoietin receptor, even in presence of erythropoietin. Of note,
      the proliferation of ERY-1 cells was inhibited by TGFbeta1 or STI-571 (Gleevec),
      without significant induction of further differentiation. In conclusion, ERY-1 is
      a new growth factor-independent human erythroleukemic cell line with a relatively
      mature phenotype that may be useful to study the molecular events involved in
      erythroblastic differentiation.

PMID- 15475077
TI  - Treatment of acute promyelocytic leukemia in the very elderly: case report and
      review of the literature.
AB  - Acute promyelocytic leukemia (APL) is the most curable subtype of AML yet it is
      not known to what extent newer therapies will succeed in the very elderly.
      Conventional chemotherapeutic induction regimens are usually too toxic for older
      patients, however, all trans-retinoic acid (ATRA) and arsenic trioxide (ATO) may
      be useful therapeutic options if used judiciously. This case series describes
      three octogenarians with APL all treated with ATRA and achieved complete
      remissions. The last patient received ATO at the time of first relapse and
      achieved a second remission. To our knowledge, this is the first report of
      successful use of ATO for induction in an octogenarian with APL.

PMID- 15475078
TI  - Hematologic malignancies, critical genes and representative pictures for 166
      chromosome anomalies.

PMID- 15475079
TI  - Complex cytogenetics in a case of probably work related MDS/AML.
AB  - In the majority of cases of overt acute myeloid leukemia (AML), there is no
      knowledge about a preleukemic phase of myelodysplastic syndrome (MDS). A few
      recent case-control studies suggest an association between MDS and several
      occupations. We report a unique case of MDS/AML related to the patient's work
      condition with numerous cytostatic agents. The karyotype revealed a spectrum of
      genetic rearrangements identified by conventional cytogenetics, fluorescence in
      situ hybridization (FISH) and spectral karyotyping (SKY). We suggest that
      amplification of chromosomal material may play a greater role in leukemogenesis
      than has been recognized previously.

PMID- 15475080
TI  - Is the American Board of Surgery certifying examination archaic?

PMID- 15475081
TI  - Management of the difficult duodenum.

PMID- 15475082
TI  - Regulatory cells.

PMID- 15475083
TI  - Wrong-site surgery: avoiding the obvious.

PMID- 15475084
TI  - Cancer of the larynx: new approaches for organ preservation.

PMID- 15475085
TI  - Evaluating mild to moderate brain injuries.

PMID- 15475086
TI  - What price should be paid for organs?

PMID- 15475088
TI  - Biliary dyskinesia: a brief review.

PMID- 15475089
TI  - Abdominal distention and diarrhea in a young female.

PMID- 15475090
TI  - John Benjamin Murphy.

PMID- 15475093
TI  - A 360 degrees evaluation of a night-float system for general surgery: a response
      to mandated work-hours reduction.
AB  - PURPOSE: New York State Code 405 and societal/political pressure have led the RRC
      and ACGME to mandate strict limitations on resident work hours. In an attempt to
      meet these limitations, we have switched from the previous Q3 call schedule to a
      specialized night float (NF) system, the continuity-care system (CCS). The
      purpose of this CCS is to maximize resident duty time spent on direct patient
      care, operative experience, and outpatient clinics, while reducing duty hours
      spent on performing routine tasks and call coverage. The implementation of the
      CCS is the fundamental step in the restructuring of our residency program. In
      addition to a change in the call system, we added physician assistants to aid in
      performing some service tasks. We performed a 360 degrees evaluation of this work
      in progress. METHODS: In May 2002, the standard Q3 call system was abolished on
      the general surgery services at the New York Presbyterian Hospital, Columbia
      campus. Two dedicated teams were created to provide day and night coverage, a day
      continuity-care team (DCT) and a night continuity-care team (NCT). The DCTs,
      consisting of PGY1-5 residents, provide daily in-house coverage from 6 AM to 5 PM
      with no regular weekday night-call responsibilities. The DCT residents provide
      Friday night, Saturday, and daytime Sunday call coverage 3 to 4 days per month.
      The NCT, consisting of 5 PGY1-5 residents, provides nightly continuous care, 5 PM
      to 6 AM, Sunday through Thursday, with no other weekend call responsibilities.
      This system creates a schedule with less than 80 duty hours per week, on average,
      with one 24-hour period off a week, one complete weekend off per month, and no
      more than 24 hours of consecutive duty time. After 1 year of use, the system was
      evaluated by a 360 degrees method in which residents, residents' spouses, nurses,
      and faculty were surveyed using a Likert-type scale. Statistical significance was
      calculated using the Student t-test. Patient satisfaction was measured both by
      internal review of a patient complaint database as well as by the Press Ganey
      patient satisfaction surveys. RESULTS: Twenty-one residents, 10 residents'
      spouses, 11 general surgery faculty, and 16 nurses were surveyed. Statistically
      significant findings included reduced resident fatigue noted by all groups
      (residents, p = 0.01; resident spouses, p = 0.05; faculty, p < 0.0001; nurses, p
      < 0.0001). Further, residents reported more time for sleep at home (p = 0.0005)
      and more time for independent reading (p = 0.01). Residents' spouses reported
      increased availability for family events (p = 0.01). Nurses reported increased
      availability of residents (p = 0.0002), shorter times to physician identification
      of patient problems (p = 0.0086), improved resident-nursing communications (p =
      0.0096), and increased ease of nursing duties (p < 0.0001). Faculty were the only
      responders who felt that continuity of patient care suffered with the new system
      (p = 0.02). The Press Ganey review showed improvement in the quality of care
      rendered as perceived by patients. CONCLUSIONS: The institution of a specialized
      NF or CCS for in-house coverage of general surgical services in a large
      metropolitan university hospital has had initial success in meeting the mandated
      changes in resident work hours. The CCS reduced resident fatigue, improved
      quality of resident life, and improved patient care as judged by patients and
      nurse.

PMID- 15475094
TI  - Do proton pump inhibitors increase the incidence of nosocomial pneumonia and
      related infectious complications when compared with histamine-2 receptor
      antagonists in critically ill trauma patients?
AB  - BACKGROUND: Proton pump inhibitors (PPI) may increase the risk of nosocomial
      pneumonia caused by profound irreversible gastric acid suppression. The study
      purpose was to characterize differences in nosocomial pneumonia and related
      infections in trauma patients administered either histamine2-receptor antagonists
      (H2RA) or PPI. METHODS: Observational evaluation of consecutive critically ill
      adult trauma patients administered either omeprazole or famotidine during a 22
      month period. Nosocomial infection was evaluated daily based on published CDC
      definitions. RESULTS: Eighty of 269 patients fulfilled study criteria. The PPI
      group (n = 40) exhibited increased baseline risk for infection, demonstrated by
      higher ISS (p = 0.020), more chest tube placements (p = 0.031), and increased
      chest trauma (p = 0.025). Overall number of patients infected per group included
      33% and 40% of patients administered PPI and H2RA, respectively (p = 0.64).
      Despite baseline differences, the incidence of nosocomial infection was similar
      (p = 0.87), and extrapolation of pneumonia based on 1000 patient days revealed a
      ratio 51.7 vs 52.2 in the PPI vs H2RA groups, respectively, which was not
      significant (p = 0.99). CONCLUSIONS: Proton pump inhibitor administration does
      not increase risk of nosocomial pneumonia or other nosocomial infections compared
      with H2RA therapy in the critically ill trauma patient.

PMID- 15475095
TI  - Fluid administration during abdominal surgery influences on coagulation in the
      postoperative period.
AB  - OBJECTIVE: Postoperative coagulopathy is an important concern for patients after
      major surgery. Our objective was to define the factors that correlate with
      postoperative deterioration in coagulation. DESIGN: Retrospective clinical case
      study. SETTING: University hospital. PARTICIPANTS: Adult patients (n = 150), who
      underwent major abdominal surgery, were randomly chosen to participate in the
      study. For each patient, demographic and medical data, anesthetic information,
      type and duration of surgery, hemodynamic variables, fluid administration, as
      well as preoperative and postoperative prothrombin time and partial
      thromboplastin time were collected. Statistical analysis was used to determine
      which factors correlated with deterioration of coagulation tests. RESULTS: We
      found statistically significant correlation between deteriorating coagulation
      functions and administration of more than 3 l of crystalloids during abdominal
      surgery. There was also correlation between administration of more than 500 ml of
      colloid administration and elongation of protrombin time. The remainder of the
      above studied factors did not correlate with deteriorating coagulation.
      CONCLUSIONS: Administration of more than 3-l crystalloids or 500-ml colloids
      during abdominal surgery correlates with postoperative coagulopathy.

PMID- 15475096
TI  - Negative pressure post-extubation pulmonary edema complicating appendectomy in a
      young patient: case report.
AB  - Negative-pressure pulmonary edema after endotracheal intubation is an uncommon
      and potentially serious complication of patients undergoing general anesthesia
      for different surgical procedures. We report a case of a healthy 20-year-old male
      patient with the diagnosis of acute appendicitis. The patient was submitted to
      appendectomy under general anesthesia and developed negative-pressure pulmonary
      edema immediately after extubation. The present paper reports this potentially
      serious complication illustrating the main radiological findings consistent with
      alveolar hemorrhage in this setting and the treatment performed.

PMID- 15475097
TI  - Twenty-first century surgery using twenty-first century technology: surgical
      robotics.
AB  - INTRODUCTION: The "Nintendo" surgery revolution, which began in 1987, has
      impacted every surgical specialty. However, our operating rooms remain isolated
      worlds where surgeons use awkward, primitive, rigid instruments with suboptimal
      visualization. We need "smart instruments," "smart technology," and "smart
      imaging." Is surgical robotics the answer? METHODS: We provide an analysis of
      current surgical technology and skills, propose criteria for what the next
      generation of surgical instruments and technology should achieve, and then
      examine the evolution and current state of surgical robotic solutions, assessing
      how they answer future surgical needs. Finally we report on the U.S. Military's
      early experience with surgical robotics and the lessons learned therein. RESULTS:
      Current surgical robotic technology has made remarkable progress with
      miniaturization, articulating hand-imitating instruments, precision, scaling, and
      three-dimensional vision. The specialty-specific early clinical applications
      reviewed are promising, but they do have limitations. Surgical robotics offers
      enormous military application potential. Needed future refinements are
      identified, including haptics, communications, infrastructure, and information
      integration. CONCLUSIONS: Laparoscopic surgery is a transition technology,
      constrained by instrument, equipment, and skill limitations. Surgical robotics
      or, more properly, computer-assisted surgery may be the key to the future. The
      operating room of the future will be an integrated environment with global reach.
      Surgeons will operate with three-dimensional vision, use real-time three
      dimensional reconstructions of patient anatomy, use miniaturized minimally
      invasive robotic technology, and be able to telementor, teleconsult, and even
      telemanipulate at a distance, thus offering enhanced patient care and safety.

PMID- 15475100
TI  - A little bit of religion helps the medicine go down.

PMID- 15475098
TI  - Victim of fashion: Endocarditis after oral piercing.
AB  - A case report of endocarditis after tongue piercing is presented. Body piercing
      is a form of self-expression that is achieving greater acceptance and wider
      practice in modern society. Even in healthy individuals, significant health risks
      exist with this type of physical adornment. Despite this fact, no significant
      regulatory mechanisms are currently in place to guide practitioners of this craft
      or to protect the recipients of body piercing. Medical professionals should join
      the American Dental Association in their opposition of the practice of
      intraoral/perioral piercing and should call for the development of legislation
      protecting the recipients of such practices, particularly the population of young
      people in whom this type of body art is becoming increasingly prevalent.

PMID- 15475101
TI  - Learning the spirituality of life and medicine from others.

PMID- 15475102
TI  - Wild life: Spirituality in medicine.

PMID- 15475103
TI  - The evolving Renaissance in surgical education.

PMID- 15475104
TI  - A program for successful integration of international medical graduates (IMGs)
      into U.S. surgical residency training.
AB  - OBJECTIVE: U.S. surgery residency programs have traditionally attracted
      international medical graduates (IMGs). However, the qualifications and
      performance of IMGs are variable and difficult to predict. Poor performance
      negatively affects patient care, the residency program, and the IMGs. We sought
      to identify causes of poor performance and to develop a program to identify those
      with chances to succeed. DESIGN: Longitudinal study. Retrospective analysis.
      Description of a new program. SETTING: University of Washington, a tertiary care
      teaching hospital. PARTICIPANTS: Performance of former IMG residents was reviewed
      to define the most common reasons for failure. In August 2002, we developed an
      IMG Certificate Program that enrolls IMGs into a formal 8-week clinical
      experience with duties, responsibilities, and evaluations similar to fourth-year
      medical students. A final global score is given for potential for success as a
      resident in our program. RESULTS: Poor performance in past IMG residents could be
      attributed to: credential problems and poor performance. Performance problems
      were further subdivided to include knowledge issues and personal/cultural issues.
      Since August 2002, our Certificate Program enrolled 15 IMGs. Fourteen graduated,
      and 10 were offered preliminary spots in our program: 4 are successful interns, 1
      returned to Italy, and 5 will start in 2004. One entered the 2004 match in
      Anesthesiology, and 1 was counseled to not be a candidate for a U.S. program.
      Three had above average performance and were felt to be better suited to a
      smaller program (1-2 hospitals). The mean "potential for success" global score
      was 3.9 (all grads), 4.6 (current interns), 1.0 (nongraduate), and 3.0 for the
      above average performers better suited to a smaller U.S. program. CONCLUSIONS: We
      developed a program that provides IMGs an 8-week clinical experience in a busy
      U.S. training program; it provides them with enough experience to successfully
      integrate into a U.S. residency and identifies those with better chances to
      succeed. Wide application of this program and exchange of information among
      program directors may facilitate recruitment and the successful completion of
      training of IMGs and provide the number of residents needed to fill critical
      positions in the United States.

PMID- 15475105
TI  - Beyond fulfilling the core competencies: an objective structured clinical
      examination to assess communication and interpersonal skills in a surgical
      residency.
AB  - OBJECTIVE: The Accreditation Council for Graduate Medical Education (ACGME) has
      challenged program directors to assess their residents' core competencies,
      including communication and interpersonal skills (CIS). We report our
      institution's experience using a series of standardized patient encounters in an
      objective structured clinical examination (OSCE) to evaluate CIS in surgical
      residents. METHODS: Standardized patients rated the residents' ability to
      maintain a patient-centered approach across 6 challenging communication tasks.
      Residents received verbal feedback from the patients after each encounter and
      completed a survey indicating their experience and comfort with each task.
      Individual and group reports documented resident competency and provided
      aggregate information for curriculum review. Formal grades were not assigned.
      RESULTS: Twenty-two residents in 2 surgical residency programs piloted the
      assessment. The Generalizability of the assessment was 0.81. Scores of second-
      and third-year residents were not significantly different. Residents found the
      program to be helpful and able to assess their skills. CONCLUSIONS: The
      standardized patient-based OSCE is an effective method to assess communication
      and interpersonal skills and provides useful information for curriculum review.

PMID- 15475107
TI  - The value of videotape in mock oral board examinations.
AB  - OBJECTIVE: To determine the impact on self-perception, of having residents view
      their own performance (taped) on mock oral board examinations. DESIGN: Self
      evaluation-intervention-self-evaluation design. Third-, fourth-, and fifth-year
      residents evaluated themselves after each examination(room) during mock oral
      examinations. Residents reviewed the examination on videotape and re-evaluated
      themselves. SETTING: University Medical Center. PARTICIPANTS: Twenty surgical
      residents from the third, fourth, and fifth years of training. MAIN OUTCOME
      MEASURES: Mean scores in 6 categories based on a 5-point Likert scale. Scores by
      examiners plus pre- and post-video viewing self-scores were compared. RESULTS: We
      found that residents consistently underestimated their performance on the
      examination. Viewing their videotapes resulted in revised self-scores, which were
      more consistent with scores of the examiners. All scores will be presented in
      sequence as follows: Mean score by examiners, mean self-score pre-tape viewing
      and mean self-score post-tape viewing. For professionalism, scores were 4.63,
      4.15, and 4.43, p = 0.047. For organization, 3.91, 3.27, and 3.63, p = 0.007. For
      decision making, 4.02, 3.42, and 3.72, p = 0.033. P-values reflect the comparison
      of resident self-scores pre- and post-tape viewing. Analysis of variance
      comparison of scores in various rooms (different examiners) revealed no
      significant difference in scores based on rooms (different examiners).
      Evaluations according to rooms (different examiners) were not statistically
      different, supporting inter-rater reliability. There was consistent improvement
      in knowledge and decision making with advanced years of training, supporting
      internal validity of the examination. CONCLUSIONS: Videotape viewing results in
      revised resident self-scores, which are more consistent with scores given by the
      examiners. Tape viewing significantly affected resident self-scores in
      professionalism, organization, and decision-making.

PMID- 15475106
TI  - Level of education and patient opinion: significant differences in perceptions of
      health care.
AB  - BACKGROUND: As part of the general competencies set forth by the Accreditation
      Council for Graduate Medical Education (ACGME), residents must have an
      understanding of systems-based practice, which is demonstrated by an awareness of
      and responsiveness to-the comprehensive health care system. Residents must be
      able to effectively access and use system resources to provide care that is of
      optimal value. Essential to understanding and implementing systems-based practice
      is an awareness of how different patient populations perceive health care; one
      key factor that influences patients' perceptions of health care is their level of
      education. METHODS: We surveyed 2900 adult patients in the Cincinnati, Ohio area
      and stratified them into 2 groups based on their level of education. Group 1
      included patients with some high school education or a high school degree. Group
      2 included patients with some college education, an undergraduate degree, or
      graduate/professional-level coursework. We then compared the groups' perceptions
      of common health care issues, including physician compensation, patient
      obligation for medical bills, and increased cost for the freedom to choose a
      physician. RESULTS: Of 395 respondents, a higher percentage of Group 2 patients,
      compared with those in Group 1, understood that physicians do not collect 100% of
      what they bill (p < 0.001) and that businesses do influence the amount a
      physician is paid by insurance companies (p = 0.009). Conversely, a higher
      percentage of Group 1 patients thought that physicians are overpaid (p = 0.030)
      and that they keep a large portion of what they charge (p < 0.001). Further,
      fewer Group 1 respondents felt obligated to pay medical bills not covered by
      insurance (p = 0.002); they also were less willing to pay more for better medical
      care (p = 0.002) or for the freedom to choose a physician (p = 0.015).
      CONCLUSIONS: This study indicates that patients with a lower level of education
      believe that physicians are overpaid and that they keep a large portion of
      insurance reimbursement. These findings may explain why fewer patients in this
      group feel that they are obligated to pay medical bills not covered by insurance
      and why they are less likely to pay more for better medical care or for the
      freedom to choose a physician.

PMID- 15475108
TI  - Noise amidst the silence: off-target effects of siRNAs?
AB  - RNA interference (RNAi), mediated by short interfering RNAs (siRNAs), is widely
      used to silence gene expression and to define gene function in mammalian cells.
      Initially, this gene silencing via transcript degradation was believed to be
      exquisitely specific, requiring near-identity between the siRNA and the target
      mRNA. However, several recent reports have suggested that non-specific effects
      can be induced by siRNAs, both at the level of mRNA and protein. These findings
      suggest that siRNAs can regulate the expression of unintended targets, and argue
      for further experiments on the mechanism and extent of off-target gene
      regulation(s). In the meantime, caution is warranted in interpreting gene
      function and phenotypes resulting from RNAi experiments.

PMID- 15475109
TI  - Chromosomal rearrangements and the genomic distribution of gene-expression
      divergence in humans and chimpanzees.
AB  - The genomic DNA sequences of humans and chimpanzees differ by only 1.24%.
      Recently, however, substantial differences in gene-expression patterns between
      the two species have been revealed. In this article, we investigate the genomic
      distribution of such differences. Besides confirming previous findings about the
      evolution of sex chromosomes and duplications, we show that chromosomal
      rearrangements are associated with increased gene-expression differences in the
      brain and that rearrangements can have both direct and indirect effects on the
      expression of linked genes. In addition, our results are consistent with a role
      for some rearrangements in the original speciation events that separated the
      human and chimpanzee lineages.

PMID- 15475110
TI  - Analysis of the centromeric regions of the human genome assembly.
AB  - The sequence of the human genome is not yet complete, and major gaps remain at
      the centromere region of each chromosome, which is comprised of repetitive alpha
      satellite DNA. In this article, we describe the sequences in the vicinity of the
      centromere that are included in the current genome assembly, analyze the
      approximately 7Mb of alpha satellite that have been assembled thus far and
      anticipate the nature of the sequences that remain to be accounted for.

PMID- 15475111
TI  - Evidence for codon bias selection at the pre-mRNA level in eukaryotes.
AB  - We investigated codon usage patterns across eukaryotic exons. We have shown that
      in humans codon preference varies with distance from the splice sites. This is
      consistent with the distribution of RNA elements involved in splicing regulation.
      Our results provide the first evidence that selection at the pre-mRNA level
      influences codon usage in humans. We also show that systematic trends in codon
      usage are found in other eukaryotes, suggesting that pre-mRNA level selection for
      codon usage could be a widespread phenomenon in organisms that undergo RNA
      splicing.

PMID- 15475112
TI  - New type of polyubiquitin-like genes with intein-like autoprocessing domains.
AB  - Genome analysis of ciliates identified a new type of polyubiquitin-like genes.
      These contain tandem repeats of ubiquitin-like domains interspersed with
      autocatalytic intein-like domains. Inteins and related protein domains post
      translationally process their own precursor proteins by protein-splicing,
      cleavage and ligation reactions. The structure of these polyubiquitin-like genes
      suggests their precursor products undergo maturation and conjugation in cis. This
      novel gene structure also illustrates the genetic modularity of ubiquitin-like
      and intein-like domains. Our suggested autoprocessing of ubiquitin-like
      polyproteins is a new potential general way for controlling protein functions.

PMID- 15475113
TI  - The altered evolutionary trajectories of gene duplicates.
AB  - Gene duplication is widely regarded as the predominant mechanism by which genes
      with new functions and associated phenotypic novelties arise. However, the
      mutational events and population-genetic mechanisms that lead to the short-term
      preservation of duplicate genes are not necessarily the same as those exhibited
      by well-established paralogs en route to the origin of new beneficial features.
      Thus, although recent genome-wide analyses have revealed striking patterns of
      protein-sequence divergence among the members of surviving paralogous gene
      families, the mechanisms responsible for the historical development of these
      patterns remain unclear.

PMID- 15475114
TI  - How the mouse got its spots.
AB  - One's ultimate phenotype is the result of a combination of genotype and
      environment, and includes a poorly understood component termed "developmental
      noise". This "developmental noise", also known as "intangible variation", is
      rarely discussed even though it appears to make a significant contribution to the
      variance of quantitative traits within a species. The molecular basis of
      developmental noise remains unknown, but it appears to be established in
      embryonic development and to be retained for the life of the organism. We propose
      that the molecular basis of developmental noise is, at least in some instances,
      the epigenetic state of the genome. The stochastic nature of the establishment of
      epigenetic state, combined with its heritability during mitosis, provides all of
      the essential components for developmental noise.

PMID- 15475115
TI  - Mitochondriomics or what makes us breathe.
AB  - Mitochondria perform several fundamental cellular processes in higher eukaryotes
      including oxidative phosphorylation, Fe/S cluster formation and apoptosis.
      Dysfunction of the organelle is associated with a wide range of human diseases.
      To gain a better understanding of mitochondrial function, several recent
      proteomic, genetic, transcriptomic and bioinformatic approaches have set out to
      determine the complete set of mitochondrially located proteins in yeast, plants
      and mammals. Here, we review these studies and discuss the advances and
      limitations of individual strategies. Integration of various approaches proves to
      be a successful and useful way to identify the mitochondrial proteome with high
      sensitivity and specificity. The most comprehensive dataset is available for
      Saccharomyces cerevisiae, giving an estimated number of 700 different proteins
      located in mitochondria.

PMID- 15475116
TI  - Evolution of the Fgf and Fgfr gene families.
AB  - Fibroblast growth factors (Fgfs) and Fgf receptors (Fgfrs) comprise a signaling
      system that is conserved throughout metazoan evolution. Twenty-two Fgfs and four
      Fgfrs have been identified in humans and mice. During evolution, the Fgf family
      appears to have expanded in two phases. In the first phase, during early metazoan
      evolution, Fgfs expanded from two or three to six genes by gene duplication. In
      the second phase, during the evolution of early vertebrates, the Fgf family
      expanded by two large-scale gen(om)e duplications. By contrast, the Fgfr family
      has expanded only in the second phase. However, the acquisition of alternative
      splicing by Fgfrs has increased their functional diversity. The mechanisms that
      regulate alternative splicing have been conserved since the divergences of
      echinoderms and vertebrates. The expansion of the Fgf and Fgfr gene families has
      enabled this signaling system to acquire functional diversity and, therefore, an
      almost ubiquitous involvement in developmental and physiological processes.

PMID- 15475117
TI  - Van Gogh-like2 (Strabismus) and its role in planar cell polarity and convergent
      extension in vertebrates.
AB  - In the past two years, studies of Stbm genes (also known as Vangl2) and the
      proteins that they encode in mice, flies, frogs and fish have shown that they
      have a crucial role in regulating planar cell polarity and convergent extension
      movements. Combined genetic and biochemical analyses have pointed to signaling
      pathways where Stbm (Vangl2) proteins might act, and have identified several
      interacting proteins that form a crucial multi-protein signaling complex at the
      membrane. These studies show that these proteins have a pivotal role in a
      signaling cascade(s) that has been highly conserved in evolution. This review
      will summarize recent findings documenting the involvement of Stbm (Vangl2) and
      associated proteins in planar cell polarity, non-canonical Wnt signaling and
      convergent extension movements.

PMID- 15475118
TI  - Accelerated evolution of the electron transport chain in anthropoid primates.
AB  - Mitochondria are both the power plant of the cell and a central integrator of
      signals that govern the lifespan, replication and death of the cell. Perhaps as a
      consequence, genes that encode components of the mitochondrial electron transport
      chain (ETC) are generally conserved. Therefore, it is surprising that many of
      these genes in anthropoid primates (New World monkeys, Old World monkeys and
      apes, including humans) have been major targets of darwinian positive selection.
      Sequence comparisons have provided evidence that marked increases of non
      synonymous substitution rates occurred in anthropoid ETC genes that encode
      subunits of Complex III and IV, and the electron carrier molecule cytochrome c
      (CYC). Two important questions are: (i) how has evolution altered ETC function?
      and; (ii) how might functional changes in the ETC be linked to evolution of an
      expanded neocortical brain?

PMID- 15475119
TI  - Artificial neural networks in motor control research.

PMID- 15475120
TI  - Applications of artificial neural nets in clinical biomechanics.
AB  - The purpose of this article is to provide an overview of current applications of
      artificial neural networks in the area of clinical biomechanics. The body of
      literature on artificial neural networks grew intractably vast during the last 15
      years. Conventional statistical models may present certain limitations that can
      be overcome by neural networks. Artificial neural networks in general are
      introduced, some limitations, and some proven benefits are discussed.

PMID- 15475121
TI  - Cervical muscle response to posterolateral impacts--effect of head rotation.
AB  - BACKGROUND: Rear impacts may be offset, and may also occur with the head rotated
      at impact. The purpose of this study was to determine the response of the
      cervical muscles to increasing low-velocity rear impacts offset by 45 degrees to
      the subject's right, but also with the head rotated either right or left.
      METHODS: Twenty healthy volunteers underwent right posterolateral impacts of 4.6,
      8.0, 11.0, and 13.1 m/s2 acceleration with head turned right or left.
      Electromyograms of the sternocleidomastoids, trapezii, and splenii capitis were
      recorded, as were acceleration of the sled, torso, and head of the participant.
      FINDINGS: At an impact acceleration of 13.1 m/s2, with head rotated to the right,
      the left sternocleidomastoid and the contralateral (to rotation) trapezius and
      splenius capitis generated more electromyogram activity than their counterparts
      (P < 0.05). Following impacts with the head rotated to the right, the left
      sternocleidomastoid generated 67% of its maximal voluntary electromyogram, and
      the right sternocleidomastoid 5% of the maximal voluntary electromyogram, whereas
      the remaining muscles did not generate more than 31% of the maximal voluntary
      contraction electromyogram. In impacts with head rotated left, the right
      sternocleidomastoid generated 53% of its maximal voluntary electromyogram, and
      the left splenius capitis and left trapezius showed more electromyogram activity
      than their counterparts (P < 0.05). INTERPRETATION: Head rotation in a right
      posterolateral impact modifies the cervical response mainly by generating an
      asymmetry in the paired sternocleidomastoid electromyograms. This may
      asymmetrically affect the risk of injury to the sternocleidomastoids. An
      understanding of the muscular response to rear-impacts of different types and the
      effect of head rotation at the time of impact is relevant to understanding the
      mechanism of acute whiplash injury and may be helpful to develop targeted
      treatments and preventative measures.

PMID- 15475122
TI  - Biomechanical analysis of scapular neck malunion--a simulation study.
AB  - OBJECTIVE: To explain loss of shoulder function following scapular neck malunion
      in terms of biomechanical changes around the gleno-humeral joint. DESIGN:
      Biomechanical modelling study. BACKGROUND: Residual rotation of the scapular neck
      after fracture can lead to pain and loss of function, and the indications for
      surgical intervention are contested. METHODS: A 3D, large-scale, musculo-skeletal
      model of the upper limb was used to compare shoulder biomechanics in the case of
      scapular neck malunion with normal anatomy. Abduction of the humerus was
      simulated with three models: normal anatomy, 24 degrees and 40 degrees inferior
      scapular neck rotation. RESULTS: Predicted muscle activation differed greatly
      between the control and the fracture cases. The motion required additional muscle
      effort for the maintenance of gleno-humeral stability in the fracture cases.
      Higher moments in the plane of abduction were generated by the teres major,
      pectoralis major and biceps brachii muscles with high humeral elevation angles.
      The rotator cuff muscles were severely shortened in the post-fracture cases and
      the forces in these muscles were greatly reduced in a test of loaded abduction
      with the humerus at 90 degrees. CONCLUSIONS: Given the function of the rotator
      cuff muscles as stabilisers of the gleno-humeral joint, it is concluded that the
      loss of force in these muscles, together with other changes in muscle activation,
      will lead to loss of arm function in patients with scapular neck malunion.
      RELEVANCE: These findings will contribute to the improved treatment of patients
      with scapular neck malunion by identifying important factors in the consideration
      of surgical intervention.

PMID- 15475123
TI  - Reliability of force direction dependent EMG parameters of shoulder muscles for
      clinical measurements.
AB  - OBJECTIVE: To assess the reliability of force direction dependent EMG parameters
      in shoulder muscles for future clinical research. DESIGN: EMG measurements of
      shoulder muscles including the rotator cuff were performed during isometrical
      external loading in various directions covering 360 degrees in a plane
      perpendicular to the humeral axis. BACKGROUND: Relating EMG to force direction
      bypasses problems associated with the unknown position and velocity dependence of
      the EMG signal. For clinical application, information on the reliability of force
      direction dependent parameters is required. METHODS: The EMG of shoulder muscles
      of healthy subjects was related to force direction. The activation patterns
      obtained where parameterised after least squares function fitting, returning
      three force direction dependent parameters, i.e. two on- and offset directions of
      the activity peak and the direction of highest EMG activity also called principal
      action. Within-trial, inter-trial, inter-day and inter-subject variabilities were
      estimated. RESULTS: With a group size of n = 10, the 95% confidence interval for
      inter-day measurements was found to be about +/-5 degrees on a scale of 360
      degrees for the principal action and just below +/-10 degrees for the intercepts.
      CONCLUSION: The method allows for intra-individual measurements on different days
      with sufficient accuracy so that shoulder muscle co-ordination of patients before
      and after interventions like surgery or physical therapy can be evaluated.
      RELEVANCE: Quantitative data on shoulder muscle function in vivo are required to
      assess the effectiveness of interventions on the shoulder.

PMID- 15475124
TI  - Upper limb mechanical changes following short duration repetitive eccentric
      exertions.
AB  - BACKGROUND: Power hand tool use is considered a risk factor for upper extremity
      musculoskeletal disorders. It is unclear if submaximal eccentric activity
      inherent to power tool use adversely affects the mechanical properties of muscle.
      METHODS: This study investigated in vivo changes in human upper limb dynamic
      mechanical properties following exposure to short-term repetitive submaximal
      eccentric exertions that are similar to operating an industrial power hand tool.
      Eighteen subjects (12 males and 6 females) were assigned to one of three exercise
      groups (isometric, eccentric or control) and exercised 10 min for 60 repetitions
      at 50% of isometric forearm supination maximum voluntary contraction. Supination
      strength and dynamic mechanical properties (stiffness, effective mass, and
      damping) of forearm rotation, modeled as a single-degree-of-freedom system during
      maximal exertion, were ascertained prior to exercise, immediately following
      exercise and 24 h later. FINDINGS: Strength decreased for the isometric (17%) (P
      < 0.05) and eccentric (34%) (P < 0.01) groups following exercise. Only the
      eccentric exercise group had a reduction in mechanical stiffness (53%) (P < 0.01)
      and effective mass (58%) (P < 0.05). The other groups had no changes in
      mechanical properties. INTERPRETATION: The change in mechanical properties
      following repetitive submaximal eccentric activity could negatively impact the
      ability of the arm to react to rapid forceful loading during repetitive
      industrial work activities and may indicate mechanical strain on the upper limb.

PMID- 15475125
TI  - Muscular effort in multiple sclerosis patients during powered wheelchair
      manoeuvres.
AB  - BACKGROUND: This study applied EMG analysis methods to identify muscle group
      activity profiles and potential overload risks in powered wheelchair use.
      METHODS: We quantified muscle effort and fatigue using EMG analysis methods
      during powered wheelchair manoeuvres by 10 multiple sclerosis patients. Video
      recordings of the different sub-tasks were related to information on surface EMG
      amplitude (rectified EMG) and spectral information (Median frequency) from M.
      trapezius, M. deltoideus (pars medius), M. deltoideus (pars anterior), M.
      pectoralis, M. biceps, M. triceps, wrist extensors and flexors, using Joint
      Analysis of EMG Spectrum and Amplitude (JASA analysis). FINDINGS: Task durations
      and subjective data indicated that tasks requiring finer motor control took
      longer and were perceived as more difficult. Kinesiological functions of all
      muscle groups identified forward steering to be associated with activation of M.
      deltoideus (pars anterior), M. pectoralis, M. trapezius and M. deltoideus (pars
      medius); backwards steering with predominant activation of M. deltoideus (pars
      medius), M. biceps brachii and wrist flexors; left steering with maximal
      activation of M. biceps and wrist flexors, and right steering with maximal
      activation of M. triceps and wrist extensors. These profiles were confirmed in
      analysis of the functional tasks. JASA analysis documented muscle fatigue in the
      wrist extensors, whereas increased activation was found in M. trapezius, M.
      deltoideus (pars anterior) and wrist flexors. INTERPRETATION: EMG based
      kinesiological analysis gives insight in muscle activity and fatigue during
      powered wheelchair manoeuvres.

PMID- 15475126
TI  - High contact hip stress is related to the development of hip pathology with
      increasing age.
AB  - BACKGROUND: High contact hip stress is believed to be one of the key
      biomechanical factors involved in the hip cartilage degeneration and
      osteoarthritis. Accordingly, with increasing age high contact hip stress is
      expected to cause elimination of subjects from the population of healthy hips,
      but its predictive value has not been evaluated so far. The objective of the
      paper is to investigate whether the exposure of healthy hips to estimated high
      contact hip stress is related to the development of hip pathology with increasing
      age. METHODS: A cross-sectional age- and gender-matched analysis of the peak
      contact hip stress calculated from pelvic geometry was made in 103 adult subjects
      with healthy hips. The peak contact hip stress was calculated from anterior
      posterior pelvic radiographs of healthy hips by using a mathematical model of the
      human hip in the static one-legged stance. FINDINGS: In both female and male
      population, the average values of the peak contact hip stress normalized to the
      body weight are significantly higher and the values are also more dispersed in
      younger subjects when compared to older subjects. INTERPRETATION: The hip joints
      which remain healthy in the old age have lower average estimated peak contact hip
      stress. These results are consistent with the explanation that subjects with high
      estimated peak contact hip stress are more likely to develop hip disease in the
      course of life.

PMID- 15475127
TI  - Open wedge high tibial osteotomy: biomechanical investigation of the modified
      Arthrex Osteotomy Plate (Puddu Plate) and the TomoFix Plate.
AB  - OBJECTIVE: To determine the biomechanical properties of different fixation
      methods for high tibial medial opening wedge osteotomy in order to determine
      appropriate surgical and rehabilitation guidelines. DESIGN: A biomechanical
      testing examined the construct stiffness and the fixation strength of two
      different plates. BACKGROUND: Although medial opening wedge techniques for high
      tibial osteotomies have become popular in recent years, biomechanical data of
      frequently used implants is lacking. METHODS: A 15-mm medial opening gap was
      stabilized in each of eight medium composite tibial bones either with the
      modified Arthrex Osteotomy Plate (Puddu Plate) or the TomoFix Plate. RESULTS:
      Both constructs failed under compression and torsion at the lateral cortex and
      occurred at higher maximal forces by using the TomoFix Plate. After fracture of
      the lateral cortex the axial stiffness was reduced by 47% and the torsional
      rigidity by 54% for the TomoFix. For the Puddu Plate these reductions were 66%
      and 78%, respectively. The differences between the two groups were significant in
      all conducted tests (P < 0.05). CONCLUSIONS: This study indicates that an
      unharmed lateral hinge largely dictates the stability after high tibial
      osteotomy. If the lateral cortex is injured, the TomoFix plate provides superior
      stability in both compression and torsion compared to the Puddu Plate. In the
      latter case additional fixation might be considered. RELEVANCE: These
      biomechanical tests helped to identify clinical situations in which the
      mechanical attributes of the plates would prove advantageous.

PMID- 15475128
TI  - The effect of tibial insert design on rising from a chair; motion analysis after
      total knee replacement.
AB  - BACKGROUND: There are few previous studies of sit-to-stand movement following
      total knee arthroplasty. Aim of the study was to test the hypotheses that total
      knee replacement alters the maximum trunk, hip, knee and ankle flexion-extension
      movements during chair rising, and that the design of the tibial plateau has
      small influence on the kinematics. METHODS: A motion analysis system was used to
      evaluate kinematics of the trunk, hip, knee and ankle when rising from one chair
      and sitting down on another. Patients with 5 degrees varus/valgus alignment or
      less received either a flat or a concave tibial insert with retention of the
      posterior cruciate ligament. Patients who had more malalignment and /or extension
      defect of 10 degrees or more were randomized to receive the concave or a
      posterior-stabilized tibial component with resection of the posterior cruciate
      ligament. The two groups of patients operated with and without resection of the
      posterior cruciate ligament were analysed separately and compared with a control
      group. 28 patients (29 knees) and 16 controls were in the final analysis.
      FINDINGS: Decreased hip and knee extension compared to the controls was seen, but
      there were no statistically significant differences in kinematics between the
      designs. INTERPRETATION: Choice of implant design in total knee arthroplasty had
      no detectable effects on kinematics of hip and knee joints during sit-to-stand
      movement.

PMID- 15475129
TI  - The effect of the walking speed on the stability of the anterior cruciate
      ligament deficient knee.
AB  - BACKGROUND: The reasons behind the development of future pathology in individuals
      with anterior cruciate ligament deficiency are unknown. This is due to the lack
      of appropriate methods to assess functional dynamic knee stability. In this
      study, we investigated the effect of walking speed on the functional dynamic
      stability of the anterior cruciate ligament deficient knee. We defined functional
      dynamic stability as local stability or the sensitivity of the knee to small
      perturbations. The natural stride-to-stride variations that exist during
      locomotion reflect exactly the presence of these perturbations. We hypothesized
      that speed will affect local stability in the deficient knee, especially when
      compared with the contralateral intact. METHODS: Ten subjects with unilateral
      deficiency walked on a treadmill at their self-selected speed, 20% faster, and
      20% slower, while kinematic data were collected (50 Hz) for 100 consecutive
      footfalls for each condition. The largest Lyapunov Exponent of the resulted knee
      joint flexion-extension time series was calculated to quantify local stability.
      FINDINGS: The deficient knee was significantly more locally unstable than the
      contralateral knee. Furthermore, increases in walking speed did not affect local
      stability for our subject population. INTERPRETATIONS: The altered local
      stability may render the deficient knee less adaptable to the ever-changing
      environmental demands. This may explain the increased future pathology found in
      these knees. However, future efforts should attempt to evaluate this speculation
      using longitudinal studies. We also propose that the tools utilized in this study
      can be used eventually to assess functional dynamic knee stability in clinical
      gait analysis.

PMID- 15475130
TI  - The effects of ankle bracing on motion of the knee and the hip joint during trunk
      rotation tasks.
AB  - BACKGROUND: The use of prophylactic ankle braces is common during athletic
      activities since the ankle is one of the most commonly injured joints. Past
      studies have focused on the effects of ankle braces on ankle movement
      restriction, preventing injuries, proprioception, balance and athletic
      performance. However, the influence of ankle restriction on other joints has not
      been studied. The constraint of ankle movement may lead to an increased loading
      on the knee joint, which could be a potential risk of knee injuries during
      athletic activities. The primary goal of the current study was to determine
      quantitatively the effect of an ankle brace on the knee axial rotation during two
      different trunk turning tasks. METHODS: Ten healthy subjects performed trunk
      turning movements while standing on one leg: turning sideways to catch a ball and
      turning sideways to touch a target with the shoulder. The tasks were performed
      with and without an ankle brace worn on the supporting leg. The trunk axial
      rotation in reference to the floor and three dimensional joint angular motions of
      the ankle, knee and hip were determined. FINDINGS: The use of an ankle brace
      resulted in reduced trunk axial rotation during the ball catching tasks, and
      increased knee axial rotation during the target touching tasks. INTERPRETATION:
      The results of this study showed that the effect of the ankle brace on the knee
      axial rotation depended on the context of the tasks performed. Under situations
      that required forceful trunk turning movement while standing on a single leg, the
      ankle braces may cause an increase in the knee axial rotation indicating higher
      risk of knee injury.

PMID- 15475131
TI  - The effect of simple insoles on three-dimensional foot motion during normal
      walking.
AB  - BACKGROUND: The purpose of this study was to establish the effect of simple non
      moulded flat based insoles on three-dimensional foot motion during normal
      walking. Excessive foot pronation is considered a major contributing factor to
      lower limb injuries. Moulded foot orthoses have been shown to decrease maximum
      foot eversion. Simple insoles are widely used in clinical practice as an
      alternative to moulded orthoses. However, there has been little research into the
      kinematic effects of simple insoles. METHODS: All subjects had an inverted
      rearfoot and forefoot position when the subtalar joint was placed in neutral,
      which was assessed by a weight bearing goniometer. Rotations of the whole foot
      about three orthogonal axes relative to the shank were estimated using a five
      camera motion analysis system. FINDINGS: Biplanar insoles significantly (P <
      0.05) reduced maximum eversion by an average of 3.1 degrees when compared to the
      no insole condition. The cobra insole reduced maximum eversion by an average of
      2.1 degrees when compared to the no insole condition. This difference approached
      statistical significance (P = 0.058). INTERPRETATION: Biplanar and cobra insoles
      had no significant effect on maximum dorsiflexion, abduction or rate of eversion,
      when compared to the no insole condition. These results provide some limited
      support for the use of simple insoles to control for excessive foot pronation
      during walking.

PMID- 15475132
TI  - Biomechanical differences in landing with and without shoe wear after anterior
      cruciate ligament reconstruction.
AB  - OBJECTIVE: To determine biomechanical differences during single limb landing
      performed with and without shoe wear in anterior cruciate ligament reconstruction
      subjects. DESIGN: Barefoot and shod conditions were compared for both operated
      and contralateral limbs. BACKGROUND: Biomechanical analysis has been used to
      better understand the functional changes associated with anterior cruciate
      ligament reconstruction. However, no studies have investigated whether routine
      testing of patients should be performed barefoot or shod. METHODS: A three
      dimensional motion analysis and force plate system were used to obtain kinematic
      and kinetic data from eight anterior cruciate ligament reconstruction subjects
      during single-limb landings from a 15 cm vertical height. RESULTS: Peak knee
      flexion angles and moments were significantly reduced during barefoot testing in
      all eight subjects for the operated limb only (p < 0.01). The differences were
      however small; mean angular difference 3 degrees and mean moment difference 0.2
      Nm/kg. Knee flexion angles at initial contact and peak vertical ground-reaction
      forces were not affected by shoe wear. CONCLUSIONS: These results show that shoe
      wear does affect some biomechanical variables on landing but not so as to affect
      comparisons between operated and contralateral limbs. RELEVANCE: Given the
      comparable results between conditions, biomechanical testing following anterior
      cruciate ligament reconstruction can be performed either barefoot or shod.
      Testing subjects barefoot has the advantage of easier marker placement, and
      alleviates the need for shoe wear standardization.

PMID- 15475133
TI  - Host defense peptides in burns.
AB  - Overuse of antibiotics and failure to apply basic infection control policies and
      procedures have contributed to the increasing multi-drug resistance of many
      nosocomial pathogens. The alarming increase of multi-drug-resistant bacteria
      (e.g. Pseudomonas aeruginosa, methicilin-resistant Staphylococci, vancomycin
      resistant Enterococci) causes infected wounds associated with high mortality and
      morbidity in burned patients and focuses attention on the need for better
      treatment and prevention of wound infections. The review points out and discusses
      some emerging alternatives to antibiotics used in clinical practice, with special
      emphasis on the role of the innate immune response and potential application of
      human host defense peptides in thermal injury.

PMID- 15475134
TI  - Intentional burn injury: an evidence-based, clinical and forensic review.
AB  - Burn injury can be inflicted intentionally either by one person to another
      whenever one has the ability to physically control the other, or it can be self
      inflicted. There is scant evidential basis for much that is written about and
      practiced in the evaluation and care of patients that have sustained intentional
      burn injuries. Yet this is an area in which medical personnel must necessarily be
      trained in both the therapeutic and forensic aspects of a complex problem.
      Failure to appreciate the complexity of medical and forensic interactions may
      have far reaching effects. A missed diagnosis can result in inappropriate medical
      care, on-going abuse and future fatality. Inept management can result on the one
      hand, in blame levelled inappropriately placing incomparable strain on family
      units and innocent parties, and on the other, allow abusers to continue
      unchecked. This is the first review on the subject in which lawyers and doctors
      collaborate to produce a holistic approach to this subject. In it we describe the
      legal considerations that medical staff must appreciate when approaching patients
      who may have suffered intentional burns. We analyse the various scenarios in
      which intentional burning can be found and challenge the clinical dogma with much
      of the management of paediatric inflicted burns has become imbued. We suggest a
      rational and balanced approach to all intentional burn injuries-especially when
      children are involved. In the light of current case law in which dogmatic medical
      evidence has been implicated in wrongful convictions for child abuse in the UK,
      it is imperative that medical professionals gather evidence carefully and
      completely and apply it with logic and impartiality. This paper will aid
      clinicians who may not be experienced in dealing with burn injuries, but find
      themselves in the position of seeing a burn acutely, to avoid common mistakes.

PMID- 15475135
TI  - Expression of human beta-defensins HBD-1, HBD-2, and HBD-3 in cultured
      keratinocytes and skin substitutes.
AB  - Defensins are effector molecules of the innate host defense system with
      antimicrobial activity against a variety of pathogens, including microorganisms
      commonly found in burn units. beta-Defensins are variably expressed in the
      epithelia of skin and other organs. Cultured skin substitutes (CSS) grafted to
      burn wounds lack a vascular plexus and are therefore more susceptible to
      microbial contamination than split thickness skin autograft. To investigate
      whether beta-defensins can contribute to host defense in CSS, we examined
      expression of human beta-defensins HBD-1, HBD-2, and HBD-3 in cultured
      keratinocytes and CSS from uninjured donors and burn patients. HBD-1 was
      expressed in all keratinocyte strains analyzed. HBD-2 expression in keratinocyte
      monolayers was highly variable but did not correlate with burn injury. HBD-3 was
      expressed at variable levels in all but one keratinocyte strain. CSS were
      prepared from two donors that lacked expression of HBD-2 in keratinocyte
      monolayers. All three genes were readily detected in CSS from both donors,
      suggesting up-regulation of HBD-2 and HBD-3. In sections of CSS, HBD-1, HBD-2,
      and HBD-3 proteins were localized to distinct epidermal regions. We conclude that
      beta-defensins can potentially contribute to innate immunity in CSS, but their
      levels may be too low to prevent contamination after grafting.

PMID- 15475136
TI  - Expression of human beta defensin 2 in thermal injury.
AB  - Sepsis is a common and serious complication of major burn injury and accounts for
      over 54% of deaths in burn patients. Burns are associated with high levels of
      circulating pro-inflammatory cytokines and immunosuppression, promoting systemic
      inflammatory response syndrome (SIRS) and sepsis, for which no effective
      treatment is currently available. Defensins, a family of cationic, naturally
      occurring, antimicrobial peptides are important components of the innate immune
      system, playing a major role in the body's defence by inhibiting activities of
      bacteria, fungi and enveloped viruses. These natural antimicrobials also
      chemoattract immature dendritic cells, some types of T and B-lymphocytes,
      neutrophils and macrophages, and act as an adjuvant, enhancing adaptive immunity.
      Our prior studies suggested a decreased expression of human beta defensin 2
      (HBD2) in burn wounds. Here we have identified HBD2 protein in skin samples of
      partial and full thickness burns and in normal skin using fluorescence
      deconvolution microscopy. Images showed that in normal skin the majority of HBD2
      is located in the Malpighian layer and, in smaller amounts, in the more
      superficial layers, a pattern that is absent in burned skin in which the
      epidermis is destroyed or damaged. However, surviving dermal and subcutaneous
      layers revealed the presence of HBD2 in a number of other cell types and
      structures, such as hair follicles and sweat gland acini, but not in vascular
      endothelium and fat cells. The results of these studies further contribute to an
      understanding of the role of antimicrobial peptides in the pathophysiology of
      burn injury, associated immunosuppression and sepsis and the possibility of using
      these other sites of HBD2 deposition for upregulation of antimicrobial synthesis
      in the treatment of burns.

PMID- 15475137
TI  - International society for burn injuries survey: infection and infectious
      complications in worldwide burn units.

PMID- 15475138
TI  - The time-related changes of antimicrobial resistance patterns and predominant
      bacterial profiles of burn wounds and body flora of burned patients.
AB  - To examine the bacterial isolates from the burn patients and to compare the
      antibiograms of the predominant bacteria isolated from 51 patients who were
      hospitalized at least 3 weeks or more over a period of 7 months, a prospective
      study was undertaken. Periodic swabs were taken from burn wound, nasal, axillary,
      inguinal, and umbilical region of the patients on admission and on 7th, 14th, and
      21st days of hospitalization. Mean hospital stay was 36.5 days. A total of 1098
      microbial isolates were detected during the study period. Coagulase-negative
      staphylococci (CNS, 63.0%) and Staphylococcus aureus (19.7%) were the most
      prevalent isolates in admission cultures. During the next weeks, these bacteria
      were superceded by mainly Pseudomonas aeruginosa. Between admission and 21st day,
      the rates of methicillin resistance of staphylococci strains increased steadily.
      There was no vancomycin resistance in any staphylococci strains, although nine of
      the S. aureus isolates (2.7%) were resistant to teicoplanin. There were no
      strains producing inducible beta lactamase (IBL) among P. aeruginosa strains. One
      extended-spectrum beta-lactamase (ESBL)-producing strain was recovered on
      admission, although strains producing IBL and ESBL were detected at rates of 79.6
      and 57.1%, respectively, on the 21st day. The nature of microbial wound
      colonization, flora changes, and antimicrobial sensitivity profiles should be
      taken into consideration in using empirical antimicrobial therapy of burned
      patients.

PMID- 15475139
TI  - A prospective study of hospital-acquired infections in burn patients at a
      tertiary care referral centre in North India.
AB  - A prospective study was carried out in a burn unit of a tertiary care referral
      centre in North India. Patients with 20-70% TBSAB were enrolled. Seventy-one
      patients developed 59 hospital-acquired infections (HAI); the infection density
      being 36.2 infections per 1000 patient days. Invasive wound infections were the
      commonest (33), followed by blood stream infections (22), urinary tract
      infections (3) and pneumonia (1). Infection contributed to 75% of observed
      mortality. On logistic regression analysis, infected patients were more likely to
      die as well as stay longer in the hospital as compared to non-infected patients.
      Infected patients also had more central venous lines inserted. The mortality was
      related to percent TBSAB. Thirteen out of 18 patients who had TBSAB more than 60%
      died as compared to 5 out of 31 with TBSAB less than 40%. Staphylococcus aureus,
      Pseudomonas aeruginosa and beta-hemolytic streptococci (BHS) were the most
      frequent organisms causing hospital-acquired infection. Except for BHS all other
      organisms were highly drug resistant. Better compliance with hand washing and
      barrier nursing techniques, stricter control over disinfection and sterilization
      practices and usage of broad spectrum antibiotics, and reduction of the
      environmental contamination with S. aureus are required to reduce the HAI rates.

PMID- 15475140
TI  - Immune response in burn patients in relation to HIV infection and sepsis.
AB  - The post-burn immune dysfunction predisposes patients to sepsis and multiple
      organ failure leading to increased mortality. HIV infection also results in a
      depressed immune response. The combination of burn injury and HIV might therefore
      lead to an increased morbidity and mortality as compared to non-HIV infected burn
      patients. Twenty burn patients and 10 healthy volunteers were included in a
      prospective study. To evaluate their immune status, CD4+ and CD8+ T-lymphocyte
      counts were determined in peripheral blood. HIV serology samples were obtained on
      admission. Bacteriological cultures were obtained from wound surface samples and
      wound tissue biopsies. Six burn patients were HIV infected. Clinical signs of
      sepsis were observed in 10 patients. The number of CD4+ T-lymphocytes were lower
      in burn patients compared to healthy volunteers (P < 0.05). HIV infected burn
      patients had lower CD4+ lymphocyte counts than non-HIV infected patients (P <
      0.05). Patients with clinical signs of sepsis had lower CD4+ counts compared to
      patients without sepsis (P < 0.05). There was no difference in the mortality rate
      or the length of hospitalisation between patient groups. Burn injury, HIV
      infection and sepsis independently result in immunosuppression.

PMID- 15475141
TI  - Recovery from the hepatic acute phase response in the severely burned and the
      effects of long-term growth hormone treatment.
AB  - BACKGROUND: Administration of growth hormone (GH) to burned children decreases
      acute phase proteins and increases constitutive proteins when used during the
      acute hospitalization. Treatment during convalescence has not been examined.
      METHODS: Seventy-six children with total body surface area burned (TBSAB) >/=40%
      were randomized to either placebo or GH (0.05 mg/kg/day) from discharge to 1 year
      after burn. Subjects were followed for an additional year. Levels of constitutive
      proteins and acute phase proteins were measured at discharge and 6, 9, 12, 18,
      and 24 months. Data are expressed as mean +/- S.E.M. RESULTS: Albumin and
      transferrin levels increased during convalescence to the normal range but pre
      albumin and retinol binding protein (RBP) levels remained below normal for at
      least 24 months. Acute phase proteins alpha(1)-acid glycoprotein, C-reactive
      protein, and haptoglobin decreased (P < 0.05) but alpha(2)-macroglobulin
      increased from discharge to 6 months. C-3 complement remained elevated for at
      least 2 years after burn. Changes were similar in both groups with no effect for
      GH treatment. CONCLUSION: Some hepatic acute phase and constitutive proteins
      remain abnormal even 2 years after injury. GH treatment during convalescence has
      no effect on hepatic acute phase protein changes.

PMID- 15475142
TI  - Correlation between serum creatinine kinase levels and extent of muscle damage in
      electrical burns.
AB  - The relationship between clinical course and changes of laboratory findings in
      patients with high-voltage electrical burns with regard to creatinine kinase
      activity was analyzed in order to determine the value of this prognostic
      parameter with regard to patients survival and risk of limb amputation. In a
      retrospective study 42 patients with electrical burns were reviewed. CK serum
      levels were determined every day during the first 10 days following submission.
      Analysis of data revealed a relation between strongly elevated CK levels and
      patients risk of limb amputation and mortality. Although further research is
      necessary, there is strong evidence that the amount of burned body surface area
      does not directly correlate with the true extent of tissue damage caused by high
      tension injuries. Our data suggest that the degree of muscle tissue violation
      corresponds with the initial excess of creatinine kinase levels in blood serum.
      This may be an additional factor to support the decision for early surgical
      decompression of electrically burned extremities and aggressive surgical
      management of the high-voltage burn victim. Furthermore, it may provide a
      prognostic parameter for the clinical outcome of these patients.

PMID- 15475143
TI  - The progression of burn depth in experimental burns: a histological and
      methodological study.
AB  - This study was designed to create a reproducible model for experimental burn
      wound research in pigs. Previously, the thicker paraspinal skin has been used. We
      used the more human-like ventral skin to create burns of different depths.
      Contact burns were created to 11 pigs using a brass plate heated to 100 degrees C
      in boiling water. Different contact times were used to create burns of different
      depths. In pigs 1-6, the follow-up time was 72 h and in pigs 7-11 24 h. Burn
      depth was determined by histology. Histologically, samples were classified into
      five anatomical layers: epidermis, upper one-third of the dermis, middle third of
      the dermis, deepest third of the dermis and subcutaneous fat. The location of
      both thromboses and burn marks were evaluated, respectively. The 1 s contact time
      lead to a superficial thermal injury, 3 s to a partial thickness and 9 s to a
      full thickness injury. A progression of burn depth was found until 48 h post
      injury. The intra-observer correlation after repeated histological analyses of
      burn depths by the same histopathologist and the repeatability of burn depth
      creation yielded kappa coefficients 0.83 and 0.92, respectively. CONCLUSION: a
      reproducible burn model for further research purposes was obtained.

PMID- 15475144
TI  - Delayed spinal cord injury following electrical burns: a 7-year experience.
AB  - Although delayed spinal cord injury following high-voltage electrical burn is not
      a life-threatening sequelae, complete recovery is not the rule and the morbidity
      is high. In this study, we conducted a detailed analysis of clinical
      characteristics, radiographic findings and clinical outcomes in 13 patients with
      delayed spinal cord injury following electrical burns. The following features
      were notable. In 11 patients whose entry sites were the head and neck area,
      paraplegia was detected in cases whose exit sites were lower extremity only,
      while quadriplegia or cervical injury pattern EMG findings were observed in cases
      whose exit sites were upper extremity. Quadriplegia was also detected in cases
      whose exit sites were both upper and lower extremities. Quadriplegia was detected
      in one case whose entry site was hand and the exit site was the contralateral
      hand. Paraplegia was detected in one case in whom the entry site was the hand and
      exit site was the contralateral foot. In our patients, no complete loss of
      sensation was noted. Most of the patients were initially noted to have hypotonia
      between days 2 and 10 after electrical burn and were characterized by ascending
      paralysis, i.e., paraplegia followed by quadriplegia. We can postulate that these
      unique neurological manifestations after electrical injury may be due to the
      anatomical characteristics of the arterial blood supply of the spinal cord. The
      anterior gray matter, especially anterior horn cell is particularly susceptible
      to ischemic injury, because blood is supplied only by the sulcal branch, the
      longest branch originating from the anterior spinal artery. So, under the
      condition that all small sized vessels distributed in the spinal cord undergo
      degenerative change during a similar period of time, any occlusive event caused
      by thrombus or vascular wall injury in the sulcal branch will enhance the risk of
      ischemic injury in its distal area. Furthermore, the spinal cord at T4 to T8
      levels is more vulnerable to ischemic injury due to poor collateral circulations.
      In conclusion, our postulates can explain the diverse patterns of delayed spinal
      cord injury, and enhance the rationale for early administration of prostaglandin
      E1 or steroid treatment to reduce ischemic spinal cord injury in cases of
      electrical burns.

PMID- 15475145
TI  - The impact of skin banking and the use of its cadaveric skin allografts for
      severe burn victims in Singapore.
AB  - The skin banking programme was set-up in Singapore in 1998 to provide a ready
      source of allografts for patients with severe burns. The process and problems in
      establishing a local skin bank will be described together with a retrospective
      review of skin allograft recipients to determine the efficacy of the programme.
      For the skin bank set-up, pertinent issues related to legislation, methods,
      logistics, quality assurance and donation rate are discussed. In this
      retrospective review, a comparison between patients who had early complete
      excision with skin allograft transplantation and those who received conventional
      staged excision and coverage, was analysed in terms of clinical profile and
      outcome using statistical methods. The former group presented a significant
      reduction of mortality rate and hospital stay by 29% and 10 days, respectively.
      The establishment of the skin bank has helped in the management of severe burn
      patients by facilitating early excision and allografting. In a Burn Centre,
      therefore, it is essential to have an ample supply of skin allograft for burn
      victims in readiness for mass disaster situations.

PMID- 15475146
TI  - Scalds in van drivers.
AB  - This report concerns 16 cases of patients admitted to our burns unit, between May
      1997 and June 2003, for burns caused by the explosion of the heating system in
      their vehicles. In 15 of these cases, the vehicle in question was the same; the
      Renault Express van (P < 0.0001 in a Poisson test). While driving their vehicle,
      the patients suffered burns to the lower extremities and the genitals which in
      most cases, required surgery. Three patients suffered accidents after the
      scalding, due to loss of control of their vehicles. This type of injury is
      associated with significant complications.

PMID- 15475147
TI  - The diamond CO2 laser as a method of improving the vascularisation of a permanent
      collagen implant.
AB  - For a biomaterial to be considered as anything other than a simple filler
      material it must allow a certain degree of ingrowth from the surrounding host
      tissues. Permacol is a novel porcine derived biomaterial that is isocynate
      crosslinked to prevent its degradation in vivo, but while it appears to be
      biocompatible in terms of its histological tissue response, our early studies
      demonstrate only a limited degree of fibrovascular ingrowth. The aim of this
      study was to assess the effectiveness of both laser perforations and topically
      applied VEGF as methods of encouraging fibrovascular ingrowth. Treatment of
      Permacol with the diamond CO(2) laser significantly increased the porosity of the
      material as assessed by seescan image analysis. Fibrovascular ingrowth as
      assessed in the Sprague-dawley rat model was found to be limited to the pores
      themselves and not the surrounding native matrix. Pre-soaking of laser treated
      Permacol in vascular endothelial growth factor (VEGF) did not further increase
      fibrovascular ingrowth. Increasing the porosity of Permacol may allow its use as
      a dermal replacement in the support of an overlying skin graft or keratinocyte
      sheet; however using the laser may not be the optimal method of achieving this
      aim.

PMID- 15475148
TI  - Combined use of a collagen-based dermal substitute and a fibrin-based cultured
      epithelium: a step toward a total skin replacement for acute wounds.
AB  - Integra, a dermal replacement, is used as an immediate and temporary coverage for
      acute wounds, after which, autograft is used to reconstitute permanently the
      epidermal coverage. The fibrin sheet-cultured epithelium autograft (FS-CEA) could
      provide an effective alternative to the surgical procedure. To evaluate this
      hypothesis, we compared the association of Integra/FS-CE to Integra/control
      cultured epithelium (control-CE). Their respective abilities: (1) to produce
      dermal-epidermal construct in vitro; (2) to generate skin replacement when
      grafted onto athymic mice were studied. We have shown that: (1) 83% of the FS-CE
      attached to the artificial dermis in vitro compared to only 33% for control-CE;
      (2) retraction of the grafted area was significantly lower 2 weeks after grafted
      with FS-CE than with the control-CE (P < 0.05); (3) 83% of the mice grafted with
      FS-CE showed the presence of a differentiated human epidermis 21 days after
      grafting, while such an epidermis was absent in all the animals of the control-CE
      group. We found that the use of FS-CE greatly improved adhesion, development of
      the epithelium and graft take onto the artificial dermis. We believe this
      technology should significantly improve the performance of dermal-epidermal skin
      replacement for acute wounds.

PMID- 15475149
TI  - Hydrofluoric acid-revisited.

PMID- 15475150
TI  - Paediatric upper limb contracture release following burn injury.
AB  - PURPOSE: The aim of this study was to assess the functional outcome in children
      who had undergone release of upper limb burn contractures at the axilla, elbow
      and wrist. METHODS: We studied a series of 10 patients reconstructed with local
      flaps (n = 5), Integra artificial skin (n = 10) and micro-vascular free tissue
      transfer (n = 5) to release contracted axillae (n = 8), elbows (n = 5) and wrists
      (n = 7). Follow-up ranged from 6 months to 6 years and outcome was assessed by
      functional improvement. RESULTS: Full functional release was achieved in all
      cases at the time of the surgery. Local flaps resulted in good or excellent
      outcomes in all five cases. Six patients reconstructed with Integra were assessed
      as having an excellent outcome whereas four had a poor outcome. Free tissue
      transfer with excellent result was achieved in five children. CONCLUSIONS: This
      series assessed the three treatment options that we have used for the release of
      upper limb post-burn contractures. We have shown that local flaps fashioned from
      burnt skin survive, Integra requires extended post-operative care to prevent
      recontraction and free tissue transfer is safe in young children. Each method
      when used appropriately has produced excellent results which have been maintained
      over the follow-up period.

PMID- 15475151
TI  - Double free flaps harvested from one or two donor sites for one or two-staged
      burn reconstruction: models of sequential-link and independent-link
      microanastomoses.
AB  - Extensive burn injuries and subsequent scarring result in functional and
      aesthetic impairments. The use of free flaps in burn reconstructions provides
      superior outcomes especially when other, more conservative reconstructive methods
      fail and curtail efforts of relentless rehabilitation. Multiple chronic scar
      associated problems and extensive acute burn defects are conventionally resolved
      by multiple procedures. Thus, two or extensive scar regions are typically
      reconstructed using two free flaps (double free flaps) in two separate,
      procedures utilizing two independent donor sites. This leads to a protracted
      course of repetitive operations, hospitalizations, and rehabilitation, causing a
      prolonged period of discomfort and disability. The definition of double free
      flaps is two independent free flaps with two sets of microanastomoses. This paper
      illustrates, via a case-series, that double free flaps could be performed in one
      procedure, with both flaps harvested from either one or two donor sites. Two
      flaps are then utilized to resolve one large or two problem areas at the same
      time. Revascularization of the flaps is achieved via either a sequential-link or
      independent-link microanastomoses. The advantages of harvesting double free flaps
      from one region and using them in one stage to reconstruct one or two defect area
      include: (1) providing a large area of soft, pliable skin from one region for re
      surfacing burn injuries or resolving scar associated problems, (2) decreasing the
      treatment course and potential disability, (3) decreasing donor site morbidities,
      (4) increasing maneuverability and conformability of the flap, and (5) affording
      a better functional and aesthetic outcome.

PMID- 15475152
TI  - Porcine skin: friend or foe?

PMID- 15475153
TI  - Malignant fibrous histiocytoma in a chronic burn scar: a rare case report and
      review of the literature.

PMID- 15475154
TI  - The management of complicated charcoal contact burns involving deep tissues.
AB  - This report describes the management of a charcoal burn involving deep tissues at
      different anatomic sites. The closure of burn wounds should be considered as a
      functional and cosmetic outcome whenever possible. Our aim should be to get the
      soft tissue of the early burned wound closed. A satisfactory result can be
      achieved if both the functional anatomy and the aesthetic outcome can be kept in
      mind while planning the management.

PMID- 15475155
TI  - Amateur branding.

PMID- 15475156
TI  - Porcine xenograft dressing for facial burns: meshed versus non-meshed.

PMID- 15475157
TI  - Women victims of self-inflicted burns.

PMID- 15475158
TI  - Juvenile hormone regulation of the E75 nuclear receptor is conserved in Diptera
      and Lepidoptera.
AB  - Despite longstanding efforts, the juvenile hormone (JH) signaling pathway remains
      unknown. In Drosophila melanogaster (Diptera), JH activates expression of the
      E75A nuclear receptor. The E75 gene encodes a family of related proteins. A
      homologue of Drosophila E75 was previously identified and two isoforms, mE75A and
      mE75B, were reported in Manduca sexta (Lepidoptera). Here, we describe the
      identification of two additional isoforms, mE75C and mE75D, and the hormonal
      regulation of mE75 gene expression in Manduca CH1 cultured cells. mE75A and mE75B
      isoforms are specifically induced by ecdysone in CH1 cells. One isoform, mE75C,
      shows constitutive expression. The mE75D isoform exhibits dual hormonal
      regulation; it can be activated by either ecdysone or the JH analog, methoprene.
      E75-encoded proteins represent the first example of transcription factors
      directly induced by JH. E75 activation by JH, in both Diptera and Lepidoptera,
      suggests a conserved function in the JH signaling pathway.

PMID- 15475159
TI  - Identification and phylogenetic analyses of the protein arginine
      methyltransferase gene family in fish and ascidians.
AB  - Protein arginine methyltransferases (PRMT) involved in the regulations of signal
      transduction, protein subcellular localization, and transcription have been
      mostly studied in mammals and yeast. In this study orthologues of eight human
      PRMT genes (PRMT1-7 and HRMT1L3) were identified in both puffer fish Fugu
      rubripes and zebrafish Danio rerio. The fish PRMT genes appear to be conserved
      with their mammalian orthologues at the levels of amino acid sequences as well as
      genomic structures. All vertebrate PRMT genes contain 10-16 coding exons except
      PRMT6 that contains only one coding exon. Western blot analyses of zebrafish
      tissue extracts confirmed the expression of some PRMT proteins in zebra fish. We
      further identified six PRMT members (PRMT1, 3-7) in an invertebrate chordate
      Ciona intestinalis. Genomic structures of the PRMT orthologues are no more
      conserved in the ascidians, as PRMT3 and PRMT5 contain only one coding exon while
      PRMT6 contains six exons. PRMT2 and HRMT1L3 that are missing in Ciona appear to
      be vertebrate-specific. HRMT1L3 is a PRMT1 paralogue with highly conserved
      sequences and exact exon junctions, whereas the PRMT2 orthologues are very
      diverged. Different PRMT orthologues are likely to evolve at different rates and
      the PRMT1 orthologues appear to be most conserved through evolution. Furthermore,
      phylogenetic analyses using the core regions of various PRMT genes show that
      PRMT5 with the type II PRMT activity is separated in one branch. All other PRMT
      genes including PRMT1, 2, 3, 4, 6, 7 and HRMT1L3 clustered in the other branch,
      probably represent the genes for the type I activity.

PMID- 15475160
TI  - Marsupial relationships and a timeline for marsupial radiation in South Gondwana.
AB  - Recent marsupials include about 280 species divided into 18 families and seven
      orders. Approximately 200 species live in Australia/New Guinea. The remaining
      species inhabit South America with some of these secondarily ranging into North
      America. In this study, we examine marsupial relationships and estimate their
      divergences times using complete mitochondrial (mt) genomes. The sampling, which
      includes nine new mtDNAs and a total number of 19 marsupial genomes, encompasses
      all extant orders and 14 families. The analysis identified a basal split between
      Didelphimorphia and remaining orders about 69 million years before present
      (MYBP), while other ordinal divergences were placed in Tertiary times. The
      monotypic South American order Microbiotheria (Dromiciops gliroides, Monito del
      Monte) was solidly nested among its Australian counterparts. The results suggest
      that marsupials colonized Australia twice from Antarctica/South America and that
      the divergence between Microbiotheria and its Australian relatives coincided with
      the geological separation of Antarctica and Australia. Within Australia itself,
      several of the deepest divergences were estimated to have taken place close to
      the Eocene/Oligocene transition.

PMID- 15475161
TI  - Genomic organization and transcripts of the zebrafish Protocadherin genes.
AB  - We have examined the protocadherin (Pcdh) gene clusters of the zebrafish (Danio
      rerio). At least three sets of the Pcdh gene cluster were found in the zebrafish
      genome. Here, we describe the complete organization of the DrPcdh2 gene clusters.
      Classification by phylogenetic and transcript analyses revealed 7 DrPcdh2omicron,
      20 DrPcdh2alphaa, 12 DrPcdh2alphab, and 1 DrPcdh2alphac variable exons upstream
      of the DrPcdh2alpha constant region exons in the DrPcdh2 gene cluster. The
      constant regions of the DrPcdh1alpha and DrPcdh2alpha genes in zebrafish were
      orthologs of those of the mammalian Pcdhalpha. These exons all encoded plural
      PXXP motifs in their cytoplasmic tails. The sequences of the variable exons were
      highly conserved within each family: DrPcdh2omicron, DrPcdh2alphaa, and
      DrPcdh2alphab. Transcript analysis revealed that zebrafish Pcdhs had
      alternatively spliced variants in the constant region that were not found in
      mammals. More gene clusters, more variable exons, and more alternative splicing
      variants were found in zebrafish than in mammals. Thus, although the Pcdhalpha
      families were common to diverse vertebrates, their gene number, structure, and
      transcripts were different between teleosts and mammals.

PMID- 15475162
TI  - Census of orthologous genes and self-organizing maps of biologically relevant
      transcriptional patterns in chickens (Gallus gallus).
AB  - The launch of large-scale chicken expressed sequence tags (EST) projects has
      placed the chicken in the lead for the number of EST sequences in agriculturally
      important animals. More than 451,000 chicken ESTs derived from over 158 libraries
      have been deposited in the NCBI dbEST database as of December 2003. But how many
      genes these ESTs represent and how they are expressed in different chicken
      tissues/organs remain undetermined. In the present research, we developed a human
      gene-based strategy for census of chicken orthologous genes and identification of
      their expression patterns. Among 34,157 human coding genes used in the study,
      BLAST analysis revealed that 11,066 genes provisionally matched 248,628 chicken
      ESTs. Based on the average EST abundance of the orthologous genes, the current
      public repository of chicken ESTs could represent approximately 20,000
      provisional genes. Analysis of gene expression in 14 single tissues/organs showed
      that approximately 15% of genes were expressed exclusively in single tissue/organ
      whereas the remaining approximately 85% of genes were co-expressed in two or more
      tissues/organs. A majority (91.15%) of genes expressed in chicken embryos were
      also expressed at post-hatch stages, indicating that most genes activated in
      chicken embryos could serve housekeeping functions. Self-organizing maps (SOM)
      analysis organized 8807 provisional genes in selected chicken tissues into 98
      clusters with each cluster being indicative of common regulatory factors and
      pathways. A total of 969 provisional orthologous genes were identified as
      preferentially expressed genes (PEGs) in various chicken tissues/organs
      (LOD>3.0). No doubt, the present study on gene expression patterns will provide
      insight into dynamics of metabolic pathways and tissue/organ programming and
      reprogramming in chickens.

PMID- 15475163
TI  - Lateral gene transfer and the complex distribution of insertions in eukaryotic
      enolase.
AB  - Insertions and deletions in protein-coding genes are relatively rare events
      compared with sequence substitutions because they are more likely to alter the
      tertiary structure of the protein. For this reason, insertions and deletions
      which are clearly homologous are considered to be stable characteristics of the
      proteins where they are found, and their presence and absence has been used
      extensively to infer large-scale evolutionary relationships and events. Recently,
      however, it has been shown that the pattern of highly conserved, clearly
      homologous insertions at positions with no other detectable homoplasy can be
      incongruent with the phylogeny of the genes or organisms in which they are found.
      One case where this has been reported is in the enolase genes of apicomplexan
      parasites and ciliates, which share homologous insertions in a highly conserved
      region of the gene with the apparently distantly related enolases of plants. Here
      we explore the distribution of this character in enolase genes from the third
      major alveolate group, the dinoflagellates, as well as two groups considered to
      be closely related to alveolates, haptophytes and heterokonts. With these data,
      all major groups of the chromalveolates are represented, and the distribution of
      these insertions is shown to be far more complicated than previously believed.
      The incongruence between this pattern, the known evolutionary relationships
      between the organisms, and enolase phylogeny itself cannot be explained by any
      single event or type of event. Instead, the distribution of enolase insertions is
      more likely the product of several forces that may have included lateral gene
      transfer, paralogy, and/or recombination. Of these, lateral gene transfer is the
      easiest to detect and some well-supported cases of eukaryote-to-eukaryote lateral
      transfer are evident from the phylogeny.

PMID- 15475164
TI  - Developmental constraint on gene duplicability in fruit flies and nematodes.
AB  - A previous study in nematodes suggested that developmental constraint reduces the
      duplicability of genes involved in early development. Recent large-scale gene
      expression studies of fly development enabled us to conduct a more detailed study
      of this issue. We found that the average duplicability of genes involved in
      embryonic development is indeed lower than that of genes involved in larval
      development but not significantly lower than that of genes involved in later
      stages of development. Moreover, in both flies and nematodes genes with multiple
      expression peaks do not seem to have a lower duplicability than do genes with a
      single expression peak. Thus, although developmental constraint does appear to
      reduce gene duplicability, the effect seems weak or at best moderate.

PMID- 15475165
TI  - Characterization of the canine desmin (DES) gene and evaluation as a candidate
      gene for dilated cardiomyopathy in the Dobermann.
AB  - Canine-dilated cardiomyopathy (DCM) in dogs is a disease of the myocardium
      associated with dilatation and impaired contraction of the ventricles and is
      suspected to have a genetic cause. A missense mutation in the desmin gene (DES)
      causes DCM in a human family. Human DCM closely resembles the canine disease. In
      the present study, we evaluated whether DES gene mutations are responsible for
      DCM in Dobermann dogs. We have isolated bacterial artificial chromosome clones
      (BACs) containing the canine DES gene and determined the chromosomal location by
      fluorescence in situ hybridization (FISH). Using data deposited in the NCBI trace
      archive and GenBank, the canine DES gene DNA sequence was assembled and seven
      single nucleotide polymorphisms (SNPs) were identified. From the canine DES gene
      BAC clones, a polymorphic microsatellite marker was isolated. The microsatellite
      marker and four informative desmin SNPs were typed in a Dobermann family with
      frequent DCM occurrence, but the disease phenotype did not associate with a
      desmin haplotype. We concluded that mutations in the DES gene do not play a role
      in Dobermann DCM. Availability of the microsatellite marker, SNPs and DNA
      sequence reported in this study enable fast evaluation of the DES gene as a DCM
      candidate gene in other dog breeds with DCM occurrence.

PMID- 15475166
TI  - The characterisation and functional analysis of the human glyoxalase-1 gene using
      methods of bioinformatics.
AB  - Methylglyoxal (MG), which forms MG-derived AGE, is elevated in diabetic subjects
      with vascular disease. Detoxification of MG occurs through the glyoxalase system
      incorporating glyoxalase-1 (GLO1) and glyoxalase-2. Perturbations of the
      glyoxalase-1 gene (GLO1) may result in vulnerability to vascular complications
      through alterations in AGE interactions. We used bioinformatics to predict the
      structure, function and genetic variation of GLO1. We identified a previously
      unreported exon. Seventy single nucleotide polymorphisms (SNPs) were identified
      bioinformatically. The amino acid substitution Ala 111 Glu was confirmed and
      predicted to be tolerant. Though no alternative splice variants were identified,
      novel multiple alternative transcription start sites and alternative 3' UTRs were
      demonstrated. Ubiquitous expression of GLO1 was confirmed. Conserved regulatory
      regions were predicted 5' to the transcription start site and in the distal
      promoter, and several predicted conserved transcription regulatory elements were
      suggested in the 5' UTR. This study of GLO1 demonstrates multiple sequence
      variants at DNA and mRNA levels, areas of sequence conservation and SNPs that are
      predicted to affect function. A differential ability of glyoxalase-1 to reduce
      the formation and subsequent interaction of AGEs may have a role in the
      structural and functional manifestations of diabetic vascular disease.

PMID- 15475167
TI  - Production and secretion of biologically active recombinant canine growth hormone
      by Pichia pastoris.
AB  - Production of recombinant canine (Canis familiaris) growth hormone (rCFGH) by two
      expression systems, methanol utilization slow (Muts) and methanol utilization
      plus (Mut+) based on Pichia pastoris. Led by the Saccharomyces cerevisiae alpha
      mating type signal sequence (SS), the hormone was secreted into the culture
      medium in its mature and active form. The level of total proteins secreted into
      the medium achieved at 25 ml working volume using Erlenmeyer flasks was
      approximately 40 and 15 microg/ml for Muts and Mut+ constructs, respectively. As
      judged by densitometry of proteins resolved by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE), the hormone produced by the
      fermented Mut(s) strain upon induction with methanol reached 24 microg/ml,
      representing around 60% of the total secreted proteins and being eight times more
      abundant than in its Mut+ counterpart. Finally, the recombinant hormone showed
      activity when tested in the Nb2 cell proliferation assay.

PMID- 15475168
TI  - Structure and function of a cellulase gene in redclaw crayfish, Cherax
      quadricarinatus.
AB  - The most abundant organic compound produced by plants is cellulose; however, it
      has long been accepted that most animals do not produce endogenous enzymes
      required for its degradation, but rely instead on symbiotic relationships with
      microbes that produce the necessary enzymes. Here, we present the genomic
      organisation of an endogenous glycosyl hydrolase family (GHF) 9 gene in redclaw
      crayfish (Cherax quadricarinatus), consolidated from a cDNA sequence determined
      by Byrne et al. [Gene 239 (1999) 317-324.]. Comparison with several other
      invertebrate GHF9 genes reveals the conservation of both intron position/phase
      and splice sequence, which adds support to an argument for an ancestral animal
      cellulase gene. Furthermore, two introns in plant GHF9 genes are also identical
      in position, implying a more ancient origin for this class of animal cellulase.
      Protein purification from redclaw gastric fluid via fast performance liquid
      chromatography (FPLC) indicated the presence of two endoglucanase enzymes. The
      molecular weights of these components were determined by matrix-assisted laser
      desorption/ionisation-time-of-flight (MALDI-TOF) to be 47,887 Da (Cel1) and
      50,295 Da (Cel2). Cel1 is possibly the functional product of the described
      cellulase gene, with N-terminal amino acid residues identical to the translated
      amino acid sequence from the corresponding gene region. Cel2 was identical to
      Cel1 for 7 of 11 N-terminal residues and likely to be the product of a paralogous
      endoglucanase gene. These results suggest that redclaw crayfish possess at least
      one and possibly two functional, endoglucanase enzymes, although further work is
      required to confirm their origin and attributes.

PMID- 15475169
TI  - Estrogen receptor-related receptor gamma has an exceptionally broad specificity
      of DNA sequence recognition.
AB  - Estrogen receptor-related receptors (ERRs) constitute a subfamily of the nuclear
      hormone receptor superfamily. ERRs are closely related to estrogen receptors
      (ERs), but apparently lack ligand dependence. In this study, we cloned rat
      ERRgamma as an interacting partner of an orphan nuclear receptor, small
      heterodimer partner (SHP). ERRgamma exhibited significant binding affinities with
      a wide spectrum of sequences: inverted and direct repeat motifs composed of
      AGGTCA half-sites with various spacings, as well as a monovalent motif of the
      same sequence carrying extra T(C/G)A trinucleotides on the 5' side. On the other
      hand, inverted repeat spaced by three nucleotides was dominantly efficient for
      the binding of ERalpha. These results were mostly consistent with those of gene
      reporter assays. ERRgamma bound as a homodimer to all binding sequences tested,
      including a monovalent binding site, and ERRgamma did not heterodimerize with
      ERalpha. Taken together, ERRgamma recognizes a tremendously broad range of
      sequences as a homodimer. Finally, we found that SHP efficiently represses the
      transcriptional activity of ERRgamma, even at a far lower concentration than that
      of ERRgamma.

PMID- 15475170
TI  - A novel Giraffidae-specific interspersed repeat with a microsatellite, originally
      found in an intron of a ruminant paralogous p97bcnt gene.
AB  - The ruminant-specific p97bcnt gene (bcntp97) is a paralogous gene that includes a
      region derived from a retrotransposable element 1 (RTE-1). The region comprises
      an exon (RTE-1 exon) encoding 325 amino acids in the middle of the p97bcnt
      protein. To understand how the bcntp97 paralog evolved, we examined its
      organization in several ruminants. We found a 700-base pair (bp) insert in the 5'
      intron of the RTE-1 exon in giraffe bcntp97. This insert is missing in the
      corresponding regions of bovine and sika deer. Furthermore, the sequence of the
      insert is interspersed in the genome of giraffe but not bovine and also contains
      a (GA)n microsatellite. A highly homologous insert harboring significantly
      different (GA)n microsatellite was detected in the corresponding region of okapi
      bcntp97. Therefore, the interspersed fragments with (GA)n microsatellite might
      serve as a marker for tracking how duplicated genes evolve in a family-specific
      manner.

PMID- 15475171
TI  - Comparative analysis of Brachyury T-domains, with the characterization of two new
      sponge sequences, from a hexactinellid and a calcisponge.
AB  - The Brachyury family of T-domain containing transcription factor has been
      recently the subject of a number of Evo-Devo studies, with expression data
      obtained from a wide sampling of eumetazans, pointing to a possible conserved
      role in the formation of the blastopore and the extremities of the digestive
      tract. Here we present a comparative analysis of Brachyury sequences at the
      metazoan scale, using published data and two new sponge Brachyury sequences.
      Alignment features, gene phylogeny, and the evolution of variable positions
      within the T-domain are discussed in the light of available data about functional
      constraints on the residues. Interestingly, the high sequence divergence observed
      in Brachyury T-domains from sponges appears to be mostly the consequence of
      autapomorphic changes within the sponge lineages, rather than the retention of
      primitive character states.

PMID- 15475172
TI  - Rapid turnover and species-specificity of vomeronasal pheromone receptor genes in
      mice and rats.
AB  - Pheromones are used by individuals of the same species to elicit behavioral or
      physiological changes, and they are perceived primarily by the vomeronasal organ
      (VNO) in terrestrial vertebrates. VNO pheromone receptors are encoded by the V1r
      and V2r gene superfamilies in mammals. A comparison of the V1r and V2r
      repertoires between closely related species can provide significant insights into
      the evolutionary genetic mechanisms responsible for species-specific pheromone
      communications. A total of 137 putatively functional V1r genes of 12 families
      were previously identified from the mouse genome. We report the identification of
      95 putatively functional V1r genes from the draft rat genome sequence. These
      genes map primarily to four blocks in two chromosomes. The rat V1r genes can be
      phylogenetically grouped into 10 families, which are shared with mouse, and 2 new
      families, which are rat-specific. Even in many shared families, gene numbers
      differ between the two species, apparently due to frequent gene duplication and
      pseudogenization after the separation of the two species. Molecular dating
      suggests that most of the rat V1r families emerged before or during the radiation
      of mammalian orders, but many duplications within families occurred as recently
      as in the past 10 million years (MY). Our results show that the evolution of the
      V1r repertoire is characterized by exceptionally fast gene turnover via gains and
      losses of individual genes, suggesting rapid and substantial changes in pheromone
      communication between species.

PMID- 15475173
TI  - Impaired recovery from naphthalene-induced bronchiolar epithelial injury in mice
      exposed to aged and diluted sidestream cigarette smoke.
AB  - The effect of sidestream tobacco smoke combined with other pollutants is largely
      unknown. Previously, we found that distal airway epithelial repair was inhibited
      in mice exposed to sidestream tobacco smoke (TS) for 5 days followed by single
      exposure to naphthalene (NA), a common polycyclic aromatic hydrocarbon found in
      cigarette smoke, diesel exhaust, and pesticide formulations. The main injury
      target of NA is the nonciliated (Clara) bronchiolar cell. NA injury normally
      resolves in two weeks. Repair in mice exposed to TS and NA was unresolved in the
      distal bronchioles 14 days post-NA injury. We hypothesized that repair inhibition
      persisted as a first step towards long-term airway remodeling and expanded the
      previous study by evaluating repair 21 days after acute NA injury. Repair was
      evaluated using high resolution histopathology, TEM, and quantitative
      morphometry. In animals exposed to TS and NA, repair was still impaired; re
      differentiation of Clara cells at the bronchoalveolar duct junction was
      incomplete, indicating repair was continuing. Compared to 14 days post-NA-injury,
      repair at 21 days post-NA treatment was more extensive. Animals exposed only to
      TS had epithelium similar to controls. While TS exposure impairs bronchiolar
      epithelial repair after NA exposure, this effect appears to be slowly resolving
      over time.

PMID- 15475174
TI  - Differential in vitro neurotoxicity of the flame retardant PBDE-99 and of the PCB
      Aroclor 1254 in human astrocytoma cells.
AB  - Polybrominated diphenyl ethers (PBDEs) are an important class of flame
      retardants. Because of their presence in maternal milk and their structural
      similarity to polychlorinated biphenyls (PCBs), concern has been raised on their
      possible developmental neurotoxicity. Aim of the present study was to investigate
      the in vitro effects of PBDE-99 (2,2', 4,4', 5-pentabromodiphenyl ether) on
      astroglial cells (human 132-1N1 astrocytoma cells) and comparing it with those of
      the PCB mixture Aroclor 1254. Both PBDE-99 and Aroclor 1254 caused a
      concentration-dependent inhibition of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide) reduction, however, only the latter increased
      lactate dehydrogenase (LDH) release or cell death, assessed by the trypan blue
      assay. PBDE-99 caused translocation of the three protein kinase C (PKC) isozymes
      (alpha, epsilon, zeta) present in 132-1N1 astrocytoma cells, while Aroclor 1254
      affected only PKCalpha and epsilon translocation. However, pre-incubation with
      the PKC inhibitor GF109203X or PKC down-regulation by the phorbol ester PMA, had
      minimal or no effect on PBDE-99 or Aroclor 1254-induced cytotoxicity. Similarly,
      the calcium chelator BAPTA-AM, the tyrosine kinase inhibitor genistein, and the
      MEK (mitogen activated protein kinase kinase) inhibitor PD98059 had no effect on
      PBDE-99 and Aroclor 1254 cytoxicity. On the other hand, the phosphatidylinositol
      3 kinase (PI-3K) inhibitor LY290042 enhanced PBDE-99 toxicity, but did not affect
      Aroclor 1254. Because of the involvement of PI-3K in apoptotic cell death, the
      ability of PBDE-99 and Aroclor 1254 to induce apoptosis in astrocytoma cells was
      investigated. PBDE-99, but not Aroclor 1254, caused apoptotic cell death in
      astrocytoma cells, assessed by the TUNEL method and by Hoechst 33258 staining,
      via a p53 dependent mechanism. These results suggest that PBDE-99 and Aroclor
      1254 exert differential cytotoxic effects on human astroglial cells.

PMID- 15475175
TI  - Evaluation of the apoptogenic potential of hard metal dust (WC-Co), tungsten
      carbide and metallic cobalt.
AB  - The present study aimed at comparing in vitro the apoptogenic properties of
      metallic cobalt (Co), tungsten carbide (WC) and tungsten carbide-cobalt (WC-Co)
      in conditions known to cause genotoxicity. Human peripheral blood mononucleated
      cells were incubated with 2.0-6.0 microg/ml of Co alone or mixed with WC
      particles and 33.3-100.0 microg/ml WC alone for up to 24 h. Under these culture
      conditions the majority (60%) of the cobalt metal particles were almost
      immediately solubilised in the culture medium, while WC remained under the form
      of particles that were progressively phagocytosed by monocytes. Apoptosis was
      assessed by Annexin-V staining, flow cytometry and analysis of DNA fragmentation
      by ELISA. Metallic Co-particles induced apoptosis in vitro. Furthermore, although
      so far considered as biologically inert, WC particles also induced apoptosis.
      When compared with its individual components WC-Co displayed an additive
      apoptotic effect in the DNA fragmentation assay. Apoptosis induced by WC
      particles was found largely dependent on caspase-9 activation and occurred
      presumably in monocytes, while that induced by Co involved both caspase-9 and -8
      activation. The data suggest that apoptosis induced by the tested WC-Co mixture
      results from the additive effects of WC apoptosis induced in monocytes and Co
      specific apoptosis in both monocytes and lymphocytes. The apoptogenic properties
      of these metals may be important in the mechanism of lung pathologies induced by
      the cobalt-containing particles.

PMID- 15475176
TI  - Lead nitrate-induced development of hypercholesterolemia in rats: sterol
      independent gene regulation of hepatic enzymes responsible for cholesterol
      homeostasis.
AB  - Changes in the gene expressions of hepatic enzymes responsible for cholesterol
      homeostasis were examined during the process of lead nitrate (LN)-induced
      development of hypercholesterolemia in male rats. Total cholesterol levels in the
      liver and serum were significantly increased at 3-72 h and 12-72 h, respectively,
      after LN-treatment (100 micromol/kg, i.v.). Despite the development of
      hypercholesterolemia, the genes for hepatic 3-hydroxy-3-methylglutaryl-CoA
      reductase (HMGR) and other enzymes (FPPS, farnesyl diphosphate synthase; SQS,
      squalene synthase; CYP51, lanosterol 14alpha-demethylase) responsible for
      cholesterol biosynthesis were activated at 3-24 h and 12-18 h, respectively. On
      the other hand, the gene expression of cholesterol 7alpha-hydroxylase (CYP7A1), a
      catabolic enzyme of cholesterol, was remarkably suppressed at 3-72 h. The gene
      expression levels of cytokines interleukin-1beta (IL-1beta) and TNF-alpha, which
      activate the HMGR gene and suppress the CYP7A1 gene, were significantly increased
      at 1-3 h and 3-24 h, respectively. Furthermore, gene activation of SREBP-2, a
      gene activator of several cholesterogenic enzymes, occurred before the gene
      activations of FPPS, SQS and CYP51. This is the first report demonstrating sterol
      independent gene regulation of hepatic enzymes responsible for cholesterol
      homeostasis in LN-treated male rats. The mechanisms for the altered-gene
      expressions of hepatic enzymes in LN-treated rats are discussed.

PMID- 15475177
TI  - Expression profiles of zinc transporters in rodent placental models.
AB  - Zinc is a vital metal that is a structural and functional component of many
      proteins. The precise mechanism of zinc transport in the placenta remains
      unclear. In this study, we investigated the expression of zinc transporters
      (ZnTs) in the mouse placenta and in two rat trophoblast cell lines, TR-TBT cells,
      which are syncytiotrophoblast cells of the labyrinth zone, and Rcho-1 cells,
      which retain trophoblast cell features and differentiate into trophoblast giant
      cells of the junctional zone. All of the ZnTs that have been identified in mice
      (ZnT1-7) were detected in the mouse placenta by RT-PCR. The expression profiles
      of ZnTs in the placenta during pregnancy were different. The mRNA levels of ZnTs,
      with the exception of ZnT7, did not change during pregnancy. The ZnT7 mRNA level
      in placenta was elevated during pregnancy. In TR-TBT cells, ZnT1, ZnT3 and ZnT4
      were detected by RT-PCR analysis. In Rcho-1 cells, all of the ZnTs that have been
      identified in rats (ZnT1-4) were detected by RT-PCR analysis. There were no
      differences between the mRNA expression levels of ZnT family members in
      undifferentiated Rcho-1 cells and differentiated Rcho-1 cells. This is the first
      report of expression profiles of ZnTs during differentiation of the placenta in
      the mouse placenta and rat placental cell models.

PMID- 15475178
TI  - Ethosuximide and valproate display high efficacy against lindane-induced seizures
      in mice.
AB  - Both lindane (gamma-hexachlorocyclohexane), an organochlorine ectoparasiticide
      and pentylenetetrazol, used as a model of experimental epilepsy, produce
      convulsive seizures resulting from the blockade of the gamma-aminobutyric acid
      (GABAA) receptor. In the present study we established the protective effects of
      ethosuximide and valproate against seizures induced by lindane and compared them
      with the well-known protective effects of these drugs against pentylenetetrazol
      induced seizures in mice. Both ethosuximide and valproate afforded complete and
      dose-dependent protection against seizures induced by lindane. However, the
      potencies of these drugs were lower than those obtained against pentylenetetrazol
      seizures. Nevertheless, the protective efficacy of ethosuximide and valproate
      against experimentally induced lindane seizures may suggest possible efficacy of
      these drugs against seizures in lindane-poisoned patients.

PMID- 15475179
TI  - Atrazine is a competitive inhibitor of phosphodiesterase but does not affect the
      estrogen receptor.
AB  - Atrazine (ATR), 2-chloro-4-ethylamino-6-isopropylamino-s-triazine, has been
      implicated in numerous studies to act as an endocrine disruptor, specifically by
      altering estradiol signaling via increased aromatase activity. Fluorescence
      polarization (FP) was used to show that the binding equilibria between estrogen
      receptor-alpha or estrogen receptor-beta, and estradiol were not affected by ATR
      and its metabolites: ATR-desethyl (ADE), ATR-desisopropyl (ADI), ATR
      desethyldesisopropyl (ADD) and terbuthylazine (TBZ). Therefore, ATR and its
      degradation products were studied to determine their ability to inhibit
      phosphodiesterase (PDE), the enzyme responsible for hydrolyzing the second
      messenger cAMP to 5'-AMP. Using FP, it was found that ATR inhibited PDE with an
      IC50 value of 1.8 microM. This was lower than the known PDE inhibitor isobutyl
      methylxanthine (IBMX), which had an IC50 value of 4.6 microM. The ATR degradation
      products ADE, ADI, ADD and TBZ were less effective than ATR at inhibiting PDE
      when assayed using FP. Classical competitive binding assays, using radiolabeled
      14C-cAMP in conjunction with thin layer chromatography (TLC), were used to
      determine that ATR was a competitive inhibitor of PDE with an association
      constant of 85 microM.

PMID- 15475180
TI  - Anti-arthritic effect and subacute toxicological evaluation of Baccharis
      genistelloides aqueous extract.
AB  - This work studies the potential subacute toxicological effects of the aqueous
      extract of Baccharis genistelloides (AEBg) and demonstrates a new anti-arthritic
      therapeutic effect. The treatment of the collagen-induced arthritis (CIA) group
      with 4.2 mg/kg AEBg induced an important decrease (75%) in CIA severity in all
      animals, while the 42 mg/kg dose treated only 50% of animals. After AEBg
      treatment, no significant differences were observed in body weight, aspect, color
      and relative weight of liver, kidneys, thymus or lungs between CIA groups. CIA
      and healthy AEBg groups treated with both doses did not show genotoxic effects to
      liver and kidney cells by the Comet assay, compared to its own control group. The
      augmented AST in the CIA group, compared to healthy control one was regularized
      by the AEBg treatment with 4.2 mg/kg but not with 42 mg/kg. No other significant
      difference was found on serum biochemical parameters, as well as on spontaneous
      or stimulated lymphocyte proliferation between CIA groups. The treatment of
      healthy animals with AEBg 4.2 mg/kg did not change the aspect, color or relative
      weight of kidneys, liver or lungs but reduced the body weight, the thymus and
      popliteal lymph node (PLN) relative weight and serum glucose and triglyceride
      levels. Concluding, our results indicate an anti-arthritic effects of AEBg
      without liver and kidney subacute toxicity and hypoglycemic and
      hypotriglyceridemic actions on healthy animals.

PMID- 15475181
TI  - The role of glutathione transferases in cadmium stress.
AB  - Using Saccharomyces cerevisiae as experimental model, we observed that cells
      mutated in the GTT1 or GTT2 genes showed twice as much cadmium absorption than
      the control strain. We proposed that the formation of the cadmium-glutathione
      complex is dependent on that transferase, since it was previously demonstrated
      that the cytoplasmic levels of this complex affect cadmium uptake. The addition
      of glutathione monoethyl ester (GME), a drug that mimics glutathione (GSH), to
      gtt1Delta cells restored the levels of metal absorption to those of the control
      strain. However, with respect to gtt2Delta cells, addition of GME did not alter
      the capacity of removing cadmium from the medium. Taken together, these results
      suggest that Gtt1 and Gtt2 play different roles in the mechanism of cadmium
      detoxification. By analyzing the toxic effect of this metal, we verified that
      gtt2Delta and gsh1Delta cells showed, respectively, higher and lower tolerance to
      cadmium stress than control cells, suggesting that although GSH plays a relevant
      role in cell protection, formation of the GSH-Cd conjugate is deleterious to the
      mechanism of defense.

PMID- 15475182
TI  - Assessment of cadmium impregnation in women suffering from endometriosis: a
      preliminary study.
AB  - Environmental chemicals with oestrogen-like activity are suspected aetiological
      factors of endometriosis. In animal experiments, cadmium was recently shown to
      possess oestrogen-like properties. In the frame of a case-control study designed
      to investigate environmental risk factors for endometriosis, we compared cadmium
      urinary excretion (CdU) and blood concentration in 59 patients with peritoneal
      endometriosis, deep endometriotic (adenomyotic) nodules of the recto-vaginal
      septum and controls. After standardisation for age (30 years) and smoking status,
      the mean levels of cadmium in urine were (geometric mean [geometric S.D.]) 0.25
      [1.50], 0.29 [1.76] and 0.26 [1.46] microg/g creatinine, respectively. Cadmium
      concentrations in blood did not differ among the three groups. These data,
      therefore, do not support a role for cadmium in the onset or the growth of
      endometriosis or deep endometriotic (adenomyotic) nodules of the recto-vaginal
      septum.

PMID- 15475183
TI  - Subchronic acrylamide treatment induces a tissue-specific increase in DNA
      synthesis in the rat.
AB  - Chronic treatment with acrylamide results in increased incidence of adrenal
      (pheochromocytoma), testicular (mesotheliomas) and thyroid (adenoma) neoplasia in
      male rats. While acrylamide has been demonstrated to be DNA reactive, the tissue
      pattern of neoplasm induction by acrylamide suggests other mechanisms in addition
      to DNA reactivity may be involved in the carcinogenesis of this compound. The
      present studies were performed to determine whether acrylamide or an acrylamide
      metabolite altered cell growth in the neoplastic target tissues in the rat. DNA
      synthesis, mitosis and apoptosis were examined in F344 and Sprague-Dawley male
      rats treated with acrylamide (0, 2, or 15 mg/kg/day) for 7, 14, or 28 days.
      Acrylamide increased DNA synthesis in the target tissues for tumor development
      (thyroid, testicular mesothelium, adrenal medulla) in both rat species. In
      contrast, cell growth was not altered in the liver and adrenal cortex (non-target
      tissues for acrylamide carcinogenesis). No changes in apoptosis or mitosis were
      observed in any of the tissues examined. Inhibition of oxidative metabolism of
      acrylamide using 1-aminobenzotriazole reduced acrylamide-induced DNA synthesis
      only in the adrenal medulla, having no apparent effect in the testicular
      mesolthelium or thyroid. In summary, acrylamide produced a selective increase in
      DNA synthesis that correlates with the previously reported tumor target tissues.

PMID- 15475184
TI  - Inflammatory and genotoxic responses during 30-day welding-fume exposure period.
AB  - Welder's pneumoconiosis has generally been determined to be benign and
      unassociated with respiratory symptoms based on the absence of pulmonary-function
      abnormalities in welders with marked radiographic abnormalities. In previous
      studies, the current authors suggested a three-phase lung fibrosis process to
      study the pathological process of lung fibrosis and found that the critical point
      for recovery was after 30 days of welding-fume exposure at a high dose, at which
      point early and delicate fibrosis was observed in the perivascular and
      peribronchiolar regions. Accordingly, the current study investigated the
      inflammatory and genotoxic responses during a 30-day period of welding-fume
      exposure to elucidate the process of fibrosis. As such, rats were exposed to
      manual metal arc-stainless steel (MMA-SS) welding fumes at concentrations of 65.6
      +/- 2.9 (low dose) and 116.8 +/- 3.9 mg/m3 (high dose) total suspended
      particulate for 2 h per day in an inhalation chamber for 30 days. Animals were
      sacrificed after the initial 2 h exposure, and after 15 and 30 days of exposure.
      The rats exposed to the welding fumes exhibited a statistically significant (P <
      0.05) decrease in body weight when compared to the control during the 30-day
      exposure period, yet an elevated cellular differential count and higher levels of
      albumin, LDH, and beta-NAG, but not elevated TNF-alpha, and IL-1beta in the
      acellular bronchoalveolar lavage fluid. In addition, the DNA damage resulting
      from 30 days of welding-fume exposure was confirmed by a comet assay and the
      inmmunohistochemistry for 8-hydroxydeoxyguanine (8-OH-dG). Consequently, the
      elevated inflammatory and genotoxic indicators confirmed the lung injury and
      inflammation caused by the MMA-SS welding-fume exposure.

PMID- 15475185
TI  - The roles of dopamine transporter and Bcl-2 protein in the protection of CV1-P
      cells from 6-OHDA-induced toxicity.
AB  - 6-Hydroxydopamine (6-OHDA) is widely used to produce an animal model of
      Parkinson's disease by selectively destroying the catecholaminergic nerve system
      of the substantia nigra. In our previous studies we noted that dopaminergic
      neuroblastoma cells (SH-SY5Y) die mostly via apoptosis after exposure to 6-OHDA
      (< or = 100 microM) but African green monkey fibroblast (CV1-P) cells do not
      succumb, although in both cell lines there were increased intracellular p53
      levels. This study was designed to further investigate the mechanisms underlying
      the p53 elevation. To test how 6-OHDA penetrates into fibroblast cells and
      affects p53 levels, we investigated the presence of the dopamine transporter
      (DAT) in CV1-P cells. We showed by western hybridization that CV1-P cells contain
      the DAT. The apparent entry of 6-OHDA into fibroblasts was decreased by the DAT
      inhibitor, 1-(2-bis-(4-fluorophenyl)methoxy)ethyl)-4-(3-phenyl-propyl)piperazine
      (GBR 12909). Pre-treatment with GBR 12909 decreased the elevation of
      intracellular ROS to the control level and thus prevented the increase of p53
      levels in 6-OHDA-treated CV1-P cells. Moreover, an increase of Bcl-2, an
      antiapoptotic protein, was detected after 6-OHDA treatment, supporting our
      previous results where no increase in caspase-3 activity was detected. We suggest
      that Bcl-2 may block the activation of the caspase cascade and protect CV1-P
      cells from apoptosis.

PMID- 15475186
TI  - Blood-forming system in rats after whole-body microwave exposure; reference to
      the lymphocytes.
AB  - The influence of 2.45 GHz microwave (RF/MW) irradiation on blood-forming cells
      after whole-body irradiation of rats was investigated. The exposures were
      conducted with a field power density of 5-10 mW/cm2, and whole-body average
      specific absorption rate (SAR) of 1-2 W/kg. Four experimental subgroups were
      created and irradiated 2, 8, 15 or 30 days, for 2 h a day, 7 days a week.
      Concurrent sham-exposed rats were also included in the study. The cell response
      was assessed by number and type of the bone marrow nuclear cells and peripheral
      blood white cells using standard laboratory methods. Significant decrease in
      lymphoblast count was obtained at 15 and 30th experimental day (P < 0.05),
      whereas other examined parameters did not significantly differed in comparison to
      the sham-exposed controls. The findings point out at stress response in blood
      forming system in rats after selected microwave exposure, which could be
      considered rather as sign of adaptation than malfunction.

PMID- 15475187
TI  - Participation of BER and NER pathways in the repair of DNA lesions induced at low
      N-nitrosodiethylamine concentrations.
AB  - In the present work, we evaluated (p < 0.05) the participation of base excision
      repair (BER) and nucleotide excision repair (NER) mechanisms in repairing DNA
      lesions induced by N-nitrosodiethylamine (NDEA) at 1.5 ng/mL-36.5 microg/mL,
      through cell survival, in different single and double Escherichia coli DNA repair
      mutants (uvrA, uvrB, uvrC, fpg, nth, xthA, fpg/nth, uvrA/fpg, fpg/xthA, mutY, and
      fpg/mutY), using pre-incubation periods of 90 min. Mutant strains BH20 (fpg) and
      AB1886 (uvrA) showed microsomal enzyme (S9 mix) independent NDEA cytotoxicity.
      Cytotoxicity was also detected at lowest NDEA concentrations, in the presence of
      S9 mix, with strains BH980 (mutY) and BH990 (fpg/mutY). NDEA cytotoxicity,
      without S9 mix, was detected for mutant strains AB1884 (uvrC) and AB1885 (uvrB).
      Through SOS chromotest with 90 min of pre-incubation for uvrA and nth strains,
      only NER was shown to be required for repairing NDEA-induced lesions with or
      without metabolic activation. PQ37 and PQ66 strains, both uvrA mutants, showed
      different levels of NDEA sensitivity. The findings suggest that, under the used
      conditions, and at low concentrations, NDEA-induced lesions require both repair
      pathways.

PMID- 15475188
TI  - Cremophor EL augments the cytotoxicity of hydrogen peroxide in lymphocytes
      dissociated from rat thymus glands.
AB  - The pharmaceutical uses of cremophor EL, a non-ionic surfactant, are similar to
      those of polysorbate 80. In our previous study, polysorbate 80 exerted some
      adverse actions on rat thymocytes under in vitro condition. Therefore, the
      effects of cremophor EL on thymic lymphocytes were examined using a flow
      cytometer with appropriate fluorescent dyes. Cremophor EL at 10 microg/ml or more
      (up to 300 microg/ml) concentration-dependently decreased cellular content of
      glutathione. The cell viability of thymocytes under control condition was 95.4 +/
      1.2% (n = 7, mean +/- S.D.). The incubation of thymocytes with 300 microg/ml
      cremophor EL or 3 mM hydrogen peroxide for 2 h, respectively, decreased the cell
      viability to 90.8 +/- 2.8% or 91.2 +/- 2.6%. However, the simultaneous incubation
      with cremophor EL and hydrogen peroxide decreased the cell viability to 28.7 +/-
      8.2%. Cremophor EL at 100 microg/ml accelerated the process of cell death induced
      by hydrogen peroxide. Results suggest that cremophor EL increases the
      susceptibility to oxidative stress. Cremophor EL at clinically relevant
      concentrations may increase the therapeutic potential of some anticancer agents
      to produce oxidative stress.

PMID- 15475189
TI  - Urinary arsenic speciation and porphyrins in C57Bl/6J mice chronically exposed to
      low doses of sodium arsenate.
AB  - Arsenic has been classified as a human carcinogen based on epidemiological data
      however the mechanism of its carcinogenicity is still unclear. Urinary biomarkers
      for chronic arsenic exposure would be valuable as an early warning indicator for
      timely interventions. In this study, young female C57Bl/6J mice were given
      drinking water containing 0, 100, 250 and 500 microg Asv/L as sodium arsenate ad
      libitum for 12 months. Urine was collected bimonthly for urinary arsenic
      methylation assay and porphyrin analysis. All detectable arsenic species showed
      strong linear correlation with administered dosage and the arsenic methylation
      patterns were similar in all three treatment groups. No significant changes of
      methylation patterns were observed over time for either the control or test
      groups. Urinary coproporphyrin III was significantly increased in the 8th month
      in 250 and 500 microg/L groups and remained significantly dose-related after 10
      and 12 months. Coproporphyrin I also showed a significant dose-response
      relationship after 12 months. Our results confirm that urinary arsenic is a
      useful biomarker for internal dose. The alteration of porphyrin profile suggests
      that arsenic can affect the heme metabolism and this may occur prior to the onset
      of arsenic induced carcinogenesis.

PMID- 15475190
TI  - Modification of benzo(a)pyrene-(BaP)-induced forestomach carcinogenesis in mice
      by means od extract of the bark of Astonia scholaris (ASE).

PMID- 15475192
TI  - Bone resorption activity of osteolytic metastatic lung and breast cancers.
AB  - Production of bone resorption mediators and bone resorption activity were
      compared among osteolytic metastatic cancers, normal bone tissues, and soft
      tissue metastatic cancers to search for the possible factors leading to cancer
      induced bone resorption. Twenty-five patients with untreated osteolytic
      metastatic breast or non-small cell lung cancers consisted of the study group.
      Normal bone tissues obtained from the same patient were used as internal
      controls; and tumor tissues from patients with soft tissue metastasis were used
      as external controls. Serum and urinary bone turnover markers were measured.
      Tissues harvested during surgery were subjected to tissue culture. The levels of
      prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha), and interleukin
      6 (IL-6) in the supernatant after 72 h of culture were measured. Bone resorption
      activity was measured by calcium release from cultured calvarias, and bone volume
      as well as osteoclast number in bone sections. Patients with osteolytic
      metastatic cancers showed significantly decreased serum osteocalcin, increased
      serum alkaline phosphatase, and urinary deoxypyridinoline levels. Osteolytic
      metastatic cancers produced significantly more PGE2 than both controls.
      Conditioned medium from osteolytic metastatic tumors showed significantly
      enhanced bone resorption activity, and indomethacin significantly reduced this
      activity. Levels of PGE2, and bone resorption activity increased in osteolytic
      tumor tissues than soft tissue metastatic tissues in the same patient indicated
      that the same tumor cells might respond differently to different
      microenvironments. Our observation showed that PGE2 was produced by osteolytic
      metastatic cancers and stimulated bone resorption in mice calvarias. PGE2
      inhibitor may be applicable in reducing bone resorption by osteolytic metastatic
      cancers.

PMID- 15475193
TI  - Effect of ketoprofen in topical formulation on vascular endothelial growth factor
      expression and tumor growth in nude mice with osteosarcoma.
AB  - OST cells, a low metastatic cell line established from human osteosarcoma, were
      inoculated under the periosteum of the ossa cranii of nude mice. Four weeks
      later, tumors were percutaneously treated for an additional 4 weeks with a patch
      containing either placebo or ketoprofen (KP). In the placebo group, OST cells
      formed osteoid and invaded the cranial bone. Tumor mass weighed 3.54 g.
      Approximately 85% of cells within the tumor expressed proliferating cell nuclear
      antigen (PCNA), indicating that they were proliferating with a high mitotic
      activity. Many feeder vessels were located within the tumor. The majority of
      tumor cells expressed intensely vascular endothelial growth factor (VEGF). In the
      KP group, invasion of OST cells into the cranial bone was suppressed and the
      tumor mass was 47% of that of the placebo group. Approximately 65% of cells
      within the tumor were PCNA-negative, indicating that their growth was arrested.
      There were considerably fewer feeder vessels within the tumor in the KP group
      than in the placebo group. Only a small number of cells expressed VEGF. Based on
      these findings, we concluded that topical administration of KP to nude mice with
      osteosarcoma inhibited VEGF expression, reduced the development of feeder vessels
      for supply of nutrients and oxygen, and suppressed tumor growth.

PMID- 15475194
TI  - Hypoxia induces HIF-1alpha and VEGF expression in chondrosarcoma cells and
      chondrocytes.
AB  - Like other tumors, chondrosarcoma must induce neovascularity as they grow. Recent
      studies have demonstrated that chondrosarcoma are vascular. Since normal
      cartilage is a hypoxic, yet avascular tissue and since chondrosarcoma bears some
      phenotypic relation to cartilage, it is not clear if hypoxic pathways remain
      intact in these tissues. Hypoxia-inducible factor 1alpha (HIF-1alpha) is the
      inducible subunit of the HIF-1 transcription factor that regulates genes involved
      in the response to hypoxia, some of which promote neovascularity. Vascular
      endothelial growth factor (VEGF) is one of the genes upregulated by HIF-1 and is
      the primary cytokine related to angiogenesis. In this study we examined the
      response of chondrocytes and chondrosarcoma cell lines to hypoxia. We found that
      both normal and malignant chondrocytes increased HIF-1alpha protein expression in
      an oxygen concentration dependent manner and also increased VEGF mRNA expression
      in response to hypoxia. HIF-1alpha protein and VEGF mRNA decreased when
      chondrosarcoma cells were transfected with siRNA targeting HIF-1alpha prior to
      hypoxia exposure, suggesting that HIF-1alpha expression resulted in increased
      VEGF expression. The role of the HIF-1alpha/VEGF pathway in angiogenesis in
      chondrosarcoma in vivo and its usefulness as a target for antiangiogenic
      treatment strategies for this tumor requires further investigation.

PMID- 15475195
TI  - Zonal and topographical differences in articular cartilage gene expression.
AB  - Articular cartilage is composed of phenotypically different zones. In young
      articular cartilage, there are only two distinct zones: superficial and growth.
      The zones have different mechanical properties and play specific roles within
      functional cartilage tissue. In small animal models, it is difficult to separate
      the zones quickly and efficiently using only a dissecting microscope. Surface
      abrasion is a method that has been developed to harvest cells from articular
      cartilage to produce highly purified samples in a simple, reproducible process.
      Using this harvesting technique, the superficial zone has been separated from the
      underlying growth zone. Superficial cells comprised approximately 4% of the total
      cells obtained. Superficial and growth zone chondrocytes from articular cartilage
      were analyzed using real-time RT-PCR. Expressed superficial zone protein was 3
      fold greater in the superficial zone population than in the growth zone
      population (p < 0.01). This, along with histological evidence, indicates that
      surface abrasion is successful as a zonal separation technique. Additionally,
      type II collagen was expressed 8-fold more abundantly in the growth zone than in
      the superficial zone (p < 0.005). There was no difference in aggrecan expression
      between the two zones. Regional variations among the femoral groove and medial
      and lateral condyles were also examined. No significant variations in SZP, type
      II collagen, or aggrecan were found, which makes the pooling of zonal cells from
      different regions an acceptable option for tissue engineering studies.

PMID- 15475196
TI  - Expression of bone morphogenetic proteins, receptors, and tissue inhibitors in
      human fetal, adult, and osteoarthritic articular cartilage.
AB  - Coordinate expression of BMPs and their receptors and inhibitors is likely
      necessary for physiologic BMP regulation and activity. To characterize the
      expression of such factors in fetal, normal adult, and end-stage osteoarthritic
      articular cartilage, samples from these sources were analyzed. PCR-amplified
      sequences (BMPs 1-11), receptors (IA, IB, II), TGF-beta1, TGF-beta2, inhibitors
      noggin and follistatin, CDMP-1, COMP, and GAPDH from cDNAs generated from
      extracted total RNA were resolved by gel electrophoresis. Protein levels of BMPs
      3, 7, and 8 were also analyzed by SDS-PAGE and Western blotting. RT-PCR revealed
      that BMPs 1, 2, 4-6, and 11, BMPR-IA and II, noggin, follistatin, CDMP-1, COMP,
      and GAPDH mRNAs were expressed in similar fashion in both fetal and adult (normal
      or osteoarthritic) cartilage. BMPs 9 and 10 mRNAs were not expressed in either
      group. BMPs 7, 8, and BMPR-IB mRNAs were consistently expressed in fetal but not
      in adult cartilage. BMP-3 mRNA was expressed in fetal and normal adult, but not
      in osteoarthritic samples. TGF-beta1 was expressed in both adult normal and
      osteoarthritic, but not fetal, samples. Similarly, Western blotting demonstrated
      BMPs 7 and 8 to be present in fetal but not in adult samples. BMP-3 protein was
      present in fetal and adult normal samples, to a lesser extent, but absent in
      osteoarthritic cartilage.

PMID- 15475197
TI  - Anabolic and catabolic mRNA levels of the intervertebral disc vary with the
      magnitude and frequency of in vivo dynamic compression.
AB  - The goal of this study was to characterize the anabolic and catabolic mRNA
      response of the disc to dynamic loading to determine if variations in the
      magnitude and/or frequency of loading could elicit different cellular responses.
      Sixty-eight Wistar rats were instrumented with an Ilizarov-type device spanning
      caudal disc 8-9. Seventy-two hours after surgery, animals were anesthetized and
      loaded at either 1 or 0.2 MPa at a frequency of 1, 0.2 or 0.01 Hz for 2 h (6
      groups). The surgical control (Sham) animals underwent anesthesia with no
      loading. Loaded (c8-9) and internal-control discs (c6-7 and c10-11) were
      dissected and annulus and nucleus tissue were separately analyzed by real-time RT
      PCR for levels of anabolic (collagen-1A1, collagen-2A1, aggrecan) and catabolic
      (MMP-3, MMP-13, ADAMTs-4) mRNA. In the nucleus, a frequency-dependent response
      was seen at 1 MPa with anabolic genes stimulated at 0.01 Hz and catabolic genes
      at 1 Hz. In the annulus all frequencies resulted in significant up-regulation of
      catabolic mRNA at 1 MPa loading. In general loading at 0.2 MPa or 0.2 Hz had
      little effect on gene expression. The results suggest that gene expression of the
      annulus appears to be more dependent on the magnitude of applied stress, while
      the nucleus is both magnitude- and frequency-dependent.

PMID- 15475198
TI  - Experimental ischemia of porcine growth cartilage produces lesions of
      osteochondrosis.
AB  - Osteochondrosis is a disorder of growth cartilage in which a focal failure of
      blood supply has been proposed as an important initiating factor. In the present
      study we investigated the effect on epiphyseal growth cartilage of experimentally
      interrupting the blood supply to a limited area of the distal femur of growing
      pigs. In 12 pigs, a thin full-thickness cartilage slab was removed from the
      abaxial margin of the medial condyle, thereby transecting a limited number of
      cartilage canals. The pigs were culled 1, 2, 3, 7, 14, 21 and 29 days post
      surgery. The condylar cartilage was studied histologically, immunohistologically
      and by use of the TUNEL method. The transection induced cellular death of
      cartilage canal elements followed by cellular death of chondrocytes within the
      deep layers of the resting zone of the epiphyseal growth cartilage. However, in
      the superficial layers of the resting zone, chondrocytes appeared to proliferate
      into and subsequently chondrify some of the necrotic cartilage canals. The dying
      and dead cells were TUNEL-positive, but active caspase 3-negative. The loss of
      vascular supply induced increased VEGF-immunostaining in chondrocytes surrounding
      the affected area. We conclude that transection of cartilage canals produces
      chondronecrosis in the deep resting zone of the epiphyseal growth cartilage
      similar to that observed in spontaneously occurring osteochondrosis.

PMID- 15475199
TI  - Hyaline cartilage degenerates after autologous osteochondral transplantation.
AB  - OBJECTIVES: Autologous osteochondral grafting is a well-established clinical
      procedure to treat focal cartilage defects in patients, although basic research
      on this topic remains sparse. The aim of the current study was to evaluate (1)
      histological changes of transplanted hyaline cartilage of osteochondral grafts
      and (2) the tissue that connects the transplanted cartilage with the adjacent
      cartilage in a sheep model. METHOD: Both knee joints of four sheep were opened
      surgically and osteochondral grafts were harvested and simultaneously
      transplanted to the contralateral femoral condyle. The animals were sacrificed
      after three months and the received knee joints were evaluated histologically.
      RESULTS: Histological evaluation showed a complete ingrowth of the osseous part
      of the osteochondral grafts. A healing or ingrowth at the level of the cartilage
      could not be observed. Histological evaluation of the transplanted grafts
      according to Mankin revealed significantly more and more severe signs of
      degeneration than the adjacent cartilage, such as cloning of chondrocytes and
      irregularities of the articular surface. CONCLUSION: We found no connecting
      tissue between the transplanted and the adjacent cartilage and histological signs
      of degeneration of the transplanted hyaline cartilage. In the light of these
      findings, long-term results of autologous osteochondral grafts in human beings
      have to be followed critically.

PMID- 15475200
TI  - Stem cell repair of physeal cartilage.
AB  - To evaluate the ability of cultured mesenchymal stem cells (MSC) to repair
      physeal defects, MSC-matrix constructs with 5% gelatin (group A), 10%
      gelatin/Gelfoam (Pharmacia, Peapack, NJ) (group B), and MSC grown in the presence
      of TGF-beta3 with Gelfoam (group C) were implanted in proximal tibial physeal
      defects created in 20 immature rabbits. Control groups (untreated partial defect
      and partial defect treated with Gelfoam) showed bony bar formation with varus
      deformities of 30 degrees and 28 degrees, respectively. Group A had an average 23
      degrees varus deformity with bony bridge formation, and group B had mild varus
      angulation (average 14 degrees) of the proximal tibia. In group C, there was no
      significant varus deformity (average 9 degrees), and histologic examination
      showed that some of the columnation areas interspersed with chondrocytes were
      irregularly arranged in the matrix. These findings suggest that repair of physeal
      defects can be enhanced by the implantation of MSC cultured with TGF-beta3.

PMID- 15475201
TI  - Shoulder prostheses treating cuff tear arthropathy: a comparative biomechanical
      study.
AB  - Painful cuff tear arthropathy (CTA) affects the independence of the elderly.
      Surgical treatment often consists of joint replacement, the functional outcome of
      which remains variable. Knowledge of the biomechanical properties of the
      different prosthetic designs can guide the orthopaedic surgeon in the choice of
      implant to predict its clinical result. A 3-D computer model of the glenohumeral
      joint is used to analyse the moment of the deltoid muscle in the scapular plane.
      A geometrical 3-D ball-and-socket model of the shoulder joint was used to
      calculate (1) the angle-force relationships, (2) the moment arm of the deltoid
      muscle and (3) the moment of the deltoid muscle components, for increasing
      degrees of arm elevation in the scapular plane. In this 3-D model, a clinical
      thoraco-scapular rhythm analysis was implemented, based on measurements in normal
      subjects, patients treated with an anatomical prosthesis and patients treated
      with an inversed delta III prosthesis. These data were compared for 10 different
      prosthetic treatment options. RESULTS: Muscle angle-force curves show a
      favourable slope in non-anatomical prosthetic designs, where the centre of
      rotation of the glenohumeral joint is medialized, the deltoid muscle is elongated
      and the humeral shaft is lateralized. On the contrary, anatomical prosthetic
      designs do not perform well in this computer analysis. CONCLUSIONS: From a
      biomechanical point of view, a shoulder prosthesis which medializes the centre of
      rotation, lengthens the deltoid muscle and increases the deltoid lever arm,
      results in a significantly more powerful abduction of the shoulder, despite
      complete loss of rotator cuff function. RELEVANCE: This study explains why a
      successful functional outcome can be expected in CTA with a reversed prosthesis.

PMID- 15475202
TI  - In vitro biocorrosion of Co-Cr-Mo implant alloy by macrophage cells.
AB  - We hypothesized that macrophage cells and their released reactive chemical
      species (RCS) affect Co-Cr-Mo alloy's corrosion properties and that alloy
      corrosion products change macrophage cell behavior. A custom cell culture
      corrosion cell was used to evaluate how culture medium, cells, and RCS altered
      alloy corrosion in 3-day tests. Corrosion was evaluated by measuring total charge
      transfer at a constant potential using a potentiostat and metal ion release by
      atomic emission spectroscopy. Viability, proliferation, and NO (nitric oxide) and
      IL-1beta (interlukin-1beta) release were used to assess cellular response to
      alloy corrosion products. In the presence of activated cells, total charge
      transfers and Co ion release were the lowest (p < 0.05). This was attributed to
      an enhancement of the surface oxide by RCS. Cr and Mo release were not different
      between cells and activated cells. Low levels of metal ions did not affect cell
      viability, proliferation, or NO release, though IL-1beta released from the
      activated cells was higher on the alloy compared to the controls. These data
      support the hypothesis that macrophage cells and their RCS affect alloy
      corrosion. Changes in alloy corrosion by cells may be important to the
      development of host responses to the alloy and its corrosion products.

PMID- 15475203
TI  - Effect of cortical thickness and cancellous bone density on the holding strength
      of internal fixator screws.
AB  - Internal fixators are a new class of implants designed to preserve the periosteal
      blood supply of the bone. In contrast to conventional plate fixation in which the
      screws have spherical heads and are loaded mainly by axial pullout forces, screws
      in internal fixators are "locked" within the plate and therefore subjected to
      axial as well as bending loads. In this study the ultimate loads of screws of a
      commercially available internal fixator system were tested in a pullout (n = 72)
      and cantilever bending mode (n = 72) in metaphyseal and diaphyseal regions of
      four pairs of human tibiae with different bone qualities. Cortical thickness and
      cancellous bone density were determined at the screw insertion sites. Stepwise
      multiple linear regression revealed that cortical thickness and cancellous
      density can explain 93% and 98% of the variance of the ultimate load of the
      screws in an axial pullout and cantilever bending mode. Screws in internal
      fixators are better suited to transmit shear forces and thereby make better use
      of the strength potential of bone than screws used in conventional plate
      fixation: this is especially advantageous when bone strength is reduced, e.g. due
      to osteoporosis.

PMID- 15475204
TI  - Stress relaxation of bone significantly affects the pull-out behavior of pedicle
      screws.
AB  - The initial fixation strength of pedicle screws is commonly tested using a
      standard pull-out test with load applied at a constant rate. This method
      overlooks the cyclic nature of in situ loading responsible for clinical failure.
      This study was undertaken to determine the effects of stress relaxation
      properties at the bone-screw interface on screw fixation strength. Pedicle screws
      were inserted into calf lumbar vertebrae using a paired testing array. After
      embedding and mounting in a custom fixture, axial pull-out tests were performed
      at the rates of 1, 5, and 25 mm/min. For each vertebra, one screw was pulled at a
      continuous rate. The other screw was pulled at increments of 0.5 mm, at the same
      rate, with 1000 s pause between increments. Peak load, energy-to-failure,
      displacement-to-failure, and stiffness were calculated for each screw pull-out
      test. Two-way ANOVA showed that the standard pull-out method yielded
      significantly higher peak loads (p < 0.05) at faster pull-out rates and higher
      stiffnesses (p < 0.05) at all rates compared to the stress relaxation pull-out
      protocol. These results suggest that the stress relaxation properties of bone
      significantly affect the pull-out behavior of pedicle screws, reducing the peak
      load and stiffness values observed during testing. This mode of testing may
      provide a better biomechanical model of screw pull-out failure and a more
      accurate estimate of initial fixation strength.

PMID- 15475205
TI  - Effects of rotation on measurement of lower limb alignment for knee osteotomy.
AB  - The purposes of this study were to clarify the effects of rotation on two
      dimensional measurement of lower limb alignment for knee osteotomy using a three
      dimensional method and to determine whether this 3-D simulation method could help
      with planning of knee osteotomy. We developed computer software to calculate
      femorotibial angle (FTA) and hip-knee-ankle angle (HKA) and simulate knee
      osteotomy from a CT-based 3-D bone model of the lower limb. Lower limb rotation
      on anteroposterior long-standing radiographs was measured by superimposing the 3
      D bone models. Changes in alignment with limb rotation were calculated using the
      software. FTA after virtual closed-wedged osteotomy was measured for a
      hypothetical case of a rotation error of the osteotomy plane in reattaching the
      proximal cutting surface to the distal cutting surface. For 31 varus knees in 20
      patients with medial compartment arthritis, the mean rotation angle, relative to
      the epicondylar axis, with variable limb position was 7.4 +/- 3.9 degrees of
      internal rotation (mean +/- SD), ranging from 8 degrees of external rotation to
      14 degrees of internal rotation; the mean changes in FTA and HKA were 3.5 +/- 2.2
      degrees (range, 0.4-8.6) and 1.6 +/- 1.3 degrees (range, 0.2-4.9), respectively.
      The FTA "flexion angle" (lateral view alignment from neutral AP) and the absolute
      HKA "flexion angle" correlated with the change in FTA and HKA with limb rotation,
      respectively (FTA, R = 0.999; HKA, R = 0.993). The mean change in FTA after
      virtual closed-wedged osteotomy was 3.2 degrees for internal and external 10
      degrees rotation errors in reattaching the osteotomy plane. Rotation may affect
      measurement of lower limb alignment for knee osteotomy, and 3-D methods are
      preferable for surgical planning.

PMID- 15475206
TI  - A novel murine segmental femoral graft model.
AB  - To further understand the cellular and molecular mechanisms underlying cortical
      bone graft healing, we have developed a novel mouse femur model that permits
      quantitative and molecular analysis of structural bone graft healing. A 4 mm mid
      diaphyseal femoral segment was removed and replaced by either immediate
      implantation of a fresh autograft, a frozen, genetically identical isograft or a
      frozen allograft from a different strain of mouse, which was secured with a 22
      gauge metal intramedullary pin. Healing was evaluated by radiology,
      histomorphometry, and in situ hybridization. Autograft repair occurred by
      endochondral bone formation at the host-graft junction and by intramembranous
      bone formation along the length of the graft bed at 2 weeks, with maturation and
      remodeling apparent by 4 weeks. Bone repair in allografts and isografts
      completely relied on endochondral bone formation at the host-graft cortical
      junction, with absence of periosteal bone formation along the length of the
      graft, suggesting that live periosteal cells from the donor tissue are necessary
      for this response. This small animal model of structural bone grafting can be
      used to evaluate tissue-engineered allografts and novel bone graft substitutes
      using quantitative and molecularly defined outcome measures.

PMID- 15475207
TI  - Adenoviral-mediated transfer of human BMP-6 gene accelerates healing in a rabbit
      ulnar osteotomy model.
AB  - This study evaluated healing of rabbit bilateral ulnar osteotomies 6 and 8 weeks
      after surgery in response to percutaneous injection of transgenic adenoviral (Ad)
      bone morphogenetic protein-6 (BMP-6) vector or green fluorescent protein vector
      control (Ad-GFP) administered 7 days after surgery compared to untreated
      osteotomy controls. The amount, composition and biomechanical properties of the
      healing bone repair tissue were compared among groups and to historical data for
      intact rabbit ulnae obtained from similar studies at the same institution.
      Quantitative computed tomography was used to determine area, density and mineral
      content of the mineralized callus in the harvested ulnae. Maximum torque,
      torsional stiffness, and energy absorbed to failure were determined at 1.5
      degrees /s. Calcified sections of excised ulnae (5 microm) were stained with
      Goldner's Trichrome and Von Kossa, and evaluated for callus composition,
      maturity, cortical continuity, and osteotomy bridging. Radiographic assessment of
      bone formation indicated greater mineralized callus in the ulnae injected with Ad
      hBMP-6 as early as 1 week after treatment (2 weeks after surgery) compared to
      untreated osteotomy ulnae (p < 0.006) and Ad-GFP treated osteotomy ulnae (p <
      0.002). Quantitative computed tomography confirmed greater bone area and bone
      mineral content at the osteotomy at 6 weeks in Ad-BMP-6 treated osteotomy as
      compared to untreated osteotomy ulnae (p < 0.001) and Ad-GFP treated osteotomy
      ulnae (p < 0.01). Ad-BMP-6 treated osteotomy ulnae were stronger (p < 0.001 and
      0.003) and stiffer (p < 0.004 and 0.003) in torsion at 6 weeks than untreated
      osteotomy ulnae or Ad-GFP treated osteotomy ulnae, respectively. Maximum torque,
      torsional stiffness, and energy absorbed to failure were greater in Ad-BMP-6
      treated osteotomy ulnae compared to their respective untreated contralateral
      osteotomy ulnae at 8 weeks [p < 0.03]. Maximum torque and torsional stiffness in
      the Ad-BMP-6 treated osteotomy ulnae were not different to intact ulnae values at
      6 and 8 weeks. These experiments confirm that BMP-6 can be potently
      osteoinductive in vivo resulting in acceleration of bone repair.

PMID- 15475208
TI  - Viable osteoblastic potential of cortical reamings from intramedullary nailing.
AB  - To analyze the effect of intramedullary reaming on fracture healing, we
      investigated whether or not cortical reamings contain viable bone cells. There
      are several tissue components contained in medullary reamings including blood,
      bone marrow and cortical bone. This study is focused on the cortical reamings,
      which are produced during reaming of the medullary cavity. They may stimulate
      fracture healing but it is still unclear if they contain vital bone cells. We
      tested the hypothesis that these cortical reamings are a source of viable bone
      cells and compared cell cultures with cultivated cells from iliac crest biopsies.
      Responses of protein content and ALP activity to vitD stimulation in the cells
      were considered as properties of viability. Ten in tact living sheep femora were
      fully reamed and the cortical reamings were cultivated in a standard manner and
      compared with cultivated cells from ipsi-lateral iliac crest biopsies from the
      same animals. Cells started to grow from the reamings as well as the iliac crest
      within 2-5 days, and covered the entire culture flask within 9-13 days. Protein
      content and ALP activity in cells from both reamings and iliac crest were
      significantly responsive to vitD stimulation. Cortical reamings from
      intramedullary nailing have osteoblastic potential and contain living bone cells
      similar to bone cells from the iliac crest. These findings may further explain
      the superior healing of fractures, treated with reamed nailing.

PMID- 15475209
TI  - Distraction osteogenesis in the Cbfa-1+/- mouse.
AB  - Distraction osteogenesis involves division of a bone and gradually pulling the
      bone ends apart. This delivers mechanical stimulation to mesenchymal cells in the
      distraction gap, where new bone is regenerated predominantly by intramembranous
      ossification. The transcription factor Cbfa1 has been reported to be essential
      for the differentiation of mesenchymal cells to osteoblasts. In homozygous Cbfa1
      knockout mice, both intramembranous and endochondral ossification mechanisms are
      blocked and no bone formation occurs. In heterozygous Cbfa1 knockout mice, only
      the cranial bones and the clavicles, which form through intramembranous
      ossification, fail to develop properly as in the human condition of
      cleidocranialdysostosis. It has been suggested, therefore, that intramembranous
      ossification is affected by the absence of one of the paired Cbfa1 genes. We have
      assessed the potential for intramembranous ossification following distraction
      osteogenesis in heterozygous Cbfa1 knockout mice. Fourteen skeletally mature male
      heterozygous mice were used, together with 10 wild-type controls. The tibia was
      distracted by 0.25 mm twice a day (0.5 mm/day) for 10 days using the half-ring
      type fixator. Nine mice were kept for a further 28 days to observe the
      consolidation phase. In four out of five mice of the heterozygous group and in
      all three wild-type mice, bony fusion within the distraction gap was observed on
      radiographs. Histological findings were almost the same in the two groups at
      various stages of the procedure and intramembranous ossification was predominant
      in both the groups. Despite the inhibition of intramembranous ossification during
      the foetal development of Cbfa1+/- mice, distraction osteogenesis was as
      successful as in control mice.

PMID- 15475210
TI  - Oscillatory fluid flow affects human marrow stromal cell proliferation and
      differentiation.
AB  - Mechanical loading is an important regulator of bone formation and bone loss.
      Decreased osteoblast number and function are important cellular mechanisms by
      which mechanical disuse leads to decreased bone formation. Decreased osteoblast
      number may be a result of decreased osteoprogenitor proliferation,
      differentiation, or both. However, the effects of cellular level physical signals
      on osteoprogenitors are not well understood. In this study, we examined the
      effects of loading induced oscillatory fluid flow (OFF), a potent regulator of
      osteoblastic cell function, on marrow stromal cells (MSCs). MSCs subjected to OFF
      exhibited increased intracellular Ca2+ mobilization. In addition, MSCs exhibited
      increased proliferation and increased mRNA levels for osteopontin and osteocalcin
      genes. Collagen I and core binding factor 1 mRNA levels did not change. MSCs
      subjected to OFF also exhibited decreased alkaline phosphatase activity. These
      results suggest that MSCs are mechanosensitive and that Ca2+ may play a role in
      the signaling pathway.

PMID- 15475211
TI  - Transduction of rabbit saphenous artery: a comparison of naked DNA, liposome
      complexes, and adenovirus vectors.
AB  - The methods and efficiency of gene transfer into rabbit saphenous artery were
      examined in this study. The purpose was to develop an animal model capable of
      evaluating the use of angiogenic gene therapy to revascularize necrotic bone more
      rapidly and completely than by surgical implantation of blood vessels alone. The
      success of transduction using adenovirus vectors, liposome/DNA complexes, and
      naked DNA was evaluated with delivery to both intra-luminal and adventitial
      sites. Intra-luminal and adventitial (extra-luminal) application was used for the
      viral and liposome methods. Naked DNA was evaluated only in the intra-luminal
      site, based upon previous reports. Relative transduction success was expressed as
      the percentage of total cells with beta-galactosidase activity. A 20-mm length of
      saphenous artery exposed surgically was targeted for lacZ gene transfer. Two days
      after transduction, the arteries were harvested and stained with X-gal for beta
      galactosidase activity. The percentage of endothelial, media and adventitial
      cells with beta-galactosidase activity was determined. Intra-arterial injection
      of adenovirus vector transduced the largest amount of cells in all three areas of
      the vessel (endothelium, media and adventitia). The adenovirus vectors when
      applied to the adventitia only transduced adventitial cells. Following intra
      arterial injection of liposome/DNA complexes transduction was detected only in
      endothelium. Extra-luminal liposome and intra-arterial naked DNA delivery
      resulted in no detectable gene transfer. Intra-arterial delivery of an adenovirus
      vector would likely provide optimal gene transfer for possible angiogenic gene
      therapy.

PMID- 15475212
TI  - Motion-based tendon diagnosis using sequence processing of ultrasound images.
AB  - Degenerative or pre-degenerative processes in the tendon, which could lead to a
      spontaneous rupture, are well known problems, especially among athletes. Existing
      non-invasive diagnostic methods are mainly based on subjective analysis of static
      images of the tendon, but in many cases the degeneration cannot be diagnosed in
      time. Combining a set of existing image processing techniques, a tool for
      tracking the in vivo motion of a tendon imaged with dynamic ultrasound was
      implemented. A group of subjects that had undergone a degenerative rupture of
      their Achilles tendon, one subject with a traumatic rupture, and a group of
      control subjects were all tested. Using the motion information that was obtained
      from both tendons of all subjects, we developed an automatic test that examines
      the symmetrical properties of the tendon's motion, and defined a negative
      asymmetry property that could be quantified as a score. This score was found to
      be significantly more enhanced in the post-operative tendons (18.0 +/- 9.0) than
      in the contra-lateral healthy tendons of the same subjects (3.9 +/- 4.6). In the
      single traumatic rupture subject, this effect was not found (0.0). This leads us
      to believe that the negative asymmetry of tendon motion may be associated with
      degenerative or pre-degenerative processes in the tendon. Also, the mean degree
      of negative asymmetry in the healthy tendons of post-operative subjects (3.9 +/-
      4.6) was found to be higher than that of healthy tendons of the control group
      (1.5 +/- 1.8). This finding may be associated with the fact that tendons that are
      contra-lateral to spontaneously ruptured tendons have a higher risk of developing
      degenerative processes. The method presented here is objective, low-cost, non
      invasive and possibly more sensitive than existing non-invasive techniques.

PMID- 15475213
TI  - Collagen fibres of the spontaneously ruptured human tendons display decreased
      thickness and crimp angle.
AB  - PURPOSE: To study collagen fibre thickness and crimp formation in healthy and
      ruptured human tendons. METHODS: The thickness, crimp angle and wavelength of the
      collagen fibres were analyzed by interference and polarization microscopy and the
      samples were studied by transmission and scanning electron microscopy in four
      different healthy human tendons (Achilles, Quadriceps, Biceps brachii and
      Extensor pollicis longus) and in 66 spontaneously ruptured tendons. RESULTS: In
      the normal (healthy) tendons, the diameter and crimp angle of the collagen fibres
      varied greatly between the four different tendons, the thickest fibres with the
      largest crimp angle being in the Achilles and Quadriceps tendons, whereas the
      Biceps brachii and Extensor pollicis longus, tendons that bear lighter strains
      but carry functions of high specificity, were found to have substantially smaller
      collagen fibres with lower crimp angle. Ruptured tendons had significantly
      smaller collagen fibre diameter than the normal tendons, the fibre diameter being
      -36% in comparison to their healthy counterparts in the Achilles tendons (P <
      0.0001), -24% in the Quadriceps tendons (P < 0.0001), -37% in the Biceps brachii
      (P < 0.0001) and -14% in the Extensor pollicis longus (P = 0.10), respectively.
      Similarly, the crimp angle of the collagen fibres was also found to be lower in
      the ruptured tendons than in healthy, normal tendons. Further, the collagen
      fibres in the ruptured human tendons showed great variation in the crimp angle
      between the adjacent fibres and in the successive crimps of the same fibre.
      CONCLUSION: Our results show that spontaneously ruptured tendons display focal
      regions with decreased collagen fibre thickness, decreased crimp angle and
      disrupted crimp continuity, microscopic alterations that possibly result in
      reduced strength of the tendons being less resistant to tensile forces, and thus,
      place them at increased risk of ruptures.

PMID- 15475214
TI  - Vascular pathologic changes in the flexor tenosynovium (subsynovial connective
      tissue) in idiopathic carpal tunnel syndrome.
AB  - We used the Verhoeff-van Gieson stain method to identify histopathology and to
      localize elastin in the subsynovial connective tissue of the tendon sheath (SSCT)
      of the middle finger flexor digitorum superficialis (FDS) within the carpal
      tunnel in 10 carpal tunnel syndrome (CTS) patients and 10 control cadaver
      specimens. Normal SSCT stained for elastin abundantly around blood vessels and
      within vessel walls. The typical pathologic findings of CTS patients SSCT
      included vascular proliferation, vascular hypertrophy, and vascular obstruction
      with wall thickening. There was a decreased amount of elastin in the blood vessel
      walls and around the vessels in the CTS patients as well. The changes in the
      carpal tunnel patients were particularly remarkable in that the patients were
      younger than the controls, yet showed findings more characteristic of chronic
      degeneration.

PMID- 15475215
TI  - A histomorphological study of tendon reconstruction to a hydroxyapatite-coated
      implant: regeneration of a neo-enthesis in vivo.
AB  - The attachment of tendons and ligaments to massive endoprostheses remains a
      clinical challenge due to the difficulty in achieving a soft tissue implant
      interface with a mechanical strength sufficient to transmit the forces necessary
      for locomotion. We have used an in vivo animal model to study patellar tendon
      attachment to an implant surface. The interface generated when the patellar
      tendon was attached to a hydroxyapatite (HA) coated implant was examined using
      light microscopy and a quantitative histomorphological analysis was performed. In
      the Autograft Group, the interface was augmented with autogenous cancellous bone
      and marrow graft, and at six weeks an indirect-like insertion was observed. At
      twelve weeks, the interface was observed to be a layered neo-enthesis, whose
      morphology was similar to a normal direct tendon insertion. In the HA Group, the
      tendon-implant interface was not augmented, and the implant was enveloped by a
      dense collagenous fibrous tissue. This study shows that a tendon-implant neo
      enthesis can develop in situ by employing a suitable implant surface in
      association with biological augmentation.

PMID- 15475216
TI  - Properties of the two neuromuscular compartments in a split bipennate muscle.
AB  - Bipennate muscles may be split along their distal aponeurosis, dividing each into
      two compartments. These sub-muscle units may be used in tendon transfers. This
      paper presents the contractile properties of the two sub-units of the flexor
      carpi ulnaris in a macaca fascicularis, after it was split by up to 80% of its
      length. The sub-muscle units were electrically stimulated and found to have
      independent isometric contraction, with minimal contraction recorded from the non
      stimulated sub-unit. Also, the sum of the forces measured from each unit when
      stimulated individually, was found to be greater than the force of the whole
      muscle, given the same isometric conditions. The distal aponeurosis which is
      common allows force transmission between the compartments. Splitting the muscle
      along this distal aponeurosis alters this function and the force capacity of the
      muscle, providing a new potential for using the sub-units as grafts for tendon
      transfers.

PMID- 15475217
TI  - Overstretching of sarcomeres may not cause cerebral palsy muscle contracture.
AB  - To answer the question whether the muscle contracture in patients with cerebral
      palsy is caused by overstretching of in-series sarcomeres we studied the active
      and passive force-length relationship of the flexor carpi ulnaris muscle (FCU) in
      relation to its operating length range in 14 such patients with a flexion
      deformity of the wrist. Force-length relationship was measured intra-operatively
      using electrical stimulation, a force transducer, and a data-acquisition system.
      Muscle length was measured in maximally flexed and maximally extended position of
      the wrist. The spastic FCU was found to exert over 80% of its maximum active
      force at maximal extension of the wrist and this indicates abundant overlap of
      the sarcomeres. At maximal wrist extension, FCU passive force corresponded with
      only 0.7-18% of maximum active force. Both findings imply that the FCU sarcomeres
      are not overstretched when the wrist is extended. We conclude that the
      overstretching of in-series sarcomeres appears not to be the cause of contracture
      of the spastic FCU.

PMID- 15475218
TI  - Production of consistent crush lesions in murine quadriceps muscle--a
      biomechanical, histomorphological and immunohistochemical study.
AB  - Poor healing of high-energy fractures is often associated with severe muscle
      damage. This may be partly due to the production, by the injured muscle, of
      inflammatory cytokines that somehow misdirect bone healing. In order to
      investigate this question, an animal model was established which embodies a
      controlled degree of muscle injury with a dose response to the energy absorbed,
      that can be characterised histologically. Using a custom crush jig, 60 CFLP mice
      had either 100 or 200 g masses dropped from a fixed height onto the quadriceps
      muscle, with mechanical measurement of the impact. Energy of impact was reliably
      and significantly different between the small and large impact conditions, though
      there was more variability when the large mass was used. Animals were sacrificed
      at day 2, 4, 8, 16, and 24 post-injury. Muscle histomorphometry at all time
      points and immunohistochemistry for IL-1beta, IL-6, and TNF-alpha up to day 8
      were used as measures of muscle damage, inflammation and repair. Histological
      sections were analysed into areas of normal muscle fibres, damaged/regenerating
      muscle fibres and fibrous/inflammatory infiltrate. Early histological response
      was similar between the two groups; the large crush group displayed significantly
      greater areas of inflammatory infiltrate and damaged muscle at the later time
      points after day 8. In the large crush group, IL-1beta and IL-6 expression were
      significantly higher at day 2 and TNF-alpha was higher at day 8 when compared to
      the small crush group. The experiment demonstrated that more severe injury to
      muscle was reliably followed by increased inflammatory cytokine production and a
      greater degree of inflammation and fibrosis. Increased production of inflammatory
      cytokines such as TNF-alpha and IL-1beta in the damaged muscles may activate
      macrophages and recruit fibroblasts, promote scar formation and lead to delayed
      union or non-union of the adjacent fracture(s).

PMID- 15475219
TI  - Neuronal regeneration after application of radiofrequency energy to collagenous
      tissue is affected by limb immobilization: an in vivo animal study.
AB  - Despite widespread use of radiofrequency (RF)-shrinkage, there have been no
      studies on the influence of RF-energy on neural elements of collagenous tissue.
      The purpose of this study was to examine the effect of RF-shrinkage on neural
      structures of capsuloligamentous tissue and the recovery of neural elements under
      different postoperative treatment protocols. One patellar tendon of 46 New
      Zealand-White rabbits was shrunk. Six rabbits were sacrificed immediately
      postoperative. Twenty rabbits were not immobilized, 10 were immobilized for 3 and
      10 were immobilized for 6 weeks. A monoclonal antibody, specific against a
      neurofilament protein, was used to detect nerves and neural structures. Staining
      pattern of nerve fibres was significantly altered immediately postoperative.
      After 3 weeks the number of nerve fibres and bundles decreased significantly in
      immobilized and non-immobilized limbs. The loss of nerve fibres was significantly
      less in immobilized limbs. At 6 weeks the number of neural elements in
      immobilized limbs increased to the level of untreated control tissue. In non
      immobilized limbs we found no recovery of neural elements 9 weeks
      postoperatively. At this time the number of nerve fibres and bundles was still
      significantly less compared to the untreated control limbs. RF-shrinkage causes
      significant alteration of neural elements. Under immobilization nerve fibres and
      bundles reach the level of normal untreated tissue. Careful rehabilitation is
      important after RF-shrinkage. Not only for biomechanical reasons, but also to
      allow the neural elements to recover, thermally modified tissue should be
      protected from normal physiologic loads.

PMID- 15475220
TI  - Prevention and treatment of experimental osteomyelitis in dogs with ciprofloxacin
      loaded crosslinked high amylose starch implants.
AB  - Crosslinked high amylose starch (CLHAS) matrix was used as a biodegradable drug
      delivery implant for the prevention and treatment of osteomyelitis. Thirty-two
      dogs underwent the femoral insertion of a screw inoculated with Staphylococcus
      aureus and were then randomly assigned to four groups: (A) prevention with
      ciprofloxacin-CLHAS implants, (B) surgical debridement (positive control), (C)
      surgical debridement and oral ciprofloxacin treatment and (D) surgical
      debridement and treatment with ciprofloxacin-CLHAS implants. At week 4 the
      osteomyelitis was confirmed, the infected site debrided and respective treatments
      initiated for groups B, C and D. Radiographs, macroscopic evaluations, bacterial
      cultures and histopathological examinations were used to evaluate the femora at
      week 10. Femora from preventive group A were almost normal. Dogs of both
      ciprofloxacin treatment groups C and D showed better bone healing, less
      periosteal reaction and less screw mobility than dogs from group B. Eradication
      of infection was observed at proximal/distal sites in B: 25%/12%, C: 37%/62% and
      D: 62%/75%. Both ciprofloxacin treated groups improved radiographically from week
      4 to week 10. Periosteal and marrow neutrophilic and lymphoplasmocytic
      infiltrations were less severe in groups C and D versus group B. These data
      suggest that biodegradable ciprofloxacin-CLHAS implants are a safe and efficient
      modality for the prevention and treatment of osteomyelitis.

PMID- 15475221
TI  - Viruses adsorbed on musculoskeletal allografts are inactivated by terminal
      ethylene oxide disinfection.
AB  - In 1987 it was anticipated that unsterilized tissues would transmit virus
      diseases such as hepatitis and HIV-1 from infected donors so a freeze-drying
      process for musculoskeletal tissue was developed to include terminal ethylene
      oxide (EO) exposure for 14 h. We found no studies of EO efficacy when viruses
      were associated with human allografts so we studied the antiviral effect of
      terminal EO disinfection using all but the final freeze-drying phase of this
      clinical processing protocol (CPP). Specifically we looked at EO inactivation of
      HIV-1, a human hepatitis B surrogate and test viruses known to be highly
      resistant to disinfecting agents, including irradiation. Freeze-drying,
      ordinarily required after EO disinfection and part of the CPP, was not done.
      Suspensions of HIV-1, Bovine viral diarrhea, Reovirus type 3, Duck hepatitis B,
      Poliomyelitis and Canine parvovirus were adsorbed on glass, demineralized bone
      powder, and preprocessed strips of femoral cortex, iliac wedges, cancellous
      blocks and patellar bone-tendon-bone preparations and subjected to EO
      disinfection. Test viruses were inactivated at the end of 7 h of EO disinfection,
      providing a safety factor in the CPP of at least 100%. Because allografts can
      transmit viruses, terminal EO disinfection should provide safer musculoskeletal
      allografts than non-disinfected tissues or those irradiated with a standard
      irradiation dose. New spontaneously appearing viruses would probably be
      inactivated with this terminal EO disinfection but they and viral bioweapons will
      require individual validation to assure viral inactivation.

PMID- 15475222
TI  - "Extracorporeal shock wave therapy for plantar fasciitis--a double blind
      randomised controlled trial" by C.A. Speed et al., J Orthop Res 2003;21:937-40.

PMID- 15475223
TI  - "Extracorporeal shock wave therapy for plantar fasciitis--a double blind
      randomised controlled trail" by C.A. Speed et al., J Orthop Res 2003;21:937-40.

PMID- 15475226
TI  - Obesity: the worldwide epidemic.
AB  - Over the last decade, the prevalence of obesity in Western and Westernizing
      countries has more than doubled. A standardized classification of overweight and
      obesity, based on the body mass index now allows a comparison of prevalence rates
      worldwide for the first time. In children, the International Obesity Taskforce
      age, sex, and BMI specific cut-off points are increasingly being used. BMI data
      are being evaluated as part of a new analysis of the Global Burden of Disease.
      Prevalence rates for overweight and obese people are very different in each
      region with the Middle East, Central and Eastern Europe and North American having
      higher prevalence rates. Obesity is usually now associated with poverty even in
      developing countries. Relatively new data suggest that abdominal obesity in
      adults, with its associated enhanced morbidity, occurs particularly in those who
      had lower birth weights and early childhood stunting.

PMID- 15475227
TI  - How do we get fat? An epidemiologic and metabolic approach.
AB  - Obesity results when the energy intake exceeds expenditure for a long period. The
      first law of thermodynamics, which describes this relationship, does not provide
      insight into the failures to couple energy intake and expenditure. Research over
      the past two decades has provided an unprecedented expansion of knowledge about
      the physiological and molecular mechanisms regulating body fat. Perhaps the
      greatest impact has resulted from the cloning of genes corresponding to the five
      mouse monogenic obesity syndromes and the subsequent characterization of the
      human counterparts to these syndromes. Extensive molecular and reverse genetic
      studies (mouse knockouts) have helped establish other critical pathways that
      regulate body fat and food intake, and also have either validated or refuted the
      importance of previously identified pathways.

PMID- 15475228
TI  - Insulin resistance and obesity.
AB  - Obesity, particularly central obesity, is associated with insulin resistance.
      Much research has focused on mechanisms that link obesity to insulin resistance,
      including lipid accumulation in muscle and liver and the recently discovered
      adipocytokines. Insulin resistance is an important feature of a number of common
      conditions, including type 2 diabetes and polycystic ovary syndrome and is
      associated with rarer disorders, such as inherited insulin receptoropathies and
      genetic and acquired lipodystrophies. Despite its use for a number of years,
      metformin's role as an insulin sensitizer has only recently been appreciated. The
      discovery of a new class of insulin sensitizing agents, the thiazolidinediones,
      represents a major advance in the understanding of the etiology of insulin
      resistance, particularly in relation to adipocyte biology and possibly, its
      inflammatory origins.

PMID- 15475229
TI  - Medical consequences of obesity.
AB  - The obese are subject to health problems directly relating to the carriage of
      excess adipose tissue. These problems range from arthritis, aches and pains,
      sleep disturbance, dyspnea on mild exertion, and excessive sweating to social
      stigmatization and discrimination, all of which may contribute to low quality of
      life and depression (Table 1). The most serious medical consequences of obesity
      are a result of endocrine and metabolic changes, most notably type 2 diabetes
      mellitus, cardiovascular disease, and increased risk of cancer. Not all obesity
      comorbidities are fully reversed by weight loss. The degree and duration of
      weight loss required may not be achievable by an individual patient. Furthermore,
      "weight cycling" may be more detrimental to both physical and mental health than
      failure to achieve weight loss targets with medical and lifestyle advice.

PMID- 15475230
TI  - Obesity and dermatology.
AB  - Obesity is associated with a number of dermatoses. It affects cutaneous
      sensation, temperature regulation, foot shape, and vasculature. Acanthosis
      nigricans is the most common dermatological manifestation of obesity. Skin tags
      are more commonly associated with diabetes than with obesity. Obesity increases
      the incidence of cutaneous infections that include: candidiasis, intertigo,
      candida folliculitis, furunculosis, erythrasma, tinea cruris, and folliculitis.
      Less common infections include cellulitis, necrotizing fasciitis, and gas
      gangrene. Leg ulcerations, lymphedema, plantar hyperkeratosis, and striae are
      more common with obesity. Hormonal abnormalities and genetic syndromes (Prader
      Willi) are related to obesity and its dermatoses; however, cellulite is not
      related to obesity.

PMID- 15475231
TI  - Dietary approaches to overweight and obesity.
AB  - For years dietary guidelines for the treatment of overweight and obesity have
      advised a low-fat, high carbohydrate diet. Recent meta-analyses have shown that
      weight loss achieved with ad libitum low-fat diets is typically in the range of 3
      4 kg. Although clinically significant, this weight loss is modest, usually
      regained on cessation of the intervention and the low-fat messages have not
      impacted on the ever increasing rates of overweight and obesity. Alternative
      approaches include low-glycemic index and high protein diets. Both effectively
      reduce the glycemic load of the diet and early studies suggest they may be
      effective in increasing satiety, reducing ad libitum energy intake and may
      improve fat oxidation by reducing insulin demand. Both approaches can be used
      within the context of a reduced-fat diet, with evidence emerging to suggest this
      may improve weight and body composition outcomes.

PMID- 15475232
TI  - Physical activity in the management of obesity.
AB  - Physical activity is any movement of skeletal muscles that results in energy
      expenditure. Long-term success in weight management depends on both physical
      activity and dietary modification. Exercise has a pivotal role in weight
      management, optimising body composition by minimising fat-free mass losses and
      maximising fat mass loss; and, enhancing metabolic fitness. The amount and type
      of exercise needed to obtain health-related benefits may differ from that
      recommended for fitness benefits. Public health messages about exercise have
      focused on improvements in general health and fitness rather than on weight loss,
      prevention of weight gain or weight regain. About 2.5 times more exercise than
      the US Surgeon General's recommendation is needed to maintain energy balance and
      thus maintain a certain weight. The challenge is to get the exercise prescription
      right at an individual level.

PMID- 15475233
TI  - Pharmacotherapy of obesity.
AB  - Whereas several drugs to treat most other chronic conditions have been developed
      over the last 30 years, progress in pharmacologic therapy for obesity has been
      slow. The record of drug treatment for obesity partly explains this phenomenon
      and is of concern. Several compounds have been withdrawn when severe side effects
      have been discovered. The lack of scientifically developed safe and effective
      antiobesity drugs has opened the gates for an enormous number of commercial
      products that make vast sums of money, but have no scientific evidence backing
      their efficacy. This pattern is seen in both developed and developing countries.
      summarizes some of the presently accepted, scientifically evaluated antiobesity
      drugs. At present, orlistat and sibutramine are the only two major drugs used
      almost worldwide.

PMID- 15475234
TI  - Bariatric surgery.
AB  - At present, surgery is necessary to counter extreme obesity. The outcomes in
      bariatric surgery have improved steadily and today most co-morbidities in the
      massively overweight can be improved or even resolved by surgery. The procedures
      work in one of two ways; by restricting the patient's ability to eat or by
      interfering with the ingested nutrient absorption. The operative treatment is in
      no way cosmetic. Drawbacks to the surgical therapy exist; major life-long
      rearrangement of the gastrointestinal tract, an operative mortality (<0.5%) and
      morbidity (about 10%). Surgically induced weight loss is currently the most
      effective treatment for the severely obese patient.

PMID- 15475235
TI  - Psychological aspects of obesity.
AB  - Obesity is a complex condition associated with a host of medical disorders. A
      common assumption is that obesity must also be related to psychological and
      emotional complications. Research on the psychosocial aspects of obesity has
      grown more sophisticated over the years, from purely theoretical papers to cross
      sectional comparisons of people with and without obesity to prospective
      investigations of the temporal sequence of obesity and mood disturbance. These
      studies have shown that obesity, by itself, does not appear to be systematically
      associated with psychopathological outcomes. Certain obese individuals, however,
      are at greater risk of psychiatric disorder, especially depression. The present
      paper reviews the research findings and presents their clinical implications.
      Chiefly, treatment providers should not assume that a depressed or otherwise
      disturbed obese person needs only to lose weight in order to return to
      psychological health. Significant mood disturbances should be treated equally
      aggressively, regardless of a patient's weight status.

PMID- 15475236
TI  - Special considerations in childhood and adolescent obesity.
AB  - Child and adolescent obesity is increasingly prevalent in westernized countries.
      It is associated with significant medical and psychosocial co-morbidities that
      are both immediate and long-term. While genetic factors influence the
      susceptibility of a given child to an obesity-conducive environment, the current
      epidemic is due to massive environmental change over the past few decades leading
      to a rise in sedentary pursuits, a decrease in physical activity and increased
      energy intake. Effective management requires a family-focused, developmentally
      sensitive, behavioural management approach that addresses, for example, eating
      habits, incidental activity and television viewing. Prevention of childhood
      obesity will ultimately require multi-faceted, large-scale interventions.

PMID- 15475237
TI  - Mouse models of obesity.
AB  - Insights into the etiology of human obesity have arisen from the study of animal
      models. Animal models of obesity are also important for the development of future
      treatments of obesity. An agouti mouse mutation resulting in obese, yellow mice
      was described over a century ago and in 1992 agouti was cloned, making it the
      first obesity gene characterized at the molecular level. The lethal yellow mouse
      mutation is one of five dominant agouti mutations and is an excellent model for
      human obesity. The molecular categorization of agouti was responsible for the
      elucidation of the melanocortin system's involvement in hypothalamic weight
      regulation. As genetic knowledge increases many transgenic mice have been created
      with genes either over-expressed or deleted, models which further enhance the
      understanding of obesity.

PMID- 15475239
TI  - Estimation of genotype error rate using samples with pedigree information--an
      application on the GeneChip Mapping 10K array.
AB  - Currently, most analytical methods assume all observed genotypes are correct;
      however, it is clear that errors may reduce statistical power or bias inference
      in genetic studies. We propose procedures for estimating error rate in genetic
      analysis and apply them to study the GeneChip Mapping 10K array, which is a
      technology that has recently become available and allows researchers to survey
      over 10,000 SNPs in a single assay. We employed a strategy to estimate the
      genotype error rate in pedigree data. First, the "dose-response" reference curve
      between error rate and the observable error number were derived by simulation,
      conditional on given pedigree structures and genotypes. Second, the error rate
      was estimated by calibrating the number of observed errors in real data to the
      reference curve. We evaluated the performance of this method by simulation study
      and applied it to a data set of 30 pedigrees genotyped using the GeneChip Mapping
      10K array. This method performed favorably in all scenarios we surveyed. The dose
      response reference curve was monotone and almost linear with a large slope. The
      method was able to estimate accurately the error rate under various pedigree
      structures and error models and under heterogeneous error rates. Using this
      method, we found that the average genotyping error rate of the GeneChip Mapping
      10K array was about 0.1%. Our method provides a quick and unbiased solution to
      address the genotype error rate in pedigree data. It behaves well in a wide range
      of settings and can be easily applied in other genetic projects. The robust
      estimation of genotyping error rate allows us to estimate power and sample size
      and conduct unbiased genetic tests. The GeneChip Mapping 10K array has a low
      overall error rate, which is consistent with the results obtained from
      alternative genotyping assays.

PMID- 15475240
TI  - A comparison of gene expression profiles produced by SAGE, long SAGE, and
      oligonucleotide chips.
AB  - A comparison study of short SAGE versus GeneChip and long SAGE was conducted to
      determine if data were interchangeable between the techniques. Although SAGE and
      Affymetrix chip expression levels showed a significant correlation using the set
      of genes for which there was reliable and unambiguous mapping from tag-to-gene
      identification, correlation coefficients were low (0.51 for the Spearman's
      correlation coefficient with p < 0.0001). A quantitative analysis comparing the
      use of 10-bp SAGE tags to 17-bp SAGE tags indicated that the short SAGE
      technology was more efficient at identifying differentially expressed tags.
      However, 4-7% of the 10-bp tags were redundancies that could have been resolved
      by long SAGE and 10-20% of the short SAGE tags had no obvious match to currently
      annotated human transcript sequences.

PMID- 15475241
TI  - Differential domain evolution and complex RNA processing in a family of
      paralogous EPB41 (protein 4.1) genes facilitate expression of diverse tissue
      specific isoforms.
AB  - The EPB41 (protein 4.1) genes epitomize the resourcefulness of the mammalian
      genome to encode a complex proteome from a small number of genes. By utilizing
      alternative transcriptional promoters and tissue-specific alternative pre-mRNA
      splicing, EPB41, EPB41L2, EPB41L3, and EPB41L1 encode a diverse array of
      structural adapter proteins. Comparative genomic and transcript analysis of these
      140- to 240-kb genes indicates several unusual features: differential evolution
      of highly conserved exons encoding known functional domains interspersed with
      unique exons whose size and sequence variations contribute substantially to
      intergenic diversity; alternative first exons, most of which map far upstream of
      the coding regions; and complex tissue-specific alternative pre-mRNA splicing
      that facilitates synthesis of functionally different complements of 4.1 proteins
      in various cells. Understanding the splicing regulatory networks that control
      protein 4.1 expression will be critical to a full appreciation of the many roles
      of 4.1 proteins in normal cell biology and their proposed roles in human cancer.

PMID- 15475242
TI  - A NotI-EcoRV promoter library for studies of genetic and epigenetic alterations
      in mouse models of human malignancies.
AB  - Aberrant promoter methylation and associated chromatin changes are primarily
      studied in human malignancies. Thus far, mouse models for human cancer have been
      rarely utilized to study the role of DNA methylation in tumor onset and
      progression. It would be advantageous to use mouse tumor models to a greater
      extent to study the role and mechanism of DNA methylation in cancer because mouse
      models allow manipulation of the genome, study of samples/populations with a
      homogeneous genetic background, the possibility of modulating gene expression in
      vivo, the statistical power of using large numbers of tumor samples, access to
      various tumor stages, and the possibility of preclinical trials. Therefore, it is
      likely that the mouse will emerge as an increasingly utilized model to study DNA
      methylation in cancer. To foster the use of mouse models, we developed an arrayed
      mouse NotI-EcoRV genomic library, with clones from three commonly used mouse
      strains (129SvIMJ, FVB/NJ, and C57BL/6J). A total of 23,040 clones representing
      an estimated three- to fourfold coverage of the mouse genome were arrayed in 60 x
      384-well plates. We developed restriction landmark genomic scanning (RLGS) mixing
      gels with 32 plates to enable the cloning of methylated sequences from RLGS
      profiles run with NotI-EcoRV-HinfI. RLGS was used to study aberrant methylation
      in two mouse models that overexpressed IL-15 or c-Myc and developed either T/NK
      cell leukemia or T-cell lymphomas, respectively. Careful analysis of 198
      sequences showed that 188 (94.9%) identified CpG-island sequences, 132 sequences
      (66.7%) had homology to the 5' regions of known genes or mRNAs, and all 132 NotI
      EcoRV clones were located at the same CpG islands with the predicted promoter
      sequences. We have also developed a modified pGL3-based luciferase vector that
      now contains the NotI, AscI, and EcoRV restriction sites and allows the rapid
      cloning of NotI-EcoRV library fragments in both orientations. Luciferase assays
      using NotI-EcoRV clones confirmed that the library is enriched for promoter
      sequences. Thus, this library will support future genetic and epigenetic studies
      in mouse models.

PMID- 15475243
TI  - Pharmacogenomic assessment of carboxylesterases 1 and 2.
AB  - Human carboxylesterases 1 and 2 (CES1 and CES2) catalyze the hydrolysis of many
      exogenous compounds. Alterations in carboxylesterase sequences could lead to
      variability in both the inactivation of drugs and the activation of prodrugs. We
      resequenced CES1 and CES2 in multiple populations (n = 120) to identify single
      nucleotide polymorphisms and confirmed the novel SNPs in healthy European and
      African individuals (n = 190). Sixteen SNPs were found in CES1 (1 per 300 bp) and
      11 in CES2 (1 per 630 bp) in at least one population. Allele frequencies and
      estimated haplotype frequencies varied significantly between African and European
      populations. No association between SNPs in CES1 or CES2 was found with respect
      to RNA expression in normal colonic mucosa; however, an intronic SNP (IVS10-88)
      in CES2 was associated with reduced CES2 mRNA expression in colorectal tumors.
      Functional analysis of the novel polymorphisms described in this study is now
      warranted to identify putative roles in drug metabolism.

PMID- 15475244
TI  - Mapping of the BALB/c Ly49 cluster defines a minimal natural killer cell receptor
      gene repertoire.
AB  - The BALB/c inbred mouse strain is one of the most commonly used for immunological
      studies and is an animal model for natural killer (NK) cell function during
      pathogen infection and tumorigenesis. To understand better NK cell function in
      this strain, the complete BALB/c Ly49 haplotype was deduced. The BALB/c haplotype
      spans approximately 300 kb with a gene order and content of Ly49q, e, x, i, g, l,
      c, and a. Functional BALB/c alleles of Ly49q and e were isolated and found to be
      conserved. The BALB/c cluster represents a minimal haplotype as it contains many
      fewer functional genes than the 129 or B6 mouse strains. The small number of
      BALB/c Ly49 genes is due mainly to an absent group of genes (relative to B6 and
      129) between Ly49x and i, although other smaller deletions are present. These
      gene deletions provide a genetic basis for the lack of certain Ly49-associated NK
      cell functions in this mouse strain. Finally, the mapping of a third Ly49
      haplotype reveals that the basic murine Ly49 repertoire is composed of three
      framework gene pairs (Ly49q and e, Ly49i and g, and Ly49c and a) that are
      interspersed with variable numbers of strain-specific Ly49.

PMID- 15475245
TI  - The immunoglobulin lambda variable light-chain region in primates has been shaped
      by multiple, independent, small-scale and large-scale insertion/deletion events.
AB  - We analyzed genomes of nonhuman primates to determine the ancestral state of a
      9.1-kb insertion/deletion polymorphism, located on human chromosome 22. The 9.1
      kb+ allele was found in 16 chimpanzees, 3 bonobos, and 2 Bornean orangutans;
      however, 9 chimpanzees and 6 Sumatran orangutans showed neither the 9.1-kb+ nor
      the 9.1-kb- allele, but a novel allele, termed 9.1-kbnull. A clone from a
      chimpanzee BAC library carrying the 9.1-kbnull allele was sequenced: the BAC DNA
      aligns with the human chromosome 22 reference sequence except for a 75-kb region,
      suggesting that the 9.1-kbnull allele originated from a deletion. Furthermore,
      the 9.1-kb+ chromosomes of chimpanzees and bonobos contain a 1030-nucleotide
      sequence, absent in humans, that may result from a retro-transposition insertion
      in their common ancestor. Our results provide additional evidence that human
      chromosome 22 has undergone multiple small-scale and large-scale insertions and
      deletions since sharing a common ancestor with other primates.

PMID- 15475246
TI  - Silencing of the immunoglobulin heavy chain locus by removal of all eight
      constant-region genes in a 200-kb region.
AB  - Silencing or removal of individual C (constant)-region genes and/or adjacent
      control sequences did not generate fully deficient Ig (immunoglobulin)- mice. A
      reason is that different C genes share many functional tasks and most importantly
      are individually capable of ensuring lymphocyte differentiation. Nevertheless,
      incomplete arrests in B-cell development were found, most pronounced at the onset
      of H-chain expression. Here we show that removal of 200 kb accommodating all C
      genes, Cmu-Cdelta-Cgamma3-Cgamma1-Cgamma2b-Cgamma2a-Cepsilon-Calpha, stops
      antibody production. For this two loxP targeting constructs were introduced into
      the most 5' C gene and the distal alpha 3' enhancer. Cre-loxP-mediated in vivo
      deletion was accompanied by extensive germ-line mosaicism, which could be
      separated by breeding. Homozygous C-gene deletion mice did not express Ig H or L
      chains and flow cytometry revealed a complete block in B-cell development.
      However, C-gene removal did not affect DNA rearrangement processes following
      locus activation, as recombination efficacy appears to be similar to what is
      found in normal mice.

PMID- 15475247
TI  - High-resolution comparative mapping between human chromosomes 4 and 8 and bovine
      chromosome 27 provides genes and segments serving as positional candidates for
      udder health in cattle.
AB  - To get more information about the order of genes located in Bos taurus (BTA)
      chromosome 27 segments, supposed to harbor loci influencing clinical mastitis and
      somatic cell count, and to identify genes that serve as positional candidates for
      the mentioned traits, we constructed a high-resolution, comparative, and
      comprehensive gene map for BTA27. The map includes 57 loci in a 5000-rad cattle
      hamster whole genome radiation hybrid panel supported by 50 syntenic assignments
      in a cattle-murine somatic hybrid cell panel. Thirty-eight new loci (36 genes, 2
      microsatellites) together with repeated mappings of 5 genes and 7 microsatellites
      and integration of existing data from 7 microsatellites were used to generate a
      comprehensive RH5000 map. The RH map, constructed at lod score criterion 8 using
      the software RHMAP v.3.0, consisted of three linkage groups 23, 22, and 590
      cR5000 in length. Gene assignments on BTA27 and the localization of 8 more genes
      on BTA8 and BTA14 previously predicted on BTA8/BTA27 and BTA14/BTA27 narrowed
      down significantly the chromosome break points between the three cattle
      chromosomes and segments on Homo sapiens chromosomes HSA4 and HSA8. Defined
      evolutionary break points increase the accuracy of comparative in silico mapping
      of further human genes in conserved chromosome segments of BTA27.

PMID- 15475248
TI  - Characterization of a common deletion polymorphism of the UGT2B17 gene linked to
      UGT2B15.
AB  - Members of the human UDP-glucuronosyltransferase 2B family are located in a
      cluster on chromosome 4q13 and code for enzymes whose gene products are
      responsible for the normal catabolism of steroid hormones. Two members of this
      family, UGT2B15 and UGT2B17, share over 95% sequence identity. However, UGT2B17
      exhibits broader substrate specificity due to a single amino acid difference.
      Using gene-specific primers to explore the genomic organization of these two
      genes, it was determined that UGT2B17 is absent in some human DNA samples. The
      gene-specific primers demonstrated the presence or absence of a 150 kb genomic
      interval spanning the entire UGT2B17 gene, revealing that UGT2B17 is present in
      the human genome as a deletion polymorphism linked to UGT2B15. Furthermore, it is
      shown that the UGT2B17 deletion polymorphism shows Mendelian segregation and
      allele frequencies that differ between African Americans and Caucasians.

PMID- 15475249
TI  - An mRNA amplification procedure with directional cDNA cloning and strand-specific
      cRNA synthesis for comprehensive gene expression analysis.
AB  - We developed an integrated system suitable for comprehensive gene expression
      studies including construction and analysis of cDNA microarrays starting from a
      small amount of mRNA. We amplified total mRNA first as cDNA mixtures by
      polymerase chain reaction and then as strand-specific cRNA mixtures by in vitro
      transcription. These amplified cDNA and cRNA enabled determination of mRNA levels
      by hybridization analyses such as Southern, Northern, reverse-Northern
      macroarray, and cDNA microarray analyses, as well as construction of the cDNA
      library with a unidirectional cDNA insert. By using strand-specific cRNA derived
      from rat primary-cultured hepatocytes, we detected putative antisense transcripts
      for the metallothionein gene. cDNA microarray analysis for genes regulated by
      glucocorticoids and glucagon in the hepatocytes revealed that a number of genes
      involved in signal transduction and transcriptional regulation were up- or down
      regulated. The present system is widely applicable to gene expression analysis
      with limited amounts of RNA samples.

PMID- 15475251
TI  - Identification of the mouse H-ficolin gene as a pseudogene and orthology between
      mouse ficolins A/B and human L-/M-ficolins.
AB  - Ficolin is a collagenous lectin which plays a crucial role in innate immunity.
      Three and two ficolins have been identified in human and mice, respectively. To
      identify the mouse homologue of human H-ficolin and to elucidate the orthology
      between mouse ficolins A/B and human L-/M-ficolins, the gene structures were
      explored. The mouse homologue of the H-ficolin gene was identified as a
      pseudogene on chromosome 4. The mouse ficolin A gene was located far from the
      ficolin B gene on chromosome 2, whereas the human L-ficolin and M-ficolin genes
      were close in the region homologous to the ficolin B locus. Together with the
      exon-intron structures and the phylogenetic tree, these results suggest that
      ficolin B is the mouse orthologue of M-ficolin and that the genes encoding serum
      type ficolins, ficolin A and L-ficolin, were generated independently from the
      ficolin B/M-ficolin lineage each in mice and primates.

PMID- 15475250
TI  - Molecular cloning and characterization of canine ICOS.
AB  - Inducible costimulatory receptor (ICOS) is one recently identified member of the
      CD28 family of costimulatory molecules. Evidence suggests ICOS functions as a
      critical immune regulator and, to evaluate these effects, we employed the canine
      model system that has been used to develop strategies currently in clinical use
      for hematopoietic stem cell transplantation. To investigate the effects of
      blocking the ICOS pathway in the canine hematopoietic cell transplantation model,
      we tested existing murine and human reagents and cloned the full length of the
      open reading frame of canine ICOS cDNA to allow the development of reagents
      specific for the canine ICOS. Canine ICOS contains a major open reading frame of
      624 nucleotides, encoding a protein of 208 amino acids, and localizes to
      chromosome 37. Canine ICOS shares 79% sequence identity with human ICOS, 70% with
      mouse, and 69% with rat. Canine ICOS expression is limited to stimulated PBMC.

PMID- 15475252
TI  - Novel human testis-specific histone H2B encoded by the interrupted gene on the X
      chromosome.
AB  - Testis-specific histones are synthesized and accumulated at specific stages of
      mammalian spermatogenesis. Their proposed functions range from facilitation of
      the replacement of somatic histones by protamines to epigenetic control of gene
      transcription. Several testis histone variants were characterized in mouse and
      rat; however, few are known in humans. Here we report the identification and
      characterization of a novel human histone 2B gene (TH2B-175) located at Xq22.2,
      which encodes a highly divergent H2B variant. The TH2B-175 gene contains two
      introns and is transcribed exclusively in testis, where the spliced
      polyadenylated mRNA was detected. Genomic PCR, Southern blot analysis, and BLAST
      based searches indicate that TH2B-175 evolved in the primate lineage or has been
      lost in rodents. In transfected Chinese hamster cells, GFP-tagged TH2B-175
      targeted to large fluorescent bodies that partially colocalize with the
      interstitial telomeric blocks. Therefore, TH2B-175 may have telomere-associated
      functions and participate in the telomere-binding complex in the human sperm [1].

PMID- 15475253
TI  - Effects of chromosomal rearrangements on human-chimpanzee molecular evolution.
AB  - Many chromosomes are rearranged between humans and chimpanzees while others
      remain colinear. It was recently observed, based on over 100 genes, that the
      rates of protein evolution are substantially higher on rearranged than on
      colinear chromosomes during human-chimpanzee evolution. This finding led to the
      conclusion, since debated in the literature, that chromosomal rearrangements had
      played a key role in human-chimpanzee speciation. Here we re-examine this
      important conclusion by employing larger a data set (over 7000 genes), as well as
      alternative analyses. We show that the higher rates of protein evolution on
      rearranged chromosomes observed in the earlier study are not reproduced by our
      survey of the larger data set. We further show that the conclusion of the earlier
      study is likely confounded by two factors introduced by the relatively limited
      sample size: (1) nonuniform distribution of genes in the genome, and (2)
      stochastic noise in substitution rates inherent to short lineages such as the
      human-chimpanzee lineage. Our results offer a general cautionary note on the
      importance of controlling for hidden factors in studies involving bioinformatic
      surveys.

PMID- 15475254
TI  - Information for the Coordinates of Exons (ICE): a human splice sites database.
AB  - We present a comprehensive database, Information for the Coordinates of Exons
      (ICE), of genomic splice sites (SSs) for 10,803 human genes. ICE contains 91,846
      pairs of donor acceptor sites, supported by the alignment of "full-length" human
      mRNAs (including transcript variants) on human genomic sequences. ICE represents
      the largest collection of human SSs known to date and provides a significant
      resource to both molecular biologists and bioinformaticians alike. A user can
      visualize and extract genomic sequences around SSs of the donor acceptor pairs
      and can also visualize the primary structure of individual genes. We list in this
      article the 22 most frequently found canonical and noncanonical splice sites. The
      top four most represented donor acceptor pairs (GT-AG, GC-AG, AT-AC, and GT-GG)
      accounted for 99.16% of our data set. In addition, we calculated the SS matrix
      models for the three most common donor acceptor pairs. The database is focused on
      providing SSs and surrounding sequence information, associated SS and sequence
      characteristics, and relation to overall transcript structure. It allows targeted
      search and presents evidence for the gene structure.

PMID- 15475255
TI  - SUM: a new way to incorporate mismatch probe measurements.
AB  - Affymetrix's high-density oligonucleotide arrays offer an exciting technology in
      biomedical research. With more and more statistical involvement in every step of
      the process, there has been a constant effort to make sure that the expression
      data are appropriately extracted in the first place. According to Affymetrix
      GeneChip technology, each gene is represented by 11-20 oligo probe pairs; the
      challenge is how to extract one meaningful number, expression, from the 11-20
      pairs of numbers. More specifically, there is first a need to differentiate the
      components of specific binding, nonspecific binding, and optical background noise
      in both PM and MM probes, and then an expression measure that is proportional to
      the true abundance of transcripts is to be derived. A new method, SUM, which sums
      up PM and MM values and then follows a process similar to that of RMA, is
      considered. The performance of SUM is investigated and compared to the three most
      popular methods, MAS5, dChip, and RMA. The assessments are based on a well
      controlled experiment dataset that is publicly available. The results show that
      in several respects the performance of SUM is comparable to that of RMA and
      dChip, and all three of these methods show some advantages over MAS5. There is
      some evidence showing that SUM has higher differential sensitivity than other
      methods in certain situations.

PMID- 15475256
TI  - Genetic admixture of European FRDA genes is the cause of Friedreich ataxia in the
      Mexican population.
AB  - Friedreich ataxia accounts for approximately 75% of European recessive ataxia
      patients. Approximately 98% of pathogenic chromosomes have large expansions of a
      GAA triplet repeat in the FRDA gene (E alleles), and strong linkage
      disequilibrium among polymorphisms spanning the FRDA locus indicates a common
      origin for all European E alleles. In contrast, we found that only 14 of 151
      (9.3%) Mexican Mestizo patients with recessive ataxia were homozygous for E
      alleles. Analysis of polymorphisms spanning the FRDA locus revealed that all
      Mestizo E alleles had the common European haplotype, indicating that they share a
      single origin. Genetic admixture levels were determined, which revealed that the
      relative contributions to the Mestizo FRDA gene pool by Native American and
      European genes were 76-87% and 13-24%, respectively, commensurate with the
      observed low prevalence of Friedreich ataxia in Mestizos. This indicates that
      Friedreich ataxia in Mexican Mestizos is due to genetic admixture of European
      mutant FRDA genes in the Native American gene pool that existed prior to contact
      with Europeans.

PMID- 15475257
TI  - The influence of neighboring-nucleotide composition on single nucleotide
      polymorphisms (SNPs) in the mouse genome and its comparison with human SNPs.
AB  - We analyzed the neighboring-nucleotide composition of 433,192 biallelic
      substitutions, representing the largest public collection of SNPs across the
      mouse genome. Large neighboring-nucleotide biases relative to the genome- or
      chromosome-specific average were observed at the immediate adjacent sites and
      small biases extended farther from the substitution site. For all substitutions,
      the biases for A, C, G, and T were 0.21, 2.63, 0.71, and -3.55%, respectively, on
      the immediate adjacent 5' site and -3.67, 0.75, 2.69, and 0.23%, respectively, on
      the immediate adjacent 3' side. Further examination of the six categories of
      substitution revealed that the neighboring-nucleotide patterns for transitions
      were strongly influenced by the hypermutability of dinucleotide CpG and the
      neighboring effects on transversions were complex. Probability of a transversion
      increased with increasing A + T content of the two immediate adjacent sites,
      which was similarly observed in the human and Arabidopsis genomes. Overall, the
      bias patterns for the neighboring nucleotides in the mouse and human genomes were
      essentially the same; however, the extent of the biases was notably less in mice.
      Our results provide the first comprehensive view of the neighboring-nucleotide
      effects in the mouse genome and are important for understanding the mutational
      mechanisms and sequence evolution in the mammalian genomes.

PMID- 15475258
TI  - Amplicons on human chromosome 11q are located in the early/late-switch regions of
      replication timing.
AB  - Amplicons are frequently found in human tumor genomes, but the mechanism of their
      generation is still poorly understood. We previously measured the replication
      timing of the genes along the entire length of human chromosomes 11q and 21q and
      found that many "disease-related" genes are located in timing-transition regions.
      In this study, further scrutiny of the updated replication-timing map of human
      chromosome 11q revealed that both amplicons on human chromosomal bands 11q13 and
      11q22 are located in the early/late-switch regions of replication timing in two
      human cell lines (THP-1 and Jurkat). Moreover, examination of synteny in the
      human and mouse genomes revealed that synteny breakage in both genomes occurred
      primarily at the early/late-switch regions of replication timing that we had
      identified. In conclusion, we found that the early/late-switch regions of
      replication timing coincided with "unstable" regions of the genome.

PMID- 15475259
TI  - Evidence for turnover of functional noncoding DNA in mammalian genome evolution.
AB  - The vast majority of the mammalian genome does not code for proteins, and a
      fundamental question in genomics is: What proportion of the noncoding mammalian
      genome is functional? Most attempts to address this issue use sequence
      comparisons between highly diverged mammals such as human and mouse to identify
      conservation due to negative selection. But such comparisons will underestimate
      the true proportion of functional noncoding DNA if there is turnover, if patterns
      of negative selection change over time. Here we test whether the inferred level
      of negative selection differs between different pairwise species comparisons.
      Using a multiple alignment of more than a megabase of contiguous sequence from
      eight mammalian species, we find a strong negative relationship between inferred
      levels of negative selection and pairwise divergence using 21 pairwise
      comparisons. This result suggests that there is a high rate of turnover of
      functional noncoding elements in the mammalian genome, so measures of functional
      constraint based on human-mouse comparisons may seriously underestimate the true
      value.

PMID- 15475260
TI  - Comparative sequence analysis of the Gdf6 locus reveals a duplicon-mediated
      chromosomal rearrangement in rodents and rapidly diverging coding and regulatory
      sequences.
AB  - Duplicated segments of genomic DNA can catalyze both gene evolution and
      chromosome evolution. Here we describe a rodent-specific duplication involving
      the Uqcrb gene, a cis-regulatory element for the Gdf6 gene, and a chromosomal
      rearrangement. Comparisons of Gdf6 sequences from several placental mammals and
      platypus revealed many strongly conserved regions flanking Gdf6 and the adjacent
      Uqcrb gene. However, in rat and mouse a synteny break resides approximately 70 kb
      upstream of Gdf6, such that Gdf6 and Uqcrb are on separate chromosomes. In
      rodents, Gdf6 and Uqcrb are both associated with homologous duplicons that may
      have catalyzed a rearrangement separating the two genes. However, the duplicon
      spanned both Uqcrb and a cis-regulatory element that controls Gdf6 transcription
      in limb skeletal joints. In mouse and rat, one duplicon now contains a degrading
      Uqcrb pseudogene but retains strongly conserved sequences within a Gdf6 enhancer.
      In contrast, the other duplicon has retained the intact Uqcrb gene and (in mouse)
      a copy of the Gdf6 enhancer that has acquired novel mutations. The duplicons have
      separately maintained distinct functions of the ancestral sequence, consistent
      with a "subfunction partitioning" evolutionary model. These findings also provide
      an example of a duplication that mobilized a tissue-specific enhancer from its
      cognate gene, and new evidence that duplications can be associated with
      chromosomal rearrangements. Furthermore, these data suggest that segmental
      duplications could lead to evolution of novel gene expression patterns via
      diversification of regulatory elements.

PMID- 15475261
TI  - The dominant alopecia phenotypes Bareskin, Rex-denuded, and Reduced Coat 2 are
      caused by mutations in gasdermin 3.
AB  - Reduced Coat 2 (Rco2) is an ENU-induced mutation affecting hair follicle
      morphogenesis by an abnormal and protracted catagen. We describe chromosomal
      mapping and molecular identification of the autosomal dominant Rco2 mutation. The
      Rco2 critical region on mouse chromosome 11 encompasses the alopecia loci,
      Bareskin (Bsk), Rex-denuded (Re(den)), Recombination induced mutation 3 (Rim3),
      and Defolliculated (Dfl). Recently, the gasdermin (Gsdm) gene was described as
      predominantly expressed in skin and gastric tissues. We provide evidence for a
      murine-specific gene cluster consisting of Gsdm and two closely related genes
      which we designate as Gsdm2 and Gsdm3. We show that Gsdm3 reflects a mutation
      hotspot and that Gsdm3 mutations cause alopecia in Rco2, Re(den), and Bsk mice.
      We infer a role of Gsdm3 during the catagen to telogen transition at the end of
      hair follicle morphogenesis and the formation of hair follicle-associated
      sebaceous glands.

PMID- 15475262
TI  - Intraspecific mating with CzechII/Ei mice rescue lethality associated with loss
      of function mutations of the imprinted genes, Igf2r and Cdkn1c.
AB  - Maternal inheritance of targeted loss of function alleles encoding either the
      cyclin-dependent kinase inhibitor 1C (Cdkn1c) or the insulin-like growth factor 2
      receptor (Igf2r) leads to fully penetrant perinatal lethality in C57BL/6J mice
      due to genomic imprinting. Here, we demonstrate that there is a marked
      enhancement in postnatal viability of F(1) mice carrying either the ablated Igf2r
      ( approximately 32%) or Cdkn1c ( approximately 83%) when the paternal genome was
      derived from the inbred Mus musculus musculus CzechII/Ei strain. Genetic and
      molecular analyses indicated that the increased viability was not caused by
      relaxation of imprinted gene expression, but is the consequence of unidentified
      polygenic modifiers that are not imprinted. In the course of this study,
      restriction-site polymorphisms between 129S1 and CzechII/Ei in 21 imprinted and
      14 biallelically expressed genes were identified. These polymorphisms may prove
      useful in determining the effects of different mutant backgrounds on genomic
      imprinting.

PMID- 15475263
TI  - Analysis of reciprocal congenic lines reveals the C3H/HeJ genome to be highly
      resistant to ApcMin intestinal tumorigenesis.
AB  - Genetic background affects polyp development in the Multiple intestinal neoplasia
      (Apc(Min)) mouse model. The Modifier of Min 1 (Mom1) locus accounts for
      approximately 50% of the variation in polyp multiplicity. We generated reciprocal
      congenic lines, such that the recipient C57BL/6J (B6) strain carries a donor
      C3H/HeJ (C3H) Mom1 allele, and the recipient C3H strain carries a donor B6 Mom1
      allele. Hybrid progeny from congenic females mated to B6 Apc(Min/+) males were
      analyzed. A single C3H Mom1 locus on the B6 background reduced small intestinal
      polyp numbers by 50% and colon polyp incidence by 66% compared to their
      susceptible B6 Mom1(S/S)Apc(Min/+) siblings. These findings show that the C3H
      genome contains a resistant Mom1(R) locus. The reciprocal congenic line, which
      carries the susceptible B6 Mom1(S) locus on the C3H background, reduced small
      intestinal polyp numbers by 80% and colon polyp incidence by 95% compared to B6
      Mom1(S/S)Apc(Min/+) mice. These data demonstrate that unidentified modifiers in
      the C3H strain can suppress intestinal polyp multiplicity in Apc(Min/+) mice, and
      act in the absence of a resistant Mom1(R) locus.

PMID- 15475265
TI  - Hash4, a novel human achaete-scute homologue found in fetal skin.
AB  - To find additional members of the basic helix-loop-helix (bHLH) protein family in
      human, the bioinformatic tools provided by the National Center for Biotechnology
      Information was used for homology searches through databases. We report the
      identification and cloning of a new, fourth member in the achaete-scute complex
      family of genes, Hash4 or Ascl4, which maps to chromosome 12q24.1. The bHLH
      domain of the putative HASH4 protein shows most identity to HASH3/ASCL3. The
      expression of Hash4 and Hash3 was analyzed by reverse transcriptase polymerase
      chain reaction (PCR), in a panel of different human tissues and cells. Expression
      of Hash3 was detected in all samples tested, while the expression of Hash4 was
      restricted to skin. Quantification of the Hash4 expression by real-time PCR
      revealed a 7-fold higher expression in fetal skin compared to adult skin. Our
      results suggest HASH4 to be involved in skin development.

PMID- 15475264
TI  - Genetic mapping of a Ptch1-associated rhabdomyosarcoma susceptibility locus on
      mouse chromosome 2.
AB  - Mutations in the Patched (Ptch1) gene are responsible for various familial and
      sporadic cancers. Ptch1(neo67/+) mice, in which exons 6 and 7 are deleted, show
      genetic background-dependent susceptibility to the development of muscle tumors
      resembling human rhabdomyosarcoma (RMS); BALB/c (BALB) is a susceptible strain
      whereas C57BL/6 (B6) shows resistance. A genome-wide linkage analysis was carried
      out using Ptch1(neo67/+)mice produced from B6 x (BALB x B6) backcrosses to
      identify loci involved in the control of RMS susceptibility. Quantitative trait
      locus mapping with the censored tumor latency time as the quantitative parameter
      was used to detect a significant RMS susceptibility modifier locus, Parms1
      (Patched-Associated RMS 1), on chromosome 2 between D2Mit37 and D2Mit102 (LRS =
      10). A Kaplan-Meier survival curve revealed that mice with the B6/BALB genotype
      develop tumors more frequently and much faster as compared to mice homozygous for
      the B6 allele (P = 0.02). Additional loci not reaching linkage significance were
      also detected for medulloblastoma resistance.

PMID- 15475266
TI  - Genome-wide transcriptome mapping analysis identifies organ-specific gene
      expression patterns along human chromosomes.
AB  - The Human Genome Project has revealed that there about 32,000 protein-encoding
      genes, which are distributed throughout the genome. It is unclear, however,
      whether genes are distributed on the chromosomes according to patterns linked to
      organ specificity. To explore the relationship between genes actively transcribed
      in normal tissues and their chromosomal locations, we analyzed serial analysis of
      gene expression libraries of normal human liver, brain, breast, and colon
      tissues. Transcriptome mapping analysis revealed that transcriptional activity in
      each tissue varied according to the chromosomal domains, and a weak positive
      correlation was observed between transcription density and gene density. We
      identified six liver-related and five colon-related chromosomal domains highly
      transcribed in each tissue, whereas no brain-related or breast-related
      chromosomal domains were identified. Representative genes located on these
      chromosomal domains were associated with the function of each organ and were
      highly conserved in both mouse and rat genomes. These data revealed that the
      transcriptional activities of normal human tissues are well orchestrated at
      chromosomal levels, suggesting that highly expressed genes may share physical
      proximity.

PMID- 15475267
TI  - Gene discovery by microarray: identification of novel genes induced during growth
      factor-mediated muscle cell survival and differentiation.
AB  - Peptide growth factors regulate cell fate by activating distinct signal
      transduction pathways that ultimately influence gene expression. Insulin-like
      growth factors (IGFs) play central roles in controlling somatic growth and
      participate in skeletal muscle development and regeneration. In cultured muscle
      cells, IGF action is critical both for maintaining viability during the
      transition from proliferating to differentiating myoblasts and for facilitating
      differentiation. By contrast, platelet-derived growth factor (PDGF) can sustain
      cell survival but inhibits differentiation. Here we examine the genetic programs
      that accompany IGF and PDGF action in myoblasts. Through analysis of high-density
      oligonucleotide arrays containing approximately 36,000 mouse probe sets, we
      identify 90 transcripts differentially induced by IGF-I, including 28 muscle
      specific genes and 33 previously unannotated mRNAs, and 55 transcripts
      specifically stimulated by PDGF, including 14 unknowns. Detailed study of one IGF
      induced mRNA shows that it encodes a protein related to a recently characterized
      repulsive guidance molecule postulated to regulate neuronal targeting during
      development. Our results demonstrate the power of transcriptional profiling for
      gene discovery and provide opportunities for investigating new proteins
      potentially involved in different aspects of growth factor action in muscle.

PMID- 15475269
TI  - [Up to 18 years of age].

PMID- 15475268
TI  - Interpreting mammalian evolution using Fugu genome comparisons.
AB  - Recently, it has been shown that a significant number of evolutionarily conserved
      human-Fugu noncoding elements function as tissue-specific transcriptional
      enhancers in vivo, suggesting that distant comparisons are capable of identifying
      a particular class of regulatory elements. We therefore hypothesized that by
      juxtaposing human/Fugu and human/mouse conservation patterns we can define
      conservation criteria for discovering transcriptional regulatory elements
      specific to mammals. Genome-scale comparisons of noncoding human/Fugu
      evolutionary conserved elements (ECRs) and their humans/mouse counterparts
      revealed a particular signature common to human/mouse ECRs (>or=350 bp long,
      >or=77% identity) that are also conserved in fishes. This newly defined threshold
      identifies 90% of all human/Fugu noncoding ECRs without the assistance of human
      Fugu genome alignments and provides a very efficient filter for identifying
      functional human/mouse ECRs.

PMID- 15475270
TI  - [Predicting the use of Emla cream by the triage nurse in a paediatric emergency
      department].
AB  - INTRODUCTION: The current issue of paediatric emergency care is to decrease the
      length of stay of the child and his/her family in the emergency department while
      improving health care quality. Up to now, the paediatric emergency department's
      triage nurses of the children's Timone hospital apply two EMLA patches when they
      think that a blood test will be ordered by the medical doctor in order to
      decrease the waiting time between the clinical exam and the blood test. PURPOSE:
      The objective of this study was to check if this attitude allowed to efficiently
      select children who will actually get a blood test. MATERIAL AND METHODS: During
      four weeks, the triage nurses were asked to write down for each patient after the
      reception time whether or not a blood test would be ordered by the medical doctor
      after clinical exam. We compared these data to the number of blood tests actually
      done. RESULTS: Out of the 2758 children admitted in the emergency department
      during this period, 1973 nurse prediction forms were filled out. The triage
      nurses predicted a blood test for 253 patients. Out of these 253 patients, only
      132 of them had a blood test done. The study of various studied criteria did not
      allow to reveal any good agreement between the nurse and the medical doctor.
      CONCLUSION: The literature study shows that some medical criteria allow to
      improve this agreement rate. The assessment of blood test necessity have to be
      carried on and needs further studies in order to precise the most discriminant
      medical criteria.

PMID- 15475271
TI  - [Enuresis in children with sickle cell disease].
AB  - POPULATIONS AND METHODS: In order to analyze epidemiological and clinical
      characteristics of enuresis in children with sickle cell disease, and identify
      risk and aetiological factors, 987 subjects (aged 5-20 years) took part in a
      cross-sectional study. These children were divided into two groups: group 1
      consisted of 456 homozygous children with sickle cell disease (haemoglobin SS),
      while group 2 consisted of 531 normal children. These groups were paired
      according to age and sex. RESULTS: The prevalence of enuresis was 50.9% in group
      1 and 16.4% in group 2, and was significantly higher (P < 0.05) in the girls. The
      frequency decreased significantly between the ages of 5-20. At age 16, frequency
      of enuretic children with sickle cell disease remained statistically greater
      (15.9% vs. 8.0%). The frequency of wet nights was higher (P < 0.05) in group 1.
      In addition, anaemia crisis and painful crisis were related to prevalence of
      enuresis. There was a significant (P < 0.01) negative correlation between
      haemoglobin F percentage and prevalence of enuresis. CONCLUSION: Enuresis is
      frequent in children with sickle cell disease and its intensity is linked to
      severity of disease.

PMID- 15475272
TI  - [Drug administration to paediatric inpatient].
AB  - OBJECTIVE: Available commercial drugs in France are often unsuitable for
      children. The aim of this study was, for every medicinal form orally or
      parenterally administered, to identify and to quantify difficulties met by the
      nurses administering drugs to paediatric inpatients and to propose solutions to
      main identified problems. MATERIAL AND METHOD: The study was realized in 14
      hospitals by direct observation. The observer, provided with a questionnaire,
      followed during a time slot of at least 2 h for one or several nurses and raised
      all the oral or injectable administrations. RESULTS: One thousand and nine
      hundred forty-six observations were performed. The children were 12.6 +/- 17
      months old, and weighed 8.5 +/- 9.4 kg. Injectable drugs: half of the
      observations showed a posology and a mode of dilution not corresponding to the
      summary of product characteristics. Eight percent of orally administered drugs
      were injectable drugs. In 35.5% of cases, administered amount was lower than the
      quarter of the present quantity in the therapeutic unity. The rest of the
      therapeutic unity was thrown (77.2% of cases). Liquid oral forms: liquid oral
      forms were ready for use regarding 83.8% of cases. The medicine was
      readministered to the same patient (23.5%), and/or administered to other patients
      (80.0%). Capsules: 66.9% of the administered capsules were prepared by the
      hospital pharmacies. The pharmacies organized with an unit dose drug dispensing
      system produced significantly more preparations than those working by global
      distribution (P < 0.0001). In 58.4% of cases, the administered capsule was an off
      label drug. Tablets: 46% of drug administration concerned a tablet without
      pediatric indication. 46.7% of tablets were cut, 74% were crushed. Bags: in 35.2%
      of observations, the bag was not administered in its entirety. CONCLUSION: Our
      study confirms the unsuitability of drugs to paediatric inpatients, the necessity
      of recommendations of good practices in the administration of drugs to paediatric
      inpatients, and proposes corrective actions.

PMID- 15475273
TI  - [Outcome evaluation of education in asthmatic children: the Robert-Debre
      hospital's experience].
AB  - INTRODUCTION: Asthma, the most frequent chronic disease in childhood, is often
      treated by a continuous preventive treatment associated to the treatment of
      attacks. This therapeutic scheme fits well with educative skills. The Robert
      Debre's asthma school has been created in December 1999. Two nurses specialized
      in child asthma education are working in the school, helped by the pediatric
      pulmonologists. Children 6-year-old or more, that are treated in the hospital for
      asthma may be sent to the asthma school for education. They receive individual or
      collective education for cognitive, psycho-affective and sensory-motor targets
      related to asthma. AIM OF THE STUDY: To evaluate the outcome of educative action
      in childhood asthma and to study hospitalizations costs. METHODS:  SUBJECTS:
      children who received education for the first time in the year 2000 or 2001 and
      in whom exhaustive computerized data were available were eligible for the study.
      METHODS: retrospective and comparative study one-year-before/one-year-after the
      first educational intervention, assessed by comparison of the numbers of
      scheduled medical consultations and hospitalizations (and their cost). RESULTS:
      Sixty-six children were studied. We registered a significant increase of
      scheduled medical consultations (177 vs. 223; P < 0.03), and a very significant
      decrease of hospitalizations for asthma attacks (32 vs. 11; P < 0.001) without
      influence of the number of educational interventions and with a 52% decrease in
      costs (84,788 vs. 40,073 euros; P < 0.03). CONCLUSION: Asthmatic children
      education is a useful tool to improve medical follow-up and to decrease
      hospitalizations number. In a two-year survey, the decrease of cost in a group of
      66 children is 44,715 euros.

PMID- 15475274
TI  - [Paediatricians involvement in paediatric emergency care. A study in hospitals
      and paediatricians offices in the North of France].
AB  - Paediatrician involvement in paediatric emergency care is often considered
      insufficient. OBJECTIVES: To assess paediatrician involvement in paediatric
      emergency care, and how paediatric emergencies were dealt with in emergency
      department, paediatric emergency department, paediatric department and
      paediatrician offices. METHODS: Prospective multicentric study, January 29th,
      2001, including all the emergency visits of children admitted to an emergency
      department, paediatric emergency department, paediatric department or in
      paediatrician offices. RESULTS: Paediatricians examined an average number of 21
      children, 58% were considered as "urgent" (mean: 53% +/- 25% by paediatrician).
      Thirty five percent of paediatricians were available on call that night. In the
      18 hospitals, 705 children were admitted that day, 42% to an emergency
      department, 40% to a paediatric emergency department, 18% to a paediatric
      department. The mean age was 6 years +/- 5 years. Trauma represented 40% of all
      cases and was more frequent in emergency department than in paediatric emergency
      department or paediatric department (63% versus 33% and 2%, p < 10(-8)).
      Hospitalisation rate was lower in paediatric emergency department than in
      emergency department and paediatric department, especially for non-traumatic
      conditions. CONCLUSION: Our findings prove paediatrician involvement in
      paediatric emergency care, in paediatrician offices and in hospital. This study
      points out the complementarity and insufficiencies of these different services.

PMID- 15475275
TI  - [Risks and benefits of cardiac surgery in Down's syndrome with congenital heart
      disease].
AB  - Down's syndrome is the most frequent chromosomic anomaly. Fifty percent are
      associated with a congenital heart disease. Life expectancy and quality of life
      are increasing since 15 years with improving surgical techniques. PATIENTS AND
      METHODS: This study presents 73 patients with Down's syndrome who underwent a
      surgical repair of congenital heart disease between 1992 and 2002. Among them, 37
      (50.6%) had a complete atrio-ventricular septal defect (AVSD) and 36 an other
      anomaly. RESULTS: Five children died in the post operative period: all had an
      AVSD. Two late deaths occurred due to extra cardiac causes during the follow up.
      Two children who underwent a repair of AVSD had to be reoperated. The majority of
      the children are doing well, without any cardiac symptom. Thirty-eight percent of
      patients with AVSD repair have a middle mitral or tricuspid regurgitation and
      three had a massive mitral or tricuspid regurgitation. One child presents
      neurological sequelae related to surgery. CONCLUSION: Congenital heart diseases
      in Down's syndrome can be repaired with a limited risk of death. Final results
      are good for many children with significant improvement of the quality of life
      and life expectancy.

PMID- 15475276
TI  - [Hepatitis A infection and Henoch-Schonlein purpura: a rare association].
AB  - OBSERVATION: A 10-year-old boy presented cholestatic hepatitis A virus infection
      confirmed by IGM anti-HAV antibody. Three days after admission, he presented a
      palpable purpuric rash on the declivous regions, arthralgia and abdominal pain.
      He met all criteria set by the American College of Rheumatology (ACR) for Henoch
      Schonlein purpura. The evolution was gradually favorable with no renal
      involvement (recoil of 3 years and half). CONCLUSION: Henoch Schonlein purpura is
      an exceptional extra-hepatic manifestation of hepatitis A infection.

PMID- 15475278
TI  - [Sudden sight impairment revealing a cat-scratch disease: report of three cases].
AB  - Cat-scratch disease is a frequent but innocuous cause of chronic lymphadenopathy
      in children. Numerous atypical forms have been described. We report three cases
      of acute sight impairment revealing a cat-scratch disease. BACKGROUND: A 13 year
      old boy and two girls aged 10 and 13 suffered from a sudden bilateral sight
      impairment with papillary edema, with fever in two cases. Neurological
      examinations, X-rays and lumbar puncture results were found normal. However, all
      patients were tested positive to Bartonella Henselae. Antibiotic and anti
      inflammatory treatments were efficient in two cases. CONCLUSION: Cat-scratch
      disease can be characterized by an isolated and acute sight impairment with a
      stellate neuroretinitis. The potency of antibiotic treatments is debatable.

PMID- 15475277
TI  - [Extensive Hirschsprung's disease associated with intestinal malrotation].
AB  - Hirschsprung's disease (HD) involves the entire colon in less than 5% of cases,
      and the association of extensive HD with intestinal malrotation is very rare.
      This association of symptoms may delay both diagnosis and treatment. An infant
      presented with an intermittent occlusive syndrome that began neonatally.
      Intestinal malrotation was diagnosed radiologically, and treated surgically when
      the child was 2 months old. However, a chronic occlusion persisted. Biopsies of
      the rectum and the appendix demonstrated an absence of neurons in intestinal
      plexi. When the child was 17 months old, ileostomy and surgical excision of the
      segment affected by HD (the colon and terminal ileum) were performed. An ileoanal
      anastomosis was performed at the age of 29 months, with favorable outcome. The
      persistence of symptoms of intestinal occlusion after attempted treatment of
      intestinal malrotation must therefore suggest the possibility of associated HD in
      a young child.

PMID- 15475279
TI  - [Genetics of specific language impairments].
AB  - Specific language impairment (SLI), involving environmental as well as genetic
      factors, is a complex disorder affecting 5-10% of preschool-age children. This
      review summarizes current data regarding the genetic factors involved in SLI.
      Genetic factors were first implicated in SLI on the basis of twin studies and
      reports of familial cases. Furthermore, several studies have shown that the
      relative risk of SLI was higher for close relatives of affected individuals.
      Finally, a specific gene (FOXP2) has been identified on the long arm of
      chromosome 7 in a family affected with SLI, and several regions of the genome,
      i.e. 7q31, 16q and 19q, have been found to be strongly linked to SLI.

PMID- 15475280
TI  - [Treatment of status epilepticus in children with epilepsy].
AB  - The treatment of status epilepticus (SE) in children with epilepsy depends on the
      epilepsy syndrome, in order to avoid worsening drugs such as IV barbiturates in
      severe myoclonic epilepsy in infancy (SMEI) (Dravet's syndrome) or IV
      benzodiazepam in tonic SE of Lennox-Gastaut syndrome. Intensive care procedures
      should not be systematical in convulsive SE (CSE) and are not indicated in non
      convulsive SE (NCSE). Generalized CSE mostly involve SMEI before 3 years of age,
      symptomatic generalized epilepsy and partial lesional epilepsy. Treatment is an
      emergency and relies on IV benzodiazepines and, if necessary, IV phenytoine using
      plasmatic concentrations for an optimal management. The partial CSE of partial
      lesional epilepsy can result in focal deficit and need the same treatment as
      generalized CSE. NCSE consist in absence and/or myoclonic SE and are often
      unrecognised during a long time until EEG is performed. They mostly involve
      myoclonic epilepsies and can be controlled by IV benzodiazepines. The frequency
      of partial NCSE is underestimated, particularly in infants. Diagnosis relies on
      video EEG and treatment is the same as that used in partial CSE.

PMID- 15475281
TI  - [Role of implicit theories in primary school].
AB  - Since the 50s, the role of implicit theories in the organization and
      interpretation of information has gained increasing acceptance among both
      cognitive and social psychologists. These implicit theories refer to the two
      different assumptions people may make about the malleability of personal
      attributes. They may believe that a highly valued personal attribute, such as
      intelligence or morality, is fixed, i.e. a nonmalleable trait-like entity (entity
      theory), or that the attribute is a malleable quality that can be changed and
      developed (incremental theory). The identification of these two theories allows
      us to understand the cognition, emotion and behavior of individuals in
      achievement situations. Many studies carried out in the primary school show that
      children who hold an entity theory of personal attribute (i.e. they consider
      badness like a stable quality) have a strong tendency to attribute their failures
      to a fixed trait. They are more likely to attribute failures to their bad
      abilities. In contrast, children who hold an incremental theory of personal
      attribute (i.e. they consider badness as a malleable quality) are more likely to
      understand the same negative outcomes in terms of specific factors: they
      attribute them to a lack of effort. In addition, several studies have shown that
      entity theorists are more likely than incremental theorists to react helplessly
      in the face of failure. They are more likely to show negative affect and
      behaviors. This helpless response pattern is characterized by a lack of
      persistence. In contrast, incremental theorists try harder and develop better
      strategies and continue to work. Finally, several studies demonstrate that
      environmental factors play an important role in the implicit theories
      elaboration.

PMID- 15475283
TI  - [Non surgical replacement of the pulmonary valve: from experimental research to
      human application].

PMID- 15475284
TI  - [Parental antecedents of language problems and language evaluation in five and
      six-year-old children].

PMID- 15475285
TI  - [Nutritional status of 7-16 year-old children in Brazzaville: a 40 year-study
      (1963-2003)].

PMID- 15475286
TI  - [Castleman disease in a child].

PMID- 15475287
TI  - [Breastfeeding of infants].

PMID- 15475289
TI  - [Isolated brain stem dysfunction in a sibship].

PMID- 15475290
TI  - [Ocular traumatology in the infant].

PMID- 15475291
TI  - [Practical attitude toward arrhythmia in the neonate and infant].
AB  - Arrhythmias in neonates and infants require a specific management due to the
      particular nature of the rhythm anomalies in children. Accurate diagnosis of the
      tachycardia is realised mainly by means of ECG recording and vagal manoeuvres.
      The nature of the tachycardia will determine management, therapy and prognosis.
      In neonates <3 months, supraventricular tachycardia due to Wolff-Parkinson-White
      syndrome represents 70% of all supraventricular tachycardias, which, after
      conversion by vagal manoeuvres, requires a preventive treatment by digoxine (10
      y/kg/day tid). Neonatal flutter occurs in infants without structural heart
      disease. It has an excellent prognosis after conversion to sinus rhythm by
      transoesophageal pacing. Atrial tachycardia is less frequent but can induce a
      tachymyocardiopathy and often requires combined therapy including amiodarone.
      Long QT syndrome, clinically and genetically heterogeneous, is characterized by a
      prolongation of the QT interval (QTc > 440 ms) and a high risk of syncope and
      sudden death due to malignant ventricular arrhythmias. Beta-blockers
      significantly decrease cardiac events during follow-up. Congenital atrio
      ventricular block is rare but potentially lethal in the first months of life in
      the absence of permanent pacing. The morbidity remains high during long term
      follow-up in unpaced children.

PMID- 15475292
TI  - [Adolescent obesity: guidelines for the management].
AB  - The increasing prevalence of adolescent obesity justifies widespread effort and
      attention of the paediatrician. In order to manage, following points are to be
      documented: (I) weight status assessed on the basis of body mass index (BMI)split
      in two levels: obesity grade I: >or=97 eme centile, obesity grade 2: level IOTFC
      30; (2) complete anamnesis including age at adiposity rebound and existence of
      overweight in family; (3) research of associated morbidity and medical risks;(4)
      assessment of food intake and feeding practice; (5) assessment of physical
      activity; (6) talk with the adolescent to assess the psychological status,
      looking after depressive symptoms, anxiety, loss of self esteem. Once the items
      are documented, it allowed making a plan to manage the obesity in alliance with
      the adolescent and his family.

PMID- 15475293
TI  - [Antibiotic therapy for lower tract infections in children].
AB  - Lower respiratory tract infections in children encompass mainly bronchiolitis and
      community acquired pneumonia. Severity of bronchiolitis is linked to the
      intensity of the respiratory distress and young age. This syndrome is caused by
      viral infection, thus, initial antibiotherapy is not justified. In community
      acquired pneumonia, prognostic is dependent on the nature of the infective agent.
      Eventhough viruses are mainly responsible for the illness, bacterial (and
      particularly pneumococcal) agent cannot be ignored. Initial antibiotics must be
      efficient on Streptococcus pneumoniae.

PMID- 15475294
TI  - [Fauna, climate and politics: possible causes for the recent increases in tick
      borne zoonoses].

PMID- 15475295
TI  - [Radiological case study].

PMID- 15475296
TI  - Immune activation of apolipophorin-III and its distribution in hemocyte from
      Hyphantria cunea.
AB  - Apolipophorin-III (apoLp-III) is a hemolymph protein whose function is to
      facilitate lipid transport in an aqueous medium. Recently, apoLp-III in Galleria
      mellonella larvae was shown to play an unexpected role in insect immune
      activation. We identified the cDNA sequence of Hyphantria cunea apoLp-III by
      oligonucleotide-primed amplification, and 5'- and 3'-RACE PCR. Since H. cunea has
      an unusually low level of apoLp-III in the hemolymph, a recombinant apoLp-III was
      overexpressed using a baculovirus expression system to investigate its biological
      activity. Recombinant apoLp-III and/or Escherichia coli were injected into the
      hemocoel of last instar larvae, and the expression of antimicrobial peptide from
      fat body was determined by Northern blot. Injection of apoLp-III as well as E.
      coli induced slight up-regulation of its transcription rate in fat body, whereas
      the expression of antimicrobial peptide was dramatically induced by the injection
      of apoLp-III and E. coli. H. cunea hemocytes had apoLp-III in the granules and
      expressed its transcript, albeit at a much lower level than in the fat body. Upon
      bacterial injection, a subpopulation of hemocytes showed degranulation and
      degradation. Local discharge of apoLp-III from hemocytes caused by the injection
      of E. coli might be related to the immune response through an unknown mechanism.

PMID- 15475297
TI  - graal: a Drosophila gene coding for several mosaic serine proteases.
AB  - Serine proteases play vital roles in several biological processes such as
      development and immunity. We have characterized Graal, a large multi-domain
      serine protease from Drosophila. Graal is spliced in at least three transcripts
      that are present throughout development. The domains found in Graal proteins are:
      chitin-binding domains (CBD), scavenger receptor cysteine-rich (SRCR) domains,
      low density lipoprotein receptor cysteine-rich (LDLR-CR) domains, histidine and
      proline-rich domains, a NGGYQPP-repeat domain and a serine protease domain. The
      last 2370 nucleotides of these RNAs are identical and encode a His-rich domain,
      two SRCR domains, two LDLR-CR domains and a protease domain. The transcription of
      graal is upregulated after fungal or bacterial infection. Analysis of the Iso1
      (y;cn,sp,bw) strain shows that graal transcription is impaired in this fly line
      due to the insertion of a retrotransposon in the sixth exon. However, no
      phenotype could be observed consecutive to the absence of graal full length
      transcripts, particularly in the context of an immune challenge.

PMID- 15475298
TI  - Cloning, expression and functional characterisation of chitinase from larvae of
      tomato moth (Lacanobia oleracea): a demonstration of the insecticidal activity of
      insect chitinase.
AB  - Chitinases are vital to moulting in insects, and may also affect gut physiology
      through their involvement in peritrophic membrane turnover. A cDNA encoding
      chitinase was cloned from larvae of tomato moth (Lacanobia oleracea), a
      Lepidopteran pest of crops. The predicted protein contains 553 amino acid
      residues, with a signal peptide of 20 a.a. Sequence comparison showed 75-80%
      identity with other Lepidopteran chitinases. L. oleracea chitinase was produced
      as a functional recombinant enzyme in the yeast Pichia pastoris. A fusion protein
      containing chitinase joined to the N-terminus of snowdrop lectin (GNA) was also
      produced, to determine whether GNA could deliver chitinase to the haemolymph of
      Lepidopteran larvae after oral ingestion. The purified recombinant proteins
      exhibited similar levels of chitinase activity in vitro. Both proteins were
      highly toxic to L. oleracea larvae on injection, causing 100% mortality at low
      dose (2.5 microg/g insect). Injection of chitinase prior to the moult resulted in
      decreased cuticle thickness. The recombinant proteins caused chronic effects when
      fed, causing reductions in larval growth and food consumption by up to 60%. The
      oral toxicity of chitinase was not increased by attaching GNA in the fusion
      protein, due to degradation in the larval gut, preventing GNA acting as a
      "carrier".

PMID- 15475299
TI  - Kinetics of expression of the salivary apyrases in Triatoma infestans.
AB  - Apyrases are nucleoside triphosphate-diphosphohydrolases that remove Pi from ATP
      and ADP. The blood feeding reduviid Triatoma infestans, which transmits the
      Trypanosoma cruzi agent of Chagas disease to animals and man, presents in its
      salivary glands five apyrases with molecular masses of 88, 82, 79, 68 and 67 kDa.
      These triatomine apyrases have been associated with the prevention of ADP induced
      platelet aggregation in the host. Here we provide biochemical data showing that
      these apyrases are stored in the lumen of the salivary gland D1 pairs, and that
      about one half of the pool of the enzyme is consumed during feeding. After the
      feeding recovery of apyrases to maximal activity level takes days, thus
      suggesting de novo protein synthesis. This hypothesis is supported by
      quantitative RT-PCR analysis which shows an upregulation of the 79 kDa apyrase
      mRNA level after feeding.

PMID- 15475300
TI  - Analysis of the chitin recognition mechanism of cuticle proteins from the soft
      cuticle of the silkworm, Bombyx mori.
AB  - Insect cuticle is composed mainly of chitin, a polymer of N-acetylglucosamine,
      and chitin-binding cuticle proteins. Four major cuticle proteins, BMCP30, 22, 18,
      and 17, have been previously identified and purified from the larval cuticle of
      silkworm, B. mori. We analyzed the chitin-binding activity of BMCP30 by use of
      chitin-affinity chromatography. The pH optimum for the binding of BMCP30 to
      chitin is 6.4, which corresponds to hemolymph pH. Competition experiments using
      chitooligosaccharides suggested that BMCP30 recognizes 4-6 mer of N
      acetylglucosamine in chitin fiber as a unit for binding. The comparison of the
      binding properties of BMCP30 with those of BMCP18 showed that their binding
      activities to chitin are similar in a standard buffer but that BMCP30 binds to
      chitin more stably than BMCP18 in the presence of urea. BMCPs possess the RR-1
      form of the R&R consensus, about 70 amino acids region conserved widely among
      cuticle proteins mainly from the soft cuticle of many insect and arthropod
      species. Analysis of the binding activity using deletion mutants of BMCPs
      revealed that this type of conserved region also functions as the chitin-binding
      domain, similarly to the RR-2 region previously shown to confer chitin binding.
      Thus, the extended R&R consensus is the general chitin-binding domain of cuticle
      proteins in Arthropoda.

PMID- 15475301
TI  - Transcriptional regulation in southern corn rootworm larvae challenged by
      soyacystatin N.
AB  - When fed on a diet containing a soybean cysteine protease inhibitor soyacystatin
      N (scN), southern corn rootworm larvae exhibited increased mortality and reduced
      growth rate. scN impacted mortality in a dose-dependent manner, and its effect on
      insect growth was more severe at early developmental stages. Insects that
      survived from continuous exposure to the inhibitor at doses ranging from 0.1% to
      0.5% had less reduction in body weight during later developmental stages. This
      insensitivity as insects developed was not observed in the insect group fed on
      diet containing 0.05% scN, the lowest dose tested. Thus, individuals that
      survived the higher dose treatments may have had higher fitness under dietary
      inhibitory challenge. Subtractive hybridization and cDNA microarray analyses
      identified 29 transcript species responsive to scN. Southern corn rootworm larvae
      over-expressed cysteine and aspartic proteases to compensate for inhibition of
      digestion. Induction of a peritrophin gene suggested that strengthening the
      peritrophic membrane plays a role in coping with protease inhibitors. scN down
      regulated genes encoding proteins involved in insect metabolism and development,
      reflecting the insect's ability to reallocate resources to prioritize its defense
      response. Further, protease and the peritrophin genes were also developmentally
      regulated, which may explain the lower toxicity in older larvae than in neonates
      when first encountering dietary scN. Multiple regulatory mechanisms of counter
      defense-related genes may allow insects to evade the effect of plant defense
      proteins, and impose an obstacle to biotechnology-based insect control.

PMID- 15475302
TI  - Chlorinated tyrosine derivatives in insect cuticle.
AB  - A method for quantitative measurement of 3-monochlorotyrosine and 3,5
      dichlorotyrosine in insect cuticles is described, and it is used for
      determination of their distribution in various cuticular regions in nymphs and
      adults of the desert locust, Schistocerca gregaria. The two chlorinated tyrosine
      derivatives were present in all analyzed regions in mature adult locusts, the
      highest concentrations were found in the sclerotized cuticle of femur and tibia,
      but significant amounts were also present in the unsclerotized arthrodial
      membranes. Small amounts of the two amino acids were obtained from pharate, not
      yet sclerotized cuticle of adult femur and tibia, the amounts increased rapidly
      during the first 24 h after ecdysis and more slowly during the next two weeks.
      Control analyses using stable isotope dilution mass spectrometry have confirmed
      that the chlorinated tyrosines are not artifacts formed during sample hydrolysis.
      Mono- and dichlorotyrosine are also present in cuticular samples from other
      insect species, such as the beetle, Tenebrio molitor, the moth Hyalophora
      cecropia, the cockroach Blaberus craniifer, and the bug Rhodnius prolixus, but
      not in the sclerotized puparial cuticle of the blowfly, Calliphora vicina, or in
      sclerotized ootheca from the cockroach, Periplaneta americana. Cuticular
      sclerotization and formation of chlorotyrosines occur simultaneously in locust
      legs; sclerotized cuticles tend to have a higher content of chlorotyrosines than
      unsclerotized cuticles, but it is concluded that the chlorotyrosines are not just
      a by-product from the sclerotization process.

PMID- 15475303
TI  - The role of carboxyl, guanidine and imidazole groups in catalysis by a midgut
      trehalase purified from an insect larvae.
AB  - A trehalase (EC 3.2.1.28) of 67 kDa was purified to homogeneity from the midgut
      of Spodoptera frugiperda (Lepidoptera) larvae. The enzyme is inhibited by toxic
      beta-glucosides produced by plants (amygdalin, prunasin, salicin and phlorezin)
      and by their aglycones (mandelonitrile, phloretin). From kcat and Km values
      determined in different pHs, the pKa values of catalytic essential groups were
      calculated (pKa = 4.5 and pKa = 8.0). These pKa values agree with the ones
      determined from enzyme chemical in activation with carbodiimide and phenyl
      glyoxal, respectively, indicating that the enzyme has a carboxyl group that act
      as a nucleophile and a guanidine group that is the proton donor during the
      catalytic cycle. The enzyme has two putative subsites for glucose binding. Based
      on the protection afforded by ligands against chemical modification, the roles of
      the subsites were inferred. Thus, the one that binds the competitive inhibitors,
      methyl alpha-glucoside (MalphaGlu) and mandelonitrile, contains the catalytic
      carboxyl, whereas the other having the catalytic Arg residue binds the
      competitive inhibitor Tris. Diethyl pyrocarbonate is ineffective except in the
      presence of MalphaGlu, when it decreases trehalase activity and changes the pKa
      value of the catalytic Arg residue. This suggests that the pKa value of the Arg
      residue is modulated by a His residue located near the active site. This also
      indicates that the enzyme molecule changes its conformation when the subsite
      containing the carboxyl group is occupied. The increase in trehalase inactivation
      by phenyl glyoxal in the presence of MalphaGlu agrees with the last observation.

PMID- 15475304
TI  - Modeling the structure of the type I peritrophic matrix: characterization of a
      Mamestra configurata intestinal mucin and a novel peritrophin containing 19
      chitin binding domains.
AB  - Twelve to fourteen integral proteins were found to reside in the Type I
      peritrophic matrix (PM) of Mamestra configurata (bertha armyworm) larvae. Several
      methods were employed, including de novo peptide sequencing, the generation of a
      midgut-specific EST database and immunological screening, which led to the
      isolation of cDNAs encoding two integral PM proteins. McPM1, the largest PM
      protein described to date at 202 kDa, was comprised of a concatamer of 19 chitin
      binding domains (CBD), 12 of which resided within a central repetitive region
      consisting of six iterations of a two CBD module. The protein was found to reside
      within the PM primarily as several lower molecular weight, presumably
      proteolytically processed, forms. McMUC1 was similar in structure to other insect
      intestinal mucins (IIM) and was highly glycosylated. The expression of both
      proteins was restricted to the larval midgut. Lower molecular weight proteins
      that may represent non- and partially glycosylated forms of McMUC1 were also
      recognized by an anti-McMUC1 antiserum. These were preferentially degraded upon
      ingestion of M. configurata multi-capsid nucleopolyhedrovirus by larvae, possibly
      by a viral-encoded metalloprotease. A molecular model of PM structure is
      presented featuring the interaction of McPM1 with chitin inter-fibril junctions
      and McMUC1 with the extended chains in the internodal regions. The potential for
      interaction between PM proteins via intermolecular disulfide bond formation and
      through association of CBD with N-linked glycans is discussed.

PMID- 15475306
TI  - Conserved regulatory elements in the promoters of two allelochemical-inducible
      cytochrome P450 genes differentially regulate transcription.
AB  - CYP6B4, a cytochrome P450 gene from the tiger swallowtail Papilio glaucus, is
      transcriptionally induced in the midgut by dietary furanocoumarins, plant
      allelochemicals that can crosslink DNA in their UV-activated form. The CYP6B4
      promoter contains an overlapping EcRE/ARE/XRE-xan element similar to that used
      for basal and xanthotoxin-inducible expression of the CYP6B1 promoter from the
      black swallowtail Papilio polyxenes. Transfection of the CYP6B4 promoter:CAT
      reporter construct into Sf9 cells demonstrates that the basal and xanthotoxin
      inducible expression levels observed reflect the relative expression levels of
      this gene in the midguts of tiger swallowtail larvae. Transfections of mutant
      CYP6B4 promoter constructs into Sf9 cells indicate that the EcRE/ARE/XRE-xan
      element is necessary for CYP6B4 induction by xanthotoxin but not for its minimal
      basal expression. In addition to these elements, the CYP6B4 and CYP6B1 promoters
      also contain putative XRE-AhR elements identical to the aryl hydrocarbon response
      elements present in mammalian phase I detoxification genes. Transfections of
      CYP6B4 and CYP6B1 promoters containing EcRE/ARE/XRE-xan and XRE-AhR elements
      indicate that both are induced significantly by benzo(alpha)pyrene, an aryl
      hydrocarbon widespread in the environment, as well as by xanthotoxin, an
      allelochemical encountered in their hostplants.

PMID- 15475307
TI  - Characterisation of a serine proteinase from Penaeus vannamei haemocytes.
AB  - Serine proteinases are involved, besides digestive role, in immune response
      processes. In addition to the typical serine proteinase domain, proteinases from
      arthropod haemocytes contain so-called clip domains which are believed to exert
      regulatory functions. Clones coding for clip domain-containing serine proteinases
      were isolated from both Penaeus vannamei and Penaeus monodon haemocyte cDNA
      libraries. These proteins have most of the structural characteristics of serine
      proteinase domain, but in the clip domain there are only four cysteines, whereas
      in most other clip domains there are six. Such structures are named pseudo-clip
      domains and apparently seem to be widely distributed in Penaeid shrimp. These
      proteinases were only expressed in haemocytes and not in muscles, hypodermis,
      heart, tail stalk, pleopods or hepatopancreas.

PMID- 15475308
TI  - Effects of lactoferrin on non-specific immune responses of gilthead seabream
      (Sparus auratus L.).
AB  - The main innate cellular immune responses of gilthead seabream (Sparus auratus
      L.) leucocytes were evaluated after in vitro incubation with human lactoferrin
      (Lf). Isolated head-kidney leucocytes were incubated with 0 (control) to 1 mg ml(
      1) Lf-supplemented culture medium for 30, 120, 240 or 360 min and assayed for
      viability, peroxidase content, and respiratory burst, phagocytic and cytotoxic
      activities. Only respiratory burst activity was found to increase when using the
      highest Lf concentration (1 mg ml(-1)) and long incubation times (more than 120
      min). Seabream were fed Lf-supplemented diets (0, control, 50, 100 or 200 mg kg(
      1) diet). After 1 or 2 weeks of administration the leucocyte peroxidase content,
      respiratory burst, phagocytic and cytotoxic activities as a measure of cellular
      immune responses, as well as serum peroxidase and complement activity as a
      measure of humoral immune responses were evaluated. The results showed that Lf
      feeding at 100 mg kg(-1) diet for 1 week enhanced the cellular innate immune
      responses although only the cytotoxic activity did so significantly. The humoral
      immune response was not influenced by Lf feeding. In conclusion, Lf seems to
      affect innate immune cellular activity, mainly respiratory burst and natural
      cytotoxic activity. The possible use of Lf as an immunostimulant for farmed
      gilthead seabream is discussed.

PMID- 15475309
TI  - Mucosal response in African catfish after administration of Vibrio anguillarum O2
      antigens via different routes.
AB  - The aim of this study was to investigate the possibility of mucosal vaccination
      in African catfish (Clarias gariepinus) with Vibrio anguillarum O2 bacterins. The
      antigen was administered via different routes: anal intubation, oral
      administration, intraperitoneal injection and immersion. To monitor the antigen
      uptake, a competitive ELISA was used. The antibody response was measured using an
      indirect ELISA. Increased antibody levels were found in bile and mucus upon anal
      intubation, which was not the case after intraperitoneal injection. The data
      indicate that oral vaccination of fish may be possible when antigens can reach
      the second gut segment in sufficient quantities and in the right form as
      confirmed by the recorded substantial induction of systemic and mucosal immunity.
      The results obtained are a strong indication for mucosal immune response and the
      two compartmental models for immune response in fish.

PMID- 15475310
TI  - Use of a cDNA microarray to study immunity against viral hemorrhagic septicemia
      (VHS) in Japanese flounder (Paralichthys olivaceus) following DNA vaccination.
AB  - Japanese flounder, Paralichthys olivaceus juveniles were vaccinated against viral
      hemorrhagic septicemia (VHS) by intramuscular injection of 10 microg of a plasmid
      DNA vector which encodes the viral hemorrhagic septicemia virus (VHSV)
      glycoprotein (G) gene under the control of the cytomegalovirus promoter.
      Experimental challenge of two viral doses (1 x 10(2) TCID50 and 1 x 10(3) TCID50)
      one month post-vaccination revealed that the G gene was able to induce protective
      immunity against VHS and this lasted until 21 days after the challenge. The VHSV
      G-protein gene DNA vaccine had a high protective efficiency, giving relative
      percentage survival (RPS) values of at least 93%. The defense mechanisms
      activated by the DNA vaccine were further elucidated by microarray analysis. Non
      specific immune response genes such as NK, Kupffer cell receptor, MIP1-alpha and
      Mx1 protein gene were observed to be up-regulated by the VHSV G-protein DNA
      vaccine at 1 and 3 days post-immunization. Also, specific immune-related genes
      including the CD20 receptor, CD8 alpha chain, CD40 and B lymphocyte cell adhesion
      molecule were also up-regulated during that time. We observed significant up
      regulation of some immune-related genes that are necessary for antiviral defense.
      Significant up- and/or down-regulation of unknown genes was also observed upon
      DNA vaccination. Our results confirm previous reports that the VHSV G gene
      elicits strong humoral and cellular immune responses which may play a pivotal
      role in protecting the fish during virus infections.

PMID- 15475305
TI  - Genes transcribed in the salivary glands of female Rhipicephalus appendiculatus
      ticks infected with Theileria parva.
AB  - We describe the generation of an auto-annotated index of genes that are expressed
      in the salivary glands of four-day fed female adult Rhipicephalus appendiculatus
      ticks. A total of 9162 EST sequences were derived from an uninfected tick cDNA
      library and 9844 ESTs were from a cDNA library from ticks infected with Theileria
      parva, which develop in type III salivary gland acini. There were no major
      differences between abundantly expressed ESTs from the two cDNA libraries,
      although there was evidence for an up-regulation in the expression of some
      glycine-rich proteins in infected salivary glands. Gene ontology terms were also
      assigned to sequences in the index and those with potential enzyme function were
      linked to the Kyoto encyclopedia of genes and genomes database, allowing
      reconstruction of metabolic pathways. Several genes code for previously
      characterized tick proteins such as receptors for myokinin or ecdysteroid and an
      immunosuppressive protein. cDNAs coding for homologs of heme-lipoproteins which
      are major components of tick hemolymph were identified by searching the database
      with published N-terminal peptide sequence data derived from biochemically
      purified Boophilus microplus proteins. The EST data will be a useful resource for
      construction of microarrays to probe vector biology, vector-host and vector
      pathogen interactions and to underpin gene identification via proteomics
      approaches.

PMID- 15475311
TI  - Signal transduction of the prophenoloxidase activating system of prawn haemocytes
      triggered by CpG oligodeoxynucleotides.
AB  - Intracellular phenoloxidase (PO) activity in haemocyte lysate supernatant (HLS)
      of giant freshwater prawn (Macrobrachium rosenbergii) was shown to be enhanced by
      CpG oligodeoxynucleotide (ODN) 2006, but not by so-ODN13. When haemocytes were
      treated in vitro with 50 microg/ml of ODN2006 for 30 min, the increases in both
      intra- and extracellular stimulated PO activity (POS) and extracellular total PO
      activity (POT) and the reduction of POT suggest that the PO activity of
      haemocytes is enhanced by ODN2006 stimulation, but new prophenoloxidase (proPO)
      is not synthesised. In an attempt to determine which signal transduction pathway
      is involved in the activation of the proPO system, haemocytes were separately
      treated with activators or inhibitors of specific signalling components. The
      results show that there was an increase in both intra- and extracellular POT of
      haemocytes treated with sodium fluoride (a G-protein activator); the addition of
      phosphokinase A (PKA)-activating 8-bromo-cAMP to haemocytes only increased
      intracellular POT, and the addition of either phorbol-12-myristate-13-acetate
      (PMA; a phosphokinase C (PKC) activator) or caffeine (a phosphodiesterase
      inhibitor) only increased extracellular POT. When PMA-stimulated haemocytes were
      treated with chelerythrine (a PKC inhibitor), the induced extracellular POT was
      significantly reduced. Furthermore, the study of ODN2006-stimulated haemocytes
      treated with chelerythrine or palmitoyl-DL-carnitine (a PKC inhibitor) showed
      that the enhancement effects of ODN2006 on the intra- and extracellular POS and
      extracellular POT were significantly decreased. ODN-stimulated haemocytes treated
      with genistein (an inhibitor of protein tyrosine kinase) showed a further
      increase in extracellular POT, but the other PO activities remained the same as
      those of the ODN-stimulated group. These results suggest that the activation of
      the proPO system of prawn haemocytes, including degranulation and PO activity, is
      induced by ODN2006 via a PKC-activating signalling pathway, but negatively
      regulated via the tyrosine kinase pathway.

PMID- 15475312
TI  - Frequent occurrence of apoptosis is not associated with pathogenic infectious
      pancreatic necrosis virus (IPNV) during persistent infection.
AB  - Infectious pancreatic necrosis virus (IPNV), a member of the genus Aquabirnavirus
      and family Birnaviridae, is an unenveloped icosahedral virus with two segments of
      double-stranded RNA. IPNV causes acute infection in salmonid fry and fingerlings
      with high mortality. However, this mortality is low as the age increases and
      survivors become IPNV-carrier fish. In this study, IPNV persistent infection was
      established in rainbow trout with no clinical signs or mortality. TUNEL staining
      and immunohistochemistry showed that IPNV antigen-positive cells did not have an
      apoptotic nucleus in almost all tissue sections and leucocyte smears, indicating
      that apoptosis was not induced in IPNV antigen-positive cells. The IPNV genome
      detected by in situ RT-PCR was more frequent than detection of the IPNV antigen
      by immunohistochemistry in the kidney, spleen, and liver. This result implies
      that the successive replication would not occur in many IPNV-infected cells.
      Further, apoptotic cells were predominant in the tissue sections where the signal
      positive cells were frequently detected. Therefore, the presence of apoptosis in
      this study might be associated with host defense mechanisms, which eliminates
      IPNV-infected cells by the recognition of IPNV genome at the early stage of
      infection.

PMID- 15475313
TI  - cDNA sequence encoding an antimicrobial peptide of chelonianin from the tiger
      shrimp Penaeus monodon.

PMID- 15475314
TI  - Downward pressure on US drug prices if Kerry wins.

PMID- 15475315
TI  - Potential drug target for flesh-eating bug.

PMID- 15475316
TI  - Using SNPs to decode anthrax.

PMID- 15475317
TI  - Strategic alliance management: lessons learned from the Bayer-Millennium
      collaboration.

PMID- 15475318
TI  - Arginine-rich cell-penetrating peptides with uncharged antisense oligomers.

PMID- 15475319
TI  - MipTec: breaking down the silos of information.

PMID- 15475320
TI  - Pharmaceutical approaches to the treatment of obesity.
AB  - The recent increase in pharmaceutical companies' efforts toward the treatment of
      obesity reflects recognition of the related health risks, the growth of knowledge
      about mechanisms that control energy balance, and the potential market for new
      compounds. The current patent literature gives a picture of the targets that are
      available for pharmaceutical intervention; these include signals of satiety and
      signals related to fat storage that act in the hypothalamus. The regulation of
      energy use and storage in adipocytes and the reduction of intestinal absorption
      of energy are also pharmaceutical focus areas. The multiplicity of targets
      illustrates not only the many potential approaches to the treatment of obesity
      but also the complexity and redundancy of the processes that regulate energy
      storage in the body.

PMID- 15475321
TI  - Hsp90: the vulnerable chaperone.
AB  - The molecular chaperone Hsp90 has emerged as an important target in cancer
      treatment because of its roles in maintaining transformation and regulating the
      function of proteins involved in apoptotic, survival and growth pathways. Many
      Hsp90 inhibitors function by binding to the N-terminal ATP pocket, but the
      chaperone has many other vulnerable points. Agents that interact with its C
      terminus or modify its post-translational status represent additional ways of
      interfering with chaperone activity. This review will discuss several emerging
      classes of Hsp90 inhibitors and their modes of action.

PMID- 15475322
TI  - Proteomic patterns for early cancer detection.
AB  - The advent of proteomics has brought with it the hope of discovering novel
      biomarkers that can be used to diagnose diseases, predict susceptibility, and
      monitor progression. Much of this effort has focused on the mass spectral
      identification of the thousands of proteins that populate complex biosystems such
      as serum and tissues. A revolutionary approach in proteomic pattern analysis has
      emerged as an effective method for the early diagnosis of diseases such as
      ovarian, breast, and prostate cancer. This technology is capable of analyzing
      hundreds of clinical samples per day and has the potential to be a novel, highly
      sensitive diagnostic tool for the early detection of diseases, or as a predictor
      of response to therapy.

PMID- 15475327
TI  - Spatial dynamics of pertussis in a small region of Senegal.
AB  - Extended time-series analysis of infectious diseases raises two issues: the
      spread of disease, and its persistence in space and time. Most studies are based
      on both data and models, corresponding to conditions encountered in developed
      countries. The present work sought to determine the impact of local heterogeneity
      on these two issues, regarding pertussis in tropical conditions. First, we tested
      the 'cities and villages' model in a small community of 30 villages in rural
      Senegal. Second, we focused on the impact of population size and density, as well
      as geographic distance, on population dynamics of pertussis. Results showed that
      pertussis initially arrived in urban centres, and then spread to surrounding
      areas. Both population size and density are implicated in the persistence of
      pertussis within the study area, whereas geographical distance between villages
      is not. This is the first study on pertussis in a developing country carried out
      on a very fine spatial scale. Furthermore, it confirms previous results for
      measles in England and Wales.

PMID- 15475328
TI  - Mortality in cultures of the dinoflagellate Amphidinium carterae during culture
      senescence and darkness.
AB  - The study of cell death in higher plants and animals has revealed the existence
      of an active ('programmed') process in most types of cell, and similarities in
      cell death between plants, animals, yeast and bacteria suggest an evolutionarily
      ancient origin of programmed cell death (PCD). Despite their global importance in
      primary production, information on algal cell death is limited. Algal cell death
      could have similarities with metazoan cell death. One morphotype of metazoan PCD,
      apoptosis, can be induced by light deprivation in the unicellular chlorophyte
      Dunaliella tertiolecta. The situation in other algal taxa is less clear. We used
      a model dinoflagellate (Amphidinium carterae) to test whether mortality during
      darkness and culture senescence showed apoptotic characteristics. Using
      transmission electron microscopy, fluorescent biomarkers, chlorophyll
      fluorescence and particulate carbon analysis we analysed the process of cell
      mortality and found that light deprivation caused mass mortality. By contrast,
      fewer dead cells (5-20% of the population) were found in late-phase cultures,
      while a similar degenerate cell morphology (shrunken, chlorotic) was observed. On
      morphological grounds, our observations suggest that the apoptotic cell death
      described in D. tertiolecta does not occur in A. carterae. Greater similarity was
      found with paraptosis, a recently proposed alternative morphotype of PCD. A
      paraptotic conclusion is supported by inconclusive DNA fragmentation results. We
      emphasize the care that must be taken in transferring fundamental paradigms
      between phylogenetically diverse cell types and we argue for a greater
      consistency in the burden of proof needed to assign causality to cell death
      processes.

PMID- 15475329
TI  - Social induction of maturation and sex determination in a coral reef fish.
AB  - Labile maturation and sex determination should be advantageous where the
      probability of finding a mating partner is unpredictable. Here we tested the
      hypothesis that the presence of a potential mating partner induces maturation and
      sex determination in a coral-dwelling fish, Gobiodon erythrospilus. In natural
      populations at Lizard Island (Great Barrier Reef), single individuals were less
      likely to be mature than paired individuals and they matured at a larger size,
      indicating plasticity in the timing of maturation. By manipulating group
      structure we demonstrated that both the timing of maturation and the sex of
      maturing individuals are socially controlled. Single juveniles did not mature,
      but maturation was rapidly induced by the presence of an adult partner. In
      addition, sex determination was found to be labile, with juveniles maturing into
      the opposite sex of the partner encountered. To our knowledge, this is the first
      experimental demonstration of social induction of maturation in conjunction with
      labile sex determination at maturation in vertebrates. This flexibility enables
      individuals to maximize their reproductive success in an environment where the
      timing of mate acquisition and the sex of their future partner are unpredictable.

PMID- 15475330
TI  - Sex-specific, counteracting responses to inbreeding in a bird.
AB  - Inbreeding often depresses offspring fitness. Because females invest more than
      males in a reproductive event, inbreeding is expected to be more costly to
      mothers than fathers, creating a divergence between the reproductive interests of
      each sex and promoting sex-specific inbreeding strategies. Males and females may
      bias the probability of inbreeding by selecting copulation partners, and, in
      sexually promiscuous species, through male strategic sperm investment in
      different females and female selection of the sperm of different males. However,
      these processes are often difficult to study, and the way that different male and
      female strategies interact to determine inbreeding remains poorly understood.
      Here we demonstrate sex-specific, counteracting responses to inbreeding in the
      promiscuous red junglefowl, Gallus gallus. First, a male was just as likely to
      copulate with his full-sib sister as with an unrelated female. In addition, males
      displayed a tendency to: (i) initiate copulation faster when exposed to an
      unrelated female than when exposed to a sister, and (ii) inseminate more sperm
      into sisters than into unrelated females. Second, females retained fewer sperm
      following insemination by brothers, thus reducing the risk of inbreeding and
      counteracting male inbreeding strategies.

PMID- 15475331
TI  - Delayed plumage maturation increases overwinter survival in North Island robins.
AB  - Many bird species show delayed plumage maturation (DPM), retaining sub-adult
      plumage until after their first breeding season. Most explanations assume that
      DPM increases fitness over the breeding season. However, unless birds undergo a
      full moult before breeding, DPM could also be an adaptation to increase survival
      over the previous winter. The winter adaptation hypothesis has never been tested
      owing to the difficulty of measuring overwinter survival. We experimentally
      tested this hypothesis in North Island robins (Petroica longipes) using a closed
      island population where we could accurately estimate survival. The experiment
      involved dyeing 41 juveniles to mimic adult males, and comparing their survival
      with 41 control juveniles treated with the same peroxide base minus the pigment.
      The population was monitored with a series of resighting surveys, and mark
      recapture analysis used to estimate overwinter survival. Survival probability was
      estimated to be 10% for dyed birds versus 61% for control birds in 2001, and 29%
      for dyed birds versus 40% for control birds in the winter of 2002, supporting the
      winter adaptation hypothesis for DPM. Access to suitable habitat is the key
      factor limiting juvenile survival in this population, and the locations where
      dyed juveniles were sighted suggest that they were often excluded from suitable
      areas.

PMID- 15475332
TI  - Fish can encode order in their spatial map.
AB  - Animals must often orient through areas that are larger than their perceptual
      range. The blind Mexican cave fish, Astyanax fasciatus, depends on detecting self
      induced near-field wave perturbations by objects via the use of its lateral line
      organ. Its perceptual range (less than or equal to 0.05 m) is greatly exceeded by
      its ecological ranging requirements (ca. 30 m). Although known to possess a
      spatial map of its environment, it is not known how this fish links places (or
      the area over which the perceptual range extends) together. Using the blind cave
      fish's propensity to accelerate when faced with objects or environments that are
      recognizably different, I used a behavioural assay to test whether fishes can
      learn and remember the order of a landmark sequence. I show, to my knowledge for
      the first time, that blind Mexican cave fish can encode order in their spatial
      map. The ability to represent the order in which a series of places are spatially
      linked is a powerful tool for animals that must orient beyond the limit of their
      perceptual range. The resulting spatial map would be analogous to a jigsaw
      puzzle, where each piece represents a place whose size is constrained by the
      animal's perceptual range.

PMID- 15475333
TI  - Evasive mimicry: when (if ever) could mimicry based on difficulty of capture
      evolve?
AB  - We elucidate the conditions under which an easy-to-catch edible prey species may
      evolve to resemble another edible species that is much more difficult to capture
      ('evasive Batesian mimicry'), and the conditions under which two or more edible
      but hard-to-catch species evolve a common resemblance ('evasive Mullerian
      mimicry'). Using two complementary mathematical models, we argue that both
      phenomena are logically possible but that several factors will limit the
      prevalence of these forms of mimicry in nature. Evasive Batesian mimicry is most
      likely to arise when it is costly in time or energy for the predator species to
      pursue evasive prey, when mimics are encountered less frequently than evasive
      models and where there are abundant alternative prey. Evasive Mullerian mimicry,
      by contrast, is most likely to arise when evasive prey species differ in
      abundance, predators are slow to learn to avoid evasive prey and evading capture
      is costly to the prey. Unequivocal evidence for evasive Batesian or Mullerian
      mimicry has not yet been demonstrated in the field, and we argue that more
      empirical work is needed to test whether putative examples are indeed a result of
      selection to signal difficulty of capture.

PMID- 15475334
TI  - The effect of autocorrelation in environmental variability on the persistence of
      populations: an experimental test.
AB  - Despite its significance regarding the conservation and management of biological
      resources, the body of theory predicting that the correlation between successive
      environmental states can profoundly influence extinction has not been empirically
      validated. Identical clonal populations from a model experimental system based on
      the collembolan Folsomia candida were used in the present study to investigate
      the effect of environmental autocorrelation on time to extinction. Environmental
      variation was imposed by variable implementation (present/absent) of a culling
      procedure according to treatments that represented six patterns of environmental
      autocorrelation. The average number of culling events was held constant across
      treatments but, as environmental autocorrelation increased, longer runs of both
      favourable and unfavourable culling tended to occur. While no difference was
      found among the survival functions for the various treatments, the time taken for
      50% of the component populations to become extinct decreased significantly with
      increasing environmental autocorrelation. Similarly, analysis of all extinct
      populations demonstrated that time to extinction was shortened as environmental
      autocorrelation increased. However, this acceleration of extinction can be fully
      offset if sequential introduction is used in place of simultaneous introduction
      when founding the populations.

PMID- 15475335
TI  - Parasite-mediated selection in experimental metapopulations of Daphnia magna.
AB  - In metapopulations, only a fraction of all local host populations may be infected
      with a given parasite species, and limited dispersal of parasites suggests that
      colonization of host populations by parasites may involve only a small number of
      parasite strains. Using hosts and parasites obtained from a natural
      metapopulation, we studied the evolutionary consequences of invasion by single
      strains of parasites in experimental populations of the cyclical parthenogen
      Daphnia magna. In two experiments, each spanning approximately one season, we
      monitored clone frequency changes in outdoor container populations consisting of
      13 and 19 D. magna clones, respectively. The populations were either infected
      with single strains of the microsporidian parasites Octosporea bayeri or
      Ordospora colligata or left unparasitized. In both experiments, infection changed
      the representation of clones over time significantly, indicating parasite
      mediated evolution in the experimental populations. Furthermore, the two parasite
      species changed clone frequencies differently, suggesting that the interaction
      between infection and competitive ability of the hosts was specific to the
      parasite species. Taken together, our results suggest that parasite strains that
      invade local host populations can lead to evolutionary changes in the genetic
      composition of the host population and that this change is parasite-species
      specific.

PMID- 15475336
TI  - Selection on insect immunity in the wild.
AB  - The strength of selection on immune function in wild populations has only been
      examined in a few vertebrate species. We report the results from a study
      measuring selection on a key insect immune enzyme, phenoloxidase (PO), in a wild
      population of the damselfly Calopteryx xanthostoma. We followed individually
      marked males from the pre-reproductive adult phase and recorded their lifetime
      mating success. We found positive selection on PO activity in response to an
      immune insult, but no selection on wing-spot quality, a trait actively displayed
      to females during courtship. We suggest that positive selection on PO activity in
      the year of study may be explained by annual fluctuations in parasite loads.

PMID- 15475337
TI  - Population control of the malaria vector Anopheles pseudopunctipennis by habitat
      manipulation.
AB  - Insect vector-borne diseases continue to present a major challenge to human
      health. Understanding the factors that regulate the size of mosquito populations
      is considered fundamental to the ability to predict disease transmission rates
      and for vector population control. The mosquito, Anopheles pseudopunctipennis, a
      vector of Plasmodium spp., breeds in riverside pools containing filamentous algae
      in Mesoamerica. Breeding pools along 3 km sections of the River Coatan, Chiapas,
      Mexico were subjected to algal extraction or left as controls in a cross-over
      trial extending over 2 years. Initial densities of An. pseudopunctipennis larvae
      were directly proportional to the prevalence of filamentous algae in each
      breeding site. The extraction of algae brought about a striking decline in the
      density of An. pseudopunctipennis larvae sustained for about six weeks, and a
      concurrent reduction in the adult population in both years of the study. Mark
      release experiments indicated that dispersal from adjacent untreated areas was
      unlikely to exert an important influence on the magnitude of mosquito control
      that we observed. Habitat manipulation by extraction of filamentous algae offers
      a unique opportunity for sustainable control of this malaria vector. This
      technique may represent a valuable intervention, complimenting insecticide
      spraying of households, to minimize Plasmodium transmission rates in Mesoamerica.

PMID- 15475338
TI  - Diet-dependent effects of gut bacteria on their insect host: the symbiosis of
      Erwinia sp. and western flower thrips.
AB  - Studies on bacteria in the gut of insect species are numerous, but their focus is
      hardly ever on the impact on host performance. We showed earlier that Erwinia
      bacteria occur in the gut of western flower thrips, most probably acquired during
      feeding. Here, we investigate whether thrips gain a net benefit or pay a net cost
      because of these gut bacteria. On a diet of cucumber leaves, the time to maturity
      is shorter and the oviposition rate is higher in thrips with bacteria than in
      thrips without (aposymbionts). When fed on cucumber leaves and pollen,
      aposymbionts develop faster and lay more eggs. So Erwinia bacteria benefit or
      parasitize their thrips hosts depending on the diet, which is in accordance with
      theoretical predictions for fitness of organisms engaged in symbiotic
      interactions. Possibly, the transmission of gut bacteria has not become strictly
      vertical because of this diet-dependent fitness variability.

PMID- 15475339
TI  - Managing the evolution of Bacillus thuringiensis resistance in natural
      populations of the European corn borer, Ostrinia nubilalis: host plant, host race
      and pherotype of adult males at aggregation sites.
AB  - The European corn borer (ECB) consists of at least two, genetically
      differentiated host races: one feeding on maize, the other feeding on mugwort and
      hop. It is unclear to what extent individuals feeding on these, or other host
      plants, contribute to natural ECB populations. The mechanisms underlying the
      genetic differentiation between both races are not well understood; they may
      include sexual attraction via different pheromone blends (E or Z) and differences
      in the location of mating sites. We caught adult males with traps baited with the
      E or the Z blend at hop, maize, and 'mixed' sites. We determined their probable
      host race by allozyme-based genetic assignment, and the photosynthetic type of
      their host plant by stable carbon isotope analysis. Most individuals caught in Z
      traps had emerged from a C(4)-type plant and belonged to the maize race, whereas
      most individuals caught in E traps had emerged from C(3)-type plants and were but
      weakly differentiated from the hop-mugwort race, suggesting a strong, though not
      absolute, correspondence between host plant, host race and pherotype. We also
      found that although spatial segregation may contribute to genetic isolation
      between host races, moths of both host races may be present at a given location.
      Regarding the management of Bacillus thuringiensis (Bt) maize, our results
      indicate that, at least at the present study sites, it is unlikely that any wild
      or cultivated C(3)-type plant species could be a source of susceptible
      individuals that would mate randomly with Bt-resistant Z-C(4) moths emerging from
      Bt-maize fields.

PMID- 15475340
TI  - Transmission rates and adaptive evolution of pathogens in sympatric heterogeneous
      plant populations.
AB  - Diversification in agricultural cropping patterns is widely practised to delay
      the build-up of virulent races that can overcome host resistance in pathogen
      populations. This can lead to balanced polymorphism, but the long-term
      consequences of this strategy for the evolution of crop pathogen populations are
      still unclear. The widespread occurrence of sibling species and reproductively
      isolated sub-species among fungal and oomycete plant pathogens suggests that
      evolutionary divergence is common. This paper develops a mathematical model of
      host-pathogen interactions using a simple framework of two hosts to analyse the
      influences of sympatric host heterogeneity on the long-term evolutionary
      behaviour of plant pathogens. Using adaptive dynamics, which assumes that
      sequential mutations induce small changes in pathogen fitness, we show that
      evolutionary outcomes strongly depend on the shape of the trade-off curve between
      pathogen transmission on sympatric hosts. In particular, we determine the
      conditions under which the evolutionary branching of a monomorphic into a
      dimorphic population occurs, as well as the conditions that lead to the evolution
      of specialist (single host range) or generalist (multiple host range) pathogen
      populations.

PMID- 15475341
TI  - Environmental energy and evolutionary rates in flowering plants.
AB  - The latitudinal gradient in species richness is a pervasive feature of the living
      world, but its underlying causes remain unclear. We evaluated the hypothesis that
      environmental energy drives evolutionary rates and thereby diversification in
      flowering plants. We estimated energy levels across angiosperm family
      distributions in terms of evapotranspiration, temperature and UV radiation taken
      from satellite and climate databases. Using the most comprehensive DNA-based
      phylogenetic tree for angiosperms to date, analysis of 86 sister-family
      comparisons shows that molecular evolutionary rates have indeed been faster in
      high-energy regions, but that this is not an intermediate step between energy and
      diversity. Energy has strong, but independent effects on both species richness
      and molecular evolutionary rates.

PMID- 15475342
TI  - The effectiveness of five strategies for the prevention of gastrointestinal
      toxicity induced by non-steroidal anti-inflammatory drugs: systematic review.
AB  - OBJECTIVES: To assess the effectiveness of five gastroprotective strategies for
      people taking non-steroidal anti-inflammatory drugs (NSAIDs)--H2 receptor
      antagonists plus non-selective (or cyclo-oxygenase-1) NSAIDs; proton pump
      inhibitors plus non-selective NSAIDs; misoprostol plus non-selective NSAIDs; COX
      2 selective NSAIDs; or COX-2 specific NSAIDs--in reducing serious
      gastrointestinal complications, symptomatic ulcers, serious cardiovascular or
      renal disease, and deaths, and improving quality of life. DATA SOURCES: The
      Cochrane Library, Medline, Embase, Current Controlled Trials, and System for
      Information on Grey Literature in Europe (SIGLE) were searched to May 2002.
      Bibliographies and author contacts were used to identify further studies; non
      English articles were included. REVIEW METHODS: Trial selection, data extraction,
      and quality assessment were performed independently, in duplicate. Articles were
      rejected only if the study was not a randomised controlled trial; did not assess
      a gastroprotective strategy versus placebo; included exclusively children or
      healthy volunteers; lasted less than 21 days; or no review outcomes were
      measured. Quality assessment included allocation concealment and baseline
      similarity. Random effects meta-analysis, meta-regression and subgrouping were
      used to pool effects and analyse associations with length of follow up, mean age,
      and baseline gastrointestinal status. Heterogeneity was examined and sensitivity
      analyses performed. RESULTS: Of 112 included randomised controlled trials (74 666
      participants), five were judged to be at low risk of bias, and 138 deaths and 248
      serious gastrointestinal events were reported overall. On comparing
      gastroprotective strategies versus placebo we found no evidence of effectiveness
      of H2 receptor antagonists for any primary outcomes (few events reported); proton
      pump inhibitors may reduce the risk of symptomatic ulcers (relative risk 0.09,
      95% confidence interval 0.02 to 0.47); misoprostol reduces the risk of serious
      gastrointestinal complications (0.57, 0.36 to 0.91) and symptomatic ulcers (0.36,
      0.20 to 0.67); COX-2 selectives reduce the risk of symptomatic ulcers (0.41, 0.26
      to 0.65) and COX-2 specifics reduce the risk of symptomatic ulcers (0.49, 0.38 to
      0.62) and possibly serious gastrointestinal complications (0.55, 0.38 to 0.80).
      All strategies except COX-2 selectives reduce the risk of endoscopic ulcers (at
      least 3 mm in diameter). CONCLUSIONS: Misoprostol, COX-2 specific and selective
      NSAIDs, and probably proton pump inhibitors significantly reduce the risk of
      symptomatic ulcers, and misoprostol and probably COX-2 specifics significantly
      reduce the risk of serious gastrointestinal complications, but data quality is
      low. More data on H2 receptor antagonists and proton pump inhibitors are needed,
      as is better reporting of rare but important outcomes.

PMID- 15475343
TI  - Interaction of West Nile virus with alpha v beta 3 integrin mediates virus entry
      into cells.
AB  - The functional receptor for the flavivirus West Nile (WNV) infection has been
      characterized in this study with a combination of biochemical and molecular
      approaches. A 105-kDa protease-sensitive glycoprotein that binds WNV was isolated
      from the plasma membrane of cells permissive to WNV infection. The protein was
      subjected to peptide sequencing, and this glycoprotein was identified as a member
      of the integrin superfamily. Infection of WNV was shown to be markedly inhibited
      in Vero cells pretreated with blocking antibodies against alpha(v)beta(3)
      integrin and its subunits by receptor competition assay. It was also noted that
      cells pretreated with antibodies against alpha(v)beta(3) integrin can effectively
      inhibit flavivirus Japanese encephalitis but to a lesser extent flavivirus dengue
      infections. West Nile virus entry is independent of divalent cations and is not
      highly blocked by arginine-glycine-aspartic acid (RGD) peptides, suggesting that
      the interaction between the virus and alpha(v)beta(3) integrin is not highly
      dependent on the classical RGD binding motif. In addition, gene silencing of the
      beta(3) integrin subunit in cells has resulted in cells largely resistant to WNV
      infection. In contrast, expression of recombinant human beta(3) integrin
      substantially increased the permissiveness of CS-1 melanoma cells for WNV
      infection. Soluble alpha(v)beta(3) integrin can also effectively block WNV
      infection in a dose-dependent manner. Furthermore, WNV infection also triggered
      the outside-in signaling pathway via the activation of integrin-associated focal
      adhesion kinase. The identification of alpha(v)beta(3) integrin as a receptor for
      WNV provides insight into virus-receptor interaction, hence creating
      opportunities in the development of anti-viral strategies against WNV infection.

PMID- 15475344
TI  - Structure-based engineering of Alcaligenes xylosoxidans copper-containing nitrite
      reductase enhances intermolecular electron transfer reaction with pseudoazurin.
AB  - The intermolecular electron transfer from Achromobacter cycloclastes pseudoazurin
      (AcPAZ) to wild-type and mutant Alcaligenes xylosoxidans nitrite reductases
      (AxNIRs) was investigated using steady-state kinetics and electrochemical
      methods. The affinity and the electron transfer reaction constant (k(ET)) are
      considerably lower between AcPAZ and AxNIR (K(m) = 1.34 mM and k(ET) = 0.87 x
      10(5) M(-1) s(-1)) than between AcPAZ and its cognate nitrite reductase (AcNIR)
      (K(m) = 20 microM and k(ET) = 7.3 x 10(5) M(-1) s(-1)). A negatively charged
      hydrophobic patch, comprising seven acidic residues around the type 1 copper site
      in AcNIR, is the site of protein-protein interaction with a positively charged
      hydrophobic patch on AcPAZ. In AxNIR, four of the negatively charged residues
      (Glu-112, Glu-133, Glu-195, and Asp-199) are conserved at the corresponding
      positions of AcNIR, whereas the other three residues are not acidic amino acids
      but neutral amino acids (Ala-83, Ala-191, and Gly-198). Seven mutant AxNIRs with
      additional negatively charged residues surrounding the hydrophobic patch of AxNIR
      (A83D, A191E, G198E, A83D/A191E, A93D/G198E, A191E/G198E, and A83D/A191E/G198E)
      were prepared to enhance the specificity of the electron transport reaction
      between AcPAZ and AxNIR. The k(ET) values of these mutants become progressively
      larger as the number of mutated residues increases. The K(m) and k(ET) values of
      A83D/A191E/G198E (K(m) = 88 microM and k(ET) = 4.1 x 10(5) M(-1) s(-1)) are 15
      fold smaller and 4.7-fold larger than those of wild-type AxNIR, respectively.
      These results suggest that the introduction of negatively charged residues into
      the docking surface of AxNIR facilitates both the formation of electron transport
      complex and the electron transfer reaction.

PMID- 15475345
TI  - The mutation F227I increases the coupling of metal ion transport in DCT1.
AB  - Metal ion transport by DCT1, a member of the natural resistance-associated
      macrophage protein family, is driven by protons. The stoichiometry of the proton
      to metal ion is variable, and under optimal transport conditions, more than 10
      protons are co-transported with a single metal ion. To understand this phenomenon
      better, we used site-directed mutagenesis of DCT1 and analyzed the mutants by
      complementation of yeast suppressor of mitochondria import function-null mutants
      and electrophysiology with Xenopus oocytes. The mutation F227I resulted in an
      increase of up to 14-fold in the ratio between metal ions to protons transported.
      This observation suggests that low metal ion to proton transport of DCT1
      resulting from a proton slippage is not a necessity of the transport mechanism in
      which positively charged protons are driving two positive charges of the metal
      ion in the same direction. It supports the idea that the proton slippage has a
      physiological advantage, and the proton slip was positively selected during the
      evolution of DCT1.

PMID- 15475346
TI  - EPR spectroscopic characterization of the manganese center and a free radical in
      the oxalate decarboxylase reaction: identification of a tyrosyl radical during
      turnover.
AB  - Several molecular mechanisms for cleavage of the oxalate carbon-carbon bond by
      manganese-dependent oxalate decarboxylase have recently been proposed involving
      high oxidation states of manganese. We have examined the oxalate decarboxylase
      from Bacillus subtilis by electron paramagnetic resonance in perpendicular and
      parallel polarization configurations to test for the presence of such species in
      the resting state and during enzymatic turnover. Simulation and the position of
      the half-field Mn(II) line suggest a nearly octahedral metal geometry in the
      resting state. No spectroscopic signature for Mn(III) or Mn(IV) is seen in
      parallel mode EPR for samples frozen during turnover, consistent either with a
      large zero-field splitting in the oxidized metal center or undetectable levels of
      these putative high-valent intermediates in the steady state. A narrow,
      featureless g = 2.0 species was also observed in perpendicular mode in the
      presence of substrate, enzyme, and dioxygen. Additional splittings in the signal
      envelope became apparent when spectra were taken at higher temperatures. Isotopic
      editing resulted in an altered line shape only when tyrosine residues of the
      enzyme were specifically deuterated. Spectral processing confirmed multiple
      splittings with isotopically neutral enzyme that collapsed to a single prominent
      splitting in the deuterated enzyme. These results are consistent with formation
      of an enzyme-based tyrosyl radical upon oxalate exposure. Modestly enhanced
      relaxation relative to abiological tyrosyl radicals was observed, but site
      directed mutagenesis indicated that conserved tyrosine residues in the active
      site do not host the unpaired spin. Potential roles for manganese and a
      peripheral tyrosyl radical during steady-state turnover are discussed.

PMID- 15475347
TI  - My brief encounter with the phosphoinositides and IP3.

PMID- 15475348
TI  - Human Nischarin/imidazoline receptor antisera-selected protein is targeted to the
      endosomes by a combined action of a PX domain and a coiled-coil region.
AB  - Around 50 mammalian and 15 yeast proteins are known to contain the phox (PX)
      domain, the majority (about 30) of which is classified as sorting nexins (SNXs).
      The PX domain, a hallmark of these proteins, is a conserved stretch of about 120
      amino acids and is recently shown to mediate phosphoinositide binding. A few PX
      domain proteins (including some SNXs) have been shown to participate in diverse
      cellular processes such as protein sorting, signal transduction, and vesicle
      fusion. In this report, we present our results supporting a role of human IRAS to
      act as a SNX. The mouse homologue, previously identified as Nischarin, has been
      shown to interact with the alpha(5) subunit of integrin and inhibit cell
      migration (Alahari, S. K., Lee J. W., and Juliano R. L. (2000) J. Cell Biol. 51,
      1141-1154). Its human homologue (imidazoline receptor antisera-selected (IRAS)),
      on the other hand, contains an NH(2)-terminal extension and is a larger protein
      of 1504 amino acids consisting of an NH(2)-terminal PX domain, 5 putative leucine
      rich repeats, a predicted coiled-coil domain, and a long COOH-terminal region. We
      show that it has the ability to homo-oligomerize via its coiled-coil region. The
      PX domain of IRAS is essential for association with phosphatidylinositol 3
      phosphate-enriched endosomal membranes. However, the PX domain of IRAS alone is
      insufficient for its localization to endosomes, unless the coiled-coil domain was
      included or it is artificially dimerized by glutathione S-transferase.
      Interaction of human IRAS with alpha(5) integrin is not affected by the NH(2)
      terminal extension, and overexpression of IRAS could cause a redistribution of
      surface alpha(5) integrin to intracellular endosomal structures.

PMID- 15475349
TI  - In the Archaea Haloferax volcanii, membrane protein biogenesis and protein
      synthesis rates are affected by decreased ribosomal binding to the translocon.
AB  - In the haloarchaea Haloferax volcanii, ribosomes are found in the cytoplasm and
      membrane-bound at similar levels. Transformation of H. volcanii to express
      chimeras of the translocon components SecY and SecE fused to a cellulose-binding
      domain substantially decreased ribosomal membrane binding, relative to non
      transformed cells, likely due to steric hindrance by the cellulose-binding
      domain. Treatment of cells with the polypeptide synthesis terminator puromycin,
      with or without low salt washes previously shown to prevent in vitro ribosomal
      membrane binding in halophilic archaea, did not lead to release of translocon
      bound ribosomes, indicating that ribosome release is not directly related to the
      translation status of a given ribosome. Release was, however, achieved during
      cell starvation or stationary growth, pointing at a regulated manner of ribosomal
      release in H. volcanii. Decreased ribosomal binding selectively affected membrane
      protein levels, suggesting that membrane insertion occurs co-translationally in
      Archaea. In the presence of chimera-incorporating sterically hindered
      translocons, the reduced ability of ribosomes to bind in the transformed cells
      modulated protein synthesis rates over time, suggesting that these cells manage
      to compensate for the reduction in ribosome binding. Possible strategies for this
      compensation, such as a shift to a post-translational mode of membrane protein
      insertion or maintained ribosomal membrane-binding, are discussed.

PMID- 15475350
TI  - Crystal structure of the Kelch domain of human Keap1.
AB  - Keap1 is a substrate adaptor protein for an ubiquitin ligase complex that targets
      the Nrf2 transcription factor for degradation. Keap1 binds Nrf2 through its C
      terminal Kelch domain, which contains six copies of the evolutionarily conserved
      kelch repeat sequence motif. The structure of the Kelch domain from human Keap1
      has been determined by x-ray crystallography to a resolution of 1.85 A. The Kelch
      domain forms a 6-bladed beta-propeller structure, with residues at the C terminus
      forming the first strand in the first blade. Key structural roles have been
      identified for the highly conserved glycine, tyrosine, and tryptophan residues
      that define the kelch repeat sequence motif. In addition, we show that
      substitution of a single amino acid located within a loop that extends out from
      the bottom of the beta-propeller structure abolishes binding of Nrf2. The
      structure of the Kelch domain of Keap1 represents a high quality model for the
      superfamily of eukaryotic kelch repeat proteins and provides insight into how
      disease-causing mutations perturb the structural integrity of the Kelch domain.

PMID- 15475351
TI  - FhuD1, a ferric hydroxamate-binding lipoprotein in Staphylococcus aureus: a case
      of gene duplication and lateral transfer.
AB  - Staphylococcus aureus can utilize ferric hydroxamates as a source of iron under
      iron-restricted growth conditions. Proteins involved in this transport process
      are: FhuCBG, which encodes a traffic ATPase; FhuD2, a post-translationally
      modified lipoprotein that acts as a high affinity receptor at the cytoplasmic
      membrane for the efficient capture of ferric hydroxamates; and FhuD1, a protein
      with similarity to FhuD2. Gene duplication likely gave rise to fhuD1 and fhuD2.
      While the genomic locations of fhuCBG and fhuD2 in S. aureus strains are
      conserved, both the presence and the location of fhuD1 are variable. The apparent
      redundancy of FhuD1 led us to examine the role of this protein. We demonstrate
      that FhuD1 is expressed only under conditions of iron limitation through the
      regulatory activity of Fur. FhuD1 fractions with the cell membrane and binds
      hydroxamate siderophores but with lower affinity than FhuD2. Using small angle x
      ray scattering, the solution structure of FhuD1 resembles that of FhuD2, and only
      a small conformational change is associated with ferrichrome binding. FhuD1,
      therefore, appears to be a receptor for ferric hydroxamates, like FhuD2. Our data
      to date suggest, however, that FhuD1 is redundant to FhuD2 and plays a minor role
      in hydroxamate transport. However, given the very real possibility that we have
      not yet identified the proper conditions where FhuD1 does provide an advantage
      over FhuD2, we anticipate that FhuD1 serves an enhanced role in the transport of
      untested hydroxamate siderophores and that it may play a prominent role during
      the growth of S. aureus in its natural environments.

PMID- 15475352
TI  - Models of the cooperative mechanism for Rho effector recognition: implications
      for RhoA-mediated effector activation.
AB  - Activated GTPases of the Rho family regulate a spectrum of functionally diverse
      downstream effectors, initiating a network of signal transduction pathways by
      interaction and activation of effector proteins. Although effectors are defined
      as proteins that selectively bind the GTP-bound state of the small GTPases, there
      have been also several indications for a nucleotide-independent binding mode. By
      characterizing the molecular mechanism of RhoA interaction with its effectors, we
      have determined the equilibrium dissociation constants of several Rho-binding
      domains of three different effector proteins (Rhotekin, ROCKI/ROK beta/p160ROCK,
      PRK1/PKNalpha where ROK is RhoA-binding kinase) for both RhoA.GDP and RhoA.GTP
      using fluorescence spectroscopy. In addition, we have identified two novel Rho
      interacting domains in ROCKI, which bind RhoA with high affinity but not Cdc42 or
      Rac1. Our results, together with recent structural data, support the notion of
      multiple effector-binding sites in RhoA and strongly indicate a cooperative
      binding mechanism for PRK1 and ROCKI that may be the molecular basis of Rho
      mediated effector activation.

PMID- 15475353
TI  - Identification of amino acid residues that direct differential ligand selectivity
      of mammalian and nonmammalian V1a type receptors for arginine vasopressin and
      vasotocin. Insights into molecular coevolution of V1a type receptors and their
      ligands.
AB  - Arginine vasotocin (VT) is the ortholog in all nonmammalian vertebrates of
      arginine vasopressin (AVP) in mammals. We have previously cloned an amphibian
      V1atype vasotocin receptor (VT1R) that exhibited higher sensitivity for VT than
      AVP, while the mammalian V1a type receptor (V1aR) responded better to AVP than
      VT. In the present study, we identified the amino acid residues that confer
      differential ligand selectivity for AVP and VT between rat V1aR and bullfrog VT1R
      (bfVT1R). A chimeric rat V1aR having transmembrane domain (TMD) VI to the
      carboxyl-terminal tail (C-tail) of bfVT1R showed a reverse ligand preference for
      AVP and VT, whereas a chimeric VT1R with TMD VI to the C-tail of rat V1aR showed
      a great increase in sensitivity for AVP. A single mutation (Ile(315(6.53)) to
      Thr) in TMD VI of V1aR increased the sensitivity for VT, while a single mutation
      (Phe(313(6.51)) to Tyr or Pro(334(7.33)) to Thr) reduced sensitivity toward AVP.
      Interestingly the triple mutation (Phe(313(6.51)) to Tyr, Ile(6.53) to Thr, and
      Pro(7.33) to Thr) of V1aR increased sensitivity to VT but greatly reduced
      sensitivity to AVP, behaving like bfVT1R. Further, like V1aR, a double mutant
      (Tyr(306(6.51)) to Phe and Thr(327(7.33)) to Pro) of bfVT1R showed an increased
      sensitivity to AVP. These results suggest that Phe/Tyr(6.51), Ile/Thr(6.53), and
      Pro/Thr(7.33) are responsible for the differential ligand selectivity between rat
      V1aR and bfVT1R. This information regarding the molecular interaction of VT/AVP
      with their receptors may have important implications for the development of novel
      AVP analogs.

PMID- 15475354
TI  - Dissection of antibacterial and toxic activity of melittin: a leucine zipper
      motif plays a crucial role in determining its hemolytic activity but not
      antibacterial activity.
AB  - Melittin, a naturally occurring antimicrobial peptide, exhibits strong lytic
      activity against both eukaryotic and prokaryotic cells. Despite a tremendous
      amount of work done, very little is known about the amino acid sequence, which
      regulates its toxic activity. With the goal of understanding the basis of toxic
      activity and poor cell selectivity in melittin, a leucine zipper motif has been
      identified. To evaluate the possible structural and functional roles of this
      motif, melittin and its two analogs, after substituting the heptadic leucine by
      alanine, were synthesized and characterized. Functional studies indicated that
      alanine substitution in the leucine zipper motif resulted in a drastic reduction
      of the hemolytic activity of melittin. However, interestingly, both the designed
      analogs exhibited antibacterial activity comparable to melittin. Mutations caused
      a significant decrease in the membrane permeability of melittin in zwitterionic
      but not in negatively charged lipid vesicles. Although both the analogs exhibited
      similar secondary structures in the presence of negatively charged lipid vesicles
      as melittin, they failed to adopt a significant helical structure in the presence
      of zwitterionic lipid vesicles. Results suggest that the substitution of heptadic
      leucine by alanine impaired the assembly of melittin in an aqueous environment
      and its localization only in zwitterionic but not in negatively charged membrane.
      Altogether, the results suggest the identification of a structural element in
      melittin, which probably plays a prominent role in regulating its toxicity but
      not antibacterial activity. The results indicate that cell selectivity in some
      antimicrobial peptides can probably be introduced by modulating their assembly in
      an aqueous environment.

PMID- 15475355
TI  - Role of the retinal hydrogen bond network in rhodopsin Schiff base stability and
      hydrolysis.
AB  - Little is known about the molecular mechanism of Schiff base hydrolysis in
      rhodopsin. We report here our investigation into this process focusing on the
      role of amino acids involved in a hydrogen bond network around the retinal Schiff
      base. We find conservative mutations in this network (T94I, E113Q, S186A, E181Q,
      Y192F, and Y268F) increase the activation energy (E(a)) and abolish the concave
      Arrhenius plot normally seen for Schiff base hydrolysis in dark state rhodopsin.
      Interestingly, two mutants (T94I and E113Q) show dramatically faster rates of
      Schiff base hydrolysis in dark state rhodopsin, yet slower hydrolysis rates in
      the active MII form. We find deuterium affects the hydrolysis process in wild
      type rhodopsin, exhibiting a specific isotope effect of approximately 2.5, and
      proton inventory studies indicate that multiple proton transfer events occur
      during the process of Schiff base hydrolysis for both dark state and MII forms.
      Taken together, our study demonstrates the importance of the retinal hydrogen
      bond network both in maintaining Schiff base integrity in dark state rhodopsin,
      as well as in catalyzing the hydrolysis and release of retinal from the MII form.
      Finally, we note that the dramatic alteration of Schiff base stability caused by
      mutation T94I may play a causative role in congenital night blindness as has been
      suggested by the Oprian and Garriga laboratories.

PMID- 15475356
TI  - Glucose-stimulated protein synthesis in pancreatic beta-cells parallels an
      increase in the availability of the translational ternary complex (eIF2-GTP.Met
      tRNAi) and the dephosphorylation of eIF2 alpha.
AB  - In pancreatic beta-cells, glucose causes a rapid increase in the rate of protein
      synthesis. However, the mechanism by which this occurs is poorly understood. In
      this report, we demonstrate, in the pancreatic beta-cell line MIN6, that glucose
      stimulates the recruitment of ribosomes onto the mRNA, indicative of an increase
      in the rate of the initiation step of protein synthesis. This increase in the
      rate of initiation is not mediated through an increase in the availability of the
      initiation complex eIF4F, because glucose is unable to stimulate eIF4F assembly
      or, in the absence of amino acids, modulate the phosphorylation status of 4E-BP1.
      Moreover, in MIN6 cells and isolated islets of Langerhans, rapamycin, an
      inhibitor of the mammalian target of rapamycin, only partially inhibited glucose
      stimulated protein synthesis. However, we show that glucose stimulates the
      dephosphorylation of eIF2 alpha in MIN6 cells and the assembly of the
      translational ternary complex, eIF2-GTP.Met-tRNAi, in both MIN6 cells and islets
      of Langerhans. The changes in the phosphorylation of eIF2 alpha are not mediated
      by the PKR-like endoplasmic reticulum eIF2 alpha kinase (PERK), because PERK is
      not phosphorylated at low glucose concentrations and overexpression of a dominant
      negative form of PERK has no significant effect on either glucose-stimulated
      protein synthesis or the phosphorylation of eIF2 alpha. Taken together, these
      results indicate that glucose-stimulated protein synthesis in pancreatic beta
      cells is regulated by a mechanism largely independent of the activity of
      mammalian target of rapamycin, but which is likely to be dependent on the
      availability of the translational ternary complex, regulated by the
      phosphorylation status of eIF2 alpha.

PMID- 15475357
TI  - PDILT, a divergent testis-specific protein disulfide isomerase with a non
      classical SXXC motif that engages in disulfide-dependent interactions in the
      endoplasmic reticulum.
AB  - Protein disulfide isomerase (PDI) is the archetypal enzyme involved in the
      formation and reshuffling of disulfide bonds in the endoplasmic reticulum (ER).
      PDI achieves its redox function through two highly conserved thioredoxin domains,
      and PDI can also operate as an ER chaperone. The substrate specificities and the
      exact functions of most other PDI family proteins remain important unsolved
      questions in biology. Here, we characterize a new and striking member of the PDI
      family, which we have named protein disulfide isomerase-like protein of the
      testis (PDILT). PDILT is the first eukaryotic SXXC protein to be characterized in
      the ER. Our experiments have unveiled a novel, glycosylated PDI-like protein
      whose tissue-specific expression and unusual motifs have implications for the
      evolution, catalytic function, and substrate selection of thioredoxin family
      proteins. We show that PDILT is an ER resident glycoprotein that liaises with
      partner proteins in disulfide-dependent complexes within the testis. PDILT
      interacts with the oxidoreductase Ero1alpha, demonstrating that the N-terminal
      cysteine of the CXXC sequence is not required for binding of PDI family proteins
      to ER oxidoreductases. The expression of PDILT, in addition to PDI in the testis,
      suggests that PDILT performs a specialized chaperone function in testicular
      cells. PDILT is an unusual PDI relative that highlights the adaptability of
      chaperone and redox function in enzymes of the endoplasmic reticulum.

PMID- 15475358
TI  - Arginine 391 in subunit I of the cytochrome bd quinol oxidase from Escherichia
      coli stabilizes the reduced form of the hemes and is essential for quinol oxidase
      activity.
AB  - The cytochrome bd quinol oxidase is one of two respiratory oxidases in
      Escherichia coli. It oxidizes dihydroubiquinol or dihydromenaquinol while
      reducing dioxygen to water. The bd-type oxidases have only been found in
      prokaryotes and have been implicated in the survival of some bacteria, including
      pathogens, under conditions of low aeration. With a high affinity for dioxygen,
      cytochrome bd not only couples respiration to the generation of a proton motive
      force but also scavenges O(2). In the current work, the role of a highly
      conserved arginine residue is explored by site-directed mutagenesis. Four
      mutations were made: R391A, R391K, R391M, and R391Q. All of the mutations except
      R391K result in enzyme lacking ubiquinol oxidase activity. Oxidase activity using
      the artificial reductant N,N,N',N'-tetramethyl-p-phenylenediamine in place of
      ubiquinol was, however, unimpaired by the mutations, indicating that the
      catalytic center where O(2) is reduced is intact. UV-visible spectra of each of
      the mutant oxidases show no perturbations to any of the three heme components
      (heme b(558), heme b(595), and heme d). However, spectroelectrochemical
      titrations of the R391A mutant reveal that the midpoint potentials of all of the
      heme components are substantially lower compared with the wild type enzyme. Since
      Arg(391) is close to Met(393), one of the axial ligands to heme b(558), it is to
      be expected that the R391A mutation might destabilize the reduced form of heme
      b(558). The fact that the midpoint potentials of heme d and heme b(595) are also
      significantly lowered in the R391A mutant is consistent with these hemes being
      physically close together on the periplasmic side of the membrane.

PMID- 15475359
TI  - Lens epithelium-derived growth factor/p75 prevents proteasomal degradation of HIV
      1 integrase.
AB  - The transcriptional coactivator lens epithelium-derived growth factor (LEDGF)/p75
      acts as a chromatin tethering factor for human immunodeficiency virus type 1 (HIV
      1) integrase protein, determining its nuclear localization and its tight
      association with nuclear DNA. Here we identify a second function for the
      LEDGF/p75-integrase interaction. We observed that stable introduction of HIV-1
      integrase (IN) transcription units into cells made stringently LEDGF/p75
      deficient by RNAi resulted in much lower steady state levels of IN protein than
      introduction into LEDGF/p75 wild type cells. The same LEDGF/p75-dependent
      disparity was observed for feline immunodeficiency virus IN. However, IN mRNA
      levels were equivalent in the presence and absence of LEDGF/p75. A post
      translational mechanism was confirmed when the half-life of HIV-1 IN protein was
      found to be much shorter in LEDGF/p75-deficient cells. Proteasome inhibition
      fully countered this extreme instability, increasing IN protein levels to those
      seen in LEDGF/p75 wild type cells and implicating proteasomal destruction as the
      main cause of IN instability. Consistent with these data, increased ubiquitinated
      HIV-1 IN was found in the LEDGF/p75 knock-down cells. Moreover, restoration of
      LEDGF/p75 to knocked down clones rescued HIV-1 IN stability. Subcellular
      fractionation showed that HIV-1 IN is exclusively cytoplasmic in LEDGF/p75
      deficient cells, but mainly nuclear in LEDGF/p75 wild type cells, and that
      cytoplasmic HIV-1 IN has a shorter half-life than nuclear HIV-1 IN. However,
      using LEDGF proteins defective for nuclear localization and IN interaction, we
      further determined that protection of HIV-1 IN from the proteasome requires
      neither chromatin tethering nor nuclear residence. Protection requires only
      interaction with LEDGF/p75, and it is independent of the subcellular localization
      of the IN-LEDGF complex.

PMID- 15475360
TI  - Reconstitution and analysis of soluble inhibin and activin receptor complexes in
      a cell-free system.
AB  - Activins and inhibins compose a heterogeneous subfamily within the transforming
      growth factor-beta (TGF-beta) superfamily of growth and differentiation factors
      with critical biological activities in embryos and adults. They signal through a
      heteromeric complex of type II, type I, and for inhibin, type III receptors. To
      characterize the affinity, specificity, and activity of these receptors (alone
      and in combination) for the inhibin/activin subfamily, we developed a cell-free
      assay system using soluble receptor-Fc fusion proteins. The soluble activin type
      II receptor (sActRII)-Fc fusion protein had a 7-fold higher affinity for activin
      A compared with sActRIIB-Fc, whereas both receptors had a marked preference for
      activin A over activin B. Although inhibin A and B binding was 20-fold lower
      compared with activin binding to either type II receptor alone, the mixture of
      either type II receptor with soluble TGF-beta type III receptor (TbetaRIII;
      betaglycan)-Fc reconstituted a soluble high affinity inhibin receptor. In
      contrast, mixing either soluble activin type II receptor with soluble activin
      type I receptors did not substantially enhance activin binding. Our results
      support a cooperative model of binding for the inhibin receptor
      (ActRII.sTbetaRIII complex) but not for activin receptors (type II + type I) and
      demonstrate that a complex composed of activin type II receptors and TbetaRIII is
      both necessary and sufficient for high affinity inhibin binding. This study also
      illustrates the utility of this cell-free system for investigating hypotheses of
      receptor complex mechanisms resulting from crystal structure analyses.

PMID- 15475361
TI  - Mechanism of membrane binding of the phospholipase D1 PX domain.
AB  - Mammalian phospholipases D (PLD), which catalyze the hydrolysis of
      phosphatidylcholine to phosphatidic acid (PA), have been implicated in various
      cell signaling and vesicle trafficking processes. Mammalian PLD1 contains two
      different membrane-targeting domains, pleckstrin homology and Phox homology (PX)
      domains, but the precise roles of these domains in the membrane binding and
      activation of PLD1 are still unclear. To elucidate the role of the PX domain in
      PLD1 activation, we constructed a structural model of the PX domain by homology
      modeling and measured the membrane binding of this domain and selected mutants by
      surface plasmon resonance analysis. The PLD1 PX domain was found to have high
      phosphoinositide specificity, i.e. phosphatidylinositol 3,4,5-trisphosphate
      (PtdIns-(3,4,5)P(3)) >> phosphatidylinositol 3-phosphate > phosphatidylinositol 5
      phosphate >> other phosphoinositides. The PtdIns(3,4,5)P(3) binding was
      facilitated by the cationic residues (Lys(119), Lys(121), and Arg(179)) in the
      putative binding pocket. Consistent with the model structure that suggests the
      presence of a second lipid-binding pocket, vesicle binding studies indicated that
      the PLD1 PX domain could also bind with moderate affinity to PA,
      phosphatidylserine, and other anionic lipids, which were mediated by a cluster of
      cationic residues in the secondary binding site. Simultaneous occupancy of both
      binding pockets synergistically increases membrane affinity of the PX domain.
      Electrostatic potential calculations suggest that a highly positive potential
      near the secondary binding site may facilitate the initial adsorption of the
      domain to the anionic membrane, which is followed by the binding of
      PtdIns(3,4,5)P(3) to its binding pocket. Collectively, our results suggest that
      the interaction of the PLD1 PX domain with PtdIns(3,4,5)P(3) and/or PA (or
      phosphatidylserine) may be an important factor in the spatiotemporal regulation
      and activation of PLD1.

PMID- 15475362
TI  - Ca2+-induced reactive oxygen species production promotes cytochrome c release
      from rat liver mitochondria via mitochondrial permeability transition (MPT)
      dependent and MPT-independent mechanisms: role of cardiolipin.
AB  - Release of cytochrome c from mitochondria is considered a critical, early event
      in the induction of an apoptosis cascade that ultimately leads to programmed cell
      death. Mitochondrial Ca(2+) loading is a trigger for the release of cytochrome c,
      although the molecular mechanism underlying this effect is not fully clarified.
      This study tested the hypothesis that distinct Ca(2+) thresholds may induce
      cytochrome c release from rat liver mitochondria by membrane permeability
      transition (MPT)-dependent and independent mechanisms. The involvement of
      reactive oxygen species (ROS) and cardiolipin in the Ca(2+)-induced cytochrome c
      release was also investigated. Cytochrome c was quantitated by a new, very
      sensitive, and rapid reverse-phase high performance liquid chromatography method
      with a detection limit of 0.1 pmol/sample. We found that a low extramitochondrial
      Ca(2+) level (2 microM) promoted the release of approximately 13% of the total
      alamethicin releasable pool of cytochrome c from mitochondria. This release was
      not depending of MPT; it was mediated by Ca(2+)-induced ROS production and
      cardiolipin peroxidation and appears to involve the voltage-dependent anion
      channel. High extramitochondrial Ca(2+) level (20 microM) promoted approximately
      45% of the total releasable pool of cytochrome c. This process was MPT-dependent
      and was also mediated by ROS and cardiolipin. It is suggested that distinct
      Ca(2+) levels may determine the mode and the amount of cytochrome c release from
      rat liver mitochondria. The data may help to clarify the molecular mechanism
      underlying the Ca(2+)-induced release of cytochrome c from rat liver mitochondria
      and the role played by ROS and cardiolipin in this process.

PMID- 15475364
TI  - Release factors eRF1 and RF2: a universal mechanism controls the large
      conformational changes.
AB  - Class I release factors 1 and 2 (RF1 and RF2) terminate protein synthesis by
      recognizing stop codons on the mRNA via their conserved amino acid motifs (NIKS
      in eRF1 and SPF in RF2) and by the conserved tripeptide (GGQ) interactions with
      the ribosomal peptidyltransferase center. Crystal structures of eRF1 and RF2 do
      not fit their ribosomal binding pocket (approximately 73 angstroms). Cryoelectron
      microscopy indicates large conformational changes in the ribosome-bound RF2.
      Here, we investigate the conformational dynamics of the eRF1 and RF2 using
      molecular dynamics simulation, structural alignment, and electrostatic analysis
      of domain interactions. We show that relaxed eRF1 has a shape remarkably similar
      to the ribosome-bound RF2 observed by cryoelectron microscopy. The similarity
      between the two release factors is as good as between elongation factor G and
      elongation factor Tu-guanosine-5'(beta,gamma-imido)triphosphate-tRNA. Further,
      the conformational transitions and dynamics of eRF1 and RF2 between the free and
      ribosome-bound states are most likely controlled by protonation of conserved
      histidines. For eRF1, the distance between the NIKS and GGQ motifs shrinks from
      97.5 angstroms in the crystal to 70-80 angstroms. For RF2, the separation between
      SPF and GGQ elongates from 32 angstroms in the crystal to 50 angstroms. Coulombic
      interaction strongly favors the open conformation of eRF1; however, solvation and
      histidine protonation modulate the domain interactions, making the closed
      conformation of eRF1 more accessible. Thus, RF1 and RF2 function like molecular
      machines, most likely fueled by histidine protonation. The unified conformational
      control and the shapes of eRF1 and RF2 support the proposition that the
      termination of protein synthesis involves similar mechanisms across species.

PMID- 15475363
TI  - Cytosolic phospholipase A2-alpha is necessary for platelet-activating factor
      biosynthesis, efficient neutrophil-mediated bacterial killing, and the innate
      immune response to pulmonary infection: cPLA2-alpha does not regulate neutrophil
      NADPH oxidase activity.
AB  - The role of a cytosolic phospholipase A(2)-alpha (cPLA(2)-alpha) in neutrophil
      arachidonic acid release, platelet-activating factor (PAF) biosynthesis, NADPH
      oxidase activation, and bacterial killing in vitro, and the innate immune
      response to bacterial infection in vivo was examined. cPLA(2)-alpha activity was
      blocked with the specific cPLA(2)-alpha inhibitor, Pyrrolidine-1 (human cells),
      or by cPLA(2) -alpha gene disruption (mice). cPLA(2)-alpha inhibition or gene
      disruption led to complete suppression of neutrophil arachidonate release and PAF
      biosynthesis but had no effect on neutrophil NADPH oxidase activation,
      FcgammaII/III or CD11b surface expression, primary or secondary granule
      secretion, or phagocytosis of Escherichia coli in vitro. In contrast, cPLA(2)
      alpha inhibition or gene disruption diminished neutrophil-mediated E. coli
      killing in vitro, which was partially rescued by exogenous arachidonic acid or
      PAF but not leukotriene B(4). Following intratracheal inoculation with live E.
      coli in vivo, pulmonary PAF biosynthesis, inflammatory cell infiltration, and
      clearance of E. coli were attenuated in cPLA(2)-alpha(-/-) mice compared with
      wild type littermates. These studies identify a novel role for cPLA(2)-alpha in
      the regulation of neutrophil-mediated bacterial killing and the innate immune
      response to bacterial infection.

PMID- 15475365
TI  - A 50-A separation of the integrin alpha v beta 3 extracellular domain C termini
      reveals an intermediate activation state.
AB  - The integrin alpha(v)beta(3) has been shown to exist in low and high affinity
      conformations. Activation to the high affinity state is thought to depend on the
      "switchblade-like" opening, from a low affinity bent conformation with a closed
      headpiece to an extended form of the integrin with an open headpiece. Activation
      has been shown to depend on separation of the cytoplasmic domains. How
      cytoplasmic domain separation is related to separation of the transmembrane
      domains is unknown, and the distance of separation of the transmembrane domains
      required for activation has not been defined. A constrained secreted form of
      alpha(v)beta(3) was engineered that introduced a 50-A separation of the integrin
      C-terminal tails of the extracellular domains of the alpha(v) and beta(3)
      subunits. Receptor binding and recognition by ligand-induced binding state (LIBS)
      monoclonal antibodies demonstrated that the mutant receptor was locked into a low
      affinity state that was likely in a partially extended conformation but with a
      closed headpiece. In the presence of RGD peptide, the constrained receptor was
      able to fully extend, as determined by full exposure of LIBS epitopes. In the
      presence of the appropriate LIBS antibody, high affinity ligand binding of the
      constrained receptor was achieved. The results support the existence of transient
      intermediate activation states of secreted alpha(v)beta(3). Furthermore, these
      results with the secreted alpha(v)beta(3) receptor support a model for the full
      length membrane-bound form of alpha(v)beta(3), whereby a 50-A lateral separation
      of the integrin alpha(v) and beta(3) transmembrane domains would be sufficient to
      enforce the switchblade-like opening to the extended conformation but
      insufficient for full receptor activation.

PMID- 15475366
TI  - Phorbol ester treatment of K562 cells regulates the transcriptional activity of
      AML1c through phosphorylation.
AB  - We find that phorbol ester (PE) treatment of K562 cells greatly stimulates
      promoters (T cell receptor beta, myeloperoxidase, macrophage colony-stimulating
      factor receptor, and granulocyte macrophage colony-stimulating factor receptor)
      containing AML1 transcription factor binding sites. This stimulation of AML1c
      transcriptional activity is mediated by direct phosphorylation of the AML1c
      molecule on multiple phosphorylation sites. Eleven AML1c (S/T)P sites in the
      transcriptional activating domain are phosphorylated at a basal level in
      untreated K562 cells; treatment of the K562 cells with PE results in increased
      phosphorylation at five of these sites (serines 276, 293, 303, 462, and threonine
      300). Mutation of these five sites to alanine inhibits PE-induced transcriptional
      activity; mutation of the sites to an acidic amino acid, aspartic acid,
      stimulates constitutive activity. Single mutations in four amino acids or double
      mutations (serines 276 and 293 or threonine 300 and serine 303) have little
      effect on AML1c transcriptional activity. Inhibitor assays suggest that the ERK
      family of protein kinases is activated by PEs to phosphorylate the (S/T)P sites
      within the AML1c molecule and markedly enhance the transcriptional activity of
      AML1c.

PMID- 15475367
TI  - Caspase-2 permeabilizes the outer mitochondrial membrane and disrupts the binding
      of cytochrome c to anionic phospholipids.
AB  - Caspases are cysteine proteases that play a central role in the execution of
      apoptosis. Recent evidence indicates that caspase-2 is activated early in
      response to genotoxic stress and can function as an upstream modulator of the
      mitochondrial apoptotic pathway. In particular, we have shown previously that
      fully processed caspase-2 can permeabilize the outer mitochondrial membrane and
      cause cytochrome c and Smac/DIABLO release from these organelles. Using
      permeabilized cells, isolated mitochondria, and protein-free liposomes, we now
      report that this effect is direct and depends neither on the presence or cleavage
      of other proteins nor on a specific phospholipid composition of the liposomal
      membrane. Interestingly, caspase-2 was also shown to disrupt the interaction of
      cytochrome c with anionic phospholipids, notably cardiolipin, and thereby enhance
      the release of the hemoprotein caused by treatment of mitochondria with digitonin
      or the proapoptotic protein Bax. Combined, our data suggest that caspase-2
      possesses an unparalleled ability to engage the mitochondrial apoptotic pathway
      by permeabilizing the outer mitochondrial membrane and/or by breaching the
      association of cytochrome c with the inner mitochondrial membrane.

PMID- 15475369
TI  - Sensitization of cells to TRAIL-induced apoptosis by decoy receptor 3.
AB  - Decoy receptor 3 (DcR3)/TR6/M68 is a soluble receptor that binds to the Fas
      ligand LIGHT and TL1A. Elevated levels of DcR3 expression have been found in many
      tumors. We report an unexpected effect of DcR3 by sensitizing Jurkat and U937
      cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL). Cell death triggered by anti-Fas and tumor necrosis factor was
      unaffected by DcR3. DcR3 by itself did not stimulate apoptosis. The ability to
      augment TRAIL-initiated cell death was not observed with soluble lymphotoxin beta
      receptor or soluble death receptor 3, indicating that binding to LIGHT or TL1A
      alone is insufficient to trigger TRAIL sensitivity. Incubation with DcR3 did not
      increase the surface expression of TRAIL receptor, and the level of Fas
      associated death domain protein and cellular FLICE-like inhibitory protein was
      not altered. Instead, in the presence of DcR3, TRAIL engagement resulted in an
      increased activation of caspase-8, an elevated cleavage of Bid, and enhanced
      release of Smac and cytochrome c from mitochondria to cytosol compared with TRAIL
      alone. This led to increased activation of caspase-9 and caspase-3. The unusual
      ability of DcR3 to promote TRAIL-triggered death may be used to potentiate TRAIL
      efficacy during treatment tumors overexpressing DcR3.

PMID- 15475368
TI  - Hydroperoxy fatty acid cycling mediated by mitochondrial uncoupling protein UCP2.
AB  - Functional activation of mitochondrial uncoupling protein-2 (UCP2) is proposed to
      decrease reactive oxygen species production. Skulachev and Goglia (Skulachev, V.
      P., and Goglia, F. (2003) FASEB J. 17, 1585-1591) hypothesized that hydroperoxy
      fatty acid anions are translocated by UCPs but cannot flip-flop across the
      membrane. We found that the second aspect is otherwise; the addition of
      synthesized linoleic acid hydroperoxides (LAOOH, a mix of four isomers) caused a
      fast flip-flop-dependent acidification of liposomes, comparable with the linoleic
      acid (LA)-dependent acidification. Using Escherichia coli-expressed UCP2
      reconstituted into liposomes we found that LAOOH induced purine nucleotide
      sensitive H(+) uniport in UCP2-proteoliposomes with higher affinity than LA (K(m)
      values 97 microM for LAOOH and 275 microM for LA). In UCP2-proteoliposomes LAOOH
      also induced purine nucleotide-sensitive K(+) influx balanced by anionic charge
      transfer, indicating that LAOOH was also transported as an anion with higher
      affinity than linoleate anion, the K(m) values being 90 and 350 microM,
      respectively. These data suggest that hydroperoxy fatty acids are transported via
      UCP2 by a fatty acid cycling mechanism. This may alternatively explain the
      observed activation of UCP2 by the externally generated superoxide. The ability
      of LAOOH to induce UCP2-mediated H(+) uniport points to the essential role of
      superoxide reaction products, such as hydroperoxyl radical, hydroxyl radical, or
      peroxynitrite, initiating lipoperoxidation, the released products of which
      support the UCP2-mediated uncoupling and promote the feedback down-regulation of
      mitochondrial reactive oxygen species production.

PMID- 15475370
TI  - Stromal cell-derived factor-1 (SDF-1) signalling regulates human placental
      trophoblast cell survival.
AB  - Stromal cell-derived factor-1 (SDF-1 or CXCL12) is the physiologic ligand for the
      chemokine receptor CXCR4. CXCR4-mediated signalling regulates cell migration and
      apoptosis in certain haematopoietic and neuronal cells. Using gene profiling, we
      determined that CXCR4 is the only chemokine receptor for which mRNA expression is
      regulated during trophoblast differentiation in vitro. Based on the known effects
      of CXCR4 ligation, we hypothesized that CXCR4 activation may regulate placental
      trophoblast cell survival (i.e. protection from apoptosis), an important
      mechanism for the establishment and maintenance of the uteroplacental barrier.
      Human cytotrophoblasts (CTBs) were cultured in defined media and treated with
      graded doses of SDF-1 (10-100 ng/ml) or with an anti-CXCR4 neutralizing antibody.
      Exposure to anti-CXCR4 antibody reduced CTB cell numbers by 25-40%. Treatment
      with SDF-1 decreased the proportions of apoptotic terminal deoxynucleotidyl
      transferase-mediated dUTP-FITC nick-end labelling(+) cells (apoptotic index [AI]
      of 2.79+/-0.61% [control] versus 1.88+/-0.56% [SDF-1]; P<0.05) and caspase
      activated cells (AI of 7.95+/-2.49% [control] versus 3.81+/-1.49% [SDF-1];
      P<0.05). We determined that SDF-1 also activated the triple MAP Kinase isoforms
      ERK1/2 and p38 in trophoblasts. Immunocytochemistry confirmed SDF-1-induced
      nuclear translocation of phosphorylated ERK1/2. Blocking of ERK1/2 signalling
      with the specific inhibitor PD98059 reversed SDF-1-mediated inhibition of
      apoptosis (AI of 1.65+/-0.34 [SDF-1] versus 3.50+/-0.5 [SDF-1 + PD98059];
      P<0.05), suggesting that SDF-1 acts through this pathway as a trophoblast
      survival factor. These results indicate that SDF-1/CXCR4 signalling stimulates
      anti-apoptotic pathways in cultured trophoblasts. This chemotactic
      ligand/receptor system may promote trophoblast survival during pregnancy.
      Alterations in SDF-1 and/or CXCR4 expression or function may be associated with
      specific pregnancy disorders.

PMID- 15475371
TI  - Functional characterization of somatic point mutations of the human estrogen
      receptor alpha (hERalpha) in adenomyosis uteri.
AB  - Endometriosis and adenomyosis uteri are chronic, benign diseases caused by the
      presence of endometrial tissue in ectopic locations, e.g. peritoneal or deep
      inside the myometrial wall of the uterus and/or in the rectovaginal septum.
      Although adenomyosis might be considered as a special form of endometriosis, both
      conditions differ with respect to clinical symptoms and treatment. Induction of a
      hypo-estrogenic state alone or in combination with surgical removal of the extra
      uterine lesion is mostly sufficient for treatment of peritoneal endometriosis. By
      contrast, adenomyosis uteri rarely responds to hormonal therapy and usually
      requires a hysterectomy for cure. Consequently, the role of steroid hormone
      receptors with respect to the aetiology of either condition is still a matter of
      discussion. Using PCR/single strand conformation polymorphism analysis, we
      identified somatic estrogen receptor (ER) alpha gene mutations in three out of 55
      samples from adenomyosis uteri. Functional characterization revealed that two of
      the mutant ERalpha proteins display severely impaired DNA-binding and
      transactivation properties secondary to an altered response to estrogens or
      changes in epidermal growth factor-mediated ligand-independent activation.
      Although the exact mechanism remains unknown, we suggest that mutation-related
      silencing of estrogen responsiveness might render endometriotic cells resistant
      to hypo-estrogenic conditions thereby accounting for failure of estrogen-ablative
      therapy in adenomyosis.

PMID- 15475372
TI  - Increases in DNA fragmentation and induction of a senescence-specific nuclease
      are delayed during corolla senescence in ethylene-insensitive (etr1-1) transgenic
      petunias.
AB  - The programmed senescence of flower petals has been shown to involve the
      fragmentation of nuclear DNA. Nuclear DNA fragmentation, as determined by the
      TUNEL assay, was detected in Petunia x hybrida corollas during both pollination
      induced and age-related senescence. DNA fragmentation was detected late in the
      lifespan of the flower when corollas were wilting and producing ethylene. The
      induction of a 43 kDa nuclease (PhNUC1) correlated with increased DNA
      fragmentation. PhNUC1 is a glycoprotein with activity against DNA and RNA and a
      pH optimum of 7.5. EDTA was found to inhibit PhNUC1 activity, but the addition of
      Co2+ restored activity in the presence of the chelating agent. When total protein
      extracts from senescing petals were fractionated by differential centrifugation,
      PhNUC1 activity was detected in the nuclear but not the cytoplasmic fraction.
      Activity of PhNUC1 was induced in non-senescing corollas by treatment with
      ethylene. Delayed increases in PhNUC1 activity observed in ethylene-insensitive
      flowers (35S:etr1-1) suggest that ethylene modulates the timing of PhNUC1
      induction, but that it is not an absolute requirement for its activation.

PMID- 15475373
TI  - Breeding for high water-use efficiency.
AB  - There is a pressing need to improve the water-use efficiency of rain-fed and
      irrigated crop production. Breeding crop varieties with higher water-use
      efficiency is seen as providing part of the solution. Three key processes can be
      exploited in breeding for high water-use efficiency: (i) moving more of the
      available water through the crop rather than it being wasted as evaporation from
      the soil surface or drainage beyond the root zone or being left behind in the
      root zone at harvest; (ii) acquiring more carbon (biomass) in exchange for the
      water transpired by the crop, i.e. improving crop transpiration efficiency; (iii)
      partitioning more of the achieved biomass into the harvested product. The
      relative importance of any one of these processes will vary depending on how
      water availability varies during the crop cycle. However, these three processes
      are not independent. Targeting specific traits to improve one process may have
      detrimental effects on the other two, but there may also be positive
      interactions. Progress in breeding for improved water-use efficiency of rain-fed
      wheat is reviewed to illustrate the nature of some of these interactions and to
      highlight opportunities that may be exploited in other crops as well as potential
      pitfalls. For C3 species, measuring carbon isotope discrimination provides a
      powerful means of improving water-use efficiency of leaf gas exchange, but
      experience has shown that improvements in leaf-level water-use efficiency may not
      always translate into higher crop water-use efficiency or yield. In fact, the
      reverse has frequently been observed. Reasons for this are explored in some
      detail. Crop simulation modelling can be used to assess the likely impact on
      water-use efficiency and yield of changing the expression of traits of interest.
      Results of such simulations indicate that greater progress may be achieved by
      pyramiding traits so that potential negative effects of individual traits are
      neutralized. DNA-based selection techniques may assist in such a strategy.

PMID- 15475374
TI  - Bcl-2 family members localize to tobacco chloroplasts and inhibit programmed cell
      death induced by chloroplast-targeted herbicides.
AB  - In mammalian cells, apoptosis is often mediated via organelles. While apoptotic
      like cell death occurs in plants, the mechanistic details are unresolved.
      Transgenic tobacco plants have been generated that harbour selected animal anti
      apoptotic genes. Subcellular fractionation followed by western blot analysis
      indicated that chloroplasts serve as a location for these animal anti-apoptotic
      proteins in addition to the established mitochondrial location. To explore the
      functional significance of this observation, tobacco plants were treated with
      three chloroplast-directed herbicides. Wild-type plants died and exhibited
      features associated with apoptosis. Transgenic plants survived and did not show
      any apoptotic-like characteristics. Moreover, the herbicide-induced apoptotic
      like cell death was light requiring. It was concluded that chloroplasts may be
      involved in mediating certain types of plant programmed cell death.

PMID- 15475375
TI  - Maize cytokinin oxidase genes: differential expression and cloning of two new
      cDNAs.
AB  - Cytokinin oxidases (CKOs) play a major role in the regulation of hormone levels
      in plants by irreversibly degrading cytokinins. Two new cDNAs from maize (CKO2
      and CKO3) were cloned and CKO activity of a recombinant CKO3 enzyme was
      demonstrated. CKO2 and CKO3 encode flavoproteins with 93% identity among each
      other compared with 45% identity with CKO1. The respective genes were mapped to
      BIN 3.05/06 and BIN 8.06 which belong to duplicated regions of the maize genome.
      For a better understanding of the role of CKO2 and CKO3 in maize development,
      their expression profiles were analysed in different organs and during kernel
      development via semi-quantitative RT-PCR. Different spatial and temporal
      expression patterns were observed for the two genes, as well as for CKO1 and two
      additional genes CKO4 and CKO5. CKO2 to CKO5 genes were mainly expressed in
      vegetative tissues, with unique expression patterns. CKO1 was most strongly
      expressed in the kernel. All five genes were expressed at early stages of kernel
      development, a period when a peak in cytokinin levels and a high cell division
      rate in the endosperm have been described. However, each gene had its own
      expression profile with a major difference concerning the onset of expression.

PMID- 15475376
TI  - The early light-inducible protein (ELIP) gene is expressed during the chloroplast
      to-chromoplast transition in ripening tomato fruit.
AB  - Chloroplast-to-chromoplast transitions during fruit ripening require massive
      transformation of the plastid internal membrane structure as the photosynthetic
      apparatus is disassembled. Early Light-Inducible Proteins (ELIPs) are known to
      accumulate in chloroplasts during thylakoid biogenesis and under stressful
      conditions. To determine if ELIP may also play a role in thylakoid disassembly
      during the chloroplast-to-chromoplast transition, ELIP mRNA expression was
      measured in tomato, Lycopersicon esculentum Mill. cv. Rutgers. An EST clone was
      identified in the Tomato Genome Project/Solanaceae Genomics Network database that
      has high sequence similarity with the amino acid sequence of Arabidopsis ELIP1
      and ELIP2. It has complete identity in the two conserved regions of the protein.
      Genomic Southern blots indicate that the gene is a single copy in tomato. The
      genomic sequence shows the three-exon structure typical of ELIP sequences from
      other species. mRNA for this gene is barely detectable on northern blots from
      etiolated seedlings, but transiently accumulates to high levels 2 h after
      transfer to the light. Greenhouse-grown tomatoes were used to measure ELIP mRNA
      accumulation during fruit development and ripening. Tomato ELIP mRNA is
      detectable in all stages of fruit ripening, but is most abundant in the
      breaker/turning stage of development. A survey of tomato EST databases revealed
      that ELIP cDNA is also relatively abundant in developing flowers, which contain
      yellow chromoplasts. Combined, these results suggest that ELIP may play a newly
      recognized role in the chloroplast-to-chromoplast transition process.

PMID- 15475377
TI  - Mechanisms underlying plant resilience to water deficits: prospects for water
      saving agriculture.
AB  - Drought is one of the greatest limitations to crop expansion outside the present
      day agricultural areas. It will become increasingly important in regions of the
      globe where, in the past, the problem was negligible, due to the recognized
      changes in global climate. Today the concern is with improving cultural practices
      and crop genotypes for drought-prone areas; therefore, understanding the
      mechanisms behind drought resistance and the efficient use of water by the plants
      is fundamental for the achievement of those goals. In this paper, the major
      constraints to carbon assimilation and the metabolic regulations that play a role
      in plant responses to water deficits, acting in isolation or in conjunction with
      other stresses, is reviewed. The effects on carbon assimilation include increased
      resistance to diffusion by stomata and the mesophyll, as well as biochemical and
      photochemical adjustments. Oxidative stress is critical for crops that experience
      drought episodes. The role of detoxifying systems in preventing irreversible
      damage to photosynthetic machinery and of redox molecules as local or systemic
      signals is revised. Plant capacity to avoid or repair membrane damage during
      dehydration and rehydration processes is pivotal for the maintenance of membrane
      integrity, especially for those that embed functional proteins. Among such
      proteins are water transporters, whose role in the regulation of plant water
      status and transport of other metabolites is the subject of intense
      investigation. Long-distance chemical signalling, as an early response to
      drought, started to be unravelled more than a decade ago. The effects of those
      signals on carbon assimilation and partitioning of assimilates between
      reproductive and non-reproductive structures are revised and discussed in the
      context of novel management techniques. These applications are designed to
      combine increased crop water-use efficiency with sustained yield and improved
      quality of the products. Through an understanding of the mechanisms leading to
      successful adaptation to dehydration and rehydration, it has already been
      possible to identify key genes able to alter metabolism and increase plant
      tolerance to drought. An overview of the most important data on this topic,
      including engineering for osmotic adjustment or protection, water transporters,
      and C4 traits is presented in this paper. Emphasis is given to the most
      successful or promising cases of genetic engineering in crops, using functional
      or regulatory genes. as well as to promising technologies, such as the transfer
      of transcription factors.

PMID- 15475378
TI  - Nitrate reductase regulation in tomato roots by exogenous nitrate: a possible
      role in tolerance to long-term root anoxia.
AB  - The mechanism of nitrate reductase (NR) regulation under long-term anoxia in
      roots of whole plants and the putative role of nitrate in anoxia tolerance have
      been addressed. NR activity in tomato roots increased significantly after 24 h of
      anaerobiosis and increased further by 48 h, with a concomitant release of nitrite
      into the culture medium. Anoxia promoted NR activation through dissociation of
      the 14-3-3 protein inhibitor and NR dephosphorylation. After 24 h of anoxia, the
      total amount of NR increased slightly up to 48 h. However, NR-mRNA levels
      remained constant between 0 h and 24 h of root anoxia and decreased after 48 h.
      This is probably due to the inhibition of NR degradation and the accumulation of
      its native form. NR was slightly dephosphorylated in the absence of oxygen and
      nitrate. Under anoxia, NR dephosphorylation was modulated by nitrate-controlled
      NR activity. In addition, the presence of nitrate prevents anoxic symptoms on
      leaves and delays wilting by 48 h during root anoxia. In the absence of nitrate,
      plants withered within 24 h, as they did with tungstate treatment, an inhibitor
      of NR activity. Thus, anoxia tolerance of tomato roots could be enhanced by
      nitrate reduction.

PMID- 15475379
TI  - Changes in the ascorbate metabolism of apoplastic and symplastic spaces are
      associated with cell differentiation.
AB  - Ascorbate levels and redox state, as well as the activities of the ascorbate
      related enzymes, have been analysed both in the apoplastic and symplastic spaces
      of etiolated pea (Pisum sativum L.) shoots during cellular differentiation. The
      ascorbate pool and the ascorbate oxidizing enzymes, namely ascorbate oxidase and
      ascorbate peroxidase, were present in both pea apoplast and symplast, whereas
      ascorbate free radical reductase and dehydroascorbate reductase were only present
      in the symplastic fractions. During cell differentiation the ascorbate redox
      enzymes changed in different ways, since a decrease in ascorbate levels,
      ascorbate peroxidase and ascorbate free radical reductase occurred from
      meristematic to differentiated cells, whereas ascorbate oxidase and
      dehydroascorbate reductase increased. The activity of secretory peroxidases has
      also been followed in the apoplast of meristematic and differentiating cells.
      These peroxidases increased their activity during differentiation. This behaviour
      was accompanied by changes in their isoenzymatic profiles. The analysis of the
      kinetic characteristics of the different peroxidases present in the apoplast
      suggests that the presence of ascorbate and ascorbate peroxidase in the cell wall
      could play a critical role in regulating the wall stiffening process during cell
      differentiation by interfering with the activity of secretory peroxidases.

PMID- 15475380
TI  - Endotoxin-induced lung injury in mice: structural, functional, and biochemical
      responses.
AB  - Acute lung injury is usually a complication of sepsis, and endotoxin treatment of
      mice is a frequently used experimental model. To define this model and to clarify
      pathogenesis of the lung injury, we injected with 1 mg/kg endotoxin ip and
      measured pulmonary function, pulmonary edema, serum concentrations of cytokines
      and growth factors, and lung histology over 48 h. During the first 6 h, tidal
      volume and minute volume increased and respiratory frequency decreased. Serum
      concentrations of cytokines showed three patterns: 10 cytokines peaked at 2 h and
      declined rapidly, two peaked at 6 h and declined, and two had biphasic peaks at 2
      and 24 h. Growth factors increased later and remained elevated longer. Both
      collagen and fibronectin were deposited in the lungs beginning within hours of
      endotoxin and resolving over 48 h. Histologically, lungs showed increased
      cellularity at 6 h with minimal persistent inflammation at 48 h. Lung water
      peaked at 6 h and gradually decreased over 48 h. We conclude that intraperitoneal
      administration of endotoxin to mice causes a transient systemic inflammatory
      response and transient lung injury and dysfunction. The response is characterized
      by successive waves of cytokine release into the circulation, early evidence of
      lung fibrogenesis, and prolonged increases in growth factors that may participate
      in lung repair.

PMID- 15475381
TI  - RhoA and Rho-kinase dependent and independent signals mediate TGF-beta-induced
      pulmonary endothelial cytoskeletal reorganization and permeability.
AB  - Transforming growth factor (TGF)-beta is a potent inflammatory mediator involved
      in acute lung injury. TGF-beta directly increases pulmonary endothelial myosin
      light chain (MLC) phosphorylation, which is associated with increased endothelial
      stress fiber formation, gap formation, and protein permeability, all hallmarks of
      pulmonary endothelial responses during acute lung injury. We performed the
      following experiments in pulmonary endothelial monolayers to determine whether
      RhoA and Rho-kinase mediate these TGF-beta-induced responses. TGF-beta caused the
      sustained activation of RhoA 2 h posttreatment associated with increased MLC
      phosphorylation. Inhibition of either RhoA or Rho-kinase with either C3 exoenzyme
      or Y-27632 blocked MLC phosphorylation. In addition, both C3 and Y-27632
      partially attenuated the maximal TGF-beta-induced increase in permeability but
      did not affect the initial phase of compromised barrier integrity. Inhibition of
      Rho-kinase completely blocked the TGF-beta-induced increase in the content of
      filamentous actin (F-actin) but only partially inhibited TGF-beta-induced changes
      in actin reorganization. To assess the contribution of Rho-kinase in RhoA
      mediated responses independent of additional TGF-beta-induced signals, cells were
      infected with a constitutively active RhoA adenovirus (RhoAQ63L) with or without
      Y-27632. RhoAQ63L increased MLC phosphorylation, F-actin content, and
      permeability. Treatment with Y-27632 blocked these responses, suggesting that Rho
      kinase mediates these RhoA-induced effects. Collectively, these data suggest the
      following: 1) the RhoA/Rho-kinase pathway is an important component of TGF-beta
      induced effects on endothelial MLC phosphorylation, cytoskeletal reorganization,
      and barrier integrity; and 2) additional signaling mechanisms independent of the
      RhoA/Rho-kinase signaling cascade contribute to TGF-beta-induced changes in
      cytoskeletal organization and permeability.

PMID- 15475382
TI  - Regulation of polymorphonuclear leukocyte apoptosis: role of lung endothelium
      epithelium bilayer transmigration.
AB  - Delayed polymorphonuclear leukocyte (PMN) apoptosis exacerbates acute lung
      injury. To reach the alveolar spaces, PMNs must migrate across both pulmonary
      endothelial and epithelial cell layers. We hypothesized that transmigration
      across the endothelium-epithelium bilayer suppresses PMN apoptosis and sought to
      elucidate the underlying mechanisms. PMNs freshly isolated from normal volunteers
      were allowed to migrate across polycarbonate membranes alone or membranes coated
      with a bilayer of human lung endothelial and epithelial cells. After migration
      toward different chemoattractants (IL-8, formyl-Met-Leu-Phe, or leukotriene
      B(4)), PMN apoptosis and caspase activities were assessed by annexin V,
      histology, and enzymatic assays, respectively. Messenger RNA and specific protein
      expression in three receptor ligand-mediated, apoptosis-inducing pathways (Fas,
      TNF-alpha, and TNF-related apoptosis-inducing ligand) were further examined by
      gene array, RT-PCR, flow cytometry, and Western blot analyses. The data
      demonstrated that transbilayer migration suppressed PMN apoptosis, and this
      effect was not chemoattractant type specific. Kinetic analyses further showed
      that the delay of apoptosis was sustained to at least 18 h. Transbilayer
      migration caused significant decreases in caspase (-3, -8, and -9) activities.
      The changes in apoptosis-related gene expression support the survival role of
      transbilayer migration. Furthermore, the reduced apoptosis was correlated with
      downregulation of Fas ligand and TNF receptor 1 expression. Our data reveal that
      migration across a lung endothelium-epithelium bilayer suppresses PMN apoptosis.
      The decreased activity and/or expression of proapoptotic proteins may provide
      possible targets for the regulation of inappropriate delay in PMN apoptosis
      during lung inflammation and injury.

PMID- 15475383
TI  - Protective effect of IL-6 on alveolar epithelial cell death induced by hydrogen
      peroxide.
AB  - The goal of this study was to examine whether IL-6 could directly protect lung
      resident cells, especially alveolar epithelial cells, from reactive oxygen
      species (ROS)-induced cell death. ROS induced IL-6 gene expression in organotypic
      lung slices of wild-type (WT) mice. ROS also induced IL-6 gene expression in
      mouse primary lung fibroblasts, dose dependently. The organotypic lung slices of
      WT were more resistant to ROS-induced DNA fragmentation than those of IL-6
      deficient (IL-6-/-) mice. WT resistance against ROS was abrogated by treatment
      with anti-IL-6 antibody. TdT-mediated dUTP nick end labeling stain and electron
      microscopy revealed that DNA fragmented cells in the IL-6-/- slice included
      alveolar epithelial cells and endothelial cells. In vitro studies demonstrated
      that IL-6 reduced ROS-induced A549 alveolar epithelial cell death. Together,
      these data suggest that IL-6 played an antioxidant role in the lung by protecting
      lung resident cells, especially alveolar epithelial cells, from ROS-induced cell
      death.

PMID- 15475384
TI  - Gold nanoparticle probe-based gene expression analysis with unamplified total
      human RNA.
AB  - Microarray-based gene expression analysis plays a pivotal role in modern biology
      and is poised to enter the field of molecular diagnostics. Current microarray
      based gene expression systems typically require enzymatic conversion of mRNA into
      labeled cDNA or cRNA. Conversion to cRNA involves a target amplification step
      that overcomes the low sensitivity associated with commonly used fluorescent
      detection methods. Herein, we present a novel enzyme-free, microarray-based gene
      expression system that uses unamplified total human RNA sample as the target
      nucleic acid. The detection of microarray-bound RNA molecules is accomplished by
      targeting the poly-A tail with an oligo-dT20 modified gold nanoparticle probe,
      signal amplification by autometallography, and subsequent measurement of
      nanoparticle-mediated light scattering. The high sensitivity afforded by the
      nanoparticle probes allows differential gene expression from as little as 0.5
      microg unamplified total human RNA in a 2 h hybridization without the need for
      elaborate sample labeling steps.

PMID- 15475385
TI  - KpnBI is the prototype of a new family (IE) of bacterial type I restriction
      modification system.
AB  - KpnBI is a restriction-modification (R-M) system recognized in the GM236 strain
      of Klebsiella pneumoniae. Here, the KpnBI modification genes were cloned into a
      plasmid using a modification expression screening method. The modification genes
      that consist of both hsdM (2631 bp) and hsdS (1344 bp) genes were identified on
      an 8.2 kb EcoRI chromosomal fragment. These two genes overlap by one base and
      share the same promoter located upstream of the hsdM gene. Using recently
      developed plasmid R-M tests and a computer program RM Search, the DNA recognition
      sequence for the KpnBI enzymes was identified as a new 8 nt sequence containing
      one degenerate base with a 6 nt spacer, CAAANNNNNNRTCA. From Dam methylation and
      HindIII sensitivity tests, the methylation loci were predicted to be the
      italicized third adenine in the 5' specific region and the adenine opposite the
      italicized thymine in the 3' specific region. Combined with previous sequence
      data for hsdR, we concluded that the KpnBI system is a typical type I R-M system.
      The deduced amino acid sequences of the three subunits of the KpnBI system show
      only limited homologies (25 to 33% identity) at best, to the four previously
      categorized type I families (IA, IB, IC, and ID). Furthermore, their identity
      scores to other uncharacterized putative genome type I sequences were 53% at
      maximum. Therefore, we propose that KpnBI is the prototype of a new 'type IE'
      family.

PMID- 15475386
TI  - Joining of long double-stranded RNA molecules through controlled overhangs.
AB  - We describe two methods for creating long (>1 kb) dsRNA molecules with specific,
      user-controlled overhangs for efficient hybridization and ligation. The two
      methods create double-stranded RNA (dsRNA) molecules with 5' overhangs or with 3'
      overhangs using T7 RNA polymerase (T7 RNAP) in transcription reactions of
      carefully designed PCR products. Primers utilized in the PCR reactions provide
      the template for the desired dsRNA overhangs. These methods provide complete
      control of the length and the sequence of the overhangs. This supplies a tool
      which is particularly lacking in dsRNA biochemistry given the absence of
      restriction endonucleases active on these substrates.

PMID- 15475388
TI  - A novel Nudix hydrolase for oxidized purine nucleoside triphosphates encoded by
      ORFYLR151c (PCD1 gene) in Saccharomyces cerevisiae.
AB  - A search for candidates for a functional homologue of Escherichia coli MutT in
      yeast Saccharomyces cerevisiae was made in the NCBI-BLAST database using the
      Nudix box, a short amino acid sequence conserved among E.coli MutT, Pseudomonoas
      vulgaris MutT, and human, rat and mouse MTH1. Among five candidates, we focused
      on the open reading frame YLR151c, because it had a region with approximately 76%
      similarity to the N-terminal half of MutT including the Nudix box. We thus
      evaluated the ability of YLR151c as a functional homologue of E.coli MutT in
      S.cerevisiae. Expression of YLR151c was able to suppress the transversion from
      A:T to C:G caused by misincorporation of the oxidized nucleotide 8-oxo-dGTP in
      the E.coli mutT-deficient strain. The disruption of the YLR151c in yeast strain
      caused approximately 14-fold increase in the frequency of spontaneous mutation
      compared to the wild type. Additionally, biochemical analysis indicated that GST
      YLR151c fusion protein possessed pyrophosphatase activity for both 7,8-dihydro-8
      oxo-2'-deoxyguanosine triphosphate (8-oxo-dGTP) and 1,2-dihydro-2-hydroxy-2'
      deoxyadenosine triphosphate (2-OH-dATP). The specific activity of GST-YLR151c for
      8-oxo-dGTP was 5.6 x 10(-3) microM(-1) s(-1), which was similar to that of RibA,
      a backup enzyme for MutT in E.coli, but was 150-fold lower than that of hMTH1.
      From these results, we conclude that YLR151c has an ability to prevent
      spontaneous mutagenesis via sanitization of oxidized nucleotides, and that it may
      be the functional homologue of E.coli MutT in S.cerevisiae.

PMID- 15475387
TI  - Human MutL homolog (MLH1) function in DNA mismatch repair: a prospective screen
      for missense mutations in the ATPase domain.
AB  - Germline mutations in the DNA mismatch repair (MMR) genes MSH2 and MLH1 are
      responsible for the majority of hereditary non-polyposis colorectal cancer
      (HNPCC), an autosomal-dominant early-onset cancer syndrome. Genetic testing of
      both MSH2 and MLH1 from individuals suspected of HNPCC has revealed a
      considerable number of missense codons, which are difficult to classify as either
      pathogenic mutations or silent polymorphisms. To identify novel MLH1 missense
      codons that impair MMR activity, a prospective genetic screen in the yeast
      Saccharomyces cerevisiae was developed. The screen utilized hybrid human-yeast
      MLH1 genes that encode proteins having regions of the yeast ATPase domain
      replaced by homologous regions from the human protein. These hybrid MLH1 proteins
      are functional in MMR in vivo in yeast. Mutagenized MLH1 fragments of the human
      coding region were synthesized by error-prone PCR and cloned directly in yeast by
      in vivo gap repair. The resulting yeast colonies, which constitute a library of
      hybrid MLH1 gene variants, were initially screened by semi-quantitative in vivo
      MMR assays. The hybrid MLH1 genes were recovered from yeast clones that exhibited
      a MMR defect and sequenced to identify alterations in the mutagenized region.
      This investigation identified 117 missense codons that conferred a 2-fold or
      greater decreased efficiency of MMR in subsequent quantitative MMR assays.
      Notably, 10 of the identified missense codons were equivalent to codon changes
      previously observed in the human population and implicated in HNPCC. To
      investigate the effect of all possible codon alterations at single residues, a
      comprehensive mutational analysis of human MLH1 codons 43 (lysine-43) and 44
      (serine-44) was performed. Several amino acid replacements at each residue were
      silent, but the majority of substitutions at lysine-43 (14/19) and serine-44
      (18/19) reduced the efficiency of MMR. The assembled data identifies amino acid
      substitutions that disrupt MLH1 structure and/or function, and should assist the
      interpretation of MLH1 genetic tests.

PMID- 15475389
TI  - A dynamic, web-accessible resource to process raw microarray scan data into
      consolidated gene expression values: importance of replication.
AB  - We propose a freely accessible web-based pipeline, which processes raw microarray
      scan data to obtain experimentally consolidated gene expression values. The tool
      MADSCAN, which stands for MicroArray Data Suites of Computed ANalysis, makes a
      practical choice among the numerous methods available for filtering, normalizing
      and scaling of raw microarray expression data in a dynamic and automatic way.
      Different statistical methods have been adapted to extract reliable information
      from replicate gene spots as well as from replicate microarrays for each
      biological situation under study. A carefully constructed experimental design
      thus allows to detect outlying expression values and to identify statistically
      significant expression values, together with a list of quality controls with
      proposed threshold values. The integrated processing procedure described here,
      based on multiple measurements per gene, is decisive for reliably monitoring
      subtle gene expression changes typical for most biological events.

PMID- 15475391
TI  - A comprehensive and validated molecular taxonomy of beaked whales, family
      Ziphiidae.
AB  - DNA sequences from orthologous loci can provide universal characters for
      taxonomic identification. Molecular taxonomy is of particular value for groups in
      which distinctive morphological features are difficult to observe or compare. To
      assist in species identification for the little known family Ziphiidae (beaked
      whales), we compiled a reference database of mitochondrial DNA (mtDNA) control
      region (437 bp) and cytochrome b (384 bp) sequences for all 21 described species
      in this group. This mtDNA database is complemented by a nuclear database of actin
      intron sequences (925 bp) for 17 of the 21 species. All reference sequences were
      derived from specimens validated by diagnostic skeletal material or other
      documentation, and included four holotypes. Phylogenetic analyses of mtDNA
      sequences confirmed the genetic distinctiveness of all beaked whale species
      currently recognized. Both mitochondrial loci were well suited for species
      identification, with reference sequences for all known ziphiids forming robust
      species-specific clades in phylogenetic reconstructions. The majority of species
      were also distinguished by nuclear alleles. Phylogenetic comparison of sequence
      data from "test" specimens to these reference databases resulted in three major
      taxonomic discoveries involving animals previously misclassified from morphology.
      Based on our experience with this family and the order Cetacea as a whole, we
      suggest that a molecular taxonomy should consider the following components:
      comprehensiveness, validation, locus sensitivity, genetic distinctiveness and
      exclusivity, concordance, and universal accessibility and curation.

PMID- 15475390
TI  - Intramolecular quadruplex conformation of human telomeric DNA assessed with 125I
      radioprobing.
AB  - A repeated non-coding DNA sequence d(TTAGGG)n is present in the telomeric ends of
      all human chromosomes. These repeats can adopt multiple inter and intramolecular
      non-B-DNA conformations that may play an important role in biological processes.
      Two intramolecular structures of the telomeric oligonucleotide dAGGG(TTAGGG)3,
      antiparallel and parallel, have been solved by NMR and X-ray crystallography. In
      both structures, the telomeric sequence adopts an intramolecular quadruplex
      structure that is stabilized by G-4 quartets, but the ways in which the sequence
      folds into the quadruplex are different. The folds of the human telomeric DNA
      were described as an anti-parallel basket-type and a parallel propeller-type. We
      applied 125I-radioprobing to determine the conformation of the telomeric
      quadruplex in solution, in the presence of either Na+ or K+ ions. The probability
      of DNA breaks caused by decay of 125I is inversely related to the distance
      between the radionuclide and the sugar unit of the DNA backbone; hence, the
      conformation of the DNA backbone can be deduced from the distribution of breaks.
      The probability of breaks measured in the presence of Na+ and K+ were compared
      with the distances in basket-type and propeller-type quadruplexes obtained from
      the NMR and crystal structures. Our radioprobing data demonstrate that the
      antiparallel conformation was present in solution in the presence of both K+ and
      Na+. The preferable conformation in the Na+-containing solution was the basket
      type antiparallel quadruplex whereas the presence of K+ favored the chair-type
      antiparallel quadruplex. Thus, we believe that the two antiparallel and the
      parallel conformations may coexist in solution, and that their relative
      proportion is determined by the type and concentration of ions.

PMID- 15475392
TI  - Genetic evidence for hybridization of pallid and shovelnose sturgeon.
AB  - To determine the genetic origin of individual sturgeon that are morphologically
      intermediate to pallid (Scaphirhynchus albus) and shovelnose (Scaphirhynchus
      platorhynchus) sturgeon, we combined previously published mitochondrial DNA
      (mtDNA) and microsatellite data with additional microsatellite data. Two
      sympatric populations of pallid and shovelnose sturgeon from the upper Missouri
      River and a sympatric population containing pallid, shovelnose, and putative
      pallid-shovelnose hybrids from the Atchafalaya River were analyzed using an index
      of hybridization and a principle components analysis of individual relatedness
      scores. The addition of new microsatellite data improved our ability to
      genetically differentiate individual pallid and shovelnose sturgeon collected in
      both areas. Our methods distinguished morphologically intermediate Atchafalaya
      River sturgeon, which appear to be genetically intermediate between pallid and
      shovelnose sturgeon. The results support a hybrid origin for morphologically
      intermediate individuals, although it is unclear whether they are all first
      generation hybrids or if some are the result of subsequent backcrossing with the
      more common shovelnose sturgeon.

PMID- 15475393
TI  - Pleiotropy, epistasis and new QTL: the genetic architecture of honey bee foraging
      behavior.
AB  - The regulation of division of labor in social insects, particularly in the honey
      bee (Apis mellifera L.), has received considerable attention from a number of
      biological subdisciplines, including quantitative and behavioral genetics,
      because of the high complexity of the behavioral traits involved. The foraging
      choices of honey bee workers can be accurately quantified, and previous studies
      have made the foraging behavior of honey bees one of the best studied naturally
      occurring behavioral phenotypes. Three quantitative trait loci (QTL) have been
      identified that influence a set of foraging variables, including the
      concentration of nectar collected and the amount of pollen and nectar brought
      back to the hive. This study extends previous genetic investigations and
      represents the most comprehensive investigation of the genetic architecture of
      these foraging variables. We examined the effects of markers for the three
      established QTL and for one further candidate gene (Amfor), in two reciprocal
      backcross populations. These populations were also used to carry out two new QTL
      mapping studies, with over 400 Amplified Fragment Length Polymorphism (AFLP)
      markers in each. We detected a variety of effects of the genetic markers for the
      established QTL and the candidate gene, which were mostly epistatic in nature. A
      few new QTL could be detected with a variety of mapping techniques. Our results
      add complexity to the genetic architecture of the foraging behavior of the honey
      bee. Specifically, we support the hypotheses that pln1, pln2, pln3, and Amfor are
      involved in the regulation of foraging behavior in the honey bee and add some new
      factors that deserve further study in the future.

PMID- 15475394
TI  - The Psm locus controls paternal sorting of the cucumber mitochondrial genome.
AB  - The mitochondrial genome of cucumber shows paternal transmission and there are no
      reports of variation for mitochondrial transmission in cucumber. We used a
      mitochondrially encoded mosaic (MSC) phenotype to reveal phenotypic variation for
      mitochondrial-genome transmission in cucumber. At least 10 random plants from
      each of 71 cucumber plant introductions (PIs) were crossed as the female with an
      inbred line (MSC16) possessing the MSC phenotype. Nonmosaic F1 progenies were
      observed at high frequencies (greater than 50%) in F1 families from 10 PIs, with
      the greatest proportions being from PI 401734. Polymorphisms near the
      mitochondrial cox1 gene and JLV5 region revealed that nonmosaic hybrid progenies
      from crosses of PI 401734 with MSC16 as the male possessed the nonmosaic-inducing
      mitochondrial DNA (mtDNA) from the paternal parent. F2) F3, and backcross
      progenies from nonmosaic F1 plants from PI 401734 x MSC16 were testcrossed with
      MSC16 as the male parent to reveal segregation of a nuclear locus (Psm for
      Paternal sorting of mitochondria) controlling sorting of mtDNA from the paternal
      parent. Psm is a unique locus at which the maternal genotype affects sorting of
      paternally transmitted mtDNA.

PMID- 15475395
TI  - Inheritance of resistance to zucchini yellow mosaic virus and watermelon mosaic
      virus in watermelon.
AB  - High resistance to zucchini yellow mosaic virus-China strain (ZYMV-CH) and
      moderate resistance to watermelon mosaic virus (WMV) were found in a selection of
      PI 595203 (Citrullus lanatus var. lanatus), an Egusi type originally collected in
      Nigeria. Mixed inoculations showed primarily that these two viruses have no cross
      protection. This fact may explain the high frequency of mixed infection often
      observed in commercial fields. When plants were inoculated with a mixture of the
      two viruses, the frequency of plants resistant to ZYMV was lower than expected,
      indicating that WMV infection may reduce the ability of a plant to resist ZYMV.
      We studied inheritance of resistance to ZYMV-CH and WMV, using crosses between a
      single-plant selection of PI 595203 and the ZYMV-susceptible watermelon inbreds
      9811 and 98R. According to virus ratings of the susceptible parents, the
      resistant parent, and the F1, F2, and BC1 generations, resistance to ZYMV-CH was
      conferred by a single recessive gene, for which the symbol zym-CH is suggested.
      The high tolerance to WMV was controlled by at least two recessive genes.

PMID- 15475396
TI  - Experiments in DNA extraction and PCR amplification from bighorn sheep feces: the
      importance of DNA extraction method.
AB  - Reliability of genotyping is an issue for studies using non-invasive sources of
      DNA. We emphasize the importance of refining DNA extraction methods to maximize
      reliability and efficiency of genotyping for such DNA sources. We present a
      simple and general method to quantitatively compare genotyping reliability of
      various DNA extraction techniques and sample materials used. For bighorn sheep
      (Ovis canadensis) fecal samples we compare different fecal pellet materials,
      different amounts of fecal pellet material, and the effects of eliminating two
      DNA extraction steps for four microsatellite loci and four samples heterozygous
      at each locus. We evaluated 192 PCR outcomes for each treatment using indices of
      PCR success and peak height (signal strength) developed from analysis output of
      sequencer chromatograms. Outermost pellet material produced PCR results almost
      equivalent to DNA extracted from blood. Where any inner pellet material was used
      for DNA extraction, PCR results were poorer and inconsistent among samples. PCR
      success was not sensitive to amount of pellet material used until it was
      decreased to 15 mg from 60 mg. Our PCR index provides considerably more
      information relative to potential genotyping errors than simply comparing
      genotypes derived from paired fecal and blood or tissue samples. Our DNA
      extraction method probably has wide applicability to herbivores that produce
      pelleted feces where samples dry rapidly after deposition.

PMID- 15475397
TI  - Reduced female gene flow in the European flat oyster Ostrea edulis.
AB  - The geographical structure of 15 natural populations of the flat oyster (Ostrea
      edulis L.) was assessed by single-strand conformation polymorphism (SSCP) of a
      313-base-pair (bp) fragment of the mitochondrial 12S-rRNA gene. Fourteen
      haplotypes were observed, with one being dominant in the Mediterranean samples
      and another one in the Atlantic populations. The geographically extreme
      populations sampled in Norway and the Black Sea appeared differentiated by
      exhibiting the dominance of a third group of haplotypes. The results were
      compared to available microsatellite data at five loci. The
      Atlantic/Mediterranean differentiation pattern was qualitatively the same with
      both types of markers, confirming an isolation-by-distance pattern. The average
      mitochondrial haplotypic diversity displayed a high among populations variance,
      reflecting small effective population size in some locations. Additionally, a 10
      fold quantitative difference was observed in Fst between the mitochondrial and
      the nuclear genomes, which could be due to an unbalanced sex ratio or sex-biased
      differential reproductive success between males and females (or both).

PMID- 15475398
TI  - Cytogenetic studies in three Pimelodella meeki populations (Pisces, Pimelodidae)
      from Tibagi River basin (Brazil).
AB  - We analyzed cytogenetically specimens of Pimelodella meeki from Tibagi River at
      Limoeiro (LM) and from two tributaries, Couro do Boi (CB) and Gabriel da Cunha
      (GC) Rivers. All specimens presented 2n=46 chromosomes, which were the karyotypes
      composed by 15 pairs metacentric (M) + 6 pairs submetacentric (SM) + 2 pairs
      subtelocentric (ST). In specimens of GC, CB, and LM, the results of analyses of
      the nucleolus organizer regions (NORs), done by means of AgNO3 and CMA3 staining,
      showed that they are identical, located in terminal position on the short arm of
      a SM chromosome pair, and they were observed to be a size heteromorphism in some
      metaphase plates. FISH with 18S rDNA probe yielded evidence for these regions but
      not for the size variation, indicating that they are not due to a greater number
      of NOR cistrons in one of the homologue chromosomes. An interesting
      characteristic of these regions is that they could appear divided in blocks, as
      evidenced by all the techniques. This work makes clear the necessity for more
      deeply systematic studies, because of the confused taxonomic situation of the
      genus Pimelodella.

PMID- 15475399
TI  - Cross-species amplification of Bovidae microsatellites and low diversity of the
      endangered Korean goral.
AB  - The Korean goral (Nemorhaedus caudatus) is an endangered species of wild goat.
      The conservation and management of this species could benefit from a better
      understanding of its genetic diversity and structure. Cross-species amplification
      of 34 Bovidae microsatellite loci was tested on a panel of 6 Korean gorals and 10
      domestic goats. After polymerase chain reaction (PCR) optimization, 29 (85.3%)
      microsatellite loci amplified successfully for the Korean gorals and 27 (79.4%)
      for the domestic goats. Of the amplified products, 16 (55.2%) were polymorphic in
      the Korean goral and 22 (81.5%) in domestic goats. Nei's unbiased mean
      heterozygosity and mean allele number per locus were, respectively, 0.356 and 2.6
      in the Korean goral and 0.636 and 4.8 in domestic goats. Low genetic diversity in
      the Korean gorals observed in this preliminary microsatellite survey suggests an
      urgent need for further detailed study of genetic diversity in Korean goral
      populations and a population management strategy based on these studies. Current
      results of cross-species amplification of domestic Bovidae microsatellites could
      be employed for the necessary population genetic studies on the Korean goral and
      other endangered Caprinae species.

PMID- 15475400
TI  - Analysis of the inheritance of white spotting and the evaluation of KIT and EDNRB
      as spotting loci in Dutch boxer dogs.
AB  - The genetic basis of the white spotting pattern in Dutch boxer dogs is not known.
      We studied whether the segregation of white spotting in boxers follows a
      Mendelian inheritance pattern. Blood samples were collected, along with digital
      photographs in standard directions of (grand)parents (n=16) and offspring (n=52)
      from eight litters of Dutch boxers. In order to select heterozygous parents, we
      selected nonuniform litters, in which at least one puppy was extreme white. On
      the basis of criteria for the location, the extent of white spotting, and the
      mean percentage of pigmented area of the foot soles, we classified 10 dogs as
      solid colored, 27 as flashy, and 15 as extreme white. This was not a significant
      deviation from the expected 1:2:1 ratio. Because the flashy phenotype seems to be
      an intermediate between the two homozygotes, white spotting in the Dutch boxer
      can be considered to be due to a single gene effect, with incomplete dominance.
      We have evaluated candidate genes c-KIT (KIT) and EDNRB for segregation with
      white spotting phenotype in these litters. Using polymorphic markers, very near
      the KIT and EDNRB genes, we found that segregation of the white spotting pattern
      did not coincide with segregation of these polymorphic markers. Thus neither KIT
      nor EDNRB are likely to be responsible for white spotting in the Dutch population
      of boxers.

PMID- 15475401
TI  - Segregation distortion for seed testa color in Mungbean (Vigna radiata L.
      Wilcek).
AB  - Genetic segregation experiments with plant species are commonly used for
      understanding the inheritance of traits. A basic assumption in these experiments
      is that each gamete developed from megasporogenesis has an equal chance of fusing
      with a gamete developed from microsporogenesis, and every zygote formed has an
      equal chance of survival. If gametic and/or zygotic selection occurs whereby
      certain gametes or zygotic combinations have a reduced chance of survival,
      progeny distributions are skewed and are said to exhibit segregation distortion.
      In this study, inheritance data are presented for the trait seed testa color
      segregating in large populations (more than 200 individuals) derived from closely
      related mungbean (Vigna radiata L. Wilcek) taxa. Segregation ratios suggested
      complex inheritance, including dominant and recessive epistasis. However, this
      genetic model was rejected in favor of a single-gene model based on evidence of
      segregation distortion provided by molecular marker data. The segregation
      distortion occurred after each generation of self-pollination from F1 thru F7
      resulting in F7 phenotypic frequencies of 151:56 instead of the expected
      103.5:103.5. This study highlights the value of molecular markers for
      understanding the inheritance of a simply inherited trait influenced by
      segregation distortion.

PMID- 15475402
TI  - GENECLASS2: a software for genetic assignment and first-generation migrant
      detection.
AB  - GENECLASS2 is a software that computes various genetic assignment criteria to
      assign or exclude reference populations as the origin of diploid or haploid
      individuals, as well as of groups of individuals, on the basis of multilocus
      genotype data. In addition to traditional assignment aims, the program allows the
      specific task of first-generation migrant detection. It includes several Monte
      Carlo resampling algorithms that compute for each individual its probability of
      belonging to each reference population or to be a resident (i.e., not a first
      generation migrant) in the population where it was sampled. A user-friendly
      interface facilitates the treatment of large datasets.

PMID- 15475403
TI  - Fishing in the bloodstream: insights into the mechanisms of pulmonary
      hypertension?

PMID- 15475404
TI  - Histopathologic diagnosis in diffuse lung disease: an ailing gold standard.

PMID- 15475405
TI  - Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma
      Control study.

PMID- 15475406
TI  - Fluoroquinolones in multidrug-resistant tuberculosis.

PMID- 15475407
TI  - Exacerbations of chronic obstructive pulmonary disease: should self-management be
      used?

PMID- 15475410
TI  - Arabidopsis HMA2, a divalent heavy metal-transporting P(IB)-type ATPase, is
      involved in cytoplasmic Zn2+ homeostasis.
AB  - PIB-type ATPases transport heavy metal ions (Cu+, Cu2+, Zn2+, Cd2+, Co2+, etc.)
      across biological membranes. Several members of this subfamily are present in
      plants. Higher plants are the only eukaryotes where putative Zn(2+)-ATPases have
      been identified. We have cloned HMA2, a PIB-ATPase present in Arabidopsis
      (Arabidopsis thaliana), and functionally characterized this enzyme after
      heterologous expression in yeast (Saccharomyces cerevisiae). HMA2 is a Zn(2+)
      dependent ATPase that is also activated by Cd2+ and, to a lesser extent, by other
      divalent heavy metals (Pb2+, Ni2+, Cu2+, and Co2+). The enzyme forms an acid
      stable phosphorylated intermediate and is inhibited by vanadate. HMA2 interacts
      with Zn2+ and Cd2+ with high affinity (Zn2+ K(1/2) = 0.11 +/- 0.03 microm and
      Cd2+ K(1/2) = 0.031 +/- 0.007 microm). However, its activity is dependent on
      millimolar concentrations of Cys in the assay media. Zn2+ transport
      determinations indicate that the enzyme drives the outward transport of metals
      from the cell cytoplasm. Analysis of HMA2 mRNA suggests that the enzyme is
      present in all plant organs and transcript levels do not change in plants exposed
      to various metals. Removal of HMA2 full-length transcript results in Zn2+
      accumulation in plant tissues. hma2 mutant plants also accumulate Cd2+ when
      exposed to this metal. These results suggest that HMA2 is responsible for Zn2+
      efflux from the cells and therefore is required for maintaining low cytoplasmic
      Zn2+ levels and normal Zn2+ homeostasis.

PMID- 15475411
TI  - Structural and functional diversity in heme monooxygenases.
AB  - Recent advances in understanding structure-function relationships in cytochrome
      P450 (P450), nitric-oxide synthase (NOS), and heme oxygenase are summarized. Of
      particular importance is the role that dynamics plays in P450 function, where the
      active site undergoes large open/close motions to enable substrates to bind and
      products to leave. In sharp contrast, the heme-containing active site of NOS is
      rigid and remains relatively exposed compared with P450s. This difference in
      dynamics and active site exposure requires that the O(2) activation machinery
      operate somewhat differently in P450 and NOS. Owing to the open NOS active site,
      the NOS-oxy complex could be subject to nonspecific protonation that short
      circuits the normal reaction path. One working hypothesis holds that NOS
      recruited the cofactor, tetrahydrobiopterin, to bind near the heme for very rapid
      coupled electron/proton transfer to the oxy complex, which avoids indiscriminate
      reaction with bulk solvent. Despite these differences, P450, NOS, and also heme
      oxygenase use a very similar network of H-bonded water molecules in the active
      site that are required for oxygen activation. Both P450 and NOS are important
      drug targets. With NOS, the structural basis for isoform-selective inhibition by
      a class of dipeptide inhibitors has been worked out, thus providing the basis for
      structure-based drug design.

PMID- 15475412
TI  - Characterization of afloqualone N-glucuronidation: species differences and
      identification of human UDP-glucuronosyltransferase isoform(s).
AB  - Afloqualone (AFQ) is one of the centrally acting muscle relaxants. AFQ N
      glucuronide is the most abundant metabolite in human urine when administered
      orally, whereas it was not detected in the urine when administered to rats, dogs,
      and monkeys. Species differences in AFQ N-glucuronidation were investigated with
      liver microsomes obtained from humans and experimental animals. The kinetics of
      AFQ N-glucuronidation in human liver microsomes showed a typical Michaelis-Menten
      plot. The K(m) and V(max) values accounted for 2019 +/- 85.9 muM and 871.2 +/-
      17.9 pmol/min/mg protein, respectively. The V(max) and intrinsic clearance
      (CL(int)) values of AFQ N-glucuronidation in human liver were approximately 4- to
      10-fold and 2- to 4-fold higher than those in rat, dog, and monkey, respectively.
      Among 12 recombinant human UDP-glucuronosyltransferase (UGT) isoforms, both
      UGT1A4 and UGT1A3 exhibited high AFQ N-glucuronosyltransferase activities. The
      K(m) value of AFQ N-glucuronidation in recombinant UGT1A4 microsomes was very
      close to that in human liver microsomes. The formation of AFQ N-glucuronidation
      by human liver, jejunum, and recombinant UGT1A4 microsomes was effectively
      inhibited by trifluoperazine, a known specific substrate for UGT1A4. The AFQ N
      glucuronidation activities in seven human liver microsomes were significantly
      correlated with trifluoperazine N-glucuronidation activities (r(2) = 0.798, p <
      0.01). In contrast, the K(m) value of AFQ N-glucuronidation in recombinant UGT1A3
      microsomes was relatively close to that in human jejunum microsomes. These
      results demonstrate that AFQ N-glucuronidation in human is mainly catalyzed by
      UGT1A4 in the liver and by UGT1A3, as well as UGT1A4 in the intestine.

PMID- 15475415
TI  - Nonparametric estimation of the effects of quantitative trait loci.
AB  - Interval mapping of quantitative trait loci from breeding experiments plays an
      important role in understanding the mechanisms of disease, both in humans and
      other organisms. Standard approaches to estimation involve parametric assumptions
      for the component distributions and may be sensitive to model misspecification.
      Some nonparametric tests have been studied. However, nonparametric estimation of
      the phenotypic distributions has not been considered in the genetics literature,
      even though such methods might provide essential nonparametric summaries for
      comparing different loci. We develop a sufficient condition for identifiability
      of the phenotypic distributions. Simple nonparametric estimators for the
      distributions are proposed for uncensored and right censored data. They have a
      closed form and their small and large sample properties are readily established.
      Their practical utility as numerical summaries which complement nonparametric
      tests is demonstrated on two recent genetics examples.

PMID- 15475413
TI  - Functional assessment of ABCG2 (BCRP) gene polymorphisms to protein expression in
      human placenta.
AB  - The aim of the present study was to assess the contribution of polymorphisms in
      the breast cancer resistance protein/ATP-binding cassette transporter G2
      (BCRP/ABCG2) gene to the placental expression from a new perspective, allelic
      imbalance. Polymorphisms were screened by polymerase chain reaction (PCR)-single
      strand conformation polymorphism analysis followed by sequencing with DNA
      extracted from 100 placentas. To examine whether polymorphisms of the BCRP gene
      correlate with the placental BCRP expression, we determined mRNA and protein
      levels by quantitative real-time PCR and Western blotting, respectively. In
      placentas, G34A (Val(12)Met) and C421A (Gln(141)Lys) were frequently observed (18
      36%), but C376T, which creates a stop codon (Gln(126) stop codon), was found with
      an allelic frequency of 1%. The mean of the BCRP protein level was significantly
      lower (p < 0.05) in homozygotes for the A421 allele than in those for the C421
      allele, and heterozygotes had an intermediate value. To evaluate whether the
      C421A polymorphism acts as a cis-element in BCRP transcription, allelic imbalance
      was determined using informative lymphoblasts and 56 samples of placental cDNA.
      In most of the placental samples we tested, the difference in expression levels
      between the two alleles was small, and only two samples indicated a monoallelic
      expression (i.e., preferential expression of one allele). These results suggest
      that 1) the predominant allelic expression pattern of BCRP in placental samples
      is biallelic, and 2) the mutation C421A is not a genetic variant acting in cis,
      but is considered to influence the translation efficiency.

PMID- 15475416
TI  - Identifying multiple changepoints in heterogeneous binary data with an
      application to molecular genetics.
AB  - Identifying changepoints is an important problem in molecular genetics. Our
      motivating example is from cancer genetics where interest focuses on identifying
      areas of a chromosome with an increased likelihood of a tumor suppressor gene.
      Loss of heterozygosity (LOH) is a binary measure of allelic loss in which abrupt
      changes in LOH frequency along the chromosome may identify boundaries indicative
      of a region containing a tumor suppressor gene. Our interest was on testing for
      the presence of multiple changepoints in order to identify regions of increased
      LOH frequency. A complicating factor is the substantial heterogeneity in LOH
      frequency across patients, where some patients have a very high LOH frequency
      while others have a low frequency. We develop a procedure for identifying
      multiple changepoints in heterogeneous binary data. We propose both approximate
      and full maximum-likelihood approaches and compare these two approaches with a
      naive approach in which we ignore the heterogeneity in the binary data. The
      methodology is used to estimate the pattern in LOH frequency on chromosome 13 in
      esophageal cancer patients and to isolate an area of inflated LOH frequency on
      chromosome 13 which may contain a tumor suppressor gene. Using simulations, we
      show that our approach works well and that it is robust to departures from some
      key modeling assumptions.

PMID- 15475417
TI  - Sensitivity analysis of longitudinal binary data with non-monotone missing
      values.
AB  - This paper highlights the consequences of incomplete observations in the analysis
      of longitudinal binary data, in particular non-monotone missing data patterns.
      Sensitivity analysis is advocated and a method is proposed based on a log-linear
      model. A sensitivity parameter that represents the relationship between the
      response mechanism and the missing data mechanism is introduced. It is shown that
      although this parameter is identifiable, its estimation is highly questionable. A
      far better approach is to consider a range of plausible values and to estimate
      the parameters of interest conditionally upon each value of the sensitivity
      parameter. This allows us to assess the sensitivity of study's conclusion to
      assumptions regarding the missing data mechanism. The method is applied to a
      randomized clinical trial comparing the efficacy of two treatment regimens in
      patients with persistent asthma.

PMID- 15475418
TI  - Maximum likelihood estimation of oncogenetic tree models.
AB  - We present a new approach for modelling the dependences between genetic changes
      in human tumours. In solid tumours, data on genetic alterations are usually only
      available at a single point in time, allowing no direct insight into the
      sequential order of genetic events. In our approach, genetic tumour development
      and progression is assumed to follow a probabilistic tree model. We show how
      maximum likelihood estimation can be used to reconstruct a tree model for the
      dependences between genetic alterations in a given tumour type. We illustrate the
      use of the proposed method by applying it to cytogenetic data from 173 cases of
      clear cell renal cell carcinoma, arriving at a model for the karyotypic evolution
      of this tumour.

PMID- 15475419
TI  - Circular binary segmentation for the analysis of array-based DNA copy number
      data.
AB  - DNA sequence copy number is the number of copies of DNA at a region of a genome.
      Cancer progression often involves alterations in DNA copy number. Newly developed
      microarray technologies enable simultaneous measurement of copy number at
      thousands of sites in a genome. We have developed a modification of binary
      segmentation, which we call circular binary segmentation, to translate noisy
      intensity measurements into regions of equal copy number. The method is evaluated
      by simulation and is demonstrated on cell line data with known copy number
      alterations and on a breast cancer cell line data set.

PMID- 15475420
TI  - Semi-parametric estimation of the binormal ROC curve for a continuous diagnostic
      test.
AB  - Not until recently has much attention been given to deriving maximum likelihood
      methods for estimating the intercept and slope parameters from a binormal ROC
      curve that assesses the accuracy of a continuous diagnostic test. We propose two
      new methods for estimating these parameters. The first method uses the profile
      likelihood and a simple algorithm to produce fully efficient estimates. The
      second method is based on a pseudo-maximum likelihood that can easily accommodate
      adjusting for covariates that could affect the accuracy of the continuous test.

PMID- 15475421
TI  - Bayesian analysis of binary prediction tree models for retrospectively sampled
      outcomes.
AB  - Classification tree models are flexible analysis tools which have the ability to
      evaluate interactions among predictors as well as generate predictions for
      responses of interest. We describe Bayesian analysis of a specific class of tree
      models in which binary response data arise from a retrospective case-control
      design. We are also particularly interested in problems with potentially very
      many candidate predictors. This scenario is common in studies concerning gene
      expression data, which is a key motivating example context. Innovations here
      include the introduction of tree models that explicitly address and incorporate
      the retrospective design, and the use of nonparametric Bayesian models involving
      Dirichlet process priors on the distributions of predictor variables. The model
      specification influences the generation of trees through Bayes' factor based
      tests of association that determine significant binary partitions of nodes during
      a process of forward generation of trees. We describe this constructive process
      and discuss questions of generating and combining multiple trees via Bayesian
      model averaging for prediction. Additional discussion of parameter selection and
      sensitivity is given in the context of an example which concerns prediction of
      breast tumour status utilizing high-dimensional gene expression data; the example
      demonstrates the exploratory/explanatory uses of such models as well as their
      primary utility in prediction. Shortcomings of the approach and comparison with
      alternative tree modelling algorithms are also discussed, as are issues of
      modelling and computational extensions.

PMID- 15475422
TI  - Overdiagnosis in early detection programs.
AB  - Overdiagnosis refers to the situation where a screening exam detects a disease
      that would have otherwise been undetected in a person's lifetime. The disease
      would have not have been diagnosed because the individual would have died of
      other causes prior to its clinical onset. Although the probability of
      overdiagnosis is an important quantity for understanding early detection programs
      it has not been rigorously studied. We analyze an idealized early detection
      program and derive the mathematical expression for the probability of
      overdiagnosis. The results are studied numerically for prostate cancer and
      applied to a variety of screening schedules. Our investigation indicates that the
      probability of overdiagnosis is remarkably high.

PMID- 15475424
TI  - Mixed models for the analysis of replicated spatial point patterns.
AB  - The statistical methodology for the analysis of replicated spatial point patterns
      in complex designs such as those including replications is fairly undeveloped. A
      mixed model is developed in conjunction with maximum pseudolikelihood and
      generalized linear mixed modeling by extending Baddeley and Turner's (2000,
      Australian and New Zealand Journal of Statistics 42, 283-322) work on
      pseudolikelihood for single patterns. A simulation experiment is performed on
      parameter estimation. Fixed- and mixed-effect models are compared, and in some
      respects the mixed model is found to be superior. An example using the Strauss
      process for modeling neuron locations in post-mortem brain slices is shown.

PMID- 15475423
TI  - Semiparametric estimation of time-dependent ROC curves for longitudinal marker
      data.
AB  - One approach to evaluating the strength of association between a longitudinal
      marker process and a key clinical event time is through predictive regression
      methods such as a time-dependent covariate hazard model. For example, a Cox model
      with time-varying covariates specifies the instantaneous risk of the event as a
      function of the time-varying marker and additional covariates. In this manuscript
      we explore a second complementary approach which characterizes the distribution
      of the marker as a function of both the measurement time and the ultimate event
      time. Our goal is to extend the standard diagnostic accuracy concepts of
      sensitivity and specificity so as to recognize explicitly both the timing of the
      marker measurement and the timing of disease. The accuracy of a longitudinal
      marker can be fully characterized using time-dependent receiver operating
      characteristic (ROC) curves. We detail a semiparametric estimation method for
      time-dependent ROC curves that adopts a regression quantile approach for
      longitudinal data introduced by Heagerty and Pepe (1999, Applied Statistics, 48,
      533-551). We extend the work of Heagerty and Pepe (1999, Applied Statistics, 48,
      533-551) by developing asymptotic distribution theory for the ROC estimators
      where the distributional shape for the marker is allowed to depend on covariates.
      To illustrate our method, we analyze pulmonary function measurements among cystic
      fibrosis subjects and estimate ROC curves that assess how well the pulmonary
      function measurement can distinguish subjects that progress to death from
      subjects that remain alive. Comparing the results from our semiparametric
      analysis to a fully parametric method discussed by Etzioni et al. (1999, Medical
      Decision Making, 19, 242-251) suggests that the ability to relax distributional
      assumptions may be important in practice.

PMID- 15475425
TI  - Gel-based proteomics: what does MCP expect?

PMID- 15475426
TI  - More than a marker... Phosphorylated Akt in prostate carcinoma.

PMID- 15475427
TI  - A phase I study of topical Tempol for the prevention of alopecia induced by whole
      brain radiotherapy.
AB  - PURPOSE: Complete alopecia is a universal complication of whole brain radiation
      therapy which contributes to patient anxiety over treatment. Tempol, a nitroxide
      radioprotector, has been shown to protect against radiation-induced alopecia in
      an animal model. This phase Ib study was designed to evaluate the safety and side
      effect profile of topical Tempol in patients with brain metastases being treated
      with whole brain radiotherapy. EXPERIMENTAL DESIGN: Twelve patients with
      metastatic cancer to the brain were enrolled in the study between October 2000
      and February 2003. Tempol (70 mg/ml concentration solution) was applied topically
      to the scalp 15 minutes before and washed off immediately after the completion of
      each of 10 fractions of whole brain radiation. Pharmacokinetic studies to
      evaluate the systemic absorption of Tempol were performed. Patients were assessed
      for toxicity before, during, and after Tempol administration. A secondary end
      point of the study, hair retention, was also scored. RESULTS: Eleven patients
      were treated with topical Tempol. Adverse events that were considered possibly,
      probably, or definitely related to Tempol, included asymptomatic grade 2 (two
      patients) and grade 1 (one patient) hypoglycemia, grade 1 forehead skin redness
      (one patient), grade 1 dry scalp (one patient), and grade 1 tingling sensation on
      the scalp (one patient). Tempol was not detected in blood samples from more than
      50% of the patients. Mean maximum Tempol levels for individual patients at any
      time point varied from 0.4 to 3.1 micromol/L. Hair retention was localized to the
      base of the scalp where the Tempol solution pooled after application in the first
      four patients on the study. Subsequently, full scalp hair retention was seen in
      three of final five evaluable patients after gauze had been wrapped around the
      head to hold the solution against the scalp. CONCLUSIONS: This study demonstrates
      that topical application of Tempol to the scalp before whole brain radiation is
      safe and well tolerated. Evidence of protection against radiation-induced
      alopecia was observed. A phase II study that uses a gel formulation to increase
      the exposure of scalp to Tempol has been initiated.

PMID- 15475428
TI  - Immediate gene expression changes after the first course of neoadjuvant
      chemotherapy in patients with primary breast cancer disease.
AB  - PURPOSE: Our goal was to identify genes undergoing expressional changes shortly
      after the beginning of neoadjuvant chemotherapy for primary breast cancer.
      EXPERIMENTAL DESIGN: The biopsies were taken from patients with primary breast
      cancer prior to any treatment and 24 hours after the beginning of the neoadjuvant
      chemotherapy. Expression analyses from matched pair samples representing 25
      patients were carried out with Clontech filter arrays. A subcohort of those 25
      paired samples were additionally analyzed with the Affymetrix GeneChip platform.
      All of the transcripts from both platforms were queried for expressional changes.
      RESULTS: Performing hierarchical cluster analysis, we clustered pre- and
      posttreatment samples from individual patients more closely to each other than
      the samples taken from different patients. This reflects the rather low number of
      transcripts responding directly to the drugs used. Although transcriptional drug
      response occurring during therapy differed between individual patients, two genes
      (p21(WAF1/CIP1) and MIC-1) were up-regulated in posttreatment samples. This could
      be validated by semiquantitative and real-time reverse transcription-PCR. Partial
      least- discriminant analysis based on approximately 25 genes independently
      identified by either Clontech or Affymetrix platforms could clearly discriminate
      pre- and posttreatment samples. However, correlation of certain gene expression
      levels as well as of differential patterns and clusters as determined by a
      different platform was not always satisfying. CONCLUSIONS: This study has
      demonstrated the potential of monitoring posttreatment changes in gene expression
      as a measure of the pharmacodynamics of drugs. As a clinical laboratory model, it
      can be useful to identify patients with sensitive and reactive tumors and to help
      for optimized choice for sequential therapy and obviously improve relapse- free
      and overall survival.

PMID- 15475429
TI  - Characterization of active mitogen-activated protein kinase in ovarian serous
      carcinomas.
AB  - PURPOSE: Mitogen-activated protein kinase (MAPK) plays a pivotal role in signal
      transduction. Activation of MAPK is regulated by upstream kinases including KRAS
      and BRAF, which are frequently mutated in low-grade ovarian serous carcinoma.
      This study evaluates the expression of active MAPK in ovarian serous carcinomas,
      with response to treatment and survival. EXPERIMENTAL DESIGN: Expression of
      active MAPK was assessed by immunohistochemistry in 207 cases of ovarian serous
      tumors. Immunoreactivity was correlated with tumor grade, mutational status of
      KRAS and BRAF, in vitro drug resistance, and clinical outcome. RESULT: There was
      a lower frequency of expression of active MAPK in high-grade ovarian serous
      carcinomas as compared with low-grade serous tumors, including borderline tumors
      and low-grade serous carcinoma (P < 0.001). Active MAPK was present in all of the
      19 low-grade tumors with either KRAS or BRAF mutations as well as in 14 (41%) of
      34 tumors with wild-type KRAS and BRAF in both low- and high-grade carcinomas.
      Expression of active MAPK alone served as a good survival indicator in the 2-year
      follow-up (P = 0.037) but not in the 5-year follow-up (P = 0.145). However, a
      combination of expression of active MAPK and in vitro sensitivity of paclitaxel
      significantly correlated with a better prognosis in 5-year survival rate (P =
      0.048) in patients with advanced-stage high-grade serous carcinoma. CONCLUSIONS:
      Active MAPK is more frequently expressed in low-grade than in high-grade ovarian
      serous carcinoma. Active MAPK serves as a good prognostic marker in patients with
      high-grade serous carcinomas.

PMID- 15475430
TI  - Proliferation potential-related protein, an ideal esophageal cancer antigen for
      immunotherapy, identified using complementary DNA microarray analysis.
AB  - PURPOSE: To establish effective antitumor immunotherapy for esophageal cancer, we
      tried to identify an useful target antigen of esophageal cancer. EXPERIMENTAL
      DESIGN: We did cDNA microarray analysis to find a novel candidate antigen,
      proliferation potential-related protein (PP-RP). We examined cytotoxicity against
      tumor cells in vitro and in vivo of CTLs specific to PP-RP established from
      esophageal cancer patients. RESULTS: In 26 esophageal cancer tissues, an average
      of relative ratio of the expression of the PP-RP mRNA in cancer cells versus
      adjacent normal esophageal tissues was 396.2. Immunohistochemical analysis
      revealed that, in 20 of the 22 esophageal cancer tissues, PP-RP protein was
      strongly expressed only in the cancer cells and not so in normal esophageal
      epithelial cells. PP-RP protein contains 10 epitopes recognized by HLA-A24
      restricted CTLs. These CTLs, generated from HLA-A24-positive esophageal cancer
      patients, had cytotoxic activity against cancer cell lines positive for both PP
      RP and HLA-A24. Furthermore, adoptive transfer of the PP-RP-specific CTL line
      inhibited the growth of a human esophageal cancer cell line engrafted in nude
      mice. CONCLUSIONS: The expression of PP-RP in esophageal cancer cells was
      significantly higher than in normal cells, and the CTLs recognizing PP-RP killed
      tumor cells in vitro and also showed tumor rejection effects in a xenograft
      model. Therefore, PP-RP may prove to be an ideal tumor antigen useful for
      diagnosis and immunotherapy for patients with esophageal cancer. cDNA microarray
      analysis is a useful method to identify ideal tumor-associated antigens.

PMID- 15475432
TI  - [18F]Fluoro-2-deoxy-D-glucose positron emission tomography detects gastric
      carcinoma in an early stage in an asymptomatic E-cadherin mutation carrier.
AB  - PURPOSE: Autosomal dominant hereditary diffuse gastric cancer (HDGC) is caused by
      germ-line E-cadherin (CDH1) gene mutations. Early detection of cancer in carriers
      is difficult because HDGC escapes endoscopic detection. We hypothesized that the
      glucose metabolism is enhanced in HDGC and that this can be detected with
      [18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET).
      EXPERIMENTAL DESIGN AND RESULTS: An asymptomatic twenty-eight year-old female was
      seen at our outpatient clinic because of a request for screening on HDGC. Her
      father and younger sister died of diffuse gastric cancer, at the ages of 52 and
      27, respectively. Mutational analysis of the CDH1 gene in this patient
      demonstrated a novel heterozygous splice-site mutation in exon 8
      (1135delACGGTAATinsTTAGA). Upper gastrointestinal endoscopies revealed no
      macroscopic abnormalities, but one of the 40 random biopsy specimens showed well
      differentiated signet-cell carcinoma. A FDG-PET scan demonstrated two spots of
      FDG accumulation, one located in the proximal part of the stomach and the second
      in the region of the pylorus. A total gastrectomy was performed and microscopic
      examination showed focal localization of intramucosal adenocarcinoma of the
      signet-cell type in the cardiac and antrum area. Most notably, the localization
      of the FDG accumulation matched the localization of the carcinoma. CONCLUSIONS:
      We present an asymptomatic patient from a HDGC family carrying a novel CDH1
      mutation in whom FDG-PET scanning facilitated early detection of HDGC. This calls
      for further investigation of the role of FDG-PET scan as a screening modality in
      HDGC.

PMID- 15475431
TI  - Centrosome hyperamplification predicts progression and tumor recurrence in
      bladder cancer.
AB  - PURPOSE: Recent studies have reported that centrosome hyperamplification (CH) is
      closely related to chromosomal instability in bladder cancer. In this study, we
      investigated whether CH could be used as a prognostic biomarker for patients with
      bladder cancer. EXPERIMENTAL DESIGN: CH was evaluated by immunohistochemistry in
      50 bladder cancers (< or =pT1: 43; > or =pT2: 7). In addition, numerical
      aberrations of chromosomes 7, 9, and 17 and gain of 20q13, on which the Aurora-A
      gene is located, were evaluated by fluorescence in situ hybridization, and DNA
      ploidy was assessed. Preliminary experiments on eight bladder cancer cell lines
      found that six had over 5% of CH cells associated with a gain of 20q13 and
      overexpression of Aurora-A; therefore, CH-positive cases (CH+) were defined as
      those having over 5% of cells with > or =3 centrosomes per cell. RESULTS: CH+,
      20q13 gain, chromosomal instability, and DNA aneuploidy were detected in 30
      (60%), 18 (36%), 22 (44%), and 19 (38%) patients, respectively. There were
      significant differences in tumor number, grade, recurrence, and progression
      between the CH+ and CH- groups. The later had significantly higher recurrence
      free and progression-free survivals than the former (P = 0.0028 and P = 0.0070,
      respectively, log-rank test). Multivariate analysis revealed that CH+ was the
      strongest predictor for tumor recurrence in nonmuscle invasive (pTa and pT1)
      bladder cancer (hazard ratio, 1.882; 95% confidence interval, 1.161-3.325; P =
      0.0094). CONCLUSIONS: Detection of CH may provide crucial prognostic information
      about tumor recurrence in bladder cancer.

PMID- 15475433
TI  - Overexpression of matrix metalloproteinase-1 and -9 mRNA is associated with
      progression of oral dysplasia to cancer.
AB  - PURPOSE: Although an important risk factor for oral cancer is the presence of
      epithelial dysplasia, many lesions will not progress to malignancy. Matrix
      metalloproteinases (MMPs) are zinc-dependent proteinases capable of digesting
      various structural components of the extracellular matrix. Because MMPs are
      frequently overexpressed in oral squamous cell carcinoma (SCC), we hypothesized
      that they are also overexpressed in oral dysplasias; we also hypothesized that
      those dysplasias that progress to oral cancer express higher levels of MMPs than
      those lesions that do not progress. EXPERIMENTAL DESIGN: In this retrospective
      study, we examined changes in MMP-1, -2, and -9 mRNA expression using
      quantitative TaqMan reverse transcription-polymerase chain reaction in 34
      routinely processed oral dysplasias and 15 SCCs obtained from 34 patients. After
      several years of close follow-up, 19 dysplasias progressed to oral SCC and 15 did
      not. RESULTS: Overall, MMP-1 mRNA was overexpressed (>2-fold) in 24 of 34 (71%)
      dysplasias and 13 of 15 (87%) oral SCCs. MMP-2 overexpression was seen in 11 of
      34 (32%) dysplasias and 7 of 15 (47%) cancers; for MMP-9, overexpression was
      identified in 29 of 34 (85%) dysplasias and 15 of 15 (100%) cancers. MMP-1 and -9
      levels were significantly higher in the SCCs compared with all oral dysplasias (P
      = 0.004 and P = 0.01, respectively). MMP-1 and -9 mRNA levels were significantly
      higher in the oral dysplasias that progressed to oral cancer compared with those
      that did not (P = 0.04 and P = 0.002, respectively). CONCLUSIONS: Levels of MMP-1
      and -9 mRNA may be markers of malignant transformation of oral dysplasia to oral
      cancer.

PMID- 15475435
TI  - Modulation of DNA repair in vitro after treatment with chemotherapeutic agents by
      the epidermal growth factor receptor inhibitor gefitinib (ZD1839).
AB  - PURPOSE: The epidermal growth factor receptor (EGFR) is commonly expressed in
      human tumors and provides a target for therapy. Gefitinib (Iressa, ZD1839) is a
      quinazoline derivative that inhibits EGFR tyrosine kinase activity. Gefitinib
      demonstrated anticancer efficacy in vivo, and although experiments in vitro have
      suggested that inhibition of EGFR modulates the activity of chemotherapeutic
      agents, the mechanism of this interaction is unclear. We investigated mechanisms
      for this modulation. EXPERIMENTAL DESIGN: The antiproliferative effect of
      gefitinib alone or combined with cisplatin, melphalan, and etoposide was
      determined in a human breast (MCF-7) cancer cell line. Using the alkaline single
      cell gel electrophoresis (comet) assay, we investigated kinetics of DNA damage
      and repair after treatment with the chemotherapeutic drugs combined with
      gefitinib. To investigate whether the phosphatidylinositol 3'-kinase pathway was
      contributing to repair-inhibition produced by gefitinib, cells were exposed to
      chemotherapy in combination with the phosphatidylinositol 3'-kinase inhibitor
      LY294002. RESULTS: A superadditive (synergistic) increase in growth inhibition
      for combined treatment with gefitinib was found for cisplatin and etoposide, but
      not with melphalan. There was delayed repair of DNA strand breaks after treatment
      with etoposide combined with gefitinib, and repair of DNA interstrand cross-links
      produced by cisplatin is delayed in combination with gefitinib. Inhibition of
      cell proliferation and DNA repair was identical in cells treated with LY294002.
      Immunoprecipitation of cell extracts demonstrated that after exposure to
      gefitinib, there was an association between EGFR and DNA-PK(CS). CONCLUSION:
      Gefitinib acts through inhibition of repair of cisplatin and etoposide-induced
      DNA damage; this effect is mimicked by inhibitors of the phosphatidylinositol 3'
      kinase suggesting similar mechanisms of action.

PMID- 15475434
TI  - Leptin interferes with the effects of the antiestrogen ICI 182,780 in MCF-7
      breast cancer cells.
AB  - PURPOSE: Obesity is a risk factor for breast cancer development in postmenopausal
      women and correlates with shorter disease-free and overall survival in breast
      cancer patients, regardless of menopausal status. Adipose tissue is a major
      source of leptin, a cytokine regulating energy balance and controlling different
      processes in peripheral tissues, including breast cancer cell growth. Here, we
      investigated whether leptin can counteract antitumorigenic activities of the
      antiestrogen ICI 182,780 in breast cancer cells. EXPERIMENTAL DESIGN: Mitogenic
      response to leptin and the effects of leptin on ICI 182,780-dependent growth
      inhibition were studied in MCF-7 estrogen receptor alpha-positive breast cancer
      cells. The expression of leptin receptor and the activation of signaling pathways
      were studied by Western immunoblotting. The interference of leptin with ICI
      182,780-induced estrogen receptor alpha degradation was probed by Western
      immunoblotting, fluorescence microscopy, and pulse-chase experiments. Leptin
      effects on estrogen receptor alpha-dependent transcription in the presence and
      absence of ICI 182,780 were studied by luciferase reporter assays and chromatin
      immunoprecipitation. RESULTS: MCF-7 cells were found to express the leptin
      receptor and respond to leptin with cell growth and activation the signal
      transducers and activators of transcription 3, extracellular signal-regulated
      kinase-1/2, and Akt/GSK3/pRb pathways. The exposure of cells to 10 nmol/L ICI
      182,780 blocked cell proliferation, induced rapid estrogen receptor alpha
      degradation, inhibited nuclear estrogen receptor alpha expression, and reduced
      estrogen receptor alpha-dependent transcription from estrogen response element
      containing promoters. All of these effects of ICI 182,780 were significantly
      attenuated by simultaneous treatment of cells with 100 ng/mL leptin. CONCLUSIONS:
      Leptin interferes with the effects of ICI 182,780 on estrogen receptor alpha in
      breast cancer cells. Thus, high leptin levels in obese breast cancer patients
      might contribute to the development of antiestrogen resistance.

PMID- 15475436
TI  - Combined epidermal growth factor receptor targeting with the tyrosine kinase
      inhibitor gefitinib (ZD1839) and the monoclonal antibody cetuximab (IMC-C225):
      superiority over single-agent receptor targeting.
AB  - PURPOSE: The epidermal growth factor receptor (EGFR) is abnormally activated in
      cancer and two classes of anti-EGFR agents, monoclonal antibodies and low
      molecular-weight tyrosine kinase inhibitors, have shown antitumor activity in
      patients. Because these two classes of antireceptor agents target the EGFR at
      different sites, we decided to explore whether the combined administration of
      gefitinib, a tyrosine kinase inhibitor, and cetuximab, a monoclonal antibody, had
      superior antitumor activity than either agent given alone. EXPERIMENTAL DESIGN:
      We studied the effects of the combination of gefitinib and cetuximab in a panel
      of human cancer cell lines and in an EGFR-dependent human tumor xenograft model
      (A431). The effects of these two agents on EGFR signaling, proliferation,
      apoptosis, and vascularization were evaluated. In addition, we analyzed, with
      cDNA arrays, changes in gene expression profiles induced by both agents. RESULTS:
      The combined treatment with gefitinib and cetuximab resulted in a synergistic
      effect on cell proliferation and in superior inhibition of EGFR-dependent
      signaling and induction of apoptosis. In a series of in vivo experiments, single
      agent gefitinib or cetuximab resulted in transient complete tumor remission only
      at the highest doses. In contrast, suboptimal doses of gefitinib and cetuximab
      given together resulted in a complete and permanent regression of large tumors.
      In the combination-treated tumors, there was a superior inhibition of EGFR,
      mitogen-activated protein kinase, and Akt phosphorylation, as well as greater
      inhibition of cell proliferation and vascularization and enhanced apoptosis.
      Using cDNA arrays, we found 59 genes that were coregulated and 45 genes
      differentially regulated, including genes related to cell proliferation and
      differentiation, transcription, DNA synthesis and repair, angiogenesis, signaling
      molecules, cytoskeleton organization, and tumor invasion and metastasis.
      CONCLUSIONS: Our findings suggest both shared and complementary mechanisms of
      action with gefitinib and cetuximab and support combined EGFR targeting as a
      clinically exploitable strategy.

PMID- 15475437
TI  - A randomized phase IIb trial of pulmicort turbuhaler (budesonide) in people with
      dysplasia of the bronchial epithelium.
AB  - PURPOSE: Preclinical studies suggest that inhaled budesonide may be an effective
      chemopreventive agent for lung cancer. We conducted a phase IIb study to
      determine the effects of inhaled budesonide in smokers with bronchial dysplasia.
      EXPERIMENTAL DESIGN: A total of 112 smokers with more than or equal to one site
      of bronchial dysplasia > 1.2 mm in size identified by autofluorescence
      bronchoscopy-directed biopsy was randomly assigned to receive placebo or
      budesonide (Pulmicort Turbuhaler) 800 microg twice daily inhalation for 6 months.
      The primary end point was change in the histopathologic grade on repeat biopsy of
      the same sites at the end of 6 months. RESULTS: There were no significant
      differences in the regression or progression rates of bronchial dysplasia between
      the two groups. There was a statistically significant but modest decrease in p53
      and BclII expression in the bronchial biopsies after 6 months of Pulmicort
      Turbuhaler versus placebo (P = 0.01 and P = 0.001, respectively). There was a
      small but statistically significant decrease in the proportion of computed
      tomography-detected lung nodules after Pulmicort Turbuhaler compared with placebo
      (P = 0.024). CONCLUSIONS: Our results suggest that in smokers, inhaled budesonide
      in the dose of 1600 microg daily for 6 months had no effect in regression of
      bronchial dysplastic lesions or prevention of new lesions. Budesonide treatment
      resulted in a modest decrease in p53 and BclII protein expression in bronchial
      biopsies and a slightly higher rate of resolution of computed tomography-detected
      lung nodules. Whether budesonide truly has an effect in preneoplastic lesions in
      the peripheral airways and alveoli requires additional investigation.

PMID- 15475438
TI  - A phase I and pharmacokinetic study of Col-3 (Metastat), an oral tetracycline
      derivative with potent matrix metalloproteinase and antitumor properties.
AB  - PURPOSE: The purpose of this research was to assess the feasibility of
      administering Col-3, an oral chemically modified tetracycline derivative with
      potent inhibitory effects on matrix metalloproteinase activity and production,
      and recommend a dose on an uninterrupted once-daily schedule. The study also
      sought to characterize the pharmacokinetic behavior of Col-3 and seek evidence of
      anticancer activity. EXPERIMENTAL DESIGN: Patients with advanced solid
      malignancies were treated with escalating doses of Col-3 with dose level
      assignment according to an accelerated titration scheme. Because photosensitivity
      skin reactions were being reported in concurrent trials of Col-3, patients were
      instructed to apply sunscreen rigorously throughout the trial. The maximum
      tolerated dose was defined as the highest dose at which <2 of the first 6 new
      patients experienced dose-limiting toxicity. The pharmacokinetic behavior of Col
      3 was characterized, and pharmacodynamic relationships were sought. RESULTS:
      Thirty-three patients were treated with 73 courses of Col-3 at four dose levels
      ranging from 36 to 98 mg/m2/day. Unacceptably high incidences of photosensitivity
      skin reactions and malaise were noted in the first 28-day courses of patients
      treated with Col-3 at doses exceeding 50 mg/m2/day. At 50 mg/m2/day, severe
      toxicity occurred in 2 of 12 new patients in first courses, and no additional
      dose-limiting toxicities were observed in subsequent courses. Other mild to
      modest adverse effects included nausea, vomiting, liver function tests
      abnormalities, diarrhea, mucositis, leukopenia, and thrombocytopenia. The
      pharmacokinetics of Col-3 were dose proportional, and mean trough concentrations
      at steady state were similar to biologically relevant concentrations in
      preclinical studies. Major responses did not occur, but durable disease stability
      was noted in 3 patients, one each with carcinosarcoma of the uterus, pancreas,
      and ovary, all of whom had experienced disease progression before Col-3
      treatment. CONCLUSIONS: The recommended dose for Phase II studies of Col-3
      administered once daily on an uninterrupted schedule is 50 mg/m2/day accompanied
      by efforts that promote adherence to the use of sunscreen and other
      photoprotective measures. Pharmacokinetic results indicate that plasma
      concentrations above biologically relevant concentrations are readily maintained
      at this dose, and additional disease-directed studies, particularly in patients
      with soft tissue sarcoma, should be considered.

PMID- 15475439
TI  - Phase I trial of irinotecan, infusional 5-fluorouracil, and leucovorin (FOLFIRI)
      with erlotinib (OSI-774): early termination due to increased toxicities.
AB  - PURPOSE: This phase I study was conducted to establish the dose-limiting
      toxicities and maximum-tolerated dose of erlotinib, an oral epidermal growth
      factor receptor tyrosine kinase inhibitor, in combination with FOLFIRI, a
      standard regimen of irinotecan, leucovorin, and infusional 5-fluorouracil (5-FU)
      in patients with advanced colorectal cancer. EXPERIMENTAL DESIGN: The trial used
      a dose-escalation design beginning with 100 mg/day erlotinib continuously and
      dose-reduced FOLFIRI (150 mg/m2 i.v. day 1 irinotecan, 200 mg/m2 i.v. leucovorin,
      320 mg/m2 i.v. bolus days 1 to 2 5-FU, and 480 mg/m2 i.v. 5-FU infusion over 22
      hours, days 1 to 2) administered in 6-week cycles (three FOLFIRI treatments).
      Plasma sampling was performed for irinotecan, erlotinib, and 5-FU for
      pharmacokinetic analysis during cycle 1. RESULTS: The study was halted after six
      patients at the lowest dose level due to unexpectedly severe toxicities,
      including disfiguring grade 2 rash (three patients), grade 3 diarrhea (three
      patients), and grade > or = 3 neutropenia (three patients). All patients required
      some dose interruption or reduction of either erlotinib or FOLFIRI, and only one
      patient completed two 6-week cycles of therapy. Five patients had stable disease
      after one cycle, and one patient had a partial response. No plasma
      pharmacokinetic interaction was observed that could explain the observed
      increased toxicity. CONCLUSIONS: FOLFIRI combined with erlotinib causes excessive
      toxicity at reduced doses. These findings contrast with available data regarding
      the optimal safety profile of trials combining small molecule epidermal growth
      factor receptor inhibitors with other conventional chemotherapy and highlight the
      need to perform safety-oriented studies of such combinations.

PMID- 15475440
TI  - A phase II study of etanercept (Enbrel), a tumor necrosis factor alpha inhibitor
      in patients with metastatic breast cancer.
AB  - PURPOSE: Tumor necrosis factor (TNF) alpha is a key player in the tumor
      microenvironment and is involved in the pathogenesis of breast cancer. Etanercept
      is a recombinant human soluble p75 TNF receptor that binds to TNF-alpha and
      renders it biologically unavailable. In the current study, we sought to determine
      the toxicity, biological activity, and therapeutic efficacy of Etanercept in
      metastatic breast cancer. EXPERIMENTAL DESIGN: We initiated a Phase II,
      nonrandomized, open-labeled study in patients with progressive metastatic breast
      cancer refractory to conventional therapy (Phase I toxicity data were available
      in patients with rheumatoid arthritis). Etanercept was administered
      subcutaneously at a dose of 25 mg twice weekly until disease progression.
      RESULTS: Sixteen patients were recruited [median age 53 years (range, 34 to 74)].
      A total of 141.6 weeks of therapy was administered (median of 8.1 weeks). Seven
      patients received > or =12 weeks of therapy. The most common side effects were
      injection site reactions (6), fatigue (5), loss of appetite (2), nausea (1),
      headache (1), and dizziness (1). Brief period of disease stabilization was seen
      in 1 patient lasting for 16.4 weeks. Immunoreactive TNF-alpha was elevated within
      24 hours of therapy and persisted until the end of treatment (days 7, 28, 56, and
      84). Phytohemagglutinin stimulates the production of interleukin-6 and CCL2 in
      peripheral blood cells, and the ability of Etanercept to modulate this response
      was assessed in a cytokine release assay. A consistent decrease in interleukin-6
      and CCL2 level was seen compared with pretreatment values in serial blood samples
      (days 1, 7, 28, 56, and 84). CONCLUSIONS: Our study shows the safety and
      biological activity of Etanercept in breast cancer and provides data to assess
      pharmacodynamic endpoints of different schedules of Etanercept and combinations
      with chemotherapy or other biological therapies.

PMID- 15475441
TI  - No long-term increase in sperm aneuploidy rates after anticancer therapy: sperm
      fluorescence in situ hybridization analysis in 26 patients treated for testicular
      cancer or lymphoma.
AB  - PURPOSE: Lymphomas and testicular cancers are the most frequent malignancies
      among young men. With recent improvement of survival rates, for many patients,
      the question is raised of the consequences of the anticancer treatments on their
      fertility and more specifically of a potential genetic risk for the offspring.
      This article presents the study of sperm aneuploidy rates in the largest
      population of cancer-treated patients studied thus far. EXPERIMENTAL DESIGN: In
      the present study, 38 patients were initially included 7 months to 5 years after
      a cancer treatment by chemotherapy and/or radiotherapy for testicular cancer (n =
      19) or lymphoma (n = 19). Twelve of them were azoospermic. Sperm aneuploidy rates
      of chromosomes X, Y, 13, 18, and 21 were analyzed by multicolor fluorescent in
      situ hybridization in the 26 other patients. RESULTS: In most cases, the
      disomy/diploidy rates after cancer therapy did not significantly differ from
      those observed in the group of control healthy donors. Only five patients (one
      lymphoma and four testicular cancer) showed significant but still moderate
      increases in disomic and/or diploid sperm. For the lymphoma patient, the short
      posttherapeutic delay after the treatment could explain the elevated aneuploidy
      rates, whereas no risk factor in the clinical, biological, or therapeutic records
      could be identified in any of the four testicular cancer patients with elevated
      sperm aneuploidy rates. CONCLUSIONS: These data suggest an absence of long-term
      effect of anticancer therapy on sperm aneuploidy rates, and therefore, no long
      term increased risk of aneuploidy for the offspring obtained either spontaneously
      or after assisted reproductive techniques.

PMID- 15475442
TI  - The spermatozoa protein, SLLP1, is a novel cancer-testis antigen in hematologic
      malignancies.
AB  - PURPOSE: Neoplastic cells often aberrantly express normal testicular proteins.
      Because these proteins have a very restricted normal tissue expression, they may
      be suitable targets for immunotherapy. SLLP1 is an intra-acrosomal,
      nonbacteriolytic, c lysozyme-like protein recently isolated from human
      spermatozoa. In this study, we determined whether SLLP1 is a novel cancer-testis
      antigen in hematologic malignancies EXPERIMENTAL DESIGN: SLLP1 expression in
      hematologic tumor cells and normal tissues was determined using a combination of
      reverse transcription-PCR, real-time PCR, and Western blot analysis. The presence
      of antibodies against SLLP1 was determined by ELISA analysis. RESULTS: SLLP1 was
      aberrantly expressed in the tumor cells from 2 of 9 acute myeloid leukemia, 3 of
      11 chronic lymphocytic leukemia, 4 of 14 chronic myeloid leukemia, and 6 of 17
      multiple myeloma. In contrast, they were not detected in corresponding specimens
      from any healthy donors. SLLP1 exhibited a very restricted normal tissue
      expression, being found only in testis/spermatozoa. SLLP1 was expressed in some
      tumor cells at a level of >25%. High titer IgG antibodies against SLLP1 were also
      detected in the sera of some of these patients. CONCLUSIONS: SLLP1 is a novel
      cancer-testis antigen in hematologic malignancies and is capable of eliciting B
      cell immune responses in vivo in cancer-bearing individuals. Our results,
      therefore, support SLLP1 as a protein target appropriate for additional in vitro
      study to define its suitability for immunotherapy.

PMID- 15475443
TI  - NY-ESO-1 expression and immunogenicity in esophageal cancer.
AB  - PURPOSE: Although NY-ESO-1 was isolated from an esophageal carcinoma patient, its
      expression in this type of cancer and its immunogenicity in esophageal cancer
      patients have not yet been fully elucidated. We report here the frequency of NY
      ESO-1 mRNA and protein expression in esophageal cancer and the presence of NY-ESO
      1-specific immune response in patients. EXPERIMENTAL DESIGN: One hundred twenty
      three esophageal squamous cell carcinoma specimens were analyzed for the
      expression of NY-ESO-1 mRNA by conventional and real-time reverse transcription
      PCR and the expression of protein by immunohistochemistry and Western blot. Sera
      and peripheral blood lymphocytes from 51 patients were analyzed for the NY-ESO-1
      antibody production by enzyme-linked immunosorbent assay and NY-ESO-1 T cell
      response by enzyme-linked immunospot assay. Survival analyses were also
      performed. RESULTS: NY-ESO-1 mRNA was expressed in 41 of 123 (33%) esophageal
      squamous cell carcinoma specimens, and its expression was found at higher
      frequency in well-differentiated and moderately differentiated type of cancer. No
      mRNA copy was detected in any of the adjacent normal tissues. Twenty-one of 24
      (87.5%) NY-ESO-1 mRNA-positive tumors were stained positively by
      immunohistochemistry. Correlation between the level of NY-ESO-1 mRNA expression
      and the degree of immunohistochemistry positivity was observed. Antibody
      production was observed in 2 patients with tumors that showed protein expression.
      Furthermore, a CD8 T-cell response against NY-ESO-1 was observed in 1 of the 2
      seropositive patients. CONCLUSIONS: The high expression frequency of NY-ESO-1
      mRNA and protein indicates NY-ESO-1 as a feasible vaccine target in esophageal
      cancer.

PMID- 15475444
TI  - Expression of the tumor suppressor gene ARHI in epithelial ovarian cancer is
      associated with increased expression of p21WAF1/CIP1 and prolonged progression
      free survival.
AB  - PURPOSE: ARHI, an imprinted putative tumor suppressor gene, is expressed in
      normal ovarian epithelial cells, but its expression is down-regulated or lost in
      most ovarian cancer cell lines. Reexpression of ARHI in cancer cells induces
      p21(WAF1/CIP1), down-regulates cyclin D1 promoter activity and inhibits growth in
      cell culture and in heterografts. To determine the relevance of these
      observations to clinical cancer, we have now measured ARHI expression in normal,
      benign and malignant ovarian tissues using immunohistochemistry and in situ
      hybridization. EXPERIMENTAL DESIGN: Paraffin embedded tissues from 7 normal
      ovaries, 22 cystadenomas and 42 borderline lesions were analyzed using standard
      immunoperoxidase and in situ hybridization techniques to assess ARHI expression.
      In addition, immunohistochemistry against ARHI was performed on a tissue
      microarray containing 441 consecutive cases of ovarian carcinoma. RESULTS: Strong
      ARHI expression was found in normal ovarian surface epithelial cells, cysts and
      follicles using immunohistochemistry and in situ hybridization. Reduced ARHI
      expression was observed in tumors of low malignant potential as well as in
      invasive cancers. ARHI expression was down-regulated in 63% of invasive ovarian
      cancer specimens and could not be detected in 47%. When immunohistochemistry and
      in situ hybridization were compared, ARHI protein expression could be down
      regulated in the presence of ARHI mRNA. ARHI expression was correlated with
      expression of p21(WAF1/CIP1) (P = 0.0074) but not with cyclin D1 and associated
      with prolonged disease free survival (P = 0.001). On multivariate analysis, ARHI
      expression, grade and stage were independent prognostic factors. ARHI expression
      did not correlate with overall survival. CONCLUSIONS: Persistence of ARHI
      expression in epithelial ovarian cancers correlated with prolonged disease free
      survival and expression of the cyclin dependent kinase inhibitor p21(WAF1/CIP1).

PMID- 15475445
TI  - Expression of hypoxia-related tissue factors correlates with diminished survival
      of adjuvantly treated patients with chromosome 1p aberrant oligodendroglial
      neoplasms and therapeutic implications.
AB  - PURPOSE: Oligodendroglial neoplasms with chromosome 1p deletion are
      chemosensitive, and stratified adjuvant therapies have been proposed on the basis
      of 1p status. In this study, we evaluated expression of hypoxia-related factors
      and its influence on survival in oligodendroglial brain tumors with chromosome 1p
      aberrations. EXPERIMENTAL DESIGN: Forty-four primary and 16 recurrent
      oligodendroglial neoplasms with 1p aberrations (deletion or imbalance) were
      investigated immunohistochemically for expression of hypoxia-inducible factor
      1alpha and carbonic anhydrase-9. We used in situ hybridization to investigate
      expression of vascular endothelial growth factor-mRNA. We defined as "low hypoxia
      score" expression of no or only one marker and as "high hypoxia score" expression
      of two or three markers. The predominant vascular patterns of tumors were defined
      as classic or bizarre vascular formations, based on anti-CD34-immunostaining.
      RESULTS: High hypoxia score was evident in 16 of 44 (36.4%) primary tumor
      specimens and in 14 of 16 (87.5%) recurrent tumors (P = 0.001). High hypoxia
      score was associated with the presence of bizarre vascular proliferations and WHO
      grade III. In the subgroup of patients who received adjuvant therapy, univariate
      analysis showed significantly shorter survival of patients with high hypoxia
      score (n = 27; P = 0.0145). For all of the primary tumors, hypoxia score was an
      independent prognostic factor (P = 0.045). CONCLUSIONS: A fraction of
      oligodendroglial neoplasms with 1p aberrations shows evidence of tissue hypoxia,
      which significantly influences survival of patients receiving adjuvant therapy.
      Evaluation of tissue hypoxia could become useful for recruitment of patients for
      individualized therapy strategies, e.g., selection of patients with hypoxic
      tumors for hyperbaric oxygenation preceding radiotherapy.

PMID- 15475446
TI  - High levels of phosphorylated form of Akt-1 in prostate cancer and non-neoplastic
      prostate tissues are strong predictors of biochemical recurrence.
AB  - Akt is a serine-threonine-kinase that phosphorylates proteins in several pathways
      regulating aspects of metabolism, apoptosis, and proliferation. Akt signaling
      promotes proliferation and increased cell survival and is thought to play an
      important role in prostate cancer progression. Tissue microarrays (640 patients)
      with triplicate cores of non-neoplastic prostate, BPH, and index tumor were
      immunostained with antibody to Phospho-Akt (Ser473), digitized, and quantified.
      The expression index (Intensity*Percentage) was used for statistical analysis. P
      Akt-1 staining was found in both the non-neoplastic and cancer tissues,
      predominantly in cytoplasmic locations. High level P-Akt-1 is expressed almost
      exclusively in cancer. By Kaplan-Meier actuarial model, high expression of P-Akt
      1 in prostate cancer was predictive of a higher probability of recurrence on
      univariate and multivariate analysis. Akt-1 expression was an independent
      prognostic indicator of biochemical recurrence-free survival when Gleason 6 and 7
      patients were analyzed separately. Surprisingly, a high level of P-Akt-1
      expression in non-neoplastic tissues is also an independent predictor of
      biochemical recurrence. This suggests that some patients might have an inherent
      predisposition to express a high level of P-Akt-1 and, therefore, to have an
      adverse prognosis. We conclude that P-Akt-1 is most likely involved in the
      progression of prostate cancer and is an excellent biomarker for biochemical
      recurrence.

PMID- 15475447
TI  - Matrix metalloproteinase-2 status in stromal fibroblasts, not in tumor cells, is
      a significant prognostic factor in non-small-cell lung cancer.
AB  - PURPOSE: The purpose is to assess clinical significance of matrix
      metalloproteinase (MMP)-2 and MMP-9 status, especially MMP-2 status, in stromal
      cells in non-small-cell lung cancer (NSCLC) because experimental studies have
      revealed that stromal MMP-2 plays important roles in progression of malignant
      tumors, but most clinical studies focused on tumoral MMP-2 expression, not
      stromal MMP-2 expression. EXPERIMENTAL DESIGN: We conducted a retrospective study
      on MMP-2 and MMP-9 expression as evaluated immunohistochemically in a total of
      218 consecutive patients with completely resected pathological stage I-IIIA,
      NSCLC. RESULTS: Strong MMP-2 expression in tumor cells and stromal fibroblasts
      were documented in 54 (24.8%) and 132 (60.6%) patients, respectively. Strong MMP
      2 expression in stromal fibroblasts was more frequently seen in squamous cell
      carcinoma (72.7%) than in adenocarcinoma (54.9%; P = 0.016). Tumors showing
      strong MMP-2 expression in stromal fibroblasts showed a significantly higher
      intratumoral microvessel density (IMVD) than weak stromal MMP-2 tumors (mean
      intratumoral microvessel density, 50.9 versus 32.4, P = 0.003). In addition,
      postoperative prognosis of strong stromal MMP-2 patients was significantly poorer
      than that of weak stromal MMP-2 patients (5-year survival rate, 77.5 versus
      60.2%, P = 0.032), and the prognostic significance was enhanced in squamous cell
      carcinoma patients but disappeared in adenocarcinoma patients. Multivariate
      analyses confirmed that strong stromal MMP-2 expression was a significant factor
      to predict a poor prognosis in squamous cell carcinoma patients, not in
      adenocarcinoma patients. In contrast, MMP-2 or MMP-9 status in tumor cells was
      not a significant prognostic factor. CONCLUSIONS: MMP-2 status in stromal
      fibroblasts, not in tumor cells, was a significant prognostic factor associated
      with angiogenesis in NSCLC.

PMID- 15475448
TI  - Gene expression profiling of differentiated thyroid neoplasms: diagnostic and
      clinical implications.
AB  - PURPOSE: The purpose of this research was to identify novel genes that can be
      targeted as diagnostic and clinical markers of differentiated thyroid tumors.
      EXPERIMENTAL DESIGN: Gene expression analysis using microarray platform was
      performed on 6 pathologically normal thyroid samples and 12 primary follicular
      and papillary thyroid neoplasms. Microarrays containing probes for 5,760 human
      full-length cDNAs were used for hybridization with total RNA from normal and
      tumor thyroid samples labeled with Cy3-dUTP and Cy5-dUTP, respectively. Scanned
      array images were recorded, and data analysis was performed. Selected sets of
      differentially expressed genes were analyzed using quantitative real-time reverse
      transcription-PCR for verification. RESULTS: We identified 155 genes that
      differentiate histologically normal thyroid tissues from benign and malignant
      thyroid neoplasms. Of these 75 genes were differentiated between follicular
      neoplasms (adenoma and carcinoma) and the follicular variant of papillary
      carcinoma. Purely follicular neoplasms (adenomas and carcinomas) shared many
      genetic profiles, and only 43 genes were distinctly different between these
      tumors. Hierarchical cluster analysis also differentiated conventional papillary
      carcinoma from its follicular variant and follicular tumors. The differentially
      expressed genes were composed of members of cell differentiation, adhesion,
      immune response, and proliferation associated pathways. Quantitative real-time
      reverse transcription-PCR analysis of selected genes corroborated the microarray
      expression results. CONCLUSIONS: Our study show the following: (1) differences in
      gene expression between tumor and nontumor bearing normal thyroid tissue can be
      identified, (2) a set of genes differentiate follicular neoplasm from follicular
      variant of papillary carcinoma, (3) follicular adenoma and carcinoma share many
      of the differentiated genes, and (4) gene expression differences identify
      conventional papillary carcinoma from the follicular variant.

PMID- 15475449
TI  - Overexpression of G1-S cyclins and cyclin-dependent kinases during multistage
      human pancreatic duct cell carcinogenesis.
AB  - PURPOSE: Molecular analysis of pancreatic intraepithelial neoplasia lesions and
      ductal adenocarcinoma suggested a multistage paradigm for pancreatic duct cell
      carcinogenesis. This study investigated the molecular basis for the neoplastic
      duct cells in this pancreatic intraepithelial neoplasia-carcinoma sequence to
      acquire progressive enhancement of their proliferative potential. EXPERIMENTAL
      DESIGN: Using tissue microarray blocks containing 15 to 40 pancreatic
      intraepithelial neoplasia lesions and ductal adenocarcinoma of pancreas, we
      studied by immunohistochemistry the expression profiles of cyclins and cyclin
      dependent kinases (CDKs) that regulate the G1-S cell cycle checkpoints. The role
      of cyclins D3 and D1 in three pancreatic cancer cell lines was investigated using
      specific short interfering RNA technique. RESULTS: Cyclin D3 overexpression was
      noted the earliest in pancreatic intraepithelial neoplasia-1A and was prevalent
      in 90% to 100% of high-grade pancreatic intraepithelial neoplasias and ductal
      cancer. Cyclin A overexpression was also noted early and reached 50% to 100% of
      high-grade pancreatic intraepithelial neoplasias and cancer, but the percentage
      of abnormal duct cells showing overexpression of cyclin A was significantly lower
      than cyclin D3. Cyclin E overexpression occurred in 20% to 25% of high-grade
      pancreatic intraepithelial neoplasias and in 75% of ductal carcinoma. Cyclin D1
      demonstrated the lowest frequency of overexpression that occurred late. CDK2 and
      CDK4 overexpression was also noted in early pancreatic intraepithelial neoplasias
      and progressively increased to reach 60% to 75% in carcinoma. The down-regulation
      of cyclin D3 mRNA and protein levels using specific short interfering RNA
      resulted in growth inhibition of pancreatic cancer cell lines. CONCLUSION: The
      results provide additional insight into the mechanism of G1-S cell cycle
      checkpoints deregulation during stepwise pancreatic duct cell carcinogenesis, and
      suggest a p16-independent role for cyclin D3 in deregulating the G1 cell cycle
      checkpoints during early stages of pancreatic duct cell carcinogenesis.

PMID- 15475450
TI  - CD74 is expressed by multiple myeloma and is a promising target for therapy.
AB  - PURPOSE: CD74 (HLA-DR-associated invariant chain) plays a role in antigen
      presentation. In addition to its expression on antigen-presenting cells, it is
      expressed by carcinomas of renal, lung, gastric, and thymic origin and by certain
      sarcomas. The restricted expression of CD74 by normal tissues and its very rapid
      internalization make CD74 an attractive therapeutic target for both cancer and
      immunologic diseases. Preclinical efficacy of anti-CD74 monoclonal antibody (mAb)
      therapy has been demonstrated in B-lymphoma models. Because there are few
      validated antigenic targets in multiple myeloma, CD74 expression was examined.
      EXPERIMENTAL DESIGN: CD74 expression was assessed by immunohistochemistry in bone
      marrow biopsies of known multiple myeloma cases. Its expression was measured by
      flow cytometry in multiple myeloma lines, and CD74 mRNA expression was determined
      by reverse transcription-PCR. In addition, the in vitro antiproliferative effect
      of LL1 mAb was evaluated on a CD74+ multiple myeloma cell line using a
      [3H]thymidine incorporation assay. RESULTS: CD74 expression was observed in 19 of
      22 cases of multiple myeloma, with most expressing moderate to high levels in the
      majority of malignant plasma cells. CD74 was expressed by most multiple myeloma
      cell lines, as was CD74 mRNA, at levels mirroring CD74 protein. Also, unlabeled
      LL1 mAb mediated in vitro growth inhibition of a CD74+ multiple myeloma cell
      line. CONCLUSIONS: CD74 expression is frequent in multiple myeloma, with
      predominant expression by the malignant plasma cells. Because anti-CD74 mAbs
      internalize very rapidly and LL1 mAb has shown efficacy in B-lymphoma models,
      CD74 represents a novel and promising target for treatment of multiple myeloma.
      Therefore, LL1 mAb is well suited as a carrier of radionuclides, drugs, or
      toxins, and also has activity as an unlabeled mAb, thereby supporting its
      development for this unmet need in cancer therapy.

PMID- 15475451
TI  - Identification of glypican-3 as a novel tumor marker for melanoma.
AB  - PURPOSE: We reported recently the novel tumor marker glypican-3 (GPC3) for
      hepatocellular carcinoma. In the present study, we investigated the expression of
      GPC3 in human melanoma cell lines and tissues and asked whether GPC3 could be a
      novel tumor marker for melanoma. EXPERIMENTAL DESIGN: Expression of GPC3 mRNA and
      protein was investigated in human melanoma cell lines and tissues using reverse
      transcription-PCR and immunohistochemical analysis. Secreted GPC3 protein was
      quantified using ELISA in culture supernatants of melanoma cell lines and in sera
      from 91 patients with melanoma and 28 disease-free patients after surgical
      removal of primary melanoma. All of the subjects were Japanese nationals.
      RESULTS: In >80% of melanoma and melanocytic nevus, there was evident expression
      of GPC3 mRNA and protein. Furthermore, GPC3 protein was evidenced in sera of
      39.6% (36 of 91) of melanoma patients but not in sera from subjects with large
      congenital melanocytic nevus (0 of 5) and from healthy donors (0 of 60). Twenty
      seven of 36 serum GPC3-positive patients were negative for both serum 5-S
      cysteinyldopa and melanoma-inhibitory activity, well-known tumor markers for
      melanoma. The positive rate of serum GPC3 (39.6%) was significantly higher than
      that of 5-S-cysteinyldopa (26.7%) and of melanoma-inhibitory activity (20.9%).
      Surprisingly, we detected serum GPC3 even in patients with stage 0 in situ
      melanoma. The positive rate of serum GPC3 at stage 0, I, and II (44.4%, 40.0%,
      and 47.6%) was significantly higher than that of 5-S-cysteinyldopa (0.0%, 8.0%,
      and 10.0%). Also observed was the disappearance of GPC3 protein in sera from 11
      patients after surgical removal of the melanoma. CONCLUSIONS: GPC3 is apparently
      a novel tumor marker useful for the diagnosis of melanoma, especially in early
      stages of the disorder.

PMID- 15475452
TI  - Chemotherapy is more effective in patients with breast cancer not expressing
      steroid hormone receptors: a study of preoperative treatment.
AB  - PURPOSE: The purpose of this research was to identify factors predicting response
      to preoperative chemotherapy. EXPERIMENTAL DESIGN: In a large volume laboratory
      using standard immunohistochemical methods, we reviewed the pretreatment biopsies
      and histologic specimens at final surgery of 399 patients with large or locally
      advanced breast cancer (cT2-T4, N0-2, M0) who were treated with preoperative
      chemotherapy. The incidence of pathological complete remission and the incidence
      of node-negative status at final surgery were assessed with respect to initial
      pathological and clinical findings. Menopausal status, estrogen receptor status,
      progesterone receptor status [absent (0% of the cells positive) versus
      expressed], clinical tumor size, histologic grade, Ki-67, Her-2/neu expression,
      and type and route of chemotherapy were considered. RESULTS: High rates of
      pathological complete remission were associated with absence of estrogen receptor
      and progesterone receptor expression (P < 0.0001), and grade 3 (P = 0.001).
      Significant predictors of node-negative status at surgery were absence of
      estrogen receptor and progesterone receptor expression (P < 0.0001), clinical
      tumor size <5 cm (P < 0.001), and use of infusional regimens (P = 0.003). The
      chance of obtaining pathological complete remission or node-negative status for
      patients with endocrine nonresponsive tumors compared with those having some
      estrogen receptor or progesterone receptor expression was 4.22 (95% confidence
      interval, 2.20-8.09, 33.3% versus 7.5%) and 3.47 (95% confidence interval, 2.09
      5.76, 42.9% versus 21.7%), respectively. Despite the significantly higher
      incidence of pathological complete remission and node-negative status achieved by
      preoperative chemotherapy for patients with estrogen receptor and progesterone
      receptor absent disease, the disease-free survival was significantly worse for
      this cohort compared with the low/positive expression cohort (4-year disease-free
      survival %: 41% versus 74%; hazard ratio 3.22; 95% confidence interval, 2.28
      4.54; P < 0.0001). CONCLUSIONS: Response to preoperative chemotherapy is
      significantly higher for patients with endocrine nonresponsive tumors. New
      chemotherapy regimens or combinations should be explored in this cohort of
      patients with poor outcome. For patients with endocrine responsive disease, the
      role of preoperative endocrine therapies should be studied.

PMID- 15475453
TI  - Loss of parafibromin immunoreactivity is a distinguishing feature of parathyroid
      carcinoma.
AB  - PURPOSE: A reliable method for diagnosing parathyroid carcinoma has remained
      elusive over the years, resulting in its under-recognition and suboptimal
      therapy. Obtaining an accurate diagnosis has become an even more pressing matter
      with recent evidence that germline HRPT2 gene mutations are found in patients
      with apparently sporadic parathyroid carcinoma. There is a high prevalence of
      HRPT2 gene mutations and biallelic inactivation in parathyroid carcinoma. We
      hypothesize that loss of parafibromin, the protein product of the HRPT2 gene,
      would distinguish carcinoma from benign tissue. EXPERIMENTAL DESIGN: We generated
      a novel antiparafibromin monoclonal antibody and performed immunostaining on 52
      definite carcinoma specimens, 6 equivocal carcinoma specimens, 88 benign
      specimens, and 9 hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas
      from patients with primary hyperparathyroidism from nine worldwide centers and
      one national database. RESULTS: We report that the loss of parafibromin nuclear
      immunoreactivity has 96% sensitivity [95% confidence interval (CI), 85-99%] and
      99% specificity (95% CI, 92-100%) in diagnosing definite carcinoma. Inter
      observer agreement for evaluation of parafibromin loss was excellent, with
      unweighted kappa of 0.89 (95% CI, 0.79-0.98). Two equivocal carcinomas
      misclassified as adenomas were highlighted by parafibromin immunostaining. One of
      these tumors has since recurred, satisfying criteria for a definite carcinoma.
      Similarly, eight of nine HPT-JT syndrome-related adenomas showed absent nuclear
      immunoreactivity. CONCLUSIONS: Parafibromin is a promising molecular marker for
      diagnosing parathyroid carcinoma. The similar loss of parafibromin
      immunoreactivity in HPT-JT syndrome-related adenomas suggests that this is a
      pivotal step in parathyroid tumorigenesis.

PMID- 15475454
TI  - Liposomal irinotecan: formulation development and therapeutic assessment in
      murine xenograft models of colorectal cancer.
AB  - PURPOSE: The purpose is to demonstrate whether an appropriately designed
      liposomal formulation of irinotecan is effective in treating mice with liver
      localized colorectal carcinomas. EXPERIMENTAL DESIGN: Irinotecan was encapsulated
      in 1,2-distearoyl-sn-glycero-3-phosphocholine/cholesterol (55:45 molar ratio)
      liposomes using an ionophore (A23187)-generated transmembrane proton gradient.
      This formulation was evaluated in vivo by measuring plasma elimination of
      liposomal lipid and drug after i.v. administration. Therapeutic activity was
      determined in SCID/Rag-2M mice bearing s.c. LS180 tumors or orthotopic LS174T
      colorectal metastases. RESULTS: Drug elimination from the plasma was
      significantly reduced when irinotecan was administered in the liposomal
      formulation. At 1 hour after i.v. administration, circulating levels of the
      liposomal drug were 100-fold greater than that of irinotecan given at the same
      dose. High-performance liquid chromatographic analysis of plasma samples
      indicated that liposomal irinotecan was protected from inactivating hydrolysis to
      the carboxylate form. This formulation exhibited substantially improved
      therapeutic effects. For the LS180 solid tumor model, it was shown that after a
      single injection of liposomal irinotecan at 50 mg/kg, the time to progress to a
      400-mg tumor was 34 days (as compared with 22 days for animals treated with free
      drug at an equivalent dose). In the model of colorectal liver metastases
      (LS174T), a median survival time of 79 days was observed after treatment with
      liposomal irinotecan (50 mg/kg, given every 4 days for a total of three doses).
      Saline and free drug treated mice survived for 34 and 53 days, respectively.
      CONCLUSIONS: These results illustrate that liposomal encapsulation can
      substantially enhance the therapeutic activity of irinotecan and emphasize the
      potential for using liposomal irinotecan to treat liver metastases.

PMID- 15475455
TI  - Influence of casein kinase II in tumor necrosis factor-related apoptosis-inducing
      ligand-induced apoptosis in human rhabdomyosarcoma cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis
      via the death receptors DR4 and DR5 in transformed cells in vitro and exhibits
      potent antitumor activity in vivo with minor side effects. Protein kinase casein
      kinase II (CK2) is increased in response to diverse growth stimuli and is
      aberrantly elevated in a variety of human cancers. Rhabdomyosarcoma tumors are
      the most common soft-tissue sarcoma in childhood. In this investigation, we
      demonstrate that CK2 is a key survival factor that protects tumor cells from
      TRAIL-induced apoptosis. We have demonstrated that inhibition of CK2
      phosphorylation events by 5,6-dichlorobenzimidazole (DRB) resulted in dramatic
      sensitization of tumor cells to TRAIL-induced apoptosis. CK2 inhibition also
      induced rapid cleavage of caspase-8, -9, and -3, as well as the caspase substrate
      poly(ADP-ribose) polymerase after TRAIL treatment. Overexpression of Bcl-2
      protected cells from TRAIL-induced apoptosis in the presence of the CK2
      inhibitor. Death signaling by TRAIL in these cells was Fas-associated death
      domain and caspase dependent because dominant negative Fas-associated death
      domain or the cowpox interleukin 1beta-converting enzyme inhibitor protein
      cytokine response modifier A prevented apoptosis in the presence of DRB. Analysis
      of death-inducing signaling complex (DISC) formation demonstrated that inhibition
      of CK2 by DRB increased the level of recruitment of procaspase-8 to the DISC and
      enhanced caspase-8-mediated cleavage of Bid, thereby increasing the release of
      the proapoptotic factors cytochrome c, HtrA2/Omi, Smac/DIABLO, and apoptosis
      inducing factor (AIF) from the mitochondria, with subsequent degradation of X
      linked inhibitor of apoptosis protein (XIAP). To further interfere with CK2
      function, JR1 and Rh30 cells were transfected with either short hairpin RNA
      targeted to CK2alpha or kinase-inactive CK2alpha (K68M) or CK2alpha' (K69M). Data
      show that the CK2 kinase activity was abrogated and that TRAIL sensitivity in
      both cell lines was increased. Silencing of CK2alpha expression with short
      hairpin RNA was also associated with degradation of XIAP. These findings suggest
      that CK2 regulates TRAIL signaling in rhabdomyosarcoma by modulating TRAIL
      induced DISC formation and XIAP expression.

PMID- 15475456
TI  - Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR
      ABL-positive cells.
AB  - The therapeutic efficacy of imatinib mesylate (Gleevec) is based on its specific
      inhibition of the BCR-ABL oncogene protein, a widely expressed tyrosine kinase in
      chronic myelogenous leukemia (CML) cells. The goal of this study was to evaluate
      glucose metabolism in BCR-ABL-positive cells that are sensitive to imatinib
      exposure. Two human BCR-ABL-positive cell lines (CML-T1 and K562) and one BCR-ABL
      negative cell line (HC-1) were incubated with different imatinib concentrations
      for 96 hours. Magnetic resonance spectroscopy on cell acid extracts was performed
      to evaluate [1-13C]glucose metabolism, energy state, and changes in endogenous
      metabolites after incubation with imatinib. Imatinib induced a concentration
      dependent inhibition of cell proliferation in CML-T1 (IC50, 0.69 +/- 0.06
      micromol/L) and K562 cells (IC50, 0.47 +/- 0.04 micromol/L), but not in HC-1
      cells. There were no metabolic changes in imatinib-treated HC-1 cells. In BCR-ABL
      positive cells, the relevant therapeutic concentrations of imatinib (0.1-1.0
      micromol/L) decreased glucose uptake from the media by suppressing glycolytic
      cell activity (C3-lactate at 0.25 mmol/L, 65% for K562 and 77% for CML-T1 versus
      control). Additionally, the activity of the mitochondrial Krebs cycle was
      increased (C4-glutamate at 0.25 micromol/L, 147% for K562 and 170% for CML-T1).
      The improvement in mitochondrial glucose metabolism resulted in an increased
      energy state (nucleoside triphosphate/nucleoside diphosphate at 0.25 micromol/L,
      130% for K562 and 125% for CML-T1). Apoptosis was observed at higher
      concentrations. Unlike standard chemotherapeutics, imatinib, without cytocidal
      activity, reverses the Warburg effect in BCR-ABL-positive cells by switching from
      glycolysis to mitochondrial glucose metabolism, resulting in decreased glucose
      uptake and higher energy state.

PMID- 15475457
TI  - Distribution of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) uracil in mice
      bearing colorectal cancer xenografts: rationale for therapeutic use and as a
      positron emission tomography probe for thymidylate synthase.
AB  - PURPOSE: In colorectal, breast, and head and neck cancers, response to 5
      fluorouracil is associated with low expression of thymidylate synthase. In
      contrast, tumors with high expression of thymidylate synthase may be more
      sensitive to prodrugs such as 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) uracil
      (FAU) that are activated by thymidylate synthase. These studies were designed to
      evaluate FAU as a potential therapeutic and diagnostic probe. EXPERIMENTAL
      DESIGN: [18F]-FAU and [3H]-FAU were synthesized with >97% radiochemical purity.
      [3H]-FAU or [18F]-FAU was administered intravenously to severe combined
      immunodeficient mice bearing either HT29 (low thymidylate synthase) or LS174T
      (high thymidylate synthase) human colon cancer xenografts. Four hours after [3H]
      FAU dosing, tissue distribution of total radioactivity and incorporation of 1-(2
      deoxy-2-fluoro-beta-D-arabinofuranosyl) 5-methyluracil (FMAU), derived from
      thymidylate synthase activation of FAU, into tumor DNA was measured. Positron
      emission tomography (PET) images were obtained for 90 minutes after injection of
      [18F]-FAU. Thymidylate synthase activity was determined in vitro in tumors from
      untreated mice by [3H] release from [3H]dUMP. Each cell line was incubated in
      vitro with [3H]-FAU or [3H]-FMAU in the absence or presence of 5-fluoro-2'
      deoxyuridine (FdUrd) and then was analyzed for incorporation of radiolabel into
      DNA. RESULTS: Thymidylate synthase enzymatic activity in LS174T xenografts was
      approximately 3.5-fold higher than in HT29 xenografts, and incorporation of
      radioactivity derived from [3H]-FAU into LS174T DNA was approximately 2-fold
      higher than into HT29 DNA. At 240 minutes, radioactivity derived from [3H]-FAU
      was approximately 2-fold higher in tumors than in skeletal muscle. At times up to
      90 minutes, PET imaging detected only small differences in uptake of [18F]-FAU
      between the tumor types. Fluorine-18 in skeletal muscle was higher than in tumor
      for the first 90 minutes and plateaued earlier, whereas [18F] in tumor continued
      to increase during the 90-minute imaging period. For both cell lines in vitro,
      FdUrd decreased the rate of incorporation of [3H]-FAU into DNA, whereas the
      incorporation of [3H]-FMAU was increased. CONCLUSIONS: These results for FAU
      incorporation into DNA in vitro and in vivo further support clinical evaluation
      of FAU as a therapeutic agent in tumors with high concentrations of thymidylate
      synthase that are less likely to respond to 5-fluorouracil treatment. The high
      circulating concentrations of thymidine reported in mice may limit their utility
      in evaluating FAU as a PET probe.

PMID- 15475458
TI  - Characterization of the hollow fiber assay for the determination of microtubule
      disruption in vivo.
AB  - PURPOSE: The hollow fiber assay is used successfully as a routine in vivo
      screening model to quantitatively define anticancer activity by the National
      Cancer Institute. This study investigates whether the hollow fiber assay can be
      used as a short-term in vivo model to demonstrate specific pharmacodynamic end
      points, namely microtubule and cell cycle disruption. EXPERIMENTAL DESIGN: The
      growth of A549 cells was characterized within hollow fibers over 5 days in vivo
      at both subcutaneous (s.c.) and intraperitoneal (i.p.) sites. Drugs were
      administered on day 4 (i.p.). RESULTS: At 24 hours, cells were retrieved from
      fibers at both i.p. and s.c. sites of paclitaxel-treated (20 mg/kg) and
      combretastatin A1 phosphate-treated (150 mg/kg) mice. Cell cycle analysis after
      paclitaxel treatment revealed a mean G(2)-M phase population of 48.04% (i.p.) and
      25.76% (s.c.) compared with vehicle group mice (6.78 and 5.56%, respectively; P =
      <0.001 and 0.005, respectively). Tumor cells retrieved from combretastatin A1
      phosphate-treated mice had a mean G2-M phase population of 36.3% (i.p.) and
      29.36% (s.c.) compared with cells retrieved from vehicle group mice (5.58 and
      5.49%, respectively; P = <0.001). Using fluorescence and laser-confocal
      microscopy, paclitaxel was revealed to induce the formation of spindle asters and
      tubulin polymerization. Combretastatin A1 phosphate was shown to hold cells in
      mitosis. Changes in nuclear morphology were also observed. CONCLUSION: These data
      demonstrate that the hollow fiber assay can be used as a short-term in vivo model
      for studying the pharmacodynamic effects of both standard and novel compounds on
      microtubules. Evidence has also been provided to support the routine use of the
      in vivo hollow fiber assay for demonstrating the mechanism of action of a drug.

PMID- 15475459
TI  - A selective c-met inhibitor blocks an autocrine hepatocyte growth factor growth
      loop in ANBL-6 cells and prevents migration and adhesion of myeloma cells.
AB  - PURPOSE: We wanted to examine the role of the hepatocyte growth factor (HGF)
      receptor c-Met in multiple myeloma by applying a novel selective small molecule
      tyrosine kinase inhibitor, PHA-665752, directed against the receptor.
      EXPERIMENTAL DESIGN: Four biological sequels of HGF related to multiple myeloma
      were studied: (1) proliferation of myeloma cells, (2) secretion of interleukin-11
      from osteogenic cells, (3) migration of myeloma cells, and (4) adhesion of
      myeloma cells to fibronectin. We also examined effects of the c-Met inhibitor on
      intracellular signaling pathways in myeloma cells. RESULTS: PHA-665752
      effectively blocked the biological responses to HGF in all assays, with 50%
      inhibition at 5 to 15 nmol/L concentration and complete inhibition at around 100
      nmol/L. PHA-665752 inhibited phosphorylation of several tyrosine residues in c
      Met (Tyr(1003), Tyr(1230/1234/1235), and Tyr(1349)), blocked HGF-mediated
      activation of Akt and p44/42 mitogen-activated protein kinase, and prevented the
      adaptor molecule Gab1 from complexing with c-Met. In the HGF-producing myeloma
      cell line ANBL-6, PHA-665752 revealed an autocrine HGF-c-Met-mediated growth
      loop. The inhibitor also blocked proliferation of purified primary myeloma cells,
      suggesting that autocrine HGF-c-Met-driven growth loops are important for
      progression of multiple myeloma. CONCLUSIONS: Collectively, these findings
      support the role of c-Met and HGF in the proliferation, migration, and adhesion
      of myeloma cells and identify c-Met kinase as a therapeutic target for treatment
      of patients with multiple myeloma.

PMID- 15475460
TI  - Ran, a small GTPase gene, encodes cytotoxic T lymphocyte (CTL) epitopes capable
      of inducing HLA-A33-restricted and tumor-reactive CTLs in cancer patients.
AB  - PURPOSE: The purpose is to identify a gene coding for tumor-associated antigen
      and peptide capable of inducing CTLs reactive to tumor cells with a HLA-A33
      restricted fashion to provide scientific basis for specific immunotherapy to HLA
      A33+ cancer patients. EXPERIMENTAL DESIGN: An expression gene-cloning method was
      used to identify the tumor-associated antigen gene. Northern blot analysis and
      immunohistochemistry were used to examine the mRNA and protein expression levels
      in various cells and tissues, respectively. Synthetic peptides were examined for
      their ability to induce HLA-A33+ tumor-reactive CTLs in peripheral blood
      mononuclear cells from cancer patients. RESULT: A gene of small GTPase, Ran,
      which controls the cell cycle through the regulation of nucleocytoplasmic
      transport, mitotic spindle organization, and nuclear envelope formation, was
      found to encode epitopes recognized by the HLA-A33-restricted CTLs established
      from T cells infiltrating into gastric adenocarcinoma. The expression of the Ran
      gene was increased in most cancer cell lines and cancer tissues at both the mRNA
      and protein levels. However, it was not enhanced in the surrounding normal cells
      or tissues. It was also undetectable in normal tissues as far as tested. Ran
      derived peptides at positions 48-56 and 87-95 could induce CD8+ peptide-specific
      CTLs reactive to tumor cells from HLA-A33+ epithelial cancer patients in a HLA
      class I-restricted manner. CONCLUSIONS: Because of its increased expression in
      cancer cells and involvement in malignant transformation and/or the enhanced
      proliferation of cancer cells, the two Ran-directed peptides could be potent
      candidates in use for specific immunotherapy against HLA-A33+ epithelial cancers.

PMID- 15475461
TI  - Overexpression of 5-lipoxygenase in rat and human esophageal adenocarcinoma and
      inhibitory effects of zileuton and celecoxib on carcinogenesis.
AB  - PURPOSE: Aberrant arachidonic acid (AA) metabolism, especially through the
      cyclooxygenase (Cox) and 5-lipoxygenase (5-Lox) pathways, has been suggested to
      play an important role in the development of esophageal adenocarcinoma (EAC). The
      purpose of this study was to investigate the expression of 5-Lox in EAC of a rat
      model and in human samples as well as the chemopreventive effects of zileuton (a
      specific 5-Lox inhibitor) and celecoxib (a specific Cox2 inhibitor) in the rat
      EAC model. EXPERIMENTAL DESIGN: 5-Lox expression in EAC of a rat
      esophagogastroduodenal anastomosis model and of humans was examined with
      immunohistochemistry. A chemoprevention study was designed to test whether
      zileuton and celecoxib could suppress aberrant AA metabolism and esophageal
      adenocarcinogenesis. RESULTS: With immunohistochemistry, we found that 5-Lox was
      overexpressed during esophageal adenocarcinogenesis in our rat model and in
      humans. In the chemoprevention study, EAC incidence was reduced in a dose
      dependent manner from 68.8% (11 of 16) to 44.4% (8 of 18; P > 0.05) and 31.3% (5
      of 16; P < 0.05) by 500 and 1,000 ppm zileuton, respectively, and to 33.3% (7 of
      21; P < 0.05) and 20% (3 of 15; P < 0.05) by 500 and 1,000 ppm celecoxib,
      respectively. With isobolographic analysis, zileuton and celecoxib, both at a
      dose of 500 ppm, had an additive effect by reducing the tumor incidence to 16.7%
      (3 of 18, P < 0.01). Leukotriene B4 and prostaglandin E2 levels in the esophageal
      tissues were also significantly reduced by zileuton and celecoxib. CONCLUSIONS:
      This study clearly demonstrated that 5-Lox and Cox2 play important roles in the
      development of EAC. Both zileuton and celecoxib had inhibitory effects on
      esophageal adenocarcinogenesis through inhibition on their respective enzymes of
      AA metabolism.

PMID- 15475462
TI  - Synergistic effects of acyclic retinoid and OSI-461 on growth inhibition and gene
      expression in human hepatoma cells.
AB  - Hepatoma is one of the most frequently occurring cancers worldwide. However,
      effective chemotherapeutic agents for this disease have not been developed.
      Acyclic retinoid, a novel synthetic retinoid, can reduce the incidence of
      postsurgical recurrence of hepatoma and improve the survival rate. OSI-461, a
      potent derivative of exisulind, can increase intracellular levels of cyclic GMP,
      which leads to activation of protein kinase G and induction of apoptosis in
      cancer cells. In the present study, we examined the combined effects of acyclic
      retinoid plus OSI-461 in the HepG2 human hepatoma cell line. We found that the
      combination of as little as 1.0 micromol/L acyclic retinoid and 0.01 micromol/L
      OSI-461 exerted synergistic inhibition of the growth of HepG2 cells. Combined
      treatment with low concentrations of these two agents also acted synergistically
      to induce apoptosis in HepG2 cells through induction of Bax and Apaf-1, reduction
      of Bcl-2 and Bcl-xL, and activation of caspase-3, -8, and -9. OSI-461 enhanced
      the G0-G1 arrest caused by acyclic retinoid, and the combination of these agents
      caused a synergistic decrease in the levels of expression of cyclin D1 protein
      and mRNA, inhibited cyclin D1 promoter activity, decreased the level of
      hyperphosphorylated forms of the Rb protein, induced increased cellular levels of
      the p21(CIP1) protein and mRNA, and stimulated p21(CIP1) promoter activity.
      Moreover, OSI-461 enhanced the ability of acyclic retinoid to induce increased
      cellular levels of retinoic acid receptor beta and to stimulate retinoic acid
      response element-chloramphenicol acetyltransferase activity. A hypothetical model
      involving concerted effects on p21(CIP1) and retinoic acid receptor beta
      expression is proposed to explain these synergistic effects. Our results suggest
      that the combination of acyclic retinoid plus OSI-461 might be an effective
      regimen for the chemoprevention and chemotherapy of human hepatoma and possibly
      other malignancies.

PMID- 15475463
TI  - A predictive model of human myelotoxicity using five camptothecin derivatives and
      the in vitro colony-forming unit granulocyte/macrophage assay.
AB  - PURPOSE: Many promising anticancer drugs are limited by myelosuppression. It is
      difficult to evaluate human myelotoxicity before a Phase I study because of the
      susceptibility of humans and animals to hematotoxicity. The purpose of this study
      was to establish a reliable method to predict the human maximum tolerated dose
      (MTD) of five camptothecin derivatives: SN-38, DX-8951f, topotecan, 9
      aminocamptothecin, and camptothecin. EXPERIMENTAL DESIGN: The myelotoxicity of SN
      38 and DX-8951f were evaluated on bone marrow from mice, dogs, and humans using a
      14-day colony-forming unit, granulocyte-macrophage (CFU-GM) assay to determine
      the 50%, 75%, and 90% inhibitory concentration values (IC50, IC75, and IC90,
      respectively). RESULTS: Species differences in myelotoxicity were observed for SN
      38 and DX-8951f. Using human and murine IC90s for myelotoxicity of these
      compounds and other camptothecin compounds (topotecan, 9-aminocamptothecin, and
      camptothecin), in vivo toxicological data, and pharmacokinetic parameters (data
      referred to in the literature), human MTDs were predicted retrospectively. The
      mechanism-based prediction model that is proposed uses the in vitro camptothecin
      assay and in vivo parameters on the basis of free fraction of area under the
      concentration-curve at the MTD (r2 = 0.887) and suggests that the human MTDs were
      well predicted for the five camptothecin derivatives by this model rather than by
      other models. CONCLUSION: The human MTDs of the camptothecin drugs were
      successfully predicted using the mechanism-based prediction model. The
      application of this model for in vitro hematotoxicology could play an important
      role for the development of new anticancer agents.

PMID- 15475464
TI  - Inhibition of the type III epidermal growth factor receptor variant mutant
      receptor by dominant-negative EGFR-CD533 enhances malignant glioma cell
      radiosensitivity.
AB  - PURPOSE: The commonly expressed variant epidermal growth factor receptor (EGFR),
      the type III EGFR variant (EGFRvIII), functions as an oncoprotein promoting
      neoplastic transformation and tumorigenicity. The role of EGFRvIII in cellular
      responses to genotoxic stress, such as ionizing radiation, is only minimally
      defined. Thus, we have investigated EGFRvIII as a potential modulator of cellular
      radiation responses and explored the feasibility of adenovirus (Ad)-mediated
      expression of dominant-negative EGFR-CD533 as a gene therapeutic approach for
      inhibiting EGFRvIII function in vitro and in vivo. EXPERIMENTAL DESIGN AND
      RESULTS: EGFR-CD533 and EGFRvIII were expressed in vitro and in vivo in malignant
      U-373 MG glioma cells through transduction with an Ad vector, Ad-EGFR-CD533 and
      Ad-EGFRvIII, respectively. In vivo studies defined the importance of EGFRvIII as
      a modulator of radiation responses, demonstrating a 2.6-fold activation of
      EGFRvIII in U-373 malignant glioma tumors. Concomitant expression of EGFR-CD533
      inhibited the radiation-induced activation of EGFRvIII in vitro and completely
      abolished the enhanced clonogenic survival conferred by EGFRvIII. The ability of
      EGFR-CD533 to inhibit EGFRvIII function was further confirmed in vivo through
      complete inhibition of EGFRvIII-mediated increased tumorigenicity and radiation
      induced activation of EGFRvIII. Growth delay assays with U-373 xenograft tumors
      demonstrated that the expression of EGFR-CD533 significantly enhanced
      radiosensitivity of tumor cells under conditions of intrinsic and Ad-mediated
      EGFRvIII expression. CONCLUSIONS: We conclude that EGFRvIII confers significant
      radioresistance to tumor cells through enhanced cytoprotective responses, and we
      have demonstrated that dominant-negative EGFR-CD533 effectively inhibits EGFRvIII
      function. These data affirm the broad potential of EGFR-CD533 to radiosensitize
      human malignant glioma cells.

PMID- 15475465
TI  - Cisplatin rapidly down-regulates its own influx transporter hCTR1 in cultured
      human ovarian carcinoma cells.
AB  - PURPOSE: Cisplatin (DDP)-resistant cells commonly exhibit reduced drug
      accumulation. Previous studies have shown that the major copper (Cu) influx
      transporter CTR1 controls the uptake of DDP in yeast and mammalian cells. The
      goal of this study was to examine the effect of Cu and DDP on the level and
      subcellular localization of hCTR1 protein in human ovarian carcinoma cells.
      EXPERIMENTAL DESIGN: Cultured human ovarian carcinoma A2780 cells were exposed to
      DDP and Cu, and the effect on hCTR1 was determined using Western blot analysis
      and confocal digital deconvolution microscopy. RESULTS: Loss of hCTR1 was
      triggered by DDP exposure in a concentration and time-dependent manner. Exposure
      to 0.5 micromol/L DDP for 5 minutes reduced hCTR1 levels and exposure to DDP
      concentrations > or =2 micromol/L caused almost complete disappearance. The loss
      of hCTR1 was observed within 1 minute of the start of exposure to 2 micromol/L
      DDP. Treatment of cells with 100 micromol/L Cu for 5 minutes produced a smaller
      effect. Pretreatment of cells with 2 micromol/L DDP for 5 minutes resulted in a
      50% decrease in 64Cu uptake, demonstrating that the DDP-induced loss of hCTR1
      detected by Western blot analysis and imaging was functionally significant.
      CONCLUSIONS: DDP down-regulated the amount of its major influx transporter in
      cultured human ovarian carcinoma cells in a concentration- and time-dependent
      manner. The effect was observed at DDP concentrations within the range found in
      the plasma of patients being treated with DDP, and it occurred very quickly
      relative to the half-life of the drug.

PMID- 15475466
TI  - Sp1-mediated transcriptional control of fibroblast growth factor receptor 4 in
      sarcomas of skeletal muscle lineage.
AB  - Fibroblast growth factor receptors (FGFRs) have been implicated in a multitude of
      differentiating and proliferative actions. FGFR4 is expressed mainly in lung,
      kidney, pancreas, spleen, and developing muscle. FGFR4 was found to be
      overexpressed in some human malignancies, where it has been implicated in their
      pathogenesis. Recently, FGFR4 was found to be overexpressed in pediatric
      rhabdomyosarcomas, based on cDNA microarray analysis. Using Northern blotting,
      reverse transcription-polymerase chain reaction, and Western blotting, we
      classified four human rhabdomyosarcoma-derived cell lines based on their relative
      expression of FGFR4. We defined a 214 bp (-115/+99) promoter that functioned as a
      minimal promoter and examined cis-DNA elements implicated in the control of
      expression of the FGFR4 gene in these cells. Overlapping 40- to 50-bp fragments
      of the minimal promoter were examined by electrophoretic mobility shift assay
      using nuclear extracts from cell lines with high (HS729-1015) or low (HS729-1016)
      FGFR4 expression. Fragment C (-65/-26) formed specific complexes with nuclear
      extracts from both cell lines. Fragment B (-95/-56), however, formed distinct
      complexes mainly with the high FGFR4-expressing HS729-1015 cells. Both fragments
      yielded complexes that were competed by an Sp oligonucleotide and supershifted by
      Sp1 and by Sp3 antibodies. Transfection of Sp1 but not Sp3 efficiently activated
      FGFR4 promoter activity, an effect that was significantly more pronounced in the
      HS729-1015 cell line than in the low FGFR4-expressing HS729-1016 cell line.
      Deletion of each of the two Sp-binding sites in fragments B and C resulted in
      loss of promoter activity. In particular, deletion of the 5' Sp-binding site in
      fragment B was associated with the greatest loss of activity. Sp1 protein
      expression correlated with FGFR4 expression in cell lines and primary human
      rhabdomyosarcomas. Furthermore, transfection of Sp1 and methylation inhibition
      was effective in inducing the endogenous FGFR4 gene in HS729-1015 cells. Our
      findings point to Sp1 as an important contributor to FGFR4 transcriptional
      control and elucidate a potential mechanism for the heterogeneous expression of
      FGFR4 in neoplasms derived from the same cell lineage.

PMID- 15475468
TI  - Comparing two methods to obtain blood specimens from pediatric central venous
      catheters.
AB  - The purpose of this study was to test agreement in blood values obtained from a
      discard method and a push-pull method in samples from central venous catheters in
      pediatric patients. The discard method causes blood loss beyond what is necessary
      for blood testing and increases potential for infection each time the central
      venous catheter is entered. Twenty-eight children ranging in age from 6 months to
      12 years were enrolled in the study. A research protocol was developed to pair
      the 2 methods of blood collection for each sample. The Bland-Altman method was
      used to test agreement on each blood value for each paired sample. Of the 438
      pairs of measured blood values, 420 (95.9%) fell within the limits of agreement.
      Nurses reported no difficulty in using the push-pull technique to obtain any
      samples. The push-pull method of obtaining blood specimens from pediatric central
      venous catheters should be considered. It can eliminate blood loss through
      discard and can reduce infection because it reduces the number of times a
      catheter is entered.

PMID- 15475469
TI  - Information needs of adolescents with cancer.
AB  - Adolescents with cancer (AWC) have poorer treatment outcomes as well as higher
      incidence and mortality rates than do younger children, and they face additional
      challenges related to normal developmental issues of adolescence. Although
      research has shown that information on the cancer experience improves outcomes by
      decreasing uncertainty and increasing perceived support, little is known about
      the types of information AWC need and want. This study describes how AWC rate the
      importance of specific cancer-related information, analyzes gender and age group
      differences, and compares 2 different time-since-diagnosis groups of AWC. The
      sample consisted of adolescents with newly diagnosed cancer (n = 74) and those 1
      to 3 years from diagnosis (n = 39). The Information Preferences of Adolescents
      (IPA) Scale was used to measure the adolescents' information needs. Both samples
      of AWC rated the need for information as high. There were no significant
      differences by age, but females had significantly higher total scores for both
      groups and for many item means in the newly diagnosed group. Qualitative analysis
      of the additional write-in items generated 4 themes: treatment/side effects,
      uncertainty, social issues, and personal/emotional issues.

PMID- 15475470
TI  - Pediatric oncology professionals' perceptions of information needs of adolescent
      patients with cancer.
AB  - In contrast to the extensive research on the information needs of older patients
      with cancer, the question of what information is most relevant for adolescents
      seems to have been addressed in only one published study. The aim of the present
      study was to update and extend the sole previous survey of oncology
      professionals' views about the information needs of adolescent patients. This was
      achieved by including professionals other than physicians, by structuring the
      questionnaire to show whether perceived information needs were different for the
      time of diagnosis versus during treatment, and by differentiating between the 6
      cancer diagnoses most commonly affecting adolescents. Fifteen hundred surveys
      were distributed to pediatric cancer professionals, and 556 valid returns were
      analyzed. The main finding was that information was considered more important to
      provide during treatment than at the time of diagnosis. Also, medical information
      topics were generally considered more essential than psychological topics. The
      magnitude of this difference was influenced to a small extent by professional
      discipline, gender, age and experience of respondent, and whether the information
      was being given at diagnosis or during treatment. It is notable that whereas
      respondents generally were confident in their ability to communicate information,
      physicians rated themselves as better communicators at the time of diagnosis than
      during treatment.

PMID- 15475471
TI  - Nurses' perceptions of phase I clinical trials in pediatric oncology: a review of
      the literature.
AB  - A review of literature was conducted to explore nurses' perceptions of phase I
      clinical trials in pediatric oncology. Specifically, nurses' perceptions of the
      goals and outcomes, the nurse's role, and the informed consent process in
      pediatric oncology phase I clinical trials were investigated. Findings on
      possible factors influencing the nurses' perceptions and the quality of work-life
      of nurses working at pediatric phase I clinical trial centers were also searched.
      However, despite an extensive review of published works, no studies on nurses'
      perceptions of phase I trials in pediatric oncology were found. Therefore, this
      literature review consists of findings in similar or related studies such as
      nurses' perceptions of experimental therapies in the adult setting, adult
      patients' perceptions, parents' perceptions, or oncologists'perceptions of phase
      I clinical trials.

PMID- 15475472
TI  - Neuropathic pain in children with cancer.
AB  - Different mechanisms of cancer pain may involve somatic, visceral, and neural
      tissues. Pain that involves the neural tissues is classified as neuropathic pain
      and is less responsive to analgesics than pain that involves somatic and visceral
      tissues. Because young children are unable to describe the quality of pain,
      presence of neuropathic pain with cancer may be unrecognized and undetected. The
      purpose of this article is to explain the nature of neuropathic pain, to review
      the literature related to children with cancer that suggests the presence of
      neuropathic pain, to outline assessment strategies that may lead to appropriate
      detection of neuropathic pain in children, and to discuss challenges in the
      management of neuropathic pain. Future research is needed to characterize the
      intensity, location, quality, and duration of neuropathic pain in children. In
      addition, research that would determine the efficacy of opioids, nonsteroidal
      anti-inflammatory drugs, and adjuvant analgesics (antidepressants,
      anticonvulsants) is needed to increase the nurses' ability to assess and manage
      neuropathic pain in children with cancer.

PMID- 15475473
TI  - Weight gain and height velocity in young children 1 year following bone marrow
      transplant: a single institution study.
AB  - The nutritional and growth effects on children following a bone marrow transplant
      (BMT) have not been well documented. The purpose of this study was to describe
      the growth patterns of young children during the first year following BMT. A
      retrospective chart review was used to examine the nutritional status of 25 young
      children, 1 to 6 years of age, who received an allogeneic BMT. Nutritional data
      were reviewed prior to BMT and at 3, 6, 9, and 12 months following BMT. The mean
      weight gain was 2.5 kg with a median weight gain of 2.3 kg (range, -1.2 to 9.4
      kg). The mean height gain was 7 cm with a median height gain of 7.4 cm (range,
      1.2 to 16.8 cm). Growth related to gender, age, and incidence of infection was
      similar to the overall average; however, children with graft-versus-host disease
      revealed poor weight and height gain. Nurses must learn to recognize patients at
      nutritional risk and intervene when necessary. More research is needed to address
      specific nutritional needs of the pediatric BMT patient.

PMID- 15475475
TI  - High-content screening with siRNA optimizes a cell biological approach to drug
      discovery: defining the role of P53 activation in the cellular response to
      anticancer drugs.
AB  - Deciphering the effects of compounds on molecular events within living cells is
      becoming an increasingly important component of drug discovery. In a model
      application of the industrial drug discovery process, the authors profiled a
      panel of 22 compounds using hierarchical cluster analysis of multiparameter high
      content screening measurements from nearly 500,000 cells per microplate. RNAi
      protein knockdown methodology was used with high-content screening to dissect the
      effects of 2 anticancer drugs on multiple target activities. Camptothecin
      activated p53 in A549 lung carcinoma cells pretreated with scrambled siRNA,
      exhibited concentration-dependent cell cycle blocks, and induced moderate
      microtubule stabilization. Knockdown of camptothecin-induced p53 protein
      expression with p53 siRNA inhibited the G1/S blocking activity of the drug and
      diminished its microtubule-stabilizing activity. Paclitaxel activated p53 protein
      at low concentrations but exhibited G2/M cell cycle blocking activity at higher
      concentrations where microtubules were stabilized. In cells treated with p53
      siRNA, paclitaxel failed to activate p53 protein, but the knockdown did not have
      a significant effect on the ability of paclitaxel to stabilize microtubules or
      induce a G2/M cell cycle block. Thus, this model application of the use of RNAi
      technology within the context of high-content screening shows the potential to
      provide massive amounts of combinatorial cell biological information on the
      temporal and spatial responses that cells mount to treatment by promising
      therapeutic candidates.

PMID- 15475476
TI  - Development and implementation of a highly miniaturized confocal 2D-FIDA-based
      high-throughput screening assay to search for active site modulators of the human
      heat shock protein 90beta.
AB  - The beta isoform of the heat shock protein 90 (Hsp90beta) is a cellular chaperone
      required for the maturation of key proteins involved in growth response to
      extracellular factors as well as oncogenic transformation of various cell types.
      Compounds that inhibit the function of Hsp90beta are thus believed to have
      potential as novel anticancer drugs. To date, 2 fungal metabolites are known to
      inhibit Hsp90beta. However, insolubility and liver toxicity restrict the clinical
      use of these molecules. The limitation to identify novel and safe Hsp90beta
      inhibitors is that presently no suitable high-throughput screening assay is
      available. Here, the authors present the development of a homogenous assay based
      on 2-dimensional fluorescence intensity distribution analysis of tetramethyl
      rhodamine (TAMRA)-labeled radicicol bound to Hsp90beta. Furthermore, the assay
      has been shown to be compatible with the confocal nanoscreening platform Mark II
      from Evotec-Technologies and can therefore be used for miniaturized high
      throughput screening. The applied detection technology provides critical
      information about the nature of biomolecular interaction at the thermodynamic
      equilibrium, such as affinity constants and stoichiometric parameters of the
      binding. The assay is used to identify small molecular weight compounds
      displacing TAMRA-radicicol. Such compounds are believed to be important molecules
      in the discovery of novel anticancer drugs.

PMID- 15475477
TI  - A generally applicable, high-throughput screening-compatible assay to identify,
      evaluate, and optimize antimicrobial agents for drug therapy.
AB  - Efficacy and tolerability are the key criteria for a successful medication in the
      clinic. Therefore, a new test method to obtain selective and active lead
      molecules has been developed. Recently, this novel screening strategy enabled a
      breakthrough in drug discovery in the field of herpes viruses. Here the authors
      report that this assay is a generally applicable screening test, which allows not
      only for identifying tolerable and potent antimicrobial agents in compound
      libraries, but also covers all potential in vitro targets of both the pathogen
      and the host simultaneously. The test system mimics the smallest unit of a
      natural infection. Host cells are incubated in the presence of the test sample
      and are infected with microbes, such as viruses, bacteria, or fungi. Analogous to
      (lethal challenge) animal models, cell survival is determined. This assay
      maximizes the chances of success of anti-infective drug discovery, is sensitive,
      robust, time- and cost-efficient, and especially effective in optimizing
      screening hits to lead structures and development candidates. In addition to the
      minimal inhibitory concentration or dose, this test system simultaneously
      provides the selectivity index, a measure of tolerability in vitro. The authors
      propose the activity selectivity assay format as a new standard in anti-infective
      drug discovery and clinical development.

PMID- 15475478
TI  - Rb+ flux through hERG channels affects the potency of channel blocking drugs:
      correlation with data obtained using a high-throughput Rb+ efflux assay.
AB  - The nonradioactive Rb+ efflux assay has become a reliable and efficient high
      throughput hERG screening method, but it is limited by its low sensitivity for
      potent hERG blockers. Using the patch clamp technique, the authors found that the
      low sensitivity is due in part to the use of Rb+ as the permeating cation in the
      assay. The affinities of the drugs measured by patch clamp technique in the
      presence of Rb+ were 3- to 10-fold lower than when measured by the same method in
      the presence of K+ ions. The apparent affinity of the drugs decreased even
      further when monitored by the Rb+ efflux assay. It was also observed that Rb+ had
      minimal effects on the activation properties of channels while there was a
      significant change in the half-inactivation potential. This voltage shift reduces
      hERG channel inactivation at efflux assay potentials, and will reduce the
      affinity of hERG-blocking drugs that bind to inactivated states of the channel.
      In combination with the effects of elevated extracellular ion concentrations, it
      is likely that Rb+ modulation of hERG channel inactivation is largely responsible
      for the reduced drug potencies observed in the Rb+ efflux assay.

PMID- 15475479
TI  - Comparison of in vitro models for the prediction of compound absorption across
      the human intestinal mucosa.
AB  - Several in vitro assays have been developed to evaluate the gastrointestinal
      absorption of compounds. Our aim was to compare 3 of these methods: 1) the bio
      mimetic artificial membrane permeability assay (BAMPA) method, which offers a
      high-throughput, noncellular approach to the measurement of passive transport; 2)
      the traditional Caco-2 cell assay, the use of which as a high-throughput tool is
      limited by the long cell differentiation time (21 days); and 3) The BioCoat high
      throughput screening Caco-2 Assay System, which reduces Caco-2 cell
      differentiation to 3 days. The transport of known compounds (such as cephalexin,
      propranolol, or chlorothiazide) was studied at pH 7.4 and 6.5 in BAMPA and both
      Caco-2 cell models. Permeability data obtained was correlated to known values of
      human absorption. Best correlations (r = 0.9) were obtained at pH 6.5 for BAMPA
      and at pH 7.4 for the Caco-2 cells grown for 21 days. The Caco-2 BioCoat HTS Caco
      2 Assay System does not seem to be adequate for the prediction of absorption. The
      overall results indicate that BAMPA and the 21-day Caco-2 system can be
      complementary for an accurate prediction of human intestinal absorption.

PMID- 15475480
TI  - Development of a colorimetric method for functional chloride channel assay.
AB  - Anion channels play significant physiological roles in humans and animals.
      However, the effort of screening for anion channel modulators was limited by the
      available assay technologies. This report discusses the development of a cell
      based functional chloride channel assay using iodine as the chloride channel
      functional indicator. Iodine concentrations were measured with modified Sandell
      Kolthoff reaction using colorimetric detection. The assay was rapid and
      quantitative. When WSS-1 cells were activated by gamma-aminobutyric acid (GABA)
      in the condition that gamma-aminobutyric acid type A receptor (GABAA receptor)
      conducted outwardly rectifying chloride channel function, the EC50 of GABA was
      7.69 microM. IC50s were 0.53 microM for bicuculline and 3.1 microM for
      picrotoxin, respectively, in the presence of 10 microM GABA. When Capan-1 cells
      were activated by forskolin, the EC50 was 0.14 microM. The assay can also be
      applied to inwardly rectifying anion channels as exemplified by GABAA channel
      with an EC50 of 294 microM. Thus, the assay is universal and reliable and can be
      used for anion channel high-throughput screening.

PMID- 15475481
TI  - A high-throughput turbidometric assay for screening inhibitors of protein
      disulfide isomerase activity.
AB  - Protein disulfide isomerase (PDI) plays a key role in protein folding by
      catalyzing rearrangements of disulfide bonds in substrate proteins following
      their synthesis in eukaryotic cells. Besides its major role in the processing and
      maturation of secretory proteins in the endoplasmic reticulum, this enzyme and
      its homologs have been implicated in multiple important cellular processes;
      however, they have not served as targets for the development of therapeutic
      agents. The authors developed a high-throughput screening assay for PDI and its
      homologous enzymes in 384-well microplates. The method is based on the enzyme
      catalyzed reduction of insulin in the presence of dithiothreitol and measures the
      aggregation of reduced insulin chains at 650 nm. This kinetic assay was converted
      to an end-point assay by using hydrogen peroxide as a stop reagent. The
      feasibility of this high-throughput assay for screening chemical libraries was
      demonstrated in a pilot screen. The authors show that this homogenous
      turbidometric assay is robust and cost-effective and can be applied to identify
      PDI inhibitors from chemical libraries, opening this class of enzymes for
      therapeutic exploration.

PMID- 15475482
TI  - Conformation-sensitive gel electrophoresis as an ideal high-throughput strategy
      for accurate detection of sequence variations in DNA: screening hTomm and hTimm
      genes.
AB  - Conformation-sensitive gel electrophoresis is a heteroduplex-based method that is
      particularly well suited to high-throughput analyses. Its simplicity makes it
      amenable to various adaptations and modifications to enhance its applicability to
      genome-wide mutation scans. Technical aspects that markedly improve the
      conformation-sensitive gel electrophoresis performance by combining high
      throughput and high resolution of the bands facilitating the interpretation of
      the results are described here. The authors report some of the results they have
      obtained in the screening of the exon 1 of human Timm8A gene as an example of the
      suitability of the conformation-sensitive gel electrophoresis-based protocol that
      has been adapted to optimize its throughput, speed, and simplicity in the
      recognition of both heterozygous and homozygous DNA mutations. The higher
      throughput is achieved by using 12 batches per gel. The length of the gel is
      sufficient for an adequate well-to-read distance for each batch that allows a
      clear distinction and resolution of the conformation-sensitive gel
      electrophoresis bands. Standardization of the procedure using multichannel
      pipettes reduces the preparation time of the 96-well PCRs to 10 min and also
      accelerates the gel loading. The resulting bands give high-quality images,
      allowing easy detection of known as well as novel mutations.

PMID- 15475483
TI  - Analysis of genetic variations of lamin A/C gene (LMNA) by denaturing high
      performance liquid chromatography.
AB  - The human LMNA gene, when mutated, has been shown to cause at least 7 human
      diseases: dilated cardiomyopathy, Emery Dreifuss muscular dystrophy, limb girdle
      muscular dystrophy, familial partial lipodystrophy, Charcot Marie tooth disease
      type II, mandibuloacral dysplasia, and Hutchinson-Gilford Progeria (OMIM
      #176670). This article describes a high-throughput method for screening the human
      lamin A/C (LMNA) gene for genetic mutations and sequence variation using
      denaturing high-performance liquid chromatography (DHPLC). In the present study,
      76 patients with dilated cardiomyopathy were screened for mutations using DHPLC
      and sequence analysis. Abnormal elution profiles were identified and sequenced on
      an ABI 377 automatic sequencer. Heterozygous LMNA mutations were detected in 8%
      of the affected patients. In addition, a number of intronic and exonic single
      nucleotide polymorphisms were identified. LMNA mutations are clinically relevant
      in at least 6 human diseases. This study provides a protocol for high-throughput
      LMNA analysis applicable both in the research and in the clinical diagnostic
      setting.

PMID- 15475485
TI  - Leptin deficiency enhances sensitivity of rats to alcoholic steatohepatitis
      through suppression of metallothionein.
AB  - Oxidative stress is stated to be a central mechanism of hepatocellular injury in
      alcohol-induced liver injury. Recent reports have shown that Kupffer cell
      dysfunction in the leptin-deficient state contributes partly to the increased
      sensitivity to endotoxin liver injury. Here we report that leptin also plays a
      key role in the development of alcoholic liver injury and that leptin signaling
      in hepatocytes is involved in cellular mechanisms that mediate ethanol-induced
      oxidative stress. We found that chronic ethanol feeding in leptin receptor
      deficient Zucker (fa/fa) rats for 6 wk resulted in a much more severe liver
      injury and augmented accumulation of hepatic lipid peroxidation compared with
      control littermates. The hepatic induction of stress-response and antioxidant
      proteins, such as metallothionein (MT)-1 and -2, was significantly suppressed in
      fa/fa rats after chronic ethanol feeding. Zinc concentration in liver was also
      decreased in fa/fa rats, compared with control littermates. In primary cultured
      hepatocytes from fa/fa rats, incubation with ethanol significantly suppressed MT
      1 and -2 expressions. Addition of leptin to leptin-deficient ob/ob mouse primary
      hepatocytes led to an increase in MT-1 and -2 mRNA levels and a decrease in
      oxidative stress after incubation with ethanol. In conclusion, leptin deficiency
      enhances sensitivity of rats to alcohol-induced steatohepatitis through
      hepatocyte-specific interaction of MT-1 and -2 and resultant exaggeration of
      oxidative stress in hepatocytes. These findings suggest that leptin resistance in
      hepatocytes is an important mechanism of alcohol-induced liver injury.

PMID- 15475487
TI  - The basis for transport across epithelial cells.

PMID- 15475488
TI  - Influence of sildenafil on gastric sensorimotor function in humans.
AB  - After a meal, the proximal stomach relaxes probably through the activation of
      nitrergic neurons in the gastric wall. Nitric oxide-induced smooth muscle
      relaxation involves activation of soluble guanylate cyclase, with cGMP
      production, which is then degradated by phosphodiesterase-5 (PDE-5). The aim of
      this study was to investigate the effect of sildenafil, a selective PDE-5
      inhibitor, on fasting and postprandial proximal gastric volume and on gastric
      emptying rates in humans. A gastric barostat was used to study gastric compliance
      and perception to isobaric distension in healthy subjects before and after
      placebo (n = 13) or sildenafil, 50 mg (n = 15). In 10 healthy subjects, two
      gastric barostat studies were performed in randomized order to study the effect
      of placebo or sildenafil on postprandial gastric relaxation. Similarly, solid and
      liquid gastric emptying rates were studied in 12 healthy subjects. Sildenafil
      significantly increased fasting intragastric volume (141 +/- 15 vs. 163 +/- 15
      ml, P < 0.05) and volumes of first perception. Sildenafil induced a higher and
      prolonged gastric relaxation either at 30 min (357 +/- 38 vs. 253 +/- 42 ml, P <
      0.05) or 60 min (348 +/- 49 vs. 247 +/- 38 ml, P < 0.05) after the meal.
      Sildenafil did not alter solid half-emptying time but significantly delayed
      liquid emptying (43 +/- 4 vs. 56 +/- 4 min, P < 0.01). In conclusion, sildenafil
      significantly increases postprandial gastric volume and slows liquid emptying
      rate, confirming that meal-induced accommodation in humans involves the
      activation of a nitrergic pathway. The effect of sildenafil on gastric fundus
      suggests a therapeutic potential for phosphodiesterase inhibitors in patients
      with impaired gastric accommodation.

PMID- 15475489
TI  - Mechanisms of serum potentiation of GM-CSF production by human airway smooth
      muscle cells.
AB  - Inflammation and vascular leakage are prevalent in asthma. This study aimed to
      elucidate the mechanisms involved in serum potentiation of cytokine-induced
      granulocyte macrophage colony stimulating factor (GM-CSF) production by human
      airway smooth muscle cells and to identify possible factors responsible. Serum
      deprived cells at low density were stimulated with TNF-alpha and IL-1beta for 24
      h. Human AB serum (10%), inhibitors of RNA and protein synthesis or specific
      signaling molecules, or known smooth muscle mitogens were then added for 24 h.
      Culture supernatants were analyzed for GM-CSF levels, and cells were harvested to
      assess viability, cell cycle progression, GM-CSF-specific mRNA content, and p38
      phosphorylation. Serum potentiated GM-CSF release when added before, together
      with (maximal), or after the cytokines. The potentiation involved both new GM-CSF
      specific mRNA production and protein synthesis. The mitogens IGF, PDGF, and
      thrombin all potentiated GM-CSF release, and neutralizing antibodies for EGF,
      IGF, and PDGF reduced the serum potentiation. Inhibitor studies ruled as unlikely
      the involvement of p70(S6kinase) and the MAPK p42/p44, two signaling pathways
      implicated in proliferation, and the involvement of the MAPK JNK, while
      establishing roles for p38 MAPK and NF-kappaB in the potentiation of GM-CSF
      release. Detection of significant p38 phosphorylation in response to serum
      stimulation, through Western blotting, further demonstrated the involvement of
      p38. These studies have provided evidence to support p38 being targeted to
      interrupt the cycle of inflammation, vascular leakage and cytokine production in
      asthma.

PMID- 15475491
TI  - Acute hypoxia and pulmonary vasoconstriction in humans: uncovering the mechanism
      of the pressor response.

PMID- 15475492
TI  - Functional and morphological studies of protein transcytosis in continuous
      endothelia.
AB  - Continuous microvascular endothelium constitutively transfers protein from vessel
      lumen to interstitial space. Compelling recent biochemical, ultrastructural, and
      physiological evidence reviewed herein demonstrates that protein transport is not
      the result of barrier "leakiness" but, rather, is an active process occurring
      primarily in a transendothelial vesicular pathway. Protein accesses the vesicular
      pathway by means of caveolae open to the vessel lumen. Vascular tracer proteins
      appear in free cytoplasmic vesicles within minutes; contents of transport
      vesicles are rapidly deposited into the subendothelial matrix by exocytosis.
      Caveolin-1 deficiency eliminates caveolae and abolishes vesicular protein
      transport; interestingly, exchange vessels develop a compensatory transport mode
      through the opening of a paracellular permeability pathway. The evidence supports
      the transcytosis hypothesis and the concept that transcytosis is a fundamental
      component of transendothelial permeability of macromolecules.

PMID- 15475494
TI  - Lipopolysaccharide increases alveolar type II cell number in fetal mouse lungs
      through Toll-like receptor 4 and NF-kappaB.
AB  - Chorioamnionitis is a major cause of preterm delivery. Infants exposed to
      inflammation in utero and then born preterm may have improved lung function in
      the immediate postnatal period. We developed a mouse model of chorioamnionitis to
      study the inflammatory signaling mechanisms that might influence fetal lung
      maturation. With this in vivo model, we found that Escherichia coli
      lipopolysaccharide (LPS) increased the number of alveolar type II cells in the
      fetal mouse lung. LPS also increased type II cell number in cultured fetal lung
      explants, suggesting that LPS could directly signal the fetal lung in the absence
      of maternal influences. Using immunostaining, we localized cells within the fetal
      mouse lung expressing the LPS receptor molecule Toll-like receptor 4 (TLR4).
      Similar to the signaling pathways in inflammatory cells, LPS activated NF-kappaB
      in fetal lung explants. Activation of the TLR4/NF-kappaB pathway appeared to be
      required, as LPS did not increase the number of type II cells in C.C3H-Tlr4(Lps
      d) mice, a congenic strain containing a loss of function mutation in tlr4. In
      addition, the sesquiterpene lactone parthenolide inhibited NF-kappaB activation
      following LPS exposure and blocked the LPS-induced increase in type II cells. On
      the basis of these data from our mouse model of chorioamnionitis, it appears that
      LPS specifically activated the TLR4/NF-kappaB pathway, leading to increased type
      II cell maturation. These data implicate an important signaling mechanism in
      chorioamnionitis and suggest the TLR4/NF-kappaB pathway can influence lung
      development.

PMID- 15475493
TI  - p38 MAP kinase-dependent regulation of endothelial cell permeability.
AB  - We have previously shown that thrombin induces endothelial cell barrier
      dysfunction via cytoskeleton activation and contraction and have determined the
      important role of endothelial cell myosin light chain kinase (MLCK) in this
      process. In the present study we explored p38 MAP kinase as a potentially
      important enzyme in thrombin-mediated endothelial cell contractile response and
      permeability. Thrombin induces significant p38 MAP kinase activation in a time
      dependent manner with maximal effect at 30 min, which correlates with increased
      phosphorylation of actin- and myosin-binding protein, caldesmon. Both SB-203580
      and dominant negative p38 adenoviral vector significantly attenuated thrombin
      induced declines in transendothelial electrical resistance. Consistent with these
      data SB-203580 decreased actin stress fiber formation produced by thrombin in
      endothelium. In addition, dominant negative p38 had no effect on thrombin-induced
      myosin light chain diphosphorylation. Thrombin-induced total and site-specific
      caldesmon phosphorylation (Ser789) as well as dissociation of caldesmon-myosin
      complex were attenuated by SB-203580 pretreatment. These results suggest the
      involvement of p38 MAP kinase activities and caldesmon phosphorylation in the
      MLCK-independent regulation of thrombin-induced endothelial cell permeability.

PMID- 15475496
TI  - Discovering the role of the adrenal gland in the control of body function.
AB  - This essay looks at the historical significance of three APS classic papers that
      are freely available online: Cannon WB and de la Paz D. Emotional stimulation of
      adrenal secretion. Am J Physiol 28: 64-70, 1911
      (http://ajplegacy.physiology.org/cgi/reprint/28/1/64). Cannon WB. The emergency
      function of the adrenal medulla in pain and the major emotions. Am J Physiol 33:
      356-372, 1914 (http://ajplegacy.physiology.org/cgi/reprint/33/2/356). Cannon WB.
      Studies on the conditions of activity in endocrine glands. V. The isolated heart
      as an indicator of adrenal secretion induced by pain, asphyxia and excitement. Am
      J Physiol 50: 399-432, 1919
      (http://ajplegacy.physiology.org/cgi/reprint/50/3/399).

PMID- 15475497
TI  - The pioneering use of systems analysis to study cardiac output regulation.
AB  - This essay examines the historical significance of an APS classic paper that is
      freely available online: Guyton AC, Lindsey AW, and Kaufmann BN. Effect of mean
      circulatory filling pressure and other peripheral circulatory factors on cardiac
      output. Am J Physiol 180: 463-468, 1955
      (http://ajplegacy.physiology.org/cgi/reprint/180/3/463).

PMID- 15475498
TI  - Hypothalamic control of body temperature: insights from the past.
AB  - This essay looks at the historical significance of three APS classic papers that
      are freely available online: Hammel HT, Hardy JD, and Fusco MM. Thermoregulatory
      responses to hypothalamic cooling in unanesthetized dogs. Am J Physiol 198: 481
      486, 1960 (http://ajplegacy.physiology.org/cgi/reprint/198/3/481). Hammel HT,
      Jackson DC, Stolwijk JAJ, Hardy JD, and Stromme SB. Temperature regulation by
      hypothalamic proportional control with an adjustable set point. J Appl Physiol
      18: 1146-1154, 1963 (http://jap.physiology.org/cgi/reprint/18/6/1146). Hellstrom
      B and Hammel HT. Some characteristics of temperature regulation in the
      unanesthetized dog. Am J Physiol 213: 547-556, 1967
      (http://ajplegacy.physiology.org/cgi/reprint/213/2/547).

PMID- 15475499
TI  - Endothelial cell superoxide generation: regulation and relevance for
      cardiovascular pathophysiology.
AB  - The endothelial generation of reactive oxygen species (ROS) is important both
      physiologically and in the pathogenesis of many cardiovascular disorders. ROS
      generated by endothelial cells include superoxide (O2-*), hydrogen peroxide
      (H2O2), peroxynitrite (ONOO-*), nitric oxide (NO), and hydroxyl (*OH) radicals.
      The O2-* radical, the focus of the current review, may have several effects
      either directly or through the generation of other radicals, e.g., H2O2 and ONOO
      *. These effects include 1) rapid inactivation of the potent signaling molecule
      and endothelium-derived relaxing factor NO, leading to endothelial dysfunction;
      2) the mediation of signal transduction leading to altered gene transcription and
      protein and enzyme activities ("redox signaling"); and 3) oxidative damage.
      Multiple enzymes can generate O2-*, notably xanthine oxidase, uncoupled NO
      synthase, and mitochondria. Recent studies indicate that a major source of
      endothelial O2-* involved in redox signaling is a multicomponent phagocyte-type
      NADPH oxidase that is subject to specific regulation by stimuli such as
      oscillatory shear stress, hypoxia, angiotensin II, growth factors, cytokines, and
      hyperlipidemia. Depending on the level of oxidants generated and the relative
      balance between pro- and antioxidant pathways, ROS may be involved in cell
      growth, hypertrophy, apoptosis, endothelial activation, and adhesivity, for
      example, in diabetes, hypertension, atherosclerosis, heart failure, and ischemia
      reperfusion. This article reviews our current knowledge regarding the sources of
      endothelial ROS generation, their regulation, their involvement in redox
      signaling, and the relevance of enhanced ROS generation and redox signaling to
      the pathophysiology of cardiovascular disorders where endothelial activation and
      dysfunction are implicated.

PMID- 15475500
TI  - Eating and sleeping--their relationship to ghrelin and leptin.

PMID- 15475501
TI  - PACAP enlightenment of mouse circadian clock.

PMID- 15475502
TI  - Hindbrain contributions to anorexia.

PMID- 15475503
TI  - Rhythms of ghrelin, leptin, and sleep in rats: effects of the normal diurnal
      cycle, restricted feeding, and sleep deprivation.
AB  - To determine the relationships among plasma ghrelin and leptin concentrations and
      hypothalamic ghrelin contents, and sleep, cortical brain temperature (Tcrt), and
      feeding, we determined these parameters in rats in three experimental conditions:
      in free-feeding rats with normal diurnal rhythms, in rats with feeding restricted
      to the 12-h light period (RF), and in rats subjected to 5-h of sleep deprivation
      (SD) at the beginning of the light cycle. Plasma ghrelin and leptin displayed
      diurnal rhythms with the ghrelin peak preceding and the leptin peak following the
      major daily feeding peak in hour 1 after dark onset. RF reversed the diurnal
      rhythm of these hormones and the rhythm of rapid-eye-movement sleep (REMS) and
      significantly altered the rhythm of Tcrt. In contrast, the duration and intensity
      of non-REMS (NREMS) were hardly responsive to RF. SD failed to change leptin
      concentrations, but it promptly stimulated plasma ghrelin and induced eating. SD
      elicited biphasic variations in the hypothalamic ghrelin contents. SD increased
      plasma corticosterone, but corticosterone did not seem to influence either leptin
      or ghrelin. The results suggest a strong relationship between feeding and the
      diurnal rhythm of leptin and that feeding also fundamentally modulates the
      diurnal rhythm of ghrelin. The variations in hypothalamic ghrelin contents might
      be associated with sleep-wake activity in rats, but, unlike the previous
      observations in humans, obvious links could not be detected between sleep and the
      diurnal rhythms of plasma concentrations of either ghrelin or leptin in the rat.

PMID- 15475504
TI  - Obesity-prone rats have preexisting defects in their counterregulatory response
      to insulin-induced hypoglycemia.
AB  - Rats that develop diet-induced obesity (DIO) on a 31% fat [high-energy (HE)] diet
      have defective sensing and responding to altered glucose levels compared with
      diet-resistant (DR) rats. Thus we postulated that they would also have defective
      counterregulatory responses (CRR) to insulin-induced hypoglycemia (IIH). Chow-fed
      selectively bred DIO and DR rats underwent three sequential 60-min bouts of IIH
      separated by 48 h. Glucose levels fell comparably, but DIO rats had 22-29% lower
      plasma epinephrine (Epi) levels during the first two bouts than DR rats. By the
      third trial, despite comparable Epi levels, DIO rats had lower 30-min glucose
      levels and rebounded less than DR rats 85 min after intravenous glucose. Although
      DIO rats gained more carcass and fat weight after 4 wk on an HE diet than DR
      rats, they were unaffected by prior IIH. Compared with controls, DR rats with
      prior IIH and HE diet had higher arcuate nucleus neuropeptide Y (50%) and
      proopiomelanocortin (POMC; 37%) mRNA and an inverse correlation (r = 0.85; P =
      0.004) between POMC expression and body weight gain on the HE diet. These data
      suggest that DIO rats have a preexisting defect in their CRR to IIH but that IIH
      does not affect the expression of their hypothalamic neuropeptides or weight gain
      as it does in DR rats.

PMID- 15475505
TI  - Effect of age on cutaneous vasoconstrictor responses to norepinephrine in humans.
AB  - To test the hypothesis that cutaneous vasoconstrictor responsiveness to exogenous
      norepinephrine is reduced in older compared with young subjects, dose-response
      relations between norepinephrine and skin blood flow were established. Seven
      doses of norepinephrine (1.10(-8) to 10(-2) log M) were perfused (2 microl/min)
      intradermally (4 min/dose) using cutaneous microdialysis (2 probes/subject). To
      account for possible differences in endogenous norepinephrine between groups, one
      microdialysis probe was perfused with bretylium tosylate to locally block
      noradrenergic vesicle release before establishing the norepinephrine dose
      response relations. Skin blood flow was indexed via laser-Doppler flowmetry
      directly over both microdialysis probe sites and is expressed as cutaneous
      vascular conductance (laser-Doppler flux/mean arterial blood pressure). Local
      skin temperature was maintained at 34 degrees C at both sites throughout the
      protocol. Dose-response relation between norepinephrine and cutaneous vascular
      conductance was similar between control and bretylium-pretreated sites in young
      subjects (EC50 = -5.18 +/- 0.27 and -5.03 +/- 0.27 log M, respectively). In
      contrast, the dose-response relation was significantly shifted to the right
      (i.e., a higher dose of norepinephrine was needed to produce the same
      vasoconstrictor response) in the bretylium-pretreated site in older subjects
      (EC50 = -5.46 +/- 0.23 and -4.53 +/- 0.23 log M, respectively). Significant
      increases in EC50 were observed in older compared with young subjects at the
      bretylium-pretreated but not the control sites. These data indicate that
      cutaneous vasoconstrictor responsiveness is decreased in older subjects when
      endogenous release of norepinephrine is antagonized. Furthermore, these findings
      suggest that differences in presynaptic norepinephrine release between older and
      younger subjects are profound enough to affect dose-response relations between
      norepinephrine and cutaneous vascular conductance.

PMID- 15475506
TI  - Nerve regeneration-induced recovery of quinine avoidance after complete gustatory
      deafferentation of the tongue.
AB  - The concentration-dependent decrease in quinine licking by rats is substantially
      attenuated by combined bilateral transection of the chorda tympani (CT) and
      glossopharyngeal (GL) nerves, but transection of either nerve alone produces
      marginal impairments at most. Here we tested whether regeneration of one or both
      of these nerves after combined transection would result in recovery of taste
      avoidance. Water-restricted rats were presented with a series of brief-access (5
      s) taste trials (water and 0.003-3.0 mM quinine-HCl) in a 5-day test block of 40
      min sessions both before nerve transection and starting 75-77 days after
      transection. Licking avoidance returned to presurgical levels when both nerves
      were allowed to regenerate. When only the GL was allowed to regenerate,
      performance did not differ from that of sham-transected animals. This suggests
      that even after considerable gustatory deafferentation, regeneration has the
      capacity to restore normal taste-guided behavior. Surprisingly, when only the CT
      was allowed to regenerate, avoidance behavior was severely impaired and was not
      different from that of rats in which regeneration of both nerves was prevented.
      Taking into account prior findings, it appears that the absence of the GL in the
      presence of an intact CT is fundamentally different from the absence of the GL in
      the presence of a regenerated CT with respect to some taste functions. This
      represents the first reported instance to our knowledge in which the capacity of
      a regenerated nerve to maintain taste-guided behavior was distinctly different
      from that of an intact nerve in a rodent model.

PMID- 15475508
TI  - Anterior pituitary hormones: development of a bioassay leading to the discovery
      of prolactin.

PMID- 15475509
TI  - Adrenal cortex: scalpels, syringes, and separatory funnels.

PMID- 15475510
TI  - Discovery of the luteinizing hormone of the anterior pituitary gland.

PMID- 15475511
TI  - Anaplerotic input is sufficient to induce time-dependent potentiation of insulin
      release in rat pancreatic islets.
AB  - Nutrients that induce biphasic insulin release, such as glucose and leucine,
      provide acetyl-CoA and anaplerotic input in the beta-cell. The first phase of
      release requires increased ATP production leading to increased intracellular
      Ca(2+) concentration ([Ca(2+)](i)). The second phase requires increased
      [Ca(2+)](i) and anaplerosis. There is strong evidence to indicate that the second
      phase is due to augmentation of Ca(2+)-stimulated release via the K(ATP) channel
      independent pathway. To test whether the phenomenon of time-dependent
      potentiation (TDP) has similar properties to the ATP-sensitive K(+) channel
      independent pathway, we monitored the ability of different agents that provide
      acetyl-CoA and anaplerotic input or both of these inputs to induce TDP. The
      results show that anaplerotic input is sufficient to induce TDP. Interestingly,
      among the agents tested, the nonsecretagogue glutamine, the nonhydrolyzable
      analog of leucine aminobicyclo[2.2.1]heptane-2-carboxylic acid, and succinic acid
      methyl ester all induced TDP, and all significantly increased alpha-ketoglutarate
      levels in the islets. In conclusion, anaplerosis that enhances the supply and
      utilization of alpha-ketoglutarate in the tricarboxylic acid cycle appears to
      play an essential role in the generation of TDP.

PMID- 15475512
TI  - Neural regulation of glucagon-like peptide-1 secretion in pigs.
AB  - Glucagon-like peptide (GLP)-1 is secreted rapidly from the intestine
      postprandially. We therefore investigated its possible neural regulation. With
      the use of isolated perfused porcine ileum, GLP-1 secretion was measured in
      response to electrical stimulation of the mixed, perivascular nerve supply and
      infusions of neuroactive agents alone and in combination with different blocking
      agents. Electrical nerve stimulation inhibited GLP-1 secretion, an effect
      abolished by phentolamine. Norepinephrine inhibited secretion, and phentolamine
      abolished this effect. GLP-1 secretion was stimulated by isoproterenol (abolished
      by propranolol). Acetylcholine stimulated GLP-1 secretion, and atropine blocked
      this effect. Dimethylphenylpiperazine stimulated GLP-1 secretion. In chloralose
      anesthetized pigs, however, electrical stimulation of the vagal trunks at the
      level of the diaphragm had no effect on GLP-1 or GLP-2 and weak effects on
      glucose-dependent insulinotropic peptide and somatostatin secretion, although
      this elicited a marked atropine-resistant release of the neuropeptide vasoactive
      intestinal polypeptide to the portal circulation. Thus GLP-1 secretion is
      inhibited by the sympathetic nerves to the gut and may be stimulated by intrinsic
      cholinergic nerves, whereas the extrinsic vagal supply has no effect.

PMID- 15475514
TI  - Ca-induced Ca release: lessons regarding cell models.

PMID- 15475515
TI  - New insights into the molecular and cellular workings of the cardiac Na+/Ca2+
      exchanger.
AB  - The cardiac Na+/Ca2+ exchanger (NCX1) is almost certainly the major Ca2+
      extrusion mechanism in cardiac myocytes, although the driving force for Ca2+
      extrusion is quite small. To explain multiple recent results, it is useful to
      think of the exchanger as a slow Ca2+ buffer that can reverse its function
      multiple times during the excitation-contraction cycle (ECC). An article by the
      group of John Reeves brings new insights to this function by analyzing the role
      of regulatory domains of NCX1 that mediate its activation by a rise of
      cytoplasmic Ca2+. It was demonstrated that the gating reactions are operative
      just in the physiological range of Ca2+ changes, a few fold above resting Ca2+
      level, and that they prevent the exchanger from damping out the influence of
      mechanisms that transiently increase Ca2+ levels. Furthermore, exchangers with
      deleted regulatory domains are shown to reduce resting Ca2+ to lower levels than
      achieved by wild-type exchangers. A study by the group of Kenneth Philipson
      demonstrated that the NCX1 regulatory domain can bind and respond to Ca2+ changes
      on the time scale of the ECC in rat myocytes. At the same time, studies of
      transgenic mice and NCX1 knockout mice generated by the Philipson group revealed
      that large changes of NCX1 activity have rather modest effects on ECC. Simple
      simulations predict these results very well: murine cardiac ECC is very sensitive
      to small changes of the Na+ gradient, very sensitive to changes of the
      sarcoplasmic reticulum Ca2+ pump activity, and very insensitive to changes of
      NCX1 activity. It is speculated that the NCX1 gating reactions not only regulate
      coupled 3Na+:1Ca2+ exchange but also control the exchanger's Na+ leak function
      that generates background Na+ influx and depolarizing current in cardiac
      myocytes.

PMID- 15475516
TI  - Gq/G13 signaling by ET-1 in smooth muscle: MYPT1 phosphorylation via ETA and CPI
      17 dephosphorylation via ETB.
AB  - We analyzed the signaling pathways initiated by endothelin receptors ETA and ETB
      in intestinal circular and longitudinal smooth muscle cells. The response to
      endothelin-1 (ET-1) consisted of two phases in both cell types. The initial,
      transient phase of contraction and phosphorylation of 20-kDa myosin light chain
      (MLC20) was mediated additively by ETA and ETB receptors and initiated by Galphaq
      , Ca2+/calmodulin-dependent activation of MLC kinase. In contrast, the sustained
      phase was mediated selectively by ETA receptors via a pathway involving
      sequential activation of Galpha13, RhoA, and Rho kinase, resulting in
      phosphorylation of MYPT1 at Thr696 and phosphorylation of MLC20. Although PKC was
      activated, CPI-17 was not phosphorylated and hence did not contribute to
      inhibition of MLC phosphatase. The absence of CPI-17 phosphorylation by PKC
      reflected active dephosphorylation of CPI-17 by protein phosphatase 2A (PP2A).
      PP2A was activated via a pathway involving ETB-dependent stimulation of p38 MAPK
      activity. CPI-17 phosphorylation was unmasked in the presence of the ETB
      antagonist BQ-788, but not the ETA antagonist BQ-123, and in the presence of a
      low concentration of okadaic acid, which selectively inactivates PP2A. The
      resultant phosphorylation of CPI-17 was blocked by bisindolylmaleimide, providing
      direct confirmation that it was PKC dependent. We conclude that the two phases of
      the intestinal smooth muscle response to ET-1 involve distinct receptors, G
      proteins, and signaling pathways. The sustained response is mediated via
      selective ETA-dependent phosphorylation of MYPT1. In contrast, ETB initiates an
      inhibitory pathway involving p38 MAPK-dependent activation of PP2A that causes
      dephosphorylation of CPI-17.

PMID- 15475517
TI  - Opposite effect of cAMP signaling in endothelial barriers of different origin.
AB  - cAMP-mediated signaling mechanisms may destabilize or stabilize the endothelial
      barrier, depending on the origin of endothelial cells. Here, microvascular
      coronary [coronary endothelial cells (CEC)] and macrovascular aortic endothelial
      cell (AEC) monolayers with opposite responses to cAMP were analyzed.
      Macromolecule permeability, isometric force, activation state of contractile
      machinery [indicated by phosphorylation of regulatory myosin light chains (MLC),
      activity of MLC kinase, and MLC phosphatase], and dynamic changes of adhesion
      complex proteins (translocation of VE-cadherin and paxillin) were determined.
      cAMP signaling was stimulated by the adenosine receptor agonist 5'-N
      (ethylcarboxamido)-adenosine (NECA), the beta-adrenoceptor agonist isoproterenol
      (Iso), or by the adenylyl cyclase activator forskolin (FSK). Permeability was
      increased in CEC and decreased in AEC on stimulation with NECA, Iso, or FSK. The
      effects could be inhibited by the PKA inhibitor Rp-8-CPT-cAMPS and imitated by
      the PKA activator Sp-cAMPS. Under cAMP/PKA-dependent stimulation, isometric force
      and MLC phosphorylation were reduced in monolayers of either cell type, due to an
      activation of MLC phosphatase. In CEC but not in AEC, FSK induced delocalization
      of VE-cadherin and paxillin from cellular adhesion complexes as indicated by cell
      fractionation and immunofluorescence microscopy. In conclusion, decline in
      contractile activation and isometric force contribute to cAMP/PKA-mediated
      stabilization of barrier function in AEC. In CEC, this stabilizing effect is
      overruled by cAMP-induced disintegration of cell adhesion structures.

PMID- 15475518
TI  - Connexins are mechanosensitive.
AB  - Connexins form gap junction channels that provide a hydrophilic path between cell
      interiors. Some connexins, particularly the lens connexins, Cx46 and Cx50 and
      their orthologs, can form functional hemichannels in nonjunctional membranes.
      These hemichannels are a nonselective conduit to the extracellular medium and may
      jeopardize cell survival. The physiological function of hemichannels has remained
      elusive, but it has been postulated that hemichannels are involved in ATP-release
      caused by mechanical stimulation. Here we show with single-channel and whole cell
      electrophysiological studies that Cx46 hemichannels are mechanosensitive, like
      other families of ion channels and membrane-bound enzymes. The hemichannel
      response to mechanical stress is bipolar. At negative potentials stress opens the
      channel, and at positive potentials stress closes it. Physiologically, Cx46
      hemichannels may assist accommodation of the ocular lens by providing a transient
      path for volume flow as the lens changes shape.

PMID- 15475519
TI  - Transient outward current carried by inwardly rectifying K+ channels in guinea
      pig ventricular myocytes dialyzed with low-K+ solution.
AB  - There have been periodic reports of nonclassic (4-aminopyridine insensitive)
      transient outward K+ current in guinea pig ventricular myocytes, with the most
      recent one describing a novel voltage-gated inwardly rectifying type. In the
      present study, we have investigated a transient outward current that overlaps
      inward Ca2+ current (I(Ca,L)) in myocytes dialyzed with 10 mM K+ solution and
      superfused with Tyrode's solution. Although depolarizations from holding
      potential (Vhp) -40 to 0 mV elicited relatively small inward I(Ca,L) in these
      myocytes, removal of external K+ or addition of 0.2 mM Ba2+ more than doubled the
      amplitude of the current. The basis of the enhancement of I(Ca,L) was the
      suppression of a large transient outward K+ current. Similar enhancement was
      observed when Vhp was moved to -80 mV and test depolarizations were preceded by
      short prepulses to -40 mV. Investigation of the time and voltage properties of
      the outward K+ transient indicated that it was inwardly rectifying and unlikely
      to be carried by voltage-gated channels. The outward transient was attenuated in
      myocytes dialyzed with high-Mg2+ solution, accelerated in myocytes dialyzed with
      100 microM spermine solution, and abolished with time in myocytes dialyzed with
      ATP-free solution. These and other findings suggest that the outward transient is
      a component of classic "time-independent" inwardly rectifying K+ current.

PMID- 15475520
TI  - Heat shock regulates the respiration of cardiac H9c2 cells through upregulation
      of nitric oxide synthase.
AB  - Mild and nonlethal heat shock (i.e., hyperthermia) is known to protect the
      myocardium and cardiomyocytes against ischemic injury. In the present study, we
      have shown that heat shock regulates the respiration of cultured neonatal
      cardiomyocytes (cardiac H9c2 cells) through activation of nitric oxide synthase
      (NOS). The respiration of cultured cardiac H9c2 cells subjected to mild heat
      shock at 42 degrees C for 1 h was decreased compared with that of control. The O2
      concentration at which the rate of O2 consumption is reduced to 50% was increased
      in heat-shocked cells, indicating a lowering of O2 affinity in the mitochondria.
      Western blot analyses showed a fourfold increase in the expression of heat shock
      protein (HSP) 90 and a twofold increase in endothelial NOS (eNOS) expression in
      the heat-shocked cells. Immunoblots of eNOS, inducible NOS (iNOS), and neuronal
      NOS (nNOS) in the immunoprecipitate of HSP90 of heat-shocked cells showed that
      there was a sevenfold increase in eNOS and no changes in iNOS and nNOS. Confocal
      microscopic analysis of cells stained with the NO-specific fluorescent dye 4,5
      diaminofluorescein diacetate showed higher levels of NO production in the heat
      shocked cells than in control cells. The results indicate that heat shock-induced
      HSP90 forms a complex with eNOS and activates it to increase NO concentration in
      the cardiac H9c2 cells. The generated NO competitively binds to the complexes of
      the respiratory chain of the mitochondria to downregulate O2 consumption in heat
      shocked cells. On the basis of these results, we conclude that myocardial
      protection by hyperthermia occurs at least partly by the pathway of HSP90
      mediated NO production, leading to subsequent attenuation of cellular
      respiration.

PMID- 15475522
TI  - Ca-induced Ca release: lessons regarding cell models.

PMID- 15475523
TI  - Microvascular permeability, ultrafiltration, and restricted diffusion.

PMID- 15475524
TI  - Eugene M. Landis and the physiology of the microcirculation.

PMID- 15475525
TI  - Berne's adenosine hypothesis of coronary blood flow control.

PMID- 15475526
TI  - Collateral damage: cardiovascular consequences of chronic sympathetic activation
      with human aging.
AB  - Adult aging in humans is associated with marked and sustained increases in
      sympathetic nervous system (SNS) activity to several peripheral tissues,
      including the heart, the gut-liver circulation, and skeletal muscle. This chronic
      activation of the peripheral SNS likely is, at least in part, a primary response
      of the central nervous system to stimulate thermogenesis to prevent further fat
      storage in the face of increasing adiposity with aging. However, as has been
      proposed in obesity hypertension, this tonic activation of the peripheral SNS has
      a number of adverse secondary cardiovascular consequences. These include chronic
      reductions in leg blood flow and vascular conductance, increased tonic support of
      arterial blood pressure, reduced limb and systemic alpha-adrenergic
      vasoconstrictor responsiveness, impaired baroreflex buffering, large conduit
      artery hypertrophy, and decreased vascular and cardiac responsiveness to beta
      adrenergic stimulation. These effects of chronic age-associated SNS activation on
      the structure and function of the cardiovascular system, in turn, may have
      important implications for the maintenance of physiological function and
      homeostasis, as well as the risk of developing clinical cardiovascular and
      metabolic diseases in middle-aged and older adults.

PMID- 15475527
TI  - Muscle mechanoreceptor sensitivity in heart failure.
AB  - Prior work in animals suggests that muscle mechanoreceptor control of sympathetic
      activation (MSNA) during exercise in heart failure (HF) is heightened and that
      muscle mechanoreceptors are sensitized by metabolic by-products. We sought to
      determine whether 1) muscle mechanoreceptor control of MSNA is enhanced in HF
      patients and 2) lactic acid sensitizes muscle mechanoreceptors during rhythmic
      handgrip (RHG) exercise in healthy humans and patients with HF. Dichloroacetate
      (DCA), which reduces the production of lactic acid, or saline control was infused
      in 12 patients with HF and 13 controls during RHG. MSNA was recorded
      (microneurography). After saline was administered and during exercise thereafter,
      MSNA increased earlier in HF compared with controls, consistent with baseline
      heightened mechanoreceptor sensitivity. In both HF and controls, MSNA increased
      during the 3-min exercise protocol, consistent with further sensitization of
      muscle mechanoreceptors by metabolic by-product(s). During posthandgrip
      circulatory arrest, MSNA returned rapidly to baseline levels, excluding the
      muscle metaboreceptors as mediators of the sympathetic excitation during RHG. To
      isolate muscle mechanoreceptors from central command, we utilized passive
      exercise in 8 HF and 11 controls, and MSNA was recorded. MSNA increased
      significantly during passive exercise in HF but not in controls. In conclusion,
      muscle mechanoreceptors mediate the increase in MSNA during low-level RHG
      exercise in healthy humans, and this muscle mechanoreceptor control is augmented
      further in HF. Neither lactate generation nor the fall in pH during RHG plays a
      central role in muscle mechanoreceptor sensitization. Finally, muscle
      mechanoreceptors in patients with HF have heightened basal sensitivity to
      mechanical stimuli resulting in exaggerated early increases in MSNA.

PMID- 15475528
TI  - Cyclooxygenase products sensitize muscle mechanoreceptors in healthy humans.
AB  - Evidence in healthy animals and humans is accumulating that the muscle
      mechanoreceptors play an important role in mediating sympathetic activation
      during exercise, especially rhythmic exercise. Furthermore, muscle
      mechanoreceptors appear to be sensitized acutely during exercise by metabolic by
      products, although the identity of these by-products remains unknown. The purpose
      of this study was to determine whether the metabolic by-products 1)
      prostaglandins and/or 2) adenosine sensitize muscle mechanoreceptor control of
      muscle sympathetic nerve activity (MSNA) in normal humans during rhythmic
      exercise. MSNA was recorded using microneurography. Muscle mechanoreceptors were
      activated by low-level rhythmic forearm exercise for 3 min. In 16 healthy humans,
      intra-arterial indomethacin was infused into the exercising arm to inhibit
      synthesis of cyclooxygenase products. In 18 healthy humans, intra-arterial
      aminophylline was infused into the exercising arm to block adenosine receptors.
      During saline control, MSNA increased significantly during exercise. Inhibition
      of cyclooxygenase during exercise dramatically and virtually completely
      eliminated the reflex sympathetic activation. Inhibition of adenosine receptors
      with aminophylline had no effect on the sympathetic activation during muscle
      mechanoreceptor stimulation. In conclusion, muscle mechanoreceptors are
      sensitized by cyclooxygenase products, but not by adenosine, during 3 min of low
      level rhythmic handgrip exercise in healthy humans. Further studies of other
      metabolic by-products and of patients with enhanced muscle mechanoreceptor
      sensitivity, such as patients with heart failure, are warranted.

PMID- 15475529
TI  - Loss of bone minerals and strength in rats with aldosteronism.
AB  - Congestive heart failure (CHF) is a clinical syndrome with origins rooted in a
      salt-avid state largely mediated by effector hormones of the circulating renin
      angiotensin-aldosterone system. Other participating neurohormones include
      catecholamines, endothelin-1, and arginine vasopressin. CHF is accompanied by a
      systemic illness of uncertain causality. Features include the appearance of
      oxidative/nitrosative stress and a wasting of tissues including bone. Herein we
      hypothesized that inappropriate (relative to dietary Na+) elevations in plasma
      aldosterone (Aldo) contribute to an altered redox state, augmented excretion of
      divalent cations, and in turn, a loss of bone minerals and strength. In
      uninephrectomized rats that received chronic Aldo and 1% NaCl treatment for 4-6
      wk, we monitored plasma alpha1-antiproteinase activity, which is an inverse
      correlate of oxidative/nitrosative stress; plasma concentrations of ionized Mg2+
      and Ca2+; urinary Mg2+ and Ca2+ excretion; and bone mineral composition and
      strength to flexure stress. Compared with controls, we found reductions in plasma
      alpha1-antiproteinase activity and ionized Mg2+ and Ca2+ together with
      persistently elevated urinary Mg2+ and Ca2+ excretion, a progressive loss of bone
      mineral density and content with reduced Mg2+ and Ca2+ concentrations, and a
      reduction in cortical bone strength. Thus the hypermagnesuria and hypercalciuria
      that accompany chronic Aldo-1% NaCl treatment contribute to the systemic
      appearance of oxidative/nitrosative stress and a wasting of bone minerals and
      strength.

PMID- 15475530
TI  - Validation of echocardiographic methods for assessing left ventricular
      dysfunction in rats with myocardial infarction.
AB  - The rat infarct model is widely used in heart failure research, but few
      echocardiographic indexes of left ventricular (LV) function are validated in this
      model. Accordingly, the objective of this study was to validate a 13-segment LV
      wall motion score index (WMSI) and the myocardial performance index (MPI) in
      infarcted rats. Twenty-nine male Wistar rats underwent left coronary artery
      ligation or sham operation and were evaluated with two-dimensional and Doppler
      flow echocardiography 8 wk later. After echocardiography, invasive indexes were
      obtained using a high-fidelity catheter. WMSI and MPI were correlated with the
      invasive and noninvasive measurements of LV function. WMSI and MPI significantly
      correlated directly with end-diastolic pressure (r=0.72 and 0.42 for WMSI and
      MPI, respectively) and the time constant of isovolumic relaxation (r=0.68 and
      0.48) and inversely with peak rate of rise of LV pressure (+dP/dt; r=-0.68 and 
      0.50), peak rate of decline in LV pressure (r=-0.57 and -0.44), LV developed
      pressure (r=-0.58 and -0.42), area fractional shortening (r=-0.85 and -0.53), and
      cardiac index (r=-0.74 and -0.74). Stepwise linear regression analyses revealed
      that LV end-diastolic pressure, +dP/dt, area fractional shortening, and cardiac
      index were independent determinants of WMSI (r=0.994) and that cardiac index and
      +dP/dt were independent determinants of MPI (r=0.781). We conclude that the 13
      segment WMSI and MPI are reproducible and correlate strongly with established
      echocardiographic and invasive indexes of systolic and diastolic function. These
      findings support the use of WMSI and MPI as indexes of global LV function in the
      rat infarction model of heart failure.

PMID- 15475531
TI  - Triggered activity due to delayed afterdepolarizations in sites of focal origin
      of ischemic ventricular tachycardia.
AB  - This study for the first time systematically evaluated the site of origin of
      focal ventricular tachycardia (VT) induced 1-3 h after acute coronary artery
      ligation in dogs. We determined whether delayed afterdepolarizations (DADs) and
      triggered activity (TA) are more often recorded from ischemic endocardium excised
      from focal sites of VT origin. A total of 145 alpha-chloralose-anesthetized dogs
      were studied: in 54 dogs without inducible VT, normal or ischemic endocardium was
      investigated in vitro; in 91 dogs, inducible VT was studied by three-dimensional
      activation mapping, with in vitro study of 51 endocardial foci compared with 40
      endocardial ischemic sites not of VT origin. Incidence of DADs (71% vs. 33%, P
      <0.05) and TA (32% vs. 11%, P <0.05) was greater in ischemic than in normal
      Purkinje tissues. Purkinje sites of origin of focal VT demonstrated the greatest
      frequency of DADs (92%, P <0.05) and TA (75%, P <0.05), with repetitive TA
      predominating. Similar results were obtained in endocardial sites of origin.
      Action potentials were mildly depolarized and prolonged in the focal sites of
      origin. These abnormalities were stable up to 2.5 h of recording. This study
      demonstrated that DADs and TA may underlie a majority of focal VTs in ischemic
      endocardium and Purkinje tissue.

PMID- 15475532
TI  - Brain angiotensin-converting enzyme activity and autonomic regulation in heart
      failure.
AB  - Several recent studies suggest an important role for the brain renin-angiotensin
      system in the pathogenesis of heart failure. Angiotensin-converting enzyme (ACE)
      activity and binding of angiotensin type 1 (AT1) receptors, which mediate the
      central effects of ANG II, are increased in heart failure. The present study
      examined the relationship between brain ACE activity and the autonomic
      dysregulation characteristic of rats with congestive heart failure. Rats with
      heart failure (HF) induced by coronary artery ligation and sham-operated control
      (SHAM) rats were treated with chronic (28 days) third cerebral ventricle
      [intracerebroventricular (ICV)] or intraperitoneal (IP) infusion of a low dose of
      the ACE inhibitor enalaprilat (ENL) or vehicle (VEH). VEH-treated HF rats had
      increased sodium consumption, reduced urine sodium and urine volume, and
      increased sympathetic nerve activity with impaired baroreflex regulation. These
      responses were minimized or prevented by ICV ENL started 24 h after coronary
      ligation. IP ENL at the low dose used in these studies had no beneficial effects
      on HF rats. Neither IP nor ICV ENL had any substantial effect on the SHAM rats.
      The findings confirm a critically important contribution of the brain renin
      angiotensin system to the pathophysiology of congestive heart failure.

PMID- 15475533
TI  - Modulation of control of muscle sympathetic nerve activity during orthostatic
      stress in humans.
AB  - We tested the hypothesis that orthostatic stress would modulate the arterial
      baroreflex (ABR)-mediated beat-by-beat control of muscle sympathetic nerve
      activity (MSNA) in humans. In 12 healthy subjects, ABR control of MSNA (burst
      incidence, burst strength, and total activity) was evaluated by analysis of the
      relation between beat-by-beat spontaneous variations in diastolic blood pressure
      (DAP) and MSNA during supine rest (CON) and at two levels of lower body negative
      pressure (LBNP: -15 and -35 mmHg). At -15 mmHg LBNP, the relation between burst
      incidence (bursts per 100 heartbeats) and DAP showed an upward shift from that
      observed during CON, but the further shift seen at -35 mmHg LBNP was only
      marginal. The relation between burst strength and DAP was shifted upward at -15
      mmHg LBNP (vs. CON) and further shifted upward at -35 mmHg LBNP. At -15 mmHg
      LBNP, the relation between total activity and DAP was shifted upward from that
      obtained during CON and further shifted upward at -35 mmHg LBNP. These results
      suggest that ABR control of MSNA is modulated during orthostatic stress and that
      the modulation is different between a mild (nonhypotensive) and a moderate
      (hypotensive) level of orthostatic stress.

PMID- 15475534
TI  - Mechanism of cardiac depression after trauma-hemorrhage: increased cardiomyocyte
      IL-6 and effect of sex steroids on IL-6 regulation and cardiac function.
AB  - A prolonged depression of cardiovascular function occurs in males after trauma
      hemorrhagic shock (T-H). Although a correlation between increased circulatory IL
      6 levels and poor outcome has been reported after T-H, it remains unknown whether
      T-H increases IL-6 levels locally in cardiomyocytes and whether there is a
      correlation between altered cardiac function and local IL-6 production after T-H.
      T-H was induced in normal, castrated (2 wk before T-H), and 17beta-estradiol (E2)
      treated (0.5 mg sc, 1 wk before T-H) adult male rats. At 2 h after T-H or sham
      operation, cardiac output, heart rate, mean arterial pressure, positive and
      negative first derivative of pressure (+/-dP/dt), stroke volume, and total
      peripheral resistance were determined. Cardiomyocytes were isolated and divided
      into two parts: one was used for measurements of intracellular IL-6 levels using
      fluorescein-activated cell sorting, and the other was used to isolate RNA to
      determine IL-6 gene expression by quantitative real-time PCR. In addition,
      cardiac IL-6 protein levels were measured in freshly isolated hearts by Western
      blotting. Cardiac output, stroke volume, +dP/dt, -dP/dt, and total peripheral
      resistance were markedly altered after T-H. These parameters, except -dP/dt,
      improved significantly in the castrated group; however, all these parameters were
      restored in E2-treated males. Cardiomyocyte IL-6 mRNA expression and
      intracellular IL-6 production increased after T-H. Cardiac IL-6 protein levels
      increased after T-H in freshly isolated heart. Castration and E2 treatment
      attenuated cardiomyocyte intracellular IL-6 levels and cardiac IL-6 protein
      levels after T-H; however, only E2 treatment attenuated cardiomyocyte IL-6 gene
      expression. Thus there is an inverse correlation between cardiomyocyte IL-6
      levels and cardiac function after T-H. The salutary effects of E2 on cardiac
      function after T-H may be due in part to decreased IL-6 synthesis in
      cardiomyocytes.

PMID- 15475535
TI  - Endothelial nitric oxide synthase-deficient mice exhibit increased susceptibility
      to endotoxin-induced acute renal failure.
AB  - Acute renal failure (ARF) in septic patients drastically increases the mortality
      to 50-80%. Nitric oxide (NO) has been shown to be increased in sepsis.
      Endothelial nitric oxide synthase (eNOS) is one of the major regulators of
      arterial blood pressure and regional blood flow; however, its in vivo role in
      septic ARF is still unclear. We hypothesized that eNOS affords a protective
      effect against the renal vasoconstriction during endotoxemia. Because there are
      no specific inhibitors for eNOS, the study was therefore undertaken in eNOS
      knockout mice. There was no significant difference in baseline glomerular
      filtration rate (GFR) between the wild-type mice and the eNOS knockout mice (140
      +/- 10 vs. 157 +/- 18 microl/min, n = 9, P = not significant). However, renal
      blood flow (RBF) was significantly decreased in eNOS knockout mice compared with
      the wild-type controls (0.62 +/- 0.05 ml/min, n = 6 vs. 0.98 +/- 0.13 ml/min, n =
      8, P < 0.05). Mean arterial pressure (MAP) was significantly higher in eNOS
      knockout mice than the wild-type controls (109 +/- 5 vs. 80 +/- 1 mmHg, n = 10, P
      < 0.01). Thus renal vascular resistance (RVR) was much higher in eNOS knockout
      mice than in the wild-type mice (176 +/- 2, n = 6 vs. 82 +/- 1 mmHg.ml(-1).min(
      1), n = 8, P < 0.01). When 1.0 mg/kg LPS was injected, there was no change in MAP
      in either the wild-type (84 +/- 3 mmHg, n = 10) or the eNOS knockout mice (105 +/
      5 mmHg, n = 10). Although GFR (154 +/- 22 microl/min, n = 8) and RBF (1.19 +/-
      0.05 ml/min, n = 9) remained unchanged with the 1.0-mg/kg dose of LPS in the wild
      type mice, GFR (83 +/- 18 vs. 140 +/- 10 microl/min, n = 6, P < 0.01) and RBF
      (0.36 +/- 0.04 vs. 0.62 +/- 0.05 ml/min, n = 6, P < 0.01) decreased significantly
      in the eNOS knockout mice. Fractional excretion of sodium increased significantly
      in eNOS knockout mice during endotoxemia (3.61 +/- 0.78, n = 7 vs. 0.95 +/- 0.14,
      n = 6, P < 0.01), whereas it remained unchanged in the wild-type mice (0.59 +/-
      0.16, n = 9 vs. 0.42 +/- 0.05, n = 6, P = not significant). In summary, eNOS
      knockout mice have increased RVR and are more susceptible to endotoxemic ARF than
      wild-type mice despite higher MAP.

PMID- 15475536
TI  - Introduction to the classic papers commemorating the APS Legacy Project.

PMID- 15475537
TI  - Experimental validation of the countercurrent model of urinary concentration.
AB  - This essay looks at the historical significance of four APS classic papers that
      are freely available online: Jolliffe N, Shannon JA, and Smith HW. The excretion
      of urine in the dog. III. The use of non-metabolized sugars in the measurement of
      the glomerular filtrate. Am J Physiol 100: 301-312, 1932
      (http://ajplegacy.physiology.org/cgi/reprint/100/2/301). Shannon JA. The
      excretion of inulin by the dog. Am J Physiol 112: 405-413, 1935
      (http://ajplegacy.physiology.org/cgi/reprint/112/3/405). Shannon JA and Fisher S.
      The renal tubular reabsorption of glucose in the normal dog. Am J Physiol 122:
      765-774, 1938 (http://ajplegacy.physiology.org/cgi/reprint/122/3/765). Shannon
      JA, Farber S, and Troast L. The measurement of glucose Tm in the normal dog. Am J
      Physiol 133: 752-761, 1941
      (http://ajplegacy.physiology.org/cgi/reprint/133/3/752).

PMID- 15475538
TI  - Two classic papers in acid-base physiology: contributions of R. F. Pitts, R. S.
      Alexander, and W. D. Lotspeich.
AB  - This essay looks at the historical significance of two APS classic papers that
      are freely available online: Pitts RF and Alexander RS. The nature of the renal
      tubular mechanism for acidifying the urine. Am J Physiol 144: 239-254, 1945
      (http://ajplegacy.physiology.org/cgi/reprint/144/2/239). Pitts RF and Lotspeich
      WD. Bicarbonate and the renal regulation of acid base balance. Am J Physiol 147:
      138-154, 1946 (http://ajplegacy.physiology.org/cgi/reprint/147/1/138).

PMID- 15475539
TI  - Micropuncture: unlocking the secrets of renal function.
AB  - This essay looks at the historical significance of five APS classic papers that
      are freely available online: Wearn JT and Richards AN. Observations on the
      composition of glomerular urine, with particular reference to the problem of
      reabsorption in the renal tubules. Am J Physiol 71: 209-227, 1924
      (http://ajplegacy.physiology.org/cgi/reprint/71/1/209). Richards AN and Walker
      AM. Methods of collecting fluid from known regions of the renal tubules of
      Amphibia and of perfusing the lumen of a single tubule. Am J Physiol 118: 111
      120, 1936 (http://ajplegacy.physiology.org/cgi/reprint/118/1/111). Walker AM and
      Hudson CL. The reabsorption of glucose from the renal tubule in Amphibia and the
      action of phlorhizin upon it. Am J Physiol 118: 130-143, 1936
      (http://ajplegacy.physiology.org/cgi/reprint/118/1/130). Walker AM and Oliver J.
      Methods for the collection of fluid from single glomeruli and tubules of the
      mammalian kidney. Am J Physiol 134: 562-579, 1941
      (http://ajplegacy.physiology.org/cgi/reprint/134/3/562). Walker AM, Bott PA,
      Oliver J, and MacDowell MC. The collection and analysis of fluid from single
      nephrons of the mammalian kidney. Am J Physiol 134: 580-595, 1941
      (http://ajplegacy.physiology.org/cgi/reprint/134/3/580).

PMID- 15475540
TI  - The development of clearance methods for measurement of glomerular filtration and
      tubular reabsorption.
AB  - This essay looks at the historical significance of four APS classic papers that
      are freely available online: Jolliffe N, Shannon JA, and Smith HW. The excretion
      of urine in the dog. III. The use of non-metabolized sugars in the measurement of
      the glomerular filtrate. Am J Physiol 100: 301-312, 1932
      (http://ajplegacy.physiology.org/cgi/reprint/100/2/301). Shannon JA. The
      excretion of inulin by the dog. Am J Physiol 112: 405-413, 1935
      (http://ajplegacy.physiology.org/cgi/reprint/112/3/405). Shannon JA and Fisher S.
      The renal tubular reabsorption of glucose in the normal dog. Am J Physiol 122:
      765-774, 1938 (http://ajplegacy.physiology.org/cgi/reprint/122/3/765). Shannon
      JA, Farber S, and Troast L. The measurement of glucose Tm in the normal dog. Am J
      Physiol 133: 752-761, 1941
      (http://ajplegacy.physiology.org/cgi/reprint/133/3/752).

PMID- 15475541
TI  - PDZ interactions and proximal tubular phosphate reabsorption.
AB  - In adults, the extent of renal reabsorption of P(i) and consequently the extent
      of urinary excretion of phosphate are to a large extent determined by the
      abundance of the Na-P(i) cotransporter NaPi-IIa (SLC34A1). Localization of this
      cotransporter is restricted to the apical membrane of proximal tubular cells, and
      its abundance is controlled by a number of factors and pathophysiological
      conditions. To guarantee a proper apical localization and specific regulated
      endocytosis of NaPi-IIa, an orchestrated pattern of protein interactions has to
      be envisaged. Attempts to screen for such interacting proteins resulted in the
      identification of a PDZ domain containing proteins. The purpose of this review is
      to discuss the roles of these PDZ proteins in proximal tubular Na-P(i)
      cotransport.

PMID- 15475542
TI  - Hypertonicity and TonEBP promote development of the renal concentrating system.

PMID- 15475543
TI  - Oxidant stress in kidneys of spontaneously hypertensive rats involves both
      oxidase overexpression and loss of extracellular superoxide dismutase.
AB  - Oxidant stress is an important contributor to renal dysfunction and hypertension.
      We have previously demonstrated that regulation of renal oxygen consumption by
      nitric oxide (NO) is impaired in the kidney of spontaneously hypertensive rats
      (SHR) due to increased superoxide production. We further explored the mechanisms
      of enhanced oxidant stress in the kidney of SHR. Suppression of cortical oxygen
      consumption by bradykinin (BK) or enalaprilat (Enal), which act through
      stimulation of endogenous NO, was impaired in SHR (BK: -14.1 +/- 1.2%; Enal: 
      15.5 +/- 1.2%) and was restored by addition of apocynin, an inhibitor of assembly
      of the NAD(P)H oxidase complex (BK: -21.0 +/- 0.6%; Enal: -25.3 +/- 1.4%),
      suggesting this as the source of enhanced superoxide production. Addition of an
      angiotensin type 1 receptor blocker, losartan, also restored responsiveness to
      control levels (BK: -22.0 +/- 1.1%; Enal: -23.6 +/- 1.3%), suggesting that ANG II
      is responsible for enhanced oxidase activity. A similar defect in responsiveness
      to BK and Enal could be induced in Wistar-Kyoto kidneys by ANG II and was
      reversed by a superoxide scavenger (tempol), apocynin or losartan. Immunoblotting
      of cortical samples demonstrated enhanced expression of endothelial NO synthase
      (eNOS 1.9x) and NAD(P)H oxidase components (gp91(phox) 1.6x and Rac-1 4.5x).
      Expression of SOD-1 and -2 were unchanged, but SOD-3 was significantly decreased
      in SHR (0.5x). Thus NO bioavailability is impaired in SHR owing to an ANG II
      mediated increase in superoxide production in association with enhanced
      expression of NAD(P)H oxidase components, despite increased expression of eNOS.
      Loss of SOD-3, an important superoxide scavenger, may also contribute to enhanced
      oxidant stress.

PMID- 15475545
TI  - Nature vs. nurture: can exercise really alter fiber type composition in human
      skeletal muscle?

PMID- 15475546
TI  - Hypothalamic control of body temperature: insights from the past.

PMID- 15475547
TI  - Comroe's study of aortic chemoreceptors: a path well chosen.

PMID- 15475548
TI  - The significance of the blood gas analyzer.

PMID- 15475549
TI  - First electrodes for blood PO2 and PCO2 determination.

PMID- 15475550
TI  - The paper that completely altered our thinking about cerebral blood flow
      measurement.

PMID- 15475551
TI  - Understanding pulmonary gas exchange: ventilation-perfusion relationships.

PMID- 15475552
TI  - Vascular endothelial growth factor and related molecules in acute lung injury.
AB  - VEGFs and their receptors have been implicated in the regulation of vascular
      permeability in many organ systems, including the lung. Increased permeability
      and interstitial and pulmonary edema are prominent features of acute lung injury
      (ALI)/acute respiratory distress syndrome (ARDS). Extrapolating data from other
      organ systems and animal experiments have suggested that overexpression of VEGF
      functions primarily as proinjurious molecules in the lung. Recent data, from
      animal models as well as from patients with ARDS, have shown decreased levels of
      VEGF in the lung. The role of VEGF and related molecules in ALI/ARDS is,
      therefore, controversial: what has become clear is that there are many unique
      features in the regulation of pulmonary vascular permeability and in VEGF
      expression in the lung. In this review, we explore a growing body of literature
      looking at the expression and function of VEGF and related molecules in different
      models of ALI and in patients with ALI/ARDS. Novel evidence points to a potential
      role of VEGF in promoting repair of the alveolar-capillary membrane during
      recovery from ALI/ARDS. Understanding the role of VEGF in this disease process is
      crucial for developing new therapeutic strategies for ALI/ARDS.

PMID- 15475553
TI  - Capra, eupnea, dyspnea, apnea: respiratory rhythms and the pre-Botzinger complex
      in the goat.

PMID- 15475554
TI  - Absence of left ventricular and arterial adaptations to exercise in
      octogenarians.
AB  - Recent evidence suggests that octogenarians exhibit attenuated adaptations to
      training with a small increase in peak O2 consumption (VO2) that is mediated by a
      modest improvement in cardiac output without an increase in arteriovenous O2
      content difference. This study was designed to determine whether diminished
      increases in peak VO2 and cardiac output in the octogenarians are associated with
      absence of left ventricular and arterial adaptations to exercise training. We
      studied 22 octogenarians (81.9 +/- 3.7 yr, mean +/- SD) randomly assigned a group
      that exercised at an intensity of 82.5 +/- 5% of peak heart rate for 9 mo and 14
      (age 83.1 +/- 4.1) assigned to a control group. Peak VO2 increased 12% in the
      exercise group but decreased slightly (-7%) in the controls. The exercise group
      demonstrated significant but small decreases in the heart rate (6%, P = 0.002)
      and the rate-pressure product (9%, P = 0.004) during submaximal exercise at an
      absolute work rate. Training induced no significant changes in the left
      ventricular size, geometry (wall thickness-to-radius ratio), mass, and function
      assessed with two-dimensional echocardiography or in arterial stiffness evaluated
      with applanation tonometry. Data suggest that the absence of cardiac and arterial
      adaptations may in part account for the limited gain in aerobic capacity in
      response to training in the octogenarians.

PMID- 15475555
TI  - ANG II in the paraventricular nucleus potentiates the cardiac sympathetic
      afferent reflex in rats with heart failure.
AB  - Chronic heart failure (CHF) is characterized by sympathoexcitation, and the
      cardiac sympathetic afferent reflex (CSAR) is a sympathoexcitatory reflex. Our
      previous studies have shown that the CSAR was enhanced in CHF. In addition,
      central angiotensin II (ANG II) is an important modulator of this reflex. This
      study was performed to determine whether the CSAR evoked by stimulation of
      cardiac sympathetic afferent nerves (CSAN) in rats with coronary ligation-induced
      CHF is enhanced by ANG II in the paraventricular nucleus (PVN). Under alpha
      chloralose and urethane anesthesia, renal sympathetic nerve activity (RSNA) was
      recorded. The RSNA responses to electrical stimulation (5, 10, 20, and 30 Hz) of
      the CSAN were evaluated. Bilateral microinjection of the AT1-receptor antagonist
      losartan (50 nmol) into the PVN had no significant effects in the sham group, but
      it abolished the enhanced RSNA response to stimulation in the CHF group.
      Unilateral microinjection of three doses of ANG II (0.03, 0.3, and 3 nmol) into
      the PVN resulted in dose-related increases in the RSNA responses to stimulation.
      Although ANG II also potentiated the RSNA response to electrical stimulation in
      sham rats, the RSNA responses to stimulation after ANG II into the PVN in rats
      with CHF were much greater than in sham rats. The effects of ANG II were
      prevented by pretreatment with losartan into the PVN in CHF rats. These results
      suggest that the central gain of the CSAR is enhanced in rats with coronary
      ligation-induced CHF and that ANG II in the PVN augments the CSAR evoked by CSAN,
      which is mediated by the central angiotensin AT1 receptors in rats with CHF.

PMID- 15475556
TI  - Ventilatory behavior during sleep among A/J and C57BL/6J mouse strains.
AB  - The pattern of breathing during sleep could be a heritable trait. Our intent was
      to test this genetic hypothesis in inbred mouse strains known to vary in
      breathing patterns during wakefulness (Han F, Subramanian S, Dick TE, Dreshaj IA,
      and Strohl KP. J Appl Physiol 91: 1962-1970, 2001; Han F, Subramanian S, Price
      ER, Nadeau J, and Strohl KP, J Appl Physiol 92: 1133-1140, 2002) to determine
      whether such differences persisted into non-rapid eye movement (NREM) and rapid
      eye movement (REM) sleep. Measures assessed in C57BL/6J (B6; Jackson Laboratory)
      and two A/J strains (A/J Jackson and A/J Harlan) included ventilatory behavior
      [respiratory frequency, tidal volume, minute ventilation, mean inspiratory flow,
      and duty cycle (inspiratory time/total breath time)], and metabolism, as
      performed by the plethsmography method with animals instrumented to record EEG,
      electromyogram, and heart rate. In all strains, there were reductions in minute
      ventilation and CO2 production in NREM compared with wakefulness (P < 0.001) and
      a further reduction in REM compared with NREM (P < 0.001), but no state-by-stain
      interactions. Frequency showed strain (P < 0.0001) and state-by-strain
      interactions (P < 0.0001). The A/J Jackson did not change frequency in REM vs.
      NREM [141 +/- 15 (SD) vs. 139 +/- 14 breaths/min; P = 0.92], whereas, in the A/J
      Harlan, it was lower in REM vs. NREM (168 +/- 14 vs. 179 +/- 12 breaths/min; P =
      0.0005), and, in the B6, it was higher in REM vs. NREM (209 +/- 12 vs. 188 +/- 13
      breaths/min; P < 0.0001). Heart rate exhibited strain (P = 0.003), state (P <
      0.0001), and state-by-strain interaction (P = 0.017) and was lower in NREM sleep
      in the A/J Harlan (P = 0.035) and B6 (P < 0.0001). We conclude that genetic
      background affects features of breathing during NREM and REM sleep, despite broad
      changes in state, metabolism, and heart rate.

PMID- 15475557
TI  - Signals and mechanisms of compensatory lung growth.
AB  - Growth of the lung involves unique structure-function interactions not seen in
      solid organs. Mechanical feedback between the lung and thorax constitutes a major
      signal that sustains developmental as well as compensatory lung growth. After the
      loss of lung units as by pneumonectomy (PNX), increased mechanical stress and
      strain on the remaining units induce adaptive responses to augment oxygen
      transport, including 1) recruitment of alveolar-capillary reserves, 2) remodeling
      of existing tissue, and 3) regenerative growth of acinar tissue when strain
      exceeds a critical threshold. Alveolar hypoxia, hormones, and growth factors may
      feed into the mechanical feedback system to modify an existing growth response
      but are unlikely to initiate compensatory growth in the absence of sufficient
      mechanical signals. Whereas endogenous post-PNX alveolar growth preserves normal
      structure-function relationships, experimental manipulation of selected metabolic
      pathways can distort these relationships. Finally, PNX widens the disparity
      between the rapidly adapting acini and slowly adapting conducting airways and
      blood vessels, leading to disproportionate airflow and hemodynamic dysfunction
      and secondary hypertrophy of the right ventricle and respiratory muscles that
      limits overall organ function despite regeneration of gas exchange tissue. These
      are key concepts to consider when formulating approaches to stimulate or augment
      compensatory growth in chronic lung disease.

PMID- 15475558
TI  - Vascular remodeling in the circulations of the lung.
AB  - The lung is unique in its double sources of perfusion from the pulmonary and
      systemic circulations. One striking difference between the two circulations is
      the capacity for angiogenesis. The bronchial circulation has a capacity that
      seems quite similar to all systemic arteries, whereas the pulmonary circulation
      seems relatively inert in this regard. Extra-alveolar pulmonary arteries can grow
      somewhat in length, and septal capillaries seem to have the capability of
      reforming, but these processes do not seem to occur with nearly the same
      intensity associated with the bronchial arteries. In this review, we emphasize
      these differences between the two circulations of the lung, anticipating that
      future research will allow more focused probing into the molecular signaling that
      regulates the novel mechanistic and pathological pathways of each.

PMID- 15475560
TI  - What mechanism is responsible for the decreased BE/[La] ratio in exercise-induced
      metabolic acidosis?

PMID- 15475561
TI  - Quantitative analysis of translesion DNA synthesis across a benzo[a]pyrene
      guanine adduct in mammalian cells: the role of DNA polymerase kappa.
AB  - Replication across unrepaired DNA lesions in mammalian cells is effected
      primarily by specialized, low fidelity DNA polymerases. We studied translesion
      DNA synthesis (TLS) across a benzo[a]pyrene-guanine (BP-G) adduct, a major
      mutagenic DNA lesion generated by tobacco smoke. This was done using a
      quantitative assay that measures TLS indirectly, by measuring the recovery of
      gapped plasmids transfected into cultured mammalian cells. Analysis of PolK(+/+)
      mouse embryo fibroblasts (MEFs) showed that TLS across the BP-G adduct occurred
      with an efficiency of 48 +/- 4%, which is an order of magnitude higher than in
      Escherichia coli. In PolK(-/-) MEFs, bypass was 16 +/- 1%, suggesting that at
      least two-thirds of the BP-G adducts in MEFs were bypassed exclusively by
      polymerase kappa (polkappa). In contrast, poleta was not required for bypass
      across BP-G in a human XP-V cell line. Analysis of misinsertion specificity
      across BP-G revealed that bypass was more error-prone in MEFs lacking polkappa.
      Expression of polkappa from a plasmid introduced into PolK(-/-) MEFs restored
      both the extent and fidelity of bypass across BP-G. Polkappa was not required for
      bypass of a synthetic abasic site. In vitro analysis demonstrated efficient
      bypass across BP-G by both polkappa and poleta, suggesting that the biological
      role of polkappa in TLS across BP-G is due to regulation of TLS and not due to an
      exclusive ability to bypass this lesion. These results indicate that BP-G is
      bypassed in mammalian cells with relatively high efficiency and that polkappa
      bypasses BP-G in vivo with higher efficiency and higher accuracy than other DNA
      polymerases.

PMID- 15475562
TI  - Structural basis for the inactivity of human blood group O2 glycosyltransferase.
AB  - The human ABO(H) blood group antigens are carbohydrate structures generated by
      glycosyltransferase enzymes. Glycosyltransferase A (GTA) uses UDP-GalNAc as a
      donor to transfer a monosaccharide residue to Fuc alpha1-2Gal beta-R (H)
      terminating acceptors. Similarly, glycosyltransferase B (GTB) catalyzes the
      transfer of a monosaccharide residue from UDP-Gal to the same acceptors. These
      are highly homologous enzymes differing in only four of 354 amino acids, Arg/Gly
      176, Gly/Ser-235, Leu/Met-266, and Gly/Ala-268. Blood group O usually stems from
      the expression of truncated inactive forms of GTA or GTB. Recently, an O(2)
      enzyme was discovered that was a full-length form of GTA with three mutations,
      P74S, R176G, and G268R. We showed previously that the R176G mutation increased
      catalytic activity with minor effects on substrate binding. Enzyme kinetics and
      high resolution structural studies of mutant enzymes based on the O(2) blood
      group transferase reveal that whereas the P74S mutation in the stem region of the
      protein does not appear to play a role in enzyme inactivation, the G268R mutation
      completely blocks the donor GalNAc-binding site leaving the acceptor binding site
      unaffected.

PMID- 15475563
TI  - Identification of negative residues in the P2X3 ATP receptor ectodomain as
      structural determinants for desensitization and the Ca2+-sensing modulatory
      sites.
AB  - On nociceptive neurons, one important mechanism to generate pain signals is the
      activation of P2X(3) receptors, which are membrane proteins gated by
      extracellular ATP. In the presence of the agonist, P2X(3) receptors rapidly
      desensitize and then recover slowly. One unique property of P2X(3) receptors is
      the recovery acceleration by extracellular Ca(2+) that can play the role of the
      gain-setter of receptor function only when P2X(3) receptors are desensitized. To
      study negatively charged sites potentially responsible for this action of Ca(2+),
      we mutated 15 non-conserved aspartate or glutamate residues in the P2X(3)
      receptor ectodomain with alanine and expressed such mutated receptors in human
      embryonic kidney cells studied with patch clamping. Unlike most mutants, D266A
      (P2X(3) receptor numbering) desensitized very slowly, indicating that this
      residue is important for generating desensitization. Recovery appeared
      structurally distinct from desensitization because E111A and D266A had a much
      faster recovery and D220A and D289A had a much slower one despite their standard
      desensitization. Furthermore, E161A, E187A, or E270A mutants showed lessened
      sensitivity to the action of extracellular Ca(2+), suggesting that these
      determinants were important for the effect of this cation on desensitization
      recovery. This study is the first report identifying several negative residues in
      the P2X(3) receptor ectodomain differentially contributing to the general process
      of receptor desensitization. At least one residue was important to enable the
      development of rapid desensitization, whereas others controlled recovery from it
      or the facilitating action of Ca(2+). Thus, these findings outline diverse
      potential molecular targets to modulate P2X(3) receptor function in relation to
      its functional state.

PMID- 15475564
TI  - An RNA-interacting protein, SYNCRIP (heterogeneous nuclear ribonuclear protein
      Q1/NSAP1) is a component of mRNA granule transported with inositol 1,4,5
      trisphosphate receptor type 1 mRNA in neuronal dendrites.
AB  - mRNA transport and local translation in the neuronal dendrite is implicated in
      the induction of synaptic plasticity. Recently, we cloned an RNA-interacting
      protein, SYNCRIP (heterogeneous nuclear ribonuclear protein Q1/NSAP1), that is
      suggested to be important for the stabilization of mRNA. We report here that
      SYNCRIP is a component of mRNA granules in rat hippocampal neurons. SYNCRIP was
      mainly found at cell bodies, but punctate expression patterns in the proximal
      dendrite were also seen. Time-lapse analysis in living neurons revealed that the
      granules labeled with fluorescent protein-tagged SYNCRIP were transported bi
      directionally within the dendrite at approximately 0.05 microm/s. Treatment of
      neurons with nocodazole significantly inhibited the movement of green fluorescent
      protein-SYNCRIP-positive granules, indicating that the transport of SYNCRIP
      containing granules is dependent on microtubules. The distribution of SYNCRIP
      containing granules overlapped with that of dendritic RNAs and elongation factor
      1alpha. SYNCRIP was also found to be co-transported with green fluorescent
      protein-tagged human staufen1 and the 3'-untranslated region of inositol 1,4,5
      trisphosphate receptor type 1 mRNA. These results suggest that SYNCRIP is
      transported within the dendrite as a component of mRNA granules and raise the
      possibility that mRNA turnover in mRNA granules and the regulation of local
      protein synthesis in neuronal dendrites may involve SYNCRIP.

PMID- 15475565
TI  - Linking alterations in tau phosphorylation and cleavage during neuronal
      apoptosis.
AB  - Neurofibrillary tangles (NFTs) are classic lesions of Alzheimer's disease. NFTs
      are bundles of abnormally phosphorylated tau, the paired helical filaments. The
      initiating mechanisms of NFTs and their role in neuronal loss are still unknown.
      Accumulating evidence supports a role for the activation of proteolytic enzymes,
      caspases, in neuronal death observed in brains of patients with Alzheimer's
      disease. Alterations in tau phosphorylation and tau cleavage by caspases have
      been previously reported in neuronal apoptosis. However, the links between the
      alterations in tau phosphorylation and its proteolytic cleavage have not yet been
      documented. Here, we show that, during staurosporine-induced neuronal apoptosis,
      tau first undergoes transient hyperphosphorylation, which is followed by
      dephosphorylation and cleavage. This cleavage generated a 10-kDa fragment in
      addition to the 17- and 50-kDa tau fragments previously reported. Prior tau
      dephosphorylation by a glycogen synthase kinase-3beta inhibitor, lithium,
      enhanced tau cleavage and sensitized neurons to staurosporine-induced apoptosis.
      Caspase inhibition prevented tau cleavage without reversing changes in tau
      phosphorylation linked to apoptosis. Furthermore, the microtubule depolymerizing
      agent, colchicine, induced tau dephosphorylation and caspase-independent tau
      cleavage and degradation. Both phenomena were blocked by inhibiting protein
      phosphatase 2A (PP2A) by okadaic acid. These experiments indicate that tau
      dephosphorylation precedes and is required for its cleavage and degradation. We
      propose that the absence of cleavage and degradation of hyperphosphorylated tau
      (due to PP2A inhibition) may lead to its accumulation in degenerating neurons.
      This mechanism may contribute to the aggregation of hyperphosphorylated tau into
      paired helical filaments in Alzheimer's disease where reduced PP2A activity has
      been reported.

PMID- 15475566
TI  - A specific endoplasmic reticulum export signal drives transport of stem cell
      factor (Kitl) to the cell surface.
AB  - Stem cell factor, also known as Kit ligand (Kitl), belongs to the family of
      dimeric transmembrane growth factors. Efficient cell surface presentation of Kitl
      is essential for the migration, proliferation, and survival of melanocytes, germ
      cells, hemopoietic stem cells, and mastocytes. Here we demonstrate that
      intracellular transport of Kitl to the cell surface is driven by a motif in the
      cytoplasmic tail that acts independently of the previously described basolateral
      sorting signal. Transport of Kitl to the cell surface is controlled at the level
      of the endoplasmic reticulum (ER) and requires a C-terminal valine residue
      positioned at a distance of 19-36 amino acids from the border between the
      transmembrane and cytoplasmic domains. Deletion or substitution of the valine
      with other hydrophobic amino acids results in ER accumulation and reduced cell
      surface transport of Kitl at physiological expression levels. When these mutant
      proteins are overexpressed in the ER, they are transported by bulk flow to the
      cell surface albeit at lower efficiency. A fusion construct between Kitl and the
      green fluorescent protein-labeled extracellular domain of a temperature-sensitive
      mutant of vesicular stomatitis virus G protein revealed the valine-dependent
      recruitment into coat protein complex II-coated ER exit sites and vesicular ER to
      Golgi transport in living cells. Thus the C-terminal valine defines a specific ER
      export signal in Kitl. It is responsible for the capture of Kitl at coat protein
      complex II-coated ER exit sites, leading to subsequent cell surface transport
      under physiological conditions.

PMID- 15475567
TI  - Oncogenic and anti-apoptotic activity of NF-kappa B in human thyroid carcinomas.
AB  - Thyroid cancer includes three types of carcinomas classified as differentiated
      thyroid carcinomas (DTC), medullary thyroid carcinomas, and undifferentiated
      carcinomas (UTC). DTC and medullary thyroid carcinomas generally have a good
      prognosis, but UTC are usually fatal. Consequently, there is a need for new
      effective therapeutic modalities to improve the survival of UTC patients. Here we
      show that NF-kappa B is activated in human thyroid neoplasms, particularly in
      undifferentiated carcinomas. Thyroid cell lines, reproducing in vitro the
      different thyroid neoplasias, also show basal NF-kappa B activity and resistance
      to drug-induced apoptosis, which correlates with the level of NF-kappa B
      activation. Activation of NF-kappa B in the DTC cell line NPA renders these cells
      resistant to drug-induced apoptosis. Stable expression of a super-repressor form
      of I kappa B alpha (I kappa B alpha M) in the UTC cell line FRO results in
      enhanced sensitivity to drug-induced apoptosis, to the loss of the ability of
      these cells to form colonies in soft agar, and to induce tumor growth in nude
      mice. In addition, we show that FRO cells display a very low JNK activity that is
      restored in FRO-I kappa B alpha M clones. Moreover, inhibition of JNK activity
      renders FRO-I kappa B alpha M clones resistant to apoptosis induced by
      chemotherapeutic agents. Our results indicate that NF-kappa B plays a pivotal
      role in thyroid carcinogenesis, being required for tumor growth and for
      resistance to drug-induced apoptosis, the latter function very likely through the
      inhibition of JNK activity. Furthermore, the strong constitutive NF-kappa B
      activity in human anaplastic thyroid carcinomas, besides representing a novel
      diagnostic tool, makes NF-kappa B a target for the development of novel
      therapeutic strategies.

PMID- 15475568
TI  - Chemical proteomic analysis reveals alternative modes of action for pyrido[2,3
      d]pyrimidine kinase inhibitors.
AB  - Small molecule inhibitors belonging to the pyrido[2,3-d]pyrimidine class of
      compounds were developed as antagonists of protein tyrosine kinases implicated in
      cancer progression. Derivatives from this compound class are effective against
      most of the imatinib mesylate-resistant BCR-ABL mutants isolated from advanced
      chronic myeloid leukemia patients. Here, we established an efficient proteomics
      method employing an immobilized pyrido[2,3-d]pyrimidine ligand as an affinity
      probe and identified more than 30 human protein kinases affected by this class of
      compounds. Remarkably, in vitro kinase assays revealed that the serine/threonine
      kinases Rip-like interacting caspase-like apoptosis-regulatory protein kinase
      (RICK) and p38alpha were among the most potently inhibited kinase targets. Thus,
      pyrido[2,3-d]pyrimidines did not discriminate between tyrosine and
      serine/threonine kinases. Instead, we found that these inhibitors are quite
      selective for protein kinases possessing a conserved small amino acid residue
      such as threonine at a critical site of the ATP binding pocket. We further
      demonstrated inhibition of both p38 and RICK kinase activities in intact cells
      upon pyrido[2,3-d]pyrimidine inhibitor treatment. Moreover, the established
      functions of these two kinases as signal transducers of inflammatory responses
      could be correlated with a potent in vivo inhibition of cytokine production by a
      pyrido[2,3-d]pyrimidine compound. Thus, our data demonstrate the utility of
      proteomic methods employing immobilized kinase inhibitors for identifying new
      targets linked to previously unrecognized therapeutic applications.

PMID- 15475569
TI  - Development of nonsteroidal anti-inflammatory drug analogs and steroid
      carboxylates selective for human aldo-keto reductase isoforms: potential
      antineoplastic agents that work independently of cyclooxygenase isozymes.
AB  - Human aldo-keto reductases (AKRs) regulate nuclear receptors by controlling
      ligand availability. Enzymes implicated in regulating ligand occupancy and trans
      activation of the nuclear receptors belong to the AKR1C family (AKR1C1-AKR1C3).
      Nuclear receptors regulated by AKR1C members include the steroid hormone
      receptors (androgen, estrogen, and progesterone receptors) and the orphan
      peroxisome proliferator-activated receptor (PPARgamma). In human myeloid leukemia
      (HL-60) cells, ligand access to PPARgamma is regulated by AKR1C3, which diverts
      PGD(2) metabolism away from J-series prostanoids (Desmond et al., 2003).
      Inhibition of AKR1C3 by indomethacin, a nonsteroidal anti-inflammatory drug
      (NSAID), caused PPARgamma-mediated terminal differentiation of the HL-60 cells.
      To discriminate between antineoplastic effects of NSAIDs that are mediated by
      either AKR1C or cyclooxygenase (COX) isozymes, selective inhibitors are required.
      We report a structural series of N-phenylanthranilic acid derivatives and steroid
      carboxylates that selectively inhibit recombinant AKR1C isoforms but do not
      inhibit recombinant COX-1 or COX-2. The inhibition constants, IC(50), K(I)
      values, and inhibition patterns were determined for the NSAID analogs and steroid
      carboxylates against AKR1C and COX isozymes. Lead compounds, 4-chloro-N
      phenylanthranilic acid and 4-benzoyl-benzoic acid for the N-phenylanthranilic
      acid analogs and most steroid carboxylates, exhibited IC(50) values that had
      greater than 500-fold selectivity for AKR1C isozymes compared with COX-1 and COX
      2. Crystallographic and molecular modeling studies showed that the carboxylic
      acid of the inhibitor ligand was tethered by the catalytic Tyr55-OH(2)(+) and
      explained why A-ring substituted N-phenylanthranilates inhibited only AKR1C
      enzymes. These compounds can be used to dissect the role of the AKR1C isozymes in
      neoplastic diseases and may have cancer chemopreventive roles independent of COX
      inhibition.

PMID- 15475570
TI  - Multiple independent functions of arrestins in the regulation of protease
      activated receptor-2 signaling and trafficking.
AB  - The irreversible proteolytic nature of protease-activated receptor-2 (PAR2)
      activation suggests that mechanism(s) responsible for termination of receptor
      signaling are critical determinants of the magnitude and duration of PAR2
      elicited cellular responses. Rapid desensitization of activated G-protein-coupled
      receptors (GPCRs) involves both phosphorylation and binding of arrestins.
      Arrestins also function as scaffolds and transducers of mitogen-activated protein
      (MAP) kinase signaling cascades. The PAR2 cytoplasmic tail (C-tail) contains
      multiple sites of phosphorylation and may be an important determinant for
      arrestin interaction. Desensitization and internalization of activated PAR2 were
      markedly impaired in arrestin-deficient cells compared with wild-type control
      cells. PAR2 C-tail truncation mutants displayed normal agonist-induced
      internalization, caused rapid distribution of betaarr2-GFP to the plasma
      membrane, and desensitized in an arrestin-dependent manner similar to that of
      wild-type PAR2. It is interesting that PAR2 C-tail mutants lost the capacity to
      stably associate with arrestins and consequently, redistributed to endocytic
      vesicles without betaarr2-GFP, whereas internalized wild-type PAR2 remained
      stably associated with betaarr2-GFP in endosomes. Moreover, activated PAR2 caused
      rapid and prolonged activation of endogenous extracellular signal-regulated
      kinase (ERK1/2). It was striking that in arrestin-deficient cells, activated PAR2
      induced an initial peak in ERK1/2 activity that rapidly declined. The inability
      of internalized PAR2 C-tail mutants to stably associate with arrestins also
      resulted in loss of prolonged ERK2 activation. Thus, the PAR2 C-tail regulates
      the stability of arrestin interaction and kinetics of ERK1/2 activation but is
      not essential for desensitization or internalization. These findings further
      suggest that the diverse functions of arrestins in regulating PAR2 signaling and
      trafficking are controlled by multiple independent interactions involving both
      the intracellular loops and the C-tail.

PMID- 15475571
TI  - Ertiprotafib improves glycemic control and lowers lipids via multiple mechanisms.
AB  - Ertiprotafib belongs to a novel class of insulin sensitizers developed for
      treatment of type 2 diabetes. In insulin-resistant rodent models, ertiprotafib
      and a close analog lowered both fasting blood glucose and insulin levels and
      improved glycemic excursion during an oral glucose tolerance test. In addition,
      treatment of rodents improved lipid profiles, with significantly lowered
      triglyceride and free fatty acid levels. These results suggested that this
      therapeutic activity might involve mechanisms in addition to PTP1b inhibition. In
      this study, we demonstrate that ertiprotafib activates peroxisome proliferator
      activated receptor (PPAR)alpha and PPARgamma at concentrations comparable with
      those of known agonists of these regulators. Furthermore, it is able to drive
      adipocyte differentiation of C3H10T(1/2) cells, a hallmark of PPARgamma
      activation. Livers from ertiprotafib-treated animals showed significant induction
      of acyl-CoA oxidase activity, probably caused by PPARalpha engagement in these
      animals. We also show that ertiprotafib inhibits PTP1b in vitro with nonclassic
      kinetics at concentrations above its EC(50) for PPAR agonism. Thus, the complete
      mechanism of action for ertiprotafib and related compounds in vivo may involve
      multiple independent mechanisms, including (but not necessarily limited to) PTP1b
      inhibition and dual PPARalpha/PPARgamma agonism. Ertiprotafib pharmacology and
      interpretation of clinical results must be seen in light of this complexity.

PMID- 15475572
TI  - Receptor endocytosis counteracts the development of opioid tolerance.
AB  - In contrast to endogenous opioids, the highly addictive drug morphine activates
      the mu-opioid receptor without causing its rapid endocytosis. It has recently
      been reported that coapplication of low concentrations of [d-Ala(2),N-Me
      Phe(4),Gly(5)-ol]-enkephalin (DAMGO) facilitates the ability of morphine to
      stimulate mu-opioid receptor endocytosis and prevents the development of morphine
      tolerance in rats. To investigate the clinical relevance of this finding for
      analgesic therapy, the endocytotic efficacies of a series of clinically used
      opioids were determined, and the effect of a combination of these drugs with
      morphine on the mu-opioid receptor endocytosis in receptor-expressing human
      embryonic kidney (HEK) 293 cells was quantified. The combination of morphine and
      opioid drugs with high endocytotic efficacies (e.g., DAMGO, etonitazene,
      sufentanil, beta-endorphin, piritramide, or methadone) did not result in a
      facilitation of morphine-mediated endocytosis but rather in a decrease of the
      receptor endocytosis mediated by the tested opioid drugs. These findings
      demonstrate a partial agonistic effect of morphine on the agonist-induced
      receptor endocytosis. Moreover, we demonstrated that the endocytotic potencies of
      opioid drugs are negatively correlated with their ability to cause receptor
      desensitization and opioid tolerance in HEK 293 cells. These results strongly
      support the hypothesis that mu-opioid receptor endocytosis counteracts receptor
      desensitization and opioid tolerance by inducing fast receptor reactivation and
      recycling. In addition, it is shown that agonist-induced receptor endocytosis
      facilitates the compensatory up-regulation of the cAMP pathway, a cellular
      hallmark of opioid withdrawal. Our findings suggest that opioids with high
      endocytotic efficacies might cause reduced opioid tolerance but can facilitate
      compensatory mechanisms, resulting in an enhanced opioid dependence.

PMID- 15475573
TI  - Vascular endothelial cell cyclic nucleotide phosphodiesterases and regulated cell
      migration: implications in angiogenesis.
AB  - Angiogenesis is necessary during embryonic development and wound healing but can
      be detrimental in pathologies, including cancer. Because initiation of
      angiogenesis involves migration and proliferation of vascular endothelial cells
      (VECs) and cAMP-elevating agents inhibit these events, such agents may represent
      a novel therapeutic avenue to controlling angiogenesis. Intracellular cAMP levels
      are regulated by their synthesis by adenylyl cyclases and hydrolysis by cyclic
      nucleotide phosphodiesterases (PDEs). In this report, we show that human VECs
      express variants of PDE2, PDE3, PDE4, and PDE5 families and demonstrate that the
      levels of these enzymes differ in VECs derived from aorta, umbilical vein, and
      microvascular structures. Selective inhibition of PDE2 did not increase cAMP in
      any VECs, whether in the absence or presence of forskolin, but it did inhibit
      migration of all VECs studied. Inhibition of PDE4 activity decreased migration,
      and in conjunction with forskolin, increased cAMP in all VECs studied. PDE3
      inhibition potentiated forskolin-induced increases in cAMP and inhibited
      migration in VECs derived from aorta and umbilical vein but not in microvascular
      VECs. In experiments with combinations of PDE2, PDE3, and PDE4 inhibitors, a
      complex interaction between the abilities of these agents to limit human VEC
      migration was observed. Overall, our data are consistent with the hypothesis that
      PDE subtype inhibition allows different effects in distinct VEC populations and
      indicate that these agents may represent novel therapeutic agents to limit
      angiogenesis in complex human diseases.

PMID- 15475574
TI  - The rate and equilibrium constants for a multistep reaction sequence for the
      aggregation of superoxide dismutase in amyotrophic lateral sclerosis.
AB  - Mutation-induced aggregation of the dimeric enzyme Cu, Zn superoxide dismutase 1
      (SOD1) has been implicated in the familial form of the disease amyotrophic
      lateral sclerosis, but the mechanism of aggregation is not known. Here, we show
      that in vitro SOD1 aggregation is a multistep reaction that minimally consists of
      dimer dissociation, metal loss from the monomers, and oligomerization of the apo
      monomers: [reaction: see text], where D(holo), M(holo), M(apo), and A are the
      holo-dimer, holo-monomer, apo-monomer, and aggregate, respectively. Under
      aggregation-promoting conditions (pH 3.5), the rate and equilibrium constants
      corresponding to each step are: (i) dimer dissociation, Kd approximately 1
      microM; k(off) approximately 1 x 10(-3) s(-1), k(on) approximately 1 x 10(3) M(
      1).s(-1); (ii) metal loss, Km approximately 0.1 microM, km- approximately 1 x 10(
      3)s(-1), km+ approximately 1 x 10(4) M(-1).s(-1); and (iii) assembly (rate
      limiting step), k(agg) approximately 1 x 10(3) M(-1).s(-1). In contrast, under
      near-physiological conditions (pH 7.8), where aggregation is drastically reduced,
      dimer dissociation is less thermodynamically favorable: Kd approximately 0.1 nM,
      and extremely slow: k(off) approximately 3 x 10(-5) s(-1), k(on) approximately 3
      x 10(5) M(-1).s(-1). Our results suggest that familial amyotrophic lateral
      sclerosis-linked SOD1 aggregation occurs by a mutation-induced increase in dimer
      dissociation and/or increase in apomonomer formation.

PMID- 15475575
TI  - Regulation of the endogenous VEGF-A gene by exogenous designed regulatory
      proteins.
AB  - We describe a facile method to activate or repress transcription of endogenous
      genes in a quantitative and specific manner by treatment with designed regulatory
      proteins (DRPs), in which artificial transcription factors (ATFs) are fused to
      cell-penetrating peptides (CPPs). Penetration of DRPs into cells is mediated by
      an N-terminal CPP fused to a nuclear localization signal; a DNA-binding domain
      and a transactivation domain follow. The DNA-binding domain was targeted to the
      vascular endothelial growth factor (VEGF)-A gene. An agonist DRP was rapidly
      taken up by cells and transported to the nucleus; soon after, the cells began
      transcribing the gene and secreting VEGF-A protein in a dose-dependent manner.
      Multiple copies of a short oligopeptide derived from a minimal transactivation
      domain of human beta-catenin was stronger than VP-16. The SRDX domain from the
      plant transcription factor, SUPERMAN, changed the DRP to a hypoxia-induced
      antagonist of VEGF-A. DRPs combine many of the potential benefits of transgenes
      with those of recombinant proteins.

PMID- 15475576
TI  - The fragile X protein controls microtubule-associated protein 1B translation and
      microtubule stability in brain neuron development.
AB  - The fragile X mental retardation protein (FMRP) is a selective RNA-binding
      protein implicated in regulating translation of its mRNA ligands. The absence of
      FMRP results in fragile X syndrome, one of the leading causes of inherited mental
      retardation. Delayed dendritic spine maturation was found in fragile X mental
      retardation patients as well as in Fmr1 knockout (KO) mice, indicating the
      functional requirement of FMRP in synaptic development. However, the biochemical
      link between FMRP deficiency and the neuronal impairment during brain development
      has not been defined. How FMRP governs normal synapse development in the brain
      remains elusive. We report here that the developmentally programmed FMRP
      expression represses the translation of microtubule associated protein 1B (MAP1B)
      and is required for the accelerated decline of MAP1B during active synaptogenesis
      in neonatal brain development. The lack of FMRP results in misregulated MAP1B
      translation and delayed MAP1B decline in the Fmr1 KO brain. Furthermore, the
      aberrantly elevated MAP1B protein expression leads to abnormally increased
      microtubule stability in Fmr1 KO neurons. Together, these results indicate that
      FMRP plays critical roles in controlling cytoskeleton organization during
      neuronal development, and the abnormal microtubule dynamics is a conceivable
      underlying factor for the pathogenesis of fragile X mental retardation.

PMID- 15475577
TI  - Mammalian class I myosin, Myo1b, is monomeric and cross-links actin filaments as
      determined by hydrodynamic studies and electron microscopy.
AB  - The class I myosin, Myo1b, is a calmodulin- and actin-associated molecular motor
      widely expressed in mammalian tissues. Analytical ultracentrifugation studies
      indicate that Myo1b purified from rat liver has a Stokes radius of 6.7 nm and a
      sedimentation coefficient, s(20,w), of 7.0 S with a predicted molar mass of 213
      kg/mol. These results indicate that Myo1b is monomeric and consists primarily of
      a splice variant having five associated calmodulins. Molecular modeling based on
      the analytical ultracentrifugation studies are supported by electron microscopy
      studies that depict Myo1b as a single-headed, tadpole-shaped molecule with outer
      dimensions of 27.9 x 4.0 nm. Above a certain Myo1b/actin ratio, Myo1b bundles
      actin filaments presumably by virtue of a second actin-binding site. These
      studies provide new information regarding the oligomeric state and morphology of
      Myo1b and support a model in which Myo1b cross-links actin through a cryptic
      actin-binding site.

PMID- 15475578
TI  - Modeling P-loops domain of sodium channel: homology with potassium channels and
      interaction with ligands.
AB  - A large body of experimental data on Na+ channels is available, but the
      interpretation of these data in structural terms is difficult in the absence of a
      high-resolution structure. Essentially different electrophysiological and
      pharmacological properties of Na+ and K+ channels and poor identity of their
      sequences obstruct homology modeling of Na+ channels. In this work, we built the
      P-loops model of the Na+ channel, in which the pore helices are arranged exactly
      as in the MthK bacterial K+ channel. The conformation of the selectivity-filter
      region, which includes residues in positions -2 through +4 from the DEKA locus,
      was shaped around rigid molecules of saxitoxin and tetrodotoxin that are known to
      form multiple contacts with this region. Intensive Monte Carlo minimization that
      started from the MthK-like conformation produced practically identical saxitoxin-
      and tetrodotoxin-based models. The latter was tested to explain a wide range of
      experimental data that were not used at the model building stage. The docking of
      tetrodotoxin analogs unambiguously predicted their optimal orientation and the
      interaction energy that correlates with the experimental activity. The docking of
      mu-conotoxin produced a binding model consistent with experimentally known toxin
      channel contacts. Monte Carlo-minimized energy profiles of tetramethylammonium
      pulled through the selectivity-filter region explain the paradoxical experimental
      data that this organic cation permeates via the DEAA but not the AAAA mutant of
      the DEKA locus. The model is also consistent with earlier proposed concepts on
      the Na+ channel selectivity as well as Ca2+ selectivity of the EEEE mutant of the
      DEKA locus. Thus, the model integrates available experimental data on the Na+
      channel P-loops domain, and suggests that it is more similar to K+ channels than
      was believed before.

PMID- 15475579
TI  - HERG channel (dys)function revealed by dynamic action potential clamp technique.
AB  - The human ether-a-go-go-related gene (HERG) encodes the rapid component of the
      cardiac delayed rectifier potassium current (I(Kr)). Per-Arnt-Sim domain
      mutations of the HERG channel are linked to type 2 long-QT syndrome. We studied
      wild-type and/or type 2 long-QT syndrome-associated mutant (R56Q) HERG current
      (I(HERG)) in HEK-293 cells, at both 23 and 36 degrees C. Conventional voltage
      clamp analysis revealed mutation-induced changes in channel kinetics. To assess
      functional implication(s) of the mutation, we introduce the dynamic action
      potential clamp technique. In this study, we effectively replace the native I(Kr)
      of a ventricular cell (either a human model cell or an isolated rabbit myocyte)
      with I(HERG) generated in a HEK-293 cell that is voltage-clamped by the free
      running action potential of the ventricular cell. Action potential
      characteristics of the ventricular cells were effectively reproduced with wild
      type I(HERG), whereas the R56Q mutation caused a frequency-dependent increase of
      the action potential duration in accordance with the clinical phenotype. The
      dynamic action potential clamp approach also revealed a frequency-dependent
      transient wild-type I(HERG) component, which is absent with R56Q channels. This
      novel electrophysiological technique allows rapid and unambiguous determination
      of the effects of an ion channel mutation on the ventricular action potential and
      can serve as a new tool for investigating cardiac channelopathies.

PMID- 15475580
TI  - Structural variation in human apolipoprotein E3 and E4: secondary structure,
      tertiary structure, and size distribution.
AB  - Human apolipoprotein E (apoE) is a 299-amino-acid protein with a molecular weight
      of 34 kDa. The difference between the apoE3 and apoE4 isoforms is a single
      residue substitution involving a Cys-Arg replacement at residue 112. ApoE4 is
      positively associated with atherosclerosis and late-onset and sporadic
      Alzheimer's disease (AD). ApoE4 and its C-terminal truncated fragments have been
      found in the senile plaques and neurofibrillary tangles in the brain of AD
      patients. However, detail structural information regarding isoform and domain
      interaction remains poorly understood. We prepared full-length, N-, and C
      terminal truncated apoE3 and apoE4 proteins and studied their structural
      variation. Sedimentation velocity and continuous size distribution analysis using
      analytical ultracentrifugation revealed apoE3(72-299) as consisting of a major
      species with a sedimentation coefficient of 5.9. ApoE4(72-299) showed a wider and
      more complicated species distribution. Both apoE3 and E4 N-terminal domain (1
      191) existed with monomers as the major component together with some tetramer.
      The oligomerization and aggregation of apoE protein increased when the C-terminal
      domain (192-271) was incorporated. The structural influence of the C-terminal
      domain on apoE is to assist self-association with no significant isoform
      preference. Circular dichroism and fluorescence studies demonstrated that
      apoE4(72-299) possessed a more alpha-helical structure with more hydrophobic
      residue exposure. The structural variation of the N-terminal truncated apoE3 and
      apoE4 protein provides useful information that helps to explain the greater
      aggregation of the apoE4 isoform and thus has implication for the involvement of
      apoE4 in AD.

PMID- 15475581
TI  - High frequency dynamics in hemoglobin measured by magnetic relaxation dispersion.
AB  - The magnetic relaxation dispersion profiles for formate, acetate, and water
      protons are reported for aqueous solutions of hemoglobin singly and doubly
      labeled with a nitroxide and mercury(II) ion at cysteines at beta-93. Using two
      spin labels, one nuclear and one electron spin, a long intramolecular vector is
      defined between the two beta-93 positions in the protein. The paramagnetic
      contributions to the observed 1H spin-lattice relaxation rate constant are
      isolated from the magnetic relaxation dispersion profiles obtained on a dual
      magnet apparatus that provides spectral density functions characterizing
      fluctuations sensed by intermoment dipolar interactions in the time range from
      the tens of microseconds to approximately 1 ps. Both formate and acetate ions are
      found to bind specifically within 5 angstroms of the beta-93 spin-label position
      and the relaxation dispersion has inflection points corresponding to correlation
      times of 30 ps and 4 ns for both ions. The 4-ns motion is identified with
      exchange of the anions from the site, whereas the 30-ps correlation time is
      identified with relative motions of the spin label and the bound anion in the
      protein environment close to beta-93. The magnetic field dependence of the
      paramagnetic contributions in both cases is well described by a simple Lorentzian
      spectral density function; no peaks in the spectral density function are
      observed. Therefore, the high frequency motions of the protein monitored by the
      intramolecular vector defined by the electron and nuclear spin are well
      characterized by a stationary random function of time. Attempts to examine long
      vector fluctuations by employing electron spin and nuclear spin double-labeling
      techniques did not yield unambiguous characterization of the high frequency
      motions of the vector between beta-93 positions on different chains.

PMID- 15475582
TI  - Plasticity of influenza haemagglutinin fusion peptides and their interaction with
      lipid bilayers.
AB  - A detailed molecular dynamics study of the haemagglutinin fusion peptide (N
      terminal 20 residues of the HA2 subunits) in a model bilayer has yielded useful
      information about the molecular interactions leading to insertion into the
      lipids. Simulations were performed on the native sequence, as well as a number of
      mutant sequences, which are either fusogenic or nonfusogenic. For the native
      sequence and fusogenic mutants, the N-terminal 11 residues of the fusion peptides
      are helical and insert with a tilt angle of approximately 30 degrees with respect
      to the membrane normal, in very good agreement with experimental data. The tilted
      insertion of the native sequence peptide leads to membrane bilayer thinning and
      the calculated order parameters show larger disorder of the alkyl chains. These
      results indicate that the lipid packing is perturbed by the fusion peptide and
      could be used to explain membrane fusion. For the nonfusogenic sequences
      investigated, it was found that most of them equilibrate parallel to the
      interface plane and do not adopt a tilted conformation. The presence of a charged
      residue at the beginning of the sequence (G1E mutant) resulted in a more
      difficult case, and the outcomes do not fall straightforwardly into the general
      picture. Sequence searches have revealed similarities of the fusion peptide of
      influenza haemagglutinin with peptide sequences such as segments of porin,
      amyloid alpha eta peptide, and a peptide from the prion sequence. These results
      confirm that the sequence can adopt different folds in different environments.
      The plasticity and the conformational dependence on the local environment could
      be used to better understand the function of fusion peptides.

PMID- 15475583
TI  - A rapid fluorescence assay for FtsZ assembly indicates cooperative assembly with
      a dimer nucleus.
AB  - FtsZ is the major cytoskeletal protein operating in bacterial cell division. FtsZ
      assembles into protofilaments in vitro, and there has been some controversy over
      whether the assembly is isodesmic or cooperative. Assembly has been assayed
      previously by sedimentation and light scattering. However, these techniques will
      under-report small polymers. We have now produced a mutant of Escherichia coli
      FtsZ, L68W, which gives a 250% increase in tryptophan fluorescence upon
      polymerization. This provides a real-time assay of polymer that is directly
      proportional to the concentration of subunit interfaces. FtsZ-L68W is functional
      for cell division, and should therefore be a valid model for studying the
      thermodynamics and kinetics of FtsZ assembly. We assayed assembly at pH 7.7 and
      pH 6.5, in 2.5 mM EDTA. EDTA blocks GTP hydrolysis and should give an assembly
      reaction that is not complicated by the irreversible hydrolysis step. Assembly
      kinetics was determined with a stopped-flow device for a range of FtsZ
      concentrations. When assembly was initiated by adding 0.2 mM GTP, fluorescence
      increase showed a lag, followed by nucleation, elongation, and a plateau. The
      assembly curves were fit to a cooperative mechanism that included a monomer
      activation step, a weak dimer nucleus, and elongation. Fragmentation was absent
      in the model, another characteristic of cooperative assembly. We are left with an
      enigma: how can the FtsZ protofilament, which appears to be one-subunit thick,
      assemble with apparent cooperativity?

PMID- 15475584
TI  - Lateral diffusion of PEG-Lipid in magnetically aligned bicelles measured using
      stimulated echo pulsed field gradient 1H NMR.
AB  - Lateral diffusion measurements of PEG-lipid incorporated into magnetically
      aligned bicelles are demonstrated using stimulated echo (STE) pulsed field
      gradient (PFG) proton (1H) nuclear magnetic resonance (NMR) spectroscopy.
      Bicelles were composed of dimyristoyl phosphatidylcholine (DMPC) plus dihexanoyl
      phosphatidylcholine (DHPC) (q = DMPC/DHPC molar ratio = 4.5) plus 1 mol %
      (relative to DMPC) dimyristoyl phosphatidylethanolamine-N-[methoxy(polyethylene
      glycol)-2000] (DMPE-PEG 2000) at 25 wt % lipid. 1H NMR STE spectra of
      perpendicular aligned bicelles contained only resonances assigned to residual HDO
      and to overlapping contributions from a DMPE-PEG 2000 ethoxy headgroup plus DHPC
      choline methyl protons. Decay of the latter's STE intensity in the STE PFG 1H NMR
      experiment (g(z) = 244 G cm(-1)) yielded a DMPE-PEG 2000 (1 mol %, 35 degrees C)
      lateral diffusion coefficient D = 1.35 x 10(-11) m2 s(-1). Hence, below the
      "mushroom-to-brush" transition, DMPE-PEG 2000 lateral diffusion is dictated by
      its DMPE hydrophobic anchor. D was independent of the diffusion time, indicating
      unrestricted lateral diffusion over root mean-square diffusion distances of
      microns, supporting the "perforated lamellae" model of bicelle structure under
      these conditions. Overall, the results demonstrate the feasibility of lateral
      diffusion measurements in magnetically aligned bicelles using the STE PFG NMR
      technique.

PMID- 15475585
TI  - Modeling the effect of deregulated proliferation and apoptosis on the growth
      dynamics of epithelial cell populations in vitro.
AB  - We present a three-dimensional individual cell-based, biophysical model to study
      the effect of normal and malfunctioning growth regulation and control on the
      spatial-temporal organization of growing cell populations in vitro. The model
      includes explicit representations of typical epithelial cell growth regulation
      and control mechanisms, namely 1), a cell-cell contact-mediated form of growth
      inhibition; 2), a cell-substrate contact-dependent cell-cycle arrest; and 3), a
      cell-substrate contact-dependent programmed cell death (anoikis). The model cells
      are characterized by experimentally accessible biomechanical and cell-biological
      parameters. First, we study by variation of these cell-specific parameters which
      of them affect the macroscopic morphology and growth kinetics of a cell
      population within the initial expanding phase. Second, we apply selective
      knockouts of growth regulation and control mechanisms to investigate how the
      different mechanisms collectively act together. Thereby our simulation studies
      cover the growth behavior of epithelial cell populations ranging from
      undifferentiated stem cell populations via transformed variants up to tumor cell
      lines in vitro. We find that the cell-specific parameters, and in particular the
      strength of the cell-substrate anchorage, have a significant impact on the
      population morphology. Furthermore, they control the efficacy of the growth
      regulation and control mechanisms, and consequently tune the transition from
      controlled to uncontrolled growth that is induced by the failures of these
      mechanisms. Interestingly, however, we find the qualitative and quantitative
      growth kinetics to be remarkably robust against variations of cell-specific
      parameters. We compare our simulation results with experimental findings on a
      number of epithelial and tumor cell populations and suggest in vitro experiments
      to test our model predictions.

PMID- 15475586
TI  - Structure and tropomyosin binding properties of the N-terminal capping domain of
      tropomodulin 1.
AB  - Two families of actin regulatory proteins are the tropomodulins and tropomyosins.
      Tropomodulin binds to tropomyosin (TM) and to the pointed end of actin filaments
      and "caps" the pointed end (i.e., inhibits its polymerization and
      depolymerization). Tropomodulin 1 has two distinct actin-capping regions: a
      folded C-terminal domain (residues 160-359), which does not bind to TM, and a
      conserved, N-terminal region, within residues 1-92 that binds TM and requires TM
      for capping activity. NMR and circular dichroism were used to determine the
      structure of a peptide containing residues 1-92 of tropomodulin (Tmod1(1-92)) and
      to define its TM binding site. Tmod1(1-92) is mainly disordered with only one
      helical region, residues 24-35. This helix forms part of the TM binding domain,
      residues 1-35, which become more ordered upon binding a peptide containing the N
      terminus of an alpha-TM. Mutation of L27 to E or G in the Tmod helix reduces TM
      affinity. Residues 49-92 are required for capping but do not bind TM. Of these,
      residues 67-75 have the sequence of an amphipathic helix, but are not helical.
      Residues 55-62 and 76-92 display negative 1H-15N heteronuclear Overhauser
      enhancements showing they are flexible. The conformational dynamics of these
      residues may be important for actin capping activity.

PMID- 15475587
TI  - Flash-induced oxygen evolution in photosynthesis: simple solution for the
      extended S-state model that includes misses, double-hits, inactivation, and
      backward-transitions.
AB  - Flash-induced oxygen evolution in higher plants, algae, and cyanobacteria
      exhibits damped period-four oscillations. To explain such oscillations, Kok
      suggested a simple phenomenological S-state model, in which damping is due to
      empirical misses and double-hits. Here we developed an analytical solution for
      the extended Kok model that includes misses, double-hits, inactivation, and
      backward-transitions. The solution of the classic Kok model (with misses and
      double-hits only) can be obtained as a particular case of this solution. Simple
      equations describing the flash-number dependence of individual S-states and
      oxygen evolution in both cases are almost identical and, therefore, the classic
      Kok model does not have a significant advantage in its simplicity over the
      extended version considered in this article. Developed equations significantly
      simplify the fitting of experimental data via standard nonlinear regression
      analysis and make unnecessary the use of many previously developed methods for
      finding parameters of the model. The extended Kok model considered here can
      provide additional insight into the effect of dark relaxation between flashes and
      inactivation.

PMID- 15475588
TI  - Miscibility of ternary mixtures of phospholipids and cholesterol in monolayers,
      and application to bilayer systems.
AB  - We investigate miscibility transitions of two different ternary lipid mixtures,
      DOPC/DPPC/Chol and POPC/PSM/Chol. In vesicles, both of these mixtures of an
      unsaturated lipid, a saturated lipid, and cholesterol form micron-scale domains
      of immiscible liquid phases for only a limited range of compositions. In
      contrast, in monolayers, both of these mixtures produce two distinct regions of
      immiscible liquid phases that span all compositions studied, the alpha-region at
      low cholesterol and the beta-region at high cholesterol. In other words, we find
      only limited overlap in miscibility phase behavior of monolayers and bilayers for
      the lipids studied. For vesicles at 25 degrees C, the miscibility phase boundary
      spans portions of both the monolayer alpha-region and beta-region. Within the
      monolayer beta-region, domains persist to high pressures, yet within the alpha
      region, miscibility phase transition pressures always fall below 15 mN/m, far
      below the bilayer equivalent pressure of 32 mN/m. Approximately equivalent phase
      behavior is observed for monolayers of DOPC/DPPC/Chol and for monolayers of
      POPC/PSM/Chol. As expected, pressure-area isotherms of our ternary lipid mixtures
      yield smaller molecular area and compressibility for monolayers containing more
      saturated acyl chains and cholesterol. All monolayer experiments were conducted
      under argon. We show that exposure of unsaturated lipids to air causes monolayer
      surface pressures to decrease rapidly and miscibility transition pressures to
      increase rapidly.

PMID- 15475589
TI  - Double tether extraction from human neutrophils and its comparison with CD4+ T
      lymphocytes.
AB  - The initial arrest and subsequent rolling of a leukocyte on the vascular
      endothelium is believed to be facilitated by the extraction of tethers, which are
      narrow membranous tubes drawn from the leukocyte. Although single tether
      extraction from neutrophils has been studied thoroughly, the relationship between
      the tether force (F) and tether-growth velocity (U(t)) is still unknown for
      double tethers drawn from neutrophils. In this study, we have determined this
      relationship with the micropipette-aspiration technique. As a comparison, tether
      extraction from CD4+ T-lymphocytes was also studied. The threshold force and
      effective viscosity for single tether extraction from passive CD4+ T-lymphocytes
      were found to be 46 pN and 1.55 pN x s/microm, respectively. These values were
      modulated by stimulation with phorbol myristate acetate (PMA), but not
      interleukin-8 (IL-8). More importantly, for both types of leukocyte, the
      threshold force and effective viscosity for double tether extraction are about
      twice as large as those corresponding to single tether extraction. Neither IL-8
      nor PMA stimulation had any effect on this correlation. These results indicate
      that double tethers are highly localized on cellular surfaces and independent of
      each other during the rolling process.

PMID- 15475590
TI  - Kinetics of intracellular ice formation in one-dimensional arrays of interacting
      biological cells.
AB  - Although cell-cell interactions are known to significantly affect the kinetics of
      intracellular ice formation (IIF) during tissue freezing, this effect is not well
      understood. Progress in elucidating the mechanism and role of intercellular ice
      propagation in tissue freezing has been hampered in part by limitations in
      experimental design and data analysis. Thus, using rapid-cooling cryomicroscopy,
      IIF was measured in adherent cells cultured in micropatterned linear constructs
      (to control cell-cell interactions and minimize confounding factors). By fitting
      a Markov chain model to IIF data from micropatterned HepG2 cell pairs, the
      nondimensional rate of intercellular ice propagation was found to be alpha = 10.4
      +/- 0.1. Using this measurement, a new generator matrix was derived to predict
      the kinetics of IIF in linear four-cell constructs; cryomicroscopic measurements
      of IIF state probabilities in micropatterned four-cell arrays conformed with
      theoretical predictions (p < 0.05), validating the modeling assumptions. Thus,
      the theoretical model was extended to allow prediction of IIF in larger tissues,
      using Monte Carlo techniques. Simulations were performed to investigate the
      effects of tissue size and ice propagation rate, for one-dimensional tissue
      constructs containing up to 100 cells and nondimensional propagation rates in the
      range 0.1 < or = alpha < or = 1000.

PMID- 15475591
TI  - Identification of quenchers of photoexcited States as novel agents for skin
      photoprotection.
AB  - Photooxidative stress is a key mechanism in UVA-induced skin photodamage.
      Photoexcited states of endogenous UVA chromophores such as porphyrins, melanin
      precursors, and cross-link-fluorophores of skin collagen exert skin photodamage
      by direct reaction with substrate molecules (type I photosensitization) or
      molecular oxygen (type II), leading to formation of reactive oxygen species.
      Based on our previous research on the role of photoexcited states of endogenous
      skin chromophores as sensitizers of photooxidative stress, we describe here the
      identification of a novel class of chemopreventive agents for topical skin
      photoprotection: quenchers of photoexcited states (QPES). QPES compounds
      antagonize the harmful excited state chemistry of endogenous sensitizers by
      physical quenching, facilitating the harmless return of the sensitizer excited
      state to the electronic ground state by energy dissipation. To identify QPES
      compounds suitable for development, we designed a primary screening assay based
      on QPES suppression of photosensitized plasmid cleavage using conditions that
      exclude antioxidants. This screen is followed with a screen to test for
      nonsacrificial quenching of dye-sensitized singlet oxygen ((1)O(2)) formation by
      electron paramagnetic resonance detection of 2,2,6,6-tetramethyl-piperidine-1
      oxyl, a stable free radical indicative of (1)O(2) formation. These initial
      screens identified a pyrrolidine pharmacophore with pronounced QPES activity, and
      l-proline and other noncytotoxic proline derivatives containing this
      pharmacophore were then screened for efficacy in cellular models of sensitized
      photodamage. These compounds showed QPES protection against dye-sensitized and
      psoralen-UVA-induced apoptosis and suppression of proliferation in cultured human
      skin keratinocytes and fibroblasts. Furthermore, QPES photoprotection of
      reconstructed full thickness human skin exposed to solar simulated light has been
      demonstrated.

PMID- 15475592
TI  - GI262570, a peroxisome proliferator-activated receptor {gamma} agonist, changes
      electrolytes and water reabsorption from the distal nephron in rats.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists have been
      shown to have significant therapeutic benefits such as desirable glycemic control
      in type 2 diabetic patients; however, these agents may cause fluid retention in
      susceptible individuals. Since PPARgamma is expressed selectively in distal
      nephron epithelium, we studied the mechanism of PPARgamma agonist-induced fluid
      retention using male Sprague-Dawley rats treated with either vehicle or GI262570
      (farglitazar), a potent PPARgamma agonist. GI262570 (20 mg/kg/day) induced a
      plasma volume expansion. The plasma volume expansion was accompanied by a small
      but significant decrease in plasma potassium concentration. Small but significant
      increases in plasma sodium and chloride concentrations were also observed. These
      changes in serum electrolytes suggested an activation of the renal
      mineralocorticoid response system; however, GI262570-treated rats had lower
      plasma levels of aldosterone compared with vehicle-treated controls. mRNA levels
      for a group of genes involved in distal nephron sodium and water absorption are
      changed in the kidney medulla with GI262570 treatment. In addition, due to a
      possible rebound effect on epithelial sodium channel (ENaC) activity, a low dose
      of amiloride did not prevent GI262570-induced fluid retention. On the contrary,
      the rebound effect after amiloride treatment potentiated GI262570-induced plasma
      volume expansion. This is at least partially due to a synergistic effect of
      GI262570 and the rebound from amiloride treatment on ENaCalpha expression. In
      summary, our current data suggest that GI262570 can increase water and sodium
      reabsorption in distal nephron by stimulating the ENaC and Na,K-ATPase system.
      This may be an important mechanism for PPARgamma agonist-induced fluid retention.

PMID- 15475593
TI  - Kinin peptides in human trapezius muscle during sustained isometric contraction
      and their relation to pain.
AB  - To determine the muscular concentration of bradykinin and kallidin during static
      contraction, microdialysis probes were implanted bilaterally in the trapezius
      muscles of healthy women. Three hours after probe implantation, 200 microM of the
      angiotensin-converting enzyme (ACE) inhibitor enalaprilat were added to the
      perfusion solution in one of the sides for 30 min. Thirty minutes later, the
      subjects performed a sustained bilateral shoulder abduction at 10% of the maximal
      voluntary contraction until exhaustion. This protocol was repeated twice, with an
      interval of at least 17 days. High intersession repeatability was observed in the
      concentration of bradykinin but not of kallidin. Enalaprilat induced a
      significant increase in bradykinin levels in the dialysate, without affecting
      kallidin levels. The sustained contraction induced a significant increase in
      dialysate levels of both kinin peptides. The contraction also induced a
      significant increase in pain ratings, as measured by a visual analog scale.
      During contraction, positive correlations were found between pain ratings and
      levels of kinin peptides in dialysate, predominantly in the side previously
      perfused with enalaprilat. Subjects with the higher pain ratings also showed
      larger increases in kinin peptides in the side previously perfused with
      enalaprilat. The present results show that both plasma and tissue kinin
      kallikrein are activated during muscle contraction, but that their metabolic
      pathways are differently regulated during rest and contraction, because they
      showed a different response to ACE inhibition. They also indicate that
      intramuscular kinin peptides levels, and ACE activity, may contribute to muscle
      pain.

PMID- 15475594
TI  - Effects of bilateral vestibular nucleus lesions on cardiovascular regulation in
      conscious cats.
AB  - The vestibular system participates in cardiovascular regulation during postural
      changes. In prior studies (Holmes MJ, Cotter LA, Arendt HE, Cas SP, and Yates BJ.
      Brain Res 938: 62-72, 2002, and Jian BJ, Cotter LA, Emanuel BA, Cass SP, and
      Yates BJ. J Appl Physiol 86: 1552-1560, 1999), transection of the vestibular
      nerves resulted in instability in blood pressure during nose-up body tilts,
      particularly when no visual information reflecting body position in space was
      available. However, recovery of orthostatic tolerance occurred within 1 wk,
      presumably because the vestibular nuclei integrate a variety of sensory inputs
      reflecting body location. The present study tested the hypothesis that lesions of
      the vestibular nuclei result in persistent cardiovascular deficits during
      orthostatic challenges. Blood pressure and heart rate were monitored in five
      conscious cats during nose-up tilts of varying amplitude, both before and after
      chemical lesions of the vestibular nuclei. Before lesions, blood pressure
      remained relatively stable during tilts. In all animals, the blood pressure
      responses to nose-up tilts were altered by damage to the medial and inferior
      vestibular nuclei; these effects were noted both when animals were tested in the
      presence and absence of visual feedback. In four of the five animals, the lesions
      also resulted in augmented heart rate increases from baseline values during 60
      degrees nose-up tilts. These effects persisted for longer than 1 wk, but they
      gradually resolved over time, except in the animal with the worst deficits. These
      observations suggest that recovery of compensatory cardiovascular responses after
      loss of vestibular inputs is accomplished at least in part through plastic
      changes in the vestibular nuclei and the enhancement of the ability of vestibular
      nucleus neurons to discriminate body position in space by employing
      nonlabyrinthine signals.

PMID- 15475595
TI  - Echocardiographic parameters discriminating myocardial infarction with pulmonary
      congestion from myocardial infarction without congestion in the mouse.
AB  - Our aim was to establish parameters describing systolic and diastolic function in
      mice after myocardial infarction (MI) that distinguish MI with pulmonary
      congestion from MI without congestion. Echocardiography, left ventricular (LV)
      catheterization, and infarct size measurements were performed on days 3, 5, 7,
      and 14 after ligation of the left coronary artery in C57BL/6 mice. Sham-operated
      mice were used as controls (Sham). MI mice with lung weight normalized to tibial
      length >125% of the average in the corresponding Sham group were considered to
      have pulmonary congestion (MIchf). MI mice with a smaller increase were called MI
      nonfailing (MInf). An infarct >40% of total LV circumference measured in two
      dimensional long axis distinguished MIchf from MInf on both an average and an
      individual basis. Mean maximum rate of rise of LV pressure, LV fractional
      shortening, and posterior wall shortening velocity were significantly lower in
      MIchf compared with Sham at all time points and to MInf at 7 days. The diastolic
      parameters mitral flow deceleration velocity, LV end-diastolic pressure, and
      maximum rate of decline in LV pressure (LVdP/dtmin) discriminated the MIchf
      groups from Sham at all time points. Mitral flow deceleration velocity and
      LVdP/dtmin separated MIchf from MInf at 7 days. In addition to distinguishing all
      the groups on an average basis, left atrial diameter distinguished all MIchf
      animals from Sham and MInf. In conclusion, significantly increased left atrial
      diameter and infarct size >40% of total LV circumference may serve as major
      criteria for heart failure with pulmonary congestion after MI in mice.

PMID- 15475596
TI  - C57BL/6J and B6.V-LEPOB mice differ in the cholinergic modulation of sleep and
      breathing.
AB  - Respiratory and arousal state control are heritable traits in mice. B6.V-Lep(ob)
      (ob) mice are leptin deficient and differ from C57BL/6J (B6) mice by a variation
      in the gene coding for leptin. The ob mouse has morbid obesity and disordered
      breathing that is homologous to breathing of obese humans. This study tested the
      hypothesis that microinjecting neostigmine into the pontine reticular nucleus,
      oral part (PnO), of B6 and ob mice alters sleep and breathing. In B6 and ob mice,
      neostigmine caused a concentration-dependent increase (P < 0.0001) in percentage
      of time spent in a rapid eye movement (REM) sleeplike state (REM-Neo). Relative
      to saline (control), higher concentrations of neostigmine increased REM-Neo
      duration and the number of REM-Neo episodes in B6 and ob mice and decreased
      percent wake, percent non-REM, and latency to onset of REM-Neo (P < 0.001). In B6
      and ob mice, REM sleep enhancement by neostigmine was blocked by atropine.
      Differences in control amounts of sleep and wakefulness between B6 and the
      congenic ob mice also were identified. After PnO injection of saline, ob mice
      spent significantly (P < 0.05) more time awake and less time in non-REM sleep. B6
      mice displayed more (P < 0.01) baseline locomotor activity than ob mice, and PnO
      neostigmine decreased locomotion (P < 0.0001) in B6 and ob mice. Whole body
      plethysmography showed that PnO neostigmine depressed breathing (P < 0.001) in B6
      and ob mice and caused greater respiratory depression in B6 than ob mice (P <
      0.05). Western blot analysis identified greater (P < 0.05) expression of M2
      muscarinic receptor protein in ob than B6 mice for cortex, midbrain, cerebellum,
      and pons, but not medulla. Considered together, these data provide the first
      evidence that pontine cholinergic control of sleep and breathing varies between
      mice known to differ by a spontaneous mutation in the gene coding for leptin.

PMID- 15475597
TI  - Redistribution of intestinal microcirculatory oxygenation during acute
      hemodilution in pigs.
AB  - Acute normovolemic hemodilution (ANH) compromizes intestinal microcirculatory
      oxygenation; however, the underlying mechanisms are incompletely understood. We
      hypothesized that contributors herein include redistribution of oxygen away from
      the intestines and shunting of oxygen within the intestines. The latter may be
      due to the impaired ability of erythrocytes to off-load oxygen within the
      microcirculation, thus yielding low tissue/plasma Po(2) but elevated
      microcirculatory hemoglobin oxygen (HbO(2)) saturations. Alternatively, oxygen
      shunting may also be due to reduced erythrocyte deformability, hindering the
      ability of erythrocytes to enter capillaries. Anesthetized pigs underwent ANH
      (20, 40, 60, and 90 ml/kg hydroxyethyl starch; ANH group: n = 10; controls: n =
      5). We measured systemic and mesenteric perfusion. Microvascular intestinal
      oxygenation was measured independently by remission spectrophotometry
      [microcirculatory HbO(2) saturation (muHbO(2))] and palladium-porphyrin
      phosphorescence quenching [microcirculatory oxygen pressure in plasma/tissue
      (muPo(2))]. Microcirculatory oxygen shunting was assessed as the disparity
      between mucosal and mesenteric venous HbO(2) saturation (HbO(2)-gap). Erythrocyte
      deformability was measured as shear stress-induced cell elongation (LORCA
      difractometer). ANH reduced hemoglobin concentration from 8.1 to 2.2 g/dl.
      Relative mesenteric perfusion decreased (decreased mesenteric/systemic perfusion
      fraction). A paralleled reduction occurred in mucosal muHbO(2) (68 +/- 2 to 41 +/
      3%) and muPo(2) (28 +/- 1 to 17 +/- 1 Torr). Thus the proposed constellation
      indicative for oxygen off-load deficits (sustained muHbO(2) at decreased muPo(2))
      did not develop. A twofold increase in the HbO(2)-gap indicated increasing
      intestinal microcirculatory oxygen shunting. Significant impairment in
      erythrocyte deformability developed during ANH. We conclude that reduced
      intestinal oxygenation during ANH is, in addition to redistribution of oxygen
      delivery away from the intestines, associated with oxygen shunting within the
      intestines. This shunting appears to be not primarily caused by oxygen off-load
      deficit but rather by oxygen/erythrocytes bypassing capillaries, wherein a
      potential contributor is impaired erythrocyte deformability.

PMID- 15475598
TI  - Egr-1 antisense oligonucleotides inhibit hypoxia-induced proliferation of
      pulmonary artery adventitial fibroblasts.
AB  - In most mammalian species, chronic exposure to hypoxia leads to pulmonary
      hypertension and vascular remodeling. The adventitial fibroblast, because of its
      ability to proliferate in response to hypoxia, is thought to be a critical cell
      in the remodeling process. However, the transcription factors driving hypoxia
      induced fibroblast proliferation have yet to be elucidated. The early growth
      response-1 (Egr-1) transcription factor has been shown to be upregulated by
      hypoxia in pulmonary artery adventitial fibroblasts. We therefore hypothesized
      that Egr-1 is directly involved in hypoxia-induced adventitial fibroblast
      proliferation. Immunohistochemical analysis of in vivo lung tissue from animals
      exposed to chronic hypoxia revealed increased expression of Egr-1 in the
      pulmonary artery fibroblasts vs. expression shown in normoxic controls. In
      fibroblasts cultured from chronically hypoxic animals, exposure to 1% oxygen
      upregulated Egr-1 protein and cell proliferation. To evaluate the role of Egr-1
      in hypoxia-induced proliferation, we employed an Egr-1 antisense strategy.
      Addition of antisense Egr-1 oligonucleotides, but not sense oligonucleotides,
      attenuated the hypoxia-induced upregulation of Egr-1 protein and reduced hypoxia
      induced DNA synthesis by 50%. Cell proliferation was also significantly inhibited
      by the addition of antisense Egr-1 oligonucleotides but not the sense
      oligonucleotides. In addition, hypoxia-induced upregulations of cyclin D and
      epidermal growth factor receptor were attenuated by Egr-1 antisense
      oligonucleotides. We conclude that Egr-1 protein expression is very sensitive to
      upregulation by hypoxia in pulmonary artery adventitial fibroblasts and that it
      plays an important role in the autonomous growth phenotype induced by hypoxia in
      these cells.

PMID- 15475599
TI  - Attenuation of induced bronchoconstriction in healthy subjects: effects of
      breathing depth.
AB  - The effects of breathing depth in attenuating induced bronchoconstriction were
      studied in 12 healthy subjects. On four separate, randomized occasions, the depth
      of a series of five breaths taken soon (approximately 1 min) after methacholine
      (MCh) inhalation was varied from spontaneous tidal volume to lung volumes
      terminating at approximately 80, approximately 90, and 100% of total lung
      capacity (TLC). Partial forced expiratory flow at 40% of control forced vital
      capacity (V(part)) and residual volume (RV) were measured at control and again at
      2, 7, and 11 min after MCh. The decrease in V(part) and the increase in RV were
      significantly less when the depth of the five-breath series was progressively
      increased (P < 0.001), with a linear relationship. The attenuating effects of
      deep breaths of any amplitude were significantly greater on RV than V(part) (P <
      0.01) and lasted as long as 11 min, despite a slight decrease with time when the
      end-inspiratory lung volume was 100% of TLC. In conclusion, in healthy subjects
      exposed to MCh, a series of breaths of different depth up to TLC caused a
      progressive and sustained attenuation of bronchoconstriction. The effects of the
      depth of the five-breath series were more evident on the RV than on V(part),
      likely due to the different mechanisms that regulate airway closure and
      expiratory flow limitation.

PMID- 15475600
TI  - Hematological and acid-base changes in men during prolonged exercise with and
      without sodium-lactate infusion.
AB  - An emerging technique used for the study of metabolic regulation is the elevation
      of lactate concentration with a sodium-lactate infusion, the lactate clamp (LC).
      However, hematological and acid-base properties affected by the infusion of
      hypertonic solutions containing the osmotically active strong ions sodium (Na(+))
      and lactate (Lac(-)) are a concern for clinical and research applications of LC.
      In the present study, we characterized the hematological and plasma acid-base
      changes during rest and prolonged, light- to moderate-intensity (55% Vo(2 peak))
      exercise with and without LC. During the control (Con) trial, subjects were
      administered an isotonic, isovolumetric saline infusion. During LC, plasma
      lactate concentration ([Lac(-)]) was elevated to 4 meq/l during rest and to 4-7
      meq/l during exercise. During LC at rest, there were rapid and transient changes
      in plasma, erythrocyte, and blood volumes. LC resulted in decreased plasma [H(+)]
      (from 39.6 to 29.6 neq/l) at the end of exercise while plasma [HCO(3)(-)]
      increased from 26 to 32.9 meq/l. Increased plasma strong ion difference [SID],
      due to increased [Na(+)], was the primary contributor to decreased [H(+)] and
      increased [HCO(3)(-)]. A decrease in plasma total weak acid concentration also
      contributed to these changes, whereas Pco(2) contributed little. The infusion of
      hypertonic LC caused only minor volume, acid-base, and CO(2) storage responses.
      We conclude that an LC infusion is appropriate for studies of metabolic
      regulation.

PMID- 15475601
TI  - Hemodynamic effects of leg crossing and skeletal muscle tensing during free
      standing in patients with vasovagal syncope.
AB  - Physical maneuvers can be applied to abort or delay an impending vasovagal faint.
      These countermaneuvers would be more beneficial if applied as a preventive
      measure. We hypothesized that, in patients with recurrent vasovagal syncope, leg
      crossing produces a rise in cardiac output (CO) and thereby in blood pressure
      (BP) with an additional rise in BP by muscle tensing. We analyzed the age and
      gender effect on the BP response. To confirm that, during the maneuvers,
      Modelflow CO changes in proportion to actual CO, 10 healthy subjects performed
      the study protocol with CO evaluated simultaneously by Modelflow and by inert gas
      rebreathing. Changes in Modelflow CO were similar in direction and magnitude to
      inert gas rebreathing-determined CO changes. Eighty-eight patients diagnosed with
      vasovagal syncope applied leg crossing after a 5-min free-standing period. Fifty
      four of these patients also applied tensing of leg and abdominal muscles. Leg
      crossing produced a significant rise in CO (+9.5%; P < 0.01) and thereby in mean
      arterial pressure (+3.3%; P < 0.01). Muscle tensing produced an additional
      increase in CO (+8.3%; P < 0.01) and mean arterial pressure (+7.8%; P < 0.01).
      The rise in BP during leg crossing was larger in the elderly.

PMID- 15475602
TI  - Twitch potentiation is greater after a fatiguing submaximal isometric contraction
      performed at short vs. long quadriceps muscle length.
AB  - Endurance time of a submaximal sustained contraction is longer when the muscle is
      fatigued in a shortened position. The aim of the present study was to compare
      central and peripheral mechanisms of fatigue after an isometric contraction of
      the knee extensor muscles performed at 20% maximal voluntary contraction (MVC) at
      two knee angles (35 degrees , short length vs. 75 degrees , long length; 0
      degrees = full extension) until exhaustion. Eleven men (24 +/- 4 yr) attended two
      experimental randomized sessions. Endurance time was greater at 35 degrees
      compared with 75 degrees (974 +/- 457 vs. 398 +/- 144 s; P < 0.001) despite a
      similar reduction in knee extensor MVC (-28.4 +/- 16.0%, P < 0.001 vs. -27.6 +/-
      18.8%, P < 0.001, respectively). Voluntary activation level was similarly
      depressed after the fatiguing contraction performed at the two muscle lengths (
      19 +/- 16.7% at 35 degrees , P < 0.01 vs. -13.7 +/- 14.5% at 75 degrees , P <
      0.01). After the fatiguing contraction, peak twitch potentiation was observed
      only at the short length (+31.8 +/- 17.6% at 35 degrees , P < 0.01 vs. +6.4 +/-
      21.3% at 75 degrees , P > 0.05), whereas M-wave properties were similarly altered
      for the two angles. These results suggest that 1) central fatigue at task failure
      for a sustained isometric contraction was not dependent on the muscle length, and
      2) the longer endurance time of a sustained isometric contraction performed at a
      shortened length is related to potentiation. It is suggested that the greater
      endurance time of a sustained isometric contraction observed at 35 degrees is
      related to the occurrence of potentiation at this short length, because central
      fatigue is similar at task failure for both tasks.

PMID- 15475603
TI  - Impact of changes in inspired oxygen and carbon dioxide on respiratory
      instability in the lamb.
AB  - We examined the effect of hypoxia and hypercapnia administered during
      deliberately induced periodic breathing (PB) in seven lambs following
      posthyperventilation apnea. Based on our theoretical analysis, the sensitivity or
      loop gain (LG) of the respiratory control system of the lamb is directly
      proportional to the difference between alveolar PO2 and inspired PO2. This
      analysis indicates that during PB, when by necessity LG is >1, replacement of the
      inspired gas with one of reduced PO2 lowers LG; if we made inspired PO2
      approximate alveolar PO2, we predict that LG would be approximately zero and
      breathing would promptly stabilize. In six lambs, we switched the inspired gas
      from an inspiratory oxygen fraction of 0.4 to one of 0.12 during an epoch of PB;
      PB was immediately suppressed, supporting the view that the peripheral
      chemoreceptors play a pivotal role in the genesis and control of unstable
      breathing in the lamb. In the six lambs in which we administered hypercapnic gas
      during PB, breathing instability was also suppressed, but only after a
      considerable time lag, indicating the CO2 effect is likely to have been mediated
      through the central chemoreceptors. When we simulated both interventions in a
      published model of the adult respiratory controller, PB was immediately
      suppressed by CO2 inhalation and exacerbated by inhalation of hypoxic gas. These
      fundamentally different responses in lambs and adult humans demonstrate that PB
      has differing underlying mechanisms in the two species.

PMID- 15475605
TI  - Postural changes in lung volumes and respiratory resistance in subjects with
      obesity.
AB  - Reduced functional residual capacity (FRC) is consistently found in obese
      subjects. In 10 obese subjects (mean +/- SE age 49.0 +/- 6 yr, weight 128.4 +/- 8
      kg, body mass index 44 +/- 3 kg/m2) without respiratory disease, we examined 1)
      supine changes in total lung capacity (TLC) and subdivisions, 2) whether values
      of total respiratory resistance (Rrs) are appropriate for mid-tidal lung volume
      (MTLV), and 3) estimated resistance of the nasopharyngeal airway (Rnp) in both
      sitting and supine postures. The results were compared with those of 13 control
      subjects with body mass indexes of <27 kg/m2. Rrs at 6 Hz was measured by
      applying forced oscillation at the mouth (Rrs,mo) or the nose (Rrs,na); Rnp was
      estimated from the difference between sequential measurements of Rrs,mo and
      Rrs,na. All measurements were made when subjects were seated and when supine.
      Obese subjects when seated had a restrictive defect with low TLC and FRC-to-TLC
      ratio; when supine, TLC fell 80 ml and FRC fell only 70 ml compared with a mean
      supine fall of FRC of 730 ml in control subjects. Values of Rrs,mo and Rrs,na at
      resting MTLV in obese subjects were about twice those in control subjects in both
      postures. Relating total respiratory conductance (1/Rrs) to MTLV, the increase in
      Rrs,mo in obese subjects was only partly explained by their reduced MTLV. Rnp was
      increased in some obese subjects in both postures. Despite the increased
      extrapulmonary mass load in obese subjects, further falls in TLC and FRC when
      supine were negligible. Rrs,mo at isovolume was increased. Further studies are
      needed to examine the causes of reduced TLC and increases in Rrs,mo and sometimes
      in Rnp in obese subjects.

PMID- 15475604
TI  - Inflammatory, hemostatic, and clinical changes in a baboon experimental model for
      heatstroke.
AB  - The mortality and neurological morbidity in heatstroke have been attributed to
      the host's inflammatory and hemostatic responses to heat stress, suggesting that
      immunomodulation may improve outcome. We postulated that an experimental baboon
      model of heatstroke will reproduce human responses and clinical outcome to allow
      testing of new therapeutic strategies. Eight anesthetized juvenile baboons (Papio
      hamadryas) were subjected to heat stress in an incubator maintained at 44-47
      degrees C until rectal temperature attained 42.5 degrees C (moderate heatstroke;
      n = 4) or systolic arterial pressure fell to <90 mmHg (severe heatstroke; n = 4)
      and were allowed to recover at room temperature. Four sham-heated animals served
      as a control group. Rectal temperature at the end of heat stress was 42.5 +/- 0.0
      and 43.3 +/- 0.1 degrees C, respectively. All heat-stressed animals had systemic
      inflammation and activated coagulation, indicated by increased plasma IL-6,
      prothrombin time, activated partial thromboplastin time, and D-dimer levels, and
      decreased platelet count. Biochemical markers and/or histology evidenced cellular
      injury/dysfunction: plasma levels of thrombomodulin, creatinine, creatine kinase,
      lactic dehydrogenase, and alanine aminotransferase were increased, and varying
      degrees of tissue damage were present in liver, brain, and gut. No baboon with
      severe heatstroke survived. Neurological morbidity but no mortality was observed
      in baboons with moderate heatstroke. Nonsurvivors displayed significantly greater
      coagulopathy, inflammatory activity, and tissue injury than survivors. Sham
      heated animals had an uneventful course. Heat stress elicited distinct patterns
      of inflammatory and hemostatic responses associated with outcome. The baboon
      model of heatstroke appears suitable for testing whether immunomodulation of the
      host's responses can improve outcome.

PMID- 15475606
TI  - Rapid formation of functional muscle in vitro using fibrin gels.
AB  - The transition of a muscle cell from a differentiated myotube into an adult
      myofiber is largely unstudied. This is primarily due to the difficulty of
      isolating specific developmental stimuli in vivo and the inability to maintain
      viable myotubes in culture for sufficient lengths of time. To address these
      limitations, a novel method for rapidly generating three-dimensional engineered
      muscles using fibrin gel casting has been developed. Myoblasts were seeded and
      differentiated on top of a fibrin gel. Cell-mediated contraction of the gel
      around artificial anchors placed 12 mm apart culminates 10 days after plating in
      a tubular structure of small myotubes (10-microm diameter) surrounded by a fibrin
      gel matrix. These tissues can be connected to a force transducer and electrically
      stimulated between parallel platinum electrodes to monitor physiological
      function. Three weeks after plating, the three-dimensional engineered muscle
      generated a maximum twitch force of 329 +/- 26.3 microN and a maximal tetanic
      force of 805.8 +/- 55 microN. The engineered muscles demonstrated normal
      physiological function including length-tension and force-frequency
      relationships. Treatment with IGF-I resulted in a 50% increase in force
      production, demonstrating that these muscles responded to hormonal interventions.
      Although the force production was maximal at 3 wk, constructs can be maintained
      in culture for up to 6 wk with no intervention. We conclude that fibrin-based
      gels provide a novel method to engineer three-dimensional functional muscle
      tissue and that these tissues may be used to model the development of skeletal
      muscle in vitro.

PMID- 15475607
TI  - Physical exercise decreases neuronal activity in the posterior hypothalamic area
      of spontaneously hypertensive rats.
AB  - Recently, physical exercise has been shown to significantly alter neurochemistry
      and neuronal function and to increase neurogenesis in discrete brain regions.
      Although we have documented that physical exercise leads to molecular changes in
      the posterior hypothalamic area (PHA), the impact on neuronal activity is
      unknown. The purpose of the present study was to determine whether neuronal
      activity in the PHA is altered by physical exercise. Spontaneously hypertensive
      rats (SHR) were allowed free access to running wheels for a period of 10 wk
      (exercised group) or no wheel access at all (nonexercised group). Single-unit
      extracellular recordings were made in anesthetized in vivo whole animal
      preparations or in vitro brain slice preparations. The spontaneous firing rates
      of PHA neurons in exercised SHR in vivo were significantly lower (8.5 +/- 1.6 Hz,
      n = 31 neurons) compared with that of nonexercised SHR in vivo (13.7 +/- 1.8 Hz,
      n = 38 neurons; P < 0.05). In addition, PHA neurons that possessed a cardiac
      related rhythm in exercised SHR fired significantly lower (6.0 +/- 1.8 Hz, n = 11
      neurons) compared with nonexercised SHR (12.1 +/- 2.4 Hz, n = 18 neurons; P <
      0.05). Similarly, the spontaneous in vitro firing rates of PHA neurons from
      exercised SHR were significantly lower (3.5 +/- 0.3 Hz, n = 67 neurons) compared
      with those of nonexercised SHR (5.6 +/- 0.5 Hz, n = 58 neurons; P < 0.001). Both
      the in vivo and in vitro findings support the hypothesis that physical exercise
      can lower spontaneous activity of neurons in a cardiovascular regulatory region
      of the brain. Thus physical exercise may alter central neural control of
      cardiovascular function by inducing lasting changes in neuronal activity.

PMID- 15475608
TI  - Equilibrium analysis of allosteric interactions shows zero-order effects.
AB  - The binding of effector to an allosteric protein exhibits a non-Michaelis-Menten
      behavior, resulting in either ultrasensitive or subsensitive response. In the
      present work, a modular approach has been developed to determine the response
      curve for allosteric systems at higher concentration of allosteric enzyme than
      that of effector (zero-order sensitivity, as observed in enzyme cascades) by
      equilibrium analysis. The analysis shows that, in an allosteric system, the zero
      order effect can make the response ultrasensitive or subsensitive with respect to
      the enzyme concentration. The response is dependent on the number of binding
      sites, cooperativity, and the total effector concentration. The framework was
      further applied to a well studied allosteric protein, the Escherichia coli
      aspartate transcarbamoylase. The predictions are found to be consistent with the
      reported experimental data.

PMID- 15475609
TI  - Sharpening the scissors: mitochondrial fission with aid.
AB  - Over the past 5 yr, research in mitochondrial morphology has advanced rapidly,
      mainly as a result of the identification of protein factors involved in
      mitochondrial fission and fusion. The pathological relevance of these processes
      becomes clear as apoptotic cell death evidently involves mitochondrial fission
      and fusion machinery. Although the mechanisms by which cells maintain
      mitochondrial morphology are now beginning to be understood, interrelation
      between mitochondrial function and morphology is still not clear. This review
      describes the recent progress made in mitochondrial fission studies and ventures
      to seek an intricate link between morphology and function of mitochondria.

PMID- 15475610
TI  - Jak2 tyrosine kinase: a true jak of all trades?
AB  - Discovered roughly 10 yr ago, Jak2 tyrosine kinase has emerged as a critical
      molecule in mammalian development, physiology, and disease. Here, we review the
      early history of Jak2 and its role in health and disease. We will also review its
      critical role in mediating cytokine-dependent signal transduction. Additionally,
      more recent work demonstrating the importance of Jak2 in G protein-coupled
      receptor and tyrosine kinase growth factor receptor signal transduction will be
      discussed. The cellular and biochemical mechanisms by which Jak2 tyrosine kinase
      is activated and regulated within the cell also will be reviewed. Finally,
      structure-function and pharmacological-based studies that identified structural
      motifs and amino acids within Jak2 that are critical for its function will be
      examined. By reviewing the biology of Jak2 tyrosine kinase at the molecular,
      cellular, and physiological levels, we hope to advance the understanding of how a
      single gene can have such a profound impact on development, physiology, and
      disease.

PMID- 15475611
TI  - Ion channels and transporters involved in cell volume regulation and sensor
      mechanisms.
AB  - All animal cell types have an appropriate volume. Even under physiological
      conditions of constant extracellular osmolarity, cells must regulate their
      volume. Cell volume is subjected to alterations because of persistent
      physicochemical osmotic load resulting from Donnan-type colloid osmotic pressure
      and of cell activity-associated changes in intracellular osmolarity resulting
      from osmolyte transport and metabolism. The strategy adopted by animal cells for
      coping with volume regulation on osmotic perturbation is to activate transport
      pathways, including channels and transporters, mainly for inorganic osmolytes to
      drive water flow. Under normotonic conditions, cells undergo volume regulation by
      pump-mediated mechanisms. Under anisotonic conditions, volume regulation occurs
      by additional channel/transporter-mediated mechanisms. Cell volume regulation is
      also attained through adjustment of intracellular levels not only of inorganic
      but also of organic osmolytes with changing the expression of their transporters
      or regulation of metabolism. In cell volume regulation mechanism, several "volume
      sensors" are thought to be involved. A volume-sensitive Cl- channel has lately
      attracted considerable attention in this regard.

PMID- 15475612
TI  - The synaptic bouton acts like a salt shaker.
AB  - The physiological quantal responses at the neuromuscular junction and the bouton
      neuron show two classes based on amplitude such that the larger class is about 10
      times that of the smaller class; and, the larger class is composed of the smaller
      class. The ratio of the two classes changes with synaptogenesis, degeneration,
      nerve stimulation, and is readily altered with various challenges (ionic,
      tonicity, pharmacological agents). Statistical analyses demonstrate that each
      bouton or release site at the neruomuscular junction (NMJ) secretes a standard
      amount of transmitter (one quantum) with each action potential. The amount of
      transmitter secreted (quantal size) is frequency dependent. The quantal-vesicular
      exocytotic (QVE) hypothesis posits that the packet of secreted transmitter is
      released from one vesicle by exocytosis. The QVE hypothesis neither explains two
      quantal classes and subunits nor exocytosis of only one vesicle at each site. The
      latter observation requires a mechanism to select one vesicle from each array.
      Our porocytosis hypothesis states that the quantal packet is pulsed from an array
      of secretory pores. A salt shaker delivers a standard pinch of salt with each
      shake because salt flows through all openings in the cap. The variation in the
      pinch of salt or transmitter decreases with an increase in array size. The docked
      vesicles, paravesicular matrix, and porosomes (pores) of a release site form the
      secretory unit. In analogy with the sacromere as the functional unit of skeletal
      muscle, we term the array of docked vesicles and paravesicular grid along with
      the array of postsynaptic receptors a synaptomere. Pulsed secretion from an array
      explains the substructure of the postsynaptic response (quantum). The array
      guarantees a constant amount of secretion with each action potential and permits
      a given synapse to function in different responses because different frequencies
      would secrete signature amounts of transmitter. Our porocytosis hypothesis
      readily explains a change in quantal size during learning and memory with an
      increase in the number of elements (docked vesicles) composing the array.

PMID- 15475613
TI  - Messenger RNA decay in mammalian cells: the exonuclease perspective.
AB  - The majority of messenger RNA (mRNA) decay in mammalian cells appears to be the
      work of a series of RNA exoribonucleases. A set of multiple poly(A)-specific
      deadenylases has been identified, some, if not most, of which are likely to play
      a role in the key first step of mRNA turnover--the regulated shortening of the
      poly(A) tail. After deadenylation, the transcript likely gets degraded by either
      a 5'-to-3' or a 3'-to-5' exonucleolytic pathway. Interestingly, multiple
      exonucleases have been identified for both of these pathways that appear to form
      multicomponent complexes with diverse roles in cellular biology. Therefore these
      enzymes appear not only to be important components of the mRNA turnover
      machinery, but also may function in a networked fashion in the post
      transcriptional control of gene expression.

PMID- 15475614
TI  - The role of shear stress in atherosclerosis: action through gene expression and
      inflammation?
AB  - Atherosclerotic lesions preferentially localize near side branches or curved
      vessels. During the last few decades, research has been shown that low or low and
      oscillating shear stress is associated with plaque location. Despite ample
      evidence, the precise mechanism is unknown. This is mainly because of a lack of
      appropriate animal models. We describe two novel methods to study the hypothesis
      that shear stress acts through endothelial gene expression or shear stress acts
      through localizing of inflammation. Both literature evidence and own findings
      support a role for both mechanisms in atherosclerosis.

PMID- 15475615
TI  - EH proteins: multivalent regulators of endocytosis (and other pathways).
AB  - Endocytosis is a protein and lipid-trafficking pathway that occurs in all
      eukaryotic cells. It involves the internalization of plasma membrane proteins and
      lipids into the cell and the subsequent degradation of proteins in the lysosome
      or the recycling of proteins and lipids back to the plasma membrane. Over the
      past decade, studies in yeast and mammalian cells have revealed endocytosis to be
      a very complex molecular process that depends on regulated interactions between a
      variety of proteins and lipids. The Eps15 homology (EH) domain is a conserved,
      modular protein-interaction domain found in several endocytosis proteins. EH
      proteins can function as key regulators of endocytosis through their ability to
      interact with many of the other proteins involved in this process.

PMID- 15475616
TI  - Inflammation-induced "channelopathies" in the gastrointestinal smooth muscle.
AB  - Inflammation markedly alters the motility patterns of the gastrointestinal tract,
      resulting mostly in decreased excitability of smooth muscle. There is emerging
      evidence indicating that inflammation alters ion channel expression and function
      of smooth muscle cells. In this review we summarize studies defining the
      mechanisms affecting contractile and electrical activity of gastrointestinal
      smooth muscle. We have focused on the evidence for decreased calcium channel
      conductance and alterations in the intracellular signaling mechanisms and discuss
      the role of muscarinic receptor activation in models of gastrointestinal
      inflammation. We propose that some of the clinical symptoms of altered smooth
      muscle contraction in pathogenesis of gut disorders such as inflammatory bowel
      disease may be regulated at the level of the ion channel.

PMID- 15475617
TI  - Goiter prevalence, serum selenium, and urine iodine status in a previously iodine
      deficient area in Turkey.
AB  - This study was planned to investigate goiter prevalence and serum selenium and
      urine iodine status among school-age children in the Ankara region of Turkey.
      Nine hundred five (905) children were investigated; 847 of them were included in
      the study. Thyroid ultrasound was performed on children who were suspected of
      being goitrous at physical examination. Serum TSH, thyroxine, triiodotyronine,
      thyroid antibody, and urine iodine concentrations (UIC) are also measured.
      Ultrasound measurements revealed a goiter in 107 (12.6%) of the 847 children.
      Goiter prevalence was significantly lower among iodized-salt users compared to
      the noniodized salt using group. UIC and serum selenium levels in the goitrous
      group were significantly lower compared to the nongoitrous group. Despite legally
      enforced table salt iodization, the region shows the characteristics of mild
      iodine deficiency. In addition to lower UIC, goitrous children have lower serum
      selenium levels compared to the nongoitrous ones. Thus, selenium deficiency plays
      an important role in goiter endemics in Turkey. It can be postulated that table
      salt iodization might not be enough for the preventive measures of goiter, but
      informing people about the correct ways of iodized salt consumption, enforcing
      the iodization of industrial salts, and, as important as these measures, taking
      selenium deficiency into consideration are essential for preventing goiters in
      endemic areas.

PMID- 15475618
TI  - Mineral content of water and food in fluorotic villages and prevalence of dental
      fluorosis.
AB  - The fluoride (F), calcium (Ca), magnesium (Mg), zinc (Zn), copper (Cu), and
      phosphorus (P) content in potable water and food samples from endemic and
      nonendemic villages for fluorosis were analyzed. It was found that the F content
      in water was significantly higher (p<0.01) in endemic villages (4.20+/-1.6 ppm)
      than control villages (0.63+/-0.15 ppm), whereas the Ca, Cu, and Mg contents were
      found to be significantly lower (p<0.05) in endemic villages compared to control
      villages. However, there was no significant difference in Zn and P contents
      between the villages. Foods grown in endemic villages contained significantly
      higher (p<0.01) fluoride content as compared to control villages. There was no
      significant difference in Ca, Mg, P, and Zn contents in food grown in endemic and
      control villages. Copper content in cereals (p<0.05), pulses (p<0.01), and
      vegetables (p<0.01) in endemic villages was found significantly higher as
      compared to control villages. The overall prevalence of dental fluorosis in six
      endemic villages was 97.4% in boys and 96% in girls, which was significantly
      higher (p<0.01) than that of control villages, where it was 10.5% in boys and
      8.3% in girls. The prevalence of dental fluorosis was positively correlated
      (r=0.125, p<0.01) to fluoride and negatively correlated to Ca and Cu content in
      drinking water in endemic villages.

PMID- 15475619
TI  - Accumulation of calcium and phosphorus accompanied by inevitable accumulation of
      magnesium in human arteries.
AB  - To examine whether there were differences between races in regard to the
      relationships among element contents in the arteries, the authors investigated
      the relationships among the average contents of calcium, phosphorus, sulfur, and
      magnesium in the 18 kinds of the Thai artery. After ordinary dissection by
      medical students at Chiang Mai University was finished, the thoracic and
      abdominal aortas, ramifying site of the abdominal aorta into the common iliac
      arteries, coronary, common carotid, internal thoracic, subclavian, axillary,
      brachial, radial, superior and inferior mesenteric, renal, common iliac, internal
      iliac, and external iliac arteries were resected from the subjects who consisted
      of 12 men and 3 women, ranging in age from 39 to 84 yr. The femoral and posterior
      tibial arteries were resected from the subjects, consisting of 15 men and 5
      women, ranging in age from 25 to 88 yr. The element content of the arteries was
      analyzed by inductively coupled plasma-atomic emission spectrometry. It was found
      that there were extremely significant direct correlations among the average
      contents of calcium, phosphorus, and magnesium in the 18 kinds of the Thai
      artery, but no significant correlations were found between the average contents
      of sulfur and elements, such as calcium, phosphorus, and magnesium. These results
      were in agreement with those of the Japanese arteries. Therefore, it was
      suggested that there was no significant difference between the arteries of the
      Thai and the Japanese in the relationships among calcium, phosphorus, sulfur, and
      magnesium.

PMID- 15475620
TI  - Analyses of impact of metal ion contamination on carp (Cyprinus carpio L.) gill
      cell suspensions.
AB  - The decline in fish population because of water contamination is problem. As a
      result of direct exposure in water, it has been readily accepted that the gills
      are the main site of water contamination and toxicity (e.g., metal ions). In the
      present study, we investigated metal ion contamination on the functional capacity
      of carp gill cells with antioxidant interactions in an in vitro study. The extent
      of cellular membrane damage, lipid peroxidation (LPO) (as TBARS levels), and
      glutathione (GSH) content were investigated after the addition of two metal ion
      compounds (viz., CuSO(4) and HgCl(2)) in various concentrations (300, 500, 700,
      1000, and 3000 microM) to gill cell preparation of the freshwater fish carp
      (Cyprinus carpio L.) with modulations by bovine serum albumin (BSA) (0.5% and
      1.0%) and dimethyl sulfoxide (DMSO) (0.5%) as free-radical scavengers. The Comet
      assay technique was also performed for the highest concentrations of the two
      mentioned metal ions as an index of DNA breaks. The outcomes were as follows: (1)
      Copper and mercury increased the rate of LPO dose dependently (r=+0.995 and
      r=+0.993, respectively; p<0.001), but the GSH content was only marginally
      affected (r = -0.787 and r = -0.844, respectively; p <0.05). (2) Depletion of GSH
      molecules by copper had a wider range than mercury. (3) In the highest
      concentration of metal ions (3000 microM), both DMSO and 1.0% BSA showed a pro
      oxidative potential to elevate the levels of TBARS (p<0.001), but for other
      concentrations when supplemented with three scavengers, a fall in the levels of
      the latter was found. (4) The addition of 1.0% BSA to medium containing 3000
      microM of metal ions caused a significant decline in GSH content (p<0.01). (5)
      Copper and mercury could cause a high rate of DNA breaks (single stranded) in
      carp gill cell suspensions as a Comet appearance. These findings indicate that
      copper and mercury have a deleterious influence on membrane integrity and GSH
      content in a relatively dose-dependent manner. The complexes of metal ions and
      thiol (SH) residues of cell proteins could also act as a potential cell toxicant
      leading to disturbances in cell functions causing cell death. DNA fragmentation
      is frequent in metal ion contamination.

PMID- 15475621
TI  - Role of zinc on lipid peroxidation and antioxidative enzymes in intestines of
      ethanol-fed rats.
AB  - This study was undertaken to investigate the effects of zinc on lipid
      peroxidation and various antioxidative enzymes in the intestines of male Wistar
      rats fed on ethanol. It was observed that NADPH-dependent lipid peroxidation (LP)
      was significantly increased upon ethanol treatment for 4 and 8 wk. The
      concentration of glutathione as well as the activities of catalase, superoxide
      dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR)
      were also found to be significantly increased upon ethanol feeding at all of the
      treatment intervals. The glutathione levels were found to be further elevated
      upon combined zinc and ethanol treatments. Interestingly, the administration of
      zinc to ethanol-fed rats was able to bring down the elevated levels of LP,
      catalase, SOD, and GPx, thus indicating the antiperoxidative potential of zinc
      under such conditions.

PMID- 15475622
TI  - Serotonin in pain and analgesia: actions in the periphery.
AB  - The purpose of this article is to summarize recent findings on the role of
      serotonin in pain processing in the peripheral nervous system. Serotonin (5
      hydroxtryptamine [5-HT]) is present in central and peripheral serotonergic
      neurons, it is released from platelets and mast cells after tissue injury, and it
      exerts algesic and analgesic effects depending on the site of action and the
      receptor subtype. After nerve injury, the 5-HT content in the lesioned nerve
      increases. 5-HT receptors of the 5-HT3 and 5-HT2A subtype are present on C
      fibers. 5-HT, acting in combination with other inflammatory mediators, may
      ectopically excite and sensitize afferent nerve fibers, thus contributing to
      peripheral sensitization and hyperalgesia in inflammation and nerve injury.

PMID- 15475623
TI  - The physiological role of kainate receptors in the amygdala.
AB  - The kainate subtype of glutamate receptors has received considerable attention in
      recent years, and a wealth of knowledge has been obtained regarding the function
      of these receptors. Kainate receptors have been shown to mediate synaptic
      transmission in some brain regions, modulate presynaptic release of glutamate and
      gamma-aminobutyric acid (GABA), and mediate synaptic plasticity or the
      development of seizure activity. This article focuses on the function of kainate
      receptors in the amygdala, a brain region that plays a central role in emotional
      behavior and certain psychiatric illnesses. Evidence is reviewed indicating that
      postsynaptic kainate receptors containing the glutamate receptor 5 kainate
      receptor (GLUk5) subunit are present on interneurons and pyramidal cells in the
      basolateral amygdala and mediate a component of the synaptic responses of these
      neurons to glutamatergic input. In addition, GLUk5-containing kainate receptors
      are present on presynaptic terminals of GABAergic neurons, where they modulate
      the release of GABA in an agonist concentration-dependent, bidirectional manner.
      GLUk5-containing kainate receptors also mediate a longlasting synaptic
      facilitation induced by low-frequency stimulation in the external capsule to the
      basolateral nucleus pathway, and they appear to be partly responsible for the
      susceptibility of the amygdala to epileptogenesis. Taken together, these findings
      have suggested a prominent role of GLUk5-containing kainate receptors in the
      regulation of neuronal excitability in the amygdala.

PMID- 15475624
TI  - Regulation of antidepressant activity by cAMP response element binding proteins.
AB  - Depression is a clinically and biologically heterogeneous disease that is one of
      the most prevalent and costly psychiatric disorders. It is the leading cause of
      disability regarding job performance and burden on family members in the United
      States and worldwide. Although the therapeutic efficacy of antidepressant drugs
      has been recognized for years, the exact molecular mechanisms of action remain
      elusive, making the systematic approach to the development of new drugs
      difficult. The acute increases in levels of monoamines brought about by various
      classes of antidepressants cannot account for the requirement of repeated,
      chronic administration for up to 2-6 wk before treatment benefits become evident.
      Furthermore, despite their efficacy, current antidepressant drugs improve
      symptoms in only 60% of patients treated. The development of new and better
      therapies depends on a thorough understanding of the neurobiology of depression
      and the molecular mechanisms underlying antidepressant drug action. Early studies
      focusing on alterations in the levels of receptors and second messengers helped
      define the important signaling pathways initiated by these drugs, whereas recent
      molecular studies suggested that long-term adaptations in cellular signaling
      mechanisms may be required for the onset and/or maintenance of antidepressant
      effects. Attention has now focused on downstream targets of Ca++ and cyclic
      adenosine monophosphate (cAMP) in the cell, such as the activation of
      transcription factors. This article discusses the transcription factor cAMP
      response element binding protein and a related protein, cyclic AMP response
      element modulator, and their roles as molecular mediators of antidepressant
      action.

PMID- 15475625
TI  - Brain endothelial cells as pharmacological targets in brain tumors.
AB  - The blood-brain barrier contributes to brain homeostasis by controlling the
      access of nutrients and toxic substances to the central nervous system (CNS). The
      acquired brain endothelial cells phenotype results from their sustained
      interactions with their microenvironment. The endothelial component is involved
      in the development and progression of most CNS diseases such as brain tumors,
      Alzheimer's disease, or stroke, for which efficient treatments remain to be
      discovered. The endothelium constitutes an attractive therapeutical target,
      particularly in the case of brain tumors, because of the high level of
      angiogenesis associated with this disease. Drug development based on targeting
      differential protein expression in the vasculature associated with normal tissues
      or with disease states holds great potential. This article highlights some of the
      growing body of evidence showing molecular differences between the vascular bed
      phenotype of normal and pathological endothelium, with a particular focus on
      brain tumor endothelium targets, which may play crucial roles in the development
      of brain cancers. Finally, an overview is presented of the emerging therapies for
      brain tumors that take the endothelial component into consideration.

PMID- 15475628
TI  - Parenting adolescents.

PMID- 15475626
TI  - Cytoplasmic tail adaptors of Alzheimer's amyloid-beta protein precursor.
AB  - Alzheimer's disease is characterized pathologically by senile plaques in the
      brain. The major component of senile plaques is amyloid-beta (Abeta), which is
      cleaved from Alzheimer's Abeta protein precursor (AbetaPP). Recently, information
      regarding the cytoplasmic tail of AbetaPP has started to emerge, opening up
      various insights into the physiological roles of AbetaPP and its pathological
      role in Alzheimer's disease. The cytoplasmic domain of AbetaPP shares the
      evolutionarily conserved GYENPTY motif, which binds to a number of adaptor
      proteins containing the phosphotyrosine interaction domain (PID). Among the PID
      containing proteins, this article focuses on four groups of adaptor proteins of
      AbetaPP: Fe65, X11, mDab1, and c-Jun N-terminal kinase-interacting protein
      1b/islet-brain 1.

PMID- 15475629
TI  - Issues in pediatric tuberculosis under DOTS strategy.

PMID- 15475627
TI  - Linkage between the proteasome pathway and neurodegenerative diseases and aging.
AB  - During aging, the production of free radicals increases. This can result in
      damage to protein, the accumulation of which is characteristic of the aging
      process. This questions the efficacy of proteolytic systems. Among these systems,
      the proteasome and the adenosine triphosphate-ubiquitin-dependent pathway have
      been shown to play an important role in the elimination of abnormal proteins.
      There are two major steps in the ubiquitin-proteasome pathway: the conjugation of
      a polyubiquitin degradation signal to the substrate and the subsequent
      degradation of the tagged protein by the 26S proteasome. The 26S proteasome is
      build-up from the 20S proteasome, which is a cylinder-shaped multimeric complex,
      and two additional 19S complexes. The 20S proteasome can also bind to 11S
      regulator and is then implicated in antigen presentation. These regulators confer
      a high adaptability on proteasome. With advancing age, predisposition to
      neurodegenerative diseases increases. These diseases are also characterized by
      protein aggregation. Several findings such as the presence of ubiquinated
      proteins, usually broken down by proteasomes, and genetic anomalies involving the
      ubiquitin-proteasome system (parkin, UCH-L1) suggest a link between the ubiquitin
      proteasome pathway and the genesis of these diseases.

PMID- 15475630
TI  - Is C-reactive protein level useful in differentiating infected from uninfected
      neonates among those at risk of infection?
AB  - OBJECTIVE: To document effects of intrapartum risk factors for early onset sepsis
      (EOS) on CRP levels in neonates and to assess the suitability of this test in
      diagnosing EOS. DESIGN: Cohort study. SETTING: Labour and post natal wards in a
      tertiary level teaching hospital in India. SUBJECTS: 250 neonates at risk of
      developing infection. METHODS: CRP levels in cord blood and neonatal blood at 24
      hrs were estimated using commercial kits. Babies were observed for signs of
      sepsis for at least 48 hours. RESULTS: Seven (2.8 Percent) neonates had elevated
      CRP levels in the cord blood. At 24 hours, 102 (40.8 Percent) babies had elevated
      levels. Elevated cord CRP levels was significantly associated with rupture of
      membranes for 24 hours (p =0.04), labour more than 12 hours (p = 0.002), and
      maternal fever (p = 0.01). At 24 hours, elevated CRP levels were associated with
      primiparity (p= 0.006), more than three vaginal examinations after membrane
      rupture (p=0.02), meconium staining of amniotic fluid (p =0.02) and amnioinfusion
      (p =0.02). Ten (4 Percent) babies developed EOS. The negative predictive value
      for elevated CRP levels at 24 h was 99 Percent. CONCLUSION: Several intrapartum
      risk factors for EOS can cause elevation in CRP levels. However, this test may be
      useful in excluding infection.

PMID- 15475631
TI  - Management of pediatric tuberculosis under the Revised National Tuberculosis
      Control Program (RNTCP).

PMID- 15475632
TI  - Optimal care for asthmatic children--do we need special clinics?

PMID- 15475633
TI  - An outbreak of hospital acquired diarrhea due to Aeromonas sobria.
AB  - Six children admitted in a 18 bedded hematology-oncology unit, developed acute
      diarrhea in a four week period between March and April 2001. Salmonella
      senftenberg was the additional pathogen in the stool sample of one patient who
      developed cola colored urine and pneumonia in the course of his illness. All the
      Aeromonas strains had a similar biotype and antibiogram. The diarrhea subsided
      spontaneously in two children whilst three responded to antimicrobial therapy.
      One patient sought discharge and did not return for a follow up. Aeromonas sobria
      with a similar profile as the isolates from the patients could be isolated from
      only one of several environmental sites. The outbreak could be contained by
      appropriate interventional measures.

PMID- 15475634
TI  - Relationship between BCG scar size and asthma in children?
AB  - OBJECTIVE: This case control study was conducted to evaluate any association
      between the BCG scar size and occurrence of asthma among children between 6-14
      years of age. METHODS: Cases consisted of 90 asthmatic children. Control group
      included 90 non-asthmatic children from the emergency room service of the same
      hospital. The BCG scar was measured as the average of the transverse and
      longitudinal diameters. RESULTS: The results showed that asthmatic subjects have
      a 3.2 times greater risk exhibiting a scar diameter of less than 5mm than non-
      asthmatic subjects (CI 95 percent = 1.40 - 7.63 P < 0.01). CONCLUSION: It was
      concluded that asthmatic children and adolescents exhibited a greater frequency
      of an BCG scar diameter of less than 5mm than non-asthmatics. Clinical
      significance of this observation is uncertain.

PMID- 15475635
TI  - Immunogenicity of low dose intradermal hepatitis B vaccine and its comparison
      with standard dose intramuscular vaccination.
AB  - OBJECTIVE: A prospective study was carried out in the well baby and immunization
      clinics of tertiary care hospital to compare the immunogenicity of low dose
      hepatitis B vaccine (HBV) given intradermally versus standard dose given
      intramuscularly. METHODS: One hundred ninety six term, healthy, Australia antigen
      negative and exclusively breast fed babies were allocated into two groups in a
      simple randomized manner. In group I, hepatitis B vaccine was given in low dose
      (2 mcg) by intradermal route whereas in group II it was administered in standard
      dose (10 mcg) by intramuscular route. Diphtheria, pertussis, tetanus (DPT) and
      oral polio vaccine (OPV) were co-administered with HBV in both the groups at 6,
      10 and 14 weeks of age at different sites. One hundred seventy seven infants
      could be regularly followed up and tested for anti-HBs titres by third generation
      ELISA test using mono-ELISA anti-HBs 3.0 kits. Geometric mean titres of anti-HBs
      were estimated in each group and compared. Student's t-test was used for
      statistical analysis. RESULTS: Seroprotective anti-HBs titres (titre greater than
      10 mIU/mL) were achieved in 87 of 88 (98.8 percent) children having received
      intramuscular doses as compared to 82 of 89 (92.1 percent) children in the
      intradermal group. The geometric mean titres of the intradermal group were 92.71
      mIU/mL (95 percent C.I. 68.85-124.85), significantly lower than 331.66 mIU/mL (95
      percent C.I. 245.12-448.78), noticed in the intramuscular group. There were no
      significant adverse reactions in both the groups. Hepatitis B vaccine is
      immunogenic when co-administered with DPT and OPV vaccine. The intradermal
      hepatitis B administration is less effective with lower immunogenicity than the
      intramuscular vaccination.

PMID- 15475636
TI  - Category based treatment of tuberculosis in children.
AB  - BACKGROUND: Childhood tuberculosis is treated with multiple regimens for
      different clinical manifestations. World Health Organization has suggested a
      category-based treatment of tuberculosis that focuses on adult type of illness.
      To include children as DOTS beneficiaries, there is a need to assess the
      feasibility of classification and treatment of various types of childhood
      tuberculosis in different categories. METHODS: The study was conducted in the
      Pediatric Tuberculosis (TB) Clinic of a tertiary care hospital in North India.
      All children registered in the TB clinic were classified in four categories,
      similar to the categorization in World Health Organization's guidelines for
      treatment of tuberculosis in adults. All children with freshly diagnosed serious
      form of tuberculosis were included in category I. Category II included patients
      who had treatment failure, had interrupted treatment, relapse cases and those who
      were suspected to have drug resistant tuberculosis. Patients with primary
      pulmonary complex (PPC), single lymph node tuberculosis, minimal pleural effusion
      and isolated skin tuberculosis were included in category III. Category IV
      included patients who did not improve or deteriorated despite administration of 5
      drugs (as per Category II) for at least 2 months. RESULTS: A total of 459
      patients were started on antituberculosis drugs and were available for analysis.
      Pulmonary tuberculosis was the commonest followed by lymph node tuberculosis.
      Identification of AFB was possible only in 52 (11 percent) of the patients and
      was more commonly seen in lymph node tuberculosis. The mean age of the children
      was 93 months and sex distribution was almost equal. 323 patients were in
      category I, 12 in category II, 120 in category III and 4 in category IV. 365 (80
      percent) children completed the treatment. Of these, 302 (82.7 percent) were
      cured with the primary regimen assigned to them in the beginning, 54 (14.8
      percent) required extension of treatment for 3 months and 9 (2.5 percent)
      patients required change in the treatment regimen. Side effect in form of
      hepatotoxicity was observed in 12 (2.6 percent) patients and was significantly
      more in patients who were getting category IV treatment. CONCLUSION: It is
      feasible to classify and manage various types of tuberculosis in children in
      different categories similar to WHO guidelines for adult tuberculosis.

PMID- 15475637
TI  - Seronegative neonatal myasthenia gravis in one of the twins.
AB  - Neonatal myasthenia gravis has been described as a transient condition affecting
      only a small percent of neonates. We report a twin gestation in a seronegative
      mother with myasthenia gravis, in which only one twin was affected.

PMID- 15475638
TI  - Homocystinuria: a rare cause of megaloblastic anemia.
AB  - We present an eight-year-old boy who initially presented to us with megaloblastic
      anemia and subsequently developed dislocation of lens. The child had a positive
      sodium nitroprusside test and homocystinuria. He was diagnosed to have
      homocystinuria type 1. His anemia improved on oral pyridoxine and folic acid
      therapy. Homocystinuria should be remembered as a cause of megaloblastic anemia.

PMID- 15475639
TI  - Griscelli syndrome: Rab 27a mutation.
AB  - An infant with partial albinism was suspected to have Chediak-Higashi syndrome
      because two of his elder siblings had albinism and died in childhood following
      accelerated phase. Detailed investigations of blood, hair and skin of the proband
      revealed that he had Griscelli syndrome.

PMID- 15475640
TI  - Guillain-Barre syndrome following dengue fever.
AB  - Guillain-Barre syndrome is a post infectious polyradiculoneuropathy. It is
      equally prevalent in both the adult and the pediatric populations. Guillain-Barre
      syndrome following dengue fever is not a classically described entity and has not
      been reported in children.

PMID- 15475641
TI  - Facilitating behavioral change for acceptance of oral polio vaccine.
AB  - A child aged 26 months could not be vaccinated initially during pulse polio
      immunisation due to parental fear of untoward side effects. Owning responsibility
      of child's welfare, in-depth counseling and involvement of community leaders are
      crucial in this regard.

PMID- 15475642
TI  - Jeune syndrome.

PMID- 15475643
TI  - Aplasia cutis congenita.

PMID- 15475644
TI  - Missed and delayed diagnosis of neonatal meningitis.

PMID- 15475645
TI  - Does arsenic consumption influence the age at menarche of woman.

PMID- 15475646
TI  - Evaluation of IPPI coverage survey in two districts of Bihar.

PMID- 15475647
TI  - Phenobarbital toxic levels in a nursing neonate.

PMID- 15475648
TI  - Ascites--an under-reported finding in enteric fever?

PMID- 15475649
TI  - Preventive education against HIV/ AIDS in the schools of Iran.

PMID- 15475650
TI  - Adolescent friendly health.

PMID- 15475651
TI  - Subdural effusion or empyema in infants.

PMID- 15475652
TI  - Rapid enteral feeding in preterm neonates: NEC and survival.

PMID- 15475653
TI  - Autism spectrum disorders.

PMID- 15475655
TI  - Adrenal steroid hormones and metaphyseal bone in children.
AB  - BACKGROUND/OBJECTIVES: The responses of metaphyseal bone tissue to physiological
      variations of endogenous adrenal steroid hormones during childhood are unclear.
      Therefore, we studied potential hormonal influences in children before the
      appearance of pubic hair (onset of pubarche). METHODS: Excretions of major
      glucocorticoid metabolites (C21), cortisol, sum of adrenarchal
      dehydroepiandrosterone and its immediate 16-hydroxylated metabolites (DHEA&M),
      and 5-androstene-3beta,17beta-diol (hermaphrodiol) were analyzed in a cross
      sectional study in 24-hour urine samples of 109 healthy boys and girls, aged 6-13
      years, using steroid profiling by gas chromatography-mass spectrometry. Total and
      trabecular volumetric bone mineral densities, bone mineral content (BMC) and bone
      strength strain index were determined with peripheral quantitative computed
      tomography at the distal forearm. RESULTS: In multiple regression analyses
      significant associations with the metaphyseal radius were seen for grip force,
      age, or BMI depending on gender and bone variable analyzed. DHEA&M did not
      contribute to the explanation of the variance of any bone variable. However,
      hermaphrodiol positively explained a significant part of variation of bone
      mineral densities, and BMC (p < 0.01) in girls. Significantly negative
      associations with all bone variables were seen in boys for cortisol. CONCLUSIONS:
      The steroid hormones, cortisol and hermaphrodiol, in their physiological ranges,
      but not the adrenarche marker DHEA&M, appear to associate with metaphyseal bone
      in a sex-dependent manner during childhood.

PMID- 15475654
TI  - Effect of the long-term treatment with trandolapril on endoglin expression in
      rats with experimental renal fibrosis induced by renal mass reduction.
AB  - BACKGROUND: Endoglin is a membrane glycoprotein that regulates TGF-beta1
      signaling. Previous studies have revealed that endoglin is upregulated in several
      models of experimental fibrosis, and that endoglin expression can counteract the
      fibrogenic effects of TGF-beta1. As treatment with angiotensin converting enzyme
      (ACE) inhibitors reduces renal fibrosis by mechanisms that are, in part, not
      dependent on angiotensin II blockade, we have assessed the hypothesis that this
      effect could be mediated by endoglin upregulation. METHODS: We have used the 5/6
      nephrectomy renal mass reduction (RMR) model of renal fibrosis in rats treated
      (RMR+T) or not treated with the ACE inhibitor trandolapril (0.7 mg/kg/day). One,
      3 and 5 months after RMR, mean arterial pressure and renal function were
      measured. In addition, renal fibrosis was evaluated quantitatively and endoglin,
      TGF-beta1, collagen type I and collagen type IV expression was assessed by
      Northern blot and immunohistochemistry. RESULTS: RMR induced a progressive
      increase in mean arterial pressure, urinary protein excretion and glomerular and
      tubulointerstitial fibrosis, which is accompanied by an increased expression of
      TGF-beta1, endoglin and collagen types I and IV. Trandolapril treatment reduced
      systemic blood pressure and lessened proteinuria after RMR, as well as expression
      of TGF-beta1, endoglin and collagens. CONCLUSION: The present study demonstrates
      an increased TGF-beta1, endoglin, collagen type I and collagen type IV expression
      in rats with severe hypertension and renal damage. The effect of trandolapril to
      decrease renal fibrosis seems to be based in a reduced TGF-beta1 expression but
      not in an increased expression of endoglin.

PMID- 15475657
TI  - Unilateral battery depletion in Parkinson's disease patients treated with
      bilateral subthalamic nucleus deep brain stimulation may require urgent surgical
      replacement.
AB  - We describe 2 patients with advanced Parkinson's disease (PD) treated with
      bilateral deep brain stimulation of the subthalamic nucleus in whom unilateral
      stimulator battery depletion resulted in the rapid appearance of disabling PD
      symptoms (severe rigidity, bradykinesia and gait difficulty). Both patients did
      not respond to high doses of dopaminergic medications and were restored to their
      previous level of function only with battery replacement. One patient developed a
      deep vein thrombosis and pulmonary emboli as a result of prolonged immobility.
      Although extreme worsening of PD secondary to battery depletion may be rare, such
      patients should have their stimulators replaced promptly.

PMID- 15475658
TI  - Pranlukast inhibits NF-kappaB activation and MUC2 gene expression in cultured
      human epithelial cells.
AB  - Pranlukast is a selective cysteinyl leukotriene(1 )(cysLT(1)) receptor
      antagonist, and is now widely used in the treatment of asthma. The anti-asthmatic
      effect of pranlukast may be rendered not only by antileukotriene activity, but
      also by other pharmacological activity. This study was designed to investigate
      whether pranlukast had inhibitory effects on nuclear factor-kappaB (NF-kappaB)
      activation and mucin gene expression in cultured human epithelial cells.
      Luciferase assay was mainly used for analysis. Cultured epithelial cells were
      transfected with NF-kappaB luciferase vector, MUC2 or MUC5AC luciferase vectors.
      Lipopolysaccharide (LPS) significantly increased NF-kappaB activation in NCI-H292
      cells, which was inhibited by the pretreatment by pranlukast in a dose-dependent
      manner. Either LTD(4) or pranlukast alone did not increase NF-kappaB activation
      in NCI-H292 cells. Pranlukast also inhibited NF-kappaB activation induced by
      phorbol 12-myristate 13-acetate (PMA). Pranlukast also significantly inhibited
      LPS-induced MUC2 mRNA expression by reverse transcription-polymerase chain
      reaction (RT-PCR) analysis in NCI-H292 cells. Pranlukast also inhibited LPS
      induced MUC2 gene expression in HM3-MUC2 cells. However, pranlukast did not
      inhibit MUC5AC gene transcription activity induced by lipoteichoic acid (LTA) in
      NCI-H292 cells. These results suggest that pranlukast may inhibit NF-kappaB
      activation and MUC2 gene transcription through pathways distinct from cysLT(1)
      receptor antagonism in cultured human epithelial cells.

PMID- 15475659
TI  - In situ characterization of gonadotropin- releasing hormone-I, -III, and glutamic
      acid decarboxylase expression in the brain of the sea lamprey, Petromyzon
      marinus.
AB  - The distribution of lamprey gonadotropin-releasing hormone (GnRH)-I and -III has
      been extensively characterized by immunocytochemistry in the forebrain of the sea
      lamprey, Petromyzon marinus. However, the cellular location of lamprey GnRH-III
      mRNA expression by in situ hybridization in the lamprey brain has not been
      determined. We show for the first time the location of expression of lamprey GnRH
      III, as well as provide a more comprehensive in situ study of lamprey GnRH-I and
      glutamic acid decarboxylase (GAD; GABA-synthesizing enzyme) mRNA expression in
      the brain of the lamprey in different reproductive life stages. Colorimetric and
      dual-label fluorescent amplification methods of in situ hybridization were used
      on brain tissue sections of adult, juvenile, and larval sea lamprey. In each life
      stage of the lamprey, expression of lamprey GnRH-I was shown in the preoptic area
      (POA) and the hypothalamus forming the characteristic arc-like cell population
      extending from the preoptic nucleus (NPO) to the neurohypophysis. Lamprey GnRH
      III expression was also seen in the POA of each life stage in close proximity to
      lamprey GnRH-I mRNA containing neurons. GAD expression was shown in distinct cell
      clusters in and around the POA, in the olfactory bulb, in the dorsal thalamus
      beneath the habenular region, and also in the ventral-medial hypothalamus
      stretching from the periventricular region to the anterior portion of the
      rhombencephalon. Using dual-label in situ hybridization, we have shown that
      lamprey GnRH-I and -III mRNA are colocalized in the same cells in the POA in
      adult lampreys. Dual-label in situ hybridization also showed close proximity of
      GAD mRNA containing neurons and GnRH containing neurons in the POA. These data
      suggest that gamma-aminobutyric acid (GABA) may directly affect GnRH release in
      the brain of the sea lamprey.

PMID- 15475660
TI  - Lipopolysaccharide contamination of beta-lactoglobulin affects the immune
      response against intraperitoneally and orally administered antigen.
AB  - BACKGROUND: Microbial components in the environment are potent activators of the
      immune system with capacity to shift the active immune response towards priming
      of Th1 and/or Th2 cells. Lipopolysaccharide (LPS), a cell-wall component of Gram
      negative bacteria, is extensively present in food products like cow's milk. It is
      not well established, however, how this presence of LPS affects oral tolerance
      induction. METHODS: We studied the effect of LPS contamination in a commercial
      preparation of the cow milk protein beta-lactoglobulin (beta-LG) on antigen
      specific immune responses. IgG1/IgG2a production upon intraperitoneal
      immunization without adjuvant was measured, and oral tolerance induction against
      beta-LG after administration of either an aqueous solution or water-in-oil (w/o)
      emulsion of beta-LG was evaluated. RESULTS: LPS contamination of beta-LG provoked
      a beta-LG-specific IgG2a response, as well as an enhanced beta-LG-specific IgG1
      response upon intraperitoneal immunization. Oral tolerance induction to beta-LG
      was induced by aqueous solutions of beta-LG with and without LPS administration.
      Conversely, oral administration of w/o-emulsified beta-LG prevented oral
      tolerance to beta-LG only when the beta-LG was contaminated with LPS.
      CONCLUSIONS: LPS contamination of an aqueous protein solution does not affect
      oral tolerance induction, whereas LPS present in emulsion prevents oral tolerance
      induction towards the food protein.

PMID- 15475661
TI  - Tumor necrosis factor-alpha-induced nitric oxide restrains the apoptotic response
      of anterior pituitary cells.
AB  - We previously reported that tumor necrosis factor-alpha (TNF-alpha) inhibits cell
      proliferation whereas it stimulates apoptosis of anterior pituitary cells in an
      estrogen-dependent manner. Also, we showed that nitric oxide (NO) mediates the
      inhibitory effect of TNF-alpha on prolactin release. Here, we studied the effect
      of TNF-alpha on nitric oxide synthase (NOS) activity and expression in anterior
      pituitary cells from cycling and ovariectomized (OVX) rats, and the role of NO in
      TNF-alpha induced apoptosis of anterior pituitary cells. NOS activity was higher
      in anterior pituitary cells from rats in proestrus than in diestrus and was
      stimulated by 17beta-estradiol (10(-9) M, E2). TNF-alpha (50 ng/ml) stimulated
      NOS activity in anterior pituitary cells from rats at both stages of the estrous
      cycle and in cells from OVX rats cultured either with or without E2. Inducible
      NOS (iNOS) gene expression was higher in anterior pituitary cells from rats in
      proestrus than in diestrus and its expression was enhanced by TNF-alpha. Acute
      administration of E2 to OVX rats increased endothelial NOS (eNOS) expression in
      the anterior pituitary gland. Also, E2 increased eNOS mRNA in dispersed anterior
      pituitary cells from OVX rats, and this effect was blocked by TNF-alpha. nNOS
      expression in the anterior pituitary gland was higher at proestrus than at
      diestrus but eNOS expression was similar at both stages. TNF-alpha decreased eNOS
      mRNA in anterior pituitary cells from rats at proestrus or diestrus. In anterior
      pituitary cells from OVX rats, TNF-alpha failed to induce apoptosis but was able
      to induce it when cells were incubated with NAME or NMMA, NOS inhibitors that did
      not affect cell viability per se. In the presence of E2, NAME induced apoptosis
      and enhanced the proapoptotic effect of TNF-alpha. In conclusion, our study shows
      that TNF-alpha upregulates iNOS gene expression whereas it downregulates estrogen
      induced eNOS expression in anterior pituitary cells. Endogenous NO may restrain
      rather than mediate the proapoptotic effect of TNF-alpha in anterior pituitary
      cells.

PMID- 15475662
TI  - Mineralocorticoid treatment upregulates the hypothalamic vasopressinergic system
      of spontaneously hypertensive rats.
AB  - Mineralocorticoid effects in the brain include the control of cardiovascular
      functions, induction of salt appetite, interaction with the vasoactive
      neuropeptides arginine vasopressin (AVP) and angiotensin II and development or
      aggravation of hypertension. In this regard, mineralocorticoids may play a
      pathogenic role in rats with a genetic form of hypertension (spontaneously
      hypertensive rats, SHR). Our objective was to compare the response of the
      hypothalamic vasopressinergic system to mineralocorticoid administration in SHR
      and control Wistar-Kyoto (WKY) rats. Sixteen-week-old male SHR showing a systolic
      blood pressure of 190 +/- 5 mm Hg and normotensive WKY rats (130 +/- 5 mm Hg)
      were treated subcutaneously with oil vehicle or a single 10-mg dose of
      deoxycorticosterone acetate (DOCA). After 2 h, rats were sacrificed and brains
      prepared for immunocytochemistry of Fos and vasopressin V1a receptor (V1aR) and
      for non-isotopic in situ hybridization of AVP mRNA. In the basal state, SHR
      demonstrated a higher number of AVP mRNA- and V1aR-immunopositive cells in the
      magnocellular division of the paraventricular hypothalamic nucleus (PVN) than WKY
      rats. After DOCA injection, SHR responded with a significant increase in both
      parameters with respect to vehicle-injected SHR. In WKY rats, DOCA was without
      effect on AVP mRNA although it increased the number of V1aR-positive cells.
      Changes in the number of Fos-positive nuclei were measured in the PVN, median
      preoptic nucleus (MnPO) and organum vasculosum of the lamina terminalis (OVLT), a
      circumventricular region showing anatomical connections with the PVN. In vehicle
      injected rats, the PVN of SHR showed a higher number of Fos-positive nuclei than
      in WKY rats, whereas after DOCA treatment, a significant increment occurred in
      the OVLT but not in the PVN or MnPO of the SHR group only. These data suggest
      that the enhanced response of the vasopressinergic system to mineralocorticoids
      may contribute to the abnormal blood pressure of SHR.

PMID- 15475663
TI  - Neonatal hyperthyrotropinemia in gestational diabetes mellitus and perinatal
      complications.
AB  - The aim of this study is to explore the relationship between high cord blood
      thyroid-stimulating hormone (TSH) level and in-utero stress to the fetus in
      gestational diabetes mellitus (GDM). Cord blood TSH results were analyzed in
      1,578 euthyroid infants from singleton pregnancies with GDM: 103 with elevated
      TSH (>16 mIU/l) and 1,475 with normal TSH. Maternal characteristics, pregnancy
      outcome and perinatal complications were compared between the two groups.
      Multiple logistic regression was used to study the association between high cord
      blood TSH level and various perinatal complications which reflect in-utero stress
      in GDM after adjusting for the confounding effects of parity, instrumental
      delivery, cesarean section and baby gender. High cord blood TSH level was found
      to be associated with the 1-min Apgar score <7 (OR 3.31, 95% CI 1.78-6.16), birth
      trauma (OR 3.44, 95% CI 1.11-10.69), neonatal jaundice requiring treatment (OR
      2.08, 95% CI 1.30-3.32), neonatal sepsis (OR 2.34, 95% CI 1.24-4.42), respiratory
      complications (OR 3.45, 95% CI 1.37-8.70), neurological complications (OR 8.01,
      95% CI 1.91-33.60) and overall perinatal morbidity (OR 2.41, 95% CI 1.58-3.67).
      Cord blood TSH level seems to be a better and independent indicator of the in
      utero stress to the fetus in GDM when compared to the commonly used sugar profile
      result and HbA1c level.

PMID- 15475664
TI  - Impact of choice of therapeutic strategy for acute cholecystitis on patient's
      health-related quality of life. Results of a randomized, controlled clinical
      trial.
AB  - BACKGROUND: The aim of this prospective, randomized study was to determine if
      health related quality of life is affected by the choice of surgical strategy in
      the management of acute cholecystitis. MATERIAL AND METHODS: After diagnostic
      workup, patients were randomized to one of two groups: (1) early laparoscopic
      cholecystectomy (i.e. within 7 days after onset of symptoms) or (2) initial
      conservative treatment followed by delayed laparoscopic cholecystectomy. Seventy
      four patients entered the early operation group and 71 patients were assigned to
      the delayed operation strategy. Assessments of quality of life were made at 1, 3
      and 6 months after surgery, and in the delayed operation group also one month
      after the initial conservative treatment. RESULTS: The gastrointestinal symptom
      scores were significantly better in three dimensions (diarrhea, indigestion,
      abdominal pain) one month after surgery for the acute operation group (p < 0.01).
      Three and 6 months after the operation we were unable to detect any significant
      differences between the groups. The patients in the delayed operation group did
      not appear to suffer from more symptoms in the period of time waiting for their
      elective operation. Psychological general well-being showed no major differences
      between the groups. CONCLUSION: Cholecystectomy in the acute phase of acute
      cholecystitis offers a significant reduction of gastrointestinal symptoms during
      the first postoperative month and to that associated improved quality of life in
      this group of patients.

PMID- 15475665
TI  - Prior heat acclimation confers protection against noise-induced hearing loss.
AB  - Exposure to intense noise stress can cause a permanent noise-induced hearing loss
      which is thought to be due to elevation of reactive oxygen species in excess of
      the inherent antioxidant mechanisms of the cell. However, preconditioning to low
      levels of stress of one type can activate cellular mechanisms leading to the
      elevation of antioxidant levels so that the cell is then better able to tolerate
      subsequent severe stress of a different type. This has been called cross
      tolerance. Here, we tested this hypothesis by acclimating rats to a moderate heat
      stress (30 days at 34 degrees C). The rats were exposed to 113 dB SPL noise for 3
      days (12 h/day) in three different groups: heat acclimated then noise exposed;
      noise exposed and then heat acclimated; heat acclimated, then noise exposed and
      then heat acclimated again. Permanent changes in auditory function--auditory
      nerve brainstem evoked responses (ABR) and distortion product otoacoustic
      emissions (DPOAEs)--were evaluated in each of these animals and compared with
      those in rats exposed to noise only and in control groups of rats. Statistical
      evaluation of the results showed that when assessed with ABR, each of the heat
      acclimated, noise-exposed groups was protected from the noise, even the group
      that was heat-acclimated after the noise exposure. When assessed with DPOAE,
      protection was statistically apparent only in the group that was heat acclimated,
      then exposed to noise, and not in the other groups. Thus, heat acclimation
      provides protection against permanent noise-induced hearing loss.

PMID- 15475666
TI  - Genes and languages.
AB  - Reconciling the genetic, linguistic and archaeological histories of humans will
      require linguists and geneticists to interact in the design and implementation of
      future research strategies. This paper discusses the issues involved in
      correlating these disciplines and highlights some of the problems involved. It is
      argued that correlation cannot be an a priori assumption, but must be proved
      prior to or as part of each investigation. An urgent need for hierarchical
      linguistic classifications is established and several possible methods are
      identified. Case studies include the Indo-European language family and Eurasian
      populations; the Nostratic hypothesis; and the history of Austronesia. General
      and specific factors responsible for correlations, or their absence, are
      considered in relation to autosomal, mitochondrial and Y-chromosome-specific data
      and human demography.

PMID- 15475667
TI  - Family communication about genetic risk: the little that is known.
AB  - Although family communication is important in clinical genetics only a small
      number of studies have specifically explored the passing on of genetic knowledge
      to family members. In addition, many of these present exploratory or tentative
      findings based upon small sample sizes, or data collected only a short time after
      testing. Nevertheless, if health professionals are to develop effective
      strategies to help patients' deal with communication issues, we need to know more
      about what actually happens in families. The aim of this commentary is to
      identify factors which appear to influence whether patients share information
      about genetic risk with relatives who are unaware of that risk, with whom they
      share it and how they go about it. The paper draws upon evidence and thinking
      from the disciplines of psychology (including family therapy), sociology,
      medicine and genetic counselling. It is presented under the following headings:
      disease factors, individual factors, family factors and sociocultural factors. It
      concludes by highlighting a number of key issues which are relevant for health
      professionals.

PMID- 15475668
TI  - Effects of individual and family functioning on interest in genetic testing.
AB  - OBJECTIVE: The present study reports on the important issue of how family
      communication and support regarding breast cancer risk affects interest in
      genetic testing and mental health. METHODS: Participants (n = 221) were women
      aged 18-74 who had at least one relative of Ashkenazi Jewish descent, no personal
      history of breast or ovarian cancer, and lived within 60 miles of Seattle, Wash.
      RESULTS: Communication about breast cancer risk was reported with very low
      frequency across all types of relatives. Women talked with their mothers and
      sisters more often than their fathers, brothers, or children. The only
      significant predictor of interest in genetic testing was the individual level
      variable of seeking social support. CONCLUSION: Social support needs might be a
      part of the genetic testing process.

PMID- 15475669
TI  - Public experiences, knowledge and expectations about medical genetics and the use
      of genetic information.
AB  - OBJECTIVE: The objectives of this study were (1) to explore public experiences,
      genetic knowledge, expectations of future medical genetic developments, and the
      attitudes towards the use of genetic information, and (2) to determine whether
      there are subject characteristics associated with these variables. METHODS:
      Participants (n = 1,308, age > or = 25 years) of a Dutch consumer panel were sent
      a questionnaire, specifically designed for this study. RESULTS: Response was 63%
      (817/1,308). A minority of respondents reported to know someone with a hereditary
      disease (34%) or to have used a genetic test (8%). Overall, 57% perceived a lack
      of genetic knowledge. In multivariate analyses, high self-rated knowledge,
      younger age, having heard of genetic testing, high educational level, female
      gender, having children living at home, being a health professional, and
      familiarity with genetic testing were positively associated with genetic
      knowledge. Future expectations of the consequences of developments in medical
      genetics varied between the subjects. The great majority expected great benefits
      for medical practice such as an increasing use of genetic aspects of disease for
      diagnosis or prevention. One fifth, mainly older people, anticipated a negative
      impact of genetic developments on society. The results also show that most people
      are reserved to share their genetic information with others, especially with
      regard to the wider public domain (e.g. industry and insurers) and employers.
      Remarkably, respondents were more willing to share their genetic information with
      scientific researchers (68%) than with their relatives (54%). CONCLUSION: This
      study suggests that although one fifth anticipates negative consequences of
      genetic developments, the great majority has high expectations about the
      increasing use of genetics in prevention, diagnosis and treatment of diseases. In
      developing educational programmes about genetic innovations in medicine,
      policymakers will have to take into account pre-existing lay knowledge, views and
      expectations of different groups of citizens towards these developments.

PMID- 15475670
TI  - Concerns over participation in genetic research among Malay-Muslims, Chinese and
      Indians in Singapore: a focus group study.
AB  - OBJECTIVE: This study was aimed at exploring and comparing peoples' concerns over
      donation of blood specimens for genetic research across three ethnic groups in
      Singapore: Malay-Muslims, Chinese and Indians. METHODS: We conducted 12 focus
      group sessions among 98 participants with 7-10 in each group. RESULTS: Concerns
      over donation of blood specimens for genetic research were diverse, with all
      ethnic groups expressing anxiety about breach of confidentiality, finding out
      that they have a disease and misuse of research for cloning. Other concerns
      included fear of pain, blood and needle pricks and misconceptions of adverse
      health effects such as weight gain from donating blood specimens. Malay-Muslims
      were generally concerned about the selection process, potential racial
      discrimination, and religious beliefs regarding blood storage while Chinese and
      Indians were concerned about giving blood to strangers and being inconvenienced
      by participating in research. CONCLUSION: Programmes to promote community
      participation in genetic research should address the diverse ethnic concerns,
      design ethnic-sensitive messages and involve the community.

PMID- 15475671
TI  - Age at postnatal diagnosis of down syndrome in the northern Netherlands for the
      period 1981-2000.
AB  - BACKGROUND: In live-born children with Down syndrome it may be very difficult for
      the clinician or midwife assisting at the delivery to recognise Down syndrome in
      newborn babies due to varying physical appearances. Meanwhile more and more
      therapeutical interventions become available that should start early in life. We
      were interested in the age at the postnatal diagnosis of Down syndrome, and found
      no literature on the subject. METHODS: We studied the age at the diagnosis of
      Down syndrome for live-born babies born in the period of 1981-2000 and registered
      by the European Registration of Congenital Anomalies in the northern part of The
      Netherlands. RESULTS: For 289 children, data on the age at the postnatal
      diagnosis were available, in 70.8% of whom there was suspicion of DS on the day
      of birth. In 1.7% of the cases, the diagnosis was made after 1 year. Place of
      birth and the specialty of the health worker assisting at the delivery were
      associated with age at diagnosis. When the child was delivered at hospital, 96.4%
      of the Down syndrome cases had been diagnosed within 1 month compared to 81.3%
      following home delivery. CONCLUSION: In some cases of Down syndrome in live-born
      babies, the diagnosis is made only after months or a year. The diagnosis was made
      faster in babies born in hospital compared to those born at home.

PMID- 15475673
TI  - Understanding perceptions of HIV risk among adolescents in KwaZulu-Natal.
AB  - Risk perception has been theorized to be an important antecedent for adopting
      protective behavior. It is a key construct of research applying the Health Belief
      Model and other behavior change models. In relation to HIV, risk perception is an
      indicator of perceived susceptibility to infection, a measure for one's
      understanding of AIDS transmission as well as willingness to consider behavioral
      changes. However, there remains much we do not know about what drives risk
      perception, especially among youth. This study identifies factors that influence
      the calculation of HIV-risk perception among a group of adolescents in South
      Africa. Data, collected in 1999 from 2,716 adolescents aged 14-22, are used to
      explore factors predicting risk perception. Logistic regression models suggest
      connectedness to parents and community for males and females, self-efficacy to
      use a condom among males, and living in a household with a chronically ill member
      for females are associated with HIV risk perception. We conclude that a greater
      understanding of the connection of adolescents to their communities and adults in
      their lives is needed, and ways in which programs can alter the environments in
      which adolescents form opinions, make choices, and act should be incorporated
      into program design.

PMID- 15475672
TI  - Religious involvement, coping, social support, and psychological distress in HIV
      seropositive African American mothers.
AB  - This study used a cross-sectional design to examine the role of religious
      involvement within a stress-process framework. Participants were 252 urban, low
      income HIV-seropositive African American mothers. The relationships among
      religious involvement, stress, coping responses, social support, and
      psychological distress were examined using structural equation modeling. The
      number of stressors reported by the mother was related to greater religious
      involvement, which in turn was negatively related to psychological distress.
      Furthermore, the results suggest that social support, active coping, and avoidant
      coping responses mediated the relationship between religious involvement and
      psychological distress. According to the present results, interventions to
      attenuate psychological distress in HIV-seropositive African American mothers
      might focus on increasing social support, promoting active coping, and decreasing
      avoidant coping. The present findings suggest that this may be accomplished, in
      part, by promoting involvement in religious institutions and practices. However,
      in light of the cross-sectional design used in the present study, and given that
      religion may have both positive and negative consequences, further research is
      needed to determine the extent to which promoting religiosity may increase or
      alleviate distress.

PMID- 15475674
TI  - Introducing and negotiating the use of female condoms in sexual relationships:
      qualitative interviews with women attending a family planning clinic.
AB  - Safe sex skills training often teach women to be assertive in condom use
      negotiations. However, it has been suggested that assertiveness training may be
      inappropriate for women who lack power in their sexual relationship. Our
      qualitative study of 62 women attending a family planning clinic explored various
      communication styles they used to introduce and negotiate female condom use in
      their sexual relationships. We further examined how different introduction and
      negotiation styles were related to actual use of the device. The device was
      introduced using a direct, semidirect, indirect, or nonverbal communication
      approach. Use of the female condom was negotiated by avoiding sex, using humor,
      discussing the possibility of using the condom, or being argumentative with
      partners. The outcome of introducing and negotiating female condom use was often
      mediated by other factors including partner characteristics, relationship power
      dynamics, situational context, and use of additional discourse strategies (e.g.,
      describing the female condom as a sexual toy or taking the opportunity to
      educated partners about the female condom). Less direct approaches appeared to be
      as effective in facilitating use of the female condom as more direct approaches.
      Female condom introduction and negotiation styles that continued to engage their
      partners by using additional discourse strategies led to more frequent use of the
      device. Implications of our findings for HIV risk reduction program development
      are discussed.

PMID- 15475675
TI  - The clinical significance of change in trauma-related symptoms following a pilot
      group intervention for coping with HIV-AIDS and childhood sexual trauma.
AB  - The association between sexual abuse and HIV risk is well documented, yet little
      empirical data exists on treatment approaches integrating the psychological
      impact of sexual abuse and HIV disease. This study examined the clinical
      significance of change on sexual-trauma-related stress following a coping group
      intervention study among 28 women and men with HIV-AIDS and a history of
      childhood sexual abuse. More than 75% of participants showed improvement on 1 or
      more subscales of the Trauma Symptom Inventory, with the majority of improvements
      within domains related to trauma symptoms and behavioral difficulties. Most
      observed gains were modest, but are considered meaningful in the context of
      stressors encountered by this disenfranchised sample, which was diverse with
      respect to race, sexual orientation, and psychiatric comorbidity. These
      preliminary findings support the need for the conduct of research trials to
      identify mental health and secondary prevention intervention models that can
      assist those with HIV-AIDS who have experienced childhood sexual abuse.

PMID- 15475676
TI  - The HIV Medication Self-Reported Nonadherence Reasons (SNAR) Index and its
      underlying psychological dimensions.
AB  - The purpose of this paper is to report on the construction of the HIV Medication
      Self-Reported Nonadherence Reasons (SNAR) index and its psychological correlates.
      Data were derived from a sample of 193 Swedish HIV-seropositive women and men
      receiving antiretroviral medications. Participants who reported dosing and/or
      scheduling and/or dietary instructions nonadherence in the past 7 days were
      presented with a modified AACTG list of 18 reasons for nonadherence. From these
      data, two conceptually and statistically independent factors were obtained, which
      accounted for 39% of the variance in the data. These factors were used as the
      basis for constructing two composite measures composing the SNAR index: the
      Medication concerns scale and the Routine disruption scale. The Medication
      concerns scale correlated significantly to suboptimal dose and scheduling
      adherence and Routine disruption scale with poorer dietary instructions
      adherence. Psychological distress was the best predictor of the SNAR index. The
      SNAR index has a clearly interpretable factor structure that allows the derived
      scales to be useful as multi-item measures of self-reported reasons for
      nonadherence to HIV antiretroviral medications. The psychological factors found
      to be associated with the index may imply a number of mental-health-related
      interventions to improve adherence, which deserve further exploration.

PMID- 15475677
TI  - Correlates of HIV antibody testing among a sample of injection drug users: the
      role of social and contextual factors.
AB  - As injection drug users (IDUs) continue to be infected by HIV, an important
      component of prevention efforts is the identification of factors that are
      associated with utilization of HIV testing programs. The purpose of this study
      was to identify correlates of HIV testing within the past 12 months among IDUs. A
      sample of 558 IDUs, recruited from street-based and community venues, completed a
      cross-sectional survey. Multivariate logistic regression indicates factors
      independently associated with having been tested recently, including social
      structural factors such as being incarcerated, having interactions with an HIV
      prevention outreach worker, and having used a case manager. Furthermore, main sex
      partner's testing status was positively associated with recent testing. Support
      of programs that are designed to serve hard-to-reach populations and target
      couples may be effective in increasing HIV testing among active IDUs.

PMID- 15475678
TI  - Using the internet to recruit rural MSM for HIV risk assessment: sampling issues.
AB  - The Internet is an emerging research tool that may be useful for contacting and
      working with rural men who have sex with men (MSM). Little is known about HIV
      risks for rural men and Internet methodological issues are only beginning to be
      examined. Internet versus conventionally recruited samples have shown both
      similarities and differences in their demographic characteristics. In this study,
      rural MSM from three sizes of town were recruited by two methods: conventional
      (e.g. face-to-face/snowball) or Internet. After stratifying for size of city,
      demographic characteristics of the two groups were similar. Both groups had ready
      access to the Internet. Patterns of sexual risk were similar across the city
      sizes but varied by recruitment approach, with the Internet group presenting a
      somewhat higher HIV sexual risk profile. Overall, these findings suggest the
      Internet provides a useful and low cost approach to recruiting and assessing HIV
      sexual risks for rural White MSM. Further research is needed on methods for
      recruiting rural minority MSM.

PMID- 15475679
TI  - Intimacy and sexual behavior among HIV-positive men-who-have-sex-with-men in
      primary relationships.
AB  - Unprotected anal intercourse among men-who-have-sex-with-men (MSM) occurs more
      frequently between partners in a primary relationship than between nonprimary
      partners. Although research supports the role of social support in risky sex,
      findings also suggest that the reasons associated with risky sex differ depending
      on both the relationship status and HIV-serostatus of MSM. This study assessed
      whether level of intimacy within a primary relationship helps to explain risky
      sex among a sample of 78 HIV-positive MSM currently involved in a primary
      relationship. Findings suggest that both drug use prior to sex and HIV status of
      the primary partner moderate the relationship between intimacy and sexual risk
      behaviors. Under levels of low drug use, greater intimacy functioned as a
      protective factor within seroconcordant relationships whereas it functioned as a
      risk factor within serodiscordant relationships. Implications for educational and
      clinical interventions are discussed.

PMID- 15475680
TI  - Persistence of inconsistent condom use: relation to abuse history and HIV
      serostatus.
AB  - This study longitudinally examines the relation between a history of experiencing
      childhood and adult physical or sexual abuse, and male condom use by women with
      or at risk for HIV. Abuse history and prospective condom use data were collected
      from 214 HIV infected and 189 uninfected women participating in the HIV
      Epidemiology Research Study (HERS) who were inconsistent condom users at baseline
      and received two safer sex counseling sessions. Analyses were conducted to assess
      the association between abuse history and condom use while controlling for
      sociodemographic variables and other risk factors. HIV-uninfected women with a
      history of adult physical abuse were five times less likely to report consistent
      condom use at 1-year follow-up than uninfected women without a history of abuse
      while holding control variables constant. Expectations of a negative reaction by
      the partner to suggested condom use did not explain this association. Though in
      the same direction as in uninfected women, abuse history was not significantly
      related to consistent condom use among HIV-infected women. These data indicate
      the need to develop risk prevention strategies tailored to uninfected women with
      a history of adult abuse. In lieu of specialized interventions, health care
      providers should assess women's abuse history and supplement HIV prevention
      counseling with mental health counseling when indicated.

PMID- 15475681
TI  - Changes in neuropsychological functioning with progression of HIV-1 infection:
      results of an 8-year longitudinal investigation.
AB  - Despite the advent of more effective treatments for HIV-1 infection, cognitive
      impairment is still frequent and questions remain regarding which areas of
      impairment are more common in the different disease stages. This study
      investigated cognitive performance over an 8-year period of time in 59 HIV-1
      seropositive (HIV-1+) men who were clinically asymptomatic at study entry, in
      comparison to a cohort of 55 HIV-1 seronegative (HIV-1-) men. Every 6 months we
      examined cognitive functioning in 5 domains-fine motor speed, attention, verbal
      memory, executive functioning, and speed of information processing. We found that
      patients with AIDS scored significantly worse on fine motor speed and speed of
      information processing than HIV-1- individuals and the HIV-1+ non-AIDS patients.
      In addition, the HIV-1+ non-AIDS patients performed more poorly than the HIV-1-
      group on speed of information processing. Depressive symptoms were also
      associated with diminished performance on measures of attention, executive
      functioning, and speed of information processing. Further research is needed to
      examine the effects of disease stage and depression on cognitive impairment in
      the era of new HIV treatments.

PMID- 15475682
TI  - Alpha-adrenergic receptor (alpha(2 A )) is colocalized in basal forebrain
      cholinergic neurons: a light and electron microscopic double immunolabeling
      study.
AB  - A variety of data suggest that noradrenaline and acetylcholine may interact in
      the basal forebrain, however no morphological studies have addressed whether
      indeed cholinergic neurons express adrenergic receptors. We have investigated the
      presence of alpha-adrenergic receptor subtype alpha2A-AR in cholinergic neurons
      of the basal forebrain. Cholinergic neurons were identified with an antibody
      against choline acetyltransferase and the receptor with a polyclonal antibody
      raised against a 47 amino acid fragment of the third intracellular loop of the
      alpha2A-AR. For double labeling at the light microscopic level the Ni-DAB/DAB
      technique was used, and for electron microscopy an immunoperoxidase/immunogold
      method was applied. We detected the alpha2A-AR protein in cholinergic as well as
      in non-cholinergic neurons. Almost half of all cholinergic neurons contained this
      adrenergic receptor. Double-labeled neurons were distributed throughout the
      rostro-caudal extent of the basal forebrain cholinergic continuum, including the
      medial septum, vertical and horizontal diagonal band nuclei, pallidal regions,
      substantia innominata and the internal capsule. Non-cholinergic neurons that
      expressed the alpha2A-AR outnumbered cholinergic/alpha2A-AR neurons by several
      factors. Electron microscopy confirmed the presence of alpha2A-AR in cholinergic
      neurons in the medial septum, vertical and horizontal diagonal band nuclei. Gold
      particles (10 nm) indicative of alpha2A-AR were diffusely distributed in the
      cytoplasm and accumulated in cytoplasmic areas near the Golgi complex and
      cysterns of the endoplasmic reticulum and were associated with the cellular
      membranes at synaptic and non-synaptic locations. Since many of the alpha2A
      AR+/non-cholinergic neurons we detected are likely to be GABAergic cells, our
      data support the hypothesis that noradrenaline may act via basal forebrain
      cholinergic and non-cholinergic neurons to influence cortical activity.

PMID- 15475683
TI  - Tri-dimensional morphometric analysis of astrocytic processes with high voltage
      electron microscopy of thick Golgi preparations.
AB  - A characteristic feature of the astrocytic processes is to assume the form of
      shin sheets or lamellate coverings of other brain constituents. We analyzed the
      extensive and finely divided processes of the protoplasmic astrocyte in the
      molecular layer of the rat dentate gyrus by means of computer electron tomography
      and stereo-photogrammetry using tilted high voltage electron microscope images of
      thick Golgi preparations. The surface area and volume of the astrocytic processes
      were measured and the surface/volume ratios were estimated. The surface/volume
      ratios of astrocytic processes in the neuropile ranged from 18.9 to 33.0 per
      microm, and the mean value was 26.2+/-5.0 per microm. The values were roughly
      comparable to those previously reported for the microdomain of Bergmann glia cell
      terminal processes in the rat cerebellum, which were estimated from
      reconstructions using thin serial section electron microscope images. The large
      surface to volume ratio of the astrocytic processes in the neuropile resulted
      from the lamellar nature of the processes interposed between other cellular
      elements, and may reflect the functional activities of the astrocyte. The results
      suggest the usefulness of the electron tomography and stereo-photogrammetry for
      three-dimensional morphometrical analysis of the astrocytic processes, although
      both techniques can be expected to be refined further in order to provide more
      precise measurements of these complicated processes.

PMID- 15475684
TI  - Tau epitope display in progressive supranuclear palsy and corticobasal
      degeneration.
AB  - Filamentous aggregates of the protein tau are a prominent feature of Alzheimer's
      disease (AD), progressive supranuclear palsy (PSP) and corticobasal degeneration
      (CBD). However, the extent to which the molecular structure of the tau in these
      aggregates is similar or differs between these diseases is unclear. We approached
      this question by examining these disorders with a panel of antibodies that
      represent different structural, conformational, and cleavage-specific tau
      epitopes. Although each of these antibodies reveals AD pathology, they resolved
      into three classes with respect to PSP and CBD: AD2 and Tau-46.1 stained the most
      tau pathology in all cases; Tau-1, 2, 5, and 12 exhibited variable reactivity;
      and Tau-66 and MN423 did not reveal any tau pathology. In addition, hippocampal
      neurofibrillary tangles in these cases showed a predominantly PSP/CBD-like,
      rather than AD-like, staining pattern. These results indicate that the patterns
      of the tau epitopes represented by this panel that reside in the pathological
      aggregates of PSP and CBD are similar to each other but distinct from that of AD.

PMID- 15475685
TI  - Specific differential expression of phospholipase A2 subtypes in rat cerebellum.
AB  - Phospholipase A2 (PLA2) is a family of enzymes playing diverse roles in lipid
      signaling in neurons and glia cells. In this study, we examined the expression of
      subtypes of PLA2 in the cerebellum using immunolabeling and in situ hybridization
      methods. Two Ca2+-dependent cytosolic subtypes (cPLA2alpha and cPLA2beta), one
      Ca2+-independent cytosolic subtype (iPLA2), and two secretory subtypes (sPLA2IIA
      and sPLA2V) were detected in the cerebellum. cPLA2alpha is present in somata and
      dendrites of Purkinje cells, while sPLA2IIA is associated with the endoplasmic
      reticulum in perinuclear regions of Purkinje cell somata. iPLA2 is present in
      granule cells, stellate cells and also in the nucleus of Purkinje cells. In
      addition, cPLA2beta is localized in granule cells, and sPLA2V in Bergmann glia
      cells. These results provide an important basis for identifying functional roles
      of PLA2s in the cerebellum.

PMID- 15475686
TI  - Engraftment and differentiation of neocortical progenitor cells transplanted to
      the embryonic brain in utero.
AB  - Transplantation of neural progenitors or stem cells is a most useful tool to
      investigate the relative contribution of cell-autonomous mechanisms and
      environmental cues in the regulation of cell specification and differentiation
      during CNS development. To assess the capability of neocortical progenitor cells
      to integrate into foreign brain regions, here we examined the fate of precursor
      cells isolated from the dorsal telencephalon of E12 ss-actin-EGFP transgenic
      mouse embryos after heterotopic/heterochronic transplantation to the E16 rat
      brain in utero. Our observations show that donor cells were able to penetrate,
      survive and produce mature cell types into wide regions of the host CNS. Namely,
      EGFP-positive cells acquired site-specific neuronal identities in many
      telencephalic regions, including neocortex, hippocampus, olfactory bulb and
      corpus striatum. In contrast, incorporation into more caudal sites was much less
      efficient. A fraction of donor cells formed large aggregates that remained
      segregated from the host milieu. Such aggregates contained mature neurons and
      glia, including some EGFP-negative elements of host origin, and developed the
      complex organization of the mature nervous tissue. On the other hand,
      transplanted cells that engrafted in the parenchyma of extratelencephalic regions
      predominantly generated glial types. The few neurons failed to acquire obvious
      site-specific phenotypic traits and did not integrate into the local host
      architecture. Altogether, our observations indicate that E12 neocortical
      progenitors are already committed towards regional identities and are unable to
      modify their phenotypic choices when exposed to heterotopic environmental
      conditions along different rostro-caudal domains of the embryonic CNS.

PMID- 15475687
TI  - Vanilloid receptor VR1-positive primary afferents are glutamatergic and contact
      spinal neurons that co-express neurokinin receptor NK1 and glutamate receptors.
AB  - The vanilloid receptor VR1 (TRPV1) is a temperature- and capsaicin-sensitive
      cation channel expressed by a class of primary afferents involved in nociception.
      To confirm the hypothesis that VR1-positive primary afferents are glutamatergic
      and contact spinal neurons that express the main classes of ionotropic glutamate
      receptors, we performed multiple immunofluorescent staining for VR1 and the
      glutamate transporter VGLUT2 (a specific marker for glutamatergic transmission)
      or AMPA and NMDA receptor subunits. VR1-positive cells in the dorsal root
      ganglion and boutons of their central afferent fibers in the dorsal horn
      expressed VGLUT2, and the latter contacted AMPA- or NMDA receptor-positive
      perikarya. Based on our previous observations of preferential targeting of VR1
      positive primary afferents to spinal neurons that express the neurokinin receptor
      NK1 (Hwang et al., 2003), we further quantified the frequency of termination of
      VR1-positive afferents onto NK1-positive neurons co-expressing glutamate
      receptors. A larger fraction of NK1/NMDA receptors-positive than NK1/AMPA
      receptors-positive sites were contacted by VR1-positive boutons. We conclude that
      VR1-positive primary afferents in the rat use glutamate as neurotransmitter and
      contact postsynaptic sites that co-express NK1 and ionotropic glutamate
      receptors.

PMID- 15475688
TI  - Developmental expression of neurotrophin receptor genes in rat geniculate
      ganglion neurons.
AB  - Individual neurons dissected from immunohistochemically stained paraffin sections
      of the developing rat geniculate (VIIth cranial) ganglion were assayed for their
      content of mRNA of the neurotrophin receptor genes, p75 , trkA , trkB and trkC.
      Fetal and postnatal rats, from the 13th embryonic day (E13) until the 20th
      postnatal day (P20), were used. Single cells were subjected to RNA amplification,
      followed by treatment with reverse transcriptase and DNA amplification by the
      polymerase chain reaction (PCR). The identity of the PCR products was verified by
      subcloning and sequencing. A total of 227 neurons were examined, of which 212
      (93%) gave a PCR signal for at least one neurotrophin receptor. We found: (1)
      Approximately half of the neurons expressed more than one receptor. (2) A
      truncated version of trkB , possessing the ligand-binding region but lacking the
      tyrosine kinase domain, occurred quite frequently, often in combination with the
      full-length trkB, with trkA or both. (3) The pattern of staining for trkB-like
      immunoreactivity was usually predictive that either its full length or truncated
      mRNA would be present. This was not the case for trkC-like immunoreactivity.
      Western blots on E15 brain tissue showed no band for full-length trkC (
      approximately 150 kDa), suggesting the antibody may have been immunoreactive with
      a truncated ( approximately 120 kDa) but not a full-length version of the trkC
      receptor. (4) The pattern of neurotrophin receptor gene expression changed during
      development. (5) p75 expression occurred infrequently--in only 7 of the 212
      neurons that gave a signal for any receptor.

PMID- 15475689
TI  - A fourth type of neuroglial cell in the adult central nervous system.
AB  - Labeling central nervous tissue from mature animals with antibodies to NG2
      chondroitin sulfate proteoglycan reveals the existence of large numbers of NG2
      positive cells, at least some of which are oligodendroglial progenitors. It is
      generally agreed that these cells differ from the classically defined neuroglia,
      since they are antigenetically different from astrocytes, oligodendrocytes, or
      microglial cells. Although the NG2 positive cells have been well characterized in
      light microscopic preparations, examination of the labeled cells by electron
      microscopy have not led to general agreement about their morphological features.
      The basic reason for this is that it is difficult to obtain good preservation of
      the fine structure of NG2 labeled neurons. Since these NG2 positive cells are
      abundant in the central nervous system, it was decided to examine routinely
      prepared tissue from the brains of mature monkeys and rats by electron microscopy
      to determine if there is a neuroglial cell type whose presence has been
      overlooked. It soon became evident that there is a fourth type of neuroglial
      cell. These cells have pale, irregular shaped nuclei with a thin rim of
      heterochromatin beneath the nuclear envelope, and they have pale cytoplasm.
      Superficially they resemble astrocytes, which is the probable reason why the
      presence of this fourth type of neuroglial cell has been largely overlooked.
      However, the fourth type of neuroglial cell, here referred to as a ss neuroglial
      cell, has no intermediate filaments in its cytoplasm, the mitochondria are
      thinner than those of astrocytes, centrioles are frequently encountered in their
      cytoplasm, and when they are adjacent to capillaries they are always separated
      from the basal membrane by an astrocytic processes.

PMID- 15475690
TI  - Merkel cells, corpuscular nerve endings and free nerve endings in the mouse
      palatine mucosa express three subtypes of vesicular glutamate transporters.
AB  - The hard palate of rodents is a mucous membrane covered by a keratinized
      epithelium that typically contains Merkel cell (MC)-neurite complexes. MCs have
      engendered considerable research activity because of their involvement in
      mechanoreception and possibly also Merkel cell carcinomas. MCs derive from the
      neural crest, differentiate under control of peripheral nerve factors, are
      enriched in large dense core vesicles, and secrete neuropeptides and other
      neuroactive molecules. Upon stimulation, MC-neurite complexes produce slowly
      adapting type I responses. Here we emphasize that the murine hard palate is a
      highly differentiated sensory region, as shown by intravital staining with a
      styryl dye and immunocytochemistry with antibodies to vesicular glutamate
      transporters (VGLUTs). The entire palate contained densities of sensory endings
      and MC-neurite complexes, that nearly paralleled in abundance the vibrissal pads.
      MCs were differentially distributed in the murine palate; clusters of MCs were
      most abundant in the antemolar and intermolar rugae, while individual MCs were
      particularly enriched in the rugae at the mid-portion of the palate and in the
      postrugal field. VGLUT1, VGLUT2 and VGLUT3 were expressed in MCs throughout,
      although immunostained MCs were most frequently encountered in intermolar than
      antemolar rugae. The same transporters were also present in corpuscular endings
      at the summit of the rugae and in intraepithelial free nerve endings throughout
      the palate. VGLUTs presumably load glutamate into large dense core vesicles in
      MCs and into small clear vesicles in corpuscular and free nerve endings. The data
      suggest that glutamate release, or co-release, is likely to represent an
      important functional aspect of palatine Merkel cells and neighboring corpuscular
      and free nerve endings.

PMID- 15475691
TI  - Dendrite and dendritic spine alterations in Alzheimer models.
AB  - Synaptic damage and loss are factors that affect the degree of dementia
      experienced in Alzheimer disease (AD) patients. Multicolor DiOlistic labeling of
      the hippocampus has been undertaken which allows the full dendritic arbor of
      targeted neurons to be imaged. Using this labeling technique the neuronal
      morphology of two transgenic mouse lines (J20 and APP/PS1) expressing mutant
      forms of the Amyloid Precursor Protein (APP), at various ages, have been
      visualized and compared to Wild Type (WT) littermate controls. Swollen bulbous
      dystrophic neurites with loss of spines were apparent in the transgenic animals.
      Upon quantification, statistically significant reductions in the number of spines
      and total dendrite area was observed in both transgenic mouse lines at 11 months
      of age. Similar morphological abnormalities were seen in human AD hippocampal
      tissue both qualitatively and quantitatively. Immunohistochemistry and DiOlistic
      labeling was combined so that Abeta plaques were imaged in relation to the
      dendritic trees. No preferential localization of these abnormal dystrophic
      neurites was seen in regions with plaques. DiI labeled reative astrocytes were
      often apparent in close proximity to A beta plaques.

PMID- 15475712
TI  - Mixed signals on cell phones and cancer.

PMID- 15475713
TI  - Mobile phone use and the risk of acoustic neuroma.
AB  - BACKGROUND: Radiofrequency exposure from mobile phones is concentrated to the
      tissue closest to the handset, which includes the auditory nerve. If this type of
      exposure increases tumor risk, acoustic neuroma would be a potential concern.
      METHODS: In this population-based case-control study we identified all cases age
      20 to 69 years diagnosed with acoustic neuroma during 1999 to 2002 in certain
      parts of Sweden. Controls were randomly selected from the study base, stratified
      on age, sex, and residential area. Detailed information about mobile phone use
      and other environmental exposures was collected from 148 (93%) cases and 604
      (72%) controls. RESULTS: The overall odds ratio for acoustic neuroma associated
      with regular mobile phone use was 1.0 (95% confidence interval = 0.6-1.5). Ten
      years after the start of mobile phone use the estimates relative risk increased
      to 1.9 (0.9-4.1); when restricting to tumors on the same side of the head as the
      phone was normally used, the relative risk was 3.9 (1.6-9.5). CONCLUSIONS: Our
      findings do not indicate an increased risk of acoustic neuroma related to short
      term mobile phone use after a short latency period. However, our data suggest an
      increased risk of acoustic neuroma associated with mobile phone use of at least
      10 years' duration.

PMID- 15475714
TI  - Environmental tobacco smoke and pregnancy outcome.
AB  - BACKGROUND: Recent reviews conclude that environmental tobacco smoke (ETS) leads
      to diminished birth weight. However, the threshold and magnitude of that effect
      is uncertain. We aimed to determine the magnitude and shape of the relations
      between ETS and various adverse pregnancy outcomes using a highly sensitive
      biochemical assay. METHODS: Maternal serum specimens were collected from more
      than 3000 women enrolled in California's prenatal screening program in 1992 and
      analyzed for cotinine. Information on pregnancy outcomes was obtained from live
      birth/fetal death records and hospital questionnaires. We conducted analyses on
      2777 woman-live birth pairs and 19 woman-fetal death pairs in which the mother
      was presumed to be a nonsmoker (midtrimester cotinine levels < or =10 ng/mL).
      RESULTS: In multiple logistic regression analyses, the odds ratios of fetal
      death, preterm delivery, and term-low birth weight were 3.4, 1.8, and 1.8,
      respectively, in the highest cotinine quintile (0.236-10 ng/mL), compared with
      the lowest quintile (<0.026 ng/mL). In adjusted linear models, there was a linear
      dose-dependent effect of log cotinine on mean birth weight (-109 g) and mean
      infant length (-0.84 cm) over the range of cotinine values. Linear relations were
      not found with respect to infant head circumference or the ratio of brain weight
      to body weight. Infant's body mass index declined with exposures above
      approximately 0.5 ng/mL cotinine. We estimated that ETS levels at or above 0.05
      ng/mL (experienced by 62% of the study population) accounted for 12% of all
      adverse outcomes. CONCLUSIONS: ETS exposure in pregnant women adversely affects
      pregnancy by increasing fetal mortality and preterm delivery at higher exposure
      levels and slowing fetal growth across all levels of ETS exposure.

PMID- 15475715
TI  - Smoking and the risk of oral clefts: exploring the impact of study designs.
AB  - BACKGROUND: Maternal cigarette smoking is a suspected cause of oral clefts,
      although this association has not been firmly established. We used case
      crossover, case-time-control, and bidirectional case-crossover designs to
      supplement findings from a case-control study of maternal smoking and oral clefts
      among offspring in a large birth registry. METHODS: Data are from the Swedish
      Medical Birth Registry. From 1983 through 1997 there were 678 recorded cases of
      cleft palate and 1175 cases of cleft lip with or without palate. Maternal smoking
      status was ascertained in early pregnancy. Controls for the case-control study
      were a random sample of infants born without a cleft; controls for the case
      crossover designs were nonmalformed infants born to case mothers. RESULTS: Cleft
      palate was positively associated with maternal smoking in all study designs,
      whereas cleft lip with or without cleft palate was associated with smoking only
      in the case-control design. In the case-control design, the odds ratios for cleft
      palate were 1.2 (95% confidence interval = 1.0-1.5) for women who smoked 1 to 9
      cigarettes per day and 1.4 (1.1-1.8) for women who smoked 10+ cigarettes per day.
      In the case-time-control analysis, the odds ratio for cleft palate with maternal
      smoking was 3.2 (1.3-7.4) and in the bidirectional case-crossover design, the
      odds ratio was 2.2 (1.1-4.1). CONCLUSIONS: An association between smoking and
      cleft palate was supported by all designs, whereas that between smoking and cleft
      lip with or without cleft palate was not. Case-only designs are a viable option
      in birth registries and may yield more information than a case-control design
      alone.

PMID- 15475716
TI  - Disparities in birth outcomes by neighborhood income: temporal trends in rural
      and urban areas, british columbia.
AB  - BACKGROUND: Knowledge of socioeconomic disparities in health is of interest to
      both the general public and public health policymakers. It is unclear how
      disparities in birth outcomes by socioeconomic status have changed over time,
      particularly in settings with universal health insurance and favorable
      socioeconomic conditions. METHODS: We identified a cohort of all births (n =
      713,950) registered in British Columbia, 1985-2000. We compared rates and
      relative risks (RRs) of preterm birth, small-for-gestational-age (SGA),
      stillbirth, and neonatal and postneonatal death across neighborhood-income
      quintiles from Q1 (richest, the reference) to Q5 (poorest) by 4-year intervals in
      rural and urban areas. Logistic regression was used to control for maternal and
      pregnancy characteristics. RESULTS: Maternal characteristics varied widely across
      neighborhood-income quintiles in both rural and urban areas. There were moderate
      and persistent disparities in birth outcomes across neighborhood-income quintiles
      in urban but not rural areas. The relative disparities in urban areas did not
      diminish over time for all birth outcomes and actually rose for postneonatal
      mortality. For example, crude RRs (95% confidence intervals) for Q5 versus Q1 in
      urban areas for SGA were 1.44 (1.37-1.52) in 1985-1988 and 1.41 (1.33-1.49) in
      1997-2000; for postneonatal death, the corresponding results were 1.61 (1.17
      2.20) and 2.20 (1.24-3.92), respectively. Most of the observed disparities could
      not be explained by observed maternal and pregnancy characteristics. CONCLUSION:
      Moderate disparities in birth outcomes by neighborhood income persist in urban
      areas (although not rural areas) of British Columbia, despite a universal health
      insurance system and generally favorable socioeconomic conditions.

PMID- 15475717
TI  - Occupational exposure to electromagnetic fields and risk of Alzheimer's disease.
AB  - BACKGROUND: Extremely-low-frequency magnetic field (ELF-MF) exposure is suspected
      to increase the risk of Alzheimer's disease. Such fields are present in the
      vicinity of electrical motors and other electric appliances containing coils.
      METHODS: We investigated lifetime occupational ELF-MF exposure in relation to
      Alzheimer's disease and dementia among a community dementia-free cohort (n = 931)
      age 75 years and older in Stockholm, Sweden. This cohort was followed from 1987
      1989 until 1994-1996 to detect dementia cases (Diagnostic and Statistical Manual
      of Mental Disorders, revised 3rd edition criteria). Information on lifetime job
      history was obtained by interview, usually of next of kin. ELF-MF exposure was
      assessed using a job-exposure matrix, measurement on historical equipment, and
      expert estimation. We analyzed the data with Cox models controlling for potential
      confounders. RESULTS: Dementia was diagnosed in 265 subjects, including 202 with
      Alzheimer's disease. Among men, ELF-MF exposure > or=0.2 microT in lifetime
      principal job was related to multivariate-adjusted relative risks of 2.3 (95% CI
      = 1.0-5.1) for Alzheimer's disease and 2.0 (1.1-3.7) for dementia. We found no
      association among women. A similar sex-specific pattern was seen for the
      associations with average ELF-MF exposure throughout the work life. A dose
      response relation was suggested in men, with multivariate-adjusted relative risks
      of 2.4 (0.8-6.8) for Alzheimer's disease and 2.5 (1.1-5.6) for dementia for the
      upper tertile of lifetime average exposure. CONCLUSIONS: Long-term occupational
      exposure to a higher ELF-MF level may increase the risk of Alzheimer's disease
      and dementia in men. Similar patterns were not seen in women, which may in part
      be the result of a greater exposure misclassification in women than in men.

PMID- 15475718
TI  - Is chronic airway obstruction from cotton dust exposure reversible?
AB  - BACKGROUND: Exposure to cotton dust is known to cause chronic airway obstruction,
      but there is little information on whether the obstructive impairment is
      reversible after the exposure stops. METHODS: Longitudinal changes in lung
      function were evaluated among 429 cotton textile workers and 449 silk workers in
      Shanghai, China, beginning in 1981. Both active and retired workers were tested
      every 4 to 6 years for 15 years. RESULTS: Overall, cotton workers had greater
      annual declines in forced expiratory volume in 1 second (FEV1) and forced vital
      capacity (FVC). Compared with active workers, retired cotton workers had lower
      annual loss of FEV1, although the retired workers had a greater loss during their
      active employment than the currently active workers. No such trends were detected
      in silk workers. Annual declines in FEV1 in retired cotton workers were smaller
      with increasing time since retirement. Multivariate analysis showed that
      retirement was a substantial contributing factor for improved FEV1 and FVC in the
      cotton workers, especially among those who did not smoke. Correspondingly,
      remission of airflow obstruction, defined as a ratio of FEV1 and FVC of less than
      70%, was more common in retirees than in the active workers, and more common in
      nonsmokers than in smokers. CONCLUSION: Chronic airway obstruction related to
      long-term exposure to cotton dust may be partially reversible after the exposure
      ceases, although lung function does not return to the level found in unexposed
      workers.

PMID- 15475719
TI  - Fine particulate matter and wheezing illnesses in the first year of life.
AB  - BACKGROUND: Recent evidence implicates fine particulate matter (PM2.5),
      principally from vehicular exhaust, as a major cause of increased mortality and
      morbidity. However, there are limited data on the impact of PM2.5 on infant
      respiratory illnesses. METHODS: We conducted a cohort study of 504 infants
      recruited at 4 months of age from primary health care units in southeastern
      Santiago, Chile. Project physicians followed infants through the first year of
      life via monthly check-ups and by appointments on demand. We obtained data for
      fine particulate matter, sulfur dioxide (SO2), and nitrogen dioxide (NO2) from
      the governmental monitoring network. RESULTS: The most frequent diagnosis during
      follow-up was wheezing bronchitis, occurring 19.5 times per 100 infants per
      month. After adjusting for sex, socioeconomic level, family history of asthma,
      minimum temperature, and number of older siblings, we found that an increase of
      10 microg/m of PM2.5 24-hour average was related to a 5% increase (95% confidence
      interval 0-9%) in the risk for wheezing bronchitis (1-day lag). This association
      was present for different lags, with a maximum observed for a 9-day lag (9%; 6
      12%). No consistent association was detected with NO2 or SO2 ambient levels.
      Lower socioeconomic status and having older siblings were also associated with
      the risk of wheezing bronchitis. The association of PM2.5 and wheezing bronchitis
      was stronger among infants with a family history of asthma than among infants
      without. CONCLUSIONS: Air pollution in the form of fine particulates, mostly from
      vehicular exhaust, may adversely affect infants' respiratory health with
      potential for chronic effects later in life.

PMID- 15475720
TI  - Indoor radon and lung cancer in France.
AB  - BACKGROUND: Several case-control studies have indicated an increased risk of lung
      cancer linked to indoor radon exposure; others have not supported this
      hypothesis, partly because of a lack of statistical power. As part of a large
      European project, a hospital-based case-control study was carried out in 4 areas
      in France with relatively high radon levels. METHODS: Radon concentrations were
      measured in dwellings that had been occupied by the study subjects during the 5-
      to 30-year period before the interview. Measurements of radon concentrations were
      performed during a 6-month period using 2 Kodalpha LR 115 detectors (Dosirad,
      France), 1 in the living room and 1 in the bedroom. We examined lung cancer risk
      in relation to indoor radon exposure after adjustment for age, sex, region,
      cigarette smoking, and occupational exposure. RESULTS: We included in the
      analysis 486 cases and 984 controls with radon measures in at least 1 dwelling.
      When lung cancer risk was examined in relation to the time-weighted average radon
      concentration during the 5- to 30-year period, the estimated relative risks (with
      95% confidence intervals) were: 0.85 (0.59-1.22), 1.19 (0.81-1.77), 1.04 (0.64
      1.67), and 1.11 (0.59-2.09) for categories 50-100, 100-200, 200-400, and 400+
      becquerels per cubic meter (Bq/m), respectively (reference <50 Bq/m). The
      estimated relative risk per 100 Bq/m was 1.04 (0.99-1.11) for all subjects and
      1.07 (1.00-1.14) for subjects with complete measurements. CONCLUSIONS: Our
      results support the presence of a small excess lung cancer risk associated with
      indoor radon exposure after precise adjustment on smoking. They are in agreement
      with results from some other indoor radon case-control studies and with
      extrapolations from studies of underground miners.

PMID- 15475721
TI  - Parental age, family size, and risk of multiple sclerosis.
AB  - BACKGROUND: Family structure, such as having siblings, provides proxy measures
      for a variety of characteristics relevant to disease risk. The etiology of
      multiple sclerosis (MS) is not well defined and analysis of family structure may
      provide etiologic clues. We conducted a case-control study to examine possible
      associations. METHODS: Using the Swedish Inpatient Register, we identified 4443
      patients with a diagnosis of MS. From the general Swedish population, using birth
      and death registers, we selected 24,194 controls with similar characteristics for
      year, county of birth, and survival until at least age at diagnosis of the
      matched cases. The Multi-Generation Register linked data on siblings and parents.
      The Census provided father's social class based on occupation. RESULTS: Having 3
      or more younger siblings, compared with none, produced an adjusted odds ratio
      (OR) for MS (with 95% confidence interval) of 0.80 (0.70-0.92) (adjusting for
      number of siblings, twins, maternal and paternal age, parental MS, sex, father's
      social class, county and year of birth). With 3 or more older siblings, the
      adjusted OR was 0.83 (0.72-0.96). Different-sex twin pairs compared with
      singletons had an OR of 0.59 (0.37-0.95) for MS. The risk of MS increased
      steadily with father's age but not mother's age, up to 2.00 (1.35-2.96) for 51-
      to 55-year-old fathers (compared with 21- to 25-year-old fathers). CONCLUSIONS:
      Parents who have offspring with MS may have subtly impaired fertility. The
      unexpected association with paternal age may be the result of an increased risk
      of accumulating germ cell mutations among older men.

PMID- 15475722
TI  - Methods for the analysis of continuous biomarker assay data with increased
      sensitivity.
AB  - Prospective studies must be able to adapt to improved technology and adopt new
      assays with increased limits of detection. Our objective is to describe methods
      for incorporating new technologies in which the lower limits of quantification of
      a biomarker are enhanced. One may conduct an analysis of data with new and old
      sensitivity levels using a variety of methods, including retesting a sample of
      stored specimens from which multiple imputation may be applied, and a parametric
      approach that accounts for the changing limit of detection. We compare these
      methods in terms of their statistical bias and efficiency and identify the
      conditions under which the various methods perform well and then demonstrate our
      methods by evaluating differences in HIV RNA levels obtained from 2 prospective
      cohort studies.

PMID- 15475723
TI  - Weight change and the risk of gestational diabetes in obese women.
AB  - BACKGROUND: Obesity is an established risk factor for gestational diabetes. It is
      not known whether this risk might be reduced through weight loss between
      pregnancies. We sought to determine whether weight loss between pregnancies
      reduced the risk of gestational diabetes among obese women. METHODS: We conducted
      a population-based cohort study of 4102 women with 2 or more singleton live
      births in Washington State between 1992 and 1998. All subjects were nondiabetic
      and obese (at least 200 lbs) at their first birth during these years. Weight
      change was calculated as the difference between prepregnancy weight for the 2
      pregnancies. We estimated relative risks of gestational diabetes at the
      subsequent delivery through stratified analyses and Mantel-Haenszel estimates.
      RESULTS: Thirty-two percent of women lost weight between pregnancies, with a mean
      weight loss of 23 lbs. Women who lost at least 10 lbs between pregnancies had a
      decreased risk of gestational diabetes relative to women whose weight changed by
      less than 10 lbs (relative risk = 0.63; 95% confidence interval = 0.38-1.02,
      adjusted for age and weight gain during each pregnancy). Of the 61% of women who
      gained weight between pregnancies, the mean weight gain was 22 lbs. Women who
      gained at least 10 lbs had an increased risk of gestational diabetes (1.47; 1.05
      2.04). CONCLUSIONS: Even moderate changes in prepregnancy weight can apparently
      affect the risk of gestational diabetes among obese women. This may offer further
      motivation for interventions aimed at reducing obesity among women of
      reproductive age.

PMID- 15475724
TI  - On the importance of using multiple methods of dietary assessment.
AB  - BACKGROUND: Plasma carotenoid concentrations reflect intake of vegetables and
      fruits, the major food sources of these compounds. This study compared the
      ability of 2 measures of dietary intake (24-hour diet recalls and food frequency
      questionnaires [FFQs]) to corroborate plasma carotenoid concentrations in a
      subset of women participating in a diet intervention trial. METHODS: Plasma
      carotenoid concentrations and dietary intakes, estimated from 24-hour diet
      recalls and FFQs, were examined at baseline and 1 year later in a subset of 395
      study participants (197 intervention and 198 comparison group). We used
      longitudinal models to examine associations between estimated intakes and plasma
      carotenoid concentrations. These analyses were stratified by study group and
      adjusted for body mass index (BMI), plasma cholesterol concentration, and total
      energy intake. We conducted simulations to compare mean-squared errors of
      prediction of each assessment method. RESULTS: In mixed-effects models, the
      estimated carotenoid intakes from both dietary assessment methods were strongly
      associated with plasma concentrations of alpha-carotene, beta-carotene, and
      lutein. Furthermore, modeling the 2 sources of intake information as joint
      predictors reduced the prediction error. CONCLUSION: These findings underscore
      the importance of using multiple measures of dietary assessment in studies
      examining diet-disease associations.

PMID- 15475725
TI  - Regional variations in breast cancer among california teachers.
AB  - BACKGROUND: Observed regional differences in breast cancer incidence could
      provide valuable clues to the etiology of this disease. The pattern of
      historically higher breast cancer rates among residents of California's San
      Francisco Bay and Southern Coastal areas is evident in the disease experience
      among members of the California Teachers Study. This large cohort study has
      followed female professional school employees for cancer incidence since 1995 and
      has collected extensive information on breast cancer risk factors. METHODS:
      Between 1996 and 1999, invasive breast cancer was diagnosed in 1562 of the
      115,611 cohort members who could be geocoded to a California address in 1995 and
      who had no previous breast cancer diagnosis. Adjusted hazard rate ratios (HRs)
      were estimated through multivariate Cox proportional hazards modeling. RESULTS:
      Rates were higher for cohort members in the San Francisco Bay area (HR = 1.22;
      95% confidence interval = 1.06-1.40) and Southern Coastal area (1.16; 1.04-1.30)
      compared with those in the rest of California. The distributions of variables
      representing socioeconomic status, urbanization, and personal risk factors were
      consistent with higher risks for cohort members residing in the San Francisco Bay
      and Southern Coastal areas. Adjustment for these factors, however, did not
      explain regional differences in incidence, resulting in HRs that remained
      elevated for these 2 areas. CONCLUSION: Regional differences in breast cancer
      incidence in this large, well-defined cohort are not easily explained by known
      risk factors.

PMID- 15475726
TI  - Hospital admissions for heart disease: the effects of temperature and humidity.
AB  - BACKGROUND: We estimated the effects of temperature and humidity on hospital
      admissions for heart disease (International Classification of Diseases, 9th
      revision [ICD-9] codes 390-429) and myocardial infarction (ICD-9 code 410) of
      persons age 65 and older in 12 U.S. cities with a wide range of climates. To
      account for possible delayed effects and harvesting, we examined the impact of
      weather up to 20 days before each admission. METHODS: Poisson regression models
      were fitted in each city, with regression splines used to control for season and
      barometric pressure. We also controlled day of the week. We estimated the effect
      and the lag structure of both temperature and humidity based on a distributed lag
      model. FINDINGS: For cities in both hot and cold climates, we found that hospital
      admissions for all heart disease increased monotonically with average temperature
      on the same day as and the day before admission. The effect of very high
      temperatures had a temporal pattern consistent with harvesting: several days
      after an episode of high temperature, there were fewer admissions. In contrast, a
      protective effect of cold temperature persisted without rebound. The effects of
      either hot or cold temperature disappeared within 10 days of exposure. There was
      no evidence for a humidity effect. Similar but smaller effects of temperature
      were seen for admissions for myocardial infarction specifically. CONCLUSIONS: The
      effects of temperature on hospital admissions predominantly occur within a few
      days after exposure, and much of the effect of hot temperatures is short-term
      displacement of events.

PMID- 15475727
TI  - Emotional stress and traffic accidents: the impact of separation and divorce.
AB  - BACKGROUND: Personal responses to stressful life events are suspected of
      increasing the risk of serious traffic accidents. METHODS: We analyzed data from
      a French cohort study (the GAZEL cohort), including a retrospective driving
      behavior questionnaire, from 13,915 participants (10,542 men age 52-62 years and
      3373 women age 47-62 years in 2001). Follow-up data covered 1993-2000. Hazard
      ratios for serious accidents (n = 713) were computed by Cox's proportional hazard
      regression with time-dependent covariates. Separate analyses were also performed
      to consider only at-fault accidents. RESULTS: Marital separation or divorce was
      associated with an increased risk of a serious accident (all serious accidents:
      hazard ratio 2.9, 95% confidence interval = 1.7-5.0; at-fault accidents: 4.4, 2.3
      8.3). The impact of separation and divorce did not differ according to alcohol
      consumption levels. Other life events associated with increased risk of serious
      accident were a child leaving home (all accidents: 1.2, 0.97-1.6; at-fault
      accidents: 1.5, 1.1-2.1), an important purchase (all accidents: 1.4, 1.1-1.7; at
      fault accidents: 1.6, 1.2-2.1), and hospitalization of the partner (all
      accidents: 1.4, 1.1-2.0). CONCLUSION: This study suggests that recent separation
      and divorce are associated with an increase in serious traffic accidents.

PMID- 15475728
TI  - Alcohol consumption and acute myocardial infarction: a benefit of alcohol
      consumed with meals?
AB  - BACKGROUND: The apparent favorable effect of alcohol on the risk of acute
      myocardial infarction (MI) may be related to its hypoinsulinemic effect when
      consumed with meals. We studied how the timing of alcohol consumption in relation
      to meals might affect the risk of MI in a population with relatively high regular
      alcohol consumption. METHODS: We conducted a case-control study between 1995 and
      1999 in Milan, Italy. Cases were 507 subjects with a first episode of nonfatal
      acute MI, and controls were 478 patients admitted to hospitals for other acute
      diseases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by
      multiple logistic regression models. RESULTS: Compared with nondrinkers, an
      inverse trend in risk was observed when alcohol was consumed during meals only
      (for > or =3 drinks per day: OR = 0.50; 95% CI = 0.30-0.82). In contrast, no
      consistent trend in risk was found for subjects drinking outside of meals (for >
      or =3 drinks per day: 0.98; 0.49-1.96). The pattern of risk was similar when we
      considered people who drank only wine. CONCLUSIONS: Alcohol drinking during meals
      was inversely related with risk of acute MI, whereas alcohol drinking outside
      meals only was unrelated to risk.

PMID- 15475729
TI  - A conversation with Jerry Morris. Interview by George Davey Smith.

PMID- 15475730
TI  - Maternal/newborn GSTT1 null genotype contributes to risk of preterm, low
      birthweight infants.
AB  - OBJECTIVES: Maternal cigarette smoke exposure during pregnancy has been
      identified as a risk factor for prematurity and low birthweight. However, little
      is known about genetic susceptibility and possible interactions with cigarette
      smoking which may increase risk of these events. METHODS: Maternal peripheral and
      umbilical cord blood samples from 955 mother/newborn pairs were genotyped for a
      panel of phase I/II metabolic enzymes responsible for the metabolism of tobacco
      related mutagens and carcinogens in order to evaluate the association with
      premature birth. RESULTS: As reported previously, maternal cigarette smoking
      during the last trimester was significantly associated with premature birth. In
      addition, maternal glutathione S-transferase T1 (GSTT1) null genotype also
      increased risk of premature birth. Risk was further elevated among subjects with
      the combination of maternal and newborn GSTT1 null genotype with or without
      maternal cigarette smoke. CONCLUSIONS: These observations suggest that women
      and/or newborns with the GSTT1 null genotype who are exposed to cigarette smoke
      during pregnancy are at elevated risk for premature delivery. The ability to
      identify high-risk women by genotyping has potential for reducing the frequency
      of premature births, a major public health concern.

PMID- 15475731
TI  - Extracting and characterizing gene-drug relationships from the literature.
AB  - A fundamental task of pharmacogenetics is to collect and classify relationships
      between genes and drugs. Currently, this useful information has not been
      comprehensively aggregated in any database and remains scattered throughout the
      published literature. Although there are efforts to collect this information
      manually, they are limited by the size of the published literature on gene-drug
      relationships. Therefore, we investigated computational methods to extract and
      characterize pharmacogenetic relationships between genes and drugs from the
      literature. We first evaluated the effectiveness of the co-occurrence method in
      identifying related genes and drugs. We then used supervised machine learning
      algorithms to classify the relationships between genes and drugs from the
      Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB) into five
      categories that have been defined by active pharmacogenetic researchers as
      relevant to their work. The final co-occurrence algorithm was able to extract 78%
      of the related genes and drugs that were published in a review article from the
      literature. Our algorithm subsequently classified the relationships between genes
      and drugs from the PharmGKB into five categories with 74% accuracy. We have made
      the data available on a supplementary website at
      http://bionlp.stanford.edu/genedrug/ Gene-drug relationships can be accurately
      extracted from text and classified into categories. Although the relationships
      that we have identified do not capture the details and fine distinctions often
      made in the literature, these methods will help scientists to track the ever
      growing literature and create information resources to support future
      discoveries.

PMID- 15475732
TI  - The effect of rare human sequence variants on the function of vesicular monoamine
      transporter 2.
AB  - The extent to which genetic variation in a population contributes to phenotypic
      variation depends on the frequency of sequence polymorphisms and the effect of
      these polymorphisms on function. The frequency of polymorphisms might also
      reflect the severity of their effects on function. We therefore examined the
      effect of very rare single nucleotide polymorphisms (SNPs) on the activity of the
      vesicular monoamine transporter 2 (VMAT2, SLC18A2), a gene implicated in
      neuropsychiatric disease. Of the two rare SNPs identified in an ethnically
      diverse population, neither eliminates transport, but one that involves
      replacement of a highly conserved residue with a very similar amino acid impairs
      substrate recognition. This variant, and another affecting an unconserved
      residue, also affect inhibition by the clinically used drug reserpine. Because
      VMAT2 influences a form of toxicity similar to Parkinson's disease, we extended
      the analysis to two SNPs identified in a population with Parkinson's disease.
      These two SNPs have no detectable effect on most aspects of VMAT2 function, but
      one that affects a highly conserved residue may increase sensitivity to the
      inhibitor tetrabenazine. The results illustrate the relationship between
      conservation of the affected residue, the nature of the substitution and effects
      on substrate versus inhibitor interaction.

PMID- 15475733
TI  - Determination and analysis of single nucleotide polymorphisms and haplotype
      structure of the human carboxylesterase 2 gene.
AB  - Carboxylesterases are members of the serine esterase super family important in
      the metabolism of a wide variety of substrates, including xenobiotics and
      prodrugs. There are two known carboxylesterases expressed in human liver, small
      intestine and other tissues, carboxylesterase 1 (CES1) and carboxylesterase 2
      (CES2). The aim of this study was to identify polymorphisms in the CES2 gene and
      determine whether these polymorphisms affect expression levels of CES2 or rate of
      metabolism of irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy
      camptothecin). Microsome samples prepared from liver tissues of 78 normal
      individuals were used to determine the rate of hydrolysis of irinotecan and
      procaine (an anaesthetic hydrolysed by CES2 but not CES1). The rate of hydrolysis
      of irinotecan is highly variable among individuals, ranging from 2.7-138 pmol/mg
      protein/h (mean +/- SD 26.0 +/- 22.9). Fifteen single nucleotide polymorphisms
      (SNPs) were identified, one is in an exon, 9 are in introns, three are in the 3'
      untranslated region (UTR), and two are in the 5'-flanking region. Eight of the 15
      SNP loci have rare allele frequencies greater than 5%, of which three were
      greater than 20%. Genotyping of samples from the SNP Consortium demonstrated
      different distributions among African-Americans, Asian-Americans and European
      Americans. We also analysed the haplotype structure and estimated linkage
      disequilibrium (LD). A SNP located in the 5'-UTR (5'-UTR-363) was found in LD
      with loci in intron 1 (Intron1 + 947, Intron1 + 1361, Intron1 + 1643). Haplotypes
      with homozygous rare alleles on these loci exhibit lower mRNA levels as
      determined by real time polymerase chain reaction (P < 0.01) and the
      incorporation of rare alleles in haplotypes correlate with reduced mRNA (P =
      0.03). The 5'-UTR-363 SNP is located in one of the three promoters of CES2.
      However, we did not observe significant differences in CES2 activities
      (irinotecan and procaine hydrolysis) among individuals with different haplotypes.

PMID- 15475734
TI  - Pharmacogenetics of selective serotonin reuptake inhibitor response: a 6-month
      follow-up.
AB  - BACKGROUND: We previously reported the association between some genetic factors
      and short-term antidepressant outcome. In the present paper we investigated the
      same gene variants in a prospective 6-months naturalistic follow-up. METHODS: The
      sample included 185 inpatients affected by recurrent major depression
      consecutively admitted to the Psychiatric Inpatient Unit of San Raffaele Hospital
      from 1998 to 2003 and prospectively followed for 6 months after their recovery.
      All the patients were undertaking continuation therapy. The functional
      polymorphism in the upstream regulatory region of the serotonin transporter gene
      (SERTPR), the tryptophan hydroxylase A218C substitution, a VNTR polymorphism
      located 1.2 kb upstream of the monoamine oxidase-A coding sequences, the CLOCK
      gene T3111C and the PER3exon15 gene T1940G substitutions were analysed, using PCR
      based techniques. RESULTS: No association was found between clinical variables
      and relapses; subjects showing TT genotype at CLOCK gene tended to relapse within
      6 months after recovery more than TC and CC subjects taken together. A non
      significant tendency of SERTPR*s/s subjects to a minor frequency of relapse was
      also observed. CONCLUSION: Some subjects showing remission after acute treatment
      relapsed within 6 months, despite undertaking a maintenance treatment; the causes
      could be heterogeneous, but CLOCK gene variants may influence the outcome.

PMID- 15475735
TI  - Ethnic variation in CYP2A6 and association of genetically slow nicotine
      metabolism and smoking in adult Caucasians.
AB  - Genetically variable CYP2A6 is the primary enzyme that inactivates nicotine to
      cotinine. Our objective was to investigate allele frequencies among five ethnic
      groups and to investigate the relationship between genetically slow nicotine
      metabolic inactivation and smoking status, cigarette consumption, age of first
      smoking and duration of smoking. Chinese, Japanese, Canadian Native Indian,
      African-North American and Caucasian DNA samples were assessed for CYP2A6 allelic
      frequencies (CYP2A6*1B-*12,*1x2). Adult Caucasian non-smokers (n = 224) (1-99
      cigarettes/lifetime) and smokers (n = 375) (> or = 100 cigarettes/lifetime) were
      assessed for demographics, tobacco/drug use history and DSM-IV dependence and
      genotyped for CYP2A6 alleles associated with decreased nicotine metabolism
      (CYP2A6*2, CYP2A6*4, CYP2A6*9, CYP2A6*12). CYP2A6 allele frequencies varied
      substantially among the ethnic groups. The proportion of Caucasian slow nicotine
      inactivators was significantly lower in current, DSM-IV dependent smokers
      compared to non-smokers [7.0% and 12.5%, respectively, P = 0.03, odds ratio (OR)
      = 0.52; 95% confidence interval (CI) 0.29-0.95]; non-dependent smokers showed
      similar results. Daily cigarette consumption (cigarettes/day) was significantly
      (P = 0.003) lower for slow (21.3; 95% CI 17.4-25.2) compared to normal
      inactivators (28.2; 95% CI 26.4-29.9); this was observed only in DSM-IV dependent
      smokers. Slow inactivators had a significantly (P = 0.03) lower age of first
      smoking compared to normal inactivators (13.0 years of age; 95% CI 12.1-14.0
      versus 14.2; 95% CI 13.8-14.6), and a trend towards smoking for a shorter
      duration. This study demonstrates that slow nicotine inactivators are less likely
      to be adult smokers (dependent or non-dependent). Slow inactivators also smoked
      fewer cigarettes per day and had an earlier age of first smoking (only dependent
      smokers).

PMID- 15475736
TI  - A coding polymorphism in the CYSLT2 receptor with reduced affinity to LTD4 is
      associated with asthma.
AB  - BACKGROUND: Cysteinyl leukotrienes (CYSLTR) are potent biological mediators in
      the pathophysiology of asthma for which two receptors have been characterized,
      CYSLTR1 and CYSLTR2. The leukotriene modifying agents currently used to control
      bronchoconstriction and inflammation in asthmatic patients are CYSLTR1-specific
      leukotriene receptor antagonists. In this report, we investigated a possible role
      for therapeutic modulation of CYSLTR2 in asthma by investigating genetic
      association with asthma and further characterization of the pharmacology of a
      coding polymorphism. METHODS: The association of CYSLTR2 polymorphisms with
      asthma was assessed by transmission disequilibrium test in two family-based
      collections (359 families from Denmark and Minnesota, USA and 384 families from
      the Genetics of Asthma International Network). RESULTS: A significant association
      of the coding polymorphism, 601A>G, with asthma was observed (P = 0.003). We
      replicated these findings in a collection of 384 families from the Genetics of
      Asthma International Network (P = 0.04). The G allele is significantly under
      transmitted to asthmatics, indicating a possible role for this receptor in
      resistance to asthma. The potency of cysteinyl leukotrienes at the wild-type
      CYSLTR2 and the coding polymorphism 601A>G were assessed using a calcium
      mobilization assay. The potency of LTC4 and LTE4 was similar for both forms of
      the receptor and LTB4 was inactive, however, LTD4 was approximately five-fold
      less potent on 601A>G compared to wild-type CYSLTR2. CONCLUSIONS: Since 601A>G
      alters the potency of LTD4 and this variant allele may be associated with
      resistance to asthma, it is possible that modulation of the CYSLTR2 may be useful
      in asthma pharmacotherapy.

PMID- 15475739
TI  - A pilot study of adalimumab in infliximab-allergic patients.
AB  - The anti-TNF-alpha antibody infliximab (Remicade) is highly effective in the
      treatment of Crohn's disease. A subset of patients experience allergic reactions
      as a result of antibodies to infliximab (ATIs). The purpose of the current study
      is to describe the safety and efficacy of adalimumab (Humira) in patients
      previously allergic or intolerant to infliximab. Adalimumab is an anti-TNF-alpha
      agent containing only human peptide sequences. Seven patients have been treated
      with adalimumab who had experienced immediate- or delayed-hypersensitivity
      reactions to infliximab and one with infliximab-induced lupus. Except for
      injection site discomfort, adalimumab was well tolerated without signs or
      symptoms of allergic reactions. One patient who had previously received pooled
      human immunoglobulin developed a pruritic rash after each dose of adalimumab.
      Patients with active disease who had previously experienced a robust response to
      infliximab responded to adalimumab as reflected by an improvement in Harvey
      Bradshaw index and inflammatory markers. Based on these preliminary data,
      adalimumab may be a safe and effective substitute for infliximab-allergic
      patients. Individuals who have been exposed to human antibodies may be sensitized
      to other human antibodies such as adalimumab.

PMID- 15475740
TI  - Indicators of clinical response to treatment with six-mercaptopurine or
      azathioprine in patients with inflammatory bowel disease.
AB  - OBJECTIVES: There is some uncertainty regarding how to best dose and
      therapeutically monitor 6-mercaptopurine or azathioprine in patients with
      inflammatory bowel disease. The purpose of this study was to assess the relation
      between clinical response, 6-mercaptopurine metabolite levels, relative
      leukopenia, and drug dose. METHODS: 60 patients with inflammatory bowel disease
      who were on stable doses of 6-mercaptopurine or azathioprine for > or = 3 months
      and who had measurements of 6-mercaptopurine metabolite levels were evaluated.
      Patients were classified as complete responders (N = 24), partial responders (N =
      7), or non-responders (N = 29). RESULTS: Drug dose was associated with clinical
      response when we analyzed adjusted doses based on molecular drug weight (P =
      0.002). 6-Thioguanine levels also were associated with clinical response (P =
      0.003) and the maximal difference between responders and non-responders was seen
      at 6-thioguanine levels greater than 260 pmol/8 x 10(8) RBC. Relative leukopenia,
      defined as white blood cell count less than either 5.0 or 4.0 K/uL, was not
      associated with clinical response (P = 0.13 and 0.77 respectively). CONCLUSIONS:
      1. Drug dose and 6-thioguanine levels are related to clinical response in
      patients with inflammatory bowel disease on 6-mercaptopurine or azathioprine. 2.
      For 6-thioguanine levels, there is a fair amount of overlap, but maximal
      differentiation between responders and non-responders is seen at levels > 260
      pmol/8 x 10(8) RBC. 3. Relative leukopenia does not correlate well with clinical
      response.

PMID- 15475741
TI  - Smoking and immunomodulators do not influence the response or duration of
      response to infliximab in Crohn's disease.
AB  - OBJECTIVE: Clinical predictors for infliximab response are still unknown.
      Identifying predictors of response to infliximab in Crohn's disease may improve
      our selection of patients. METHODS: Two hundred patients with luminal (61%) or
      fistulous (39%) Crohn's disease and at least 6 months of follow-up following a
      total of 416 infliximab infusions were evaluated. Clinical response and duration
      of response were the primary endpoints. RESULTS: Patients with fistulous disease
      had a higher response rate (83% versus 70%, P = 0.044) and a significantly longer
      duration of response compared with patients with luminal disease (17.4 versus
      10.1 wks, P = 0.017). For luminal disease, nonsmokers and smokers had similar
      response rates (74% versus 64%, P = 0.5) and similar durations of response (9.4
      wks versus 8.4 wks P = 0.6) while patients taking concurrent immunomodulators had
      similar response rates compared with those not taking immunomodulators (74%
      versus 71%, P = 0.9) and similar durations of response (10.4 wks versus 10.6 wks,
      P = 0.9). For fistulous disease, response rates (89% versus 83% P = 0.9) and
      duration of response (16.9 wks versus 10.1 wks, P = 0.10) were similar between
      nonsmokers and smokers and concurrent immunomodulators had no effect on response
      (89% versus 86%, P = 0.9) or duration of response (19.8 wks versus 15.4 wks, P =
      0.46). Multivariable analysis confirmed that neither smoking, corticosteroids,
      immunomodulator therapy, gender, age, age of disease onset, disease duration, nor
      luminal disease location significantly influenced response or duration of
      response. CONCLUSIONS: Patients with fistulous disease had a higher response rate
      and a significantly longer duration of response compared with patients with
      luminal disease. However, among patients with luminal or fistulous disease,
      neither smoking nor immunomodulators had any effect on response or duration of
      response.

PMID- 15475742
TI  - The spectrum of gastrointestinal toxicity and effect on disease activity of
      selective cyclooxygenase-2 inhibitors in patients with inflammatory bowel
      disease.
AB  - The safety and toxicity associated with the use of selective cyclooxygenase-2
      (COX-2) inhibitors in patients with inflammatory bowel disease (IBD) has not been
      extensively studied. Thirty-three patients with IBD who were prescribed celecoxib
      or rofecoxib were identified from questionnaire during their clinic visit at the
      Cedars-Sinai IBD Center between 1999 and 2002. Twenty-six had Crohn's disease
      (CD), 6 had ulcerative colitis (UC), and 1 had indeterminate colitis (IC). Twenty
      one received rofecoxib, 10 celecoxib, and 2 received both medications at
      different time points. Overall, 13 (39%) patients experienced disease
      exacerbation, 7 of which had received celecoxib and six rofecoxib. IBD
      exacerbation associated with COX-2 treatment did not correlate with age, disease
      activity, or use of immunosuppressive medications. All patients experienced flare
      up of their underlying IBD within 6 weeks of initiating COX-2 therapy. Five of 13
      (38%) patients had resolution of their symptoms after discontinuing the COX-2
      inhibitor, but the remaining patients required additional medical therapy to
      control their disease. Six other patients (18%) experienced GI side effects not
      associated with their underlying IBD. Five developed abdominal pain, and one
      developed a duodenal ulcer and a circumferential ileo-colonic ulceration with GI
      bleeding. Treatment with COX-2 inhibitors is associated with a high incidence of
      exacerbation of the underlying IBD and GI-related complications.

PMID- 15475743
TI  - Pediatric jejunoileitis: a severe Crohn's disease phenotype that requires
      intensive nutritional management.
AB  - BACKGROUND: Jejunoileitis (JI) is an unusual manifestation of Crohn's disease
      (CD) that has been associated with high morbidity and the frequent need for
      surgical intervention. Although the disease has been well-described in adults,
      the true prevalence and clinical phenotype in children is unknown. AIM: To
      compare the clinical course and nutritional impact of CD in children with and
      without proximal small bowel involvement. METHODS: Patients with either Crohn's
      jejunitis or JI with or without colonic involvement were identified through a
      clinical database (1996--2002). All radiologic studies were reviewed by an
      experienced radiologist blinded to the clinical diagnosis. Thirty-six patients
      with CD without histologic or radiologic signs of proximal small bowel
      involvement were used for comparison. All medical, surgical, and hematologic
      parameters were compared in both disease groups. RESULTS: Among the 134 patients
      with CD, 23 (17%) had radiologic signs of JI, including intestinal fold
      thickening (57%), luminal narrowing (31%), and skip lesions (13%). Enteric
      fistula (6%) and strictures (6%) were less common. Patients with JI were likely
      to be stunted at the time of diagnosis, require surgical intervention (P < 0.03)
      and nutritional therapy in the form of nasogastric tube feeds (P < 0.03).
      Nutritional therapy was also associated with an improvement in height in patients
      with proximal small bowel disease (OR:5.87). DISCUSSION: JI is a relatively
      common disease phenotype in children with CD that requires aggressive nutritional
      and surgical intervention. Future studies are required to determine if the early
      detection and use of immune modulators may lessen the morbidity associated with
      proximal small bowel disease.

PMID- 15475744
TI  - Formation of platelet-leukocyte aggregates in inflammatory bowel disease.
AB  - OBJECTIVES: Formation of platelet-leukocyte aggregates (PLAs) is increased in
      several inflammatory and thrombotic conditions. This may result from and enhance
      platelet and neutrophil activation and could contribute to the inflammatory
      process in inflammatory bowel disease (IBD). We investigated platelet-leukocyte
      aggregation in patients with IBD and its relation to treatment, disease activity
      and platelet and neutrophil activation. METHODS: PLAs, platelet activation (P
      selectin expression) and neutrophil activation (L-selectin expression) were
      assessed 30 and 180 minutes after drawing blood into EDTA/citrate-theophylline
      adenosine and dipyridamole, a novel anticoagulant, using fluorescent antibodies
      to CD45 (for leukocytes), CD42a (for platelets), CD62P (P-selectin) and CD62L (L
      selectin) and flow cytometry. Platelet activation was also measured using the
      ADVIA 120 hematology analyser. RESULTS: Samples from 67 patients with IBD
      measured within 30 minutes had a higher platelet count (P < 0.001), more
      platelets expressing P-selectin (P = 0.01), and more PLAs (P < 0.01) than from 20
      healthy controls and more PLAs (P < 0.05) than from 9 controls with inflammatory
      arthropathies. IBD patients on thiopurines had fewer PLAs than those not taking
      them (P < 0.05); corticosteroids and aminosalicylates had no such effects.
      Incubation for 180 minutes increased the number of platelets expressing P
      selectin (P < 0.0001), and the number of PLAs (P < 0.0001). The PLAs correlated
      with the number of platelets expressing P-selectin before (r=+0.40, P < 0.001)
      and after (r=+0.66, P < 0.0001) incubation. CONCLUSIONS: The number of PLAs is
      higher in patients with IBD than in healthy and inflammatory controls, but their
      numbers are lowered by thiopurines. Increased PLA formation may in part be due to
      increased platelet activation and could be pathogenic in IBD.

PMID- 15475745
TI  - Clinical relevance of transabdominal ultrasonography and magnetic resonance
      imaging in patients with inflammatory bowel disease of the terminal ileum and
      large bowel.
AB  - BACKGROUND: Ileocolonoscopy represents the diagnostic standard in the work-up of
      patients with inflammatory bowel diseases (IBD). Patients are often reluctant to
      be colonoscoped because of the invasiveness and pain sensation during
      colonoscopy. AIMS: To compare the usefulness oftransabdominal ultrasound (US) and
      magnetic resonance imaging (MRI) in assessing disease extension and activity in
      patients with IBD restricted to the terminal ileum and large bowel. PATIENTS AND
      METHODS: 61 patients with IBD [37 Crohn's disease (CD) and 24 ulcerative colitis
      (UC)] were prospectively studied. All patients underwent clinical and laboratory
      assessment, ileocolonoscopy, transabdominal sonography, and MRI within 5 days.
      Involved bowel segments were defined as those with bowel wall thickness >3 mm and
      increased Doppler signal on US or contrast enhancement of the bowel wall on MRI.
      To compare disease activity endoscopic, MRI and US findings were graded with
      newly developed scores. RESULTS: The segment-by-segment analysis revealed an
      overall accuracy of 89% for US and 73% for MRI in identifying active IBD. The
      accuracy was better in patients with UC than in patients with CD for both US and
      MRI. The endoscopic activity index (EAI) correlated stronger with the US activity
      index (r = 0.884) than with the MRI activity index (r = 0.344). The correlation
      of US and MRI activity indices with EAI was better in patients with UC compared
      with patients with CD. All three imaging methods showed a significant correlation
      with clinical disease activity in patients with UC but not in patients with CD.
      CONCLUSION: This study provides strong evidence that US should be considered as a
      first-choice method for follow-up of patients with IBD of the terminal ileum and
      large bowel.

PMID- 15475746
TI  - Shortened questionnaire on quality of life for inflammatory bowel disease.
AB  - Questionnaires for measuring quality of life in patients with inflammatory bowel
      disease usually include a large number of items and are time-consuming for both
      administration and interpretation. Our aim was to elaborate and validate a short
      quality-of-life questionnaire with the most representative items from the Spanish
      version of the 36-item Inflammatory Bowel Disease Questionnaire (IBDQ-36) using
      the Rasch analysis. The responses to 311 IBDQ-36 questionnaires from 167 patients
      with ulcerative colitis (UC) and 144 with Crohn's disease (CD) were analyzed.
      IBDQ-36 was shortened with successive Rasch analyses until all the remaining
      items showed acceptable separation and goodness-of-fit properties. Validation of
      the short questionnaire was studied in a new group of 125 patients by determining
      its validity and reliability. A 9-item short questionnaire was obtained (IBDQ-9).
      Its correlation with IBDQ-36 was excellent (r = 0.91). Correlation between IBDQ-9
      and clinical indices of activity was statistically significant in UC (r = 0.70)
      and CD (r= 0.70). IBDQ-9 score discriminates adequately between patients in
      clinical remission or relapse (P < 0.01). Sensitivity to change was determined in
      14 patients who improved clinically, showing significant IBDQ-9 changes between
      both determinations (P < 0.01), with an effect size of -2.67 in UC and -5.29 in
      CD. IBDQ-9 was also homogeneous, with a Cronbach's alpha of 0.95 in UC and 0.91
      in CD. In 35-clinically stable patients, test-retest reliability was good, with a
      statistically-significant correlation between both questionnaires (r = 0.76 in UC
      and 0.86 in CD, P < 0.01) and an intraclass correlation coefficient of 0.82 in UC
      and 0.84 in CD. In conclusion, a short and valid questionnaire to measure quality
      of life in patients with inflammatory bowel disease was obtained using a new
      measurement model. Its use should facilitate comprehension of the impact of
      inflammatory bowel disease.

PMID- 15475747
TI  - The role of quality of care in health-related quality of life in patients with
      IBD.
AB  - In the literature there are indications of associations between health-related
      quality of life (HRQoL) in inflammatory bowel disease and disease activity,
      psychological status, coping, stressful life events, and social support. The aim
      of this study was to examine whether a relation exists between quality of health
      care and HRQoL, taking possible confounding variables into account. For this
      purpose, one single questionnaire was compiled from existing validated
      questionnaires. A population-based inception cohort of 1056 patients with
      inflammatory bowel disease in eight countries, diagnosed 6 to 8 years prior to
      the study, was approached to participate. In total, 824 patients responded (78%),
      and 517 could be included in statistical analyses. It was shown that in
      inflammatory bowel disease HRQoL was indeed influenced by quality of care
      (particularly with regard to the parameters of "providing information," "costs,"
      and "courtesy"), as well as by disease activity, psychological status, type of
      hospital, social support, stressful life events, and way of administration of the
      questionnaire. Patients with active disease had lower psychological status and
      HRQoL scores at the time of the survey than patients without active disease.
      However, quality of care scores did not differ between these groups. The care
      aspect "costs" was scored worse by CD compared with UC patients, probably caused
      by a potentially more expensive treatment. In conclusion, it is shown in a large
      exploratory study, for the first time, that in inflammatory bowel disease,
      quality of care has a significant role in determining health-related quality of
      life.

PMID- 15475748
TI  - Biopsychosocial determinants of health-related quality of life after ileal pouch
      anal anastomosis for ulcerative colitis.
AB  - BACKGROUND: In patients with ileal pouch anal anastomosis (IPAA) the influences
      of psychosocial variables and of extraintestinal manifestations of ulcerative
      colitis (UC) on health-related quality of life (HRQOL) have not been studied so
      far. METHODS: 61 patients with UC (age 52.7+/-13.9 years; 47% female) completed
      the German version of the Inflammatory Bowel Disease Questionnaire (IBDQ-D), the
      Short Form Health Survey (SF - 36), the German version of the Hospital Anxiety
      and Depression Scale (HADS-D) and the Giessener Symptom List (GBB 24).
      Independent of their current clinical activity 37 patients underwent endoscopies.
      Pouchitis was defined by the Pouch Disease Activity Score (PDAI) > or = 7. Where
      possible, IPAA-patients were compared with the data for the German general
      population and with a clinical sample of patients with UC and no IPAA. RESULTS:
      Patients with IPAA complained more about fatigue and arthralgia and a reduced
      physical and mental health (SF-36) than the German general population (P < 0.01).
      The IBDQ-total score could be predicted (adjusted R2 = 29.1, P < 0.01) by the
      number of operations due to IPAA-related complications (beta = -18.8) and HADS-D
      Anxiety scores > or = 11 (beta = -29.1). The IBDQ-subscale score "Bowel" could be
      predicted (adjusted R2 = 13.7, P = 0.04) by PDAI > or = 7 (beta = -9.2) and the
      subscale score "Systemic" (adjusted R2 = 13.3, P = 0.04) by the number of
      extraintestinal manifestations (beta = -1.9). CONCLUSIONS: HRQOL of patients with
      UC and IPAA is determined not only by IPAA-related factors but also by anxiety
      and extraintestinal manifestations with associated musculoskeletal pain.

PMID- 15475749
TI  - Galanin contributes to the excess colonic fluid secretion observed in dextran
      sulfate sodium murine colitis.
AB  - Galanin is present in enteric nerves lining the gastrointestinal (GI) tract where
      it is normally involved in regulating intestinal motility by binding to the
      galanin-1 receptor (Gal1R) subtype expressed by smooth muscle cells. In contrast,
      although epithelial cells lining the colon do not normally express Gal1R, this
      protein is up-regulated by the inflammation-associated transcription factor NF
      kappaB. We previously showed that the murine colitis induced by dextran sulfate
      sodium (DSS) was associated with increased Gal1R expression as well as by
      increased colonic fluid secretion. Although Gal1R up-regulation by colonic
      epithelial cells results in increased intestinal Cl- secretion, the relative
      contributions of galanin to this excess colonic fluid secretion could not be
      determined. We therefore created a mouse genetically incapable of synthesizing
      Gal1R (GAL1R-/- mice). We herein demonstrate that both wild-type and GAL1R-/-
      mice developed identical histologic lesions in response to DSS. This was
      characterized by a marked inflammatory infiltrate, activation of NF-kappaB in
      both enterocytes and enteric nerves, and a threefold increase in neuronal
      galanin. Colonic fluid secretion, while increased, was approximately half that in
      GAL1R-/- mice as compared with their wild-type littermates. Overall, then, these
      findings strongly suggest that approximately half of the increase in colonic
      fluid secretion in DSS colitis is due to up-regulation of the Gal1R.

PMID- 15475750
TI  - Infliximab therapy in pediatric Crohn's pouchitis.
AB  - OBJECTIVE: We describe the prolonged clinical benefit of murine chimeric
      antitumor necrosis factor (TNF)-alpha monoclonal antibody, infliximab, on
      pediatric patients with Crohn's disease and ileal pouch anal anastomosis (IPAA).
      METHODS: A retrospective review of patients originally diagnosed with ulcerative
      colitis, status post colectomy and IPAA, who developed findings compatible with
      Crohn's disease was undertaken. Refractory pouchitis developed in all patients as
      well as protracted symptoms of diarrhea, abdominal pain, joint pain, and
      incontinence. All patients received infliximab. RESULTS: Four pediatric patients
      (2 males and 2 females) with mean age of 14.5 years (range 11-18 years) were
      studied. The development of perianal fistulas in 2 patients, granuloma on biopsy
      in 1 patient and perianal skin tag in 1 patient, led to a diagnosis change of CD.
      After failure to respond to antibiotics, aminosalicylates and immunomodulators
      such as azathioprine and 6-mercaptopurine (6-MP), all patients were treated with
      infliximab. Patients received infliximab infusions at a dose of 5 mg/kg,
      initially at weeks 0, 2 and 6 and subsequently at 8 weeks intervals in
      combination with an immunomodulator drug. All patients showed marked improvement
      clinically, endoscopically, and histologically. CONCLUSION: Infliximab can be
      used successfully for the treatment of pediatric patients with Crohn's disease
      and IPAA who are refractory to conventional therapies.

PMID- 15475751
TI  - Successful therapy of refractory pyoderma gangrenosum and periorbital phlegmona
      with tacrolimus (FK506) in ulcerative colitis.
AB  - We describe two male patients with ulcerative colitis and refractory pyoderma
      gangrenosum including periorbital phlegmona in one case. Both patients were
      successfully managed with low dose oral tacrolimus (0.1 mg/kg bodyweight per
      day). Serum trough levels were closely monitored and maintained between 4 and 6
      ng/mL. A rapid response was noted in both cases. Complete non-scarring skin
      restitution without side effects was accomplished in both cases. Low dose oral
      tacrolimus provides a valuable alternative treatment option for IBD patients with
      refractory pyoderma gangrenosum.

PMID- 15475752
TI  - Epstein-Barr virus-associated lymphoma in Crohn's disease.
AB  - Although no increased risk of developing lymphoproliferative disorders has been
      observed in population-based studies of patients with Crohn's disease, the
      possibility has been suggested in the subset of patients previously treated with
      thiopurine metabolites and suffering from concomitant Epstein-Barr virus
      infection. A few cases of lymphomas have occurred in patients with Crohn's
      disease treated with infliximab, only one of whom showed the presence of the
      Epstein-Barr virus genome. We here describe the case of a patient with steroid
      dependent ileal Crohn's disease treated with azathioprine and a single infusion
      of infliximab, who developed a diffuse large B cell ileal lymphoma. Epstein-Barr
      virus genome was detected in the neoplastic cells by means of polymerase chain
      reaction. Epstein-Barr virus may be detected in the neoplastic tissues of
      lymphomas of patients with Crohn's disease treated with immunosuppressants and
      infliximab. The identification of such cases may help to define the frequency of
      this association and how to manage the lymphoproliferative disorder.

PMID- 15475753
TI  - Aortic mural thrombi in patients with inflammatory bowel disease: report of two
      cases and review of the literature.
AB  - Thromboembolic events are a known complication in inflammatory bowel disease
      (IBD). We report on 2 young women with IBD and aortic mural thrombi as a source
      of arterioarterial embolization to the lower limbs resulting in significant
      morbidity. The first case was a 36-year-old woman with severe ulcerative colitis
      who presented with signs of microembolism into two toes of her right foot. A
      thrombus in the otherwise normal infrarenal aorta with occlusion of the inferior
      mesenteric artery was revealed by computed tomography (CT) and intrarterial
      angiography. The digital ischemia resolved without sequelae. The second case was
      a 41-year-old woman with Crohn's disease complicated by fistulas. She developed
      acute ischemia of her right leg. Arteriography and CT revealed infrapopliteal
      embolic occlusions and a thrombus in the distal otherwise normal abdominal aorta
      and the left iliac artery. A primarily successful thrombectomy had to be repeated
      5 times because of reocclusion. Eventually the leg was exarticulated at the knee.
      In both patients no further thromboembolic event occurred during follow-up of 4
      1/2 years and 5 1/2 years, respectively, and aortic thrombi had resolved at
      follow-up CT scans. Extensive work up for hypercoagulability was negative in both
      patients. We consider IBD as the most likely trigger for arterioarterial
      embolization in the absence of thrombophilia in both patients. Finally we give an
      overview of the literature of similar cases with aortic mural thrombi in IBD
      patients.

PMID- 15475754
TI  - Pneumocystis jiroveci (carinii) pneumonia following initiation of infliximab and
      azathioprine therapy in a patient with Crohn's disease.
AB  - Anti-TNFalpha therapy is an effective treatment of Crohn's disease. There is an
      increased risk of infection, including atypical infection associated in
      infliximab treated patients. We report a case of a young man who developed
      Pneumocystisjiroveci pneumonia shortly after starting therapy with infliximab.
      Thus, although rare, prophylaxis against Pneumocystis jiroveci pneumonia might be
      considered when starting a treatment with infliximab, especially in patients
      receiving concomitant immunosuppressive agents.

PMID- 15475755
TI  - Colonic sarcoidosis, infliximab, and tuberculosis: a cautionary tale.
AB  - The antitumor necrosis factor, infliximab, has been recently shown to be
      effective in refractory sarcoidosis including the intestinal form of this
      disease. We have tried this therapy in a 55-year-old woman under
      immunosuppressive therapy for longstanding sarcoidosis presenting with abdominal
      pain apparently caused by a colonic localization of the disease. The latter
      diagnosis was based, as recommended, on the presence of nonnecrotizing granulomas
      in mucosal biopsies, the presence of systemic disease, and the careful exclusion
      of other granulomatous diseases, including tuberculosis. After the first IV
      infusion (10 mg/kg BW), she quickly improved, but the wellbeing lasted
      approximately 4 weeks. She then received another dose of infliximab, but she soon
      developed low-grade fever and weakness and shortly succumbed of miliary
      tuberculosis. Likely, infliximab precipitated a pre-existing mycobacterial
      infection of the intestine. Given the likelihood of underdiagnosing intestinal
      tuberculosis--and the risks associated with infliximab treatment--this case
      suggests that this drug should be used with extreme caution, if at all, when a
      diagnosis of colonic sarcoidosis is suspected.

PMID- 15475756
TI  - The myth of gastrointestinal sarcoidosis: a case of guilt by association.

PMID- 15475758
TI  - Editorial Comment on Communicating with Patients with Inflammatory Bowel Disease.

PMID- 15475757
TI  - Communicating with patients with inflammatory bowel disease.
AB  - Ulcerative colitis and Crohn's disease, the two main forms of inflammatory bowel
      disease (IBD), are chronic illnesses that affect hundreds of thousands of
      Americans. Patients with IBD suffer chronically from diarrhea, abdominal pain,
      gastrointestinal bleeding, malabsorption, and weight loss requiring continuous
      medical and surgical attention. Despite recent advances in therapy, IBD follows a
      course of exacerbations and remissions with approximately 25-50% of patients
      relapsing annually. Hence, these diseases are readily encountered in primary care
      and gastroenterology clinics. Though medical and surgical treatment options have
      improved significantly, little has been written about the psychosocial aspects of
      IBD. Currently, there is a paucity of data concerning effective communication
      methods enabling physicians to develop stronger rapport with patients suffering
      from IBD, the care of whom requires a multidisciplinary approach involving
      primary care physicians, gastroenterologists, and colorectal surgeons. Because
      IBD has a high morbidity, it is worthwhile to further investigate those social
      factors that will improve patients' quality of life. In this paper, we summarize
      some of the common problems that emerge when taking care of patients with IBD and
      provide initial guidelines based on the world literature regarding the management
      and education of patients with IBD. Both primary care physicians and specialists
      (gastroenterologists, colorectal surgeons) need to be aware of the questions and
      concerns of IBD patients and to be capable of dispensing the information in a
      clear and concise manner. Using the case scenario format, we review the most
      common aspects of communication for health care professionals taking care of IBD
      patients and suggest ways to establish and maintain long-term doctor-patient
      relationships. The two most significant interventions that dramatically improve
      quality of life and patient-physician relationships are proper patient education
      and appropriate treatment of concurrent depression and anxiety. We hope that our
      review will form a framework by which different members of the medical team learn
      their roles in the complex management decisions affecting IBD patients.

PMID- 15475759
TI  - Modern imaging of Crohn's disease using bowel ultrasound.
AB  - Technological advancement of ultrasound (US) equipments and understanding of
      bowel appearances with high resolution US during the last decade has led to
      consideration of this imaging procedure as an important tool for inflammatory
      bowel diseases assessment. In particular, Crohn's disease (CD) for its pathologic
      characteristics (that is, inflammatory infiltration of the entire bowel wall with
      possible extension to the surrounding mesentery) is the disease entity which has
      mainly taken advantage from this non-invasive, radiation-free technique. Beside
      correctly defining anatomic location and extension of CD lesions within the bowel
      in the majority of cases, US also shows perigut abnormalities and may demonstrate
      complications such as fistulas and abscesses. With the help of Power Doppler
      function, some additional information may be obtained about the local activity of
      the disease which is particularly useful in the presence of strictures. New US
      technologies (such as those using intravenous bolus contrast agents or oral
      nonabsorbable anechoic solutions) may further improve diagnostic capability of US
      in this context, thus probably revolutioning the diagnostic approach to this
      disease in the near future, particularly during follow-up in CD of the small
      bowel.

PMID- 15475760
TI  - Mechanisms of natural tolerance in the intestine: implications for inflammatory
      bowel disease.
AB  - Tolerance, the regulated inability to respond to a specific immunologic
      stimulant, is a physiological event important to normal immune function. Just as
      loss of tolerance to self-proteins results in autoimmune diseases, we assert that
      loss of tolerance to commensal flora in the intestinal lumen leads to
      inflammatory bowel disease (IBD). Mechanisms through which the mucosal immune
      system establishes and remains hyporesponsive toward the presence of food
      proteins and commensal flora, which we define as natural tolerance, are
      discussed. In addition to the contributions by commensal flora, the innate host
      defense and the adaptive immune systems promote natural tolerance to sustain
      normal mucosal homeostasis. Understanding the molecular and cellular events that
      mediate natural tolerance will lead to more advanced insights into IBD
      pathogenesis and improved therapeutic options.

PMID- 15475761
TI  - Mucosal healing in pediatric Crohn's disease: the goal of medical treatment.

PMID- 15475762
TI  - Mucosal healing in children with Crohn's disease: appropriate therapeutic goal or
      medical overkill?

PMID- 15475763
TI  - Mucosal healing in pediatric Crohn's disease: Pro/Con balance.

PMID- 15475764
TI  - Gastrostomy use in attempted suicide.

PMID- 15475765
TI  - Safety of infliximab: primum non nocere. The safety profile of infliximab in
      patients with Crohn's disease: the Mayo Clinic experience in 500 patients.

PMID- 15475766
TI  - Making sense of antisense: ISIS 2302 (alicaforsen) in the treatment of pouchitis.
      An enema formulation of alicaforsen, an antisense inhibitor of intercellular
      adhesion molecule-1, in the treatment of chronic, unremitting pouchits.

PMID- 15475767
TI  - Crohn's disease: blame it on the bugs? Antibiotic use and the development of
      Crohn's disease.

PMID- 15475768
TI  - Long-Term Treatment of Crohn's Disease.

PMID- 15475769
TI  - Maintaining remissions across the lifespan: a roundtable discussion with Crohn's
      disease experts.

PMID- 15475771
TI  - Rabbit ear cartilage regeneration with a small intestinal submucosa graft.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to demonstrate that interpositional
      grafting with porcine small intestinal submucosa promotes cartilage regeneration
      following excision of rabbit auricular cartilage. STUDY DESIGN: Blinded,
      controlled study. METHODS: Eight New Zealand white rabbits underwent excision of
      auricular cartilage on two sites with and two sites without preservation of
      perichondrium. Porcine small intestinal submucosa was implanted into one site
      with and one site without intact perichondrium. Remaining sites served as control
      sites. Histological assessment was performed at 3 (n = 4) and 6 (n = 3) months
      and at 1 year (n = 1) after grafting. RESULTS: Histological evaluation showed
      cartilage regeneration accompanied by chronic inflammation in areas in which
      porcine small intestinal submucosa was implanted between layers of intact
      perichondrium. Other sites failed to show significant cartilage regeneration.
      CONCLUSION: The results of the study using porcine small intestinal submucosa as
      a bioscaffold for cartilage regeneration are promising and justify further animal
      and human studies.

PMID- 15475770
TI  - Crohn's is not a 6-week disease: lifelong management of mild to moderate Crohn's
      disease.
AB  - Crohn's disease is an idiopathic, chronic inflammatory disorder of the digestive
      tract with heterogeneous clinical presentations. Crohn's is currently not a
      curable disease, and patients are faced with a lifetime of recurrent disease
      flare-ups and remissions. Management strategies for Crohn's must therefore be
      targeted toward lifelong management, taking into consideration not only the short
      term but also the long-term aspects of the disease. With this in mind, here we
      review the classifications and natural history of Crohn's disease and discuss
      possible predictive factors for the disease evolution in a patient. Here we also
      evaluate the current preferable treatment practices, based on scientifically
      valid research and collective clinical experience, for the management of mild to
      moderate Crohn's disease.

PMID- 15475772
TI  - Percutaneous tracheostomy: don't beat them, join them.
AB  - OBJECTIVES: The introduction of percutaneous tracheostomy (PercTrach) has
      resulted in tension over the scope of practice between otolaryngologists and
      pulmonary/critical care (PCC) specialists. We sought to determine the value of a
      collaborative approach to the performance of PercTrach at the bedside in the
      intensive care unit setting. STUDY DESIGN AND METHODS: A retrospective study of
      consecutive patients who underwent bedside PercTrach at the Medical College of
      Georgia between May of 2003 and November of 2003. All cases were performed in
      conjunction with the PCC team, which typically provided bronchoscopic guidance
      during the performance of the procedure, whereas the PercTrach was performed by
      the otolaryngology team, although these roles were occasionally reversed. In all
      cases, the PercTrach was performed using the Ciaglia Blue Rhino introducer set.
      RESULTS: Twenty-three patients (12 males, 11 females) with a mean age of 47.6 +/-
      14.3 (range 23-65) years underwent PercTrach. The procedural times ranged from 7
      to 21 minutes, with a mean of 13.9 +/- 4.4 minutes; this represented 9.6 minutes
      on average to insert the tracheostomy tube and an additional 4.3 minutes to
      completely secure the tracheostomy tube. The time interval from consultation to
      PercTrach was less than 24 hours in 16 of 23 cases (overall mean time to
      PercTrach = 41.7 +/- 37.1 hours), with delays beyond 24 hours related in most
      instances to patient stability. CONCLUSION: A multidisciplinary approach to
      PercTrach results in a number of clinical and educational benefits. Chief among
      these benefits is a rapid, cost-effective response to requests for elective
      tracheostomy. Practicing otolaryngologists with a prior bias against this
      approach (as we had) should reconsider adopting this revised procedure.

PMID- 15475773
TI  - Laryngeal abscess after injection laryngoplasty with micronized AlloDerm.
AB  - OBJECTIVE: Patients with unilateral vocal cord paralysis usually present with
      dysphonia and occasionally with swallowing problems. Operative management
      includes thyroplasty type I, injection laryngoplasty, arytenoid adduction, and
      reinnervation. Recent publications have documented the safety of micronized
      AlloDerm (Cymetra, LifeCell Corporation, Branchburg, NJ) for injection
      laryngoplasty, but we report the first documented case of a laryngeal abscess
      after injection laryngoplasty with Cymetra. STUDY DESIGN: Single case report of a
      laryngeal abscess after injection laryngoplasty with Cymetra. METHODS: The
      patient's clinical course is presented and discussed, and the pertinent
      literature is reviewed. RESULTS: Prompt hospital admission with intravenous
      antibiotics and steroids resolved this airway emergency. Follow-up visits showed
      a significantly improved postoperative voice with an intact airway. CONCLUSION: A
      review of the literature reveals that this case of a laryngeal abscess after
      injection laryngoplasty with Cymetra is the first of its kind. Studies have shown
      that the use of AlloDerm in the head and neck region is safe, but
      otolaryngologists need to be cognizant of potential complications when working
      with this material.

PMID- 15475774
TI  - Pantoprazole for sleepiness associated with acid reflux and obstructive sleep
      disordered breathing.
AB  - OBJECTIVE: To determine the effectiveness of Pantoprazole (Wyeth Pharmaceuticals
      Inc., Philadelphia, PA) therapy for daytime sleepiness in patients with symptoms
      of acid reflux and obstructive sleep-disordered breathing (OSDB). STUDY DESIGN:
      Prospective interventional cohort study. METHODS: Twenty-seven adult subjects
      (67% men) with symptoms of acid reflux disease and mild to moderate OSDB were
      included in a 3-month study of proton pump inhibitor therapy (Pantoprazole 40 mg
      once daily). Primary outcomes included changes in daytime sleepiness, reflux
      symptoms, and bed partner assessment of snoring. Secondary outcomes included
      changes in snoring quantification, apnea, and apnea-hypopnea indices (AHI) with
      SNAP Laboratories (Glenview, IL) home sleep study and self-reported global
      symptom improvement. RESULTS: At baseline, patients were typically middle-aged,
      obese men with mild to moderate sleep apnea (mean AHI = 15) with excessive
      daytime somnolence (mean Epworth Sleepiness Score = 13). After 3-month treatment
      with Pantoprazole, a statistically significant improvement was noted for daytime
      sleepiness (P = .002) and total reflux symptoms (P = .0006). Subjects also
      reported a significant reduction in reflux awakening them from sleep (P < .0001).
      Bed-partner assessment of snoring significantly improved (P = .03); however, no
      significant improvements were noted in snoring quantification, apnea, or AHI.
      When compared with a disease-severity matched historic placebo-control group,
      this cohort demonstrated a significantly greater reduction in daytime sleepiness
      (P = .04). CONCLUSIONS: This cohort of subjects had significant improvements in
      daytime sleepiness and reflux symptoms, including reflux awakening from sleep,
      with Pantoprazole therapy. Further controlled studies are indicated to confirm
      these results. Improvement in daytime somnolence likely resulted from a reduction
      in reflux-related arousals because no improvements occurred in OSDB.

PMID- 15475775
TI  - Cricoid chondrosarcoma presenting as arytenoid hypertelorism.
AB  - BACKGROUND: Arytenoid hypertelorism (arytenoid cartilages spaced too widely
      apart) appears to be the most common initial recognizable physical finding of
      cricoid chondrosarcoma. Nine cases from the Center for Voice Disorders are
      presented. With arytenoid hypertelorism caused by cricoid chondrosarcoma, usually
      the posterior larynx is open. In fact, patients with arytenoid hypertelorism
      caused by cricoid chondrosarcoma may be aphonic even though the anterior
      membranous vocal folds make contact during attempted phonation. METHODS: Between
      1991 and 2002, nine patients were diagnosed with cricoid chondrosarcoma.
      Patients' charts and video examinations were retrospectively evaluated for
      symptoms and the presence of arytenoid hypertelorism on endoscopic evaluation.
      Two were women, and seven were men, with a mean age of 70 (range 53-72) years at
      diagnosis. RESULTS: Eight (88%) patients had aphonia or dysphonia caused by
      arytenoid hypertelorism as their presenting symptom. Six were diagnosed after
      failed medialization laryngoplasty or other laryngeal rehabilitation surgery. All
      nine patients had a low-grade tumor. The initial treatment in eight patients was
      hemicricoidectomy, and one patient had a total laryngectomy. In four cases, a
      second procedure was needed 1 to 6 years later because of recurrence. Seven
      patients are alive without clinically significant disease; one is alive with
      moderate disease, and one has died from an unrelated cause. CONCLUSIONS: Severely
      dysphonic, elderly patients presenting with arytenoid hypertelorism of unknown
      cause should be evaluated by fiberoptic laryngoscopy and by computed tomography
      scan to rule out cricoid chondrosarcoma. Because these tumors behave so benignly,
      the authors recommend conservative surgery (unilateral hemicricoidectomy) as the
      diagnostic/treatment modality of choice.

PMID- 15475776
TI  - Chronic rhizopus invasive fungal rhinosinusitis in an immunocompetent host.
AB  - HYPOTHESIS: Rhizopus species may cause chronic invasive fungal rhinosinusitis in
      an immunocompetent host. STUDY DESIGN: Individual case report. METHODS: Review of
      inpatient and outpatient records, radiographic studies, pathologic examination,
      and microbiology of the presented case. Review of the literature. RESULTS:
      Rhizopus species may be the cause of chronic invasive fungal rhinosinusitis in an
      immunocompetent host and result in intracranial extension.

PMID- 15475777
TI  - Cochlear implantation in adults with prelingual deafness. Part I. Clinical
      results.
AB  - OBJECTIVES/HYPOTHESIS: To examine the hypothesis that the newer generations of
      cochlear implants could provide considerable speech understanding to late
      implanted, prelingually deaf adult patients. STUDY DESIGN: Retrospective review.
      METHODS: Speech perception scores of 103 patients with long-term prelingual
      deafness obtained from the recent clinical trials were compared with other
      previously published results. RESULTS: Unlike patients receiving implants in
      early childhood, the audiologic performance of most patients with long-term
      prelingual deafness rapidly approached asymptotic levels within 1 year after
      implantation. Beginning at 3 months postimplantation, statistically significant
      improvement was noted in their speech perception scores compared with their
      preimplant levels. However, the average performance plateau achieved by this
      group of patients was significantly below the levels published for postlingual
      patients. No statistically significant differences were observed between the test
      scores at any testing interval among patients with different devices.
      CONCLUSIONS: Most patients with long-term prelingual deafness achieve their
      performance plateau within 1 year after implantation. The results suggest that
      patient characteristics, rather than device properties, are likely to be the
      major contributing factor responsible for the observed audiologic outcomes.

PMID- 15475778
TI  - Is nasal packing necessary following endoscopic sinus surgery?
AB  - OBJECTIVES/HYPOTHESIS: To determine the necessity of nasal packing or hemostatic
      agents or both following endoscopic sinus surgery. STUDY DESIGN: Retrospective
      review of cases in a tertiary care sinus practice at an academic medical center.
      METHODS: Records of 165 patients undergoing 169 endoscopic sinus surgeries were
      reviewed to determine the presence of adjunctive nasal procedures, the use of
      nasal packing or hemostatic agents or both, blood loss during surgery, and the
      incidence of bleeding complications following surgery. RESULTS: The median
      estimated blood loss during surgery was 50.0 mL (range, 5-1000 mL). In four
      surgeries (2.4%) hemostatic agents were placed in the nose at the conclusion of
      surgery, 19 (11.2%) had packing, and 147 (87.0%) had no material left in the
      nose. No patients had bleeding complications postoperatively. There was a
      significant decrease in the use of packing or hemostatic agents or both over
      time. CONCLUSION: Placement of nasal packing or other hemostatic agents or both
      within the nasal cavity is not necessary in the majority of endoscopic sinus
      surgeries. The risks, costs, and discomforts associated with these interventions
      can often be avoided.

PMID- 15475779
TI  - Pedicled temporoparietal fascial flap reconstruction of select intraoral defects.
AB  - OBJECTIVES/HYPOTHESIS: Multiple modalities exist for reconstruction of oral
      cavity defects following resection. Although microvascular free tissue transfer
      is often the first choice for complex intraoral defect reconstruction, not all
      patients are suitable candidates for "free flaps." The authors present their
      experience with the pedicled temporoparietal fascial flap (TPFF) for
      reconstruction of selected intraoral defects. STUDY DESIGN: Retrospective chart
      review. METHODS: Charts of patients who underwent a TPFF for reconstruction of
      intraoral defects at a tertiary academic institution between 2001 to 2003 were
      reviewed. Information regarding tumor, surgical procedure, complications, and
      results was gathered. The anatomy and surgical technique of using the TPFF for
      intraoral reconstruction were reviewed. RESULTS: Three patients underwent
      reconstruction of an intraoral defect with a TPFF. All defects were on the
      lateral buccal space with significant anterior or posterior extension. All
      patients had specific contraindications for free flaps, including compromised
      donor site or recipient site vascularity and medical comorbidity. The procedures
      were uncomplicated. There was no incidence of flap failure, and all flaps
      accepted a split-thickness skin graft. The average hospital stay was 7 days. An
      oral diet was begun on the fifth postoperative day. The cosmetic result at the
      donor site was excellent. Follow-up has ranged from 7 to 30 months. Mild
      contracture of the flap developed in two patients, limiting mandibular motion.
      CONCLUSION: The TPFF is a thin, vascular, durable flap that is a viable option
      for reconstruction of selected intraoral defects in patients who are not suitable
      candidates for other methods.

PMID- 15475780
TI  - Development and validation of the voice handicap index-10.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to develop an abbreviated voice handicap
      assessment instrument and compare it with the Voice Handicap Index (VHI). STUDY
      DESIGN: Item analysis of the VHI in individuals without voice disorders and
      patients with voice disorders and creation and validation of the abbreviated VHI.
      METHODS: Clinical consensus review of the VHI items was held to prioritize the
      clinical value of each of the VHI items (30 items in all). Item analysis of the
      VHI was performed using the VHI responses of 100 patients with voice problems and
      159 control subjects. The 10 most robust VHI items were selected using the item
      analysis and clinical consensus results to form the Voice Handicap Index-10 (VHI
      10). Statistical analysis comparing the validity of the VHI-10 with the VHI was
      performed with 819 patients representing a wide spectrum of voice disorders.
      RESULTS: Statistical analysis of the VHI and VHI-10 scores from the study group
      showed no statistically significant differences between the VHI and the VHI-10.
      Irrespective of diagnosis, the correlation between the VHI and the VHI-10 was
      greater than .90 (P = .01). The ratios of the VHI-10 to VHI scores for a variety
      of voice disorder categories were analyzed and found to be consistently greater
      than the expected value (33%). This suggests that the VHI-10 may be a more robust
      instrument than the VHI. CONCLUSION: The VHI-10 is a powerful representation of
      the VHI that takes less time for the patient to complete without loss of
      validity. Thus, the VHI-10 can replace the VHI as an instrument to quantify
      patients' perception of their voice handicap.

PMID- 15475781
TI  - Pachydermia is not diagnostic of active laryngopharyngeal reflux disease.
AB  - OBJECTIVE: To determine the change in pachydermia/posterior commissure
      hypertrophy in patients with laryngopharyngeal reflux disease (LPR) on long-term
      acid-suppressive therapy. STUDY DESIGN: Retrospective chart review. METHODS:
      Seventeen patients with LPR who were compliant with long-term acid-suppressive
      treatment and had good control of their symptoms for at least 20 months were
      examined. Pre- and posttreatment still laryngeal images from these patients were
      analyzed by five otolaryngologists blinded to patient information and were scored
      for pachydermia/posterior commissure hypertrophy according to the Reflux Finding
      Score (RFS) subset. Test-retest intraobserver reliability, intergrader
      correlations, as well as a paired t test for means of the data sets were then
      calculated. RESULTS: There was no significant difference in the grading scores
      between the pre- and posttreatment group for degree of pachydermia/posterior
      commissure hypertrophy despite a prolonged treatment interval (mean = 32 months)
      (P = .25). CONCLUSIONS: There is no statistically significant difference in the
      degree of pachydermia/posterior commissure hypertrophy found at diagnosis and
      after long-term acid suppressive therapy in patients with LPR. Therefore, it
      appears that pachydermia, as an isolated finding, is unreliable in determining
      the presence of active LPR.

PMID- 15475782
TI  - Mirror-image reversal of coronal computed tomography scans.
AB  - OBJECTIVES/HYPOTHESIS: Mirror-image reversal of coronal computed tomography (CT)
      scans can be a significant problem in patient care, potentially leading to wrong
      sided surgery and malpractice suits. There is no literature describing the
      problem of mirror-image reversal of coronal CT scans. Generally, medical errors
      are not widely published: however, with the emphasis on reduction of errors in
      medicine, this topic should be openly discussed. STUDY DESIGN: Retrospective
      review of patient care and an assessment of current methods. METHODS: Two cases
      of mirror-image reversal of coronal CT scans were reviewed, and the authors found
      that each case represented a different type of error. In the first case, the
      error was recognized in the operating room. The second case resulted in wrong
      sided surgery, and a lawsuit was filed. These two separate occurrences led to a
      review of the methods for determining right versus left side for orienting and
      labeling of CT scans. Orientation of coronal scans depends on whether the patient
      is prone or supine. Thus, technician input is required. If a labeling mistake is
      made, radiologists may not readily catch the mistake because of the symmetry of
      the head and neck anatomy. RESULTS: A review of the markings on each scan should
      provide the otolaryngologist with enough information to determine whether the
      scan is mislabeled. CONCLUSION: The incidence of mislabeled coronal CT scans is
      unknown. This error can result in inappropriate patient care and lawsuits for
      wrong-sided surgery. Awareness of the potential problem and open discussion of
      interpretation and prevention are necessary.

PMID- 15475783
TI  - Laryngeal findings in users of combination corticosteroid and bronchodilator
      therapy.
AB  - EDUCATIONAL OBJECTIVE: At the conclusion of this article, the readers should be
      able to 1) describe the laryngeal findings in patients who use combination
      therapy for asthma, 2) discuss the mechanism of laryngeal irritation from the use
      of inhalers, and 3) describe possible mechanisms for reducing laryngeal
      irritation and secondary dysphonia from the use of inhalers. OBJECTIVES: To
      describe voice changes and laryngeal findings in patients who are started on
      combination corticosteroid and bronchodilator therapy in the form of a dry powder
      inhaler (DPI). STUDY DESIGN: Retrospective, single-subject design. METHODS:
      Retrospective review of 10 consecutive patients meeting inclusion criteria, who
      presented at the voice center with more than 4 weeks of dysphonia after being
      started on a combination form of asthma medication for control and maintenance
      therapy. All patients were nonsmokers and without history of previous
      identification or excision of vocal pathology. All patients were treated
      previously with a proton pump inhibitor for gastroesophageal reflux. Laryngeal
      videostroboscopic evaluations were performed on all patients. Patients were asked
      to complete a questionnaire regarding their perceived voice change and history of
      medical maintenance therapy for asthma. RESULTS: Dysphonia was present in the
      patients selected for greater than 4 weeks. Patients had been switched to
      combination therapy after previously using traditional two-drug asthma regimens.
      In eight of nine patients, the vocal folds demonstrated areas of hyperemia, with
      plaque-like changes on the surface mucosa. Reduced amplitude of vibration and a
      reduction in mucosal wave propagation were present on videostroboscopy.
      Questionnaires revealed that all patients were initiated on combination DPI
      treatment within the last 6 months. CONCLUSIONS: Dysphonia caused by a change in
      the surface mucosa is a side effect from the use of DPI therapy for asthma. The
      high-impact force during inhalation of the medication and carrier leads to
      deposition of particles in the upper airway. We believe the extent of mucosal
      irritation can be minimized by patient education in the proper delivery of DPI.
      In some cases, however, return of the two medications delivered separately was
      necessary. The irritation of the laryngeal mucosa and return of normal vibratory
      parameters occurred in all patients.

PMID- 15475784
TI  - Retrograde weight implantation for correction of lagophthalmos.
AB  - OBJECTIVES: Gold weight implantation is the most commonly used method for
      surgical correction of paralytic lagophthalmos. Numerous techniques for placement
      of the weight have been described, yet complications with these methods continue
      to occur (implant migration or extrusion, wound infection, failure to correct the
      lagophthalmos, and excessive postoperative ptosis). We developed a retrograde,
      postlevator aponeurosis method for implantation to improve the placement and
      fixation of the weight. This study describes the rationale, technique, and
      surgical outcome of the retrograde approach. STUDY DESIGN: Retrospective
      analysis. METHODS: Data maintained and collected on 25 consecutive cases of
      retrograde upper lid weight implantation for paralytic lagophthalmos. Pre- and
      postoperative photographs were obtained, and patients were followed for at least
      6 months. All procedures were performed by or under the direction of a single
      surgeon at tertiary academic medical centers (University of California, San Diego
      and University of Zurich, Switzerland). RESULTS: Twenty-five consecutive patients
      were evaluated, 16 male and 9 female, ranging in age from 27 to 86 years. There
      were no surgical failures or perioperative complications and no instances of
      implant migration or extrusion. One patient developed a delayed infection
      requiring removal of the implant, and one patient required replacement of the
      gold weight with a platinum chain implant to better fit the contour of her
      eyelid. CONCLUSIONS: Retrograde implantation allows more accurate placement of
      the weight while creating a permanent circumferential seal for fixation. The
      procedure is minimally invasive, less traumatic than previous methods, and
      produces an excellent cosmetic result. The efficacy has been demonstrated in the
      outcome of the 25 cases described in this study.

PMID- 15475785
TI  - Outcomes and achievement of students who grew up with access to cochlear
      implants.
AB  - OBJECTIVES/HYPOTHESIS: To provide long-term speech perception and production,
      educational, vocational, and achievement outcome data for pediatric cochlear
      implant recipients. STUDY DESIGN: This is a retrospective study using consecutive
      referrals of prelingually, profoundly deaf children at the University of Iowa
      Hospitals and Clinics. METHODS: Twenty-seven prelingually deaf young adults who
      received a cochlear implant between the ages of 2 and 12 years participated.
      Outcome measures included device-use information, perceptual information, reading
      results for all participants and educational achievement results for 17 of 27
      participants, educational placement information/vocational information for all
      students, as well as a comparison of the child's educational/vocational outcome
      with that of the parent's educational/vocational outcome. RESULTS: Speech
      perception and production scores were highly correlated. Achievement test results
      indicated that scores were within 1 SD from normative data based on hearing
      individuals. Over 50% of the college-age eligible students enrolled in college.
      This initial group of implant users had a nonuse rate of 11% in the first 3
      years. Eighty-nine percent of the users maintained full-time use for 7 years, and
      71% of this group have maintained full-time use to date. CONCLUSIONS: This cohort
      of cochlear implant users compared favorably with their hearing peers on academic
      achievement measures. Although there was a wide distribution of educational and
      vocational outcomes, the children tended to follow the educational/vocational
      patterns of their parents. As age of implantation decreases, it will be important
      to compare achievement outcomes of this first generation with those of subsequent
      generations of cochlear implant users.

PMID- 15475786
TI  - Nasopharyngeal pH monitoring in chronic sinusitis patients using a novel four
      channel probe.
AB  - OBJECTIVE: To determine the prevalence of acid reflux into the nasopharynx in
      patients with chronic sinusitis. STUDY DESIGN: Prospective study of patients
      presenting to a specialist rhinology practice with chronic sinusitis. METHODS:
      Forty patients with chronic sinusitis underwent ambulatory 24 hour pH testing.
      The mean age of the patients was 56.3 years (25 Female, 15 Male). The studies
      were performed using a specially developed bifurcated 4 channel pH probe,
      incorporating 2 circumferential sensors positioned at the naso- and hypo-pharynx,
      and 2 unidirectional sensors positioned at the proximal and distal esophagus.
      RESULTS: The circumferential band sensors yielded a stable recording largely free
      of artefact allowing meaningful recordings to be obtained from thirty-seven
      patients. Twelve patients (32.4%) were diagnosed with gastroesophageal reflux. A
      total of 809 reflux episodes were recorded. Of these, 596 (73.7%) reached the
      distal esophagus, with 187 (23.1%) and 24 (3.0%) reaching the proximal esophagus
      and hypopharynx respectively. Only 2 episodes (0.2%) were recorded in the
      nasopharynx. This occurred in 2 of 37 patients (5%). CONCLUSIONS: Acid reflux
      into the nasopharynx is a rare event in patients with chronic sinusitis even
      though a significant proportion (32.4%) have abnormal 24 hour pH studies. It is
      likely that alternative mechanisms other than direct acid contact are involved in
      the pathogenesis of chronic sinusitis.

PMID- 15475787
TI  - Voice changes after androgen therapy for hypogonadotrophic hypogonadism.
AB  - OBJECTIVES/HYPOTHESIS: Males with isolated hypogonadotropic hypogonadism (IHH)
      fail to undergo normal sexual development, including the lack of masculinization
      of the larynx. The objective of this study was to measure the mean vocal
      fundamental frequency (MF0) in IHH patients and determine the impact of androgen
      treatment. An additional aim was to compare the MF0 between IHH patients and
      controls. STUDY DESIGN: Prospective observational study. METHODS: Twenty-four
      patients with IHH were identified along with 30 normal males and females. Voice
      recordings were obtained on all subjects. Androgen therapy was administered to
      the IHH patients. The MF0 and serum sex hormone levels were measured before
      treatment and at intervals during therapy. These results were compared with the
      pretreatment data within the IHH group. Voice parameters were also compared
      between the pre- and posttreatment IHH patients and the normal males and females.
      RESULTS: The MF0 in untreated IHH patients was 229 +/- 41 Hz. This was
      intermediate between the normal male (150 +/- 22 Hz, P < .001) and normal female
      patients (256 +/- 29 Hz, P < .01). After treatment, the MF0 in the IHH group
      decreased to 173 +/- 30 Hz (P < .0001); indeed, their posttreatment MF0
      approached that of normal males (P < .08). Serum hormone levels responded to the
      injected testosterone, but these levels did not directly correlate with MF0.
      CONCLUSIONS: MF0 in IHH patients is intermediate between normal male and female
      levels. After treatment with testosterone, these values approach the range of
      normal males. This prospective study details the impact of androgens on the
      larynx and vocal function in patients with IHH.

PMID- 15475788
TI  - Microaspiration in infants with laryngomalacia.
AB  - OBJECTIVES/HYPOTHESIS: Laryngomalacia is the most common congenital laryngeal
      anomaly and the most frequent cause of stridor in infants. Infants with
      laryngomalacia may have associated respiratory symptoms other than stridor. In
      this study, we evaluated whether infants with laryngomalacia have episodes of
      microaspiration by calculating the amount of lipids present in the alveolar
      macrophages. STUDY DESIGN: We reviewed bronchoalveolar lavage (BAL) findings
      obtained in 14 infants with laryngomalacia and in 11 control children. METHODS:
      BAL was performed during flexible fiberoptic bronchoscopy (FFB) to diagnose
      persistent stridor. The presence of microaspiration was determined by evaluating
      the amount of lipid per single macrophage, assigning each cell a score from 0 to
      4 according to the amount of lipid in the cytoplasm. RESULTS: The lipid-laden
      macrophage index was similar in patients and controls (31.5, range 12-177 vs. 45,
      range 35-106). In 5 of the 14 (36%) patients the index exceeded 100, and more
      than 25% of the cells were graded 3 and 4, indicating the presence of
      microaspiration. The lipid-laden macrophage index correlated significantly with
      the number and percentage of BAL neutrophils (Pearson correlation test, r = 0.83,
      P < .001 and r = 0.925, P < .001) as a marker of lung inflammation. CONCLUSIONS:
      Infants with laryngomalacia may have episodes of microaspiration. BAL performed
      during FFB to evaluate stridor may add helpful therapeutic information without
      increasing the risks of the procedure.

PMID- 15475789
TI  - Viscoelastic properties of three vocal-fold injectable biomaterials at low audio
      frequencies.
AB  - OBJECTIVES: Previous measurements of viscoelastic properties of Zyderm were to be
      extended to low audio frequencies, and properties of two other biomaterials not
      previously measured, thiolated hyaluronic acid (HA-DTPH) and Cymetra, were
      obtained. STUDY DESIGN: Rheologic investigation. METHODS: Oscillatory shear
      stress was applied to each sample using a controlled stress rheometer at
      frequencies between 0.01 and 100 Hz with a parallel plate apparatus.
      Versuscoelastic moduli were recorded at each frequency. The calculated resonance
      frequency of the machine and sample were then used to determine the maximum
      frequency at which reliable data existed. Extrapolation functions were fit to
      viscoelastic parameters, which predicted the properties up to 1,000 Hz. RESULTS:
      Frequency trends of Zyderm were similar to those previously reported, whereas
      magnitudes were different. The elastic moduli logarithmically increased with
      frequency, whereas dynamic viscosity demonstrated shear thinning, a condition of
      primary importance for humans to vocalize over a broad frequency range. Previous
      measurements were extended from 15 Hz up to 74 Hz. Differences in magnitude
      between a previous study and the present study were attributed to particulate
      orientation during testing. Cymetra was found to have nearly identical
      viscoelastic properties to those of bovine collagen, both in magnitude and
      frequency trend, with reliable measures extending up to 81 Hz. Rheologic
      properties of the hyaluronic acid gel were the closest match to cadaveric vocal
      fold mucosa in magnitude and frequency trend. CONCLUSIONS: Viscoelastic
      properties of Cymetra and Zyderm are nearly the same and are significantly
      greater than those of vocal fold mucosa. HA-DTPH possesses a good viscoelastic
      match to vocal fold mucosa and may be useful in future lamina propria repair.

PMID- 15475790
TI  - Long-term results of type II thyroplasty for adductor spasmodic dysphonia.
AB  - OBJECTIVES: To assess the outcome of type II thyroplasty in the treatment of
      adductor spasmodic dysphonia (ASD). STUDY DESIGN: Prospective case series.
      METHODS: Thirteen patients with the diagnosis of ASD who were previously treated
      successfully with botulinum toxin therapy were recruited. Type II thyroplasty as
      described by Nobuhiko Isshiki was performed on all the patients. A self-rating
      assessment of the degree of severity and vocal effort were recorded and compared
      preoperatively and during postoperative follow-up. RESULTS: There were four early
      failures in our series, with two caused by friable thyroid cartilage. In the
      early postoperative period, after excluding the early failures, six (66.7%) and
      seven (77.8%) patients had moderate-good improvement in symptom severity and
      vocal effort, respectively. During the follow-up period, a further five patients
      had deterioration of voice quality and were classified as failures. Of these five
      patients, two patients had reversal of their procedure. At the end of the follow
      up period (mean follow-up period of 12 months), six (66.7%) and five (55.5%)
      patients sustained improvement in symptom severity and vocal effort,
      respectively. However, only two (22.2%) and three (33.3%) patients had moderate
      good improvements in symptom severity and vocal effort, respectively, after 12
      months. CONCLUSIONS: Botulinum toxin injection remains the gold-standard
      treatment for ASD in our center. Potential patients for type II thyroplasty need
      to be carefully selected and counseled by a multidisciplinary team of
      otolaryngologists, neurologists, and speech pathologists.

PMID- 15475791
TI  - Temporal bone histopathology in alport syndrome.
AB  - OBJECTIVE: To determine the histopathologic abnormalities within the cochlea in
      Alport syndrome. BACKGROUND: Alport syndrome, which manifests as hereditary
      nephritis and sensorineural hearing loss (SNHL), is caused by mutations in genes
      that code for the proportional, variant3, proportional, variant4, and
      proportional, variant5 chains of type IV collagen. The proportional, variant3,
      proportional, variant4, and proportional, variant5 chains of type IV collagen are
      present in the basement membrane of the organ of Corti. Previous temporal bone
      studies have failed to identify histopathologic correlates for the SNHL. METHODS:
      We examined temporal bones from nine individuals with a clinical diagnosis of
      Alport syndrome. One of our cases also had genetic testing that showed a mutation
      in the type IV collagen proportional, variant5 chain gene. RESULTS: By light
      microscopy, eight of nine cases demonstrated two unique pathologic changes: 1) a
      "zone of separation" between the basilar membrane and overlying cells of the
      organ of Corti and 2) presence of cells filling the tunnel of Corti and
      extracellular spaces of Nuel. The cytologic losses of hair cells, stria
      vascularis, and cochlear neuronal cells were insufficient to account for the
      observed SNHL in our cases. Electron microscopy was performed in four cases; all
      four demonstrated the following: 1) the zone of separation that was observed at
      light microscopy occurred between the basement membrane and the basilar membrane,
      2) the cells within the tunnel of Corti and spaces of Nuel were morphologically
      similar to supporting cells, and 3) the basement membrane of strial capillaries
      and the spiral vessel (under the basilar membrane) were normal. CONCLUSIONS: The
      histopathologic correlates of cochlear involvement in Alport syndrome are
      abnormalities of the basement membrane of cells of the organ of Corti and
      dysmorphogenesis (cellular infilling of the tunnel and extracellular spaces) of
      the organ of Corti. We hypothesize that these abnormalities result in SNHL by
      altering cochlear micromechanics.

PMID- 15475792
TI  - Microsatellite alterations in african americans with head and neck cancer.
AB  - OBJECTIVE: To determine the genetic differences between African Americans (AA)
      and Non-African Americans (NAA) with head and neck squamous cell carcinoma
      (HNSCC). METHODS: DNA was obtained from tumor tissues and peripheral blood from
      18 AA and 19 NAA patients with HNSCC. Microsatellite analysis using a fluorescent
      technique was performed on chromosomal arms 1p, 3p, 4q, 9p, 13q, and 17p.
      Statistical analyses were performed on the molecular and clinical outcome data.
      RESULTS: Based on the Surveillance, Epidemiologic, and End Result (SEER) data
      from southeast Michigan, the incidence rate of HNSCC in AA has been higher than
      for NAA, and the overall 5-year relative survival rate is lower for AA than NAA
      (36.2% vs. 47.6%). In this study, we found that the rate of loss of
      heterozygosity of chromosomal arms 1p, 3p, 4q, 9p, 13q, and 17p ranged from 68.8%
      to 83.3% for HNSCC in AA and from 66.7% to 90.0% in NAA. The difference in the
      rates of microsatellite alterations in chromosomal arms 3p, 4q, and 9p between AA
      and NAA were between 12.5% and 20% and were not statistically significant.
      CONCLUSION: The incidence and clinical outcomes for AA with HNSCC are different
      from that of NAA in southeast Michigan. In our group of patients with HNSCC,
      differences in rates of microsatellite alterations and survival were found
      between AA and NAA; however, these differences were not statistically
      significant. We conclude that genetic difference, as determined by the rates of
      microsatellite alterations, is not predictive of outcome difference between AA
      and NAA HNSCC patients.

PMID- 15475793
TI  - Medicinal use of cocaine: a shifting paradigm over 25 years.
AB  - OBJECTIVES/HYPOTHESIS: Human cocaine research is predicated on data from the
      clinical practice of otolaryngology that are more than 25 years old and predate
      both the cocaine epidemic and the first reported association between cocaine use
      and myocardial infarction. The authors' objective was to reassess the
      epidemiology and toxicity of medicinal cocaine use among otolaryngologists and to
      compare current trends in usage and safety data with previously reported data.
      STUDY DESIGN: An anonymous closed-question survey replicating the methodology of
      a previous study was used. METHODS: The survey was mailed to active members of
      the American Academy of Otolaryngology-Head and Neck Surgery. The survey used a
      closed-question format asking about the use of cocaine, safety measures taken,
      and adverse outcomes and included information about practice type and location.
      Results were compared with previously published data using a chi test with P <
      .05 considered significant. RESULTS: In all, 7815 surveys were mailed. Four
      thousand seventeen otolaryngologists returned the survey, representing a 54%
      response rate. Of the respondents, only 50% had used cocaine in their practice
      during the previous year. Physicians who had been in practice for less than 10
      years were less likely to have used cocaine than those who had been in practice
      for more than 10 years (78% vs. 93% [P < .001]). Compared with the data reported
      in 1977, fewer physicians reported ever using cocaine in their practice (88% vs.
      92% [P < .001]), fewer physicians had used cocaine in their practice at any time
      in the previous 10 years (68% vs. 92% [P < .001]), and a greater number of
      adverse reactions were reported by current respondents (26% vs. 22% [P < .001]).
      Tachycardia and hypertension were the most commonly reported adverse effects.
      Other important adverse events included 14 deaths, survivable cardiac arrest,
      ventricular tachycardia, and seizures. CONCLUSION: The clinical use of cocaine in
      otolaryngology has decreased significantly in the past 25 years as a result of
      discontinuation of use by physicians who had previously used cocaine and an
      increasing number of otolaryngologists who have never used it. This decline may
      reflect a better understanding of its potential toxicities, problems associated
      with storing and dispensing of a tightly controlled substance, increased
      availability of safer alternative medications, or a combination of these.

PMID- 15475794
TI  - Effect of edaravone on streptomycin-induced vestibulotoxicity in the Guinea pig.
AB  - OBJECTIVES/HYPOTHESIS: The effect of topical administration of edaravone to the
      inner ear was investigated in guinea pigs with streptomycin-induced
      vestibulotoxicity. METHODS: Vestibulotoxicity was induced in 20 animals by
      delivery of streptomycin into the inner ear through osmotic pump for 24 hours.
      Edaravone (n = 8, systemic administration group) or saline (n = 6, control group)
      was injected intraperitoneally once a day for 7 days or edaravone-soaked Gelfoam
      was placed on the round window before wound closure (n = 6, topical
      administration group). RESULTS: Yaw head tilt and spontaneous nystagmus were
      observed in all animals after the operation. The number of spontaneous nystagmus
      beats in the topical administration group was statistically less than that in
      other two groups at 12, 18, and 24 hours after the operation. CONCLUSION: The
      study results suggest that topical administration of edaravone better suppresses
      streptomycin-induced vestibulotoxicity than systemic administration.

PMID- 15475795
TI  - Tracheal agenesis in newborns.
AB  - OBJECTIVES/HYPOTHESIS: A series of three newborns with tracheal agenesis is
      described. The preferred methods of diagnosis, description of the clinical
      course, and a review of the pertinent embryology, associated anomalies, and
      clinical management are presented. STUDY DESIGN: A retrospective study of a
      clinical series of referred patients from 2002 to 2003 who were seen at a single
      institution. METHODS: Chart review for clinical course and pathological specimens
      was performed in all cases. Three patients were identified with tracheal
      agenesis. RESULTS: All three newborns died within 48 hours of birth. All of the
      children underwent emergency laryngoscopy and neck exploration. Gross and
      microscopic pathological examination was accomplished on all patients.
      CONCLUSION: Although tracheal agenesis is rare, it may be more common than
      previously thought. The diagnosis is not straightforward, and the prognosis is
      grim. The embryology of the trachea and other foregut derivatives is closely
      related, and associated birth defects are common.

PMID- 15475796
TI  - A prospective trial of sertraline for chronic subjective dizziness.
AB  - OBJECTIVES/HYPOTHESIS: The authors previously reported that selective serotonin
      reuptake inhibitors (SSRIs) reduce chronic subjective dizziness in patients with
      and without psychiatric illnesses. To extend those preliminary findings and test
      the hypothesis that SSRIs may offer a novel treatment for chronic subjective
      dizziness, the authors conducted a prospective study of sertraline in patients
      with dizziness for more than 6 months, in the absence of active physical
      neurotologic illness. STUDY DESIGN: Sixteen-week, prospective, open-label,
      flexible-dose clinical trial. METHODS: Twenty-four patients with subjective
      dizziness for more than 6 months and no active physical neurotologic illness were
      studied. Eighteen patients had major anxiety disorders. Six had minor frustration
      or worry that did not warrant a psychiatric diagnosis. Sertraline was
      administered at a daily dose of 25 mg, which was increased to a maximum daily
      dose of 200 mg. Dizziness, functional impairment, and psychological distress were
      measured using the Dizziness Handicap Inventory (DHI) and Brief Symptom Inventory
      53 (BSI-53). Treatment outcomes were analyzed using repeated-measures
      multivariate analyses of variance, with last observations carried forward.
      RESULTS: Three patients were excluded from data analysis for disqualifying
      medical conditions, one for protocol violations. Fifteen (75%) patients completed
      treatment. Five (25%) withdrew for adverse effects or lack of efficacy. The
      median daily dose of sertraline was 100 mg. Sertraline significantly reduced
      scores on all three DHI subscales and the BSI-53. Eleven of 15 (73%) patients who
      completed treatment had a positive response, including 8 of 11 (73%) with major
      anxiety disorders and 3 of 4 (75%) with no psychopathological conditions. Six
      patients enjoyed a full remission of symptoms. CONCLUSION: Sertraline
      significantly reduced chronic subjective dizziness in patients without active
      physical neurotologic illness, including those with and without psychiatric
      comorbidity.

PMID- 15475797
TI  - The effect of endogenous nitric oxide on cholinergic ciliary stimulation of human
      nasal mucosa.
AB  - OBJECTIVES/HYPOTHESIS: Endogenous nitric oxide (NO) production by inducible
      nitric oxide synthase is enhanced in the nasal ciliated respiratory tract
      epithelium of patients with allergic rhinitis. Recent experimental data have
      suggested endogenous NO to be strongly involved in the complex regulation of
      ciliary activity, the driving force of the mucociliary transport system. The
      authors investigated the effect of endogenous NO on acetylcholine-stimulated
      ciliary activity of human nasal mucosa. STUDY DESIGN: In vitro study. METHODS:
      Cultures of human nasal mucosa explants were incubated with tumor necrosis factor
      alpha and bacterial lipopolysaccharides to enhance endogenous NO production.
      Expression of inducible NO synthase was morphologically demonstrated by
      immunohistochemistry. Ciliary beat frequency was determined by phase-contrast
      microscopy of ciliated epithelium, using a computerized photoelectric technique.
      Stimulation experiments were performed in vitro with acetylcholine and N(G)-nitro
      l-arginine methyl ester (L-NAME), a NO synthase inhibitor. RESULTS: Upregulation
      of inducible NO synthase in the respiratory tract epithelium after stimulation
      with tumor necrosis factor-alpha and lipopolysaccharide was visualized by
      immunohistochemical analysis. Experimental inhibition of enhanced endogenous NO
      production by 10 mol/L L-NAME significantly reduced baseline ciliary beat
      frequency from 8.6 +/- 0.2 to 7.8 +/- 0.2 Hz (P < .05). Cholinergic ciliary
      stimulation above baseline by 10 mol/L acetylcholine was not significantly
      different before (11.5%) or after (10.8%) blocking of endogenous NO production.
      CONCLUSION: Taken together, the study results suggest that baseline ciliary
      activity depends on endogenous NO production but that the extent of cholinergic
      ciliary stimulation is independent of endogenous NO production. The combination
      of the two effects may improve nasal mucociliary clearance of inhaled allergens
      in patients with allergic rhinitis.

PMID- 15475798
TI  - Infratemporal fossa approach to the hypoglossal canal: practical landmarks for
      elusive anatomy.
AB  - OBJECTIVE: At the conclusion of the article the readers should be able to safely
      and reliably find the hypoglossal canal using the infratemporal fossa approach.
      HYPOTHESIS: Very little has been written on the regional anatomy of the
      hypoglossal canal as seen through a transtemporal approach. This project attempts
      to further define the anatomy of the hypoglossal canal and provide the surgeon
      with guidelines for reaching it. Our hypothesis is that the hypoglossal canal can
      be safely and consistently reached by way of the temporal bone with preservation
      of hearing and cranial nerves (CN) IX to XI. STUDY DESIGN: Prospective anatomic
      study. METHODS: The study was performed using cadaver temporal bones.
      Infratemporal fossa Fisch type-A dissections were performed. The hypoglossal
      canal was then completely exposed. The distance from the canal to the jugular
      bulb, carotid artery, round window, lateral canal, and roots of CN IX to XI were
      recorded. RESULTS: Fifteen temporal bones were dissected and measured. The
      position of the hypoglossal canal is consistently located anterior, inferior, and
      medial to the jugular bulb. The distance from midcanal to the jugular bulb and
      the roots of CN IX to XI at the posterior fossa dura was 5.3 mm +/- 0.82 and 7.1
      mm +/- 2.49, respectively. The distance from the carotid artery where it meets
      the jugular vein to the midcanal was 15.3 mm +/- 2.09. The distance from the
      round window to the canal was 21.7 mm +/- 3.17. CONCLUSIONS: The hypoglossal
      canal can be consistently reached using the infratemporal fossa approach. Hearing
      and CN IX to XI can be preserved. The distance from the jugular bulb and roots of
      CN IX to XI can be used as guideposts. If a tumor is involving the bulb, then the
      carotid artery and the round window are the next most reliable indicators of
      position.

PMID- 15475799
TI  - Tumors of the accessory lobe of the parotid gland: a 10-year experience.
AB  - OBJECTIVES/HYPOTHESIS: The differential diagnosis of midcheek masses include
      pathology arising from normal anatomic structures or from variations of normal
      accessory parotid gland tissue. Accessory parotid gland tissue has been described
      as salivary tissue adjacent to Stenson's duct that is separate from the main body
      of the parotid gland. We report our 10-year experience with the diagnosis and
      treatment of eight accessory parotid gland neoplasms that have been followed by
      the senior authors. STUDY DESIGN: This is a retrospective review of our
      experience with eight accessory parotid gland neoplasms. METHODS: A literature
      review and retrospective chart review of our experience with accessory parotid
      gland tumors over the past 10 years. The presentation, evaluation, management,
      treatment, and outcome were recorded. RESULTS: Eight cases of accessory lobe
      parotid tumors were identified, which have been followed since the date of
      initial treatment. All of the patients presented with a slowly growing cheek
      mass. There was one case of carcinoma expleomorphic adenoma, one case of
      undifferentiated carcinoma (small cell carcinoma), one case of basal cell
      adenocarcinoma, one case of benign salivary cyst, two cases of pleomorphic
      adenoma, and two cases of monomorphic adenoma. A standard facelift approach or
      modified Blair incision was used to excise these tumors. CONCLUSIONS: Neoplasms
      of the accessory parotid gland are rare. Management of these tumors include a
      high index of suspicion, good understanding of the anatomy, and meticulous
      surgical approach.

PMID- 15475800
TI  - Serotonin reuptake inhibitors in auditory processing disorders in elderly
      patients: preliminary results.
AB  - OBJECTIVE/HYPOTHESIS: One mechanism associated with degeneration in the elderly
      is the decrease of neurotransmitters. In the central auditory pathway serotonin,
      can be found from cochlear nucleus to the auditory cortex, and it constitutes one
      of the most important neuromodulatory circuits in hearing processing. The present
      study analyzed the action of citalopram, a selective inhibitor of serotonin
      reuptake, in aged patients with normal to moderate sensorineural hearing loss
      (HL) and low performance on auditory processing. STUDY DESIGN/METHOD:
      Prospective, double-blind, randomized, placebo-controlled study. Thirty-eight
      selected patients were randomly divided into two groups. Nineteen patients made
      up group A and received placebo for 60 days. Nineteen patients of Group B
      received 20 mg per day of citalopram for 60 days. Hearing evaluation was
      performed initially and after 60 days and included pure-tone audiometry, speech
      discrimination test (SDT), emittanciometry (acoustic impedance audiometry),
      identification of synthetic sentences with an ipsilateral competitive message
      (SSI/ICM), tests of pitch-pattern sequences (PPS), and the staggered spondaic
      words test (SSW). RESULTS: Comparisons of tests of auditory processing pre- and
      posttreatment in each group showed a statistical improvement in performance on
      all tests in group B after 2 months of therapy. Comparisons pre- and
      posttreatment between groups showed that patients who received citalopram
      presented statistically significantly better results in the SSI/ICM test (P <
      .0001) after treatment. The same comparison in results for the PPS test and the
      SSW test revealed a tendency (P = .09 and 0.058, respectively) toward better
      performance in the group receiving citalopram. CONCLUSION: These preliminary
      results suggest that the use of citalopram can have a positive impact on auditory
      processes in elderly patients with low performance in auditory process.

PMID- 15475801
TI  - High-dose Cisplatin with amifostine: ototoxicity and pharmacokinetics.
AB  - OBJECTIVES/HYPOTHESIS: Ototoxicity is a common side effect of high-dose cisplatin
      treatment. Thiol-containing chemoprotectors ameliorate cisplatin ototoxicity
      under experimental conditions. The trial was initiated to test the efficacy of
      amifostine protection in high-dose cisplatin treatment (125-150 mg/m) for
      metastatic malignant melanoma, to correlate the ototoxic outcome with cisplatin
      pharmacokinetics, and to evaluate the importance of using a selective analytical
      method for the quantification of cisplatin. STUDY DESIGN: Prospective study of 15
      patients with stage IV malignant melanoma. METHODS: Clinical follow-up of
      therapeutic response, pure-tone audiometry, and analysis of cisplatin and its
      monohydrated complex in blood ultrafiltrate by liquid chromatography with
      postcolumn derivatization were performed. Ultrafiltered blood platinum was
      analyzed by inductively coupled plasma mass spectrometry. RESULTS: Ototoxicity
      and gastrointestinal toxicity were the most prominent side effects. Three
      patients ultimately required hearing aids. All patients had audiometric changes
      at one or more frequencies after the second treatment course, and all but one
      patient reported auditory symptoms. No correlation was found between hearing loss
      and blood cisplatin pharmacokinetics. Platinum levels determined by inductively
      coupled plasma mass spectrometry were higher than total platinum levels
      calculated from cisplatin and monohydrated complex concentrations obtained by
      liquid chromatography analysis. CONCLUSION: Ototoxicity was unacceptable despite
      amifostine treatment. Cisplatin pharmacokinetics during the first treatment
      course were not predictive of hearing loss. Amifostine caused a lowering of dose
      normalized area under the concentration-time curve for cisplatin and monohydrated
      complex. Use of the unselective inductively coupled plasma mass spectrometry
      analysis leads to an overestimation of active drug. Selective analysis of
      cisplatin is especially important when evaluating cisplatin pharmacokinetics
      during chemoprotector treatment.

PMID- 15475802
TI  - Efficacy of anti-adhesive barriers in secondary thyroidectomy: an experimental
      study.
AB  - HYPOTHESIS: This study was conducted to compare the effectiveness of two anti
      adhesive barriers (Seprafilm and Interceed) for reducing adhesions after
      thyroidectomy in a rat model. The anti-adhesive barriers are suggested for use in
      repeated surgeries in general and the gynecologic fields in particular. STUDY
      DESIGN: Controlled, randomized study. METHODS: Twenty-eight male Wistar Albino
      rats that underwent right subtotal thyroidectomy were randomly assigned to three
      groups. One group received Seprafilm (n = 10), and the other received Interceed
      (n = 10) as anti-adhesive barriers. The third group was the control group (n =
      8). At postoperative day 14, the rats were killed under general anesthesia, and
      the surgical fields were evaluated for the adhesion formation. The extent of the
      adhesion formation is scored from 0 (no adhesions) to 2 (fibrous adhesions that
      required sharp dissection). Histopathologically, chronic inflammation,
      histiocyte, fibroblast, fibrosis, collagen, vascularization, granuloma, giant
      cell, and fat necrosis were examined. RESULTS: All the subjects in the control
      group, 7 of 10 in the Interceed group, and 4 of 10 in the Seprafilm group needed
      to be dissected bluntly or sharply. There was significant difference between the
      Seprafilm and the control group (P < .05) whereas there was no significant
      difference between the Interceed group and the control group (P > .05). When
      examined histopathologically, the criteria showing adhesion, such as fibrosis,
      fibroblast, and collagen were higher in the control group compared with the
      Seprafilm and Interceed groups. There was no significant difference between the
      Seprafilm and Interceed groups, whereas a significant difference was found
      between these two groups and the control group. CONCLUSION: This study suggests
      that both Seprafilm and Interceed decrease the incidence of posthyroidectomy
      adhesions in a rat model. Both agents showed no foreign body reaction.

PMID- 15475803
TI  - Endonasal dacryocystorhinostomy location of lacrimal sac with forceps.

PMID- 15475804
TI  - The hyoid suspension.

PMID- 15475805
TI  - Using Modified Evan's Blue Dye Test to predict aspiration.

PMID- 15475808
TI  - Temporary pacemakers in critically ill patients: assessment and management
      strategies.
AB  - Temporary cardiac pacing provides electrical stimulation to a heart compromised
      by disturbances in the conduction system causing hemodynamic instability. The use
      of a temporary pacemaker to treat a bradydysrhythmia or in some cases, a
      tachydysryhthmia, is undertaken when the condition is temporary and a permanent
      pacemaker is not necessary or available in a timely fashion. Temporary cardiac
      pacing is utilized in acute situations and for critically ill patient populations
      requiring immediate therapy. This article discusses the various indications and
      contraindications to temporary cardiac pacing therapy, reviews the different
      modalities of temporary pacemakers, and outlines critical considerations in the
      management of patients being treated with a temporary pacemaker.

PMID- 15475809
TI  - Cardiac resynchronization therapy for heart failure management.
AB  - Heart failure (HF) is responsible for an immense burden on our healthcare system.
      The prevalence of this disease continues to increase as a result of an aging
      population, successful treatment of acute coronary syndrome, and the use of new
      pharmacotherapies. Although pharmacotherapy with angiotensin converting enzyme
      inhibitors and beta-blockers shows improvement in morbidity and mortality, the
      overall prognosis of these patients remains poor. Cardiac transplant has limited
      applicability. Conduction disturbances are frequent in patients with advanced
      heart failure and may cause worsening systolic function and ventricular
      dyssynchrony. Biventricular pacing to achieve cardiac resynchronization is a
      recent and promising therapy for HF patients with an intraventricular conduction
      defect. Randomized clinical trials have substantiated that cardiac
      resynchronization therapy (CRT) through biventricular pacing offers significant
      benefit in morbidity and mortality in a select group of HF patients. Because of
      the high incidence of sudden cardiac death in patients with severe HF, the
      combination biventricular pacing with implantable cardioverter defibrillator
      therapy will provide additional benefit. This article provides an overview of CRT
      with the intent of describing ventricular dyssynchrony, the benefits of CRT, and
      the implications for advanced practice nurses.

PMID- 15475810
TI  - Cardiac defibrillation and resynchronization therapies: principles, therapies,
      and management implications.
AB  - Patients with heart failure remain at high risk for sudden cardiac death (SCD)
      and death due to heart failure progression, despite the incorporation of
      pharmacologic agents into clinical practice that have been shown to decrease
      mortality in clinical trials. Most patients experience SCD as their first
      dysrrhythmic event. The implantable cardioverter defibrillator (ICD) effectively
      terminates ventricular tachycardia/fibrillation (VT/VF) aborting SCD. Cardiac
      resynchronization therapy (CRT) complements pharmacologic therapy improving
      cardiac performance, quality of life, functional status, and exercise capacity in
      patients with systolic dysfunction despite optimal medical therapy who have a
      prolonged QRS duration; furthermore, it decreases mortality when compared with
      optimal medical therapy alone. Implantation of a combination CRT and ICD device,
      a CRT-D, reduces mortality by aborting SCD and providing the functional benefits
      of CRT. This article discusses the evolution of CRT-D therapy, the mechanism of
      operation of a CRT-D device, and nursing implications.

PMID- 15475811
TI  - Atrial fibrillation: treatment options and caveats.
AB  - Atrial fibrillation is the most common clinically significant dysrhythmia. It has
      great impact on quality of life especially related to complications such as
      stroke and heart failure as well as functional status and the cost of chronic
      treatment. Pharmacologic treatment strategies are now better defined and more
      efficacious. Side effects of drugs are better understood. Recent clinical studies
      have contributed recommended treatment guidelines. The identification of atrial
      ectopic foci in cardiac venous sites has defined targets for isolation ablations.
      Novel catheter ablation techniques are offering improved prognosis for patients
      with atrial fibrillation.

PMID- 15475812
TI  - Cardiac pacing device therapy for atrial dysrhythmias: how does it work?
AB  - Atrial fibrillation (AF) is the most common dysrhythmia in North America.
      Paroxysmal or persistent AF affects an estimated 2.8 million individuals, causes
      significant morbidity, and is associated with 1 billion dollars in healthcare
      costs each year in the United States. An aging population, the prevalence of
      hypertension, and the emergence of heart failure as the final common pathway of
      heart disease finds us in an age where the incidence of AF is ever increasing and
      the management challenges are indeed an expanding clinical problem. Although
      guidelines for selection of the appropriate pacing mode have been published,
      device therapy for the control of AF and paroxysmal AF is an emerging clinical
      management strategy. In 2001 The American College of Cardiology (ACC)/American
      Heart Association (AHA) published a document to revise the 1998 guidelines for
      device therapy, and even now these guidelines require elucidation and inclusion
      for the use of cardiac pacing device therapy for the control of atrial
      dysrhythmia. Choosing a complex system, in particular for the patient with
      persistent and symptomatic atrial dysrhythmia, is a most intricate challenge for
      the healthcare professional and the healthcare system. Rate dependent effects on
      refractoriness, reduction of ectopy, remodeling of the substrate, and prevention
      of pauses have been described as the potential mechanisms responsible for the
      rhythmic control effect attributed to atrial pacing. However, while permanent
      cardiac pacing is required for patients with symptomatic bradycardia with
      atrioventricular block and AF, the concept of pacing for the primary prevention
      of AF is novel. Pacing algorithms, single site, biatrial, and dual-site atrial
      pacing and site-specific pacing have all been studied as substrate modulators to
      prevent recurrent atrial dysrhythmia.A dilemma exists surrounding the primary
      approach for the control of symptomatic AF with rapid ventricular response. The
      question remains: should it be to maintain the sinus rhythm or to control the
      ventricular response rate to the AF and anticoagulate? Variations in the
      population studied, differences in the pacing algorithms and protocols, and a
      lack of definitive end points account for the variable results of the studies
      completed thus far. With the current data available, it appears that for
      individuals with sinus node dysfunction and paroxysmal AF in combination with a
      bradyarrhythmia indication for pacing, suppression algorithms may play an
      additive role with full atrial pacing in the management and reduction of episodes
      and burden of paroxysmal AF. The goal of these therapies is to reduce the
      symptoms and hopefully decrease the healthcare costs associated with paroxysmal
      and persistent AF with uncontrolled ventricular response.

PMID- 15475813
TI  - Electromagnetic interference in cardiac rhythm management devices.
AB  - Clinicians caring for cardiac device patients with implanted pacemakers or
      cardioverter defibrillators (ICDs) are frequently asked questions by their
      patients concerning electromagnetic interference (EMI) sources and the devices.
      EMI may be radiated or conducted and may be present in many different forms
      including (but not limited to) radiofrequency waves, microwaves, ionizing
      radiation, acoustic radiation, static and pulsed magnetic fields, and electric
      currents. Manufacturers have done an exemplary job of interference protection
      with device features such as titanium casing, signal filtering, interference
      rejection circuits, feedthrough capacitors, noise reversion function, and
      programmable parameters. Nevertheless, EMI remains a real concern and a potential
      danger. Many factors influence EMI including those which the patient can regulate
      (eg, distance from and duration of exposure) and some the patient cannot control
      (eg, intensity of the EMI field, signal frequency). Potential device responses
      are many and range from simple temporary oversensing to permanent device damage
      Several of the more common EMI-generating devices and their likely effects on
      cardiac devices are considered in the medical, home, and daily living and work
      environments.

PMID- 15475814
TI  - Risk stratification and primary prevention of sudden cardiac death: sudden death
      prevention.
AB  - The initial challenge in primary prevention of sudden cardiac death (SCD) lies in
      identifying those at greatest risk, before the index event. Ventricular
      fibrillation is the leading cause of SCD; however, many clinical conditions
      predispose fatal ventricular dysrhythmias. In patients with structural heart
      disease, left ventricular dysfunction is the strongest predictor of SCD.
      Noninvasive markers such as nonsustained ventricular tachycardia, delayed
      potentials, decreased heart rate variability and baroreflex sensitivity, and
      repolarization alternans are further observed to assess risk in ischemic
      cardiomyopathy; however, most of these markers have poor positive predictive
      value and lack specificity. The electrophysiologic study has strong positive
      predictive value, but remains a costly and invasive method for risk
      stratification. In patients with normal hearts, genetic predisposition may
      identify patients at risk but clinical markers are not readily recognized. The
      implantable loop recorder is a useful tool in detecting dysrhythmic causes of
      syncope and identifying patients at risk for SCD.

PMID- 15475815
TI  - Long QT syndrome and other repolarization-related dysrhythmias.
AB  - Until recently, sudden cardiac death in a young person often remained an
      unexplained tragedy. However, in the last decade there have been dramatic
      advances in medical knowledge regarding inheritable dysrhythmias that increase
      the risk of SCD in otherwise healthy young individuals. The primary mechanism in
      this group of dysrhythmias appears to be an alteration of cardiac repolarization.
      In some diseases, the specific genes affected and even precise cellular
      mechanisms have been identified. The information about these diseases is often
      complex and rapidly evolving, challenging both healthcare providers and the
      families who must make important decisions based on emerging and incomplete
      information. The purpose of this article is to describe current understanding of
      the repolarization-related dysrhythmias and discuss the clinical implications for
      advanced practice nurses.

PMID- 15475817
TI  - Diagnosis and treatment of idiopathic ventricular tachycardia.
AB  - Idiopathic ventricular tachycardia in patients with an anatomically normal heart
      is a distinct entity whose management and prognosis differs from ventricular
      tachycardia associated with structural heart disease. The tachycardia's QRS
      morphology on surface electrocardiogram (ECG) predicts the site of origin and is
      commonly classified as right ventricular tachycardia or left ventricular
      tachycardia. The tachycardia is further characterized by clinical features such
      as repetitive monomorphic ventricular tachycardia (VT), paroxysmal sustained VT,
      or catecholamine dependent VT. The responsiveness of VT to adenosine or verapamil
      is useful in differentiating the mechanism, which may be reentry or triggered
      activity. Patients generally tolerate the tachycardia but may present with
      dizziness, syncope, or palpitations. Sudden cardiac death is rare in this patient
      population. Patient work-up should include 12-lead ECG, signal-averaged ECG,
      ambulatory ECG recording, stress testing, and tests to rule out structural heart
      disease such as echocardiography, cardiac angiography, endomyocardial biopsy, or
      magnetic resonance imaging. Treatment options include pharmacotherapy or catheter
      ablation. Although the prognosis of these patients remains excellent, they should
      continue to have periodic cardiac follow-up to rule out latent progressive heart
      disease such as arrhythmogenic right ventricular dysplasia or cardiomyopathy or
      other forms of cardiomyopathies.

PMID- 15475816
TI  - Dysrhythmias and the athlete.
AB  - Young competitive athletes are perceived by the general population to be the
      healthiest members of society. The possibility that highly trained high school
      and college athletes may have a potentially serious cardiac condition that can
      predispose to life-threatening dysrhythmias or sudden cardiac death (SCD) seems
      paradoxical. The occurrence of SCD in young athletes from dysrhythmias is an
      uncommon but highly visible event. Media reports of sudden death in athletes have
      intensified the public and medical interest in medical, ethical, and legal issues
      related to cardiac disorders in the athlete. Developing screening strategies to
      identify conditions associated with sudden death has been the focus of attention
      of experts in the fields of arrhythmology and sports medicine and has resulted in
      Consensus Statements and Guidelines for evaluation of athletes. These guidelines
      provide information and recommendations for detection, evaluation, and management
      of athletes with cardiovascular disorders and criteria for eligibility and
      disqualification from participation in high-intensity and competitive sports.
      Differentiating normal exercise-induced physiologic changes in the heart from
      pathological conditions associated with sudden death is critical for developing
      screening strategies to identify athletes at high risk. This article discusses a
      case report of sudden cardiac death in an athlete followed by a brief review of
      various causes of cardiac dysrhythmias in young athletes and recommendations for
      screening and management of athletes with cardiovascular diseases.

PMID- 15475818
TI  - Diagnosis and management of vasovagal syncope and dysautonomia.
AB  - Vasovagal syncope is a condition better known as neurocardiogenic or neurally
      mediated syncope. Dysautonomic syncope is the irregular neuroautonomic response
      during the body's attempt to maintain homeostasis. Both types of syncope are
      associated with orthostatic hypotension and are nonlethal. The underlying
      pathophysiology manifests the vast symptoms suffered by the individual. Research
      continues to develop new markers to improve diagnostic testing and therapies for
      treatment. Advanced practice nurses now have a new tool with Head-Up Tilt
      Training Programs to offer the patients who suffer from frequent and refractory
      neurocardiogenic and dysautonomic syncope.

PMID- 15475819
TI  - Quality of life issues in patients with implantable cardioverter defibrillators:
      driving, occupation, and recreation.
AB  - In the United States over 350,000 individuals die annually from sudden cardiac
      arrest due to ventricular tachyarrhythmias. Numerous large-scale clinical trials
      have consistently demonstrated that implantable cardioverter defibrillators
      (ICDs) reduce mortality among appropriately selected patients who have survived
      an episode of potentially life-threatening ventricular arrhythmia (secondary
      prevention) or are at risk for ventricular arrhythmia (primary prevention).
      Despite the demonstrated success of the ICD, many patients often experience
      unique physical, emotional, and psychosocial needs that can directly impact their
      overall quality of life (QOL). The most common psychological disturbances
      following ICD implantation include stress, anxiety, depression, or fear, typical
      of any chronic illness. Additionally, ICDs impose unique emotional pressures
      relating to altered body image, painful shocks, and the possibility of hardware
      failure. The random nature of shocks commonly induces feelings of isolation and
      powerlessness and the experience of shocks is directly linked to poor QOL
      outcomes. Lifestyle changes, such as restrictions on driving, eligibility for
      employment, marital and social relationships, sexual intimacy, or participation
      in recreational activities can significantly affect the ICD patient's
      psychological and emotional well-being. The purpose of this article is to review
      the QOL data from several large-scale clinical trials of ICD patients as well as
      to examine specific QOL issues such as driving restrictions, occupational, and
      recreational concerns.

PMID- 15475822
TI  - Usefulness of fasudil, a Rho-kinase inhibitor, to treat intractable severe
      coronary spasm after coronary artery bypass surgery.
AB  - We have recently demonstrated that fasudil, a Rho-kinase inhibitor, is effective
      in suppressing coronary artery spasm in patients with vasospastic angina. Thus,
      blockade of Rho-kinase may provide a novel therapeutic strategy to treat ischemic
      coronary syndrome caused by the spasm. Severe coronary artery spasm still remains
      a life-threatening serious complication of coronary artery bypass grafting
      (CABG). In this study, we examined the inhibitory effect of fasudil in patients
      with intractable severe coronary spasm after CABG. Three patients who underwent
      CABG showed severe myocardial ischemia resistant to intensive therapy with
      intravenous conventional vasodilators, including isosorbide dinitrate (ISDN),
      diltiazem, and nicorandil. Coronary angiography revealed severe coronary spasm in
      native coronary arteries and/or bypass arterial grafts in all patients. Since
      intracoronary and/or intragraft administration of ISDN was ineffective to resolve
      the spasm, we then administered fasudil (1.5 mg/min for 15 minutes) into the
      spastic arteries. Fasudil successfully resolved the spasm and improved myocardial
      ischemia in all patients without any systemic adverse effects. In conclusion, the
      treatment with fasudil may be useful to treat intractable and otherwise fatal
      coronary spasm resistant to intensive conventional vasodilator therapy after
      CABG.

PMID- 15475823
TI  - Comparison of the in vitro electrophysiologic and proarrhythmic effects of
      amiodarone and sotalol in a rabbit model of acute atrioventricular block.
AB  - The mechanisms for the different proarrhythmic potential of antiarrhythmic drugs
      in the presence of comparable QT prolongation are not completely understood. The
      reasons for the lower proarrhythmic potential of amiodarone as compared with
      other class-III antiarrhythmic drugs such as sotalol, a fact that has been well
      established for years, is insufficiently known. Therefore, the aim of our study
      was to assess the different electrophysiologic effects of amiodarone and sotalol
      in a previously developed experimental model of proarrhythmia. In eight male
      rabbits, amiodarone (280-340 mg/d) was fed over a period of six weeks. Hearts
      were excised and retrogradely perfused. Up to eight simultaneous epi- and
      endocardial monophasic action potentials (MAP) were recorded. Results were
      compared with sotalol-treated (10-50-100 microM) hearts (n = 13). Amiodarone and
      sotalol (50 microM and 100 microM) led to a significant increase in QT interval
      (mean increase: amiodarone: 31 +/- 6 ms; sotalol: 41 +/- 4 ms and 61 +/- 9 ms)
      and MAP-duration (mean increase-MAP90: amiodarone: 20 +/- 5 ms; sotalol: 17 +/- 5
      ms and 25 +/- 8 ms) (P < 0.01). In bradycardic (AV-blocked) hearts, MAP
      recordings demonstrated reverse-use dependence and a significant increase in
      dispersion of repolarization (MAP90) in the presence of sotalol (P < 0.01), but
      not in amiodarone-treated hearts (10%; p = ns). Sotalol led to early
      afterdepolarizations (EAD) and torsade de pointes (TdP) after lowering of
      potassium concentration (6 of 13 hearts). In amiodarone-treated, hypokalemic
      hearts, no EAD or TdP occurred. Sotalol changed the MAP configuration to a
      triangular pattern (ratio-MAP90/50: 1.52 as compared with 1.36 at baseline)
      whereas amiodarone caused a rectangular pattern of MAP prolongation (ratio
      MAP90/50: 1.36). In conclusion, these results show no direct correlation between
      the occurrence of TdP and the degree of QT prolongation. Several factors
      including reverse-use dependence, dispersion of repolarization, and the
      propensity to induce early afterdepolarizations but also differences in the
      action potential configuration may help to understand proarrhythmic side effects
      of drugs.

PMID- 15475824
TI  - Biotinyl endothelin-1 binding to endothelin receptor and its applications.
AB  - The endothelin (ET) system consists of two membrane receptor types A and B and
      three 21-mer isopeptides endothelin-1, endothelin-2, and endothelin-3 as ligands.
      This system is involved in many physiological processes such as vasomodulation,
      neurotransmission, embryonic development, renal function, and regulation of cell
      proliferation. In many pathophysiological conditions involving endothelin system,
      the endothelin antagonism could be a possible clinical treatment. Designing of an
      antagonist involves the characterization of the binding of the test compounds to
      the endothelin receptors. This is being carried out using radioactive ligand. A
      simpler and quicker method will be of great advantage. This study reports a non
      radioactive method for establishing the IC50 concentrations of the ligand. This
      method uses biotinylated-endothelin-1 and streptavidin conjugated with
      horseradish peroxidase. Hydroxyl apatite gel is used for separating the bound and
      unbound biotin-tagged endothelin-1. This method is applicable to detergent
      solubilized receptors and purified recombinant receptors. The endothelin receptor
      type A expressed in Pichia pastoris system has been used in this study. We show
      that this method is applicable in Western blot analysis of endothelin-1 and its
      receptor complex. This can be used to localize the receptor molecules as well.

PMID- 15475825
TI  - Comparison of the effects of propofol and pentobarbital on left ventricular
      adaptation to an increased afterload.
AB  - The purpose of this study was to compare the hemodynamic effects of pentobarbital
      and propofol and their effects on cardiovascular adaptation to an abrupt increase
      in left ventricular afterload. Experiments were performed in 12 open-chest pigs
      instrumented for measurement of aortic pressure and flow, and left ventricular
      pressure and volume. In one group (n = 6), anesthesia was obtained with sodium
      pentobarbital (3 mg x kg(-1) x h(-1)), and, in the second group B (n = 6), with
      propofol (10 mg x kg(-1) x h(-1)). Both groups received sufentanil (0.5 microg x
      kg(-1) x h(-1)) and pancuronium bromide (0.1 mg x kg(-1)). Left ventricular
      function was assessed by the slope of end-systolic pressure-volume relationship
      and stroke work. After baseline recordings, left ventricular afterload was
      increased by aortic banding. The cardiovascular adaptations triggered by the
      aortic banding, such as tachycardia, vasoconstriction, and augmentation of
      myocardial contractility were prevented with propofol, suggesting interference
      with the baroreflex. Increase in left ventricular afterload decreased mechanical
      efficiency, regardless of anesthetic agent. These results showed that
      pentobarbital at 3 mg x kg(-1) x h(-1) has less deleterious hemodynamic effects
      than propofol at 10 mg x kg(-1) x h(-1).

PMID- 15475826
TI  - Mechanism of the endothelium-dependent vasodilation and the antihypertensive
      effect of Brazilian red wine.
AB  - The mechanisms involved in the cardioprotector effect of red wine have not yet
      been completely elucidated but probably an endothelium-dependent vasodilator
      action may play a significant role in this effect. Experiments were undertaken to
      determine whether a Brazilian red wine (BRW) induces vasodilation in the
      mesenteric vascular bed (MVB) and an antihypertensive effect was also assessed in
      rats with NO-deficient hypertension. In MVB precontracted with norepinephrine,
      BRW (alcohol-free lyophilized) induces a long-lasting endothelium-dependent
      vasodilation that is not reduced by indomethacin. Inhibition of NO-synthase by NG
      nitro-L-arginine methyl ester (L-NAME) and guanylyl cyclase by 1H-[1,2,3]
      oxadiazolo [4,4-a]quinoxalin-1-one (ODQ) reduces the vasodilator effect of BRW.
      In vessels precontracted with norepinephrine and depolarized with KCl (25 Mm) or
      treated with Ca-dependent K channel blockers charybdotoxin (ChTx) plus apamin,
      the effect of BRW was significantly reduced. However, this effect is not affected
      by ATP-dependent K (KATP) channel blocker (glibenclamide). The residual
      vasodilator effect of BRW observed in vessels pretreated with ChTx plus apamin is
      completely abolished by ChTx plus apamin plus L-NAME. Concentrations of atropine,
      pyrilamine, yohimbine, and HOE 140 that significantly reduced the vasodilator
      effect of acetylcholine, histamine, clonidine, and bradykinin, respectively did
      not change the vasodilator effect of BRW. Chronic oral administration of BRW
      induced a significant reduction in systolic, mean and diastolic arterial pressure
      in rats with L-NAME hypertension. The present results demonstrated that
      vasodilator effect of BRW is dependent on endothelium-derived hyperpolarizing
      factor (EDHF) in combination with nitric oxide (NO). The antihypertensive effect
      of red wine demonstrated in the present study may play a significant role on the
      cardioprotective action of chronic red wine consumption.

PMID- 15475827
TI  - Negative association between circulating total homocysteine and proinflammatory
      chemokines MCP-1 and RANTES in prepubertal lean, but not in obese, children.
AB  - This study investigated in prepubertal obese children (POC), compared with
      prepubertal lean children (PLC), a possible relation among plasma total
      homocysteine (tHcy)-an independent risk factor for future atherosclerosis-and MCP
      1 and RANTES, two circulating chemokines inducing leukocyte transendothelial
      migration (TEM), implicated in the initial stages of the inflammatory part of the
      atherosclerotic process. Seventy-two POC were evaluated for circulating tHcy, MCP
      1, and RANTES, and compared with 42 healthy PLC. The mean adjusted (for age, sex
      as well as log10total insulin, vitB12, folate, total cholesterol, HDL
      cholesterol, log10triglycerides, and log10glucose levels) differences in tHcy,
      MCP-1, and RANTES levels between PLC and POC were all significant [1.16 nmol/mL
      (P = 0.03), 26.6 pg/mL (P = 0.02), and 52.9 pg/mL (P = 0.03), respectively]. In
      PLC, but not in POC, tHcy levels were negatively associated with both circulating
      MCP-1 (B = -1.68, P = 0.007) and RANTES (B = -1.16, P = 0.01) after adjusting for
      age, sex, BMI, as well as log10total insulin, vitB12, folate, total cholesterol,
      HDL cholesterol, log10triglycerides, and log10glucose levels. In conclusion, in
      POC there is a lack, in contrast to PLC, of a possibly autoregulatory, negative
      association of elevated tHcy levels to increased MCP-1 and RANTES levels. This
      could contribute to future, homocysteine-induced atherosclerosis.

PMID- 15475828
TI  - Effect of levosimendan on balance between ATP production and consumption in
      isolated perfused guinea-pig heart before ischemia or after reperfusion.
AB  - Levosimendan is a novel drug developed for treatment of decompensated heart
      failure. Levosimendan is a calcium sensitizer that increases contractile force of
      the myocardium by enhancing the sensitivity of myofilaments to calcium without
      increasing intracellular calcium concentration. The present study was carried out
      to investigate whether levosimendan induces any changes in the phosphorylation
      potential (ie, the balance between ATP production and consumption) in the normal
      heart and in the post-ischemic heart while exerting its positive inotropic
      effect. We show that 0.1 microM levosimendan increased the left ventricle
      developed pressure in the pre-ischemic and in the post ischemic hearts by 16 and
      18% respectively, and the +dP/dt by 16 and 19%, respectively. At that
      concentration levosimendan did not cause any effect on the phosphorylation
      potential (1 x 10(5) M(-1) and 0.2 x 10(5) M(-1) in the pre-ischemic and post
      ischemic heart, respectively) as assessed by P-NMR, although an increased beating
      rate (13%) and oxygen consumption (10%) was observed when adding the drug post
      ischemically. Our findings are consistent with the results of a recent clinical
      trial (RUSSLAN), which showed that levosimendan does not induce ischemia and
      reduces the risk of worsening heart failure and death, in patients with left
      ventricular failure complicating acute myocardial infarction.

PMID- 15475829
TI  - Chronic nitric oxide synthase inhibition prevents new coronary capillary
      generation.
AB  - L-NAME-induced hypertension has been shown to produce concentric (eutrophic)
      remodeling of the heart despite an enhanced afterload. We postulated that nitric
      oxide synthase inhibition could limit coronary capillary growth to explain the
      nature of remodeling. To test our hypothesis, we aimed at determining the effect
      of endogenous and exogenous nitric oxide on coronary neovascularization. Aortic
      and coronary rings from normotensive animals were incubated in a three
      dimensional type I collagen matrix in the presence of L-NAME or the nitric oxide
      donor SNAP. L-NAME inhibited, while SNAP stimulated, neovascularization from
      aortic and coronary rings after 12 days of in vitro incubation. In arterial rings
      harvested from rats treated with L-NAME for 14 days and in which no further in
      vitro treatment was added, only coronary rings showed a reduction in new
      capillary generation. While confirming that chronic L-NAME-treated rats develop
      concentric remodeling, the evaluation of capillary density did not reveal any
      difference as compared with the controls in 3 areas of the myocardium. In
      conclusion, chronic inhibition of nitric oxide synthesis in vivo produces a long
      lasting reduction in the capacity of coronary arteries to generate new
      capillaries in vitro. Thus, our results lend support to the hypothesis that an
      inhibition of new capillary formation could prevent the development of
      compensatory ventricular hypertrophy, in favor of concentric remodeling.

PMID- 15475830
TI  - betaARK1 inhibition improves survival in a mouse model of heart failure induced
      by myocardial infarction.
AB  - Heart failure (HF) is characterized by abnormalities in beta-adrenergic receptor
      (betaAR) signaling, including an increase in betaAR kinase 1 (betaARK1) levels
      and activity. Gene therapy using a peptide inhibitor of betaARK1 (betaARKct) in
      infarcted rabbit hearts has improved compromised cardiac function. To determine
      whether betaARK1 inhibition improves survival in a mouse model of HF induced by
      myocardial infarction (MI), we studied wild-type (WT) and transgenic (TG) mice
      overexpressing betaARKct following MI. There was no difference in infarct size.
      Survival of WT mice with MI was 25% at 26 weeks. In contrast, 92% of betaARKct TG
      mice with MI survived (P = 0.01). betaARKct TG mice with MI at 8 weeks showed
      significantly higher fractional shortening compared with WT mice with MI (25.1 +/
      2.7% versus 14.2 +/- 1.0%; P < 0.05). Moreover, the biochemical betaAR
      abnormalities in WT mice with MI were prevented in betaARKct TG mice with MI. In
      conclusion, betaARK1 inhibition results in a marked increase in survival and
      improved cardiac function in a mouse model of HF induced by MI.

PMID- 15475831
TI  - Angiotensin receptor blockade decreases markers of vascular inflammation.
AB  - A protective role against atherosclerosis can be attributed to angiotensin
      converting enzyme inhibitors (ACE-I), since they have been shown to reduce
      mortality in patients at cardiovascular risk. Since plasma levels of adhesion
      molecules are considered surrogate markers of endothelial cell activation and
      atherogenesis, we compared the levels of adhesion molecules after treatment with
      the ACE-I enalapril or the direct angiotensin- receptor antagonist losartan or
      placebo. In a randomized, controlled trial, 21 hypercholesterolemic volunteers
      received 50 mg/d losartan or 20 mg/d enalapril or placebo for twelve weeks.
      Plasma levels of circulating intercellular adhesion molecule-1 (cICAM-1),
      vascular adhesion molecule-1 (cVCAM-1), and E-selectin (cE-SEL) were measured by
      ELISA. Surface expression of ICAM-1 on circulating leukocytes was determined by
      flow cytometry. Enalapril and losartan but not placebo induced a small but stable
      decrease of cICAM-1 and cVCAM-1, while cE-SEL and leukocyte expression of ICAM-1
      remained unchanged. The lowering of plasma adhesion molecules may indicate an
      antiatherogenic effect of angiotensin II blockade in hypercholesterolemia. While
      such preventive effect will have to be proven in clinical trials, our results do
      not support a preference for either enalapril or losartan with regard to their
      possible vasoprotective role.

PMID- 15475832
TI  - Nitric-oxide mediated effects of transdermal capsaicin patches on the ischemic
      threshold in patients with stable coronary disease.
AB  - BACKGROUND: Capsaicin has been shown to exert direct vasodilating effects through
      increased calcitonin gene-related peptide (CGRP) release. However, no data exist
      on its effect following systemic administration in humans. METHODS: Twelve male
      patients with stable coronary disease and a persistently positive exercise were
      selected for study. According to a double blind, placebo-controlled, cross-over
      study, patients were randomized to placebo or 3 g oleic capsaicin-containing
      patches, on 2 different days and with a 2-day interval between treatments.
      Patients performed treadmill exercise testing according to the Bruce protocol.
      Time to 1 mm ST segment depression and to peak exercise, maximal ST segment
      depression, and the number of ECG leads showing diagnostic changes were also
      measured. Blood samples for nitric oxide (NO) and CGRP were drawn at baseline, 2,
      6, and 24 hours after exercise. RESULTS: On placebo, all patients had a positive
      ECG during exercise test. Only 1 patient experienced angina, on both treatments.
      With capsaicin, 1 patient had a negative exercise, while 8 patients significantly
      increased time to 1 mm ST depression from 328 +/- 167 to 401 +/- 174 seconds (P =
      0.01). Of the remaining patients, 1 did not show any changes and 2 showed a worse
      ischemic threshold when on capsaicin. CGRP levels were not significantly
      different between placebo and capsaicin treatment. Conversely, when on capsaicin,
      NO significantly increased at 6 hours. CONCLUSIONS: Transdermal capsaicin may
      improve ischemic threshold in patients with stable coronary disease, probably
      through arteriolar vasodilation. Increased capsaicin-induced NO availability
      could represent the principal mechanism of action.

PMID- 15475833
TI  - Simvastatin acutely reduces myocardial reperfusion injury in vivo by activating
      the phosphatidylinositide 3-kinase/Akt pathway.
AB  - Long-term pretreatment with statins reduces myocardial injury after acute
      ischemia and reperfusion by increasing the expression of endothelial nitric oxide
      synthase (eNOS). We hypothesized that statins may act rapidly enough to protect
      the myocardium from ischemia/reperfusion injury when given right at the beginning
      of the reperfusion period and tried to delineate the role of PI 3-kinase/Akt
      pathway in early eNOS activation. Activated simvastatin was given intravenously 3
      minutes before starting the reperfusion after temporary coronary artery occlusion
      (CAO) in anaesthetized rats. Simvastatin significantly increased myocardial PI 3
      kinase activity, AktSer473, and eNOSSer1177 phosphorylation and reduced infarct
      size by 42%. Infarct size reduction as well as activation of PI 3-kinase/Akt/eNOS
      pathway were not observed in rats co-treated with the PI 3-kinase inhibitor
      wortmannin. Contribution of eNOS was further delineated using the NOS inhibitor L
      NAME, which could completely block cardioprotection by the statin. In summary,
      simvastatin acutely reduces the extent of myocardial necrosis in
      normocholesterolemic rats in an NO- dependent manner by activating the PI 3
      kinase/Akt pathway. This is the first study demonstrating short-term
      cardioprotective effects of simvastatin in an in vivo model of
      ischemia/reperfusion.

PMID- 15475834
TI  - The effect of Ginkgo biloba in isolated ischemic/reperfused rat heart: a link
      between vitamin E preservation and prostaglandin biosynthesis.
AB  - The effect of Ginkgo biloba extract (EGb 761) was studied in rat hearts submitted
      to ischemia/reperfusion. Isolated hearts perfused in Langendorff mode were
      subjected to 60 minutes of global ischemia and 15 minutes of reperfusion. EGb 761
      was administered by chronic or acute treatment: intra-peritoneal injections of 5
      mg/Kg extract for 5 days, or 100 mg /L extract addition to the perfusion buffer,
      respectively. In hearts not treated with EGb 761, ischemia induced a 20% decrease
      in the concentration of membrane alpha-tocopherol. This effect was not worsened
      by reperfusion. alpha-tocopherol consumption was accompanied by about 650%
      increase in 6-ketoPGF1alpha release within 3 minutes of reperfusion. Moreover,
      ischemia induced activation of transcription factor NF-kappaB, as compared with
      the untreated group. In both chronic and acute treatment with EGb 761, heart
      concentration of alpha-tocopherol was completely spared during ischemia as much
      as after reperfusion, and a significant decrease of 6-ketoPGF1alpha release was
      observed at 3 minutes of reperfusion. Nuclear translocation of NF-kappaB was
      lowered during ischemia. EGb 761 might act as direct free radical scavenger or as
      tocopheryl radical recycler; in both cases sparing membrane vitamin E should
      affect phospholipase A2 activity. Finally, EGb 761, by lowering ROS produced
      during ischemia, challenges nuclear translocation of NF-kappaB.

PMID- 15475835
TI  - Urgosedin inhibits hypotension, hypoglycemia, and pro-inflammatory mediators
      induced by lipopolysaccharide.
AB  - Urgosedin is a newly synthesized compound especially with serotonergic and alpha
      adrenergic blocking actions. In rat isolated thoracic aorta, urgosedin
      competitively antagonized norepinephrine-, clonidine-, and serotonin-induced
      vasocontractions in a concentration-dependent manner. In radioligand binding
      experiments, urgosedin had significant binding affinities on alpha1/alpha2, 5
      HT1A, 5-HT1B and 5-HT2A receptors. Intravenous injection of lipopolysaccharide
      (LPS) produced a biphasic hypotension in normotensive rats. Although intravenous
      injection of urgosedin caused minor depressor actions in the normotensive Wistar
      rat, urgosedin significantly attenuated the secondary prolonged hypotension
      produced by LPS. The plasma levels of cytokines (IL-1beta, IL-6, TNF-alpha, and
      IFN-gamma) and hypoglycemia induced by LPS were also reduced by urgosedin.
      Moreover, the acute survival rates (350 minutes) of endotoxic shock increased
      from 0% (LPS group) to 100% in the groups pretreated with urgosedin. In RAW264.7
      cells, urgosedin inhibited LPS-induced inducible nitric oxide synthase (iNOS)
      expression. In conclusion, our data suggest that urgosedin was a newly potent
      serotonergic and mild alpha-adrenergic blocking agent. Its prevention of LPS
      induced hypotension and hypoglycemia might partially mediate through its
      inhibition activities on the iNOS expression and cytokines formation. Urgosedin
      might be an effective pharmacological agent against LPS-induced hypotension,
      hypoglycemia, and the formation of pro-inflammatory mediators.

PMID- 15475836
TI  - Ouabain at nanomolar concentration promotes synthesis and release of angiotensin
      II from the endothelium of the tail vascular bed of spontaneously hypertensive
      rats.
AB  - The effects of 1 nM ouabain (OUA) on the contractile actions of phenylephrine
      (PHE, 0.001-100 microg) and functional activity of the sodium pump (NKA) in
      isolated-perfused tail vascular beds from WKY and SHR were investigated. In
      preparations from SHR, perfusion with OUA in the presence of endothelium (E+)
      increased the sensitivity (pED50) of PHE (before: 2.14 +/- 0.06 versus after:
      2.47 +/- 0.07; P < 0.05) without altering the maximal response (Emax). After
      endothelial damage, OUA reduced the Emax of PHE in SHR (before: 350 +/- 29 versus
      after: 293 +/- 25 mm Hg; P < 0.05). In SHR/E+, pretreatment with losartan (10
      microM) or enalaprilat (1 microM) prevented the increased sensitivity to PHE
      induced by OUA. OUA increased NKA activity in SHR/E+ (before: 45 +/- 6 versus
      after: 58 +/- 5%, P < 0.05). Losartan (10 mg/Kg, i.v.) also abolished the
      increment in systolic and diastolic blood pressure induced by OUA (0.18
      microg/Kg, i.v.) in anesthetized SHR. OUA did not alter the actions of PHE in
      either anesthetized WKY rats or vascular preparations. Results suggest that 1 nM
      OUA increased the vascular reactivity to PHE only in SHR/E+. This effect is
      mediated by OUA-induced activation of endothelial angiotensin converting enzyme
      that promotes the local formation of angiotensin II, which sensitizes the
      vascular smooth muscle to the actions of PHE.

PMID- 15475837
TI  - Ciglitazone inhibits oxidized-low density lipoprotein induced immune maturation
      of dendritic cells.
AB  - BACKGROUND: The peroxisome proliferator-activated receptor (PPAR) activation has
      generally been shown to have anti-inflammatory effects and dendritic cells (DCs)
      are the most efficient antigen presenting cells that play an active role in the
      development of atherosclerosis. The effects of PPARgamma on DCs maturation and
      immune function remain unknown now and we, therefore, studied the influence of
      PPARgamma agonist ciglitazone on the maturation and immune function of DCs.
      METHODS: Human monocytes were purified and immature DCs derived; ciglitazone (25
      micromol/L) was added to the medium for 24 hours; ox-LDL (50 microg/ml) was then
      added to the medium for another 24 hours. The immunophenotypic expressions (CD1a,
      CD40, CD86, and HLA-DR) were analyzed by FACS and endocytosis function by FITC
      dextran and the cytokines secretions of culture supernatants (IL-12,IL
      10,TNFalpha, and IL-2) were measured with ELISA. RESULTS: Ciglitazone reduced ox
      LDL induced immunophenotypic expressions of DCs (CD40, CD1a, and HLA-DR). Ox-LDL
      inhibited the endocytosis of DCs, which was prevented by ciglitazone; ciglitazone
      attenuated ox-LDL induced cytokine secretions of DCs (IL-12, 116 +/- 29 versus 34
      +/- 3 pg/ml*; IL-10, 49 +/- 1 versus 28 +/- 9 pg/ml*; TNFalpha, 46 +/- 16 versus
      24 +/- 8 pg/ml*, *P < 0.05 compared with ox-LDL, respectively). CONCLUSION: Our
      study suggested that one of the anti-inflammatory mechanisms of PPAR-gamma
      agonist ciglitazone was mediated by inhibiting the ox-LDL induced maturation and
      immune function of DCs.

PMID- 15475838
TI  - A comparison between calcium channel blocking drugs with different potencies for
      T- and L-type channels in preventing atrial electrical remodeling.
AB  - Calcium overload plays a key role in the development of atrial electrical
      remodeling. The effect of an L-type Ca channel blocker in preventing this
      remodeling has been reported to be short lasting, partly due to down-regulation
      of this channel and persisting Ca entry through the T-type Ca channel. To prove
      if efonidipine, a dual L- and T-type Ca channel blocker exerts a greater effect
      than an L-type Ca channel blocker verapamil, 21 dogs underwent rapid atrial
      pacing at 400 bpm for 14 days, pretreatment with efonidipine in 7 (E), verapamil
      in 7 (V), and none in 7 (C). We measured the atrial effective refractory period
      (ERP) serially during 14 days of rapid pacing. In response to rapid pacing, ERP
      decreased progressively in C. In contrast, in E and V, ERP remained greater than
      ERP in C (P < 0.01) on days 2 through 7. However, on the 14th day, ERP in V
      decreased to the level seen in C, whereas ERP in E remained significantly longer
      than ERPs in C or V (P < 0.01). The blockade L-type Ca channel alone is not
      sufficient, but the addition of a T-type Ca channel blockade shows a more
      sustained effect to prevent atrial electrical remodeling.

PMID- 15475839
TI  - Mechanisms of impaired vascular response to ANG II in perivascular injured
      carotid arteries of ovariectomized rat.
AB  - The rabbit carotid artery, injured by silicone collar, presents a perivascular
      inflammatory response and alterations in vascular responsiveness. Considering
      that angiotensin II (Ang II) plays an important role in cardiovascular physiology
      and pathology and that cardiovascular disease increases in postmenopausal women,
      the aim of this study was to investigate whether the Ang II contractile response
      in ovariectomized rat carotid artery is modified after a vascular injury by
      silicone collar. The positioning of the silicone collar around the common carotid
      artery for 14 days leads to an increased cross-sectional area of adventitial
      layer with inflammatory cells and an extensive angiogenesis. The Ang II-induced
      contraction was significantly decreased in collared arteries when compared with
      contralateral arteries. The reduction in the constrictor effect of Ang II in
      collared arteries was not modified by the presence of indomethacin (a non
      selective inhibitor of cyclooxygenase) or PD 123,319 (a selective antagonist of
      the Ang II AT2 receptor). Moreover, while endothelium removal induced an increase
      in the Ang II responsiveness of both arteries (collared and contralateral), the
      Emax induced by Ang II was still lower in collared arteries. However, the "in
      vitro" pretreatment of the arteries with an inhibitor of nitric oxide synthase
      enzyme (L-NAME) significantly enhanced the maximal contractions response to Ang
      II only in injured arteries. Furthermore, the expression of iNOS (inducible
      nitric oxide synthase) was observed in the adventitial layer of collared
      arteries, indicating that the NO formed in the adventitial layer has an important
      role in injured arteries. Moreover, our data show impairment of extracellular
      calcium mobilization, mediated by Ang II, in the collared artery, although the
      intracellular calcium mobilization was not modified by the injury. In conclusion,
      the increased production of NO and a decrease in the calcium influx displayed by
      Ang II in the collared artery appears to counteract and reduce the biologic
      effect of Ang II.

PMID- 15475841
TI  - When evolution Begets revolution.

PMID- 15475840
TI  - Antihypertensive treatment and renal damage: amlodipine exerts protective effect
      through the polyol pathway.
AB  - Besides generating renal damage, hypertension plays an important role in the
      progression of diabetic nephropathy. The fructose-fed rat is a well-established
      model both of high blood pressure and renal impairment, which is similar to
      diabetic nephropathy. To clarify the relationship between hypertension, glucose
      metabolism, and kidney remodeling, we investigated the renal level of Glut 1 and
      Glut 5, their relation to fibrosis and the effects of an antihypertensive drug on
      renal damage. Twenty-four male WK rats were divided into three groups: 8 animals
      received a fructose-enriched diet, 8 a control diet, and 8 animals a high
      fructose diet plus amlodipine (5 mg/Kg). After six weeks of treatment, we
      observed a significant increase in Glut 5, fibronectin, and sorbitol in fructose
      fed rats compared with control and amlodipine-treated animals; there was a
      positive correlation between Glut 5 and fibronectin levels (r = 0.63). Glut 1
      levels were similar in all three groups, whereas collagen IV was higher in
      fructose-fed rats; amlodipine prevented the increase of collagen IV and sorbitol.
      Collagen I was statistically higher in the fructose group than in the other two
      groups. Therefore, prolonged fructose feeding results in renal fibrosis via
      polyol pathway overactivity that can be prevented by means of an antihypertensive
      drug.

PMID- 15475842
TI  - Locked internal fixator: sensitivity of screw/plate stability to the correct
      insertion angle of the screw.
AB  - OBJECTIVE: Internal fixators with angular stability have been developed to
      provide high stability without compression of the plate on to the bone. Angular
      and axial stability of a plate-screw construct can be achieved using a conically
      threaded screw head undersurface and a corresponding conically threaded plate
      hole. Furthermore, the insertion angle of the screw must correspond precisely to
      the axis of the screw hole. This is not always achieved in clinical practice and
      may result in screw loosening. The objective of this study was to examine the
      relationship between the stability of the locked screw-plate on the insertion
      angle of the screw. METHODS: Locking screws were inserted in an isolated (Point
      Contact Fixator, PC-Fix) or combined (Locking Compression Plate, LCP 4.5) locking
      hole with the use of an aiming device. The optimal insertion angle for these
      plates is perpendicular to the plate surface. The screws were inserted with an
      axis deviation of 0 degrees (optimal condition), 5 degrees , and 10 degrees
      respective to the optimal angle (variance +/- 1 degrees ). The samples were
      tested under shear or axial (push out) loading conditions until failure occurred.
      An Instron materials testing machine was used. RESULTS: Locking screws inserted
      in the isolated locking hole (PC-Fix) showed a significant decrease of failure
      load if inserted at 5 degrees and 10 degrees angle. Using an optimal insertion
      angle (0 degrees ), failure load was 1480 +/- 390 N, with 5 degrees axis
      deviation 780 +/- 160 N, P = 0.0001, and with 10 degrees axis deviation 550 +/-
      110 N, P = 0.0001. Screws inserted in the combined locking hole (LCP) also showed
      a significant decrease of push-out force of 77% (4960 +/- 1000 N versus 1120 +/-
      400 N) with 10 degrees axis deviation. Compared to optimal insertion angle (0
      degrees ), bending load to failure did decrease up to 69% (1240 +/- 210 N vs. 390
      +/- 100 N) with 10 degrees axis deviation. CONCLUSION: A locking head screw
      exhibits high stability with a moderate axis deviation in the angle of insertion
      of up to 5 degrees . However, there is a significant decrease in stability with
      increasing axis deviation (>5 degrees ). An aiming device is recommended to
      provide optimal fixation with angular stability.

PMID- 15475843
TI  - Biomechanics of locked plates and screws.
AB  - OBJECTIVE: To review the biomechanical principles that guide fracture fixation
      with plates and screws; specifically to compare and contrast the function and
      roles of conventional unlocked plates to locked plates in fracture fixation. We
      review basic plate and screw function, discuss the design rationale for the new
      implants, and examine the biomechanical evidence that supports the use of such
      implants. DATA SOURCES: Systematic review of the per reviewed English language
      orthopaedic literature listed on PubMed (National Library of Medicine online
      service). STUDY SELECTION: Papers selected for this review were drawn from peer
      review orthopaedic journals. All selected papers specifically discussed plate and
      screw biomechanics with regard to fracture fixation. PubMed search terms were:
      plates and screws, biomechanics, locked plates, PC-Fix, LISS, LCP, MIPO, and
      fracture fixation. DATA SYNTHESIS: The following topics are discussed: plate and
      screw function-neutralization plates and buttress plates, bridge plates; fracture
      stability-specifically how this effects gap strain and fracture union,
      conventional plate biomechanics, and locking plate biomechanics. CONCLUSIONS:
      Locked plates and conventional plates rely on completely different mechanical
      principles to provide fracture fixation and in so doing they provide different
      biological environments for healing. Locked plates may increasingly be indicated
      for indirect fracture reduction, diaphyseal/metaphyseal fractures in osteoporotic
      bone, bridging severely comminuted fractures, and the plating of fractures where
      anatomical constraints prevent plating on the tension side of the bone.
      Conventional plates may continue to be the fixation method of choice for
      periarticular fractures which demand perfect anatomical reduction and to certain
      types of nonunions which require increased stability for union.

PMID- 15475844
TI  - Biomechanical evaluation of the less invasive stabilization system, angled blade
      plate, and retrograde intramedullary nail for the internal fixation of distal
      femur fractures.
AB  - OBJECTIVE: To evaluate the stability of the retrograde intramedullary nail (IMN),
      angled blade plate (ABP), and a locked internal fixator (Less Invasive
      Stabilization System [LISS], Synthes, Paoli, PA) for internal fixation of distal
      femur fractures. DESIGN: Destructive biomechanical testing of matched pairs of
      fresh-frozen human cadaveric bone-implant constructs. SETTING: Biomechanical
      laboratory. METHODS: A fracture model was created to simulate an AO/OTA33-A3
      fracture. Forty-eight matched pairs of specimens were used. Six groups of 8 pairs
      each were tested to failure: LISS versus ABP and LISS versus IMN (axial,
      torsional, and cyclical axial). MAIN OUTCOME MEASUREMENT: Load to failure, mode
      of failure, energy to failure, displacement at the load to failure, and
      stiffness. RESULTS: Fixation strength (load/moment to failure) of the LISS
      constructs was 34% greater in axial loading (P = 0.01) and 32% less in torsional
      loading (P = 0.05) compared with ABP constructs and 13% greater in axial loading
      (P = 0.35) and 45% less in torsional loading (P < 0.01) compared with IMN
      constructs. Loss of distal fixation in axial loading occurred in 1 of 16 cases
      with the LISS, in 3 of 8 cases with the ABP, and in 8 of 8 cases with the IMN.
      Cyclical axial loading demonstrated significantly less plastic deformation for
      the LISS construct compared with ABP constructs (P < 0.01) and similar plastic
      deformation compared with IMN constructs (P = 0.98). CONCLUSIONS: All 3 fixation
      devices (LISS, ABP, and IMN) offer sufficient torsional stability and sufficient
      proximal fixation that withstands axial loading without failing. The LISS
      provides improved distal fixation, especially in osteoporotic bone, at the
      expense of more displacement at the fracture site.

PMID- 15475845
TI  - Early results of the less invasive stabilization system for mechanically unstable
      fractures of the distal femur (AO/OTA types A2, A3, C2, and C3).
AB  - OBJECTIVES: Historically, mechanically unstable fractures of the distal femur
      have been difficult to treat. Problems such as varus collapse, malunion, and
      nonunion frequently resulted before fixed-angle plates and indirect reduction
      techniques were popularized. More recently, the Less Invasive Stabilization
      System, or LISS (Synthes, Paoli, PA), has been designed to combine these 2
      approaches with the intended goals of achieving adequate stable fixation and
      early healing. Early clinical results for the femoral Less Invasive Stabilization
      System have been promising. The purpose of this study is to evaluate the clinical
      results of patients with high energy, mechanically unstable fractures of the
      distal femur treated with the Less Invasive Stabilization System. DESIGN:
      Retrospective analysis of a treatment protocol, consecutive patient series.
      SETTING: Busy level II trauma center. PATIENTS /PARTICIPANTS: Twenty-six patients
      with 27 high-energy AO/OTA types A2, A3, C2, and C3 fractures of the distal
      femur. INTERVENTION: Treatment with indirect fracture reduction and internal
      distal femoral fixation using the Less Invasive Stabilization System. MAIN
      OUTCOME MEASUREMENTS: Clinical and radiographic assessment. RESULTS: Twenty-one
      patients with 22 fractures were available for evaluation at an average 19 months
      postinjury (range 12-35 months). The mechanism of injury included 12 motor
      vehicle collisions, 4 high falls, 5 motorcycle crashes, and 1 bicyclist struck by
      a car. Twenty patients had associated injuries. Six fractures were open. All
      fractures were comminuted; according to the AO/OTA fracture classification there
      were 4 A2, 3 A3, 12 C2, and 3 C3 fractures. All fractures healed without
      secondary surgeries at a mean of 13 weeks (range 7-16 weeks). There were no cases
      of failed fixation, implant breakage, or infection. Average joint line
      orientation relative to the femoral shaft axis (valgus) measured 99 degrees on
      postoperative radiographs and 99 degrees on final radiographs. A comparison of
      postoperative to healed final radiographs for each femur demonstrated no case
      with greater than a 3 degrees difference in either varus or valgus. Complications
      included 1 mal-union where the fracture was fixed in 8 degrees of valgus and 2
      cases of external rotation between 10 degrees and 15 degrees. Painful hardware
      occurred in 4 patients, of which 3 underwent implant removal. The average knee
      range of motion was 5 degrees to 114 degrees. CONCLUSIONS: The Less Invasive
      Stabilization System allows for stable fixation and facilitates early healing in
      mechanically unstable high-energy fractures of the distal femur. There were no
      patients with fixation failure, varus collapse, or nonunion in this "at-risk"
      population. This treatment safely allows for immediate postoperative initiation
      of joint mobility and the progression of weight bearing with early radiographic
      signs of healing.

PMID- 15475846
TI  - Treatment of distal femur fractures using the less invasive stabilization system:
      surgical experience and early clinical results in 103 fractures.
AB  - OBJECTIVE: To summarize the complications and early clinical results of 123
      distal femur fractures treated with the Less Invasive Stabilization System (LISS;
      Synthes, Paoli, PA). DESIGN: Retrospective analysis of prospectively enrolled
      patients. SETTING: Two academic level I trauma centers. SUBJECTS AND
      PARTICIPANTS: One hundred nineteen consecutive patients with 123 distal femur
      fractures (OTA type 33 and distal type 32 fractures) treated by 3 surgeons. One
      hundred three fractures (68 closed fractures and 35 open fractures) in 99
      patients were followed up at least until union (mean follow-up = 14 months,
      range: 3-50 months). INTERVENTION: Surgical reduction and fixation of distal
      femur fractures. MAIN OUTCOME MEASUREMENTS: Perioperative complications,
      radiographic union, infection rate, loss of fixation, alignment, and range of
      motion. RESULTS: Ninety-six (93%) of 103 fractures healed without bone grafting.
      All fractures eventually healed with secondary procedures, including bone
      grafting (1 of 68 closed fractures and 6 of 35 open fractures). There were 5
      losses of proximal fixation, 2 nonunions, and 3 acute infections. No cases of
      varus collapse or screw loosening in the distal femoral fragment were observed.
      Malreductions of the femoral fracture were seen in 6 fractures (6%). The mean
      range of knee motion was 1 degrees to 109 degrees . CONCLUSIONS: Treatment of
      distal femur fractures with the LISS is associated with high union rates without
      autogenous bone grafting (93%), a low incidence of infection (3%), and
      maintenance of distal femoral fixation (100%). No loss of fixation in the distal
      femoral condyles was observed despite the treatment of 30 patients older than 65
      years. The LISS is an acceptable surgical option for treatment of distal femoral
      fractures.

PMID- 15475847
TI  - Treatment of complex proximal tibia fractures with the less invasive skeletal
      stabilization system.
AB  - OBJECTIVE: Proximal tibia fractures with metaphyseal comminution present a
      difficult treatment challenge. The Less Invasive Skeletal Stabilization (LISS)
      internal fixator system has theoretical advantages (minimally invasive fixed
      angle construct) for the treatment of these injuries. This report presents
      clinical results of the LISS system for treatment of complex proximal tibia
      fractures and illustrates the unique properties of the system. DESIGN:
      Prospective clinical trial. SETTING: Level I trauma center. PATIENTS: Twenty
      eight consecutive patients with comminuted proximal tibia metaphyseal fractures
      (41A3, 41C2, or 41C3) treated with LISS plates. OUTCOME MEASUREMENTS: Healing,
      fracture alignment, infectious and implant-related complications, and functional
      outcome based on the Lower Extremity Measure (LEM). RESULTS: Average follow-up
      was 23 months (range 12-48). Thirty-seven of 38 patients healed their fracture
      after the index procedure. The other healed after implant removal without the
      need for further fracture repair. Postoperative fracture alignment was
      satisfactory in 37 of the 38 cases and was maintained in all patients at union.
      There were no infectious complications. The average LEM score was 88.
      CONCLUSIONS: The LISS internal fixator system can be used successfully to treat
      complex proximal tibia fractures without the need for additional medial
      stabilization. Surgeons attempting to use fixed angle internal fixation plating
      systems should familiarize themselves with the significant technical differences
      between these and traditional plating systems to assure satisfactory results.

PMID- 15475848
TI  - Treatment of proximal tibia fractures using the less invasive stabilization
      system: surgical experience and early clinical results in 77 fractures.
AB  - OBJECTIVE: To summarize the surgical experience and clinical results of the first
      89 fractures of the proximal tibia treated with the Less Invasive Stabilization
      System (LISS; Synthes, Paoli, PA). DESIGN: Retrospective analysis of
      prospectively enrolled patients into a database. SETTING: Academic level I trauma
      center. SUBJECTS/PARTICIPANTS: Eighty-seven consecutive patients with 89 proximal
      tibia fractures (AO/OTA type 41 and proximal type 42 fractures) treated by 2
      surgeons. Seventy-five patients with 77 fractures were followed until union. The
      mean follow-up was 14 months (range: 3-35 months). There were 55 closed fractures
      and 22 open fractures. INTERVENTION: Surgical reduction and fixation of
      fractures, followed by rehabilitation. MAIN OUTCOME MEASUREMENTS: Perioperative
      and postoperative complications, postoperative alignment, loss of fixation, time
      to full weight bearing, radiographic union, and range of motion. RESULTS: Seventy
      of 77 fractures healed without major complications (91%). There were 2 early
      losses of proximal fixation, 2 nonunions, 2 deep delayed infections, and 1 deep
      peroneal nerve palsy. Other complications included a superficial wound infection
      and 3 seromas. Postoperative malalignment occurred in 7 patients with 6 degrees
      to 10 degrees of angular deformity (6 flexion/extension and 1 varus/valgus
      malalignments), and an eighth patient had a 15 degrees flexion deformity. In 4
      patients, the hardware was removed at an average of 13 months because of
      irritation (5%). The mean time for allowance of full weight bearing was 12.6
      weeks (range: 6-21 weeks), and the mean range of final knee motion was 1 degrees
      to 122 degrees . CONCLUSIONS: The LISS provides stable fixation (97%), a high
      rate of union (97%), and a low (4%) rate of infection for proximal tibial
      fractures. The technique requires the successful use of new and unfamiliar
      surgical principles to effect an accurate reduction and acceptable rate of
      malalignment.

PMID- 15475849
TI  - Anatomy of the superficial peroneal nerve in relation to fixation of tibia
      fractures with the less invasive stabilization system.
AB  - OBJECTIVE: To examine the danger to the superficial peroneal nerve during
      percutaneous screw placement in the distal holes of the 13-hole proximal tibia
      Less Invasive Stabilization System plate in a cadaver. DESIGN: Anatomic study.
      SETTING: Medical school anatomy laboratory. INTERVENTIONS: Fourteen adult
      cadaveric lower extremities were used. A 13-hole proximal tibia Less Invasive
      Stabilization System plate was placed as described by the manufacturer.
      Dissection of the superficial peroneal nerve was performed following localization
      of screw holes 7 through 13 using insertion sleeves, centering sleeves, and 2.0
      mm Kirschner wires passed through the insertion guide. RESULTS: The average
      distance from the superficial peroneal nerve to the center of holes 11, 12, and
      13 was 10.0 mm (range 0-21, standard deviation 5.6), 6.8 mm (range 0-16, standard
      deviation 4.3), and 2.7 mm (0-11, standard deviation 3.7), respectively. In 12 of
      14 legs (86%), the superficial peroneal nerve was 5.0 mm or less from the center
      of hole 13. The nerve was touching the guide wire at hole 11 in 1 specimen (7%),
      at hole 12 in 2 specimens (14%), and at hole 13 in 6 specimens (43%). In 1
      specimen (7%), the guide wire pierced the superficial peroneal nerve at hole 13.
      CONCLUSION: These findings suggest that the superficial peroneal nerve is at
      significant risk during percutaneous screw placement in holes 11 through 13 of
      the 13-hole proximal tibia Less Invasive Stabilization System plate. Use of a
      larger incision and careful dissection down to the plate in this region may
      minimize the risk of damage to the nerve.

PMID- 15475850
TI  - Unstable proximal extraarticular tibia fractures: a biomechanical evaluation of
      four methods of fixation.
AB  - OBJECTIVE: To compare the biomechanical stability of extraarticular proximal
      tibia fractures reconstructed using a double-plate construct, locking plate
      system, hybrid external fixator, and single lateral periarticular plate, all from
      the same manufacturer. DESIGN: Standardized proximal tibial fractures (AO
      classification 41-A3.2 and A3.3) in synthetic tibiae were stabilized using one of
      the four constructs. Load versus proximal fragment translation and rotation were
      monitored in each case. Fixation was evaluated for moderately unstable and
      completely unstable fractures simulated by wedge and gap osteotomies of the
      proximal femur. SETTING: Academic medical center biomechanical engineering
      laboratory. MAIN OUTCOME MEASUREMENTS: Proximal fragment axial displacement,
      varus rotation, and posterior rotation versus applied load for each of the
      constructs. RESULTS: The double-plate construct was significantly stiffer than
      all other constructs with regard to resistance to axial displacement, varus
      rotation, and posterior rotation for both types of unstable fractures. With
      regard to axial stiffness, the double-plate construct was statistically similar
      to an intact tibia for moderately stable fractures. The locking plate and the
      external fixator were similar for stabilization of moderately unstable fractures,
      whereas the locking plate and the periarticular plate were significantly stiffer
      than the external fixator construct for completely unstable fractures.
      CONCLUSION: For axial load applied to a wedge or gap osteotomy of the proximal
      tibia, the double-plate construct provided significantly more rigidity than the
      other constructs. The locking plate, periarticular plate, and hybrid external
      fixator tested provided similar rigidity for the wedge osteotomy, but for the gap
      osteotomy the external fixator could not support 600N without complete closure of
      the gap.

PMID- 15475851
TI  - Less invasive stabilization of complex tibial plateau fractures: a biomechanical
      evaluation of a unilateral locked screw plate and double plating.
AB  - OBJECTIVE: To compare the vertical subsidence in a bicondylar tibial plateau
      fracture model stabilized either by a unilateral locked screw plate (LSP) or by
      double plating. DESIGN: Biomechanical cadaver study. INTERVENTION: A 41-C1
      fracture model was created in eight pairs of fresh-frozen human cadaver tibiae.
      Stabilization was performed either by open reduction and internal fixation (ORIF)
      using a lateral L-buttress plate and a medial four-hole, one-third tubular
      antiglide-plate or by a lateral LSP. Four load levels (400N, 800N, 1200N, 1600N),
      each with five cycles, were consecutively applied to the medial plateau. MAIN
      OUTCOME MEASUREMENTS: The vertical plastic deformation at the end of each cycle
      was the main parameter of interest. Statistical analysis was performed with the
      two-way ANOVA test for repeated measurements. Each individual loading level was
      analyzed separately using Student t test. RESULTS: In one pair, both fixation
      techniques failed at the first loading cycle of 1200N. One ORIF fixation failed
      at the first loading cycle of 1600N. The average plastic vertical subsidence was
      0.40 mm (LSP) and 0.25 mm (ORIF) at 400N (P = 0.291), 0.83 mm (LSP) and 0.81 mm
      (ORIF) at 800N (P = 8.82), 1.06 mm (LSP) and 0.96 mm (ORIF) at 1200N (P = 0.98),
      and 1.54 mm (LSP) and 1.14 mm (ORIF) at 1600N (P = 0.53). Vertical subsidence
      depended on the applied load (P = 0.002), but not on the method of fixation (P =
      0.236). CONCLUSION: Both fixation techniques have a high resistance to vertical
      subsidence even with loads exceeding the average body weight. No statistically
      significant difference was seen between the two methods of fixation.

PMID- 15475852
TI  - The less invasive stabilization system in the treatment of complex fractures of
      the tibial plateau: short-term results.
AB  - OBJECTIVES: To report on the use of a new plating system in the treatment of high
      energy tibial plateau fractures using minimally invasive stabilization
      techniques. DESIGN: Prospective, consecutive patient series. SETTING: University
      Level I trauma center. PATIENTS: Thirty-seven patients with 39 fractures of the
      tibial plateau were treated using specialty plates. All fractures were OTA class
      41C. Ten of the fractures were open, including eight Gustilo and Anderson Type
      IIIA and two Type IIIB. Thirty-three patients with 34 fractures had follow-up of
      at least 12 months. INTERVENTION: Internal fixation with the Less Invasive
      Stabilization System (LISS, Synthes USA, Paoli, PA) using minimally invasive
      techniques. MAIN OUTCOME MANAGEMENT: To determine clinical outcome, time to
      union, fracture alignment, articular step-off, incidence of complications, Short
      Form-36 outcome scores, and Lysholm knee scores in patients with associated
      ligament injuries. RESULTS: All 34 of the fractures healed without additional
      surgical intervention or bone grafting. The mean follow-up in our series was 21
      months, with a range of 12 to 38 months. Twenty-nine patients with 30 fractures
      had follow-up of greater than 1 year. The average time to radiographic callus was
      6.1 weeks, and the average time to complete union was 15.6 weeks. The articular
      step-off average was 0.8 mm, with a range of 0 to 5 mm. The postoperative
      alignment demonstrated 1 patient with a malalignment of 5 degrees procurvatum and
      1 patient with 4 degrees of valgus. There were two superficial wound infections
      and no cases of deep infection or osteomyelitis. CONCLUSIONS: The use of LISS
      plates appears to stabilize complex fractures of the tibial plateau with a low
      incidence of complications. The LISS system functioned well in maintaining
      alignment and obtaining union in these high-energy fractures.

PMID- 15475853
TI  - Preliminary stabilization of the less invasive stabilization system.
AB  - We describe the use of a universal T-handle chuck to provide preliminary
      stabilization of the Less Invasive Stabilization System supracondylar femur
      implant and aiming device. This technique is helpful to maintain the position of
      the plate against the bone during intraoperative radiographs and initial screw
      insertion. Use of this simple technique may help avoid the problems that occur
      when the plate is positioned too far away from the lateral femoral cortex.

PMID- 15475854
TI  - Removal of the less invasive stabilization system.
AB  - The Less Invasive Stabilization System (LISS; Synthes; Paoli, PA) is a newly
      developed locking plate that has been used for fixation of distal femoral
      supracondylar and proximal tibial fractures. The early clinical results have been
      encouraging; however, there is little information available on the removal of
      these implants. Frequent stripping of the locking screws has been found by our
      group when removal is attempted. Our approach to this problem is described.

PMID- 15475855
TI  - Failure of less invasive stabilization system plates in the distal femur: a
      report of four cases.
AB  - Four cases of failure of distal femoral Less Invasive Stabilization System plates
      are reported. Two modes of failure were observed: in 2 cases, the Less Invasive
      Stabilization System plates broke, and in 2 cases, the plates gradually displaced
      from the femur as the shaft screws lost purchase in the diaphyseal femoral
      cortex. Delayed union/nonunion, early weight bearing, and improper plate
      placement were identified as the etiologies for plate failure.

PMID- 15475856
TI  - Locking compression plate loosening and plate breakage: a report of four cases.
AB  - The Locking Compression Plate (LCP) system offers a number of advantages in
      fracture fixation combining angular stability through the use of locking screws
      with traditional fixation techniques. This makes the implant particularly
      suitable for use in poor bone stock and complex joint fractures, especially in
      the epimetaphyseal area. However, the system is complex, requiring careful
      attention to biomechanical principles, and a number of potential pitfalls need to
      be considered. These pitfalls are illustrated in the 4 cases described herein, in
      which treatment was unsuccessful due to implant breakage or loosening. In each
      case, treatment failure could be attributed to the choice of an inappropriate
      plate and/or fixation technique, rather than to the features of the Locking
      Compression Plate system itself. Such experiences highlight the importance of
      detailed understanding of the biomechanical principles of plate fixation as well
      as careful preoperative planning for the successful use of the Locking
      Compression Plate system.

PMID- 15475871
TI  - Atypical antipsychotics: matching receptor profile to individual patient's
      clinical profile.
AB  - Understanding common pharmacologic and clinical "class" actions associated with
      atypical antipsychotics certainly reveals how these agents are alike, but what
      about unique differences from one agent to another? Atypical antipsychotics are
      also a heterogeneous group of agents that have complex pharmacologic entities,
      acting upon multiple dopamine receptors (D2, D1, D3, and D4) and multiple
      serotonin receptors (5-HT2A, 5-HT2C, 5-HT1A, and 5-HT1D, among others). Atypical
      antipsychotics also interact with noradrenergic (alpha 1- and alpha 2-adrenergic
      receptor blockade), histaminergic (H1-receptor blockade), and cholinergic
      (muscarinic M1 blockade) neurotransmitter systems as well as with monoamine (D, 5
      HT, and norepinephrine reuptake blockade) transporters. However, no two atypical
      antipsychotics possess the same portfolio of actions upon all of these additional
      neurotransmitter systems.

PMID- 15475873
TI  - Cognitive factors in schizophrenia: causes, impact, and treatment.
AB  - Greater attention has been given to the cognitive dimension in schizophrenia in
      recent years. This has resulted from increased recognition that cognitive
      impairment and negative symptoms of the disease have a greater impact on quality
      of life (QOL) compared to positive symptoms. Successful treatment of positive
      symptoms in patients with schizophrenia has not been shown to robustly translate
      into improvements in employment status or social relationships, while cognitive
      improvements are strongly associated with these important aspects of QOL and
      independence. These findings are based on extensive testing with standard
      cognitive tests for measuring executive function, verbal learning and memory,
      word recall, verbal working memory, spatial working memory, attention, and
      vigilance. Verbal learning and executive function, in particular, have been found
      to be valid predictors of employment success independent of the degree of
      severity of positive symptoms.

PMID- 15475874
TI  - Treating the mind and body in schizophrenia: risks and prevention.
AB  - Patients with schizophrenia have increased mortality due to higher rates of
      suicide. However, natural causes of death, such as cardiovascular disease, also
      contribute greatly to excess mortality. Significant sources of cardiovascular
      risk in this patient population include high smoking prevalence, inactive
      lifestyles, poor dietary habits, and the metabolic effects of atypical
      antipsychotics. These sources of risk interact with underrecognition of common
      medical conditions by mental health providers, limited access to primary care
      services, and undertreatment of health conditions in the general medical setting.
      For many patient with severe mental illness, the mental health setting represents
      the sole source of medical care, making the psychiatrist the de facto primary
      care provider for these individuals. With the recent focus on medical
      consequences of antipsychotic treatment, psychiatrist have an obligation to
      minimize these adverse effects by choosing antipsychotics with lower risk for
      metabolic side effects, and becoming familiar with the screening and management
      of common medical conditions.

PMID- 15475875
TI  - Maximizing function after first-episode psychosis.
AB  - Interest in early and preventive interventions in patients with psychotic
      disorders has increased over the past few years as a result of the intuitive
      appeal of such interventions. Results of studies point to an association between
      longer duration of untreated psychosis and poor outcome, atypical antipsychotic
      agents less likely to cause extrapyramidal side effects, and a shift from
      hospital to community-based care for many patients with severe mental illness.
      Treatment strategies specifically directed to first-episode psychosis may help to
      improve outcomes. Such strategies include the use of lower doses of antipsychotic
      medications, the predominant use of atypical antipsychotic agents, and the
      deployment of psychological interventions that address the unique needs of young,
      first-episode patients and their families.

PMID- 15475877
TI  - Mutation spectrum of the CYP1B1 gene in Indian primary congenital glaucoma
      patients.
AB  - PURPOSE: The human Cytochrome P450 gene CYP1B1 has been implicated in primary
      congenital glaucoma worldwide. The aim of this study was to understand the role
      of CYP1B1 mutations in causing primary congenital glaucoma in Indian populations.
      METHODS: The study included 64 new and unrelated cases of primary congenital
      glaucoma from different ethnic groups of India. Direct sequencing screened the
      coding and the promoter regions of CYP1B1. RESULTS: Sixteen pathogenic mutations
      were observed in 24 cases, of which 7 were novel. These included two frameshift
      mutations leading to deletions of 23 bp (g.3905del23bp) and 2 bp (g.7900
      7901delCG) in exons II and III, respectively. Four novel missense mutations viz.
      A115P, M132R, Q144P, S239R were noted in exon II, and one in exon III (G466D),
      whose residue is a part of the "signature sequence" (NH2-FXXGXXXCXG-COOH) and is
      present in all heme binding cytochromes. Overall, CYP1B1 was involved in 37.50%
      (24/64) cases and homozygosity of the mutant allele was seen in 29.68% (19/64)
      and compound heterozygosity in 3.12% (2/64) of the cases, respectively. The
      frequency of CYP1B1 mutations was comparatively lower than Saudi Arabian,
      Slovakian Gypsys, and Turkish populations, largely due to genetic heterogeneity
      and ethnic diversities in Indian populations. Genotype-phenotype correlation
      indicated variable prognosis that could be due to the type of mutation, leading
      to alteration of CYP1B1 protein. CONCLUSIONS: This study provides a mutation
      spectrum of CYP1B1 causing primary congenital glaucoma in Indian populations that
      has implications in devising molecular diagnostics for rapid screening.

PMID- 15475878
TI  - RNA interference targeting transforming growth factor-beta type II receptor
      suppresses ocular inflammation and fibrosis.
AB  - PURPOSE: Transforming growth factor-beta(TGF-beta) is an important mediator of
      wound healing responses. In the eye, TGF-beta activity has been implicated in
      causing corneal haze after laser surgery and subconjunctival scarring following
      glaucoma surgery. The purpose of the study was to determine whether small
      interference RNAs (siRNAs) targeting the type II receptor of TGF-beta (TbetaRII)
      could be used to suppress the TGF-beta action. METHODS: TbetaRII specific siRNAs
      designed from the human gene sequence were transfected into cultured human
      corneal fibroblasts. The protein and transcript levels of the receptor were
      determined by immunofluorescence, western blotting, and real time PCR.
      Immunofluorescence and immunoblotting were carried out to examine fibronectin
      assembly. A wound closure assay was used to assess cell migration in in vitro
      fibroblast cultures. In addition, the in vivo effects of TbetaRII siRNA were
      evaluated in a mouse model of ocular inflammation and fibrosis generated by
      subconjunctival injection of phosphate buffered saline and latex beads. Mouse
      TbetaRII siRNA was introduced into experimental eyes. Cellularity on tissue
      sections was evaluated after staining with hematoxylin and eosin. Collagen
      deposition was visualized by picrosirius red staining. RESULTS: TbetaRII siRNAs
      abrogated the receptor transcript and protein expression in cultured corneal
      fibroblasts. The gene knockdown inhibited fibronectin assembly and retarded cell
      migration. In the mouse model, introduction of TbetaRII specific siRNA
      significantly reduced the inflammatory response and matrix deposition.
      CONCLUSIONS: TbetaRII specific siRNAs were efficacious both in vitro and in vivo
      in knocking down the TGF-beta action. A direct application of siRNA into eyes to
      downregulate TbetaRII expression may provide a novel therapy for preventing
      ocular inflammation and scarring.

PMID- 15475881
TI  - Medicines for vegetarians.

PMID- 15475879
TI  - Effects of ectopic decorin in modulating intracranial glioma progression in vivo,
      in a rat syngeneic model.
AB  - Given the failure of conventional treatments for glioblastoma, gene therapy has
      gained interest considerable in recent years. Gliomas are associated with a state
      of immunosuppression, which appears to be partially mediated by an increase in
      secretion of transforming growth factor-beta (TGF-beta) from glioma cells.
      Decorin, a small proteoglycan which can bind to and inactivate TGF-beta, has been
      successfully used as an antitumor strategy on stably transfected tumor cells and
      has been shown to cause growth suppression in neoplastic cells of various
      histological origins. In this paper, we investigated the use of gene therapy to
      deliver the decorin transgene in a site-specific manner in an experimental model
      of intracranial gliomas. Our aim was to inhibit the glioma-associated
      immunosuppressive state, and prolong the survival of tumor-bearing rats. We
      studied the effects of decorin gene transfer in the rat CNS-1 glioma model. To
      assess the effect of ectopic expression of decorin on glioma progression in vivo,
      stably transfected CNS-1 cells expressing decorin were implanted into the brain
      parenchyma of syngeneic Lewis rats. The rats implanted with CNS-1 cells
      expressing decorin survived significantly longer than those in the control groups
      which received CNS-1 cells that did not express decorin (P < .0001). We then
      investigated whether the survival observed with decorin expressing cells could be
      mimicked in vivo, using recombinant adenoviruses (RAds) expressing the decorin
      gene under the control of two different promoters: the human immediate-early
      cytomegalovirus (h-IE-CMV) and the glial fibrillary acidic protein (GFAP). In
      vivo results showed that administration of RAd expressing the human decorin under
      the control of h-IE-CMV promoter has a small, but significant effect in
      prolonging the survival of experimental tumor bearing rats (P < .0001). Our data
      indicate that ectopic decorin expression has the potential to slow glioma
      progression in vivo. Our results also indicate that expression of decorin has to
      be present in all cells which constitute the intracranial tumor mass for the
      inhibition of tumor growth and prolongation of the life expectancy of tumor
      bearing rats to be effective.

PMID- 15475882
TI  - Referral letters.

PMID- 15475884
TI  - NICE guidelines.

PMID- 15475893
TI  - Endodontics: part 4. Morphology of the root canal system.

PMID- 15475894
TI  - Eruptive tooth movement--the current state of knowledge.
AB  - How the dentition erupts, and what controls it, is fundamental to almost all
      aspects of clinical dentistry, yet the mechanisms behind this have not yet been
      fully elucidated. When the process continues into space that has been created
      through toothwear or tooth loss, problems in placing restorations can be
      encountered. This review examines the possible mechanisms of tooth eruption.
      Differences between processes in animals and humans are highlighted. The
      limitations of conclusions drawn from animal studies are then discussed with
      reference to human dental conditions. The differing forms of overeruption in
      humans are described and the treatment options for overerupted teeth, including
      prevention of the situation arising, are provided with a discussion of the
      quality of the evidence base behind these.

PMID- 15475902
TI  - The prevalence and nature of recent self-reported changes in general dental
      practice in a sample of English general dental practitioners.
AB  - OBJECTIVE: To determine the extent and types of change in seven domains of dental
      practice in a sample of English general dental practitioners (GDPs). METHODS: A
      postal questionnaire was sent to 561 GDPs on the dental lists of three health
      authorities in diverse regions of England. Information collected included
      demographic details on personal and practice characteristics, self-rating of
      amount of change in the seven domains of practice and factors influencing change.
      RESULTS: The response rate was 60%. Fifty-six per cent of the sample were under
      40 years old. Over a third of respondents reported "changing a lot or completely"
      certain clinical activities, practice management arrangements and practice
      amenities. The highest self-reported level of change was in clinical activities.
      Of the GDPs who reported changing their clinical activities, 56% reported an
      increase in preventive care, followed by crown and bridge (44%), periodontics
      (44%) and endodontics (43%). Practice management rated second in the mean rank
      scores for self-reported change. The main changes reported were the introduction
      of computer systems and employment of practice managers. A sizeable percentage
      (66%) reported increasing the amount of information they provided to patients and
      the time spent discussing care. Quality assurance activities were the area of
      practice least likely to have changed over a 5-year period. Over half the sample
      reported not being involved in any quality assurance activities in the previous 5
      years. Those respondents who were younger, had a postgraduate qualification and
      earned more than 20% of their income from private practice reported higher levels
      of change. CONCLUSIONS: General dental practitioners' work patterns are dynamic
      and appear to be responding to changing needs and demands on their service. The
      main changes were in the types of clinical procedures being carried out. The low
      prevalence of changes reported in auditing and peer review activities needs to be
      investigated further.

PMID- 15475903
TI  - Relative efficacy of oral analgesics after third molar extraction.
AB  - OBJECTIVES: To compare the relative efficacy of analgesics after third molar
      extraction from systematic reviews of randomised, double blind studies. DATA
      SOURCES: Dental trials from systematic reviews of randomised, double-blind
      studies of analgesics in acute pain. DATA SELECTION: Number of patients with
      moderate or severe pain achieving at least half pain relief over 4 to 6 hours
      after a single oral dose of analgesic. DATA EXTRACTION: Independently by two
      reviewers. DATA SYNTHESIS: Use of dichotomous information from active and placebo
      treatments, first to calculate the statistical significance using relative risk,
      and then to evaluate the clinical relevance using number needed to treat (NNT).
      Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase-2 (COX-2)
      inhibitors had the lowest (best) NNTs for the outcome of at least half pain
      relief over 4-6 hours compared with placebo. With the best performing analgesics,
      50-70 patients out of 100 had good pain relief compared with about 10 out of 100
      with placebo. Only paracetamol 600/650 mg plus codeine 60 mg was associated with
      any significant increase in any patient experiencing an adverse event.
      CONCLUSIONS: NSAIDs and COX-2 inhibitors have the lowest (best) NNTs. They may
      also have fewer adverse effects after third molar surgery, though conclusive
      evidence is lacking. At least 80% of analgesic prescribing by UK dentists is in
      line with the best available evidence on efficacy and safety.

PMID- 15475904
TI  - Epidemiological studies of tooth wear and dental erosion in 14-year-old children
      in North West England. Part 1: The relationship with water fluoridation and
      social deprivation.
AB  - OBJECTIVE: The effect of water fluoridation upon dental erosion/tooth wear in the
      UK has not been investigated. This study aimed to compare the prevalence of tooth
      wear in 14-year-old schoolchildren in non-fluoridated and fluoridated districts
      of North West (NW) England. The influence of deprivation and tooth brushing was
      also investigated. DESIGN: A random sample of 10% of the 14-year-old population
      in NW England was selected and stratified according to fluoridation status as
      determined from water authority postcode listings. METHODS: Tooth wear was scored
      on the labial, incisal and palatal/lingual surfaces of the 12 anterior teeth and
      the occlusal surfaces of the first molars. Enamel wear was scored 0, dentine was
      scored 1 or 2, dependent on whether less than or more than a third of the surface
      had exposed dentine. Secondary dentine or pulpal exposure scored 3. Townsend
      deprivation scores were gained from residential post codes. RESULTS: A total of
      2,351 children were examined, of which 637 (27%) lived in the one fluoridated
      district of South Cheshire and 1,714 (73%) lived in 11 non-fluoridated districts.
      Fifty-three per cent of the children had exposed dentine with significantly more
      males affected than females (p<0.001). In the fluoridated district, significantly
      fewer children had exposed dentine on labial and palatal smooth surfaces
      (p<0.001) but no differences were found for incisal and occlusal surfaces. The
      interaction of fluoridation and tooth brushing twice per day resulted in a
      significant (30%) reduction in erosion. Smooth surface wear was more prevalent in
      children resident in affluent areas. CONCLUSION: Children in non-fluoridated
      districts are 1.5 times more likely to have smooth surface wear compared with
      children in fluoridated districts. Fluoridation and use of fluoridated toothpaste
      twice a day provide added protection from dental erosion. The risk of tooth wear
      is greater with increasing affluence.

PMID- 15475905
TI  - Dental treatment in Medieval England.
AB  - Medieval (12th-14th century) medical literature suggests that care of the teeth
      was largely limited to non-invasive treatment. Cures, mainly for toothache and
      "tooth worm" were based on herbal remedies, charms and amulets. Bloodletting was
      advised for certain types of toothache. There is also documentary evidence for
      powders to clean teeth and attempts at filling carious cavities. Surgical
      intervention for oral cancer and facial fracture is also known. Post-operative
      infection and abscess formation can be identified and early forms of false teeth
      are mentioned.

PMID- 15475927
TI  - Preoperative prediction of Gleason grade in radical prostatectomy specimens: the
      influence of different Gleason grades from multiple positive biopsy sites.
AB  - The Gleason score of prostate adenocarcinomas is an important preoperative
      predictor of cancer behavior, and is used to help guide treatment. In the setting
      of more than two positive biopsy sites, pathologists usually grade the tumor at
      each site separately, and the Gleason score may differ from each positive site.
      This study seeks to determine if the highest Gleason score in all biopsy sites,
      or the Gleason score in the site with the highest tumor volume on the needle
      biopsy is the best predictor of final Gleason score in the radical prostatectomy
      specimens. Various preoperative biopsy findings were analyzed. All 151 patients
      had at least two positive biopsy sites and underwent radical prostatectomy.
      Primary and secondary Gleason pattern grades were assigned for each positive
      biopsy site. The tumor volume in the needle biopsy site was defined by the
      percentage of areas of biopsy cores involved by cancer. The radical prostatectomy
      specimens were completely embedded and processed in the whole-mount method. The
      Gleason score from both the biopsy site with the highest Gleason score and the
      biopsy site with the highest tumor volume on the needle biopsy correlated equally
      well with final Gleason score at radical prostatectomy (Spearman correlation
      coefficient =0.54 for both, P<0.001). The Gleason score from both the biopsy site
      with the highest Gleason score and the biopsy site with the highest tumor volume
      on the needle biopsy also correlated with primary Gleason pattern grade at
      radical prostatectomy (Spearman correlation coefficient =0.53 for both, P<0.001).
      Secondary Gleason pattern grade from the biopsy site with the highest tumor
      volume on the needle biopsy correlated with secondary Gleason pattern grade at
      radical prostatectomy slightly better than those from the biopsy site with the
      highest Gleason score (Spearman correlation coefficient, 0.32 vs 0.24; both
      P<0.001). Our data indicate that the highest Gleason score from all sites and the
      Gleason score from the site with the highest tumor volume on the needle biopsy
      are equally and significantly predictive of final Gleason score on radical
      prostatectomy. Both methods of prediction are significantly predictive of primary
      and secondary Gleason pattern grade on radical prostatectomy. We recommend that
      the highest Gleason score from all positive biopsy sites should be used when
      assigning an initial score using needle biopsies.

PMID- 15475929
TI  - Ezrin in primary cutaneous melanoma.
AB  - Ezrin is a member of the ezrin-radixin-moesin family of proteins that link the
      actin-containing cytoskeleton to the plasma membrane. Ezrin is also connected to
      signaling molecules involved in the regulation of cell survival, proliferation
      and migration. Here, we examined the expression of ezrin in 95 primary cutaneous
      melanomas and correlated ezrin expression with conventional prognostic factors
      and biomarkers. From 12 patients metastatic tissue samples were also examined. In
      addition to ezrin staining, Mib-1 proliferation antigen, p53 and Bcl-2 were
      evaluated. Ezrin immunoreactivity was seen in most tumors; only 19 (20%)
      melanomas were negative. A total of 48 (51%) tumors had weak immunoreactivity and
      28 (29%) strong immunoreactivity. The intensity of ezrin immunoreactivity was
      associated with tumor thickness (Breslow, P=0.0008) and with tumor invasion level
      (Clark, P=0.004), thicker tumors having stronger immunoreactivity. Also, there
      was a correlation between higher Mib-1 index in tumors and strong ezrin
      expression. All metastatic samples (n=12) showed positive ezrin immunoreactivity.
      In univariate analysis of survival, patients (n=76) with positive ezrin
      immunoreactivity had worse clinical disease behavior than those (n=19) without
      ezrin immunoreactivity, but the difference was not significant (P=0.19). In
      multivariate analysis of survival, the ezrin immunoreactivity was not a
      significant marker. The results indicate that ezrin is expressed in most primary
      melanomas of the skin and in all metastatic tumors. Ezrin expression correlates
      with tumor thickness and level of invasion suggesting an association between
      ezrin expression and tumor progression.

PMID- 15475928
TI  - Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue
      microarray study.
AB  - Tight junction associated proteins are key molecular components governing
      cellular adhesion, polarity and glandular differentiation. Tight junction
      proteins also play critical roles in cellular proliferation and neoplastic
      pathways via their functions as couplers of the extracellular milieu to
      intracellular signaling pathways and the cytoskeleton. Neoplastic cells
      frequently exhibit structural and functional deficiencies in the tight junction.
      The purpose of this study was to determine the pattern of expression and
      prognostic value of four tight junction associated proteins, claudin-1, claudin
      4, occludin and ZO-1 in a cohort of TNM stage II colon cancer using tissue
      microarray technology. In this study, we retrospectively analyzed, resected and
      otherwise untreated paraffin embedded specimens from 129 consecutive patients
      with TNM stage II colonic carcinomas for claudin-1, claudin-4, occludin and ZO-1
      protein expression by immunohistochemistry. Seventy-five, 58, 56 and 44% of the
      tumors exhibited normal to elevated expression levels (+2 and +3
      immunopositivity) of claudin-1, claudin-4, occludin and ZO-1 respectively. Low
      expression levels of claudin-1 and ZO-1 were directly associated with higher
      tumor grade (P=0.05 and 0.03 respectively). Multivariate analysis indicated that
      lymphovascular invasion (P=0.01) and low levels of claudin-1 (P=0.0001)
      expression were independent predictors of recurrence and that reduced claudin-1
      expression (P=0.0001) was associated with poor survival. This study is the first
      to comprehensively examine the expression of several tight junction associated
      proteins in colonic neoplasms and to correlate their expression with disease
      progression. Loss of claudin-1 expression proved to be a strong predictor of
      disease recurrence and poor patient survival in stage II colon cancer.

PMID- 15475930
TI  - Extra copies of chromosome 2 are a recurring aberration in ALK-negative lymphomas
      with anaplastic morphology.
AB  - The purpose of this study was to evaluate fluorescence in situ hybridization
      abnormalities of the 2p23 anaplastic lymphoma kinase (ALK) gene loci in lymphomas
      with anaplastic morphology. We studied 24 anaplastic large cell lymphomas (ALCL)
      classified by World Health Organization criteria [17 primary nodal/systemic (10
      ALK+, 7 ALK-), seven primary cutaneous], and 17 additional non-Hodgkin's
      lymphomas [one ALK+ B-lineage lymphoma, 14 ALK- diffuse large B-cell lymphomas
      (seven anaplastic variants, five nonanaplastic, two secondary CD30+), two
      follicular lymphomas]. ALK- lymphomas with anaplastic morphology showed extra
      nonrearranged anaplastic lymphoma kinase gene loci (P=0.004) due to trisomy 2
      irrespective of the following factors: B or T/null phenotype (P=0.315),
      diagnostic categories of systemic or cutaneous ALCL or the above-mentioned B-cell
      lymphomas (P=0.131), and CD30 positivity by immunohistochemistry (P=1.000).
      Trisomy 2 was absent in all ALK+ lymphomas (P=0.009), which showed rearranged ALK
      gene loci (P<0.001). Whether trisomy 2 is a primary or secondary event that leads
      to ALK- lymphomas cannot be determined from this study. Its presence in secondary
      B-cell lymphomas suggests that trisomy 2 may be a secondary cytogenetic
      aberration in lymphomas in general. Further investigation of this finding is
      necessary to further our understanding of the heterogeneous group of ALK-
      lymphomas.

PMID- 15475931
TI  - Reduced PTEN expression predicts relapse in patients with breast carcinoma
      treated by tamoxifen.
AB  - Tamoxifen treatment substantially improves the 10-year survival of women with
      estrogen-receptor (ER)-alpha-positive tumors. However, approximately one-third of
      all breast cancer patients with ER-alpha-positive tumors progress on antiestrogen
      therapy. The molecular mechanism(s) involved in antiestrogen-resistant phenotype
      of breast carcinoma is not completely understood. The PTEN (phosphatase and
      tensin homolog deleted on chromosome Ten) gene is a novel candidate tumor
      suppressor that plays an important role in cell cycle regulation and apoptosis by
      regulating Protein kinase-B/Akt activity. Previous studies have shown that PTEN
      downregulation in breast cancer is associated with high-grade tumor, distant
      metastases and poorer disease-free survival. Decreased PTEN and/or increased
      protein kinase B/Akt activity in breast cancer cells has recently been associated
      with resistance to tamoxifen-induced apoptosis. In this study, we have evaluated
      PTEN expression by immunohistochemistry in 100 tamoxifen-treated ER-alpha
      positive breast cancer patients. Reduced PTEN protein expression was associated
      with shorter relapse-free survival. When stage I patients were analyzed
      separately, reduced PTEN expression was a strong predictor of both, shorter
      relapse-free survival and shorter disease-specific survival. An association of
      reduced PTEN expression with shorter relapse-free survival and disease-specific
      survival in stage I patients was still observed after stratification by stage,
      axillary lymph node status, tumor size, grade, and expression of ER-alpha,
      progesterone receptor, and Her-2/neu. In summary, our results showed a strong
      association between downregulation of PTEN expression in ER-alpha-positive tumors
      and failure to tamoxifen treatment.

PMID- 15475932
TI  - Potential autocrine function of vascular endothelial growth factor in head and
      neck cancer via vascular endothelial growth factor receptor-2.
AB  - Vascular endothelial growth factor is a peptide with well-defined actions on the
      vasculature and fundamental role in tumor angiogenesis. Its action in vascular
      endothelium is exerted in a paracrine manner. The immunohistochemical expression
      of this protein by cancer cells in head and neck squamous cell carcinoma was
      correlated with increased tumor aggressiveness and poor survival in previous
      studies. In the past years, an increasing amount of studies demonstrated
      potential autocrine action of vascular endothelial growth factor in various
      neoplasms. However, the existence and the impact of such autocrine action in head
      and neck cancer have not been demonstrated yet. In this retrospective study, we
      evaluated the expression of vascular endothelial growth factor and its receptors
      in neoplastic cells, in a cohort of patients with head and neck squamous cell
      carcinoma, and compared this expression with tumor aggressiveness,
      clinicopathologic parameters and outcome. High expression of vascular endothelial
      growth factor was strongly correlated with high expression of vascular
      endothelial growth factor receptor-2 (but not vascular endothelial growth factor
      receptor-1) on the cancer cells (P<0.001). The co-overexpression of both the
      protein and vascular endothelial growth factor receptor-2 was associated with
      higher tumor proliferation rate (P<0.001). The above co-overexpression also
      correlated with worse survival (log rank P<0.05) in patients with oral-larynx
      squamous cell carcinoma. Our results suggest that an autocrine vascular
      endothelial growth factor loop, mediated via vascular endothelial growth factor
      receptor-2, probably exists in head and neck squamous cell carcinoma. These
      observations support the hypothesis that the use of vascular endothelial growth
      factor receptor-2 inhibitors as adjuvant antiangiogenic therapy might have
      beneficial effects for these patients, by disrupting both paracrine (endothelial
      dependent) and autocrine actions of vascular endothelial growth factor.

PMID- 15475933
TI  - Distribution of Y-chromosome-bearing cells in gonadoblastoma and dysgenetic
      testis in 45,X/46,XY infants.
AB  - Gonadoblastoma is an unusual mixed germ cell-sex cord-stromal tumor that has the
      potential for malignant transformation and 30% of all patients with
      gonadoblastoma develop germ cell tumors mainly dysgerminoma/seminoma. An
      additional 10% gives rise to other malignant germ cell neoplasms. This tumor
      affects a subset of patients with intersex disorders. The age at diagnosis is
      variable ranging from birth to the fourth decade, but around 94% of cases are
      diagnosed during the first three decades of life and there are few cases with
      gonadoblastoma diagnosed in infants. In this paper, we present the histological
      and molecular findings of four patients with gonadal dysgenesis who developed
      gonadoblastoma in the first 2 years of life and one case with bilateral
      dysgerminoma diagnosed at 15 years of age. The sex chromosomes of mosaic patients
      do not distribute homogenously in dysgenetic gonads; however, statistical
      analysis of FISH results revealed significant differences between the XY cell
      line in the gonadoblastoma compared with the dysgenetic testis. Our cases
      demonstrate that tumors could be present at a very early age, so the prophylactic
      removal of the gonads is advised.

PMID- 15475934
TI  - Species identification of mycobacteria in paraffin-embedded tissues: frequent
      detection of nontuberculous mycobacteria.
AB  - Diagnosis of infections caused by mycobacteria, especially nontuberculous
      mycobacteria still represents a difficult task both in microbiology and
      pathology. The aim of this study was to determine the frequency of mycobacterial
      DNA detectable by PCR in formalin-fixed paraffin-embedded tissues showing
      suspicious granulomatous lesions. A total of 190 archival specimens were
      analyzed, using a nested PCR protocol, which amplifies a fragment of the
      mycobacterial 65-kDa heat-shock protein gene. Restriction fragment-length
      polymorphisms and sequencing were utilized to further analyze the obtained PCR
      products. Corresponding microbiological culture results were available for 41
      cases. We detected mycobacterial DNA in 119 cases (63%), of which 71 (60%) were
      positive for Mycobacterium tuberculosis complex DNA and 41 (34%) for DNA of
      nontuberculous mycobacteria. Seven cases (6%) could not be subtyped for technical
      reasons. The largest group of nontuberculous mycobacteria comprised 29 cases (25%
      of the 119 positive cases), which were assigned to Mycobacterium fortuitum
      complex. Mycobacterium avium-intracellulare complex was detected in eight (7%)
      cases, Mycobacterium gordonae in three (2.5%) and Mycobacterium rhodesiae in a
      single case (0.8%). All cases of Mycobacterium tuberculosis were unequivocally
      identified by restriction fragment-length polymorphism analysis. In contrast,
      sequencing provided a gain of information over restriction fragment-length
      polymorphism analysis in 37% of the nontuberculous mycobacteria cases (15 of 41).
      Alignment studies on DNA of nontuberculous mycobacteria showed frequent sequence
      variations, supporting the existence of sequevars. Comparison of molecular data
      to available results of microbiological culture assays showed a good concordance
      of 83%. In conclusion, amplification and sequencing of the mycobacterial 65-kDa
      heat-shock protein gene is an excellent tool for species identification of
      mycobacteria, especially nontuberculous mycobacteria, in formalin-fixed paraffin
      embedded tissues.

PMID- 15475935
TI  - Role of COX-2, thromboxane A2 synthase, and prostaglandin I2 synthase in
      papillary thyroid carcinoma growth.
AB  - The development of papillary thyroid carcinoma is influenced by many factors
      including genetic alterations, growth factors, and physical agents such as
      radiation. Arachidonic acid and its derivatives including prostaglandins (PG) and
      thromboxane along with the enzymes involved in their synthesis have been shown to
      influence the growth of various tumors. We analyzed the immunoreactivity for
      cyclooxygenase-2 (COX-2) and mRNA expression levels of the enzymes COX-2,
      thromboxane A(2) (TXA(2)) synthase, and PGI(2) synthase by RT-PCR in papillary
      carcinomas and matching normal tissues to determine the role of these enzymes in
      the development of papillary thyroid carcinomas. A papillary thyroid carcinoma
      cell line TPC-1 was also studied in vitro to determine the role of the specific
      COX-2 inhibitor NS-398 on COX-2 and vascular endothelial growth factor-A, since
      COX-2 also has a role in regulating tumor angiogenesis. RT-PCR analysis showed
      significant increases in TXA(2) synthase mRNA levels in papillary thyroid
      carcinomas compared to normal thyroid tissues. Although COX-2 mRNA levels were
      generally increased in papillary carcinomas, the differences were not
      statistically significant. There were no significant differences in PGI(2)
      synthase mRNA levels. COX-2 protein expression was greater in papillary carcinoma
      compared to normal thyroid tissues; however, the levels were quite variable. In
      vitro studies with a COX-2 inhibitor, NS-398, showed inhibition of tumor growth
      along with increased levels of COX-2 and vascular endothelial growth factor-A
      mRNA expression. These results indicate that specific enzyme levels in the PG
      synthesis pathway such as TXA(2) synthase are increased in papillary thyroid
      carcinomas. COX-2 also has a role in papillary thyroid growth, since a specific
      inhibitor of COX-2 regulates papillary thyroid carcinoma cell proliferation.
      These results implicate several enzymes in the synthesis of prostanoids as
      regulators of thyroid papillary carcinoma proliferation and suggest that
      increased levels of expression of these enzymes may play a role in the
      pathogenesis of these tumors.

PMID- 15475936
TI  - Cytoplasmic phospholipase A2 alpha overexpression in stromal cells is correlated
      with angiogenesis in human colorectal cancer.
AB  - In colorectal cancer, cyclooxygenase-2 (COX-2) overexpression in stromal cells
      induces angiogenesis through EP2 prostaglandin E2 receptor signaling. Cytoplasmic
      phospholipase A2 (PLA2) alpha preferentially hydrolyses arachidonic acid, which
      is the limiting substrate for prostaglandin production, from membrane
      phospholipids. We therefore investigated a possible relationship between
      cytoplasmic PLA2 and COX-2 overexpression in stromal cells, angiogenesis and
      microsatellite instability in 48 human colorectal adenocarcinomas. Cytoplasmic
      PLA2 and COX-2 expression in stromal cells and vascular endothelial growth factor
      (VEGF) expression in tumor cells were evaluated by immunohistochemistry.
      Microvessel density was assessed in 10 x 400 fields after CD31 staining.
      Microsatellite instability was evaluated by PCR and immunohistochemistry. A total
      of 16 tumors had microsatellite instability. We found an overexpression of
      cytoplasmic PLA2 in superficial stromal cells. These cells corresponded to
      fibroblasts and myofibroblasts. There was an association between the number of
      cytoplasmic PLA2 and COX-2-expressing cells (P=0.006). Cytoplasmic PLA2-positive
      stromal cells usually also expressed COX-2. A high number of cytoplasmic PLA2
      positive stromal cells was correlated with a high microvessel density (P=0.002),
      a strong VEGF (P=0.01) and the absence of microsatellite instability (P=0.001).
      The coordinate overexpression of cytoplasmic PLA2 and COX-2 in stromal cells
      could lead to an important prostaglandin production. These results suggest that
      cytoplasmic PLA2 overexpression in these cells regulates COX-induced angiogenesis
      probably by providing arachidonic acid, which is the limiting factor for
      prostaglandin production. The lower number of cytoplasmic PLA2-positive stromal
      cells in carcinomas with microsatellite instability could be related to their
      lower microvessel density and VEGF expression.

PMID- 15475937
TI  - Positive association of heparanase expression with tumor invasion and lymphatic
      metastasis in gastric carcinoma.
AB  - Tumor invasion and metastasis are the most common causes of death in gastric
      carcinoma. Human heparanase influences tumor invasiveness and angiogenesis.
      Analysis of its expression in gastric carcinoma has been hindered by our
      inability to procure pure cancer cells from heterogeneous tissue. In the present
      study, we analyzed heparanase expression in human primary and metastatic gastric
      carcinoma cells as well as in paired normal gastric epithelial cells by laser
      capture microdissection coupled with reverse transcription-polymerase chain
      reaction (RT-PCR). Tumor tissues, metastatic lymph nodes, and apparently
      uninvolved normal gastric tissues were collected from 30 patients who had
      undergone gastrectomy with radical lymph node dissection for gastric carcinoma
      without preoperative treatment. Bulk tissues and laser capture microdissected
      cell groups were separately subjected to RT-PCR analysis with heparanase-specific
      primers. For bulk tissues, heparanase-specific transcripts were detectable in all
      primary tumor tissues, metastatic lymph nodes, and almost all matching normal
      tissues. RT-PCR analysis after laser capture microdissection showed no detectable
      heparanase expression in matching normal epithelial cell groups. Of the laser
      capture microdissected primary gastric carcinoma cells, 47% (14/30) were
      heparanase positive. Expression was closely associated with greater tumor
      invasiveness, including Borrmann gross type and depth of wall infiltration. For
      metastatic cell groups dissected from lymph nodes, 95% showed clear heparanase
      expression. Furthermore, the extent of lymphatic spread was directly correlated
      to heparanase expression at the primary site. In conclusion, laser capture
      microdissection coupled with RT-PCR is a reliable approach for molecular analysis
      of heparanase expression in gastric carcinoma. Heparanase may facilitate invasion
      and metastasis of gastric carcinoma cells.

PMID- 15475938
TI  - Impact of the 1998 World Health Organization/International Society of Urological
      Pathology classification system for urothelial neoplasms of the kidney.
AB  - The classification of urothelial neoplasms of the kidney traditionally has been
      similar to that of urinary bladder tumors. Several years ago, the classification
      of papillary urothelial neoplasms was revised. The current study focuses on the
      application of the 1998 World Health Organization (WHO)/International Society of
      Urological Pathology classification system to 102 renal pelvic urothelial
      neoplasms and compares it to the 1973 WHO classification scheme. In this study,
      all tumors were classified as urothelial carcinomas, and the majority (85%) were
      papillary. Most patients with papillary tumors presented with 'superficial'
      disease (< or = pT1). With the 1998 system, most papillary carcinomas were high
      grade, and were more often invasive as compared to low-grade tumors. Only 34%
      were low-grade papillary tumors and, of these, most (93%) were noninvasive. With
      the 1973 system, most papillary tumors were grade 2 or 3, with invasion more
      common in grade 3 tumors. By 1973 criteria, grade 2 tumors were a heterogeneous
      group; with 1998 criteria, nearly one-half were high grade and the other half low
      grade. The grade of papillary urothelial carcinomas with both the 1973 and 1998
      grading methods was associated with stage (P=0.001). Our study reveals that
      papillomas and papillary urothelial neoplasms of low malignant potential are
      uncommon tumors in the kidney. Renal pelvic papillary urothelial neoplasms are
      most often carcinomas and are more commonly high grade than low grade. Although
      both the 1973 and 1998 systems showed a significant association with tumor stage,
      grade 2 papillary carcinomas are a heterogeneous group by 1973 criteria. The 1998
      system provides useful information in that it more clearly defines a papillary
      tumor's grade and selects for a group of tumors, namely low-grade papillary
      urothelial carcinomas, for which a low likelihood of invasion can be predicted.

PMID- 15475939
TI  - Chemotherapy for prostate cancer: small steps or leaps and bounds? No huzzahs
      just yet!

PMID- 15475940
TI  - Identification of two contiguous minimally deleted regions on chromosome 1p36.31
      p36.32 in oligodendroglial tumours.
AB  - Loss of the short arm of chromosome 1 is a hallmark of oligodendroglial tumours
      (OTs). Deletion mapping studies in OTs have revealed multiple commonly deleted
      regions on chromosome 1p, suggesting that there are more than one tumour
      suppressor gene. To map critical deletion regions on 1p, a series of 25 OTs were
      examined for loss of heterozygosity (LOH) on 19 polymorphic markers across the 1p
      arm using microsatellite analysis. Our study revealed that 60% of tumours had LOH
      of all informative markers on 1p and identified one tumour showing LOH at
      telomeric markers only. Since this deletion region lies in one of the critical
      deletion intervals defined previously, we then screened another series of 27 OTs
      specifically at 1p36.3 for LOH using nine polymorphic markers. A total of 12%
      (six out of 52) of tumours were found to carry interstitial deletions. The
      allelic status and the deletion breakpoints in these tumours with interstitial
      deletion were further verified by fluorescent in situ hybridisation. The small
      overlapping intervals facilitated the delineation of two contiguous minimally
      deleted regions of 0.76 Mb, defined by D1S468 and D1S2845, and of 0.41 Mb, bound
      by D1S2893 and D1S1608, on 1p36.31-36.32. Based on current reference human genome
      sequence these deletion regions have been sequenced almost to entirety and
      contain eight annotated genes. TP73, DFFB and SHREW1 are the only known genes
      located in these deletion regions, while the others are uncharacterised novel
      genes. In conclusion, our study has narrowed down the critical tumour suppressor
      loci on 1p36.3, in which two minimally deleted regions are mapped, and markedly
      reduced the number of candidate genes to be screened for their involvement in OT
      development.

PMID- 15475941
TI  - Dosage analysis of cancer predisposition genes by multiplex ligation-dependent
      probe amplification.
AB  - Multiplex ligation-dependent probe amplification (MLPA) is a recently described
      method for detecting gross deletions or duplications of DNA sequences,
      aberrations which are commonly overlooked by standard diagnostic analysis. To
      determine the incidence of copy number variants in cancer predisposition genes
      from families in the Wessex region, we have analysed the hMLH1 and hMSH2 genes in
      patients with hereditary nonpolyposis colorectal cancer (HNPCC), BRCA1 and BRCA2
      in families with hereditary breast/ovarian cancer (BRCA) and APC in patients with
      familial adenomatous polyposis coli (FAP). Hereditary nonpolyposis colorectal
      cancer (n=162) and FAP (n=74) probands were fully screened for small mutations,
      and cases for which no causative abnormality were found (HNPCC, n=122; FAP, n=24)
      were screened by MLPA. Complete or partial gene deletions were identified in
      seven cases for hMSH2 (5.7% of mutation-negative HNPCC; 4.3% of all HNPCC), no
      cases for hMLH1 and six cases for APC (25% of mutation negative FAP; 8% of all
      FAP). For BRCA1 and BRCA2, a partial mutation screen was performed and 136
      mutation-negative cases were selected for MLPA. Five deletions and one
      duplication were found for BRCA1 (4.4% of mutation-negative BRCA cases) and one
      deletion for BRCA2 (0.7% of mutation-negative BRCA cases). Cost analysis
      indicates it is marginally more cost effective to perform MLPA prior to point
      mutation screening, but the main advantage gained by prescreening is a greatly
      reduced reporting time for the patients who are positive. These data demonstrate
      that dosage analysis is an essential component of genetic screening for cancer
      predisposition genes.

PMID- 15475944
TI  - Sexual life in Pharaonic Egypt: towards a urological view.
AB  - Sex is a basic human need, common to all people at all times. It is evident that
      the ancient Egyptians were real human beings, not only a people who built massive
      pyramids and made mummies of their dead. The ancient Egyptians had a rich and
      varied sexual life, which they found an opportunity to describe in words and
      pictures. As in the other early primitive civilizations, erotic matters were of
      prime importance and became an integral part of life. In Pharaonic times, the
      Egyptians described impotence and recorded several methods to increase the sexual
      power. In the present paper, we will shed light on some aspects of the sexual
      life in ancient Egypt that may be interesting to the urologists, including
      ancient Egyptian concepts of sex and erotic matters, their own way of treatment
      of impotence and Min, the Egyptian fertility God.

PMID- 15475945
TI  - Analysis of retrograde ejaculation using color Doppler ultrasonography before and
      after transurethral collagen injection.
AB  - Transurethral bladder neck collagen injection therapy was performed in a patient
      with retrograde ejaculation. The phenomenon of retrograde ejaculation and its
      correction after the therapy were clearly demonstrated by color Doppler
      ultrasonography. To our knowledge this is the first report showing successful
      observation of retrograde ejaculation using color Doppler ultrasonography.

PMID- 15475946
TI  - Synaptobrevin is essential for fast synaptic-vesicle endocytosis.
AB  - Synaptobrevin-2 (VAMP-2), the major SNARE protein of synaptic vesicles, is
      required for fast calcium-triggered synaptic-vesicle exocytosis. Here we show
      that synaptobrevin-2 is also essential for fast synaptic-vesicle endocytosis. We
      demonstrate that after depletion of the readily releasable vesicle pool,
      replenishment of the pool is delayed by knockout of synaptobrevin. This delay was
      not from a loss of vesicles, because the total number of pre-synaptic vesicles,
      docked vesicles and actively recycling vesicles was unaffected. However, altered
      shape and size of the vesicles in synaptobrevin-deficient synapses suggests a
      defect in endocytosis. Consistent with such a defect, the stimulus-dependent
      endocytosis of horseradish peroxidase and fluorescent FM1-43 were delayed,
      indicating that fast vesicle endocytosis may normally be nucleated by a SNARE
      dependent coat. Thus, synaptobrevin is essential for two fast synapse-specific
      membrane trafficking reactions: fast exocytosis for neurotransmitter release and
      fast endocytosis that mediates rapid reuse of synaptic vesicles.

PMID- 15475947
TI  - Adaptive divergence in pigment composition promotes phytoplankton biodiversity.
AB  - The dazzling diversity of the phytoplankton has puzzled biologists for decades.
      The puzzle has been enlarged rather than solved by the progressive discovery of
      new phototrophic microorganisms in the oceans, including picocyanobacteria, pico
      eukaryotes, and bacteriochlorophyll-based and rhodopsin-based phototrophic
      bacteria. Physiological and genomic studies suggest that natural selection
      promotes niche differentiation among these phototrophic microorganisms,
      particularly with respect to their photosynthetic characteristics. We have
      analysed competition for light between two closely related picocyanobacteria of
      the Synechococcus group that we isolated from the Baltic Sea. One of these two
      has a red colour because it contains the pigment phycoerythrin, whereas the other
      is blue-green because it contains high contents of the pigment phycocyanin. Here
      we report theory and competition experiments that reveal stable coexistence of
      the two picocyanobacteria, owing to partitioning of the light spectrum. Further
      competition experiments with a third marine cyanobacterium, capable of adapting
      its pigment composition, show that this species persists by investing in the
      pigment that absorbs the colour not used by its competitors. These results
      demonstrate the adaptive significance of divergence in pigment composition of
      phototrophic microorganisms, which allows an efficient utilization of light
      energy and favours species coexistence.

PMID- 15475948
TI  - MYC inactivation uncovers pluripotent differentiation and tumour dormancy in
      hepatocellular cancer.
AB  - Hepatocellular carcinoma is generally refractory to clinical treatment. Here, we
      report that inactivation of the MYC oncogene is sufficient to induce sustained
      regression of invasive liver cancers. MYC inactivation resulted en masse in
      tumour cells differentiating into hepatocytes and biliary cells forming bile duct
      structures, and this was associated with rapid loss of expression of the tumour
      marker alpha-fetoprotein, the increase in expression of liver cell markers
      cytokeratin 8 and carcinoembryonic antigen, and in some cells the liver stem cell
      marker cytokeratin 19. Using in vivo bioluminescence imaging we found that many
      of these tumour cells remained dormant as long as MYC remain inactivated;
      however, MYC reactivation immediately restored their neoplastic features. Using
      array comparative genomic hybridization we confirmed that these dormant liver
      cells and the restored tumour retained the identical molecular signature and
      hence were clonally derived from the tumour cells. Our results show how oncogene
      inactivation may reverse tumorigenesis in the most clinically difficult cancers.
      Oncogene inactivation uncovers the pluripotent capacity of tumours to
      differentiate into normal cellular lineages and tissue structures, while
      retaining their latent potential to become cancerous, and hence existing in a
      state of tumour dormancy.

PMID- 15475949
TI  - Behavioral equivalence, but not neural equivalence--neural evidence of
      alternative strategies in mathematical thinking.
AB  - In a functional magnetic resonance imaging study, we investigated how people
      solve mathematically equivalent problems presented in two alternative formats:
      verbal, story format or symbolic, equation format. Although representation format
      had no effect on behavior, anterior prefrontal activation was greater in the
      story condition and posterior parietal activation was greater in the equation
      condition. These results show that there exist alternative neural pathways that
      implement different and yet equally efficient problem-solving strategies.

PMID- 15475950
TI  - Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage
      of neuronal branches.
AB  - Amyloid plaques are a hallmark of Alzheimer disease, but their importance in its
      pathogenesis is controversial. By neuronal labeling and transcranial two-photon
      imaging, we show in a transgenic mouse model of Alzheimer disease that dendrites
      passing through or near fibrillar amyloid deposits undergo spine loss and shaft
      atrophy, and nearby axons develop large varicosities, together leading to neurite
      breakage and large-scale, permanent disruption of neuronal connections. Thus,
      fibrillar amyloid deposition is more detrimental to neuronal circuitry than
      previously thought, underscoring the importance of prevention and early clearance
      of plaques.

PMID- 15475951
TI  - Subcellular domain-restricted GABAergic innervation in primary visual cortex in
      the absence of sensory and thalamic inputs.
AB  - Distinct classes of GABAergic synapses target restricted subcellular domains,
      thereby differentially regulating the input, integration and output of principal
      neurons, but the underlying mechanism for such synapse segregation is unclear.
      Here we show that the distributions of two major classes of GABAergic synapses
      along the perisomatic and dendritic domains of pyramidal neurons were
      indistinguishable between primary visual cortex in vivo and cortical organotypic
      cultures. Therefore, subcellular synapse targeting is independent of thalamic
      input and probably involves molecular labels and experience-independent forms of
      activity.

PMID- 15475952
TI  - Unraveling multisensory integration: patchy organization within human STS
      multisensory cortex.
AB  - Although early sensory cortex is organized along dimensions encoded by receptor
      organs, little is known about the organization of higher areas in which different
      modalities are integrated. We investigated multisensory integration in human
      superior temporal sulcus using recent advances in parallel imaging to perform
      functional magnetic resonance imaging (fMRI) at very high resolution. These
      studies suggest a functional architecture in which information from different
      modalities is brought into close proximity via a patchy distribution of inputs,
      followed by integration in the intervening cortex.

PMID- 15475953
TI  - Par6alpha signaling controls glial-guided neuronal migration.
AB  - Neuronal migrations along glial fibers provide a primary pathway for the
      formation of cortical laminae. To examine the mechanisms underlying glial-guided
      migration, we analyzed the dynamics of cytoskeletal and signaling components in
      living neurons. Migration involves the coordinated two-stroke movement of a
      perinuclear tubulin 'cage' and the centrosome, with the centrosome moving forward
      before nuclear translocation. Overexpression of mPar6alpha disrupts the
      perinuclear tubulin cage, retargets PKCzeta and gamma-tubulin away from the
      centrosome, and inhibits centrosomal motion and neuronal migration. Thus, we
      propose that during neuronal migration the centrosome acts to coordinate
      cytoskeletal dynamics in response to mPar6alpha-mediated signaling.

PMID- 15475954
TI  - RITS acts in cis to promote RNA interference-mediated transcriptional and post
      transcriptional silencing.
AB  - RNA interference is a conserved mechanism by which double-stranded RNA is
      processed into short interfering RNAs (siRNAs) that can trigger both post
      transcriptional and transcriptional gene silencing. In fission yeast, the RNA
      induced initiation of transcriptional gene silencing (RITS) complex contains
      Dicer-generated siRNAs and is required for heterochromatic silencing. Here we
      show that RITS components, including Argonaute protein, bind to all known
      heterochromatic loci. At the mating-type region, RITS is recruited to the
      centromere-homologous repeat cenH in a Dicer-dependent manner, whereas the
      spreading of RITS across the entire 20-kb silenced domain, as well as its
      subsequent maintenance, requires heterochromatin machinery including Swi6 and
      occurs even in the absence of Dicer. Furthermore, our analyses suggest that RNA
      interference machinery operates in cis as a stable component of heterochromatic
      domains with RITS tethered to silenced loci by methylation of histone H3 at Lys9.
      This tethering promotes the processing of transcripts and generation of
      additional siRNAs for heterochromatin maintenance.

PMID- 15475955
TI  - Constitutional aneuploidy and cancer predisposition caused by biallelic mutations
      in BUB1B.
AB  - Mosaic variegated aneuploidy is a rare recessive condition characterized by
      growth retardation, microcephaly, childhood cancer and constitutional mosaicism
      for chromosomal gains and losses. In five families with mosaic variegated
      aneuploidy, including two with embryonal rhabdomyosarcoma, we identified
      truncating and missense mutations of BUB1B, which encodes BUBR1, a key protein in
      the mitotic spindle checkpoint. These data are the first to relate germline
      mutations in a spindle checkpoint gene with a human disorder and strongly support
      a causal link between aneuploidy and cancer development.

PMID- 15475956
TI  - Cited2 controls left-right patterning and heart development through a Nodal
      Pitx2c pathway.
AB  - Malformations of the septum, outflow tract and aortic arch are the most common
      congenital cardiovascular defects and occur in mice lacking Cited2, a
      transcriptional coactivator of TFAP2. Here we show that Cited2(-/-) mice also
      develop laterality defects, including right isomerism, abnormal cardiac looping
      and hyposplenia, which are suppressed on a mixed genetic background. Cited2(-/-)
      mice lack expression of the Nodal target genes Pitx2c, Nodal and Ebaf in the left
      lateral plate mesoderm, where they are required for establishing laterality and
      cardiovascular development. CITED2 and TFAP2 were detected at the Pitx2c promoter
      in embryonic hearts, and they activate Pitx2c transcription in transient
      transfection assays. We propose that an abnormal Nodal-Pitx2c pathway represents
      a unifying mechanism for the cardiovascular malformations observed in Cited2(-/-)
      mice, and that such malformations may be the sole manifestation of a laterality
      defect.

PMID- 15475957
TI  - Splenic stroma drives mature dendritic cells to differentiate into regulatory
      dendritic cells.
AB  - The fates of dendritic cells (DCs) after antigen presentation have been studied
      extensively, but the influence of lymphoid microenvironments on DCs is mostly
      unknown. Here, using splenic stromal cells to mimic the immune microenvironment,
      we show that contact with stromal cells promoted mature DCs to proliferate in a
      fibronectin-dependent way and that both stromal cell contact and stromal cell
      derived transforming growth factor-beta induced their differentiation into a new
      regulatory DC subset. We have identified an in vivo counterpart in the spleen
      with similar phenotype and functions. These differentiated DCs secreted nitric
      oxide, which mediated the suppression of T cell proliferation in response to
      antigen presentation by mature DCs. Thus, our findings identify an important
      mechanism by which the microenvironment regulates immune responses.

PMID- 15475958
TI  - Cognate CD4(+) T cell licensing of dendritic cells in CD8(+) T cell immunity.
AB  - Several studies have indicated that CD8(+) T cells require CD4(+) T cell help for
      memory formation. Evidence suggests that such help can be antigen independent,
      challenging whether the 'licensing' of dendritic cells (DCs) by CD4(+) T cells is
      ever required for cytotoxic T lymphocyte (CTL) responses. We show here that help
      is essential for the generation of CTL immunity to herpes simplex virus 1 and
      that CD4(+) T cells mediate help in a cognate, antigen-specific way. We provide
      direct in vivo evidence for DC licensing by helper T cells and show that
      licensing is rapid and essential for the formation of effector and memory CTLs.
      In situations in which DCs are poorly licensed by pathogen-derived signals, our
      findings suggest that CTL immunity may be heavily dependent on cognate DC
      licensing.

PMID- 15475959
TI  - Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2
      responses.
AB  - Expression of the transcription factor GATA-3 is strongly associated with T
      helper type 2 (T(H)2) differentiation, but genetic evidence for its involvement
      in this process has been lacking. Here, we generated a conditional GATA-3
      deficient mouse line. In vitro deletion of Gata3 diminished both interleukin 4
      (IL-4)-dependent and IL-4-independent T(H)2 cell differentiation; without GATA-3,
      T(H)1 differentiation occurred in the absence of IL-12 and interferon-gamma.
      Gata3 deletion limited the growth of T(H)2 cells but not T(H)1 cells. Deletion of
      Gata3 from established T(H)2 cells abolished IL-5 and IL-13 but not IL-4
      production. In vivo deletion of Gata3 using OX40-Cre eliminated T(H)2 responses
      and allowed the development of interferon-gamma-producing cells in mice infected
      with Nippostrongylus brasiliensis. Thus, GATA-3 serves as a principal switch in
      determining T(H)1-T(H)2 responses.

PMID- 15475960
TI  - Strong nonlinear current-voltage behaviour in perovskite-derivative calcium
      copper titanate.
AB  - The discovery of a giant dielectric constant of 10(5) in CaCu(3)Ti(4)O(12) has
      increased interest in this perovskite-type oxide. Here we demonstrate that, in
      addition to high permittivity, CaCu(3)Ti(4)O(12) has remarkably strong nonlinear
      current-voltage characteristics without the addition of any dopants. An intrinsic
      electrostatic barrier at the grain boundaries is responsible for the unusual
      nonlinear behaviour. The nonlinear coefficient of CaCu(3)Ti(4)O(12) reaches a
      value of 900, which is even greater than that of the varistor material ZnO. As a
      result, CaCu(3)Ti(4)O(12) may lead to efficient switching and gas-sensing
      devices.

PMID- 15475961
TI  - Epitaxial growth of InP nanowires on germanium.
AB  - The growth of III-V semiconductors on silicon would allow the integration of
      their superior (opto-)electronic properties with silicon technology. But
      fundamental issues such as lattice and thermal expansion mismatch and the
      formation of antiphase domains have prevented the epitaxial integration of III-V
      with group IV semiconductors. Here we demonstrate the principle of epitaxial
      growth of III-V nanowires on a group IV substrate. We have grown InP nanowires on
      germanium substrates by a vapour-liquid-solid method. Although the crystal
      lattice mismatch is large (3.7%), the as-grown wires are monocrystalline and
      virtually free of dislocations. X-ray diffraction unambiguously demonstrates the
      heteroepitaxial growth of the nanowires. In addition, we show that a low
      resistance electrical contact can be obtained between the wires and the
      substrate.

PMID- 15475962
TI  - Salt-sensitive hypertension is triggered by Ca2+ entry via Na+/Ca2+ exchanger
      type-1 in vascular smooth muscle.
AB  - Excessive salt intake is a major risk factor for hypertension. Here we identify
      the role of Na(+)/Ca(2+) exchanger type 1 (NCX1) in salt-sensitive hypertension
      using SEA0400, a specific inhibitor of Ca(2+) entry through NCX1, and genetically
      engineered mice. SEA0400 lowers arterial blood pressure in salt-dependent
      hypertensive rat models, but not in other types of hypertensive rats or in
      normotensive rats. Infusion of SEA0400 into the femoral artery in salt-dependent
      hypertensive rats increases arterial blood flow, indicating peripheral
      vasodilation. SEA0400 reverses ouabain-induced cytosolic Ca(2+) elevation and
      vasoconstriction in arteries. Furthermore, heterozygous NCX1-deficient mice have
      low salt sensitivity, whereas transgenic mice that specifically express NCX1.3 in
      smooth muscle are hypersensitive to salt. SEA0400 lowers the blood pressure in
      salt-dependent hypertensive mice expressing NCX1.3, but not in SEA0400
      insensitive NCX1.3 mutants. These findings indicate that salt-sensitive
      hypertension is triggered by Ca(2+) entry through NCX1 in arterial smooth muscle
      and suggest that NCX1 inhibitors might be useful therapeutically.

PMID- 15475963
TI  - Cardiomyocyte-restricted peroxisome proliferator-activated receptor-delta
      deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy.
AB  - Fatty acid oxidation (FAO) is a primary energy source for meeting the heart's
      energy requirements. Peroxisome proliferator-activated receptor-delta (PPAR
      delta) may have important roles in FAO. But it remains unclear whether PPAR-delta
      is required for maintaining basal myocardial FAO. We show that cre-loxP-mediated
      cardiomyocyte-restricted deletion of PPAR-delta in mice downregulates
      constitutive expression of key FAO genes and decreases basal myocardial FAO.
      These mice have cardiac dysfunction, progressive myocardial lipid accumulation,
      cardiac hypertrophy and congestive heart failure with reduced survival. Thus,
      chronic myocardial PPAR-delta deficiency leads to lipotoxic cardiomyopathy.
      Together, our data show that PPAR-delta is a crucial determinant of constitutive
      myocardial FAO and is necessary to maintain energy balance and normal cardiac
      function. We suggest that PPAR-delta is a potential therapeutic target in
      treating lipotoxic cardiomyopathy and other heart diseases.

PMID- 15475964
TI  - Centromeric chromatin exhibits a histone modification pattern that is distinct
      from both euchromatin and heterochromatin.
AB  - Post-translational histone modifications regulate epigenetic switching between
      different chromatin states. Distinct histone modifications, such as acetylation,
      methylation and phosphorylation, define different functional chromatin domains,
      and often do so in a combinatorial fashion. The centromere is a unique
      chromosomal locus that mediates multiple segregation functions, including
      kinetochore formation, spindle-mediated movements, sister cohesion and a mitotic
      checkpoint. Centromeric (CEN) chromatin is embedded in heterochromatin and
      contains blocks of histone H3 nucleosomes interspersed with blocks of CENP-A
      nucleosomes, the histone H3 variant that provides a structural and functional
      foundation for the kinetochore. Here, we demonstrate that the spectrum of histone
      modifications present in human and Drosophila melanogaster CEN chromatin is
      distinct from that of both euchromatin and flanking heterochromatin. We speculate
      that this distinct modification pattern contributes to the unique domain
      organization and three-dimensional structure of centromeric regions, and/or to
      the epigenetic information that determines centromere identity.

PMID- 15475965
TI  - A mutant chaperonin with rearranged inter-ring electrostatic contacts and
      temperature-sensitive dissociation.
AB  - The chaperonin GroEL assists protein folding through ATP-dependent, cooperative
      movements that alternately create folding chambers in its two rings. The
      substitution E461K at the interface between these two rings causes temperature
      sensitive, defective protein folding in Escherichia coli. To understand the
      molecular defect, we have examined the mutant chaperonin by cryo-EM. The normal
      out-of-register alignment of contacts between subunits of opposing wild-type
      rings is changed in E461K to an in-register one. This is associated with loss of
      cooperativity in ATP binding and hydrolysis. Consistent with the loss of negative
      cooperativity between rings, the cochaperonin GroES binds simultaneously to both
      E461K rings. These GroES-bound structures were unstable at higher temperature,
      dissociating into complexes of single E461K rings associated with GroES. Lacking
      the allosteric signal from the opposite ring, these complexes cannot release
      their GroES and become trapped, dead-end states.

PMID- 15475966
TI  - Observation of internal cleavage and ligation reactions of a ribozyme.
AB  - We have used single-molecule spectroscopy to untangle conformational dynamics and
      internal chemistry in the hairpin ribozyme. The active site of the ribozyme is
      stably formed by docking two internal loops, but upon cleavage undocking is
      accelerated by two orders of magnitude. The markedly different kinetic properties
      allow us to differentiate cleaved and ligated forms, and thereby observe multiple
      cycles of internal cleavage and ligation of a ribozyme in a uniquely direct way.
      The position of the internal equilibrium is biased toward ligation, but the
      cleaved ribozyme undergoes several undocking events before ligation, during which
      products may dissociate. Formation of the stably docked active site, rapid
      undocking after cleavage, and a strong bias toward ligation should combine to
      generate a stable circular template for the synthesis of the viral (+) strand and
      thus ensure a productive replication cycle.

PMID- 15475967
TI  - Substrate-assisted catalysis of peptide bond formation by the ribosome.
AB  - The ribosome accelerates the rate of peptide bond formation by at least 10(7)
      fold, but the catalytic mechanism remains controversial. Here we report evidence
      that a functional group on one of the tRNA substrates plays an essential
      catalytic role in the reaction. Substitution of the P-site tRNA A76 2' OH with 2'
      H or 2' F results in at least a 10(6)-fold reduction in the rate of peptide bond
      formation, but does not affect binding of the modified substrates. Such substrate
      assisted catalysis is relatively uncommon among modern protein enzymes, but it is
      a property predicted to be essential for the evolution of enzymatic function.
      These results suggest that substrate assistance has been retained as a catalytic
      strategy during the evolution of the prebiotic peptidyl transferase center into
      the modern ribosome.

PMID- 15475968
TI  - Internal recognition through PDZ domain plasticity in the Par-6-Pals1 complex.
AB  - PDZ protein interaction domains are typically selective for C-terminal ligands,
      but non-C-terminal, 'internal' ligands have also been identified. The PDZ domain
      from the cell polarity protein Par-6 binds C-terminal ligands and an internal
      sequence from the protein Pals1/Stardust. The structure of the Pals1-Par-6 PDZ
      complex reveals that the PDZ ligand-binding site is deformed to allow for
      internal binding. Whereas binding of the Rho GTPase Cdc42 to a CRIB domain
      adjacent to the Par-6 PDZ regulates binding of C-terminal ligands, the
      conformational change that occurs upon binding of Pals1 renders its binding
      independent of Cdc42. These results suggest a mechanism by which the requirement
      for a C terminus can be readily bypassed by PDZ ligands and reveal a complex set
      of cooperative and competitive interactions in Par-6 that are likely to be
      important for cell polarity regulation.

PMID- 15475969
TI  - Structural mechanism of allosteric substrate specificity regulation in a
      ribonucleotide reductase.
AB  - Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides into
      deoxyribonucleotides, which constitute the precursor pools used for DNA synthesis
      and repair. Imbalances in these pools increase mutational rates and are
      detrimental to the cell. Balanced precursor pools are maintained primarily
      through the regulation of the RNR substrate specificity. Here, the molecular
      mechanism of the allosteric substrate specificity regulation is revealed through
      the structures of a dimeric coenzyme B12-dependent RNR from Thermotoga maritima,
      both in complexes with four effector-substrate nucleotide pairs and in three
      complexes with only effector. The mechanism is based on the flexibility of loop
      2, a key structural element, which forms a bridge between the specificity
      effector and substrate nucleotides. Substrate specificity is achieved as
      different effectors and their cognate substrates stabilize specific discrete loop
      2 conformations. The mechanism of substrate specificity regulation is probably
      general for most class I and class II RNRs.

PMID- 15475970
TI  - 'All about research'--looking back at the 1987 Cervical Cancer Inquiry.

PMID- 15475971
TI  - Early intervention for psychosis in New Zealand.

PMID- 15475972
TI  - Missed opportunities for better health outcomes in New Zealand.

PMID- 15475973
TI  - Complaints against doctors.

PMID- 15475974
TI  - Familial Mediterranean fever.

PMID- 15475976
TI  - Early diagnosis and treatment in psychotic disorders: an achievable healthcare
      reform strategy.

PMID- 15475975
TI  - Immunisation and the importance of good timing.

PMID- 15475977
TI  - Maternal and demographic factors associated with non-immunisation of Pacific
      infants living in New Zealand.
AB  - AIM: To identify the proportion of infants who had not received their first dose
      of the primary immunisation series at approximately 6 weeks of age, and to
      identify the maternal and demographic factors associated with non-immunisation.
      METHOD: The data were gathered as part of the Pacific Islands Families (PIF):
      First Two Years of Life Study in which 1376 mothers were interviewed about the
      immunisation status of their infant. Mothers responded to questions about whether
      their child had been immunised, who administered the vaccines, and how satisfied
      they were with the care and treatment of their child in that context. RESULTS:
      Twenty-seven percent of the mothers reported that they had not had their infant
      immunised at approximately six-weeks of age. Factors significantly associated
      (p<0.05) with non-immunisation were ethnic group, maternal birth place, parity,
      difficulty with transport, and age of the baby at the time of the interview.
      CONCLUSIONS: These findings demonstrate the need for education about the
      importance of the primary immunisation series and the current schedules, together
      with community resources to support mothers in the context of this infant health
      care initiative. Improving immunisation uptake through education may not be
      sufficient with the more widespread issues of deprivation and social equity
      needing to be addressed.

PMID- 15475978
TI  - Decades of disparity: widening ethnic mortality gaps from 1980 to 1999.
AB  - BACKGROUND: Maori and Pacific deaths were severely undercounted in the mid-1980s
      and first half of 1990s, resulting in numerator-denominator bias when calculating
      mortality rates by ethnicity. We used the New Zealand Census-Mortality Study to
      adjust for this bias and calculate corrected ethnic-specific mortality rates from
      1980 to 1999. METHODS: Age-specific adjusters were calculated for the period 1980
      99. They were applied to mortality data to obtain a corrected number of deaths.
      Mortality rates (by age and gender) were calculated by dividing the total number
      of adjusted deaths by the respective census counts. RESULTS: Contrary to
      unadjusted rates, corrected Maori and Pacific mortality rates were clearly higher
      than non- Maori non-Pacific rates during the 1980s and early 1990s. From 1980-84
      (1361 per 100,000 for males and 965 per 100,000 for females) to 1996-99 (1258 and
      894), there was only a modest decrease in Maori 1 to 74 year old mortality rates.
      Pacific mortality rates changed little from 1980-84 (1264 and 672) to 1996-99
      (1144 and 696 per 100,000 for males and females respectively). Non-Maori non
      Pacific mortality rates, however, decreased by about 30% from 1980-84 (919 and
      553) to 1996-99 (641 and 407 per 100,000 for males and females, respectively).
      Cancer (lung, prostate, breast, colorectal) mortality rates tended to increase
      over time among Maori compared to steadily decreasing among non-Maori non
      Pacific. Of note, Pacific colorectal cancer mortality rates have increased by
      about ten-fold during the 1980s and 1990s. All ethnic groups experienced falls in
      cardiovascular disease mortality rates, but the decreases were much greater among
      non-Maori non-Pacific. CONCLUSION: The gaps between Maori and non-Maori non
      Pacific mortality widened over the 1980s and 1990s mainly due to steadily
      declining non-Maori non-Pacific mortality rates and stagnant Maori mortality
      rates. Likewise, the gaps between Pacific and non-Maori non-Pacific mortality
      also widened during that period.

PMID- 15475979
TI  - Population need and geographical access to general practitioners in rural New
      Zealand.
AB  - AIMS: To use a geographical information system (GIS) approach to demonstrate the
      extent to which different areas in New Zealand vary in their geographical access
      to GPs, and to analyse the extent to which spatial access varies in relation to
      different population groups. METHODS: Three methods; population/GP ratios, least
      cost path analysis (LCPA), and an allocation method (which considered the
      capacity constraint of GPs) were used to demonstrate differences in geographic
      accessibility to GPs. Travel time, and distance to the closest GP, was calculated
      for every census enumeration district in New Zealand (n=38336)--thus enabling
      population-based accessibility statistics to be calculated and aggregated to the
      territorial local authority level. These calculations include the average travel
      time if everybody visited a GP once and the population more than 30 minutes from
      a GP. The composition of this population is analysed according to three criteria
      of need: the level of deprivation (NZDep2001), ethnicity (%Maori), and age (% <5
      years, and %65 years and over). RESULTS: There are significant regional
      variations in geographical accessibility in New Zealand, and these differences
      are dependent upon the method to calculate accessibility. Ratio measures give a
      different picture of GP access than the other two indicators, reflecting the fact
      that TAs with similar ratios often have wide variations in travel times as well
      as the size and proportion of the population living more than 30 minutes from the
      closest GP. TAs with larger numbers and a higher proportion of their populations
      living in such areas tend to be more deprived and have a higher proportion of
      Maori, especially in the North Island. There appears to be no significant trend
      by age. CONCLUSION: Given the health and service consequences of poor access, the
      results suggest that more attention needs to be paid to extending the spatial
      information base in primary care, in order to achieve more effective planning of
      services for disadvantaged populations.

PMID- 15475980
TI  - Maori responsiveness in health and medical research: key issues for researchers
      (part 1).
AB  - INTRODUCTION: Application for contestable government-research funding and ethical
      approval requires researchers to outline how their intended research project
      contributes to Maori development or advancement. METHODS AND RESULTS: When
      formulating their research proposals, the key issues for researchers are research
      utility, defining Maori, informed consent, confidentiality, issues with human
      tissues and genetic material, participant remuneration and recognition (koha),
      intellectual property, and involvement of local Maori health or social services.
      CONCLUSIONS: The most common Maori responsiveness issues in research applications
      can be readily approached by researchers who address straightforward
      methodological concerns, by working through precedents established by peers and
      colleagues, as well as by working with end-users of their research.

PMID- 15475981
TI  - Maori responsiveness in health and medical research: clarifying the roles of the
      researcher and the institution (part 2).
AB  - INTRODUCTION: The combination of the Health Research Council's Guidelines for
      researchers on health research involving Maori and the 1998 revision of the
      National application form for ethical approval generated an expectation that all
      research development required consultation with Maori. METHODS AND RESULTS: This
      paper clarifies issues of consultation for health researchers in two ways.
      Firstly, the historical development of the focus on the Maori research
      responsiveness is outlined. Secondly, we argue that research institutions, rather
      than researchers, need to take a lead role in consulting on research issues with
      Maori organisations. CONCLUSIONS: Consultation with Maori at the institutional
      level could help clarify and address key ethical issues in research--while
      reducing the workload for researchers, Maori organisations, and host institutions
      alike.

PMID- 15475982
TI  - Clinical practice guidelines' development and use in New Zealand: an evolving
      process.
AB  - AIMS: This study explores the use of evidence-based guidelines by New Zealand
      general practitioners, and describes strategies developed to overcome identified
      barriers in the New Zealand setting. METHODS: In-depth, semi-structured
      interviews with a purposeful sample of New Zealand guideline stakeholders
      including policy makers and general practitioners. Data were analysed using
      inductive thematic analysis. Feedback of emergent themes to the New Zealand
      Guidelines Group (NZGG) and further collaboration resulted in strategies to
      overcome barriers to use, some of which have now been implemented. RESULTS: At
      the time of the research (2000/2001), general practitioners reported that they
      did not regularly use guidelines to support decision-making regarding patient
      care. Reasons given included guidelines formats not being recognisable or user
      friendly, lack of general practitioner involvement in prioritisation and
      development processes, influence of stakeholders, and recommendations not being
      accessible or relevant. Policy and other interviewed stakeholders reported
      general acceptance of guidelines, however there were minimal interfaces between
      the NZGG and these organisations. CONCLUSIONS: Effective implementation of
      guidelines requires more than guidelines endorsement by policy stakeholders and
      passive dissemination strategies, but rather an understanding of the issues
      facing general practitioners and their attitudes to guideline use.

PMID- 15475983
TI  - Infectious diseases--far from defeated.

PMID- 15475984
TI  - Meningitis: tragedy, culture, and blame.

PMID- 15475985
TI  - The New Zealand Meningococcal Vaccine Strategy: a tailor-made vaccine to combat a
      devastating epidemic.
AB  - The New Zealand Meningococcal Vaccine Strategy aims to end the devastating 14
      year epidemic of B:4:P1.7b,4 group B meningococcal disease in New Zealand through
      a mass immunisation programme to all under 20 year olds using a tailor-made
      vaccine (MeNZB). This paper describes the scientific rationale, development, and
      key components of the New Zealand Meningococcal Vaccine Strategy. A summary of
      the efficacy and safety data of existing outer membrane vesicle group B
      meningococcal vaccines is included as these data critically support the Strategy.

PMID- 15475986
TI  - Prevention of group B meningococcal disease by vaccination: a difficult task.
AB  - New Zealand has embarked on an immunisation program to reduce the incidence of
      disease caused by serogroup B Neisseria meningitidis. Similar immunisation
      programs in Norway and South America have shown good efficacy in older vaccinees
      (ie, persons receiving vaccinations), but variable efficacy in younger vaccinees.
      Protective efficacy correlates well with the ability of the vaccine to stimulate
      a fourfold rise in serum bactericidal antibodies. Unfortunately, second and third
      doses of serogroup B N. meningitidis vaccines do not boost serum bactericidal
      antibody titres to very high levels; consequently protective efficacy wanes
      within a few years of immunisation. The overall outcome of the immunisation
      program will reflect both the immunogenicity of the vaccine and the uptake of the
      vaccine by the target population. The especially high incidence of meningococcal
      disease in Pacific and Maori children means that particular efforts will need to
      be made to reach these groups.

PMID- 15475987
TI  - Living with HIV in New Zealand: balancing health and quality of life.
AB  - AIM: This paper characterises the health and wellbeing of HIV-positive people in
      New Zealand. METHODS: The HIV Futures New Zealand Survey is a self-complete
      anonymous questionnaire distributed in a variety of ways. Data were collected on
      health, clinical, and social variables. RESULTS: There were 226 responses,
      estimated to be approximately 25% of the HIV positive population. Respondents
      were aged between 18 and 68, and 56% were homosexual men. Most (68%) reported a
      viral load on most recent test of below 500 copies/mL and 59% had a CD4
      lymphocyte count on most recent test of over 250 cells/mcL. However, 28% reported
      a major health condition in addition to HIV and 21% had a mental health
      condition. Most respondents (64%) were currently using antiretroviral therapy.
      Many (84%) knew other people with HIV and had contact with an HIV/AIDS
      organisation (77%). Forty-two percent of respondents had stopped working because
      of HIV, and 47% reported their main source of income as a Government benefit.
      CONCLUSIONS: This research has demonstrated that, while the HIV-positive
      population of New Zealand generally has improved health as a result of
      antiretroviral therapy, there are still significant social and economic barriers
      to their quality of life.

PMID- 15475988
TI  - Acne prevalence in secondary school students and their perceived difficulty in
      accessing acne treatment.
AB  - AIMS: To describe the epidemiology of acne in New Zealand adolescents and their
      access to acne treatment. METHODS: Secondary analysis of data collected in the
      'Youth2000' survey. A random sample of 12,934 Year 9-13 students, from 133
      secondary schools across New Zealand, was invited to participate. The survey
      included items asking about self-perceived acne and access to acne treatment.
      RESULTS: The 'Youth2000' school response rate was 85.7%, the student response
      rate 75.0%, and the overall response rate 64.3%. Of the 9570 students who
      completed the questions on acne, 67.3% reported having acne. 'Problem acne' was
      reported by 14.1% of students and was more frequently reported by female,
      Pacific, and older students. Students with 'problem acne' (as well as female,
      Maori, and Pacific students) were significantly more likely to report difficulty
      accessing medical treatment for acne (46.0% vs 13.3%; OR 5.29). These differences
      persisted after controlling for socioeconomic factors. CONCLUSIONS: Acne is
      perceived as a significant health problem by nearly 1 in 7 adolescents. For those
      with 'problem acne,' effective treatment is available but not necessarily
      accessible. There are also disparities in access to treatment, particularly for
      females, Maori, and Pacific ethnic groups. This important youth health issue
      needs to be addressed.

PMID- 15475989
TI  - A community and workplace outbreak of tuberculosis in Hawke's Bay in 2002.
AB  - AIMS: To describe a community and workplace outbreak of tuberculosis in Hawke's
      Bay in 2002. METHODS: Contact tracing and case definitions used in this study
      followed New Zealand guidelines for tuberculosis control. DNA fingerprinting of
      Mycobacterium tuberculosis isolates was performed by restriction fragment length
      polymorphism (RFLP). RESULTS: 19 new cases of active tuberculosis disease (TBD)
      and 42 cases of latent tuberculosis infection (LTBI) were diagnosed. 55 family
      and close associates of the index case were investigated, of whom 9 (16.4%) had
      TBD disease and 11 (20.0%) had LTBI. 139 co-workers on the same work shift were
      investigated of whom 8 (5.8%) had TBD and 27 (19.4%) had LTBI. DNA typing of
      Mycobacterium isolates (from 4 TBD cases) confirmed that this was an outbreak of
      'Rangipo'-strain TB. CONCLUSIONS: High infection rates were observed among
      family, close associates, and workplace contacts. Several factors may have
      contributed to this high infection rate--ie, delays in presentation and contact
      tracing, the use of positive pressure ventilation and re-circulated unfiltered
      air, and virulence of this strain of Mycobacterium tuberculosis. Inadequate
      adherence to TBD treatment precipitated this outbreak and reinforces the
      recommendation that TBD cases (in whom risk factors for non-adherence are
      present) should receive directly observed therapy (DOT) or at least by close
      supervision. Further research into strain characteristics is required in order to
      determine if the Rangipo-strain of TB is truly more virulent and if contact
      tracing or treatment regimes need to be modified accordingly.

PMID- 15475990
TI  - Outpatient Parenteral Antimicrobial Therapy (OPAT): a review of experience at
      Auckland Hospital.
AB  - AIM: To review the Auckland Hospital Outpatient Parenteral Antimicrobial Therapy
      (OPAT) Service. METHODS: Patients (>15 years of age) were referred to the Service
      and assessed for suitability for outpatient therapy by an infectious diseases
      physician and a specialist nurse. Patient demographics, referring service, site
      of infection, and infecting organism, antimicrobial agent/s and outcomes of
      treatment including complications were recorded. RESULTS: Over a 20-month period
      100 patients were treated with 107 courses of outpatient parenteral antibiotic
      therapy. Bone and joint infections accounted for close to two thirds (60%) of the
      referrals; discitis/osteomyelitis (36%), septic arthritis (14%) and infected
      metalware/prosthetic joint infections (10%). Staphylococcus aureus was the most
      frequently isolated organism (42%), and in 21% of cases no organism was
      identified. In general, antibiotics prescribed were narrow spectrum and all but
      six patients self-administered up to four times daily. Eighty-eight percent of
      treatment courses resulted in a cure. Complications related to therapy occurred
      in 35% of patients. CONCLUSIONS: We have found that parenteral antibiotic therapy
      can be administered safely and successfully in an outpatient setting despite
      relatively frequent dosing intervals. The majority of complications were minor,
      and 88% of patients were cured.

PMID- 15475992
TI  - Antibiotic resistance in Helicobacter pylori: is it a problem in New Zealand?
AB  - AIMS: Infection with Helicobacter pylori requires antibiotic treatment when
      associated with upper gastrointestinal symptoms. Antibiotic susceptibility tests
      on this pathogen are rarely carried out and there is little information available
      on the incidence of antibiotic resistant strains in New Zealand. The aim of this
      study was to assess the susceptibility of H. pylori (cultured from gastric
      biopsies in Dunedin) to antibiotics that are commonly used in treatment. METHODS:
      Over a 13-month period, gastric biopsies were obtained from selected patients
      undergoing endoscopy at Dunedin Public Hospital because of upper gastrointestinal
      symptoms. Biopsies were cultured for H. pylori and examined histologically. Fifty
      isolates from 50 patients with histological findings compatible with H. pylori
      infection were tested for sensitivity to metronidazole, clarithromycin,
      amoxycillin, and tetracycline using the epsilometer (E-) test. RESULTS:
      Metronidazole resistance was detected in 10 (20%) isolates. These isolates were
      highly resistant to metronidazole and were not inhibited by 250 mg/L. Resistance
      to clarithromycin, amoxycillin, and doxycycline was not detected. CONCLUSIONS:
      Clinicians should be aware that resistance to metronidazole appears to be common
      in H. pylori in New Zealand and that treatment regimens including this antibiotic
      may be less effective as a result. Although clarithromycin resistance was not
      detected, it is becoming increasingly problematical overseas and has been
      recorded in Auckland.

PMID- 15475991
TI  - Review of 65 cases of infective endocarditis in Dunedin Public Hospital.
AB  - BACKGROUND AND AIM: Infective endocarditis remains a challenging disease to
      manage. The objective of this study was to evaluate the management of patients
      diagnosed with infective endocarditis presenting to a regional hospital. METHODS:
      During the years 1997 to 2002, 65 episodes of bacterial endocarditis in 62
      patients (20 female, 42 male; age range from 7-89 yrs, median 68 yrs) classified
      as definite or possible according to the Duke criteria were reviewed
      retrospectively. The demographic data, predisposing factors, echocardiographic
      findings, culture results, complications and mortality were recorded and
      analysed. RESULTS: Forty-five episodes (69%) were definite endocarditis and 20
      episodes (31%) were possible endocarditis. All cases had undergone transthoracic
      or transoesophageal echocardiograms with vegetations found in 59 (91%) episodes.
      There were 49 cases of native valve endocarditis, 21 (34%) of whom had either
      congenital or acquired valvular disease. Fifteen cases (23%) were prosthetic
      valve endocarditis. One case was automated implantable cardioverter defibrillator
      leads endocarditis. Preceding dental or surgical manipulation was observed in 7
      cases (11%). Aortic valve (38/59, 64%) was the most common valve involved
      followed by mitral valve (21/59, 36%). Staphylococcus aureus accounted for 20
      episodes (31%), Streptococcus viridans for 16 episodes (25%), Enterococcus
      faecalis for 5 episodes (8%), other organisms for 9 episodes (14%), and culture
      negative endocarditis (CNE) for 15 episodes (23%). The majority of the cases had
      single valve involvement (50/59, 85%); only 9 cases (15%) were double valve
      endocarditis. Ten cases (15%) needed urgent valve replacement. The overall in
      hospital mortality rate was 20% (13/65), and at 6 months was 31% (20/65). Higher
      6-month mortality was seen in patients with Staphylococcus aureus endocarditis or
      CNE. CONCLUSIONS: Despite major advances in diagnostic technology, improvement in
      antimicrobial selection and monitoring, and progress in surgical techniques, the
      morbidity and mortality of bacterial endocarditis remain high.

PMID- 15475993
TI  - The prevention of early-onset neonatal group B streptococcus infection: technical
      report from the New Zealand GBS Consensus Working Party.
AB  - AIMS: Early-onset neonatal group B streptococcus (GBS) is the leading infectious
      cause of disease in newborn babies. Since intrapartum antibiotics interrupt
      vertical GBS transmission, this is now a largely preventable public health
      problem. An important first step is to develop (then implement) nationally,
      agreed prevention policies. METHODS: Representatives from the New Zealand College
      of Midwives, the Paediatric Society of New Zealand, the New Zealand Committee of
      the Royal Australian and New Zealand College of Obstetricians and Gynaecologists,
      the Royal New Zealand College of General Practitioners, and the Homebirth
      Association met to review evidence that will assist in the formulation of GBS
      prevention policies that are most suitable for New Zealand. RESULTS: The
      Technical Working Group noted that (i) no strategy will prevent all cases of
      early-onset GBS infection, (ii) intrapartum antibiotics are associated with rare,
      but serious, adverse effects, (iii) concerns remain over developing antibiotic
      resistance, (iv) an economic analysis is required to help inform policy, (iv)
      reliable bedside diagnostic tests for GBS in early labour are not yet available
      and (iv) the most important determinant of effectiveness will be compliance with
      a single national prevention policy. CONCLUSIONS: As an interim measure a GBS
      risk-based prevention strategy is recommended. This exposes the least numbers of
      women and their babies to antibiotics, while virtually preventing all deaths from
      GBS sepsis. Continuing education of health professionals and pregnant women,
      auditing protocol compliance, tracking adverse events amongst pregnant women, and
      national surveillance of neonatal sepsis and mortality rates and antibiotic
      resistance are necessary for the strategy's success.

PMID- 15475994
TI  - Medical image. Erosion of a vascular prostheses by the duodenum.

PMID- 15475995
TI  - Haemorrhagic meningococcal meningitis: is it scurvy?

PMID- 15475996
TI  - Antenatal screening for HIV: why are we still waiting?

PMID- 15475997
TI  - Acute coronary syndromes.

PMID- 15475998
TI  - Skin infections of the limbs of Polynesian children.

PMID- 15475999
TI  - Sub-clinical osteomalacia.

PMID- 15476000
TI  - Osteomalacia.

PMID- 15476001
TI  - In support of the consent process for organ donation from deceased persons.

PMID- 15476002
TI  - Trauma: still a problem in New Zealand.

PMID- 15476003
TI  - Dog bite injuries.
AB  - AIMS: To describe the extent of the dog bite problem in New Zealand for the
      period 1989 to 2001. METHODS: Fatalities and cases requiring public-hospital
      treatment identified from the New Zealand Health Information Service databases.
      RESULTS: There was one fatality and 3119 hospitalisations, an average of 240 per
      year. Those most at risk were males and children under 9 years of age. The
      incidence rate of dog bites has continued to increase from that reported
      previously. There has been a increase in recent years but it is difficult to
      determine whether this is real effect or an artefact of coding. CONCLUSIONS: Dog
      bite injuries represent a significant public health problem in New Zealand.
      Ongoing monitoring is required to determine if dog control policies are having
      the intended effect.

PMID- 15476004
TI  - Co-morbidities in trauma patients: common and significant.
AB  - INTRODUCTION: Trauma is a heterogeneous 'disease' that affects all age groups
      with varying degrees of severity. While injury severity, time to definitive care,
      and the quality of care in trauma patients have been quantified, it has been much
      more difficult to quantify pre-existing health status or 'host factors' in trauma
      patients and relate them to trauma outcome. Numerous studies have attempted this
      task, but none have succeeded in producing a simple system to quantify co
      morbidities. As a prelude to developing a simple Abbreviated injury scale (AIS)
      like score, the incidence of major and minor co-morbidities (and outcomes) in a
      cohort of admitted trauma patients > or =40 years of age were evaluated. METHODS:
      A prospective review of the Auckland Trauma Registry of trauma patients age > or
      =40 years that were admitted to Auckland Hospital between 1 January 2003 and 3
      March 2003 was performed. Among the data collected were the patient's co
      morbidities. The co-morbidities were divided into major and minor co-morbidities:
      major co-morbidities were defined by criteria found in the APACHE 2 PIC system,
      whereas minor co-morbidities were all the other co-morbidities not included in
      the APACHE 2 PIC system. RESULTS: A total of 105 patients were included. There
      were 57 males and 48 females in this study. Overall, 71% of the population had
      pre-existing co-morbid conditions, with 23% having a major co-morbid condition.
      Major trauma [injury severity score (ISS) of 15] was seen to decrease as age
      increases. The mortality rate in this group of patients was 4.7%. DISCUSSION: Co
      morbidities were surprisingly common in trauma patients. Trauma outcome in
      patients with co-morbidities is difficult to predict and is not well addressed by
      any of the existing injury scales. The possibility of developing single 'AIS
      like' co-morbidity score merits ongoing evaluation. The prevalence of co
      morbidities in trauma patients > or =40 years of age suggests that the influence
      of co-morbidity on outcome should be considered in a much greater cohort than is
      currently the case.

PMID- 15476005
TI  - Head injury and associated maxillofacial injuries.
AB  - AIMS: To review patients admitted with head injuries under a regional
      neurosurgical service, to document the incidence and features of associated
      maxillofacial trauma, and to assess any delay in referral to a maxillofacial
      surgeon for definitive management of facial injuries. METHODS: The details of all
      patients admitted under the neurosurgical service at Christchurch Hospital over
      the preceding 7 years (1995-2002) were reviewed via that department's database.
      The records of those patients noted to have a maxillofacial injury were
      requested, and the following data obtained: demographics, diagnosis, and mode of
      injury (including specific variables such as alcohol consumption and seatbelt
      usage in motor vehicle accidents). RESULTS: 2307 patients were admitted under the
      neurosurgical service at Christchurch Hospital over a 7-year period. Five percent
      of those patients had an associated maxillofacial injury. Three-quarters were
      men, with an average age of 27 years. Motor vehicle accidents and assaults were
      the most common cause of injury. Nearly one-third of those persons in motor
      vehicle accidents were not wearing seatbelts. Alcohol was more frequently
      involved in mild and moderate head injuries and these patients were more likely
      to have been assaulted than those admitted with severe head injuries. There were
      no significant delays in referring patients admitted who had an associated
      maxillofacial injury to a maxillofacial surgeon. CONCLUSIONS: A small but
      significant number of patients admitted with head injuries will have an
      associated maxillofacial injury.

PMID- 15476006
TI  - Information provision after mild traumatic brain injury (MTBI): a survey of
      general practitioners and hospitals in New Zealand.
AB  - AIMS: To determine the nature, extent, and quality of information provided by
      general practitioners (GPs) and hospital emergency departments to people after
      mild traumatic brain injury (MTBI). METHOD: A survey was distributed throughout
      New Zealand to a representative sample of GPs and emergency departments (EDs).
      RESULTS: 244 valid surveys were returned, (229 from GPs and 15 from EDs), giving
      a return rate of 50.1%. Included with the returned surveys were 145 samples of
      information that these agencies typically provide after MTBI. Overall, 45.9% of
      respondents (93.4% of EDs and 42.8% of GPs) provided an information sheet to
      patients with a confirmed or suspected MTBI. These generally covered signs and
      symptoms; when to seek medical attention; and advice about pain relief, driving,
      alcohol, and rest. Of the information sheets provided by EDs, 92.9% had a FRE
      score of over 61 (the level recommended to be able to be read by 70% of the
      population), compared to 56% of those provided by GPs. Information sheets ranged
      in length from half a page to 10 pages, with those provided by EDs generally
      longer than those provided by GPs (mean 33.6 compared to 12.9 sentences).
      CONCLUSIONS: Less than half of the GPs who returned questionnaires routinely
      provided information sheets about head injury and what to expect. Of the sample
      information sheets that were returned, just under half did not meet the criteria
      for being able to be read by 70% of the population.

PMID- 15476007
TI  - Infantile subdural haematoma in Auckland, New Zealand: 1988-1998.
AB  - AIM: To review the Auckland experience of traumatic subdural haematoma (SDH) in
      infants under 2 years of age, with particular regard to features which might help
      to differentiate accidental from non-accidental injury (NAI). METHODS:
      Retrospective review of the medical records of children under 2 years of age,
      coded for subdural haematoma (SDH) and retinal haemorrhage (RH) over a 10-year
      period. RESULTS: Sixty-four cases of SDH were identified. Forty-one of these were
      due to non-accidental trauma, and 23 cases were accidental. Differences between
      these two groups related to the age of presentation, ethnicity, the type of
      explanation for the injury, and differences in aspects of the clinical
      presentation (apnoea, seizures, fractures, retinal haemorrhage). Mortality in the
      non-accidental group was far higher. CONCLUSIONS: Subdural haemorrhage is a
      significant cause of death and disability in infants presenting to hospital in
      Auckland. In the majority of cases, it is caused by child abuse, and there are
      certain features that are helpful in establishing this diagnosis. The long-term
      outcome in this group is unknown, but there is reason to believe that, in many
      cases, it is poor. There is considerable scope for further research.

PMID- 15476008
TI  - Vascular trauma in New Zealand: an 11-year review of NZVASC, the New Zealand
      Society of Vascular Surgeons' audit database.
AB  - AIM: To describe vascular trauma in New Zealand: its management and early
      outcomes. METHODS: Patients suffering vascular trauma between January 1993 and
      December 2003 were analysed using data collected prospectively by the New Zealand
      Society of Vascular Surgeons' database (NZVASC). RESULTS: There were 549 cases of
      vascular trauma amongst 45,759 vascular admissions collected by the database in
      the 11-year period. This study confirmed the findings in international studies
      that younger adult males were more likely to suffer vascular trauma. Elderly
      patients, especially females, were most at risk of iatrogenic vascular injury,
      which accounted for 22% of cases in this study. Complication rates reported by
      rural vascular surgeons in New Zealand were comparable to results in the main
      centres and to international reports. CONCLUSION: While programmes to slow down
      and sober up road users help reduce injuries in the younger age groups, it lies
      in the hands of our own profession to reduce the iatrogenic injuries in the older
      patients.

PMID- 15476009
TI  - Cost analysis of traditional follow-up protocol versus MRI for radiographically
      occult scaphoid fractures: a pilot study for the Accident Compensation
      Corporation.
AB  - AIMS: Assessment of the cost-effectiveness of early magnetic resonance imaging
      (MRI) for suspected radiographically occult scaphoid fractures. Methods Compare
      costs of patients presenting acutely with suspected scaphoid injuries (managed
      either with traditional follow-up radiographs and plasters) versus early MRI to
      exclude a fracture. Results The average medical cost for the control group was
      NZ470 dollars versus NZ533 dollars in the MRI group. The cost to exclude a
      fracture was NZ437 dollars with MRI versus NZ459 dollars for the traditional
      protocol. Weekly compensation costs were comparable. Conclusions The early
      diagnosis of clinical scaphoid fractures has clear clinical advantages. The use
      of MRI in this situation is cost-effective, and we recommend that it be offered
      as part of the routine investigative work-up available for this difficult, but
      common, clinical scenario.

PMID- 15476010
TI  - Reform of ACC Medical Misadventure.

PMID- 15476011
TI  - Over my dead body: the ethics of organ donation in New Zealand.

PMID- 15476012
TI  - Impact of concomitant trauma in the management of blunt splenic injuries.
AB  - AIMS: Conservative management of isolated blunt splenic injuries has become
      widely accepted for haemodynamically stable patients, but may be untenable in
      those with multiple injuries. A retrospective review was performed to evaluate of
      our cumulative experience with non-operative management of splenic injuries, and
      to identify the risk factors for operative management. METHODS: Eighty patients
      were identified. Demographics, mechanism of injury, injury severity score (ISS),
      clinical signs at presentation, utility of computed tomography scans and methods
      of treatment (operative management vs conservative management) were documented
      and statistically analysed to identify predictors for operative management.
      RESULTS: Initially, 45 patients (56%) were managed without operation, while 35
      patients underwent urgent laparotomy - with 26 (74% in operative group) of these
      having splenectomy performed. Two patients (out of 45) failed conservative
      management and required delayed splenectomy, a 96% success rate for intended
      conservative management. Thus, overall rates of 54% non-operative management and
      65% splenic conservation were achieved. The mean ISS of the operative management
      group (ISS=30) was higher than that of the non-operative treatment group (ISS=13,
      p<0.05), reflecting not only the grade of the splenic injury but also the
      severity of concomitant trauma. Risk factors for patients with blunt splenic
      injuries requiring operative management include ISS > or =16, hypotension, GCS <
      or =13, and requirement for blood transfusion (p<0.05). CONCLUSIONS: Appropriate
      patient selection is the most important element of non-operative management.
      Patients with splenic injuries who are haemodynamically stable can be managed non
      operatively with acceptable outcome. However, in the presence of concomitant
      trauma, there is an increasing trend towards operative management.

PMID- 15476013
TI  - Clinical trial registration: a statement from the International Committee of
      Medical Journal Editors.

PMID- 15476014
TI  - Meningitis: tragedy, culture, and blame.

PMID- 15476015
TI  - Skin infections of the limbs of Polynesian children.

PMID- 15476016
TI  - Skin infections of the limbs of Polynesian children.

PMID- 15476017
TI  - Antifungal susceptibility of non-albicans Candida species causing fingernail
      onychomycosis.

PMID- 15476018
TI  - Sudden Infant Death Syndrome (SIDS).

PMID- 15476019
TI  - Physiology, pseudoscience, and Buteyko.

PMID- 15476020
TI  - Population need and geographical access to general practitioners in rural New
      Zealand.

PMID- 15476021
TI  - Acute coronary syndromes.

PMID- 15476050
TI  - Use of selective media for detection of cephalothin-resistant bacteria in
      surgical patients.
AB  - Bacterial colonization in hospitalized patients is an important step in
      nosocomial infections. Frequent employment of antimicrobials can modify patients'
      normal microbiota, favoring colonization and infection by antimicrobial-resistant
      microorganisms. First-generation cephalosporins are frequently used as
      prophylactic antibiotics in surgery. Intestinal, oropharyngeal and skin
      colonization by cephalothin-resistant microorganisms were studied in 60 pre
      operative patients at the Hospital Universitario Pedro Ernesto. Feces were
      cultured in Eosin-methylene blue medium containing 32 microg/mL of cephalothin.
      Swabs obtained from the oropharynx and from skin were inoculated in cistein
      lactose electrolytes-deficient medium containing 32 microg/mL of cephalothin.
      Isolated strains were identified and tested for susceptibility to antimicrobials
      by disk diffusion. Cephalothin-resistant strains were isolated from the feces of
      59 patients (98%), from the oropharynx of 13 patients (22%) and from skin in 10
      patients (17%). Enterobacter cloacae was predominant in feces (68% of the
      patients) and oropharynx (13%). Acinetobacter spp. was the most frequent
      microorganism isolated from the skin (10%). Antimicrobial multiresistant strains
      were isolated from at least one of the sites in 38 patients (63%). The employment
      of selective medium containing antimicrobials is a relatively simple and
      efficient method, being useful to evaluate microorganisms from hospitalized
      patients' microbiota that are relevant as potential pathogens in nosocomial
      infections.

PMID- 15476051
TI  - Molecular epidemiology and antimicrobial susceptibility of Enterococci recovered
      from Brazilian intensive care units.
AB  - We studied the antimicrobial resistance and the molecular epidemiology of 99
      enterococcal surveillance isolates from two hospitals of Brasilia, Brazil.
      Conventional biochemical tests were used to identify the enterococcal species and
      the disk diffusion method was used to determine their resistance profiles.
      Enterococcus faecalis (76%) and E. faecium (9%) were the most prevalent species.
      No enterococci showed the vanA or vanB vancomycin resistance phenotypes or
      genotypes. Only the intrinsically resistant species E. gallinarum (n=2) and E.
      casseliflavus (n=3) harbored the vancomycin-resistance genes vanC1 and vanC2/3,
      respectively. We found E. faecalis isolates with high-level resistance to
      gentamicin (22%) and streptomycin (8%) and both E. faecalis and E. faecium
      isolates with resistance to more than two antimicrobials (84% and 67%,
      respectively). Nine E. faecalis isolates (12%) were resistant to ampicillin; the
      minimal inhibitory concentration (MIC) values were 16 microg/mL (n=6) and 32
      microg/mL (n=3). Among these ampicillin-resistant E. faecalis, seven were also
      resistant to gentamicin, ciprofloxacin, rifampin, penicillin, chloramphenicol,
      tetracycline and erythromycin. Pulsed-field gel electrophoresis classified those
      isolates in three different genotypes, suggesting dissemination of genetically
      related ampicillin-resistant E. faecalis strains among different patients.

PMID- 15476052
TI  - Hospital gowns as a vehicle for bacterial dissemination in an intensive care
      unit.
AB  - The microbiota from the uniforms of 31 professionals from the general intensive
      care unit was analyzed. The samples were collected in duplicate at the beginning
      and at the end of the work period. Total viable counts of microorganisms were
      determined; there was a significant increase in the counts at the end of the
      period, when compared with those obtained at the beginning. No significant
      difference was observed between the first and second counts obtained from the
      cuffs. However, differences were observed for the samples from the abdominal
      region. Among the isolated pathogens 11/18 were Staphylococcus aureus, 2/18 were
      Acinetobacter baumannii, 2/18 were Klebsiela pneumoniae and 1/18 were Serratia
      rubidae. Some of these isolates were multi-resistant to antibiotics. Emphasis
      should be placed on reducing the spread of these pathogens in the hospital,
      making sure that biosafety protocols are followed by the staff.

PMID- 15476053
TI  - Efficacy and safety of Efavirenz in HIV patients on Rifampin for tuberculosis.
AB  - Forty-nine AIDS patients, most of who were antiretroviral therapy (ARV) naive,
      with active tuberculosis, were treated with Rifampin 600 mg, Isoniazid 400 mg and
      Pirazinamide 2 g daily. They also received ARV, consisting of Efavirenz (600
      mg/day) plus 2 NRTIs. All patients were prospectively followed for at least 24
      months. Baselines were: male/female ratio 2:1, mean age 34.7 +/- 9.4 yrs; weight
      51 +/- 9.0 kg, viral load 5.6 +/- 0.6 logs, CD4 cell count 101 +/- 128 cells/
      mm3. Follow up mean values of data logs of VL and CD4+ cell /mm3 counts were: VL
      1.7 and CD4+ 265; VL 1.3 and CD4+ 251; VL 1.4 and CD4+ 326 at 6, 12 and 24
      months, respectively. Weight gain changes were: 5 +/- 9.9 +/- 12 and 21 +/- 16 kg
      respectively at 6, 12 and 24 months. A non-concomitant ARV regimen was introduced
      at least three weeks after TB treatment initiation. Severe adverse reactions
      included rash (two), toxic hepatitis (six), Immune Reconstitution Syndrome
      (seven), and four deaths. We conclude that Efavirenz at a daily dose of 600 mg is
      sufficient and safe to treat HIV/TB patients using a Rifampin containing regimen.

PMID- 15476054
TI  - Antifungal treatment with carvacrol and eugenol of oral candidiasis in
      immunosuppressed rats.
AB  - Carvacrol and eugenol, the main (phenolic) components of essential oils of some
      aromatic plants, were evaluated for their therapeutic efficacy in the treatment
      of experimental oral candidiasis induced by Candida albicans in immunosuppressed
      rats. This anticandidal activity was analyzed by microbiological and
      histopathological techniques, and it was compared with that of nystatin, which
      was used as a positive control. Microbiologically, carvacrol and eugenol
      significantly (p<0.05) reduced the number of colony forming units (CFU) sampled
      from the oral cavity of rats treated for eight consecutive days, compared to
      untreated control rats. Treatment with nystatin gave similar results.
      Histologically, the untreated control animals showed numerous hyphae on the
      epithelium of the dorsal surface of the tongue. In contrast no hyphal
      colonization of the epithelium was seen in carvacrol-treated animals, while in
      rats treated with eugenol, only a few focalized zones of the dorsal surface of
      the tongue were occupied by hyphae. In the nystatin treated group, hyphae were
      found in the folds of the tongue mucosa. Thus, the histological data were
      confirmed by the microbiological tests for carvacrol and eugenol, but not for the
      nystatin-treated group. Therefore, carvacrol and eugenol could be considered as
      strong antifungal agents and could be proposed as therapeutic agents for oral
      candidiasis.

PMID- 15476055
TI  - Transfusion risk for hepatitis B, hepatitis C and HIV in the state of Santa
      Catarina, Brazil, 1991-2001.
AB  - We examined the time trend of residual risk of transfusing blood contaminated
      with HIV, hepatitis B and hepatitis C, in the largest blood bank of the state of
      Santa Catarina, Brazil, 1991-2001. The HIV risk was reduced approximately 10
      times during the decade of 1990, to 1:48777, but then increased significantly by
      the end of 2001. A similar time trend was observed for hepatitis B and hepatitis
      C, although the increase was not significant in this case. Even during the period
      of lowest risk, the estimates were considerably higher than in developed
      countries.

PMID- 15476056
TI  - Three decades of meningococcal disease in the state of Santa Catarina, Brazil.
AB  - Consolidation of data on meningococcal disease surveillance for the state of
      Santa Catarina, Brazil, has provided new insight about the evolution of this
      disease during the period of 1971-2000. A descriptive epidemiological study,
      based on retrospective analysis of all cases of meningococcal disease notified in
      the state of Santa Catarina, linked the surveillance data from the Secretary of
      the State of Health, magnetic tape records and the data from the national
      surveillance of diseases of obligatory notification. Following World Health
      Organization guidelines, cumulative incidence exceeding five cases per 100,000
      inhabitants was considered indicative of an epidemic. Official population data
      from the Fundacao Instituto Brasileiro de Geografia e Estatistica were used for
      the incidence denominator. During the 1971-2000 period, 7,893 cases and 1,354
      deaths caused by meningococcal disease were reported. This corresponds to a mean
      of 263 cases and 45 deaths per year, with a mean incidence of 6.4 cases per
      100,000 inhabitants and a fatality rate of 17.2%. Three distinct epidemiological
      periods were identified, two of which can be considered epidemic. Two of three
      distinct epidemiological periods were characterized by an epidemic of
      meningococcal disease, covering 20 of the 30 years analyzed. Identification of
      the epidemics and preventive actions, such as vaccination and health education,
      contributed to the reduction of morbidity and mortality due to this disease.

PMID- 15476057
TI  - Avidity of IgG for rubella: an evaluation of the need for implementation at the
      Materno-Infantil Presidente Vargas Hospital in Porto Alegre, Rio Grande do Sul,
      Brazil.
AB  - Rubella serum assays performed in the laboratory of the Materno-Infantil
      Presidente Vargas Hospital (HMIPV) from 1998 to 2002 were reviewed to determine
      if IgG avidity assays should be implemented. IgG was determined using the Enzyme
      Linked Fluorescent Assay, ELFA, VIDAS system, bioMerieux or the Microparticle
      Enzyme Immunoassay, MEIA, Axsym system, Abbott, and IgM was determined using the
      ELFA, VIDAS system, bioMerieux, a capture format assay. Specific IgG was assayed
      in 2,863 samples, with positive results for 84% of the patients, for the most
      part with high levels of antibodies. IgM was assayed in 2,851 samples, being
      positive in 14 (0.49%) and inconclusive in 25 (0.88%). Serology for toxoplasmosis
      was also positive or inconclusive in 5 patients. After a cost-effectiveness
      analysis, it was decided not to implement avidity assays, considering that the
      HMIPV is a public institution, with limited funding. Difficulties concerning the
      integration of the Clinical Pathology Service with the Clinical Staff of the
      institution were also considered.

PMID- 15476058
TI  - Varicella-zoster virus encephalitis in an AIDS patient.
AB  - A 37-year-old man with a three-year history of Acquired Immunodeficiency Syndrome
      was admitted with impaired consciousness, seizures and fever. He was on highly
      active antiretroviral therapy and on neurotoxoplasmosis secondary prophylaxis.
      Laboratory exams from two months before showed a CD4 cell count of 37/microL and
      a viral load of 230,000 copies/mL. Three months before admission he developed
      herpetic skin rash in the right trunk and acyclovir was added to his treatment
      regimen. On physical exam he was drowsy and had motor and sensory aphasia. The
      patient had elevated protein levels and normal pressure in the cerebrospinal
      fluid (CSF). Contrast enhanced computed tomography scan of the brain showed a
      hypodense lesion in the left parietal lobe, with poorly defined margins and no
      contrast enhancement. The magnetic resonance scan (MRI) showed multiple
      hyperintensities in T2-weighted image in white and grey matters and hypointense
      products of hemorrhage in both hemispheres and in the cerebellum. He was
      empirically treated with intravenous acyclovir and prednisone. Viral DNA of
      Varicella-zoster virus (VZV) was detected in the CSF by means of polymerase chain
      reaction (PCR) analysis. Acyclovir was continued for 10 days and the patient
      became well, with improvement of aphasia. We present a case of VZV encephalitis,
      confirmed by nested PCR, in a patient with suggestive MRI findings, who succeeded
      with treatment. VZV encephalitis is a rare opportunistic infection, occurring in
      0.1 to 4% of AIDS patients with neurological disease; it is related to severe
      immunodeficiency and has a high mortality.

PMID- 15476059
TI  - Human ehrlichioses in Brazil: first suspect cases.
AB  - Brazilian spotted fever (BSF) rickettsiosis is the most common and recognized of
      the human rickettsioses in Brazil. It is difficult to establish the diagnosis of
      human rickettsiosis infection by routine microbiologic methods, creating a false
      idea that Rickettsia and Ehrlichia infections are rare and without importance.
      New tick-borne diseases, like human granulocytic anaplasmosis (HGA) and human
      monocytic ehrlichiosis (HME), have been described in many countries. These
      diseases can present symptoms similar to rickettsioses of the spotted fever
      group, and they are transmitted by ixodid ticks. The first two suspected cases of
      human ehrlichiosis in Brazil were first considered to be cases of BSF. The
      differential diagnosis was made at the Minas Gerais Rickettsiosis Public Health
      Laboratory. The clinical and laboratory findings, with positive serology for the
      HME agent, indicated suspected cases of human ehrlichioses in Brazil.

PMID- 15476060
TI  - Acute hemiplegia associated with cat-scratch disease.
AB  - Cat scratch disease (CSD) is an infectious illness caused by a Gram-negative rod
      named Bartonella henselae. Typical CSD is characterized by a small skin lesion at
      the site of a scratch or a bite, followed by regional lymphadenopathy, one to two
      weeks later. Atypical forms may present as ocular manifestations, neurological
      manifestations, hepatosplenic involvement and vertebral osteomyelitis. Among
      neurological complications, encephalopathy is by far the most common. Other
      neurological manifestations are very rare. We report a case of an 11-year-old
      boy, with a posterior cervical lymphadenopathy and fever. Cat scratch disease was
      diagnosed and treated after a positive "Whartin-Starry" stain on lymph node
      biopsy. Two weeks after treatment, the patient was readmitted presenting an acute
      episode of left hemiplegia. A brain MRI demonstrated a right subcortical fronto
      parietal lesion with no contrast enhancement. Complete recovery was observed
      after corticosteroid treatment.

PMID- 15476061
TI  - Pediatric knowledge about acute viral hepatitis.
AB  - Knowledge about hepatotropic viruses is crucial for pediatricians because of the
      high prevalence of viral hepatitis during childhood. The multiplicity of
      hepatotropic viruses, the spectrum of acute and chronic infections, and the
      sequels of viral hepatitis result in a need for physicians to better understand
      the clinical and epidemiological context of patients with viral hepatitis, as
      well as the importance of prevention measures for hepatitis. A descriptive cross
      sectional study was made of pediatrician's knowledge about viral hepatitis,
      through questionnaires to 574 pediatricians, with no obligation of
      identification. The pediatricians were recruited among those who attended a
      national Congress of Pediatrics in Brasilia, Brazil. Among these pediatricians,
      50.1% frequently treated cases of hepatitis, and 74.7% indicated that they had
      knowledge of the existence of five hepatotropic viruses; 14.5% knew about at
      least four types of hepatitis complications, while only 7.7% and 4.3% were able
      to correctly diagnose viral hepatitis A and B, respectively. Many (28.4%) did not
      know how to treat the patients adequately. Only 37.5% had already recommended
      vaccination against hepatitis B. Only 50.2% of the pediatricians had been
      vaccinated against hepatitis B. We concluded that it is crucial to make
      pediatricians more knowledgeable about viral hepatitis, through continued
      education programs, especially emphasizing prevention procedures.

PMID- 15476062
TI  - Hyperphosphorylated tau protein in the cerebrospinal fluid of patients with
      Alzheimer's disease and other dementias: preliminary findings.
AB  - Alzheimer's disease (AD) is pathologically characterized by the accumulation of
      amyloid plaques and tau-associated neurofibrillary tangles in the cerebral
      tissue. The search for antemortem biomarkers is intense including analysis of
      cerebrospinal fluid (CSF) beta-amyloid and tau proteins concentrations seeking
      for an accurate and early diagnosis. Levels of hyperphosphorylated tau at
      threonine 181 were measured in the CSF of 34 patients with AD (19 with senile AD 
      SAD and eight with presenile AD - PSAD) and seven with other dementias (OD). The
      levels of CSF phosphotau were significantly higher in the AD patients compared to
      OD (AUC 0.812), with no association with severity of dementia, age of onset,
      duration of the disease or scores in the Mini-Mental State Examination. There
      were no differences of phosphotau levels between SAD and PSAD patients. These
      findings corroborate some previous studies and indicate that CSF phosphotau may
      help to differentiate AD from other dementias.

PMID- 15476063
TI  - Taenia antigens detection in the cerebrospinal fluid of patients with
      neurocysticercosis and its relationship with clinical activity of the disease.
AB  - OBJECTIVE: (1) To determine the concentration of Taenia antigens in the
      cerebrospinal fluid (CSF) of patients with neurocysticercosis (NC); (2) to
      establish its relationship with clinical activity of the disease and with
      classical variables of CSF. METHOD: A CSF examination was performed in one sample
      from 36 patients with definitive diagnosis of NC, including: quantitative and
      cytomorphological study, biochemical tests, immunological reactions for
      cysticercosis and Taenia antigens. The antibodies for antigens detection were
      obtained from the larval form of Taenia crassiceps, ORF strain. After
      intraperitoneal passage through female mice, a group of rabbits was immunized
      with vesicular fluid antigens. RESULTS: The Taenia antigen was detected in CSF
      from 17 patients (47.2%), especially in those patients with epileptic symptoms in
      the last 12 months. CONCLUSION: Taenia antigens presence in CSF have significant
      relationship with clinically active forms of NC, being a more sensitive marker
      than the classic eosinophil presence.

PMID- 15476064
TI  - Assessment of the epilepsy treatment gap in two cities of south-east of Brazil.
AB  - OBJECTIVE: To assess the epilepsy treatment gap in Campinas and Sao Josedo Rio
      Preto, two cities in the State of Sao Paulo, Brazil. METHOD: The treatment gap
      was estimated using the formula n1-n2/n1x100, where n1 was calculated using 1.86%
      prevalence and represented the number of individuals with epilepsy, while n2
      represented the number of people who could be treated with an adult standard dose
      for a year utilizing the antiepileptic drugs supplied by the public health
      system. RESULTS: Our estimates revealed that in 2001, approximately 50% of the
      population with epilepsy was treated with the recommended antiepileptic
      medication. CONCLUSION: These results suggest that a relevant percentage of
      patients with epilepsy are not untreated. Further epidemiological studies are
      needed to investigate the reasons for this treatment gap so that interventions
      can reduce this gap and improve the quality of life of patients with epilepsy.

PMID- 15476065
TI  - Analysis of the prevalence of insomnia in the adult population of Sao Jose do Rio
      Preto, Brazil.
AB  - OBJECTIVE: To establish the prevalence of insomnia in the adult urban population
      of Sao Jose do Rio Preto, Brazil and correlate it with the demographic data.
      METHOD: We evaluated 1105 individuals in to guarantee an error margin of 3% and a
      confidence level of 95% using a structured questionnaire and following the DSM-IV
      and DSM-III-R criteria, in the period from January 10 to February 28 2001.
      RESULTS: We encountered a prevalence of 32% of insomnia, which was most commonly
      seen in women, single people, from the lower economical brackets, with a low
      level of schooling and it was less associated with younger adults (18-31 year
      olds). CONCLUSION: Our findings indicate that the prevalence of insomnia in the
      adult population of Sao Jose do Rio Preto is comparable with other countries such
      as the USA and those of Europe and also with other cities in Brazil.

PMID- 15476066
TI  - Effect of episodic tension-type headache on the health-related quality of life in
      employees of a Brazilian public hospital.
AB  - OBJECTIVE: To evaluate the impact of ETTH on HRQoL in a sample of employees of a
      Brazilian public hospital. METHOD: Three hundred and sixty Mario Gatti Hospital
      employees were asked about headache occurrence in the previous 6 months and
      completed a SF-36 and a pain questionnaires concerning impact of pain (0 to 10
      scale) on daily activities, work efficiency, leisure and social activities in
      previous six months. Two groups were studied: 1. Episodic Tension-type headache
      group: 127 employees -- 81 (63.8%) female and 46 (36.2%), male. 2. CONTROL GROUP:
      124, 71 (57.3%) female and 53 (42.7%) male. RESULTS: ETTH had lowers scores than
      control in all domains of SF-36; in vitality and bodily pain the difference was
      statistically significant. CONCLUSION: Our results indicate that ETTH suffers
      have impact on HRQoL predominantly in vitality. Psychological factors associated
      to pain may explain this finding.

PMID- 15476067
TI  - Depression and migraine.
AB  - The objective of this study was to evaluate both the presence and intensity of
      depressive symptoms in patients with episodic migraine (EM) and transformed
      migraine (TM) or chronic migraine, comparing them with a control group. Beck
      Depression Inventory (BDI) was used for this purpose. The median of BDI score of
      the control group was significantly lower than the EM and TM groups (p<0.0005).
      Either the EM or the TM did not show any significant difference in relation to
      the median of BDI scores (p=0.12). The TM group showed a higher frequency of
      severe depression when analyzed qualitatively by dependence analysis. Symptoms of
      severe depression by means of qualitative analysis may strengthen a co-morbidity
      between depression and transformed migraine. This association might be considered
      rather a factor of TM perpetuation than a risk factor for the transformation of
      EM into TM.

PMID- 15476068
TI  - A longitudinal study of a neuropsychological rehabilitation program in
      Alzheimer's disease.
AB  - Our aim was to study the duration of benefits derived from a neuropsychological
      rehabilitation program (NRP) for dementia patients. METHOD: The participants in
      this study were three patients diagnosed as probable Alzheimer's disease in the
      initial-to-moderate phase; the three were taking anticholinesterases. They were
      submitted to a neuropsychological evaluation (NE) before the NRP and then
      reevaluated after 12 and 24 months of treatment. The aim of our intervention was
      to do practical work with implicit and explicit residual memory by training them
      in everyday life activities, and using compensatory strategies and their intact
      cognitive abilities. RESULTS: Analysis of quantitative NE data (descriptive
      measures) after the first year of NRP showed cognitive improvement, functional
      stabilization and fewer behavioral problems. However, this improvement did not
      continue in the second year, and the disease maintained its characteristic
      progression.

PMID- 15476069
TI  - Parkinsonism and other movement disorders in outpatients in chronic use of
      cinnarizine and flunarizine.
AB  - The purpose of this study is to determine the prevalence and the patterns of
      movement disorders (MD) in outpatients submitted to the chronic use of
      cinnarizine (cz) or flunarizine (fz), and to establish the main risk factors for
      MD development. Over a period of 3 months, data were collected from outpatients
      who were chronic users of cz or fz in a municipal health institute. A total of 26
      outpatients were included and all of them were submitted to a protocol that
      included DSM-4 diagnosis criteria for drug-induced movement disorders,
      parkinsonism (PK) and depression. Parkinsonism was diagnosed in 34% of the
      patients, PK plus akathisia, PK plus akathisia and bucco-linguo-masticatory
      syndrome (BLMS), isolated BLMS and dystonia were found in 4% patients each.
      Patients with BLMS had the highest median age and the longest average period in
      which they used the drugs. The affected group, when compared to the non-affected
      one, presented with higher rates of depression. This study demonstrates the
      existence of a direct relationship between the time of use of cz and fz, the age
      and the prevalence of PK and other MD. It also suggests that these drugs increase
      the incidence of depression.

PMID- 15476070
TI  - Computerized tomography findings in Fahr's syndrome.
AB  - We analyzed computerized tomography (CT) findings in six patients with Fahr's
      syndrome. They presented calcifications in basal ganglia, dentate nucleus,
      subcortical region and semioval center, due to alteration in calcium metabolism
      or due to senile relative hypoxemic state. The image pattern was not strictly
      related with etiology, although some differences in dystrophic senile
      calcifications (the only one present in semioval center and absent in subcortical
      region). CT is an easy exam, has maximum sensitivity and allows diagnosis,
      contributing to early treatment of many etiologies of Fahr's syndrome.

PMID- 15476071
TI  - Cerebral tuberculomas in AIDS patients: a forgotten diagnosis?
AB  - The human immunodeficiency virus (HIV) infection epidemics increased the
      prevalence, multi-drug resistance and disseminated forms of tuberculosis. The
      central nervous system (CNS) tuberculosis has high mortality and morbidity, and
      it is usually divided into diffuse (meningitis) and localized (tuberculoma and
      abscess) forms. We report three cases of cerebral tuberculomas in AIDS patients:
      one with definitive diagnosis, confirmed with histopathology, and two with
      probable diagnosis, based on clinical information, radiological images,
      Mycobaterium tuberculosis isolation out of the CNS and adequate response to
      antituberculous treatment. Further, we discuss diagnostic, therapeutic and
      prognostic issues of tuberculomas, with emphasis in the distinction from cerebral
      tuberculous abscesses. Despite of their infrequent presentation, tuberculomas
      should be considered in the differential diagnosis of cerebral expansive lesions
      in patients with AIDS.

PMID- 15476072
TI  - Auditory hypersensitivity in children and teenagers with autistic spectrum
      disorder.
AB  - OBJECTIVE: To verify if the clinical behavior of auditory hypersensitivity,
      reported in interviews with parents/caregivers and therapists/teachers of 46
      children and teenagers suffering from autistic spectrum disorder, correspond to
      audiological findings. METHOD: The clinical diagnosis for auditory
      hypersensitivity was investigated by means of an interview. Subsequently, a test
      of the acoustic stapedial reflex was conducted, and responses to intense acoustic
      stimulus in open field were observed. RESULTS: Of the 46 subjects, 11 (23.9%)
      were clinically diagnosed as oversensitive to sound and only 2 showed discomfort
      when exposed to intense acoustic stimulus in open field. There was no
      statistically significant difference for the test of the ipsilateral acoustic
      stapedial reflex between the groups. CONCLUSION: Behavioral manifestations to
      sounds are not associated to hypersensitivity of the auditory pathways, but
      instead these are associated to difficulties in the upper processing, involving
      systems that usually are impaired in autistic spectrum patients, such as the
      limbic system.

PMID- 15476073
TI  - Ischemic cerebrovascular disease in childhood: cognitive assessment of 15
      patients.
AB  - The aim of this study was to evaluate and to compare the cognitive function of
      children with ischemic cerebrovascular disease (ICVD). Fifteen children, 7 girls
      and 8 boys, aged 7.9 to 16.1 years, were evaluated by Piaget's clinical method.
      The control group was composed by fifteen children whose ages, sex and
      socioeconomic conditions were similar to those of the ICVD group. The cognitive
      function evaluation of the ICVD group showed that most of the children (10/15)
      were under their age group. The SPECT was performed on 14 children with ICVD and
      the results showed that 8/9 children with hypoperfusion presented a poor
      cognitive estimation and 3/5 children with normal perfusion demonstrated an
      adequate performance. We conclude that ICVD in childhood may compromise
      cognition; therefore, it needs a follow up of acquisitions during alI the stages
      of development.

PMID- 15476074
TI  - Clinical presentation, treatment and outcome of patients with cerebral
      metastases: the University of Sao Paulo series.
AB  - INTRODUCTION: Secondary neoplasias are the most common tumors affecting the
      central nervous system and several clinical aspects of this disease are still
      controversial. METHOD: Forty-seven consecutive patients with the diagnosis of
      cerebral metastases (CM) were retrospectively studied at the Clinical Hospital of
      Sao Paulo University Medical School. Mean age was 53.9 years and 25 patients were
      female. RESULTS: The most frequent primary sites were breast, lung and skin.
      Symptoms were related to increased intracranial pressure (ICP) in 48.9%, focal
      neurological events in 27.7% and both in 17.0%. Single brain metastases were
      found in 57.4% of those cases, the frontal lobe being most frequently affected.
      Surgical treatment was performed in 68.1%, radiotherapy in 40.4% and chemotherapy
      in 17.0%. CONCLUSION: After statistical analysis, there was a trend towards
      prolonged survival of female patients, patients with ICP symptoms and the
      surgical group. Data from different centers are essential to establish the best
      management of CM.

PMID- 15476075
TI  - TLIF--transforaminal lumbar interbody fusion.
AB  - Transforaminal lumbar interbody fusion (TLIF) is a relatively new technique of
      lumbar arthrodesis via posterior transforaminal approach to the disc, indicated
      mainly in cases of degenerative disc disease, low grade spondylolisthesis and
      reoperation for disc herniation, specially when there is indication for interbody
      fusion and posterior decompression. The main advantage of TLIF is that it allows
      the complete removal of the intervertebral disc through the vertebral foramen,
      decompression of the spinal canal and vertebral foramen with minimum risk of
      neural lesion, due to the access being lateral to the nerve roots. In this study,
      we describe the first 24 cases of TLIF that we have done, which shows to be very
      safe and efficient in our series, with an relief of pain in 83.3% of patients,
      great improvements in the life quality in 75% of cases and satisfaction with the
      surgery in 79.1% of patients.

PMID- 15476076
TI  - Surgical management of axis' traumatic spondylolisthesis (Hangman's fracture).
AB  - OBJECTIVE: To evaluate the results of surgical treatment using pedicle screws
      going through C2 pedicles for fixating the spondylolisthesis of the axis in
      patients who presented pseudoarthrosis after clinical treatment, or who have no
      condition for fixation with "halo vest", due to serious head trauma. METHOD: Ten
      patients have been operated from June 1998 to April 2002, nine suffering from
      traumatic spondylolisthesis of the axis caused by car accident and one horse
      fall. Four of those patients have undergone clinical treatment and presented
      signs of pseudoarthrosis, suffering intense pain at the movement of the cervical
      spine. Two of them presented moderate head trauma with multiple fractures of the
      skull. Another one was submitted to a surgical treatment for an acute extradural
      hematoma. Three patients presented a serious dislocation of C2 over C3. The
      patients were submitted to arthrodesis of the fractures with two screws, placed
      on the C2 pedicles, which allowed a better approximation of the fractures with
      the alignment of C2-C3. Two other patients required additional fixation with a
      plate on the lateral masses of C3. RESULTS: Nine patients had a good post surgery
      evolution with satisfactory consolidation of the fractures and disappearance of
      the symptoms. One patient had a good evolution but still has cervical pain
      resulting from strain. CONCLUSION: The fixation of the traumatic
      spondylolisthesis of the axis using screws in C2 pedicles and through fractures
      traces is a good option for treating patients who present pseudoarthrosis after
      clinical treatment or who present contraindication to the "halo vest", such as
      skull fracture or great lacerations in the scalp.

PMID- 15476077
TI  - Surgical management of cerebrospinal fluid rhinorrhea under endoscopic control.
AB  - The surgical management of cerebrospinal fluid (CSF) rhinorrhea has changed after
      the introduction of functional endoscopic sinus surgery.The following three cases
      illustrate the repair of CSF leaks with the use of rigid endoscope. Two patients
      had the diagnosis and the site confirmed after intrathecal fluoresceine saline
      injection. The obliteration of the CSF was achieved with fat free,
      mucoperichondrial or mucoperiostal free grafts taken from middle or inferior
      turbinate and kept in place by fibrin glue. Primary closure was achieved in all
      patients. The repair of the CSF rhinorrhea by endonasal endoscopic surgery is
      safe, effective and is a valid alternative to the cranial approach.

PMID- 15476078
TI  - Remote hemorrhage from the site of craniotomy.
AB  - Postoperative intracranial hemorrhage is a serious and sometimes a fatal
      neurosurgical complication. Hemorrhage occurring at regions remote from the site
      of intracranial operations comprises an uncommon affection, most ignored by the
      assistant physicians. It bares a still incomprehensive pathophysiology, despite
      several theories trying to explain it. Looks like a common sense that the
      presence of the remote site hemorrhage cannot be related to concomitant presence
      of hypertension, coagulopathy or undiscovered lesions. We report three cases of
      postoperative hemorrhages occurring in a remote site of supratentorial
      craniotomies, two patients presented cavernous sinus meningeoma and one patient
      was submitted to intracranial vascular surgery.

PMID- 15476079
TI  - Structural and microvascular study of soleous muscle of Wistar rats after section
      of the sciatic nerve.
AB  - It is not well established yet the relationship between the activation of
      satellite cells and skeletal muscle microcirculation after surgical denervation.
      Trough scanning and transmission electron microscopy methods, we studied
      comparatively the alterations of the soleus muscle in Wistar rats after surgical
      denervation. Our results evidenced the activation, duplication and migration of
      satellite cells to the interior of muscle fibers coexisting with a raise in the
      capillary density characterized by a higher number of anastomosis and capillary
      sprouts. We conclude that the microcirculation plays a key role in the
      regenerative process.

PMID- 15476080
TI  - [Pudendo-anal reflex in normal women].
AB  - The pudendo-anal reflex was studied in a sample of 31 normal women. Responses
      were obtained after bilateral independent stimulation of the clitoris, with
      surface recordings from both sides of the external anal sphincter. Responses were
      elicited with double-pulses of 0.2 ms duration with a interstimulus interval of 5
      ms, frequency of stimulation was lower than 0.5 Hz. A minimal of four responses
      were recorded after supramaximal stimulation. In one volunteer no response was
      recorded after unilateral stimulation. Latencies of the responses from the right
      and left sides of the anal sfincter after right and left stimulation were 36.35+/
      6.37, 36.28+/-6.23, 35.88+/-4.68, 36.44+/-4.45 ms, respectively. No relation was
      detected between latencies and age, body mass index and parity (considering
      either total parity or vaginal delivery only). In 12% of the recordings
      uncertainty was introduced in the latency measurements related to a poor signal
      noise ratio.

PMID- 15476081
TI  - [Study of the main risk factors frequencies for ischemic cerebrovascular disease
      in elderly patients].
AB  - Two hundred and sixty two patients with clinical diagnosis of permanent ischemic
      stroke, all of them aged 60 or more were retrospectively studied from the 1015
      cerebrovascular diseases (CVD) records of the Atherosclerosis League of the
      Neurology Clinics of the ISCMSP, from 1990 to 2002. The study emphasized
      modifiable risk factors frequencies for ischemic stroke in this population,
      considering gender and age of the patients. Results have evidenced that systemic
      arterial hypertension is a main risk factor significantly frequent in old people
      (87.8%), independently of gender and age. Smoking (46.9%) and alcohol consumption
      (35.1%) have revealed to be very frequent important modifiable risk factors
      especially among men. Lower frequencies have been presented for cardiac diseases
      (27.0%), Diabetes Mellitus (19.9%), and dyslipidemia (15.6%) as risk factors for
      ischemic stroke in old people of both genders and all ages after 60. There was
      relatively low frequency of hyperuricemia in this set of patients.

PMID- 15476082
TI  - [Cognitive function evaluation in school-age children from economically
      impoverished community: results of enriched education program].
AB  - Sixty-three school-age children of low socioeconomic status and exposed to
      adverse environmental factors (malnutrition, familiar distress and low familiar
      incomes) were submitted to neuropsychological tests to investigate possible
      cognitive impairments. Classical neuropsychological test battery was employed
      (Raven test, Bender Gestalt copy of complex figures, draw-a-man Goodenough test).
      Low intellectual level was found on 30% and 74% showed higher cognitive disorders
      (visuoperceptual skills and/or perseverations and/or global shapes perception
      and/or draw-a-man disturbances). These children attended to a school with semi
      boarding regimen which receives children under personnel and social adverse
      factors. School program was enriched with learning activity program based on
      Piaget and psychomotor exercises based on Lambert for at least one year. They
      also had some other activities, as painting, singing, computer training, English
      and Spanish classes. Twenty children were newly accepted and 43 attended at
      school for one, two or three years. We found significant correlations (p < or
      =0.05) between superior intellectual performances, bigger periods of attendance
      at school and methods for cognitive development. There was no association between
      other brain cognitive functions examined, the attendance to the teaching programs
      and the years of permanence at school.

PMID- 15476083
TI  - [Dermatoglyphics and body composition in obstructive sleep apnea].
AB  - Obesity is the main risk factor for obstructive sleep apnea syndrome (OSAS) and
      genetic patterns can modulate the pathogenesis of the disease. The aim of this
      study is to describe the anthropometrics and dermatoglyphics features among OSAS
      carriers. We collected information on Body Mass Index (BMI), Conicity Index (CI),
      Body Fat Mass (BFM), somatotype and fingerprints. Thirty-one cases of OSAS were
      compared to an equal number of controls. Membership to the obese category is
      based on observed BMI and BFM. The CI distribution among cases shows a strong
      central obesity component. The endomorph-mesomorph somatotype category
      predominates among cases showing high adiposity and relative muscle-skeletic
      development, such as relative linearity of great mass per unit of height.
      Increased morbidity, as given by more serious indices of apnea, correlates
      positively with higher mesomorphic predominance in the body composition. Analysis
      of dermatoglyphic data does not show significant statistical differences between
      OSAS--patients and controls.

PMID- 15476084
TI  - [Prototyping as an alternative to cranioplasty using methylmethacrylate:
      technical note].
AB  - The prototyping is a method for reconstruction of human body segments by computer
      software. It has been used in neurosurgery for cranial reproduction in patients
      allowing the programming of surgical procedures and the production of prosthesis
      to reconstruct bone failures in the skull. We present two cases of cranioplasty
      performed with the use of acrylic prosthesis constructed by prototyping. After 10
      months of follow-up, they do not present signs of infection and show good
      aesthetic result. The advantages pointed at the literature for this method
      (reduction of surgical time, easy technical handle, and good aesthetic result)
      were confirmed.

PMID- 15476085
TI  - Long term follow-up in a patient with papillary glioneuronal tumor.
AB  - We report a case of a young female patient with a rare and recently described
      form of brain tumor. This patient had a history of headache, hemiparesis and
      motor simple partial seizures. Her investigation revealed a brain tumor involving
      the left frontal and parietal lobes. The radiological images showed a cystic mass
      with multiple nodular masses and a rim of contrast enhancement extending from the
      right parietal cortex to the ipsilateral ventricle and corpus callosum. The
      patient underwent gross resection of the lesion and the histological analysis of
      the surgical specimen revealed a pseudopapillary structure formed by delicate
      vessels intermixed with a fibrillary pattern and bordered by intense astrocytic
      reaction with Rosenthal fibers. These features correspond to the recently
      described mixed neuronal-glial neoplasm, the papillary glioneuronal tumor. The
      patient has been followed for five years since the surgical treatment, without
      evidence of tumor recurrence, confirming the indolent behavior of this type of
      tumor.

PMID- 15476086
TI  - Blindness and total ophthalmoplegia after aesthetic polymethylmethacrylate
      injection: case report.
AB  - Microspheres of polymethyl-methacrylate (PMMA) are exciting new soft-tissue
      fillers that are becoming increasing popular for facial rejuvenation. Some
      reports of side effects of this procedure are basically in respect to dermal
      reaction, with late-onset granulomatous lesion with giant cells and vacuoles. We
      report blindness and total ophthalmoplegia after PMMA injection into glabellar
      area in a healthy woman and review the literature.

PMID- 15476087
TI  - Management of primary spinal chondrosarcoma: report of two cases causing cord
      compression.
AB  - Chondrosarcomas are malignant tumors that rarely grow inside the spinal canal.
      Prognosis depends on histological features, patient's age and surgical margins
      free from tumor. Response to radio and chemotherapy is poor. Ideal treatment
      consists of total "en-block" resection, not always achievable due to limitation
      of location, compromise of stability and risk of inducing neurological deficits.
      Two cases of spinal chondrosarcoma causing cord compression are reported, located
      in the cervical and thoracic spine. Microsurgical technique consisted of initial
      debulking followed by removal of margins until limits free from tumor were
      obtained. Total resection was accomplished and neurological function improved in
      both cases. Follow-up has been seven and one year respectively, with no evidence
      of recurrence and preserved neurological functions. Association between
      chondrosarcoma and estrogen-dependent tumor has been confirmed in this report.
      Although "en-block" resection of a chondrosarcoma should be tried whenever
      possible, tumor fragmentation should be considered in difficult cases, as in the
      present report, in which a long period free from recurrence with good quality of
      life can be obtained.

PMID- 15476088
TI  - Paraplegia complicating percutaneous vertebroplasty for osteoporotic vertebral
      fracture: case report.
AB  - We report a case of spinal cord and root compression during percutaneous
      transpedicular polymethylmethacrylate vertebroplasty (PTPV) for a compression
      fracture due to osteoporosis. Sudden onset of excruciating pain in the
      distribution of the right sixth intercostal nerve with hyperemia along its path,
      prompted the interruption of the procedure. Under narcotic sedation the patient
      was taken to the ICU and 10mg of dexamethasone was administered intravenously.
      Few hours later she developed paraplegia with preservation of light touch and a
      CT scan and MRI showed epidural extravasation of polymethylmethacrylate with
      spinal cord and root compression. Surgical decompression was followed by
      neurological recovery. The cement could be removed after been thinned out by high
      speed drill, with microsurgical technique, through a wide three level laminectomy
      of D5 to D7. Extravasation of cement is commonly encountered in PTPV and most of
      the time it is asymptomatic. Root compression may require surgical intervention
      if nonresponsive to steroid treatment. Cord compression is less often seen and
      requires emergency surgery. The cement does not adhere to the duramater and it
      can be removed easily.

PMID- 15476089
TI  - Laceration of the posterior inferior cerebellar artery by suboccipital puncture
      of the cisterna magna: case report.
AB  - We report the case of a 27 year old man who presented to the emergency room of a
      hospital with headache, vomiting and an episode of loss of conciousness. A
      cranial CT scan was normal and the patient discharged. Ten hours later he came to
      the emergency room of our hospital with the same complaints. A technically
      difficult cisternal puncture in an anxious patient who moved during the needle
      introduction was done. The CSF sample showed 1600 intact red blood cells without
      other alterations. His headache worsened and after 6 hours he became drowsy, numb
      and exhibited decerebration signs. A new CT scan showed diffuse subarachnoid and
      intraventricular blood. An emergency angiogram demonstrated laceration of a left
      posterior-inferior cerebellar artery in its retrobulbar loop with a
      pseudoaneurysm. He was successfully treated by surgical clipping without injury.
      Sixteen days later he was discharged with a normal neurological exam.

PMID- 15476090
TI  - Syringohydromyelia associated to therapeutic procedures for severe forms of
      neurocysticercoses: case report.
AB  - Syringohydromyelia is defined as a longitudinal dilatation of the central canal
      of the spinal cord with accumulated cerebrospinal fluid. This condition may cause
      neurologic deficits when the cavity enlarges and compresses the spinal cord. We
      present the case of a 33 years-old female with progressive paraparesis caused by
      syringohydromyelia. This patient underwent previously multiple clinical and
      surgical treatments for severe form of neurocysticercosis. Surgical decompression
      of the posterior fossa and syringostomy resolved the neurologic symptoms. The
      possibility of syringohydromyelia should be considered in the case of patients
      who have previously undergone surgical and clinical treatment for severe form of
      neurocysticercosis.

PMID- 15476091
TI  - Hemorrhagic stroke after naphazoline exposition: case report.
AB  - Ten percent of all strokes are due to spontaneous cerebral hemorrhages. They are
      associated to drugs (licit and illicit) in 9.5% of all cases in young adults.
      This is a case report of a 44-year-old man, without previous morbidities, who
      presented a sudden onset headache and arterial hypertension 24 hours after use of
      naphazoline as nasal decongestant. Cranial tomography showed right thalamus
      hemorrhage. Cerebral angiography showed no aneurisms, vascular malformations or
      vasculitis. No other risk factors were found during investigation in this patient
      and the stroke was attributed to naphazoline exposition.

PMID- 15476092
TI  - Interferon beta-1a in chronic inflammatory demyelinating polyneuropathy: case
      report.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune
      mediated neuropathy. It presents with a course of progression which may be slow
      and steady or step-wise or relapsing. Sensory ataxic polyneuropathy may be the
      only clinical manifestation of this disease. Treatment with interferon beta1a
      (INF beta1a) has been tried with different results in patients who were
      refractory to other, more conventional, immunomodulatory therapies. Here we
      report on a patient who had a relapsing form of pure sensory ataxic CIDP and who
      failed to respond to intravenous human immunoglobulin. He was put on INF beta1a
      for 3 years. During this period he suffered no relapses while his condition
      stabilized.

PMID- 15476093
TI  - SEP-diagnosed neuropathy of the lateral cutaneous branch of the iliohypogastric
      nerve: case report.
AB  - The article pertains to the uncommon clinical case of a patient with a proximal
      neuropathy of the lower extremity. It outlines the electrophysiological
      evaluation and reviews the medical literature. The electrophysiologic test that
      most accurately revealed the neuropathy was the segmental somatosensory evoked
      potential (SEP) of the lateral cutaneous branch of the iliohypogastric nerve. It
      showed well-defined and replicable cortical waveforms following the excitation of
      the lateral cutaneous branch of the iliohypogastric nerve in the asymptomatic
      lower extremity, but failed to present somatosensory evoked potentials arising
      from the excitation of the contralateral nerve in the symptomatic lower
      extremity. We did not find any previous reports diagnosing that particular
      pathology by the use of segmental SEP. In conclusion, it is important to remember
      that the accurate diagnosis of patients complaining of pain and dysesthesia in
      the proximal part of the lower extremities can possibly be achieved through the
      use of electrophysiologic tests such as the segmental SEP.

PMID- 15476094
TI  - Progressive cervicocranial arteriopathy with dilatations and stenoses: case
      report.
AB  - We report the case of a 36 year-old woman who presented occlusion of a basilar
      artery fusiform aneurysm (FA) associated with pontine infarction, and two
      episodes of subarachnoid hemorrhage possibly due to arterial dissection. She also
      had asymptomatic FAs in the right middle cerebral and left internal carotid
      arteries. Over 5 years, lesions suggestive of fibromuscular dysplasia in the
      right vertebral artery and occlusion of the left vertebral artery were observed.
      This combination of lesions emphasizes the possibility of a common pathogenetic
      mechanism causing different degrees of media disruption in cervicocranial
      arteries.

PMID- 15476095
TI  - [Nummular headache: case report].
AB  - Nummular headache or coin shaped cephalalgia was first described by Pareja and
      coworkers in 2002. It seems to be a primary headache that has a chronic course,
      with a circumscribed area of pain described by the patients as elliptic or coin
      shaped. Patients experience periods without pain followed by bouts of daily
      headache. In the original series of thirteen cases it was sometimes associated
      with other primary headaches, but not necessarily. It could also be related to
      cranial trauma. We present the first case of of nummular headache described in
      our country with clinical features similar to the original series. We intend to
      alert neurologists and pain specialists to the existence of this unusual headache
      and also discuss the possible differential diagnosis of this cephalalgia.

PMID- 15476096
TI  - [Worster-Drought syndrome: case report and distinction in relation to Foix
      Chavany-Marie syndrome].
AB  - Worster-Drought syndrome is a clinical entity resulting from cortico-nuclear
      tract or cerebral cortex injury, without defined etiology, characterized by
      alteration of the muscles that control the lips, jaw, tongue, soft palate and
      pharynx. The main clinical manifestations are alterations in the fonation and
      deglutition. We describe the case of a 15 year old female patient, displaying the
      cited syndrome. The clinical, radiological and neurophysiological findings are
      compared with the described data in the literature. We question the connection
      between Worster-Drought and Foix-Chavany-Marie syndromes, as well as the possible
      relationship with use of abortive drugs and similar oromotor problems as found in
      these two syndromes.

PMID- 15476097
TI  - [Language evaluation in children with bilateral cerebrovascular disease: study of
      two cases].
AB  - We describe two children, aging 5 years and 6 months and 5 years and 10 months
      respectively, when the phonoaudiological assessment was conducted. Both children
      presented bilateral cerebrovascular disease (CVD), confirmed in the acute phase
      by means of clinical and image neurological test. During this phase, the two
      patients were examined by a pediatric neurologist of the Pediatric Neurology
      Discipline of FCM/UNICAMP, pediatric CVD ambulatory. Audiologic Assessment,
      Protocol for Infant Language Assessment, and Peabody Picture Vocabulary Test were
      used in the evaluations. The qualitative analysis of the two subjects from a
      phonoaudiological and neurological point of view has shown the recovery of
      adquired language disturbance with no influence whatsoever in the development of
      the first subject and subtle language and/or learning process alterations for the
      second subject. The cases study has revealed that the predominant aspects should
      be analyzed in an individual, quantitative, and qualitative basis to lead to
      conclusive findings.

PMID- 15476104
TI  - [Orphan diseases -- a global problem].

PMID- 15476105
TI  - [CPAP: effect on lung elasticity?].

PMID- 15476106
TI  - [Does nCPAP-therapy change the lung function of patients with obstructive sleep
      apnea syndrome?].
AB  - BACKGROUND: nCPAP-therapy is standard for patients with obstructive sleep apnea
      syndrome (OSAS). This study investigated, if nCPAP changed the patients lung
      function. PATIENTS AND METHODS: Lung function of 228 OSAS patients without co
      prevalent lung disease, who received nCPAP for the first time, was examined
      (whole body plethysmography, spirometry, and blood gas analysis). After 1, 2, and
      3 years the results of the re-examined patients were compared with their
      individual starting results. RESULTS: The results of the patients in the basic
      and in the follow-up examinations was within standard range. During
      reexamination, an improvement of inspiratory vital capacity was registered
      repetitively, especially in smokers. On the other hand, MEF 50 decreased within
      the first two years and FEV (1) %VC, but not FEV (1), decreased after 2 and 3
      years of reexamination. CONCLUSIONS: Neither obstructive nor restrictive lung
      diseases were diagnosed under nCPAP-therapy within three years. This study with a
      retrospective design showed significant improvements of vital capacity (VC) in
      patients with OSAS, especially in smokers, under nCPAP-therapy. This increase can
      be explained by an effect of practice in the examination and by recruitment of
      formerly hypoventilated lung areas. As MEF 50 and FEV (1) %VC depend on VC, the
      decrease of both parameters may be caused by the increase of VC. In summary,
      nCPAP did not cause negative effects of lung function in the investigated
      patients over a period of 3 years.

PMID- 15476107
TI  - [Bronchological bioptic diagnosis of lung cancer -- cytology and/or histology?].
AB  - INTRODUCTION: Bronchial carcinomas are commonly diagnosed through histological
      analysis of forceps biopsies. The use of flexible bronchoscopic biopsy techniques
      has led to an increase in the number of cytological investigations. The present
      study has the aim to assess the diagnostic efficiency of histology, cytology and
      their combined use. METHOD: In a retrospective analysis, 3630 cytological and/or
      histological samples that had been obtained bronchoscopically between 1/97 and
      12/03 prior to surgery in 1436 patients, who were operated due to bronchial
      carcinoma, were compared to corresponding histological findings in the resected
      material. RESULTS: In 1888 preoperatively analysed areas the resected material
      ultimately allowed the detection of malignant lesions. Among these cases,
      histologic analysis of forceps biopsies yielded 399, cytological analysis 728,
      and their combined use 801 correct diagnoses prior to surgery. The combination of
      both procedures led to an increase of sensitivity by 16 % and 13.0 % compared to
      histology and cytology, respectively, as separate procedures. Histologically
      there were 149 cases, cytologically 1061 cases, and in combination 1040 cases
      that were falsely diagnosed as negative prior to surgery. The use of histology
      and/or cytology allowed to correctly detect 1250 areas of the resected material
      as free of malignant lesions. Specificity was 99.8 % for both methods.
      CONCLUSION: Currently bronchial carcinomas are often diagnosed preoperatively by
      minimally invasive cytological procedures. The present results demonstrate
      cytology and histology to be procedures that are complementary to each other.
      Their combined use offered the greatest diagnostic yield and therefore should be
      considered standard in the diagnosis of bronchial carcinoma.

PMID- 15476108
TI  - [Patient with left-sided pleural effusion and large structures of soft-tissue
      density in the mediastinum].
AB  - A patient was admitted to the hospital to clarifying a left-sided pleural
      effusion. Typical cytological findings in pleural effusion did not leave a doubt
      about being present a pancreatitis in conformity with clearly increased levels of
      lipase and amylase in the effusion fluid. The CT of the upper abdomen showed
      signs of a exsudative pancreatitis. In the chest CT as well as in transesophageal
      ultrasound evaluation large structures of soft-tissue-density together with areas
      of encapsulated fluid were seen in the dorsal mediastinum reaching down to the
      diaphragm and abdomen. Just with subsequent diet and strict termination of any
      alcohol consumption the pathological findings recovered completely. Due to the
      expansive involvement of the pleural, mediastinal and abdominal compartments this
      is an extraordinary case of acute pancreatitis.

PMID- 15476109
TI  - [Clinical pathway for the evaluation of dyspnea in outpatients pulmonary care].

PMID- 15476110
TI  - [Manual for the application of hyperventilation testing in outpatient pulmonary
      care].

PMID- 15476112
TI  - [Clinical presentation, diagnosis and treatment of Mycoplasma pneumoniae
      pneumonia].
AB  - Mycoplasma pneumoniae is a common respiratory pathogen in community acquired
      pneumonia. In severe cases extrapulmonary manifestations of the disease may be
      prominent. Proof of infection is found, though usually delayed, through serologic
      methods. A calculated therapy of community acquired pneumonia, especially in
      younger patients with interstitial infiltrates, should therefore include
      effective treatment for Mycoplasma pneumoniae. Macrolide antibiotics are the most
      commonly used antibiotics in the treatment of mycoplasma infection, alternatives
      include ketolides, quinolones and tetracyclines.

PMID- 15476113
TI  - [Spiroergometry in patients with pulmonary hypertension by lung fibrosis, primary
      pulmonary hypertension, chronic thrombolic pulmonary hypertension and cystic
      fibrosis].

PMID- 15476114
TI  - [Impact of bronchial-artery-revascularization on the early reperfusion period in
      canine lung transplantation].

PMID- 15476115
TI  - [Robert Loddenkemper on the occassion of his 65th birthday].

PMID- 15476116
TI  - [Influences of the structural-dynamic approach on contemporary psychopathology].

PMID- 15476117
TI  - [Structural dynamics and vulnerability models].
AB  - This paper links Janzarik's structural-dynamic coherence model with Zubin and
      Springs' vulnerability model and shows that Janzarik's model enables reduction of
      the multiple and partially speculative single factors of the vulnerability model
      to a functionally interpretable and coherent theory. We will then review the
      internal logic of the structural-dynamic coherence model concerning the
      explanatory power of pathogenetic models of schizophrenia and show that Janzarik
      is confirmed by the literature in the assumption that primary hypodynamism is
      present in the run-up to the schizophrenic prodrome and first manifestations.
      Structural dynamic derailment as a core phenomenon in psychotic disorders is also
      accepted and confirmed by the literature. On the other hand, the
      'einheitspsychose', or unitary psychosis, basis of the structural dynamic model
      is controversial. In this context the author discusses his own Vienna school's
      Axes model, which suggests a variety of further determinants of the pathoplastic
      formation of the idiopathic psychosyndrome above and beyond Janzarik's model.
      Finally we discuss further questions which may arise out of the structural
      dynamic model.

PMID- 15476118
TI  - [Idiopathic psychosyndromes in the sight of Werner Janzarik].
AB  - In the 50 years of his scientific activity Werner Janzarik has also dealt with
      idiopathic psychosyndromes, the affective and schizophrenic psychoses. Our paper
      shows that the scientific work of Janzarik has essentially participated in the
      foundation of a scientific psychopathology of idiopathic psychosyndromes. In this
      connection Janzarik has used the whole spectrum of methods relevant for
      psychiatry in a very fruitful manner. It becomes evident that the step by step
      developed structural-dynamic concept of an anthropologically psychopathology
      represents today a substantial basis of a scientific psychiatry that presupposes
      understanding and knowledge of a comprehensive psychiatric experience related to
      patients. The transfer of his structural-dynamic approach to the idiopathic
      psychosyndromes turns out to be a new way of synopsis and integrated
      interpretation of the psychopathological and biological data relevant for
      psychiatry. His conclusive psychopathological concept certainly has,
      independently of its importance for psychiatric practice, a value on its own but
      must not dispense with psychiatric practice. The structural-dynamic design of
      Janzarik enables as scarcely an other concept manifold concretisations and
      transformations into empirically verifiable working hypotheses, also in the
      utilisation for the clinical psychiatry of idiopathic psychosyndromes and in
      reflecting their diagnostic and therapeutic aspects. The newly again recognisable
      tendency to a dividing up of our discipline into a somatic and a psychic
      position, into too much reductionistic and objectifying procedures of a
      biological psychiatry and one-sided psychonomic, anthropological, psychoanalytic
      and system-theoretical interpretations, proves the necessity and fruitfulness of
      the approach of Janzarik and its untimely character in a positive sense of great
      promise for the future, demonstrated just also in idiopathic psychosyndromes. The
      structural-dynamic way of consideration of idiopathic psychosyndromes, on the
      first sight, faced with the scientistic orientation of the contemporary
      psychiatry, appearing not useful, has meanwhile long ago on a large scale arrived
      at the research and practice of clinical psychiatry of affective and
      schizophrenic psychosyndromes.

PMID- 15476119
TI  - [Neuropsychological equivalences and therapeutic consequences of the dynamic
      structural model].
AB  - Firstly the core concepts of the dynamic structural model and the methods from
      which the model was developed will be discussed. These core concepts include
      concepts of personality structure and affect dynamic, of dynamic affective
      derailment with dissociation of individual element structures, the capacity of
      disactualisation of unwanted mental content, and autopraxis as the basis of
      memory renewals, which are formed and channelled through selection. Furthermore
      we will consider the dependence of memory function on texturing, development of
      coherence, affective freighting and repetition of usage in Janzarik's system.
      Neuropsychological counterparts are to be found in experimental studies on
      filter, gating and control functions, in studies on automatic vs. controlled
      processes, the central executive and executive control function. Autopraxis and
      priming operations will be related to each other. Furthermore, the connection of
      neuronal plasticity to a raised signal-to-noise ratio and the relationship to
      extinction of delusional content through broadening of new fields of experience
      will be discussed. In a summary of the frappant parallels of experimental and
      clinical viewpoints of Janzarik's model we will show the therapeutic perspective
      and the psychotherapeutically important integration of the lifeworld of the
      patient with experimentally investigated neuropsychological functions through
      Janzarik's conceptualisation.

PMID- 15476120
TI  - [Psychopathology of development and structural dynamics].
AB  - The mental structure provides every human with a potential repertoire of
      behavior. In every interaction a reactivation of past actualization- and
      representation processes concerning the particular prevailing context takes
      place. A child's mental structure should not be devaluated in comparison to a
      structure of an adult person. Levels of functioning depend on the developmental
      age. Structural dispositions consist of represented experiences of interaction.
      The so-called affect attenuement plays an important part in individual affect
      regulation. If the structural representation follows mechanisms of memory,
      procedural structural dispositions may be postulated, which affect the behavior
      besides iconic and symbolic representations. Within the structure affect
      dispositions are integrated. They are able to give value to certain contents of
      experience and reexperience. Disorders in the development of empathy are
      connected with impairments of the structural development. By inherent faintness
      of the regulation of affects or by sensitization and traumatization processes,
      which involve dissociative phenomena, the affective load of representations can
      be changed. This may result in structural deficits.

PMID- 15476121
TI  - [Structural dynamics and psychoanalysis -- plea for a dialogue].
AB  - The present paper argues in favour of a dialogue between the structural dynamics
      and psychodynamics. This dialogue has not really taken place, but it would yield
      important benefits for both sides. First of all, like any other psychiatric
      discipline psychoanalysis needs a psychopathology as a basic science in order to
      find its proper place within the psychiatric field; this basic theory is granted
      by the structural dynamic approach. Both theories encompass many areas of
      clinical practice and psychological-psychiatric theory. It is worthwhile to try
      to translate the main concepts of the one approach into the other's terminology.
      Thus, specific advantages and specific shortcomings in each theory can be
      unveiled. Three examples are presented, the concept of the unconscious,
      representational theories and the concept of desactualisation. As an example of
      how psychoanalysis could profit from structural dynamics, the integration of
      neurobiological basis into a psychological concept is mentioned. The structural
      dynamic psychopathology may likewise profit from psychoanalysis, mainly in terms
      of its therapeutic application.

PMID- 15476122
TI  - [The importance of the phenomenom "imagination" in the scientific work of Werner
      Janzarik].
AB  - This paper in three parts and conclusion begins with the description of
      Janzarik's progression of thought, which originates in the narrowing of the gap
      between Jasper's descriptive phenomenology and anthropological phenomenology with
      its interpretive elements. Janzarik's structural-dynamic psychopathological
      approach has grown and differentiated from originally relatively narrow
      psychopathological questions to become an anthropology which aims to describe
      human assumptions concerning individual development/growth. The experience
      dimension is the focus, without suppressing interdisciplinary, objective
      findings, such as the inclusion of ethology. The mere clinical reconstruction of
      mental processes with all its heuristic risk was characterised by Janzarik as
      'pure psychopathology'. In the section concerning structure and representation
      and their dependence on affect dynamic, we will emphasise the procedural nature
      of Janzarik's anthropology regarding developmental processes and its relationship
      to the philosopher Plessner's work in philosophy. The significance of the
      imagination in Janzarik's work contrasts to other philosophers who regard the
      imagination as ontological weakness, a deficiency, non-real, Janzarik, like Kant,
      sees the imagination as a constituent of reality. This will be exemplified in the
      characterisation of the mental field concerning the structural-dynamic model, the
      psychopathology of delusion as well as the oneiroid psychopathology. Finally the
      connection between autopraxis, Janzarik's core concept for the spontaneity of
      incidences and memory functions, and imagination will be described, which to a
      certain extent emphasises the working character of imagination for the flow of
      controlled mental activity. We will finish with the observation that Janzarik's
      work especially stresses experience and thus also the patient's individuality.

PMID- 15476125
TI  - Factors that affect satisfaction with neonatal-perinatal fellowship training.
AB  - This study was designed to assess neonatal fellows' satisfaction with their
      training and the role of mentorship. A 31-question survey was sent to all second-
      and third-year fellows in the United States and Canada (n = 304). Responses were
      received from 201 fellows (66% response rate). Respondents were evenly
      distributed between second- and third-year fellows. Overall, 75% were satisfied
      with their training. Eighty percent had a mentor on the neonatal faculty. Only
      2.5% believed that they would not fulfill the sub-board research requirement, but
      another 24% were unsure of completion. The presence of a mentor correlated with
      being prepared for academic practice (p = 0.013) and plans to enter academic
      practice (p = 0.031). Correlation between mentorship and completion of the
      research requirement showed a trend (p = 0.09). Twenty-five percent of neonatal
      fellows are not satisfied with their training and believed that they may not
      complete their research requirement. Fellows who had a mentor were more prepared
      for academic practice and were more likely to be satisfied with their fellowship
      training. Mentorship is important in neonatal training programs.

PMID- 15476123
TI  - [Structural dynamics and delinquent behavior].
AB  - Using key concepts of Janzarik's structural-dynamic model, this article describes
      some of the potential uses of this model in a forensic setting. We will
      especially take into account that aspect of Janzarik's work from the start of his
      research in the 1950s through to the late 1990s which particularly addressed
      forensic questions. Using the example of dynamic Unstetigkeit and structural
      derailment, the aspect of 'mental content becoming autonomous' will be considered
      regarding Schuldunfahigkeit. Taking the example of autopraxis, successful and
      disturbed balance between impulsivity and self-control in personality disorder
      will be clarified and concerning the concept of self-corruption the self-induced
      corroboration of dissocial attitudes will be explained. The author considers the
      user-friendly work of Janzarik to be a fundamental instrument for answering
      questions in forensic psychiatry.

PMID- 15476126
TI  - Congenital lipoblastoma of the scalp.
AB  - Lipoblastoma is a unique tumor of infancy and early childhood that can occur
      congenitally. It commonly occurs in trunk and extremities, but also rarely in
      head and neck. We have not encountered any report of congenital lipoblastoma of
      scalp in published literature. Here we describe the case of an infant who
      presented with a rapidly growing large scalp mass that measured 15 x 15 x 10 cm.
      At birth, the mass was located on the bregma but progressed to extend into the
      left upper eyelid and eyebrow. The mass was resected in two stages: the first
      stage consisted of resecting the scalp mass and the second stage consisted of
      excising the eyelid extension of the lesion. The histology of both resection
      specimens was similar and showed lobular adipose tissue separated by fibrous
      septae, which was consistent with a lipoblastoma. The child is free of recurrence
      at follow-up 3 years after the resection.

PMID- 15476127
TI  - Differential clinical manifestations of congenital cytomegalovirus infection
      between dizygotic twins: a case report.
AB  - To understand a mechanism for the difference in clinical manifestations of
      congenital cytomegalovirus (CMV) infection between dizygotic twins, the placentas
      of the dizygotic twins were evaluated for the number of the cells infected with
      CMV by immunohistochemical and in situ hybridization studies. A Japanese woman
      with dizygotic twin pregnancy had immunoglobulin M antibodies to CMV at 15 weeks
      gestation. Intrauterine growth retardation was noted only in the first twin. At
      birth, CMV was isolated from urine culture in both twins. Clinical manifestations
      for CMV, such as petechiae, jaundice, hepatosplenomegaly, and deafness were more
      pronounced in the first twin than in the second twin. Immunohistochemical and in
      situ hybridization studies showed CMV-positive cells two or three times more
      densely distributed in the placenta of the first twin compared with the second
      twin. These data suggest the severity of CMV manifestations of dizygotic twins
      may be in accord with the number of CMV-positive cells in the placenta.

PMID- 15476128
TI  - Incarceration of the retroverted uterus at term gestation.
AB  - Incarceration of the retroverted uterus is a rare complication of pregnancy and
      rarely persists until term. The diagnosis is extremely difficult to make and a
      cesarean section should be performed in such cases. A 33-year-old Japanese woman
      was admitted at 40 weeks gestation for evaluation of preeclampsia. Vaginal
      examination revealed that the uterine cervix could hardly be visualized, although
      the fetal head was impacted in the pelvis. These findings suggested incarceration
      of the retroverted uterus. Magnetic resonance imaging (MRI) was performed and
      clarified the exact anatomical relationship and confirmed the diagnosis. She
      therefore underwent a cesarean section and a male infant weighing 3552 g was
      delivered with Apgar scores of 9 and 10 at 1 and 5 minutes, respectively. At
      surgery she was found to have an adhesion between the uterus and the pouch of
      Douglas. MRI is a useful tool in correctly making the diagnosis of uterine
      incarceration and facilitates preparation for a cesarean section.

PMID- 15476129
TI  - The effect of positioning on energy expenditure in preterm infants: a feasibility
      study.
AB  - The aim of this study was to determine the feasibility of a study of the effect
      of positioning on energy expenditure in preterm infants. We performed a
      prospective, randomized, clinical cross-over pilot study of eight healthy,
      appropriate weight for gestational age, gavage-fed, clinically stable preterm
      infants at the postmenstrual age of 30 weeks. Prior to the study and in accord
      with our feeding protocol, infants uniformly received either their own mother's
      milk or a preterm formula. Each infant was studied in four different positions
      after randomization to eight different sequences. Infants were studied asleep, 90
      minutes after feeding, after 20 minutes of being nursed in a given position. They
      were cared for in a servo-controlled convective incubator during the metabolic
      measurements, which were performed by indirect calorimetry. Energy expenditure
      was not significantly affected by the body position in which the infant was
      studied. The difference between the highest and the lowest mean energy
      expenditure was 3.7% of the highest one. We conclude that attempts to minimize
      energy expenditure by modifying infant positioning are likely to be
      insignificant, from a practical standpoint, because of the nonsignificant or
      minimal differences in energy expenditure.

PMID- 15476130
TI  - Rare manifestations of sirenomelia syndrome: a report of five cases.
AB  - Five cases of sirenomelia presented with rare manifestations are discussed. Three
      neonates were born alive and died within 2 to 12 hours after birth. One case was
      the offspring of a triple in vitro fertilization pregnancy with history of early
      intrauterine death of one of the triplets. The main features included fusion of
      lower extremities (five of five), renal agenesis (three of five), polycystic
      renal dysplasia (two of five), anal atresia with large bowel hypoplasia (three of
      five), pulmonary hypoplasia (four of five), and single umbilical artery (five of
      five). Other features that have only rarely been associated with sirenomelia
      included concurrence of congenital heart disease and neuroblastoma, gallbladder
      agenesis, and upper extremity defects.

PMID- 15476131
TI  - Low colony counts of asymptomatic group B streptococcus bacteriuria: a survey of
      practice patterns.
AB  - The purpose of this study was to survey expert opinion on the management of low
      colony counts (< 100,000 colony forming units/mL) of asymptomatic group B
      streptococcus (GBS) bacteriuria discovered in the first trimester. A survey was
      sent to the 241 senior obstetricians affiliated with each of the Obstetrics and
      Gynecology training programs in the United States on July 10, 2002. Surveys
      received by the deadline (September 1, 2002) were included in the dataset. Eighty
      five completed surveys were returned for a response rate of 35%. Seventy-seven
      percent reported treating low colony counts of asymptomatic GBS bacteriuria in
      the first trimester at the time of diagnosis, whereas 23% stated they did not
      treat prior to labor (margin of error 7.5% with 95% confidence). Nine percent
      stated that their institution had a written protocol for the treatment of low
      colony counts of asymptomatic GBS bacteriuria. Two physicians indicated that they
      screened for asymptomatic GBS bacteriuria at 28 weeks. Currently, no generally
      accepted protocol for the management of low colony counts of asymptomatic GBS
      bacteriuria exists. This survey indicates that most of the responding senior
      obstetricians at United States training programs treat low colony counts of
      asymptomatic GBS bacteriuria in the first trimester.

PMID- 15476132
TI  - Management of infiltration injury in neonates using duoderm hydroactive gel.
AB  - Neonates are at increased risk of injury from infiltration of intravenous fluids
      because of small vessel size and immature skin structure. Until recently,
      hyaluronidase injection was used to prevent tissue injury following the
      infiltration of intravenous solutions in neonates. The production of
      hyaluronidase injection was discontinued in 2001. The alternative, compounded
      hyaluronidase injection is not regulated by the U.S. Food and Drug Administration
      and is subject to variation in quality assurance practices. Amorphous hydrogels
      have been used as wound dressings for sloughy or necrotic wounds in a variety of
      clinical settings. Hydrogels facilitate autodebridement of the wound by
      rehydrating slough and enhancing the rate of autolysis. No adverse effects or
      increased infection rates have been associated with the use of hydrogel
      dressings. DuoDerm Hydroactive gel is a sterile, preservative-free, viscous,
      hydrating gel composed of natural hydrocolloids. We report our experience using
      DuoDerm Hydroactive gel for management of injury secondary to the infiltration of
      total parenteral nutrition solution and lipid emulsion in three neonates.

PMID- 15476134
TI  - Sudden and unexpected fetal death associated with agenesis of the arcuate nucleus
      in the medulla oblongata.
AB  - Abnormalities have been reported in the medullary arcuate nucleus (ARCN) in
      unexpected late fetal death. They speculated that this developmental anomaly may
      underlie cardioventilatory abnormalities intrapartum and postpartum. This article
      describes a case of an unexpected late fetal death associated with absence of the
      ARCN.

PMID- 15476133
TI  - Is 1-hour glucose screening test reliable after a short-term administration of
      antenatal betamethasone?
AB  - This study was designed to determine whether betamethasone has any effect on 1
      hour (50-g) glucose screening test in nongestational diabetic pregnancy, and if
      any exists, to determine if this effect is transient or permanent. If the effect
      is temporary, the study was designed to determine the duration of this glucose
      intolerance effect and to determine the timing of 1-hour glucose screening test
      after betamethasone usage. One hundred fourteen pregnant women with a diagnosis
      of preterm labor at 24 to 34 weeks gestation were enrolled into the prospective
      study. One-hour glucose screening test was performed before initiation of
      hydration treatment. Forty pregnant women with normal 1-hour glucose results, who
      also had responded to hydration therapy, made up our study group. Twenty-four
      hours, 72 hours, and 1 week after administration of betamethasone, 50-g glucose
      challenge tests were again performed. A 3-hour glucose tolerance test was
      performed in pregnant women, whose 1-hour screening test had been positive 1 week
      after corticosteroid administration. In the evaluation of data, one-way, variance
      analysis and Tukey's multiple comparison test were used. The mean value of 1-hour
      glucose results of 50-g challenge test at the 24 hours was significantly higher
      than the mean value of 1-hour glucose results of the test done initially before
      betamethasone administration and than those of the tests done at 72 hours and 1
      week (p < 0.001 for these three groups). There was no statistically significant
      difference between the mean values of 1-hour glucose results of the test done
      before betamethasone administration and both the results of the tests done at 72
      hours (p = 0.96) and 1 week (p = 0.99), separately. There was no significant
      difference between the mean 1-hour glucose results of the tests at 72 hours and 1
      week (p = 0.99). The test results were positive in 42.5%, 10%, and 5% of the
      patients, respectively at 24 hours, 72 hours, and 1 week. The betamethasone
      administration significantly deteriorates 1-hour glucose screening test results
      in the nongestational diabetic patients but this effect of betamethasone is
      transient. Because of its high false-positivity at 24 hours (42.5%) and at 72
      hours (10%) in women with initial negative 1-hour glucose screening test, we
      suggest that 1-hour glucose screening test in pregnant women be postponed at
      least 1 week after betamethasone administration or perform the test before
      administration of betamethasone.

PMID- 15476135
TI  - [Quality assurance after (section sign) 137 SGB V in otorhinolaryngology, quo
      vadis?].

PMID- 15476136
TI  - [Subtemporal approach according to house versus Wigand in intrameatal CPA tumors
      type A].
AB  - BACKGROUND: The subtemporal approach is indicated in intrameatal CPA tumors type
      A in order to preserve hearing. The exploration of the inner auditory canal for
      tumor exposure varies. It reaches from a locally limited uncovering of the bony
      inner auditory canal to a complete removal of the surrounding bony bed with the
      circular skeletization (360 degrees ) according to Wigand of the 7 (th) and 8
      (th) nerve. Concerning the preservation of the function of the cranial nerve as
      well as an avoidable hyperelevation of the temporal cerebral lobe with a possible
      consecutive organic brain syndrome, both approaches have often been discussed
      controversially. METHOD: In a quality assurance analysis, we examined patients
      suffering from a unilateral, intrameatally limited CPA tumor type A in tumor
      stages 1 to 5. The functions of the 7 (th) and 8 (th) cranial nerves were
      assessed according to the consensus conference "Systems for reporting results in
      acoustic neuroma", Tokyo, November 2001, under consideration of the
      recommendations of the "American Academy of Otolaryngology, Head and Neck Surgery
      -- Committee on hearing and equilibrium guidelines for the evaluation of hearing
      preservation in acoustic neuroma", 1995, as well as indications for a possible
      organic brain syndrome. The results then were compared to current literature.
      RESULTS: 37 patients with an intrameatal confined CPA tumor after subtemporal
      tumor exstirpation were evaluated. In these patients, the inner auditory canal
      was only exposed in the area of the bony tectum (90 degrees - 120 degrees )
      adjusted to the volume of the tumor, as described by House: 1 patient with tumor
      stage 1, 2 patients stage 2, 12 patients stage 3, 16 patients stage 4 and 6
      patients with a tumor stage 5. The N. VII was anatomically preserved in 100 %.
      Immediately after surgery the function of N. VII was assessed in 32 % of the
      cases as stage I, 43 % stage II, 3 % stage IIIa, 14 % stage IIIb, 3 % stage IV, 0
      % stage V, 5 % stage VI. All patients in stage VI had a restricted function of N.
      VII in stage II or IIIa already before surgery. N. VIII could be preserved
      anatomically in 78 % of the cases. 1 to 6 months postoperatively the hearing was
      at stage A in 10 % of the cases, at 25 % in stage B, 33 % in stage C, 16 % in
      stage D, 5 % in stage E and 11 % in stage F. One patient demonstrated signs of a
      possible organic brain syndrome postoperatively even after 12 months of latency
      (headache, unsteady walking, attention disorders). CONCLUSION: When comparing own
      data with the clinical results from literature, no differences can be found
      concerning the function of the 7 (th) and 8 (th) cranial nerves. There are no
      data concerning the incidence of a potential organic brain syndrome. The
      advantage of the House method is a noticeably reduced drilling time as well as
      possibly a reduced elevation of the temporal cerebral lobes. The Wigand method,
      however, allows a better overview and is needed for extrameatally growing tumors
      anyway.

PMID- 15476137
TI  - [Evaluation of an electrode design for the combined electric-acoustic
      stimulation].
AB  - BACKGROUND: The objective of this study was to assess the intracochlear position
      and the extent of trauma to cochlear structures using the C40(+) M electrode (MED
      EL, Innsbruck, Austria), which was especially designed for the combined electric
      acoustic stimulation. METHODS: Five human temporal bones were implanted using a
      standard cochlear implant procedure featuring mastoidectomy, posterior
      tympanotomy, and promontory cochleostomy. For the cochleostomy, an inferior
      approach with preservation of the endosteum of the cochlea was used to contribute
      to hearing preservation in the in vivo condition. RESULTS: All insertions of the
      new electrode array were performed into the scala tympani of the cochlea. The
      average insertion depth was 288 degrees. Apically, 4 of the 5 implantations were
      completely atraumatic. One bone showed a rupture of the basilar membrane only at
      the tip of the electrode. However, 4 of the 5 arrays produced severe trauma to
      basal cochlear structures. Two pathomechanisms, the direct traumatization through
      drilling of the cochleostomy or the indirect traumatization via buckling of the
      array could be distinguished. CONCLUSIONS: Due to the reduced contact spacing and
      its flexible body, the C40(+) M electrode is suitable for cochlear implantations
      with hearing preservation and combined electric and acoustic stimulation of the
      auditory system. Modifications of the surgical pathway to the cochlea should help
      to minimize the risk of basal cochlear trauma.

PMID- 15476138
TI  - [Caloric stimulation of the vestibular organ after cochlear implant surgery].
AB  - BACKGROUND: Alterations of the vestibular organ after intracochlear insertion of
      the electrode array in cochlear implant (CI) surgery are estimated in the
      literature to be more than 30 % . By performing a most atraumatic electrode
      insertion following the "soft surgery technique" as described by Lehnhardt , the
      risk of postoperative vestibular dysfunction should be minimised. METHODS: In the
      present study we compared pre- and postoperative results of the caloric
      stimulation test in cochlear implant patients and analysed the influence of
      untimely opening of the perilymphatic space under cochleostomy. In addition we
      used a non-validated questionnaire, asking for continuous postoperative vertigo
      after cochlear implant surgery. RESULTS: From patients with preoperative normal
      or hyperfunction on the implanted ear (n = 32) approximately 16 % showed a
      hypofunction or nonfunction on the implanted side postoperatively, independent of
      the technique of the cochleostomy. Only 12 % (n = 98) of the patients who were
      without vestibular problems preoperatively described postoperative vertigo longer
      than two days in the questionnaires. CONCLUSIONS: Although we found no
      significant difference regarding the influence of the technique of the
      cochleostomy on the preservation of vestibular function, we conclude that the
      concept of an atraumatic electrode insertion reduces the risk of vestibular
      dysfunction after CI-surgery.

PMID- 15476139
TI  - [The monthly interesting case -- case no. 64. Cavernous hemangioma].
AB  - An 89 year old female patient presented with severe epistaxis and nasal
      congestion on the right side. On endoscopic examination of the nasal cavity a
      reddish-bluish tumor has been seen that almost completely filled the posterior
      part of the cavity. In the MRI a highly vasculated tumor was shown. Performing
      transnasal endoscopic surgery the tumor was completely removed from the nasal
      cavity. On histopathologic examination the tumor turned out to be a cavernous
      haemangioma affecting the posterior end of the right turbinate. Cavernous
      haemangiomas in this region are very rare.

PMID- 15476140
TI  - [The value of dynamic posturography (Equitest) in preparing an expert's report].
AB  - BACKGROUND: Expert appraisals of vestibular disorders and their effects on daily
      life are essentially based on an evaluation of the patient's subjectively
      described symptoms. The aim of the present study was to ascertain the extent to
      which dynamic posturography is able to assist in the preparation of expert's
      reports. MATERIAL AND METHODS: 60 patients underwent a survey of their balance
      impairment. Both a nystagmus analysis, with its objective criteria, and dynamic
      posturography were carried out. The investigation into reduction of fitness for
      work (MdE) made reference to the criteria specified in the table by STOLL. The
      data obtained were subjected to both correlation and variance analysis. RESULTS:
      Although the results of this analysis revealed no direct statistical dependency,
      they indicated a tendency for the composite values to be correlated with the
      nystagmus scores and/or the MdE values (when the nystagmus score and/or the MdE
      increases, the composite value decreases). CONCLUSIONS: The Equitest is,
      according to the available data, not able to replace the currently valid MdE
      scores. Nevertheless, it represents a means of providing objective data about the
      vestibulo-spinal reflex. The test also reveals any tendencies towards simulation
      and aggravation. In the context of a specific nystagmus analysis, the Equitest
      offers an additional means of providing an objective background to back up the
      more subjective assessment of MdE.

PMID- 15476141
TI  - [Information about Section of the Vagus Nerve at Tumor Resection].

PMID- 15476142
TI  - [Principals of high frequency surgery].
AB  - Electrosurgical instruments are routinely and daily applied at a variety of
      indications in Otorhinolaryngology. They can be used for cutting, coagulation and
      devitalisation. All have in common that the high frequency energy is transported
      into the tissue via an instrument and by this causes a thermal change. Depending
      on the duration and characteristic of the electricity a vaporisation of the
      tissue is effected through coagulation, devitalisation and carbonisation. The
      knowledge of the effects on the tissue by the choice of the different instrument
      parameters and application systems is essential for an ingenious therapeutically
      indication. In principal the following application methods for electrosurgery by
      modulation of the high frequency parameters are distinguished: the monopolar and
      the bipolar coagulation and devitalisation and the monopolar and the bipolar
      cutting. This article deals with the physical basis, the effects in the tissue as
      well as the single application methods of the high frequency surgery.

PMID- 15476145
TI  - Image of the month. Muehrcke's nails in Peutz-Jeghers syndrome with hepatic
      adenoma.

PMID- 15476146
TI  - Treatment of chronic hepatitis B: who to treat, what to use, and for how long?
AB  - Chronic hepatitis B infection continues to be a major public health concern
      worldwide. The natural history of the disease can be divided into 4 different
      phases: immune tolerance, immune clearance, inactive carrier, and reactivation.
      The goals of treatment are sustained viral suppression, normalization of ALT, and
      improvement in liver histology. Antiviral agents in current use include standard
      interferon-alpha, lamivudine, and adefovir. With an improved understanding of the
      natural history of the disease and a growing repertoire of antiviral drugs, the
      important questions are: who should receive treatment, what is the best agent to
      use, and what is the optimal duration of therapy? Treatment is indicated for
      patients in the immune clearance and reactivation phases. Patients with high
      pretreatment ALT level, detectable HBV DNA in the serum, and active inflammation
      on liver biopsy are predicted to have the highest chance of response to
      treatment. The choice of a particular agent must balance long-term benefits such
      as the likelihood of a sustained response against long-term risks such as drug
      resistance. Interferon treatment leads to a more durable response but is
      associated with unpleasant side effects. Lamivudine is effective and well
      tolerated but requires long-term therapy and is associated with drug resistance.
      Adefovir has proven efficacy and a very low rate of drug resistance but is
      associated with a small risk of reversible nephrotoxicity. For HBeAG-positive
      chronic hepatitis B and HBeAG-negative chronic hepatitis B, the duration of
      interferon therapy is 4-6 months and 12 months, respectively. Duration of
      treatment is at least 1 year with lamivudine and adefovir; longer duration of
      treatment is needed in most patients, but the optimal duration of treatment and
      the criteria for stopping treatment have not been established.

PMID- 15476147
TI  - Whipple's disease.
AB  - Whipple's disease is a rare multisystemic infectious disorder affecting
      predominantly middle-aged men. Clinical manifestations are very variable with a
      very long, insidious, prediagnostic course. Weight loss, chronic diarrhea,
      arthralgias, and low-grade fever are characteristic features in most patients.
      Although gastrointestinal compromise is very common, atypical clinical forms are
      being increasingly recognized. Although a bacterial cause was strongly suggested
      for many years, the infectious agent was elusive until recently. The bacillus
      that was classified as an actinomycete was named Tropheryma whipplei and has
      singular characteristics. It presents affinity for the periodic acid-Schiff
      stain, but it is negative for Ziehl-Neelsen staining and has a characteristic
      trilamellar cell wall. Its genetic material has been recently sequenced, and
      culture was finally performed on a human fibroblast cell line. Pathological
      specimens show macrophage infiltration with mostly intracellular invasion of live
      bacteria. Immunologic factors, such as a subtle defect of cellular immunity
      possibly specific for the Whipple's bacterium, are believed to play a role in
      pathogenesis. The diagnosis requires the histologic assessment of diseased
      tissue, showing the characteristic infiltration, as a first approach, and
      confirmatory tests such as electron microscopy and/or polymerase chain reaction.
      Antibiotic treatment is mandatory and leads to a rapid clinical improvement and
      remission in most patients. Although the rationale for treatment is largely
      empiric, current recommendations include a 2-week parenteral therapy (third
      generation cephalosporin) followed by a long-term therapy with trimethoprim
      sulphamethoxazole. This approach has been shown to reduce the number of relapses
      and was effective for prevention and/or treatment of the neurologic compromise.

PMID- 15476148
TI  - Screening and surveillance in Barrett's esophagus: a call to action.

PMID- 15476149
TI  - The wizards of odds: cost-effectiveness, Barrett's screening, and surveillance
      guidelines.

PMID- 15476150
TI  - Cost-effectiveness model of endoscopic screening and surveillance in patients
      with gastroesophageal reflux disease.
AB  - BACKGROUND & AIMS: Endoscopic screening and periodic surveillance for patients
      with Barrett's esophagus has been shown to be cost-effective in patients with
      esophageal dysplasia, with treatment for esophageal cancer limited to
      esophagectomy. Most gastroenterologists refer patients with high-grade dysplasia
      for esophagectomy, and effective endoscopic therapies are available for
      nonoperative patients with esophageal cancer. The cost-effectiveness of screening
      strategies that incorporate these nonsurgical treatment modalities has not been
      determined. METHODS: We designed a Markov model to compare lifetime costs and
      life expectancy for a cohort of 50-year-old men with chronic reflux symptoms. We
      compared 10 clinical strategies incorporating combinations of screening and
      surveillance protocols (no screening, screening with periodic surveillance for
      both dysplastic and nondysplastic Barrett's esophagus, or periodic surveillance
      for dysplasia only), treatment for high-grade dysplasia (esophagectomy or
      intensive surveillance), and treatment for cancer (esophagectomy or surgical and
      endoscopic treatment options). RESULTS: Screening and surveillance of patients
      with both dysplastic and nondysplastic Barrett's esophagus followed by
      esophagectomy for surgical candidates with high-grade dysplasia or esophageal
      cancer and endoscopic therapy for cancer patients who were not operative
      candidates cost $12,140 per life-year gained compared to no screening. Other
      screening strategies, including strategies that had no endoscopic treatment
      options, were either less effective at the same cost, or equally effective at a
      higher cost. CONCLUSIONS: The cost-effectiveness of screening and subsequent
      surveillance of patients with dysplastic as well as nondysplastic Barrett's
      esophagus followed by endoscopic or surgical therapy in patients who develop
      cancer compares favorably to many widely accepted screening strategies for
      cancer.

PMID- 15476151
TI  - Effect of chronic intake of NSAIDs and cyclooxygenase 2-selective inhibitors on
      esophageal cancer incidence.
AB  - BACKGROUND & AIMS: A rising incidence and a poor survival rate make esophageal
      cancer a major health issue, hence the need for chemoprevention. We investigated
      the effects of the selective cyclooxygenase 2 inhibitors (coxibs), rofecoxib and
      celecoxib, the nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), and
      aspirin on esophageal cancer. METHODS: This nested case-control study used data
      from a government-run insurance database on patients 66 years and older who
      underwent esophageal imaging (esophagogastroduodenoscopy or barium swallow)
      between January 1999 and September 2002. Logistic regression models were used to
      determine the effect of chronic exposure, by using as proxy at least 30 days of
      use of the drugs of interest in the past year, on the occurrence of esophageal
      cancer. RESULTS: The study included 251 cases and all 86,644 eligible control
      subjects. Patients more likely to have esophageal cancer (odds ratio, 95%
      confidence interval) were men (3.42, 2.62-4.48) and older subjects (those 75-84
      years and those > or =85 years: 1.40, 1.08-1.82 and 1.69, 1.05-2.72,
      respectively). Chronic exposure to coxibs or NSAIDs was associated with a
      significant risk reduction for esophageal cancer (0.63, 0.40-0.98 and 0.47, 0.24
      0.93, respectively). Assessed separately, the point estimates were slightly lower
      for rofecoxib than for celecoxib when examining a possible duration-response
      effect, although all 95% confidence intervals overlapped (celecoxib: 0.51, 0.27
      0.98; 0.30, 0.11-0.82; 0.39, 0.14-1.05; rofecoxib: 0.39, 0.16-0.96; 0.37, 0.12
      1.16; 0.33, 0.08-1.36 for exposures of > or =30, > or =60, and > or =90 days,
      respectively). CONCLUSIONS: Chronic intake of rofecoxib and celecoxib and of
      nonselective NSAIDs appears to be associated with a decreased incidence of
      esophageal cancer.

PMID- 15476152
TI  - Relationship of HLA-DQ8 and severity of celiac disease: comparison of New York
      and Parisian cohorts.
AB  - BACKGROUND & AIMS: Celiac disease is a polygenic disorder associated with HLA-DQ2
      or HLA-DQ8, which are present in greater than 90% of patients. The disease is
      considered milder in the United States compared with Europe. We assessed whether
      differences in the frequency of HLA type may account for differences in severity
      of the disease by using cohorts of patients from New York and Paris. METHODS: HLA
      DQ typing was performed on patients with celiac disease in New York and Paris.
      Clinical and pathologic data were compared between the New York and Parisian
      cohorts and also correlated with the different HLA types (HLA-DQ2, HLA-DQ2/-DQ8,
      HLA-DQ8). RESULTS: Among these patients, the disease was milder in the New York
      cohort compared with the Parisian cohort. There were fewer patients with a
      classical presentation (45% and 89%, respectively; P < 0.001) and less severe
      pathology (total villous atrophy, 64% and 89%, respectively; P < 0.05), and less
      marked intraepithelial lymphocytosis (intraepithelial leukocytes [IELs]/100
      enterocytes, 48.1 and 82.5, respectively; P < 0.0001). HLA-DQ2 homozygotes were
      less prevalent in the New York cohort compared with the Parisian cohort (59% and
      79%, respectively; P = 0.08). HLA-DQ8 alleles were more prevalent in the New York
      cohort compared with the Parisian cohort (41% and 21%, respectively; P = 0.026).
      There was, however, no difference in the clinical or pathologic parameters of
      severity when we compared the groups based on HLA type. CONCLUSIONS: HLA-DQ8
      alleles were increased in the New York cohort of patients with celiac disease;
      however, this did not account for less severe manifestations of the disease.

PMID- 15476153
TI  - Effect of renzapride on transit in constipation-predominant irritable bowel
      syndrome.
AB  - BACKGROUND & AIMS: The aim of this study was to evaluate the dose-ranging
      pharmacodynamic effects of renzapride, a 5-hydroxytryptamine 4 (5-HT4) receptor
      full agonist/5-HT3 receptor antagonist, on gastrointestinal transit and symptoms
      in patients with constipation-predominant irritable bowel syndrome (C-IBS).
      METHODS: Forty-eight patients (46 women) with C-IBS underwent recording of
      baseline symptoms for 1 week. Twelve patients per group were randomized (double
      blind, parallel design) to 11-14 days of renzapride (1, 2, or 4 mg) or placebo,
      once daily. Daily bowel habits and weekly satisfactory relief of IBS symptoms
      were recorded. At the end of treatment, gastric emptying (GE), small bowel
      transit (SBT), and colon transit (CT) were measured by scintigraphy. The
      relationship between CT and bowel function was evaluated. RESULTS: A
      statistically significant linear dose response to renzapride was detected for CT
      (GC8 h, P = 0.004; GC24 h, P = 0.056), and ascending colon (AC) emptying t1/2 (P
      = 0.019), but not for GE (t1/2, P = 0.088; or SBT, P = 0.41). AC half-time
      transit (t1/2) for placebo and 4 mg of renzapride were (median) 17.5 vs. 5.0
      hours, respectively. Improved bowel function scores (stool form and ease of
      passage, but not frequency) were significantly (P < 0.05) associated with
      accelerated CT. Pharmacokinetic analysis showed linear kinetics of renzapride
      with a mean t1/2 in plasma of 10 hours. Bowel function and satisfactory relief
      were not significantly altered by renzapride, although a type II error cannot be
      excluded. No significant adverse clinical, laboratory, or electrocardiogram (ECG)
      effects were observed. CONCLUSIONS: Renzapride causes clinically significant dose
      related acceleration of CT, particularly ascending colonic emptying; this
      acceleration of transit is associated with improvement of bowel function in
      female C-IBS patients.

PMID- 15476154
TI  - Flat adenomas in the National Polyp Study: is there increased risk for high-grade
      dysplasia initially or during surveillance?
AB  - BACKGROUND & AIMS: The flat adenoma may be a more aggressive pathway in
      colorectal carcinogenesis. Sessile adenomas from the National Polyp Study cohort
      were reclassified histopathologically as flat or polypoid and compared with
      initial and surveillance pathology. METHODS: A total of 933 sessile adenomas
      detected during 1980-1990 were reclassified as follows: (1) adenoma thickness
      (AT): < or =1.3 mm, and (2) adenoma ratio (AR): adenoma thickness <2x normal
      mucosa thickness. Logistic regression was used to assess whether flat adenomas
      had an effect on risk for high-grade dysplasia initially, and a Cox proportional
      hazards model assessed the risk for advanced adenomas at surveillance. RESULTS:
      The analysis encompassed 8401 person-years of follow-up evaluation. AT and AR
      measures of adenoma flatness were 95% concordant. By the AT measure, flat
      adenomas (n = 474) represented 27% of all baseline adenomas. Flat adenomas were
      found to be no more likely to exhibit high-grade dysplasia than sessile
      (polypoid) or pedunculated adenomas, the odds ratio for high-grade dysplasia was
      1.91 (95% confidence interval [CI], 0.66-5.47; P = 0.23) for sessile (polypoid)
      vs. flat adenomas and 1.78 (95% CI, 0.63-5.02; P = 0.28) for pedunculated vs.
      flat adenomas adjusted for size, villous component, and location, and corrected
      for correlation of risk within an individual patient. Patients with flat adenomas
      at initial colonoscopy were not at greater risk for advanced adenomas at
      surveillance compared with those with polypoid adenomas only, the odds ratio was
      0.76 (95% CI, 0.4-1.42; P = .39), adjusted for multiplicity, age, and family
      history of colorectal cancer. CONCLUSIONS: Flat adenomas identified in the
      National Polyp Study cohort at baseline were not associated with a higher risk
      for high-grade dysplasia initially, or for advanced adenomas at surveillance.

PMID- 15476155
TI  - Long-term treatment of rectovaginal fistulas in Crohn's disease: response to
      infliximab in the ACCENT II Study.
AB  - BACKGROUND & AIMS: The ACCENT II study (A Crohn's Disease Clinical Trial
      Evaluating Infiximab in a New Long-term Treatment Regimen in Patients With
      Fistulizing Crohn's Disease) evaluated the efficacy and safety of infliximab
      maintenance treatment in patients with fistulizing Crohn's disease. This post hoc
      analysis was conducted to determine the efficacy and safety of infliximab therapy
      in women with rectovaginal fistulas. METHODS: All patients received 5 mg/kg
      infliximab intravenously at weeks 0, 2, and 6. Patients who achieved response at
      weeks 10 and 14 then were randomized as responders if they had at least 50% of
      baseline fistulas closed, or as nonresponders, to receive placebo or infliximab 5
      mg/kg every 8 weeks through week 54. RESULTS: Of 282 patients in the ACCENT II
      study, 25 of 138 (18.1%) women had a total of 27 draining rectovaginal fistulas
      at baseline. After infusions of infliximab at weeks 0, 2, and 6, 60.7% (17 of 28)
      and 44.8% (13 of 29) of rectovaginal fistulas were closed at weeks 10 and 14,
      respectively. Among responders, 72.2% (13 of 18) of rectovaginal fistulas were no
      longer draining at week 14. The duration of rectovaginal fistula closure was
      longer in the infliximab 5-mg/kg maintenance group (median, 46 wk) than in the
      placebo group (33 wk). CONCLUSIONS: Infliximab is effective in short-term closure
      of rectovaginal fistulas and maintenance treatment was more effective than
      placebo in prolonging rectovaginal fistula closure.

PMID- 15476156
TI  - Clinical impact of push enteroscopy in patients with gastrointestinal bleeding of
      unknown origin.
AB  - BACKGROUND & AIMS: Despite the frequent use of push enteroscopy (PE), little is
      known of its clinical impact. The aim of this study was to evaluate the impact of
      PE on diagnostic and therapeutic management of patients with gastrointestinal
      bleeding of unknown origin. METHODS: Seventy-five consecutive patients (mean age,
      56 y) referred for PE were included in this 1-year prospective study. Indications
      for PE were overt bleeding in 46 patients (61%) and iron-deficiency anemia in 29
      patients (39%). Before the procedure, the prescribing physicians were asked to
      fill out a questionnaire listing the theoretical patient management plan
      (diagnostic procedures and/or treatment) as if PE were not available. One month
      after PE, the same physicians were asked about: (1) diagnostic procedures
      performed after PE, (2) the final diagnosis, and (3) their opinion of the
      usefulness of PE in clinical management. The clinical impact of PE on diagnostic
      and/or therapeutic management was assessed by 3 study physicians. RESULTS:
      Responses to the 2 questionnaires were obtained for all patients. The diagnostic
      yield of PE was 32% (24 of 75). The clinical impact of PE (changes in diagnostic
      and/or therapeutic management) was 55% (n = 41). PE was perceived as helpful by
      the prescribing physicians in 55% of cases. PE tended to influence patient
      management more in cases of overt bleeding than in cases of occult bleeding (63%
      vs. 41%; P = 0.06). CONCLUSIONS: PE influenced the clinical management of more
      than half the patients with GI bleeding of unknown origin, and was particularly
      useful in patients with overt bleeding.

PMID- 15476157
TI  - The prevalence of alcohol-induced liver disease and hepatitis C and their
      interaction in a tertiary care setting.
AB  - BACKGROUND & AIMS: We examined the prevalence and clinical characteristics of
      alcohol-induced liver disease (ALD) in patients referred to a tertiary care
      center and examined the interaction between ALD and hepatitis C virus (HCV) in a
      longitudinal survival model. METHODS: A total of 1611 patients with chronic liver
      disease referred to a tertiary care center between 1994 and 2001 were analyzed.
      The survival of ALD, HCV, and the combination of the 2 (ALD + HCV) was compared
      in cirrhotic and precirrhotic patients by using Kaplan-Meier estimates. A Cox
      proportional hazards model was used to examine the independent effects of
      predictors on survival. RESULTS: ALD comprised 31% of the cohort, ALD + HCV
      comprised 14%, HCV comprised 22%, and the rest comprised 33%. The survival of
      precirrhotic patients with HCV was significantly better than the survival of
      those with ALD (hazard ratio, 0.27; P = 0.0006) over long-term and 1-year (hazard
      ratio, 0.24; P = 0.016) follow-up periods. There was no difference in survival
      between patients with ALD and ALD + HCV ( P = 0.62). In patients with cirrhosis,
      survival did not differ by cause; decompensated liver disease (hazard ratio,
      1.67; P = 0.004) and continued alcohol abuse (hazard ratio, 2.19; P = 0.002)
      predicted worse survival in this group. CONCLUSIONS: ALD with HCV remains a
      prevalent cause of chronic liver disease in patients referred to a U.S. tertiary
      care center. In patients with ALD, the addition of HCV does not change survival,
      suggesting alcoholism is the driving force for mortality in patients coming to
      clinical attention. In patients with cirrhosis, ongoing excessive alcohol use and
      complications of end-stage liver disease drive mortality, irrespective of the
      underlying cause of chronic liver disease.

PMID- 15476158
TI  - Diagnosing autoimmune hepatitis in children: is the International Autoimmune
      Hepatitis Group scoring system useful?
AB  - BACKGROUND & AIMS: In 1999, the International Autoimmune Hepatitis Group (IAIHG)
      modified a scoring system to differentiate adult patients with definite or
      probable autoimmune hepatitis (AIH) from those with other forms of chronic liver
      disease. We assessed the use of the scoring system in children. METHODS: Twenty
      eight pediatric patients with AIH and/or sclerosing cholangitis were reviewed.
      Clinical, laboratory, and histologic data were collected to score patients both
      before and after standard treatment. RESULTS: There were 8 boys and 20 girls. The
      median age at diagnosis was 11 years (range, 2-16 years). Twenty-one of 28
      children were diagnosed with AIH, 4 as isolated primary sclerosing cholangitis
      (PSC), and 3 as overlap syndrome. At presentation, 18 of 21 (86%) with AIH scored
      as definite AIH and 3 of 21 (14%) scored as probable. No patient clinically
      diagnosed as AIH scored as other. Seven of 28 patients had proven PSC. All
      patients with isolated PSC scored as other. The 3 with overlap syndrome scored as
      definite AIH. When the gamma-glutamyltranspeptidase (GGT) ratio was substituted
      for the alkaline phosphatase (ALP) ratio, 5 patients were reclassified from
      definite to probable AIH. Four of these 5 had an incomplete response to therapy,
      and 2 of 4 have confirmed overlap syndrome. CONCLUSIONS: The IAIHG scoring system
      has a use in children. Patients who fall into the other category should have
      cholangiographic imaging. Using the GGT ratio instead of the ALP ratio in the
      IAIHG score may improve the specificity for children, identifying those likely to
      have biliary disease. When GGT is used, patients classified as needing probable
      pretreatment should be considered for biliary imaging.

PMID- 15476159
TI  - 18-year follow-up study of a prospective randomized trial of hepatitis B
      vaccinations without booster doses in children.
AB  - BACKGROUND & AIMS: The long-term immunogenicity and efficacy of hepatitis B virus
      (HBV) vaccination remain to be defined. We aimed to examine the long-term
      immunogenicity and efficacy of HBV vaccination with 3 different regimens over 18
      years of follow-up. METHODS: A total of 318 Chinese subjects receiving 3
      different regimens of HBV vaccination (2-dose recombinant vs. 3-dose recombinant
      vs. 3-dose plasma-derived vaccines) without receiving a booster dose were
      recruited. The HBV serologic markers, including hepatitis B surface antigen
      (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to
      hepatitis B core antigen (anti-HBc), were determined at yearly follow-up. After
      18 years, 88 subjects were still being followed up. RESULTS: Compared with
      subjects receiving the 2-dose regimen, subjects receiving the 3 dose regimens had
      a significantly higher geometric mean titer of anti-HBs and a higher proportion
      had anti-HBs titers > or =10 mIU/mL during the 18 years of follow-up. There were
      no differences in these 2 parameters between subjects receiving the 3-dose
      recombinant and subjects receiving the 3-dose plasma-derived vaccines. A total of
      88 anamnestic responses were documented in 70 subjects (8 with initial anti-HBs
      titers <100 mIU/mL at 12 months and 7 with anti-HBs titers <10 mIU/mL before the
      anamnestic responses). No subject became positive for HBsAg. Three subjects had
      benign breakthrough HBV infection without leading to chronicity indicated by
      isolated anti-HBc positivity. CONCLUSIONS: There was less long-term
      immunogenicity associated with the 2-dose regimen when compared with the 3-dose
      regimens of HBV vaccination. Because of the highly effective anamnestic
      responses, a booster dose was not necessary at least up to 18 years after the
      primary vaccination.

PMID- 15476160
TI  - [Analysis on FUT1 and FUT2 gene of 10 para-Bombay individuals in China].
AB  - OBJECTIVE: This is a study on the allele composing of ABO, FUT1 and FUT2 gene
      loci of 10 para-Bombay individuals in China. METHODS: Ten samples coming from
      different districts of China were suspected of para-Bombay phenotype by primary
      serology tests. Routine and absorb-elution tests were conducted to identify their
      ABO type, and duplex polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) was applied to getting their ABO genotype. Most of them
      were submitted to a test of their Lewis type as well. Then through direct DNA
      sequencing with PCR products of FUT1 and FUT2 genes, the genotypes of their H and
      SE gene loci were analyzed. RESULTS: It can be confirmed that the 10 samples are
      para-Bombay. All of their ABO genotypes are consistent with the serological
      absorb-elution results and the substances detected results in saliva. Seven out
      of 10 have recessive homozygous gene at their H locus. Each phenotype of h1h1
      (nt547-552Deltaag), h2h2 (nt880-882Deltatt) and h4h4 (nt35 t-->c) are ascertained
      in 2 individuals; moreover, h3h3 (nt 658 c-->t) is identified in one individual.
      The rest are hh heterozygous individuals: one is h3/h(new-1); the other is
      h2/h(new-2); the last one is h1/h2. The h(new-1) (nt586 c-->t) allele has a point
      mutation at nt 586 C to T, which leads a nonsense mutation Gln(CAG) to stop
      (TAG).The second h (new-2) (nt328 g-->a) has an nt328 G to A missense
      mutation,which leads Ala (GCC),was replaced by Thr (ACC) at 110 amino acid
      position. All the 10 samples have Se (nt357 c-->t) synonymous mutation. One Bm(h)
      (B/O) individual with h4h4 phenotype has a Se(w)(nt357 c-->t; nt385 a-->t)
      allele, whose Lewis type is Le(a+b+). Moreover, the authors detected a (nt716 g-
      >a) mutation in two samples' Se gene. CONCLUSION: Four kinds of known h alleles
      (h1-h4), 2 kinds of novel non-functional FUT1 alleles, a Se(w) allele, and a
      novel SeG716A polymorphism in Chinese para-Bombay individuals were detected. At
      the same time, the authors noticed that all the 10 samples have the nt357 c-->t
      mutation in their FUT2 gene.

PMID- 15476161
TI  - [Establishment of CPP-SOM integrated cDNA microarray technology].
AB  - OBJECTIVE: To get an insight into the molecular mechanisms of diseases
      development and targeted therapy at the transcriptome level and search for
      potential therapeutic targets. METHODS: The present researchers established a
      cDNA microarray platform and applied component plane presentation integrated self
      organizing map (CPP-SOM) to the microarray data obtained from a differentiation
      model, all trans retinoic acid-induced differentiation in NB4 cells. RESULTS: The
      platform included 12630 unique clones, including 9436 known genes. By CPP-SOM,
      the researchers were able to not only well classify the regulated genes into
      functionally distinct categories but also depict transcriptional changes
      throughout the process of the development of diseases or drug treatment.
      CONCLUSION: The platform has proven to be steady and reliable, and the CPP-SOM
      could serve as an important and good tool for analysis of microarray data.

PMID- 15476162
TI  - [Differential expression of motility-related protein-1/CD9 gene in gastric
      cancers and premalignant lesions].
AB  - OBJECTIVE: To clone and identify gastric cancer-related genes and explore the
      possible pathogenic mechanism of gastric cancer. METHODS: The differentially
      expressed cDNA bands were isolated by fluorescent mRNA differential display in
      gastric cancer specimens, matched normal gastric mucosa and premalignant lesions.
      The motility-related protein-1 (MRP-1/CD9) gene was one of the down-regulated
      genes. MRP-1/CD9 gene expression in different kinds of gastric tissue was
      analyzed by Northern blot and reverse transcription-polymerase chain reaction (RT
      PCR). RESULTS: MRP-1/CD9 expression was down-regulated in all gastric cancer
      tissues. Northern blot analysis confirmed this differential expression. RT-PCR
      analysis showed that the MRP-1/CD9 gene expression was much lower in gastric
      cancers(0.31+/-0.18) than in the matched normal gastric tissue (0.49+/-0.24) and
      in the premalignant lesions (0.47+/-0.18) (P<0.05), and its expression in
      intestinal type gastric cancer (0.38+/-0.16) was higher than that in diffuse type
      gastric cancer (0.22+/-0.17) (P<0.05). CONCLUSION: The MRP-1/CD9 gene expression
      was down-regulated in gastric cancer, its expression was probably related to the
      carcinogenesis and histology types of gastric cancer.

PMID- 15476163
TI  - [OAZ gene polymorphism in Chinese patients with systemic lupus erythematosus].
AB  - OBJECTIVE: To observe the association between systemic lupus erythematosus (SLE)
      and gene polymorphisms of OLF-1/EBF associated zinc finger protein(OAZ). METHODS:
      Verified single nucleotide polymorphisms (SNPs) with relatively high
      heterozygosity were chosen for allelic discrimination in 244 Chinese SLE
      pedigrees. Then transmissions of single SNP, and haplotypes were calculated by
      Genehunter software..OAZ mRNA level was also measured for comparing gene
      expression in patients of different haplotypes. RESULTS: Genotyping of five SNPs
      within OAZ gene introns indicated there was no preferential transmission of
      single SNP, and haplotype T-A-G-G for rs1344531-rs2080353-rs933564-rs1345431
      showed only weak linkage with the disease (P=0.04). However, haplotypes combining
      SNPs and the SLE-associated D16S517 allele showed significant association with
      SLE susceptibility (for rs933564-d16s517 G-271bp t:non-t=93:29 P<0.000001, for
      rs2080353-rs933564-d16s517 A-G-271bp t:non-t=88:35 P=0.000002). The haplotype A-G
      271bp-G of Rs2080353-rs933564-D16s517-rs1345431 was also transmitted to patients
      preferentially (P=0.0084) and it showed a tendency to affect gene expression.
      CONCLUSION: Special polymorphism haplotype of OAZ gene is associated with Chinese
      SLE. OAZ may suggest a new pathway for lupus.

PMID- 15476164
TI  - [Alpha 2 codon 30 deletion (deltaGAG) causing non-deletional hemoglobin H disease
      in Guangxi province].
AB  - OBJECTIVE: To analyze genotypic profiles and understand the relationship between
      the genotype and phenotype of Hb H disease in Guangxi province. METHODS:
      Hematologic and Hb analyses on the cases were performed to detect their alpha
      thalassemia genotypes using PCR method and DNA sequencing. RESULTS: An unusual
      case was identified in one of the 298 patients with Hb H disease diagnosed in the
      First Affiliated Hospital of Guangxi Medical University from October 2002 to
      November 2003. The 25-year-old male patient, a native of Yulin in Guangxi
      province, had had jaundice and splenomegaly since childhood, and he had never
      received blood transfusion. Hematologic examinations revealed his hemoglobin 107
      g/L, RBC 4.9+10(12) g/L, MCV 76.2 fl, MCH 21.8 pg, MCHC 287 g/L, HCT 0.373,
      reticulocyte 3%. Hb analysis showed the level of Hb H + Hb Bart's 34.41%. PCR and
      DNA sequencing confirmed the genotype of a deletion at codon 30 of alpha2 globin
      gene and SEA alpha-thalassemia-1. CONCLUSION: This unusual case had no anemia,
      but had higher level of Hb H and Hb Bart's when compared to those non-deletional
      Hb H disease cases such as Hb CS-H, HbQS-H and alpha2 codon 31 mutation combined
      with SEA alpha-thalassemia-1 previously reported in mainland China. The discovery
      and recognition of this gene mutation and related genotype and phenotype is of
      importance to the genetic counseling and prenatal diagnosis in Guangxi province
      where the incidence of alphathalassemia is very high.

PMID- 15476165
TI  - [Study on the relationship of CTLA-4 -318, +49 polymorphisms with autoimmune
      hepatitis and primary biliary cirrhosis in a Chinese population].
AB  - OBJECTIVE: To investigate the association between Chinese patients with
      autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and the polymorphisms
      of cytotoxic T lymphocyte -associated antigen-4 (CTLA-4) gene promoter (-318) and
      exon 1 (+49). METHODS: The CTLA-4 promoter (-318 T/C) and exon 1 (+49A/G)
      polymorphisms were genotyped via restriction fragment length polymorphism methods
      in 62 Chinese AIH patients, 77 Chinese PBC patients and 160 healthy controls.
      RESULTS: There was no difference in the distribution of CTLA-4 promoter -318 T/C
      polymorphisms between AIH patients and controls, but the C allele frequency was
      significantly increased in patients with AIH, compared to controls (P=0.02,
      OR=2.43). The distribution of CTLA-4 gene exon 1 49 A/G genotypes exhibited
      significant difference between PBC patients and controls (P=0.006), and the
      frequency of G allele showed a significant increase in PBC group as compared with
      controls (P=0.0046, OR=1.8). Although the genotype distribution of the CTLA-4
      exon 1-promoter gene displayed no significant difference between AIH and PBC
      patients and controls, the occurrence of GG-CC was increased in the patients of
      the two groups (AIH: 32.3%, PBC: 37.7%; control: 22.5%). CONCLUSION: The above
      findings suggest that the polymorphisms of CTLA-4 gene probably confer
      susceptibility to AIH and PBC in the Chinese population.

PMID- 15476166
TI  - [Idiopathic male infertility and partial copy deletion of DAZ gene family].
AB  - OBJECTIVE: To analyze the pattern and prevalence of partial copy deletion of
      deleted-in-azoospermia (DAZ) gene in the azoospermia factor C(AZFc) region of
      patients with idiopathic azoospermia or severe oligozoospermia. METHODS: sY581
      and sY587 in DAZ gene region were analyzed by polymerase chain reaction
      restriction length polymorphism(PCR-RFLP) for its deletion in 197 patients with
      azoospermia, 166 patients with severe oligozoospermia, and 210 fertile men as
      controls. RESULTS: Deletion of both DAZ1 and DAZ2 was detected in 18 patients
      with azoospermia and 10 with severe oligozoospermia, and the prevalence was 9.1%
      and 6.0% respectively. There was significant difference in deletion rate between
      the cases and controls. CONCLUSION: The frequency of partial copy deletion of DAZ
      gene in Chinese idiopathic azoospermia or severe oligozoospermia patients is much
      higher than that of fertile controls, suggesting that the deletion of DAZ1/DAZ2
      may be one of the important genetic etiological factors of spermatogenesis
      damage. The pattern and prevalence of DAZ partial copy deletion are similar to
      those of Caucasians populations, and detection of DAZ gene partial copy deletion
      by PCR-RFLP may be adopted as an additional clinical gene diagnostic measure
      after AZF microdeletion detection.

PMID- 15476167
TI  - [Identification of G6PD gene variants from Hakka population in Guangdong
      province].
AB  - OBJECTIVE: Studying on G6PD polymorphism from Hakka population in Guangdong
      province. METHODS: Identifying the variants of G6PD gene and determining the
      frequencies respectively with the use of amplified refractory mutation
      system(ARMS), polymerase chain reaction-single strand conformation
      polymorphism(PCR-SSCP) and ABI 3100 DNA sequencing technologies. RESULTS:
      Mutations of G6PD gene in cDNA 1388 (G-->A), 1376 (G-->T), 95 (A-->G), 392 (G-
      >T), 1024 (C-->T), 1311 (C-->T) have been found. CONCLUSION: G6PD cDNA 1388 (G-
      >A), 1376 (G-->T), 95(A--> G), 392 (G-->T), 1024 (C-->T) and 1311 (C-->T)
      accompanied with intron 11 (93 T-->C) are the common mutations in Chinese
      population. cDNA 1388 (G-->A), cDNA 1376 (G-->T) are the most popular G6PD gene
      variants in Hakka population. In this study, no new type of G6PD gene mutation
      was found in the Hakkas of Guangdong.

PMID- 15476168
TI  - [TH gene mutation in Chinese patients with autosomal recessive dopa-responsive
      dystonia].
AB  - OBJECTIVE: To explore the mutation of tyrosine hydroxylase(TH) gene in Chinese
      patients with autosomal recessive(AR) dopa-responsive dystonia(DRD) and to lay a
      solid basis for gene diagnosis of AR-DRD in China. METHODS: Mutation analysis of
      TH gene was performed in 5 probands with AR-DRD and 2 sporadic patients with DRD
      by use of polymerase chain reaction-single strand conformation polymorphism (PCR
      SSCP) combining DNA direct sequencing. RESULTS: The PCR-SSCP analysis and DNA
      direct sequencing following PCR revealed no mutation in all the 14 exons of TH
      gene. CONCLUSION: The mutation rate of TH gene in Chinese patients with AR-DRD is
      low, hence suggesting the genetic heterogeneity and a new locus for AR-DRD.

PMID- 15476169
TI  - [Study on mutation of presenilin-1 gene in familial Alzheimer's disease].
AB  - OBJECTIVE: To explore the role of the mutation of presenilin-1 exon 6 in
      pathogenesis of Alzheimer's disease(AD) patients. METHODS: Exon 6 of presenilin-1
      was analyzed by use of polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) and DNA analyzer technique in 2 patients with familial
      AD, 53 patients with sporadic DA, 60 patients with vascular dementia(VD) and 90
      normal controls. RESULTS: Mobility shift of SSCP in exon 6 of presenilin-1 was
      detected in 2 cases with FAD, 4 cases with SDA and 1 case with VD. Two missense
      mutations were found in the patients by DNA sequence analysis, one mutation was
      1123 nt C-->G(Cys 23 Trp) and the other was 1300 nt A-->C(Asp 200 Ala).
      CONCLUSION: Mutations in exon 6 of presenilin-1 existed in the patients with FAD
      and SDA, and the two missense mutations were probably pathological by nature.

PMID- 15476170
TI  - [A pedigree with myotonic dystrophy: non-CTG, non-CCTG repeat expansion].
AB  - OBJECTIVE: Two genetic loci are associated with the myotonic dystrophy (DM)
      phenotype: DM1 DMPK on chromosome 19, and DM2 ZNF9 on chromosome 3. The aim of
      this study was to investigate the molecular genetics of a pedigree with DM.
      METHODS: In twenty-six individuals from a family with DM, the CTG repeats in DMPK
      and CCTG repeats in ZNF9were evaluated genetically, using Long Expand trade mark
      Template polymerase chain reaction (PCR), Southern blotting and genomic scanning.
      RESULTS: The numbers of CTG and CCTG repeat were all in normal range. There was
      no significant difference between the CTG repeat size in DMPK gene and that 4
      years later from the same individual. The Lod score values with short tandem
      repeats STR markers chosen in 19q and 3q were all smaller than 1, which suggested
      that no STR marker was linked with this DM family. CONCLUSION: There might be
      some other mutant in this DM pedigree. Further study should be done to find the
      genetic basis of this pedigree.

PMID- 15476171
TI  - [A study of quadriplex PCR with chimeric primers for short tandem repeats loci].
AB  - OBJECTIVE: To establish a simplified method of multiplex PCR based on chimeric
      primers for STR loci. METHODS: A set of chimeric primers and universal primers
      were designed to carry out a multiplex PCR for amplifying four short tandem
      repeats(STR) loci. Then the amplified STR loci were detected by polyacrylamide
      gel electrophoresis and the gels were sliverstained. RESULTS: A quadriplex STR
      system was developed on the basis of both chimeric and universal primers.
      CONCLUSION: The STR multiplex PCR based on both chimeric and universal primers
      hss been achieved readily and reproducibly by simple adjustment of the individual
      primer concentrations. The use of chimeric primers provides a method for primer
      design that eliminates the multiple optimization steps involved in developing the
      multiplex PCR.

PMID- 15476172
TI  - [Rapid molecular diagnosis of trisomy 21 using the PCR-STR-SSCP technique].
AB  - OBJECTIVE: Developing a PCR-based method to diagnose trisomy 21 directly by
      alternative detection of the SSCP profiles of the STR fragments amplified.
      METHODS: The DNA samples from 19 trisomy 21 patients, 3 at-risk fetuses of
      trisomy 21 and a total of 44 samples from their parents as controls were drawn
      for this study, in which the trisomy 21 was determined by G-band karytyping. Two
      polymorphic STR at D21S11 and D21S1411 served as the gene markers, and two
      separate PCR-amplified primers were designed.The STR-amplicons denatured were
      subjected to polyacrylamide gel electrophoresis for SSCP analysis. RESULTS: This
      assay can identify three STR fragments representing parents' chromosome 21 by
      detecting the electrophoresis separation profiles of PCR-amplified fragments.
      With the use of this assay, the authors analyzed the 22 cases of trisomy
      21;accurate diagnoses were made except for one case in which the electrophoresis
      pattern at D21S11 site could not present the diagnostic information because of
      the homozygous state of this family. The 3 at-risk fetuses were found to be the
      trisomy 21 patients, followed by confirmation of the results by G-band karytyping
      of aborted samples. CONCLUSION: The present PCR-STR-SSCP assay can be applied as
      a simple, rapid and accurate method in the prenatal diagnosis and genetic
      screening of trisomy 21.

PMID- 15476173
TI  - [Detection of ALK gene translocation by fluorescence in situ hybridization in
      paraffin-embedded anaplastic large cell lymphoma tissue and its significance].
AB  - OBJECTIVE: To compare the value of fluorescence in situ hybridization(FISH) with
      that of immunohistochemistry in detecting ALK gene translocations and ALK fusion
      protein in anaplastic large cell lymphoma (ALCL) and investigate the possibility
      of FISH working on paraffin-embedded ALCL tissue. METHODS: Dual-color FISH and
      ALK-1 immunohistochemistry were used to detect ALK gene translocation and ALK
      fusion protein in 22 paraffin-embedded ALCL cases. RESULTS: The digestion time of
      tissue section was a key-point in the operating of FISH in paraffin-embedded
      tissue. ALK fusion protein expression was detected with ALK-1 antibody in 12 of
      the 20 systemic ALCL; it was not detected in 2 primary cutaneous ALCL. The Dual
      color FISH results were 100% consonant with the immunohistochemical results.
      CONCLUSION: (1) Generally, immunohistochemical method is the first choice in
      detecting ALK gene translocation, but when conditions permit, FISH can be the
      first choice. (2) By the optimization of experimental conditions, FISH can be
      successfully performed on paraffin-embedded tissue.

PMID- 15476174
TI  - [Strategy for the identification of amplified genes in tumors].
AB  - Amplification of genomic DNA is often observed in tumors. The identification of
      genes in amplified regions may be helpful to the discovery of oncogenes
      associated with a specific tumor. Array-based comparative genomic hybridization
      and restriction landmark genomic scanning are applicable to the definition of
      such regions. The copy number alterations of target genes present in these
      regions and the levels of their mRNA and protein can be characterized by
      quantitative PCR and tissue microarray staining with immunohistochemistry.
      Transfection, RNA interference, cDNA microarray or reverse transcription
      multiplex ligation-dependent probe amplification will facilitate demonstrating
      the role of such amplified genes in the pathogenesis of a specific tumor.

PMID- 15476175
TI  - [Molecular pharmacogenetic studies of drug responses to obsessive-compulsive
      disorder and six functional genes].
AB  - OBJECTIVE: To investigate the associations between the drug responses to
      obsessive -pulsive disorder (OCD) and six functional genes related with serotonin
      and dopamine. METHODS: One hundred and thirteen OCD nuclear families were
      collected. The OCD patients were treated with serotonin reuptake inhibitors
      (SRIs) for 8 weeks and the drug responses were assessed using the Yale-Brown
      obsessive-compulsive scale (Y-BOCS). The patients were divided into drug
      responders group and non-responders group according to the reducing rate of Y
      BOCS score. The genotypes of six genes were determined with the Amp-FLP and Amp
      RFLP techniques and analyzed by transmission disequilibrium test (TDT). The six
      genes are serotonin 2A receptor (5-HT2A), serotonin transporter (5-HTT), dopamine
      D2 receptor ( DRD2), dopamine D4 receptor (DRD4), catechol-O- methyltransferase
      (COMT) and monoamine oxidase A (MAOA). RESULTS: No association was found between
      the six genes and different drug responses groups. However, there was significant
      difference between the drug responders and non-responders in homozygosity at the
      5-HT2A -1438G/A locus (chi(2)=4.69, P=0.03). CONCLUSION: The results suggested
      that the 5-HT2A may play some roles in the effects of drug treatment on OCD.

PMID- 15476176
TI  - [One family investigation and pathogeny research on ectrodactyly, absence of
      radius side part palm and split foot malformation].
AB  - OBJECTIVE: The paper is a study on the clinical symptoms and pathogeny of
      ectrodactyly and absence of radius side part palm and split foot malformation of
      some patients in one family. METHODS: Based on the patient family investigation,a
      normal control group and a patient group were established. Then, polymerase chain
      reaction technique was used for DNA sequencing and analysis of the two groups for
      their exons 5-8 gene group DNA of P63 gene. RESULTS: The medical examination
      found that the patients' upper bilateral limbs are short of thumbs, forefingers
      and middle fingers, and have radius side part palm and double lower limbs foot
      clefts malformation. The pathogeny research revealed that the PCR expansion
      pieces of the exons 5-8 of P63 are 284 bp, 259 bp, 245 bp and 259 bp
      respectively, and the size of the expansion piece of the patients was the same as
      that of the normal people group. However, a respective comparison between the DNA
      serial of the expansion piece of the patient and that of the normal people group
      and that of the P63 gene in the human gene bank showed that mutation occurs at
      the number 665 base pair of exon 5 of P63, namely a mutation from G to A.
      CONCLUSION: The ectrodactyly, absence of radius side part palm and split foot
      malformation are caused by the mutation of base pair at number 665 of the exon 5
      of P63.

PMID- 15476177
TI  - [Detecting microdeletions of the Y chromosome in patients with high follicle
      stimulating hormone azoospermia].
AB  - OBJECTIVE: To explore the relationship between the patients' high follicle
      stimulating hormone (FSH) azoospermia and microdeletions in Y chromosome.
      METHODS: Eleven sequence tagged sites (STSs) in Yq were detected by PCR in 16
      male patients' high FSH azoospermia. RESULTS: Microdeletions were observed in 6
      of 16 male patients and the deletion rate was 37.5%(6/16). Five types of
      microdeletions were detected: AZFc(SY152), AZFc (SY152+SY254)+AZFd (SY153), AZFc
      (SY152+SY254+SY255)+AZFd (SY153), AZFc (SY152+SY158+SY255)+AZFd (SY153),and AZFb
      (SY130)+AZFc (SY158+SY254+SY255)+AZFd (SY153) respectively. CONCLUSION:
      Microdeletion of Y chromosome was one of the important reasons of the patients'
      high FSH azoospermia. Before the application of assisted-reproductive technology
      (ART) to the patients, it is necessary to detect the microdeletions, especially
      AZFc and AZFd.

PMID- 15476178
TI  - [Preimplantation genetic diagnosis for a patient with Robertsonian
      translocation].
AB  - OBJECTIVE: To investigate the feasibility and risk of preimplantation genetic
      diagnosis (PGD) for screening normal offspring of Robertsonian translocation
      carriers. METHODS: This case was clinically diagnosed as primary infertility for
      6 years; the husband was found to have chromosome der (13;14) (q10;q10) and
      oligozoospermia. For the solution of the couple's problem, controlled ovarian
      hyperstimulation (COH) and intracytoplasmic sperm injection (ICSI) were performed
      to obtain embryos. The embryos were drilled in zona by acidified Tyrode's
      solution at 6-8 cell stage (day 3 post-fertilization) and a single blastomere was
      removed from each embryo. All blastomeres were analyzed by fluorescence in situ
      hybridization (FISH) using the double color probes LSI 13q labeled by
      SpectrumOrange and Tel 14q labeled by SpectrumGreen. The embryos biopsied were
      cultured at once and the normal ones selected were transferred the next day.
      Prenatal diagnostic techniques were used to detect the karyotype of fetus at 18
      weeks of gestation. RESULTS: Unbalanced, normal or balanced, and unclear embryos
      were separated. The couple obtained 50a (4/8)normal or balanced,and 37.5a
      (3/8)unbalanced, and 12.5a (1/8) unclear embryos. A singleton pregnancy followed,
      and the karyotype of the fetus (46,XY) was detected by prenatal diagnostic
      techniques. CONCLUSION: PGD is useful for screening out unbalanced embryos and is
      very valuable for solving the reproductive problem of Robertsonian translocation
      carriers and for avoiding fetal beings with severe disorders.

PMID- 15476179
TI  - [Study on the polymorphism of interleukin-1 gene and the susceptibility to
      essential hypertension].
AB  - OBJECTIVE: To make investigations on the polymorphism of interleukin-1 (IL-1)gene
      in Chinese Han population, on its association with essential hypertension, and on
      the relationship between the genotype of IL-1 and susceptibility to essential
      hypertension. METHODS: The polymorphisms of IL-1 gene in Han population of Hubei
      province, including polymorphisms of IL-1alpha (-889C/T), IL-1beta (-511C/T),IL
      1beta (+3953C/T), IL-1Ra(+8006T/C) and IL-1Ra (variable number of tandem repeat,
      VNTR), were analyzed by polymerase chain reaction (PCR) and a combination of PCR
      restriction fragment length polymorphism methods in 152 patients with essential
      hypertension and 168 healthy controls. RESULTS: The polymorphism distributions of
      IL-1alpha (-889C/T), IL-1beta (+3953C/T), IL-1Ra (+8006T/C) and IL-1Ra (VNTR)
      showed no differences between the essential hypertension group and control group,
      but the IL-1beta (-511C/T) exhibited a significant difference between the two
      groups. CT genotype carriers were at increased risk for essential hypertension
      (OR=2.54, 95%CI: 1.41-4.58), compared with healthy controls. CONCLUSION: The
      polymorphism of promotor region -511C/T in IL-1beta gene is probably associated
      with the susceptibility to essential hypertension.

PMID- 15476180
TI  - [Use of specific antibody to detect fetal erythroblasts in maternal circulation].
AB  - OBJECTIVE: To investigate the feasibility of using immunohistochemical technique
      to detect the presence of fetal erythroblasts in the maternal circulation for
      prenatal diagnosis. METHODS: Maternal blood was obtained from 30 pregnant women
      at 8 to 26 weeks of gestation. Nucleated red blood cells (NRBCs) were separated
      with Percoll using a discontinuous density gradient method, and then smeared on
      microscope slides using cytocentrifugation. Slides were stained with antibody
      against the gamma-chain of fetal hemoglobin (HbF). All positive NRBCs were
      collected by micromanipulator under microscopic observation, and then amplified
      by improved primer extension preamplification(PEP). Sex and Duchenne's musclar
      dystrophy (DMD) genetic diagnosis were determined from a small aliquot of the PEP
      reaction. RESULTS: NRBCs stained with HbF were found in all of the blood from the
      30 pregnant women at 8 to 26 weeks of gestation. 17 male fetuses and 13 female
      fetuses were detected in the 30 cases. These results coincided with those of
      induced labor or amniotic fluid control, and 8 fetuses at the risk of DMD were
      diagnosed. CONCLUSION: This diagnostic method using immunohistochemical technique
      to mark fetal NRBC shows good application prospects.

PMID- 15476181
TI  - [Beta-thalassemia mutations and single nucleotide polymorphism at -158 of Ggamma
      globin gene associated with altered levels of Hb F in beta-thalassemia
      heterozygotes].
AB  - OBJECTIVE: To investigate the relationship of beta-thalassemia mutations and the
      single nucleotide polymorphism(SNP) at position -158 of (G)Gamma-globin gene to
      the altered levels of fetal hemoglobin(Hb F) of beta-thalassemia heterozygotes.
      METHODS: Hb F was quantitated by alkali denaturation; beta-thalassemia mutations
      were determined by PCR-allelic specific oligonucleotide(PCR-ASO). The SNP at -158
      was analyzed by amplification of (G)Gamma gene promoter fragments from the DNA,
      followed by Xmn I restriction enzyme digestion. RESULTS: Among 63 cases with beta
      thalassemia trait, 15 had Hb F levels above 2% (2.06%-10.44%). Six beta
      thalassemia mutations were observed in this study, namely CD41/42(-TTCT), CD17(A-
      >T), nt28 (A-->G), CD71/72(+A), IVS-II-654(C-->T) and IVS-I-1(G-->T). There was
      no difference in the incidence of beta-thalassemia heterozygotes of CD41/42,
      CD17, CD71/72 and IVS-II-654 between 15 cases with Hb F>/=2% and 48 cases with Hb
      F<2%. Ten (15.9%) heterozygotes of (G)Gamma-158(C-->T)were detected among 63
      cases, and 8 of them (53.33%) belonged to the group of Hb F>/=2% while the
      remaining 2 cases (4.17%) were in the group of Hb F<2%. CONCLUSION: beta
      thalassemia mutations of CD41/42, CD17, CD71/72, IVS-II-654 had no influence on
      Hb F levels, but (G)Gamma-158(C-->T) had a strong association with moderately
      increased Hb F levels in beta-thalassemia heterozygotes in the Guangxi area of
      China.

PMID- 15476182
TI  - [Application of long distance-PCR to hemophilia A carrier detection and prenatal
      diagnosis].
AB  - OBJECTIVE: To establish an effective laboratory examination system for carrier
      detection and prenatal diagnosis of haemophilia A (HA). METHODS: Twenty-five
      carriers of severe HA were directly detected by long-distance PCR (LD-PCR) in
      search of the factor FVIII (FVIII) gene inversion. Prenatal diagnosis was carried
      out using pregnant woman's venous blood sample, husband's venous blood sample and
      fetal navel venous sample at 20-24 weeks of gestation. The plasma coagulation
      factor VIII activity (FVIII:C) was detected by one-stage method. The
      concentration of von Willbrand factor (Vwf) was assayed by ELISA. Prenatal
      diagnosis was finally made by LD-PCR. The results of LD-PCR were proved by DNA
      sequencing. RESULTS: Eight out of 25 cases were diagnosed as having FVIII
      geneinversion. Four of these 8 carriers underwent the LD-PCR for prenatal
      diagnosis, and 2 of them had to terminate pregnancy because their fetuses were
      diagnosed as having HA. The other two carriers were finally diagnosed to have
      normal fetuses by combined use of LD-PCR with plasma FVIII:C, vWF in pregnant
      woman's venous blood, husband's venous blood and fetal navel venous blood, and
      the one-year follow-up study demonstrated that the babies were normal and living
      well. CONCLUSION: LD-PCR technique was adopted in this study to detect the factor
      VIII gene inversion; it could accurately and rapidly diagnose the severe cases of
      HA and could be used for the HA carriers in need of pregnant diagnosis.

PMID- 15476183
TI  - [Absence of evidence for the association of single nucleotide polymorphisms in
      Annexin A1 gene with type 2 diabetes in Chinese].
AB  - OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) in the annexin
      A1(ANXA1) gene and to analyze the association of these SNPs with type 2 diabetes
      in Shanghai Han population. METHODS: SNPs in the promotor and exon regions
      (including intron sequence near splicing site) in the ANXA1 gene were screened by
      direct sequencing in 24 type 2 diabetes patients and were further genotyped by
      direct sequencing in another 171 type 2 diabetes patients and 189 normal control
      subjects. RESULTS: The total sequence of ANXA1 gene is 6798 bp. And 7 SNPs were
      found; among them, 2 SNPs (-7974 C>T and -7040 G>T) were in promotor region, 3
      SNPs in intron regions (+9059 A>G, +9204 C>T, +10486 A>G), 1 SNP in 5'
      untranslation region (-6614 A>G) and 1 SNP in coding regions (+1784 A>G). These 7
      SNPs were genotyped further and the results revealed that the allele frequencies
      of these SNPs showed no significant difference between the diabetic and the
      control groups (P>0.05). CONCLUSION: There is no association of these SNPs in
      ANXA1 gene with type 2 diabetes in Shanghai Han population.

PMID- 15476184
TI  - [Clinical and biological characteristics in childhood acute myeloid leukemia with
      8;21 translocation].
AB  - OBJECTIVE: To investigate the clinical and biological characteristics of
      childhood acute myeloid leukemia(AML)with 8;21 translocation. METHODS: A
      retrospective analysis including clinical information, cell morphology,
      chromosome, immunophenotype and molecular biology was performed on 41 cases of
      childhood t(8;21)AML. The control group included 19 cases of AML without t(8;21)
      translocation detected during the same period. RESULTS: The 41 cases of
      t(8;21)AML accounted for 68.3% of 60 continuous childhood AML patients. Among
      them, classical t(8;21) translocation was seen in 29 cases; variant t(8;21)
      translocation, simple 8q-, near-tetraploidy characterized by the duplication of
      t(8;21) translocation each came into view in 2 cases; and cryptic t(8;21)
      translocation was seen in 6 cases. Thirty seven cases (80.4%) belonged to M2
      subtype of AML. Most of them had the morphological changes such as the leukemia
      cells' indent nucleus with a light stain region of perinucleus, basophilic
      cytoplasm, differentiation with maturation, megaloblastoid changes and nuclear
      cytoplasm imbalance; the high expression of CD13 antigen; and the AML1/ETO fusion
      transcript in 23 cases examined by reverse transcription-polymerase chain
      reaction (RT-PCR) assay, including 6 cases with normal karyotype. The difference
      in complete remission rate between t(8;21) positive patients group and t(8;21)
      negative patients group was not significant in statistics (82.4% vs 75%, P>0.05).
      However the difference in recurring rate of the leukemia was statistically
      significant (10.7% vs 41.7%, P<0.05). CONCLUSION: t(8;21)AML is the most frequent
      type of childhood AML. It is predominantly associated with M2 subtype of AML and
      has unique morphological, immunological prognostic features .

PMID- 15476185
TI  - [Analysis of loss of heterozygosity on chromosome 10 in human prostate carcinoma
      and high grade prostatic intraepithelial neoplasia].
AB  - OBJECTIVE: To detect the status of loss of heterozygosity (LOH) on chromosome 10
      in prostate carcinoma and high grade prostatic intraepithelial neoplasia (PIN).
      METHODS: Pure DNA was obtained from prostate neoplasms and normal tissues by
      tissue microdissection. LOH of chromosome 10 was detected by PCR based
      microsatellite polymorphism analysis technique using 20 pairs of microsatellite
      primers in 16 samples of prostate carcinoma and 14 samples of high grade PIN.
      RESULTS: There were different frequencies of LOH in different loci on chromosome
      10, varying from 0 to 46.2%, mainly located at 10q23 and 10q24-q25 regions. Seven
      samples of high grade PIN had LOH detected on chromosome 10. CONCLUSION: There
      were high frequency of LOH regions on chromosome 10 of prostate carcinoma. The
      rate of LOH in high grade PIN was much lower than that in prostate carcinoma.
      PTEN and MXI1 were two candidate tumor suppressor genes on 10q23 and 10q24-q25.
      They may be potentially involved in the initiation and progression of prostate
      carcinoma.

PMID- 15476186
TI  - [Sequence polymorphism of mtDNA HV1, HV2 overlapping fragments and coding region
      8430-8673nt in Han population of Hebei province].
AB  - OBJECTIVE: To investigate the sequence polymorphism of mtDNA HV1,HV2 overlapping
      fragments and coding region encompassing position 8430-8673 in Hebei Han
      population. METHODS: Polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) combined with sequencing method was used to detect the
      haplotype distribution of mtDNA in 100 Hebei Han individuals. RESULTS: Ninety-one
      haplotypes were noted in 100 unrelated individuals. The gene diversity is 0.9985
      and the random match probability is 0.0115. Compared with the Anderson sequence,
      65 sites of different nucleotide sequences were noted, of which 44 sites were
      previously registered in MITOMAP, 12 sites were not registered and the gene
      mutations were different from MITOMAP at 9 positions. CONCLUSION: The obtained
      data suggest that these loci are valuable genetic markers for personal
      identification and thus could be used as basic data for the forensic application
      of mtDNA in Hebei province.

PMID- 15476187
TI  - [Analysis of HLA-DRB1,DQB1 allele polymorphism in the Kunming Yi nationality
      population].
AB  - OBJECTIVE: To investigate the HLA-DRB1, DQB1 allele polymorphism in Kunming Yi
      nationality population. METHODS: HLA-DRB1, DQB1 DNA types in 70 healthy children
      of Yi nationality in Kunming were analyzed by polymerase chain reaction with
      sequence specific primer (PCR-SSP). RESULTS: Twelve alleles at HLA-DRB1 locus
      were observed in the 70 children: the alleles with gene frequencies higher than
      10% were HLA-DRB1*12(33.57%), DRB1*0901(11.43%), DRB1*04(11.43%); the alleles
      with gene frequencies between 10% and 5% were HLA-DRB1*01(8.57%), DRB1*11(7.86%),
      DRB1*14(7.14%), DRB1*15(7.14%), DRB1*08(5%); the alleles with gene frequencies
      lower than 5% were HLA-DRB1*03(2.86%), DRB1*13(2.14%), DRB1*07(1.43%),
      DRB1*16(1.43%). Seven alleles at HLA-DQB1 locus were observed in the 70 children:
      the alleles with gene frequencies higher than 10% were HLA-DQB1*0301(45%),
      DQB1*05(22.14%), DQB1*0303(12.14%); the alleles with gene frequencies between 10%
      and 5% were HLA-DQB1*04(6.43%), DQB1*06(6.43%); the alleles with gene frequencies
      lower than 5% were HLA-DQB1*0201(4.29%) and DQB1*0302(3.57%). CONCLUSION: The
      distribution of HLA-DRB1, DQB1 allele polymorphism in the Kunming Yi nationality
      population is distinctive. It is neither like that in the South Han population
      nor like that in the North Han population.

PMID- 15476188
TI  - Preliminary investigation of electrodynamic charged droplet processing to couple
      capillary liquid chromatography with matrix-assisted laser desorption/ionization
      mass spectrometry.
AB  - Charged droplet processing methodology, that utilizes electrodynamic levitation
      technology to control the trajectories of picoliter volume charged droplets and
      deliver them to a target plate at atmospheric pressure, has been developed.
      Termed wall-less sample preparation (WaSP), this methodology offers several
      features that could prove beneficial to the preparation of sample spots from
      separation column effluents for matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) analysis. These features include solute pre-concentration
      factors of 10(1) to 10(3) due to volatile solvent evaporation prior to droplet
      deposition onto the target plate, high spatial accuracy of the deposition
      position of each processed droplet (+/-5 microm), and the ability to prepare
      sample spots as small as 20 microm in diameter from a single droplet. Here a new
      mode of operation of this methodology is described and used as an offline post
      column pre-concentrating interface between capillary liquid chromatography
      (capLC) and a target plate for offline MALDI-MS. Using a fraction from the capLC
      separation of peptides produced by the proteolytic digestion of the protein
      cytidine 5'-triphosphate:phosphocholine cytidylyltransferase, MALDI sample spots
      were prepared using the dried-droplet method, direct piezoelectric droplet
      dispensing, and the processing of piezo-dispensed droplets by WaSP. The sample
      spot morphology was investigated using light microscopy, and peptide ion
      abundances produced by MALDI were measured using time-of-flight (TOF) MS. The
      advantages of developing an online capLC/WaSP interface with MALDI-MS in the
      future are discussed along with some of the challenges that may be encountered in
      such an endeavor.

PMID- 15476189
TI  - Cycloreversion and other gas-phase reactions of neutral and cationic pyrrolidine
      fused chlorins and isobacteriochlorins under ion bombardment and electrospray.
AB  - Neutral and cationic pyrrolidine-fused chlorins and isobacteriochlorins derived
      from meso-tetrakis(pentafluorophenyl)porphyrin undergo cycloreversion reactions
      in the gas phase, either when desorbed from a liquid matrix by ion bombardment or
      when electrosprayed. Cycloreversion occurs through loss of either neutral or
      charged moieties, with and without hydrogen and methyl radical migration, and
      both as high- and low-energy collision processes. For the doubly charged
      isobacteriochlorin, one-electron reduction with methyl loss occurs under ion
      bombardment and electrospray, through hypervalent pyrrolidinium radical
      formation.

PMID- 15476191
TI  - Outrunning the bear.

PMID- 15476190
TI  - Design of a conformation-sensitive xenon-binding cavity in the ribose-binding
      protein.

PMID- 15476192
TI  - Cell cycle distribution of CD4+ lymphocytes in HIV-1-infected subjects.
AB  - BACKGROUND: Apoptosis is one of the possible explanations for the progressive
      loss of CD4(+) T lymphocytes in infection with the human immunodeficiency virus
      (HIV), which may interfere with cell cycle distribution. This study evaluated the
      cell cycle of CD4(+) and CD8(+) lymphocytes in HIV-infected subjects and
      controls. METHODS: Two methods to identify lymphocytes for cell cycle analysis
      were evaluated, magnetic beads and concurrent staining, and both were followed by
      propidium iodide DNA labeling. The chosen method was used to evaluate the cell
      cycle of lymphocytes in HIV-1-infected subjects and controls. RESULTS: There was
      no significant difference between the two methods, although a higher variability
      was observed with the magnetic bead cell separation method. A higher proportion
      of cells in the S phase was observed in HIV-1 patients (2.69% vs. 1.19%, P =
      0.016), coupled with a decrease in G(1) (96.11% vs. 98.10%, P = 0.005) in CD4(+)
      lymphocytes, a phenomenon not observed in CD8(+) lymphocytes. No correlation was
      detected between the different cell cycle phases and T-lymphocyte counts or viral
      load. CONCLUSIONS: The present work developed a new approach to evaluate
      lymphocyte cell cycle distribution, applied in the setting of HIV-1 infection. It
      may contribute to the understanding of the CD4(+) T-lymphocytes depletion seen in
      these patients.

PMID- 15476194
TI  - Evaluation of the Salmonella umu test with 83 NTP chemicals.
AB  - There is a need for simple rapid tests for evaluating the carcinogenic potential
      of the thousands of chemical compounds that are developed each year. The DNA
      damaging effects of 83 National Toxicology Program (NTP) chemicals, including
      noncarcinogens and carcinogens, were examined in the umu test by measuring the
      expression of the umuDC-lacZ genes in Salmonella typhimurium TA1535/pSK1002.
      Salmonella were exposed to individual NTP chemicals at 37 degrees C for 2 hr both
      with and without a rat liver S9 mix; the treated cells were then diluted and
      incubated for a further 2 hr (posttreatment assay). O-nitrophenyl-beta-D
      galactoside was added to the cultures and the beta-galactosidase activity driven
      by the Salmonella umuDC-lacZ genes was determined by measurement of the OD(420
      nm) and OD(550 nm) of the cultures. Salmonella cell number was simultaneously
      determined by measurement of OD(600 nm). The overall concordance between
      genotoxicity in the umu test and carcinogenicity was 67%, which was similar to
      the concordance between Ames' test results and carcinogenicity (63%) using the
      same 83 NTP chemicals. The results of this study indicate that the umu test with
      a single Salmonella strain is a simple rapid system, with accuracy comparable to
      existing, more time-consuming assays.

PMID- 15476195
TI  - Environmental biomonitoring using cytogenetic endpoints in a population exposed
      to mercury in the Brazilian Amazon.

PMID- 15476196
TI  - Cyclopenta[cd]fluoranthene and its precursors in combustion exhausts: a survey of
      their bacterial mutagenic activity.
AB  - Cyclopenta[cd]fluoranthene (1) and 3-ethynylfluoranthene (2) have both recently
      been identified in combustion exhausts. In this study, their mutagenic activities
      were compared to that of fluoranthene (3), one of the most abundant polycyclic
      aromatic hydrocarbons (PAHs) in combustion exhausts, in the Salmonella/microsome
      reversion assay (Ames assay) using S. typhimurium strain TA98. The mutagenicity
      of 1 was modest in comparison to other active cyclopenta PAHs. Unexpectedly, 2
      was mutagenic both with and without exogenous metabolic activation (rat liver
      S9). Furthermore, cyclopenta[cd]fluoranthene-3,4-epoxide (6) was synthesized in
      order to evaluate its role as the ultimate mutagenic active form of 1. The
      epoxide 6 was a direct-acting mutagen. In addition, a pyrolysate containing a
      mixture of 1 (85%), 2 (2%), and 3 (13%) obtained by flash vacuum thermolysis of 3
      (1-chloroethenyl)fluoranthene (2a) at 1,050 degrees C was also mutagenic, but a
      significant mutagenic response was detected only in the presence of S9
      activation. The results of this study indicate that 1 and 2 can contribute to the
      mutagenic activity of combustion exhausts.

PMID- 15476197
TI  - Genetic damage detected in CD-1 mouse pups exposed perinatally to 3'-azido-3'
      deoxythymidine or dideoxyinosine via maternal dosing, nursing, and direct gavage:
      II. Effects of the individual agents compared to combination treatment.
AB  - We previously reported extraordinary increases in micronucleated erythrocytes in
      CD-1 mouse pups exposed to 3'-azido-3'-deoxythymidine (AZT) and dideoxyinosine
      (ddI; 50/250, 75/375, 150/750 mg/kg/day AZT/ddI) by gavage throughout gestation
      and lactation, followed by direct pup dosing beginning postnatal day (PND) 4
      (Bishop et al. [2004]: Environ Mol Mutagen 43: 3-9). That study was conducted to
      explore the potential for genetic damage in newborns exposed perinatally to
      antiretrovirals in order to reduce maternal-infant transmission of HIV-1. Because
      dramatic increases in frequencies of micronucleated erythrocytes were seen in
      exposed pups, additional studies were conducted to clarify the relative
      contribution of each drug to the observed damage. Pregnant CD-1 mice were
      administered AZT (50, 75, 150 mg/kg/day) or ddI (250, 375, 750 mg/kg/day) by
      gavage twice daily in equal fractions beginning prior to mating and continuing
      throughout gestation and lactation. Direct pup dosing (same regimens) began on
      PND 4. Peripheral blood erythrocytes of male pups were screened for micronuclei
      on PNDs 1, 4, 8, and 21. Significant increases in micronucleated erythrocytes
      were observed in pups and dams exposed to AZT at all doses and sampling times.
      The highest micronucleus levels were observed in pups on PND 8 after the
      initiation of direct dosing. In contrast, effects seen in pups and dams treated
      with ddI were minimal. These results demonstrate that AZT, a component of many
      anti-HIV combination therapies, induces chromosomal damage in perinatally exposed
      neonatal mice. Comparison of micronucleated cell frequencies induced by AZT alone
      or in combination with ddI suggests that ddI potentiates AZT-induced chromosomal
      damage following direct exposure.

PMID- 15476198
TI  - Response to C. Bosetti et al. (Trends in colorectal cancer mortality in Japan,
      1970-2000).

PMID- 15476199
TI  - Development of a quantitative PCR (TaqMan) assay for relative mitochondrial DNA
      copy number and the common mitochondrial DNA deletion in the rat.
AB  - Changes in mitochondrial DNA copy number and increases in mitochondrial DNA
      mutations, especially deletions, have been associated with exposure to mutagens
      and with aging. Common deletions that are the result of recombination between
      direct repeats in human and rat (4,977 and 4,834, bp, respectively) are known to
      increase in tissues of aged individuals. Previous studies have used long-distance
      PCR and Southern blot or quantitative PCR to determine the frequency of deleted
      mitochondrial DNA. A quantitative PCR (TaqMan) assay was developed to detect both
      mitochondrial DNA copy number and deletion frequency in the rat. This methodology
      allows not only the determination of changes in the amount of mitochondrial DNA
      deletion relative to total mitochondrial DNA but also to determine changes in
      total mitochondrial DNA relative to genomic DNA. As a validation of the assay in
      rat liver, the frequency of the common 4,834 bp deletion is shown to increase
      with age, while the relative mitochondrial DNA copy number rises at a young age
      (3-60 days), then decreases and holds fairly steady to 2 years of age.

PMID- 15476200
TI  - Expression of mitogen-activated protein kinase phosphatase 1, a negative
      regulator of the mitogen-activated protein kinases, in rheumatoid arthritis: up
      regulation by interleukin-1beta and glucocorticoids.
AB  - OBJECTIVE: Mitogen-activated protein kinases (MAPKs) are activated by
      proinflammatory stimuli. MAPK phosphatases (MKPs), in particular MKP-1, have been
      identified as endogenous negative regulators of MAPK activation. Since MAPKs are
      known to be important in rheumatoid arthritis (RA) synoviocyte activation, this
      study assessed the expression, regulation, and function of MKP-1 in RA. METHODS:
      MKP-1 expression was measured by Western blotting (WB) and real-time polymerase
      chain reaction (PCR). RA fibroblast-like synoviocytes (FLS) were treated with
      interleukin-1beta (IL-1beta), tumor necrosis factor alpha, fetal calf serum, and
      dexamethasone. Expression of MAPKs in RA FLS was analyzed by WB using
      phosphospecific antibodies, while IL-6 expression was assessed by real-time PCR.
      RESULTS: MKP-1 protein and messenger RNA were detected in cultured RA FLS. IL
      1beta rapidly up-regulated MKP-1, coinciding with reciprocal down-regulation of
      ERK, JNK, and p38 MAPK phosphorylation. Dexamethasone rapidly and sustainably up
      regulated MKP-1, and this also coincided with down-regulation of ERK, JNK, and
      p38 MAPK phosphorylation. In addition, dexamethasone augmented IL-1beta-induced
      up-regulation of MKP-1, and this was associated with inhibition of ERK, JNK, and
      p38 MAPK phosphorylation and IL-6 expression. Dexamethasone had no effect on the
      phosphorylation of upstream kinases such as MEKK-3/6. In the presence of
      glucocorticoid (GC) receptor antagonist RU 486, the dexamethasone-mediated up
      regulation of MKP-1 was impaired. Moreover, inhibition of MKP-1 expression
      impaired dexamethasone-mediated inhibition of MAPK phosphorylation. CONCLUSION:
      This study demonstrates the expression of MKP-1 in RA FLS. Cytokine and GC
      regulation of MKP-1 may be important in determining the magnitude of the
      inflammatory response in RA that is mediated via MAPKs. The effects of GCs in RA
      may be mediated, in part, via GC receptor-dependent up-regulation of MKP-1.

PMID- 15476201
TI  - Trends in colorectal cancer mortality in Japan, 1970-2000.

PMID- 15476202
TI  - The effect of folic acid and folinic acid supplements on purine metabolism in
      methotrexate-treated rheumatoid arthritis.
AB  - OBJECTIVE: To determine if folinic acid supplementation during methotrexate (MTX)
      therapy for rheumatoid arthritis (RA) reduces both urinary 5-aminoimidazole-4
      carboxamide (AICA) and urinary adenosine excretion more than does folic acid
      supplementation. AICA and adenosine are markers for MTX interference with purine
      metabolism. METHODS: Forty patients with RA who received MTX for 6 weeks were
      randomized to receive either daily folic acid or folinic acid supplements during
      an additional week of MTX therapy. Colorimetric and radioimmunocompetition assays
      were used to measure 24-hour urinary AICA and adenosine excretion levels,
      respectively. RESULTS: At the end of 6 weeks, 24-hour urinary levels of AICA, but
      not adenosine, were elevated as compared with baseline levels (i.e., prior to MTX
      therapy). Folinic acid, but not folic acid, supplementation normalized urinary
      AICA levels during MTX therapy. Relatively high urinary levels of AICA were
      correlated with reduced disease activity. No similar correlations were seen with
      urinary adenosine levels. CONCLUSION: The blockade of purine nucleotide
      biosynthesis by MTX at the AICA ribonucleotide transformylase-catalyzed step may
      be related to the efficacy of MTX, and this blockade is effectively relieved by
      folinic acid, but not by folic acid, supplementation.

PMID- 15476203
TI  - Association of increased expression of macrophage elastase (matrix
      metalloproteinase 12) with rheumatoid arthritis.
AB  - OBJECTIVE: Increased enzymatic activity of matrix metalloproteinases (MMPs) may
      promote the progression of rheumatoid arthritis (RA). We undertook this study to
      investigate the expression and localization of human macrophage elastase (MMP-12)
      in synovial tissue from RA patients and to compare MMP-12 levels in the synovial
      tissue and synovial fluid of RA patients with the corresponding levels in
      patients with osteoarthritis (OA). METHODS: We obtained synovial tissues from 23
      RA patients and 29 OA patients and analyzed MMP-12 expression using
      immunohistochemistry, Western and Northern blotting analyses, and zymography.
      Furthermore, we quantified MMP-12 levels in synovial fluid by Western blotting
      and zymography. RESULTS: Northern blotting analysis demonstrated that RA synovial
      tissue contained higher levels of MMP-12 messenger RNA than did OA synovial
      tissue. Western blotting revealed that MMP-12 proteins were consistently and
      markedly increased in RA synovial tissue compared with OA synovial tissue. A
      greater amount of immunoreactive proteins corresponding to catalytic forms of MMP
      12 was present in RA synovial tissue and synovial fluid, and the MMP-12 proteins
      exhibited caseinolytic activity in vitro. Immunohistochemical staining showed
      that the major cells expressing MMP-12 were synovial lining cells, many of which
      were inflammatory macrophages. CONCLUSION: These results establish a possible
      mechanism by which macrophage-derived MMP-12 may play an important role in the
      destructive process in RA. Inhibition of MMP-12 may be a potential modality for
      the treatment of RA.

PMID- 15476204
TI  - A gene-environment interaction between smoking and shared epitope genes in HLA-DR
      provides a high risk of seropositive rheumatoid arthritis.
AB  - OBJECTIVE: The main genetic risk factor for rheumatoid arthritis (RA) is the
      shared epitope (SE) of HLA-DR, while smoking is an important environmental risk
      factor. We studied a potential gene-environment interaction between SE genes and
      smoking in the etiology of the 2 major subgroups of RA: rheumatoid factor (RF)
      seropositive and RF-seronegative disease. METHODS: A population-based case
      control study involving incident cases of RF-seropositive and RF-seronegative RA
      (858 cases and 1,048 controls) was performed in Sweden. Cases and controls were
      classified according to their cigarette smoking status and HLA-DRB1 genotypes.
      The relative risk of developing RA was calculated for different gene/smoking
      combinations and was compared with the relative risk in never smokers without SE
      genes. RESULTS: The relative risk of RF-seropositive RA was 2.8 (95% confidence
      interval [95% CI] 1.6-4.8) in never smokers with SE genes, 2.4 (95% CI 1.3-4.6)
      in current smokers without SE genes, and 7.5 (95% CI 4.2-13.1) in current smokers
      with SE genes. Smokers carrying double SE genes displayed a relative risk of RF
      seropositive RA of 15.7 (95% CI 7.2-34.2). The interaction between smoking and SE
      genes was significant, as measured by the attributable proportion due to
      interaction, which was 0.4 (95% CI 0.2-0.7) for smoking and any SE, and 0.6 (95%
      CI 0.4-0.9) for smoking and a double SE. Neither smoking nor SE genes nor the
      combination of these factors increased the risk of developing RF-seronegative RA.
      CONCLUSION: The disease risk of RF-seropositive RA associated with one of the
      classic genetic risk factors for immune-mediated diseases (the SE of HLA-DR) is
      strongly influenced by the presence of an environmental factor (smoking) in the
      population at risk.

PMID- 15476205
TI  - Interaction between RANKL and HLA-DRB1 genotypes may contribute to younger age at
      onset of seropositive rheumatoid arthritis in an inception cohort.
AB  - OBJECTIVE: To determine whether the RANKL and HLA-DRB1 "shared epitope" (SE)
      genotypes contribute to the development of rheumatoid arthritis (RA). METHODS: We
      studied 237 patients with early RA (within 15 months of symptom onset) who were
      seropositive for rheumatoid factor. HLA-DRB1 genotyping was performed using the
      polymerase chain reaction (PCR)-based oligonucleotide probe assay. RANKL
      polymorphisms were analyzed using PCR pyrosequencing for SNP1 and fluorescence
      based PCR for the presence or absence of the TAAA insertion. RESULTS: The
      presence of SE-containing DRB1*04 alleles was associated with an earlier age at
      RA onset (mean +/- SD 47 +/- 12.7 years versus 53 +/- 12.5 years in SE- patients;
      P = 0.0004). The 2 novel RANKL polymorphisms were in strong linkage
      disequilibrium (P < 0.0001) and were associated with earlier ages at disease
      onset (e.g., for the CC versus CT/TT genotypes, 44 +/- 13.5 years versus 51 +/-
      12.7 years; P = 0.0080). The mean age at disease onset in SE+ patients with the
      RANKL-CC genotype (35 +/- 7.2 years) was a mean of 18 years younger than in SE-
      patients with RANKL-CT/TT (53 +/- 12.5 years; P < 0.0001) and was 17 years
      younger than in SE- patients with RANKL-CC (52 +/- 13.2 years; P = 0.0005). The
      proportion of patients with both the SE and RANKL risk alleles was highest (23%)
      in those who developed RA during their third decade of life (ages 20-30 years),
      with a declining trend among those who developed RA during their fourth (16%),
      fifth (5%), and sixth or later (0%) decades. Interestingly, 92% of the patients
      diagnosed as having RA between ages 20 and 30 years carried at least 1 of the RA
      associated DRB1*04 alleles, suggesting a strong influence of the SE in the early
      onset of RA. The majority of patients who developed RA symptoms in their third to
      fifth decades (74 of 119 [62%]) carried at least 1 copy of the DRB1*04 alleles;
      in contrast, fewer than half of the patients who developed RA in their sixth
      decade or later (50 of 118 [42%]) had DRB1*04 alleles. RANKL genotypes were not
      associated with erosive disease at baseline or with the yearly progression rate
      of radiographic joint damage. CONCLUSION: This study provides the first evidence
      that novel RANKL polymorphisms were associated with an earlier age at RA onset in
      SE+, but not SE-, patients and that an interaction between SE-containing HLA-DRB1
      and RANKL polymorphisms increased the disease penetrance, resulting in a mean age
      at RA onset that was 18-20 years younger. Our results also suggested genetic
      differences between patients with early-onset and those with late-onset RA.

PMID- 15476206
TI  - Flow cytometric detection of complement-activating HLA antibodies.
AB  - BACKGROUND: Antibodies to HLA are implicated in allograft rejection; as a
      consequence, tests to identify them are indicated in organ transplantation. Flow
      cytometry (FC) may improve the outcome of organ transplantation. Although
      increasingly used, most of the available FC techniques do not discriminate
      between complement and noncomplement-activating antibodies. However, the clinical
      relevance of noncomplement-activating antibodies is controversial. Therefore,
      many laboratories still use the conventional complement-dependent
      microlymphocytotoxicity crossmatch (CDC-XM) alone or in combination with FC.
      METHODS: We describe a novel flow cytometric complement-dependent cytotoxicity
      crossmatch assay (FC-CDC-XM) that clearly identifies complement-binding HLA
      antibodies. With the aid of a three-color FACScan flow cytometer with a standard
      argon ion laser, we used fluorescence-conjugated anti-CD3 for the identification
      of T lymphocytes, anti-CD19 antibodies for the identification of B lymphocytes,
      and propidium iodide (PI) for the identification of damaged cells. Fluorescence
      conjugated anti-CD3 and anti-CD19 antibodies were detected in the green (FL1) and
      orange (FL2) ranges of the spectrum. PI fluorescence was measured with the red
      (FL3) fluorescence channel. Gating of lymphocytes was performed using side
      scatter versus FL1 or FL2 dot plots for the identification of T and B
      lymphocytes, respectively. RESULTS: FC-CDC-XM was able to correctly identify all
      antibodies tested as specific to HLA class I (n = 18) or II (n = 4). CONCLUSIONS:
      The new FC-CDC-XM is more sensitive and more objective than the standard CDC-XM
      and can be used for pre- and posttransplant diagnoses and for the detection of
      other antibody-mediated cytotoxic reactions.

PMID- 15476207
TI  - Determinants of cysteine pKa values in creatine kinase and alpha1-antitrypsin.
AB  - The structural determinants of the unusually low pK(a) values of Cys282 in human
      creatine kinase and Cys232 in alpha1-antitrypsin were studied computationally. We
      have demonstrated that hydrogen bonding to the cysteine residue is the prime
      determinant for both proteins. In the case of creatine kinase, the hydrogen bond
      donors are a serine side chain and an amide NH-group, while in alpha1-antitrypsin
      the donor is an amide NH. Each hydrogen bond lowers the pK(a) by between 0.8 and
      1.5 pH units. The 1.1-unit lowering due to the Ser284-Cys282 hydrogen bond is in
      good agreement with the 1.2-unit difference between the Cys282 pK(a) value of
      wild-type and the S284A mutant of creatine kinase.

PMID- 15476208
TI  - Sequence patterns associated with disordered regions in proteins.
AB  - The relationship between amino acid sequence and intrinsic disorder in proteins
      is investigated. Two databases, one of disordered proteins and the other of
      globular proteins, are analyzed and compared in order to extract simple sequence
      patterns of a few amino acids or amino acid properties that characterize
      disordered segments. It is found that a number of reliable, nonrandom
      associations exists. In particular, two types of patterns appear to be recurrent:
      a proline-rich pattern and a (positively or negatively) charged pattern. These
      results indicate that local sequence information can determine disordered regions
      in proteins. The derived patterns provide some insights into the physical reasons
      for disordered structures. They should also be helpful in improving currently
      available prediction methods.

PMID- 15476209
TI  - Fibrinogen receptor antagonists induce conformational changes of the human
      platelet glycoprotein IIb.
AB  - BACKGROUND: Controversial results have been reported concerning the ability of
      fibrinogen receptor antagonists (fibans) to induce conformational changes in the
      fibrinogen receptor after binding to it as the initial step of fibrinogen binding
      and platelet activation. METHODS: Platelets in citrated whole blood were stained
      with several pairs of anti-glycoprotein (anti-GP) IIb-directed monoclonal
      antibodies conjugated to phycoerythrin (PE) or indirectly labeled with Cy5. Pairs
      of monoclonal antibodies that induced a high-fluorescence resonance energy
      transfer (FRET) efficiency served as tools to detect activation-dependent changes
      of GP IIb after addition of adenosine diphosphate and several fibans. RESULTS:
      Using the combination of the clones 5B12-PE and P2-biotin/SA-Cy5, a concentration
      dependent alteration of the GP IIb conformation was observed after addition of
      tirofiban, eptifibatide, and lotrafiban. Magnitude and kinetics differed among
      the investigated substances. CONCLUSION: The newly developed FRET assay allows
      the direct investigation of conformational changes of GP IIb after addition of
      platelet agonists or receptor ligands, as shown for three fibans.

PMID- 15476210
TI  - Relationship of radiographic progression to the pathogenic mechanism of
      rheumatoid arthritis: comment on the article by Molenaar et al.

PMID- 15476211
TI  - Enzyme classification by ligand binding.
AB  - The problem of assigning a biochemical function to newly discovered proteins has
      been traditionally approached by expert enzymological analysis, sequence
      analysis, and structural modeling. In recent years, the appearance of databases
      containing protein-ligand interaction data for large numbers of protein classes
      and chemical compounds have provided new ways of investigating proteins for which
      the biochemical function is not completely understood. In this work, we introduce
      a method that utilizes ligand-binding data for functional classification of
      enzymes. The method makes use of the existing Enzyme Commission (EC)
      classification scheme and the data on interactions of small molecules with
      enzymes from the BRENDA database. A set of ligands that binds to an enzyme with
      unknown biochemical function serves as a query to search a protein-ligand
      interaction database for enzyme classes that are known to interact with a similar
      set of ligands. These classes provide hypotheses of the query enzyme's function
      and complement other computational annotations that take advantage of sequence
      and structural information. Similarity between sets of ligands is computed using
      point set similarity measures based upon similarity between individual compounds.
      We present the statistics of classification of the enzymes in the database by a
      cross-validation procedure and illustrate the application of the method on
      several examples.

PMID- 15476212
TI  - Multisequence magnetic resonance imaging study of neuropsychiatric systemic lupus
      erythematosus.
AB  - OBJECTIVE: To investigate the relationship between magnetization transfer imaging
      (MTI), diffusion-weighted imaging (DWI), proton magnetic resonance spectroscopy
      (H-MRS), and T2 relaxometry findings in patients with primary neuropsychiatric
      systemic lupus erythematosus (NPSLE). METHODS: The study group consisted of 24
      female patients (mean age 36 years [range 23-65]) who had had a variety of
      neuropsychiatric symptoms that were judged to be due to NPSLE according to the
      criteria of the American College of Rheumatology. Patients with current active
      disease were excluded from participation. Quantitative MTI, DWI, H-MRS, and T2
      relaxometry data were acquired in all patients, and the correlation coefficients
      were calculated. RESULTS: MTI results reflecting a decrease in homogeneity of
      cerebral parenchyma correlated significantly with H-MRS results representing
      axonal damage. MTI results also correlated significantly with DWI results
      reflecting increased diffusivity in the cerebral parenchyma. Finally, MTI results
      reflecting decreased cerebral homogeneity correlated significantly with increased
      T2 relaxation time, associated with either edema or gliosis. Increased T2
      relaxation time correlated significantly with DWI results reflecting increased
      diffusivity. With the exception of the correlation between H-MRS and MTI
      findings, there was no significant correlation between H-MRS results and any
      other parameter. CONCLUSION: The selected study parameters represent different
      biologic features in the human brain and can be informative with regard to
      different pathologic processes in NPSLE. The demonstrated associations between
      MTI, DWI, H-MRS, and T2 data in patients with a history of NPSLE suggest that
      there is one pathogenesis and/or common neuropathologic outcome in NPSLE despite
      differences in clinical presentation.

PMID- 15476213
TI  - Development and validation of the health assessment questionnaire II: a revised
      version of the health assessment questionnaire.
AB  - OBJECTIVE: The Health Assessment Questionnaire (HAQ) has become the most common
      tool for measuring functional status in rheumatology. However, the HAQ is long
      (34 questions, including 20 concerning activities of daily living and 14 relating
      to the use of aids and devices) and somewhat burdensome to score, has some floor
      effects, and has psychometric problems relating to linearity and confusing items.
      We undertook this study to develop and validate a revised version of the HAQ (the
      HAQ-II). METHODS: Using Rasch analysis and a 31-question item bank, including 20
      HAQ items, the 10-item HAQ-II was developed. Five original items from the HAQ
      were retained. We studied the HAQ-II in 14,038 patients with rheumatic disease
      over a 2-year period to determine its validity and reliability. RESULTS: The HAQ
      II was reliable (reliability of 0.88, compared with 0.83 for the HAQ), measured
      disability over a longer scale than the HAQ, and had no nonfitting items and no
      gaps. Compared with the HAQ, modified HAQ, and Medical Outcomes Study Short Form
      36 physical function scale, the HAQ-II was as well correlated or better
      correlated with clinical and outcome variables. The HAQ-II performed as well as
      the HAQ in a clinical trial and in prediction of mortality and work disability.
      The mean difference between the HAQ and HAQ-II scores was 0.02 units. CONCLUSION:
      The HAQ-II is a reliable and valid 10-item questionnaire that performs at least
      as well as the HAQ and is simpler to administer and score. Conversion from HAQ to
      HAQ-II and from HAQ-II to HAQ for research purposes is simple and reliable. The
      HAQ-II can be used in all places where the HAQ is now used, and it may prove to
      be easier to use in the clinic.

PMID- 15476214
TI  - Large vessel compromise in antineutrophil cytoplasmic antibody-associated
      systemic vasculitis: comment on the article by Booth et al.

PMID- 15476215
TI  - Outcomes of hospitalizations for myocardial infarctions and cerebrovascular
      accidents in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have increased risks
      of acute myocardial infarction (AMI) and cerebrovascular accident (CVA), but it
      is not known whether they have worse outcomes after AMI or CVA compared with
      patients without SLE. This study compared in-hospital mortality, length of stay,
      and other measures of severity (congestive heart failure or need for coronary
      artery bypass grafting after AMI; discharge to a skilled nursing facility after
      CVA) between patients with SLE and patients without SLE who were hospitalized for
      AMI or CVA. METHODS: Data on all patients hospitalized in California with either
      AMI or CVA from 1996 to 2000 were abstracted from a state hospitalization
      database. Outcomes after AMI were compared between 519 patients with SLE and
      214,771 patients without SLE, and outcomes after CVA were compared between 905
      patients with SLE and 293,326 patients without SLE. Analyses were performed
      separately for men and women. RESULTS: Among women with AMI, there were no
      differences in the risk of in-hospital mortality, long length of stay, or
      congestive heart failure between patients with SLE and those without SLE, but
      women with SLE were less likely to undergo coronary artery bypass grafting.
      Outcomes after AMI did not differ between men with SLE and men without SLE. Among
      women with CVA, there were no differences in outcomes between patients with SLE
      and patients without SLE. Men with SLE were almost twice as likely to have a long
      length of stay after CVA than were men without SLE. CONCLUSION: Outcomes after
      AMI and CVA are generally similar between patients with SLE and those without
      SLE.

PMID- 15476216
TI  - Regulation of the symmetry and intensity of immune complex-mediated synovitis by
      nuclear factor of activated T cells.

PMID- 15476218
TI  - Matrix metalloproteinase 12-dependent cleavage of urokinase receptor in systemic
      sclerosis microvascular endothelial cells results in impaired angiogenesis.
AB  - OBJECTIVE: Defective angiogenesis, resulting in tissue ischemia, is particularly
      prominent in the diffuse form of systemic sclerosis (SSc). The present study was
      undertaken to identify possible differences between normal and SSc microvascular
      endothelial cells (MVECs) in the expression of the cell-associated urokinase-type
      plasminogen activator (uPA)/uPA receptor (uPAR) system, which is critical in the
      angiogenic process. METHODS: MVECs were isolated from the dermis of healthy
      individuals and from the dermis of patients with diffuse SSc. The uPA/uPAR system
      was examined at the protein and messenger RNA levels. Angiogenesis was assayed on
      Matrigel-coated porous filters and plates to evaluate cell proliferation,
      invasion, and capillary morphogenesis. Cleavage of uPAR and the activity of
      matrix metalloproteinase 12 (MMP-12) were evaluated by Western blotting. RESULTS:
      Compared with MVECs from healthy skin, MVECs from SSc patients showed higher
      expression of uPAR. However, in SSc MVECs, uPAR undergoes truncation between
      domain 1 and domain 2, as shown by flow cytometry, enzyme-linked immunosorbent
      assay, and Western blotting, a cleavage that is known to impair uPAR functions.
      These properties of SSc MVECs were associated with poor spontaneous and uPA
      dependent invasion, proliferation, and capillary morphogenesis. The uPAR cleavage
      occurring in SSc MVECs was associated with overexpression of MMP-12. SSc MVEC
      conditioned medium impaired uPA-dependent proliferation and invasion as well as
      capillary morphogenesis in normal MVECs in vitro. Both a general hydroxamate
      inhibitor of MMP activity and anti-MMP-12 antibodies restored this SSc MVEC
      induced impaired functioning. CONCLUSION: Overproduction of MMP-12 by SSc MVECs
      accounts for the cleavage of uPAR and the impairment of angiogenesis in vitro and
      may contribute to reduced angiogenesis in SSc patients.

PMID- 15476219
TI  - Combined effects of an anticoagulant and a lipid-lowering agent on the prevention
      of steroid-induced osteonecrosis in rabbits.
AB  - OBJECTIVE: To investigate the effects of combination treatment with an
      anticoagulant (warfarin) plus a lipid-lowering agent (probucol) on the prevention
      of steroid-induced osteonecrosis (ON) in rabbits. METHODS: Adult male Japanese
      white rabbits were injected once intramuscularly with 20 mg/kg of
      methylprednisolone acetate into the right gluteus medius muscle. The rabbits were
      then divided into 4 groups and treated as follows: one group received warfarin
      plus probucol (WP; n = 25), one received probucol alone (PA; n = 30), one
      received warfarin alone (WA; n = 26), and one received no treatment
      (nonprophylactic [NP]; n = 20). Two weeks after the steroid injection, the femora
      and humeri were examined histopathologically for the presence of ON. The sizes of
      the bone marrow fat cells were examined morphologically. Hematologic examinations
      were performed before and after the steroid injection. RESULTS: The incidence of
      ON in the WP group (5%) was significantly lower than that observed in the NP
      group (70%). While the incidence rates of ON in the PA (38%) and WA (33%) groups
      were also significantly lower than that in the NP group, they were significantly
      higher than that observed in the WP group. The sizes of the bone marrow fat cells
      in both the WP (53.5 +/- 4.1 microm) and the PA (52.0 +/- 5.0 microm) groups were
      significantly smaller than those in the NP group (60.0 +/- 4.0 microm). We also
      observed a prolongation of the prothrombin time and a reduction in the plasma
      lipid levels in the WP group during the study. CONCLUSION: This study
      experimentally confirmed that the combined use of an anticoagulant and a lipid
      lowering agent helps prevent steroid-induced ON in rabbits.

PMID- 15476220
TI  - Histone deacetylase inhibitor suppression of autoantibody-mediated arthritis in
      mice via regulation of p16INK4a and p21(WAF1/Cip1) expression.
AB  - OBJECTIVE: To examine whether depsipeptide (FK228), a histone deacetylase (HDA)
      inhibitor, has inhibitory effects on the proliferation of synovial fibroblasts
      from rheumatoid arthritis (RA) patients, and to examine the effects of systemic
      administration of FK228 in an animal model of arthritis. METHODS: Autoantibody
      mediated arthritis (AMA) was induced in 19 male DBA/1 mice (6-7 weeks old); 10 of
      them were treated by intravenous administration of FK228 (2.5 mg/kg), and 9 were
      used as controls. The effects of FK228 were examined by radiographic, histologic,
      and immunohistochemical analyses and arthritis scores. RA synovial fibroblasts
      (RASFs) were obtained at the time of joint replacement surgery. In vitro effects
      of FK228 on cell proliferation were assessed by MTT assay. Cell morphology was
      examined by light and transmission electron microscopy. The effects on the
      expression of the cell cycle regulators p16INK4a and p21(WAF1/Cip1) were examined
      by real-time polymerase chain reaction and Western blot analysis. The acetylation
      status of the promoter regions of p16INK4a and p21(WAF1/Cip1) were determined by
      chromatin immunoprecipitation assay. RESULTS: A single intravenous injection of
      FK228 (2.5 mg/ml) successfully inhibited joint swelling, synovial inflammation,
      and subsequent bone and cartilage destruction in mice with AMA. FK228 treatment
      induced histone hyperacetylation in the synovial cells and decreased the levels
      of tumor necrosis factor alpha and interleukin-1beta in the synovial tissues of
      mice with AMA. FK228 inhibited the in vitro proliferation of RASFs in a dose
      dependent manner. Treatment of cells with FK228 induced the expression of
      p16INK4a and up-regulated the expression of p21(WAF1/Cip1). These effects of
      FK228 on p16INK4a and p21(WAF1/Cip1) were related to the acetylation of the
      promoter region of the genes. CONCLUSION: Our findings strongly suggest that
      systemic administration of HDA inhibitors may represent a novel therapeutic
      target in RA by means of cell cycle arrest in RASFs via induction of p16INK4a
      expression and increase in p21(WAF1/Cip1) expression.

PMID- 15476221
TI  - Interferon-alpha-inducible proteins are novel autoantigens in murine lupus.
AB  - OBJECTIVE: To investigate the spectrum of B cell autoimmunity in the recently
      described anti-CD1-autoreactive T cell receptor (TCR)-transgenic murine lupus
      like (CD1 lupus-like) model. METHODS: Lethally irradiated BALB/c/nu/nu mice were
      injected intravenously with donor BALB/c bone marrow and spleen cells expressing
      TCRalpha and TCRbeta transgenes that recognize CD1d. Sera from adoptive host
      animals that developed lupus (i.e., CD1 lupus mice) were collected at serial time
      points and analyzed by Western blotting and immunoprecipitation, using protein
      extracts prepared from NIH3T3 mouse fibroblasts and EL-4 lymphocytes,
      respectively. Sera obtained from older animals in several models of spontaneous
      lupus (NZB/NZW, MRL++, and MRL/lpr mice), unmanipulated BALB/c/nu/nu mice, and
      normal BALB/c mice were used as controls. RESULTS: Analyses demonstrated that the
      prominent targets of autoantibodies in the CD1 lupus-like model are interferon
      alpha (IFNalpha)-inducible antigens. Biochemical and serologic characterizations
      identified one antigen as belonging to the interferon-inducible 202 (Ifi202)
      subfamily of proteins within the Ifi200 family, and a second antigen as a member
      of the 70-kd heat-shock protein family. Autoantibodies directed against these
      antigens were rapidly produced at an early stage of disease. Anti-p50
      autoantibodies were present in sera from 7 (78%) of 9 CD1 lupus mice that
      developed severe kidney disease. CONCLUSION: IFNalpha-inducible proteins
      represent a novel class of autoantigens in murine lupus, and the findings suggest
      additional roles for IFNalpha in this disease. Since Ifi202 autoantigens are
      encoded by the murine non-major histocompatibility complex lupus-susceptibility
      gene locus Ifi202, these data provide a link between recent advances in lupus
      genetics and the formation of autoantibodies.

PMID- 15476222
TI  - Safety and efficacy of tumor necrosis factor alpha blockade in systemic lupus
      erythematosus: an open-label study.
AB  - OBJECTIVE: To investigate the safety of therapeutic tumor necrosis factor alpha
      (TNFalpha) blockade in patients with systemic lupus erythematosus (SLE), in whom
      this proinflammatory cytokine is significantly increased and may be involved in
      the disease pathogenesis. METHODS: In an open-label study, 6 patients with
      moderately active SLE (4 with nephritis and 3 with arthritis refractory to other
      therapies) were given 4 300-mg doses of infliximab, a chimeric anti-TNFalpha
      antibody, in addition to immunosuppression with azathioprine or methotrexate.
      RESULTS: The only significant adverse events observed were urinary tract
      infection in 3 patients, 1 of which was accompanied by Escherichia coli
      bacteremia, and a prolonged febrile episode of putatively viral origin in 1 of
      them. These patients had similar infectious conditions in the past. In none of
      the patients was it necessary to terminate the treatment prematurely. Levels of
      antibodies to double-stranded DNA and cardiolipin increased in 4 patients each,
      but this was not associated with a decrease in serum complement levels, with
      vascular events, or with flares. In contrast, disease activity declined during
      therapy. All 3 patients with joint involvement experienced remission of
      arthritis, which relapsed 8-11 weeks after the last infliximab infusion. In the 4
      patients with lupus nephritis, proteinuria decreased significantly within 1 week
      after initiation of therapy and was diminished by > or = 60% within 8 weeks,
      remaining at low levels until the end of the observation period (at least several
      months). CONCLUSION: Infliximab did not lead to adverse events related to an
      increase in SLE activity, although autoantibodies to double-stranded DNA and
      cardiolipin increased, as expected. This finding, coupled with the clinical
      improvement in the inflammatory manifestations of the disease, indicates that
      further study in larger controlled trials is warranted.

PMID- 15476223
TI  - Outcome of pregnancies in patients with anti-SSA/Ro antibodies: a study of 165
      pregnancies, with special focus on electrocardiographic variations in the
      children and comparison with a control group.
AB  - OBJECTIVE: Aside from congenital heart block (CHB), sinus bradycardia and
      prolongation of the corrected QT (QTc) interval have been reported in infants
      born to mothers with anti-SSA antibodies. To assess the pathologic nature of
      these manifestations, this study focused on electrocardiographic (EKG) variations
      in these children, comparing them with findings in a control group. METHODS: We
      studied 165 consecutive pregnancies in 106 anti-SSA-positive women with
      connective tissue diseases (CTDs). EKGs obtained on 58 children of this group
      were compared with those obtained on 85 infants born to mothers with CTD who were
      negative for both anti-SSA and anti-SSB. RESULTS: No statistically significant
      difference was seen between the 2 study groups with regard to gestational age,
      prematurity, birth weight, age of the children at the time of EKG, age of the
      mothers, or treatments received by the mothers during their pregnancies. Seven of
      137 children developed cutaneous neonatal lupus syndrome; 1 child developed CHB
      (CHB risk of 1 in 99 [1%] if only the first prospectively observed pregnancy in
      women without a history of CHB is included in the analysis). For EKGs recorded
      during the first 2 months of life, the mean +/- SD PR interval was 96 +/- 16 msec
      in the anti-SSA-positive group and 96 +/- 13 msec in the anti-SSA-negative group
      (P = 0.84), with mean QTc values of 397 +/- 27 and 395 +/- 25 msec (P = 0.57) and
      mean heart rates of 141 +/- 23 and 137 +/- 21 beats per minute (P = 0.20),
      respectively. No difference in the PR interval, QTc interval, or heart rate was
      observed for EKGs obtained between 2 and 4 months of life. When EKGs obtained at
      0-2 months were compared with those obtained at 2-4 months, a physiologic
      prolongation of the QTc interval was observed in both study groups. No sudden
      infant death or symptomatic arrhythmia occurred during the first year of life.
      CONCLUSION: The EKG findings in children of anti-SSA-positive and anti-SSA
      negative mothers were not significantly different. Our results suggest that the
      prolongation of the QTc interval and sinus bradycardia that have recently been
      reported in children of mothers with anti-SSA antibodies occur independently of
      the anti-SSA antibodies. The pathologic nature of these EKG variations was not
      confirmed by our controlled study.

PMID- 15476225
TI  - A six-month followup of a randomized trial comparing the efficacy of a lateral
      wedge insole with subtalar strapping and an in-shoe lateral-wedge insole in
      patients with varus deformity osteoarthritis of the knee.
AB  - OBJECTIVE: To assess the effect of a lateral-wedge insole with elastic strapping
      of the subtalar joint on the femorotibial angle in patients with varus deformity
      of the knee. METHODS: The efficacy of a wedged insole with subtalar straps and
      that of a traditional wedged insole shoe insert were compared. Sixty-six female
      outpatients with knee osteoarthritis (OA) were randomized (according to birth
      date) to be treated with either the strapped or the traditional inserted insole.
      Standing radiographs with unilateral insole use were used to analyze the
      femorotibial angles for each patient. In both groups, the baseline and 6-month
      visual analog scale (VAS) scores for subjective knee pain and the Lequesne index
      scores for knee OA were compared. RESULTS: The 61 patients who completed the 6
      month study were evaluated. At baseline, there was no significant difference in
      the femorotibial angle (P = 0.66) and the VAS score (P = 0.75) between the 2
      groups. At the 6-month assessment, the 29 subjects wearing the subtalar-strapped
      insole demonstrated a significantly decreased femorotibial angle (P < 0.0001) and
      significantly improved VAS scores (P = 0.001) and Lequesne index scores (P =
      0.033) compared with their baseline assessments. These significant differences
      were not observed in the 32 subjects assigned to the traditional shoe-inserted
      wedged insole. CONCLUSION: These results suggest that an insole with a subtalar
      strap maintained the valgus correction of the femorotibial angle in patients with
      varus knee OA for 6 months, indicating longer-term clinical improvement with the
      strapped insert compared with the traditional insert.

PMID- 15476226
TI  - Characterization of pristane-induced arthritis, a murine model of chronic
      disease: response to antirheumatic agents, expression of joint cytokines, and
      immunopathology.
AB  - OBJECTIVE: To characterize chronic murine pristane-induced arthritis (PIA) with
      regard to the response to antirheumatic agents, expression levels of
      proinflammatory cytokines, and immunopathologic features. METHODS: Male DBA/1
      mice were injected intraperitoneally with pristane oil to induce a chronic
      polyarthritis, which was monitored by visual scoring. Serum antibody and
      splenocyte responses to a panel of putative joint-derived autoantigens were
      measured. Whole paws were evaluated postmortem for changes in the levels of
      proinflammatory cytokines tumor necrosis factor alpha (TNFalpha), interleukin
      1beta (IL-1beta), and IL-6 by enzyme-linked immunosorbent assay, and standard
      histopathology techniques were used to determine joint structural changes.
      Therapeutic studies were performed for up to 8 weeks of dosing with prednisolone,
      methotrexate, 3 nonsteroidal antiinflammatory drugs (celecoxib, diclofenac, and
      indomethacin), a p38 MAPK inhibitor, SB242235, and human soluble TNF receptor
      (sTNFR; etanercept) and murine sTNFR fusion proteins. RESULTS: Antibody and
      cellular responses to the putative joint autoantigens revealed a broad extent of
      autoimmunity in PIA. TNFalpha, IL-1beta, and IL-6 were all persistently up
      regulated in PIA joints. Prednisolone, methotrexate, celecoxib, indomethacin, and
      SB242235 all significantly reduced the arthritis scores. Etanercept was
      ineffective in reducing the arthritis scores, whereas murine sTNFR produced a
      significant, but nonsustained, benefit. Only prednisolone significantly reduced
      the expression of TNFalpha, IL-1beta, and IL-6 in the joints. Prednisolone and
      methotrexate demonstrated the most effective joint protection. CONCLUSION: We
      have markedly extended the characterization of PIA as a murine model of chronic
      inflammatory arthritis by demonstrating cellular and humoral autoantigenicity,
      elevation of clinically precedented joint cytokines, and variation in the
      response to several antirheumatic therapies. PIA offers significant potential for
      the long-term study of immunopathologic mechanisms and novel therapies in
      rheumatoid arthritis.

PMID- 15476227
TI  - Radiologic progression and clinical remission in rheumatoid arthritis: comment on
      the article by Molenaar et al.

PMID- 15476228
TI  - Reduction of synovial sublining layer inflammation and proinflammatory cytokine
      expression in psoriatic arthritis treated with methotrexate.
AB  - OBJECTIVE: Methotrexate is one of the most commonly used disease-modifying
      antirheumatic drugs in the management of psoriatic arthritis (PsA). Despite the
      differences between the inflammation in PsA and rheumatoid arthritis (RA), the
      effects of methotrexate on the synovium have been described solely in RA. In this
      study, we sought to determine the effects of methotrexate on the inflammatory
      infiltrate and on cytokine and metalloproteinase gene expression in the synovium
      of PsA patients. METHODS: Ten patients with PsA (median duration 18 months)
      underwent arthroscopy and synovial biopsy of an inflamed knee before and after
      clinical improvement induced by methotrexate. Immunohistologic analysis was
      performed using antibodies to CD3, CD4, CD8, CD68, factor VIII, vascular cell
      adhesion molecule, E-selectin, and intercellular adhesion molecule (ICAM). Matrix
      metalloproteinase 3 (MMP-3) and tissue inhibitor of metalloproteinases 1 (TIMP-1)
      messenger RNA (mRNA) were quantified by competitive reverse transcription
      polymerase chain reaction (RT-PCR). Interleukin-1alpha (IL-1alpha), IL-1beta, IL
      2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, interferon-gamma
      (IFNgamma), and tumor necrosis factor alpha (TNFalpha) mRNA expression was
      quantified by real-time PCR. RESULTS: Patients received a median methotrexate
      dosage of 13.75 mg/week (range 7.5-15) for a median of 11.5 months (range 7-14
      months). The Ritchie Articular Index, swollen joint count, and Disease Activity
      Score were significantly reduced. There was a decrease in all immunohistologic
      staining, although this was statistically significant only for CD3, CD4, CD8,
      CD68, E-selectin, and ICAM. Despite clinical improvement in all patients, there
      was a residual T cell infiltrate in all synovial biopsy tissues. The synovial
      lining layer thickness, but not hypervascularity, was significantly reduced.
      There was also a significant reduction in MMP-3, but not TIMP-1, expression.
      Before treatment, PsA synovium was characterized by a predominant expression of
      the proinflammatory cytokines IL-15, IFNgamma, IL-1beta, and TNFalpha and the
      antiinflammatory cytokine IL-10. Methotrexate reduced synovial IL-1alpha, IL
      1beta, IL-8, IL-10, IL-15, IFNgamma, and TNFalpha mRNA expression, but the effect
      was significant only for IL-8. CONCLUSION: Methotrexate produced a clinical
      response in PsA by reducing, but not abolishing, the inflammatory infiltrate,
      adhesion molecule expression, and MMP-3 and proinflammatory cytokine gene
      expression, particularly IL-8, in the synovium. Methotrexate did not reduce
      hypervascularity, which is a prominent differentiating feature of PsA synovium.

PMID- 15476229
TI  - Work above shoulder level and degenerative alterations of the rotator cuff
      tendons: a magnetic resonance imaging study.
AB  - OBJECTIVE: To determine whether work performed with the arms in a highly elevated
      position is associated with alterations in the rotator cuff tendons as assessed
      by magnetic resonance imaging (MRI). METHODS: A cross-sectional study was
      performed in a historical cohort of male machinists, car mechanics, and house
      painters. The participants were right-handed, ages 40-50 years, and had been
      employed in their trades for not less than 10 years. Seventy-one percent of
      invited subjects participated (136 of 192). Lifetime upper arm elevation was
      assessed by direct measurements combined with individual work histories obtained
      by questionnaire and from registry data. Supraspinatus tendinopathy was evidenced
      by MRI signal intensity changes and morphologic alterations. Infraspinatus and
      subscapularis tendinopathy were also assessed. Additional outcomes were
      acromioclavicular joint degeneration and humeral head cysts. The MRI findings
      were evaluated by radiologists who were blinded to exposure status and symptoms.
      RESULTS: An exposure-response relationship was found between lifetime upper arm
      elevation and supraspinatus tendinopathy, with an age-adjusted odds ratio of 1.27
      (95% confidence interval 1.02-1.60) for a 5-month increase in the total number of
      full-time working months spent with the arm elevated >90 degrees . CONCLUSION:
      Work with the arms in a highly elevated position is associated with MRI-diagnosed
      alterations in the supraspinatus tendon. By demonstrating the first part of a
      possible biologic pathway, the study corroborates the work-relatedness of rotator
      cuff disorders.

PMID- 15476230
TI  - New instruments for assessing disability: not quite ready for prime time.

PMID- 15476231
TI  - Intramolecular T cell spreading in unprimed MRL/lpr mice: importance of the U1
      70k protein sequence 131-151.
AB  - OBJECTIVE: To analyze spontaneous T cell spreading against determinants of the U1
      70K protein in young autoimmune MRL/lpr lupus mice, in comparison with the T cell
      spreading occurring in normal BALB/c mice immunized with peptide 131-151 of this
      protein. METHODS: Peripheral blood lymphocytes (PBLs) from both unprimed MRL/lpr
      mice and immunized BALB/c mice were tested for their ability to proliferate ex
      vivo in response to 18 overlapping peptides of the U1-70K spliceosomal protein,
      using assays for lymphocyte proliferation and secretion of interleukin-2.
      RESULTS: The proliferative response to peptides of the U1-70K protein evolved
      rapidly in MRL/lpr mice tested at different ages. At least 5 peptides were
      recognized by PBLs from 8-week-old autoimmune mice, whereas a different peptide
      was recognized by PBLs from MRL/lpr mice at 12 weeks of age. At 15 weeks, the
      proliferative response was weak or negative when assessed with any of the test
      peptides. At least 2 major peptides recognized by MRL/lpr PBLs were also
      recognized by PBLs generated in the BALB/c mice primed with peptide 131-151. We
      further demonstrated that, in preautoimmune MRL/lpr mice, repeated administration
      of phosphorylated peptide 131-151 (called P140), which was shown previously to be
      protective, transiently abolished T cell intramolecular spreading to other
      regions of the 70K protein. CONCLUSION: This is the first study to demonstrate
      that intramolecular T cell spreading effectively occurs in MRL/lpr mice with
      lupus, and that region 131-151 is important in the cascade of events observed in
      the murine lupus response. This sequence might originate a mechanism of tolerance
      spreading that leads to the beneficial effect observed in MRL/lpr mice after
      treatment with the phosphorylated peptide 131-151.

PMID- 15476232
TI  - Breaking the ice: Testing tumor necrosis factor alpha blockade in lupus.

PMID- 15476233
TI  - Therapeutic management of pyoderma gangrenosum.

PMID- 15476234
TI  - Life-threatening hypertriglyceridemia during leflunomide therapy in a patient
      with rheumatoid arthritis.

PMID- 15476235
TI  - Clinical images: Primary systemic amyloidosis masquerading as necrotizing
      vasculitis.

PMID- 15476236
TI  - Enhanced interleukin-1beta and interleukin-18 release in a patient with chronic
      infantile neurologic, cutaneous, articular syndrome.
AB  - Chronic infantile neurologic, cutaneous, articular (CINCA) syndrome is a severe
      inflammatory disease that recently was associated with mutations in CIAS1. It was
      hypothesized that these mutations may lead to enhanced inflammatory responses.
      Herein, we provide evidence that inflammation in the CINCA syndrome is
      characterized by enhanced interleukin-1beta (IL-1beta) and IL-18 release upon
      stimulation of blood cells and show that this release is caspase 1 dependent.

PMID- 15476237
TI  - Should the definition of clinical remission of rheumatoid arthritis be revised?
      Comment on the article by Molenaar et al.

PMID- 15476238
TI  - Direct binding of anti-DNA topoisomerase I autoantibodies to the cell surface of
      fibroblasts in patients with systemic sclerosis.
AB  - OBJECTIVE: Fibroblasts play a crucial role in the development of systemic
      sclerosis (SSc), and antifibroblast antibodies (AFAs) capable of inducing a
      proinflammatory phenotype in fibroblasts have been detected in the sera of SSc
      patients. This study examined the prevalence of AFAs in SSc and other diseases
      and the possible correlation between AFAs and known antinuclear antibody
      specificities in SSc patients. METHODS: Sera from 99 patients with SSc, 123
      patients with other autoimmune and nonautoimmune diseases, and 30 age- and sex
      matched healthy controls were examined. AFA prevalence was assessed by flow
      cytometry and further characterized by indirect immunofluorescence, enzyme-linked
      immunosorbent assay (ELISA), and immunoblotting. Anti-topoisomerase I (anti-topo
      I) from SSc sera were purified by affinity chromatography on topo I. RESULTS:
      AFAs were more common in SSc patients (26.3%) than in any other disease groups
      studied. The presence of AFA was significantly associated with pulmonary
      involvement and death. AFA-positive sera from SSc patients bound to all human and
      rodent fibroblasts tested, but not to human primary endothelial cells or smooth
      muscle cells. All SSc AFAs strongly reacted with topo I by ELISA and
      immunoblotting. The binding intensity of SSc AFAs correlated strongly with
      reactivity against topo I on immunoblots of fibroblast extracts and with the
      immunofluorescence pattern typical of anti-topo I on permeabilized cells. Total
      IgG and affinity-purified anti-topo I from AFA-positive SSc sera were found to
      react with the surface of unpermeabilized fibroblasts by flow cytometry as well
      as by immunofluorescence and confocal microscopy. CONCLUSION: This is the first
      report establishing that AFAs in SSc are strongly correlated with anti-topo I
      and, furthermore, that anti-topo I antibodies themselves display AFA activity by
      reacting with determinants at the fibroblast surface.

PMID- 15476239
TI  - Amelioration of symptoms by enhancement of proprioception in patients with joint
      hypermobility syndrome.
AB  - OBJECTIVE: Joint hypermobility syndrome (JHS) is characterized by an association
      between joint hypermobility and musculoskeletal pains, the latter occurring in
      the absence of any objective indicator of rheumatic disease. The lack of a
      recognizable disease marker makes this condition difficult to identify and
      manage. We previously observed that patients with JHS have impaired
      proprioception compared with that of a matched control group. The purpose of this
      study was to investigate whether a home-based exercise program could produce
      objective enhancement of proprioception as well as alleviate symptoms in JHS.
      METHODS: A threshold detection paradigm was used to assess knee joint
      proprioception, balance was assessed using a balance board, and quadriceps and
      hamstring strength were measured by an isokinetic dynamometer. A visual analog
      scale was used to assess musculoskeletal pain, and quality of life was evaluated
      by a Short Form 36 questionnaire. Assessments were performed before and after an
      8-week program of progressive closed kinetic chain exercises. RESULTS: Following
      the exercise program, proprioceptive acuity increased in 16 of 18 subjects and
      was very significantly improved overall (P < 0.001). There was a comparable
      improvement in performance on the balance board (P < 0.001), and quadriceps and
      hamstring strength also increased significantly. Symptomatic improvement also
      occurred, in terms of both pain (P = 0.003) and quality-of-life (P = 0.029 for
      physical functioning; P = 0.008 for mental health) scores. CONCLUSION:
      Appropriate exercises lead not only to symptomatic improvement, but also to
      demonstrable enhancement of objective parameters such as proprioception.

PMID- 15476240
TI  - Treatment of murine lupus using nucleosomal T cell epitopes identified by bone
      marrow-derived dendritic cells.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by the existence
      of a heterogeneous group of autoantibodies directed against intact nuclear
      structures, such as nucleosomes. The most prominent of these autoantibodies are
      those directed against double-stranded DNA (dsDNA) and histones. The majority are
      of the IgG isotype and show affinity maturation, both of which are known
      hallmarks of T cell help. Much evidence suggests that the nucleosome is a major
      candidate autoantigen in SLE. In this study, a novel strategy was used to
      identify the critical CD4+ T cell autoepitopes in nucleosomes. In addition,
      peptide-based therapy was then performed in a lupus animal model. METHODS: Bone
      marrow (BM)-derived dendritic cells (DCs) were used to examine the self-T cell
      responses against nucleosomes and to characterize the T cell epitope(s) of
      nucleosomes in (NZB x NZW)F1 (BWF1) mice. RESULTS: Several potential auto-T cell
      epitopes of core histone proteins (H2A, H2B, H3, and H4) were identified.
      Nucleosome-pulsed BM-derived DCs elicited release of interleukin-4 and interferon
      gamma, representing a Th0 (i.e., mixed Th1 and Th2) pattern of cytokine
      production. In addition, intradermal immunization of BWF1 mice with the H3(111
      130) peptide not only suppressed the level of anti-dsDNA and anti-single-stranded
      DNA IgG, but also significantly delayed the progress of glomerulonephritis in
      lupus-prone BWF1 mice. CONCLUSION: These results will help in understanding how
      pathogenic autoimmune responses develop in spontaneous SLE. This may potentially
      open the way to T cell-based immunotherapy for lupus.

PMID- 15476241
TI  - Thrombotic thrombocytopenic purpura with severe ADAMTS-13 deficiency in two
      patients with primary antiphospholipid syndrome.
AB  - Arterial thrombotic events, thrombocytopenia, and hemolytic anemia with
      schistocytes may be encountered in the setting of both thrombotic
      thrombocytopenic purpura (TTP) and primary antiphospholipid syndrome (APS). We
      report 2 cases of TTP occurring in patients with definite primary APS. We also
      describe the results of tests for ADAMTS-13 activity in 20 consecutive patients
      with primary APS, as well as tests for antiphospholipid antibodies in 26 patients
      who had TTP, severe ADAMTS-13 deficiency, and ADAMTS-13-inhibiting antibodies. In
      both of the patients with primary APS and TTP, ADAMTS-13 activity was
      undetectable, and ADAMTS-13-inhibiting antibodies were present. None of the 26
      patients with TTP and severe ADAMTS-13 deficiency was positive for the lupus
      anticoagulant. One of these patients had a low level of anticardiolipin
      antibodies (22 IgG phospholipid units). In the 20 patients with primary APS, mean
      ADAMTS-13 activity was 116% (range 44-250%), and no severe deficiency (< 5%) was
      observed. Our findings suggest that primary APS must be added to the list of
      autoimmune disorders that can be complicated by TTP.

PMID- 15476242
TI  - Involvement of inducible costimulator in the exaggerated memory B cell and plasma
      cell generation in systemic lupus erythematosus.
AB  - OBJECTIVE: In systemic lupus erythematosus (SLE), the increased generation of
      memory B cells and plasma cells leads to autoimmune hypergammaglobulinemia and
      destructive immunoglobulin deposits in the kidneys. We undertook this study to
      determine the biologic mechanism driving this overactivation of the B cell
      compartment, which is the central issue in SLE. METHODS: We used flow cytometry
      to analyze expression of the T cell-specific inducible costimulator (ICOS) and
      its ligand (ICOS-L) on B cells obtained from the peripheral blood of SLE
      patients. We correlated ICOS-L expression with the differentiation status of the
      B cells using a large panel of surface antigens. In addition, SLE kidneys were
      analyzed by immunohistology. RESULTS: We found an increased expression of ICOS on
      CD4+ as well as CD8+ T cells in SLE. At the same time, we documented a down
      regulation of ICOS-L on a high proportion of peripheral blood memory B cells.
      Based on in vitro experiments, we inferred that this ICOS-L down-regulation on B
      cells was a signature of recent interaction with ICOS+ T cells in vivo. In the
      kidneys of SLE patients, we found clusters of B cells and plasma cells in close
      contact with ICOS+ T cells. CONCLUSION: Detailed analysis of B cells with down
      regulated ICOS-L suggests that ICOS is one of the forces driving the formation of
      memory B cells and plasma cells in SLE. Furthermore, our identification of plasma
      cells in areas of T cell-B cell interaction in kidneys suggests that components
      of a T cell-driven B cell activation process may take place in peripheral tissues
      in SLE.

PMID- 15476243
TI  - Induction of endothelial cell apoptosis by heat-shock protein 60-reactive
      antibodies from anti-endothelial cell autoantibody-positive systemic lupus
      erythematosus patients.
AB  - OBJECTIVE: To determine whether anti-endothelial cell autoantibodies (AECAs) from
      systemic lupus erythematosus (SLE) patients with the antiphospholipid syndrome
      are involved in the initial endothelial cell (EC) membrane perturbation effect
      that is postulated to provide a target for antiphospholipid antibody (aPL)
      binding and, hence, to trigger the thrombotic cascade. To identify the AECA
      antigenic target on ECs and to determine the mechanism whereby the EC membrane is
      disrupted. METHODS: AECAs from SLE patients were assayed for binding to ECs by
      flow cytometry. Positive AECAs were assayed by immunoblotting, and a consensus
      antigen was identified by mass spectrometry. This candidate antigen was tested in
      recombinant form for AECA recognition. AECAs were affinity-purified on this
      antigen and incubated with ECs to determine their physiologic effects. Anti-Hsp60
      antibody titers were determined by enzyme-linked immunosorbent assay. The
      relationship of anti-Hsp60 status and lupus anticoagulant (LAC) status to
      thrombotic manifestations between disease onset and the last followup visit were
      analyzed. RESULTS: Most of the SLE sera (73%) possessed IgG that bound to the
      surface of ECs. These positive IgG shared reactivity against a 60-kd EC surface
      polypeptide that was identified as human Hsp60. The presence of Hsp60 at the EC
      surface was established using anti-Hsp60 antibodies from commercial sources or
      affinity-purified from SLE sera that bound ECs. Incubation of ECs with these anti
      Hsp60 antibodies induced apoptosis in a time- and dose-dependent manner, as
      determined by Hoechst 33342 dye staining of condensed nuclei and by annexin V
      binding to surface phosphatidylserine. Anti-Hsp60 antibodies were not restricted
      to SLE patients, but were found in patients with other autoimmune diseases.
      However, anti-Hsp60 antibodies were significantly associated with an increased
      frequency of thrombosis when present in combination with LAC in the SLE patients.
      CONCLUSION: The presence of Hsp60 at the surface of ECs serves as a target for
      the anti-Hsp60 antibodies in SLE sera. These anti-Hsp60 antibodies bind to ECs
      and induce apoptosis, particularly phosphatidylserine exposure, thus providing a
      target for the binding of aPL and inducing the subsequent thrombotic cascade.

PMID- 15476245
TI  - Systemic lupus erythematosus genome scan: support for linkage at 1q23, 2q33,
      16q12-13, and 17q21-23 and novel evidence at 3p24, 10q23-24, 13q32, and 18q22-23.
AB  - OBJECTIVE: To identify chromosome regions likely to harbor genes that predispose
      to the development of systemic lupus erythematosus (SLE) by analyzing a full
      genome scan in nuclear families ascertained for siblings with SLE. METHODS:
      Approximately 400 multiallelic markers spaced an average of 10 cM apart were
      genotyped in a multiethnic panel of 238 individuals from 62 multiplex SLE
      families having 88 affected sibling pairs and 456 total sibling pairs. Findings
      were analyzed by 2 model-free statistical linkage procedures. RESULTS: Evidence
      supporting linkage to 4 previously reported (1q23, 2q33, 16q12-13, and 17q21-23)
      and 4 novel (3p24, 10q23-24, 13q32, and 18q22-23) chromosome regions was
      revealed. Stratification by family ethnicity indicated that linkage to 3 regions,
      2q33, 10q23-24, and 18q22-23, was derived primarily from the Caucasian families,
      while linkage to 17q21-23 was seen primarily in the non-Caucasian families.
      CONCLUSION: Linkage to the same chromosome regions in independent cohorts is a
      critical step in finding the genes that predispose to a complex disorder such as
      SLE. Four linked regions also seen in independent SLE cohorts lend credibility to
      the 4 novel regions identified by these analyses. Substantial linkage information
      was gleaned by genotyping and analyzing the unaffected siblings. These results
      provide additional evidence that the SLE clinical phenotype is genetically
      complex, multigenic, and heterogeneous.

PMID- 15476246
TI  - Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXII.
      Predictors of time to the occurrence of initial damage.
AB  - OBJECTIVE: To examine the factors predisposing to initial damage in patients in
      the LUMINA (lupus in minorities: nature versus nurture) cohort, a multiethnic
      cohort of patients with systemic lupus erythematosus (SLE) in the US. METHODS:
      One hundred fifty-eight LUMINA patients with no damage at baseline (time 0)
      according to the Systemic Lupus International Collaborating Clinics Damage Index
      (SDI) and with disease duration > 6 months were followed up for a median of 24
      months (range 5-112 months). Damage was assessed from time 0 to the last visit.
      Predictors of time to initial damage were examined by univariable and
      multivariable Cox proportional hazard regression models. Results were reported as
      hazard ratios (HRs); HR values > or = 1 indicated a shorter time to initial
      damage, and values < 1 indicated a longer time. RESULTS: Initial damage occurred
      in 54 patients (34%), of whom 21 were Hispanics from Texas (39%), 2 were
      Hispanics from Puerto Rico (4%), 21 were African Americans (39%), and 10 were
      Caucasians (19%). The most frequently observed initially involved SDI domains
      (and items) were as follows: renal (primarily proteinuria) in Hispanics from
      Texas and African Americans, integument (primarily scarring alopecia) in
      Hispanics from Puerto Rico, and ocular (primarily cataracts) in Caucasians. By
      multivariable analyses, independent predictors of a shorter time to initial
      damage were Hispanic ethnicity from Texas (HR 2.11, 95% confidence interval [95%
      CI] 1.15-3.88), greater disease activity according to the Systemic Lupus Activity
      Measure (HR 1.09, 95% CI 1.04-1.15), the occurrence of thrombotic events in
      visceral and/or peripheral veins or arteries (HR 7.66, 95% CI 2.13-27.51), and
      prednisone at a dosage of < 10 mg/day (HR 2.53, 95% CI 1.15-5.55). Prednisone at
      a dosage of 10-30 mg/day was found to be protective against the occurrence of
      initial damage (HR 0.46, 95% CI 0.22-0.96). CONCLUSION: Given that damage is a
      predictor of further damage, identifying the factors that may herald the
      occurrence of initial damage has very practical implications for the management
      of patients with SLE. These results need to be considered when evaluating
      therapies for SLE.

PMID- 15476247
TI  - Severity of murine collagen-induced arthritis correlates with increased CYP7B
      activity: enhancement of dehydroepiandrosterone metabolism by interleukin-1beta.
AB  - OBJECTIVE: The endogenous steroid dehydroepiandrosterone (DHEA) has been reported
      to play a role in rheumatoid arthritis (RA). DHEA is metabolized by the P450
      enzyme CYP7B into 7alpha-OH-DHEA, which has immunostimulating properties. This
      study was undertaken to investigate the putative role of CYP7B in arthritis using
      murine collagen-induced arthritis (CIA), an interleukin-1beta (IL-1beta)
      dependent model. METHODS: DBA/1J mice were immunized and administered a booster
      with type II collagen. The presence of 7alpha-OH-DHEA was determined in both
      arthritic and nonarthritic joints and the serum of CIA mice by radioimmunoassay.
      CYP7B messenger RNA (mRNA) expression was analyzed in synovial biopsy samples,
      and in fibroblast-like synoviocytes (FLS) isolated from these synovial biopsy
      samples, by reverse transcriptase-polymerase chain reaction (RT-PCR). In
      addition, the regulatory role of IL-1beta on CYP7B activity in FLS was determined
      using RT-PCR, Western blotting, and high-performance liquid chromatography.
      RESULTS: In knee joint synovial biopsy samples from arthritic mice, 7alpha-OH
      DHEA levels were 5-fold higher than in nonarthritic mice. Elevated levels of
      7alpha-OH-DHEA were accompanied by an increase in CYP7B mRNA expression and were
      positively correlated with disease severity. In serum, no differences in 7alpha
      OH-DHEA levels were observed between arthritic and nonarthritic mice. Incubation
      of FLS with IL-1beta resulted in a dose-dependent increase in 7alpha-OH-DHEA
      formation. In addition, IL-1beta enhanced CYP7B mRNA and CYP7B protein levels in
      FLS. CONCLUSION: Disease progression in CIA is correlated with enhanced CYP7B
      activity, which leads to locally enhanced 7alpha-OH-DHEA levels. Elevated IL
      1beta levels within the arthritic joint may regulate this increase in CYP7B
      activity.

PMID- 15476248
TI  - High prevalence of knee osteoarthritis, pain, and functional limitations in
      female soccer players twelve years after anterior cruciate ligament injury.
AB  - OBJECTIVE: To determine the prevalence of radiographic knee osteoarthritis (OA)
      as well as knee-related symptoms and functional limitations in female soccer
      players 12 years after an anterior cruciate ligament (ACL) injury. METHODS:
      Female soccer players who sustained an ACL injury 12 years earlier were examined
      with standardized weight-bearing knee radiography and 2 self-administered patient
      questionnaires, the Knee Injury and Osteoarthritis Outcome Score questionnaire
      and the Short Form 36-item health survey. Joint space narrowing and osteophytes
      were graded according to the radiographic atlas of the Osteoarthritis Research
      Society International. The cutoff value to define radiographic knee OA
      approximated a Kellgren/Lawrence grade of 2. RESULTS: Of the available cohort of
      103 female soccer players, 84 (82%) answered the questionnaires and 67 (65%)
      consented to undergo knee radiography. The mean age at assessment was 31 years
      (range 26-40 years) and mean body mass index was 23 kg/m2 (range 18-40 kg/m2).
      Fifty-five women (82%) had radiographic changes in their index knee, and 34 (51%)
      fulfilled the criterion for radiographic knee OA. Of the subjects answering the
      questionnaires, 63 (75%) reported having symptoms affecting their knee-related
      quality of life, and 28 (42%) were considered to have symptomatic radiographic
      knee OA. Slightly more than 60% of the players had undergone reconstructive
      surgery of the ACL. Using multivariate analyses, surgical reconstruction was
      found to have no significant influence on knee symptoms. CONCLUSION: A very high
      prevalence of radiographic knee OA, pain, and functional limitations was observed
      in young women who sustained an ACL tear during soccer play 12 years earlier.
      These findings constitute a strong rationale to direct increased efforts toward
      prevention and better treatment of knee injury.

PMID- 15476249
TI  - A human COL2A1 gene with an Arg519Cys mutation causes osteochondrodysplasia in
      transgenic mice.
AB  - OBJECTIVE: An arginine-to-cysteine substitution at position 519 of the COL2A1
      gene causes early generalized osteoarthritis with mild chondrodysplasia in
      humans. In this study, a human COL2A1 gene with the same mutation was introduced
      into a murine genome having 1 or no alleles of the murine Col2a1 gene, and the
      skeletal phenotypes of the transgenic mice were compared with those of control
      mice. METHODS: Mice with 1 allele of the normal murine Col2a1 gene and 1 allele
      of the mutated human COL2A1 gene (n = 10), those with no murine Col2a1 gene and 2
      alleles of the mutated human COL2A1 gene (n = 13), those with no murine Col2a1
      gene and only 1 allele of the mutated COL2A1 gene (n = 9), and normal control
      mice (n = 11) were studied for skeletal abnormalities, using radiographic imaging
      and light microscopic analyses of histologic sections. The collagen network of
      cartilage was also investigated with transmission electron microscopy. RESULTS:
      At 2 months of age, all transgenic mice had dysplastic changes in their long
      bones, flattened vertebral bodies, and osteoarthritic changes in their joints.
      The intervertebral discs of the transgenic animals were degenerated, and their
      histologic structure was disturbed. The changes were more severe in mice with no
      murine Col2a1 allele. CONCLUSION: The human COL2A1 gene with the Arg519Cys
      mutation causes osteochondrodysplasia in mice, as it does in humans.

PMID- 15476250
TI  - Hydraulically loaded trabeculae may serve as springs within the normal femoral
      head.

PMID- 15476251
TI  - Association between spine disc degeneration and type II collagen degradation in
      postmenopausal women: the OFELY study.
AB  - OBJECTIVE: To investigate whether radiologic spine disc degeneration is
      associated with increased type II collagen (CII) degradation products in the
      urine of postmenopausal women, independently of radiologic knee osteoarthritis
      (OA) and clinical hand OA. METHODS: The study group comprised 324 postmenopausal
      women ages 58-94 years who had no treatment or disease that could alter bone
      metabolism. Lateral radiographs of the thoracic and lumbar spine were obtained in
      each woman and scored for disc space narrowing (DSN) and osteophytes. Fixed
      flexion posteroanterior radiographs of the knee were obtained to assess
      femorotibial knee OA. In all women, hand OA was assessed by clinical examination,
      and the level of urinary C-terminal crosslinking telopeptide of CII (CTX-II), a
      biologic marker of CII degradation, was measured. RESULTS: The prevalences of
      radiographic lumbar and thoracic spine disc degeneration, knee OA, and clinical
      hand OA were 84%, 88%, 35%, and 58%, respectively. After adjustment for age and
      body mass index (BMI), patients with lumbar spine DSN grade > or = 1 had, on
      average, 34% higher CTX-II levels compared with the other women (P = 0.0005),
      whereas no association was observed with lumbar spine osteophytes. No significant
      association between thoracic spine DSN or osteophytes and urinary CTX-II levels
      was observed. Multivariate analysis of variance showed that, after adjustment for
      age and BMI, lumbar spine DSN (P = 0.0049), knee OA (P = 0.0055), and clinical
      hand OA (P = 0.0060) were, independently of each other, associated with CTX-II
      levels. Thus, patients with lumbar spine DSN, knee OA, and clinical hand OA had
      CTX-II levels 80% higher (P < 0.0001 after adjustment for age and BMI) than those
      of patients with no lumbar spine DSN, no radiologic knee OA, and no clinical hand
      OA. CONCLUSION: Postmenopausal women with lumbar spine disc degeneration are
      characterized by increased CII degradation. The contribution of lumbar spine DSN
      to CII degradation was similar to, and independent of, the contribution of
      radiologic knee OA or clinical hand OA. Lumbar spine disc degeneration in elderly
      patients should be assessed when analyzing levels of CTX-II in studies of knee,
      hip, and hand OA.

PMID- 15476252
TI  - Quantification of cortical bone loss and repair for therapeutic evaluation in
      collagen-induced arthritis, by micro-computed tomography and automated image
      analysis.
AB  - OBJECTIVE: Ex vivo and in vivo micro-computed tomography (micro-CT) combined with
      a novel image analysis algorithm were used to quantify cortical bone loss and
      periosteal new bone formation for therapeutic evaluation in a murine model of
      collagen-induced arthritis. METHODS: An automated algorithm was created to locate
      5 metatarsophalangeal and 3 metacarpophalangeal joints in 3-dimensional micro-CT
      images of mouse paws for evaluation of joint cortical bone volume (JCBV) within
      close proximity of the joints as well as cortical bone mineral density and
      periosteal new bone formation within the paws. For validation, automated
      estimates of JCBV were compared with radiographic visual scores (RVS) in 4
      treatment groups (n = 9 per group): rat anti-mouse CD11a monoclonal antibody,
      methotrexate (MTX), anti-CD11a plus MTX, and saline only. In a separate study,
      serial images of hind limbs were evaluated in 2 treatment groups: murine tumor
      necrosis factor receptor II-Fc fusion protein (mTNFRII; n = 10) and control
      antibody (n = 7). RESULTS: Automated estimates of the JCBV were significantly
      correlated with the RVS (hind paws R = -0.94, front paws R = -0.81, combined R = 
      0.87). The anti-CD11a group had significantly higher JCBV compared with controls.
      In the serial study, the automated estimate of JCBV detected significant
      treatment effects in the mTNFRII-Fc group compared with controls. Cortical bone
      mineral density was significantly higher in all treatment groups compared with
      controls. CONCLUSION: Micro-CT combined with a novel image analysis technique
      (estimation of JCBV) provides a fully automated means to quantify bone
      destruction in a mouse model of rheumatoid arthritis.

PMID- 15476254
TI  - The "enthesis organ" concept: why enthesopathies may not present as focal
      insertional disorders.
AB  - OBJECTIVE: The Achilles tendon insertion is associated with a complex of adjacent
      fibrocartilages, a bursa, and a fat-pad, and is functionally much more than a
      focal insertion. This has important implications for a better understanding of
      the spondylarthropathies (SpA). However, the degree to which other insertions
      form comparable "enthesis organs" has not been established. The aim of this study
      was to demonstrate the applicability of the enthesis organ concept to other
      insertion sites. METHODS: Both joint-related (articular) and extraarticular
      entheses were removed from 28 sites in the limbs of formalin-fixed cadavers (age
      at death 70-101 years) that had been donated for anatomic study. The samples were
      prepared for paraffin histologic analysis and sectioned longitudinally. The
      presence and extent of enthesis organs was evaluated at each site in serial
      sections stained with Masson's trichrome and toluidine blue. RESULTS: Articular
      enthesis organs were found at 14 entheses, including the attachments of the
      digital extensor tendons and collateral ligaments, the cruciate ligaments,
      tibialis anterior, the lateral collateral ligament of the knee, and the popliteal
      tendon. Extraarticular enthesis organs were seen at 2 sites, the biceps brachii
      and patellar tendon insertions. In all enthesis organs, sesamoid and/or
      periosteal fibrocartilage was present in close association with synovium.
      CONCLUSION: The concept of an enthesis organ is of general significance in
      understanding attachment sites and may explain the diverse pathologic changes,
      including synovitis, bursitis, and extracapsular changes, seen adjacent to
      tendon/ligament entheses in SpA. These findings may provide insight into the
      reason the target tissues in SpA are apparently so diverse.

PMID- 15476255
TI  - Antigen-specific immunomodulation of collagen-induced arthritis with tumor
      necrosis factor-stimulated dendritic cells.
AB  - OBJECTIVE: Dendritic cells (DCs) are crucial for the initiation of T cell
      immunity and therefore play an important role in the initiation and regulation of
      immune responses in arthritis. Full mobilization of effector T cells depends on
      the proper maturation of DCs. Current evidence indicates that the type of T cell
      response induced is crucially dependent on the activation status of the DCs. In
      this study, we explored the immunologic effects of differentially matured DCs on
      the development of collagen-induced arthritis (CIA). METHODS: Bone marrow-derived
      DCs were cultured in the presence of granulocyte-macrophage colony-stimulating
      factor (GM-CSF). Before immunization with bovine type II collagen (CII) protein,
      mice were repeatedly injected with DCs that had been pulsed with CII. Immature,
      semimature, or fully mature DCs were injected. Mice were boosted on day 21 after
      CII immunization, and the disease course was monitored. RESULTS: While
      vaccination with immature or lipopolysaccharide-activated DCs had no significant
      effect on the disease course, administration of antigen-loaded, tumor necrosis
      factor (TNF)-modulated DCs propagated in GM-CSF with or without interleukin-4
      resulted in a delayed onset of arthritis and a lower clinical score. The response
      was antigen-specific, since TNF-treated DCs pulsed with a control antigen did not
      modify the disease course. A specific decrease in the collagen-specific "Th1
      associated" IgG2a response was observed, whereas IgG1 titers were unaffected.
      CONCLUSION: CIA can be prevented through vaccination with TNF-matured DCs in an
      antigen-specific manner. These findings provide a rationale for immunotherapy
      using DCs in rheumatoid arthritis.

PMID- 15476256
TI  - Analysis of immobilized L-cysteine on polymers.
AB  - Recently, we reported that L-cysteine attached to polymeric biomaterials, without
      prior nitrosation, enhances the hemocompatibility of biomaterials via exploiting
      endogenous nitric oxide (NO). As part of the polymer optimization process to
      further enhance platelet inhibition, a kinetic model is being developed to
      predict the release rate of NO. A key model parameter is the immobilized
      concentration of L-cysteine. This article demonstrates how several
      chemiluminescence-based assays, previously utilized for measuring thiols in
      solution, were successfully adapted to quantify immobilized L-cysteine. The
      assays showed that the immobilized L-cysteine on the modified PET sample is
      within the range of 4.1 to 6.5 nmol/cm(2). An advantage of using the more
      successful chemiluminescence-based assay is that it can accurately measure molar
      concentrations of any thiol-containing compound with a detection limit in the
      pmol range. The major disadvantage is that L-cysteine must first be broken off of
      the polymer and released into solution prior to measurement, therefore leaving
      the sample unable to be reused. Other thiol-measuring techniques, such as
      fluorescence microscopy and X-ray photoelectron spectroscopy (XPS), were used to
      provide qualitative and semiquantitative analysis to substantiate the polymer
      development.

PMID- 15476257
TI  - Measurements of protein sequence-structure correlations.
AB  - Correlations between protein structures and amino acid sequences are widely used
      for protein structure prediction. For example, secondary structure predictors
      generally use correlations between a secondary structure sequence and
      corresponding primary structure sequence, whereas threading algorithms and
      similar tertiary structure predictors typically incorporate interresidue contact
      potentials. To investigate the relative importance of these sequence-structure
      interactions, we measured the mutual information among the primary structure,
      secondary structure and side-chain surface exposure, both for adjacent residues
      along the amino acid sequence and for tertiary structure contacts between
      residues distantly separated along the backbone. We found that local interactions
      along the amino acid chain are far more important than non-local contacts and
      that correlations between proximate amino acids are essentially uninformative.
      This suggests that knowledge-based contact potentials may be less important for
      structure predication than is generally believed.

PMID- 15476258
TI  - Myoelectric manifestations of fatigue during exposure to hypobaric hypoxia for 12
      days.
AB  - Lack of oxygen, as occurs at high altitude (HA), leads to a number of adaptive
      processes in muscle, but their precise nature is unclear. To better understand
      mechanisms of adaptations of the neuromuscular system to HA, we collected surface
      electromyographic (EMG) signals during a 12-day stay at 5,050 m above sea level
      (SL). The aim was to investigate the effect of hypobaric hypoxia on muscle-fiber
      membrane and motor-unit control properties. Surface EMG signals were recorded
      from the dominant biceps brachii muscle of six subjects at HA and 3 months after
      their return to SL. Supramaximal electrical stimuli (25 HZ) were delivered and
      voluntary isometric contractions at 40 and 80% of maximal voluntary torque were
      performed in 10 experimental sessions at HA and in 3 at SL. Maximal isometric
      torque was not altered at HA. Surface EMG spectral frequencies at the beginning
      of the voluntary contractions were greater at HA than SL. The rates of change of
      spectral frequencies and conduction velocity during the voluntary contractions
      were significantly larger at HA than SL. No differences in EMG variables were
      observed in the electrically elicited contractions. The maximal torque and
      surface EMG variables did not depend on the day of measure at HA. It was
      concluded that acute exposure to hypobaric hypoxia does not significantly affect
      the muscle-fiber membrane properties but does impact motor-unit control
      properties. This provides new insights in the understanding of motor control in
      extreme conditions of oxygen reduction, with relevance for sport and
      rehabilitation medicine, and may also explain the pathophysiological adaptations
      of the neuromuscular system occurring in such disorders as chronic obstructive
      pulmonary disease.

PMID- 15476259
TI  - Scoring function for automated assessment of protein structure template quality.
AB  - We have developed a new scoring function, the template modeling score (TM-score),
      to assess the quality of protein structure templates and predicted full-length
      models by extending the approaches used in Global Distance Test (GDT)1 and
      MaxSub.2 First, a protein size-dependent scale is exploited to eliminate the
      inherent protein size dependence of the previous scores and appropriately account
      for random protein structure pairs. Second, rather than setting specific distance
      cutoffs and calculating only the fractions with errors below the cutoff, all
      residue pairs in alignment/modeling are evaluated in the proposed score. For
      comparison of various scoring functions, we have constructed a large-scale
      benchmark set of structure templates for 1489 small to medium size proteins using
      the threading program PROSPECTOR_3 and built the full-length models using
      MODELLER and TASSER. The TM-score of the initial threading alignments, compared
      to the GDT and MaxSub scoring functions, shows a much stronger correlation to the
      quality of the final full-length models. The TM-score is further exploited as an
      assessment of all 'new fold' targets in the recent CASP5 experiment and shows a
      close coincidence with the results of human-expert visual assessment. These data
      suggest that the TM-score is a useful complement to the fully automated
      assessment of protein structure predictions. The executable program of TM-score
      is freely downloadable at http://bioinformatics.buffalo.edu/TM-score.

PMID- 15476260
TI  - Sphingosine-1-phosphate plays a role in the suppression of lateral pseudopod
      formation during Dictyostelium discoideum cell migration and chemotaxis.
AB  - Sphingosine-1-phosphate (S-1-P) is a bioactive lipid that plays a role in diverse
      biological processes. It functions both as an extracellular ligand through a
      family of high-affinity G-protein-coupled receptors, and intracellularly as a
      second messenger. A growing body of evidence has implicated S-1-P in controlling
      cell movement and chemotaxis in cultured mammalian cells. Mutant D. discoideum
      cells, in which the gene encoding the S-1-P lyase had been specifically disrupted
      by homologous recombination, previously were shown to be defective in pseudopod
      formation, suggesting that a resulting defect might exist in motility and/or
      chemotaxis. To test this prediction, we analyzed the behavior of mutant cells in
      buffer, and in both spatial and temporal gradients of the chemoattractant cAMP,
      using computer-assisted 2-D and 3-D motion analysis systems. Under all
      conditions, S-1-P lyase null mutants were unable to suppress lateral pseudopod
      formation like wild-type control cells. This resulted in a reduction in velocity
      in buffer and spatial gradients of cAMP. Mutant cells exhibited positive
      chemotaxis in spatial gradients of cAMP, but did so with lowered efficiency,
      again because of their inability to suppress lateral pseudopod formation. Mutant
      cells responded normally to simulated temporal waves of cAMP but mimicked the
      temporal dynamics of natural chemotactic waves. The effect must be intracellular
      since no homologs of the S-1-P receptors have been identified in the
      Dictyostelium genome. The defects in the S-1-P lyase null mutants were similar to
      those seen in mutants lacking the genes for myosin IA, myosin IB, and clathrin,
      indicating that S-1-P signaling may play a role in modulating the activity or
      organization of these cytoskeletal elements in the regulation of lateral
      pseudopod formation.

PMID- 15476261
TI  - Tonic modulation of inhibition by dopamine D4 receptors in the rat hippocampus.
AB  - Dopaminergic pathways have been recognized to play a critical role in cognition
      and emotion. Dopamine D2 and D4 receptors are the target for most common
      antipsychotics and their activation, particularly those in the medial temporal
      lobe structures, has been associated with their beneficial actions. The
      entorhinal cortex, which is the cortical area most consistently and severely
      affected in schizophrenia constitutes the main input to the hippocampus. Since
      the D4 receptor is highly concentrated in the hippocampus, and the effects of the
      selective activation of D4 receptors on the input/output function of the
      hippocampal formation are poorly understood, we sought to investigate the role of
      these receptors in the synaptic transmission and paired-pulse inhibition from the
      perforant path to area CA1 and the dentate gyrus. The D4 receptor antagonist,
      clozapine, translated paired-pulse inhibition into paired-pulse potentiation in
      both perforant path targets. By contrast, the D2/D3 antagonist quinpirole had no
      effect. The blockade of the D2/3 receptors with sulpiride, and of D1/5 receptors
      with SCH-23390, has no effect on paired-pulse inhibition, suggesting that these
      receptors are not involved in feedforward inhibition in these hippocampal areas.
      Interestingly, the perfusion of the D4 selective antagonist, L-745,870 (Patel et
      al., 1997: J Pharmacol Exp Ther 283:636-647) during the blockade of D2/3 and D1/5
      receptors produces a reversible decrease in paired-pulse inhibition in CA1, but
      not in the DG. Our results show that endogenous DA tonically modulates
      feedforward inhibition in area CA1 and the dentate gyrus through the activation
      of D4 receptors located in the interneuronal population of these hippocampal
      regions. Since activation of the D4 receptor inhibits GABA release and GABAergic
      synaptic transmission, we suggest that the perforant path stimulates interneurons
      that have the D4 receptor and that, in turn, contact other interneurons that
      synapse onto pyramidal cells. (c) 2004 Wiley-Liss, Inc.

PMID- 15476262
TI  - Surface chemistry mediates adhesive structure, cytoskeletal organization, and
      fusion of macrophages.
AB  - Surface chemistry modulates many critical functions of monocyte/macrophages such
      as adhesion, fusion, spreading, phagocytosis, and secretion. In this study, we
      investigated the effect of silicone modification on adhesive structure
      development and cytoskeletal reorganization of adherent macrophages on
      polyurethanes. Confocal scanning laser microscopy (CSLM) was used for qualitative
      and quantitative evaluation of cytoskeletal reorganization of adherent
      macrophages. Data presented here showed less spreading for adherent cells on
      silicone-modified materials due to the higher hydrophobicity and protein
      adsorption profile. This decrease in spreading was accompanied by less F-actin
      content in adherent cells on silicone-modified polyurethanes and PDMS control,
      indicating that silicone modification reduces the strength of adhesion. With the
      addition of interleukin-4 (IL-4) at days 3 and 7 to our culture, adherent cell
      morphology dramatically changed. The change in morphology led to higher
      macrophage fusion and foreign body giant cell (FBGC) formation on silicone
      modified materials after 10 days. In addition, mannose receptor (MR) expression
      was up-regulated on the silicone-modified polyurethanes and PDMS control in the
      presence of IL-4. Up-regulation of MR expression suggests an alternatively
      activated phenotype for adherent macrophages, which is accompanied with an
      attenuated proinflammatory cytokine production and reactive oxygen secretion. It
      appears that silicone modification accelerates acquisition of an alternative
      macrophage and FBGC phenotype, which may then result in increased polyurethane
      biostability.

PMID- 15476263
TI  - Dynamics of endocytic traffic of Entamoeba histolytica revealed by confocal
      microscopy and flow cytometry.
AB  - Entamoeba histolytica, the protozoan parasite of humans, manifests constitutive
      endocytosis to obtain nutrients and, when induced to express invasive behavior,
      as a means of ingesting and processing host cells and tissue debris. E.
      histolytica trophozoites were grown in liquid axenic medium that contained
      fluorescently labeled fluid-phase markers, so that the kinetics of uptake, the
      transit of loaded endosomes through the cytoplasm, and the time of release of the
      markers could be monitored by flow cytometry. Confocal microscopy of live
      trophozoites revealed uptake of fluid by avid macropinocytosis and the occurrence
      of fusion between young and older endosomes, as well as between pinosomes and
      phagosomes containing bacteria. Endosomes were rapidly acidified, then gradually
      neutralized; finally, indigestible material was released. Transit of endosomes
      containing fluid-phase markers required about 2 h. Uptake and release of fluid
      phase markers were impaired by drugs that inhibited actin dynamics and actin
      myosin interaction; uptake was also impaired by inhibition of PI 3-kinase. A
      striking feature of the trophozoites was the great heterogeneity of their
      endocytic behavior.

PMID- 15476264
TI  - The candidate oncogene ZNF217 is frequently amplified in colon cancer.
AB  - In this study we have defined the changes in gene copy number of the candidate
      oncogene ZNF217 during colon cancer development and progression. This gene is
      mapped to chromosome 20q and lies within 20q13.2, a region which we have
      previously shown to be highly amplified in colorectal cancer by comparative
      genomic hybridization. The gene copy number of ZNF217 was assessed in 100 colon
      carcinomas (19 Dukes' A, 42 Dukes' B and 39 Dukes' C), 13 colonic adenomas and 10
      normal colon samples. DNA extracted from laser microdissected cells was amplified
      by multiplex real-time PCR at two distinct gene loci--ZNF217 and beta-globin
      (control gene)--on an ABI7700 sequence detection system. Of the 100 colon cancers
      studied, 61 showed some level of amplification of ZNF217, 15 had loss of ZNF217,
      while 24 were diploid. All the adenomas except one were diploid. In this study we
      have found that ZNF217 amplification is a frequent event in colon cancer and that
      the extent of its amplification varies markedly between tumours (range 3-13
      copies). There was a trend toward poorer survival in patients whose cancers had
      either gain or loss of ZNF217.

PMID- 15476266
TI  - Opposite effect of oxidative stress on inducible nitric oxide synthase and haem
      oxygenase-1 expression in intestinal inflammation: anti-inflammatory effect of
      carbon monoxide.
AB  - Inducible nitric oxide synthase (iNOS) is expressed in intestinal epithelial
      cells (IEC) of patients with active inflammatory bowel disease (IBD) and in IEC
      of endotoxaemic rats. The induction of iNOS in IEC is an element of the NF-kappaB
      mediated survival pathway. Haem oxygenase-1 (HO-1) is an AP-1-regulated gene that
      is induced by oxidative stress. The enzyme produces carbon monoxide (CO), which
      may attenuate the inflammatory response. The aim of this study was to investigate
      the regulation and interaction of iNOS and HO-1 in response to inflammation and
      oxidative stress. Male Wistar rats were treated with the thiol-modifying agent
      diethylmaleate (DEM) to induce oxidative stress and rendered endotoxaemic by LPS
      injection. Human colonic biopsies and the human colon carcinoma cell line DLD-1
      were treated with DEM and the lipid peroxidation end-product 4-hydroxynonenal to
      induce oxidative stress and exposed to cytokine mix (CM) to mimic inflammation.
      In some experiments, cells were incubated with 250-400 ppm CO prior to and during
      stimulation with CM. HO-1 and iNOS expression was evaluated by RT-PCR, western
      blotting, and immunohistology. NF-kappaB activation was evaluated by EMSA. LPS
      induced iNOS but not HO-1 in epithelial cells of the ileum and colon. Oxidative
      stress strongly induced HO-1 in epithelial and inflammatory cells. Combined
      oxidative stress and endotoxaemia decreased iNOS expression but strongly induced
      HO-1 expression. Similarly, CM induced iNOS but not HO-1 in colonic biopsies and
      DLD-1 cells. Oxidative stress prevented iNOS induction in an NF-kappaB-dependent
      manner but increased HO-1 expression in CM-exposed DLD-1 cells. CO inhibited iNOS
      mRNA induction in CM-stimulated DLD-1 cells. These data demonstrate opposite
      regulation of iNOS and HO-1 in intestinal epithelial cells in response to
      cytokine exposure and oxidative stress. These findings suggest that iNOS (NF
      kappaB driven) and HO-1 (AP-1 driven) represent mutually exclusive survival
      mechanisms in intestinal epithelial cells.

PMID- 15476267
TI  - Early recruitment of phagocytes contributes to the vascular inflammation of giant
      cell arteritis.
AB  - Vascular inflammation in giant cell arteritis is generally described as a process
      involving dendritic cells, T-lymphocytes, and effector tissue macrophages. Less
      is known about the contribution of phagocytes that are recruited early, such as
      monocytes and neutrophils. These cells express and secrete pro-inflammatory S100
      proteins which directly activate endothelial cells. In this study the expression
      of S100A8/S100A9 and S100A12, pro-inflammatory proteins specific for early
      recruited phagocytes, was studied in biopsies from 36 patients with giant cell
      arteritis. In addition, serum concentrations of these proteins were analysed in
      serum samples from 42 patients and 35 healthy controls. The S100A8/S100A9 complex
      was found to be abundant in the adventitia and media in affected arteries.
      Besides neutrophils, cells expressing these proteins belonged to a pro
      inflammatory subtype of CD68-positive monocytes. In contrast, S100A12 expression
      was restricted to neutrophils that were found around the vasa vasorum within the
      adventitial layer. Both S100A8/S100A9 and S100A12 serum concentrations were
      significantly higher in patients with giant cell arteritis than in healthy
      controls. In conclusion, recently recruited phagocytes expressing pro
      inflammatory S100 proteins take part in the vascular inflammation of giant cell
      arteritis. They may play important roles at the vasa vasorum of affected vessels,
      which represent sites of entry for recruited inflammatory cells. These data
      indicate that phagocytes within the adventitia and media contribute to the
      process of inflammation via release of the pro-inflammatory S100 proteins S100A8,
      S100A9, and S100A12.

PMID- 15476265
TI  - BDNF protects against stress-induced impairments in spatial learning and memory
      and LTP.
AB  - The present study investigated whether infusion of brain-derived neurotrophic
      factor (BDNF) could ameliorate stress-induced impairments in spatial learning and
      memory as well as hippocampal long-term potentiation (LTP) of rats. Chronic
      immobilization stress (2 h/day x 7 days) significantly impaired spatial
      performance in the Morris water maze, elevated plasma corticosterone, and
      attenuated LTP in hippocampal slices from these animals as compared with normal
      control subjects. BDNF was infused into the left hippocampus (0.5 mul/h) for 14
      days, beginning 7 days before the stress exposure. The BDNF group was protected
      from the deleterious effects of stress and performed at a level indistinguishable
      from normal control animals despite the presence of elevated corticosterone. BDNF
      alone and sham infusions had no effect on performance or LTP. These results
      demonstrate that spatial learning and memory, and LTP, a candidate neural
      substrate of learning and memory, are compromised during chronic stress, and may
      be protected by BDNF administration.

PMID- 15476268
TI  - Frequent overexpression of multiple ErbB receptors by head and neck squamous cell
      carcinoma contrasts with rare antibody immunity in patients.
AB  - In an effort to elucidate the role of ErbB receptors in human head and neck
      squamous cell carcinoma (HNSCC), expression abnormalities and subcellular
      localization of epidermal growth factor receptor (EGFR), ErbB2, ErbB3, and ErbB4
      were investigated along with EGF and tenascin by immunohistochemistry in 38
      carcinomas as compared to adjacent normal mucosa of 24 cases. Although tumour
      specific overexpression affected each ErbB receptor (EGFR 47%, ErbB2 29%, ErbB3
      21%, ErbB4 26%), EGFR abnormalities were most prevalent. The latter, and
      overexpression of more than two ErbB receptors in the same tumour, which always
      included EGFR, correlated with metastatic disease. ErbB products were
      specifically detected on the cell membrane and in the cytoplasm. In contrast,
      ErbB4 was uniquely localized to the nucleus in 7 carcinomas and a tumour-derived
      cell line, indicating a role for regulated intramembrane proteolysis resulting in
      nuclear ErbB4 translocation in HNSCC. Expression of prototype ligand EGF or low
      affinity stromal activator tenascin correlated significantly with EGFR
      overexpression, implying chronic EGFR activation. Simultaneous overexpression of
      additional ErbB receptors in most of these cases suggested recurrent involvement
      of receptor heterodimers. In spite of frequent ErbB receptor alterations,
      autologous ErbB serum antibodies were rare, with only 1 of 38 tumour patients
      exhibiting an ErbB2-specific immune response. Based on upregulation of several
      known immunosuppressive molecules, scarcity of ErbB-specific antibodies is
      consistent with attenuation of natural tumour-specific immune responses in HNSCC.

PMID- 15476269
TI  - Molecular cytogenetic analysis of human spermatocytic seminomas.
AB  - We performed comparative genomic hybridization (CGH) on 8 formalin-fixed,
      paraffin wax-embedded primary spermatocytic seminomas (SS) from 7 patients, one
      of whom developed metastatic disease. In general, this tumour type is not
      associated with development of metastases. Since there are only few reported
      cases of metastatic SS in the literature, this study is the first report of
      chromosomal constitution in a patient with metastatic disease. Chromosomal
      imbalances were observed in all 8 tumours analysed by CGH. Frequent copy number
      alterations were enh(9), dim(16 or 16p), enh(20) and enh(X), each in 6 samples,
      followed by dim(7) in 4, and enh(1), enh(18) and dim(15), each in 3 samples. In
      addition to the CGH analysis, interphase fluorescence in situ hybridisation (I
      FISH) was applied to evaluate the CGH results and to define the size of the
      aberrant cell population. Interphase cytogenetics showed gain of material on
      chromosomes 9 and X in all tumours analysed. Overall, the I-FISH results were in
      agreement with the CGH data. In conclusion, gain of chromosome 9 seems to be
      restricted to SS and point to an important role for this aberration in the
      development of this tumour type.

PMID- 15476270
TI  - The tumour suppressor gene CEACAM1 is completely but reversibly downregulated in
      renal cell carcinoma.
AB  - CEACAM1 acts as a tumour suppressor in various epithelial tumours. On the other
      hand, de novo expression of CEACAM1 is strongly associated with reduced disease
      free survival of melanoma and non-small cell lung carcinoma patients. Since
      effector functions of natural killer and T cells are inhibited by homophilic
      CEACAM1 interaction, immune escape could be responsible for the poor prognosis of
      these patients. Here, we describe CEACAM1 expression in normal kidney, renal
      adenomas and renal cell carcinomas (RCC) using a novel antibody generated by
      genetic immunization. In normal kidney, CEACAM1 was found in epithelial cells of
      proximal tubules and in endothelial cells. In contrast, tumour cells of 30 clear
      cell, three chromophobic, and two chromophilic RCCs were completely devoid of
      CEACAM1. Renal adenomas also lacked CEACAM1 expression. Similarly, RCC cell lines
      CaKi1, CaKi2, A498, and RCC26 exhibited no or low-level CEACAM1 expression.
      However, CEACAM1 expression was transiently induced in A498 cells upon contact
      with allogeneic CD8+ T cells, mediated at least in part by interferon-gamma.
      Furthermore, the majority of tumour-infiltrating T and NK cells expressed CEACAM1
      upon stimulation. Thus, transient expression of the tumour suppressor CEACAM1 by
      tumour cells and subsequent homophilic interaction with CEACAM1 on tumour
      infiltrating lymphocytes could represent a novel immune escape mechanism in RCC.

PMID- 15476271
TI  - Significance of beta-catenin and pRB pathway components in malignant ovarian germ
      cell tumours: INK4A promoter CpG island methylation is associated with cell
      proliferation.
AB  - To clarify the mechanisms underlying cell cycle promotion in malignant germ cell
      tumours of the ovary (MGCTOs), beta-catenin and components of the pRB pathway,
      cyclin D1 and p16, were analysed in relation to cell proliferation.
      Immunohistochemically, p16 protein was not expressed in a number of MGCTOs (9 of
      42 tumours: 21.4%) and was associated with p16 gene (INK4A) promoter 5'-CpG
      islands methylation. Amplification of the cyclin D1 gene (CCND1) was detected in
      a small number of MGCTOs (5 of 42 tumours: 13.5%). Reduced expression of p16 due
      to promoter methylation correlated significantly with increased cell
      proliferation as evidenced by Ki-67 labelling index (p < 0.001) and mitotic index
      (p < 0.01). In some tumour types, nuclear localization of beta-catenin has been
      reported to be associated with beta-catenin gene (CTNNB1) mutation, cyclin D1
      overexpression, and increased cell proliferation. Nuclear localization of beta
      catenin, which was observed in MGCTOs other than dysgerminoma, was not associated
      with cyclin D1 expression and increased cell proliferation, but appeared to be
      related to tumour differentiation. Furthermore, CTNNB1 mutations were not
      detected in any of the MGCTOs examined. Our results suggest that reduced
      expression of p16 due to INK4A promoter methylation is one of the principal
      factors that promote cell proliferation in MGCTOs. Thus, p16 may be a novel
      target for gene therapies to treat MGCTOs.

PMID- 15476272
TI  - Treatment of breast carcinoma in patients with clinically negative axillary lymph
      nodes using radiotherapy versus axillary dissection.
AB  - BACKGROUND: The role of axillary lymph node dissection (AxD) for patients with
      breast carcinoma who have clinically negative lymph nodes (cN0) and undergo
      breast-conserving therapy has been controversial. If patients do not undergo AxD,
      then it is uncertain whether specific lymph node irradiation should be given. The
      authors compared the results obtained from patients w ho underwent AxD with the
      results from patients who received axillary irradiation (AxR) using one of two
      radiotherapy techniques. METHODS: Patients with T1-T2cN0 breast carcinoma were
      treated from 1983 to 2002 with either AxD (80 patients) or AxR (1134 patients
      received tangential-field [2-field] irradiation, and 303 patients received 3
      field irradiation). The median follow-up was 161 months for the AxD group and 66
      months for the AxR group (55 months for patients who received tangential-field
      irradiation, and 122 months for patients who received 3-field irradiation).
      RESULTS: One patient in the AxD group and 35 patients in the AxR group had
      axillary recurrences. The 10-year cumulative axillary recurrence rates were 1.3%
      and 4.6% for the AxD group and the AxR group, respectively (P = 0.21). For
      patients with T1 tumors, the 10-year overall survival rates for the two groups
      were 94.7% and 92.7%, respectively (P = 0.34); and, for patients with T2 tumors,
      the 10-year overall survival rates were 92.5% and 89.1%, respectively (P = 0.34).
      In the AxR group, the 5-year axillary recurrence rates were 2.5% for patients who
      received tangential-field irradiation and 1.7% for patients who received 3-field
      irradiation (P = 0.18), and the 5-year regional recurrence rates for the two
      groups were 4.8% and 2.4%, respectively (P = 0.048). On multivariate analysis,
      positive lymphovascular invasion, outer tumor location, and larger tumor size
      were significant risk factors for regional failure. CONCLUSIONS: For patients
      with cN0 breast carcinoma, AxD and AxR yielded the same overall survival rates.
      Most patients can be treated safely with tangential-field irradiation alone.
      Patients who are at increased risk of regional failure may benefit from three
      field irradiation.

PMID- 15476273
TI  - Anagrelide for thrombocytosis in myeloproliferative disorders: a prospective
      study to assess efficacy and adverse event profile.
AB  - BACKGROUND: Although the platelet count does not correlate with the rate of
      thrombosis, there is evidence that a strict control of the platelet count
      decreases the incidence of thromboembolic complications in essential
      thrombocythemia. In the current study, the authors evaluated the efficacy and
      tolerability of anagrelide in thrombocytosis associated with myeloproliferative
      disorders. METHODS: The study cohort comprised 97 patients (n = 69 females, n =
      28 males) with a median age of 59 years (range, 21-80 years). Patients with
      essential thrombocythemia (n = 79) or with thrombocytosis due to polycythemia
      vera (n = 16) or to chronic idiopathic myelofibrosis (n = 2) were enrolled in the
      multicenter, prospective study. Patients received anagrelide at a starting dose
      of 0.5 mg twice per day, which was then adjusted for each patient. RESULTS:
      Treatment with anagrelide resulted in a rapid decrease in the platelet count,
      from a median baseline platelet count of 743 x 10(9)/L to a median platelet count
      of 441 x 10(9)/L after 6 months (P < 0.0001). The proportion of patients with a
      platelet count < 600 x 10(9)/L increased from 30% at baseline to 77% after the 6
      month study period. The rate of major thrombotic complications significantly
      decreased from 5% to 2% (P = 0.2568). For patients with essential
      thrombocythemia, the reduction of major thromboembolic complications was
      significant (P = 0.0455). The rate of minor thromboembolic complications
      decreased from 25% before anagrelide treatment to 14% during anagrelide treatment
      (P = 0.0278). No severe side effects were observed during the study period. There
      was, however, evidence that concomitant administration of acetylsalicylic acid
      may increase bleeding tendency. CONCLUSIONS: Anagrelide was an effective and well
      tolerated treatment modality for reducing platelet counts in both newly diagnosed
      and pretreated patients with thrombocytosis due to myeloproliferative disorders.

PMID- 15476274
TI  - A highly sensitive and quantitative telomerase activity assay with pancreatic
      juice is useful for diagnosis of pancreatic carcinoma without problems due to
      polymerase chain reaction inhibitors: analysis of 100 samples of pancreatic juice
      from consecutive patients.
AB  - BACKGROUND: Early detection of pancreatic carcinoma is difficult even with
      current diagnostic tools. Novel biomarkers and detection techniques are urgently
      needed. Telomerase activity is a promising diagnostic marker. However, the
      conventional telomeric repeat amplification protocol (TRAP) assay is not suitable
      for clinical application because of its complexity, time-consuming nature, and
      the effects of polymerase chain reaction (PCR) inhibitors in samples leading to
      difficulties in quantification. METHODS: The authors used a hybridization
      protection assay in combination with TRAP (TRAP/HPA) to investigate the effects
      of PCR inhibitors in pancreatic juice on quantification of telomerase activity.
      They analyzed 117 consecutive samples of pancreatic juice to determine the
      feasibility of TRAP/HPA for diagnosis of pancreatic carcinoma. RESULTS: The
      authors found that TRAP/HPA was 1000-fold more sensitive than the conventional
      TRAP assay, and that the effects of PCR inhibitors could be avoided by diluting
      samples. In a large analysis of pancreatic juice samples with TRAP/HPA, 17
      samples were excluded from the final analysis because of insufficient follow-up
      periods or inadequate treatment of the samples. Relative telomerase activity
      (RTA) in samples from patients with pancreatic carcinoma was significantly higher
      in comparison to samples from patients with pancreatitis and 13 (61.9%) of 21
      samples from patients with pancreatic carcinoma showed high RTA (> 4 U).
      Meanwhile, high RTAs were observed in 4 of 35 (11.4%) samples from patients with
      intraductal papillary mucinous tumor and in 1 of 40 samples (2.5%) fom patients
      without malignant disease. CONCLUSIONS: TRAP/HPA accurately evaluated weak
      telomerase activity in pancreatic juice samples without the problem due to PCR
      inhibitors. This large analysis of nonselected pancreatic juice samples suggested
      that TRAP/HPA is a promising approach for the diagnosis of pancreatic carcinoma.

PMID- 15476275
TI  - Type I collagen synthesis parallels the conversion of keratinocytic
      intraepidermal neoplasia to cutaneous squamous cell carcinoma.
AB  - Neoplastic progression of solid tumours is often characterized by a simultaneous
      increase in matrix protein (eg collagen) synthesis and degradation, and results
      in the formation of a tumour stroma. At the tumour periphery, this process is
      believed to facilitate angiogenesis and invasive growth of tumour cells. In
      various types of carcinoma, differentiation of fibroblasts towards myofibroblasts
      is thought to play an important role in extracellular matrix remodelling as their
      emergence coincides with architectural changes in the tumour stroma. Here,
      distinct architectural changes in collagen fibres are reported in cutaneous
      squamous cell carcinomas (cSCC) with respect to normal skin and precursor
      lesions, ie keratinocytic intraepidermal neoplasia (KIN). Simultaneously, type I
      collagen mRNA was observed in fibroblasts in close proximity to cSCC lesions
      (19/19) but only in 2 of 10 KIN lesions tested. Interestingly, whereas emerging
      of myofibroblasts correlated with reduced differentiation of cSCCs, it was not a
      prerequisite for type I collagen synthesis. These data indicate that type I
      collagen synthesis by fibroblasts parallels the malignant transformation of human
      KIN to cSCC.

PMID- 15476276
TI  - Preoperative somatic symptoms are associated with disease progression in patients
      with bladder carcinoma after cystectomy.
AB  - BACKGROUND: A link between patient psychologic factors and bladder carcinoma
      outcome has not been demonstrated. The purpose of the current study was to assess
      the association of psychologic factors measured preoperatively with bladder
      carcinoma progression after cystectomy. METHODS: The Brief Symptom Inventory
      (BSI)-18 was administered prospectively to 65 patients with clinically localized
      bladder carcinoma before surgery. The BSI-18 measures distress in three specific
      domains-depression, anxiety, and somatization (i.e., distress due to somatic
      symptoms)-as well as general distress. Preoperative BSI-18 scores, tumor
      pathologic stage, and certain clinical variables were compared with disease
      status. Disease progression was defined as the development of either local
      disease recurrence or distant metastasis. Univariate and multivariate Cox
      proportional hazards models were constructed for statistical analysis. RESULTS:
      Of the 65 patients, 49 (79.4%) had no evidence of disease, 4 (6.2%) had local
      disease recurrence, and 12 (18.5%) had metastatic disease at last follow-up. The
      mean follow-up time was 1.3 years and did not differ significantly between
      survival outcomes (P = 0.577). Both tumor pathologic stage and preoperative
      somatic distress scores were associated with time to disease progression by
      univariate analysis (P = 0.038 and P = 0.055, respectively). After adjusting for
      tumor pathologic stage, a somatic distress score of > or = 2.00 was a significant
      predictor of disease progression (P = 0.044, hazard ratio = 3.31, 95% confidence
      interval = 1.03-10.60). Patient age, gender, reconstruction type, and BSI-18
      scores for depression, anxiety, and general distress were not significantly
      associated with disease outcome. CONCLUSIONS: The authors found no correlation
      between psychologic symptoms measured preoperatively (i.e., depression, anxiety,
      and general distress) and bladder carcinoma progression. However, they reported
      an association between somatic symptoms and cancer outcome. If confirmed by other
      studies, these results may have important implications for the diagnosis,
      staging, and potential treatment of patients with bladder carcinoma.

PMID- 15476277
TI  - Cyclooxygenase-2 expression in experimental post-transplant obliterative
      bronchiolitis.
AB  - Epithelial cell injury, inflammation, progressive fibrosis, and airway
      obliteration are histological features of post-transplant obliterative
      bronchiolitis (OB). Cyclooxygenase (COX)-2 is expressed in acute and chronic
      inflammatory responses. Our aim was to elucidate the possible role of COX-2 in
      post-transplant OB by using a heterotopic bronchial porcine model. Bronchial
      allografts from non-related donors were transplanted subcutaneously into 24
      random-bred domestic pigs, each weighing about 20 kg. Groups studied had grafts,
      non-treated allografts, allografts given cyclosporine A (CsA), methylprednisolone
      (MP), and azathioprine (Aza), and allografts given CsA, MP, and everolimus.
      Grafts were serially harvested during a follow-up period of 21 days for histology
      (H&E) and immunohistochemistry. Immunostaining was performed with monoclonal IgG
      against human COX-2 peptide, and histological alterations and immunohistochemical
      positivity were graded on a scale from 0 to 5. Epithelial COX-2 index was
      calculated by multiplying the percentage of positive cells by grade of epithelial
      COX-2 intensity. Ischaemic epithelial loss, evident in all implants, recovered
      rapidly in autografts, and bronchi remained patent. Epithelial loss in non
      treated allografts preceded fibroblast proliferation, resulting in total luminal
      obliteration. In CsA-, MP-, and Aza-treated allografts epithelial destruction and
      luminal obliteration were delayed, and these were prevented in CsA-, MP-, and
      everolimus-treated allografts. COX-2 expression due to operative ischaemia was
      evident in all implants on day 2. Thereafter, the epithelial COX-2 index preceded
      epithelial injury and obliteration. During the inflammatory response and
      fibroblast proliferation, COX-2 expression occurred in macrophages and
      fibroblasts. In conclusion, in the early stage of OB development, COX-2 induction
      occurred in airway epithelial cells prior to luminal obliteration. In addition,
      the observation that COX-2 expression in macrophages and fibroblasts paralleled
      the onset of inflammation and fibroblast proliferation indicates a role in OB
      development, but the causal relationships need further study.

PMID- 15476278
TI  - Frequency and resolution dependence of the anisotropic impedance estimation in
      cortical bone using time-resolved scanning acoustic microscopy.
AB  - The influences of frequency and spatial resolution on the anisotropic impedance
      estimation of cortical bone was investigated in the frequency range 25-100 MHz. A
      set of spherically focused transducers provided a spatial resolution in the range
      from 150 down to about 20 mum. Four embedded cortical bone samples (two male, two
      female, two donors aged <30 years, two donors aged >70 years) were cut with
      different orientations relative to the long axis of the femur (0-90 degrees ).
      From each section, impedance maps were acquired in the C-scan mode. Histogram
      evaluations showed a similar angular dependence with a characteristic off-axis
      maximum of the estimated impedance for all samples and frequencies. The impedance
      values obtained with the 25-MHz transducer were significantly lower than those
      obtained with the 50- and 100-MHz transducers. Morphological parameters of the
      macrostructure, for example, size and distribution of the haversian channels and
      the resulting porosity, were estimated from the high-resolution acoustic images.
      These structures appeared to have a significant influence on the measured
      properties of the bone matrix for the low-frequency and low-aperture
      measurements.

PMID- 15476279
TI  - The prion protein in human neuromuscular diseases.
AB  - The basis of human prion diseases affecting the nervous system is accumulation of
      a disease-associated conformer (PrPSc) of the normal cellular prion protein
      (PrPC). Earlier studies demonstrated increased expression of PrPC in inclusion
      body myositis (IBM), dermato-, and polymyositis, as well as neurogenic muscle
      atrophy. To define the spectrum and reliability of PrPC immunoreactivity, its
      expression was examined systematically in a series of pathologically
      characterized muscular disorders by means of immunohistochemistry, confocal laser
      microscopy, and immunogold electron microscopy. Anti-PrPC immunolabelling of
      rimmed vacuoles was observed in IBM, inclusions of myofibrillary myopathy,
      targets, regenerating, and atrophic fibres, mononuclear cells, in addition to
      ragged red fibres in mitochondrial myopathies, and focal sarcolemmal
      immunostaining in non-diseased controls. Quantitative analysis demonstrated that,
      in neurogenic muscle lesions, anti-PrPC staining detects a significantly broader
      spectrum of fibres than anti-vimentin or anti-NCAM. In dystrophic muscle, PrPC
      expression was mainly restricted to regenerating fibres. In IBM, PrPC expression
      was not confined to rimmed vacuoles or vacuolated fibres and only a small
      percentage (7.1%) of rimmed vacuoles were PrPC positive. Ultrastructurally, PrPC
      was observed in the cytoplasm of lymphocytes, in the myofibrillar network of
      targets, and in rimmed vacuoles. Knowledge of disease circumstances with altered
      expression of PrPC is important in the setting of a potentially increased chance
      for extraneural PrPC-PrPSc conversion. In addition, our observations suggest that
      PrPC may have a general stress-response effect in various neuromuscular
      disorders.

PMID- 15476280
TI  - Pancreatic carcinoma cells express neuropilins and vascular endothelial growth
      factor, but not vascular endothelial growth factor receptors.
AB  - BACKGROUND: Neuropilins (NRPs) are characterized as coreceptors of vascular
      endothelial growth factor (VEGF). In the current study, the authors assessed the
      expression of NRPs, VEGF, and vascular endothelial growth factor receptors
      (VEGFRs), as well as VEGF-induced cell proliferation, in pancreatic carcinoma
      cell lines and tissue specimens. METHODS: Human pancreatic carcinoma cell lines
      (Panc-1 and MIA PaCa-2), normal human pancreatic ductal epithelial cells (HPDE),
      and human umbilical vein endothelial cells (HUVECs) were cultured. Human
      pancreatic adenocarcinoma tissue specimens were also studied. Expression levels
      of NRPs, VEGFRs, and VEGF were determined by real-time polymerase chain reaction
      analysis and immunostaining. Cell proliferation was examined using a
      [3H]thymidine incorporation assay. RESULTS: Both NRP-1 and NRP-2 were expressed
      in Panc-1 cells, HPDE cells, and HUVECs but were expressed minimally in MIA PaCa
      2 cells. Panc-1 expressed 30 times more NRP-1 mRNA than NRP-2 mRNA. NRP-1 levels
      in Panc-1 cells were 5.3 times higher than in HPDE cells but were similar to NRP
      1 levels in HUVECs. NRP-2 levels in Panc-1 cells were similar to NRP-2 levels in
      HPDE cells but lower than NRP-2 levels in HUVECs. Expression of all three VEGFRs
      was observed only in HUVECs. However, VEGF mRNA was detected in all cell types
      except for HUVECs. NRP-1 immunoreactivity levels were much higher than NRP-2
      immunoreactivity levels in Panc-1 and human pancreatic adenocarcinoma tissue
      specimens, whereas VEGFRs were not detected in either of these two settings. In
      response to VEGF165, [3H]thymidine incorporation in Panc-1 cells increased
      significantly (by 61%; P < 0.01). A monoclonal antibody against human NRP-1
      significantly blocked VEGF-induced cell proliferation in Panc-1 cells.
      CONCLUSIONS: The pancreatic carcinoma cell line Panc-1 and adenocarcinoma tissue
      specimens expressed high levels of NRP-1 and VEGF, but not VEGFRs, and exogenous
      VEGF significantly increased NRP-1-mediated, but not VEGFR-mediated, Panc-1 cell
      proliferation. These data suggested that NRP-1 may be involved in the
      pathogenesis of pancreatic carcinoma.

PMID- 15476281
TI  - Preclinical evaluation of antisense bcl-2 as a chemosensitizer for patients with
      gastric carcinoma.
AB  - BACKGROUND: Because bcl-2 is a critical factor for anticancer drug-induced
      apoptosis, the authors conducted a preclinical evaluation of antisense (AS) bcl-2
      as an enhancer of the chemotherapeutic effect in the treatment of patietns with
      gastric carcinoma. METHODS: AS bcl-2 was used with 18-mer phosphorothiated
      oligonucleotides in the MKN-45 gastric carcinoma cell line. Drug sensitivity in
      vitro was evaluated using the methyl-thiazoldiphenyl tetrazolium assay, and
      antitumor effects in vivo were evaluated using the nude mouse xenograft.
      Apoptosis was determined with the terminal deoxyuridine triphosphate nick-end
      labeling assay. AS bcl-2 in vitro was treated with lipofectin, whereas it was
      administered intraperitoneally for 6 consecutive days twice every 2 weeks in
      vivo. Anticancer drugs were administered intraperitoneally four times per week.
      RESULTS: bcl-2 was down-regulated to 60% of its initial value after treatment
      with 1.0 muM AS bcl-2 compared with the controls of random and mismatched
      oligonucleotides. Drug sensitivity to doxorubicin, cisplatin, and paclitaxel
      (TXL) was increased 3-4-fold when used in combination with AS bcl-2, which was
      determined with 50% inhibitory concentration values, compared with the control
      group. Increased drug sensitivity was associated with apoptosis, which increased
      in Bax and poly-adenosine diphosphate (ADP-ribose) polymerase and decreased in
      phosphorylated Akt (pAkt). The antitumor effect of cisplatin and TXL in vivo was
      enhanced significantly in combination with AS bcl-2. Down-regulation of bcl-2 was
      observed on Day 4 after the treatment with AS bcl-2. CONCLUSIONS: Combination
      treatment with AS bcl-2 and anticancer drugs, including cisplatin and TXL, may be
      a new strategy for enhancing chemotherapeutic effects in the treatment of gastric
      carcinoma.

PMID- 15476282
TI  - Adult glioma incidence trends in the United States, 1977-2000.
AB  - BACKGROUND: Several authors have reported an increase in the incidence of brain
      tumors, especially among the elderly. A more complete understanding of adult
      glioma incidence trends might provide indications of risk factors for gliomas and
      contribute to the search for improved therapies. METHODS: The authors used the
      Surveillance, Epidemiology, and End Results (SEER) registry public use data
      tapes, which included data on patients with cancer diagnosed between 1973 and
      2000. For 3 histologies as well as for 12 histology categories combined, the
      authors used Poisson regression to model incidence as a function of year of
      diagnosis, age at diagnosis, race (white or African American), and gender. They
      used cubic splines to fit age at diagnosis and year of diagnosis and tested for
      all pair-wise interactions. RESULTS: The interaction between year of diagnosis
      and age at diagnosis was significant in all four groups modeled. In glioblastoma,
      there was also a significant interaction between gender and age at diagnosis. In
      anaplastic astrocytoma, there was a significant interaction between gender and
      year of diagnosis. In oligodendroglioma, there was a significant interaction
      between race and gender. In the 12 histology categories combined, there was a
      significant interaction between gender and age at diagnosis. CONCLUSIONS: The
      results in the current study were consistent with other published reports that
      showed an increase in the incidence of brain tumors using SEER data. Although
      others have observed increasing incidence trends among the elderly, the authors
      formally tested and found a statistically significant interaction between age at
      diagnosis and year of diagnosis.

PMID- 15476283
TI  - Nuclear factor-kappaB and IkappaB kinase are constitutively active in human
      pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is
      associated with the suppression of proliferation and the induction of apoptosis.
AB  - BACKGROUND: Pancreatic carcinoma is a lethal malignancy, with the best available
      therapeutic option-gemcitabine-yielding response rates of < 10%. Because nuclear
      factor-kappaB (NF-kappaB) has been determined to play a role in cell
      survival/proliferation in human pancreatic carcinoma, this transcription factor
      is a potential therapeutic target. METHODS: The authors investigated the ability
      of curcumin (diferuloylmethane), an agent that is pharmacologically safe in
      humans, to modulate NF-kappaB activity. RESULTS: NF-kappaB and IkappaB kinase
      (IKK) were constitutively active in all human pancreatic carcinoma cell lines
      examined, and curcumin consistently suppressed NF-kappaB binding (as assessed
      using an electrophoretic mobility gel-shift assay) and IKK activity. Curcumin
      decreased the expression of NF-kappaB-regulated gene products, including
      cyclooxygenase-2 (as assessed using immunoblot analysis), prostaglandin E2, and
      interleukin-8 (as assessed using an enzyme-linked immunoassay), all of which have
      been implicated in the growth and invasiveness of pancreatic carcinoma. These
      changes were associated with concentration- and time-dependent antiproliferative
      activity (as assessed using a 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide [MTT] assay) and proapoptotic effects (as assessed
      via annexin V/propidium iodide staining [fluorescence-activated cell sorting, as
      well as with the induction of polyadenosine-5'-diphosphate-ribose polymerase
      cleavage). CONCLUSIONS: Curcumin down-regulated NF-kappaB and growth control
      molecules induced by NF-kappaB in human pancreatic cells. These effects were
      accompanied by marked growth inhibition and apoptosis. Through these findings,
      the authors provided a biologic rationale for the treatment of patients with
      pancreatic carcinoma using this nontoxic phytochemical.

PMID- 15476284
TI  - Synthesis and evaluation of some novel quinazolinone derivatives as diuretic
      agents.
AB  - A new series of quinazolin-4(3H)-one derivatives containing either a thiazole or
      a 1, 3, 4-thiadiazole moiety were prepared in order to study the effect of such a
      heterocyclic combination on the expected diuretic activity. Synthesis of the
      target compounds (2, 4, and 6) has been achieved through an interaction of the
      starting 7-chloro-2-methyl-4H-3, 1-benzoxazin-4-one 1 with different heterocyclic
      amines. Alkylation of 3-(2-mercapto-1, 3, 4-thiadiazol-5-yl)quinazolin-4(3H)-one
      derivative 4 with different alkyl halides or chloroacetic acid afforded the
      corresponding thioethers 5 while interaction of 2-methyl-3-(1, 3, 4-thiadiazol-5
      yl or thiazol-5-yl)quinazolin-4(3H)-ones (2 and 6) with various aromatic
      aldehydes resulted in the formation of the arylvinyl analogs 3 and 7,
      respectively. On the other hand, 2-morpholinomethyl-3-(2-sulfamoyl or mercapto-1,
      3, 4-thiadiazol-5-yl)quinazolin-4(3H)-one derivatives 10 have also been
      synthesized through an interaction of the sulfonamide or thiol analog 9 with the
      appropriate amine. Biological evaluation of some of the target compounds as
      diuretic agents was carried out. The results showed that 2-[2-(4
      chlorophenyl)vinyl]-7-chloro-3-(2-sulfamoyl-1, 3, 4-thiadiazol-5-yl)quinazolin
      4(3H)-one 7b exhibited significant diuretic activity. The detailed synthesis,
      spectroscopic and biological data are reported.

PMID- 15476285
TI  - Search for histamine H(3) receptor ligands with combined inhibitory potency at
      histamine N-methyltransferase: omega-piperidinoalkanamine derivatives.
AB  - In an effort to design new hybrid compounds with dual properties, i.e. binding
      affinity at histamine H(3) receptors and inhibitory potency at the catabolic
      enzyme histamine N(tau)-methyltransferase (HMT), a novel series of 1-substituted
      piperidine derivatives was synthesized. This alicyclic heterocycle is
      structurally linked via aminoalkyl spacers of variable lengths to additional
      aromatic carbo- or hetero-cycles. These new hybrid drugs were pharmacologically
      evaluated regarding their binding affinities at recombinant human H(3) receptors,
      stably expressed in CHO cells, and in a functional assay for their inhibitory
      potencies at rat kidney HMT. All compounds investigated proved to be H(3)
      receptor ligands with binding affinities in the micro- to nanomolar concentration
      range despite significant differences in the type of the aromatic moiety
      introduced. The most potent compound in this series was the quinoline derivative
      20 (K(i) = 5.6 nM). Likewise, all new ligands studied showed impressive HMT
      inhibitory activities. Here, compounds 5, 10, 14 and 18-20 exhibited
      submicromolar potencies (IC(50) = 0.061-0.56 microM). The aminomethylated
      quinoline 19 showed almost the same, well balanced nanomolar activities on both
      targets. In this study, new hybrid compounds with a dual mode biological action
      were developed. These pharmacological agents are valuable leads for further
      development and candidates for treatment of histamine-dependent disorders.

PMID- 15476286
TI  - Practical synthesis of fenbufen ethanolamide.
AB  - The ongoing interest in ethanolamide derivatives of anti-inflammatory drugs as
      potential synthetic cannabinoids and mechanistic tools for the study of
      cannabinoid and vanilloid receptors prompted us to develop a practical gram scale
      synthesis for the hitherto unknown ethanolamide of fenbufen. Dehydration of
      fenbufen leads to intramolecular ring closure yielding bright pink crystals of
      the intramolecular enol ester. Reaction of this activated but stable intermediate
      with ethanolamine leads to the title compound in good yield and purity without
      the necessity to remove coupling reagents or residual activating groups, such as
      N, N-dialkyl ureas and fluorinated phenols.

PMID- 15476287
TI  - Synthesis and antimycobacterial activity of pyridylmethylsulfanyl and
      naphthylmethylsulfanyl derivatives of benzazoles, 1, 2, 4-triazole, and pyridine
      2-carbothioamide/-2-carbonitrile.
AB  - A set of four types of benzazoles, 1, 2, 4-triazole, and pyridine-2-carbonitrile/
      2-carbothioamide substituted with 1-naphthylmethylsulfanyl or
      pyridylmethylsulfanyl was prepared to modify the structure of benzylsulfanyl
      derivatives of the above-mentioned heterocycles. The compounds were evaluated for
      in vitro antimycobacterial activity against Mycobacterium tuberculosis, M. avium,
      and two strains of M. kansasii. The activities were expressed as the minimum
      inhibitory concentration (MIC). The MIC values fall into a range of 2 to >1000
      micromol/L. Introduction of a pyridyl moiety into the molecule mostly decreased
      the activity. A naphthyl moiety did not influence the activity in comparison with
      a phenyl. The most active substances were 4-(3-pyridylmethylsulfanyl)pyridine-2
      carbothioamide (7b) (MIC = 2 - >62.5 micromol/L) and 4-(1
      naphthylmethylsulfanyl)pyridine-2-carbothioamide (7d) (MIC = 2 - >32 micromol/L).

PMID- 15476288
TI  - Synthesis and potent antimicrobial activity of some novel 4-(5, 6-dichloro-1H
      benzimidazol-2-yl)-N-substituted benzamides.
AB  - A series of 4-(5, 6-dichloro-1H-benzimidazol-2-yl)-N-substituted benzamides were
      synthesized and evaluated for antibacterial and antifungal activities against
      Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), methicillin
      resistant S. epidermis (MRSE), Enterococcus faecalis, Escherichia coli and
      Candida albicans. Certain compounds inhibit bacterial growth with low MIC values
      (microg/mL). Among them, compounds 10 and 11 exhibited the greatest antibacterial
      activity with MIC values of 3.12 microg/mL against S. aureus, MRSA and MRSE.

PMID- 15476289
TI  - Application of NMR screening techniques for observing ligand binding with a
      protein receptor.
AB  - Water ligand observed via gradient spectroscopy (WaterLOGSY), saturation transfer
      difference and NOE pumping NMR techniques were used to identify ligand binding
      with a receptor. Although these experiments were originally designed to observe
      ligands in complexes, their application is limited by the affinity of ligands
      towards target molecules. Here the improved WaterLOGSY pulse sequence was
      developed by incorporating the double pulsed field gradient spin-echo and
      gradient-tailored excitation WATERGATE sequences. The efficiency of these ligand
      observed NMR screening techniques was investigated using the ribonuclease T1
      inhibitor system.

PMID- 15476290
TI  - Myoepithelial cell-rich neoplasms: cytologic features of benign and malignant
      lesions.
AB  - BACKGROUND: Lesions that contain abundant myoepithelial cells may present as a
      diagnostic challenge in fine-needle aspiration (FNA) specimens. Potential
      diagnostic problems may arise due to morphologic heterogeneity of myoepithelial
      cell-rich lesions and difficulty in predicting malignancy in FNA specimens. An
      accurate diagnosis is important, because malignant myoepithelial cell-rich
      lesions require a wider local excision and lymph node dissection. The authors
      characterized the cytologic features of myoepithelial cell-rich lesions in an
      attempt to define the criteria that facilitate distinction between benign and
      malignant tumors. METHODS: FNA biopsies of myoepithelial cell-rich lesions with
      corresponding histologic specimens were selected. The cytology specimens were
      evaluated for the following criteria: cellularity, cell morphology, pleomorphism,
      chromatin pattern, presence of nucleoli, background material, necrotic debris,
      and presence of mitotic figures. A review of the histologic sections was
      performed for diagnostic confirmation. RESULTS: Seventeen specimens from 17
      different patients were selected. The histologic diagnoses were myoepithelial
      carcinoma (n = 6 patients), malignant mixed tumor with predominant myoepithelial
      carcinoma (n = 2 patients), epithelial-myoepithelial carcinoma (n = 1 patient),
      and benign mixed tumor (n = 8 patients). The primary sites included the parotid
      gland (n = 10 patients), submandibular gland (n = 3 patients), minor salivary
      gland (n = 3 patients), and breast (n = 1 patient). Most specimens, whether they
      were benign or malignant, were very cellular. Pleomorphism, coarse chromatin,
      prominent nucleoli, mitotic figures, and necrosis were observed only in malignant
      specimens. Background material and ductal cells were seen in both benign and
      malignant specimens. CONCLUSIONS: The presence of pleomorphism, coarse chromatin,
      prominent nucleoli, mitotic figures, and/or necrosis should raise the possibility
      of myoepithelial carcinoma in FNA specimens from myoepithelial cell-rich lesions.

PMID- 15476291
TI  - Rat-PET study without anesthesia: anesthetics modify the dopamine D1 receptor
      binding in rat brain.
AB  - Positron emission tomography (PET) measurements in 6-month-old F344/N rats were
      performed in the conscious state and the influence of chloral hydrate, ketamine,
      and pentobarbital anesthesia on dopamine D(1) (DA-D(1)) receptor binding was
      evaluated using [(11)C]SCH23390, a selective DA-D(1) receptor ligand. To perform
      the PET study in conscious rats, an original fixation apparatus was developed and
      the animals were trained to acclimate to the scanning atmosphere for 3 h. This
      training was carried out twice a day for 2 weeks. PET measurements in conscious
      rats were successful, since the trained rats scarcely moved during the scanning
      (as monitored by video camera) and since highly reproducible measurements of
      binding potential (BP) were derived from their scanning. Chloral hydrate and
      ketamine anesthesia significantly increased the striatal BP of DA-D(1) receptors
      by 36% and 46%, respectively, compared to that observed in the conscious state.
      In contrast, pentobarbital markedly decreased the BP by 41%. These BP values of
      DA-D(1) receptors were calculated using a curve-fitting method. Our results
      indicate that PET studies in rats should be performed in the conscious state
      since the anesthetics dramatically modified ligand-receptor bindings, such as DA
      D(1) receptor binding, in rat brain.

PMID- 15476292
TI  - The tautomerism of 1H-pyrazole-3(5)-(N-tert-butyl)carboxamide in the solid state
      and in solution.
AB  - The X-ray crystal structure of 1H-pyrazole-3-(N-tert-butyl)-carboxamide was
      determined. In the solid state, the 13C and 15N CP/MAS NMR spectra correspond to
      this tautomer. In solution, both tautomers are present in a ratio that depends on
      the temperature (at 293 K, 90% 3-substituted/10% 5-substituted). Some unusual 1H,
      1H couplings involving the NH proton were observed. DFT (GIAO) calculations were
      carried out.

PMID- 15476293
TI  - Low-mode docking search in iGluR homology models implicates three residues in the
      control of ligand selectivity.
AB  - Homology models of the ionotropic rat kainate receptor iGluR6, based on the
      ligand binding domains of iGluR2, were constructed. A systematic analysis by low
      mode docking searches of kainic acid in homology models of the native iGluR6
      receptor, chimeric (iGluR2 and iGluR6) receptors and mutant receptors have
      identified three residues which influence the conformation of kainic acid in the
      binding core and hence the affinity for kainic acid. These residues are Leu650,
      Thr649 and Leu704, all located in domain 2. Leu650 has previously been implicated
      in the control of selectivity of iGluR2. However, this is the first report that
      suggests that Thr649 and Leu704 play a role in receptor selectivity.

PMID- 15476294
TI  - RNase S complex bearing arginine-rich peptide and anti-HIV activity.
AB  - Basic peptide-mediated protein delivery into living cells is becoming recognized
      as a potent approach for the understanding of cellular mechanisms and drug
      delivery. We have prepared the conjugates of the S-peptide (1-15) derived from
      RNase S with membrane-permeable basic peptides, octaarginine and the human
      immunodeficient virus (HIV)-1 Rev (34-50). The RNase S complexes, formed among
      these S-peptide (1-15)-basic peptide conjugates and the S-protein and having a
      dissociation constant in the range of 10(-5) M, efficiently penetrated into the
      HeLa cells. These RNase S complexes exerted an anti-HIV replication activity. The
      time-of-drug-addition assay suggested that the site of action for these complexes
      would reside in the stages between the viral entry into the cells and reverse
      transcription. The present study exemplified the applicability of the arginine
      rich peptides to the intracellular targeting of non-covalent protein complexes
      and supramolecular assemblies for the research in chemical and cellular biology.

PMID- 15476295
TI  - Sonography of fetal micturition.
AB  - OBJECTIVE: To describe the sonographic visualization of fetal micturition and its
      role in the diagnosis of posterior urethral valves and hypospadias. METHODS: This
      was a prospective study of 25 male fetuses (21 with bilateral pyelectasis, one
      whose bladder was being studied because of ureterocele and three with
      hypospadias), and five female fetuses (with bilateral pyelectasis). A midline
      sagittal scan of the fetal pelvis, perineum and external genitalia was obtained
      and observed continuously during fetal micturition. RESULTS: In 19 of the 21 male
      fetuses and the five female fetuses with bilateral pyelectasis micturition was
      normal, with visualization of urinary bladder contraction, slight fluid
      distention of the urethra and a urinary stream from the external urethral meatus.
      In three male fetuses, two with bilateral pyelectasis and the one with
      ureterocele, the posterior urethra was normal at rest and it ballooned out during
      micturition, diagnostic of posterior urethral valves. In the three male fetuses
      with hypospadias the ventral jet of the urinary stream was visualized.
      CONCLUSION: Fetal micturition can be visualized on sonography. It may be of value
      in the diagnosis of posterior urethral valves and hypospadias.

PMID- 15476296
TI  - Spontaneous ovarian hyperstimulation syndrome and hyperreactio luteinalis are
      entities in continuum.
AB  - Hyperreactio luteinalis (HL) and spontaneous ovarian hyperstimulation syndrome
      (OHSS) are both rare conditions during pregnancy. The clinical presentation of HL
      and OHSS are comparable and both should be differentiated from ovarian carcinoma.
      We present a case of a 32-year-old woman who was initially seen with markedly
      enlarged multicystic ovaries and ascites in the 13th week of a spontaneously
      conceived pregnancy. Ultrasonographic follow-up and magnetic resonance imaging of
      the ovaries were employed in order to avoid exploratory laparotomy and rule out
      ovarian carcinoma. The patient received supportive therapy and delivered a
      healthy child at term. The increasing use of ultrasonography may lead to more
      frequent findings of multicystic ovaries in spontaneously conceived pregnancies.
      Making the distinction between HL and spontaneous OHSS in these cases may be
      difficult though clinically irrelevant as the approach to treatment is similar in
      both.

PMID- 15476297
TI  - A new formula for calculating weight in the fetus of < or = 1600 g.
AB  - OBJECTIVE: To develop and test a new formula for estimating weight in the fetus
      of < or = 1600 g. METHODS: A formula for sonographic estimation of fetal weight
      was produced retrospectively from 84 singleton fetuses with a birth weight of <
      or = 1600 g, examined sonographically within 1 week before delivery. Exclusion
      criteria were multiple pregnancy, intrauterine death and major structural or
      chromosomal anomalies. The new formula was then compared prospectively in an
      evaluation group of fetuses (n = 87) with six currently available equations for
      estimating weight in the preterm fetus. RESULTS: Stepwise regression analysis
      with gestational age (in days) and fetal biometric parameters was employed to
      yield the best-fit formula for predicting fetal weight at birth. The new formula
      (estimated fetal weight = 5381.193 + 150.324 x head circumference + 2.069 x femur
      length3 + 0.0232 x abdominal circumference3-6235.478 x log(head circumference))
      proved to be superior to established equations. The lowest mean +/- SD absolute
      error was 66.2 +/- 59 g and the lowest mean absolute percentage error was 7.1 +/-
      5.9% SD when studied prospectively in the evaluation group. With the new formula,
      48.3% of estimates fell within +/-5% of the actual weight at birth, 73.6% fell
      within +/-10%, 90.8% fell within +/-15% and 95.4% fell within +/-20%. CONCLUSION:
      Our new formula is relatively easy to use and needs no adjustment to weight
      centiles or to fetal lie. It allows reliable weight estimation in the fetus < or
      = 1600 g.

PMID- 15476298
TI  - Preoperative diagnosis of colouterine fistula secondary to diverticulitis by
      sonohysterography with contrast medium.
AB  - Colouterine fistulae secondary to sigmoid diverticulitis are unusual. Methods for
      diagnosis remain to be established. We report a case with a colouterine fistula
      in which sonohysterography detected the flow of ultrasound contrast medium
      between the uterine cavity and the sigmoid colon through the posterior uterine
      wall, thus confirming the diagnosis. The diagnosis was further substantiated by a
      charcoal challenge test. The patient underwent en bloc resection of the uterus,
      Fallopian tubes, ovaries and sigmoid colon, the organs involved with
      diverticulitis. This is the first report to describe a colouterine fistula
      successfully diagnosed by sonohysterography using ultrasound contrast medium.

PMID- 15476299
TI  - Transvaginal sonographic diagnosis of a tumor fistula.
AB  - We report on two cases of advanced pelvic cancer in women who presented with
      profuse vaginal watery discharge. In both cases, transvaginal ultrasound revealed
      a fistulous tract connecting the tumor to the apex of the vaginal vault. The
      differential diagnoses and a review of the literature are discussed.

PMID- 15476300
TI  - Intraobserver and interobserver reproducibility of fetal biometry.
AB  - OBJECTIVE: To assess the intra- and interobserver reproducibility of ultrasound
      measurements of fetal biometric parameters. METHODS: We assessed the
      intraobserver and the interobserver agreement in measurements of fetal biparietal
      diameter (BPD), abdominal circumference (AC), head circumference (HC) and femur
      length (FL) on 122 singleton pregnancies. Patients were each examined twice by
      the first sonographer to determine the intraobserver reliability of measurements
      of fetal biometry. Subsequently, during the same ultrasound examination, a second
      blinded sonographer measured fetal biometric parameters to assess interobserver
      reliability. The consensus between and among observers was analyzed using the
      intraclass correlation coefficient (intra-CC) and interclass correlation
      coefficient (inter-CC) and the reliability coefficients (RC, alpha) for the four
      biometric measurements. A value > 0.75 was considered a reliable consensus for
      the intra-CC and inter-CC. A Bland and Altman plot was also created for the fetal
      biometric parameters to assess the repeatability of the measurements. RESULTS:
      Reliable consensus was observed for both the intra-CC and inter-CC and RC for all
      four biometric parameters. The intra-CC with the 95% CI and RC for the BPD, AC,
      HC and FL were as follows: 0.996 (0.995, 0.997), alpha 0.998; 0.994 (0.992,
      0.996), alpha 0.997; 0.996 (0.994, 0.997), alpha 0.998; and 0.994 (0.992, 0.996),
      alpha 0.997, respectively. Similarly, the inter-CC with the 95% CI and RC for the
      same parameters were as follows: 0.995 (0.993, 0.997), alpha 0.998; 0.980 (0.971,
      0.990), alpha 0.990; 0.994 (0.992, 0.996), alpha 0.997; and 0.990 (0.985,0.993),
      alpha 0.995, respectively. The Bland and Altman plots demonstrated a high degree
      of repeatability of BPD, AC, HC, and FL measurements. CONCLUSION: Our results
      demonstrate that the intra- and interobserver reproducibility of ultrasound
      measurements of fetal biometry are highly reliable.

PMID- 15476301
TI  - Antimicrobial evaluation of some medicinal plants for their anti-enteric
      potential against multi-drug resistant Salmonella typhi.
AB  - Screening was done of some plants of importance in the Ayurvedic system of
      traditional medicine used in India to treat enteric diseases. Fifty four plant
      extracts (methanol and aqueous) were assayed for their activity against multi
      drug resistant Salmonella typhi. Strong antibacterial activity was shown by the
      methanol extracts of Aegle marmelos, Salmalia malabarica, Punica granatum,
      Myristica fragrans, Holarrhena antidysenterica, Terminalia arjuna and Triphal
      (mixture of Emblica of fi cinalis, Terminalia chebula and Terminalia belerica).
      Moderate antimicrobial activity was shown by Picorhiza kurroa, Acacia catechu,
      Acacia nilotica, Cichorium intybus, Embelia ribes, Solanum nigrum, Carum
      copticum, Apium graveolens, Ocimum sanctum, Peucedanum graveolens and Butea
      monosperma.

PMID- 15476302
TI  - The antibacterial principle of Caesalpina sappan.
AB  - Using a bioassay-directed purification scheme, the active antibacterial principle
      from Caesalpina sappan was isolated and identified to be brasilin. This compound
      showed potent activity against antibiotic-resistant bacteria, notably methicillin
      resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci
      (VRE), multi-drug resistant Burkholderia cepacia as well as a number of other
      bacteria. The minimal inhibitory concentrations ranged from 4 to 32 microg/mL.
      The results from time-kill studies showed that brasilin is bactericidal against
      MRSA. The addition of brasilin to growing MRSA cells resulted in a rapid
      inhibition of incorporation of [(3)H] thymidine or [(3)H] serine into DNA and
      proteins, respectively. Exposure of MRSA to a sub-MIC level of brasilin for ten
      consecutive subcultures did not induce resistance to the compound. The Trypan
      blue dye exclusion test showed that brasilin lacked cytotoxicity against Vero
      cells. In conclusion, brasilin is an antibacterial principle from C. sappan and
      it has the potential to be developed into an antibiotic.

PMID- 15476303
TI  - Investigation of fractions present in the stem bark of Annickia kummeriae on
      their P-glycoprotein inhibitory pump activity.
AB  - Using MCF-7R cells and rhodamine 6G as the fluorescent probe, a bioassay-targeted
      purification process was pursued in order to isolate the active P-gp inhibitory
      fractions from Annickia kummeriae. Of 24 fractions obtained in the first
      preparative liquid chromatography (p-LC) run, only fraction 1 exhibited activity.
      Further p-LC fractionation led to the separation of fraction 1 into fractions 1.1
      1.8. Fractions 1.4, 1.5 and 1.6 proved to be active by inducing a significant
      accumulation of rhodamine 6G by 3.3-, 4.5- and 4.9-fold at 10 microg/mL, and by
      5.3-, 6.3- and 6.8-fold at 100 microg/mL, respectively. Fraction 1.6 was
      separated into several fractions by using an analytical liquid chromatography (a
      LC) system. Fractions 1.6.18, 1.6.19 and 1.6.20 were active and they induced an
      accumulation of rhodamine 6G by 3.0-, 1.8- and 3.5-fold at 1x microg/mL and by
      4.8-, 6.7- and 6.8-fold at 10x microg/mL, respectively. Afterwards, 28.3 mg of
      fraction 1.6 was processed by a-LC, and fractions 1.6.18, 1.6.19 and 1.6.20 were
      collected separately and dried. The amounts of materials recovered were 6.2, 7.4
      and <1 mg, corresponding to 21.9%, 26.1% and <3.5% of fraction 1.6, respectively.
      From the total amount injected and the relative masses represented by these
      fractions, it can be calculated that the 1x microg/mL level corresponded to ca.
      35, 42 and <5 microg/mL, respectively. Fluorescence microscopy revealed that
      incubation of the cells with rhodamine 6G alone did not show any fluorescence,
      whereas cells which were incubated in medium containing rhodamine 6G together
      with fraction 1.4, 1.6 or reserpine, clearly indicated accumulation of the dye
      intracellularly. This is an indication that the active compounds effected high
      intracellular fluorescence by inducing accumulation of the dye in the cells
      through inhibition of the P-gp pump.

PMID- 15476304
TI  - Antimalarial activity of Bidens pilosa L. (Asteraceae) ethanol extracts from wild
      plants collected in various localities or plants cultivated in humus soil.
AB  - Bidens pilosa (Asteraceae), a medicinal plant used worldwide, has antimalarial
      activity as shown in previous work. This study tested ethanol extracts from wild
      plants collected in three different regions of Brazil and from plants cultivated
      in various soil conditions. The extracts were active in mice infected with P.
      berghei: doses of < or =500 mg/kg administered by oral route reduced malaria
      parasitaemia and mouse mortality; higher doses were found to be less effective.
      Tested in vitro against three P. falciparum isolates, two chloroquine resistant
      and one mefloquine resistant, the plants cultivated under standard conditions,
      and in humus enriched soil, were active; but the wild plants were the most
      active. Analysis using thin layer chromatography demonstrated the presence of
      flavonoids (compounds considered responsible for the antimalarial activity) in
      all plants tested, even though at different profiles. Because B. pilosa is proven
      to be active against P. falciparum drug-resistant parasites in vitro, and in
      rodent malaria in vivo, it is a good candidate for pre-clinical tests as a
      phytotherapeutic agent or for chemical isolation of the active compounds with the
      aim of finding new antimalarial drugs.

PMID- 15476305
TI  - Oxygen activation by photoexcited protoberberinium alkaloids from Mahonia
      aquifolium.
AB  - Protoberberinium salts, i.e. berberine (I), palmatine (II) and jatrorrhizine
      (III) prepared from Mahonia aquifolium (Pursh) Nutt. belong to isoquinoline
      alkaloids possessing interesting biological activity (e.g. antibacterial,
      antimalarial, antitumor). The characteristic UV/Vis absorption band maxima of I
      III iodide salts were found in regions 350 and 425 nm in dimethylsulfoxide (DMSO)
      and ethanol solvents, and were only negligibly influenced by substitution changes
      on the C-2 and C-3 positions. The fluorescence intensity of protoberberinium
      salts monitored in ethanol solutions was significantly lowered by iodide counter
      ions, and decreased in the order berberine > palmatine > jatrorrhizine. EPR
      spectroscopy supplied evidence of the formation of super-oxide anion radicals and
      singlet oxygen upon irradiation of berberine in oxygenated DMSO solvent. The
      photochemical generation of O(2) (.-) and (1)O(2) in DMSO solutions of palmatine
      and jatrorrhizine was substantially lower, and probably reflected the replacement
      of a photolabile methylenedioxy group at C-2 and C-3 positions in the berberine
      molecule by two methoxy groups in palmatine, and methoxyl (C-2) and hydroxyl (C
      3) substitution in jatrorrhizine. Additionally, the powder EPR spectra of
      protoberberinium iodides I-III measured at 290 K revealed the presence of single
      line EPR signals (g(eff) = 2.0044), which were attributed to hydroperoxidic
      structures produced by the autoxidation process. The photochemical reactions of
      protoberbenium salts producing reactive oxygen species after UVA excitation
      should be integrated in biological activity investigations, as well as in their
      applications in skin disorder treatment.

PMID- 15476306
TI  - In vitro anti-beta-secretase and dual anti-cholinesterase activities of Camellia
      sinensis L. (tea) relevant to treatment of dementia.
AB  - The primary target of licensed drugs for the treatment of Alzheimer's disease is
      the inhibition of the enzyme acetylcholinesterase, although preventing beta
      amyloidosis is a prime target for drugs in development. The in vitro dual anti
      cholinesterase and beta-secretase activities of Camellia sinensis L. extract
      (tea) is reported. Green and black tea inhibited human acetylcholinesterase
      (AChE) with IC(50) values of 0.03 mg/mL and 0.06 mg/mL respectively, and human
      butyrylcholinesterase (BuChE) with IC(50) values 0.05 mg/mL. Green tea at a final
      assay concentration of 0.03 mg/mL inhibited beta-secretase by 38%. These novel
      findings suggest that tea infusions contain biologically active principles,
      perhaps acting synergistically, that may be used to retard the progression of the
      disease assuming that these principles, yet to be identified, reach the brain.

PMID- 15476307
TI  - Potent antioxidative and antigenotoxic activity in aqueous extract of Japanese
      rice bran--association with peroxidase activity.
AB  - To estimate the preventive potential of Japanese rice bran (Oryza sativa
      japonica) against the oxygen radical-related chronic diseases such as cardio
      vascular diseases and cancer, antioxidative and antigenotoxic activities of the
      rice bran extracts were analyzed by using assay systems for lipid peroxidation
      and genotoxin-induced umu gene expression. When effects of the rice bran extracts
      under different extraction conditions on hydroperoxide generation from auto
      oxidized linoleic acid were examined using aluminum chloride method, the water
      extract showed strong antioxidant activity, but the methanol and acetone extracts
      did not exhibit significant activity. The water extract of rice bran was divided
      into the ethanol-precipitable (EP) and supernatant fractions, and EP fraction
      showed the dominant antioxidant activity, but the supernatant fraction did not
      exhibit significant antioxidant activity. When the effect of EP fraction on umu C
      gene expression in SOS response associated with DNA damage in Salmonella
      typhimurium (TA 1535/pSK 1002) induced by 3-amino-1,4-dimethyl-5H-pyrido[4,3
      b]indole (Trp-P-1) was analyzed, it showed a dose-dependent suppressive activity
      against Trp-P-1-induced umu C gene expression. The bio-chemical analysis of EP
      fraction indicates that the major antioxidative and antigenotoxic activity of EP
      fraction is associated with a proteinous component with the molecular weight of
      more than 30 KDa. As a possible active principle for the antioxidative and
      antigenotoxic activity in EP fraction, the strong activity of an oxygen radical
      scavenging enzyme, peroxidase was detected, and the purified horseradish
      peroxidase also caused the similar antioxidative and antigenotoxic activities.
      The significance of this finding is discussed from the viewpoint of the
      preventive role of rice bran against oxygen radical-related chronic diseases.

PMID- 15476308
TI  - Identification of the antibacterial component of an ethanolic extract of the
      Australian medicinal plant, Eremophila duttonii.
AB  - Activity-guided fractionation was used to determine the antibacterial component
      of an ethanolic extract of the leaves of an Australian native medicinal plant,
      Eremophila duttonii F. Muell. (Myoporaceae). The extract, previously shown to
      have activity against Gram positive bacteria, was shown to have activity against
      additional Gram positive bacteria, including Clostridium perfringens, C.
      sporogenes and Listeria monocytogenes. Thin layer chromatography (TLC) was used
      to separate the extract into seven coloured fractions in visible light, one of
      which was shown by bioautography to contain antibacterial activity. Recovery of
      the component from the TLC plate and testing for antibacterial activity using a
      plate-hole diffusion assay supported this result. The purity of the component was
      verified by high-performance liquid chromatography and a time-kill experiment
      indicated that the purified component showed identical bactericidal activity to
      the whole extract. TLC spray reagents indicated that the component was a sterol,
      terpene or sugar but not a flavonoid, while the pigmented nature suggested a
      carotenoid.

PMID- 15476309
TI  - Polyherbal extract of septilin protects mice against whole body lethal dose of
      gamma radiation.
AB  - The effect of various doses (5, 10, 20, 40, 60, 80, 100, 120, 140 and 160 mg/kg
      b. wt.) of 50% ethanolic extract of Septilin (a herbal preparation) was studied
      on the radiation-induced mortality in mice exposed to 10 Gy of gamma-irradiation.
      Treatment of mice with different doses of Septilin, consecutively for 5 days
      before irradiation, delayed the onset of mortality and reduced the symptoms of
      radiation sickness when compared with the non-drug treated irradiated controls.
      All doses of Septilin provided protection against gastrointestinal (GI) deaths
      (death within 10 days of irradiation). However, the best protection was observed
      at 100 mg/kg b. wt. of Septilin, as the number of survivors after 30 days post
      irradiation was highest (58.33%) in this group when compared with the other doses
      of Septilin. The number of survivors was 1.75 fold greater for 100 mg/kg Septilin
      when compared with the 2-mercaptopropionylglycine (MPG, 33.33%) which was used as
      a positive control. The LD(50) of Septilin was 1250 mg/kg as against the optimum
      protective dose of 100 mg/kg. Our study demonstrates Septilin as a good
      radioprotective agent.

PMID- 15476310
TI  - Evaluation of the analgesic, anti-inflammatory and anti-diabetic properties of
      Sclerocarya birrea (A. Rich.) Hochst. stem-bark aqueous extract in mice and rats.
AB  - In order to appraise some of the ethnomedical uses of Sclerocarya birrea (A.
      Rich.) Hochst., subspecies caffra (Sond.) Kokwaro [family: Anacardiaceae], the
      present study was undertaken to investigate the analgesic, anti-inflammatory and
      anti-diabetic properties of the plant's stem-bark aqueous extract in experimental
      models of pain, inflammation and diabetes mellitus. The analgesic effect of
      Sclerocarya birrea stem-bark aqueous extract was evaluated in mice, while its
      anti-inflammatory and anti-diabetic effects were investigated in rats. Diclofenac
      (DIC, 100 mg/kg p. o.) and chlorpropamide (250 mg/kg p. o.) were used
      respectively as reference analgesic, anti-inflammatory and anti-diabetic agents
      for comparison. Like diclofenac (DIC, 100 mg/kg p. o.), Sclerocarya birrea stem
      bark aqueous extract (SBE, 100-800 mg/kg p. o.) produced dose-dependent,
      significant protection (p < 0.05-0.001) against electrical heat-induced pain. The
      plant extract (SBE, 25-800 mg/kg p. o.) also produced dose- and time-related,
      sustained and significant reductions (p < 0.05-0.001) in the fresh egg albumin
      induced acute inflammation of the rat hind paw oedema. However, the analgesic and
      anti-inflammatory effects of the plant's extract were found to be approximately
      10-15 times less than that of diclofenac. In one set of experiments involving
      hypoglycaemic/antidiabetic evaluation of the plant's extract, graded doses of
      Sclerocarya birrea stem-bark aqueous extract (SBE, 25-800 mg/kg p. o.) were
      separately administered to groups of fasted normal and fasted diabetic rats. In
      another set of experiments, a single dose of the plant's aqueous extract (SBE,
      800 mg/kg p. o.) was used. The hypoglycaemic effect of this single dose of
      Sclerocarya birrea stem-bark aqueous extract (SBE, 800 mg/kg p. o.) was compared
      with that of chlorpropamide (250 mg/kg p. o.) in both fasted normal and fasted
      streptozotocin (STZ)-treated diabetic rats. Following acute treatment, relatively
      moderate to high doses of Sclerocarya birrea stem-bark aqueous extract (SBE, 25
      800 mg/kg p. o.) produced dose-dependent, significant reductions (p < 0.05-0.001)
      in the blood glucose concentrations of both fasted normal and fasted diabetic
      rats. Chlorpropamide (250 mg/kg p. o.) also produced significant reductions (p <
      0.05-0.001) in the blood glucose concentrations of the fasted normal and fasted
      diabetic rats. Administration of the single dose of Sclerocarya birrea stem-bark
      aqueous extract (SBE, 800 mg/kg p. o.) significantly reduced (p < 0.01-0.001) the
      blood glucose levels of both fasted normal (normoglycaemic) and fasted STZ
      treated, diabetic rats. The results of this experimental animal study indicate
      that Sclerocarya birrea stem-bark aqueous extract possesses analgesic, anti
      inflammatory and hypoglycaemic properties. These experimental findings lend
      pharmacological support to the suggested folkloric uses of the plant's stem-bark
      in the management and/or control of pain, inflammatory conditions, and adult
      onset, type-2 diabetes mellitus in some communities of South Africa.

PMID- 15476311
TI  - Flavanoid of Drynaria fortunei protects against gentamicin ototoxicity.
AB  - A flavanoid fraction (FF) from Drynaria fortunei, was investigated to see if it
      has the protective and ameliorative effects against gentamicin (GM) ototoxicity
      in guinea pigs (n = 36). Eleven (GM-group) animals received GM 100 mg/kg/day.
      Eleven (GMFF-group) animals received the same dose of GM but 2 days prior were
      dosed with FF (10 mg/kg/day) for 2 weeks. Seven (S-group) animals received saline
      and seven (FF-group) animals received the same dose of FF as the GMFF-group. The
      thresholds of tone-burst auditory evoked response (ABR) at 2 k, 8 k, and 32 k Hz
      were determined to be as follows: GM-group: 90 dB, 92 dB and 72 dB, GMFF-group:
      30 dB, 37 dB and 38 dB, FF-group: 28 dB, 25 dB and 29 dB, S-group: 30 dB, 28 dB
      and 39 dB. The GM-group had a significantly higher hearing threshold than the
      other groups (p < 0.05). The GMFF- and FF-groups had hearing thresholds similar
      to the S-groups (p > 0.1). Repair of damaged hair cells was observed
      histologically. The percentage of the damaged outer hair cells (OHC) and inner
      hair cells (IHC) were determined to be as follows: GM-group: 43% and 20%, GMFF
      group: 20% and 2%, FF-group: 9% and 2% and S-group: 4% and 1%. The GMFF-group
      showed less damage to the OHC (p > 0.05) and significantly less damage to the IHC
      (p < 0.05) than the GM-group. FF did not change the antimicrobial activity of GM
      and it did not show any intrinsic antibacterial effect. FF did not affect the
      kinetics of GM during the course of the experiment.

PMID- 15476312
TI  - Diterpenoids with inhibitory activity against NFAT transcription factor from
      Acanthopanax koreanum.
AB  - Six diterpenoids and two diterpene glycosides were isolated from the
      dichloromethane and the water fractions of Acanthopanax koreanum roots,
      respectively. Of these compounds, 16alphaH, 17-isovaleryloxy-ent-kauran-19-oic
      acid containing an isovaleryloxy group at C-17 was found to exhibit the strongest
      inhibitory activity (IC(50), 6.7 microm) against NFAT transcription factor.
      However, sumogaside, 16alpha-hydroxy-ent-kauran-19-oic acid and paniculosides IV
      containing a hydroxy group at C-16 or a glycoside at C-4 carboxyl acid showed no
      activity.

PMID- 15476313
TI  - The rediscovery of ancient Chinese herbal formulas.
AB  - This review presents some recent discoveries of ancient Chinese herbal formulas
      evolved through thousands of years of clinical practice. It appears that many of
      the ancient combination formulas have sound scientific basis through modern
      pharmacological evaluation. Significant chemical changes occurred during the
      preparation (decoction) process of a prescribed herbal formula. For example, some
      toxic ingredients were significantly reduced and new active compounds generated
      due to the chemical interactions among the ingredients. Many combination formulas
      showed significantly better pharmacological results than individual herbal
      medicines participated in the formula. These findings suggest that the current
      drug screening and regulatory methodology will not be appropriate for the
      development of a botanical drug containing a group of phytochemicals, in which a
      synergistic interaction from chemical ingredients plays a fundamental role in the
      treatment of disease. If we view a diseased state in a holistic and dynamic way,
      i.e. it involves interactions among many biological systems in human body and
      these interactions change as the disease improves or worsens, the treatment of
      such disease with a single chemical entity may not be logical or technically
      feasible. Combination formulas may hold the potential to become the therapeutics
      of choice in the future due to the synergistic effect and dynamic adjustment
      achieved by the multiple ingredients that will restore the balance of an
      imbalanced or diseased human body.

PMID- 15476314
TI  - Cytotoxic effect of root extract of Tiliacora racemosa and oil of Semecarpus
      anacardium nut in human tumour cells.
AB  - Tiliacora racemosa and Semecarpus anacardium, the two plants frequently used in
      Ayurvedic medicine for the treatment of cancerous diseases, have been selected to
      examine their action in four human tumour cell lines: acute myeloblastic
      leukaemia (HL-60), chronic myelogenic leukaemia (K-562), breast adenocarcinoma
      (MCF-7) and cervical epithelial carcinoma (HeLa). In cells grown in appropriate
      media the ethanol extract of T. racemosa root, the total alkaloids isolated from
      this organ and S. anacardium nut oil prepared according to the Ayurvedic
      principle were found to have cytotoxic activity. The alkaloid fraction from T.
      racemosa had maximum cytotoxicity and was effective against all four cell lines.
      S. anacardium oil was cytotoxic only in leukaemic cells. These herbal
      preparations were not cytotoxic towards normal human lymphocytes, suggesting
      their action is specific for tumour cells. On microscopic examination the cells
      treated with these agents exhibited characteristic morphological features of
      apoptosis, such as cell shrinkage, and the formation of apoptotic bodies.
      Fluorescent staining with propidium iodide revealed distinct chromatin
      condensation and nuclear fragmentation. The apoptotic index paralleled the
      cytotoxic parameters, and fragmented DNA extracted free of genomic DNA from
      treated cells displayed a typical ladder pattern on gel electrophoresis.
      Apoptosis induced by alkaloids and phenolics, the active principles present in T.
      racemosa and S. anacardium, respectively, was found to be mediated by the
      activation of caspases.

PMID- 15476315
TI  - Antimicrobial activity of Mahonia aquifolium crude extract and its major isolated
      alkaloids.
AB  - The crude extract of Mahonia aquifolium (Pursh) Nutt. stem bark and its two main
      protoberberine alkaloids, berberine and jatrorrhizine, were tested for their in
      vitro antimicrobial activity. Twenty strains of coagulase-negative staphylococci
      and 20 strains of Propionibacterium acnes isolated from skin lesions of patients
      with a severe form of acne, and 20 strains of Candida sp. isolated from chronic
      vulvovaginal candidoses were tested for their susceptibility to crude extract and
      two isolated alkaloids. The minimum inhibitory concentrations obtained in this
      study illustrate the varying degrees of antibacterial and antifungal activity of
      the tested agents. The results indicate a rational basis for the traditional use
      of Mahonia aquifolium for localized skin and mucosal infection therapy, as well
      as for the possible development of a preparation for supportive therapy of the
      diseases mentioned above.

PMID- 15476316
TI  - [Challenge and opportunity in prevention and treatment of colorectal cancer in
      China].

PMID- 15476317
TI  - [Conditionally immortalized human colorectal crypt cell line].
AB  - OBJECTIVE: To establish human colorectal crypt cell line. METHODS: Colorectal
      crypt cells were separated from human fetal gut by dispase I digestion, AKP
      negative cells from fetal colorectal crypt were collected and cultured on
      Matrigel matrix. Subsequently the primary cultured cells were transfected with
      recombinant retrovirus containing human telomerase reverse transcriptase (hTERT)
      and simian virus 40 large T antigen (SV40 LT) in 48 h. The characterization of
      immortalized cells was identified after the transfection and cells were screened
      with antibiotics for 12 approximately 16 weeks and expanded. RESULTS: Mucin,
      cytokeratin-pan, 8, 19 were presented in immortalized cells by
      immunohistochemical staining; ectopic expressions of both hTERT and SV40 LT were
      also found in immortalized cells by Western blotting. Agarose electrophoresis
      showed that the cells expressed Musashi-1 mRNA. No evidence of carcinogenesis was
      found in nude mouse experiment and soft-agarose cloning test. CONCLUSION: The
      immortalized human colorectal crypt cells were characterized and the established
      cell line may be an ideal target for carcinogenesis study in vitro.

PMID- 15476318
TI  - [Study of an enhancer in promoter region of human colorectal cancer related ST13
      gene].
AB  - OBJECTIVE: To study the base sequence of an enhancer in up-stream 5'-flank near
      regulation region (from -595 to +74) of human colorectal cancer related gene
      ST13. METHODS: Several deletion PCR primers were designed. Amplified DNA
      fragments of ST13 gene 5'-flank near region were cloned with pGEMT-EASY vector
      and sequenced; then subcloned into several pGL2 report vectors respectively.
      Equal quantitative recombined DNA was transfected into SW620 cell lines and the
      luciferase activity was checked. RESULTS: Several amplified base sequence
      fragments (669 bp,263 bp,163 bp) in pGL2-Basic all enhanced and promoted
      luciferase gene expression strongly. The 47 bp and 101 bp fragments didn't
      promote luciferase gene expression. 101 bp fragment recombined with pGL2-Promoter
      enhanced luciferase gene expression distinctly (P<0.01), but the effect was less
      strong than the positive pGL2-Control(P<0.05). CONCLUSION: The base sequence 101
      bp (from -595 to -494) in up-stream 5'-flank near regulation region of colorectal
      cancer related gene ST13 is an enhancer regulating gene transcript.

PMID- 15476319
TI  - [Induction of HSF1 expression and sporadic colorectal cancer].
AB  - OBJECTIVE: To explore the activation of the signal transduction pathways related
      with the carcinogenesis of sporadic colon cancers. METHODS: A gene microarray
      monitoring activation of 8 signal transduction pathways (PathwayFinder GEArray)
      was used to screen the differentially expressed genes between colorectal cancer
      and normal colon tissue. The differentially expressed genes were further analyzed
      by RT-PCR, using RNA extracted from cancer tissue and matched normal colon mucosa
      of 35 patients with colorectal cancer. RESULTS: The expression of hsf1, hsf27 and
      inos was increased in colon cancer compared with normal colon mucosa using
      PathwayFinder GEArray. The RT-PCR results showed that the expression of hsf1 was
      detected in 86% of patients(30/35)and the expression of inos detected in 63%
      patients(22/35). CONCLUSION: Hsf1 induces heat shock stress signaling pathway,
      which might play a role in the carcinogenesis of sporadic colorectal cancer.

PMID- 15476320
TI  - [Hypermethylation of hMLH1 promoter in sporadic colorectal cancer].
AB  - OBJECTIVE: To identify CpG island hypermethylation of 5'region of hMLH1 promotor
      and to explore its relationship to microsatellite instability(MSI)in sporadic
      colorectal carcinoma. METHODS: Forty-one pairs of tissue specimens (normal and
      cancer) were collected from 41 patients with colorectal cancer. Hypermethylation
      of hMLH1 promoter was detected by methylation specific PCR; the relationship
      between methylation and clinicopathological features was analyzed. Combined with
      BAT25 and BAT26, the MSI status was detected using an automated fluorescent DNA
      sequencer. RESULTS: Hypermethylation of hMLH1 promoter was detected in 75.6 %
      (31/41) of samples. Mean age of unmethylation cases (49.2 y) was significantly
      younger than that of methylation cases (63.6 y) (P<0.05), but there were no
      differences between two groups in other clinicopathological features. MSI was
      detected in 43.9 % samples (18/41); hypermethylation of hMLH1 promoter was
      detected in 94.4 % (17/18) of MSI(+) samples, which was higher than that in MSI(
      ) samples (60.9 %,14/23, P<0.05). CONCLUSION: Age-related hypermethylation is
      generally found in patients with sporadic colorectal cancers, which may cause MSI
      and might be the mechanism in the development of colorectal cancer of elderly
      people.

PMID- 15476321
TI  - [Clinical features and mutation analysis of a poly-(A)8 tract in M3 cholinergic
      receptor gene in Chinese HNPCC families].
AB  - OBJECTIVE: To characterize the clinical features of Chinese HNPCC families and to
      screen the mutations of a poly-(A)8 tract in M3 cholinergic receptor gene in
      these families. METHODS: The clinical features of 15 Chinese HNPCC families were
      characterized. Genomic DNAs from 15 probands were prepared. PCR and direct DNA
      sequencing analysis were employed to examine the mutations of a poly-(A)8 tract
      in exon 8 of M3 cholinergic receptor gene. RESULTS: Total 55 cancer patients were
      found in 15 families including 41 cases of colorectal carcinoma with an average
      of 2.73 colorectal carcinomas developed per family. Thirty out of forty-one (73%)
      patients were diagnosed before age of 50 years. Proximal colon was involved in
      51% of patients, while anus and rectum were 40 %. Synchronous and metachronous
      multiple colorectal cancers developed in 5 patients (12%). Two thirds of families
      belonged to Lynch II syndrome, and total 18 extracolonic malignancies in 14
      patients were identified. Gastric carcinoma was the most common extracolonic
      types. In 15 HNPCC probands, no mutation was detected in the poly-(A)8 tract of
      exon 8 of M3 cholinergic receptor gene. CONCLUSION: M3 cholinergic receptor gene
      might have little relation with HNPCC in Chinese population. The criteria for
      Chinese HNPCC are useful and practical in clinical application.

PMID- 15476322
TI  - [Significance of CK20 mRNA expression in peripheral blood of colorectal cancer
      patients by real-time fluorescent quantitative RT-PCR].
AB  - OBJECTIVE: To detect the expression of cytokeratin 20 (CK20) mRNA in peripheral
      blood of colorectal carcinoma and to discuss its clinical value. METHODS: Real
      time fluorescent quantitative RT-PCR was used to detect the CK20 mRNA expression
      in the peripheral blood of 51 patients with colorectal carcinoma and 30 healthy
      volunteers. RESULTS: 27.45% of the patients showed CK20 mRNA expression, while it
      was 6.67% for the control group (P<0.025). With the progress of Dukes' stages,
      the expression level of CK20 mRNA increased, but there was no statistic
      significance (P<0.05). More samples in Dukes'C and D than in Dukes'A and B stages
      showed >10 copies/ml. CONCLUSION: The detection of CK20 mRNA expression in
      peripheral blood of patients with colorectal carcinoma may be helpful to identify
      early shedding tumor cells. It is also useful to monitor the progression of the
      disease and observe the effect of clinical treatment.

PMID- 15476323
TI  - [The optimal combination of serum tumor markers with bioinformatics in diagnosis
      of colorectal carcinoma].
AB  - OBJECTIVE: To identify the optimal combination of serum tumor markers with
      bioinformatics in diagnosis of colorectal cancer. METHODS: The serum levels of
      CEA, AFP, NSE, CA199, CA242, CA724, CA211 and TPA were detected in 128 patients
      with colorectal carcinoma and 113 health subjects. The serum tumor markers were
      evaluated with the area under curves. The optimal combination of serum tumor
      markers was selected and the diagnostic model with artificial neural network was
      established. RESULTS: CEA, CA199, CA242, CA211, CA724 were selected for the
      optimal combination and the artificial neural network was built. The model was
      evaluated by a 5-cross validation approach. The model had a specificity of 95%,
      sensitivity of 83% and positive predictive value of 95% in diagnosis of
      colorectal carcinoma. CONCLUSION: The combination of optimal serum tumor markers
      has a high sensitivity and specificity in diagnosis of colorectal carcinoma.

PMID- 15476324
TI  - [Alcohol drinking and colorectal cancer: a population-based prospective cohort
      study].
AB  - OBJECTIVE: To understand the incidence of colorectal cancer in population
      drinking or not and to validate the relationship between drinking and colorectal
      cancer. METHODS: The data obtained from a questionnaire used in a population
      based prospective screenings study in ten countries of Jiashan County was
      examined. A total of 64,102 men and women aged 30 y and older without history of
      cancer at baseline and a subcohort of 29,044 of them drinking past and current
      was conducted. Cox regression model was applied to estimate relative risk (RR).
      RESULTS: After 10 years follow-up,107 colon cancer and 135 rectal cancer cases
      were identified. Among drinkers and abstainers, the incidence density of
      colorectal cancer was 36.18 per 100 thousand and 37.26 per 100 thousand,
      respectively and there wasn't statistical significance(Z=0.52, P>0.05); The crude
      RR (95%CI) for drinker compared with never drinkers was 0.97(0.75 approximately
      1.25), and the multivariable-adjusted RR (95%CI) was 1.13(0.87 approximately
      1.48). The research power of this study was 96.99%. CONCLUSION: Alcohol drinking
      isn't one of the risk factors of colorectal cancer among Jiashan County
      population.

PMID- 15476325
TI  - [Quantitative detection of telomere binding factor 2 gene expression in non
      Hodgkin lymphoma with a real-time reverse transcription-polymerase chain reaction
      assay].
AB  - OBJECTIVE: To detect the expression levels of telomere binding factor 2 (TRF2)
      mRNA in tumor tissue of non-Hodgkin lymphoma (NHL) patients using quantitative
      real-time RT-PCR. METHODS: The target gene mRNA was amplified with RT-PCR, then
      was sequentially electrophoresed and purified as standards, and the standard
      curves of gene expression were established. The expression levels of TRF2 mRNA of
      lymphoid tissue from NHL and reactive lymphoadenopathy were detected with real
      time RT-PCR. RESULTS: The correlation coefficient was 0.996 between the amount of
      template cDNA and the intensity of fluorescence signal when gene expression
      standard curves were established. The correlation coefficient of template cDNA
      amount and grey density of bands derived from gel electrophoresis of real-time RT
      PCR final products was 0.779 (P<0.05). Of all NHL patients, expression levels of
      TRF2 mRNA of follicular lymphoma, mantle cell lymphoma and diffuse large B cell
      lymphoma were(22.943 +/-9.424) amol, (23.181 +/-5.983) amol and (18.339 +/-7.910)
      amol, respectively, which had no significant difference compared with reactive
      lymphoadenopathy [(21.796 +/-4.800) amol, P>0.05]. The expression level of TRF2
      mRNA of Burkitt lymphoma was (33.170 +/-12.841) amol, which was significantly
      higher than that of reactive lymphoadenopathy and other types of NHL (P<0.05).
      CONCLUSION: Alcohol drinking isn't one of the risk factors of colorectal cancer
      among Jiashan County population.

PMID- 15476326
TI  - [Relationship between drug resistance and the expression of NF-kappaB induced in
      leukemic cells].
AB  - OBJECTIVE: To explore the relationship between drug resistance of leukemic cells
      and the expression of both IkappaB-alpha and NF-kappaB associated with apoptosis
      induced by arsenic trioxide (As2O3) in K562 and K562/ADR cells. METHODS:
      Apoptosis was induced in K562 and K562/ADR cells cultured with As2O3 in different
      concentrations. Western blot was used to analyze the expression of NF-kappaB in
      nuclear and IkappaB-alpha in cytoplasm of these cells. Apoptosis and degradation
      of IkappaB-alpha protein were also observed by flow cytometry. RESULTS: After
      exposure to As2O3, the ratio of apoptosis cells in K562/ADR was significantly
      lower than that in K562 cells. K562/ADR [(6.33+/-1.51)%] and K562 cells [(13.25+/
      1.83)%] cultured with 1 micromol/L As2O3 were in apoptosis. When cultured with 4
      micromol/L As2O3, the apoptosis cells increased to (8.00+/-1.47)% and (50.56+/
      8.62)%, respectively. The level of IkappaB-alpha in K562 cytoplasm was down
      regulated from 88.07% to 49.21% after As2O3 stimulation, while NF-kappaB in
      nuclear was up-regulated, that was not found in K562/ADR cells. CONCLUSION: As2O3
      could induce apoptosis of K562 cells, associated with the degradation of IkappaB
      alpha and the activation of NF-kappaB. There are an elevated expression of NF
      kappaB and resistance to apoptosis induced by As2O3 in K562/ADR cells.

PMID- 15476327
TI  - [The expression of transforming growth factor beta-1 in rat model of chronic
      obstructive pulmonary disease and the effects of early drugs intervention].
AB  - OBJECTIVE: To evaluate the expression of transforming growth factor beta-1(TGF
      beta1) and the effects of early drugs intervention of chronic obstructive
      pulmonary disease(COPD) in rat model. METHODS: The COPD rat model (group B) was
      established by intratracheal instillation of lipopolysaccharide twice and daily
      exposure to cigarette smoking. Drug intervention groups received dongchongxiacao
      orally daily from the three days before the experiment (group C) and erythromycin
      by intraperitoneal injection since the third week (group D)and inhalation of
      budesonide since the forth week (group E). At the end of 10 weeks, all 40 rats
      including normal control (group A) were assessed for lung resistance (RL) and
      dynamic lung compliance (Cdyn). The expression of TGF-beta1 gene and protein were
      also observed by immunohistochemistry and semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR), respectively. RESULTS: The changes of
      pathology and pathophysiology in rat COPD model were similar to those of human
      COPD. There was a significant increase in the smooth muscle and collagen
      thickness in the airway wall of the group B in comparison with that of the group
      A. RL in group B was significantly higher than that in group A (P<0.01), while it
      was inhibited by early drugs intervention (P<0.01). Cdyn was decreased in group B
      as compared with that in group A, which was limited by erythromycin and
      budesonide intervention (P<0.01). The relative content for TGF-beta1 was
      significantly increased in the epithelial cells of the bronchi, endothelial cells
      of the pulmonary small vessel and alveolar macrophages of COPD group as compared
      with those of normal controls (P<0.01).The relative contents for TGF-beta1 in the
      epithelial of bronchi in group D and group E were significantly lower than that
      in group B, but not found in group C. There was no difference between group D and
      group E. There were statistical positive relationships between the RL and the
      relative content for TGF-beta1 in the bronchial epithelial cells, between the RL
      and the mRNA level of TGF-beta1 in the lung tissue (P<0.01 approximately 0.05).
      CONCLUSION: This rat COPD model could be helpful to obtain more information about
      airway remodeling. TGF-beta1 may play an important role during the process of
      airway remodeling, and could be influenced by early drugs intervention such as
      budesonide and erythromycin, which may imply their potency in the treatment of
      COPD. But there is not same phenomenon found in dongchongxiacao group.

PMID- 15476328
TI  - [Expression of R2 protein in gestational trophoblastic diseases].
AB  - OBJECTIVE: To study the expression of the small subunit ribonucleotide reductase
      (R2) in gestational trophoblastic diseases (GTD) and to assess its prognostic
      value. METHODS: The expression of R2 was detected with immunohistochemical method
      in 15 cases of normal villi, 38 cases of hydatidiform mole (HM), 42 cases of
      invasive moles (IM) and 18 cases of choriocarcinoma (CC). RESULTS: R2 expression
      in HM, IM and CC was significantly increased compared with that of normal villi
      (P=0.000). There were no significant differences in R2 protein expression among
      HM, IM and CC. Among 38 cases of HM, R2 expression in 8 cases with malignant
      transformation was significantly higher than in 30 cases of non-malignant
      transformation mole (P=0.02). Preoperative chemotherapy of gestational
      trophoblastic tumor including IM and CC did not influence the R2 expression.
      Compared with patients of stage I (WHO), the R2 protein in gestational
      trophoblastic tumor (GTT) patients of stage III or stage II was significantly
      increased (P=0.023 and P=0.038, respectively). The value of R2 in GTT patients
      with middle or high risk in WHO prognostic scoring system was higher than in the
      patients with low risk (P=0.018 and P=0.006, respectively). CONCLUSION: R2
      expression in GTD is increased, which may be associated with the hyperplasia of
      trophoblasts, malignant transformation of hydatidiform mole and drug resistance
      of trophoblastic tumor.

PMID- 15476329
TI  - [Effect of adenosine on electrophysiological changes of ventricular myocardium in
      rats with experimental diabetes].
AB  - OBJECTIVE: To investigate the electrophysiological changes of ventricular
      myocardium of rats with experimental diabetes and the effect of adenosine on its
      electrophysiology. METHODS: Diabetes was induced in male SD rats, using a single
      injection of alloxan into tail vein. Untreated animals were used as controls. The
      electrocardiograms (ECG) were recorded 6 weeks after diabetes was induced.
      Effects of adenosine on ventricular myocardium in diabetic rats and controls were
      observed by measuring the transmembrane potentials with conventional glass
      microelectrodes. RESULTS: QT interval in ECG and action potential duration (APD)
      at all levels (APD30, APD50, APD70 and APD90) were significantly prolonged in
      right ventricular papillary muscle 6 week after diabetes was induced. No
      differences were observed in the resting membrane potential (RP), action
      potential amplitude (APA) and overshoot (OS) as well as the maximum rate of
      depolarization (Vmax) between the diabetic rats and control rats. At
      concentration of 10 approximately 400 micromol/L, ADO had little influence on all
      transmembrane potential parameters of right ventricular papillary muscle in
      diabetic rats and controls. At 500 micromol/L, ADO shortened APD30, APD50, APD70
      and APD90 of control group, while having no effect on diabetic rats. CONCLUSION:
      QT interval in ECG and APD at all levels are significantly prolonged in right
      ventricular papillary muscle of experimentally induced-diabetic rats.

PMID- 15476330
TI  - [Expression of NOS III mRNA in different tissues of spontaneously hypertensive
      rats using RNA array].
AB  - OBJECTIVE: To evaluate the expression of nitric oxide synthase III (NOS III) mRNA
      in the heart, aorta, kidney and liver of spontaneously hypertensive rats (SHR).
      METHODS: Two hundred and ninety-four total RNA samples were obtained from the
      tissues of ventricle, aortic smooth muscle, kidney and liver of SHR and
      normotensive rats (Wistar-Kyoto rats, WKY). RNA array was used to determine the
      mRNA levels of NOS III of the two groups. RESULTS: Compared with WKY, the
      systolic blood pressure increased significantly in SHR at 6-week-old, 8-week-old,
      10-week-old and 12-week-old [(158.50 +/-7.69 vs 108.67 +/-5.89) mmHg, (174.33 +/
      4.46 vs 128.50 +/-4.97) mmHg, (198.00 +/-13.45 vs 142.00 +/-3.58) mmHg, (216.67
      +/-8.91 vs 141.17 +/-4.92) mmHg, P<0.01], and the ventricle/body weight ratio was
      significant higher at 10-week-old and 12-week-old [(4.08 +/-0.17 vs 3.59 +/-0.11,
      4.05 +/-0.18 vs 3.40 +/-0.19)mg/g, P<0.01]. In the heart tissue and the kidney,
      the mRNA levels of NOS III were significantly increased at 6-week-old, 8-week
      old, 10-week-old and 12-week-old (1.12 +/-0.18 vs 0.90 +/- 0.15, 1.46 +/- 0.34 vs
      1.06 +/-0.18, 1.66 +/- 0.31 vs 1.21 +/- 0.30, 1.98 +/- 0.40 vs 1.31 +/-0.38, P
      <0.05) and at 4-week-old, 6-week-old, 8-week-old, 10-week-old and 12-week-old
      (1.10 +/- 0.21 vs 0.81 +/-0.11, 1.28 +/-0.18 vs 0.95 +/-0.13,1.31 +/-0.23 vs 0.99
      +/-0.23, 1.70 +/-0.30 vs 1.08 +/-0.25, 1.83 +/-0.33 vs 1.15 +/-0.20, P<0.05 or
      P<0.01), respectively. There was no significant difference of the NOS III
      expression in the liver and no significant signals were detected in the aortic
      smooth muscle. CONCLUSION: The results provide the evidence of the increased
      expression of NOS III in different tissues in SHR and suggests the progressive
      nature of essential hypertension.

PMID- 15476331
TI  - [Follow-up study of mental developments in high-risk children].
AB  - OBJECTIVE: To study the mental developments in high risk children and the impact
      of the high risk factors on neurologic abnormalities, mental defect and long-term
      outcome. METHODS: The mental development of 122 children who had been exposed to
      high-risk factors and treated between March 1994 to May 1995 during their newborn
      periods was evaluated. Gesell development scales were performed when they were at
      6 and 12 months old. And Wechsler intelligence scales for children (Chinese
      version) were performed at 6 approximately 7 years old. RESULTS: The children
      exposed to hypoglycemia during their newborn period and preterm labor had
      significantly lower IQ, VIQ and PIQ scores (P <0.05). The other risk factors in
      order were low birth weight, severe anoxia, asphyxia at birth, erythrocythemia,
      hyperbilirubinemia. There was significant difference between the children exposed
      to one risk factor and those exposed to two or more risk factors (P <0.05). And
      there was significant correlation between developmental assessment at 6 and 12
      months and mental development at 6 approximately 7 years old (P<0.01).
      CONCLUSION: The impact of the high risk factors at birth on children's mental
      development is not negligible. And the risk of development abnormalities will
      increase if the children were exposed to multiple risk factors. The evaluation of
      development at 6 approximately 12 months is of predictive value for long-term
      outcome.

PMID- 15476332
TI  - [Simplified gonadorelin stimulation test in diagnosis of precocious puberty].
AB  - OBJECTIVE: To assess the diagnostic value of the simplified gonadorelin
      stimulation test for precocious puberty. METHODS: Two hundred and ninety-two
      girls with signs of advanced breast development received the gonadorelin
      stimulation test. According to the result of gonadorelin stimulation test, the
      girls were divided into 3 groups: 151 with central precocious puberty (CPP),119
      with premature thelarche (PT) and 22 with peripheral precocious puberty (PPP).
      RESULTS: LH or FSH levels at 15 min, 30 min, 60 min in PPP group were not
      significantly different (P>0.05). Those were significantly different in PT group
      (P<0.01). The highest levels of LH were at 30 min and the highest levels of FSH
      were at 60 min. LH or FSH levels at 15 min, 30 min, 60 min in CPP group were
      significantly different (P<0.01) with the highest levels at 30 min. The ratio of
      basal LH and FSH >0.2 had a diagnostic sensitivity of 48.3 % and specificity of
      69.7%. Taking the LH/FSH ratio >0.9 at 15 min, 30 min, 60 min as cut-off value,
      the diagnostic sensitivity was 80.1%, 68.9% and 38.4%, and the specificity was
      90.8%, 96.6% and 69.7%, respectively. CONCLUSION: The LH/FSH ratio>0.9 at 15 min
      after gonadorelin stimulation test can be used as a cut-off value to
      differentiate CPP from PT and blood sample at 60 min were not necessary.

PMID- 15476333
TI  - [Improvement of wound treatment in modified radical mastectomy of breast cancer].
AB  - OBJECTIVE: To evaluate the efficacy of Dexon continuous intracutaneous sewing
      (DCIS) and Redon negative pressure absorbing drainage (RNPAD) in modified radical
      mastectomy of breast cancer. METHODS: The clinical data of 128 patients treated
      with DCIS and RNPAD, and 123 cases treated with traditional sewing and negative
      pressure absorbing ball were analyzed retrospectively. RESULTS: There were 16
      cases (12.5%) of seroma formation,1 (0.8%) of skin flay necrosis among 128 cases
      treated by DCIS and RNPAD, and 47 cases (38%) of seroma formation, 16 (13%) of
      skin flay necrosis among 123 cases treated by traditional method. The
      statistically significant difference was found (P <0.001). The average length of
      post-operation hospital stay in DCIS and RNPAD group was 8.8 days compared with
      14.7 days in traditional treatment group. CONCLUSION: The use of DCIS and TNPAD
      could decrease the complication rate of breast cancer operation.

PMID- 15476334
TI  - [Minimally invasive technique of parotidectomy for benign parotid tumors].
AB  - OBJECTIVE: To evaluate a minimally invasive technique of parotidectomy in
      treatment of benign parotid tumors. METHODS: This retrospective review included
      49 patients with benign parotid gland tumors. The modified technique included
      incision, flap elevation, facial nerve dissection, the great auricular nerve
      preservation and postoperative disposal. RESULTS: All tumors were resected
      completely. The operation lasted 1.5 approximately 2.5 h; the average length of
      incisions was from 5.5 cm to 7.5 cm, and the average postoperative hospital stay
      was 4 days. There were no permanent facial nerve injury, no obvious scars and no
      depressed deformity observed postoperatively. During the 6 months approximately 5
      years following-up, no tumor recurrence was found. CONCLUSION: The minimally
      invasive technique of parotidectomy reduces the disadvantages of the traditional
      procedure, and improves the quality of operation.T.

PMID- 15476335
TI  - [Laparoscopic examination and treatment of abdominal cocoon with infertility: a
      report of 6 cases].
AB  - OBJECTIVE: To assess the abdominal cocoon complicated with infertility using
      laparoscope and its clinical management. METHODS: Six cases of abdominal cocoon
      treated in our hospital from January 1998 to December 2002 were retrospectively
      reviewed. RESULTS: Of the 6 patients all with primary and tubal infertility, 3
      received routine closed laparoscope operation, and other 3 failed for laparoscopy
      and were transferred to laparotomy. During the surgery it was found that the
      abdomen and pelvis were filled with multiple layer fibrous tissue which enveloped
      the bowel and reproductive organs, making exploration nearly impossible. It was
      difficult to ablate the envelope. CONCLUSION: Abdominal cocoon can be diagnosed
      in those primary and tubal infertile patients when the charge is hindered in the
      process of laparoscope. The optimal treatment of the infertility for those
      patients is in vitro fertilization-embryo transfer.

PMID- 15476336
TI  - [Methylenetetrahydrofolate reductase polymorphisms and colorectal cancer risk: a
      human genomic epidemiologic review].

PMID- 15476337
TI  - Borohydride anions as terminal ligands on a Fe/Mo/S cluster. Synthesis,
      structure, and characterization of the [(Cl4-cat)(PPr3)MoFe3S4(BH4)2]2(Bu4N)4
      double-fused cubane.
AB  - The synthesis and structure of the first Mo/Fe/S/BH(4) cluster is reported.
      Reaction of (Cl(4)-cat)(2)Mo(2)Fe(6)S(8)(PPr(3))(6) with 4 equiv of Bu(4)NBH(4)
      results in the formation of [(Cl(4)
      cat)(PPr(3))MoFe(3)S(4)(BH(4))(2)](2)(Bu(4)N)(4) (Cl(4)-cat = tetrachloro
      catecholate) which has been fully characterized. X-ray structural determination
      of this double-fused cubane reveals four BH(4)(-) ligands bound to four Fe atoms
      in a bidentate fashion. A synopsis of the solution characterization as well as
      the reactivity of this cluster is also presented.

PMID- 15476338
TI  - Dramatic effect of heteroatom backbone substituents on the ethylene
      polymerization behavior of bis(imino)pyridine iron catalysts.
AB  - Bis(imino)pyridine iron complexes bearing ether and thioether backbone
      substituents have been synthesized and evaluated for the polymerization of
      ethylene. The methoxy derivative is inactive whereas bulky phenoxides or
      thioether derivatives afford activities as high as the most active systems
      reported to date.

PMID- 15476339
TI  - Synthesis and luminescence of a charge-neutral, cyclometalated iridium(III)
      complex containing N--C--N- and C--N--C-coordinating terdentate ligands.
AB  - The first examples of iridium(III) complexes containing a terdentate, N--C--N
      coordinated 1,3-di(2-pyridyl)benzene derivative, cyclometalated at C2 of the
      benzene ring, are reported. This mode of binding becomes significant only if
      competitive cyclometalation at C4/C6 is blocked, and the ligand 1,3-di(2-pyridyl)
      4,6-dimethylbenzene (dpyxH) has been prepared to achieve this condition. The
      charge-neutral complex [Ir(dpyx)(dppy)], 2, (dppyH(2) = 2,6-diphenylpyridine) has
      been isolated, containing dpyx and dppy bound to the metal through one and two
      carbon atoms, respectively. A terpyridyl analogue, [Ir(dpyx)(ttpy)](PF(6))(2), 3,
      (ttpy = 4'-tolylterpyridine) has also been prepared and its X-ray crystal
      structure determined, confirming the N--C--N binding mode of dpyx. Complex 2
      emits strongly in degassed solution at 295 K (lambda(max) = 585 nm, phi = 0.21,
      tau = 3900 ns, in CH(3)CN). In solution, the excited state can also undergo
      photodissociation, through cleavage of one of the Ir-C(dppy) bonds.

PMID- 15476340
TI  - C-S bond formation reaction between a phenolate and disulfide-bridged dicopper(I)
      complexes.
AB  - A novel C-S bond formation reaction took place, when a lithium phenolate
      derivative was treated with a disulfide-bridged dicopper(I) complex or a
      bis(micro-thiolato)dicopper(II) complex under very mild conditions. The reaction
      has been suggested to proceed via a disulfide-bridged (micro-phenoxo)dicopper(I)
      complex as the common reaction intermediate. Copper(II) complexes of the modified
      ligands containing a thioether group (products of the C-S bond formation
      reaction) have been isolated and structurally characterized by X-ray analysis as
      model compounds of the active site of galactose oxidase. Mechanism of the C-S
      bond formation reaction is also discussed in relation to the biosynthetic
      mechanism of the organic cofactor Tyr-Cys of galactose oxidase.

PMID- 15476341
TI  - Preventing nitrite contamination in tetramethylammonium peroxynitrite solutions.
AB  - Peroxynitrite prepared from superoxide and nitric oxide in liquid ammonia does
      not contain detectable levels of nitrite. However, the dissolution of nitrite
      salts can lead to variable levels of peroxynitrite depending on the conditions
      used to disolve the salt. Low levels of nitrite result when frozen peroxynitrite
      solutions are first brought to +1 degrees C and then to room temperature. These
      undergo only 2-3% decomposition after 1 h, in contrast with the findings of a
      recent report (Lymar, S. V.; Khairutdinov, R. F.; Hurst, J. K. Inorg. Chem. 2003,
      42, 5259-5266), where high levels of nitrite ( approximately 20%) result from
      rapid thawing of these solutions to room temperature. Warming the frozen
      peroxynitrite solution directly to room temperature in 30 min leads to a nitrite
      level of 28%.

PMID- 15476342
TI  - Rational design and crystal structure determination of a 3-D metal-organic jungle
      gym-like open framework.
AB  - A new three-dimensional (3-D) jungle-gym-like open metal-organic framework has
      been synthesized from a two-dimensional (2-D) layer compound using a
      heterogeneous pillar insertion reaction. Both the starting 2-D layer and the
      resulting 3-D open compounds have been characterized using X-ray crystallography.

PMID- 15476343
TI  - Interweaving 3D network with double helical tubes filled by 1D coordination
      polymer chains.
AB  - The hydrothermal reaction of mellitic acid, 4,4'-bipydine, and
      Cu(CH(3)COO)(2).H(2)O gave rise to a novel 3D supramolecular architecture
      interpenetrated by three types of coordination polymer motifs. Two independent
      [[Cu(2)(mellitate)(4,4'-bpy)(H(2)O)(2)](2)(-)] 3D polymers incorporating helical
      substructures were interwoven into a 3D network with double-stranded helical
      tubes that host 1D linear polymers [Cu(4,4'-bpy)(H(2)O)(4)](2+)](n).

PMID- 15476344
TI  - [C5H14N2][(MoO3)3(SO4)].H2O: sulfated alpha-molybdena chains.
AB  - Recent work in the preparation of organically templated metal sulfates under
      hydrothermal conditions has been extended to include the sulfation of alpha
      molybdena through the synthesis of [C(5)H(14)N(2)][(MoO(3))(3)(SO(4))].H(2)O.
      Single crystals were grown under hydrothermal conditions from molybdenum oxide,
      water, sulfuric acid, and an enantiomerically pure (R)-2-methylpiperazine source
      and characterized using both single-crystal X-ray diffraction and infrared
      spectroscopy. One-dimensional [(MoO(3))(3)(SO(4))](n)(2n-) chains, based on a
      neutral alpha-molybdena backbone, are connected through an extensive hydrogen
      bonding network containing [C(5)H(14)N(2)](2+) cations and occluded water
      molecules. The direction of the hydrogen bonding is primarily dictated by the
      nucleophilicity of the respective oxide ligands, as determined using bond valence
      sums.

PMID- 15476345
TI  - Synthesis and magnetic properties of wheel-shaped [Mn12] and [Fe6] complexes.
AB  - The reactions of the ligands N-methyldiethanol amine and N-ethyldiethanol amine
      (abbreviated H(2)mdea and H(2)edea, respectively) with
      [Mn(12)O(12)(O(2)CCH(3))(16)(H(2)O)(4)] yield novel dodecanuclear wheel-shaped
      products. The capability of the ligands H(2)mdea and H(2)edea to support wheel
      structures in metals other than Mn is demonstrated with the crystal structure of
      a new hexanuclear ferric wheel.

PMID- 15476347
TI  - Cu(I) beta-diketiminates for alkene aziridination: reversible Cu-arene binding
      and catalytic nitrene transfer from PhI=NTs.
AB  - beta-Diketiminato Cu(I)-lutidine complexes [RMeNN]Cu(2,4-lutidine) (R = Me (4a),
      (i)Pr (4b)) were prepared in high yield from Tl[RMeNN] and [CuBr(2,4
      lutidine)(2)](2). Both 4a and 4b reversibly dissociate lutidine base in toluene
      to give [RMeNN]Cu(toluene) solvento complexes. A related base-free dicopper
      species [[Me(2)NN]Cu](2) (6) bridged via eta(2)-binding of opposing N-aryl rings
      could be isolated by the addition of Tl[Me(2)NN] to CuBr. The lutidine precursors
      serve as precatalysts for the aziridination of alkenes with PhI=NTs. Styrene,
      beta-methylstyrene, and cyclooctene gave the highest yields (59-96%) with a low
      olefin to PhI=NTs ratio (3:1) and 5 mol % catalyst loading.

PMID- 15476346
TI  - Addressing lead toxicity: complexation of lead(II) with thiopyrone and
      hydroxypyridinethione O,S mixed chelators.
AB  - The lead(II) ion is regarded as a serious environmental contaminant. A
      considerable need exists to develop selective ligands for remediation of this
      metal ion. Herein, the coordination chemistry of lead(II) is investigated with
      three O,S donor ligands: thiomaltol, 3-hydroxy-1-methyl-2(1H)-pyridinethione (3,2
      HOPTO), and 3-hydroxy-1,2-dimethyl-4(1H)-pyridinethione (3,4-HOPTO). The X-ray
      structures of [Pb(thiomaltolato)(2)] and [Pb(3,4-HOPTO)(2)] have been solved,
      revealing the expected 4-coordinate geometries. Electronic spectra have been
      obtained for the lead(II) complexes with all three ligands. Preliminary solution
      studies show that the thiomaltol ligand binds lead(II) preferentially over
      magnesium(II) and calcium(II); however, [Pb(thiomaltolato)(2)] is not stable in
      the presence of 1 equiv of EDTA. Tetradentate ligands derived from these O,S
      chelators are expected to generate higher affinity ligands for lead(II)
      sequestration.

PMID- 15476348
TI  - Thermally stable hematite hollow nanowires.
AB  - Thermally stable hematite (alpha-Fe(2)O(3)) hollow nanowires were synthesized by
      a vacuum-pyrolysis route from beta-FeOOH nanowires for the first time. The
      products can catalyze the oxidation of almost 100% carbon monoxide at 320 degrees
      C, exhibiting excellent catalytic performances despite their small BET surface
      area.

PMID- 15476349
TI  - (R/S)A2- or (R,S/S,R)p,p'-[Pd(kappa(2)-P,P-[P(OC6H3But2
      2,4)2N(Me)C(O)N(Me)PPh(2)]Cl2]: chirality created by ring tilting.
AB  - The reaction of the unsymmetric bisphosphanyl urea ligand P(OC(6)H(3)Bu(t)(2)
      2,4)(2)N(Me)C(O)N(Me)PPh(2) with [Pd(cod)Cl(2)] (cod = 1,5-cyclooctadiene)
      results in the chiral palladacycle (R,S)(A2)-[Pd(kappa(2)-P,P
      [P(OC(6)H(3)Bu(t)(2)-2,4)(2)N(Me)C(O)N(Me)PPh(2)]Cl(2)]. The chirality of the
      title compound is caused by the tilting of the central, six-membered PdP(2)N(2)C
      ring along one of the two P-N vectors and comprises two chiral planes and one
      chiral axis.

PMID- 15476350
TI  - Persistent phosphinyl radicals featuring a bulky amino substituent and the 2,6
      bis(trifluoromethyl)phenyl group.
AB  - Persistent phosphinyl radicals featuring the 2,6-bis(trifluoromethyl)phenyl group
      were prepared and characterized. Their electronic structure was theoretically
      investigated, and their low-temperature dimerization into the corresponding
      diphosphines was found to be strongly inhibited when the sterically very
      demanding (tert-butyl)(trimethylsilyl)amino substituent was used.

PMID- 15476351
TI  - Pyridyl-based pentadentate ligands: base-catalyzed hydrolysis of asym
      [Co(dmptacn)Cl]2+.
AB  - The [Co(dmptacn)Cl](2+) (dmptacn = 1,4-bis(pyridylmethyl)-1,4,7
      triazacyclononane) complex has been shown to be the asym isomer through 1D and 2D
      NMR studies, its optical resolution, and the single-crystal X-ray structure of
      its perchlorate salt. The kinetics of base-catalyzed hydrolysis establishes the
      usual [OH(-)] dependence (k(OH) = 0.040 M(-1) s(-1), 25 degrees C, I = 1.0 M,
      NaCl), but D-exchange experiments reveal that substantial if not complete
      reaction proceeds via the new pseudoaminate mechanism, i.e., via deprotonation at
      an alpha-CH(2) center rather than the NH. The significant kinetic isotope effect
      (k(H)/k(D) = 2.1) is interpreted in terms of rate-limiting deprotonation followed
      by reprotonation of the conjugate base at a rate competitive with loss of Cl(-).
      NMR and polarimetric studies establish geometric and optical retention for the
      hydrolysis reaction and exclude even the transient formation of a sym isomer
      intermediate.

PMID- 15476352
TI  - Factors affecting the solid-state structure and dimensionality of mercury
      cyanide/chloride double salts, and NMR characterization of coordination
      geometries.
AB  - In the reaction of organic monocationic chlorides or coordinatively saturated
      metal-ligand complex chlorides with linear, neutral Hg(CN)(2) building blocks,
      the Lewis-acidic Hg(CN)(2) moieties accept the chloride ligands to form mercury
      cyanide/chloride double salt anions that in several cases form infinite 1-D and 2
      D arrays. Thus, [PPN][Hg(CN)(2)Cl].H(2)O (1), [(n)Bu(4)N][Hg(CN)(2)Cl].0.5 H(2)O
      (2), and [Ni(terpy)(2)][Hg(CN)(2)Cl](2) (4) contain [Hg(CN)(2)Cl](2)(2-) anionic
      dimers ([PPN]Cl = bis(triphenylphosphoranylidene)ammonium chloride, [(n)Bu(4)N]Cl
      = tetrabutylammonium chloride, terpy = 2,2':6',6' '-terpyridine).
      [Cu(en)(2)][Hg(CN)(2)Cl](2) (5) is composed of alternating 1-D chloride-bridged
      [Hg(CN)(2)Cl](n)(n-) ladders and cationic columns of [Cu(en)(2)](2+) (en =
      ethylenediamine). When [Co(en)(3)]Cl(3) is reacted with 3 equiv of Hg(CN)(2), 1-D
      [[Hg(CN)(2)](2)Cl](n)(n-) ribbons and [Hg(CN)(2)Cl(2)](2-) moieties are formed;
      both form hydrogen bonds to [Co(en)(3)](3+) cations, yielding
      [Co(en)(3)][Hg(CN)(2)Cl(2)][[Hg(CN)(2)](2)Cl] (6). In
      [Co(NH(3))(6)](2)[Hg(CN)(2)](5)Cl(6).2H(2)O (7), [Co(NH(3))(6)](3+) cations and
      water molecules are sandwiched between chloride-bridged 2-D anionic
      [[Hg(CN)(2)](5)Cl(6)](n)(6n-) layers, which contain square cavities. The presence
      (or absence), number, and profile of hydrogen bond donor sites of the transition
      metal amine ligands were observed to strongly influence the structural motif and
      dimensionality adopted by the anionic double salt complex anions, while cation
      shape and cation charge had little effect. (199)Hg chemical shift tensors and
      (1)J((13)C,(199)Hg) values measured in selected compounds reveal that the NMR
      properties are dominated by the Hg(CN)(2) moiety, with little influence from the
      chloride bonding characteristics. delta(iso)((13)CN) values in the isolated
      dimers are remarkably sensitive to the local geometry.

PMID- 15476353
TI  - Synthesis, characterization, and structures of copper(II)-thiosulfate complexes
      incorporating tripodal tetraamine ligands.
AB  - The reaction of [Cu(L)(H(2)O)](2+) with an excess of thiosulfate in aqueous
      solution produces a blue to green color change indicative of thiosulfate
      coordination to Cu(II) [L = tren, Bz(3)tren, Me(6)tren, and Me(3)tren; tren =
      tris(2-aminoethyl)amine, Bz(3)tren = tris(2-benzylaminoethyl)amine, Me(6)tren =
      tris(2,2-dimethylaminoethyl)amine, and Me(3)tren = tris(2
      methylaminoethyl)amine]. In excess thiosulfate, only [Cu(Me(6)tren)(H(2)O)](2+)
      promotes the oxidation of thiosulfate to polythionates. Products suitable for
      single-crystal X-ray diffraction analyses were obtained for three thiosulfate
      complexes, namely, [Cu(tren)(S(2)O(3))].H(2)O, [Cu(Bz(3)tren)(S(2)O(3))].MeOH,
      and (H(3)Me(3)tren)[Cu(Me(3)tren)(S(2)O(3))](2)(ClO(4))(3). Isolation of
      [Cu(Me(6)tren)(S(2)O(3))] was prevented by its reactivity. In each complex, the
      copper(II) center is found in a trigonal bipyramidal (TBP) geometry consisting of
      four amine nitrogen atoms, with the bridgehead nitrogen in an axial position and
      an S-bound thiosulfate in the other axial site. Each structure exhibits H bonding
      (involving the amine ligand, thiosulfate, and solvent molecule, if present),
      forming either 2D sheets or 1D chains. The structure of
      [Cu(Me(3)tren)(MeCN)](ClO(4))(2) was also determined for comparison since no
      structures of mononuclear Cu(II)-Me(3)tren complexes have been reported. The
      thiosulfate binding constant was determined spectrophotometrically for each
      Cu(II)-amine complex. Three complexes yielded the highest values reported to date
      [K(f) = (1.82 +/- 0.09) x 10(3) M(-1) for tren, (4.30 +/- 0.21) x 10(4) M(-1) for
      Bz(3)tren, and (2.13 +/- 0.05) x 10(3) M(-1) for Me(3)tren], while for Me(6)tren,
      the binding constant was much smaller (40 +/- 10 M(-1)).

PMID- 15476354
TI  - Chiral molecular squares based on angular bipyridines: self-assembly,
      characterization, and photophysical properties.
AB  - Chiral molecular squares 1-12 based on [M(dppe)](2+) metallocorners (M = Pd or
      Pt, and dppe = bis(diphenylphosphino)ethane) and new angular bipyridine bridging
      ligands derived from the 1,1'-binaphthyl framework were readily assembled and
      characterized by a variety of techniques including infrared, UV-vis, circular
      dichroism (CD), and NMR spectroscopy, and ESI mass spectrometry. All these chiral
      metallocycles are highly luminescent in solution at room temperature with quantum
      efficiency of 0.06-0.63. Interestingly, when equal molar enantiopure molecular
      squares of opposite handedness were mixed in solution, a new meso dimeric
      metallocycle with C(2) symmetry formed. This result indicates the lability of the
      M-pyridyl bonds in these metallocycles, which may hinder their applications in
      many enantioselective processes.

PMID- 15476355
TI  - Copper(II) complexes of N-octylated bis(benzimidazole) diamide ligands and their
      peroxide-dependent oxidation of aryl alcohols.
AB  - New N-octylated benzimidazole-based diamide ligands N,N'-bis(N
      octylbenzimidazolyl-2-ethyl)hexanediamide (O-ABHA), possessing a chiral center,
      and N,N'-bis(N-octylbenzimidazolyl-2-methyl)hexanediamide (O-GBHA) have been
      synthesized and utilized to prepare Cu(II) complexes of general composition
      [Cu(L)X]X, where L = O-ABHA or O-GBHA and X = Cl(-) or NO(3)(-) . The X-ray
      structure of one of the complexes, [Cu(O-GBHA)NO(3)]NO(3), has been obtained. The
      Cu(II) ion is found to possess a distorted octahedral geometry with a highly
      unsymmetrical bidentate nitrate group. The N(2)O(2) equatorial plane comprises an
      amide carbonyl O, a nitrate O, and the two benzimidazole imine N atoms while
      another amide carbonyl O and nitrate O take up the axial positions. The complexes
      carry out the oxidation of aromatic alcohols to aldehydes in the presence of
      cumenyl hydroperoxide at 40-45 degrees C and act as catalyst with turnovers
      varying between 13- and 27-fold. The percentage yields of the respective products
      have been obtained which vary from 32% to 65% with respect to the catalyst
      turnover.

PMID- 15476356
TI  - An infinite zigzag chain of alternating Cl-Pd-Pd-Cl and Mo-Mo units.
AB  - Treatment of Pd(2)Cl(2)(CNC(6)H(3)Me(2)-2,6)(4) (1) with Mo(2)(O(2)CCF(3))(4) (2)
      in dichloromethane afforded an infinite zigzag chain [[Pd(2)Cl(2)(CNC(6)H(3)Me(2)
      2,6)(4)][Mo(2)(O(2)CCF(3))(4)]](n) (3), where two metal-metal bonded dinuclear Pd
      Pd and Mo-Mo units were bridged by chloro atoms. The Mo-Mo distance (2.1312(3) A)
      of 3 is significantly elongated compared to that of 2 (2.090(4) A) and lies in
      the range of that of the quadruple Mo-Mo bonded complexes. Such elongation might
      be attributed to the axial donation of the chloro atoms of the Pd-Pd unit to the
      Mo-Mo moiety.

PMID- 15476357
TI  - Copper(III) and vanadium(IV)-oxo corrolazines.
AB  - As part of our efforts to develop the transition metal chemistry of corrolazines,
      which are ring-contracted porphyrinoid species most closely related to corroles,
      the vanadium and copper complexes (TBP)(8)Cz(H)V(IV)O (1) and (TBP)(8)CzCu(III)
      (2) of the ligand octakis(para-tert-butylphenyl)corrolazine [(TBP)(8)Cz] have
      been synthesized. The coordination behavior, preferred oxidation states, and
      general redox properties of metallocorrolazines are of particular interest. The
      corrolazine ligand in 1 was shown to contain a labile proton by acid/base
      titration and IR spectroscopy, serving as a -2 ligand rather than as the usual -3
      donor. The oxidation state of the vanadium center in 1 was shown to be +4, in
      agreement with the overall neutral charge for this complex. The EPR spectrum of 1
      reveals a rich signal consistent with a V(IV)(O) (d(1), S = 1/2) porphyrinoid
      species (g(xx) = 1.989, g(yy) = 1.972, g(zz) = 1.962). The electrochemical
      analysis of 1 shows behavior closer to that of a porphyrazine than a corrolazine,
      with a positively shifted, irreversible reduction at -0.65 V (vs Ag/AgCl).
      Resonance Raman and IR data for 1 confirm the presence of a triply bonded
      terminal oxo ligand with nu(V(16)O) = 975 cm(-1) and nu(V(18)O) = 939 cm(-1). The
      copper complex 2 exhibits a diamagnetic (1)H NMR spectrum, indicative of a bona
      fide square planar copper(III) (d(8), low-spin) complex. Previously reported
      copper corroles have been characterized as copper(III) complexes which exhibit a
      paramagnetic NMR spectrum at higher temperatures, indicative of a thermally
      accessible triplet excited state ([(corrole(*+))Cu(II)]). The NMR spectrum for 2
      shows no paramagnetic behavior in the range 300-400 K, indicating that compound 2
      does not have a thermally accessible triplet excited state. These data show that
      the corrolazine system is better able to stabilize the high oxidation state
      copper center than the corresponding corroles. Electrochemical studies of 2
      reveal two reversible processes at +0.93 and -0.05 V, and bulk reduction of 2
      with NaBH(4) generates the copper(II) species [(TBP)(8)CzCu(II)](-) (2a), which
      exhibits an EPR signal typical of a copper(II) porphyrinoid species.

PMID- 15476358
TI  - Impact of variations in design of flexible bitopic bis(pyrazolyl)methane ligands
      and counterions on the structures of silver(I) complexes: dominance of cyclic
      dimeric architecture.
AB  - The new ligands 1,1,4,4-tetra(1-pyrazolyl)butane [CH(pz)(2)(CH(2))(2)CH(pz)(2),
      L2] and 1,1,5,5-tetra(1-pyrazolyl)pentane [CH(pz)(2)(CH(2))(3)CH(pz)(2), L3] have
      been prepared to determine the structural changes in silver(I) complexes, if any,
      that accompany the lengthening of the spacer group between two linked
      bis(pyrazolyl)methane units. Silver(I) complexes of both ligands with BF(4)(-)
      and SO(3)CF(3)(-) as the counterion have the formula [Ag(2)(micro
      L)(2)](counterion)(2). These complexes have a cyclic dimeric structure in the
      solid state previously observed with the shorter linked ligand
      CH(pz)(2)CH(2)CH(pz)(2). Similar chemistry starting with AgNO(3) for L2 yields a
      complex of the empirical formula [Ag(2)[micro
      CH(pz)(2)(CH(2))(2)CH(pz)(2)](3)](NO(3))(2) that retains the cyclic dimeric
      structure, but bonding of an additional ligand creates a coordination polymer of
      the cyclic dimers. In contrast, coordination of the nitrate counterion to silver
      in the complex of L3 leads to the formation of the coordination polymer of the
      empirical formula [Ag(micro-CH(pz)(2)(CH(2))(3)CH(pz)(2))]NO(3). All six new
      complexes have extended supramolecular structures based on noncovalent
      interactions supported by the counterions and the functional groups designed into
      the ligands.

PMID- 15476359
TI  - New types of heterospin complexes from trans-oxamido-bridged copper(II) binuclear
      units and nitronyl nitroxide radicals: crystal structure and magnetic
      characterization.
AB  - Three new heterospin complexes derived from trans-oxamido-bridged copper(II)
      binuclear units [Cu(2)(oxen), oxen = N,N-bis(2-aminoethyl)oxamide] and pyridine
      substituted nitronyl nitroxides (o-, m-, and p-PYNN) were synthesized and
      characterized structurally and magnetically. Complexes 1 and 2 are four-spin
      complexes. Interestingly, it is found that in complex 3, the Cu(II) ions and m
      PYNN units are arranged to form 1D double-stranded helical chains, which to the
      best of our knowledge is the first example of a metal nitronyl nitroxide complex
      with such a 1D helical structure. The temperature dependencies of the magnetic
      susceptibilities of 1 and 2 were fitted to the four-spin model with the
      Hamiltonian H = -2Js(Cu1)s(Cu2) - 2j(s(Cu1)s(rad1) - s(Cu2)s(rad2)), leading to J
      = -150.5 cm(-)(1) and j = 47.2 cm(-)(1) for complex 1 and J = -191.7 cm(-)(1) and
      j = -18.9 cm(-)(1) for complex 2. The temperature dependence of the magnetic
      susceptibility of complex 3 was approximately simulated with a simple model
      composed of a dimer of Cu(II) ions and two m-PYNN molecules. The best fitting
      leads to the values of J = -183.0 cm(-)(1) and zJ' = -0.55 cm(-)(1) for the
      magnetic exchange of two Cu(II) ions through the oxamide bridge and that between
      the dimer of Cu(II) ions and two m-PYNN molecules, respectively. The
      antiferromagnetic exchange of oxamido-bridged Cu(II) ions in complexes 1-3 is
      strong. The strength of such antiferromagnetic interactions is also similar for
      the three complexes.

PMID- 15476360
TI  - Structure-energy relations in methylcobalamin with and without bound axial base.
AB  - The properties of the Co-C bond in methylcobalamin (MeCbl) are analyzed by means
      of first-principles molecular dynamics. The optimized structure is in very good
      agreement with experiments, reproducing the bent-up deformation of the corrin
      ring as well as the metal-ligand bond distances. The analysis of the binding
      energies, bond orders, and vibrational stretching frequencies shows that the
      axial base slightly weakens the Co-C bond (by 4%), while the alkyl ligand
      substantially reinforces the Co-axial base bond (by 90%). These findings support
      several experiments and provide insight into the conversion between the base-on
      and base-off forms of the MeCbl cofactor.

PMID- 15476361
TI  - Magnetic ordering in iron tricyanomethanide.
AB  - Magnetic susceptibility, heat capacity, and neutron diffraction studies of
      Fe[C(CN)(3)](2) reveal the existence of two magnetic phase transitions at T(N,I)
      = 2.45 K and T(N,II) = 1.85 K. Between 1.85 and 2.45 K, the magnetic ordering is
      incommensurate with a temperature-dependent propagation vector (k(I,x) 0 0),
      k(I,x) = 0.525-0.540. In zero magnetic field, below 1.85 K the ordered structure
      is described by the propagation vector k(II) = ((1/2) 0 (1/2)), i.e., a doubling
      of the unit cell along the a and c directions of the orthorhombic lattice. The
      ordered moments of 3.4(1) and 3.2(1) micro(B), respectively, are aligned
      approximately parallel to the principal axis of the elongated Fe coordination
      octahedron. At T < T(N,II), application of an external magnetic field of about 18
      kOe destroys the commensurate phase and the incommensurate phase is established.
      The latter phase is stable in fields up to about 40 kOe. The magnetic ordering of
      Fe[C(CN)(3)](2) is discussed in terms of the 2D triangular topology of the
      lattice, producing partial frustration, and in comparison with the behavior of
      other compounds of the series M[C(CN)(3)](2), where M is a 3d transition metal.

PMID- 15476362
TI  - Uranium (III) scorpionates: synthesis and structure of [(TpMe2)2U[N(C6H5)2]] and
      [(TpMe2)2U[N(SiMe3)2]].
AB  - Reaction of [(Tp(Me)2)(2)UI] with KNR(2) (R = C(6)H(5), SiMe(3)) in
      tetrahydrofuran (THF) afforded the monomeric trivalent actinide amide complexes
      [(Tp(Me)2)(2)U[N(C(6)H(5))(2)]], 1, and [(Tp(Me)2)(2)U[N(SiMe(3))(2)]], 2. The
      complexes have been fully characterized by spectroscopic methods and their
      structures were confirmed by X-ray crystallographic studies. In the solid state 1
      and 2 exhibit distorted pentagonal bipyramidal geometries. The U-NR(2) bond
      lengths in both complexes are the same but in complex 2 the greater steric
      demands of the N(SiMe(3))(2) ligand led to elongated U-N(pz) bonds, especially
      those opposite the amido ligand.

PMID- 15476363
TI  - Chiral recognition and resolution of the enantiomers of supramolecular triangular
      hosts: synthesis, circular dichroism, NMR, and X-ray molecular structure of [Li
      subset(R,R,R)-[CpRh(5-chloro-2,3-dioxopyridine)]3][Delta-Trisphat].
AB  - The racemic triangular supramolecular host [CpRh(5-chloro-2,3-dioxopyridine)](3)
      (1) was prepared in high yield. Treatment with LiCl followed by addition of
      silver salt AgOTf gave the triflate salt species [Li subset[CpRh(5-chloro-2,3
      dioxopyridine)](3)][OTf] (2). Subsequent anion metathesis using the optically
      pure chiral shift reagent [Cinchonidinium][Delta-Trisphat] produced a pair of
      diastereomers [Li subset(R,R,R)-[CpRh(5-chloro-2,3-dioxopyridine)](3)][Delta
      Trisphat] (3a) and [Li subset(S,S,S)-[CpRh(5-chloro-2,3-dioxopyridine)](3)][Delta
      Trisphat] (3b). The resolution of these diastereomers was achieved by fractional
      crystallization, and their stereochemistry relationship was established by
      circular dichroism studies. The X-ray molecular structure of 3a is reported and
      shows as an outstanding feature a chiral recognition between the Delta-Trisphat
      anion and a single enantiomer cation [Li subset(R,R,R)-[CpRh(5-chloro-2,3
      dioxopyridine)](3)](+) manifested through a pi-pi interaction. (1)H NMR and
      circular dichroism studies in solution support the solid-state behavior.

PMID- 15476364
TI  - Synthesis and characterization of a discotic uranium-containing liquid crystal.
AB  - The synthesis of several UO(2)-alaskaphyrin derivatives functionalized with
      aliphatic chains is described. These compounds are found to be liquid-crystalline
      and form columnar mesophases, as judged from polarizing optical microscopy
      studies, and represent the first uranium-containing discotic mesogens.

PMID- 15476365
TI  - Conformational flexibility of nickel(II) benziporphyrins.
AB  - (1)H NMR spectra of three paramagnetic Ni(II) complexes of benziporphyrins have
      been investigated in a broad temperature range. For the m- and p-benziporphyrin
      complexes, the line widths of certain signals exhibit an unusual temperature
      dependence characteristic of a dynamic process. This behavior is interpreted in
      terms of an equilibrium in which one of the forms is present at a very small
      concentration and cannot be observed directly. For the benziporphodimethene
      complex, the two exchanging forms are present at comparable concentrations and
      can yield separate signals in the slow exchange limit. To account for the
      observed exchange process, a mechanism is proposed involving the motion of the
      phenylene moiety. This hypothesis is further explored with DFT modeling, which
      indicates that the postulated conformers are thermally accessible.

PMID- 15476366
TI  - Silver(I) arylsulfonates: a systematic study of "softer" hybrid inorganic-organic
      solids.
AB  - The present study represents the first systematic examination of the effects on
      the layered structure of simple silver aryl-monosulfonates as the breadth of the
      pendant aryl group is increased beyond that where a simple "phosphonate-like"
      motif is sustainable. Five new silver arenesulfonates are reported. On the basis
      of comparison with Ag benzenesulfonate, a threshold of approximately 6.4 A is
      proposed and confirmed as the critical breadth of an aryl group for a simple
      layered motif to be observed in silver sulfonates. Ag 1,1'-biphenyl-4-sulfonate
      (1) and Ag 2-naphthalenesulfonate (2) are below this threshold and so form simple
      layered networks, termed type 1 solids. When the pendant group is broadened to a
      1-naphthyl group, the layer incorporates coordinated water to maintain a layered
      structure giving Ag 1-naphthalenesulfonate hemihydrate (3a). This more diffuse
      structure is termed a type 2 solid. For anhydrous Ag 1-naphthalenesulfonate (3)
      and Ag 1-pyrenesulfonate (4), the additional breadth is compensated for by the
      formation of Ag-pi interactions and the formation of type 3 solids. Interactions
      between the pendant groups are observed to play a significant role in the packing
      of the solid. All frameworks are characterized by single crystal and powder X-ray
      diffraction, IR, DSC-TGA, and elemental analysis. The significance of this
      adaptable framework is discussed along with implications for design of stacked
      arene arrays.

PMID- 15476367
TI  - Nature of metal binding sites in Cu(II) complexes with histidine and related N
      coordinating ligands, as studied by EXAFS.
AB  - Knowledge of the complexes formed by N-coordinating ligands and Cu(II) ions is of
      relevance in understanding the interactions of this ion with biomolecules. Within
      this framework, we investigated Cu(II) complexation with mono- and polydentate
      ligands, such as ammonia, ethylenediamine (en), and phthalocyanine (Pc). The
      obtained Cu-N coordination distances were 2.02 A for [Cu(NH(3))(4)](2+), 2.01 A
      for [Cu(en)(2)](2+), and 1.95 A for CuPc. The shorter bond distance found for
      CuPc is attributed to the macrocyclic effect. In addition to the structure of the
      first shell, information on higher coordination shells of the chelate ligands
      could be extracted by EXAFS, thus allowing discrimination among the different
      coordination modes. This was possible due to the geometry of the complexes, where
      the absorbing Cu atoms are coplanar with the four N atoms forming the first
      coordination shell of the complex. For this reason multiple scattering
      contributions become relevant, thus allowing determination of higher shells. This
      knowledge has been used to gain information about the structure of the 1:2
      complexes formed by Cu(II) ions with the amino acids histidine and glycine, both
      showing a high affinity for Cu(II) ions. The in-solution structure of these
      complexes, particularly that with histidine, is not clear yet, probably due to
      the various possible coordination modes. In this case the square-planar
      arrangements glycine-histamine and histamine-histamine as well as tetrahedral
      coordination modes have been considered. The obtained first-shell Cu-N
      coordination distance for this complex is 1.99 A. The results of the higher
      shells EXAFS analysis point to the fact that the predominant coordination mode is
      the so-called histamine-histamine one in which both histidine molecules
      coordinate Cu(II) cations through N atoms from the amino group and from the
      imidazole ring.

PMID- 15476368
TI  - A comparative XAS and X-ray diffraction study of new binuclear Mn(III) complexes
      with catalase activity. indirect effect of the counteranion on magnetic
      properties.
AB  - Four new binuclear Mn(III) complexes with carboxylate bridges have been
      synthesized: [[Mn(nn)(H(2)O)](2)(mu-ClCH(2)COO)(2)(mu-O)](ClO(4))(2) with nn =
      bpy (1) or phen (2) and [[Mn(bpy)(H(2)O)](2)(mu-RCOO)(2)(mu-O)](NO(3))(2) with
      RCOO = ClCH(2)COO (3) or CH(3)COO (4). The characterization by X-ray diffraction
      (1 and 3) and X-ray absorption spectroscopy (XAS) (1-4) displays the relevance of
      this spectroscopy to the elucidation of the structural environment of the
      manganese ions in this kind of compound. Magnetic susceptibility data show an
      antiferromagnetic coupling for all the compounds: J = -2.89 cm(-1) (for 1), -8.16
      cm(-1) (for 2), -0.68 cm(-1) (for 3), and -2.34 cm(-1) (for 4). Compounds 1 and 3
      have the same cation complex [[Mn(bpy)(H(2)O)](2)(mu-ClCH(2)COO)(2)(mu-O)](2+),
      but, while 1 shows an antiferromagnetic coupling, for 3 the magnetic interaction
      between Mn(III) ions is very weak. The four compounds show catalase activity, and
      when the reaction stopped, Mn(II) compounds with different nuclearity could be
      obtained: binuclear [[Mn(phen)(2)](mu-ClCH(2)COO)(2)](ClO(4))(2), trinuclear
      [Mn(3)(bpy)(2)(mu-ClCH(2)COO)(6)], or mononuclear complexes without carboxylate.
      Two Mn(II) compounds without carboxylate have been characterized by X-ray
      diffraction: [Mn(NO(3))(2)(bpy)(2)][Mn(NO(3))(bpy)(2)(H(2)O)]NO(3) (5) and
      [Mn(bpy)(3)](ClO(4))(2).0.5 C(6)H(4)-1,2-(COOEt)(2).0.5H(2)O (8).

PMID- 15476369
TI  - New tetranuclear Cu(II) complexes: synthesis, structure, and magnetic properties.
AB  - The synthesis, structure, and magnetic properties of two new tetranuclear Cu(II)
      complexes containing N,N,N',N'-tetraethylpyridine-2,6-dithiocarboxamide (S-dept)
      of formula [Cu(2)Cl(2)(mu-S-dept)(2)][Cu(2)Cl(4)(mu-Cl)(2)] (1) and [Cu(2)(mu
      Cl)(2)(S-dept)(2)][CuCl(3)(EtOH)](2) (2) are reported. Their X-ray crystal
      structures reveal that the complexes are composed of anionic and cationic dimers,
      that in both cases contain the metal centers which interact via Coulombic and/or
      hydrogen bonding interactions. In both cases, the Cu centers in the anionic
      moieties adopt a slightly distorted tetrahedral geometry whereas for the cationic
      moieties they adopt a square-pyramidal type of geometry. Magnetic susceptibility
      data show that compounds 1 and 2 present an overall antiferromagnetic behavior
      arising from the contribution of both anionic and cationic moieties. For 1, the
      best fit obtained gave J(1) = -2.62 +/- 0.19 cm(-1), J(2) = -19.54 +/- 0.47 cm(
      1), and g(2) = 2.164 +/- 0.004 cm(-1) (R = 8.28 x 10(-5)) whereas for 2 it gave
      J(1) = 4.48 +/- 2.73 cm(-1), g(1) = 2.20 +/- 0.03, J(2) = -11.26 +/- 2.01 cm(-1),
      and g(2) = 2.10 +/- 0.03 (R = 1.15 x 10(-4)). The nature of the superexchange
      pathways in 1 and 2 is discussed on the basis of structural, magnetic, and
      molecular orbital considerations. Theoretical calculations are performed at the
      extended Huckel level in order to obtain their molecular orbitals and energies
      using their crystallographic data.

PMID- 15476370
TI  - A comparison of structure and stability between the group 11 halide tetramers
      M4X4 (M = Cu, Ag, or Au; X = F, Cl, Br, or I) and the group 11 chloride and
      bromide phosphanes (XMPH3)4.
AB  - The tetramers of the group 11 (I) halides, M(4)X(4) (M = Cu, Ag, or Au; X = F,
      Cl, Br, or I), and corresponding group 11 (I) phosphanes, chloride and bromide
      (XMPH(3))(4) (X = Cl or Br), are investigated by the density functional theory.
      All coinage metal(I) halide tetramers adopt squarelike ring structures with an
      out-of-plane distorted (butterfly) D(2d) symmetry. These structures are much
      lower in energy than the more compact cubelike T(d) arrangements, which maximize
      dipole-dipole interactions and more closely resemble the solid-state structures
      of the copper and silver halides. Phosphine coordination completely changes the
      structures of these M(4)X(4) clusters. The copper(I) and silver(I) phosphane
      chloride and bromide tetramers adopt a heterocubane structure, slightly preferred
      over a step (ladder-type)-cluster structure well-known in the coordination
      chemistry of such compounds. In stark contrast, gold(I) phosphane chloride and
      bromide tetramers prefer assemblies of linear XAuPH(3) units with direct gold
      gold contacts, resulting in a square planar, centered trigonal planar, or
      tetrahedral gold core.

PMID- 15476371
TI  - Well-defined calcium initiators for lactide polymerization.
AB  - A series of monomeric amide or aryloxide complexes of the form LCaX, where L =
      CH[CMeNC(6)H(3)-2,6-](2), CH[CMeNC(6)H(4)-2-OMe](2), a bulky tris-pyrazolyl
      borate, Tp(iPr) or Tp(tBu) or 9-BBN-pz(2) and X = N(SiMe(3))(2) or OC(6)H(3)-2,6
      , has been prepared and characterized and investigated in the ring-opening
      polymerizations of lactide. The compounds (Tp(tBu))CaX in THF are shown to be
      highly active and stereoselective. The propylene oxide complex
      (Tp(tBu))Ca(OC(6)H(3)-2,6-).(PO) has been isolated and structurally characterized
      (single-crystal X-ray) and shown to be inert to the polymerization of PO.

PMID- 15476372
TI  - Decomposition kinetics of Ni(III)-peptide complexes with histidine and histamine
      as the third residue.
AB  - The decomposition kinetics of the Ni(III) complexes of Gly(2)HisGly and Gly(2)Ha
      are studied from p[H(+)] 3.5 to 10, where His is l-histidine and Ha is histamine.
      In these redox reactions, at least two Ni(III) complexes are reduced to Ni(II)
      while oxidizing a single peptide ligand. The rate of Ni(III) loss is first order
      at low pH, mixed order from pH 7.0 to 8.5, and second order at higher pH. The
      transition from first- to second-order kinetics is attributed to the formation of
      an oxo-bridged Ni(III)-peptide dimer. The rates of decay of the Ni(III) complexes
      are general-base assisted with Bronsted beta values of 0.62 and 0.59 for
      Ni(III)Gly(2)HisGly and Ni(III)Gly(2)Ha, respectively. The coordination of
      Gly(2)HisGly and Gly(2)Ha to Ni(II) are examined by UV-vis and CD spectroscopy.
      The square planar Ni(II)(H(-2)Gly(2)HisGly)(-) and Ni(II)(H(-2)Gly(2)Ha)
      complexes lose an additional proton from an imidazole nitrogen at high pH with
      pK(a) values of 11.74 and 11.54, respectively. The corresponding Ni(III)
      complexes have axially coordinated water molecules with pK(a) values of 9.37 and
      9.44. At higher pH an additional proton is lost from the imidazole nitrogen with
      a pK(a) value of 10.50 to give Ni(III)(H(-3)Gly(2)Ha)(H(2)O)(OH)(2-).

PMID- 15476373
TI  - Density functional investigation of metal-metal interactions in mixed-valence
      d2d3 (Cr, Mo, W) and d3d4 (Mn, Tc, Re) face-shared [M2Cl9]2- systems.
AB  - The molecular and electronic structures of mixed-valence face-shared (Cr, Mo, W)
      d(2)d(3) and (Mn, Tc, Re) d(3)d(4) [M(2)Cl(9)](2-) dimers have been calculated by
      density functional methods in order to investigate metal-metal bonding in this
      series. The electronic structures of these systems have been analyzed using
      potential energy curves for the broken-symmetry and other spin states arising
      from the d(2)d(3) and d(3)d(4) coupling modes. In (d(2)d(3)) [Mo(2)Cl(9)](2-) and
      [W(2)Cl(9)](2-), the global minimum has been found to be a spin-doublet state
      characterized by delocalization of the metal-based electrons in a multiple metal
      metal bond (with a formal bond order of 2.5). In contrast, weak coupling between
      the metal centers and electron localization are favored in (d(2)d(3))
      [Cr(2)Cl(9)](2-), the global minimum for this species being a ferromagnetic S =
      5/2 state with a relatively long Cr-Cr separation. The (d(3)d(4)) [Re(2)Cl(9)](2
      ) system also exhibits a global minimum corresponding to a metal-metal bonded
      spin-doublet state with a formal bond order of 2.5, reflecting the electron-hole
      equivalence between d(2)d(3) and d(3)d(4) configurations. Double minima behavior
      is predicted for (d(3)d(4)) [Tc(2)Cl(9)](2-) and [Mn(2)Cl(9)](2-) due to two
      energetically close low-lying states (these being S = 3/2 and S = 5/2 states for
      the former, and S = 5/2 and S = 7/2 states for the latter). A comparison of
      computational results for the d(2)d(2), d(2)d(3), and d(3)d(3) [W(2)Cl(9)](z-)
      series and the d(3)d(3), d(3)d(4), and d(4)d(4) [Re(2)Cl(9)](z-) series indicates
      that the observed trends in metal-metal distances can only be rationalized if
      changes in both the strength of sigma bonding and metal-metal bond order are
      taken into consideration. These two factors act conjointly in the W series but in
      opposition to one another in the Re series. In the case of the [Cr(2)Cl(9)](z-)
      and [Mn(2)Cl(9)](z-) dimers, the metal-metal bond lengths are significantly
      shorter for mixed-valence (d(2)d(3) or d(3)d(4)) than d(3)d(3) systems. This
      result is consistent with the fact that some degree of metal-metal bonding exists
      in the former (due to partial delocalization of a single sigma electron) but not
      in the latter (where all metal-based electrons are completely localized).

PMID- 15476374
TI  - Europium(III) interaction with a polyaza-aromatic extractant studied by time
      resolved laser-induced luminescence: a thermodynamical approach.
AB  - The 2,6-bis(5,6-dialkyl-1,2,4-triazin-3-yl)pyridines (DATPs) belong to a new
      family of extracting agents recently developed in the framework of nuclear fuel
      reprocessing. These molecules exhibit exceptional properties to separate
      actinides(III) from lanthanides(III) in nitric acid solutions. In a previous
      work, the use of electrospray ionization mass spectrometry (ESI-MS) provided data
      such as stoichiometries and conditional stability constants of various DATP
      complexes with europium and evidenced the unusual capability of DiPTP [bis(di-iso
      propyltriazinyl)pyridine] ligand to form 1:3 complexes in nitric acid solution.
      This latter result has then been further investigated by considering DiPTP
      complexation features with the complete lanthanide family. Moreover, a
      complementary study of equilibria in solution with a non intrusive technique such
      as time-resolved laser-induced luminescence (TRLIL) seemed quite promising to
      determine thermochemical data such as enthalpy and entropy variations associated
      with the complexation reaction between Eu(III) and DiPTP. Furthermore, this TRLIL
      study may also allow ensuring that the observations made on mass spectra actually
      reflected the equilibrium in solution and not an intermediate state between
      liquid phase and gaseous phase. The investigation of europium(III) complexation
      with DiPTP by TRLIL described in this paper first led to highlight the exclusive
      formation of a 1:3 complex between europium(III) and the DiPTP ligand,
      specificity already pointed out by ESI-MS. Two different calculation methods,
      using either luminescence spectra and luminescence decay curves, have then been
      used to measure the conditional stability constant of the [Eu(DiPTP)(3)](3+)
      complex. Both methods gave similar results (log beta3(app)= 14.3 +/- 0.6 at pH
      2.8) in good agreement with the one previously reported in ESI-MS studies (log
      beta3(app)= 14.0 +/- 0.6 at pH 2.8). Moreover, while considering the influence of
      temperature on the value of the stability constant, it was possible to estimate
      the enthalpy (DeltaH(beta3) = -29 +/- 3 kJ mol(-1) at pH 2.8) and entropy
      variations (DeltaS(beta3) = 173 +/- 10 J K(-1) mol(-1) at pH 2.8) associated with
      the [Eu(DiPTP)(3)](3+) complex formation.

PMID- 15476375
TI  - Zn2+-catalyzed methanolysis of phosphate triesters: a process for catalytic
      degradation of the organophosphorus pesticides paraoxon and fenitrothion.
AB  - The methanolyses of two neutral phosphorus triesters, paraoxon (1) and
      fenitrothion (3), were investigated as a function of added Zn(OTf)(2) or
      Zn(ClO(4))(2) in methanol at 25 degrees C either alone or in the presence of
      equimolar concentrations of the ligands phenanthroline (4), 2,9
      dimethylphenanthroline (5), and 1,5,9-triazacyclododecane (6). The catalysis
      requires the presence of methoxide, and when studied as a function of added
      NaOCH(3), the rate constants (k(obs)) for methanolysis of Zn(2+) alone or in the
      presence of equimolar 4 or 5 maximize at different [(-)OCH(3)]/[Zn(2+)](total)
      ratios of 0.3, 0.5, and 1.0, respectively. Plots of k(obs) vs [Zn(2+)](total)
      either alone or in the presence of equimolar ligands 4 and 5 at the [(
      )OCH(3)]/[Zn(2+)](total) ratios corresponding to the rate maxima are curved and
      show a nonlinear dependence on [Zn(2+)](total). In the cases of 4 and 5, this is
      explained as resulting from formation of a nonactive dimer, formulated as a bis
      mu-methoxide-bridged form (L:Zn(2+)((-)OCH(3))(2)Zn(2+):L) in equilibrium with an
      active monomeric form (L:Zn(2+)((-)OCH(3))). In the case of the Zn(2+):6 system,
      no dimeric forms are present as can be judged by the strict linearity of the
      plots of k(obs) vs [Zn(2+)](total) in the presence of equimolar 6 and (-)OCH(3).
      Analysis of the potentiometric titration curves for Zn(2+) alone and in the
      presence of the ligands allows calculation of the speciation of the various
      Zn(2+) forms and shows that the binding to ligands 4 and 6 is very strong, while
      the binding to ligand 5 is weaker. Overall the best catalytic system is provided
      by equimolar Zn(2+), 5, and (-)OCH(3), which exhibits excellent turnover of the
      methanolysis of paraoxon when the substrate is in excess. At a concentration of 2
      mM in each of these components, which sets the pH of the solution at 9.5, the
      acceleration of the methanolysis of paraoxon and fenitrothion relative to the
      methoxide reaction is 1.8 x 10(6)-fold and 13 x 10(6)-fold, respectively. A
      mechanism for the catalyzed reactions is proposed which involves a dual role for
      the metal ion as a Lewis acid and source of nucleophilic Zn(2+)-bound (-)OCH(3).

PMID- 15476376
TI  - Fine tuning of the electronic coupling between metal centers in cyano-bridged
      mixed-valent trinuclear complexes.
AB  - We report the synthesis, characterization, and spectroscopic properties of a
      family of trinuclear cyano-bridged mixed-valent compounds, trans
      [Ru(II)L(4)[NCFe(III)(CN)(5)](2)](4-), trans-[Ru(II)L(4)[CNFe(III)(CN)(5)](2)](4
      ), and cis-[Ru(II)(bpy)(2)[NCFe(III)(CN)(5)](2)](4-) (L = pyridine, 4-tert
      butylpyridine, and 4-methoxypyridine). Tetraphenylphosphonium salts of complexes
      trans-[Ru(II)L(4)[NCFe(III)(CN)(5)](2)](4-) (L = pyridine and 4-tert
      butylpyridine) crystallize in the space groups C2 and P2(1)/c, respectively, and
      show a linear arrangement of the metal units and an almost completely eclipsed
      configuration of the equatorial ligands. An intense band (epsilon approximately
      2000-9000 M(-1) cm(-1)) is observed for all of the compounds in the NIR region of
      the spectrum, not present in the separated building blocks, and strongly solvent
      dependent. We assign it as a metal-to-metal charge transfer (MMCT) from the
      Ru(II) to the terminal Fe(III) moieties in the context of a simplified three
      center model. The electrochemistry measurements reveal a splitting of the redox
      waves for the reduction of the iron centers for some of the complexes with a
      trans configuration between the metal units, ranging from 100 to 260 mV,
      depending on the substituting pyridine ligand and the solvent, suggesting long
      range metal-metal interactions. These interactions are rationalized in terms of
      the energy matching between the pi-symmetry orbitals of the metals and the
      cyanide bridge. The one- and two-electron reduced species derived from compounds
      trans-[Ru(II)L(4)[NCFe(III)(CN)(5)](2)](4-,5-,6-) were characterized in
      methanolic solution. The mixed-valent Fe(II)-Ru(II)-Fe(III) system exhibits an
      intense red shifted band in the NIR region of the spectrum, arising from the
      superposition of MMCT bands from the central Ru(II) to the terminal Fe(III)
      fragments and from the 1 nm distant Fe(II) to Fe(III) centers.

PMID- 15476377
TI  - ZP8, a neuronal zinc sensor with improved dynamic range; imaging zinc in
      hippocampal slices with two-photon microscopy.
AB  - The synthesis of a difluorofluorescein monocarboxaldehyde platform and its use
      for preparing ZP8, a new member of the Zinpyr family of neuronal Zn(2+) sensors,
      are described. By combining an aniline photoinduced electron transfer (PET)
      switch and an electron-withdrawing fluorescein scaffold, ZP8 displays reduced
      background fluorescence and improved dynamic range compared to previous ZP
      probes. The bright sensor undergoes an 11-fold increase in fluorescence intensity
      upon Zn(2+) complexation (Phi = 0.03-0.35) with high selectivity over cellular
      concentrations of Ca(2+) and Mg(2+). In addition, sensors in the ZP family have
      been utilized for optical imaging in biological samples using two-photon
      microscopy (TPM). The cell-permeable ZP3 probe is capable of identifying natural
      pools of labile Zn(2+) within the mossy fiber synapses of live hippocampal slices
      using TPM, establishing the application of this technique for monitoring
      endogenous Zn(2+) stores.

PMID- 15476378
TI  - Acidities of platinum(II) mu-hydroxo complexes bearing diphosphine ligands.
AB  - The pK(a) values in DMSO of the monoprotic complexes [(L(2)Pt)(2)(mu-OH)(mu
      NMePh)](2+) (4) (L(2) = Ph(2)PCH(2)CH(2)PPh(2) (dppe), Ph(2)PCMe(2)PPh(2)
      (dppip)) are 11.9 +/- 0.1 (L(2) = dppe) and 13.5 +/- 0.2 (L(2) = dppip) as
      determined by (31)P NMR equilibrium titration with bases of known pK(a).
      Complexes 4 were prepared by treatment of [L(2)Pt(mu-OH)](2)(2+) (1) with N
      methylaniline. The oxo complexes [(L(2)Pt)(2)(mu-O)(mu-NMePh)](+), formed in the
      equilibrium titration reactions, were independently synthesized in THF by
      deprotonation of [(L(2)Pt)(2)(mu-OH)(mu-NMePh)](2+) with NaN(SiMe(3))(2) and
      characterized as NaBF(4) adducts. Similar experiments with diprotic [L(2)Pt(mu
      OH)](2)(2+) (L(2) = dppe, Ph(2)PCH(2)CH(2)CH(2)PPh(2) (dppp)) were complicated by
      exchange processes and were less conclusive, giving pK(a1) < 18 and pK(a2) > 18
      in DMSO.

PMID- 15476379
TI  - Terminal titanium-ligand multiple bonds. Cleavages of C=O and C=S double bonds
      with Ti imido complexes.
AB  - Treatment of (t-)BuN=TiCl(2)Py(3) with 2 equiv lithium ketiminate compound,
      Li[OCMeCHCMeN(Ar)] (where Ar = 2,6-diisopropylphenyl), in toluene at room
      temperature gave (t-)BuN=Ti[OCMeCHCMeN(Ar)](2) (1) in high yield. The reaction of
      1 with phenyl isocyanate at room-temperature resulted in imido ligand exchange
      producing PhN=Ti[OCMeCHCMeN(Ar)](2) (2). Compound 1 decomposed at 90 degrees C to
      form a terminal titanium oxo compound O=Ti[OCMeCHCMeN(Ar)](2) (3) and (t
      )BuNHCMeCHCMeNAr (4). Also, the compound 3 could be obtained by reacting 1 with
      CO(2) under mild condition. Similarly, while 1 reacts with an excess of carbon
      disulfide, a novel terminal titanium sulfido compound S=Ti[OCMeCHCMeN(Ar)](2) (5)
      was formed via a C=S bond breaking reaction. A novel titanium isocyanate compound
      Ti[OCMeCHCMeN(Ar)](2)(NCO)(OEt) (6) was formed on heating 1 with 1 equiv of
      urethane, H(2)NCOOEt. Compounds 1-6 have been characterized by (1)H and (13)C NMR
      spectroscopies. The molecular structures of 1, 3, 5, and 6 were determined by
      single-crystal X-ray diffraction. A theoretical calculation predicted that the
      cleavage of the C-S double bonds for carbon disulfide with the Ti=N bond of
      compound 1 was estimated at ca. 21.8 kcal.mol(-1) exothermic.

PMID- 15476380
TI  - Structures and properties of ruthenium(II) complexes of pyridylamine ligands with
      oxygen-bound amide moieties: regulation of structures and proton-coupled electron
      transfer.
AB  - Tris(2-pyridylemthyl)amine (TPA) derivatives having two amide moieties at the 6
      positions of the two pyridine rings of TPA and their Ru(II) complexes were
      synthesized and characterized by spectroscopic methods, X-ray crystallography,
      and electrochemical measurements. The complexes prepared were [RuCl(L)]PF(6) (L =
      N,N-bis(6-(1-naphthoylamide)-2-pyridylmethyl)-N-(2-pyridylmethyl)amine (1), N,N
      bis(6-(2-naphthoylamide)-2-pyridylmethyl)-N-(2-pyridylmethyl)amine (2), N,N-bis(6
      (isobutyrylamide)-2-pyridylmethyl)-N-(2-pyridylmethyl)amine (3)); the crystal
      structures of the three compounds were established by X-ray crystallography. In
      variable-temperature (1)H NMR spectra of 1 and 2 in CD(3)CN solutions, the pi-pi
      stacking in 1 was too rigid to exhibit any fluxional motions in NMR measurements;
      however, the pi-pi stacking of 2 was weaker and showed fluxional behavior in
      nearly T-shaped pi-pi interaction for the 2-naphthly groups (DeltaH degrees = 
      2.3 kJ mol(-1); DeltaG degrees = -0.9 kJ mol(-1) and DeltaS degrees = -7.7 J mol(
      1) K(-1) at 233 K in CD(3)CN). For each of these three complexes, one of the
      amide moieties coordinated to the Ru(II) center through an amide oxygen. The
      other uncoordinated amide N-H formed intramolecular hydrogen bonding which
      remained intact even in aqueous media, indicating the intramolecular hydrogen
      bonding was geometrically compelled to form. The amide coordination is also
      stabilized and strengthened by the hydrogen bonding, so that the structure of
      each compound is maintained in solution. It is suggested that this hydrogen
      bonding lowers the redox potentials of the Ru(II) centers due to polarization of
      the coordinated amide C=O bond, in which the oxygen atom becomes more
      electrostatically negative and its electron-donating ability is strengthened. The
      N-H protons in the coordinated amide moieties were found to undergo a reversible
      deprotonation-protonation process, and the redox potentials of the Ru(II) centers
      could be regulated in the range of 500 mV in CH(3)CN solutions. The Pourbaix
      diagram for 1 clearly showed that this proton-coupled redox behavior is a one
      electron/one-proton process, and the pK(a) value was estimated to be
      approximately 6.

PMID- 15476381
TI  - Functional superoxide dismutase mimics. Structural characterization and magnetic
      exchange interactions of copper(II)-N-substituted sulfonamide dimer complexes.
AB  - Dinuclear copper(II) complexes with N-substituted sulfonamide ligands as
      superoxide dismutase (SOD) mimics have been investigated. The new N-(thiazol-2
      yl)toluenesulfonamide (Htz-tol) and N-(thiazol-2-yl)naphthalenesulfonamide (Htz
      naf) ligands have been prepared and structurally characterized. The complexes
      derived from these ligands, [Cu(2)(tz-tol)(4)] (1) and [Cu(2)(tz-naf)(4)] (2),
      have been synthesized, and their crystal structure, magnetic properties, and EPR
      spectra were studied in detail. In both compounds the metal centers are bridged
      by four nonlinear triatomic NCN groups. The coordination geometry of the coppers
      in the dinuclear entity of 1 and 2 is distorted square planar with two N-thiazole
      and two N-sulfonamido atoms. Magnetic susceptibility data show a strong
      antiferromagnetic coupling, with -2J = 121.3 cm(-1) for compound 1 and -2J =
      104.3 cm(-1) for compound 2. The EPR spectra of the polycrystalline samples of
      compounds 1 and 2 have been measured at the X- and Q-band frequencies at
      different temperatures. Above 20 K the spectra are characteristic of S = 1
      species with zero-field splitting parameter D = 0.230 cm(-1) for compound 1 and
      0.229 cm(-1) for compound 2. The EPR parameters are discussed in terms of the
      known binuclear structures. The complexes exhibit high SOD activity, as shown by
      the low IC(50) values obtained with the xanthine/xanthine oxidase/NBT assay: 0.13
      microM for compound 1; 0.17 microM for compound 2.

PMID- 15476382
TI  - Organometallic derivatives of fullerenes: a DFT study of (eta2-Cx)[Pt(PH3)2]n (x
      = 60, 70, 84; n = 1-6).
AB  - To determine the relationship among curvature, patch type, and reactivity of the
      C-C site, a series of density functional calculations were performed on several
      substituted fullerenes. [6:6] pyracylene-type sites are the most reactive sites
      in all analyzed cages: C(60), C(70), and C(84). The binding energy between the
      Pt(PH(3))(2) unit and fullerene is almost independent of the size of the cage and
      of the number of metals coordinated on the fullerene surface. Contrarily,
      curvature and type of carbon-carbon bond are determinant for the coordination
      strength. The use of relatively large basis sets is necessary to have consistent
      energies.

PMID- 15476383
TI  - A new tridentate pincer phosphine/n-heterocyclic carbene ligand: palladium
      complexes, their structures, and catalytic activities.
AB  - A new imidazolium salt, 1,3-bis(2-diphenylphosphanylethyl)-3H-imidazol-1-ium
      chloride (2), for the phosphine/N-heterocyclic carbene-based pincer ligand,
      PC(NHC)P, and its palladium complexes were reported. The complex,
      [Pd(PC(NHC)P)Cl]Cl (4), was prepared by the common route of silver carbene
      transfer reaction and a novel direct reaction between the ligand precursor,
      PC(NHC)P.HCl and PdCl(2) without the need of a base. Metathesis reactions of 4
      with AgBF(4) in acetonitrile produced [Pd(PC(NHC)P)(CH(3)CN)](BF(4))(2) (5). The
      same reaction in the presence of excess pyridine gave
      [Pd(PC(NHC)P)(py)](BF(4))(2) (6). The X-ray structure determination on 4-6
      revealed the chiral twisting of the central imidazole rings from the metal
      coordination plane. In solution, fast interconversion between left- and right
      twisted forms occurs. The twisting reflects the weak pi-accepting property of the
      central NHC in PC(NHC)P. The uneven extent of twisting among the three complexes
      further implies the low rotational barrier about the Pd-NHC bond. Related
      theoretical computations confirm the small rotational energy barrier about the Pd
      NHC bond (ca. 4 kcal/mol). Catalytic applications of 4 and 5 have shown that the
      complexes are modest catalysts in Suzuki coupling. The complexes were active
      catalysts in Heck coupling reactions with the dicationic complex 5 being more
      effective than the monocationic complex 4.

PMID- 15476384
TI  - Crystal structures of Sr4Sn2Se9 and Sr4Sn2Se10 and the oxidation state of tin in
      an unusual geometry.
AB  - The new ternary selenostannates Sr(4)Sn(2)Se(9) and Sr(4)Sn(2)Se(10) have been
      synthesized by heating the elements at 1023 K in an argon atmosphere. Their
      structures were determined by single-crystal X-ray methods. Sr(4)Sn(2)Se(9)
      crystallizes in a new structure type (Pbam, a = 12.042(2) A, b = 16.252(3) A, c =
      8.686(2) A, Z = 4) with Sn(2)Se(6)(4-), SnSe(4)(4-), and Se(2)(2-) subunits.
      Sr(4)Sn(2)Se(10) (P2(1)2(1)2, a = 12.028(2) A, b = 16.541(3) A, c = 8.611(2) A, Z
      = 4) has a similar structure with Se(3)(2-) triangles instead of Se(2)(2-)
      dumbbells. Strontium is 8-fold-coordinated by selenium in both cases. The opening
      angles between tin and the terminal selenium atoms in the Sn(2)Se(6) subunits are
      close to 160 degrees , which is nearer a typical Sn(2+) coordination geometry
      than classical SnSe(4) tetrahedra. This result suggests the tin oxidation state
      in the Sn(2)Se(6) units to be lower than the expected Sn(4+). This question is
      examined by self-consistent LMTO and LAPW band structure calculations expanded by
      the Bader analysis of the charge density to assign reliable atomic charges.

PMID- 15476385
TI  - Rhodium-hydrido-benzylamine-triphenylphosphine complexes: solid-state and
      solution structures and implications in catalyzed imine hydrogenation.
AB  - The complexes cis,trans,cis-[Rh(H)(2)(PPh(3))(2)(NH(2)CH(2)Ph)(2)]PF(6) (1) and
      cis-[Rh(PPh(3))(2)(NH(2)CH(2)Ph)(2)]PF(6) (2) are characterized by X-ray
      crystallography; the structures are maintained in CH(2)Cl(2) where the species
      are in equilibrium under H(2). In MeOH and in acetone, loss of amine and/or H(2)
      can occur. Traces of 1 and 2 are present after a Rh-catalyzed H(2)-hydrogenation
      of PhCH=NCH(2)Ph in MeOH, where the amine is generated by hydrolysis of the imine
      substrate through adventitious water. The findings are relevant to catalyst
      poisoning in the catalytic process.

PMID- 15476386
TI  - An unusual open cubane structure in a mu(1,1)-azido- and alkoxo-bridged
      tetranuclear copper(II) complex, [Cu4L2(mu(1,1)-N3)2].5H2O (H3L = N,N'-(2
      Hydroxylpropane-1,3-diyl)bis-salicylideneimine).
AB  - A new end-on (EO) azido-bridged tetranuclear copper(II) complex
      [Cu(4)L(2)(mu(1,1)-N(3))(2)].5H(2)O derived from the ligand H(3)L (N,N'-(2
      hydroxylpropane-1,3-diyl)bis-salicylideneimine) has been synthesized. Its X-ray
      structure shows an unusual Cu(4)O(2)N(2) open cubane core in which four
      copper(II) atoms are connected two by two through two mu(1,1)-azido species and
      three by three through two alkoxo bridges. The magnetic susceptibility data is
      dominated by strong antiferromagnetic interactions associated with the alkoxides
      and weak ferromagnetic interactions arising from the azides, in agreement with
      magneto-structural correlations found in the literature relative to such bridges
      in Cu(II) complexes.

PMID- 15476387
TI  - Studies on the formation of glutathionylcobalamin: any free intracellular
      aquacobalamin is likely to be rapidly and irreversibly converted to
      glutathionylcobalamin.
AB  - A decade ago Jacobsen and co-workers reported the first evidence for the presence
      of glutathionylcobalamin (GSCbl) in mammalian cells and suggested that it could
      in fact be a precursor to the formation of the two coenzyme forms of vitamin
      B(12), adenosylcobalamin and methylcobalamin (Pezacka et al. Biochem. Biophys.
      Res. Commun. 1990, 169, 443). It has also recently been proposed by McCaddon and
      co-workers that GSCbl may be useful for the treatment of Alzheimer's disease
      (McCaddon et al. Neurology 2002, 58, 1395). Aquacobalamin is one of the major
      forms of vitamin B(12) isolated from mammalian cells, and high concentrations of
      glutathione (1-10 mM) are also found in cells. We have now determined observed
      equilibrium constants, K(obs)(GSCbl), for the formation of GSCbl from
      aquacobalamin and glutathione in the pH range 4.50-6.00. K(obs)(GSCbl) increases
      with increasing pH, and this increase is attributed to increasing amounts of the
      thiolate forms (RS(-)) of glutathione. An estimate for the equilibrium constant
      for the formation of GSCbl from aquacobalamin and the thiolate forms of
      glutathione of approximately 5 x 10(9) M(-1) is obtained from the data. Hence,
      under biological conditions the formation of GSCbl from aquacobalamin and
      glutathione is essentially irreversible. The rate of the reaction between
      aquacobalamin/hydroxycobalamin and glutathione for 4.50 < pH < 11.0 has also been
      studied and the observed rate constant for the reaction was found to decrease
      with increasing pH. The data were fitted to a mechanism in which each of the 3
      macroscopic forms of glutathione present in this pH region react with
      aquacobalamin, giving k(1) = 18.5 M(-1) s(-1), k(2) = 28 +/- 10 M(-1) s(-1), and
      k(3) = 163 +/- 8 M(-1) s(-1). The temperature dependence of the observed rate
      constant at pH 7.40 ( approximately k(1)) was also studied, and activation
      parameters were obtained typical of a dissociative process (DeltaH++ = 81.0 +/-
      0.5 kJ mol(-1) and DeltaS++ = 48 +/- 2 J K(-1) mol(-1)). Formation of GSCbl from
      aquacobalamin is rapid; for example, at approximately 5 mM concentrations of
      glutathione and at 37 degrees C, the half-life for formation of GSCbl from
      aquacobalamin and glutathione is 2.8 s. On the basis of our equilibrium and rate
      constant data we conclude that, upon entering cells, any free (protein-unbound)
      aquacobalamin could be rapidly and irreversibly converted to GSCbl. GSCbl may
      indeed play an important role in vitamin B(12)-dependent processes.

PMID- 15476389
TI  - Preventing misfolding of the prion protein by trimethylamine N-oxide.
AB  - Transmissible spongiform encephalopathies are a class of fatal neurodegenerative
      diseases linked to the prion protein. The prion protein normally exists in a
      soluble, globular state (PrP(C)) that appears to participate in copper metabolism
      in the central nervous system and/or signal transduction. Infection or disease
      occurs when an alternatively folded form of the prion protein (PrP(Sc)) converts
      soluble and predominantly alpha-helical PrP(C) into aggregates rich in beta
      structure. The structurally disordered N-terminus adopts beta-structure upon
      conversion to PrP(Sc) at low pH. Chemical chaperones, such as trimethylamine N
      oxide (TMAO), can prevent formation of PrP(Sc) in scrapie-infected mouse
      neuroblastoma cells [Tatzelt, J., et al. (1996) EMBO J. 15, 6363-6373]. To
      explore the mechanism of TMAO protection of PrP(C) at the atomic level, molecular
      dynamics simulations were performed under conditions normally leading to
      conversion (low pH) with and without 1 M TMAO. In PrP(C) simulations at low pH,
      the helix content drops and the N-terminus is brought into the small native beta
      sheet, yielding a PrP(Sc)-like state. Addition of 1 M TMAO leads to a decreased
      radius of gyration, a greater number of protein-protein hydrogen bonds, and a
      greater number of tertiary contacts due to the N-terminus forming an Omega-loop
      and packing against the structured core of the protein, not due to an increase in
      the level of extended structure as with the PrP(C) to PrP(Sc) simulation. In
      simulations beginning with the "PrP(Sc)-like" structure (derived from PrP(C)
      simulated at low pH in pure water) in 1 M TMAO, similar structural reorganization
      at the N-terminus occurred, disrupting the extended sheet. The mechanism of
      protection by TMAO appears to be exclusionary in nature, consistent with previous
      theoretical and experimental studies. The TMAO-induced N-terminal conformational
      change prevents residues that are important in the conversion of PrP(C) to
      PrP(Sc) from assuming extended sheet structure at low pH.

PMID- 15476390
TI  - Transient aggregation and stable dimerization induced by introducing an Alzheimer
      sequence into a water-soluble protein.
AB  - Transient contacts between denatured polypeptide chains are likely to play an
      important part in the initial stages of protein aggregation and fibrillation. To
      analyze the nature of such contacts, we have carried out a protein engineering
      study of the 102-residue protein U1A, which aggregates transiently in the wild
      type form during refolding from the guanidinium chloride-denatured state. We have
      prepared a series of mutants with increased aggregation tendencies by increasing
      the homology between two beta-strands of U1A and the Alzheimer peptide (beta-AP).
      These mutants undergo transient aggregation during refolding, as measured by
      concentration dependence, double-jump experiments, and binding of ANS, a probe
      for exposed hydrophobic patches on protein surfaces. The propensity to aggregate
      increases with increasing homology to beta-AP. Further, the degree of transient
      ANS binding correlates reasonably well with the structural parameters recently
      shown to play a role in the fibrillation of natively unfolded proteins. Two
      mutants highly prone to transient aggregation, U1A-J and U1A-G, were also studied
      by NMR. Secondary structural elements of the U1A-J construct (with lower beta-AP
      homology) are very similar to those observed in U1A-wt. In contrast, the high
      homology construct U1A-G exhibits local unfolding of the C-terminal helix, which
      packs against the beta-sheet in the wild-type protein. U1A-G is mainly dimeric
      according to (15)N spin relaxation data, and the dimer interface most likely
      involves the beta-sheet. Our data suggest that the transient aggregate relies on
      specific intermolecular interactions mediated by structurally flexible regions
      and that contacts may be formed in different beta-strand registers.

PMID- 15476391
TI  - Overexpression, purification, and characterization of ProQ, a posttranslational
      regulator for osmoregulatory transporter ProP of Escherichia coli.
AB  - ProP is an osmosensor and osmoregulatory transporter in Escherichia coli. Osmotic
      activation of ProP is attenuated 5-fold in the absence of soluble protein ProQ,
      but proQ lesions do not influence proP transcription or ProP levels. The
      mechanism by which ProQ amplifies ProP activity is unknown. Putative proQ
      orthologues are found in Gram-negative bacteria (only), but none have known
      functions. ProQ was overexpressed to low and high levels with and without a C
      terminal histidine tag (His(6)). Plasmid-encoded ProQ or ProQ-His(6) complemented
      in-frame chromosomal deletion DeltaproQ676, restoring ProP activity. After
      overexpression, both proteins were poorly soluble unless cells were lysed in
      media of high salinity. ProQ copurified with DNA binding proteins of similar size
      (HU and a histone-like protein) by ion exchange and exclusion chromatographies,
      whereas ProQ-His(6) could be purified to homogeneity by nickel chelate affinity
      chromatography. Sequence-based analysis and modeling suggest that ProQ includes
      distinct N- and C-terminal domains linked by an unstructured sequence. The N
      terminal domain can be modeled on the crystal structure of alpha-helical RNA
      binding protein FinO, whereas the C-terminal domain can be modeled on an SH3-like
      domain (beta-structure). Both ProQ and ProQ-His(6) appeared to be monomeric,
      though the higher Stokes radius of ProQ-His(6) may reflect altered domain
      interactions. The measured secondary structure content of ProQ (circular
      dichroism (CD) spectroscopy) contrasted with sequence-based prediction but was as
      expected if the spectrum of the C-terminal domain is analogous to those reported
      for SH3 domains. The CD spectrum of ProQ was pH- but not NaCl-sensitive.

PMID- 15476392
TI  - Multiple active site conformations revealed by distant site mutation in ornithine
      decarboxylase.
AB  - Ornithine decarboxylase (ODC) is an obligate homodimer that catalyzes the
      pyridoxal 5'-phosphate-dependent decarboxylation of l-ornithine to putrescine, a
      vital step in polyamine biosynthesis. A previous mutagenic analysis of the ODC
      dimer interface identified several residues that were distant from the active
      site yet had a greater impact on catalytic activity than on dimer stability
      [Myers, D. P., et al. (2001) Biochemistry 40, 13230-13236]. To better understand
      the basis of this phenomenon, the structure of the Trypanosoma brucei ODC mutant
      K294A was determined to 2.15 A resolution in complex with the substrate analogue
      d-ornithine. This residue is distant from the reactive center (>10 A from the PLP
      Schiff base), and its mutation reduced catalytic efficiency by 3 kcal/mol. The X
      ray structure demonstrates that the mutation increases the disorder of residues
      Leu-166-Ala-172 (Lys-169 loop), which normally form interactions with Lys-294
      across the dimer interface. In turn, the Lys-169 loop forms interactions with the
      active site, suggesting that the reduced catalytic efficiency is mediated by the
      decreased stability of this loop. The extent of disorder varies in the four Lys
      169 loops in the asymmetric unit, suggesting that the mutation has led to an
      increase in the population of inactive conformations. The structure also reveals
      that the mutation has affected the nature of the ligand-bound species. Each of
      the four active sites contains unusual ligands. The electron density suggests one
      active site contains a gem-diamine intermediate with d-ornithine; the second has
      density consistent with a tetrahedral adduct with glycine, and the remaining two
      contain tetrahedral adducts of PLP, Lys-69, and water (or hydroxide). These data
      also suggest that the structure is less constrained in the mutant enzyme. The
      observation of a gem-diamine intermediate provides insight into the
      conformational changes that occur during the ODC catalytic cycle.

PMID- 15476393
TI  - Schistosoma mansoni fatty acid binding protein: specificity and functional
      control as revealed by crystallographic structure.
AB  - Schistosoma mansoni fatty acid binding protein (Sm14) was crystallized with bound
      oleic acid (OLA) and arachidonic acid (ACD), and their structures were solved at
      1.85 and 2.4 A resolution, respectively. Sm14 is a vaccine target for
      schistosomiasis, the second most prevalent parasitic disease in humans. The
      parasite is unable to synthesize fatty acids depending on the host for these
      nutrients. Moreover, arachidonic acid (ACD) is required to synthesize
      prostaglandins employed by schistosomes to evade the host's immune defenses. In
      the complex, the hydrocarbon tail of bound OLA assumes two conformations, whereas
      ACD adopts a unique hairpin-looped structure. ACD establishes more specific
      interactions with the protein, among which the most important is a pi-cation bond
      between Arg78 and the double bond at C8. Comparison with homologous fatty acid
      binding proteins suggests that the binding site of Sm14 is optimized to fit ACD.
      To test the functional implications of our structural data, the affinity of Sm14
      for 1,8-anilinonaphthalenesulfonic acid (ANS) has been measured; moreover the
      binding constants of six different fatty acids were determined from their ability
      to displace ANS. OLA and ACD exhibited the highest affinities. To determine the
      rates of fatty acid binding and dissociation we carried out stopped flow kinetic
      experiments monitoring displacement by (and of) ANS. The binding rate constant of
      ligands is controlled by a slow pH dependent conformational change, which we
      propose to have physiological relevance.

PMID- 15476394
TI  - Hydrogen bonding on the ice-binding face of a beta-helical antifreeze protein
      indicated by amide proton NMR chemical shifts.
AB  - The dependence of amide proton chemical shifts on temperature is used as an
      indication of the hydrogen bonding properties in a protein. The amide proton
      temperature coefficients of the beta-helical antifreeze protein from Tenebrio
      molitor are examined to determine their hydrogen bonding state in solution. The
      temperature-dependent chemical shift behavior of the amides in T. molitor
      antifreeze protein varies widely throughout the protein backbone; however, very
      subtle effects of hydrogen bonding can be distinguished using a plot of chemical
      shift deviation (CSD) versus the backbone amide chemical shift temperature
      gradient (Deltadelta/DeltaT). We show that differences between the two ranks of
      ice-binding threonine residues on the surface of the protein indicate that
      threonine residues in the left-hand rank participate in intrastrand hydrogen
      bonds that stabilize the flat surface required for optimal ice binding.

PMID- 15476395
TI  - Rate-temperature relationships in lambda-repressor fragment lambda 6-85 folding.
AB  - Two classes of lambda(6-85) mutants (those richer in alanine, and those richer in
      glycine) have very similar slopes in an Arrhenius plot of the unfolding rates but
      very different temperature dependencies of the folding rates. Temperature
      dependent interactions (e.g., hydrophobicity) play a large role in the initial
      stages of folding but not in the initial stages of unfolding of lambda(6-85).
      Placement of the transition state in terms of its surface exposure and entropy
      shows that at least two reaction coordinates are required to describe folding of
      all mutants over the full temperature range. The unusual Arrhenius plots of the
      very fastest mutant provide an additional kinetic signature for downhill folding.

PMID- 15476396
TI  - Characterization of Sac10a, a hyperthermophile DNA-binding protein from
      Sulfolobus acidocaldarius.
AB  - Sac10a is a member of a group of basic DNA-binding proteins thought to be
      important in chromatin structure and regulation in the archaeon Sulfolobus. We
      describe here the isolation, gene identification, and biophysical
      characterization of native Sac10a. The protein exists as a 23.8 kDa homodimer at
      pH 7 and unfolds with a T degrees of 122 degrees C. Dissociation of the dimer
      into folded globular subunits is promoted by decreased pH and salt concentration.
      Thermal unfolding of the monomeric subunits occurred with two transitions,
      indicating two independent domains. The dimer demonstrated a high affinity for
      duplex poly(dAdT) with a K(D) of 5 x 10(-)(10) M and a site size of 17 bp (in
      0.15 M KCl, pH 7), with only weak binding (K(D) > 5 x 10(-)(6) M) to poly(dA)
      poly(dT), poly(dGdC), poly(dG)-poly(dC), and Escherichia coli DNA under similar
      conditions. Binding to poly(dAdT) resulted in distortions in the DNA duplex that
      were consistent with overwinding as indicated by inversion of the CD spectrum of
      the DNA. The monomeric subunits are predicted to adopt a winged helix DNA-binding
      motif which dimerizes through formation of a two-stranded coiled coil involving
      an extended C-terminal helix with more than four heptad repeats (about 45 A in
      length). This is the first example of the conserved archaeal transcription
      regulator domain COG3432 to be characterized. Sequences for homologous proteins
      containing both COG3432 and predicted coiled coil domains occur in the genomes of
      both crenarchaeota (Sulfolobus, Pyrobaculum, Aeropyrum) and euryarchaeota
      (Methanosarcina, Methanococcus, Archaeoglobus, Thermoplasma), with multiple genes
      in some species. Sac10a shows no sequence similarity to the other Sulfolobus
      chromatin proteins Sac7d, Sac8, Sso10b2, and Alba.

PMID- 15476397
TI  - Phosphoenolpyruvate- and ATP-dependent dihydroxyacetone kinases: covalent
      substrate-binding and kinetic mechanism.
AB  - Dihydroxyacetone (Dha) kinases are a sequence-conserved family of enzymes, which
      utilize two different phosphoryldonors, ATP in animals, plants, and some
      bacteria, and a multiphosphoprotein of the phosphoenolpyruvate carbohydrate
      phosphotransferase system (PTS) in most bacteria. Here, we compare the PTS
      dependent kinase of Escherichia coli and the ATP-dependent kinase of Citrobacter
      freundii. They display 30% sequence identity. The binding constants of the E.
      coli kinase for eleven short-chain carbonyl compounds were determined by acetone
      precipitation of the enzyme-substrate complexes. They are 3.4 microM for Dha, 780
      microM for Dha-phosphate (DhaP), 50 microM for D,L-glyceraldehyde (GA), and 90
      microM for D,L-glyceraldehyde-3-phosphate. The k(cat) for Dha of the PTS
      dependent kinase is 290 min(-1), and that of the ATP-dependent kinase is 1050
      min(-1). The Km for Dha of both kinases is <6 microM. The X-ray structures of the
      enzyme-GA and the enzyme-DhaP complex show that substrates as well as products
      are bound in hemiaminal linkage to an active-site histidine. Quantum-mechanical
      calculations offer no indication for activation of the reacting hydroxyl group by
      the formation of the hemiaminal. However, the formation of the hemiaminal bond
      allows selection for short-chain carbonyl compounds and discrimination against
      structurally similar polyols. The Dha kinase remains fully active in the presence
      of 2 M glycerol, and phosphorylates trace impurities of carbonyl compounds
      present in glycerol.

PMID- 15476398
TI  - Solution structure of the apo and copper(I)-loaded human metallochaperone HAH1.
AB  - The human metallochaperone HAH1 has been produced in Escherichia coli with four
      additional amino acids at the C-terminus and characterized in solution by NMR
      spectroscopy, both with and without copper(I). The solution structure of the apo
      HAH1 monomer has a root-mean-square-deviation (RMSD) of 0.50 A for the
      coordinates of the backbone atoms and 0.96 A for all heavy atoms. These values
      compare, respectively, with 0.45 and 0.95 A for copper(I)-HAH1. There are only
      minor structural rearrangements upon copper(I) binding. In particular, the
      variation of interatomic interactions around the metal-binding region is limited
      to a movement of Lys60 toward the metal site. The protein structures are similar
      to those obtained by X-ray crystallography in a variety of derivatives, with
      backbone RMSD values below 1 A. In the holoprotein, copper(I) is confirmed to be
      two coordinated. If these data are compared with those of orthologue proteins, we
      learn that HAH1 has a lower tendency to change coordination number from two to
      three. Such a switch in coordination is a key step in copper transfer.

PMID- 15476399
TI  - Mutational analysis of the nuclease domain of Escherichia coli ribonuclease III.
      Identification of conserved acidic residues that are important for catalytic
      function in vitro.
AB  - The ribonuclease III superfamily represents a structurally distinct group of
      double-strand-specific endonucleases with essential roles in RNA maturation, RNA
      decay, and gene silencing. Bacterial RNase III orthologs exhibit the simplest
      structures, with an N-terminal nuclease domain and a C-terminal double-stranded
      RNA-binding domain (dsRBD), and are active as homodimers. The nuclease domain
      contains conserved acidic amino acids, which in Escherichia coli RNase III are
      E38, E41, D45, E65, E100, D114, and E117. On the basis of a previously reported
      crystal structure of the nuclease domain of Aquifex aeolicus RNase III, the E41,
      D114, and E117 side chains of E. coli RNase III are expected to be coordinated to
      a divalent metal ion (Mg(2+) or Mn(2+)). It is shown here that the RNase
      III[E41A] and RNase III[D114A] mutants exhibit catalytic activities in vitro in
      10 mM Mg(2+) buffer that are comparable to that of the wild-type enzyme. However,
      at 1 mM Mg(2+), the activities are significantly lower, which suggests a weakened
      affinity for metal. While RNase III[E41A] and RNase III[D114A] have K(Mg) values
      that are approximately 2.8-fold larger than the K(Mg) of RNase III (0.46 mM), the
      RNase III[E41A/D114A] double mutant has a K(Mg) of 39 mM, suggesting a redundant
      function for the two side chains. RNase III[E38A], RNase III[E65A], and RNase
      III[E100A] also require higher Mg(2+) concentrations for optimal activity, with
      RNase III[E100A] exhibiting the largest K(Mg). RNase III[D45A], RNase III[D45E],
      and RNase III[D45N] exhibit negligible activities, regardless of the Mg(2+)
      concentration, indicating a stringent functional requirement for an aspartate
      side chain. RNase III[D45E] activity is partially rescued by Mn(2+). The
      potential functions of the conserved acidic residues are discussed in the context
      of the crystallographic data and proposed catalytic mechanisms.

PMID- 15476400
TI  - Tryptophan 500 and arginine 707 define product and substrate active site binding
      in soybean lipoxygenase-1.
AB  - There is much debate whether the fatty acid substrate of lipoxygenase binds
      "carboxylate-end first" or "methyl-end first" in the active site of soybean
      lipoxygenase-1 (sLO-1). To address this issue, we investigated the sLO-1 mutants
      Trp500Leu, Trp500Phe, Lys260Leu, and Arg707Leu with steady-state and stopped-flow
      kinetics. Our data indicate that the substrates (linoleic acid (LA), arachidonic
      acid (AA)), and the products (13-(S)-hydroperoxy-9,11-(Z,E)-octadecadienoic acid
      (HPOD) and 15-(S)-hydroperoxyeicosatetraeonic acid (15-(S)-HPETE)) interact with
      the aromatic residue Trp500 (possibly pi-pi interaction) and with the positively
      charged amino acid residue Arg707 (charge-charge interaction). Residue Lys260 of
      soybean lipoxygenase-1 had little effect on either the activation or steady-state
      kinetics, indicating that both the substrates and products bind "carboxylate-end
      first" with sLO-1 and not "methyl-end first" as has been proposed for human 15
      lipoxygenase.

PMID- 15476401
TI  - Identification of the protein binding region of S-trityl-L-cysteine, a new potent
      inhibitor of the mitotic kinesin Eg5.
AB  - Human Eg5, a mitotic motor of the kinesin superfamily, is involved in the
      formation and maintenance of the mitotic spindle. The recent discovery of small
      molecules that inhibit HsEg5 by binding to its catalytic motor domain leading to
      mitotic arrest has attracted more interest in Eg5 as a potential anticancer drug
      target. We have used hydrogen-deuterium exchange mass spectrometry and directed
      mutagenesis to identify the secondary structure elements that form the binding
      sites of new Eg5 inhibitors, in particular for S-trityl-l-cysteine, a potent
      inhibitor of Eg5 activity in vitro and in cell-based assays. The binding of this
      inhibitor modifies the deuterium incorporation rate of eight peptides that define
      two areas within the motor domain: Tyr125-Glu145 and Ile202-Leu227. Replacement
      of the Tyr125-Glu145 region with the equivalent region in the Neurospora crassa
      conventional kinesin heavy chain prevents the inhibition of the Eg5 ATPase
      activity by S-trityl-l-cysteine. We show here that S-trityl-l-cysteine and
      monastrol both bind to the same region on Eg5 by induced fit in a pocket formed
      by helix alpha3-strand beta5 and loop L5-helix alpha2, and both inhibitors
      trigger similar local conformational changes within the interaction site. It is
      likely that S-trityl-l-cysteine and monastrol inhibit HsEg5 by a similar
      mechanism. The common inhibitor binding region appears to represent a "hot spot"
      for HsEg5 that could be exploited for further inhibitor screening.

PMID- 15476402
TI  - Normal-mode analysis suggests protein flexibility modulation throughout RNA
      polymerase's functional cycle.
AB  - To explore the domain-scale flexibility of bacterial RNA polymerase (RNAP)
      throughout its functional cycle, block normal-mode analyses (BNM) were performed
      on several important functional states, including the holoenzyme, the core
      complex, a model of RNAP bound to primarily duplex DNA, and a model of the
      ternary elongation complex. The calculations utilized a molecular mechanics (MM)
      force field with physical interactions; this is made possible by the use of BNM
      and the implementation of a sparse-matrix diagonalization routine. The use of
      homology models necessitated the MM force field rather than the simpler elastic
      network model (ENM). From the MM/BNM, we have systematically and
      semiquantitatively calculated the atomic fluctuations in the four functional
      states without bias due to crystal packing or other artifactual forces. We have
      observed that both alpha subunits and the omega subunit are rigid, in line with
      their roles as structural motifs that are not mechanistically involved in RNAP's
      functional cycle. It has been observed that the beta subunit has two highly
      mobile domains; these are commonly known as the beta1 and beta2 domains. Our
      calculations suggest that the flexibility of these domains is modulated
      throughout the functional cycle and that they move entirely independently of each
      other unless DNA is bound. From an energetic perspective, we have shown the beta2
      domain can flex into and out of the cleft, forming interactions with DNA in the
      TEC as has been previously proposed. Our calculations also confirm that the beta'
      subunit's likely flexibility into and out of the DNA binding cleft is
      energetically allowed. These two observations validate that both of the RNAP crab
      claw's pincers are mobile, as both beta and beta' have substantial flexibility.

PMID- 15476403
TI  - Identification by phage display selection of a short peptide able to inhibit only
      the strand transfer reaction catalyzed by human immunodeficiency virus type 1
      integrase.
AB  - Human immunodeficiency virus type 1 integrase catalyzes the integration of
      proviral DNA into the infected cell genome, so it is an important potential
      target for antiviral drug design. In an attempt to search for peptides that
      specifically interact with integrase (IN) and inhibit its function, we used an in
      vitro selection procedure, the phage display technique. A phage display library
      of random heptapeptides was used to screen for potential peptide ligands of HIV-1
      IN. Several phage clones were identified that specifically bound IN. Two of the
      selected peptides (FHNHGKQ and HLEHLLF) exhibited a high affinity for IN and were
      chemically synthesized. High affinity was confirmed by a displacement assay which
      showed that these two synthetic peptides were able to compete with the phages
      expressing the corresponding peptide. These agents were assayed on the in vitro
      IN activities. While none of them inhibited the 3'-processing reaction, the
      FHNHGKQ peptide was found to be an inhibitor of the strand transfer reaction.
      Despite its high affinity for IN, the HLEHLLF peptide selected and assayed under
      the same conditions was unable to inhibit this reaction. We showed that the
      FHNHGKQ peptide inhibits specifically the strand transfer activity by competing
      with the target DNA for binding to IN. These IN-binding agents could be used as a
      base for developing new anti-integrase compounds as well as for structural
      studies of the still unknown three-dimensional structure of the entire integrase
      molecule.

PMID- 15476404
TI  - Human carbonyl reductase catalyzes reduction of 4-oxonon-2-enal.
AB  - 4-Oxonon-2-enal (4ONE) was demonstrated to be a product of lipid peroxidation,
      and previous studies found that it was highly reactive toward DNA and protein.
      The present study sought to determine whether carbonyl reductase (CR) catalyzes
      reduction of 4ONE, representing a potential pathway for metabolism of the lipid
      peroxidation product. Recombinant CR was cloned from a human liver cDNA library,
      expressed in Escherichia coli, and purified by metal chelate chromatography. Both
      4ONE and its glutathione conjugate were found to be substrates for CR, and
      kinetic parameters were calculated. TLC analysis of reaction products revealed
      the presence of three compounds, two of which were identified as 4-hydroxynon-2
      enal (4HNE) and 1-hydroxynon-2-en-4-one (1HNO). GC/MS analysis confirmed 4HNE and
      1HNO and identified the unknown reaction product as 4-oxononanal (4ONA). Analysis
      of oxime derivatives of the reaction products via LC/MS confirmed the unknown as
      4ONA. The time course for CR-mediated, NADPH-dependent 4ONE reduction and
      appearance of 4HNE and 1HNO was determined using HPLC, demonstrating 4HNE to be a
      major product and 1HNO and 4ONA to be minor products. Simulated structures of
      4ONE in the active site of CR/NADPH calculated via docking experiments predict
      the ketone positioned as primary hydride acceptor. Results of the present study
      demonstrate that 4ONE is a substrate for CR/NADPH and the enzyme may represent a
      pathway for biotransformation of the lipid. Furthermore, these findings reveal
      that CR catalyzes hydride transfer selectively to the ketone but also to the
      aldehyde and C=C of 4ONE, resulting in 4HNE, 1HNO, and 4ONA, respectively.

PMID- 15476406
TI  - Effects of virion and salt concentrations on the Raman signatures of filamentous
      phages fd, Pf1, Pf3, and PH75.
AB  - Filamentous phages consist of a single-stranded DNA genome encapsidated by
      several thousand copies of a small alpha-helical coat protein subunit plus
      several copies of four minor proteins at the filament ends. The filamentous
      phages are important as cloning vectors, vehicles for peptide display, and
      substrates for macromolecular alignment. Effective use of a filamentous phage in
      such applications requires an understanding of experimental factors that may
      influence the propensity of viral filaments to laterally aggregate in solution.
      Because the Raman spectrum of a filamentous phage is strongly dependent on the
      relative orientation of the virion with respect to the polarization direction of
      the electromagnetic radiation employed to excite the spectrum, we have applied
      Raman spectroscopy to investigate lateral aggregation of phages fd, Pf1, Pf3, and
      PH75 in solution. The results show that lateral aggregation of the virions and
      anisotropic orientation of the aggregates are both disfavored by high
      concentrations of salt (>200 mM NaCl) in solutions containing a relatively low
      virion concentration (<10 mg/mL). Conversely, the formation of lateral aggregates
      and their anisotropic orientation are strongly favored by a low salt
      concentration (<0.1 mM NaCl), irrespective of the virion concentration over a
      wide range. The use of Raman polarization effects to distinguish isotropic and
      anisotropic solutions of filamentous phages is consistent with previously
      reported Raman analyses of virion structures in both solutions and fibers. The
      Raman data are supported by electron micrographs of negatively stained specimens
      of phage fd, which permit an independent assessment of salt effects on lateral
      aggregation. The present results also identify new Raman bands that serve as
      potential markers of subunit side-chain orientations in filamentous virus
      assemblies.

PMID- 15476405
TI  - Asymmetric ATP binding and hydrolysis activity of the Thermus aquaticus MutS
      dimer is key to modulation of its interactions with mismatched DNA.
AB  - Prokaryotic MutS and eukaryotic Msh proteins recognize base pair mismatches and
      insertions or deletions in DNA and initiate mismatch repair. These proteins
      function as dimers (and perhaps higher order oligomers) and possess an ATPase
      activity that is essential for DNA repair. Previous studies of Escherichia coli
      MutS and eukaryotic Msh2-Msh6 proteins have revealed asymmetry within the dimer
      with respect to both DNA binding and ATPase activities. We have found the Thermus
      aquaticus MutS protein amenable to detailed investigation of the nature and role
      of this asymmetry. Here, we show that (a) in a MutS dimer one subunit (S1) binds
      nucleotide with high affinity and the other (S2) with 10-fold weaker affinity,
      (b) S1 hydrolyzes ATP rapidly while S2 hydrolyzes ATP at a 30-50-fold slower
      rate, (c) mismatched DNA binding to MutS inhibits ATP hydrolysis at S1 but slow
      hydrolysis continues at S2, and (d) interaction between mismatched DNA and MutS
      is weakened when both subunits are occupied by ATP but remains stable when S1 is
      occupied by ATP and S2 by ADP. These results reveal key MutS species in the
      ATPase pathway; S1(ADP)-S2(ATP) is formed preferentially in the absence of DNA or
      in the presence of fully matched DNA, while S1(ATP)-S2(ATP) and S1(ATP)-S2(ADP)
      are formed preferentially in the presence of mismatched DNA. These MutS species
      exhibit differences in interaction with mismatched DNA that are likely important
      for the mechanism of MutS action in DNA repair.

PMID- 15476407
TI  - Redox function of tetrahydrobiopterin and effect of L-arginine on oxygen binding
      in endothelial nitric oxide synthase.
AB  - Tetrahydrobiopterin (BH(4)), not dihydrobiopterin or biopterin, is a critical
      element required for NO formation by nitric oxide synthase (NOS). To elucidate
      how BH(4) affects eNOS activity, we have investigated BH(4) redox functions in
      the endothelial NOS (eNOS). Redox-state changes of BH(4) in eNOS were examined by
      chemical quench/HPLC analysis during the autoinactivation of eNOS using
      oxyhemoglobin oxidation assay for NO formation at room temperature. Loss of NO
      formation activity linearly correlated with BH(4) oxidation, and was recovered by
      overnight incubation with fresh BH(4). Thus, thiol reagents commonly added to NOS
      enzyme preparations, such as dithiothreitol and beta-mercaptoethanol, probably
      preserve enzyme activity by preventing BH(4) oxidation. It has been shown that
      conversion of L-arginine to N-hydroxy-L-arginine in the first step of NOS
      catalysis requires two reducing equivalents. The first electron that reduces
      ferric to the ferrous heme is derived from flavin oxidation. The issue of whether
      BH(4) supplies the second reducing equivalent in the monooxygenation of eNOS was
      investigated by rapid-scan stopped-flow and rapid-freeze-quench EPR kinetic
      measurements. In the presence of L-arginine, oxygen binding kinetics to ferrous
      eNOS or to the ferrous eNOS oxygenase domain (eNOS(ox)) followed a sequential
      mechanism: Fe(II) <--> Fe(II)O(2) --> Fe(III) + O(2)(-). Without L-arginine,
      little accumulation of the Fe(II)O(2) intermediate occurred and essentially a
      direct optical transition from the Fe(II) form to the Fe(III) form was observed.
      Stabilization of the Fe(II)O(2) intermediate by L-arginine has been established
      convincingly. On the other hand, BH(4) did not have significant effects on the
      oxygen binding and decay of the oxyferrous intermediate of the eNOS or eNOS
      oxygenase domain. Rapid-freeze-quench EPR kinetic measurements in the presence of
      L-arginine showed a direct correlation between BH(4) radical formation and decay
      of the Fe(II)O(2) intermediate, indicating that BH(4) indeed supplies the second
      electron for L-arginine monooxygenation in eNOS.

PMID- 15476408
TI  - Functional evaluation of heme vinyl groups in myoglobin with symmetric protoheme
      isomers.
AB  - We replaced protoheme-IX in native myoglobin with the symmetric protohemes-III
      and -XIII, in order to investigate the role of heme vinyl-globin contacts on Mb
      function. The UV-visible spectra and the resonance Raman spectra in the high
      frequency region (containing oxidation, spin, and coordination state marker
      lines) of the two reconstituted Mbs were very similar. However, the signal
      intensity of the Soret band in the CD spectra and the resonance Raman lines for
      vinyl bending modes in the low-frequency region notably differed, thereby
      reflecting altered heme peripheral contacts. The redox potentials, formal
      heterogeneous electron-transfer rates, and thermal denaturation temperatures of
      the two reconstituted Mbs were also indistinguishable. In addition, the oxygen
      binding properties of the ferrous deoxy Mbs were comparable. These results
      demonstrate that altered heme vinyl-globin interactions only slightly affect the
      physical properties of Mb. It is therefore likely that the orientation of
      protoheme-IX about the alpha,gamma-axis in the heme pocket is not necessarily a
      crucial factor for oxygen binding to native Mb.

PMID- 15476409
TI  - Conformation and lipid binding of the N-terminal (1-44) domain of human
      apolipoprotein A-I.
AB  - Because of its role in reverse cholesterol transport, human apolipoprotein A-I is
      the most widely studied exchangeable apolipoprotein. Residues 1-43 of human apoA
      I, encoded by exon 3 of the gene, are highly conserved and less well understood
      than residues 44-243, encoded by exon 4. In contrast to residues 44-243, residues
      1-43 do not contain the 22 amino acid tandem repeats thought to form lipid
      binding amphipathic helices. To understand the structural and functional roles of
      the N-terminal region, we studied a synthetic peptide representing the first 44
      residues of human apoA-I ([1-44]apoA-I). Far-ultraviolet circular dichroism
      spectra showed that [1-44]apoA-I is unfolded in aqueous solution. However, in the
      presence of n-octyl beta-d-glucopyranoside, a nonionic lipid mimicking detergent,
      above its critical micelle concentration ( approximately 0.7% at 25 degrees C),
      sodium dodecyl sulfate, an ionic detergent, above its CMC ( approximately 0.2%),
      trimethylamine N-oxide, a folding inducing organic osmolyte, or trifluoroethanol,
      an alpha-helix inducer, alpha-helical structure was formed in [1-44]apoA-I up to
      approximately 45%. Characterization by density gradient ultracentrifugation and
      visualization by negative staining electron microscopy demonstrated that [1
      44]apoA-I interacts with dimyristoylphosphatidylcholine (DMPC) over a wide range
      of lipid:peptide ratios from 1:1 to 12:1 (w/w). At 1:1 DMPC:[1-44]apoA-I (w/w)
      ratio, discoidal complexes with composition approximately 4:1 (w/w) and
      approximately 100 A diameter were formed in equilibrium with free peptide. At
      higher ratios, discoidal complexes were shown to exist together with a
      heterogeneous population of lipid vesicles with peptide bound also in equilibrium
      with free peptide. When bound to DMPC, [1-44]apoA-I has approximately 60% helical
      structure, independent of whether it forms discoidal or vesicular complexes. This
      helical content is consistent with that of the predicted G helix (residues 8-33).
      Our data provide the first strong and direct evidence that the N-terminal region
      of apoA-I binds lipid and can form discoidal structures and a heterogeneous
      population of vesicles. In doing so, approximately 60% of this region folds into
      alpha-helix from random coil. The composition of the 100 A discoidal complex is
      approximately 5 [1-44]apoA-I and approximately 150 DMPC molecules per disk. The
      helix length of 5 [1-44]apoA-I molecules in lipid-bound form is just long enough
      to wrap around the DMPC bilayer disk once.

PMID- 15476410
TI  - Regulation of PutA-membrane associations by flavin adenine dinucleotide
      reduction.
AB  - Proline utilization A (PutA) from Escherichia coli is a multifunctional
      flavoprotein that is both a transcriptional repressor of the proline utilization
      (put) genes and a membrane-associated enzyme which catalyzes the 4-electron
      oxidation of proline to glutamate. Previously, proline was shown to induce PutA
      membrane binding and alter the intracellular location and function of PutA. To
      distinguish the roles of substrate binding and FAD reduction in the mechanism of
      how PutA changes from a DNA-binding protein to a membrane-bound enzyme, the
      kinetic parameters of PutA-membrane binding were measured under different
      conditions using model lipid bilayers and surface plasmon resonance (SPR). The
      effects of proline, FAD reduction, and proline analogues on PutA-membrane
      associations were determined. Oxidized PutA shows no binding to E. coli polar
      lipid vesicles. In contrast, proline and sodium dithionite induce tight binding
      of PutA to the lipid bilayer with indistinguishable kinetic parameters and an
      estimated dissociation constant (K(D)) of <0.01 nM (pH 7.4) for the reduced PutA
      lipid complex. Proline analogues such as L-THFA and DL-P5C also stimulate PutA
      binding to E. coli polar lipid vesicles with K(D) values ranging from
      approximately 3.6 to 34 nM (pH 7.4) for the PutA-lipid complex. The greater PutA
      membrane binding affinity (>300-fold) generated by FAD reduction relative to the
      nonreducing ligands demonstrates that FAD reduction controls PutA-membrane
      associations. On the basis of SPR kinetic analysis with differently charged lipid
      bilayers, the driving force for PutA-membrane binding is primarily hydrophobic.
      In the SPR experiments membrane-bound PutA did not bind put control DNA,
      confirming that the membrane-binding and DNA-binding activities of PutA are
      mutually exclusive. A model for the regulation of PutA is described in which the
      overall translocation of PutA from the cytoplasm to the membrane is driven by FAD
      reduction and the subsequent energy difference ( approximately 24 kJ/mol) between
      PutA-membrane and PutA-DNA binding.

PMID- 15476411
TI  - Coupled sodium/glucose cotransport by SGLT1 requires a negative charge at
      position 454.
AB  - Na(+)/glucose cotransport by SGLT1 is a tightly coupled process that is driven by
      the Na(+) electrochemical gradient across the plasma membrane. We have previously
      proposed that SGLT1 contains separate Na(+)- and glucose-binding domains, that
      A166 (in the Na(+) domain) is close to D454 (in the sugar domain), and that
      interactions between these residues influence sugar specificity and transport. We
      have now expressed the mutant D454C in Xenopus laevis oocytes and examined the
      role of charge on residue 454 by replacing the Asp with Cys or His, and by
      chemical mutation of D454C with alkylating reagents of different charge (MTSES(
      ), MTSET(+), MMTS(0), MTSHE(0), and iodoacetate(-)). Functional properties were
      examined by measuring sugar transport and cotransporter currents. In addition,
      D454C was labeled with fluorescent dyes and the fluorescence of the labeled
      transporter was recorded as a function of voltage and ligand concentration. The
      data shows that (1) aspartate 454 is critically important for the normal
      trafficking of the protein to the plasma membrane; (2) there were marked changes
      in the functional properties of D454C, i.e., a reduction in turnover number and a
      loss of voltage sensitivity, although there were no alterations in sugar
      selectivity or sugar and Na(+) affinity; (3) a negative charge on residue 454
      increased Na(+) and sugar transport with a normal stoichiometry of 2 Na(+):1
      sugar. A positive charge on residue 454, in contrast, uncoupled Na(+) and sugar
      transport, indicating the importance of the negative charge in the coordination
      of the cotransport mechanism.

PMID- 15476413
TI  - Identification of ligand binding regions of the Saccharomyces cerevisiae alpha
      factor pheromone receptor by photoaffinity cross-linking.
AB  - Analogues of alpha-factor, Saccharomyces cerevisiae tridecapeptide mating
      pheromone (H-Trp-His-Trp-Leu-Gln-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr-OH), containing
      p-benzoylphenylalanine (Bpa), a photoactivatable group, and biotin as a tag, were
      synthesized using solid-phase methodologies on a p-benzyloxybenzyl alcohol
      polystyrene resin. Bpa was inserted at positions 1, 3, 5, 8, and 13 of alpha
      factor to generate a set of cross-linkable analogues spanning the pheromone. The
      biological activity (growth arrest assay) and binding affinities of all analogues
      for the alpha-factor receptor (Ste2p) were determined. Two of the analogues that
      were tested, Bpa(1) and Bpa(5), showed 3-4-fold lower affinity than the alpha
      factor, whereas Bpa(3) and Bpa(13) had 7-12-fold lower affinities. Bpa(8)
      competed poorly with [(3)H]-alpha-factor for Ste2p. All of the analogues tested
      except Bpa(8) had detectable halos in the growth arrest assay, indicating that
      these analogues are alpha-factor agonists. Cross-linking studies demonstrated
      that [Bpa(1)]-alpha-factor, [Bpa(3)]-alpha-factor, [Bpa(5)]-alpha-factor, and
      [Bpa(13)]-alpha-factor were cross-linked to Ste2p; the biotin tag on the
      pheromone was detected by a NeutrAvidin-HRP conjugate on Western blots. Digestion
      of Bpa(1), Bpa(3), and Bpa(13) cross-linked receptors with chemical and enzymatic
      reagents suggested that the N-terminus of the pheromone interacts with a binding
      domain consisting of residues from the extracellular ends of TM5-TM7 and portions
      of EL2 and EL3 close to these TMs and that there is a direct interaction between
      the position 13 side chain and a region of Ste2p (F55-R58) at the extracellular
      end of TM1. The results further define the sites of interaction between Ste2p and
      the alpha-factor, allowing refinement of a model for the pheromone bound to its
      receptor.

PMID- 15476414
TI  - Single amino acid mutations interchange the reaction specificities of
      cyclodextrin glycosyltransferase and the acarbose-modifying enzyme acarviosyl
      transferase.
AB  - Acarviosyl transferase (ATase) from Actinoplanes sp. SE50/110 is a bacterial
      enzyme that transfers the acarviosyl moiety of the diabetic drug acarbose to
      sugar acceptors. The enzyme exhibits 42% sequence identity with cyclodextrin
      glycosyltransferases (CGTase), and both enzymes are members of the alpha-amylase
      family, a large clan of enzymes acting on starch and related compounds. ATase is
      virtually inactive on starch, however. In contrast, ATase is the only known
      enzyme to efficiently use acarbose as substrate (2 micromol min(-1) mg(-1));
      acarbose is a strong inhibitor of CGTase and of most other alpha-amylase family
      enzymes. This distinct reaction specificity makes ATase an interesting enzyme to
      investigate the variation in reaction specificity of alpha-amylase family
      enzymes. Here we show that a G140H mutation in ATase, introducing the typical His
      of the conserved sequence region I of the alpha-amylase family, changed ATase
      into an enzyme with 4-alpha-glucanotransferase activity (3.4 micromol min(-1) mg(
      1)). Moreover, this mutation introduced cyclodextrin-forming activity into ATase,
      converting 2% of starch into cyclodextrins. The opposite experiment, removing
      this typical His side chain in CGTase (H140A), introduced acarviosyl transferase
      activity in CGTase (0.25 micromol min(-1) mg(-1)).

PMID- 15476412
TI  - Demonstration of a specific Escherichia coli SecY-signal peptide interaction.
AB  - Protein translocation in Escherichia coli is initiated by the interaction of a
      preprotein with the membrane translocase composed of a motor protein, SecA
      ATPase, and a membrane-embedded channel, the SecYEG complex. The extent to which
      the signal peptide region of the preprotein plays a role in SecYEG interactions
      is unclear, in part because studies in this area typically employ the entire
      preprotein. Using a synthetic signal peptide harboring a photoaffinity label in
      its hydrophobic core, we examined this interaction with SecYEG in a detergent
      micellar environment. The signal peptide was found to specifically bind SecY in a
      saturable manner and at levels comparable to those that stimulate SecA ATPase
      activity. Chemical and proteolytic cleavage of cross-linked SecY and analysis of
      the signal peptide adducts indicate that the binding was primarily to regions of
      the protein containing transmembrane domains seven and two. The signal peptide
      SecY interaction was affected by the presence of SecA and nucleotides in a manner
      consistent with the transfer of signal peptide to SecY upon nucleotide hydrolysis
      at SecA.

PMID- 15476415
TI  - High-affinity metal-binding site in beef heart mitochondrial F1ATPase: an EPR
      spectroscopy study.
AB  - The high-affinity metal-binding site of isolated F(1)-ATPase from beef heart
      mitochondria was studied by high-field (HF) continuous wave electron paramagnetic
      resonance (CW-EPR) and pulsed EPR spectroscopy, using Mn(II) as a paramagnetic
      probe. The protein F(1) was fully depleted of endogenous Mg(II) and nucleotides
      [stripped F(1) or MF1(0,0)] and loaded with stoichiometric Mn(II) and
      stoichiometric or excess amounts of ADP or adenosine 5'-(beta,gamma-imido)
      triphosphate (AMPPNP). Mn(II) and nucleotides were added to MF1(0,0) either
      subsequently or together as preformed complexes. Metal-ADP inhibition kinetics
      analysis was performed showing that in all samples Mn(II) enters one catalytic
      site on a beta subunit. From the HF-EPR spectra, the zero-field splitting (ZFS)
      parameters of the various samples were obtained, showing that different metal
      protein coordination symmetry is induced depending on the metal nucleotide
      addition order and the protein/metal/nucleotide molar ratios. The electron spin
      echo envelope modulation (ESEEM) technique was used to obtain information on the
      interaction between Mn(II) and the (31)P nuclei of the metal-coordinated
      nucleotide. In the case of samples containing ADP, the measured (31)P hyperfine
      couplings clearly indicated coordination changes related to the metal nucleotide
      addition order and the protein/metal/nucleotide ratios. On the contrary, the
      samples with AMPPNP showed very similar ESEEM patterns, despite the remarkable
      differences present among their HF-EPR spectra. This fact has been attributed to
      changes in the metal-site coordination symmetry because of ligands not involving
      phosphate groups. The kinetic data showed that the divalent metal always induces
      in the catalytic site the high-affinity conformation, while EPR experiments in
      frozen solutions supported the occurrence of different precatalytic states when
      the metal and ADP are added to the protein sequentially or together as a
      preformed complex. The different states evolve to the same conformation, the
      metal(II)-ADP inhibited form, upon induction of the trisite catalytic activity.
      All our spectroscopic and kinetic data point to the active role of the divalent
      cation in creating a competent catalytic site upon binding to MF1, in accordance
      with previous evidence obtained for Escherichia coli and chloroplast F(1).

PMID- 15476416
TI  - A single amino acid replacement results in the Ca2+-induced self-assembly of a
      helical conantokin-based peptide.
AB  - Conantokins are short (17-27 amino acid residues), gamma-carboxyglutamate (Gla)
      rich peptide components of the venoms of marine snails of the genus Conus. They
      display high apo and/or Ca(2+)-induced helicity and act as potent and selective
      inhibitors of the N-methyl-d-aspartate receptor (NMDAR). We have previously
      established that one of the conantokins, conantokin-G (con-G), self-associates in
      the presence of Ca(2+) with high specificity for antiparallel chain orientation
      [Dai, Q., Prorok, M., and Castellino, F. J. (2004) J. Mol. Biol. 336, 731-744].
      The dimerization appears to be driven by interhelical Ca(2+) coordination between
      the following residue pairings: Gla(3)-Gla(14)('), Gla(7)-Gla(10)('), Gla(10)
      Gla(7)('), and Gla(14)-Gla(3)('). A second member of the conantokin family,
      conantokin-T (con-T), shares sequence identity with con-G at 8 of 21 amino acids,
      including 4 Gla residues. These similarities notwithstanding, several primary and
      secondary structural differences exist between con-T and con-G. Particularly
      notable is that con-T contains a Lys, rather than a Gla, at position 7. Moreover,
      unlike con-G, con-T does not undergo Ca(2+)-triggered self-assembly. In the
      present study, sedimentation equilibrium ultracentrifugation is employed to
      demonstrate that a single amino acid replacement analogue of con-T, con
      T[K7gamma], assumes a dimeric superstructure in the presence of Ca(2+) at pH
      values consistent with the ionization of Gla carboxylate groups. Furthermore,
      HPLC-monitored thiol-disulfide folding and rearrangement assays with Cys
      containing con-T variants suggest that the relative chain alignment preference in
      the noncovalent complex is antiparallel. Our results suggest that interchain
      Ca(2+) coordination in con-T[K7gamma] is incumbent upon an "i, i + 4, i +7, i
      +11" arrangement of Gla residues, as occurs in native con-G.

PMID- 15476417
TI  - [The diabetic foot].

PMID- 15476418
TI  - [Impact of a clinical pathway for the diabetic foot in a general hospital].
AB  - OBJECTIVE: The ulcers, infections and isquemia of the foot are the main causes of
      hospitalisation of the diabetic patient and, very frequently, they are reason for
      the amputation of the limb. The objective of this investigation consists of
      evaluating the results of a multidisciplinary clinical pathway designed by the
      set of specialists of different departments from our hospital, as well as of the
      associated personnel of infirmary, implied in the management of this pathology.
      PATIENTS AND METHODS: We have analysed the evolution of a series of clinical and
      socio-economic indicators comparing, in the patients admitted with diagnose of
      complicated diabetic foot, the previous period to the implantation of the
      clinical pathway years 1998, 1999 and 2000) with the later period to this
      implantation (years 2001 and 2002). It is evaluated in each group: the percentage
      of greater and smaller amputations, mortality, the average stay, the percentage
      of readmitances in 30 days, the percentage of arteriographies, the percentage of
      patients controlled by rehabilitation, and the economic cost of the individual
      processes, as well as the global cost. In the group including in the clinical
      pathway it was carried out, in addition, a satisfaction survey. The statistical
      comparison was made by means of the Chi square test. RESULTS: We did not find
      differences as far as the average stay, nor to intrahospitable mortality. If we
      found a clear increase in the percentage of arteriographies (of the 3.5% passage
      to 13%), and in the percentage of patients controlled by rehabilitation (of the
      19.8% passage to the 84.3%). The rate of greater amputations of the patients not
      including in the clinical pathway change from 17.4% to 9.7% after the
      implantation of this route. The rate of readmitances to 30 days diminished from
      9.3 to 6,5%. The global economic cost and the average cost by patient have been
      inferior after the implantation of the clinical route. The survey of satisfaction
      of this last group offered a global satisfaction of 95%. CONCLUSIONS: The results
      suggest that the approach to the diagnose and treatment on the complicated
      diabetic foot by means of this multidisciplinary clinical pathway improves the
      evolution of the hospitalised patient, diminishing the number of greater
      amputations, without extending the average stay and maintaining, or even
      diminishing, the global economic cost.

PMID- 15476419
TI  - [Anaerobic bacteriemias: clinical and epidemiological characteristics of
      anaerobic bacteremias in ten years].
AB  - BACKGROUND: The anaerobic bacteremia incidence is decreasing during the last
      years, and although it carries a high mortality rate there are studies that ask
      about the possibility of avoid anaerobic blood cultures thinking about the
      clinical prediction capacity of them. The objective of this study is the analysis
      of incidence and clinical characteristics of anaerobic bacteremias in two periods
      with 10 years of difference and empiric antibiotic treatment received, and if it
      was changed when microbiological results were received . METHODS: Prospective
      study of anaerobic bacteremias during 1985-86 and 1996-97, at university hospital
      analyzing clinical characteristics, incidence, analysis, evolution and empiric
      antibiotic treatment received. The statistical analysis was performed with the
      chi square test or exact Fisher test with statistical significance with p<0.05,
      talking about variables with p<0.10. RESULTS: The incidence of anaerobic
      bacteremias was higher in 1996-97 with 24 cases (5.08%), that during 1985-86 with
      22 cases (4.24%). The variables with statistical significative differences with
      p<0.10 were: intrahospitalary adquisition (p<0.10); genitourinary and vascular
      manipulation (p=0.02 and p=0.06), and hypotension (p=0.034) more frequent during
      the first period than during the second one. There isn t statistical difference
      in evolution to cure although the percentage was higher during the second period
      (62.5%), that during the first one (54.6%), being the empiric treatment very high
      in both periods. Bacteroides fragilis was the most frequent microorganism and
      abdominal origin the most frequent one in both periods. CONCLUSION: Although
      there is a low anaerobic bacteremia incidence this one hasn't diminished in ten
      years. Anaerobic bacteremias have a high mortality index although the most part
      of empirical antibiotic treatments are correct. It could ask about the
      possibility of avoid anaerobic blood cultures or ask about them only in clinic
      suspicion of them.

PMID- 15476420
TI  - [Outcome at year after rehabilitation of proximal femur fracture in older than 84
      years].
AB  - OBJECTIVE: To evaluate rehabilitation outcomes at discharge and at year patients
      older 85 years admitted to functional treatment after hip fracture. METHOD: A
      prospective study of inpatients admitted after hip fracture to medium-stay
      geriatric unit between May 2000 and September 2002. Baseline, clinical variables
      (location of fracture, serum albumin and Charlson comorbidity index), functional
      status assessed by Barthel Index, mobility by Physical Red Cross Scale and
      cognitive status by Pfeiffer questionnaire. Functional status, mobility,
      institutionalization and death was evaluated at discharge and by phone interview
      at years after discharge. RESULTS: 116 patients were studied (42% with 85 years
      and older, 85% women). After multivariable logistic analysis, age older than 84
      years did not appear as a factor related to functional dependence or
      institutionalization at discharge or one year after. Indeed, oldest old age was
      not related with death or institutionalization and mobility dependence one year
      after. In the other hand, the presence of cognitive impairment at admission and
      functional impairment before hip fracture were independently variable associated
      to the presence of poor outcome at discharge and one year after. CONCLUSIONS:
      Oldest old age does not appear as a independent risk factor of poor outcomes
      after rehabilitation of hip fracture when other related clinical, functional and
      mental factors are considered.

PMID- 15476421
TI  - [Tuberculosis and cancer. Experience of a general hospital].
AB  - Tuberculosis and cancer are two processes in relationship. The relation between
      both are studied. We analyzed retrospectively the culture-positive tuberculosis
      cases in from 1999 to 2002. We described the six cases with tuberculosis and
      cancer. One hundred and five cases of tuberculosis were observed, 6 cases (5.7%)
      had cancer. Four cases were pulmonary tuberculosis, one tuberculous pleurisy and
      other urinary tuberculosis urinary. The two cases with bronchogenic neoplasm had
      a diagnosis of tuberculosis at same time than cancer. The diagnosis of neoplasm
      was previous than tuberculosis in two cases (breast neoplasm and hypernephroma),
      and posterior in others two cases (breast and colon neoplasm). Half of theses
      patients died. In patients with neoplasm, the possibility of coexist tuberculosis
      is not depreciable, previous, concomitant or after the diagnosis of neoplasm.

PMID- 15476422
TI  - [Tuberculosis of ankle].
AB  - The authors present a case of tuberculous arthritis of ankle with sinovial fluid
      and sputum aspirate Lowenstein positive (M. tuberculosis) in a patient non
      inmunocomprometid and review the clinical, diagnosis and treatment aspects of
      this entity, and show the difficult diagnosis in cases of radiology normal or low
      suspect.

PMID- 15476423
TI  - [Eosinophilic gastroenteritis: two cases report].
AB  - Eosinophilic gastroenteritis is a rare condition characterized by eosinophilic
      infiltration or the different layers of the intestinal wall. Clinical symptoms
      depend of the site of eosinophilic infiltration and the layers involved. Usually
      characterized by peripheral eosinophilia. Definitive diagnosis is based on
      histopathological findings. We report two cases with excellent response to
      steroid therapy.

PMID- 15476424
TI  - [Painful neuropathy in the diabetic foot syndrome: a review].
AB  - Diabetes mellitus (DM) is the most common cause of neuropathy in the western
      world. Recent studies estimate prevalence around 28,5% but results vary depending
      on measure used to define diabetic neuropathy. Early detection and careful
      attention to risk factors determining diabetic foot may avoid or delay
      complications. Pain generation is due to biologic causes as well as physical and
      emotional ones. Neuropathy may result in amputation through different ways
      including loss of one or more functions in peripheral nerves. Glycaemic control,
      symptom control and feet care are standard measures that affect all health
      professionals implied in diabetic patients attention. Deeper knowledge of
      pathogenic mechanisms should result in new treatments which seem to be more
      effective if administered early, when abnormalities are more likely to be
      reversible.

PMID- 15476425
TI  - [Training simulators in digestive endoscopy].
AB  - Advanced techniques, optimal patient care, and quality management are currently
      important topics in clinical medicine. The increasing numbers of minimally
      invasive procedures being carried out in gastroenterology and surgery, and the
      effects of the learning curve on complication rates with various procedures, have
      given rise a recently debate on training standards. Public awareness and
      increasing legal pressure to show and document competence have further
      contributed to the importance of training in interventional medicine. Although
      evidence-based medicine is rapidly becoming the gold standard for treatment
      modalities, responsibility for education-including the theoretical background, as
      well as acquiring and refining manual skills in gastrointestinal endoscopy--is
      still a matter for the individual physician. Practical skills are routinely
      acquired by practicing on patients, initially under the supervision of a senior
      endoscopist. The development of new endoscopy simulators has brought out the
      debate whether training in basic manual skills is better obtained outside the
      patient. This paper presents an overview of the training simulators currently
      available and issues associated with them.

PMID- 15476426
TI  - [Prevalence of the metabolic syndrome in the patients infected with human
      immunodeficiency virus].

PMID- 15476427
TI  - [Acute disseminated encephalomyelitis secondary to influenza vaccination].

PMID- 15476428
TI  - [Osteomyelitis of the rib due to Morganella morganii].

PMID- 15476429
TI  - [Subacute polyneuropathy as presentation of sarcoidosis].

PMID- 15476430
TI  - [Lymphocytic colitis induced by carbamazepine].

PMID- 15476431
TI  - [Visceral leishmaniasys in an immunocompetent patient: an entity to be considered
      in the differential diagnosis of fever of unknown origin].

PMID- 15476432
TI  - [Subcutaneous abscess by Mycobacterium avium complex in HIV patient].

PMID- 15476433
TI  - [Hereditary angioedema of delayed onset].

PMID- 15476434
TI  - [Renal angiomyolipoma and tuberous sclerosis complex].

PMID- 15476436
TI  - Cardiac natriuretic peptides for cardiac health.
AB  - The cardiac natriuretic peptides, ANP (atrial natriuretic peptide) and BNP (brain
      natriuretic peptide), are secreted by the heart in proportion to cardiac
      transmural pressures. They possess a wide range of effects in multiple tissues
      facilitating overall pressure/volume homoeostasis. The close relationship between
      plasma concentrations of these peptides and 'cardiac load' has led to their use
      as biomarkers of cardiac health with diagnostic and prognostic applications in a
      variety of disorders affecting the cardiovascular system. BNP and its N-terminal
      fragment (NT-BNP) are especially sensitive indicators of cardiac dysfunction and
      remodelling, and correlate strongly with severity. Given that cardiac ischaemia
      is also an important trigger for the release of these ventricular peptides, they
      may likewise play a role in the detection of coronary artery disease. Measurement
      of BNP/NT-BNP shows particular promise as a 'rule out' test for suspected cases
      of HF (heart failure) in both emergency care and outpatient settings, and may
      assist in identifying individuals with asymptomatic ventricular impairment who
      will benefit from therapy preventing progression to overt HF. The BNP peptides
      also predict subsequent haemodynamic deterioration and adverse events in
      cardiovascular disease, and can therefore be used to monitor those at high risk
      and act as a guide to optimization of treatment. The favourable biological
      properties of the natriuretic peptides have also led to their use as therapeutic
      agents.

PMID- 15476437
TI  - Cardiac autonomic activity and Type II diabetes mellitus.
AB  - CAN (cardiac autonomic neuropathy) is a common complication of diabetes. Meta
      analyses of published data demonstrate that reduced cardiovascular autonomic
      function, as measured by heart rate variability, is strongly associated with an
      increased risk of silent myocardial ischaemia and mortality. A major problem in
      ischaemia-induced impairment of vascular performance in the diabetic heart is
      unrecognized cardiac sympathetic dysfunction. Determining the presence of CAN is
      based on a battery of autonomic function tests and techniques such as SPECT
      (single-photon emission computed tomography) and PET (positron emission
      tomography). Nevertheless, spectral analysis of heart rate variability seems to
      remain the primary technique in evaluating CAN, due to its low cost, easy use and
      good intra-individual reproducibility.

PMID- 15476438
TI  - Effects of androgen substitution on lipid profile in the adult and aging
      hypogonadal male.
AB  - The decrease in serum bioavailable testosterone may be responsible for the
      catabolic sequelae noticed in the aging man (decrease in libido, decrease in
      muscle mass, osteoporosis and increase in adiposity). After a brief review of
      androgen and lipid metabolism as well as their modifications with aging, we
      discuss current knowledge of the effects of androgen substitution on the lipid
      profile in hypogonadal men. The results of studies concerning the effect of
      androgen substitution therapy on lipids are conflicting but might be favorable.
      The small decrease in high-density lipoprotein cholesterol observed when
      administering standard dosages of testosterone is accompanied by a significant
      decrease in total cholesterol (CT) and low-density lipoprotein cholesterol. A
      counterbalancing of these effects plausibly accounts for the absence of increase
      cardiovascular risk. The currently available preparations are oral, injectable or
      transdermal formulations of natural testosterone. The development of new androgen
      preparations that are more potent, metabolically stable and tissue-specific will
      improve therapeutic benefits and reduce side effects.

PMID- 15476439
TI  - Transsexuals and competitive sports.
AB  - Men generally have an inherent performance advantage over women due to their
      average greater height and muscle mass and power, as the result of
      correspondingly different exposures to androgens. Therefore, it is considered
      fair that in sports men and women compete in separate categories. The question
      now emerging is whether reassigned transsexuals can compete in fairness with
      others of their new sex. The pertinent question is how far the previous effects
      of testosterone in male-to-female transsexuals (M-F) are reversible upon androgen
      deprivation so that M-F have no advantage over women, and, vice versa, what the
      effects are of androgen exposure in female-to-male transsexuals (F-M) on
      variables relevant to competition in sports. Before puberty, boys and girls do
      not differ in height, muscle and bone mass. Recent information shows convincingly
      that actual levels of circulating testosterone determine largely muscle mass and
      strength, though with considerable interindividual diversity. This study analyzed
      the effects of androgen deprivation in 19 M-F and of androgen administration to
      17 F-M on muscle mass, hemoglobin (Hb) and insulin-like growth factor-1 (IGF-1).
      Before cross-sex hormone administration, there was a considerable overlap in
      muscle mass between M-F and F-M. In both M-F and F-M, height was a strong
      predictor of muscle mass. Androgen deprivation of M-F decreased muscle mass,
      increasing the overlap with untreated F-M, but mean muscle mass remained
      significantly higher in M-F than in F-M. Androgen administration to F-M increased
      muscle mass without inducing an advantage over nontreated M-F. The conclusion is
      that androgen deprivation in M-F increases the overlap in muscle mass with women
      but does not reverse it, statistically. The question of whether reassigned M-F
      can fairly compete with women depends on what degree of arbitrariness one wishes
      to accept, keeping in mind, for instance, that similar blood testosterone levels
      in men have profoundly different biologic effects on muscle properties, rendering
      competition in sports intrinsically a matter of how nature endows individuals for
      this competition.

PMID- 15476440
TI  - Acromegaly databases--time for European unification.

PMID- 15476441
TI  - A thyroid nodule revealing a paraganglioma in a patient with a new germline
      mutation in the succinate dehydrogenase B gene.
AB  - A 32-year-old asymptomatic female was diagnosed with an isolated thyroid nodule
      of 2.5 cm diameter. Fine needle aspiration suggested a medullary thyroid
      carcinoma. Consequently, a total thyroidectomy was performed. The nodule stained
      positive for chromogranin A, neurone-specific enolase and synaptophysin, but not
      for calcitonin. Finally, pathological analysis showed a thyroid paraganglioma.
      Although the tumour appeared to be sporadic in a patient with no personal or
      familial history of paraganglioma and/or pheochromocytoma, we have identified a
      new mutation (392delC) of the succinate dehydrogenase-B (SDHB) gene in the
      genomic DNA extracted from the leukocytes of the patient. That mutation induced a
      shift in the reading frame of the gene creating a premature stop codon
      (P131fsX135) which was predicted to result in a truncated SDHB protein of 135
      amino acids. This report highlights the difficulties of this unexpected diagnosis
      of hereditary thyroid paraganglioma. It also discusses the clinical involvements
      in terms of familial screening and the necessary follow-up of the patient.

PMID- 15476442
TI  - Epidemiology, clinical characteristics, outcome, morbidity and mortality in
      acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de
      Acromegalia, REA).
AB  - OBJECTIVE: To undertake a multicentre epidemiological study reflecting acromegaly
      in Spain. DESIGN: Voluntary reporting of data on patients with acromegaly to an
      online database, by the managing physician. METHODS: Data on demographics,
      diagnosis, estimated date of initial symptoms and diagnosis, pituitary imaging,
      visual fields, GH and IGF-I concentrations (requested locally), medical,
      radiotherapy and neurosurgical treatments, morbidity and mortality were
      collected. RESULTS: Data were included for 1219 patients (60.8% women) with a
      mean age at diagnosis of 45 years (s.d. 14 years). Reporting was maximal in 1997
      (2.1 cases per million inhabitants (c.p.m.) per year); prevalence was globally 36
      c.p.m., but varied between 15.7 and 75.8 c.p.m. in different regions. Of 1196
      pituitary tumours, most were macroadenomas (73%); 81% of these patients underwent
      surgery, 45% received radiotherapy and 65% were given medical treatment
      (somatostatin analogues in 68.3% and dopamine agonists in 31.4%). Cures (GH
      values (basal or after an oral glucose tolerance test) <2 ng/ml, normal IGF-I, or
      both) were observed in 40.3% after surgery and 28.2% after radiotherapy.
      Hypertension (39.1%), diabetes mellitus (37.6%), hypopituitarism (25.7%), goitre
      (22.4%), carpal tunnel syndrome (18.7%) and sleep apnoea (13.2%) were reported as
      most frequent morbidities; 6.8% of the patients had cancer (breast in 3.1% of the
      women and colon in 1.2% of the cohort). Fifty-six patients died at a mean age of
      60 years (s.d. 14 years), most commonly of a cardiovascular cause (39.4%);
      mortality was greater in patients given radiotherapy (hazard ratio 2.29; 95%
      confidence interval 1.03 to 5.08; P=0.026), and in those in whom GH and IGF-I
      concentrations were never normal (P<0.001). CONCLUSIONS: This acromegaly registry
      offers a realistic overview of the epidemiological characteristics, treatment
      outcome and morbidity of acromegaly in Spain. As active disease and treatment
      with radiotherapy are associated with an increase in mortality, efforts to
      control the disease early are desirable.

PMID- 15476443
TI  - Intravenous administration of ghrelin stimulates growth hormone secretion in
      vagotomized patients as well as normal subjects.
AB  - OBJECTIVE: Ghrelin is a potent peptide stimulating GH secretion. Besides its
      direct action on the pituitary, ghrelin has been reported to stimulate GH release
      via the vagal afferent nerve in rats. To examine the involvement of vagal nerve
      in ghrelin-induced GH secretion in humans, GH responses to ghrelin were compared
      between vagotomized patients with gastrectomy and normal subjects. METHODS:
      Ghrelin (0.2 microg/kg) or GHRH (1 microg/kg) was administered intravenously in
      vagotomized patients and normal subjects on separate days, and plasma GH
      responses to the stimuli were examined. RESULTS: Ghrelin caused a significant
      plasma GH rise in both vagotomized patients and normal subjects. Peak GH levels
      in vagotomized patients (37.5+/-16.9 ng/ml) were not different from those in
      normal subjects (29.9+/-23.1 ng/ml). The areas under the curve of GH response to
      ghrelin did not differ between the two groups. GHRH also increased GH levels, and
      peak GH levels and areas under the curve after GHRH stimulation were also
      comparable between vagotomized patients and normal subjects. CONCLUSIONS: In the
      present study, the involvement of the afferent vagal nerve in ghrelin-induced GH
      secretion was not confirmed in humans.

PMID- 15476444
TI  - Circulating and cerebrospinal fluid ghrelin and leptin: potential role in altered
      body weight in Huntington's disease.
AB  - OBJECTIVE: In addition to neurological impairment, weight loss is a prominent
      characteristic of Huntington's disease (HD). Neuropathologically, the disease
      affects the caudate nucleus and the cerebral cortex, and also the hypothalamus.
      The recently discovered orexigenic hormone of gastric origin, ghrelin and the
      adipocyte hormone leptin, are two peripherally produced hormones exerting
      opposite effects on specific populations of hypothalamic neurons that play a key
      role in regulating energy intake and energy output. The aim of this study was to
      investigate the possible involvement of cerebrospinal fluid (CSF) and circulating
      ghrelin and leptin in the regulation of energy balance in patients with HD.
      METHODS: Twenty healthy normal-weight subjects undergoing orthopedic surgery, and
      fifteen patients with genetically verified HD, were enrolled in this study. The
      unified Huntington's disease rating scale (UHDRS) was used to assess clinical
      course of the disease. Blood samples for hormonal measurements were obtained by
      venipuncture and in-parallel CSF samples for leptin/ghrelin determination were
      obtained by lumbar puncture. RESULTS: Patients with HD had increased
      concentrations of ghrelin in plasma compared with healthy subjects (4523.7+/
      563.9 vs 2781.1+/-306.2 pg/ml, P<0.01). On the other hand, patients with HD had
      decreased concentrations of leptin in plasma compared with healthy subjects
      (4.8+/-1.6 vs 10.9+/-2.4 ng/ml, P<0.01). The concentrations of CSF ghrelin and
      CSF leptin were equivalent to values in healthy subjects. No correlation was
      found between disease duration--and other clinical features of HD--and plasma or
      CSF leptin/ghrelin levels. In patients with HD, baseline levels of GH, IGF-I,
      insulin and glucose did not differ from those in healthy subjects. CONCLUSION:
      High circulating ghrelin and low leptin levels in patients with HD suggest a
      state of negative energy balance. Early nutritional support of patients with HD
      is advocated since patients with HD and higher body mass index at presentation
      have slower progression of the disease.

PMID- 15476445
TI  - Serum adiponectin levels in adults with Prader-Willi syndrome are independent of
      anthropometrical parameters and do not change with GH treatment.
AB  - OBJECTIVE: Obesity and growth hormone (GH) deficiency are common in Prader-Willi
      syndrome (PWS) and these patients are at risk of metabolic diseases in adult life
      and of reduced life span. Low adiponectin values are associated with obesity and
      the metabolic syndrome. We therefore found it of interest to measure adiponectin
      levels in PWS. PATIENTS AND METHODS: 17 adults, nine men and eight women, 17 to
      32 years of age, with a mean body mass index (BMI) of 35+/-3.2 kg/m2
      participated. All had clinical PWS. They were randomized to treatment with
      placebo or GH (Genotropin) for six months, and subsequently all received GH for
      12 months. At baseline, serum total adiponectin levels in the PWS patients were
      compared with 25 lean and 34 obese controls. Body composition and various
      metabolic parameters, including adiponectin, were studied every six months in the
      PWS group. RESULTS: Serum adiponectin levels in PWS subjects were significantly
      lower (P<0.001) compared with lean and significantly higher (P<0.001) compared
      with obese controls. In PWS patients, no correlation was found between
      adiponectin and anthropometrical parameters or measures of insulin sensitivity
      (e.g. fasting insulin and insulin sensitivity as estimated by the homeostasis
      model assessment), or between adiponectin and IGF binding protein-1 or IGF-I.
      Adiponectin did not change during GH intervention. CONCLUSION: In this study of
      adults with PWS serum total adiponectin levels were higher than in controls with
      simple obesity and were independent of anthropometrical parameters. In accordance
      with this the metabolic syndrome is not necessarily present in all PWS patients.
      Correction of GH deficiency had no effect on serum adiponectin levels.

PMID- 15476446
TI  - TPIT mutations are associated with early-onset, but not late-onset isolated ACTH
      deficiency.
AB  - OBJECTIVE: Congenital isolated ACTH deficiency (IAD) is a rare inherited disorder
      that is clinically and genetically heterogeneous. Patients are characterised by
      low or absent cortisol production secondary to low plasma ACTH despite normal
      secretion of other pituitary hormones and the absence of structural pituitary
      defects. Onset may occur in the neonatal period, but may first be observed in
      later childhood. Recently, mutations in the TPIT gene, a T-box factor selectively
      expressed in developing corticotroph cells, have been found in cases of early
      onset IAD. DESIGN: Here we report the screening of the TPIT gene in seven
      patients with IAD, four of whom had neonatal onset. METHODS: Genomic DNA was
      extracted and the sequences of the 8 TPIT exons and their intron/exon junctions
      were determined by automated sequencing. RESULTS: Two siblings with early-onset
      IAD were both compound heterozygotes for mutations in exons 2 and 6. The missense
      mutation (Met86Arg) in exon 2 within the T-box (or DNA binding domain) is
      predicted to disrupt DNA binding. A frameshift mutation in exon 6 (782delA)
      introduces a premature stop codon and is likely to lead to a non-functional
      truncated protein. No nucleotide changes were observed in exonic sequences in the
      other two early- or the three later-onset cases. Fifteen single nucleotide
      polymorphisms that were not predicted to change the TPIT transcript were also
      detected. CONCLUSIONS: These findings provide a further illustration of the
      genetic heterogeneity of IAD and are highly suggestive of one or more other genes
      being implicated in this disorder.

PMID- 15476447
TI  - Serum thyrotropin-receptor autoantibodies levels after I therapy in Graves'
      patients: effect of pretreatment with methimazole evaluated by a prospective,
      randomized study.
AB  - OBJECTIVE: Radioiodine therapy (131I) in hyperthyroid Graves' disease is
      generally followed by a transitory increase in levels of thyrotropin receptors
      antibodies (TRAb). Immunosuppressive effects of antithyroid drugs are still a
      matter of debate. In this study we evaluated the effect of methimazole
      pretreatment on the TRAb boost induced by 131I. DESIGN: A randomized, prospective
      clinical trial. METHODS: 61 patients were randomly assigned to receive 131I alone
      (32 patients) or 131I plus pretreatment with methimazole (30 mg/day; 29
      patients). Serum TRAb levels were measured on the day of 131I dosing (D0), and at
      1, 3, 6 and 12 months after 131I administration. RESULTS: The mean serum TRAb
      levels decreased significantly from baseline to D0 in patients treated with
      methimazole (80.8 vs 48.8 U/l; P<0.05). After 131I treatment, TRAb levels
      increased at 3 months (48.8 to 60 U/l; 19%) and they were still elevated at 6
      months compared with D0 values (99.9 U/l; 105%). Thereafter, TRAb levels
      decreased to baseline values (47.8 U/l) at 12 months. In hyperthyroid patients,
      TRAb levels increased significantly from D0 to 1 month (45.0 to 78 U/l; 73%)
      reaching their highest levels at 3 months (225 U/l; 400%). After this, we
      observed a progressive decrease to the baseline levels at 12 months (40.0 U/l).
      The course of TRAb levels after 131I treatment was significantly different
      between the two groups (P<0.05). Multiple regression analysis identified serum
      TRAb levels on D0 as independent predictors of TRAb increment after 131I therapy
      (r2=0.34; P=0.001). A higher increment in serum TRAb levels was associated with
      hypothyroidism after 1 year of follow-up. CONCLUSION: Methimazole pretreatment
      attenuates the 131I-induced rise in serum TRAb levels. The effects of methimazole
      could be attributed to a direct immunomodulatory action or may be due to its
      effects on the control of hyperthyroidism, which is a known cause of immune
      dysregulation.

PMID- 15476448
TI  - Increased serum soluble leptin receptor levels in children and adolescents with
      type 1 diabetes mellitus.
AB  - OBJECTIVE: We investigated whether or not serum levels of the soluble leptin
      receptor (sOB-R) and leptin are related to anthropometric and metabolic changes
      during pubertal development of children and adolescents with type 1 diabetes
      mellitus. DESIGN AND METHODS: Blood levels of sOB-R, leptin and HbA1C, as well as
      body-mass index (BMI), diabetes duration and daily insulin doses, were determined
      in 212 (97 girls; 115 boys) children with type 1 diabetes mellitus and compared
      with the sOB-R serum levels in 526 healthy children and adolescents. RESULTS: OB
      R serum levels and parallel values of the molar ratio between sOB-R and leptin
      were significantly higher in children with diabetes than in normal children
      (P<0.05) in almost all investigated Tanner stages. Furthermore, in the entire
      group of patients, we demonstrated statistically significant correlations
      (P<0.02) between sOB-R and the duration of diabetes (r=0.30), HbA1c levels
      (r=0.32) and the insulin dose (r=0.18). Multiple-regression analysis revealed
      that HbA1c (12.4%), height (7.9%) and duration of diabetes (8.7%) contributed to
      29% variance of sOB-R in diabetic children. CONCLUSIONS: Our data suggest that
      poor glycemic control in diabetes may lead to increased serum levels of sOB-R.
      This regulation of sOB-R appears to be independent of leptin, but may have an
      impact on leptin action. The consequently developing molar excess of sOB-R
      related to leptin could reduce leptin sensitivity and may, therefore, influence
      leptin-related anthropometric and metabolic abnormalities.

PMID- 15476449
TI  - Insulin resistance and endothelial function are improved after folate and vitamin
      B12 therapy in patients with metabolic syndrome: relationship between
      homocysteine levels and hyperinsulinemia.
AB  - OBJECTIVE: The purpose of this study was (a) to study whether a folate and
      vitamin B12 treatment, aimed at decreasing homocysteine levels, might ameliorate
      insulin resistance and endothelial dysfunction in patients with metabolic
      syndrome according to the National Cholesterol Education Program-Adult Treatment
      Panel-III criteria and (b) to evaluate whether, under these metabolic conditions,
      there is a relationship between hyperhomocysteinemia and insulin resistance.
      DESIGN AND METHODS: A double-blind, parallel, identical placebo-drug, randomized
      study was performed for 2 months in 50 patients. Patients were randomly allocated
      to two groups. In group 1, patients were treated with diet plus placebo for 2
      months. In group 2, patients were treated with diet plus placebo for 1 month,
      followed by diet plus folic acid (5 mg/day) plus vitamin B12 (500 microg/day) for
      another month. RESULTS: In group 2, folate treatment significantly decreased
      homocysteine levels by 27.8% (12.2+/-1.2 vs 8.8+/-0.7 micromol/l; P<0.01). A
      significant decrement was observed for insulin levels (19.9+/-1.7 vs 14.8+/-1.6
      microU/ml; P<0.01) accompanied by a 27% reduction in the homeostasis model
      assessment levels. A positive relationship was found between the decrement of
      homocysteine and insulin levels (r=0.60; P<0.002). In parallel, endothelial
      dysfunction significantly improved in the treated group, since post-ischemic
      maximal hyperemic vasodilation increased by 29.8% and cGMP by 13.6% while
      asymmetrical dimethylarginine levels decreased by 21.7%. On the contrary, in
      group 1 patients, treated with placebo, no changes were shown in any of the
      variables. CONCLUSIONS: Folate and vitamin B12 treatment improved insulin
      resistance and endothelial dysfunction, along with decreasing homocysteine
      levels, in patients with metabolic syndrome, suggesting that folic acid has
      several beneficial effects on cardiovascular disease risk factors.

PMID- 15476450
TI  - Changes in bone density and bone markers in rhythmic gymnasts and ballet dancers:
      implications for puberty and leptin levels.
AB  - OBJECTIVE: Our aim was to compare physical activity and biochemical markers with
      bone mineral acquisition in rhythmic gymnasts and ballet dancers. METHODS:
      Weight, height, body mass index, nutritional intake, bone age and menstrual
      histories were analyzed in nine rhythmic gymnasts, twelve ballet dancers and
      fourteen controls. Bone mineral density (BMD) was assessed by X-ray
      absorptiometry at the lumbar spine, hip and radius. Bone alkaline phosphatase
      (bAP) and amino-terminal propeptide of procollagen I (PNIP) in serum and urinary
      alpha-isomer of the carboxy-terminal telopeptide of collagen I (alpha-CTX) were
      measured. RESULTS: Bone age was delayed 2 years and mean age at menarche was 15+/
      0.9 years in rhythmic gymnasts and 13.7+/-1 years in ballet dancers, compared
      with 12.5+/-1 years in controls. Trocanteric and femoral neck BMD was
      significantly higher in rhythmic gymnasts compared with ballet dancers and
      controls. Right forearm (non-loaded zone) BMD was significantly decreased in
      rhythmic gymnasts and ballet dancers compared with controls. All subjects had
      normal bAP and PNIP levels, but the alpha-CTX/creatinine (Cr) ratio was increased
      in rhythmic gymnasts (P<0.001) with an inverse correlation between right forearm
      BMD and the alpha-CTX/Cr ratio (r=-0.74, P<0.001). Serum leptin levels were
      decreased in rhythmic gymnasts and ballet dancers. Rhythmic gymnasts had a
      positive correlation between right forearm BMD and leptin levels (r=0.85,
      P<0.001). CONCLUSIONS: Decreased bone mass in rhythmic gymnasts could be
      partially explained by an increase in bone resorption. Serum leptin levels could
      be implicated in the pubertal delay and be a good marker of bone mass in these
      subjects.

PMID- 15476451
TI  - Interleukin-18, a proinflammatory cytokine, contributes to the pathogenesis of
      non-thyroidal illness mainly via the central part of the hypothalamus-pituitary
      thyroid axis.
AB  - OBJECTIVE: Proinflammatory cytokines are involved in the pathogenesis of non
      thyroidal illness (NTI), as shown by studies with IL-6-/- and IL-12-/- mice.
      Interleukin (IL)-6 changes peripheral thyroid hormone metabolism, and IL-12 seems
      to be involved in the regulation of the central part of the hypothalamic
      pituitary-thyroid (HPT) axis during illness. IL-18 is a proinflammatory cytokine
      which shares important biological properties with IL-12, such as interferon (IFN)
      gamma-inducing activity. DESIGN: By studying the changes in the HPT-axis during
      bacterial lipopolysaccharide (LPS)-induced illness in IL-18-/-, IFNgammaR-/- and
      wild-type (WT) mice, we wanted to unravel the putative role of IL-18 and IFNgamma
      in the pathogenesis of NTI. RESULTS: LPS induced a decrease in pituitary type 1
      deiodinase (D1) activity (P<0.05, ANOVA) in WT mice, but not in IL-18-/- mice,
      while the decrease in D2 activity was similar in both strains. LPS decreased
      serum thyroid hormone levels and liver D1 mRNA within 24 h similarly in IL-18-/-,
      and WT mice. The expression of IL-1, IL-6 and IFNgamma mRNA expression was
      significantly lower in IL-18-/- mice than in WT, while IL-12 mRNA expression was
      similar. IFNgammaR-/- mice had higher basal D1 activity in the pituitary than WT
      mice (P<0.05); LPS induced a decrease of D2, but not of D1, activity in the
      pituitary which was similar in both strains. In the liver, the LPS-induced
      increase in cytokine expression was not different between IFNgammaR-/- mice and
      WT mice, and the decrease in serum T3 and T4 levels and hepatic D1 mRNA was also
      similar. CONCLUSIONS: The relative decrease in serum T3 and T4 and liver D1 mRNA
      in response to LPS is similar in IL-18-/-, IFNgammaR-/- and WT mice despite
      significant changes in hepatic cytokine induction. However, the LPS-induced
      decrease in D1 activity in the pituitary of WT mice is absent in IL-18-/- mice;
      in contrast, LPS did not decrease pituitary D1 activity in the IFNgammaR-/- mice
      or their WT, which might be due to the genetic background of the mice. Our
      results suggest that IL-18 is also involved in the regulation of the central part
      of the HPT axis during illness.

PMID- 15476452
TI  - Dose-response of estrogen on bone versus the uterus in ovariectomized mice.
AB  - BACKGROUND: Estrogen is known to have important effects on both reproductive and
      non-reproductive tissues. Moreover, there is increasing interest in developing
      compounds that may have selective effects on bone versus reproductive tissues.
      METHODS: Since mouse models are often used in these studies, we administrated
      increasing doses of estradiol (E2) (0 to 500 microg/kg/day) by slow release
      pellets to ovariectomized 6-month-old C57BL/6 mice and assessed skeletal and
      uterine responses following 2 months of treatment. RESULTS: The mice lost bone at
      multiple sites following ovariectomy (OVX); however, while the lowest E2 dose of
      5 microg/kg/day completely prevented loss of cancellous bone (at the lumbar spine
      and tibial metaphysis), it had no stimulatory effects on the uterus. Higher doses
      of E2 resulted in further increases in bone mineral density, with eventual
      stimulation of the uterus at a dose of 40 microg/kg/day. By contrast, when 3
      month-old C57BL/6 mice were administered the same doses of E2 and studied after 1
      month, the 5 microg/kg/day dose resulted in uterine hypertropy, but was not able
      to prevent loss of cancellous bone. CONCLUSIONS: Thus these results (i) provide
      data on the dose-response for the effects of E2 on mouse bone and (ii) indicate
      that the relative effects of E2 on bone versus the uterus are highly dependent on
      the particular experimental conditions used. This issue needs to be considered in
      evaluating agents with potential 'selective' effects on bone versus reproductive
      tissues.

PMID- 15476453
TI  - Regulatory role of BMP2 and BMP7 in spermatogonia and Sertoli cell proliferation
      in the immature mouse.
AB  - AIM: The aim of this study was to determine the action of bone morphogenetic
      proteins (BMPs) on testicular cell proliferation during early postnatal life, a
      definite developmental time at which crucial changes in germ cell and Sertoli
      cell maturation occur. METHODS: We investigated the effect of BMP2 and BMP7, two
      factors which belong to the relatively distant decapentaplegic (DPP) and 60 A
      classes of the large BMP family, upon spermatogonial and Sertoli cell
      proliferation, and we examined the expression of activin/BMP type II and type I
      receptors. We used in vitro cultured testis fragments from 7-day-old mice, highly
      purified populations of somatic and germ cells and total testes from mice of
      different ages. Cell proliferation was assessed by BrdU labelling and [3H]
      thymidine incorporation. Ribonuclease protection assays and Northern blotting
      were performed to analyse receptor expression. RESULTS AND CONCLUSIONS: We have
      demonstrated a stimulatory action of BMP2 and BMP7 in spermatogonia and Sertoli
      cell proliferation respectively. ActRIIB is the type II receptor expressed most
      in spermatogonia, whereas Sertoli cells specifically expressed BMPRIIB, in
      addition to ActRIIB. By contrast, the presence of ActRIIA was undetectable in
      either germ or somatic cells. The type I receptors ActRIA, ActRIB and BMPRIA were
      all found in both cell types, indicating that the observed effect of BMP2 and
      BMP7 on testicular cell proliferation may be mediated by a number of
      combinatorial interactions in the receptor complexes. These findings suggest that
      BMPs are involved in physiological paracrine signalling during the first wave of
      spermatogenesis.

PMID- 15476454
TI  - Mono-allelic expression of the IGF-I receptor does not affect IGF responses in
      human fibroblasts.
AB  - OBJECTIVE: It has been suggested that mono-allelic deletion of the IGF-I receptor
      gene is causally related to severe intrauterine and postnatal growth deficiency
      whereas no IGF-I resistance was observed in the patients' fibroblasts. The
      expression and regulation of the growth-modulating IGF binding proteins (IGFBPs)
      have been investigated in serum and fibroblasts of a short girl with mono-allelic
      loss of the distal long arm of chromosome 15 (15q26.1-qter). PATIENT AND METHODS:
      The mono-allelic loss of the IGF-I receptor (IGF1R) gene was confirmed in a child
      with prenatal and severe postnatal growth retardation by fluorescence in situ
      hybridization, and was evaluated on the protein level in fibroblasts of the
      patient by FACS analysis and IGF cross-linkage. Additionally, expression of
      IGFBPs and cell-mediated degradation of IGFBP-3 were examined in the patient's
      fibroblasts. RESULTS: Levels of GH, IGF-I, and IGFBP-3 were above the 95th
      percentile in the serum of the 3-year-old girl with a mono-allelic deletion of
      the IGF1R gene, suggesting IGF-I resistance. In the patient's fibroblasts the IGF
      I receptor concentration was half that in control cells. Whereas the pattern of
      secreted IGFBPs in response to IGFs was not altered, the abundance of secreted
      IGFBPs was higher in the patient's cells than in controls. Moreover, fibroblast
      mediated degradation of 125I-labeled IGFBP-3 appears to be reduced in the
      patient's fibroblasts. The higher abundance of IGFBPs in the patient's
      fibroblasts might be responsible for the lack of IGF-I-stimulated [alpha-1
      14C]methylaminoisobutyric acid transport. CONCLUSION: Our results suggest that
      the expression and regulation of IGFBPs in tissues from patients with mono
      allelic deletion of the IGF-I receptor gene may lead to IGF sequestration and
      contribute to IGF-I resistance and growth retardation.

PMID- 15476455
TI  - Functional consequences of stress-related suppression of adult hippocampal
      neurogenesis - a novel hypothesis on the neurobiology of burnout.
AB  - BACKGROUND: Burnout is generally recognized as a work-related stress-induced
      condition associated with memory problems, fatigue, a sense of inadequacy, and
      depressed mood. Neurogenesis, the formation of new neurons in the human adult
      brain, provides a newly discovered dimension of brain plasticity. OBJECTIVES: In
      a novel theory, we propose that the failure of adult hippocampal neurogenesis may
      provide the biological and cellular basis for altered brain plasticity in stress
      related syndromes like burnout. METHODS: A number of recent animal studies have
      shown that the rate of neurogenesis in the adult hippocampus may provide an
      important neurobiological correlate to the symptoms of stress. RESULTS: As of
      yet, the normal physiological function of new neurons in the adult hippocampus
      remains unresolved although a number of studies and reviews indicate the
      importance of neurogenesis for memory and learning. CONCLUSION: In line with this
      hypothesis, we propose burnout to be an exponent of stress-mediated decrease in
      adult neurogenesis leading to a decreased ability to cope with stress through
      decreased hippocampal function possibly involving a disturbed hippocampal
      regulation of the hypothalamo-pituitary-adrenal axis (HPA axis).

PMID- 15476456
TI  - A population-based study of survival and discharge status for survivors after
      head injury.
AB  - OBJECTIVES: Creation of a basis for the planning of rehabilitation after head
      injury in Denmark. MATERIALS AND METHODS: Patients with cranial fractures or
      traumatic cerebral lesions occurring in Denmark in 1979-93 were identified by
      computerized searches in the national hospital register. Kaplan-Meier survival
      functions were calculated for these two categories. Hospital records for a random
      sample of 389 survivors in 1997 after cranial fracture, acute brain lesion or
      chronical subdural haematoma, which occurred in 1982, 1987 and 1992 in patients
      aged 15 years or more at injury, were reviewed. Survivors were characterized by
      age, gender, place and severity of injury, as well as neurophysical, speech and
      mental deficits at discharge from hospital. RESULTS: Acute/subacute mortality of
      hospitalized patients was 27% for cerebral lesions and 4% after cranial fracture.
      As attrition by death outweighed the decreasing incidence with time, the point
      prevalence of survivors in 1997 after brain lesions occurring in 1982, 1987 or
      1992 was nearly the same, averaging 8.4 per 100 000 of the population above age
      14. Half of them were severe, as defined by initial Glasgow Coma Score < 9 for
      more than 6 h. There was no tendency with time of injury with regard to
      percentage occurrence of neurophysical, speech or mental deficits at discharge.
      The calculated number of candidates for rehabilitation of personal activities of
      daily life briefly after injury was 9.8 per 100 000 with cerebral lesion and 1.2
      per 100 000 with cranial fracture. The severest 1.5 per 100 000 per year were
      candidates for early intensive centralized rehabilitation in special centres.
      Five years after injury, < 0.13 per 100 000 population survived in the vegetative
      state. CONCLUSION: In this population-based study, survival after cranial
      fracture and cerebral lesion was described quantitatively through Kaplan-Meier
      survival distributions. Besides, patterns of severity, neurophysical and mental
      sequelae among survivors 5, 10 and 15 years post-injury were described. It was
      shown by examples how the study has been useful already for the planning of
      rehabilitation according to a national strategy from 1997 in Denmark. Besides,
      the results may serve as a reference for comparison with future studies.

PMID- 15476457
TI  - Relationships between epilepsy-related factors and memory impairment.
AB  - OBJECTIVES: In this study, we will explore the effect of epilepsy-related factors
      such as: 'type of epilepsy, 'site and side of focus localisation' and 'age at
      onset', as well as four seizure-related factors: 'years with continuing
      seizures', 'seizure type' and 'seizure frequency', and the treatment factor
      'adverse effects of the medication', on memory impairment. Additionally, we
      explored whether these epilepsy factors are related to different aspects of
      memory, i.e. short-term recall vs long-term recall, learning, and verbal memory
      vs non-verbal memory. MATERIAL AND METHODS: A total of 252 patients with epilepsy
      and subjective memory complaints were consecutively included from the three
      epilepsy centres in the Netherlands. To assess memory functions the Wechsler
      Memory Scale-Revised (WMS-r), and the Dutch version of the California Verbal
      Learning Test for verbal list learning, was administered. RESULTS: A multivariate
      analysis of variance (MANOVA) did not show statistically significant effects of
      the epilepsy factors on memory for the total study sample. For the patients with
      a unilateral epileptogenic focus in the temporal lobes, MANOVA showed
      statistically significant effects of lateralisation, with most impairment for
      patients with left temporal lobe epilepsy and, independently, seizure frequency
      and 'years with seizures'. CONCLUSION: We may conclude that epilepsy-related
      dysfunctions in the temporal lobe are the dominant risk factor for developing
      memory problems, specifically verbal memory problems (verbal learning and
      problems consolidating verbal information), with more severe impairments with
      continuing seizures and when seizure frequency is high.

PMID- 15476458
TI  - Visual field defects after temporal lobectomy -- comparing methods and analysing
      resection size.
AB  - OBJECTIVES: The frequency of visual field defects (VFD) after temporal lobe
      resections (TLR) was compared for two types of TLR and VFD frequency was
      correlated to resection size. METHODS: Pre- and post-operative perimetry results
      were analysed for 50 patients with TLR for medically intractable epilepsy. Thirty
      three patients had a classical TLR and 17 had a TLR with less lateral extension.
      Post-operative MRIs were studied in 34 patients by scoring resection size in 12
      compartments in the temporal lobe. RESULTS: Twenty-five patients developed a VFD.
      In the classical TLR group, 16 of 33 developed a VFD, compared with nine of 17 in
      the other group. The resection points were higher for the VFD group in the most
      anterior compartment studied, in the superior temporal gyrus. CONCLUSIONS: There
      was no clearcut difference in VFD frequency between the surgical methods studied.
      However, the compartmentalized analysis disclosed a relation between the extent
      of resection in the anterior part of the superior temporal gyrus and VFD
      frequency.

PMID- 15476459
TI  - Visually evoked blood flow responses and vasoneuronal coupling in partial
      epilepsy.
AB  - OBJECTIVES: Increased metabolic demand is coupled with increased regional blood
      flow. The decreased vasoreactivity in epileptic patients however, prompts an
      impact of epileptic dysfunction on vasoneuronal coupling. MATERIAL AND METHODS:
      Blood flow velocities during visual stimulation were monitored by TCD in both
      posterior cerebral arteries in 20 epileptic patients and 20 control persons,
      response-amplitudes (RA) and pulsatility indices (PI) were analyzed. RESULTS: The
      RAs were significantly smaller in patients than in controls (28.4 +/- 5.7% vs
      38.4 +/- 10.2%; P < 0.001). RAs were larger in the right side and these right
      sided responses were significantly smaller in patients with right-sided vs left
      sided epileptic foci (27.9 +/- 5.5% vs 36.1 +/- 4.5%; P < 0.005). The PI during
      stimulation was significantly larger in patients than in controls (0.92 +/- 0.11
      vs 0.74 +/- 0.15; P < 0.001). CONCLUSION: Our data suggest an impaired
      vasoneuronal coupling in focal epilepsy, and support the view that the right
      hemisphere might be more important for color processing.

PMID- 15476460
TI  - Emotional responses during unilateral amobarbital anesthesia: differential
      hemispheric contributions?
AB  - OBJECTIVES: To explore (1) effects of test and subject variables in determining
      euphoric and dysphoric responses during unilateral amobarbital anesthesia and (2)
      which cerebral areas contribute to the emotional responses. METHOD: Incidence of
      euphoric and dysphoric reactions during left- and right-sided amobarbital
      anesthesia of the internal carotid artery (ICA) and selective anesthesia of the
      middle cerebral (MCA) and the posterior cerebral (PCA) artery was recorded. The
      sample comprised 270 Norwegians (6-61 years), and a total of 562 injections were
      performed under conditions endeavoring to calm down the patients. RESULTS: The
      overall incidence of observed emotional responses during ICA anesthesia was
      21.5%, euphoric reactions being about 10 times more frequent than dysphoric. The
      incidence of euphoric reactions, however, was not significantly higher under
      right- than under left-sided anesthesia, and dysphoric reactions were not more
      frequent under left- than under right-sided anesthesia. Indeed, 13 patients
      showed elevated mood under both right- and left-sided anesthesia. Anesthesia of
      the territories of ICA and MCA gave rise to similar results, while no cases of
      mood change were observed under selective PCA anesthesia. CONCLUSION: It is
      concluded that unilateral amobarbital anesthesia as such, irrespective of side,
      may trigger both euphoric and dysphoric responses. The relative frequency
      obtained is influenced importantly both by the emotional responsiveness of the
      subjects and the emotional climate of the test situation. Finally, it is
      suggested that brain regions supplied by the PCA contribute less to modulation of
      euphoric and dysphoric responses than those supplied by the MCA or the ICA.

PMID- 15476461
TI  - Impaired wakefulness is associated with reduced anterior cingulate CBF in
      patients with normal pressure hydrocephalus.
AB  - OBJECTIVE: To evaluate if impaired wakefulness (IW) in normal pressure
      hydrocephalus (NPH) is associated with reduced blood flow in regions associated
      with the brain arousal system. METHOD: NPH (n = 28) patients were studied before
      and after surgery. Wakefulness was assessed using a new developed scale. Relative
      regional cerebral blood flow (rrCBF) was quantified using SPECT and rectangular
      regions of interest analysis. RESULTS: Sixteen patients presented with IW at
      baseline and in 14 of these, IW vanished after surgery. Patients presenting with
      IW had reduced rrCBF in the anterior cingulate cortex compared with those
      without. After surgery, rrCBF increased significantly in thalamic, frontal and
      hippocampal grey matter regions. Increased hippocampal rrCBF correlated with
      increased basal frontal rrCBF (r = 0.64). In patients where IW vanished after
      surgery, rrCBF increased in the mesencephalon, hippocampus and the frontal
      association cortex. The postoperative increase in wakefulness correlated with
      increased rrCBF in frontal (r = 0.74) and parietal (r = 0.65) association cortex
      areas. CONCLUSION: IW in NPH is associated with reduced rrCBF in the anterior
      cingulate cortex. Improved wakefulness following surgery corresponds to rrCBF
      increments in the frontal association cortex. This study provides support for a
      functional coupling between frontal, hippocampal, thalamic and mesencephalic
      rrCBF in NPH at large.

PMID- 15476462
TI  - Occurrence of multiple sclerosis in central Finland: a regional and temporal
      comparison during 30 years.
AB  - OBJECTIVE: We estimated the prevalence and incidence of multiple sclerosis (MS)
      in central Finland up to 2000. Rates were compared with those in other areas in
      Finland. MATERIAL AND METHOD: MS cases were identified in the hospital registry
      by ICD codes for demyelinating diseases from 1979 to 2000. Cases with definite MS
      were included. Incidence and prevalence were calculated with 95% CI and
      standardization was performed using direct method. RESULTS: In 1993 prevalence
      was 59/10(5) (n = 153). Incidence in 1979-93 was 3.8/10(5) person-years (n =
      126). Rates are similar to average in areas with known rates of MS in Finland but
      substantially less than the over twofold MS risk in the neighbouring district
      Seinajoki. Extended follow-up to 2000 in central Finland showed increasing
      prevalence up to 105/10(5) (n = 277) and a significant increase in incidence 1994
      98 up to 9.2/10(5) (n = 105). At the same time the diagnostic use of MRI
      increased up to 97%. CONCLUSION: Central Finland represents an average risk area
      of MS when compared with other areas of Finland but still a high risk in global
      comparison. The recent rapid increase in both prevalence and incidence is largely
      accounted for by increased use of MRI.

PMID- 15476463
TI  - Beta-trace protein as sensitive marker for liquorrhea.

PMID- 15476465
TI  - Assessing long-term nephron loss: is it time to kick the CAN grading system?

PMID- 15476466
TI  - Significance of anticardiolipin antibodies on short- and long-term allograft
      survival and function following kidney transplantation.

PMID- 15476467
TI  - Retransplantation after post-transplant lymphoproliferative diseases (PTLD): when
      is it safe?

PMID- 15476468
TI  - Mathematical models and behavior: assessing delta MELD for liver allocation.

PMID- 15476469
TI  - Ethical issues in split versus whole liver transplantation.
AB  - Technologic advances in split liver transplantation have resulted in an ethical
      dilemma. Although splitting a liver maximizes the number of patients receiving an
      organ transplant, it may increase the morbidity and mortality for the individual
      patient receiving the split liver. This essay explores the ethical issues
      involved in the allocation of split livers, and proposes general policy
      guidelines for the allocation of split versus whole liver transplants.

PMID- 15476470
TI  - What's new--what's hot in basic science: American Transplant Congress 2004.
AB  - The field of transplantation biology has, in the past year, given rise to several
      improved models explaining the in vivo phenomena of allograft rejection and
      acceptance. Although T-cells remain central participants in allorecognition,
      innate immune cells are increasingly recognized as critical. There is also
      growing acceptance that T-cell responses can vary widely not only based on their
      repertoire, but also on their immune experience in general, and their
      participation in homeostatic proliferation. Additional signaling pathways and
      molecules, such as the Janus kinase pathway and vascular endothelial growth
      factor have been added to those recognized as important in pharmacologic
      immunosuppression, and the concepts of regulation, once polarized between CD8+
      and CD4+ camps, have begun to converge upon a recognition that there are many
      phenotypes of regulatory cells. In addition to improved basic science, several
      translational fields have accelerated in the past 12 months. Promising and
      clinically applicable islet transplant regimens have been developed and look
      appropriate for near-term clinical trials. Significant progress in discordant
      xenotransplantation is also apparent. This manuscript will review the past year
      in transplantation science as reported at the 2004 American Transplant Congress.

PMID- 15476471
TI  - What's new--what's hot in clinical science: American Transplant Congress 2004.
AB  - The American Transplant Congress 2004, held in Boston last May, was the biggest
      conference in the history of the event, with over 4000 attendees. A wide variety
      of clinical topics were presented and discussed, all advancing the field of solid
      organ transplantation. This manuscript will attempt to summarize the
      presentations at the meeting. Particularly 'hot' clinical topics included the
      recent passage of a law to increase organ recovery, the use of expanded criteria
      kidney donors, a new model for the allocation of deceased donor lungs, survival
      following liver transplantation and its potential effect on liver allocation and
      the use of novel immunosuppressive drugs.

PMID- 15476473
TI  - Treatment with anti-MHC-class-II antibody postpones kidney allograft rejection in
      primates but increases the risk of CMV activation.
AB  - Treatment of kidney graft recipients with antibodies that may specifically
      suppress the anti-donor response would be an ideal situation to prevent graft
      rejection. MHC class-II-specific antibodies and, in particular, DR specific
      antibodies have often been proposed as treatment to prevent antigen presentation,
      and thus graft destruction. Here we report an attempt to prevent graft rejection
      using a humanized MHC class-II-specific monoclonal antibody CDP855 in a
      cynomolgus monkey kidney graft model. A modest delay in graft rejection was
      observed when the antibody was given only on days 0, 1 and 2 after
      transplantation. Unexpectedly 50% of the animals succumbed of a viral infection,
      most likely CMV in two of three cases, prior to graft rejection in the first week
      post-transplantation. We speculate that the antibody treatment triggered CMV
      activation, possibly as a consequence of the activation of factors such as NF
      kappab by the interaction of the antibody and its target cells.

PMID- 15476474
TI  - Evidence for cooperativity in the rejection of cardiac grafts mediated by CD4 TCR
      Tg T cells specific for a defined allopeptide.
AB  - Understanding the mechanisms of rejection of organs transplanted between
      unrelated individuals is confounded by the complexity of the alloantigens and the
      diversity of T cells responding to these alloantigens. To circumvent these
      problems, we developed a transgenic (Tg) C57BL/6 model system in which the T-cell
      receptor (TCR) expressed by CD4 T cells is specific for a defined allogeneic H
      2Kd peptide and the cardiac donor expressed H-2Kd as a transgene on the C57BL/6
      background (B6.Kd). These TCR Tg T cells were previously shown to mediate rapid
      rejection of a B10.D2 cardiac allograft when transferred to Rag1 recipients,
      demonstrating that the "indirect" pathway of allorecognition is sufficient for
      complete rejection in the absence of other T cells or antibody. Here, we report
      that B6.Kd hearts were rejected in an accelerated fashion by Rag1(-/-) TCR Tg T
      cells adoptively transferred to normal B6 recipients. Rejection in this model was
      associated with large myocardial infarcts and significant coronary artery
      inflammation. Moreover, transferred TCR Tg CD4+ cells mediated allograft injury
      without the requirement for cytotoxic function from recipient-derived CD8 T
      cells. A non-linear relationship was observed between the initial precursor
      frequency of the antigen-specific TCR Tg cells and the ultimate tempo of acute
      rejection, which is taken as evidence for cooperativity between components of the
      system.

PMID- 15476475
TI  - Lower incidence of chronic allograft nephropathy at 1 year post-transplantation
      in patients treated with mycophenolate mofetil.
AB  - Chronic allograft nephropathy (CAN) is the main cause of graft failure after the
      first year of transplantation. This prospective, centrally randomized, open-label
      study was conducted to examine the possibility that mycophenolate mofetil (MMF)
      can prevent the emergence of CAN. The incidence of biopsy-proven CAN at 1 year
      was compared between two cyclosporine-based regimens comprising either
      mycophenolate mofetil (MMF) or azathioprine (AZA). The AZA group (n = 34) and the
      MMF group (n = 37) were balanced for all baseline characteristics of donors and
      recipients, the pre-existence of renal lesions on donor biopsy, the incidence of
      delayed graft function and acute rejection. Based on an intent-to-treat analysis,
      the number of patients with CAN at 1 year post-transplantation was significantly
      reduced in the MMF group (17/37-46%) compared with the AZA group (24/34-71%) (p =
      0.03). When observed data were considered, 56/71 (78.8%) patients had a 1-year
      biopsy, and the number of patients with CAN was significantly lowered in the MMF
      group (9/29-31%) compared with the AZA group (17/27-63%) (p = 0.01). These
      results suggest a beneficial effect of MMF on the incidence of CAN at 1 year post
      transplantation.

PMID- 15476476
TI  - De novo kidney transplantation without use of calcineurin inhibitors preserves
      renal structure and function at two years.
AB  - We performed a randomized prospective trial comparing calcineurin inhibitor (CNI)
      free to CNI-based immunosuppression to determine the impact on renal function,
      structure and gene expression. Sixty-one kidney recipients treated with
      basiliximab mycophenolate mofetil (MMF) and prednisone (P) were randomly assigned
      to concentration-controlled sirolimus or cyclosporine. Two years post-transplant
      55 patients underwent renal function studies, 48 (87%) underwent transplant
      biopsies; all classified by Banff scoring and 41 by DNA microarrays. Comparing
      sirolimus/MMF/P to cyclosporine/MMF/P there was a significantly lower serum
      creatinine (1.35 vs. 1.81 mg/dL; p = 0.008), higher Cockroft-Gault glomerular
      filtration rate (GFR) (80.4 vs. 63.4 mL/min; p = 0.008), iothalamate GFR (60.6
      vs. 49.2 mL/min; p = 0.018) and Banff 0 (normal) biopsies (66.6 vs. 20.8%; p =
      0.013). Regression analysis of calculated GFRs from 1 to 36 months yielded a
      positive slope for sirolimus of 3.36 mL/min/year, and a negative slope for
      cyclosporine of -1.58 mL/min/year (p = 0.008). Gene expression profiles from
      kidneys with higher Banff chronic allograft nephropathy (CAN) scores confirmed
      significant up-regulation of genes responsible for immune/inflammation and
      fibrosis/tissue remodeling. At 2 years the sirolimus-treated recipients have
      better renal function, a diminished prevalence of CAN and down-regulated
      expression of genes responsible for progression of CAN. All may provide for an
      alternative natural history with improved graft survival.

PMID- 15476477
TI  - Significance of anticardiolipin antibodies on short and long term allograft
      survival and function following kidney transplantation.
AB  - The significance of anticardiolipin antibodies (ACAs) prior to renal
      transplantation is unclear. We studied a cohort of 337 patients who underwent
      renal transplantation from 1996 to 2001. Follow-up continued until allograft
      loss, patient death or 31 December 2002. The primary outcome was a composite
      endpoint of death-censored allograft loss or a 25% reduction in estimated
      glomerular filtration rate (GFR) from 1-month post-transplant. Secondary outcomes
      were allograft loss, a 25% reduction in GFR, acute rejection and creatinine at 1
      year. IgG and IgM ACA titers were positive (> or =15) in 18.1% of recipients.
      There were no significant differences at baseline between recipients, except
      coumadin therapy in those with positive ACA titers (20% vs. 7.4%). Post
      transplant, there was no increase in the primary outcome in ACA-positive
      patients, even after adjustment for anticoagulation with coumadin (HR = 1.42
      [0.68, 2.96]). There was no difference in secondary outcomes between those with
      or without positive titers. Two of five patients with very high titers (>50) who
      were not anticoagulated had early graft loss. A positive ACA titer prior to
      kidney transplantation was not associated with inferior renal outcomes after
      transplantation, although more research is required to address the prognostic
      significance of very high ACA titers.

PMID- 15476478
TI  - Predicted lifetimes for adult and pediatric split liver versus adult whole liver
      transplant recipients.
AB  - Split liver transplantation allows 2 recipients to receive transplants from one
      organ. Comparisons of predicted lifetimes for two alternatives (split liver for
      an adult and pediatric recipient vs. whole liver for an adult recipient) can help
      guide the use of donor livers. We analyzed mortality risk for 48,888 waitlisted
      candidates, 907 split and 21,913 whole deceased donor liver transplant recipients
      between January 1, 1995 and February 26, 2002. Cox regression models for
      pediatric and adult patients assessed average relative wait list and post
      transplant death risks, for split liver recipients. Life years gained compared
      with remaining on the waiting list over a 2-year period were calculated. Seventy
      six splits (152 recipients) and 24 re-transplants resulted from every 100 livers
      (13.1% [adult] and 18.0% [pediatric] 2-year re-transplant rates, respectively).
      Whole livers used for 93 adults also utilized 100 livers (re-transplant rate
      7.0%). Eleven extra life years and 59 incremental recipients accrued from each
      100 livers used for split compared with whole organ transplants. Split liver
      transplantation could provide enough organs to satisfy the entire current demand
      for pediatric donor livers in the United States, provide more aggregate years of
      life than whole organ transplants and result in larger numbers of recipients.

PMID- 15476479
TI  - Predicting survival among patients listed for liver transplantation: an
      assessment of serial MELD measurements.
AB  - We examined whether consideration of repeated model for end-stage liver disease
      (MELD) measurements for patients listed for liver transplantation improves
      predictive value beyond current MELD alone. Clinical data were extracted for all
      adult primary liver transplantation candidates from our institution who were
      listed with the United Network for Organ Sharing (UNOS) between 1990 and 1999.
      Serum creatinine, bilirubin, and international normalized ratio (INR) were
      obtained from an institutional laboratory database. Cox models were constructed
      using current MELD, change in MELD (Delta), and number of MELD scores to predict
      survival on the waiting list. Eight hundred and sixty-one patients met inclusion
      criteria, 639 underwent transplantation, and 80 died while waiting. A one-unit
      increment in current MELD imparted significant hazard ratios ranging from 1.12 to
      1.19 in all models. Delta MELD was predictive of mortality univariately, but less
      predictive when current MELD was included, and not predictive when considered
      with both current and number of MELD scores. Overall, current MELD is the single
      most important determinant of mortality risk on the waiting list. Delta MELD is
      predictive of death only within 4 d of the event; however, part of this
      correlates with the dying process itself, thus limiting Delta MELD's utility in
      survival prediction models.

PMID- 15476480
TI  - Influenza vaccination in orthotopic liver transplant recipients: absence of post
      administration ALT elevation.
AB  - Influenza vaccination has reduced life-threatening complications from influenza
      virus infection in adult liver transplant recipients. We evaluated changes in
      aminotransferase level and immunogenicity of influenza vaccination in liver
      transplant recipients. Fifty-one liver transplant recipients were administered a
      standard dose of the 2002-2003 inactivated trivalent influenza vaccine. ALT
      values were measured at baseline, 1 week and 4-6 weeks postvaccination. Antibody
      responses to each component of the vaccine were measured at baseline and after 4
      6 weeks by a hemagglutination inhibition (HAI) assay. Response was defined as an
      HAI titer > or = 1: 40 and/or a 4-fold increase in antibody titers from baseline.
      An ALT elevation was defined as a rise of > or = 50% from baseline. There was no
      difference in the median rise in ALT value between seroconverters and
      nonseroconverters. A significant number of recipients developed potentially
      protective antibody titers (p-value < 0.0001). At less than 4 months post
      transplantation, 1/7 (14%), at 4-12 months, 6/9 (67%), and after 12 months, 30/35
      (86%) subjects responded to the H1 strain. Of 51 recipients, one HCV (-)
      recipients vaccinated within 3 months of transplantation developed acute cellular
      rejection. Influenza virus vaccination is not associated with allograft rejection
      or ALT flares in liver transplant recipients.

PMID- 15476481
TI  - Thiopurine S-methyltransferase genotype predicts azathioprine-induced
      myelotoxicity in kidney transplant recipients.
AB  - Azathioprine (AZA) is an immunosuppressive prodrug that undergoes metabolism by
      thiopurine S-methyltransferase (TPMT). Eighty to ninety-five percent of low or
      deficient TPMT enzyme activity is genetically determined by the presence of three
      nonfunctional mutant alleles: TPMT*2, TPMT*3A and TPMT*3C. Using TPMT as a
      pharmacogenetic paradigm, we explored the association between these genetic
      mutations and development of adverse drug effects in an ethnically diverse renal
      transplant population receiving azathioprine. Biochemical and clinical data were
      retrospectively evaluated during the first four weeks after kidney
      transplantation. TPMT nonfunctional mutant alleles were identified by polymerase
      chain reaction-based methods. Of 89 patients initially consented, 36 met
      inclusion criteria for this retrospective study. Five patients possessing a
      single TPMT nonfunctional mutant allele were identified: TPMT*3A: n = 2
      Caucasians; TPMT*3B: n = 1 Caucasian; TPMT*3C: n = 2 African-Americans. TPMT
      nonfunctional mutant alleles were associated with significant reductions in
      hematological indices and a significant increase in cyclosporine plasma
      concentrations in the first month post-transplant. TPMT genotype was an
      independent predictor for hemoglobin, hematocrit and red blood cell changes while
      mean azathioprine dose (mg/kg/day), azathioprine dose (mg/kg/day) at day 30 and
      cyclosporinemia at day 30 were not. Prospective application of pharmacogenetic
      principles may assist in optimization of immunosuppressive drug therapy and
      minimize drug toxicities.

PMID- 15476482
TI  - Risk factor screening scale to optimize treatment for potential heart transplant
      candidates under extracorporeal membrane oxygenation.
AB  - We developed a risk factor-scaling score (RFSS) to select which patients
      supported by extracorporeal membrane oxygenation (ECMO) were suitable for
      ventricular assist device (VAD) implantation or heart transplantation (HTx). A
      total of 78 patients supported with ECMO for more than 48 h due to cardiac origin
      were included in this study. Patients were categorized into two groups based on
      the outcomes: the poor outcome group (n = 33) consisted of for those who later
      died or were later excluded from VAD or HTx; the favorable outcome group (n = 45)
      consisted of those who were weaned off ECMO finally and survived or were deemed
      suitable candidates for VAD or HTx. Seven risk factors were significant according
      to univariate analyses. Based on the regression coefficients of multivariate
      analysis, the RFSS was developed: (lung dysfunction x 7) + (systemic infection x
      3) + (peak lactate > 3 mmole/L x 3) + (kidney dysfunction x 2) + (creatine kinase
      > 10,000 U/L x 1). Patients with an RFSS of 7 or more were be allocated to the
      poor outcome group. The RFSS was validated by another group of 30 patients with
      good correlation. The RFSS provides a way to predict which ECMO-supported
      patients are suitable candidates for VAD implantation or HTx.

PMID- 15476483
TI  - Performance of different prediction equations for estimating renal function in
      kidney transplantation.
AB  - Numerous formulas have been developed to estimate renal function from
      biochemical, demographic and anthropometric data. Here we compared renal function
      derived from 12 published prediction equations with glomerular filtration rate
      (GFR) measurement by plasma iohexol clearance as reference method in a group of
      81 renal transplant recipients enrolled in the Mycophenolate Mofetil Steroid
      Sparing (MY.S.S.) trial. Iohexol clearances and prediction equations were carried
      out in all patients at months 6, 9 and 21 after surgery. All equations showed a
      tendency toward GFR over-estimation: Walser and MDRD equations gave the best
      performance, however not more than 45% of estimated values were within +/-10%
      error. These formulas showed also the lowest bias and the highest precision: 0.5
      and 9.2 mL/min/1.73 m2 (Walser), 2.7 and 10.4 mL/min/1.73 m2 (MDRD) in predicting
      GFR. A significantly higher rate of GFR decline ranging from -5.0 mL/min/1.73
      m2/year (Walser) to -7.4 mL/min/1.73 m2/year (Davis-Chandler) was estimated by
      all the equations as compared with iohexol clearance (-3.0 mL/min/1.73 m2/year).
      The 12 prediction equations do not allow a rigorous assessment of renal function
      in kidney transplant recipients. In clinical trials of kidney transplantation,
      graft function should be preferably monitored using a reference method of GFR
      measurement, such as iohexol plasma clearance.

PMID- 15476484
TI  - Initial blood washout during organ procurement determines liver injury and
      function after preservation and reperfusion.
AB  - Organ procurement is the first step toward effective liver preservation and
      comprises a thorough washout of blood components from the microvasculature. To
      study the efficacy of optimal blood washout of the liver, three groups were
      compared including low-pressure perfusion with UW-CSS (12 mmHg, group A), which
      is the routine method in clinical practice, high-pressure perfusion with UW-CSS
      (100 mmHg, group B) and low-pressure perfusion with modified UW solution (12
      mmHg, group C). After procurement all livers were preserved in original UW-CSS
      for 0, 24 or 48 h, followed by reperfusion in oxygenated Williams Medium E for 24
      h at 37 degrees C. Histology results of livers procured in group A, showed good
      hepatocyte viability but also remaining erythrocytes. However, injury parameters
      were high and ATP concentrations were low. No functional differences were found.
      Group B, high pressure, and group C, modified UW-CSS, both showed better results.
      High-pressure washout is preferable since the warm ischemia time during
      procurement is short. We propose to use high-pressure UW-CSS perfusion for the
      initial blood washout of the donor liver instead of the usually used low-pressure
      washout.

PMID- 15476486
TI  - Evaluation of sun-protective practices of organ transplant recipients.
AB  - The incidence, morbidity and mortality of skin cancer are markedly increased in
      organ transplant recipients. Efforts aimed at reducing sun exposure through sun
      avoidance, sunscreens and sun-protective clothing are the most effective means to
      reduce the risk of skin cancer. We evaluated the sun-protective behaviors of 205
      transplant recipients. Twenty-three percent of transplant patients continued to
      seek a tan. Thirty percent of patients did not use sunscreens, and of those
      patients who did, less than 5% were committed to using them daily. Thirty-seven
      percent of patients frequently wore hats and 39% of patients frequently wore
      additional clothing to block the sun. When data were stratified according to
      patient age, gender or skin phototype, we identified preferences for specific sun
      protective methods. These data strongly suggest that many transplant recipients
      do not use adequate sun protection. Further study of strategies to encourage the
      use of sun protection among transplant patients is needed to reduce the incidence
      of skin cancer.

PMID- 15476485
TI  - Steroid sparing with tacrolimus and mycophenolate mofetil in renal
      transplantation.
AB  - Evidence suggests that steroid sparing in renal transplantation is associated
      with good outcomes, although there are limited data regarding steroid sparing in
      Tacrolimus and Mycophenolate Mofetil (MMF)-based regimes. In this study we
      describe the use of these agents in 101 consecutive patients undergoing renal
      transplantation using only a 7-day course of prednisolone. Median follow-up was
      33 months (range 18-44). Patient and graft survival at 1 year were 100% and 98%,
      respectively. The acute rejection rate at both 6 and 12 months was 19%, with two
      episodes beyond 12 months. Anti-CD25 monoclonal antibody (anti-CD25 mAb) was
      administered to 25 patients at high immunological risk: a trend toward a lower
      rejection rate was seen in these patients compared with those at lower risk but
      not receiving induction therapy (8% vs. 22%; p = 0.11). Two patients experienced
      recurrent rejection. Of the twenty-three rejection episodes in total, 26% showed
      vascular involvement. Allograft function was preserved at 12 months with a mean
      creatinine of 144 micromol/L and mean estimated glomerular filtration rate (GFR)
      of 55 mL/min. At 12 months, the incidence of post-transplant diabetes mellitus
      was 3.5%. This steroid-sparing regime is associated with excellent patient and
      graft outcomes, and a low incidence of side effects.

PMID- 15476487
TI  - Matching T-cell receptors identified in renal biopsies and urine at the time of
      acute rejection in pediatric renal transplant patients.
AB  - Urinary monitoring of kidney allograft function has been used for many years.
      More recently, molecular identification of cytotoxic T-cell products has been
      used as a diagnostic tool in acute rejection. Monitoring of T-cell infiltrates by
      analysis of the T-cell receptor (TcR) gene usage has been performed on biopsies
      with acute and chronic rejection, but not on urine samples. The aim of this study
      was to identify and compare TRBV gene usage assessing the CDR3 (Complementarity
      Determining Region 3) length distribution and sequence in urine and biopsies of
      pediatric renal allograft patients at the time of acute rejection and compare
      them with peripheral blood. We studied four pediatric renal transplant recipients
      with acute cellular rejection. We identified restricted and matched TRBV CDR3
      spectratypes with overexpressed TRBV families and show identical, clonally
      expanded TRBV CDR3 sequences in all four patients present in the urine and renal
      allograft. We demonstrate that urinary monitoring can detect graft-infiltrating
      lymphocytes in acute rejection and may have a role in the monitoring of renal
      transplants.

PMID- 15476488
TI  - Predictors of success in conversion from calcineurin inhibitor to sirolimus in
      chronic allograft dysfunction.
AB  - Chronic allograft dysfunction (CAD) is a major cause of graft loss in long-term
      kidney transplant recipients. To identify predictors of successful conversion
      from calcineurin inhibitor (CNI) to sirolimus (SRL) we investigated 59 renal
      transplant patients with CAD without histological signs of acute rejection. They
      received 12-15 mg SRL once, then 4-5 mg/day, target trough level 8-12 ng/mL. CNI
      dose was reduced by 50% simultaneously, and withdrawn at 1-2 months. Concomitant
      immunosuppression remained unchanged. After 1 year patient survival was 100% and
      graft survival 92%. In responders (54%) creatinine improved (2.75 +/- 0.75 to
      2.22 +/- 0.64 mg/dL; p < 0.01). In nonresponders (46%) creatinine deteriorated
      (3.15 +/- 1.02 to 4.44 +/- 1.60 mg/dL; p < 0.01). Baseline renal function did not
      differ, however, baseline proteinuria (519 +/- 516 vs. 1532 +/- 867 mg/day, p <
      0.01), histological grade of chronic allograft nephropathy (CAN) (1.2 +/- 0.5 vs.
      1.9 +/- 0.6; p < 0.01), grade of vascular fibrous intimal thickening (1.2 +/- 0.7
      vs. 1.7 +/- 0.7; p = 0.048) and number of acute rejections before conversion
      (0.73 +/- 0.69 vs. 1.27 +/- 0.96; p < 0.05) differed significantly between
      responders and nonresponders. In a multivariate analysis low proteinuria was the
      only independent variable. Proteinuria below 800 mg/day has a positive predictive
      value of 90%. Proteinuria at conversion below 800 mg/day is the only independent
      predictor for positive outcome in conversion from CNI to SRL in CAD.

PMID- 15476489
TI  - Development of diabetes mellitus following kidney transplantation: a Canadian
      experience.
AB  - The onset of diabetes mellitus following kidney transplantation or post
      transplant diabetes mellitus (PTDM) is now recognized as being an increasingly
      common complication that is associated with poor graft and patient survival. The
      incidence and clinical correlates of PTDM in a Canadian kidney transplant
      population has not been examined and may vary based on differences in
      demographics (i.e. race). Furthermore, little information exists on the
      association of variables such as cumulative dose of corticosteroids and trough
      calcineurin inhibitor levels and PTDM. We examined all recipients of a kidney
      transplant in our center between 1995 and 2001 and found an overall PTDM rate of
      9.8%. Five clinical factors were independently associated with PTDM: older
      recipient age, deceased donor, hepatitis C antibody status, rejection episode and
      use of tacrolimus (vs. cyclosporine). Furthermore, cumulative corticosteroid dose
      and calcineurin inhibitor trough level were not associated with PTDM. This study
      demonstrates that in a Canadian kidney transplant population that there is a
      significant risk of PTDM following kidney transplantation, and it is therefore
      advisable to minimize this risk.

PMID- 15476490
TI  - A seroprevalence study of west nile virus infection in solid organ transplant
      recipients.
AB  - West Nile virus (WNV) causes severe neurological disease in less than 1% of
      infections. However, meningoencephalitis may be more common in immunosuppressed
      transplant patients. In 2002, a WNV outbreak occurred in our region. To determine
      the spectrum of disease of community acquired WNV infection and assess public
      health behavior patterns in transplant recipients, we carried out a
      seroprevalence study. Patients were enrolled from outpatient transplant clinics
      in October 2002 and sera were screened for WNV. Questionnaires about WNV were
      provided to patients. Eight hundred sixteen organ transplant patients were
      enrolled. The seroprevalence of WNV IgM was 2/816 (0.25%; 95% CI 0.03-0.88%). By
      extrapolation to our entire transplant population of 2360 patients, and using
      data from hospital-based surveillance, the risk of meningoencephalitis in a
      transplant patient infected with WNV is estimated to be 40% (95% CI 16-80%). With
      regards to knowledge and behavior, 56% patients knew of and 47% used at least one
      protective measure against WNV. Only 33% used insect repellent. The risk of
      meningoencephalitis in transplant recipients is much higher than in the general
      population. There is incomplete knowledge and poor rates of compliance amongst
      patients with regards to WNV prevention.

PMID- 15476491
TI  - Stented versus nonstented extravesical ureteroneocystostomy in renal
      transplantation: a metaanalysis.
AB  - Stenting of the extravesical ureteroneocystostomy in renal transplantation is
      controversial. This study is a metaanalysis of 49 published studies over 30 years
      time in which the extravesical technique was used. Stented and nonstented
      anastomoses were compared. One-hundred six articles published between 1973 and
      2002 were reviewed and 49 met criteria for inclusion. Articles were required to
      list original, numeric, previously unpublished data and to report or to describe
      the use of an extravesical ureteroneocystostomy, with or without stent. Data were
      analyzed within separate groups, (1) randomized, controlled trials and (2) case
      series. Data were included from five randomized, controlled trials and 44 case
      series. In the controlled trials group, there were urologic complications in 6 of
      407 stented (1.5%), and 35 of 389 nonstented subjects (9.0%) (p < 0.0001, OR
      0.24, 95% CI 0.10-0.57). In the case-series group, there were urologic
      complications in 137 of 4245 stented (3.2%) and 433 of 9077 nonstented subjects
      (4.8%) (p = 0.007, OR 0.58, 95% CI 0.39-0.86). Renal transplants with stented
      extravesical ureteroneocystostomy have a significantly lower urologic
      complication rate than those with nonstented anastomoses. All five randomized,
      controlled trials individually found stented anastomoses to have a lower
      complication rate and this was confirmed by metaanalysis of these trials and of
      case-series data.

PMID- 15476492
TI  - Reduced incidence of new-onset diabetes mellitus after renal transplantation with
      3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors (statins).
AB  - Statins have anti-inflammatory effects, modify endothelial function and improve
      peripheral insulin resistance. We hypothesized that statins influence the
      development of new-onset diabetes mellitus in renal transplant recipients. The
      records of all previously non-diabetic adults who received an allograft in
      Toronto between January 1, 1999 and December 31, 2001 were reviewed with follow
      up through December 31, 2002. All patients receiving cyclosporine or tacrolimus,
      mycophenolate mofetil and prednisone were included. New-onset diabetes was
      diagnosed by the Canadian Diabetic Association criteria: fasting plasma glucose >
      or =7.0 mmol/L or 2-h postprandial glucose > or =11.1 mmol/L on more than two
      occasions. Statin use prior to diabetes development was recorded along with other
      variables. Cox proportional hazards models analyzing statin use as a time
      dependent covariate were performed. Three hundred fourteen recipients met study
      criteria, of whom 129 received statins. New-onset diabetes incidence was 16% (n =
      49). Statins (p = 0.0004, HR 0.238[0.109-0.524]) and ACE inhibitors/ARB (p =
      0.01, HR 0.309[0.127-0.750]) were associated with decreased risk. Prednisone dose
      (p = 0.0001, HR 1.007[1.003-1.010] per 1 mg/d at 3 months), weight at transplant
      (p = 0.02, HR 1.022[1.003-1.042] per 1 kg), black ethnicity (p = 0.02, HR
      1.230[1.023-1.480]) and age > or =45 years (p = 0.01, HR 2.226[1.162-4.261]) were
      associated with increased diabetes. Statin use is associated with reduced new
      onset diabetes development after renal transplantation.

PMID- 15476493
TI  - Successful renal retransplantation after post-transplant lymphoproliferative
      disease.
AB  - Post-transplant lymphoproliferative disease (PTLD) is a rare but severe
      complication of renal transplantation. Reduction of immunosuppression is
      essential for controlling PTLD but may induce graft loss. Retransplantation after
      PTLD is considered dangerous, because immunosuppressive treatment resumption may
      trigger hematological relapse. We retrospectively report six patients (five
      adults, one child) who underwent a second renal transplantation after
      successfully treated PTLD. Epstein-Barr virus (EBV) serology was positive before
      the first transplantation in all patients except the child. Post-transplant
      lymphoproliferative disease was detected 6.6 months (range 4.5-9.4) after
      transplantation. Lymphoproliferation was always monomorphic, B-cell, and EBV
      related. Post-transplant lymphoproliferative disease was confined to the renal
      allograft (n = 4), multilocular (n = 1) or cerebral (n = 1). Immunosuppression
      tapering (6/6) and transplantectomy (5/6) led to hematological remission in all
      patients. Retransplantation was performed 77 months (range 50-128) after PTLD
      diagnosis. Immunosuppression included steroids (n = 6), ATG (n = 2), anti-CD25 (n
      = 2), cyclosporine (n = 4), tacrolimus (n = 2), mycophenolate mofetil (n = 4) and
      azathioprine (n = 1). After a median follow up of 30 months (range 24-47) patient
      survival was 100%, with no recurrence of PTLD. In conclusion, renal
      retransplantation can be considered in patients with monomorphic PTLD history,
      without major risk of hematological recurrence.

PMID- 15476494
TI  - Rapid progression of native renal artery fibromuscular dysplasia following kidney
      donation.
AB  - Fibromuscular dysplasia is the second commonest anatomical abnormality apart from
      multiple renal arteries in the potential live donors. Pretransplant evaluation of
      the donors may include an angiography to evaluate the renal arteries, and failure
      to recognize renal arterial stenosis, particularly fibromuscular dysplasia, by
      noninvasive methods may eventually lead to hypertension and ischemic renal
      failure. We report a case of fibromuscular dysplasia that was undetected by
      computed tomographic angiography prior to donation. One year after kidney
      donation, it rapidly progressed to severe symptomatic stenosis with hypertension
      and acute renal failure. Following renal artery angioplasty, her blood pressure
      normalized over a period of 2 weeks without any need for antihypertensive
      medications and the serum creatinine returned to her baseline. The acceptability
      of renal donors with fibromuscular dysplasia depends on the age, race and the
      availability of the other suitable donors. Mild fibromuscular dysplasia in a
      normotensive potential renal donor cannot be considered a benign condition. Such
      donors need regular follow-up postdonation for timely detection and treatment.

PMID- 15476495
TI  - EBV positive primary cutaneous CD30+ large T-cell lymphoma in a heart
      transplanted patient: case report.
AB  - Most post-transplant lymphoproliferative disorders (PTLDs) are of B-cell origin,
      whereas T-cell lymphomas rarely occur. We detail the clinicopathological features
      of the first case of Epstein-Barr virus (EBV)-associated primary cutaneous CD30+
      anaplastic large cell lymphoma (ALCL) in the setting of heart transplant. A 71
      year-old patient, 111 months after transplant, presented with multiple cutaneous
      lesions on the left thigh; histological and immunohistochemical examinations led
      to diagnosis of T-cell CD30+ ALCL. In situ hybridization demonstrated the
      presence of EBV-positive tumour cells. The patient received radiotherapy, but he
      relapsed at the same cutaneous site with loco-regional nodal spread. Chemotherapy
      was administered resulting in complete remission; four years later the patient is
      alive and well. Our findings indicate that primary cutaneous EBV+ CD30+ ALCLs
      should be included within the T-cell PTLDs spectrum; further studies are required
      to confirm whether they may be also considered, in transplantation settings, a
      distinct lymphoma subset with relatively favourable outcome.

PMID- 15476499
TI  - A conversation between Darracott Vaughan and Donald S. Coffey.

PMID- 15476496
TI  - Combined 'en bloc' liver and pancreas transplantation in patients with liver
      disease and type 1 diabetes mellitus.
AB  - Liver disease alters the glucose metabolism and may cause diabetes, but this
      condition is potentially reversible with liver transplantation (LTx). Type 1
      diabetes mellitus may be coincidentally present in a LTx candidate and
      immunosuppressive drugs will aggravate diabetes and make its management more
      difficult for posttransplant. In addition, diabetes negatively influences outcome
      after LTx. Therefore, the question arises as to why not transplanting the
      pancreas in addition to the liver in selected patients suffering from both liver
      disease and Type 1 diabetes. We report two cases of en bloc combined liver and
      pancreatic transplantation, a technique originally described a decade ago in the
      treatment of upper abdominal malignancies but rarely used for the treatment of
      combined liver disease and Type 1 diabetes. Both recipients are currently liver
      disease-free and insulin-free more than 2 and 4 years posttransplant,
      respectively. Surgical, medical and immunological aspects of combined liver
      pancreas transplantation are discussed in the light of the existing relevant
      literature.

PMID- 15476500
TI  - Quality of care in urology.

PMID- 15476501
TI  - The place of the augmented rectal pouch in urinary diversion.

PMID- 15476502
TI  - Bicalutamide 150 mg: practical prescribing in patients with early prostate
      cancer.

PMID- 15476503
TI  - Suppressor screening -- a potential new model for understanding the genetic
      components of urological malignancies.

PMID- 15476504
TI  - The expanding indications for laparoscopic radical nephrectomy.

PMID- 15476505
TI  - Conservative vs radical surgery for renal cell carcinoma.

PMID- 15476506
TI  - Three-dimensional imaging in urology.

PMID- 15476507
TI  - Surgical alternatives for treating Peyronie's disease.

PMID- 15476508
TI  - Upper tract tumour after radical cystectomy for transitional cell carcinoma of
      the bladder: incidence and risk factors.
AB  - OBJECTIVE: To review the incidence, pattern and outcome of upper tract
      transitional cell carcinoma (TCC) after radical cystectomy for carcinoma of the
      bladder, and identify risk factors for its development. PATIENTS AND METHODS: The
      records of 235 consecutive patients who had a radical cystectomy and urinary
      diversion for TCC at the authors' institution by one surgeon between January 1992
      and August 2003 were retrospectively reviewed. RESULTS: Five (2%) of 235 patients
      developed an upper tract urothelial tumour. The mean follow-up for all patients
      was 42 months, and was 52.2 months for those with an upper tract tumour. Four of
      the five patients presented with haematuria and one was diagnosed on routine
      follow-up intravenous urography. The mean time to the diagnosis of an upper tract
      tumour was 39.6 months. Of the potential risk factors, only the presence of TCC
      of the prostatic urethra had a statistically significant association with
      eventual upper tract tumour (P < 0.01). At the last follow-up, four patients died
      from urothelial cancer and one was disease-free. CONCLUSIONS: The incidence of
      upper tract tumour after cystectomy for TCC is low; most patients present with
      symptoms (haematuria) and have advanced disease at diagnosis. Patients with
      prostatic urethral involvement at cystectomy are at greater risk of developing
      upper tract tumour.

PMID- 15476509
TI  - Upper tract surveillance in primary bladder cancer follow-up.
AB  - OBJECTIVE: To determine if there is national variation in regimens of upper
      urinary tract surveillance in patients with primary bladder cancer. METHODS: A
      questionnaire was sent to 470 consultant urologists from a British Association of
      Urological Surgeons list in the UK; 301 anonymous replies were received. Two
      replies were incomplete and therefore the results of 299 questionnaires (64%)
      were analysed. RESULTS: Of the 299 surgeons, 19 (6%) use no form of upper urinary
      tract surveillance; 162 (54%) use surveillance in selected patients, i.e. those
      with carcinoma in situ (47%), multiple bladder tumours at first presentation
      (39%) and after cystectomy (70%), and 118 (39%) use upper tract surveillance on
      all patients with a history of bladder cancer. The median (range) screening
      interval was 24 (12-60) months and surveillance continued for a median of 10 (2
      to indefinite) years, continuing for an indefinite period in 33%. CONCLUSIONS:
      Most urologists use upper tract surveillance in patients with bladder cancer but
      there is wide variation in the duration and interval for which it continues, and
      in the type of patient selected for surveillance. Some patients at high risk of
      upper tract tumour are not being screened. Asymptomatic upper tract tumours may
      not be diagnosed because the intervals between surveillance are too long, and the
      duration for which it continues inadequate. There is a need for multidisciplinary
      national guidelines to reduce variation in practice.

PMID- 15476510
TI  - Salvage cystectomy after failure of interstitial radiotherapy and external beam
      radiotherapy for bladder cancer.
AB  - OBJECTIVE: To evaluate the long-term results of salvage cystectomy after
      interstitial radiotherapy (IRT) and external beam radiotherapy (EBRT) for
      transitional cell carcinoma, and to assess the morbidity and functional results
      of the different urinary diversions used. PATIENTS AND METHODS: The records of 27
      patients treated with salvage cystectomy in one institution between 1988 and 2003
      were retrospectively analysed. RESULTS: Salvage cystectomy was used after failure
      of IRT in 14 or EBRT in 13 patients, with a 3- and 5-year survival probability of
      46% (95% confidence interval 26-65) and 33 (11-54)%. The 5-year overall survival
      after cystectomy was 54% after IRT and 14% after EBRT (P = 0.12). Tumour
      category, response to radiation, American Society of Anesthesiology score, and
      complete tumour resection had a significant influence on survival. Five of seven
      patients with incomplete resection died because of local disease, with a median
      survival of 5 months. There was clinical understaging after radiotherapy in 41%
      of patients. Nine patients had an orthotopic neobladder, with complete day- and
      night-time continence in eight and four, respectively. All patients but one had
      good voiding function. There were early complications in two and late
      complications in six patients (for Bricker, seven of 14 and none; for Indiana,
      none of four and two of four). The duration of hospitalization was not influenced
      by the type of diversion. Erectile function was maintained in four of six
      patients after a sexuality-preserving cystectomy and neobladder. CONCLUSIONS:
      Salvage cystectomy can be performed with acceptable morbidity using any type of
      urinary diversion. Understaging after radiotherapy is common, but preoperative
      selection needs improving. A very significant factor for an adverse outcome and
      death from local tumour recurrence was incomplete resection, suggesting that
      salvage cystectomy should only be attempted if complete resection is probable.

PMID- 15476511
TI  - A comparison of the clinical outcome between open and hand-assisted laparoscopic
      nephroureterectomy for upper urinary tract transitional cell carcinoma.
AB  - OBJECTIVE: To report the surgical outcome of retroperitoneoscopic hand-assisted
      laparoscopic nephroureterectomy (LNU) with bladder cuff excision for upper
      urinary tract transitional cell carcinoma (TCC), and to compare the outcome with
      that of the open procedure (ONU). PATIENTS AND METHODS: From January 1998 to
      January 2003, 145 patients with upper urinary tract TCC were enrolled in the
      study; 87 had ONU and 58 retroperitoneoscopic hand-assisted LNU. The specimens
      were reviewed by experienced pathologists to confirm the pathological stage.
      Operative duration, intraoperative blood loss, bowel recovery, analgesic use,
      hospital stay and time to convalescence were compared for both groups. The Mann
      Whitney U-test and Fisher's exact test were used for statistical analysis.
      RESULTS The mean follow-up for ONU and LNU was 35.1 and 16.0 months, the mean
      operative duration 230.2 and 259.1 min (P = 0.006), the mean blood loss 747.3 and
      408.9 mL (P < 0.001), the mean duration of Foley catheterization 6.8 and 5.1 days
      (P < 0.001), and the hospital stay 12.6 and 9.3 days (P < 0.001). The bladder
      recurrence rate 2 years after surgery was 9.1% for ONU and 8.6% for LNU (P =
      0.23); the local recurrence rate during the follow-up was 3.4% and none,
      respectively (P = 0.35). CONCLUSION: Although LNU took longer than ONU the
      intraoperative bleeding and hospital stay were better than for ONU. Both
      procedures have statistically comparable bladder recurrence and local recurrence
      rates.

PMID- 15476512
TI  - Feasibility of radical perineal prostatectomy under spinal anaesthesia.
AB  - OBJECTIVE: To evaluate the possibility of a perineal radical prostatectomy (PRP)
      under spinal anaesthesia, as although it is usually done under general
      anaesthesia, there is currently a need to minimize costs and morbidity. PATIENTS
      AND METHODS: Between January and December 2003, there were 337 PRPs at our
      institution, of which 47 were on patients under combined spinal/epidural (CSE)
      anaesthesia administered via a standard L3/4 or L4/5 approach. We analysed the
      feasibility of PRP under CSE and evaluated perioperative morbidity, including
      blood loss and hospital stay. RESULTS: All 47 procedures were done under CSE with
      no need for conversion to general anaesthesia. The mean (range) duration of PRP
      was 56 (43-112) min, the mean blood loss 270 mL, and the transurethral catheter
      was removed at 7 days in 40 and at 14 days in the remaining seven patients. There
      were no complications during surgery, e.g. rectal or ureteric lesions. The mean
      hospital stay was 8.2 days. CONCLUSION: PRP is safe under CSE anaesthesia; this
      may be helpful in minimizing morbidity and medical costs, as well as providing an
      alternative in patients in whom general anaesthesia is not recommended.

PMID- 15476513
TI  - Permanent 125I-seed brachytherapy or radical prostatectomy: a prospective
      comparison considering oncological and quality of life results.
AB  - OBJECTIVE: To assess the quality of life in patients with prostate cancer after
      permanent brachytherapy (BT) or radical perineal prostatectomy (RP). PATIENTS AND
      METHODS: The American Brachytherapy Society recommends the permanent implantation
      of radioactive seeds as a monotherapy for patients with T1-T2aN0M0 prostate
      cancer and a prostate-specific antigen (PSA) level of < or = 10 ng/mL, a Gleason
      score of <7 and a prostate volume of <60 mL. Using these criteria, 132 patients
      with low-risk prostate cancer were selected; 52 had BT with 125I-seed
      implantation, 38 had RP with unilateral nerve-sparing (RP + NS) and 42 extended
      RP (RP group). Only patients with unilateral tumour on biopsy were considered.
      Before therapy and 6, 12 and 24 months afterward, patients completed
      questionnaires to assess perceived health and function. PSA relapse was diagnosed
      with a PSA of >0.1 ng/mL for patients in the RP groups, and three consecutive PSA
      increases for those after BT. RESULTS: Extraprostatic tumours were found in 18%
      of specimens taken during RP, and bilateral tumours in 63% of patients. After a
      mean follow-up of 27 months, there was PSA relapse in two of the 80 patients in
      the RP and RP + NS groups, and six of the 52 patients in the BT group; a
      significant difference, with a hazard ratio of 5.2. The acute morbidity was low
      in all groups. At 1 year, more than two incontinence pads were used by 5% of
      patients after RP and by 4% after BT. Similarly, at 1 year 15% of patients after
      RP and 13% after BT were bothered by urinary incontinence. Newly-developed fecal
      soiling was reported by 4%, 5% and 11% of the RP, RP + NS and BT groups
      respectively; none of the patients after RP and 4% after BT were bothered by this
      symptom. The duration and stiffness of erection was assessed after 1 year and
      reported to be equal or slightly decreased by a third after RP + NS and 38% after
      BT. Taking a 5-10 point difference as clinically relevant, role, emotional and
      social functioning were improved considerably after RP + NS than after BT, but
      sexual activity was impaired significantly after RP + NS than after BT.
      CONCLUSIONS: Both therapies showed typical acute and late morbidity; the most
      bothersome late symptoms were urinary incontinence for patients after RP and
      fecal soiling after BT. Sexual function was impaired significantly in patients
      who were potent before RP + NS, whereas after BT men reported only a minor change
      in sexual performance at 1 year. Tumour control after a median follow-up of 27
      months was better after RP but biochemical recurrence may still occur after > or
      = 5 years; therefore the present results are not mature enough and there were too
      few patients to provide a more definitive statement. As approximately 18% of
      patients considered to be appropriate candidates for BT had tumours extending
      beyond the prostate capsule or invading the seminal vesicles, nomograms are
      needed for more accurate information before therapy.

PMID- 15476514
TI  - The total percentage of biopsy cores with cancer improves the prediction of
      pathological stage after radical prostatectomy.
AB  - OBJECTIVE: To examine whether the simple variable 'percentage of cancer-positive
      biopsy cores' is a significant predictor of true pathological stage after radical
      prostatectomy and can be used to improve pathological stage prediction by simple
      means. PATIENTS AND METHODS: In all, 375 patients had a radical prostatectomy for
      localized prostate cancer in two UK centres; 260 had complete preoperative
      staging information. Logistic regression was used and predicted probability
      graphs constructed to assess predictors of pathological stage. RESULTS: In this
      study, only PSA (P = 0.004) and percentage cancer-positive biopsy cores (P <
      0.001) were significant predictors of pathological stage. The final model was an
      acceptable classifier for pathological stage (area under the receiver operating
      characteristic curve 0.76, specificity 85%, sensitivity 47%). A patient with a
      PSA of 10 ng/mL and one of six cores positive for cancer would have a predicted
      probability of extraprostatic disease of 20%, whereas the same patient with all
      six biopsy cores positive would have a predicted probability of extraprostatic
      disease of 80%. CONCLUSIONS: The percentage of cancer-positive biopsy cores
      significantly predicts the disease stage after radical prostatectomy. This
      variable is easy to obtain by the clinician and avoids the need to estimate the
      percentage of biopsy tissue infiltrated by cancer. This readily available
      information can easily be computed and may help to counsel patients about
      realistic expectations of organ-confined disease in relation to surgery as a
      treatment option.

PMID- 15476515
TI  - Comparison of doxazosin with or without tolterodine in men with symptomatic
      bladder outlet obstruction and an overactive bladder.
AB  - OBJECTIVE: To assess the efficacy of combined treatment with doxazosin and
      tolterodine, as although alpha-blockers are commonly used and generally effective
      in men with symptomatic bladder outlet obstruction (BOO), a subset of men with
      BOO and overactive bladder (OAB) symptoms often complain of persistent symptoms.
      PATIENTS AND METHODS: In a prospective study of 144 consecutive men with BOO at
      one tertiary urology centre, all had a baseline pressure-flow urodynamic study
      and were then subdivided into those with BOO or BOO + OAB, based on absence or
      presence of involuntary detrusor contractions. The Abrams-Griffiths nomogram was
      used to determine obstructive BOO. After the initial evaluation, all patients
      were treated with doxazosin 4 mg/day for 3 months. In patients with no
      symptomatic improvement, tolterodine 2 mg twice daily was added for an additional
      3 months. RESULTS: Of the 144 patients, 76 (53%) were diagnosed as having BOO and
      68 (47%) BOO + OAB. The patients with BOO + OAB were older (P < 0.05) and had a
      higher International Prostate Symptom Score. After 3 months of treatment with
      doxazosin, 60 (79%) with BOO and 24 (35%) BOO + OAB reported a symptomatic
      improvement. In those patients with no improvement, six of 16 with BOO and 32 of
      44 (73%) with BOO + OAB improved after adding tolterodine. Acute urinary
      retention developed in only two of 60 men (3.3%) treated with the combined
      therapy. CONCLUSION: About half of men with symptomatic BOO had an OAB; while
      about three-quarters of men with symptomatic BOO and no OAB improved with
      doxazosin, only a third with BOO + OAB were helped with doxazosin alone.
      Combining tolterodine with doxazosin was effective in three-quarters of men with
      BOO + OAB. Overall, most men with BOO with or with no OAB were helped with
      doxazosin alone or with the addition of tolterodine.

PMID- 15476516
TI  - Effect of controlled-release delivery on the pharmacokinetics of oxybutynin at
      different dosages: severity-dependent treatment of the overactive bladder.
AB  - OBJECTIVE: To assess the pharmacokinetics of a controlled-release formulation of
      oxybutynin (OROS-O, ALZA Corp., Mountain View, CA) at different dosages, compared
      with immediate-release oxybutynin (IR-O), and to determine the pharmacodynamic
      properties in the severity-dependent reduction of urge urinary incontinence
      (UUI). PATIENTS AND METHODS: In all, 105 patients were enrolled in this
      multicentre, randomized, double-blind study. Individual dose titration was used
      to assess the minimum effective, maximum tolerated or maximum allowed dose of
      either OROS-O or IR-O. Blood samples were collected during maintenance therapy
      with frequent sampling to analyse for R-oxybutynin and R-desethyloxybutynin
      concentrations. Pre-dose plasma levels before dosing were obtained as the minimum
      concentrations achieved at steady state during the dosing regimen. In parallel,
      UUI episodes were assessed at baseline and during maintenance therapy at the
      final dose level. RESULTS: For both IR-O and OROS-O, initial R-oxybutynin plasma
      concentrations increased in a dose-dependent fashion. For comparable dosages pre
      dose plasma levels were higher for OROS-O than IR-O. After one dose of IR-O
      plasma concentrations peaked at approximately 27-fold after 1 h and decreased to
      baseline levels within 4-8 h. In contrast, plasma concentrations of R-oxybutynin
      remained constant for up to 24 h after taking OROS-O at all doses. The overall
      percentage reduction in weekly UUI episodes was 84% (to 4.8 episodes) and 88% (to
      3.1 episodes) for OROS-O and IR-O, respectively (P < 0.05). Patients who titrated
      to final dose levels of 10, 15 and 20 mg OROS-O differed in their weekly UUI
      episodes at baseline (14.5, 30.3 and 42.0). Because of individual dose titration,
      UUI episodes/week were profoundly reduced at all applied doses (1.9-2.0,
      respectively). Fewer patients reported moderate to severe dry mouth with OROS-O
      than with IR-O (25% vs 46%, P < 0.05). CONCLUSION: The pharmacokinetics of OROS-O
      are proportional to dose, with minimal fluctuations between peak and trough
      concentrations, as associated with IR-O. In clinical practice OROS-O may thus
      facilitate the highly effective severity-dependent treatment of UUI with flexible
      dose adaptations based on the patients' needs.

PMID- 15476517
TI  - Virtual cystoscopy from computed tomography: a pilot study.
AB  - OBJECTIVE: To assess the feasibility of virtual cystoscopy reconstructed from
      helical computed tomography (CT) obtained using an intravenous contrast agent,
      and to correlate the findings with flexible (FC) and rigid cystoscopy (RC) in
      patients with bladder tumours. PATIENTS AND METHODS: Eighteen patients (16 men
      and two women, mean age 72 years, range 59-80) with haematuria and found to have
      a bladder tumour on FC were included in a pilot study. Contrast-enhanced helical
      CT scans were taken and based on these datasets, virtual cystoscopy (VC) images
      were reconstructed by a radiologist unaware of the findings at cystoscopy. All
      patients had RC and a biopsy taken. The VC images were compared with the findings
      from FC and RC. RESULTS: At FC, VC and RC, 32, 34 and 36 lesions were identified,
      respectively; 33 (92%) of the abnormal lesions at RC were correctly identified at
      VC. At VC, all lesions of >4 mm were identified but only one of three <4 mm was
      seen. There were two false-positive finding at VC; VC correctly identified 17
      (94%) of 18 abnormal bladders. Only 25% of the ureteric orifices were seen.
      Carcinoma in situ and urethral tumours were not visualized. CONCLUSION: CT-based
      VC has a high sensitivity for detecting bladder lesions and is comparable with
      FC; it may have a potential role as a single imaging tool for haematuria. Further
      larger studies are required to assess its clinical role.

PMID- 15476518
TI  - Intravenous urography-virtual cystoscopy is a better preliminary examination than
      air virtual cystoscopy.
AB  - OBJECTIVE: To describe a new technique of virtual cystoscopy (VC, used previously
      but with catheterization to drain residual urine and insufflation with air or
      carbon dioxide) with no invasive catheterization, used in parallel with
      intravenous urography (IVU), as conventional cystoscopy is an invasive but
      essential examination, and VC with multislice computed tomography (CT) was
      introduced to make preliminary examinations noninvasive. PATIENTS AND METHODS:
      Using multislice CT and a device with 16 rows of detectors, we examined five
      patients using VC that previously involved catheterization, termed 'air VC' and
      16 using VC with the new technique, termed 'IVU VC'. We assessed the new
      technique by evaluating the tumour detection rate, and merits and demerits of
      both types of VC. RESULTS: The detection rate of bladder tumours by IVU VC was
      similar to that from air VC; moreover, IVU VC overcame two significant
      disadvantages of air VC, i.e. the appearance of the water surface and the need
      for catheterization. CONCLUSION: Conventional cystoscopy is still an essential
      examination but this new method of IVU VC may be ideal for preliminary
      examination of the bladder.

PMID- 15476519
TI  - Development and validation of a quality-of-life scale for Chinese patients with
      benign prostatic hyperplasia.
AB  - OBJECTIVE: To develop and validate a quality of life (QoL) scale for Chinese
      patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: According
      to the QoL definition of the World Health Organisation, we adhered to the
      rigorous guidelines of instrument development to form a pool of items, selected
      items and validated the scale, using data from 256 patients with BPH. RESULTS: A
      74-item QoL scale for BPH (prior test version; BPH-QLS), including five domains
      (disease, physical, social, psychological, satisfaction) was developed and had
      good reliability and validity. The test-retest correlation coefficient and
      Cronbach's alpha coefficient of the BPH-QLS were 0.892 and 0.966. Thirteen common
      factors were extracted according to the conceptual model. The correlations of the
      BPH-QLS with the Short Form-36, the International Prostate Symptom Score (IPSS),
      and IPSS QoL score, and a published BPH-specific QoL scale were 0.784, 0.493,
      0.462 and 0.762, respectively. The BPH-QLS could be used to discriminate among
      patients with a different QoL. CONCLUSION: The new scale is reliable, valid and
      sensitive, and we recommend using the BPH-QLS in Chinese and Chinese-born
      patients worldwide to assist in clinical practice.

PMID- 15476520
TI  - The management of haemorrhagic cystitis with sodium pentosan polysulphate.
AB  - OBJECTIVE: To assess the use of sodium pentosan polysulphate (SPP) for
      haemorrhagic cystitis (HC), a potentially life-threatening side-effect in
      patients treated with pelvic radiotherapy or cyclophosphamide, and which can be
      difficult to manage as patients often have significant comorbidity. PATIENTS AND
      METHODS: Between September 1991 and December 2000, 60 consecutive patients (24
      women and 36 men) with haemorrhagic cystitis were primarily treated with SPP; 53
      patients had had radical radiotherapy for pelvic malignancy and seven systemic
      cyclophosphamide. All patients were screened for blood dyscrasia and
      residual/primary urothelial malignancy with imaging, urine cytology and
      cystoscopy. RESULTS: In all, 51 patients were available for follow-up; the median
      (range) interval between completing treatment and developing haematuria was 4.5
      (0.08-39.4) years, the duration of treatment 180 (21-1745) days and patients were
      followed for 450 (19-4526) days from the onset of haematuria. All patients were
      started on SPP at an initial dose of 100 mg three times daily. In 21 patients the
      dose was gradually reduced to a maintenance dose of 100 mg and in 10 further
      patients SPP was stopped because the haematuria stopped completely. Twenty
      patients died while on treatment from causes not directly related to their
      haematuria. CONCLUSION: We recommend the use of SPP as the primary method of
      managing haemorrhagic cystitis associated with pelvic radiotherapy or systemic
      chemotherapy.

PMID- 15476521
TI  - Upper pole access for complex lower pole renal calculi.
AB  - OBJECTIVES: To assess the efficacy of superior pole access for complex lower pole
      calyceal calculi. PATIENTS AND METHODS: In all, 102 patients with complex
      inferior calyceal calculi were included in a prospective unrandomized study.
      Complex inferior calyceal calculi were defined as multiple calculi in two or more
      inferior calyces of the lower polar group, with each calyx draining through a
      separate infundibulum and at an acute angle to each other. In 33 patients (32%;
      group 1) an inferior calyceal puncture was made and in 69 (68%; group 2) access
      was obtained through a superior calyceal puncture. The stone-free rates, decrease
      in haemoglobin, operative duration, requirement for additional tracts and second
      procedures in the two groups were compared. RESULTS: Stone clearance rates and
      blood loss values were better in group 2, although they were not significantly
      different. The mean operative duration, number of tracts required and the re-look
      procedure rate was significantly less in group 2. Two patients (3%) in group 2
      had hydrothorax related to supracostal puncture and required chest tube
      insertion. CONCLUSIONS: Superior calyceal puncture (supracostal or infracostal)
      affords optimum access to complex inferior calyceal stones, providing faster and
      better clearance with a single puncture, and less requirement for second-look
      procedures.

PMID- 15476522
TI  - An epidemiological study of renal pathology in tuberous sclerosis complex.
AB  - OBJECTIVES: To report the frequency of renal symptoms and complications of
      patients with tuberous sclerosis complex (TSC), to describe the ultrasonographic
      appearance of the kidneys in a population-based sample, and to investigate the
      relationship between a history of renal haemorrhage and renal lesions identified
      by ultrasonography. PATIENTS AND METHODS: As part of an epidemiological study,
      179 patients with TSC were identified as living in the Wessex Region in the South
      of England. Patients were interviewed and examined in their homes, to elicit the
      presence of renal symptoms or a history of renal complications. Renal
      ultrasonography was used in consenting patients in their homes. RESULTS: There
      was a history of renal complications in 16 (9%) patients; 149 consented to
      interview and examination, and 19 gave a history of renal symptoms in the
      previous year; 124 had renal ultrasonography; 86 (69%) had renal angiomyolipomas
      and 37 (30%) had renal cysts. Large lesions (>3 cm in diameter) were strongly
      associated with a history of symptomatic bleeding, although significant
      haemorrhage occurred in a 6-year-old child with small angiomyolipomas.
      CONCLUSIONS: The formation of angiomyolipoma in TSC is common. Polycystic kidney
      disease, renal carcinoma and renal failure, although rare, occur in TSC. Most
      patients with angiomyolipomas have neither complications nor symptoms. There was
      no appreciable difference between the sexes in the risk of developing these
      lesions. Although less commonly seen in the very young, there is no identifiable
      relationship after adolescence between age and the risk of having a renal
      angiomyolipoma. Bleeding tends to occur from large lesions (>3 cm) but most such
      patients have remained asymptomatic to date.

PMID- 15476523
TI  - In vitro assessment of decellularized porcine dermis as a matrix for urinary
      tract reconstruction.
AB  - OBJECTIVES: To assess the potential of Permacol (Tissue Science Laboratories,
      Swillington, UK), a natural matrix derived from decellularized porcine dermis, as
      a matrix for urological tissue engineering, and thus to develop an in vitro
      regimen for assessing the biocompatibility of potential biomaterials before
      experimentation in animal models. MATERIALS AND METHODS: Urinary tract-derived
      normal human urothelial (NHU) and smooth muscle (SM) cells were grown in
      monoculture as autologous cell lines. Permacol was assessed for its ability to
      support colonization by NHU and SM cells. The failure of the Permacol matrix to
      be infiltrated by SM cells was further investigated using the highly invasive EJ
      bladder cancer cell line. RESULTS: NHU cells readily attached and grew as a
      monolayer on the surface of Permacol. Cells stratified when the culture medium
      was supplemented with 2 mmol/L calcium. EJ cells initially grew on the surface
      and subsequently invaded the matrix, while SM cells only colonized the surface of
      Permacol when cocultured with NHU cells. Cytoxicity, evaluated by contact
      inhibition and conditioned-medium assays, excluded the presence of soluble toxins
      in the biomaterial. CONCLUSIONS: We developed a simple, reproducible and rigorous
      regimen for assessing potential biomaterials in vitro. Applying this system might
      reduce the use of animals and help to identify causes of potential bio
      incompatibility. The inability of SM cells to penetrate the Permacol matrix
      suggests that required matrix-bound signalling factors are absent, possibly as a
      result of the procedures used for processing Permacol. Identifying the key
      regulatory factors that regulate SM cell growth and orchestrate regenerative
      processes in the urinary tract will be important for developing suitable
      biomaterials for the bladder.

PMID- 15476524
TI  - Oral complications after buccal mucosal graft harvest for urethroplasty.
AB  - OBJECTIVE: To report long-term oral complications after buccal mucosal graft
      (BMG) harvesting for urethroplasty. PATIENTS AND METHODS: In a retrospective
      study of all patients who had BMG harvesting for urethroplasty from April 1996 to
      September 2002, telephone interviews were conducted using a standard proforma.
      RESULTS: Thirty-five patients were identified but only 30 (mean age 48.3 years,
      range 24-86) could be contacted; they had had 31 operations. Soon after surgery
      (the first 48 h), 22 (73%) of the patients had little or no oral pain; 70% and
      90% of the patients were able to eat and drink, respectively; 59% complained of
      numbness and 75% complained of tightness of the mouth. At discharge 6 days after
      surgery 90% of patients had little or no oral pain and all were able to eat and
      drink, but 10% had moderate-to-severe oral pain, 39% had oral numbness, and 52%
      had tightness of the mouth. At the time of interview, 16% of patients had oral
      numbness (mean duration 13.6 months) and 32% had tightness of the mouth (mean
      duration 20.9 months). In answer to the question of whether they would have their
      cheek mucosa harvested again if required, 74% responded 'yes', 3% 'no', and 23%
      had mixed feelings. CONCLUSIONS: BMG harvesting is a good operation, as most
      patients were satisfied, but it is not without long-term complications and
      patients should be adequately informed.

PMID- 15476525
TI  - Efficacy and safety of tadalafil in a Western European population of men with
      erectile dysfunction.
AB  - OBJECTIVE: To evaluate, in a randomized, double-blind, placebo-controlled,
      multicentre trial, the safety and efficacy of on-demand tadalafil (an oral
      phosphodiesterase type-5 inhibitor approved in many countries for treating
      erectile dysfunction, ED) in a Western European population of men with mild-to
      severe ED. PATIENTS AND METHODS: Patients were randomized according to baseline
      severity of ED in a ratio of 3 : 1 to receive either tadalafil 20 mg or placebo
      for 12 weeks. Primary efficacy endpoints were mean changes from baseline to
      endpoint (12 weeks) in the erectile function (EF) domain of the International
      Index of Erectile Function (IIEF) and percentages of 'Yes' responses to Sexual
      Encounter Profile (SEP) diary Question 2 ('Were you able to insert your penis
      into your partner's vagina?') and Question 3 ('Did your erection last long enough
      for you to have successful intercourse?'). Secondary endpoints included mean
      changes from baseline to endpoint in IIEF Intercourse Satisfaction and Overall
      Satisfaction domains, selected questions of the IIEF, and the percentage of 'Yes'
      responses to Global Assessment Questions (GAQ) at the last visit. Other analyses
      included the percentage of patients in each treatment group at endpoint with IIEF
      EF domain scores in the normal range (>26), the frequency of intercourse attempts
      and mean per-patient intercourse success rate at various times after dosing.
      RESULTS: The mean age of the patients was 53 years and 80% had a history of ED of
      > or = 1 year. The mean baseline EF domain score was 13.5, with 40.5% of patients
      in the severe category. Tadalafil improved mean EF domain scores by 11.1, vs 0.4
      for placebo (P < 0.001). In addition, 73.9% of sexual intercourse attempts were
      successful (SEP-Q3) in tadalafil-treated patients, compared with 29.9% in placebo
      treated patients during the period after baseline (P < 0.001). Tadalafil
      significantly improved the mean IIEF intercourse satisfaction (5.1, tadalafil;
      1.1, placebo) and overall satisfaction domain scores (3.9, tadalafil; 0.5,
      placebo), P < 0.001. GAQs used to assess the overall effect of the treatment
      indicated that tadalafil was superior to placebo (P < 0.001) in improving
      erections (82.1%, tadalafil; 23.1%, placebo) and sexual activity (78.6% and
      17.3%). The most common treatment-emergent adverse events more frequent (>2%)
      with tadalafil than placebo were headache, dyspepsia, flushing, back pain, pain
      in limb and myalgia. These adverse events were mostly mild to moderate.
      CONCLUSIONS: Tadalafil improved erectile function and was well tolerated when
      taken by men from Western Europe with mild-to-severe ED.

PMID- 15476526
TI  - Plaque incision and grafting as a salvage after a failed Nesbit procedure for
      Peyronie's disease.
AB  - OBJECTIVE: To analyse the outcome of plaque incision and grafting in patients who
      have a residual penile deformity after a Nesbit procedure for Peyronie's disease,
      as a further Nesbit procedure may present difficulties in dissection at the
      previous operative site, and may result in further penile shortening. PATIENTS
      AND METHODS: Over a 5-year period, 15 patients (mean age 58 years, range 34-66)
      presented with a residual penile deformity after a Nesbit procedure. All the
      patients had painless and stable Peyronie's disease. All patients had the
      Peyronie's plaque incised and grafted with either saphenous vein (12) or modified
      human fascia lata (three). The outcome was assessed using criteria which recorded
      the degree of penile shortening, quality of erections and penile angulation.
      RESULTS: Before surgery the mean (range) angle of deformity was 56 (40-90)
      degrees ; at a mean follow-up of 10 (3-16) months 11 patients had a straight
      penis, three a residual angle of 10-30 degrees and one had no change in angle.
      Two patients reported penile shortening and one a new onset of erectile
      dysfunction. Overall, 14 patients reported either an excellent or satisfactory
      result. CONCLUSIONS: These results indicate that plaque incision and grafting is
      an effective salvage operation to correct a residual penile deformity after a
      failed Nesbit procedure in patients with Peyronie's disease.

PMID- 15476527
TI  - Are published normal ranges of serum testosterone too high? Results of a cross
      sectional survey of serum testosterone and luteinizing hormone in healthy men.
AB  - OBJECTIVE: To derive normal ranges of serum testosterone and luteinizing hormone
      (LH) concentrations in healthy men, and thus evaluate whether testosterone
      replacement therapy is prescribed inappropriately. SUBJECTS AND METHOD: The study
      comprised 266 healthy male volunteers (aged 18-75 years) who were defined as
      healthy by strict eligibility criteria. Subjects had a body mass index (BMI) of
      18.6-32.2 kg/m2, smoked 0-10 cigarettes/day, and had an alcohol intake 0-40
      units/week (one unit = 8 g ethanol). We measured serum testosterone and LH
      concentrations in the morning (08.00-09.00 hours) and evening (20.00-21.00
      hours). RESULTS: Morning normal ranges of testosterone for men aged < or = 40
      years were 10.07-38.76 nmol/L (2.90-11.18 microg/L), and for men age > or = 40
      years, 7.41-24.13 (2.14-6.96); the respective evening normal ranges were 6.69
      31.51 (1.93-9.09) and 6.46-21.93 (1.86-6.33). Both morning and evening serum
      testosterone declined significantly with increasing age and BMI. LH was
      significantly higher in the morning than in the evening, but did not vary between
      the age groups or with BMI. The calculated normal ranges of LH were 0.9-7.0 IU/L
      (morning) and 0.7-6.8 IU/L (evening). CONCLUSIONS: The lower limit of normal for
      serum testosterone was 3-4 nmol/L (0.86-1.15 microg/L) lower than that of
      published ranges. The results have important implications for the diagnosis of
      hypogonadism and use of testosterone replacement therapy.

PMID- 15476528
TI  - Interpretation of the renogram: problems and pitfalls in hydronephrosis in
      children.
AB  - OBJECTIVE: To discuss the main steps of renographic technique and underline some
      pitfalls related to the acquisition, processing and interpretation of diuretic
      renography, an important method for guiding the management of asymptomatic
      congenital hydronephrosis. METHODS: Despite guidelines and consensus protocols,
      renographic procedures differ among centres, causing difficulties in comparison
      and controversy in the interpretation of results. Thus we comprehensively
      assessed published papers on the subject of diuretic renography. RESULTS:
      Differential renal function (DRF) is a robust measure provided there is adequate
      background subtraction. Pitfalls are related to the drawing of regions of
      interest, particularly in infants, to estimating the interval during which DRF is
      calculated, and to an adequate signal-to-noise ratio. There is no definition of a
      'significant' reduction in DRF. The classical variables of the diuretic renogram
      may not allow an estimate of the best drainage. Poor pelvic emptying may be
      apparent because the bladder is full and because the effect of gravity on
      drainage is incomplete. Estimating the drainage as residual activity rather than
      any parameter on the slope might be more adequate, especially if the time of
      frusemide administration is changed. Renal function and pelvic volume can
      influence the quality of drainage. Drainage may be better estimated using new
      tools. CONCLUSION: Provided the investigation is standardized and potential
      pitfalls accounted for, the diuretic renogram provides valuable and reproducible
      quantitative information on DRF and drainage.

PMID- 15476529
TI  - Sacral ratio and fecal continence in children with anorectal malformations.
AB  - OBJECTIVE: To evaluate the sacral ratio (SR) in patients with an anorectal
      malformation (ARM) and verify whether it has predictive value for fecal
      continence. PATIENT AND METHODS: From January 1990 to April 2002, 42 patients
      (aged 3-14 years) with an ARM and having already been operated on were reassessed
      and enrolled in the study. Patients with solid or paste-like stools but no
      soiling were deemed continent, those with similar stool and episodes of soiling
      partially continent, and those with no sphincter control, incontinent. The fecal
      continence was always analysed by the same observer. Sacral radiographic images
      were reviewed and the SR calculated from anteroposterior and images in the
      lateral position. All images were obtained before surgery and analysed by the
      same observer, while a third analysed the results. Results were considered
      statistically significant at P < 0.001. RESULTS: Seventeen patients were deemed
      continent, seven partially continent and 18 incontinent; there was no significant
      difference in SR among the three groups. When fecal continence was analysed in
      relation to changes in the findings on computed tomography of the lumbosacral
      spine, patients with sacral agenesis had a significantly higher frequency of
      fecal incontinence than the others, and all had a SR below 'normal'. CONCLUSION:
      Although the SR was different in patients with sacral agenesis it was no
      different in continent, partially continent or incontinent patients, and thus it
      is of no practical value in identifying patients likely to have fecal
      incontinence.

PMID- 15476530
TI  - Measurement of bladder compliance can be standardized by a dimensionless number:
      theoretical perspective.
AB  - OBJECTIVES: To: (i) calculate traditional compliance (CTrad) for a normal bladder
      by DeltaV/DeltaPdet, where DeltaV is the mean volumetric capacity and DeltaPdet
      is the detrusor pressure rise; (ii) assess its usefulness; (iii) identify the
      variables that are necessary for correctly assessing bladder compliance; and (iv)
      using these variables, report a method that, because it includes the effect of
      patient age, sex and size, correctly assesses compliance for management
      strategies. METHODS: We obtained the mean volumetric capacity of a normal bladder
      (V(cap,NL)) and the mean detrusor pressure rise (P(cap,NL)) on filling a normal
      bladder to its volumetric capacity from our and other published work; (ii)
      calculated CTrad for a normal bladder; (ii) showed that the variables necessary
      for assessing compliance correctly are DeltaV, DeltaPdet, V(cap,NL), and
      P(cap,NL); and (iii) showed that the relationship among these is the
      dimensionless number, NWahl(-1), calculated as
      (DeltaV/V(cap,NL))/(DeltaPdet/P(cap,NL)). This value for individuals with a
      normal bladder was calculated, tabulated and graphed. RESULTS: Because a normal
      individual's bladder capacity increases with age while the detrusor pressure
      increase does not, CTrad increases with age and therefore cannot be used for
      assessing compliance. Published data substantiate our result that CTrad for an
      individual with a normal bladder varies from 6.3 at 0.5 years old to 90 mL/cmH2O
      at 18 years old. NWahl(-1) correctly assesses bladder compliance because it is
      the same for all normal cases; consequently NWahl(-1) is more practical for
      clinical use. CONCLUSIONS: Bladder compliance is standardized using DeltaV,
      DeltaPdet, V(cap,NL), and P(cap,NL) to give NWahl(-1), and bladder compliance is
      usefully reported using this value.

PMID- 15476531
TI  - Measurement of bladder compliance can be standardized by a dimensionless number:
      clinical perspective.
AB  - OBJECTIVE: To devise a new, practical and more accurate method for measuring
      bladder compliance, and to show that traditional estimates of compliance are
      impractical. MATERIALS AND METHODS: Childhood bladder capacity varies greatly
      with age while detrusor pressure in a normal bladder does not. Consequently,
      traditional bladder compliance (DeltaV/DeltaP) increases with age, i.e.
      maturation. Therefore we devised a standard method that includes normal values of
      pressures and volumes to calculate and report bladder compliance in children, and
      that also applies to adults. A dimensionless number (NWahl(-1)) was computed for
      standardizing bladder compliance, comparing the normalized capacity to normalized
      pressure by the ratio (DeltaV/V(cap,NL))/(DeltaP/P(cap,NL)), where DeltaP is the
      pressure at bladder capacity, DeltaV the volume at bladder capacity, V(cap,NL)
      the volume at mean expected bladder capacity and P(cap,NL) the pressure at mean
      expected bladder capacity. V(cap,NL) is obtained from nomograms of published
      data. RESULTS: The bladder compliance of patients undergoing urodynamic testing
      was calculated using NWahl(-1) and the traditional equation (DeltaV/DeltaP).
      NWahl(-1) provided a more accurate diagnosis and therefore was of more practical
      use. CONCLUSIONS: Bladder compliance depends on patient age, sex and size; the
      new estimate used to standardize bladder compliance is based on these factors and
      is a dimensionless number. This may help when comparing patients and assessing
      outcomes.

PMID- 15476532
TI  - Detrusor pressure rise in a normal bladder.
AB  - OBJECTIVE: To determine the detrusor pressure rise of a normal bladder
      (P(cap,NL)) when filled to capacity. PATIENTS AND METHODS: Twenty-four patients
      with an apparently normal bladder, i.e. with symptoms but whose cystometrogram
      (CMG) showed no pathology of any kind and a near-normal pressure vs volume plot,
      were selected from 218 clinical CMGs. A straight line was fitted to the PV plot
      of these CMGs and then the P(cap,NL) calculated, e.g. by a straight line
      extending to the point of the normal expected cystometric bladder capacity
      (V(cap.NL)). Published data relative to P(cap,NL) were evaluated and compared
      with the values obtained. RESULTS: The mean (range) P(cap,NL) was 6 (4.5-7) cmH2O
      for patients with apparently normal bladders infused at the maximum physiological
      diuresis (MPD). This value was substantiated by three other studies of published
      values. The P(cap,NL) was 6 cmH2O at infusion rates of 10% of glomerular
      filtration rate (GFR), 10 cmH2O at 20% of GFR and 7-15 cmH2O for 3-10 times the
      infusion rate of 10% of GFR. CONCLUSION: P(cap,NL) is independent of age, size
      and sex and, at constant infusion rates of approximately MPD, will be 6. For
      infusion rates up to 35 mL/min, it is in the range of 6-15 cmH2O.

PMID- 15476533
TI  - The effect of neural embryonic stem cell therapy in a rat model of cavernosal
      nerve injury.
AB  - OBJECTIVE: To isolate embryonic stem cells that have differentiated along the
      neuronal cell line, and to assess whether injecting these neural stem cells into
      the corpus cavernosum influences cavernosal nerve regeneration and functional
      status. MATERIALS AND METHODS: Embryonic neural stem cells were obtained; 26 male
      Sprague-Dawley rats were divided into four groups: five had a sham operation;
      eight (controls) had a bilateral cavernosal nerve crush and injection of culture
      medium into the corpora cavernosa; four had an injection of neural embryonic stem
      (NES) cells into the major pelvic ganglion (MPG); and nine had bilateral
      cavernosal nerve crush and injection of NES cells into the corpora cavernosa.
      Erectile response was assessed by cavernosal nerve electrostimulation at 3
      months, and penile tissue samples were evaluated histochemically for nitric oxide
      synthase (NOS)-containing fibres, tyrosine hydroxylase and neurofilament
      staining. RESULTS: The groups injected with NES cells into the MPG and corpora
      cavernosa had significantly higher intracavernosal pressures than the control
      group. Immunohistochemical staining also revealed differences in the quality of
      the NOS-containing nerve fibres. Neurofilament staining was significantly better
      in the experimental groups injected with NES cells. CONCLUSION: We were able to
      isolate embryonic stem cells that had differentiated along the neural cell line
      and, using these NES cells intracavernosally, showed improved erectile function
      in a rat model of neurogenic impotence.

PMID- 15476534
TI  - Transmitters contributing to the voiding contraction in female rats.
AB  - OBJECTIVES: To assess in detail the contribution of acetylcholine and ATP to the
      different phases of the voiding contraction, urine flow and rhabdosphincter
      electromyographic (RB-EMG) activity in rats, using alpha,beta-methylene-ATP
      (desensitizing purinoceptors) and atropine (blocking muscarinic receptors). These
      agents and possibly other transmitters contribute to bladder emptying in rats,
      but how they contribute to the different phases of the micturition cycle,
      including the intraluminal pressure high-frequency oscillations (IPHFOs) is
      unclear. MATERIALS AND METHODS: Adult anaesthetized female Sprague-Dawley rats
      were used; intravesical pressure, RB-EMG and urine flow from the distal urethra
      were recorded. After baseline recordings, alpha,beta-methylene-ATP (0.5 mg/kg),
      atropine (1 mg/kg), or both, were injected intravenously. RESULTS: Alpha,beta
      Methylene-ATP significantly decreased the maximum bladder pressure during the
      first micturition phase, whereas atropine had little effect; the maximum bladder
      pressure during the second phase was also reduced. IPHFOs were apparent after
      both treatments. Atropine significantly reduced the maximum bladder pressure
      during the third phase. The maximum urinary flow rate was reduced by both
      alpha,beta-methylene-ATP and atropine; after exposure to both agents together,
      urinary flow was markedly reduced or stopped, and overflow incontinence
      developed. CONCLUSIONS: ATP contributes mainly to the initial and acetylcholine
      to the later phases of the voiding cycle in the rat. Neither agent abolished the
      IPHFOs; even after blocking the receptors for one transmitter and in the presence
      of IPHFOs, the bladder can still empty. However, if both receptors are blocked,
      overflow incontinence develops, suggesting that even if further transmitters are
      taking part in the voiding contraction, their physiological significance is
      questionable.

PMID- 15476535
TI  - Nerve growth factor and vanilloid receptor expression, and detrusor instability,
      after relieving bladder outlet obstruction in rats.
AB  - OBJECTIVE: To investigate mRNA expression for nerve growth factor (NGF) and
      vanilloid receptor TRPV1 in the bladder after relieving bladder outlet
      obstruction (BOO), and to correlate changes with functional changes of the
      bladder. MATERIALS AND METHODS: Temporary BOO was induced by partial urethral
      ligation in 40 male Wistar rats. After 3 weeks the obstruction was removed and
      the rats assessed by cystometry 3 weeks later. The bladder body of each rat was
      then removed, and NGF and TRPV1 mRNA expression measured by the reverse
      transcription-polymerase chain reaction. Fifteen sham-operated rats served as
      controls. RESULTS: Based on the cystometry, 10 of the 40 experimental rats were
      judged to have an unstable bladder, and the remaining 30 to have normal bladder
      function. The mean bladder weight in the normal and unstable groups was higher
      than in the control group, and there was no significant difference between the
      normal and unstable groups. The bladder contraction pressure was similar in the
      three groups but the mean contraction interval was markedly shorter in the
      unstable than in the control and normal groups (P < 0.05). The mRNA expressions
      of NGF and TRPV1 were higher in the unstable than in the control and normal
      groups. CONCLUSIONS: NGF and TRPV1 were apparently increased in unstable bladder
      tissue after relieving BOO; these changes may be related to irritative symptoms
      after correcting BOO.

PMID- 15476536
TI  - Quantitative morphometric analysis of individual resected prostatic tissue
      specimens, using immunohistochemical staining and colour-image analysis.
AB  - OBJECTIVE: To develop a method for obtaining morphometric measurements
      representative of individual chips from transurethral resection of the prostate
      (TURP). MATERIALS AND METHODS: In all, 232 sections were cut in pairs from 25
      TURP chips, collected from four patients undergoing TURP for benign prostatic
      hyperplasia. Individual tissue chips were processed, embedded in paraffin wax and
      pairs of neighbouring sections cut from the specimens at intervals of 300 microm
      throughout the thickness of the specimen. Of each pair, the epithelial tissue
      (ET) of one and the smooth muscle (SM) of the other section were stained
      immunohistochemically with anti-prostate-specific antigen and anti-SM myosin,
      respectively. Proportions of ET and SM within the sections were measured with
      colour-image analysis and calculated within the TURP chips using all pairs of
      sections cut from the specimen, and the first pair of sections only. The
      differences between the sets of results were analysed using descriptive
      statistics. RESULTS: From each TURP chip, 3-7 pairs of sections were cut; for
      both ET and SM within each chip the differences between the results calculated
      using data from all pairs of sections and the first pair alone were small, as
      were the distributions of these differences within each prostate. CONCLUSIONS:
      Morphometric measurements from one section from a processed TURP chip, as opposed
      to serial sections, can be used to reliably assess the morphology of tissue
      within that specimen. This permits a considerable saving of resources when
      undertaking morphometric image analysis of resected prostatic tissue specimens.

PMID- 15476537
TI  - Induction of proliferation and differentiation of cultured urothelial cells on
      acellular biomaterials.
AB  - OBJECTIVE: To determine the optimum conditions for the proliferation of
      urothelial cells, leading to the confluent coverage of large surfaces of
      biocompatible membranes, and for their terminal differentiation. MATERIALS AND
      METHODS: Porcine and human urothelial cells were cultured on different matrices
      under different growth conditions. Proliferative activity and the viability of
      cells were evaluated using fluorescent markers for nuclei and cytoplasm. Growth
      and differentiation were assessed by histological, histochemical and
      immunohistochemical methods. RESULTS: Under fibroblastic induction and
      supplementation of 5% fetal calf serum (FCS), urothelial cells showed more
      proliferation than in other conditions tested. Terminal differentiation of
      superficial cells was achieved by lowering the concentration of FCS to 1% at the
      air-liquid interface. CONCLUSIONS: The mitogenic effects of the extracellular
      matrix content of biological membranes and fibroblastic inductive factors are
      synergistic with each other, and can compensate for a low FCS concentration and
      the absence of other additives. Lowering the FCS concentration to 1% inhibits the
      proliferation of urothelial cells and permits their terminal differentiation.

PMID- 15476538
TI  - The final dose of clinical trial designs.

PMID- 15476539
TI  - Holmium laser-enucleation of the prostate enables early catheter removal.

PMID- 15476540
TI  - Colposcopy in the diagnosis of infrasphincteric ureteric ectopia.

PMID- 15476544
TI  - Genes differentially expressed in prostate cancer.

PMID- 15476545
TI  - Renal trauma: indications for imaging and surgical exploration. A point of
      clarification.

PMID- 15476546
TI  - Ten years' experience of retrograde balloon dilatation of pelvi-ureteric junction
      obstruction.

PMID- 15476547
TI  - A model to explain the 'vanishing' prostate -- the curative biopsy theory.

PMID- 15476550
TI  - Medical writing.

PMID- 15476551
TI  - Modified retroperitoneal lymphadenectomy.

PMID- 15476554
TI  - Identification of endogenous retroviral reading frames in the human genome.
AB  - BACKGROUND: Human endogenous retroviruses (HERVs) comprise a large class of
      repetitive retroelements. Most HERVs are ancient and invaded our genome at least
      25 million years ago, except for the evolutionary young HERV-K group. The far
      majority of the encoded genes are degenerate due to mutational decay and only a
      few non-HERV-K loci are known to retain intact reading frames. Additional intact
      HERV genes may exist, since retroviral reading frames have not been
      systematically annotated on a genome-wide scale. RESULTS: By clustering of hits
      from multiple BLAST searches using known retroviral sequences we have mapped 1.1%
      of the human genome as retrovirus related. The coding potential of all identified
      HERV regions were analyzed by annotating viral open reading frames (vORFs) and we
      report 7836 loci as verified by protein homology criteria. Among 59 intact or
      almost-intact viral polyproteins scattered around the human genome we have found
      29 envelope genes including two novel gammaretroviral types. One encodes a
      protein similar to a recently discovered zebrafish retrovirus (ZFERV) while
      another shows partial, C-terminal, homology to Syncytin (HERV-W/FRD).
      CONCLUSIONS: This compilation of HERV sequences and their coding potential
      provide a useful tool for pursuing functional analysis such as RNA expression
      profiling and effects of viral proteins, which may, in turn, reveal a role for
      HERVs in human health and disease. All data are publicly available through a
      database at http://www.retrosearch.dk.

PMID- 15476555
TI  - Characterization of an endogenous retrovirus class in elephants and their
      relatives.
AB  - BACKGROUND: Endogenous retrovirus-like elements (ERV-Ls, primed with tRNA
      leucine) are a diverse group of reiterated sequences related to foamy viruses and
      widely distributed among mammals. As shown in previous investigations, in many
      primates and rodents this class of elements has remained transpositionally
      active, as reflected by increased copy number and high sequence diversity within
      and among taxa. RESULTS: Here we examine whether proviral-like sequences may be
      suitable molecular probes for investigating the phylogeny of groups known to have
      high element diversity. As a test we characterized ERV-Ls occurring in a sample
      of extant members of superorder Uranotheria (Asian and African elephants,
      manatees, and hyraxes). The ERV-L complement in this group is even more diverse
      than previously suspected, and there is sequence evidence for active expansion,
      particularly in elephantids. Many of the elements characterized have protein
      coding potential suggestive of activity. CONCLUSIONS: In general, the evidence
      supports the hypothesis that the complement had a single origin within basal
      Uranotheria.

PMID- 15476556
TI  - Description and evaluation of an EBM curriculum using a block rotation.
AB  - BACKGROUND: While previous authors have emphasized the importance of integrating
      and reinforcing evidence-based medicine (EBM) skills in residency, there are few
      published examples of such curricula. We designed an EBM curriculum to train
      family practice interns in essential EBM skills for information mastery using
      clinical questions generated by the family practice inpatient service. We sought
      to evaluate the impact of this curriculum on interns, residents, and faculty.
      METHODS: Interns (n = 13) were asked to self-assess their level of confidence in
      basic EBM skills before and after their 2-week EBM rotation. Residents (n = 21)
      and faculty (n = 12) were asked to assess how often the answers provided by the
      EBM intern to the inpatient service changed medical care. In addition, residents
      were asked to report how often they used their EBM skills and how often EBM
      concepts and tools were used in teaching by senior residents and faculty. Faculty
      were asked if the EBM curriculum had increased their use of EBM in practice and
      in teaching. RESULTS: Interns significantly increased their confidence over the
      course of the rotation. Residents and faculty felt that the answers provided by
      the EBM intern provided useful information and led to changes in patient care.
      Faculty reported incorporating EBM into their teaching (92%) and practice (75%).
      Residents reported applying the EBM skills they learned to patient care (86%) and
      that these skills were reinforced in the teaching they received outside of the
      rotation (81%). All residents and 11 of 12 faculty felt that the EBM curriculum
      had improved patient care. CONCLUSIONS: To our knowledge, this is the first
      published EBM curriculum using an individual block rotation format. As such, it
      may provide an alternative model for teaching and incorporating EBM into a
      residency program.

PMID- 15476557
TI  - A CpG island hypermethylation profile of primary colorectal carcinomas and colon
      cancer cell lines.
AB  - BACKGROUND: Tumor cell lines are commonly used as experimental tools in cancer
      research, but their relevance for the in vivo situation is debated. In a series
      of 11 microsatellite stable (MSS) and 9 microsatellite unstable (MSI) colon
      cancer cell lines and primary colon carcinomas (25 MSS and 28 MSI) with known
      ploidy stem line and APC, KRAS, and TP53 mutation status, we analyzed the
      promoter methylation of the following genes: hMLH1, MGMT, p16INK4a (CDKN2A alpha
      transcript), p14ARF (CDKN2A beta-transcript), APC, and E-cadherin (CDH1). We
      compared the DNA methylation profiles of the cell lines with those of the primary
      tumors. Finally, we examined if the epigenetic changes were associated with known
      genetic markers and/or clinicopathological variables. RESULTS: The cell lines and
      primary tumors generally showed similar overall distribution and frequencies of
      gene methylation. Among the cell lines, 15%, 50%, 75%, 65%, 20% and 15% showed
      promoter methylation for hMLH1, MGMT, p16INK4a, p14ARF, APC, and E-cadherin,
      respectively, whereas 21%, 40%, 32%, 38%, 32%, and 40% of the primary tumors were
      methylated for the same genes. hMLH1 and p14ARF were significantly more often
      methylated in MSI than in MSS primary tumors, whereas the remaining four genes
      showed similar methylation frequencies in the two groups. Methylation of p14ARF,
      which indirectly inactivates TP53, was seen more frequently in tumors with normal
      TP53 than in mutated samples, but the difference was not statistically
      significant. Methylation of p14ARF and p16INK4a was often present in the same
      primary tumors, but association to diploidy, MSI, right-sided location and female
      gender was only significant for p14ARF. E-cadherin was methylated in 14/34 tumors
      with altered APC further stimulating WNT signaling. CONCLUSIONS: The present
      study shows that colon cancer cell lines are in general relevant in vitro models,
      comparable with the in vivo situation, as the cell lines display many of the same
      molecular alterations as do the primary carcinomas. The combined pattern of
      epigenetic and genetic aberrations in the primary carcinomas reveals associations
      between them as well as to clinicopathological variables, and may aid in the
      future molecular assisted classification of clinically distinct stages.

PMID- 15476558
TI  - Rank Difference Analysis of Microarrays (RDAM), a novel approach to statistical
      analysis of microarray expression profiling data.
AB  - BACKGROUND: A key step in the analysis of microarray expression profiling data is
      the identification of genes that display statistically significant changes in
      expression signals between two biological conditions. RESULTS: We describe a new
      method, Rank Difference Analysis of Microarrays (RDAM), which estimates the total
      number of truly varying genes and assigns a p-value to each signal variation.
      Information on a group of differentially expressed genes includes the sensitivity
      and the false discovery rate. We demonstrate the feasibility and efficiency of
      our approach by applying it to a large synthetic expression data set and to a
      biological data set obtained by comparing vegetatively-growing wild type and tor2
      mutant yeast strains. In both cases we observed a significant improvement of the
      power of analysis when our method is compared to another popular nonparametric
      method. CONCLUSIONS: This study provided a valuable new statistical method to
      analyze microarray data. We conclude that the good quality of the results
      obtained by RDAM is mainly due to the quasi-perfect equalization of variation
      distribution, which is related to the standardization procedure used and to the
      measurement of variation by rank difference.

PMID- 15476559
TI  - Surveillance of antimicrobial resistance at a tertiary hospital in Tanzania.
AB  - BACKGROUND: Antimicrobial resistance is particularly harmful to infectious
      disease management in low-income countries since expensive second-line drugs are
      not readily available. The objective of this study was to implement and evaluate
      a computerized system for surveillance of antimicrobial resistance at a tertiary
      hospital in Tanzania. METHODS: A computerized surveillance system for
      antimicrobial susceptibility (WHONET) was implemented at the national referral
      hospital in Tanzania in 1998. The antimicrobial susceptibilities of all clinical
      bacterial isolates received during an 18 months' period were recorded and
      analyzed. RESULTS: The surveillance system was successfully implemented at the
      hospital. This activity increased the focus on antimicrobial resistance issues
      and on laboratory quality assurance issues. The study identified specific
      nosocomial problems in the hospital and led to the initiation of other
      prospective studies on prevalence and antimicrobial susceptibility of bacterial
      infections. Furthermore, the study provided useful data on antimicrobial patterns
      in bacterial isolates from the hospital. Gram-negative bacteria displayed high
      rates of resistance to common inexpensive antibiotics such as ampicillin,
      tetracycline and trimethoprim-sulfamethoxazole, leaving fluoroquinolones as the
      only reliable oral drugs against common Gram-negative bacilli. Gentamicin and
      third generation cephalosporins remain useful for parenteral therapy. CONCLUSION:
      The surveillance system is a low-cost tool to generate valuable information on
      antimicrobial resistance, which can be used to prepare locally applicable
      recommendations on antimicrobial use. The system pinpoints relevant nosocomial
      problems and can be used to efficiently plan further research. The surveillance
      system also functions as a quality assurance tool, bringing attention to
      methodological issues in identification and susceptibility testing.

PMID- 15476560
TI  - Evolutionary relationships of Aurora kinases: implications for model organism
      studies and the development of anti-cancer drugs.
AB  - BACKGROUND: As key regulators of mitotic chromosome segregation, the Aurora
      family of serine/threonine kinases play an important role in cell division.
      Abnormalities in Aurora kinases have been strongly linked with cancer, which has
      lead to the recent development of new classes of anti-cancer drugs that
      specifically target the ATP-binding domain of these kinases. From an evolutionary
      perspective, the species distribution of the Aurora kinase family is complex.
      Mammals uniquely have three Aurora kinases, Aurora-A, Aurora-B, and Aurora-C,
      while for other metazoans, including the frog, fruitfly and nematode, only Aurora
      A and Aurora-B kinases are known. The fungi have a single Aurora-like homolog.
      Based on the tacit assumption of orthology to human counterparts, model organism
      studies have been central to the functional characterization of Aurora kinases.
      However, the ortholog and paralog relationships of these kinases across various
      species have not been rigorously examined. Here, we present comprehensive
      evolutionary analyses of the Aurora kinase family. RESULTS: Phylogenetic trees
      suggest that all three vertebrate Auroras evolved from a single urochordate
      ancestor. Specifically, Aurora-A is an orthologous lineage in cold-blooded
      vertebrates and mammals, while structurally similar Aurora-B and Aurora-C evolved
      more recently in mammals from a duplication of an ancestral Aurora-B/C gene found
      in cold-blooded vertebrates. All so-called Aurora-A and Aurora-B kinases of non
      chordates are ancestral to the clade of chordate Auroras and, therefore, are not
      strictly orthologous to vertebrate counterparts. Comparisons of human Aurora-B
      and Aurora-C sequences to the resolved 3D structure of human Aurora-A lends
      further support to the evolutionary scenario that vertebrate Aurora-B and Aurora
      C are closely related paralogs. Of the 26 residues lining the ATP-binding active
      site, only three were variant and all were specific to Aurora-A. CONCLUSIONS: In
      this study, we found that invertebrate Aurora-A and Aurora-B kinases are highly
      divergent protein families from their chordate counterparts. Furthermore, while
      the Aurora-A family is ubiquitous among all vertebrates, the Aurora-B and Aurora
      C families in humans arose from a gene duplication event in mammals. These
      findings show the importance of understanding evolutionary relationships in the
      interpretation and transference of knowledge from studies of model organism
      systems to human cellular biology. In addition, given the important role of
      Aurora kinases in cancer, evolutionary analysis and comparisons of ATP-binding
      domains suggest a rationale for designing dual action anti-tumor drugs that
      inhibit both Aurora-B and Aurora-C kinases.

PMID- 15476561
TI  - The prevalence and severity of oral impacts on daily performances in Thai primary
      school children.
AB  - BACKGROUND: Traditional methods of measuring oral health mainly use clinical
      dental indices and have been complemented by oral health related quality of life
      (OHRQoL) measures. Most OHRQoL studies have been on adults and elderly
      populations. There are no systematic OHRQoL studies of a population-based sample
      of children. The objective of this study was to assess the prevalence,
      characteristics and severity of oral impacts in primary school children. METHODS:
      Cross-sectional study of all 1126 children aged 11-12 years in a municipal area
      of Suphanburi province, Thailand. An OHRQoL measure, Child-Oral Impacts on Daily
      Performances index (Child-OIDP) was used to assess oral impacts. Children were
      also clinically examined and completed a self-administered questionnaire about
      demographic information and oral behaviours. RESULTS: 89.8% of children had one
      or more oral impacts. The median impact score was 7.6 and mean score was 8.8.
      Nearly half (47.0%) of the children with impacts had impacts at very little or
      little levels of intensity. Most (84.8%) of those with impacts had 1-4 daily
      performances affected (out of 8 performances). Eating was the most common
      performance affected (72.9%). The severity of impacts was high for eating and
      smiling and low for study and social contact performances. The main clinical
      causes of impacts were sensitive tooth (27.9%), oral ulcers (25.8%), toothache
      (25.1%) and an exfoliating primary tooth (23.4%). CONCLUSIONS: The study reveals
      that oral health impacts on quality of life in Thai primary school children. Oral
      impacts were prevalent, but not severe. The impacts mainly related to difficulty
      eating and smiling. Toothache, oral ulcers and natural processes contributed
      largely to the incidence of oral impacts.

PMID- 15476562
TI  - Lack of association between vascular dementia and Chlamydia pneumoniae infection:
      a case-control study.
AB  - BACKGROUND: Chronic inflammation appears to play a role in the pathogenesis of
      vascular dementia. Given the association between Chlamydia pneumoniae and stroke,
      the possibility exists that previous exposure to C. pneumoniae may play a role in
      vascular dementia. The objective of this study was to determine if there was an
      association between serological evidence of C. pneumoniae infection or
      inflammatory markers with vascular dementia. METHODS: 28 case-patients with
      vascular dementia at a geriatric clinic and 24 caregiver-controls were tested for
      C. pneumoniae IgG and IgA antibodies. The association between vascular dementia
      and C. pneumoniae titres as well as inflammatory markers was estimated by using
      both conditional logistic regression and stratified logistic regression. RESULTS:
      When matched cases were compared to controls, there was no significant difference
      in elevated C. pneumoniae specific IgG antibodies (titre >or= 1:32), odds ratio
      [OR] 1.3 (95% confidence intervals [CI] 0.3 to 6.0), p = 0.71, or in elevated C.
      pneumoniae specific IgA antibodies (titre >or= 1:16), OR 2.0 (95%CI 0.5 to 8.0),
      p = 0.33 indicative of past or persistent C. pneumoniae infection. Similarly, no
      difference in high IgG or IgA antibody levels (IgG titre >or= 1:512 or IgA titre
      >or= 1:64) between the two groups, indicative of recent C. pneumoniae infection,
      was found, OR 0.4 (95%CI 0.1 to 2.1), p = 0.27. For C-reactive protein (CRP), the
      mean difference between 18 matched pairs (case - control) was - 3.33 mg/L. There
      was no significant difference between cases and controls when comparing log
      transformed values, OR 0.03 (95%CI 0.00 to 2.89), p = 0.13 or comparing CRP
      values above or below the median, OR 0.8 (95%CI 0.2 to 3.4), p = 0.71. For
      fibrinogen, the mean difference between pairs (case - control) was -0.07 g/L.
      There was no statistical difference between cases and controls when comparing log
      transformed values, OR 0.6 (95%CI 0.0 to 31.2), p = 0.79 or between fibrinogen
      values above and below the median, OR = 0.5 (95%CI 0.1 to 2.0), p = 0.50.
      CONCLUSION: We found no evidence for a significant association between C.
      pneumoniae infection, inflammatory markers such as CRP and fibrinogen, and
      vascular dementia.

PMID- 15476563
TI  - Length of sick leave - why not ask the sick-listed? Sick-listed individuals
      predict their length of sick leave more accurately than professionals.
AB  - BACKGROUND: The knowledge of factors accurately predicting the long lasting sick
      leaves is sparse, but information on medical condition is believed to be
      necessary to identify persons at risk. Based on the current practice, with
      identifying sick-listed individuals at risk of long-lasting sick leaves, the
      objectives of this study were to inquire the diagnostic accuracy of length of
      sick leaves predicted in the Norwegian National Insurance Offices, and to compare
      their predictions with the self-predictions of the sick-listed. METHODS: Based on
      medical certificates, two National Insurance medical consultants and two National
      Insurance officers predicted, at day 14, the length of sick leave in 993
      consecutive cases of sick leave, resulting from musculoskeletal or mental
      disorders, in this 1-year follow-up study. Two months later they reassessed 322
      cases based on extended medical certificates. Self-predictions were obtained in
      152 sick-listed subjects when their sick leave passed 14 days. Diagnostic
      accuracy of the predictions was analysed by ROC area, sensitivity, specificity,
      likelihood ratio, and positive predictive value was included in the analyses of
      predictive validity. RESULTS: The sick-listed identified sick leave lasting 12
      weeks or longer with an ROC area of 80.9% (95% CI 73.7-86.8), while the
      corresponding estimates for medical consultants and officers had ROC areas of
      55.6% (95% CI 45.6-65.6%) and 56.0% (95% CI 46.6-65.4%), respectively. The
      predictions of sick-listed males were significantly better than those of female
      subjects, and older subjects predicted somewhat better than younger subjects.
      Neither formal medical competence, nor additional medical information, noticeably
      improved the diagnostic accuracy based on medical certificates. CONCLUSION: This
      study demonstrates that the accuracy of a prognosis based on medical
      documentation in sickness absence forms, is lower than that of one based on
      direct communication with the sick-listed themselves.

PMID- 15476564
TI  - A narrow complex tachycardia in a man with palpitations for many years.

PMID- 15476565
TI  - Hormone therapy and selective estrogen receptor modulators for prevention of
      coronary heart disease in postmenopausal women estrogen replacement from the
      cardiologist's perspective.
AB  - Coronary heart disease is the leading cause of morbidity and mortality in women
      older than the age of 50 in the United States today. Traditional cardiovascular
      risk factors (hyperlipidemia, glucose intolerance, and hypertension) are more
      clearly associated with significant cardiovascular risk after menopause. The
      increased incidence of cardiovascular events in postmenopausal women and the
      evidence that cardiovascular disease on average manifests a decade later in women
      compared with men suggests that estrogen deficiency may predispose women to a
      higher cardiovascular risk. Numerous biologic mechanisms have been proposed that
      relate use of hormone therapy (HT) to improved lipid profiles, insulin
      sensitivity, and vascular reactivity. Early observational trials in the last 2
      decades showed a significant decrease in cardiovascular events. Recently
      published randomized clinical trial results, however, have led to uncertainty
      about the earlier established cardiovascular benefits of HT. To complicate issues
      further, alternative estrogenlike compounds, selective estrogen receptor
      modulators, are being introduced that appear to convey similar cardiovascular
      benefit and notably less cancer risk than HT. The newly released randomized
      trials on hormone and nonhormonal agents are reviewed.

PMID- 15476566
TI  - Reversible pulmonary hypertension, tricuspid regurgitation and right-sided heart
      failure associated with hyperthyroidism: case report and review of the
      literature.
AB  - Primary pulmonary hypertension carries a grim prognosis, therefore, it is
      imperative that prior to reaching this diagnosis, a thorough search be made for
      all possible causes of pulmonary hypertension. An uncommon cause of pulmonary
      hypertension amenable to treatment may occasionally be identified. This case
      report describes a young woman who presented with rapidly progressive right heart
      failure. Work up for the common secondary causes of pulmonary hypertension was
      negative, including, congenital intracardiac shunts, left-sided atrial or
      ventricular heart disease, left-sided valvular heart disease, disorders of the
      respiratory system including hypoxemia and pulmonary thromboembolic and
      venoocclusive disease, collagen vascular disease, portal hypertension, HIV
      infection as well as pulmonary hypertension secondary to drugs and toxins. The
      only concurrent illness identified was Graves disease. After treatment of
      hyperthyroidism there was complete resolution of the right heart failure,
      tricuspid regurgitation, and the pulmonary hypertension. Only a few cases of
      reversible pulmonary hypertension and right heart failure associated with
      hyperthyroidism have been reported worldwide. In these patients, the most
      striking feature has been the normalization of the cardiovascular findings after
      adequate treatment of hyperthyroidism. The exact reasons for the development of
      pulmonary hypertension in hyperthyroidism are unclear. Proposed mechanisms
      include high cardiac output-induced endothelial injury, increased metabolism of
      intrinsic pulmonary vasodilating substances resulting in elevated pulmonary
      vascular resistance, and autoimmune phenomenon. Hyperthyroidism should be
      included in the causes of secondary pulmonary hypertension and/or otherwise
      unexplained right heart failure. This is especially important because
      hyperthyroidism is a treatable entity and its cardiac manifestations may be
      completely reversible.

PMID- 15476567
TI  - A case of massive dystrophic cardiac calcinosis with increased bone resorption
      markers: a novel pathophysiologic link?
AB  - We report a 72-year-old man who presented to our emergency room with congestive
      heart failure that was resistant to initial medical therapy. He had suffered from
      anterior myocardial infarction 20 years prior. Echocardiography and computed
      tomography revealed marked cardiac calcification including myocardium, chordal
      structures, mitral annulus, and aortic valve. Neither chronic renal insufficiency
      nor hypercalcemia were present in our patient. Bone resorption markers were
      increased and bone mineral density was consistent with severe osteoporosis. We
      suggested a novel mechanism, that increased bone resorption may lead to
      accumulation of calcium into avascular tissues in the heart (ie, chordal
      structures, mitral annulus, aortic valve, and fibronecrotic myocardium)
      especially in the setting of high left ventricular end-diastolic pressure.
      Dystrophic cardiac calcinosis, an age-related cardiomyopathy, is associated with
      elevated bone resorption markers and it may cause alterations in cellular calcium
      hemostasis with initiation of deleterious events leading to aggravate dilated and
      restrictive cardiomyopathy and may result in intractable congestive heart
      failure. The implication of this case report needs to be reemphasized.

PMID- 15476568
TI  - Myocardial perfusion imaging in acute coronary syndromes: potential use in
      decision making for emergent revascularization.
AB  - We report two cases of patients presenting to the emergency department with chest
      pain who had low risk electrocardiographic findings. Myocardial perfusion imaging
      (MPI) revealed a significant area of decreased uptake suggestive of acute
      transmural infarction. In both cases, biochemical markers later confirmed the
      diagnosis of myocardial infarction. Cardiac catheterization revealed a large area
      at risk which was then treated with percutaneous intervention. As MPI is
      increasingly utilized in the acute evaluation of chest pain, it may serve as a
      useful adjunct in selecting patients who may benefit from emergent cathertization
      and revascularization.

PMID- 15476570
TI  - Sauna as a therapeutic option for cardiovascular disease.
AB  - The physiologic effect of the sauna in human beings has been studied extensively,
      but only recently have there been studies to suggest sauna can be an effective
      therapeutic modality for patients with cardiovascular disease, especially for
      those with congestive heart failure. The data reported to date have been
      promising, but definitive studies are not possible because sauna treatment would
      be difficult to evaluate in a double-blind, placebo-controlled study.

PMID- 15476569
TI  - Constrictive pericarditis versus restrictive cardiomyopathy: challenges in
      diagnosis and management.
AB  - This is the case of a patient who presented with severe right-sided heart failure
      due to diastolic dysfunction that caused a dilemma of differential diagnosis
      between restrictive cardiomyopathy and constrictive pericarditis. Restrictive
      cardiomyopathy was diagnosed based on noninvasive and invasive hemodynamic
      testing. However, the patient did not respond to therapy and succumbed to
      worsening heart failure and multiple comorbidities. Clinical features of right
      heart failure with edema, ascites, jugular venous distention, and tender
      hepatomegaly are commonly seen in clinical practice. When systolic function is
      determined to be normal, diastolic causes of heart failure must be ruled out.
      These include myocardial disorders with a broad range of pathologies leading to
      restrictive physiology, of which amyloidosis is a prototype. Pericardial
      disorders leading to diastolic heart failure are usually in the form of
      constrictive physiology, when pericardial tamponade is ruled out. Differentiation
      between restrictive and constrictive pathologies is often difficult and requires
      careful attention to hemodynamic and Doppler echocardiographic features. We
      report a case of severe right heart failure illustrating some of the complexities
      in decision-making and the importance of meticulous hemodynamic and ancillary
      testing in the diagnosis and treatment of this often fatal condition.

PMID- 15476571
TI  - Septic thrombophlebitis of the coronary sinus with complete recovery after
      surgical intervention.
AB  - This case represents a unique presentation of septic thrombophlebitis of the
      coronary sinus in that the infection was localized to the coronary sinus, the
      etiology was unclear, and the patient recovered uneventfully after surgery.

PMID- 15476572
TI  - Optimal antithrombotic management of anticoagulated patients with a history of
      myocardial infarction.
AB  - A common clinical dilemma exists for optimal antithrombotic management of a
      patient requiring oral anticoagulation (such as venous thromboembolism) and
      continued secondary myocardial infarction prophylaxis. Often aspirin will be
      continued concomitantly with the indicated oral anticoagulation therapy; however,
      additional benefits and increased risks of this practice have not been
      established. A systematic literature review was conducted to determine the
      benefits and risks of antithrombotic treatment strategies. Five clinical trials
      met the inclusion criteria and were evaluated to answer this clinical question.

PMID- 15476573
TI  - LRP5 and Wnt signaling: a union made for bone.

PMID- 15476574
TI  - Association between exercise and pubertal BMD is modulated by estrogen receptor
      alpha genotype.
AB  - Genetic and environmental factors contribute to bone mass, but the ways they
      interact remain poorly understood. This study of 245 pre- and early pubertal
      girls found that the PvuII polymorphism in the ER-alpha gene modulates the effect
      of exercise on BMD at loaded bone sites. INTRODUCTION: Impaired achievement of
      bone mass at puberty is an important risk factor for the development of
      osteoporosis in later life. Genetic, as well as environmental, factors contribute
      to bone mass, but the ways they interact with each other remain poorly
      understood. MATERIALS AND METHODS: We investigated the interaction between a
      PvuII polymorphism at the ER-alpha gene and physical activity (PA) on the
      modulation of bone mass and geometry in 245 10- to 13-year-old pre- and early
      pubertal Finnish girls. Level of PA was assessed using a questionnaire. Bone
      properties were measured using DXA and pQCT. The analyses were controlled for the
      effects of Tanner stage and body size index. RESULTS: Girls with heterozygote ER
      alpha genotype (Pp) and high PA had significantly higher bone mass and BMD, as
      well as thicker cortex, at loaded bone sites than their low-PA counterparts. No
      differences were found in bone properties of the distal radius, which is not a
      weight-bearing bone. Bone properties did not differ in either homozygote groups
      (PP and pp) regardless of the PA level. CONCLUSIONS: These findings suggest that
      the PvuII polymorphism in the ER-alpha gene may modulate the effect of exercise
      on BMD at loaded bone sites. The heterozygotes may benefit most from the effect
      of exercise, whereas neither of the homozygote groups received any significant
      improvement from high PA. Furthermore, high PA may hide the genetic influence on
      bone. Indeed, it seems that one may compensate one's less favorable Pp genotype
      by increasing leisure PA at early puberty.

PMID- 15476575
TI  - Neridronate prevents bone loss in patients receiving androgen deprivation therapy
      for prostate cancer.
AB  - Today, androgen deprivation therapy is a cornerstone of treatment for advanced
      prostate cancer, although it presents important complications such as
      osteoporosis. Neridronate, a relatively new bisphosphonate, is able to prevent
      bone loss in patients with prostate cancer during androgen ablation.
      INTRODUCTION: Androgen-deprivation therapy (ADT) is a cornerstone of treatment
      for advanced prostate cancer. This therapy has iatrogenic complications, such as
      osteoporosis. The aim of our study was to evaluate the efficacy of neridronate, a
      relatively new bisphosphonate, to prevent bone loss during androgen ablation.
      MATERIALS AND METHODS: Forty-eight osteoporotic patients with prostate cancer,
      treated with 3-month depot triptorelina, were enrolled and randomly assigned to
      two different treatment groups: group A (n = 24) was treated with a daily calcium
      and cholecalciferol supplement (500 mg of elemental calcium and 400 IU
      cholecalciferol), and group B (n = 24) received in addition to the same daily
      calcium and cholecalciferol supplement, 25 mg of neridronate given
      intramuscularly every month. All patients also received bicalutamide for 4 weeks.
      Lumbar and femoral BMD was evaluated by DXA at baseline and after 1 year of
      therapy; moreover, deoxypyridinoline (DPD) and bone alkaline phosphatase (BALP)
      were determined at the beginning, midway through, and at the end of the study.
      RESULTS: After 6 and 12 months, whereas patients treated only with calcium and
      cholecalciferol (group A) showed a marked bone loss, with increased levels of DPD
      and BALP compared with baseline values, patients treated also with neridronate
      (group B) had substantially unchanged levels of these markers. After 1 year of
      treatment, lumbar and total hip BMD decreased significantly in patients treated
      only with calcium and cholecalciferol (group A), whereas it did not change
      significantly at any skeletal site in patients treated also with neridronate
      (group B). No relevant side effects were recorded during our study. CONCLUSIONS:
      Neridronate is an effective treatment in preventing bone loss in the hip and
      lumbar spine in men receiving ADT for prostate cancer.

PMID- 15476576
TI  - Intravenous pamidronate prevents femoral bone loss and renal stone formation
      during 90-day bed rest.
AB  - Long-term bed rest has potential risks of bone loss and renal stone formation. We
      examined the effects of resistive exercise and intravenous pamidronate on BMD,
      bone turnover, urinary calcium, and renal stone formation in 25 healthy males
      during 90-day bed rest. Pamidronate prevented femoral bone loss and renal stone
      formation, but resistive exercise showed little effects. INTRODUCTION: Long-term
      bed rest increases the risks of bone loss and urinary stone formation. Resistive
      exercise increases bone formation, and bisphosphonates reduce bone resorption.
      However, the effects of muscle exercise and bisphosphonates have not been
      examined side-by-side. The objectives of this study are to compare the effects of
      pamidronate with resistive exercise on BMD and renal stone formation during
      prolonged bed rest. MATERIALS AND METHODS: Twenty-five male white volunteers, 26
      45 years of age, were randomly assigned to the control (n = 9), exercise (n = 9),
      and pamidronate (n = 7) groups and underwent 90-day 6 degrees head-down tilt bed
      rest. Exercise group performed squats and heel raises on a flywheel device for 30
      minutes every 3 days. Pamidronate (60 mg) was administered intravenously 14 days
      before bed rest. BMD of the head, forearm, lumbar spine, and proximal femur;
      biochemical bone markers; calcium (Ca) metabolism; and abdominal radiographs were
      examined during 90 days of bed rest and 360 days of reloading. RESULTS: In
      controls, proximal femoral BMD decreased, and bone resorption markers and urinary
      Ca increased during bed rest, along with development of renal stones in two of
      nine subjects. Resistive exercise increased bone formation but was unable to
      prevent femoral BMD decrease and increases in bone resorption and urinary Ca
      during bed rest, with formation of renal stones in four of nine subjects.
      Pamidronate maintained femoral BMD, reduced bone resorption and urinary Ca, and
      completely prevented renal stone formation. CONCLUSIONS: Resistive exercise
      increased bone formation but could not reduce bone resorption and the risk of
      renal stones. In contrast, inhibition of bone resorption by pamidronate could
      preserve bone mineral and reduce the risk of renal stone formation during
      prolonged bed rest.

PMID- 15476577
TI  - Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta
      patients receiving pamidronate.
AB  - This study evaluated factors influencing fracture (n = 197) and osteotomy (n =
      200) healing in children with moderate to severe OI. Pamidronate treatment was
      associated with delayed healing after osteotomy, but not after fracture. The data
      suggest that both pamidronate and mechanical factors influence bone healing in
      this cohort. INTRODUCTION: Intravenous pamidronate is widely used to treat
      children with moderate to severe osteogenesis imperfecta (OI). However, the
      effect of this treatment on bone healing is not well characterized. We therefore
      retrospectively analyzed the healing of lower limb fractures and osteotomies in
      children with moderate to severe OI, both before and after the start of
      pamidronate treatment. MATERIALS AND METHODS: Bone healing was evaluated on
      standard radiographs after 197 lower limb fractures (132 femur and 65 tibia) in
      82 patients (age at fracture, 0.0-19.9 years) and 200 intramedullary rodding
      procedures in 79 patients (age at surgery, 1.2-19.8 years). Delayed healing was
      diagnosed when a fracture or osteotomy line was at least partially visible 12
      months after the event. RESULTS: Delayed fracture healing was observed more
      frequently during than before pamidronate treatment. However, the effect of
      pamidronate was no longer significant when age differences were taken into
      account (odds ratio [OR], 1.76; 95% CI, 0.61-5.10). Better mobility status was a
      strong independent predictor of delayed healing after fractures that occurred
      during pamidronate treatment. After osteotomies, delayed healing was more
      frequent when pamidronate had been started before surgery (OR, 7.29; 95% CI, 2.62
      20.3), and this effect persisted after adjustment for multiple confounders.
      During pamidronate treatment, older age (OR per year of age, 1.25; 95% CI, 1.06
      1.47) and osteotomy of the tibia (OR, 3.51; 95% CI, 1.57-7.82) were independent
      predictors of delayed healing. CONCLUSIONS: This study suggests that pamidronate
      therapy is associated with delayed healing of osteotomy sites after
      intramedullary rodding procedures. Better mobility status, but not pamidronate
      treatment, seems to be predictive of delayed healing after fractures.

PMID- 15476578
TI  - Intermittent ibandronate preserves bone quality and bone strength in the lumbar
      spine after 16 months of treatment in the ovariectomized cynomolgus monkey.
AB  - The dose-dependent effect of ibandronate treatment on bone mass and architecture
      was assessed in a large animal study of OVX monkeys using microCT for
      quantitative bone morphometry and biomechanical testing for measures of bone
      strength. The study showed that intermittent ibandronate preserved lumbar spine
      bone quality and strength in these animals after 16 months of treatment.
      INTRODUCTION: Ibandronate is a bisphosphonate, which is a class of compounds
      that, in pharmacologically active doses, not only suppresses bone resorption and
      turnover but also prevents loss of bone mass and strength in the ovariectomized
      (OVX) rat. MATERIALS AND METHODS: We evaluated the effects of ibandronate on bone
      mass and architecture in the OVX cynomolgus macaque. Sixty-one adult female
      macaques were divided into five groups (N = 11-15): sham control, OVX control,
      and OVX low- (10 microg/kg), medium- (30 microg/kg), and high- (150 microg/kg)
      dose ibandronate. Treatment was administered by intravenous bolus injection every
      30 days for 16 months starting at ovariectomy. This dosing schedule is equivalent
      to a 3-monthly dosing regimen in human subjects over 4 years. Animals were killed
      at the conclusion of the study, and excised bone specimens of the first lumbar
      vertebra (L1) were evaluated for quantitative bone densitometry, morphometry, and
      mechanical properties. Architectural parameters were assessed by microCT
      including direct 3D bone morphometry. A measure of specimen strength was obtained
      using destructive compression testing. RESULTS AND CONCLUSIONS: A significant
      loss of bone mass and related changes in bone architecture after ovariectomy
      resulted in a reduction of whole bone strength as expressed by high correlations
      between architectural and mechanical properties. In this analysis, BMC was the
      best single predictor of whole bone strength (r2 = 67%). Nevertheless, including
      architectural indices in a multiple linear regression analysis increased that
      prediction to 88%. With respect to the treatment, the medium- and high-dose
      groups were not significantly different from the sham group for all bone mineral
      and structural parameters. Additionally, significant differences were seen for
      all measured parameters between the high-dose group and the OVX group, and for
      some parameters, between the medium-dose group and the OVX group. Intermittent
      ibandronate treatment effectively and dose-dependently prevented bone loss,
      architectural deterioration, and strength reduction in the lumbar spine of OVX
      monkeys.

PMID- 15476579
TI  - Dissociation between global markers of bone formation and direct measurement of
      spinal bone formation in osteoporosis.
AB  - Regional bone metabolism measured using 18F-fluoride PET was assessed in 72
      postmenopausal women classified as normal, osteopenic, or osteoporotic. Lower
      values of regional bone formation activity at the lumbar spine were seen in
      osteoporotic women, whereas global markers of bone formation were significantly
      increased. INTRODUCTION: Evaluations of global bone remodeling have revealed that
      increased bone turnover is a feature of patients with osteoporosis. The
      noninvasive functional imaging technique of 18F-fluoride positron emission
      tomography (PET) allows the direct quantitative assessment of bone metabolism at
      specific sites in the skeleton, including the clinically important site of the
      lumbar spine. MATERIALS AND METHODS: The aim of this study was to compare
      regional skeletal kinetics in 72 postmenopausal women (mean age, 61 years)
      classified as normal, osteopenic, or osteoporotic according to their BMD T score
      at the lumbar spine. Each woman had a dynamic PET scan of the lumbar spine after
      injection of 90 MBq 18F-fluoride ion and measurements of biochemical markers of
      bone formation and resorption. The arterial plasma input function was derived
      using aorta arterial activity from the PET image. Time-activity curves were
      obtained by placing regions of interest over the lumbar vertebrae. A three
      compartmental model was used to calculate bone blood flow (K1) and the net plasma
      clearance of tracer to bone mineral (Ki), reflecting regional osteoblastic
      activity (ml/minutes/ml). Rate constants k2, k3, and k4, which describe transport
      between plasma, the extracellular fluid (ECF) compartment, and the bone mineral
      compartment, were also measured. RESULTS: The net uptake of fluoride to the bone
      mineral compartment (Ki) was significantly lower in the osteoporotic group
      compared with both the osteopenic and normal groups, with a mean difference of
      0.005 ml/minutes/ml (16.7%). The fraction of the tracer in the extravascular
      tissue space that underwent specific binding to bone mineral (k3/k2 + k3) was
      also significantly reduced in the women classified as osteoporotic. In contrast,
      levels of bone-specific alkaline phosphatase (BSALP) were significantly higher in
      the osteoporotic group compared with the normal and osteopenic groups by 35% and
      27%, respectively. A significant negative correlation (r = -0.41) was observed
      between levels of BSALP and the fraction of the tracer that underwent specific
      binding to bone mineral. CONCLUSION: Lower values of Ki, a measurement of
      regional bone formation activity, were seen in women classified as osteoporotic,
      whereas levels of BSALP, a measure of global bone formation, were significantly
      increased. These findings are suggestive of increased global skeletal bone
      turnover in women with postmenopausal osteoporosis but with relatively reduced
      regional bone formation at the predominantly trabecular site of the lumbar spine.

PMID- 15476580
TI  - Interleukin-1beta and TNF-alpha act in synergy to inhibit longitudinal growth in
      fetal rat metatarsal bones.
AB  - We hypothesized that pro-inflammatory cytokines can act locally in the growth
      plate to impair longitudinal growth. In a model of cultured fetal rat metatarsal
      bones, we found that IL-1beta and TNF-alpha act in synergy to inhibit
      longitudinal growth, an effect linked to decreased proliferation and increased
      apoptosis of growth plate chondrocytes. IGF-I could partially reverse all these
      effects. INTRODUCTION: Children with chronic inflammatory conditions, such as
      Crohn's disease or rheumatoid arthritis, experience impaired longitudinal growth.
      The inflammatory process itself, which includes upregulation of the pro
      inflammatory cytokines interleukin (IL)-1beta, IL-6, and TNF-alpha, is believed
      to be at least partly responsible for the poor growth in these patients. This
      study aimed to clarify whether these cytokines can act locally in the growth
      plate to suppress longitudinal growth and whether any negative effects can be
      reversed by insulin-like growth factor-I (IGF-I). MATERIALS AND METHODS: The
      effects of cytokines on longitudinal bone growth were studied in fetal (day E20)
      rat metatarsal bones kept in culture. After a 7-day culture, the bones were
      sectioned, and chondrocyte proliferation was assessed by bromodeoxyuridine (BrdU)
      incorporation and apoptosis by TUNEL. RESULTS: When added separately, IL-1beta
      and TNF-alpha impaired longitudinal bone growth only at a high concentration (100
      ng/ml each; p < 0.05 versus control). In contrast, when added in combination, IL
      1beta and TNF-alpha potently inhibited growth at far lower concentrations (from 3
      ng/ml each; p < 0.001 versus control) and also decreased chondrocyte
      proliferation and increased apoptosis. Growth failure induced by the combination
      of IL-1beta and TNF-alpha (10 ng/ml each) could be counteracted by anti-IL-1beta
      (100 ng/ml; p < 0.001), anti-TNF-alpha (100 ng/ml; p < 0.001), or IGF-I (100
      ng/ml; p < 0.01). IL-6 did not affect longitudinal growth even when added in
      combination with IL-1beta or TNF-alpha (10 ng/ml each). CONCLUSIONS: We show that
      IL-1beta and TNF-alpha act in synergy to locally suppress longitudinal growth, an
      effect that can be partially reversed by IGF-I. Although growth hormone (GH)/IGF
      I may improve longitudinal growth in children with chronic inflammatory diseases,
      our results suggest that the inflammatory process itself must be targeted to
      achieve normal growth.

PMID- 15476581
TI  - Skeletal unloading alleviates the anabolic action of intermittent PTH(1-34) in
      mouse tibia in association with inhibition of PTH-induced increase in c-fos mRNA
      in bone marrow cells.
AB  - We analyzed the effect of unloading by tail suspension on the anabolic action of
      intermittent PTH in the tibia of growing mice. Unloading alleviated the PTH
      induced increase of bone formation and accelerated bone resorption, consequently
      reducing bone mass. Reduction of the PTH-induced anabolic actions on bone was
      associated with unloading, which was apparently related to suppression of c-fos
      mRNA expression in bone marrow. INTRODUCTION: The effects of intermittent
      parathyroid hormone (PTH) administration on unloading bone have not been well
      elucidated at the cellular and molecular levels. We tested the effects of PTH on
      unloaded tibias of tail-suspended mice. MATERIALS AND METHODS: Eighty male
      C57BL/6J mice, 8 weeks of age, were divided into four groups with loading or
      unloading and administration of PTH (40 microg/kg body weight) or vehicle five
      times per week. Mice were killed at 8 or 15 days, and both tibias were obtained.
      Bone histomorphometry of the trabecular bone in the proximal tibia, development
      of osteogenic cells, and mRNA expression of osteogenic molecules in bone marrow
      cells were assessed. RESULTS AND CONCLUSIONS: At 15 days of unloading, bone
      volume decreased in PTH-treated mice. The increase in the bone formation rate by
      PTH was depressed, and the osteoclast surface was thoroughly increased. The
      increase in alkaline phosphatase-positive colony-forming units-fibroblastic (CFU
      f) colonies induced by PTH was maintained and that of TRACP+ multinucleated cells
      enhanced. The PTH-induced increase in c-fos mRNA was depressed, but the increases
      in Osterix and RANKL mRNA were maintained. Unloading promoted the PTH-associated
      osteoclastogenesis and seemed to delay the progression of osteogenic
      differentiation in association with reduction of the PTH-dependent increase of c
      fos mRNA in bone marrow cells.

PMID- 15476582
TI  - Effects of calcitonin on subchondral trabecular bone changes and on
      osteoarthritic cartilage lesions after acute anterior cruciate ligament
      deficiency.
AB  - Because SBM may contribute to cartilage breakdown in OA, experimental OA was
      induced in dogs by transecting the anterior cruciate ligament of the knee and
      treating with either CT or a placebo. CT significantly reduced both SBM and
      cartilage lesions. This study supports the use of CT in the treatment of canine
      experimental OA. INTRODUCTION: Because subchondral bone remodeling (SBM) may
      contribute to cartilage breakdown in osteoarthritis (OA), we evaluated to what
      extend calcitonin (CT) might affect cartilage and bone changes in the early
      stages of canine experimental OA. MATERIALS AND METHODS: Twelve dogs underwent
      transection of the anterior cruciate ligament (ACLT) of the right knee. After
      ACLT, each animal received a daily nasal spray delivering either 400 U of CT (CT
      treated group; n = 6) or a placebo (PL-treated group; n = 6). At day 84 after
      surgery, animals were killed, and cartilage changes were graded. BMD and volume
      fraction (BVF) were assessed by pQCT in different regions of interest (ROIs) of
      the subchondral cancellous bone of tibial plateaus (TPs). Statistics included a 2
      x 2 factorial analysis with +/-CT as one factor and +/-ACLT as the other. RESULTS
      AND CONCLUSIONS: Nonoperated (N-OP) knees were normal in both groups. In the PL
      treated group, ACLT knees all exhibited OA changes, which predominated in the
      medial knee compartment. Furthermore, compared with N-OP knees, the BMD and BVF
      of ACLT joints were both markedly reduced in medial TP but not in lateral TP. In
      contrast, in the CT-treated group, cartilage OA lesions of ACLT knees were
      significantly reduced, and there was no difference in BMD and BFV between N-OP
      and ACLT knees. These findings suggest that the loss of subchondral trabeculae
      contributes to cartilage breakdown, possibly by enhancing cartilage deformation
      on joint loading. By counteracting bone loss, CT reduced cartilage OA lesions,
      and thus, might be useful in the treatment of OA in cruciate-deficient dogs.

PMID- 15476583
TI  - Long-term sensitivity of uterus and hypothalamus/pituitary axis to 17beta
      estradiol is higher than that of bone in rats.
AB  - We examined the long-term sensitivity of uterus and bone to low-dose 17beta
      estradiol in a 4-month experiment in OVX rats and found that a dose of estradiol
      that fully protected against uterine atrophy did not protect against bone loss.
      Our results suggest higher estrogen sensitivity of the uterus compared with bone.
      INTRODUCTION: Estrogen is essential for the function of reproductive tissues and
      for the normal acquisition and maintenance of bone mass in females. This study
      was designed to examine the long-term sensitivity of the uterus and bone to low
      dose estrogen. MATERIALS AND METHODS: In preliminary experiments, we determined
      the lowest subcutaneous dose of 17beta-estradiol able to fully protect against
      uterine atrophy in ovariectomized (OVX) rats. This dose was found to be 1.5
      microg/kg, given five times per week. Subsequently, groups of sham-operated
      (SHAM) or OVX 6-month-old rats (n = 8 each) were subcutaneously injected with
      vehicle or 1.5 microg/kg 17beta-estradiol five times per week. All animals were
      killed 4 months after surgery. Serum osteocalcin and urinary deoxypyridinoline
      were measured as biochemical markers of bone turnover. Bones were analyzed by
      bone histomorphometry and pQCT. RESULTS AND CONCLUSIONS: Our study clearly showed
      that a dose of estradiol that restores physiological estradiol serum levels,
      fully maintains uterine weight in OVX rats at the SHAM control level, and
      suppresses serum follicle-stimulating hormone (FSH) by 67% relative to OVX
      vehicle controls does not provide significant protection against OVX-induced bone
      loss at different cancellous and cortical bone sites. We conclude that the long
      term sensitivity of the uterus and the hypothalamus/pituitary axis to 17beta
      estradiol is higher than that of bone in rats.

PMID- 15476584
TI  - Additive protective effects of estrogen and androgen treatment on trabecular bone
      in ovariectomized rats.
AB  - Both ER and AR activation regulates trabecular bone mass. We show that combined
      estrogen and androgen treatment results in additive protection of trabecular bone
      in OVX rats. This may in part be attributable to the effect of AR activation to
      attenuate the inhibitory effect of ER activation on bone formation. INTRODUCTION:
      Sex steroids are important regulators of trabecular bone mass. Both estrogen
      receptor (ER) and androgen receptor (AR) activation results in increased
      trabecular bone mass. The aim of this study was to investigate if combined
      estrogen and androgen treatment might be beneficial in the treatment of
      trabecular bone loss. MATERIALS AND METHODS: Twelve-week-old female rats were
      ovariectomized (OVX) and treated with vehicle (V), 17beta-estradiol (E2; ER
      activation), dihydrotestosterone (DHT; AR activation), or the combination (E2 +
      DHT) for 6 weeks. The skeletal phenotype was analyzed by pQCT, microCT,
      histomorphometry of growth plates, and serum levels of biochemical bone markers.
      RESULTS: Both E2 (+121% over V) and DHT (+34%) preserved the trabecular
      volumetric BMD (tvBMD) in OVX rats. The effect of E2 and DHT on tvBMD was
      additive, resulting in a 182% increase over V in the rats given E2 + DHT. MicroCT
      analyses of the trabecular bone microstructure revealed that the effect of E2 and
      DHT was additive on the number of trabeculae. E2 treatment reduced serum markers
      of both bone resorption (collagen C-terminal telopeptide) and bone formation
      (osteocalcin), indicating reduced bone turnover. Addition of DHT to E2 treatment
      did not modulate the effects of E2 on the marker of bone resorption, whereas it
      attenuated the inhibitory effect of E2 on the bone formation marker, which might
      explain the additive protective effect of E2 and DHT on trabecular bone mass. In
      contrast, DHT partially counteracted the suppressive effect of E2 on longitudinal
      bone growth and the E2-induced alterations in growth plate morphology.
      CONCLUSIONS: These findings show that combined estrogen and androgen treatment
      results in additive protective effects on trabecular bone in OVX rats. Our data
      suggest that a combined treatment with selective ER and AR modulators might be
      beneficial in the treatment of osteoporosis.

PMID- 15476585
TI  - Cell-cell interaction mediated by cadherin-11 directly regulates the
      differentiation of mesenchymal cells into the cells of the osteo-lineage and the
      chondro-lineage.
AB  - We studied cadherin-11 function in the differentiation of mesenchymal cells.
      Teratomas harboring the cadherin-11 gene generated bone and cartilage
      preferentially. Cadherin-11 transfectants of C2C12 cells and cadherin-11 and/or N
      cadherin transfectants of L cells showed that cadherin-11 together with N
      cadherin-induced expression of ALP and FGF receptor 2. These results suggest that
      cadherin-11 directly regulates the differentiation of mesenchymal cells into the
      cells of the osteo-lineage and the chondro-lineage in a different manner from N
      cadherin. INTRODUCTION: Cell-cell interaction is an essential event for tissue
      formation; however, the role of cell-cell adhesion in mesenchymal tissue
      formation as well as in cell differentiation in this tissue remains unclear.
      cadherins, which are calcium-dependent cell adhesion receptors, form adherence
      junctions after adherence and aggregation of cells. Because cadherin-11 as well
      as N-cadherin has been reported to be a mesenchyme-related cadherin, we examined
      the cadherin-11 action in teratomas and in the cell lines C2C12 and L cell.
      Herein, we show that cell-cell interaction mediated by cadherin-11 is responsible
      for bone and cartilage formation. MATERIALS AND METHODS: It has been previously
      reported that N-cadherin-expressing E-cadherin-/- ES transfectants formed
      neuroepithelium and cartilage in teratomas. Thus, we transfected the E-cadherin-/
      ES cell line with the cadherin-11 gene. Moreover, we also transfected C2C12
      cells and L cells with the cadherin-11 gene for morphological analysis and study
      of the induced differentiation at the molecular level. RESULTS AND CONCLUSION:
      Teratomas derived from embryonic stem cells in which the cadherin-11 gene had
      been expressed exogenously contained bone and cartilage preferentially, showing
      that cadherin-11 is involved in mesenchymal tissue formation, specifically in
      controlling the differentiation of these cells into osteoblasts and chondrocytes.
      Therefore, we further examined the functional difference between cadherin-11 and
      N-cadherin. The expression patterns of cadherin-11 and N-cadherin in cells of the
      mouse osteoblastic cell line MC3T3-E1 showed that each cadherin was located
      independently of the cell-cell adhesion site and acted individually. In hanging
      drop cultures, cadherin-11 L cell transfectants aggregated in a sheet-like
      structure, whereas N-cadherin transfectants aggregated in a spherical form,
      indicating that each cadherin confers a different 3D architecture because of its
      individual adhesive property. To investigate the molecular mechanism of cadherin
      11 action in cell differentiation, we analyzed cadherin-11 transfectants of C2C12
      cells and cadherin-11 and/or N-cadherin transfectants of L cells and showed that
      cadherin-11, together with N-cadherin, induced expression of alkaline phosphatase
      (ALP) and fibroblast growth factor receptor 2. These results suggest that
      cadherin-11 directly regulates the differentiation of mesenchymal cells into the
      cells of the osteo-lineage and the chondro-lineage in a different manner from N
      cadherin.

PMID- 15476586
TI  - Downregulation of osteoblast markers and induction of the glial fibrillary acidic
      protein by oncostatin M in osteosarcoma cells require PKCdelta and STAT3.
AB  - The effects of OSM on proliferation and differentiation of osteosarcoma and
      nontransformed osteoblasts were analyzed. OSM downregulates osteoblast markers
      but induces the glial fibrillary acidic protein by the combined activation of
      PKCdelta and STAT3, offering new lines of therapeutic investigations.
      INTRODUCTION: Oncostatin M (OSM) is a multifunctional cytokine of the interleukin
      6 family implicated in embryonic development, differentiation, inflammation, and
      regeneration of various tissues, mainly the liver, bone, and the central nervous
      and hematopoietic systems. One particularity of OSM relies on its growth
      inhibitory and pro-differentiating effects on a variety of tumor cell lines such
      as melanoma, providing arguments for a therapeutic application of OSM. The
      objective of this study was to analyze the effects of OSM on osteosarcoma cell
      lines proliferation and differentiation. MATERIALS AND METHODS: Proliferation was
      analyzed by 3H thymidine incorporation. Differentiation was analyzed by
      semiquantitative RT-PCR and immunocytochemistry for various markers. Alizarin red
      S staining was used to evaluate bone nodule formation. Morphological changes were
      studied by confocal and electron microscopy. Western blotting, kinases
      inhibitors, and dominant negative STAT3 were used to identified the signaling
      pathways implicated. RESULTS: OSM inhibits the growth of rat osteosarcoma cell
      lines as well as normal osteoblasts, in correlation with induction of the cyclin
      dependent kinases inhibitor p21WAF1. However, OSM reduces osteoblast markers such
      as alkaline phosphatase, osteocalcin, and bone sialoprotein, leading to strong
      inhibition of mineralized nodule formation. This inhibitory effect is restricted
      to mature osteoblasts and differentiated osteosarcoma because OSM effectively
      stimulates osteoblast markers and bone nodule formation in early, but not late,
      bone marrow mesenchymal stem cell (BMSC) cultures. In osteosarcoma cells or BMSC,
      OSM induces expression of the glial fibrillary acidic protein (GFAP) as well as
      morphological and ultrastructural changes, for example, elongated shape and
      bundles of microfilaments in cell processes. Rottlerin (PKCdelta inhibitor), and
      to a lesser degree UO126 (MEK/ERK inhibitor), prevents the loss of osteoblastic
      markers by OSM, whereas dominant negative STAT3 prevents GFAP induction.
      CONCLUSIONS: These results highlight the particular gene expression profile of
      OSM-treated osteosarcoma cells and BMSCs, suggesting either a osteocytic or a
      glial-like phenotype. Together with the implication of PKCdelta, ERK1/2, and
      STAT3, these results offer new lines of investigations for neural cell
      transplantation and osteosarcoma therapy.

PMID- 15476587
TI  - Residues determining the binding specificity of uncompetitive inhibitors to
      tissue-nonspecific alkaline phosphatase.
AB  - Recent data have pointed to TNALP as a therapeutic target for soft-tissue
      ossification abnormalities. Here, we used mutagenesis, kinetic analysis, and
      computer modeling to identify the residues important for the binding of known ALP
      inhibitors to the TNALP active site. These data will enable drug design efforts
      aimed at developing improved specific TNALP inhibitors for therapeutic use.
      INTRODUCTION: We have shown previously that the genetic ablation of tissue
      nonspecific alkaline phosphatase (TNALP) function leads to amelioration of soft
      tissue ossification in mouse models of osteoarthritis and ankylosis (i.e., Enpp1
      /- and ank/ank mutant mice). We surmise that the pharmacologic inhibition of
      TNALP activity represents a viable therapeutic approach for these diseases. As a
      first step toward developing suitable TNALP therapeutics, we have now clarified
      the residues involved in binding well-known uncompetitive inhibitors to the TNALP
      active site. MATERIALS AND METHODS: We compared the modeled 3D structure of TNALP
      with the 3D structure of human placental alkaline phosphatase (PLALP) and
      identified the residues that differ between these isozymes within a 12 A radius
      of the active site, because these isozymes differ significantly in inhibitor
      specificity. We then used site-directed mutagenesis to substitute TNALP residues
      to their respective homolog in PLALP. In addition, we mutagenized most of these
      residues in TNALP to Ala and the corresponding residues in PLALP to their TNALP
      homolog. All mutants were characterized for their sensitivity toward the
      uncompetitive inhibitors l-homoarginine (L-hArg), levamisole, theophylline, and l
      phenylalanine. RESULTS AND CONCLUSIONS: We found that the identity of residue 108
      in TNALP largely determines the specificity of inhibition by L-hArg. The
      conserved Tyr-371 is also necessary for binding of L-hArg. In contrast, the
      binding of levamisole to TNALP is mostly dependent on His-434 and Tyr-371, but
      not on residues 108 or 109. The main determinant of sensitivity to theophylline
      is His-434. Thus, we have clarified the location of the binding sites for all
      three TNALP inhibitors, and we have also been able to exchange inhibitor
      specificities between TNALP and PLALP. These data will enable drug design efforts
      aimed at developing improved, selective, and drug-like TNALP inhibitors for
      therapeutic use.

PMID- 15476588
TI  - Secreted frizzled-related protein-1 inhibits RANKL-dependent osteoclast
      formation.
AB  - We determined that sFRP-1 mRNA was differentially expressed by osteoblast/stromal
      cell lines and that sFRP-1 neutralizing antibodies and siRNA complementary to
      sFRP-1 coding sequence enhanced, while recombinant sFRP-1 inhibited, osteoclast
      formation. In studying the mechanism of action for sFRP-1, we found that sFRP-1
      could bind recombinant RANKL. These results suggest potential cross-talk between
      Wnt and RANKL pathways. INTRODUCTION: Osteoclast formation in normal bone
      remodeling requires the presence of osteoblast lineage cells that express RANKL
      and macrophage-colony-stimulating factor (M-CSF), which interact with their
      cognate receptors on the osteoclast precursor. We identified secreted Frizzled
      related protein-1 (sFRP-1), which is known to bind to Wnt and inhibit the Wnt
      signaling pathway, as an osteoblast-derived factor that impinges on osteoclast
      formation and activity. MATERIALS AND METHODS: Differential display of mRNA from
      osteoblast lineage cell lines established sFRP-1 to be highly expressed in an
      osteoclast supporting cell line. sFRP-1 expression in bone was determined by in
      situ hybridization, and the effects of sFRP-1 on osteoclast formation were
      determined using a neutralizing antibody, siRNA, for sFRP-1 and recombinant
      protein. RESULTS: In situ hybridization revealed sFRP-1 mRNA expression in
      osteoblasts and chondrocytes in murine bone. sFRP-1 mRNA expression could be
      elevated in calvarial primary osteoblasts in response to prostaglandin E2 (PGE2)
      or interleukin (IL)-11, whereas many other osteotropic agents (e.g., IL-1, IL-6,
      calcitrol, parathyroid hormone) were without any effect. In vitro assays of
      osteoclast formation established sFRP-1 to be an inhibitor of osteoclast
      formation. Neutralizing antibodies against sFRP-1 enhanced TRACP+ mononuclear and
      multinuclear osteoclast formation (3- and 2-fold, respectively) in co-cultures of
      murine osteoblasts with spleen cells, whereas siRNA complementary to sFRP-1
      coding sequence significantly enhanced osteoclast formation in co-cultures of
      KUSA O (osteoblast/stromal cell line) and bone marrow cells, cultured in the
      presence of PGE2 and 1,25(OH)2 vitamin D3. Recombinant sFRP-1 dose-dependently
      inhibited osteoclast formation in osteoblast/spleen co-cultures, RANKL + M-CSF
      treated splenic cultures, and RANKL-treated RAW264.7 cell cultures, indicating a
      direct action of sFRP-1 on hematopoietic cells. Consistent with this, sFRP-1 was
      found to bind to RANKL in ELISAs. CONCLUSION: sFRP-1 is expressed by osteoblasts
      and inhibits osteoclast formation. While sFRP-1 activity might involve the
      blocking of endogenous Wnt signaling, our results suggest that, alternatively, it
      could be because of direct binding to RANKL. This study describes a new mechanism
      whereby osteoblasts regulate osteoclastogenesis through the expression and
      release of sFRP-1.

PMID- 15476589
TI  - Rho and Rho kinase are involved in parathyroid hormone-stimulated protein kinase
      C alpha translocation and IL-6 promoter activity in osteoblastic cells.
AB  - The role of small G-proteins in PTH-stimulated PKC translocation and IL-6
      promoter expression in UMR-106 cells was determined. The effects of PTH(1-34) and
      PTH(3-34) in stimulating PKCalpha translocation and IL-6 were inhibited by agents
      that interfere with the activity of small G-proteins of the Rho family and with
      the downstream kinase Rho kinase. INTRODUCTION: Activation of protein kinase C
      (PKC) is a signaling mechanism by which parathyroid hormone (PTH) modulates
      interleukin-6 (IL-6) in osteoblasts, leading to osteoclastogenesis and bone
      resorption. PKCalpha and PKCbetaI are translocated after treatment with PTH in
      UMR-106 osteoblastic cells; however, the pathway leading to PKC isozyme
      translocation is not established. Diacylglycerol (DAG) generation from
      phospholipase D (PLD) is one pathway of PKC activation, and PTH-mediated PLD
      activity is dependent on small G-proteins of the Rho family. This study
      investigated whether Rho proteins modulate the PKCalpha translocation and IL-6
      promoter activity stimulated by PTH in UMR-106 cells. MATERIALS AND METHODS: UMR
      106 cells were treated with PTH(1-34) or PTH(3-34). PKC translocation was
      determined by immunofluorescence, Rho A activation by Rhotekin assay and by
      translocation assessed by Western blotting in membrane and cytosol fractions, and
      IL-6 promoter expression by luciferase assay. RESULTS AND CONCLUSIONS: Inhibition
      of Rho proteins with Clostridium difficile toxin B or inhibition of Rho
      prenylation with GGTI attenuated PTH(1-34)- and PTH(3-34)-stimulated
      translocation of endogenous PKCalpha and IL-6 promoter activity. Expression of a
      constitutively active RhoA (RhoA63L) mimicked the effect of PTH(1-34) or PTH(3
      34) to promote membrane localization of PKCalpha, whereas cells expressing a
      dominant negative RhoA (RhoA19N) did not respond to PTH(1-34) or PTH(3-34). The
      Rho kinase inhibitor Y27632 attenuated PTH(1-34)- and PTH(3-34)-stimulated
      PKCalpha translocation and IL-6 promoter activation. Rho seemed to be acting at a
      step before production of diacylglycerol (DAG), because the stimulation of
      PKCalpha translocation by the DAG mimetic phorbol 12,13 dibutyrate (PDBu) was
      unaffected by C. difficile toxin B or Y27632. These results indicate that Rho
      proteins are an important component of PTH signaling in osteoblastic cells and
      provide further demonstration of convergence between PKC and small G-protein
      signaling pathways.

PMID- 15476590
TI  - Growth hormone attenuates the transcriptional activity of Runx2 by facilitating
      its physical association with Stat3beta.
AB  - We document that GH controls osteoblast function by modulating the biological
      activity of the osteospecific transcription factor Runx2. Evidence is provided
      for a physical interaction between Runx2 and Stat3beta, which is enhanced by GH
      and downregulates the transcriptional properties of this key osteogenic
      regulator. INTRODUCTION: Growth hormone (GH) signals to bone either through
      insulin-like growth factor-1 or directly by influencing the function of
      osteoblasts, the bone-forming cells. This study aimed at exploring the molecular
      events that underlie the direct biological action of GH on osteoblastic cells,
      and specifically, the effects that it might exert on the function of the bone
      specific transcriptional regulator Runx2. MATERIALS AND METHODS: The GH
      responsive human osteoblastic cell line Saos-2 was used as our experimental
      system. Western blot analyses were used to monitor the presence of several
      parameters known to be affected by GH in these cells (i.e., downregulation of GH
      receptor, induction of STATs, and extracellular signal-regulated kinase [ERK]
      mitogen-activated protein kinase [MAPK] pathways). Electrophoretic mobility shift
      assays were used to assess Runx2 and Stat3 binding activity on an osteoblast
      specific element (OSE2) after GH treatment. A combination of yeast two-hybrid and
      co-immunoprecipitation assays were performed to test for the existence of a
      physical Runx2.Stat3beta association. Finally, co-transfection experiments were
      used to investigate the interplay of the two transcription factors on the
      activity of a p6OSE2-Luc promoter after GH stimulation. RESULTS: We show that GH
      signaling through Stat3/ERK MAPK potentiates the DNA binding activity of Runx2
      but, at the same time, restrains its transcriptional potential. Moreover, a novel
      physical interaction of Runx2 with transcription factor Stat3beta, which is
      enhanced by GH stimulation, was documented both in vitro and in vivo.
      Importantly, this interaction impairs the transcriptional activity of Runx2
      without affecting its DNA binding capacity. CONCLUSION: Our data provide the
      first evidence that GH modulates the transcriptional function of Runx2 in
      osteoblastic cells by promoting its inhibitory interaction with Stat3beta.
      Shedding light on such mechanisms will contribute to a better understanding of GH
      effects on skeletal homeostasis that may impact on decisions at the clinical
      level, especially in diseases affecting bone quantity and quality (e.g.,
      osteoporosis).

PMID- 15476592
TI  - Impact of genetic polymorphisms in DNA repair enzymes on drug resistance in lung
      cancer.

PMID- 15476591
TI  - Sesquiterpene lactone parthenolide blocks lipopolysaccharide-induced osteolysis
      through the suppression of NF-kappaB activity.
AB  - Effective treatment for bacteria-induced bone lytic diseases is not yet
      available. In this study, we showed that PAR, an NF-kappaB inhibitor found in
      medicinal herbs, can block LPS-induced osteolysis. PAR does this by inhibiting
      osteoclastogenesis and bone resorption and promoting apoptosis of osteoclasts
      through the suppression of NF-kappaB activity. INTRODUCTION: Osteolysis induced
      by chronic gram-negative bacterial infection underlies many bone diseases such as
      osteomyelitis, septic arthritis, and periodontitis. Drugs that inhibit
      lipopolysaccharide (LPS)-induced osteolysis are critically needed for the
      prevention of bone destruction in infective bone diseases. In this study, we
      investigated the effect of parthenolide (PAR) on LPS-induced osteolysis in vivo
      and studied its role in osteoclastogenesis, bone resorption, apoptosis, and NF
      kappaB activity. MATERIALS AND METHODS: The LPS-induced osteolysis in the mouse
      calvarium model was used to examine the effect of PAR in vivo. RANKL-induced
      osteoclast differentiation from RAW264.7 cells and bone resorption assays were
      used to assess the effect of PAR in vitro. Assays for NF-kappaB activation, p65
      translocation, and IkappaB-alpha degradation were used to determine the mechanism
      of action of PAR in osteoclasts and their precursors. Flow cytometry and confocal
      microscopic analysis were used to examine cell apoptosis. Semiquantitative RT-PCR
      was performed to examine the effect of PAR on gene expression of RANK and TRAF6.
      RESULTS: We found that PAR (0.5 and 1 mg/kg), injected simultaneously with LPS
      (25 mg/kg) or 3 days later, blocked the LPS-induced osteolysis in the mouse
      calvarium model. In vitro studies showed that low concentrations of PAR (<1
      microM) inhibited in vitro osteoclastogenesis and osteoclastic bone resorption,
      whereas higher concentrations (>5 microM) triggered apoptotic cell death of
      osteoclasts and their precursor cells in a dose-dependent manner. Furthermore,
      PAR inhibited LPS-induced NF-kappaB activation, p65 translocation, and IkappaB
      alpha degradation both in mature osteoclasts and their precursors in a time- and
      dose-dependent manner. In addition, PAR inhibited NF-kappaB activation induced by
      osteoclastogenic factors RANKL, interleukin (IL)-1beta, or TNF-alpha to varying
      degrees and reduced the gene expression of RANK and TRAF6. CONCLUSION: The NF
      kappaB pathway is known to mediate both osteoclast differentiation and survival.
      These findings indicate that PAR blocks LPS-induced osteolysis through the
      suppression of NF-kappaB activity and suggest that it might have therapeutic
      value in bacteria-induced bone destruction.

PMID- 15476593
TI  - Early clinical data with small-molecule vascular endothelial growth factor
      tyrosine kinase receptor inhibitors.

PMID- 15476594
TI  - Early-stage non-small-cell lung cancer: current perspectives in combined-modality
      therapy.
AB  - The most effective treatment for patients with early-stage non-small-cell lung
      cancer (NSCLC) remains complete surgical resection, providing the disease is
      medically operable and adequately staged. The effectiveness of surgical
      resection, however, is limited by high rates of distant recurrence caused by the
      presence of metastatic disease that is not apparent at the time of surgery. Thus,
      induction, adjuvant chemotherapy, and radiation therapy, as well as a combination
      of both, have been studied for their ability to reduce local and distant
      recurrence rates and to improve survival. Adjuvant chest radiation therapy
      following resection decreases local relapse rates but also decreases overall
      patient survival, with an increase in the hazard ratio of death. A previous
      metaanalysis of cisplatin-based adjuvant chemotherapy showed a 13% reduction in
      the hazard ratio of death and a 5% improvement in 5-year survival, but the
      differences in the small sample failed to reach statistical significance. Newer 2
      drug combinations were shown to reduce the hazard ratio of death by 14%, with a
      4.3% improvement in 5-year survival in the largest trial recently reported. These
      newer 2-drug combinations also have the benefits of reduced toxicity and improved
      delivery. Induction chemotherapy offers several potential advantages compared
      with adjuvant chemotherapy, such as improved delivery, early control of
      micrometastatic disease, and reduction of the primary tumor size prior to
      surgery, thus allowing for more conservative and possibly complete resection of
      the tumor. A number of clinical trials have shown that induction chemotherapy is
      safe and feasible, with no significant increase in surgical complications, and
      results in favorable survival rates in patients with resectable NSCLC. A number
      of phase III randomized trials are currently under way to confirm the benefits of
      induction chemotherapy in patients with stage IB-IIIA NSCLC and to compare
      induction chemotherapy versus adjuvant chemotherapy following surgery versus
      surgery alone. In addition, biologically targeted agents are currently under
      study for patients with advanced NSCLC.

PMID- 15476595
TI  - Gemcitabine in patients with non-small-cell lung cancer previously treated with
      platinum-based chemotherapy: a phase II California cancer consortium trial.
AB  - A phase II trial was designed to evaluate the efficacy and toxicity of
      gemcitabine in patients with non-small-cell lung cancer (NSCLC) previously
      treated with platinum-containing regimens and prospectively categorized for
      platinum response status. Treatment consisted of gemcitabine 1000 mg/m2 given
      intravenously on days 1 and 8 of a 21-day cycle. The status of p53 in
      pretreatment tumor tissue was assessed by immunohistochemistry (IHC). Sixty-one
      patients who progressed or recurred following platinum-based therapy were
      enrolled, 26 platinum-sensitive and 35 platinum-refractory. A median of 4
      treatment courses (range, 2-7 courses) was delivered. Of the 55 patients
      assessable for response, there was 1 confirmed complete response and 3 with a
      confirmed partial response for an overall response proportion of 7%. Twenty-one
      patients had stable disease while 28 progressed and 2 patients had an unconfirmed
      partial response. Three of the responders (2 confirmed, 1 unconfirmed) were
      platinum-refractory. Median progression-free survival (PFS) and overall survival
      for all patients were 4.1 months and 8.6 months, respectively. Median PFS and
      overall survival for the platinum-sensitive and platinum-refractory cohorts were
      5.4 months versus 3.1 months, and 11.9 months versus 7.1 months, respectively.
      Toxicity was principally hematologic with grade 3/4 neutropenia in 21% and grade
      4 platelets in 8%. There were no treatment-related deaths. Twenty-four of 33
      patients (73%) had p53-positive tumors. Although no significant association
      between platinum sensitivity and p53 status was seen, patients with platinum
      sensitive disease and negative p53 by IHC had a trend toward longer survival
      compared to those with platinum-refractory disease and/or p53 positivity (P =
      0.06). We concluded that salvage gemcitabine in this dose and schedule is safe
      and tolerable in previously platinum-treated patients with NSCLC.

PMID- 15476596
TI  - Bronchioalveolar cell carcinoma: radiologic appearance and dilemmas in the
      assessment of response.
AB  - Bronchioalveolar cell carcinomas (BACs), a subset of primary lung
      adenocarcinomas, are uncommon. Histologically, they are a diverse group of
      malignancies. The diagnosis is restricted to adenocarcinomas that grow in a
      lepidic manner and that have no stromal, vascular, or pleural invasion. Their
      histologic diversity leads to varied radiologic manifestations that are often
      indistinguishable from those of other primary non-small-cell lung cancers
      (NSCLC). However, typical manifestations, many of which can be attributed to
      lepidic growth, have been reported. Radiologic manifestations include a solitary
      peripheral pulmonary nodule, airspace disease, and multiple nodules and a
      combination of these findings can be present in a single patient. The most common
      manifestation, a solitary pulmonary nodule, is usually indistinguishable from
      other primary NSCLC. However, pseudocavitation and air bronchograms within the
      nodule can be useful in suggesting the correct diagnosis. In addition to aiding
      in the diagnosis of BAC, radiologic imaging is an important component in the
      evaluation of the therapeutic efficacy of treatment; serial measurements of tumor
      size before and after treatment are commonly used to assess response. However,
      BACs that are consolidative or ground-glass in nature present challenges in tumor
      response determination. Other imaging modalities, such as positron emission
      tomography scanning, may prove helpful in assessing the metabolic response to
      therapy but have yet to be proven effective.

PMID- 15476597
TI  - Antiapoptotic signaling pathways in non-small-cell lung cancer: biology and
      therapeutic strategies.
AB  - One of the hallmarks of lung cancer is the deregulation of apoptotic or
      programmed cell death mechanisms usually found in normal cells that allow for
      corrupted cells to undergo cellular suicide. This includes mechanisms that
      attenuate proapoptotic pathways and/or amplify antiapoptotic pathways. Increasing
      evidence suggests that lung cancer cells use multiple and perhaps redundant
      pathways to maintain survival. Increasing knowledge of these pathways offers a
      better understanding of the biology of lung cancer as well as novel therapeutic
      strategies that can enhance lung cancer cell death. This review discusses the
      apoptotic machinery and signal transduction pathways that regulate apoptosis,
      methods of identifying the presence of activated survival signaling pathways in
      human lung cancers, and the clinical significance and relevance for therapy for
      patients with lung cancer.

PMID- 15476598
TI  - Gefitinib in patients with brain metastases from non-small-cell lung cancer:
      review of 15 clinical cases.
AB  - The clinical efficacy of gefitinib, a tyrosine kinase inhibitor of epidermal
      growth factor receptor (EGFR), on brain metastases (BMs) from non-small-cell lung
      cancer (NSCLC) was evaluated. Fifteen patients with recurrent NSCLC with
      metastasis to the brain were treated with gefitinib. The objective tumor response
      rate (60%; 9 of 15 patients) for BM was the same as for primary tumors. The
      median time to response of BM was 26 days. In 8 of 9 patients who exhibited
      partial response in the thoracic lesion, BM showed dramatic regression, including
      1 complete response. One patient with stable primary tumor also exhibited partial
      response in BM with this monotherapy. Brain metastasis-related neurologic
      symptoms such as hemiparesis, dysarthria, dysphagia, and vertigo improved or
      disappeared with the objective response of BM as confirmed by magnetic resonance
      imaging. Central nervous system toxicities were not observed during the
      treatment. Four of the 9 BM responders are still under treatment with neither
      adverse events nor disease progression. Two discontinued the treatment because of
      severe hepatic toxicity and 3 died because of acquired resistance in pulmonary
      lesions, even though partial response was observed in the BMs. Finally, median
      duration of response of BM was 8.7 months and median overall survival was 8.3
      months (range, 1.8 to > 15.7 months). Molecular targeted therapy against EGFR
      could be an option for the treatment of BM from NSCLC refractory to conventional
      chemotherapy plus radiation therapy because it has demonstrated a distinct
      therapeutic potential against BM compared with primary lung tumor and
      extracranial metastases.

PMID- 15476599
TI  - Predicting axonal response to molecular gradients with a computational model of
      filopodial dynamics.
AB  - Axons are often guided to their targets in the developing nervous system by
      attractive or repulsive molecular concentration gradients. We propose a
      computational model for gradient sensing and directed movement of the growth cone
      mediated by filopodia. We show that relatively simple mechanisms are sufficient
      to generate realistic trajectories for both the short-term response of axons to
      steep gradients and the long-term response of axons to shallow gradients. The
      model makes testable predictions for axonal response to attractive and repulsive
      gradients of different concentrations and steepness, the size of the
      intracellular amplification of the gradient signal, and the differences in
      intracellular signaling required for repulsive versus attractive turning.

PMID- 15476600
TI  - Insect-inspired estimation of egomotion.
AB  - Tangential neurons in the fly brain are sensitive to the typical optic flow
      patterns generated during egomotion. In this study, we examine whether a
      simplified linear model based on the organization principles in tangential
      neurons can be used to estimate egomotion from the optic flow. We present a
      theory for the construction of an estimator consisting of a linear combination of
      optic flow vectors that incorporates prior knowledge about the distance
      distribution of the environment and about the noise and egomotion statistics of
      the sensor. The estimator is tested on a gantry carrying an omnidirectional
      vision sensor. The experiments show that the proposed approach leads to accurate
      and robust estimates of rotation rates, whereas translation estimates are of
      reasonable quality, albeit less reliable.

PMID- 15476601
TI  - Correlated firing improves stimulus discrimination in a retinal model.
AB  - Synchronous firing limits the amount of information that can be extracted by
      averaging the firing rates of similarly tuned neurons. Here, we show that the
      loss of such rate-coded information due to synchronous oscillations between
      retinal ganglion cells can be overcome by exploiting the information encoded by
      the correlations themselves. Two very different models, one based on axon
      mediated inhibitory feedback and the other on oscillatory common input, were used
      to generate artificial spike trains whose synchronous oscillations were similar
      to those measured experimentally. Pooled spike trains were summed into a
      threshold detector whose output was classified using Bayesian discrimination. For
      a threshold detector with short summation times, realistic oscillatory input
      yielded superior discrimination of stimulus intensity compared to rate-matched
      Poisson controls. Even for summation times too long to resolve synchronous
      inputs, gamma band oscillations still contributed to improved discrimination by
      reducing the total spike count variability, or Fano factor. In separate
      experiments in which neurons were synchronized in a stimulus-dependent manner
      without attendant oscillations, the Fano factor increased markedly with stimulus
      intensity, implying that stimulus-dependent oscillations can offset the increased
      variability due to synchrony alone.

PMID- 15476602
TI  - A temporal stability approach to position and attention-shift-invariant
      recognition.
AB  - Incorporation of visual-related self-action signals can help neural networks
      learn invariance. We describe a method that can produce a network with invariance
      to changes in visual input caused by eye movements and covert attention shifts.
      Training of the network is controlled by signals associated with eye movements
      and covert attention shifting. A temporal perceptual stability constraint is used
      to drive the output of the network toward remaining constant across temporal
      sequences of saccadic motions and covert attention shifts. We use a four-layer
      neural network model to perform the position-invariant extraction of local
      features and temporal integration of invariant presentations of local features in
      a bottom-up structure. We present results on both simulated data and real images
      to demonstrate that our network can acquire both position and attention shift
      invariance.

PMID- 15476603
TI  - Testing for and estimating latency effects for poisson and non-poisson spike
      trains.
AB  - Determining the variations in response latency of one or several neurons to a
      stimulus is of interest in different contexts. Two common problems concern
      correlating latency with a particular behavior, for example, the reaction time to
      a stimulus, and adjusting tools for detecting synchronization between two
      neurons. We use two such problems to illustrate the latency testing and
      estimation methods developed in this article. Our test for latencies is a formal
      statistical test that produces a p-value. It is applicable for Poisson and non
      Poisson spike trains via use of the bootstrap. Our estimation method is model
      free, it is fast and easy to implement, and its performance compares favorably to
      other methods currently available.

PMID- 15476604
TI  - Two-state membrane potential fluctuations driven by weak pairwise correlations.
AB  - Physiological experiments demonstrate the existence of weak pairwise correlations
      of neuronal activity in mammalian cortex (Singer, 1993). The functional
      implications of this correlated activity are hotly debated (Roskies et al.,
      1999). Nevertheless, it is generally considered a widespread feature of cortical
      dynamics. In recent years, another line of research has attracted great interest:
      the observation of a bimodal distribution of the membrane potential defining up
      states and down states at the single cell level (Wilson & Kawaguchi, 1996;
      Steriade, Contreras, & Amzica, 1994; Contreras & Steriade, 1995; Steriade, 2001).
      Here we use a theoretical approach to demonstrate that the latter phenomenon is a
      natural consequence of the former. In particular, we show that weak pairwise
      correlations of the inputs to a compartmental model of a layer V pyramidal cell
      can induce bimodality in its membrane potential. We show how this relationship
      can account for the observed increase of the power in the gamma-frequency band
      during up states, as well as the increase in the standard deviation and fraction
      of time spent in the depolarized state (Anderson, Lampl, Reichova, Carandini, &
      Ferster, 2000). In order to quantify the relationship between the correlation
      properties of a cortical network and the bistable dynamics of single neurons, we
      introduce a number of new indices. Subsequently, we demonstrate that a
      quantitative agreement with the experimental data can be achieved, introducing
      voltage-dependent mechanisms in our neuronal model such as Ca(2+)- and Ca(2+)
      dependent K(+) channels. In addition, we show that the up states and down states
      of the membrane potential are dependent on the dendritic morphology of cortical
      neurons. Furthermore, bringing together network and single cell dynamics under a
      unified view allows the direct transfer of results obtained in one context to the
      other and suggests a new experimental paradigm: the use of specific intracellular
      analysis as a powerful tool to reveal the properties of the correlation structure
      present in the network dynamics.

PMID- 15476605
TI  - On the uniqueness of loopy belief propagation fixed points.
AB  - We derive sufficient conditions for the uniqueness of loopy belief propagation
      fixed points. These conditions depend on both the structure of the graph and the
      strength of the potentials and naturally extend those for convexity of the Bethe
      free energy. We compare them with (a strengthened version of) conditions derived
      elsewhere for pairwise potentials. We discuss possible implications for
      convergent algorithms, as well as for other approximate free energies.

PMID- 15476606
TI  - Neural network uncertainty assessment using Bayesian statistics: a remote sensing
      application.
AB  - Neural network (NN) techniques have proved successful for many regression
      problems, in particular for remote sensing; however, uncertainty estimates are
      rarely provided. In this article, a Bayesian technique to evaluate uncertainties
      of the NN parameters (i.e., synaptic weights) is first presented. In contrast to
      more traditional approaches based on point estimation of the NN weights, we
      assess uncertainties on such estimates to monitor the robustness of the NN model.
      These theoretical developments are illustrated by applying them to the problem of
      retrieving surface skin temperature, microwave surface emissivities, and
      integrated water vapor content from a combined analysis of satellite microwave
      and infrared observations over land. The weight uncertainty estimates are then
      used to compute analytically the uncertainties in the network outputs (i.e.,
      error bars and correlation structure of these errors). Such quantities are very
      important for evaluating any application of an NN model. The uncertainties on the
      NN Jacobians are then considered in the third part of this article. Used for
      regression fitting, NN models can be used effectively to represent highly
      nonlinear, multivariate functions. In this situation, most emphasis is put on
      estimating the output errors, but almost no attention has been given to errors
      associated with the internal structure of the regression model. The complex
      structure of dependency inside the NN is the essence of the model, and assessing
      its quality, coherency, and physical character makes all the difference between a
      blackbox model with small output errors and a reliable, robust, and physically
      coherent model. Such dependency structures are described to the first order by
      the NN Jacobians: they indicate the sensitivity of one output with respect to the
      inputs of the model for given input data. We use a Monte Carlo integration
      procedure to estimate the robustness of the NN Jacobians. A regularization
      strategy based on principal component analysis is proposed to suppress the
      multicollinearities in order to make these Jacobians robust and physically
      meaningful.

PMID- 15476607
TI  - Principal components analysis competitive learning.
AB  - We present a new neural model that extends the classical competitive learning by
      performing a principal components analysis (PCA) at each neuron. This model
      represents an improvement with respect to known local PCA methods, because it is
      not needed to present the entire data set to the network on each computing step.
      This allows a fast execution while retaining the dimensionality-reduction
      properties of the PCA. Furthermore, every neuron is able to modify its behavior
      to adapt to the local dimensionality of the input distribution. Hence, our model
      has a dimensionality estimation capability. The experimental results we present
      show the dimensionality-reduction capabilities of the model with multisensor
      images.

PMID- 15476608
TI  - Predictors of and outcomes of early thrombosis following balloon angioplasty
      versus primary stenting in acute myocardial infarction and usefulness of
      abciximab (the CADILLAC trial).
AB  - We sought to identify the predictors and clinical outcomes of early thrombosis
      after primary angioplasty and stenting for acute myocardial infarction (AMI).
      Little is known about the correlates and prognosis of acute and subacute
      thromboses after percutaneous coronary intervention (PCI) for AMI. We therefore
      studied the frequency, clinical determinants, and implications of early
      thrombosis in a large trial of patients who had primary PCI. In the Controlled
      Abciximab and Device Investigation to Lower Late Angioplasty Complications trial,
      2,082 patients who had AMI were randomized in a 2 x 2 factorial design to primary
      stenting or to balloon angioplasty, each with and without abciximab. Early
      thrombosis occurred in 19 patients (0.9%) at a median of 2 days (range 0 to 23).
      Maximal balloon diameter was smaller, and aneurysmal and bifurcation lesions were
      more prevalent in the group with early thrombosis. Early thrombosis occurred in
      0.4% of patients who had been randomized to receive abciximab versus 1.5% of
      control patients (p <0.01) and in 0.5% of patients who had been randomized to
      undergo stenting versus 1.4% of those who underwent balloon angioplasty (p =
      0.04). By multivariate analysis, abciximab use was an independent predictor of no
      thrombosis (hazard ratio 0.27, 95% confidence interval 0.09 to 0.86, p = 0.026).
      Within 30 days, 5.3% of patients who had early thrombosis died, 32.9% developed
      reinfarction, and 89.5% required repeat target vessel revascularization
      (including bypass surgery in 11.1%). As a result, patients who had versus those
      who did not have early thrombosis had markedly higher rates of major adverse
      cardiac events at 30 days (94.7% vs 5.0%, p <0.0001) and at 1 year (94.7% vs
      16.9%, p <0.0001). Patients who develop early thrombosis after primary PCI have a
      very high rate of major adverse cardiac events, including death and reinfarction,
      and usually require repeat coronary angioplasty or surgery for management.
      Complex baseline angiographic morphology and smaller maximal balloon diameter are
      predictors of early thrombosis after primary PCI for AMI. The incidence of early
      thrombosis after primary angioplasty and stenting is decreased by abciximab use.

PMID- 15476609
TI  - Long-term prognosis of patients having acute myocardial infarction when </=40
      years of age.
AB  - Data on the long-term prognosis of acute myocardial infarction (AMI) in young
      patients are limited. This study investigated long-term survival and risk
      predictors in a series of 108 consecutive patients </=40 years old who
      represented 4% of 2,644 patients who presented with AMI at a single center
      between June 1986 and April 1992. Four patients died soon after admission. The
      overall mortality rate of the 104 survivors was 25.5% at 15 years. The mortality
      rate was higher in patients who had type 1 diabetes mellitus (p = 0.01), long
      term excessive alcohol intake (p = 0.035), peripheral arterial disease (p =
      0.004), previous AMI (p = 0.04), anterior AMI (p = 0.01), and depressed left
      ventricular ejection fraction (p <0.0001). Cumulative survival rates (Kaplan
      Meier analysis) at 1, 5, 10, and 15 years were 99%, 95%, 86%, and 75%,
      respectively. Event-free survival rates (death, AMI, coronary intervention,
      severe angina pectoris, malignant arrhythmias, and congestive heart failure) at
      the same times were 88%, 76%, 60%, and 43%, respectively. The strongest
      independent predictors of the long-term mortality rate were ejection fraction
      </=45% (odds ratio 4.4, 95% confidence interval 1.6 to 12.4, p <0.001) and
      peripheral arterial disease (odds ratio 45.9, 95% confidence interval 3.79 to
      555, p <0.0001). These data suggest that the long-term prognosis and functional
      status of young patients who have AMI are not benign, especially when ejection
      fraction is decreased or peripheral atherosclerotic disease is present.

PMID- 15476610
TI  - Prognostic usefulness of plasma monocyte/macrophage and T-lymphocyte activation
      markers in patients with acute coronary syndromes.
AB  - Macrophages and T lymphocytes accumulate and are activated in atherosclerotic
      plaques. We tested the hypothesis that plasma levels of the monocyte/macrophage
      and T-lymphocyte activation markers, monocyte chemoattractant protein-1 (MCP-1)
      and soluble interleukin-2 receptor (sIL-2r), respectively, can be used in acute
      coronary syndrome classification and risk prediction. Blood samples were
      collected at hospital admissions of 183 patients who had ischemic chest pain. Of
      these, 59 had acute myocardial infarction, 60 had unstable angina, and 64 had
      angina pectoris. No significant differences in the levels or proportions of
      subjects with increased levels of MCP-1 or sIL-2r were found across groups.
      During a mean follow-up of 13 months, 117 patients (64%) had a study end point
      (i.e., cardiac death, recurrent myocardial infarction, unstable angina, or
      revascularization). Increased levels (above median) of MCP-1 and sIL-2r were
      associated with increased risk, with odds ratios of 1.85 (95% confidence interval
      0.92 to 3.73, p = 0.08) and 2.34 (95% confidence interval 1.16 to 4.71, p <0.02),
      respectively. In summary, in this unselected patient population with a very high
      rate of coronary events during follow-up, increased plasma levels of MCP-1 and
      sIL-2r were helpful for predicting new coronary events.

PMID- 15476611
TI  - Gender differences in the value of ST-segment depression during adenosine stress
      testing.
AB  - Previous studies have suggested that ST-segment depression with adenosine
      myocardial perfusion imaging (MPI) may be a marker of significant coronary artery
      disease (CAD). It is unclear if the significance of ST depression differs between
      men and women. We investigated the diagnostic accuracy of ST-segment depression
      with adenosine radionuclide MPI as a marker of significant CAD in men and women.
      Consecutive patients who had angina or suspected CAD and underwent an adenosine
      stress test and subsequent angiography were retrospectively analyzed. The
      inclusion criteria were met by 959 patients. Mean age was 64 +/- 11 years, and
      43% were women. ST depression occurred in 7.6% of the cohort and more often in
      women (64% women vs 36% men, p <0.001). Among men and women, patients with ST
      segment depression had a significantly higher peak rate-pressure product, more
      chest pain, and a higher ejection fraction in response to the adenosine infusion
      compared with those without ST-segment depression. ST-segment depression occurred
      more often in the presence of stenotic lesions (>/=50% and >/=70%), and left main
      or 3-vessel disease, regardless of gender. Transient ischemic dilation occurred
      more often in men with ST-segment depression. The logistic regression analysis
      demonstrated that the only significant predictors of left main or 3-vessel CAD
      were gender, an abnormal result on MPI, transient ischemic dilation, and ST
      segment depression. In conclusion, ST-segment depression during adenosine MPI is
      an important marker of angiographically significant CAD in men and women. The
      presence of ST-segment depression is associated with left main disease and 3
      vessel CAD.

PMID- 15476612
TI  - Comparison of outcomes of white versus black patients hospitalized with heart
      failure and preserved ejection fraction.
AB  - Black patients who have heart failure (HF) may have a larger proportion of HF
      with preserved ejection fraction (PEF) than white patients because of the greater
      prevalence and severity of hypertension and left ventricular hypertrophy in
      blacks. However, studies have not systematically evaluated differences by race in
      patients who have HF-PEF compared with those who have systolic HF (SHF).
      Therefore, we examined baseline characteristics and long-term outcomes in
      patients who had HF-PEF compared with those who had SHF, with an emphasis on
      variation by race, in a biracial cohort of patients treated within the Veterans
      Health Administration health care system. In a cohort of 448 patients (192 blacks
      and 256 whites) hospitalized with HF, 27% had HF-PEF. The proportion of HF-PEF
      was similar in black (25%) and white (29%) patients (p = 0.4). Among patients who
      had SHF, black patients were younger, had lower prevalences of atrial
      fibrillation and diabetes, and had less co-morbidities than white patients,
      whereas there were no significant differences in these variables by race in
      patients who had HF-PEF. However, among patients who had SHF or HF-PEF, blacks
      had a lower prevalence of coronary disease, higher systolic and diastolic blood
      pressures, and higher serum levels of creatinine than white patients. In
      addition, mortality and readmission rates for HF did not differ by race among
      patients who had HF-PEF. Overall, patients who had HF-PEF had a high morbidity
      rate (30% patients were readmitted for HF in </=6 months) and a high mortality
      rate (44% at 3 years), despite the use of angiotensin-converting enzyme
      inhibitors by 66% of patients at discharge. This underscores the importance of
      evaluating other agents for the treatment of patients who have HF-PEF.

PMID- 15476613
TI  - Prognostic significance of newly acquired bundle branch block after aortic valve
      replacement.
AB  - There is controversy concerning the prognostic significance of conduction delays
      that occur after aortic valve replacement (AVR). We retrospectively reviewed 389
      consecutive patients who underwent AVR at our institution between April 1995 and
      March 1997. Adverse events were defined as the occurrence of complete
      atrioventricular block, syncope, or sudden cardiac death. Among 262 patients
      included in our database, 31 (11.8%) had a preoperative bundle branch block (BBB)
      and 41 (15.6%) developed new BBB postoperatively. At a mean follow-up of 54
      months, the event rate was 1.6% (3 of 190) in patients with no BBB versus 17% (7
      of 41, p = 0.0004) in patients who developed new BBB after surgery. There were 4
      events (4 of 15 = 26.6%, p = 0.0006) in patients who developed new left BBB and 3
      (3 of 26, 11.5%, p = 0.02) in those who developed new right BBB after AVR. There
      was also an increased adverse event rate in patients who had preoperative BBB (3
      of 31, 9.7%, p = 0.037). By multivariate analysis, a new and persistent BBB
      acquired after surgery was the only independent predictor of adverse events
      during follow-up (odds ratio 8.85, p = 0.0004). The highest event rate was seen
      in patients who developed new left BBB and left axis deviation after surgery.
      Most events occurred during the first year of follow-up. A new and persistent BBB
      acquired after AVR is associated with an increased adverse event rate. This
      finding suggests that early prophylactic pacemaker implantation should be
      considered in these patients.

PMID- 15476614
TI  - Comparison of results of percutaneous closure of patent foramen ovale for
      paradoxical embolism in patients with versus without thrombophilia.
AB  - We investigated the efficacy of transcatheter patent foramen ovale (PFO) closure
      to prevent recurrent cerebral ischemic events in patients who did and those who
      did not have thrombophilia. Patients who have a PFO and an associated
      thrombophilia may have an increased risk of cerebral ischemic events. Seventy-two
      consecutive patients (mean age 42 +/- 13 years) underwent percutaneous PFO
      closure because of a cerebral stroke (51%) or a transient ischemic attack (49%).
      A thrombophilia was found in 20 patients (28%). A large right-to-left shunt
      through the PFO was found in 44 patients (61%) and an atrial septal aneurysm was
      found in 39 (54%). After the first event, 18 of 20 patients (90%) with a
      thrombophilia received oral anticoagulation. Before closure, patients who had a
      thrombophilia also had a higher rate of recurrences than patients who did not (p
      <0.0001), despite a similar follow-up (p = 0.14) and regardless of shunt entity
      (p = 0.59), presence of an atrial septal aneurysm (p = 0.98), and a prevalence of
      cardiovascular risk factors (p = 0.44). PFO closure was successful in all
      patients. Five patients (8%) had a residual shunt at 6 months. At 20 +/- 11
      months after PFO closure, 3 recurrent events occurred (4%), and the recurrence
      rate was similar in patients who did and those who did not have a thrombophilia
      (p = 0.25). Thus, in patients who have a cryptogenic stroke, the association of a
      PFO with a thrombophilia significantly increases the risk of recurrences. Thus,
      transcatheter PFO closure is effective for preventing recurrences in patients who
      have a thrombophilia.

PMID- 15476615
TI  - Value of immediate postoperative electrocardiogram to update risk stratification
      after major noncardiac surgery.
AB  - Current consensus guidelines recommend postoperative electrocardiographic
      surveillance only in patients at relatively high risk of postoperative major
      cardiac complications, but the usefulness of electrocardiograms after major
      noncardiac surgery is unknown. We prospectively studied 3,570 patients who
      underwent major noncardiac procedures and had electrocardiograms performed in the
      recovery room. Rates of major cardiac complications (acute myocardial infarction,
      pulmonary edema, ventricular fibrillation or primary cardiac arrest, and complete
      heart block) were higher in patients who had new postoperative
      electrocardiographic abnormalities consistent with ischemia (ST-T elevation or
      depression or T-wave abnormalities compatible with ischemia) compared with those
      without ischemia (6.7% vs 1.9%, p <0.001). Multivariate analysis, after adjusting
      for pre- and intraoperative clinical data, indicated that the presence of
      ischemia on the immediate postoperative electrocardiogram was an independent
      predictor of major cardiac complications (odds ratio 2.2, 95% confidence interval
      1.2 to 3.9, p <0.01). When patients were stratified by a preoperative Revised
      Cardiac Risk Index, ischemia on the immediate postoperative electrocardiogram
      identified patients with a higher risk of major cardiac complications in low- and
      high-risk subsets (odds ratio 4.9, 95% confidence interval 1.6 to 15 in lower
      risk patients; odds ratio 2.0, 95% confidence interval 1.0 to 3.7 in higher risk
      patients). We conclude that the immediate postoperative electrocardiogram is a
      valuable tool to adjust risk stratification, even in patients who have lower
      risks when undergoing noncardiac surgery.

PMID- 15476616
TI  - Impact of anemia on outcomes of patients undergoing percutaneous coronary
      interventions.
AB  - Of 6,929 consecutive patients who were treated with percutaneous coronary
      intervention, 1,708 (24.6%) had anemia according to criteria of the World Health
      Organization. Compared with patients who did not have anemia, those who did have
      anemia were older, more frequently women and African-American, had a smaller body
      mass index, and higher frequencies of cardiovascular risk factors and co-morbid
      conditions. Patients who had anemia compared with those who did not have anemia
      had significantly (p <0.0001) higher mortality rates during hospitalization (1.9%
      vs 0.4%) and at 1 year (12.8% vs 3.5%). After adjustment for potential
      confounders, baseline hematocrit remained a significant predictor of a 1-year
      mortality rate (hazard ratio 0.93 per 1% increase in hematocrit, 95% confidence
      interval 0.91 to 0.95).

PMID- 15476617
TI  - Usefulness of hyperglycemia in predicting renal and myocardial injury in patients
      with diabetes mellitus undergoing percutaneous coronary intervention.
AB  - A retrospective analysis of 165 patients who had diabetes mellitus and underwent
      percutaneous coronary intervention (PCI) between 1998 and 2003 demonstrated that
      those whose plasma glucose levels were >/=200 mg/dl before PCI exhibited greater
      creatine phosphokinase release and serum creatinine increases after PCI. These
      observations identified hyperglycemia as a potentially modifiable mediator of
      myocardial and renal injuries in patients who have diabetes and have undergone
      PCI.

PMID- 15476618
TI  - Influence of admission and discharge aspirin use on survival after primary
      coronary angioplasty for acute myocardial infarction.
AB  - We examined the effect of aspirin use at the time of admission and discharge from
      a large-scale, prospective multicenter trial of patients who had been treated
      with primary percutaneous coronary intervention in acute myocardial infarction.

PMID- 15476619
TI  - Usefulness of coronary flow reserve immediately after primary coronary stenting
      in predicting wall motion recovery in patients with anterior wall acute
      myocardial infarction.
AB  - This study examined whether coronary flow reserve (CFR) measured immediately
      after primary coronary stenting could predict wall motion recovery in patients
      who have acute myocardial infarction. CFR significantly correlated with the
      change of wall motion score (r = 0.68, p <0.0001), and the optimal cut-off value
      of CFR for predicting wall motion recovery was 1.4 (sensitivity 85%, specificity
      94%).

PMID- 15476620
TI  - Mechanism of coronary artery restenosis after stenting for acute myocardial
      infarction.
AB  - In this intravascular ultrasound study, the mechanism of restenosis after
      stenting in acute myocardial infarction (AMI) was investigated in 33 patients 6
      months after primary coronary intervention for AMI. Restenosis after stenting for
      AMI was primarily caused by stent underexpansion, not by neointima formation.

PMID- 15476621
TI  - Comparison of temporary occlusion and aspiration system versus the conventional
      method during coronary stenting for acute myocardial infarction.
AB  - This study evaluated the effects of the temporary occlusion and aspiration device
      GuardWire on percutaneous coronary intervention for acute myocardial infarction.
      This device brought about a significant reduction in the no-reflow phenomenon and
      improvement in ST resolution compared with conventional percutaneous coronary
      intervention.

PMID- 15476622
TI  - Matrix metalloproteinase-1 promoter polymorphisms and changes in left ventricular
      volume following acute myocardial infarction.
AB  - The relation between matrix metalloproteinase-1 promoter genotype and remodeling
      was studied in 42 patients after their first acute myocardial infarctions.
      Patients possessing 2 GG alleles were at increased risk for remodeling compared
      with homozygotes for the G allele and heterozygotes possessing 1 G and 1 GG
      allele.

PMID- 15476623
TI  - Bivalirudin versus heparin as an antithrombotic agent in patients treated with a
      sirolimus-eluting stent.
AB  - Bivalirudin (Angiomax) is increasingly used as a substitute for heparin in a
      variety of percutaneous coronary interventions. This retrospective, observational
      study aimed to evaluate the efficacy and safety of bivalirudin compared with
      heparin as an antithrombotic regimen in patients treated with sirolimus-eluting
      stents (Cypher) and found that bivalirudin is clinically safe and feasible, with
      fewer vascular and ischemic complications compared with heparin.

PMID- 15476624
TI  - Effect of abciximab-coated stent on in-stent intimal hyperplasia in human
      coronary arteries.
AB  - The investigators tested whether abciximab-coated stents prevent neointimal
      hyperplasia (NIH) formation in coronary de novo lesions. Abciximab-coated stents
      were compared with control stents. All patients underwent follow-up coronary
      angiography and intravascular ultrasound (IVUS). All stents were successfully
      deployed, and patients were discharged home without clinical events. At follow-up
      coronary angiography, the restenosis rate and late loss were 14% and 0.33 +/-
      0.28 mm in the abciximab-coated stent group and 28.6% and 0.64 +/- 0.32 mm in the
      control stent group (p = 0.099 and p = 0.014, respectively). At follow-up IVUS,
      the intrastent luminal area and intrastent NIH area were 5.7 +/- 1.6 and 2.0 +/-
      1.6 mm(2), respectively, in the abciximab-coated stent group and 4.2 +/- 0.8 and
      3.4 +/- 1.7 mm(2), respectively, in the control stent group (p = 0.001 and p =
      0.001, respectively). Abciximab-coated stents are feasible and significantly
      inhibit NIH, with potential therapeutic benefit in preventing stent restenosis.

PMID- 15476625
TI  - Usefulness of temporary left ventricular pacing through the coronary sinus as an
      adjunct to transfemoral percutaneous coronary intervention.
AB  - In 10 patients who underwent percutaneous coronary intervention involving the
      right coronary artery, a new procedure for adjunctive temporary transfemoral
      pacing of the left ventricle through the coronary sinus was tested. The procedure
      was successful in 8 of 10 patients and could be performed in <5 minutes by
      experienced operators and supervised cardiology fellows.

PMID- 15476626
TI  - Effectiveness of percutaneous coronary interventions in nonagenarians.
AB  - Data on percutaneous coronary intervention (PCI) in nonagenarians are very
      scarce. The investigators present a series of 26 nonagenarians who underwent PCI
      (29 lesions, 1.1 +/- 0.3 per patient). Most (96%) had acute coronary syndrome at
      presentation, 27% underwent primary PCI for acute myocardial infarctions, and 54%
      had multivessel disease. Angiographically successful results were obtained in 24
      patients (92%), and coronary stents were used in 81%. Five patients (19%) died
      during hospitalization. In-hospital mortality was significantly greater in
      patients with Killip class III or IV at presentation (100% vs 9%, p = 0.001), in
      those in whom the procedure was a primary PCI for acute myocardial infarction
      (57% vs 5%, p = 0.010), and in the presence of angiographic failure (100% vs 13%,
      p = 0.031). In-hospital mortality was 0% after excluding patients in cardiogenic
      shock and those with primary PCI. Thus, most nonagenarians who undergo PCI have a
      high-risk profile. However, PCI achieves a successful angiographic result in most
      patients. Mortality is high but concentrated in patients in cardiogenic shock and
      with primary angioplasty as PCI.

PMID- 15476627
TI  - Two-year outcomes of repeated brachytherapy in patients with restenosis after
      intracoronary radiation therapy.
AB  - This study compared the 2-year outcomes of repeat brachytherapy (n = 10) and
      conventional percutaneous intervention (n = 14) in patients with restenosis after
      intracoronary brachytherapy with a rhenium-188-filled balloon system. The short
      term target lesion revascularization rate was significantly lower in the repeat
      brachytherapy group (0% vs 36%, p = 0.038), and additional target lesion
      revascularization was required in 2 patients with repeat brachytherapy during 2
      year follow-up. There were no vascular complications related to repeat
      brachytherapy.

PMID- 15476628
TI  - Assessing the prognostic value of coronary endothelial function in patients
      referred for a first coronary angiogram.
AB  - At present, the value of endothelial function as a prognostic tool has been
      evaluated only in selected groups of patients with mild or minor coronary artery
      disease, not in the complete spectrum of patients presenting with angina. The
      objective of this study was to evaluate whether endothelium-dependent
      vasodilation of the coronary arteries in response to acetylcholine infusion as a
      marker of endothelial function would have prognostic value in patients referred
      for a first coronary angiogram. The data suggest that endothelial function
      assessment does not contribute to the prediction of outcomes in patients referred
      for a first coronary angiogram.

PMID- 15476629
TI  - Vascular remodeling and plaque composition between focal and diffuse coronary
      lesions assessed by intravascular ultrasound.
AB  - Coronary remodeling and plaque composition were compared between focal and
      diffuse coronary lesions. Negative remodeling and fibrous and calcified plaque
      compositions contribute to stenosis development in diffuse lesions more
      frequently than in focal lesions.

PMID- 15476630
TI  - Effect of edaravone, a novel free radical scavenger, on endothelium-dependent
      vasodilation in smokers.
AB  - The forearm blood flow (FBF) responses to acetylcholine and to sodium
      nitroprusside were evaluated before and after administration of edaravone in 10
      smokers and 10 nonsmokers. FBF response to acetylcholine was lower in smokers
      than in nonsmokers. The vasodilatory effects of sodium nitroprusside were similar
      in both groups. Co-infusion of edaravone increased the FBF response to
      acetylcholine in smokers, but did not affect the FBF response to acetylcholine in
      nonsmokers. The administration of N(G)-monomethyl-l-arginine abolished edaravone
      induced augmentation of the FBF response to acetylcholine in smokers. The
      antioxidative agent edaravone increases nitric oxide mediated vasodilation
      through a decrease in oxidative stress.

PMID- 15476631
TI  - Feasibility and safety of noninvasive pacemaker stress echocardiography with
      externally triggered stimulation.
AB  - The aim of this study was to assess the feasibility and safety of stress
      echocardiography by triggering an implanted pacemaker through an external
      stimulator. The implanted pacemaker was set in triggered mode with unipolar
      sensitivity of <2 mV. The external stimulator, connected to 2 skin electrodes,
      tracked the implanted pacemaker at increasing rates. Fifteen patients (mean age
      65 +/- 8 years) with suspected coronary artery disease entered the study, and
      complete tests were performed in all patients. No adverse effects were reported.
      The method of externally triggered stimulation is feasible, safe, and allows a
      diagnosis in every patient with a pacemaker without additional cost.

PMID- 15476632
TI  - Effect of losartan versus atenolol on aortic valve sclerosis (a LIFE substudy).
AB  - Neither losartan- nor atenolol-based antihypertensive regimens could prevent the
      progression of aortic valve (AV) sclerosis in elderly, high-risk hypertensive
      patients, and the regression of AV sclerosis did not translate into reduced
      cardiovascular risk.

PMID- 15476633
TI  - Usefulness of optical coherent reflectometry with guided radiofrequency energy to
      treat chronic total occlusions in peripheral arteries (the GRIP trial).
AB  - Optical coherent reflectometry, a forward-looking, fiberoptic-guided device was
      used in 72 patients to direct radiofrequency energy across the central
      intraluminal portion of 75 chronic total occlusions in peripheral arteries
      (iliac, femoral, and popliteal) that failed attempts with conventional
      guidewires. The system was successful in crossing 76% of the chronic total
      occlusions with no clinical perforations or distal embolizations, and
      complications consisted of a single dissection greater than or equal to grade C.

PMID- 15476634
TI  - Relation between epicardial adipose tissue and left ventricular mass.
AB  - Visceral adiposity is a cardiovascular risk factor of growing interest. This
      study sought to evaluate the hypothesis of a relation between epicardial adipose
      tissue, the visceral adipose tissue deposited around the heart, and left
      ventricular morphology in healthy subjects with a wide range of adiposity. We
      found for the first time that an increase in epicardial fat is significantly
      related to an increase in left ventricular mass.

PMID- 15476635
TI  - Tissue Doppler imaging of the right and left ventricle in severe obesity (body
      mass index >35 kg/m2).
AB  - We investigated right and left heart function in 51 patients with a body mass
      index of >35 kg/m(2) who underwent evaluation for gastric bypass surgery using
      standard Doppler echocardiography and color tissue Doppler imaging. Left atrial
      diameter (3.7 +/- 0.5 vs 3.3 +/- 0.4 cm, p <0.001), left ventricular end
      diastolic diameter (5.0 +/- 0.6 vs 4.5 +/- 0.4 cm, p <0.001), and left
      ventricular mass index (119 +/- 49 vs 76 +/- 26 g/m, p <0.001) were increased in
      patients with severe obesity. Early diastolic mitral annular velocity (7.5 +/-
      2.1 vs 9.6 +/- 3.0 cm/s, p <0.001), early diastolic/late diastolic mitral annular
      velocity ratio (1.38 +/- 0.6 vs 1.94 +/- 1.3, p = 0.007), early diastolic
      tricuspid annular velocity (7.8 +/- 2.6 vs 9.5 +/- 2.4 cm/s, p = 0.002), early
      diastolic/late diastolic tricuspid annular velocity ratio (0.9 +/- 0.36 vs 1.1 +/
      0.4, p = 0.048), and mitral annular systolic velocity (5.7 +/- 1.3 vs 6.5 +/-
      1.5 cm/s, p = 0.012) were significantly lower in obese patients. Early diastolic
      mitral inflow/mitral annular velocity ratio was increased in the obese (13.5 +/-
      4.7 vs 9.1 +/- 3.6, p <0.001). Tricuspid annular systolic velocities did not
      differ.

PMID- 15476636
TI  - Outcome and complications of retrievable inferior vena cava filters.
AB  - The results and risks of retrievable inferior vena cava filters were reviewed.
      Systematic review identified 6 prospective case series with broad ranges of
      indications for filters. In these case series, 4 different types of retrievable
      filters were inserted in 284 patients. The longest reported duration of insertion
      was 134 days. Among patients in whom percutaneous removal of the filter was
      attempted, the filter was successfully removed in 144 of 159 (91%). Surgery was
      necessary to remove the filter from 1 patient (1%), and filters could not be
      removed because of large trapped thrombi in 14 patients (9%).

PMID- 15476637
TI  - Effect of chronic kidney disease on outcomes after carotid artery stenting.
AB  - We performed a single-center retrospective analysis evaluating the effect of
      chronic kidney disease among patients who underwent carotid artery stenting. The
      presence of chronic kidney disease is associated with higher periprocedural and 6
      month death, stroke, or myocardial infarction after carotid artery stenting.

PMID- 15476638
TI  - Quantitative assessment of right ventricular geometric remodeling in pulmonary
      hypertension secondary to left-sided heart disease using real-time three
      dimensional echocardiography.
AB  - We assessed right ventricular (RV) geometric remodeling quantitatively in
      patients with chronic pulmonary hypertension (PH) secondary to left-sided heart
      disease using real-time 3-dimensional echocardiography by comparing segmental and
      total volumes to that in normal subjects. The comparison result revealed that RV
      geometric remodeling in the PH group mainly occurred at the basal, mid-basal, and
      mid-segments. Total RV end-diastolic and end-systolic volumes in the PH group
      were significantly larger than that in normal subjects.

PMID- 15476639
TI  - Which echocardiographic Doppler left ventricular diastolic function measurements
      are most feasible in the clinical echocardiographic laboratory?
AB  - Numerous measures of left ventricular diastolic function are currently in
      clinical use. To determine which echo-Doppler left ventricular diastolic function
      measurements are most feasible in the clinical echocardiographic laboratory, the
      success rate, recording time taken by the sonographer, and inter-reader
      variability were calculated for transmitral valve inflow, pulmonary vein flow,
      tissue Doppler imaging, and color M-mode flow propagation velocity in 80
      inpatients.

PMID- 15476640
TI  - Reactivation of cardiac Chagas' disease in acquired immune deficiency syndrome.
AB  - We report the case of a 29-year-old man who developed acute congestive heart
      failure secondary to cardiac Chagas' disease in the setting of Trypanosoma cruzi
      reactivation by acquired immune deficiency syndrome.

PMID- 15476641
TI  - Rate control in AFFIRM: considerations about the clinical implications.

PMID- 15476642
TI  - Usefulness of statins in protecting against atrial fibrillation.

PMID- 15476643
TI  - Impact of levosimendan treatment on chronic heart failure.

PMID- 15476646
TI  - Robotic technology in surgery: past, present, and future.
AB  - It has been nearly 20 years since the first appearance of robotics in the
      operating room. In that time, much progress has been made in integrating robotic
      technologies with surgical instrumentation, as evidenced by the many thousands of
      successful robot-assisted cases. However, to build on past success and to fully
      leverage the potential of surgical robotics in the future, it is essential to
      maximize a shared understanding and communication among surgeons, engineers,
      entrepreneurs, and healthcare administrators. This article provides an
      introduction to medical robotic technologies, develops a possible taxonomy,
      reviews the evolution of a surgical robot, and discusses future prospects for
      innovation. Robotic surgery has demonstrated some clear benefits. It remains to
      be seen where these benefits will outweigh the associated costs over the long
      term. In the future, surgical robots should be smaller, less expensive, easier to
      operate, and should seamlessly integrate emerging technologies from a number of
      different fields. Such advances will enable continued progress in surgical
      instrumentation and, ultimately, surgical care.

PMID- 15476647
TI  - Building a surgical robotics program.
AB  - Building a strong institutional robotics program requires commitment from
      administrative and clinical departments. Here we present issues to be considered
      when developing such a program, including development of a pathway for
      introduction of the technology into patient care, team recruitment, creation of
      an objective-based curriculum, multispecialty training, and proper patient
      selection.

PMID- 15476648
TI  - Robotic abdominal surgery.
AB  - As a whole, abdominal surgeons possess excellent videoendoscopic surgical skills.
      However, the limitations of laparoscopy-such as reduced range of motion and
      instrument dexterity and 2-dimensional view of the operative field-have inspired
      even the most accomplished laparoscopists to investigate the potential of
      surgical robotics to broaden their application of the minimally invasive surgery
      paradigm. This review discusses data obtained from articles indexed in the
      MEDLINE database written in English and mapped to the following key words:
      "surgical robotics," "robotic surgery," "robotics," "computer-assisted surgery,"
      "da Vinci," "Zeus," "fundoplication," "morbid obesity," "hepatectomy,"
      "pancreatectomy," "small intestine," "splenectomy," "colectomy," "adrenalectomy,"
      and "pediatric surgery." A limited subset of 387 publications was reviewed to
      determine article relevance to abdominal robotic surgery. Particular emphasis was
      placed on reports that limited their discussion to human applications and
      surgical outcomes. Included are comments about the initial 202 robotic abdominal
      surgery cases performed at Johns Hopkins University Hospital (Baltimore, MD) from
      August 2000 to January 2004. Surgical robotic systems are being used to apply
      laparoscopy to the surgical treatment of diseases in virtually every abdominal
      organ. Procedures demanding superior visualization or requiring complex
      reconstruction necessitating extensive suturing obtain the greatest benefit from
      robotics over conventional laparoscopy. Whereas advanced surgical robotic systems
      offer the promise of a unique combination of advantages over open and
      conventional laparoscopic approaches, clinical data demonstrating improved
      outcomes are lacking for robotic surgical applications within the abdomen.
      Outcomes data for surgical robotics are essential given the exorbitant costs
      associated with the use of these tools.

PMID- 15476649
TI  - Robot-assisted pediatric surgery.
AB  - Computer-enhanced robotic surgical systems have been increasingly used to
      facilitate complex minimal access surgical procedures. In adult patients, such
      systems have been used to perform a wide variety of operations including coronary
      artery bypass grafting, mitral valve repair, Roux-en-Y gastric bypass, colon
      resection, nephrectomy, and radical prostatectomy. In the field of pediatric
      surgery, the experience with robotic surgical systems has been more limited.
      However, with improvements in robotic technology, interest and experience with
      robotic pediatric surgery have grown rapidly. The purpose of this article is to
      review the current experimental and clinical literature regarding the use of
      robotic surgical systems in the pediatric patient population.

PMID- 15476650
TI  - Robotically assisted bariatric surgery.
AB  - Obesity is a serious health problem in the United States today, and surgical
      treatment is recognized as long-term effective therapy. Minimally invasive
      techniques are becoming the "gold standard" approach to the treatment of disease,
      and robotic surgery has the potential to advance the use and development of
      minimally invasive procedures. In this article, we report our experience using
      robotically assisted technology to perform bariatric surgery. From mid 2002 to
      early 2004, 110 robotically assisted Roux-en-Y gastric bypass and 32 robotically
      assisted gastric banding procedures were performed at our institution. The mean
      preoperative body mass index was 46 for the patients receiving Roux-en-Y gastric
      bypass and 49 for the patients receiving gastric banding. The mean length of stay
      was 2.1 days and 1 day for patients in the 2 respective groups. There were 3
      strictures in the Roux-en-Y group and 1 marginal ulcer in the gastric banding
      group; no leaks were observed in any patients in either group. There was 1
      conversion to a laparoscopic procedure in the Roux-en-Y gastric bypass group. We
      conclude that robotically assisted bariatric surgery will allow more surgeons to
      offer patients the same safety and successful outcomes currently available
      through open techniques but without the significant morbidities of large surgical
      wounds.

PMID- 15476651
TI  - Robotically assisted donor nephrectomy for kidney transplantation.
AB  - The application of minimally invasive techniques in the field of transplant
      surgery is expanding the number of living-related donor nephrectomies. In 2003,
      the number of living kidney donors exceeded the number of cadaveric donors. The
      laparoscopic techniques already have been described extensively. Our experience
      with robotic donor nephrectomy began in October 2000. In this article, we
      describe the surgical technique for living-related donor nephrectomies using
      robotic technology (computer-enhanced surgery), as well as the most important
      considerations regarding the pre- and postoperative management of this group of
      patients.

PMID- 15476652
TI  - Gynecologic use of robotically assisted laparoscopy: Sacrocolpopexy for the
      treatment of high-grade vaginal vault prolapse.
AB  - Transabdominal sacrocolpopexy is an excellent treatment option for patients with
      high-grade vaginal vault prolapse, with long-term success rates ranging from 93%
      to 99%. However, it is associated with increased morbidity compared with vaginal
      repairs. In this article, we describe a novel minimally invasive technique of
      vaginal vault prolapse repair and present our initial experience. The surgical
      technique involves placement of 4 laparoscopic ports, 3 for the surgical robot
      and 1 for the assistant. A prolene mesh is then attached to the sacral promontory
      and to the vaginal apex using nonabsorbable expanded polytetrafluoroethylene
      sutures. At the end of the case, the mesh material is covered by the peritoneum.
      A total of 20 patients underwent a robot-assisted laparoscopic sacrocolpopexy at
      our institution in the past 18 months for severe symptomatic vaginal vault
      prolapse; 8 of the 20 (40%) underwent a concomitant anti-incontinence procedure.
      Mean follow-up was 5.1 (range, 1-12) months and mean age was 66 (range, 47-82)
      years. The mean total operative time was 3.2 (range, 2.25-4.75) hours. Of these
      patients, 1 was converted to an open procedure secondary to unfavorable anatomy.
      All but 1 patient, who left on postoperative day 2, were discharged from the
      hospital after an overnight stay. Complications were limited to mild port-site
      infections in 2 patients, which resolved with oral antibiotic therapy. Recurrent
      grade 3 rectocele developed in 1 patient, but there was no evidence of cystocele
      or enterocele. Significant incontinence (>1 pad/day) was present in 2 patients.
      All 18 patients reported being satisfied with the outcome of their surgery and
      all 10 would recommend it to a friend. This novel technique for vaginal vault
      prolapse repair combines the advantages of open sacrocolpopexy with the decreased
      morbidity and improved cosmesis of laparoscopic surgery. It is associated with
      decreased hospital stay, low complication and conversion rates, and high rates of
      patient satisfaction. Although our early experience is encouraging, long-term
      data are needed to confirm these findings and establish longevity of the repair.

PMID- 15476653
TI  - Robotics in vascular surgery.
AB  - The procedure for surgical correction of aortic disease has gone relatively
      unchanged over the last 50 years, requiring a xiphoid pubic incision as well as
      shifting of the abdominal viscera. These maneuvers produce significant
      pathophysiologic changes that consequently affect intraoperative and
      postoperative care and recovery. In approaching minimally invasive aortic
      surgery, advances in computer-enhanced technology have the potential to
      revolutionize aortic surgery and improve patient safety. A MEDLINE search
      specific to robotic aortic vascular procedures was performed and produced 7
      articles (3 animal model and 4 clinical application). Robotically assisted
      technology became available for use in 2000. Since that time, computer-enhanced
      technology for aortic anastomoses has been applied successfully in the animal
      model. Early application in the clinical setting for aortoiliac disease also has
      been successfully initiated. Robotic technology provides the vascular surgeon
      with the ability to perform the delicate tissue handling necessary for aortic
      procedures. Based on their knowledge of current procedures, surgeons must
      redesign their surgical strategies to adapt to this computer-enhanced
      methodology.

PMID- 15476654
TI  - Robotically assisted laparoscopic prostatectomy: an assessment of its
      contemporary role in the surgical management of localized prostate cancer.
AB  - Radical prostatectomy has maintained a cardinal role in the treatment of
      localized carcinoma of the prostate. The combination of refinements in surgical
      technique and better definition of the anatomy have decreased the morbidity from
      surgery. Nonetheless, concerns about treatment-related side effects remain the
      primary limitation of surgical therapy for prostate cancer. Laparoscopic
      prostatectomy, with or without robotic assistance, is playing an increasing role
      in surgical treatment of prostate cancer. However, the minimally invasive aspect
      of laparoscopy may have less relevance for radical prostatectomy because the open
      surgical procedure requires a limited infraumbilical incision. In the present
      series comparing robotically assisted laparoscopic prostatectomy with open
      radical retropubic prostatectomy, no difference was seen in postoperative pain,
      length of stay, or requirement for blood replacement. However, the most important
      outcome measures are tumor control, continence, and sexual potency. The
      outstanding visibility and precision afforded by the robotic approach may offer
      advantages in each of these areas.

PMID- 15476655
TI  - Robotics in neurosurgery.
AB  - Technological developments in imaging guidance, intraoperative imaging, and
      microscopy have pushed neurosurgeons to the limits of their dexterity and
      stamina. The introduction of robotically assisted surgery has provided surgeons
      with improved ergonomics and enhanced visualization, dexterity, and haptic
      capabilities. This article provides a historical perspective on neurosurgical
      robots, including image-guided stereotactic and microsurgery systems. The future
      of robot-assisted neurosurgery, including the use of surgical simulation tools
      and methods to evaluate surgeon performance, is discussed.

PMID- 15476656
TI  - Current status of robotically assisted coronary revascularization.
AB  - This article reviews the current status of totally endoscopic coronary
      revascularization using telemanipulation systems for robotic assistance. Current
      challenges in implementing a robotic surgical program are discussed, and
      application of the technology in both arrested and beating heart procedures is
      considered.

PMID- 15476657
TI  - Robotic mitral valve surgery.
AB  - Currently, cardiac surgery is an evolving field. Not only has there been a
      technological explosion, but there also is a strong interest in minimally
      invasive operations. Mitral valve surgery can now be performed with the use of
      sophisticated robotic systems through small incisions. The patient of today and
      the future will demand minimally invasive operations. Initial clinical experience
      with robotic systems will allow for further developments that, ultimately, may
      result in completely endoscopic heart surgery. In this rapidly evolving field, we
      review the recent history and clinical results of robotically assisted mitral
      valve surgery at our institution.

PMID- 15476658
TI  - Robotics in thoracic surgery.
AB  - Surgical use of robotics, or computer-assisted surgical systems (CAS), has
      evolved over the last 10 years; for the treatment of chest diseases, however, the
      development has really occurred in the last 3 to 4 years. This brief history
      means that there have been few publications in the medical literature, and those
      that exist are mostly case reports. Moreover, because of this modest experience,
      robotic thoracic procedures currently take more time than nonrobotic cases and,
      thus, are more expensive. The surgical learning curve appears to be steep,
      especially for the more complex procedures. As surgeons gain greater experience
      and the complexity and cost of the equipment are reduced, we should expect to see
      greater utility of CAS in thoracic surgery.

PMID- 15476659
TI  - Robotic pediatric cardiac surgery: present and future perspectives.
AB  - Advances in robotic technology and imaging systems have enabled the broad
      application of minimally invasive techniques in cardiac surgery, including
      coronary artery bypass grafting and mitral valve repair in adults. In pediatric
      cardiac surgery, however, current robotic systems have been used primarily to
      facilitate thoracoscopic pediatric procedures on extracardiac lesions, such as
      ligation of patent ductus and division of vascular rings. The use of smaller
      instruments with sophisticated robotic wrists may make it possible to perform
      more complex extracardiac procedures even in young infants. Additionally, future
      technological improvements, including incorporation of tactile feedback,
      instrument tracking, and intracardiac imaging (such as real-time 3-dimensional
      echocardiography), may enable intracardiac robotic surgery to be performed in
      children. This article reviews the current and potential future applications of
      pediatric robotic surgery and the developmental work required to enable
      performance of these procedures, along with an overview of the problems
      associated with the use of current robotic surgical systems in children.

PMID- 15476660
TI  - Robotic arrhythmia surgery and resynchronization.
AB  - Over the last decade, significant technological advancements have occurred in
      cardiac surgery. One such breakthrough has been the use of robotic
      telemanipulation systems, which allow the surgeon to perform cardiac surgery
      through a minimally invasive approach. As a result, surgery for atrial
      fibrillation and resynchronization therapy for congestive heart failure have been
      increasingly incorporated into the surgeon's armamentarium.

PMID- 15476661
TI  - Plasmodium berghei: dehydroepiandrosterone sulfate reverses chloroquino
      resistance in experimental malaria infection; correlation with glucose 6
      phosphate dehydrogenase and glutathione synthesis pathway.
AB  - In Plasmodium falciparum-infected cells or in P. berghei infected mice, increase
      of reduced glutathione (GSH) levels confers resistance to chloroquine (CQ). GSH
      is synthesized within the cells through a complex biochemical pathway composed of
      several well known enzymes, in which glucose-6-phosphate dehydrogenase (G6PD)
      plays an important role. The physiological hormone dehydroepiandrosterone sulfate
      (DHEAS) is a potent inhibitor of G6PD activity, and G6PD deficiency is known to
      exert antimalaria protection. This study aimed to investigate the ability of
      DHEAS to enhance the antimalarial activity of CQ, via an inhibition of G6PD
      activity and GSH synthesis. Two P. berghei CQ resistant strains (CQR6 and CQR30)
      were selected in vivo from the sensitive strain NK65. Drug effects were checked
      both by monitoring the evolution of parasitaemia and by the survival of infected
      mice. In addition, intra-parasite levels of GSH and G6PD activity were measured
      before and after the treatment. Results demonstrate that acquisition of CQ
      resistance in P. berghei is associated with a significant increase in parasite
      G6PD activity and GSH level. Combination of CQ with DHEAS or buthionin sulfoximin
      (BSO, a specific inhibitor of GSH synthesis) significantly increased sensitivity
      of resistant parasites to CQ and increased the survival period of the infected
      mice. This reduction of parasitaemia and improvement of the survival of infected
      mice were associated with intra-parasite depletion of GSH and inhibition of G6PD
      activity due to DHEAS action. This experimental study suggests that DHEAS could
      be used to potentiate antimalarial action of CQ, particularly on CQ resistant
      strains.

PMID- 15476662
TI  - Novel antitumor indenoindole derivatives targeting DNA and topoisomerase II.
AB  - We have identified a novel series of indenoindole derivatives endowed with potent
      cytotoxic activities toward cancer cells. Five compounds containing a 8-[2
      (dialkylamino)ethoxy]-2,3-dimethoxy-5H-10H-indeno[1,2-b]indol-10-one-O-propynyl
      oxime core substituted with a phenyl, furanyl, or a methyl substituent on the
      propynyl side chain have been synthesized and their mechanism of action was
      investigated using a panel of complementary biophysical and biochemical
      techniques. The compounds were shown to intercalate into DNA with a preference
      for AT-rich sequences. They have no effect on topoisomerase I but they strongly
      stimulate DNA cleavage by topoisomerase II. Their capacity to stabilize
      topoisomerase II-DNA covalent complexes is comparable to that of the reference
      drug etoposide. The nature and orientation of the substituent on the propynyl
      chain modulate the DNA binding and topoisomerase II inhibitory properties of the
      compounds and, apparently, there is a correlation between the cytotoxic potential
      and the molecular action at the DNA-topoisomerase II level. The growth of human
      K562 leukemia cells is strongly reduced in the presence of the indenoindoles
      (IC(50) in the 50nM range) which maintain a high cytotoxic activity toward the
      adriamycin-resistant K562adr cells line in vitro. The low resistance indexes
      measured with the indenoindoles (RRI = 10-30) compared to adriamycin (RRI = 1000)
      suggest that our new compounds are weakly or not sensitive to drug efflux
      mediated by glycoprotein-P and/or multidrug resistance (MDR) protein pumps.
      Finally, we also show that these indenoindoles arrest K562 cells in the G2/M
      phase of the cell cycle and promote apoptosis, as indicated by the appearance of
      internucleosomal DNA cleavage. One compound in the series was tested for in vivo
      antitumor activity against the colon 38 model and at 25mg/kg it showed 100%
      complete tumor regression in the treated mice, without significant body weight
      loss. Altogether, the results reported here establish that our indenoindole
      derivatives represent a novel interesting series of DNA-targeted cytotoxic
      agents.

PMID- 15476663
TI  - Specificity of action of bisindolylmaleimide protein kinase C inhibitors: do they
      inhibit the 70kDa ribosomal S6 kinase in cardiac myocytes?
AB  - Bisindolylmaleimide protein kinase C (PKC) inhibitors, such as GF109203X and Ro31
      8220, are used as pharmacological tools in many cellular systems. However, in
      vitro, GF109203X and Ro31-8220 also inhibit the 70kDa ribosomal S6 kinase
      (p70(S6K)) with similar potency. We determined whether GF109203X and Ro31-8220
      inhibit p70(S6K) activity in intact adult rat ventricular myocytes (ARVM). First,
      we confirmed that increased phosphorylation of the 40S ribosomal S6 protein (a
      cellular substrate for both p70(S6K) and the 90 kDa ribosomal S6 kinase) in
      response to stimulation of ARVM by insulin-like growth factor-1 (300 ng/mL; 10
      min) occurs specifically through rapamycin-sensitive activation of p70(S6K).
      Then, using this response as the index of cellular p70(S6K) activity, we
      determined the effects of GF109203X and Ro31-8220 (1, 3 or 10 microM) on such
      activity. At these concentrations, neither GF109203X nor Ro31-8220 inhibited
      cellular p70(S6K) activity. In contrast, even at 1 microM, cellular PKC activity
      (stimulated by a 3 min exposure to 30 nM phorbol 12-myristate 13-acetate) was
      significantly inhibited by each agent. We conclude that; (1) data obtained in
      vitro may not necessarily be extrapolated to intact cells and (2) inhibition of
      p70(S6K) is unlikely to contribute to the actions of GF109203X and Ro31-8220 in
      ARVM.

PMID- 15476664
TI  - Inhibitory mechanism of caffeine on insulin-stimulated glucose uptake in adipose
      cells.
AB  - Caffeine inhibits insulin-induced glucose uptake in rat adipocytes and also
      decreases insulin sensitivity, including whole-body glucose disposal and glucose
      uptake in skeletal muscle, during a euglycemic-hyperinsulinemic clamp in human.
      However, the mechanism by which caffeine decreases the insulin sensitivity is not
      still clear. We found that pre-treatment with caffeine inhibited the insulin
      induced 2-deoxy-D-[1-(3)H]glucose uptake in a concentration-dependent manner in
      mouse preadipose MC-3T3-G2/PA6 cells differentiated into mature adipose cells.
      Caffeine also suppressed insulin-induced GLUT4 translocation in the
      differentiated cells. Although caffeine did not alter insulin-induced activation
      of PI3K and protein kinase C-zeta (PKCzeta), an isoform of atypical PKC, which is
      reported to have an important role in insulin-induced GLUT4 translocation, we
      found that insulin-induced phosphorylation and activation of Akt were blocked by
      pre-treatment with caffeine. Inhibition of insulin-induced 2-deoxy-D-[1
      (3)H]glucose uptake by caffeine was also observed in primary cultured brown
      adipocytes in a concentration-dependent manner. These results may, in part,
      explain the ability of caffeine to decrease insulin sensitivity.

PMID- 15476665
TI  - Quercetin prevents oxidative stress and NF-kappaB activation in gastric mucosa of
      portal hypertensive rats.
AB  - The present study was designed to investigate the effects of quercetin on
      oxidative stress and activation of nuclear factor kappa B (NF-kappaB) in an
      experimental model of portal hypertensive gastropathy induced by partial portal
      vein ligation (PPVL). Portal pressure was significantly elevated in PPVL rats.
      Transaminase and alkaline phosphatase activities were not significantly modified,
      indicating absence of liver injury. Histological analysis of gastric sections
      showed a lost of normal architecture, with edema and vasodilatation. The
      cytosolic concentration of thiobarbituric acid reactive substances and the
      lipoperoxidation measurement by chemiluminiscence were significantly increased.
      Superoxide dismutase activity in gastric mucosa was significantly reduced. Portal
      hypertensive gastropathy induced a marked activation of NF-kappaB, accompanied by
      a decrease in IkappaB protein levels and a significant induction of nitric oxide
      synthase (iNOS) protein. Administration of quercetin markedly alleviated
      histological abnormalities and inhibited oxidative stress and NF-kappaB
      activation. IkappaB decrease and induction of iNOS protein were partially
      prevented by quercetin. Quercetin treatment, by abolishing the NF-kappaB signal
      transduction pathway, may block the production of noxious mediators involved in
      the pathogenesis of portal hypertensive gastropathy.

PMID- 15476666
TI  - Rabbit neutrophil chemotactic protein (NCP) activates both CXCR1 and CXCR2 and is
      the functional homologue for human CXCL6.
AB  - Neutrophil chemotactic protein (NCP) is a rabbit CXC chemokine with activating
      and chemotactic properties on neutrophilic granulocytes. Although its selective
      activity on neutrophils is demonstrated, its interactions with specific chemokine
      receptors are not defined. For further functional characterization, NCP was
      chemically synthesized and was found to be equipotent as natural NCP in
      neutrophil chemotaxis. To identify its human homologue, we separately expressed
      two potential rabbit NCP receptors (CXCR1 and CXCR2) in Jurkat cells. Pure
      synthetic NCP was equally efficient to promote chemotaxis through either rabbit
      CXCR1 or CXCR2. Moreover, chemotaxis assays on rabbit CXCR1 and CXCR2
      transfectants showed that NCP uses the same receptors as interleukin-8 (IL-8), a
      major rabbit CXC chemokine, but not rabbit GROalpha, which only recognized CXCR2.
      In addition, specific inhibitors for CXCR1 or CXCR2 reduced rabbit neutrophil
      chemotaxis induced by NCP and rabbit IL-8. Furthermore, NCP and the structurally
      related human CXCR1/CXCR2 agonist CXCL6/GCP-2 (granulocyte chemotactic protein-2)
      cross-desensitized each other in intracellular calcium release assays on human
      neutrophils, further indicating that both chemokines share the same receptors.
      The inflammatory role of NCP was also evidenced by its potent granulocytosis
      inducing capacity in rabbits upon systemic administration. This study provides in
      vitro and in vivo evidences that NCP is the functional rabbit homologue for human
      CXCL6/GCP-2 rather than the most related CXCR2 agonist CXCL5/ENA-78 (epithelial
      cell-derived neutrophil activating peptide-78). It is concluded that the rabbit
      is a better model to study human neutrophil activation compared to mice, which
      lack CXCL8/IL-8.

PMID- 15476667
TI  - Elucidation of the mechanism of inhibition of cyclooxygenases by acyl-coenzyme A
      and acylglucuronic conjugates of ketoprofen.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the cyclooxygenase (COX)
      isoforms which accounts for their clinical effects. The differential inhibition
      of COX-1 and COX-2 is not sufficient to explain the absence of a correlation
      between in vitro and in vivo effects, especially for 2-aryl-propionates, thus
      indicating the participation of metabolites. Conjugates to glucuronic acid and to
      coenzyme-A are mainly produced, and have been shown to be chemically reactive.
      Therefore, we studied the interaction of the ketoprofen metabolites with the COX
      enzymes. After incubation with bovine pulmonary artery endothelial cells (BPAEC),
      COX-1 was inhibited stereoselectively by S-ketoprofen acylglucuronide, and more
      significantly by CoA-thioester. After washing-out the medium, COX-1 activity was
      essentially recovered, indicating a reversible inhibition. In LPS-stimulated
      J774.2 cells, COX activity (mainly inducible COX-2) was inhibited reversibly and
      stereospecifically by S-ketoprofen glucuronide, whereas it disappeared totally
      and was not recovered after incubation with CoA-thioester. Correspondingly,
      inhibition of purified COX-2 with this compound was observed to be rapid and
      irreversible. Using an anti-ketoprofen antibody, COX immunoprecipitated from
      cells exhibited adduct formation for COX-2 but not for COX-1. This was observed
      after incubation with CoA-thioester, and, surprisingly, also with glucuronide.
      Molecular docking gave support to explain this discrepancy: the glucuronide was
      found to establish a strong interaction with Y115 located in the membrane binding
      domain, whereas the thioester was preferentially bound to the active site of the
      enzyme. Overall, our results suggest a contribution of CoA-thioester metabolites
      of carboxylic NSAIDs to their pharmacological action by irreversibly and
      selectively inhibiting COX-2.

PMID- 15476668
TI  - Photoreceptor preservation in the S334ter model of retinitis pigmentosa by a
      novel estradiol analog.
AB  - The cytoprotective activity of MITO-4565, a novel, non-hormonal, estradiol
      derivative, was evaluated in the S334ter transgenic model of retinitis pigmentosa
      (RP). Progressive blindness in RP is due to apoptotic death of the
      photoreceptors, a process mimicked by the animal models [Portera-Cailliau C, Sung
      C-H, Nathans J, Adler R. Apoptotic photoreceptor cell death in mouse models of
      retinitis pigmentosa. Proc Natl Acad Sci USA 1994;91:974-8]. On postnatal day 9,
      10 transgenic S334ter rats received a single intraocular injection of MITO-4565
      in the left eye, and vehicle in the right eye. By postnatal day 20, the thickness
      of the outer nuclear layer (ONL) in the superior retina of the untreated eyes was
      5.76 +/- 1.12 microm (N = 10), versus 10.72 +/- 1.52 microm (N = 10) for eyes
      treated with MITO-4565 (P < 0.0001, ANOVA F = 1671). Comparable cytoprotection
      was also observed for the inferior retina. Cytoprotection by MITO-4565 was also
      observed in primary cultures of rat retinal ganglion cells against NMDA
      excitotoxicity. Data from studies of hexose monophosphate shunt flux,
      mitochondrial stability, and in vitro lipid peroxidation, are in accord with
      previous reports [Green PS, Gridley KE, Simpkins JW. Nuclear estrogen receptor
      independent neuroprotection by estratrienes: a novel interaction with
      glutathione. Neuroscience 1997;84:7-10]; a likely mechanism of action entails
      moderation of membrane lipid peroxidation in a redox couple with glutathione.
      Such preservation of membrane integrity is particularly crucial to mitochondria,
      where collapse of membrane potential precipitates cell death, and where GSH is
      maintained at mM concentrations. Indeed, exposure to MITO-4565, but not a methoxy
      substituted negative control, allowed mitochondria to retain membrane potential
      (DeltaPsi(m)) under conditions of Ca(2+) overload that would normally induce
      complete mitochondrial failure. Mitochondrial interventions offer a novel
      therapeutic approach for RP, and other degenerative diseases of the retina.

PMID- 15476669
TI  - 2-Substituted adenosine derivatives: affinity and efficacy at four subtypes of
      human adenosine receptors.
AB  - The affinity and efficacy at four subtypes (A(1), A(2A), A(2B) and A(3)) of human
      adenosine receptors (ARs) of a wide range of 2-substituted adenosine derivatives
      were evaluated using radioligand binding assays and a cyclic AMP functional assay
      in intact CHO cells stably expressing these receptors. Similar to previous
      studies of the N(6)-position, several 2-substituents were found to be critical
      structural determinants for the A(3)AR activation. The following adenosine 2
      ethers were moderately potent partial agonists (K(i), nM): benzyl (117), 3
      chlorobenzyl (72), 2-(3-chlorophenyl)ethyl (41), and 2-(2-naphthyl)ethyl (130).
      The following adenosine 2-ethers were A(3)AR antagonists: 2,2-diphenylethyl, 2-(2
      norbornan)ethyl, R- and S-2-phenylbutyl, and 2-(2-chlorophenyl)ethyl. 2-(S-2
      Phenylbutyloxy)adenosine as an A(3)AR antagonist right-shifted the concentration
      response curve for the inhibition by NECA of cyclic AMP accumulation with a K(B)
      value of 212 nM, which is similar to its binding affinity (K(i) = 175 nM). These
      2-substituted adenosine derivatives were generally less potent at the A(1)AR in
      comparison to the A(3)AR, but fully efficacious, with binding K(i) values over
      100 nM. The 2-phenylethyl moiety resulted in higher A(3)AR affinity (K(i) in nM)
      when linked to the 2-position of adenosine through an ether group (54), than when
      linked through an amine (310) or thioether (1960). 2-[2-(l
      Naphthyl)ethyloxy]adenosine (K(i) = 3.8 nM) was found to be the most potent and
      selective (>50-fold) A(2A) agonist in this series. Mixed A(2A)/A(3)AR agonists
      have been identified. Interestingly, although most of these compounds were
      extremely weak at the A(2B)AR, 2-[2-(2-naphthyl)ethyloxy]adenosine (EC(50) = 1.4
      microM) and 2-[2-(2-thienyl)-ethyloxy]adenosine (EC(50) = 1.8 microM) were found
      to be relatively potent A(2B) agonists, although less potent than NECA (EC(50) =
      140 nM).

PMID- 15476670
TI  - Antiaggregatory activity in human platelets of potent antagonists of the P2Y 1
      receptor.
AB  - Activation of the P2Y(1) nucleotide receptor in platelets by ADP causes changes
      in shape and aggregation, mediated by activation of phospholipase C (PLC).
      Recently, MRS2500(2-iodo-N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'
      bisphosphate) was introduced as a highly potent and selective antagonist for this
      receptor. We have studied the actions of MRS2500 in human platelets and compared
      these effects with the effects of two acyclic nucleotide analogues, a
      bisphosphate MRS2298 and a bisphosphonate derivative MRS2496, which act as P2Y(1)
      receptor antagonists, although less potently than MRS2500. Improved synthetic
      methods for MRS2500 and MRS2496 were devised. The bisphosphonate is predicted to
      be more stable in general in biological systems than phosphate antagonists due to
      the non-hydrolyzable CP bond. MRS2500 inhibited the ADP-induced aggregation of
      human platelets with an IC(50) value of 0.95 nM. MRS2298 and MRS2496 also both
      inhibited the ADP-induced aggregation of human platelets with IC(50) values of
      62.8 nM and 1.5 microM, respectively. A similar order of potency was observed for
      the three antagonists in binding to the recombinant human P2Y(1) receptor and in
      inhibition of ADP-induced shape change and ADP-induced rise in intracellular
      Ca(2+). No substantial antagonism of the pathway linked to the inhibition of
      cyclic AMP was observed for the nucleotide derivatives, indicating no interaction
      of these three P2Y(1) receptor antagonists with the proaggregatory P2Y(12)
      receptor, which is also activated by ADP. Thus, all three of the bisphosphate
      derivatives are highly selective antagonists of the platelet P2Y(1) receptor, and
      MRS2500 is the most potent such antagonist yet reported.

PMID- 15476671
TI  - Antioxidant effect of hydroxytyrosol, a polyphenol from olive oil: scavenging of
      hydrogen peroxide but not superoxide anion produced by human neutrophils.
AB  - Hydroxytyrosol (HT) (also known as dihydroxyphenylethanol (DPE)) is a polyphenol
      extracted from virgin olive oil. HT is known to exert an antioxidant effect but
      the mechanism of action and the identity of the reactive oxygen molecule(s)
      targeted are not known. In this study, we show that HT inhibits luminol-amplified
      chemiluminescence of human neutrophils stimulated with N-formyl-methionyl-leucyl
      phenylalanine (fMLP), phorbol myristate acetate (PMA) and opsonized zymosan. This
      effect was dose-dependent and occurred immediately after the addition of HT.
      However, HT had no effect on lucigenin-amplified chemiluminescence, suggesting
      that it does not inhibit NADPH oxidase activation or scavenge superoxide anions.
      Furthermore, HT inhibited H(2)O(2)-dependent-dichlorofuoroscein (DCFH)
      fluorescence of activated neutrophils, as measured by flow cytometry. Finally, HT
      inhibited luminol-amplified chemiluminescence in a cell-free system consisting of
      H(2)O(2) and HRPO. These results suggest that HT, a polyphenol derived from olive
      oil, could exert its antioxidant effect by scavenging hydrogen peroxide but not
      superoxide anion released during the respiratory burst.

PMID- 15476672
TI  - Inhibition of insulin-like growth factor I receptor tyrosine kinase by ethanol.
AB  - Ethanol inhibits insulin and insulin-like growth factor-I (IGF-I) signaling in a
      variety of cell types leading to reduced mitogenesis and impaired survival. This
      effect is associated with inhibition of insulin receptor (IR) and insulin-like
      growth factor-I receptor (IGF-IR) autophosphorylation, which implicates these
      receptors as direct targets for ethanol. It was demonstrated previously that
      ethanol inhibits the autophosphorylation and kinase activity of the purified
      cytoplasmic tyrosine kinase domain of the IR. We performed computer modeling of
      the ethanol interaction with the IR and IGF-IR kinases (IRK and IGF-IRK). The
      analysis predicted binding of alcohols within the hydrophobic pocket of the
      kinase activation cleft, with stabilization at specific polar residues. Using IGF
      IRK purified from baculovirus-infected insect cells, ethanol inhibited peptide
      substrate phosphorylation by non-phosphorylated IGF-IRK, but had no effect on the
      autophosphorylated enzyme. In common with the IRK, ethanol inhibited IGF-IRK
      autophosphorylation. In cerebellar granule neurons, ethanol inhibited
      autophosphorylation of the apo-IGF-IR, but did not reverse IGF-IR phosphorylation
      after IGF-I stimulation. In summary, the findings demonstrate direct inhibition
      of IGF-IR tyrosine kinase by ethanol. The data are consistent with a model
      wherein ethanol prevents the initial phase of IRK and IGF-IRK activation, by
      inhibiting the engagement of the kinase activation loop.

PMID- 15476673
TI  - Differential sensitivity to resveratrol-induced apoptosis of human chronic
      myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells.
AB  - The in vitro effects of resveratrol (RES) on apoptotic pathway in human chronic
      myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells were investigated.
      RES treatment of both cell types significantly and irreversibly inhibited their
      growth, associated with extensive apoptosis and increase in hypodiploid cells.
      Cell cycle analysis showed accumulation in G(1) phase in HSB-2 drug exposed
      cells, while only K562-treated cells exhibited a marked accumulation in S phase
      with a concomitant decrease in G(1) and G(2)/M at 24 h. Moreover, RES caused
      internucleosomal DNA fragmentation, even if K562 cells were found less sensitive
      to the drug, as compared to HSB-2 cells, which also reacted earlier to the
      treatment. RES-induced apoptosis was associated with an increase of Bax
      expression and a marked release of cytochrome c from mitochondria. Interestingly,
      K562 cells exhibited a basal content of glutathione 10-fold that of HSB-2 cells,
      which increased after 24-48 h RES exposure, together with increment of
      glutathione reductase and peroxidase activities. However, the major resistance to
      apoptosis of K562 cells cannot be attributed to their higher pool of reducing
      power, since neither the inhibition of glutathione synthesis by buthionine
      sulphoximine nor glutathione depletion by diethylmaleate, sensitized these cells.
      In addition, glutathione enrichment of HSB-2 cells by N-acetylcysteine did not
      prevent the apoptotic effects of RES. Our data indicate that RES commitment to
      apoptosis in both cell lines is independent from the intracellular content of
      glutathione, while it is associated with either the enhanced expression of Bax
      and cytochrome c release.

PMID- 15476674
TI  - A novel cancer therapy: combined liposomal hypoxia inducible factor 1 alpha
      antisense oligonucleotides and an anticancer drug.
AB  - The combined influence of doxorubicin (DOX) and liposomal antisense
      oligonucleotides (ASOs) targeted to hypoxia-inducible factor 1 alpha (HIF1A)
      subunit on the apoptosis signaling pathways and cellular pump and nonpump
      resistance were investigated. Drug-sensitive A2780 and multidrug-resistant
      A2780/AD human ovarian carcinoma cells were used. Cells were incubated within 48h
      in normoxic (21% O(2), 5% CO(2) and 74% N(2)) or hypoxic (1% O(2), 5% CO(2) and
      94% N(2)) conditions, with or without DOX in the concentration corresponding to
      the IC(50) dose, with or without liposomal ASO targeted to HIF1A mRNA. Apoptosis
      induction, lactic acid concentration, expression of genes and proteins involved
      in apoptosis signaling pathways, pump and nonpump cellular resistance were
      assessed. The results showed that overexpression of HIF1A protein induced by
      exposure to hypoxia and DOX activated both apoptotic cellular signal and cellular
      antiapoptotic defense. In addition, while hypoxia suppressed cellular pump
      resistance, due to multidrug resistance-associated protein family transporters,
      DOX activated pump resistance. A decrease in the expression of targeted protein
      (HIF1A) by liposomal HIF1A ASO effectively suppressed pump and nonpump cellular
      resistance and significantly enhanced apoptosis induction by hypoxia and DOX.
      Data obtained showed that ASO targeted to HIF1A mRNA that suppress cellular
      antihypoxic defense might be used as a powerful tool to improve the anticancer
      action of cytotoxic drug or even as an anticancer agent.

PMID- 15476675
TI  - Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) by curcumin
      I, II, and III purified from Turmeric powder.
AB  - P-glycoprotein (Pgp, ABCB1) is an ATP-dependent drug efflux pump linked to
      development of multidrug resistance (MDR) in cancer cells. Previously [Biochem
      Pharmacol 2002;64:573-82], we reported that a curcumin mixture could modulate
      both function and expression of Pgp. This study focuses on the effect of three
      major curcuminoids--curcumin I, II and III purified from a curcumin mixture--on
      modulation of Pgp function in a multidrug resistant human cervical carcinoma cell
      line (KB-V1). The similar IC(50) values for cytotoxicity of curcuminoids of KB
      V1, and KB-3-1 (parental drug sensitive cell line) suggest that these
      curcuminoids may not be substrates for Pgp. Treating the cells with non-toxic
      doses of curcuminoids increased their sensitivity to vinblastine only in the Pgp
      expressing drug resistant cell line, KB-V1, and curcumin I retained the drug in
      KB-V1 cells more effectively than curcumin II and III, respectively. Effects of
      each curcuminoid on rhodamine123, calcein-AM, and bodipy-FL-vinblastine
      accumulation confirmed these findings. Curcumin I, II and III increased the
      accumulation of fluorescent substrates in a dose-dependent manner, and at 15
      microM, curcumin I was the most effective. The inhibitory effect in a
      concentration-dependent manner of curcuminoids on verapamil-stimulated ATPase
      activity and photoaffinity labeling of Pgp with the [(125)I]
      iodoarylazidoprazosin offered additional support; curcumin I was the most potent
      modulator. Taken together, these results indicate that curcumin I is the most
      effective MDR modulator among curcuminoids, and may be used in combination with
      conventional chemotherapeutic drugs to reverse MDR in cancer cells.

PMID- 15476676
TI  - The blockade of cyclopiazonic acid-induced store-operated Ca2+ entry pathway by
      YC-1 in neutrophils.
AB  - In the presence of external Ca2+, pretreatment of neutrophils with 3-(5'
      hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) inhibited the cyclopiazonic acid
      (CPA)-induced [Ca2+](i) elevation in a concentration- but not a time-dependent
      manner, while YC-1 had no effect on the Ca2+ signals in a Ca2+-free medium. YC-1
      failed to inhibit ATP- and interleukin-8 (IL-8)-induced [Ca2+](i) changes.
      Addition of YC-1 after cell activation strongly inhibited the CPA-induced
      [Ca2+](i) changes. In a classical Ca2+ readdition protocol, a similar extent
      inhibition of Ca2+ spike by YC-1 introduced either prior to or after CPA
      stimulation was obtained. In rat neutrophils, mRNA for endothelial
      differentiation gene (edg)1, edg5, edg6 and edg8, the putative targets for
      sphingosine 1-phosphate (S1P), could be detected. However, S1P was found to have
      little effect on Ca(2+) signals. YC-1 did not inhibit but enhanced the
      sphingosine-induced [Ca2+](i) changes. Inhibition by YC-1 of CPA-induced
      [Ca2+](i) changes was not prevented by 7-nitroindazole and N-(3
      aminomethyl)benzylacetamidine (1400W), two nitric oxide synthase (NOS)
      inhibitors, by aristolochic acid, a phospholipase A(2) inhibitor, or by
      suspension in a Na(+)-deprived medium. YC-1 did not affect the mitochondrial
      membrane potential. Moreover, YC-1 did not alter [Ca2+](i) changes in response to
      ionomycin after CPA and formyl-Met-Leu-Phe (fMLP) stimulation in a Ca2+-free
      medium. YC-1 had no effect on the basal [Ca2+](i) level, the pharmacologically
      isolated plasma membrane Ca2+-ATPase activity, and Ba2+ entry into CPA-activated
      cells. YC-1 alone resulted in the accumulation of actin filaments in neutrophils,
      while significantly reduced the intensity of actin filament staining in the
      subsequent activation with CPA. These results indicate that YC-1 inhibited CPA
      activated store-operated Ca2+ entry (SOCE) probably through the direct blockade
      of channel activation and/or the disruption of the integrity of the actin
      cytoskeleton necessary for supporting Ca2+ entry pathway in neutrophils.

PMID- 15476677
TI  - Role of the permeability transition pore in cytochrome C release from
      mitochondria during ischemia-reperfusion in rat liver.
AB  - Ischemia and reperfusion cause mitochondrial dysfunctions that initiate the
      mitochondrial apoptosis pathway. They involve the release of cytochrome C and the
      activation of the caspase cascade but the mechanism(s) leading to cytochrome C
      release is(are) poorly understood. The aim of this study was to analyse the
      relation between cytochrome C release and the opening of the permeability
      transition pore (PTP) during in situ liver ischemia and reperfusion. Liver
      ischemia was induced for 30, 60 and 120 min and blood re-flow was subsequently
      restored for 30 and 180 min. Ischemia hugely altered mitochondrial functions,
      i.e., oxidative phosphorylation and membrane potential, and was accompanied by a
      time-dependent mitochondrial release of cytochrome C into the cytosol and by
      activations of caspases-3 and -9. PTP opening was not observed during ischemia,
      as demonstrated by the absence of effect of an in vivo pre-treatment of rats with
      cyclosporin A (CsA), a potent PTP inhibitor. Cytochrome C release was due neither
      to a direct effect of caspases onto mitochondria nor to an interaction of Bax or
      Bid with the mitochondrial membrane but could be related to a direct effect of
      oxygen deprivation. In contrast, during reperfusion, CsA pre-treatment inhibits
      cytochrome C release, PTP opening and caspase activation. At this step,
      cytochrome C release is likely to occur as a consequence of PTP opening. In
      conclusion, our study reveals that cytochrome C release, and thus the induction
      of the mitochondrial cell death pathway, occur successively independently and
      dependent on PTP opening during liver ischemia and reperfusion, respectively.

PMID- 15476678
TI  - Shift in purine/pyrimidine base recognition upon exchanging extracellular domains
      in P2Y 1/6 chimeric receptors.
AB  - P2Y receptors are G protein-coupled receptors stimulated by extracellular
      nucleotides. Both the P2Y(1) and the P2Y(6) receptors are preferentially
      activated by nucleoside 5'-diphosphates, but favor different base moieties. In
      the case of the P2Y(1) receptor the preferred base is adenine, while the P2Y(6)
      receptor is activated by uracil nucleotides. To identify potential amino acid
      domains that interact with the base moiety, we used a chimeric receptor approach,
      employing the human P2Y(1) receptor as core structure to investigate the role in
      receptor activation of extracellular loops (ELs) and transmembrane domains (TMs)
      of the rat P2Y(6) receptor. The chimeric receptors were expressed in COS-7 cells
      and measured for stimulation of phospholipase C (PLC) induced by the potent
      P2Y(1) receptor agonist 2-MeSADP or the potent P2Y(6) receptor agonist UDP.
      Replacement of the N-terminus or EL2 resulted in low ( approximately 50 microM)
      potency of the agonist 2-MeSADP, thus confirming the importance of EL2 in ligand
      recognition. Upon replacement of several regions, the potency of the P2Y(1)
      agonist 2-MeSADP was either 1-2 microM (N-terminus and EL1, or EL1 and EL3) or 72
      microM (N-terminus and EL3). Concurrent replacement of three regions (N-terminus,
      EL1, and EL3) completely precluded activation by 2-MeSADP. Our study identified
      domains of the P2Y(6) receptor that contribute to receptor activation by UDP and
      hence seem to be involved in uracil recognition. Upon replacement with
      extracellular domains of the P2Y(6) receptor sequence we observed a trend toward
      gain of receptor-induced PLC activation by UDP, for example, in the chimera
      containing replacements of both the N-terminus and EL1. Exchange of three
      receptor domains led to a construct with an EC(50) value for UDP of 19 microM and
      a maximal inositol phosphate accumulation similar to the native P2Y(6) receptor.
      Within receptor constructs of combined domain exchanges the additional
      substitution of Tyr(110) by the corresponding Asn from the P2Y(6) receptor showed
      a significant increase for activation by UDP, but only when combined with the N
      terminal domain and TM1. The residue Tyr(110) was identified to play an important
      role in the recognition of the nucleobase in the P2Y(1) and P2Y(6) receptors.

PMID- 15476679
TI  - Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig
      and their structure-activity relationships.
AB  - The structure-activity relationships of flavonoids with regard to their
      inhibitory effects on phosphodiesterase (PDE) isozymes are little known. The
      activities of PDE1-5 were measured by a two-step procedure using cAMP with [(3)H]
      cAMP or cGMP with [(3)H]-cGMP as substrates. In the present results, PDE1, 5, 2,
      and 4 isozymes were partially purified from guinea pig lungs in that order, and
      PDE3 was from the heart. The IC(50) values of PDE1-5 were greater than those
      reported previously for the reference drugs, vinpocetin, EHNA, milrinone, Ro 20
      1724, and zaprinast, by 5-, 5-, 7-, 5-, and 3-fold, respectively. As shown in
      Table 2, luteolin revealed non-selective inhibition of PDE1-5 with IC(50) values
      in a range of 10-20 microM, as did genistein except with a low potency on PDE5.
      Daidzein, an inactive analogue of genistein in tyrosine kinase inhibition, showed
      selective inhibition of PDE3 with an IC(50) value of around 30 microM, as did
      eriodictyol with an IC(50) value of around 50 microM. Hesperetin and prunetin
      exhibited more-selective inhibition of PDE4 with IC(50) values of around 30 and
      60 microM, respectively. Luteolin-7-glucoside exhibited dual inhibition of
      PDE2/PDE4 with an IC(50) value of around 40 microM. Diosmetin more-selectively
      inhibited PDE2 (IC(50) of 4.8 microM) than PDE1, PDE4, or PDE5. However,
      biochanin A more-selectively inhibited PDE4 (IC(50) of 8.5 microM) than PDE1 or
      PDE2. Apigenin inhibited PDE1-3 with IC(50) values of around 10-25 microM.
      Myricetin inhibited PDE1-4 with IC(50) values of around 10-40 microM. The same
      was true for quercetin, but we rather consider that it more-selectively inhibited
      PDE3 and PDE4 (IC(50) of < 10 microM). In conclusion, it is possible to
      synthesize useful drugs through elucidating the structure-activity relationships
      of flavonoids with respect to inhibition of PDE isozymes at concentrations used
      in this in vitro study.

PMID- 15476681
TI  - Ensuring public trust.

PMID- 15476682
TI  - Neuroplasticity and schizophrenia.
AB  - This article's title is also the name of a workshop sponsored by the
      International Congress on Schizophrenia Research that was focused on an appraisal
      of the potential role of neuroplastic processes in the etiology or course of
      schizophrenia. The workshop brought together clinical investigators of
      schizophrenia and basic scientists who study various aspects of neuroplasticity,
      including central nervous system (CNS) development, learning and memory, and drug
      action. The goal was to identify special opportunities to advance knowledge and
      understanding of schizophrenia pathology, treatment, or prevention by applying
      neuroplasticity concepts as a framework to theories of the illness. Although the
      focus of this workshop was schizophrenia, the phenomena considered are pertinent
      to other disorders, such as depression and drug abuse.

PMID- 15476683
TI  - Voxel-based morphometry of patients with schizophrenia or bipolar disorder and
      their unaffected relatives.
AB  - BACKGROUND: Structural brain abnormalities in schizophrenia are well replicated;
      many emerge before the onset of illness and are present in relatives who remain
      well. Structural changes in bipolar disorder are less clearly established. The
      possibility that structural abnormalities might provide a means by which the
      disorders might be separated is one that has attracted limited research effort.
      This study sought to examine these issues and clarify the associations of
      phenotypic expression and genetic liability. METHODS: Forty-nine control
      subjects, 71 patients, and 72 unaffected relatives were recruited for the study.
      Patients included those with schizophrenia from families affected by
      schizophrenia alone, those with bipolar disorder from families affected by
      bipolar disorder alone, and those with bipolar disorder from families affected by
      both bipolar disorder and schizophrenia. Unaffected relatives were recruited from
      the families of the three patient groups. Subjects underwent a magnetic resonance
      imaging scan of the brain, which was analyzed with a grey-matter-optimized, voxel
      based morphometry technique. RESULTS: Compared with control subjects, all patient
      and relative groups showed evidence of reduced anterior thalamic gray matter.
      Reductions in middle prefrontal gyrus and dorsomedial thalamus were specific to
      participants with schizophrenia. CONCLUSIONS: Whereas prefrontal and dorsomedial
      thalamic gray matter reductions seem to be specific to schizophrenia, anterior
      thalamic reductions seem to be a marker of liability to psychosis in general.
      These results are discussed in the context of their functional role and in terms
      of their connections with other cortical and subcortical structures.

PMID- 15476684
TI  - The relationship between antisaccades, smooth pursuit, and executive dysfunction
      in first-episode schizophrenia.
AB  - BACKGROUND: Both oculomotor and neuropsychologic deficits have been used to
      support the hypothesis that schizophrenia is associated with prefrontal cortex
      dysfunction, but studies that have specifically investigated the relationships
      between these deficits have produced inconsistent findings. METHODS: We measured
      both smooth pursuit and antisaccade performance in a large group (n = 109) of
      patients with first-episode schizophrenia and a group of matched control subjects
      (n = 59) and investigated the relationship between performance on these tasks and
      performance on a range of executive tasks. We additionally explored the
      relationship between these variables and measures of psychopathology at
      presentation and duration of untreated psychosis. RESULTS: Antisaccade errors
      were significantly correlated with spatial working memory performance. Smooth
      pursuit gain did not correlate with any neuropsychologic measure. There were no
      reliable correlations between either oculomotor variables and measures of
      psychopathology and duration of untreated psychosis. CONCLUSIONS: These findings
      suggest that in schizophrenia working memory and antisaccade performance reflect
      the same abnormal prefrontal substrates and that smooth pursuit is mediated by a
      separate neural abnormality.

PMID- 15476685
TI  - Neurocognitive function in clinically stable men with bipolar I disorder or
      schizophrenia and normal control subjects.
AB  - BACKGROUND: Patients with bipolar disorder and schizophrenia have been shown to
      have neurocognitive deficits when compared with control subjects. The degree and
      pattern of impairment between psychiatric groups have rarely been compared,
      especially when subjects are psychiatrically stable. METHODS: Using a standard
      neurocognitive battery, we compared euthymic outpatients with bipolar disorder (n
      = 40), stable patients with schizophrenia (n = 20), and subjects with no
      psychiatric disorder (n = 22). The neurocognitive domains assessed included
      executive functioning, verbal memory, visual memory, procedural learning,
      visuoconstructive ability, and language functions. Effect sizes were calculated
      for each cognitive domain across groups. RESULTS: Stable schizophrenic subjects
      demonstrated a generalized cognitive impairment across most domains compared with
      control subjects, with average effect sizes of .9. Euthymic bipolar subjects were
      significantly impaired compared with control subjects only in executive
      functioning (Wisconsin Card Sorting Task) and verbal memory (California Verbal
      Learning Test) domains (effect sizes in the .8-.9 range). Performance on the
      executive function measures was bimodal among bipolar subjects, suggesting two
      subgroups: one with relatively normal and one with impaired executive
      functioning. No significant differences between the bipolar patient group and
      control subjects were observed in visuoconstructive ability, procedural learning,
      or language function. CONCLUSIONS: Both euthymic bipolar subjects and relatively
      stable schizophrenic subjects differed from control subjects in neurocognitive
      function. Among schizophrenic subjects, a generalized cognitive impairment was
      observed, and the degree of impairment was greater in the schizophrenic compared
      with the bipolar subjects. Subjects with bipolar disorder were impaired in two
      specific domains (verbal memory and executive function). Furthermore, within the
      bipolar group there was a subset with relatively normal executive functioning and
      a subset with significant impairment. Possible reasons for the persistence of
      these neurocognitive deficits in some subjects with bipolar disorder during
      periods of euthymia are reviewed.

PMID- 15476686
TI  - Chronic olanzapine or fluoxetine administration increases cell proliferation in
      hippocampus and prefrontal cortex of adult rat.
AB  - BACKGROUND: There has been increasing evidence that atypical antipsychotics are
      effective in the treatment of mood disorders or for augmenting 5
      hydroxytryptamine selective reuptake inhibitors for treatment-resistant
      depression. METHODS: Upregulation of neurogenesis in the adult hippocampus is a
      marker of antidepressant activity, and the present study investigated the
      influence of the atypical antipsychotic drug olanzapine on cell proliferation in
      the hippocampus of adult rat. The regulation of cell proliferation in the
      prelimbic cortex of adult rat was also examined. RESULTS: Chronic (21 days)
      olanzapine administration increased the number of newborn cells in the dentate
      gyrus of the hippocampus to the same extent as fluoxetine. Olanzapine or
      fluoxetine treatment also increased the number of proliferating cells in the
      prelimbic cortex. In contrast, there was no effect of either drug in the
      subventricular zone or primary motor cortex, and there was a trend for an
      increase in the striatum. Subchronic (7 days) administration of olanzapine had no
      effect on cell proliferation in hippocampus or prelimbic cortex, consistent with
      the time course for the effect of fluoxetine and the therapeutic actions of
      antidepressant treatment. The combination of olanzapine plus fluoxetine did not
      result in a greater induction of cell proliferation in either brain region.
      Analysis of the cell phenotype demonstrated that approximately 20% of the newborn
      cells in the prelimbic cortex differentiated into endothelial cells but not
      neurons, in contrast to the dentate gyrus, where most newborn cells
      differentiated into neurons. CONCLUSIONS: The results demonstrate that
      antidepressant or atypical antipsychotic medications can increase the
      proliferation of glia in limbic brain structures, an effect that could reverse
      the loss of glia that has been observed in depressed patients.

PMID- 15476687
TI  - Single nucleotide polymorphism and haplotype analysis of a novel tryptophan
      hydroxylase isoform (TPH2) gene in suicide victims.
AB  - BACKGROUND: Tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis
      of serotonin, represents a major candidate in numerous genetic association
      analyses of suicidal behavior; however, the results are so far inconclusive.
      Recently, a second tryptophan hydroxylase isoform (TPH2) was identified in mice,
      which was exclusively present in the brain. In a previous postmortem study of our
      own group, we could demonstrate that TPH2 is also expressed in the human brain
      but not in peripheral tissues. METHODS: We performed single nucleotide
      polymorphisms, haplotypes, and linkage disequilibrium studies on 263 suicide
      victims and 266 healthy control subjects with 10 single nucleotide polymorphisms
      in the TPH2 gene. RESULTS: Significant association was detected between one
      single nucleotide polymorphism (p = .004, global p = .01) and suicide.
      Additionally, haplotype analysis also produced support for association (p <
      .0001, global p = .0001). CONCLUSIONS: This is the first report about an
      association between TPH2 gene polymorphisms and completed suicide. Our findings
      provide evidence for an involvement of genetic variants in the TPH2 gene in
      suicidal behavior. These results might open up new research strategies for the
      analysis of the observed disturbances in the serotonergic system in several other
      psychiatric disorders.

PMID- 15476688
TI  - Tryptophan depletion and serotonin loss in selective serotonin reuptake inhibitor
      treated depression: an [(18)F] MPPF positron emission tomography study.
AB  - BACKGROUND: Recurrence of depressive symptoms after tryptophan depletion (TD) in
      selective serotonin reuptake inhibitor (SSRI)-treated depression is an important,
      unexplained phenomenon. With [(18)F] MPPF positron emission tomography (PET),
      serotonin (5-hydroxytryptamine, 5-HT) 1A receptor binding potential (5-HT(1A)BP)
      was measured after TD in various brain regions in citalopram-treated depression.
      This 5-HT(1A)BP measurement is sensitive to changes in extracellular 5-HT in
      animal models. METHODS: Eight remitted patients with major depressive disorder
      received [(18)F] MPPF PET scans twice: once after TD and once after sham
      depletion. Behavioral measures were evaluated with the Hamilton Depression Rating
      Scale and visual analog scales. RESULTS: No effect on regional 5-HT(1A)BP was
      observed after TD, despite an 86% decrease in total plasma tryptophan and
      transient depressive relapse in six of eight patients. CONCLUSIONS: Large
      magnitude changes in extracellular 5-HT are not crucial for the mood effects
      observed in SSRI-treated subjects after TD. Therefore, greater consideration must
      be given to other mechanisms that involve vulnerability to small perturbations in
      extracellular 5-HT, such as impairment of signal transduction.

PMID- 15476689
TI  - Prevention of postpartum episodes in women with bipolar disorder.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of divalproex
      (VLP) to prevent episode recurrence in postpartum women with bipolar disorder.
      METHODS: The design was a single-blind, nonrandomized clinical trial. Subjects
      were enrolled during pregnancy and chose either VLP plus symptom monitoring or
      monitoring without medication for immediate postpartum management. Mania and
      depression symptoms were assessed weekly for 20 weeks by an independent
      evaluator. RESULTS: Data were available for 26 women. There were no significant
      differences between groups in the proportions of women who developed postpartum
      hypomania/mania, depression, or mixed states. The time to development of episodes
      also did not vary between groups. Women who were treated with VLP tended to have
      lower levels of hypomanic/manic symptoms. CONCLUSIONS: Divalproex was not
      significantly more effective than monitoring without drug for the prevention of
      postpartum episodes of bipolar disorder. The most prudent pharmacologic plan is
      to use the drug(s) to which the individual woman has responded and prepare a plan
      for rapid augmentation if a breakthrough episode occurs.

PMID- 15476690
TI  - Effect of methylphenidate on executive functioning in adults with attention
      deficit/hyperactivity disorder: normalization of behavior but not related brain
      activity.
AB  - BACKGROUND: We examined the effect of prolonged methylphenidate (MPH) treatment
      on the functional neuroanatomy of executive functioning in adult men with
      attention-deficit/hyperactivity disorder (ADHD). METHODS: Positron emission
      tomography with [(15)O] water measured alterations of regional cerebral blood
      flow (rCBF) during the Paced Auditory Serial Addition Task and a control task in
      10 ADHD and 11 normal control men. Attention-deficit/hyperactivity disorder men
      were imaged unmedicated and after a clinically optimal dose of MPH for 3 weeks.
      RESULTS: Methylphenidate improved ADHD task performance, reduced rCBF in the
      prefrontal cortex (PFC), and increased rCBF in the right thalamus and precentral
      gyrus. Comparisons between the ADHD and normal control groups showed that normal
      control participants exhibited greater anterior cingulate cortex and temporal
      gyrus rCBF than ADHD participants under both conditions. Executive functioning
      was associated with greater subcortical (basal ganglia and cerebellar vermis)
      activation in the ADHD than normal control group under both conditions.
      CONCLUSIONS: Methylphenidate does not normalize task-related activity in ADHD.
      Task-related rCBF decreases in the PFC may be due to improved filtering out of
      task-irrelevant stimuli by way of MPH-mediated dopamine release in the PFC.

PMID- 15476691
TI  - Experience-dependent plasticity for attention to threat: Behavioral and
      neurophysiological evidence in humans.
AB  - Biased attention to threat represents a key feature of anxiety disorders. This
      bias is altered by therapeutic or stressful experiences, suggesting that the bias
      is plastic. Charting on-line behavioral and neurophysiological changes in
      attention bias may generate insights on the nature of such plasticity. We used an
      attention-orientation task with threat cues to examine how healthy individuals
      alter their response over time to such cues. In Experiments 1 through 3, we
      established that healthy individuals demonstrate an increased attention bias away
      from threat over time. For Experiment 3, we used functional magnetic resonance
      imaging to determine the neural bases for this phenomenon. Gradually increasing
      attention bias away from threat is associated with increased activation in the
      occipitotemporal cortex. Examination of plasticity of attention bias with
      individuals at risk for anxiety disorders may reveal how threatening stimuli come
      to be categorized differently in this population over time.

PMID- 15476692
TI  - Measurement of presynaptic zinc changes in hippocampal mossy fibers.
AB  - The hippocampal mossy fiber terminals of CA3 area contain high levels of
      vesicular zinc that is released in a calcium-dependent way, following high
      frequency stimulation. However the properties of zinc release during normal
      synaptic transmission, paired-pulse facilitation and mossy fiber long-term
      potentiation are still unknown. Using the fluorescent zinc probe N-(6-methoxy-8
      quinolyl)-para-toluenesulfonamide, we measured fast mossy fiber zinc changes
      indicating that zinc is released following single and low levels of electrical
      stimulation. The observed presynaptic zinc signals are maintained during the
      expression of mossy fiber long-term potentiation, assumed to be mediated by an
      increase in transmitter release, and are enhanced during paired-pulse
      facilitation. This zinc enhancement is, like paired-pulse facilitation, reduced
      during established long-term potentiation. The correlation between the paired
      pulse evoked zinc and field potential responses supports the idea that zinc is co
      released with glutamate.

PMID- 15476693
TI  - Neural progenitor cell transplants promote long-term functional recovery after
      traumatic brain injury.
AB  - Studies demonstrating the versatility of neural progenitor cells (NPCs) have
      recently rekindled interest in neurotransplantation methods aimed at treating
      traumatic brain injury (TBI). However, few studies have evaluated the safety and
      functional efficacy of transplanted NPCs beyond a few months. The purpose of this
      study was to assess the long-term survival, migration, differentiation and
      functional significance of NPCs transplanted into a mouse model of TBI out to 1
      year post-transplant. NPCs were derived from E14.5 mouse brains containing a
      transgene-expressing green fluorescent protein (GFP) and cultured as neurospheres
      in FGF2-containing medium. Neurospheres were injected into the ipsilateral
      striatum of adult C57BL/6 mice 1 week following unilateral cortical impact
      injury. Behavioral testing revealed significant improvements in motor abilities
      in NPC-treated mice as early as 1 week, and the recovery was sustained out to 1
      year post-transplant. In addition, mice receiving NPC transplants showed
      significant improvement in spatial learning abilities at 3 months and 1 year,
      whereas an intermediate treatment effect on this behavioral parameter was
      detected at 1 month. At 14 months post-transplant, GFP(+) NPCs were observed
      throughout the injured hippocampus and adjacent cortical regions of transplanted
      brains. Immunohistochemical analysis revealed that the majority of transplanted
      cells co-labeled for NG2, an oligodendrocyte progenitor cell marker, but not for
      neuronal, astrocytic or microglial markers. In conclusion, transplanted NPCs
      survive in the host brain up to 14 months, migrate to the site of injury, enhance
      motor and cognitive recovery, and may play a role in trophic support following
      TBI.

PMID- 15476694
TI  - Effect of systemic LPS injection on cortical NF-kappaB activity and inflammatory
      response following traumatic brain injury in rats.
AB  - The aim of current study is to investigate the effect of systemic administration
      of lipopolysaccharide (LPS) on the temporal pattern of cortical nuclear factor
      kappa B (NF-kappaB) binding activity, inflammatory response and secondary damage
      in the injured brain following traumatic brain injury (TBI). Right parietal
      cortical contusion in rats was made by using weight-dropping method. The rats
      were randomly divided into sham, LPS, TBI and TBI-LPS groups, with LPS injected
      intraperitoneally. NF-kappaB binding activity, cytokines, intercellular adhesion
      molecule-1 (ICAM-1) and brain damage were detected by electrophoretic mobility
      shift assay (EMSA), enzyme-linked immunosorbent assay (ELISA),
      immunohistochemistry and terminal deoxynucleotidyl-transferase-mediated biotin
      dUTP nick end labeling (TUNEL) apoptosis, respectively. The results showed that
      systemic administration of LPS following TBI could induce an immediate, strong
      and persistent upregulation of NF-kappaB, tumor necrosis factor-alpha (TNF
      alpha), interleukin-6 (IL-6) and ICAM-1 in the area surrounding the injured
      brain. As compared with rats of sham, LPS and TBI groups, NF-kappaB binding
      activity, TNF-alpha and IL-6 were significantly upregulated in the surrounding
      cortex of injured site as early as 3 h postinjury when challenged with LPS, kept
      at high level up to 7-days postinjury. ICAM-1-positive vessels and apoptotic
      TUNEL-positive cells in the injured brain were also significantly increased in
      TBI-LPS rats. It was concluded that inflammatory response and secondary brain
      damage occurred in the injured brain could be highly exacerbated by endotoxemia.

PMID- 15476695
TI  - A link between hyperbilirubinemia, oxidative stress and injury to neocortical
      synaptosomes.
AB  - Cytotoxicity by unconjugated bilirubin involves disturbances of membrane
      structure, excitotoxicity and cell death. These events were reported to trigger
      elevated free radicals production and impairment of calcium homeostasis, and to
      result in loss of cell membrane integrity. Therefore, this study was designed to
      investigate whether interaction of clinically relevant concentrations of free
      unconjugated bilirubin with synaptosomal membrane vesicles could be linked to
      oxidative stress, cytosolic calcium accumulation and perturbation of membrane
      function. Synaptosomal vesicles were prepared from gerbil cortical brain tissue
      and incubated with purified bilirubin (<or=1 microM), for 4 h at 37 degrees C.
      Intracellular concentrations of reactive oxygen species (ROS) and calcium were
      determined by dichlorofluorescin and BAPTA fluorescent probes, respectively.
      Membrane protein and lipid oxidation were evaluated by immunocytochemistry and
      phosphatidylserine exposure by annexin V binding. Levels of reduced and oxidized
      glutathione (GSH and GSSG, respectively), as well as activities of Mg(2+)-ATPase
      aminophospholipid translocase (flippase) and Na(+),K(+)-ATPase, were also
      measured. Our results showed that bilirubin induced oxidative stress, due to a
      rise in lipid (>or=10%, P<0.05) and protein oxidation (>or=20%, P<0.01), ROS
      content (approximately 17%, P<0.01), and a decrease in GSH/GSSG ratio (>30%,
      P<0.01). In addition, synaptosomes exposed to bilirubin exhibited increased
      externalization of phosphatidylserine (approximately 10%, P<0.05), together with
      decreased flippase and NA(+),K(+)-ATPase (>or=15%, P<0.05) activities, events
      that were accompanied by enhanced intracellular calcium levels ( approximately
      20%, P<0.01). The data obtained point out that interaction of unconjugated
      bilirubin with synaptosomal membrane vesicles leads to oxidative injury, loss of
      membrane asymmetry and functionality, and calcium intrusion, thus potentially
      contributing to the pathogenesis of encephalopathy by hyperbilirubinemia.

PMID- 15476696
TI  - Electron microscopic localisation of P2X4 receptor subunit immunoreactivity to
      pre- and post-synaptic neuronal elements and glial processes in the dorsal vagal
      complex of the rat.
AB  - P2X receptors are ligand gated ion channels activated by extracellular ATP. There
      are seven P2X subunits, P2X(1-7), and all are expressed in the CNS. The P2X(4)
      receptor subunit (P2X(4)R) is likely to be important in the CNS as it has been
      reported to be expressed throughout the brain and spinal cord. However, P2X(4)Rs
      have been identified as restricted to neurones, only in glia or expressed in both
      neurones and glia with no discernible relationship to CNS region or epitope
      target of antibodies used for staining. In addition, although there are
      particularly high levels of mRNA encoding P2X(4)R in the brainstem, previous
      immunohistochemical studies have revealed only indistinct staining. We therefore
      examined the distribution of P2X(4)R in the dorsal vagal complex (DVC) of the
      brainstem using immunohistochemistry in sections obtained from adult Wistar rats
      transcardially perfused with aldehyde fixatives. When this revealed staining
      identifiable only as small puncta at the light microscope level, we examined the
      area with electron microscopy. This ultrastructural study revealed that P2X(4)R
      immunoreactivity (IR) was present in neurones at both pre- and post-synaptic
      sites as well as in glial cell processes and somata. This P2X(4)R-IR was
      localised adjacent to plasma membranes, as well as internally in membrane bound
      structures resembling endosomes. Immunoreactivity in endosomes was more prominent
      following antigen retrieval protocols. Localisation of P2X(4)R-IR in astrocytes,
      identified by the presence of glial fibrillary acidic protein (GFAP), was
      confirmed using immunofluorescence. The presence of P2X(4)Rs in the dorsal vagal
      complex is consistent with expression studies, but some reasons for a lack of
      correlation with pharmacological studies are discussed. The P2X(4)R is therefore
      expressed by neurones and glia in the dorsal vagal complex and may play a role in
      mediating extracellular signalling by ATP in this region.

PMID- 15476697
TI  - Reciprocal connections between subdivisions of the dorsal raphe and the nuclear
      core of the locus coeruleus in the rat.
AB  - The interconnection between two brainstem monoaminergic nuclei, the dorsal raphe
      (DR) and the locus coeruleus (LC), was analyzed in the rat using retrograde
      tracing and immunocytochemistry. Gold-conjugated and inactivated wheatgerm
      agglutinin-horseradish peroxidase (WGA-apo-HRP-gold) was injected into
      subdivisions of the DR or rostro-caudal levels of the nuclear core of the LC, and
      labeled LC or DR neurons were identified by dopamine-beta-hydroxylase (DBH) or 5
      hydroxytryptamine (5-HT) immunostaining, respectively. Within the LC-DR
      projection, the caudal principal LC projected to the caudal, ventromedial, and
      interfascicular DR. Mid-LC as well as caudal LC projected with an ipsilateral
      predominance to the lateral wing subdivision of the DR. A few rostral LC neurons
      projected to caudal, dorsomedial, and ventromedial DR. Within the DR-LC
      projection, the rostral LC received inputs mainly from the caudal, dorsomedial,
      and ventromedial DR. Mid-LC to caudal LC received projections from mid-DR to
      caudal DR, with the heaviest projection from the ipsilateral lateral wing as well
      as caudal DR. The DR-LC projection was substantially more robust than LC-DR and
      included both serotonergic and nonserotonergic components. Thus, the data
      demonstrate topographically ordered, reciprocal connectivity between DR and LC
      with particularly strong projections from DR to LC. Communication between these
      two brainstem monoaminergic nuclei may be critical for a variety of functions
      including sleep-wake regulation, vigilance, analgesia, cognition, and stress
      responses.

PMID- 15476698
TI  - Central migration of neuronal tissue and embryonic stem cells following
      transplantation along the adult auditory nerve.
AB  - The regeneration of the auditory nerve remains a challenge in restoring hearing.
      An interesting approach would be to use a cell replacement therapy with the
      potential to establish connections from the inner ear to the central auditory
      system. This hypothesis was tested by xenografted (mouse to rat) implantation of
      embryonic dorsal root ganglion (DRG) neurons and embryonic stem (ES) cells along
      the auditory nerve in the adult host. DRG neurons were obtained at embryonic day
      13-14 in transgenic animals expressing enhanced green fluorescence protein
      (EGFP). For embryonic stem cells, a tau-GFP ES cell line was used as a donor. The
      fibers of the auditory nerve in the adult rat were transected through the
      modiolus at the first cochlear turn, and the biological implants were
      transplanted into the transection. The transplanted DRG neurons and ES cells
      survived for a postoperative survival time ranging from 3 to 9 weeks, verified by
      EGFP/GFP fluorescence, and neurofilament or TUJ1 immunostaining. At 9 weeks
      following implantation, the implanted DRG neurons were found to have migrated
      along the auditory nerve in the internal meatus. At the same postoperative time,
      the ES cells had migrated into the brain stem close to the ventral cochlear
      nucleus. The results demonstrate not only the survival and migration of
      xenografted DRG neurons and stem cells along the adult auditory nerve but also
      the feasibility of a cell replacement therapy in the degenerated auditory system.

PMID- 15476699
TI  - The adenosine kinase inhibitor ABT-702 augments EEG slow waves in rats.
AB  - ABT-702 is a novel and selective non-nucleoside adenosine kinase (AK) inhibitor
      that produces increases in endogenous extracellular adenosine. Adenosine (ADO) is
      thought to be an important neuromodulator of sleep, therefore, the effects of ABT
      702 and AK inhibition were examined on rat EEG and sleep, and compared to ADO
      receptor agonists to further evaluate the role of ADO receptor activation on
      sleep related EEG patterns. ABT-702 (10.0-30.0 micromol/kg, i.p.) increased the
      amplitude of the 1-4 Hz band (Fast Fourier Transform (FFT) analysis, p<0.05),
      which is indicative of augmented sleep-related slow waves. Theophylline (5.0
      micromol/kg, i.p.), a centrally active, non-selective adenosine receptor
      antagonist, attenuated the effects of ABT-702 (20.0 micromol/kg, i.p.) on EEG,
      whereas 8-(p-sulfophenyl)-theophylline (8-PST, 150.0 micromol/kg, i.p.), a
      peripherally active antagonist, did not, indicating that the EEG effects of ABT
      702 are mediated by a central ADO receptor mechanism. The selective A(1) agonist
      N6-cyclopentyladenosine (CPA, 30.0 micromol/kg, i.p.) also increased the
      amplitude of 1-4 Hz band, but was not as efficacious as ABT-702. In contrast, the
      A(2A) agonist CGS-21680 (1.0-10.0 micromol/kg, i.p.) and the non-selective
      agonist, N(6)-ethylcarboximidoadenosine (NECA, 0.03-0.1 micromol/kg, ip.),
      lowered 1-4 Hz amplitude for 2 h after injection. Finally, ABT-702 (10.0
      micromol/kg, i.p.) was found to significantly increase slow wave sleep and
      decrease REM sleep in rats implanted with both EEG and EMG electrodes for
      evaluation of sleep. These studies demonstrate that increased extracellular
      adenosine through AK inhibition can elicit modulatory effects on EEG slow waves
      via an interaction with central ADO receptor subtypes.

PMID- 15476700
TI  - Quantitative analysis of axon collaterals of single superficial pyramidal cells
      in layer IIb of the piriform cortex of the guinea pig.
AB  - To understand the functional organization of the piriform cortex (PC), the axon
      collaterals of three pyramidal cells in layer IIb of the anterior PC and one
      pyramidal cell in layer IIb of the posterior PC were labeled and quantitatively
      analyzed by intracellular biocytin injection in the guinea pig. Single pyramidal
      cells in the anterior and posterior PCs have widely distributed axon collaterals,
      which exhibit little tendency for patchy concentrations inside as well as outside
      the PC. The total lengths of the axon collaterals of the three fully analyzed
      pyramidal cells ranged from 68 to 156 mm, more than 50% of which were distributed
      in the PC. The total number of boutons of the three cells ranged from 6000 to
      14,000, 5000-7000 of which were distributed in the PC. It was estimated that
      individual pyramidal cells in layer IIb form synaptic contacts with 2200 to 3000
      other pyramidal cells in the PC, indicating that single pyramidal cells in layer
      IIb receive input from a large number of other pyramidal cells. This high
      connectivity of the network of pyramidal cells in the PC can be regarded as the
      neural network operating parallel distributed processing, which may play an
      important role in experience-induced enhancement in odorant discrimination in the
      PC.

PMID- 15476701
TI  - Neuroprotective and neurotrophic effect of apomorphine in the striatal 6-OHDA
      lesion rat model of Parkinson's disease.
AB  - We investigated the possible neuroprotective effect of the dopamine (DA) receptor
      agonist R-apomorphine (R-APO) within the striatal 6-hydroxydopamine (6-OHDA) rat
      model of Parkinson's disease. In one group of rats, R-APO administration (10
      mg/kg/day, s.c.) started 15 min before 6-OHDA-injection. In a second group, R-APO
      administration started 24 h after lesion induction. Both groups received R-APO
      chronically for 11 days. Testing was carried out 2 weeks post-lesioning. R-APO
      treatment, whether started before or after the lesion induction, significantly
      reduced both the amphetamine-induced ipsiversive rotation and the size of the
      lesion at the level of the substantia nigra. Moreover, the dopamine cell shape
      and size resembled that observed in intact animals. R-APO treatment had no effect
      on the number of cells in the substantia nigra of intact rats, but significantly
      increased the number of cells in the ventral tegmental area (VTA), suggesting
      selective neurotrophic properties of R-APO in this region. R-APO treatment
      significantly attenuated the 6-OHDA-induced striatal DA depletion and DOPAC/DA
      ratios were normalized. Finally, an acute injection of 10 mg/kg R-APO was unable
      to scavenge 6-OHDA or MPP(+)-induced hydroxyl radicals as determined with the in
      vivo salicylate trapping technique. These data provide further evidence of the
      neurorescuing properties of R-APO. At least at the dose used in this study, this
      effect possibly occurs via mechanisms other than scavenging of hydroxyl radicals.
      In intact rats, we also show neurotrophic effects of the R-APO treatment. These
      seem to be limited to the VTA.

PMID- 15476702
TI  - Spinal neurons activated with the urethrogenital reflex in the male rat.
AB  - The urethrogenital (UG) reflex is a spinal ejaculatory-like reflex. The location
      of spinal neurons activated by the UG reflex was examined in the male rat using
      the immediate early gene, c-fos. In addition, co localization of neurons
      containing galanin and choline acetyl transferase (ChAT) and serotonin fibers
      with fos-immunoreactive (fos-I) nuclei was examined. Activation of the UG reflex
      resulted in a significant increase in fos positive nuclei in segments T13-S1,
      compared to controls in which the UG reflex was not activated. Spinal circuits
      involved in the UG reflex include neurons relaying afferent information from the
      pudendal sensory nerve, in the dorsal horn and medial cord of L5-S1. Interneurons
      specifically activated with the UG reflex were identified in the medial,
      intermediate and lateral gray. A small proportion of parasympathetic and
      sympathetic preganglionic neurons in the intermediolateral cell column (IML) of
      L5-S1 and IML and medial gray of T13-L2, respectively, was activated with the UG
      reflex. A significant increase in the number of galanin containing neurons
      expressing c-fos in the medial gray of L3-L4 was also observed with the UG
      reflex. Serotonin fibers and varicosities were found throughout the spinal cord
      and were especially dense in the ventral horn, IML and medial gray. Fos activated
      neurons were found in close apposition to serotonin fibers in the IML and medial
      gray. These studies demonstrate the multisegmental intraspinal circuitry
      responsible for ejaculatory-like responses and demonstrate the potential
      involvement of galanin, acetylcholine and serotonin in mediation of the UG
      reflex.

PMID- 15476703
TI  - Inactivation of glycogen synthase kinase-3beta protects against kainic acid
      induced neurotoxicity in vivo.
AB  - Many neurodegenerative diseases involve oxidative stress and excitotoxic cell
      death. In an attempt to further elucidate the signal transduction pathways
      involved in the cell death/cell survival associated with excitotoxicity, we have
      used an in vivo model of excitotoxicity employing kainic acid (KA)-induced
      neurotoxicity. Here, we show that extracellular signal-related kinase (ERK) 2,
      but not ERK 1, is phosphorylated and thereby activated in the hippocampus and
      cerebellum of kainic acid-treated mice. Phosphorylation and hence inactivation of
      glycogen synthase kinase 3beta (GSK-3beta), a general survival factor, is often a
      downstream consequence of mitogen-activated protein kinase pathway activation.
      Indeed, GSK-3beta phosphorylation occurred in response to kainic acid exclusively
      in the affected hippocampus, but not as a consequence of ERK activation. This may
      represent a compensatory attempt at self-protection by the cells in this
      particular brain region. A role for GSK-3beta inhibition in cell survival was
      further supported by the fact that pharmacological inhibition of GSK-3beta using
      lithium chloride was protective against kainic acid-induced excitotoxicity in
      hippocampal slice cultures. This work supports a role for GSK-3beta in cell death
      in response to excitotoxins in vivo and further confirms that GSK-3beta plays a
      role in cell death/cell survival pathways.

PMID- 15476704
TI  - Preserved ipsilateral-to-lesion motor map organization in the unilateral 6-OHDA
      treated rat model of Parkinson's disease.
AB  - The classic view of dopamine (DA) loss in Parkinson's disease is that it produces
      a functional deafferentation in striatal-cortical circuitry that, in turn,
      contributes to sensorimotor deficits. The present study examines this view in the
      rat by assessing how DA-depletion affects the intracortical microstimulation
      (ICMS) topographic representation of movement in the rostral and caudal motor
      areas of the motor cortex. The ICMS map is used as an index of motor cortex
      function because it has been shown to reflect motor function and experience.
      Groups of rats received no training or skilled reach training and were then given
      unilateral 6-hydroxydopamine (6-OHDA) or sham lesions of the nigrostriatal bundle
      to deplete nigrostriatal DA. Lesion success was confirmed by abnormalities in
      skilled reaching, by apomorphine-induced rotation, and by loss of DA neurons in
      the substantia nigra. The size and threshold of the motor map in naive and
      skilled reach trained DA-depleted rats were preserved. In addition, there was an
      increase in distal limb representation in the caudal forelimb area (CFA) in the
      DA-depleted rats suggesting a possible plastic response to the behavioral effects
      of DA-depletion. The presence of preserved size and modified map organization in
      DA-depleted rats is discussed in relation to the hypothesis that preserved motor
      cortex functionality despite DA loss underlies the spared motor abilities of DA
      depleted rats.

PMID- 15476705
TI  - Somatostatin inhibition of fictive respiration is modulated by pH.
AB  - We studied the respiratory effects of the tetradecapeptide somatostatin (SST)
      upon fictive respiration using the in vitro brain stem spinal cord preparation
      from new-born mouse. We found that SST inhibits respiration, an effect that was
      potentiated when the chemical drive to respiration was increased. SST inhibited
      fictive respiration decreasing both the frequency and amplitude in a dose
      dependent way. SST inhibition was not antagonized by cyclosomatostatin (cyclo [7
      aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)]), a putative SST antagonist, which in
      contrast behaved as a partial agonist. When the chemical drive to respiration was
      increased, by lowering the pH of the brain stem superfusion medium from 7.4 to
      7.3, the inhibitory effect of SST on respiratory frequency was potentiated. These
      results suggest an interaction between SST and respiratory central chemoreception
      in new-born mouse.

PMID- 15476706
TI  - Corticotropin-releasing factor gene expression is down-regulated in the central
      nucleus of the amygdala of alcohol-preferring rats which exhibit high anxiety: a
      comparison between rat lines selectively bred for high and low alcohol
      preference.
AB  - The role of amygdaloid corticotropin-releasing factor (CRF) in alcoholism is not
      clear. Alcohol-preferring (P) rats and high alcohol-drinking (HAD) rats are
      selectively bred for high alcohol preference, and have been considered suitable
      animal models for studying alcoholism. The CRF neurons in the central nucleus of
      the amygdala (CeA) of P rats and HAD rats were studied in comparison with those
      of their respective counterparts, namely, alcohol-nonpreferring (NP) rats and low
      alcohol-drinking (LAD) rats. Specifically, CRF-immunoreactivity (ir) in the CeA
      and paraventricular hypothalamic nucleus (PVN) was assessed using
      radioimmunohistochemical (RIH) assay in alcohol-naive P/NP rats, and HAD/LAD
      rats. Furthermore, CRF mRNA was examined using in situ hybridization in the CeA
      of P/NP rats. Anxiety levels were also evaluated using an elevated plus maze.
      Results of the present study showed that CRF-ir was significantly lower in the
      CeA of P rats than NP rats. Moreover, CRF mRNA in the CeA was also much lower in
      P rats than NP rats. Such differences were not seen in the PVN. Interestingly,
      those P rats exhibited higher anxiety than NP rats. In contrary, there were no
      innate differences of CRF-ir in both the CeA and PVN between HAD and LAD rats
      whose anxiety levels were similar. This study is consistent with the literature
      showing CRF knockout (KO) induces alcohol drinking, and central administrations
      of CRF reduce alcohol intake. Collectively, the present study suggests that
      reduced CRF gene expression in the CeA of P rats is associated with their alcohol
      preference and anxiety.

PMID- 15476707
TI  - Neuropeptide PACAP inhibits hypoxic activation of brain microglia: a protective
      mechanism against microglial neurotoxicity in ischemia.
AB  - Hypoxia is one of the important physiological stimuli that are often associated
      with a variety of pathological states such as ischemia, respiratory diseases, and
      tumorigenesis. In the central nervous system, hypoxia that is accompanied by
      cerebral ischemia not only causes neuronal cell injury, but may also induce
      pathological microglial activation. We have previously shown that hypoxia induces
      inflammatory activation of cultured microglia and their inducible nitric oxide
      synthase induction via p38 mitogen-activated protein kinase (MAPK) pathway, and a
      neuropeptide PACAP selectively inhibits microglial signal transduction. Based on
      these findings, we hypothesized that the neuropeptide may inhibit the hypoxic
      activation of microglia, and this may provide a neuroprotection against
      inflammation-induced neuronal injury. When this possibility was tested using
      cultured microglia and PC12 cells, we found that PACAP attenuates inflammatory
      activation of microglia under hypoxic condition, and protects cocultured PC12
      cells from microglial neurotoxicity. In addition, the neuropeptide reduced the
      hypoxia-induced activation of p38 MAPK, indicating that the p38 MAPK is a
      molecular target of the PACAP action in microglia. The neuroprotective effects of
      PACAP in animal models of cerebral hypoxia/ischemia may be partly due to its
      direct actions on brain microglia and neurotoxic inflammation.

PMID- 15476708
TI  - Intramolecular aldol cyclization of C-4-ulopyranosyl-2'-oxoalkanes controlled by
      steric effects. Asymmetric synthesis of substituted 8-oxabicyclo[3.2.1]octanones
      and -octenones and cyclopentenones.
AB  - Whereas C-2- and 4-ulopyranosyl compounds (C-2- and C-4-ulosides) can be
      converted to cyclopentenones under base conditions through beta-elimination and
      ring contraction, base-initiated beta-elimination of C-glycosyl 2'-aldehydes and
      2'-ketones results in the formation of acyclic alpha,beta-unsaturated aldehydes
      or ketones. By combining both molecular features we synthesized 1-C-(4
      ulopyranosyl)-2-oxoalkanes 6, 13, and 20 and investigated their reactions when
      they were treated with base. Both alpha- and beta-anomers of C-(4
      ulopyranosyl)acetaldehydes 6 and 13 underwent a fast intramolecular aldol
      reaction between the C-5 enolate and 2'-aldehyde to form optically pure 8
      oxabicyclo[3.2.1]octanones, which further transformed to 8
      oxabicyclo[3.2.1]octenones 14 and 15 by beta-elimination. However, this aldol
      reaction did not occur when 1-C-(4-ulopyranosyl)propan-2-one 20 was treated with
      base because of steric hindrance exerted by the additional methyl group. Instead,
      an alternate C-3 enolization led to beta-elimination and further electro-ring
      opening to form an acyclic enol, which was then converted through a disrotatory
      intramolecular aldol cyclization to a cis-substituted cyclopentenone 21.

PMID- 15476709
TI  - The synthesis of a series of modified mannotrisaccharides as probes of the
      enzymes involved in the early stages of mammalian complex N-glycan formation.
AB  - A series of mannotrisaccharides were synthesized by two distinct chemical
      pathways as probes of the enzymes involved in the early stages of mammalian
      complex N-glycan formation. Methyl (alpha-D-mannopyranosyl)-(1-->3)-[(alpha-D
      mannopyranosyl)-(1-->6)]-beta-D-mannopyranoside (6) and methyl (2-deoxy-2-fluoro
      alpha-D-mannopyranosyl)-(1-->3)-[(2-deoxy-2-fluoro-alpha-D-mannopyranosyl)-(1-
      >6)]-beta-D-mannopyranoside (8) were rapidly synthesized from unprotected methyl
      beta-D-mannopyranoside (12). Methyl (2-deoxy-2-fluoro-alpha-D-mannopyranosyl)-(1-
      >3)-[(alpha-D-mannopyranosyl)-(1-->6)]-beta-D-mannopyranoside (7) and methyl
      (alpha-D-mannopyranosyl)-(1-->3)-[(2-deoxy-2-fluoro-alpha-D-mannopyranosyl)-(1-
      >6)]-beta-D-mannopyranoside (9) were synthesized from the common orthogonally
      protected precursor methyl 2-O-acetyl-4,6-O-benzylidene-beta-D-mannopyranoside
      (15). The 2-deoxy-2-fluoro substitution common to trisaccharides 7-9 renders
      these analogues resistant to enzyme action in two distinct ways. Firstly the
      fluorine serves as a non-nucleophilic isostere for the acceptor hydroxyl in
      studies with glycosyl transferases GnT-I and GnT-II (7 and 9, respectively).
      Secondly it should render trisaccharide 8 stable to hydrolysis by the
      mannosidases Man-II and Man-III by inductive destabilization of their
      oxocarbenium ion-like transition states. These analogues should be useful for
      structural studies on these enzymes.

PMID- 15476710
TI  - Synthesis of an alpha-linked dimer of the trisaccharide repeating unit of the
      exopolysaccharide produced by Pediococcus damnosus 2.6.
AB  - A hexasaccharide, beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->2)]-alpha-D-Glcp-(1-->3)
      beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->2)]-D-Glcp, the alpha-linked dimer of the
      trisaccharide repeating unit of the exopolysaccharide produced by Pediococcus
      damnosus 2.6, was synthesized as its methyl glycoside. Condensation of fully
      benzoylated alpha-D-glucopyranosyl trichloroacetimidate (1) with isopropyl 4,6-O
      benzylidene-1-thio-beta-D-glucopyranoside (2) selectively furnished (1-->3)
      linked disaccharide 3, and subsequent 2-O-acetylation, desulfation, and
      trichloroacetimidate formation afforded the disaccharide donor 6. Meanwhile,
      selective 3-O-coupling of methyl 4,6-O-benzylidene-alpha-d-glucopyranoside (8)
      with 3-O-allyl-2,4,6-tri-O-benzoyl-alpha-D-glucopyranosyl trichloroacetimidate
      (7), followed by coupling with 1 gave the trisaccharide 10. Removal of the
      benzylidene group of 10, benzoylation, and deallylation produced the
      trisaccharide acceptor 12. Condensation of 12 with 6 yielded a pentasaccharide
      mixture 13 with beta and alpha isomers in a ratio of 2:1. Removal of the
      benzylidene group of 13, followed by benzoylation gave the pentasaccharide
      mixture 14. Selective 2'''-deacetylation of the isolated beta-linked 14beta with
      MeCOCl/MeOH/CH2Cl2 did not give the expected pentasaccharide acceptor, and
      serious decomposition occurred, indicating a large steric hindrance at C-2'''.
      Alternatively, 2,3-di-O-glycosylation of allyl 4,6-O-benzylidene-beta-D
      glucopyranoside (21) with 1 gave 22, then deallylation and trichloroacetimidate
      formation afforded the trisaccharide donor 24. Condensation of 12 with 24
      furnished only the alpha-linked hexasaccharide 25, and its deprotection gave the
      free hexaoside 27.

PMID- 15476711
TI  - Synthesis of a disaccharide fragment of rhamnogalacturonan II.
AB  - A disaccharide portion of the A-side chain of the rhamnogalacturonan II
      oligosaccharide has been prepared. Glycosylation of methyl (methyl 3,4-O
      isopropylidene-alpha-D-galactopyranosid)uronate with p-tolyl 2,3-di-O-acetyl-3-C
      (benzyloxymethyl)-1-thio-alpha/beta-D-erythrofuranoside was carried out using N
      iodosuccinimide as promoter and silver trifluoromethanesulfonate as catalyst.
      Removal of the protecting groups gave the beta-d-Apif-(1-->2)-alpha-D-GalpA-OMe
      disaccharide.

PMID- 15476712
TI  - Preparation of low-molecular-weight and high-sulfate-content chitosans under
      microwave radiation and their potential antioxidant activity in vitro.
AB  - In the present paper microwave radiation has been used to introduce N-sulfo and O
      sulfo groups into chitosan with a high degree of substitution and low-molecular
      weight. The sulfation of chitosan was performed in microwave ovens. It was found
      that microwave heating is a convenient way to obtain a wide range of products of
      different degrees of substitution and molecular weight only by changing reaction
      time or/and radiation power. Moreover, microwave radiation accelerated the
      degradation of sulfated chitosan, and the molecular weight of sulfated chitosan
      was considerably lower than that obtained by traditional heating. There are no
      differences in the chemical structure of sulfated chitosan obtained by microwave
      and by conventional technology. FTIR and 13C NMR spectral analyses demonstrated
      that a significantly shorter time is required to obtain a satisfactory degree of
      substitution and molecular weight by microwave radiation than by conventional
      technology. In this present paper, we also determined antioxidant activity of low
      molecular-weight and high-sulfate-content chitosans (LCTS). The results showed
      LCTS could scavenge superoxide and hydroxyl radical. Its IC50 is 0.025 and 1.32
      mg/mL, respectively. It is a potential antioxidant in vitro.

PMID- 15476713
TI  - The O-acetylation patterns in the O-antigens of Hafnia alvei strains PCM 1200 and
      1203, serologically closely related to PCM 1205.
AB  - Serological tests revealed immunochemical similarities between the
      lipopolysaccharides of Hafnia alvei strains PCM 1200, 1203 and 1205.
      Immunoblotting and ELISA showed cross-reactions between the strains. NMR
      spectroscopy showed that the O-deacetylated O-specific polysaccharides isolated
      from lipopolysaccharides of H. alvei strains PCM 1200 and 1203 possessed the same
      composition and sequence as the O-deacetylated O-specific polysaccharide of H.
      alvei strain PCM 1205, that is a glycerol teichoic-acid-like polymer with a
      repeating unit of the following structure: [carbohydrate structure: see text] NMR
      spectroscopic studies of the polysaccharides concluded that O-3 of the side chain
      beta-D-GlcpNAc is partially O-acetylated (50-80%) in both investigated strains.
      In strain PCM 1203 an additional O-acetyl group (50-80%) is linked to O-6 of the
      chain -->3)-alpha-D-GlcpNAc-(1--> residue. The structural features of the
      isolated O-specific polysaccharides were also the same as those of the O-specific
      polysaccharides on the bacterial cells directly observed by the HR-MAS NMR
      technique.

PMID- 15476714
TI  - Impact and efficiency of GH10 and GH11 thermostable endoxylanases on wheat bran
      and alkali-extractable arabinoxylans.
AB  - The results of a comparative study of two thermostable (1-->4)-beta-xylan
      endoxylanases using a multi-technical approach indicate that a GH11 xylanase is
      more useful than a GH10 xylanase for the upgrading of wheat bran into soluble
      oligosaccharides. Both enzymes liberated complex mixtures of
      xylooligosaccharides. 13C NMR analysis provided evidence that xylanases cause the
      co-solubilisation of beta-glucan, which is a result of cell-wall disassembly. The
      simultaneous use of both xylanases did not result in a synergistic action on
      wheat bran arabinoxylans, but instead led to the production of a product mixture
      whose profile resembled that produced by the action of the GH10 xylanase alone.
      Upon treatment with either xylanase, the diferulic acid levels in residual bran
      were unaltered, whereas content in ferulic and p-coumaric acids were unequally
      decreased. With regard to the major differences between the enzymes, the products
      resulting from the action of the GH10 xylanase were smaller in size than those
      produced by the GH11 xylanase, indicating a higher proportion of cleavage sites
      for the GH10 xylanase. The comparison of the kinetic parameters of each xylanase
      using various alkali-extractable arabinoxylans indicated that the GH10 xylanase
      was most active on soluble arabinoxylans. In contrast, probably because GH11
      xylanase can better penetrate the cell-wall network, this enzyme was more
      efficient than the GH10 xylanase in the hydrolysis of wheat bran. Indeed the
      former enzyme displayed a nearly 2-fold higher affinity and a 6.8-fold higher
      turnover rate in the presence of this important by-product of the milling
      industry.

PMID- 15476715
TI  - Complementary exploration of the action pattern of hyaluronate lyase from
      Streptococcus agalactiae using capillary electrophoresis, gel-permeation
      chromatography and viscosimetric measurements.
AB  - Hyaluronic acid (HA) was treated with hyaluronate lyase (GBS HA lyase, E.C.
      4.2.2.1, from Streptococcus agalactiae strain 4755), and the products have been
      analyzed by capillary electrophoresis (CE-UV and online CE-ESIMS), gel-permeation
      chromatography (GPC) and viscosimetric measurements. The resulting
      electropherograms showed that the enzyme produced a mixture of oligosaccharides
      with a 4,5-unsaturated uronic acid nonreducing terminus. More exhaustive
      degradation of HA led to increasing amounts of di-, tetra-, hexa-, octa- and
      decasaccharides. Using CE, linear relationships were found between peak area of
      the observed oligosaccharides and reaction time. Determination of viscosity at
      different stages of reaction yielded an initial rapid decrease following
      Michaelis-Menten theory. A reaction time-dependent change in the elution position
      of the HA peak due to partial digestion of HA with GBS hyaluronate lyase has been
      observed by GPC. These results indicated that the HA lyase under investigation is
      an eliminase that acts in a nonprocessive endolytic manner, as at all stages of
      digestion a mixture of oligosaccharides of different size were found. For GBS HA
      lyase from Streptococcus agalactiae strain 3502, previously published findings
      reported an action pattern that involves an initial random endolytic cleavage
      followed by rapid exolytic and processive release of unsaturated disaccharides.
      Our results suggest that differences between the two enzymes from distinct S.
      agalactiae strains (GBS strains 4755 and 3502) have to be considered.

PMID- 15476716
TI  - Metal-ion environment in solid Mn(II), Co(II) and Ni(II) hyaluronates.
AB  - Amorphous powders and films of some metal hyaluronate complexes of general
      composition (C14H20O11N)2 x xH2O (M = Mn2+, Ni2+ and Co2+) have been prepared at
      pH 5.5-6.0. The coordination geometry around the metal ions has been analyzed by
      EXAFS (extended X-ray absorption fine structure) and FTIR spectroscopy. Mn2+,
      Ni2+, and Co2+ ions are coordinated to carboxylate oxygen atoms and water
      molecules. The process of local geometry formation round the metal ions is
      sensitive to sample preparation.

PMID- 15476717
TI  - Purification, structure and immunobiological activity of an arabinan-rich pectic
      polysaccharide from the cell walls of Prunus dulcis seeds.
AB  - The structure and bioactivity of a polysaccharide extracted and purified from a
      4M KOH + H3BO3 solution from Prunus dulcis seed cell wall material was studied.
      Anion-exchange chromatography of the crude extract yielded two sugar-rich
      fractions: one neutral (A), the other acidic (E). These fractions contain a very
      similar monosaccharide composition: 5:2:1 for arabinose, uronic acids and xylose,
      respectively, rhamnose and galactose being present in smaller amounts. As
      estimated by size-exclusion chromatography, the acidic fraction had an apparent
      molecular mass of 762 kDa. Methylation analysis (from the crude and fractions A
      and E), suggests that the polysaccharide is an arabinan-rich pectin. In all
      cases, the polysaccharides bear the same type of structural Ara moieties with
      highly branched arabinan-rich pectic polysaccharides. The average relative
      proportions of the arabinosyl linkages is 3:2:1:1 for T-Araf:(1-->5)-Araf:(1-
      >3,5)-Araf:(1-->2,3,5)-Araf. The crude polysaccharide extract and fractions A and
      E induced a murine lymphocyte stimulatory effect, as evaluated by the in vitro
      and in vivo expression of lymphocyte activation markers and spleen mononuclear
      cells culture proliferation. The lymphocyte stimulatory effect was stronger on B-
      than on T-cells. No evidence of cytotoxic effects induced by the polysaccharide
      fractions was found.

PMID- 15476718
TI  - Correlation of structure to antitumor activities of five derivatives of a beta
      glucan from Poria cocos sclerotium.
AB  - A water-insoluble (1-->3)-beta-D-glucan isolated from fresh sclerotium of Poria
      cocos was, respectively, sulfated, carboxymethylated, methylated,
      hydroxyethylated, and hydroxypropylated, to afford five water-soluble
      derivatives. Their weight-average molecular masses (Mw) and intrinsic viscosities
      ([eta]) were determined by size-exclusion chromatography combined with laser
      light scattering (SEC-LLS), LLS, and viscometry in phosphate buffer solution
      (PBS) at 37 degrees C. The antitumor activities, against Sarcoma 180 tumor cell
      (S-180) and gastric carcinoma cell strain (MKN-45 and SGC-7901) of the native
      beta-glucan and the five derivatives, were tested in vitro and in vivo. The Mw
      values of the five derivatives in PBS were determined to be 3.8 x 10(4), 18.9 x
      10(4), 16.0 x 10(4), 76.8 x 10(4), and 224.3 x 10(4), respectively. The high Mw
      values of the hydroxyethylated and hydroxypropylated derivatives in aqueous
      solution resulted from aggregation, and their true Mw values obtained in dimethyl
      sulfoxide were 20.1 x 10(4) and 19.1 x 10(4). The sulfated and carboxymethylated
      derivatives having DS of 1.0-1.3 show good water solubility, and exist as
      relatively expanded chains in aqueous solution. Interestingly, the native beta
      glucan did not show antitumor activity, whereas the sulfated and
      carboxymethylated derivatives exhibit significant antitumor activities against S
      180 and gastric carcinoma tumor cells. This work showed that good water
      solubility, relatively high chain stiffness, and moderate molecular mass of the
      derivatives in aqueous solution contribute beneficial to enhancement of antitumor
      activity.

PMID- 15476719
TI  - The system of galactans of the red seaweed, Kappaphycus alvarezii, with emphasis
      on its minor constituents.
AB  - The galactans extracted with hot water from Kappaphycus alvarezii, after previous
      extraction at room temperature, are mainly composed of kappa-carrageenans
      (approximately 74%) and micro-carrageenans (approximately 3%). However, a
      significant percentage of these galactans (at least 14%) is composed of sulfated
      agarans and, possibly, agaran-type sulfated DL-hybrid galactans. These agarans
      are partially substituted on C-2 or C-4 or disubstituted on both positions of the
      beta-D-galactose units and on C-3 or C-2 and C-3 of the alpha-L-galactose
      residues with sulfate groups or single stubs of beta-D-xylopyranose, D
      glucopyranose, and galactose or with D-glucopyranosyl-(1-->4)-D-glucopyranose
      side chains. Significant quantities of 2-O-methyl- and 3-O-methyl-L-galactose
      units are also present. A great tendency to retain Ca2+ and Mg2+, in spite of
      massive treatments with Na+ and K+ salts, was observed. The complexation between
      agarans and agarans-kappa-carrageenans through divalent cations and the possible
      zipper-type carbohydrate-carbohydrate interactions would be two complementary
      mechanisms of interactions.

PMID- 15476720
TI  - Structure of a major glycolipid from Thermus oshimai NTU-063.
AB  - The structure of a major glycolipid isolated from the thermophilic bacteria
      Thermus oshimai NTU-063 was elucidated. The sugar and fatty acid compositions
      were determined by GC-MS and HPLC analysis on their methanolysis and methylation
      derivatives, respectively. After removal of both O- and N-acyl groups by alkaline
      treatment, the glycolipid was converted to a fully acetylated tetraglycosyl
      glycerol derivative, the structure of which was then determined by NMR
      spectroscopy (TOCSY, HSQC, HMBC). Thus, the complete structure of the major
      glycolipid from T. oshimai NTU-063 was established as beta-Glcp-(1-->6)-beta-Glcp
      (1-->6)-beta-GlcpNAcyl-(1-->2)-alpha-Glcp-(1-->1)-glycerol diester. The N-acyl
      groups on the 2-amino-2-deoxy-glucopyranose residue are C15:0 and C17:0 fatty
      acids, whereas the fatty acids of glycerol diester are more heterogeneous
      including both straight and branched fatty acids from C15:0 to C18:0.

PMID- 15476721
TI  - Syntheses of alkenylated carbohydrate derivatives toward the preparation of
      monolayers on silicon surfaces.
AB  - This note describes the synthesis of different alkenylated carbohydrate
      derivatives suitable for direct attachment to hydrogen-terminated silicon
      surfaces. The derivatives were alkenylated at the C-1 position, while the
      remaining hydroxyl groups were protected. The development of such new
      carbohydrate-based sensing elements opens the access to new classes of
      biosensors.

PMID- 15476722
TI  - Syntheses of monohydroxy benzyl ethers of polyols: tri-O-benzylpentaerythritol
      and other highly benzylated derivatives of symmetrical polyols.
AB  - Symmetrical polyols can be converted into benzyl ethers with one free hydroxyl
      group in good yield by reaction of the monodibutylstannylene acetal with excess
      benzyl bromide in the presence of tetrabutylammonium bromide and
      diisopropylethylamine in xylene. The reaction pathway involves initial
      benzylation of the dibutylstannylene acetal to give benzyl and
      bromodibutylstannyl ethers; if a hydroxyl group remains unsubstituted, the latter
      ether ring closes and reacts further.

PMID- 15476723
TI  - Environmentally friendly C-glycosylation of phloroacetophenone with unprotected D
      glucose using scandium(III) trifluoromethanesulfonate in aqueous media: key
      compounds for the syntheses of mono- and di-C-glucosylflavonoids.
AB  - The direct C-glycosylation of phloroacetophenone with an unprotected d-glucose in
      aqueous media using scandium(III) trifluoromethanesulfonate (Sc(OTf)3) as the
      catalyst, gave mono- and bis-C-beta-glycosylic compounds in highest total yield
      of 81%. The second and third use of the recovered Sc(OTf)3 afforded them in total
      yields of 56% and 53%, respectively.

PMID- 15476724
TI  - Simple syntheses of 4-O-glucosylated 1-deoxynojirimycins from maltose and
      cellobiose.
AB  - Glucosidase inhibitors alpha-D-glucopyranosyl-(1-->4)-1-deoxynojirimycin and beta
      D-glucopyranosyl-(1-->4)-1-deoxynojirimycin were prepared from maltose and
      cellobiose, respectively, via the corresponding 5,6-eno derivatives, their
      epoxidation and the subsequent double reductive amination of the resulting 5
      uloses. In both cases, the reported route is the first chemical synthesis not
      based on enzymatic glucosyl transfer.

PMID- 15476725
TI  - The structure of the O-polysaccharide from the lipopolysaccharide of Providencia
      stuartii O47.
AB  - The O-polysaccharide was obtained by mild acid degradation of the
      lipopolysaccharide of Providencia stuartii O47:H4, strain 3646/51. Studies by
      sugar and methylation analyses along with Smith degradation and 1H and 13C NMR
      spectroscopy, including two-dimensional 1H,1H COSY, TOCSY, ROESY and H-detected
      1H,13C HSQC and HMBC experiments, showed that the polysaccharide has a branched
      hexasaccharide repeating unit with the following structure: [carbohydrate
      structure: see text]

PMID- 15476726
TI  - Synthesis of polysaccharide-stabilized gold and silver nanoparticles: a green
      method.
AB  - A simple, green method was developed for the synthesis of gold and silver
      nanoparticles by using polysaccharides as reducing/stabilizing agents. The
      obtained positively charged chitosan-stabilized gold nanoparticles and negatively
      charged heparin-stabilized silver nanoparticles were characterized with UV-vis
      spectroscopy and transmission electron microscopy. The results illustrated the
      formation of gold and silver nanoparticles inside the nanoscopic polysaccharide
      templates. Moreover, the morphology and size distribution of prepared gold and
      silver nanoparticles varied with the concentration of both the polysaccharides
      and the precursor metal salts.

PMID- 15476727
TI  - Mucor hiemalis endo-beta-N-acetylglucosaminidase can transglycosylate a bisecting
      hybrid-type oligosaccharide from an ovalbumin glycopeptide.
AB  - We found that the recombinant endo-beta-N-acetylglucosaminidase of Mucor hiemalis
      (Endo-M) expressed in Candida boidinii had the transglycosylation activity of
      transferring a bisecting hybrid-type oligosaccharide from an ovalbumin
      glycopeptide to the acceptor (p-nitrophenyl 2-acetamido-2-deoxy-beta-D
      glucopyranoside) in a good yield of 43%.

PMID- 15476728
TI  - Daily intake of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans
      (PCDD/PCDFs) in foodstuffs consumed in Tarragona, Spain: a review of recent
      studies (2001-2003) on human PCDD/PCDF exposure through the diet.
AB  - Concentrations of polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated
      dibenzofurans (PCDF) were measured in foodstuffs randomly acquired in various
      locations of Tarragona County (Catalonia, Spain) in September 2002. A total of 36
      composite samples, belonging to various food groups (vegetables, fruits, meat and
      meat products, fish and seafood, cereals, pulses, milk, dairy products, eggs, and
      oils and fats) were analyzed by high-resolution gas chromatography/high
      resolution mass spectrometry. The dietary intake of PCDD/Fs was subsequently
      determined. For calculations, recent data on consumption of the selected food
      items were used. Total dietary intake of PCDD/Fs for the general population of
      Tarragona County was estimated to be 59.6 pg I-TEQ/day (63.8 pg WHO-TEQ/day).
      Fish and seafood (33.7%), oils and fats (15.3%), cereals (14.4%), and dairy
      products (13.7%) were the most important contributors to this intake. This PCDD/F
      intake is notably lower than the intake estimated in 1998 for the same
      geographical area, 210.1 pg I-TEQ/day. The current PCDD/F dietary intake is below
      the tolerable intake range of 1-4 pg TEQ/kg body weight/day established by the
      WHO in 1998. Finally, the current intake is compared with the dietary intakes of
      PCDD/Fs recently (2001-2003) reported for a number of regions and countries.

PMID- 15476729
TI  - Time-space modeling of journey-time exposure to traffic-related air pollution
      using GIS.
AB  - Journey-time exposures represent an important, though as yet little-studied,
      component of human exposure to traffic-related air pollution, potentially with
      important health effects. Methods for assessing journey-time exposures, either as
      part of epidemiological studies or for policy assessment, are, however, poorly
      developed. This paper describes the development and testing of a GIS-based system
      for modeling human journey-time exposures to traffic-related air pollution: STEMS
      (Space-Time Exposure Modeling System). The model integrates data on source
      activity, pollutant dispersion, and travel behavior to derive individual- or
      group-level exposure measures to atmospheric pollution. The model, which is
      designed to simulate exposures of people as they move through a changing air
      pollution field, was developed, validated, and trialed in Northampton, UK. The
      system currently uses ArcInfo to couple four separate submodels: a source
      activity/emission model (SATURN), a proprietary atmospheric dispersion model
      (ADMS-Urban), an empirically derived background air pollution model, and a
      purposely designed time-activity-based exposure model (TOTEM). This paper
      describes the structure of the modeling system; presents results of field
      calibration, validation, and sensitivity analysis; and illustrates the use of the
      model to analyze journey-time exposures of schoolchildren.

PMID- 15476730
TI  - Cd and Zn in atmospheric deposit, soil, wheat, and milk.
AB  - Continuous air quality monitoring in the Vojvodina district of Serbia and
      Montenegro has shown high levels of Cd, especially in the outskirts of large
      towns such as Kikinda. The construction and metal processing industries located
      in Kikinda have been emitting significant amounts of heavy metals into the
      environment. The levels of Cd and Zn were monitored in the region of Kikinda and
      compared to their concentrations detected in Novi Sad, the capital of Vojovodina,
      where emission of heavy metals originated mostly from vehicle traffic. The study
      was performed during the economic sanctions when industrial production decreased
      drastically. The consequence of that was a significant decrease of the
      concentration of Cd and Zn in atmospheric deposits. Data collected during 3 years
      indicated a direct influence of atmospheric deposits on heavy metal distribution
      in the chain soil-cattle feed-milk. Decreased Cd concentrations of 93% in
      atmospheric deposits in the Kikinda region resulted in decreased Cd
      concentrations of 17% in cattle feeds and 13% in milk. Decreased Zn
      concentrations of 58% in atmospheric deposits caused reduced Zn concentrations of
      30% in soil, 17% in cattle feeds, and 17% in milk.

PMID- 15476731
TI  - Can we use fixed ambient air monitors to estimate population long-term exposure
      to air pollutants? The case of spatial variability in the Genotox ER study.
AB  - Associations between average total personal exposures to PM2.5, PM10, and NO2 and
      concomitant outdoor concentrations were assessed within the framework of the
      Genotox ER study. It was carried out in four French metropolitan areas (Grenoble,
      Paris, Rouen, and Strasbourg) with the participation, in each site, of 60-90
      nonsmoking volunteers composed of two groups of equal size (adults and children)
      who carried the personal Harvard Chempass multipollutant sampler during 48 h
      along two different seasons ("hot" and "cold"). In each center, volunteers were
      selected so as to live (home and work/school) in three different urban sectors
      contrasted in terms of air pollution (one highly exposed to traffic emissions,
      one influenced by local industrial sources, and a background urban environment).
      In parallel to personal exposure measurements, a fixed ambient air monitoring
      station surveyed the same pollutants in each local sector. A linear regression
      model was accommodated where the dependent pollutant-specific variable was the
      difference, for each subject, between the average ambient air concentrations over
      48 h and the personal exposure over the same period. The explanatory variables
      were the metropolitan areas, the three urban sectors, season, and age group.
      While average exposures to particles were underestimated by outdoor monitors, in
      almost all cities, seasons, and age groups, differences were lower for NO2 and,
      in general, in the other direction. Relationships between average total personal
      exposures and ambient air levels varied across metropolitan areas and local urban
      sectors. These results suggest that using ambient air concentrations to assess
      average exposure of populations, in epidemiological studies of long-term effects
      or in a risk assessment setting, calls for some caution. Comparison of personal
      exposures to PM or NO2 with ambient air levels is inherently disturbed by indoor
      sources and activities patterns. Discrepancies between measurement devices and
      local and regional sources of pollution may also strongly influence how the
      ambient air concentrations relate to population exposure. Much attention should
      be given to the selection of the most appropriate monitoring sites according to
      the study objectives.

PMID- 15476732
TI  - Can 4-nonylphenol induce vitellogenin-like proteins in the clam Tapes
      philippinarum?
AB  - Vitellogenins (Vg) are precursors of egg-yolk proteins (vitellins) constituting
      energy reserves for embryos. In oviparous females, Vg are produced in the liver
      (or equivalent organs) under the control of endogenous estrogens, released into
      the bloodstream (plasma or hemolymph), and stored in developing oocytes. Although
      Vg levels are generally undetectable in male plasma, they may significantly
      increase in (xeno-)estrogen-exposed males. The aim of the present study was to
      evaluate estrogenic effects of 4-nonylphenol (NP) in sexually differentiated
      males and females of the Manila clam Tapes philippinarum. Clams were exposed for
      7 days to various sublethal NP concentrations (0, 0+acetone, 0.025, 0.05, 0.1,
      and 0.2 mg NP/L) and Vg-like protein levels were evaluated in both hemolymph and
      digestive glands of mollusks by the alkali-labile phosphate assay. This method,
      based on the determination of phosphates released by Vg, has previously been used
      to detect Vg concentrations in both fish plasma and bivalve hemolymph. Although
      Vg levels were generally higher in both hemolymph and digestive gland of T.
      philippinarum females, males appeared to be more sensitive than females to the
      estrogenic effects of NP. In males exposed to 0.1 and 0.2 mg NP/L, Vg levels
      increased significantly in both hemolymph (P < 0.05 and P < 0.01, respectively)
      and digestive gland (p < 0.05), whereas no changes were observed in those of
      females. Although the mechanisms by which NP exerts its in vivo endocrine
      modulating effects in bivalve mollusks remain unclear, the results of this study
      demonstrate that NP may induce Vg-like proteins in T. philippinarum, particularly
      males.

PMID- 15476733
TI  - The role of urban air pollutants on the performance of heavy metal accumulation
      in Usnea amblyoclada.
AB  - Lichens incorporate heavy metals according to a selectivity sequence; therefore,
      their uptake rate can be affected when elements with a high affinity for cell
      wall exchange sites or that provoke harmful alterations to the metabolism of
      lichen thalli are present in the environment. The aim of this study was to
      examine the effect of urban pollutants on the accumulation of some heavy metals
      in Usnea amblyoclada. Lichen samples were transplanted for 1 month to both a
      polluted and a nonpolluted area in Cordoba, Argentina. They were then collected
      and soaked in tridistilled water or in solutions containing different
      concentrations of Cu, Ni, Pb, and Zn salts. The uptake of Cu2+, Ni2+, Zn2+, and
      Pb2+, and other parameters indicative of lichen damage were measured in all the
      lichen samples. The thalli retrieved from the polluted area showed significant
      increases in both the malonaldehyde content and the electrical conductivity of
      the water in which they had been immersed. These results indicate that the
      atmospheric pollutants could be responsible for the significant damage to the
      lichen's cellular membranes, thus altering several mechanisms related to the
      uptake of heavy metals. Both the area of transplantation and the concentration of
      the metallic solutions had significant effects on the levels of Cu, Ni, and Pb
      measured in lichen thalli; however, no significant differences were observed in
      Zn concentrations. The highest uptakes corresponded to Pb and Cu, suggesting that
      they probably have a higher affinity with the lichen cell wall exchange sites.
      This study confirms the fact that, although lichens can be useful biological
      indicators, the physiological mechanisms involved in metal uptake should be
      carefully analyzed. Therefore, when estimating the heavy metal content of an
      environment, the competitive mechanism for cation uptake should be considered
      especially in areas where the presence of high levels of metals with a strong
      binding affinity is suspected. The presence of secondary products in the lichens
      could be responsible for the selective uptake of cations and for a possible
      tolerance to their presence.

PMID- 15476734
TI  - Brief exposures to NO2 augment the allergic inflammation in asthmatics.
AB  - Exposure to high ambient levels of nitrogen dioxide (NO2) enhances the airway
      reaction in humans to allergen, measured as decreased pulmonary function. We
      tested whether this NO2 effect is associated with an increased inflammatory
      response to allergen in the airways. To mimic real-life conditions, in which
      exposure to high ambient levels of NO2 occurs only during short periods of time
      but often several times a day, we used a repeated-exposure model. On day 1, 18
      subjects with allergic asthma were exposed, in randomized order, to purified air
      or to 500 microg/m3 NO2 for 15 min, and on day 2 for 2 x 15 min. Allergen was
      inhaled 3-4h after the NO2 exposures on both days. Symptoms, pulmonary function,
      and inflammatory response in sputum and blood were measured daily. Eosinophil
      cationic protein in both sputum and blood increased more from day 1 to day 3
      after NO2+allergen than after air+allergen, whereas eosinophil counts did not
      differ. The change in myeloperoxidase was significantly greater after
      NO2+allergen than after air+allergen in blood but not in sputum. This finding was
      not accompanied by raised levels of neutrophils in sputum and blood. Symptoms and
      pulmonary function were equally affected by NO2+allergen and air+allergen. We
      conclude that two to three brief exposures to ambient levels of NO2 can prime
      circulating eosinophils and enhance the eosinophilic activity in sputum in
      response to inhaled allergen. This might be an important mechanism by which air
      pollutants amplify the inflammatory reactions in the airways.

PMID- 15476735
TI  - Multiple metal accumulation as a factor in learning achievement within various
      New Orleans elementary school communities.
AB  - In New Orleans, the elementary school system is divided into attendance districts
      with established boundaries that define student enrollment among schools. This
      study concerns environmental quality as defined by amount of soil metals (Pb, Zn,
      Cd, Ni, Mn, Cu, Co, Cr, and V) in attendance district elementary school
      communities (n = 111) paired with learning achievement as measured by individual
      test scores (n = 32,741) of students enrolled at each school. The Louisiana
      Educational Assessment Program (LEAP) 4th grade scores measure learning
      achievement for English language arts, social studies, mathematics, and science.
      The best fit between environmental quality and higher learning achievement is
      found to be inversely associated with the sum of the metals or multiple metal
      accumulations (MMA) in New Orleans communities. The P values for MMA partitions
      for ELA, SOC, MAT, and SCI are 0.57 x 10(-7), 0.29 x 10(-8), 0.41 x 10(-6), and
      0.17 x 10(-8), respectively. Efforts to prevent childhood metal exposure should
      improve New Orleanians' learning achievement as measured by the LEAP scores and
      thereby enhance the socioeconomic situation in contaminated communities. This
      study establishes global relationships between LEAP scores in schools and soil
      metal concentrations in school neighborhoods. However, these data do not allow
      relating of the LEAP scores with metal levels for individual students.

PMID- 15476736
TI  - A questionnaire for assessing environmental tobacco smoke exposure.
AB  - Exposure to environmental tobacco smoke (ETS) has been associated with adverse
      health consequences. In this study, the association between self-reported ETS
      exposure and serum cotinine levels was examined. As part of the population-based
      Epidemiology of Hearing Loss Study in Beaver Dam, WI, self-reported data on ETS
      were obtained at the 5-year follow-up examination (1998-2000; n = 2800). Serum
      cotinine levels were obtained on 643 of these participants (53-75 years old).
      Serum cotinine levels increased with reported number of hours of recent ETS
      exposure. Most (95.3%) participants who reported being smokers had serum cotinine
      levels >15 ng/mL, compared with only 2.7% of nonsmokers. Usual ETS exposure among
      nonsmokers was assessed with a brief questionnaire quantifying exposure at work,
      at home, and in social settings, and then classified into three levels of
      exposure. Those reporting little or no exposure had a geometric mean cotinine
      level of 0.06 ng/mL (95% confidence interval (CI): 0.05, 0.07), compared with
      0.14 (95% CI: 0.09, 0.22) and 0.63 (95% CI: 0.36, 1.10) for those reporting
      moderate and high ETS exposure, respectively (F-test for trend: P < 0.001). These
      results suggest that the questionnaire can be used to distinguish relative levels
      of exposure to ETS.

PMID- 15476737
TI  - Environmental exposure to cadmium at a level insufficient to induce renal tubular
      dysfunction does not affect bone density among female Japanese farmers.
AB  - Some recent research suggests that environmental exposure to cadmium, even at low
      levels, may increase the risk of osteoporosis, and that the bone demineralization
      is not just a secondary effect of renal dysfunction induced by high doses of
      cadmium as previously reported. To investigate the effect of exposure to cadmium
      at a level insufficient to induce kidney damage on bone mineral density (BMD) and
      bone metabolism, we conducted health examinations on 1380 female farmers from
      five districts in Japan who consumed rice contaminated by low-to-moderate levels
      of cadmium. We collected peripheral blood and urine samples and medical and
      nutritional information, and measured forearm BMD. Analysis of the data for
      subjects grouped by urinary cadmium level and age-related menstrual status
      suggested that cadmium accelerates both the increase of urinary calcium excretion
      around the time of menopause and the subsequent decrease in bone density after
      menopause. However, multivariate analyses showed no significant contribution of
      cadmium to bone density or urinary calcium excretion, indicating that the results
      mentioned above were confounded by other factors. These results indicate that
      environmental exposure to cadmium at levels insufficient to induce renal
      dysfunction does not increase the risk of osteoporosis, strongly supporting the
      established explanation for bone injury induced by cadmium as a secondary effect.

PMID- 15476738
TI  - Blood manganese concentrations among first-grade schoolchildren in two South
      African cities.
AB  - Little information exists on the environmental exposures to low levels of
      organometallic manganese (a principal combustion product from manganese
      containing fuel additives) and public health. This study was undertaken to
      establish biological and environmental levels of manganese among first-grade
      schoolchildren in the South African cities of Johannesburg and Cape Town. The
      study was undertaken subsequent to partial introduction of the manganese
      containing fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT) to
      South African petrol in the Johannesburg region only, about 24 months prior to
      the commencement of the study, and in anticipation of possible future increases
      in MMT use in the rest of the country. This study involved the measurement of
      manganese concentrations in the blood of the total number of 814 of grade one
      schoolchildren (430 and 384 in Cape Town and Johannesburg, respectively), and in
      water supplies, soil, and classroom dust at a total number of 21 participating
      schools. The results indicated higher concentrations of manganese in school soil
      (P=0.0007) and dust (P=0.0071) samples from Johannesburg relative to Cape Town.
      Similarly, the mean blood manganese concentration in Johannesburg study subjects
      (9.80 microg/L, SD 3.59) was significantly higher than that in Cape Town study
      subjects (6.74 microg/L, SD 3.47), after allowing for the clustering effect
      within schools and adjusting for the confounding effect of population group
      (P<0.0001). The blood manganese levels of 4.2% and 12.5% of children in Cape Town
      and Johannesburg, respectively, equaled or exceeded 14 microg/L, the upper normal
      reference value specified by the Agency for Toxic Substances Disease Registry
      (ATSDR, 2000). Importantly, levels of manganese in blood were found to be
      significantly associated with concentrations of manganese in classroom dust at
      schools.

PMID- 15476739
TI  - Exploring nonlinear association between prenatal methylmercury exposure from fish
      consumption and child development: evaluation of the Seychelles Child Development
      Study nine-year data using semiparametric additive models.
AB  - Studies of the association between prenatal methylmercury exposure from maternal
      fish consumption and neurodevelopmental test scores in the Seychelles Child
      Development Study have not found adverse effects through age 9 years. The
      analysis for the most recent 9-year data (Lancet 361 (2003) 1686) employed
      conventional linear regression models. In this study we reanalyzed the same
      Seychelles 9-year data using semiparametric additive models with different
      degrees of smoothing to explore whether nonlinear effects of prenatal exposure
      were present. Of 21 endpoints in the linear analysis, we chose only those with a
      two-tailed P value less than 0.2 for the effect of prenatal exposure. Six
      endpoints met the criterion. A nonlinear effect was identified with the more
      smooth model for only one endpoint. The test for an overall effect of prenatal
      exposure was also significant, with a P value of 0.04, while the corresponding P
      value in the linear regression analysis was 0.08. The nonlinear curve appeared to
      be nearly flat when the level was below approximately 12 ppm in maternal hair,
      with a linear trend above that level, suggesting a possible adverse effect in the
      uppermost range of prenatal exposure included in this cohort. Because of the
      descriptive nature of semiparametric additive models, the P values are not
      precise, and certainly there are fewer data above 12 ppm. We conclude that this
      reanalysis supports the primary linear analysis, showing little evidence for a
      prenatal adverse effect.

PMID- 15476740
TI  - The use and disposal of household pesticides.
AB  - Most pesticides are synthetic chemicals manufactured specifically for their toxic
      properties to the target species, and widely used globally. Several
      epidemiological studies in the United States have suggested health concerns
      arising from the chronic exposure of young children to pesticides in the domestic
      environment. In the UK very little is currently known about how nonoccupational
      pesticides are being used or disposed of. Any use of pesticides is a potential
      risk factor for children's exposure, and any potential exposure is likely to be
      reduced by the parents' adopting precautionary behaviour when using these
      pesticide products. This was investigated using a sample of 147 parents from the
      Avon Longitudinal Study of Parents and Children cohort in and around Bristol,
      through an in-depth interview between August and November 2001. The results of
      this study add to the understanding of the underlying behaviour of parents
      applying pesticide products in the home environment in the UK. Pesticides are
      readily available, and are normally purchased in do-it-yourself shops and
      supermarkets and mostly disposed of in domestic waste. Safety was stated by 45%
      of parents to be the most important factor to consider when buying a pesticide.
      When buying pesticide products, labels were stated to be the most important
      source of information about pesticides. However, a third of parents stated they
      would not follow the product label exactly when using a product, just under half
      felt labels were both inadequate and hard to understand, and about 10% of parents
      would not take notice of warnings on the pesticide label. Less than half of
      parents would use gloves when applying a pesticide, although the use of
      protective equipment such as gloves during the application of pesticides could
      greatly reduce the exposure. It is a public health concern that the instructions
      on the labels of products may not always be understood or followed, and further
      understanding of user behaviour is needed.

PMID- 15476741
TI  - Characterization of NOM in the Han River and evaluation of treatability using UF
      NF membrane.
AB  - Chlorine reacts with the natural organic matter (NOM) that remains in waters and
      forms halogenated by-products. Some of these products such as trihalomethanes
      (THMs) and haloacetic acids (HAAs) have been known to cause cancer and other
      toxic effects to human beings. Disinfection is a process for the inactivation of
      pathogenic microorganisms and prevention of waterborne diseases. Despite these
      advantages, disinfection needs to be evaluated and is of concern because of the
      serious risks to human health. Therefore, this study characterized NOM, which is
      a disinfection by-product (DBP) precursor, in the water treatment processes from
      the Han River and evaluated the removal efficiencies of NOM fractions by
      conventional and advanced processes. The raw water from the Han River contained
      higher hydrophilic fraction than the hydrophobic fraction. The hydrophilic NOM
      constituted still 55-70% of NOM in waters after each process. Since the
      hydrophilic NOM exhibited higher HAAFP than hydrophobic NOM, chlorination of the
      Han River water produced higher haloacetic acid formation potential (HAAFP) than
      trihalomethane formation potential (THMFP). When the fractions of DBPFP are
      expressed as percentage of total organic halide formation potential (TOXFP),
      THMFP, HAAFP, and others are 26%, 43%, and 31% of the TOXFP, respectively. UF
      membrane could replace conventional processes showing a little higher removal
      efficiency of NOM and DBPFP, but advanced processes will be required to meet
      future requirements. The ultrafiltration (UF)-nanofiltration (NF) combined
      membrane process had better removal efficiency of NOM compared to other
      processes. Therefore, the results of this study suggest that the UF-NF membrane
      process is one of the best available ways for removing NOM.

PMID- 15476742
TI  - Absence of clinically important HERG channel blockade by three compounds that
      inhibit phosphodiesterase 5--sildenafil, tadalafil, and vardenafil.
AB  - Compounds that inhibit phosphodiesterase 5 (PDE5) have been developed for the
      treatment of erectile dysfunction. Because men with erectile dysfunction
      frequently have comorbid cardiovascular disease, they may have limited cardiac
      repolarization reserve and be at risk of arrhythmia if treated with medications
      that prolong ventricular repolarization. The human ether-a-go-go related gene
      (HERG) channel is important for repolarization in human myocardium and is a
      common target for drugs that prolong the QT interval. We studied the ability of
      three compounds that inhibit PDE5--sildenafil, tadalafil, and vardenafil--to
      block the HERG channel. Using a whole cell variant of the patch-clamp method, the
      HERG current was measured in a stably transfected human embryonic kidney cell
      line expressing the HERG channel. The compounds produced dose-dependent
      reductions in HERG current amplitude over a concentration range of 0.1 to 100
      microM. The IC50 values were 12.8 microM for vardenafil and 33.3 microM for
      sildenafil. Because the maximum soluble concentration of tadalafil (100 microM)
      produced only a 50.9% inhibition of the HERG current amplitude, the IC50 value
      for tadalafil could not be determined with the Hill equation. Tadalafil had the
      weakest capacity to block the HERG channel, producing a 50.9% blockade at the
      maximum soluble concentration (100 microM), compared with 86.2% for vardenafil
      (100 microM) and 75.2% for sildenafil (100 microM). In conclusion, the
      concentrations of the PDE5 inhibitors required to evoke a 50% inhibition of the
      HERG current were well above reported therapeutic plasma concentrations of free
      and total compound. None of the three compounds was a potent blocker of the HERG
      channel.

PMID- 15476743
TI  - Extracellular signal-regulated kinase activation and Bcl-2 downregulation mediate
      apoptosis after gemcitabine treatment partly via a p53-independent pathway.
AB  - Gemcitabine is a promising compound for the treatment of human lung cancer.
      Although apoptosis has been shown to play a role in certain cell types with
      gemcitabine, the steps leading to cell death after the drug-target interaction
      are not well understood. We studied the molecular mechanisms of gemcitabine
      induced apoptosis and determined the role of p53 function on the cytotoxic
      effects of gemcitabine in human nonsmall cell lung cancer (NSCLC) H1299 and
      H1299/p53 cells. Here, we found that gemcitabine induced an apoptotic cell death
      via a Bcl-2-dependent caspase-9 activation pathway. Moreover, phosphorylated
      activation of extracellular signal-regulated kinase (ERK) was observed upon
      gemcitabine treatment. Genetical or pharmacological inhibition of ERK activation
      markedly blocked gemcitabine-induced cell death. Furthermore, inactivation of Akt
      was also involved in this event. Taken together, our observations indicate that
      ERK activation and Akt inactivation mediated gemcitabine-induced apoptosis
      independently of p53 in human NSCLC H1299 cells.

PMID- 15476744
TI  - Hexadecylphosphocholine causes rapid cell death in canine mammary tumour cells.
AB  - Hexadecylphosphocholine (HePC, Miltefosine) is an antitumour phospholipid and
      known inducer of apoptosis in human breast cancer cells. The mechanism underlying
      the induction of cell death by HePC, however, is not clear yet. In this study, we
      have investigated the cytotoxic effects of HePC on canine mammary tumour cells
      (CMTs) in vitro. Upon addition of HePC, CMTs rapidly exhibited several features
      that resembled apoptotic cell death. Cells showed externalization of
      phosphatidylserine, a hallmark of apoptosis, within 5 min after addition of HePC
      at concentrations as low as 10 microM. Furthermore, rapid swelling of
      mitochondria was observed. Rounding and detachment of cells followed within 30
      min. However, fragmentation of nuclear DNA could not be observed. Overall, HePC
      was shown to induce a type of cell death in CMTs that in some aspects resembles
      apoptosis, though the process proceeds much more rapidly than reported for other
      tumour cell lines.

PMID- 15476745
TI  - Selective effects of quercetin on the cell growth and antioxidant defense system
      in normal versus transformed mouse hepatic cell lines.
AB  - Quercetin is a dietary anticancer chemical that is capable of inducing apoptosis
      in tumor cells. However, little is known about its biological effect on
      nonmalignant cells, although the effect is one of the critical criteria to
      evaluate the clinical efficacy of the anticancer agent. In this study, we
      investigated the effects of quercetin on cell growth and apoptosis using
      embryonic normal hepatic cell line (BNL CL.2) and its SV40-transformed cell line
      (BNL SV A.8). We also evaluated the effects of quercetin on the antioxidant
      defense system in those cells. BNL SV A.8 cells were more sensitive to quercetin
      mediated cytotoxicity than BNL CL.2 cells. In addition, the enzyme assays showed
      that quercetin actively stimulated the antioxidant defense systems including
      superoxide dismutase, catalase, glutathione, and glutathione reductase only in
      the BNL CL.2 cells. In particular, quercetin significantly reduced superoxide
      dismutase activity and increased the malonaldehyde content in BNL SV A.8 cells.
      These are thought to be closely related to quercetin-mediated apoptosis. Our
      findings suggest that quercetin is a dietary flavonoid that is capable of
      inducing selective growth inhibition and apoptosis in hepatic tumor cells, but
      not in normal cells.

PMID- 15476746
TI  - Roles of serotonin receptor subtypes for the antinociception of 5-HT in the
      spinal cord of rats.
AB  - The contribution of 5-HT (5-hydroxytryptamine) receptor subtypes to the
      antinociception produced by intrathecal 5-HT in the formalin test was
      investigated in rats. Intrathecal 5-HT suppressed both phases of behaviors
      produced by 5% formalin, and this was blocked by antagonists for 5-HT(1B) (3-[3
      (Dimethylamino)propyl]-4-hy-droxy-N-[4-(4-pyridinyl)phenyl]benzamide
      dihydrochloride, GR 55562), 5-HT(2C) (N-ormethylclozapine/8-Chloro-11-(1
      piperazinyl)-5H-dibenzo[b,e][1,4]diazepine, D-MC), 5-HT3 (1-Methyl-N-(8-methyl-8
      azabicyclo[3.2.1]-oct-3-yl)-1H-indazole-3-carboxamide maleate, LY-278,584) and 5
      HT4 receptors (4-Amino-5-chloro-2-metho-xy-benzoic acid 2-(diethylamino)ethyl
      ester hydrochloride, SDZ-205,557), but not the 5-HT(1D) receptor antagonist 3-[4
      (4-Chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanol hydrochloride (BRL
      15572). The 5-HT(1A) receptor antagonist N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]
      N-2-pyridinyl-cyclohexanecarboxamide maleate (WAY-100635) decreased only the
      second phase antinociception of 5-HT. Intrathecal administration of agonists for
      5-HT(1A) (3-(N,N-Dipropylaminoethyl)-1H-indole-5-carboxamide maleate, Dipropyl
      5CT), 5-HT(1B) (7-Trifluoromethyl-4(4-met-hyl-1-piperazinyl)-pyrrolo[1,2
      a]quinoxaline maleate, CGS-12066A), 5-HT(2C) (6-Ch-loro-2-(1-piperazinyl)pyrazine
      hydrochloride, MK 212), 5-HT3 (N-(3-Chlorophenyl)imidodicarbonimidic diamide
      hydrochloride, m-CPBG) and 5-HT4 receptors (2-[1-(4
      Piperonyl)piperazinyl]benzothiazole, BZTZ) suppressed both phases of the formalin
      response. The results of the present study indicate that spinal 5-HT(1B,) 5
      HT(2C,) 5-HT3 and 5-HT4 receptors, but not the 5-HT(1D) receptor, mediate
      antinociception produced by 5-HT in the formalin test. The relevance of the 5
      HT(1A) receptor is less clear because of the different effects of antagonist and
      agonist.

PMID- 15476747
TI  - Increased 5-HT2A receptor expression and function following central
      glucocorticoid receptor knockdown in vivo.
AB  - Central glucocorticoid receptor function may be reduced in depression. In vivo
      modelling of glucocorticoid receptor underfunctionality would assist in
      understanding its role in depressive illness. The role of glucocorticoid
      receptors in modulating 5-HT(2A) receptor expression and function in the central
      nervous system (CNS) is presently unclear, but 5-HT(2A) receptor function also
      appears altered in depression. With the aid of RNAse H accessibility mapping, we
      have developed a 21-mer antisense oligodeoxynucleotide (5'-TAAAAACAGGCTTCTGATCCT
      3', termed GRAS-5) that showed 56% reduction in glucocorticoid receptor mRNA and
      80% down-regulation in glucocorticoid receptor protein in rat C6 glioma cells.
      Sustained delivery to rat cerebral ventricles in slow release biodegradable
      polymer microspheres produced a marked decrease in glucocorticoid receptor mRNA
      and protein in hypothalamus (by 39% and 80%, respectively) and frontal cortex (by
      26% and 67%, respectively) 5 days after a single injection, with parallel
      significant up-regulation of 5-HT(2A) receptor mRNA expression (13%) and binding
      (21%) in frontal cortex. 5-HT(2A) receptor function, determined by DOI-head
      shakes, showed a 55% increase. These findings suggest that central 5-HT(2A)
      receptors are, directly or indirectly, under tonic inhibitory control by
      glucocorticoid receptor.

PMID- 15476748
TI  - Differential regulation of cocaine-induced locomotor activity in inbred long
      sleep and short-sleep mice by dopamine and serotonin systems.
AB  - Acute injection of cocaine increases locomotor activity of inbred long-sleep
      (ILS) mice to a greater extent than inbred short-sleep (ISS) mice. Strain
      differences in dopamine and/or serotonin (5-HT) neurotransmission could underlie
      these behavioral differences. Here, we found that dopamine D1, 5-HT(2A) and 5-HT3
      receptor antagonists reduced cocaine-stimulated activity selectively in ILS mice.
      In contrast, 5-HT transporter (SERT) or 5-HT(1A) receptor antagonists potentiated
      cocaine-stimulated activity in ISS, but not in ILS, mice; this potentiation in
      ISS mice was abolished by dopamine D1 receptor blockade. Thus, in ILS mice,
      cocaine-induced activation of D1, 5-HT(2A) or 5-HT3 receptors is sufficient to
      produce locomotor stimulation. In contrast, ISS mice require pharmacologically
      increased 5-HT levels, which appear to result in increased dopamine
      neurotransmission, for cocaine-induced activation. Our results demonstrate strain
      differences in dopamine/5-HT receptor subtypes and their interactions that
      contribute to the differential behavioral responsiveness of ILS and ISS mice to
      cocaine.

PMID- 15476749
TI  - Kappa opioid agonists suppress chloroquine-induced scratching in mice.
AB  - Chemotherapy of malaria fever with chloroquine is often associated with
      generalized pruritus of unknown pathogenesis. This adverse side effect leads to
      diminished compliance. We report that chloroquine (1.25-40 mg/kg, s.c.) elicits
      dose-related, compulsive, and vigorous scratching in mice. This frenzied behavior
      is essentially abolished when the mice are pretreated s.c. or orally with
      nalfurafine (TRK-820), a centrally penetrating kappa opioid agonist. Peripheral
      kappa receptors are involved because chloroquine-induced scratching is also
      antagonized by the peripherally restricted kappa agonist, ICI 204,448: R,S-N-[2
      (N-methyl-3,4-dichlorophenylacetamido)-2-(3-carboxyphenyl) ethyl]pyrrolidine. We
      propose that combination therapy for malaria with chloroquine and a kappa agonist
      (probably one targeting peripheral receptors) will lead to better treatment
      compliance because of a reduced incidence of pruritus.

PMID- 15476750
TI  - 5-HT7, but not 5-HT2B, receptors mediate hypotension in vagosympathectomized
      rats.
AB  - This study evaluated the possible involvement of 5-HT(2B) receptors in long
      lasting hypotension to 5-hydroxytryptamine (5-HT), which is predominantly
      mediated by 5-HT7 receptors, in anaesthetised vagosympathectomized rats.
      Intravenous injections of 5-HT and 5-carboxamidotryptamine (5-CT) elicited a dose
      dependent hypotension that was dose-dependently antagonised by (R)-1-[(3
      hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl) ethyl] pyrrolidine (SB
      269970; a selective 5-HT7 receptor antagonist), but not by saline. Interestingly,
      alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine (BW723C86; a 5-HT(2B)
      receptor agonist) produced vasopressor responses without affecting hypotension to
      5-HT. These results suggest that hypotension to 5-HT and 5-CT is mainly mediated
      by 5-HT7 receptors, whilst the role of 5-HT(2B) receptors seems unlikely.

PMID- 15476751
TI  - Unique roles of G protein-coupled histamine H2 and gastrin receptors in growth
      and differentiation of gastric mucosa.
AB  - Disruption of histamine H2 receptor and gastrin receptor had different effects
      growth of gastric mucosa: hypertrophy and atrophy, respectively. To clarify the
      roles of gastrin and histamine H2 receptors in gastric mucosa, mice deficient in
      both (double-null mice) were generated and analyzed. Double-null mice exhibited
      atrophy of gastric mucosae, marked hypergastrinemia and higher gastric pH than
      gastrin receptor-null mice, which were unresponsive even to carbachol. Comparison
      of gastric mucosae from 10-week-old wild-type, histamine H2 receptor-null,
      gastrin receptor-null and double-null mice revealed unique roles of these
      receptors in gastric mucosal homeostasis. While small parietal cells and
      increases in the number and mucin contents of mucous neck cells were secondary to
      impaired acid production, the histamine H2 receptor was responsible for chief
      cell maturation in terms of pepsinogen expression and type III mucin. In double
      null and gastrin receptor-null mice, despite gastric mucosal atrophy, surface
      mucous cells were significantly increased, in contrast to gastrin-null mice.
      Thus, it is conceivable that gastrin-gene product(s) other than gastrin-17, in
      the stimulated state, may exert proliferative actions on surface mucous cells
      independently of the histamine H2 receptor. These findings provide evidence that
      different G-protein coupled-receptors affect differentiation into different cell
      lineages derived from common stem cells in gastric mucosa.

PMID- 15476752
TI  - Effect of a plant histaminase on asthmalike reaction induced by inhaled antigen
      in sensitized guinea pig.
AB  - This study evaluates the effects of a copper amine oxidase (histaminase) purified
      from the pea seedling as a free or immobilized enzyme on asthmalike reactions to
      inhaled antigen in actively sensitized guinea pig in vivo. Male albino guinea
      pigs, sensitized with ovalbumin, were challenged with the antigen given by
      aerosol; free histaminase or CNBr-Sepharose immobilized histaminase was given
      intraperitoneally (20 microg, 3 or 24 h before antigen challenge) or by aerosol
      (4 microg, 30 min before or during ovalbumin aerosol). The following parameters
      were examined: latency time for the onset of respiratory abnormalities, cough
      severity score, and occurrence and duration of dyspnea. We also evaluated lung
      histopathology, mast cell degranulation, and lung myeloperoxidase and
      malonydialdehyde levels. Histaminase significantly reduced the severity of cough
      and the occurrence of dyspnea and delayed the onset of respiratory abnormalities.
      Both enzymes prevented bronchial constriction, pulmonary air space inflation,
      leukocyte infiltration (evaluated as myeloperoxidase activity), and
      lipoperoxidation of cell membranes (evaluated as malonyldialdehyde production).
      No relevant differences in pharmacological potency were noted between free or
      immobilized enzyme. This study provides evidence that histaminase counteracts
      acute allergic asthmalike reaction in actively sensitized guinea pigs, raising
      the possibility of new therapeutic strategies for allergic asthma in humans.

PMID- 15476753
TI  - Inhibitory effect of low-dose estrogen on neointimal formation after balloon
      injury of rat carotid artery.
AB  - The current regimens of hormone replacement therapy for postmenopausal women,
      estrogen combined with progestogen, have failed to show beneficial effects for
      the prevention of atherosclerotic disease. Although the relatively higher dose of
      estrogen contained in those regimens exerted adverse effects, there are few data
      examining a lower dose of estrogen in an atherosclerosis model. Therefore, we
      investigated experimentally whether lower doses of estrogen could inhibit
      neointimal formation after balloon injury of the rat carotid artery. Ten-week-old
      Wistar rats were subjected to ovariectomy or sham-operation (n=7). Four days
      after ovariectomy, rats were implanted with an osmotic mini-pump containing 17
      beta estradiol (0.2, 1, 2, 10 and 20 microg/kg/day; n=6, 4, 8, 6 and 5,
      respectively) or placebo (n=10). After 3 days of hormone therapy, balloon injury
      was performed in the left common carotid artery. Neointimal formation was
      histologically evaluated 2 weeks after injury. Cross-sectional intimal area and
      the ratio of intimal area to medial area were dose-dependently reduced by
      estrogen replacement compared with those in ovariectomized rats without estrogen
      replacement. The effects of estrogen replacement were identical to those of an
      angiotensin II type 1 receptor blocker, candesartan. Interestingly, the effect
      was significant even in rats receiving lower doses of estrogen, in which plasma
      estradiol concentrations were not increased and the hyperplastic response of the
      uterus was minimal. These results suggest the efficacy of low-dose estrogen
      therapy for the protection of atherosclerosis.

PMID- 15476754
TI  - Pronounced hypothermic synergy between systemic baclofen and NOS inhibitor.
AB  - Baclofen was administered to rats systemically (intraperitoneal, i.p.) by itself
      or with L-NAME. Baclofen (1-7.5 mg/kg, i.p.) evoked dose-dependent hypothermia. L
      NAME (50 mg/kg, i.p.) was ineffective. For combined administration, L-NAME
      increased the relative potency of baclofen (F=10.77, p<0.05), indicating
      multiplicative interaction and synergism. The present data reveal a surprising
      and significant interaction between nitric oxide synthase (NOS) and baclofen
      induced hypothermia.

PMID- 15476755
TI  - Maternal role transition experiences of women hospitalized with PROM: a
      phenomenological study.
AB  - This study investigated the subjective experiences of the maternal role
      transition during the first two weeks of hospitalization for premature rupture of
      the amniotic membranes (PROM). Thirteen pregnant couples participated in the
      study by completing interviews. Average gestation of the expectant mothers was 27
      weeks and the women were already experiencing fetal movement during the first two
      weeks of hospitalization for PROM. Lincoln and Cuba's trustworthiness criteria
      were employed to evaluate methodological rigor. Colaizzi's phenomenological
      approach was used to analyze the structure of the experience. Four themes
      emerged: pending loss, concern about the safety of the fetus, identification of
      maternal roles, and the process of maternal role-making. The results provide a
      scientific basis for empowering nurses to assist with maternal role transition in
      high-risk pregnancies in a more sensitive and effective manner.

PMID- 15476756
TI  - The impact of a stage-matched intervention to promote exercise behavior in
      participants with type 2 diabetes.
AB  - This study was designed to develop and evaluate a stage-matched intervention
      (SMI) in Korean participants with type 2 Diabetes. The SMI was based on main
      constructs derived from the Transtheoretical Model match to the individual's
      stages of readiness for exercise behavior. The SMI was developed according to the
      results of the content validity tested by an expert group (n = 9). A control
      group pre- and post-test design was used for evaluating the impact of the SMI:
      the intervention group (n = 22) participated in the SMI for 3 months, while the
      control group (n = 23) received usual educational advice. The intervention group,
      compared to the control group, showed significant improvements in stages of
      change for exercise behavior (p < 0.001), physical activity levels (p < 0.001),
      and reductions in FBS (p < 0.05) and HbA(1)c (p < 0.05). This study yielded
      evidence for the beneficial impact of the SMI in participants with type 2
      Diabetes.

PMID- 15476757
TI  - The effect of wool vs. cotton head covering and length of stay with the mother
      following delivery on infant temperature.
AB  - Rectal temperature of 126 term infants was measured on admission to the nursery
      following variable periods of stay with the mother in the delivery room. Fifty
      nine infants who wore woolen hats after delivery had higher rectal temperature
      than 67 infants whose head was covered by loosely applied cotton diapers (36.5+/
      0.5 degrees C vs. 36.3+/-0.5 degrees C, respectively; p=0.03). Among them there
      were fewer infants who were admitted with rectal temperature 36 degrees C (12 vs.
      26, respectively; p=0.03). In multiple regression analyses accounting for head
      covering with woolen hats, birth weight, gender, delivery room temperature and
      length of stay with the mother, only birth weight and head covering with woolen
      hats were significantly associated with rectal temperature at arrival in the
      nursery (p=0.002 and 0.03, respectively), and only head covering with cotton
      diapers was significantly associated with rectal temperature 36 degrees C
      (p=0.03). Our data imply that covering heads of term newborns with simple woolen
      hats may reduce or prevent heat loss following delivery, and that adequate
      warming of infants is achieved during prolonged stay with the mother.

PMID- 15476758
TI  - 'Being in the same boat': ethnographic insights into an adolescent cancer unit.
AB  - Cancer may be considered a particularly challenging diagnosis for adolescents.
      Treatment for adolescents in the United Kingdom may be provided in paediatric or
      adult settings or, more rarely, in specialist adolescent cancer units. An
      ethnographic approach was adopted to gather 'insiders' views of one such unit
      using in-depth interviews with patients, parents and professionals, as well as
      non-participant observation of key events. Two data themes 'cancer and the cancer
      unit' and 'changes over time' are discussed in this paper. Benefits of the unit
      included shared understandings and the manner in which the privations of
      adolescent cancer were contained and managed by those involved.

PMID- 15476759
TI  - The physical workload of nursing personnel: association with musculoskeletal
      discomfort.
AB  - Direct care-nursing personnel around the world report high numbers of work
      related musculoskeletal disorders. This cross-sectional study examined the
      association between the performance of high-risk patient-handling tasks and self
      reported musculoskeletal discomfort in 113 nursing staff members in a veterans'
      hospital within the United States. Sixty-two percent of subjects reported a 7-day
      prevalence of moderately severe musculoskeletal discomfort. There was a
      significant association between wrist and knee pain and the number of highest
      risk patient-handling tasks performed per hour interacting with the load lifted.
      On units where lifting devices are readily available, musculoskeletal risk may
      have shifted to the wrist and knee.

PMID- 15476760
TI  - Explanatory model of health in bereaved parents post-fetal/infant death.
AB  - In order to identify which features contribute to attenuating or intensifying the
      deleterious consequences of a perinatal loss such that some family systems endure
      and sometimes even thrive when faced with such a situational stressor, while
      other family units seem to deteriorate and disintegrate under similar
      circumstances, an explanatory model of health was tested. The purpose of this
      longitudinal study was to examine how the relationships between the elements in
      the model namely: resources both internal (hardiness) and external (marital and
      social supports), as well as appraisal of the situation, predicted the health of
      110 bereaved couples (husbands and wives).

PMID- 15476761
TI  - Hope and despair: the awakening of hope following acute spinal cord injury-an
      interpretative study.
AB  - The aim of this paper was to explore the patients' experiences of hope during the
      first months following acute spinal cord injury. This qualitative study has a
      descriptive and explorative design. Data were collected by personal interviews (N
      = 10) at a rehabilitation centre in Norway. A phenomenological-hermeneutic
      approach inspired by Ricoeur was used to extract the meaning content of the
      patients' experiences. The findings revealed one main interpretation; the
      awakening of hope, expressed by two themes: hope and despair, and uncertainty.
      Awakening hopes, even sometimes silent hopes, constituted a contextual background
      in the immediate aftermath of spinal cord injury.

PMID- 15476762
TI  - Rigor in cross-cultural nursing research.
AB  - With the increasing number of cross-cultural nursing studies, many scholars have
      suggested methods for conducting cross-cultural research. However, rigor in cross
      cultural research has rarely been addressed. In this paper, five evaluation
      criteria for rigor in cross-cultural nursing research are proposed based on a
      review of the literature related to cross-cultural research published from 1965
      to 2003. The proposed evaluation criteria include: (a) cultural relevance; (b)
      contextuality; (c) appropriateness; (d) mutual respect; and (e) flexibility. We
      advocate that these evaluation criteria be used to ensure rigor of cross-cultural
      nursing research, whether quantitative or qualitative work.

PMID- 15476763
TI  - The knowledge level and precautionary measures taken by older adults during the
      SARS outbreak in Hong Kong.
AB  - The study aims to examine the knowledge and the practice of the precautionary
      measures taken by older adults in Hong Kong against the outbreak of severe acute
      respiratory syndrome (SARS). Overall, more than half the participants responded
      correctly that droplet transmission is one of the main transmission routes of
      SARS. Those who received formal education demonstrated that they acquired greater
      knowledge of the sources and precautionary measures for SARS. The types of
      precautionary measures used and the factors affecting their behaviours were
      discussed. The results of the study could help the health-care professionals
      develop appropriate health promotion and disease prevention programmes for older
      adults.

PMID- 15476765
TI  - Changes in patterns of knowing the patient: the case of British district nurses.
AB  - British district or home nurses, have until recent years been hidden from the
      wider context of the British National Health Service. Policy changes in UK over
      the last two decades of the 20th century have increasingly focussed on Primary
      Care Services and district nurses (DNs) have seen substantial changes to their
      workload. This paper addresses the question of how the changes in the
      organisation of Primary Care Services affected some aspects of DNs' work. Thus,
      the focus of this paper is an examination of the relationship DNs had with
      patients through a period of turbulent change. Knowing the patient is a central
      element of nursing practice. Data are presented here form a multi-site
      ethnographic study of DNs' work undertaken in four purposively sampled study
      sites. Applying Carper's (1978) framework, the data presented here show that
      there has been a shifting emphasis in knowing the patient from aesthetic and
      personal knowing to knowing about and empirical knowing.

PMID- 15476764
TI  - Factors associated with sexually transmitted disease clinic attendance.
AB  - Most people in the United States who are infected with sexually transmitted
      diseases (STDs) do not attend STD clinics for treatment in spite of the low-cost
      efficacious treatment. We asked a clinic and a community sample about perceived
      benefits and problems of attending an STD clinic. Analyses yielded two treatment
      oriented and two socially oriented, factors, which were also expressed in
      qualitative interviews. Further analyses suggested that treatment-oriented
      factors were more strongly associated with clinic attendance than were social
      factors, although respondents were more positive about expected quality of
      treatment than they were about retaining confidentiality. We suggest that
      implications of the results favor integrating STD care with other health care.

PMID- 15476766
TI  - Safety in nursing social research.
AB  - BACKGROUND: Researcher safety is an important consideration in all areas of
      nursing social research. Risks to researchers' safety are multidimensional and
      manifest differently, contingent on the context of the research encounters. AIM:
      To review researcher safety issues in social research with special attention to
      nursing. REVIEW FOCUS: A small number of studies are used in this article, as
      examples, to demonstrate the range of researcher safety issues in nursing. Some
      preliminary suggestions to help ensure researcher safety are outlined:
      organisational culture, resources, a researcher safety lead, systems and
      procedures, education and training and insurance. CONCLUSIONS: There is a need to
      raise the profile of researcher safety issues in nursing for all involved,
      including researchers, students, funders and review committees. The article
      highlights the importance of nursing researchers writing reflexively about their
      safety. There is also a need for new nursing research to assess the nature and
      extent of safety issues. Taken together, these issues represent the starting
      point for establishing researcher safety guidelines and identifying good practice
      for the nursing research community.

PMID- 15476767
TI  - Heavy metal adsorption by humic umbrisols: selectivity sequences and competitive
      sorption kinetics.
AB  - This work examines sorption kinetics of Cd, Cr, Cu, Ni, Pb, and Zn adsorbed
      simultaneously by four humic umbrisols, as well as the influence of the soil
      components on the adsorption rate. Starting from the value of K(d), the metals
      most adsorbed by the soils are Cu, Cr, and Pb. The soils that adsorb the largest
      amounts of metals have also the highest organic matter, oxide, and clay content.
      In general, the most common selectivity sequence of adsorption is Pb > Cr > Cu >
      Cd approximately Ni approximately Zn. Sorption kinetics is rapid for Cr, Cu, and
      Pb in all the soils studied and competes favorably for the adsorption sites with
      Cd, Ni, and Zn. Various rate equations (zero-order, first-order, second-order,
      Elovich, and power function) were applied to the kinetic data to obtain the
      corresponding rate coefficients. A second-order reaction best represents the
      kinetic data for Cr in most of the soils.

PMID- 15476768
TI  - Effect of surfactants on the cementation of cadmium.
AB  - The cementation of cadmium ions (Cd(2+)) from aqueous solution onto zinc was
      studied in two batch reactors, a batch stirred reactor lined with a cylindrical
      zinc sheet and another that used a rotating zinc cylinder. The rate of cadmium
      removal was studied as a function of speed of rotation, initial cadmium
      concentration, and the addition of certain surfactants and their mixtures.
      Rotational speed and initial cadmium concentration affect the rate of cadmium
      cementation. It was found that sodium dodecyl sulfate (SDS) improves the rate of
      cadmium cementation, while Triton X-100 and cetyltrimethylammonium bromide (CTAB)
      inhibit it. Thermodynamic parameters were calculated and discussed. Visual
      observations showed that cadmium deposits on the zinc sheet are in the form of a
      powder, while cadmium deposits on the zinc cylinder, in the presence of SDS, give
      porous grains which increases the roughness of the surface, leading to an
      increase in the cementation rate. The lowest deposit porosity was observed in the
      presence of CTAB, which corresponds to the highest decrease obtained in the rate
      of cadmium cementation. The cementation process was successfully applied to
      recover Cd(2+) spiked into an industrial wastewater sample.

PMID- 15476769
TI  - Molecular properties of adsorbates that affect the growth kinetics of archerite
      (KDP).
AB  - We explore the molecular properties of adsorbates that dramatically affect growth
      kinetics and morphology of the [100] face of archerite, also known as potassium
      dihydrogen phosphate (KH(2)PO(4) or KDP). Aqueous complexes of Al(III), Fe(III),
      and Cr(III) are known to affect KDP growth, albeit the actual step-pinning
      complex(es) is unknown. Using in situ atomic force microscopy (AFM), we measured
      changes in the growth rates of the [100] face of KDP with supersaturation in the
      presence of trace amounts of [Co(NH(3))(6)](3+), [Fe(CN)(6)](3-), eta(1)
      [Co(NH(3))(5)HPO(4)](+), eta(2)-[Co(NH(3))(4)HPO(4)](+), eta(2)
      [Co(NH(3))(4)P(2)O(7)H(2)](+), and [Rh(H(2)PO(4))(2)(H(2)O)(4)](+). Unlike in
      experiments using trivalent-metals, these complexes do not change stoichiometry
      or structure on the timescale of step motion, so that the actual molecular
      interactions that affect growth can be studied. Step velocity and morphology on
      the [100] face are unaffected by outer-sphere coordination complexes of either
      charge. Surprisingly, inner-sphere phosphatoammine complexes do not affect growth
      rates regardless of how the phosphate group is coordinated to the metal. However,
      doping the growth solution with [Rh(H(2)PO(4))(2)(H(2)O)(4)](+) results in
      profound step pinning, matching the behavior of KDP surfaces grown in the
      presence of Rh(III) after an equilibration period. Not only is an inner-sphere
      phosphate group needed to dock a trivalent metal to the step edge, but compatible
      hydrogen bonding of the remainder of the inner-sphere ligands with the bulk
      lattice is also essential.

PMID- 15476770
TI  - Effects of exchanged surfactant cations on the pore structure and adsorption
      characteristics of montmorillonite.
AB  - Ca-montmorillonite (Ca-Mont) was exchanged with two quaternary amines,
      tetramethylammonium (TMA) chloride and hexadecyltrimethylammonium (HDTMA)
      bromide, to study the surfactant ion exchange effect on the pore structure,
      surface characteristics, and adsorption properties of montmorillonite. The
      revolution of both the surface area and pore structure of montmorillonite was
      characterized based on classical and fractal analyses of the nitrogen isotherms
      as well as the XRD patterns. The change of surface characteristics was identified
      from FTIR patterns and zeta-potential plots. The adsorption isotherms of acid
      dye, Amido Naphthol Red G (AR1), were then measured to identify the effects of
      the ion-exchange process on the adsorption properties of montmorillonite. It was
      found that the exchange processes might induce an increase or decrease in the
      surface area, pore size, pore volume, and surface fractal dimension D of
      montmorillonite, depending on the size, the molecular arrangement, and the degree
      of hydration of the exchanged ion in the clay. On the other hand, it was also
      found that the hydrophobic bonding by conglomeration of large C(16) alkyl groups
      associated with HDTMA could cause positive charge development on the surface of
      montmorillonite, which was not observed for TMA-modified montmorillonite (TMM).
      The effects of the alteration of the surface characteristics of montmorillonites
      on their adsorption selectivity for acid dye were discussed.

PMID- 15476771
TI  - Adsorption and desorption of humic acid on aminated polyacrylonitrile fibers.
AB  - Aminated polyacrylonitrile fibers (APANFs) were prepared by surface modification
      and were used as an adsorbent to remove humic acid from aqueous solutions. The
      APANFs were found to be very effective in removing humic acid at the pH range
      from 2 to 10. The adsorption isotherm obeyed both the Langmuir and Freundlich
      models, and the adsorption kinetics followed an initial diffusion-controlled and
      then an attachment-controlled adsorption pattern. X-ray photoelectron
      spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy revealed
      that chemical bonds were formed between the nitrogen atoms in the amine groups on
      the fibers and humic acid molecules adsorbed, suggesting that, besides
      electrostatic interaction, surface complexation also played an important role in
      humic acid adsorption on the APANFs. The humic acid adsorbed on the APANFs can be
      effectively desorbed in a 0.1 M NaOH solution, and the regenerated APANFs can be
      reused in the subsequent adsorption cycles without significant loss of the
      adsorption capacities.

PMID- 15476772
TI  - Adsorption of Acid Blue 193 from aqueous solutions onto Na-bentonite and DTMA
      bentonite.
AB  - Dodecyltrimethylammonium bromide-modified bentonite (DTMA-bentonite) was prepared
      and tested as an adsorbent for an acid dye (Acid Blue 193, AB193) removal from
      aqueous solution in comparison with Na-bentonite. The effect of various
      experimental parameters was investigated using a batch adsorption technique. In
      this manner, the adsorption isotherms, adsorption kinetics, and temperature and
      pH effects upon Acid Blue 193 adsorption on Na-bentonite and DTMA-bentonite were
      thoroughly examined. Results show that a pH value of 1.5 is favorable for the
      adsorption of Acid Blue 193. The isothermal data could be well described by the
      Freundlich equation. The dynamical data fit well with the pseudo-second-order
      kinetic model. The adsorption capacity of DTMA-bentonite (740.5 mg g(-1)) was
      found to be around 11 times higher than that of Na-bentonite (67.1 mg g(-1)) at
      20 degrees C. Thermodynamic parameters such as activation energy (E(a)) and
      change in the free energy (DeltaG(0)), the enthalpy (DeltaH(0)), and the entropy
      (DeltaS(0)) were also evaluated. The overall adsorption process was exothermic
      but it is only spontaneous at 20 degrees C. The results indicate that Na
      bentonite and DTMA-bentonite could be employed as low-cost alternatives to
      activated carbon in wastewater treatment for the removal of color which comes
      from textile dyes.

PMID- 15476773
TI  - The adsorption of palmytic acid on rice husk ash chemically modified with Al(III)
      ion using the sol-gel technique.
AB  - Silica-incorporated aluminum (RHA-Al) was synthesized from rice husk ash (RHA)
      using the sol-gel technique. RHA-Al was calcined at 500 degrees C for 5 h to
      yield RHA-Al(C). The ratio of silica to alumina was found to be 4:1. The BET
      analysis of RHA-Al(C) showed an increase in total pore volume and specific
      surface area compared to RHA-Al. SEM and XRD showed that RHA-Al and RHA-Al(C)
      were composed of microcrystals and the surface of both samples had a porous
      structure. Adsorption studies of palmytic acid on RHA-Al and RHA-Al(C) at 30, 40,
      and 50 degrees C conformed to the Langmuir isotherm. The equilibrium parameter,
      R, revealed that both are good adsorbents for palmytic acid. The Gibbs free
      energy of adsorption, DeltaG(ads)(0), was determined to be between -21.0 and 
      26.0 kJ mol(-1). DeltaH(ads)(0) and DeltaS(ads)(0) for RHA-Al were found to be
      26.2 kJ mol(-1) and 158 J mol(-1), respectively. Corresponding values for RHA
      Al(C) were 31.7 kJ mol(-1) and 178 J mol(-1). The adsorption of fatty acid on RHA
      Al and RHA-Al(C) was an endothermic process, which occurred spontaneously. An
      FTIR study on the adsorbed material was used to determine the possible adsorbed
      complex on the surface of the adsorbent.

PMID- 15476774
TI  - Dynamic arsenic removal on a MnO2-loaded resin.
AB  - Previous batch studies on a polystyrene matrix loaded with manganese dioxide,
      synthesized from an anionic commercial resin in chloride form, have proven the
      efficiency of this sorbent in As(V) and As(III) removal. This solid is now tested
      with column experiments to predict its behavior in a treatment process. An
      artificial water, with a composition in major ions similar to that of granitic
      water, often contaminated with arsenic, was prepared. This artificial water was
      used to simulate arsenic removal processes under near-natural conditions and with
      a stable composition. Furthermore, the hydride generation AAS analytical method
      was optimized to measure low arsenic concentrations (1 to 20 microg/L).

PMID- 15476775
TI  - Effect of shear stress on adhering polyelectrolyte capsules.
AB  - A parallel plate flow chamber was implemented to study the deformation and
      adhesion of individual spherical hollow polyelectrolyte multilayered shells
      adhering to a coated surface. The device provides a well-defined laminar flow
      allowing the determination of the shear stress to which the capsules are being
      exposed up to 15 N/m(2). The results of the investigations indicate a strong
      dependence of the adhesion and mechanical resistance on the capsule size and wall
      thickness. Thin walled capsules, constituted of 8 polyelectrolyte layers
      (thickness congruent with 12 nm), are immediately deformed when exposed to flow
      while thick capsules, constituted of 16 layers (thickness congruent with 24 nm),
      of equal dimensions are detached from the surface for drag forces below 50 nN. It
      was observed that adhering capsules exposed to flow undergo an increase in their
      adhesion area in the direction of flow, resulting in rolling of the capsules. It
      was also found that the resistance of the capsules decreases after acetone
      treatment, indicating a weakening of the polyelectrolyte multilayer structure in
      the presence of this solvent.

PMID- 15476776
TI  - The interfacial dilational properties of hydrophobically modified associating
      polyacrylamide studied by the interfacial tension relaxation method at an oil
      water interface.
AB  - The interfacial dilational viscoelastic properties of hydrophobically associating
      block copolymer composed of acrylamide (AM) and a low amount of 2-phenoxylethyl
      acrylate (POEA) (<1.0 mol%) at the octane-water interfaces were studied by means
      of the interfacial tension relaxation method. The dependencies of interfacial
      dilational elasticity and viscous component on the dilational frequency were
      investigated. The interaction of hydrophobically associating block copolymer
      [P(AM/POEA)] with sodium dodecyl sulfate (SDS) has been explored. The results
      show that at lower frequency, the dilational elasticity for different
      concentration copolymer is close to zero; at higher frequency, the dilational
      elasticity shows no change with increased frequency; At moderate frequency (10(
      3)-1 Hz), the dilational elasticity decreased with a decrease in the dilational
      frequency. The results show that the hydrophobic groups of [P(AM/POEA)] chains
      can be associated by inter- or intrachain liaisons in water solution. The
      dilational viscous component for P(AM/POEA) comes forth a different maximum value
      at different frequencies when the polymer concentration is different. It is
      generally believed that the dilational viscous component reflects the summation
      of the various microscopic relaxation processes at and near the interface and
      different relaxation processes have different characteristic frequencies. The
      spectrum of dilational viscous component may appear more than once maximum values
      at different frequencies. The influence of SDS on the limiting dilational
      elasticity and viscous component for polymer solution was elucidated. For 5000
      ppm polymer solution, the limiting dilational elasticity decreased with an
      increase in SDS concentration. The dilational viscous component passed through a
      maximum value with a rise in the dilational frequency, which appeared at
      different frequency when SDS concentration is different; and the higher is the
      concentration, the lower is the dilational frequency. It can be explained that
      macromolecules may be substituted by SDS molecules in the interface and the
      interaction of molecules decrease, which makes the limiting dilational elasticity
      decrease. For 200 ppm polymer solution, the limiting dilational elasticity
      increased firstly and then decreased with SDS concentration increasing. This may
      be explained that the interfacial polymer concentration is so low that SDS
      molecules absorbed in the interface dominate dilational properties of the
      interfacial film even at very low SDS concentration. However, SDS molecules can
      gradually substitute the polymer molecules in the interface with a rise in SDS
      concentration, which results in the decrease in the limiting dilational
      elasticity.

PMID- 15476777
TI  - Two-dimensional Monte Carlo simulations of a polydisperse colloidal dispersion
      composed of ferromagnetic particles for the case of no external magnetic field.
AB  - We have investigated the aggregation phenomena in a polydisperse colloidal
      dispersion composed of ferromagnetic particles by means of the cluster-moving
      Monte Carlo method. The results have been compared with those for a monodisperse
      system. The internal structures of aggregates have been analyzed in terms of the
      radial distribution function in order to clarify the quantitative differences in
      the internal structures of clusters. In addition, the cluster size distribution
      and angular distribution function have been investigated. The results obtained in
      the present study are summarized as follows. In a monodisperse system, open
      necklacelike clusters are formed and they extend with increasing strength of the
      magnetic particle-particle interaction. In a polydisperse system with a small
      standard deviation in the particle size distribution, sigma=0.2, larger
      necklacelike clusters are formed and some looplike clusters can also be observed.
      In a polydisperse system with a larger standard deviation, sigma=0.35, clumplike
      clusters are formed for a weak magnetic particle-particle interaction. For a
      stronger magnetic interaction, larger size clusters that exhibit a complicated
      network structure are formed. These complicated cluster formations found in a
      polydisperse system are mainly due to the effect of the presence of larger
      particles.

PMID- 15476778
TI  - Aggregation behavior of single-walled carbon nanotubes in dilute aqueous
      suspension.
AB  - The aggregation behavior of colloidal single-walled carbon nanotubes (SWNT) in
      dilute aqueous suspensions was investigated using a novel light scattering
      measurement technique. The aggregation of SWNT in three suspensions was examined:
      (1) nanotubes after acid treatment; (2) as-received nanotubes stabilized by a
      nonionic surfactant; and (3) acid-treated nanotubes with nonionic surfactant.
      Continuous light scattering measurements of the SWNT suspensions (probing the 38
      436 nm length scale) made over two weeks showed that the nanotubes in each sample
      formed networks with fractal-like structures. The as-received nanotubes were
      stable over the measurement period, while the acid-treated nanotube suspension
      showed greater dispersion variability over time, yielding looser structures at
      large length scales and more compact structures at smaller length scales. The
      addition of surfactant to the acid-treated suspension significantly enhanced
      nanotube dispersion.

PMID- 15476779
TI  - Variation in surface energy heterogeneity of graphite due to adsorption of
      polyoxyethylene sorbitan monooleate.
AB  - The heterogeneity of surface energy of graphite before and after adsorption of
      polyoxyethylene sorbitan monooleate (Tween80) was investigated by the nitrogen
      adsorption technique. The nitrogen adsorption energy distributions (AEDs) were
      calculated from the low-pressure isotherm data (i.e., the data of submonolayer
      adsorption) according to the regularization method. Based on the AED of pristine
      graphite, two types of dominant energetic surface are identified and assigned
      respectively to the basal surface and the irregular surface, including the
      stepped edges and defect sites. When the adsorption amount of Tween80 is raised,
      both the surface energy and the energy heterogeneity of graphite gradually
      decline. It is thus demonstrated that Tween80 prefers interacting with and
      screening higher energetic surfaces to lower ones.

PMID- 15476780
TI  - Validation of cross-flow ultrafiltration for sampling of colloidal particles from
      aquatic systems.
AB  - The use of cross-flow ultrafiltration (CFF) for the isolation of colloids from
      the bulk aquatic matrices has been increasing over the last decade; however, a
      thorough validation of each CFF system is needed before its application to
      natural samples. Laboratory experiments have been conducted to validate a 1-kDa
      Millipore Pellicon 2 cartridge type CFF system, using a range of molecular probes
      spiked in natural waters. Using the separation data of these probes, key
      validation parameters have been calculated, including retention coefficient (RC),
      concentration factor (cf), colloid concentration, recovery, and mass balance. The
      permeation behaviour of these molecules has also been studied using a simple
      permeation model. Results show that good retention (>80%) of high molecular
      weight (HMW, >1 kDa) molecules and low retention (<20%) of low molecular weight
      (LMW, <1 kDa) molecules can be achieved at high cf values or over long
      timescales. In addition, permeation modelling and the calculation of colloid
      concentration demonstrate the same findings, again recommending high cf values or
      long timescales for ultrafiltration to minimise the retention of LMW molecules.
      The retention characteristics of 3-kDa dextran change slightly with salinity.
      Mass balance calculations show good recoveries for all of the molecules tested.
      The apparent membrane molecular cut-off of the CFF system has been estimated to
      be between 2.1 and 2.5 kDa, which is slightly greater than the manufacturer's
      nominal MW cut-off of 1 kDa.

PMID- 15476781
TI  - Interaction between dissimilar double layers with like signs under charge
      regulation on the basis of the Gouy-Chapman-Stern-Grahame model.
AB  - The force of interaction between two flat double layers with dissimilar surface
      potentials but of the same signs, in contact with 1-1 electrolyte solutions
      (0.001, 0.01, and 0.1 M), was calculated as a function of the surface separation.
      The calculation was carried out on the basis of the Gouy-Chapman-Stern-Grahame
      double-layer model, incorporating the site-dissociation and site-binding model
      used previously for many oxide studies. The results demonstrated that the
      interaction force under surface charge regulation was always repulsive,
      increasing progressively with decreasing surface separation. This result is in
      contrast to the predictions of previous theories that are based on the Gouy
      Chapman (GC) double-layer model. Dependence of surface potentials and surface
      charge densities on the surface separation is also presented.

PMID- 15476782
TI  - A rapidly convergent series for computation of the interaction between two
      similar plane-parallel double layers.
AB  - A rapidly convergent series for computation of the interaction between two
      similar plane-parallel double layers is derived by expanding the interaction
      energy in power series of omega(0)(omega(0)<tanh y(0)|64). The series terms
      required to obtain the interaction energy with six significant figures do not
      exceed 1 when the dimensionless surface potential y(0) of colloid particles is
      less than or equal to 2.00000 x 10.

PMID- 15476783
TI  - Investigation of the properties of oil at the bleaching unit of an oil refinery.
AB  - Color removal from neutralized sunflower oil was studied with different kinds of
      commercial bleaching earths. The effect of changes in time (25 and 35 min),
      temperature (80-125 degrees C), and bleaching earth dosage (0.1-0.9% by weight)
      on color, chlorophyll and carotene concentrations, and oxidation degree were
      investigated. To obtain adsorption curves from coloring compounds adsorbed onto
      activated bleaching earths, the Langmuir and Freundlich equations was used, the
      constant parameters and correlation coefficient R were calculated for each type
      of bleaching earth, and color changes were explained by both adsorption
      isotherms. It was observed that an increase in bleaching earth dosage decreases
      color. Its effect on oxidation state, however, is complex and related to both
      primary and secondary oxidation products. In addition, an increase in temperature
      seems to decrease chlorophyll and carotene adsorptions. Generally, time beyond
      equilibrium is considered useless for the removal of unwanted components. This
      study also confirms this claim and reveals that the peroxide value does not
      indicate the oxidation state of the oil completely.

PMID- 15476784
TI  - A simple simulation methodology for estimation of dehydration energies and
      surface potentials of concentrated NaCl solutions.
AB  - A novel simulation procedure for estimating the dehydration energies of NaCl
      solutions spanning a wide range of concentrations, which incorporates ionic and
      molecular sizes, ion-pair formation, etc., is proposed on geometric and
      phenomenological considerations. The extent of dehydration during each movement
      of the hydrated molecule is evaluated using the expected and actual displacement
      of the species and mean nearest-neighbor distances. The interdependence between
      the size of the simulation box, number of molecules, and electrolyte
      concentration is pointed out.

PMID- 15476785
TI  - Ionic liquid ion sources: suppression of electrochemical reactions using voltage
      alternation.
AB  - The problem of electrochemical decomposition due to extraction of single polarity
      ions from a novel ionic liquid ion source (ILIS) is solved by periodically
      alternating the voltage source so that the potential difference that appears
      across the double layer formed between the emitter conductive material and the
      liquid is maintained below the electrochemical window limit, thus eliminating
      electronic reactions. The ionic liquid EMI-BF(4) is used to externally wet a
      solid tungsten emitter, establishing a physical boundary with a certain liquid
      metal contact area. Theoretical and experimental evidence suggests that this area
      is close to the effective surface involved in the double layer charging dynamics.
      The extent of this surface is relatively large, thus increasing the net
      capacitance and consequently the double layer charging time, demonstrating that
      low frequency voltage alternation of the order of 1 Hz is enough to obtain clean
      and reliable ion emission.

PMID- 15476786
TI  - Interface motion of capillary-driven flow in rectangular microchannel.
AB  - In microchannel flow, gas-liquid interface behavior is important for developing a
      wide range of microfluidic applications, especially in passive microfluidic
      systems. This paper presents a discussion of interface motion driven by capillary
      action in a microchannel. We have extended the theory beyond the previous theory
      of capillary rise problem for a circular tube, to a rectangular microchannel. The
      same formula for the relation between nondimensional time and interface position
      is obtained as for a circular tube. We examined rectangular microchannels with
      several sizes (about 50 to 100 microm square) of glass capillaries and 85 x 68
      microm and 75 x 45 microm polydimethylsiloxane (PDMS) microchannels fabricated by
      photolithography technique, respectively. We observed movement of the gas-liquid
      interface position and compared it to the dimensionless relation. We obtained the
      value of a dimensionless variable of driving force that is related to dynamic
      contact angles for glass-water, glass-ethanol, and PDMS-ethanol. Using this
      variable, interface motion can be predicted for any size of rectangular channels.

PMID- 15476787
TI  - Viscous flow of a volatile liquid on an inclined heated surface.
AB  - We investigate the effects of evaporation on a gravity-driven flow of a viscous
      liquid on a heated solid surface. Vapor molecules are adsorbed on the dry areas
      of the solid and form a microscopic adsorbed film. The thickness of this film is
      calculated from the formulas for disjoining pressure and the principles of
      equilibrium thermodynamics. A lubrication-type approach is used to derive an
      evolution equation capable of describing both the macroscopic shape of the vapor
      liquid interface and the adsorbed film on the vapor-solid interface. Under the
      conditions of negligible evaporation, the numerical solution of the evolution
      equation predicts translational motion and formation of capillary ridge, in
      agreement with previous investigations. Moderate evaporation is shown to slow
      down the flow and decrease the height of the capillary ridge, which implies a
      stabilizing effect of evaporation on the well-known instability observed in
      gravity-driven thin film flows. We also study the combined effects of evaporation
      and thermocapillary stresses and show that the latter act to reduce the velocity
      of the downward motion, but increase the height of the capillary ridge. Apparent
      contact angles are found from the solution and shown to increase with evaporation
      and contact line speed. For strong evaporation, steady state solutions are found
      such that evaporation balances the downward motion of the interface under the
      action of gravity.

PMID- 15476788
TI  - Effect of temperature on the surface free energy of amorphous carbon films.
AB  - Diamond-like carbon (DLC) and tetrahedral amorphous carbon (ta-C) have attracted
      much attention recently for biomedical and antifouling applications due to their
      excellent biocompatibility and inherent nonstick properties. It has been
      demonstrated that the solid surface free energy is a dominant factor in cellular
      or fouling adhesion. However, few data for the surface free energy of DLC and ta
      C coatings at temperatures in the range 37-95 degrees C are available. In this
      study DLC and ta-C coatings on stainless steel 304 sheets were prepared using an
      unbalanced magnetron sputtering system and a filtered cathodic vacuum arc system,
      respectively. The contact angles of water, diiodomethane and ethylene glycol on
      the coated surfaces at temperatures in the range 20-95 degrees C were measured
      using a Dataphysics OCA-20 contact angle analyzer. The surface free energy of the
      coatings and their components (e.g., dispersion, polar or acid/base portions)
      were calculated using various methods. The experimental results showed that the
      total surface free energy and dispersive surface free energy of the ta-C
      coatings, DLC coatings, stainless steel 304 and titanium decreased with
      increasing surface temperature, while the acid-base SFE component increased with
      increasing temperature.

PMID- 15476789
TI  - Interfacial activity of copper(II) complexes with chelating ligands and
      individual hydrophobic extractants in model extraction systems I. Study of
      equilibrium interfacial tension at the hydrocarbon/water interface for systems
      with copper(II) complexes with chelating ligands and individual hydrophobic
      extractants.
AB  - The equilibrium interfacial tensions at the hydrocarbon/water interfaces, as
      measured at 20 degrees C for copper(II) complexes with the chelating ligands beta
      diketone (1-phenyl-1,3-decanedione), 2-hydroxy-5-t-nonylacetophenone oxime, 2
      hydroxy-5-t-octylacetophenone and 2-hydroxy-5-t-octylbenzophenone oxime, as well
      as for individual extractants, are discussed. The interfacial tension and surface
      excess isotherms were determined and interpreted. The experimentally obtained
      curves were successfully matched with the Szyszkowski and Frumkin equations. It
      was found that the tendencies of interfacial tension to be lower at the
      hydrocarbon/water interfaces for copper(II) complexes and individual chelating
      ligands are similar. However, the effectiveness and efficiency of adsorption for
      chelating extractants and copper(II) complexes are quite different, irrespective
      of the type of hydrocarbon used as the organic diluent. On the other hand, the
      type of organic phase affects the interfacial activity of the investigated
      compounds. Moreover, it was shown that the way of preparing the measurement
      systems with the copper(II) complex influences the results of its interfacial
      activity.

PMID- 15476790
TI  - Spreading of nanofluids driven by the structural disjoining pressure gradient.
AB  - This paper discusses the role of the structural disjoining pressure exerted by
      nanoparticles on the spreading of a liquid film containing these particles. The
      origin of the structural disjoining pressure in a confined geometry is due to the
      layering of the particles normal to the confining plane and has already been
      traced to the net increase in the entropy of the system in previous studies. In a
      recent paper, Wasan and Nikolov (Nature, 423 (2003) 156) pointed out that the
      structural component of the disjoining pressure is strong enough to move a liquid
      wedge; this casts a new light on many applications-most notably, detergency.
      While the concept of spreading driven by the disjoining pressure is not new, the
      importance of the structural disjoining pressure arises from its long-range
      nature (as compared to the van der Waals' force), making it an important
      component of the overall force balance near the contact line. In this paper, we
      report on a parametric study of the spreading phenomena by examining the effects
      of nanoparticle size, concentration and polydispersity on the displacement of an
      oil-aqueous interface with the aqueous bulk containing nanoparticles. The
      solution of the extended Laplace-Young equations for the profile of the meniscus
      yields the position of the nominal contact line under the action of the
      structural disjoining pressure. Simulations show that the displacement of the
      contact line is greater with a high nanoparticle volume fraction, small particles
      for the same volume fraction, monodispersed (in size) particles rather than
      polydispersed particles and when the resisting capillary pressure is small, i.e.,
      when the interfacial tension is low and/or the radius of the dispersed phase
      drop/bubble is large.

PMID- 15476791
TI  - The 3D structure of real polymer foams.
AB  - The intricate structure of polymeric foams may be examined using 3D imaging
      techniques such as MRI or X-ray tomography followed by image processing. Using a
      new 3D image processing technique, six images of polyurethane foams were analyzed
      to create computerized 3D models of the samples. Measurements on these models
      yielded distributions of many microstructural features, including strut length
      and window and cell shape distributions. Nearly 8000 struts, 4000 windows, and
      376 cells were detected and measured in six polyurethane foam samples. When
      compared against previous theories and studies, these measurements showed that
      the structure of real polymeric foams differs significantly from both equilibrium
      models and aqueous foams. For example, previous studies of aqueous foams showed
      that about 70% of foam windows were pentagons. In the polymeric sample studied
      here, only 55% of windows were pentagonal.

PMID- 15476792
TI  - Elucidation of the isomeric domains formed by sodium N-dodecanoyl-L-prolinate.
AB  - Investigations aimed at clarifying the nature of geometrical domains of amidic
      sodium N-dodecanoyl-l-prolinate are reported. NMR investigations on the
      association of aromatic solutes with the aggregates formed by the amidic
      surfactant in water show the selective binding of some solutes to the Z domains.
      Fluorescence quenching experiments allowed us to measure the aggregation number
      of the aggregates. SAXS experiments gave the average size and structural features
      of the aggregates. A NMR ROESY experiment evidenced the mosaic-like nature of the
      domains inside the same aggregate.

PMID- 15476793
TI  - Micellization of block copolymer P94 in aqueous solution.
AB  - P94 is a triblock copolymer of poly(oxyethylene) and poly(oxypropylene), type
      EPE. Eluent gel permeation chromatography has been used to demonstrate the
      formation of large micelles in solutions of the copolymer at temperatures
      immediately above the critical micelle temperature. Values of the critical
      micelle temperature (cmt) obtained in this way are in excellent agreement with
      results from differential scanning calorimetry and surface tensiometry. A van't
      Hoff plot was used to define the concentration dependence of the cmt for dilute
      solutions (c < or =2 wt%) and to obtain an apparent value of the standard
      enthalpy of micellization. Using published data, comparison is made with the
      thermodynamics of micellization in concentrated solution (c > or =20 wt%).

PMID- 15476794
TI  - Evolution of liquid holdup profile in a standing protein stabilized foam.
AB  - Evolution of liquid holdup profile in a standing foam formed by whipping and
      stabilized by sodium caseinate in the presence of xanthan gum when subjected to
      16 and 29g centrifugal force fields was measured using magnetic resonance imaging
      for different pH, ionic strength, protein and xanthan gum concentrations.
      Drainage resulted in the formation of a separate liquid layer at the bottom at
      longer times. Foam drainage was slowest at pH 7, lower ionic strength, higher
      protein and gum concentrations. Foam was found to be most stable at pH 5.1 near
      the isoelectric point of protein, lower ionic strength and higher protein and
      xanthan gum concentrations. A predicted equilibrium liquid holdup profile based
      on a previous model (G. Narsimhan, J. Food Eng. 14 (1991) 139) agreed well with
      experimental values at sufficiently long times. A proposed model for velocity of
      drainage of a power law fluid in a Plateau border for two different simplified
      geometries was incorporated in a previously developed model for foam drainage (G.
      Narsimhan, J. Food Eng. 14 (1991) 139) to predict the evolution of liquid holdup
      profiles. The model predictions for simplified circular geometry of Plateau
      border compared well with the experimental data of liquid holdup profiles at
      small times. At longer times, however, the predicted liquid holdup profile was
      larger than the observed, this discrepancy being due to coarsening of bubble size
      and decrease in foam height not accounted for in the model. A Newtonian model for
      foam drainage under predicted drainage rates did not agree with the experimental
      data.

PMID- 15476795
TI  - Selectivity and stability of organic films at the air-aqueous interface.
AB  - It has recently been determined that organic compounds represent a significant
      percentage of the composition of certain atmospheric aerosols. Amphiphilic
      organics, such as fatty acids and alcohols, partition to the interface of aqueous
      aerosols. In this way, the air-aqueous interface of an aerosol has the ability to
      act as both a concentrator and a selector of organic surfactants. Isotherms of
      nonanoic acid, stearic acid, 1-octadecanol, and a binary of mixture of nonanoic
      and stearic acids were used to infer the packing ability and molecular
      orientation of the surfactants at the interface. The selectivity of the air
      aqueous interface was studied by monitoring the composition of binary organic
      films as a function of film exposure time. The films were formed, aged, and
      collected with the use of a Langmuir trough. The composition of the aged film was
      determined via GC-MS. Surfactants with differing carbon number and chemical
      functionalities were studied. These included stearic acid, lauric acid, 1
      octadecanol, and octadecane. The stability and packing ability of stearic and
      lauric acid films were examined as a function of subphase pH. The relevance of
      these findings as they relate to the composition and structure of organic
      aerosols as well as recent surface-sensitive aerosol field measurements is
      discussed.

PMID- 15476796
TI  - Phase diagrams of nonionic foam films: construction by means of disjoining
      pressure versus thickness curves.
AB  - The thickness h of foam films can be measured as a function of the disjoining
      pressure Pi using a thin film pressure balance. Experimental Pi-h curves of foam
      films stabilized with nonionic surfactants measured at various concentrations
      resemble the p-V(m) isotherms of real gases measured at various temperatures (p
      is the pressure and V(m) is the molar volume of the gas). This observation led us
      to adopt the van der Waals approach for describing real gases to thin foam films,
      where the thickness h takes the role of V(m) and the disjoining pressure Pi
      replaces the ordinary pressure p. Our analysis results in a phase diagram for a
      thin foam film with spinodal, binodal as well as a critical point. The thicker
      common black film corresponds to the gas phase and the compact Newton black film
      for which the two surfaces are in direct contact corresponds to the dense liquid.
      We show that the tuning parameter for the phase behavior of the film is the
      surface charge density, which means that Pi-h curves should not be referred to as
      isotherms. In addition to the equilibrium properties the driving force for the
      phase transition from a common black film to a Newton black film or vice versa is
      calculated. We discuss how this transition can be controlled experimentally.

PMID- 15476797
TI  - Electrophoresis of a sphere at an arbitrary position in a spherical cavity filled
      with Carreau fluid.
AB  - Boundary effects on the electrophoretic behavior of a charged entity are of both
      fundamental and practical significance. Here, they are examined by considering
      the case where a sphere is at an arbitrary position in a spherical cavity under
      conditions of low surface potential and weak applied electrical field. Previous
      analyses are extended to the case of a non-Newtonian fluid, and a Carreau model
      is adopted for this purpose. The effects of key parameters such as the thickness
      of a double layer, the relative sizes of particle and cavity, the position of a
      particle, and the nature of a fluid on the electrophoretic mobility of a particle
      are discussed. Several interesting phenomena are observed. For example, if the
      applied electric field points toward north, the mobility of a particle has a
      local maximum when it is at the center of a cavity. However, if a particle is
      sufficiently close to the north pole of a cavity, its mobility exhibits a local
      minimum as its position varies. This does not occur when the particle is close to
      the south pole of the cavity; instead, it may move in the direction opposite to
      that of the applied electric field. For a Newtonian fluid, if a particle is close
      to the north pole of a cavity, its upward movement yields a clockwise
      (counterclockwise) vortex near the north pole of the cavity and a
      counterclockwise (clockwise) vortex near the south pole of the cavity on its
      right (left)-hand side. The latter is not observed for a Carreau fluid.

PMID- 15476798
TI  - The shear viscosity of polyampholyte (gelatin) stabilized colloidal dispersions.
AB  - A micromechanical model for the zero shear viscosity of polyampholyte-stabilized
      colloidal dispersions based on the osmotic overlap potential is proposed and
      tested against model system measurements. This model relates the shear viscosity
      of polyampholyte-stabilized colloidal dispersions to the oncotic pressure of
      polyampholyte solutions through an interparticle potential and an effective hard
      sphere scaling. The results of viscosity calculations based on independently
      measured parameters compare favorably to experimental measurements on model,
      silica dispersions stabilized with adsorbed photographic grade gelatin. The
      results support a direct link between the capacity of polyampholytes and
      polyelectrolytes to stabilize dispersions and control dispersion viscosity and
      their solution oncotic pressure. The model is also demonstrated to provide a
      master curve for literature data for the zero shear viscosity of polyampholyte
      stabilized colloidal dispersions.

PMID- 15476799
TI  - Micelles and reverse micelles in the nickel bis(2-ethylhexyl)
      sulfosuccinate/water/isooctane microemulsion.
AB  - The ternary system Ni(2+)(AOT)(2) (nickel 2-bis[2-ethylhexyl]
      sulfosuccinate)/water/isooctane presents w/o and o/w microemulsions with a Winsor
      progression (2Phi-3Phi-2Phi), without the addition of salt; the "fish diagram"
      was obtained for alpha=0.5 and gamma=0.02-0.22. Using static and dynamic light
      scattering the micellar size, the ratio of water to surfactant, and the density
      of micelles for this system were estimated. In addition, the mean interfacial
      curvature as a function of temperature was obtained.

PMID- 15476800
TI  - Comment on "A broad frequency range dielectric spectrometer for colloidal
      suspensions: cell design, calibration, and validation".
AB  - Recently, a simple analytical model was derived from the standard electrokinetic
      theory to deal with electrode polarization in low frequency dielectric
      measurements [Hollingsworth and Saville, J. Colloid Interface Sci. 257 (2003) 65
      76]. Comparisons were made between dielectric constant-frequency relationships
      extracted from data on electrolyte solutions using the analytical model and the
      well-known RC-circuit analog. Electrolyte spectra interpreted with the analytical
      approach remained smooth (and constant) down to much lower frequencies than was
      the case with the RC model. It was also shown how the RC model arises naturally
      from the analytical model as an asymptotic expansion in inverse powers of the
      electrode spacing. Numerical calculations indicated substantial differences
      between the two models at low frequencies due to higher order terms omitted in
      the RC model. As it turns out, the comparison contained a numerical error. Here
      we revisit the methodology to show that although the two formulations disagree,
      they do so (in a numerical sense) only at much smaller electrode separations than
      those used in the aforementioned example. The purpose of this Letter is to
      correct the numerical error and show, explicitly, how the RC-circuit analog
      coefficients are related to the asymptotic expansion at low frequencies.

PMID- 15476801
TI  - Motifs of two small residues can assist but are not sufficient to mediate
      transmembrane helix interactions.
AB  - Both experimental and statistical searches for specific motifs that mediate
      transmembrane helix-helix interactions showed that two glycine residues separated
      by three intervening residues (GxxxG) provide a framework for specific
      interactions. Further work suggested that other motifs of small residues can
      mediate the interaction of transmembrane domains, so that the AxxxA-motif could
      also drive strong interactions of alpha-helices in soluble proteins. Thus, all
      these data indicate that a motif of two small residues in a distance of four
      might be enough to provide a framework for transmembrane helix-helix interaction.
      To test whether GxxxG is equivalent to (small)xxx(small), we investigated the
      effect of a substitution of either of the two Gly residues in the glycophorin A
      GxxxG-motif by Ala or Ser using the recently developed GALLEX system. The results
      of this mutational study demonstrate that, while a replacement of either of the
      two Gly by Ala strongly disrupts GpA homo-dimerization, the mutation to Ser
      partly stabilizes a dimeric structure. We suggest that the Ser residue can form a
      hydrogen bond with a backbone carbonyl group of the adjacent helix stabilizing a
      preformed homo-dimer. While (small)xxx(small) serves as a useful clue, the
      context of adjacent side-chains is essential for stable helix interaction, so
      each case must be tested.

PMID- 15476802
TI  - Mutational and structural analysis of stem-loop IIIC of the hepatitis C virus and
      GB virus B internal ribosome entry sites.
AB  - Translation of the open reading frames (ORF) of the hepatitis C virus (HCV) and
      closely related GB virus B (GBV-B) genomes is driven by internal ribosome entry
      site (IRES) elements located within the 5' non-translated RNA. The functioning of
      these IRES elements is highly dependent on primary and higher order RNA
      structures. We present here the solution structures of a common, critical domain
      within each of these IRESs, stem-loop IIIc. These ten-nucleotide hairpins have
      nearly identical sequences and similar overall tertiary folds. The final refined
      structure of each shows a stem with three G:C base-pairs and a novel tetraloop
      fold. Although the bases are buckled, the first and fourth nucleotides of both
      tetraloops form a Watson-Crick type base-pair, while the apical nucleotides are
      located in the major groove where they adopt C(2)-endo sugar puckering with B
      form geometry. No hydrogen bonding interactions were observed involving the two
      apical residues of the tetraloop. Stability of the loops appears to be derived
      primarily from the stacking of bases, and the hydrogen bonding between the fourth
      and seventh residues. Mutational analysis shows that the primary sequence of stem
      loop IIIc is important for IRES function and that the stem and first and fourth
      nucleotides of the tetraloop contribute to the efficiency of internal ribosome
      entry. Base-pair formation between these two positions is essential. In contrast,
      the apical loop nucleotides differ between HCV and GBV-B, and substitutions in
      this region of the hairpin are tolerated without major loss of function.

PMID- 15476803
TI  - Structure and function of the C-terminal domain of the polymerase cofactor of
      rabies virus.
AB  - The phosphoprotein (P) of rabies virus binds the viral polymerase to the
      nucleoprotein (N)-RNA template for transcription and replication. By limited
      protease digestion we defined a monomeric C-terminal domain of P that can bind to
      N-RNA. The atomic structure of this domain was determined and previously
      described mutations that interfere with binding of P to N-RNA could now be
      interpreted. There appears to be two features involved in this activity situated
      at opposite surfaces of the molecule: a positively charged patch and a
      hydrophobic pocket with an exposed tryptophan side-chain. Other previously
      published work suggests a conformational change in P when it binds to N-RNA,
      which may imply the repositioning of two helices that would expose a hydrophobic
      groove for interaction with N. This domain of rabies virus P is structurally
      unrelated to the N-RNA binding domains of the phosphoproteins of Sendai and
      measles virus that are members of the same order of viruses, the non-segmented
      negative strand RNA viruses. The implications of this finding for the evolution
      of this virus group are discussed.

PMID- 15476804
TI  - Mechanistic insights from the structures of HincII bound to cognate DNA cleaved
      from addition of Mg2+ and Mn2+.
AB  - The three-dimensional X-ray crystal structures of HincII bound to cognate DNA
      containing GTCGAC and Mn(2+) or Mg(2+), at 2.50A and 2.95A resolution,
      respectively, are presented. In both structures, the DNA is found cleaved, and
      the positions of the active-site groups, cleaved phosphate group, and 3' oxygen
      atom of the leaving group are in very similar positions. Two highly occupied
      Mn(2+) positions are found in each active site of the four crystallographically
      independent subunit copies in the HincII/DNA/Mn(2+) structure. The manganese ion
      closest to the previously identified single Ca(2+) position of HincII is shifted
      1.7A and has lost direct ligation to the active-site aspartate residue, Asp127. A
      Mn(2+)-ligated water molecule in a position analogous to that seen in the
      HincII/DNA/Ca(2+) structure, and proposed to be the attacking nucleophile, is
      beyond hydrogen bonding distance from the active-site lysine residue, Lys129, but
      remains within hydrogen bonding distance from the proRp oxygen atom of the
      phosphate group 3' to the scissile phosphate group. In addition, the position of
      the cleaved phosphate group is on the opposite side of the axis connecting the
      two metal ions relative to that found in the BamHI/product DNA/Mn(2+) structure.
      Mechanistic implications are discussed, and a model for the two-metal-ion
      mechanism of DNA cleavage by HincII is proposed.

PMID- 15476805
TI  - Electrostatic interactions and the folding of the four-way DNA junction: analysis
      by selective methyl phosphonate substitution.
AB  - The structure and dynamics of the four-way (Holliday) junction are strongly
      dependent on the presence of metal ions. In this study, the importance of
      phosphate charge in and around the point of strand exchange has been explored by
      selective replacement with electrically neutral methyl phosphonate groups, guided
      by crystal structures of the junction in the folded, stacked X conformation.
      Junction conformation has been analysed by comparative gel electrophoresis and
      fluorescence resonance energy transfer (FRET). Three of sets of phosphate groups
      on the exchanging strands have been analysed; those at the point of strand
      exchange and those to their 3' and 5' sides. The exchanging and 3' phosphate
      groups form a box of negatively charged groups on the minor groove face of the
      junction, while the 5' phosphate groups face each other on the major groove side,
      with their proR oxygen atoms directed at one another. The largest effects are
      observed on substitution of the exchanging phosphate groups; replacement of both
      groups leads to the loss of the requirement for addition of metal ions to allow
      junction folding. When the equivalent phosphate groups on the continuous strands
      were substituted, a proportion of the junction folded into the alternative
      conformer so as to bring these phosphate groups onto the exchanging strands.
      These species did not interconvert, and thus this is likely to result from the
      alternative diasteromeric forms of the methyl phosphonate group. This shows that
      some of the conformational effects result from more than purely electrostatic
      interactions. Smaller but significant effects were observed on substitution of
      the flanking phosphate groups. All methyl phosphonate substitutions at these
      positions allowed folding to proceed at a reduced concentration of magnesium
      ions, with double substitutions more effective than single substitutions.
      Substitution of 5' phosphates resulted in a greater degree of folding at a given
      ionic concentration compared to the corresponding 3' phosphate substitutions.
      These results show that the phosphate groups at the point of strand exchange
      exert the largest electrostatic effect on junction folding, but a number of
      phosphate groups in the vicinity of the exchange region contribute to the overall
      effects.

PMID- 15476806
TI  - Thermodynamic signature of GCN4-bZIP binding to DNA indicates the role of water
      in discriminating between the AP-1 and ATF/CREB sites.
AB  - The energetic basis of GCN4-bZIP complexes with the AP-1 and ATF/CREB sites was
      investigated by optical methods and scanning and isothermal titration
      microcalorimetry. The dissociation constant of the bZIP dimer was found to be
      significantly higher than that of its isolated leucine zipper domain: at 20
      degrees C it is 1.45microM and increases with temperature. To avoid complications
      from dissociation of this dimer, DNA binding experiments were carried out using
      an SS crosslinked version of the bZIP. The thermodynamic characteristics of the
      bZIP/DNA association measured at different temperatures and salt concentrations
      were corrected for the contribution of refolding the basic segment upon binding,
      determined from the scanning calorimetric experiments. Fluorescence anisotropy
      titration experiments showed that the association constants of the bZIP at 20
      degrees C with the AP-1 and ATF/CREB binding sites do not differ much, being
      1.5nM and 6.4nM, corresponding to Gibbs energies of -49kJmol(-1) and -46kJmol(
      1), respectively. Almost half of the Gibbs energy is attributable to the
      electrostatic component, resulting from the entropic effect of counterion release
      upon DNA association with the bZIP and is identical for both sites. In contrast
      to the Gibbs energies, the enthalpies of association of the fully folded bZIP
      with the AP-1 and ATF/CREB sites, and correspondingly the entropies of
      association, are very different. bZIP binding to the AP-1 site is characterized
      by a substantially larger negative enthalpy and non-electrostatic entropy than to
      the ATF/CREB site, implying that the AP-1 complex incorporates significantly more
      water molecules than the ATF/CREB complex.

PMID- 15476807
TI  - A structural similarity analysis of double-helical DNA.
AB  - A database of the structural properties of all 32,896 unique DNA octamer
      sequences has been calculated, including information on stability, the minimum
      energy conformation and flexibility. The contents of the database have been
      analysed using a variety of Euclidean distance similarity measures. A global
      comparison of sequence similarity with structural similarity shows that the
      structural properties of DNA are much less diverse than the sequences, and that
      DNA sequence space is larger and more diverse than DNA structure space. Thus,
      there are many very different sequences that have very similar structural
      properties, and this may be useful for identifying DNA motifs that have similar
      functional properties that are not apparent from the sequences. On the other
      hand, there are also small numbers of almost identical sequences that have very
      different structural properties, and these could give rise to false-positives in
      methods used to identify function based on sequence alignment. A simple
      validation test demonstrates that structural similarity can differentiate between
      promoter and non-promoter DNA. Combining structural and sequence similarity
      improves promoter recall beyond that possible using either similarity measure
      alone, demonstrating that there is indeed information available in the structure
      of double-helical DNA that is not readily apparent from the sequence.

PMID- 15476808
TI  - Periodicities of 10-11bp as indicators of the supercoiled state of genomic DNA.
AB  - DNA sequences contain information about the bendability and native conformation
      of DNA. For example, a repetition of certain dinucleotides at distances of 10
      11bp supports wrapping around nucleosomes and supercoiled structures of bacterial
      DNA. We analyzed 86 eubacterial genomes, 16 archaea, and six genomes of higher
      eukaryotes. First, we discuss whether or not the observed periodicities represent
      indeed bendability signals. This claim is confirmed since: (1) dinucleotide
      signals are of comparable size to mononucleotide signals, (2) the signals are
      present in non-coding DNA as well, and (3) repeat masking has only a minor effect
      on 10-11bp periodicities. Moreover, the periodicities persist up to 150bp,
      comparable to the nucleosome size. We show that doublet peaks in Caenorhabditis
      elegans and some prokaryotes can be traced back to long-ranging modulations. In
      mammalian genomes, we find consistently spectral peaks as observed earlier in
      human chromosomes 20, 21 and 22. It has been shown in previous studies that
      archaea have periods of 10bp, whereas eubacteria exhibit 11bp periodicities.
      These differences reflect different supercoiled states of microbial DNA. Is the
      period of 10bp an archaeal or a thermophilic feature? This question is addressed
      by relating periodicities to optimal growth temperatures. It turns out that the
      archaea Methanopyrus kandleri (t(opt)=80 degrees C) and a Halobacterium strain
      (t(opt)=42 degrees C) both have longer periods of about 11bp. Eubacterial genomes
      have consistently periods around 11bp indicative of negative supercoiling.

PMID- 15476809
TI  - In vivo homodimerisation of HTLV-1 Gag and MA gives clues to the retroviral
      capsid and TM envelope protein arrangement.
AB  - During retroviral particle formation, the capsid precursors (Gag) associate with
      the cell membrane via their matrix (MA) domain to form viral assembling
      particles. After budding, Gag and its proteolytically matured MA, form a shell in
      the released immature and mature particles, respectively. Although the
      arrangement of Gag domains in vitro and their radial organisation in retroviral
      particles have been extensively studied, little is known concerning Gag inter
      subunit interactions in authentic retroviruses. We report that human T-cell
      leukemia virus type 1 Gag homodimerises in the cell via a disulphide bonding at
      cysteine 61 in the MA domain. Most Gags are homodimeric after budding and MAs are
      also dimeric in mature authentic virions. Molecular modelling of the MA domain
      indicates that non-covalent interactions at the MA dimer interface may also be
      important for Gag (and MA) dimerisation. In addition, all amino acids previously
      reported to be involved in MA-transmembrane (TM) interactions are located on the
      MA face opposite to the dimer interface. The model reveals that homodimerisation
      is compatible with a hexameric network of Gag and MA dimers that look like the
      hexameric networks observed for other retroviruses. These data, together with
      previous studies, lead us to propose a supra-molecular arrangement model in which
      the transmembrane glycoproteins of the virion envelope are anchored in a
      hexameric cage hole formed by the MA.

PMID- 15476810
TI  - Structural flexibility of the N-terminal beta-barrel domain of 15-lipoxygenase-1
      probed by small angle X-ray scattering. Functional consequences for activity
      regulation and membrane binding.
AB  - Mammalian lipoxygenases form a heterogeneous family of lipid peroxidizing
      enzymes, which have been implicated in synthesis of inflammatory mediators, in
      cell development and in the pathogenesis of various diseases (atherosclerosis,
      osteoporosis) with major health political importance. The crystal structures of
      two plant lipoxygenase isoforms have been solved and X-ray coordinates for an
      inhibitor complex of the rabbit 15-lipoxygenase-1 are also accessible. Here, we
      investigated the solution structure of the ligand-free rabbit 15-lipoxygenase-1
      by small angle X-ray scattering. From the scattering profiles we modeled the
      solution structure of the enzyme using two independent ab initio approaches.
      Preliminary experiments indicated that at low protein concentrations (<1mg/ml)
      and at 10 degrees C the enzyme is present as hydrated monomer. Superposition of
      the high resolution crystal structure and our low resolution model of the
      solution structure revealed two major differences. (i) Although the two models
      are almost perfectly superimposed in the region of the catalytic domain the
      solution structure is stretched out in the region of the N-terminal beta-barrel
      domain and exhibits a bigger molecular volume. (ii) There is a central bending of
      the enzyme molecule in the solution structure, which does not show up in the
      crystal structure. Both structural peculiarities may be explained by a high
      degree of motional freedom of the N-terminal beta-barrel domain in aqueous
      solutions. This interdomain movement may be of functional importance for
      regulation of the catalytic activity and membrane binding.

PMID- 15476811
TI  - Charge translocation during cosubstrate binding in the Na+/proline transporter of
      E.coli.
AB  - Charge translocation associated with the activity of the Na(+)/proline
      cotransporter PutP of Escherichia coli was analyzed for the first time. Using a
      rapid solution exchange technique combined with a solid-supported membrane (SSM),
      it was demonstrated that Na(+)and/or proline individually or together induce a
      displacement of charge. This was assigned to an electrogenic Na(+)and/or proline
      binding process at the cytoplasmic face of the enzyme with a rate constant of
      k>50s(-1) which preceeds the rate-limiting step. Based on the kinetic analysis of
      our electrical signals, the following characteristics are proposed for substrate
      binding in PutP. (1) Substrate binding is electrogenic not only for Na(+), but
      also for the uncharged cosubstrate proline. The charge displacement associated
      with the binding of both substrates is of comparable size and independent of the
      presence of the respective cosubstrate. (2) Both substrates can bind individually
      to the transporter. Under physiological conditions, an ordered binding mechanism
      prevails, while at sufficiently high concentrations, each substrate can bind in
      the absence of the other. (3) Both substrate binding sites interact cooperatively
      with each other by increasing the affinity and/or the speed of binding of the
      respective cosubstrate. (4) Proline binding proceeds in a two-step process: low
      affinity (approximately 1mM) electroneutral substrate binding followed by a
      nearly irreversible electrogenic conformational transition.

PMID- 15476812
TI  - A new theory and algorithm for reconstructing helical structures with a seam.
AB  - Conventional helical reconstruction is a general method to obtain three
      dimensional structures of many filamentous biological macromolecules. The method
      assumes helical symmetry, and generates the three-dimensional structures from two
      dimensional projection images. However, the theory is inadequate to describe
      filamentous structures discontinuities, which are called seams in the case of
      microtubules or perturbations in the case of tobacco mosaic virus or the
      bacterial flagellar filament. To study such structures, a new theory and
      algorithm are required. To this aim, we developed a new algorithm, namely,
      asymmetric helical reconstruction, which is based on our new theory that
      describes a "helical" object with a seam. In the theory, "helical" objects with a
      seam are indexed with a non-integral order of nu. Like the conventional helical
      reconstruction, the layer-line data are extracted from the Fourier transform of
      the images. We show that the Fourier-Bessel transform using the Bessel functions
      of fractional order can, to good approximation, reconstruct the three-dimensional
      structure of the object. To test the new algorithm, we reconstructed three
      dimensional structures of a kinesin-microtubule complex with a seam from both
      model data and experimental data from cryo-electron microscopic images. The
      reconstructed structures are almost identical with those reconstructed from
      conventional helical reconstruction demonstrating the validity of the algorithm.
      The algorithm enables the analysis of various "helical" specimens with seams and
      also significantly improves the throughput and the resolution of kinesin
      microtubule complexes.

PMID- 15476813
TI  - Growth-regulatory human galectin-1: crystallographic characterisation of the
      structural changes induced by single-site mutations and their impact on the
      thermodynamics of ligand binding.
AB  - Human galectin-1 is a potent multifunctional effector that participates in
      specific protein-carbohydrate and protein-protein (lipid) interactions. By
      determining its X-ray structure, we provide the basis to define the structure of
      its ligand-binding pocket and to perform rational drug design. We have also
      analysed whether single-site mutations introduced at some distance from the
      carbohydrate recognition domain can affect the lectin fold and influence sugar
      binding. Both the substitutions introduced in the C2S and R111H mutants altered
      the presentation of the loop, harbouring Asp123 in the common "jelly-roll" fold.
      The orientation of the side-chain was inverted 180 degrees and the positions of
      two key residues in the sugar-binding site of the R111H mutant were notably
      shifted, i.e. His52 and Trp68. Titration calorimetry was used to define the
      decrease in ligand affinity in both mutants and a significant increase in the
      entropic penalty was found to outweigh a slight enhancement of the enthalpic
      contribution. The position of the SH-groups in the galectin appeared to
      considerably restrict the potential to form intramolecular disulphide bridges and
      was assumed to be the reason for the unstable lectin activity in the absence of
      reducing agent. However, this offers no obvious explanation for the improved
      stability of the C2S mutant under oxidative conditions. The noted long-range
      effects in single-site mutants are relevant for the functional divergence of
      closely related galectins and in more general terms, the functionality definition
      of distinct amino acids.

PMID- 15476814
TI  - The DxDxDG motif for calcium binding: multiple structural contexts and
      implications for evolution.
AB  - Calcium ions regulate many cellular processes and have important structural roles
      in living organisms. Despite the great variety of calcium-binding proteins
      (CaBPs), many of them contain the same Ca(2+)-binding helix-loop-helix structure,
      referred to as the EF-hand. In the canonical EF-hand, the loop contains three
      calcium-binding aspartic acid residues, which form the DxDxDG sequence motif, and
      is flanked by two alpha-helices. Recently, other CaBPs containing the same motif,
      but lacking one or both helices, have been described. Here, structural motif
      searches were used to analyse the full diversity of structural context in the
      known set of DxDxDG-containing CaBPs, including those where the structural
      resemblance of a given DxDxDG motif to that of EF-hands had not been noted. The
      results obtained indicate that the EF-hand represents but one, among many,
      structural context for the DxDxDG-like Ca(2+)-binding loops. While the structural
      similarity of the binuclear calcium-binding sites in anthrax protective antigen
      and human thrombospondin suggests that they are homologous, evolutionary
      relationships for mononuclear sites are harder to discern. The possible scenarios
      for the evolution of DxDxDG motif-containing calcium-binding loops in a variety
      of non-homologous proteins suggested loop transplant as a mechanism perhaps
      responsible for much of the diversity in structural contexts of present day
      DxDxDG-type CaBPs. Additionally, while it can be shown that existence of a DxDxDG
      sequence is not enough to confer a conformation suitable for calcium binding,
      local convergent evolution may still have a role. The analysis presented here has
      consequences for the prediction of calcium binding from sequence alone.

PMID- 15476815
TI  - Multivalent scFv display of phagemid repertoires for the selection of
      carbohydrate-specific antibodies and its application to the Thomsen-Friedenreich
      antigen.
AB  - The Thomsen-Friedenreich disaccharide (TF) is a promising target antigen for
      tumor immunotherapy, since it is almost exclusively expressed in carcinoma
      tissues. The TF-specific antibodies generated so far are IgMs of mouse origin
      with limited therapeutic potential. Phage-displayed scFv repertoires are an
      established source for recombinant antibodies; however, we were unable to
      identify scFvs binding to TF when applying libraries in the standard monovalent
      display format of phagemid systems. Here, we report on the successful selection
      of TF-specific antibody fragments using a multivalent scFv phagemid library
      format based on shortened linkers (one amino acid residue). The libraries were
      constructed from mice immunized with asialoglycophorin and selected using TF
      displayed on two different carrier molecules in combination with the
      proteolytically cleavable helper phage KM13. All isolated clones encoded the same
      framework genes and the same complementarity-determining regions. After affinity
      maturation only scFv with the founder sequence were selected from secondary
      repertoires. This indicates a very narrow sequence window for TF-specific
      antibodies. Investigating other linker-length formats revealed a clear inverse
      correlation between linker length and binding activity both as soluble proteins
      and displayed on phages. The highest affinity was obtained with the tetrameric
      format. The selected scFv was specific for TF on various carrier molecules and
      tumor cells and performed well in ELISA and immunohistochemistry. We postulate
      that scFv phagemid library formats with short linkers (i.e. multimeric scFvs)
      may, in general, be advantageous in selections for the generation of scFvs
      against carbohydrate epitopes or other epitopes associated with low intrinsic
      affinity per binding site), and expect that they will be superior in applications
      for diagnosis or therapy.

PMID- 15476816
TI  - Plasmin(ogen)-binding alpha-enolase from Streptococcus pneumoniae: crystal
      structure and evaluation of plasmin(ogen)-binding sites.
AB  - Alpha-enolases are ubiquitous cytoplasmic, glycolytic enzymes. In pathogenic
      bacteria, alpha-enolase doubles as a surface-displayed plasmin(ogen)-binder
      supporting virulence. The plasmin(ogen)-binding site was initially traced to the
      two C-terminal lysine residues. More recently, an internal nine-amino acid motif
      comprising residues 248 to 256 was identified with this function. We report the
      crystal structure of alpha-enolase from Streptococcus pneumoniae at 2.0A
      resolution, the first structure both of a plasminogen-binding and of an octameric
      alpha-enolase. While the dimer is structurally similar to other alpha-enolases,
      the octamer places the C-terminal lysine residues in an inaccessible, inter-dimer
      groove restricting the C-terminal lysine residues to a role in folding and
      oligomerization. The nine residue plasminogen-binding motif, by contrast, is
      exposed on the octamer surface revealing this as the primary site of interaction
      between alpha-enolase and plasminogen.

PMID- 15476817
TI  - Crystal structure of S-adenosyl-L-homocysteine hydrolase from the human malaria
      parasite Plasmodium falciparum.
AB  - The human malaria parasite Plasmodium falciparum is responsible for the death of
      more than a million people each year. The emergence of strains of malarial
      parasite resistant to conventional drug therapy has stimulated searches for
      antimalarials with novel modes of action. S-Adenosyl-L-homocysteine hydrolase
      (SAHH) is a regulator of biological methylations. Inhibitors of SAHH affect the
      methylation status of nucleic acids, proteins, and small molecules. P.falciparum
      SAHH (PfSAHH) inhibitors are expected to provide a new type of chemotherapeutic
      agent against malaria. Despite the pressing need to develop selective PfSAHH
      inhibitors as therapeutic drugs, only the mammalian SAHH structures are currently
      available. Here, we report the crystal structure of PfSAHH complexed with the
      reaction product adenosine (Ado). Knowledge of the structure of the Ado complex
      in combination with a structural comparison with Homo sapiens SAHH (HsSAHH)
      revealed that a single substitution between the PfSAHH (Cys59) and HsSAHH (Thr60)
      accounts for the differential interactions with nucleoside inhibitors. To examine
      roles of the Cys59 in the interactions with nucleoside inhibitors, a mutant
      PfSAHH was prepared. A replacement of Cys59 by Thr results in mutant PfSAHH,
      which shows HsSAHH-like nucleoside inhibitor sensitivity. The present structure
      should provide opportunities to design potent and selective PfSAHH inhibitors.

PMID- 15476818
TI  - Analysis of the class I aldolase binding site architecture based on the crystal
      structure of 2-deoxyribose-5-phosphate aldolase at 0.99A resolution.
AB  - The crystal structure of the bacterial (Escherichia coli) class I 2-deoxyribose-5
      phosphate aldolase (DERA) has been determined by Se-Met multiple anomalous
      dispersion (MAD) methods at 0.99A resolution. This structure represents the
      highest-resolution X-ray structure of an aldolase determined to date and enables
      a true atomic view of the enzyme. The crystal structure shows the ubiquitous TIM
      alpha/beta barrel fold. The enzyme contains two lysine residues in the active
      site. Lys167 forms the Schiff base intermediate, whereas Lys201, which is in
      close vicinity to the reactive lysine residue, is responsible for the perturbed
      pK(a) of Lys167 and, hence, also a key residue in the reaction mechanism. DERA is
      the only known aldolase that is able to use aldehydes as both aldol donor and
      acceptor molecules in the aldol reaction and is, therefore, of particular
      interest as a biocatalyst in synthetic organic chemistry. The uncomplexed DERA
      structure enables a detailed comparison with the substrate complexes and
      highlights a conformational change in the phosphate-binding site. Knowledge of
      the enzyme active-site environment has been the basis for exploration of
      catalysis of non-natural substrates and of mutagenesis of the phosphate-binding
      site to expand substrate specificity. Detailed comparison with other class I
      aldolase enzymes and DERA enzymes from different organisms reveals a similar
      geometric arrangement of key residues and implies a potential role for water as a
      general base in the catalytic mechanism.

PMID- 15476819
TI  - Solution structure of the Escherichia coli YojN histidine-phosphotransferase
      domain and its interaction with cognate phosphoryl receiver domains.
AB  - The Rcs signaling system in Escherichia coli controls a variety of physiological
      functions, including capsule synthesis, cell division and motility. The activity
      of the central regulator RcsB is modulated by phosphorylation through the sensor
      kinases YojN and RcsC, with the YojN histidine phosphotransferase (HPt) domain
      representing the catalytic unit that coordinates the potentially reversible
      phosphotransfer reaction between the receiver domains of the RcsB and RcsC
      proteins. Heteronuclear high-resolution NMR spectroscopy was employed to
      determine the solution structure of the YojN-HPt domain and to map the
      interaction with its two cognate receiver domains. The solution structure of YojN
      HPt exhibits a well-ordered and rigid protein core consisting of the five helices
      alphaI to alphaV. The helices alphaII to alphaV form a four-helix bundle
      signature motif common to proteins of similar function, and helix alphaI forms a
      cap on top of the bundle. The helix alphaII is separated by a proline induced
      kink into two parts with different orientations and dynamic behavior that is
      potentially important for complex formation with other proteins. The N-terminal
      part of YojN-HPt spanning the first 26 amino acid residues seems to contain
      neither a regular secondary structure nor a stable tertiary structure and is
      disordered in solution. The identified YojN-HPt recognition sites for the
      regulator RcsB and for the isolated receiver domain of the RcsC kinase largely
      overlap in defined regions of the helices alphaII and alphaIII, but show
      significant differences. Using the residues with the largest chemical shift
      changes obtained from titration experiments, we observed a dissociation constant
      of approximately 200microM for YojN-HPt/RcsC-PR and of 40microM for YojN-HPt/RcsB
      complexes. Our data indicate the presence of a recognition area in close vicinity
      to the active-site histidine residue of HPt domains as a determinant of
      specificity in signal-transduction pathways.

PMID- 15476820
TI  - Activation of calpain by Ca2+: roles of the large subunit N-terminal and domain
      III-IV linker peptides.
AB  - The calpains are a family of cysteine proteases with closely related amino acid
      sequences, but a wide range of Ca(2+) requirements (K(d)). For m-calpain, K(d) is
      approximately 325microM, for mu-calpain it is approximately 50microM, and for
      calpain 3 it is not strictly known but may be approximately 0.1microM. On the
      basis of previous structure determination of m-calpain we postulated that two
      regions of the calpain large subunits, the N-terminal peptide (residues 1-20) and
      a domain III-IV linker peptide (residues 514-530 in m-calpain) were important in
      defining K(d). The mutations Lys10Thr in the N-terminal peptide, and Glu517Pro in
      the domain linker peptide, reduced K(d) of m-calpain by 30% and 42%,
      respectively, revealing that these two regions are functionally important. The
      increased Ca(2+)-sensitivity of these mutants demonstrate that the Lys10-Asp148
      salt link and the short beta-sheet interaction involving Glu517 are factors
      contributing to the high K(d) of m-calpain. Though these two regions are
      physically remote from the active site and Ca(2+)-binding site, they play
      significant roles in regulating the response of calpain to Ca(2+). Differences in
      these interactions in mu-calpain and in calpain 3 are also consistent with their
      progressively lower K(d) values.

PMID- 15476821
TI  - Structure of a human A-type potassium channel interacting protein DPPX, a member
      of the dipeptidyl aminopeptidase family.
AB  - It has recently been reported that dipeptidyl aminopeptidase X (DPPX) interacts
      with the voltage-gated potassium channel Kv4 and that co-expression of DPPX
      together with Kv4 pore forming alpha-subunits, and potassium channel interacting
      proteins (KChIPs), reconstitutes properties of native A-type potassium channels
      in vitro. Here we report the X-ray crystal structure of the extracellular domain
      of human DPPX determined at 3.0A resolution. This structure reveals the potential
      for a surface electrostatic change based on the protonation state of histidine.
      Subtle changes in extracellular pH might modulate the interaction of DPPX with
      Kv4.2 and possibly with other proteins. We propose models of DPPX interaction
      with the voltage-gated potassium channel complex. The dimeric structure of DPPX
      is highly homologous to the related protein DPP-IV. Comparison of the active
      sites of DPPX and DPP-IV reveals loss of the catalytic serine residue but the
      presence of an additional serine near the "active" site. However, the arrangement
      of residues is inconsistent with that of canonical serine proteases and DPPX is
      unlikely to function as a protease (dipeptidyl aminopeptidase).

PMID- 15476822
TI  - Crystal structure of the human lamin A coil 2B dimer: implications for the head
      to-tail association of nuclear lamins.
AB  - Nuclear intermediate filaments (IFs) are made from fibrous proteins termed lamins
      that assemble, in association with several transmembrane proteins of the inner
      nuclear membrane and an unknown number of chromatin proteins, into a filamentous
      scaffold called the nuclear lamina. In man, three types of lamins with
      significant sequence identity, i.e. lamin A/C, lamin B1 and B2, are expressed.
      The molecular characteristics of the filaments they form and the details of the
      assembly mechanism are still largely unknown. Here we report the crystal
      structure of the coiled-coil dimer from the second half of coil 2 from human
      lamin A at 2.2A resolution. Comparison to the recently solved structure of the
      homologous segment of human vimentin reveals a similar overall structure but a
      different distribution of charged residues and a different pattern of intra- and
      interhelical salt bridges. These features may explain, at least in part, the
      differences observed between the lamin and vimentin assembly pathways. Employing
      a modeled lamin A coil 1A dimer, we propose that the head-to-tail association of
      two lamin dimers involves strong electrostatic attractions of distinct clusters
      of negative charge located on the opposite ends of the rod domain with arginine
      clusters in the head domain and the first segment of the tail domain. Moreover,
      lamin A mutations, including several in coil 2B, have been associated with human
      laminopathies. Based on our data most of these mutations are unlikely to alter
      the structure of the dimer but may affect essential molecular interactions
      occurring in later stages of filament assembly and lamina formation.

PMID- 15476823
TI  - ZZ domain of CBP: an unusual zinc finger fold in a protein interaction module.
AB  - CREB-binding protein (CBP) is a large, multi-domain protein that provides a
      multitude of binding sites for transcriptional coactivators. The site of
      interaction of the tumor suppressor p53 and the oncoprotein E1A with CBP/p300 has
      been identified with the third cysteine-histidine-rich (CH3) domain, which
      incorporates two zinc-binding motifs, ZZ and TAZ2. We show that these two domains
      fold independently and do not interact in solution. Our experiments demonstrate
      conclusively that the interaction of p53 and E1A with the CH3 domain resides
      exclusively in the TAZ2 domain, with no contribution from the ZZ domain. We
      report also the three-dimensional solution structure of the ZZ domain of murine
      CBP. The 52 residue ZZ domain contains two twisted antiparallel beta-sheets and a
      short alpha-helix, and binds two zinc ions. The identity of the zinc coordinating
      ligands was resolved unambiguously using NMR spectroscopy of the ZZ domain
      substituted with (113)Cd. One zinc ion is coordinated tetrahedrally via two CXXC
      motifs to four cysteine side-chains, and the second zinc ion is coordinated
      tetrahedrally by a third CXXC motif, together with an unusual HXH motif
      coordinating via the N(epsilon2) atom of His40 and the N(delta1) atom of His-42.
      The first zinc cluster of the ZZ domain is strictly conserved, whereas the second
      zinc cluster shows variability in the position of the two histidine residues,
      reflecting the wide variety of molecules that incorporate ZZ domains. The
      structure of the ZZ domain shows that it belongs to the family of cross-brace
      zinc finger motifs that include the PHD, RING, and FYVE domains; however, its
      biological function is unclear. Mapping of the positions of conserved residues
      onto the calculated structures reveals a face containing exposed aromatic and
      hydrophobic side-chains, while the opposite face contains a series of conserved
      charged or hydrophilic groups. These homologies suggest that the ZZ domain is
      involved in ligand binding or molecular scaffolding, with specificity provided by
      the variability of the sequence that contains the helix in the murine CPB ZZ
      domain structure.

PMID- 15476824
TI  - Protein misfolding: optional barriers, misfolded intermediates, and pathway
      heterogeneity.
AB  - To investigate the character and role of misfolded intermediates in protein
      folding, a recombinant cytochrome c without the normally blocking histidine to
      heme misligation was studied. Folding remains heterogeneous as in the wild-type
      protein. Half of the population folds relatively rapidly to the native state in a
      two-state manner. The other half collapses (fluorescence quenching) and forms a
      full complement of helix (CD) with the same rate and denaturant dependence as the
      fast folding fraction but then is blocked and reaches the native structure (695nm
      absorbance) much more slowly. The factors that transiently block folding are not
      intrinsic to the folding process but depend on ambient conditions, including
      protein aggregation (f(concentration)), N terminus to heme misligation (f(pH)),
      and proline mis-isomerization (f(U state equilibration time)). The misfolded
      intermediate populated by the slowly folding fraction was characterized by
      hydrogen exchange pulse labeling. It is very advanced with all of the native-like
      elements fairly stably formed but not the final Met80-S to heme iron ligation,
      similar to a previously studied molten globule form induced by low pH. To
      complete final native state acquisition, some small back unfolding is required
      (error repair) but the misfolded intermediate does not revisit the U state before
      proceeding to N. These properties show that the intermediate is a normal on
      pathway form that contains, in addition, adventitious misfolding errors that
      transiently block its forward progress. Related observations for other proteins
      (partially misfolded intermediates, pathway heterogeneity) might be similarly
      explained in terms of the optional insertion of error-dependent barriers into a
      classical folding pathway.

PMID- 15476826
TI  - Water as a conformational editor in protein folding.
AB  - As molecules approach one another in aqueous solution, desolvation free energy
      barriers to association are encountered. Experiments suggest these (de)solvation
      effects contribute to the free energy barriers separating the folded and unfolded
      states of protein molecules. To explore their influence on the energy landscapes
      of protein folding reactions, we have incorporated desolvation barriers into a
      semi-realistic, off-lattice protein model that uses a simplified physico-chemical
      force-field determined solely by the sequence of amino acids. Monte Carlo
      sampling techniques were used to study the effects on the thermodynamics and
      kinetics of folding of a number of systems, diverse in structure and sequence. In
      each case, desolvation barriers increase the stability of the native conformation
      and the cooperativity of the major folding/unfolding transition. The folding
      times of these systems are reduced significantly upon inclusion of desolvation
      barriers, demonstrating that the particulate nature of the solvent engenders a
      more defined route to the native fold.

PMID- 15476825
TI  - Comparison of the transition states for folding of two Ig-like proteins from
      different superfamilies.
AB  - In the "fold approach" proteins with a similar fold but different sequences are
      compared in order to investigate the relationship between native state structure
      and folding behaviour. Here we compare the properties of the transition states
      for folding of TI I27, the 27th immunoglobulin domain from human cardiac titin,
      and that of TNfn3, the third fibronectin type III domain from human tenascin.
      Experimental phi-values were used as restraints in molecular dynamics simulations
      to determine the structures that make up the transition state ensembles (TSEs)
      for folding of the two proteins. The restrained simulations that we present allow
      a detailed structural comparison of the two TSEs to be made. Further calculations
      show explicitly that for both proteins the formation of the interactions
      involving the residues in the folding nucleus is sufficient for the establishment
      of the topology of the Ig-like fold. We found that, although the folding nuclei
      of the two proteins are similar, the packing of the folding nucleus of TI I27 is
      much tighter than that of TNfn3, reflecting the higher experimental phi-values
      and beta(T) (Tanford Beta) of TI I27. These results suggest that the folding
      nucleus can be significantly deformed to accommodate extensive sequence variation
      while conserving the same folding mechanism.

PMID- 15476827
TI  - Multiple domains of Ruk/CIN85/SETA/CD2BP3 are involved in interaction with
      p85alpha regulatory subunit of PI 3-kinase.
AB  - Ruk/CIN85/SETA/CD2BP3 and CD2AP/CMS/METS-1 comprise a new family of proteins
      involved in such fundamental processes as clustering of receptors and
      rearrangement of the cytoskeleton in regions of specialised cell-cell contacts,
      ligand-activated internalisation and targeting to lysosome degradation pathway of
      receptor tyrosine kinases, and apoptotic cell death. As typical adapter proteins
      they execute these functions by interacting with other signalling molecules via
      multiple protein-protein interaction interfaces: SH3 domains, Pro-rich region and
      coiled-coil domain. It has been previously demonstrated that Ruk is able to
      interact with the p85alpha regulatory subunit of PI 3-kinase and that the SH3
      domain of p85alpha is required for this interaction. However, later observations
      hinted at a more complex mechanism than simple one-way SH3-Pro-rich interaction.
      Because interaction with p85alpha was suggested to be important for pro-apoptotic
      activity of the long isoform of Ruk, Ruk(l)/CIN85, we carried out detailed
      studies of the mechanism of this interaction and demonstrated that multiple
      domains are involved; SH3 domains of Ruk are required and sufficient for
      efficient interaction with full-length p85alpha but the SH3 domain of p85alpha is
      vital for their "activation" by ousting them from intramolecular interaction with
      the Pro-rich region of Ruk. Our data also suggest that homodimerisation via C
      terminal coiled-coil domain affects both intra- and intermolecular interactions
      of Ruk proteins.

PMID- 15476829
TI  - The value of legislated conservation?

PMID- 15476828
TI  - Molecular basis of distinct interactions between Dok1 PTB domain and tyrosine
      phosphorylated EGF receptor.
AB  - Phosphotyrosine binding (PTB) domains of the adaptor proteins Doks (downstream of
      tyrosine kinases) play an important role in regulating signal transduction of
      cell-surface receptors in cell growth, proliferation and differentiation;
      however, ligand specificity of the Dok PTB domains has until now remained
      elusive. In this study, we have investigated the molecular basis of specific
      association between the Dok1 PTB domain and the tyrosine-phosphorylated EGFR.
      Using yeast two-hybrid and biochemical binding assays, we show that only the PTB
      domain from Dok1 but not Dok4 or Dok5 can selectively bind to two known tyrosine
      phosphorylation sites at Y1086 and Y1148 in EGFR. Our structure-based mutational
      analyses define the molecular determinants for the two distinct Dok1 PTB
      domain/EGFR interactions and provide the structural understanding of the specific
      interactions between EGFR and PTB domains in the divergent Dok homologues.

PMID- 15476830
TI  - The mixed value of environmental regulations: do acroporid corals deserve
      endangered species status?

PMID- 15476831
TI  - The potential listing of Acropora species under the US Endangered Species Act.

PMID- 15476832
TI  - Ecosystem history of Mississippi River-influenced continental shelf revealed
      through preserved phytoplankton pigments.
AB  - Pigments determined by high performance liquid chromatography (HPLC) provide
      useful information concerning water column and epibenthic plant and microbial
      communities in both extant communities and accumulated sediments in lakes,
      estuaries and the ocean. Chlorophyll and its degradation products provide an
      estimate of overall biomass, and carotenoid pigments provide taxonomic biomarkers
      of phytoplankton. We examined the pigments preserved in sediment cores from the
      Louisiana continental shelf adjacent to the outflow of the Mississippi River
      system to document changes in phytoplankton community composition, phytoplankton
      abundance, and conditions of hypoxia over time. Carbon accumulated in sediments
      from water depths of 20-60 m is primarily derived from marine phytoplankton and
      represents the history of phytoplankton communities in the overlying water. There
      is a general increase in chlorophyll a, pheopigments, zeaxanthin, fucoxanthin and
      most carotenoids over time, with the change gradual from 1955 to 1970, followed
      by a fairly steady increase to 1997. The highest chloropigment concentrations are
      in cores from areas more likely to be exposed to seasonal hypoxia. These indicate
      an increase in eutrophication in the form of greater diatom and cyanobacterial
      production, or a worsening of hypoxia, or both. This trend expanded westward
      along the Louisiana shelf in the 1990s.

PMID- 15476833
TI  - A retrospective analysis of trace metals, C, N and diatom remnants in sediments
      from the Mississippi River delta shelf.
AB  - The development of oil and gas recovery offshore of the Mississippi River delta
      began in shallow water in the 1950s, expanded into deeper waters, and peaked in
      the 1990s. This area of the outer continental shelf (OCS) is the historical and
      present location of >90% of all US OCS oil and gas production and reserves. The
      juxtaposition of its 4000 producing platforms, recovering $10 billion yr(-1) of
      oil, gas and produced water in the same area where about 28% of the US fisheries
      catch (by weight) is made and near 40% of the US coastal wetlands, makes this an
      area worth monitoring for regional pollutant loading. This loading may come from
      several sources, including sources related to OCS development, but also from the
      Mississippi River watershed. In this context, any contaminant loading on this
      shelf may be neither detectable nor significant against a background of climatic
      or biological variability. We examined the sedimentary record for indicators of
      industrial byproducts from OCS oil and gas development and of industrial products
      entering via the Mississippi River, primarily using vanadium (V) and barium (Ba)
      concentrations normalized for aluminum (Al). Barium is primarily used in drilling
      muds in the form of barite, whereas V is an important strengthening component of
      metal alloys, including steel. The fluctuations in the accumulation of Ba, but
      not V, were coincidental with the presumed use of barite. The fluctuations in V
      concentration in the sediments were coincidental with the national consumption of
      V. Copper (Cu), cadmium (Cd) and zinc (Zn) concentrations in sediments fluctuate
      coincidentally with V, not Ba, thus indicating that the dominant source of these
      trace metals in offshore sediments were derived from riverine sources, and were
      not primarily from in situ industrial processes releasing them on the shelf. This
      is not to suggest that local site-specific contamination is not a significant
      management or health concern. The low oxygen (hypoxia; < or = 2 mg l(-1)) zone
      that consistently covers much of this continental shelf's bottom layer in summer
      is attributed to nitrate loading from the Mississippi River. Increased nitrogen
      loading from river to shelf stimulates diatom production whose loading to the
      bottom layer and subsequent metabolism results in oxygen being depleted faster
      than it is replaced. In the last two decades there has been an increased
      accumulation of organic matter in sediments near the mouth of the Mississippi
      River. This coupling between river water, surface water and bottom water has
      recently expanded westward of the Atchafalaya River delta towards the Texas
      coast. The accumulation of biogenic silica (BSi) and carbon in dated sediments is
      coincidental with variations in riverine nitrate flux, but not with either V or
      Ba accumulation rates. These analyses indicate that both OCS development and
      riverine sources exert strong influences on the sediment constituents offshore,
      and that these influences may be independent of one another.

PMID- 15476834
TI  - Historical polycyclic aromatic and petrogenic hydrocarbon loading in Northern
      Central Gulf of Mexico shelf sediments.
AB  - The distribution of selected hydrocarbons within ten dated sediment cores taken
      from the Mississippi River Bight off coastal Louisiana suggests a chronic
      contaminant loading from several sources including the river itself, oil and gas
      exploration in the central Gulf of Mexico (GOM) shelf area, and natural geologic
      hydrocarbon seeps. Data were grouped as either total polycyclic aromatic
      hydrocarbons (PAH's), which were indicative of pyrogenic PAH's; or estimated
      total hopanes (indicative of petrogenic hydrocarbons). The total PAH
      concentrations and estimated total hopanes begin increasing above background
      levels (approximately 200 ng g(-1)) after the 1950s. The distribution of these
      hydrocarbons and hopanes within the dated sediment cores suggests that the
      Mississippi River is a regional source of pyrogenic PAH's, and that the hopanes
      are from natural geologic hydrocarbon seeps, oil and gas exploration in the GOM,
      or both.

PMID- 15476835
TI  - Effects of tributyltin (TBT) on the seagrass Ruppia maritima.
AB  - The effects of tributyltin (TBT) on the seagrass Ruppia maritima were studied in
      two growth experiments. Plants were sampled at stations in Odense Fjord and
      Lunkebugten, Denmark, and replanted in reference sediment without TBT, reference
      sediment spiked with TBT, and in impacted sediment sampled in the highly TBT
      contaminated (7-57 microg kg (-1) dw) Odense Fjord. Plant performance was studied
      at weekly intervals for 3-4 weeks, by measuring net photosynthetic activity,
      respiration, relative growth rate (RGR) and number of leaves. Net photosynthetic
      activity in plants from spiked and impacted sediment was reduced by up to 60%
      relative to reference plants. Respiration both increased and decreased in
      response to TBT exposure, while RGR was generally lower in plants from
      contaminated sediments (reduced by 8-25%). The effects of spiked and impacted
      sediment differed between the experiments, which could be partly explained by the
      bioavailability of TBT in the two treatments, but also by adaptation of the
      plants from Odense Fjord to TBT. Measurements of enhanced TBT concentrations in
      the sediments in Odense Fjord suggest an impact of TBT on R. maritima is possible
      under in situ conditions.

PMID- 15476836
TI  - Concentration and subcellular distribution of trace elements in liver of small
      cetaceans incidentally caught along the Brazilian coast.
AB  - Concentrations of trace elements (V, Cr, Mn, Fe, Co, Cu, Zn, Ga, As, Se, Rb, Sr,
      Mo, Ag, Cd, Sb, Cs, Ba, T-Hg, Org-Hg, Tl and Pb) were determined in liver samples
      of estuarine dolphin (Sotalia guianensis; n = 20), Franciscana dolphin
      (Pontoporia blainvillei; n = 23), Atlantic spotted dolphin (Stenella frontalis; n
      = 2), common dolphin (Delphinus capensis; n = 1) and striped dolphin (Stenella
      coeruleoalba; n = 1) incidentally caught along the coast of Sao Paulo State and
      Parana State, Brazil, from 1997 to 1999. The hepatic concentrations of trace
      elements in the Brazilian cetaceans were comparable to the data available in
      literature on marine mammals from Northern Hemisphere. Concentrations of V, Se,
      Mo, Cd, T-Hg and Org-Hg increased with increasing age in liver of both estuarine
      and Franciscana dolphins. Very high concentrations of Cu (range, 262-1970
      microg/g dry wt.) and Zn (range, 242-369 microg/g dry wt.) were observed in liver
      of sucklings of estuarine dolphin. Hepatic concentrations of V, Se, T-Hg, Org-Hg
      and Pb were significantly higher in estuarine dolphin, whereas Franciscana
      dolphin showed higher concentrations of Mn, Co, As and Rb. Ratio of Org-Hg to T
      Hg in liver was significantly higher in Franciscana dolphin than estuarine
      dolphin, suggesting that demethylation ability of methyl Hg might be lower in
      liver of Franciscana than estuarine dolphins. High hepatic concentrations of Ag
      were found in some specimens of Franciscana dolphin (maximum, 20 microg/g dry
      wt.), and 17% of Franciscana showed higher concentrations of Ag than Hg. These
      samples with high Ag concentration also exhibited elevated hepatic Se
      concentration, implying that Ag might be detoxified by Se in the liver. Higher
      correlation coefficient between (Hg+0.5 Ag) and Se than between Hg and Se and the
      large distribution of Ag in non-soluble fraction in nuclear and mitochondrial
      fraction of the liver also suggests that Ag might be detoxified by Se via
      formation of Ag2Se in the liver of Franciscana dolphin.

PMID- 15476837
TI  - Species diversity and distribution for phytoplankton of the Pearl River estuary
      during rainy and dry seasons.
AB  - Based on data collected at 31 stations and 1 continuous station in the Pearl
      River estuary during cruises of July 1999 (rainy season) and January 2001 (dry
      season), this study examined taxonomic composition, abundance, and spatial
      distribution of phytoplankton. Results indicated 130 species of phytoplankton in
      the samples from the rainy season, and 132 species in the dry season. Among them,
      in the rainy season, 82 species of diatom, 39 fresh-water and half-fresh-water
      species and 41 species of red tide organisms were found. Within these, there were
      54 tropical and sub-tropical species, 47 cosmopolitan species and 17 temperate
      species. The abundance of phytoplankton in the rainy season was higher than that
      of the dry season, with an average of 6.3 x 10(5) cells x L(-1) and 1.4 x 10(5)
      cells x L(-1), respectively. Diversity index (H') and evenness (J) were 2.47 and
      0.57 in the rainy season, and 2.01 and 0.54 in the dry season. The dominant
      phytoplankton species in the rainy season was Skeletonema costatum with an
      average of 2.8 x 10(5) cells x L(-1) and 45.0% of the total phytoplankton
      abundance. In the dry season, Eucampia zoodiacus became the key dominant species
      (5.9 x 10(4) cells x L(-1)) when it was 43.47% of the total phytoplankton
      abundance. Distribution of the dominant species varied with salinity of sea
      water, and their amounts correlated negatively with nutrients and zooplankton.

PMID- 15476838
TI  - Organochlorine concentrations in various fish from different locations at Karachi
      Coast.

PMID- 15476839
TI  - Natural turbidity variability and weather forecasts in risk management of
      anthropogenic sediment discharge near sensitive environments.
AB  - Coastal development activities can cause local increases in turbidity and
      sedimentation. This study characterises the spatial and temporal variability of
      turbidity near an inshore fringing coral reef in the central Great Barrier Reef,
      under a wide range of natural conditions. Based on the observed natural
      variability, we outline a risk management scheme to minimise the impact of
      construction-related turbidity increases. Comparison of control and impact sites
      proved unusable for real-time management of turbidity risks. Instead, we suggest
      using one standard deviation from ambient conditions as a possible conservative
      upper limit of an acceptable projected increase in turbidity. In addition, the
      use of regional weather forecast as a proxy for natural turbidity is assessed.
      This approach is simple and cheap but also has limitations in very rough
      conditions, when an anthropogenic turbidity increase could prove fatal to corals
      that are already stressed under natural conditions.

PMID- 15476840
TI  - A particle-tracking model for simulating pollutant dispersion in the Strait of
      Gibraltar.
AB  - A particle-tracking model to simulate the dispersion of contaminants in the
      Strait of Gibraltar has been developed. The model solves the hydrodynamic
      equations off-line and tidal analysis is carried out to determine tidal constants
      for the two main constituents. Tidal constants and residuals are stored in files
      that are read by the dispersion model. A lagrangian approach is used to solve
      dispersion; diffusion and decay are simulated by a Monte Carlo method. A method
      for assessing the areas of the Strait with higher probability of being affected
      by contamination occurring after an accident in the shipping routes is given.
      Generally speaking, the fate of a pollutant discharge strongly depends on wind
      conditions. Winds from the east tend to retain contamination into the Strait. As
      a consequence, transverse mixing occurs and both Spain and Morocco coasts are
      affected by contamination. Under calm conditions and west winds, contaminants are
      flushed out of the Strait faster and transverse mixing does not occur. Thus, only
      part of Morocco coast has a higher probability of being affected by
      contamination.

PMID- 15476841
TI  - Assessing Oregon's twenty-six coastal beach areas for recreational water quality
      standards.
AB  - Water samples from 26 Oregon beaches were analyzed for Escherichia coli (E. coli)
      and enterococci concentrations by the Oregon Department of Human Services (ODHS)
      Public Health Laboratory. Nine Oregon beaches exceeded US Environmental
      Protection Agency's (USEPA) single sample maximum density of 104 enterococci
      colony forming units (cfu) per 100 mL with levels ranging from 121 to 4325 most
      probable number (MPN)/100 milliliters (mL). Otter Rock at South Cove had the
      highest enterococci concentration at 4352 MPN/100 mL. The results from two Oregon
      beaches exceeded Oregon Department of Environmental Quality's (ODEQ) estuarine E.
      coli standard of 406 organisms/100 mL. Otter Rock at South Cove had the highest
      E. coli concentration at 1850 MPN/100 mL while Road's End had an E. coli density
      of 771 MPN/100 mL. Results of this study suggest that adopting USEPA's marine
      enterococci standard in lieu of the ODEQ's estuarine standard will lead to
      increased Oregon beach water standard failures.

PMID- 15476842
TI  - Evaluating Oregon's beach sites for application to United States Environmental
      Protection Agency's BEACH Act criteria.
AB  - With the passage of the Beaches Environmental Assessment and Coastal Health
      (BEACH) Act in 2000, coastal states were mandated to assess and sample coastal
      recreational waters for bacterial ambient water quality parameters. The
      assessment of beach sites required the application of federal guidelines and a
      tiered approach to delineating the beaches. Eighty-seven beach sites in Oregon
      were evaluated and ranked by use, available information, pollution threats,
      sanitary survey and monitoring data results, exposure considerations, and
      economic/development factors. This ranking resulted in 19 high priority beaches
      (tier 1), five medium priority beaches (tier 2), 23 low priority beaches, and 40
      beaches with a rank of none in Oregon.

PMID- 15476843
TI  - Petroleum hydrocarbon residues in the marine environment of Bassein-Mumbai.
AB  - The paper reports PHc contamination in water, sediment and biota of the coastal
      area of Bassein-Mumbai in relation to relatively less polluted sites (Dabhol and
      Ratnagiri) off the west coast of India. To facilitate inter-comparison three
      standards have been used though the results are reported in terms of SAM (Residue
      of Saudi Arabian Mix crude). The concentration of PHc in water off Bassein-Mumbai
      varies widely (2.9-39.2 microg l(-1)) as compared to the average baseline (2.8
      microg l(-1)) with higher values generally confined to creeks and estuaries. The
      higher concentration of PHc in the bottom water of shallow areas is attributed to
      the contribution from the sediment-associated petroleum residue. High
      concentration of PHc in the surficial sediment of inshore area Ratnagiri (107.7
      ppm, dry wt) is perhaps the remnants of an oil spill that occurred in the Bombay
      High region on May 17, 1993. The majority of values of PHc concentration in the
      surficial sediment of the Bassein-Mumbai region exceed 15 ppm (dry wt) against
      the expected background (<3 ppm, dry wt) and the trend is indicative of transfer
      of PHc loads from the inshore areas to the open-shore sediments. The PHc
      concentration of 0.8-2.6 ppm (dry wt) in sediment deposited prior to the first
      global commercial use of petroleum in core R5 represents the biogenic background.
      Based on the period of industrialisation and the horizon of PHc accumulation, a
      sedimentation rate of 0.2 and 1.0 cm y(-1) respectively is estimated for cores
      U11 and U12. Substantial increase in the concentration of PHc in sediment after
      1950 in cores T8 and T10 correlates well with the establishment of refineries on
      the western shore of the Thane Creek in 1955-1960. A minor peak in most cores in
      the top 10 cm sediment probably results from biological transfer of PHc lower
      into the sediment by benthic organisms. Excess of PHc retained in the sediment of
      the Bassein-Mumbai region over the biogenic background is estimated at 40,000 t.
      The PHc residues (1.8-10.8 ppm, wet wt) in fish caught off Bassein-Mumbai do not
      suggest bioaccumulation.

PMID- 15476844
TI  - Determination of dioxin and dioxin-like compounds in sediments from UK estuaries
      using a bio-analytical approach: chemical-activated luciferase expression (CALUX)
      assay.
AB  - The DR-CALUX assay has been utilised for the bio-analytical screening of a number
      of estuarine sediments for dioxin-like activity. Total sediment extracts (samples
      containing all extracted compounds) and cleaned-up extracts (samples with the
      most stable compounds isolated from the total extracts) were screened. The
      concentration of the stable dioxin-like compounds in the cleaned-up sediment
      extracts was between 1.0 and 106 pgTEQCALUX g(-1) dry weight. The majority of
      sediments contained levels of dioxin-like compounds that were above
      concentrations that are considered to be a low risk to aquatic organisms. The
      CALUX bio-analytical approach showed some disparity with the traditional
      analytical approach. The reasons for these differences have been identified
      tentatively: firstly, the DR-CALUX assay responds to all dioxin-like compounds,
      and secondly, it measures non-additive effects. The dioxin-like activity of
      compounds in sediment total extracts, which contain both labile and stable
      compounds, were also assessed and were six orders of magnitude higher than the
      cleaned-up samples. This suggests the vast majority of the total dioxin-like
      activity is attributable to labile compounds. Overall, the DR-CALUX assay is
      shown to be a useful tool in the assessment of dioxin-like activity in estuarine
      sediments.

PMID- 15476845
TI  - Total mercury levels in tunas from offshore waters of the Florida Atlantic coast.

PMID- 15476846
TI  - The concentrations of selected trace elements in clams, Trivela mactroidea along
      the Venezuelan coast in the state of Miranda.

PMID- 15476847
TI  - Signal transduction in cancer chemoprevention.

PMID- 15476848
TI  - Effects of tea polyphenols on signal transduction pathways related to cancer
      chemoprevention.
AB  - The inhibition of carcinogenesis by tea and tea polyphenols has been demonstrated
      in different animal models by many investigators. The mechanisms of this
      inhibitory activity have also been investigated extensively, mostly in cell
      culture systems, but no clear conclusion can be reached concerning the cancer
      preventive mechanisms in vivo. In this article, we reviewed the possible
      mechanisms, which include the inhibition of specific protein kinase activities,
      blocking receptor-mediated functions, and inhibition of proteases. These events
      may lead to cell cycle regulation, growth inhibition, enhanced apoptosis,
      inhibition of angiogenesis, and inhibition of invasion and metastases. The
      possible complications of translating results obtained in cell culture studies to
      animals and humans are discussed. It is likely that multiple signal transduction
      pathways are involved in the inhibition of carcinogenesis by tea constituents.
      The relative importance of these pathways needs to be determined in vivo.

PMID- 15476849
TI  - A cancer chemopreventive agent silibinin, targets mitogenic and survival
      signaling in prostate cancer.
AB  - There are many epigenetic variables that affect the biological responses of
      autocrine, paracrine and endocrine regulatory molecules, which determine the
      growth and development of different cancers including prostate cancer (PCA). One
      of the focuses of the current cancer chemoprevention studies is the search for
      non-toxic chemopreventive agents that inhibit mitogenic and cell survival
      signaling in cancer cells. In general, advanced stage cancer cells harbor many
      constitutively active mitogenic signaling and anti-apoptotic mechanisms, which
      make them less dependent on external growth factors as well as resistant to
      chemotherapeutic agents. In this regard, silibinin (a naturally occurring
      flavanone) has shown the pleiotropic anticancer effects in different cancer
      cells. Our extensive studies with PCA have shown that inhibition of mitogenic and
      cell survival signaling, such as epidermal growth factor receptor, insulin-like
      growth factor receptor type I and nuclear factor kappa B signaling are the most
      likely molecular targets of silibinin's efficacy in PCA. We have observed that
      silibinin inhibits prostate tumor growth in animal models without any apparent
      signs of toxicity. At the same time, silibinin is also physiologically available
      in different organs of the body including plasma and prostate, which is generally
      required for the pharmacological dosing and translational mechanistic studies of
      the compound. There are substantial amount of data to support the inhibitory
      effect of silibinin on mitogenic and cell survival signaling in PCA, which are
      reviewed in the present communication.

PMID- 15476850
TI  - Targeting signal transduction pathways by chemopreventive agents.
AB  - Cancer is a dynamic process that involves many complex factors, which may explain
      why a "magic bullet" cure for cancer has not been found. Death rates are still
      rising for many types of cancers, which possibly contributes to the increased
      interest in chemoprevention as an alternative approach to the control of cancer.
      This strategy for cancer control is based on the presumption that because cancer
      develops through a multi-step process, each step may be a prospective target for
      reversing or suppressing the process. Thus, the design and development of
      chemopreventive agents that act on specific and/or multiple molecular and
      cellular targets is gaining support as a rational approach to control cancer.
      Nutritional or dietary factors have attracted a great deal of interest because of
      their perceived ability to act as highly effective chemopreventive agents. They
      are professed as being generally safe and may have efficacy as chemopreventive
      agents by preventing or reversing premalignant lesions and/or reducing second
      primary tumor incidence. Many of these dietary compounds appear to act on
      multiple target signaling pathways. Some of the most interesting and well
      documented are resveratrol and components of tea, including EGCG, theaflavins and
      caffeine. This review will focus on recent work regarding three well-accepted
      cellular/molecular mechanisms that may at least partially explain the
      effectiveness of selected food factors, including those indicated above, as
      chemopreventive anti-promotion agents. These food compounds may act by: (1)
      inducing apoptosis in cancer cells; (2) inhibiting neoplastic transformation
      through the inhibition of AP-1 and/or NF-kappaB activation; and/or (3)
      suppressing COX-2 overexpression in cancer cells.

PMID- 15476851
TI  - Cell signaling pathways altered by natural chemopreventive agents.
AB  - Epidemiological studies have indicated a significant difference in the incidence
      of cancers among ethnic groups, who have different lifestyles and have been
      exposed to different environmental factors. It has been estimated that more than
      two-thirds of human cancers, which are contributed by mutations in multiple
      genes, could be prevented by modification of lifestyle including dietary
      modification. The consumption of fruits, soybean and vegetables has been
      associated with reduced risk of several types of cancers. The in vitro and in
      vivo studies have demonstrated that some dietary components such as isoflavones,
      indole-3-carbinol (I3C), 3,3'-diindolylmethane (DIM), curcumin, (-)
      epigallocatechin-3-gallate (EGCG), apigenin, etc., have shown inhibitory effects
      on human and animal cancers, suggesting that they may serve as chemopreventive
      agents. Experimental studies have also revealed that these components regulate
      the molecules in the cell signal transduction pathways including NF-kappaB, Akt,
      MAPK, p53, AR, and ER pathways. By modulating cell signaling pathways, these
      components, among other mechanisms, activate cell death signals and induce
      apoptosis in precancerous or cancer cells, resulting in the inhibition of cancer
      development and/or progression. This article reviews current studies regarding
      the effects of natural chemopreventive agents on cancer-related cell signaling
      pathways and provides comprehensive knowledge of the biological and molecular
      roles of chemopreventive agents in cancer cells.

PMID- 15476852
TI  - Molecular basis of chemoprevention by resveratrol: NF-kappaB and AP-1 as
      potential targets.
AB  - Recently, chemoprevention by the use of naturally occurring substances is
      considered as a priority to reduce the ever-increasing incidence of cancer. The
      intervention of multistage carcinogenesis by modulating intracellular signaling
      pathways may provide molecular basis of chemoprevention with a wide variety of
      dietary phytochemicals. Resveratrol, a red wine polyphenol, has been studied
      extensively for the chemopreventive activity in the context of its ability to
      interfere with the multistage carcinogenesis. Numerous intracellular signaling
      cascades converge with the activation of nuclear factor-kappaB (NF-kappaB) and
      activator protein-1 (AP-1), which act independently or coordinately to regulate
      expression of target genes. These ubiquitous eukaryotic transcription factors
      mediate pleiotropic effects on cellular transformation and tumor promotion. This
      review aims to update the molecular mechanisms underlying chemoprevention by
      resveratrol with special focus on its effect on cellular signaling cascades
      mediated by NF-kappaB and AP-1.

PMID- 15476853
TI  - beta-catenin-mediated signaling: a molecular target for early chemopreventive
      intervention.
AB  - Dysregulation of Wnt signaling appears to be a critical event in the formation of
      intestinal tumors and some other cancers. Accumulating data from preclinical
      studies strongly suggest that targeted disruption of beta-catenin-mediated TCF
      signaling is a promising strategy for early chemopreventive intervention,
      particularly with respect to intestinal tumorigenesis. While the search for
      potent inhibitors is just getting underway, the ability of several synthetic and
      naturally occurring agents to decrease the transcriptional activity of a
      luciferase reporter plasmid under the control of TCF-4 regulatory elements
      (pTOPFLASH) has been demonstrated already. Additional enthusiasm for this
      approach is provided by data from several groups, which indicate that sulindac,
      sulindac sulfone and indomethacin can modulate the subcellular localization of
      beta-catenin in vivo, resulting in either decreased nuclear compartmentalization
      or enhanced localization of beta-catenin to the plasma membrane. Although the
      mechanism by which agents disrupt beta-catenin-mediated TCF signaling remains to
      be elucidated, possibilities include: (1) physical inhibition of the beta
      catenin/TCF complex formation, (2) upregulation of the ubiquitin-mediated
      proteosomal degradation of beta-catenin, (3) accelerated nuclear export of beta
      catenin and (4) enhanced sequestration of beta-catenin by E-cadherin. The common
      role of beta-catenin in both Wnt signaling and cell adhesion provides a unique
      opportunity to develop chemopreventive therapies that both prevent the
      development of cancer and delay tumor progression.

PMID- 15476854
TI  - Signaling pathways in retinoid chemoprevention and treatment of cancer.
AB  - The Vitamin A metabolite, retinoic acid, has been shown to have chemopreventive
      and therapeutic activity for certain cancers such as head and neck, cervical,
      neuroblastoma and promyelocytic leukemia. Retinoic acid achieves these activities
      by inducing differentiation and/or growth arrest. A large number of studies have
      investigated the mechanism(s) by which retinoic acid alters the behavior of
      premalignant and tumor cells. Although much important data has been obtained, the
      exact signaling pathways required for retinoic acid to exert its biological
      effects remains elusive. In this review, we outline the role and function of
      retinoid nuclear receptors, followed by a discussion of how major signaling
      pathways are affected in different tumor types by retinoids. We conclude by
      examining the effect of retinoic acid on G1 cell cycle regulatory proteins in
      various tumors.

PMID- 15476855
TI  - Nitric oxide signaling in colon cancer chemoprevention.
AB  - Nitric oxide (NO) is a pleiotrophic regulator, pivotal to numerous biological
      processes, including vasodilation, neurotransmission, and macrophage-mediated
      immunity. The highly reactive free radicals, produced by NO synthases (NOS) have
      been implicated in the modulation of carcinogenesis. Over-expression of inducible
      NOS (iNOS), a common phenomenon during chronic inflammatory conditions, generates
      sustainable amounts of NO, that its reactive intermediates are mutagenic, causing
      DNA damage or impairment of DNA repair, has been well established in
      carcinogenesis. Recent studies also implicate NO as having a key signaling
      molecule that regulates processes of tumorigenesis. Increased expression of iNOS
      has been observed in tumors of the colon, lung, oropharynx, reproductive organs,
      breast, and central nervous system besides its occurrence in chronic inflammatory
      diseases. Progression of a large majority of human and experimental colon tumors
      appears to progress by NO resulting from stimulation of proinflammatory
      cytokines, and inactivation (nitrosylation) of p53 mediated caspase activities in
      the tumors, whereas in some cases it associated with induction of apoptosis and
      tumor regression. This dichotomy is largely explained by the complexity of
      signaling pathways in tumor cells, that respond to NO very differently depending
      on its concentration. p53 mutation, functional loss, activation, and inactivation
      of apoptotic proteins all have been linked with NO resistance and dependence.
      Evidence from both in vitro and in vivo experiments support that NO and its
      reactive metabolite peroxynitrite stimulate COX-2 activity leading generation of
      tumor growth enhancing prostaglandins. Thus, NO mediated signaling can augment
      the tumor growth and metastasis by promoting invasive and angiogenic properties
      of tumor cells, which includes triggering and activation of COX-2. Thus,
      developing selective inhibitors of iNOS and NO-releasing agents may lead to
      important strategies for chemoprevention of colon cancer. Chemoprevention studies
      at preclinical level with several selective inhibitors of iNOS in both chemically
      and transgenic models of colon cancer are encouraging.

PMID- 15476856
TI  - Signal transduction pathways leading to cell cycle arrest and apoptosis induction
      in cancer cells by Allium vegetable-derived organosulfur compounds: a review.
AB  - Epidemiological studies continue to support the premise that dietary intake of
      Allium vegetables (e.g., garlic, onions and so forth) may lower the risk of
      various types of cancer. Anticarcinogenic effect of Allium vegetables is
      attributed to organosulfur compounds (OSCs) that are generated upon processing of
      these vegetables. Preclinical studies have provided convincing evidence to
      indicate that Allium vegetable-derived OSCs including diallyl sulfide, diallyl
      disulfide and diallyl trisulfide are highly effective in affording protection
      against cancer in laboratory animals induced by a variety of chemical
      carcinogens. Inhibition of carcinogen activation through modulation of cytochrome
      P450-dependent monooxygenases and/or acceleration of carcinogen detoxification
      via induction of phase II enzymes (glutathione transferases, quinone reductase,
      etc.) are believed to be responsible for protective effects of OSCs against
      chemically induced cancers. More recent studies have indicated that some
      naturally occurring OSC analogues can suppress proliferation of cancer cells in
      culture and inhibit growth of transplanted tumor xenografts in vivo by inducing
      apoptosis and/or by perturbing cell cycle progression. This review summarizes
      current knowledge on signal transduction pathways leading to perturbations in
      cell cycle progression and apoptosis induction by OSCs.

PMID- 15476857
TI  - Chemoprevention through the Keap1-Nrf2 signaling pathway by phase 2 enzyme
      inducers.
AB  - One successful strategy for cancer chemoprevention is modulation of drug
      metabolizing enzymes, leading to a facilitated elimination of endogenous and
      environmental carcinogens. Inducers of phase 2 enzymes such as dithiolethiones
      inhibit tumorigenesis of environmental carcinogens in various animal models and
      modulate the metabolism of the carcinogen aflatoxin B1 in human clinical trials.
      Increasing lines of evidence show that the Keap1-Nrf2 complex is a key molecular
      target of chemopreventive phase 2 enzyme inducers. The transcription factor Nrf2
      is a member of the basic leucine-zipper NF-E2 family and interacts with the
      antioxidant response element (ARE) in the promoter region of phase 2 detoxifying
      enzymes. A cytoplasmic actin-binding protein, Keap1, is an inhibitor of Nrf2 that
      sequesters it in the cytoplasm. Inducers dissociate this complex, allowing Nrf2
      to translocate to the nucleus. Disruption of the nrf2 gene in mice leads to the
      loss of chemopreventive efficacy by inducers. This review focuses on (1) the role
      of Nrf2 in the regulation of phase 2 and antioxidative genes, (2) the molecular
      actions of dithiolethiones on the Keap1-Nrf2 pathway, and (3) the contribution of
      Nrf2-regulated gene families to the cytoprotective actions of dithiolethiones and
      other inducers. Rapidly accumulating data on this pathway is providing insight
      into the coordinated mammalian defense systems against electrophiles and
      oxidative stresses and the means by which it may be targeted by small molecules.

PMID- 15476859
TI  - Cancer-preventive isothiocyanates: measurement of human exposure and mechanism of
      action.
AB  - Numerous studies in rodents have documented the cancer-preventive activity of a
      significant number of isothiocyanates (ITCs), the majority of which occur in
      plants, especially in cruciferous vegetables. Dietary ITCs may play an important
      role in the prevention of human cancers. Several recent epidemiological studies
      have already shown that dietary consumption of ITCs inversely correlates with the
      risk of developing lung, breast and colon cancers. ITCs are principally
      metabolized through the mercapturic acid pathway in vivo, giving rise to N
      acetylcysteine conjugates, which are excreted in the urine. Analytical methods
      have been developed to allow detection of ITCs and their metabolites formed in
      the mercapturic acid pathway. Studies show that total urinary level of ITC
      equivalent is an excellent biomarker of human exposure to ITCs. Moreover, these
      methods also have made it possible to learn the bioavailability of ITCs from
      cruciferous vegetables. ITCs possess multiple anticarcinogenic mechanisms,
      including inhibition of carcinogen-activating enzymes, induction of carcinogen
      detoxifying enzymes, increase of apoptosis, arrest of cell cycle progression, as
      well as several other mechanisms that are not yet fully described. These
      mechanisms, which are discussed in detail in this review, illustrate the
      remarkable ability of ITCs to inhibit cancer development-effective against both
      developing and developed cancer cells.

PMID- 15476858
TI  - Contribution of NAD(P)H:quinone oxidoreductase 1 to protection against
      carcinogenesis, and regulation of its gene by the Nrf2 basic-region leucine
      zipper and the arylhydrocarbon receptor basic helix-loop-helix transcription
      factors.
AB  - NAD(P)H:quinone oxidoreductase 1 (NQO1) is a key enzyme involved in defence
      against reactive forms of oxygen and inhibition of neoplasia. Under conditions of
      oxidative stress, expression of NQO1 is induced, and the resulting increase in
      oxidoreductase protein provides the cell with multiple layers of protection
      against environmental insults. Firstly, the catalytic activity of NQO1 is
      directed towards the complete reduction and detoxication of highly reactive
      quinones. Secondly, the oxidoreductase maintains the endogenous lipid-soluble
      antioxidants, alpha-tocopherol-hydroquinone and ubiquinol in their reduced and
      active forms. Thirdly, NQO1 is required for the stabilisation of p53 protein in
      response to DNA-damaging stimuli, and it thereby influences cell fate decisions.
      In view of the anticarcinogenic actions of NQO1, an understanding of the
      mechanisms that govern its expression is desirable. The redox sensitivity of NQO1
      transcription occurs through a cis-acting antioxidant response element (ARE)
      located within the regulatory region of the mouse, rat and human genes. This
      element recruits the positively acting basic leucine zipper (bZip) transcription
      factor NF-E2 p45-related factor 2 (Nrf2). Under normal constitutive conditions,
      Nrf2 associates with the cytoskeletal-binding protein Keap1, which regulates the
      subcellular distribution of the bZip factor and also targets it for proteasome
      dependent degradation. Oxidative stress inhibits the Nrf2-Keap1 interaction, thus
      promoting nuclear accumulation of the transcription factor and transactivation of
      NQO1 and other ARE-driven genes. Mouse, rat and human NQO1 can also be induced by
      planar aromatic hydrocarbons through a cis-acting xenobiotic response element
      (XRE) located in their gene promoters. The XRE recruits the arylhydrocarbon
      receptor (AhR) and AhR nuclear translocator. Cross-talk may occur between Nrf2
      and AhR, but the details of this process remain to be elucidated.

PMID- 15476860
TI  - Chemoprevention by isothiocyanates and their underlying molecular signaling
      mechanisms.
AB  - Chemoprevention is a cancer preventive strategy to inhibit, delay or reverse
      carcinogenesis using naturally occurring or synthetic chemical agents. Numerous
      epidemiological studies as well as experimental animal studies clearly
      demonstrate that high intake of cruciferous vegetables protects against
      tumorigenesis. Thus, cruciferous vegetables have been of great interest for
      potential use in the chemoprevention of cancer. Cruciferous vegetables are rich
      source of glucosinolates, which are degraded into isothiocyanates by enzymatic
      action of plant-specific myrosinase or intestinal flora in the body. It appears
      that significant portion of the chemopreventive effects of isothiocyanates may be
      associated with the inhibition of the metabolic activation of carcinogens by
      cytochrome P450s (Phase I), coupled with strong induction of Phase II detoxifying
      and cellular defensive enzymes. Inductions of Phase II cellular enzymes are
      largely mediated by the antioxidant responsive element (ARE), which is regulated
      by the transcriptional factor, Nrf2. Additional potent regulatory mechanisms of
      Nrf2 include the different signaling kinase pathways (MAPK, PI3K, PKC and PERK)
      as well as other non-kinase dependent mechanisms. Moreover, apoptosis and cell
      cycle perturbations appear to be yet another potential chemopreventive mechanisms
      elicited by isothiocyanates, especially with respect to the effects on pre
      initiated or initiated tumor cells. Finally, modulation of other critical
      signaling mediators, including the NF-kappaB and AP-1 by a wide array of
      chemopreventive agents including isothiocyanates may also contribute to the
      overall chemopreventive mechanisms.

PMID- 15476861
TI  - The Lathyrus excitotoxin beta-N-oxalyl-L-alpha,beta-diaminopropionic acid is a
      substrate of the L-cystine/L-glutamate exchanger system xc-.
AB  - Beta-N-oxalyl-L-alpha-beta-diaminopropionic acid (beta-L-ODAP) is an unusual
      amino acid present in seeds of plants from the Lathyrus genus that is generally
      accepted as the causative agent underlying the motor neuron degeneration and
      spastic paraparesis in human neurolathyrism. Much of the neuropathology produced
      by beta-L-ODAP appears to be a direct consequence of its structural similarities
      to the excitatory neurotransmitter L-glutamate and its ability to induce
      excitotoxicity as an agonist of non-NMDA receptors. Its actions within the CNS
      are, however, not limited to non-NMDA receptors, raising the likely possibility
      that the anatomical and cellular specificity of the neuronal damage observed in
      neurolathyrism may result from the cumulative activity of beta-L-ODAP at multiple
      sites. Accumulating evidence suggests that system xc-, a transporter that
      mediates the exchange of L-cystine and L-glutamate, is one such site. In the
      present work, two distinct approaches were used to define the interactions of
      beta-L-ODAP with system xc-: Traditional radiolabel-uptake assays were employed
      to quantify inhibitory activity, while fluorometrically coupled assays that
      follow the exchange-induced efflux of L-glutamate were used to assess substrate
      activity. In addition to confirming that beta-L-ODAP is an effective competitive
      inhibitor of system xc-, we report that the compound exhibits a substrate
      activity comparable to that of the endogenous substrate L-cystine. The ability of
      system xc- to transport and accumulate beta-L-ODAP identifies additional
      variables that could influence its toxicity within the CNS, including the ability
      to limit its access to EAA receptors by clearing the excitotoxin from the
      extracellular synaptic environment, as well as serving as a point of entry
      through which beta-L-ODAP could have increased access to intracellular targets.

PMID- 15476862
TI  - Evaluation of gene expression profile of keratinocytes in response to JP-8 jet
      fuel.
AB  - The skin is the principal barrier against any environmental insult. Therefore,
      there is a high risk for a large number of military and civilian personnel
      exposed to jet fuel JP-8 to suffer percutaneous absorption of this fuel. This
      paper reports the use of cDNA microarray to identify the gene expression profile
      in normal human epidermal keratinocytes exposed to JP-8 for 24-h and 7-day
      periods. The effects of JP-8 exposure on keratinocytes at these two different
      periods induced a set of genes with altered expression in response to this type
      of insult. Microarray data were visualized using a novel algorithm based on
      simple statistical analyses to reduce data dimensionality and identify subsets of
      discriminant genes. Predictive neural networks were built using a multiplayer
      perceptron to carry out a proper classification task in microarray data in the
      untreated versus JP-8-treated samples. The pattern of expressions in response to
      JP-8 provides evidences that detoxificant-related and cell growth regulator genes
      with the most variability in the level of expression may be useful genetic
      markers in adverse health effects of personnel exposed to JP-8. The approaches in
      our analysis provide a simple, safe, novel, and effective method that is reliable
      in identifying and analyzing gene expression in samples treated with JP-8 or over
      potential toxic agents. Gene expression data from these studies can be used to
      build accurate predictive models that separate different molecular profiles. The
      data establish the use and effectiveness of these approaches for future
      prospective studies.

PMID- 15476863
TI  - Gene expression analysis of the rat testis after treatment with di(2-ethylhexyl)
      phthalate using cDNA microarray and real-time RT-PCR.
AB  - To investigate the effects of di(2-ethylhexyl) phthalate (DEHP) on gene
      expression in rat testis, 6-week-old male Sprague-Dawley rats were given a single
      oral dose of 20 or 2000 mg/kg and euthanized 3, 6, 24, or 72 h thereafter.
      Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)
      positive cells were significantly increased in the testis at 24 and 72 h after
      the exposure to 2000 mg/kg of DEHP. On cDNA microarray analysis, in addition to
      apoptosis-related genes, genes associated with atrophy, APEX nuclease, MutS
      homologue (E. coli), testosterone-repressed-prostatic-message-2 (TRPM-2),
      connective tissue growth factor, collagen alpha 2 type V, and cell adhesion
      kinase were differentially expressed. To investigate the relationship between
      histopathological alteration and gene expression, we selected genes associated
      with apoptosis and analyzed their expression by real-time quantitative reverse
      transcription-polymerase chain reaction (RT-PCR). With 20 mg/kg of DEHP
      treatment, bcl-2, key gene related to apoptosis, was increased. Up-regulation of
      bcl-2, inhibitor of Apaf-1/caspase-9/caspase-2 cascade of apoptosis, may be
      related to the fact that no morphological apoptotic change was induced after
      dosing of 20 mg/kg DEHP. With 2000 mg/kg of DEHP treatment, the apoptotic
      activator cascade, Fas/FasL, FADD/caspase-8/caspase-3 cascade, and Apaf-1/caspase
      9/caspase-2 cascade were increased and bcl-2 was decreased. Thus, these gene
      regulations might lead the cells into apoptosis in the case of high exposure to
      DEHP. In contrast, FADD/caspase-10/caspase-6 cascade and caspase-11/caspase-3
      cascade were not increased. These results indicate that the cascades of
      FADD/caspase-10/caspase-6 and caspase-11/caspase-3 are not related to apoptosis
      with DEHP treatment.

PMID- 15476864
TI  - The induction of cell cycle regulatory and DNA repair proteins in cisplatin
      induced acute renal failure.
AB  - The purpose of this study was to evaluate the expressions and the roles of
      proteins involved in cell cycle regulation and DNA repair in cis
      diamminedichloroplatinum (II) (cisplatin or CDDP)-induced acute renal failure
      (ARF). Treatment with CDDP (6 mg/kg, iv) induced tubular damage and increased
      serum creatinine (Scr) and the number of TUNEL-positive cells in the outer stripe
      of the outer medulla in rats, which reached peak levels at 5 days after CDDP. The
      expressions of cyclin-dependent kinase inhibitors (p21 and p27), cyclin B1,
      cyclin D1, PCNA, GADD 45, and GADD 153 were significantly increased in the outer
      medulla, reaching peak levels at 3 days after CDDP. Increments of p27 and PCNA
      were observed in the same nuclei. Sodium arsenite (SA), a heavy metal, attenuated
      tubular damage and increased Scr- and TUNEL-positive cells at 5 days after CDDP.
      SA augmented CDDP-induced increment of p27 but suppressed the increased
      expression of cyclin B1 and cyclin D1 at 3 days after CDDP. SA-induced
      attenuation of nephrotoxicity was associated with enhanced expression of
      proliferating cell nuclear antigen (PCNA) and growth-arrest and DNA damage (GADD)
      153 in damaged tubular cells. Our findings indicated that (1) proteins related to
      cell cycle regulation and DNA repair are induced in CDDP nephrotoxicity, (2) the
      SA-induced attenuation of CDDP nephrotoxicity is associated with increased
      expression of p27 and decreased expression of cyclin B1 and cyclin D1, they all
      induce cell cycle arrest at G1/S and G2/M, and (3) enhanced expression of DNA
      repair-related proteins is also associated with attenuation of CDDP
      nephrotoxicity.

PMID- 15476866
TI  - Neurotoxicity of carbonyl sulfide in F344 rats following inhalation exposure for
      up to 12 weeks.
AB  - Carbonyl sulfide (COS), a high-priority Clean Air Act chemical, was evaluated for
      neurotoxicity in short-term studies. F344 rats were exposed to 75-600 ppm COS 6 h
      per day, 5 days per week for up to 12 weeks. In rats exposed to 500 or 600 ppm
      for up to 4 days, malacia and microgliosis were detected in numerous
      neuroanatomical regions of the brain by conventional optical microscopy and
      magnetic resonance microscopy (MRM). After a 2-week exposure to 400 ppm, rats
      were evaluated using a functional observational battery. Slight gait abnormality
      was detected in 50% of the rats and hypotonia was present in all rats exposed to
      COS. Decreases in motor activity, and forelimb and hindlimb grip strength were
      also detected. In rats exposed to 400 ppm for 12 weeks, predominant lesions were
      in the parietal cortex area 1 (necrosis) and posterior colliculus (neuronal loss,
      microgliosis, hemorrhage), and occasional necrosis was present in the putamen,
      thalamus, and anterior olivary nucleus. Carbonyl sulfide specifically targeted
      the auditory system including the olivary nucleus, nucleus of the lateral
      lemniscus, and posterior colliculus. Consistent with these findings were
      alterations in the amplitude of the brainstem auditory evoked responses (BAER)
      for peaks N3, P4, N4, and N5 that represented changes in auditory transmission
      between the anterior olivary nucleus to the medial geniculate nucleus in animals
      after exposure for 2 weeks to 400 ppm COS. A concentration-related decrease in
      cytochrome oxidase activity was detected in the posterior colliculus and parietal
      cortex of exposed rats as early as 3 weeks. Cytochrome oxidase activity was
      significantly decreased at COS concentrations that did not cause detectable
      lesions, suggesting that disruption of the mitochondrial respiratory chain may
      precede these brain lesions. Our studies demonstrate that this environmental air
      contaminant has the potential to cause a wide spectrum of brain lesions that are
      dependent on the degree and duration of exposure.

PMID- 15476865
TI  - Role of tumor necrosis factor-alpha in the development of spontaneous hepatic
      toxicity in Long-Evans Cinnamon rats.
AB  - The objective of this study was to evaluate the potential role of TNF-alpha in
      the onset of acute hepatitis in the Long-Evans Cinnamon (LEC) rat, an animal
      model for inherited copper (Cu) toxicosis. In LEC rats, Cu is accumulated in the
      liver with age, and clinical signs of acute hepatitis were observed as, icterus,
      reduced body weight, nasal bleeding, dehydration, and reduced food intake at 12
      weeks of age. Cellular changes such as apoptosis in the liver were evident in
      these rats with increasing age. Positive TNF-alpha and TNFR1 immunostainings were
      observed in hepatocytes and Kupffer cells in LEC rats. Hepatic levels of caspase
      3 activity, TNF-alpha mRNA, and protein were also increased in LEC rats from 6 to
      12 weeks of age as compared with control Long-Evans (LE) rats. The neutralization
      of TNF-alpha by passive immunization or the inhibition of caspase activity can
      block the apoptotic process initiated by TNF-alpha. In this study, we evaluated
      the effects of passive immunization of LEC rats with weekly administration of
      anti-rat TNF-alpha on Cu-induced acute hepatitis. This treatment resulted in a
      reduction of the percentage of apoptotic cells in the liver, decreased activity
      of caspase-3, and also in down-regulation of the TNF-alpha gene expression. Thus,
      these results suggest a major role for TNF-alpha on the pathogenesis of Cu
      induced acute hepatitis in LEC rats.

PMID- 15476867
TI  - Chronic fuel oil toxicity in American mink (Mustela vison): systemic and
      hematological effects of ingestion of a low-concentration of bunker C fuel oil.
AB  - Petroleum oil enters the coastal marine environment through various sources;
      marine mammals such as sea otters that inhabit this environment may be exposed to
      low concentrations of petroleum hydrocarbons through ingestion of contaminated
      prey. The inability to perform controlled studies in free-ranging animals hinders
      investigations of the effects of chronic petroleum oil exposure on sea otter
      morbidity and mortality, necessitating the development of a reliable laboratory
      model. We examined the effects of oral exposure to 500 ppm bunker C fuel oil over
      113-118 days on American mink, a species phylogenetically related to the sea
      otter. Hematological parameters and organs were examined for fuel oil-associated
      changes. Hepatic cytochrome P4501A1 mRNA expression and fecal cortisol
      concentrations were also measured. Ingestion of fuel oil was associated with a
      decrease in erythrocyte count, hemoglobin concentration (Hgb), hematocrit (HCT),
      and an increase in mean corpuscular volume (MCV). Total leukocytes were elevated
      in the fuel oil group from increases in neutrophils, lymphocytes, and monocytes.
      Significant interactions between fuel oil and antigen challenge were found for
      erythrocyte parameters, monocyte and lymphocyte counts. Liver and adrenal weights
      were increased although mesenteric lymph node weights were decreased in the fuel
      oil group. Hepatic cytochrome P4501A1 mRNA was elevated in the fuel oil group.
      Fecal cortisol concentration did not vary between the two groups. Our findings
      show that fuel oil exposure alters circulating leukocyte numbers, erythrocyte
      homeostasis, hepatic metabolism and adrenal physiology and establish a framework
      to use mink as a model for sea otters in studying the systemic effects of marine
      contaminants.

PMID- 15476868
TI  - Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac
      mitochondrial toxicity.
AB  - The cardiotoxicity associated with doxorubicin (DOX) therapy limits the total
      cumulative dose and therapeutic success of active anticancer chemotherapy.
      Cardiac mitochondria are implicated as primary targets for DOX toxicity, which is
      believed to be mediated by the generation of highly reactive free radical species
      of oxygen from complex I of the mitochondrial electron transport chain. The
      objective of this study was to determine if the protection demonstrated by
      carvedilol (CV), a beta-adrenergic receptor antagonist with strong antioxidant
      properties, against DOX-induced mitochondrial-mediated cardiomyopathy [Toxicol.
      Appl. Pharmacol. 185 (2002) 218] is attributable to its antioxidant properties or
      its beta-adrenergic receptor antagonism. Our results confirm that DOX induces
      oxidative stress, mitochondrial dysfunction, and histopathological lesions in the
      cardiac tissue, all of which are inhibited by carvedilol. In contrast, atenolol
      (AT), a beta-adrenergic receptor antagonist lacking antioxidant properties,
      preserved phosphate energy charge but failed to protect against any of the
      indexes of DOX-induced oxidative mitochondrial toxicity. We therefore conclude
      that the cardioprotective effects of carvedilol against DOX-induced mitochondrial
      cardiotoxicity are due to its inherent antioxidant activity and not to its beta
      adrenergic receptor antagonism.

PMID- 15476869
TI  - The win locus involved in activation of the distal N-myc2 gene upon WHV
      integration in woodchuck liver tumors harbors S/MAR elements.
AB  - Woodchuck hepatitis virus (WHV) and the woodchuck (Marmota monax) are models for
      hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV). In woodchuck
      liver tumors, the N-myc2 proto-oncogene is frequently activated by WHV
      integration either close to the gene or in the b3n and win downstream loci,
      located 10 and 150 kb from N-myc2, respectively. A scaffold/matrix attachment
      region (S/MAR) regulative element was shown to be in b3n, possibly mediating
      activation of the upstream N-myc2 gene upon WHV integration. To investigate if
      S/MAR elements are in win too, a 17-kb DNA fragment corresponding to the major
      region of WHV insertion in this locus was cloned and sequenced. Overlapping
      subcloned fragments spanning candidate S/MARs predicted by sequence analysis were
      tested by standard in vitro binding assays. Results showed the presence of two
      S/MAR elements in win. The distribution of previously described WHV insertions
      relative to the S/MARs reinforces the hypothesis that S/MARs nearby distal WHV
      insertions might be involved in long-range activation of N-myc2.

PMID- 15476870
TI  - Interferon-beta and interferon-gamma synergistically inhibit the replication of
      severe acute respiratory syndrome-associated coronavirus (SARS-CoV).
AB  - Recent studies have shown that interferon-gamma (IFN-gamma) synergizes with IFN
      alpha/beta to inhibit the replication of both RNA and DNA viruses. We
      investigated the effects of IFNs on the replication of two strains of severe
      acute respiratory syndrome-associated coronavirus (SARS-CoV). While treatment of
      Vero E6 cells with 100 U/ml of either IFN-beta or IFN-gamma marginally reduced
      viral replication, treatment with both IFN-beta and IFN-gamma inhibited SARS-CoV
      plaque formation by 30-fold and replication by 3000-fold at 24 h and by > 1 x
      10(5)-fold at 48 and 72 h post-infection. These studies suggest that combination
      IFN treatment warrants further investigation as a treatment for SARS.

PMID- 15476871
TI  - Equine herpesvirus type 1 (EHV-1) glycoprotein K is required for efficient cell
      to-cell spread and virus egress.
AB  - The function of the equine herpesvirus type 1 (EHV-1) glycoprotein K (gK)
      homologue was investigated. Deletion of 88% of the UL53-homologous open reading
      frame in EHV-1 strain RacH resulted in a severe growth defect of the gK-negative
      virus (HDeltagK) as reflected by a significant decrease in the production of
      infectious virus progeny on RK13 cells. The HDeltagK virus induced only minute
      plaques, was unable to form syncytia, and its penetration efficiency into RK13
      cells was reduced by approximately 40%. To further analyze gK function and
      intracellular trafficking, gK of strain RacH was replaced by a C-terminally
      truncated gK-green fluorescent protein fusion protein (gK-GFP). The generated
      recombinant virus was shown to replicate well on non-complementing cells, and
      virus penetration and syncytium formation were comparable to parental RacH. A
      reduction in plaque size and slightly decreased intra- and extracellular virus
      titers, however, were observed. The gK-GFP fusion protein was expressed with
      early-late kinetics, and multiple forms of the protein exhibiting M(r)s between
      50,000 and 85,000 were detected by Western blot analysis. The various gK-GFP
      forms were shown to be N-glycosylated, associated with membranes of the Golgi
      apparatus, and were incorporated into extracellular virions. Complete processing
      of gK-GFP was only observed within the context of viral infection. From the
      results, we concluded that EHV-1 gK is required for efficient virus growth in
      vitro and that the carboxy-terminal amino acids are not required for its
      function, because the gK-GFP fusion protein was able to complement for EHV-1
      growth in the absence of authentic gK.

PMID- 15476872
TI  - Monoclonal antibodies differentially affect the interaction between the
      hemagglutinin of H9 influenza virus escape mutants and sialic receptors.
AB  - To determine the receptor binding properties of various H9 influenza virus escape
      mutants in the presence and absence of antibody, sialyloligosaccharides
      conjugated with biotinylated polyacrylamide were used. A mutant virus with a
      L226Q substitution showed an increased affinity for the Neu5Acalpha2-3Galbeta1
      4Glc. Several escape mutants viruses carrying the mutation N193D bound to
      Neu5Acalpha2-6Galbeta1-4GlcNAc considerably stronger than to Neu5Acalpha2
      6Galbeta1-4Glc. Several monoclonal antibodies unable to neutralize the escape
      mutants preserved the ability to bind to the hemagglutinin as revealed by enzyme
      linked immunosorbent assay. In each case, the bound monoclonal antibodies did not
      prevent the binding of the mutant HA to high affinity substrates and did not
      displace them from the virus binding sites. Together, these data suggest that
      amino acid changes selected by antibody pressure may be involved in the
      specificity of host-cell recognition by H9 hemagglutinin and in the ability of
      viruses with these mutations to escape the neutralizing effect of antibodies in a
      differential way, depending on the specificity of the host cell receptor. It may
      be important in the natural evolution of the H9 subtype, a plausible candidate
      for the agent likely to cause a future pandemic.

PMID- 15476873
TI  - Molecular and transcriptional analysis of the temperate lactococcal bacteriophage
      Tuc2009.
AB  - The genome of bacteriophage Tuc2009 consists of 38347 base pairs on which 57 open
      reading frames (ORFs) were identified, divided in two oppositely transcribed
      regions. The leftward-transcribed region harbors three ORFs, two of which are
      involved in the establishment of lysogeny. The rightward-transcribed region
      contains 54 ORFs, which are assumed to be required for the lytic life cycle. An
      exception to the above organization is ORF 10, of unknown function, located
      within the rightward-transcribed region that has an orientation opposite to the
      ORFs surrounding it. Transcriptional analysis of the Tuc2009 genome following
      infection of a sensitive host revealed that most ORFs are transcribed in a
      sequential manner. ORFs that are presumed to form (part of) the genetic switch
      along with the superinfection exclusion-encoding gene are transcribed immediately
      after infection, followed by transcription of the presumed replication region.
      Subsequent to this, several small transcripts could be identified followed by a
      single 24-kb transcript. This latter transcript was shown to specify most of the
      identified structural proteins as well as two proteins required for host lysis.
      Interestingly, the 24-kb mRNA was shown to undergo splicing through the activity
      of a type I intron whose removal from the mRNA resulted in the formation of an
      ORF specifying a major structural protein. Primer extension analysis was employed
      to identify the 5' ends of mRNA transcripts and the genome and transcriptional
      data are discussed in relation to other lactococcal bacteriophages.

PMID- 15476874
TI  - The NS3 protein of hepatitis C virus induces caspase-8-mediated apoptosis
      independent of its protease or helicase activities.
AB  - Apoptosis has been implicated in the pathogenesis of hepatitis C virus (HCV)
      related disease. Here, we show that expression of HCV NS3, or the NS2/NS3
      precursor protein, in mammalian cells results in induction of apoptosis and
      activation of caspases. HCV NS3-induced apoptosis was blocked by a caspase-8, but
      not a caspase-9-specific inhibitor. HCV NS3 coimmunoprecipitated with caspase-8,
      but not with other caspases or with FADD. Coexpression of HCV NS3 and caspase-8
      resulted in aggregation of the caspase in punctate structures that colocalized
      with HCV NS3. Cell lines stably expressing low levels HCV NS3 showed increased
      sensitivity to Fas-induced cell death. Point mutations of NS3 showed that the pro
      apoptotic function of the protein is distinct from its protease and helicase
      activities. These findings suggest that HCV NS3 promotes caspase-8 induced
      apoptosis at a pathway site distal to FADD, and that flavivirus NS3 may represent
      a new class of pro-apoptotic proteins.

PMID- 15476875
TI  - Cell lines that support replication of a novel herpes simplex virus 1 UL31
      deletion mutant can properly target UL34 protein to the nuclear rim in the
      absence of UL31.
AB  - Previous results indicated that the herpes simplex virus 1 (HSV-1) U(L)31 gene is
      necessary and sufficient for localization of the U(L)34 protein exclusively to
      the nuclear membrane of infected Hep2 cells. In the current studies, a bacterial
      artificial chromosome containing the entire HSV-1 strain F genome was used to
      construct a recombinant viral genome in which a gene encoding kanamycin
      resistance was inserted in place of 262 codons of the 306 codon U(L)31 open
      reading frame. The deletion virus produced virus titers approximately 10- to 50
      fold lower in rabbit skin cells, more than 2000-fold lower in Vero cells, and
      more than 1500-fold lower in CV1 cells, compared to a virus bearing a restored
      U(L)31 gene. The replication of the U(L)31 deletion virus was restored on U(L)31
      complementing cell lines derived either from rabbit skin cells or CV1 cells.
      Confocal microscopy indicated that the majority of U(L)34 protein localized
      aberrantly in the cytoplasm and nucleoplasm of Vero cells and CV1 cells, whereas
      U(L)34 protein localized at the nuclear membrane in rabbit skin cells, and U(L)31
      complementing CV1 cells infected with the U(L)31 deletion virus. We conclude that
      rabbit skin cells encode a function that allows proper localization of U(L)34
      protein to the nuclear membrane. We speculate that this function partially
      complements that of U(L)31 and may explain why U(L)31 is less critical for
      replication in rabbit skin cells as opposed to Vero and CV1 cells.

PMID- 15476876
TI  - Cell cycle regulation of human immunodeficiency virus type 1 integration in T
      cells: antagonistic effects of nuclear envelope breakdown and chromatin
      condensation.
AB  - We examined the influence of mitosis on the kinetics of human immunodeficiency
      virus type 1 integration in T cells. Single-round infection of cells arrested in
      G1b or allowed to synchronously proceed through division showed that mitosis
      delays virus integration until 18-24 h postinfection, whereas integration reaches
      maximum levels by 15 h in G1b-arrested cells. Subcellular fractionation of
      metaphase-arrested cells indicated that, while nuclear envelope disassembly
      facilitates docking of viral DNA to chromatin, chromosome condensation directly
      antagonizes and therefore delays integration. As a result of the balance between
      the two effects, virus integration efficiency is eventually up to threefold
      greater in dividing cells. At the single-cell level, using a green fluorescent
      protein-expressing reporter virus, we found that passage through mitosis leads to
      prominent asymmetric segregation of the viral genome in daughter cells without
      interfering with provirus expression.

PMID- 15476877
TI  - Enhancement of the immunogenicity of DNA vaccine against infectious bursal
      disease virus by co-delivery with plasmid encoding chicken interleukin 2.
AB  - The immunoregulatory activity of a nonmammalian interleukin 2 (IL-2), chicken IL
      2 (chIL-2), was investigated using a DNA vaccine against infectious bursal
      disease virus (IBDV) as a model. Coadministration of a plasmid encoding the VP2
      gene of IBDV (pCI-VP2) and a plasmid encoding chicken IL-2 gene (pCI-chIL-2)
      enhances bursal protection against both the homologous IBDV strain ZJ2000 and the
      heterologous strain BC6/85 compared to administration of pCI-VP2 alone.
      Vaccination with pCI-VP2 alone induces low bursal protection against ZJ2000 and
      only protects chickens from clinical outbreaks and mortality, but not from bursal
      damage caused by BC6/85. Co-administration of the plasmid encoding the
      polyprotein gene of IBDV (pCI-VP2/4/3) and pCI-chIL-2 provides complete
      protection (15/15) against ZJ2000 and satisfactory protection (13/15) against
      BC6/85. In contrast, only 10 out of 15 chickens and 6 out of 15 chickens were
      protected against ZJ2000 and BC6/85, respectively, using the pCI-VP2/4/3
      vaccination alone. A significant increase in the IBDV-specific neutralizing
      antibody response was also observed in chickens that received pCI-VP2/4/3 plus
      pCI-chIL-2 as compared with those that received the pCI-VP2/4/3 vaccination
      alone. By administrating different amounts of plasmid DNA, we confirmed that the
      pCI-chIL-2, but not the backbone plasmid pCI, contributes to increased
      immunoprotection of DNA vaccine against IBDV. These results strongly indicate
      that the efficacy of avian DNA vaccine can be modulated by co-administration of a
      plasmid encoding chIL-2.

PMID- 15476878
TI  - Molecular clock-like evolution of human immunodeficiency virus type 1.
AB  - The molecular clock hypothesis states that the rate of nucleotide substitution
      per generation is constant across lineages. If generation times were equal across
      lineages, samples obtained at the same calendar time would have experienced the
      same number of generations since their common ancestor. However, if sequences are
      not derived from contemporaneous samples, differences in the number of
      generations may be misinterpreted as variation in substitution rates and hence
      may lead to false rejection of the molecular clock hypothesis. A recent study has
      called into doubt the validity of clock-like evolution for HIV-1, using molecular
      sequences derived from noncontemporaneous samples. However, after separating
      their within-individual data according to sampling time, we found that what
      appeared to be nonclock-like behavior could be attributed, in most cases, to
      noncontemporaneous sampling, with contributions also likely to derive from
      recombination. Natural selection alone did not appear to obscure the clock-like
      evolution of HIV-1.

PMID- 15476879
TI  - Multiple residues in the extracellular domains of CCR3 are critical for
      coreceptor activity.
AB  - Human immunodeficiency virus type 1 (HIV-1) binds to the human CD4 (hCD4) and a
      coreceptor to enter permissive human cells. The chemokine receptors, hCCR5 and
      hCXCR4, are the primary coreceptors used by HIV-1 isolates in vivo, however,
      hCCR3 has been implicated as a coreceptor for HIV infection of the central
      nervous system. To determine the domains and amino acids important in hCCR3
      coreceptor activity, chimeras between the permissive hCCR3 and the non-permissive
      rhesus macaque CCR3 (RhCCR3) were constructed and assessed for coreceptor
      activity for two R5 strains of HIV-1 (YU-2 and ADA) and one R5X4 strain (89.6).
      Even though three extracellular domains of CCR3 participated in coreceptor
      activity for the two R5 isolates (ECD-1, ECD-3, and ECD-4), for the R5X4 isolate,
      ECD-4, and to a lesser extent ECD-3, were critical for coreceptor activity. In
      addition, residues 13 and 20 in ECD-1, residue 179 in ECD-3, and residue in 271
      in ECD-4 of CCR3 were identified for HIV-1 envelope-mediated entry for R5
      isolates. In contrast, all the residues on ECD-4 appeared necessary for
      coreceptor activity for HIV-1(89.6). Therefore, multiple residues on multiple
      extracellular domains of hCCR3 are important for coreceptor activity for HIV-1.

PMID- 15476880
TI  - Enhancement of dengue virus translation: role of the 3' untranslated region and
      the terminal 3' stem-loop domain.
AB  - An essential step for a productive infection by the dengue flavivirus (DEN) is
      translation of the m(7)G-capped, nonpolyadenylated positive-sense RNA genome. We
      have recently identified sequences within the DEN 3' untranslated region (UTR)
      that modulate viral translation. Here, we show that the DEN type 2 (DEN2) 3'UTR
      stimulated translation of m(7)G-capped DEN2 5'UTR-containing reporter mRNAs in
      baby hamster kidney (BHK) cells compared to a 3' vector sequence. Analogous to
      the 3' poly(A) tail, the DEN2 3'UTR also enhanced translation of reporter mRNAs
      containing (i) a nonfunctional A cap, (ii) the 5'UTR of human beta-globin, or
      (iii) a viral internal ribosome entry site (IRES). In all cases, approximately
      half of the translation efficiency was due to the terminal 3' stem-loop (3'SL)
      domain. In addition, the 3'SL domain increased the association of mRNAs with
      polysomes. Together, these results indicate that the DEN2 3'UTR, mediated in part
      by the 3'SL domain, enhances translation initiation, possibly after recognition
      of the 5' cap structure.

PMID- 15476881
TI  - Phage-induced change in the stability of mRNAs.
AB  - The stability of mRNA in Escherichia coli cells changed after phage T4 infection.
      Stable E. coli mRNAs such as lpp and ompA were drastically destabilized
      immediately after infection. In contrast, T4 phage soc mRNA that had been
      unstable before infection became stabilized after infection. The host RNases E
      and G both contributed to the destabilization of these mRNAs. Accordingly, these
      RNases may alter their target RNAs before and after infection. An RNA chaperon,
      Hfq, and polyadenylation at 3' ends of mRNA are known key factors for
      destabilization of ompA and lpp mRNAs in uninfected cells. However, they had no
      effect on the destabilization of E. coli mRNAs after infection. On the other
      hand, T4 infection in the presence of rifampicin or infection of a deletion
      mutant, Deltatk2, did not destabilize the host mRNAs. These results strongly
      suggest that a phage-encoded factor is responsible for the destabilization of
      host mRNAs. Destabilization of host mRNAs was also observed after infection by
      phages T2 and T7.

PMID- 15476882
TI  - Inhibition of the stress-activated kinase, p38, does not affect the virus
      transcriptional program of herpes simplex virus type 1.
AB  - To investigate the impact of stress kinase p38 activation on HSV-1 transcription,
      we performed a global transcript profile analysis of viral mRNA using an
      oligonucleotide-based DNA microarray. RNA was isolated from Vero cells infected
      with the KOS strain of HSV-1 in the presence or absence of SB203580, a pyridinyl
      imidazole inhibitor of p38. Under conditions that eliminated ATF2 activation but
      had no effect on c-Jun, and reduced virus yield by 85-90%, no effect on
      accumulation of viral IE, DE, or L transcripts was observed by array analysis or
      selected Northern blot analysis at 2, 4, and 6 h post infection. Results of array
      data from cells infected with the ICP27 mutant d27-1 in the presence or absence
      of SB203580 only reflected the known restricted transcription phenotype of the
      ICP27 mutant. This result is consistent with a role for p38 activation on virus
      replication lying downstream of the essential role of ICP27 in DE and perhaps
      late transcription regulation. No effect of SB203580 on transcription was
      detected after infection with the ICP0 mutant 7134, at 0.5 or 5.0 PFU/cell,
      though decreases in the rate of accumulation of all kinetic classes of mRNA could
      be detected, relative to wt virus. These results indicate that inhibiting p38
      activity in Vero cells, while significantly reducing wt virus yield, demonstrated
      no obvious impact on the program of viral transcription.

PMID- 15476883
TI  - Functional relationship between the matrix proteins of feline and simian
      immunodeficiency viruses.
AB  - To investigate the functional relationship between the matrix (MA) proteins of
      feline and simian immunodeficiency viruses (FIV and SIV, respectively), we
      generated chimeric proviruses in which the MA-coding region of an SIV infectious
      molecular clone was partially or fully replaced by its FIV counterpart. Chimeric
      SIV proviruses containing the amino-terminal 36 residues or the central and
      carboxy-terminal regions of the FIV MA assembled into virions as efficiently as
      wild-type SIV. However, the resulting virions were noninfectious in single-cycle
      infectivity assays. Furthermore, a chimeric SIV provirus containing the entire
      FIV MA was found to be severely impaired in virion production due to inefficient
      membrane binding of the chimeric Gag polyprotein. Interestingly, the assembly
      defective phenotype of this chimeric Gag precursor could be reversed either by
      introducing the G31K/G33K double amino acid substitution in the FIV-derived MA
      domain or by coexpression with wild-type SIV Gag. Of note, a chimeric FIV
      provirus expressing the SIV MA not only assembled into particles as efficiently
      as wild-type FIV, but also replicated in feline T cells with wild-type kinetics.
      Our results thus provide novel information about the functional homology between
      the MA proteins of distantly related lentiviruses.

PMID- 15476884
TI  - The molecular epidemiology of dengue virus serotype 4 in Bangkok, Thailand.
AB  - Dengue represents a major public health problem in Thailand, with all four viral
      serotypes co-circulating. Dengue virus serotype 4 (DENV-4) is the least
      frequently sampled serotype, although one that is often associated with
      hemorrhagic fever during secondary infection. To determine the evolutionary
      forces shaping the genetic diversity of DENV-4, and particularly whether its
      changing prevalence could be attributed to instances of adaptive evolution in the
      viral genome, we undertook a large-scale molecular epidemiological analysis of
      DENV-4 in Bangkok, Thailand, using both E gene and complete coding region
      sequences. This analysis revealed extensive genetic diversity within a single
      locality at a single time, including the discovery of a new and divergent
      genotype of DENV-4, as well as a pattern of continual lineage turnover. We also
      recorded the highest average rate of evolutionary change for this serotype, at
      1.072 x 10(-3) nucleotide substitutions per site, per year. However, despite this
      abundant genetic variation, there was no evidence for adaptive evolution in any
      gene, codon, or lineage of DENV-4, with the highest rate of nonsynonymous
      substitution observed in NS2A. Consequently, the rapid turnover of DENV-4
      lineages through time is most likely the consequence of a high rate of
      deleterious mutation in the viral genome coupled to seasonal fluctuations in the
      size of the vector population.

PMID- 15476885
TI  - Characterization of human immunodeficiency virus type 1 Pr160 gag-pol mutants
      with truncations downstream of the protease domain.
AB  - We have constructed a series of HIV-1 Gag-pol mutants by progressive deletion of
      the pol sequence downstream of the viral protease (PR) domain. Effects of the
      truncation mutations on virus particle production and Gag particle processing
      were analyzed. Analysis indicated that removal of the integrase (IN) domain had
      no major effect on the efficiency of particle processing, but resulted in a
      marked reduction in virus particle budding. Deletion of both the IN and RNase H
      domains, however, restored the production of virus particles to wild-type level.
      The proteolytic processing of virus particle was significantly impaired when the
      p51RT domain was truncated. All of the truncated Gag-pol proteins could be
      incorporated into virus particles and demonstrated an immunofluorescence staining
      pattern similar to that of the wild type (wt). Our data are consistent with the
      proposal that signals for directing the Gag-pol transport and particle
      incorporation are determined by its N-terminal Gag domain. Truncated Gag-pol
      retaining an intact p51RT was able to complement a PR-defective mutant to produce
      infectious pseudotyped virions, with a virus titer 20-70% of that of wt.
      Pseudotyped virions produced by the Gag-pol lacking an intact p51RT were
      noninfectious or poorly infectious. This suggests that an intact p51RT domain is
      required for the Gag-pol to mediate production of mature infectious virus
      particles in trans.

PMID- 15476886
TI  - Human papillomavirus type 16 E7 protein increases acetylation of histone H3 in
      human foreskin keratinocytes.
AB  - Histone acetylation plays an important role in chromatin remodeling and
      transcription control. Acetylation of histones is regulated by histone
      acetyltransferases and histone deacetylases (HDACs). Human papillomavirus type 16
      (HPV16) E7 can inactivate retinoblastoma protein (pRB), which recruits histone
      deacetylases, and also physically interacts with histone acetyltransferases and
      histone deacetylases, suggesting E7 may affect histone acetylation. To test this,
      we have analyzed the state of acetylation of histone H3 in human foreskin
      keratinocytes. HPV16 E7 increased acetylation of histone H3 on lysine 9, which is
      related to transcription activation. The ability to bind both pRB and histone
      deacetylase was required for HPV16 E7 to increase histone acetylation. Chromatin
      immunoprecipitations showed HPV16 E7 increases histone acetylation on the E2F1
      and cdc25A promoters. Consistent with this, RT-PCR analysis showed an increase in
      the expression of E2F-responsive genes involved in cell cycle control. HPV16 E7
      affected neither the steady-state levels of histone acetyltransferases or
      deacetylases nor histone deacetylase activity. However, HPV16 E7 did increase the
      level of methylation of histone H3 on lysine 4, which normally requires
      displacement of histone deacetylase. In contrast, sodium butyrate, a known
      inhibitor of histone deacetylases, caused an increase in acetylated but not
      methylated histone H3. These data suggest HPV16 E7, by increasing histone
      acetylation, may create a transcriptionally active chromatin structure to promote
      expression of genes vital for cell cycle progression.

PMID- 15476890
TI  - Illegitimate recombination mediated by double-strand break and end-joining in
      Escherichia coli.
AB  - The frequency of illegitimate recombination has been measured by a lambdabio
      transducing phage assay during the induction of the E. coli lambda c1857 lysogen.
      Illegitimate recombination falls into two classes, short homology-independent and
      short homology-dependent illegitimate recombination. The former involves
      sequences with virtually no homology, and is mediated by DNA topoisomerases and
      controlled by the DNA binding protein HU. The latter is induced by UV irradiation
      or other DNA damaging agents and requires short regions of homology, usually
      contain 4 to 13 base pairs, at sites involved in recombination. It has been shown
      that the RecJ exonuclease promotes short homology-dependent illegitimate
      recombination, but that the RecQ helicase suppresses it. In addition, we have
      shown that the overexpression of RecE and RecT enhances the frequencies of
      spontaneous and UV-induced illegitimate recombination and that the RecJ, RecF,
      RecO, and RecR functions are required for this RecE-mediated illegitimate
      recombination. Moreover, we have also indicated that RecQ plays a role in the
      suppression of RecEmediated illegitimate recombination, with the participation of
      DnaB, Fis, Exol, and H-NS. Models have been proposed for these modes of
      recombination: the DNA gyrase subunit exchange model for short homology
      independent illegitimate recombination and the "double-strand break and join"
      model for short homologydependent illegitimate recombination. Many features of
      these models remain to be tested in future studies.

PMID- 15476887
TI  - The cowpox virus host range gene, CP77, affects phosphorylation of eIF2 alpha and
      vaccinia viral translation in apoptotic HeLa cells.
AB  - Host restriction of vaccinia virus has been previously described in CHO and RK13
      cells in which a cowpox virus CP77 gene rescues vaccinia virus growth at the
      viral protein translation level. Here we investigate the restrictive stage of
      vaccinia virus in HeLa cells using a vaccinia mutant virus (VV-hr) that contains
      a deletion of 18-kb genome sequences resulting in no growth in HeLa cells.
      Insertion of CP77 gene into VV-hr generated a recombinant virus (VV-36hr) that
      multiplied well in HeLa cells. Both viruses could enter cells, initiate viral DNA
      replication and intermediate gene transcription. However, translation of viral
      intermediate gene was only detected in cells infected with VV-36hr, indicating
      that CP77 relieves host restriction at the intermediate gene translation stage in
      HeLa cells. Caspase-2 and -3 activation was observed in HeLa cells infected with
      VV-hr coupled with dramatic morphological alterations and cleavage of the
      translation initiation factor eIF4G. Caspase activation was reduced in HeLa cells
      infected with VV-36hr, indicating that CP77 acts upstream of caspase activation.
      Enhanced phosphorylation of PKR and eIF2alpha was also observed in cells infected
      with VV-hr and was suppressed by CP77. Suppression of eIF4G cleavage with the
      caspase inhibitor ZVAD did not rescue virus translation, whereas expression of a
      mutant eIF2alpha protein with an alanine substitution of serine at amino acid
      position 51 (eIF2alphaS51A) partially restored viral translation and moderately
      increased virus growth in HeLa cells.

PMID- 15476891
TI  - Genetic and physiological regulation of non-homologous end-joining in mammalian
      cells.
AB  - Repair of DSBs is important to prevent chromosomal fragmentation, translocations
      and deletions. To investigate the process in NHEJ, we have established an in
      vitro system to clarify the measurement and analysis of the efficiency and the
      fidelity of rejoining of DSBs, and applied the method to investigate NHEJ in
      human cells derived from patients suffering from cancer-prone hereditary
      diseases. A DSB was introduced in plasmid pZErO-2 at a specific site within the
      ccdB gene that is lethal to E. coli cells, and treated with nuclear extracts from
      human cells. The efficiency of rejoining in the nuclear extract from an A-T cell
      line was comparable to that from a control cell line. However, the accuracy of
      rejoining was much lower for the A-T cell extract than for the control cell
      extract. All mutations were deletions, most of which contained short direct
      repeats at the breakpoint junctions. The deletion spectrum caused by the A-T
      nuclear extract was distinct from that by the control extract. These results
      indicate that A-T cells have certain deficiencies in end-joining of double-strand
      breaks in DNA. The extract from BS cells also showed the similar activity and the
      lower fidelity of rejoing compared to that from normal cells. From the sequencing
      analysis of the junction of DSBs, it is speculated that the defect in the BLM
      helicase might cause irregular rejoining of DSBs. Radioadaptive response is the
      acquirement of cellular resistance to ionizing radiation by prior exposure to low
      dose. We investigated the in vitro end-joining activity of DNA ends in
      radioadaptive cells. Both the efficiency and the fidelity of rejoining in the
      cells pre-exposed to low dose are increased comparing to those without pre
      exposure. We also investigated the joining activity of DNA ends in p53-deficient
      cells. Pre-irradiation caused no apparent alteration in both the efficiency and
      fidelity of end-joining. These results suggest that the exposure to low dose
      activates a cellular function to repair DSBs efficiently, which is dependent on
      p53. These results indicate that NHEJ pathway is regulated by many factors;
      genetic regulation by ATM and BLM, and physiological conditions such as
      irradiation with ionizing radiation. The observations also suggest that in some
      occasions p53 might play a key role in NHEJ.

PMID- 15476892
TI  - The function of RecQ helicase gene family (especially BLM) in DNA recombination
      and joining.
AB  - Bloom syndrome is a rare autosomal recessive genetic disorder characterized by
      lupus-like erythematous telangiectasias of the face, sun sensitivity, stunted
      growth, and immunodeficiency. Chromosome instability syndromes have a common
      feature, being associated at high frequency with neoplasia. BS is considered as
      one of the chromosome instability syndromes since the fibroblasts or lymphocytes
      of BS patients show excessive spontaneous chromosome instability. The causative
      gene of BS (BLM) was identified as a RecQ helicase homologue. In this review, we
      showed the characteristic phenotypes of BS, especially two Japanese siblings. In
      the latter of the review, the functional domains of BLM, those are nuclear
      localization signal and the interacting proteins such as ATM, are shown. Several
      lines of reports indicates that BLM helicase is involved in the re-initiation of
      DNA replication at sites where replication forks have arrested or collapsed. To
      elucidate the precise function of RecQ helicase in DNA repair and replication
      aims not only to improve our understanding of the molecular basis for
      tumorigenesis, but also to extend the range of potential therapeutic targets.

PMID- 15476893
TI  - Nijmegen breakage syndrome and DNA double strand break repair by NBS1 complex.
AB  - The isolation of the NBS1 gene revealed the molecular mechanisms of DSB repair.
      In response to DNA damage, histone H2AX in the vicinity of DSBs is phosphorylated
      by ATM. NBS1 then targets the MRE11/RAD50 complex to the sites of DSBs through
      interaction of the FHA/BRCT domain with gamma-H2AX. NBSI complex binds to damaged
      DNA directly, and HR repair is initiated. To collaborate DSB repair, ATM also
      regulates cell cycle checkpoints at GI, G2, and intra-S phases via
      phosphorylation of SMC, CHK2 and FANCD2. The phosphorylation of these proteins
      require NBS1 complex. Thus, NBSI has at least two important roles in genome
      maintenance, as a DNA repair protein in HR pathway and as a signal modifier in
      intra-S phase checkpoints. NBSI is also known to be involved in maintenance of
      telomores, which have DSB-like structures and defects here can cause telomcric
      fusion. Therefore, NBS1 should be a multi-functional protein for the maintenance
      of genomic integrity. Further studies on NBS1 will provide insights into the
      mechanisms of DNA damage response and the network of these factors involved in
      genomic stability.

PMID- 15476894
TI  - Cell death promoted by homologous DNA interaction from bacteria to humans.
AB  - Pairing between homologous DNA controls cellular functions including double
      strand break repair, mitotic recombination, and progression of DNA replication
      forks, as well as chiasma formation during meiosis. Here I summarize that
      homologous interaction could promote the cell killing in bacteria, yeast, and
      multicellular organisms. The mechanisms of cell killing are categorized into two
      types: (1) the killing due to the accumulation of extrachromosomal DNA; (2) the
      killing induced by Holliday junction structures. I propose that the mechanisms of
      such killing function as novel apoptotic pathways in the cells carrying severe
      DNA damages to eliminate such damages from cell population.

PMID- 15476896
TI  - Intermediate molecules generated by transposase in the pathways of transposition
      of bacterial insertion element 1S3.

PMID- 15476895
TI  - Gpt delta transgenic mouse: A novel approach for molecular dissection of deletion
      mutations in vivo.
AB  - Human genome is continuously exposed to various DNA damaging agents including
      reactive oxygen species. Of various forms of DNA damage, double-strand breaks
      (DSBs) in DNA are the most detrimental because of the mutagenicity and
      cytotoxicity. To combat the serious threats posed by DSBs, cells evolved various
      homologous and non-homologous recombination repair mechanisms. However, some
      repair mechanisms appear to be involved in the induction of genome rearrangements
      such as deletions. To analyze the deletion mutations in a whole body system, gpt
      delta mice were established. In this mouse model, deletions in lambda, DNA
      integrated in the chromosome are preferentially selected as Spi(-) phages, which
      can then be subjected for molecular analysis. Here, we reported the sequence
      characteristics of deletions induced by ionizing radiations in the liver,
      ultraviolet light beta in the epidermis, mitomycin C in the bone marrow and
      heterocyclic amine PhIP in the colon. To our knowledge, this is the first report
      in which in vivo deletion mutations are systematically analyzed at the molecular
      level. About half of the large deletions occur between short direct-repeat
      sequences and the remainder had flush ends, suggesting that they are generated
      during the repair of DSBs in DNA. The results also suggest that mutation
      induction and repair mechanisms may vary depending on the type of organs/tissues
      examined, i.e., germ cells versus somatic cells or highly proliferating cells
      versus slowly proliferating cells. Possible mechanisms of intrachromosomal
      deletion mutations are discussed.

PMID- 15476897
TI  - Genetics and epigenetics in flower pigmentation associated with transposable
      elements in morning glories.
AB  - Among the genus Ipomoea, three morning glories, I. nil the Japanese morning
      glory), I. purpurea (the common morning glory), and I. tricolor, were
      domesticated well for floricultural plants, and many spontaneous mutants
      displaying various flower pigmentation patterns were isolated. Most of these
      spontaneous mutations were found to be caused by the insertion of DNA
      transposable elements in the genes for the anthocyanin pigmentation in flowers,
      and many of them exhibited variegated flowers, such as white flowers with
      pigmented spots and sectors. Here, we describe the historical background of the
      mutants displaying variegated flowers and review the genetic and epigenetic
      regulation in flower pigmentation associated with transposable elements of these
      morning glories. The flecked, speckled, r-1, and purple mutations in I. nil were
      caused by insertions of Tpnl and its relatives in the En/Spm superfamily, Tpn2,
      Tpn3, and Tpn4, into the genes for anthocyanin coloration in flowers,i.e., DFR-B,
      CHI, CHS-D, and InNHXI, respectively. Similarly, the flaked and pink mutants of
      I. purpurea have distantly related elements, Tip100 and Tip201, in the Ac/Ds
      superfamily inserted into the CHS-D and F3'H genes, respectively. The flower
      variegation patterns can be determined by the frequency and timing of the
      excision of these transposons, and their stable insertions produce plain color
      flowers without generating pigmented spots or sectors; furthermore, both genetic
      and epigenetic regulation appeared to play important roles in determining the
      frequency and timing of the excision of the transposons. However, flower
      variegation is not always associated with the excision of an integrated DNA
      transposon from one of the genes for anthocyanin pigmentation. The mutant Flying
      Saucers of I. tricolor displaying variegated flowers was found to have the
      transposon ItMULE inserted into the DFR-B promoter region, but no excision of
      ITMULEL from the DFR-B could be detected in the variegated flower lines. The
      instable pearly-vrg allele in cv. Flying Saucers is likely to be an epiallele
      because the DNA methylation in the DFR-B promoter appeared to be associated with
      flower pigmentation.

PMID- 15476898
TI  - Transposition mechanisms and biothechnology applications of the medaka fish tol2
      transposable element.
AB  - The Tol2 element of the medaka fish is a member of the hAT (hobo/Activator/Tam3)
      transposable element family. About 20 copies are present in the medaka fish
      genome and, unlike many other hAT family elements, virtually all the copies are
      autonomous or potentially autonomous, containing an intact transposase gene.
      Excision of Tol2 is not precise at the nucleotide sequence level, excision
      footprints being heterogeneous. In more than half of excision events, however,
      breakage and rejoining of DNA molecules occur within the 8-bp target site
      duplication region, removing the entire Tol2 sequence and retaining parts of the
      target site duplications. In the reminder of the excision events, either the left
      or the right terminal region is left and the other end is lost together with its
      flanking region. Thus, there might be two different mechanisms of excision.
      Insertion of Tol2 occurs without detectable preference for target sequences and
      creates a target site duplication of exactly 8 bp. In addition to the medaka fish
      and related fish species, Tol2 transposes in mammalian cells in culture,
      including human and mouse examples. Autonomy is also retained in these cases. A
      gene transfer vector using Tol2 has already been established in fish. Foreign DNA
      fragements inserted in Tol2 can be efficiently delivered to the chromosomes by
      transposition. The latest version of the vector contains, between the Tol2
      terminal regions, a bacterial drug-resistance gene and a plasmid replication
      origin. This allows simple recovery of insertion regions, as plasmid DNA, from
      genomic DNA of transformants. Modification of this system for other vertebrates,
      especially for mammals, are now in progress.

PMID- 15476899
TI  - Structure and function of the shufflon in plasmid r64.
AB  - Conservative site-specific recombination plays key roles in creating biological
      diversity in prokaryotes. Most site-specific inversion systems consist of two
      recombination sites and a recombinase gene. In contrast, the shufflon multiple
      inversion system of plasmid R64 consists of seven sfx recombination sites, which
      separate four invertible DNA segments, and the rci gene encoding a site-specific
      recombinase of the integrase family. The rci product mediates recombination
      between any two inverted sfx sites, resulting in the inversion of four DNA
      segments independently or in groups. Random shufflon inversions construct seven
      pilV genes encoding constant N-terminal segment with different C-terminal
      segments. The pilV products are tip-located adhesins of the type IV pilus, called
      the thin pilus, of R64 and recognize lipopolysaccharides of recipient bacterial
      cells during R64 liquid matings. Thus, the shufflon determines the recipient
      specificity of liquid matings. Rci protein of R64 was overexpressed, purified,
      and used for in vitro recombination reactions. The cleavage and rejoining of DNA
      strands in shufflon recombinations were found to take place in the form of a 5'
      protruding 7-hp staggered cut within sfx sequences. Thus, the sfx sequence is
      asymmetric: only the 7-bp spacer sequence and the right arm sequence are
      conserved among various R64 sfxs, whereas the sfx left arm sequences are not
      conserved. Rci protein was shown to bind to entire sfx sequences, suggesting that
      it binds to the right arms of the sfx sequences in a sequence-specific manner and
      to their left arms in a non-sequence-specific manner. The sfx left arm sequences
      greatly affected the shufflon inversion frequency. The artificial symmetric sfx
      sequence, in which the sfx left arm was changed to the inverted repeat sequence
      of the right arm, exhibited the highest inversion frequency. Rci-dependent
      deletion of a DNA segment flanked by two symmetric sfx sequences in direct
      orientation was observed, suggesting that the asymmetry of sfx sequences may
      prevent recombination between sfx sequences in direct orientation in the R64
      shufflon. The Rci C-terminal domain was not required for recombination using the
      symmetric sfx sequence. A model, where the C-terminal domain of Rci protein plays
      a key role in the sequence-specific and non-specific binding of Rci to asymmetric
      sfx sites, was proposed. Site-specific recombination in the temperate phage Mx8
      of M. xanthus was also described. The Mx8 attP site is located within the coding
      sequence of the Mx8 intP gene. Therefore, the integration of Mx8 into the M.
      xanthus chromosome results in the conversion of the intP gene into a new gene,
      intP. As a result of this conversion, the 112-amino-acid C-terminal sequence of
      the intP product is replaced with a 13-amino acid sequence of the intR product.
      The C-terminal domain of Mx8 IntP recombinase is only required for integration
      and not for excision.

PMID- 15476900
TI  - Molecular mechanism of vde-initiated intein homing in yeast nuclear genome.
AB  - In Saccharomyces cerevisiae, VMAI intein encodes a homing endonuclease termed VDE
      which is produced by an autocatalytic protein splicing reaction. VDE introduces a
      DSB at its recognition sequence on intein-minus allele, resulting in the lateral
      transfer of VMAI intein. In this review, we summarize a decade of in vitro study
      on VDE and describe our recent study on the in vivo behavior of both VDE and host
      proteins involved in intein mobility. Meiotic DSBs caused by VDE are repaired in
      the similar pathway to that working in meiotic recombination induced by Spollp
      mediated DSBs. Meiosis-specific DNA cleavage and homing is shown to be guaranteed
      by the two distinct mechanisms, the subcellular localization of VDE and a
      requirement of premeiotic DNA replication. Based on these lines of evidence, we
      present the whole picture of molecular mechanism of VDEinitiated homing in yeast
      cells.

PMID- 15476901
TI  - Optimizing antimicrobial pharmacodynamics: dosage strategies for meropenem.
AB  - INTRODUCTION: Carbapenems are broad-spectrum antibiotics that are often employed
      as the last line of therapy for patients with nonresponsive nosocomial
      infections. Consideration of pharmacodynamic principles in dosage regimens for
      these agents can maximize their antibacterial effectiveness and reduce the number
      of bacterial strains that survive to mutate or continue infection. OBJECTIVE: The
      objectives of this review were to highlight examples of the application of
      pharmacodynamics to the carbapenems (particularly meropenem) and to comment on
      clinical utility of these dosage regimens. METHODS: Relevant information was
      identified through a MEDLINE search of the literature (1980-present) using the
      terms carbapenem, pharmacodynamic, pharmacokinetic, pharmacoeconomic, meropenem,
      imipenem, ertapenem, biapenem, and panipenem. Additionally, meeting posters were
      identified from the International Conference of Antimicrobial Agents and
      Chemotherapy (years 2001-2003) and the International Conference of the American
      Thoracic Society (years 2002-2003). All studies demonstrating the
      pharmacodynamics of the carbapenems by incorporating changes in dosage strategies
      were included. RESULTS: Only relevant data for meropenem were identified in our
      literature search. The dosage scheme for meropenem may be modified to maximize
      the percentage of the dosage interval that drug concentrations remain above the
      minimum inhibitory concentration, an important parameter related to the bacterial
      kill rate. Only relevant data for meropenem were identified in our literature
      search. Human volunteer and Monte Carlo simulation studies suggested that in the
      treatment of susceptible pathogens, higher meropenem doses, increased frequency
      of administration, or prolonged duration of infusion resulted in improved
      pharmacodynamics. CONCLUSION: When proper pharmacodynamic principles are applied
      to dosage strategies for meropenem, clinical and microbiological outcomes can be
      optimized.

PMID- 15476902
TI  - Role of aromatase inhibitors in the treatment of breast cancer.
AB  - BACKGROUND: Estrogens play a pivotal role in the development of breast cancer.
      Endocrine therapy based on estrogen blockade is a well-established treatment in
      hormone-dependent breast cancer. Tamoxifen citrate has long been considered the
      "gold standard" due to its relative safety and efficacy. Aromatase inhibitors are
      anti-estrogen agents that target specifically the aromatase enzyme, which is the
      final step in the estrogen production. The first use of aromatase inhibitors in
      breast cancer was associated with adverse effects such as rash, drowsiness, and
      adrenal-gland suppression. Newer third-generation agents are emerging as
      potential alternatives to tamoxifen, associating clinical efficacy with a more
      favorable safety profile. OBJECTIVES: The aim of this article is to review the
      mechanisms of actions pharmacology, adverse effects, and clinical applications of
      the aromatase inhibitors available in the United States. METHODS: The terms
      breast cancer or neoplasia, aromatase, aromatase inhibitors, third-generation,
      endocrine therapy, and antiestrogens were used to search MEDLINE for English
      language studies published between 1966 and April 2004. A parallel search was
      performed at the corresponding Web site of each of the aromatase inhibitors
      available in the United States. Identified publications relevant to the article
      objectives were selected. RESULTS: Anastrozole, letrozole, and exemestane are the
      3 commercially available aromatase inhibitors approved by the US Food and Drug
      Administration for the treatment of hormone receptor-positive breast cancer in
      postmenopausal women. They have been used in several clinical scenarios,
      including advanced and early disease and chemoprevention, and in the neoadjuvant
      setting. There is evidence that aromatase inhibitors are more effective and
      tolerable than tamoxifen in advanced breast cancer and in the neoadjuvant
      setting. Based on the results of a large, randomized trial, their use in early
      disease and in chemoprevention is also promising. Aromatase inhibitors appear
      safe; however, the long-term safety profile is still unknown, especially
      concerning bone metabolism. CONCLUSION: Third-generation aromatase inhibitors are
      a new treatment modality in estrogen and/or progesterone-receptor positive breast
      cancer. Although they are replacing the "classic" antiestrogen agents used in
      metastatic breast cancer, their benefit in early disease and as chemopreventive
      agents is not completely clear. Ongoing clinical studies should become available
      within the next few years and will provide additional recommendations for their
      use in patients with breast cancer.

PMID- 15476903
TI  - Dose-ranging analgesic study of Prosorb diclofenac potassium in postsurgical
      dental pain.
AB  - BACKGROUND: ProSorb diclofenac potassium (K) is a novel, liquid-filled rapid
      dispersion formulation of the nonsteroidal anti-inflammatory drug diclofenac,
      placed into soft gelatin capsules. Its time to maximal plasma drug concentration
      has been shown to be approximately half, and its maximal plasma drug
      concentration nearly twice, that of immediate-release diclofenac K tablets.
      OBJECTIVE: This study compared the analgesic dose-response relationship and
      tolerability of 3 doses of ProSorb diclofenac K and placebo in the treatment of
      pain after dental impaction surgery. METHODS: This randomized, double-blind,
      double-dummy, placebo-controlled parallel-group study was conducted at 6 centers
      across the United States. Patients aged 18 to 65 years with moderate or severe
      pain after the removal of > or =1 impacted mandibular third molar were randomly
      assigned to receive a single dose of ProSorb diclofenac K 25, 50, or 100 mg or
      placebo. Pain intensity and relief were assessed up to 6 hours after dosing.
      Rescue treatment was allowed after 1 hour. Efficacy end points included the
      summed pain intensity difference over 3 and 6 hours (SPID3 and 6); total pain
      relief at 3 and 6 hours (TOTPAR3 and 6); median times to onset of perceptible and
      meaningful relief (analgesic onset) and rescue medication use (analgesic
      duration); and cumulative percentage of patients using rescue medication.
      Tolerability was assessed using vital sign measurements and spontaneous reporting
      of adverse events. RESULTS: A total of 265 patients (154 women, 111 men; mean
      age, 23.3 years) were enrolled. All 3 ProSorb diclofenac K groups showed higher
      SPID6 and TOTPAR6 scores and longer median times to rescue medication use than
      the placebo group (all, P < 0.001). For these end points, a dose-response
      relationship was evident between the 100-mg dose and the 25- and 50-mg doses (P <
      or = 0.05); the 25- and 50-mg doses were similar. In the diclofenac groups,
      median onset times for first perceptible (< or =22.5 min) and meaningful (< or
      =53.0 min) relief were significantly more rapid than placebo (P < or = 0.01).
      Proportions of patients requiring rescue analgesic were < or =50.8% with
      diclofenac compared with 79.4% with placebo. Proportions of patients assigning a
      global evaluation of good or better was > or =68% with diclofenac compared with
      21% for placebo. Tolerability was similar across all treatment groups.
      CONCLUSION: In this study of patients treated for pain following dental impaction
      surgery, single doses of ProSorb diclofenac K 25, 50, and 100 mg were more
      efficacious than placebo with respect to reduction of pain. All 3 doses provided
      a rapid analgesic onset and were well tolerated.

PMID- 15476904
TI  - Comparison of the effects of telmisartan and nifedipine gastrointestinal
      therapeutic system on blood pressure control, glucose metabolism, and the lipid
      profile in patients with type 2 diabetes mellitus and mild hypertension: a 12
      month, randomized, double-blind study.
AB  - BACKGROUND: Angiotensin receptor blockers (ARBs) provide effective blood pressure
      control. Whereas none of the ARBs appear to affect glucose homeostasis, some ARBs
      have been associated with a decrease in cholesterolemia. OBJECTIVE: This study
      was conducted to evaluate blood pressure control glucose homeostasis, and the
      plasma lipid profile in patients with type 2 diabetes mellitus and mild
      hypertension during 12 months of treatment with the ARB telmisartan or nifedipine
      gastrointestinal therapeutic system (GITS). METHODS: In this double-blind trial,
      patients taking oral hypoglycemic agents were randomized to receive telmisartan
      40 mg or nifedipine GITS 20 mg once daily for 12 months. At the time of
      enrollment, patients were given advice on diet (1400-1600 kcal/d) and exercise
      (stationary bicycle for > or =30 min, 4 d/wk). Assessments of systolic blood
      pressure (SBP), diastolic blood pressure, body mass index (BMI), fasting plasma
      glucose concentrations, glycosylated hemoglobin, fasting plasma insulin
      concentrations, the homeostasis model assessment of insulin resistance, and the
      lipid profile were performed at baseline and after 6 and 12 months of treatment.
      RESULTS: One hundred sixteen patients were divided into 2 age- and sex-matched
      treatment groups (58 men, 58 women; mean [SD] age, 52.5 [5] years). All patients
      were in good general health at baseline; had achieved adequate glycemic control
      with diet and oral hypoglycemic agents; were taking antihypercholesterolemic
      drugs; and had no evidence of macroangiopathy, microalbuminuria, or neuropathy.
      There were significant reductions from baseline in seated trough SBP after 12
      months of treatment with both telmisartan and nifedipine GITS (from 139 [4] to
      132 [4] mm Hg and from 140 [4] to 130 [4] mm Hg, respectively; both, P < 0.01).
      No change in BMI or glucose metabolism was observed with either treatment. After
      12 months, there were significant improvements in concentrations of total
      cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) with telmisartan
      (-9% and -11.5%, respectively; both, P < 0.01) compared with nifedipine GITS (-2%
      and -1.5%). CONCLUSIONS: In this selected sample of patients with type 2 diabetes
      and mild hypertension, both telmisartan and nifedipine GITS produced significant
      reductions in blood pressure. Telmisartan was associated with a slight but
      statistically significant improvement in plasma TC and LDL-C concentrations
      compared with nifedipine GITS.

PMID- 15476905
TI  - Clinical efficacy of olopatadine hydrochloride ophthalmic solution 0.2% compared
      with placebo in patients with allergic conjunctivitis or rhinoconjunctivitis: a
      randomized, double-masked environmental study.
AB  - BACKGROUND: Previous studies have suggested that olopatadine hydrochloride
      ophthalmic solution 0.2% administered once daily is effective for up to 24 hours
      after instillation and is well tolerated in adults and children aged > or =3
      years. OBJECTIVE: The goal of this study was to evaluate the efficacy and safety
      profile of olopatadine 0.2% compared with placebo in patients with seasonal
      allergic conjunctivitis or rhinoconjunctivitis. METHODS: This was a 10-week,
      randomized, placebo-controlled, double-masked environmental study conducted
      during the spring allergy season (April-August) of 2003. Patients assessed their
      ocular signs and symptoms in terms of frequency (whole-unit scale from 0 to 5)
      and severity (half-unit scale from 0 to 4), and grass pollen counts were obtained
      daily for each investigative site. Responder analyses were conducted by pollen
      level (frequency based) and pollen period (severity based) to evaluate the
      clinical significance of differences in ocular itching and redness between
      treatment groups. RESULTS: Two hundred sixty patients (137 females, 123 males)
      were enrolled in the study, including 28 children aged between 11 and 17 years;
      the overall population was 74% white, 11% black, 4% Hispanic, and 11% other. The
      frequency-based responder analyses of ocular itching and redness showed that when
      grass pollen counts were high (>20 gr/m(3) air), a respective 21% and 14% of
      patients in the olopatadine 0.2% group assessed the frequency of ocular itching
      and redness as >2, compared with 47% and 31% of patients in the placebo group (P
      < 0.001 for ocular itching; P < 0.003 for redness). The results of the severity
      based responder analyses by peak pollen period were consistent with those of the
      frequency-based analyses. Compared with placebo, olopatadine 0.2% was associated
      with significant reductions in calculated mean scores for ocular itching and
      redness by pollen level and by pollen period. No patient was discontinued from
      the study because of a treatment-related adverse event, and no patient
      experienced a treatment-related serious adverse event. CONCLUSION: In the
      patients studied, olopatadine 0.2% appeared to be effective and well tolerated
      when administered once daily for the treatment of the ocular signs and symptoms
      of allergic conjunctivitis or rhinoconjunctivitis.

PMID- 15476906
TI  - Effects of valdecoxib in the treatment of chronic low back pain: results of a
      randomized, placebo-controlled trial.
AB  - BACKGROUND: Valdecoxib, a cyclooxygenase (COX)-2 specific inhibitor, is indicated
      for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis, and
      primary dysmenorrhea. Therapeutic doses of COX-2 specific inhibitors are as
      effective as nonspecific nonsteroidal anti-inflammatory drugs in reducing
      inflammatory pain while sparing the gastrointestinal and platelet toxicity
      associated with nonspecific COX-1 inhibition. OBJECTIVE: The aim of this study
      was to assess the analgesic efficacy and tolerability of valdecoxib 40 mg/d
      compared with placebo in the treatment of chronic low back pain. METHODS: This 4
      week, prospective, randomized, double-blind placebo-controlled, parallel-group
      study was conducted at 37 centers across the United States and 5 centers in
      Canada. Patients aged > or =18 years with chronic low back pain in flare were
      enrolled. Patients were randomized to receive valdecoxib 40-mg/d or placebo
      tablets, once daily for 4 weeks. Patients rated low back pain intensity on a
      visual analog scale and completed the Roland-Morris Disability Questionnaire and
      the modified Brief Pain Inventory-Short Form (mBPI-SF) at each visit. RESULTS:
      Two hundred ninety-three patients were enrolled. The valdecoxib group comprised
      148 patients (81 women, 67 men; mean [SD] age, 48.6 [13.3] years; mean [SD] body
      weight, 86.6 [20.9] kg), and the placebo group included 145 patients (85 women,
      60 men; mean [SD] age, 48.7 [12.6] years; mean [SD] body weight, 85.6 [19.9] kg).
      Of the enrolled patients, 249 completed the study: 134 patients (91%) who
      received valdecoxib and 115 patients (79%) who received placebo. No statistically
      significant differences in patient baseline characteristics were noted between
      treatment groups, except in response to 1 mBPI-SF question; patients in the
      valdecoxib group reported significantly greater interference in relations with
      other people due to pain than did those in the placebo group (P = 0.048). Changes
      from baseline in low back pain intensity were significantly greater in valdecoxib
      treated patients at each assessment (all, P < 0.001 vs placebo). Pain scores on
      the mBPI-SF indicated significantly greater pain relief with valdecoxib at each
      assessment (all, P < or = 0.014 vs placebo). Improvements in mean Roland-Morris
      Disability Questionnaire score with valdecoxib were significantly greater than
      with placebo at each assessment (all, P < or = 0.003). Although the overall
      incidence of adverse events (AEs) was significantly higher among patients
      receiving valdecoxib than those receiving placebo (35.1% vs 24.1%, respectively;
      P = 0.042), no significant differences were found between groups for the
      incidence of any individual AE. Most AEs (89% [77/87 total events]) were mild or
      moderate in severity. CONCLUSIONS: In this study of patients with chronic low
      back pain, valdecoxib 40 mg/d provided rapid relief (within 1 week) and
      consistent relief (over 4 weeks). In addition, significant improvement in
      function and decreased disability were found with valdecoxib compared with
      placebo.

PMID- 15476907
TI  - In vitro effects of risperidone and 9-hydroxy-risperidone on human platelet
      function, plasma coagulation, and fibrinolysis.
AB  - BACKGROUND: Thrombotic events have been reported with the use of antipsychotic
      compounds, although the incidence, predisposing factors, and biological
      mechanisms associated with these events in psychiatric patients are subject to
      debate. OBJECTIVE: The in vitro actions of risperidone and its active metabolite
      9-hydroxy-risperidone (9-OH-risperidone) on human platelet function, plasma
      coagulation, and fibrinolysis were examined to explore whether hematologic
      effects might be a mechanism for thrombotic events with these compounds. METHODS:
      Blood was donated by healthy white male subjects who were free of medications
      (particularly acetylsalicylic acid and nonsteroidal anti-inflammatory compounds).
      Platelet shape change and adhesion/aggregation reactions to risperidone and 9-OH
      risperidone induced by adenosine diphosphate (ADP), collagen, epinephrine, and 5
      hydroxytryptamine (5-HT) were tested in human platelet-rich plasma. Arachidonic
      acid metabolism was assessed in human platelets and rat aortic rings. Plasma
      coagulation was tested in human platelet-poor plasma. Fibrinolysis was measured
      in human whole blood. RESULTS: The 12 study subjects ranged in age from 20 to 40
      years (median age 30 years). At concentrations of 1 x 10(-5) mol/L (approximately
      4180 ng/mL), neither risperidone nor 9-OH-risperidone induced platelet shape
      change or aggregation, amplified reactions to ADP, or modified platelet
      adhesion/aggregation induced by collagen or ADP, but they did attenuate
      epinephrine-induced platelet aggregation (-50% in the case of 9-OH-risperidone; P
      < 0.05) and 5-HT-induced platelet aggregation (drug concentrations yielding 50%
      inhibition of 5-HT-induced platelet aggregation, 0.5 and 0.2 ng/mL,
      respectively). Cyclooxygenase, thromboxane A2 synthase, 12-lipoxygenase,
      prostacyclin synthase, plasma coagulation, and fibrinolysis were unaffected.
      CONCLUSIONS: Risperidone and 9-OH-risperidone reduced epinephrine- and 5-HT
      induced human platelet aggregation but did not significantly alter other measures
      of platelet function, plasma coagulation, or fibrinolysis in vitro.

PMID- 15476908
TI  - Comparison of topical tobramycin-dexamethasone with dexamethasone-neomycin
      polymyxin and neomycin-polymyxin-gramicidin for control of inflammation after
      cataract surgery: results of a multicenter, prospective, three-arm, randomized,
      double-masked, controlled, parallel-group study.
AB  - BACKGROUND: Intraocular inflammation is typically treated with a combination of
      anti-inflammatory and anti-infective drugs. Tobramycin-dexamethasone (TD) has not
      been associated with any serious adverse events, indicating good tolerability.
      OBJECTIVE: The aims of this study were the following: (1) to demonstrate
      noninferiority of TD compared with dexamethasone-neomycin-polymyxin (DNP) in
      terms of anti-inflammatory efficacy, (2) to compare the anti-inflammatory
      efficacy of TD and DNP with that of a "placebo" control (antibiotic without anti
      inflammatory agent), and (3) to provide additional safety data on TD. METHODS:
      This prospective, double-masked, parallel-group study was conducted at 22
      ophthalmology clinics across Europe and Brazil. Patients aged > 18 years
      undergoing cataract surgery were randomly assigned, in a 2:2:1 ratio, to receive
      tobramycin 3 mg/mL plus dexamethasone 1 mg/mL, dexamethasone 1 mg/mL plus
      neomycin sulfate 3500 IU/mL plus polymyxin B sulfate 6000 IU/mL, or neomycin
      sulfate 3500 IU/mL plus polymyxin B sulfate 7500 IU/mL plus gramicidin 20
      microg/mL. All treatments were given as 1 drop instilled in the operated eye
      q.i.d. for 21 days. The primary efficacy end point, intraocular inflammation
      (determined using the sum of scores on anterior chamber cells and aqueous flare),
      was assessed at days 3, 8, 14, and 21 after surgery. RESULTS: A total of 271
      patients were enrolled (158 women, 113 men; age range 42-90 years) (TD, 104
      patients; DNP, 110 patients; and neomycin-polymyxin-gramicidin [NPG], 57
      patients). Intraocular inflammation was similar in the TD and DNP groups at all
      time points. At days 8, 14, and 21, inflammation scores were significantly lower
      with TD than with NPG (all, P < 0.05). At day 8, the inflammation score was
      significantly lower with DNP than with NPG (P < 0.05). A greater number of
      patients receiving NPG experienced treatment-related ocular allergic reactions
      compared with patients receiving TD (P < 0.05). One patient receiving TD (1.0%)
      and 5 given NPG (9.0%) were withdrawn due to ocular allergic reactions. None of
      the patients experienced an increase in intraocular pressure > or =10 mm Hg from
      baseline. CONCLUSIONS: In this study of patients undergoing cataract surgery
      combination therapy with TD was noninferior to DNP and was well tolerated.

PMID- 15476909
TI  - Randomized, double-blind comparison of subhypnotic-dose propofol alone and
      combined with dexamethasone for emesis in parturients undergoing cesarean
      delivery.
AB  - BACKGROUND: Nausea, retching, and vomiting are common in parturients undergoing
      cesarean delivery performed under regional anesthesia. Subhypnotic-dose propofol
      1.0 mg/kg per hour has been used to reduce the incidence of these emetic
      symptoms. Dexamethasone has been shown to reduce chemotherapy-induced emesis when
      added to an antiemetic regimen. OBJECTIVE: The aim of this study was to examine
      the difference in efficacy and tolerability between subhypnoticdose propofol 1.0
      mg/kg per hour alone and combined with dexamethasone 8 mg for reducing
      postdelivery emetic episodes in parturients undergoing cesarean delivery.
      METHODS: In a randomized, double-blind trial, parturients received IV placebo
      (saline) or dexamethasone 8 mg followed by a continuous infusion of propofol at
      subhypnotic dose (1.0 mg/kg per hour) immediately after clamping of the umbilical
      cord. Intraoperative, postdelivery emetic episodes and safety assessments were
      performed by an investigator. RESULTS: One hundred twenty parturients (mean [SD]
      age, 29 [5] years; age range, 21-38 years; mean [SD] height, 158 [7] cm; height
      range, 145-172 cm; mean [SD] body weight, 72 [8] kg; weight range, 54-90 kg) were
      enrolled in the study, 60 in each treatment group. The treatment groups were
      comparable with respect to maternal demographics and operative management. The
      rate of emetic symptoms (nausea, retching, and vomiting) in an intraoperative,
      postdelivery period was lower in patients who received the combination regimen
      than in those who received subhypnotic-dose propofol 1.0 mg/kg per hour alone (5%
      [3/60] vs 20% [12/60], respectively; P = 0.012). No clinically important adverse
      events attributable to the study drug were observed in either group. CONCLUSION:
      In the parturients undergoing cesarean delivery performed under spinal anesthesia
      in this study, the combination of subhypnotic-dose propofol 1.0 mg/kg per hour
      and dexamethasone 8 mg was more effective than propofol alone for reducing the
      incidence of postdelivery emetic symptoms.

PMID- 15476910
TI  - Randomized, controlled, parallel-group comparison of ambulatory and clinic blood
      pressure responses to amlodipine or enalapril during and after treatment in adult
      chinese patients with hypertension.
AB  - BACKGROUND: Few studies have examined the relative efficacy and tolerability of
      antihypertensive drug classes in Chinese populations. OBJECTIVE: This study
      compared the efficacy, tolerability, and duration of antihypertensive effect of
      amlodipine besylate and enalapril in Chinese patients with hypertension,
      including elderly patients with isolated systolic hypertension. METHODS: This
      randomized, double-blind, double-dummy, parallel-group dose-titration study was
      conducted at the Department of Medicine and Therapeutics, Chinese University of
      Hong Kong. Chinese patients aged 18 to 80 years with primary hypertension were
      enrolled. After a 4-week placebo run-in period, patients were randomly assigned
      to receive active oral, once-daily treatment with amlodipine (5 mg) or with
      enalapril (5 mg) for 14 weeks. Treatment doses were titrated at weeks 4 and 8 if
      necessary according to blood pressure (BP) response and if the dose had been
      tolerated. Patients also underwent 24-hour ambulatory BP monitoring (ABPM) at the
      end of the placebo run-in, after the first and last doses of active treatment,
      and 48 hours after discontinuation of treatment to determine the duration of drug
      action and to mimic the effect of 2 missed doses. RESULTS: Eighty patients were
      recruited for the study (26 men, 54 women; mean [SD] age, 60.5 [11.6] years) (40
      patients per group). Thirty-seven patients in each group completed the active
      treatment phase. Baseline trough BPs were similar: 167.7 (15.0)/94.6 (9.7) mm Hg
      in the amlodipine group and 168.6 (11.9)/93.4 (9.5) mm Hg in the enalapril group.
      After 14 weeks of treatment, amlodipine (mean [SD] final dose, 6.3 [2.3] mg)
      produced greater reductions than enalapril (mean [SD] final dose, 13.3 [6.6] mg)
      in trough BP (-20.8 [13.2]/-9.2 [9.0] vs -5.5 [14.9]/-3.2 [10.6] mm Hg,
      respectively; P < or = 0.01). Most of the effect of amlodipine persisted for 72
      hours after the last dose (-18.9 [14.6]/-11.1 [11.7] mm Hg), but enalapril had no
      significant antihypertensive effect at 72 hours (-1.3 [12.3]/-1.8 [9.1] mm Hg).
      Similar observations were found with ABPM recordings. Cough was reported in 5
      patients (12.5%) and 13 patients (32.5%) in the amlodipine and enalapril groups,
      respectively, but was thought to be treatment related in only 6 patients (15.0%),
      all in the enalapril group. One of the patients in the enalapril group withdrew
      from the study because of cough, and 1 patient in the amlodipine group withdrew
      because of ankle edema.

PMID- 15476911
TI  - French guidelines for the diagnosis and management of migraine in adults and
      children.
AB  - BACKGROUND: The French Recommendations for Clinical Practice: Diagnosis and
      Therapy of Migraine are guidelines concerning the overall management of patients
      with migraine, including diagnostic and therapeutic strategies and assessment of
      disability. OBJECTIVE: This article summarizes the guidelines as they apply to
      adults and children, and proposes future direction for steps toward optimal
      treatment of migraine in patients in France. METHODS: The recommendations were
      categorized into 3 levels of proof (A-C) according to the National Agency for
      Accreditation and Evaluation in Health (ANAES) methodology and were based on a
      professional consensus reached among members of the Working Group and the
      Guidelines Review Group of the ANAES. RESULTS: The International Headache Society
      diagnostic criteria for migraine should be used in routine clinical practice.
      Recommended agents for the treatment of migraine in adults include nonsteroidal
      anti-inflammatory drugs, acetylsalicylic acid (ASA) monotherapy or in combination
      with metoclopramide, acetaminophen monotherapy, triptans, ergotamine tartrate,
      and dihydroergotamine mesylate. Patients should use the medication as early as
      possible after the onset of migraine headache. For migraine prophylaxis in
      adults, the following can be used: propranolol, metoprolol, oxetorone, or
      amitriptyline as first-line treatment, and pizotifen, flunarizine, valproate
      sodium, or topiramate as second-line treatment. Migraine in children can be
      distinguished from that in adults by shorter duration (2-48 hours in children
      aged <15 years), more frequent bilateral localization, frequent predominant
      gastrointestinal disturbances, and frequent pallor hailing the onset of the
      attack. The following drugs are recommended in children and adolescents:
      ibuprofen in children aged >6 months, diclofenac in children weighing >16 kg,
      naproxen in children aged >6 years or weighing >25 kg, ASA alone or in
      combination with metoclopramide, acetaminophen alone or in combination with
      metoclopramide, and ergotamine tartrate in children aged >10 years. CONCLUSIONS:
      These guidelines are intended to help general practitioners to manage migraine
      patients according to the rules of evidence-based medicine.

PMID- 15476912
TI  - Cisplatin-induced hypokalemic paralysis.
AB  - INTRODUCTION: Profound hypokalemic conditions resulting from cisplatin therapy
      have been known to produce hypokalemic paralysis in rare cases. We describe such
      a case of cisplatin-induced hypokalemic paralysis. CASE SUMMARY: A 15-year-old
      Persian girl with ovarian dysgerminoma presented with severe generalized weakness
      and paraplegia 1 week after the fourth course of cisplatin-based chemotherapy. On
      physical examination, there was symmetric flaccid paralysis and areflexia in all
      of the extremities and particularly in the lower limbs. Her serum potassium
      concentration was 1.7 mmol/L. Metastatic disease was excluded by a comprehensive
      systemic evaluation. Complete clinical and paraclinical recovery was achieved
      after short-term administration of potassium supplement. DISCUSSION: Adverse drug
      reactions are common with cisplatin, but the drug is only rarely associated with
      hypokalemic paralysis. Based on the Naranjo causality algorithm, an objective
      assessment revealed cisplatin to be a probable cause of hypokalemic paralysis in
      this case. This adverse drug event--whether isolated or secondary to
      hypomagnesemia--may be deceptive, leading to a fatal mistake in the oncology
      setting, and should therefore be precisely differentiated from cancer-related
      complications. CONCLUSIONS: This case suggests that cisplatin should be added to
      the list of agents causing hypokalemic paralysis. Regular serum electrolyte
      measurement, the early detection of cation deficiency, and appropriate
      replacement of cations are all recommended.

PMID- 15476914
TI  - Pharmaceutical pricing, price controls, and their effects on pharmaceutical sales
      and research and development expenditures in the European Union.
AB  - BACKGROUND: Each country in the European Union (EU) currently employs direct
      price controls or permutations of direct price controls, such as reference
      pricing or limitations on returns to capital. Some countries also use volume
      controls. A new proposal that is being discussed would have all of the countries
      in the EU adopt uniform pricing for each pharmaceutical. OBJECTIVE: This paper
      analyzes the economic effects of free-market pricing individual-country price
      controls, and uniform EU price controls. METHODS: Microeconomic and mathematical
      models were used to simulate and predict probable economic outcomes in a
      comparative static setting. RESULTS: Price controls may be in the form of price
      ceilings or price floors. Both forms of price control generate deadweight
      economic losses in the short run and long run. A uniform EU price for each
      pharmaceutical sold there would have elements of a price ceiling in some of the
      countries and of a price floor in other countries. The deadweight loss incurred
      would be a function of the level at which the uniform price was set by the EU and
      the price elasticity of demand for each pharmaceutical in each country.
      CONCLUSIONS: Economic efficiency is maximized in both the short run and long run
      when prices are set in freely competitive markets. An additional important
      dimension of Ramsey pricing within a competitive context is that it generates
      funds for investment in pharmaceutical research and development, which enhances
      economic efficiency in the long run.

PMID- 15476915
TI  - The use of disease-modifying new drugs for multiple sclerosis treatment in
      private-sector health plans.
AB  - OBJECTIVES: The aims of this study were to estimate the effects of demographics,
      location, severity of multiple sclerosis (MS), comorbidities, plan type,
      coinsurance levels, and time of entry into the sample on the use of disease
      modifying agents. METHODS: A retrospective analysis of medical claims data from
      1996 through 2000 was conducted with a sample of MS patients covered by self
      insured, employer-sponsored health plans. Proportional hazard analysis with the
      SAS procedure for proportional hazards regression was used to estimate the impact
      of the factors of interest on the use of disease-modifying agents. A simulation
      was conducted to assess the impact of changing drug copayments on the use of
      disease-modifying agents for MS. RESULTS: The sample included 1807 patients.
      Patients were followed for as long as possible, but most were observed for <3
      years; the mean (SD) follow-up time was 972.88 (440.59) days. Most factors
      associated with the use of disease-modifying agents were immutable. They included
      the following: high severity of illness (only marginally related; P = NS);
      history of seizures (P = 0.03), depression (P < 0.01), or heart disease (P =
      0.01); census region of location (P < 0.01); union membership or association with
      a union member (P < 0.01); drug copayment requirements (P < 0.05); and year of
      entry into the sample (P < 0.01). In the simulation, a 50% reduction in drug
      copayments was associated with an increase of the proportion of patients treated
      with disease-modifying drugs from 41.2% to 54.7%. Patients' and physicians'
      preferences for treatment could not be measured directly. The true onset of MS
      may be unknown for many patients, but this would be the case even if medical
      records or other data were used for this study. CONCLUSIONS: Our analyses showed
      an association between copayments and the use of disease-modifying drugs for MS.
      Insurance policies can be tailored to influence the use of disease-modifying
      drugs, enhancing the quality of care for MS patients and reducing price-related
      barriers to beneficial treatment. Future research should test whether reducing
      copayments for MS treatment would reduce the use of other health care services
      (via better MS treatment that modifies the course of illness), or whether the use
      of disease-modifying drugs would increase total costs to the plan, resulting in
      slightly higher premiums.

PMID- 15476917
TI  - Plant perception systems for pathogen recognition and defence.
AB  - Recognition of and defence against microbial infections are universal adaptations
      of multicellular organisms. Plants express a sophisticated molecular system for
      recognition of and response to potentially pathogenic microorganism. Although the
      environments of plant and animal cells are vastly different and present unique
      challenges to invading pathogens, the molecular basis of the innate immune
      response shows remarkable evolutionary conservation in both kingdoms. Even if
      more cellular components are continually being identified in plants, the
      mechanism, interactions and responses are only partly understood. Furthermore,
      most of this research has been performed in the model plant Arabidopsis thaliana
      and a significant effort will be needed to understand the above processes in crop
      species and in natural populations. In this review I will describe examples of
      the best characterized recognition systems in plants, that mediate pathogen
      perception either through the perception of highly variable and non-essential
      pathogen molecules or via conserved microbial structures called pathogen
      associated molecular patterns (PAMPs).

PMID- 15476918
TI  - Infectious non-self recognition in invertebrates: lessons from Drosophila and
      other insect models.
AB  - The vertebrate innate immune system recognizes infectious non-self by employing a
      set of germline-encoded receptors such as nucleotide-binding oligomerisation
      domain proteins (NODs) or Toll-like receptors (TLRs). These proteins are involved
      in the recognition of various microbial-derived molecules, including
      lipopolysaccharide (LPS), peptidoglycan (PGN) and beta1,3-glucan. Drosophila Toll
      receptors are not directly dedicated to non-self recognition and insect NOD
      orthologues have not yet been identified. Studies started more than 20 years ago
      and conducted on different insect models have identified other receptors on which
      invertebrate innate systems rely to sense invading microorganisms.

PMID- 15476919
TI  - Recognition strategies in the innate immune system of ancestral chordates.
AB  - Many components of the innate immune system in vertebrates can be reliably traced
      to urochordates and successful strategies for the detection and elimination of
      pathogens are present at that level of animal evolution, but the issue of where
      and how the adaptive immune system emerged is still obscure. There is a paucity
      of evidence for a gradual transition from the innate immune system of
      invertebrates to the recombinatorial immune system of higher vertebrates. None of
      the classical elements of MHC based transplantation immunity (MHC, TCR) or
      humoral immunity (Ig) have been found in urochordates or Agnathans. Nevertheless
      there is abundant evidence for adaptive immune responses in the agnathans. This
      remarkable paradox raises a number of questions. How do these ancestral chordates
      discriminate between the constituents of the external world and the constituents
      of "self"? Are these strategies universal within the animal kingdom and among
      chordates, or are different strategies used by representatives of the different
      taxonomic groups? The current state of our knowledge indicates that the immune
      system of lower chordates is very different from that of cartilaginous fishes.
      Pure homology hunting for vertebrate-specific immuno-relevant molecules in
      invertebrates is therefore of limited value. A more promising approach may
      involve unbiased functional screening methods. To understand better the evolution
      of adaptive immune systems, more comparative data from jawless vertebrates
      (lamprey or hagfish) and a representative of Acrania (e.g. Amphioxus) are clearly
      needed.

PMID- 15476920
TI  - Complement: a unique innate immune sensor for danger signals.
AB  - The complement (C) inflammatory cascade is part of the phylogenetically ancient
      innate immune response and is crucial to our natural ability to ward off
      infection. It has three critical physiologic activities: (i) defending against
      microbial infections by triggering the generation of a membranolytic complex
      (C5b9 complex) at the surface of the pathogen and C fragments (named opsonins,
      i.e., C1q, C3b and iC3b) which interact with C cell surface receptors (CR1, CR3
      and CR4) to promote phagocytosis. Soluble C anaphylatoxins (C4a, C3a and C5a)
      greatly control the local pro-inflammatory response through the chemotaxis and
      activation of leukocytes; (ii) bridging innate and adaptive immunity (essentially
      through C receptor type 2, CR2, expressed by B cells) and (iii) disposing of
      immune complexes and the products of the inflammatory injury (i.e., other danger
      signals, e.g., toxic cell debris and apoptotic corpses) to ensure the protection
      and healing of the host. The regulatory mechanisms of C are finely balanced so
      that, on the one hand, the deposition of C is focused on the surface of invading
      microorganisms and, on the other hand, the deposition of C on normal cells is
      limited by several key C inhibitors (e.g., CD46, CD55 and CD59). Knowledge of the
      unique molecular and cellular innate immunological interactions that occur in the
      development and resolution of pathology should facilitate the design of effective
      therapeutic strategies to fight selectively against intruders.

PMID- 15476921
TI  - The role of Toll-like receptors and Nod proteins in bacterial infection.
AB  - Our understanding of innate immunity in mammals has greatly expanded following
      the discovery of the family of membrane-bound receptors, called the Toll-like
      receptors (TLRs). More recently, the nucleotide-binding oligomerisation domain
      (Nod) molecules, Nod1 and Nod2, which are cytoplasmic surveillance proteins, have
      also been shown to be involved in the innate immune response. These two classes
      of detection molecules, classified as "pattern recognition receptors" (PRRs),
      detect microbial ligands in order to initiate a defense response to fight
      infectious disease. These microbial ligands or "pathogen-associated molecular
      patterns" (PAMPs), detected by TLRs and Nods are often structural components of
      the microorganism that are not subject to much variation. These include such
      factors as lipopolysaccharide (LPS) and peptidoglycan from the cell walls of
      bacteria. In order to understand the role of TLRs and Nod proteins in infectious
      disease in vivo it is important to define the site of interaction between PRRs
      and PAMPS. Additionally, the challenge of mice deficient in the various PRRs in
      natural infection models will help to decipher the contribution of these
      molecules not only in the innate immune response against pathogen infection but
      also how these proteins may instruct the adaptive immune response in order to
      have a tailored immune response against a particular microbe.

PMID- 15476922
TI  - Divergent roles for C-type lectins expressed by cells of the innate immune
      system.
AB  - In recent years there has been increasing interest in the diversity and function
      of carbohydrates present on a range of endogenous mammalian glycoproteins and
      pathogen surfaces. It is clear that carbohydrate structures are not merely
      structural components of the molecules which bear them but are, in many
      instances, a source of information to be decoded by biological systems including
      the immune system. Macrophages and other antigen presenting cells express a
      variety of pattern recognition molecules which allow discrimination between self
      and non-self ligands and are well known for their ability to recognise and
      internalise foreign antigens. The role of carbohydrates as molecular determinants
      of self/non-self has been recognised for many years and a family of proteins
      known as the C-type lectins are implicated as the main players in carbohydrate
      recognition within the immune system. More recently, C-type lectin receptors
      which bind ligands other than carbohydrates have been identified, and there are
      additional receptors which bind both carbohydrate and non-carbohydrate ligands.
      In this review article we seek to shed light on the varied roles of this family
      of receptors, particularly those receptors expressed by antigen presenting cells
      and those with known ligands. We also review more recent data on several members
      of this family.

PMID- 15476924
TI  - Melanin-concentrating hormone signaling systems in fish.
AB  - Melanin-concentrating hormone (MCH) is a cyclic neuropeptide synthesized as a
      preprohormone in the hypothalamus of all vertebrates. This neuropeptide binds to
      G-protein-coupled seven transmembrane receptor(s) to mediate its function. MCH
      was named after its function in teleosts, in which it causes aggregation or
      concentration of melanin granules in melanophores, thus regulating body color.
      The function of central MCH that has attracted most attention is its involvement
      in regulating food intake and energy homeostasis in mammals, a role confirmed
      through a series of experiments, including central administration of MCH or MCH
      receptor blockers, and genetic manipulation of MCH and its receptors. The aim of
      this article is to review the recent data on MCH and MCH receptor signaling
      systems in fish.

PMID- 15476925
TI  - Expression and characterization of melanin-concentrating hormone receptors on
      mammalian cell lines.
AB  - The neuropeptide melanin-concentrating hormone (MCH) is expressed in central and
      peripheral tissues where it participates in the complex network regulating energy
      homeostasis as well as in other physiologically important functions. Two MCH
      receptor subtypes, MCH-R1 and MCH-R2, have been cloned which signal through
      activation of Gi/o/q proteins and hence regulate different intracellular signals,
      such as inhibition of cAMP formation, stimulation of IP3 production, increase in
      intracellular free Ca2+ and/or activation of MAP kinases. Most of the data were
      obtained with cell systems heterologously expressing either of the MCH receptors.
      Fewer reports exist on studies with cell lines which endogenously express MCH
      receptors. Here, we describe human and other mammalian cell lines with which MCH
      receptor activation can be studied under "natural" conditions and we summarize
      the characteristics and signaling pathways of the MCH receptors in the different
      cell systems.

PMID- 15476926
TI  - Properties of rat melanin-concentrating hormone receptor 1 internalization.
AB  - Melanin-concentrating hormone (MCH) is a neuropeptide that plays an important
      role in several physiological processes. It activates two G protein-coupled
      receptors (GPCRs), MCH1R and MCH2R, of which MCH1R seems to be a key regulator of
      food intake. By using HEK293T cells stably transfected with Flag-tagged rat
      MCH1R, we investigated the mechanism underlying the MCH-induced internalization
      pathway, which is important for the desensitization or regulation of the receptor
      response. Quantitative analysis by flow cytometry indicated that the rate of
      MCH1R internalization progressed in a rapid and time-dependent manner during the
      first 30 min, and was partly inhibited by pretreatment with the selective protein
      kinase C (PKC) inhibitor Go6850. Overexpression of dominant-negative beta
      arrestin-2 (284-409) or dynamin I-K44A significantly prevented MCH-induced
      internalization of MCH1R, while overexpression of dominant-negative beta-arrestin
      1-V53D had no effect. A triple-substituted mutant at Thr317, Ser325 and Thr342 to
      Ala residue in the C-terminus significantly prevented MCH-induced receptor
      internalization. Similar extents of internalization prevention were noted with
      the deletion mutants DeltaThr342 and DeltaGlu346, lacking 11 and 7 residues in
      the C-terminal tail, respectively. Our data suggest that MCH1R undergoes rapid
      MCH-induced internalization through a PKC-, beta-arrestin-2- and dynamin I
      dependent pathway and that a portion of the C-terminal tail plays an important
      role in the internalization process.

PMID- 15476927
TI  - Beyond skin color: emerging roles of melanin-concentrating hormone in energy
      homeostasis and other physiological functions.
AB  - Melanin-concentrating hormone (MCH) is a cyclic peptide that mediates its effects
      by the activation of two G-protein-coupled seven transmembrane receptors (MCHR1
      and MCHR2) in humans. In contrast to its primary role in regulating skin color in
      fish, MCH has evolved in mammals to regulate dynamic physiological functions,
      from food intake and energy expenditure to behavior and emotion. Chronic infusion
      or transgenic expression of MCH stimulates feeding and increases adipocity,
      whereas targeted deletion of MCH or its receptor (MCHR1) leads to resistance to
      diet-induced obesity with increased energy expenditure and thermogenesis. The
      involvement of MCH in energy homeostasis and in brain activity has also been
      validated in mice treated with non-peptide antagonists, suggesting that blockade
      of MCHR1 could provide a viable approach for treatment of obesity and certain
      neurological disorders. This review focuses on emerging roles of MCH in
      regulating central and peripheral mechanisms.

PMID- 15476928
TI  - Possible involvement of melanin-concentrating hormone in food intake in a teleost
      fish, barfin flounder.
AB  - We investigated the involvement of MCH in food intake in barfin flounder. The
      structure of barfin flounder MCH was determined by cDNA cloning and mass
      spectrometry. In fasted fish, the MCH gene expression and the number of MCH
      neurons in the brain were greater than controls. In white-reared fish, the MCH
      gene expression and the number of MCH neurons in the brain were greater than
      black-reared fish. Furthermore, white-reared fish grew faster than black-reared
      fish. These results indicate that a white background stimulated production of MCH
      and MCH, in turn, enhanced body growth, probably by stimulating food intake.

PMID- 15476929
TI  - Comparative analysis of melanin-concentrating hormone structure and activity in
      fishes and mammals.
AB  - A comparative analysis of the structure of the melanin-concentrating hormone
      (MCH) precursor reveals that this sequence has been subjected to a higher
      selection pressure in mammals than in teleosts, suggesting that the structural
      constraints have not been the same throughout the vertebrate lineage. In
      contrast, the MCH peptide sequence has been very well conserved in all species. A
      sensitive and reproducible eel skin assay was developed and allowed us to define
      the structural features needed for a full MCH bioactivity. It was shown that the
      minimal structure carrying the critical residues was the same in fishes and in
      mammals. A pharmacological approach confirmed that MCH receptor activation
      decreased the cAMP levels in the fish skin, but this effect appeared to be
      independent from a Galphai protein. We propose that one of the intracellular
      signaling pathways of the MCH receptor in fish skin is the activation of one or
      several cellular phosphodiesterases.

PMID- 15476930
TI  - Intermedin, a novel calcitonin family peptide that exists in teleosts as well as
      in mammals: a comparison with other calcitonin/intermedin family peptides in
      vertebrates.
AB  - Endocrine regulation in vertebrates is critical for the adaptation and regulation
      of homeostasis. The G protein-coupled receptor (GPCR) signaling transduction
      system represents one of the most ancient forms of cell surface signaling.
      Recently, comparative sequence analysis has aided in the identification and
      pairing of a variety of ligand/GPCR signaling systems. Among the ligands of type
      II GPCRs, the calcitonin family peptides including calcitonin, alpha-calcitonin
      gene-related peptide (alphaCGRP), betaCGRP, adrenomedullin, and amylin are among
      the best studied hormones, and the founding member, calcitonin, was originally
      identified and isolated from teleosts. This unique group of peptides shares a
      conserved tertiary structure with an N-terminal disulfide-bridged ring. In
      mammals, these peptides signal through two closely related type II GPCRs and
      three unique receptor activity-modifying proteins. Recently, based on the
      analysis of multiple vertebrate genomes, we identified a novel calcitonin/CGRP
      family peptide named intermedin. Here we show that in humans the five paralogous
      family genes, calcitonin, CGRP, amylin, adrenomedullin, and intermedin, evolved
      before the emergence of modern vertebrates, and that teleost genomes carry
      multiple copies of these co-evolved hormone genes. Sequence comparison showed
      that each of these genes is highly conserved in different vertebrates and that
      multiple copies of these peptides in teleosts could be derived from ancient
      genome duplication and/or lineage-specific intragenic duplications. The present
      article provides an overview of the calcitonin/intermedin family peptides found
      in teleost and mammalian genomes, and describes their putative functions. In
      addition, we demonstrate that one of the intermedin orthologs deduced from the
      pufferfish (Fugu rubripes) genome shares a conserved signaling activity with
      mammalian intermedin. The combined results indicate that the physiology
      associated with each of these family peptides likely evolved during early
      vertebrate evolution and diverged to serve select physiological functions in
      different vertebrates.

PMID- 15476931
TI  - Novel fish-derived adrenomedullin in mammals: structure and possible function.
AB  - Adrenomedullin (AM) has been recognized as a member of the calcitonin (CT)/CT
      gene-related peptide (CGRP) family. However, an independent AM family consisting
      of five paralogous peptides exists in teleost fish. Among them, the peptide named
      AM1 is an ortholog of mammalian AM as determined by the linkage analysis of
      orthologous genes and the presence of proAM N-terminal 20 peptide (PAMP)-like
      sequence in the prosegment. Since the peptides named AM2 and 3 are distinct from
      other members with respect to the precursor sequence, tissue distribution of the
      transcripts, and exon-intron organization, we searched for their mammalian
      orthologs from genome databases, which resulted in an identification of AM2 in
      human, rat, and mouse. AM2 was expressed abundantly in the submaxillary gland,
      kidney, and some vascular and digestive tissues of mice. AM2 injected in vivo
      induced potent cardiovascular and renal effects in mice. In the heart and kidney
      of mice, AM2 was localized in endothelial cells of the coronary vessels and in
      glomeruli and vasa recta, respectively. AM2 increased cAMP accumulation in cells
      expressing human CT receptor-like receptor (CRLR) and one of receptor activity
      modifying proteins (RAMPs), but it was no more potent than CGRP and AM. AM2 was
      also less potent than CT in cells expressing CT receptor and RAMP. There remains
      a possibility that a new AM2-specific receptor or an additional RAMP that enables
      CRLR to be an AM2-specific receptor, exists in mammals.

PMID- 15476932
TI  - Stanniocalcin in terminally differentiated mammalian cells.
AB  - Stanniocalcin (STC) is a glycoprotein hormone originally found in teleost fish,
      where it regulates the calcium/phosphate homeostasis, and protects the fish
      against toxic hypercalcemia. STC was considered an exclusive fish protein, until
      the cloning of cDNA for human (in 1995) and murine (in 1996) STC. We originally
      reported a high constitutive content of STC in mammalian brain neurons, and found
      that the expression of STC occurred concomitantly with terminal differentiation
      of neural cells. Since then, we have investigated the expression of STC in
      relation to terminal cell differentiation also in mammalian hematopoietic tissue,
      and fat tissues. In this review we summarize our findings on STC expression
      during postmitotic differentiation in three different cell systems; in neural
      cells, in megakaryocytes and in adipocytes. We also present findings, suggesting
      that STC plays a role for maintaining the integrity of terminally differentiated
      mammalian cells.

PMID- 15476933
TI  - Stanniocalcin 1 as a pleiotropic factor in mammals.
AB  - Stanniocalcin (STC)1 is the mammalian homologue of STC which was originally
      identified as a calcium/phosphate-regulating hormone in bony fishes. STC1 is a
      homodimeric phosphoglycoprotein with few if any identified unique motifs in its
      structure with the exception of CAG repeats in the 5'-untranslated region. In
      contrast to fish STC which is expressed mainly in the corpuscles of Stannius,
      STC1 is expressed in a wide variety of tissues, but unexpectedly is not detected
      in the circulation under normal circumstances. Thus, STC1 may play an
      autocrine/paracrine rather than a classic endocrine role in mammals. Consistent
      with this, pleiotropic effects of STC1 have been postulated in physiological and
      measured in pathological situations. There is much current interest in
      identifying a specific STC1 receptor and putative signaling pathways to which it
      may be coupled. In this regard, STC1 may regulate intracellular calcium and/or
      phosphate (Pi) levels. In the skeletal system, for example, Pi uptake in bone
      forming osteoblasts via a direct effect of STC1 on expression of the NaPi
      transporter Pit1 may contribute to bone formation. Here we review current
      understanding of the role of STC1 and its possible molecular mechanisms in the
      skeleton and elsewhere.

PMID- 15476934
TI  - Evidence for stanniocalcin and a related receptor in annelids.
AB  - Stanniocalcin (STC) is a prime example of a hormone whose discovery in fish led
      to its subsequent discovery in mammals. STC is considered to be first and
      foremost a vertebrate polypeptide hormone with regulatory effects on ion
      transport, mitochondrial function and steroid hormone synthesis. The gene is
      widely expressed in both fishes and mammals, and the hormone can operate via both
      local and endocrine signaling pathways. In spite of the growing catalogue of
      vertebrate hormones and receptors with homologues in invertebrates, the notion
      that there might be an invertebrate STC homolog has received scant attention to
      date. In the present study, we have provided evidence for STC in annelid worms
      (freshwater leeches). Western blot analysis revealed the presence of two STC
      immunoreactive (STCir) proteins in leech tissue extracts of 100 and 193 kDa.
      These same extracts significantly lowered the rate of gill calcium transport upon
      injection into fish. Similarly, fish STC increased the rate of whole body calcium
      uptake when administered to leeches, and STC receptors of high affinity were
      identified on isolated leech plasma membranes. Two discrete populations of STC
      positive cells were also identified in leeches using antibodies to fish STC and
      fish STC cRNA probes. One of the cell types was confined to the skin. The second
      cell type was confined to the coelomic cavity and identified as an adipose cell,
      which in leeches is a major repository of fat. Collectively, the data constitutes
      compelling evidence for the existence of STC-related proteins and receptors in
      annelids that share structural and functional similarities with those in
      vertebrates.

PMID- 15476935
TI  - Ancient evolution of stress-regulating peptides in vertebrates.
AB  - Recent studies on genomic sequences have led to the discovery of novel
      corticotropin-releasing factor (CRF) type 2 receptor-selective agonists,
      stresscopin (SCP)/urocortin III (UcnIII), and stresscopin-related peptide
      (SRP)/urocortin II (UcnII). In addition, analyses of vertebrate genomes showed
      that the CRF peptide family includes four distinct genes, CRF,
      urocortin/urotensin I, SCP/UcnIII, and SRP/UcnII. Each of these four genes is
      highly conserved during evolution and the identity between mammalian and teleost
      orthologs ranges from >96% for CRF to >55% for SCP. Phylogenetic studies showed
      that the origin of each of these peptides predates the evolution of tetrapods and
      teleosts, and that this family of peptide hormones evolved from an ancestor gene
      that developed the CRF/urocortin and SCP/SRP branches through an early gene
      duplication event. These two ancestral branches then gave rise to additional
      paralogs through a second round of gene duplication. Consequently, each of these
      peptides participates in the regulation of stress responses over the 550 million
      years of vertebrate evolution. The study also suggested that the fight-or-flight
      and stress-coping responses mediated mainly by CRF types 1 and 2 receptors
      evolved early in chordate evolution. In addition, we hypothesize that the CRF/CRF
      receptor signaling evolved from the same ancestors that also gave rise to the
      diuretic hormone/diuretic hormone receptors in insects. Thus, a complete
      inventory of CRF family ligands and their receptors in the genomes of different
      organisms provides an opportunity to reveal an integrated view of the physiology
      and pathophysiology of the CRF/SCP family peptides, and offers new insights into
      the evolution of stress regulation in vertebrates.

PMID- 15476936
TI  - Physiological roles of urocortins, human homologues of fish urotensin I, and
      their receptors.
AB  - Urocortin 1, a human homologue of fish urotensin I, together with its related
      compounds (urocortins 2 and 3), comprises a distinct family of stress peptides.
      Urocortin 1 has a high affinity for both corticotropin-releasing factor (CRF)
      type 1 receptor (CRF1) and CRF type 2 receptor (CRF2), and urocortins 2 and 3
      have a high affinity for CRF2, while CRF has a low affinity for CRF2 and a high
      affinity for CRF1. These differences of the binding affinity with receptors make
      the biological actions of these peptides. Besides the binding affinity with
      receptors, the limited overlap of the distribution of CRF and urocortins may also
      contribute to the differences of physiological roles of each peptide. Urocortins
      show 'stress-coping' responses such as anxiolysis and dearousal in the brain. In
      the periphery, recent studies show the potent effects of urocortins on the
      cardiovascular and immune systems. In this review article, we take a look over
      the series of peptides included in this family, especially in terms of the
      versatility of biological actions, along with the various characters of the
      receptors.

PMID- 15476937
TI  - Effects of urocortin 2 and 3 on motor activity and food intake in rats.
AB  - Urocortin 2 (Ucn 2) and Ucn 3 are new members of the corticotropin-releasing
      factor (CRF) family and bind selectively to the CRF type 2 receptor (CRF2). The
      effects of these peptides on behavioral changes induced by CRF were examined in
      rats. In a familiar environment, intracerebroventricular injection of Ucn 2
      attenuated the stimulatory effect of CRF on motor activity, although it alone
      produced no effect. Ucn 3 suppressed motor activity and attenuated the
      stimulatory effect of CRF. In an open field, CRF decreased locomotion and rearing
      but increased grooming behavior. Ucn 2 attenuated the inhibition of locomotor
      activity induced by CRF without affecting other activities, such as rearing or
      grooming behavior. Ucn 3 had no effect on the behavioral changes induced by CRF,
      although it alone decreased locomotion and rearing in a manner similar to CRF.
      Ucn 2 was thus found to have an antagonistic effect on bi-directional motor
      activation induced by CRF, while Ucn 3 had a suppressive effect on motor
      activity. Both Ucn 2 and Ucn 3 suppressed food intake in freely-fed rats, but not
      immediately after injection. These results suggest that the CRF2 receptor is
      involved in motor suppressive effects as well as anxiolytic and anorectic effects
      of Ucn 2 and Ucn 3.

PMID- 15476938
TI  - Urocortins and corticotropin releasing factor type 2 receptors in the
      hypothalamus and the cardiovascular system.
AB  - In addition to urocortin (Ucn I), Ucn II and Ucn III were identified as
      endogenous ligands for corticotropin-releasing factor type 2 receptor (CRF2
      receptor). CRF2 receptor is abundantly located in central hypothalamic
      ventromedial nucleus (VMH) and in peripheral cardiovascular system. In this mini
      review, we focused on the roles of these urocortins and CRF2 receptor in the
      hypothalamus and the cardiovascular system. Ucn II mRNA was increased in the
      parvocellular part or the magnocellular part of the hypothalamic paraventricular
      nucleus (PVN) following immobilization stress or 3 days of water deprivation,
      respectively. Therefore, it is thought that Ucn II may modulate CRF and
      vasopressin synthesis in the PVN in a paracrine or autocrine fashion through PVN
      CRF2 receptor. The early and later phases of Ucn I-mediated feeding suppression
      may be CRF1 and CRF2 receptor-mediated events, respectively. Ucn II decreases
      food intake at a later phase, beyond 4 h post injection. A large dose of
      corticosterone increased plasma leptin and insulin levels as well as the levels
      of CRF2 receptor mRNA. Adrenalectomy, starvation, and immobilization each lowered
      plasma leptin and insulin levels and were associated with decrements in CRF2
      receptor mRNA levels in the VMH. Peripheral injection of leptin increased VMH
      CRF2 receptor mRNA, as can induce reductions of food intake and body weight,
      indicating that circulating leptin is involved in the regulation of VMH CRF2
      receptor mRNA expression. Therefore, it is also plausible that VMH CRF2 receptor
      transduces the anorexogenic effects of leptin as well as those of urocortins. The
      systemic administration of Ucn II decreases mean arterial pressure (arterial
      vascular tone) and causes tachycardia via vascular CRF2 receptor in rats, similar
      to the effects of Ucn I. Thus, CRF2 receptor seems to mediate cardioprotective
      effects of urocortins.

PMID- 15476939
TI  - Urocortins as cardiovascular peptides.
AB  - Urocortins (Ucn) 1, 2 and 3, human homologues of fish urotensin I, form the
      corticotropin-releasing factor (CRF) family, together with CRF, urotensin I and
      sauvagine. Ucn 3 is a novel member of this family and is a specific ligand for
      CRF type 2 receptor. CRF type 2 receptor is thought to mediate the stress-coping
      responses, such as anxiolysis, anorexia, vasodilatation, a positive inotropic
      action on myocardium and dearousal. Endogenous ligands for the CRF type 2
      receptor expressed in the cardiovascular tissues, such as the myocardium, have
      long been unknown. We have shown expression of Ucn 3 as well as Ucn 1 in the
      human heart. Ucn 3 is also expressed in the kidney, particularly distal tubules.
      Studies in various rat tissues showed that high concentrations of immunoreactive
      Ucn 3 were found in the pituitary gland, adrenal gland, gastrointestinal tract,
      ovary and spleen in addition to the brain, heart and kidney. These observations
      suggest that Ucn 3 is expressed in various tissues including heart and kidney,
      and may regulate the circulation in certain aspects of stress and diseases, such
      as inflammation. Ucn 1 and 3 appear to have important pathophysiological roles in
      some cardiovascular diseases.

PMID- 15476940
TI  - Urocortins and the regulation of gastrointestinal motor function and visceral
      pain.
AB  - Urocortin (Ucn) 1, 2 and 3 are corticotropin-releasing factor (CRF)-related
      peptides recently characterized in mammals. Urocortin 1 binds with high affinity
      to CRF type 1 (CRF1) and type 2 (CRF2) receptors while Ucn 2 and Ucn 3 are
      selective CRF2 ligands. They also have a distinct pattern of distribution, both
      in the brain and the gastrointestinal tract, compatible with a role mediating,
      with CRF, the response to stress. In rats and mice, Ucn 1 injected centrally or
      peripherally inhibited gastric emptying and stimulated colonic propulsive motor
      function, mimicking the effects of stress or exogenous CRF. Centrally
      administered Ucn 2 inhibited gastric emptying with similar potency as CRF, while
      Ucn 1 and Ucn 3 were less potent. However, after peripheral administration, Ucn 1
      and Ucn 2 were more potent than CRF. In mice, centrally administered Ucn 1 and 2
      stimulated colonic motility with lower potency than CRF, and Ucn 3 was inactive.
      Studies with selective CRF1 and CRF2 antagonists demonstrated that the gastric
      inhibitory and colonic-stimulatory effects of exogenously administered Ucns are
      mediated through CRF2 and CRF1 receptors, respectively. In addition, Ucn 2 showed
      visceral anti-nociceptive activity associated with the selective activation of
      CRF2 receptors. These observations suggest that, acting centrally and
      peripherally, Ucns might play a significant role in the modulation of
      gastrointestinal motor and pain responses during stress and stress-related
      pathophysiological conditions.

PMID- 15476941
TI  - Localization and physiological roles of urocortin.
AB  - Urocortin, a 40 amino acid peptide, is a corticotropin-releasing factor (CRF)
      related peptide, and can bind to all three types of CRF receptors (CRF type 1,
      type 2a and type 2b receptors) with higher affinities for these receptors than
      CRF. Immunoreactivity of urocortin is widely distributed in central nervous,
      digestive, cardiovascular, reproductive, immune and endocrine systems. Urocortin
      plays important roles in appetite-suppression, immunomodulation, steroidogenesis
      in the ovary, maintenance of the placental function, labor, and cardioprotection
      via CRF receptors. Although urocortin has potent adrenocorticotropin (ACTH)
      releasing activity in vitro, endogenous urocortin does not act on pituitary ACTH
      secretion in vivo.

PMID- 15476942
TI  - Urocortins in human reproduction.
AB  - Data on biological effects and localization of corticotropin-releasing factor
      (CRF), a neuropeptide structurally and biologically related to urocortins, have
      triggered the study on expression of urocortins and their function in human
      reproductive tissues. Ovary, endometrium, placenta and fetal membranes (amnion
      and chorion), myometrium, and prostate are sources of urocortin 1 and, they also
      express urocortin binding sites (receptors and CRF-binding protein), thus
      suggesting that these tissues are also targets of urocortin 1. The current
      concept thus is that urocortin 1 may affect the physiology of human reproduction
      through paracrine/autocrine actions. In particular, in vitro data have shown that
      urocortin 1 plays a major role in human placenta: it stimulates the secretion of
      ACTH, prostaglandins and activin A from cultured human placental cells, and
      regulates placental vessel resistance to blood flow. Furthermore, when incubated
      in myometrial strips, urocortins stimulate uterine contractility, by activating
      specific intracellular pathways. Taken together, these findings do suggest an
      important role of urocortins in the physiology of pregnancy and parturition.

PMID- 15476943
TI  - Urotensin II, a novel peptide in central and peripheral cardiovascular control.
AB  - Urotensin II (UII) is a peptide that was originally isolated and characterized in
      fish. Interest in its effects in mammals increased with the identification of its
      receptor, G-protein coupled receptor 14, and its localization in humans. UII and
      its receptor have a wide distribution, including brain and spinal cord as well as
      heart, kidney and liver, implying that UII has important physiological actions.
      Recent studies suggest that UII may play an important role in the central nervous
      system. In conscious sheep, intracerebroventricular administration of UII induced
      large, prolonged increases in plasma epinephrine, adrenocorticotropic hormone,
      cardiac output and arterial pressure. Potent chronotropic and inotropic actions
      accompanied this, as well as peripheral vasodilatation. Administered
      intravenously, UII is an extremely potent vasoconstrictor in anesthetized
      monkeys, but reduces pressure in conscious and anesthetized rats, and causes a
      transient increase in conscious sheep, however vasomotor responses vary depending
      on species and vessel type. UII is elevated in conditions such as essential
      hypertension and heart failure suggesting a role in pathology. The results of
      studies with UII to date, together with its possible role in disease, emphasize
      the importance of examining the central and peripheral roles of UII in more
      detail.

PMID- 15476944
TI  - Cellular distribution of immunoreactive urotensin-II in human tissues with
      evidence of increased expression in atherosclerosis and a greater constrictor
      response of small compared to large coronary arteries.
AB  - We detected urotensin-II-like immunoreactivity in the endothelium of normal human
      blood vessels from heart, kidney, placenta, adrenal, thyroid and umbilical cord.
      Immunoreactivity was also detected in endocardial endothelial and kidney
      epithelial cells. In atherosclerotic coronary artery, immunoreactivity localized
      to regions of macrophage infiltration. Urotensin-II constricted human
      atherosclerotic epicardial coronary arteries with pD2=10.58 +/- 0.46 (mean +/-
      S.E.M.) and Emax=11.4 +/- 4.2% KCl and small coronary arteries with pD2=9.25 +/-
      0.38 and Emax=77 +/- 16% KCl. Small coronary arteries clearly exhibited a greater
      maximum response to urotensin-II than epicardial vessels. This enhanced
      responsiveness may be of importance in heart failure, where circulating
      concentrations of U-II are increased, or in atherosclerosis where focally up
      regulated urotensin-II production may act down stream to produce significant
      vasospasm, compromising blood flow to the myocardium. We conclude that urotensin
      II is a locally released vasoactive mediator that may be an important regulator
      of blood flow particularly to the myocardium and may have a specific role in
      human atherosclerosis.

PMID- 15476945
TI  - Role of urotensin II in peripheral tissue as an autocrine/paracrine growth
      factor.
AB  - Urotensin II (UII), originally isolated from goby urophysis, has been shown to be
      an endogenous ligand for an orphan G-protein-coupled receptor, GPR14. Recent
      development of PCR quantitative method revealed that UII and UT receptor (GPR14)
      were expressed in a broad range of tissues and organs, including cardiovascular
      and renal system, and assumed to function as an autocrine/paracrine factor. UII
      is a potent vasoconstrictor peptide, whose potency is greater than any other
      vasoconstrictors thus far known. However, its physiological roles have been found
      to extend far beyond the regulation of vascular tone. In this review, we focused
      on the mitogenic action of UII and discuss its underlying cellular mechanisms and
      potential physiological/pathophysiological role in various human diseases.

PMID- 15476946
TI  - Cardiovascular role of urotensin II: effect of chronic infusion in the rat.
AB  - Urotensin II (UII) is a potent vaso-active peptide thought to have multiple roles
      in the regulation of cardiovascular physiology and pathophysiology. The actions
      of UII are complex and difficult to interpret given its systemic hemodynamic
      effects and variable action on different vascular beds and isolated vessels.
      Direct effects of UII on the myocardium, include myocyte hypertrophy,
      extracellular matrix deposition and contractility. These observations, together
      with elevated plasma levels found in disease, are common traits reported in other
      pathophysiologically implicated neurohormonal systems. In this review, we include
      original data obtained from chronic infusion of UII in rats. We report a
      reduction in first derivative of left ventricular pressure (+dP/dt), as well as
      an increase in the ratio of left ventricular collagen I:III, that may contribute
      to the reduced myocardial contractility observed in these animals.

PMID- 15476947
TI  - Urotensin II and cardiovascular diseases.
AB  - Urotensin II (UII) has been found to be a potent vasoactive peptide in humans and
      in a number of relevant animal models of cardiovascular disease such as the
      mouse, rat and other non-human primates. This peptide with structural homology to
      somatostatin was first isolated from the urophysis of fish and was recently found
      to bind to an orphan receptor in mouse and human. Initially found to have potent
      vasoconstrictive activities in a variety of vessels from diverse species, it has
      also been shown to exert vasodilatation in certain vessels in the rat and human
      by various endothelium-dependent mechanisms. The various vasoactive properties of
      UII suggest that the peptide may have a physiological role in maintaining
      vascular tone and therefore may have a role in the pathophysiology of a number of
      human diseases such as heart failure. Moreover, UII has also been implicated as a
      mitogen of vascular smooth muscle cells suggesting a deleterious role in
      atherosclerosis and coronary artery disease. In addition, there is evidence to
      demonstrate that UII has multiple metabolic effects on cholesterol metabolism,
      glycemic control and hypertension and therefore may be implicated in the
      development of insulin resistance and the metabolic syndrome.

PMID- 15476948
TI  - Urotensin II in the cardiovascular system.
AB  - Urotensin II is a peptide present, together with its receptor, in the central
      nervous system and many peripheral tissues (including heart, blood vessels,
      kidneys and endocrine organs) of many species. The bioactive, mature form
      contains a cyclic heptapeptide perfectly preserved across species spanning 550
      million years of evolution Its biological activity has been explored in cultured
      cells, in isolated vessels from several species, in the isolated perfused heart
      and in intact animals and man. Initial demonstration of potent vasoconstriction
      and cardiac depression by the human isoform in non-human primates has been
      followed by a series of reports indicating potent but highly variable and
      generally modest vascular responses dependent on species and vascular region. In
      man short term cardiovascular responses to administered urotensin II are small or
      absent. The place of urotensin II in the chronic trophic responses to cardiac and
      vascular injury and its possible roles as a neurotransmitter and/or regulator of
      renal and endocrine function remain largely unexplored.

PMID- 15476949
TI  - Genetic variations at urotensin II and urotensin II receptor genes and risk of
      type 2 diabetes mellitus in Japanese.
AB  - Urotensin II is among the most potent vasoactive hormones known and the urotensin
      II (UTS2) gene is localized to 1p36-p32, one of the regions reported to show
      possible linkage with type 2 diabetes in Japanese. When we surveyed genetic
      polymorphisms in the UTS2 and urotensin II receptor (GPR14) gene, we identified
      two SNPs with amino acid substitutions (designated T21M and S89N and an SNP in
      the promotor region (-605G>A) of the UTS2 gene, and two SNPs in the non-coding
      region of the GPR14 gene. We then studied these three SNPs in the UTS2 gene and
      two SNPs in the GPR14 gene in 152 Japanese subjects with type 2 diabetes mellitus
      and two control Japanese populations. The allele frequency of 89N was
      significantly higher in type 2 diabetic patients than in both elderly normal
      subjects (P = 0.0018) and subjects with normal glucose tolerance (P = 0.0011),
      whereas the allele frequency of T21M and -605G>A in the UTS2 gene and those of
      two SNPs in the GPR14 gene were essentially identical in these three groups.
      Furthermore, in the subjects with normal glucose tolerance, 89N was associated
      with significantly higher insulin levels on oral glucose tolerance test,
      suggesting reduced insulin sensitivity in subjects with 89N. These results
      strongly suggest that subjects with S89N in the UTS2 gene are more insulin
      resistant and thus more susceptible to type 2 diabetes mellitus development.

PMID- 15476950
TI  - Elevated plasma levels of immunoreactive urotensin II and its increased urinary
      excretion in patients with Type 2 diabetes mellitus: association with progress of
      diabetic nephropathy.
AB  - Urotensin II (UII) is the most potent vasoconstrictor peptide ever identified. In
      order to clarify the pathophysiological role of UII in diabetes mellitus, we
      examined plasma immunoreactive UII levels and urinary excretion of immunoreactive
      UII in 10 control subjects and 48 patients with Type 2 diabetes mellitus. The
      patients were divided into three groups according to the renal function: Group I
      with Ccr > or = 70 ml/min, group II with 30 < or = Ccr <70 ml/min and group III
      with Ccr <30 ml/min. Plasma immunoreactive UII levels were elevated in the three
      diabetic groups compared with normal controls (P <0.05). Group III patients had
      significantly higher plasma immunoreactive UII levels (15.9 +/- 2.2 fmol/ml, mean
      +/- S.E.M., n=6) by approximately 1.6-fold than did group I (10.9 +/- 0.9
      fmol/ml, n=17) and group II (10.8 +/- 0.8 fmol/ml, n=25) (P <0.05). Urinary
      excretion of immunoreactive UII was significantly increased in group III patients
      (52.4 +/- 14.8 pmol/day) by more than 1.8-fold compared with control subjects,
      groups I and II (P <0.005). Fractional excretion of immunoreactive UII
      significantly increased as renal function decreased. Presence of diabetic
      retinopathy or neuropathy had negligible effects on plasma immunoreactive UII
      levels and urinary immunoreactive UII excretion. Reverse phase HPLC analyses
      showed three immunoreactive peaks in normal plasma extracts and multiple
      immunoreactive peaks in normal urine extracts. Thus, Type 2 diabetes mellitus
      itself is a factor to elevate plasma immunoreactive UII levels, and accompanying
      renal failure is another independent factor for the increased plasma
      immunoreactive UII levels in Type 2 diabetic patients. Increased urinary
      immunoreactive UII excretion in Type 2 diabetic patients with advanced diabetic
      nephropathy may be due not only to the elevated plasma immunoreactive UII levels
      but also to increased UII production and/or decreased UII degradation in the
      diseased kidney.

PMID- 15476951
TI  - Urotensin II-related peptide, the endogenous ligand for the urotensin II receptor
      in the rat brain.
AB  - Urotensin II (UII) is a piscine neuropeptide originally isolated from the teleost
      urophysis. The existence of UII in mammals has been demonstrated by cloning of
      the mammalian orthologs of UII precursor protein genes. While rat and mouse
      orthologs have been reported, only the tentative structures of UII peptides of
      these animals have been demonstrated, since prepro-UII proteins lack the typical
      processing sites in the amino-terminal region of the mature peptides. A novel
      peptide, UII-related peptide (URP), was discovered by monitoring UII
      immunoreactivity in the rat brain, and its amino acid sequence was determined to
      be ACFWKYCV. cDNAs encoding rat, mouse, and human precursor proteins for URP were
      cloned and showed that the sequences of mouse and human URP peptides are
      identical to that for rat URP. URP was found to bind and activate the human or
      rat urotensin II receptors [GPR14, UT receptor (UTR)] and showed a hypotensive
      effect when administrated to anesthetized rats. The prepro-URP gene is expressed
      in several rat tissues, although with lower levels than the prepro-UII gene and,
      in the human, is expressed comparably to prepro-UII in several tissues except the
      spinal cord. These results suggest that URP is the endogenous and functional
      ligand for urotensin II receptor in the rat and mouse, and possibly in the human.

PMID- 15476952
TI  - Structure-activity relationships and structural conformation of a novel urotensin
      II-related peptide.
AB  - Urotensin II (UII) has been described as the most potent vasoconstrictor peptide
      and recognized as the endogenous ligand of the orphan G protein-coupled receptor
      GPR14. Recently, a UII-related peptide (URP) has been isolated from the rat brain
      and its sequence has been established as H-Ala-Cys-Phe-Trp-Lys-Tyr-Cys-Val-OH. In
      order to study the structure-function relationships of URP, we have synthesized a
      series of URP analogs and measured their binding affinity on hGPR14-transfected
      cells and their contractile activity in a rat aortic ring bioassay. Alanine
      substitution of each residue of URP significantly reduced the binding affinity
      and the contractile activity of the peptides, except for the Ala8-substituted
      analog that retained biological activity. Most importantly, D-scan of URP
      revealed that [D-Trp4]URP abrogated and [D-Tyr6]URP partially suppressed the UII
      evoked contractile response. [Orn5]URP, which had very low agonistic efficacy,
      was the most potent antagonist in this series. The solution structure of URP has
      been determined by 1H NMR spectroscopy and molecular dynamics. URP exhibited a
      single conformation characterized by an inverse gamma-turn comprising residues
      Trp-Lys-Tyr which plays a crucial role in the biological activity of URP. These
      pharmacological and structural data should prove useful for the rational design
      of non-peptide ligands as potential GPR14 agonists and antagonists.

PMID- 15476953
TI  - The laboratory assessment of enamel erosion: a review.
AB  - OBJECTIVES: To review the various methods and techniques available to assess
      enamel erosion in vitro. DATA: Peer reviewed scientific articles. SOURCES:
      Medline and Web of Science searches and manual searching. STUDY SELECTION:
      Laboratory based assessments only included. CONCLUSIONS: A number of macroscopic
      and microscopic techniques have been used to assess enamel erosion in vitro and
      in situ. This review examines techniques which are either well established or
      comparatively novel techniques that are being explored for their potential.

PMID- 15476954
TI  - Factors affecting the accuracy of elastometric impression materials.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effects of (1) various
      impression materials, (2) different storage times and (3) the proportion of
      inorganic filler on the accuracy and stability of elastometric impression
      materials. METHODS: The impression materials studied included three alginate
      impression materials (Algiace Z, CAVEX and Jeltrate), five commercial silicone
      impression materials (Aquasil, Exaflex regular type, Express, Coltex fine and
      Rapid liner) and two experimental silicone impression materials designed for this
      study (KE106A and KE106B). Impressions were made of 10 metal dies that mimicked
      prepared crowns. After an impression was taken, dental stone was immediately
      poured into the alginate impressions, while the silicone impressions was poured
      30 min later and waited for 1 h for setting. The second and third stone dies were
      made 1 and 24 h later, respectively. The diameters of the occlusal surfaces of
      the metal dies and stone casts were determined using photographs of the surfaces
      taken with a Kodak DC 290 digital camera. The pictures were then measured using a
      photomicrograph digitized integration system to calculate any discrepancy.
      Because each impression was used to make three rounds of stone dies, two-factor
      mixed factorial ANOVA was used to evaluate the effect of materials and storage
      time on the accuracy of the stone casts. The simple effects analysis, combined
      with multiple comparisons considering the per family type I error rate, was
      performed following confirmation that an interaction between the two factors was
      significant. RESULTS: The results showed that: (1) there was a significant
      interaction effect between materials and storage times on the accuracy of the
      impressions. (2) Two addition type silicone materials, Aquasil and Exaflex, had
      the greatest accuracy and stability. (3) The experimental material KE106A had the
      least accuracy in the first and second rounds and the alginate impression
      material CAVEX had the least accuracy in the third round. (4) The stabilities of
      CAVEX and Jeltrate were the least consistent of the 10 materials and decreased
      significantly with storage time. (5) When the experimental material had a low
      proportion of filler (KE106A), there was a significantly greater dimensional
      discrepancy compared to the same material with a higher proportion of filler
      (KE106B). CONCLUSIONS: The accuracies varied among the 10 impression materials
      over three rounds. Of all the materials, the addition type silicone materials,
      Aquasil and Exaflex, had relatively greater accuracy and stability. The
      discrepancy of the alginate impression materials increased with storage time. The
      large loading of filler showed less discrepancy.

PMID- 15476955
TI  - Single-bottle adhesives behave as permeable membranes after polymerization. I. In
      vivo evidence.
AB  - OBJECTIVES: This study tested the hypothesis that single-bottle total-etch
      adhesives are effective in reducing dentine permeability under in vivo
      conditions. METHODS: Crown preparations on vital human teeth were performed under
      local analgesia as part of the treatment plan for prosthetic rehabilitation. Four
      single-bottle adhesives (Single Bond, 3M ESPE; Excite DSC, Ivoclar Vivadent;
      Prime and Bond NT Dual-Cure, Dentsply DeTrey and One-Step, Bisco Inc.) were
      applied to the cut dentine after acid-etching. Polyvinyl siloxane impressions
      were taken, using an ultra-low viscosity impression material, of the smear layer
      covered dentine before applying the adhesives to deep vital dentine, and after
      adhesive placement. Additional impressions were taken of the adhesive-sealed
      dentine following the removal of the provisional prostheses after a 7-10 day
      period. Epoxy resin replicas of the crown preparations were examined with
      scanning electron microscopy to evaluate the extent of dentinal fluid
      transudation during pre-bonded, immediately bonded and post-bonded periods.
      RESULTS: Dentinal fluid transudation from localised areas that were close to the
      dental pulp was universally observed from all epoxy resin replicas, irrespective
      of the adhesive employed. The transudation of dentinal fluid from the control
      smear layer-covered dentine of each crown preparation was comparatively mild when
      compared to the extent that was observed after total-etching and application of
      the single-bottle adhesive. Dentinal fluid droplets were specifically located
      over the surface of the adhesive layer. Continuous transudation of dentinal fluid
      occurred even after the removal of the provisional prostheses, and was
      considerably more profuse in subjects who opted for the fitting of the permanent
      prostheses without the use of a local anaesthetic solution. CONCLUSION: Single
      bottle adhesives, because of their lack of a comparatively more hydrophobic
      bonding resin layer, behave as permeable membranes after polymerisation. They
      permit the continuous transudation of dentinal fluid and do not provide a
      hermetic seal in vital deep dentine. Although the relatively slow rate of
      diffusion of dentinal fluid is unlikely to result in post-operative cold
      sensitivity, it may interfere with the optimal polymerisation of dual-cured or
      auto-cured composites or resin cements in both direct and indirect restorations.

PMID- 15476956
TI  - Automated quantification of dental plaque accumulation using digital imaging.
AB  - OBJECTIVES: Most dental plaque indices have a subjective component due to
      investigator interpretation. To assess the accumulation of plaque on teeth, a
      fully automated method was developed based on digital imaging of methylene blue
      (1% (w)/(v)) disclosed plaque. METHODS: Intra-oral colour images of disclosed
      plaque from 25 individuals were coded into hue, saturation and intensity colour
      space. Unequivocal areas of clean teeth, plaque and clean gingiva were sampled to
      determine the typical values of hue, saturation and intensity of light. RESULTS:
      Discriminant analysis showed that the success rate for classification of the
      pixels as plaque and non-plaque was 87.3% based on saturation and intensity, and
      98.7% for a classifier based on hue and intensity. Fisher's function coefficients
      were used to create classification boundaries in the colour space which would
      allow to automatically classify new images. CONCLUSIONS: This method has
      potential for automated and quantitative measurement screening of dental plaque
      that may be used to assess the efficacy of oral hygiene products and procedures.

PMID- 15476957
TI  - Translucent fiber post cementation using a light-curing adhesive/composite
      system: SEM analysis and pull-out test.
AB  - OBJECTIVES: The performance of both light-curing and dual-cured adhesive/luting
      systems (as control), when used in combination with translucent fibre posts, was
      evaluated by means of pull-out test and scanning electron microscopy (SEM )
      observation. METHODS: Forty root canal treated teeth were randomly divided into
      two groups of 20 specimens each. Group 1 light-curing system: Excite and Tetric
      Flow; Group 2 dual cured system: All Bond 2+RelyX ARC. Translucent, double taper
      fibre posts were used (2.1/1.4mm diameter). The teeth were stored in NaCl 0.9%
      solution at 37 degrees C. A week later, the pull-out test was carried out on all
      specimens. Ten tested specimens for each group and their corresponding posts were
      processed for SEM observation. Statistical analysis was performed applying one
      way analysis of variance (ANOVA) followed by T-test as post-hoc comparison at a
      significance level set at p<0.05. RESULTS: There is no statistically significant
      difference (p>0.05) between the light-curing system group (275.2+/-58.9N) and the
      dual cured one (301.4+/-40.1N). SEM observations confirm a good bond between the
      dentine and the post whatever the curing method employed. CONCLUSIONS: Dual
      curing of the All Bond 2+RelyX ARC system seems to be the most appropriate method
      since it allows to cure even those areas which would not be otherwise reached by
      light. On the other hand, in apical areas, the incomplete curing of the
      Excite+Tetric Flow system could improve the post adaptation and allow the
      achievement of both an improved apical seal and a more even distribution of the
      stress along the canal walls.

PMID- 15476958
TI  - Increased fluoride uptake and acid resistance by CO2 laser-irradiation through
      topically applied fluoride on human enamel in vitro.
AB  - OBJECTIVES: The aim of the current in vitro study was to evaluate the effect of
      CO(2)-laser treatment immediately after applying amine fluoride solution on
      enamel. It was hypothesized that such a treatment would increase enamel fluoride
      uptake, and reduce dissolution rate and thermal surface alterations. METHODS:
      Fluoride uptake was determined in 40 human enamel sections randomly assigned to
      four groups (n=10), which were either left untreated (1), exposed to a 1% amine
      fluoride solution for 15s without irradiation (2), irradiated for 15s with a
      continuous-wave carbon dioxide laser (3), or laser-treated for 15s through the
      amine fluoride solution applied immediately beforehand (4). Fluoride uptake was
      determined with an ion selective electrode after acid dissolution of the
      specimens (surface and subsurface layers). For the determination of acid
      resistance, another 40 enamel sections were treated according to the above
      protocol. Acid resistance was determined in surface and subsurface layers by
      measuring eluted calcium upon 3% lactic acid exposure with atomic absorption
      spectrometry. Enamel surface alterations after laser irradiation were monitored
      using scanning electron microscopy. RESULTS: Laser irradiation through the
      fluoride solution led to significantly higher fluoride contents in the surface
      enamel layer compared to fluoride treatment alone or laser treatment alone
      (p=0.002). Laser treatment with or without fluoride resulted in an increased acid
      resistance of enamel specimens. Fewer surface alterations were observed upon SEM
      examination of specimens irradiated through the amine fluoride solution compared
      to counterparts treated with laser only. CONCLUSIONS: CO(2) laser light
      application through an amine fluoride solution may be useful and effective in the
      prevention of caries.

PMID- 15476959
TI  - Thermal changes and cure depths associated with a high intensity light activation
      unit.
AB  - OBJECTIVES: The objectives of this study were to evaluate the thermal emission
      and curing characteristics of a high intensity halogen light (Astralis 10-Ivoclar
      Vivadent, Schaan. Leichtenstein) alone and on curing a conventional and a fast
      curing micro-hybrid composite. METHODS: A bead thermistor was placed in the base
      of a standard model cavity. The cavity was irradiated using the light unit whilst
      empty, and when filled with either composite. Temperature rises were recorded
      using the light in four different output modes. Further samples were prepared to
      assess depth of cure via a digital penetrometer, light transmission using a
      computer-based radiometer, and microhardness with a Wallace hardness tester.
      RESULTS: Mean peak temperature rises recorded during polymerisation of the
      composites ranged from 6.9 degrees C for the product InTen-S cured with the
      Adhesive programme (Adh) to 11.0 degrees C for the product Tetric Ceram HB cured
      with the High Power (HI P) programme. A significantly greater depth of cure was
      obtained for InTen-S in line with the greater light transmission obtained for
      this material. DISCUSSION: The very high thermal emission characteristics
      reported in a recently published investigation for this light unit were not
      confirmed. CONCLUSIONS: As the extent of thermal trauma that can be tolerated by
      the dental pulp is unknown consideration should be given to the choice of light
      activation unit and curing programme when polymerising light activated resin
      based restorations in deep cavities close to the pulp.

PMID- 15476960
TI  - The use of a 3D laser scanner using superimpositional software to assess the
      accuracy of impression techniques.
AB  - OBJECTIVE: Several studies have made comparisons in the dimensional accuracy of
      different elastomeric impression materials. Most have used two-dimensional
      measuring devices, which neglect to account for the dimensional changes that
      exist along a three-dimensional surface. PURPOSE: The aim of this study was to
      compare the dimensional accuracy of an impression technique using a polyether
      material (Impregum) and a vinyl poly siloxane material (President) using a laser
      scanner with three-dimensional superimpositional software. MATERIALS AND METHODS:
      Twenty impressions, 10 with a polyether and 10 with addition silicone, of a stone
      master model that resembled a dental arch containing three acrylic posterior
      teeth were cast in orthodontic stone. One plastic tooth was prepared for a metal
      crown. The master model and the casts were digitised with the non-contacting
      laser scanner to produce a 3D image. 3D surface viewer software superimposed the
      master model to the stone replica and the difference between the images analysed.
      RESULTS: The mean difference between the model and the stone replica made from
      Impregum was 0.072mm (SD 0.006) and that for the silicone 0.097mm (SD 0.005) and
      this difference was statistically significantly, p=0.001. CONCLUSIONS: Both
      impression materials provided an accurate replica of the prepared teeth
      supporting the view that these materials are highly accurate.

PMID- 15476961
TI  - Finite element contact stress analysis of the RPD abutment tooth and periodontal
      ligament.
AB  - OBJECTIVES: The purpose of this study was to determine the influence of the
      occlusal rest position in removable partial dentures on the displacement of the
      abutment tooth and the stress distribution in the periodontal ligament (PL).
      METHODS: We constructed three-dimensional finite element models of the mandibular
      first and second premolars. A layer of the PL and a mesial or distal occlusal
      rest were produced on the second premolar as an abutment. A zero displacement was
      prescribed on the outer surface of the PL and the first premolar. In each
      simulation, the rest was moved 0.05 mm vertically to the apical direction, with
      or without restriction of horizontal movements. We simulated the contact
      phenomena on the abutment surfaces, and calculated the movements of the abutment
      and stress distributions in the PL. RESULTS: We observed a maximum distal
      displacement of 42 microm at the buccal cusp of the abutment and a principal
      compressive stress of 0.35 MPa in the PL when the abutment was vertically loaded
      by a distal rest that was allowed to move horizontally. However, the
      displacements and stresses were relatively small, and were all within the
      physiological limitations of the tissues. The restriction of the horizontal
      movement of the rests was effective in reducing the horizontal displacements of
      the abutment, regardless of the rest position. CONCLUSIONS: The single vertical
      load exerted from either the mesial or distal rest on the abutment was unlikely
      to cause any mechanical damage to its supporting tissues.

PMID- 15476962
TI  - In vitro growth, acidogenicity and cariogenicity of predominant human root caries
      flora.
AB  - Streptococcus mutans (Sm), Lactobacillus acidophilus (La) and Actinomyces
      israelii (Ai) have been associated with root surface caries, which is an
      increasing problem in elderly Chinese. The aim of this study therefore, was to
      evaluate in vitro, the growth, acidogenicity and cariogenicity of these
      organisms, both in mono- and co-cultures using an in vitro model. Forty-eight
      root specimens were prepared using intact extracted human molars. Fresh, wild
      type bacteria obtained from root caries lesions were assembled into seven
      experimental groups as either mono- or co-cultures and incubated with the root
      specimens. Appropriate controls were included. Growth curve of each experimental
      group was monitored for 24h, aerobically, at 37 degrees C using a microplate
      reader. The pH of the medium was recorded after 24-h incubation using a pH meter.
      Mean depths of artificial root lesions produced in each cultural group were
      measured using polarized light microscopy in specimens cut into thin sections
      (100+/-20 microm). Compared with mono-cultures, synergistic growth was observed
      in co-cultures of 'La+Sm', 'Ai+La' and 'Ai+La+Sm'. Mean lesion depth produced in
      La group was significantly shallower than other mono- or co-culture groups
      (p<0.01). The pH values of all culture media were similar after 24-h incubation.
      The current data elucidate the complex interactions of three predominant
      bacterial species considered prime agents of human root surface caries.

PMID- 15476963
TI  - The 19th International WAAVP Conference in New Orleans.

PMID- 15476964
TI  - History of the World Association for the Advancement of Veterinary Parasitology
      (WAAVP).
AB  - Forty years ago the first meeting of the World Association for the Advancement of
      Veterinary Parasitiology (WAAVP) was held in Hannover, Germany. We now have a
      thriving, internationally recognized organization; the meetings attract hundreds
      of scientists, attendance is increasing with almost every meeting. It is a useful
      time to review our beginnings, our development and our future. Our history has
      been one of innovation and activity and contributed to by its members in
      important areas of veterinary parasitology.

PMID- 15476965
TI  - The livestock revolution--a global veterinary mission.
AB  - Increasing population, urbanisation and disposable incomes in developing
      countries are fuelling a strong growth in demand for animal food products, which
      in turn will have a strong impact on the location and organisation of global
      livestock production. Changes in the latter will in turn strongly impinge on
      animal and human health, the livelihoods of the poor and the environment. The
      consequences of these trends, termed the 'livestock revolution', are expected to
      dramatically change the face of animal agriculture in coming decades, including a
      major increase in the developing countries' share in world livestock production
      and consumption; a gradual substitution of cereals and other basic foods with
      meat and milk in the developing countries' diets; a change from multiple
      production objectives to more specialised intensive meat, milk and egg production
      within an integrated global food and feed market; a shift to more industrial
      production and processing; rising use of cereal-based animal feeds; and greater
      stress on fragile extensive pastoral areas and more pressure on land in areas
      with very high population densities and close to urban centres. Henning
      Steinfeld, an agricultural economist from the Food and Agriculture Organization
      of the United Nations, reviews here trends associated with the 'Livestock
      Revolution' and predicted implications for animal health. The presentation was
      given in a plenary session at the 19th International Conference of the World
      Association for the Advancement of Veterinary Parasitology (WAAVP) held in New
      Orleans, Louisiana, USA during 10-14 August 2003.

PMID- 15476966
TI  - Factors that influence the prevalence of acaricide resistance and tick-borne
      diseases.
AB  - This manuscript provides a summary of the results presented at a symposium
      organized to accumulate information on factors that influence the prevalence of
      acaricide resistance and tick-borne diseases. This symposium was part of the 19th
      International Conference of the World Association for the Advancement of
      Veterinary Parasitology (WAAVP), held in New Orleans, LA, USA, during August 10
      14, 2003. Populations of southern cattle ticks, Boophilus microplus, from Mexico
      have developed resistance to many classes of acaricide including chlorinated
      hydrocarbons (DDT), pyrethroids, organophosphates, and formamidines (amitraz).
      Target site mutations are the most common resistance mechanism observed, but
      there are examples of metabolic mechanisms. In many pyrethroid resistant strains,
      a single target site mutation on the Na(+) channel confers very high resistance
      (resistance ratios: >1000x) to both DDT and all pyrethroid acaricides.
      Acetylcholine esterase affinity for OPs is changed in resistant tick populations.
      A second mechanism of OP resistance is linked to cytochrome P450 monooxygenase
      activity. A PCR-based assay to detect a specific sodium channel gene mutation
      that is associated with resistance to permethrin has been developed. This assay
      can be performed on individual ticks at any life stage with results available in
      a few hours. A number of Mexican strains of B. microplus with varying profiles of
      pesticide resistance have been genotyped using this test. Additionally, a
      specific metabolic esterase with permethrin-hydrolyzing activity, CzEst9, has
      been purified and its gene coding region cloned. This esterase has been
      associated with high resistance to permethrin in one Mexican tick population.
      Work is continuing to clone specific acetylcholinesterase (AChE) and
      carboxylesterase genes that appear to be involved in resistance to
      organophosphates. Our ultimate goal is the design of a battery of DNA- or ELISA
      based assays capable of rapidly genotyping individual ticks to obtain a
      comprehensive profile of their susceptibility to various pesticides. More
      outbreaks of clinical bovine babesisois and anaplasmosis have been associated
      with the presence of synthetic pyrethroid (SP) resistance when compared to OP and
      amidine resistance. This may be the result of differences in the temporal and
      geographic patterns of resistance development to the different acaricides. If
      acaricide resistance develops slowly, herd immunity may not be affected. The use
      of pesticides for the control of pests of cattle other than ticks can affect the
      incidence of tick resistance and tick-borne diseases. Simple analytical models of
      tick- and tsetse-borne diseases suggest that reducing the abundance of ticks, by
      treating cattle with pyrethroids for example, can have a variety of effects on
      tick-borne diseases. In the worst-case scenario, the models suggest that treating
      cattle might not only have no impact on trypanosomosis but could increase the
      incidence of tick-borne disease. In the best-case, treatment could reduce the
      incidence of both trypanosomosis and tick-borne diseases Surveys of beef and
      dairy properties in Queensland for which tick resistance to amitraz was known
      were intended to provide a clear understanding of the economic and management
      consequences resistance had on their properties. Farmers continued to use amitraz
      as the major acaricide for tick control after the diagnosis of resistance,
      although it was supplemented with moxidectin (dairy farms) or fluazuron,
      macrocyclic lactones or cypermethrin/chlorfenvinphos.

PMID- 15476967
TI  - A xylose-inducible expression system for Lactococcus lactis.
AB  - A new controlled production system to target heterologous proteins to cytoplasm
      or extracellular medium is described for Lactococcus lactis NCDO2118. It is based
      on the use of a xylose-inducible lactococcal promoter, P(xylT). The capacities of
      this system to produce cytoplasmic and secreted proteins were tested using the
      Staphylococcus aureus nuclease gene (nuc) fused or not to the lactococcal Usp45
      signal peptide. Xylose-inducible nuc expression is tightly controlled and
      resulted in high-level and long-term protein production, and correct targeting
      either to the cytoplasm or to the extracellular medium. Furthermore, this
      expression system is versatile and can be switched on or off easily by adding
      either xylose or glucose, respectively. These results confirm the potential of
      this expression system as an alternative and useful tool for the production of
      proteins of interest in L. lactis.

PMID- 15476968
TI  - Identification of the ornithine decarboxylase gene in the putrescine-producer
      Oenococcus oeni BIFI-83.
AB  - We report here the identification of an ornithine decarboxylase (ODC) gene in the
      putrescine-producer Oenococcus oeni BIFI-83 strain. The gene contains a 2,235
      nucleotide open reading frame encoding a 745-amino acid residues protein with a
      deduced molecular mass of 81 kDa. The primary structure of the ODC deduced from
      the nucleotide sequence has a consensus sequence containing the pyridoxal-5
      phosphate (PLP) binding domain, and the critical amino acids residues involved in
      enzymatic activity are also conserved. As determined by BLAST analysis, the
      deduced amino acid sequence of the odc gene shares a 67% identity with the ODC
      protein from Lactobacillus 30a. The odc gene appears to be rarely present in the
      genome of O. oeni, since in a screening for the presence of this gene in 42
      oenococcal strains none of the strains possessed an odc gene copy.

PMID- 15476969
TI  - S-Nitrosoglutathione cytotoxicity to Mycobacterium smegmatis and its use to
      isolate stationary phase survival mutants.
AB  - We report that stationary phase Mycobacterium smegmatis is more sensitive than
      exponential phase cells to the nitric oxide donor S-Nitrosoglutathione (GSNO).
      This finding was used to select for both spontaneous and transposon mutants of M.
      smegmatis with increased resistance to GSNO in stationary phase. Some of these
      mutants were also defective in stationary phase survival, demonstrating a link
      between sensitivity to GSNO and stationary phase survival. Transduction of the
      disrupted region from seven selected mutants indicated that the transposon
      insertion was linked to the GSNO-resistance and stationary phase survival
      phenotypes. For five mutants, the disrupted genes were identified. Three were
      homologous to genes with possible roles in nutrient scavenging, including: (i) a
      putative amino acid efflux pump, (ii) a putative thioesterase and (iii) an enoyl
      CoA-hydratase. One mutant was disrupted in the atpD gene, encoding the beta chain
      of F1 F0 ATP synthase. We independently isolated a stationary phase survival
      mutant disrupted in the atpA gene (encoding the alpha chain) of the F1 F0 ATP
      synthase of the same operon, suggesting an important role for efficient ATP
      synthesis in stationary phase survival.

PMID- 15476970
TI  - Inhibition of aerobic respiration and dissimilatory perchlorate reduction using
      cyanide.
AB  - The effect of low concentrations of cyanide on dissimilatory perchlorate and
      chlorate reduction and aerobic respiration was examined using pure cultures of
      Azospira sp. KJ. Cyanide at a concentration of 38 microM inhibited cell growth on
      perchlorate, chlorate and molecular oxygen, but it did not inhibit the activity
      of chlorite dismutase. When oxygen accumulation was prevented by adding an oxygen
      scavenger (Oxyrase or L-cysteine), however, cells completely reduced perchlorate
      in the presence of cyanide. It was concluded that the inhibition of dissimilative
      perchlorate reduction by cyanide at this concentration was a consequence of
      oxygen accumulation, not inhibition of the enzymes used for perchlorate
      reduction. This finding on the effect of cyanide on respiratory enzymes provides
      a new method to control and study respiratory enzymes used for perchlorate
      reduction.

PMID- 15476971
TI  - Intriguing diversity of Bacillus anthracis in eastern Poland--the molecular
      echoes of the past outbreaks.
AB  - The multiple locus VNTRs analysis (MLVA) revealed the presence of five genotypes
      in a group of 10 Bacillus anthracis isolates from epidemiologically unrelated
      cases of bovine-anthrax in eastern Poland. Eight tested isolates possessed the
      pagA and capB genes indicating the presence of both virulence plasmids, while two
      isolates revealed only pagA and lacked pXO2. The MLVA and DNA sequence analysis
      indicated that seven tested isolates represent four novel genotypes. Five tested
      strains revealed a unique 144 bp vrrB2 variant as well as 220 bp variant of
      vrrB1, implying the relatedness to the lineage B2. Consequently, we propose
      establishing of novel B2 strains sub-lineage. Multiple anthrax outbreaks, which
      took place in Poland several decades ago were proposed as a cause of intriguing
      diversity of B. anthracis observed in this study.

PMID- 15476972
TI  - Identification of an antibacterial compound, benzylideneacetone, from Xenorhabdus
      nematophila against major plant-pathogenic bacteria.
AB  - An entomopathogenic bacterium, Xenorhabdus nematophila, is known to have potent
      antibiotic activities to maintain monoxenic condition in its insect host for
      effective pathogenesis and ultimately for optimal development of its nematode
      symbiont, Steinernema carpocapsae. In this study we assess its antibacterial
      activity against plant-pathogenic bacteria and identify its unknown antibiotics.
      The bacterial culture broth had significant antibacterial activity that increased
      with development of the bacteria and reached its maximum at the stationary growth
      phase. The antibiotic activities were significant against five plant-pathogenic
      bacterial strains: Agrobacterium vitis, Pectobacterium carotovorum subsp.
      atrosepticum, P. carotovorum subsp. carotovorum, Pseudomonas syringae pv. tabaci,
      and Ralstonia solanacearum. The antibacterial factors were extracted with butanol
      and fractionated using column chromatography with the eluents of different
      hydrophobic intensities. Two active antibacterial subfractions were purified, and
      the higher active fraction was further fractionated and identified as a single
      compound of benzylideneacetone (trans-4-phenyl-3-buten-2-one). With heat
      stability, the synthetic compound showed equivalent antibiotic activity and
      spectrum to the purified compound. This study reports a new antibiotic compound
      synthesized by X. nematophila, which is a monoterpenoid compound and active
      against some Gram-negative bacteria.

PMID- 15476973
TI  - Endemic occurrence of infections by multidrug-resistant Escherichia coli of four
      unique serotypes in the elderly population of Israel.
AB  - During a period of four years, multidrug-resistant Escherichia coli of particular
      serotypes have been isolated from 255 elderly (>65 years) patients from four
      hospitals in central Israel. 83% of the isolates belonged to one of four
      predominant serotypes (O153:H31, O101:H-, O2:H42, and O102:H6). All isolates were
      producers of extended spectrum beta-lactamases and resistant to ciprofloxacin. To
      our knowledge, the involved serotypes have hitherto not been reported as
      etiological agents of extraintestinal human infections (MEDLINE). Pulsed-field
      gel electrophoresis of isolates from one of the most frequent serotypes indicated
      a clonal relationship between them. Further investigation of these strains and
      analysis of their virulence factors may help to confine their spread.

PMID- 15476974
TI  - Occurrence of D-histidine residues in antimicrobial poly(arginyl-histidine),
      conferring resistance to enzymatic hydrolysis.
AB  - The antimicrobial peptide poly(arginyl-histidine) is secreted by the ergot fungus
      Verticillium kibiense. We previously showed that poly(arginyl-histidine) from the
      fungus inhibits the growth of certain microorganisms more effectively than that
      chemically synthesized from the L-form of arginine and histidine, implying some
      substantial differences between the fungal and synthetic peptides. To elucidate
      what causes such differences, we here investigated the structural features of the
      fungal peptides. The acid hydrolysates of the fungal peptide contained d
      histidine. When synthetic poly(L-arginyl-D-histidine) mimicking the fungal
      peptide was added to the culture of Salmonella typhimurium together with poly(L
      arginyl-L-histidine), poly(L-arginyl-D-histidine) was not easily degraded during
      the incubation compared with poly(L-arginyl-L-histidine). We concluded that the d
      form of histidine residues in the fungal peptide prolongs the life of the peptide
      leading to the enhancement of antimicrobial activity.

PMID- 15476975
TI  - Colony dimorphism associated with stress resistance in Oenococcus oeni VP01 cells
      during stationary growth phase.
AB  - The resistance to stresses as starvation, the presence of ethanol, sulfite and
      low pH, is a fundamental prerequisite for starter cultures used to induce
      malolactic fermentation in wine. In order to evaluate stress resistance of cells
      undergone starvation, cells viability in laboratory cultures of Oenococcus oeni
      VP01 strain was monitored during prolonged stationary growth phase. Once entered
      the stationary phase, strain VP01 showed 99% reduction of cell viability within 4
      days. The remaining cells population maintained viability over 70 days and, when
      plated on agar medium, generated small colonies. The occurrence of this
      phenomenon was associated to stress resistance, since 10-day-old cells resulted
      more resistant than 3-day-old cells to ethanol and low pH conditions. No genomic
      mutations were revealed by pulse-field gel electrophoresis (PFGE) analysis in
      aged cultures. Total protein analysis by bidimensional electrophoresis
      highlighted differential protein expression in cultures differentially aged. It
      was demonstrated that O. oeni starving cultures at the stationary phase are
      constituted by dynamic cell populations. These results offer interesting
      perspective for a better understanding of cells behavior when inoculated in wine.

PMID- 15476976
TI  - Rapid identification of probiotic Lactobacillus species by multiplex PCR using
      species-specific primers based on the region extending from 16S rRNA through 23S
      rRNA.
AB  - This study aimed to develop a novel multiplex polymerase chain reaction (PCR)
      primer set for the identification of seven probiotic Lactobacillus species such
      as Lactobacillus acidophilus, Lactobacillus delbrueckii, Lactobacillus casei,
      Lactobacillus gasseri, Lactobacillus plantarum, Lactobacillus reuteri and
      Lactobacillus rhamnosus. The primer set, comprising of seven specific and two
      conserved primers, was derived from the integrated sequences of 16S and 23S rRNA
      genes and their rRNA intergenic spacer region of each species. It was able to
      identify the seven target species with 93.6% accuracy, which exceeds that of the
      general biochemical methods. The phylogenetic analyses, using 16S rDNA sequences
      of the probiotic isolates, also provided further support that the results from
      the multiplex PCR assay were trustworthy. Taken together, we suggest that the
      multiplex primer set is an efficient tool for simple, rapid and reliable
      identification of seven Lactobacillus species.

PMID- 15476977
TI  - Heterologous complementation of the exopolysaccharide synthesis and carbon
      utilization phenotypes of Sinorhizobium meliloti Rm1021 polyhydroxyalkanoate
      synthesis mutants.
AB  - A reduced exopolysaccharide phenotype is associated with inability to synthesize
      polyhydroxyalkanaote (PHA) stores in Sinorhizobium meliloti strain Rm1021. Loss
      of function mutations in phbB and phbC result in non-mucoid colony morphology on
      Yeast Mannitol Agar, compared to the mucoid phenotype exhibited by the parental
      strain. This phenotype is attributed to reduction in succinoglycan synthesis. We
      have used complementation of this phenotype and the previously described D-3
      hydroxybutyrate/acetoacetate utilization phenotype to isolate a heterologous
      clone containing a Bradyrhizobium japonicum phbC gene. Sequence analysis
      confirmed that this clone contains one of the five predicted phbC genes in the B.
      japonicum genome. The described phenotypic complementation strategy should be
      useful for isolation of novel PHA synthesis genes of diverse origin.

PMID- 15476978
TI  - Cloning and functional analysis by gene disruption of a novel gene involved in
      indigo production and fluoranthene metabolism in Pseudomonas alcaligenes PA-10.
AB  - A novel indole dioxygenase (idoA) gene has been cloned from Pseudomonas
      alcaligenes PA-10, based on its ability to convert indole to indigo. The
      chromosomally encoded idoA gene exhibits no similarity to previously cloned
      naphthalene dioxygenases or to aromatic oxygenases from other species at the
      nucleotide level. Phylogenetic analysis indicates that the idoA gene product is
      most similar to an acyl-CoA dehydrogenase from Novosphingobium aromaticivorans.
      The enzyme encoded by the idoA gene is essential for the metabolism of
      fluoranthene, since a mutant in which the idoA gene has been disrupted looses the
      ability to degrade this compound. The idoA gene appears to be constitutively
      expressed in PA-10, but its expression is also subject to regulation following
      prior exposure to salicylate and to fluoranthene degradative intermediates.

PMID- 15476979
TI  - Factors contributing to the potency of antimicrobial cationic peptides from the N
      terminal region of human lactoferrin.
AB  - This study investigated the antimicrobial activities of peptides derived from the
      N-terminal region of human lactoferrin, and examined the contributions of
      individual residues to the activity of the most potent peptide. Two regions of
      antimicrobial activity were identified, the first corresponding to a weakly
      active peptide, HLP-9, comprising residues 1-9, and a second corresponding to a
      more potent peptide, HLP-10, comprising residues 18-26 and containing the
      hexapeptide motif, FQWQRN. Inhibitory studies on peptides from the first region
      confirm the importance of tryptophan residues in enhancing and broadening peptide
      activity. Inhibitory studies with glycine-substituted homologues of the more
      potent peptide showed that F21/G and R25/G substitutions resulted in a major
      reduction or complete loss of activity, while increased peptide cationicity or
      flexibility had little effect. Our findings demonstrate that F21 and R25 are
      critical determinants of potency for HLP-10, and that the second aromatic residue
      may act synergistically with W23 in developing and enhancing the activity of this
      cationic peptide.

PMID- 15476980
TI  - Kinetics of electron transfer between plastocyanin and the soluble CuA domain of
      cyanobacterial cytochrome c oxidase.
AB  - It has been shown that efficient functioning of photosynthesis and respiration in
      the cyanobacterium Synechocystis PCC 6803 requires the presence of either
      cytochrome c6 or plastocyanin. In order to check whether the blue copper protein
      plastocyanin can act as electron donor to cytochrome c oxidase, we investigated
      the intermolecular electron transfer kinetics between plastocyanin and the
      soluble CuA domain (i.e. the donor binding and electron entry site) of subunit II
      of the aa3-type cytochrome c oxidase from Synechocystis. Both copper proteins
      were expressed heterologously in Escherichia coli. The forward and the reverse
      electron transfer reactions were studied yielding apparent bimolecular rate
      constants of (5.1+/-0.2) x 10(4) M(-1) s(-1) and (8.5+/-0.4) x 10(5) M(-1) s(-1),
      respectively (20 mM phosphate buffer, pH 7). This corresponds to an apparent
      equilibrium constant of 0.06 in the physiological direction (reduction of CuA),
      which is similar to Keq values calculated for the reaction between c-type
      cytochromes and the soluble fragments of other CuA domains. The potential
      physiological role of plastocyanin in cyanobacterial respiration is discussed.

PMID- 15476981
TI  - Heterologous expression of alkene monooxygenase components from Xanthobacter
      autotrophicus Py2 and reconstitution of the active complex.
AB  - The coupling protein and ferredoxin from Xanthobacter autotrophicus Py2 alkene
      monooxygenase (Xamo) have been functionally expressed in both N-terminal affinity
      tagged fusion and native forms in Escherichia coli. However, attempts to express
      the NADH-oxidoreductase and oxygenase, always resulted in the production of
      inactive, insoluble proteins. Nevertheless, the recombinant reductase from the
      toluene 4-monooxygenase of Pseudomonas mendocina KR1 was found to functionally
      complement the Xamo system. In vitro reconstitution, using the recombinant
      coupling protein and other components purified from the wild type, showed that
      steady-state epoxidation rate and coupling efficiency were dependent on the
      relative concentration of Xamo components in the reaction. The optimal molar
      stoichiometric ratio of Xamo components was determined to be approximately 1:0.25
      0.3:2:2 (oxygenase hexamer:reductase:ferredoxin:coupling protein), suggesting the
      formation of an efficient catalytic complex at the minimal stoichiometric ratio
      to saturate the probable two-fold symmetry binding sites on the oxygenase.

PMID- 15476982
TI  - Ocurrence of the antibiotic producing bacterium Burkholderia sp. in colonies of
      the leaf-cutting ant Atta sexdens rubropilosa.
AB  - Fungus garden material from recently established Atta sexdens rubropilosa
      colonies (6-12 months old) was sampled to detect antibiotic producing
      microorganisms that inhibited the growth of pathogens of insects and of the
      fungus gardens but did not affect their mutualistic fungus. A bacterium with
      activity against the entomopathogenic fungus Beauveria bassiana was isolated from
      56% of the gardens tested (n=57) and identified from its biochemical profile and
      from 16S and 23S ribosomal DNA sequences as a member of the genus Burkholderia.
      The ant-associated Burkholderia isolates secreted a potent, anti-fungal agent
      that inhibited germination of conidia of the entomopathogenic fungi B. bassiana,
      Metarhizium anisopliae, of the saprophytic Verticillium lecanii, and also of a
      specialist fungus garden Escovopsis weberi. Growth of the ant's mutualist fungus
      was unaffected.

PMID- 15476983
TI  - Communication in general practice: the Second Dutch National Study.

PMID- 15476984
TI  - Cancer peer support programs-do they work?
AB  - Cancer can be a devastating diagnosis, creating social, emotional, financial and
      psychological problems. Peer support programs are based on the premise that
      support from others who have been through a similar experience can help reduce
      the negative impacts of this disease. While there is strong theoretical rationale
      for this, empirical evidence that would guide program planning is scarce. We
      conducted a systematic literature review of evaluation studies published over the
      last 20 years. Seventeen volunteers delivered peer support programs were
      reviewed, ranging from needs assessments to randomized controlled trials. The
      scientific quality was moderate--most lacked a theoretical framework, adequate
      program descriptions, data on non-participants and validated instruments. Despite
      these methodological shortcomings, consistent informational, emotional and
      instrumental benefits were identified. We provide recommendations for
      practitioners to improve evaluation studies and suggest a research agenda to
      develop better methods for assessing the contribution of peer support to quality
      of life.

PMID- 15476985
TI  - Pediatric residents' response to ambiguous words about child discipline and
      behavior.
AB  - Frequently, doctors have been noted to seemingly ignore or brush off patients'
      bids to discuss sensitive issues. In some of these cases, however, apparent
      ignoring could be the result of the doctor mistakenly interpreting the meaning of
      potentially ambiguous terms used by the patient. This study demonstrates the
      frequency with which parents use and pediatricians clarify ambiguous terms
      describing child behavior and physical punishment. Sixty-one (26%) of 234
      audiotapes from a systematic cross-sectional sample of non-urgent visits with
      pediatric residents included at least one episode in which such words were used
      by a parent. Discussion following each use was classified as: (a) clarifying its
      meaning, (b) discussing without clarification, (c) ignoring the use of the word,
      or (d) contradicting the negative attribution. In 61 visits, the parent or child
      was the first to use the potentially ambiguous term. Physicians clarified 7 (11%)
      of the terms, ignored 23 (38%), contradicted 7 (11%), and discussed without
      clarification 24 (39%). Clarifying and contradicting were associated with a
      shorter doctor-patient relationship than ignoring or discussing without
      clarification. Doctors who sought clarification were the least dominant. A non
      dismissive response to ambiguous words may be a marker for both the stage of the
      doctor-patient relationship and a doctor's overall interactive style. Considering
      clarification may be helpful in understanding doctors' responses to patients'
      cues.

PMID- 15476986
TI  - Using a Values Discussion Guide to facilitate communication in advance care
      planning.
AB  - The utility of values clarification tools for advance care planning needs further
      study. This descriptive, qualitative study aimed to describe patients' and
      surrogates' experiences using a Values Discussion Guide (VDG), both with and
      without a professional facilitator. Ten male Veterans Health Administration
      outpatients over age 50 and their health care agents completed audio-taped
      discussions, both without and with a facilitator, and responded to structured
      feedback interviews. Most participants found a discussion using the VDG to be
      helpful and reassuring. Discussions varied in quantity and quality, and
      participants varied in preferring self-guided versus professionally facilitated
      discussions. The best interchanges were elicited by questions about prior
      experience with medical decisions, for oneself or others, and trusted versus non
      trusted others to help with decision-making. A VDG appears a useful tool in a
      repertoire of advance care planning tools, which need to be geared towards the
      needs and abilities of particular patients and families.

PMID- 15476987
TI  - Towards better communication in cancer care: a framework for developing evidence
      based interventions.
AB  - Increasing recognition of the complexity and difficulty of communication in
      patient care has led to a burgeoning but chaotic literature that tends to be
      incomplete on any one topic. A co-ordinated, planned approach is required to
      facilitate the rapid development and implementation of evidence-based
      interventions in this area. We propose a seven-stage model of communication
      research that is designed to provide clear directions to improve communication in
      cancer care. The stages are: (1) identification of communication difficulties;
      (2) documentation of patient and clinician views; (3) identification of practices
      associated with better outcomes; (4) the development of evidence-based guidelines
      and interventions; (5) testing the effectiveness of the intervention in changing
      current practice and improving patient outcomes; (6) dissemination of the
      effective interventions; and (7) broad adoption of the intervention. Examples are
      provided for each stage of research to elucidate the type of study proposed.

PMID- 15476988
TI  - Cardiovascular risk factors and motivation for a healthy life-style in a German
      community--results of the GP-based Oestringen study.
AB  - This paper explores the motivation of patients towards a healthy life-style in a
      small community with a special general practice and community-based health
      education program in order to identify reasons for different motivations and
      barriers and to improve preventive measures and outcome. The last of six
      standardised health surveys carried out over 9 years in the five general
      practices was therefore combined with a questionnaire to explore the attitudes of
      a sample of patients from these practices (N = 1044) and all attendees of 11
      health education courses (N = 153). In addition to the cardiovascular risk
      factors, data were collected on sociodemographic factors and motivations for
      health promotion. The results show that, over time, the risk factors of
      hypertension (P < 0.001) and smoking (P < 0.005) had decreased. Health-promoting
      activities were not associated with cardiovascular risk factors; the motivations
      "duty" and "staying young" correlated with gender (P < 0.05). Patients with good
      health and white collar professions were more active. About 20% specified
      specific barriers to health-related activities. As expected, the participants of
      an educational program were more highly motivated by "fun", "fitness" and
      "meaningfulness". This group was mainly female. Future preventive measures should
      take into account that motivation for health promotion depends more on
      psychosocial factors than on risk factors; frequent obstacles should be noticed
      in the community.

PMID- 15476989
TI  - Health education on self-management and seeking health care in older adults: a
      randomised trial.
AB  - The aim of this randomised trial was to determine the effects of a health
      education strategy for older adults living at home on GP attendance. The health
      education comprised a written booklet on five frequently by GP unnoticed, highly
      prevalent and potentially treatable health problems: hearing impairment, visual
      impairment, urinary incontinence, depression and Lower Urinary Tract Symptoms
      (LUTS). The information comprised structured guidance to enhance decision-making
      on seeking health care by their GP and contained advice on self-management. The
      control group did not receive any intervention. Primary outcome was GP attendance
      of patients regarding the five health problems within 3 months. At this point we
      expected an increase of GP attendance. Six hundred and eighty-seven subjects
      completed the study. We can conclude that the health education strategy did not
      change the GP attendance of older adults. The results suggest that the health
      education was being appreciated as being useful and informative.

PMID- 15476990
TI  - Evaluation of an evidence-based education package for men with prostate cancer on
      hormonal manipulation therapy.
AB  - Prostate cancer has become a public health problem worldwide with considerable
      social and economic consequences. Many men have extraprostatic spread at
      diagnosis, and treatment usually involves hormonal manipulation therapy, which
      can challenge the stereotypical male image. It is often assumed that merely the
      provision of educational material for patients in an accessible form is
      sufficient to address informational needs. However, with the increasing emphasis
      on evidence-based practice, an essential element of the patient education process
      is evaluation of the impact of educational interventions. In this study, a
      randomised controlled trial was used to evaluate the effect of an evidence-based
      education package on the knowledge of disease and treatment, quality of life,
      coping and satisfaction of a sample (n=55) of men with prostate cancer on
      hormonal manipulation therapy in the UK. The men were randomly assigned to
      experimental (n=28) and control group (n=27). Established instruments with
      satisfactory reliability and validity were used to measure the dependent
      variables. The independent variable, namely the education package, had been
      developed following the results of a previous study, which assessed the
      informational needs of this client group. This package consisted of an
      information booklet supplemented by the verbal teaching of a urology nurse.
      Results demonstrated that delivery of the education package had a significant
      effect on knowledge, quality of life and satisfaction with care, but not on
      coping. This study has contributed to the evidence-base for practice in
      urological nursing. This education package should become a routine, and not
      merely incidental aspect of care for this client group.

PMID- 15476991
TI  - Evaluation of a community rehabilitation service for people with rheumatoid
      arthritis.
AB  - This study aims to evaluate the outcomes of a community rehabilitation service
      for people with rheumatoid arthritis, provided by the Community Rehabilitation
      Network (CRN) in Hong Kong. The three-phase community rehabilitation service
      consists of a number of standardized program elements, including orientation
      meeting, self-help course, stress management program, water exercises class, as
      well as informal social and recreational activities. Using a pre-, post-test non
      equivalent groups design, the outcomes of 29 clients of the treatment group were
      compared with 16 clients of the comparison group at baseline and at the end of 9
      months, using an 86-item self-completed questionnaire. The treatment group
      achieved significant more increases in self-efficacy of managing the illness,
      more increases in self-management behaviors, but no significant increases in the
      overall health status or health care utilization patterns, when compared with the
      comparison group.

PMID- 15476992
TI  - A prospective study of the use of alternative therapies by men with localized
      prostate cancer.
AB  - Although the use of alternative therapies is highly prevalent amongst men with
      prostate cancer, research about the predictors of such use is limited. The
      current study aimed to describe prospectively the use of alternative therapies by
      men diagnosed with localized prostate cancer and identify predictors of
      alternative therapy use. In all, 111 men newly diagnosed with localized prostate
      cancer (93% response) were recruited to the study prior to treatment. Men's use
      of alternative therapies and psychological variables including: psychological
      distress, orientation to health care, decisional conflict, and health locus of
      control, were assessed at three time points-(1) before treatment; (2) 2 months
      after completion of treatment; and (3) 12 months after completion of treatment.
      Demographic information was also obtained. The percentage of men using
      alternative therapies was 25, 17 and 14% before treatment, 2 and 12 months after
      treatment, respectively. In general, the most commonly used therapies were
      dietary changes, vitamins and herbal and nutrient remedies. Alternative therapy
      use was not related to final treatment choices. Before treatment, men who used
      alternative therapies were more uncertain about prostate cancer compared to men
      who were not using these therapies. Men who were using alternative therapies 12
      months after treatment were less psychologically distressed that men who were not
      using these therapies. Health locus of control and orientation to health care
      were not found to be related to men's use of alternative therapies. In
      conclusion, men's use of alternative therapies after localized prostate cancer
      varied across time in terms of the incidence of use, the types of therapies used,
      and the psychological correlates of therapy use. Informational support that
      targets uncertainty about prostate cancer may assist men at diagnosis who are
      considering alternative therapy use. The potential for alternative therapies to
      have a supportive function in patient care requires further investigation.

PMID- 15476993
TI  - Development and pilot testing of a disease management program for low literacy
      patients with heart failure.
AB  - Development and pilot testing of a disease management program for low literacy
      patients with heart failure. BACKGROUND: Randomized trials have shown that
      disease management programs can reduce hospitalizations and improve symptoms for
      patients with congestive heart failure. We sought to create and pilot test such a
      program for patients with low literacy skills. METHODS: We used focus groups and
      individual cognitive response interviews (CRIs) to develop an educational booklet
      for low literacy patients with heart failure. We incorporated the booklet into a
      disease management intervention that also included an initial individualized 1-h
      educational session and scheduled supportive phone calls that were tapered over 6
      weeks. We then conducted a 3-month before-after study on patients with low
      literacy skills (<9th grade literacy level) in a university internal medicine
      clinic to test the acceptability and efficacy of our program. Outcomes of
      interest included heart failure-related knowledge, self-care behavior and heart
      failure-related symptoms measured on the Minnesota Living with Heart Failure
      (MLwHF) scale. RESULTS: Twenty-five patients were enrolled and 23 (92%) completed
      3-month follow-up. Mean age was 60 years (range 35-74), 60% were men, 60% were
      African-American, and 74% had household income under $15,000 per year. The median
      reading level was fifth grade with 32% reading at or below the third grade level.
      Mean knowledge score at baseline was 67% and did not improve after the
      intervention. The proportion of patients reporting weighing themselves daily
      increased from 32% at baseline to 100% at 12 weeks. Mean improvement on the MLwHF
      scale was 9.9 points over the 3-month trial (95% CI: 0.5, 19.2), which
      corresponds to an improvement in one class on the New York Heart Association
      heart failure scale. CONCLUSION: A heart failure disease management program
      designed specifically for patients with low literacy skills is acceptable and is
      associated with improvement in self-care behavior and heart failure related
      symptoms.

PMID- 15476994
TI  - Experience, functions and benefits of a cancer support group.
AB  - The limited research which has been conducted in relation to self help as opposed
      to therapeutic cancer support groups has produced conflicting findings. In
      response the current study approached three local cancer support groups and
      requested their involvement in a qualitative study incorporating focus group
      discussion. Results revealed that the variation in psychological well being and
      coping experienced by individual members influenced subsequent preferences for
      support, information and involvement. Members therefore used a variety of sources
      of support and information throughout their care. An example of this was
      membership of the local cancer support group. These groups provided practical
      assistance, emotional support, a sense of belonging and realistic information
      relating to the "normal" course of the illness. However, use of these functions
      varied between individuals and highlighted the need to evaluate these groups not
      in relation to their provision of group therapy but in relation to the individual
      experiences of each member.

PMID- 15476995
TI  - Copying referral letters to patients: the views of patients, patient
      representatives and doctors.
AB  - To discover the views of patients, patient representatives and doctors on copying
      referral letters to patients. A three-part study: an analysis of 50 GP referral
      letters against a standard template; 35 patient interviews using a semi
      structured questionnaire in outpatient waiting rooms; 3 focus groups of patients,
      patient representatives and doctors. There was general agreement that copying
      referral letters to patients could improve information and decision sharing with
      patients. Copying referral letters could provide an opportunity for patients to
      correct mistakes, prepare for their appointments and have a personal record that
      they could keep and show to others. However, there were concerns about letter
      content, particularly medical terminology, character judgements and "sensitive"
      patient information. It was also recognised that providing more information to
      patients could increase patient anxiety. The style and content of some referral
      letters may need to change. This is particularly relevant where certain types of
      information included in referral letters could cause distress for patients or
      influence the time that patients have to wait for their outpatient appointments.

PMID- 15476996
TI  - The development of a psychoeducational intervention for women living with an
      increased risk of breast cancer.
AB  - Research has shown a widespread need for written information on topics related to
      familial risk of breast cancer amongst women who have been living with an
      increased risk of the disease for several years. This article describes the
      development of a psychoeducational intervention designed to meet the needs of
      these women. Following a review of the literature and existing information
      resources, a multidisciplinary group developed a written information pack
      consisting of scientific and psychosocial (self-help) information with the aim of
      improving knowledge and reducing cancer worry. The information pack has been
      evaluated by seven independent health professionals and piloted on eight women at
      increased risk of breast cancer. Aspects of readability and presentation have
      been considered. The results of a randomised controlled trial of the
      intervention, which will inform the current provision of clinical services for
      these women, will be reported elsewhere.

PMID- 15476997
TI  - Assessing patients' participation and quality of decision-making: insights from a
      study of routine practice in diverse settings.
AB  - In the context of a qualitative study exploring patients' participation in
      decision-making, we investigated how people interpret and respond to structured
      questions about decision-making about their health care. Seventy-four
      participants who attended consultations in five clinical areas completed
      structured measures of decision-making and discussed their responses during
      interviews. They identified a range of decisions as having being made in their
      consultations. People who picked particular responses on measures of
      participation in and satisfaction with decision-making gave varied explanations
      for these, not all of which were consistent with the way their responses are
      usually interpreted. The interview data suggest that people's evaluations of
      decisions to follow a particular course of action were influenced by various
      factors including what they focused on as the alternative, their perceptions of
      constraints on choices, and their assessment of how good the best possible
      solution was. Responses to simple structured measures of participation in and
      satisfaction with decision-making should be interpreted with caution. They are
      not reliably attributable to health care providers' actions and are thus
      unsuitable for performance assessment purposes.

PMID- 15476998
TI  - Effect of education on self-efficacy of Turkish patients with chronic obstructive
      pulmonary disease.
AB  - This study was designed to compare the effect of structured education on self
      efficacy in patients with chronic obstructive pulmonary disease (COPD). The study
      was carried out with an experimental group on which a structured education was
      provided, and a control group on which only educational advice was provided.
      There were 30 patients in both groups. Control and experimental group
      measurements were obtained on the COPD Self-Efficacy Scale (CSES). There was a
      significant difference between control group and experimental group scores on the
      CSES. Self-efficacy, as it affects managing or avoiding breathing difficulty, was
      measured before and after the structured education program and the nursing care.
      Patients' self-efficacy scores significantly improved after the structured
      education and remained significantly improved 1-month later. Standard nursing
      care alone was also effective in significantly improving self-efficacy scores,
      but patients' scores 1-month later were not significantly better than pre-program
      scores. This study indicates that a planned education program that is more
      effective in improving self-efficacy in patients with COPD.

PMID- 15476999
TI  - Effectiveness of an education programme by a general practice assistant for
      asthma and COPD patients: results from a randomised controlled trial.
AB  - In this study a randomised controlled trial was carried out to investigate the
      effectiveness of an education programme for patients with asthma or chronic
      obstructive pulmonary disease (COPD). All asthma and COPD patients using
      medication and experiencing pulmonary symptoms were randomly assigned to the
      intervention (n=139) or usual-care group (n=137). The intervention consisted of
      taylor-made education conducted by a general practice assistant and focussing on
      a patients' technical skills and coping with the disease. Measurements took place
      at baseline, and after 1 and 2 years of follow-up. After 1 and 2 years the
      inhalation technique was significantly better in the intervention group compared
      to the usual-care group. No significant differences were observed regarding
      disease symptoms, health related quality of life, compliance, smoking cessation,
      self-efficacy, and coping. The results only support the implementation of the
      intervention regarding the technical skills (inhalation technique). However,
      given the importance of improvement of patients' coping and the need for more
      efficient care, we recommend further exploration of the possibilities of a more
      structured and intensive education programme.

PMID- 15477000
TI  - Emergency contraceptive pills over-the-counter: practices and attitudes of
      pharmacy and nurse-midwife providers.
AB  - Deregulation of emergency contraceptive pills (ECP) has led to pharmacy staff
      becoming a new provider group of ECP, together with nurse-midwives, who are
      already experienced in prescribing contraceptives. This postal questionnaire
      survey aimed to assess practices and attitudes towards ECP and the over-the
      counter (OTC)-availability among pharmacy staff (n=237) and nurse-midwives
      (n=163). The overall response rate was 89%. Both study groups were positive to
      ECP and the OTC-availability and the vast majority agreed that sexually active
      women should be aware of ECP and that routine information about ECP should be
      included in contraceptive counseling. Verbal information on all aspects of ECP to
      clients was reported more often by nurse-midwives than by pharmacy staff. Both
      groups supported collaboration between providers. Our findings suggest that
      further collaboration between pharmacies and family planning clinics should be
      encouraged to ensure a competent and client-friendly provision of ECP.

PMID- 15477001
TI  - Targeting pupils at risk of occupational asthma.
AB  - A cross-sectional study was carried out in pupils attending the last training
      year from three school sections with high risks of occupational asthma
      (hairdressing, wood's profession, bakery) and in two groups with lower risks
      (butcher, salesmen). The analysis concerns a representative sample of 533 pupils
      in the French-speaking Community of Belgium. Among them, 62.0% in high risk
      professions of occupational asthma (OA) are conscious of occupational risks
      related to their work, as were 52.1% of those in professions less at risk (P <
      0.05). The difference is also significant when asthma is mentioned as a health
      problem: 12.6% of the bakers and 14.1% of the hairdressers declared having
      suffered from asthma and 21.4% of the bakers and 26.7% of the hairdressers
      reckoned having had wheezing in their chest over the last 12 months. These
      results report preliminary signs of asthma in pupils before entering in their
      active life with risk of OA. Primary prevention should include information and
      redirecting pupils at risk of developing or increasing the disease in their
      working environment.

PMID- 15477002
TI  - Assessing inpatients' satisfaction with hospital care: should we prefer
      evaluation or satisfaction ratings?
AB  - Inpatients' satisfaction with hospital care is often assessed by questionnaire.
      From a psychometrical standpoint, this method has drawbacks, however. We further
      investigated which item response format would maximise desirable outcomes
      regarding characteristics of the sample obtained (response rate and
      representativeness) and psychometric properties of the instrument (e.g. missing
      items responses, variance, validity) as an initial study into this question was
      indecisive. Subjects were 1184 discharged inpatients, of which 728 patients (62%)
      responded. They filled out a 55-item satisfaction questionnaire, addressing 12
      aspects of care, using either a 10-point Evaluation scale ranging from "very
      poor" to "excellent" (E10) or a 5-point Satisfaction scale ranging from
      "dissatisfied" to "very satisfied" (S5). Both E10 and S5 showed good psychometric
      properties, but S5 yielded a better score distribution. Other results also
      favoured S5, but differences were small. In conclusion, different response
      formats do not yield widely different results. Thus, in choosing between them,
      convenience could be a decisive factor.

PMID- 15477003
TI  - Genetically altered mice to evaluate glutathione homeostasis in health and
      disease.
AB  - The tripeptide glutathione (GSH) is part of an integrated antioxidant system that
      protects cells and tissues from oxidative damage. Oxidative stress can result
      from exposure to excessive amounts of endogenous and exogenous electrophiles.
      Until recently, animal and cell model systems used to investigate the role of GSH
      in disease processes had employed chemical agents that deplete cellular GSH by
      inhibiting GSH synthesis or by reacting chemically with GSH. Such models have
      proven useful, but questions concerning nonspecific effects of such chemicals
      remain. Recently, our laboratories and others have developed mouse models with
      genetic deficiencies in enzymes of the GSH biosynthetic pathway. This review
      focuses on the regulation of GSH homeostasis and, specifically, the new GSH
      deficient mouse models that have been developed. These models will improve our
      understanding of the role of GSH in animal and human diseases.

PMID- 15477004
TI  - Particulate phase cigarette smoke increases MnSOD, NQO1, and CINC-1 in rat lungs.
AB  - Loss of antioxidant/oxidant homeostasis perpetuates inflammation in the lungs and
      may contribute to the development of COPD and lung cancer. Cigarette smoke (CS)
      is a primary source of airway oxidative stress and recruits inflammatory cells
      into smokers' lungs. However, whether these consequences are attributable to a
      specific or the collective fraction of CS is unknown. We investigated whether the
      particulate or the gas phase of CS would alter expression of the antioxidant
      enzymes MnSOD and NQO1 or CINC-1. Sprague Dawley rats were exposed to sham (n =
      10) or the particulate phase (PP; n = 10) or gas phase (n = 10) of a Kentucky
      reference cigarette (1R4F) for 2 h/d for 28 d, after which animals were
      sacrificed and the lower left lobe of the lung was removed. Immunoblots for SOD
      and NQO1 revealed that lungs exposed to PP had higher MnSOD/actin and NQO1/actin
      ratios than either sham-or gas phase-treated animals. In contrast, CuZnSOD
      remained unchanged. In PP-exposed animals, CINC-1 was 3-fold higher than in sham
      exposed animals. The increases in MnSOD and NQO1 protein were associated with
      increases in total SOD, NQO1, and MPO activities. These data provide evidence
      that the PP of CS alters oxidant/antioxidant homeostasis in the lungs and
      participates in the pathogenesis of CS-induced lung diseases such as COPD and
      cancer.

PMID- 15477005
TI  - Cellular 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase
      activity of human and mouse MTH1 proteins does not depend on the proliferation
      rate.
AB  - Mammalian MTH1 proteins, homologs of Escherichia coli MutT, are enzymes
      decomposing 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) to 8
      oxo-7,8-dihydro-2'-deoxyguanosine 5'-monophosphate and inorganic pyrophosphate.
      They play an antimutagenic role by preventing the incorporation of promutagenic 8
      oxo-dGTP into DNA. MTH1 gene expression is higher in some physiological types of
      mammalian cells and in numerous cancer cells, but the mechanism of that
      upregulation still remains unclear. It has been hypothesized that MTH1 expression
      might be associated with a proliferation rate of the cells. Therefore, we tested
      this hypothesis by comparing the functional levels of MTH1 gene expression
      measured as the 8-oxo-dGTPase activity of its protein products in normal mouse
      livers and hepatectomized regenerating livers. Although the proliferation rate of
      the hepatocytes in the regenerating livers was much higher than that in control
      livers, as confirmed by immunohistochemical assay of proliferating cell nuclear
      antigen, the 8-oxo-dGTPase activity was not different. In a second approach, we
      used 57 lines of human cancer cells in which 8-oxo-dGTPase activity was measured
      and confronted with cell population doubling time. No significant correlations
      between 8-oxo-dGTPase activity and proliferation rate were observed within groups
      of six leukemia, eight melanoma, nine lung, seven colon, six central nervous
      system, six ovarian, eight renal, and seven breast cancer cell lines. Thus, we
      conclude that the MTH1 expression manifested as the 8-oxo-dGTPase activity of its
      protein products in mammalian cells is not associated with proliferation rate.
      Our results will help in further testing of the hypothesis that MTH1
      overexpression may be a specific marker of carcinogenesis and/or oxidative
      stress.

PMID- 15477006
TI  - Functional association of nox1 with p22phox in vascular smooth muscle cells.
AB  - The vascular NAD(P)H oxidases constitute important sources of ROS in the vessel
      wall and have been implicated in vascular disease. Vascular smooth muscle cells
      (VSMCs) from conduit arteries express two gp91phox homologs, Nox1 and Nox4, of
      which Nox1 is agonist-sensitive. Because p22phox has been shown to be
      functionally important in vascular cells stimulated with vasoactive hormones, the
      relationship of Nox1 and p22phox was investigated in VSMCs from rat and human
      aortas. Coimmunoprecipitation studies demonstrated that p22phox and hemagglutinin
      tagged Nox1 associate in unstimulated VSMCs. These findings were confirmed by
      confocal microscopy, showing colocalization of the two proteins in their native
      states in the plasma membrane and submembrane areas of the cell. NADPH-driven
      superoxide production, as measured by electron spin resonance using 1-hydroxy-3
      carboxypyrrolidine as a spin probe, is dependent on the coexpression of both
      subunits, suggesting the importance of the association for the functional
      integrity of the enzyme. These results indicate that in contrast to the
      neutrophil enzyme, VSMCs can use Nox1 rather than gp91phox as a catalytic center
      in the p22phox-based oxidase and that these two proteins are preassembled at or
      near the plasma membrane and submembrane vesicular structures in unstimulated
      cells.

PMID- 15477007
TI  - Effects of a redox-active agent on lymphocyte activation and early gene
      expression patterns.
AB  - Antioxidants can inhibit the proliferation of T lymphocytes induced by mitogens.
      This has been postulated to be due to their scavenging of reactive oxygen species
      which may act as second messengers in the antigen-induced signaling cascade
      leading to cell proliferation. When added concurrently with various mitogens, the
      thiol pyrrolidine dithiocarbamate (PDTC) inhibited the subsequent proliferation
      of lymphocytes. The extracellular copper chelator bathocuproine disulfonic acid
      (BCPS) increased the amount of PDTC needed for inhibition. We sought to determine
      the mechanism by which the two different treatments, PDTC (0.4 microM, copper
      dependent) and PDTC (20 microM with BCPS, redox-sensitive) affected
      proliferation. We found that both inhibited the increase in expression of many of
      the genes, including IL-2 and MKP-2, that were induced early after stimulation of
      lymphocytes with phorbol myristate acetate and ionomycin. The inhibition of MKP-2
      may have contributed to the enhancement observed by the thiol of mitogen-induced
      ERK phosphorylation. Of the two redox-sensitive, IL-2 regulating transcription
      factors, NF-kappaB and AP-1, the mitogen-induced activity of the former was
      inhibited by PDTC. Treatment of unstimulated cells with PDTC induced the
      expression of many genes, most notably several metallothioneins and heat shock
      proteins, and this may provide an alternative explanation for the inhibition of
      cellular proliferation.

PMID- 15477008
TI  - Reevaluating gel-forming mucins' roles in cystic fibrosis lung disease.
AB  - The existence of mucus plugs, containing mucins, bacteria, and neutrophils,
      blocking the lower airways in the lung of cystic fibrosis (CF) patients has
      raised the possibility that production of "abnormal" mucins is a critical
      characteristic of this disease. The molecular nature, if any, of this abnormality
      is unknown. Recent studies suggest that CF lung disease progression is
      characterized by an early phase in which airway surface liquid (ASL) increased
      dehydration is accompanied by altered pH and levels of reduced glutathione (GSH).
      In a later phase, bacterial infection and neutrophil invasion lead to increased
      ASL of concentrations myeloperoxidase and hypochlorous acid (HOCl). Independent
      studies indicate that gel-forming mucins, the key components of airway mucus,
      form disulfide-linked polymers through a pH-dependent, likely self-catalyzed
      mechanism. In this article, we present the hypothesis that increased mucus
      concentration (dehydration) and altered pH, and levels of GSH, myeloperoxidase,
      and/or HOCl result in the extracellular formation of additional interchain bonds
      among airway mucins. These novel interactions would create an atypical mucin
      network with abnormal viscoelastic and adhesive properties.

PMID- 15477009
TI  - Induction of detoxifying enzymes by garlic organosulfur compounds through
      transcription factor Nrf2: effect of chemical structure and stress signals.
AB  - Garlic organosulfur compounds (OSCs) are recognized as a group of potential
      chemopreventive compounds. It is known that garlic OSCs can modulate drug
      metabolism systems, especially various phase II detoxifying enzymes, though the
      mechanism underlying their inductive effect on these enzymes remains largely
      unknown. In the present study, we investigated the transcriptional levels of
      NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO1) genes, the
      reporter activity mediated by antioxidant response element (ARE), and the protein
      level of transcription factor nuclear factor E2-related factor 2 (Nrf2), after
      administration of three major garlic OSCs--diallyl sulfide (DAS), diallyl
      disulfide (DADS), and diallyl trisulfide (DATS)--in human hepatoma HepG2 cells.
      Our results showed that ARE activation and Nrf2 protein accumulation were well
      correlated with phase II gene expression induction. The structure-activity
      relationship study indicated that the third sulfur in the structure of OSCs
      contributed substantially to their bioactivities, and that allyl-containing OSCs
      were more potent than propyl-containing OSCs. To better understand the signaling
      events involved in the upregulation of detoxifying enzymes by DATS, ARE activity
      and Nrf2 protein levels were examined after transient transfection of HepG2 cells
      with mutant Nrf2, cotreatment with antioxidants, and pretreatment with protein
      kinase inhibitors. DATS-induced ARE activity was inhibited by dominant-negative
      Nrf2 Kelch-like ECH-associating protein 1 and constructs. Cotreatment with thiol
      antioxidants decreased the ARE activity and Nrf2 protein level induced by DATS.
      Three major mitogen-activated protein kinases (MAPKs)--extracellular signal
      regulated protein kinase, c-Jun N-terminal kinase, and p38--were activated by
      DATS treatment. However, the inhibition of these MAPKs did not affect DATS
      induced ARE activity. Pretreatment with various upstream protein kinase
      inhibitors showed that the protein kinase C pathway was not directly involved in
      DATS-induced ARE activity, but instead the calcium-dependent signaling pathway
      appeared to play a role in the DATS-induced cytoprotective effect.

PMID- 15477010
TI  - Involvement of protein radical, protein aggregation, and effects on NO metabolism
      in the hypochlorite-mediated oxidation of mitochondrial cytochrome c.
AB  - Cytochrome c (cyt c)-derived protein radicals, radical adduct aggregates, and
      protein tyrosine nitration have been implicated in the pro-apoptotic event
      connecting inflammation to the development of diseases. During inflammation, one
      of the reactive oxygen species metabolized via neutrophil activation is
      hypochlorite (HOCl); destruction of the mitochondrial electron transport chain by
      hypochlorite is considered to be a damaging factor. Previous study has shown that
      HOCl induces the site-specific oxidation of cyt c at met-80. In this work, we
      have assessed the hypothesis that exposure of cyt c to physiologically relevant
      concentrations of HOCl leads to protein-derived radical and consequent protein
      aggregation, which subsequently affects cyt c's regulation of nitric oxide
      metabolism. Reaction intermediates, chemical pathways available for protein
      aggregation, and protein nitration were examined. A weak ESR signal for
      immobilized nitroxide derived from the protein was detected when a high
      concentration of cyt c was reacted with hypochlorite in the presence of the
      nitroso spin trap 2-methyl-2-nitrosopropane. When a low concentration of cyt c
      was exposed to the physiologically relevant levels of HOCl in the presence of 5,5
      dimethyl-pyrroline N-oxide (DMPO), we detected DMPO nitrone adducts derived from
      both protein and protein aggregate radicals as assessed by Western blot using an
      antibody raised against the DMPO nitrone adduct. The cyt c-derived protein
      radicals formed by HOCl were located on lysine and tyrosine residues, with lysine
      predominating. Cyt c-derived protein aggregates induced by HOCl involved
      primarily lysine residues and hydrophobic interaction. In addition, HOCl-oxidized
      cyt c (HOCl-cyt c) exhibited a higher affinity for NO and enhancement of
      nonenzymatic NO synthesis from nitrite reduction. Furthermore, HOCl-mediated cyt
      c oxidation also resulted in a significant elevation of cyt c nitration derived
      from either NO trapping of the cyt c-derived tyrosyl radical or cyt c-catalyzed
      one-electron oxidation of nitrite.

PMID- 15477011
TI  - Covalent binding of isoketals to ethanolamine phospholipids.
AB  - Free radicals have been strongly implicated in the pathogenesis of many human
      diseases. We previously identified the formation of highly reactive gamma
      ketoaldehydes, isoketals, in vivo as products of free radical-induced
      peroxidation of arachidonic acid. Isoketals react with lysine residues on
      proteins at a rate that far exceeds that of 4-hydroxynonenal and demonstrate a
      unique proclivity to crosslink proteins. Hydroxynonenal has been shown to react
      with aminophospholipids, particularly phosphatidylethanolamine. We explored
      whether isoketals also react with phosphatidylethanolamine. Using liquid
      chromatography/electrospray mass spectrometry, we found that isoketals form
      pyrrole and Schiff base adducts with phosphatidylethanolamine. In addition, the
      ability of isoketals to covalently modify phosphatidylethanolamine is greater
      than that of 4-hydroxynonenal. These studies identify in vitro novel isoketal
      adducts. This provides the basis to explore the formation of isoketal
      aminophospholipid adducts in vivo and the biological consequences of the
      formation of these adducts.

PMID- 15477012
TI  - Ascorbic acid recycling by cultured beta cells: effects of increased glucose
      metabolism.
AB  - Ascorbic acid is necessary for optimal insulin secretion from pancreatic islets.
      We evaluated ascorbate recycling and whether it is impaired by increased glucose
      metabolism in the rat beta-cell line INS-1. INS-1 cells, engineered with the
      potential for overexpression of glucokinase under the control of a tetracycline
      inducible gene expression system, took up and reduced dehydroascorbic acid to
      ascorbate in a concentration-dependent manner that was optimal in the presence of
      physiologic D-glucose concentrations. Ascorbate uptake did not affect
      intracellular GSH concentrations. Whereas depletion of GSH in culture to levels
      about 25% of normal also did not affect the ability of the cells to reduce
      dehydroascorbic acid, more severe acute GSH depletion to less than 10% of normal
      levels did impair dehydroascorbic acid reduction. Culture of inducible cells in
      11.8 mM D-glucose and doxycycline for 48 h enhanced glucokinase activity,
      increased glucose utilization, abolished D-glucose-dependent insulin secretion,
      and increased generation of reactive oxygen species. The latter may have
      contributed to subsequent decreases in the ability of the cells both to maintain
      intracellular ascorbate and to recycle it from dehydroascorbic acid. Cultured
      beta cells have a high capacity to recycle ascorbate, but this is sensitive to
      oxidant stress generated by increased glucose metabolism due to culture in high
      glucose concentrations and increased glucokinase expression. Impaired ascorbate
      recycling as a result of increased glucose metabolism may have implications for
      the role of ascorbate in insulin secretion in diabetes mellitus and may partially
      explain glucose toxicity in beta cells.

PMID- 15477013
TI  - Chlorine transfer between glycine, taurine, and histamine: reaction rates and
      impact on cellular reactivity.
AB  - Hypochlorous acid formed by activated neutrophils reacts with amines to produce
      chloramines. Chloramines vary in stability, reactivity, and cell permeability. We
      have examined whether chloramine exchange occurs between physiologically
      important amines or amino acids and if this affects interactions of chloramines
      with cells. We have demonstrated transchlorination reactions between histamine,
      glycine, and taurine chloramines by measuring chloramine decay rates with
      mixtures as well as by mass spectrometry. Kinetic analysis suggested the
      formation of an intermediate complex with a high K(m). Apparent second-order rate
      constants, determined for concentrations <K(m), were 19.4, 23.8, 6.0, and 7.5 M(
      1) min(-1) for glycine chloramine (Gly-Cl) and taurine, Gly-Cl and histamine,
      histamine chloramine and glycine, and taurine chloramine (Tau-Cl) and glycine,
      respectively. Thus with 10 mM amine concentrations, half-lives for chloramine
      exchange are on the order of a few minutes. Glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) activity in cells was measured as an indicator of
      permeability of the chloramines. When endothelial or Jurkat cells were treated in
      Hanks' buffer, Gly-Cl inhibited GAPDH, whereas Tau-Cl, which does not penetrate
      the cells, did not. Adding glycine to Tau-Cl brought about inhibition, whereas
      taurine mitigated the effect of Gly-Cl. For cells in full medium, high chloramine
      concentrations were needed to inhibit GAPDH because of scavenging by methionine
      and other constituents. In methionine-free medium, chlorine exchange resulted in
      GAPDH inhibition by Tau-Cl, whereas Gly-Cl was less effective than in Hanks'
      buffer. Thus interchange between chloramines occurs readily and modulates their
      cellular effects.

PMID- 15477014
TI  - Alkaline-earth cations enhance ortho-quinone-catalyzed ascorbate oxidation.
AB  - Ortho-quinones 1,10-phenanthroquinone and beta-lapachone but not para-quinones
      naphthazarin (NZQ) and 1,4-naphthoquinone enhance ascorbate oxidation in the
      presence of MgCl(2) and CaCl(2) at constant ionic strength. Alkaline-earth cation
      chelation is observed for the ortho-semiquinones but not for the para
      semiquinones, while no interaction between these quinones (with the exception of
      NZQ) or ascorbate and these salts was detected, suggesting that semiquinone-metal
      complexes are responsible for the catalytic action on ascorbate oxidation of
      these metal salts in the presence of these ortho-quinones. Thus, redox cycling
      efficiency of the quinones under study here, in the presence of ascorbate,
      depends not only on the quinone redox potential but also on the semiquinone
      ability to chelate alkaline-earth cations.

PMID- 15477015
TI  - Oxygen in the alveolar air space mediates lung inflammation in acute
      pancreatitis.
AB  - During the early stages of acute pancreatitis, acute respiratory distress
      syndrome often occurs. This is associated with the release of proinflammatory
      mediators into the blood, but it remains unclear why these mediators induce
      inflammation especially in the lung. One of the first events occurring during the
      progression of acute pancreatitis is the induction of P-selectin expression in
      the endothelial cells of the lung. This expression has been associated with the
      generation of superoxide radicals by circulating xanthine oxidase. Because this
      enzyme needs molecular oxygen to perform the reaction, we have hypothesized that
      oxygen present in the alveolar space favors the generation of free radicals by
      xanthine oxidase and explains why P-selectin is expressed only in the lung. For
      this purpose, we evaluated the progression of the inflammatory process in rats
      with induced acute pancreatitis and one lung breathing nitrogen while the other
      lung continued breathing air. Acute pancreatitis was induced by intraductal
      administration of taurocholate and myeloperoxidase; P-selectin expression was
      measured 3 h after induction. Results indicated that, in the absence of oxygen in
      the alveolar space, the xanthine oxidase-dependent P-selectin expression did not
      occur and lung inflammation was significantly reduced.

PMID- 15477016
TI  - The effects of antioxidants on radiation-induced apoptosis pathways in TK6 cells.
AB  - This study was designed to determine if radiation-mediated activation of the
      apoptotic pathways would be influenced by antioxidants and if a correlation would
      be found between radioprotection and changes in transduction pathways. Human
      lymphoblastoid TK6 cells, known to undergo apoptosis as a result of radiation,
      were irradiated (6 Gy) with and without antioxidants, and then whole-cell lysates
      were collected. Parallel studies were conducted to assess the survival
      (clonogenic assay) and apoptotic index. The impacts of two nitroxide
      antioxidants, tempol and CAT-1, differing in cell permeability, as well as the
      sulfhydryl antioxidant N-acetyl-L-cysteine (L-NAC), were estimated. Changes in
      apoptotic pathway proteins and p53 were assessed by Western blotting. Fraction of
      apoptotic cells was determined by flow cytometry. Tempol (10 mM), which readily
      enters cells, partially radioprotected TK6 cells against clonogenic killing, but
      had no effect on radiation-induced apoptotic parameters such as cleaved caspase 3
      or cleaved PARP. Tempol alone did not induce cytotoxicity, yet did increase
      cleaved PARP levels. The radiation-induced increase in p53 protein was partly
      inhibited by tempol, but was unaffected by CAT-1 and L-NAC. Both CAT-1 (10 mM),
      which does not enter cells, and L-NAC (10 mM) had no radioprotective effect on
      cell survival. Although L-NAC did not protect against radiation-induced
      cytotoxicity, it completely inhibited radiation-induced increase in cleaved
      caspase 3 and cleaved PARP. Collectively, the results question the validity of
      using selected apoptosis pathway members as sole indicators of cytotoxicity.

PMID- 15477018
TI  - NF-kappaB protects lung epithelium against hyperoxia-induced nonapoptotic cell
      death-oncosis.
AB  - Prolonged exposure to hyperoxia induces pulmonary epithelial cell death and acute
      lung injury. Although both apoptotic and nonapoptotic morphologies are observed
      in hyperoxic animal lungs, nonapoptotic cell death had only been recorded in
      transformed lung epithelium cultured in hyperoxia. To test whether the
      nonapoptotic characteristics in hyperoxic animal lungs are direct effects of
      hyperoxia, the mode of cell death was determined both morphologically and
      biochemically in human primary lung epithelium exposed to 95% O(2). In contrast
      to characteristics observed in apoptotic cells, hyperoxia induced swelling of
      nuclei and an increase in cell size, with no evidence for any augmentation in the
      levels of either caspase-3 activity or annexin V incorporation. These data
      suggest that hyperoxia can directly induce nonapoptotic cell death in primary
      lung epithelium. Although hyperoxia-induced nonapoptotic cell death was
      associated with NF-kappaB activation, it is unknown whether NF-kappaB activation
      plays any causal role in nonapoptotic cell death. This study shows that
      inhibition of NF-kappaB activation can accelerate hyperoxia-induced epithelial
      cell death in both primary and transformed lung epithelium. Corresponding to the
      reduced cell survival in hyperoxia, the levels of MnSOD were also low in NF
      kappaB-deficient cells. These results demonstrate that NF-kappaB protects lung
      epithelial cells from hyperoxia-induced nonapoptotic cell death.

PMID- 15477017
TI  - In vivo protein transduction: biologically active intact pep-1-superoxide
      dismutase fusion protein efficiently protects against ischemic insult.
AB  - Reactive oxygen species (ROS) are implicated in reperfusion injury after
      transient focal cerebral ischemia. The antioxidant enzyme Cu,Zn-superoxide
      dismutase (SOD) is one of the major means by which cells counteract the
      deleterious effects of ROS after ischemia. Recently, we reported that denatured
      Tat-SOD fusion protein is transduced into cells and skin tissue. Moreover, PEP-1
      peptide, which has 21 amino acid residues, is a known carrier peptide that
      delivers full-length native proteins in vitro and in vivo. In the present study,
      we investigated the protective effects of PEP-1-SOD fusion protein after ischemic
      insult. A human SOD gene was fused with PEP-1 peptide in a bacterial expression
      vector to produce a genetic in-frame PEP-1-SOD fusion protein. The expressed and
      purified fusion proteins were efficiently transduced both in vitro and in vivo
      with a native protein structure. Immunohistochemical analysis revealed that PEP-1
      SOD injected intraperitoneally (i.p.) into mice can have access into brain
      neurons. When i.p.-injected into gerbils, PEP-1-SOD fusion proteins prevented
      neuronal cell death in the hippocampus caused by transient forebrain ischemia.
      These results suggest that the biologically active intact forms of PEP-1-SOD
      provide a more efficient strategy for therapeutic delivery in various human
      diseases related to this antioxidant enzyme or to ROS, including stroke.

PMID- 15477019
TI  - Brain encoding and representation of 3D-space using different senses, in
      different species.

PMID- 15477020
TI  - Multiplication and stimulus invariance in a looming-sensitive neuron.
AB  - Multiplicative operations and invariance of neuronal responses are thought to
      play important roles in the processing of neural information in many sensory
      systems. Yet the biophysical mechanisms that underlie both multiplication and
      invariance of neuronal responses in vivo, either at the single cell or at the
      network level, remain to a large extent unknown. Recent work on an identified
      neuron in the locust visual system (the LGMD neuron) that responds well to
      objects looming on a collision course towards the animal suggests that this cell
      represents a good model to investigate the biophysical basis of multiplication
      and invariance at the single neuron level. Experimental and theoretical results
      are consistent with multiplication being implemented by subtraction of two
      logarithmic terms followed by exponentiation via active membrane conductances,
      according to a x 1/b = exp(log(a) - log(b)). Invariance appears to be in part due
      to non-linear integration of synaptic inputs within the dendritic tree of this
      neuron.

PMID- 15477021
TI  - From 1D to 2D via 3D: dynamics of surface motion segmentation for ocular tracking
      in primates.
AB  - In primates, tracking eye movements help vision by stabilising onto the retinas
      the images of a moving object of interest. This sensorimotor transformation
      involves several stages of motion processing, from the local measurement of one
      dimensional luminance changes up to the integration of first and higher-order
      local motion cues into a global two-dimensional motion immune to antagonistic
      motions arising from the surrounding. The dynamics of this surface motion
      segmentation is reflected into the various components of the tracking responses
      and its underlying neural mechanisms can be correlated with behaviour at both
      single-cell and population levels. I review a series of behavioural studies which
      demonstrate that the neural representation driving eye movements evolves over
      time from a fast vector average of the outputs of linear and non-linear spatio
      temporal filtering to a progressive and slower accurate solution for global
      motion. Because of the sensitivity of earliest ocular following to binocular
      disparity, antagonistic visual motion from surfaces located at different depths
      are filtered out. Thus, global motion integration is restricted within the depth
      plane of the object to be tracked. Similar dynamics were found at the level of
      monkey extra-striate areas MT and MST and I suggest that several parallel
      pathways along the motion stream are involved albeit with different latencies to
      build-up this accurate surface motion representation. After 200-300 ms, most of
      the computational problems of early motion processing (aperture problem, motion
      integration, motion segmentation) are solved and the eye velocity matches the
      global object velocity to maintain a clear and steady retinal image.

PMID- 15477022
TI  - 3-D-orientation with the octavolateralis system.
AB  - Fish detect and localize a sound source with inner ear receptors and with the
      mechanosensory lateral line. The inner ear of fish is sensitive to the water
      displacements caused by sound waves through a direct, inertial response by hair
      cell epithelia of the ear. Hearing specialists, such as goldfish and herring,
      have accessory peripheral structures that provide additional sensitivity to the
      pressure component of a sound wave. While the inner ear of fish responds to the
      whole body motions caused by sound waves and--in case of hearing specialists--to
      sound pressure, the lateral line is only sensitive to water motions relative to
      the surface of the fish and to local pressure gradients. Using lateral line
      and/or acoustic input, some fish can determine the direction and the distance to
      a sound source. Most likely they do so by exploiting some of the mechanisms
      described in this paper. Piscivorous fish may use lateral line input to detect
      the wakes caused by swimming fish. Even in the absence of light catfish, for
      instance, can follow a 10 s old, three-dimensional wake left by a prey fish over
      distances up to 55 prey-body length.

PMID- 15477023
TI  - Distance and shape: perception of the 3-dimensional world by weakly electric
      fish.
AB  - Weakly electric fish orient at night in complete darkness by employing their
      active electrolocation system. They emit short electric signals and perceive the
      consequences of these emissions with epidermal electroreceptors. Objects are
      detected by analyzing the electric images which they project onto the animal's
      electroreceptive skin surface. This process corresponds to similar processes
      during vision, where visual images are cast onto the retinas of eyes. Behavioral
      experiments have shown that electric fish can measure the distance of objects
      during active electrolocation, thus possessing three-dimensional depth perception
      of their surroundings. The fundamental mechanism for distance determination
      differs from stereopsis used during vision by two-eyed animals, but resembles
      some supplementary mechanisms for distance deduction in humans. Weakly electric
      fish can also perceive the three-dimensional shape of objects. The fish can learn
      to identify certain objects and discriminate them from all other objects. In
      addition, they spontaneously categorize objects according to their shapes and not
      according to object size or material properties. There is good evidence that some
      fundamental types of perceptional invariances during visual object recognition in
      humans are also found in electric fish during active electrolocation. These
      include size invariance (maybe including size constancy), rotational invariance,
      and translational invariance. The mechanisms of shape detection during
      electrolocation are still unknown, and their discoveries require additional
      experiments.

PMID- 15477024
TI  - Contributions of electric fish to the understanding of sensory processing by
      reafferent systems.
AB  - Sensory systems must solve the inverse problem of determining environmental
      events based on patterns of neural activity in the central nervous system that
      are affected by those environmental events. Different environmental events can
      give rise to indistinguishable patterns of neural activity, so that there will
      often, perhaps even always, be multiple solutions to a sensory inverse problem.
      Imaging strategies and brain organization confine these multiple solutions within
      a bounded set. Three different active strategies may be employed by animals to
      constrain the number of solutions to the sensory inverse problem: active
      generation of the energy (carrier) that stimulates receptors; reorientation of
      the point of view; and control of signal conditioning before transduction (pre
      receptor mechanisms). This paper describes how these strategies are used in
      sensory-motor systems, using electric fish as a paradigmatic example. Carrier
      generation and receptor tuning to the carrier improve signal to noise ratio.
      Receptor tuning to different frequency bands of the carrier spectrum allows a
      sensory system to evaluate different kinds of carrier modulations and to extract
      the different features of objects in the environment. Pre-receptor mechanisms
      condition the signals, optimizing their detection at a foveal region where the
      sensory resolution is maximum. Active orientation of the sensory surface
      redirects the fovea to explore in detail the source of interesting signals.
      Sensory input generated by these active exploration mechanisms ('reafference')
      has two components: one, necessary, derived from the self-generated actions and
      another, contingent, consisting of the information obtained from the external
      world. Extracting environmental information ('exafference') requires that the
      self generated afference be subtracted from the sensory inflow. Such subtraction
      is often associated with the generation and storage of expectations about sensory
      inputs. It can be concluded that an animal's perceptual world and its ability to
      transform the world are inextricably linked. Understanding sensory systems must,
      therefore, always require understanding the organization of motor behavior.

PMID- 15477025
TI  - Coding interaural time differences at low best frequencies in the barn owl.
AB  - In birds and mammals, precisely timed spikes encode the timing of acoustic
      stimuli, and interaural acoustic disparities propagate to binaural processing
      centers. The Jeffress model proposes that these projections act as delay lines to
      innervate an array of coincidence detectors, every element of which has a
      different relative delay between its ipsilateral and contralateral excitatory
      inputs. Thus, interaural time difference (ITD) is encoded into the position of
      the coincidence detector whose delay lines best cancel out the acoustic ITD.
      Neurons of the avian nucleus laminaris and mammalian MSO phase-lock to both
      monaural and binaural stimuli but respond maximally when phase-locked spikes from
      each side arrive simultaneously, i.e. when the difference in the conduction
      delays compensates for the ITD. McAlpine et al. [Nat. Neurosci. 4 (2001) 396]
      identified an apparent difference between avian and mammalian ITD coding. In the
      barn owl, the maximum firing rate appears to encode ITD. This may not be the case
      for the guinea pig, where the steepest region of the function relating discharge
      rate to interaural time delay (ITD) is close to midline for all neurons,
      irrespective of best frequency (BF). These data suggest that low BF ITD
      sensitivity in the guinea pig is mediated by detection of a change in slope of
      the ITD function, and not by maximum rate. We review coding of low best frequency
      ITDs in barn owls and mammals and discuss whether there may be differences in the
      code used to signal ITD in mammals and birds.

PMID- 15477026
TI  - Bi-sensory, striped representations: comparative insights from owl and platypus.
AB  - Bi-sensory striped arrays are described in owl and platypus that share some
      similarities with the other variant of bi-sensory striped array found in primate
      and carnivore striate cortex: ocular dominance columns. Like ocular dominance
      columns, the owl and platypus striped systems each involve two different
      topographic arrays that are cut into parallel stripes, and interdigitated, so
      that higher-order neurons can integrate across both arrays. Unlike ocular
      dominance stripes, which have a separate array for each eye, the striped array in
      the middle third of the owl tectum has a separate array for each cerebral
      hemisphere. Binocular neurons send outputs from both hemispheres to the striped
      array where they are segregated into parallel stripes according to hemisphere of
      origin. In platypus primary somatosensory cortex (S1), the two arrays of
      interdigitated stripes are derived from separate sensory systems in the bill,
      40,000 electroreceptors and 60,000 mechanoreceptors. The stripes in platypus S1
      cortex produce bimodal electrosensory-mechanosensory neurons with specificity for
      the time-of-arrival difference between the two systems. This "thunder-and
      lightning" system would allow the platypus to estimate the distance of the prey
      using time disparities generated at the bill between the earlier electrical wave
      and the later mechanical wave caused by the motion of benthic prey. The
      functional significance of parallel, striped arrays is not clear, even for the
      highly-studied ocular dominance system, but a general strategy is proposed here
      that is based on the detection of temporal disparities between the two arrays
      that can be used to estimate distance.

PMID- 15477027
TI  - Evidence for implication of primate area V1 in neural 3-D spatial localization
      processing.
AB  - We investigated the neural mechanisms underlying visual localization in 3-D space
      in area V1 of behaving monkeys. Three different sources of information, retinal
      disparity, viewing distance and gaze direction, that participate in these neural
      mechanisms are being reviewed. The way they interact with each other is studied
      by combining retinal and extraretinal signals. Interactions between retinal
      disparity and viewing distance have been shown in foveal V1; we have observed a
      strong modulation of the spontaneous activity and of the visual response of most
      V1 cells that was highly correlated with the vergence angle. As a consequence of
      these gain effects, neural horizontal disparity coding is favoured or refined for
      particular distances of fixation. Changing the gaze direction in the fronto
      parallel plane also produces strong gains in the visual response of half of the
      cells in foveal V1. Cells tested for horizontal disparity and orientation
      selectivities show gain effects that occur coherently for the same spatial
      coordinates of the eyes. Shifts in preferred disparity also occurred in several
      neurons. Cells tested in calcarine V1 at retinal eccentricities larger than 10
      degrees , show that horizontal disparity is encoded at least up to 20 degrees
      around both the horizontal and vertical meridians. At these large retinal
      eccentricities we found that vertical disparity is also encoded with tuning
      profiles similar to those of horizontal disparity coding. Combinations of
      horizontal and vertical disparity signals show that most cells encode both
      properties. In fact the expression of horizontal disparity coding depends on the
      vertical disparity signals that produce strong gain effects and frequent changes
      in peak selectivities. We conclude that the vertical disparity signal and the eye
      position signal serve to disambiguate the horizontal disparity signal to provide
      information on 3-D spatial coordinates in terms of distance, gaze direction and
      retinal eccentricity. We suggest that the relative weight among these different
      signals is the determining factor involved in the neural processing that gives
      information on 3-D spatial localization.

PMID- 15477028
TI  - A comparison of neural computations underlying stereo vision and sound
      localization.
AB  - Stereo vision and sound localization are behaviors that help organisms to orient
      in space. Stereo vision provides information about the distance of an object. In
      sound localization mainly directional signals are analyzed. Two specific cues,
      binocular disparities underlying stereo vision, and the interaural time
      difference, suited to represent azimuth in sound localization, have many
      computational problems in common, although they are generated in two different
      modalities. The extraction of both cues requires a comparison of signals that
      arise from two independent sensors, called two-sensor comparison here. This two
      sensor comparison is achieved by algorithms similar to summation, half-wave
      rectification and multiplication. Since the underlying neurons are band-pass
      filters, the two-sensor comparison results in ambiguities. These are removed in a
      hierarchical way in several computational steps, involving squaring, inhibition
      and across-frequency integration.

PMID- 15477029
TI  - Visual, haptic and cross-modal recognition of objects and scenes.
AB  - In this article we review current literature on cross-modal recognition and
      present new findings from our studies on object and scene recognition.
      Specifically, we address the questions of what is the nature of the
      representation underlying each sensory system that facilitates convergence across
      the senses and how perception is modified by the interaction of the senses. In
      the first set of our experiments, the recognition of unfamiliar objects within
      and across the visual and haptic modalities was investigated under conditions of
      changes in orientation (0 degrees or 180 degrees ). An orientation change
      increased recognition errors within each modality but this effect was reduced
      across modalities. Our results suggest that cross-modal object representations of
      objects are mediated by surface-dependent representations. In a second series of
      experiments, we investigated how spatial information is integrated across
      modalities and viewpoint using scenes of familiar, 3D objects as stimuli. We
      found that scene recognition performance was less efficient when there was either
      a change in modality, or in orientation, between learning and test. Furthermore,
      haptic learning was selectively disrupted by a verbal interpolation task. Our
      findings are discussed with reference to separate spatial encoding of visual and
      haptic scenes. We conclude by discussing a number of constraints under which
      cross-modal integration is optimal for object recognition. These constraints
      include the nature of the task, and the amount of spatial and temporal congruency
      of information across the modalities.

PMID- 15477030
TI  - Visuo-tactile representation of near-the-body space.
AB  - Here we report findings from neuropsychological investigations showing the
      existence, in humans, of intersensory integrative systems representing space
      through the multisensory coding of visual and tactile events. In addition, these
      findings show that visuo-tactile integration may take place in a privileged
      manner within a limited sector of space closely surrounding the body surface,
      i.e., the near-peripersonal space. They also demonstrate that the representation
      of near-peripersonal space is not static, as objects in the out-of-reach space
      can be processed as nearer, depending upon the (illusory) visual information
      about hand position in space, and the use of tools as physical extensions of the
      reachable space. Finally, new evidence is provided suggesting the multisensory
      coding of peripersonal space can be achieved through bottom-up processing that,
      at least in some instances, is not necessarily modulated by more "cognitive" top
      down processing, such as the expectation regarding the possibility of being
      touched. These findings are entirely consistent with the functional properties of
      multisensory neuronal structures coding near-peripersonal space in monkeys, as
      well as with behavioral, and neuroimaging evidence for the cross-modal coding of
      space in normal subjects. This high level of convergence ultimately favors the
      idea that multisensory space coding is achieved through similar multimodal
      structures in both humans and non-human primates.

PMID- 15477031
TI  - Multisensory contributions to the 3-D representation of visuotactile peripersonal
      space in humans: evidence from the crossmodal congruency task.
AB  - In order to determine precisely the location of a tactile stimulus presented to
      the hand it is necessary to know not only which part of the body has been
      stimulated, but also where that part of the body lies in space. This involves the
      multisensory integration of visual, tactile, proprioceptive, and even auditory
      cues regarding limb position. In recent years, researchers have become
      increasingly interested in the question of how these various sensory cues are
      weighted and integrated in order to enable people to localize tactile stimuli, as
      well as to give rise to the 'felt' position of our limbs, and ultimately the
      multisensory representation of 3-D peripersonal space. We highlight recent
      research on this topic using the crossmodal congruency task, in which
      participants make speeded elevation discrimination responses to vibrotactile
      targets presented to the thumb or index finger, while simultaneously trying to
      ignore irrelevant visual distractors presented from either the same (i.e.,
      congruent) or a different (i.e., incongruent) elevation. Crossmodal congruency
      effects (calculated as performance on incongruent-congruent trials) are greatest
      when visual and vibrotactile stimuli are presented from the same azimuthal
      location, thus providing an index of common position across different sensory
      modalities. The crossmodal congruency task has been used to investigate a number
      of questions related to the representation of space in both normal participants
      and brain-damaged patients. In this review, we detail the major findings from
      this research, and highlight areas of convergence with other cognitive
      neuroscience disciplines.

PMID- 15477032
TI  - Multisensory integration: methodological approaches and emerging principles in
      the human brain.
AB  - Understanding the conditions under which the brain integrates the different
      sensory streams and the mechanisms supporting this phenomenon is now a question
      at the forefront of neuroscience. In this paper, we discuss the opportunities for
      investigating these multisensory processes using modern imaging techniques, the
      nature of the information obtainable from each method and their benefits and
      limitations. Despite considerable variability in terms of paradigm design and
      analysis, some consistent findings are beginning to emerge. The detection of
      brain activity in human neuroimaging studies that resembles multisensory
      integration responses at the cellular level in other species, suggests similar
      crossmodal binding mechanisms may be operational in the human brain. These
      mechanisms appear to be distributed across distinct neuronal networks that vary
      depending on the nature of the shared information between different sensory cues.
      For example, differing extents of correspondence in time, space or content seem
      to reliably bias the involvement of different integrative networks which code for
      these cues. A combination of data obtained from haemodynamic and electromagnetic
      methods, which offer high spatial or temporal resolution respectively, are
      providing converging evidence of multisensory interactions at both "early" and
      "late" stages of processing--suggesting a cascade of synergistic processes
      operating in parallel at different levels of the cortex.

PMID- 15477033
TI  - Adaptation to left-right reversed vision rapidly activates ipsilateral visual
      cortex in humans.
AB  - The brain mechanisms of adaptation to visual transposition are of increasing
      interest, not only for research on sensory-motor coordination, but also for
      neuropsychological rehabilitation. Sugita [Nature 380 (1996) 523] found that
      after adaptation to left-right reversed vision for one and a half months, monkey
      V1 neurons responded to stimuli presented not only in the contralateral visual
      field, but also in the ipsilateral visual field. To identify the underlying
      neuronal mechanisms of adaptation to visual transposition, we conducted fMRI and
      behavioral experiments for which four adult human subjects wore left-right
      reversing goggles for 35/39 days, and investigated: (1) whether ipsilateral V1
      activation can be induced in human adult subjects; (2) if yes, when the
      ipsilateral activity starts, and what kind of behavioral/psychological changes
      occur accompanying the ipsilateral activity; (3) whether other visual cortices
      also show an ipsilateral activity change. The results of behavioral experiments
      showed that visuomotor coordinative function and internal representation of
      peripersonal space rapidly adapted to the left-right reversed vision within the
      first or second week. Accompanying these behavioral changes, we found that both
      primary (V1) and extrastriate (MT/MST) visual cortex in human adults responded to
      visual stimuli presented in the ipsilateral visual field. In addition, the
      ipsilateral activity started much sooner than the one and a half months, which
      had been expected from the monkey neurophysiological study. The results of the
      present study serve as physiological evidence of large-scale, cross-hemisphere,
      cerebral plasticity that exists even in adult human brain.

PMID- 15477034
TI  - Behavioral and neuroplastic changes in the blind: evidence for functionally
      relevant cross-modal interactions.
AB  - The study of blind individuals provides insight into the brain re-organization
      and behavioral compensations that occur following sensory deprivation. While
      behavioral studies have yielded conflicting results in terms of performance
      levels within the remaining senses, deafferentation of visual cortical areas
      through peripheral blindness results in clear neuroplastic changes. Most striking
      is the activation of occipital cortex in response to auditory and tactile
      stimulation. Indeed, parts of the "unimodal" visual cortex are recruited by other
      sensory modalities to process sensory information in a functionally relevant
      manner. In addition, a larger area of the sensorimotor cortex is devoted to the
      representation of the reading finger in blind Braille readers. The "visual"
      function of the deafferented occipital cortex is also altered, where transcranial
      magnetic stimulation-induced phosphenes can be elicited in only 20% of blind
      subjects. The neural mechanisms underlying these changes remain elusive but
      recent data showing rapid cross-modal plasticity in blindfolded, sighted subjects
      argue against the establishment of new connections to explain cross-modal
      interactions in the blind. Rather, latent pathways that participate in
      multisensory percepts in sighted subjects might be unmasked and may be
      potentiated in the event of complete loss of visual input. These issues have
      important implications for the development of visual prosthesis aimed at
      restoring some degree of vision in the blind.

PMID- 15477035
TI  - Ocular tracking as a measure of auditory motion perception.
AB  - Motion is a potent sub-modality of vision. Motion cues alone can be used to
      segment images into figure and ground and break camouflage. Specific patterns of
      motion support vivid percepts of form, guide locomotion by specifying directional
      heading and the passage of objects, and in case of an impending collision, the
      time to impact. Visual motion also drives smooth pursuit eye movements (SPEMs)
      that serve to stabilize the retinal image of objects in motion. In contrast, the
      auditory system does not appear to be particularly sensitive to motion. We review
      the ambiguous status of auditory motion processing from the psychophysical and
      electrophysiological perspectives. We then report the results of two experiments
      that use ocular tracking performance as an objective measure of the perception of
      auditory motion in humans. We examine ocular tracking of auditory motion, visual
      motion, combined auditory + visual motion and imagined motion in both the frontal
      plane and in depth. The results demonstrate that ocular tracking of auditory
      motion is no better than ocular tracking of imagined motion. These results are
      consistent with the suggestion that, unlike the visual system, the human auditory
      system is not endowed with low-level motion sensitive elements. We hypothesize
      however, that auditory information may gain access to a recently described high
      level motion processing system that is heavily dependent on 'top-down'
      influences, including attention.

PMID- 15477036
TI  - Bayesian multisensory integration and cross-modal spatial links.
AB  - Our perception of the word is the result of combining information between several
      senses, such as vision, audition and proprioception. These sensory modalities use
      widely different frames of reference to represent the properties and locations of
      object. Moreover, multisensory cues come with different degrees of reliability,
      and the reliability of a given cue can change in different contexts. The Bayesian
      framework--which we describe in this review--provides an optimal solution to deal
      with this issue of combining cues that are not equally reliable. However, this
      approach does not address the issue of frames of references. We show that this
      problem can be solved by creating cross-modal spatial links in basis function
      networks. Finally, we show how the basis function approach can be combined with
      the Bayesian framework to yield networks that can perform optimal multisensory
      combination. On the basis of this theory, we argue that multisensory integration
      is a dialogue between sensory modalities rather that the convergence of all
      sensory information onto a supra-modal area.

PMID- 15477037
TI  - How do insects represent familiar terrain?
AB  - We argue here that ants and bees have a piecemeal representation of familiar
      terrain. These insects remember no more than what is needed to sustain the
      separate and parallel strategies that they employ when travelling between their
      nest and foraging sites. One major strategy is path integration. The insect keeps
      a running tally of its distance and direction from the nest and so can always
      return home. This global path integration is enhanced by long-term memories of
      significant sites that insects store in terms of the coordinates (direction and
      distance) of these sites relative to the nest. With these memories insects can
      plan routes that are steered by path integration to such sites. Quite distinct
      from global path integration are memories associated with familiar routes. Route
      memories include stored views of landmarks along the route with, in some cases,
      local vectors linked to them. Local vectors by encoding the direction and/or
      distance from one landmark to the next, or from one landmark to a goal, help an
      insect keep to a defined route. We review experiments showing that although local
      vectors can be recalled by recognising landmarks, the global path integration
      system is independent of landmark information and that landmarks do not have
      positional coordinates associated with them. The major function of route
      landmarks is thus procedural, telling an insect what action to perform next,
      rather than its location relative to the nest.

PMID- 15477038
TI  - Crossmodal integration for perception and action.
AB  - The integration of information from different sensory modalities has many
      advantages for human observers, including increase of salience, resolution of
      perceptual ambiguities, and unified perception of objects and surroundings.
      Several behavioral, electrophysiological and neuroimaging data collected in
      various tasks, including localization and detection of spatial events, crossmodal
      perception of object properties and scene analysis are reviewed here. All the
      results highlight the multiple faces of crossmodal interactions and provide
      converging evidence that the brain takes advantages of spatial and temporal
      coincidence between spatial events in the crossmodal binding of spatial features
      gathered through different modalities. Furthermore, the elaboration of a
      multimodal percept appears to be based on an adaptive combination of the
      contribution of each modality, according to the intrinsic reliability of sensory
      cue, which itself depends on the task at hand and the kind of perceptual cues
      involved in sensory processing. Computational models based on bayesian sensory
      estimation provide valuable explanations of the way perceptual system could
      perform such crossmodal integration. Recent anatomical evidence suggest that
      crossmodal interactions affect early stages of sensory processing, and could be
      mediated through a dynamic recurrent network involving backprojections from
      multimodal areas as well as lateral connections that can modulate the activity of
      primary sensory cortices, though future behavioral and neurophysiological studies
      should allow a better understanding of the underlying mechanisms.

PMID- 15477039
TI  - Visual guidance based on optic flow: a biorobotic approach.
AB  - This paper addresses some basic questions as to how vision links up with action
      and serves to guide locomotion in both biological and artificial creatures. The
      thorough knowledge gained during the past five decades on insects' sensory-motor
      abilities and the neuronal substrates involved has provided us with a rich source
      of inspiration for designing tomorrow's self-guided vehicles and micro-vehicles,
      which will be able to cope with unforeseen events on the ground, under water, in
      the air, in space, on other planets, and inside the human body. Insects can teach
      us some useful tricks for designing agile autonomous robots. Since constructing a
      "biorobot" first requires exactly formulating the biological principles
      presumably involved, it gives us a unique opportunity of checking the soundness
      and robustness of these principles by bringing them face to face with the real
      physical world. "Biorobotics" therefore goes one step beyond computer simulation.
      It leads to experimenting with real physical robots which have to pass the
      stringent test of the real world. Biorobotics provide us with a new tool, which
      can help neurobiologists and neuroethologists to identify and investigate
      worthwhile issues in the field of sensory-motor control. Here we describe some of
      the visually guided terrestrial and aerial robots we have developed since 1985 on
      the basis of our biological findings. All these robots behave in response to the
      optic flow, i.e., they work by measuring the slip speed of the retinal image.
      Optic flow is sensed on-board by miniature electro-optical velocity sensors. The
      very principle of these sensors was based on studies in which we recorded the
      responses of single identified neurons to single photoreceptor stimulation in a
      model visual system: the fly's compound eye.

PMID- 15477040
TI  - Current concepts on Escherichia coli K1 translocation of the blood-brain barrier.
AB  - The mortality and morbidity associated with neonatal gram-negative meningitis
      have remained significant despite advances in antimicrobial chemotherapy.
      Escherichia coli K1 is the most common gram-negative organism causing neonatal
      meningitis. Our incomplete knowledge of the pathogenesis of this disease is one
      of the main reasons for this high mortality and morbidity. We have previously
      established both in vitro and in vivo models of the blood-brain barrier (BBB)
      using human brain microvascular endothelial cells (HBMEC) and hematogenous
      meningitis in neonatal rats, respectively. With these in vitro and in vivo
      models, we have shown that successful crossing of the BBB by circulating E. coli
      requires a high-degree of bacteremia, E. coli binding to and invasion of HBMEC,
      and E. coli traversal of the BBB as live bacteria. Our previous studies using
      TnphoA, signature-tagged mutagenesis and differential fluorescence induction
      identified several E. coli K1 determinants such as OmpA, Ibe proteins, AslA, TraJ
      and CNF1 contributing to invasion of HBMEC in vitro and traversal of the blood
      brain barrier in vivo. We have shown that some of these determinants interact
      with specific receptors on HBMEC, suggesting E. coli translocation of the BBB is
      the result of specific pathogen-host cell interactions. Recent studies using
      functional genomics techniques have identified additional E. coli K1 factors that
      contribute to the high degree of bacteremia and HBMEC
      binding/invasion/transcytosis. In this review, we summarize the current knowledge
      on the mechanisms underlying the successful E. coli translocation of the BBB.

PMID- 15477041
TI  - Impact of drug resistance on fitness of Mycobacterium tuberculosis strains of the
      W-Beijing genotype.
AB  - Mycobacterium tuberculosis strains of the W-Beijing genotype became a common
      cause of tuberculosis during the past years and they are often associated with
      drug resistance. The biological factors facilitating the selection and wide
      dissemination of these strains are not known. To determine how acquisition of
      drug resistance affected growth of strains of the W-Beijing genotype, the growth
      of 55 M. tuberculosis isolates were studied using the BBL MGIT Mycobacteria
      Growth Indicator Tube and the BACTEC MGIT 960 System. Susceptible strains of non
      Beijing genotypes were found to be the most fit strains. Drug-resistant strains
      of non-Beijing genotypes were more likely to grow slower than susceptible strains
      (P=0.001). Drug-resistant strains of the W-Beijing genotype had two tendencies of
      growth: some of them showed reduced growth compared to susceptible strains, while
      others did not show loss of fitness measured as growth.

PMID- 15477042
TI  - A growth study of Coxiella burnetii Nine Mile Phase I and Phase II in
      fibroblasts.
AB  - Coxiella burnetii, a slow-growing, gram-negative, obligate intracellular
      bacterium, is the causative agent of Q fever in humans. The avirulent Phase II C.
      burnetii Nine Mile strain can invade and establish persistent infections in a
      wide variety of laboratory cell lines, and is generally considered to be easier
      to grow in culture than the wild-type Phase I organism. Efforts to improve Phase
      I organism yield in the BHK-21 cell line demonstrated that high CO2 conditions
      and the use of Dulbecco's modified Eagle's medium (DMEM) with 4.5 g/l glucose
      supplementation resulted in higher organism yields. Phase II organisms grown in
      the same cell line and conditions showed lower growth rates. Analysis revealed
      that increased average numbers of C. burnetii Phase I organisms within
      fibroblasts was due to higher growth rates within the hosts rather than to
      increased uptake or to increased cell-to-cell spreading. Addition of the
      nucleoside cytidine to the growth medium stimulated growth of Phase II but not
      Phase I organisms.

PMID- 15477043
TI  - Interferon-gamma deficiency reveals that 129Sv mice are inherently more
      susceptible to Anaplasma phagocytophilum than C57BL/6 mice.
AB  - Immunocompetent mice 129Sv (129) and C57BL/6 (B6) mice are similarly susceptible
      to Anaplasma phagocytophilum. We now show that 129 mice lacking interferon-gamma
      (IFN-gamma) develop more severe infection with A. phagocytophilum than IFN-gamma
      deficient B6 mice. These data demonstrate that there is an inherent increased
      susceptibility of 129 mice, compared with B6 mice, to A. phagocytophilum that can
      only be discerned in the absence of IFN-gamma.

PMID- 15477044
TI  - Detection of Helicobacter pylori in bile of cats.
AB  - Lymphocytic cholangitis (LC) in cats is a biliary disease of unknown etiology.
      Helicobacter spp. were recently implicated in human primary sclerosing
      cholangitis (PSC) and primary biliary cirrhosis (PBC). Because of the
      similarities between PSC/PBC with LC, we hypothesized that Helicobacter spp. are
      involved in feline LC. A PCR with Helicobacter genus-specific 16S rRNA primers
      was performed on DNA isolated from feline bile samples. Four of the 15 (26%) LC
      samples were positive, whereas only 8/51 (16%) of non-LC samples were PCR
      positive (p=0.44). Sequence analysis of the amplicons revealed a 100% identity
      with the Helicobacter pylori specific DNA fragments. Our data suggest an
      etiological role of H. pylori in feline LC and that cats are a potential zoonotic
      reservoir.

PMID- 15477045
TI  - Clofibric and ethacrynic acids prevent experimental pyelonephritis by Escherichia
      coli in mice.
AB  - Interfering Escherichia coli attachment to the urinary tract, using P-fimbriation
      inhibitors, can prevent pyelonephritis. Clofibric and ethacrynic acids are
      organic compounds structurally related, but with different pharmacological uses.
      These agents are potentially active in the urinary tract due to its elimination
      in an unaltered form by the renal route. This study described a
      pyelonephritogenic E. coli strain, grown in the presence of sub-inhibitory
      concentrations of clofibric or ethacrynic acids (0.1 and 1 mM, respectively),
      which exhibits inhibition of P1 erythrocytes agglutination and a drastic decrease
      in fimbriation, using electron microscopy and quantitative analyses of
      superficial proteins (decrease to a 17-25% in comparison with the control). In
      vivo assays were performed using ascending urinary tract infection in mice. The
      treatment with therapeutic doses of the drugs, administered 2 days before the
      bacterial challenge and daily until the end of the experiment (22 days),
      abolished renal infection after 7-10 days of drug exposure. Within this period
      clofibric acid did not produce adverse effects on the renal parenchyma. However,
      ethacrynic acid caused pyelitis and tubular cellular desquamation. These results
      suggested that clofibric acid might be useful in the short-term prophylaxis of
      urinary tract infection.

PMID- 15477046
TI  - Migration and maturation of human dendritic cells infected with Toxoplasma gondii
      depend on parasite strain type.
AB  - Migration and maturation of human dendritic cells derived from CD34+ progenitor
      cells (DC) infected by Toxoplasma gondii were studied in an in vitro model. We
      demonstrated that infection with virulent type I strains RH and ENT or type II
      low virulent strains PRU and CAL induced DC migration towards MIP-3beta. However,
      type II strains induced a higher percentage of migrating cells than that induced
      by type I strains or positive controls (chemical allergen or
      lipopolysaccharides). Type II strains produced soluble factors responsible of the
      high migration whereas heat killed tachyzoites did not induced a migration higher
      than positive controls. We also demonstrated that infection by virulent strains
      and not by type II stains or heat killed tachyzoites triggers DC maturation. A
      soluble factor released by type II strains was responsible of the absence of DC
      maturation. Taken together, these results demonstrated that the interference of
      T. gondii in the behaviour of DC functions is related to the strain types and can
      be supported by secretion of soluble factors by the parasite.

PMID- 15477047
TI  - Smartening up our act.

PMID- 15477048
TI  - Compliance with the CONSORT checklist in obstetric anaesthesia randomised
      controlled trials.
AB  - The Consolidated Standards for Reporting of Trials (CONSORT) checklist is an
      evidence-based approach to help improve the quality of reporting randomised
      controlled trials. The purpose of this study was to determine how closely
      randomised controlled trials in obstetric anaesthesia adhere to the CONSORT
      checklist. We retrieved all randomised controlled trials pertaining to the
      practice of obstetric anaesthesia and summarised in Obstetric Anesthesia Digest
      between March 2001 and December 2002 and compared the quality of reporting to the
      CONSORT checklist. The median number of correctly described CONSORT items was 65%
      (range 36% to 100%). Information pertaining to randomisation, blinding of the
      assessors, sample size calculation, reliability of measurements and reporting of
      the analysis were often omitted. It is difficult to determine the value and
      quality of many obstetric anaesthesia clinical trials because journal editors do
      not insist that this important information is made available to readers. Both
      clinicians and clinical researchers would benefit from uniform reporting of
      randomised trials in a manner that allows rapid data retrieval and easy
      assessment for relevance and quality.

PMID- 15477049
TI  - Effect of varying doses of fentanyl with low dose spinal bupivacaine for
      caesarean delivery in patients with pregnancy-induced hypertension.
AB  - The purpose of this study was to evaluate haemodynamic stability, perioperative
      analgesia and neonatal outcome following intrathecal 0.5% bupivacaine 7.5 mg with
      varying doses of fentanyl, in parturients with pregnancy-induced hypertension.
      Forty-five parturients with pregnancy-induced hypertension scheduled for
      caesarean section were randomly allocated to receive 7.5 mg bupivacaine with
      saline 1 mL (group B), fentanyl 10 microg (group Bf10) or fentanyl 20 microg
      (group Bf20) intrathecally. Heart rate, blood pressure, and sensory block were
      recorded at regular intervals. Pain, nausea, vomiting, pruritus or any other side
      effects were sought. Neonatal outcome was assessed using Apgar score and
      umbilical artery blood gas analysis. Adequate surgical anaesthesia was
      established in all three groups. There was a statistically significant fall in
      mean arterial pressure in all three groups within 4-6 min of subarachnoid block
      (P<0.05), but the decrease in MAP was <20% of baseline in all three groups. Pain
      and discomfort during surgery were experienced more frequently in group B than in
      groups Bf10 and Bf20 (P<0.05). Duration of postoperative analgesia was
      significantly longer in group Bf20 (5.55+/-1.18 h) than in group Bf10 (3.97+/
      2.12 h) and group B (3.27+/-1.8 h) (P<0.05). Neonatal outcome was similar in the
      three groups. Intrathecal fentanyl with low dose bupivacaine provides good
      surgical anaesthesia and prolongs the duration of analgesia without haemodynamic
      or neonatal compromise in patients with pregnancy-induced hypertension undergoing
      caesarean delivery.

PMID- 15477050
TI  - General anesthesia for cesarean section in a Singapore maternity hospital: a
      retrospective survey.
AB  - We conducted a retrospective study of all cases of cesarean section at the KK
      Women's and Children's Hospital over a one-year period from September 1, 2002 to
      August 31, 2003, with the aim of evaluating current anesthetic practice. These
      cases were identified using hospital databases and relevant data was extracted
      from clinical notes. There were 14244 deliveries during the study period with a
      cesarean section rate of 25.2% (3583 cases). Of these, 20.4% (732 cases) were
      performed under general anesthesia. Maternal request was the chief reason for
      general anesthesia, especially among elective cases. Regional block failure
      accounted for 16% of the general anesthesia cases performed or 4.0% of the total
      regional techniques attempted. Regional block failure rate was highest for
      emergency cases in which an indwelling labor epidural catheter was used to
      provide surgical anesthesia via a bolus top-up. General anesthesia still has a
      definite place for cesarean delivery despite the predominant use of regional
      techniques in our institution.

PMID- 15477051
TI  - Incidence and characteristics of failures in obstetric neuraxial analgesia and
      anesthesia: a retrospective analysis of 19,259 deliveries.
AB  - A retrospective analysis was performed on 19,259 deliveries that occurred in our
      institution from January 2000 to December 2002. Anesthesia records and quality
      assurance data sheets were reviewed for the characteristics and failure rates of
      neuraxial blocks performed for labor analgesia and anesthesia. The neuraxial
      labor analgesia rate was 75% and the overall failure rate was 12%. After adequate
      analgesia from initial placement, 6.8% of patients had subsequent inadequate
      analgesia during labor that required epidural catheter replacement. Ultimately
      98.8% of all patients received adequate analgesia even though 1.5% of patients
      had multiple replacements. Six percent of epidural catheters had initial
      intravenous placement but 46% were made functional by simple manipulations
      without higher subsequent failure. Unintended dural puncture occurred in 1.2% of
      labor neuraxial analgesia. The incidences of overall failure, intravenous
      epidural catheter, wet tap, inadequate epidural analgesia and catheter
      replacement were lower in patients receiving combined spinal-epidural versus
      epidural analgesia. For cesarean section, 7.1% of pre-existing labor epidural
      catheters failed and 4.3% of patients required conversion to general anesthesia.
      Spinal anesthesia for cesarean section had a lower failure rate of 2.7%, with
      1.2% of the patients requiring general anesthesia. The overall use of general
      anesthesia decreased from 8% to 4.3% over the three-year period. Furthermore,
      regional anesthesia was used in 93.5% of cesarean deliveries with no anesthetic
      related mortalities. Future investigations should identify acceptable
      international standards, risk factors associated with failure and methods to
      reduce failure before cesarean section.

PMID- 15477052
TI  - Interactive effect of sevoflurane with isradipine or indomethacin on spontaneous
      contractile activity of isolated pregnant rat myometrium.
AB  - Volatile anesthetics, calcium antagonists and non-steroidal anti-inflammatory
      drugs inhibit contractile activity of myometrial smooth muscle. The aim of this
      study was to investigate the interactive effect of sevoflurane with isradipine or
      indomethacin on spontaneous contractile activity of myometrial strips isolated
      from pregnant rats. The myometrial strips were excised from rats (250-300 g) at
      19-21 days of gestation and mounted in tissue baths for recording of isometric
      tension. Sevoflurane (0.5 to 3 MAC) inhibited the amplitude and frequency of
      spontaneous myometrial contractions in a concentration-dependent manner (P<0.05).
      Sevoflurane responses were repeated in the presence of isradipine (a
      dihydropyridine-type calcium channel blocker) and indomethacin (a non-selective
      cyclooxygenase (COX) inhibitor). Pretreatment with isradipine (10(-6) M) or
      indomethacin (10(-7) M), concentrations that themselves had no effect on
      spontaneous contractility, significantly increased the inhibitor responses to
      sevoflurane on amplitude and frequency of myometrial contractions, beginning at 1
      MAC (P<0.05). Blockade of calcium channels in myometrial smooth muscle may
      increase the inhibitor effect of sevoflurane. Further work is needed to determine
      the cellular mechanism(s) of this interaction.

PMID- 15477053
TI  - Spinal anesthesia for cesarean section following inadequate labor epidural
      analgesia: a retrospective audit.
AB  - BACKGROUND: High blocks have been reported when spinal anesthesia is used for
      cesarean section following inadequate labor epidural analgesia. We have therefore
      modified the practice at our institution to minimize this risk and conducted a
      retrospective observational study of outcome following the change of practice.
      METHOD: The records of 115 women with inadequate epidural labor analgesia who
      required cesarean section between July 1998 and January 2002 were studied. No
      epidural boluses were administered in the 30 min preceding spinal anesthesia and
      a reduced spinal dose, median (range) 9.38 mg (7.5-11.3 mg) of 0.75% hyperbaric
      bupivacaine and fentanyl 15 microg (10-25 microg) was used. Patients were left
      sitting for 2 min and then positioned supine with left uterine displacement and
      were closely monitored for symptoms or signs that would suggest a high block.
      RESULTS: No parturient developed a high spinal necessitating intubation, and
      there was no adverse neonatal outcome. CONCLUSION: These findings do not
      conclusively establish this method as safe, but should spinal anesthesia for
      cesarean section following suboptimal labor epidural analgesia be considered,
      avoiding epidural boluses immediately preceding spinal injection, using a lower
      spinal dose, and delayed supine positioning following spinal injection may be
      advisable.

PMID- 15477054
TI  - Anesthesia for obstetric patients with Gaucher disease: survey and review.
AB  - Pregnancy and delivery in patients with non-neuronopathic Gaucher disease,
      whether treated with enzyme replacement or untreated, are usually uncomplicated.
      Various factors may influence mode of delivery, vaginal or cesarean section, as
      well as type of anesthesia, general or regional, used during delivery. This
      retrospective review was intended to highlight some of the practical issues
      relating to obstetric anesthetic management, based on a review of the literature
      and experiences from a large referral clinic for Gaucher disease. In the past
      decade, there were 16 deliveries in 11 women in our institution. There were five
      normal vaginal deliveries, two vacuum extractions, one placental extraction, and
      eight cesarean sections. Platelet counts were 27-215 x 10(9)/L. Two spontaneous
      deliveries and one vacuum extraction were performed under epidural anesthesia;
      two other women having vaginal deliveries and one vacuum extraction were given
      i.v. analgesia; the fifth was given i.v. patient-controlled analgesia. The
      placental extraction was performed under general anesthesia. Seven of the women
      having cesarean deliveries received spinal anesthesia; the breech presentation
      required general anesthesia. There were no anesthesia-related side effects or
      complications, although there were some instances of post-partum bleeding
      irrespective of enzyme therapy. Gaucher disease affects multiple organs and can
      be a challenge to the anesthesiologist. Based on this survey we suggest that
      anesthetic management requires particular attention to hematological parameters
      before delivery. A multidisciplinary approach and extensive communication among
      obstetrician, hematologist and anesthesiologist is required to anticipate the
      possibility of post-partum hemorrhage, and preclude skeletal damage.

PMID- 15477055
TI  - Partners should be allowed to stay in the operating theatre during caesarean
      section under general anaesthesia.

PMID- 15477056
TI  - Partners should be allowed to stay in the operating theatre during caesarean
      section under general anaesthesia.

PMID- 15477057
TI  - Epidural top-ups for category I/II emergency caesarean section should be given
      only in the operating theatre.

PMID- 15477058
TI  - Epidural top-ups for category I/II emergency caesarean section should be given
      only in the operating theatre.

PMID- 15477059
TI  - Anaesthetic management of aortic coarctation in pregnancy.
AB  - We report two cases of aortic coarctation in pregnancy. The first was a 20-year
      old nulliparous woman who underwent an aortic coarctation repair when she was 23
      weeks old and subsequently developed an aneurysm at the site of initial repair.
      The second was a 20-year-old nulliparous woman with a severe uncorrected
      congenital aortic coarctation and upper body hypertension, who became pregnant
      whilst awaiting transcatheter dilatation of the coarctation. Antenatal care
      involved a multidisciplinary approach with obstetric, anaesthetic and cardiology
      input. Both parturients were delivered by elective caesarean section. A cautious,
      incremental regional anaesthetic technique was used, with no associated maternal
      or neonatal morbidity. Perioperative management focused on minimising
      haemodynamic disturbances. The management is discussed, together with the
      potential maternal and fetal complications of aortic coarctation in pregnancy.

PMID- 15477060
TI  - Amniotic fluid embolism during caesarean section.
AB  - Amniotic fluid embolism occurs rarely but is a leading cause of maternal
      mortality. A high index of clinical suspicion is necessary to make an early
      diagnosis to reduce morbidity and mortality. We report a non-fatal case of
      amniotic fluid embolism occurring during a caesarean section, with special
      emphasis on the mode of development and diagnosis. The initial presentation of
      this syndrome was a coagulopathy, followed by the usual complications of massive
      bleeding. Although non-specific, the diagnosis of amniotic fluid embolism was
      supported by the observation of amniotic fluid in the central venous blood as
      well as in the broncho-alveolar fluid.

PMID- 15477061
TI  - Autoimmune progesterone dermatitis in a parturient for emergency caesarean
      section.
AB  - A parturient with a 14-year history of autoimmune progesterone dermatitis
      presented in labour at 36 weeks' gestation. She had suffered recurrent episodes
      of angioedema over a long period and had been scheduled for elective caesarean
      hysterectomy and bilateral oophorectomy at 37 weeks' gestation. In most cases
      surgical oophorectomy provides prolonged relief from the recurrent angioedema and
      dermatological manifestations that are typical of autoimmune progesterone
      dermatitis. Spinal anaesthesia was chosen in order to avoid airway manipulation,
      a factor frequently implicated in the development of angioedema. Delivery was
      uneventful and the obstetricians proceeded to hysterectomy and oophorectomy.
      Forty minutes after delivery the patient experienced an attack of angioedema, she
      was markedly hypotensive and was given fluids, ephedrine and phenylephrine with
      good effect. As she remained normotensive, she was given intramuscular rather
      than intravenous epinephrine to provide a slower release. She recovered well and
      stabilised without the need for intubation or ventilation. This case reinforces
      the rationale for regional anaesthesia in these patients and demonstrates how
      intramuscular epinephrine contributed towards a positive outcome.

PMID- 15477062
TI  - Massive amniotic fluid embolism: diagnosis aided by emergency transesophageal
      echocardiography.
AB  - A 36-year-old woman was hospitalized at term and in labor at 3-cm cervical
      dilatation. The early labor course was remarkable only for oxytocin augmentation
      and combined spinal-epidural analgesia. Eight hours after admission, tetanic
      uterine contractions ensued, followed by persistent fetal bradycardia. An
      emergency cesarean section was performed and a viable male infant was delivered.
      Intraoperatively, a placental abruption was identified, and disseminated
      intravascular coagulation and persistent hypotension developed despite
      resuscitative efforts. Transesophageal echocardiography revealed normal left
      ventricular contractility and gross enlargement of the right ventricle and main
      pulmonary trunk, consistent with acute right ventricular pressure overload and
      underloading of the left ventricle. Despite resuscitative efforts, the patient
      died three hours postoperatively. Autopsy showed extensive microvascular plugging
      of the pulmonary capillaries by fetal cells in all lung fields. This is a rare
      case of amniotic fluid embolism diagnosed in part and managed pre-mortem with
      transesophageal echocardiography and confirmed by autopsy findings.

PMID- 15477063
TI  - Diaphragmatic rupture during labor.
AB  - Diaphragmatic rupture during labor is uncommon and generally occurs in patients
      with a history of congenital diaphragmatic hernia or traumatic abdominal or chest
      injury. We present a case of a 41-year-old woman who presented with abdominal
      pain, vomiting and hypoventilation four days after a full-term home delivery.
      Chest radiography suggested the presence of a ruptured diaphragm, and laparotomy
      revealed a congenital left Bochdalek defect with herniation of the stomach,
      transverse colon and spleen into the left pleural cavity. Diaphragmatic hernia
      rupture during labor is a serious but rare complication that requires emergency
      surgery to prevent visceral perforation and cardio-respiratory failure.

PMID- 15477064
TI  - Maternal cardiac arrest associated with attempted fetal injection of potassium
      chloride.
AB  - We report a case of maternal cardiac arrest immediately after attempted fetal
      cardiac injection of potassium chloride. Prompt institution of maternal cardiac
      life-support protocols resulted in successful maternal resuscitation. The
      management of this case as well as that of fetal cardiac injections of potassium
      chloride is reviewed.

PMID- 15477065
TI  - Transient cortical blindness after caesarean hysterectomy for placenta percreta.

PMID- 15477066
TI  - Prophylactic epidural blood patch (PEBP) in obstetrics: yes or no?

PMID- 15477068
TI  - A high spinal or a subdural block?

PMID- 15477069
TI  - Anaesthetic management of labour in a woman with quadriplegia and autonomic
      hyperreflexia.

PMID- 15477070
TI  - Caudal labor analgesia following lumbar epidural catheter placement.

PMID- 15477071
TI  - Spontaneous cervical epidural hematoma during pregnancy: management concerns.

PMID- 15477072
TI  - Another cause of distortion of the spinal needle.

PMID- 15477074
TI  - Standard dose hyperbaric bupivacaine is safe and effective for CSE in morbidly
      obese patients.

PMID- 15477075
TI  - General co-expression vectors for the overexpression of heterodimeric protein
      complexes in Escherichia coli.
AB  - We have designed and constructed a novel pair of bacterial co-expression vectors
      to facilitate the production of substantial amounts of recombinant multiprotein
      complexes for biochemical, biophysical, and structural studies. pOKD4 (kanamycin
      resistant) and pOKD5 (ampicillin-resistant) are derivatives of pACYC177 cloning
      and pET26b expression vectors. As a result, pOKD4 and pOKD5 are T7-based
      expression plasmids containing the p15A origin of replication. This feature
      permits either pOKD4 or pOKD5 to co-exist in the same bacterial cell with most
      Escherichia coli expression vectors including the popular pET expression vectors.
      The pOKD4 and pOKD5 vectors have been engineered to possess exactly the same
      multiple cloning sites as pET26b thus allowing for the relatively easy shuttling
      of genes to and fro. The efficacy and versatility of this novel pair of co
      expression vectors was successfully applied to the production of significant
      amounts of active DFF40/DFF45 heterodimeric protein complex in E. coli for
      detailed biochemical and structural studies.

PMID- 15477076
TI  - Overexpression in Escherichia coli and purification of recombinant CI-b1, a
      Kunitz-type chymotrypsin inhibitor of silkworm.
AB  - Present research provided an efficient approach to obtain large quantities of
      active recombinant CI-b1, a Kunitz-type chymotrypsin inhibitor of silkworm,
      Bombyx mori. The cDNA encoding mature CI-b1 was cloned into pDEST17 vector.
      Recombinant protein with hexa-histidine tag attached to the N-terminal of CI-b1
      was expressed in Escherichia coli Origami B cells. It can be purified to
      homogeneity via the gel filtration chromatography on a Sephacryl S-200 column
      followed the affinity chromatography on a Ni-NTA column. The two sequential
      purification procedures yielded 4.3mg purified (His)(6)-tagged CI-b1 from 200ml
      of culture medium. Studies on (His)(6)-tagged CI-b1 revealed that three disulfide
      bonds were formed in the recombinant CI-b1 and the inhibitory properties of
      recombinant CI-b1 against alpha-chymotrypsin were similar to those of native CI
      b1. Recombinant CI-b1 immobilized on Ni-NTA resin was used to detect the
      interactions occurring between the CI-b1 and its target factors.

PMID- 15477077
TI  - Influence of promoter choice and trichostatin A treatment on expression of
      baculovirus delivered genes in mammalian cells.
AB  - The expression of recombinant proteins following transduction of CHO cells with
      recombinant baculoviruses containing a mammalian expression cassette with the CMV
      promoter is enhanced by the addition of trichostatin A (TSA), a specific histone
      deacetylase inhibitor. To further investigate the effect of TSA treatment on
      protein production following BacMam transduction, viruses containing various
      viral promoters (SV40, CMV, and RSV) and one cellular promoter (human ubiquitin
      C) were compared with regard to expression level of a gfp-luciferase fusion
      protein following transduction of CHO, COS-1, and HEK293 cells. The overall
      effect on expression appears to be cell specific, indicating that different
      mechanisms are active within different cell lines. Further, COS cells transfected
      with naked viral DNA, plasmids, and baculovirus particles were compared in regard
      to TSA treatment. The increase in reporter gene expression observed following
      BacMam transduction and TSA treatment were greater than those for transfection of
      either naked viral DNA or plasmid DNA.

PMID- 15477078
TI  - Expression, purification, and characterization of His-tagged penicillin G acylase
      from Kluyvera citrophila in Escherichia coli.
AB  - The DNA fragment encoding Kluyvera citrophila penicillin G acylase (KcPGA) was
      amplified and cloned into the vector pET28b to obtain a C-terminus His-tagged
      fusion expression plasmid. The fusion protein KcPGA was successfully
      overexpressed in Escherichia coli BL21(DE3). The optimal induction concentration
      of isopropylthio-beta-D-galactoside (IPTG) was found to be 5 microM. The fusion
      protein was purified in a single step by Ni-IDA affinity chromatograph to a
      specific activity of 35.3U/mg protein with a final yield of 89% representing a 23
      fold purification. The data presented here suggest that the purified fusion
      protein is stable with respect to pH and temperature. The optimal pH and
      temperature of recombinant KcPGA are 8.5 and 55 degrees C, respectively. The Km
      and Vmax are 17.6 microM and 23.8 U/mg, respectively. Therefore, the high yield
      and high specific activity of recombinant KcPGA produced in E. coli, together
      with other kinetic parameters, represent an excellent basis for further
      development of recombinant KcPGA as an immobilized biocatalyst for industrial
      applications.

PMID- 15477079
TI  - Extracellular expression and single step purification of recombinant Escherichia
      coli L-asparaginase II.
AB  - L-Asparaginase (isozyme II) from Escherichia coli is an important therapeutic
      enzyme used in the treatment of leukemia. Extracellular expression of recombinant
      asparaginase was obtained by fusing the gene coding for asparaginase to an
      efficient pelB leader sequence and an N-terminal 6x histidine tag cloned under
      the T7lac promoter. Media composition and the induction strategy had a major
      influence on the specificity and efficiency of secretion of recombinant
      asparaginase. Induction of the cells with 0.1 mM IPTG at late log phase of growth
      in TB media resulted in fourfold higher extracellular activity in comparison to
      growing the cells in LB media followed by induction during the mid log phase.
      Using an optimized expression strategy a yield of 20,950 UI/L of recombinant
      asparaginase was obtained from the extracellular medium. The recombinant protein
      was purified from the culture supernatant in a single step using Ni-NTA affinity
      chromatography which gave an overall yield of 95 mg/L of purified protein, with a
      recovery of 86%. This is approximately 8-fold higher to the previously reported
      data in literature. The fluorescence spectra, analytical size exclusion
      chromatography, and the specific activity of the purified protein were observed
      to be similar to the native protein which demonstrated that the protein had
      folded properly and was present in its active tetramer form in the culture
      supernatant.

PMID- 15477080
TI  - Site- and subunit-specific incorporation of unnatural amino acids into HIV-1
      reverse transcriptase.
AB  - A highly efficient cell-free translation system has been combined with suppressor
      tRNA technology to substitute nor-Tyr and 3-fluoro-Tyr in place of Tyr183 at the
      DNA polymerase active site of p66 of human immunodeficiency virus type 1 reverse
      transcriptase (HIV-1 RT). Supplementing the wild-type HIV-1 p51 RT subunit into
      this translation system permitted reconstitution of the biologically relevant
      p66/p51 heterodimer harboring Tyr analogs exclusively on the catalytically
      competent p66 subunit. Addition of an affinity tag at the p66 C-terminus allowed
      rapid, one-step purification of reconstituted and selectively mutated heterodimer
      HIV-1 RT via strep-Tactin-agarose affinity chromatography. The purified enzyme
      was demonstrated to be free of contaminating nucleases, allowing characterization
      of the DNA polymerase and ribonuclease H activities associated with HIV-1 RT.
      Preliminary characterization of HIV-1 RT(nor-Tyr) and HIV-1 RT(m-fluoro-Tyr) is
      presented. The success of this strategy will facilitate detailed molecular
      analysis of structurally and catalytically critical amino acids via their
      replacement with closely related, unnatural analogs.

PMID- 15477081
TI  - Expression and purification of the BmK Mm2 neurotoxin from the scorpion Buthus
      martensii Karsch and its biological activity test.
AB  - The gene encoding neurotoxin (BmK Mm2) from the scorpion Buthus martensii Karsch
      was expressed in Escherichia coli BL21 (DE3) at a level of 1.6 mg/L using
      expression plasmid pExSecI system. SDS-PAGE analysis of the cell lysate confirmed
      that gene BmK Mm2 was expressed in soluble form and the expressed production was
      secreted into Luria-Bertani (LB) culture medium from Escherichia coli. According
      to the characters of pExSecI expression system, the IgG binding domain-ZZ of
      Protein A is fused to the N-terminal of BmK Mm2. Recombinant BmK Mm2 (ZZ-BmK Mm2,
      pI 6.81, 22.007 kDa) was purified rapidly and efficiently by IgG-Sepharose 6 Fast
      Flow and Superdex-75 gel filtration chromatography, produced a single band on SDS
      PAGE. Western blot analysis demonstrated that this protein was recombinant BmK
      Mm2. The results of MTT assay, morphological observation of nucleus and single
      cell gel electrophoresis showed that the expressed recombinant BmK Mm2 was toxic
      for glial cells of mice, which indicate that it has biological activity.

PMID- 15477082
TI  - The role of thioredoxin and disulfide isomerase in the expression of the snake
      venom thrombin-like enzyme calobin in Escherichia coli BL21 (DE3).
AB  - Thrombin-like enzymes (TLEs) are studied widely because of their therapeutic
      potential in myocardial infarction and thrombotic diseases. But they are always
      produced in Escherichia coli BL21 (DE3) as inclusion bodies because they are
      single chain Cys-rich proteins. In this work, coexpressing of thioredoxin (TrxA)
      largely increased the solubility of calobin, one of the TLEs from korea viper
      Agkistrodon caliginosus, but soluble calobin-T had poor enzyme activity.
      Disulfide isomerase (DsbC) was introduced into the host cell and coexpressed with
      calobin in the presence of TrxA, the result was that both the solubility and
      enzyme activity of calobin-TD were higher than those of calobin-T. Although
      recombinant calobins exhibited the enzyme of hydrolyzing the fibrinogen, they
      lost clotting activity to the substrate. Recombinant calobin-TD remained poor
      amidolytic activity, the effects of divalent metal cations and various inhibitors
      on this activity were similar to those of native calobin nevertheless, suggesting
      that calobin-TD exhibited the characteristics of serine protease especially of
      trypsin-like serine protease.

PMID- 15477083
TI  - Expression, purification, and isotope labeling of cannabinoid CB2 receptor
      fragment, CB2(180-233).
AB  - To develop an approach to obtain milligram quantities of purified isotope-labeled
      seven transmembrane G-protein coupled cannabinoid (CB) receptor for NMR
      structural analysis, we chose a truncated CB receptor fragment, CB2(180-233),
      spanning from the fifth transmembrane domain (TM5) to the associated loop regions
      of cannabinoid CB2 receptor. This highly hydrophobic membrane protein fragment
      was pursued for developmental studies of membrane proteins through expression and
      purification in Escherichia coli. The target peptide was cloned and over
      expressed in a preparative scale as a fusion protein with a modified
      TrpDeltaLE1413 (TrpLE) leader sequence and a nine-histidine tag at its N
      terminal. An experimental protocol for enzyme cleavage was developed by using
      Factor Xa to remove the TrpLE tag from the fusion protein. A purification process
      was also established using a nickel affinity column and reverse-phase HPLC, and
      then monitored by SDS-PAGE and MS. This expression level is one of the highest
      reported for a G-protein coupled receptor and fragments in E. Coli, and provided
      a sufficient amount of purified protein for further biophysical studies.

PMID- 15477084
TI  - BgK, a disulfide-containing sea anemone toxin blocking K+ channels, can be
      produced in Escherichia coli cytoplasm as a functional tagged protein.
AB  - BgK, a sea anemone peptide consisting of 37 amino acid residues and 3 disulfide
      bonds, blocks voltage-gated potassium (Kv1) channels. Here, we report a method
      for producing tagged BgK in Escherichia coli, as a soluble cytoplasmic protein.
      First, using peptidic synthesis, we show that addition of a 15 residue peptide
      (S.Tag) at the BgK C-terminus does not affect its biological activity. Then, a
      synthetic DNA sequence encoding BgK was constructed and cloned to produce a BgK
      S.Tag hybrid in the cytoplasm of E. coli. The presence of S.Tag did not only
      facilitate detection, quantification, and purification of the recombinant
      protein, but also increased the production yield by more than two orders of
      magnitude. Moreover, use of an E. coli OrigamiB(DE3)pLacI strain also increased
      production; up to 5.8-7.5mg of BgK-S.Tag or mutated BgK(F6A)-S.Tag was produced
      per liter of culture and could be functionally characterized in crude extracts.
      Using a two-step purification procedure (affinity chromatography and RP-HPLC), we
      obtained 1.8-2.8mg of purified recombinant protein per liter of culture. The
      recombinant peptides displayed functional properties similar to those of native
      BgK or BgK(F6A).

PMID- 15477085
TI  - In vivo incorporation of selenomethionine in proteins using Pseudomonas
      aeruginosa as expression host: case study-the outer membrane receptor FpvA.
AB  - The number of protein structures solved using multiwavelength anomalous
      diffraction methods coupled with selenomethionine substitution has grown
      dramatically over the last years. We show using the outer membrane pyoverdin
      receptor FpvA that Pseudomonas aeruginosa can be used for producing proteins with
      a high level of selenomethionine incorporation. To circumvent problems
      encountered with mass spectroscopy analysis of purified membrane proteins, in-gel
      trypsin digestion of FpvA coupled with MALDI mass spectrometry analysis of the
      resulting peptides was used to determine the extent of selenomethionine
      incorporation. Selenomethionine incorporation greater than 95% was achieved using
      P. aeruginosa as an overexpression system.

PMID- 15477086
TI  - Purification of the recombinant human serotonin N-acetyltransferase (EC
      2.3.1.87): further characterization of and comparison with AANAT from other
      species.
AB  - Melatonin is synthesized by a series of enzymes, the penultimate one, serotonin N
      acetyltransferase, catalyzing the limiting reaction. In the present study, we
      compared the recombinant serotonin N-acetyltransferases from rat, ovine, and
      human. The human protein is particularly difficult to purify because it interacts
      strongly with a putative chaperone protein from bacteria whereas the rat and
      sheep enzymes, which interact less strongly with this protein, have been purified
      close to homogeneity. We identified the contaminating protein as GroEL, the
      bacterial equivalent of Hsp60. We present numerous catalytic activities
      (substrate and cosubstrate specificities as well as inhibitor specificities)
      measured on the three species enzymes from which we deduced that the presence of
      the chaperone might partly explain the differences between the various species
      enzyme characteristics, beside the inter-species ones resulting from sequence
      differences. Despite several trials reported in the literature, a purification to
      homogeneity of the human (recombinant) enzyme has never been described. We
      present a new purification method, by using an original denaturation/renaturation
      process in which the enzyme is immobilized on an affinity chromatography column.
      The enzyme is then eluted in an active and pure form (i.e., absence of
      chaperone). The up-scaled system permitted us to perform the necessary
      experiments for the measurement of more accurate affinities of human serotonin N
      acetyltransferase towards its main natural substrates, showing that only the
      activity of the enzyme towards phenylethylamine was modified.

PMID- 15477087
TI  - Rapid purification of the potato ADP-glucose pyrophosphorylase by polyhistidine
      mediated chromatography.
AB  - In an attempt to obtain facile methods to purify the heterotetrameric ADP-glucose
      pyrophosphorylase (AGPase), polyhistidine tags were attached to either the large
      (LS) or small (SS) subunits of this oligomeric enzyme. The addition of
      polyhistidine tag to the N-terminus of the LS or SS and co-expression with its
      unmodified counterpart subunit resulted in substantial induction of enzyme
      activity. In contrast, attachment of a polyhistidine-containing peptide through
      the use of a commercially available pET vector or addition of polyhistidine tags
      to the C-terminal ends of either subunit resulted in poor expression and/or
      production of enzyme activity. Preliminary experiment showed that these
      polyhistidine N-terminal-tagged enzymes interacted with Ni-NTA-agarose,
      indicating that immobilized metal affinity chromatography (IMAC) would be useful
      for efficient purification of the heterotetrameric AGPases. When ion-exchange
      chromatography step was employed prior to the IMAC, the polyhistidine-tagged
      AGPases were purified to near homogeneity. Comparison of kinetic parameters
      between AGPases with and without the polyhistidine tags revealed that attachment
      of the polyhistidine did not alter the allosteric and catalytic properties of the
      enzymes. These results indicate that polyhistidine tags will be useful for the
      rapid purification of preparative amounts of AGPases for biochemical and physical
      studies.

PMID- 15477088
TI  - Efficient site-specific processing of fusion proteins by tobacco vein mottling
      virus protease in vivo and in vitro.
AB  - Affinity tags are widely used as vehicles for the production of recombinant
      proteins. Yet, because of concerns about their potential to interfere with the
      activity or structure of proteins, it is almost always desirable to remove them
      from the target protein. The proteases that are most often used to cleave fusion
      proteins are factor Xa, enterokinase, and thrombin, yet the literature is replete
      with reports of fusion proteins that were cleaved by these proteases at locations
      other than the designed site. It is becoming increasingly evident that certain
      viral proteases have more stringent sequence specificity. These proteases adopt a
      trypsin-like fold but possess an unconventional catalytic triad in which Cys
      replaces Ser. The tobacco etch virus (TEV) protease is the best-characterized
      enzyme of this type. TEV protease cleaves the sequence ENLYFQG/S between QG or QS
      with high specificity. The tobacco vein mottling virus (TVMV) protease is a close
      relative of TEV protease with a distinct sequence specificity (ETVRFQG/S). We
      show that, like TEV protease, TVMV protease can be used to cleave fusion proteins
      with high specificity in vitro and in vivo. We compared the catalytic activity of
      the two enzymes as a function of temperature and ionic strength, using an MBP
      NusG fusion protein as a model substrate. The behavior of TVMV protease was very
      similar to that of TEV protease. Its catalytic activity was greatest in the
      absence of NaCl, but diminished only threefold with increasing salt up to 200 mM.
      We found that the optimum temperatures of the two enzymes are nearly the same and
      that they differ only two-fold in catalytic efficiency, both at room temperature
      and 4 degrees C. Hence, TVMV protease may be a useful alternative to TEV protease
      when a recombinant protein happens to contain a sequence that is similar to a TEV
      protease recognition site or for protein expression strategies that involve the
      use of more than one protease.

PMID- 15477089
TI  - Construct design, biophysical, and biochemical characterization of the fusion
      core from mouse hepatitis virus (a coronavirus) spike protein.
AB  - Membrane fusion between virus and host cells is the key step for enveloped virus
      entry and is mediated by the viral envelope fusion protein. In murine
      coronavirus, mouse hepatitis virus (MHV), the spike (S) protein mediates this
      process. Recently, the formation of anti-parallel 6-helix bundle of the MHV S
      protein heptad repeat (HR) regions (HR1 and HR2) has been confirmed, implying
      coronavirus has a class I fusion protein. This bundle is also called fusion core.
      To facilitate the solution of the crystal structure of this fusion core, we
      deployed an Escherichia coli in vitro expression system to express the HR1 and
      HR2 regions linked together by a flexible linker as a single chain (named 2
      helix). This 2-helix polypeptide subsequently assembled into a typical 6-helix
      bundle. This bundle has been analyzed by a series of biophysical and biochemical
      techniques and confirmed that the design technique can be used for coronavirus as
      we successfully used for members of paramyxoviruses.

PMID- 15477090
TI  - Expression of non-toxic mutant of Escherichia coli heat-labile enterotoxin in
      tobacco chloroplasts.
AB  - Chloroplast transformation systems offer unique advantages in biotechnology,
      including high level of foreign gene expression, maternal inheritance, and
      polycistronic expression. We studied chloroplast expression of LTK63 (change Ser-
      >Lys at position 63 in the A subunit) which is the mutant of Escherichia coli
      heat-labile toxin. LTK63 is devoid of any toxic activity, but still retains its
      mucosal adjuvanticity. The LTK63 was cloned into chloroplast targeting vector and
      transformed to tobacco chloroplasts by particle bombardment. PCR and Southern
      blot analyses confirmed stable homologous recombination of the LTK63 gene into
      the chloroplast genome. The amount of LTK63 protein detected in tobacco
      chloroplasts was approximately 3.7% of the total soluble protein. The GM1
      ganglioside binding assay confirmed that chloroplast-synthesized LTB of LTK63
      binds to the intestinal membrane GM1-ganglioside receptor. Thus, the expression
      of LTK63 in chloroplasts provides a potential route toward the development of a
      plant-based edible vaccine for high expression system and environmentally
      friendly approach.

PMID- 15477091
TI  - High-level expression of the neutralizing epitope of porcine epidemic diarrhea
      virus by a tobacco mosaic virus-based vector.
AB  - Porcine epidemic diarrhea virus (PEDV) causes acute enteritis in pigs of all ages
      and is often fatal for neonates. A tobacco mosaic virus (TMV)-based vector was
      utilized for the expression of a core neutralizing epitope of PEDV (COE) for the
      development of a plant-based vaccine. In this study, the coding sequence of a COE
      gene was optimized based on the modification of codon usage in tobacco plant
      genes and the removal of mRNA-destabilizing sequences. The native and synthetic
      COE genes were cloned into TMV-based vectors and expressed in tobacco plants. The
      recombinant COE protein constituted up to 5.0% of the total soluble protein in
      the leaves of tobacco plants infected with the TMV-based vector containing
      synthetic COE gene, which was approximately 30-fold higher than that in tobacco
      plants infected with TMV-based vector containing a native COE gene. Therefore,
      this result indicates that the plant viral expression system with a synthetic
      gene optimized for plant expression is suitable to produce a large amount of
      antigen for the development of plant-based vaccine rapidly.

PMID- 15477092
TI  - Purification, folding, and characterization of Rec12 (Spo11) meiotic recombinase
      of fission yeast.
AB  - Meiotic recombination is initiated by controlled dsDNA breaks (DSBs). Rec12
      (Spo11) protein of fission yeast is essential for the formation of meiotic DSBs
      in vivo, for meiotic recombination, and for segregation of chromosomes during
      meiosis I. Rec12 is orthologous to Top6A topoisomerase of Archaea and is likely
      the catalytic subunit of a meiotic recombinase that introduces recombinogenic
      DSBs. However, despite intensive effort, it has not been possible to produce
      Rec12 protein in a soluble form required to permit biochemical analyses of
      function. To obtain purified Rec12 protein for in vitro studies, a rec12(+) cDNA
      was generated, cloned into vector pET15b(+), and expressed in Escherichia coli.
      Rec12 protein was produced at moderate levels and it partitioned into insoluble
      fractions of whole-cell extracts. The protein was enriched based upon its
      differential solubility in two different denaturants and was further purified by
      column chromatography. A combinatorial, fractional, factorial approach was used
      to identify conditions under which Rec12 protein could be refolded. Four
      parameters were most important and, following optimization, soluble Rec12 protein
      was obtained. Gel filtration demonstrated that refolded Rec12 protein exists as a
      monomer in solution, suggesting that additional proteins may be required to
      assemble biologically-active Rec12 dimers, as inferred previously from genetic
      data [Cell Chromosome 1 (2002) 1]. The production of refolded Rec12 in a soluble
      form will allow for characterization in vitro of this key meiotic recombination
      enzyme.

PMID- 15477093
TI  - Production and purification of Bacillus anthracis protective antigen from
      Escherichia coli.
AB  - Anthrax is caused by the gram-positive, spore-forming bacterium, Bacillus
      anthracis. The anthrax toxin consists of three proteins, protective antigen (PA),
      lethal factor, and edema factor. Current vaccines against anthrax use PA as their
      primary component since it confers protective immunity. In this work, we
      expressed soluble, recombinant PA in relatively high amounts in the periplasm of
      E. coli from shake flasks and bioreactors. The PA protein was purified using Q
      Sepharose-HP and hydroxyapatite chromatography, and routinely found to be 96-98%
      pure. Yields of purified PA varied depending on the method of production;
      however, medium cell density fermentations resulted in approximately 370 mg/L of
      highly pure biologically active PA protein. These results exhibit the ability to
      generate gram quantities of PA from E. coli.

PMID- 15477094
TI  - Expression and purification of his-tagged rat peroxisomal acyl-CoA oxidase I wild
      type and E421 mutant proteins.
AB  - Rat peroxisomal acyl-CoA oxidase I is a key enzyme for the beta-oxidation of
      fatty acids, and the deficiency of this enzyme in patients has been previously
      reported. We cloned the gene of rat peroxisomal acyl-CoA oxidase I into a
      bacterial expression vector pLM1 with six continuous histidine codons attached to
      the 5' end of the gene. The cloned gene was overexpressed in Escherichia coli and
      the soluble protein was purified with a nickel HiTrap chelating metal-affinity
      column in 90% yield to apparent homogeneity. The specific activity of the
      purified His-tagged rat peroxisomal acyl-CoA oxidase I was 1.5 micromol/min/mg.
      It has been proposed that Glu421 is a catalytic residue responsible for
      deprotonation of alpha-proton of acyl-CoA substrate. We constructed four mutant
      expression plasmids of the enzyme, pACO(E421D), pACO(E421A), pACO(E421Q), and
      pACO(E421G) using site-directed mutagenesis. Mutant proteins were overexpressed
      in E. coli and purified with a nickel metal-affinity column. Kinetic studies of
      wild-type and mutant proteins were carried out, and the result confirmed that
      Glu421 is a catalytic residue of rat peroxisomal acyl-CoA oxidase I. Our
      overexpression in E. coli and one-step purification of the highly active N
      terminal His-tagged rat peroxisomal acyl-CoA oxidase I greatly facilitated our
      further investigation of this enzyme, and our result from site-directed
      mutagenesis increased our understanding of the mechanism for the reaction
      catalyzed by peroxisomal acyl-CoA oxidase I.

PMID- 15477095
TI  - The biology of desmin filaments: how do mutations affect their structure,
      assembly, and organisation?
AB  - Desmin, the major intermediate filament (IF) protein of muscle, is evolutionarily
      highly conserved from shark to man. Recently, an increasing number of mutations
      of the desmin gene has been described to be associated with human diseases such
      as certain skeletal and cardiac myopathies. These diseases are histologically
      characterised by intracellular aggregates containing desmin and various
      associated proteins. Although there is progress regarding our knowledge on the
      cellular function of desmin within the cytoskeleton, the impact of each distinct
      mutation is currently not understood at all. In order to get insight into how
      such mutations affect filament assembly and their integration into the
      cytoskeleton we need to establish IF structure at atomic detail. Recent progress
      in determining the dimer structure of the desmin-related IF-protein vimentin
      allows us to assess how such mutations may affect desmin filament architecture.

PMID- 15477096
TI  - Intrinsic versus mutation dependent instability/flexibility: a comparative
      analysis of the structure and dynamics of wild-type transthyretin and its
      pathogenic variants.
AB  - Transthyretin (TTR) is one of the about 20 known human proteins associated with
      amyloidosis which is characterized by the accumulation of amyloid fibrils in
      tissues or extracellular matrix surrounding vital organs. Unlike Alzheimer's
      fibrils that comprise a fragment of a large precursor protein, TTR amyloid
      fibrils are composed of both full-length protein and fragments of the molecule.
      The native state of TTR is a homotetramer with eight beta-strands organized into
      a beta-sandwich in each monomer. To elucidate the structural reorganization
      mechanisms preceding amyloid formation, it is important to characterize the
      dynamic features of the wild-type native state as well as to reveal the influence
      of disease-associated mutations on the structure and dynamics. Molecular dynamics
      (MD) simulations complement X-ray crystallography and D-H exchange to capture the
      intrinsically unstable/flexible sites of the wild-type as well as the mutation
      dependent unstable sites of the pathogenic variants. Our results of MD
      simulations have shown that the Leu55-->Pro (L55P) mutation occurs in an
      intrinsically unstable site, leading to substantial local and global structural
      changes. This observation supports the early speculation that the C-strand-loop-D
      strand rearrangement leads to the formation of amyloidogenic intermediates. In
      addition to the D strand, the alpha-helical region and the strands at the monomer
      monomer interface are also intrinsically unstable. The central channel of L55P
      TTR undergoes opening and closing fluctuations, which may provide an explanation
      for the fact that while the mutation is far from the channel, the mutant shows a
      substantial low binding affinity of thyroxine.

PMID- 15477097
TI  - Rational design of lipid for membrane protein crystallization.
AB  - The lipidic cubic phase has been used to grow crystals of membrane proteins for
      high-resolution structure determination. However, the original, so-called, in
      meso method does not work reliably at low temperatures, where proteins are
      generally more stable, because the hosting lipid turns solid. The need existed
      therefore for a lipid that forms the cubic phase and that supports crystal growth
      at low temperatures. We created a database of phase diagrams and used it to
      design such a lipid. X-ray diffraction showed that the new lipid exhibits
      designed phase behavior. Further, it produces diffraction quality membrane
      protein crystals by the in meso method at 6 degrees C. This demonstrates that
      lipidic materials, like their protein counterparts are amenable to rational
      design. The same approach as used in this study should find application in
      extending the range of membrane proteins crystallizable by the in meso method and
      in tailoring transport of cubic phases for controlled delivery and uptake.

PMID- 15477098
TI  - Assemblages of prion fragments: novel model systems for understanding amyloid
      toxicity.
AB  - We report the conformational and toxic properties of two novel fibril-forming
      prion amyloid sequences, GAVVGGLG (PrP(119-126)) and VVGGLGG (PrP(121-127)). The
      conformational preferences of these fragments were studied in differing
      microenvironments of TFE/water mixtures and SDS solution. Interestingly, with an
      increase in TFE concentration, PrP(119-126) showed a helical conformational
      propensity, whereas PrP(121-127) adopted a more random coil structure. In 5% SDS,
      PrP(119-126) showed more alpha-helical content than in TFE solution, and PrP(121
      127) exhibited a predominantly random coil conformation. However, both peptides
      took a random coil conformation in water, and over time the random coil
      transformed into a beta-sheet structure with a significant percentage of helical
      conformation and beta-turn structure in PrP(119-126) and PrP(121-127),
      respectively, as observed with CD spectroscopy. The aged fibrils of PrP(119-126)
      were insoluble in SDS, and PrP(121-127) was extractable with SDS solution. These
      fibrils were characterized by transmission electron microscopy. Both PrP(119-126)
      and PrP(121-127) formed stable monolayer's consisting of multimeric assemblages
      at the air-water interface. Monomeric PrP(119-126) was more toxic to astrocytes
      than the control Abeta peptide; however, the fibrillar form of PrP(119-126) was
      less toxic to astrocytes. PrP(121-127) elicited moderate toxicity in both soluble
      and fibrillar forms on astrocytes. Furthermore, quenching experiments using
      acroyl-labeled PrP(119-126) and PrP(121-127) with eosin-labeled synaptosomal
      membrane revealed that these prion fragments bind to anion-exchange protein. The
      binding of PrP(119-126) and PrP(121-127) with a membrane microdomain (lipid raft)
      was also analyzed using pyrenated derivatives. We conclude that the formation of
      PrP(119-126) and PrP(121-127) fibrils is a concentration-dependent process that
      involves coil to sheet conversion with aging. PrP(119-126), the sequence with
      intrinsic helical propensity, is more toxic in monomer form, and the fibril
      formation in this case seems to be protective to cells. For PrP(121-127), the SDS
      soluble fibrils are more cytotoxic, indicating that a higher order assemblage
      structure is required for cytotoxic activity of this peptide.

PMID- 15477099
TI  - XMIPP: a new generation of an open-source image processing package for electron
      microscopy.
AB  - X-windows based microscopy image processing package (Xmipp) is a specialized suit
      of image processing programs, primarily aimed at obtaining the 3D reconstruction
      of biological specimens from large sets of projection images acquired by
      transmission electron microscopy. This public-domain software package was
      introduced to the electron microscopy field eight years ago, and since then it
      has changed drastically. New methodologies for the analysis of single-particle
      projection images have been added to classification, contrast transfer function
      correction, angular assignment, 3D reconstruction, reconstruction of crystals,
      etc. In addition, the package has been extended with functionalities for 2D
      crystal and electron tomography data. Furthermore, its current implementation in
      C++, with a highly modular design of well-documented data structures and
      functions, offers a convenient environment for the development of novel
      algorithms. In this paper, we present a general overview of a new generation of
      Xmipp that has been re-engineered to maximize flexibility and modularity,
      potentially facilitating its integration in future standardization efforts in the
      field. Moreover, by focusing on those developments that distinguish Xmipp from
      other packages available, we illustrate its added value to the electron
      microscopy community.

PMID- 15477100
TI  - Crystallographic studies of ligand binding by Zn-alpha2-glycoprotein.
AB  - Zn-alpha2-glycoprotein (ZAG) is a 41 kDa soluble protein that is present in most
      bodily fluids. The previously reported 2.8 A crystal structure of ZAG isolated
      from human serum demonstrated the structural similarity between ZAG and class I
      major histocompatibility complex (MHC) molecules and revealed a non-peptidic
      ligand in the ZAG counterpart of the MHC peptide-binding groove. Here we present
      crystallographic studies to explore further the nature of the non-peptidic ligand
      in the ZAG groove. Comparison of the structures of several forms of recombinant
      ZAG, including a 1.95 A structure derived from ZAG expressed in insect cells,
      suggests that the non-peptidic ligand in the current structures and in the
      structure of serum ZAG is a polyethylene glycol (PEG), which is present in the
      crystallization conditions used. Further support for PEG binding in the ZAG
      groove is provided by the finding that PEG displaces a fluorophore-tagged fatty
      acid from the ZAG binding site. From these results we hypothesize that our
      purified forms of ZAG do not contain a bound endogenous ligand, but that the ZAG
      groove is capable of binding hydrophobic molecules, which may relate to its
      function.

PMID- 15477101
TI  - Backbone dynamics of oxidised and reduced forms of human atrial natriuretic
      peptide.
AB  - The backbone dynamics of the 28 residue 15N-labelled human atrial natriuretic
      peptide have been examined by 15N NMR methods. 15N R1, R2 and [1H]-15N NOE values
      were determined for the oxidised and reduced forms of the peptide (ANPox and
      ANPrd, respectively), and analysed using reduced spectral density mapping and an
      extended model-free approach. The two forms possessed correlation times for
      overall molecular motion of 4.7 ns and were highly flexible, with substantial
      contributions to relaxation processes from internal motions on picosecond to
      nanosecond time scales. Reduction of the Cys7-Cys23 disulphide bond to form ANPrd
      produced a very dynamic linear peptide with a mean overall order parameter of
      0.2; the intramolecular cross-link in ANPox increased this to a mean value of
      0.4. A simple model for segmental backbone motion accounted for the R2 values of
      both species using only two variable parameters, indicating that relaxation is
      dominated by interactions with sites <7 residues distant in the covalent network
      and that changes in the conformation of the disulphide bond lead to significant
      chemical exchange broadening in ANPox. The contributions of backbone dynamics to
      configurational entropy were determined and accounted for the different receptor
      binding affinities of cyclised and linear natriuretic peptides.

PMID- 15477102
TI  - Structural insights and functional implications of choline acetyltransferase.
AB  - The biosynthetic enzyme for the neurotransmitter acetylcholine, choline
      acetyltransferase (ChAT) (E.C. 2.3.1.6), is essential for the development and
      neuronal activities of cholinergic systems involved in many fundamental brain
      functions. ChAT catalyzes the transfer of an acetyl group from acetyl-coenzyme A
      to choline to form the neurotransmitter acetylcholine. Since its discovery more
      than 60 years ago much research has been devoted to the kinetic studies of this
      enzyme. For the first time we report the crystal structure of rat ChAT (rChAT) to
      1.55 A resolution. The structure of rChAT is a monomer and consists of two
      domains with an interfacial active site tunnel. This structure, with the modeled
      substrate binding, provides critical insights into the molecular basis for the
      production of acetylcholine and may further our understanding of disease causing
      mutations.

PMID- 15477103
TI  - Single particle analysis of filamentous and highly elongated macromolecular
      assemblies.
AB  - The application of single particle techniques to the three-dimensional analysis
      of electron microscope images of elongated or filamentous macromolecular
      assemblies is evaluated, taking as an example the muscle thin filament. Although
      the thin filament contains local helical symmetry, because of the inherent
      variable twist along it, the helical coherence does not extend for large enough
      distances to allow the symmetry to be used for full reconstruction of the
      tropomyosin/troponin repeat along the filament. The muscle thin filament
      therefore represents a general case of a filamentous object in that it is not
      possible to exploit symmetry in a full analysis. Due to the nature of the imaging
      process in the electron microscope, only projections of the thin filament around
      its long axis are available without tilting the grid. Crucially, projection
      images around a single axis do not provide enough information to assign Euler
      angles ab initio using current methods. Tests with a model thin filament
      structure indicated that an out-of-plane tilt of approximately 20 degrees was
      needed for ab initio angular assignment of sufficient accuracy to calculate a 3D
      structure to a resolution of approximately 25 A. If no out-of-plane views are
      available, an alternative approach is to use a prior 3D model as a reference for
      the initial angle assignment. Tests with the thin filament model indicated that
      reasonably accurate angular assignment can be made using a reference containing
      actin, but lacking the regulatory proteins tropomyosin and troponin. We also
      found that an adaptation of the exact filtered back projection method is required
      to allow the correct weighting of projection images in which the particle has a
      very large axial ratio. This adaptation resulted in significant improvements in
      the reconstruction.

PMID- 15477104
TI  - Crystal structure of the putative adapter protein MTH1859.
AB  - MTH1859 from Methanobacterium thermoautotrophicum is a 77 residue protein
      representing a conserved family of functionally uncharacterized proteins. We
      solved the crystal structure of MTH1859 by single wavelength anomalous
      diffraction phasing using selenomethionine labeled protein. MTH1859 adopts a
      mainly anti-parallel all-beta-fold. The beta-sheet is heavily bent to form a U
      structure that is closed through a loop. The monomer structure possesses
      similarities to the photoreaction center (PRC) domain fold, but the protein
      employs a unique oligomerization scheme. Two monomers of MTH1859 occupy the
      asymmetric unit and dimerize in a head-to-head fashion. Crystal packing
      interactions identify a second protein-protein interaction interface at the
      MTH1859 tails which can simultaneously bind two partner molecules. These
      interactions lead to the formation of a honeycomb structure and suggest that the
      family of MTH1859-like proteins might function as adapters for protein complex
      assembly.

PMID- 15477105
TI  - Strategies to optimize the use of currently available lung donors.

PMID- 15477107
TI  - Cardiac transplantation for amyloid heart disease: the United Kingdom experience.
AB  - BACKGROUND: Heart transplantation (TX) for cardiac amyloidosis is uncommon
      because of concern about progression of amyloid in other organs and the
      possibility of amyloid deposition in the donor heart. METHODS: Records of all 24
      patients with amyloid heart disease who have undergone TX in the United Kingdom
      were examined. Seventeen patients had AL amyloidosis (AL) and 7 had non-AL forms
      of amyloidosis (non-AL). RESULTS: Survival of the 10 patients with AL who
      underwent TX but had no additional chemotherapy was 50%, 50%, and 20% at 1, 2,
      and 5 years, respectively; amyloid recurred in the grafts of these patients after
      a median of 11 months, and extra-cardiac amyloid deposition contributed to
      mortality in 70% of these patients. Survival of 7 patients with AL who also had
      chemotherapy was 71%, 71%, and 36% respectively and 2 patients remain alive.
      Survival of the 7 patients with non-AL was 86%, 86%, and 64% at 1, 2, and 5
      years, respectively; 5 patients remain alive. One patient from this group had
      recurrence of amyloid in the graft at 60 months. Five-year survival for all 24
      amyloid patients was 38%, compared to patients undergoing TX in the UK for other
      indications (n = 4,058) for whom it was 67% (p = 0.013). CONCLUSION: Regardless
      of the use of adjunctive chemotherapy, the 5-year survival after TX for cardiac
      AL amyloidosis was less than that after TX for other indications, and progression
      of the systemic disease contributed substantially to the increased mortality. In
      contrast, the 5-year survival after TX for non-AL amyloid, combined as necessary
      with liver or kidney TX, was similar to that after TX in general.

PMID- 15477106
TI  - HLA-specific antibodies are associated with high-grade and persistent-recurrent
      lung allograft acute rejection.
AB  - BACKGROUND: The impact of HLA-specific antibodies is not well established in the
      acute rejection of lung allografts. Acute rejection represents the most important
      risk factor for the development of chronic lung allograft dysfunction. METHODS:
      We analyzed the pattern of HLA antibodies before and after transplantation in 54
      patients, and correlated our data with the presence and frequency of high-grade
      and persistent-recurrent acute rejection, during the first 18 post-operative
      months. The diagnosis of acute rejection was based on histologic International
      Society for Heart and Lung Transplantation (ISHLT)-published criteria. RESULTS:
      Ten of 54 patients had a positive enzyme-linked immunoassay (ELISA) post
      transplantation. In 90% of ELISA-positive patients, the presence of HLA
      antibodies was associated with persistent-recurrent acute rejections, compared
      with 34% in the ELISA-negative group (p < 0.005). There were 28 high-grade acute
      rejection episodes in the ELISA-positive group, compared with 36 in the ELISA
      negative group (p < 0.0001). The ELISA-positive patients required a greater
      intensity of immunosuppressive therapy. The patients with ELISA-detected anti-HLA
      antibodies were at least 3-fold more likely to develop high-grade acute rejection
      and persistent-recurrent acute rejection, and 7-fold more likely to develop
      multiple episodes of persistent-recurrent acute rejection, compared with ELISA
      negative patients. CONCLUSIONS: ELISA-based screening for the development of HLA
      antibodies is a reliable method that can identify lung transplant recipients at
      increased risk for high-grade and persistent-recurrent acute rejection. Although
      bronchiolitis obliterans appears as a point of no return in the evolution of lung
      transplanted patients, early detection of risk factors for acute rejection could
      indirectly decrease the incidence of bronchiolitis obliterans. These lung
      transplanted patients may benefit from an altered strategy of immunosuppression.

PMID- 15477108
TI  - Ventilatory response to exercise and kinetics of oxygen recovery are similar in
      cardiac transplant recipients and patients with mild chronic heart failure.
AB  - BACKGROUND: Exercise capacity, assessed by cardiopulmonary exercise treadmill
      testing (CPET), does not return to normal following heart transplantation. This
      study evaluated the ventilatory response to exercise and the kinetics of oxygen
      (O(2)) recovery in heart transplant recipients (HTR) compared to healthy
      volunteers (HV) and heart failure patients. METHODS: Eighteen patients with end
      stage heart failure (ESHF), 12 with mild heart failure (MHF) matched for peak
      oxygen consumption (Vo(2)) with the HTR, 12 HTR and 12 HV underwent CPET for
      measurements of peak Vo(2), Vo(2) at anaerobic threshold (AT), first-degree slope
      of Vo(2) decline during early recovery (Vo(2)/t-slope), time required for a 50%
      fall from peak Vo(2) (T(1/2) of Vo(2)) and the slopes of VE/Vco(2) and VE/Vo(2).
      RESULTS: The MHF and HTR groups had similar ventilatory responses to exercise and
      O(2) recovery kinetics. Peak Vo(2) (18.5 +/- 5.7 vs 9.4 +/- 0.9 ml/kg/min, p <
      0.001), AT (13.8 +/- 4.8 vs 6.7 +/- 1.8 ml/kg/min, p < 0.001) and Vo(2)/t-slope
      (0.6 +/- 0.2 vs 0.3 +/- 0.2 liter/min/min, p = 0.055) were higher in the HTR than
      in the ESHF group. In contrast, HTR had lower VE/Vco(2)-slope (31.4 +/- 3.8 vs
      39.2 +/- 9.9, p = 0.015) and T(1/2) Vo(2) (1.5 +/- 0.3 vs 2.4 +/- 1.1 minute, p =
      0.014) than the ESHF group. Compared to HV, HTR had lower Vo(2) peak (18.5 +/-
      5.7 vs 28.4 +/- 6.9 ml/kg/min, p < 0.001), AT (13.8 +/- 4.8 vs 19.8 +/- 4.5
      ml/kg/min, p = 0.04), Vo(2)/t-slope (0.6 +/- 0.2 vs 1.0 +/- 0.4 liter/min/min, p
      = 0.005) and steeper VE/Vco(2) slope (31.4 +/- 3.8 vs 23.6 +/- 2.7, p = 0.062).
      Heart rate deceleration during recovery was significantly slower in HTR than in
      all other groups. CONCLUSIONS: Exercise intolerance and delayed O(2) recovery
      kinetics were only partially reversed after heart transplantation. This finding
      suggests that some of the pathophysiologic mechanisms of heart failure persist
      after heart transplantation.

PMID- 15477109
TI  - Tricuspid annuloplasty significantly reduces early tricuspid regurgitation after
      biatrial heart transplantation.
AB  - BACKGROUND: The incidence of tricuspid annuloplasty (TR) observed early after
      cardiac biatrial implantation is unpredictable and in our experience not
      infrequently problematic. Although the bicaval method of implant may reduce the
      incidence of TR, its benefit has not been conclusively documented. METHODS: In an
      attempt to reduce the incidence of TR observed early after cardiac
      transplantation, 25 consecutive patients undergoing cardiac transplantation
      received donor heart tricuspid annuloplasty (TA) with either a DeVega or Ring
      technique. Early transthoracic echocardiograms were analyzed and compared with an
      immediately prior and consecutive cohort of 25 patients undergoing
      transplantation without TA. The biatrial technique of cardiac transplantation
      with a Cabrol modification was used for donor heart implant in both groups.
      Echocardiograms obtained 5 days after cardiac transplantation were reviewed in
      blinded fashion. TR was scored 0 = none, 1 = mild, 2 = moderate, and 3 = severe.
      RESULTS: Donor and recipient characteristics were not different between groups.
      No hospital deaths occurred in either group. Patients undergoing transplantation
      without TA had a higher TR score, 1.3 (range 0-3), than did patients with TA, 0.7
      (range 0-1.5, p = 0.002). Moderate or severe TR was present in 8 of 25 patients
      without TA compared with 0 of 25 patients with TA (p = 0.004). No patients
      required permanent pacemaker. CONCLUSIONS: TA can significantly reduce the
      incidence of early postoperative TR after biatrial cardiac transplant without
      adding to the complexity of operation.

PMID- 15477110
TI  - ONO-4817, a novel matrix metalloproteinase inhibitor, attenuates allograft
      vasculopathy in a rat cardiac transplant.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV), a disorder characterized by
      rapid development and progression of obliterative vasculopathy in the
      transplanted heart, continues to be a major cause of graft failure in long
      surviving human transplants. The mechanisms and histopathologic processes of CAV
      remain unknown. Previous animal studies have shown that inhibition of matrix
      metalloproteinase (MMP) prevents migration and proliferation of smooth muscle
      cells in CAV. In this study, we hypothesized that MMPs may be expressed in and
      may play an important role in CAV. METHODS: An F344-to-WKAH rat heterotopic heart
      transplantation model was used. Tacrolimus was administered intramuscularly 14
      days after transplantation to prevent acute rejection and to allow the
      development of CAV. We divided the animals into 2 groups according to post
      operative treatment: an ONO group received an MMP inhibitor (ONO-4817) daily by
      oral gavage for 14 days after transplantation (n = 6), and a control (n = 6)
      group received no treatment. Grafts were harvested 60 days after treatment.
      RESULTS: Immunohistochemical staining revealed that MMP-2 and tissue inhibitors
      of metalloproteinase-2 (TIMP-2) were expressed more strongly in the neointima and
      media of the control CAV animals than in the ONO-CAV animals. The animals given
      ONO-4817 exhibited a significant decrease in the percentage of affected vessels,
      in the percentage of intimal proliferation, in the intima-to-media ratio, and in
      the expression of MMP-2 and TIMP-2. CONCLUSION: These results suggest that MMP-2
      and TIMP-2 play an important role in the development of CAV and that the use of
      an MMP inhibitor (ONO-4817) may prevent neointimal proliferation in patients with
      CAV.

PMID- 15477111
TI  - Cyclosporine C2 monitoring improves renal dysfunction after lung transplantation.
AB  - BACKGROUND: Cyclosporine (CyA) toxicity is a potential cause of renal
      dysfunction, which occurs in 38% of lung transplant (LTx) recipients within 5
      years. Reducing CyA to "sub-therapeutic" trough (C0) levels increases the risk of
      rejection. The 2-hour post-dose concentration (C2) is favored as the best single
      point surrogate measure of CyA area under the curve (AUC), which reflects drug
      exposure. In this investigation we assess the effect of conversion to CyA C2
      monitoring on renal dysfunction after LTx. METHODS: Fifteen patients (M:F =
      12:3), aged 47 +/- 14 years (range 28 to 62), 3.5 +/- 2.7 (0.2 to 9.0) years post
      LTx, with C0 in the therapeutic range (maintenance 100 to 200 microg/liters)
      (Behring/EMIT immunoassay) and abnormal renal function, were converted from C0
      monitoring to C2 monitoring with dose reductions targeting C2 levels of 300 to
      600 microg/liter over a 12-month period. RESULTS: CyA dose was reduced from 6.4
      +/- 7.3 (1.2 to 27.9) to 3.1 +/- 2.7 (0.8 to 9.0) mg/kg/day (p = 0.04), with a
      reduction in C2 levels from 799 +/- 341 (299 to 1,466) to 390 +/- 148 (195 to
      675) microg/liter (p < 0.001). Improvements in serum creatinine (0.20 +/- 0.07
      [0.12 to 0.35] vs 0.16 +/- 0.04 [0.11 to 0.22] mmol/liter [p = 0.005]) were
      maintained during the study follow-up period of 1 year. Only 1 patient developed
      acute rejection and group mean forced expiratory volume in 1 second (FEV(1))
      remained stable (2.4 +/- 1.0 [1.1 to 4.0] vs 2.4 +/- 1.2 [1.1 to 4.6] liters).
      CONCLUSIONS: C2 monitoring is a practical method of improving renal dysfunction
      that allows safe dose reductions of CyA when formal AUC monitoring is not
      feasible. Extended use of this strategy is associated with long-term benefits.

PMID- 15477112
TI  - Cell-mediated immune response to influenza vaccination in lung transplant
      recipients.
AB  - BACKGROUND: Lung transplant recipients are susceptible to complications from
      influenza infection. Antibody responses to influenza vaccination have been shown
      to be decreased in lung transplant recipients. Cellular immune mechanisms serve
      an important role in influenza clearance. The cellular immune response to
      influenza vaccination has not been studied in transplant populations. METHODS:
      Interleukin-2, interleukin-10, interferon-gamma, and granzyme B levels to the
      three viral antigens included in the 1999 to 2000 influenza vaccine were measured
      before and 4 weeks post-vaccination in 43 lung transplant recipients and 21
      healthy adult controls. RESULTS: Interleukin-2, interleukin-10, interferon-gamma,
      and granzyme B levels did not increase from pre- to post-vaccination in the lung
      transplant group. Both pre- and post-cytokine levels were lower in the transplant
      group compared to the control group. Pre- and post-granzyme B levels did not
      differ significantly between the groups. The T-helper response in the control
      group varied with the different viral strains. A correlation between acute
      rejection episodes and the absence of both azathioprine and mycophenolate was
      found. CONCLUSIONS: Influenza vaccination does not stimulate a cell-mediated
      immune response in lung transplant recipients as judged by interleukin-2,
      interleukin-10, interferon-gamma, and granzyme B levels. Alternative prevention
      strategies may be needed.

PMID- 15477113
TI  - Hypertension as a marker for later development of end-stage renal failure after
      lung and heart-lung transplantation: a cohort study.
AB  - BACKGROUND: Time to renal failure after transplantation is not well known and the
      prognosis of lung and heart-lung transplantation with respect to end-stage renal
      failure and related factors has not been investigated in detail. We determined
      the predictors of end-stage renal failure after lung or heart-lung transplant
      using multivariate analysis. METHODS: A cohort study of 115 adult patients
      transplanted between 1990 and 1995, who survived at least 5 years, was carried
      out. Characteristics and clinical findings, including blood pressure, creatinine
      clearance and immunosuppression levels of patients with end-stage renal failure,
      were compared with those without, initially in a univariate analysis. Then a
      multivariate logistic regression model was built to examine the association of
      predictor variables with end-stage renal failure after adjustment for
      confounding. RESULTS: There were 19 of 115 (16.4%) patients with end-stage renal
      failure, with an average time of loss of renal function of 7.6 years (95%
      confidence interval [CI] 6.5 to 8.7) after transplantation. There was no
      difference in survival between patients with end-stage renal failure and those
      without. Multivariate analysis showed that development of hypertension post
      operatively was the only significant predictor variable (odds ratio 8.16, 95% CI
      1.01 to 66.0, p = 0.04). Patients' age at transplantation, gender, underlying
      medical conditions and other post-transplant features were not associated with
      end-stage renal failure. CONCLUSIONS: Development of hypertension after lung or
      heart-lung transplant should be used a marker for later development of end-stage
      renal failure. Any hypertension should be treated energetically. Acute renal
      failure immediately post-operatively did not predict end-stage renal failure in
      this cohort of patients.

PMID- 15477114
TI  - Aminoterminal pro type B natriuretic peptide as a predictive and prognostic
      marker in patients with chronic heart failure.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) is released from the cardiac
      ventricles in response to increased wall tension. We studied the relation of NT
      proBNP to Heart Failure Survival Score (HFSS) and New York Heart Association
      (NYHA) class in patients with chronic heart failure (CHF). We also studied the
      impact for recipient selection for cardiac transplant and assessed it as a
      predictive and prognostic marker of CHF. METHODS: A total of 550 patients with
      dilative cardiomyopathy (n = 323), and coronary artery disease (n = 227) were
      prospectively examined. All patients underwent spiroergometry, echocardiography,
      right heart catheterization, and electrocardiogram. Routine blood levels and NT
      proBNP were measured. The clinical selection for cardiac transplant candidates
      was adjudicated by 2 independent cardiologists who were blinded to the results of
      NT-proBNP assays. Clinical outcome and predictive power of NT-proBNP were
      analyzed. RESULTS: NT-proBNP levels in patients clinically considered for cardiac
      transplantation were significantly higher (2293 ng/ml vs 493 ng/ml; p < 0.001).
      The receiver operating characteristic (ROC) analysis regarding transplant
      candidacy showed an area under the ROC curve (AUC) of 0.84 +/- 0.01 for HFSS,
      0.86 +/- 0.001 for NYHA, and 0.96 +/- 0.01 for NT-proBNP. Patients with
      increasing NT-proBNP levels or remaining elevated levels despite adequate heart
      insufficiency treatment were maintained with left ventricular assist device
      implantation (n = 10) or urgent heart transplantation (n = 2). Patients with NT
      proBNP levels above 5000 pg/ml had a mortality rate of 28.4% per year. Twenty
      eight patients died during the observation period; all these patients were within
      NYHA Classes 3 and 4 (NT-proBNP 5423 +/- 423 ng/ml). CONCLUSIONS: NT-proBNP
      discriminates patients at high likelihood of being a candidate for
      transplantation and provides prognostic informations in patients with CHF. NT
      proBNP levels above 5000 pg/ml at admission were associated with death, and these
      levels markedly discriminated candidates for left ventricular assist devices or
      urgent transplantation.

PMID- 15477115
TI  - Reoxygenation results in cell death of human alveolar epithelial cells.
AB  - BACKGROUND: The functional response of isolated alveolar epithelial cells (AECs)
      to ischemia/reperfusion injury (I/R) is incompletely understood. Using a cell
      culture model, we investigated the tolerance of human type II alveolar cells
      (ATII) to hypoxia and subsequent reoxygenation. METHODS: Cell cultures of A549
      cells (human lung adenocarcinoma) and primary ATII were incubated in 95% N(2)/5%
      CO(2) saturated medium at 37 degrees C for 48 hours or 72 hours. The hypoxic
      medium was subsequently exchanged to normoxic medium at 37 degrees C. Lactate
      dehydrogenase (LDH) release and mitochondrial viability, as assessed by WST-1
      metabolism, were determined during both hypoxia and reoxygenation. A549 cells and
      ATII maintained under normoxic conditions served as controls. RESULTS: Before
      reoxygenation, after 48 or 72 hours of hypoxia, WST-1 metabolism in A549 cells
      was significantly reduced (p < 0.05), but LDH release remained low in both cell
      types. Reoxygenation after 48 h of hypoxia was associated with recovery of WST-1
      metabolism and an only minimal increase in LDH release. Reoxygenation after 72
      hours of hypoxia, in contrast, induced marked injury in both A549 cells and
      primary ATII as indicated by significantly reduced WST-1 metabolism and a
      dramatic increase of LDH release compared with normoxic controls (p < 0.05).
      CONCLUSIONS: Viability of alveolar cell lines and primary ATII is maintained
      during hypoxia for up to 72 hours. Reoxygenation after 72 hours of hypoxia
      results in rapid development of injury and cell death in both cell types.

PMID- 15477116
TI  - Electroanatomic and electrographic characterization of atrial flutter following
      cardiac transplantation: pre- and post-ablation.
AB  - A 20 year-old man developed recurrent symptomatic atrial flutter 9 years
      following cardiac transplantation. The clinical and electrophysiologic
      evaluations before and following successful ablation of the atrial flutter form
      the basis of this report.

PMID- 15477117
TI  - Fatal disseminated adenoviral infection in an adult heart transplant patient.
AB  - In heart transplant recipients, infection is one of the leading causes of
      morbidity and mortality. In adult heart transplant patients, cytomegalovirus is
      the most frequently encountered viral pathogen. Conversely, disseminated
      adenoviral infection is observed mainly in children, where it is predictive of
      allograft rejection and coronary vasculopathy. The literature contains only a few
      reports of adenoviral infections in adult heart transplant recipients. Limited
      information is available concerning the diagnosis and epidemiology of such
      infections and their relationship to organ rejection, heart failure and overall
      outcomes in these patients. To promote an awareness of this potentially lethal
      complication, we present a case of fatal disseminated adenoviral infection in an
      adult heart transplant recipient.

PMID- 15477118
TI  - Heme oxygenase-1 expression in alveolar macrophages is elevated in patients with
      bronchiolitis obliterans syndrome after lung transplantation.

PMID- 15477119
TI  - COPD at the 2004 9th European Pulmonary Summit.

PMID- 15477120
TI  - Potential genetic influences on the response to asthma treatment.
AB  - Genetic factors play a key role in determining the widely heterogeneous response
      to pharmacological treatment detectable among asthmatics. In particular,
      polymorphisms of the genes encoding relevant anti-asthma drug targets contribute
      significantly to such a variability. Therefore, it is very important to
      characterize asthmatic patient's genotypes and the related phenotypic patterns,
      in order to predict the individual therapeutic outcome. This pharmacogenetic
      approach will eventually help clinicians to optimize and personalize anti-asthma
      treatment, and will also provide useful information with regard to pre- and post
      marketing evaluation of both effectiveness and side effects of newly introduced
      drugs.

PMID- 15477121
TI  - N-acetylcysteine inhibits peroxynitrite-mediated damage in oleic acid-induced
      lung injury.
AB  - Since oleic acid (OA) induces morphologic and cellular changes similar to those
      observed in human acute lung injury (ALI) and acute respiratory distress
      syndrome, it has become a widely used model to investigate the effects of several
      agents on pathogenesis of lung injury. The antioxidant and anti-inflammatory
      properties of N-acetylcysteine (NAC) has been documented in many lung injury
      models. In this study, we evaluated the role of NAC in an OA-induced lung injury
      model by measuring myeloperoxidase (MPO) activity, malondialdehyde (MDA) and 3
      nitrotyrosine (3-NT) levels in lung tissue. Five groups labelled Sham, NAC, OA,
      Pre-OA-NAC and Post-OA-NAC were determined. ALI was induced by intravenous
      administration of OA. The pre-OA-NAC group received iv NAC 15 min before OA
      infusion and the post-OA-NAC group received iv NAC 2 h after OA infusion. In both
      of the NAC treatment groups' blood and tissue samples were collected 4 h after OA
      infusion, independent from the time of NAC infusion. The MPO activity, MDA and 3
      NT levels in lung homogenates were found to be increased in OA group and the
      administration of NAC significantly reduced tissue MPO, MDA and 3-NT levels (p =
      0.0001) Lung histopathology was also affected by NAC in this OA-induced
      experimental lung injury model.

PMID- 15477122
TI  - Relationship between neutrophil elastase and acute lung injury in humans.
AB  - We conducted clinical trials in patients with acute lung injury (ALI) associated
      with systemic inflammatory response syndrome using a selective neutrophil
      elastase inhibitor, sivelestat sodium hydrate (Sivelestat), to investigate the
      involvement of neutrophil elastase in ALI. In the phase III double-blind study
      (Study 1) in 230 patients, the efficacy of Sivelestat was evaluated with the
      pulmonary function improvement (PFI) rating as the primary endpoint, and the
      weaning rate from mechanical ventilator, the discharge rate from intensive care
      unit (ICU), and the survival rate as secondary endpoints. Afterwards, an
      unblinded study (Study 2) in 20 patients was conducted using procedures for
      weaning from mechanical ventilation to reevaluate its efficacy with ventilator
      free days (VFD) value, the primary endpoint, and to compare with that of Study 1
      subgroup, which met the selection criteria used in Study 2. Sivelestat increased
      PFI rating, reduced duration of mechanical ventilation, and shortened stay in ICU
      in Study 1, although there was no significant efficacy on the survival rate. VFD
      value in Study 2 was comparable to that in the optimal-dose group of Study 1
      subgroup, and increase in VFD value correlated with PFI rating and increase in
      ICU free days. It was concluded that neutrophil elastase may be involved in the
      pathogenesis of ALI in humans.

PMID- 15477123
TI  - Inhibitory activity of 1,8-cineol (eucalyptol) on cytokine production in cultured
      human lymphocytes and monocytes.
AB  - BACKGROUND: The therapeutic value of secretolytic agents in COPD and asthma is
      still disputed. For this reason, in a preclinical study we aimed to test the
      potential anti-inflammatory efficacy of 1,8-cineol (eucalyptol) in inhibiting
      polyclonal stimulated cytokine production by human unselected lymphocytes and LPS
      stimulated monocytes. METHODS: Cytokine production was determined following 20 h
      of incubation cells with 1,8-cineol simultaneously with the stimuli in culture
      supernatants by enzyme immunoassay. RESULTS: Therapeutic concentrations of 1,8
      cineol (1.5 microg/ml=10(-5)M) inhibited significantly (n=13-19, p=0.0001)
      cytokine production in lymphocytes of TNF-alpha > IL-1beta> IL-4> IL-5 by 92, 84,
      70, and 65%, respectively. Cytokine production in monocytes of TNF-alpha > IL
      1beta> IL-6> IL-8 was also significantly (n=7-16, p<0.001) inhibited by 99, 84,
      76, and 65%, respectively. In the presence of 1,8-cineol (0.15 microg/ml=10(-6)M)
      production of TNF-alpha>IL-1beta by monocytes and of IL-1beta> TNF-alpha by lymph
      ocytes was significantly inhibited by 77, 61 and by 36, 16%, respectively. 1,8
      cineol (10(-6)M) had a larger impact on TNF-alpha and IL-1beta-production in
      monocytes compared to lymphocytes (p<0.03) and similar effects (p>0.59) at
      therapeutically relevant concentrations of 1,8-Cineol (10(-5)M). CONCLUSION:
      These results characterize 1,8-cineol as strong inhibitor of TNF-alpha and IL
      1beta and suggest smaller effects on chemotactic cytokines. This is increasing
      evidence for the role of 1,8-cineol to control airway mucus hypersecretion by
      cytokine inhibition, suggesting long-term treatment to reduce exacerbations in
      asthma, sinusitis and COPD.

PMID- 15477124
TI  - Comparative effects of dopamine and dobutamine on hypercapnic depression of
      diaphragmatic contractility in dogs.
AB  - The present study was undertaken to evaluate the effects of dopamine and
      dobutamine on diaphragmatic contractility in dogs with induced hypercapnia.
      Animals were divided into three groups of ten each. In each group, hypercapnia
      (80-90 mmHg) was produced by adding 10% CO2 to the inspired gas. When hypercapnia
      was established, Group I received no study drug; Group II was infused with
      dopamine 10 microg/kg/min; Group III was infused with dobutamine 10
      microg/kg/min. Study drugs were administered intravenously for 60 min.
      Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi). In
      the presence of hypercapnia, in each group, Pdi at low-frequency (20-Hz) and high
      frequency (100-Hz) stimulation decreased from baseline (P<0.05). In Groups II and
      III, during the study drug administration, Pdi at both stimuli increased from
      hypercapnia-induced values (P<0.05). The increase in Pdi was more than in Group
      III than in Group II (P<0.05). In Group I, Pdi to each stimulus did not change
      from hypercapnia-induced values. In conclusion, compared with dopamine,
      dobutamine is effective in improving hypercapnic depression of diaphragmatic
      contractility in dogs.

PMID- 15477125
TI  - Effects of inhaled formoterol compared with salbutamol in ventilated preterm
      infants.
AB  - BACKGROUND: Short-acting beta(2)-agonists have shown beneficial effects in
      preterm infants, but data on long acting beta(2)-agonists are still lacking.
      OBJECTIVES: To compare the effects of inhaled formoterol with salbutamol in
      preterm infants. METHODS: Randomized, double-blind, crossover design of
      salbutamol (100 microg every 6 h) or formoterol (12 microg every 12 h) delivered
      by metered dose inhaler on two consecutive days to very low birth weight infants
      on assisted mechanical ventilation (n=12; gestational age 25.7+/-2 weeks; birth
      weight 720+/-254 g; postnatal age 25+/-9 days; mean+/-SD). Treatment with the
      second drug was administered until day 7 in eight infants. Outcome variables were
      minute volume MV, respiratory mechanics, heart rate HR, blood pressure, serum
      potassium and blood glucose levels. RESULTS: Mean MV increased by maximal 26%
      (salbutamol) and by 22% (formoterol) differing from baseline values until 6 and 8
      h through increased mean tidal volume (Vt) in both groups (max. 14%). Mean static
      compliance (Crs) increased by 26% (salbutamol) and by 32% (formoterol) until 60
      min post-administration. There was no tachyphylaxis. CONCLUSION: Inhaled
      salbutamol and formoterol equally increase MV, Vt, Crs and HR in mechanically
      ventilated infants with a longer lasting systemic effect of formoterol.

PMID- 15477126
TI  - Modulation of tracheal smooth muscle responses in inducible T-cell kinase
      knockout mice.
AB  - It has been shown that the Tec family nonreceptor tyrosine kinase inducible T
      cell kinase (ITK) plays a role in the activation of naive T cells and in the
      differentiation of T helper (TH2)-type cells producing cytokines in a model of
      allergic inflammation, thereby possibly indirectly mediating hyperresponsivenes
      of airway smooth muscle tone. Using excised tracheae from wild type (WT) mice and
      those lacking ITK, we conducted a series of in vitro experiments in which
      isometric smooth muscle tones were assessed in response to several agonists to
      determine whether the absence of ITK would affect the responsiveness of tracheal
      smooth muscle cells. The resulting change in contractile responses was evaluated
      by measuring agonist cumulative concentration-response curves (CCRC). Our results
      indicate that the cholinergic agonist acetylcholine (ACh) and its analog
      carbachol (CCh) exhibited comparable CCRC profiles in contracting isolated
      tracheae from both WT and ITK-/- mice, with no alteration in their efficacies.
      However, the EC50 values for the two agonists were found to be significantly
      higher in ITK-/- tracheae than in those from WT mice, suggesting an alteration of
      the potencies of these cholinergic agonists in the trachea of ITK-/- mice.
      Moreover, we found that the depolarizing agent potassium chloride (KCl) had a
      significantly lower efficacy in contracting ITK-/- tracheae compared to those
      from WT mice. This difference in KCl efficacy was abolished in the presence of a
      calcium (Ca2+) voltage-dependent channel (VDC) agonist, Bay K8644, suggesting a
      modulation of the KCl induced permeability of VDC Ca2+ channels in the trachea of
      ITK-/- mice. Taken together, these results suggest that the presence of ITK may
      play a modulating role in the pharmacomechanical as well as in the
      electromechanical coupling of airway smooth muscle contraction.

PMID- 15477127
TI  - IPL576,092, a novel anti-inflammatory compound, inhibits leukocyte infiltration
      and changes in lung function in response to allergen challenge.
AB  - IPL576,092, a lead compound from a novel class of polyhydroxylated sterols, was
      tested in models of allergen-induced bronchoconstriction and airway inflammation.
      In a rat ovalbumin lung inflammation model, orally administered IPL576,092
      significantly inhibited the challenge-mediated increase in total bronchoalveolar
      lavage leukocyte numbers, and macrophage and lymphocyte infiltration (1-10
      mg/kg/day). There was a similar trend towards inhibition of eosinophil and
      neutrophil accumulation. Sheep were treated with IPL576,092 by inhalation (400
      microg/kg/day), and lung resistance and airway hyper-responsiveness (AHR) were
      determined after Ascaris suum challenge. IPL576,092 significantly reduced the
      early and late phase bronchoconstrictor responses by 63+/-4.6 and 84+/-4.6%,
      respectively. IPL576,092 also blocked AHR (2.2+/-5.7% change from pre-challenge
      PC400), whereas control animals showed a 62.2+/-2.6% decrease in the PC400
      (p<0.05). Oral IPL576,092 (5 mg/kg/day) also significantly decreased hyper
      reactivity in mice. In a guinea pig model, IPL576,092 (5 mg/kg/day) significantly
      protected against allergen-induced increases in lung resistance (11.4+/-2.3
      control versus 4.8+/-01.5 IPL576,092, area under the curve) and inhibited the
      increase in lung elastance (280+/-58 control versus 167+/-52 IPL576,092, p<0.05).
      IPL576,092, unlike dexamethasone, did not significantly decrease rat serum
      corticosterone levels or thymus and spleen weights, supporting a mechanism of
      action different from classic glucocorticoids. IPL576,092 significantly
      attenuates characteristics of an asthmatic response, indicating therapeutic
      potential for this drug class.

PMID- 15477128
TI  - N-brain natriuretic peptide: correlation with tricuspid insufficiency in Gaucher
      disease.
AB  - NT-pro-brain natriuretic peptide (NT-proBNP) values are correlated with right
      ventricle dysfunction in pulmonary hypertension and have been recommended as a
      prognostic marker for symptomatic primary pulmonary hypertension. The purpose of
      this pilot study was to determine whether NT-proBNP values correlate with mild to
      moderate pulmonary hypertension in Gaucher disease. The NT-proBNP assay was
      performed on sera from patients with type I (non-neuronopathic) Gaucher disease
      who were known to have tricuspid insufficiency (TI) gradient values on
      echocardiography that were normal (TI<20 mmHg), borderline (TI=25-29 mmHg), or
      abnormal (TI>or= 30 mmHg) over time. There was a statistically significant
      correlation (p=0.05) between mean NT-proBNP values and TI gradient group: mean NT
      proBNP for normal TI gradient (n=20 patients)=133.3 (range: 46-445)pg/ml; mean NT
      proBNP for borderline TI gradient (n=17 patients)=288.7 (range: 81-1088)pg/ml;
      and mean NT-proBNP for elevated TI gradient (n=10 patients)=1034.2 (73
      6703)pg/ml. Treatment status was not correlated with TI gradient or NT-proBNP
      values. Thus, in this pilot study of Gaucher disease that included patients with
      mild to moderate pulmonary hypertension, NT-proBNP was correlated with
      echocardiographic findings. Further studies will be required to ascertain if NT
      proBNP can be used for diagnosis and monitoring of these patients.

PMID- 15477129
TI  - The infrared vibrational intensities and polar tensors of HFCO and DFCO.
AB  - The infrared vibrational intensities of HFCO and DFCO have been calculated at the
      B3LYP/cc-pVTZ, MP2(FC)/6-311++G(3d,3p) and QCISD(FU)/aug-cc-pVTZ levels. All
      calculations predict the isotopomers to have identical intensity sums, within
      about 1 km mol(-1). This is in contrast with experimental intensity sum results
      reported in the literature. Dipole moment derivative directions calculated by the
      three methods are in excellent agreement for all in-plane normal coordinates. All
      the theoretical polar tensor elements are also in good agreement with each other
      having standard deviations varying between 0.003 and 0.043 e. The oxygen and
      fluorine atoms have negative mean derivatives (approximately -0.6 e), whereas the
      carbon mean derivative is very positive (approximately +1.1e) and the hydrogen
      one is almost zero (approximately +0.03 e). The HFCO theoretical intensity sums
      calculated by all three methods as well as their carbon and oxygen mean dipole
      moment derivatives are in good agreement with those estimated from the
      experimental intensities and atomic mean derivatives of H2CO and F2CO.

PMID- 15477130
TI  - A UV resonance Raman (UVRR) spectroscopic study on the extractable compounds of
      Scots pine (Pinus sylvestris) wood. Part I: lipophilic compounds.
AB  - The wood resin in Scots pine (Pinus sylvestris) stemwood and branch wood were
      studied using UV resonance Raman (UVRR) spectroscopy. UVRR spectra of the sapwood
      and heartwood hexane extracts, solid wood samples and model compounds (six resin
      acids, three fatty acids, a fatty acid ester, sitosterol and sitosterol acetate)
      were collected using excitation wavelengths of 229, 244 and 257 nm. In addition,
      visible Raman spectra of the fatty and resin acids were recorded. Resin
      compositions of heartwood and sapwood hexane extracts were determined using gas
      chromatography. Raman signals of both conjugated and isolated double bonds of all
      the model compounds were resonance enhanced by UV excitation. The oleophilic
      structures showed strong bands in the region of 1660-1630 cm(-1). Distinct
      structures were enhanced depending on the excitation wavelength. The UVRR spectra
      of the hexane extracts showed characteristic bands for resin and fatty acids. It
      was possible to identify certain resin acids from the spectra. UV Raman spectra
      collected from the solid wood samples containing wood resin showed a band at
      approximately 1650 cm(-1) due to unsaturated resin components. The Raman signals
      from extractives in the resin rich branch wood sample gave even more strongly
      enhanced signals than the aromatic lignin.

PMID- 15477131
TI  - A UV resonance Raman (UVRR) spectroscopic study on the extractable compounds in
      Scots pine (Pinus sylvestris) wood. Part II. Hydrophilic compounds.
AB  - Hydrophilic extracts of Scots pine (Pinus sylvestris) heartwood and sapwood and a
      solid Scots pine knotwood sample were studied by UV resonance Raman spectroscopy
      (UVRRS). In addition, UVRR spectra of two hydrophilic model compounds (pinosylvin
      and chrysin) were analysed. UV Raman spectra were collected using 244 and 257 nm
      excitation wavelengths. The chemical composition of the acetone:water (95:5 v/v)
      extracts were also determined by gas chromatography. The aromatic and oleophilic
      structures of pinosylvin and chrysin showed three intense resonance enhanced
      bands in the spectral region of 1649-1548 cm(-1). Pinosylvin showed also a
      relatively intense band in the aromatic substitution region at 996 cm(-1). The
      spectra of the heartwood acetone:water extract showed many bands typical of
      pinosylvin. In addition, the extract included bands distinctive for resin and
      fatty acids. The sapwood acetone:water extract showed bands due to oleophilic
      structures at 1655-1650 cm(-1). The extract probably also contained oligomeric
      lignans because the UVRR spectra were in parts similar to that of guaiacyl
      lignin. The characteristic band of pinosylvin (996 cm(-1)) was detected in the
      UVRR spectrum of the resin rich knotwood. In addition, several other bands
      typical for wood resin were observed, which indicated that the wood resin in the
      knotwood was resonance enhanced even more than lignin.

PMID- 15477132
TI  - Design and applications of a home-built in situ FT-Raman spectroscopic cell.
AB  - In the field of heterogeneous catalysis, in situ spectroscopy is one of the
      topics with growing interest. The characterization of a catalyst under working
      conditions is essential to identify the catalytic active site and to study the
      relation between the surface structure of a catalyst and its catalytic
      performance. For the first time, the design of an in situ spectroscopic cell for
      FT-Raman is presented and its performance is demonstrated by monitoring the
      thermal conversion of as synthesized mesoporous titanium and by characterizing
      the molecular surface structure of the vanadium oxides grafted on MCM-48 after
      exposure to a probe molecule. The results in both cases indicate that the in situ
      FT-Raman cell is a promising technique for characterizing the molecular surface
      structure of catalyst materials.

PMID- 15477133
TI  - Infrared and laser Raman studies of bis(L-threoninium) sulphate monohydrate.
AB  - The infrared and Raman spectra of bis(L-threoninium) sulphate monohydrate crystal
      have been recorded and analysed at room temperature. The proposed assignment of
      normal modes is based on group theoretical analysis. There is extensive
      intermolecular hydrogen bonding in the crystal and this is responsible for the
      changes in the position and intensity of several bands. The anion fundamentals
      continue to be degenerated which indicates that its symmetry is unaffected in the
      molecule.

PMID- 15477134
TI  - Chlorobenzylidine-calf thymus DNA interaction II: circular dichroism and nuclear
      magnetic resonance studies.
AB  - The binding of chlorobenzylidine to calf thymus DNA has been studied in detail by
      means of circular dichroism (CD), nuclear magnetic resonance (1H NMR),
      viscosimetry and denaturation temperature (Tm). Chlorobenzylidine is found to
      intercalate between base pairs of DNA as evidence by: (1) induced circular
      dichroism; (2) broadened 1H NMR signals; (3) enhanced viscosity; and (4)
      increased denaturation temperature of the DNA helix. In addition, Scatchard plot
      from CD titration data gives a binding constant of 2.6 x 10(4) M(-1) and a
      binding site size of 4 base pairs at 25 degrees C. Matrix rank analysis shows
      that there are three main components contributing to the observed CD spectra. The
      nuclear magnetic resonance experiment shows that the planar aromatic ring of
      tetrahydroberberine group in chlorobenzylidine intercalates between the base
      pairs of DNA when chlorobenzylidine is bound to DNA.

PMID- 15477135
TI  - Experimental and computational studies of the structure and vibrational spectra
      of aminomethyl-dimethyl-phosphine oxide and its 15N labeled isomer.
AB  - Infrared (4000-100 cm(-1)) spectra of aminomethyl-dimethyl-phosphine oxide and
      15N-aminomethyl-dimethyl-phosphine oxide have been measured. Geometric parameters
      (bond distances and angles), net electronic charges and vibrational spectroscopic
      data of both compounds calculated at various levels of theory (B3LYP/6-31G* and
      Moeller-Plesset perturbational theory (MP2)/6-31G*) are reported. The theoretical
      spectral results are discussed mainly in terms of comparison with infrared (4000
      100 cm(-1)) spectral data. Better coincidence was achieved with the frequencies
      calculated at the MP2/6-31G* level: the standard deviation is 16 cm(-1). The
      calculated isotopic frequency shifts, induced by the 15N labeling, are in good
      accordance with the measured ones. Complete vibrational assignment is made with
      the help of MP2 force field calculations. Data obtained here are used to reassign
      some of the vibrational frequencies.

PMID- 15477136
TI  - Vibrational spectroscopy of stichtite.
AB  - Raman spectroscopy complimented with infrared spectroscopy has been used to study
      the mineral stitchtite, a hydrotalcite of formula Mg6Cr2(CO3)(OH)16.4H2O. Two
      bands are observed at 1087 and 1067 cm(-1) with an intensity ratio of
      approximately 2.5/1 and are attributed to the symmetric stretching vibrations of
      the carbonate anion. The observation of two bands is attributed to two species of
      carbonate in the interlayer, namely weakly hydrogen bonded and strongly hydrogen
      bonded. Two infrared bands are found at 1457 and 1381 cm(-1) and are assigned to
      the antisymmetric stretching modes. These bands were not observed in the Raman
      spectrum. Two infrared bands are observed at 744 and 685 cm(-1) and are assigned
      to the nu4 bending modes. Two Raman bands were observed at 539 and 531 cm(-1)
      attributed to the nu2 bending modes. Importantly the band positions of the
      paragenically related hydrotalcites stitchtite, iowaite, pyroaurite and reevesite
      all of which contain the carbonate anion occur at different wavenumbers.
      Consequently, Raman spectroscopy can be used to distinguish these minerals,
      particularly in the field where many of these hydrotalcites occur simultaneously
      in ore zones.

PMID- 15477137
TI  - Spectrophotometric determination of ampicillin sodium in pharmaceutical products
      using sodium 1,2-naphthoquinone-4-sulfonic as the chromogentic reagent.
AB  - Spectrophotometric determination of ampicillin sodium is described. The
      ampicillin sodium reacts with sodium 1,2-naphthoquinone-4-sulfonic in pH 9.00
      buffer solution to form a salmon pink compound, and its maximum absorption
      wavelength is at 463 nm, epsilon463 = 1.14 x 10(4). The absorbance of ampicillin
      sodium from 2.0-80 microg ml(-1) obeys Beer's law. The linear regression equation
      of the calibration graph is C = 40.24A - 2.603, with a linear regression
      correlation coefficient is 0.9997, the detection limit is 1.5 microg ml(-1),
      recovery is from 97.23 to 104.5%. Effects of pH, surfactant, organic solvents,
      and foreign ions on the determination of ampicillin sodium have been examined.
      This method is rapid and simple, and can be used for the determination of
      ampicillin sodium in the injection solution of ampicillin sodium. The results
      obtained by this method agreed with those by the official method (HPLC).

PMID- 15477138
TI  - Relationship between force constants and bond lengths for CX (X = C, Si, Ge, N,
      P, As, O, S, Se, F, Cl and Br) single and multiple bonds: formulation of Badger's
      rule for universal use.
AB  - Geometries and harmonic vibrational wave numbers were calculated on a series of
      simple compounds that contain the atoms of elements in the groups 14-17 by
      density functional theory at the B3LYP/6-311++G(3df,2pd) level. The calculated
      wave numbers agree well with the observed harmonic wave numbers with
      substantially the same accuracy for the compounds of the different groups. The
      stretching force constants of the CX (X = C, Si, Ge, N, P, As, O, S, Se, F, Cl
      and Br) single and multiple bonds were obtained. The CX stretching force
      constants increase with a decrease of the bond lengths as the element X in the
      same period goes from left to right in the periodic table. The individual
      intrinsic properties of the CX bonds are lost gradually with increasing the
      period of the element X. The unified interpretation of Badger's rule has enabled
      the formulation of a common equation for universal use f = 2.8 R(-3) to relate
      the force constants f (10(2) N m(-1)) and the reduced bond lengths R (10(-10) m).

PMID- 15477139
TI  - Effects of chloride introduction on up-conversion luminescence in Tm3+ -doped
      tellurite glasses.
AB  - Blue up-conversion luminescence properties in Tm3+ -doped lead chloride tellurite
      glasses have been studied under 980 nm excitation. The intense blue and
      relatively weak red emissions centered at 476 and 649 nm corresponding to the
      transitions 1G4 --> 3H6 and 1G4 --> 3H4 of Tm3+, respectively, are simultaneously
      observed at room temperature. The effect of PbCl2 on up-conversion intensity is
      observed and discussed, and possible up-conversion mechanisms are evaluated. The
      intense blue up-conversion luminescence of Tm3+ -doped lead chloride tellurite
      glasses may be a potentially useful material for developing up-conversion optical
      devices.

PMID- 15477140
TI  - Photophysical processes of a fluorene derivative containing 1,3,4-oxadiazole.
AB  - The photophysical processes of 9,9-bis[4'-[2''-phenyl-5''-(3'''-(methacryl
      amido)phenyl)]-1'',3'',4''-oxadiazolylphenyl]fluorene (F-MAOP) formed by Heck
      reaction of 9,9-bis(4'-iodophenyl)fluorene (F-IP) and 2-phenyl-5-[3'
      (methacrylamido)phenyl]-1,3,4-oxadiazole (OXD) have been carefully studied. The
      results show that the compound emits blue and blue-violet light and the emission
      spectra exhibit obvious solvent effect. With the increase of polarity of
      solvents, the fluorescence spectra change obviously and appear blue shift at room
      temperature. In addition, the light-emitting can be quenched by both electron
      donor (N,N-dimethylaniline, DMA) and electron acceptor (C60). When N,N
      dimethylaniline is gradually added into the solution of F-MAOP, the emission
      intensities of fluorescence are unusually increased. But when the concentration
      of DMA beyond a certain scope, the emission intensities of fluorescence are
      gradually decreased. The dimolecular exciplex between F-MAOP and C60 are formed
      and the quenching effect follows the Stern-Volmer equation. Moreover, interaction
      between F-MAOP and carbon nanotubes (CNTs) is also studied by fluorescent
      quenching.

PMID- 15477141
TI  - Highly sensitive detection of discrete absorption and B-type delayed fluorescence
      of dibenzanthracene in PMMA.
AB  - High resolution S0 --> Sn and T1 --> Tn electronic absorptions and B-type delayed
      fluorescence of 1,2,7,8-dibenzanthracene in polymethylmethacrylate (PMMA) were
      experimentally observed by flash and laser flash photolysis technique.
      Dibenzanthracene molecules were excited in a two-step process. In the first step,
      an excited singlet is created, which undergoes intersystem crossing to triplet
      state, then T-T absorption creates an excited triplet dibenzanthracene molecule,
      which returns to the first excited singlet level by intersystem crossing. The re
      created first excited singlet of dibenzanthracene decays back to the ground state
      by emitting B-type of delayed fluorescence, which was observed at the same
      emission band of prompt (normal) fluorescence, and R-, E-, P-types of delayed
      fluorescences. For normal fluorescence, S1 state is decaying to S0 ground state.
      For E- and P-type of delayed fluorescences, T1 state is decaying to S0 via S1
      state, and for B-type of delayed fluorescence, T2 state is decaying to S0 via S1
      state.

PMID- 15477142
TI  - Spectroscopic and electrochemical characterization of di-tert-butylated
      sterically hindered Schiff bases and their phenoxyl radicals.
AB  - A series of sterically hindered N-arylsalicylaldimines (SAs) previously prepared
      from substituted salicylaldehydes (X-Sal, where X = H, Cl, Br, NO2, OH, OCH3) and
      2,6-di-t-butyl-1-hydroxyaniline (LxH) and 2,5-di-t-butylaniline (Lx'H) were
      characterized by 1H and 13C NMR, UV-Vis and electrochemical methods. The
      electronic spectra (ES) (X = OH, OCH3) in alcoholic solvents (MeOH, EtOH, PrOH,
      iso-PrOH) unlike other solvents exhibit a new absorption band in the region 630
      675 nm (epsilon = 19-242 M(-1) cm(-1)), which are not characteristic for other SA
      known in literature. The ESR studies of primary phenoxyl radicals generated from
      LxH by their oxidation with PbO2 reveal that some of them with the time are
      converted to more stable secondary Coppinger's radical. The cyclic voltammograms
      of LxH and Lx'H except NO2-substituted ones in CH3CN are similar and along with
      two or three irreversible anodic waves at the potentials ranging from 0.0 to +1.9
      V versus Ag/AgCl, also display one or two irreversible reduction waves at
      potentials -0.6 to +0.5 V. A series of a new SA prepared from 3,5-di-t
      butylsalicylaldehyde and mono-substituted anilines (X = H, o-, p-F, Cl, Br, OCH3,
      p-t-butyl, 5,6-benzo) were characterized by analytical, spectroscopic (IR, UV
      Vis, 1H and 13C NMR), and electrochemical techniques. The ES spectra of o-, p-Cl,
      p-Br, o-CH3 and 5,6-benzo-substituted SA did not exhibit expected absorptions at
      400-500 nm in alcoholic solutions.

PMID- 15477143
TI  - Ab initio and DFT studies of the vibrational spectra of hydrogen-bonded
      PhOH...(H2O)4 complexes.
AB  - The vibrational characteristics (vibrational frequencies and infrared
      intensities) for the hydrogen-bonded complex of phenol with four water molecules
      PhOH...(H2O)4 (structure 4A) have been predicted using ab initio and DFT (B3LYP)
      calculations with 6-31G(d,p) basis set. The changes in the vibrational
      characteristics from free monomers to a complex have been calculated. The ab
      initio and B3LYP calculations show that the observed four intense bands at 3299,
      3341, 3386 and 3430 cm(-1) can be assigned to the hydrogen-bonded OH stretching
      vibrations in the complex PhOH...(H2O)4 (4A). The complexation leads to very
      large red shifts of these vibrations and very strong increase in their IR
      intensity. The predicted red shifts for these vibrations with B3LYP/6-31G(d,p)
      calculations are in very good agreement with the experimentally observed. It was
      established that the phenolic OH stretching vibration is the most sensitive to
      the hydrogen bonding. The predicted red-shift with the B3LYP/6-31G(d,p)
      calculations for the most stable ring structure 4A (-590 cm(-1)) is in better
      agreement with the experimentally observed than the red-shift, predicted with
      SCF/6-31G(d,p) calculations. The magnitude of the wavenumber shift is indicative
      of relatively strong OH...H hydrogen-bonded interaction. The complexation between
      phenol and four water molecules leads to strong increase of the IR intensity of
      the phenolic OH stretching vibration (up to 38 times).

PMID- 15477144
TI  - Spectroscopic studies of complexes of iodine with the bases 1-aza-15-crown-5 and
      3,6,9,14-tetrathiabicyclo[9.2.1]tetradeca-11,13-diene.
AB  - The interactions of iodine with each of the electron donors 1-aza-15-crown-5 (AC)
      and 3,6,9,14-tetrathiabicyclo[9.2.1]tetradeca-11,13-diene (TTBCTD) in CHCl3 have
      been described in terms of 1:1 and 1:2, base: I2 complexes, respectively, forming
      the complexes of the type [(AC)2I]+.I3- and [(TTBCTD)(I2)2]. The [(AC)2I]+.I3-
      shows the characteristic absorptions of I3- ion at 265 and 365 nm while the
      charge-transfer transition of [(TTBCTD)(I2)2] occurs at 320 nm. The formation of
      the two complexes was further confirmed by far infrared measurements. The values
      of the complex formation constant, K, and the absorpativity, in CHCl3 are
      calculated for the complex [(AC)2I]+.I3-.

PMID- 15477145
TI  - Vibrational frequencies and structural determination of trimethylarsine oxide.
AB  - The normal mode frequencies and corresponding vibrational assignments of
      trimethylarsine oxide are examined theoretically using the Gaussian 98 set of
      quantum chemistry codes. All normal modes were successfully assigned to one of
      eight types of motion (As-C stretch, As=O stretch, C-H stretch, C-As-C bend, As=O
      bend, H-C-H bend, CH3 wag, and CH3 twist) utilizing the C3v symmetry of the
      molecule. Calculations were performed at the Hartree-Fock, DFT(B3LYP), and MP2
      levels of theory using the standard 6-311G** basis. Calculated infrared
      intensities and Raman activities are reported.

PMID- 15477146
TI  - A spectroscopic study on defluorination of poly(tetrafluoroethylene) by
      alkyllithium/electron-donating solvents.
AB  - Defluorination of PTFE by alkyllithium/electron-donating solvents such as
      N,N,N',N'-tetramethylethylenediamine (TMEDA), hexamethylphosphoramide (HMPA) was
      studied by means of spectroscopy such as ESR, 7Li- and 13C-NMR, XPS, UV-Vis and
      IR. Based on the experimental results, it was concluded that an electron from
      radical species, which was generated in the alkyllithium/electron-donating
      solvent, was transferred onto PTFE molecule so as to eliminate fluorine atoms
      from the PTFE and to form carbon-centered radicals on the PTFE; concomitantly,
      the alkyl group of the alkyllithium was transferred onto the PTFE. Combined with
      the experimental results of the phenyllithium/HMPA system, mechanism of the
      fluorine atom elimination reactions from PTFE by the radical species is
      discussed.

PMID- 15477147
TI  - Mass, IR, electronic and EPR spectral studies on transition metal complexes with
      a new tetradentate 12-membered new macrocyclic ligand.
AB  - Complexes of Cr(III), Co(II), Ni(II) and Cu(II) containing a novel macrocyclic
      tetradentate nitrogen donor (N4) ligand prepared via reaction of 2,3-hexanedione
      and ethylenediamine has been prepared and characterized. The newly synthesized
      ligand (L) and its complexes have been characterized on the basis of elemental
      analysis, molar conductance, magnetic moment susceptibility, EI-Mass, IR,
      Electronic and EPR spectral studies. The complexes are of high-spin type and four
      coordinated tetrahedral, five coordinated square pyramidal and six coordinated
      octahedral/tetragonal geometries. The ligand (L) and its soluble transition metal
      complexes have also been screened against different bacteria and plant pathogenic
      fungi in vitro.

PMID- 15477148
TI  - Triphenyl phosphine adducts of platinum(IV) and palladium(II) dithiocarbamates
      complexes: a spectral and in vitro study.
AB  - Triphenyl phosphine adducts of dithiocarbamate complexes of platinum(IV) and
      palladium(II) of the type [Pt(L)2PPh3Cl2] and [Pd(L)2PPh3] [L: morpholine
      dithiocarbamate (L1), aniline dithiocarbamate (L2) and N-(methyl, cyclohexyl)
      dithiocarbamate (L3)] were prepared and characterized by elemental analysis,
      electronic, IR, 1H NMR and 13C NMR spectral studies. Thermal studies of the
      complexes were carried out. In vitro antitumor activity has been screened towards
      human adenocarcinoma cell lines and showed significant inhibition even at very
      low concentration.

PMID- 15477149
TI  - Spectroscopic studies on Co(II) and Cu(II) complexes of 6-amino-1-methyl-5
      nitrosouracil and its 6-methylamine derivative.
AB  - Four complexes are obtained during the reactions of 6-amino-1-methyl-5
      nitrosouracil and its 6-methylamine derivative with Co(II) and Cu(II) ions.
      Theses complexes were characterized through their elemental, thermal analysis,
      infrared and 1H NMR spectroscopes. The obtained results indicate that, the
      exocyclic oxygen and nitrogen atoms are the most probable binding sites rather
      than ring nitrogen atoms. For cobalt complexes, the two pyrimidine bases act as
      bidentate ligands in the anionic form with the dissociation of iminic or N3
      proton depending upon the nature of substituents on the pyrimidine ring. For
      copper complexes, the pyrimidine bases interact in the neutral form as
      monodentate ligands. Octahedral geometries are proposed for all of these
      complexes.

PMID- 15477150
TI  - Optical absorption of 1H-pyrazolo[3,4-b]quinoline and its derivatives.
AB  - The results of experimental studies and quantum chemical simulations of the
      absorption spectra of 1H-pyrazolo[3,4-b]quinoline and its derivatives are
      presented. The quantum chemical calculations (semi-empirical AM1 and PM3 methods)
      show similarity in the absorption spectra of 1H-pyrazolo[3,4-b]quinoline and 1,3
      dimethyl-1H-pyrazolo[3,4-b]quinoline which are characterized by five strong
      absorption bands in the spectral range 200-500 nm. A substitution of the methyl
      groups by at least one phenyl group causes the drastic changes of the absorption
      spectra mainly within the spectral range 240-370 nm. We attribute these
      differences to additional molecular double bonding segments C=C of the
      substituted phenyl groups, i.e. to pi --> pi* transitions. A comparison of
      measured and the calculated absorption spectra manifests quite satisfactory
      agreement for all compounds in the part regarding the spectral position of the
      first oscillator (absorption threshold). At the same time, the measured spectra
      demonstrate the considerable broadening practically of all absorption bands and
      even complete damping some of them in the case of phenyl derivatives. The
      experiments performed with highly and weakly polar organic solvents shows that
      the solvent effect on the absorption spectra is small. For this reason the
      discrepancies between the calculated and the measured spectra are attributed to
      electron-vibronic coupling as well as to rotational dynamics of phenyl rings.

PMID- 15477151
TI  - Ethanol or/and captopril-induced precipitation and secondary conformational
      changes of human serum albumin.
AB  - We determined the secondary structure of solid-state native human serum albumin
      (HSA) and its precipitates induced by ethanol, captopril, or a captopril/ethanol
      mixture. A transmission Fourier transform infrared (FT-IR) microspectroscopy
      equipped with a thermal analyzer was used. The secondary structural composition
      of solid-state native HSA was 54% alpha-helices (1655 cm(-1)), 22% beta-turns
      (1679 cm(-1)), and 23% beta-sheets (1633 cm(-1)). After ethanol treatment, a new
      peak was observed at 1690 cm(-1), and the peak at 1633 cm(-1) was more apparent
      in the HSA precipitates. The corresponding compositions consisted of 59% alpha
      helices, 17% beta-turns, and 24% beta-sheets. After treatment with captopril with
      or without ethanol, the percentage of alpha-helices and beta-turns decreased in
      both HSA precipitates, but the percentage of beta-sheets increased. The
      temperature-dependent structural transformation from alpha-helices/random coils
      to beta-sheets for the solid-state HSA samples occurred at markedly different
      onset temperatures. The onset temperature for native HSA was 85 degrees C, and
      that for HSA precipitates obtained from ethanol, captopril, or captopril/ethanol
      was 100, 48 or 57 degrees C, respectively. The thermal-induced structural
      transformation from alpha-helices/random coils to beta-sheets implies a partial
      unfolding structure in these HSA samples.

PMID- 15477152
TI  - Spectra analysis of Nd(DBM)3(TPPO)2 in MMA solution and PMMA matrix.
AB  - The absorption spectra of Nd(DBM)3(TPPO)2 (DBM = dibenzoylmethane; TPPO =
      triphenylphosphine oxide) in methyl methacrylate (MMA) and polymethyl
      methacrylate (PMMA) were measured. Slater-Condon parameters (F2, F4, F6), Lander
      parameter (zeta4f), nephelauxetic effect parameters (beta, delta) and Judd-Ofelt
      parameters (Omega2, Omega4, Omega6) were calculated on the basis of the
      absorption spectra. Analysis of the relationship between the structure of rare
      earth complexes and the nephelauxetic effect, Judd-Ofelt parameter Omega2 was
      carried out. The radiative properties of Nd(DBM)3(TPPO)2 in PMMA were also
      predicted according to the Judd-Ofelt theory. The values of the radiative
      lifetime and the emission cross-section of 4F3/2 --> 4I11/2 fluorescence
      transition are comparable with those shown by glasses used in the solid-state
      laser applications.

PMID- 15477153
TI  - Solvent effect on infrared spectra of methyl methacrylate in CCl4/C6H14,
      CHCl3/C6H14 and C2H5OH/C6H14 binary solvent systems.
AB  - Research of methyl methacrylate (MMA) in three kinds of binary solvent systems
      (CCl4/C6H14, CHCl3/C6H14 and C2H5OH/C6H14) on the infrared (IR) spectra was
      reported. Two types of carbonyl stretching vibration bands for MMA in CHCl3/C6H14
      or C2H5OH/C6H14 mixtures were found with the changing of the mole fraction of
      CHCl3 (XCHCl3) or C2H5OH (XC2H5OH). The carbonyl stretching vibration bands at
      lower frequencies in the above two mixtures were attributed to the formation of
      hydrogen bonding between MMA and CHCl3 or C2H5OH. While in CCl4/C6H14 mixtures
      there was only one type of carbonyl stretching vibration band of MMA. Good linear
      correlations between the frequencies of C=O or C=C stretching vibration band of
      MMA and XCCl4, XCHCl3 or XC2H5OH were found, respectively. The solute-solvent
      interactions in the three different binary solvent systems were discussed in
      detail.

PMID- 15477154
TI  - Raman spectroscopic analysis of supersaturated aqueous solution of MgO.B2O3
      32%MgCl2-H2O during acidification and dilution.
AB  - Raman spectra of supersaturated aqueous solution of MgO.B2O3-32%MgCl2-H2O during
      acidification/alkalization and dilution have been studied. The assignments of the
      recorded Raman shift are given. The main existing forms of polyborate anions and
      their interaction in borate aqueous solution have been proposed through
      spectroscopic analysis. The experimental results indicate that the higher
      concentration of cation are beneficial not only to the dissolution of boric acid
      but also to the polymerization of polyborate anions. The existing forms and
      interaction among them also depend on the concentration of boron and the pH value
      in solution.

PMID- 15477155
TI  - Development of a novel fluorescent probe for nitric oxide detection: 8-(3',4'
      diaminophenyl)-difluoroboradiaza-S-indacence.
AB  - A novel fluorescent probe, 8-(3',4'-diaminophenyl)-difluoroboradiaza-S-indacence
      (DABODIPY), was designed and synthesized for monitoring nitric oxide production,
      which features high photostability and no pH dependency over a wide pH range. The
      fluorescence of 8-(3',4'-diaminophenyl)-difluoroboradiaza-S-indacence is very
      low, however, when the probe traps nitric oxide (NO) in the presence of dioxygen,
      the strong fluorescent triazole form is obtained, which offers the advantages of
      specificity, and sensitivity for direct detection of NO. Calibration using
      various concentrations of NO showed the method has good linearity (0.08-4.00
      micromol l(-1)) and its detection limit is 10 nmol l(-1) (s/n = 3). The proposed
      method has been used to monitor the release of NO from S-nitrosocysteine, a NO
      releasing agent.

PMID- 15477156
TI  - Effects of pressure and solvents on the infrared absorption intensity of the O-H
      stretching mode of phenol in solutions.
AB  - Effects of pressure and solvents on the infrared spectrum of phenol in solutions
      have been investigated using a hydrostatic high-pressure cell with synthetic
      diamond windows. For the first time, we performed a quantitative investigation of
      the effect of pressure on the absolute intensity of O-H stretching mode up to 150
      MPa (in CCl4) and 200 MPa (in CS2). For comparison, we measured the effect of
      solvents on the absorption intensity. The Polo-Wilson theory, which is the most
      traditional theory for medium effects on the intensity, was tested for present
      results. The pressure dependence was in sufficient agreement with their formula,
      while the solvent dependence is unsatisfactory. This suggests that the
      traditional intensity correction by Polo-Wilson's formula is practically valid
      for pressure-tuning infrared experiments.

PMID- 15477157
TI  - Synthesis, investigation and spectroscopic characterization of piroxicam ternary
      complexes of Fe(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) with glycine and
      DL-phenylalanine.
AB  - The ternary piroxicam (Pir; 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine
      3-carboxamide 1,1-dioxide) complexes of Fe(II), Fe(III), Co(II), Ni(II), Cu(II)
      and Zn(II) with various amino acids (AA) such as glycine (Gly) or DL
      phenylalanine (PhA) were prepared and characterized by elemental analyses, molar
      conductance, IR, UV-Vis, magnetic moment, diffuse reflectance and X-ray powder
      diffraction. The UV-Vis spectra of Pir and the effect of metal chelation on the
      different interligand transitions are discussed in detailed manner. IR and UV-Vis
      spectra confirm that Pir behaves as a neutral bidentate ligand coordinated to the
      metal ions via the pyridine-N and carbonyl group of the amide moiety. Gly
      molecule acted as a uninegatively monodentate ligand and coordinate to the metal
      ions through its carboxylic group, in addition PhA acted as a uninegatively
      bidentate ligand and coordinate to the metal ions through its carboxylic and
      amino groups. All the chelates have octahedral geometrical structures while
      Cu(II)- and Zn(II)-ternary chelates with PhA have square planar geometrical
      structures. The molar conductance data reveal that most of these chelates are non
      electrolytes, while Fe(III)-Pir-Gly, Co(II)-, Ni(II)-, Cu(II)- and Zn(II)-Pir-PhA
      chelates were 1:1 electrolytes. X-ray powder diffraction is used as a new tool to
      estimate the crystallinity of chelates as well as to elucidate their geometrical
      structures.

PMID- 15477158
TI  - Solvatochromic behavior of the electronic absorption spectra of some azo
      derivatives of amino pyridines.
AB  - The electronic absorption spectra of a series of the entitled eight compounds
      containing groups with variable electronic characters were recorded. The solvents
      were selected to cover a wide range of parameters (refractive index, dielectric
      constant and hydrogen bonding capacity). The electronic transitions are assigned
      and the solvent induced spectral shifts have been analyzed in relation to the
      different solute-solvent interaction mechanisms using computational chemistry.
      The regression analysis is applied for correlation parameters. The phenomenon of
      tautomerism is explained. The electronic character of the substituent as well as
      the chemistry of the solvent are the major factors for the solvatochromic
      behavior.

PMID- 15477159
TI  - Effect of TiO2 on electron paramagnetic resonance, optical transmission and dc
      conductivity of vanadyl doped sodium borate glasses.
AB  - Glass systems with composition xTiO2.(30 - x)Na2O.70B2O3 (series I) and xTiO2.(70
      - x)B2O3.30Na2O (series II) containing 2 mol% V2O5 have been prepared (0 < or = x
      < or = 7, mol%) by normal melt-quenching. The electron paramagnetic resonance
      (EPR) spectra of VO2+ ions have been recorded in the X-band (approximately 9.13
      GHz) at room temperature. Spin Hamiltonian parameters, gparallel, gperpendicular,
      Aparallel, Aperpendicular, the dipolar hyperfine coupling parameter (P) and the
      Fermi contact interaction parameter (K) have been calculated. The increase in
      Deltagparallel/Deltagperpendicular with increase in TiO2 content in series I
      shows that the octahedral symmetry of V4+O6 complex is reduced, whereas in series
      II the octahedral symmetry is improved with increase in x. The decrease in P, in
      both the series, indicates that the 3dxy orbit expands with increase in mol% of
      TiO2. The molecular orbital coefficients, alpha2 and gamma2 have been calculated
      by recording the optical transmission spectra in the range 500-850 nm. alpha2 and
      gamma2 increase with increase in x in both the series, which indicates that, the
      covalency of the vanadium oxygen bonds decreases. The dc conductivity sigma,
      decreases and activation energy, W increases with increase in TiO2:Na2O ratio
      whereas with increase in TiO2:B2O3 ratio the variation in sigma and W is within
      experimental error.

PMID- 15477160
TI  - Investigations of the optical spectra and EPR parameters in CaWO4:Yb3+.
AB  - In this paper, we calculate the optical spectra data (crystal-field energy
      levels), the electron paramagnetic resonance (EPR) g factors gparallel,
      gperpendicular of Yb3+ and hyperfine structure constants Aparallel,
      Aperpendicular of 171Yb3+ and 173Yb3+ isotopes in CaWO4 crystal in a unified way
      from the crystal-field theory. All the calculated results are in good agreement
      with the experimental values. The signs of Aparallel and Aperpendicular for both
      isotopes 171Yb3+ and 173Yb3+ are suggested.

PMID- 15477161
TI  - Fluorescence quenching method for the determination of sodium dodecyl sulphate
      with near-infrared hydrophobic dye in the presence of Triton X-100.
AB  - A fluorophotometric method for the determination of anionic surfactant sodium
      dodecyl sulphate (SDS) was proposed. The method is based on the quenching effect
      of SDS on the fluorescence of near-infrared (NIR) hydrophobic dye, 2-[4'chloro
      7'(3''hexadecyl-2''benzothiazolinylidene)-3',5'-(1''',3'''-propanediyl)-1',3',5'
      heptatriene-1'-yl]-3-ethylbenzothiazolium iodide (dye I) in the presence of
      Triton X-100. The calibration graph is linear in the concentration range from 0
      to 2 x 10(-6) mol L(-1) of SDS with a detection limit (LOD) of 8.3 x 10(-8) mol
      L(-1). The relative standard deviation for the determination of 7 x 10(-7) mol L(
      1) SDS was 4.1%. Recoveries of 95.3-110.3% were found for the addition to 1.0 x
      10(-6) mol L(-1) SDS in the analysis of environmental water samples. Preliminary
      research shows that the fluorescence quenching is due to the formation of dye
      aggregate facilitated by SDS.

PMID- 15477162
TI  - Electronic, infrared and Raman spectral studies on the molecular complex of N,N'
      dibenzyl-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane with iodine.
AB  - The molecular complexation reaction between iodine and the interesting mixed
      oxygen-nitrogen cyclic base N,N'-dibenzyl-1,4,10,13-tetraoxa-7,16
      diazacyclooctadecane (DBTODAOD) has been studied spectrophotometrically in
      CH2Cl2, CHCl3, and CCl4. The results of photometric titrations and elemental
      analysis show that the DBTODAOD base:iodine ratio is 1:4 forming the heptaiodide
      complex [(DBTODAOD)I]+.I7-. The heptaiodide ion (I7-) is described as I3-(2I2)
      confirmed by the observation of its characteristic strong absorptions around 365
      and 295 nm. In addition, the far infrared spectrum of the solid complex shows the
      three vibrations of I3- unit at 142, 104, and 62 cm(-1) assigned to nuas(I-I),
      nus(I-I) and delta(I-3), respectively, while the Raman spectrum shows the
      corresponding bands at 147 and 108 cm(-1) beside two other bands at 181 and 214
      cm(-1) related to the vibration of the I2 unit and the first overtone of nus(I-I)
      of I3-, respectively. The structure of the formed heptaiodide complex was further
      supported by thermal gravimetric analysis measurements. Group theoretical
      analysis indicate that the triiodide unit (I3-) in I7- may be non-linear with C2v
      symmetry.

PMID- 15477163
TI  - Ab initio and density functional theory studies on vibrational spectra of
      palladium (II) and platinum (II) complexes of methionine and histidine: effect of
      theoretical methods and basis sets.
AB  - The vibrational spectra of methionine and histidine-containing palladium (II) and
      platinum (II) complexes, cis-M(Met)X2 and cis-M(His)X2 (M = Pd and Pt; X = F, Cl,
      Br and I; Met = methionine, His = histidine), have been systematically
      investigated by ab initio Restricted Hartree-Fock (RHF) and density functional
      B3LYP methods with LanL2DZ and SDD basis sets. The geometries of cis-Pd(Met)Cl2,
      cis-Pt(Met)Cl2, cis-Pd(His)Cl2 and cis-Pt(His)I2 optimized and vibrational
      frequencies and IR intensities of cis-M(Met)Cl2 and cis-M(His)Cl2 (M = Pd and Pt)
      calculated are evaluated via comparison with the experimental values. The
      vibrational frequencies calculated show that the methods, rather than basis sets,
      affect the accuracy of the calculation. The best results that can reproduce the
      experimental ones are obtained at B3LYP level without any scale factor used. The
      vibrational frequencies of cis-M(Met)X2 and cis-M(His)X2 (M = Pd and Pt; X = F,
      Br and I) that have not yet been experimentally reported are predicted.

PMID- 15477164
TI  - Vibrational states of tetrahedral molecular species in electric fields. A
      theoretical model for quantitative description of the latent symmetry effects in
      vibrational spectroscopy of matrix isolated tetrahedral species.
AB  - A theoretical model that enables a quantitative description of latent symmetry
      effects in the case of matrix isolated tetrahedral species is developed. Several
      particular cases are considered, that are of special interest from vibrational
      spectroscopic viewpoint. It is shown that the observed appearances of the IR
      spectra of various XY4n- anions isomorphously isolated in solid matrices may be
      systematically explained in terms of the orientation of the effective local
      crystalline field vector. The model also principally enables calculation of the
      magnitude of the effective local homogeneous field vector as well as its
      direction with respect to the symmetry elements of the dopant species, and it can
      be successively corrected accounting for the field non-homogeneity. Also, a solid
      theoretical basis is for the first time presented for the significantly smaller
      site group splitting of the nu4 modes of dopant XY4n- species in comparison to
      the splitting of nu3 ones, which is often observed in the IR spectra. However,
      the presented approach has potentially a much wider applicability, as it in facts
      considers the vibrational states of tetrahedral molecular species in electric
      fields, which may be of a different origin, for example, electrodes in
      electrochemical systems, external fields in Stark-type spectroscopies, etc.

PMID- 15477165
TI  - Photophysical studies of 9,10-phenanthrenequinones.
AB  - The characterization of the excited states of 9,10-phenanthrenequinone (PQ) and
      its derivatives substituted in the 3 and 6 positions with methoxy (PQ1), chloro
      (PQ2), methyl (PQ3) and fluoro (PQ3) was carried out using steady-state UV
      Visible absorption spectroscopy and phosphorescence emission spectroscopy at room
      temperature and at 77 K. Nanosecond laser flash photolysis was used to obtain the
      time resolved spectra from the triplet emission decays. The compounds presented
      phosphorescence in benzene, chlorobenzene and acetonitrile solutions at room
      temperature and at 77 K. The phosphorescence of the methoxy derivative, however,
      was observed only at low temperature. The derivatives showed a slightly higher
      triplet energy than PQ. The Hammett plots were applied to correlate singlet and
      triplet energies with sigma values that account for resonance and the radical
      character. It is observed that singlet and triplet energies increase with
      electron donating groups.

PMID- 15477166
TI  - Theoretical study of the external heavy atom effect on phosphorescence of free
      base porphin molecule.
AB  - The radiative lifetime of phosphorescence of free-base porphin (H2P) molecule and
      its complexes with noble-gas atoms are calculated by time-dependent density
      functions theory (TD DFT) with quadratic response functions for account of spin
      orbit coupling and electric dipole activity. The complexes with Ne, Ar, Kr, and
      Xe are used to simulate the external heavy atom (EHA) effect on phosphorescence
      of the H2P molecule in the corresponding noble gas matrices. The B3LYP functional
      and small basis set (3-21G) are used throughout the study and comparison of all
      complexes but other basis sets are also utilized to support the chosen approach.
      A slow radiative rate constant of free-base porphin phosphorescence (about 10(-3)
      s(-1)) is obtained with all basis sets being in the order of magnitude agreement
      with experimental estimations. A strong enhancement of the H2P phosphorescence
      rate (by 360 times) is calculated for Xe complex; while for Ne, Ar, and Kr
      complexes, the enhancement is equal to 1.1, 1.3, and 10.3 times, respectively. In
      these complexes, the noble gas atom is disposed at 3.6 A above the center of the
      porphin ring. In spite of shortcomings of the chosen simple model, the TD DFT
      calculations explain the most important features of the EHA effect on
      phosphorescence of free-base porphin. Calculations of the hyperfine coupling
      tensors for all magnetic nuclei in the lowest triplet state of H2P molecule and
      its complexes with noble-gas atoms indicate an appreciable penetration of the
      spin density to the EHA region. This can be connected with the enhancement of
      spin-orbit coupling in the H2P molecule.

PMID- 15477167
TI  - Matrix isolation infrared and ab initio study of the hydrogen bonding between
      formic acid and water.
AB  - The infrared spectra of the formic acid-water complexes isolated in argon
      matrices are reported. Both supersonic jet expansion and a conventional effusive
      source followed by trapping in solid argon at 10K are used to obtain the
      matrices. The experimental IR spectra are compared to the data obtained from high
      level ab initio (MP2) and DFT (B3LYP) calculations with 6-311++G(d,p) and aug-cc
      pVTZ basis sets. The complex formation results in red shifts in the C=O and O-H
      stretching vibrations and a blue shift in the C-O stretching vibration of formic
      acid. The O-H stretching modes of water also exhibit pronounced red shifts. Both
      the MP2 and B3LYP calculations located three minima corresponding to cyclic
      HCOOH...H2O complexes with two hydrogen bond interactions. The binding energies
      are -10.3, -5.1, and -3.5 kcal mol(-1), respectively, for the three complexes at
      the MP2/ aug-cc-pVTZ level, corrected for the basis set superposition error
      (BSSE) using the Boys-Bernardi counterpoise scheme. Comparison of the calculated
      frequencies of the three complexes with the matrix IR spectrum reveals that the
      lowest energy complex is formed. In addition, a complex of formic acid with two
      water molecules is observed.

PMID- 15477168
TI  - Influence of prenatal nicotine exposure on postnatal development of breathing
      pattern.
AB  - To determine if prenatal nicotine exposure alters the postnatal development of
      the ventilatory pattern and the frequency and duration of apneas, we recorded
      respiratory airflow with head-out body plethysmography in awake neonates on
      postnatal days 1, 2, 6, 10, 14, and 18. Data from 12 nicotine-exposed animals
      were compared with data from 12 saline-exposed animals. Nicotine (6 mg/kg of
      nicotine tartrate per day) or saline exposure was induced by osmotic minipumps
      that were implanted subdermally on the fifth day of gestation in Sprague-Dawley
      Dams. Although both saline- and nicotine-exposed pups gained weight at the same
      rate throughout the studies, there were subtle differences in ventilatory indices
      between the two groups. Nicotine-exposed animals had a significantly higher
      breathing frequency on day 10, and a lower tidal volume on days 14 and 18.
      Although ventilation tended to be lower in the nicotine-exposed animals, the
      difference was not significant. There was a significantly higher frequency of
      apneas in the nicotine-exposed compared with the saline-exposed animals on
      postnatal days 1 and 2, but the apnea duration did not differ between the groups.
      No apneas were observed in any of the animals after the sixth postnatal day.
      Prenatal nicotine exposure is associated with a greater incidence of apneas on
      the first two postnatal days, and then an altered breathing pattern that
      manifests at a later stage of development.

PMID- 15477169
TI  - Presence of lobeline-like sensations in exercising patients with left ventricular
      dysfunction.
AB  - Since there is evidence that lobeline-induced sensations, associated with
      discomfort in the mouth, throat and chest arise by stimulating juxtapulmonary or
      J receptors, we were interested in investigating if similar sensations are felt
      by patients with left ventricular dysfunction (LVD) in whom a natural stimulation
      of these receptors would occur by transient interstitial oedema or during
      augmentation of the stimulus, by increased pulmonary blood flow during exercise.
      Threshold doses of lobeline produced three or more respiratory sensations
      simultaneously in 9 out of 10 patients, which was greater than the response of
      the controls (P < 0.01). With mild exercise, a greater number of patients (7)
      than controls (1) reported feeling two or more sensations (P < 0.01); in fact
      half the controls did not express a respiratory sensation with equivalent
      exercise (P < 0.05). The predominant lobeline-like sensations reported by
      patients with exercise were a feeling of heat or burning and pressure in the
      throat or chest (P < 0.05). The presence of cough in three patients and in none
      of the controls was noteworthy. The mean latency with which sensations appeared
      during exercise in patients (4.4 +/- 0.3 min) was almost half that in controls
      (7.4 +/- 0.2 min) (P < 0.005). Since, respiratory sensations in response to
      lobeline and exercise were intensified in patients compared to controls and since
      both lobeline and exercise-induced sensations were similar (P < 0.05), we
      speculate that a common origin exists. Despite important caveats, that we
      discuss, in our view these respiratory sensations and cough arise from
      stimulation of J receptors.

PMID- 15477170
TI  - Respiratory responses to intermittent hypoxia in unsedated piglets: relation to
      substance P binding in brainstem.
AB  - Respiratory responses to single intermittent hypoxia (5 min 21% O(2), 5 min 8%
      O(2) X6) in 5-6, 10-11, 21-22 and 26-27 day-old piglets, and to recurrent six
      daily intermittent hypoxia in 10-11 and 26-27 day-old piglets were assessed.
      Substance P binding in the piglets' brainstem immediately after the last hypoxic
      episode was measured. All piglets hyperventilated during hypoxia. Weight adjusted
      inspired ventilation, tidal volume and instantaneous flow decreased with age. The
      oldest piglets uniquely displayed attenuated ventilation and tidal volume during
      the sixth versus first hypoxic episode with single intermittent hypoxia, and
      reduced inspired ventilation and tidal volume during the first hypoxic episode on
      the sixth daily hypoxia compared to single hypoxia. By contrast, substance P
      binding was greatly reduced in the solitary, hypoglossal, paraambigual and
      lateral reticular brainstem nuclei of both younger and older piglets following
      either single or recurrent intermittent hypoxia. Thus, the reduction in membrane
      bound neurokinin receptors by intermittent hypoxia, presumably consequent to
      endogenously released substance P, does not exclusively determine whether the
      ventilatory response to that hypoxia will be attenuated or not.

PMID- 15477171
TI  - Acute hypoxic ventilatory response and exercise-induced arterial hypoxemia in men
      and women.
AB  - Recent studies claim a higher prevalence of exercise-induced arterial hypoxemia
      (EIAH) in women relative to men and that diminished peripheral chemosensitivity
      is related to the degree of arterial desaturation during exercise in male
      endurance athletes. The purpose of this study was to determine the relationship
      between the acute ventilatory response to hypoxia (AHVR) and EIAH and the
      potential influence of gender in trained endurance cyclists and untrained
      individuals. Healthy untrained males (n = 9) and females (n = 9) and trained male
      (n = 11) and female (n = 10) cyclists performed an isocapnic AHVR test followed
      by an incremental cycle test to exhaustion. Oxyhemoglobin saturation (Sa(O(2))
      was lower in trained men (91.4 +/- 0.9%) and women (91.3 +/- 0.9%) compared to
      their untrained counterparts (94.4 +/- 0.8% versus 94.3 +/- 0.7%) (P < 0.05).
      AHVR and maximal O(2) consumption were related for all subjects (r = -0.46), men
      (r = -0.45) and women (r = -0.53) (P < 0.05) but AHVR was unrelated to Sa(O(2))
      for any groups (P > 0.05). We conclude that resting AHVR does not have a
      significant role in maintaining Sa(O(2)) during sea-level maximal cycle exercise
      in men or women.

PMID- 15477172
TI  - Time course of respiratory mechanics and pulmonary structural remodelling in
      acute lung injury.
AB  - The aim of this study was to evaluate the time course of in vivo and in vitro
      respiratory mechanics and examine whether these parameters could reflect the
      temporal changes in lung parenchyma remodelling in paraquat (PQ)-induced lung
      injury. Measurements were done 1, 3 and 8 weeks after the intraperitoneal (i.p.)
      injection of saline (control) or paraquat (7mgkg(-1)) in rats. Airway and tissue
      resistances increased from control in PQ1 and PQ3 and returned to control values
      in PQ8, in accordance with the magnitude of bronchoconstriction.
      Viscoelastic/inhomogeneous pressure, tissue elastance, the number of
      polymorphonuclear cells, and collagen fibre content in lung parenchyma increased
      in PQ1 and remained elevated in PQ3 and PQ8. Static elastance increased in PQ1,
      returned to control values after 3 weeks, and was correlated with the volume
      fraction of collapsed alveoli. In conclusion, there is a restoration of normal
      alveolar-capillary lung units with a gradual improvement in airway and tissue
      resistances and static elastance. However, the on-going fibrotic process kept
      elevated tissue elastance and viscoelastic/inhomogeneous pressure.

PMID- 15477173
TI  - Distribution of ventilation in young and elderly adults determined by electrical
      impedance tomography.
AB  - To determine the effect of age and posture on regional lung ventilation, eight
      young (26 +/- 1 years, mean +/- S.D.) and eight old (73 +/- 5 years) healthy men
      were studied by electrical impedance tomography in four body positions (sitting,
      supine, right and left lateral). The distribution of gas into the right and left
      lung regions was determined in the chest cross-section during tidal breathing at
      the resting lung volume, near residual volume and total lung capacity, as well as
      forced and slow vital capacity maneuvers. In the young, significant posture
      dependent changes in gas distribution occurred during resting tidal breathing
      whereas they were absent in the elderly. In the older subjects, the contribution
      of the right lung to global ventilation fell with the transition from sitting to
      supine posture during both full expiration maneuvers. During forced vital
      capacity, the high flow rate and early airway closure in the dependent lung,
      occurring at higher volumes in the elderly, minimized the posture-dependency in
      gas distribution which was present during the slow maneuver. Our study revealed
      the significant effect of age on posture-dependent changes in ventilation
      distribution.

PMID- 15477174
TI  - Mechanical properties of mouse distal lung: in vivo versus in vitro comparison.
AB  - While measurements of lung tissue mechanics have been made in several species,
      relatively little has been reported in the mouse. Moreover, whether in vivo
      measurements truly reflect tissue properties is somewhat controversial. We
      measured complex impedance of the mouse respiratory system in vivo using a
      ventilator, which applies a multiple frequency volume signal to the airway
      opening. A constant phase model was fit to the impedance data, yielding
      parameters for tissue damping (G) and elastance (H). Hysteresivity (eta) was
      calculated as G/H. Quasistatic pressure-volume (P-V) curves were obtained during
      deflation. In vitro measurements of complex impedance and stress-strain curves
      were made in lung tissue strips. Values of eta were significantly higher in vivo
      than in vitro (0.111 +/- 0.004 versus 0.042 +/- 0.003). The higher values of eta
      in vivo may represent the effects of airway heterogeneities, surfactant, or
      changes in alveolar geometry. Measurement of mechanics in the tissue strip offers
      a better assessment of pure tissue properties.

PMID- 15477175
TI  - Theoretical predictions of maximal oxygen consumption in hypoxia: effects of
      transport limitations.
AB  - A Krogh-type model for oxygen transport is used to predict maximal oxygen
      consumption (V(.-) O(2max)) of human skeletal muscle under hypoxic conditions.
      Assumed values of capillary density, blood flow, and hemoglobin concentration are
      based on measurements under normoxic and hypoxic exercise conditions. Arterial
      partial pressure of oxygen is assumed to decrease with reductions in inspired
      partial pressure of oxygen (P(I)O(2)), as observed experimentally. As a result of
      limitations of convective and diffusive oxygen delivery, predicted V(.-) O(2max)
      values decline gradually as P(I)O(2) is reduced from 150 mmHg to about 80 mmHg,
      and more rapidly as P(I)O(2) is further reduced. At very low levels of P(I)O(2),
      V(.-) O(2max) is limited primarily by convective oxygen supply. Experimentally
      observed values of V(.-) O(2max) in hypoxia show significant dispersion, with
      some values close to predicted levels and others substantially lower. These
      results suggest that maximal oxygen consumption rates in hypoxia are not
      necessarily determined by oxygen transport limitations and may instead reflect
      reduced muscle oxygen demand.

PMID- 15477176
TI  - Cognitive impairment associated with toxigenic fungal exposure: a replication and
      extension of previous findings.
AB  - In this study, neuropsychological data and symptom reports from 31 individuals
      exposed to toxic mold were examined. Most participants were found to have reduced
      cognitive functioning in multiple domains, with memory and executive functions
      the most commonly affected areas. Rates of dysfunction were significantly greater
      than chance on more than half of the tests. Number of cognitive impairments was
      found to be related to depression, although few neuropsychological test scores
      were correlated with depression. Results also indicated that symptom report of
      the mold-exposed participants was not significantly different from that of
      matched groups of 65 persons with mild traumatic brain injury (TBI) and 26
      individuals with moderate TBI. The mold-exposed participants reported
      significantly more symptoms than 47 people with no disability. This study adds to
      a growing body of literature (e.g., Baldo, Ahmad, & Ruff, 2002; Gordon,
      Johanning, & Haddad, 1999) relating exposure to mycotoxins to cognitive
      dysfunction.

PMID- 15477177
TI  - Construct validity of the 7/24 spatial recall test.
AB  - This investigation was conducted to examine the construct validity of the 7/24
      Spatial Recall Test (7/24). Participants were 64 outpatients who met criteria for
      clinically definite multiple sclerosis (MS). Data obtained from administration of
      a fixed neuropsychological assessment battery were analyzed to evaluate the
      relation between demographic, physical, and emotional factors and performance on
      the 7/24, to examine the measure's convergent/discriminant validity, to determine
      which variables account for the greatest proportion of variance in 7/24 scores,
      and to assess further the test's sensitivity to the cognitive sequelae of MS.
      Findings suggest that 7/24 scores are significantly explained by the constructs
      of visual-spatial perception/analysis, memory, reasoning, and/or processing
      speed. The proportion of variance in 7/24 performances accounted for by cognitive
      and demographic variables, however, was quite low. Relative to the measure's
      normative sample, participants in this investigation performed significantly
      poorer on number of responses recalled across Set A learning trials but not on
      Set A long-delay recall. Results of this investigation indicate some level of
      sensitivity of the 7/24 to the cognitive impairments associated with MS but offer
      only weak support for the 7/24 as a valid measure of visuospatial
      learning/memory.

PMID- 15477178
TI  - The persistent belief that VIQ-PIQ splits suggest lateralized brain damage.
AB  - There is a persistent belief in clinical psychology and neuropsychology that the
      Verbal IQ-Performance IQ (VIQ-PIQ) split can be used to reliably infer
      lateralized brain damage. We selected samples of patients with cleanly
      lateralized right (n = 23) or left (n = 26) hemisphere lesions and used Bayesian
      analyses to study the predictive validity of the Wechsler Adult Intelligence
      Scale-Revised VIQ-PIQ difference scores for identifying lateralized brain damage.
      The patients showed average VIQ-PIQ differences in the expected direction.
      However, on the basis of sensitivity, specificity, and positive predictive value
      statistics, we concluded that (a) the VIQ-PIQ split has no diagnostic predictive
      validity in persons with left hemisphere lesions (who are not aphasic) and (b)
      the VIQ-PIQ split has very limited diagnostic predictive validity in persons with
      right hemisphere lesions.

PMID- 15477179
TI  - Executive functioning and memory for the Rey-Osterreith complex figure task among
      community adolescents.
AB  - Although there is empirical support for the link between executive functioning
      (EF) and visual memory among adults, there has been less exploration of this link
      among children, especially adolescents. We examined the relation between several
      EF measures and performance on the Rey-Osterrieth Complex Figure (RCF) in a
      sample of 160 community adolescents. Each was administered the Wisconsin Card
      Sorting Test (WCST), Conners Continuous Performance Test (CPT), and the RCF,
      scored using Bernstein and Waber's (1996) Developmental Scoring System (DSS).
      Ability to organize the RCF related to memory encoding/retrieval, but not to long
      term storage. Indexes derived from the WCST and CPT failed to correlate with any
      RCF index, raising questions about the relation between DSS scores and EF. Even
      so, data supported the convergent validity of the DSS system as a reflection of
      visual-constructional ability and provided evidence of the importance of
      organizational strategies to visual memory among adolescents.

PMID- 15477180
TI  - A short version of the Hooper Visual Organization Test: reliability and validity.
AB  - Based on a detailed item analysis, Merten (2002) developed a 15-item short
      version of the Hooper Visual Organization Test (VOT) intended to resolve a number
      of shortcomings of the original scale. Problematic test items were eliminated,
      scoring rules were clarified, and new instructions and a graphic illustration of
      the task were introduced. This revision was aimed at reducing testing time by
      maintaining or even improving the scale's potential as a screener for
      visuospatial dysfunction. In this study, the short version was given for the
      first time "in its own right" to a sample of 153 neurological patients with a
      mean age of 60.0 years. Estimates of internal consistency for the resulting short
      form yielded acceptable results (.82 and .84). A retest analysis for a subsample
      of n = 72 at an interval of 2 to 3 days showed a mean increase in test scores of
      .6 points and a test-retest correlation of .93. Correlations with other test data
      are presented. The results indicate that the short version is comparable with the
      full scale in important psychometric aspects. With the elimination of a number of
      weak points, it may constitute a good substitute for the full VOT.

PMID- 15477181
TI  - Addressing the differences in speed of processing of the intervening calculation
      task on the modified Brown-Peterson task.
AB  - The Modified Brown-Peterson task (MBPT) is a task of divided attention and
      working memory that requires central executive functioning. It is a variant of
      the Brown-Peterson technique and is useful for studying short-term retention of
      information. It involves the recall of auditory information under conditions of
      interference (i.e., counting backwards). Previous research has not addressed the
      effect of individual differences in processing speed for the intervening
      calculations. In a sample of 81 young participants, we determined whether the
      number of correct calculations performed is related to recall performance on the
      MBPT. Results indicated that the number of calculations performed was not
      significantly related to the recall performance on the MBPT. Rather, the number
      of correct calculations performed during the interference task of the MBPT was
      associated with arithmetic ability as measured by the arithmetic subtest of the
      Adult Intelligence Scale-III (Wechsler, 1997). These results suggest that the
      subtractions in the MBPT create interference regardless of mathematical ability
      or speed at which the subtractions are performed during the interference
      condition of the MBPT task. This observation suggests that the results on this
      test are independent of mathematical ability and represent a useful measure of
      working memory.

PMID- 15477182
TI  - Sensation seeking and risk behaviors in young adults with and without a history
      of head injury.
AB  - Research has demonstrated a relation between sensation seeking and risky behavior
      as well as an association between risky behavior and the occurrence of head
      injury. This study assessed sensation seeking in young adults with and without a
      history of head injury by administration of the Sensation Seeking Scale (SSS),
      the Driver Risk Index (DRI), and the MacAndrews Scale of the Minnesota
      Multiphasic Personality Inventory (MMPI). There was a significant difference
      between the groups for the Thrill and Adventure Seeking Subscale of the SSS and
      the MacAndrews Scale of the MMPI, with head-injured participants scoring higher.
      Gender differences were seen in both groups for subscales of the SSS, with men
      scoring higher. Significant correlations were found for head-injured participants
      between the DRI and the Boredom Susceptiblity Subscale of the SSS, suggesting
      that as knowledge of risk increased for these participants, so did their
      preferences for risky behaviors. However, non-head-injured participants indicated
      a lower interest in risky behaviors as their knowledge of risk increased.

PMID- 15477184
TI  - Post traumatic stress, HIV and malaria: contemporary issues explored in depth.

PMID- 15477185
TI  - Mass trauma and mental health in Africa.

PMID- 15477186
TI  - Traumatic events and symptoms of post-traumatic stress disorder amongst Sudanese
      nationals, refugees and Ugandans in the West Nile.
AB  - OBJECTIVES: To compare the incidence of traumatic events and its association with
      symptoms of post-traumatic stress disorder in three population groups in northern
      Uganda and southern Sudan. METHODS: Household and individual level data collected
      through a single-round cross-sectional demographic survey. SETTING: The sub
      counties of Yivu, Odupi and Midia in the northern Ugandan district of Arua and of
      Otogo in Yei River district in southern Sudan. PARTICIPANTS: Residents of these
      Ugandan and Sudanese sub-counties were categorized on the basis of citizenship
      and refugee status (i.e. as Ugandan nationals, Sudanese nationals or Sudanese
      refugees). The random sample population consisted of 3,323 adults (mean age: 30
      years; 75% female) from 1,831 national and refugee households. RESULTS: Sudanese
      refugees reported the highest number of violent events experienced or witnessed
      ever and in the past one year . Witnessing of traumatic events, ever and in the
      past year , significantly predicted PTSD in surveyed population. Sex, age,
      education and occupation were also significantly associated with the development
      of PTSD symptoms. The population prevalence of PTSD was estimated to be 48% for
      Sudanese stayees, 46% for Sudanese refugees and 18% for Ugandan nationals.
      CONCLUSIONS: Symptoms of PTSD in war-affected Sudanese populations can be partly
      explained by traumatic event exposures. The high prevalence of violence and
      symptoms of PTSD in refugee populations highlight the need for better protection
      and security in refugee settlements. Humanitarian agencies must consider the
      provision of mental health services for populations affected by war and forced
      migration.

PMID- 15477187
TI  - Total lymphocyte count of 1200 is not a sensitive predictor of CD4 lymphocyte
      count among patients with HIV disease in Kampala, Uganda.
AB  - INTRODUCTION: Total Lymphocyte Count (TLC) has been found to be an inexpensive
      and useful marker for staging disease, predicting progression to AIDS and death
      and monitoring response to ART. However, the correlation between TLC and CD4 has
      not been consistent. Access to HAART is expanding in Kampala, Uganda, yet there
      are no published data evaluating the utility of TLC as inexpensive surrogate
      marker of CD4 cell count to help guide therapeutic decisions. OBJECTIVE: To
      evaluate clinical illnesses and total lymphocyte count (TLC) as surrogate markers
      of the CD4 cell count in HIV infected persons being considered for ART. METHODS:
      A total of 131 patients were enrolled and evaluated by clinical assessment, TLC
      and CD4 count. Clinical illnesses and TLC dichotomized at various cut-point
      values were used to determine the sensitivity, specificity, and positive and
      negative predictive values (PPV and NPV) for the diagnosis of CD4 count <200
      cells/mm 3 among 100 participants fulfilling criteria for WHO clinical stage 2
      and 3. RESULTS: A strong correlation was observed between TLC and CD4 (r = 0.73,
      p<0.0001). For all clinical syndromes, except pulmonary tuberculosis, the
      positive predictive values (PPV) for a CD4 count <200 cells/mm 3 were high (>80%)
      but the negative predictive values (NPV) were low. Using the WHO recommended TLC
      cut-off of 1200 cells/mm 3 to diagnose a CD4 less than 200 cells/mm 3 , the PPV
      was 100%, and the NPV was 32%. CONCLUSION: Our data showed a good correlation
      between TLC and CD4 cell count. However, the WHO recommended TLC cut-off of 1200
      did not identify the majority of WHO stage 2 and 3 patients with CD4 counts less
      than 200 cells/mm 3 . A more rational use of TLC counts is to treat all patients
      with WHO stage 2 and 3 who have a TLC <1200 and to limit CD4 counts to patients
      who are symptomatic but have TLC of >1200.

PMID- 15477188
TI  - "We have our own special language." Language, sexuality and HIV/AIDS: a case
      study of youth in an urban township in South Africa.
AB  - BACKGROUND: Despite the fact that most South African youth know about HIV/AIDS
      and how it can be prevented, there is a high prevalence of HIV/AIDS amongst youth
      in South Africa. Generally youth do not practice safe sex, and youth sexuality is
      characterised by multiple sexual partners, not using condoms and transactional
      sex. OBJECTIVES: To minimize the risk of HIV infection, it is necessary to
      understand youth sexuality. In this paper I explore youth sexuality with a
      specific focus on how language influences sexuality. METHODS: I use discourse
      analysis and qualitative research techniques. Purposive sampling, a form of non
      probability sampling was used. I interviewed seventy youth individually or in
      groups and used in-depth semi-structured interviews. RESULTS: The use of language
      influences youth sexuality. Youth have developed a specialised language to talk
      about sex and sexuality and this language has become part of the daily discourse,
      so that unsafe sexual practices become norms and are justified. CONCLUSIONS: The
      realm of language can be a creative way for peer and HIV/AIDS educators to work
      with youth towards creating a healthier sexuality. However, as language always
      occurs in a material context, it is also necessary to work towards changing the
      material environment, such as poverty. This environment not only facilitates the
      development of a particular language but it also encourages unsafe sexual
      practices such as transactional sex.

PMID- 15477189
TI  - Collaboration between the national tuberculosis programme and a non governmental
      organisation in TB/HIV care at a district level: experience from Tanzania.
AB  - BACKGROUND: The increase in tuberculosis and HIV/AIDS patients in many countries
      in Africa including Tanzania, is outstripping the ability of public health
      services to cope. This calls for a closer collaboration between tuberculosis
      programmes and other stakeholders involved in HIV/AIDS care. OBJECTIVE: To
      determine the feasibility of establishing collaboration between the tuberculosis
      programme and an NGO in TB/ HIV care at a district level in Tanzania. METHODS:
      Quantitative and qualitative study designs involving TB as well as HIV suspects
      and patients together with health workers, were conducted between December, 2001
      and September, 2002. RESULTS: A total of 72 patients and 28 key informants were
      involved. The collaboration was in the following areas; voluntary counselling and
      testing for HIV, diagnosis and treatment of TB, referral and follow up of
      patients and suspects, home based care, psychological support and training. Both
      the tuberculosis programme and NGO benefited from the collaboration. TB case
      detection among PLWA increased more than three folds and TB treatment was
      integrated in home based care of NGO. The main barriers identified in this study
      were; poor communication, poor referral system and lack of knowledge and skills
      among health staff. CONCLUSION: The study has shown that it is possible for a
      tuberculosis programme and a non governmental organisation to collaborate in
      TB/HIV care. The study has also identified potential areas of collaboration and
      barriers that needed to be overcome in order to provide such comprehensive
      services at a district level.

PMID- 15477190
TI  - Urinary schistosomiasis in Zimbabwean school children: predictors of morbidity.
AB  - BACKGROUND: The morbid effects of urinary bilharziasis are becoming more evident
      with the advent of sophisticated diagnostics such as ultrasound. However, such
      diagnosis of Schistosoma haematobium morbidity is often hampered by lack of
      funds, proper equipment, or training. OBJECTIVE: We performed a cross-sectional
      investigation of schoolchildren in a highly endemic area of east central Zimbabwe
      in order to assess the utility of a number of simple clinical indicators to
      predict Schistosoma haematobium morbidity. METHODS: Prevalence and intensity of
      S. haematobium infection was determined in 551 schoolchildren, with ultrasound
      examination of the kidneys and bladder performed on 222. The association of a
      number of demographic, parasitological, and clinical parameters with clinical
      outcome was evaluated. RESULTS: Overall, 60% of the children were infected with
      S. haematobium . Although lacking specificity, proteinuria and parasite eggs
      count best predicted bladder pathology. Presence of kidney dilation was
      associated with fatigue and pain upon urination, but these variables were not
      very sensitive. CONCLUSIONS: None of the variables assessed were ideal predictors
      of morbidity. However, the results suggest that a combination of inexpensive,
      simple indicators may allow for improved targeting of S. haematobium treatment to
      those with severe morbidity and better monitoring of the progress of control
      campaigns when more expensive diagnostic methods are not available.

PMID- 15477191
TI  - Health-seeking behavior for malaria among child and adult headed households in
      Rakai district, Uganda.
AB  - BACKGROUND: The number of orphans in Rakai district, Uganda is estimated to be
      34,902 (OCBO, 2000) which translates into 28% of children under the age of 18
      years. Young people who have been orphaned and as a result became heads of
      households must look after themselves and their siblings. These children are
      likely to be faced with several health problems and have to take crucial life
      decisions without parental/adult guidance. OBJECTIVES: This study was conducted
      in order to understand how child-headed households, Rakai district in Uganda
      recognize malaria, their health-seeking behavior when malaria is suspected and
      reasons for the type of behavior compared to the adult-headed households.
      METHODS: A comparative cross-sectional study was conducted in 300 households in
      Rakai district, Uganda, in which 8/23 (35%) of sub-counties and 150 child-headed
      households were included. The closest neighborhood adult-headed household to each
      child-headed household was selected for comparison. Individual interview was
      carried out with the respondents using semi-structure questionnaire. Key
      informant interview and focus group discussions were also conducted. RESULTS: The
      main findings were that the respondents in child-headed households had less
      knowledge on signs and symptoms of simple and severe malaria compared to adult
      heads of households. Respondents in child-headed households were less likely to
      seek health care from health facilities (OR=0.59, CI=0.36-0.97, p-value=0.028).
      There was no significant difference in the time lag before taking first action in
      the two types of households (OR=0.72, CI=0.42-1.22, p-value=0.194). The
      respondents in child-headed households were six times (OR=5.70,CI=2.75-11.91, p
      value<0.001) more likely to use local herb for treatment of malaria than the
      adult heads households. Major reasons stated by the respondents for choosing
      where health care is sought included distance to source of health care, cheap or
      free treatment, availability of drugs, and quick services to patients.
      CONCLUSION: The respondents in child-headed households had less knowledge on
      signs and symptoms of simple and severe malaria and receive too little or late
      health care from health professionals compared to the adult heads of households
      probably due to lack of knowledge and money. Information Communication and
      Education programs should be designed and target the child-headed households and
      supply home packs.

PMID- 15477192
TI  - Alterations in fruit and vegetable beta-carotene and vitamin C content caused by
      open-sun drying, visqueen-covered and polyethylene-covered solar-dryers.
AB  - This study investigated the effects of three drying methods (open sun drying,
      visqueen-covered solar dryer and polyethylene-covered solar dryer) on b-carotene
      and vitamin C content of edible portions of mango fruit (Mangifera indica) and
      cowpea leaves (Vigna unguiculata). Commercial samples were analysed for vitamin C
      by titrimetry and b-carotene by spectrophotometry at 450 nm. Differences in
      vitamin retention and loss associated with the three drying methods were assessed
      by analysis of variance and least significant difference (LSD) at (p<0.05. The
      fresh cowpea leaf b-carotene and vitamin C content was 140.9 and 164.3 mg / 100g
      DM respectively and decreased (p<0.05) with drying. Open sun drying method caused
      the greatest b-carotene and vitamin C loss (58% and 84% respectively), while the
      visqueen-covered solar dryer caused the least loss (34.5% and 71% respectively).
      Blanching cowpea leaves improved b-carotene and vitamin C retention by 15% and
      7.5% respectively. The b-carotene and vitamin C content of fresh ripe mango fruit
      was 5.9 and 164.3 mg/100g DM respectively. Similar to effects on cowpea leaves,
      the mango micronutrient content decreased (p<0.05) with drying. The open sun
      drying method caused the greatest b-carotene (94.2%) and vitamin C (84.5%) loss,
      while the visqueen-covered solar dryer caused the least (73 and 53%
      respectively). These results show that the three solar drying methods cause
      significant loss of pro-vitamin A and vitamin C in dried fruits and vegetables.
      However, open sun drying causes the most loss and the visqueen-covered solar
      dryer the least, making the later a probable better drying technology for fruit
      and vegetable preservation. The drying technologies should be improved to enhance
      vitamin retention.

PMID- 15477193
TI  - Effect of the ferrule on fracture resistance of teeth restored with prefabricated
      posts and composite cores.
AB  - BACKGROUND: The ferrule effect in root treated teeth requiring cast posts and
      cores has been shown to greatly improve fracture resistance. Studies have also
      shown that in the case of a cast post and core, the longer the ferrule, the
      greater the fracture resistance. However few studies have considered the effect
      of different ferrule designs on prefabricated post and composite core systems.
      AIM: This study investigated the effect of different ferrule designs on the
      fracture resistance of teeth incorporating prefabricated posts and composite
      cores. It also assessed the necessity of a post in the restoration of
      endodontically treated teeth. METHODOLOGY: Sixty-two extracted maxillary incisors
      (centrals and laterals) and canines were randomly assigned into three groups and
      restored. Two groups had a prefabricated post and composite core with varying
      ferrule designs. A third group had a core with composite packed into the root
      canal but no post. An Instron universal testing machine was used to apply
      compressive loads until failure occurred. RESULTS: There was no significant
      difference amongst the three groups as regards fracture resistance. The two
      groups with prefabricated posts and composite core required a mean force of 931N,
      std +/-283 and 931N, Std +/-242 to fracture. The third with no post group
      required a mean force of 1036N, std +/-269 to fracture. CONCLUSION: In the
      restoration of an anterior endodontically treated tooth with a prefabricated post
      and composite core and where there is at least 2 mm or more of remaining coronal
      dentine, a ferrule may not be necessary.

PMID- 15477194
TI  - Reiter's syndrome--a case report and review of literature.
AB  - The occurrence of Reiter's Syndrome is rare and not commonly reported in Nigeria.
      This paper reports a case of a 35 yr old male Nigerian with Reiter's Syndrome,
      occurring 1-2 weeks after a bout of a dysenteric illness. The patient presented
      with fever, conjunctivitis, dysentery, urethritis and arthralgia. The joint pains
      involved the left wrist (which was swollen), the right knee and ankle joints. The
      patient was managed conservatively. The case is presented with a view to
      documenting the occurrence of Reiter's Syndrome in an African Nigerian.

PMID- 15477195
TI  - Spontaneous rupture of bladder in puerperium.
AB  - Spontaneous rupture of bladder and extravasation of urine in the peritoneum
      without evidence of trauma is rare. This condition is an emergency. It presents
      in a unique way therefore, the diagnosis and treatment is usually delayed. This
      patient presented with an acute abdominal pain and oliguria. She had delivered
      normally eight days before re-admission. Investigations were done and an
      exploratory laparotomy was performed. There was a tear in the fundus of the
      bladder and the peritoneal cavity contained urine. Peritoneal lavage was done and
      the bladder was repaired in layers. She was put on continuous bladder drainage
      for three weeks followed by bladder training. The bladder resumed its normal
      function. Early diagnosis and appropriate management decreases the morbidity and
      mortality associated with this condition.

PMID- 15477196
TI  - Quality of life and survival of patients with beta-thalassemia major.

PMID- 15477197
TI  - Serum erythropoietin concentration as a diagnostic tool for polycythemia vera.

PMID- 15477198
TI  - Screening selected blood donors with biochemical iron overload for
      hemochromatosis: a regional experience.
AB  - BACKGROUND AND OBJECTIVES: Hemochromatosis is a genetic disorder characterized by
      progressive iron overload which leads to early abnormalities of iron parameters
      (increased transferrin saturation =TS and serum ferritin=SF) and late clinical
      complications. The disease is prevalently due to C282Y and H63D mutations in the
      HFE gene, but additional molecular defects are present in a minority of patients.
      DESIGN AND METHODS: From January to December 2002 we screened first time blood
      donors of Piedmont, a region of North-western Italy, for TS>45%. Individuals with
      TS>45% underwent a second fasting check, SF assessment and molecular tests,
      investigating 12 hemochromatosis-associated molecular defects. RESULTS: A total
      of 13,998 subjects were screened; 868 (6.2%) had TS>45% and were recalled. Four
      hundred and eight-six underwent molecular testing. In this selected population
      allele frequencies of C282Y, H63D and S65C were 6.8%, 22.4% and 1.0%,
      respectively. No rare mutations were detected, except E168Q in HFE. When measured
      during fasting, TS was significantly higher in C282Y homozygotes and H63D/C282Y
      heterozygotes (p<0.05) than in wild type subjects, but not in H63D homozygotes.
      Hyperferritinemia was documented in 32 cases, 9 with wild type genotype. Mean
      age, body mass index (BMI) and alcohol intake were higher in this group than in
      individuals with normal SF. INTERPRETATION AND CONCLUSIONS: This study is an
      example of a large, two-step hemochromatosis screening with moderate effort and
      low cost, that enriches basal C282Y allele frequency by about three-fold.
      Screening based on genotyping only subjects found to have a TS>45% is feasible
      but, in order to be cost effective should be based on the identification of the
      two prevalent mutations even in an area where several forms of hemochromatosis
      have been reported.

PMID- 15477199
TI  - Myosin-like sequences in the malaria parasite Plasmodium falciparum bind human
      erythrocyte membrane protein 4.1.
AB  - BACKGROUND AND OBJECTIVES: Plasmodium falciparum malaria is one of the most
      lethal infectious diseases afflicting humanity. During development within the
      erythrocyte, P. falciparum induces significant modifications to the structure and
      function of the human erythrocyte membrane. This study focused on the
      identification of new protein-protein interactions between host and parasite.
      DESIGN AND METHODS: A novel application of in vitro display technology was used:
      P. falciparum phage display expression libraries were screened against purified
      human erythrocyte protein 4.1. DNA sequencing and bioinformatic analyses were
      used to identify parasite proteins that bind protein 4.1. RESULTS: P. falciparum
      proteins displaying strong binding specificity toward protein 4.1 included five
      hypothetical proteins, erythrocyte binding antigen-175, erythrocyte binding
      ligand-1 like protein and a putative serine/threonine kinase. A common binding
      motif displaying homology to muscle myosin and neurofilament sequences was also
      identified in four of the eight proteins. INTERPRETATION AND CONCLUSIONS: These
      proteins are potentially involved in the invasion and/or release, as well as the
      growth and survival of malaria parasites during development with the red blood
      cell. The characterization of novel protein interactions between P. falciparum
      and erythrocyte membrane protein 4.1 will lead to a better understanding of
      malaria pathogenesis and parasite biology.

PMID- 15477200
TI  - Response to hydroxyurea treatment in Iranian transfusion-dependent beta
      thalassemia patients.
AB  - BACKGROUND AND OBJECTIVES: Hydroxyurea (HU) is known to increase gamma-globin
      chain expression in postnatal life. The efficacy of HU treatment in thalassemia
      patients is still unclear. The aim of this study was to monitor treatment of a
      large cohort of patients with beta-thalassemia major in order to establish the
      response to HU and the associated elements. DESIGN AND METHODS: HU therapy was
      started in 133 patients diagnosed with transfusion-dependent beta-thalassemia in
      1999. The molecular background of the disease, the polymorphisms of the promoter
      region of the genes, the haplotype of the beta-globin gene cluster, the alpha
      gene deletions and the HS2 polymorphism at the locus control region (LCR) of the
      beta-globin gene cluster were studied. RESULTS: We were able to classify three
      categories of response: a good response (61%) in patients who shifted from
      monthly blood transfusion dependency to a stable transfusion-free condition at an
      average Hb level of more than 10 gm/dL; a moderate response (23%) in patients who
      remained transfusion dependent but at longer intervals (6 months or more), and
      non response in patients who, after one year of treatment, remained at the same
      level of transfusion dependency. The correlations with the molecular defects were
      found to be secondary to the presence of the (C-->T) at -158 of the Ggamma gene
      (XmnI polymorphism). The T allele, in linkage to the haplotype I (+----) and to
      the internal beta-globin gene framework 2, was the most significant modulating
      factor involved. INTERPRETATION AND CONCLUSIONS: The good response to HU
      treatment that a significant number of southwest Iranian patients with beta
      thalassemia patients had seems to correlate with particular haplotypes. This
      indicates that HU treatment is a sensible option for transfusion-dependent beta
      thalassemia patients with a favorable molecular background.

PMID- 15477201
TI  - Clinical and histological characterization of liver disease in patients with
      transfusion-dependent beta-thalassemia. A multicenter study of 117 cases.
AB  - BACKGROUND AND OBJECTIVES: Updated information on liver disease in transfusion
      dependent beta-thalassemia is lacking. We conducted a multicenter study within
      the Cooleycare Group to describe the clinical and histopathological features of
      liver disease in currently treated thalassemics. DESIGN AND METHODS: Two-hundred
      and three thalassemics with laboratory signs of liver disease were eligible.
      Liver biopsy was performed in the 129 (63.5%) who consented (age 26+/-7 years).
      Biological samples were sent to the central laboratory. RESULTS: Anti-hepatitis C
      virus (HCV) antibodies were found in 118 patients (91%), 85 (72%) of whom were
      viremic. Ninety-one patients (70%) had abnormal aminotransferase concentrations.
      In the 117 liver biopsies that met the criteria for evaluation (88%), the median
      Ishak's necroinflammatory and fibrosis scores were 4 (range, 0-9) and 2 (range, 0
      6), respectively. Significant fibrosis (score >or=3) was found in 53 (45%); 9
      (8%) had cirrhosis. At multivariate analysis, necroinflammation was related to
      HCV viremia, and fibrosis to increased serum aminotransferases, higher iron
      stores (including serum ferritin, Deugnier's total iron score, and liver iron
      content) and male gender (p<0.05). In HCV-RNA negative subjects, the median total
      iron score was 27 (range, 0-52). Iron accumulated in both mesenchymal cells and
      hepatocytes, and the presence of a lobular gradient was interpreted to indicate
      intestinal hyperabsorption. INTERPRETATION AND CONCLUSIONS: Transfusion-dependent
      thalassemics have mild liver necroinflammation, mainly attributable to HCV
      infection. Significant fibrosis is frequent, and its progression is mostly
      influenced by iron overload which, with current therapy regimens, may be
      attributable to both erythrocyte catabolism and iron hyperabsorption.

PMID- 15477202
TI  - Survival and complications in patients with thalassemia major treated with
      transfusion and deferoxamine.
AB  - BACKGROUND AND OBJECTIVES: Seven Italian centers reported data on survival,
      causes of death and appearance of complications in patients with thalassemia
      major. The interactions between gender, birth cohort, complications, and ferritin
      on survival and complications were analyzed. DESIGN AND METHODS: Survival after
      the first decade was studied for 977 patients born since 1960 whereas survival
      since birth and complication appearance was studied for the 720 patients born
      after 1970. Better survival was demonstrated for patients born in more recent
      years (p<0.00005) and for females (p=0.0003); 68% of the patients are alive at
      the age of 35 years. In the entire population 67% of the deaths were due to heart
      disease. RESULTS: There was a significant association between birth cohort and
      complication-free survival (p<0.0005). The prevalence of complications was: heart
      failure 6.8%, arrhythmia 5.7%, hypogonadism 54.7%, hypothyroidism 10.8%, diabetes
      6.4%, HIV infection 1.7%, and thrombosis 1.1%. Lower ferritin levels were
      associated with a lower probability of heart failure (hazard ratio =3.35,
      p<0.005) and with prolonged survival (hazard ratio = 2.45, p<0.005), using a cut
      off as low as 1,000 ng/mL. INTERPRETATION AND CONCLUSIONS: Survival and
      complication-free survival of patients with thalassemia major continue to
      improve, especially for female patients born shortly before or after the
      availability of iron chelation.

PMID- 15477203
TI  - Diagnostic value of serum erythropoietin level in patients with absolute
      erythrocytosis.
AB  - BACKGROUND AND OBJECTIVES: The diagnosis of polycythemia vera (PV) is based on
      clinical and biological criteria defined by either the Polycythemia Vera Study
      Group (PVSG) or the World Health Organization (WHO). Both the PVSG and WHO PV
      criteria have proved helpful and are extensively used, yet diagnostic strategies
      and scheduling of biological investigations vary. We assessed the value of
      measuring serum erythropoietin (Epo) as a first intention diagnostic test in
      patients with absolute erythrocytosis (AE). DESIGN AND METHODS: Serum and bone
      marrow (BM) samples of 241 patients with a suspicion of erythrocytosis were
      collected in 8 hospital centers. One hundred and ninety had an absolute
      erythrocytosis (116 had PV, 66 had secondary erythrocytosis and 4 had idiopathic
      erythrocytosis). Serum Epo was assayed (ELISA) in 186. Statistical analysis (ROC
      curves) was used to define serum Epo thresholds that were specific for PV and
      secondary erythrocytosis and to analyze the diagnostic value of a low or high
      serum Epo level. RESULTS: A large majority of PV patients (87% or 101/116) had a
      serum Epo level below the normal range in healthy patients (3.3 IU/L), giving
      this value a specificity of 97% with a 97.8% positive predictive value for the
      diagnosis of PV. Statistical analysis (ROC curves) defined two thresholds
      allowing a specific and direct diagnosis of 65.6% (65/99) of untreated PV (Epo <
      1.4 IU/L) and 19.7% (13/66) of those with secondary erythrocytosis (Epo > 13.7
      IU/L). INTERPRETATION AND CONCLUSIONS: Based on these data, we propose that
      measurement of serum Epo level, a simple, reliable and inexpensive test, should
      be considered as a first intention diagnostic test for patients with absolute
      erythrocytosis.

PMID- 15477204
TI  - Early down-regulation of Bcl-xL expression during megakaryocytic differentiation
      of thrombopoietin-induced CD34+ bone marrow cells in essential thrombocythemia.
AB  - BACKGROUND AND OBJECTIVES: Essential thrombocythemia (ET) is a chronic
      myeloproliferative disorder with abnormal megakaryocyte/platelet production.
      Recent studies have found that Bcl-xL, as a member of the bcl-2 family of
      proteins that inhibit apoptosis, is essential in megakaryocytic differentiation.
      In this study the expression of Bcl-xL was evaluated during megakaryocytic
      differentiation in ET patients. DESIGN AND METHODS: To study the role of Bcl-xL
      in megakaryocyte differentiation, we evaluated the effect of small interfering
      RNA (siRNA) on the expression of Bcl-xL. CD34+ cells from patients with ET,
      chronic myeloid leukemia (CML), polycythemia vera (PV) and normal individuals
      were cultured in serum-free medium supplemented with thrombopoietin (TPO).
      Immunocytochemical staining and flow cytometric analysis were used to evaluate
      the Bcl-xL expression during megakaryocytic differentiation of CD34+ cells.
      RESULTS: When exposured to si-Bcl-xL, the percentage of K562 cells induced into
      megakaryocytes in 72 hours was lower than the corresponding percentage of control
      cells. CD41a+ cells from the three groups of patients and the control group were
      cultured. At day 10, the percentage of Bcl-xL- cells in CD41a+ cells from ET
      patients was 61.0+/-28.1%, which was significantly higher than that from patients
      with CML (2.5+/-20.9%), PV (33.6+/-10.0%) or control subjects (15.1+/-13.0%).]
      INTERPRETATION AND CONCLUSIONS: These results demonstrate that Bcl-xL is down
      regulated early during in vitro differentiation of megakaryocytes from ET
      patients; this might reflect an early entry of megakaryocytes into a degenerating
      mature stage.

PMID- 15477205
TI  - A standardized endogenous megakaryocytic erythroid colony assay for the diagnosis
      of essential thrombocythemia.
AB  - BACKGROUND AND OBJECTIVES: The reliability of assays of endogenous megakaryocytic
      colony (EMC) and endogenous erythroid colony (EEC) formation for the diagnosis of
      thrombocytoses remains controversial. We tested the suitability of a recently
      developed collagen-based assay of EMC formation for the diagnosis of essential
      thrombocythemia (ET). DESIGN AND METHODS: This was a multicenter (8 laboratories)
      study including 121 patients: 82 with ET and 39 with reactive thrombocytoses
      (RT). EMC and EEC were assessed in each laboratory in serum-free, cytokine-free,
      standardized collagen gel assays; bone marrow (BM) and peripheral blood (PB) were
      tested in parallel. RESULTS: In PB cultures, only EEC were specific for ET. In BM
      cultures, both EMC and EEC were specific for ET and present in assays of 77.8%
      (EMC) and 33.3% (EEC) of ET patients. Altogether, 80.2% of ET patients had BM EMC
      and/or EEC, whereas none of the patients with RT did. INTERPRETATION AND
      CONCLUSIONS: When performed with BM progenitors for the diagnosis of
      thrombocytoses, positivity of the standardized EMC/EEC assay in collagen is
      specific (100%) and detects 80% of ET.

PMID- 15477206
TI  - The value of fluorescence in situ hybridization for the detection of 11q in
      multiple myeloma.
AB  - BACKGROUND AND OBJECTIVES: A large number of chromosomal abnormalities have been
      detected in multiple myeloma (MM). The most frequent are chromosome 13q deletions
      and translocations affecting the immunoglobulin heavy chain gene (IGH). Recent
      studies using comparative genomic hybridization (CGH) have shown that gains of
      11q represent one of the most frequent genomic changes in MM. However CGH is not
      generally used in routine clinical laboratories. DESIGN AND METHODS: In the
      present study, efficiency of fluorescent in situ analysis (FIS)H analysis in the
      detection of 11q abnormalities in MM patients was investigated. Cytogenetic and
      FISH studies with three different specific probes for the regions containing the
      genes BCL1 (11q13), ATM (11q22) and MLL (11q23) were simultaneously performed in
      52 patients: 9 cases with 11q abnormalities detected by conventional cytogenetics
      and 43 cases without 11q abnormalities. FISH analysis identified 11q aberrations
      that were undetected by cytogenetics in 16 out the 43 cases (37%). RESULTS: Gains
      on 11q were present in 13 cases (30%) while rearrangements on 11q were observed
      in the remaining 3 cases. No losses were found. All 11q gains involved the three
      regions analyzed (BCL1, ATM and MLL genes) while only rearrangements of BCL1 were
      observed. In all control cases the 11q alterations were confirmed by FISH. A good
      overall correlation between CGH and FISH was observed. Nevertheless gains on
      BCL1, ATM and MLL genes were observed in 3 cases displaying a normal CGH.
      INTERPRETATION AND CONCLUSIONS: In summary, chromosomal abnormalities on 11q are
      frequent in MM. FISH studies demonstrate a high sensitivity at detecting this
      abnormality and should be used in the routine evaluation of MM.

PMID- 15477207
TI  - Application of a diagnostic algorithm for inherited thrombocytopenias to 46
      consecutive patients.
AB  - BACKGROUND AND OBJECTIVES: The Italian Gruppo di Studio delle Piastrine recently
      developed a diagnostic algorithm to assist clinicians in the diagnosis of
      inherited thrombocytopenias. This algorithm is based on the simplest possible
      diagnostic investigations and can also be used in centers that are not highly
      specialized. The aim of the present study was to validate this diagnostic
      algorithm by applying it to a case series of genetic thrombocytopenias. DESIGN
      AND METHODS: The diagnostic algorithm was applied retrospectively to 46
      consecutive patients observed during the last five years at a single institution.
      Twenty-eight were affected by defined illnesses or their variants, while 18 had a
      disorder that did not fit the criteria for any known genetic thrombocytopenia.
      The study was based on the evaluation of clinical records and laboratory tests.
      RESULTS: The diagnostic algorithm recognized: 4 homozygous and 4 heterozygous
      Bernard-Soulier syndromes, 11 MYH9-related diseases, one von WillebrandOs disease
      type 2B, one gray platelet syndrome and one X-linked thrombocytopenia with
      thalassemia. Moreover, it identified 4 patients with the clinical and laboratory
      features of heterozygous Bernard-Soulier syndrome not caused by mutations in the
      coding region of the GPIbalpha, GPIbbeta, GPIX or GPV genes, and two patients
      with the clinical phenotype of MYH9-related disease but without MYH9 mutations.
      Since the diagnostic flow chart did not allow prompt recognition of two subjects
      with MYH9-related disease, we introduced a small change to the previously
      proposed flow chart to obviate this defect. INTERPRETATION AND CONCLUSIONS: The
      diagnostic algorithm correctly diagnosed 26 of 28 patients with known disorders
      or phenotypic variants of known disorders. By a simple modification of the
      investigation sequence, its sensitivity reached 100%. The algorithm also
      identified 18 patients with new, as yet uncharacterized forms of genetic
      thrombocytopenia.

PMID- 15477208
TI  - Validation of plasma fibrinogen as a marker of carotid atherosclerosis in
      subjects free of clinical cardiovascular disease.
AB  - BACKGROUND AND OBJECTIVES: Fibrinogen has been found to be an independent risk
      factor for cardiovascular disease. The aim of this study was to validate the
      measurement of plasma fibrinogen as a marker of subclinical atherosclerosis in a
      series of asymptomatic subjects (n=519, median age 55.5 years, 80% men). DESIGN
      AND METHODS: All individuals had a complete clinical examination, lipid profile
      (cholesterol and its high and low density lipoprotein fractions and
      triglycerides), global vascular risk assessment (PROCAM), and B-mode
      ultrasonography of the carotid arteries to determine the intima-media thickness
      (IMT) and the presence of atheroma plaques. C-reactive protein (CRP), and von
      Willebrand factor (vWF) were also measured in all subjects as markers of
      inflammation/endothelial damage. RESULTS: In the univariate model, a positive
      relationship was found between plasma fibrinogen concentration and carotid IMT
      (p<0.001). Fibrinogen concentration also correlated positively with age
      (p<0.001), systolic blood pressure (p<0.001), smoking (p<0.05), diabetes
      (p<0.05), PROCAM (p<0.001), CRP and vWF (p<0.001). In the multivariate analysis,
      the association of fibrinogen with carotid IMT remained significant (p=0.008)
      after adjustment for all parameters analyzed. INTERPRETATION AND CONCLUSIONS: In
      a population sample of adults without clinically overt atherosclerotic disease,
      elevated fibrinogen levels was related to carotid IMT independently of a wide
      range of important confounding variables. Plasma fibrinogen may represent a
      systemic marker of carotid atherosclerosis.

PMID- 15477209
TI  - Quality control of bacterial contamination in autologous peripheral blood stem
      cells for transplantation.
AB  - BACKGROUND AND OBJECTIVES: Microbiological follow-up is part of quality control
      of peripheral blood stem cell (PBSC) manipulation. DESIGN AND METHODS: We
      prospectively studied microbiological cultures performed in 865 consecutive
      untreated autologous PBSC harvests from 348 patients. Our aim was to know the
      rate of microbiological contamination, the optimum moment to evaluate the sample
      and the clinical significance of the positive findings. RESULTS: Fifty-nine of
      the 852 samples (6.9%) yielded a positive culture after PBSC collection (sample
      1) and 62 samples also yielded positive results before cryopreservation (7.2%)
      (sample 2). At the time of the analysis, a total of 520 aphereses had been
      infused and the number of positive cultures after thawing (sample 3) and after
      washing (sample 4; 82 aphereses) was 5.4% and 2.3%, respectively. Most of the
      positive cultures were due to coagulase-negative staphylococci (48 isolates).
      After thawing 15 coagulase-negative staphylococci and 2 enterococci isolates were
      recovered. Comparison between samples using a marginal homogeneity test showed no
      differences in the rate of contamination observed at the different sampling
      points. INTERPRETATION AND CONCLUSIONS: Positive microbiological findings in
      collected PBSC are not due to contamination within the laboratory.
      Cryopreservation using DMSO does not eradicate bacteria and manipulation does not
      seem to affect results. To simplify the procedure it would be possible to
      eliminate the microbiological controls performed immediately before
      cryopreservation.

PMID- 15477210
TI  - Reducing transplant-related mortality after allogeneic hematopoietic stem cell
      transplantation.
AB  - BACKGROUND AND OBJECTIVES: Transplant-related mortality (TRM) following
      allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to be
      related to disease stage, duratiion of disease and type of donor. Furthermore,
      the outcome of transplants performed in the 1990s appears to be better than that
      of transplants done in the previous decade. The aims of this study were to
      determine whether these relationships still hold and whether the outcome of
      transplants is continuing to improve. DESIGN AND METHODS: We analyzed 1180
      consecutive patients with leukemia (n=979) or other hematologic malignancies
      (n=201) undergoing HSCT in 4 time periods: before 1990, 1991-1995, 1996-2000, and
      2001-2002. Changes during these eras include increasing patient age, more
      unrelated transplants, more patients with advanced disease, different graft
      versus-host disease (GvHD) prophylaxis, and different management of infections.
      RESULTS: The actuarial 2-year transplant-related mortality (TRM) differed
      significantly between the transplant eras (p<0.001) with a significant
      interaction with disease phase (p=0.018). In patients in first remission (n=585)
      TRM was 34%, 25%, 21% and 6% in the four transplant eras. The reduction in TRM
      was less evident in patients in second remission (n=284) (37%, 35%, 30%, 25%) and
      absent in relapsed patients (n=311) (TRM=45%, 41%, 29%, 51%). This is a
      consequence of reductions in GvHD, infections and multiorgan failure among
      patients in remission but not among those who relapse. The actuarial 2-year
      survival has improved significantly in patients in first remission (54%, 66%,
      72%, 78%) but not in those in second remission (38%, 46%, 52%,45%), or relapsed
      patients (31%, 25%, 36%, 21%). INTERPRETATION AND CONCLUSIONS: In conclusion, TRM
      has been significantly reduced in first remission patients, suggesting an
      allograft should be considered in this phase, when appropriate, without delay.
      There has been no improvement in survival for patients beyond first remission,
      due to persisting high risk of infections and organ toxicity, a possible
      consequence of prolonged pre-transplant chemotherapy and neutropenia.

PMID- 15477211
TI  - Cytomegalovirus reactivation during alemtuzumab therapy for chronic lymphocytic
      leukemia: incidence and treatment with oral ganciclovir.
AB  - BACKGROUND AND OBJECTIVES: Although alemtuzumab (campath-1H) has been
      successfully used in patients with untreated or previously treated chronic
      lymphocytic leukemia (CLL), a variable incidence of cytomegalovirus (CMV)
      reactivation has been described. No prospective reports currently provide results
      of the use of oral ganciclovir as pre-emptive therapy in patients with CMV
      reactivation during alemtuzumab treatment. DESIGN AND METHODS: We designed a
      prospective study in 12 patients with pretreated CLL with the aim of evaluating
      the incidence of CMV reactivation during alemtuzumab treatment and the role of
      oral ganciclovir as pre-emptive therapy and in preventing CMV organ disease.
      RESULTS: In the 12 CLL patients being treated with alemtuzumab, 8 patients (66%)
      had CMV reactivation, as detected by antigenemia and/or CMV DNA. No patient
      showed clinical evidence of CMV disease. The alemtuzumab was discontinued and the
      patients were immediately treated with oral ganciclovir 1000 mg tid. After a
      median of 14 days of antiviral therapy all patients achieved negative CMV
      polymerase chain reaction (PCR) assays and/or antigenemia. No patients showed
      further CMV reactivation up to the end of the study. INTERPRETATION AND
      CONCLUSIONS: CMV reactivaction, studied with periodic analysis of antigenemia and
      PCR, is frequent in previously treated CLL patients receiving alemtuzumab therapy
      although only sporadic cases of CMV disease have been reported. Using oral
      ganciclovir, the response to therapy was prompt, there was no progression to CMV
      disease, and no relevant clinical toxicity, thus sparing unnecessary
      hospitalization. Oral ganciclovir may be used as pre-emptive therapy in all
      patients who develop CMV reactivation during alemtuzumab treatment.

PMID- 15477212
TI  - Innovative cell-based therapies in onco-hematology: what are the clinical facts ?
AB  - BACKGROUND AND OBJECTIVES: One of the few measurable clinical results obtained by
      the use of somatic cells in onco hematology is the clear-cut effect donor
      leukocyte infusions (DLI) in patients with chronic myeloid leukemia (CML) who
      relapse after an allogeneic bone marrow transplantation (BMT). From then on much
      research has focused on the use of cells to treat different aspects of oncologic
      diseases from leukemia relapse to development in BMT recipients. METHODS AND
      INFORMATION SOURCES: In this review we critically and schematically summarize the
      cell-based therapies which have led to a clinical application and recapitulate
      the results. RESULTS AND STATE OF THE ART: Although the overall numbers of
      successfully treated patients is small, therapy has been shown to be safe and
      effective in a variety of clinical contexts in oncohematology. PERSPECTIVES:
      Preliminary data will have to be validated in well designed clinical trials with
      cells generated by reproducible methods and in accreditated structures working
      according to Good Manufacturing Practices (GMP).

PMID- 15477213
TI  - Onset of X-linked sideroblastic anemia in the fourth decade.
AB  - We report the case of a 40-year female who manifested late onset, pyridoxine
      refractory X-linked sideroblastic anemia, heterozygous for the first described
      frameshift ALAS2 mutation, CD506-507 (-C). On presentation she had macrocytic
      anemia with severe iron overload.

PMID- 15477214
TI  - Lack of response to imatinib mesylate in a patient with accelerated phase
      myeloproliferative disorder with rearrangement of the platelet-derived growth
      factor receptor beta-gene.
AB  - Imatinib mesylate has been reported to produce positive results in atypical
      chronic myeloproliferative disorders (CMD) with chromosomal translocations that
      disrupt the platelet-derived growth factor receptor beta gene (PDGFRB). We used
      imatinib to treat a 49-year old man with atypical CMD in accelerated phase and
      the H4 (D10S170)-PDGFRB fusion gene. After 3 months of treatment, we observed
      grade 4 hematologic toxicity and a lack of response.

PMID- 15477215
TI  - The effects of hydroxyurea on PRV-1 expression in patients with essential
      thrombocythemia and polycythemia vera.
AB  - The study was designed to investigate the influence of hydroxyurea (HU) treatment
      on PRV-1 expression. Eighteen newly diagnosed patients with essential
      thrombocythemia (ET) or polycythemia vera (PV) were included. HU significantly
      increased PRV-1 gene expression in the early stage of treatment.

PMID- 15477216
TI  - Molecular remission with arsenic trioxide in patients with newly diagnosed acute
      promyelocytic leukemia.
AB  - Thirty six APML patients achieving hematological remission with As2O3 were
      serially monitored using RT-PCR. Though only 5.5% achieved molecular remission at
      induction remission, 94.5% became negative during consolidation. At 20 months
      follow-up, 85% remain in remission but longer follow up studies are needed to
      monitor late relapses.

PMID- 15477217
TI  - Quantification of DEK-CAN fusion transcript by real-time reverse transcription
      polymerase reaction in patients with t(6;9) acute myeloid leukemia.
AB  - Real-time reverse transcription polymerase reaction (RT-PCR) was used to examine
      DEK-CAN transcript levels in serial samples from three patients with t(6;9) acute
      myeloid leukemia treated with intensive chemotherapy. All three patients achieved
      short first clinical remission, but without achieving RT-PCR negativity. DEK-CAN
      level significantly increased in two patients before relapse, while in the third
      a level of 2x10(-3) in remission bone marrow preceded relapse by 2 months.

PMID- 15477218
TI  - The achievement of molecular complete remission during treatment with imatinib
      mesylate correlates with relapse-free survival in bcr/abl-positive acute lymphoid
      leukemia patients.
AB  - Using quantitative reverse-transcription polymerase chain reaction we
      investigated the significance of achieving molecular complete remission (CR) in
      12 patients with bcr/abl-positive acute lymphocytic leukemia treated with
      imatinib. The 6 patients who achieved molecular CR had significantly better
      relapse-free survival (RFS) than the others (9 vs 4 months) (p=0.000). Moreover,
      the 6 patients with a bcr-abl/GAPDHx100,000 ratio <2 after 4 weeks of treatment
      had significantly better RFS (10.5 vs 4 months) (p=0.004).

PMID- 15477219
TI  - Molecular detection of minimal residual disease is associated with early relapse
      in adult acute lymphoblastic leukemia.
AB  - Several studies in childhood acute lymphoblastic leukemia (ALL) have documented
      that molecular detection of minimal residual disease (MRD) based on screening for
      T-cell receptor and immunoglobulin gene rearrangements can identify patients at a
      high risk of relapse. In our experience, evaluation of MRD in adult ALL can help
      to identify high risk patients.

PMID- 15477220
TI  - Combined semi-nested polymerase chain reaction and heteroduplex analysis for
      detecting monoclonality of IgH rearrangement in patients with follicular
      lymphoma.
AB  - A new, sensitive method combining seminested polymerase chain reaction (PCR) and
      heteroduplex analysis was used to detect follicular lymphoma (FL) cells in
      peripheral blood. Based on the detection of IgH rearrangement in DNA from
      peripheral blood leukocytes, the method demonstrated the presence of monoclonal B
      cells in FL patients with high frequency.

PMID- 15477221
TI  - Sequential chemotherapy regimens followed by high-dose therapy with stem cell
      transplantation in mantle cell lymphoma: an update of a prospective study.
AB  - This study is a long-term follow-up analysis evaluating clinical outcome of
      patients with mantle-cell lymphoma treated by the sequential CHOP and DHAP
      chemotherapy followed by autografting. The median overall survival of 81 months
      (95% CI, 66-not reached) and the median event free survival of 51 months (95% CI,
      43-not reached) confirm the improvement in outcome obtained by such protocol.

PMID- 15477222
TI  - Mitogen-activated protein kinase signalling pathways in IL-1 beta-dependent rat
      airway smooth muscle proliferation.
AB  - Asthma is associated with abnormal airway smooth muscle (ASM) growth that may
      contribute to airway narrowing and hyperresponsiveness. We investigated the role
      of mitogen-activated protein kinase (MAPK) pathway in IL-1beta induced ASM
      proliferation in the rat. Rat tracheal ASM cells were dissociated and maintained
      in culture. We examined the effect of selective MAPK inhibitors, SB239063 (a p38
      MAPK inhibitor), U0126 (a mitogen-activated and extracellular regulated kinase
      kinase, MEK-1, inhibitor which inhibits downstream extracellular regulated
      kinase, ERK, activity), and SP600125 (a c-jun N-terminal kinase, JNK, inhibitor)
      on IL-1beta-induced proliferation. Proliferation of ASM cells was significantly
      increased following exposure to IL-1beta in a dose-dependent manner. p38, JNK and
      ERK MAPKs were activated by IL-1beta in a time-dependent manner, with peak
      activation time at 30, 60 min and at 6 h, respectively. This activation was
      inhibited by their respective inhibitors. SP600125 (20 microM) had no effect on
      IL-1beta-induced ERK and p38 phosphorylation. SB239063, U0126 and SP600125 dose
      dependently inhibited IL-1beta-dependent proliferation at doses that inhibit the
      activities of p38, ERK and JNK MAPKs, respectively. No additive or synergistic
      effects were observed on proliferative responses with any combination of these
      compounds. In conclusion, the three major MAPK pathways, ERK as well as the p38
      MAPK and JNK pathways, are independent regulators of IL-1beta-dependent
      proliferation of rat ASM.

PMID- 15477223
TI  - Noncompetitive antagonism of BIBN4096BS on CGRP-induced responses in human
      subcutaneous arteries.
AB  - We investigated the antagonistic effect of 1-piperidinecarboxamide, N-[2-[[5amino
      l-[[4-(4-pyridinyl)-l-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4
      hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)
      (BIBN4096BS) on the calcitonin gene-related peptide (CGRP)-induced responses by
      using isometric myograph and FURA-2 technique in human subcutaneous arteries
      removed in association with abdominal surgery. BIBN4096BS, at the concentration
      of 1 pm, had no significant effect on the CGRP-induced relaxation in these
      vessels. At the concentration of 10 pM, BIBN4096BS had a competitive antagonistic
      like behaviour characterized by parallel rightward shift in the log CGRP
      concentration-tension curve with no depression of the E(max). At the higher
      concentrations (0.1 and 1 nM), BIBN4096BS had a concentration-dependent
      noncompetitive antagonistic effect on the CGRP-induced responses. The efficacy
      and potency of CGRP was significantly greater in the smaller (lumen diameter
      approximately 200 microM) human subcutaneous arteries compared to the larger
      ones. The apparent agonist equilibrium dissociation constant, K(A), for CGRP(1)
      receptors in the human subcutaneous arteries was approximately 1 nM. Analysis of
      the relationship between receptor occupancy and response to CGRP indicates that
      the receptor reserve is relatively small. Using reverse transcriptase-polymerase
      chain reaction (RT-PCR), the presence of mRNA sequences encoding the calcitonin
      receptor-like receptor, receptor activity modifying protein (RAMP1, RAMP2, RAMP3)
      and receptor component protein were demonstrated in human subcutaneous arteries,
      indicating the presence of CGRP(1)-like receptor and the necessary component for
      the receptor activation. In conclusion, the inhibitory action of BIBN4096BS at
      the low concentration (10 pM) on the CGRP-tension curve (but not intracellular
      calcium concentration ([Ca(2+)](i)) resembles what is seen with a reversible
      competitive antagonist. However, at the higher concentrations (0.1 and 1 nM),
      BIBN4096BS acts as a selective noncompetitive inhibitor at CGRP(1) receptors in
      human subcutaneous arteries.

PMID- 15477225
TI  - Contribution of the endothelin and renin-angiotensin systems to the vascular
      changes in rats chronically treated with ouabain.
AB  - Renin-angiotensin and endothelin systems are involved in the cardiovascular
      effects produced by treatment with ouabain. We recently demonstrated that the
      contractile response to phenylephrine is decreased in ouabain-treated rats. The
      present study investigated whether endothelin-1 (ET-1) and angiotensin II (Ang
      II) contributes to the vascular changes observed in rats chronically treated with
      ouabain. Wistar rats were treated with ouabain (8.0 microg day(-1), s.c. pellets
      for 5 weeks) alone or in combination with an endothelin type A receptor (ET(A))
      antagonist, BMS182874 (40 mg kg(-1) day(-1), per gavage) or an angiotensin type 1
      (AT(1)) receptor antagonist, losartan (15 mg kg(-1) day(-1), p.o.). Treatment
      with ouabain increased systolic blood pressure and treatment with either losartan
      or BMS182874 prevented the development of ouabain-induced hypertension. The
      sensitivity and maximal response for phenylephrine were reduced in aortic rings
      from ouabain-treated rats. Removal of the endothelium or in vitro exposure to an
      inhibitor of nitric oxide synthase (NOS), N-nitro-L-arginine methyl ester (L
      NAME, 100 microM) increased the responses to phenylephrine, an effect that was
      more pronounced in aortas from ouabain-treated rats. Endothelial NOS protein
      (eNOS) expression was increased after ouabain treatment. Treatment with
      BMS182874, but not with losartan, prevented the effects of ouabain on the
      reactivity of phenylephrine and in eNOS protein expression. Gene expression of
      pre-pro-ET-1 and ET(A) receptors was increased in aortic rings from ouabain
      treated rats. ET(B) receptor gene expression was not altered by ouabain
      treatment. In conclusion, our results suggest that endothelin and angiotensin
      systems play an important role in the development of ouabain-induced
      hypertension. However, ET-1, by activation of ET(A) receptors, but not Ang II,
      contributes to changes in vascular reactivity to phenylephrine induced by chronic
      treatment with ouabain.

PMID- 15477226
TI  - Beta 2-adrenergic receptor regulation of human neutrophil function is sexually
      dimorphic.
AB  - While the mechanisms underlying the marked sexual dimorphism in inflammatory
      diseases are not well understood, the sexually dimorphic sympathoadrenal axis
      profoundly affects the inflammatory response. We tested whether adrenergic
      receptor-mediated activation of human neutrophil function is sexually dimorphic,
      since neutrophils provide the first line of defense in the inflammatory response.
      There was a marked sexual dimorphism in beta(2)-adrenergic receptor binding,
      using the specific beta(2)-adrenergic receptor ligand, [(3)H]-dihydroalprenolol,
      with almost three times more binding sites on neutrophils from females (20,878 +/
      2470) compared to males (7331 +/- 3179). There was also a marked sexual
      dimorphism in the effects of isoprenaline, a beta-adrenergic receptor agonist,
      which increased nondirected locomotion (chemokinesis) in neutrophils obtained
      from females, while having no effect on neutrophils from males. Isoprenaline
      stimulated the release of a chemotactic factor from neutrophils obtained from
      females, but not from males. This chemotactic factor acts on the G protein
      coupled CXC chemokine receptor 2 (CXCR2) chemokine receptor, since an anti-CXCR2
      antibody and the selective nonpeptide CXCR2 antagonist SB225002, inhibited
      chemotaxis produced by this factor. While interleukin- (IL-) 8 is a principal
      CXCR2 ligand, isoprenaline did not produce an increase in IL-8 release from
      neutrophils. IL-8-induced chemotaxis was inhibited in a sexually dimorphic manner
      by isoprenaline, which also stimulated release of a mediator from neutrophils
      that induced chemotaxis, that was inhibited by anti-CXCR2 antibodies. These
      findings indicate an important role for adrenergic receptors in the modulation of
      neutrophil trafficking, which could contribute to sex-differences in the
      inflammatory response.

PMID- 15477227
TI  - IL-18 together with anti-CD3 antibody induces human Th1 cells to produce Th1- and
      Th2-cytokines and IL-8.
AB  - Although IL-18 was initially regarded as a factor that enhances IFN-gamma
      production from Th1 cells, later studies revealed its potential to induce Th2
      cytokine production from T cells, NK cells and basophils/mast cells. Very
      recently, we demonstrated that passively transferred memory phenotype Th1 cells
      induce airway inflammation and hyperresponsiveness in a host mouse by production
      of Th1-, Th2-cytokines, GM-CSF and chemokines, when the transferred cells are
      stimulated in the host mice with nasally administered Ag and IL-18. Moreover, IL
      18 is suggested to contribute to asthma exacerbation in human patients.
      Therefore, it is important to determine whether human Th1 cells also have the
      potential to produce these soluble factors when stimulated with anti-CD3 and IL
      18 in vitro. Here we demonstrated that only Th1 cells, but not Th2 cells, produce
      IFN-gamma, IL-13, GM-CSF and IL-8 after stimulation with anti-CD3 and IL-18.
      Furthermore, highly purified IFN-gamma-producing Th1 cells have the same
      potential. Thus, human Th1 cells may become very harmful cells, when stimulated
      with Ag and IL-18 in vivo, and produce IFN-gamma, IL-13, GM-CSF and IL-8, which
      in combination might induce severe inflammation such as airway inflammation.

PMID- 15477228
TI  - Role of c-Jun N-terminal kinase on lipopolysaccharide induced maturation of human
      monocyte-derived dendritic cells.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that play a pivotal
      role in the initiation of T cell-dependent immune responses. Immature DCs
      obtained from peripheral blood CD14+ monocytes by culture with granulocyte
      macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4)
      differentiate into mature DCs upon stimulation with lipopolysaccharide (LPS). At
      least three families of mitogen-activated protein kinases (MAPKs), that is,
      extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK) and
      p38 MAPK, are involved in the DC maturation process. We report investigations of
      the role of JNK in the maturation of human monocyte-derived DCs. SP600125, a
      specific inhibitor of JNK, inhibited the LPS-induced up-regulation of CD80, CD83,
      CD86 and CD54, but augmented the up-regulation of HLA-DR. SP600125 slightly
      inhibited the down-regulation of FITC-dextran uptake during DC maturation.
      However, SP600125 did not affect the LPS induced up-regulation of allostimulatory
      capacity of DCs. SP600125 inhibited the release of IL-12 p70 and TNF-alpha from
      mature DCs. Although autologous T cells primed by the ovalbumin (OVA)-pulsed
      mature DCs produced IFN-gamma, but not IL-4, OVA-pulsed SP600125-treated mature
      DCs could initiate IL-4 production from autologous T cells. In contrast, a p38
      MAPK inhibitor, SB203580, profoundly inhibited the phenotypic and functional
      maturation of DCs, while an ERK inhibitor, PD98059, had little or no effect.
      Taken together, the JNK signaling pathway appears to have a role that is distinct
      from the p38 MAPK and ERK cascades in the maturation process of DCs, and may be
      involved in the augmentation of Th2-prone T cell responses when it is suppressed.

PMID- 15477229
TI  - The role of antigenic peptide in CD4+ T helper phenotype development in a T cell
      receptor transgenic model.
AB  - CD4+ Th1 cells play a critical role in the induction of cell-mediated immune
      responses that are important for the eradication of intracellular pathogens.
      Peptide-25 is the major Th1 epitope for Ag85B of Mycobacterium tuberculosis and
      is immunogenic in I-Ab mice. To elucidate the role of the TCR and IFN-gamma/IL-12
      signals in Th1 induction, we generated TCR transgenic mice (P25 TCR-Tg)
      expressing TCR alpha- and beta-chains of Peptide-25-reactive cloned T cells and
      analyzed Th1 development of CD4+ T cells from P25 TCR-Tg. Naive CD4+ T cells from
      P25 TCR-Tg differentiate into both Th1 and Th2 cells upon stimulation with anti
      CD3. Naive CD4+ T cells from P25 TCR-Tg preferentially develop Th1 cells upon
      Peptide-25 stimulation in the presence of I-Ab splenic antigen-presenting cells
      under neutral conditions. In contrast, a mutant of Peptide-25 can induce solely
      Th2 differentiation. Peptide-25-induced Th1 differentiation is observed even in
      the presence of anti-IFN-gamma and anti-IL-12. Furthermore, naive CD4+ T cells
      from STAT1 deficient P25 TCR-Tg also differentiate into Th1 cells upon Peptide-25
      stimulation. Moreover, Peptide-25-loaded I-Ab-transfected Chinese hamster ovary
      cells induce Th1 differentiation of naive CD4+ T cells from P25 TCR-Tg in the
      absence of IFN-gamma or IL-12. These results imply that interaction between
      Peptide-25/I-Ab and TCR may primarily influence determination of the fate of
      naive CD4+ T cells in their differentiation towards the Th1 subset.

PMID- 15477230
TI  - Antigen localization within the splenic marginal zone restores humoral immune
      response and IgG class switch in complement C4-deficient mice.
AB  - Defects of early complement components (C1, C4 and C2) are associated with the
      development of systemic lupus erythematosus (SLE). The availability of complement
      knockout mice has increased our knowledge on the role of complement in the
      regulation of adaptive immunity. An impaired removal of apoptotic bodies, a
      disturbed clearance of IgG immune complexes (ICs) and an insufficient B-cell
      regulation via complement receptors CD21/CD35 have been discussed as explanations
      for the induction of autoimmunity; however, a unifying hypothesis for the loss of
      B-cell tolerance in the absence of C1 or C4 is still lacking. Using IgM
      containing ICs, we observed a significant accumulation of antigen within the
      splenic marginal zone (MZ) of C4-deficient mice but not in C3-deficient or
      complement receptors CD21/CD35-deficient mice. The targeting of antigen toward
      the MZ restored adaptive immunity (antibody response and class switch) in C4
      deficient animals. A new explanation for the association of SLE and complement C4
      deficiency would be that in the absence of C4, natural antibodies (IgM type)
      localize more self-antigen toward the MZ so that the auto-antibody response is
      increased and autoimmune disease ensues. As such, an inadequate localization of
      self-antigens might be responsible for the annulment of peripheral B-cell
      tolerance in the absence of C4.

PMID- 15477231
TI  - Statistical recognition of random and regular phyllotactic patterns.
AB  - AIMS: A statistical method used in ecology is adapted to characterize the degree
      of order in phyllotactic systems. SCOPE: The test consists of subdividing a
      planar projection of the stem apical meristem into 16 sectors and counting the
      number of primordia appearing in each. By dividing the sum of squared deviations
      by the mean number of primordia per sector the chi-square (chi2) is obtained.
      When there are a total number of 20 primordia, if the chi2 is less than 6.26, the
      phyllotaxis is spiral; if it is between 6.26 and 27.5 the phyllotaxis is random;
      and if it is greater than 27.5, the phyllotaxis is distichous or whorled (level
      of significance alpha = 5 %). It is also possible to remove one or more sectors.
      If there are k sectors, the two critical values delimiting the random zone will
      be found in a chi2 table for k - 1 degrees of freedom. CONCLUSIONS: The method is
      applied to the analysis of sho mutants described by Itoh et al. in 2000 (Plant
      Cell 12: 2161-2174). The results obtained are in agreement with the theoretical
      analysis showing that a whorled or spiral phyllotactic system may contain a
      certain number of randomly distributed elements without losing its regular global
      structure.

PMID- 15477232
TI  - Low levels of allozyme variability in the threatened species Antirrhinum
      subbaeticum and A. pertegasii (Scrophulariaceae): implications for conservation
      of the species.
AB  - AIMS: This study was designed to compare levels of genetic variation and its
      partitioning in three related species of Antirrhinum, A. subbaeticum, A.
      pertegasii and A. pulverulentum, and to check the hypothesis that species with
      small total population size have lower levels of genetic variability than those
      with bigger ones. This information should contribute to the development of
      conservation strategies of rare endemic species of Antirrhinum. METHODS: One
      hundred and seventy-seven plants were screened for variability at 14 allozyme
      loci by means of horizontal starch gel. Parameters of genetic diversity, and its
      partitioning, were calculated. An indirect estimate of gene flow was based on the
      equation: Nm = (1 - GST)/4GST. KEY RESULTS: Genetic variabilities in A.
      subbaeticum and A. pertegasii were found to be the lowest known for the genus,
      the within-population genetic diversity being correlated with population size in
      both species. The distribution of genetic diversity is strikingly different among
      species, with 85 % of the total variation distributed among populations in A.
      subbaeticum, 6 % in A. pertegasii and 23 % in A. pulverulentum. Estimated levels
      of gene flow were negligible for A. subbaeticum (0.04), high for A. pertegasii
      (3.92), and substantial for A. pulverulentum (0.83). Genetic and geographic
      distances were negatively correlated in A. pertegasii, whereas no significant
      correlation was found in the other two species. CONCLUSIONS: Levels of total
      genetic diversity agree with the hypothesis that species with small total
      population size have lower levels of genetic variability than those with bigger
      ones. Strategies for the conservation of the species are recommended, such as
      preservation of natural populations and avoidance of possible causes of threat,
      as well as ex situ preservation of seeds, reinforcement of small populations of
      A. subbaeticum with plants or seeds from the same population, and avoidance of
      translocations among populations.

PMID- 15477233
TI  - Oral chronic ethanol administration to rodents by agar gel diet.
AB  - BACKGROUND: Chronic ethanol administration to rodents requires specially designed
      equipment and is labor intensive. Here we report a new procedure. METHOD: A
      commercial liquid diet preparation was made into a gel by addition of 0.5% agar.
      The gel, containing 5.3% ethanol, was offered in Falcon tubes equipped with a
      feeding opening. RESULTS: The gel consumption by C57/Bl mice resulted in high
      blood ethanol levels (average 43 mM). After 6 weeks, marked liver steatosis and
      significantly increased serum alanine aminotransferase levels had developed.
      CONCLUSIONS: Administration of ethanol in a nutritionally adequate gel provides a
      simple method for studies on chronic ethanol effects in rodents.

PMID- 15477234
TI  - Next day effects of a normal night's drinking on memory and psychomotor
      performance.
AB  - AIM: To investigate in social drinkers the effects of a 'normal' evening of
      drinking alcohol on cognitive performance. METHODS: Aiming for ecological
      validity, the study required participants to consume their usual quantity of any
      type of alcoholic beverage in their chosen company (hangover situation). However,
      the timing of drinking was restricted to the period between 22:00 and 02:00 hours
      on the night before testing. Testing included memory and psychomotor performance
      tests; testing was also performed after an evening of abstinence (no hangover
      situation), following a counterbalanced design using repeated measures, with time
      of testing (09:00, 11:00 and 13:00 hours) and order of testing (hangover/no
      hangover; no hangover/hangover) as 'between participant' factors in the analysis.
      RESULTS: Forty-eight social drinkers (33 women, 15 men) aged between 18 and 43
      years were tested, with a 1-week interval between test sessions. The morning
      after alcohol (mean consumption: 14.7 units for men; 10.4 units for women), free
      recall was impaired at 09:00 hours and delayed recognition and psychomotor
      performance were impaired throughout the morning, despite blood alcohol levels of
      zero or very near zero. CONCLUSION: Memory and psychomotor performance is
      impaired on the morning after heavy 'social' drinking.

PMID- 15477279
TI  - Formaldehyde exposure and leukaemia.

PMID- 15477280
TI  - Exposure to cobalt in the production of cobalt and cobalt compounds and its
      effect on the heart.
AB  - AIMS: To investigate whether exposure to cobalt in cobalt plants has any
      measurable effect on the cardiovascular system. METHODS: Occupational, cross
      sectional study, using a self administered questionnaire, blood pressure
      measurement, electrocardiography, and laboratory tests in which 203 male workers
      with at least one year of exposure to cobalt and 94 unexposed controls
      participated. Echocardiography was performed on a subset of 122 most highly
      exposed cobalt workers, of which 109 were analysed, and on 60 controls, of which
      57 were analysed. Analysis of covariance and a multiple regression analysis were
      used to evaluate the data. RESULTS: Two of the echocardiography parameters
      measured were associated with cobalt exposure. In the higher exposure group the
      left ventricular isovolumic relaxation time (mean 53.3, 49.1, and 49.7 ms in the
      high exposure, low exposure, and control groups respectively) and the
      deceleration time of the velocity of the early rapid filling wave (mean 194.3,
      180.5, and 171.7 ms for those in the high exposure, low exposure, and control
      groups respectively) were prolonged, indicating altered left ventricular
      relaxation and early filling. CONCLUSION: Cumulative exposure to cobalt was found
      to be associated with the results of Doppler echocardiography measurements,
      indicating altered diastole. This finding supports the hypothesis that cobalt
      accumulation in the myocardium could affect myocardial function. Whether this
      finding has clinical implications remains to be evaluated.

PMID- 15477281
TI  - Do factors in the psychosocial work environment mediate the effect of
      socioeconomic position on the risk of myocardial infarction? Study from the
      Copenhagen Centre for Prospective Population Studies.
AB  - AIM: To investigate whether the effect of socioeconomic position on risk of
      myocardial infarction (MI) is mediated by differential exposure or differential
      susceptibility to psychosocial work environment. METHODS: Data were used from
      three prospective population studies conducted in Copenhagen. A total of 16 214
      employees, 44% women, aged 20-75 years, with initial examination between 1974 and
      1992 were followed until 1996 for incident (hospital admission or death) MI.
      Register based information on job categories was used. Psychosocial job exposures
      were measured indirectly by means of a job exposure matrix based on the Danish
      Work Environment Cohort Study 1990. RESULTS: During follow up, 731 subjects were
      diagnosed with an MI: 610 men and 121 women (35% fatal). The hazards by
      socioeconomic position showed a graded effect with a hazard ratio (HR) of 1.57
      (95% CI 1.23 to 2.03) for unskilled workers compared to executive managers.
      Despite a strong and graded association in risk of MI related to decision
      authority and skill discretion, only skill discretion mediated the effect of
      socioeconomic position. The HR for unskilled workers was reduced to 1.47 (0.93 to
      2.31) after adjustment for decision authority and other cardiovascular risk
      factors, and to 1.07 (0.72 to 1.60) after adjustment for skill discretion and
      cardiovascular risk factors. No sign of synergy was found. CONCLUSIONS: Decision
      authority and skill discretion were strongly related to socioeconomic position;
      and the effect on risk of MI was partially mediated by skill discretion.
      Improvements in psychosocial work environment, especially possibilities for skill
      discretion, might contribute to reducing the incidence of MI and social
      inequality in MI.

PMID- 15477282
TI  - Contrasting patterns of mortality and hospital admissions during hot weather and
      heat waves in Greater London, UK.
AB  - BACKGROUND: Epidemiological research has shown that mortality increases during
      hot weather and heat waves, but little is known about the effect on non-fatal
      outcomes in the UK. AIMS AND METHODS: The effects of hot weather and heat waves
      on emergency hospital admissions were investigated in Greater London, UK, for a
      range of causes and age groups. Time series analyses were conducted of daily
      emergency hospital admissions, 1 April 1994 to 31 March 2000, using
      autoregressive Poisson models with adjustment for long term trend, season, day of
      week, public holidays, the Christmas period, influenza, relative humidity, air
      pollution (ozone, PM10), and overdispersion. The effects of heat were modelled
      using the average of the daily mean temperature over the index and previous two
      days. RESULTS: There was no clear evidence of a relation between total emergency
      hospital admissions and high ambient temperatures, although there was evidence
      for heat related increases in emergency admissions for respiratory and renal
      disease, in children under 5, and for respiratory disease in the 75+ age group.
      During the heat wave of 29 July to 3 August 1995, hospital admissions showed a
      small non-significant increase: 2.6% (95% CI -2.2 to 7.6), while daily mortality
      rose by 10.8% (95% CI 2.8 to 19.3) after adjusting for time varying confounders.
      CONCLUSIONS: The impact of hot weather on mortality is not paralleled by similar
      magnitude increases in hospital admissions in the UK, which supports the
      hypothesis that many heat related deaths occur in people before they come to
      medical attention. This has evident implications for public health, and merits
      further enquiry.

PMID- 15477283
TI  - Predictors of hearing threshold levels and distortion product otoacoustic
      emissions among noise exposed young adults.
AB  - AIM: To examine the relations between noise exposure and other risk factors with
      hearing function as measured by audiometric thresholds and distortion product
      otoacoustic emissions. METHODS: A total of 456 subjects were studied (393
      apprentices in construction trades and 63 graduate students). Hearing and
      peripheral auditory function were quantified using standard, automated threshold
      audiometry, tympanometry, and distortion product otoacoustic emissions (DPOAEs).
      The analysis addressed relations of noise exposure history and other risk factors
      with hearing threshold levels (HTLs) and DPOAEs at the baseline test for the
      cohort. RESULTS: The cohort had a mean age of 27 (7) years. The construction
      apprentices reported more noise exposure than students in both their occupational
      and non-occupational exposure histories. A strong effect of age and years of work
      in construction was observed at 4, 6, and 8 kHz for both HTLs and DPOAEs. Each
      year of construction work reported prior to baseline was associated with a 0.7 dB
      increase in HTL or 0.2 dB decrease DPOAE amplitude. Overall, there was a very
      similar pattern of effects between the HTLs and DPOAEs. CONCLUSIONS: This
      analysis shows a relatively good correspondence between the associations of noise
      exposures and other risk factors with DPOAEs and the associations observed with
      pure-tone audiometric thresholds in a young adult working population. The results
      provide further evidence that DPOAEs can be used to assess damage to hearing from
      a variety of exposures including noise. Clarifying advantages of DPOAEs or HTLs
      in terms of sensitivity to early manifestations of noise insults, or their
      utility in predicting future loss in hearing will require longitudinal follow up.

PMID- 15477284
TI  - Daily variation in fine and ultrafine particulate air pollution and urinary
      concentrations of lung Clara cell protein CC16.
AB  - BACKGROUND: Daily variations in ambient particulate air pollution have been
      associated with respiratory mortality and morbidity. AIMS: To assess the
      associations between urinary concentration of lung Clara cell protein CC16, a
      marker for lung damage, and daily variation in fine and ultrafine particulate air
      pollution. METHODS: Spot urinary samples (n = 1249) were collected biweekly for
      six months in subjects with coronary heart disease in Amsterdam, Netherlands (n =
      37), Erfurt, Germany (n = 47), and Helsinki, Finland (n = 47). Ambient
      particulate air pollution was monitored at a central site in each city. RESULTS:
      The mean 24 hour number concentration of ultrafine particles was 17.3x10(3) cm(
      3) in Amsterdam, 21.1x10(3) cm(-3) in Erfurt, and 17.0x10(3) cm(-3) in Helsinki.
      The mean 24 hour PM2.5 concentrations were 20, 23, and 13 microg/m3,
      respectively. Daily variation in ultrafine particle levels was not associated
      with CC16. In contrast, CC16 concentration seemed to increase with increasing
      levels of PM2.5 in Helsinki, especially among subjects with lung disorders. No
      clear associations were observed in Amsterdam and Erfurt. In Helsinki, the CC16
      concentration increased by 20.2% (95% CI 6.9 to 33.5) per 10 microg/m3 increase
      in PM2.5 concentration (lag 2). The respective pooled effect estimate was 2.1%
      (95% CI -1.3 to 5.6). CONCLUSION: The results suggest that exposure to
      particulate air pollution may lead to increased epithelial barrier permeability
      in lungs.

PMID- 15477285
TI  - Decreased fecundity among male lead workers.
AB  - AIMS: To investigate time to pregnancy (TTP) in male lead workers in order to
      determine the dose-response relation between blood lead and decreased fecundity.
      METHODS: A total of 163 currently employed married male lead battery workers were
      classified into five categories of exposure based on questionnaire information
      and annual individual blood lead measurement. Information pertaining to the TTP
      was collected using personal interviews with 133 men and their spouses, with 280
      valid pregnancies. The fecundability ratios (FRs) were calculated with the Cox
      discrete proportional hazard regression technique to evaluate the effects of lead
      exposure. RESULTS: After other factors associated with TTP were controlled for,
      there was a dose-response relation between blood lead level and TTP. The measured
      FRs were 0.90 (95% CI 0.61 to 1.34), 0.72 (0.46 to 1.11), 0.52 (0.35 to 0.77),
      and 0.40 (0.27 to 0.59) for concurrent blood lead levels of <20, 20-29, 30-39,
      and > or =40 microg/dl, respectively. Paired self comparison was also performed
      for 41 couples that had pregnancies prior to lead exposure and pregnancies with
      male occupational lead exposure. The TTP was prolonged for 0.15 cycles by a 1
      microg/dl increase in blood lead. CONCLUSIONS: These results corroborate the
      hypothesis that a raised blood lead level affects fecundity. A blood lead level
      of less than 40 microg/dl may still significantly prolong TTP.

PMID- 15477286
TI  - An occupational health intervention programme for workers at risk for early
      retirement; a randomised controlled trial.
AB  - AIMS: To evaluate an occupational health intervention programme for workers at
      risk for early retirement. METHODS: Between April 1997 and May 1998, 116
      employees of a large company who were older than 50 years indicated that they
      would not be able to work up to their retirement. They were randomly assigned to
      an intervention (n = 61) or control group (n = 55). The intervention programme
      lasted six months and was executed by an occupational physician. Job position and
      number of sick leave days after two years were collected from the company's
      computer database. A questionnaire was sent to the employees at baseline, after
      six months, and after two years; it included the Work Ability Index, the Utrecht
      Burn Out Scale, and the Nottingham Health Profile measuring quality of life.
      RESULTS: Fewer employees (11%) in the intervention group retired early than in
      the control group (28%). The total average number of sick leave days in two years
      was 82.3 for the intervention group and 107.8 for the control group. Six months
      after baseline, employees in the intervention group had better work ability, less
      burnout, and better quality of life than employees in the control group. Two
      years after randomisation no differences between the two groups were found.
      CONCLUSIONS: This occupational health intervention programme proved to be a
      promising intervention in the prevention of early retirement.

PMID- 15477287
TI  - The impact of exposure categorisation for grouped analyses of cohort data.
AB  - BACKGROUND: Poisson regression is routinely used in occupational and
      environmental epidemiology. For typical Poisson regression analyses, person-time
      and events are tabulated by categorising predictor variables that were originally
      measured on a continuous scale. In order to estimate a dose-response trend, a
      researcher must decide how to categorise exposures and how to assign scores to
      exposure groups. AIMS: To investigate the impact on regression results of
      decisions about exposure categorisation and score assignment. METHODS: Cohort
      data were generated by Monte Carlo simulation methods. Exposure categories were
      defined by quintiles or deciles of the exposure distribution. Scores were
      assigned to exposure groups based on category midpoint and mean exposure levels.
      Estimated exposure-disease trends derived via Poisson regression were compared to
      the "true" association specified for the simulation. RESULTS: Under the
      assumption that exposures conform to a lognormal or exponential distribution,
      trend estimates tend to be negatively biased when scores are assigned based on
      category midpoints and positively biased when scores are assigned based on cell
      specific mean values. The degree of bias was greater when exposure categories
      were defined by quintiles of the exposure distribution than when categories were
      defined by deciles of the exposure distribution. CONCLUSIONS: The routine
      practice of exposure categorisation and score assignment introduces exposure
      misclassification that may be differential with respect to disease status and,
      consequently, lead to biased exposure-disease trend estimates. When using the
      Poisson regression method to evaluate exposure-disease trends, such problems can
      be minimised (but not necessarily eliminated) by forming relatively refined
      exposure categories based on percentiles of the exposure distribution among
      cases, and by assigning scores to exposure categories that reflect person-time
      weighted mean exposure levels.

PMID- 15477288
TI  - A cross-sectional study of triallate exposure and neurological health among
      workers at a pesticide manufacturing and formulating facility.
AB  - AIMS: To evaluate the relation between an indicator of cumulative exposure to
      triallate and selected measures of neurological function, including nerve
      conduction, the prevalence of certain neurological deficits as determined by a
      medical examination, and vibration perception threshold testing in workers at a
      pesticide manufacturing plant. METHODS: Subjects were 50 workers with high
      estimated triallate exposure ("high triallate" group) and 50 workers with no or
      low triallate exposure ("no/low triallate" group). Industrial hygienists used
      existing work histories and personal knowledge of plant operations to develop a
      triallate score. In-person interviews elicited information on past medical
      history and on occupational and non-occupational exposures. A neurologist carried
      out nerve conduction tests of the sural and the peroneal nerves, a standardised
      neurological examination, and vibration sensation testing. RESULTS: Differences
      between the high and the no/low triallate groups were minimal for all but one of
      the six nerve conduction tests, for the prevalence of neurological abnormalities,
      and for vibration sensation perception. The high triallate group had lower mean
      sural nerve peak amplitude than the no/low triallate group (11.7 v 15.2 microV, p
      = 0.03). This difference was reduced when adjusted for other potential risk
      factors (12.5 v 14.5 microV, p = 0.25) and was not associated with cumulative
      triallate score. We also noted several associations between factors other than
      triallate and nerve conduction measures. CONCLUSION: The results were consistent
      with the absence of an association between triallate and measures of neurological
      function.

PMID- 15477289
TI  - Use of a crop and job specific exposure matrix for estimating cumulative exposure
      to triazine herbicides among females in a case-control study in the Central
      Valley of California.
AB  - AIMS: To determine if a job exposure matrix (JEM) could be developed using the
      California Department of Pesticide Regulation Pesticide Usage Database in
      conjunction with crop, time, and county specific self reported work history and
      to determine if this was a feasible method to obtain exposure estimates to
      triazine herbicides. METHODS: Agricultural work histories were gathered from
      women enrolled in a population based case-control study of ovarian cancer cases
      and random controls. The work histories were used in conjunction with the
      database to construct job exposure matrices which took into account weightings
      for job type, work location, and crop. RESULTS: Cumulative exposure estimates
      were determined for 98 study subjects. Mean exposure estimates were similar for
      cases and controls. The exposure estimates were robust and insensitive to varying
      job weight assumptions. The estimates from the original weights were highly
      correlated with those constructed using the conservative and maximum weights.
      Estimates from all three schemes produced similar multivariate age adjusted odds
      ratios comparing cases and controls. There was a high degree of agreement in
      categorised quartiles of exposure between the original and conservative, and
      original and maximum weights. CONCLUSIONS: The exposure estimate from the JEM
      provides a ranking of exposure within the study population that can be utilised
      as an "exposure score" with which to compare groups. Although it is not an
      absolute exposure measurement, it does offer a substantial advance over
      dichotomous categories based on self report of herbicide use, particularly when
      subjects are unlikely to recall specific names and dates of use of herbicides.

PMID- 15477291
TI  - Regional treatment of metastasis: surgery of colorectal liver metastases.

PMID- 15477292
TI  - Regional treatment of metastasis: role of regional perfusion. State of the art
      isolated limb perfusion for limb salvage.

PMID- 15477293
TI  - Regional treatment of metastasis: role of radiosurgery in brain metastases--gamma
      knife radiosurgery.

PMID- 15477294
TI  - Hereditary cancer: guidelines in clinical practice--general overview.

PMID- 15477295
TI  - Hereditary cancer: guidelines in clinical practice. Colorectal cancer genetics.

PMID- 15477297
TI  - Hereditary cancer: guidelines in clinical practice. Breast and ovarian cancer
      genetics.

PMID- 15477298
TI  - Exosomes for cancer immunotherapy.

PMID- 15477299
TI  - Dendritic cell-based vaccines in cancer immunotherapy: an update on clinical and
      immunological results.

PMID- 15477300
TI  - Anticancer vaccination strategies.

PMID- 15477301
TI  - Genomics and proteomics: expression arrays in clinical oncology.

PMID- 15477302
TI  - Proteomics in cancer.

PMID- 15477303
TI  - Controversies in the adjuvant treatment of breast cancer: the role of taxanes.

PMID- 15477304
TI  - Pharmacogenomics and colorectal cancer.

PMID- 15477305
TI  - Role of surgery as primary treatment and as intervention in the multidisciplinary
      treatment of soft tissue sarcoma.

PMID- 15477306
TI  - Radiation therapy in the management of adult soft tissue sarcomas.

PMID- 15477307
TI  - Systemic therapy of soft tissue sarcoma: an improvement in outcome.

PMID- 15477308
TI  - Taking care of the terminally ill cancer patient: delirium as a symptom of
      terminal disease.

PMID- 15477309
TI  - Taking care of the terminally ill cancer patient: management of gastrointestinal
      symptoms in patients with advanced cancer.

PMID- 15477310
TI  - Taking care of the terminally ill cancer patient: the communication compass--a
      model for communication in oncology.

PMID- 15477311
TI  - Molecular targeting: targeting angiogenesis in solid tumors.

PMID- 15477312
TI  - Molecular targeting: new therapeutic strategies to improve tumour apoptosis.

PMID- 15477313
TI  - Controversies in the adjuvant treatment of breast cancer: new adjuvant endocrine
      treatment strategies.

PMID- 15477315
TI  - Cancer prevention: a worldwide overview.

PMID- 15477314
TI  - Molecular targeting: PI3 kinase pathway.

PMID- 15477316
TI  - Role of prevention: cost-effectiveness of prevention.

PMID- 15477317
TI  - Cancer prevention in the political arena: the WHO perspective.

PMID- 15477318
TI  - Fertility and reproduction after chemotherapy of adult cancer patients: malignant
      lymphoma and testicular cancer.

PMID- 15477319
TI  - Head and neck cancer.

PMID- 15477320
TI  - Hormone replacement and breast cancer.

PMID- 15477321
TI  - Impact of quality of life measurement in daily clinical practice.

PMID- 15477322
TI  - Importance of microsatellite instability (MSI) in colorectal cancer: MSI as a
      diagnostic tool.

PMID- 15477323
TI  - The diagnostic and therapeutic management of leptomeningeal carcinomatosis.

PMID- 15477324
TI  - Management of neuroendocrine tumours.

PMID- 15477325
TI  - Oncological emergencies.

PMID- 15477327
TI  - Prostate cancer management.

PMID- 15477328
TI  - Role of dose in the treatment of breast cancer.

PMID- 15477329
TI  - Radiofrequency ablation in liver tumours.

PMID- 15477330
TI  - Current treatment of renal cell carcinoma.

PMID- 15477331
TI  - Opportunistic infections in patients with cancer.

PMID- 15477333
TI  - Current controversies in the adjuvant therapy of colon cancer.

PMID- 15477334
TI  - Current perspectives in the treatment of metastatic colorectal cancer.

PMID- 15477337
TI  - Screening and diagnosis of NSCLC.

PMID- 15477336
TI  - Targeted therapy in advanced colon cancer: the role of new therapies.

PMID- 15477338
TI  - The role of chemoradiotherapy in the treatment of stage III non-small-cell lung
      cancer.

PMID- 15477340
TI  - Twenty-five years of treating advanced NSCLC: what have we achieved?

PMID- 15477341
TI  - Oesophageal cancer: preoperative chemotherapy.

PMID- 15477343
TI  - Esophageal cancer: preoperative or definitive chemoradiation.

PMID- 15477344
TI  - Esophageal cancer: chemotherapy as palliative therapy.

PMID- 15477345
TI  - The cytomegalovirus m155 gene product subverts natural killer cell antiviral
      protection by disruption of H60-NKG2D interactions.
AB  - Natural killer (NK) cells are an important early mediator of host immunity to
      murine cytomegalovirus (MCMV) infection. However, MCMV has evolved mechanisms to
      elude recognition and clearance by NK cells. We have identified an MCMV immune
      evasion protein that impairs NKG2D-mediated NK cell antiviral activity. Infection
      of BALB/c 3T3 cells with the Smith strain of MCMV resulted in strong down
      regulation of H60, a high affinity ligand for NKG2D, from the surface of virus
      infected cells. The MCMV m155 protein specifically down-regulated H60 without
      affecting expression of the other known NKG2D ligands, RAE-1 and MULT-1.
      Treatment with the proteasome inhibitors lactacystin or epoxomicin reversed m155
      down-regulation of H60. An MCMV mutant virus lacking m155 was severely attenuated
      in BALB/c mice; however, treatment with neutralizing anti-NKG2D monoclonal
      antibody or with NK-depleting anti-asialo GM1 antisera restored virulence of the
      mutant virus. Thus, down-regulation of H60 by m155 is a powerful mechanism of
      inhibiting NKG2D-mediated antiviral function.

PMID- 15477346
TI  - CD24 expression on T cells is required for optimal T cell proliferation in
      lymphopenic host.
AB  - It is well established that T lymphocytes undergo homeostatic proliferation in
      lymphopenic environment. The homeostatic proliferation requires recognition of
      the major histocompatibility complex on the host. Recent studies have
      demonstrated that costimulation-mediated CD28, 4-1BB, and CD40 is not required
      for T cell homeostatic proliferation. It has been suggested that homeostatic
      proliferation is costimulation independent. Here, we report that T cells from
      mice with a targeted mutation of CD24 have a remarkably reduced rate of
      proliferation when adoptively transferred into syngeneic lymphopenic hosts. The
      reduced proliferation cannot be attributed to abnormal survival and homing
      properties of the CD24-deficient T cells. T cell proliferation in allogeneic
      hosts is less affected by this mutation. These results demonstrate a novel
      function of CD24 expressed on T cells. Thus, although distinct costimulatory
      molecules are involved in antigen-driven proliferation and homeostatic
      proliferation, both processes can be modulated by costimulatory molecules.

PMID- 15477347
TI  - ADAP-SLP-76 binding differentially regulates supramolecular activation cluster
      (SMAC) formation relative to T cell-APC conjugation.
AB  - T cell-APC conjugation as mediated by leukocyte function-associated antigen-1
      (LFA-1)-intercellular adhesion molecule (ICAM)-1 binding is followed by formation
      of the supramolecular activation cluster (SMAC) at the immunological synapse. The
      intracellular processes that regulate SMAC formation and its influence on T cell
      function are important questions to be addressed. Here, using a mutational
      approach, we demonstrate that binding of adaptor adhesion and degranulation
      promoting adaptor protein (ADAP) to SLP-76 differentially regulates peripheral
      SMAC (pSMAC) formation relative to conjugation. Although mutation of the YDDV
      sites (termed M12) disrupted SLP-76 SH2 domain binding and prevented the ability
      of ADAP to increase conjugation and LFA-1 clustering, M12 acted selectively as a
      dominant negative (DN) inhibitor of pSMAC formation, an effect that was
      paralleled by a DN effect on interleukin-2 production. ADAP also colocalized with
      LFA-1 at the immunological synapse. Our findings identify ADAP-SLP-76 binding as
      a signaling event that differentially regulates SMAC formation, and support a
      role for SMAC formation in T cell cytokine production.

PMID- 15477348
TI  - Negative regulation of mast cell signaling and function by the adaptor LAB/NTAL.
AB  - Engagement of the Fcepsilon receptor I (FcepsilonRI) on mast cells and basophils
      initiates signaling pathways leading to degranulation. Early activation events
      include tyrosine phosphorylation of two transmembrane adaptor proteins, linker
      for activation of T cells (LAT) and non-T cell activation linker (NTAL; also
      called LAB; a product of Wbscr5 gene). Previous studies showed that the secretory
      response was partially inhibited in bone marrow-derived mast cells (BMMCs) from
      LAT-deficient mice. To clarify the role of NTAL in mast cell degranulation, we
      compared FcepsilonRI-mediated signaling events in BMMCs from NTAL-deficient and
      wild-type mice. Although NTAL is structurally similar to LAT, antigen-mediated
      degranulation responses were unexpectedly increased in NTAL-deficient mast cells.
      The earliest event affected was enhanced tyrosine phosphorylation of LAT in
      antigen-activated cells. This was accompanied by enhanced tyrosine
      phosphorylation and enzymatic activity of phospholipase C gamma1 and
      phospholipase C gamma2, resulting in elevated levels of inositol 1,4,5
      trisphosphate and free intracellular Ca2+. NTAL-deficient BMMCs also exhibited an
      enhanced activity of phosphatidylinositol 3-OH kinase and Src homology 2 domain
      containing protein tyrosine phosphatase-2. Although both LAT and NTAL are
      considered to be localized in membrane rafts, immunogold electron microscopy on
      isolated membrane sheets demonstrated their independent clustering. The combined
      data show that NTAL is functionally and topographically different from LAT.

PMID- 15477349
TI  - Combinations of maternal KIR and fetal HLA-C genes influence the risk of
      preeclampsia and reproductive success.
AB  - Preeclampsia is a serious complication of pregnancy in which the fetus receives
      an inadequate supply of blood due to failure of trophoblast invasion. There is
      evidence that the condition has an immunological basis. The only known
      polymorphic histocompatibility antigens on the fetal trophoblast are HLA-C
      molecules. We tested the idea that recognition of these molecules by killer
      immunoglobulin receptors (KIRs) on maternal decidual NK cells is a key factor in
      the development of preeclampsia. Striking differences were observed when these
      polymorphic ligand: receptor pairs were considered in combination. Mothers
      lacking most or all activating KIR (AA genotype) when the fetus possessed HLA-C
      belonging to the HLA-C2 group were at a greatly increased risk of preeclampsia.
      This was true even if the mother herself also had HLA-C2, indicating that neither
      nonself nor missing-self discrimination was operative. Thus, this interaction
      between maternal KIR and trophoblast appears not to have an immune function, but
      instead plays a physiological role related to placental development. Different
      human populations have a reciprocal relationship between AA frequency and HLA-C2
      frequency, suggesting selection against this combination. In light of our
      findings, reproductive success may have been a factor in the evolution and
      maintenance of human HLA-C and KIR polymorphisms.

PMID- 15477352
TI  - Microscopic vasectomy reversal 30 years later: a summary of 4010 cases by the
      same surgeon.

PMID- 15477350
TI  - Positive and negative regulation of FcepsilonRI-mediated signaling by the adaptor
      protein LAB/NTAL.
AB  - Linker for activation of B cells (LAB, also called NTAL; a product of wbscr5
      gene) is a newly identified transmembrane adaptor protein that is expressed in B
      cells, NK cells, and mast cells. Upon BCR activation, LAB is phosphorylated and
      interacts with Grb2. LAB is capable of rescuing thymocyte development in LAT
      deficient mice. To study the in vivo function of LAB, LAB-deficient mice were
      generated. Although disruption of the Lab gene did not affect lymphocyte
      development, it caused mast cells to be hyperresponsive to stimulation via the
      FcepsilonRI, evidenced by enhanced Erk activation, calcium mobilization,
      degranulation, and cytokine production. These data suggested that LAB negatively
      regulates mast cell function. However, mast cells that lacked both linker for
      activation of T cells (LAT) and LAB proteins had a more severe block in
      FcepsilonRI-mediated signaling than LAT(-/-) mast cells, demonstrating that LAB
      also shares a redundant function with LAT to play a positive role in FcepsilonRI
      mediated signaling.

PMID- 15477353
TI  - Who's your daddy?

PMID- 15477354
TI  - Raising standards in semen analysis: professional and personal responsibility.

PMID- 15477356
TI  - Becoming piled higher and deeper.

PMID- 15477355
TI  - Management of testicular rupture in the nonacute setting--explore or observe?

PMID- 15477357
TI  - Feasibility of simultaneous testicular microdissection for sperm retrieval and
      ipsilateral testicular tumor resection in azoospermic men.

PMID- 15477358
TI  - Spermatogenic cycle length and spermatogenic efficiency in the gerbil (Meriones
      unguiculatus).
AB  - The gerbil (Meriones unguiculatus) is a rodent native of the arid regions of
      Mongolia and China. Because the gerbil can be easily bred in laboratory
      conditions, this species has been largely used as an experimental model in
      biomedical research. However, there is still little information concerning the
      testis structure and function in the gerbil. In this regard, we performed a
      detailed morpho-functional analysis of the gerbil testis and estimated the
      spermatogenic cycle length utilizing 3H-thymidine as a marker for germ cell
      progression during their evolution through the spermatogenic process. The stage
      frequencies of the XII stages characterized according to the acrosome formation
      and development were (I-XII) 13.8, 10.1, 8.1, 7.8, 4.0, 11.2, 7.5, 7.1, 5.9, 7.6,
      8.1, and 8.9. The mean duration of each seminiferous epithelium cycle was
      determined to be 10.6 +/- 1.0 days and the total duration of spermatogenesis,
      based on 4.5 cycles, was approximately 47.5 days. The volume density of tubular
      and interstitial compartments was approximately 92% and 8%, respectively. Based
      on the volume occupied by seminiferous tubules in the testis and the tubular
      diameter, about 9 and 18 m of seminiferous tubules were found per testis and per
      gram of testis, respectively. Twelve primary spermatocytes were formed from each
      type A1 spermatogonia. The meiotic index was 2.8, indicating that 30% of cell
      loss occurs during meiosis. The number of Leydig and Sertoli cells per gram of
      the testis was 28 million and each Sertoli cell was able to support approximately
      13 spermatids. The daily sperm production per gram of testis (spermatogenic
      efficiency) was 33 million. Taken together, these data indicate that, mainly due
      to the high seminiferous tubule volume density and Sertoli cell support capacity
      for germ cells, the gerbil presents high spermatogenic efficiency compared with
      other mammalian species already investigated. The data obtained in the present
      study might provide the basis for future research involving the reproductive
      biology in this species.

PMID- 15477359
TI  - Comparison of six density gradient media for selection of cryopreserved donor
      spermatozoa.
AB  - The aim of our study was to evaluate the efficiency of 4 density gradient media
      for motile cryopreserved spermatozoa selection to Percoll (Kabi Pharmacia,
      Uppsala, Sweden) and to Puresperm (J.C.D. International Laboratory, L'Aigle,
      France). Puresperm was the new medium chosen in our laboratory in 1996 as the
      substitute for Percoll. The solutions tested were 3 colloidal silane-coated
      silica particle media (Isolate, SpermGrad-100, Sil-Select Plus) and iodixanol
      (Optiprep). Semen parameters analyzed after selection were concentration,
      motility, and morphology. Semen parameters after Puresperm gradient had similar
      values compared to Percoll. Optiprep was less efficient with a poor
      concentration. Isolate had a comparatively better concentration, but the capacity
      of selection was not satisfactory. SpermGrad-100 and Sil-Select Plus were less
      effective than Puresperm. In conclusion, Puresperm could be considered a better
      alternative to Percoll for cryopreserved spermatozoa migration.

PMID- 15477360
TI  - Molecular cloning of rat Spergen-3, a spermatogenic cell-specific gene-3,
      encoding a novel 75-kDa protein bearing EF-hand motifs.
AB  - By use of differential display in combination with cDNA cloning approach, we
      isolated a novel rat gene designated as Spergen-3, which has an open reading
      frame of 2055-length nucleotides encoding a protein of 685 amino acids. Spergen-3
      gene is composed of 15 exons and mapped on chromosome 5q36, and its mouse
      counterpart, which shares 85.5% identity to rat Spergen-3 at the amino acid
      level, is mapped on chromosome 4E1. Spergen-3 encodes a 75-kDa soluble protein
      bearing putative 2 EF-hand motifs, proline-repeat, and a putative nuclear
      localization signal. Of the 2 EF-hand motifs in Spergen-3, the second one seems
      to match the consensus sequence. Reverse transcription-polymerase chain reaction
      analysis showed that the expression of Spergen-3 is developmentally up-regulated
      and that it is exclusively expressed in testis. In situ hybridization revealed
      that Spergen-3 mRNA was exclusively expressed in haploid spermatids, but its
      signal was weak or undetectable in spermatogonia, spermatocytes, and Sertoli
      cells as well as in interstitial cells. We interpreted these data as a potential
      role of Spergen-3, a new member of EF-hand family, in differentiation of haploid
      spermatids in testis.

PMID- 15477361
TI  - Peripheral effects of serotonin on the contractile responses of rat seminal
      vesicles and vasa deferentia.
AB  - With the central effects of serotonin (5-HT) on ejaculation having been
      relatively established, we investigated the peripheral effects of serotonin on
      the contractile responses of rat seminal vesicles and vasa deferentia. Male
      Sprague-Dawley rats were grouped on the basis of the agents administered:
      serotonin, clomipramine, or fluoxetine. The intraluminal pressures of the seminal
      vesicles and of the vasa deferentia were measured simultaneously. Control
      responses to hypogastric nerve stimulation (HNS) were recorded in each animal,
      and HNS was repeated after drug administration. Expression of the mRNAs of the 5
      hydroxytryptamine (5-HT) receptors (5-HT1A, 5-HT1B, and 5-HT2C), which have been
      suggested to be involved in the ejaculation process, were examined by
      semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR).
      Serotonergic agents resulted in the concentration-dependent inhibition of HNS
      induced seminal vesicle pressure increases (clomipramine > serotonin >
      fluoxetine). Vasal pressure responses were effectively inhibited by clomipramine
      and serotonin, but fluoxetine had no effect. No significant difference was
      observed in the relative expression levels of 5-HT1A receptor mRNA in seminal
      vesicles and in the vasa deferentia. However, the expression levels of 5-HT1B and
      5-HT2C receptor mRNAs were lower in the vasa deferentia than in the seminal
      vesicles. These in vivo and in vitro experimental results provide evidence for
      the peripheral role of 5-HT in the regulation of contractile responses of the
      seminal tract. Regional differences in the distribution of the 5-HT receptor
      subtypes of the seminal vesicles and the vasa deferentia might contribute to the
      different responses to serotonergic agents shown by these organs.

PMID- 15477362
TI  - Gene and protein profiling of the response of MA-10 Leydig tumor cells to human
      chorionic gonadotropin.
AB  - Activation of the steroidogenic machinery by peptide hormones involves a number
      of steps for transmitting signals from the plasma membrane to mitochondria in a
      spatially and temporally coordinated manner. Although key proteins mediating the
      hormonal signal have been identified, recent data suggest that the pathway might
      involve more complex protein-protein and protein-lipid interactions. Genomic and
      proteomic methods of analysis, namely the Affymetrix Murine Genome U74A v2
      GeneChip and the BD PowerBlot Western Array, were used to identify human
      chorionic gonadotropin (hCG)-induced changes in mRNA and protein of MA-10 Leydig
      tumor cells that parallel the increase seen in progesterone synthesis. To analyze
      the massive amount of data that was generated, a comprehensive protein
      information matrix summarizing the features of each gene or protein, including
      its known properties, as well as annotations derived by homology-based functional
      inference, was developed. Of the genes examined by Affymetrix array,
      approximately 79 were differentially expressed and of gene products examined by
      PowerBlot, 9 were differentially expressed (above twofold). Changes in the
      expression of selected transcripts of interest were confirmed using real-time
      quantitative polymerase chain reaction and immunoblot analyses. Collectively,
      these results indicate that hormonal regulation of steroidogenesis is a complex
      phenomenon, involving proteins that participate in various known and novel
      pathways, which are implicated in transmitting signals from the plasma membrane
      to mitochondria and nucleus.

PMID- 15477363
TI  - Identification and characterization of an antigen recognized by monoclonal
      antibody TRA 54 in mouse epididymis and vas deferens.
AB  - Spermatozoa in testicular fluid are known to have weak forward motility and
      cannot fertilize eggs. The epididymis is known to participate in sperm maturation
      leading fertilization, but little is known about the specific epididymal
      molecules involved in the modification of sperm. In this study, we characterized
      the new pattern of expression of an antigen previously identified in testicular
      germ cells by monoclonal antibody (mAb) TRA 54. This antigen is expressed in
      epididymal and vas deferens epithelial cells in mice older than 24 days but not
      during younger developmental stages. Evaluation by immunohistochemistry shows
      that antigen expression is limited to the cytoplasm of a specific cell population
      of epithelia along the epididymal regions and vas deferens of adult mice. The
      molecules synthesized and released by epididymal and vas deferens epithelia into
      their lumen seem to bind on spermatozoa moving down through the ducts. Immunoblot
      analysis showed that the molecules recognized by mAb TRA 54 in testis and
      epididymis were similar and share a common epitope involving carbohydrate
      domains. Interestingly, the antigens identified in epididymal and vas deferens
      epithelial cells were expressed independently of testicular germ cells and are
      produced in an androgen-dependent manner. Finally, the molecules recognized by
      mAb TRA 54 seem to play an important role in spermatogenesis, as well as in
      epididymal function related to spermatozoa maturation and ability to fertilize.

PMID- 15477364
TI  - Sperm motility in men with spinal cord injuries is enhanced by inactivating
      cytokines in the seminal plasma.
AB  - The goal of this study was to determine whether inactivating specific cytokines
      in seminal plasma improves sperm motility in men affected by spinal cord injury
      (SCI). For this purpose, we used monoclonal antibodies to interleukin 6 (IL6),
      interleukin 1 beta (IL1-beta), and tumor necrosis factor alpha (TNF-alpha), all 3
      cytokines having been previously detected at high concentrations in the seminal
      plasma of patients with SCI. In a group of 17 SCI men with low sperm motility
      (mean +/- SE, 20.1% +/- 3.1%), treatment with the 3 monoclonal antibodies at the
      median neutralization dose concentrations for 1.0 to 1.5 hours improved sperm
      motility in all cases. Effectiveness was higher in those specimens with a
      pretreatment sperm motility between 11% and 30% (from 19.3% +/- 1.4% to 41.9% +/-
      4.9%, P < .0002), suggesting that pretreatment sperm motility might represent an
      indicator of cell damage and, therefore, a factor that influences monoclonal
      antibody effectiveness. To the best of our knowledge, these results represent the
      first rational treatment for improving low sperm motility in these severely
      affected patients.

PMID- 15477365
TI  - A game of cat and mouse: xenografting of testis tissue from domestic kittens
      results in complete cat spermatogenesis in a mouse host.
AB  - Loss of genetic diversity because of infertility or the premature death of
      valuable individuals is a significant problem in the conservation of rare and
      endangered felid species, as well as in the maintenance of lines of cats used to
      study inherited feline and human disease. Attempts to overcome loss of genetic
      diversity have focused on freezing sperm; however, sperm cannot be collected from
      immature males. Previously, we reported completion of spermatogenesis in testis
      tissue from newborn pigs and goats grafted ectopically into host mice. The
      objective of this study was to extend the technique of testis tissue xenografting
      to the domestic cat as a model for felid species. Testes from 1- to 5-week-old
      domestic shorthaired kittens (n = 9) were cut into small fragments (about 0.5-1
      mm3 each), and up to 8 fragments were grafted under the back skin of each
      castrated immunodeficient host mouse (n = 16). Histologic examination of the
      testis xenografts was performed between 5 and 54 weeks posttransplantation. At
      the time of grafting, the seminiferous cords of the donor testis tissue contained
      only immature Sertoli cells and gonocytes. At 14 weeks after grafting, tubular
      expansion was evidently caused by the proliferation of Sertoli cells and tubular
      lumen formation. By 18 weeks after transplantation, the seminiferous epithelium
      contained spermatocytes, and by 20 weeks, round spermatids were the most advanced
      types of germ cells. By 36 weeks after transplantation, xenografts of cat testis
      tissue had completed spermatogenesis. These results demonstrate the potential of
      xenografting to achieve full spermatogenesis in testis tissue from kittens.
      Therefore, sperm production in a mouse host can provide an alternative for germ
      line preservation from immature felids where sperm cryopreservation is not an
      option.

PMID- 15477366
TI  - Intratesticular testosterone concentrations comparable with serum levels are not
      sufficient to maintain normal sperm production in men receiving a hormonal
      contraceptive regimen.
AB  - Intratesticular testosterone (ITT) is thought to play a key role in the control
      of spermatogenesis in man but is rarely measured. The purposes of this study were
      1) to examine the relationship between intratesticular fluid and serum
      testosterone (T) at baseline and during treatment with a contraceptive regimen
      known to suppress spermatogenesis and 2) to measure intratesticular fluid
      androgenic bioactivity. Seven men received 6 months of T enanthate (TE) 100 mg
      weekly intramuscularly plus levonorgestrel (LNG) 62.5 or 31.25 microg orally
      daily. Testicular fluid was obtained by percutaneous aspiration at baseline and
      during month 6. Mean luteinizing hormone (LH) was suppressed 98% from 3.79 +/-
      0.80 IU/L at baseline to 0.08 +/- 0.03 IU/L. Mean follicle stimulating hormone
      (FSH) was suppressed 97%, from 3.29 +/- 0.67 IU/L to 0.10 +/- 0.03 IU/L. Mean
      serum T levels were similar before (22.8 +/- 1.9 nmol/L) and during treatment
      (28.7 +/- 2.0 nmol/L) (P = .12). ITT (822 +/- 136 nmol/L) was approximately 40x
      higher than serum T (P < .001) at baseline. ITT was suppressed 98% during
      treatment to 13.1 +/- 4.5 nmol/L, a level similar to baseline serum T (P = .08)
      but significantly lower than on-treatment serum T (P = .01). At baseline,
      intratesticular fluid androgenic bioactivity (583 +/- 145 nmol/L) was 70% of the
      ITT concentration measured by radioimmunoassay. Intratesticular androgenic
      bioactivity was suppressed 93% to 40 +/- 22 nmol/L (P < .01) during treatment,
      but was 3x higher than ITT (13.1 +/- 4.5 nmol/L). Sperm counts declined from 65
      +/- 15 million/mL to 1.3 +/- 1.3 million/mL. In summary, TE plus LNG dramatically
      suppressed ITT (98%) and intratesticular androgenic bioactivity (93%) to levels
      approximating those in serum. ITT levels comparable with serum T were
      insufficient to support normal spermatogenesis. Intratesticular androgenic
      bioactivity was higher than ITT during treatment, suggesting that other androgens
      may be prevalent in the low-ITT environment.

PMID- 15477367
TI  - Microsurgical varicocelectomy for infertile couples with advanced female age:
      natural history in the era of ART.
AB  - Varicocele represents the most common cause of male infertility, and most reports
      indicate that varicocelectomy has a beneficial effect on male fertility and
      pregnancy outcome. Assisted reproductive technologies (ARTs) are an alternative
      to varicocelectomy for the management of couples with a varicocele. The age of
      the female partner is important in the decision-making process; however, the true
      influence of female age on pregnancy outcome following varicocelectomy or ART in
      these couples is unknown. We evaluated the outcomes of 2 cohorts of infertile men
      with a varicocele and a female partner 35 years of age or older; one group
      selected varicocelectomy and the other a nonsurgical approach. We reviewed a
      group of consecutive infertile men who underwent microsurgical varicocelectomy
      and whose partners are 35 years of age or older (n = 110). We also reviewed a
      consecutive group of men with varicoceles who elected not to have surgery and
      whose partners are 35 years of age or older (n = 94). The outcome measures
      included changes in semen parameters, pregnancy rates (assisted and unassisted),
      and use of ART. The surgical and nonsurgical groups had comparable semen
      parameters and female ages. Mean sperm concentration and motility increased
      significantly after varicocelectomy (P < .05). At a mean of 30 months follow-up,
      35% of couples in the surgical group achieved a spontaneous pregnancy and an
      additional 6% achieved a pregnancy via ART (20% of this group attempted ART). In
      the nonsurgical group, 25% achieved a spontaneous pregnancy and an additional 16%
      achieved a pregnancy with ART (40% of this group attempted ART). This study on
      the natural history of infertile men with varicocele and advanced female age
      suggests that the surgical and nonsurgical approaches offer comparable pregnancy
      outcome (combined assisted and unassisted pregnancy rates are about 40%).
      Overall, these data suggest that varicocelectomy is an acceptable option for
      couples with advanced female age, but other female factors must be considered in
      the decision-making process.

PMID- 15477368
TI  - Gene expression in prostate cancer cells treated with the dual 5 alpha-reductase
      inhibitor dutasteride.
AB  - We sought preclinical data on the cellular and molecular effects of dutasteride
      in androgen-responsive, human prostate cancer (PCa) cells to better understand
      the mechanisms of action of 5 alpha-reductase inhibition in these cells. We used
      the human prostate cancer cell line LNCaP, which exhibits most features of PCa
      cells including androgen responsiveness. Our findings show that dutasteride kills
      PCa cells in vitro; it dramatically reduced viability and proliferation and
      disrupted genes and cellular pathways involved in metabolic, cell cycle, and
      apoptotic responses besides those expected in androgen-signaling pathways.
      Microchip gene array expression analysis revealed activation of genes in the
      FasL/tumor necrosis factor alpha (TNF-alpha) apoptotic and cell-survival
      pathways, correlating with the growth and survival effects in the LNCaP cells.
      Real-time polymerase chain reaction confirmed expression level changes seen by
      microarray analysis of candidate genes such as PLA2G2A, CDK8, CASP7, MDK, and
      NKX3.1. Collectively, our findings delineate the cellular and molecular effects
      of dutasteride in androgen-responsive PCa cells in vitro and may lead to its
      better therapeutic and chemopreventive use in PCa.

PMID- 15477369
TI  - The effect of electrocoagulation on the sinusoids in the human penis.
AB  - We give an overview of patients who have undergone removal of the deep dorsal
      vein for venous grafting in treating Peyronie disease with or without a Bovie
      effect. From June 1998 to May 2002, 23 men received grafting of the deep dorsal
      vein for morphologic correction. Among them, 7 men underwent electrocoagulation
      treatment of bleeders per surgeons' customary practice during the entire
      procedure and were categorized as the electrocoagulation group. Sixteen patients
      received simple ligation of bleeding stumps, with 6-0 nylon sutures, and were
      classified as the ligation group. All were followed for satisfaction of penile
      morphology and assessed by the abridged 5-item version of the international index
      of erectile function (IIEF-5) scoring for erectile capability. In the
      electrocoagulation group, a mean preoperative IIEF-5 score of 22.5 +/- 1.6
      decreased to a mean postoperative IIEF-5 score of 17.9 +/- 4.1. Among them 2 men
      (28.6%) had sustained postoperative infection. Follow-up cavernosograms showing
      relatively poor filling are commensurate with intracavernosal fibrosis. In the
      ligation group, however, the mean IIEF-5 score was 22.3 +/- 1.9 preoperative and
      22.9 +/- 2.0 postoperative. Although there was no statistical significance
      between the 2 groups in preoperative IIEF scores, there was a significant
      difference between groups postoperatively. Application of electrocoagulation
      appears to be disadvantageous in preserving erectile tissues. A Bovie effect
      should be avoided in this erectile organ in order to preserve erectile capability
      and avoid infection.

PMID- 15477370
TI  - Electroejaculation with a foley catheter in the bladder.
AB  - Electroejaculation has been successfully used for sperm procurement in
      anejaculatory men desiring fertility. The electroejaculation procedure begins
      with complete catheterization of the bladder and instillation of an insemination
      medium into the bladder as a buffer. This step can minimize possible detrimental
      effects of urine on any retrograde ejaculate. The catheter is then removed. After
      the collection of the antegrade ejaculate, the bladder is catheterized again. Our
      objective was to evaluate the possibility of performing electroejaculation while
      the Foley catheter is instilled in the bladder. Eleven men with anejaculation
      underwent 22 procedures of rectal probe electroejaculation. Each patient
      underwent electroejaculation twice, once without the catheter instilled in the
      bladder (standard method) and once with it. The 2 methods, with and without the
      catheter, showed no significant differences in volume, concentration, motility,
      count, and total motility of the antegrade ejaculate. In retrograde ejaculate,
      there were no significant differences in the count, motility, and total motility.
      In addition, there was no difference in the total count and the total motility of
      both fractions in the 2 methods. In this study, we show that ejaculation can be
      achieved while the Foley catheter is instilled in the urethra without any
      detrimental effect on the sperm. Therefore, we recommend not removing the Foley
      catheter while performing electroejaculation.

PMID- 15477371
TI  - Restorative increases in serum testosterone levels are significantly correlated
      to improvements in sexual functioning.
AB  - It is recognized that testosterone (T) levels decrease in men with age, as does
      sexual function. We hypothesize that T supplementation in hypogonadal men with
      sexual dysfunction will restore certain elements of sexual function. Hypogonadal
      male subjects (total T < or = 300 ng/dL, n = 406, mean age 58 years) reporting
      one or more symptoms of low testosterone were randomized to T gel (50 mg/d and
      100 mg/d), T patch, or placebo. Twenty-four-hour pharmacokinetic profiles for T
      were obtained. The 3 primary end points evaluated at 30 and 90 days posttreatment
      included a significant change in the frequency of intercourse and nighttime
      erections per 7-day week as well as a change in sexual desire measured on a
      Likert-type scale and calculated as a mean daily score. At day 30, a significant
      increase from baseline in sexual desire was noted for those on 100 mg/d T gel
      compared with those on 50 mg/d T gel, T patch, or placebo (1.2 vs 0.4, 0.7, and
      0.4, respectively). A significant increase from baseline in the frequency of
      nighttime erections was also noted for those on 100 mg/d T gel compared with
      those on 50 mg/d T gel or placebo (51% of subjects in the 100 mg/d T gel group
      had an increase in frequency vs 30% for the 50 mg/d T gel group and 26% in the
      placebo group). Finally, a significant increase from baseline in the frequency of
      intercourse was evidenced for those on 100 mg/d T gel compared with those on T
      patch or placebo (39% of subjects in the 100 mg/d T gel group had an increase in
      frequency vs 21% for the T patch group and 24% in the placebo group). Similar
      results were seen for 100 mg/d T gel at day 90 for sexual desire and nighttime
      erections vs placebo. These data demonstrate a clear relationship between
      restoring serum T concentrations and improvement in certain parameters of sexual
      function. We propose that threshold T levels are needed in order to significantly
      affect improvements in sexual functioning.

PMID- 15477372
TI  - Rapid glucocorticoid mediation of suppressed testosterone biosynthesis in male
      mice subjected to immobilization stress.
AB  - Physical and psychosocial stress challenge homeostasis, increasing glucocorticoid
      secretion (in rodents, corticosterone [CORT]) while decreasing testosterone (T)
      levels. The dynamics of stress-induced changes in T, CORT, and luteinizing
      hormone (LH) concentrations in mice have not been investigated previously. In
      particular, it remains to be established whether there is a rapid effect of CORT
      that is directly mediated by glucocorticoid receptors (GRs) in the testis.
      Therefore, serum and intratesticular T, serum CORT, and LH levels were measured
      during acute immobilization (IMO) stress, using the C57BL/6 strain of mice. The
      effects of testicular GR blockade were investigated by administration of the GR
      antagonist, RU486, via intratesticular (IT) or intraperitoneal (IP) injection.
      CORT levels increased in stressed males starting at 15 minutes, reaching a
      fivefold higher plateau by 1 hour compared with controls (P < .01). Conversely,
      starting from 30 minutes on, both serum and intratesticular T levels decreased in
      stressed males to 30% and 8% of control values, respectively, by 6 hours (P <
      .01). In contrast, LH was unchanged by IMO stress for up to 6 hours.
      Intratesticular treatment with RU486 partially prevented the IMO-induced decline
      in T levels. CORT treatment reduced intracellular cyclic adenosine monophosphate
      (cAMP) content in Leydig cells by 15 minutes and T production by 30 minutes in
      vitro. We conclude that 1) the rapid changes in T suggest a suppression of T
      biosynthesis by glucocorticoid through a nongenomic mechanism, lowering the
      production of cytoplasmic cAMP; 2) changes in gonadotropic stimulation of Leydig
      cells are unlikely to explain the suppression of T levels during acute stress;
      and 3) the results are consistent with a direct inhibitory action of CORT on
      Leydig cells.

PMID- 15477373
TI  - Ram sperm selection by a dextran/swim-up procedure increases fertilization rates
      following intrauterine insemination in superovulated ewes.
AB  - The objective of this study was to compare the efficacy of 2 dextran/swim-up
      media to increase the sperm quality parameters and the maintenance of these
      parameters at 15 degrees C and 30 degrees C over 6 hours. Additionally, this
      study examined whether differences in sperm quality reflect different
      reproductive efficiencies following intrauterine insemination in superovulated
      ewes. The study involved 2 selected samples (SS) obtained by dextran/swim-up,
      performed either with (SS+) or without (SS-) capacitating compounds, and a
      control sample consisting of raw semen diluted in the same medium. The efficacies
      of the swim-up sperm selection procedures were similar in both media, and no
      significant differences were found among the evaluated parameters. Conversely, we
      found important differences between selected and control samples. Sperm motility,
      viability (as assessed by carboxifluorescein diacetate/propidium iodide [PI]
      staining), and mitochondrial activity (as assessed by rhodamine 123/PI) were
      significantly higher in the selected samples than in the control. Additionally,
      following incubation at 15 degrees C, the preservation of sperm quality was
      significantly better in the selected samples than in the control samples. After 6
      hours of incubation at 15 degrees C, selected samples had a motility value of
      46%, which was significantly (P < .001) higher than the value observed in control
      samples (27%). The percentage of viable cells observed after 6 hours of
      incubation at 15 degrees C was significantly (P < .0001) higher in selected
      samples than in the control samples. Furthermore, after 2 hours of incubation at
      30 degrees C, swim-up samples had viability values that were significantly (P <
      .0001) higher than those of the control samples. SS+ and SS- samples did not
      differ significantly in spermatozoa yield, sperm quality, or survival.
      Differences between selected samples and controls were reflected in the
      fertilization rate obtained following intrauterine insemination in superovulated
      ewes that experienced a 52-hour interval between progestagen removal and
      artificial insemination. A restricted criterion for fertilization rate evaluation
      was established, and only the percentage of embryos recovered from the uterine
      horns 6 days after insemination was considered with respect to the total number
      of corpora lutea counted in the ovaries. The fertilization rate of SS- samples
      (50%) was significantly higher (P > .001) than those of the SS+ (2%) and control
      samples (5%).

PMID- 15477374
TI  - Erectile dysfunction in smokers: a penile dynamic and vascular study.
AB  - In this study, we aimed to determine the hemodynamic mechanisms through which
      cigarette smoking, as an independent risk factor, induces erectile dysfunction
      (ED). We performed a standard ED evaluation that included history; a physical
      exam; and serum glucose, testosterone, and prolactin levels. We then excluded ED
      patients with abnormal androgen profiles and patients with ED risk factors other
      than smoking. A total of 109 ED patients entered the study, including 71 current
      smokers and 38 nonsmokers. All patients then underwent extensive evaluation,
      including nocturnal penile tumescence and rigidity (NPTR) monitoring with
      Rigiscan, followed by pharmacopenile duplex ultrasonography (PPDU) and redosing
      pharmacocavernosometry (RPC). Results of the above tests were compared in the
      smoker and nonsmoker groups. We also performed receiver operating characteristic
      (ROC) curve analysis to determine which diagnostic parameter is most affected by
      cigarette smoking. The 4 most significant variates served as input features for a
      logistic regression model, designed to predict smoking. The average age for
      smokers and nonsmokers was 44.3 and 51.2 years, respectively (P = .02). Eighty
      six percent of smokers had abnormal NPTR testing compared with 55% of nonsmokers
      (P = .02). The average peak systolic velocity (PSV) was 26.8 and 31.2 cm/s for
      smokers and nonsmokers, respectively, and this difference was not found to be
      statistically significant (P = .19) in this study. On performing RPC, an abnormal
      maintenance flow (MF) of >5 mL/min was detected in 89% of smokers and in 47% of
      nonsmokers, and the difference was significant (P < .01). With the use of smoking
      as the outcome, the ROC area of different diagnostic parameters was as follows:
      0.79 for penile base rigidity, 0.58 for PSV, and 0.77 for MF. A logistic
      regression model that used the 4 most significant variates as input features
      yielded a ROC of 0.857. The results of NPTR testing in our smoker and nonsmoker
      groups indicated that ED in smokers is mainly of organic etiology. On the basis
      of the PPDU findings and the higher incidence of abnormal MF in the smoker group
      and its relatively high ROC value, we concluded that dysfunction of penile veno
      occlusive mechanisms plays a substantial role in the development of ED in
      smokers.

PMID- 15477375
TI  - Nickel-induced oxidative stress in testis of mice: evidence of DNA damage and
      genotoxic effects.
AB  - Oxidative stress (OS) mechanisms are speculated to play a significant role in
      nickel-induced toxic effects and their carcinogenic potency. Although nickel
      induced oxidative damage in somatic tissues is well demonstrated, evidence of the
      involvement of a similar mechanism(s) in nickel-induced testicular dysfunction
      and associated genotoxic effects is scarce. Hence, the present study aimed to
      investigate the nickel-induced OS response in testis and the associated genotoxic
      implications in vivo. Initially, the toxicity profile of nickel chloride was
      determined in adult albino mice (CFT-Swiss) following administration
      (intraperitoneal) of single doses. Subsequently, multiple sublethal doses (1.25,
      2.5, and 5.0 micromol/100 g of body weight per day for 3 days) were used to
      characterize effects on testicular histoarchitecture, lipid peroxidation (LPO) in
      testis (homogenates, microsomal or mitochondrial fractions) and epididymal sperm,
      DNA damage, induction of apoptosis in testis, and incidence of sperm head
      abnormalities. Although short-term doses of nickel induced only a minimal LPO
      response, multiple doses elicited a moderate (15% to 30%) increase in LPO in
      whole homogenates and higher dose-related increases in both mitochondrial (20% to
      50%) and microsomal fractions (25% to 60%). This was associated with a
      significant increase in DNA damage in the testis as evidenced by increased single
      strand breaks (fluorimetric analysis of DNA unwinding assay). Further, at higher
      doses, nickel-induced apoptosis was demonstrable in the testis biochemically.
      Although caudal sperm counts determined at all sampling weeks showed no
      alterations, analysis for head abnormalities revealed a nearly 3- to 4-fold
      increase in the percentage of abnormal sperms among the nickel-treated males
      during the first 3 weeks. Furthermore, mating of nickel-treated (2.5 micromol/100
      g of body weight per day for 5 days) males sequentially for a period of 5 weeks
      with untreated females resulted in a significant increase in male-mediated
      dominant lethal-type mutations (the frequency of dead implantations) during the
      first 3 weeks, suggesting a stage-specific effect on postmeiotic germ cells.
      These findings suggest that testicular toxicity of nickel compounds may be
      related to enhanced production of reactive oxygen species, probably mediated
      through oxidative damage to macromolecules, including damage to DNA.

PMID- 15477376
TI  - Does seminal plasma PSP-I/PSP-II spermadhesin modulate the ability of boar
      spermatozoa to penetrate homologous oocytes in vitro?
AB  - Low concentration (0.15 mg per million of spermatozoa) of seminal plasma-derived
      PSP-I/PSP-II spermadhesin heterodimer is able to preserve the viability of highly
      extended boar spermatozoa. Whether spermatozoa also keep their fertilizing
      capacity is not yet known. The present study evaluated the effect of exposing
      freshly extended and frozen-thawed boar spermatozoa (10 million/mL) to PSP-I/PSP
      II (1.5 mg/mL) for 30 or 120 minutes on sperm characteristics and the outcome of
      in vitro penetration of immature (IM) and in vitro matured (IVM) homologous
      oocytes, aiming to identify this spermadhesin as a suitable modulator for sperm
      handling protocols. Although exposure to the heterodimer improved sperm viability
      and motility without increasing the levels of sperm acrosome exocytosis in both
      freshly extended and frozen-thawed spermatozoa, this pretreatment did not affect
      sperm penetration rates or sperm numbers per oocyte when pretreated fresh
      spermatozoa were coincubated with IM or IVM oocytes compared with controls. When
      cryopreserved spermatozoa were tested, however, on IVM oocytes, already a 30
      minute preincubation exposure to PSP-I/PSP-II showed a significant blocking
      effect on penetration rate (from 90% to 32%, P < .05) and on mean sperm numbers
      per oocyte (2.9 to 1.6, P < .05). To disclose the nature of this paradox, frozen
      thawed spermatozoa were cleansed (by centrifugation in saline bovine serum
      albumin or through Percoll density gradient separation) and the procedure
      repeated. Oocyte penetration (but not number of spermatozoa per oocyte) increased
      (P < .05) when spermatozoa were cleansed with Percoll compared with either washed
      or unwashed controls (53% vs 13% vs 31%, respectively). In addition, the
      percentages of polyspermic oocytes remained lower than control (38.5% vs 68.7%,
      respectively; P < .05). In conclusion, the results confirm that exposure of fresh
      or frozen-thawed boar spermatozoa to a low dose of seminal PSP-I/PSP-II
      spermadhesin preserves sperm viability and motility in vitro. Although there was
      no obvious influence of the heterodimer on the capability of freshly extended
      boar spermatozoa to penetrate homologous oocytes (either IM or IVM), PSP-I/PSP-II
      exerted a deleterious effect when frozen-thawed spermatozoa were used to
      penetrate IVM oocytes. Such an effect of cryopreservation seems to a certain
      extent reversible, since cleansing of the sperm surface decreased, at least
      partially, this blocking effect, increasing both penetration and the monospermic
      rates.

PMID- 15477377
TI  - An ex vivo analysis of Sertoli cell actin dynamics following gonadotropic hormone
      withdrawal.
AB  - The receptors for the steroid hormone testosterone and the peptide hormone
      follicle-stimulating hormone are localized to the somatic Sertoli cell in the
      seminiferous epithelium. In the rat, prolonged gonadotrophic hormone withdrawal
      has been shown to result in substantial germ cell apoptosis. Previous studies
      have shown that, coincident with the loss of germ cells following hypophysectomy,
      the actin cytoskeleton of the Sertoli cell becomes disorganized and diffuse
      throughout the cell's cytoplasm. The molecular mechanisms that govern Sertoli
      cell actin filament dynamics in response to the loss of gonadotrophic hormones
      remain undefined. It was therefore hypothesized that hypophysectomy brings about
      a decrease in the amount of polymerized actin (F-actin) within the Sertoli cell
      and that this decrease is associated with changes in the expression of genes
      known to govern Sertoli actin dynamics. To this end, Sertoli cells were isolated
      from adult control and hypophysectomized rats. Sertoli cells from
      hypophysectomized rats were found to contain significantly less (72%) F-actin
      relative to untreated controls, although overall, beta-actin protein and mRNA
      expression remained constant. The expression levels of genes known to directly
      influence the amount of F-actin in cells were then examined by Northern blot
      analysis. Cofilin and profilin I gene expression was unaffected by
      hypophysectomy, whereas the expression of profilin II and espin both decreased
      significantly (47% and 42%, respectively). Taken together, these results suggest
      that, following hypophysectomy, the actin cytoskeleton of the Sertoli cell shifts
      to a predominantly depolymerized state, perhaps in part because of decreases in
      profilin II and espin gene products.

PMID- 15477378
TI  - Intracellular Ca2+ regulates the phosphorylation and the dephosphorylation of
      ciliary proteins via the NO pathway.
AB  - The phosphorylation profile of ciliary proteins under basal conditions and after
      stimulation by extracellular ATP was investigated in intact tissue and in
      isolated cilia from porcine airway epithelium using anti-phosphoserine and anti
      phosphothreonine specific antibodies. In intact tissue, several polypeptides were
      serine phosphorylated in the absence of any treatment (control conditions). After
      stimulation by extracellular ATP, changes in the phosphorylation pattern were
      detected on seven ciliary polypeptides. Serine phosphorylation was enhanced for
      three polypeptides (27, 37, and 44 kD), while serine phosphorylation was reduced
      for four polypeptides (35, 69, 100, and 130 kD). Raising intracellular Ca2+ with
      ionomycin induced identical changes in the protein phosphorylation profile.
      Inhibition of the NO pathway by inhibiting either NO synthase (NOS), guanylyl
      cyclase (GC), or cGMP-dependent protein kinase (PKG) abolished the changes in
      phosphorylation induced by ATP. The presence of PKG within the axoneme was
      demonstrated using a specific antibody. In addition, in isolated permeabilized
      cilia, submicromolar concentrations of cGMP induced protein phosphorylation.
      Taken together, these results suggest that the axoneme is an integral part of the
      intracellular NO pathway. The surprising observation that ciliary activation is
      accompanied by sustained dephosphorylation of ciliary proteins via NO pathway was
      not detected in isolated cilia, suggesting that the protein phosphatases were
      either lost or deactivated during the isolation procedure. This work reveals that
      any pharmacological manipulation that abolished phosphorylation and
      dephosphorylation also abolished the enhancement of ciliary beating. Thus, part
      or all of the phosphorylated polypeptides are likely directly involved in
      axonemal regulation of ciliary beating.

PMID- 15477379
TI  - Voltage-dependent anion channel-1 (VDAC-1) contributes to ATP release and cell
      volume regulation in murine cells.
AB  - Extracellular ATP regulates several elements of the mucus clearance process
      important for pulmonary host defense. However, the mechanisms mediating ATP
      release onto airway surfaces remain unknown. Mitochondrial voltage-dependent
      anion channels (mt-VDACs) translocate a variety of metabolites, including ATP and
      ADP, across the mitochondrial outer membrane, and a plasmalemmal splice variant
      (pl-VDAC-1) has been proposed to mediate ATP translocation across the plasma
      membrane. We tested the involvement of VDAC-1 in ATP release in a series of
      studies in murine cells. First, the full-length coding sequence was cloned from a
      mouse airway epithelial cell line (MTE7b-) and transfected into NIH 3T3 cells,
      and pl-VDAC-1-transfected cells exhibited higher rates of ATP release in response
      to medium change compared with mock-transfected cells. Second, ATP release was
      compared in cells isolated from VDAC-1 knockout [VDAC-1 (-/-)] and wild-type (WT)
      mice. Fibroblasts from VDAC-1 (-/-) mice released less ATP than WT mice in
      response to a medium change. Well-differentiated cultures from nasal and tracheal
      epithelia of VDAC-1 (-/-) mice exhibited less ATP release in response to luminal
      hypotonic challenge than WT mice. Confocal microscopy studies revealed that cell
      volume acutely increased in airway epithelia from both VDAC-1 (-/-) and WT mice
      after luminal hypotonic challenge, but VDAC-1 (-/-) cells exhibited a slower
      regulatory volume decrease (RVD) than WT cells. Addition of ATP or apyrase to the
      luminal surface of VDAC-1 (-/-) or WT cultures with hypotonic challenge produced
      similar initial cell height responses and RVD kinetics in both cell types,
      suggesting that involvement of VDAC-1 in RVD is through ATP release. Taken
      together, these studies suggest that VDAC-1, directly or indirectly, contributes
      to ATP release from murine cells. However, the observation that VDAC-1 knockout
      cells released a significant amount of ATP suggests that other molecules also
      play a role in this function.

PMID- 15477380
TI  - Molecular basis of inward rectification: polyamine interaction sites located by
      combined channel and ligand mutagenesis.
AB  - Polyamines cause inward rectification of (Kir) K+ channels, but the mechanism is
      controversial. We employed scanning mutagenesis of Kir6.2, and a structural
      series of blocking diamines, to combinatorially examine the role of both channel
      and blocker charges. We find that introduced glutamates at any pore-facing
      residue in the inner cavity, up to and including the entrance to the selectivity
      filter, can confer strong rectification. As these negative charges are moved
      higher (toward the selectivity filter), or lower (toward the cytoplasm), they
      preferentially enhance the potency of block by shorter, or longer, diamines,
      respectively. MTSEA+ modification of engineered cysteines in the inner cavity
      reduces rectification, but modification below the inner cavity slows spermine
      entry and exit, without changing steady-state rectification. The data provide a
      coherent explanation of classical strong rectification as the result of polyamine
      block in the inner cavity and selectivity filter.

PMID- 15477381
TI  - Relationship of alcohol drinking pattern to risk of hypertension: a population
      based study.
AB  - Epidemiological studies have demonstrated a positive relationship between heavy
      alcohol use and hypertension, but few studies have directly addressed the role of
      drinking pattern. This study was designed to investigate the association of
      current alcohol consumption and aspects of drinking pattern with hypertension
      risk in a sample of 2609 white men and women from western New York, aged 35 to 80
      years, and free from other cardiovascular diseases. Hypertension was defined by
      systolic blood pressure > or =140 mm Hg or diastolic blood pressure > or =90 mm
      Hg or use of antihypertensive medication. Odds ratios (95% confidence intervals)
      were computed after adjustment for several covariates. Compared with lifetime
      abstainers, participants reporting drinking on a daily basis (1.75 [1.13 to
      2.72]) or mostly without food (1.64 [1.08 to 2.51]) exhibited significantly
      higher risk of hypertension. When analyses were restricted to current drinkers,
      daily drinkers and participants consuming alcohol without food exhibited a
      significantly higher risk of hypertension compared with those drinking less than
      weekly (1.65 [1.18 to 2.30]) and those drinking mostly with food (1.49 [1.10 to
      2.00]), respectively. After additional adjustment for the amount of alcohol
      consumed in the past 30 days, the results were follows: 0.90 (0.58 to 1.41) for
      daily drinkers and 1.41 (1.04 to 1.91) for drinkers without food. For predominant
      beverage preference, no consistent association with hypertension risk was found
      across the various types of beverages considered (beer, wine, and liquor). In
      conclusion, drinking outside meals appears to have a significant effect on
      hypertension risk independent of the amount of alcohol consumed.

PMID- 15477382
TI  - Magnesium inhibits norepinephrine release by blocking N-type calcium channels at
      peripheral sympathetic nerve endings.
AB  - Although Mg2+ contributes to blood pressure regulation partly in terms of
      vasodilator action, its sympatholytic effect may also play an important role to
      control blood pressure. Thus, in the present study, we investigated the effect of
      Mg2+ on sympathetic tone and blood pressure. We studied its actions on the blood
      pressure response to hydralazine, a direct vasodilator, in conscious
      spontaneously hypertensive rats (SHRs), and to electrical stimulation in the
      pithed Sprague-Dawley rat; catecholamine release by peripheral sympathetic nerve
      endings; and the N-type Ca2+ channels of cultured neural cells. Intravenous Mg2+
      infusion (MgSO4: 3x10(-6) mol/kg body weight/min) induced the greater hypotensive
      response to hydralazine with attenuated reflex tachycardia in SHRs. In pithed
      rats, Mg2+ infusion significantly attenuated the blood pressure elevation (2+/-2
      mm Hg versus 27+/-6 mm Hg, P<0.01) in response to spinal electrical stimulation.
      In the perfused mesenteric arteries system, norepinephrine release was
      significantly attenuated (51+/-2%, P<0.01) by high Mg2+ concentration solution
      (4.8 mmol/L) compared with normal Mg2+ solution (1.2 mmol/L). When we applied the
      perforated whole-cell patch clamp method to nerve growth factor-treated PC12
      cells, Mg2+ blocked voltage-gated Ca2+ currents in a concentration-dependent
      manner. The majority of the voltage-gated Ca2+ currents were carried through N
      type channels, followed by L-type channels. Mg2+ blocked both of these channels.
      These findings suggest that Mg2+ blocks mainly N-type Ca2+ channels at nerve
      endings, and thus inhibits norepinephrine release, which decreases blood pressure
      independent of its direct vasodilating action.

PMID- 15477383
TI  - Upregulation of angiotensin-converting enzyme 2 by all-trans retinoic acid in
      spontaneously hypertensive rats.
AB  - There is increasing evidence that all-trans retinoic acid (atRA) influences gene
      expression of components of renin-angiotensin system (RAS), which plays a pivotal
      role in the pathophysiology of essential hypertension. To further validate
      effects of atRA on the RAS and to assess the possibility that atRA affects the
      activity of angiotensin-converting enzyme 2 (ACE2), gene, and protein expression
      of ACE2 have been examined by real-time polymerase chain reaction and Western
      blot methods in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY)
      rats. Rats were treated with atRA (10 or 20 mg x kg(-1) x day(-1)) or placebo
      given as daily intraperitoneal injection for 1 month. ACE2 expression was
      markedly decreased in placebo-treated SHR when compared with WKY rats. However,
      in atRA-treated SHR, a significant upregulation of ACE2 expression was observed
      in heart and kidney. In conclusion, chronic atRA treatment increases gene and
      protein expressions of ACE2, resulting in the reduction of blood pressure and the
      attenuation of myocardial damage in SHR, which suggests that atRA may be an
      attractive candidate for the potential prevention and treatment of human
      essential hypertension.

PMID- 15477384
TI  - Hormone replacement therapy and cardiovascular disease: what went wrong and where
      do we go from here?
AB  - Observational studies in humans and experimental studies in animals and isolated
      cells supported the widely held belief that hormone replacement therapy protects
      the cardiovascular system from disease. To nearly everyone's astonishment, the
      Women's Health Initiative Study and the Heart and Estrogen/Progestin Replacement
      Study overturned the conclusion that hormone replacement therapy protects the
      cardiovascular system and, in fact, supported the opposite view that such therapy
      may actually increase the risk of cardiovascular disease. This review addresses 2
      questions: what went wrong and where do we go from here?

PMID- 15477385
TI  - Blood pressure and the cystic fibrosis gene: evidence for lower pressure rises
      with age in female carriers.
AB  - Individuals homozygous for the autosomal recessive disorder CF are known to have
      low blood pressure, thought to be caused by greatly increased sweat salt loss. We
      examined whether carriers of the CF gene also have low blood pressure. Our pilot
      studies had suggested an effect limited to females, leading to 2 further studies
      in white females. In the first, blood pressure was measured in 232 known CF
      mutation carriers and compared with 246 mutation-negative control subjects. The
      carriers showed a significantly lower rate of increase in systolic blood pressure
      with age than the controls, especially after age 50 (3.5% per decade compared
      with 5.4% per decade, P=0.010). In a small substudy, sweat sodium and chloride
      levels were highest in those CF carriers with the lowest blood pressures. In the
      second study, CF carrier status was investigated in 563 normotensive females and
      in 607 women with essential hypertension diagnosed to test whether a lower
      incidence of carriers in the hypertensives suggested a protective effect. Twenty
      five of the normotensives (4.4%) were carriers compared with 21 (3.5%) of the
      hypertensive group (P=0.45). Older CF carrier females had lower systolic and
      diastolic pressures than matched control subjects, with a tendency for blood
      pressure to increase less with age. This could result in significant reduction in
      stroke and heart disease. The effect on blood pressure is insufficient to prevent
      hypertension, though it remains conceivable that the severity might be
      ameliorated in carriers.

PMID- 15477386
TI  - NaCl restriction upregulates renal Slc26a4 through subcellular redistribution:
      role in Cl- conservation.
AB  - Slc26a4 (Pds, pendrin) is an anion transporter expressed in the apical region of
      type B and non-A, non-B intercalated cells of the distal nephron. It is
      upregulated by aldosterone analogues and is critical in the development of
      mineralocorticoid-induced hypertension. Thus, Slc26a4 expression and its role in
      blood pressure and fluid and electrolyte homeostasis was explored during NaCl
      restriction, a treatment model in which aldosterone is appropriately increased.
      Ultrastructural immunolocalization, balance studies, and cortical collecting
      ducts (CCDs) perfused in vitro were used. With moderate physiological NaCl
      restriction, Slc26a4 expression in the apical plasma membrane increased 2- to 3
      fold in type B intercalated cells. Because Slc26a4 transports Cl-, we tested
      whether NaCl balance differs in Slc26a4(+/+) and Slc26a4(-/-) mice during NaCl
      restriction. Cl- absorption was observed in CCDs from Slc26a4(+/+) but not from
      Slc26a4(-/-) mice. After moderate NaCl restriction, urinary volume and Cl-
      excretion were increased in Slc26a4(-/-) relative to Slc26a4(+/+) mice. Moreover,
      Slc26a4(-/-) mice had evidence of relative vascular volume depletion because they
      had a higher arterial pH, hematocrit, and blood urea nitrogen than wild-type
      mice. With moderate NaCl restriction, blood pressure was similar in Slc26a4(+/+)
      and Slc26a4(-/-) mice. However, on a severely restricted intake of NaCl, Slc26a4(
      /-) mice were hypotensive relative to wild-type mice. We conclude that Slc26a4 is
      upregulated with NaCl restriction and is critical in the maintenance of acid-base
      balance and in the renal conservation of Cl- and water during NaCl restriction.

PMID- 15477387
TI  - Identification of novel Myc target genes with a potential role in
      lymphomagenesis.
AB  - The c-Myc transcription factor regulates a wide set of genes involved in
      processes such as proliferation, differentiation and apoptosis. Therefore,
      altered expression of Myc leads to deregulation of a large number of target genes
      and, as a consequence, to tumorigenesis. For understanding Myc-induced
      transformation, identification of these target genes is essential. In this study,
      we searched for Myc target genes involved in lymphomagenesis using different
      mouse T and B cell lymphoma cell lines transformed by a conditional Myc-allele.
      Target genes obtained by microarray experiments were further subjected to a
      kinetic analysis of mRNA expression upon Myc inactivation/reactivation,
      bioinformatic examination of Myc binding sites and chromatin immunoprecipitation.
      This approach allowed us to define targets whose activation is a direct
      consequence of Myc binding. Among the 38 novel Myc targets, we identified several
      genes implicated in the tumor development. These genes are not only relevant for
      mouse lymphomas because we observed their upregulation in human lymphomas as
      well. Our findings further the understanding of Myc-induced lymphomagenesis and
      help toward developing more efficient antitumor strategies.

PMID- 15477388
TI  - A high resolution protein interaction map of the yeast Mediator complex.
AB  - Mediator is a large, modular protein complex remotely conserved from yeast to man
      that conveys regulatory signals from DNA-binding transcription factors to RNA
      polymerase II. In Saccharomyces cerevisiae, Mediator is thought to be composed of
      24 subunits organized in four sub-complexes, termed the head, middle, tail and
      Cdk8 (Srb8-11) modules. In this work, we have used screening and pair-wise two
      hybrid approaches to investigate protein-protein contacts between budding yeast
      Mediator subunits. The derived interaction map includes the delineation of
      numerous interaction domains between Mediator subunits, frequently corresponding
      to segments that have been conserved in evolution, as well as novel connections
      between the Cdk8 (Srb8-11) and head modules, the head and middle modules, and the
      middle and tail modules. The two-hybrid analysis, together with co
      immunoprecipitation studies and gel filtration experiments revealed that Med31
      (Soh1) is associated with the yeast Mediator that therefore comprises 25
      subunits. Finally, analysis of the protein interaction network within the
      Drosophila Mediator middle module indicated that the structural organization of
      the Mediator complex is conserved from yeast to metazoans. The resulting
      interaction map provides a framework for delineating Mediator structure-function
      and investigating how Mediator function is regulated.

PMID- 15477389
TI  - Conservation of adjacency as evidence of paralogous operons.
AB  - Most of the analyses on the conservation of gene order are limited to orthologous
      genes. However, the organization of genes into operons might also result in the
      conservation of gene order of paralogous genes. Thus, we sought computational
      evidence that conservation of gene order of paralogous genes represents another
      level of conservation of genes in operons. We found that pairs of genes within
      experimentally characterized operons of Escherichia coli K12 and Bacillus
      subtilis tend to have more adjacently conserved paralogs than pairs of genes at
      transcription unit boundaries. The fraction of same strand gene pairs
      corresponding to conserved paralogs averages 0.07 with a maximum of 0.22 in
      Borrelia burgdorferi. The use of evidence from the conservation of adjacency of
      paralogous genes can improve the prediction of operons in E.coli K12 by
      approximately 0.27 over predictions using conservation of adjacency of
      orthologous genes alone.

PMID- 15477390
TI  - Biochemical evidence of translational infidelity and decreased
      peptidyltransferase activity by a sarcin/ricin domain mutation of yeast 25S rRNA.
AB  - A C-->U mutation (rdn5) in the conserved sarcin/ricin domain of yeast 25S rRNA
      has been shown to cause translational suppression and paromomycin resistance. It
      also separates the killing from the misreading effect of this antibiotic. We
      confirm these findings and provide in vitro evidence that rdn5 causes a 3-fold
      increase in translational errors and resistance to paromomycin. The role of this
      25S rRNA domain in ribosome's decoding function was further demonstrated when 60S
      subunits from rdn5 cells were combined with 40S subunits from cells carrying an
      error-prone mutation in the eukaryotic accuracy center ribosomal protein S23, an
      homologue of Escherichia coli S12. These hybrids exhibited an error frequency
      similar to that of rdn5 alone, despite the error-prone mutation in S23. This was
      accompanied by extreme resistance to paromomycin, unlike the effects of the
      individual mutations. Furthermore, rdn5 lowers peptidyltransferase activity
      measured as a second-order rate constant (kcat/K(s)) corresponding to the rate of
      peptide bond formation. This mutation was also found to affect translocation.
      Elongation factor 2 (EF2)-dependent translocation of Ac-Phe-tRNA from the A- to P
      site was achieved at an EF2 concentration 3.5 times lower than in wild type. In
      conclusion, the sarcin/ricin domain of 25S rRNA influences decoding, peptide bond
      formation and translocation.

PMID- 15477391
TI  - Microfluidic PicoArray synthesis of oligodeoxynucleotides and simultaneous
      assembling of multiple DNA sequences.
AB  - Large DNA constructs of arbitrary sequences can currently be assembled with
      relative ease by joining short synthetic oligodeoxynucleotides
      (oligonucleotides). The ability to mass produce these synthetic genes readily
      will have a significant impact on research in biology and medicine. Presently,
      high-throughput gene synthesis is unlikely, due to the limits of oligonucleotide
      synthesis. We describe a microfluidic PicoArray method for the simultaneous
      synthesis and purification of oligonucleotides that are designed for multiplex
      gene synthesis. Given the demand for highly pure oligonucleotides in gene
      synthesis processes, we used a model to improve key reaction steps in DNA
      synthesis. The oligonucleotides obtained were successfully used in ligation under
      thermal cycling conditions to generate DNA constructs of several hundreds of base
      pairs. Protein expression using the gene thus synthesized was demonstrated. We
      used a DNA assembly strategy, i.e. ligation followed by fusion PCR, and achieved
      effective assembling of up to 10 kb DNA constructs. These results illustrate the
      potential of microfluidics-based ultra-fast oligonucleotide parallel synthesis as
      an enabling tool for modern synthetic biology applications, such as the
      construction of genome-scale molecular clones and cell-free large scale protein
      expression.

PMID- 15477392
TI  - Cross talk between the +73/294 interaction and the cleavage site in RNase P RNA
      mediated cleavage.
AB  - To monitor functionally important metal ions and possible cross talk in RNase P
      RNA mediated cleavage we studied cleavage of substrates, where the 2'OH at the
      RNase P cleavage site (at -1) and/or at position +73 had been replaced with a 2'
      amino group (or 2'H). Our data showed that the presence of 2' modifications at
      these positions affected cleavage site recognition, ground state binding of
      substrate and/or rate of cleavage. Cleavage of 2' amino substituted substrates at
      different pH showed that substitution of Mg2+ by Mn2+ (or Ca2+), identity of
      residues at and near the cleavage site, and addition of C5 protein influenced the
      frequency of miscleavage at -1 (cleavage at the correct site is referred to as
      +1). From this we infer that these findings point at effects mediated by
      protonation/deprotonation of the 2' amino group, i.e. an altered charge
      distribution, at the site of cleavage. Moreover, our data suggested that the
      structural architecture of the interaction between the 3' end of the substrate
      and RNase P RNA influence the charge distribution at the cleavage site as well as
      the rate of cleavage under conditions where the chemistry is suggested to be rate
      limiting. Thus, these data provide evidence for cross talk between the +73/294
      interaction and the cleavage site in RNase P RNA mediated cleavage. We discuss
      the role metal ions might play in this cross talk and the likelihood that at
      least one functionally important metal ion is positioned in the vicinity of, and
      use the 2'OH at the cleavage site as an inner or outer sphere ligand.

PMID- 15477393
TI  - Mitochondrial tRNA 3' end metabolism and human disease.
AB  - Over 150 mutations in the mitochondrial genome have been shown to be associated
      with human disease. Remarkably, two-thirds of them are found in tRNA genes, which
      constitute only one-tenth of the mitochondrial genome. A total of 22 tRNAs
      punctuate the genome and are produced together with 11 mRNAs and 2 rRNAs from
      long polycistronic primary transcripts with almost no spacers. Pre-tRNAs thus
      require precise endonucleolytic excision. Furthermore, the CCA triplet which
      forms the 3' end of all tRNAs is not encoded, but must be synthesized by the CCA
      adding enzyme after 3' end cleavage. Amino acid attachment to the CCA of mature
      tRNA is performed by aminoacyl-tRNA synthetases, which, like the preceding
      processing enzymes, are nuclear-encoded and imported into mitochondria. Here, we
      critically review the effectiveness and reliability of evidence obtained from
      reactions with in vitro transcripts that pathogenesis-associated mutant
      mitochondrial tRNAs can lead to deficiencies in tRNA 3' end metabolism (3' end
      cleavage, CCA addition and aminoacylation) toward an understanding of molecular
      mechanisms underlying human tRNA disorders. These defects probably contribute,
      individually and cumulatively, to the progression of human mitochondrial
      diseases.

PMID- 15477394
TI  - Interaction of mitochondrial initiation factor 2 with mitochondrial fMet-tRNA.
AB  - The mammalian mitochondrial genome contains a single tRNA(Met) gene that gives
      rise to the initiator and elongator tRNA(Met). It is generally believed that
      mitochondrial protein synthesis begins with formylmethionyl-tRNA, which indicates
      that the formylation of mitochondrial Met-tRNA specifies its participation in
      initiation through its interaction with initiation factor 2 (IF-2). However,
      recent studies in yeast mitochondria, suggest that formylation is not required
      for protein synthesis. In addition, bovine IF-2(mt) could replace yeast IF-2(mt)
      in strains that lack fMet-tRNA which suggests that this paradigm may extend to
      mammalian mitochondria. Here, the importance of the formylation of mitochondrial
      Met-tRNA for the interaction with IF-2(mt) was investigated by measuring the
      ability of bovine IF-2(mt) to bind mitochondrial fMet-tRNA. In direct binding
      experiments, bovine IF-2(mt) has a 25-fold greater affinity for mitochondrial
      fMet-tRNA than Met-tRNA, using either the native mitochondrial tRNA(Met) or an in
      vitro transcript of bovine mitochondrial tRNA(Met). In addition, IF-2(mt) will
      not effectively stimulate mitochondrial Met-tRNA binding to mitochondrial
      ribosomes, exhibiting a 50-fold preference for fMet-tRNA over Met-tRNA in this
      assay. Finally, the region of IF-2(mt) responsible for the interaction with fMet
      tRNA was mapped to the C2 sub-domain of domain VI of this factor.

PMID- 15477395
TI  - A comprehensive comparison of DNA replication past 2-deoxyribose and its
      tetrahydrofuran analog in Escherichia coli.
AB  - Apurinic/apyrimidinic (AP) sites are alkali labile lesions that, when encountered
      during DNA replication, can block polymerases or potentially result in mutagenic
      events. Owing to the instability of 2-deoxyribose lesions (AP), a chemically
      stable tetrahydrofuran analog (F) is often used as a model of abasic sites. A
      comparison of the two lesions in Saccharomyces cerevisiae revealed that the model
      lesion and 2-deoxyribose have distinct in vivo effects. Comprehensive comparative
      analyses of F and AP have not been carried out in Escherichia coli. We conducted
      a side-by-side investigation of F and AP in E.coli to compare their biological
      effects and interactions with SOS polymerases. Both lesions were examined in SOS
      induced and uninduced cells. Our studies reveal that in uninduced E.coli the
      effects of individual polymerases in the replication of plasmids containing F or
      AP are distinct. However, when cells are SOS-induced, the biological effects of F
      and AP are similar.

PMID- 15477396
TI  - Selecting patients with atrial fibrillation for anticoagulation: stroke risk
      stratification in patients taking aspirin.
AB  - BACKGROUND: The rate of stroke in atrial fibrillation (AF) depends on the
      presence of comorbid conditions and the use of antithrombotic therapy. Although
      adjusted-dose warfarin is superior to aspirin for reducing stroke in AF, the
      absolute risk reduction of warfarin depends on the stroke rate with aspirin. This
      prospective cohort study tested the predictive accuracy of 5 stroke risk
      stratification schemes. METHODS AND RESULTS: The study pooled individual data
      from 2580 participants with nonvalvular AF who were prescribed aspirin in a
      multicenter trial (Atrial Fibrillation, Aspirin, Anticoagulation I study [AFASAK
      1], AFASAK-2, European Atrial Fibrillation Trial, Primary Prevention of Arterial
      Thromboembolism in patients with nonrheumatic Atrial Fibrillation in primary care
      study, and Stroke Prevention and Atrial Fibrillation [SPAF]-III high risk or SPAF
      III low risk). There were 207 ischemic strokes during 4887 patient-years of
      aspirin therapy. All schemes predicted stroke better than chance, but the number
      of patients categorized as low and high risk varied substantially. AF patients
      with prior cerebral ischemia were classified as high risk by all 5 schemes and
      had 10.8 strokes per 100 patient-years. The CHADS(2) scheme (an acronym for
      Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior
      Stroke or transient ischemic attack) successfully identified primary prevention
      patients who were at high risk of stroke (5.3 strokes per 100 patient-years). In
      contrast, patients identified as high risk by other schemes had 3.0 to 4.2
      strokes per 100 patient-years. Low-risk patients identified by all schemes had
      0.5 to 1.4 strokes per 100 patient-years of therapy. CONCLUSIONS: Patients with
      AF who have high and low rates of stroke when given aspirin can be reliably
      identified, allowing selection of antithrombotic prophylaxis to be
      individualized.

PMID- 15477397
TI  - Impact of prior use or recent withdrawal of oral antiplatelet agents on acute
      coronary syndromes.
AB  - BACKGROUND: Oral antiplatelet agents (OAAs) can prevent further vascular events
      in cardiovascular disease. How prior use or recent discontinuation of OAA affects
      clinical presentation of acute coronary syndromes (ACS) and clinical outcomes
      (death, myocardial infarction [MI]) is unclear. METHODS AND RESULTS: We studied
      and followed up for up to 30 days a cohort of 1358 consecutive patients admitted
      for a suspected ACS; of these, 930 were nonusers, 355 were prior users of OAA,
      and 73 had recently withdrawn OAA. Nonusers were at lower risk, more frequently
      presented with ST-elevation MI on admission, and more frequently had Q-wave MI at
      discharge than prior users (36.6% versus 17.5%, P<0.001; and 47.8% versus 28.2%,
      P<0.001, respectively). However, there was no difference regarding the incidence
      of death or MI at 30 days between nonusers and prior users (10.3% versus 12.4%,
      P=NS). In addition, prior users experienced more major bleeds within 30 days
      compared with nonusers (3.4% versus 1.4%, respectively; P=0.04). Recent
      withdrawers were admitted on average 11.9+/-0.8 days after OAA withdrawal.
      Interruption was primarily a physician decision for scheduled surgery (n=47 of
      73). Despite a similar cardiovascular risk profile, recent withdrawers had higher
      30-day rates of death or MI (21.9% versus 12.4%, P=0.04) and bleedings (13.7%
      versus 5.9%, P=0.03) than prior users. After multivariate analysis, OAA
      withdrawal was found to be an independent predictor of both mortality and
      bleedings at 30 days. CONCLUSIONS: Among ACS patients, prior users represent a
      higher-risk population and present more frequently with non-ST-elevation ACS than
      nonusers. Although patients with a recent interruption of OAA resemble those
      chronically treated by OAA, they display worse clinical outcomes.

PMID- 15477398
TI  - Statin-induced cholesterol lowering and plaque regression after 6 months of
      magnetic resonance imaging-monitored therapy.
AB  - BACKGROUND: Statin therapy reduces adverse outcomes, with a minimal decrease in
      vessel stenosis. Magnetic resonance imaging (MRI) noninvasively detects
      atherosclerotic plaque (AP) reduction. We hypothesized that statin-induced AP
      regression can be monitored by MRI and detected earlier than previously reported
      and is significantly associated with its lipid-lowering effect. METHODS AND
      RESULTS: APs in thoracic aorta were measured by combined surface/transesophageal
      MRI in 27 patients (treated with simvastatin 20 to 80 mg daily) before and after
      6 months of therapy. AP volume and luminal dimensions were measured from 6 cross
      sections used to construct a 2.4-cm 3D volume of the aorta that included plaque
      and lumen. Method reproducibility was studied in 10 patients imaged twice, 1 week
      apart. AP volume was reduced from 3.3+/-0.1.4 to 2.9+/-1.4 cm3 at 6 months
      (P<0.02), whereas luminal volume increase was less accentuated (from 12.0+/-3.9
      to 12.2+/-3.7 cm3, P<0.06). LDL cholesterol decreased by 23% (from 125+/-32 to
      97+/-27 mg/dL, P<0.05) in 6 months. AP regression (plaque volume/area reduction)
      was significantly related to LDL cholesterol reduction (P<0.02 and P<0.005,
      respectively), and luminal volume increase was inversely related to LDL
      cholesterol reduction (P<0.04). Plaque volume measurement was highly reproducible
      (intraclass correlation R=0.98 and variability=4.8%). Intraobserver (0.91) and
      interobserver (0.81) concordances were documented for plaque volume assessment.
      CONCLUSIONS: AP regression and reverse remodeling can be detected accurately by
      MRI 6 months after statin therapy initiation, and it is strongly associated with
      LDL cholesterol reduction.

PMID- 15477399
TI  - Cystatin C: a novel predictor of outcome in suspected or confirmed non-ST
      elevation acute coronary syndrome.
AB  - BACKGROUND: Patients with suspected or confirmed non-ST-elevation acute coronary
      syndrome (ACS) constitute a large and heterogeneous group. Measurements of renal
      function such as serum creatinine and estimation of creatinine clearance carry
      independent prognostic information in this population. Cystatin C is a new and
      better marker of renal function than creatinine. The aim was therefore to
      evaluate the prognostic value of cystatin C in this population. METHODS AND
      RESULTS: Cystatin C was analyzed on admission in 726 patients admitted because of
      symptoms suggestive of an acute coronary syndrome and no ST-segment elevations.
      Patients were followed up with regard to death and myocardial infarction for a
      median of 40 and 6 months, respectively. The median cystatin C level was 1.00
      mg/L (25th to 75th percentile, 0.83 to 1.24 mg/L). The risk of death during
      follow-up increased with increasing levels of cystatin C. In the group with non
      ST-elevation ACS, patients in the second, third, and fourth quartiles had a
      relative risk of subsequent death of 1.8 (95% CI, 0.6 to 5.3), 3.2 (95% CI, 1.2
      to 8.5), and 11.7 (95% CI, 4.7 to 29.3) compared with the lowest quartile. In Cox
      regression models including well-known predictors of outcome, cystatin C level
      was independently associated with mortality but not with the risk of subsequent
      myocardial infarction. In a comparison of the markers of renal function in
      receiver-operating curve analyses, cystatin C had the best ability to
      discriminate between survivors and nonsurvivors. CONCLUSIONS: A single
      measurement of cystatin C will substantially improve the early risk
      stratification of patients with suspected or confirmed non-ST-elevation ACS.

PMID- 15477400
TI  - Associations of parental, birth, and early life characteristics with systolic
      blood pressure at 5 years of age: findings from the Mater-University study of
      pregnancy and its outcomes.
AB  - BACKGROUND: We examined the associations of a range of parental and early life
      characteristics with systolic blood pressure at 5 years of age. METHODS AND
      RESULTS: Information from 3864 children who were followed up prospectively from
      their mother's first antenatal clinic assessment was used. Maternal age, body
      mass index, and smoking during pregnancy were all positively associated with
      offspring systolic blood pressure at 5 years of age. The systolic blood pressure
      of children whose mothers had smoked throughout pregnancy was on average 0.92 mm
      Hg (95% CI 0.17 to 1.68) greater than that of children whose mothers had never
      smoked, after full adjustment. Children who had been breast fed until at least 6
      months had lower systolic blood pressure than those who were breast fed for a
      shorter duration. Paternal body mass index and child's weight, height, and body
      mass index were all positively associated with blood pressure at age 5.
      CONCLUSIONS: Because childhood blood pressure tracks into adulthood,
      interventions aimed at early life risk factors, such as quitting smoking during
      pregnancy, breast feeding, and prevention of obesity in all family members, may
      be important for reducing the population distribution of blood pressure and thus
      cardiovascular disease risk.

PMID- 15477401
TI  - Effect of simvastatin and antioxidant vitamins on atrial fibrillation promotion
      by atrial-tachycardia remodeling in dogs.
AB  - BACKGROUND: There is evidence for a role of oxidant stress and inflammation in
      atrial fibrillation (AF). Statins have both antioxidant and antiinflammatory
      properties. We compared the effects of simvastatin with those of antioxidant
      vitamins on AF promotion by atrial tachycardia in dogs. METHODS AND RESULTS: We
      studied dogs subjected to atrial tachypacing (ATP) at 400 bpm in the absence and
      presence of treatment with simvastatin, vitamin C, and combined vitamins C and E.
      Serial closed-chest electrophysiological studies were performed in each dog at
      baseline and 2, 4, and 7 days after tachypacing onset. Atrioventricular block was
      performed to control ventricular rate. Mean duration of induced AF was increased
      from 42+/-18 to 1079+/-341 seconds at terminal open-chest study after tachypacing
      alone (P<0.01), and atrial effective refractory period (ERP) at a cycle length of
      300 ms was decreased from 117+/-5 to 76+/-6 ms (P<0.01). Tachypacing-induced ERP
      shortening and AF promotion were unaffected by vitamin C or vitamins C and E;
      however, simvastatin suppressed tachypacing-induced remodeling effects
      significantly, with AF duration and ERP averaging 41+/-15 seconds and 103+/-4 ms,
      respectively, after tachypacing with simvastatin therapy. Tachypacing
      downregulated L-type Ca2+-channel alpha-subunit expression (Western blot), an
      effect that was unaltered by antioxidant vitamins but greatly attenuated by
      simvastatin. CONCLUSIONS: Simvastatin attenuates AF promotion by atrial
      tachycardia in dogs, an effect not shared by antioxidant vitamins, and
      constitutes a potentially interesting new pharmacological approach to preventing
      the consequences of atrial tachycardia remodeling.

PMID- 15477402
TI  - Increased short-term variability of repolarization predicts d-sotalol-induced
      torsades de pointes in dogs.
AB  - BACKGROUND: Identification of patients at risk for drug-induced torsades de
      pointes arrhythmia (TdP) is difficult. Increased temporal lability of
      repolarization has been suggested as being valuable to predict proarrhythmia. The
      predictive value of different repolarization parameters, including beat-to-beat
      variability of repolarization (BVR), was compared in this serial investigation in
      dogs with chronic AV block. METHODS AND RESULTS: In anesthetized dogs with
      electrically remodeled hearts, the dose-dependent difference in drug-induced TdP
      (d-sotalol, 2 and 4 mg/kg IV over 5 minutes, 25% and 75% TdP, respectively) could
      not be accounted for by prolongation of QT(c) (410+/-37 to 475+/-60 versus 415+/
      47 to 484+/-52 ms, respectively). BVR was quantified by Poincare plots at
      baseline and immediately before onset of d-sotalol-induced extrasystolic
      activity. TdP occurrence was associated with an increase in short-term
      variability (STV) of the left ventricular monophasic action potential duration
      (3.5+/-1.5 to 5.5+/-1.6 versus 3.0+/-0.7 to 8.6+/-3.8 ms, respectively), which
      was reversible when TdP was abolished by I(K,ATP) activation. The absence of TdP
      despite QT(c) prolongation after chronic amiodarone treatment could also be
      explained by an unchanged STV. In experiments with isolated ventricular myocytes,
      STV increased after I(Kr) block and was highest in cells that subsequently showed
      early afterdepolarizations. CONCLUSIONS: Proarrhythmia is not related to
      differences in prolongation of repolarization but corresponds to BVR, here
      quantified as STV of the left ventricle. STV could be a new parameter to predict
      drug-induced TdP in patients.

PMID- 15477403
TI  - Ongoing myocardial injury in stable severe heart failure: value of cardiac
      troponin T monitoring for high-risk patient identification.
AB  - BACKGROUND: The progression of chronic heart failure (CHF) is related to ongoing
      myocyte loss, which can be detected by cardiac troponin T (cTnT). We examined the
      prevalence and prognostic value of increased cTnT concentrations in serial blood
      specimens from patients with severe CHF. METHODS AND RESULTS: Clinical,
      echocardiographic, and 6-minute walk test data were collected prospectively at
      baseline and at 1 year in 115 outpatients (mean age, 61+/-11 years; 75% men; 62%
      coronary heart disease) with CHF and a left ventricular ejection fraction <40%.
      Blood samples were collected at baseline and at 3, 6, and 12 months of follow-up.
      cTnT concentrations > or =0.02 ng/mL were considered abnormal, and a Tn index
      (highest cTnT measurement/0.02 ng/mL) was calculated. In 62 patients (54%), cTnT
      was consistently <0.02 ng/mL (group 1); 28 (24%) had a single abnormal cTnT
      result (group 2); and 25 (22%) had > or =2 abnormal cTnT results (group 3). At 18
      months, CHF hospitalization-free survival was 63%, 46%, and 17%, respectively
      (P=0.0001). In a Cox proportional-hazards model, hospitalization for worsening
      CHF in the previous year (HR=2.1; 95% CI, 1.1 to 4.1), functional class III-IV
      (HR=2.3; 95% CI, 1.1 to 4.6), and number of abnormal cTnT samples (HR=1.6; 95%
      CI, 1.1 to 2.4) were independently associated with prognosis. A cTnT rise of
      0.020 ng/mL in any sample was associated with an excess of 9% (95% CI, 1% to 18%)
      in the incidence of combined end point. CONCLUSIONS: Abnormal cTnT concentrations
      were detected in >50% of outpatients with advanced CHF. This ongoing myocardial
      necrosis was a strong predictor of worsening CHF, suggesting a role of cTnT-based
      monitoring to identify high-risk patients.

PMID- 15477404
TI  - Maturation of cardiovagal autonomic function from childhood to young adult age.
AB  - BACKGROUND: Cardiovagal autonomic control declines with age in adult subjects,
      which is related in part to increasing stiffness of the barosensory vessel wall.
      It is not known, however, whether autonomic function changes with age in
      children. METHODS AND RESULTS: We studied 137 healthy subjects divided into 4 age
      groups: group 1, 7 to 14 years; group 2, 11 to 14 years; group 3, 15 to 18 years;
      and group 4, 19 to 22 years. Brachial artery pressure was measured by
      sphygmomanometry and continuous radial artery pressure and carotid artery pulse
      pressure (DeltaP) by applanation tonometry. The R-R interval was derived from the
      ECG. Autonomic function was assessed by spontaneous sequence and frequency-domain
      indices, which indicate the extent of coupling between fluctuations in heart rate
      and systolic pressure. Carotid artery diastolic diameter (DD) and pulsatile
      distension (DeltaD) were measured by echo wall tracking; carotid compliance
      coefficient (CC) was defined as DeltaD/DeltaP and distensibility coefficient as
      2DeltaD/DD . DeltaP. From group 1 to group 3, spontaneous indices increased
      significantly (18.1+/-1.7 versus 33.3+/-4.0; 14.4+/-1.1 versus 25.5+/-22; 12.9+/
      1.1 versus 20.8+/-2.0; and 6.4+/-0.6 versus 16.2+/-1.4 ms/mm Hg [mean+/-SEM] for
      Seq+, Seq-, LFalpha, and LF(gain), respectively), with no significant changes
      afterward. CC and DC were inversely proportional to age (r=-0.49 and -0.62,
      respectively, P<0.001). The efficiency of neural integrative mechanisms,
      estimated as the ratio of spontaneous indices and CC, more than doubled from
      group 1 to group 3. Spontaneous indices were linearly related to measures of
      cardiac vagal activity. CONCLUSIONS: The increase in spontaneous indices from
      early childhood to adolescence, despite gradual stiffening of the carotid artery,
      may indicate improved cardiovagal autonomic function, which is most likely a
      result of maturation of neural mechanisms, attaining peak level at adolescence.

PMID- 15477405
TI  - Role of IKur in controlling action potential shape and contractility in the human
      atrium: influence of chronic atrial fibrillation.
AB  - BACKGROUND: The ultrarapid outward current I(Kur) is a major repolarizing current
      in human atrium and a potential target for treating atrial arrhythmias. The
      effects of selective block of I(Kur) by low concentrations of 4-aminopyridine or
      the biphenyl derivative AVE 0118 were investigated on right atrial action
      potentials (APs) in trabeculae from patients in sinus rhythm (SR) or chronic
      atrial fibrillation (AF). METHODS AND RESULTS: AP duration at 90% repolarization
      (APD90) was shorter in AF than in SR (300+/-16 ms, n=6, versus 414+/-10 ms,
      n=15), whereas APD20 was longer (35+/-9 ms in AF versus 5+/-2 ms in SR, P<0.05).
      4-Aminopyridine (5 micromol/L) elevated the plateau to more positive potentials
      from -21+/-3 to -6+/-3 mV in SR and 0+/-3 to +12+/-3 mV in AF. 4-Aminopyridine
      reversibly shortened APD90 from 414+/-10 to 350+/-10 ms in SR but prolonged APD90
      from 300+/-16 to 320+/-13 ms in AF. Similar results were obtained with AVE 0118
      (6 micromol/L). Computer simulations of I(Kur) block in human atrial APs
      predicted secondary increases in I(Ca,L) and in the outward rectifiers I(Kr) and
      I(Ks), with smaller changes in AF than SR. The indirect increase in I(Ca,L) was
      supported by a positive inotropic effect of 4-aminopyridine without direct
      effects on I(Ca,L) in atrial but not ventricular preparations. In accordance with
      the model predictions, block of I(Kr) with E-4031 converted APD shortening
      effects of I(Kur) block in SR into AP prolongation. CONCLUSIONS: Whether
      inhibition of I(Kur) prolongs or shortens APD depends on the disease status of
      the atria and is determined by the level of electrical remodeling.

PMID- 15477406
TI  - Electroanatomic substrate and outcome of catheter ablative therapy for
      ventricular tachycardia in setting of right ventricular cardiomyopathy.
AB  - BACKGROUND: To gain insight into the pathogenesis of right ventricular (RV)
      cardiomyopathy and ventricular tachycardia (VT), we determined the clinical and
      electroanatomic characteristics and outcome of ablative therapy in consecutive
      patients with (1) RV dilatation, (2) multiple left bundle-branch block (LBBB)
      type VTs, and (3) an abnormal endocardial substrate defined by contiguous
      electrogram abnormalities. METHODS AND RESULTS: All 21 patients had detailed RV
      bipolar electrogram voltage mapping. Eighteen patients had simultaneous left
      ventricular (LV) mapping, including all 4 patients with right bundle-branch block
      (RBBB) VT. VT was ablated in 19 patients by use of focal and/or linear lesions
      with irrigated-tip catheters in 10 of 19 patients. Eighteen patients were men,
      age 47+/-18 years, and none had a family history of RV dysplasia. RV volume was
      223+/-89 cm3. Electrogram abnormalities extended from perivalvular tricuspid
      valves (5 patients), pulmonic valves (6 patients), or both valves (10 patients).
      Electrogram abnormalities always involved free wall, spared the apex, and
      included the septum in 15 patients (71%). The area of abnormality was 55+/-37 cm2
      (range, 12 to 130 cm2) and represented 34+/-19% of the RV. In 52 of 66 LBBB VTs,
      the origin was from the RV perivalvular region. LV perivalvular low-voltage areas
      noted in 5 patients were associated with a RBBB VT origin. No VT recurred after
      ablation in 17 patients (89%) during 27+/-22 months. CONCLUSIONS: In patients
      with RV cardiomyopathy and VT, (1) perivalvular electrogram abnormalities
      represent the commonly identified substrate and source of most VT, (2) LV
      perivalvular endocardial electrogram abnormalities and VT can occasionally be
      identified, and (3) aggressive ablative therapy provides long-term VT control.

PMID- 15477407
TI  - Engineered zinc finger-activating vascular endothelial growth factor
      transcription factor plasmid DNA induces therapeutic angiogenesis in rabbits with
      hindlimb ischemia.
AB  - BACKGROUND: Therapeutic angiogenesis seeks to promote blood vessel growth to
      improve tissue perfusion. Vascular endothelial growth factor (VEGF) exists in
      multiple isoforms. We investigated an engineered zinc finger-containing
      transcription factor plasmid designed to activate the endogenous VEGF gene (ZFP
      VEGF). METHODS AND RESULTS: New Zealand White rabbits (n=56) underwent unilateral
      femoral artery ligation and excision. At day 10 postoperatively, the ischemic
      muscle received ZFP treatment (500 microg ZFP-VEGF plasmid) or no ZFP treatment
      (beta-galactosidase, empty, or no plasmid). Group 1 (n=13) was harvested 3 days
      after injection to examine VEGF mRNA by real-time polymerase chain reaction and
      protein by ELISA. Groups 2 (n=13) and 3 (n=10) were harvested 11 days after
      injection. Group 2 was studied by histology and group 3, by histology and changes
      in blood flow. Groups 4 and 5 (n=10 each) were harvested 22 and 32 days after
      injection, respectively, and studied for changes in blood flow. In group 1, VEGF
      mRNA copy numbers were significantly higher for VEGF121, VEGF165, VEGF189, and
      protein in the ZFP-VEGF-treatment versus no-ZFP-treatment arms. In groups 2 and
      3, capillary density and proliferating cells were significantly greater and
      apoptosis significantly lower in the treatment versus no-treatment arms. Changes
      in the blood flow ratio of the ischemic to the nonischemic limb were
      significantly greater in the treatment versus no-ZFP-treatment groups (6.57+/
      1.52% versus 3.38+/-0.87%, P<0.005; 13.15+/-1.77% versus 6.13+/-1.55%, P<0.001;
      and 20.16+/-2.84% versus 13.88+/-3.14%, P<0.01, for groups 3, 4, and 5,
      respectively). CONCLUSIONS: This engineered ZFP-VEGF-activating transcription
      factor may provide a novel approach to treat peripheral arterial disease.

PMID- 15477408
TI  - Angiogenesis-dependent and independent phases of intimal hyperplasia.
AB  - BACKGROUND: Neointimal vascular smooth muscle cell (VSMC) proliferation is a
      primary cause of occlusive vascular disease, including atherosclerosis,
      restenosis after percutaneous interventions, and bypass graft stenosis.
      Angiogenesis is implicated in the progression of early atheromatous lesions in
      animal models, but its role in neointimal VSMC proliferation is undefined.
      Because percutaneous coronary interventions result in induction of
      periadventitial angiogenesis, we analyzed the role of this process in neointima
      formation. METHODS AND RESULTS: Local injury to the arterial wall in 2 different
      animal models induced periadventitial angiogenesis and neointima formation.
      Application of angiogenesis stimulators vascular endothelial growth factor (VEGF
      A165) or a proline/arginine-rich peptide (PR39) to the adventitia of the injured
      artery induced a marked increase in neointimal thickening beyond that seen with
      injury alone in both in vivo models. Inhibition of either VEGF (with soluble VEGF
      receptor 1 [sFlt1]) or fibroblast growth factor (FGF) (with a dominant=negative
      form of FGF receptor 1 [FGF-R1DN]), respectively, signaling reduced adventitial
      thickening induced by VEGF and PR39 to the level seen with mechanical arterial
      injury alone. However, neither inhibitor was effective in preventing neointimal
      thickening after mechanical injury when administered in the absence of angiogenic
      growth factor. CONCLUSIONS: Our findings indicate that adventitial angiogenesis
      stimulates intimal thickening but does not initiate it.

PMID- 15477409
TI  - Blockade of vascular endothelial growth factor suppresses experimental restenosis
      after intraluminal injury by inhibiting recruitment of monocyte lineage cells.
AB  - BACKGROUND: Therapeutic angiogenesis by delivery of vascular endothelial growth
      factor (VEGF) has attracted attention. However, the role and function of VEGF in
      experimental restenosis (neointimal formation) after vascular intraluminal injury
      have not been addressed. METHODS AND RESULTS: We report herein that blockade of
      VEGF by soluble VEGF receptor 1 (sFlt-1) gene transfer attenuated neointimal
      formation after intraluminal injury in rabbits, rats, and mice. sFlt-1 gene
      transfer markedly attenuated the early vascular inflammation and proliferation
      and later neointimal formation. sFlt-1 gene transfer also inhibited increased
      expression of inflammatory factors such as monocyte chemoattractant protein-1 and
      VEGF. Intravascular VEGF gene transfer enhanced angiogenesis in the adventitia
      but did not reduce neointimal formation. CONCLUSIONS: Increased expression and
      activity of VEGF are essential in the development of experimental restenosis
      after intraluminal injury by recruiting monocyte-lineage cells.

PMID- 15477410
TI  - Atrial fibrillation after surgical correction of mitral regurgitation in sinus
      rhythm: incidence, outcome, and determinants.
AB  - BACKGROUND: The incidence, determinants, and outcome of postoperative atrial
      fibrillation (AF) after surgery for mitral regurgitation (MR) are poorly defined
      but may have important implications for timing of mitral valve surgery. METHODS
      AND RESULTS: In 762 patients in sinus rhythm with no AF history undergoing MR
      surgical correction, we examined the rates and prognostic implications of
      postoperative AF for early AF (within 2 weeks postoperatively) and late AF (>2
      weeks after surgery). During postoperative follow-up, 180 patients (24%)
      experienced new AF (early AF in 136 and late AF in 111). Isolated early AF
      without recurrence was observed in 69 patients characterized by high angina class
      and lower left ventricular ejection fraction but no significant left atrial (LA)
      enlargement. However, overall early AF predicted late AF: 62+/-5% of patients
      with early AF had late AF at 10 years compared with 9+/-1% of patients without
      early AF (P<0.0001). Large LA size strongly and independently predicted early AF
      (P=0.01) and late AF (P=0.003). For late AF, the predictive value of an enlarged
      LA was cumulative to that of early AF. Postoperative AF was associated with an
      increased subsequently higher risk of stroke or congestive heart failure
      (adjusted risk ratio=1.46 [1.04 to 2.05], P=0.03). CONCLUSIONS: Postoperative AF
      is common after surgical correction of MR in patients with no prior history of AF
      and is associated with increased subsequent morbidity. LA enlargement is
      independently predictive of postoperative AF and as such, should be integrated
      into the clinical decision-making process in patients with MR.

PMID- 15477411
TI  - There is no evidence for an increase in acute coronary syndromes after short-term
      abrupt discontinuation of statins in stable cardiac patients.
AB  - BACKGROUND: For a variety of reasons, many patients abruptly discontinue statin
      therapy. The present analysis was conducted to determine whether the risk of
      cardiovascular outcomes increases after withdrawal of statin therapy in a stable
      cardiac population. METHODS AND RESULTS: In the Treating to New Target (TNT)
      study, 2 doses of atorvastatin (10 and 80 mg once daily) are being used in a
      double-blind parallel-group design. Of the 18,468 patients screened for study
      participation, 16,619 entered a dietary lead-in/drug-washout period, and of
      these, 15,432 eligible participants began treatment with atorvastatin 10 mg/d on
      an open-label basis. Of the subjects who entered the dietary lead-in/drug-washout
      period, 57% were receiving prior statin therapy. During the 6-week drug-washout
      period, there were 24 primary events (defined as coronary heart disease death,
      nonfatal myocardial infarction, resuscitated cardiac arrest, and fatal or
      nonfatal stroke); throughout the subsequent 8-week open-label period, there were
      31 primary events. This equated to monthly Kaplan-Meier event rates of 0.20%
      during washout and 0.26% in the open-label phase. Event rates were therefore
      similar during the 2 phases. CONCLUSIONS: The present analysis demonstrates that
      short-term discontinuation of statin therapy in stable cardiac patients
      apparently does not lead to a clinically important increased risk of acute
      coronary syndromes.

PMID- 15477412
TI  - Prevalence of the metabolic syndrome in American adolescents: findings from the
      Third National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Metabolic syndrome (MetS) is defined by the Third Report of the Adult
      Treatment Panel (ATP III) using criteria easily applied by clinicians and
      researchers. There is no standard pediatric definition. METHODS AND RESULTS: We
      defined pediatric MetS using criteria analogous to ATP III as > or =3 of the
      following: (1) fasting triglycerides > or =1.1 mmol/L (100 mg/dL); (2) HDL <1.3
      mmol/L (50 mg/dL), except in boys aged 15 to 19 years, in whom the cutpoint was
      <1.2 mmol/L (45 mg/dL); (3) fasting glucose > or =6.1 mmol/L (110 mg/dL); (4)
      waist circumference >75th percentile for age and gender; and (5) systolic blood
      pressure >90th percentile for gender, age, and height. MetS prevalence in US
      adolescents was estimated with the Third National Health and Nutritional Survey
      1988 to 1994. Among 1960 children aged > or =12 years who fasted > or =8 hours,
      two thirds had at least 1 metabolic abnormality, and nearly 1 in 10 had MetS. The
      racial/ethnic distribution was similar to adults: Mexican-Americans, followed by
      non-Hispanic whites, had a greater prevalence of MetS compared with non-Hispanic
      blacks (12.9%, [95% CI 10.4% to 15.4%]; 10.9%, [95% CI 8.4% to 13.4%]; and 2.5%,
      [95% CI 1.3% to 3.7%], respectively). Nearly one third (31.2% [95% CI 28.3% to
      34.1%]) of overweight/obese adolescents had MetS. CONCLUSIONS: Our definition of
      pediatric MetS, designed to be closely analogous to ATP III, found MetS is common
      in adolescents and has a similar racial/ethnic distribution to adults in this
      representative national sample. Because childhood MetS likely tracks into
      adulthood, early identification may help target interventions to improve future
      cardiovascular health.

PMID- 15477413
TI  - Opposite patterns of left ventricular remodeling after coronary revascularization
      in patients with ischemic cardiomyopathy: role of myocardial viability.
AB  - BACKGROUND: In patients with ischemic cardiomyopathy, left ventricular (LV)
      remodeling is an important prognostic indicator. The precise relation between
      viable myocardium, revascularization, and ongoing or reversed remodeling is
      unknown and was evaluated in the present study. METHODS AND RESULTS: A total of
      100 patients with ischemic cardiomyopathy underwent dobutamine stress
      echocardiography to assess myocardial viability and LV geometry (volumes and
      shape). At a mean of 10.2 months and 4.5 years after revascularization, resting
      echocardiography was repeated to evaluate LV remodeling. Long-term follow-up
      (mean 5+/-2 years) data were obtained. According to dobutamine stress
      echocardiography, 44 patients (44%) were defined as viable (> or =4 viable
      segments) and 56 as nonviable. After revascularization, 40 patients (43%) had
      ongoing LV remodeling and 53 (57%) did not (in 7 patients who died early after
      revascularization, postoperative echocardiographic evaluation was not available).
      On multivariable analysis, the number of viable segments was the only predictor
      of ongoing LV remodeling (OR 0.60, 95% CI 0.48 to 0.75; P<0.0001). The likelihood
      of LV remodeling decreased as the number of viable segments increased. During the
      follow-up, reverse remodeling was present in viable patients, whereas in
      nonviable patients, LV volumes significantly increased, which indicates ongoing
      LV remodeling. At follow-up, viable patients also showed a persistent improvement
      of heart failure symptoms and fewer cardiac events than nonviable patients
      (P<0.05). CONCLUSIONS: In patients with ischemic cardiomyopathy, a substantial
      amount of viable myocardium prevents ongoing LV remodeling after
      revascularization and is associated with persistent improvement of symptoms and
      better outcome.

PMID- 15477414
TI  - Broad-spectrum CC-chemokine blockade by gene transfer inhibits macrophage
      recruitment and atherosclerotic plaque formation in apolipoprotein E-knockout
      mice.
AB  - BACKGROUND: The CC-chemokines (CKs) recruit monocytes/macrophages to sites of
      inflammation; several different CC-CKs play a role in the pathogenesis of
      atherosclerosis. The vaccinia virus expresses a 35-kDa soluble protein (35K) that
      binds to and inactivates nearly all of the CC-CKs, providing a potentially useful
      therapeutic strategy for broad-spectrum CC-CK inhibition in atherosclerosis. A
      recombinant adenovirus encoding soluble 35K (Ad35K) was generated to investigate
      the effect of 35K gene transfer on atherosclerosis in Western diet-fed
      apolipoprotein E-knockout (ApoE KO) mice. METHODS AND RESULTS: ApoE KO mice
      received tail-vein injections of phosphate-buffered saline, Ad35K, or control
      adenovirus AdGFP encoding green fluorescence protein. Two weeks after Ad35K gene
      transfer, atherosclerotic lesion area was significantly reduced in aortic roots
      by 55% compared with PBS or AdGFP control mice (P<0.05). Furthermore, 35K gene
      transfer strikingly reduced the macrophage content in aortic root lesions by 85%
      (P<0.01) and reduced lipid deposition in descending aortas by more than half
      (P<0.05). By an in vitro chemotaxis assay, plasma and aortic homogenates from 35K
      gene transfer mice promoted significantly less CC-CK-induced cell migration than
      did PBS or AdGFP controls. CONCLUSIONS: These findings show that a single
      intravenous injection of a recombinant adenovirus encoding the broad-spectrum CC
      CK inhibitor 35K can reduce atherosclerosis by inhibiting CC-CK-induced
      macrophage recruitment in atherosclerotic ApoE KO mice. These experiments suggest
      that CC-CKs play an important role in atherogenesis and are a rational target for
      therapeutic intervention.

PMID- 15477415
TI  - Left ventricular pacing minimizes diastolic ventricular interaction, allowing
      improved preload-dependent systolic performance.
AB  - BACKGROUND: Left ventricular (LV) pacing improves hemodynamics in patients with
      heart failure. We hypothesized that at least part of this benefit occurs by
      minimization of external constraint to LV filling from ventricular interaction.
      METHODS AND RESULTS: We present median values (interquartile ranges) for 13 heart
      failure patients with LV pacing systems implanted for New York Heart Association
      class III/IV limitation. We used the conductance catheter method to measure LV
      pressure and volume simultaneously. External constraint was measured from the end
      diastolic pressure-volume relation recorded during inferior vena caval occlusion,
      during LV pacing, and while pacing was suspended. External constraint to LV
      filling was reduced by 3.0 (4.6 to 0.6) mm Hg from 4.8 (0.6 to 7.5) mm Hg
      (P<0.01) in response to LV pacing; effective filling pressure (LV end-diastolic
      pressure minus external constraint) increased by 4.0 (2.2 to 5.8) mm Hg from 17.7
      (13.3 to 22.6; P<0.01). LV end-diastolic volume increased by 10 (3 to 11) mL from
      238 (169 to 295) mL (P=0.01), whereas LV end-systolic volume did not change
      significantly (-1 [-2 to 3] mL from 180 [124 to 236] mL, P=0.97), which resulted
      in an increase in stroke volume of 11 (5 to 13) mL from 49 (38 to 59) mL
      (P<0.01). LV stroke work increased by 720 (550 to 1180) mL . mm Hg from 3400
      (2110 to 4480) mL . mm Hg (P=0.01), and maximum dP/dt increased by 120 (2 to 161)
      mm Hg/s from 635 (521 to 767) mm Hg/s (P=0.03). CONCLUSIONS: This study suggests
      a potentially important mechanism by which LV pacing may produce hemodynamic
      benefit. LV pacing minimizes external constraint to LV filling, resulting in an
      increase in effective filling pressure; the consequent increase in LV end
      diastolic volume increases stroke volume via the Starling mechanism.

PMID- 15477416
TI  - Improved prediction of fatal myocardial infarction using the ankle brachial index
      in addition to conventional risk factors: the Edinburgh Artery Study.
AB  - BACKGROUND: Prediction of major cardiovascular and cerebrovascular events using
      conventional risk factor models is limited. Noninvasive measures of subclinical
      atherosclerosis such as the ankle brachial index (ABI) could improve risk
      prediction and provide more focused primary prevention strategies. We wished to
      determine the added value of a low ABI in the prediction of long-term risk of
      cardiovascular and cerebrovascular events and death. METHODS AND RESULTS: In
      1988, 1592 men and women 55 to 74 years of age were randomly selected from the
      age-sex registers of 11 general practices in Edinburgh, Scotland, and followed up
      over a period of 12 years for incident events. After adjustment for age and sex,
      an ABI < or =0.9 was predictive of an increased risk of fatal myocardial
      infarction (MI), cardiovascular death, all-cause death, combined fatal and
      nonfatal MI, and total cardiovascular events. After further adjustment for
      prevalent cardiovascular disease, diabetes, and conventional risk factors, a low
      ABI was independently predictive of the risk of fatal MI. Addition of the ABI
      significantly (P< or =0.01) increased the predictive value of the model for fatal
      MI compared with a model containing risk factors alone. Comparison of areas under
      receiver operator characteristic curves confirmed that a model including the ABI
      discriminated marginally better than one without. CONCLUSIONS: Addition of the
      ABI significantly improved prediction of fatal MI over and above that of
      conventional risk factors. We recommend that the ABI be incorporated into routine
      cardiovascular screening and that the potential of its inclusion into
      cardiovascular scoring systems (with a view to improving their accuracy) now be
      examined.

PMID- 15477417
TI  - Adenoviral gene transfer with soluble vascular endothelial growth factor
      receptors impairs angiogenesis and perfusion in a murine model of hindlimb
      ischemia.
AB  - BACKGROUND: The purpose of the current study was to examine the contribution of
      endogenous vascular endothelial growth factor (VEGF) to ischemia-induced
      angiogenesis and perfusion. METHODS AND RESULTS: C57BL/6J mice (n=28) were
      subjected to unilateral hindlimb ischemia after intravenous injection of
      recombinant adenoviruses (10(9) plaque-forming units) encoding the ligand-binding
      ectodomain of VEGF receptor 1 (VEGFR1/Ad Flt1), VEGF receptor 2 (VEGFR2/Ad Flk1
      Fc), a control murine IgG2alpha Fc fragment (Ad Fc), or vehicle (phosphate
      buffered saline). Hindlimb perfusion was assessed by both laser Doppler and
      fluorescent microsphere injection 10 days after surgery. The role of endogenous
      VEGF in ischemia-induced angiogenesis and arteriogenesis was measured by
      capillary density and microangiography, respectively. Adenoviral gene transfer
      with soluble VEGFRs significantly attenuated hindlimb perfusion as assessed by
      laser Doppler and microsphere analysis (P<0.05). Furthermore, soluble VEGFRs
      significantly reduced ischemia-induced angiogenesis and collateral growth and
      inhibited histological recovery of muscle tissue. Adverse events consistent with
      ongoing vascular insufficiency such as limb necrosis or gangrene were observed
      only in animals expressing soluble VEGFRs and not in control animals.
      CONCLUSIONS: Systemic, soluble receptor-mediated VEGF inhibition indicates an
      essential role for endogenous VEGF during postischemic angiogenesis and hindlimb
      perfusion.

PMID- 15477418
TI  - Electromechanical mapping identifies improvement in function and retention of
      contractile reserve after revascularization in ischemic cardiomyopathy.
AB  - BACKGROUND: We hypothesized that (1) a significant proportion of ischemic
      dysfunctional segments that do not improve function will demonstrate
      postrevascularization contractile reserve and (2) electromechanical mapping (EMM)
      can identify segments that improve function as well as those with
      postrevascularization contractile reserve, a potential indicator of delayed
      functional improvement. METHODS AND RESULTS: Eighteen patients with severe
      ischemic left ventricular dysfunction underwent EMM and dobutamine (D) cardiac
      magnetic resonance imaging (CMR) followed by revascularization. Four months after
      revascularization, all patients underwent a repeated D-CMR, and at 35 months, a
      subgroup (n=6) underwent a third CMR. Of 120 dysfunctional segments, 60 segments
      had improved rest function (IRF) and 60 did not. Twenty-eight of 60 segments
      (47%) that did not improve RF demonstrated postrevascularization contractile
      reserve (CR), and 32 of 60 segments (53%) that demonstrated neither IRF nor CR
      were persistently dysfunctional (PD). CR segments recovered significantly greater
      late function compared with IRF or PD: 14+/-12% vs 2+/-5% and 4+/-7%,
      respectively; P<0.05. EMM ratio, defined as the unipolar voltage divided by
      linear shortening, was significantly higher in IRF segments compared with
      segments that did not improve RF: 2.4+/-4.5 vs 0.7+/-3.5, P<0.05. Unipolar
      voltage was stepwise lower in normal, IRF, CR, and PD segments (10.5+/-4.7, 9.3+/
      3.9, 8.8+/-3.2, and 7.4+/-2.3 mV, respectively; P<0.01 for trend). CONCLUSIONS:
      Almost half of dysfunctional myocardial segments in chronic ischemic heart
      disease that do not improve RF early after revascularization demonstrate early CR
      and delayed functional recovery. EMM parameters can identify segments that
      improve RF and retain CR early after revascularization.

PMID- 15477419
TI  - Prognostic significance of the long pentraxin PTX3 in acute myocardial
      infarction.
AB  - BACKGROUND: Inflammation has a pathogenetic role in acute myocardial infarction
      (MI). Pentraxin-3 (PTX3), a long pentraxin produced in response to inflammatory
      stimuli and highly expressed in the heart, was shown to peak in plasma
      approximately 7 hours after MI. The aim of this study was to assess the
      prognostic value of PTX3 in MI compared with the best-known and clinically
      relevant biological markers. METHODS AND RESULTS: In 724 patients with MI and ST
      elevation, PTX3, C-reactive protein (CRP), creatine kinase (CK), troponin T
      (TnT), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were assayed at
      entry, a median of 3 hours, and the following morning, a median of 22 hours from
      symptom onset. With respect to outcome events occurring over 3 months after the
      index event, median PTX3 values were 7.08 ng/mL in event-free patients, 16.12
      ng/mL in patients who died, 9.12 ng/mL in patients with nonfatal heart failure,
      and 6.88 ng/mL in patients with nonfatal residual ischemia (overall P<0.0001).
      Multivariate analysis including CRP, CK, TnT, and NT-proBNP showed that only age
      > or =70 years (OR, 2.11; 95% CI, 1.04 to 4.31), Killip class >1 at entry (OR,
      2.20; 95% CI, 1.14 to 4.25), and PTX3 (>10.73 ng/mL) (OR, 3.55; 95% CI, 1.43 to
      8.83) independently predicted 3-month mortality. Biomarkers predicting the
      combined end point of death and heart failure in survivors were the highest
      tertile of PTX3 and of NT-proBNP and a CK ratio >6. CONCLUSIONS: In a
      representative contemporary sample of patients with MI with ST elevation, the
      acute-phase protein PTX3 but not the liver-derived short pentraxin CRP or other
      cardiac biomarkers (NT-proBNP, TnT, CK) predicted 3-month mortality after
      adjustment for major risk factors and other acute-phase prognostic markers.

PMID- 15477420
TI  - Prostaglandin E2--mediated relaxation of the ductus arteriosus: effects of
      gestational age on g protein-coupled receptor expression, signaling, and
      vasomotor control.
AB  - BACKGROUND: In the preterm newborn, a patent ductus arteriosus is in large part a
      result of the increased sensitivity of the immature ductus to prostaglandin E2
      (PGE2). PGE2 acts through 3 G protein-coupled receptors (EP2, EP3, and EP4) that
      activate both adenyl cyclase and K(ATP) channels. We explored these pathways to
      identify the mechanisms responsible for the increased sensitivity of the immature
      ductus to PGE2. METHODS AND RESULTS: We measured EP receptor content (mRNA and
      protein), receptor binding, cAMP production, and isometric tension in rings of
      ductus taken from immature (65% gestation) and mature (95% gestation) sheep and
      baboon fetuses. Ductus relaxation and cAMP generation were augmented in response
      to selective EP receptor agonists in the immature ductus. 8-Br-cAMP, a stable
      cAMP analogue, produced greater relaxation in the immature ductus. In the
      presence of a selective protein kinase A inhibitor, Rp-8-CPT cAMPS, the
      developmental differences in sensitivity to PGE2 could no longer be demonstrated.
      EP2, EP3, and EP4 receptor densities were higher in immature ductus, despite
      similar receptor mRNA and protein contents at the 2 gestational ages. In
      contrast, forskolin and NaF, direct activators of adenyl cyclase and Gs,
      respectively, elicited comparable increases in cAMP in both age groups. KATP
      channel inhibition also had similar effects on PGE2-induced relaxation in both
      age groups. CONCLUSIONS: Two mechanisms explain the increased sensitivity of the
      immature ductus to PGE2: (1) increased cAMP production because of increased
      binding of PGE2 to the individual EP receptors and (2) increased potency of cAMP
      on protein kinase A-regulated pathways.

PMID- 15477421
TI  - Vascular endothelial growth factor regulates reendothelialization and neointima
      formation in a mouse model of arterial injury.
AB  - BACKGROUND: The rate of reendothelialization is critical in neointima formation
      after arterial injury. Vascular endothelial growth factor (VEGF), a potent
      endothelial mitogen, has been advocated for accelerating endothelial repair and
      preventing intimal hyperplasia after percutaneous coronary interventions.
      However, the precise mechanism of action of VEGF treatment and the physiologic
      role of endogenous VEGF after arterial injury are not well described. To better
      understand the role of VEGF in arterial repair, we overexpressed both VEGF and a
      soluble, chimeric VEGF receptor (VEGF-trap), which binds free VEGF with high
      affinity, in a mouse model of arterial injury. METHODS AND RESULTS: Four groups
      of C57BL/6 mice underwent denuding endothelial injury 1 day after systemic
      injection of recombinant adenovirus expressing (1) VEGF, (2) VEGF-trap, (3) VEGF
      plus VEGF-trap, or (4) control adenovirus. Circulating levels of adenovirus
      encoded proteins were significantly elevated after gene transfer. VEGF
      overexpression accelerated reendothelialization and increased luminal endothelial
      cell proliferation 2 weeks after arterial injury (P<0.05), resulting in decreased
      neointima formation at 4 weeks compared with control (P<0.01). Cotreatment with
      VEGF-trap completely sequestered free VEGF and abrogated the beneficial effect of
      VEGF overexpression. Interestingly, sequestration of endogenous VEGF by VEGF-trap
      overexpression alone also led to delayed reendothelialization at 2 weeks (P<0.01)
      and increased neointima formation at 4 weeks (P<0.01). CONCLUSIONS: VEGF
      overexpression accelerated endothelial repair and inhibited neointima formation
      after arterial injury. Conversely, sequestration of exogenous and/or endogenous
      VEGF by VEGF-trap delayed reendothelialization and significantly increased
      neointima size. This demonstrates the therapeutic potential of VEGF but also
      emphasizes the important physiologic role of endogenous VEGF in vascular repair.

PMID- 15477422
TI  - Prevention of sudden death in hypertrophic cardiomyopathy: but which
      defibrillator for which patient?

PMID- 15477423
TI  - Images in cardiovascular medicine. High resolution images obtained with
      ultrasound and magnetic resonance imaging of pericarotid fibrosis in Erdheim
      Chester disease.

PMID- 15477424
TI  - Family history, subclinical atherosclerosis, and coronary heart disease risk:
      barriers and opportunities for the use of family history information in risk
      prediction and prevention.

PMID- 15477425
TI  - Insulin-like growth factor-1 as a vascular protective factor.

PMID- 15477426
TI  - Cardiovascular health promotion in the schools: a statement for health and
      education professionals and child health advocates from the Committee on
      Atherosclerosis, Hypertension, and Obesity in Youth (AHOY) of the Council on
      Cardiovascular Disease in the Young, American Heart Association.

PMID- 15477427
TI  - Cracking the problem of back pain: is chiropractic the answer?

PMID- 15477428
TI  - Polypharmacy: a new paradigm for quality drug therapy in the elderly?

PMID- 15477429
TI  - Heparin-induced thrombocytopenia: myths and misconceptions (that will cause
      trouble for you and your patient).

PMID- 15477430
TI  - Risk of venous thromboembolic disease associated with hormonal contraceptives and
      hormone replacement therapy: a clinical review.
AB  - Venous thromboembolic events (VTEs) represent a serious complication related to
      hormonal contraception and hormone replacement therapy (HRT). Evidence on
      hormonal contraceptive- and HRT-related VTEs is derived almost exclusively from
      observational studies and points to a 2- to 6-fold increased relative risk of
      VTEs with either therapy. Oral contraceptive pills that contain third-generation
      progestins (desogestrel or gestodene) seem to be associated with greater VTE risk
      than those that contain levonorgestrel. Oral contraceptive pill use and HRT are
      associated with exponentially higher VTE relative risks when used by women who
      carry an inherited hypercoagulable state. The indication of a lower or a lack of
      VTE risk associated with the use of progestin-only contraceptives and with
      transdermal HRT suggests that these therapies may be safer than combination oral
      contraceptive pills and oral HRT for women in whom oral estrogen therapy is
      considered contraindicated. Data that support such safety advantages are limited
      and should be interpreted with caution.

PMID- 15477431
TI  - A systematic review of the diagnostic accuracy of natriuretic peptides for heart
      failure.
AB  - BACKGROUND: The diagnosis of heart failure is difficult, with both overdiagnosis
      and underdiagnosis occurring commonly in practice. Natriuretic peptides have been
      proposed as a possible test for assisting diagnosis. We assessed the diagnostic
      accuracy of brain natriuretic peptide (BNP), including a comparison with atrial
      natriuretic peptide (ANP). METHODS: Electronic searches were conducted of MEDLINE
      and EMBASE from January 1994 to December 2002 and handsearches of reference lists
      of included studies. We included studies that assessed the diagnostic accuracy of
      BNP against echocardiographic or clinical criteria or that compared the
      diagnostic accuracy of BNP with ANP. Two reviewers assessed studies for inclusion
      and quality and extracted the relevant data. A meta-analysis was performed by
      pooling the diagnostic odds ratios for studies that used a common reference
      standard. RESULTS: Twenty studies were included. For the 8 studies (n = 4086)
      that measured BNP against the criterion of left ventricular ejection fraction of
      40% or less (or equivalent), the pooled diagnostic odds ratio was 11.6 (95%
      confidence interval, 8.4-16.1). The pooled diagnostic odds ratio was greater,
      30.9 (95% confidence interval, 27.0-35.4), in the 7 studies (n = 2374) that
      measured BNP against clinical criteria (generally a consensus view using all
      other clinical information). The diagnostic odds ratio was similar in studies
      conducted in general practice and in hospital settings. Three studies compared
      BNP with N-terminal-ANP, a precursor form of ANP, and pooling of the results of
      these studies showed BNP to be a more accurate marker of heart failure than NT
      ANP. CONCLUSIONS: Brain natriuretic peptide is an accurate marker of heart
      failure. Use of a cutoff value of 15 pmol/L achieves high sensitivity, and BNP
      values below this exclude heart failure in patients in whom disease is suspected.
      As the diagnostic odds ratio for BNP is greater when assessed against clinical
      criteria than against left ejection fraction alone, BNP may also be detecting
      patients with "diastolic" heart failure.

PMID- 15477432
TI  - Comparative analysis of individuals with and without chiropractic coverage:
      patient characteristics, utilization, and costs.
AB  - BACKGROUND: Back pain accounts for more than $100 billion in annual US health
      care costs and is the second leading cause of physician visits and
      hospitalizations. This study ascertains the effect of systematic access to
      chiropractic care on the overall and neuromusculoskeletal-specific consumption of
      health care resources within a large managed-care system. METHODS: A 4-year
      retrospective claims data analysis comparing more than 700 000 health plan
      members with an additional chiropractic coverage benefit and 1 million members of
      the same health plan without the chiropractic benefit. RESULTS: Members with
      chiropractic insurance coverage, compared with those without coverage, had lower
      annual total health care expenditures ($1463 vs $1671 per member per year,
      P<.001). Having chiropractic coverage was associated with a 1.6% decrease (P =
      .001) in total annual health care costs at the health plan level. Back pain
      patients with chiropractic coverage, compared with those without coverage, had
      lower utilization (per 1000 episodes) of plain radiographs (17.5 vs 22.7,
      P<.001), low back surgery (3.3 vs 4.8, P<.001), hospitalizations (9.3 vs 15.6,
      P<.001), and magnetic resonance imaging (43.2 vs 68.9, P<.001). Patients with
      chiropractic coverage, compared with those without coverage, also had lower
      average back pain episode-related costs ($289 vs $399, P<.001). CONCLUSIONS:
      Access to managed chiropractic care may reduce overall health care expenditures
      through several effects, including (1) positive risk selection; (2) substitution
      of chiropractic for traditional medical care, particularly for spine conditions;
      (3) more conservative, less invasive treatment profiles; and (4) lower health
      service costs associated with managed chiropractic care. Systematic access to
      managed chiropractic care not only may prove to be clinically beneficial but also
      may reduce overall health care costs.

PMID- 15477433
TI  - Alcohol and risk of atrial fibrillation or flutter: a cohort study.
AB  - BACKGROUND: The evidence for an association between alcohol consumption and risk
      of atrial fibrillation is conflicting. METHODS: We prospectively examined the
      association between alcohol consumption and risk of atrial fibrillation or
      flutter among 47 949 participants (mean age, 56 years) in the Danish Diet,
      Cancer, and Health Study. The consumption of alcohol was analyzed as sex-specific
      quintiles by Cox proportional hazards regression models. RESULTS: The mean +/- SD
      consumption of alcohol per day was 28.2 +/- 25 g in men and 13.9 +/- 15 g in
      women. During follow-up (mean, 5.7 years), atrial fibrillation or flutter
      developed in 556 subjects (374 men and 182 women). After adjusting for
      established risk factors, there was a modest increase in risk of atrial
      fibrillation or flutter by increasing alcohol consumption in men. When using the
      lowest quintile of alcohol consumption in men as a reference, the adjusted hazard
      rate ratios in men in quintiles 2, 3, 4, and 5 were 1.04, 1.44, 1.25, and 1.46,
      respectively (P for trend, .04). When using the lowest quintile of alcohol
      consumption in women as a reference, the adjusted hazard rate ratios in women in
      quintiles 2, 3, 4, and 5 were 1.09, 1.27, 1.23, and 1.14, respectively (P for
      trend, .69). Inclusion of information on the frequency of alcohol consumption and
      the preferred source of alcohol did not change these associations. CONCLUSIONS:
      Consumption of alcohol was associated with an increased risk of atrial
      fibrillation or flutter in men. In women, moderate consumption of alcohol did not
      seem to be associated with risk of atrial fibrillation or flutter.

PMID- 15477434
TI  - Talking with terminally ill patients and their caregivers about death, dying, and
      bereavement: is it stressful? Is it helpful?
AB  - BACKGROUND: Discussing end-of-life issues with terminally ill patients is often
      considered distressing and harmful. This study was conducted to assess whether
      interviewing terminally ill patients and their caregivers about death, dying, and
      bereavement is stressful and/or helpful. METHODS: Patients from 6 sites in the
      United States who were estimated to have 6 months or less to live were
      interviewed in person and reinterviewed 2 to 6 months later. Their caregivers
      were interviewed separately. At the end of the interviews, patients and
      caregivers were asked how stressful and how helpful the interview had been. Of
      1131 eligible patients, 988 (87.4%) were interviewed, and of 915 eligible
      caregivers, 893 (97.6%) were interviewed. RESULTS: At the end of the first
      interview, 1.9% of the patients reported having experienced a great deal of
      stress, 7.1% some stress, and 88.7% little or no stress from the interview. Among
      the caregivers, 1.5% reported a great deal of stress, 8.4% some stress, and 89.7%
      little or no stress. Slightly more stress was reported to have been caused by the
      reinterview. Overall, 16.9% of the patients reported the initial interview as
      very helpful, 29.6% as somewhat helpful, and 49.6% as offering little or no help.
      Among the caregivers, 19.1% reported the initial interview as very helpful, 34.3%
      as somewhat helpful, and 44.9% as offering little or no help. The reported
      helpfulness of the second interview was slightly less. Patients experiencing pain
      (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.02-1.56), more personal
      meaning in dying (OR, 3.05; 95% CI, 2.02-4.59), and less ease with talking about
      the end of life (OR, 1.32; 95% CI, 1.09-1.60) were significantly more likely to
      report stress. Patients who were from an ethnic minority (OR, 1.85; 95% CI, 1.31
      2.63), anxious about the end of their life (OR, 1.39; 95% CI 1.16-1.67), more
      spiritual (OR, 1.30; 95% CI, 1.06-1.61), and serene (OR, 1.25; 95% CI, 1.08-1.45)
      were significantly more likely to report the interview helpful. There was no
      relationship between stress and helpfulness. CONCLUSIONS: Terminally ill patients
      and their caregivers can discuss death, dying, and bereavement in a structured
      interview with minimal stress and report that the interview was helpful.
      Institutional review boards should not preemptively restrict surveys with
      terminally ill patients without reliable evidence that they will be stressful or
      otherwise harmful.

PMID- 15477435
TI  - Insulin therapy for critically ill hospitalized patients: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Hyperglycemia is common in critically ill hospitalized patients, and
      it is associated with adverse outcomes, including increased mortality. The
      objective of this meta-analysis was to determine the effect of insulin therapy
      initiated during hospitalization on mortality in adult patients with a critical
      illness. METHODS: An electronic search in the English-language articles of
      MEDLINE and the Cochrane Controlled Clinical Trials Register and a hand search of
      key journals and relevant review articles were performed. Randomized controlled
      trials that reported mortality data on critically ill hospitalized adult patients
      who were treated with insulin were selected. Data on patient demographics,
      hospital setting, intervention (formulation and dosage of insulin, delivery
      method, and duration of therapy), mortality outcomes, adverse events, and
      methodological quality were extracted. RESULTS: Thirty-five trials met the
      inclusion criteria. Combining data from all trials using a random-effects model
      showed that insulin therapy decreases short-term mortality by 15% (relative risk
      [RR], 0.85; 95% confidence interval [CI], 0.75-0.97). In subgroup analyses,
      insulin therapy decreased mortality in the surgical intensive care unit (RR,
      0.58; 95% CI, 0.22-0.62), when the aim of therapy was glucose control (RR, 0.71;
      95% CI, 0.54-0.93), and in patients with diabetes mellitus (RR, 0.73; 95% CI,
      0.58-0.90). A near-significant trend toward decreasing mortality was seen in
      patients with acute myocardial infarction who did not receive reperfusion therapy
      (RR, 0.84; 95% CI, 0.71-1.00). No randomized trials of insulin in the medical
      intensive care unit were identified. CONCLUSION: Insulin therapy initiated in the
      hospital in critically ill patients has a beneficial effect on short-term
      mortality in different clinical settings.

PMID- 15477436
TI  - Antibiotics for anthrax: patient requests and physician prescribing practices
      during the 2001 New York City attacks.
AB  - BACKGROUND: Little is known about patient encounters with primary care physicians
      and prescribing practices during the 2001 US anthrax attacks. METHODS: We
      retrospectively reviewed the electronic medical record of outpatient telephone
      and clinic visits at a large primary care practice in New York City from
      September 11 to December 31, 2001, to identify physician- and patient-related
      factors that were associated with prescribing antibiotics for anthrax
      prophylaxis. RESULTS: Average daily patient volume from October to December was
      higher in 2001 (221.2 patients per day) compared with 2000 (199.1; P<.01) and
      2002 (215.8; P = .14). Patient-initiated discussion about anthrax or smallpox
      were involved in 244 patient contacts with 63 physicians, including 92 (0.6%) of
      14917 telephone contacts and 152 (1.0%) of 15 539 office visits. Fifty patients
      (21%) requested antibiotics or vaccines and 52 (22%) received antibiotics: 39
      received ciprofloxacin; 12, doxycycline; and 1, both drugs. Independent
      predictors of receiving anthrax prophylaxis included requesting medication (odds
      ratio [OR], 8.1; 95% confidence interval [CI], 3.5-18.6), reporting powder or
      workplace exposure (OR, 4.5; 95% CI, 2.1-10.0), having an abnormal physical
      examination finding (OR, 3.9; 95% CI, 1.4-11.0), and being asymptomatic
      (reporting any illness symptoms was associated with an OR of 0.3 [95% CI, 0.1
      0.6]). CONCLUSIONS: Primary care physicians played an important and heretofore
      underdocumented role in responding to the 2001 anthrax attacks. Prescription of
      prophylactic antibiotics for anthrax was uncommon and appears to have been
      selective among concerned patients. These results highlight the importance of
      including primary care physicians in community-wide bioterrorism response
      planning.

PMID- 15477437
TI  - Efficacy and safety of a topical diclofenac solution (pennsaid) in the treatment
      of primary osteoarthritis of the knee: a randomized, double-blind, vehicle
      controlled clinical trial.
AB  - BACKGROUND: Oral nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used
      to relieve the symptoms of osteoarthritis (OA) but can produce harmful systemic
      effects and end-organ damage. A topical NSAID formulation may provide symptom
      relief with fewer adverse effects. A new topical diclofenac sodium solution
      containing the absorption enhancer dimethyl sulfoxide-was evaluated for the
      relief of the symptoms of primary OA of the knee. METHODS: A total of 326
      patients met entry criteria (including abnormal radiographic findings and flare
      of pain) and were randomized to receive 40 drops of topical diclofenac solution
      or a vehicle-control solution, 4 times daily, for 12 weeks. We evaluated 3
      primary outcome measures, the Western Ontario McMaster Universities LK3.1 OA
      Index (WOMAC) pain and physical function subscales and a patient global
      assessment, and 2 other measures, stiffness and pain on walking, at baseline and
      after final application. We assessed safety by evaluation of adverse events,
      vital signs, and irritation at the application site. RESULTS: Topical diclofenac
      solution was significantly more effective than the vehicle-control solution for
      all outcome measures; pain, P = .001; physical function, P = .002; patient global
      assessment, P = .003; stiffness, P = .005; and pain on walking, P = .004. Among
      patients receiving topical diclofenac, self-limiting minor skin irritation
      occurred in 68 (41.5%) of 164 patients, including dryness in 60 (36.6%), rash in
      18 (11.0%), and paresthesia, pruritus, and vesiculobullous rash in 1 (0.6%) each.
      There was no significant difference between groups in NSAID-related
      gastrointestinal tract complaints or in dropouts due to study-related adverse
      effects. CONCLUSION: Topical diclofenac is effective in the treatment of the
      symptoms of primary OA of the knee, with only minor local irritation and no
      significant systemic adverse events.

PMID- 15477438
TI  - Sustained vertebral fracture risk reduction after withdrawal of teriparatide in
      postmenopausal women with osteoporosis.
AB  - BACKGROUND: Teriparatide (recombinant human parathyroid hormone [1-34]) reduces
      fracture risk in postmenopausal women with osteoporosis. We assessed the safety
      and incidence of new vertebral fractures after withdrawal of teriparatide.
      METHODS: This study is a follow-up to the Fracture Prevention Trial (FPT), a
      randomized, placebo-controlled study of postmenopausal women with osteoporosis
      treated with teriparatide (20 or 40 microg) once daily for a mean of 18 months.
      More than 90% of the women remaining at the end of the FPT continued into the
      follow-up study (n = 1262). Patients and investigators were unblinded to original
      treatment group assignment. Women were treated according to standard clinical
      practice, including elective use of osteoporosis drugs. New vertebral fractures
      were determined by semiquantitative scoring of lateral thoracic lumbar spine
      radiographs 18 months after the end of the FPT. RESULTS: During the follow-up
      study, the reduction in fracture risk associated with previous treatment with
      teriparatide, 20 and 40 microg, was 41% (P = .004) and 45% (P = .001),
      respectively, vs placebo. The absolute reduction from the FPT baseline to the 18
      month follow-up visit was 13% for both doses. Osteoporosis drugs were used by 47%
      of women during follow-up, with greater use in the former placebo group (P =
      .04); nevertheless, persistent fracture protection of previous teriparatide
      therapy was evident. Post hoc analysis also suggests that teriparatide treatment
      substantially reduced the increased risk of subsequent fracture in women who
      sustained a fracture during the FPT (P = .05). CONCLUSION: Vertebral fracture
      risk reduction by teriparatide administration persists for at least 18 months
      after discontinuation of therapy.

PMID- 15477439
TI  - Medication undertreatment in assisted living settings.
AB  - BACKGROUND: Residential care/assisted living (RC/AL) is a rapidly growing, long
      term care setting, where medication use has not been carefully examined. We
      sought to determine the prevalence and predictors of nonprescribing of selected
      medications whose value in decreasing morbidity has been established in clinical
      trials. METHODS: As part of a survey of a stratified random sample of 193 RC/AL
      facilities in Florida, Maryland, New Jersey, and North Carolina, data were
      gathered on 2014 residents 65 years and older. Patient characteristics and
      diagnoses were recorded based on medical record reviews and in-person patient
      assessments; all medications administered at least 4 of the previous 7 days were
      recorded. Data on facility characteristics were obtained by interviewing facility
      administrators. Bivariate and multivariate logistic regression was performed to
      identify associations between medication nonprescribing and facility
      characteristics, physician visitation, and patient age, sex, race, comorbidity,
      functional dependency, and cognition. RESULTS: Of 328 subjects with congestive
      heart failure, 204 (62.2%) were not receiving an angiotensin-converting enzyme
      inhibitor; of 172 subjects with prior myocardial infarction, 60.5% were not
      receiving aspirin and 76.2% were not receiving beta-blockers; of 435 patients
      with history of stroke, 37.5% were not receiving an anticoagulant or antiplatelet
      agent; and of 315 patients with osteoporosis, 61.0% were not receiving calcium
      supplementation and 51.1% were not receiving any treatment for the condition.
      Resident age, race, sex, comorbidity, cognitive status, and dependency in
      activities of daily living were rarely associated with nonprescribing; in
      contrast, facility factors-particularly facility type and the frequency of
      physician visits-were somewhat more frequently associated with nonprescribing.
      CONCLUSIONS: Undertreatment appears to be prevalent in RC/AL facilities. Since
      preserving independence is often a primary goal of care in these settings, more
      attention may need to be paid to the use of treatments that have been shown to
      reduce long-term morbidity.

PMID- 15477440
TI  - Comprehensive strategy to prevent nosocomial spread of methicillin-resistant
      Staphylococcus aureus in a highly endemic setting.
AB  - BACKGROUND: The effectiveness and feasibility of a comprehensive strategy to
      reduce nosocomial transmission of methicillin-resistant Staphylococcus aureus
      (MRSA) in a highly endemic setting have not yet been proved. Limited benefits and
      the high cost of such programs are the main concerns. METHODS: We prospectively
      evaluated the effect of an aggressive infection control program on transmission
      of MRSA in the University Clinic of Respiratory and Allergic Diseases. All
      patients with MRSA carriage during 5 years (January 1, 1998, through December 31,
      2002) were included and categorized into imported or hospital-acquired cases.
      RESULTS: Methicillin-resistant S aureus was recovered from 223 hospitalized
      patients; 142 cases were imported and 81 were acquired at our institution. After
      introduction of the comprehensive infection control program in 1999, the annual
      incidence of MRSA carriage per 1000 admissions increased from 4.5 in 1998 to 8.0
      in 1999 (P = .02), and remained stable thereafter. In this period, the proportion
      of MRSA cases acquired in our institution decreased from 50.0% in 1999 to 6.1% in
      2002 (P<.001), whereas the proportion of MRSA cases transferred from other
      hospitals (P<.001) and nursing homes (P = .03) increased. All 19 MRSA carriers
      with 3 sets of follow-up cultures were successfully decolonized. CONCLUSIONS:
      With a comprehensive infection control program, it was possible to reduce
      nosocomial transmission of MRSA in a highly endemic setting. With good hand
      hygiene using alcohol handrub, early detection, isolation, and a decolonization
      strategy, containment of MRSA was achievable, despite a high rate of transferred
      patients with MRSA.

PMID- 15477441
TI  - Safety of anticoagulation therapy in well-informed older patients.
AB  - BACKGROUND: In older populations, oral anticoagulation therapy (OAT) is underused
      by physicians, mainly because of fear of bleeding complications. The aim of this
      study was to determine the incidence of bleeding complications and associated
      risk factors in a large heterogeneous group of older patients. METHODS: Combined
      retrospective and prospective cohort study conducted in geriatric and internal
      medicine departments. All patients 80 years or older discharged with the
      recommendation of OAT were followed up for a mean +/- SD of 28.8 +/- 36.3 months.
      The rate of bleeding events and the quality of anticoagulation were compared
      across a wide range of demographic and clinical variables and cognitive and
      functional status. In addition, we assessed the quality of education given to the
      patient or caregiver on the use of OAT. RESULTS: Among 15 387 patients 80 years
      or older, 323 (2.1%) were discharged with the recommendation of OAT. The rate of
      major bleedings was 2.4 events per 1000 patient-months. Socioeconomic and
      cognitive variables and functional impairments were not associated with an
      increased rate of bleeding. In multivariate analysis, insufficient education on
      OAT as perceived by the patient or caregiver (odds ratio [OR], 8.83),
      polypharmacy (OR, 6.14), and international normalized ratio values above the
      therapeutic range (OR, 1.08) were the only significant predictive factors for
      bleeding complications. CONCLUSIONS: The rate of bleeding complications,
      especially major bleedings, was low in this large group of older patients, many
      with comorbidities and cognitive and functional impairments. Insufficient OAT
      education was the major factor that predicted bleeding. Therefore, improving and
      fostering better methods of OAT education may further reduce bleeding
      complications.

PMID- 15477442
TI  - Absence of interaction between atorvastatin or other statins and clopidogrel:
      results from the interaction study.
AB  - BACKGROUND: Some, but not all, post hoc analyses have suggested that the
      antiplatelet effects of clopidogrel are inhibited by atorvastatin. We sought to
      address this issue prospectively by performing serial measurements of 19 platelet
      characteristics using conventional aggregometry, rapid analyzers, and flow
      cytometry. METHODS: The Interaction of Atorvastatin and Clopidogrel Study
      (Interaction Study) was designed for patients undergoing coronary stenting. All
      patients (n = 75) received 325 mg of aspirin daily for at least 1 week and 300 mg
      of clopidogrel immediately prior to stent implantation. They had been taking
      atorvastatin (n = 25), any other statin (n = 25), or no statin (n = 25) for at
      least 30 days prior to stenting. The main outcome measure was comparison of
      platelet biomarkers 4 and 24 hours after clopidogrel administration between study
      groups. RESULTS: At baseline, patients from both statin groups exhibited
      diminished platelet aggregation and reduced platelet expression of G-protein
      coupled protease-activated thrombin receptor (PAR)-1. There were no significant
      differences in measured platelet characteristics among the study groups 4 and 24
      hours after clopidogrel intake, with the exception of a lower collagen-induced
      aggregation at 24 hours and a constantly diminished expression of PAR-1 in
      patients treated with any statin. CONCLUSIONS: Statins in general, and
      atorvastatin in particular, do not affect the ability of clopidogrel to inhibit
      platelet function in patients undergoing coronary stenting. These prospective
      data also suggest that statins may inhibit platelets directly via yet unknown
      mechanism(s) possibly related to the regulation of the PAR-1 thrombin receptors.

PMID- 15477443
TI  - Symptoms and treatment burden of gastroesophageal reflux disease: validating the
      GERD assessment scales.
AB  - BACKGROUND: A comprehensive assessment instrument that measures the burden of
      both symptoms and treatment is needed to determine the optimal management of
      gastroesophageal reflux disease (GERD), and we developed such an instrument.
      METHODS: This validation study included 3 groups: patients with active GERD (n =
      193), surgical patients with prior GERD (n = 197), and general medical
      outpatients (n = 63). All completed an initial survey. General medical patients
      and patients with active GERD were resurveyed after 2 to 6 weeks. The main
      outcome measures were test-retest reliability, internal consistency, discriminant
      validity, and responsiveness to change for 3 scales graduated from 0 to 100: a
      GERD burden (or overall impact on quality of life scale), a symptoms scale, and a
      treatment scale. Higher scores indicated greater disease burden. RESULTS: The
      GERD burden, symptoms, and treatment scales all demonstrated good discriminant
      validity, as patients in the active-GERD group had the highest scores. Scores on
      each scale effectively classified the patients who belonged to the active-GERD
      group. Moreover, scores improved substantially 8 weeks after surgery, thereby
      demonstrating the scales' responsiveness to change. As hypothesized, the burden
      of treatment was distinct from that of symptoms, as 23% of patients not bothered
      by GERD symptoms described their GERD treatment to be a moderate or serious
      problem. Indeed, the impact of treatment problems approached that of symptoms
      problems. All pairwise comparisons were significant (P<.02). CONCLUSIONS: The
      GERD burden, symptoms, and treatment scales were valid, reliable, and responsive
      instruments for use in patients with GERD. Our analyses highlight the importance
      of assessing both symptoms and treatment burden in patients with GERD.

PMID- 15477444
TI  - Don't forget to prescribe exercise for your older patients.

PMID- 15477445
TI  - Chronic fatigue syndrome, pregnancy, and Addison disease.

PMID- 15477446
TI  - Prescribing exercise: is your physician's head in the game?

PMID- 15477447
TI  - The obesity epidemic.

PMID- 15477448
TI  - Key to weight loss--more than exercise?

PMID- 15477449
TI  - Efficacy and safety of sildenafil in patients with congestive heart failure.

PMID- 15477450
TI  - Putting an obesity "call to action" into action.

PMID- 15477451
TI  - Use of sildenafil is safe in men with congestive heart failure.

PMID- 15477452
TI  - Acanthamoeba keratitis in non-contact lens wearers in India: DNA typing-based
      validation and a simple detection assay.
AB  - OBJECTIVES: To establish that the protozoan Acanthamoeba is one of the causative
      organisms associated with non-contact lens-related keratitis in the Indian
      population and to develop a simple and sensitive diagnostic assay for clinical
      testing. DESIGN: DNA sequencing of nuclear 18S and 26S ribosomal DNA motifs was
      performed and compared with the reference Acanthamoeba strains, to establish the
      genetic identity of the putative amoeba isolates obtained from the corneal
      scrapings of non-contact lens-wearing patients with keratitis. Ribosomal DNA
      typing of clinical corneal scrapings from the patients with keratitis was
      performed by means of a simple agarose gel-based multiplex polymerase chain
      reaction assay, to detect the cases of Acanthamoeba keratitis. RESULTS: The
      ribosomal DNA analysis of 15 putative amoeba isolates obtained from the corneal
      scrapings of 14 patients with keratitis and 1 from the patients' environment
      established the isolates to be pathogenic formsof Acanthamoeba belonging to type
      T4 ribosomal DNA genotype. Multiplex polymerase chain reaction assay was specific
      and sensitive enough to detect as low as 5 pg of Acanthamoeba DNA. Its utility as
      a reliable diagnostic assay was demonstrated directly with the use of 34
      additional corneal scrapings. CONCLUSIONS: Acanthamoeba is one of the causative
      organisms of keratitis in Indian patients with no history of contact lens usage.
      Moreover, the Acanthamoeba infection can be easily detected in the clinical
      samples by means of the simple multiplex polymerase chain reaction assay based on
      ribosomal DNA typing. Clinical Relevance This study suggests the need and means
      to determine the incidence and prevalance of Acanthamoeba keratitis in India and
      elsewhere. Moreover, the polymerase chain reaction assay would help in early and
      definitive diagnosis, leading to better prognosis of Acanthamoeba keratitis
      condition.

PMID- 15477453
TI  - Outcome of rotational keratoplasty: comparison of endothelial cell loss in
      autografts vs allografts.
AB  - BACKGROUND: The nature of chronic endothelial cell loss in homologous corneal
      grafts is still unclear. Possible causes are cell migration to the recipient bed
      and chronic subclinical immune reaction. OBJECTIVES: To compare endothelial cell
      loss after autologous rotational keratoplasty and homologous keratoplasty and
      present the clinical outcome of patients after rotational keratoplasty. METHODS:
      In this open prospective study, we included 7 consecutive patients who underwent
      rotational keratoplasty between 1998 and 2000 in our hospital. Patients were
      examined clinically every 3 months, and visual acuity, astigmatism, and
      endothelial cell density were evaluated. Endothelial cell densities were compared
      with endothelial cell counts of 293 homologous keratoplasties. RESULTS: Mean
      follow-up for autologous grafts was 39 months. Mean increase in visual acuity was
      3.5 lines. Mean astigmatism was 4.75 diopters in the autologous graft group. Mean
      preoperative endothelial cell density was 2058 (637 cells/mm(2)). Mean
      endothelial cell density after 1 year was 1865 (639 cells/mm(2)), which
      represents a mean +/- SD cell loss of 15% +/- 7.19%. At the end of follow-up,
      endothelial cell number after autologous grafting was 1630 +/- 622 cells/mm(2).
      Endothelial cell loss after 1 year in homologous grafts was 40% +/- 21.34%. There
      was 1 decompensation of autologous graft in the follow-up period. Main Outcome
      Measure Comparison of endothelial cell count at different postoperative time
      points using nonpaired t test. CONCLUSIONS: Endothelial cell loss in autologous
      grafts is significantly lower than in homologous grafts, which supports the
      hypothesis that chronic endothelial cell loss is due to chronic subclinical
      immune reactions in homologous grafts. Autologous keratoplasties can lead to good
      functional results and can be superior to homologous corneal grafting in suitable
      situations.

PMID- 15477454
TI  - Intracorneal inlay complicated by intrastromal epithelial opacification.
AB  - OBJECTIVE: To report epithelial perilenticular opacity as a new complication of
      intracorneal inlay implantation for the correction of hyperopia. DESIGN:
      Prospective observational case series. PARTICIPANTS: Eleven eyes of 7 patients
      underwent intracorneal inlay implantation for the correction of hyperopia.
      METHODS: Intracorneal inlays were implanted onto the stromal bed by using a
      microkeratome cut to create an inferior hinged corneal flap. MAIN OUTCOME
      MEASURES: Postoperative complication occurrence of intracorneal perilenticular
      opacity, microbiological laboratory analysis, histopathological analysis, and
      confocal microscopy study. RESULTS: Of 11 implanted eyes, 5 showed diffuse
      perilenticular opacity of varying intensity that was unresponsive to steroid use
      following intracorneal inlay implantation. All patients had moderate to severe
      loss of best-corrected visual acuity. The inlays showed deposits at the edge and
      on the surface. Confocal microscopy in all eyes produced images compatible with
      the confocal morphologic features of epithelial cells. Explantation of inlays was
      performed in 5 eyes. The histopathologic study showed the presence of epithelial
      cells, and microbiological analysis and cultures were negative for bacteria,
      fungi, and mycobacteria. CONCLUSION: Epithelial perilenticular opacity is a new
      and serious complication in patients with intracorneal inlay implantation for the
      correction of hyperopia.

PMID- 15477455
TI  - Visual field defects after intravitreous administration of indocyanine green in
      macular hole surgery.
AB  - OBJECTIVES: To report the findings on a patient cohort with visual field defects
      after macular hole surgery with indocyanine green (ICG)-assisted internal
      limiting membrane peeling and to investigate the correlation between the defects
      and the use of ICG. DESIGN: Retrospective, noncomparative interventional case
      series. PARTICIPANTS: Thirty-nine eyes of 38 patients having the clinical
      diagnosis of a macular hole who underwent pars plana vitrectomy between January
      1, 2001, and December 31, 2002, were enrolled in this study. INTERVENTION:
      Indocyanine green-assisted internal limiting membrane peeling was performed on a
      series of 22 eyes: 12 eyes using a 0.5% ICG solution and 3-minute exposure to the
      retina (group 1), 4 eyes using a 0.5% ICG solution and immediate washout (group
      2), and 6 eyes using a 0.25% ICG solution and immediate washout (group 3). The
      remaining 17 eyes underwent vitrectomy without ICG-assisted internal limiting
      membrane peeling (group 4). MAIN OUTCOME MEASURES: Visual field, best-corrected
      visual acuity, and fundus photography were evaluated. RESULTS: Postoperatively,
      all patients (100%) in group 1 and 1 (25%) of 4 eyes in group 2 had visual field
      defects. None of the patients in group 3 had a visual field defect. The visual
      field defects included 10 eyes (84%) with nasal defects, 1 eye (8%) with an
      inferotemporal defect, and 1 eye (8%) with an extensive visual field defect.
      Ophthalmoscopy revealed mild to moderate optic disc pallor in 8 (62%) of 13 eyes
      with postoperative visual field defects. Only 1 patient in group 4 had an
      inferotemporal defect; none of the other patients in group 4 had visual field
      defects. There was no statistically significant difference in postoperative
      visual acuity between patients with and without postoperative visual field
      defects. CONCLUSIONS: Although this study was limited by the few patients
      enrolled, our experience indicates that visual field defects, specifically nasal
      defects, can occur after macular hole surgery with ICG-assisted internal limiting
      membrane peeling, and that the incidence depends on the concentration of the ICG
      solution and/or the exposure time to the retina. Further studies are needed to
      clarify the pathomechanism of visual field defects.

PMID- 15477456
TI  - Optical coherence tomography findings in myopic traction maculopathy.
AB  - OBJECTIVE: To describe the features and incidence of epiretinal traction and
      related retinal damage in degenerative myopia. DESIGN: Consecutive observational
      case series. METHODS: We retrospectively reviewed medical records and optical
      coherence tomography findings of 218 eyes with high myopia of 121 consecutive
      patients to detect the incidence and features of epiretinal traction-related
      macular damage. The degree of myopia ranged from -8 to -26 spherical equivalent
      (mean +/- SD, -16.93 +/- 5.74). Mean +/- SD axial length was 29.75 +/- 2.12 mm.
      Excluding eyes with possibly confounding features, 125 eyes were analyzed. MAIN
      OUTCOME MEASURE: Detection of epiretinal traction and related macular damage.
      RESULTS: Epiretinal traction was found in 58 (46.4%) of 125 eyes and retinal
      damage, in 43 eyes (34.4%). Macular retinoschisis was the most frequent form of
      macular damage (25 eyes [58%]), followed by retinal thickening, lamellar hole,
      and shallow retinal detachment. CONCLUSIONS: Epiretinal traction is a frequent
      finding in degenerative myopia and, particularly if associated with the presence
      of staphyloma, can generate a form of macular damage unique to eyes with high
      myopia. This damage can affect up to one third of these eyes and should be
      considered as a separate cause of visual loss easily detected by optical
      coherence tomography at its early stages.

PMID- 15477457
TI  - Tomographic and multifocal electroretinographic features of idiopathic epimacular
      membranes.
AB  - OBJECTIVE: To determine the relationship between the tomographic and
      electrophysiologic characteristics of the retina with an idiopathic epimacular
      membrane. METHODS: Sixty patients with unilateral idiopathic epimacular membranes
      underwent optical coherence tomography and multifocal electroretinography
      (mfERG). The mfERGs were elicited by a pseudorandom m-sequence stimulus with 37
      hexagonal elements, and the mfERGs in area 1 (central 4.1 degrees ), area 2 (ring
      from 4.10 degrees -7.15 degrees ), and area 3 (ring from 7.15 degrees -13.75
      degrees ) were compared with the tomographic features of the corresponding area.
      The data from the normal fellow eyes served as control. MAIN OUTCOME MEASURES:
      The retinal thickness, amplitudes, and implicit time of the mfERG. RESULTS: On
      optical coherence tomographs, the retina was thickest in area 1, followed by area
      2 with low tissue reflectivity of the outer retina, and area 3 was of normal
      thickness. Electroretinography showed the amplitude ratio (affected vs fellow
      eyes) of mfERGs from areas 1, 2, and 3 was significantly lower than that of the
      controls (P<.01), and the implicit times were significantly delayed (P<.01). The
      amplitude ratio was reduced the most in area 1, and the implicit time was delayed
      the most in area 3. The foveal thickness was negatively correlated with visual
      acuity (rho = -0.46; P<.001). The mfERG amplitude in area 1 was not significantly
      correlated with the visual acuity. CONCLUSIONS: It is likely that retinal
      thickness is correlated with neural dysfunction, but mfERGs demonstrated various
      physiological changes in the retina.

PMID- 15477458
TI  - Low-dose proton beam therapy for circumscribed choroidal hemangiomas.
AB  - OBJECTIVE: To evaluate the efficacy and safety of proton beam therapy for
      complicated circumscribed choroidal hemangiomas. METHODS: The study was a
      retrospective nonrandomized investigation. Seventeen consecutive patients,
      referred to the Institut Gustave-Roussy, Villejuif, France, for circumscribed
      choroidal hemangioma associated with serous retinal detachment were studied. Each
      eye received a total dose of 20 cobalt gray equivalents (CGEs) delivered in 15
      second fractions of 5 CGEs over 4 days. Functional tests included the initial and
      final best-corrected visual acuity, slitlamp examination, intraocular pressure,
      fundus examination, fluorescein angiography, and indocyanine green angiography.
      Tumor thickness was determined on B-scan ultrasonography. RESULTS: The macula was
      involved in 7 eyes and the lesion was juxtapapillary in 2 eyes. The mean (SD)
      tumor thickness was 3.06 (9.0) mm. The mean initial tumor diameter was 6.82 mm
      (range, 3.2-12.1 mm). The right eye was involved in 7 cases and the left eye in
      10 cases. The mean (SD) follow-up period was 52 (58) months (range, 36-90
      months). Retinal reattachment was obtained in all cases after a mean period of 2
      months (range, 1-12 months; median, 1 month). Tumor regression was obtained in
      all cases. One recurrence occurred 1 year after the initial treatment in an
      undertreated area. After re-treatment, however, resolution of the retinal
      detachment occurred, and flattening of the choroidal lesion was obtained. Final
      visual acuity improved to 2 Snellen lines or more in 16 eyes (94%), was stable in
      1 eye, and attained 20/40 or more in 12 eyes (70.6%). No radiation therapy
      complications occurred during follow-up. CONCLUSIONS: Proton beam therapy for
      choroidal hemangiomas seems to be an effective and safe alternative option. A
      total dose of 20 CGEs delivered in 4 daily 15-second fractions of 5 CGEs seems
      adequate for local control of both the tumor and serous retinal detachment.

PMID- 15477459
TI  - The effect of ocular warming on ocular circulation in healthy humans.
AB  - OBJECTIVE: To examine the effect of ocular warming on retinal blood flow (RBF)
      and subfoveal choroidal blood flow (CBF) in humans. METHODS: Ocular warming was
      induced in 10 healthy volunteers using an ocular warming lamp for 10 minutes. The
      ocular surface temperature was measured before and after warming. The RBF in the
      retinal artery and vein and the CBF in the foveal region were examined with a
      retinal laser Doppler velocimetry system and a laser Doppler flowmeter,
      respectively. Ocular blood flow measurements were performed before and 3, 6, and
      9 minutes after warming. RESULTS: The ocular surface temperature significantly
      increased just after warming and returned to baseline 10 minutes later. Three
      minutes after warming, the mean +/- SE RBF significantly increased in the retinal
      artery (14.2% +/- 3.5%, P = .01) and vein (15.8% +/- 3.6%, P = .006). Six minutes
      after warming, the RBF returned to baseline in the artery and vein. Three and 6
      minutes after warming, the mean +/- SE CBF significantly decreased 16.6% +/- 4.2%
      and 24.2% +/- 4.7%, respectively (P = .001 for both). Nine minutes after warming,
      the measurements returned to baseline. CONCLUSIONS: The RBF increased and the CBF
      decreased in the foveal region after cessation of ocular warming in healthy young
      volunteers. The CBF in the foveal region may contribute to maintaining a constant
      retinal temperature in response to ocular warming.

PMID- 15477460
TI  - Effect of low-dose latrunculin B on anterior segment physiologic features in the
      monkey eye.
AB  - OBJECTIVES: To determine if low doses of topical latrunculin B (LAT-B) will
      increase outflow facility and decrease intraocular pressure without damaging the
      cornea and if they will inhibit miotic and accommodative responses to pilocarpine
      in monkeys. METHODS: We measured intraocular pressure (Goldmann tonometry) before
      and after 1 and 9 doses of 0.005% and 0.01% topical LAT-B and vehicle given twice
      daily on successive weeks; outflow facility (perfusion) following 15 doses;
      central corneal thickness (ultrasonic pachymetry) before and after 1 and 9 doses
      of 0.01% LAT-B and vehicle; pupillary diameter (calipers); and accommodation
      (refractometry) before and after 1 dose of 0.005% and 0.02% LAT-B. RESULTS:
      Latrunculin-B dose-dependently decreased intraocular pressure, multiple doses
      more than a single dose. Maximal mean +/- SEM hypotension after 1 dose was 2.5 +/
      0.3 mm Hg (0.005% LAT-B; n = 8; P<.001) or 2.7 +/- 0.6 mm Hg (0.01% LAT-B; n =
      8; P<.005); maximal mean +/- SEM hypotension after 9 doses was 3.2 +/- 0.5 mm Hg
      (0.005% LAT-B; n = 8; P<.001) or 4.4 +/- 0.6 mm Hg (0.01% LAT-B; n = 8; P<.001).
      Outflow facility was increased by mean +/- SEM 75% +/- 13% (n = 7; P<.005).
      Central corneal thickness was not changed after 1 or 9 doses of 0.01% LAT-B.
      Miotic and accommodative responses to intramuscular pilocarpine were dose
      dependently inhibited. With 0.02% LAT-B, inhibition of miosis was substantial,
      whereas the inhibition of accommodation was only about 25%. With 0.005% LAT-B,
      the effects were trivial. CONCLUSIONS: In ocular normotensive monkeys, 0.005% and
      0.01% LAT-B administered topically increases outflow facility and/or decreases
      intraocular pressure without corneal effects. Multiple doses reduce intraocular
      pressure more than a single dose. Latrunculin-B dose-dependently relaxes the iris
      sphincter and ciliary muscle, with some separation of miotic and accommodative
      effects. Clinical Relevance Multiple treatments with low topical doses of LAT-B
      may substantially reduce outflow resistance in eyes with glaucoma without
      adversely affecting the cornea.

PMID- 15477461
TI  - Steroid-induced ocular hypertension in normal cattle.
AB  - OBJECTIVES: To determine whether the bovine eye develops elevation of intraocular
      pressure (IOP) in response to topical corticosteroid use and to develop a
      reliable model of steroid-induced elevation of IOP in an animal. METHODS:
      Intraocular pressure was monitored by Perkins applanation tonometry in a group of
      12 cows receiving topically administered prednisolone acetate in 1 eye 3 times a
      day for a period of 49 days after the establishment of baseline IOP values.
      Perkins readings were converted to IOP in mm Hg using calibration curves derived
      from in vitro cannulation manometric experiments and validated with in vivo
      manometric measurements. Intraocular pressure was also monitored for 50 days
      after the discontinuation of corticosteroid therapy. RESULTS: Intraocular
      pressure began to increase after 3 weeks of treatment in 100% of the cow eyes
      receiving corticosteroid and reached a peak 1 week later. Peak interocular IOP
      differences between the corticosteroid-treated eye and the fellow control eye
      reached up to 15 mm Hg and began to decline after the discontinuation of
      treatment but remained significantly elevated for a period of 3 more weeks.
      CONCLUSIONS: Bovine eyes exhibit a robust steroid-induced ocular hypertensive
      response, with 100% occurrence in this trial. The IOP elevation caused by
      corticosteroid slowly subsides after discontinuation of treatment. Clinical
      Relevance The mechanisms of steroid-induced glaucoma may be related to those
      involved in primary open-angle glaucoma and could provide the clues to elucidate
      the pathogenesis of the latter. The high prevalence of corticosteroid-induced
      elevation of IOP in the cow and the large amount of tissue available will permit
      studies on the mechanism of this phenomenon not previously possible.

PMID- 15477462
TI  - Intravitreally injected human immunoglobulin attenuates the effects of
      Staphylococcus aureus culture supernatant in a rabbit model of toxin-mediated
      endophthalmitis.
AB  - OBJECTIVE: To determine whether human immunoglobulin attenuates the toxic effects
      of Staphylococcus aureus culture supernatant in a rabbit model of
      endophthalmitis. METHODS: Immunoglobulin binding to products of S aureus strain
      RN4220 was tested by Western blot analysis using known toxins (beta-hemolysin and
      toxic shock syndrome toxin-1) and a concentrated culture supernatant containing S
      aureus exotoxins (pooled toxin). To induce endophthalmitis, pooled toxin was
      injected into the rabbit vitreous. For immunoglobulin treatment, immunoglobulin
      and pooled toxin were either mixed and injected simultaneously or immunoglobulin
      was injected immediately after or 6 hours after pooled toxin injection. Severity
      of endophthalmitis was graded according to a 9-day course with clinical
      examination (slitlamp biomicroscopy or indirect ophthalmoscopy) and evaluation of
      histologic sections. RESULTS: The toxic effects of pooled toxin were markedly
      reduced when immunoglobulin was mixed with pooled toxin and injected
      simultaneously. Delayed injection of immunoglobulin diminished its ability to
      reduce toxicity. Clinical and histologic signs of toxicity were partially
      attenuated when immunoglobulin was injected immediately after pooled toxin, but
      only minimal clinically detectable reductions in toxicity were observed when
      immunoglobulin injection was delayed for 6 hours. CONCLUSION: Pooled human
      immunoglobulin can attenuate the toxic intravitreal effects of a concentrated
      culture supernatant containing S aureus exotoxins. Clinical Relevance
      Immunoglobulin may represent a novel adjuvant in the treatment of bacterial
      endophthalmitis. To optimize the potential therapeutic benefit, maximizing the
      mixture of immunoglobulin with bacterial products and early intervention are
      likely to be important.

PMID- 15477463
TI  - Histological effect and protein expression in subthreshold transpupillary
      thermotherapy in rabbit eyes.
AB  - OBJECTIVE: To investigate the histological effect of subthreshold transpupillary
      thermotherapy (TTT) on the retina. METHODS: We performed TTT in normal pigmented
      rabbit eyes using an 810-nm diode laser with spot size of 1.2 mm, power of 50 mW,
      and varying durations of 15, 30, or 60 seconds. Four weeks later, fluorescein
      angiography was performed, and the enucleated eyes were examined by means of
      electron microscopy and immunohistochemical staining. RESULTS: Funduscopy
      immediately and at 4 weeks showed no discernable changes at TTT sites, and
      fluorescein angiography at 4 weeks showed no abnormalities. However, electron
      microscopy showed photoreceptor and retinal pigment epithelium cell disruption,
      changes more prominent with longer durations of treatment. Immunohistochemical
      staining was positive for heat shock protein 60, heat shock protein 70, tumor
      necrosis factor alpha, and vascular cell adhesion molecule 1 in the
      photoreceptors and retinal pigment epithelium at TTT sites. Untreated control
      eyes showed no staining. CONCLUSIONS: Despite the absence of changes evident by
      funduscopy and fluorescein angiography, TTT resulted in dose-dependent
      histological changes in photoreceptors and retinal pigment epithelium. The
      induction of heat shock proteins, cytokines, and cell adhesion molecules may play
      a role in the tissue response to subthreshold TTT. Clinical Relevance
      Unrecognized damage to the retina and retinal pigment epithelium may contribute
      to visual loss in eyes that undergo subthreshold TTT.

PMID- 15477464
TI  - Chronic ischemia induces regional axonal damage in experimental primate optic
      neuropathy.
AB  - OBJECTIVES: To evaluate the effects of chronic optic nerve ischemia in a nonhuman
      primate model and to evaluate the regional variability of axonal loss. METHODS:
      Unilateral ischemic optic neuropathy was induced by administration of endothelin
      1 to the retrobulbar space via osmotic pumps in 12 primates for 6 to 12 months.
      The transversely cut sections were stained and divided into 16 regions. Average
      axonal density in each region was quantified and compared with the untreated
      contralateral control eyes. RESULTS: Mean axonal density was 208 310/mm(2) and
      220 661/mm(2) in treated and control eyes, respectively (P = .03, 1-tailed paired
      t test), for the entire group. Two-way analysis of variance showed a significant
      effect of endothelin-1 on overall axonal density for the experimental group
      (P<.001). Among the nerves with significant axonal loss, the mean axonal loss was
      11.6% (4%-21%). Regional mapping of the damage showed the axonal loss varied in
      the damaged nerves; the damaged regions often clustered within specific
      quadrants. CONCLUSION: Chronic ischemia induced by local administration of
      endothelin-1 causes significant loss of optic nerve axons with varying regional
      susceptibility. Clinical Relevance Localized damage occurs in other types of
      optic neuropathy, such as glaucoma, and may result from regional differences in
      anatomy, metabolism, or vasculature of the primate optic nerve.

PMID- 15477465
TI  - Axenfeld-Rieger anomaly: a novel mutation in the forkhead box C1 (FOXC1) gene in
      a 4-generation family.
AB  - OBJECTIVE: To characterize DNA mutations in a pedigree of Axenfeld-Rieger anomaly
      (ARA) (Online Mendelian Inheritance of Man 601631), a clinically and genetically
      heterogeneous, autosomal dominantly inherited disorder associated with anterior
      chamber abnormalities and glaucoma. DESIGN: Observational case-control and DNA
      linkage and screening studies. PARTICIPANTS: Affected (10 cases) and unaffected
      (5 controls) members of a family with ARA. METHODS: Clinical characteristics of
      ARA were documented by history or physical examination of symptomatic
      individuals. With their informed consent, a blood sample was collected from each
      of 10 affected and 5 unaffected family members. DNA was tested for linkage to the
      IRID1 locus at chromosome 6p25, a known locus for ARA/Rieger syndrome. A
      candidate gene previously mapped at this locus, FOXC1, was screened for mutations
      in cases and controls. Main Outcome Measure Linkage of the ARA phenotype at the
      6p25 locus and mutation detected in FOXC1. RESULTS: Direct sequencing of FOXC1
      detected a new mutation, T272C, that segregated with the ARA phenotype in this
      family and was not detected in DNA from family members without ARA. This
      mutation, a T-->C transition, is predicted to result in a change of isoleucine to
      threonine (Ile9lThr) in a highly conserved location within the first helix of the
      forkhead domain. CONCLUSION: Characterization of the FOXC1 mutation in family
      members with ARA furthers our understanding of the molecular origin of
      developmental glaucoma and other anterior segment disorders.

PMID- 15477466
TI  - The Pan American Association of Ophthalmology.

PMID- 15477467
TI  - Paraffin embedding technique for specimens obtained by vitrectomy.

PMID- 15477468
TI  - Pleomorphic adenoma of the lacrimal gland in a child after treatment of acute
      lymphoblastic leukemia.

PMID- 15477469
TI  - Reversible changes in frequency-doubling perimetry with transiently elevated
      intraocular pressure.

PMID- 15477470
TI  - Acetazolamide-induced thrombocytopenia.

PMID- 15477471
TI  - Choroidal neovascularization after globe penetration by peribulbar anesthesia.

PMID- 15477472
TI  - Acute severe vision decrease immediately after photodynamic therapy.

PMID- 15477473
TI  - Using 18F-fluoro-2-deoxyglucose positron emission tomography to detect primary
      lung cancer in an isolated choroidal metastasis.

PMID- 15477474
TI  - Ocular hypotony secondary to spontaneously ruptured sclera in choroidal coloboma.

PMID- 15477475
TI  - Juvenile xanthogranuloma with presumed involvement of the optic disc and retina.

PMID- 15477476
TI  - Bilateral optic neuropathy associated with voluntary globe luxation and floppy
      eyelid syndrome.

PMID- 15477477
TI  - Imitation of typical birdcall causes ocular perforation by a tawny owl attack.

PMID- 15477478
TI  - Circumferential peripheral retinal cavernous hemangioma.

PMID- 15477479
TI  - Symblepharon as the only external sign of an occult intraocular foreign body.

PMID- 15477480
TI  - Visualization of the Cloquet canal during triamcinolone-assisted vitrectomy.

PMID- 15477481
TI  - Five-year evolution of basal laminar drusen combined with vitelliform macular
      detachment.

PMID- 15477482
TI  - Sympathetic ophthalmia and indocyanine green angiography.

PMID- 15477483
TI  - Regarding chemoreduction for retinoblastoma and intracranial neoplasms.

PMID- 15477484
TI  - Rinsing of the cannula prior to intravitreal injection.

PMID- 15477486
TI  - Radial optic neurotomy for nonischemic central retinal vein occlusion.

PMID- 15477488
TI  - The question of radial optic neurotomy in central retinal vein occlusion.

PMID- 15477490
TI  - Adverse ocular effects from lice shampoo.

PMID- 15477491
TI  - GenomeMixer: a complex genetic cross simulator.
AB  - GenomeMixer is a cross-platform application that simulates meiotic recombination
      events for large and complex multigenerational genetic crosses among sexually
      reproducing diploid species and outputs simulated progeny to several standard
      mapping programs. AVAILABILITY: Documentation, C++ source, and binaries for Mac
      OS X and x86 Linux are freely available at http://www.nervenet.org/genome_mixer/.
      GenomeMixer can be compiled on any system with support for the Trolltech Qt
      toolkit, including Windows.

PMID- 15477492
TI  - Recurrent tuberculosis in the United States and Canada: relapse or reinfection?
AB  - Recurrence of active tuberculosis after treatment can be due to relapse of
      infection with the same strain or reinfection with a new strain of Mycobacterium
      tuberculosis. The proportion of recurrent tuberculosis cases caused by
      reinfection has varied widely in previous studies. We evaluated cases of
      recurrent tuberculosis in two prospective clinical trials: a randomized study of
      two regimens for the last 4 months of treatment (n = 1,075) and a study of a
      twice-weekly rifabutin-containing regimen for human immunodeficiency virus
      infected tuberculosis (n = 169). Isolates at diagnosis and from positive cultures
      after treatment completion underwent genotyping using IS6110 (with secondary
      genotyping for isolates with less than six copies of IS6110). Of 85 patients
      having a positive culture after completing treatment, 6 (7.1%) were classified as
      false-positive cultures by a review committee blinded to treatment assignment. Of
      the remaining 75 cases with recurrent tuberculosis and genotyping data available,
      72 (96%; 95% confidence interval, 88.8-99.2%) paired isolates had the same
      genotype; only 3 (4%; 95% confidence interval, 0.8-11.2%) had a different
      genotype and were categorized as reinfection. We conclude that recurrent
      tuberculosis in the United States and Canada, countries with low rates of
      tuberculosis, is rarely due to reinfection with a new strain of M. tuberculosis.

PMID- 15477493
TI  - Interleukin-17F induces pulmonary neutrophilia and amplifies antigen-induced
      allergic response.
AB  - Interleukin (IL)-17F is a recently described human cytokine belonging to the IL
      17 gene family, but its in vivo function remains to be determined. To this end, a
      full-length mouse IL-17F cDNA sequence with a 483-bp coding region sequence was
      first identified. Pulmonary gene transfer of an IL-17F expression construct
      (pcDNAmIL-17F) in mice was used to investigate its regulatory role. The results
      showed first that a significant increase in the number of neutrophils was seen in
      the bronchoalveolar lavage fluids of IL-17F-transduced mice, concomitant with
      increased expression of genes encoding C-X-C chemokines and inflammatory
      cytokines when compared with mock and phosphate-buffered saline control animals.
      Mucosal transfer of the IL-17F gene in ovalbumin (OVA)-sensitized mice before
      antigen (Ag) challenge enhanced the levels of Ag-induced pulmonary neutrophilia,
      but not eosinophilia, goblet cell hyperplasia, and mucin gene expression.
      However, no significant change in the levels of Th2 cytokine expression was
      noted. A significant enhancement of ventilatory timing in response to inhaled
      methacholine was also seen in IL-17F-transduced, Ag-sensitized mice, whereas a
      small but significant increase was found in IL-17F-transduced, naive mice. These
      results suggest a role for IL-17F in the induction of neutrophilia in the lungs
      and in the exacerbation of Ag-induced pulmonary inflammation.

PMID- 15477494
TI  - Small airway morphometry and improvement in pulmonary function after lung volume
      reduction surgery.
AB  - We examined small airway morphometry from resected lung specimens in 25 patients
      with severe emphysema undergoing lung volume reduction surgery (LVRS) and
      correlated their pathologic findings to changes in FEV(1) 6 months after LVRS.
      Patients were classified into two groups: responders had a more than 12% and a
      more than 200-ml change in FEV(1) at 6 months, and nonresponders had 12% or less
      and/or 200 ml or less change in FEV(1). Epithelial height (EH) and perimeters and
      areas of peribronchial smooth muscle, epithelium, and subepithelial space were
      measured quantitatively. The degrees of interstitial fibrosis, vascular
      sclerosis, goblet cell hyperplasia, squamous metaplasia, chronic inflammation,
      peribronchial fibrosis, and bullous disease were assessed semiquantitatively.
      Despite similar baseline characteristics, nonresponders had a greater EH (0.045
      vs. 0.035 mm, p = 0.025), greater EH adjusted for basement membrane perimeter
      (0.040 vs. 0.011, p = 0.016), greater epithelial area adjusted for basement
      membrane area (0.561 vs. 0.499, p = 0.040), and less bullous disease (1.7 vs.
      2.6, p = 0.011) compared with responders. We found a linear relationship between
      percentage change in FEV(1) and bullous disease and inverse relationships between
      percentage change in FEV(1) and interstitial fibrosis, goblet cell hyperplasia,
      peribronchial fibrosis, and vascular sclerosis. We conclude that small airway
      morphometry and lung histopathology in patients with severe emphysema have an
      important influence on changes in FEV(1) 6 months after LVRS.

PMID- 15477495
TI  - A novel role for tachykinin neurokinin-3 receptors in regulation of human
      bronchial Ganglia neurons.
AB  - The neuropeptide tachykinins and their receptors have been implicated in the
      pathogenesis of lung disease, although the role of the tachykinin neurokinin-3
      receptor has not been elucidated. Using confocal microscopy, we identified
      tachykinin neurokinin-3 receptors on human bronchial parasympathetic ganglion
      neurons. Electrophysiologic recordings demonstrated that activation of sensory
      nerve fibers, either by antidromic stimulation or capsaicin, depolarized these
      neurons. This response was mimicked by exogenously applied tachykinin neurokinin
      3 receptor-selective agonist, senktide analogue, but not significantly by
      tachykinin neurokinin-1 or neurokinin-2 receptor-selective agonists. Responses to
      endogenous tachykinins or exogenous selective tachykinin neurokinin-3 receptor
      activation with senktide analogue were inhibited by the selective tachykinin
      neurokinin-3 receptor antagonists, SB 223412 or SB 235375. We provide the first
      evidence that tachykinin neurokinin-3 receptors regulate human bronchial
      parasympathetic ganglion neurotransmission by activation of a peripheral reflex.
      This pathway may play a significant role in controlling bronchomotor tone and air
      flow to the lung.

PMID- 15477497
TI  - Low exhaled nitric oxide in school-age children with bronchopulmonary dysplasia
      and airflow limitation.
AB  - Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, may be
      associated with long-term airflow limitation. Survivors of BPD may develop asthma
      like symptoms in childhood, with a variable response to beta(2)-agonists.
      However, the pathologic pathways underlying these respiratory manifestations are
      still unknown. The aim of this study was to measure exhaled nitric oxide (FE(NO))
      and lung function in a group of 31 school-age survivors of BPD. They showed
      variable degrees of airflow obstruction (mean FEV(1) 77.8 +/- 2.3% predicted)
      unresponsive to beta(2)-agonists in 72% of the subjects. Their FE(NO) values
      (geometric mean [95% confidence interval]: 7.7 [+/- 1.1] ppb) were significantly
      lower than in a group of healthy matched control subjects born at term (10.7 [+/-
      1.1] ppb, p < 0.05) and a group of preterm children without BPD (9.9 [+/- 1.1]
      ppb, p < 0.05). The children with BPD were also compared with a group of 31
      patients with asthma with a comparable airflow limitation (FEV(1) 80.2 +/- 2.1%
      predicted) and showed FE(NO) values four times lower than in those with asthma
      (24.9 [+/- 1.2] ppb, p < 0.001). In conclusion, unlike children with asthma,
      school-age survivors of BPD have airflow limitation associated with low FE(NO)
      values and lack of reversibility to beta(2)-agonists, probably as a result of
      mechanisms related to early life structural changes in the airways.

PMID- 15477496
TI  - Neuropathology in rhinosinusitis.
AB  - Pathophysiologic differences in neural responses to hypertonic saline (HTS) were
      investigated in subjects with acute sinusitis (n = 25), subjects with chronic
      fatigue syndrome (CFS) with nonallergic rhinitis (n = 14), subjects with active
      allergic rhinitis (AR; n = 17), and normal (n = 20) subjects. Increasing
      strengths of HTS were sprayed into their nostrils at 5-minute intervals.
      Sensations of nasal pain, blockage, and drip increased with concentration and
      were significantly elevated above normal. These parallels suggested activation of
      similar subsets of afferent neurons. Urea and lysozyme secretion were dose
      dependent in all groups, suggesting that serous cell exocytosis was one source of
      urea after neural stimulation. Only AR and normal groups had mucin dose responses
      and correlations between symptoms and lysozyme secretion (R(2) = 0.12-0.23). The
      lysozyme dose responses may represent axon responses in these groups. The
      neurogenic stimulus did not alter albumin (vascular) exudation in any group.
      Albumin and mucin concentrations were correlated in sinusitis, suggesting that
      nonneurogenic factors predominated in sinusitis mucous hypersecretion. CFS had
      neural hypersensitivity (pain) but reduced serous cell secretion. HTS nasal
      provocations identified significant, unique patterns of neural and mucosal
      dysregulation in each rhinosinusitis syndrome.

PMID- 15477498
TI  - Synergistic production of lung free radicals by diesel exhaust particles and
      endotoxin.
AB  - The present study tested the hypothesis that free radicals were involved in the
      pathogenesis of lung injury caused by diesel exhaust particles (DEP) and
      bacterial lipopolysaccharides (LPS). Intratracheal coinstillation of DEP and LPS
      in rat lungs resulted in synergistic enhancement of free radical generation in
      the lungs. The radical metabolites were characterized as lipid-derived by
      electron spin resonance (ESR). The free radical generation was paralleled by a
      synergistic increase in total protein and by infiltration of neutrophils in the
      bronchoalveolar lavage (BAL) fluid of the lungs. Experiments with NADP-reduced
      (NADPH) oxidase and iNOS knockout mice showed that NADPH oxidase and iNOS did not
      contribute to free radical generation. However, pretreatment with the macrophage
      toxicant GdCl(3), the xanthine oxidase (XO) inhibitor allopurinol, and the
      Fe(III) chelator Desferal resulted in a marked decrease in free radical
      generation, lung inflammation, and lung injury. These effects were concomitant
      with the inhibition of XO activity in BAL, suggesting that the activated
      macrophages and the activity of XO contributed to the generation of free radicals
      caused by DEP and LPS. This is the first demonstration that DEP and LPS work
      synergistically to enhance free radical generation in lungs, mediated by the
      activation of local XO.

PMID- 15477499
TI  - Hypercapnia via reduced rate and tidal volume contributes to lipopolysaccharide
      induced lung injury.
AB  - Appreciating that CO2 modifies the chemical reactivity of nitric oxide (NO)
      derived inflammatory oxidants, we investigated whether hypercapnia would modulate
      pulmonary inflammatory responses. Rabbits (n = 72) were ventilated with
      approximately 7-ml/kg tidal volume for 6 hours. Animals were randomized to one of
      the following conditions: eucapnia (Pa(CO2) at approximately 35-40 mm Hg),
      eucapnia + lipopolysaccharide (LPS), eucapnia + LPS + inhaled NO (iNO delivered
      at approximately 20 ppm), hypercapnia (Pa(CO2) at approximately 60 mm Hg),
      hypercapnia + LPS, and hypercapnia + LPS + iNO. The hypercapnia + LPS groups
      compared with groups exposed to eucapnia + LPS displayed significantly increased
      bronchoalveolar lavage fluid protein concentrations (p < 0.05), lung wet-to-dry
      ratios (p < 0.05), bronchoalveolar lavage fluid cell counts (p < 0.05), and lung
      histologic alterations consistent with greater injury. Furthermore, expression of
      inducible nitric oxide synthase (p < 0.05), tissue myeloperoxidase content (p <
      0.05), and formation of lung protein 3-nitrotyrosine derivatives (p < 0.05) was
      greatest under conditions of hypercapnia + LPS. Groups exposed to hypercapnic
      conditions without LPS did not manifest these changes. The inhalation of iNO
      attenuated selected indices of lung injury. We conclude that hypercapnia induced
      by means of reduced rate and tidal volume amplifies pulmonary inflammatory
      responses.

PMID- 15477500
TI  - Viral pathogens in multiple sclerosis: an intriguing (hi)story.

PMID- 15477501
TI  - Age-associated white matter lesions and dementia: are these lesions causal or
      casual?

PMID- 15477502
TI  - Syphilis and human immunodeficiency virus: prevention and politics.

PMID- 15477503
TI  - Emerging antimicrobial-resistant infections.

PMID- 15477504
TI  - Intravenous immunoglobulin treatment following the first demyelinating event
      suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled
      trial.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIg) has been reported to reduce disease
      activity in patients with relapsing-remitting multiple sclerosis. We assessed the
      effect of IVIg treatment in patients after the first neurological event
      suggestive of demyelinative disease and evaluated the occurrence of a second
      attack and dissemination in time demonstrated by brain magnetic resonance imaging
      within the first year from onset. METHODS: We conducted a randomized, placebo
      controlled, double-blind study in 91 eligible patients enrolled within the first
      6 weeks of neurological symptoms. Patients were randomly assigned to receive IVIg
      treatment (2-g/kg loading dose) or placebo, with boosters (0.4 g/kg) given once
      every 6 weeks for 1 year. Neurological and clinical assessments were done every 3
      months, and brain magnetic resonance imaging was performed at baseline and the
      end of the study. RESULTS: The cumulative probability of developing clinically
      definite multiple sclerosis was significantly lower in the IVIg treatment group
      compared with the placebo group (rate ratio, 0.36 [95% confidence interval, 0.15
      0.88]; P = .03). Patients in the IVIg treatment group had a significant reduction
      in the volume and number of T2-weighted lesions and in the volume of gadolinium
      enhancing lesions as compared with the placebo group (P = .01, P = .01, and P =
      .03, respectively). Treatment was well tolerated, compliance was high, and
      incidence of adverse effects did not differ significantly between groups.
      CONCLUSIONS: Intravenous immunoglobulin treatment for the first year from onset
      of the first neurological event suggestive of demyelinative disease significantly
      lowers the incidence of a second attack and reduces disease activity as measured
      by brain magnetic resonance imaging.

PMID- 15477505
TI  - Relapsing-remitting multiple sclerosis and human herpesvirus 6 active infection.
AB  - BACKGROUND: Recent studies have focused on the relationship between human
      herpesvirus 6 (HHV-6) and multiple sclerosis (MS). OBJECTIVE: To analyze HHV-6
      messenger RNA expression in patients with relapsing-remitting (RR) MS vs healthy
      blood donors (HBDs). DESIGN: One hundred fifty-four subjects were enrolled in the
      study: 105 patients with RRMS (32 in relapse) and 49 HBDs. Total DNA and
      messenger RNA were extracted from serum and blood samples, respectively, and
      analyzed by quantitative real-time reverse transcription-polymerase chain
      reaction for the detection of 3 HHV-6 immediate-early genes (U16/U17,U89/U90, and
      U94) and both HHV-6 variants (HHV-6A and HHV-6B). RESULTS: Active HHV-6 infection
      was detected in 16% of patients with RRMS vs 0% of HBDs (P = .003). Seven
      patients with RRMS with exacerbation had HHV-6 active replication, and the virus
      remained latent in only 1 of them. We did not find any statistically significant
      difference between HHV-6 active or latent infection for patients in remission (P
      = .12). Among patients with RRMS with HHV-6 active replication, viral load was
      higher when they experienced an acute attack than when in remission (P = .04). In
      those patients with RRMS who had an active infection only, HHV-6A was found. Cell
      free HHV-6 DNA detected in serum samples confirmed the results. CONCLUSIONS: The
      results show that a subset of patients with RRMS experience HHV-6 active
      infection, and there likely is an association between the viral active
      replication and relapses; therefore, HHV-6 active infection may imply a greater
      risk of exacerbations in a subgroup of patients with RRMS.

PMID- 15477506
TI  - Cerebral white matter lesions and the risk of dementia.
AB  - OBJECTIVE: To study the association between white matter lesions (WML) in
      specific locations and the risk of dementia. DESIGN: The Rotterdam Scan Study, a
      prospective population-based cohort study. We scored periventricular and
      subcortical WML on magnetic resonance imaging and observed participants until
      January 2002 for incident dementia. SETTING: General population. PARTICIPANTS: We
      included 1077 people aged 60 to 90 years who did not have dementia at baseline.
      MAIN OUTCOME MEASURE: Incident dementia by Diagnostic and Statistical Manual of
      Mental Disorders, Third Edition (DSM III-R) criteria. RESULTS: During a mean
      follow-up of 5.2 years, 45 participants developed dementia. Higher severity of
      periventricular WML increased the risk of dementia, whereas the association
      between subcortical WML and dementia was less prominent. The adjusted hazard
      ratio of dementia for each standard deviation increase in periventricular WML
      severity was 1.67 (95% confidence interval, 1.25-2.24). This increased risk was
      independent of other risk factors for dementia and partly independent of other
      structural brain changes on magnetic resonance imaging. CONCLUSION: White matter
      lesions, especially in the periventricular region, increase the risk of dementia
      in elderly people.

PMID- 15477507
TI  - Long-term brain magnetic resonance imaging changes after optic neuritis in
      patients without clinically definite multiple sclerosis.
AB  - BACKGROUND: Long-term follow-up of the Optic Neuritis Treatment Trial (ONTT)
      cohort to evaluate brain magnetic resonance imaging (MRI) in patients who have
      not developed clinically definite multiple sclerosis. OBJECTIVE: To determine the
      proportion of patients with monosymptomatic optic neuritis who manifest new brain
      MRI lesions without having developed clinically definite multiple sclerosis 10 to
      14 years after enrollment in the ONTT. DESIGN: Observational study. SETTING:
      Fourteen clinical centers. PARTICIPANTS: One hundred eight ONTT patients who had
      not developed clinically definite multiple sclerosis 10 to 14 years after study
      enrollment. MAIN OUTCOME MEASURE: Development of new T2 lesions on follow-up
      brain MRI. RESULTS: At least 1 T2 lesion 3 mm or larger was observed on follow-up
      MRIs in 27 (44%) of 61 patients with normal baseline MRIs. Additional lesions (>
      or =3 mm) were present on follow-up MRIs in 26 (74%) of 35 patients with abnormal
      baseline MRIs. CONCLUSIONS: A subset of patients with monosymptomatic optic
      neuritis manifest neither clinical signs nor MRI evidence of demyelination after
      more than 10 years of follow-up. In other cases followed up for this length of
      time, MRI signal abnormalities may accumulate without causing new clinical
      manifestations of multiple sclerosis. This information is useful in counseling
      patients who develop first-episode optic neuritis.

PMID- 15477508
TI  - Effects of white matter lesions and lacunes on cortical function.
AB  - BACKGROUND: Subcortical ischemic vascular dementia has been ascribed to prominent
      frontal lobe dysfunction secondary to ischemic lesions in frontothalamic
      circuits. Whether small-vessel disease in fact predominantly affects the frontal
      lobes is not well documented. OBJECTIVE: To investigate the effects of
      subcortical lesions (lacunes and white matter lesions [WML]) on cortical
      function, as reflected in glucose metabolism and cognitive function, in elderly
      individuals. DESIGN: Cross-sectional analyses of case series. SETTING:
      Multicenter, university-based study of subcortical vascular dementia. PATIENTS:
      Persons with normal cognition, mild cognitive impairment, or dementia and with
      and without lacunes on magnetic resonance images. MAIN OUTCOME MEASURES: Regional
      cerebral glucose metabolism, normalized regional metabolic activity, and
      neuropsychological test scores. Major hypotheses were that volume of lacunes and
      WML correlate selectively with hypometabolism of prefrontal cortex and failure of
      executive cognitive ability. RESULTS: Lacunes correlated with metabolic rates in
      dorsolateral frontal cortex (DLF); WML substantially reduced metabolic rates
      throughout cortex, most strongly so in DLF. When regional metabolic activity was
      normalized to whole brain activity, lacunes remained correlated with DLF
      activity, whereas the WML effect was no longer found, probably because of its
      general distribution. Regional cerebral glucose metabolism and normalized
      activity in DLF also correlated with cortical atrophy. Metabolic activity in DLF
      correlated with executive function, memory, and global cognitive function, while
      activity in middle temporal gyrus correlated with memory and global function but
      not executive function. CONCLUSIONS: The metabolic effects of lacunes and WML are
      most apparent in DLF, but the effects of WML are generalized and frontal
      hypometabolism correlates with memory and global impairment, cognitive as well as
      executive function. The effects of subcortical cerebrovascular disease appear to
      converge on the frontal lobes but are diffuse, complex, and of modest magnitude.

PMID- 15477509
TI  - Recurrent lymphocytic meningitis: the role of herpesviruses.
AB  - BACKGROUND: Herpes simplex virus 2 (HSV-2) and HSV-1 have been recognized as
      causes of recurrent aseptic lymphocytic meningitis (RALM). However, the role of
      other herpesviruses has not been systematically assessed. OBJECTIVES: To evaluate
      the cause of RALM by using polymerase chain reaction (PCR) tests detecting
      varicella-zoster virus (VZV), cytomegalovirus (CMV), or human herpesvirus 6 (HHV
      6), in addition to HSV, on cerebrospinal fluid (CSF) samples; and to assess the
      utility of PCR and antibody analyses in consecutive episodes of RALM. DESIGN: The
      PCR and antibody results for herpesviruses were analyzed from 14 patients having
      48 episodes of RALM. RESULTS: The CSF PCR results for VZV, CMV, and HHV-6 were
      negative in 12, 10, and 11 patients investigated, respectively, and antibodies
      against VZV, CMV, and HHV-6 showed only old immunity. Herpes simplex virus 2 was
      detected from the CSF in 10 patients, and HSV-1 in 1 patient. In 6 of these 11
      patients, the HSV PCR result was positive in more than one disease episode. A
      significant increase of serum antibodies for HSV was seen in only 1 of 15
      episodes examined. An intrathecal antibody response to HSV was not recognized in
      9 episodes investigated in these 11 patients. CONCLUSIONS: We could not find
      evidence of VZV, CMV, or HHV-6 in the pathogenesis of RALM, although most
      patients were previously infected by those viruses. Herpes simplex virus 2 was
      detected from the CSF in most patients, and often repeatedly, which further
      confirms the role of this virus in RALM. The causative diagnosis was obtained
      only by PCR, whereas antibody analysis was not clinically useful.

PMID- 15477510
TI  - Double-blind, placebo-controlled study of entacapone in levodopa-treated patients
      with stable Parkinson disease.
AB  - BACKGROUND: The catechol O-methyltransferase inhibitor entacapone acts by
      extending the elimination half-life of levodopa and is currently approved as an
      adjunct to levodopa for the treatment of patients with Parkinson disease (PD)
      with motor fluctuations. OBJECTIVE: To determine if the addition of entacapone
      administration provides benefit to levodopa-treated PD patients who have a stable
      response to levodopa and do not experience motor complications. DESIGN:
      Prospective, double-blind, placebo-controlled trial. SETTING: Outpatient
      multicenter study. PATIENTS: Female and male patients 30 years or older with
      idiopathic PD receiving stable doses of levodopa or carbidopa with or without
      other dopaminergic therapies and who did not experience motor fluctuations were
      eligible for the study. MAIN OUTCOME MEASURES: Parkinsonian function and quality
      of life. RESULTS: The addition of entacapone did not improve motor scores on the
      Unified Parkinson's Disease Rating Scale in levodopa-treated PD patients who did
      not experience motor fluctuations. The mean +/- SE adjusted change between
      baseline and final treatment visit was -0.9 +/- 0.35 in the entacapone group and 
      0.8 +/- 0.35 in the placebo group (P = .83). Significant improvement with
      entacapone treatment was detected in several quality-of-life measures, including
      the Parkinson Disease Questionnaire 39, the 36-item Short-Form Health Survey, the
      Parkinson's Symptom Inventory, and investigator and subject Clinical Global
      Assessments. The drug was well tolerated by patients in this population.
      CONCLUSIONS: The catechol O-methyltransferase inhibitor entacapone, used as an
      adjunct to levodopa in PD patients who do not experience motor fluctuations, does
      not improve Unified Parkinson's Disease Rating Scale motor scores but does
      improve a variety of quality-of-life measures.

PMID- 15477511
TI  - Validity of family history data on primary adult-onset dystonia.
AB  - BACKGROUND: To our knowledge, no study has assessed the validity of family
      history data provided by probands with adult-onset dystonia. OBJECTIVE: To
      measure the sensitivity and specificity of interviewing patients with primary
      adult-onset dystonia as a method for obtaining information on dystonia in first
      degree relatives. PARTICIPANTS: Seventy probands with primary adult-onset
      dystonia were asked to identify first-degree relatives who had dystonia.
      Available relatives were then directly examined by a trained neurologist. The
      validity of the probands' reports was tested against the neurologists' diagnoses.
      RESULTS: Among 300 first-degree relatives who were examined, 26 received a
      diagnosis of dystonia. Only 7 of the 26 were identified by the probands' reports.
      Among the 274 relatives free of dystonia, the probands reported 5 as having
      dystonia. The probands' reports therefore yielded a sensitivity of 27.0% and a
      specificity of 98.2%. CONCLUSIONS: Because the family history method yields low
      sensitivity and incurs a risk of misclassification, it is of limited use in
      family studies of adult-onset dystonia. The only valid means of ascertaining
      dystonia among relatives remains neurological examination of at-risk subjects.

PMID- 15477512
TI  - Apolipoprotein E epsilon 4 is a determinant for Alzheimer-type pathologic
      features in tauopathies, synucleinopathies, and frontotemporal degeneration.
AB  - OBJECTIVES: To determine if apolipoprotein E epsilon 4 influences the frequency
      of Alzheimer-type pathologic features in tauopathies, synucleinopathies, and
      frontotemporal degeneration and to determine if the frequency of Alzheimer-type
      pathologic features in synucleinopathies is similar to the frequency of such
      features in tauopathies and frontotemporal degeneration. METHODS: A total of 285
      patients with pathologically proven neurodegenerative disorders, including
      diffuse and transitional Lewy body disease, frontotemporal degeneration,
      progressive supranuclear palsy, corticobasal degeneration, and multiple system
      atrophy, with a mean age of 75.1 +/- 9.3 years, were suitable for genetic and
      pathological analysis. Disorders were grouped as tauopathies (progressive
      supranuclear palsy and corticobasal degeneration), synucleinopathies (Lewy body
      disease and multiple system atrophy), and frontotemporal degeneration. Braak
      neurofibrillary tangle staging and quantitative scores of senile plaques were
      used to determine the degree of concomitant Alzheimer-type pathologic features in
      each case, and apolipoprotein E genotype was determined from DNA isolated from
      frozen brain tissue. The relationship of apolipoprotein E epsilon 4 to Alzheimer
      type pathologic features was determined. RESULTS: Across all neurodegenerative
      disorders, apolipoprotein E epsilon 4 and older age independently predicted the
      co-occurrence of Alzheimer-type pathologic features (P<.001), whereas female sex
      had a lesser effect (P = .03). When divided into the 3 subgroups (tauopathies,
      synucleinopathies, and frontotemporal degeneration), apolipoprotein E epsilon 4
      had a similar effect, whereas older age and female sex were less predictive.
      There was a significant difference between the frequency of Alzheimer-type
      pathologic features in synucleinopathies and the frequency of such features in
      tauopathies and frontotemporal degeneration (P<.001 for both). The frequency of
      apolipoprotein E epsilon 4 allele was not significantly different among the 3
      groups. CONCLUSIONS: Apolipoprotein E epsilon 4, independent of older age and
      sex, contributes to the co-occurrence of Alzheimer-type pathologic features in
      tauopathies, synucleinopathies, and frontotemporal degeneration, but this does
      not explain why Alzheimer-type pathologic features are significantly more likely
      to coexist with synucleinopathies than with either tauopathies or frontotemporal
      degeneration.

PMID- 15477513
TI  - Corticospinal physiology in patients with Prader-Willi syndrome: a transcranial
      magnetic stimulation study.
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is a genetic developmental disorder,
      mostly caused by a deletion on the paternal chromosome 15 or by a maternal
      uniparental disomy 15. Some PWS clinical and neurochemical features suggest an
      involvement of the corticospinal motor structures. OBJECTIVE: To explore the
      corticospinal physiology of PWS by transcranial magnetic stimulation. SETTING: A
      community-based hospital. METHODS: We studied motor evoked potentials in the
      first dorsal interosseous muscle of 21 young-adult patients with PWS. Thirteen
      patients had a deletion at chromosome 15; 8 had a uniparental disomy. We measured
      the following variables: relaxed motor threshold, central motor conduction time,
      duration of the central silent period, and short-interval intracortical
      inhibition and facilitation. We also recorded F waves in the first dorsal
      interosseous muscle. We had 11 normal controls. RESULTS: In the whole PWS group,
      motor threshold was higher as compared with controls (P<.05). The central motor
      conduction time, central silent period, and F waves were normal. Intracortical
      facilitation was reduced significantly (P<.001). Patients with PWS and a deletion
      had a weaker intracortical inhibition as compared with patients with PWS and a
      uniparental disomy (P<.05). CONCLUSIONS: Transcranial magnetic stimulation
      changes in patients with PWS suggested a hypo-excitability of the motor cortical
      areas. Defective neurogenesis of the cortical tissue and multiple transmitter
      alterations are the putative causes. Impaired intracortical inhibition might
      represent an electrical marker for a deletion defect.

PMID- 15477514
TI  - Is posttraumatic benign paroxysmal positional vertigo different from the
      idiopathic form?
AB  - BACKGROUND: Although head trauma is considered a common cause of benign
      paroxysmal positional vertigo (BPPV), clinical presentation and outcome of
      traumatic BPPV (t-BPPV) have not been systematically evaluated. OBJECTIVES: To
      compare the clinical presentation, patient's response to physical treatment, and
      outcome of patients with t-BPPV with those with the idiopathic form (i-BBPV).
      SETTING: Tertiary referral neuro-otology outpatient clinic. METHODS: We reviewed
      the clinical records of 247 consecutive patients with posterior canal BPPV during
      the years 1997 to 2000. All patients were diagnosed using the Dix-Hallpike test
      and treated using the particle repositioning maneuver. Patients with an onset of
      positional vertigo within 3 days of well-documented head trauma were included in
      the t-BPPV group. The outcome was compared with the outcome of 42 patients with i
      BPPV who were similarly treated and followed up. RESULTS: Twenty-one (8.5%) of
      the 247 patients with BPPV fulfilled the diagnostic criteria for t-BPPV. The most
      common cause of head trauma was motor vehicle crash, documented in 57% of the
      cases; half of the patients additionally suffered from a whiplash injury. While
      the other causes were diverse, common falls were predominant. Only 2 of the
      patients involved in motor vehicle crashes experienced brief loss of
      consciousness. Sixty-seven percent of patients with t-BPPV required repeated
      physical treatments for complete resolution of signs and symptoms in comparison
      to 14% of patients with i-BPPV (P<.001). During a mean +/-SD follow-up of 21.7 +/
      9.7 months, 57% of t-BPPV patients and 19% of i-BPPV controls had recurrent
      attacks (P<.004). CONCLUSIONS: The nature and severity of the traumas causing t
      BPPV are diverse, ranging from minor head injuries to more severe head and neck
      trauma with brief loss of consciousness. It appears that t-BPPV is more difficult
      to treat than i-BPPV, and also has a greater tendency to recur.

PMID- 15477515
TI  - Phenotypic features and genetic findings in 2 chinese families with Miyoshi
      distal myopathy.
AB  - BACKGROUND: Miyoshi distal myopathy (MM) and limb girdle muscular dystrophy type
      2B (LGMD2B) were found to map to the same mutant gene encoding for dysferlin on
      chromosome 2p13. Most reported cases were large inbred kindreds whose members
      demonstrated both MM and LGMD2B phenotypes. OBJECTIVE: To investigate the
      clinical, neurophysiological, histopathological, and genetic features in 4
      patients with MM from 2 unrelated Chinese families demonstrating linkage to the
      dysferlin locus. RESULTS: All patients were characterized by early adult onset,
      preferential atrophy, and weakness of calf muscles, marked elevation of serum
      creatine kinase levels, and absence of dysferlin staining. Magnetic resonance
      imaging showed fatty and fibrotic tissue signals in the affected muscles. Genetic
      analysis revealed novel compound heterozygous mutations, 1310+1G to A and GGG to
      GTC transition at nucleotide 1650 (G426V ) in one family and another novel
      compound heterozygous mutation, a deletion of C at nucleotide 477 and a CCG to
      CTG transition at nucleotide 6576 (P2068L), in the other family. CONCLUSION:
      Miyoshi distal myopathy in these 2 Chinese families demonstrated a homogenous
      phenotype and compound heterozygous mutations. Among the 4 mutations, 3 were
      novel mutations that, to our knowledge, have not been reported previously.

PMID- 15477516
TI  - Novel mutation in the SPG3A gene in an African American family with an early
      onset of hereditary spastic paraplegia.
AB  - BACKGROUND: Mutations in a novel GTPase gene SPG3A cause an autosomal dominant
      hereditary spastic paraplegia linked to chromosome 14q (SPG3), which accounts for
      approximately 10% to 15% of all autosomal dominant hereditary spastic paraplegia
      cases. The mutational spectrum of the SPG3A gene and the phenotype/genotype
      correlations have not yet been established. OBJECTIVE: To describe a kindred with
      an infantile onset of hereditary spastic paraplegia caused by a novel mutation in
      the SPG3A gene. PATIENTS: Complete neurological examination and genetic analysis
      were performed on 6 affected members of a small African American kindred. Linkage
      analysis to genetic markers near autosomal dominant hereditary spastic paraplegia
      loci on chromosomes 2p and 14q was performed. The coding sequence of the SPG3A
      gene was analyzed, and the identified change in the sequence was tested for being
      a benign polymorphism by sequencing 200 chromosomes from normal controls.
      RESULTS: Every affected individual had signs of uncomplicated spastic paraparesis
      without additional neurological abnormalities. None of the affected family
      members had ever walked normally. The history was consistent with an infantile
      onset, despite the normal acquisition of motor milestones. Genetic analysis
      suggested linkage to the SPG3A locus on chromosome 14q. Analysis of the SPG3A
      gene revealed a missense mutation C635T, predicted to result in a threonine to
      isoleucine substitution at codon 156. Analysis of 200 normal chromosomes did not
      identify the same change in healthy subjects. CONCLUSION: We report a novel
      mutation in the SPG3A gene in an African American family with an infantile onset
      of autosomal dominant hereditary spastic paraplegia.

PMID- 15477517
TI  - Levetiracetam induces a rapid and sustained reduction of generalized spike-wave
      and clinical absence.
AB  - BACKGROUND: Levetiracetam (LEV) is a new antiepileptic drug with efficacy in
      partial-onset seizures. We report a case in which generalized-onset absence
      seizures responded clinically and electrographically to LEV. METHODS: We
      evaluated with continuous video/electroencephalography an adult with generalized
      onset seizures given 3 antiepileptic drugs, 1 of which was LEV. Levetiracetam
      initiation 2 months before admission decreased patient-reported seizures.
      Interictal electroencephalography revealed generalized 3.5-Hz spike-wave and
      polyspike-wave discharges. Spike-wave bursts lasting 2 seconds or longer caused a
      pause in continuous reading aloud, consistent with clinical absence seizures.
      Levetiracetam was discontinued on admission, lamotrigine was gradually
      discontinued across 2 days, and topiramate was not changed. One encephalographer
      counted from video/electroencephalography recordings the number of spike-wave
      bursts in 1-hour time samples that included wake and sleep time. RESULTS: Spike
      wave bursts increased from 4 to 56 per hour at baseline (4000 mg of LEV per day)
      to 406 to 914 per hour less than 48 hours after LEV discontinuation.
      Levetiracetam treatment was restarted, and 3 hours after the first dose of 1000
      mg, spike-wave bursts dropped to 135 per hour. Response was sustained during the
      next 2 days. CONCLUSIONS: This case showed a dramatic, rapid effect of LEV
      discontinuation and reinstitution on generalized spike-wave burst frequency and
      clinical absence. The effects were independent of reduction of lamotrigine and
      without change in topiramate doses and occurred in a time course consistent with
      LEV pharmacokinetics. Levetiracetam may be effective in generalized-onset
      epilepsy, and randomized, controlled trials are indicated.

PMID- 15477518
TI  - A migrated acupuncture needle in the medulla oblongata.

PMID- 15477519
TI  - Lateral lower medullary infarction.

PMID- 15477520
TI  - Multiple sclerosis is not an autoimmune disease.

PMID- 15477521
TI  - Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease.

PMID- 15477522
TI  - Is multiple sclerosis an autoimmune disorder?

PMID- 15477523
TI  - Temporal arteritis. 1932.

PMID- 15477524
TI  - Spinocerebellar ataxia and peripheral neuropathy.

PMID- 15477525
TI  - Paroxysmal autonomic instability after brain injury.

PMID- 15477526
TI  - Epileptic nystagmus.

PMID- 15477527
TI  - Posterior cortical dementia: lost but not forgetting.

PMID- 15477528
TI  - Subthalamic nucleus and gait disturbance: interactions between basal ganglia and
      brainstem and spinal pathways?

PMID- 15477529
TI  - Landau-Kleffner syndrome and temporal cortical volume reduction: cause or effect?

PMID- 15477531
TI  - A focus on the synapse for neuroprotection in Alzheimer disease and other
      dementias.
AB  - Synaptic dysfunction and failure are processes that occur early in Alzheimer
      disease (AD) and are important targets for protective treatments to slow AD
      progression and preserve cognitive and functional abilities. Synaptic loss is the
      best current pathologic correlate of cognitive decline, and synaptic dysfunction
      is evident long before synapses and neurons are lost. Once synaptic function
      fails, even in the setting of surviving neurons, there may be little chance of
      effectively interfering with the disease process. This review emphasizes the
      importance of preserving synaptic structure and function (i.e.,
      "synaptoprotection") in AD. Such "synaptoprotective" therapy will probably need
      to be administered at a critical early time point, perhaps years before onset of
      clinical symptoms.

PMID- 15477532
TI  - FDA-approved neurologic devices intended for use in infants, children, and
      adolescents.
AB  - The US Food and Drug Administration (FDA) has approved several applications for
      the marketing of neurologic devices. Nineteen high risk Class III medical devices
      were approved for the central and peripheral nervous system for marketing between
      1994 and 2003, and almost half (n = 8) include indications for use in children as
      well as adults. On July 24, 2003, the FDA Center for Devices and Radiologic
      Health released for public comment a draft guidance document entitled "Premarket
      Assessment of Pediatric Medical Devices," which included in its objectives, the
      types of information needed to provide reasonable assurance of the safety and
      effectiveness of medical devices intended for use in children. The draft guidance
      document is also relevant to the types of information needed to promote the safe
      and effective development of neurologic devices. We review risk assessment and
      ways to reduce risk for neurologic devices intended for use in children. We also
      discuss the deep brain stimulator, the cochlear implant, and the CSF shunt, and
      considerations for minimizing risks associated with brain development, physical
      growth, surgery, and human factors.

PMID- 15477533
TI  - Clinical, genetic, and neuropathologic characteristics of posterior cortical
      atrophy.
AB  - OBJECTIVE: To examine the clinical, genetic, and neuropathologic features of
      posterior cortical atrophy (PCA). DESIGN/METHODS: Using a broad definition of PCA
      as a syndrome with the insidious onset of visual dysfunction in the absence of
      primary ophthalmologic causes, the authors identified and then reviewed the
      presenting signs and symptoms, ApoE genotypes, tau haplotypes, and
      neuropathologic findings when available of PCA cases from two dementia research
      centers collected over the past 14 years. RESULTS: The authors identified 40 PCA
      cases. Their mean age at symptom onset was 60.5 +/- 8.9 years. There were twice
      as many women as men in the series. The principal types of visual impairment were
      simultanagnosia (82%) and visual field defect (47.5%). Acalculia, alexia, and
      anomia were also common. Insight was preserved in almost all (95%) early in the
      disorder. Neither apoE epsilon4 nor tau haplotype frequencies were different from
      typical Alzheimer disease (AD). Nine patients had died and underwent postmortem
      examination. Seven autopsied cases had AD pathology but when compared to typical
      AD, the neurofibrillary tangle (NFT) densities were significantly higher in
      Brodmann areas 17 and 18 (p < 0.05) and significantly lower in the hippocampus (p
      < 0.05). Two cases had corticobasal degeneration with maximal involvement of tau
      positive glial pathology in the posterior parietal lobe and Brodmann areas 17 and
      18. CONCLUSIONS: PCA is a distinctive dementia syndrome in which the most
      pronounced pathologic involvement is in the occipitoparietal regions independent
      of the specific underlying pathology. AD was the most common pathologic cause,
      but its regional distribution differed from typical AD.

PMID- 15477534
TI  - Progressive posterior cortical dysfunction: a clinicopathologic series.
AB  - BACKGROUND: Atypical presentations of neurodegenerative dementing disorders
      include the syndrome of progressive posterior cortical dysfunction (PPCD)
      involving selective higher order visuospatial deficits. The neuropathologic
      correlates of PPCD remain poorly defined. METHODS: This is a retrospective case
      series of 27 individuals (14 men, 13 women) diagnosed clinically with PPCD.
      Participants were either enrolled in the Alzheimer's Disease Research Center
      (ADRC) or referred to the memory diagnostic center of an urban academic medical
      center. Clinical evaluations included physical and neurologic examinations, the
      Clinical Dementia Rating (CDR), and psychometric measures. Neuropathologic
      examinations were completed in 21 individuals with PPCD. Psychometric measures
      from 65 individuals with mild dementia of the Alzheimer type (DAT) enrolled in
      the ADRC were used for comparison. RESULTS: Neuropathologic etiologies of PPCD
      were Alzheimer disease (AD) (n = 13), AD plus Parkinson disease (n = 1), AD-Lewy
      body variant (n = 2), dementia with Lewy bodies plus progressive subcortical
      gliosis of Neumann (n = 1), corticobasal degeneration (n = 2), and prion
      associated diseases: Creutzfeldt-Jakob disease (n = 1) and fatal familial
      insomnia (n = 1). Confirming the clinical impression, psychometric profiles for
      individuals with PPCD differed from those of people with DAT alone and revealed
      disproportionate deficits on measures of visuospatial ability. CONCLUSIONS: AD
      was the most frequent cause of PPCD in this series, although non-Alzheimer's
      dementing disorders also should be considered.

PMID- 15477535
TI  - Diabetes mellitus and risk of dementia in the Kungsholmen project: a 6-year
      follow-up study.
AB  - BACKGROUND: Research on diabetes mellitus as a risk factor for dementia and its
      main subtypes has produced conflicting results. The authors investigated the
      relationship between diabetes mellitus and risk of dementia, Alzheimer disease
      (AD), and vascular dementia (VaD). METHODS: A dementia-free cohort of 1,301
      community dwellers aged 75 years and older in Stockholm, Sweden, was
      longitudinally examined twice over 6 years to detect dementia cases (Diagnostic
      and Statistical Manual of Mental Disorders-III-R diagnostic criteria). Cox
      proportional hazards models were used to analyze the data with adjustment for
      several potential confounders. RESULTS: During the 5,584 person-years of follow
      up, 350 subjects developed dementia, including 260 AD and 49 VaD cases. Diabetes
      mellitus was associated with hazard ratios (HR) of 1.5 (95% CI 1.0 to 2.1, p =
      0.04) for dementia, 2.6 (95% CI 1.2 to 6.1) for VaD, and 1.3 (95% CI 0.9 to 2.1)
      for AD. Patients who were treated with oral antidiabetic medications had HRs of
      1.7 (95% CI 1.0 to 2.8, p = 0.04) for dementia and 3.6 (95% CI 1.3 to 9.5) for
      VaD. There were significant interactions of diabetes with severe systolic
      hypertension (> or =180 mm Hg) on dementia and its main subtypes, and of diabetes
      with heart disease on VaD. CONCLUSIONS: Diabetes mellitus increases the risk of
      dementia, and VaD in particular, in very old people. The risk for dementia and
      VaD is especially high when diabetes mellitus occurs together with severe
      systolic hypertension or heart disease.

PMID- 15477536
TI  - Hyperinsulinemia and risk of Alzheimer disease.
AB  - OBJECTIVE: To explore the association between fasting insulin levels and
      dementia. METHODS: Fasting insulin levels were measured from frozen sera using
      solid-phase chemiluminescent enzyme immunoassay in a sample of elderly subjects
      chosen at random from a cohort of persons aged 65 years and older from northern
      Manhattan. Dementia was diagnosed using standard methods. Neuropsychiatric
      testing was available on all subjects at each follow-up interval. RESULTS: A
      total of 683 subjects without prevalent dementia were followed for 3,691 person
      years and 149 persons developed dementia (137 Alzheimer disease [AD], 6 dementia
      associated with stroke, 6 other). The risk of AD doubled in the 39% of the sample
      with hyperinsulinemia (HR = 2.1; 95% CI: 1.5, 2.9) and was highest in people
      without diabetes. The HR relating presence of hyperinsulinemia or diabetes in 50%
      of our sample to AD was 2.2 (95% CI: 1.5, 3.1). The risk of AD attributable to
      the presence of hyperinsulinemia or diabetes was 39%. The HR of AD for the
      highest quartile of insulin compared to the lowest was 1.7 (95% CI: 1.0, 2.7; p
      for trend = 0.009). Hyperinsulinemia was also related to a significant decline in
      memory-related cognitive scores, but not to decline in other cognitive domains.
      CONCLUSIONS: Hyperinsulinemia is associated with a higher risk of AD and decline
      in memory.

PMID- 15477537
TI  - Size does matter in the long run: hippocampal and cortical volume predict recall
      across weeks.
AB  - OBJECTIVE: To study the morphometric determinants of recall of verbal material
      for an extended period in an adult lifespan sample. METHODS: Healthy adults of
      varying ages were studied using automated segmentation of MRI scans with volumes
      of hippocampus, cortex, and white matter, and verbal memory tests assessing
      recall after 5 minutes, 30 minutes, and a mean period of 11 weeks. Stepwise
      regression analyses were performed with 5 minutes, 30 minutes, and 11-week recall
      as the dependent variables. Hippocampal, cortical, and white matter volumes were
      included in the initial set of predictor variables in each case, and the analyses
      were repeated with age as an additional predictor variable. RESULTS: When age was
      not included, cortical volume was the only variable predicting recall after 5 and
      30 minutes, whereas hippocampal and cortical volumes predicted recall after 11
      weeks. When age was included in the model, this was the only variable predicting
      recall after 5 and 30 minutes, whereas age and hippocampus gave contributions in
      prediction of recall after several weeks. CONCLUSION: This study supports a
      critical role of cortical and hippocampal size in recall. Hippocampal size seems
      more important in recall after 11 weeks than after a shorter time interval.

PMID- 15477538
TI  - Education and the course of cognitive decline in Alzheimer disease.
AB  - OBJECTIVE: To test the hypothesis that higher level of education is related to
      more rapid cognitive decline in Alzheimer disease (AD). METHODS: Participants are
      older persons with clinically diagnosed AD recruited from health care facilities
      in the Chicago area. At 6-month intervals for up to 4 years, they underwent
      uniform structured clinical evaluations that included administration of nine
      cognitive performance tests from which a composite measure of global cognition
      was derived. Analyses are based on 494 persons with follow-up data (89.3% of
      those eligible). In mixed models that allowed for linear and nonlinear decline,
      the authors first accounted for the effects of age on cognition and then tested
      the relation of education to rate of cognitive decline. RESULTS: Global cognitive
      decline had linear and nonlinear components, resulting in a gradually
      accelerating course of decline. Age was related to linear but not nonlinear
      decline, with more rapid decline observed in younger compared with older persons.
      Higher educational level was related to more rapid global cognitive decline, as
      hypothesized, with education related to the nonlinear but not the linear
      component of decline. CONCLUSION: Higher educational attainment is associated
      with a slightly accelerated rate of cognitive decline in Alzheimer disease.

PMID- 15477539
TI  - Recognition of famous faces in the medial temporal lobe: an invasive ERP study.
AB  - OBJECTIVE: To investigate the involvement of the rhinal cortex and the
      hippocampus in the processing of famous faces in contrast to nonfamous faces
      using intracranial event-related potentials (ERPs), and to analyze repetition
      effects for famous and nonfamous faces. METHODS: ERPs were elicited by pictures
      of famous and nonfamous faces and recorded from rhinal and hippocampal sites of
      intracranial electrodes in 10 presurgical patients with unilateral medial
      temporal lobe epilepsy. Famous and nonfamous faces were presented twice and mixed
      with distorted faces serving as targets. There was no instruction for an overt
      discrimination between famous and nonfamous faces. In contrast to nonfamous
      faces, famous faces stimulate processes related with access and retrieval of
      semantic memory. RESULTS: All faces evoked anterior medial temporal lobe N400
      like (AMTL-N400) potentials in the rhinal cortex and P600-like potentials in the
      hippocampus. The AMTL-N400 and the hippocampal P600 amplitudes were larger for
      famous faces than for nonfamous faces. Mean amplitudes of the first and second
      presentation of famous faces suggest a repetition effect for the rhinal sites;
      however, they are significant only in the later signal components. No repetition
      effect was found for nonfamous faces and for potentials from the hippocampus.
      CONCLUSION: The anterior medial temporal lobe N400 and the hippocampal P600 may
      be related to the access and retrieval of person-specific semantic memory.

PMID- 15477540
TI  - Diagnosis of vestibular imbalance in the blink of an eye.
AB  - BACKGROUND: In a recent study, the authors found that blinks in healthy
      volunteers always triggered ocular torsion quick phases during dynamic roll
      movements of the head. On the basis of this observation, they hypothesized that
      blinks in patients with a vestibular tone imbalance would also trigger torsional
      quick phases. METHODS: Using video-oculography with a fixation target, the
      authors recorded the ocular torsion position of the left eye of 37 participants
      while they made voluntary blinks once every 6 to 10 seconds. The participants
      were recruited from four groups: two age groups of healthy volunteers with a mean
      +/- SD age of 32 +/- 4 (n = 9) and 65 +/- 11 y (n = 9); patients with a
      unilateral vestibular disorder in an acute state (n = 12, 53 +/- 17 y); and those
      in a persisting state in which spontaneous nystagmus had already faded (n = 9, 65
      +/- 13 y). RESULTS: In the control groups of healthy volunteers, blinks triggered
      no or only small quick phases on the order of 0.1 deg. In both patient groups
      blinks always triggered quick phases with significantly higher amplitudes of 1.85
      +/- 1.02 deg and were followed by exponentially decaying slow-phases with time
      constants on the order of 1 to 2 seconds. Patients in the persisting state
      clearly differed from patients in the acute state in that their torsional
      spontaneous nystagmus had already vanished due to vestibular compensation. But
      surprisingly, these two groups did not show a large difference in terms of the
      effect of blinks on ocular torsion. The authors always observed torsional quick
      phases with the upper pole of the eye beating away from the side of the lesion.
      CONCLUSIONS: Blinks are able to trigger torsional quick phases in patients with
      both acute and persisting vestibular disorders. The side of the impairment can be
      determined from the direction in which the eye is rotated after a blink. Thus,
      ocular torsion recordings during blinks can be used as a simple clinical test for
      a vestibular tone imbalance, particularly during a persisting failure in which
      spontaneous nystagmus has resolved and can therefore no longer be used for
      diagnosis.

PMID- 15477541
TI  - PROTECT: a coordinated stroke treatment program to prevent recurrent
      thromboembolic events.
AB  - OBJECTIVE: To assess the impact of the Preventing Recurrence of Thromboembolic
      Events through Coordinated Treatment (PROTECT) Program on achievement of its
      eight secondary prevention goals at the time of discharge. METHODS: Achievement
      rates for the eight program goals at time of discharge were compared in all
      patients discharged from a university hospital-based stroke service with a
      diagnosis of ischemic stroke or TIA during a 1-year period after implementation
      of the PROTECT Program vs rates obtained from a comparable group of patients
      admitted to the same service during the preceding year. RESULTS: Demographic and
      medical features were comparable in the baseline and intervention cohorts for all
      patients with cerebral ischemia presumed due to large-vessel atherosclerosis or
      small-vessel disease (baseline year n = 117, intervention n = 130).
      Implementation rates in patients without specific contraindications increased for
      all four medication goals: 97 to 100% for antithrombotic agents, 68 to 97% for
      statins, 42 to 90% for angiotensin-converting enzyme inhibitors/angiotensin
      receptor blockers, and 14 to 70% for diuretics. Although data were not collected
      on baseline lifestyle instruction rates, instruction in the program's four
      lifestyle interventions was achieved by discharge in 100% of the intervention
      cohort. CONCLUSION: Implementation of this single-center, systems-based, in
      hospital program to initiate secondary stroke prevention therapies was associated
      with a substantial increase in treatment utilization at the time of hospital
      discharge.

PMID- 15477542
TI  - Modulation of the BOLD-response in early recovery from sensorimotor stroke.
AB  - BACKGROUND: The BOLD signal in functional MRI (fMRI) is closely related to neural
      activity. OBJECTIVE: To investigate if this relationship is disrupted after
      ischemic stroke. METHODS: BOLD activity during tactile exploration of objects was
      measured with fMRI at 1 week (subacute), 2 to 4 weeks (early chronic), and after
      1 month (chronic) after the first completed brain infarction affecting the
      sensorimotor cortex in eight patients. Functional integrity of the motor cortical
      output system was assessed with transcranial magnetic stimulation (TMS). RESULTS:
      Early after infarction the BOLD-response occurred in the adjacent cortical
      vicinity related to finger movements of the affected hand. However, during the
      early chronic stage there was a transient lack of this activation despite
      clinical improvement of hand function and preserved motor evoked potentials. The
      BOLD activity reappeared after further improvement in the chronic stage.
      CONCLUSIONS: Our findings suggest a transient hemodynamic-electrical decoupling
      in the post-ischemic cerebral cortex during the early phase of spontaneous
      clinical recovery.

PMID- 15477543
TI  - Risk of ischemic stroke with tamoxifen treatment for breast cancer: a meta
      analysis.
AB  - OBJECTIVE: To assess the overall risk of stroke, specifically ischemic stroke,
      associated with tamoxifen use by performing a meta-analysis of data reported in
      breast cancer trials. BACKGROUND: Tamoxifen increases the risk of venous
      thromboembolism in women with breast cancer, but its relationship to stroke risk
      is uncertain. METHODS: A systematic review of randomized controlled trials of
      tamoxifen for breast cancer management and prevention published since 1980 was
      performed using MEDLINE. The summary odds ratio (OR) and 95% CI were calculated
      using the Mantel-Haenszel method, followed by a statistical test for
      heterogeneity. RESULTS: Nine trials met the inclusion criteria, and six trials
      specified ischemic stroke outcomes. The Mantel-Haenszel summary OR was 1.82 (95%
      CI, 1.41 to 2.36) for ischemic stroke and 1.40 (1.14 to 1.72) for any stroke. The
      chi2 heterogeneity test was 6.0 (p > 0.1) for ischemic stroke and 16.1 (p < 0.05)
      for any stroke. The random-effects summary OR of Der Simonian and Laird for any
      stroke was 1.29 (0.92 to 1.81). During a mean follow-up period of 4.9 years, the
      frequency of ischemic stroke was 0.71% with tamoxifen vs 0.39% for controls
      (absolute increased risk, 0.32%; number needed to harm [NNH], 313). CONCLUSIONS:
      Women with breast cancer who were treated with tamoxifen had an 82% increased
      risk of ischemic stroke and a 29% increased risk of any stroke, but the absolute
      risk is small. Further studies assessing prespecified cerebrovascular outcomes
      are ongoing and will further clarify the risk of stroke associated with tamoxifen
      use.

PMID- 15477544
TI  - The effect of subthalamic nucleus stimulation on autogenic inhibition in
      Parkinson disease.
AB  - BACKGROUND: Recent animal experiments suggest an important role of descending
      input from basal ganglia to brainstem and via the reticulospinal tract (RST) to
      spinal cord in the genesis of motor symptoms in Parkinson disease (PD). In
      humans, a marker for RST activity is Ib mediated autogenic inhibition, which is
      reduced in PD patients. The authors investigated the effect of high frequency
      stimulation of the subthalamic nucleus (STN-HFS) on autogenic inhibition in PD.
      METHODS: In 10 controls and 10 PD patients with chronically implanted STN
      electrodes, the soleus H-reflex conditioned by gastrocnemius nerve stimulation
      (interstimulus interval 2 to 10 msec) was used to examine the effect of STN-HFS
      on the activity of Ib spinal interneurons. RESULTS: STN-HFS was able to restore
      the abnormally reduced autogenic inhibition. The H-reflex changes during STN-HFS
      significantly correlated with the clinical improvement of gait and posture.
      CONCLUSIONS: Observed changes in spinal autogenic inhibition may allow
      measurement of the contribution of subcortical routes to the STN-HFS induced
      motor benefit in PD.

PMID- 15477545
TI  - Incidence of parkinsonism and Parkinson disease in a general population: the
      Rotterdam Study.
AB  - OBJECTIVE: To investigate the incidence of parkinsonism and Parkinson disease
      (PD) in the general population using in-person screening along with clinical
      data. METHODS: In the Rotterdam study, a prospective population-based cohort
      study of people aged > or =55 years, the authors assessed age- and sex-specific
      incidence rates of parkinsonism and PD among 6,839 participants who were free of
      parkinsonism at baseline. Case finding involved in-person screening at baseline
      and two follow-up visits, and additional information was obtained through
      continuous monitoring of the cohort by computer linkage to general practitioners'
      and pharmacy records. RESULTS: After a mean follow-up period of 5.8 years, 132
      subjects with incident parkinsonism were identified, of whom 67 (51%) had PD. The
      incidence of parkinsonism and PD increased with age, with incidence rates for PD
      increasing from 0.3 per 1000 person-years in subjects aged 55 to 65 years, to 4.4
      per 1000 person-years for those aged > or =85 years. The overall age-adjusted
      incidence rate of any parkinsonism was not different in men and women, but men
      seem to have a higher risk for PD (male-to-female ratio, 1.54; 95% CI, 0.95 to
      2.51). CONCLUSION: Incidence rates for parkinsonism and Parkinson disease were
      higher than those reported by most previous studies, possibly because of the
      authors' intensive case-finding methods involving in-person screening.

PMID- 15477546
TI  - Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover
      study.
AB  - BACKGROUND: The long-term treatment of Parkinson disease (PD) may be complicated
      by the development of levodopa-induced dyskinesia. Clinical and animal model data
      support the view that modulation of cannabinoid function may exert an
      antidyskinetic effect. The authors conducted a randomized, double-blind, placebo
      controlled crossover trial to examine the hypothesis that cannabis may have a
      beneficial effect on dyskinesia in PD. METHODS: A 4-week dose escalation study
      was performed to assess the safety and tolerability of cannabis in six PD
      patients with levodopa-induced dyskinesia. Then a randomized placebo-controlled
      crossover study (RCT) was performed, in which 19 PD patients were randomized to
      receive oral cannabis extract followed by placebo or vice versa. Each treatment
      phase lasted for 4 weeks with an intervening 2-week washout phase. The primary
      outcome measure was a change in Unified Parkinson's Disease Rating Scale (UPDRS)
      (items 32 to 34) dyskinesia score. Secondary outcome measures included the Rush
      scale, Bain scale, tablet arm drawing task, and total UPDRS score following a
      levodopa challenge, as well as patient-completed measures of a dyskinesia
      activities of daily living (ADL) scale, the PDQ-39, on-off diaries, and a range
      of category rating scales. RESULTS: Seventeen patients completed the RCT.
      Cannabis was well tolerated, and had no pro- or antiparkinsonian action. There
      was no evidence for a treatment effect on levodopa-induced dyskinesia as assessed
      by the UPDRS, or any of the secondary outcome measures. CONCLUSIONS: Orally
      administered cannabis extract resulted in no objective or subjective improvement
      in dyskinesias or parkinsonism.

PMID- 15477547
TI  - POLG mutations in neurodegenerative disorders with ataxia but no muscle
      involvement.
AB  - OBJECTIVE: To identify POLG mutations in patients with sensory ataxia and CNS
      features. METHODS: The authors characterized clinical, laboratory, and molecular
      genetic features in eight patients from five European families. The authors
      conducted sequencing of coding exons of POLG, C10orf2 (Twinkle), and ANT1 and
      analyzed muscle mitochondrial DNA (mtDNA), including Southern blot analysis and
      long-range PCR. RESULTS: Ataxia occurred in combination with various CNS
      features, including myoclonus, epilepsy, cognitive decline, nystagmus,
      dysarthria, thalamic and cerebellar white matter lesions on MRI, and neuronal
      loss in discrete gray nuclei on autopsy. Gastrointestinal dysmotility, weight
      loss, cardiomyopathy, and valproate-induced hepatotoxicity occurred less
      frequently. Two patients died without preceding signs of progressive external
      ophthalmoplegia. In muscle, typical findings of mitochondrial disease, such as
      ragged red fibers and Southern blot mtDNA abnormalities, were absent. POLG
      mutations were present in eight patients, including two isolated cases, and one
      Finnish and two unrelated Belgian families contained in total six patients. All
      POLG mutations were recessive, occurring in a homozygous state in seven patients
      and in a compound heterozygous state in one patient. The novel W748S mutation was
      identified in five patients from three unrelated families. CONCLUSIONS: The
      clinical spectrum of recessive POLG mutations is expanded by sensory ataxic
      neuropathy, combined with variable features of involvement of CNS and other
      organs. Progressive external ophthalmoplegia, myopathy, ragged red fibers, and
      Southern blot abnormalities of muscle mitochondrial DNA also are not mandatory
      features associated with POLG mutations.

PMID- 15477548
TI  - Damage to the reticulotegmental nucleus of the pons in spinocerebellar ataxia
      type 1, 2, and 3.
AB  - BACKGROUND: The reticulotegmental nucleus of the pons (RTTG) is among the
      precerebellar nuclei of the human brainstem. Although it represents an important
      component of the oculomotor circuits crucial for the accuracy of horizontal
      saccades and the generation of horizontal smooth pursuits, the RTTG has never
      been considered in CAG repeat or polyglutamine diseases. METHODS: Thick serial
      sections through the RTTG of 10 patients with spinocerebellar ataxias (SCAs)
      assigned to the CAG repeat or polyglutamine diseases (2 SCA-1 patients, 4 SCA-2
      patients, and 4 SCA-3 patients) were stained for neuronal lipofuscin pigment and
      Nissl material. RESULTS: The unconventionally thick tissue sections revealed the
      hitherto overlooked involvement of the RTTG in the degenerative processes
      underlying SCA-1, SCA-2, and SCA-3, whereby in one of the SCA-1 patients, in two
      of the SCA-2 patients, and in all of the SCA-3 patients, the RTTG underwent a
      conspicuous loss of its nerve cells. CONCLUSIONS: Neurodegeneration may not only
      affect the cranial nerve nuclei (i.e., oculomotor and abducens nuclei) of SCA-1,
      SCA-2 and SCA-3 patients integrated into the circuits, subserving accuracy of
      horizontal saccades and the generation of horizontal smooth pursuits, but
      likewise involves the premotor networks of these circuits. This may explain why
      the SCA-1, SCA-2, and SCA-3 patients in this study with a heavily damaged
      reticulotegmental nucleus of the pons developed dysmetric horizontal saccades and
      impaired smooth pursuits during the course of the disease.

PMID- 15477549
TI  - Multifocal motor neuropathy: decrease in conduction blocks and reinnervation with
      long-term IVIg.
AB  - BACKGROUND: Multifocal motor neuropathy with conduction blocks (MMNCB) is an
      immune-mediated motor neuropathy. Previous long-term IV immunoglobulin (IVIg)
      treatment studies have documented improvement in muscle strength and functional
      disability but revealed a concomitant increase in acute axonal degeneration (AD)
      and conduction block (CB). OBJECTIVE: To determine the long-term effects of IVIg
      therapy on clinical and neurophysiologic outcome measures in MMNCB patients
      responsive to IVIg. METHODS: The authors reviewed medical records of 10 patients
      with MMNCB for outcomes in muscle strength (Medical Research Council score),
      functional disability (Modified Rankin Disability score), CB, and AD. All
      patients had received IVIg (2g/kg in 5 days for 3 consecutive months), followed
      by monthly maintenance therapy. RESULTS: Patients were followed for an average of
      7.25 years (range, 3.5 to 12 years). There was significant and sustained
      improvement in muscle strength and functional disability while on IVIg therapy.
      Furthermore, the authors found significant improvement in CB, decrease in AD, and
      evidence of reinnervation by the end of the follow-up period. CONCLUSION: Long
      term IV immunoglobulin therapy improves muscle strength and functional
      disability, decreases the number of conduction blocks and the extent of axonal
      degeneration, and promotes reinnervation. These findings differ from previous
      reports of deterioration in neurophysiologic outcome measures. Comparison of the
      IV immunoglobulin regimen in those reports and this study shows that the authors'
      patients were treated with significantly higher IV immunoglobulin maintenance
      doses. These findings have implications for the long-term treatment of patients
      with multifocal motor neuropathy with conduction blocks.

PMID- 15477550
TI  - Treatment of AIDS-associated myelopathy with L-methionine: a placebo-controlled
      study.
AB  - BACKGROUND: The histopathology of AIDS-associated myelopathy (AM) closely
      resembles that of myelopathies due to cobalamin or folate deficiency, with white
      matter vacuolization in the spinal cord. The pathogenesis of AM appears unrelated
      to direct HIV infection of the spinal cord. There is abnormal trans-methylation
      metabolism in AM, with decreased availability of the methyl group donor S
      adenosyl-methionine (SAM). The authors hypothesized that treatment with l
      methionine, the direct metabolic precursor of SAM, might improve AM. OBJECTIVE:
      To determine the safety and efficacy of l-methionine treatment in AM. METHODS:
      Fifty-six patients with clinical diagnosis of AM were randomized to a Phase II,
      double-blind, placebo-controlled study comparing the effect of l-methionine 6
      g/day in two divided doses with that of placebo. Study duration was 12 weeks. All
      patients had somatosensory evoked potentials with prolonged central conduction
      time (CCT) at entry. Change in CCT was the primary endpoint of the study.
      Frequency of adverse events (AEs) was used to assess safety. Secondary endpoints
      were strength, spasticity, and urinary function. Biochemical measurements
      included serum methionine and homocysteine and CSF SAM. RESULTS: There were no
      significant differences in AEs between the two groups. Serum homocysteine
      increased in l-methionine-treated patients from 7.2 (+/-5.2 SD) to 12.6 (+/-6.15
      SD) micromol/L. The mean CCT at baseline was 25.9 milliseconds (+/-7.3 SD) for
      the treatment group and 24.1 milliseconds (+/-7.0 SD) for the placebo group. At
      completion, it was 3.0 milliseconds (+/-6.1 SD) for the treatment group and 23.6
      milliseconds (+/-5.5 SD) for the placebo group (p = 0.17). In a subset of 15
      patients with CSF studies, SAM levels increased in the l-methionine but not in
      the placebo group (p = 0.07). There was no significant effect of treatment on
      strength, spasticity, or urinary function. CONCLUSIONS: l-methionine was safe and
      well tolerated although in some patients induced an increase of serum
      homocysteine. There was a nonsignificant improvement in CCT in treated patients
      but no benefit in any of the clinical measures.

PMID- 15477551
TI  - Chronic progressive cervical myelopathy with HTLV-I infection: Variant form of
      HAM/TSP?
AB  - OBJECTIVE: To investigate the role of human T-lymphotrophic virus type I (HTLV-I)
      infection in four patients who developed slowly progressive myelopathy with
      abnormal MRI lesions in the cervical cord levels. METHODS: Clinical and
      neuroradiologic examinations were performed, and the odds that an HTLV-I-infected
      individual of specified genotype, age, and provirus load had HTLV-I-associated
      myelopathy (HAM)/tropical spastic paraparesis (TSP) were calculated. RESULTS:
      Anti-HTLV-I antibodies were positive in both the serum and the CSF in all of the
      patients. Biopsied sample from spinal cord lesions showed inflammatory changes in
      Patient 1. Patient 2 had a demyelinating type of sensorimotor polyneuropathy. Two
      of the three patients examined showed high risk of developing HAM/TSP in
      virologic and immunologic aspects. CONCLUSION: These four cases may belong to a
      variant form of HAM/TSP, predominantly involving the cervical cord levels.

PMID- 15477552
TI  - How effective is BCNU in recurrent glioblastoma in the modern era? A phase II
      trial.
AB  - BACKGROUND: The initial studies on nitrosoureas were performed >30 years ago.
      These drugs remain the standard chemotherapy for glioblastoma. However, because
      the criteria used to evaluate the activity of nitrosoureas in a neuro-oncologic
      setting have changed, new data on their activity are needed. METHODS: The authors
      conducted a phase II study on 40 patients with recurrent glioblastoma following
      surgery and standard radiotherapy. They analyzed progression-free survival at 6
      months (PFS-6), time to progression (TTP), response rate, and toxicity. Patients
      were treated with 80 mg/m2 carmustine on days 1 to 3, every 8 weeks for a maximum
      of six cycles. RESULTS: Median TTP was 13.3 weeks (95% CI, 10.26 to 16.86 weeks),
      and PFS-6 was 17.5% (95% CI, 8.9 to 34.3). Response to chemotherapy, age < or =40
      years, and performance status > or =90 were significant prognostic factors for
      TTP; however, with multivariate analysis, only response to chemotherapy was
      significant. The major side effects were reversible hematologic and long-lasting
      hepatic and pulmonary toxicity. CONCLUSION: The activity of this BCNU regimen is
      comparable with that reported in the past and with the newest therapies, such as
      temozolomide. However, BCNU toxicity is high and recovery is slow, thus
      compromising the administration of further drugs in patients with progressive
      disease.

PMID- 15477553
TI  - Partially thrombosed aneurysm and stroke.

PMID- 15477554
TI  - A polymorphism of the hypocretin receptor 2 gene is associated with cluster
      headache.
AB  - Several polymorphisms of the hypocretin/orexin system genes were evaluated in 109
      cluster headache patients and 211 controls. The 1246 G>A polymorphism of the gene
      was significantly different between cases and controls. Homozygosity for the G
      allele was associated with an increased disease risk (OR: 6.79, 95% CI, 2.25 to
      22.99). The data suggest that the HCRTR2 gene or a linked locus significantly
      modulates the risk for cluster headache.

PMID- 15477555
TI  - Bilateral volume reduction of the superior temporal areas in Landau-Kleffner
      syndrome.
AB  - No specific anatomic abnormalities have been detected in typical Landau-Kleffner
      syndrome (LKS), an acquired epileptic aphasia with language regression in
      children. In four children with typical LKS without obvious anatomic
      abnormalities, the authors performed MRI volumetric analysis of various
      neocortical regions and subcortical substructures. Volume reduction was detected
      in bilateral superior temporal areas (26 to 51%), specifically in planum
      temporale (25 to 63%) and superior temporal gyrus (25 to 57%), where receptive
      language is localized.

PMID- 15477557
TI  - Age at onset in mesial temporal lobe epilepsy with a history of febrile seizures.
AB  - The authors demonstrated that temporal lobe epilepsy with hippocampal sclerosis
      preceded by febrile seizures can be divided into different groups according to
      age at epilepsy onset (AEO). AEO was found to be trimodal with a peak at ages
      5.5, 15.3, and 26.7. In the adolescent AEO group, a family history of epilepsy
      occurred more frequently and the age at febrile convulsions was earlier than in
      the childhood group.

PMID- 15477556
TI  - Differential localization of hamartin and tuberin and increased S6
      phosphorylation in a tuber.
AB  - In a tuberous sclerosis patient with a mutation in the TSC1 tumor suppressor
      gene, no second-hit mutation was found in a resected cortical tuber. Tuber giant
      cells showed predominantly nuclear hamartin, cytosolic tuberin, and
      hyperphosphorylation of S6. Differential accumulation of hamartin and tuberin in
      separate cellular compartments of giant cells may prevent formation of the
      hamartin-tuberin complex, resulting in increased S6 phosphorylation. These data
      provide an alternative mechanism for tuberogenesis.

PMID- 15477558
TI  - Polyomaviruses and primary central nervous system lymphomas.
AB  - The authors investigated the potential association of human primary CNS non
      Hodgkin lymphoma (PCNSL) with polyomavirus in HIV-1 infected and uninfected
      individuals. Immunohistochemical analysis of CNS biopsies from 19 HIV-negative
      and 17 HIV-positive patients and PCR analysis of 12 HIV-negative and 14 HIV
      positive patients revealed that the lymphomas were uniformly negative for
      polyomaviruses. The authors conclude that polyomaviruses are unlikely to be
      related to the pathogenesis of most PCNSL.

PMID- 15477559
TI  - Juvenile form of Alexander disease with GFAP mutation and mitochondrial
      abnormality.
AB  - The authors report a 29-year-old woman with marked atrophy of the cerebellum,
      medulla oblongata, and spinal cord, dementia, diffuse white matter abnormality on
      MRI, ragged-red fibers, and R88C mutation in the human glial fibrillary acidic
      protein (GFAP). Mitochondria DNA (mtDNA) analysis showed a rare polymorphism at
      A8291G. This mtDNA polymorphism, which has been associated with limb-girdle type
      mitochondrial myopathy, may modify the clinical symptoms of this juvenile form of
      Alexander disease with GFAP mutation.

PMID- 15477560
TI  - Mitochondrial DNA nucleotide changes in non-arteritic ischemic optic neuropathy.
AB  - The authors sequenced the entire mitochondrial DNA coding region in a group of 19
      patients with non-arteritic anterior ischemic optic neuropathy (NAION) and in 100
      controls. Synonymous and nonsynonymous nucleotide changes were more common in
      NAION patients (p < 0.001). Twelve of these (11 novel) were potentially
      pathologic, nine of which altered moderately or highly conserved amino acids in
      the functional domain of the affected protein. Mitochondrial malfunction may be a
      risk factor for NAION.

PMID- 15477561
TI  - Cluster headache and right-to-left shunt on contrast transcranial Doppler: a case
      control study.
AB  - The authors evaluated the prevalence of right-to-left shunt in 40 subjects with
      cluster headache (CH) vs 40 subjects without primary headaches or cerebrovascular
      disease. The diagnosis of shunt was made by means of transcranial Doppler with
      contrast medium. A shunt was found in 17 CH patients (42.5%) and in 7 controls
      (17.5%) (p = 0.029; OR = 3.48; 95% CI = 1.13 to 10.69).

PMID- 15477563
TI  - Ventriculoperitoneal shunting for idiopathic intracranial hypertension.
AB  - Seventeen patients treated with ventriculoperitoneal shunt (VPS) for idiopathic
      intracranial hypertension (IIH) were followed up for 1.8 to 12.8 years (mean 6.5
      years). The ventricular catheter was inserted without any guidance device. VPS
      was effective on all clinical manifestations of IIH. Seven patients required one
      or two (a total of nine) surgical revisions. The revision rate was significantly
      less than in two similar series of patients treated with lumboperitoneal shunt.

PMID- 15477562
TI  - Severe symptomatic aseptic chemical meningitis following myelography: the role of
      procalcitonin.
AB  - Symptomatic aseptic, chemical meningitis is a rare complication of myelography.
      Its acute clinical course and standard laboratory findings are indistinguishable
      from those of bacterial meningitis. The authors present a case of severe
      postmyelographic chemical meningitis and compare CSF and serum inflammatory
      markers to a group of seven patients with proven bacterial meningitis. As in
      viral meningitis, procalcitonin might be able to discriminate between bacterial
      and chemical causes of CNS inflammation.

PMID- 15477564
TI  - Multiple acute cerebral infarcts on diffusion-weighted imaging and risk of
      recurrent stroke.
AB  - Multiple acute cerebral infarcts (MACIs) detected by diffusion-weighted imaging
      (DWI) may indicate an unstable source of thromboembolism. The authors studied 119
      consecutive acute ischemic stroke patients within 24 hours of onset with DWI.
      MACIs were present in 20 patients (16.8%). During the follow-up period, there
      were 15 recurrent strokes, 3 acute coronary syndromes, and 5 deaths. MACI was the
      only significant independent predictor for vascular events and death (odd ratio
      [OR]] = 4.34; p = 0.001) and stroke recurrence (OR = 5.93; p = 0.001).

PMID- 15477565
TI  - Changes in cognitive function after neuronal cell transplantation for basal
      ganglia stroke.
AB  - Reported is the change in cognitive function after neuronal cell transplantation
      as a treatment for basal ganglia stroke. Nine subjects (two controls, seven
      transplants), all over 2 years post stroke, completed a comprehensive
      neuropsychological test battery prior to and 6 months after treatment. Four
      transplanted subjects who had strokes in the nondominant hemisphere showed marked
      improvement on the Rey Complex Figure, a test of visuospatial/constructional
      ability and nonverbal memory.

PMID- 15477566
TI  - Arrow sign in MCA trifurcation aneurysm.

PMID- 15477567
TI  - Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression.

PMID- 15477568
TI  - Ocular contrapulsion in rostral medial medullary infarction.

PMID- 15477570
TI  - What to do for the neurologist who has a screw loose: glue and the art of tuning
      fork maintenance.

PMID- 15477569
TI  - A new SBF2 mutation in a family with recessive demyelinating Charcot-Marie-Tooth
      (CMT4B2).

PMID- 15477571
TI  - A spinal cord intravascular lymphomatosis with exceptionally good outcome.

PMID- 15477572
TI  - Modern neuropsychiatric presentation of neurosyphilis.

PMID- 15477573
TI  - The neurology resident as teacher: evaluating and improving our role.
AB  - There is a need to improve the quality of teaching done by neurology residents
      because neurology residents are intimately involved in medical student education.
      This article reviews the available literature on techniques to improve the
      teaching ability of resident physicians. Eight randomized prospective studies
      were identified from health and education databases. The outcomes measured were
      student ratings of residents or objective ratings of interactions between
      residents and students. The skills curriculum provided a more robust response,
      and the objective standardized teaching examination (OSTE) provided a
      standardized outcome. There continues to be a need for studies specifically
      addressing the teaching by neurology residents and fellows.

PMID- 15477574
TI  - The quicksilver prize: mercury vapor poisoning aboard HMS Triumph and HMS Phipps.

PMID- 15477575
TI  - Antibodies to Zic4 in paraneoplastic neurologic disorders and small-cell lung
      cancer.

PMID- 15477576
TI  - Autosomal recessive, DYT2-like primary torsion dystonia: a new family.

PMID- 15477577
TI  - Importance of the imaging modality in decision making about carotid
      endarterectomy.

PMID- 15477578
TI  - Chronic daily headache with analgesic overuse: epidemiology and impact on quality
      of life.

PMID- 15477579
TI  - Pediatric neurology's midlife crisis.

PMID- 15477581
TI  - Preclinical evidence for neuroprotection with monoamine oxidase-B inhibitors in
      Parkinson's disease.

PMID- 15477582
TI  - A novel formulation of selegiline for the treatment of Parkinson's disease.

PMID- 15477583
TI  - Clinical trials of neuroprotection for Parkinson's disease.

PMID- 15477584
TI  - A review of the mechanisms and role of monoamine oxidase inhibitors in
      Parkinson's disease.

PMID- 15477585
TI  - The comparative effects of medical therapies for Parkinson's disease.

PMID- 15477586
TI  - Multiplex PCR/liquid chromatography assay for detection of gene rearrangements:
      application to RB1 gene.
AB  - Screening for large gene rearrangements is established as an important part of
      molecular medicine but is also challenging. A variety of robust methods can
      detect whole-gene deletions, but will fail to detect more subtle rearrangements
      that may involve a single exon. In this paper, we describe a new, versatile and
      robust method to assess exon copy number, called multiplex PCR/liquid
      chromatography assay (MP/LC). Multiple exons are amplified using unlabeled
      primers, then separated by ion-pair reversed-phase high-performance liquid
      chromatography (IP-RP-HPLC), and quantitated by fluorescent detection using a
      post-column intercalation dye. The relative peak intensities for each target
      directly reflect exon copy number. This novel technique was used to screen a
      panel of 121 unrelated retinoblastoma patients who were tested previously using a
      reference strategy. MP/LC correctly scored all deletions and demonstrated a
      previously undetected RB1 duplication, the first to be described. MP/LC appears
      to be an easy, versatile, and cost-effective method, which is particularly
      relevant to denaturing HPLC (DHPLC) users since it broadens the spectrum of
      available applications on a DHPLC system.

PMID- 15477587
TI  - Transforming growth factor beta-induced cell cycle arrest of human hematopoietic
      cells requires p57KIP2 up-regulation.
AB  - Transforming growth factor beta (TGFbeta) is one of few known negative regulators
      of hematopoiesis, yet the mechanisms by which it affects cell cycle arrest and
      stem cell quiescence are poorly understood. Induction of the cyclin-dependent
      kinase inhibitors, p15INK4b (p15) and p21WAF1 (p21) is important for TGFbeta
      mediated cytostasis in epithelial cells but not in hematopoietic cells. Using
      primary human hematopoietic cells and microarray analysis, we identified p57KIP2
      (p57) as the only cyclin-dependent kinase inhibitor induced by TGFbeta. Up
      regulation of p57 mRNA and protein occurs before TGFbeta-induced G1 cell cycle
      arrest, requires transcription, and is mediated via a highly conserved region of
      the proximal p57 promoter. The up-regulation of p57 is essential for TGFbeta
      induced cell cycle arrest in these cells, because two different small interfering
      RNAs that prevent p57 up-regulation block the cytostatic effects of TGFbeta on
      human hematopoietic cells. Reduction of basal p57 expression by this approach
      also allows hematopoietic cells to proliferate more readily in the absence of
      TGFbeta. p57 is a putative tumor suppressor gene whose expression is frequently
      silenced by promoter hypermethylation in hematologic malignancies. Our studies
      identify a molecular pathway by which TGFbeta mediates its cytostatic effects on
      human hematopoietic cells and suggests an explanation for the frequent silencing
      of p57 expression.

PMID- 15477588
TI  - Prion protein gene (PRNP) variants and evidence for strong purifying selection in
      functionally important regions of bovine exon 3.
AB  - Amino acid replacements encoded by the prion protein gene (PRNP) have been
      associated with transmissible and hereditary spongiform encephalopathies in
      mammalian species. However, an association between bovine spongiform
      encephalopathy (BSE) and bovine PRNP exon 3 has not been detected. Moreover,
      little is currently known regarding the mechanisms of evolution influencing the
      bovine PRNP gene. Therefore, in this study we evaluated the patterns of
      nucleotide variation associated with PRNP exon 3 for 36 breeds of domestic cattle
      and representative samples for 10 additional species of Bovinae. The results of
      our study indicate that strong purifying selection has intensely constrained PRNP
      over the long-term evolutionary history of the subfamily Bovinae, especially in
      regions considered to be of functional, structural, and pathogenic importance in
      humans as well as other mammals. The driving force behind this intense level of
      purifying selection remains to be explained.

PMID- 15477589
TI  - Exploring the potential of variola virus infection of cynomolgus macaques as a
      model for human smallpox.
AB  - Smallpox virus (variola) poses a significant threat as an agent of bioterrorism.
      To mitigate this risk, antiviral drugs and an improved vaccine are urgently
      needed. Satisfactory demonstration of protective efficacy against authentic
      variola will require development of an animal model in which variola produces a
      disease course with features consistent with human smallpox. Toward this end,
      cynomolgus macaques were exposed to several variola strains through aerosol
      and/or i.v. routes. Two strains, Harper and India 7124, produced uniform acute
      lethality when inoculated i.v. in high doses (10(9) plaque-forming units). Lower
      doses resulted in less fulminant, systemic disease and lower mortality. Animals
      that died had profound leukocytosis, thrombocytopenia, and elevated serum
      creatinine levels. After inoculation, variola was disseminated by means of a
      monocytic cell-associated viremia. Distribution of viral antigens by
      immunohistochemistry correlated with the presence of replicating viral particles
      demonstrated by electron microscopy and pathology in the lymphoid tissues, skin,
      oral mucosa, gastrointestinal tract, reproductive system, and liver. These
      particles resembled those seen in human smallpox. High viral burdens in target
      tissues were associated with organ dysfunction and multisystem failure. Evidence
      of coagulation cascade activation (D dimers) corroborated histologic evidence of
      hemorrhagic diathesis. Depletion of T cell-dependent areas of lymphoid tissues
      occurred, probably as a consequence of bystander apoptotic mechanisms initiated
      by infected macrophages. Elaboration of cytokines, including IL-6 and IFN-gamma,
      contribute to a cytokine storm formerly known as "toxemia." A more precise
      understanding of disease pathogenesis should provide targets for therapeutic
      intervention, to be used alone or in combination with inhibitors of variola virus
      replication.

PMID- 15477590
TI  - The host response to smallpox: analysis of the gene expression program in
      peripheral blood cells in a nonhuman primate model.
AB  - Smallpox has played an unparalleled role in human history and remains a
      significant potential threat to public health. Despite the historical
      significance of this disease, we know little about the underlying pathophysiology
      or the virulence mechanisms of the causative agent, variola virus. To improve our
      understanding of variola pathogenesis and variola-host interactions, we examined
      the molecular and cellular features of hemorrhagic smallpox in cynomolgus
      macaques. We used cDNA microarrays to analyze host gene expression patterns in
      sequential blood samples from each of 22 infected animals. Variola infection
      elicited striking and temporally coordinated patterns of gene expression in
      peripheral blood. Of particular interest were features that appear to represent
      an IFN response, cell proliferation, immunoglobulin gene expression, viral dose
      dependent gene expression patterns, and viral modulation of the host immune
      response. The virtual absence of a tumor necrosis factor alpha/NF-kappaB
      activated transcriptional program in the face of an overwhelming systemic
      infection suggests that variola gene products may ablate this response. These
      results provide a detailed picture of the host transcriptional response during
      smallpox infection, and may help guide the development of diagnostic,
      therapeutic, and prophylactic strategies.

PMID- 15477591
TI  - Growth retardation and abnormal maternal behavior in mice lacking testicular
      orphan nuclear receptor 4.
AB  - Testicular orphan nuclear receptor 4 (TR4) is a member of the nuclear receptor
      superfamily for which a ligand has not yet been found. In vitro data obtained
      from various cell lines suggest that TR4 functions as a master regulator to
      modulate many signaling pathways, yet the in vivo physiological roles of TR4
      remain unclear. Here, we report the generation of mice lacking TR4 by means of
      targeted gene disruption (TR4(-/-)). The number of TR4(-/-) pups generated by the
      mating of TR4(+/-) mice is well under that predicted by the normal Mendelian
      ratio, and TR4(-/-) mice demonstrate high rates of early postnatal mortality, as
      well as significant growth retardation. Additionally, TR4(-/-) females show
      defects in reproduction and maternal behavior, with pups of TR4(-/-) dams dying
      soon after birth with no indication of milk intake. These results provide in vivo
      evidence that TR4 plays important roles in growth, embryonic and early postnatal
      pup survival, female reproductive function, and maternal behavior.

PMID- 15477592
TI  - Codon-specific translational defect caused by a wobble modification deficiency in
      mutant tRNA from a human mitochondrial disease.
AB  - Point mutations in the mitochondrial (mt) tRNA(Leu(UUR)) gene are responsible for
      mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
      (MELAS), a subgroup of mitochondrial encephalomyopathic diseases. We previously
      showed that mt tRNA(Leu(UUR)) with an A3243G or T3271C mutation derived from
      patients with MELAS are deficient in a normal taurine-containing modification
      (taum5U; 5-taurinomethyluridine) at the anticodon wobble position. To examine
      decoding disorder of the mutant tRNA due to the wobble modification deficiency
      independent of the pathogenic point mutation itself, we used a molecular surgery
      technique to construct an mt tRNA(Leu(UUR)) molecule lacking the taurine
      modification but without the pathogenic mutation. This "operated" mt
      tRNA(Leu(UUR)) without the taurine modification showed severely reduced UUG
      translation but no decrease in UUA translation. We thus concluded that the UUG
      codon-specific translational defect of the mutant mt tRNAs(Leu(UUR)) is the
      primary cause of MELAS at the molecular level. This result could explain the
      complex I deficiency observed clinically in MELAS.

PMID- 15477593
TI  - A rapid bioassay for single bacterial cell quantitation using bioconjugated
      nanoparticles.
AB  - The rapid and sensitive determination of pathogenic bacteria is extremely
      important in biotechnology, medical diagnosis, and the current fight against
      bioterrorism. Current methods either lack ultrasensitivity or take a long time
      for analysis. Here, we report a bioconjugated nanoparticle-based bioassay for in
      situ pathogen quantification down to single bacterium within 20 min. The
      bioconjugated nanoparticle provides an extremely high fluorescent signal for
      bioanalysis and can be easily incorporated with biorecognition molecules, such as
      antibody. The antibody-conjugated nanoparticles can readily and specifically
      identify a variety of bacterium, such as Escherichia coli O157:H7, through
      antibody-antigen interaction and recognition. The single-bacterium-detection
      capability within 20 min has been confirmed by the plate-counting method and
      realized by using two independent optical techniques. The two detection methods
      correlated extremely well. Furthermore, we were able to detect multiple bacterial
      samples with high throughput by using a 384-well microplate format. To show the
      usefulness of this assay, we have accurately detected 1-400 E. coli O157
      bacterial cells in spiked ground beef samples. Our results demonstrate the
      potential for a broad application of bioconjugated nanoparticles in practical
      biotechnological and medical applications in various biodetection systems. The
      ultimate power of integrating bionanotechnology into complex biological systems
      will emerge as a revolutionary tool for ultrasensitive detection of disease
      markers and infectious agents.

PMID- 15477594
TI  - Upstream binding factor association induces large-scale chromatin decondensation.
AB  - The function of upstream binding factor (UBF), an essential component of the RNA
      polymerase (pol) I preinitiation complex, is unclear. Recently, UBF was found
      distributed throughout ribosomal gene repeats rather than being restricted to
      promoter regions. This observation has led to the speculation that one role of
      UBF binding may be to induce chromatin remodeling. To directly evaluate the
      impact of UBF on chromatin structure, we used an in vivo assay in which UBF is
      targeted via a lac repressor fusion protein to a heterochromatic, amplified
      chromosome region containing lac operator repeats. We show that the association
      of UBF with this locus induces large-scale chromatin decondensation. This process
      does not appear to involve common remodeling complexes, including SWI/SNF and
      histone acetyltransferases, and is independent of histone H3 lysine 9
      acetylation. However, UBF recruits the pol I-specific, TATA box-binding protein
      containing complex SL1 and pol I subunits. Our results suggest a working
      hypothesis in which the dynamic association of UBF with ribosomal DNA clusters
      recruits the pol I transcription machinery and maintains these loci in a
      transcriptionally competent configuration. These studies also provide an in vivo
      model simulating ribosomal DNA transactivation outside the nucleolus, allowing
      temporal and spatial analyses of chromatin remodeling and assembly of the pol I
      transcription machinery.

PMID- 15477595
TI  - Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human
      HDAC8, complexed with a hydroxamic acid inhibitor.
AB  - Histone deacetylases (HDACs) are a family of enzymes involved in the regulation
      of gene expression, DNA repair, and stress response. These processes often are
      altered in tumors, and HDAC inhibitors have had pronounced antitumor activity
      with promising results in clinical trials. Here, we report the crystal structure
      of human HDAC8 in complex with a hydroxamic acid inhibitor. Such a structure of a
      eukaryotic zinc-dependent HDAC has not be described previously. Similar to
      bacterial HDAC-like protein, HDAC8 folds in a single alpha/beta domain. The
      inhibitor and the zinc-binding sites are similar in both proteins. However,
      significant differences are observed in the length and structure of the loops
      surrounding the active site, including the presence of two potassium ions in
      HDAC8 structure, one of which interacts with key catalytic residues. CD data
      suggest a direct role of potassium in the fold stabilization of HDAC8. Knockdown
      of HDAC8 by RNA interference inhibits growth of human lung, colon, and cervical
      cancer cell lines, highlighting the importance of this HDAC subtype for tumor
      cell proliferation. Our findings open the way for the design and development of
      selective inhibitors of HDAC8 as possible antitumor agents.

PMID- 15477596
TI  - Melanin acts as a potent UVB photosensitizer to cause an atypical mode of cell
      death in murine skin.
AB  - Melanin protects the skin against DNA damage induced by direct absorption of
      sunlight's UV radiation. Yet, irradiating melanin in vitro or in cultured cells
      also generates active oxygen species such as superoxide, which can indirectly
      induce oxidative base lesions and DNA strand breaks. This photosensitization is
      greater for pheomelanin (yellow and red melanin) than for eumelanin (brown and
      black). The in vivo photosensitizing ability of melanin is unknown. We used
      congenic mice of black, yellow, and albino coat colors to investigate the
      induction of DNA lesions and apoptosis after exposure to predominantly UVB (280
      320 nm) or UVA (320-400 nm) radiation. Cyclobutane pyrimidine dimers induced by
      direct UVB absorption were equal in all three strains, as was apoptosis measured
      as sunburn cells or as keratinocytes containing active caspase-3. However,
      terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL)
      positive cells were approximately 3-fold more frequent in black and yellow mice
      after UVB or UVA irradiation than in albino. In epidermal sheets, TUNEL-positive
      cells lined the upper portion of the hair follicle, consistent with UV-induced
      photosensitization by melanin in the hair shaft. Because the concentration of
      eumelanin in black mice was three times that of pheomelanin in yellow mice,
      pheomelanin had 3-fold greater specific activity. We conclude that UV-irradiated
      melanin, particularly pheomelanin, photosensitizes adjacent cells to caspase-3
      independent apoptosis, and this occurs at a frequency greater than the apoptosis
      induced by direct DNA absorption of UV. Melanin-induced apoptosis may contribute
      to the increased sensitivity of individuals with blonde and red hair to sunburn
      and skin cancer.

PMID- 15477597
TI  - Most species are not driven to extinction before genetic factors impact them.
AB  - There is controversy concerning the role of genetic factors in species
      extinctions. Many authors have asserted that species are usually driven to
      extinction before genetic factors have time to impact them, but few studies have
      seriously addressed this issue. If this assertion is true, there will be little
      difference in genetic diversity between threatened and taxonomically related
      nonthreatened species. We compared average heterozygosities in 170 threatened
      taxa with those in taxonomically related nonthreatened taxa in a comprehensive
      metaanalysis. Heterozygosity was lower in threatened taxa in 77% of comparisons,
      a highly significant departure from the predictions of the no genetic impact
      hypothesis. Heterozygosity was on average 35% lower (median 40%) in threatened
      taxa than in related nonthreatened ones. These differences in heterozygosity
      indicate lowered evolutionary potential, compromised reproductive fitness, and
      elevated extinction risk in the wild. Independent evidence from stochastic
      computer projections has demonstrated that inbreeding depression elevates
      extinction risk for threatened species in natural habitats when all other
      threatening processes are included in the models. Thus, most taxa are not driven
      to extinction before genetic factors affect them adversely.

PMID- 15477598
TI  - IL-15/IL-15Ralpha-mediated avidity maturation of memory CD8+ T cells.
AB  - T cell avidity is critical to viral clearance, but mechanisms of CD8(+) T cell
      avidity maturation are poorly understood. Here, we find that IL-15 mediates two
      mechanisms of avidity maturation. (i) By selection at the population level, IL-15
      promotes greater survival of high- compared with low-avidity cytotoxic T
      lymphocytes (CTLs). High-avidity CTLs express higher levels of IL-15Ralpha and
      persist longer by homeostatic proliferation. (ii) At the individual cell level,
      IL-15 induces higher levels of surface coreceptor CD8alphabeta, increasing
      functional avidity. IL-15 during priming selects or induces higher-avidity CTLs.
      Conversely, high-avidity CTLs are diminished in IL-15Ralpha knockout mice. These
      results provide an explanation of CD8+ T cell avidity maturation and may
      contribute to the design of novel vaccines.

PMID- 15477599
TI  - Stem cell expression of the AML1/ETO fusion protein induces a myeloproliferative
      disorder in mice.
AB  - The t(8;21)(q22;q22) translocation, present in 10-15% of acute myeloid leukemia
      (AML) cases, generates the AML1/ETO fusion protein. To study the role of AML1/ETO
      in the pathogenesis of AML, we used the Ly6A locus that encodes the well
      characterized hematopoietic stem cell marker, Sca1, to target expression of
      AML1/ETO to the hematopoietic stem cell compartment in mice. Whereas germ-line
      expression of AML1/ETO from the AML1 promoter results in embryonic lethality,
      heterozygous Sca1(+/AML1-ETO ires EGFP) (abbreviated Sca(+/AE)) mutant mice are
      born in Mendelian ratios with no apparent abnormalities in growth or fertility.
      Hematopoietic cells from Sca(+/AE) mice have markedly extended survival in vitro
      and increasing myeloid clonogenic progenitor output over time. Sca(+/AE) mice
      develop a spontaneous myeloproliferative disorder with a latency of 6 months and
      a penetrance of 82% at 14 months. These results reinforce the notion that the
      phenotype of murine transgenic models of human leukemia is critically dependent
      on the cellular compartment targeted by the transgene. This model should provide
      a useful platform to analyze the effect of AML1/ETO on hematopoiesis and its
      potential cooperation with other mutations in the pathogenesis of leukemia.

PMID- 15477600
TI  - Forecast and control of epidemics in a globalized world.
AB  - The rapid worldwide spread of severe acute respiratory syndrome demonstrated the
      potential threat an infectious disease poses in a closely interconnected and
      interdependent world. Here we introduce a probabilistic model that describes the
      worldwide spread of infectious diseases and demonstrate that a forecast of the
      geographical spread of epidemics is indeed possible. This model combines a
      stochastic local infection dynamics among individuals with stochastic transport
      in a worldwide network, taking into account national and international civil
      aviation traffic. Our simulations of the severe acute respiratory syndrome
      outbreak are in surprisingly good agreement with published case reports. We show
      that the high degree of predictability is caused by the strong heterogeneity of
      the network. Our model can be used to predict the worldwide spread of future
      infectious diseases and to identify endangered regions in advance. The
      performance of different control strategies is analyzed, and our simulations show
      that a quick and focused reaction is essential to inhibiting the global spread of
      epidemics.

PMID- 15477601
TI  - Cell division and cell survival in the absence of survivin.
AB  - The survivin protein contains structural features of the inhibitor of apoptosis
      protein family. Previous studies have suggested that survivin is essential for
      cell survival because it counteracts an otherwise constitutive propensity to
      apoptosis during mitosis. In addition, survivin appears to be a component of the
      chromosomal passenger protein complex that participates in multiple facets of
      cell division. Here we report that euploid human cells do not die in the absence
      of survivin. Instead, depletion of survivin caused defects in cell division,
      followed by an arrest of DNA synthesis due to activation of a checkpoint
      involving the tumor suppressor protein p53. During anaphase mitosis in survivin
      deficient cells, sister chromatids disjoined normally, but one or more of the
      sister chromatids frequently lagged behind the main mass of segregating
      chromosomes, probably because of merotelic kinetochore attachments. Survivin
      deficient cells initiated but failed to complete cytokinesis, apparently because
      the spindle midzone and midbody microtublues were absent during late mitosis. The
      abnormalities of both chromosome segregation and cytokinesis could be attributed
      to a defect in the chromosomal passenger protein complex, with a consequent
      mislocalization of the kinesin-like motor protein MKLP-1 playing a more immediate
      role in the microtubule abnormalities. Depletion of another chromosomal passenger
      protein, aurora-B, recapitulated the survivin RNA interference phenotypes. We
      conclude that survivin can be essential for the proliferation of normal human
      cells by virtue of its contributions to accurate sister chromatid segregation and
      assembly/stabilization of microtubules in late mitosis. However, the protein is
      not inevitably required for the survival of normal cells.

PMID- 15477603
TI  - Crystal structure of gamma-glutamylcysteine synthetase: insights into the
      mechanism of catalysis by a key enzyme for glutathione homeostasis.
AB  - Gamma-glutamylcysteine synthetase (gammaGCS), a rate-limiting enzyme in
      glutathione biosynthesis, plays a central role in glutathione homeostasis and is
      a target for development of potential therapeutic agents against parasites and
      cancer. We have determined the crystal structures of Escherichia coli gammaGCS
      unliganded and complexed with a sulfoximine-based transition-state analog
      inhibitor at resolutions of 2.5 and 2.1 A, respectively. In the crystal structure
      of the complex, the bound inhibitor is phosphorylated at the sulfoximido nitrogen
      and is coordinated to three Mg2+ ions. The cysteine-binding site was identified;
      it is formed inductively at the transition state. In the unliganded structure, an
      open space exists around the representative cysteine-binding site and is probably
      responsible for the competitive binding of glutathione. Upon inhibitor binding,
      the side chains of Tyr-241 and Tyr-300 turn, forming a hydrogen-bonding triad
      with the carboxyl group of the inhibitor's cysteine moiety, allowing this moiety
      to fit tightly into the cysteine-binding site with concomitant accommodation of
      its side chain into a shallow pocket. This movement is caused by a conformational
      change of a switch loop (residues 240-249). Based on this crystal structure, the
      cysteine-binding sites of mammalian and parasitic gammaGCSs were predicted by
      multiple sequence alignment, although no significant sequence identity exists
      between the E. coli gammaGCS and its eukaryotic homologues. The identification of
      this cysteine-binding site provides important information for the rational design
      of novel gammaGCS inhibitors.

PMID- 15477605
TI  - The Romanow gaps: some closing, others still open.

PMID- 15477604
TI  - RNA polymerase I remains intact without subunit exchange through multiple rounds
      of transcription in Saccharomyces cerevisiae.
AB  - Previous experiments using mammalian cells suggested that after each round of
      transcription, RNA polymerase I (Pol I) dissociates into subunits that leave and
      reenter the nucleolus as individual subunits, before formation of a new
      initiation complex. In this study, we show that the size and subunit composition
      of Pol I did not change significantly when Pol I was not engaged in rRNA
      transcription, brought about by either the absence of Pol I-specific rDNA
      template or specific inhibition of the transcription initiation step that
      requires Rrn3p. In fact, Pol I purified from cells completely lacking rDNA
      repeats was more active than when purified from wild-type cells in an in vitro
      transcription system designed to assay active Pol I-Rrn3p complexes. Furthermore,
      measurements of the exchange of A135 and A190 subunits between preexistent Pol I
      and newly synthesized Pol I showed that these two largest subunits of Pol I do
      not disassociate through many rounds of transcription in vivo. Thus, Pol I is not
      a dynamic protein complex but rather a stable enzyme.

PMID- 15477606
TI  - Canadian Adverse Events Study.

PMID- 15477608
TI  - Nuts, omega-3s and food labels.

PMID- 15477609
TI  - Canadian Adverse Events Study.

PMID- 15477610
TI  - Canadian adverse events study.

PMID- 15477602
TI  - Nucleotide diversity and linkage disequilibrium in loblolly pine.
AB  - Outbreeding species with large, stable population sizes, such as widely
      distributed conifers, are expected to harbor relatively more DNA sequence
      polymorphism. Under the neutral theory of molecular evolution, the expected
      heterozygosity is a function of the product 4N(e)mu, where N(e) is the effective
      population size and mu is the per-generation mutation rate, and the genomic scale
      of linkage disequilibrium is determined by 4N(e)r, where r is the per-generation
      recombination rate between adjacent sites. These parameters were estimated in the
      long-lived, outcrossing gymnosperm loblolly pine (Pinus taeda L.) from a survey
      of single nucleotide polymorphisms across approximately 18 kb of DNA distributed
      among 19 loci from a common set of 32 haploid genomes. Estimates of 4N(e)mu at
      silent and nonsynonymous sites were 0.00658 and 0.00108, respectively, and both
      were statistically heterogeneous among loci. By Tajima's D statistic, the site
      frequency spectrum of no locus was observed to deviate from that predicted by
      neutral theory. Substantial recombination in the history of the sampled alleles
      was observed and linkage disequilibrium declined within several kilobases. The
      composite likelihood estimate of 4N(e)r based on all two-site sample
      configurations equaled 0.00175. When geological dating, an assumed generation
      time (25 years), and an estimated divergence from Pinus pinaster Ait. are used,
      the effective population size of loblolly pine should be 5.6 x 10(5). The
      emerging narrow range of estimated silent site heterozygosities (relative to the
      vast range of population sizes) for humans, Drosophila, maize, and pine parallels
      the paradox described earlier for allozyme polymorphism and challenges simple
      equilibrium models of molecular evolution.

PMID- 15477611
TI  - Canadian Adverse Events Study.

PMID- 15477613
TI  - Canadian Adverse Events Study.

PMID- 15477614
TI  - FDA urges "black box" warning on pediatric antidepressants.

PMID- 15477619
TI  - Intracytoplasmic sperm injection: promises and challenges.

PMID- 15477620
TI  - Still waiting for health reform.

PMID- 15477621
TI  - Sports dermatology part 1: common dermatoses.

PMID- 15477622
TI  - Upsurge of genital Chlamydia trachomatis infection.

PMID- 15477623
TI  - Fever after aortic valve replacement in a 71-year-old man.

PMID- 15477624
TI  - Apolipoprotein E epsilon4 genotype as a risk factor for cognitive decline and
      dementia: data from the Canadian Study of Health and Aging.
AB  - BACKGROUND: Apolipoprotein E (ApoE) epsilon4 genotype is a well-established risk
      factor for Alzheimer's disease (AD). However, its effect on predicting conversion
      from normal to "cognitive impairment, no dementia" (CIND) and from CIND to AD is
      less clear. METHODS: We used a nested case-control design from the population
      based Canadian Study of Health and Aging (CSHA) to examine the effect of ApoE
      epsilon4 genotype on the conversion of subjects from normal to CIND and from CIND
      to AD. We also contrasted these findings with incident cases of AD and vascular
      dementia (VaD) in the CSHA cohort. RESULTS: The ApoE epsilon4 genotype was a
      significant risk factor for conversion from CIND to AD and from normal to AD and
      VaD. However, it was not a significant risk factor for conversion from normal to
      CIND. This effect is robust to adjustment for age, sex and education level. There
      is significant interaction between the ApoE epsilon4 genotype and age for AD and
      for conversion from CIND to AD. No interaction between ApoE epsilon4 genotype,
      sex, age, ethnicity and education level was found in other subgroup analyses. The
      positive predictive value of ApoE epsilon4 for predicting CIND conversion to AD
      was 0.48, and the negative predictive value was 0.65. INTERPRETATION: Possession
      of an ApoE epsilon4 allele increases the risk of AD developing from CIND. It is
      also associated with a decrease in the age at onset of AD. Its predictive values
      do not support its utility as a diagnostic test for predicting progression from
      CIND to AD, but it may be useful in research studies to enrich study samples that
      have a higher rate of progression to AD.

PMID- 15477625
TI  - Fracture risk among First Nations people: a retrospective matched cohort study.
AB  - BACKGROUND: Canadian First Nations people have unique cultural, socioeconomic and
      health-related factors that may affect fracture rates. We sought to determine the
      overall and site-specific fracture rates of First Nations people compared with
      non-First Nations people. METHODS: We studied fracture rates among First Nations
      people aged 20 years and older (n = 32 692) using the Manitoba administrative
      health database (1987-1999). We used federal and provincial sources to identify
      ethnicity, and we randomly matched each First Nations person with 3 people of the
      same sex and year of birth who did not meet this definition of First Nations
      ethnicity (n = 98 076). We used a provincial database of hospital separations and
      physician billing claims to calculate standardized incidence ratios (SIRs) and
      95% confidence intervals (CIs) for each fracture type based on a 5-year age
      strata. RESULTS: First Nations people had significantly higher rates of any
      fracture (age- and sex-adjusted SIR 2.23, 95% CI 2.18-2.29). Hip fractures (SIR
      1.88, 95% CI 1.61-2.14), wrist fractures (SIR 3.01, 95% CI 2.63-3.42) and spine
      fractures (SIR 1.93, 95% CI 1.79-2.20) occurred predominantly in older people and
      women. In contrast, craniofacial fractures (SIR 5.07, 95% CI 4.74-5.42) were
      predominant in men and younger adults. INTERPRETATION: First Nations people are a
      previously unidentified group at high risk for fracture.

PMID- 15477626
TI  - Informed consent for uninsured services: a primary care perspective on the new
      childhood vaccines.

PMID- 15477627
TI  - The benefits of apolipoprotein E epsilon4 screening to research.

PMID- 15477628
TI  - Physician remuneration in industry-sponsored clinical trials: the case for
      standardized clinical trial budgets.

PMID- 15477629
TI  - Randomized clinical trials: slow death by a thousand unnecessary policies?

PMID- 15477631
TI  - Homocysteine and cognitive function in elderly people.
AB  - Dementia is highly prevalent among elderly people, and projections show that the
      number of people affected might triple over the next 50 years, mainly because of
      a large increase in the oldest-old segment of the population. Because of this and
      the disease's devastating effects, measures for the prevention and early
      detection of dementia are crucial. Age and years of education are among the most
      relevant risk factors for dementia, but in recent years the role of homocysteine
      has also been investigated. Homocysteine is an amino acid produced in the
      metabolism of methionine, a process dependent on the B vitamins cobalamin,
      vitamin B6 and folic acid. There is evidence that increased serum homocysteine
      levels are associated with declining cognitive function and dementia. We review
      this evidence in addition to the potential mechanisms through which homocysteine
      acts on the brain to cause cognitive dysfunction, the metabolism of homocysteine
      and factors associated with alteration of the normal metabolism.

PMID- 15477632
TI  - FDA drug approval summaries: pemetrexed (Alimta).
AB  - The purpose of this report is to summarize information on pemetrexed (LY231514;
      MTA; Alimta; Eli Lilly and Company; Indianapolis, IN), a drug recently approved
      by the U.S. Food and Drug Administration (FDA). The review of the efficacy and
      safety of pemetrexed is summarized below. Pemetrexed is a pyrrolopyrimidine
      antifolate. It inhibits thymidylate synthase, glycinamide ribonucleotide
      formyltransferase, and dihydrofolate reductase. In a single, randomized, single
      blind, multicenter phase III trial, the efficacy and safety of pemetrexed
      combined with cisplatin (Platinol; Bristol-Myers Squibb; Princeton, NJ) were
      compared with those of single-agent cisplatin in 448 patients with malignant
      pleural mesothelioma. Two hundred twenty-six patients were randomized to receive
      pemetrexed and cisplatin, while 222 patients were randomized to receive cisplatin
      alone. The primary study end point was survival. Median survival times were 12.1
      months for the pemetrexed plus cisplatin treated arm and 9.3 months for the
      cisplatin alone arm. Pemetrexed causes myelosuppression. The most common adverse
      events were neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting. On
      February 4, 2004, pemetrexed was approved by the FDA in combination with
      cisplatin for the treatment of patients with malignant pleural mesothelioma whose
      disease is unresectable or who are otherwise not candidates for curative surgery.
      The recommended dose of pemetrexed is 500 mg/m(2) administered as an i.v.
      infusion over 10 minutes on day 1 of each 21-day cycle together with cisplatin at
      a dose of 75 mg/m(2) infused over 2 hours beginning 30 minutes after the
      pemetrexed infusion. Patients must receive oral folic acid and vitamin B(12)
      injections prior to the start of therapy and continue these during therapy to
      reduce severe toxicities. Patients should also receive corticosteroids with
      chemotherapy to reduce the risk of skin rashes. Approval was based on superior
      survival as a clinical benefit.

PMID- 15477633
TI  - Superiority of letrozole to tamoxifen in the first-line treatment of advanced
      breast cancer: evidence from metastatic subgroups and a test of functional
      ability.
AB  - PURPOSE: The letrozole study 025 is a large (n = 907), international, double
      blind, randomized, phase III trial in postmenopausal women with advanced breast
      cancer. This subanalysis compares the efficacies of letrozole and tamoxifen as
      first-line therapy in postmenopausual women with advanced breast cancer according
      to site of metastatic lesions and Karnofsky Performance Status (KPS). MATERIALS
      AND METHODS: Nine hundred seven patients with advanced breast cancer were
      randomly assigned to once-daily oral letrozole (2.5 mg; Femara; Novartis Pharma
      AG; Basel, Switzerland) or tamoxifen (20 mg; Tamofen; Leiras OY; Turku, Finland).
      Time to progression (TTP) was estimated using the Kaplan-Meier product-limit
      method. Treatments were compared by Cox proportional hazards regression models.
      RESULTS: Letrozole treatment significantly prolonged TTP in all subsets of
      patients: those with nonvisceral metastases, those with visceral metastases
      without liver involvement, and those with liver metastases. The reduction in risk
      of progression ranged from 25%, for patients with nonvisceral metastases, to 36%,
      for patients with liver metastases. The distributions of baseline KPS scores for
      both treatment groups were similar (57% had KPS scores >/=90). Time to worsening
      of 20 points or more in KPS score was significantly longer with letrozole than
      with tamoxifen, but modest numbers of patients experienced such deterioration
      (letrozole, 20%, tamoxifen, 22%, in patients without visceral metastases; 23%-24%
      in patients with liver metastases; and letrozole, 14%, tamoxifen, 30%, in
      patients with visceral metastases without liver involvement). CONCLUSION: These
      data demonstrate the consistent superiority of letrozole over tamoxifen and
      support the use of letrozole as a new standard of endocrine therapy in
      postmenopausal women with advanced breast cancer.

PMID- 15477634
TI  - Efficacy of first-line letrozole versus tamoxifen as a function of age in
      postmenopausal women with advanced breast cancer.
AB  - PURPOSE: To compare the efficacy, in regard to time to progression (TTP) and
      objective response rate (ORR), of letrozole (Femara; Novartis Pharma AG; Basel
      Switzerland), an oral aromatase inhibitor, with that of tamoxifen (Tamofen;
      Leiras OY; Turku, Finland) as first-line therapy in younger (<70 years) and older
      (>/=70 years) postmenopausal women with advanced breast cancer. MATERIALS AND
      METHODS: Nine hundred seven patients with advanced breast cancer were randomly
      assigned to receive 2.5 mg letrozole (n = 453) or 20 mg tamoxifen (n = 454) once
      daily in a double-blind, multicenter, international trial. Among the
      prospectively planned analyses were analyses of TTP and ORR by age (<70 and >/=70
      years). The results of these prospectively planned analyses are reported here.
      RESULTS: Letrozole was as effective in older postmenopausal women (>/=70 years of
      age) as it was in younger postmenopausal women (<70 years of age). The overall
      ORR in the older subgroup was significantly higher in patients treated with
      letrozole (38%) than in patients treated with tamoxifen (18%). In the younger
      subgroup of postmenopausal patients, the ORRs were not significantly different
      (letrozole, 26%; tamoxifen, 22%). TTP was significantly longer for letrozole than
      for tamoxifen in both age groups (younger: letrozole median TTP, 8.8 months;
      tamoxifen, 6.0 months; older: letrozole median TTP, 12.2 months; tamoxifen, 5.8
      months). Although age was independently prognostic of TTP, there was no
      significant effect of age on ORR in the presence of other factors. CONCLUSION:
      The data show that letrozole, 2.5 mg once daily, is as effective in older,
      postmenopausal women as it is in younger postmenopausal women with advanced
      breast cancer. In addition, letrozole was more effective than tamoxifen in both
      younger and older patients.

PMID- 15477635
TI  - What is the role of ovarian ablation in the management of primary and metastatic
      breast cancer today?
AB  - Ovarian ablation has been used for more than a century in the treatment of breast
      cancer. Methods of irreversible ovarian ablation include surgical oophorectomy
      and ovarian irradiation. Potentially reversible castration can be accomplished
      medically using luteinizing hormone releasing hormone (LHRH) analogues. In
      addition, cytotoxic chemotherapy unpredictably produces amenorrhea and primary
      ovarian failure in 10%-95% of premenopausal women as a function of patient age,
      cumulative dose, and the specific agents used. In the metastatic setting, ovarian
      ablation and tamoxifen monotherapies produce comparable outcomes and may be more
      effective when used together. While many early adjuvant trials of ovarian
      ablation were methodologically flawed, a more recent meta-analysis by the Early
      Breast Cancer Trialists' Collaborative Group of 12 properly designed randomized
      trials found significantly greater disease-free and overall survival rates for
      women under the age of 50, regardless of nodal status, receiving ovarian ablation
      as a single adjuvant therapy. Several important issues regarding the role of
      ovarian ablation in the treatment of breast cancer remain unresolved. Data
      suggest that ovarian ablation followed by some years of tamoxifen produces
      similar results to those seen with adjuvant chemotherapy in women with hormone
      receptor positive breast cancer; however, the value of combining these modalities
      is still unclear. Other areas of ongoing investigation include the appropriate
      duration of therapy with LHRH analogues in the adjuvant setting, the long-term
      sequelae of ovarian suppression among young breast cancer survivors, and
      refinement of the population most likely to benefit from ovarian ablation or
      suppression.

PMID- 15477636
TI  - Carboplatin in combination therapy for metastatic breast cancer.
AB  - BACKGROUND: Anthracycline-based regimens have a limited role in patients with
      metastatic breast cancer due to cumulative cardiotoxicity and their common use in
      adjuvant chemotherapy. New nonanthracycline regimens are, therefore, needed for
      metastatic disease. Single-agent carboplatin is active in patients with
      previously untreated metastatic breast cancer, producing response rates of 20%
      35%. Preclinical studies have demonstrated synergistic antitumor efficacy of
      carboplatin and trastuzumab in HER2(+) models. METHODS: Phase II and III clinical
      trial data of combination therapy with carboplatin (Paraplatin; Bristol-Myers
      Squibb; Princeton, NJ), a taxane, and/or trastuzumab (Herceptin; Genentech, Inc.;
      South San Francisco, CA) in metastatic breast cancer were identified from
      multiple sources, including: A) clinical trial data published in peer-reviewed
      journals within the last 5 years; B) preliminary clinical trial data from
      abstracts recently presented at national meetings; and C) phase III protocols
      currently evaluating carboplatin-based combination regimens. RESULTS: In several
      phase II studies, combination carboplatin and paclitaxel (Taxol; Bristol-Myers
      Squibb) therapy was active and reasonably well tolerated in the first-line
      treatment of metastatic breast cancer, producing objective response rates of 53%
      62%-substantially higher rates than those seen in other phase II trials of either
      drug alone. Similar phase II data for carboplatin with docetaxel (Taxotere;
      Aventis; Bridgewater, NJ) have been reported, and recent phase III data suggest
      that adding carboplatin to a paclitaxel/trastuzumab regimen produces superior
      efficacy than paclitaxel/trastuzumab alone for patients with HER2(+) metastatic
      disease. Drug scheduling plays an important role in the therapeutic ratio of this
      combination treatment. CONCLUSIONS: Incorporation of carboplatin as a standard
      agent in first-line treatment of metastatic breast cancer has support from
      several recent studies. Preliminary results of combination carboplatin/taxane
      therapy with trastuzumab in metastatic disease are encouraging, and other
      carboplatin combinations are also being investigated in other phase II and III
      trials in patients selected based on the HER2 status of their cancer. Results are
      eagerly awaited.

PMID- 15477637
TI  - Dynamic magnetic resonance perfusion imaging of brain tumors.
AB  - In this paper, we review the technique of contrast-enhanced magnetic resonance
      (MR) perfusion imaging of brain neoplasms, with an emphasis on its clinical
      applications and utility. We start with a discussion of MR perfusion techniques
      available today and their relative merits and shortcomings. Next, the ability of
      MR perfusion to provide a preoperative assessment of tumor histology is examined.
      We also discuss the role of MR perfusion in helping guide tumor biopsy, and its
      advantages over more conventional methods. We will scrutinize the use of MR
      perfusion for assessing true lesion extent, in contrast to conventional MR
      imaging and other MR techniques. We will discuss the role of MR perfusion in
      differentiating treatment effects, such as radiation necrosis, from tumor
      recurrence. Finally, the future potential applications of this technology in the
      setting of novel antiangiogenic therapies for brain tumors will be addressed.

PMID- 15477638
TI  - Practical aspects of weekly docetaxel administration schedules.
AB  - Docetaxel (Taxotere; Aventis Pharmaceuticals Inc.; Bridgewater, NJ) is a highly
      effective chemotherapeutic agent with proven efficacy in a number of solid
      tumors. However, myelosuppression can be a substantial concern when docetaxel is
      administered every 3 weeks. Myelosuppression can be particularly problematic in
      older patients and those being treated with palliative intent. Weekly dosing of
      docetaxel has been investigated in an effort to reduce toxicity and has been
      identified as a safe and effective regimen in clinical trials. Weekly docetaxel
      is generally administered at doses ranging from 30-40 mg/m(2)/week for 6 of 8
      weeks or for 3 of 4 weeks. With weekly dosing, though efficacy is comparable,
      myelosuppression is substantially less, and the overall tolerability profile is
      better than with every-3-week dosing. Fatigue is a common toxicity associated
      with weekly docetaxel; other adverse effects that are seen in a minority of
      patients include hyperlacrimation, nail toxicity, and alopecia. These side
      effects are dose related and can generally be managed through dose reductions or
      alterations in the weekly schedule. Because of the favorable tolerability
      profile, weekly docetaxel is under investigation in combination with other
      chemotherapeutic agents and with novel targeted agents in a variety of tumor
      types. The results of these ongoing studies will further define the place of
      weekly docetaxel in cancer therapy.

PMID- 15477639
TI  - Hypersensitivity reactions to oxaliplatin and the application of a
      desensitization protocol.
AB  - Oxaliplatin (Eloxatin; Sanofi-Synthelabo Inc.; New York, NY) is a third
      generation platinum agent indicated for the treatment of colorectal cancer.
      Severe hypersensitivity reactions to oxaliplatin rarely occur; however, they do
      represent a threat to the small number of patients that are occasionally
      affected. We developed a desensitization protocol and successfully applied it to
      a patient with severe, grade 3, hypersensitivity to oxaliplatin. For patients who
      have mild sensitivity to oxaliplatin, slowing the run rate down and giving an
      antihistamine and/or a steroid usually suffice. Desensitization will help to
      provide the small number of patients who experience severe hypersensitivity
      reactions with the ability to further receive an effective therapy for their
      colorectal cancer. The desensitization protocol is described in detail.

PMID- 15477640
TI  - Superior sulcus tumors: a mini-review.
AB  - The management and outcome for superior sulcus tumors have remained unchanged for
      40 years. The rarity of these tumors has led to varying treatment techniques
      spanning decades, from which no solid conclusions can be drawn. Recent advances
      in combined-modality therapy have offered the first inkling that a paradigm shift
      is on the horizon. Here, we review the history and new advances in treating this
      challenging pulmonary neoplasm.

PMID- 15477641
TI  - Non-small cell lung cancer in the elderly.
AB  - The population is aging both in developing and developed countries. What is clear
      is that currently over 50% of all patients with non-small cell lung cancer
      (NSCLC) are 65 years of age or older. When deciding a treatment strategy, the
      biological rather than the chronological age should be carefully assessed, and
      treatment should only be modified or withheld for very good reason. This applies
      equally to surgery, radiation therapy, and chemotherapy. Fortunately, recently
      published studies have focused on the issue and have provided strong evidence of
      improved progression-free survival, overall survival, and quality of life in
      elderly patients with appropriately treated NSCLC.

PMID- 15477642
TI  - Management of bleeding in patients with advanced cancer.
AB  - Bleeding occurs in up to 10% of patients with advanced cancer. It can present in
      many different ways. This article provides a qualitative review of treatment
      options available to manage visible bleeding. Local modalities, such as
      hemostatic agents and dressings, radiotherapy, endoscopic ligation and
      coagulation, and transcutaneous arterial embolization, are reviewed in the
      context of advanced cancer, as are systemic treatments such as vitamin K,
      vasopressin/desmopressin, octreotide/somatostatin, antifibrinolytic agents
      (tranexamic acid and aminocaproic acid), and blood products. Considerations at
      the end of life are described.

PMID- 15477643
TI  - Adjuvant analgesics in cancer pain management.
AB  - Adjuvant analgesics are defined as drugs with a primary indication other than
      pain that have analgesic properties in some painful conditions. The group
      includes numerous drugs in diverse classes. Although the widespread use of these
      drugs as first-line agents in chronic nonmalignant pain syndromes suggests that
      the term "adjuvant" is a misnomer, they usually are combined with a less-than
      satisfactory opioid regimen when administered for cancer pain. Some adjuvant
      analgesics are useful in several painful conditions and are described as
      multipurpose adjuvant analgesics (antidepressants, corticosteroids, alpha(2)
      adrenergic agonists, neuroleptics), whereas others are specific for neuropathic
      pain (anticonvulsants, local anesthetics, N-methyl-D-aspartate receptor
      antagonists), bone pain (calcitonin, bisphosphonates, radiopharmaceuticals),
      musculoskeletal pain (muscle relaxants), or pain from bowel obstruction
      (octreotide, anticholinergics). This article reviews the evidence supporting the
      use of each class of adjuvant analgesic for the treatment of pain in cancer
      patients and provides a comprehensive outline of dosing recommendations, side
      effects, and drug interactions.

PMID- 15477644
TI  - The molecular perspective: cyclins.

PMID- 15477645
TI  - Low-dose warfarin prophylaxis for catheter-associated thrombosis in cancer
      patients. Can it be safely associated with 5-Fluorouracil-based chemotherapy?

PMID- 15477647
TI  - Construction and characterization of a minimized version of the HIV-1 pNL4-3
      plasmid and its application for pseudotyping HIV-1 vectors.
AB  - The pUC-based pNL4-3 plasmid is the most widely used vector for in vitro
      manipulations of the HIV-1 proviral sequences. We have developed a minimal
      plasmid (pCHUS) based on pNL4-3, which may be useful to facilitate the design of
      HIV-based constructions. The strategy that has allowed us to construct pCHUS
      includes the following steps: (1) pNL4-3 digestion by using restriction sites
      contained within the long terminal repeats (LTRs), (2) recircularization of the
      fragment containing the pUC18 sequence, (3) amplification of the LTR region
      restored in the previous step, (4) double digestion of the products obtained in
      steps 2 and 3, (5) ligation of the fragment containing ColE1+Amp(R) with the LTR
      fragment, (6) linearization of the intermediate plasmid obtained, and (7)
      insertion of the fragment containing the proviral genome into the linearized
      vector. The pCHUS plasmid includes essential information for its replication and
      antibiotic selection in bacteria, but it lacks all the unnecessary sequences. Our
      results suggest that pCHUS may be more advantageous than pNL4-3 for in vitro
      manipulation of the HIV-1 proviral genome. In addition, we describe a potential
      application of this new vector for pseudotyping HIV-1 particles, using a single
      plasmid transfection, as a more helpful alternative to the traditionally used
      cotransfection method.

PMID- 15477648
TI  - Metafectene is superior to lipofectamine in the transfection of G(s) alpha
      prostate cancer cells.
AB  - Transfection efficiency of the novel reagent metafectene has not been compared
      with that of lipofectamine in the published English literature. We used these
      agents to transfect two prostate cancer cell lines, PC3 and G(s) alpha, with a
      deoxyribonucleic acid (DNA) expression vector that generates double-stranded
      ribonucleic acid (RNA) for RNA interference (RNAi). Cotransfection of the green
      fluorescent protein (GFP) reporter gene revealed that the mean (+/- standard
      deviation) transfection efficiencies with lipofectamine were 5.8+/-0.4% for PC3
      cells and 3.6+/-1.5% for G(s) alpha cells. Mean transfection efficiency with
      metafectene declined to 0.1+/-0% for PC3 cells but improved to 54.6+/-5.5% for
      G(s) alpha cells. With G(s) alpha cells, metafectene transfection of GFP plasmid
      alone yielded 46.9% positive cells, and cotransfection with CD44v9 expression
      vector yielded 45.9% positive cells. The visual impact of the transfected RNAi
      construct was detectable at the protein level 4 to 6 d posttransfection and was
      more dramatic after using metafectene than after using lipofectamine. Thus, in
      vitro, metafectene transfection efficiency was sufficient to allow us to assess
      the functional significance of our RNAi construct, suggesting metafectene as an
      excellent candidate for RNAi-mediated anticancer gene therapy.

PMID- 15477649
TI  - Expression of a functional single-chain Fv antibody on the surface of
      Streptococcus gordonii.
AB  - Gram-positive bacterium Streptococcus gordonii, a human oral commensal, was
      engineered to display a single-chain Fv (scFv) antibody fragment at the cell
      surface. The previously developed host-vector system allowed expression of the
      Guy's 13 scFv as a fusion with the streptococcal surface protein M6. Surface
      expression of the 515-amino acid M6/scFv fusion protein was confirmed by Western
      blot analysis on cellular fractions and flow cytometric analysis. Guy's 13 scFv
      was derived from the Guy's 13 monoclonal antibody, which was raised against
      streptococcal antigen I/II (SA I/II), the major adhesin of the caries-producing
      bacterium Streptococcus mutans. Surface plasmon resonance was used to test
      binding of scFv-expressing S. gordonii to SA I/II. Whole cells of recombinant S.
      gordonii were found to specifically bind to immobilised SA I/II and binding was
      inhibited by fluid-phase SA I/II in a dose-dependent manner. Production of a
      functional scFv in S. gordonii is the first step towards the development of
      genetically engineered commensal bacteria that, by colonizing mucosal surfaces,
      may provide the host with sustained delivery of recombinant antibodies.

PMID- 15477650
TI  - A rapid and highly efficient method for transformation of sugarcane callus.
AB  - Modern sugarcane cultivars have complex genetic characteristics and low fertility
      that render their genetic improvement through traditional breeding difficult.
      Genetic engineering methodology to introduce foreign genes provides new
      opportunities for the genetic improvement of sugarcane cultivars. One of
      prerequisites for successful insertion of a gene cassette into the plant genome
      is the availability of an efficient transformation protocol. An improved protocol
      for Agrobacterium-mediated transformation of sugarcane is described. Between 85
      and 100% of calli transformed using this procedure produced new calli, and 100%
      of them were positive for the inserted gene. The whole procedure permitted the
      production of transgenic calli in a short time (1.5 mo). The transformed calli
      can be cultured further for the production of the inserted gene-encoded enzyme by
      using cell culture, or they can be regenerated into transgenic plants. This
      protocol may be implemented also for the generation of transgenic plants from
      other species.

PMID- 15477651
TI  - Low-volume jet injection for efficient nonviral in vivo gene transfer.
AB  - The transfer of naked deoxyribonucleic acid (DNA) represents an alternative to
      viral and liposomal gene transfer technologies for gene therapy applications.
      Various procedures are employed to deliver naked DNA into the desired cells or
      tissues in vitro and in vivo, such as by simple needle injection, particle
      bombardment, in vivo electroporation or jet injection. Among the various nonviral
      gene delivery technologies jet injection is gaining increasing acceptance because
      it allows gene transfer into different tissues with deeper penetration of the
      applied naked DNA. The versatile hand-held Swiss jet injector uses pressurized
      air to force small volumes of 3 to 10 microL of naked DNA into targeted tissues.
      The beta-galactosidase (LacZ) reporter gene construct and tumor necrosis factor
      alpha gene-expressing vectors were successfully jet injected at a pressure of 3.0
      bar into xenotransplanted human tumor models of colon carcinoma. Qualitative and
      quantitative expression analysis of jet injected tumor tissues revealed the
      efficient expression of these genes in the tumors. Using this Swiss jet-injector
      prototype repeated jet injections of low volumes (3-10 microL) into one target
      tissue can easily be performed. The key parameters of in vivo jet injection such
      as jet injection volume, pressure, jet penetration into the tumor tissue, DNA
      stability have been defined for optimized nonviral gene therapy. These studies
      demonstrate the applicability of the jet injection technology for the efficient
      and simultaneous in vivo gene transfer of two different plasmid DNAs into tumors.
      It can be employed for nonviral gene therapy of cancer using minimal amounts of
      naked DNA.

PMID- 15477652
TI  - Pyrosequencing: sequence typing at the speed of light.
AB  - Nucleotide sequencing is an established method for gaining information relating
      to partial gene, whole gene, or whole genome sequence. Here we describe some of
      the background leading to the advent of modern nucleotide sequencing and how it
      has led to the development of Pyrosequencing, a relatively new method for real
      time nucleotide sequencing. In particular, we describe how this method can be
      used for typing bacterial pathogens.

PMID- 15477653
TI  - Genotypic characterization of Neisseria meningitidis using Pyrosequencing.
AB  - Pyrosequencing involves the synthesis of single-stranded deoxyribonucleic acid
      leading to rapid and accurate analysis of nucleotide sequences. This article
      describes the development of typing assays for the characterization of Neisseria
      meningitidis using Pyrosequencing. This involved developing methods for the
      nucleotide sequence analysis of important variable regions contained on a major
      capsule gene and on outer membrane protein genes that are used for grouping,
      typing, and subtyping meningococci. To achieve this, primers were designed for
      amplification of three genes, siaD, porB, and porA from the four main serogroups
      B, C, Y, and W135. To facilitate throughput and reproducibility, the method was
      also automated. Data from 717 isolates have shown that Pyrosequencing can be used
      for the single nucleotide polymorphism and sequence-analysis characterization of
      meningococci.

PMID- 15477655
TI  - MHC class II gene expression is not induced in HPIV3-infected respiratory
      epithelial cells.
AB  - The major histocompatibility complex (MHC) class II transactivator (CIITA)
      typically is required for both constitutive and inducible expression of MHC class
      II genes. However, transcription of class II MHC genes has been observed in
      specific cell types (e.g., thymic epithelial cells) in CIITA-deficient mice as
      well as in specific situations (e.g., following viral infections or in natural
      killer [NK]/target cell interaction). These observations have been interpreted by
      some to indicate that a CIITA-independent pathway of class II gene expression
      might be germane to processes such as the acquisition of tolerance during thymic
      selection or in the evasion of immune surveillance by a subset of viruses. One of
      the most striking examples of CIITA-independent, inducible class II gene
      expression has involved the de novo expression of class II MHC molecules on
      respiratory epithelial cells following infection by human parainfluenza virus
      type 3 (HPIV3). We report here that despite careful analysis using multiple
      techniques, we have been unable to detect HPIV3-dependent, CIITA-independent (or
      CIITA-dependent) induction of class II MHC genes. Thus, whereas there may still
      be an intriguing role for CIITA-independent gene expression in facets of the
      immune response, this is unlikely to manifest in the analysis of HPIV3 infection
      of respiratory epithelial cells.

PMID- 15477654
TI  - Wound-healing studies in transgenic and knockout mice.
AB  - Injury to the skin initiates a cascade of events including inflammation, new
      tissue formation, and tissue remodeling, that finally lead to at least partial
      reconstruction of the original tissue. Historically, animal models of repair have
      taught us much about how this repair process is orchestrated and, over recent
      years, the use of genetically modified mice has helped define the roles of many
      key molecules. Aside from conventional knockout technology, many ingenious
      approaches have been adopted, allowing researchers to circumvent such problems as
      embryonic lethality, or to affect gene function in a tissue- or temporal-specific
      manner. Together, these studies provide us with a growing source of information
      describing, to date, the in vivo function of nearly 100 proteins in the context
      of wound repair. This article focuses on the studies in which genetically
      modified mouse models have helped elucidate the roles that many soluble mediators
      play during wound repair, encompassing the fibroblast growth factor (FGF) and
      transforming growth factor-beta (TGF-beta) families and also data on cytokines
      and chemokines. Finally, we include a table summarizing all of the currently
      published data in this rapidly growing field. For a regularly updated web archive
      of studies, we have constructed a Compendium of Published Wound Healing Studies
      on Genetically Modified Mice which is avaialble at
      http://icbxs.ethz.ch/members/grose/woundtransgenic/home.html.

PMID- 15477656
TI  - Regulation of immune responses by CD1d-restricted natural killer T cells.
AB  - Natural killer T (NKT) cells are a unique subset of T lymphocytes that share
      receptor structures and properties with conventional T lymphocytes and natural
      killer (NK) cells. NKT cells are specific for glycolipid antigens such as the
      marine sponge-derived agent alpha-galactosylceramide (alpha-GalCer) presented by
      the major histocompatibility complex (MHC) class I-like molecule CD1d. My
      laboratory has evaluated the function of NKT cells by generating and analyzing
      CD1d-deficient mice. These studies showed that CD1d expression is required for
      NKT cell development, but not absolutely necessary for the generation of
      polarized T helper (Th) cell responses. Further, we have studied the in vivo
      response of NKT cells to alpha-GalCer stimulation and the capacity of alpha
      GalCer to modulate innate and adaptive immune responses. Our results revealed
      that, quickly following administration of alpha-GalCer, NKT cells expand and
      produce cytokines, trans-activate a variety of innate and adaptive immune cells,
      and promote Th2 responses that are capable of suppressing Th1-dominant
      autoimmunity. Our findings indicate that NKT cells play a regulatory role in the
      immune response and that specific activation of these cells may be exploited for
      therapeutic purposes.

PMID- 15477657
TI  - Tolerogenic antigen-presenting cells: regulation of the immune response by TGF
      beta-treated antigen-presenting cells.
AB  - Tolerogenic antigen-presenting cells (APCs) are attractive agents for the
      treatment of autoimmune and inflammatory diseases that are mediated, at least in
      part, by antigen-specific autoreactive T cells. Transforming growth factor-beta
      (TGF-beta)-treated antigen-presenting cells induce a very potent form of
      tolerance in mice. One unique feature of this simple and elegant method of
      tolerance induction is that it is equally potent in both primed and naive mice,
      an important consideration for the development of a therapy that will be
      effective against an established disease. In this model, F4/80+ peritoneal
      exudate cells (macrophages) cultured with antigen and TGF-beta2 injected iv
      induce populations of regulatory T cells that mediate long-lasting antigen
      specific tolerance in mice. The mechanisms that are involved in the induction of
      tolerance by TGF-beta-treated APCs are very complex and require the interaction
      of a variety of cell types, as well as soluble and membrane-bound factors. In
      this review, we summarize the existing data and present new data concerning the
      induction and effector mechanisms associated with TGF-beta-treated APC-induced
      tolerance. An understanding of these mechanisms will provide very important
      information for the design of effective strategies for the treatment of a variety
      of diseases that are mediated by pathogenic T cells.

PMID- 15477658
TI  - Association of intracellular proteins with folded major histocompatibility
      complex class I molecules.
AB  - The major histocompatibility complex (MHC) class I molecule is responsible for
      presenting peptide antigens at the cell surface for recognition by cytotoxic T
      lymphocytes. Several chaperone molecules interact with the MHC class I heavy
      chain and release when the MHC groove folds around peptide. Two additional
      proteins, invariant chain and amyloid precursor-like protein 2 (APLP2), interact
      specifically and stably with MHC class I molecules that have folded peptide
      binding grooves. Invariant chain and APLP2 also affect MHC class I cell-surface
      expression, and so may play a part in MHC class I trafficking. Association of
      APLP2 with the MHC class I molecule appears to be regulated by a viral protein,
      the adenovirus E3/19K protein. Analysis of the interactions of these proteins
      with each other and with MHC class I will clarify how presentation of antigens by
      MHC class I is controlled by events that occur subsequent to MHC class I folding.

PMID- 15477659
TI  - Cytokine polymorphism and its possible impact on cancer.
AB  - Human cancer is an unpredictable disease as is its response to therapy. The
      intrinsic genetic heterogeneity and instability of cancer cells could in part
      explain such behavior. However, it is possible that, individual variation in the
      genetic make-up of humans may affect the relationship between host and cancer
      cells and, therefore, be, at least in part responsible for this extraordinary
      variation. Human gene polymorphism has been shown indeed to play a role in immune
      responses; among the immune-related genes, cytokines are often polymorphic. Some
      polymorphisms of cytokine and cytokine receptor may have direct functional
      significance by altering directly and indirectly the level of gene expression
      and/or its function; other may only demarcate a genetic linkage to a particular
      haplotype associated with a given clinical condition. The majority of
      polymorphisms found in cytokines or their receptors are located in the promoter,
      intronic and 3' untranslated regions. These sequence variations can still affect
      gene expression and function. In this review will we summarize the current
      knowledge about the role of cytokine polymorphism in disease and more
      specifically in cancer.

PMID- 15477660
TI  - Consequences of CXCL10 and IL-6 induction by the murine IFN-alpha1 transgene in
      ocular herpes simplex virus type 1 infection.
AB  - Herpes simplex virus type 1 infection of the mouse eye results in an impressive
      inflammatory response culminating in the death of the animal or the establishment
      of a "latent" infection depending on a number of ill-defined variables that
      include components of the innate and adaptive immune system. The application of
      type I interferon transgenes has been found to antagonize viral replication and
      spread from the eye to the nervous system. Associated with the in situ
      transfection of the cornea is the upregulation of two inflammatory molecules,
      interleukin-6 and CXCL10. In this article, we will further examine the
      contribution these molecules may have in the host response to ocular infection
      with herpes simplex virus type 1.

PMID- 15477661
TI  - The role of LIGHT in T cell-mediated immunity.
AB  - This review focuses on the role of homologous to lymphotoxin, exhibits inducible
      expression, competes with herpesvirus glycoprotein D for HVEM on T cells (LIGHT)
      in T-cell immunity and T cell-mediated diseases. LIGHT binds to lymphotoxin-beta
      receptor (LTbetaR), and cooperates with LTbeta in lymphoid organogenesis and
      development of lymphoid structure. Previous findings establish a crucial
      biological role for LIGHT, a T cell-derived costimulatory ligand, in T-cell
      activation and expansion via a T-T cell-dependent manner. Transgenic studies
      demonstrated that the dysregulation of LIGHT activity results in the disturbance
      of T-cell homeostasis and ultimately the breakdown of peripheral tolerance.
      Furthermore, the blockade of LIGHT activity ameliorates the severity of T cell
      mediated diseases indicating the essential involvement of LIGHT in various
      pathological conditions. Here, we review the recent studies about LIGHT mainly in
      the context of autoimmunity and conclude with a discussion of the potential
      mechanisms by which LIGHT promotes autoimmunity.

PMID- 15477662
TI  - Induction of RNA interference in dendritic cells.
AB  - Dendritic cells (DC) reside at the center of the immunological universe,
      possessing the ability both to stimulate and inhibit various types of responses.
      Tolerogenic/regulatory DC with therapeutic properties can be generated through
      various means of manipulations in vitro and in vivo. Here we describe several
      attractive strategies for manipulation of DC using the novel technique of RNA
      interference (RNAi). Additionally, we overview some of our data regarding yet
      undescribed characteristics of RNAi in DC such as specific transfection
      strategies, persistence of gene silencing, and multi-gene silencing. The
      advantages of using RNAi for DC genetic manipulation gives rise to the promise of
      generating tailor-made DC that can be used effectively to treat a variety of
      immunologically mediated diseases.

PMID- 15477663
TI  - Multiple T-cell clones specific for the same foreign pMHC ligand can be generated
      from a single, ancestral TCR-VDJbeta precursor.
AB  - Owing to ordered, stage-specific T-cell receptor (TCR) gene rearrangements and
      cell division during T-cell development, small cohorts of "half-sibling" T cells
      sharing an ancestral TCR VDJbeta rearrangement but expressing different TCR alpha
      locus rearrangements may be selected into the mature T-cell repertoire. We
      wondered whether different alphabetaTCRs expressed by T cells from the same
      ancestral VDJbeta cohort might be capable of recognizing the same foreign peptide
      major histocompatibility complex complex (pMHC). By a combined flow cytometric
      and single-cell polymerase chain reaction (PCR) approach to analyze TCRs selected
      by the previously defined foreign antigen, pCW3170-179/H-2Kd, we were able to
      identify cohorts of half-sibling antigen-specific CD8 T cells after their
      expansion in immunized mice. We amplified residual DJbeta rearrangements as
      clonal markers to confirm that the shared VDJbeta sequences represent ancestral
      rearrangements rather than identical but independent ones. An intriguing
      explanation of our findings would be that only a very limited repertoire of TCR
      alpha-chains is selected to pair with a given TCR beta-chain during T-cell
      development.

PMID- 15477665
TI  - Re: Immunologic Research review (Zheng S-J and Chen YH. TRAIL, Bim, and Thymic
      Negative Selection. Immunol. Res. 2003; 28/3:295-301).

PMID- 15477667
TI  - Magnetizable needles and wires--modeling an efficient way to target magnetic
      microspheres in vivo.
AB  - The in vivo targeting of tumors with magnetic microspheres is currently realized
      through the application of external non-uniform magnetic fields generated by rare
      earth permanent magnets or electromagnets. Our theoretical work suggests a
      feasible procedure for local delivery of magnetic nano- and microparticles to a
      target area. In particular, thin magnetizable wires placed throughout or close to
      the target area and magnetized by a perpendicular external uniform background
      magnetic field are used to concentrate magnetic microspheres injected into the
      target organ's natural blood supply. The capture of the magnetic particles and
      the building of deposits thereof in the blood vessels of the target area were
      modeled under circumstances similar to the in vivo situation. This technique
      could be applied to magnetically targeted cancer therapy or magnetic embolization
      therapy with magnetic particles that contain anticancer agents, such as
      chemotherapeutic drugs or therapeutic radioisotopes.

PMID- 15477664
TI  - Rethinking the role of Src family protein tyrosine kinases in the allergic
      response: new insights on the functional coupling of the high affinity IgE
      receptor.
AB  - Antigen-induced cross-linking of immunoglobulin E (IgE) antibodies bound to the
      high-affinity IgE receptor (FcepsilonRI), on mast cells results in the release of
      mediators that initiate an inflammatory response. This normal immune response has
      been abducted by immunological adaptation, through the production of IgE
      antibodies to normally innocuous substances, to cause allergic disease.
      Therefore, understanding the molecular requirements in IgE-dependent mast-cell
      activation holds promise for therapeutic intervention in disease. Recent
      investigation on the functional coupling of FcepsilonRI to the intracellular
      signaling apparatus has provided paradigm-altering insights on the importance and
      function of Src family protein tyrosine kinases (Src PTK) in mast-cell
      activation. In this synopsis, we review the current knowledge on the role of the
      Src PTKs, Fyn and Lyn, in mast-cell activation and discuss the implications of
      our findings on allergic disease.

PMID- 15477668
TI  - Tenocyte response to cyclical strain and transforming growth factor beta is
      dependent upon age and site of origin.
AB  - The effect of strain and transforming growth factor beta on equine tendon
      fibroblasts (tenocytes) was assessed in vitro. Tenocytes were isolated from
      flexor and extensor tendons of horses from foetal to 10 years of age. These cells
      were cultured until confluent on collagen-coated silicone dishes. Cyclic biaxial
      strain of 9+/-1% was applied at 0.5 Hz for 24 hours with or without added
      TGFbeta1 or 3 (10 ng/ml). Proliferation and synthetic responses were dependent on
      the tendon of origin. Neither strain nor TGFbeta caused flexor tenocytes to
      proliferate significantly, while strain alone did proliferate extensor tenocytes.
      TGFbeta, with or without strain, increased the incorporation of [3H]-proline and
      the production of types I and III collagen and COMP in both cell types, although
      the effect on COMP production was more marked in flexor tenocytes, perhaps
      reflecting the higher levels found in this tendon in vivo. Immature flexor
      tenocytes synthesised more collagen and COMP than those from mature animals,
      while age had little effect in extensor tenocytes. Our results suggest that
      tenocytes become differentiated at an early age and present tendon-specific
      responses.

PMID- 15477669
TI  - Quantitative analysis of the effects of hyaluronan and aggrecan concentration and
      hyaluronan size on the elasticity of hyaluronan-aggrecan solutions.
AB  - We determined elasticity (G') and viscosity (G'') of various aggrecan-hyaluronan
      solutions using a controlled-stress rheometer with high (10 Hz) to low (0.1 Hz)
      frequencies. Aggrecan solution (50 mg/ml) alone showed little elasticity at any
      frequency, but the addition of 3300 kDa hyaluronan at 0.001-0.1 mg/ml markedly
      increased the elasticity, but not the viscosity, at all frequencies. Increasing
      hyaluronan concentration at >0.1 mg/ml did not further increase the elasticity of
      the aggrecan solution, and the elasticity of the aggrecan-hyaluronan complex
      solution reached a plateau at a 500:1 (w/w) ratio. In studies with increasing
      concentrations of aggrecan and a constant concentration (0.5 mg/ml) of 3300 kDa
      hyaluronan, aggrecan induced elasticity only at >20 mg/ml, indicating the
      presence of a critical concentration for elasticity. In the presence of 50 mg/ml
      aggrecan, 1000 kDa hyaluronan had far less effect on the elasticity of the
      aggrecan solution than did 3300 kDa hyaluronan. These findings suggest that only
      approximately 50% reduction in aggrecan concentration (<20 mg/ml), or reduced
      hyaluronan size (<1000 kDa)--compared with their physiological levels in young
      cartilage--can abolish the elastic network of the aggrecan-hyaluronan complex.

PMID- 15477670
TI  - The effects of margination and red cell augmented platelet diffusivity on
      platelet adhesion in complex flow.
AB  - The effects of platelet margination and enhanced platelet diffusivity, as induced
      by red blood cells, on the adhesion of platelets, were investigated for a range
      of haematocrits, under 2D axi-symmetric flow, simulating previous in vitro
      experiments [Microvasc. Res. 17 (1979), 238-262]. The effect of margination was
      incorporated via use of an elevated platelet inlet mass fraction, Phie, in a
      manner similar to that of Wootton [Ann. Biomed. Eng. 29 (2001), 321-329], and a
      shear and haematocrit dependent platelet diffusivity, according to the model
      presented by Zydney and Colton [Physico Chem. Hydrodyn. 10 (1988), 77-96] was
      used. A combination of the two models was required to simulate the deposition of
      platelets to a collagen coated surface, under the complex flow, which exhibited a
      recirculation zone and stagnation point. Results obtained showed qualitative
      agreement with in vitro results, for a range of haematocrits (11-50%), and also
      showed that the effects of margination were not linearly dependent on
      haematocrit. Agreement may be improved in future simulations by incorporating the
      effects of depleted cell concentrations in the vortex which have been observed
      previously [Phil. Trans. Roy. Soc. (Lond.) B279 (1977), 413-445]. It would also
      be advantageous to devise a full mathematical description for platelet
      margination effects as a function of shear rate and haematocrit and a description
      of the accompanying effect of apparent blood viscosity.

PMID- 15477671
TI  - Effect of steady and oscillatory shear stress on F-actin content and distribution
      in neutrophils.
AB  - We investigated neutrophil activation, specifically F-actin content and
      distribution, in situations mimicking the in vivo environment using steady and
      oscillatory shear. Under low steady shear (<150 s(-1)) F-actin levels were
      decreased for both treated (n-formyl-L-methioryl-L-leucyl-L-phenylalanine (fMLP))
      and untreated neutrophils. The F-actin content increased with a change to higher
      steady shear levels. Neutrophils show the same behavior of decreased F-actin
      content for oscillatory shear (26.7 s(-1)) as they did for steady shear. In both
      situations, the low shear levels caused a decrease in F-actin content. However,
      as the magnitude of the shear rate increased, cells showed a reversal to
      increasing F-actin content. Shear caused a decrease in F-actin in the cell cortex
      for both control and fMLP treated cells. Ctyochalasin B (CB), a common F-actin
      assembly blocker, significantly decreased F-actin content. The results indicate
      that neutrophils regulate their actin network based on the level and type of
      shear stress they encounter in the bloodstream.

PMID- 15477672
TI  - The interplay between experiment and theory in charge-density analysis.
AB  - The comparison of theory and experiment remains a cornerstone of scientific
      inquiry. Various levels of such comparison applicable to charge-density analysis
      are discussed, including static and dynamic electron densities, topological
      properties, d-orbital occupancies and electrostatic moments. The advantages and
      drawbacks of the pseudoatom multipole are discussed, as are the experimentally
      constrained wavefunctions introduced by Jayatilaka and co-workers, which combine
      energy minimization with the requirement to provide a reasonable fit to the X-ray
      structure factors. The transferability of atomic densities can be exploited
      through construction of a pseudoatom databank, which may be based on analysis of
      ab initio molecular electron densities, and can be used to evaluate a host of
      physical properties. Partitioning of theoretical energies with the Morokuma
      Ziegler energy decomposition scheme allows direct comparison with electrostatic
      interaction energies obtained from electron densities represented by the
      pseudoatom formalism. Compared with the Buckingham expression for the interaction
      between non-overlapping densities, the agreement with theory is much improved
      when a newly developed hybrid EP/MM (exact potential/multipole model) method is
      employed.

PMID- 15477673
TI  - On the role of data quality in experimental charge-density studies.
AB  - High-resolution X-ray diffraction data were collected at T = 19 K from two
      similar spherical crystals of the fungal metabolite citrinin, C(13)H(14)O(5). The
      two data sets were of markedly different quality, one data set (MQ, medium
      quality) comprising a single octant of the reciprocal lattice and including
      reflections with obviously peculiar intensity profiles while the second (HQ, high
      quality) comprised a hemisphere of reflections and showed no flawed profiles.
      Parallel multipolar refinements were carried out for both. While most of the
      resulting geometric parameters, including bond lengths and angles, were in close
      agreement (the standard uncertainties were approximately twice as large for the
      MQ data, reflecting the smaller number of observations), the agreement is
      noticeably worse for electronic properties such as electron densities and their
      Laplacians at the bond and ring critical points. These latter features are
      especially sensitive to the quality of the low-angle (and strong) intensities,
      which was not high for the MQ data. By contrast, the magnitudes of the molecular
      dipole moment from the two experiments are the same within 1 standard
      uncertainty, with an angle of about 13 degrees between the two vectors. It is
      concluded that only true high-quality data allow a fully significant and
      quantitative analysis of the details of the experimental electron density
      rho(exp), while high-resolution medium-quality data, measured at very low
      temperature and adequately processed, can still be used for a qualitative
      analysis, or for the derivation of overall electronic properties.

PMID- 15477674
TI  - The charge density of urea from synchrotron diffraction data.
AB  - The charge density of urea is studied using very high precision single-crystal
      synchrotron-radiation diffraction data collected at the Swiss-Norwegian Beam
      Lines at ESRF. An unprecedented resolution of 1.44 A(-1) in sin theta;/lambda is
      obtained at 123 K. The optimization of the experiment for charge-density studies
      is discussed. The high precision of the data allowed the refinement of a
      multipole model extending to hexadecapoles and quadrupoles on the heavy and H
      atoms, respectively, as well as a liberal treatment of radial functions. The
      topological properties of the resulting electron density are analysed and
      compared with earlier experimental results as well as with periodic Hartree-Fock
      calculations. The properties of the strongly polarized C-O bond agree with trends
      derived from previous experimental results while the ab initio calculations
      differ significantly. The results indicate that the description of the C-O bond
      requires more flexible basis sets in the theoretical calculations. The calculated
      integrated atomic charges are much larger than the observed ones. It is suggested
      that the present experimental results provide new target values for validation of
      future ab initio calculations. The molecular dipole moment derived from the
      integrated atomic properties is the same as the one obtained from the multipole
      model even though the individual atomic contributions differ. Comparison with
      literature data for urea in solution and the gas phase yields a dipole
      enhancement in the solid of about 1.5 D. The thermal expansion of urea is
      determined using synchrotron powder diffraction data. With decreasing
      temperature, an increasing anisotropic strain is observed.

PMID- 15477675
TI  - Synchrotron charge-density studies in materials chemistry: 16 K X-ray charge
      density of a new magnetic metal-organic framework material,
      [Mn2(C8H4O4)2(C3H7NO)2].
AB  - A new magnetic metal-organic framework material,
      [Mn(2)(C(8)OH(4)(4))(2)(C(3)H(7)NO)(2)], has been synthesized. The structure
      consists of chains of carboxylate-bridged Mn atoms interconnected with acid
      linkers, giving much larger interchain than intrachain Mn...Mn distances.
      Magnetic susceptibility data fitted to a Curie-Weiss law give Theta = -5.7 K and
      a total magnetic moment of 5.96 micro(B). The heat capacity provides no evidence
      of magnetic ordering down to 2 K. The X-ray charge density was determined from
      multipole modeling of 16 (1) K single-crystal synchrotron-radiation data. The
      structural surroundings of the two unique Mn centers are different, but orbital
      population analysis reveals close to single electron occupation in all 3d
      orbitals of both Mn sites, in agreement with the magnetic susceptibility
      measurements. Bader topological analysis shows the presence of direct chemical
      Mn...Mn interactions only in two out of three intrachain contacts, which suggests
      a 'broken' chain. The topological measures and approximate energy densities at
      the metal-ligand bond critical points (rho, nabla(2)rho, G, V and H) indicate
      ionic interactions. Formal electron counting suggests mixed-valence Mn sites, but
      this hypothesis is not supported by the Bader atomic charges [q(Mn) = +2.035 and
      +2.031].

PMID- 15477677
TI  - Electron densities in relation to magnetism: gamma-ray diffraction from
      transition-metal monoxides and difluorides.
AB  - In this article, results are described from an area of solid-state physics that
      heretofore has remained unexplored by Bragg charge-scattering experiments. It is
      shown that gamma-ray electron densities can provide detailed information on
      magnetic ground-state properties at a subatomic resolution. The use of 316 keV
      gamma radiation has allowed low-order structure factors at better than 0.1%
      accuracy to be determined and, at the same time, extended data sets to be
      collected up to high momentum transfer. Prototypic antiferromagnets such as the
      late 3d transition-metal monoxides and difluorides have been systematically
      investigated, in most cases both in the paramagnetic and in the fully ordered
      phase. At transitions with a lowering of symmetry, multidomain formation was
      suppressed by application of external mechanical stress or magnetic fields. The
      results are considered in the context of information provided by recent magnetic
      neutron and X-ray studies.

PMID- 15477676
TI  - High-resolution synchrotron data collection for charge-density work at 100 and 20
      K.
AB  - For the measurement of very accurate high-resolution X-ray data for charge
      density work, synchrotron beamlines provide a bright radiation source of
      outstanding properties. Most important are the very high primary intensity and
      the possibility of choosing hard radiation with lambda approximately 0.5 A or
      even shorter. This together with area detection and a stable low-temperature
      device means that accurate and large data sets can be measured in a short time. A
      number of data collections are reported, which were carried out at the beamlines
      F1 and D3 of Hasylab (DESY, Hamburg) first at 100 K and later at 15-20 K,
      demonstrating the quality of the measured intensities. A low temperature of
      around 20 K was obtained at beamline D3 with a double-stage closed-cycle helium
      cryostat where the standard beryllium cylinder of the vacuum chamber was replaced
      by a 0.1 mm Kapton film. Comparison of different data sets measured for a
      strychnine crystal demonstrated how I/sigma ratios favorably improve if
      synchrotron radiation at a low temperature of 15 K was used. Synchrotron-based
      studies on several biologically active compounds are briefly summarized and a
      synchrotron experiment of an otherwise not sufficiently diffracting crystal of a
      tetraphenyl barbaralane derivative is described in detail. Atomic volumes and
      charges of a highly substituted C(60) fullerene are reported derived from a
      synchrotron data set of more than 350000 reflections.

PMID- 15477678
TI  - Extinction-free electron diffraction refinement of bonding in SrTiO3.
AB  - Accurate low-order Fourier coefficients of the crystal potential of SrTiO(3) are
      measured by quantitative convergent-beam electron diffraction. The accuracy in
      the corresponding derived X-ray structure factors is about 0.1% for the strong
      low-order reflections (sin theta/lambda < 0.3 A(-1)). This accuracy is better
      than for conventional X-ray diffraction and equivalent to the accuracy of the X
      ray Pendellosung method. Combination of these structure factors with high-order X
      ray diffraction measurements allows accurate bonding information to be obtained
      from a multipole model fitted to the experimental data. It is shown that Ti-O has
      a covalent component and that the Sr-O bond is mainly ionic. The role of Ti 3d
      electrons in Ti-O bonding is also discussed.

PMID- 15477679
TI  - Shadowing and absorption corrections of high-pressure powder diffraction data:
      toward accurate electron-density determinations.
AB  - The shadowing of the primary beam and of reflections from a powder crystal sample
      enclosed in a diamond-anvil high-pressure cell (DAC) is described for
      unrestricted data-collection procedures. The corrections account for the
      shadowing of the data measured with point- or area-detector diffractometers and
      can be applied for any containers of environment devices enclosing a powdered
      sample. The general procedure for correcting the powder diffraction data can be
      applied for analysing and optimizing diffractometric procedures of data
      collection and provides facilities for collecting high-pressure powder
      diffraction data with the DAC positioned optimally and rotated to counteract the
      preferred-orientation and particle-size effects, and to increase the resolution
      of data. The quadrature effects of numerical integration for the accuracy of
      computed corrections have been analysed.

PMID- 15477680
TI  - On functions and quantities derived from the experimental electron density.
AB  - Calculation of properties of molecules and crystals as obtained from a multipole
      electron-density model restored from the accurate X-ray diffraction data is
      considered. Electronic and exchange energy-density distributions are presented
      along with those of local temperature and local entropy. Integration of the local
      functions over atomic basins defined by the zero-flux condition allows properties
      of molecules and crystals to be expressed in terms of atomic contributions
      derived directly from X-ray diffraction experiments. Distributions of local Fermi
      momentum and one-electron potential are considered as well. The approach has been
      applied to diamond, sodium fluoride, sodium chloride, solid chlorine, alpha
      oxalic acid dihydrate and YBa(2)Cu(3)O(6.98).

PMID- 15477681
TI  - The quantum topological electrostatic potential as a probe for functional group
      transferability.
AB  - The electrostatic potential can be used as an appropriate and convenient
      indicator of how transferable an atom or functional group is between two
      molecules. Quantum-chemical topology (QCT) is used to define the electron density
      of a molecular fragment and the electrostatic potential it generates. The
      potential generated on a grid by the terminal aldehyde group of the biomolecule
      retinal is compared with the corresponding aldehyde group in smaller molecules
      derived from retinal. The terminal amino group in the free amino acid lysine was
      treated in a similar fashion. Each molecule is geometry-optimized by an ab initio
      calculation at B3LYP/6-311G+(2d,p)//HF/6-31G(d) level. The amino group in lysine
      is very little influenced by any part of the molecule further than two C atoms
      away. However, the aldehyde group in retinal is influenced by molecular fragments
      six C atoms away. This dramatic disparity is ascribed to the difference in
      saturation in the carbon chains; retinal contains a conjugated hydrocarbon chain
      but lysine an aliphatic one.

PMID- 15477682
TI  - Topological properties of the electron density of solids and molecules. Recent
      developments in Oviedo.
AB  - Some of the latest advances in the analysis of electron density are reviewed,
      including: (a) topological indices that provide a useful characterization of the
      global properties of the density; (b) specific results on some prototypical metal
      and low heteropolarity systems; and (c) calculation of the local curvature of the
      interatomic surface.

PMID- 15477683
TI  - The local form of the source function as a fingerprint of strong and weak intra-
      and intermolecular interactions.
AB  - This work introduces a local form for the source function, from each atom, for
      the electron-density value at a given point. The source function enables one to
      equate the value of the electron density at any point within a molecule to a sum
      of atomic contributions and thus to view properties of the density at
      representative points, such as the bond critical points, from a new perspective.
      The local form of the function introduces further detail. When plotted along a
      bond path and with reference to the bond critical point (b.c.p.), the source
      function shows which regions of the atoms involved in the bonding are
      accumulating or removing electronic charge at the b.c.p. The local form of the
      source function therefore represents an interesting fingerprint of a given
      bonding interaction. The local source may be expressed as a sum of two
      contributions, related to the kinetic energy density and electronic potential
      energy density, respectively. This approach gives further physical insight into
      why an atomic region is accumulating or removing charge at the b.c.p. The local
      form of the source function is applied to the study of the second-row diatomic
      hydride series and of a number of prototypical hydrogen-bonded systems.
      Differences in the local source contributions to the density at bond critical
      points due to chemical bonding (deformation density) and crystallization
      (interaction density) are also explored and found to be more informative and
      experimentally detectable than are the corresponding changes for the bond
      critical-point properties of weak intermolecular interactions. This result might
      be of potential interest when judging the data quality of a charge-density
      experimental determination. Although the present paper deals with electron
      densities derived from theoretical computations only, both the source function
      and its local form should also be easily obtainable from a charge-density quality
      X-ray diffraction experiment.

PMID- 15477684
TI  - The metal-insulator phase transition in mixed potassium-rubidium electro
      sodalites.
AB  - The collapse under pressure of the antiferromagnetic ground state of the
      potassium-rubidium electro-sodalite is studied using the linearized augmented
      plane wave with local orbitals method. Special considerations needed for setting
      up this basis for systems such as the electro-sodalites are discussed. It is
      demonstrated that the magnetism collapses at a unit-cell volume similar to
      potassium electro-sodalite and rubidium electro-sodalite. A critical pressure of
      8 GPa is predicted. The mechanism behind the collapse is a mixing of the F-center
      states with the highly diffuse unoccupied p states of the alkali atoms.

PMID- 15477685
TI  - Electron-density studies of molecular magnetic materials.
AB  - For more than forty years, the experimental determination and analysis of
      electron densities have played a fundamental role in advances in the chemical
      bond concept. The present paper illustrates the application of this approach to
      the field of molecular magnetism with examples that recently appeared in the
      literature. Particular attention is attached to several classes of materials,
      purely organic free radicals, coordination compounds and organometallic
      complexes, which exhibit specific magnetic behaviors. It is shown to what extent
      the electron-density analysis can shed light on bonding aspects that are closely
      related to magnetic couplings. Relations between spin delocalization, spin
      polarization, superexchange and the characteristics of the electron density are
      described. The use of the topological theory of 'atoms in molecules' allows the
      possible magnetic interaction pathways to be located and defined, especially
      through weak intermolecular contacts. The complementarity with polarized neutron
      diffraction and spin-density modeling techniques is particularly evident from the
      chosen examples.

PMID- 15477686
TI  - Studies of electric field induced structural and electron-density modifications
      by X-ray diffraction.
AB  - During the last two decades, a number of X-ray diffraction studies on the
      response of a crystal to an applied electric field have been carried out. In a
      few cases, the electron-density polarizations could be determined. The analysis
      of the induced variations of the structural properties on an atomic scale are of
      prime importance in order to acquire a better understanding of physical
      properties like the piezoelectric and dielectric properties of crystals. This
      article reviews the experimental technique used and the modelling methods of the
      Bragg scattering variations induced by the field. Some noteworthy results are
      presented that illustrate the possibility of detecting subtle structural changes,
      for example as small as 0.1 degrees in bond angles arising from applying a strong
      field, 10-40 kV cm(-1), as well as the pitfalls of such an approach for
      clarifying the relevance of the structural properties in physical mechanisms.

PMID- 15477687
TI  - 'In-situ' charge-density studies of photoinduced phenomena: possibilities for the
      future?
AB  - Over the past decade, there has been much development in the structure
      determination of photoinduced species by single-crystal X-ray diffraction. Such
      work is key to understanding many photoactivated chemical processes and physical
      properties that are behind phenomena such as photoisomerism, photoinduced
      chemical reactions, light-induced spin-crossover transitions and molecular
      excited states that are responsible for many types of fluorescence and
      phosphorescence. A brief overview of these experimental developments is presented
      in relation to the attraction of conducting charge-density studies on
      photoinduced structures. The technical issues regarding possible charge-density
      studies using these developments, both in the metastable and time-resolved
      domain, are highlighted in the form of a perspective towards future possibilities
      for photoinduced charge-density studies. The paper concludes with a summary of
      further experimental developments that are unfolding and how these may contribute
      to the ultimate viability of 'in-situ' charge-density studies on photoinduced
      phenomena.

PMID- 15477688
TI  - The experimental electron density in polymorphs A and B of the anti-ulcer drug
      famotidine.
AB  - Accurate structure factors have been measured for the two known conformational
      polymorphs (A and B) of famotidine up to a maximum resolution of
      sin(theta)/lambda = 1.2 A(-1) at 100 K using a conventional X-ray source and a
      CCD-based diffractometer. The experimental electron-density distribution was
      modelled using a multipole model and the interatomic interactions were analysed
      following the atoms-in-molecules theory. Excellent equivalence between most
      electronic and electrostatic properties in the polymorphs exists and no
      significant differences were found to exist across polymorphs either in the
      interatomic interactions (via the topological analysis) or in the atomic charges
      from integration of the atomic basins. Additional derived properties, such as the
      molecular dipole moment, similarly did not distinguish between the polymorphs.
      Only the molecular electrostatic potential mapped on top of the molecular
      surface, i.e. the isodensity contoured at 0.00675 e A(-3), was able to uncover
      the differences between A and B. In both conformations, the sizes of the
      electronegative and electropositive areas match. However, the average
      electrostatic potential in the electronegative area of A is -40 kJ mol(-1), while
      the corresponding value in B is -55 kJ mol(-1). Together with the physical shape
      and dimensions of A and B, this leads to a conclusion that the polymorphs are
      mutually exclusive at the same receptor binding site.

PMID- 15477689
TI  - Topological analyses and bond characterization of 1,3,5,7-tetra-tert-butyl-s
      indacene: a weak Csp3-H...H-Csp2-type dihydrogen interaction.
AB  - Topological analyses of experimental and theoretical calculated electron
      densities of 1,3,5,7-tetra-tert-butyl-s-indacene provide bond characterizations
      of the chemical bond and of the pi-delocalization. A weak C(sp(3))-H...H-C(sp(2))
      type intramolecular dihydrogen interaction (DHI) is identified through this
      analysis.

PMID- 15477690
TI  - An experimental (120 K) and theoretical electron-density study of KMnO4 and
      KClO4.
AB  - The experimental electron density rho(r) of the two isomorphic salts KMnO(4) and
      KClO(4) was determined by a multipole analysis of accurate X-ray diffraction data
      at 120 K. The quantum theory of atoms in molecules was applied to rho(r) and to
      its Laplacian nabla(2)rho(r). The bonds were characterized using the topological
      parameters at the bond critical points of the density rho(r), nabla(2)rho(r),
      G(r) (kinetic energy density), V(r) (potential energy density) and H(r) (total
      energy density). According to the classification recently proposed by Espinosa,
      Alkorta, Elguero & Molins [J. Chem. Phys. (2002), 117, 5529-5542], the K-O and Cl
      O bonds have a pure ionic and covalent character, respectively, while the Mn-O
      bonds show an intermediate behaviour. The results of the topological analysis of
      the experimental and theoretical (fully periodic Hartree-Fock and density
      functional calculations) electron density are in good agreement, even on a
      quantitative level. The atomic charges, determined by performing an integration
      over the topological basins, are about +2 e for Mn and Cl atoms. The ionic
      radius, estimated with the distance of the bond critical point from the nucleus,
      is in agreement with a charge of +2 e for the Mn atom.

PMID- 15477691
TI  - Variable-temperature X-ray crystallographic studies: a complementary tool for
      charge-density investigation of soft (organometallic) bonds.
AB  - Comparative X-ray diffraction studies at different temperatures are used to
      complement the information usually extracted from 'single-point' charge-density
      studies. The response of soft bonds against (temperature driven) changes of the
      crystalline environment might be indicative of some intramolecular mode
      associated with an incipient bonding. This is in fact confirmed for the anion
      [FeCo(CO)(8)](-) in the [(Ph(3)P)(2)N](+) salt. In contrast, the
      [Cr(2)H(CO)(10)](-) anion, whose conformation is known to strongly depend on the
      counterion, is actually insensitive to T variations in the
      [K(C(18)H(36)N(2)O(6))](+) salt.

PMID- 15477692
TI  - Electronic structure of the nickel(II) complex of the Schiff base of (S)-N-(2
      benzoylphenyl)-1-benzylprolinamide and glycine.
AB  - The experimental charge density of the Ni(II) complex of the Schiff base of (S)-N
      (2-benzoylphenyl)-1-benzylprolinamide and glycine was derived from high
      resolution single-crystal X-ray diffraction data (lambda = 0.5604 A) at low
      temperature (100 K) with synchrotron radiation at the beamline F1 using a CCD
      area detector. The central Ni atom is pseudo-square-planar coordinated by three N
      atoms [1.9414 (3), 1.8559 (3) and 1.8533 (3) A] and by one O atom [1.8620 (4) A].
      The N(1) atom is 0.359 A above the plane defined by the atoms Ni(1), N(2) and
      N(3). The d-orbital population analysis reveals an oxidation state for the Ni
      atom of +2 with the configuration d(8) and a hole mainly in the d(x(2)-y(2))
      orbital, located in the plane of the four ligating atoms. The prochiral reaction
      centre was examined by topological analysis.

PMID- 15477693
TI  - Predicting therapeutic response and degree of pituitary tumour shrinkage during
      treatment of acromegaly with octreotide LAR.
AB  - BACKGROUND/AIMS: The efficacy of transsphenoidal surgery in the treatment of
      patients with acromegaly is largely dependent on tumour size. A reduction in
      pituitary tumour volume by medical therapy might therefore improve subsequent
      surgical cure rates. This study prospectively determined the effects of the depot
      somatostatin analogue octreotide LAR on pituitary tumour size, GH and IGF-I
      levels and clinical symptoms in a cohort of previously untreated patients with
      acromegaly. METHODS: Six patients newly diagnosed with acromegaly (mean age 53
      years; range 42-76 years) received intramuscular octreotide LAR every 28 days for
      6 months. The initial dose of LAR was 20 mg, but increased to 30 mg after the
      initial 3 injections if mean GH levels were >5 mU/l. Prior to commencing LAR
      therapy, each patient received 3 injections of subcutaneous octreotide (50, 100
      and 200 mug) in a randomized order on separate days, and the serum GH response
      was measured. Pituitary tumour volume was calculated from MRI or computed
      tomography scans at baseline, then 3 and 6 months after initiation of treatment,
      and assessed by a 'blinded' radiologist in random order. At baseline, 4 patients
      had a macroadenoma and 2 patients had a microadenoma. For the latter, the whole
      gland volume was measured. RESULTS: Serum GH levels decreased from 29.6 +/- 19.2
      mU/l (mean +/- SD) at baseline to 12.1 +/- 10.5 mU/l at 3 months and 10.4 +/- 9.3
      mU/l at 6 months. Three patients achieved a mean serum GH level of <5 mU/l. In
      these patients, the serum GH had declined to <5 mU/l in response to a single 100
      mug subcutaneous octreotide injection. Serum IGF-I levels decreased by a mean of
      45 +/- 7.4%. Tumour volume decreased in all patients: mean baseline volume 2,175
      mm(3) (range 660-6,998) decreasing to 1,567 mm(3) (range 360-4,522) at 3 months
      (p < 0.05) and 1,293 mm(3) (range 280-4,104) at 6 months (p < 0.002). The mean
      percentage decrease in size was 29% (range -54 to +4%) at 3 months (p < 0.02) and
      47% (range 21-97%) at 6 months (p < 0.002). There was no statistically
      significant correlation between GH response and tumour shrinkage. CONCLUSIONS: A
      single test dose of subcutaneous octreotide may be useful in predicting the
      subsequent efficacy of octreotide LAR. Octreotide LAR results in significant
      shrinkage of pituitary tumours of newly diagnosed patients with acromegaly.
      Whether its administration to such patients for 6-12 months can improve the
      efficacy of subsequent transsphenoidal surgery will require further study.

PMID- 15477694
TI  - Improved arteriogenesis with simultaneous skeletal muscle repair in ischemic
      tissue by SCL(+) multipotent adult progenitor cell clones from peripheral blood.
AB  - BACKGROUND: The CD34(-) murine stem cell line RM26 cloned from peripheral blood
      mononuclear cells has been shown to generate hematopoietic progeny in lethally
      irradiated animals. The peripheral blood-derived cell clones expresses a variety
      of mesodermal and erythroid/myeloid transcription factors suggesting a
      multipotent differentiation potential like the bone marrow-derived 'multipotent
      adult progenitor cells' (MAP-C). METHODS: SCL(+) CD34(-) RM26 cells were
      transfused intravenously into mice suffering from chronic hind-limb ischemia,
      evaluating the effect of stem cells on collateral artery growth and simultaneous
      skeletal muscle repair. RESULTS: RM26 cells are capable of differentiating in
      vitro into endothelial cells when cultured on the appropriate collagen matrix.
      Activation of the SCL stem cell enhancer (SCL(+)) is mediated through the binding
      to two Ets and one GATA site and cells start to express milieu- and growth
      condition-dependent levels of the endothelial markers CD31 (PECAM) and Flt-1
      (VEGF-R1). Intravenously infused RM26 cells significantly improved the collateral
      blood flow (arteriogenesis) and neo-angiogenesis formation in a murine hind-limb
      ischemia transplant model. Although transplanted RM26 cells did not integrate
      into the growing collateral arteries, cells were found adjacent to local
      arteriogenesis, but instead integrated into the ischemic skeletal muscle
      exclusively in the affected limb for simultaneous tissue repair. CONCLUSION:
      These data suggest that molecularly primed hem-/mesangioblast-type adult
      progenitor cells can circulate in the peripheral blood improving perfusion of
      tissues with chronic ischemia and extending beyond the vascular compartment.

PMID- 15477695
TI  - Screening, diagnosis and advances in aortic aneurysm surgery.
AB  - BACKGROUND: Aortic aneurysms are common in the elderly and a frequent cause of
      sudden death. As elective aneurysm repair has a mortality drastically lower than
      that associated with rupture, the emphasis must be on early detection and repair
      free from complications. Recent advances include ultrasound screening for
      asymptomatic abdominal aortic aneurysm (AAA) and clinical trials on the size of
      AAA that require repair. Pre-operative assessment, management of cardiac risk,
      autologous blood transfusion strategies, and endovascular stent graft technology
      to avoid major open surgery are all issues to be addressed. METHODS: Following a
      computerized Medline search for publications on the detection and treatment of
      abdominal and thoracic aortic aneurysm, the publications identified were then
      read and the references within those publications examined for further
      publications on this topic. We have reviewed these publications without
      attempting a meta-analysis. RESULTS: Randomized population studies have addressed
      ultrasound screening for AAA. Attendance for screening was good and AAA detection
      inexpensive. Screening men from 65 years reduces the mortality from rupture and
      is cost-effective. Open thoracic and abdominal aneurysm repair has a mortality of
      around 8%, with myocardial infarction being a frequent cause of death. Pre
      operative reduction of cardiac risk by cardiac investigations and beta-blockade
      may reduce this mortality. Autologous transfusion techniques such as acute
      normovolaemic haemodilution and interoperative cell salvage reduce the need for
      allogeneic blood and the complications associated with open surgery. Minimally
      invasive endovascular repair is now possible for 40% of the AAA and an increasing
      proportion of thoracic aneurysms. CONCLUSIONS: The combination of screening,
      reduced pre-operative risk, and new minimally invasive techniques extends aortic
      aneurysm treatment into an increasingly elderly population. The combination of
      these techniques will reduce mortality from ruptured aortic aneurysm in the
      elderly and also reduce the stress associated with aneurysm surgery.

PMID- 15477696
TI  - Aging changes of the angioarchitecture and arterial morphology of the spinal cord
      in rats.
AB  - BACKGROUND: It is well known that vascular myelopathy increases with age,
      however, there are no systematic reports on the quantitative capillary density in
      the spinal cord and no reports concerning the age-related changes of vascularity
      and capillary density of the spinal cord. OBJECTIVE: Age-related changes of
      vascularity and capillary density of the spinal cord and the morphology of the
      ventral spinal artery were observed and measured so as to provide reference to
      study the microcirculation of the spinal cord. METHODS: Three different age
      groups of Wistar rats (1-2, 6-7 and >22 months old) were studied by ink-gelatin
      injection, corrosion casts, biological stereological technique, image analysis
      and transmission electron microscope. RESULTS: The number of central arteries per
      centimeter of the spinal cord decreased significantly with age; the ventral
      spinal artery and central arteries often became tortuous in the >22 month group.
      Capillary density in the anterior horn was significantly higher than that in the
      posterior horn. Capillary density in the gray matter decreased significantly with
      age. These aging changes of the ventral spinal artery in the rat included that
      the folds of internal elastic membrane were reduced, the internal elastic
      membrane thinned and disrupted, the endothelial cells degenerated and broke away
      from the wall, and smooth muscle cells in the tunica media degenerated and
      protruded to the lumen. The relative content of the elastic fibers decreased
      significantly with age, while the relative content of the collagenic fibers and
      the ratio of the C/E increased significantly with age. CONCLUSIONS: The
      difference between capillary density in gray and white matter in the spinal cord
      has shown that the need of metabolization is adapted to the function of the
      neurons, and the anterior horn is more sensitive than the posterior horn to
      anoxia and is easily damaged during ischemia in the spinal cord. Aging changes of
      capillary density and arterial morphology of the spinal cord may be important
      contributory factors in vascular myelopathy.

PMID- 15477697
TI  - Body composition by three-compartment model and relative validity of some methods
      to assess percentage body fat in mexican healthy elderly subjects.
AB  - BACKGROUND: In Mexico, there is scarce information about the body composition in
      the elderly. Some researchers have measured body fat by anthropometry and
      bioelectrical impedance. These techniques are practical and can be used in the
      field; however, proper validation is required. This implies the use of accurate
      and precise methods. In the elderly, Siri's three-compartment (3C) model has been
      proposed as feasible alternative to the gold standard four-compartment model.
      OBJECTIVE: To evaluate the body composition by the 3C model and the relative
      validity of densitometry and hydrometry methods to assess the percentage body fat
      (%BF) in 37 healthy Mexican elderly subjects. METHODS: The body density was
      measured by air displacement plethysmography, total body water was evaluated by
      means of an isotopic dilution technique, and two different hydration factors were
      used to determine the fat-free mass. These measurements were used to calculate
      %BF by the 3C model. Accuracy and precision of the methods were tested by a two
      way analysis of variance and regression procedures and bias by Bland and Altman
      analysis. RESULTS: In men and women as a whole group, the %BF by the 3C model was
      34.4 +/- 8.01. Women had higher values of %BF as compared with men (41.7 +/- 3.7
      vs. 29.4 +/- 6.4; p < 0.0001). The regression procedures showed that air
      displacement plethysmography was accurate and precise only in women and in the
      whole group. Regression analyses of %BF by total body water (using both hydration
      factors) and 3C model showed that the intercepts were not different from zero and
      that the slopes were not different from 1.0 in men and women separately and as
      group. CONCLUSION: In this study, the total-body water method revealed a good
      relative validity (accuracy, precision, and freedom from bias) as compared with
      the 3C model in men and women both separately and as a group and may be
      acceptable for the estimation of %BF in individuals or groups of healthy elderly
      subjects.

PMID- 15477699
TI  - Salivary cortisol level, salivary flow rate, and masticatory muscle activity in
      response to acute mental stress: a comparison between aged and young women.
AB  - BACKGROUND: Age-related effects on physiological stress reactions regarding
      changes in salivary cortisol concentration, saliva flow rate, and masticatory
      muscle activity, as well as the corresponding perceived mental stress and
      performance in response to acute stressors, have not yet been fully described.
      OBJECTIVE: Thus, the aim of this study was to assess the age-related variations
      in these variables in response to minor acute and naturalistic stressors in terms
      of computer tasks. METHODS: 13 aged (60-70 years old) and 13 young (20-30 years
      old) women with frequent practice and long experience with computer use were
      recruited by personal contact and flyers. The subjects were healthy and had full
      dental arches and no orofacial pain. The computer tasks were randomized and
      comprised a mentally demanding, modified Stroop colour-word test (CWT) and a less
      demanding reference test, both with a duration of 20 min and with equal physical
      demand. Visual analogue scales for global assessment of mental stress and
      perceived task difficulty and performance, measurements of saliva flow rate and
      cortisol concentration (unstimulated whole saliva), as well as surface
      electromyography of the temporalis and masseter muscles were used for assessment,
      and Spearman correlation analysis and Anova with repeated measures were used for
      statistical evaluation. RESULTS: The perceived task-related stress and task
      difficulty were significantly higher and the personal satisfaction with the task
      performance significantly poorer in the aged women. The cortisol concentration,
      indicating the stress level, showed a small, but significant increase in response
      to the tasks. Also the saliva flow rate increased. This response was most
      pronounced in the aged and during the CWT. The average electromyogram varied
      significantly between age groups and tasks, with higher levels and shorter
      relative periods with gaps in the aged women and in the CWT. In addition, the
      peak activity of the jaw elevator muscles at mouse clicking was significantly
      elevated as a form of co-activation or attention-related activity. CONCLUSIONS:
      The study showed marked differences in the response to mental demands in aged as
      compared with young women. The mental stress, reflected by increases of salivary
      cortisol concentration, saliva flow rate, visual analogue scale ratings, and
      activity level of the jaw elevator muscles, was more pronounced in the aged women
      in response to the computer tasks.

PMID- 15477700
TI  - Patient age and patency rate after recanalization of occluded peripheral
      arteries.
AB  - OBJECTIVES: Due to an increase in the percentage of older people in
      industrialized countries there is an increasing demand for medical care for the
      elderly. With advancing age, a series of structural, architectural and
      compositional modifications take place in the vasculature. Therefore, we analyzed
      the influence of patient age on the reocclusion rate of recanalized peripheral
      arteries. PATIENTS AND METHODS: 471 patients (mean age +/- SD: 62 +/- 12 years,
      range: 28-90 years) successfully treated by interventional recanalization were
      followed up (mean +/- SD: 18 +/- 17 months, range:6-48 months). Reocclusion of
      the recanalized arterial segment could be proven in 175 patients (37%), whereas
      octogenarians had the highest patency rate i.e. 68%. Univariate analysis,
      multivariate logistic regression analysis, and ROC analysis were performed.
      RESULTS: The univariate analysis showed a significant relation between
      reocclusion and PAOD stage, hyperlipoproteinemia, and total cholesterol level and
      erythrocyte sedimentation rate (ESR), respectively. Excluding age-related risk
      factors, the multivariate logistic regression analysis with backward selection
      reached a significant level for PAOD stage with p = 0.0012 and an odds ratio of
      1.63, and for ESR with a p = 0.0013 and an odds ratio of only 1.02. Age did not
      reach a significant level with a p value of 0.13 and an odds ratio of 0.98. In
      the ROC analysis, prognostic relevance could be shown for the combination of PAOD
      stage and ESR adjusted for age and hyperlipidemia, and for PAOD stage and ESR
      value as a single prognostic factor, but not for patient age. CONCLUSION: Thus,
      despite proven and hypothetical differences in the vascular biology of older
      people compared to younger people, age is not related to middle term patency
      rates after interventional recanalization of peripheral arterial occlusions.

PMID- 15477701
TI  - Field evaluation of cycled coupled movements of hand and foot in older
      individuals.
AB  - BACKGROUND: Age-related deterioration of motor performance has been investigated,
      often associated to behavioral slowing and to modification in the quality of
      movement coordination. However, the complexity of laboratory settings restrains
      sound quantitative evaluation of inter-limb coordination in large-scale clinical
      assessments, and no information regarding test stability has been provided.
      OBJECTIVE: The aims of the present study were to verify in homolateral hand and
      foot coordination field performances: (1) acceptable test-retest reliability
      criteria for older adults, and (2) the effects of coordination mode and test
      velocity at different ages across lifespan. METHODS: Seventy-seven individuals,
      ranging in age from 10 to 87 years, performed simultaneous flexions and
      extensions of the homolateral wrist and ankle in the sagittal plane with a 1:1
      ratio. Two homolateral conditions (preferred and non-preferred limbs) were tested
      in two coordination modes: in-phase (isodirectional) and anti-phase
      (nonisodirectional) at three test frequencies (80, 120 and 180 bpm,
      respectively). Time of correct execution within a maximum of 60 s was recorded
      for each test condition. Older adults (n = 36) performed the test and the retest
      with a week interval. RESULTS: High ICCs (range 0.72-0.98) and acceptable limits
      of agreement were found for the subsample of older adults. Main effects and
      significant interactions were found for age, coordination mode, and execution
      frequency. Time of correct execution was longest in younger adults and shortest
      in older individuals. At all ages, it was longer for the in-phase than in the
      anti-phase condition and decreased with increasing execution frequency. However,
      the amplitude of the differences between execution frequencies varied as a
      function of age and coordination mode. CONCLUSIONS: The high test-retest
      stability coefficients confirm that the present field test represents a reliable
      tool to quantify older individual's performance on cyclic coupled movements of
      hand and foot allowing large-scale evaluations with an inexpensive apparatus.
      Aging generally harms homolateral inter-limb coordination performance, but a more
      complex pattern of effects emerges when coordination mode, and frequency of
      execution are manipulated. In fact, age-related performance impairments were most
      pronounced during anti-phase movements, that need increased monitoring and
      attentional allocation in order to inhibit the natural in-phase mode, and at high
      execution frequencies, that are strongly affected by age-related muscle weakness,
      prolonged reaction times, and changes in stretch reflexes.

PMID- 15477698
TI  - Balance confidence improves with resistance or agility training. Increase is not
      correlated with objective changes in fall risk and physical abilities.
AB  - BACKGROUND: While the fear of falling is a common psychological consequence of
      falling, older adults who have not fallen also frequently report this fear. Fear
      of falling can lead to activity restriction that is self-imposed rather than due
      to actual physical impairments. Evidence suggests that exercise can significantly
      improve balance confidence, as measured by falls-related self-efficacy scales.
      However, there are no prospective reports that correlate change in balance
      confidence with changes in fall risk and physical abilities as induced by
      participating in a group-based exercise program. OBJECTIVE: The primary purpose
      of this prospective study was to examine the relationship between the change in
      balance confidence and the changes in fall risk and physical abilities in older
      women with confirmed low bone mass after 13 weeks of exercise participation. The
      secondary purpose of this study was to examine the relationship between the
      change in balance confidence and the change in physical activity level. METHODS:
      The sample comprised 98 women aged 75-85 years with low bone mass. Participants
      were randomly assigned to one of three groups: resistance training (n = 32),
      agility training (n = 34), and stretching (sham) exercises (n = 32). The 50-min
      exercise classes for each study arm were held twice weekly at a local YMCA
      community centre. RESULTS: Both resistance training and agility training
      significantly improved balance confidence by 6% from baseline after 13 weeks.
      However, the change in balance confidence was only weakly correlated with
      improved general physical function and not significantly correlated with the
      changes in fall risk score, postural stability, gait speed, or physical activity
      level. As well, we observed balance confidence enhancement in the presence of
      increased fall risk or deterioration in physical abilities. CONCLUSIONS: Two
      different types of exercise training improved balance confidence in older women
      with low bone mass. This change in balance confidence was significantly
      correlated with change in general physical function. Because of the observation
      of discordance between balance confidence change and changes in fall risk and
      physical abilities, those who design group-based exercise programs for community
      dwelling older adults may wish to consider including an education component on
      factors that influence fear of falling. Objective changes in fall risk factors
      cannot be assumed to mirror change in fear of falling and physical abilities in
      older adults in the short-term.

PMID- 15477702
TI  - Quality of life in the very elderly after cardiac surgery: a comparison of SF-36
      between long-term survivors and an age-matched population.
AB  - BACKGROUND: Octogenarians are the fastest growing section of the population in
      Western countries. Since health care resources are limited, there is a need for
      critical evaluations of the long-term surgical outcome and quality of life in the
      elderly. OBJECTIVES: Our aim was to assess the quality of life and long-term
      survival after cardiac surgery in the very elderly. METHODS: Between 1990 and
      1993, 117 octogenarians underwent aortic valve replacement, coronary artery
      bypass grafting or combined surgery at our department. Forty-one patients were
      still alive at the time of follow-up (mean 8.3 +/- 1.9 years). Thirty-nine of the
      41 long-term survivors (95%) answered a quality of life questionnaire (SF-36).
      The scores were compared with an age-matched population. RESULTS: The overall
      survival at 1, 5 and 9 years was 92.3 +/- 2.5, 65.0 +/- 4.4 and 37.9 +/- 5.2%,
      respectively. A significant difference was identified between the scores of our
      patients and the general Swedish octogenarians in two SF-36 headings (Bodily Pain
      and Physical Functioning). Our patients indicated lower physical function, but
      less pain in comparison with the general aged population. There was no
      significant difference in six of the eight SF-36 headings. CONCLUSIONS: The
      overall long-term survival was similar to Swedish octogenarians. Late
      postoperative quality of life in our long-term survivors was comparable to an age
      matched population. Our findings support the view that a selected population of
      elderly may undergo open heart surgery with good long-term quality of life.

PMID- 15477703
TI  - Fall incidence in frail older women after individualized visual feedback-based
      balance training.
AB  - BACKGROUND: The knowledge concerning balance training actually lowering fall
      rates among frail older persons is limited. OBJECTIVE: The aim of this study was
      to examine the effects of a 4-week individualized visual feedback-based balance
      training on the fall incidence during 1-year follow-up among frail older women
      living in residential care. METHODS: Twenty-seven older women from 2 residential
      care homes were randomized into exercise (n = 20) and control (n = 7) groups.
      Balance measurements were carried out before and after a 4-week training period
      and falls were monitored by monthly diaries for 1 year. An interview about fear
      of falling and physical activity was completed before and after the intervention
      and after the 1-year follow-up. RESULTS: A positive effect of balance training on
      fall incidence was found. A dynamic Poisson regression model showed that during
      the follow-up the monthly risk of falling was decreased in the exercise group
      compared to controls (risk ratio 0.398, 95% CI 0.174-0.911, p = 0.029). In
      addition, the exercise group reported a reduced fear of falling and increased
      physical activity after a training period but these changes declined during the
      follow-up period. CONCLUSION: Individualized visual feedback-based balance
      training was shown to be a promising method for fall prevention among frail older
      women. High compliance (97.5%) with the training program showed that carefully
      targeted training programs can be carried out among older people with health
      limitations.

PMID- 15477704
TI  - Prevention of late complications by half-solid enteral nutrients in percutaneous
      endoscopic gastrostomy tube feeding.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy feeding is accompanied by unique
      complications, which are not easily controlled. OBJECTIVE: In an attempt to
      decrease complications, we used half-solid nutrients for percutaneous endoscopic
      gastrostomy feeding in an 85-year-old woman. The patient had been receiving
      enteral nutrients via percutaneous endoscopic gastrostomy, and we examined
      whether this approach can reduce complications. She presented with regurgitation
      of enteral nutrients and recurrent respiratory infections. METHODS: Half-solid
      enteral nutrients, prepared by mixing liquid enteral nutrients with agar powder,
      were administered via percutaneous endoscopic gastrostomy. RESULTS: Symptoms of
      gastroesophageal reflux disappeared immediately after the start of half-solid
      enteral nutrient feeding. CONCLUSION: Gastroesophageal reflux and leakage, two
      intractable late complications of percutaneous endoscopic gastrostomy tube
      feeding, can be alleviated by the solidification of enteral nutrients. Since this
      method allows quick administration of nutrients, it is also expected to help
      prevent the occurrence of decubitus ulcers and reduce the burden to the
      caregiver.

PMID- 15477705
TI  - New trends in biomedical aging research.
AB  - BACKGROUND: The increasing demand for health care services, the extraordinary
      results obtained by applying innovative biotechnology, and the intense debate
      aroused by the possibility that postponement of aging may be in sight should
      promote public enthusiasm and funding for biomedical aging research aimed at
      enhancing a healthy life span by healthy productive life. OBJECTIVE: New trends
      in biomedical aging research arise from the advancement of knowledge on the basic
      molecular mechanisms of aging and the availability of advanced biotechnology.
      RESULTS: The emerging scenario is that, in opposition to the highly publicized,
      yet unwarranted claims of existing so-called anti-aging treatments, innovative
      and promising therapies for the treatment and prevention of age-related diseases
      and intriguing strategies aimed at the postponement of aging are currently in the
      process of development. CONCLUSIONS: Although many problems will remain unsolved
      for long, it seems that a common consensus has been raised towards the possible
      serious impact of these strategies on the development of knowledge around the
      mechanisms of aging.

PMID- 15477707
TI  - Epidemiology of neuroendocrine tumours.
AB  - Neuroendocrine tumours account for only 0.5% of all malignancies. The incidence
      is approximately 2/100,000 with a female preponderance under the age of 50 years
      due to appendiceal location. The main primary sites are the gastrointestinal
      tract (62-67%) and the lung (22-27%). Presentation with metastatic disease
      accounts for 12-22%. In the last decades, the incidence has been rising. This
      might be due to more awareness, improved diagnostic tools or a change in
      definition. Most neuroendocrine tumours are mainly sporadic, but association with
      the multiple endocrine neoplasia type 1 syndrome and clustering within families
      is known. Also an increased risk of secondary cancers has been reported, but
      numbers are small. The 5-year survival is mainly associated with stage: 93% in
      local disease, 74% in regional disease and 19% in metastatic disease. In
      metastatic disease, survival increased since 1992, when treatment with octreotide
      became largely available in The Netherlands.

PMID- 15477708
TI  - Tumour biology of gastroenteropancreatic neuroendocrine tumours.
AB  - Neuroendocrine tumours of the gastroenteropancreatic tract (GEP NETs) represent a
      rare and heterogeneous group of tumours. Based on their ontogenetic origin, GEP
      NETs are classified into foregut, midgut and hindgut tumours. Although they have
      many features in common, their molecular backgrounds are obviously different.
      Elucidation of the key factors determining tumour biology has been hampered by
      the low incidence and high variability of these tumours in terms of origin,
      morphology and growth. However, recent years have shed some light on molecular
      genetics of these tumours, revealing important genetic factors as the RET proto
      oncogene and the tumour suppressor menin as well as knowledge about the role of
      growth factors like IGF-1, TGF-beta, VEGF and PDGF for the regulation of
      differentiation, growth and secretion. In the future, emerging molecular tools in
      rapid individual genome analysis and in proteomic and array technologies may help
      to delineate common patterns of NET disease.

PMID- 15477709
TI  - Endocrine tumors of the gut and pancreas tumor biology and classification.
AB  - The endocrine tumors of the gut and pancreas tract are a group of neoplasms
      composed of cells with a neuroendocrine phenotype. Well-differentiated tumors,
      well-differentiated carcinomas and poorly differentiated carcinomas are the major
      categories identified. According to their localization (stomach, duodenum
      jejunum, ileum, appendix and colorectum), they display distinct phenotypes,
      regarding their pathology, immunohistochemistry and hormonal syndromes. Their
      clinical behavior spans from benign, uncertain malignant potential, low-grade
      malignant to high-grade malignant. Currently, extensive work is performed to
      unravel the genetic background.

PMID- 15477710
TI  - Gastric neuroendocrine tumors.
AB  - Gastric carcinoids are rare neuroendocrine tumors, usually classified as type I,
      if associated with atrophic body gastritis; type II, if associated with Zollinger
      Ellison syndrome and multiple endocrine neoplasia type I, and type III, in the
      absence of any gastric pathology (sporadic tumors). The pathological features, as
      well as the prognosis of the tumor and the patient's survival strictly depend on
      this classification. The correct management of the patient with gastric carcinoid
      can only be proposed when the tumor has been classified by an accurate
      pathological and clinical evaluation of the patient. While the therapeutic
      approach in types I and II is based on a conservative strategy, including
      endoscopic resection, an adequate follow-up program, and the possible use of
      somatostatin analogues, an aggressive surgical approach is required in type III.

PMID- 15477711
TI  - Insulinoma.
AB  - More than 90% of insulinomas are benign tumors. Insulinomas cause hypoglycemia
      and thereby symptoms of neuroglycopenia and catecholamine response. During
      symptoms, blood glucose levels should be less than 40 mg/dl (less than 2.2
      mmol/l), concomitant insulin levels should be > or =6 IU/ml (> or =43 pmol/l) and
      concomitant C-peptide levels > or =0.2 pmol/l. Most insulinomas can be identified
      intraoperatively by experienced surgeons. Initial therapy consists of
      administration of frequent meals and/or by glucose infusion. In patients with
      solitary insulinomas, complete surgical removal of the tumor should be the
      primary goal. In patients with metastatic insulinomas, symptoms of insulin
      hypersecretion will only completely disappear after complete resection of all
      metastases.

PMID- 15477712
TI  - Gastrinomas: advances in diagnosis and management.
AB  - Gastrinomas causing Zollinger-Ellison syndrome (ZES) are the most common
      functional, malignant pancreatic endocrine tumors. In this paper, the diagnosis
      and treatment of these tumors are reviewed, incorporating recent advances in each
      area. Furthermore, recent advances in their pathology, molecular pathogenesis,
      and aspects of their localization using somatostatin receptor scintigraphy, as
      well as their treatment are discussed. Recent data from our NIH prospective
      studies on patients with ZES are included to illustrate many of these points.

PMID- 15477713
TI  - Complications of midgut carcinoid tumors and carcinoid syndrome.
AB  - The carcinoid syndrome, associated with carcinoid tumors of the midgut, consists
      of symptoms such as diarrhea, flushing, wheezing and cardiovascular symptoms.
      This review focuses on these symptoms and discusses therapeutic options. The
      symptoms are caused by the secretion of biogenic amines, polypeptides and other
      factors of which serotonin is the most prominent. However, diarrhea is also due
      to factors such as malabsorption. Besides antitumor therapy, more specific
      interventions such as serotonin receptor blockers can be useful. The carcinoid
      heart disease involves the tricuspid and pulmonary valve. In the pathogenesis,
      serotonin plays a central role. The therapeutic approach is mostly symptomatic.
      Other cardiovascular complications include bowel ischemia and hypertension.
      Pellagra and psychiatric symptoms are due to a depletion of tryptophan, which is
      consumed by the carcinoid tumor for serotonin synthesis. Finally, follow-up and
      clinical practice of patients with carcinoid tumors are discussed.

PMID- 15477714
TI  - Carcinoids of the appendix.

PMID- 15477715
TI  - Diagnosis of non-functioning neuro-endocrine gastro-enteropancreatic tumours.
AB  - Non-functioning neuro-endocrine gastro-enteropancreatic tumours are neoplasms of
      neuro-endocrine differentiation without symptoms of hormonal hypersecretion. In
      pancreatic tumours, symptoms are related to an expanding tumour mass, while most
      midgut tumours are small and symptoms of intermittent intestinal entrapment are
      due to mesenteric fibrosis. Positive somatostatin receptor imaging indicates the
      neuro-endocrine differentiation of the tumour. The high spatial resolution of
      MRI/CT improves preoperative planning. In localized pancreatic tumours, curative
      resection of the primary improves survival. In midgut tumours, resection of the
      primary should be performed, irrespective of the presence of liver metastases.
      Palliative surgery and cytoreductive therapy of liver metastases may prolong
      survival in both, pancreatic and midgut tumours. Combination chemotherapy is
      effective in pancreatic disease, while in midgut tumours the response rate is
      only 22%. As the antiproliferative effect of biotherapy is still uncertain, it
      cannot yet be recommended as a routine treatment in non-functioning neuro
      endocrine gastro-enteropancreatic tumours.

PMID- 15477716
TI  - When to look for Von Hippel-Lindau disease in gastroenteropancreatic
      neuroendocrine tumors?
AB  - Von Hippel-Lindau (VHL) disease is a progressive autosomal dominant multisystem
      disorder that is associated with a germ line mutation of the VHL gene on the
      short arm of chromosome 3. A variety of benign and malignant diseases, including
      eye and CNS hemangioblastomas, renal cell carcinoma and pheochromocytoma are the
      major components. Gastroenteropancreatic neuroendocrine tumors are also listed
      among the typical complications, although these occur seldom. Virtually all such
      tumors are pancreatic islet cell tumors. VHL-associated islet cell tumors are
      mostly hormone-inactive. They can be detected during screening investigations
      according to the multidisciplinary disorder or by workup of space-occupying
      lesions. There are no specific predictors for malignancy in VHL-associated islet
      cell neoplasias, but tumors smaller than 3 cm in diameter are believed to be
      always benign. Gadolinium-enhanced MRI is currently the imaging method of choice,
      but contrast-enhanced CT is also a diagnostic option. The spectrum of
      manifestations is illustrated by selected cases.

PMID- 15477717
TI  - Functional activity of the multiligand analog SOM230 at human recombinant
      somatostatin receptor subtypes supports its usefulness in neuroendocrine tumors.
AB  - Functional gastroenteropancreatic tumors express all 5 somatostatin receptor
      subtypes (sst) in different quantities. Octreotide and lanreotide treat patients
      with these tumors by binding preferentially to sst2 and, to a lesser extent, to
      sst3 and sst5 receptors, thereby controlling prominent symptoms caused by hormone
      hypersecretion (diarrhea and flushing). Although symptoms initially improve in
      most patients, a loss of response occurs in about 50% during continuous
      treatment. The functional activity at sst receptors of SOM230, a new multiligand
      somatostatin analog, has been described and compared with that of somatostatin
      (SRIF-14) and octreotide. These data show that SOM230 is a full agonist with
      nanomolar potency at sst(1,2,3) and sst5 receptors. The multiligand activity
      profile of SOM230, together with its nondesensitizing inhibitory effect on growth
      hormone and insulin-like growth factor-I secretion in rats, may underlie its
      successful use in clinical trials and its potential for use in refractory
      patients with carcinoid tumors.

PMID- 15477718
TI  - Somatostatin and other Peptide receptors as tools for tumor diagnosis and
      treatment.
AB  - Somatostatin receptors are expressed in selected human cancers. They are
      particularly frequently expressed in gastroenteropancreatic neuroendocrine tumors
      (GEP NET), including both primaries and metastases. The density is often high,
      the distribution is usually homogeneous. While various somatostatin receptor
      subtypes can be expressed in these tumors, sst2 is clearly predominant. These
      receptors represent the molecular basis for a number of clinical applications,
      including symptomatic therapy with cold octreotide in hormone-secreting GEP NET,
      in vivo diagnostic with Octreoscan to evaluate the extend of the disease, and 90Y
      DOTATOC radiotherapy. GEP NET can, however, express peptide receptors other than
      somatostatin receptors: insulinomas have more glucagon-like peptide 1 receptors
      than somatostatin receptors, gut NET (carcinoids) may also express
      cholecystokinin 2, bombesin or vasoactive intestinal peptide receptors. Often,
      several of these peptide receptors are expressed simultaneously in GEP NET,
      providing a molecular basis for in vivo multireceptor targeting of those tumors.

PMID- 15477719
TI  - Future aspects of somatostatin-receptor-mediated therapy.
AB  - More than 30 years have passed since somatostatin was discovered and its hormonal
      function defined. The wide range of anatomical distribution and actions of
      somatostatin and its receptors have stimulated intense scientific and clinical
      interest. The development of somatostatin analogues helped define its usefulness
      in the treatment of endocrine diseases and cancer. The molecular cloning of five
      distinct subtypes of somatostatin receptors in the 1980s has significantly
      increased our insight into the biology of somatostatin and its receptor subtypes
      and has led to the design and development of subtype-selective peptides and
      nonpeptide agonists and antagonists. In the future, the development of
      somatostatin-receptor-mediated treatment will go along different lines. Tumor
      targeted radioactive treatment based on somatostatin analogues will be further
      developed and improved. New somatostatin analogues will come into clinical
      practice, both receptor subtype-specific analogues, but also pan-receptor
      analogues. One is currently in clinical trial--SOM230--which is a cyclo
      hexapeptide binding with high affinity to receptor type 1, 2, 3 and 5, but not 4.
      It has already shown activity both in acromegaly and in neuroendocrine
      gastrointestinal tumors. Preclinical studies on somatostatin analogues, coupled
      to cytotoxic agents, have shown rather promising results and will hopefully be
      further developed in clinical trials. Another interesting area is treatment of
      neuroendocrine gut tumors with ultra-high doses of somatostatin analogues, which
      has demonstrated significant clinical effects in patients resistant to standard
      dose treatment with the same somatostatin analogue.

PMID- 15477720
TI  - Surgical treatment of endocrine pancreatic tumours.
AB  - Endocrine pancreatic tumours (EPTs) are uncommon, with a major challenge to alert
      physicians to their recognition and requirements of treatment. Functioning EPTs
      cause well-known clinical syndromes of hormone excess. Insulinomas, gastrinomas
      and glucagonomas are most common; vipomas and somatostatinomas are rare. EPTs
      also occur as non-functioning lesions without symptoms of hormone excess
      occasionally with ectopic hormone, such as ACTH and Cushing syndrome as a late
      complication. The majority of EPTs are sporadic, but they may also be part of a
      multiple endocrine neoplasia type 1 syndrome or rarely the von Hippel-Lindau
      syndrome. EPTs have been of great interest to endocrine surgeons and we have,
      during recent years, witnessed continuing advances in diagnosis, imaging and
      treatment of the different tumour entities. It has become obvious that surgical
      treatment of these tumours is of increased concern and can have a marked impact
      on symptoms and survival.

PMID- 15477721
TI  - Interventional treatment of the carcinoid syndrome.
AB  - Liver metastases imply a major problem in patients with carcinoid tumours and
      hormone overproduction. Patients with distant metastases can undergo resection
      for potential cure or for symptom palliation. In patients with bilobar liver
      metastases other interventions are at hand, e.g. local ablation or hepatic
      arterial embolization. In selected cases liver transplantation can be a treatment
      alternative. Prior to all interventions patients with midgut carcinoids are
      protected with somatostatin analogues to reduce hormone secretion. Patients with
      foregut carcinoids may present special problems with life-threatening release of
      histamine during interventions.

PMID- 15477722
TI  - Ablative therapies for liver metastases of gastroenteropancreatic endocrine
      tumors.
AB  - Hepatic metastases are frequent in patients with gastroenteropancreatic (GEP)
      endocrine tumors. The presence of hepatic metastases affects overall prognosis
      and quality of life especially in the presence of debilitating functional
      syndromes. Surgery, although the method of choice for hepatic metastases, is
      usually impossible due to disease extent. Results of systemic chemotherapy are
      also disappointing especially in patients with metastases from midgut GEP tumors.
      These latter patients usually have carcinoid syndrome which can be controlled by
      somatostatin analogues. Other therapeutic options in the treatment of highly
      vascular liver metastases from GEP tumors are locoregional strategies by inducing
      vascular occlusion resulting in ischemia and necrosis of tumoral tissue. Surgical
      ligation of the hepatic artery or transient hepatic ischemia has been replaced by
      transcatheter arterial chemoembolization (TACE). TACE has proven effective in
      controlling symptoms and gives objective tumor response in about half of
      patients. Other regional destructive methods, used either alone or in combination
      with surgery, include radiofrequency ablation and cryotherapy. The latter
      strategies are poorly evaluated to date and are usually adjuncts to surgery and
      reserved for limited disease.

PMID- 15477723
TI  - Chemotherapy for gastro-enteropancreatic endocrine tumours.
AB  - Despite similar histological and morphological aspects, gastro-enteropancreatic
      (GEP) endocrine tumours represent a heterogeneous group of tumours with varying
      clinical expression depending on tumour type (functional or not), origin and
      extension, but also on histological differentiation and proliferative capacity.
      The natural history of well-differentiated tumours is often favourable without
      treatment and GEP endocrine tumours may remain indolent for many years.
      Chemotherapy may however be indicated in the presence of symptomatic non
      progressive disease (progression evaluated over 3-6 months). In contrast, poorly
      differentiated GEP endocrine tumours are frequently aggressive and early
      treatment is required. Accurate staging is mandatory and where surgery is
      possible (even in the event of limited metastatic disease), this option should be
      re-evaluated in a multidisciplinary approach. Approximately 2/3 of malignant GEP
      tumours are metastatic at discovery and surgery is possible in a minority of
      patients; therefore, chemotherapy, with/without other strategies (e.g. local
      ablation), is frequently indicated in patients with symptomatic, bulky or
      progressive disease. For well-differentiated pancreatic tumours, the reference
      association is Adriamycin with streptozotocin yielding objective responses (OR)
      in 40-60% of patients. Prolonged treatment is limited due to potential
      cardiotoxicity of Adriamycin and standard 2nd-line regimens are not of proven
      efficacy; thus, other treatment modalities are usually additionally required
      (e.g. chemo-embolisation). A significant OR may render a small number of patients
      secondarily amenable to surgery. Published series evaluating chemotherapy for
      midgut endocrine tumours are outdated and disappointing. Objective response rates
      with combined associations (including either 5-fluorouracil and/or
      streptozotocin) rarely exceed 20% and where possible, chemo-embolisation for
      hepatic metastases combined with somatostatin analogues (+/- interferon) should
      be preferred. Poorly differentiated GEP tumours are generally aggressive tumours
      with metastases at diagnosis and tend to progress rapidly. Surgery is rarely
      possible and ineffective even in locally advanced disease due to a high risk of
      recurrence. Chemotherapy, using cisplatin and etoposide, is the reference
      treatment and frequently yields OR rates >50%. However, despite being
      chemosensitive, disease control is limited (8-10 months). Overall, advances in
      therapeutic chemotherapeutic options are required in the management of all types
      of advanced GEP endocrine tumours and evaluation of new drugs (e.g. irinotecan)
      and combination strategies (chemotherapy with local ablative therapies) are
      required in the future.

PMID- 15477724
TI  - Interferon-alpha: regulatory effects on cell cycle and angiogenesis.
AB  - In the current study, we investigated the effects of interferon-alpha (IFN-alpha)
      on proliferation and angiogenesis in neuroendocrine tumor disease. Using a panel
      of human neuroendocrine tumor cell lines, we confirmed functionally active IFN
      alpha signaling by STAT activation and nuclear translocation as well as
      transactivation. IFN-alpha results in anchorage-dependent and -independent growth
      inhibition due to a delayed progression from S-phase to G2 phase of the cell
      cycle. This was due to substantial reduction in cellular cyclin B levels
      resulting in the inhibition of Cdc2 kinase activity. In parallel to growth
      inhibition, we observed a profound inhibition of VEGF gene transcription by IFN
      alpha in human neuroendocrine tumor cells due to an Sp1/Sp3-dependent inhibition
      of VEGF promoter activity. Treatment of neuroendocrine tumors with IFN-alpha in
      nude mice resulted in growth inhibition and inhibition of angiogenesis.
      Furthermore, treatment of neuroendocrine tumor patients with IFN-alpha resulted
      in decreased VEGF expression as well as tumor angiogenesis in liver metastases.
      In summary, IFN-alpha acts via direct antiproliferative effects as well as
      inhibition of tumor angiogenesis mediated by suppression of VEGF gene expression
      in neuroendocrine tumor disease.

PMID- 15477725
TI  - From basic to clinical research in gastroenteropancreatic neuroendocrine tumor
      disease -- the clinician-scientist perspective.
AB  - Patients with rare tumors represent a diagnostic and therapeutic challenge for
      non-specialized physicians, surgeons and other medical doctors. Whereas several
      specialized centers have gathered data for an improved diagnosis and therapy of
      neuroendocrine tumor disease, numerous clinical issues have not been resolved on
      an evidence-based medicine level. Furthermore, the evaluation of new treatment
      options has been overshadowed by the low incidence of the disease. In this
      article, a major medical challenge for the diagnosis and therapy of
      neuroendocrine tumor disease is addressed. As well, new therapeutic treatment
      options translated from current findings in the fields of molecular and tumor
      biology are discussed.

PMID- 15477726
TI  - The role of eggs, margarines and fish oils in the nutritional management of
      coronary artery disease and strokes.
AB  - Although egg yolk is a rich source of cholesterol, the effect of eggs in raising
      serum cholesterol is variable and in some subjects there is no effect whatsoever.
      However, oxidized cholesterol can increase atherosclerosis even with normal serum
      cholesterol. In order to attenuate oxidation of cholesterol in eggs, it is
      necessary to limit the degree of heat applied. This means that we should use only
      soft-boiled eggs which should be almost like water. We can also avoid egg yolk
      altogether and get a highly nutritious egg food from the egg white alone. The
      saturated fats from milk products, especially butter, are highly atherogenic.
      There are available many butter substitutes in the form of margarines. But many
      of these margarines have hydrogenated vegetable oils which result in the
      production of trans-fatty acids. The trans-fatty acids are as atherogenic as
      saturated fats. There are available, however, margarines without the trans-fatty
      acids. These are found only in large supermarkets. Fish oils contain N3 fatty
      acids which, unlike vegetable oils which contain N6 fatty-acids, can prevent
      atherosclerosis and sudden death by counteracting ventricular arrhythmias, acting
      as antioxidants, antithrombotic, anti-inflammatory agents, and decreasing
      triglycerides and blood pressure.

PMID- 15477727
TI  - Interactions between medicines and functional foods or dietary supplements.
AB  - Recently, the demand for supplements has steadily been increasing with the
      diffusion of alternative and supplemental medicines throughout the world.
      Therefore, the supplements have frequently been taken with many drugs. Here, we
      have introduced the pharmacokinetic and pharmacological interactions between
      them.

PMID- 15477728
TI  - Peripheral B lymphocyte tolerance.
AB  - This lecture discusses two interrelated topics, B cell tolerance in the
      peripheral immune system and BAFF. Using the 3-83 antibody transgenic mouse bred
      to mice carrying cognate antigen in the liver, we previously found that clonal
      elimination drastically reduced the precursor frequency of autoreactive cells.
      The consensus model to explain this tolerance is the 2-signal hypothesis, which
      proposes that in the absence of T cell help BCR stimulation is a negative signal
      for B cells. However, this model fails to explain how these same B cells can
      respond to T-independent type II (TI-2) antigens, raising the question of how
      they distinguish TI-2 antigens from multimeric self determinants. We propose that
      B cells use NK-like missing self recognition to provide the needed specificity,
      as foreign antigens are unlikely to carry self markers. The model has
      implications for the evolution of the immune system, B lymphocyte signaling,
      tissue specificity of autoimmunity, and microbial subversion of the immune
      system. Overexpression of the critical B cell survival cytokine BAFF/BLyS has
      been associated with autoimmunity. We have discovered a novel splice isoform that
      regulates BAFF activity and may play a role in limiting B cell activity. The
      novel form, called DBAFF, is able to heteromultimerize with normal BAFF and can
      suppress receptor binding and proteolytic release from the cell surface.
      Preliminary studies from transgenic mice overexpressing wild type or DBAFF are
      consistent with a possible regulatory role for DBAFF, raising the possibility
      that the relative expression levels of BAFF and DBAFF regulates tolerance.

PMID- 15477729
TI  - Porifera a reference phylum for evolution and bioprospecting: the power of marine
      genomics.
AB  - The term Urmetazoa, as the hypothetical metazoan ancestor, was introduced to
      highlight the finding that all metazoan phyla including the Porifera [sponges]
      derived from one common ancestor. Analyses of sponge genomes, from Demospongiae,
      Calcarea and Hexactinellida have permitted the reconstruction of the evolutionary
      trail from Fungi to Metazoa. This has provided evidence that the characteristic
      evolutionary novelties of Metazoa existing in Porifera share high sequence
      similarities and in some aspects also functional similarities to related
      polypeptides found in other metazoan phyla. It is surprising that the genome of
      Porifera is large and comprises substantially more genes than Protostomia and
      Deuterostomia. On the basis of solid taxonomy and ecological data, the high value
      of this phylum for human application becomes obvious especially with regard to
      the field of chemical ecology and the hope to find novel potential drugs for
      clinical use. In addition, the benefit of efforts in understanding molecular
      biodiversity with focus on sponges can be seen in the fact that these animals as
      "living fossils" allow to stethoscope into the past of our globe especially with
      respect to the evolution of Metazoa.

PMID- 15477730
TI  - Receptor technology--cell binding to P-15: a new method of regenerating bone
      quickly and safely-preliminary histomorphometrical and mechanical results in
      sinus floor augmentations.
AB  - Modern implantology involves the application and optimization of bone engineering
      biomaterials and scaffolds to achieve predictability in quality and quantity of
      the regeneration result and to avoid the high morbidity factor of the present
      gold standard. In this respect, acceleration of (woven) bone formation and
      completeness of the regeneration result seems to be an reasonable attempt by
      multiplication of the whole cascades by duplicating all phases of cell binding,
      migration, proliferation and differentiation. Collagen I is an extracellular
      matrix protein with multiple main binding domains for osteogenic progenitor cells
      and therefore plays a crucial role in osteogenesis. PepGen P15 is the first man
      engineered collagen I binding domain for potential osteoblasts and is able to
      multiply the complete regeneration cascade. The article explains the principles
      of micromolecular receptor engineering and its application in sinus floor
      augmentations as a preliminary report. It presents the first clinical and
      histomorphometrical results of this new technology in sinus floor elevations. The
      future potential of individual bone regeneration will be discussed.

PMID- 15477731
TI  - Japan's share of research output in basic medical science.
AB  - OBJECTIVE: To investigate the degree of Japan's contribution to the research in
      basic biomedical science in the last decade. METHODS: Articles published during
      1991-2000 in highly reputed basic biomedical science journals (10 journals from
      each of the 16 categories related to basic biomedical science) were accessed
      through Medline database. The number of articles having affiliation with a
      Japanese institution was then determined using appropriate search strategies.
      RESULTS: In total 312,748 articles were published in the selected journals and
      Japan's share was 20,665 articles (6.6% of total) with an upward trend over time
      (p=0.01). Japan's share was higher in the journals, which publish mostly original
      articles (6.9%) than that in the journals, which publish only review articles
      (2.6%). The former group showed an upward trend (p=0.01) over time (1991-2000)
      while the latter did not (p=0.08). Among the 16 categories, Japan had
      significantly positive trend in 7 categories while others remained unchanged.
      CONCLUSIONS: Japan's share of original articles for basic medical science has
      increased in the last decade. On the other hand, its share of review articles was
      low and has remained stagnant in the same period.

PMID- 15477732
TI  - IgD myeloma with systemic amyloidosis with chest discomfort as an initial
      symptom.
AB  - A 53-year-old man was admitted to Keio University Hospital because of serious
      dyspnea and edema of the lower extremities. Eighteen months previously, the
      patient had complained of chest discomfort, and was then admitted for the first
      time to our hospital for evaluation of chest pain. Electrocardiography showed
      poor R wave progression in leads Vl through V4, and diffuse nonspecific ST
      segment and T wave abnormalities with low voltage. However, no definitive
      diagnosis could be made at this initial admission and a calcium-channel blocker
      was prescribed. Despite this treatment, the patient was readmitted with worsening
      dyspnea and lower extremity edema. The diagnosis of heart failure and nephritic
      syndrome was made at the second admission. In addition, immunoelectrophoresis
      showed a monoclonal IgD (lambda) M protein and increased plasma cells in the bone
      marrow, suggesting a diagnosis of multiple myeloma. The patient was thus given
      dexamethasone (20 mg per day for 4 days) intravenously, but his symptoms did not
      improve. Two weeks later, the patient deteriorated further with congestive heart
      failure and renal failure, and subsequently died of cardiac arrest with
      ventricular fibrillation. On autopsy, IgD (lambda)-positive plasma cell
      proliferation was found in the bone marrow, confirming the diagnosis of multiple
      myeloma. In addition, amyloid deposition was detected in various organs including
      the heart, kidneys, esophagus, duodenum, ileum, colon, tongue, and lungs. In
      particular, the weight of the heart was 650 g demonstrating a hypertrophic septum
      and amyloid deposition in the myocardium and even coronary arteries. In summary,
      the final diagnosis was IgD (lambda) multiple myeloma associated with systemic
      amyloidosis.

PMID- 15477733
TI  - Identifying diverse HIV risk groups among American Indian young adults: the
      utility of cluster analysis.
AB  - We demonstrate the utility of cluster analysis for identifying diverse HIV risk
      groups found in a community-based sample. Within a group of 706 American Indian
      young adults, we used cluster analysis to identify four profiles of HIV
      risk/protection. The High Efficacy/Low Risk cluster had high levels of
      knowledge/education, self-efficacy, and outcome expectations about HIV
      protection, with low levels of risk behaviors. Low Efficacy/Low Risk had low
      levels of HIV knowledge/education, self-efficacy, and outcome expectations, but
      high levels of perceived risk for HIV with low levels of HIV risk behaviors. Low
      Efficacy/Moderate Risk was similar to the previous group, but its members had
      moderately higher levels of several risk behaviors and higher condom use. Low
      Efficacy/High Risk had high rates of several high-risk behaviors such as
      exchanging sex for money or injection drug use. Validation analyses highlighted
      differences that can be useful for the development of preventive interventions.

PMID- 15477734
TI  - Surface potential and osteoblast attraction to calcium phosphate compounds is
      affected by selected alkaline hydrolysis processing.
AB  - This study examines the link(s) between the suspension behavior of calcium
      deficient apatites (CDAs) and biphasic calcium phosphate (BCP), as measured by
      the zeta-potential, with respect to both whole bone and osteoblasts. CDA is
      fabricated by hydrolyzing an acidic CaP such as dicalcium diphosphate dihydrate
      (DCPD; CaHPO4.2H2O) and has a structure and composition close to bone apatite.
      Sintering CDA results in the formation of BCP ceramics consisting of mixtures of
      hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP), with the HA/beta
      TCP weight ratio proportional to the Ca/P ratio of CDA. The choice of the base
      for the DCPD hydrolysis allows various ionic partial substitution of the formed
      CDA. Na for Ca partial substitution is of interest because of the resulting
      improvement in mechanical properties of the resulting BCP ceramics and NH4OH was
      used as a negative control. The zeta-potential was measured for these materials
      and the stability of the ceramic to bone interaction calculated. zeta-potential
      values decrease for CDA(NH4OH) versus CDA(NaOH) and increase for BCP(NH4OH)
      versus BCP(NaOH). While results of these analyses indicate that NH4OH and NaOH
      processed CDA and BCP will likely yield osteoblast attachment in vivo,
      differences in the zeta-potentials may explain varying degrees of cell
      attachment.

PMID- 15477735
TI  - Effect of lattice constant of zinc oxide on antibacterial characteristics.
AB  - Zinc oxide powders were heated in different atmospheres at 800 and 1400 degrees
      C, of which the characterization and the antibacterial activity were studied by X
      ray diffractometry and the measurement of the change in electrical conductivity
      with bacterial growth. The diffraction peaks corresponding to zinc oxide with
      hexagonal type structure were detected in all samples, which shifted in low-angle
      side with the increase in the oxidizability of atmosphere during heat-treatment.
      From the results of calculating lattice constants, a0 and c0, it was found that
      the value of c0 in hexagonal structure increased with the increase in the
      oxidizability of atmosphere. On the samples heated at 1400 degrees C, the changes
      of the c0 value were less than those at 800 degrees C. However, no change of the
      a0 value showed, irrespective of atmosphere and temperature. Hydrogen peroxide
      that contributes to the occurrence of antibacterial activity was found to
      generate from all samples, and the generation amount increased with the increase
      of c0 value; incidently the amount in the samples heated at 1400 degrees C was
      less than that at 800 degrees C. The antibacterial activity of zinc oxide
      increased with the increase of c0 value; that is, it was found that the value of
      c0 in crystal structure affected the antibacterial activity of zinc oxide.

PMID- 15477736
TI  - The effect of partially stabilized zirconia on the mechanical properties of the
      hydroxyapatite-polyethylene composites.
AB  - The effect of partially stabilized zirconia (PSZ) on the mechanical properties of
      the hydroxyapatite-high density polyethylene composites was studied by
      investigating the effect of hydroxyapatite and the simultaneous effect of
      hydroxyapatite and PSZ volume fractions on fracture strength, modulus of
      elasticity, and absorbed energy in the composite samples. The results showed a
      decrease in fracture strength, and absorbed energy with an increase in the volume
      fraction of hydroxyapatite content in the hydroxyapatite-polyethylene samples.
      Partial replacement of hydroxyapatite with PSZ particles was beneficial in the
      improvement of both the fracture strength and failure energy values in the
      composite samples. A transition from ductile to brittle behavior was observed as
      the volume fraction of ceramic filler particles increased in the samples.

PMID- 15477737
TI  - In vivo absorption of porous apatite- and wollastonite-containing glass-ceramic.
AB  - The behavior of porous apatite- and wollastonite-containing glass-ceramic (AW) in
      the bone marrow cavity was investigated. Cylinders of porous AW (4 mm in diameter
      and 20 mm long, mean porosity of 70% and mean pore diameter of 200 microm) were
      implanted into the bone marrow cavity of rabbit femurs, and analyzed by
      chronological radiograms and by scanning electron microscopy one, three, six, and
      12 months later. The pores of porous AW are interconnected and homogeneously
      distributed, and its compressive strength is nearly equal to that of human
      cancellous bone. Bone formed in the pores at the center of the material by one
      month and bonded to the material directly. The volume of newly formed bone in the
      material pores reached a peak at three months, and decreased gradually after six
      months. The trabecular structures of AW were gradually remodeled by newly formed
      bone, while AW-bone bonding was maintained during bone remodeling and material
      absorption. AW was absorbed continuously, and at six and 12 months the residual
      material corresponded to about 64 and 30% of the starting material, respectively.
      Porous AW may therefore be useful as an absorbable bone substitute.

PMID- 15477738
TI  - Synthesis and characterization of partially biodegradable and thermosensitive
      hydrogel.
AB  - A partially biodegradable and thermosensitive hybrid hydrogel network (DAN
      series) based on dextran-allylisocyanate (Dex-AI) and poly(N-isopropylacrylamide)
      (PNIPAAm) was synthesized via UV photocrosslinking. These hybrid hydrogels were
      characterized in terms of their chemical structure, thermal, mechanical,
      morphological and temperature-induced swelling properties. The effect of the
      composition ratio of Dex-AI to PNIPAAm on such properties were examined. The
      differential scanning calorimetry data show that this Dex-AI/PNIPAAm hybrid
      network has an increased lower critical solution temperature (LCST) and glass
      transition temperature (Tg) with an increase in the Dex-AI content. The interior
      morphology of these hybrid hydrogels revealed a decreased porous microstructure
      with an increase in the Dex-AI content in the hybrid network. Furthermore, if the
      Dex-AI composition became too high, a distinctive network structure with two
      different microporous structures appeared. The mechanical properties of these
      hybrid hydrogels also increased with an increase in the Dex-AI content. The
      temperature dependence of the swelling ratio, the deswelling kinetics as well as
      the reswelling kinetics was also characterized by gravimetric method. When
      comparing with a normal PNIPAAm hydrogel, these Dex-AI/PNIPAAm hybrid networks,
      due to the presence of Dex-AI moiety, also show improved temperature-induced
      intelligent properties, such as the faster and controllable response dynamics,
      which may find promising applications in a wide variety of fields, such as
      biomedical and bioengineering fields.

PMID- 15477739
TI  - Novel PEEK-WC membranes with low plasma protein affinity related to surface free
      energy parameters.
AB  - There has been growing interest in innovative materials with specific physico
      chemical properties that provide an improved blood/cell compatibility. In this
      paper we evaluated the performance of new membranes prepared from a modified
      polyetheretherketone (PEEK-WC) contacting human plasma proteins. These membranes
      were prepared by using the phase inversion technique. Membrane wettability and
      affinity to proteins were evaluated by means of contact angle experiments,
      roughness measurements, and quantitative UV analysis. The energy parameters of
      membrane surfaces were determined according to Good, van Oss and Chaudhury's
      theory. The extent of human albumin, fibrinogen and immunoglobulin G adsorption
      was related to quantitative expressions of the membrane surface hydrophilicity:
      the base parameter of surface free energy and the free energy of interfacial
      interaction. The performance of PEEK-WC membranes was compared to that of
      commercial membranes, which conventionally are used in biomedical applications.
      The experimental results showed a reduction of protein adsorption on PEEK-WC
      membranes with respect to other commercial membranes. The low protein affinity of
      PEEK-WC membranes is due to the intrinsic physico-chemical characteristics of the
      polymeric material which makes these membranes interesting for potential use in
      biomedical applications.

PMID- 15477740
TI  - Development of a beta-type Ti-12Mo-5Ta alloy for biomedical applications:
      cytocompatibility and metallurgical aspects.
AB  - Ti-based biocompatible alloys are especially used for replacing failed hard
      tissue. Some of the most actively investigated materials for medical implants are
      the beta-Ti alloys, as they have a low elastic modulus (to inhibit bone
      resorption). They are alloyed with elements such as Nb, Ta, Zr, Mo, and Fe. We
      have prepared a new beta-Ti alloy that combines Ti with the non-toxic elements Ta
      and Mo using a vacuum arc-melting furnace and then annealed at 950 degrees C for
      one hour. The alloy was finally quenched in water at room temperature. The Ti
      12Mo-5Ta alloy was characterised by X-ray diffraction, optical microscopy, SEM
      and EDS and found to have a body-centred-cubic structure (beta-type). It had a
      lower Young's modulus (about 74 GPa) than the classical alpha/beta Ti-6Al-4V
      alloy (120 GPa), while its Vickers hardness remained very high (about 303 HV).
      This makes it a good compromise for a use as a bone substitute. The
      cytocompatibility of samples of Ti-12Mo-5Ta and Ti-6Al-4V titanium alloys with
      various surface roughnesses was assessed in vitro using organotypic cultures of
      bone tissue and quantitative analyses of cell migration, proliferation and
      adhesion. Mechanically polished surfaces were prepared to produce unorientated
      residual polished grooves and cells grew to a particularly high density on the
      smoother Ti-12Mo-5Ta surface tested.

PMID- 15477741
TI  - Bioactivity of degradable polymer sutures coated with bioactive glass.
AB  - Novel bioactive materials have been prepared by coating violet resorbable Vicryl
      sutures with a bioactive glass powder derived from a co-precipitation method. Two
      techniques have been chosen for the composite preparation: pressing the sutures
      in a bed of glass powder and slurry-dipping of sutures in liquid suspensions of
      bioactive glass powders. The uniformity and thickness of the coatings obtained by
      the two methods were compared. The bioactivity of the sutures with and without
      bioactive glass coating was tested by soaking in an inorganic acellular simulated
      body fluid (SBF). The composite sutures were characterised by XRD, SEM and FTIR
      analyses before and after soaking in SBF solution to assess the formation of
      hydroxyapatite on their surfaces, which is a qualitative measure of their
      bioactivity. The possible use of bioactive sutures to produce tissue engineering
      scaffolds and as reinforcement of resorbable calcium phosphates is discussed.

PMID- 15477742
TI  - The synthesis and characterization of polymer coated iron oxide microspheres.
AB  - For biomedical applications drug carrying polymers are coated around magnetic
      iron oxide particles to form microspheres. In the present study, the iron oxide
      powder was ball milled. Microspheres were then synthesized by solvent
      evaporation, resulting in iron oxide particles encapsulated in a polymer and drug
      coating. Various parameters, such as the duration of milling and agitation speed
      as well as the polymer concentration were varied. A milling time of 72 h was
      found to yield a small size and narrow size distribution of particles; the
      average particle size was about 600 nm. Measurements of the change in grain size
      and the magnetic properties of the powder with milling time were performed. It
      was determined that the size of the microspheres was not sensitive to the initial
      particle size, but it could be decreased by variation of agitation speed or
      polymer concentration. The agitation speed and polymer concentration of 400 rpm
      and 0.04 g poly(l-lactic acid) in 8 g dicholoromethane, respectively, was found
      to yield small, spherical microspheres with a narrow size distribution. The
      surface morphology and magnetic properties of the microspheres was also analyzed.

PMID- 15477743
TI  - Evaluation of the effect of the concentration of plasticizer di(2-ethylhexyl)
      phthalate on the quantity of residual monomer vinyl chloride in PVC chest
      drainage tubes.
AB  - The effect of amount of plasticizer di(2-ethylhexyl) phthalate (DEHP) amount on
      the amount of residual monomer vinyl chloride (VC) was determined in samples of
      plasticised polyvinyl chloride (PVC) with different concentration of plasticiser
      (22.32-33.05%), before and after sterilisation by a titrimetric method. The
      titrimetric method was used to determine the VC concentration in a KMnO4 solution
      where the samples were kept immersed under the same conditions for 2 h. The
      influence of PVC film extracts with different amounts of DEHP on mouse fibroblast
      cells L-929 in a culture medium was evaluated by using quantitative tests: the
      amount of cells (protein determination), viability (MTT test) and proliferation
      (incorporation of bromodeoxyuridine (BrDU). The amount of vinyl chloride before
      and after heat sterilisation at 120 degrees C for 30 min was found to be almost
      the same for all samples and without any dependence on the concentration of DEHP.
      The extracts of the PVC films which were tested have no toxic effect on cells in
      a culture medium.

PMID- 15477744
TI  - A comparative investigation of biodegradable polyhydroxyalkanoate films as
      matrices for in vitro cell cultures.
AB  - The paper describes the production and investigation of flexible films made of
      high-purity polyhydroxyalkanoates (PHAs)--polyhydroxybutyrate [poly-(3HB)] and
      poly-3-hydroxybutyrate-co-poly-3-hydroxyvalerate [poly(3HB-co-3HV)], containing 4
      30 mol % hydroxyvalerate. Poly(3HB-co-3HV) films have a more porous structure
      than poly-(3HB) films, which are more compact, but their surface properties, such
      as wettability and surface and interface energies, are the same. Sterilisation of
      the PHA films by conventional methods (heat treatment and gamma-irradiation) did
      not impair their strength. Cells cultured on PHA films exhibited high levels of
      cell adhesion. Cell morphology, protein synthesis and DNA synthesis were
      estimated by extent of 3H-thymidine incorporation into the animal cell cultures
      of various origins (fibroblasts, endothelium cells, and isolated hepatocytes) in
      direct contact with PHAs. The investigation showed that this material can be used
      to make matrices for in vitro proliferous cells. The investigated properties of
      poly-(3HB) and poly(3HB-co-3HV) films proved to be fundamentally similar.

PMID- 15477745
TI  - Porcine collagen crosslinking, degradation and its capability for fibroblast
      adhesion and proliferation.
AB  - Porcine dermal collagen permanently crosslinked with hexamethylene diisocyanate
      was investigated for its suitability as a dermal tissue engineering matrix. It
      was found that the chemically crosslinked collagen had far fewer free lysine
      groups per collagen molecule than did the uncrosslinked matrix. The ability of
      the matrix to support human primary fibroblast outgrowth from explants was
      compared for matrices that had been presoaked in various solutions, including
      fibroblast media, cysteine and phosphate buffered saline (PBS). It was found that
      superior cell outgrowth was obtained after soaking with fibroblast media and PBS.
      The fibroblast attachment properties of the matrix were compared against tissue
      culture plastic and PET. The collagen matrix showed the least amount of cell
      retention compared to the other to matrices, however, the general trends were
      similar for all three scaffolds. Longer term cultures on the collagen showed
      fibroblasts covering the matrix stacking up on each other and bridging natural
      hair follicles. However, it was also observed that the fibroblasts were not able
      to penetrate into the matrix structure. This was believed to result from the
      chemical crosslinking, as shown by the resistance of the matrix to degradation by
      collagenases.

PMID- 15477750
TI  - Eutetrarhynchid cestodes from Atlantic and Mediterranean elasmobranch fishes,
      with the description of two new species of Dollfusiella Campbell & Beveridge,
      1994 and redescriptions of Prochristianella papillifer (Poyarkoff, 1909) Dollfus,
      1957 and Parachristianella trygonis Dollfus, 1946.
AB  - Dollfusiella elongata n. sp. is described from the spiral valves of Rhinobatos
      rhinobatos (Linnaeus) and R. cemiculus Geoffroy St-Hilaire off the coast of
      Tunisia, while D. aculeata n. sp. is described from the spiral valves of Dasyatis
      pastinaca (Linnaeus) off the western coast of France, Dasyatis tortonesei Capape
      off the coast of Tunisia and Dasyatis chrysonota (Smith) var. marmorata off the
      coast of Senegal. A redescription of Dollfusiella spinifer (Dollfus, 1969)
      Campbell & Beveridge, 1994 is included based on the type-specimens from
      Myliobatis aquila (Linnaeus) from the Mediterranean coast of France.
      Prochristianella papillifer (Poyarkoff, 1909) Dollfus, 1957 is redescribed from
      specimens from Dasyatis pastinaca off Tunisia and the scolex and mature segments
      are described for the first time. Parachristianella trygonis Dollfus, 1946 is
      redescribed from Dasyatis pastinaca off the coast of France and Dasyatis
      tortonesei off Tunisia, with the mature and gravid segments being described for
      the first time. Parachristianella monomegacantha Kruse, 1959 is reported for the
      first time from the elasmobranchs Dasyatis pastinaca , Myliobatis aquila ,
      Rhinobatos cemiculus and R. rhinobatos . Definitions of the related genera
      Dollfusiella Campbell & Beveridge, 1994 and Prochristianella Dollfus, 1946 are
      revised. Prochristianella spinulifera Beveridge & Jones, 2000 is transferred to
      Dollfusiella as D. spinulifera n. comb. New combinations proposed formally for
      the first time are: D. aetobati (Beveridge, 1990) n. comb., D. bareldsi
      (Beveridge, 1990) n. comb., D. lineata (Linton, 1909) n. comb., D. litocephalus
      (Heinz & Dailey, 1974) n. comb., D. macrotrachelus (Heinz & Dailey, 1974) n.
      comb., D. michiae (Southwell, 1929) n. comb., D. musteli (Carvajal, 1974) n.
      comb., D. schmidti (Heinz & Dailey, 1974) n. comb. and D. vooreemi (Sao Clemente
      & Gomes, 1989) n. comb. The type-specimens of Prochristianella tenuispinis
      (Linton, 1890) Dollfus, 1946 were re-examined and the species is transferred to
      Dollfusiella as D. tenuispinis (Linton, 1890) n. comb. Features of known species
      of Dollfusiella are presented in tabular form.

PMID- 15477751
TI  - Four new species of Gyrodactylus von Nordmann, 1832 (Monogenea, Gyrodactylidae)
      on gobiid fishes: combined DNA and morphological analyses.
AB  - Four Gyrodactylus species parasitising four closely related gobiid species in
      European coastal waters were studied and compared with G. arcuatus Bychowsky
      sensu Bychowsky & Poljansky (1953) from Gasterosteus aculatus . These were G.
      gondae n. sp. from Pomatoschistus minutus and P. lozanoi , G. flavescensis n. sp.
      from Gobiusculus flavescens , G. arcuatoides n. sp. from P. minutus and G.
      branchialis n. sp. from P. microps. Combined molecular and morphological
      analyses, as well as morphometric and statistical methods, were used. The ssrRNA
      V4 region and the complete ITS rDNA region were sequenced. Genetically the four
      new species are clearly distinct from G. arcuatus . From a morphological point of
      view, the haptoral hard parts of G. gondae n. sp., G. flavescensis n. sp. and G.
      arcuatoides n. sp. are related to those of G. arcuatus, while these parts of G.
      branchialis n. sp. are different, but related to those of G. quadratidigitus
      Longshaw, Pursglove & Shinn, 2003. For the latter two species, a new species
      group is formed. The V4 and ITS sequence analyses, however, indicate a close
      relationship between G. branchialis and the three G. arcuatus-like species.

PMID- 15477752
TI  - Terminology of the sucker-like organs of the scolex of trypanorhynch cestodes.
AB  - The literature associated with descriptions and definitions of the sucker-like
      attachment organs in trypanorhynchs, termed either bothria or bothridia, is
      reviewed. There are descriptions of 14 trypanorhynch species representing 10
      families. In none of these trypanorhynchs was a membrane separating the
      attachment organ from the scolex parenchyma described, one of the definitions
      used to distinguish bothria from bothridia. Transmission electron microscopy of
      the bothria of the trypanorhynch species Nybelinia queenslandensis Beveridge &
      Jones, 1998 (Tentaculariidae) and Otobothrium mugilis Hiscock, 1954
      (Otobothriidae) also failed to show any membranous structure separating the
      surface of the attachment organ from the cestode parenchyma. The sucker-like
      attachment organs of trypanorhynchan cestodes appear, therefore, to be bothria
      rather than bothridia. As a result, changes in the terminology of related
      features of the scolex are proposed here. Henceforth, the pars bothridialis
      should be referred to as the pars bothrialis and the bothridial pits should be
      referred to bothrial pits.

PMID- 15477753
TI  - A redescription of Cylicocyclus adersi Boulenger, 1920 (Nematoda: Strongyloidea:
      Cyathostominae) parasitic in equids.
AB  - As part of a revision of the systematics of the Cyathostominea of equids, we
      determined that the single type-specimen of Cylicocyclus adersi Boulenger, 1920
      is missing and a modern description of this rare species parasitic in donkeys
      Equus asinus L. and zebras E. burchelli (Gray) and E. zebra L. is not available.
      Systematists at a workshop on the systematics of the Cyathostominea of horses,
      convened on August 11, 1997 in Sun City, South Africa, listed C. adersi as a
      species inquirenda . Herein, we provide a redescription of C. adersi and propose
      a neotype for the species. The distinctive shape of the buccal capsule of C.
      adersi , with a relatively tiny 'hoop-like thickening' at its base, a relatively
      small oesophageal funnel with a thick cuticular lining, and a short, but
      distinct, dorsal gutter readily distinguishes this species from other large
      species of Cylicocyclus Ihle, 1922.

PMID- 15477754
TI  - Redescription of larva, nymph and adults of Ixodes (I .) loricatus Neumann, 1899
      (Acari: Ixodidae) based on light and scanning electron microscopy.
AB  - Ticks of the genus Ixodes are poorly known in the Neotropical zoogeographical
      region, from where only 45 species have been recorded. In Brazil, the genus is
      currently represented by eight species, four of which are known only from this
      country. This paper presents a redescription of all active stages in the life
      cycle of I. loricatus , based on optical and scanning electron microscopy. In
      addition, the relationship of I. loricatus to other Neotropical Ixodes is
      presented and discussed.

PMID- 15477755
TI  - Comparison of morphological characters in Irish and English populations of the
      acanthocephalan Pomphorhynchus laevis (Muller, 1776).
AB  - Pomphorhynchus laevis is believed on ecological evidence to exist as three
      strains in the British Isles. However, the strains have never been shown to be
      capable of being distinguished using morphological characters. A morphological
      comparison was made between a sample of P. laevis from Salmo trutta in L. Feeagh
      in the west of Ireland and a sample from Leuciscus cephalus in R. Culm in the
      south of England. The length and width of the trunk, neck, bulb, proboscis and
      hooks were measured. The number of hooks per row, the number of rows and the
      positions of the stoutest and longest hooks were also recorded. A Principal
      Components Analysis based on the morphological measurements confirmed the
      separation of the two populations and showed that two characters successfully
      identified the populations: the position of the stoutest hook and the ratio of
      numbers of anterior to posterior hooks.

PMID- 15477756
TI  - Cytotoxicity of HSVtk and hrTNF-alpha fusion genes with IRES in treatment of
      gastric cancer.
AB  - The efficacy of the suicide gene therapy by using the herpes simplex virus
      thymidine kinase/ganciclovir (HSVtk/GCV) system for the treatment of cancer is
      limited because of the insufficient gene transfer and the low killing activity.
      To enhance the antitumor activity, we probed into whether recombinant ritroviral
      expression vector PLXSN expressing both HSVtk and TNF-alpha genes could
      potentiate the destruction of SGC7901. The PL(tk-TNF-alpha)SN harboring HSVtk and
      TNF-alpha genes in sequence was constructed with a bicistronic unit including the
      internal ribosomal entry site, the recombinant retroviruses were transferred into
      SGC7901 cells by lipofectamine, and pEGFP and Western blot analysis were used to
      detect the expression of fusion genes in transfected SGC7901 cells, and then
      apoptosis of the transfected cells were detected by using the TdT-mediated dUTP
      nick end labeling, flow cytometric analysis and transmission electron microscopy.
      In vitro study, the transfected gastric cancer cells were maintained in the GCV
      contained medium, to assay the cell killing effect and bystander effect. In vivo
      experiments, retroviral serum plasmids were transfected into tumor-bearing nude
      mice, to observe the changes of tumor volumes and survival of the mice. In vitro
      there was no significant difference of cell survival rate between the three
      groups. However, in vivo results showed that tk/GCV, tk-TNF-alpha/GCV and TNF
      alpha could inhibit the tumor growth, and the obvious anti-tumor effect was shown
      in tk-TNF-alpha/GCV group, and TNF-alpha obviously enhanced the anti-tumor effect
      in vivo. The pathologic examination showed necrosis of the cancer in the treated
      groups.

PMID- 15477757
TI  - Differentially expressed genes in pancreatic ductal adenocarcinomas identified
      through serial analysis of gene expression.
AB  - Serial analysis of gene expression (SAGE) is a powerful tool for the discovery of
      novel tumor markers. The publicly available online SAGE libraries of normal and
      neoplastic tissues (http://www.ncbi.nlm.nih.gov/SAGE/) have recently been
      expanded; in addition, a more complete annotation of the human genome and better
      biocomputational techniques have substantially improved the assignment of
      differentially expressed SAGE "tags" to human genes. These improvements have
      provided us with an opportunity to re-evaluate global gene expression in
      pancreatic cancer using existing SAGE libraries. SAGE libraries generated from
      six pancreatic cancers were compared to SAGE libraries generated from 11 non
      neoplastic tissues. Compared to normal tissue libraries, we identified 453 SAGE
      tags as differentially expressed in pancreatic cancer, including 395 that mapped
      to known genes and 58 "uncharacterized" tags. Of the 395 SAGE tags assigned to
      known genes, 223 were overexpressed in pancreatic cancer, and 172 were
      underexpressed. In order to map the 58 uncharacterized differentially expressed
      SAGE tags to genes, we used a newly developed resource called TAGmapper
      (http://tagmapper.ibioinformatics.org), to identify 16 additional differentially
      expressed genes. The differential expression of seven genes, involved in multiple
      cellular processes such as signal transduction (MIC-1), differentiation (DMBT1
      and Neugrin), immune response (CD74), inflammation (CXCL2), cell cycle (CEB1) and
      enzymatic activity (Kallikrein 6), was confirmed by either immunohistochemical
      labeling of tissue microarrays (Kallikrein 6, CD74 and DMBT1) or by RT-PCR (CEB1,
      Neugrin, MIC1 and CXCL2). Of note, Neugrin was one of the genes whose previously
      uncharacterized SAGE tag was correctly assigned using TAGmapper, validating the
      utility of this program. Novel differentially expressed genes in a cancer type
      can be identified by revisiting updated and expanded SAGE databases. TAGmapper
      should prove to be a powerful tool for the discovery of novel tumor markers
      through assignment of uncharacterized SAGE tags.

PMID- 15477758
TI  - Celecoxib inhibits angiogenesis by inducing endothelial cell apoptosis in human
      pancreatic tumor xenografts.
AB  - Previous studies suggest that antagonists of cyclooxygenases 1 and 2 (COX-1, -2)
      inhibit angiogenesis in tumor xenografts, but the molecular mechanisms involved
      remain unclear. Here we characterized the effects of non-selective (indomethacin)
      and selective (NS398, celecoxib) cyclooxygenase inhibitors on parameters of
      angiogenesis in human pancreatic adenocarcinoma cells. COX-1 expression was
      constitutive in 9/9 pancreatic cancer cell lines, whereas COX-2 and cytosolic
      phospholipase A2 (cPLA2) expression were observed in 4/9 cell lines (BxPC3,
      Capan2, Cfpac1, and L3.6 pl). Production of the COX product, prostaglandin E2,
      correlated with expression of cPLA2 and COX-2 and was blocked by non-steroidal
      anti-inflammatory drugs (NSAIDs, indomethacin or NS398). In contrast to the
      findings of others, neither indomethacin nor NS398 affected tumor cell secretion
      of angiogenic factors (VEGF, bFGF, IL-8) at concentrations that produced maximal
      inhibition of PGE2 production, and higher concentrations increased angiogenic
      factor production. We also studied the effects of celecoxib in orthotopic L3.6 pl
      xenografts. Immunofluorescence analyses revealed high-level expression of COX-2
      in endothelial cells in L3.6 pl xenografts that increased following therapy with
      celecoxib, whereas the tumor cells expressed uniformly low levels of COX-2.
      Celecoxib did not decrease tumor-associated VEGF levels in orthotopic human L3.6
      pl xenografts, but the drug did decrease tumor microvessel density (MVD) and
      increase apoptosis in tumor-associated endothelial cells in a dose-dependent
      fashion. Together, our results demonstrate that the anti-angiogeneic effects of
      NSAIDs in human pancreatic cancer cells are exerted via direct effects on
      endothelial cells.

PMID- 15477760
TI  - Genomic instability is associated with lack of telomerase activation in ovarian
      cancer.
AB  - INTRODUCTION: Malignant cells are capable of an unlimited number of cell
      divisions, either through production of telomerase, or through the alternate
      lengthening of telomere (ALT) mechanism. Yeast cells with genomic instability
      have been shown to survive in the absence of telomerase by increased
      recombination events. We hypothesized that ovarian cancers with high
      microsatellite instability (MSI-H) are more likely to lack telomerase activation.
      METHODS: We examined 104 invasive ovarian cancers for MSI with six microsatellite
      markers (BAT25, BAT26, D5S346, D2S123, D17S250 and NME1). Telomerase activity was
      determined with ELISA, and its subunits human telomerase reverse transcriptase
      (hTERT) and human telomerase RNA (hTR) by RT-PCR. Statistical analysis was
      performed with Chi-square and p<0.05 was considered significant. RESULTS:
      Telomerase activity was detected in 79 samples (76%). The hTERT subunit was
      detected in 85% of samples, and hTR was found in all ovarian cancers. Presence of
      hTERT was positively associated with telomerase activity (p=0.001). High MSI (MSI
      H), defined as two or more positive markers, was detected in 15% of ovarian
      cancers; low MSI (MSI-L), defined as having only one positive marker, was found
      in 13%; the remaining 72% were microsatellite stable (MSI-S). Telomerase activity
      was detected in 83% of MSI-S and 79% of MSI-L tumors, but only 40% of MSI-H
      tumors (p=0.002). Interestingly, hTERT was similar in all three groups (range 73
      84%, p=0.59), demonstrating that the presence of hTERT transcript was not the
      only determinant of telomerase activity in MSI-H tumors. CONCLUSIONS: Ovarian
      cancers with high MSI are more likely to propagate without the need to produce
      telomerase.

PMID- 15477759
TI  - High frequency of common deletion (4981 bp) in mitochondrial DNA in
      nasopharyngeal carcinoma and its correlation with patient age and clinical
      stages.
AB  - Mitochondrial DNA (mtDNA) has a high mutation rate due at least in part to a lack
      of protective histones and an inefficient DNA repair system. The most frequently
      change in mtDNA is the so-called Common Deletion (CD), which accumulates in
      patients with heteroplasmic mtDNA mutations and in normal individuals during
      aging. In this study, wild type mtDNA (WT-mtDNA) and mitochondrial DNA with CD
      (CD-mtDNA) were quantitatively analyzed in different nasopharynx lesions. A novel
      type of CD-mtDNA (4981 bp) was detected significantly higher in nasopharyngeal
      carcinoma (NPC) (93%, 54/58) than in nasopharyngitis (60%, 28/47) and the paired
      white blood cells (WBC) (26%, 8/31). The ratio of CD-mtDNA to WT-mtDNA in NPC
      (0.000625, median) was ten times that in nasopharyngitis (0.000064, median)
      (P=0.003), and was significantly higher than that in paired WBC (0.000000,
      median) (P=0.000). The CD/WT-mtDNA ratio was 0.000564 (quartile range, 0.000184
      0.000919) in late stage NPC, which was nearly three times the ratio in early
      stage NPC (0.000164, quartile range, 0.000042-0.000353) (P=0.015, Mann-Whitney
      Test). In NPC patients with ages <48yrs (mean age), the ratio of CD-mtDNA to WT
      mtDNA was 0.000625, which was nearly ten times that in NPC patients with
      ages<48yrs (0.000064) (P=0.005, Mann-Whitney Test). This is the first
      quantitative study of CD-mtDNA mutations in NPC, which provides evidences that CD
      mtDNA mutation might be involved in the development and progression of NPC.

PMID- 15477761
TI  - Cyclin proteolysis and CDK inhibitors: two redundant pathways to maintain genome
      stability in mammalian cells.
AB  - Cyclin-dependent kinases (CDKs) are regulated by cyclin proteolysis and CDK
      inhibitors (CKIs) during mitotic exit and G(1) phase in yeast and Drosophila, and
      disruption of both regulatory pathways leads to genomic instability. Our study
      using mouse cell lines that constitutively express a stabilized mutant of cyclin
      A revealed that three CKIs, p21, p27, and Rb-related p107, are responsible for
      cyclin proteolysis-independent inactivation of CDK during mitotic exit and G(1).
      Enforced expression of cyclin A in the cells lacking all three CKIs induced rapid
      tetraploidization. Thus, the redundant pathways consisting of cyclin proteolysis
      and CKIs control CDK activity during mitotic exit and contribute to maintenance
      of genome stability in mammalian cells.

PMID- 15477762
TI  - Specific and redundant functions of histone deacetylases in regulation of cell
      cycle and apoptosis.
AB  - Inappropriate control of expression of genetic information is the cause of many
      forms of cancer. Aberrant transcriptional repression by recruitment of histone
      deacetylases (HDACs) is a key step in pathogenesis of myeloid leukemia. We
      recently reported that development of colonic cancer involves alterations in the
      transcriptional repression machinery by increased expression of HDAC2 upon loss
      of the APC tumor suppressor. Increased expression of HDAC2 is essential for
      prevention of apoptosis of HT-29 colonic cancer cells. We now discuss whether
      HDAC2 also plays a role for aberrant cell cycle regulation and expression of the
      p21(Cip/Waf) cell cycle inhibitor. Whereas inhibition of HDACs by valproic acid
      or trichostatin A increases p21 expression, selective interference with HDAC2 by
      siRNA transfection or reconstitution of wildtype APC does not affect p21
      expression. Likewise, treatment of HT-29 cells with the HDAC inhibitor valproic
      acid leads to a moderate inhibition of cell cycle progression in the G1 phase
      whereas interference with HDAC2 expression does not. Thus, HDAC2 appears to serve
      a preferential role in the prevention of apoptosis and not in cell cycle control
      similar to the specific importance of HDAC1 for cell cycle regulation or HDAC 9
      for the stress response of the heart.

PMID- 15477767
TI  - [Epidemiological aspects of metabolic syndrome.].
AB  - During 15 years criteria of metabolic syndrome has undergone definite changes.
      According to Adult Treatment Panel III of National Cholesterol Education Program
      metabolic syndrome is diagnosed in the presence of 3 of 5 following signs: waist
      circumference>/=102 or small i, Ukrainian88 cm in men and women, respectively;
      triglycerides small i, Ukrainian150 mg/dl, high density lipoprotein cholesterol
      <39 mg/dl; blood pressure >/=130/85 mm Hg and fasting blood glucose >/=110 mg/dl.
      Metabolic syndrome is widely spread in populations. Its prevalence ranges from
      10.6% in China to 24% in USA and is closely related to life style and age. In a
      cohort of subjects with history of hypertension at least 5 years and diabetes
      type2 metabolic syndrome was found in 64 and 88%, respectively. Metabolic
      syndrome has rather high atherogenic potential and is associated with incidence
      of ischemic heart disease 2.6-3.0, ischemic heart disease mortality - 2.9-4.2,
      total mortality - 1.9-2.1 times higher compared with other diseases.

PMID- 15477768
TI  - [On the possible prooxidant role of insulinemia in formation of metabolic
      syndrome in men and women.].
AB  - Levels of basal insulinemia, malondialdehyde (an index of oxidative stress) and
      some metabolic parameters were studied in 143 men and 83 women aged 48.3+/-0.7
      years with incomplete metabolic syndrome: hypertension, abdominal obesity,
      dyslipoproteinemia with normoglycemia. Basal insulinemia correlated significantly
      with malondialdehyde levels both in men and women. Slose relationship was also
      found between basal insulinemia and waist circumference.

PMID- 15477769
TI  - [Effect of moxonidine on parameters of lipid metabolism in patients with
      metabolic syndrome.].
AB  - AIM: To compare effects of moxonidine and lisinopril on parameters of lipid
      metabolism in patients with metabolic syndrome. METHODS: Moxonidine (0.2-04
      mg/day) and lisinopril (10-20 mg/day) were given to 25 and 24 patients,
      respectively. Blood pressure, heart rate, parameters of lipid profile and fasting
      blood glucose were measured before and after 12 weeks of treatment. RESULTS:
      Antihypertensive efficacy of 2 drugs was similar. No changes of lipid profile
      occurred in lisinopril treated patients while significant elevation of high
      density lipoprotein cholesterol and tendency to lowering of triglyceride level
      were observed in moxonidine group. CONCLUSION: Therapy with moxonidine was
      associated with favorable changes of lipid profile.

PMID- 15477770
TI  - [First experience with the use of bone marrow stem cells for regeneration therapy
      of ischemic heart disease.].
AB  - AIM: To elucidate feasibility of the use of autologous bone marrow stem cells in
      candidates to myocardial revascularization- patients with ischemic heart disease
      and cardiosclerosis after myocardial infarction. METHODS: Between January 2003
      and January 2004 25 men aged 56.3+/-5.4 years with ischemic heart disease were
      subjected to cell therapy including 4 patients with heart failure and 5 - with
      acute coronary syndrome. Subgroup of patients with postinfarction cardiosclerosis
      consisted of 16 men satisfying the following criteria: (1) history of myocardial
      infarction with scar formation; (2) class III-IV angina; (3) presence of
      indications for endovascular or surgical intervention on coronary arteries. Study
      protocol included clinical examination, coronary angiography; dobutamine stress-,
      contrast- and tissue echocardiography with assessment of segmental myocardial
      perfusion, systolic and diastolic left ventricular function. RESULTS: There were
      no complications during bone marrow sampling and administration of cells. All
      patients were restudied 1 month after transplantation. Improvement of clinical
      state without complications and adverse effects of the procedure noted in all
      patients was associated with lowering of mean angina class (from 3.4 to 1.4,
      p<0.05); decrease of NYHA heart failure class (from 3.1 to 1.5); rise of left
      ventricular ejection fraction (from 42.9 to 56.3%); decrease of average number of
      asynergic segments (from 5.3+/-0.7 to 2.1+/-0.3, p<0.01). Systolic velocity
      before intervention was 2.3 cm/s, after procedure in segments subjected to
      isolated revascularization it increased up to 4.8 cm/s, while in those subjected
      to revascularization combined with administration of stem cells - up to 6.2 cm/s.
      Contrast echocardiography in 9 patients demonstrated augmented myocardial
      perfusion in regions exposed to cell therapy. CONCLUSION: Transplantation of
      autologous bone marrow stem cells to ischemic heart disease patients - candidates
      for myocardial reperfusion - turned out to be safe and well tolerated procedure.
      Combination of myocardial revascularization with administration of stem cells
      into regions of postinfarction scars was associated with improvement of total and
      local myocardial contractility and normalization of left ventricular diastolic
      filling. Cell therapy facilitated augmentation of myocardial perfusion.

PMID- 15477771
TI  - [Assessment of antianginal and antiischemic effect of trimetazidine and its
      effects on myocardial perfusion in patients with ischemic heart disease and
      stable angina.].
AB  - AIM: To assess antianginal and antiischemic effects of trimetazidine and its
      action on myocardial perfusion in patients with ischemic heart disease and stable
      angina. MATERIAL: Open trimetazidine was given for 3 months to 53 nitroglycerine
      and beta-blocker treated men aged 47-69 (mean age 60.2+/-0.85) years with
      ischemic heart disease and stable angina. Stenoses of 1-3 main coronary arteries
      were found at angiography in 37 of these patients. METHODS: Registration of
      frequency of anginal attacks and nitroglycerine consumption, treadmill exercise
      tests and 24-hour ECG monitoring, assessment of severity of myocardial perfusion
      defects by scintigraphy with (99m)Tc MIBI were used for elucidation of treatment
      efficacy. RESULTS: After 3 months number of anginal attacks per week decreased
      from 9.3+/-0.6 to 4.8+/-05% (-48%, p<0.001), weekly nitroglycerine consumption
      fell from 9.9+/-0.8 to 4.6+/-0.6 pills (-53%, p<0.001), time to ST-segment
      depression during exercise on treadmill increased from 6.4+/-0.4 to 7.7+/-0.5 min
      (+16.9%, p<0.001) and total work performed increased from 7.8+/-0.4 to 9.2+/-0.5
      METS (+15.2%, p<0.001). According to 24-hour ECG monitoring numbers of episodes
      of painful and painless ischemia decreased from 4.1+/-0.9 to 1.9+/-0.7 (-56.3%,
      p<0.002) and their overall duration shortened from 24.3+/-7.0 to 10.6+/-3.9 min
      (+56.3%, p<0.02). Analysis of heart rate variability revealed significant
      augmentation of SDNN in 77.8% of patients (from 130.0+/-6.9 to 145+/-8.1,
      p<0.05). Severity and extent of myocardial perfusion defects decreased in 87.5%
      of patients by 24,2% (from 476.1+/-78.5, p<0.01) and 20.3% (from 19.7+/-2.4 to
      15.7+/-2.0, p<0.01), respectively. CONCLUSION: The use of trimetazidine as
      complimentary therapy to nitrates and beta-blockers in patients was associated
      with additional antianginal and antiischemic effects and improvement of
      myocardial perfusion.

PMID- 15477772
TI  - [The study of cerebral oxygenation and central hemodynamics in patients with
      ischemic heart disease at rest and during physical effort.].
AB  - Cerebral oxygenation (rSO(2)) in the region of sagittal sinus and main
      hemodynamic parameters were measured in 112 patients with ischemic heart disease
      and class II-III angina. Four groups of patients were distinguished according to
      degree of rSO(2) lowering. Hemodynamics and oxygen transport function of the
      blood were proportionally related to degree of rSO(2) lowering. Normal rSO(2)
      (>70%) and degree lower (70-61%) was associated with predicted (desirable)
      cerebral blood flow. Lower rSO(2) values (60-50%) were accompanied with increased
      oxygen utilization (by 20-25%). Critical rSO(2) lowering (below 50%) was
      associated with>/=75% rise of oxygen utilization what was indicative of decreased
      brain blood flow and cerebral ischemia.

PMID- 15477773
TI  - [Comparison of various methods of assessment of heart rate variability including
      simple cardiovascular reflex tests as predictors of sudden cardiac death after
      myocardial infarction.].
AB  - Long term heart rate variability is used for prediction of sudden cardiac death
      (SD). There are simpler methods of assessment of autonomic cardiac control -
      registration of heart rate response to reflex tests and determination of heart
      rate variability (HRV) on short ECG recordins. Comparative value for prognosis of
      SD after myocardial infarction (MI) of these 3 techniques has not been studied
      yet. METHODS: Valsalva maneuver with calculation of Valsalva ratio (VR) and deep
      breath test with calculation of difference between average maximal and minimal HR
      during first minute of test (HR difference - HRD) were performed in 188 patients
      on days 4-11 of MI (68.1% men, age 34-75 years, 93.6% on beta-blockers, without
      heart failure NYHA IV on the day of tests). Time and frequency domain HRV
      measures were assessed during 15 min at bed rest and at Holter monitoring for
      median 24 h on the same day as reflex tests. RESULTS: During follow up for 2.1+/
      0.8 years there were 9 sudden and 13 non-sudden cardiac deaths. ROC analysis was
      used to determine cut-off values of VR, HRD and HRV measures for dichotomization
      of patients into those with low- and high-risk of SD and these values were used
      in logistic regression analysis. The following parameters were univariate
      predictors of SD: obtained at reflex tests - VR <1.13 (OR 7.8, 95% CI 1.6-39.0;
      p=0.012), HRD <3.36 (OR 4.3, 95% CI 1.1-16.9; p=0.034); HRV parameters from 15
      min ECG recordings - total frequency power <739 ms(2), VLF power <294 ms(2), LF
      power <197 ms(2) and LF/HF <1.5; HRV parameters from long term ECG recording - LF
      power <491 ms(2), LF/HF <1.4. At multivariate analysis only LF power for 15 min
      <197 ms(2) among HRV parameters remained independent predictor of SD (OR 24.2,
      95% CI 2.4-245.5; p=0.007). Other predictors were clinical - VF during acute
      phase of MI (OR 94.7, 95% CI 4.2-2115.2; p=0.004) and history of MI (OR 8.4, 95%
      CI 1.4-48.5; p=0.017). CONCLUSION: In this population of patients without severe
      heart failure low LF power on 15 min resting ECG recordings on days 4-11 of MI
      was more powerful predictor of sudden cardiac death during subsequent 2 years
      than other HRV parameters including heart rate response to Valsalva maneuver and
      deep breath test.

PMID- 15477774
TI  - [The Use of Clopidogrel in Conjunction With Thrombolytic Therapy in PatientsWith
      ST-Elevation Acute Myocardial Infarction.].
AB  - Clopidogrel (300 mg before initiation of thrombolysis and 75 mg/day thereafter)
      was given to 46 of 131 patients with streptokinase treated ST-elevation acute
      myocardial infarction. Mortality and efficacy of thrombolysis were similar in 2
      groups, however deaths of acute heart failure were distributed unevenly (0 in
      clopidogrel group and 8 or 9.4% among other patients, p <0.03). Clopidogrel
      treated compared with other patients had significantly higher left ventricular
      ejection fraction on days 1-2 of disease (52.5+/-2.2 and 45.9+/-2.0%,
      respectively, p<0.03). Number of bleedings did not differ significantly between 2
      groups. Thus patients addition of clopidogrel to aspirin and thrombolysis with
      streptokinase was associated with better myocardial contractile function and
      lower mortality due to acute heart failure.

PMID- 15477775
TI  - [Organ-protecting ability of low-dose combination therapy of arterial
      hypertension on patients with diabetes mellitus type 2.].

PMID- 15477776
TI  - [Effect of carvedilol on blood levels of cytokines and symptoms of heart failure
      in patients with postinfarction cardiac dysfunction.].
AB  - Effect of 6 months treatment with carvedilol (25 mg/day) on blood levels of
      cytokines (interleukins 1alpha, 2, 6, 8, tumor necrosis factor alpha) and
      clinical symptoms of heart failure was studied in patients with cardiac
      dysfunction after myocardial infarction. Patients with NYHA class II heart
      failure, ejection fraction 50% and moderately lowered tolerance to physical
      exercise (n=21) initially had enhanced cytokine expression: blood content of
      interleukin (IL) 2 was 2.8 times, tumor necrosis factor (TNFalpha) 78%, IL-1alpha
      60% above normal level. Therapy with carvedilol in this group was associated with
      decreases of Il-2 (-23.8%), TNFalpha (-16.7%), IL-1alpha (-12.5%) (p<0.05-0.01).
      This was accompanied by alleviation of clinical symptoms and improved exercise
      tolerance. Patients with NYHA class III heart failure (n=16) with low left
      ventricular ejection fraction (30+/-2.7%) and low exercise tolerance had high
      levels of all studied cytokines. Levels of IL-2, TNFalpha and IL-1alpha were most
      elevated (3.1, 2.8 and 2 times higher than normal values, respectively). Therapy
      with carvedilol was associated with improvement of clinical symptoms and exercise
      tolerance (+35%, p<0.05)), increase of ejection fraction (+15%, p<0.05), decrease
      of left ventricular end systolic volume (-17.5%, p<0.05), and lowering of blood
      levels of TNFalpha (-31%), IL-2 (-17.4%), IL-1alpha (-15.6%). However cytokine
      levels remained substantially elevated compared with normal values. Carvedilol
      was well tolerated, and did not cause negative metabolic effects or other
      complications.

PMID- 15477777
TI  - [Low density lipoprotein receptor gene mutations in patients with clinical
      diagnosis of familial hypercholesterolemia.].
AB  - Low density lipoprotein receptor (LDLR) gene mutations cause familial
      hypercholesterolemia which is associated with elevated risk of ischemic heart
      disease. AIM: To define LDLR gene mutations in unrelated patients with
      heterozygous familial hypercholesterolemia in Russia. METHODS: PCR- single-strand
      conformation polymorphism analysis, automated DNA sequencing, and test for the
      presence of the apolipoprotein (apo) B-3500 mutation known to induce hereditary
      defect in apo-B-100. RESULTS: We found 6 novel mutations of LDLR gene designated
      E8X, 230insG, 671_679dupGACAAATCT, W422R, D461Y, and V698L. We also identified
      three missense mutations - C139G, E207K and R395W, which were previously
      described in FH patients from western populations. None of the studied persons
      had apo-B-3500 mutation. CONCLUSION: These findings broaden knowledge on
      mutations responsible for development of familial hypercholesterolemia and
      confirm molecular heterogeneity of this disease in Russia.

PMID- 15477778
TI  - [Changes of cardiovascular system during long existing syphilitic infection.].

PMID- 15477779
TI  - [Hormone replacement therapy and prevention of cardiovascular diseases.].

PMID- 15477780
TI  - [Stroke and Other Thromboembolic Complications of Atrial Fibrillation. Part III.
      Prevention With Other Antithrombotic Agents.].
AB  - In part IV of a series of papers on epidemiology and drug prevention of stroke
      and other thromboembolic complications of atrial fibrillation the authors present
      data on clinical pharmacology of low molecular weight heparins, ximelagatran,
      indobufen, triflusal, dipyridamole, ticlopidine, and clopidogrel. Efficacy of
      direct thrombin inhibitor ximelagatran was found in randomized trials to be
      similar to efficacy of warfarin however the use of ximelagatran required no
      laboratory control of coagulation parameters. Preventive efficacy of indobufen,
      triflusal, dipyridamole, ticlopidine, and clopidogrel was assessed in trials on
      patients with cardiovascular diseases substantial number of whom had atrial
      fibrillation. Data of retrospective analysis of these trials are scrutinized in
      this review.

PMID- 15477781
TI  - [Potential and perspectives of the use of portable ultrasound diagnostic systems
      in cardiology.].

PMID- 15477782
TI  - [Hypertension in postmenopausal women: medical and social significance and
      results of therapy with moexipril.].

PMID- 15477783
TI  - [Simple cardiovascular reflex tests in prediction of sudden death after
      myocardial infarction: which method to prefer?].
AB  - BACKGROUND: Some evidence exists that heart rate response to simple provocative
      maneuvers may predict sudden cardiac death (SD) after myocardial infarction (MI).
      However optimal test has not been not established yet. Aim of this study was to
      compare prognostic value of different noninvasive reflex tests after MI. METHODS:
      Four reflex tests were consecutively performed in 188 patients on days 4-11 of MI
      (68% men, age 34-75 years, 93.6% on beta-blockers, without heart failure NYHA IV
      on the day of tests). Time- and frequency domain heart rate variability measures
      were obtained during 5 min at active standing and at bed rest with controlled
      breathing 6 and 15 per minute. In addition difference between average maximal and
      minimal heart rate at first minute of breathing 6 per minute (HRD) and Valsalva
      ratio (VR) were calculated. ROC analysis was used to determine cut-off values of
      studied measures for dichotomization of patients into those with low- and high
      risk of SD and these values were used in logistic regression analysis. RESULTS:
      During follow up for 2.1+/-0.8 years there were 9 SD. Univariate predictors of SD
      were follows: HRD <3.36; VR <1.13; pNN 50 <2.5, total spectral power <1021 ms(2),
      LF power <229 ms(2) and HF power <65 ms(2) at active standing; pNN 50 <2.3, LF
      power <129 ms(2) and HF power <111 ms(2) during controlled breathing 15 per
      minute. HF power <65 ms(2) during active standing (OR 28.8, 95% CI 4.1-104.2;
      p=0.0001, positive predictive value 29.4%) and VR <1.13 (OR 6.0, 95% CI 1.02
      34.3; p=0.04, positive predictive value 11.5%) were independent predictors of SD.
      For combination of these parameters OR increased to 34.9 (95% CI 6.7-181.6;
      p<0.001), positive predictive value to 50%. CONCLUSION: Among simple noninvasive
      reflex tests in this small group of patients with routine beta-blockers use and
      without severe heart failure active standing with calculation of HF power seems
      preferable method for prediction of SD after MI. Its predictive value may be
      enhanced by combination with Valsalva ratio.

PMID- 15477785
TI  - [Prognostication of the course of stable ischemic heart disease by exercise
      stress echocardiography].
AB  - We analyzed data from 549 patients (450 with high and 99 -- low pretest
      probability of ischemic events). Duration of observation was 12-42 (mean 20.1+/
      11.6) months. End points were death, nonfatal myocardial infarction, and
      revascularization. Cox proportional hazards model was used for assessment of
      relationship between clinical-instrumental data and events. One year risk of
      cardiac death and nonfatal myocardial infarction was 3 and 15%, event free
      survival -- 95 and 66% for patients with negative and positive result of stress
      echocardiography, respectively. Besides local contractility disturbances total
      test duration less than 6 min was significantly related to prognosis of main
      events while left ventricular hypertrophy, amount of METs, development of angina
      during stress test, and hypertensive disease were predictors of combined end
      point (death, nonfatal myocardial infarction, or revascularization). Thus results
      of exercise stress echocardiography had high prognostic power in patients with
      ischemic heart disease.

PMID- 15477784
TI  - [Correction of baroreflex sensitivity impairment and efficacy of prevention of
      sudden arrhythmic death in patients with postinfarction left ventricular
      dysfunction].
AB  - Baroreflex sensitivity was assessed in 287 patients with history of myocardial
      infarction and left ventricular ejection fraction < or =40% by phenylephrine test
      and was found to be depressed (4.44+/-0.38 ms/mm Hg). Repeat study in 3, 6 and 12
      months revealed substantial improvement of baroreflex sensitivity in patients
      treated with perindopril especially when it was combined with amiodarone,
      metoprolol, bisoprolol and carvedilol but not with atenolol. Combined therapy
      with amiodarone and carvedilol provided greatest reduction of sudden arrhythmic
      and total mortality. Superiority of combination of amiodarone with lipophilic
      beta-adrenoblocker over monotherapy had been anticipate but was not confirmed in
      any of large prospective studies.

PMID- 15477786
TI  - [Trends of main risk factors of coronary heart disease in Kaunas population
      during 20 years (the data of the MONICA study)].
AB  - MONICA (Multinational MONItoring trends and determinants of CArdiovascular
      diseases) study was carried out in Kaunas in 1983-2002 in four random samples of
      population aged 35-64 years (overall 3292 men and 3548 women - response rate
      65.1%). Over the 20-year period, mean levels of systolic blood pressure (BP) (in
      men and women), diastolic BP (in women), body mass index (in men and women)
      decreased while mean levels of total serum cholesterol increased (in men and
      women). In the final survey as compared with initial survey arterial hypertension
      (AH) (BP > 140/90 mm Hg) became less prevalent in women (39.4% and 51.3%,
      p<0.001) and mild hypertension - less prevalent in men (25.9% and 33%, p<0,001).
      Over the study period, prevalence of mild hypercholesterolemia (total cholesterol
      5.0-6.49 mmol/l) decreased and prevalence of severe hypercholesterolemia (total
      cholesterol =7.8 mmol/l) increased both in men and women. The prevalence of
      excessive weight increased in men and the prevalence of obesity increased in
      women. No statistically significant changes were detected in the prevalence of
      smoking in men during the study period while in women the prevalence of regular
      smoking increased (from 4.1% to 11.3%, p 0,001). The observed levels and trends
      of main risk factors of coronary heart disease require intensification of
      implementation of primary prevention measures in the studied population.

PMID- 15477787
TI  - [Amiodarone-associated thyroid dysfunction: prevalence and possibilities of
      correction].
AB  - During 1 year of amiodarone intake development of amiodarone-associated thyroid
      dysfunction was observed in 25% of patients (hypothyroidism and thyrotoxicosis in
      19.2 and 5.8%, respectively). Development of hypothyroidism was not accompanied
      with loss of antiarrhythmic efficacy of amiodarone and therapy with L-thyroxin
      was conducted at the background of continued amiodarone intake. In all patients
      with clinical and in less than one half (47.6%) of patients with subclinical
      forms of hypothyroidism replacement therapy with L-thyroxin was carried out.
      Development of amiodarone-associated thyrotoxicosis was accompanied with loss of
      antiarrhythmic efficacy of amiodarone in all cases. In all patients with
      thyrotoxicosis which developed during amiodarone intake thyrostatic therapy with
      mercasolil was carried out and in case of its inefficacy prednisolone was added.
      In 87.5% of patients with thyrotoxicosis correction of the thyroid status was
      conducted under conditions of continued amiodarone intake as this drug had been
      prescribed because of life saving indications. Achievement of euthyroid state was
      followed by restoration of antiarrhythmic efficacy of amiodarone. Amiodarone was
      discontinued just in 1 patient with ventricular extrasystole as correction of
      thyroid status and restoration of euthyroidosis enabled effective use of other
      antiarrhythmic drugs.

PMID- 15477788
TI  - [Assessment of efficacy of combined therapy with antihypertensive agents and
      biguanides in patients with metabolic syndrome].
AB  - To compare effects of antihypertensive and combined therapy on 24-hour blood
      pressure, biochemical parameters and chronic hyperinsulinemia in patients with
      metabolic syndrome. 54 patients with metabolic syndrome were observed during 8
      weeks. 28 patients (group A) were treated with antihypertensive agents (calcium
      antagonists, and when required -- ACE inhibitors and diuretics). 26 patients
      (group B) received the same therapy plus metformin. There were no significant
      changes in parameters of lipid and carbohydrate metabolism in group A. In group B
      we found significant decrease in C-peptide (p<0.05) and triglyceride (p<0.1)
      levels and increase in high density lipoprotein cholesterol levels (p<0.01). The
      combined antihypertensive and metformin therapy has a significant effect on
      carbohydrate and lipid metabolism.

PMID- 15477789
TI  - [Clinical value of degree of blood pressure lowering during use of effective
      doses of antianginal drugs].
AB  - Paired exercise tests with single doses of verapamil, nifedipine, propranolol,
      buccal nitroglycerin (trinitrolong), sustained release oral nitroglycerin, and
      placebo were performed in 101 patients with stable class II-III angina and the
      drug causing longest exercise duration was selected for long term therapy.
      Efficacy of a selected drug was compared with magnitude of its hypotensive
      effect. The latter was calculated as difference between blood pressure (BP)
      before and 2 hours after drug administration. Lower quintile of distribution of
      BP differences (systolic BP difference >20 mm Hg and/or diastolic BP difference
      >15 mm Hg) was considered as excessive hypotensive effect of a study drug (EHESD)
      single dose. Exercise duration before ST-segment depression was significantly
      shorter (p<0.05) in cases with EHESD compared with those without EHESD. After 1
      month of therapy total daily number of episodes of myocardial ischemia decreased
      by 3.2+/-3.0 and 1.8+/-1.2 in patients without and with EHESD, respectively
      (p<0.02). At the same time number of episodes of painless ischemia increased more
      than 2 times in patients with EHESD (p<0.01). Registration of EHESD at initial
      stages of treatment with short acting antianginal drugs appears to be a reliable
      marker of increased frequency of painless episodes of myocardial ischemia and low
      efficacy of regular use of these drugs.

PMID- 15477790
TI  - [Clinical efficacy of citalopram in patients with hypertension and concomitant
      depression].
AB  - Patients (n=28) with mild to moderate hypertension and depression were given
      enalapril (20 mg/day). If target blood pressure was not achieved in 10 days
      hydrochlorothiazide (12.5 mg/day) was added. These patients were randomized into
      2 groups in one of which antihypertensive therapy was supplemented with
      citalopram (20 mg/day) for 6 weeks. Psychological status was assessed by Beck
      Depression Inventory (BDI) and Spielberger State-Trait Anxiety Inventory (STAI).
      Total BDI score in citalopram group decreased 51% (-12.2+/-1.5; p<0.001).
      Complete reduction of symptoms of depression (BDI score <19) occurred in 86% of
      patients. There was no significant lowering of BDI score in control group. STAI
      score among citalopram treated patients with concomitant anxiety (STAI score >50)
      decreased from initial 62.9+/-2.1 to 46.3+/-3.1 by week 6 (p<0.001). Only minor
      changes of STAI score took place in control group. According to data of 24-hour
      monitoring lowering of systolic blood pressure time indexes was somewhat more
      pronounced in citalopram group than in control group (24 hour -49.8 and -34.4%,
      diurnal -56.6 and -42%, nocturnal -37.9 and -23%, respectively).

PMID- 15477791
TI  - [Assessment of effects of angiotensin converting enzyme inhibitor perindopril on
      function of endothelium of arterial vessels in patients with ischemic heart
      disease and hypertension].

PMID- 15477792
TI  - [Effects of lisinopril on platelet aggregation in patients with arterial
      hypertension with metabolic syndrome].

PMID- 15477793
TI  - [Effects of long acting fluvastatin on parameters of lipid metabolism in patients
      with type 2 diabetes and combined hyperlipidemia].

PMID- 15477794
TI  - [Increased platelet aggregation induced activity by anti-glycoprotein IIb/IIIa
      antibody in patients with acute coronary syndrome].
AB  - Interaction of glycoprotein (GP) IIb/IIIa with fibrinogen is the final and key
      reaction in platelet aggregation. In order to evaluate GP IIb-IIIa functional
      activity in patients with acute coronary syndrome (ACS) we measured platelet
      aggregation induced by monoclonal antibody CRC54 which is directed against GP
      IIb/IIIa and is able to stimulate its binding with fibrinogen and subsequent
      aggregation. Patients with ACS were divided into 3 groups: (1) with Q-wave
      myocardial infarction (MI), (2) with non Q-wave MI and with unstable angina.
      Patients with stable angina (SA) and healthy donors formed 2 comparison groups.
      The level and rate of CRC54-induced aggregation measured both in the absence and
      in the presence of prostaglandin E(1) (PGE(1)), the inhibitor of platelet
      activation, in all groups of patients with ACS were > or =1.5 times higher than
      in SA patients and healthy donors. Observed differences in the parameters of
      CRC54-induced aggregation at least in the presence of PGE(1) could be caused only
      by increased GP IIb/IIIa fibrinogen binding ability in ACS patients, but not by
      differences in the level of platelet activation. In all groups of patients with
      ACS, but not in SA patients and healthy donors, strong correlation (r=-0.5-0.7)
      was observed between increased parameters of ADP-induced aggregation and
      aggregation stimulated by CRC54 in the presence of PGE(1). The data obtained
      indicated that increased of platelet aggregating capacity in ACS might be caused
      by changes of GP IIb/IIIa functional characteristics and not by enhancement of
      platelet sensitivity towards physiological agonists including ADP.

PMID- 15477795
TI  - [Selective microproteinuria as a marker of incipient renal impairment in patients
      with hypertension].
AB  - Incidence of chronic renal failure has a worldwide tendency to growth.
      Hypertension occupies an important place among causes of this upward trend. That
      is why in patients with hypertension and incipient changes of the kidneys it
      seems most appropriate to use antihypertensive drugs with renoprotective
      properties. Early treatment with these drugs enables most effective lowering of
      risk of renal failure development and thus has a potential to prolong life of a
      patient. Selective microproteinuria is considered to be a marker of incipient
      renal impairement. Among groups of antihypertensive agents angiotensin converting
      enzyme inhibitors, angiotensin receptor blockers, calcium antagonists, beta
      blockers, and diuretics have proven renoprotective properties.

PMID- 15477797
TI  - [Risk of myocardial infarction is determined by nine well known factors in a
      similar way all over the world].

PMID- 15477798
TI  - [Final confirmation of inefficiency of antibiotics in secondary prevention of
      coronary heart disease. Results of PROVE IT (gatifloxacin trial) and ACES].

PMID- 15477799
TI  - [Statins: therapeutic cascade of their effects].
AB  - Concept of sequence and time of appearance of various effects of statins is
      presented. Apart from hypolipidemic action due to inhibition of HMG CoA reductase
      activity statins exert multiple pleiotropic effects. Combination of these effects
      makes statins a unique instrument for solution of global tasks of prevention and
      treatment of atherosclerosis and its consequences (ischemic heart disease etc.).
      Manifestations of various pleiotropic effects of statins appear after different
      time intervals and in most cases are not related to suppression of cholesterol
      synthesis in the body. First 3-4 months (first level of the statin cascade) are
      characterized mainly by activity of pleiotropic properties aimed at restoration
      of endothelial function. These properties are responsible for enhanced eNOS
      expression, antiischemic, antithrombotic and antiatherogenic effects. During same
      period of time stabilization of unstable atheromas takes place. Manifestations of
      second level of the cascade of statin action appear after 2 years of treatment.
      They are represented by retardation of progression and even partial regression of
      atheromatosis of coronary and peripheral arteries. Third level is signified by
      achievement of strategic aims of therapy with statins (in 4-5 years) -- lowering
      of total and cardiac mortality, reduction of number of cardiac complications.
      Forth level of the cascade is represented by beneficial influences on
      nonatherogenic cardiological phenomena and comprise hypotensive, antiarrhythmic
      and cardiotonic effects. And finally some other important properties of statins
      constitute the fifth level of the therapeutic cascade. These properties are
      responsible for effects directed at noncardiac pathology (prevention of diabetes,
      dementia, including dementia associated with Alzheimer's disease, fractures).
      Immunodepression, ability to reduce saturation of bile with cholesterol belong to
      this group of effects.

PMID- 15477800
TI  - [Novel approaches to the management of patients with stable ischemic heart
      disease].

PMID- 15477801
TI  - [Hyperhomocysteinemia: from theory and practice in the treatment of
      thrombophilias].

PMID- 15477802
TI  - [Development of transmural myocardial infarction in young persons with intact
      coronary arteries during methadone use for the treatment of heroine addiction].
AB  - Linkage between acute coronary syndrome and narcotic drug (cocaine) intake was
      first described by D. Colleman in 1982. However risk of development of acute
      myocardial infarction during replacement therapy after opioid withdrawal has not
      been elucidated. The paper contains description of two cases of development of
      myocardial infarction in young persons with intact coronary arteries who received
      synthetic opioid methadone for facilitation of heroine discontinuation. These
      clinical cases should draw attention of physicians to side effects of the use of
      methadone for the treatment of heroine addiction.

PMID- 15477803
TI  - [Surgical treatment of patients with aortic aneurysm and ischemic heart disease].
AB  - Experience in the treatment of 153 patients with aortic aneurysms and ischemic
      heart disease was analyzed. Twenty-five patients with ischemic heart disease
      underwent reconstructive surgeries for thoracic and thoracoabdominal aneurysms of
      the aorta. Reconstructive surgeries on the aorta without ones on coronary
      arteries were performed in 3 of them. In the rest of the 22 patients both
      myocardium revascularization and aortic reconstruction were performed.
      Combination of abdominal aorta aneurysms with ischemic heart disease was seen in
      128 patients, all of them were operated. Reconstruction of the abdominal aorta
      without coronary surgery was performed in 109 patients. Myocardium
      revascularization as the first stage of surgery was performed in 8 patients.
      Eleven patients underwent simultaneous surgeries on the coronary arteries and
      abdominal aorta. Technical features of different variants of surgeries were
      developed and described in detail. It is concluded that simultaneous surgeries on
      the aorta and coronary arteries permit to achieve good results in patients with
      aortic aneurysms and ischemic heart disease. Simultaneous grafting of thoracic
      and thoracoabdominal aorta with coronary arteries bypass leads to positive
      results in 90.9% cases.

PMID- 15477804
TI  - [Surgical treatment of patients with arrhosive bleedings undergone reconstructive
      surgeries on the aorta and lower limbs arteries].
AB  - Results of surgical treatment of 25 patients with arrhosive bleedings were
      analyzed. All of them had functioning shunts and severe infectious complications
      of the wounds in the region of Scarp's triangle. Infected wounds existed from 15
      days to 18 months. Bleeding from the wound of Scarp's triangle was seen in 96%
      cases (24). Insufficiency of distal anastomosis due to arrhosia was in 15
      patients (60%). Arrhosive bleeding from anastomosis of the synthetic graft with
      aorta or common iliac arteries was in 8 (32%) cases, insufficiency of distal
      anastomosis of femoral-tibial bypass was seen in 2 (8%) patients. Various
      extrafocal surgeries are method of choice in the treatment of arrhosive
      bleedings. These surgeries may be performed simultaneously (at first bypass, then
      removing of graft) or during 2-3 stages in lengthy purulent-inflammatory process.

PMID- 15477805
TI  - [Revascularizing osteotrepanation in combined surgical treatment of chronic lower
      limb ischemia].
AB  - Short and long-term results of revascularizing osteotrepanations by Zusmanovich's
      method performed in 80 patients with lower limb critical ischemia were analyzed.
      The operation is effective in distal and diffuse forms of atherosclerosis and
      inflammatory diseases if it is impossible to perform reconstruction. Isolated
      revascularizing osteotrepanation is indicated for patients with recurrence of
      critical ischemia who earlier have undergone conventional surgical procedures.
      Duplex sonography is the main method for diagnosis and determination of
      indications for surgery which provides an objective criterion of the treatment
      failure - the index of tibial arteries resistance.

PMID- 15477806
TI  - [Surgeries on major vessels in removal of different tumors].
AB  - Experience in diagnosis and surgical treatment of 49 patients with tumors of
      different localization close to their major with main vessels is analyzed. Two
      variants of tumor - vessel interrelation were seen, patients with iatrogenic
      vascular lesions were included into a separate group. In 9 patients (group 1)
      only extravasal compression by the tumor was seen. Most of these tumors were
      benign. In 15 patients (group 2) reconstructive vascular surgeries were performed
      because of close interrelation with the tumor or tumor spread into the vessel.
      Most of these tumors were malignant. Iatrogenic lesions of arteries during
      surgeries were in 25 patients (group 3). It is demonstrated that duplex
      sonography permits to diagnose affection of vessels by tumors without invasive
      procedures. All the patients underwent vascular reconstruction simultaneously
      with tumor removing. Sceletization of vessels with their decompression was the
      surgery of choice in benign tumors. In malignant tumors it is recommended to
      remove the tumor with affected segment of vessel and repair of blood flow.
      Ligation of vessel may be justified in some cases.

PMID- 15477807
TI  - [Migration of the fragment of the subclavian catheter: diagnosis and surgical
      treatment].
AB  - Results of examination and surgical treatment of 68 patients after migration of
      foreign body (fragment of catheter) into venous bed were analyzed. Ultrasonic
      examination including transesophageal echocardiography was the main method of
      diagnosis. Various surgical approaches were used depending on localization of the
      foreign body. Policy of surgical treatment was developed. A case is reported.

PMID- 15477808
TI  - [Correction of enteral insufficiency syndrome in general peritonitis].
AB  - Efficacy of enteral ozone lavage in combined treatment of patients with general
      peritonitis is analyzed. It is demonstrated that intestinal lavage with ozone
      enriched physiological salt solution through nasointestinal probe in
      postoperative period eliminates effectively bacterial contamination of the
      intestine, decreases toxicity of enteral contents and leads to significant
      improvement of functional characteristics of the small intestine and results of
      treatment.

PMID- 15477809
TI  - [Active policy in treatment of bleeding ulcer: update].
AB  - Results of treatment of 2256 patients with ulcerous gastroduodenal bleeding are
      analyzed. From 1993 to 2000 continued bleeding and high risk of it were
      indications for urgent surgery. Postoperative lethality after surgeries in active
      bleeding was 9.3%. Experience with endoscopic hemostasis limits indications for
      urgent surgeries. Results of treatment during two period were compared: when
      active surgical policy was used (486 patients) and when endoscopic hemostasis was
      often performed (503 patients). Surgical activity during the latter period
      reduced significantly (from 52.3 to 31.5%). Postoperative lethality decreased
      from 9.45 to 6.25%, total lethality -- from 4.94 to 2.36%.

PMID- 15477810
TI  - [Gastrectomy with end-loop jejunogastroplasty in stomach cancer].
AB  - Experience with surgical treatment of 147 patients after gastrectomy with
      jejunogastroplasty and creation of end-loop esophageal-intestinal anastomosis is
      analyzed. Original methods of jejunogastroplasty are based on end-loop
      construction of esophageal-intestinal anastomosis simulating anatomic-functional
      analog of lost cardia and pylorus and replacing reservoir function of the
      stomach. One year and later after surgery 83 patients with end-loop esophageal
      intestinal anastomosis and 73 patients with anastomosis were examined. It is
      demonstrated that jejunogastroplasty with end-loop anastomosis is characterized
      by low frequency (6%) and degree of reflux-esophagitis. Passage of food through
      duodenum in end - loop jejunogastroplasty decreases frequency and degree of
      demping-syndrome. Active isolating function of end-loop anastomosis was
      demonstrated with x-ray and manometric methods. Primary jejunogastroplasty with
      end-loop anastomosis leads to reduction of frequency and severity of
      postoperative pathological syndromes and permits to improve quality life of
      operated patients.

PMID- 15477811
TI  - [Papillovirsungocystoduodenoplasty in the treatment of cysts of the pancreatic
      head].
AB  - Experience in the treatment of cystic lesions of the pancreatic head is analyzed.
      The method of internal drainage of the pancreatic head cyst with transduodenal
      approach is described. This methods includes three stages:
      papillosphincteroplasty, deep virsungotomy with virsungoplasty and
      cystovirsungoplasty through ducts. The method is named
      papillovirsungocystoduodenoplasty (PVCDP). Results of 6 successful PVCDP are
      presented. There were neither recurrence of the cyst nor lethal outcomes.

PMID- 15477812
TI  - [Anaerobic non-clostridial infection in acute appendicitis].
AB  - Etiological factors promoting anaerobic non-clostridial infection (ANI) after
      appendectomy are analyzed for the last 10 years (1993-2002). Acute appendicitis
      was the indication for appendectomies in 2846 patients. In 55 (1.9%) patients ANI
      was detected 2-7 days after surgery. Later than 24 hours since beginning of the
      disease 40 (72.7%) patients were hospitalized. Diagnosis of ANI was based on
      typical clinical symptoms confirmed with bacteriological and morphological
      examinations. Treatment of ANI was complex: early radical surgery, massive
      antibiotic therapy, hyperbaric oxygenation, intensive care. 10-14 days after the
      last necrectomy (wound area from 139 to 1812 cm(2)) repair dermal-plastic
      surgeries were performed in 48 (87.3%) patients with good functional and cosmetic
      results. Two (3.6%) patients with ANI died. Of six patients with general forms of
      ANI admitted from other hospitals 3 patients died. Sepsis was the main cause of
      death. Late surgeries in general forms of ANI lead to worse results.

PMID- 15477813
TI  - [Appliance of "LigaSure" generator in hemorrhoidectomy].
AB  - Results of hemorrhoidectomy in 185 patients were analyzed. In 82 patients of the
      study group surgery was performed with "LigaSure" generator. Control group
      consisted of 103 patients who underwent surgery by Milligan-Morgan method.
      Appliance of "LigaSure" generator to reduced time of surgery by 3.5 times (from
      48+/-10.3 min to 13+/-3.7 min), pain syndrome -- 2.2 times, and dysuric disorders
      -- 2.4 times.

PMID- 15477814
TI  - [Hernioplasty with synthetic net in ventral hernias].
AB  - Results of abdominal hernioplasty with synthetic materials in 206 patients with
      various abdominal hernias were analyzed. Polypropylene nets ("Ethicon" and
      "Lintex") proved effective and high-quality. Postoperative complications
      (subcutaneous seromas in most cases) were analyzed. There were no lethal
      outcomes, recurrences. It is concluded that up-to-date synthetic materials
      improve results of surgical treatment of abdominal hernias.

PMID- 15477815
TI  - [Transosseous osteosynthesis with Gorodnichenko's devices in the treatment of
      polytrauma].
AB  - From 1997 to 2003 eighty-three patients with poly- and multiple fractures
      underwent transosseous osteosynthesis with rod and pin-rod Gorodnichenko's
      devices, without drilling of bone marrow canal. Primary osteosynthesis was
      performed during 48 hours after trauma. The new pin apparatus of external
      fixation were the best method of osteosynthesis of poly- and multiple fractures
      in patients with polytrauma. This policy permitted to achieve good and
      satisfactory results in 94.3% patients with polytrauma.

PMID- 15477816
TI  - [Application hemostatic drug in capillary-parenchymatous bleeding].
AB  - Specific activity of a new hemostatic drug thrombocol was studied in experiments.
      Laboratory rabbits were used for management of experimental capillary
      parenchymatous hemorrhage. The action of thrombocol was compared with hemostatic
      effect of other drugs: carbocol, combutek-2, super-4 (USA), collastipt (Germany),
      collagen sponge (Germany). It was found that thrombocol was highly hygroscopic,
      showed good adhesion to wounded surface, high plasticity and better hemostatic
      effect compared with other collagen-containing drugs.

PMID- 15477817
TI  - [Subtotal distal resection of the stomach in cancer: indications and immediate
      results].
AB  - Results of 193 subtotal distal resections of the stomach due to cancer are
      analyzed. Age of the patients ranged from 25 to 87 years (mean age 57+/-11
      years). Reconstruction by Bilrot-I technique was performed most often (67%
      cases). When Bilrot-II technique was used, classical Gofmeister-Finsterer variant
      and method on "ultrashort" loop with transverse anastomosis were performed.
      Extended lymphadenectomy (LAE) was performed in the majority of patients -- 131
      (68%) including in D2 volume -- 111 (58%), in D3 - 20 (10%). Combined surgeries
      were carried out in 23 (12%) patients. The following intraoperative complications
      were seen: trauma of the spleen (2 patients, splenectomy was performed) and an
      injury of the portal vein during removing of the lymph nodes of 8b group (1
      patient, wound of the vein was sutured). Postoperative complications were seen in
      37 (19,2%) patients. There was one case of insufficiency of gastric anastomosis
      due to surgical mistake. Two patients died (1 after stomach resection with LAE in
      D1 and 1 -- after one in D3), lethality was 1%. Mesenterial thrombosis and
      perforation of acute ulcer of the gastric stump were the causes of death. It is
      demonstrated that LAE in D2 scope doesn't influence immediate results of distal
      resection of the stomach in cancer. LAE in D3 scope compared with D2 is
      associated with increased number of complications.

PMID- 15477818
TI  - [Prophylaxis and treatment of complications after resection of the stomach with
      Roux anastomosis].
AB  - One hundred and seventy-eight subtotal distal resections of the stomach with
      creation of the valve in an outflowing part of the small intestine were analyzed.
      There was no postoperative lethality due to the method of surgery. One (0.6%)
      patient died on day 18 after surgery for acute cardiac insufficiency. General
      surgery complications were seen in 3 (1.7%) cases. In 2 (1.1%) patients Roux
      syndrome developed, it was treated conservatively on day 12 - 18. Repair of
      tonisity, peristalsis of the gastric stump and diverting intestinal loop was
      registered late after surgery. Mild forms of damping-syndrome were diagnosed in
      2.8% cases, superficial gastritis of the gastric stump -- in 33.3%, atrophic
      gastritis -- in 11.1%. The intestinal valve provided physiological evacuation and
      impeded reflux into the gastric stump.

PMID- 15477819
TI  - [Electrosurgical technology of the closed type in the treatment of ulcer
      disease].
AB  - Based on experiments (n=36), studies on cadavers (n=17) and clinical studies
      (n=462) advantages of developed electrosurgical method of creation of one-row
      gastroduodenal anastomosis of a closed type are shown. It heals better compared
      with two-row sutures. Good conditions of tissues trophicity lead to a decrease of
      alteration and improvement of reparative processes. Clinical studies demonstrated
      reliability of anastomosis. It provides minimal postoperative complications,
      including potentially fatal ones. It is easy for surgeon, doesn't require large
      mobilization of duodenal stump even in difficult cases.

PMID- 15477820
TI  - [Diagnosis and surgical treatment of gastric ulcers of proximal localization].
AB  - Over 15 years 208 patients with ulcers of the proximal part of the stomach (36
      cardial and 172 subcardial) underwent surgery that constitutes 17,5% of all
      gastric ulcers. Seventy-two patients had uncomplicated ulcers, complications were
      diagnosed in 135 including 34 (16,4%) cases of malignant transformation.
      Successful surgical treatment of a proximal part of the stomach is based on
      timely complex diagnosis. High rate of complications dictates that conservative
      treatment of these ulcers should be limited to 6 months - 1 year. Indications for
      surgery must be also regarded when up-to-date drug therapy is ineffective during
      2-3 months. Proximal and distal resection of the stomach are the main methods in
      surgical treatment of patients with benign ulcers of the cardia and subcardia. In
      malignant ulcer gastrectomy is recommended.

PMID- 15477821
TI  - [Postoperative intraabdominal bleedings].
AB  - Based on complex diagnosis and treatment of 58 patients with postoperative
      intraabdominal bleedings (PIB), clinical classification and adequate surgical
      policy are proposed. It is demonstrated that in PIB of degree II-III urgent
      relaparotomy is indicated. In PIB of degree I dynamic follow-up of drainages,
      hemodynamic and hematological indices are possible.

PMID- 15477822
TI  - [Programmed relaparotomy in generalized purulent peritonitis].
AB  - Efficacy of programmed relaparotomy in combined treatment of 51 patients with
      generalized peritonitis is analyzed. Based on evaluation of surgical data, basic
      clinical and laboratory markers of endotoxicosis algorithm of programmed
      relaparotomy has been developed. Comparative analysis of the results of treatment
      of 36 patients after 1-2 programmed relaparotomies (1.6+/-0.5 surgeries) and 15
      patients after repeated relaparotomies (3.4+/-0.3 surgeries) demonstrated that
      these methods were more effective before development of significant polyorganic
      disturbances. Nine (17.6%) patients died.

PMID- 15477823
TI  - [Treatment of intestinal insufficiency syndrome in patients with peritonitis].
AB  - Results of the treatment of 90 patients with generalized peritonitis and syndrome
      of intestinal insufficiency were analyzed. In the study group (45 patients)
      enteral administration of 1% pectin solution and glutamin solution (15-30 g/day)
      were included in combined therapy. Clinical and laboratory control, radiation
      monitoring and bacteriological studies carried out for evaluation of efficacy of
      therapy established. A decrease of endogenous intoxication and time of repair of
      functional activity of the gastrointestinal tract, immunomodulation,
      normalization of microbiocenosis of the small intestine. This therapy diminishes
      the number of complications and lethality.

PMID- 15477824
TI  - [Surgical treatment of patients with colostoma].
AB  - Results of treatment of postcolostomy patients are analyzed. In 74.7% cases
      colostoma was created due to tumor of the rectum or colon, in 6.5% -- due to
      diverticulosis, in 3.5% -- due to nonspecific ulcerative colitis, Krohn's and
      other diseases. Complications were diagnosed in 15.2% patients. Surgical
      treatment was carried out in 714 (43.6%) patients, 568 (79.5%) of them underwent
      reconstructive surgeries, 146 (20.4%) were operated for stoma complications. New
      methods of rectal stump preparation for surgery were used: method of
      differentiation of rectal stump and urether during surgeries, methods of delayed
      anastomosis. Laparoscopic mobilization of the colon during reconstructive
      surgeries led to a decrease of surgical trauma and number of complications.

PMID- 15477825
TI  - [Hemostatic disturbances after aorto-femoral and femoro-popliteal bypasses in
      patients with lower limbs obliterating atherosclerosis].
AB  - Forty-seven men aged from 38 to 74 years with lower limb obliterating
      atherosclerosis (III-IV degree, indication for surgery) were examined. Growth of
      lipoperoxides level, a decrease of antioxidant potential, activation of
      hemostasis were revealed. These phenomena intensified after bypass surgeries and
      persisted till discharge. Supplement of standard therapy with antioxidant
      selmevit limited degree of disturbances before and after surgery, accelerated
      normalization of hemostasis.

PMID- 15477826
TI  - [Laparoscopic surgeries in the treatment of hiatal hernias].
AB  - Immediate and long-term results of treatment of 132 patients with hiatal hernias
      are analyzed. Indications for surgery are determined. Complications during and
      after laparoscopic antireflux surgeries are analyzed.

PMID- 15477827
TI  - [Endoprosthesis of great joints of extremities in difficult anatomic conditions].
AB  - Experience in endoprosthesis of great joints in 408 patients in difficult
      clinical cases associated with defects and deformations of bones of
      posttraumatic, oncological, dysplastic and systemic character, and also in the
      cases of complications after primary endoprosthesis is analyzed. Special
      constructions of implants, instruments, surgical technique were used depending on
      anatomic and functional changes. Results of endoprosthesis of great joints were
      accessed as successful in 95% patients in maximal period of follow-up during 13
      years.

PMID- 15477828
TI  - [Combined trauma of the abdomen and pelvis].
AB  - Experience in treatment of 164 patients with combined trauma of abdomen and
      pelvis is analyzed. Mean age of the patients was 40.1+/-17 years, 94 patients
      were male, 70 -- female. ISS was 28.6+/-11 points. Lethality was 44.5%, during
      first day -- 61.6%. High lethality may be associated with mistakes in surgical
      and traumatological policy. Abdominal surgery was performed in 64 (39%) patients,
      only in 24 (14.6%) of them laparotomy was curative, the rest 40 (85.4%) patients
      underwent diagnostic laparotomy. It is demonstrated that diagnostic laparotomy
      has negative influence on prognosis of combined trauma of the abdomen and pelvis.
      Adequate traumatological policy has also great influence on lethality,
      particularly during the first day. Overall lethality of patients with rotary
      vertical instability of the pelvis was lower in the group with fixation of the
      pelvis than in conservatively treated patients (41.7 and 56.6%). Lethality during
      day 1 in patients with fixed pelvis was 0, without fixation of the pelvis -- 82%.
      It is concluded that verified indications for laparotomy and active
      traumatological policy improve treatment results in patients with combined trauma
      of abdomen and pelvis.

PMID- 15477829
TI  - [Prophylaxis of wound infection with immobilized antibacterial drugs].
AB  - New drug ambipor that is an immobilized antibacterial agent with local prolonged
      therapeutic activity was developed for prophylaxis of wound suppuration. In
      ambipor A drugs gentamicin, dioxidin, kephzol and riphampicin are immobilazed, in
      iodopor - iodine. Experimental studies on 455 white rats showed that ambipor
      prevents suppuration, abscess formation around ligatures, improve regeneration
      and fibrillogenesis. In clinical practice ambipor A and iodopor were used in 562
      patients. Rate of suppuration decreased from 11.7 to 2.3% compared with control
      group of patients.

PMID- 15477830
TI  - [Photodynamic therapy and exogenous nitric oxide in combined treatment of
      purulent wounds of the soft tissues].
AB  - Results of treatment of 160 patients with purulent wounds of the soft tissues
      treated with photodynamic therapy and exogenous nitric oxide were analyzed. High
      efficacy of this method is demonstrated: clinical course of the disease improves,
      period of wounds healing and hospitalization reduces. Photodynamic therapy in
      combination with exogenous nitric oxide results in rapid repair of
      microcirculation, stimulation of phagocytosis, accelerates cleaning of wounds,
      activates macrophagal reaction, fibroblast proliferation and epithelium
      regeneration that is in stimulation of reparation.

PMID- 15477831
TI  - [Surgery without donor's blood].
AB  - Complex program "Surgery without blood" was developed and introduced into a broad
      clinical practice. The main elements of this program are stimulation of
      erythropoesis, preparing in autoserum and autoblood before surgery with acute
      normovolemic hemodilution method, precise surgical technique, reinfusion of blood
      from wound and drainages, adequate anesthesia and correction of hemostasis
      system. This program permits one to minimize infusion of donor's blood components
      (DBC) in elective surgery (cardiosurgery, orthopedic surgery, neurosurgery,
      oncology, general surgery) and reduce significantly transfusion of DBC in urgent
      surgery. Rejection of DBC transfusion decreases number of postoperative
      complications and hospital stay, improves results of treatment and is cost
      effective.

PMID- 15477832
TI  - [The status of dog dental pulp after preparation for metalloceramic crowns using
      temporary fixative cement containing calcium hydroxide].
AB  - Morphologic investigation of the condition of the pulp of teeth in 15 dogs in the
      use of different kinds of temporary fixing cements after preparation for meta
      ceramic crowns. It was determined microscopically that the use of the temporary
      fixing cement Provicol considerably diminishes inflammatory changes in the pulp
      of the prepared teeth and it assists the much quicker restoration of its normal
      histophysiology (normalization of oxidation-reduction processes, cellular
      elements of the pulp and especially the layer of the odontoblasts, their
      participation in formation of the replacing dentin).

PMID- 15477833
TI  - [Candida albicans adhesion to plastics during correction of removable dentures].
AB  - Colonisation of denture soft lining materials by Candida albicans can result in
      clinical problems. The presence of Candida albicans on the upper fitting surface
      of the denture is a major causative factor in denture-associated chronic atrophic
      candidosis (denture stomatitis). The fitting surface of denture can act as a
      reservoir of Candida albicans. The goal of our experiment was to determine of
      candidal adherence to two soft lining materials -- Ufi gel C temporary and Ufi
      gel P permanent. Results of experiment show that adherence of Candida albicans to
      the Ufi gel C temporary was significantly move than for Ufi gel P permanent.

PMID- 15477834
TI  - [Effects of replacement hormone therapy on dental enamel mineralization and
      demineralization in women with surgical menopause].
AB  - Replacement hormone therapy received by women with surgical menopause did not
      completely normalize mineralization and demineralization processes in the surface
      layer of dental enamel. The concentrations of calcium and inorganic phosphorus in
      the saliva remained low and dental enamel remained highly vulnerable to acid
      damage.

PMID- 15477835
TI  - [Effects of immunomodulating therapy on immune status and the disease course in
      patients with relapsing herpetic stomatitis].
AB  - Clinical and immunological efficiency of leukinferone in combination with
      polyoxidonium (immunomodulator) was studied in patients with relapsing herpetic
      stomatitis (RHS). The levels of alpha- and gamma-IFN were decreased, levels of
      IgM, IgG, and IgE were increased, active oxygen forms were actively produced, and
      the count of CD8(+)-cells was increased in patients with RHS. Treatment with
      polyoxidonium and leukinferone led to an increase of the blood levels of alpha-
      and gamma-IFN, decrease of IgM, IgG, and IgE levels, normalization of
      phagocytosis, and decrease of CD8(+)-cell count. The treatment had a pronounced
      clinical effect in patients with RHS of any severity, which indicates the
      efficiency of these drugs in combined therapy of patients with RHS.

PMID- 15477836
TI  - [Improving the efficiency of combined therapy of patients with leukoplakia of the
      buccal mucosa using Phytomix-40 combined plant preparation].
AB  - Today leukoplakia of the buccal mucosa is regarded as a typical pre-tumorous
      condition, both in medicine in general and in dentistry, in particular.
      Leukoplakia is in fact resistant to conservative treatment, and therefore search
      for new approaches to therapy of this disease is a pressing problem. Phytomix-40
      (PM-40) is a mixture of natural extracts of 40 medicinal plants developed for
      practical oncology. PM was used in combined therapy of patients with leukoplakia
      with good results.

PMID- 15477837
TI  - [Diverticulum of the submandibular salivary gland ducts].
AB  - Examinations of 125 patients with sialolithiasis showed abnormality of the
      submandibular duct (diverticulum with a sialolith in it) in 3 (2.4%) patients.
      The authors suggest that diverticulum of the submandibular duct is in fact a
      variant of its ectasia and can be regarded as a diagnostic nosological entity.

PMID- 15477838
TI  - [Repair of mandibular defects using dosed distraction. Part II. Bound osteoplasty
      of the mandible by distraction osteogenesis].
AB  - Five variants of bound osteoplasty based on the distraction osteogenesis
      phenomenon were developed by the author for the treatment of patients with
      gunshot mandibular defects during the war in Afghanistan. Three of these variants
      are described in this paper; indications for their use and the technique of
      operation are presented. In fact, bound osteoplasty for gunshot wounds is primary
      early osteoplasty of the mandible -- the target of several generations of
      maxillofacial surgeons.

PMID- 15477839
TI  - [Treatment of patients with unilateral upper and lower macrognathia].
AB  - The problem of medical rehabilitation of patients with unilateral upper and lower
      macrognathia is discussed. A method of osteo-reconstructive intervention on the
      facial skull is described, which restores the proper relationships between the
      jaw bones with respect to the supraorbital plane, which serves as the reference
      when planning surgical treatment. A comprehensive approach to planning and
      realization of surgical treatment brings about good esthetic and functional
      results.

PMID- 15477840
TI  - [Two-cog (pi-shaped) dental implants and preclinical validation of their use].
AB  - Based on the results of statistical analyses, the authors validate the need in
      development of a new optimal design of implants for replacement of removed
      mandibular molars. Two-cog (P-shaped) dental implants are suggested, which have
      been patented. Study of their biomechanical characteristics by digital
      experiments using three-dimensional final element simulation demonstrated the
      efficiency of this design of implants, particularly for direct and early
      implantation and confirmed the adequacy and validity of the two-cogs implants.

PMID- 15477841
TI  - [A case with osteochondroma of the mandibular condyle].
AB  - A rare case with osteochondroma located near the condylar process of the mandible
      is described. Surgical treatment was carried out (removal of the formation
      through the periauricular approach). Orthopedic treatment was carried out during
      the postoperative period. The proportions of the facial skull, occlusion, and
      articulation were completely restored.

PMID- 15477842
TI  - [Relationship between incisor position and status of facial soft tissues].
AB  - Thirty patients with sagittal, vertical, and transverse abnormalities of
      occlusion combined with abnormal position of the frontal teeth and improper shape
      and size of dentition were examined. The position of maxillary canines was
      evaluated by the method suggested by L. Garner (1974) determining the
      relationship between the location of frontal teeth and position of soft facial
      tissues.

PMID- 15477843
TI  - [Inductive effect of bioactive substances on dental cell differentiation].
AB  - Qualitative and quantitative characteristics of neuromediator distribution in
      developing dental tissues are presented. Mechanisms of involvement of bioactive
      substances present in granular fluorescent cells and mast cells of the dental
      pulp in the regulation of tooth development are discussed. Relationship between
      the content of bioactive substances in the enamel organ and mesenchymal
      structures of a developing tooth and in bio-amine containing cells and nerve
      fibers is revealed, which can underlie one of the important mechanisms of their
      mutual inductive effects during the ontogenesis.

PMID- 15477859
TI  - The impact of preoperative breast biopsy on the risk of sentinel lymph node
      metastases: analysis of 2502 cases from the Austrian Sentinel Node Biopsy Study
      Group.
AB  - Preoperative breast biopsy might cause disaggregation of tumour cells and tumour
      cell spread. The purpose of this study was to investigate the impact of
      preoperative biopsy on the rate of metastases to the sentinel lymph node (SLN) of
      patients with primary breast cancer. We report the results of 2502 patients with
      primary breast cancer, who were operated, and a sentinel node biopsy was
      performed. The association of preoperative biopsy with the risk of SLN metastases
      was examined by regression analyses and tested for possible confounding well
      known factors for axillary node metastases. In all, 1890 patients were available
      for final analyses; 1048 (55.4%) patients had a preoperative diagnosis performed
      by fine-needle aspiration or core biopsy; 641 (33.9%) patients had a positive SLN
      when conventional H&E and IHC staining was performed. Patients with preoperative
      breast biopsy showed a 1.37 times (95% CI, 1.13-1.66) increased risk of SLN
      metastases on univariate analysis, but this result was not persistent when
      analysis was adjusted for other relevant factors for axillary node metastases, OR
      1.09 (95% CI, 0.85-1.40). In addition, subgroup analyses of the risk for occult
      micro metastases to the SLN (detected by IHC only) on H&E-negative cases also
      showed no increased risk associated with preoperative biopsy, OR 1.07 (95% CI,
      0.69-1.65). The conclusion, based on the present data, is that preoperative
      breast biopsy does not cause artificial tumour cell spread to the SLN, with
      possible negative impact on the prognosis of breast cancer.

PMID- 15477860
TI  - Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle
      encapsulated doxorubicin.
AB  - NK911 is a novel supramolecular nanocarrier designed for the enhanced delivery of
      doxorubicin (DXR) and is one of the successful polymer micelle systems to exhibit
      an efficient accumulation in solid tumours in mice. The purpose of this study was
      to define the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of
      NK911 and to evaluate its pharmacokinetic profile in man. NK911 was given
      intravenously to patients with solid tumours every 3 weeks using an infusion pump
      at a rate of 10 mg DXR equivalent min(-1). The starting dose was 6 mg DXR
      equivalent m(-2), and the dose was escalated according to the accelerated
      titration method. A total of 23 patients participated in this study. Neutropenia
      was the predominant haematological toxicity, and grade 3 or 4 neutropenia was
      observed at doses of 50 and 67 mg m(-2). Common nonhaematological toxicities were
      mild alopecia, stomatitis, and anorexia. In the dose identification part of the
      study, DLTs were observed at a dose of 67 mg m(-2) (grade 4 neutropenia lasting
      more than 5 days). Thus, this dosage level was determined to be the MTD. Infusion
      related reactions were not observed in any cases. The C(5 min) and area under the
      concentration curve parameters of NK911 exhibited dose-dependent characteristics.
      Among the 23 patients, a partial response was obtained in one patient with
      metastatic pancreatic cancer. NK911 was well tolerated and produced only moderate
      nausea and vomiting at myelosuppressive dosages. The recommended phase II dose
      was determined to be 50 mg m(-2) every 3 weeks.

PMID- 15477861
TI  - Birth weight is associated with postmenopausal breast cancer risk in Swedish
      women.
AB  - There is some evidence that birth weight is associated with breast cancer.
      Whether this association differs between premenopausal and postmenopausal ages is
      still unclear. The results from this study suggest that higher birth weight is a
      risk factor for postmenopausal breast cancer (OR 1.06, CI 1.00-1.12, per 100 g),
      independent of selected early-life and adult factors.

PMID- 15477862
TI  - BRCA1 mutations in ovarian cancer and borderline tumours in Norway: a nested case
      control study.
AB  - The aims of the present study were to find the frequency of the most common BRCA1
      mutations in women with ovarian tumours identified from a population-based cancer
      registry and in the general population, to estimate the relative risk of ovarian
      tumours among the mutation carriers, and to explore the value of using CA125 as a
      prediagnostic test. The study was designed as a nested case-control study within
      a cohort mainly consisting of participants in population-based health
      examinations. The data files of The Cancer Registry of Norway and the Janus serum
      bank were linked to identify cases with ovarian cancer and borderline tumours.
      Hereditary BRCA1 mutations were determined using archived serum samples and
      capillary electrophoresis. Altogether 478 ovarian cancer patients and 190
      patients with borderline tumours were identified, and 1421 and 568 matching
      controls were selected. Odds ratios (OR) of developing ovarian cancer and
      borderline tumours in the presence of BRCA1 mutations and CA125 level were
      derived from conditional logistic regression models. Among the 478 ovarian cancer
      patients, 19 BRCA1 mutations were identified (1675delA, 1135insA, 816delGT and
      3347delAG), none among the patients with borderline tumours. Only two of the 1989
      controls were BRCA1 mutation carriers (0.10%). The risk of ovarian cancer among
      the mutation carriers was strongly elevated (OR=29, 95% CI=6.6-120). CA125 was a
      marker for ovarian cancer, but the sensitivity was low. This study showed that
      BRCA1 mutation carriers have a very high risk of ovarian cancer. However, since
      the prevalence of BRCA1 mutations in the Norwegian population was low, the
      proportion of ovarian cancers due to BRCA1 mutations seemed to be low, about 4%.
      The sensitivity of using CA125 only as a screening test for ovarian cancer was
      low.

PMID- 15477863
TI  - Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1
      and -8 in human leukaemia cells.
AB  - Khat chewing is a widespread habit that has a deep-rooted sociocultural tradition
      in Africa and the Middle East. The biological effects of khat are inadequately
      investigated and controversial. For the first time, we show that an organic
      extract of khat induces a selective type of cell death having all morphological
      and biochemical features of apoptotic cell death. Khat extract was shown to
      contain the major alkaloid compounds cathinone and cathine. The compounds alone
      and in combination also induced apoptosis. Khat-induced apoptosis occurred
      synchronously in various human cell lines (HL-60, NB4, Jurkat) within 8 h of
      exposure. It was partially reversed after removal of khat and the effect was
      dependent on de novo protein synthesis, as demonstrated by cotreatment with
      cycloheximide. The cell death was blocked by the pan-caspase inhibitor Z-VAD-fmk,
      and also by submicromolar concentrations of Z-YVAD-fmk and Z-IETD-fmk, inhibitors
      of caspase-1 and -8, respectively. The 50% inhibition constant (IC(50)) for khat
      (200 microg ml(-1))-induced apoptosis by Z-VAD-fmk, Z-YVAD-fmk and Z-IETD-fmk was
      8 x 10(-7) M as compared to 2 x 10(-8) M and 8 x 10(-8) M, respectively. Western
      blot analysis showed a specific cleavage of procaspase-3 in apoptotic cells,
      which was inhibited by Z-VAD-fmk. The cell death by khat was more sensitively
      induced in leukaemia cell lines than in human peripheral blood leukocytes. It is
      concluded that khat induces a rather swift and sensitive cell death by apoptosis
      through mechanisms involving activation of caspase-1, -3 and -8.

PMID- 15477864
TI  - Surgery and adjuvant dendritic cell-based tumour vaccination for patients with
      relapsed malignant glioma, a feasibility study.
AB  - Patients with relapsed malignant glioma have a poor prognosis. We developed a
      strategy of vaccination using autologous mature dendritic cells loaded with
      autologous tumour homogenate. In total, 12 patients with a median age of 36 years
      (range: 11-78) were treated. All had relapsing malignant glioma. After surgery,
      vaccines were given at weeks 1 and 3, and later every 4 weeks. A median of 5
      (range: 2-7) vaccines was given. There were no serious adverse events except in
      one patient with gross residual tumour prior to vaccination, who repetitively
      developed vaccine-related peritumoral oedema. Minor toxicities were recorded in
      four out of 12 patients. In six patients with postoperative residual tumour,
      vaccination induced one stable disease during 8 weeks, and one partial response.
      Two of six patients with complete resection are in CCR for 3 years. Tumour
      vaccination for patients with relapsed malignant glioma is feasible and likely
      beneficial for patients with minimal residual tumour burden.

PMID- 15477865
TI  - Wild-type oestrogen receptor beta (ERbeta1) mRNA and protein expression in
      Tamoxifen-treated post-menopausal breast cancers.
AB  - This study has tested the hypothesis that comparison of protein and mRNA
      expression for ERalpha and ERbeta1 by human breast cancers provides novel
      information relating to the clinical and pathological characteristics of human
      breast cancers. Expression of ERalpha and ERbeta1 was identified in 167 invasive
      cancers from postmenopausal women treated only with endocrine therapy. The cohort
      included 143 cases receiving only adjuvant Tamoxifen following surgery. ERalpha
      and ERbeta1 expression was analysed by immunohistochemistry and reverse
      transcription RT-PCR and compared with clinical progression of individual
      cancers. ERalpha protein was closely associated with the corresponding RNA
      detected by RT-PCR (Chi-square, P<0.001). In contrast, ERbeta1 protein and mRNA
      were inconsistent. Although an association was identified between ERalpha and
      ERbeta mRNAs (Chi-square, P<0.001) and between ERalpha protein and ERbeta1 mRNA
      (Chi-square, P<0.027), no association was identified for the ERalpha and ERbeta1
      proteins detected by immunohistochemistry. ERbeta1 was not associated with
      outcome. However, in the absence of ERalpha, ERbeta1 protein expression was
      associated with elevated cell proliferation. There was a trend for the ERbeta1
      protein-positive cases to have a worse outcome, both within the group as a whole
      as well as within the ERalpha-positive Tamoxifen-treated cases. This study has
      confirmed the hypothesis that expression of ERalpha is an important determinant
      of breast cancer progression, and has further demonstrated that ERbeta1 may play
      a role in the response of breast cancers to endocrine therapy.

PMID- 15477866
TI  - Steroid-free medium discloses oestrogenic effects of the bisphosphonate
      clodronate on breast cancer cells.
AB  - Tamoxifen is the standard first-line endocrine therapy for breast cancer, but
      recent data indicate that it is likely to be replaced by the effective aromatase
      inhibitors (AIs), in both the metastatic and adjuvant settings. Aromatase
      inhibitors induce complete oestrogen deprivation that leads to clinically
      significant bone loss. Several ongoing or planned trials combine AIs with
      bisphosphonates, even more so that recent data reveal that clodronate may reduce
      the incidence of bone metastases and prolong survival in the adjuvant setting.
      Bisphosphonates can inhibit breast cancer cell growth in vitro, but they have
      never been studied in steroid-free medium (SFM), an in vitro environment that
      mimics the effects of AIs in vivo. Quite surprisingly, in SFM, clodronate
      stimulated MCF-7 cell growth in a time- and dose-dependent manner by up to two
      fold (crystal violet staining assay), whereas it had no mitogenic activity in
      complete medium. The bisphosphonate similarly increased the proliferation of IBEP
      2 cells, which also express a functional oestrogen receptor (ER), while it weakly
      inhibited the growth of the ER-negative MDA-MB-231 cells. Expectedly, 17beta
      oestradiol stimulated the growth of MCF-7 and IBEP-2 cells cultured in SFM, and
      had no effect on MDA-MB-231 cells. Moreover, partial (4-OH-tamoxifen) and pure
      antioestrogens (fulvestrant, ICI 182,780), in combination with clodronate,
      completely suppressed the mitogenic effect of the bisphosphonate, suggesting that
      it was mediated by an activation of ER. In accordance with this view, clodronate
      induced ER downregulation, weakly increased progesterone receptor expression, and
      stimulated the transcription of an oestrogen-responsive reporter gene. In
      conclusion, we report a previously unknown stimulatory effect of clodronate on
      MCF-7 cells grown in SFM, in vitro conditions that are potentially relevant to
      the use of AIs for breast cancer. Moreover, our data suggest that ER is involved
      in these effects of clodronate on cancer cell growth.

PMID- 15477867
TI  - Induction of proteasome expression in skeletal muscle is attenuated by inhibitors
      of NF-kappaB activation.
AB  - The potential for inhibitors of nuclear factor-kappaB (NF-kappaB) activation to
      act as inhibitors of muscle protein degradation in cancer cachexia has been
      evaluated both in vitro and in vivo. Activation of NF-kappaB is important in the
      induction of proteasome expression and protein degradation by the tumour factor,
      proteolysis-inducing factor (PIF), since the cell permeable NF-kappaB inhibitor
      SN50 (18 microM) attenuated the expression of 20S proteasome alpha-subunits, two
      subunits of the 19S regulator MSS1 and p42, and the ubiquitin-conjugating enzyme,
      E2(14k), as well as the decrease in myosin expression in murine myotubes. To
      assess the potential therapeutic benefit of NF-kappaB inhibitors on muscle
      atrophy in cancer cachexia, two potential inhibitors were employed; curcumin (50
      microM) and resveratrol (30 microM). Both agents completely attenuated total
      protein degradation in murine myotubes at all concentrations of PIF, and
      attenuated the PIF-induced increase in expression of the ubiquitin-proteasome
      proteolytic pathway, as determined by the 'chymotrypsin-like' enzyme activity,
      proteasome subunits and E2(14k). However, curcumin (150 and 300 mg kg(-1)) was
      ineffective in preventing weight loss and muscle protein degradation in mice
      bearing the MAC16 tumour, whereas resveratrol (1 mg kg(-1)) significantly
      attenuated weight loss and protein degradation in skeletal muscle, and produced a
      significant reduction in NF-kappaB DNA-binding activity. The inactivity of
      curcumin was probably due to a low bioavailability. These results suggest that
      agents which inhibit nuclear translocation of NF-kappaB may prove useful for the
      treatment of muscle wasting in cancer cachexia.

PMID- 15477868
TI  - Inverse relationship between ER-beta and SRC-1 predicts outcome in endocrine
      resistant breast cancer.
AB  - The oestrogen receptor (ER) interacts with coactivator proteins to modulate genes
      central to breast tumour progression. Oestrogen receptor is encoded for by two
      genes, ER-alpha and ER-beta. Although ER-alpha has been well characterized, the
      role of ER-beta as a prognostic indicator remains unresolved. To determine
      isoform-specific expression of ER and coexpression with activator proteins, we
      examined the expression and localisation of ER-alpha, ER-beta and the coactivator
      protein steroid receptor coactivator 1 (SRC-1) by immunohistochemistry and
      immunofluorescence in a cohort of human breast cancer patients (n=150). Relative
      levels of SRC-1 in primary breast cultures derived from patient tumours in the
      presence of beta-oestradiol and tamoxifen was assessed using Western blotting
      (n=14). Oestrogen receptor-beta protein expression was associated with disease
      free survival (DFS) and inversely associated with the expression of HER2
      (P=0.0008 and P<0.0001, respectively), whereas SRC-1 was negatively associated
      with DFS and positively correlated with HER2 (P<0.0001 and P<0.0001,
      respectively). Steroid receptor coactivator 1 protein expression was regulated in
      response to beta-oestradiol or tamoxifen in 57% of the primary tumour cell
      cultures. Protein expression of ER-beta and SRC-1 was inversely associated
      (P=0.0001). The association of ER-beta protein expression with increased DFS and
      its inverse relationship with SRC-1 suggests a role for these proteins in
      predicting outcome in breast cancer.

PMID- 15477869
TI  - Comparison of cancer survival in UK and Australia: rates are higher in Australia
      for three major sites.
AB  - Relative survival of patients diagnosed with cancers of the colorectum, lung and
      female breast from Yorkshire, UK and New South Wales (NSW), Australia in 1992
      2000 were compared using multiple regression models to adjust for various
      factors. Statistically significant differences were observed for all sites,
      Yorkshire patients having a 47-58% higher risk of excess death than those of NSW.

PMID- 15477870
TI  - Investigation of the DAOA/G30 locus in panic disorder.

PMID- 15477871
TI  - No support for association between dyslexia susceptibility 1 candidate 1 and
      developmental dyslexia.

PMID- 15477872
TI  - Neural activities associated with emotion recognition observed in men and women.
AB  - Previous studies have suggested that men and women process emotional stimuli
      differently. In this study, we examined if there would be any consistency in
      regions of activation in men and women when processing stimuli portraying happy
      or sad emotions presented in the form of facial expressions, scenes, and words. A
      blocked design BOLD functional magnetic resonance imaging paradigm was employed
      to monitor the neural activities of male and female healthy volunteers while they
      were presented with the experimental stimuli. The imaging data revealed that the
      right insula and left thalamus were consistently activated for men, but not
      women, during emotion recognition of all forms of stimuli studied. To further
      understand the imaging data acquired, we conducted the protocol analysis method
      to identify the cognitive processes engaged while the men and women were viewing
      the emotional stimuli and deciding whether they were happy or sad. The findings
      suggest that men rely on the recall of past emotional experiences to evaluate
      current emotional experiences. This may explain why the insula, a structure
      important for self-induced or internally generated recalled emotions, was
      consistently activated in men while processing emotional stimuli. Our findings
      suggest possible gender-related neural responses to emotional stimuli.

PMID- 15477873
TI  - Proteome analysis of prostate cancer.
AB  - In this paper, we briefly review cancer proteomics in general, with particular
      attention to our proteome analyses of prostate cancer. Our efforts include
      development of new tools and novel approaches to discovering proteins potentially
      useful as cancer diagnostic and/or prognostic biomarkers or as therapeutic
      targets. To this end, we analyzed prostate cancer proteomes using two-dimensional
      gel electrophoresis employing agarose gels for the initial isoelectric focusing
      step (agarose 2-DE), with mass spectrometry used for protein identification.
      Agarose 2-DE offers advantages over the more widely used immobilized pH gradient
      2-DE for separating high molecular mass proteins (15-500 kDa), thereby increasing
      its power to detect changes in the cancer's high-molecular mass proteomes.

PMID- 15477874
TI  - MUC1 expression in human prostate cancer cell lines and primary tumors.
AB  - MUC1 expression was evaluated in normal prostate epithelial cells (PrEC), and
      prostate cancer cell lines in response to dihydrotestosterone (DHT), interferon
      gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) treatment.
      Expression of MUC1 core protein was stimulated in PrEC and PC-3 cells after
      cytokine treatment, but was highly and constitutively expressed by DU-145 cells.
      MUC1 was not expressed by LNCaP, C4-2 or C4-2B cells under any condition. DHT
      alone or in combination with cytokines had no effect on MUC1 expression in any
      cell line tested. Using antibodies capable of detecting all isoforms of MUC1 core
      protein independent of their glycosylation state, immunohistochemical staining of
      tissue microarrays containing both nontumor and tumor tissue revealed that only
      17% of tumor tissues and 41% of nontumor tissues stained positively for MUC1.
      Staining patterns in tumor tissue varied from focal apical staining to diffuse
      cytoplasmic staining. Neither the presence of MUC1 core protein nor its
      subcellular distribution correlated with Gleason grade. These data indicate that
      MUC1 is a poor marker of prostate cancer progression. Furthermore, IFN-gamma and
      TNF-alpha strongly induce MUC1 expression in both normal prostate epithelia and
      certain prostate tumor cell lines and may exacerbate pathologies associated with
      MUC1-positive prostate cancers.

PMID- 15477875
TI  - Combining a targeted radiotherapy and gene therapy approach for adenocarcinoma of
      prostate.
AB  - A targeted radiotherapy/gene therapy approach for prostate cancer, using the
      radiopharmaceutical [(131)I]meta-iodobenzylguanidine ([(131)I]MIBG), would
      restrict the effects of radiotherapy to malignant cells, thereby increasing
      efficacy and decreasing morbidity of radiotherapy. Prostate cancer cells were
      transfected with a transgene encoding the noradrenaline transporter (NAT) under
      the control of tumour-specific telomerase promoters, enabling them to actively
      take up [(131)I]MIBG. This led to tumour-specific cell kill. This strategy has
      the advantage of generating a radiological bystander effect, leading to the
      destruction of neighbouring tumour cells that have escaped transfection. This
      targeted approach could be a promising tumour-specific treatment option for
      prostate cancer.

PMID- 15477876
TI  - Apoptotic regulators in prostatic intraepithelial neoplasia (PIN): value in
      prostate cancer detection and prevention.
AB  - Early diagnosis of prostate cancer holds tremendous promise for the effective
      therapy and impact on survival of prostate cancer patients. High-grade prostatic
      intraepithelial neoplasia (HGPIN) is generally accepted as a lesion indicative of
      a late pathological event in the premalignant changes leading to full development
      of prostate cancer. This review seeks to identify specific molecular events that
      may be linked directly to the molecular transition from benign prostate
      epithelial cells to prostate carcinoma. HGPIN is pathologically detected in a
      limited group of men undergoing prostate cancer screening for an elevated serum
      prostate-specific antigen (PSA) or abnormal digital rectal examination (DRE).
      Loss of apoptotic control provides a molecular basis for the contribution of
      specific defective steps in the pathway towards development and progression of
      prostate cancer. Comparative dissection of the apoptosis status and expression
      profile of key apoptotic regulators among foci of highly proliferative benign
      prostatic epithelium, PIN and prostate adenocarcinoma from adjacent areas of the
      same gland revealed a novel insight into the dysfunctional apoptosis events
      contributing to prostate carcinogenesis. The sequential and notable loss of the
      three critical signaling components of the apoptotic action of transforming
      growth factor-beta (TGF-beta), in the prostate, that is, the transmembrane
      receptor II (TbetaRII), the key cell cycle inhibitor p27(Kip1), as well as the
      protagonist downstream effector of the TGF-beta signaling mechanism, Smad4,
      points to their potential value to 'faithfully' characterize HGPIN, as a
      premalignant prostate lesion. Recent evidence on the molecular changes in
      apoptosis regulators contributing to HGPIN and their role as molecular markers of
      disease onset, as well as candidates for therapeutic targeting/chemoprevention of
      prostate cancer in its early stages will be discussed.

PMID- 15477877
TI  - Serum sex steroid hormone levels and polymorphisms of CYP17 and SRD5A2:
      implication for prostate cancer risk.
AB  - Polymorphism of the steroid hormone-related genes might affect life-long androgen
      exposure, thus altering a risk of prostate cancer incidence. To evaluate the
      effect of the polymorphisms of CYP17 and SRD5A2 on serum steroid hormone levels,
      the 164 male Japanese cohort were tested for serum hormone levels and the
      genotype of the polymorphisms of CYP17 (T-C base substitution in the promoter
      region) and SRD5A2 (V89L). The linear trends across the CYP17 genotypes in serum
      free testosterone and androstenedione levels were found, suggesting the
      importance of the polymorphism of CYP17 in determining the circulating androgen
      levels.

PMID- 15477878
TI  - MRI of epidermoid cyst of the conus medullaris.
AB  - STUDY DESIGN: A case report of an epidermoid cyst in the conus medullaris with
      characteristic magnetic resonance imaging (MRI) findings. OBJECTIVE: To describe
      an epidermoid cyst in the conus medullaris with characteristic MRI findings and
      point out these findings that correlated well with histologic findings. SETTING:
      Taiwan. CASE REPORT: A 49-year-old man who suffered from pain and weakness in his
      right leg for 16 years. MRI showed a heterogeneous signal mass in the conus
      medullaris. The hyperintense signal area within the lesion may be attributed to
      the keratin content, whereas the hypointense signal area was related to
      calcification and soft-tissue component. The histologic findings were compatible
      with an epidermoid cyst. CONCLUSION: Epidermoid cysts in the conus medullaris
      must be considered in the differential diagnosis of mass lesions with long
      duration of related symptoms. The characteristic MRI findings are useful to
      differentiate epidermoid cysts from other tumors.

PMID- 15477879
TI  - [Disease production as business idea].

PMID- 15477880
TI  - [Employer as a gatekeeper for insurance?].

PMID- 15477881
TI  - [Difficult decisions related to death of children].

PMID- 15477882
TI  - [Norwegian Functional Scale--a new instrument in sickness certification and
      disability assessments].
AB  - BACKGROUND: Functional assessments are requested in the follow-up of sick-listed
      persons and for disability benefit decisions. We describe the development of the
      Norwegian Functional Scale that may assist health providers in getting an insight
      into patients' self-evaluated functioning. MATERIAL AND METHODS: An expert panel
      developed a 40-item functional scale to be completed by sick-listed persons. The
      scale was based on the WHO Classification of Functioning, Disability, and Health
      (ICF). In April 2001 the scale, SF-36, and COOP/WONCA charts were tested on 798
      persons who had been sick-listed for six weeks. Factor analysis was used to group
      single items into functional dimensions. Correlation analysis was applied for
      validity testing against the established instruments. RESULTS: 48% filled in the
      questionnaire. The factor analysis confirmed four physical dimensions of
      functioning (walking/standing, holding/handling, lifting/carrying and sitting),
      and three mental (coping, communicating and senses). The scale correlated
      significantly with corresponding dimensions in SF-36, COOP/WONCA and a question
      on ability to go back to work. INTERPRETATION: The Norwegian Functional Scale
      showed considerably reduced functioning in sick-listed persons. The scale appears
      to be valid.

PMID- 15477883
TI  - [Fibromyalgia--effect of exercise].
AB  - BACKGROUND: Fibromyalgia is a chronic widespread unexplained musculoskeletal pain
      syndrome with decreased pain threshold. Because the etiology of fibromyalgia is
      unknown and the pathogenesis is unidentified, treatment is largely symptomatic
      and not standardised. The pain and fatigue reported by individuals with
      fibromyalgia results in a relative sedentary lifestyle, hence also a decrease in
      the fitness level of skeletal muscles. MATERIAL AND METHODS: In order to assess
      the effect of exercise in fibromyalgia, the Cochrane Controlled Trials Register
      was reviewed; 17 studies of exercise interventions on cardiorespiratory
      endurance, muscle strength and/or flexibility were selected. RESULTS: The results
      from the studies are inconsistent but low-intensity aerobic exercise regimens
      were found to be one of the few effective treatments. In these studies, however,
      subjective pain levels fail to show significant improvement, although
      improvements are seen on other parameters such as improvement in the number of
      tender points, in total myalgic scores and reduced tender point tenderness,
      improved aerobic capacity, physical function, subjective well-being and self
      efficacy. INTERPRETATION: The group exercises varied from 1-3 times per week,
      sessions from 25 minutes to 90 minutes; the duration of the programmes from 6
      weeks to 6 month. Most of the programmes were low-intensity dynamic endurance
      training with a working rate at 50-70 % of maximal heart rate in relation to age.

PMID- 15477884
TI  - [Cell cycle-targeted therapy].
AB  - BACKGROUND: The cell cycle defines sequential molecular processes that ensure
      orderly cell division. The progression throughout the cell cycle is governed by
      cyclin-dependent kinases, each of which is enzymatically active solely upon
      binding to its specific cyclin. The cell cycle harbours two checkpoints, or
      surveillance posts, which are activated when DNA is damaged. The response to the
      DNA damage involves a temporary cell cycle arrest, mediated by cell cycle
      inhibitors or other enzyme proteins, ultimately leading to the outcome of cell
      survival if the DNA is properly repaired, or cell death. The cell cycle
      checkpoints may also be biological targets for new therapeutic strategies in
      cancer intervention. MATERIAL AND METHODS: We compared the effect of ionising
      radiation on tumour cells with intact or defective functions of the cell cycle
      checkpoint that governs cell division. RESULTS: The tumour cells responded to
      radiation-induced DNA damage by cell cycle arrest that required intact checkpoint
      function. This defence response was overridden upon treatment of the tumour cells
      with a checkpoint signalling inhibitor. INTERPRETATION: Several pharmacological
      compounds designed to experimentally target the cell cycle are currently in the
      pipeline for testing in early-phase clinical trials and may have therapeutic
      potential as radiosensitizers.

PMID- 15477885
TI  - [Withdrawal of treatment in severely ill newborn infants].
AB  - BACKGROUND: Improvements in diagnostics and treatment in perinatal medicine have
      enabled us to save more premature and critically ill infants and infants born
      with severe congenital anomalies. However, some of these children often develop
      complications with a poor prognosis both for survival and quality of life. An
      active decision to withdraw treatment is common practice in such cases. Little is
      known about the impact of this problem in neonatal care in Norway. MATERIAL AND
      METHODS: The records of 178 infants admitted as newborns and who died in our
      hospital during the period 1990-1999 were reviewed and analysed according to
      these groups: death in spite of full treatment, death because of active
      withdrawal of treatment, and death after palliative treatment. We also evaluated
      to what extent the parents were involved in the decision making process and how
      that process was documented in patient records. RESULTS: Death after withdrawal
      of treatment was identified in 65% of the cases and was mainly seen in critically
      ill immature and premature infants (74%). The parents were usually involved in
      the decision, though documentation in patient records of the decision making
      process was generally poor. The ethical, legal and practical implications of this
      state of affairs probably need to be reviewed.

PMID- 15477886
TI  - [Paediatric neurology and habilitation in Norway].
AB  - BACKGROUND: Based on results from a national survey we discuss the status and
      prospects of Norwegian child neurology and habilitation. MATERIAL AND METHODS: A
      questionnaire on neurology and habilitation was sent to all 22 Norwegian
      departments of paediatrics. RESULTS: All departments responded. The organisation
      of services varied considerably. Only one department registered children admitted
      for neurological disorders specifically. Habilitation was mainly based on out
      patient services. The number of out-patient neurology consultations in relation
      to regional population varied with a factor of 5.3 from the department with
      lowest to the one with highest number of cases. Corresponding factors were 5.9
      for number of habilitation consultations per year, 3.6 for paediatricians in
      child neurology and habilitation, and 5.6 for allied health professionals working
      in habilitation units. In Norway there were 61 physicians working in child
      neurology and habilitation. Several departments were active in work on
      methodology. Research was mainly carried out in university departments.
      INTERPRETATION: Child neurology and habilitation services are available in all
      Norwegian counties. There is need for more systematic registration of clinical
      activities, for research, including the effect of treatment and interventions,
      more work on methodology, more posts for graduate medical education in the field,
      better organisation of services for in-patients, and closer cooperation between
      paediatric, habilitation and community care services.

PMID- 15477887
TI  - [Are young Norwegian women sufficiently physically active?].
AB  - BACKGROUND: The physical activity level of girls and young women is not known in
      Norway, hence the aim of this survey was to study physical activity and compare
      it with national recommendations for physical activity. MATERIAL AND METHODS: A
      questionnaire including the International Physical Activity Questionnaire (IPAQ)
      was administered to a representative sample of women aged 13-39 years (n=900).
      The response rate was 69%; 549 women were included in the study. RESULTS: The
      physical activity level and intensity of exercise decreased with increasing age.
      52 % percent of those aged 13-19 met the recommendations for adolescents: at
      least one hour of activity per day, including walking or other activities of at
      least moderate intensity. 63% percent of women in the age group 20-39 were
      physically active during the last week, on average at least 30 minutes every day
      at moderate intensity. In the age bracket 20-29 and 30-39 years, 72%, and 57%,
      respectively met the recommendations. INTERPRETATION: The activity level
      decreased with increasing age. Every second adolescent girl and four in ten young
      women were not as physically active as recommended.

PMID- 15477888
TI  - [Is teleradiology service in primary health care cost-effective?].
AB  - BACKGROUND: Not many analyses have been performed of the cost-effectiveness of
      telemedicine services. A teleradiology service linking a general practice in
      rural Norway up with the local hospital in the nearest town was established in
      1998. METHODS: Savings on traveling expenditure were registered for all patients
      who underwent elective examinations in Otta during the first year of service.
      Over a four-month period in 2002, records were made of whether patients
      undergoing emergency examinations were taken in to the local general practice or
      referred to the hospital. These data are key factors in the evaluation of cost
      effectiveness. The method employed is a cost-minimisation analysis in which the
      costs of teleradiology are compared to the costs incurred when patients go to
      hospital for a radiological examination. RESULTS: On the basis of data for 3006
      patients, an estimated annual NOK 1.4 million (USD 200,000) were saved on
      travelling expenditures and by patients or their employers because of working
      hours not lost. Annual costs of NOK 50,000 were avoided because radiological
      examinations in the surgical out-patient clinic are no longer necessary. Annual
      costs of NOK 400,000 include investments in equipment, lease of a broadband
      connection, and less efficient utilization of equipment and surgeries.
      Examinations done twice incurred estimated annual costs of NOK 40,000. The cost
      minimization analysis shows that on an annual basis the service saves costs of
      NOK 1 million (USD 160,000). INTERPRETATION: This study shows that telemedicine
      is most likely to be cost-effective when annual patient load and travel costs are
      high, together with relatively low investment costs.

PMID- 15477889
TI  - [Withdrawal syndrome after treatment with antidepressive agents].

PMID- 15477890
TI  - [High-dose treatment with autologous stem cell support in a Norwegian region].
AB  - BACKGROUND: The introduction of high-dose treatment with autologous stem cell
      support (HMAS) in Norwegian regional hospitals in the early 1990s was
      controversial. Concerns that low numbers of patients would lead to unacceptably
      low quality were expressed. MATERIAL AND METHODS: We present treatment results in
      the health region of Middle Norway, based on nearly 10 years of experience and
      100 treated patients. Myeloma results are compared to the results from other
      Norwegian regional hospitals. RESULTS AND INTERPRETATION: Overall survival for
      multiple myeloma after HMAS (median 6.8 years) was not significantly different in
      middle Norway compared to the rest of the country, and comparable with published
      results. Treatment-related mortality was low (1.2%). Results and complications in
      malignant lymphoma, breast cancer or germ cell tumours are described. HMAS can be
      satisfactorily given in a regional hospital with relatively few patients.

PMID- 15477891
TI  - [Organ donation, elective ventilation and ethics].

PMID- 15477893
TI  - [Just a little incision].

PMID- 15477895
TI  - [Should cerebral angiography still be required in organ donation?].

PMID- 15477896
TI  - [ICF--a new international classification of functions and health].

PMID- 15477897
TI  - [Physicians' professional secrecy].

PMID- 15477898
TI  - [Therapeutic gap when it comes to behavioral symptoms and psychoses among the
      elderly].

PMID- 15477902
TI  - [Inguinal hernia surgery in adult men].

PMID- 15477904
TI  - [Karl Popper and the cholesterol hypothesis].

PMID- 15477905
TI  - Circumstances and consequences of falls in residential care: the New Zealand
      story.
AB  - AIMS: To describe the circumstances and consequences of falls in long-term
      residential care homes in New Zealand. METHODS: A study followed 14 residential
      care facilities over 18 months and recorded all falls experienced by 680
      residents (97% participation rate). The number and characteristics of falls are
      described according to the timing, activities, direction, and severity of falls.
      Predictors of injury are examined using regression techniques. RESULTS: 271
      residents sustained 954 falls, 63% of which resulted in injury. The rate of falls
      increased in the afternoons especially in rest homes. Environmental hazards were
      involved with 15% of falls. Falling in the dining room was associated with fewer
      injuries, and falling from a standing height, and to the side, were independently
      associated with major injury such as hip fracture. CONCLUSION: The timing and
      circumstances of observed falls and their subsequent injuries is useful
      information for healthcare planners, and staff involved in the care of older
      people living in long-term residential care settings.

PMID- 15477906
TI  - Assessment prior to institutional care: time to move past the Support Needs
      Assessment Form (SNAF).

PMID- 15477907
TI  - Responding to partner abuse: understanding its consequences, and recognising the
      global and historical context.

PMID- 15477908
TI  - Recognising and responding to partner abuse: challenging the key facts.
AB  - Inter-partner violence is a serious public health problem for a minority of the
      population. Frequently the problem is hidden and goes undetected. Recognising
      this violence within the primary healthcare setting and responding appropriately
      are laudable aims, with significant health gains. However it is important that in
      raising professional and public awareness of the issue, the case is not over
      stated. Too often figures such as a NZ$141 million annual cost of family violence
      to health are quoted and presented as 'fact' without critical appraisal. Family
      violence is an emotional topic, and challenge to prevailing viewpoints may be
      misconstrued as a denial of the problem. These are important issues, and I invite
      academic debate.

PMID- 15477909
TI  - Risk factors for entry into residential care after a support-needs assessment.
AB  - AIMS: To establish the influence of risk factors derived from the national
      'Support Needs Assessment Form' for entry into residential care in New Zealand.
      METHODS: Using a retrospective cohort design, data was obtained for assessments
      of people aged over 65 years over a 12-month interval (August 2001 to August
      2002) from an administrative database developed by the Needs Assessment and
      Service Co-ordination Service for Wellington, New Zealand. The risk factors for
      entry into residential care were examined by logistic regression. RESULTS: 2060
      assessments were carried out over this period for people were aged over 65 years;
      67.9% were female. The median age was 83 years, inter-quartile range 78 to 88
      years. For 33.4% of people, residential care was recommended. For those aged 80
      years or older, the relative risk of residential care was 2.95 (95% CI: 2.27 to
      3.82) if continence problems were present, and 3.75 (95% CI: 2.99 to 4.73) for
      those aged 80 years or younger if continence problems were present. For those
      with mobility problems who had cognitive impairment the relative risk of
      residential care was 2.95 (95% CI: 2.25 to 3.87), and 1.77 (95% CI: 1.35 to 2.33)
      if there were no mobility problems. CONCLUSIONS: All of older age, continence
      problems, mobility problems and dementia predicted residential care after
      assessment. The effect of continence was more prominent for those aged under 80
      years of age. The effect of dementia was more prominent for those with mobility
      problems. Intervention for continence problems and mobility problems has the
      potential to reduce the use of residential care.

PMID- 15477910
TI  - General Practice care of enduring mental health problems: an evaluation of the
      Wellington Mental Health Liaison Service.
AB  - AIMS: To describe the development and evaluation of a primary care service for a
      population of mental health consumers who had previously been predominantly cared
      for by a specialist service. METHODS: Consumers were interviewed at regular
      intervals after entry to the programme. The Health of the Nation Outcomes Scale
      (HoNOS) and the Life Skills Profile (LSP) outcomes measures were used with
      consumers at intervals of 0,3,6,12 and 18 months after entry to the programme. A
      cost comparison was made between services provided to consumers in the year
      before entry to the programme, and after entry. RESULTS: Consumers reported no
      deterioration in their clinical condition while under the care of general
      practitioners, and they were largely satisfied with general practitioner care.
      Consumers' LSP scores were stable after entry to the programme. General
      practitioners were initially ambivalent about the programme, but were more
      supportive after 12 months had elapsed. The education provided to general
      practitioners, nurses, and receptionists was strongly welcomed. CONCLUSIONS: With
      carefully designed training and support, general practice can provide high
      quality community-based mental healthcare for consumers with enduring mental
      health disorders, and it can support the introduction of integrated mental health
      care initiatives.

PMID- 15477911
TI  - Diurnal, weekly, and seasonal variations in stroke occurrence in a population
      based study in Auckland, New Zealand.
AB  - AIMS: To determine (via a population-based study in Auckland, New Zealand) if
      there are diurnal, weekly, or seasonal variations in the occurrence of stroke.
      METHODS: All new stroke events in Auckland residents were traced. Time of onset
      of the stroke was defined as the time when neurological symptoms were first
      noticed. The day of the week and month of onset were analysed for all strokes.
      RESULTS: 1711 patients were registered over 1 year. The rate ratios for the onset
      of stroke in each 6-hourly interval compared with reference interval (1800-2359
      hours) were 0.74 (95% CI: 0.61-1.10) for 0000-0559 hours, 2.88 (95% CI: 2.48
      3.34) for 0600-1159 hours and 1.74 (95% CI: 1.49-2.05) for 1200-1759 hours. Rate
      ratios of the seasonal occurrence of stroke compared with spring were 0.75 (95%
      CI: 0.65-0.86) for summer, 0.83 (95% CI: 0.73-0.95) for autumn and 1.08 (95% CI:
      0.96-1.23) for winter. No weekly pattern of stroke occurrence was observed.
      CONCLUSIONS: Strokes were less likely to occur during the summer and autumn than
      in the winter or spring. There was an increase in the occurrence of stroke in the
      late morning. The results have implications for the provision of acute stroke
      services in the community and in hospital.

PMID- 15477912
TI  - Under-reporting of energy intake in the 1997 National Nutrition Survey.
AB  - AIMS: To estimate the level of under-reporting of energy intake by gender, age,
      ethnicity and body size (normal, overweight, obese) in the 1997 National
      Nutrition Survey (NNS97) in New Zealand. METHODS: Data were from 4,258
      participants (1,808 men and 2,450 women aged 15 years and over) who completed the
      24-hour diet recall; the primary methodology used in the NNS97. Under-reporting
      was assessed using the ratio of reported energy intake to estimated resting
      metabolic rate (EI: RMRest). Cut-off limits were used to identify percentages of
      under-reporters in the various subgroups. RESULTS: Mean EI: RMRest was 1.40 for
      all participants (1.51 for men, 1.30 for women, p<0.001) with older age being
      associated with lower EI: RMRest (p<0.001). There were no significant differences
      in mean EI: RMRest between ethnic groups for men. Mean EI: RMRest for women were:
      Maori 1.46, European 1.29, and Pacific 1.37 (p<0.01). A larger body size was
      associated with a significantly lower EI: RMRest especially for women.
      Percentages of 'definite' under-reporters (individual EI: RMRest <0.9) were as
      follows: men 12%, women 21%; Europeans 16%, Maori 23% and Pacific 26%; normal
      weight (11%), overweight (19%) and obese (27%) participants; and from 10% in the
      youngest to 23% in the oldest age group (p<0.001 for all results). CONCLUSION: In
      this study, in agreement with the literature, women, older people and obese
      people under-reported more than men, younger people and non-obese people.
      Possible ethnic differences in under-reporting rates need further study. Care is
      needed in interpreting the energy intake data from the NNS97.

PMID- 15477913
TI  - Doctors, elder abuse, and enduring powers of attorney.
AB  - There is widespread ignorance among doctors and other professionals dealing with
      incapacitated patients, about the scope and nature of powers granted when an
      enduring power of attorney is donated. This article discusses some of the
      shortcomings in the legislation contained in Part IX of the Protection of
      Personal and Property Rights Act (1988), and the appropriate course of action for
      those who think that attorneys are misusing their powers and failing to act in
      the best interests of incapacitated patients.

PMID- 15477914
TI  - Erysipelothrix rhusopathiae causing infective endocarditis in a female patient
      requiring valve replacement.

PMID- 15477915
TI  - Looking back at the 1987 Cervical Cancer Inquiry.

PMID- 15477916
TI  - Operative rates for acute intussusception in New Zealand.

PMID- 15477918
TI  - Medical image. Chilaiditi's Syndrome.

PMID- 15477919
TI  - Rheumatologic diagnostic serology: tests which test clinicians.

PMID- 15477920
TI  - The end of the one-eyed surgeon? Time for more randomised controlled trials of
      surgical procedures.

PMID- 15477921
TI  - Anti-cyclic citrullinated antibodies: complementary to IgM rheumatoid factor in
      the early diagnosis of rheumatoid arthritis.
AB  - AIMS: To compare the diagnostic sensitivity of anti-cyclic citrullinated (CCP)
      antibodies and rheumatoid factor (RF) in rheumatoid arthritis (RA) within a
      general hospital setting. METHOD: Using the American College of Rheumatology
      (ACR) classification criteria as a gold standard, the frequency of RF and anti
      CCP antibody positivity was compared between two groups of RA patients: those
      with disease duration less than 2 years (early RA, ERA) and those with disease
      duration more than 2 years (late RA, LRA). RESULTS: In ERA, the diagnostic
      sensitivity of RF and anti-CCP antibodies was 57% and 79% respectively. In LRA,
      it was 81% and 84% respectively. CONCLUSION: Anti-CCP antibodies are 20% more
      sensitivity than RF in the diagnosis of early RA.

PMID- 15477922
TI  - The burden of rheumatic disorders in general practice: consultation rates for
      rheumatic disease and the relationship to age, ethnicity, and small-area
      deprivation.
AB  - AIMS: To estimate the burden of rheumatic disorders in the New Zealand population
      by calculating general-practice consultation rates--as well as the influence of
      age, gender, ethnicity, and small-area deprivation on these consultation rates.
      METHODS: Cases were identified from the Royal New Zealand College of General
      Practitioners database using search-strings of typical words used in consultation
      notes (for each of 10 rheumatic disorders). Rates were calculated from a
      denominator of the number of people attending at least once over a 12-month
      period to any of 22 contributing general practices. The independent effect of
      age, sex, ethnicity, and small-area deprivation was modelled using multiple
      logistic regression. RESULTS: Of 29,152 people attending their general
      practitioner, 20.4% consulted with a rheumatic disorder. Older people, males,
      people who lived in more deprived areas, and Europeans were more likely to
      consult with a rheumatic disorder. With all rheumatic disorders, age was a
      significant influence upon consultation--especially osteoarthritis, gout,
      osteoporosis, and joint surgery. Maori were more likely than Europeans to consult
      with gout, but they were slightly less likely to consult with back pain or
      regional pain disorders. Small-area deprivation had small influences upon people
      consulting with gout, regional pain, and back pain. CONCLUSIONS: Rheumatic
      disorders form a significant part of the workload of general practitioners and
      this is significantly influenced by local demographic factors. Most of these
      conditions seen in general practice are non-inflammatory and non-surgical. If a
      community-needs approach was taken, it is likely that the workload and associated
      costs would be even greater.

PMID- 15477923
TI  - Low back pain in young New Zealanders.
AB  - AIMS: To describe the occupational implications and impact of low back pain (LBP)
      in a birth cohort now aged 26. METHODS: The LBP data were collected by an
      interviewer-administered questionnaire. Study members were asked about the
      prevalence and frequency of LBP and, for the worst episode, details were sought
      on occupation, time off work or job limitation, the severity of the discomfort,
      and disability. RESULTS: The cohort comprised 980 individuals, and 969
      individuals answered the questionnaire. Of these 969 individuals, 524 (54%)
      experienced LBP in the previous 12 months, with a modal frequency of three or
      more times a year. For the 448 individuals with a current occupation, there was
      no difference in the distribution of LBP between those with professional,
      clerical, and technical jobs and those with production or trades jobs. Fifty-six
      individuals had to have time off work (the majority for less than 7 days), and 13
      individuals could not look after themselves because of pain. Based on data
      gathered on 26 year olds, the cost to the economy is estimated as NZ500 million
      dollars per annum. CONCLUSION: LBP is prevalent and disabling even in young
      people, and has high costs. The natural history of the disorder is still largely
      unknown, but work does play a part. Although getting a person back to work may
      still be the best treatment, it is important to address the workplace factors.

PMID- 15477924
TI  - Ruptured abdominal aortic aneurysms: risk factors for mortality after emergency
      repair.
AB  - AIMS: Emergency repair for ruptured aneurysm is associated with a high mortality
      rate. From our experience of treatment of ruptured abdominal aortic aneurysms
      (AAA), we evaluated the morbidity and mortality rates, and identified
      preoperative variables that may be predictive of mortality after emergency
      repair. METHODS: Retrospective review of 41 patients who had emergency ruptured
      AAAs repair during July 1996 to April 2002 in Middlemore Hospital, Auckland, New
      Zealand. Demographic, preoperative, intraoperative, and postoperative data were
      recorded and statistically analysed to identify predictors for mortality.
      RESULTS: The mean age of the population was 72.9 years (range 57-89 years).
      Fifteen percent of patients died during the operation, and 26% died
      postoperatively. Bleeding was the most common cause of postoperative death (45%),
      followed by myocardial infarction (36%) and multisystem organ failure (27%). The
      overall surgical mortality rate was 41%. Serum creatinine of > or =0.15, age > or
      =80 years, 3 or more medical comorbidities and preoperative hypotension (systolic
      <90 mmHg) were identified to be significant risk factors for mortality (p<0.05)
      by univariate analysis. Serum creatinine of > or =0.15 mmol/L was the only
      variable multivariately (plt;0.05) associated with mortality with an odds ratio
      of 9.3. CONCLUSIONS: Selection of patients with ruptured AAAs for emergency
      repair can be a complex and emotionally charged process. Simple preoperative
      variables with predictive values have been identified, which may be used to
      complement the surgeon's own patient selection criteria for emergency repair.

PMID- 15477925
TI  - Percutaneous vertebroplasty for osteoporotic fracture: preliminary experience at
      Middlemore Hospital.
AB  - AIMS: To describe our initial experience with percutaneous vertebroplasty in a
      New Zealand teaching hospital setting. METHODS: Five patients suffering
      osteoporotic vertebral fractures were treated with percutaneous vertebroplasty.
      RESULTS: Three patients experienced improvement in pain after the procedure. The
      other two experienced documented improvement in mobility. There were no
      significant complications. DISCUSSION: This small series shows that percutaneous
      vertebroplasty has been successfully performed in a New Zealand teaching
      hospital. The definitive role of this technique in the management of patients
      with osteoporotic fractures remains to be determined.

PMID- 15477926
TI  - The role of ERCP in management of retained bile duct stones after laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Retained bile duct stones after cholecystectomy are an established
      entity. To find out the incidence of retained common bile duct (CBD) stones after
      laparoscopic cholecystectomy (LC) in our hospital, we conducted a retrospective
      study of patients who presented with symptomatic retained stones in the biliary
      system after a LC. METHODS: Between the period 1992-2000, 824 LCs were performed
      in our hospital. Twenty-five of these returned to the hospital with symptoms and
      signs suggestive of CBD stones. RESULTS: Prior to LC, ultrasound scans of all the
      patients showed gall stones. Alanine transaminase (ALT) was raised in 15
      patients. All of these patients underwent LC. On readmission, ALT was raised in
      20 patients, bilirubin was raised in 9 patients, and alkaline phosphatase (ALK)
      was raised in 16 patients. Ultrasound showed common bile duct dilatations in 16
      patients, with 6 of these dilated bile ducts having stones. All 25 patients
      underwent endoscopic retrograde cholangiopancreatography (ERCP)--with successful
      removal of stones in 16 cases, failure in 5 cases, and no stones in 4 cases. A
      second ERCP was successful in removing stones in 4 of the 5 failed patients.
      CONCLUSIONS: In our hospital, the incidence of symptomatic retained stones after
      a LC is about 2.5%. Ultrasound is poor in visualising common bile duct stones
      although it detects CBD dilatations in majority of cases (76%). ERCP is an
      effective technique for diagnosis and treatment of retained post-LC stones, with
      minimum morbidity and no mortality in our small series.

PMID- 15477927
TI  - Angiosarcoma in father and son: a case report and literature review.

PMID- 15477928
TI  - Stapled haemorrhoidectomy--no pain, no gain?
AB  - Stapled anopexy/haemorrhoidectomy (SH) was introduced in 1993 and first described
      by Longo in 1998. In New Zealand, more than 700 stapled haemorrhoidectomies have
      been performed. The procedure is one of the most studied of all recent new
      surgical technologies, and the literature is surveyed in this paper to assess the
      procedure's safety and efficacy. From review of the current literature is seems
      appropriate to conclude that SH is a safe procedure. It is probably not the
      answer for all haemorrhoids, especially those that are extremely large or are
      associated with a very significant external component. The procedure certainly
      has a sound theoretical basis and is likely here to stay. Patients like it
      because it is less painful than conventional techniques but they need to be
      counselled that its durability is not known.

PMID- 15477929
TI  - The bioavailability of coenzyme Q10 supplements available in New Zealand differs
      markedly.

PMID- 15477930
TI  - Performance indicators: primary health, secondary care, and diabetes.

PMID- 15477996
TI  - Skeletal phenotype of growing transgenic mice that express a function-perturbing
      form of beta1 integrin in osteoblasts.
AB  - Skeletal modeling entails the deposition of large amounts of extracellular matrix
      (ECM) to form structures tailored to withstand increasing mechanical loads during
      rapid growth. Specific ECM molecules bind to integrin receptors on the cell
      surface, thereby triggering a cascade of signaling events that affect critical
      cell functions. To evaluate the role of integrins during skeletal growth,
      transgenic mice were engineered to express a function-perturbing fragment of
      beta1 integrin consisting of the transmembrane domain and cytoplasmic tail under
      the control of the osteocalcin promoter (TG mice). Thus, transgene expression was
      targeted to mature cells of the osteoblast lineage, and herein we show that
      cultured cells resembling osteocytes from 90-day-old TG mice display impaired
      adhesion to collagen I, a ligand for beta1 integrin. To determine the influence
      of beta1 integrin on bones that are responsible for providing structural support
      during periods of rapid growth, we examined the phenotype of the appendicular
      skeleton in TG mice compared to wild type (WT) mice. According to radiographs,
      bones from mice of both genotypes between 14 and 90 days of age appeared similar
      in gross structure and density, although proximal tibiae from 35-90 days old TG
      mice were less curved than those of WT mice (72-92% TG/WT). Although there were
      only mild and transient differences in absolute bone mass and strength, once
      normalized to body mass, the tibial dry mass (79.1% TG/WT females), ash mass
      (78.5% TG/WT females), and femoral strength in torsion (71.6% TG/WT females) were
      reduced in TG mice compared to WT mice at 90 days of age. Similar effects of
      genotype on bone mass and curvature were observed in 1-year-old retired breeders,
      indicating that these phenotypic differences between TG and WT mice were stable
      well into adulthood. Effects of genotype on histomorphometric indices of
      cancellous bone turnover were minimal and evident only transiently during growth,
      but when present they demonstrated differences in osteoblast rather than
      osteoclast parameters. Together, these results suggest that integrin signals
      generated during growth enhance the acquisition of a skeletal mass, structure,
      and strength to withstand the mechanical loads generated by weight-bearing.

PMID- 15477997
TI  - Tooth quality in dental fluorosis genetic and environmental factors.
AB  - Dental fluorosis (DF) affects the appearance and structure of tooth enamel and
      can occur following ingestion of excess fluoride during critical periods of
      amelogenesis. This tooth malformation may, depending on its severity, influence
      enamel and dentin microhardness and dentin mineralization. Poor correlation
      between tooth fluoride (F) concentration and DF severity was shown in some
      studies, but even when a correlation was present, tooth fluoride concentration
      explained very little of DF severity. This fact calls into question the generally
      accepted hypothesis that the main factor responsible for DF severity is tooth
      fluoride concentration. It has been shown previously that genetic factors
      (susceptibility to DF) play an important role in DF severity although DF severity
      relates to individual susceptibility to fluoride exposure (genetics), tooth
      fluoride concentration relates to fluoride ingestion (environmental). The
      objective of this study was to investigate the correlation between tooth fluoride
      concentration, DF severity, and tooth mechanical and materials properties. Three
      strains of mice (previously shown to have different susceptibility to DF) at
      weaning were treated with four different levels of F in their water (0, 25, 50,
      and 100 ppm) for 6 weeks. Mice teeth were tested for fluoride by instrumental
      neutron activation analysis (INAA), DF severity determined by quantitative light
      induced fluorescence [QLF], and tooth quality (enamel and dentin microhardness
      and dentin mineralization). Tooth fluoride concentration (environment factor)
      correlated positively with DF severity (QLF) (rs=0.608), fluoride treatment group
      (rs=0.952). However, tooth fluoride concentration correlated negatively with
      enamel microhardness (rs=-0.587), dentin microhardness (rs=-0.268) and dentin
      mineralization (rs=-0.245). Dental fluorosis (genetic factor) severity (QLF)
      correlated positively with fluoride treatment (rs=0.608) and tooth fluoride
      concentration (rs=0.583). DF severity correlated negatively with enamel
      microhardness (rs=-0.564) and dentin microhardness (rs=-0.356). Genetic factors
      (DF severity) and the environmental factor (fluoride concentration in tooth
      structure) have similar influence on tooth biomechanical properties, whereas only
      the environmental factor has an influence on tooth material property
      (mineralization).

PMID- 15477998
TI  - Role of zinc in regulation of protein tyrosine phosphatase activity in
      osteoblastic MC3T3-E1 cells: zinc modulation of insulin-like growth factor-I's
      effect.
AB  - Zinc, an essential trace element, has been demonstrated to stimulate bone growth
      in animal and human. The cellular mechanism by which zinc stimulates bone growth
      has not been fully clarified. The effect of hormone and zinc on protein tyrosine
      phosphatase activity in osteoblastic MC3T3-E1 cells was investigated. Cells were
      cultured for 72 h in medium containing 10% fetal bovine serum (FBS) to obtain
      subconfluent monolayers, and then exchanged to culture medium containing either
      vehicle, zinc sulfate or various hormones in the absence of 10% FBS. After medium
      change, cells were cultured for 48 h. Protein tyrosine phosphatase activity in
      the lysate of cells was significantly increased by culture with zinc (10(-6) -
      10(-4) M). The effect of zinc in increasing the enzyme activity was completely
      blocked by culture with cycloheximide (10(-7 )M), an inhibitor of protein
      synthesis, or 5, 6-dichloro-l-beta-D- riboifuranosylbenzimidarzole (DRB) (10(-6)
      M), an inhibitor of translational activity. Addition of calcium chloride (10
      microM) into the reaction mixture caused a significant increase in protein
      tyrosine phosphatase activity; this increase was completely blocked in the
      presence of trifluoperazine (50 microM), an antagonist of calmodulin. Culture
      with zinc caused a significant increase in Ca2+/calmodulin-dependent protein
      tyrosine phosphatase activity in osteoblastic cells. Protein tyrosine phosphatase
      activity was significantly raised by culture with parathyroid hormone (human PTH
      [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,
      23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33]; 10(-7) M), 17beta-estradiol (10(-7)
      M), insulin-like growth factor-I (IGF-I; 10(-8) M) or insulin (10(-8) M). The
      enzyme activity was not significantly enhanced by the addition of calcium (10
      microM) into the reaction mixture. The effect of PTH or IGF-I in increasing
      protein tyrosine phosphatase activity was completely blocked by culture with DRB.
      The IGF-I-induced increase in enzyme activity was significantly enhanced by
      culture with zinc. Such an effect was not seen in the case of PTH. Moreover, the
      effect of IGF-I in increasing proliferation of osteoblastic cells was
      significantly enhanced by culture with zinc. The effect of PTH was not enhanced
      by zinc. This study demonstrates that protein tyrosine phosphatase activity in
      osteoblastic cells is enhanced by various bone anabolic factors, and that zinc
      modulates the effect of IGF-I on protein tyrosine phosphatase activity and cell
      proliferation.

PMID- 15477999
TI  - Differences in the fusion and resorption activity of human osteoclasts after
      stimulation with different growth factors released from a polylactide carrier.
AB  - Previous in vivo studies were able to demonstrate the efficacy of locally
      released growth factors IGF-I, TGF-beta1, and BMP-2 from a poly(D,L-lactide)
      (PDLLA) implant coating on fracture healing. In vitro studies using human
      osteoblast-like cells showed an enhanced collagen-1 production due to growth
      factor application without an effect of the PDLLA on the investigated parameter.
      Both bone-forming osteoblasts and bone-resorbing osteoclasts are important during
      bone formation and fracture healing. The aim of this study was to investigate the
      influence of different growth factors and the polylactide coating into which they
      were incorporated on isolated osteoclasts. In vitro studies using human
      osteoclast-like cells derived from peripheral blood mononuclear cells (PBMNCs)
      were performed. Titanium K-wires coated with the lactide loaded with IGF-I and
      TGF-beta1 (alone and in combination) or BMP-2 were added to the culture in a non
      contact manner and the fusion, resorption activity (pit formation assay), and
      TRAP 5b synthesis of the cells were analyzed. Differences in the effect of the
      growth factors were seen depending on the differentiation state of the cells. The
      fusion of the monocytes to multinuclear osteoclasts was significantly enhanced by
      the application of TGF-beta1 both alone and in combination with IGF-I. No effect
      was seen after application of IGF-I alone or BMP-2. The resorption activity of
      the osteoclasts analyzed on dentine chips was significantly enhanced after
      application of TGF-beta1 or BMP-2. These results indicate a differentiation
      dependent effect of growth factors on osteoclasts. TGF-beta1 affects both the
      osteoclastogenesis and the activity of osteoclasts, whereas BMP-2 had an effect
      only on the activity of mature osteoclasts but not on the fusion of the PBMNCs.

PMID- 15478000
TI  - Five years of treatment with risedronate and its effects on bone safety in women
      with postmenopausal osteoporosis.
AB  - We have recently reported that risedronate preserves normal bone formation and
      decreases bone remodeling in women with postmenopausal osteoporosis after 3 years
      of treatment. We report now the results of a 2-year extension study. The primary
      objective of this study was to determine the effect of 5 years of risedronate
      treatment (5 mg daily) on bone quality and bone remodeling based on paired
      transiliac bone biopsies. There were additional measurements that included bone
      turnover markers and bone mineral density (BMD). Histologic evaluation of biopsy
      sections (placebo, n = 21; risedronate, n = 27) yielded no pathologic findings
      after 5 years in either treatment group. Histomorphometric assessment of paired
      biopsy specimens after 5 years (placebo, n =12; risedronate, n = 13) found no
      statistically significant differences between treatment groups in structural or
      resorption parameters. There was a significant reduction in osteoid (-27%) and
      mineralizing surfaces (-49%) from baseline values in the risedronate group that
      were also significantly different from placebo at 5 years. Similarly, activation
      frequency decreased significantly (-77%) in the risedronate group, although it
      was not significantly different from placebo at 5 years (0.09 vs. 0.21,
      respectively). Double tetracycline labels were identified in all biopsy specimens
      indicating continuous bone turnover. After 5 years of risedronate treatment,
      serum bone-specific alkaline phosphatase (bone ALP) and N-telopeptide (NTX)
      decreased significantly from baseline by 33.3% and 47.5%, respectively. In the
      placebo group, bone ALP decreased by 3.9% (P = NS), whereas NTX decreased by
      27.0% (P < 0.005). Lumbar spine BMD increased significantly in the risedronate
      group (9.2%), whereas no significant change was seen in the placebo group (
      0.26%). Risedronate was overall well tolerated; during the 2-year study extension
      nonvertebral fractures occurred in 7 patients in placebo and 2 patients in
      risedronate groups. The findings from this study are consistent with the
      antiremodeling effect of risedronate and support long-term bone safety and
      antifracture efficacy of risedronate treatment.

PMID- 15478001
TI  - Vitamin D insufficiency in internal medicine residents.
AB  - Medical residents may be vulnerable to low vitamin D status because of long work
      hours and lack of sun exposure. We conducted a prospective cohort study to
      measure serum 25-hydroxyvitamin D concentrations among internal medicine
      residents, document seasonal variation in vitamin D status, and assess risk
      factors for inadequate vitamin D stores. Dietary intake of calcium and vitamin D,
      lifestyle characteristics, and serum concentrations of 25(OH)-vitamin D and
      intact parathyroid hormone (iPTH) were measured in 35 resident volunteers before
      and after the winter season. A total of 63-69% of medical residents consumed <400
      IU/day of vitamin D; 61-67% consumed <1000 mg/day of calcium. Twenty-five (74%)
      had lower serum 25(OH)-vitamin D concentrations and 23 (68%) had higher serum
      iPTH in the spring than in the fall. Nine (26%) residents had serum
      concentrations of 25(OH)-vitamin D of <20 ng/mL in the fall; and sixteen (47%) in
      the spring. Seven residents (20%) had serum concentrations of 25(OH)-vitamin D of
      <20 ng/mL at both time-periods; Eighteen residents (51.4%) had 25(OH)-vitamin D
      levels of <20 ng/mL for at least one of the time-periods. Medical residents are
      at risk for hypovitaminosis D, particularly during the winter months and should
      be aware of the need to supplement their vitamin D stores. Insufficient vitamin D
      status and inadequate vitamin D intake may have long-term implications for bone
      health in these individuals. Increased educational efforts to promote healthy
      dietary and lifestyle choices that allow attainment and maintenance of skeletal
      health are appropriate in this population.

PMID- 15478002
TI  - Effects of tunicamycin, mannosamine, and other inhibitors of glycoprotein
      processing on skeletal alkaline phosphatase in human osteoblast-like cells.
AB  - Skeletal alkaline phosphatase (sALP) is a glycoprotein- approximately 20%
      carbohydrate by weight, with five presumptive sites for N-linked glycosylation,
      as well as a carboxy-terminal site for attachment of the glycolipid structure
      (glycosylphosphatidylinositol, GPI), which anchors sALP to the outer surface of
      osteoblasts. The current studies were intended to characterize the effects of
      inhibiting glycosylation and glycosyl-processing on the synthesis, plasma
      membrane attachment, cellular-extracellular distribution, and reaction kinetics
      of sALP in human osteosarcoma (SaOS-2) cells. sALP synthesis, glycosylation, and
      GPI-anchor attachment were assessed as total protein synthesis/immunospecific
      sALP synthesis, sialic acid content (i.e., wheat germ agglutinin precipitation),
      and insolubility (i.e., temperature-dependent phase-separation), respectively.
      sALP reaction kinetics were characterized by analysis of dose-dependent initial
      velocity data, with a phosphoryl substrate. The results of these studies revealed
      that the inhibition of either N-linked glycosylation or oligosaccharide synthesis
      for GPI-anchor addition could affect the synthesis and the distribution of sALP,
      but not the kinetics of the phosphatase reaction. Tunicamycin-which blocks N
      linked glycosylation by inhibiting core oligosaccharide synthesis-decreased cell
      layer protein and the total amount of sALP in the cells, while increasing the
      relative level of sALP in the cell-conditioned culture medium (CM, i.e., the
      amount of sALP released). These effects were attributed to dose- and time
      dependent decreases in sALP synthesis and N-linked glycosylation, and an increase
      in apoptotic cell death (P <0.001 for each). In contrast to the effects of
      tunicamycin on N-linked glycosylation, the effects of mannosamine, which inhibits
      GPI-anchor glycosylation/formation, included (1) an increase in cell layer
      protein; (2) decreases in sALP specific activity, in the cells and in the CM; and
      (3) increases in the percentages of both anchorless and wheat germ agglutinin
      (WGA)-soluble sALP in the medium, but not in the cells (P <0.005 for each). These
      effects of mannosamine were, presumably, a consequence of inhibiting the
      insertion/attachment of sALP to the outside of the plasma membrane surface.
      Neither mannosammine nor tunicamycin had any effect on the reaction kinetics of
      sALP or on the apparent affinity (the value of KM) for the phosphoryl substrate.

PMID- 15478003
TI  - Immunohistochemical characterization of rapid dentin formation induced by enamel
      matrix derivative.
AB  - The purpose of this study was to examine the pulpal expression of dentin-related
      proteins during enamel matrix derivative (EMD)-induced reparative dentin
      formation in a pulpotomy model in pig incisors. Pulpotomies were performed on 72
      lower incisors in 24 adult miniature swine. The exposed pulp tissue was treated
      with EMD or covered with a calcium hydroxide paste (Dycal). At predefined time
      points, ranging from 4 days to 12 weeks, experimental teeth were extracted and
      examined by use of light microscopy, and expression of dentin-related proteins in
      the pulps was investigated by immunohistochemistry, using antibodies against type
      I collagen, dentin sialoprotein (DSP), sheathlin, and EMD. In all EMD-treated
      teeth a substantial amount of reparative dentin formation was observed. The
      amount of reparative dentin in calcium hydroxide-treated teeth was significantly
      smaller than in EMD-treated teeth (P < 0.005) and was less effective in bridging
      the pulpal wounds. Immunohistochemistry demonstrated that enamel matrix proteins
      were present in detectable amounts at the application site for about 4 weeks.
      Moreover, the expression of proteins related to dentin formation in the wounded
      pulp tissue was about 2 weeks advanced in EMD-treated teeth. These findings
      demonstrate that enamel matrix molecules have the capacity to induce rapid pulpal
      wound healing in pulpotomized teeth, and suggest that the longevity and continued
      presence of enamel matrix macromolecules at the application site can be utilized
      to stimulate growth and repair of dentin over a period consistent with a
      favorable clinical outcome.

PMID- 15478006
TI  - American Chemical Society--228th National Meeting. Technical achievements in
      organic synthesis. 22-26 August 2004, Philadelphia, PA, USA.

PMID- 15478007
TI  - American Chemical Society--228th National Meeting. Wolfrom/Isbell New
      Investigator Award Symposium.

PMID- 15478008
TI  - American Chemical Society--228th National Meeting. Gamma-secretase inhibitors. 22
      26 August 2004, Philadelphia, PA, USA.

PMID- 15478009
TI  - American Chemical Society--228th National Meeting. Metabolism. 22-26 August 2004,
      Philadelphia, PA, USA.

PMID- 15478010
TI  - American Chemical Society--228th National Meeting. Neurological modulators. 22-26
      August 2004, Philadelphia, PA, USA.

PMID- 15478011
TI  - American Chemical Society--228th National Meeting. Inflammation. 22-26 August
      2004, Philadelphia, PA, USA.

PMID- 15478012
TI  - American Chemical Society--228th National Meeting. General oral presentations. 22
      26 August 2004, Philadelphia, PA, USA.

PMID- 15478013
TI  - European Respiratory Society--14th Annual Congress. 4-8 September 2004, Glasgow,
      UK.

PMID- 15478014
TI  - European Respiratory Society--14th Annual Congress. Drug highlights. 4-8
      September 2004, Glasgow, UK.

PMID- 15478015
TI  - Head and Neck Cancer--Sixth International Conference. 7-11 August 2004,
      Washington, DC, USA.

PMID- 15478016
TI  - Drug Discovery Technology 2004--IBC's Ninth Annual World Congress. 8-13 August
      2004, Boston, MA, USA.

PMID- 15478017
TI  - Clinical Pharmacology and Therapeutics 2004--Eighth World Congress. 1-6 August
      2004, Brisbane, Australia.

PMID- 15478018
TI  - Therapeutic prospects for bradykinin receptor agonists in the treatment of
      cardiovascular diseases.
AB  - Kinins are located in the vascular smooth muscle and the heart, and are the most
      potent biologically active polypeptides. Pharmacological studies of
      cardiovascular disorders, including hypertension, cardiac failure, ischemia,
      myocardial infarction and left ventricular hypertrophy, indicate that reduced
      activity of the local kallikrein-kinin system (KKS) may be instrumental in the
      induction of these disorders. The ability of kallikrein gene delivery and
      bradykinin (BK) B2 receptor agonists to produce a wide spectrum of beneficial
      effects make them excellent candidate therapies for the treatment of
      hypertension, and cardiovascular and renal diseases. In addition, strategies that
      activate kinin receptors may be applicable to the treatment of cardiovascular and
      renal disorders. However, one major challenge of this approach is the unanswered
      question of whether there is a sufficiently safe therapeutic index between the
      potential cardioprotective and pro-inflammatory effects following administration
      of BK B2 receptor agonists.

PMID- 15478019
TI  - Ralfinamide. Newron Pharmaceuticals.

PMID- 15478022
TI  - MR imaging of diabetic foot infection.
AB  - Infection of the foot is common, especially in the diabetic population. Over the
      past decade, magnetic resonance imaging (MRI) has become a 'gold standard' for
      evaluation of pedal infection. Therefore it is important for the radiologist to
      understand the MRI appearance of various manifestations of infection as well as
      conditions that may simulate infection, including neuropathic disease.

PMID- 15478023
TI  - Imaging of posttraumatic osteomyelitis.
AB  - Posttraumatic osteomyelitis frequently leads to an illness characterized by
      chronicity and recurrences. Bone changes themselves, developed during chronic
      infection, and orthopedic implants heavily influence the diagnostic value of the
      different imaging methods. Conventional radiography remains the cornerstone of
      imaging of acute and chronic osteomyelitis, but other modalities such as
      ultrasonography, radionuclide studies, computed tomography, and magnetic
      resonance imaging may be necessary. The values of the techniques in different
      clinical settings are described.

PMID- 15478024
TI  - Scintigraphic techniques for the diagnosis of infectious disease of the
      musculoskeletal system.
AB  - In imaging infectious diseases of the musculoskeletal system, the metabolic
      information provided by nuclear medicine studies complements the structural
      information of radiologic modalities. Often the diagnosis can be confirmed by
      combining the methods in a diagnostic algorithm. The decision about whether a
      single study is best depends on the clinical setting and the questions that
      require an answer. Whereas radiography, magnetic resonance imaging (MRI), and
      computed tomography (CT) usually focus on a single area, nuclear medicine imaging
      offers the advantage of whole body imaging. However, despite significant
      improvements it cannot approach the detailed anatomical visualization provided by
      MRI or CT. In most cases scintigraphy is a very sensitive (e.g., bone scan,
      positron emission tomography) and often quite specific tool (e.g., white blood
      cell scintigraphy). The metabolic information of the single scintigraphic
      procedure depends on the accumulation mechanism. For the work-up of infectious
      disorders different radiopharmaceuticals can be used, and the decision for the
      best modality should be tailored to the clinical question and the special
      pathophysiologic condition of the infection. This article describes the most
      common nuclear medicine studies and their clinical relevance in some infectious
      diseases.

PMID- 15478025
TI  - MR imaging of spinal infection.
AB  - Magnetic resonance (MR) imaging plays a pivotal role in the diagnosis and
      management of spinal infection, enjoying a high sensitivity and specificity. A
      thorough understanding of spinal anatomy and the physicochemical pathological
      processes associated with infection is a desirable prerequisite allowing accurate
      interpretation of the disease process. Apart from confirmation of the disease, MR
      imaging is also best suited to excluding multifocal spinal involvement and the
      detection/exclusion of complications. It plays an essential role in the decision
      making process concerning conservative versus surgical treatment and is also the
      best imaging method to monitor the effect of treatment. The MR features of
      infection confidently exclude tumor, degeneration, and so forth as the underlying
      process; differentiate pyogenic from granulomatous infections in most cases; and
      can suggest the rarer specific infective organisms.

PMID- 15478026
TI  - Parasitic and fungal disease of bones and joints.
AB  - Among the musculoskeletal infections, fungal and parasitic diseases are
      infrequent and may have a nonspecific imaging factor. The incidences of fungal
      and parasitic bone infections are related to geographic distribution, ethnic and
      nutritional factors, and occupation. Immunocompromise and ease of travel can lead
      to increased incidence. These are a group of chronic disorders, and delayed
      diagnosis is common because radiographs, computed tomography, isotope studies,
      and magnetic resonance imaging are useful but often do not have specific signs
      for determination of the causative infective fungal or parasitic organism.
      Definitive diagnosis is possible with a high index of clinical suspicion and
      aspiration.

PMID- 15478027
TI  - Chronic recurrent multifocal osteomyelitis.
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is a clinical entity distinct
      from bacterial osteomyelitis. It occurs mainly in children and adolescents and is
      characterized by a prolonged, fluctuating course with recurrent episodes of pain
      occurring over several years. CRMO is often multifocal and most often seen in
      tubular bones, the clavicle, and less frequently the spine and pelvic bones;
      other locations are rare. The radiographic appearance suggests subacute or
      chronic osteomyelitis. Histopathological and laboratory findings are nonspecific
      and bacterial culture is usually negative. CRMO is often diagnosed by exclusion
      of the two main differential diagnoses--bacterial infections and tumor--by
      assessing for a characteristic course and the findings by conventional
      radiography, if necessary supplemented by scintigraphy and/or magnetic resonance
      imaging (MRI). The MRI appearance of CRMO lesions in tubular bones and the spine
      is often rather characteristic and support the diagnosis. It is important to
      diagnose CRMO to avoid unnecessary diagnostic procedures and initiate an
      appropriate therapy.

PMID- 15478028
TI  - Imaging of osteomyelitis with special reference to children.
AB  - Infection of bone in children represents a diagnostic and therapeutic challenge
      to the pediatrician, the surgeon, the radiologist, and the pathologist. The
      pattern of manifestation varies and is dependent on the site of involvement, the
      initiating event, the infecting organism, and the acute or chronic nature of the
      illness. Early diagnosis allows prompt treatment, which can prevent many of the
      dreaded complications of this disease. Plain radiographs remain the initial
      imaging modality used in the diagnosis and differential diagnosis of
      osteomyelitis. However, with the advent of newer imaging techniques such as
      scintigraphy, ultrasonography, computed tomography, and magnetic resonance
      imaging, a higher degree of accuracy in diagnosis and definition of the extent of
      the disease has been achieved. The time interval between the onset of symptoms
      and diagnosis has also been significantly reduced. Although magnetic resonance
      imaging has the additional advantage of multiplanar capability, greater anatomic
      detail, and excellent soft tissue resolution, it is a relatively expensive
      technique, which somewhat limits its use. Following a brief review of the
      classification and pathophysiology of osteomyelitis, we have tried to elucidate
      the utility of various imaging modalities in the diagnosis of osteomyelitis in
      children, outlining their relative strengths and weaknesses. Certain entities
      specific to children and a brief review of differential diagnosis are also
      presented.

PMID- 15478031
TI  - Acromegaly and heart failure: revisions of the growth hormone/insulin-like growth
      factor axis and its relation to the cardiovascular system.
AB  - Cardiomyopathy is a major cause of death in overt acromegaly. Recent progress in
      research has increasingly revealed the molecular mechanisms concerning growth
      hormone and insulin-like growth factor in the development of heart failure. In
      this article, we propose mechanisms according to which heart failure occurs, and
      we aim to extrapolate this knowledge to more general processes involved in heart
      failure.

PMID- 15478030
TI  - Ghrelin and synthetic growth hormone secretagogues are cardioactive molecules
      with identities and differences.
AB  - Ghrelin, a 28-amino acid peptide mainly produced by the stomach, is a natural
      ligand of the type 1a growth hormone secretagogue receptor (GHS-R1a) that also
      binds synthetic peptidyl and nonpeptidyl GHSs. GHS-R1a and various GHS-R1a
      related receptor subtypes are widely distributed in central and peripheral
      tissues, particularly in the cardiovascular system. In agreement with this
      distribution of GHS-R, ghrelin and synthetic GHSs exert a wide spectrum of
      actions, including cardiac and vascular activities. Ghrelin, as well as peptidyl
      and nonpeptidyl GHSs, is able to increase cardiac performances both in animals
      and in humans and to exert protective effects on ischemia/reperfusion injury of
      isolated rat heart. Moreover, both ghrelin and synthetic GHSs have been shown as
      able to act as survival factors, protecting cardiomyocytes and endothelial cells
      from doxorubicin-induced apoptosis. Despite the fact that the neuroendocrine
      actions of ghrelin are dependent on its acylation in serine 3, these
      cardiovascular effects are exerted by unacylated as well as by acylated ghrelin.
      This evidence indicates that these actions are not likely to be mediated by a
      type 1a GHS-R, which, by definition, binds acylated ghrelin only. However,
      synthetic peptidyl GHSs, but not nonpeptidyl, and even ghrelin itself are able to
      reduce atherosclerotic lesion development in apolipoprotein-E-deficient mice.
      This action seems to be mediated by a specific receptor for synthetic peptidyl
      GHSs only, identified as CD36, a multifunctional B-type scavenger receptor
      involved in atherogenesis and mainly expressed in cardiomyocytes and
      microvascular endothelial cells. Thus, there are similarities, but also
      differences, between ghrelin and synthetic GHSs, in terms of cardiac actions that
      are likely to be related to the existence of multiple GHS-R subtypes that mediate
      the cardiovascular actions of the above substances. These actions indicate their
      potential pharmacotherapeutic implications in cardiovascular diseases.

PMID- 15478032
TI  - Cortisol, 11beta-hydroxysteroid dehydrogenases, and hypertension.
AB  - Hypersecretion of cortisol is associated with hypertension. In addition, an
      abnormal cortisol metabolism may play a role in the pathogenesis of hypertension.
      The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isozymes catalyze
      interconversion of cortisol and cortisone and play an important role in the
      regulation of the effects of cortisol. Activity of 11beta-HSD type 2, converting
      active cortisol in inactive cortisone, is crucial in preventing access of
      cortisol to the renal mineralocorticoid receptors (MRs). Decreased activity of
      this isozyme in the kidney, either congenitally in Apparent Mineralocorticoid
      Excess syndrome or acquired following licorice consumption, allows cortisol
      access to the MRs, resulting in hypokalemic hypertension. In normotensive
      subjects, an association has been demonstrated between blood pressure increase on
      a high-salt diet and a mild decrease of renal 11beta-HSD2 activity. In ectopic
      adrenocorticotropic hormone (ACTH), plasma cortisol levels are very high,
      resulting in mineralocorticoid hypertension caused by saturation of the available
      renal 11beta-HSD2 capacity. Activity of the 11beta-HSDs has also been
      demonstrated in many extrarenal sites. Several studies have demonstrated
      extrarenal effects of cortisol on blood pressure, as well as a possible role for
      altered extrarenal 11beta-HSD activities in the pathogenesis of hypertension.
      More studies are needed to clarify the role of 11beta-HSDs in the pathogenesis of
      hypertension.

PMID- 15478033
TI  - Adrenomedullin: its role in the cardiovascular system.
AB  - Adrenomedullin is a 52-amino acid peptide that was first isolated from human
      pheochromocytoma. Subsequently, it was found to be distributed widely in the
      body, including throughout the cardiovascular system. It belongs to a family of
      peptides that include calcitonin gene-related peptide and amylin. Adrenomedullin
      causes vasorelaxation and influences vascular proliferation and interacts closely
      with nitric oxide, and it may have a role in the pathophysiology of hypertension,
      ischemic heart disease, and cardiac and renal failure. Nonpeptide agonists or
      antagonists of adrenomedullin may have potential therapeutic application. The
      role of adrenomedullin in septicemic shock also merits further investigation.

PMID- 15478034
TI  - The lost promise of hormone replacement therapy and heart disease.
AB  - Since the first secondary prevention trials were published in 1998, the prospect
      of hormone replacement therapy to prevent atherosclerotic heart disease in
      postmenopausal women has changed dramatically. Early harmful effects of hormone
      replacement therapy and lack of beneficial effects on coronary heart disease
      event rates in high-risk women have challenged the beneficial results gleaned
      from observational studies in the past. In this article, the effects of estrogens
      on lipids, hemostatic parameters, inflammation, and the vascular wall are
      described. The discrepancies that have arisen between the previous observational
      studies and recent randomized clinical trials are discussed: The current
      available data indicate that estrogens are beneficial to healthy endothelium but
      are harmful once atherosclerotic disease has developed.

PMID- 15478035
TI  - Hypothyroidism and cardiovascular disease: role of new risk factors and
      coagulation parameters.
AB  - Hypothyroidism is a common condition and recent epidemiological studies
      demonstrated that up to 10 percent of subjects may display its subclinical form.
      Despite the well-known relationship between overt hypothyroidism and
      cardiovascular disease, few studies demonstrating such a link are available.
      However, the relationship between hypothyroidism and a variety of cardiovascular
      risk factors is now well established. Recent data on new cardiovascular risk
      factors that were shown to be associated with hypotyroidism are reviewed.
      Haemostatic and fibrinolytic parameters are disturbed differently according to
      the stage of hypothyroidism. C-reactive protein levels are higher in patients
      with overt and subclinical hypotyroidism compared to euthyroid patients. In
      contrast, elevation of homocysteine values was demonstrated only in overt
      hypothyroidism. Although no randomized controlled trial evaluated the potential
      benefits of levothyroxine substitution on the risk to suffer major coronary
      events in patients with subclinical hypothyroidism, there is growing evidence
      that this disorder is mainly characterized by a high risk of cardiovascular
      disease.

PMID- 15478036
TI  - Cardiac saphenous vein bypass graft disease.
AB  - Coronary artery bypass grafting is an effective treatment for myocardial
      ischaemia and is particularly important in patients with multivessel disease and
      diabetes. However, up to 40% of saphenous vein grafts will occlude within 10
      years of surgery. The predominant mechanisms for saphenous vein graft disease are
      thrombosis, intimal hyperplasia, and accelerated atherosclerosis. The pathology
      of these changes and the role of key factors such as nitric oxide, cellular
      proliferation, and the role of hypercholesterolemia and hypertriglyceridaemia,
      are reviewed. Saphenous vein graft disease is among the first cardiovascular
      conditions to show significant benefit from gene therapy and promises to show
      remarkable developments in the near future.

PMID- 15478037
TI  - Depressive disorders and the metabolic syndrome of insulin resistance.
AB  - Metabolic syndrome of insulin resistance and depression are both considered
      important cardiovascular risk factors. The aim of this study was to ascertain a
      possible association between these conditions in a population sample of 116
      subjects (54 males, 62 females, aged 60 +/- 8 and 60 +/- 9 years, respectively).
      A standard questionnaire-the Hospital Anxiety Depression Scale-was used for the
      assessment of depressive disorder and clinical definition of insulin resistance,
      requiring the presence of three or more of the following factors: triglycerides >
      1.7 mmol/L; and high-density lipoprotein cholesterol < 1.0 mmol/L; blood pressure
      >/= 130/85 mm Hg; waist circumference > 102 cm in males and > 88 cm in females;
      fasting glucose 6.1-7.8 mmol/L. Depressive disorders prevailed significantly more
      in women than in men (39% and 26%, respectively), and prevalence of depression in
      subjects with metabolic syndrome of insulin resistance (by definition) was about
      four times higher than in subjects without depression. Depressive subjects had
      also higher heart rate, waist circumference, lower high-density lipoprotein
      cholesterol, higher triglycerides, and higher body mass index. Higher sympathetic
      nervous activity in insulin-resistant subjects with depression was indicated.

PMID- 15478038
TI  - The role of the somatotropic system in cognition and other cerebral functions.
AB  - Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) receptors can be
      found in several areas of the brain. GH receptors are mainly found in the choroid
      plexus, thalamus, hypothalamus, pituitary, putamen, and hippocampus, whereas IGF
      1 receptors are mainly concentrated in the hippocampus and parahippocampal areas.
      In early life, GH and IGF-1 have an important role in the development and
      differentiation of the central nervous system. In the more developed central
      nervous system, GH and IGF-1 are thought to have a variety of functions such as a
      neuroprotective function, an appetite increasing function, various cognitive
      functions, and perhaps a blood flow-regulating function. In GH-deficient children
      and adults, improvement of cognitive functions was observed after the
      administration of GH. Furthermore, specific cognitive functions in healthy older
      subjects may improve after increasing GH or IGF-1 levels.

PMID- 15478039
TI  - Drink to prevent: review on the cardioprotective mechanisms of alcohol and red
      wine polyphenols.
AB  - Moderate alcohol consumption has convincingly been associated with decreased
      cardiovascular mortality in epidemiological studies and metaanalyses. This
      decreased mortality has been attributed to changes in lipid profiles, decreased
      coagulation, increased fibrinolysis, inhibition of platelets, increased nitric
      oxide, and antioxidant capacities of alcoholic beverages. Most of these
      laboratory and animal studies, as well as small intervention trials in human
      volunteers, have revealed many interesting mechanisms that contribute to the
      cardioprotective effects of alcohol, red wine, or red wine polyphenolic
      compounds. An update on putative mechanisms is presented in this review.

PMID- 15478040
TI  - The emerging role of lipoproteins in atherogenesis: beyond LDL cholesterol.
AB  - Low-density lipoprotein cholesterol has a well-established role in atherogenesis
      and the development of coronary heart disease. However, despite effective
      lowering of low-density lipoprotein cholesterol, many patients continue to have
      cardiovascular events. It has subsequently emerged that several additional
      dyslipidemic states promote atherogenesis. In particular, the atherogenic
      lipoprotein phenotype comprising an elevation of triglycerides and triglyceride
      rich lipoproteins; decreased concentrations of high-density lipoprotein
      cholesterol; and increased small, dense low-density lipoprotein cholesterol, in
      addition to impaired postprandial lipemia, have been demonstrated to have
      profound effects on the arterial wall. As such, these factors have become
      important targets in the development of effective strategies to prevent
      atherosclerotic cardiovascular disease.

PMID- 15478041
TI  - Mechanistic insights and clinical relevance of the interaction between acute
      coronary syndromes and lipid metabolism.
AB  - As part of the acute phase reaction, lipid metabolism is significantly altered in
      patients with unstable coronary syndromes. The clinical relevance and the
      mechanisms underlying this phenomenon are discussed in this article. Cholesterol
      reduction takes place in the first hours of an acute coronary event; thus, plasma
      levels determined at this point should be interpreted with caution. This
      reduction may be just a consequence of the inflammatory response, or it may be
      also related to an increase in cellular uptake of cholesterol for tissue repair
      and hormonal synthesis. A synergistic effect between this predisposition to
      cholesterol reduction and statin therapy appears to exist during acute coronary
      syndromes. Triglyceride changes are variable during acute coronary syndromes, and
      recent data indicate that the pattern of triglyceride variation is a potential
      risk marker in those patients, possibly because it reflects neurohumoral changes
      related to the acute phase.

PMID- 15478042
TI  - Familial combined hyperlipidemia: controversial aspects of its diagnosis and
      pathogenesis.
AB  - Familial combined hyperlipidemia is the most frequent cause of primary
      dyslipidemia in Mexico. Its manifestations include hypercholesterolemia,
      hypertriglyceridemia, or a combination of both. Despite its high frequency, a
      proper diagnosis is rarely made. Assessment of the lipid profiles of at least
      three first-degree relatives is necessary. The diagnosis of familial combined
      hyperlipidemia in a family not only leads to the identification of other affected
      family members but, more important, allows cardiovascular risk stratification of
      those affected. Prospective studies have confirmed the atherogenicity of the
      disease. A critical review of the current literature in this field is presented
      in this article. Although three screenings of the genome have been completed, the
      genes responsible for this disorder have not been identified. Limitations with
      respect to the characterization of affected subjects and the heterogeneity of the
      disease are among possible explanations. However, familial combined
      hyperlipidemia, because of its high prevalence, must be given greater priority.
      It represents a great challenge for physicians involved in the treatment of
      dyslipidemic patients.

PMID- 15478043
TI  - Factors affecting plasma lipoprotein(a) levels: role of hormones and other
      nongenetic factors.
AB  - Lp(a) appears to be one of the most atherogenic lipoproteins. It consists of an
      low-density lipoprotein core in addition to a covalently bound glycoprotein,
      apo(a). Apo(a) exists in numerous polymorphic forms. The size of the polymorphism
      is mediated by the variable number of kringle-4 Type 2 repeats found in apo(a).
      Plasma Lp(a) levels are determined to more than 90% by genetic factors. Plasma
      Lp(a) levels in healthy individuals correlate significantly highly with apo(a)
      biosynthesis, and not with its catabolism. There are several hormones that are
      known to have a strong effect on Lp(a) metabolism. In certain diseases, such as
      kidney disease, the Lp(a) catabolism is impaired, leading to elevations that are
      up to a fivefold increase. Lp(a) levels rise with age but are otherwise only
      little influenced by diet and lifestyle. There is no safe and efficient way of
      treating individuals with elevated plasma Lp(a) concentrations. Most of the lipid
      lowering drugs have either no significant influence on Lp(a) or exhibit a
      variable effect in patients with different forms of primary and secondary
      hyperlipoproteinemia.

PMID- 15478044
TI  - High-density lipoprotein as a key component in the prevention of premature
      atherosclerotic disease in the insulin resistance syndrome.
AB  - The occurrence of insulin resistance syndrome (IRS), which is also called the
      metabolic syndrome, has rapidly increased over the last decade. IRS involves such
      major clinical features as premature atherosclerosis and its related
      complications. The major proatherogenic phenotype includes elevated plasma levels
      of apolipoprotein B-containing lipid particles. Another lipid particle of high
      density lipoprotein (HDL) plays a key role in the prevention of atherosclerotic
      disease. Decreased levels of HDL cholesterol are found in IRS; however, little is
      known about metabolic pathways related to HDL antiatherogenic properties in this
      pathological condition. Hitherto, in other dyslipidemic populations, the
      antiatherogenic properties of HDL have been most frequently characterized in
      vitro. Recently, knowledge about antiatherogenic pathways in which HDL particles
      are involved in vivo has been accumulating. Consistent with these developments,
      new therapeutic strategies can be envisaged for IRS, including treatment with
      recombinant HDL particles and inhibitors of cholesteryl ester transfer protein.

PMID- 15478045
TI  - [Treatment of severe preeclampsia and HELLP syndrome].
AB  - Severe preeclampsia and HELLP syndrome are still one of the leading causes of
      maternal and perinatal morbidity and mortality. The current definitions of the
      diseases should be considered before treatment. The timely allocation to a
      perinatal center and an intensive monitoring of mother and child after admission
      are mandatory for successful management of these patients. The aim of therapy is
      immediate stabilization of the mother's condition by means of anticonvulsive
      prophylaxis with intravenous magnesium sulphate, well-controlled reduction of
      blood pressure by the administration of urapidil or nifedipine, controlled volume
      expansion and an adequate treatment of coagulation disorders by giving fresh
      frozen plasma (not heparin). Immediate delivery is the method of choice in cases
      of severe preeclampsia/HELLP syndrome > or = 34 weeks' gestations; we prefer
      cesarean section in patients with an unripe cervix and the full-blown picture of
      HELLP syndrome. In patients < 34 weeks' gestation expectant management is
      generally possible under intensive monitoring of the mother and the fetus.
      Maternal and fetal indications for immediate termination of pregnancy should be
      considered carefully. The systemic application of corticosteroids is a promising
      approach to prolong pregnancy. During the past decade the increasing awareness of
      obstetricians and other disciplines have led to a significant reduction of
      maternal mortality (< 1 %) and perinatal mortality (9.4-16.2 %) in cases of HELLP
      syndrome, in particular in the West European countries.

PMID- 15478046
TI  - [New aspects in diagnosis and therapy of endometriosis].
AB  - Endometriosis and adenomyosis show a high prevalence and can be regarded as
      different symptoms of a unique disease - the dislocation of basal endometrium.
      Diagnostic methods for detecting adenomyosis are transvaginal sonography (TVS) or
      T-2-weighed magnetic resonance imaging (MRI). Patients with endometriosis show a
      significant impairment of utero-tubal sperm transport capacity, which is even
      increased the stronger the adenomyotic component of the disease is. Adenomyosis
      can be regarded as a cause for infertility especially in minor and mild forms of
      endometriosis and is therefore often followed by IVF/ICSI-treatment. Infertility
      patients with endometriosis should be counselled for intensive infertility
      treatment. Without a current wish for conception, fertility potential should be
      preserved by hormonal suppression of uterine peristalsis in order to avoid
      progression of the disease.

PMID- 15478047
TI  - [Management of breast cancer treatment -- a multidisciplinary approach].
AB  - The management of breast cancer care poses very high expectations on implementing
      the treatment recommendations and guidelines for diagnostic procedures into
      routine treatment. Most recently a majority of these tasks has been transferred
      to the responsibilities of the breast centers being established all over Germany
      these days. Guidelines on treatment and diagnostic procedures and minimal
      invasive techniques have therefore been discussed among 1 300 colleagues and
      experts at the Duesseldorfer Symposium in June 2004.

PMID- 15478048
TI  - [Treatment strategies for endometrial cancer].
AB  - This paper focuses on the controversies surrounding management of endometrial
      cancer, the most common carcinoma of the female genital tract. We discuss current
      management strategies, especially the importance of surgical staging and briefly
      describe ongoing prospective randomized trials. Actual treatment suggestions are
      attached as tables. Adenocarcinomas represent the majority of endometrial
      cancers. In contrast, papillary-serous and clear cell carcinomas comprise 1-10 %
      of endometrial cancers. While adenocarcinomas may well be treated by surgery and
      radiation therapy, identifying appropriate treatment modalities for patients with
      papillary-serous and clear cell carcinoma and poor prognosis is of critical
      importance. Data on radiation therapy or chemotherapy, to date, are of limited
      value secondary to small sample sizes and the heterogeneous treatment modalities
      that many times were applied. Individualized treatment strategies have to take
      into account accompanying co-morbidities, more importantly, though, whether the
      patient underwent surgical staging. Co-operative, prospective randomized trials
      across borders are needed more than ever to answer remaining questions.

PMID- 15478049
TI  - [First-line therapy in ovarian cancer].
AB  - Epithelial ovarian cancer is the gynecological tumor with the highest mortality
      rate. Recently, numerous new findings have emerged about status and extent of
      surgical therapy of this disease. Innovations regarding chemotherapy are also
      numerous. It is essential for the improvement of the patients' situation to
      transfer these new developments already implemented into national and
      international standards and guidelines to clinical practice.

PMID- 15478050
TI  - [Conventional and experimental prognostic factors in ovarian cancer].
AB  - Epithelial ovarian cancer is the leading cause of death from gynaecologic
      malignancies in western countries. In the clinical day treatment decision of the
      physician (e. g. surgery, chemotherapy) based on individual prognostic factors of
      the patient with ovarian cancer. The tumor stage at time of diagnosis and the
      postoperative residual tumor mass are prognostic factors and are unequivocally
      related to overall survival. Other prognostic factors are identified mostly in
      small series and are discussed in the literature controversially. This article
      discussing the value of conventional prognostic factors, as stage, postoperative
      tumor mass, age, lymph node status, ascites) and newer molecular biological
      factors, as Her-2-status, PAI-1, MMP, VEGF and CD24.

PMID- 15478051
TI  - The role of L1 in the progression of ovarian carcinomas.
AB  - The L1 molecule has recently emerged as a promising new biomarker for the
      prognosis of human ovarian and endometrial tumors. It was initially described as
      an adhesion molecule for the development of the nervous system but its function
      in tumor cells is not well known. In this article we summarize recent data on the
      role of L1 in promoting tumor cell adhesion and migration and in gene regulation.
      We address the question how L1 determination in tumor tissue samples and in serum
      and ascites could potentially improve the disease management.

PMID- 15478052
TI  - [Prognostic role and regulation of cyclooxygenase-2 (COX-2) in ovarian
      carcinoma].

PMID- 15478053
TI  - [Pregnancy-associated femoral nerve affection].
AB  - BACKGROUND: Common neuropathies during pregnancy are carpal tunnel syndrome or
      peripheral facial paralysis. However, there is little information about femoral
      nerve affection during pregnancy. CASE REPORT: We report on a female at 30 weeks
      of gestation, complaining of pain in hips and thighs and gait difficulty.
      Pregnancy was normally developed. Neurological examination showed a bilateral
      weakness in both quadriceps and iliopsoas muscles combined with soreness in hips
      and thighs, without deficits of sensibility. Laboratory findings and results of a
      lumbar punction were normal. Pelvic ultrasound and an MRI scan of the spine and
      pelvis showed no mass or disc prolaps. Neuromyographic evaluation bilaterally
      revealed acute signs of denervation of the muscles innervated by femoral nerve.
      Caesarean section was performed at 32 gestational weeks, as pain was unbearable
      and refractory to treatment with even opiates. Post partum, pain relieved
      immediately, and after weeks of physiotherapy, complete remission was achieved.
      CONCLUSION: This unusual manifestation of a neuropathy in pregnancy could be due
      to pressure on the femoral nerve. The patients' anxiety can be eliminated, as the
      described cases in literature show an excellent prognosis. However, the severity
      of symptoms can lead us to necessity of premature delivery.

PMID- 15478054
TI  - [End-to-end anastomosis in the primary repair of anal sphincter laceration
      occurring during delivery].
AB  - PURPOSE: To assess the quality of end-to-end anastomosis in the primary repair of
      anal sphincter laceration occurring during delivery. METHODS: Forty-nine women
      with third degree perineal laceration (PL III) and 42 controls were included in a
      3-year postpartal follow-up study. RESULTS: Ultrasound showed end-to-end
      anastomosis to be inadequate in 22 (48.1 %) women. Thirty-one (63.2 %) women
      developed grade I-III anal incontinence. DISCUSSION: There was no correlation
      between ultrasound findings and the presence of anal incontinence. The
      unsatisfactory sonomorphometric outcome after 6 weeks results from inadequate
      repair with retraction of the sphincter ends. Defects newly demonstrated after 36
      months indicate dedifferentiating atrophy with damage to peripheral motor nerves.

PMID- 15478055
TI  - Protection against clinical malaria by heterologous immunoglobulin G antibodies
      against malaria-infected erythrocyte variant surface antigens requires
      interaction with asymptomatic infections.
AB  - Erythrocytes infected with mature stages of Plasmodium falciparum express variant
      surface antigens (VSAs) of parasite origin, including P. falciparum erythrocyte
      membrane protein 1. Anti-VSA antibodies protect against clinical malaria caused
      by parasites bearing VSAs to which they are specific (homologous), but their role
      in protecting against heterologous infection is unclear. Here, we report that,
      among 256 Kenyan children involved in a 1-year active case surveillance study,
      asymptomatic parasitemia was associated with an enlarged repertoire of anti-VSA
      immunoglobulin G (IgG) antibodies specific to apparently heterologous parasite
      isolates, as measured by flow cytometry. Together, asymptomatic infection and
      anti-VSA IgG were associated with reduced odds of experiencing an episode of
      clinical malaria during follow-up, whereas, independently, they were associated
      with increased susceptibility. These results support previous findings and
      underline the importance of considering the parasitological status of study
      participants when examining the role that immune responses to VSAs and other
      malaria antigens play.

PMID- 15478056
TI  - Fosmidomycin-clindamycin for the treatment of Plasmodium falciparum malaria.
AB  - It has been demonstrated that fosmidomycin has good tolerability and rapid onset
      of action, but late recrudescences preclude its use alone; in vitro, clindamycin
      has been shown to act synergistically with fosmidomycin against Plasmodium
      falciparum. We conducted a study in pediatric outpatients with P. falciparum
      malaria in Gabon to evaluate the efficacy and safety of an oral combination of
      fosmidomycin-clindamycin of 30 mg/kg and 10 mg/kg of body weight, respectively,
      every 12 h. Patients 7-14 years old were recruited in cohorts of 10. The first 10
      patients were treated for 5 days. The duration of treatment was then
      incrementally shortened in intervals of 1 day if >85% of the patients in a cohort
      were cured by day 14. All dosing regimens were well tolerated, and no serious
      adverse events occurred. Asexual parasites and fever rapidly cleared in all
      patients. Cure ratios of 100% on day 14 were achieved with treatment durations of
      5 (10/10 patients), 4 (10/10 patients), 3 (10/10 patients), and 2 days (10/10
      patients); 1 day of treatment led to a cure ratio of 50% (5/10 patients).
      Fosmidomycin-clindamycin is safe and well tolerated, and short-course regimens
      achieved high efficacy in children with P. falciparum malaria. Fosmidomycin
      clindamycin is a promising novel treatment option for malaria.

PMID- 15478057
TI  - Screening for mutations related to atovaquone/proguanil resistance in treatment
      failures and other imported isolates of Plasmodium falciparum in Europe.
AB  - BACKGROUND: Two single-point mutations of the Plasmodium falciparum cytochrome b
      gene (Tyr268Asn and Tyr268Ser) were recently reported in cases of
      atovaquone/proguanil (Malarone) treatment failure. However, little is known about
      the prevalence of codon-268 mutations and their quantitative association with
      treatment failure. METHODS: We set out to assess the prevalence of codon-268
      mutations in P. falciparum isolates imported into Europe and to quantify their
      association with atovaquone/proguanil treatment failure. Isolates of P.
      falciparum collected by the European Network on Imported Infectious Disease
      Surveillance between April 2000 and August 2003 were analyzed for codon-268
      mutations, by use of polymerase chain reaction-restriction fragment-length
      polymorphism. RESULTS: We successfully screened 504 samples for the presence of
      either Tyr268Ser or Tyr268Asn. One case of Ser268 and no cases of Asn268 were
      detected. Therefore, we can be 95% confident that the prevalence of Ser268 in the
      European patient pool does not exceed 0.96% and that Asn268 is less frequent than
      0.77%. In 58 patients treated with atovaquone/proguanil, Tyr268Ser was present in
      1 of 5 patients with treatment failure but in 0 of 53 successfully treated
      patients. CONCLUSIONS: Tyr268Ser seems to be a sufficient, but not a necessary,
      cause for atovaquone/proguanil treatment failure. The prevalence of both codon
      268 mutations is currently unlikely to be >1% in the European patient pool.

PMID- 15478058
TI  - Genetic structure of Plasmodium falciparum populations in the Brazilian Amazon
      region.
AB  - After a major increase in incidence between the 1970s and the 1990s, the
      Brazilian Amazon region now accounts for the most cases of Plasmodium falciparum
      malaria in the Americas. Polymorphism of 10 microsatellite loci in the P.
      falciparum genome was studied in 196 isolates obtained from 5 populations in the
      region. There was significant multilocus linkage disequilibrium, particularly
      within populations with lower proportions of mixed-genotype infections. However,
      most multilocus genotypes in different isolates were distinct, and there was no
      evidence of any recent epidemic expansion of particular clones. Genetic
      divergence between populations was very substantial but did not fit a simple
      model of isolation by distance. Thus, different foci of P. falciparum in Brazil
      are quite independent, with distinct population structures and minimal gene flow,
      a finding that has implications for strategies to control infection and to
      contain the spread of drug resistance at a regional level.

PMID- 15478059
TI  - Antigenic drift in the ligand domain of Plasmodium vivax duffy binding protein
      confers resistance to inhibitory antibodies.
AB  - Interaction of the Duffy binding protein (DBP) with its erythrocyte receptor is
      critical for maintaining Plasmodium vivax blood-stage infections, making DBP an
      appealing vaccine candidate. The cysteine-rich region II is the ligand domain of
      DBP and a target of vaccine development. Interestingly, most of the allelic
      diversity observed in DBP is due to the high rate of nonsynonymous polymorphisms
      in this critical domain for receptor recognition. Similar to the hypervariability
      in influenza hemagglutinin, this pattern of polymorphisms in the DBP ligand
      domain suggests that this variation is a mechanism to evade antibody
      neutralization. To evaluate the role that dbp allelic diversity plays in strain
      specific immunity, we examined the ability of an anti-Sal1 DBP serum to inhibit
      the erythrocyte-binding function of variant dbp alleles expressed on COS cells.
      We observed that the PNG-7.18 allele was significantly less sensitive to immune
      inhibition of its erythrocyte-binding activity than were the Sal1 and PNG-27.16
      alleles. This result suggested that the unique polymorphisms of resistant PNG
      7.18 were part of a protective epitope on the DBP ligand. To confirm this, Sal1
      was converted to the refractory phenotype by introduction of 3 polymorphisms
      unique to PNG-7.18, via site-directed mutagenesis. The results of the present
      study indicate that linked polymorphisms have an additive, synergistic effect on
      DBP antigenic character.

PMID- 15478060
TI  - Seroepidemiology of infection with human papillomavirus 16, in men and women
      attending sexually transmitted disease clinics in the United States.
AB  - BACKGROUND: The study sought to characterize the seroprevalence, seropersistence,
      and seroincidence of human papillomavirus (HPV)-16 antibody, as well as the
      behavioral risk factors for HPV-16 seropositivity. METHODS: Serologic data at
      baseline and at 6- and 12-month follow-up visits were used to examine the
      seroprevalence, seropersistence, and seroincidence of HPV-16 antibody in 1595
      patients attending United States clinics treating sexually transmitted disease.
      Testing for antibody to HPV-16 was performed by capture enzyme-linked
      immunosorbent assay (ELISA) using viruslike particles. RESULTS: The
      seroprevalence of HPV-16 antibody was 24.5% overall and was higher in women than
      in men (30.2% vs. 18.7%, respectively). In those who were HPV-16 seropositive at
      baseline, antibody response persisted to 12 months in 72.5% of women and in 45.6%
      of men. The seroincidence of HPV-16 antibody was 20.2/100 person-years (py)
      overall, 25.4/100 py in women, and 15.7/100 py in men. In multivariate analysis,
      the seroprevalence of HPV-16 antibody was significantly associated with female
      sex, age >20 years, and the number of episodes of sex with occasional partners
      during the preceding 3 months, whereas the seroincidence of HPV-16 antibody was
      significantly associated with female sex, age >20 years, baseline negative ELISA
      result greater than the median value, and the number of episodes of unprotected
      sex with occasional partners during the preceding 3 months. CONCLUSION: Sex- and
      age-related differences in both the seropositivity and seroincidence of HPV-16
      antibody persisted after adjustment for behavioral and sociodemographic risk
      factors, and behavioral risk factors during the preceding 3 months were stronger
      predictors of the seroprevalence and seroincidence of HPV-16 antibody than was
      lifetime sexual behavior.

PMID- 15478061
TI  - Viral polymorphism in human papillomavirus types 33 and 35 and persistent and
      transient infection in the genital tract of women.
AB  - BACKGROUND: Genetic polymorphism in human papillomavirus (HPV)-33 and -35 was
      investigated in 1055 sexually active women (732 human immunodeficiency virus
      [HIV] seropositive and 323 HIV seronegative). METHODS: Consecutive genital
      specimens obtained at 6-month intervals were screened for HPV-33 and -35 by use
      of MY09-MY11. HPV-33 and -35 isolates from 95 women were analyzed by polymerase
      chain reaction sequencing of the long control region (LCR), E6, and E7. RESULTS:
      For HPV-33, 101 (20%) of 506 nucleotides in the LCR were variable, compared with
      10 (2.1%) of 483 nucleotides in E6 (P<.001) and 6 (1.9%) of 324 nucleotides in E7
      (P<.001). For HPV-35, the proportion of variable nucleotide sites was similar
      between the LCR and both E6 (P=.54) and E7 (P=.33). The presence of a 78-base
      pair deletion in HPV-33 (relative risk [RR], 1.8 [95% confidence interval [CI],
      1.2-2.7]) and the presence of nonsynonymous E7 variations in HPV-35 (RR, 2.6 [95%
      CI, 1.4-4.6]) were associated with persistence. When the data for HPV-33 and -35
      were combined, infection by HPV isolates with nonsynonymous E7 variations (RR,
      2.3 [95% CI, 1.6-3.4]; P=.001) and ethnicity (P=.04) were associated with
      persistence, whereas age (P = .14) and HIV infection/CD4 cell count status
      (P=.12) were not significantly associated with persistence, by logistic
      regression analysis. CONCLUSION: HPV-33 and -35 polymorphism was different
      between types and was associated with persistence of HPV infection.

PMID- 15478062
TI  - Molecular epidemiology of hepatitis C virus in a social network of injection drug
      users.
AB  - BACKGROUND: We aimed to measure the overlap between the social networks of
      injection drug users (IDUs) and the patterns of related hepatitis C virus (HCV)
      infections among IDUs. METHODS: A cohort of 199 IDUs (138 of whom were HCV RNA
      positive) was recruited from a local drug scene in Melbourne, Australia, and was
      studied using social network analysis and molecular phylogenetic analysis of 2
      regions of the HCV genome. RESULTS: Eighteen clusters of related infections
      involving 51 IDUs (37.0% of HCV RNA-positive IDUs) were detected; these clusters
      could be separated into 66 discrete pairs. Twelve (18.2%) of the 66 IDU pairs
      with related infections reported having previously injected drugs together;
      conversely, only 12 (3.8%) of the 313 pairs of HCV RNA-positive IDUs who were
      injection partners had strong molecular evidence of related infections. The
      social and genetic distances that separated IDUs with identical genotypes were
      weakly associated. Significant clusters of phylogenetically related sequences
      identified from core region analysis persisted in the analysis of the
      nonstructural 5a protein region. Genotyping and sequence analysis revealed 2
      mixed-genotype infections. CONCLUSIONS: Static social network methods are likely
      to gather information about a minority of patterns of HCV transmission, because
      of the difficulty of determining historical infection pathways in an established
      social network of IDUs. Nevertheless, molecular epidemiological methods
      identified clusters of IDUs with related viruses and provided information about
      mixed-genotype infection status.

PMID- 15478063
TI  - Control of Epstein-Barr virus load and lymphoproliferative disease by maintenance
      of CD8+ T lymphocytes in the T lymphocyte-depleted graft after bone marrow
      transplantation.
AB  - Of 100 bone marrow transplant recipients, 30 (30%) received a CD4(+) lymphocyte
      depleted graft (1x10(6) CD8(+) T lymphocytes/kg of body weight). Replication of
      Epstein-Barr virus (EBV) was observed in 40 patients (40%). The use of a CD4(+)
      lymphocyte-depleted graft was the only independent risk factor for replication of
      EBV (relative risk, 11.5; 95% confidence interval, 5.8-22.8; P<.0001).
      Nevertheless, EBV load in those patients was not higher than in the rest of
      patients, and the low EBV load prevented the development of lymphoproliferative
      disease. These results suggest that the presence of CD8(+) T lymphocytes in the
      bone marrow graft can control EBV load, thereby reducing the risk of developing
      lymphoproliferative disease.

PMID- 15478064
TI  - Time course and frequency of Epstein-Barr virus reactivation after kidney
      transplantation: linkage to renal allograft rejection.
AB  - The onset and frequency of Epstein-Barr virus (EBV) reactivation after kidney
      transplantation are unknown. By use of quantitative real-time polymerase chain
      reaction measurements, evidence of early EBV reactivation, occurring within the
      first week after the initiation of immunosuppressive therapy (median, 3 days),
      was observed in 13 of 23 patients, of whom 10 subsequently developed rejection
      episodes after 2-45 days (median, 5 days). By contrast, rejection was only
      diagnosed in 1 of 10 patients who did not show signs of viral reactivation. We
      suggest that EBV reactivation may induce a T cell response that, through the
      phenomenon of allo-cross-reactivity, could play a critical role in graft
      rejection.

PMID- 15478065
TI  - Persistent paradox of natural history of human T lymphotropic virus type I:
      parallel analyses of Japanese and Jamaican carriers.
AB  - Human T lymphotropic virus type I (HTLV-I) is endemic in southern Japan and the
      Caribbean, but the incidence of HTLV-I-associated diseases varies across
      geographic areas. We compared markers of disease pathogenesis among 51 age- and
      sex-matched HTLV-I carrier pairs from Japan and Jamaica. The mean antibody titer
      (P=.03) and detection of anti-Tax antibody (P=.002) were higher in Jamaican
      subjects than in Japanese subjects, but provirus load was similar between the 2
      groups (P=.26). The correlation between antibody titer and provirus load was more
      prominent among Jamaican subjects than among Japanese subjects (P=.06). These
      findings underscore the differences in host immune response to HTLV-I infection
      in 2 populations.

PMID- 15478066
TI  - Targeting virological core groups: a new paradigm for controlling herpes simplex
      virus type 2 epidemics.
AB  - BACKGROUND: Classic modeling of sexually transmitted diseases has focused on
      modeling behavioral heterogeneity and designing epidemic control strategies
      targeted at behavioral core groups. METHODS: We analyzed a new mathematical model
      of herpes simplex virus type 2 (HSV-2) epidemics that includes virological core
      groups (i.e., groups of individuals with high rates of viral reactivation) and
      suggest a new paradigm for epidemic control. We used our model, in conjunction
      with virological data, to determine the potential role of virological core groups
      in contributing to transmission and the effect that daily antiviral therapy (DAT)
      could have on reducing transmission if virological core groups were targeted.
      RESULTS: We estimated that a virological core group (11% of infected individuals)
      can cause a disproportionately large percentage (44%) of new infections and that
      a median of only 6.4 person-years of DAT would be necessary to prevent 1 HSV-2
      infection. We determined that relatively few individuals would need to receive
      DAT to substantially reduce the incidence of HSV-2 infection. CONCLUSION:
      Identifying and targeting individuals in the virological core group could be an
      effective and practical public health strategy for reducing transmission.
      Treating individuals who are high-frequency viral shedders should be evaluated as
      a strategy for reducing HSV-2 transmission.

PMID- 15478068
TI  - Influenza viruses resistant to the antiviral drug oseltamivir: transmission
      studies in ferrets.
AB  - Three type A influenza viruses, each of which has a distinct neuraminidase-gene
      mutation and is resistant to the neuraminidase inhibitor oseltamivir, have been
      isolated. Previously, in the ferret model, an R292K mutant of a type A (H3N2)
      virus was not transmitted under conditions in which the wild-type virus was
      transmitted. This model was used to investigate whether the E119V mutant of a
      type A (H3N2) virus and the H274Y mutant of a type A (H1N1) virus would be
      transmitted under similar circumstances. Both mutant viruses were transmitted,
      although the H274Y mutant required a 100-fold-higher dose for infection of donor
      ferrets and was transmitted more slowly than was the wild type. Both the mutant
      and the wild-type viruses retained their genotypic characteristics.

PMID- 15478067
TI  - Proinflammatory cytokines and chemokines in humans with Japanese encephalitis.
AB  - BACKGROUND: Japanese encephalitis virus (JEV), the mosquito-borne flavivirus,
      annually causes an estimated 35,000-50,000 encephalitis cases and 10,000-15,000
      deaths in Asia, and there is no antiviral treatment. The role played by the
      immune response in determining the outcome of human infection with JEV is poorly
      understood, although, in animal models of flavivirus encephalitis, unregulated
      proinflammatory cytokine responses can be detrimental. METHODS: We studied the
      innate, cellular, and humoral immune responses in 118 patients infected with JEV,
      of whom 13 (11%) died. RESULTS: Levels of interferon (IFN)- alpha , the
      proinflammatory cytokine interleukin (IL)-6, and the chemokine IL-8 were all
      higher in the cerebrospinal fluid (CSF) of the nonsurvivors than of the survivors
      (P=.04, P=.006, and P=.04, respectively), as were both the IL-6 : IL-4 ratio in
      CSF (a marker of the balance of pro- and anti-inflammatory cytokines) and the
      level of the chemokine RANTES (regulated on activation, normally T cell expressed
      and secreted) in plasma (P=.03). In contrast, levels of immunoglobulin (Ig) M and
      IgG in CSF and of IgM in plasma were higher in the survivors (P=.035, P=.003, and
      P=.009, respectively). Levels of IFN- gamma and nitric oxide did not vary with
      outcome. CONCLUSIONS: During JEV infection, elevated levels of proinflammatory
      cytokines and chemokines are associated with a poor outcome, but whether they are
      simply a correlate of severe disease or contribute to pathogenesis remains to be
      determined.

PMID- 15478069
TI  - Vitamin D receptor polymorphisms and susceptibility to tuberculosis in West
      Africa: a case-control and family study.
AB  - Vitamin D receptor (VDR) gene polymorphisms have been implicated in
      susceptibility to tuberculosis (TB), but reports have been inconsistent. We
      genotyped the VDR single-nucleotide polymorphisms (SNPs) FokI, BsmI, ApaI, and
      TaqI in 1139 case patients and control subjects and 382 families from The Gambia,
      Guinea, and Guinea-Bissau. The transmission-disequilibrium test on family data
      showed a significant global association of TB with SNP combinations FokI-BsmI
      ApaI-TaqI and FokI-ApaI that were driven by the increased transmission to
      affected offspring of the FokI F and ApaI A alleles in combination. The ApaI A
      allele was also transmitted to affected offspring significantly more often than
      expected. Case-control analysis showed no statistically significant association
      between TB and VDR variants. BsmI, ApaI, and TaqI showed strong linkage
      disequilibrium. The significance of the family-based associations found between
      TB and FokI-BsmI-ApaI-TaqI and the FA haplotype supports a role for VDR
      haplotypes, rather than individual genotypes, in susceptibility to TB.

PMID- 15478070
TI  - Selection of a moxifloxacin dose that suppresses drug resistance in Mycobacterium
      tuberculosis, by use of an in vitro pharmacodynamic infection model and
      mathematical modeling.
AB  - BACKGROUND: Moxifloxacin is a quinolone antimicrobial that has potent activity
      against Mycobacterium tuberculosis. To optimize moxifloxacin dose and dose
      regimen, pharmacodynamic antibiotic-exposure targets associated with maximal
      microbial kill and complete suppression of drug resistance in M. tuberculosis
      must be identified. METHODS: We used a novel in vitro pharmacodynamic infection
      model of tuberculosis in which we exposed M. tuberculosis to moxifloxacin with a
      pharmacokinetic half-life of decline similar to that encountered in humans. Data
      obtained from this model were mathematically modeled, and the drug-exposure
      breakpoint associated with the suppression of drug resistance was determined.
      Monte-Carlo simulations were performed to determine the probability that 10,000
      clinical patients taking different doses of moxifloxacin would achieve or exceed
      the drug-exposure breakpoint needed to suppress resistance to moxifloxacin in M.
      tuberculosis. RESULTS: The ratio of the moxifloxacin-free (non-protein-bound)
      area under the concentration-time curve from 0 to 24 h to the minimum inhibitory
      concentration associated with complete suppression of the drug-resistant mutant
      population was 53. For patients taking moxifloxacin doses of 400, 600, or 800
      mg/day, the calculated target-attainment rates to suppress drug resistance were
      59%, 86%, and 93%, respectively. CONCLUSION: A moxifloxacin dose of 800 mg/day is
      likely to achieve excellent M. tuberculosis microbial kill and to suppress drug
      resistance. However, tolerability of this higher dose is still unknown.

PMID- 15478071
TI  - Quinolone resistance is associated with increased risk of invasive illness or
      death during infection with Salmonella serotype Typhimurium.
AB  - In a registry-based cohort study, we determined the risk of invasive illness or
      death associated with infection with quinolone-resistant Salmonella serotype
      Typhimurium. We linked data from the Danish surveillance registry of enteric
      pathogens with data from the Danish civil registration system and 2 national
      health registries. Of 1323 patients infected with Salmonella Typhimurium, 46
      (3.5%) were hospitalized due an invasive illness within 90 days of infection, and
      16 (1.2%) died within 90 days of infection. After adjustment for age, sex, and
      comorbidity, infection with quinolone-resistant Salmonella Typhimurium was
      associated with a 3.15-fold (95% confidence interval, 1.39-7.10-fold) higher risk
      of invasive illness or death within 90 days of infection, compared with that
      observed for infection with pansusceptible strains.

PMID- 15478072
TI  - Chloroquine enhances survival in Bacillus anthracis intoxication.
AB  - The intentional release of anthrax in the United States in 2001 resulted in 11
      cases of inhalational disease, with an attendant mortality rate of 45%. Current
      therapeutic options for anthrax are limited; antimicrobials target only
      replicating organisms, thus allowing bacterial toxins to cause unchecked,
      devastating physiological derangements in the host. Novel approaches that target
      the cytotoxic effects of anthrax exotoxins are needed. Chloroquine (CQ), a
      commonly used antimalarial agent, endows anthrax-intoxicated murine peritoneal
      macrophages with a 50% and 35% marginal survival advantage at 2 and 4 h,
      respectively, over that of untreated control cells. The cell rescue is dose
      dependent and, at lower concentrations, results in delayed cell death. We
      subsequently studied the effect of CQ in BALB/c mice challenged with anthrax
      lethal toxin. CQ-treated mice demonstrated reduced tissue injury, as assessed by
      histopathological examination of the spleen and by peripheral blood differential
      cell count ratios. CQ significantly enhanced survival and may augment current
      treatment and prophylaxis options for this otherwise lethal infection.

PMID- 15478073
TI  - Tissue-specific contributions of pneumococcal virulence factors to pathogenesis.
AB  - We assessed the ability of Streptococcus pneumoniae mutants deficient in either
      choline binding protein A (CbpA), pneumolysin (Pln), pyruvate oxidase (SpxB),
      autolysin (LytA), pneumococcal surface protein A, or neuraminidase A (NanA) to
      replicate in distinct anatomical sites and translocate from one site to the next.
      Intranasal, intratracheal, and intravenous models of disease were assessed in 4
      week-old BALB/cJ mice by quantitation of bacterial titers in the relevant organs.
      Mice were also observed by use of real-time bioluminescent imaging (BLI). BLI
      allowed visualization of the bacteria in sites not tested by sampling. All
      mutants were created in D39 Xen7, a fully virulent derivative of capsular type 2
      strain D39 that contains an optimized luxABCDE cassette. NanA, SpxB, and, to a
      lesser extent, CbpA contributed to prolonged nasopharyngeal colonization, whereas
      CbpA and NanA contributed to the transition to the lower respiratory tract. Once
      lung infection was established, Pln, SpxB, and LytA contributed to bacterial
      replication in the lungs and translocation to the bloodstream. In the
      bloodstream, only Pln and LytA were required for high-titer replication, whereas
      CbpA was required for invasion of the cerebrospinal fluid. We conclude that
      transitions between body sites require virulence determinants distinct from those
      involved in organ-specific replication.

PMID- 15478074
TI  - Outcome of HIV-associated tuberculosis in the era of highly active antiretroviral
      therapy.
AB  - BACKGROUND: The benefit of highly active antiretroviral therapy (HAART) in the
      treatment of patients coinfected with tuberculosis (TB) and human
      immunodeficiency virus (HIV) is unclear because of concerns about treatment
      related complications. METHODS: We compared outcomes in patients starting TB
      treatment during the pre-HAART era (before 1996; n=36) with those in patients
      starting treatment during the HAART era (during or after 1996; n=60). RESULTS:
      During a median of 3.6 years of follow-up, 49 patients died or had an AIDS event.
      Compared with patients in the pre-HAART group, those in the HAART group had a
      lower risk of death (cumulative at 4 years, 43% vs. 22%; P=.012) and of death or
      having an AIDS event (69% vs. 43%; P=.023). Event risk within the first 2 months
      of TB treatment was exceptionally high in patients with CD4(+) cell counts <100
      cells/mm(3) and declined thereafter. HAART use during follow-up was associated
      with a marked reduction in event risk (adjusted hazard ratio, 0.38 [95%
      confidence interval, 0.16-0.91]). CONCLUSIONS: HAART substantially reduces new
      AIDS events and death in coinfected patients. Those with a CD4(+) cell count <100
      cells/mm(3) have a high event risk during the intensive phase of anti-TB
      treatment. These data should be taken into account when deciding to delay HAART
      in coinfected patients with CD4(+) cell counts <100 cells/mm(3).

PMID- 15478075
TI  - Does tuberculosis increase HIV load?
AB  - BACKGROUND: The effect that tuberculosis (TB) has on human immunodeficiency virus
      (HIV) disease progression is not clearly understood. METHODS: In an observational
      cohort study of HIV-infected adults in South Africa, baseline and final HIV load
      were compared between individuals who experienced an episode of TB (n=30) during
      follow-up and control subjects (n=56) matched by baseline CD4 cell count and
      follow-up time; linear regression modeling was used to control for confounding.
      RESULTS: Mean HIV load was higher in the TB group than in the non-TB control
      group for both baseline (4.73 vs. 4.24 log(10) copies/mL; P=.003) and final
      values (5.02 vs. 4.34 log(10) copies/mL; P<.001). After adjustment for baseline
      HIV load and World Health Organization HIV stage, the difference in final HIV
      load was 0.24 log(10) copies/mL (95% confidence interval, -0.01 to 0.50 log(10)
      copies/mL; P=.06). CONCLUSIONS: Poor prognosis for HIV-infected individuals after
      TB may be due to preexisting high HIV load rather than to the TB event itself. An
      episode of TB was associated with a small adjusted increase in HIV load at the
      end of the study--an increase that would not be regarded as clinically
      significant in an individual but could have some effect on HIV disease
      progression or HIV transmission at the population level. Prevention of TB is
      important for the reduction of HIV-related morbidity and mortality; however,
      antiretroviral therapy is required to have a major effect on survival in
      individuals with HIV disease.

PMID- 15478076
TI  - Anal intraepithelial neoplasia in heterosexual and homosexual HIV-positive men
      with access to antiretroviral therapy.
AB  - BACKGROUND: Studies of human immunodeficiency virus (HIV)-positive men have
      demonstrated high rates of anal intraepithelial neoplasia (AIN), a precursor to
      anal carcinoma, mostly in white homosexual men and men not receiving effective
      antiretroviral therapy (ART). METHODS: Ninety-two participants--53% Latino, 36%
      African American, and 40% without a history of receptive anal intercourse (RAI)-
      were evaluated with a behavioral questionnaire, liquid-based anal cytological
      testing, Hybrid Capture 2 human papillomavirus (HPV) DNA assay and polymerase
      chain reaction, and anal colposcopy with biopsy of lesions. RESULTS: High-risk
      HPV DNA was identified in 61%, and this was associated with a history of RAI (78%
      vs. 33%; P<.001); 47% had abnormal cytological results, and 40% had AIN on
      biopsy. In multivariate analysis, both were associated with a history of RAI
      (odds ratio [OR], 10 [P<.001] and OR, 3.6 [P=.02], respectively) and lower nadir
      CD4(+) cell counts (P=.06 and P=.01). Current ART use was protective (OR, 0.09;
      P<.01 and OR, 0.18; P=.02). CONCLUSIONS: Although anal infections with high-risk
      HPV and AIN in HIV-positive men are associated with a history of RAI, both
      conditions are commonly identified in HIV-positive men without this history. Both
      lower nadir CD4(+) cell counts and lack of current ART were associated with AIN
      but not with the detection of anal HPV.

PMID- 15478077
TI  - Correlation between interferon- gamma secretion and cytotoxicity, in virus
      specific memory T cells.
AB  - ELISpot and intracellular cytokine staining are replacing the traditional
      cytolytic ((51)Cr release) assay method in vaccine trials using human
      immunodeficiency virus (HIV)-1, and it is widely assumed that the number of
      interferon (IFN)- gamma -secreting T cells is a surrogate for the level of
      cytolytic activity. Thus, we sought to determine whether the detection of IFN-
      gamma in CD8(+) T cells correlates with cytolytic ability in vitro. In 29 (69.0%)
      of 42 HIV-1-seronegative immunocompetent individuals (22 unvaccinated and 20
      vaccinated), virus-specific T cell responses recognizing cytomegalovirus, Epstein
      Barr virus, and influenza and HIV-1 Gag epitopes were detected by at least 1
      assay method (ELISpot, intracellular cytokine staining, and/or (51)Cr release),
      and 18 (62.1%) of these 29 demonstrated both IFN- gamma secretion and cytolysis.
      There was strong correlation between the results of IFN- gamma ELISpot and those
      of IFN- gamma intracellular cytokine staining ( rho =0.88) and between the
      results of (51)Cr release and those of intracellular cytokine staining ( rho
      =0.81); although the correlation is not absolute, intracellular cytokine staining
      can be used--and is superior to ELISpot--as a surrogate for cytolytic assays.

PMID- 15478079
TI  - Natural course of severe acute respiratory syndrome-associated coronavirus
      immunoglobulin after infection.

PMID- 15478078
TI  - Abrogation of attenuated lentivirus-induced protection in rhesus macaques by
      administration of depo-provera before intravaginal challenge with simian
      immunodeficiency virus mac239.
AB  - In nonhuman primate models of acquired immunodeficiency syndrome, live attenuated
      lentiviruses provide the most reliable protection from systemic and mucosal
      challenge with pathogenic simian immunodeficiency virus (SIV). Although live
      attenuated lentiviruses may never be used in humans because of safety concerns,
      understanding the nature of the protective immune mechanisms induced by live
      attenuated vaccines in primate models will be useful for developing other vaccine
      approaches. Approximately 60% of rhesus macaques immunized with nonpathogenic
      simian-human immunodeficiency virus (SHIV) strain 89.6 are protected from
      infection or clinical disease after intravaginal (IVAG) challenge with pathogenic
      SIVmac239. The goal of the present study was to determine whether administration
      of Depo-Provera before IVAG challenge with SIV decreases the protective efficacy
      of infection with SHIV89.6. The rate of protection after IVAG challenge with
      SIVmac239 was significantly lower (P<.05), and the acute postchallenge plasma
      viral RNA levels were significantly higher (P<.006), in Depo-Provera-treated,
      SHIV89.6-immunized macaques than in Depo-Provera-naive, SHIV89.6-immunized
      macaques. In the primate model of sexual transmission of human immunodeficiency
      virus, treatment with progesterone before IVAG challenge with a pathogenic virus
      can decrease the efficacy of a model "vaccine."

PMID- 15478081
TI  - The discovery of hantaan virus: comparative biology and serendipity in a world at
      war.

PMID- 15478083
TI  - Components of variance underlying fitness in a natural population of the great
      tit Parus major.
AB  - Traits that are closely associated with fitness tend to have lower heritabilities
      (h2) than those that are not. This has been interpreted as evidence that natural
      selection tends to deplete genetic variation more rapidly for traits more closely
      associated with fitness (a corollary of Fisher's fundamental theorem), but Price
      and Schluter (1991) suggested the pattern might be due to higher residual
      variance in traits more closely related to fitness. The relationship between 10
      different traits for females, seven traits for males, and overall fitness
      (lifetime recruitment) was quantified for great tits (Parus major) studied in
      their natural environment of Wytham Wood, England, using data collected over 39
      years. Heritabilities and the coefficients of additive genetic and residual
      variance (CVA and CVR, respectively) were estimated using an "animal model." For
      both males and females, a trait's correlation (r) with fitness was negatively
      related to its h2 but positively related to its CVR. The CVA was not related to
      the trait's correlation with fitness in either sex. This is the third study using
      directly measured fitness in a wild population to show the important role of
      residual variation in determining the pattern of lower heritabilities for traits
      more closely related to fitness.

PMID- 15478084
TI  - Effects of brood manipulation costs on optimal sex allocation in social
      hymenoptera.
AB  - In eusocial Hymenoptera, queens and workers are in conflict over optimal sex
      allocation. Sex ratio theory, while generating predictions on the extent of this
      conflict under a wide range of conditions, has largely neglected the fact that
      worker control of investment almost certainly requires the manipulation of brood
      sex ratio. This manipulation is likely to incur costs, for example, if workers
      eliminate male larvae or rear more females as sexuals rather than workers. In
      this article, we present a model of sex ratio evolution under worker control that
      incorporates costs of brood manipulation. We assume cost to be a continuous,
      increasing function of the magnitude of sex ratio manipulation. We demonstrate
      that costs counterselect sex ratio biasing, which leads to less female-biased
      population sex ratios than expected on the basis of relatedness asymmetry.
      Furthermore, differently shaped cost functions lead to different equilibria of
      manipulation at the colony level. While linear and accelerating cost functions
      generate monomorphic equilibria, decelerating costs lead to a process of
      evolutionary branching and hence split sex ratios.

PMID- 15478085
TI  - Porcupine feeding scars and climatic data show ecosystem effects of the solar
      cycle.
AB  - Using North American porcupine (Erethizon dorsatum) feeding scars on trees as an
      index of past porcupine abundance, we have found that porcupine populations have
      fluctuated regularly over the past 130 years in the Bas St. Laurent region of
      eastern Quebec, with superimposed periodicities of 11 and 22 years. Coherency and
      phase analyses showed that this porcupine population cycle has closely followed
      the 11- and 22-year solar activity cycles. Fluctuations in local precipitation
      and temperature were also cyclic and closely related to both the solar cycle and
      the porcupine cycle. Our results suggest that the solar cycle indirectly sets the
      rhythm of population fluctuations of the most abundant vertebrate herbivore in
      the ecosystem we studied. We hypothesize that the solar cycle has sufficiently
      important effects on the climate along the southern shore of the St. Lawrence
      estuary to locally influence terrestrial ecosystem functioning. This constitutes
      strong evidence for the possibility of a causal link between solar variability
      and terrestrial ecology at the decadal timescale and local spatial scale, which
      confirms results obtained at greater temporal and spatial scales.

PMID- 15478086
TI  - Density-dependent sexual selection in external fertilizers: variances in male and
      female fertilization success along the continuum from sperm limitation to sexual
      conflict in the sea urchin Strongylocentrotus franciscanus.
AB  - Sperm competition and female choice are fundamentally driven by gender
      differences in investment per offspring and are often manifested as differences
      in variance in reproductive success: males compete and have high variance; most
      females are mated and have low variance. In marine organisms that broadcast
      spawn, however, females may encounter either sperm limitation or sperm
      competition. I measured the fertilization success of male and female
      Strongylocentrotus franciscanus over a range of population densities using
      microsatellite markers. Female fertilization success first increased and then
      decreased with mate density, limited at low density by sperm limitation and at
      high density by polyspermy. Mate density affected variance in fertilization
      success in both males and females. In males, the variance in fertilization
      success increased with mate density. In females, the pattern was more complex.
      The variance in female success increased similarly to males with increased mate
      density but then decreased to low levels at intermediate densities, where almost
      all eggs were fertilized. As density increased further, the female variances
      again increased as polyspermy lowered average fertilization success. Male and
      female variances differed only at intermediate densities. At low densities, both
      sexes may be under selection to increase fertilization success; at intermediate
      densities, males may compete; and at high densities, both sexes may be under
      selection to increase success by increasing (males) or decreasing (females)
      likelihood of fertilization during sexual conflict. Only within a narrow range of
      densities do patterns of sexual selection mirror those typically noted in
      internally fertilizing taxa.

PMID- 15478087
TI  - Mechanisms of coexistence in competitive metacommunities.
AB  - Although there is a large body of theory on spatial competitive coexistence, very
      little of it involves comparative analyses of alternative mechanisms. We thus
      have limited knowledge of the conditions under which multiple spatial mechanisms
      can operate or of emergent properties arising from interactions between
      mechanisms. Here we present a mathematical framework that allows for comparative
      analysis of spatial coexistence mechanisms. The basis for comparison is
      mechanisms operating in spatially homogeneous competitive environments (e.g.,
      life-history trade-offs) versus mechanisms operating in spatially heterogeneous
      competitive environments (e.g., source-sink dynamics). Our comparative approach
      leads to several new insights about spatial coexistence. First, we show that
      spatial variation in the expression of a life-history trade-off leads to a unique
      regional pattern that cannot be predicted by considering trade-offs or source
      sink dynamics alone. This result represents an instance where spatial
      heterogeneity constrains rather than promotes coexistence, and it illustrates the
      kind of counterintuitive emergent properties that arise due to interactions
      between different classes of mechanisms. Second, we clarify the role of dispersal
      mortality in spatial coexistence. Previous studies have shown that coexistence
      can be constrained or facilitated by dispersal mortality. Our broader analysis
      distinguishes situations where dispersal mortality is not necessary for
      coexistence from those where such mortality is essential for coexistence because
      it preserves spatial variation in the strength of competition. These results form
      the basis for two important future directions: evolution of life-history traits
      in spatially heterogeneous environments and elucidation of the cause and effect
      relationship(s) between biodiversity and ecosystem functioning.

PMID- 15478088
TI  - Testosterone in tropical birds: effects of environmental and social factors.
AB  - Previous investigations suggest that male tropical birds have lower plasma
      testosterone concentrations than northern latitude species. To test whether this
      generalization is valid, we analyzed all currently available plasma testosterone
      data of tropical birds. We focused on peak breeding testosterone levels using
      phylogenetic and conventional statistics. Explanatory variables considered were
      social mating system, type of territoriality, breeding season length, and
      altitude. On average, tropical birds had lower mean peak testosterone levels than
      northern temperate birds. However, in several tropical species, testosterone
      levels were well within the range of northern latitude birds. Without controlling
      for phylogeny, breeding season length, type of territoriality, and altitude
      explained a significant proportion of the variance in testosterone levels. The
      shorter the breeding season, the higher the testosterone levels. Tropical birds
      that defend a breeding season territory had higher testosterone levels than birds
      that were year-round territorial or colonial, and testosterone levels were
      positively correlated with altitude. When controlling for phylogeny, only
      breeding season length predicted testosterone levels. In conclusion, we propose
      to refine previous notions of low plasma testosterone levels in tropical birds:
      short breeding seasons and perhaps environmental conditions at high altitudes
      precipitate conditions under which high testosterone levels are beneficial in the
      tropics.

PMID- 15478089
TI  - Shared and unique features of evolutionary diversification.
AB  - A fundamental question in evolutionary biology asks whether organisms
      experiencing similar selective pressures will evolve similar solutions or whether
      historical contingencies dominate the evolutionary process and yield disparate
      evolutionary outcomes. It is perhaps most likely that both shared selective
      forces as well as unique histories play key roles in the course of evolution.
      Consequently, when multiple species face a common environmental gradient, their
      patterns of divergence might exhibit both shared and unique elements. Here we
      describe a general framework for investigating and evaluating the relative
      importance of these contrasting features of diversification. We examined
      morphological diversification in three species of livebearing fishes across a
      predation gradient. All species (Gambusia affinis from the United States of
      America, Brachyrhaphis rhabdophora from Costa Rica, and Poecilia reticulata from
      Trinidad) exhibited more elongate bodies, a larger caudal peduncle, and a
      relatively lower position of the eye in predator populations. This shared
      response suggests that common selective pressures generated parallel outcomes
      within three different species. However, each species also exhibited unique
      features of divergence, which might reflect phylogenetic tendencies, chance
      events, or localized environmental differences. In this system, we found that
      shared aspects of divergence were of larger magnitude than unique elements,
      suggesting common natural selective forces have played a greater role than unique
      histories in producing the observed patterns of morphological diversification.
      Assessing the nature and relative importance of shared and unique responses
      should aid in elucidating the relative generality or peculiarity in evolutionary
      divergence.

PMID- 15478090
TI  - Effects of temporal variability on rare plant persistence in annual systems.
AB  - Traditional conservation biology regards environmental fluctuations as
      detrimental to persistence, reducing long-term average growth rates and
      increasing the probability of extinction. By contrast, coexistence models from
      community ecology suggest that for species with dormancy, environmental
      fluctuations may be essential for persistence in competitive communities. We used
      models based on California grasslands to examine the influence of interannual
      fluctuations in the environment on the persistence of rare forbs competing with
      exotic grasses. Despite grasses and forbs independently possessing high fecundity
      in the same types of years, interspecific differences in germination biology and
      dormancy caused the rare forb to benefit from variation in the environment. Owing
      to the buildup of grass competitors, consecutive favorable years proved highly
      detrimental to forb persistence. Consequently, negative temporal autocorrelation,
      a low probability of a favorable year, and high variation in year quality all
      benefited the forb. In addition, the litter produced by grasses in a previously
      favorable year benefited forb persistence by inhibiting its germination into
      highly competitive grass environments. We conclude that contrary to conventional
      predictions of conservation and population biology, yearly fluctuations in
      climate may be essential for the persistence of rare species in invaded habitats.

PMID- 15478091
TI  - From individual behavior to metapopulation dynamics: unifying the patchy
      population and classic metapopulation models.
AB  - Spatially structured populations in patchy habitats show much variation in
      migration rate, from patchy populations in which individuals move repeatedly
      among habitat patches to classic metapopulations with infrequent migration among
      discrete populations. To establish a common framework for population dynamics in
      patchy habitats, we describe an individual-based model (IBM) involving a
      diffusion approximation of correlated random walk of individual movements. As an
      example, we apply the model to the Glanville fritillary butterfly (Melitaea
      cinxia) inhabiting a highly fragmented landscape. We derive stochastic patch
      occupancy model (SPOM) approximations for the IBMs assuming pure demographic
      stochasticity, uncorrelated environmental stochasticity, or completely correlated
      environmental stochasticity in local dynamics. Using realistic parameter values
      for the Glanville fritillary, we show that the SPOMs mimic the behavior of the
      IBMs well. The SPOMs derived from IBMs have parameters that relate directly to
      the life history and behavior of individuals, which is an advantage for model
      interpretation and parameter estimation. The modeling approach that we describe
      here provides a unified framework for patchy populations with much movements
      among habitat patches and classic metapopulations with infrequent movements.

PMID- 15478092
TI  - Changes in dispersal during species' range expansions.
AB  - Explanations for rapid species' range expansions have typically been purely
      ecological, with little attention given to evolutionary processes. We tested
      predictions for the evolution of dispersal during range expansion using four
      species of wing-dimorphic bush cricket (Conocephalus discolor, Conocephalus
      dorsalis, Metrioptera roeselii, and Metrioptera brachyptera). We observed
      distinct changes in dispersal in the two species with expanding ranges. Recently
      colonized populations at the range margin showed increased frequencies of
      dispersive, long-winged (macropterous) individuals, compared with longer
      established populations in the range core. This increase in dispersal appeared to
      be short-lived because 5-10 years after colonization populations showed similar
      incidences of macroptery to populations in the range core. These changes are
      consistent with evolutionary change; field patterns persisted when nymphs were
      reared under controlled environmental conditions, and range margin individuals
      reared in the laboratory flew farther than range core individuals in a wind
      tunnel. There was also a reproductive trade-off with dispersal in both females
      and males, which could explain the rapid reversion to lower rates of dispersal
      once populations become established. The effect of population density on wing
      morphology differed between populations from the range core (no significant
      effect of density) and expanding range margins (negative density dependence),
      which we propose is part of the mechanism of the changes in dispersal. Transient
      changes in dispersal are likely to be common in many species undergoing range
      expansion and can have major population and biogeographic consequences.

PMID- 15478093
TI  - Testing species boundaries in an ancient species complex with deep
      phylogeographic history: genus Xantusia (Squamata: Xantusiidae).
AB  - Identification of species in natural populations has recently received increased
      attention with a number of investigators proposing rigorous methods for species
      delimitation. Morphologically conservative species (or species complexes) with
      deep phylogenetic histories (and limited gene flow) are likely to pose particular
      problems when attempting to delimit species, yet this is crucial to comparative
      studies of the geography of speciation. We apply two methods of species
      delimitation to an ancient group of lizards (genus Xantusia) that occur
      throughout southwestern North America. Mitochondrial cytochrome b and
      nicotinamide adenine dinucleotide dehydrogenase subunit 4 gene sequences were
      generated from samples taken throughout the geographic range of Xantusia. Maximum
      likelihood, Bayesian, and nested cladogram analyses were used to estimate
      relationships among haplotypes and to infer evolutionary processes. We found
      multiple well-supported independent lineages within Xantusia, for which there is
      considerable discordance with the currently recognized taxonomy. High levels of
      sequence divergence (21.3%) suggest that the pattern in Xantusia may predate the
      vicariant events usually hypothesized for the fauna of the Baja California
      peninsula, and the existence of deeply divergent clades (18.8%-26.9%) elsewhere
      in the complex indicates the occurrence of ancient sundering events whose genetic
      signatures were not erased by the late Wisconsin vegetation changes. We present a
      revised taxonomic arrangement for this genus consistent with the distinct mtDNA
      lineages and discuss the phylogeographic history of this genus as a model system
      for studies of speciation in North American deserts.

PMID- 15478094
TI  - Quantitative tests of general models for the evolution of development.
AB  - Comparative developmental biologists have proposed models to describe patterns of
      conserved features in vertebrate ontogeny. The hourglass model suggests
      evolutionary change is most difficult at an intermediate "phylotypic" stage, the
      adaptive penetrance model suggests change is easiest at an intermediate stage,
      and the early conservation model suggests change is easier later in ontogeny.
      Although versions of some of these models have been discussed since the
      nineteenth century, quantitative approaches have been proposed only recently.
      Here we present quantitative phylogenetic approaches to evaluating trends in the
      evolution of ontogeny. We apply these approaches to the proposed models and
      demonstrate that an existing approach to assessing these models is biased. We
      show that the hourglass, adaptive penetrance, and early conservation models are
      unnecessarily complex explanations of the patterns observed in developmental
      event data for 14 species of vertebrates. Rather, a simpler model that postulates
      that evolutionary change is easier between ontogenetically adjacent events is
      adequate.

PMID- 15478095
TI  - Disentangling food quality from resistance against parasitoids: diet choice by a
      generalist caterpillar.
AB  - The relative importance of food quality and enemy-reduced space is a central but
      unresolved issue in the evolutionary ecology of host use by phytophagous insects.
      Indeed, a practical obstacle to experimentally disentangling the functional roles
      of these factors is the host specificity of insect herbivores, particularly toxic
      plant specialists. In this study, we employ a toxic plant generalist to uniquely
      disentangle these alternative explanations. We experimentally demonstrate that
      the value of enemy-reduced space supersedes that of food quality in determining
      the diet and host preference of the polyphagous woolly bear caterpillar Grammia
      geneura (Lepidoptera: Arctiidae). Caterpillars sacrificed superior growth
      efficiency in choosing a mixed diet that included toxic host plants and provided
      resistance against parasitoids. The resistance of individual caterpillars was
      associated with the relative amount of defensive plants eaten as well as with the
      sequestration of pyrrolizidine alkaloids from one such plant (Senecio
      longilobus).

PMID- 15478098
TI  - Carotid intima-media thickness better differentiates between groups of stroke
      patients and persons without cerebrovascular disease than other conventional and
      novel risk factors.
AB  - When measured by ultrasound, the morphological markers of carotid atherosclerosis
      such as intima-media thickness (IMT) and cross-sectional plaque area have been
      associated with the risk of ischaemic stroke. We set out to determine whether the
      morphological parameters of the carotid arteries made it possible to better
      differentiate between groups of older atherothrombotic stroke patients and
      persons without cerebrovascular disease than conventional and novel risk factors
      of stroke. Of the total number of 623 persons examined, 54 stroke patients (mean
      age 63.3 years) and 74 controls without cerebrovascular disease (mean age 66.3
      years) fulfilled the inclusion criteria for this investigation and were enrolled
      in the case-control study. After adjustment for age, gender and education level,
      the strongest associations were found between stroke and carotid IMT [odds ratio
      (OR) = 10.6; 95% confidence interval (CI): 4.3-26.9] and plaque area (OR = 5.4;
      95%CI: 2.3-13.1). Other risk factors showed weaker associations with stroke
      occurrence. Of the clinical risk factors, a significant association was found
      between stroke and coronary heart disease (OR = 3.5; 95%CI: 1.2-10.2),
      hypertension (OR = 3.2; 95%CI: 1.5-7.2) and smoking (OR = 2.7; 95%CI: 1.1-6.4).
      From the laboratory-derived risk factors a significant association was found
      between stroke and triglyceride levels (OR = 4.4; 95%CI: 1.9-10.0), and an
      inverse correlation was observed between stroke occurrence and HDL-cholesterol
      level (OR = 0.4; 95%CI: 0.2-0.8). The carotid IMT and plaque area, measured with
      the use of ultrasonography, showed a better correlation with stroke occurrence
      than currently recognised clinical and biochemical risk factors. The intima-media
      thickness and plaque area of the carotid arteries could be useful parameters in
      the development of strategies to identify patients at high risk of
      atherothrombotic ischaemic stroke.

PMID- 15478097
TI  - A genomewide search using an original pairwise sampling approach for large
      genealogies identifies a new locus for total and low-density lipoprotein
      cholesterol in two genetically differentiated isolates of Sardinia.
AB  - A powerful approach to mapping the genes for complex traits is to study isolated
      founder populations, in which genetic heterogeneity and environmental noise are
      likely to be reduced and in which extended genealogical data are often available.
      Using graph theory, we applied an approach that involved sampling from the large
      number of pairwise relationships present in an extended genealogy to reconstruct
      sets of subpedigrees that maximize the useful information for linkage mapping
      while minimizing calculation burden. We investigated, through simulation, the
      properties of the different sets in terms of bias in identity-by-descent (IBD)
      estimation and power decrease under various genetic models. We applied this
      approach to a small isolated population from Sardinia, the village of Talana,
      consisting of a unique large and complex pedigree, and performed a genomewide
      search through variance-components linkage analysis for serum lipid levels. We
      identified a region of significant linkage on chromosome 2 for total serum
      cholesterol and low-density lipoprotein (LDL) cholesterol. Through higher-density
      mapping, we obtained an increased linkage for both traits on 2q21.2-q24.1, with a
      LOD score of 4.3 for total serum cholesterol and of 3.9 for LDL cholesterol. A
      replication study was performed in an independent and larger set from a
      genetically differentiated isolated population of the same region of Sardinia,
      the village of Perdasdefogu. We obtained consistent linkage to the region for
      total serum cholesterol (LOD score 1.4) and LDL cholesterol (LOD score 2.2), with
      a level of concordance uncommon for complex traits, and refined the location of
      the quantitative-trait locus. Interestingly, the 2q21.1-22 region has also been
      linked to premature coronary heart disease in Finns, and, in the adjacent 2q14
      region, significant linkage with triglycerides has been reported in Hutterites.

PMID- 15478099
TI  - 4-OH-TEMPO prevents the morphological alteration of rat thymocytes primed to
      apoptosis by oxidative stress inducer ButOOH.
AB  - Thymocytes exposed to the pro-oxidant tert-butyl-hydroperoxide (ButOOH) display a
      number of dramatic changes in morphology similar to those observed in the case of
      dexamethasone-treated cells. Both reagents induce nuclear chromatin peripheral
      aggregation below the nuclear membrane. Some nuclei themselves break up producing
      two or more fragments. ButOOH-treated cells are morphologically characterised by
      cell shrinkage, extensive surface blebbing and, finally, fragmentation into
      membrane-bound apoptotic bodies composed of cytoplasm and tightly packed with or
      without nuclear fragments. An increased level of lipid hydroxyperoxides was
      detected after exposure of thymocytes to ButOOH. Both oxidative stress markers
      and morphological damage to cells were prevented by the antioxidant 4-OH-TEMPO.

PMID- 15478096
TI  - Complex genetics of amyotrophic lateral sclerosis.

PMID- 15478100
TI  - Anatomical and histological data on the ciliary ganglion in the Egyptian spiny
      mouse (Acomys cahirinus Desmarest).
AB  - The morphology and topography of the ciliary ganglion in the Egyptian spiny mouse
      were studied with use of histochemical and histological techniques. The ciliary
      ganglion of the Egyptian spiny mouse consisted of between 3 and 4 agglomerations
      of nerve cells. The largest was situated at the point where the ventral branch of
      the oculomotor nerve divides into two branches. The next two smaller aggregations
      were located on the superior and lateral surfaces of the optic nerve where it
      crossed the oculomotor nerve. From the main agglomerations of neurocytes arose
      between 3 and 4 intensively stained postganglionic cholinergic fibres. These
      followed the optic nerve to the eyeball. On the cross-sections of these bundles
      small agglomerations of neurocytes were observed. These decreased in size to only
      2 or 3 cells towards the sclera. The ganglionic neurocytes in the largest
      ganglion varied from 15 to 30 microm in diameter. They were distributed uniformly
      over the whole surface of the sections. All the ganglia had connective capsules.

PMID- 15478101
TI  - The development of the epidural space in human embryos.
AB  - The epidural space is seen in embryos at stage 17 (41 days) on the periphery of
      the primary meninx. During stage 18 (44 days) the dura mater proper appears and
      the epidural space is located between this meninx and the perichondrium and
      contains blood vessels. During the last week of the embryonic period (stages 20
      23) the epidural space is evident around the circumference of the spinal cord. On
      the posterior surface it is found between the dura mater and the mesoderm of the
      dorsal body wall.

PMID- 15478103
TI  - Developmental expression of SNAP-25 protein in the rat striatum and cerebral
      cortex.
AB  - The developmental changes of 25-kDa synaptosomal-associated protein (SNAP-25)
      expression in the rat striatum and cerebral cortex were examined using Western-
      blotting and densitometric scanning of immunoblots. Analysis of the striatum
      extracts from postnatal day 0 (P0) to postnatal day 120 (P120) demonstrated that
      SNAP-25 is poorly expressed until P14. From this point the expression level
      gradually increases to reach a maximum on P60 and then decreases. The pattern of
      SNAP-25 expression in the rat cerebral cortex is different. Two peaks are
      observed, the first on P10 and the second on P60, after which the expression
      level decreases. These results appear to confirm the role of SNAP-25 protein in
      axon outgrowth and synaptogenesis in the nervous system.

PMID- 15478102
TI  - The pancreaticoduodenal arteries in human foetal development.
AB  - Knowledge of the course of the pancreaticoduodenal arteries is of great
      importance in pancreatic surgery. Lack of care in the preparation of these
      vessels may lead to ischaemia or necrosis of the duodenum, the first loop of the
      jejunum, the head of the pancreas and even the liver, bile ducts and transverse
      colon. In such events, the surgeon would need to diagnose the course of the
      vessels and their anastomoses intraoperatively. Anatomical dissection in this
      special area diminishes the risk of early complications in the form of bleeding
      and late complications in the form of narrowing of the anastomoses, fistulas,
      necrosis and intestinal ileus after surgical resection or drainage. The aim of
      the present study was to determine the variability of the pancreaticoduodenal
      arteries in human foetuses. The material examined consisted of 60 human foetuses
      of both sexes (33 male, 27 female) from spontaneous abortion or stillbirth and
      ranging in age from the 16th to 38th week of prenatal life. White latex solution
      to of volume between 15 ml and 30 ml was injected into the thoracic aorta. The
      results of this were that a typical pancreatic supply from the coeliac trunk and
      superior mesenteric artery was observed in all cases. The coeliac trunk, splenic
      artery and gastroduodenal artery also appeared invariably. However, variability
      was observed in further generations of branches. The gastroduodenal artery with
      its branches, the anterior and posterior pancreaticoduodenal arteries, was
      constantly present. Irrespective of the sex of the foetus, in 10% of cases a
      large vessel was observed which ran horizontally on the anterior surface of the
      pancreas from head to tail and which originated in the anterior superior
      pancreaticoduodenal artery. We termed this vessel the "anterior pancreatic
      artery". In all cases there were anterior and posterior pancreaticoduodenal
      arcades, but in two cases (3.3%) a double anterior pancreaticoduodenal arcade was
      observed.

PMID- 15478104
TI  - Development of the myelin sheath of the hypogastric nerves in a human foetus aged
      23 weeks.
AB  - The formation of the myelin sheath of the human hypogastric nerves was studied by
      electron microscopy in a foetus of 23 weeks of postovulatory age (220 mm C-R
      length). In the investigated foetus the hypogastric nerves were mainly composed
      of bundles of unmyelinated fibres. The myelinated fibres were seen to be at
      different stages of myelination. Well myelinated fibres had thick compact
      laminated myelin. The number of myelin lamellae on a single fibre was 22.

PMID- 15478105
TI  - Venous drainage of the middle lobe of the right lung in man.
AB  - The shape of the middle lobe of the right lung may vary greatly because of the
      varying extent of its surfaces in different specimens and the profuse branching
      of the two segmental bronchi, arteries and veins. The architecture of the middle
      lobe is therefore especially difficult to understand. For these reasons,
      attention must be paid to the arrangements of the veins which separate its
      segments. Thus, the aim of this study was to investigate the ways in which venous
      drainage of the middle lobe segments may take place. The studies were performed
      on 40 organs taken from adult human cadavers of both sexes. The pulmonary vessels
      and bronchi were filled with Plastogen G, after which corrosion casts were made
      and skeletonised. The lateral segment (SIV) and the medial segment (SV) of the
      middle lobe were drained in 55% of specimens by one vein and in 35% of specimens
      by two separately terminated veins. Considerably less frequently there were 3
      veins (7.5% of specimens) and only in 2.5% of specimens--4 veins. In specimens
      where the middle lobe was drained by one vein (55%) it was formed by joining the
      lateral (V4) and the medial (V5) segmental veins. In 32.5% of specimens these two
      segmental veins were formed by a junction of their typical sub-segmental
      tributaries, where the posterior sub-segmental vein V4a and the superior sub
      segmental vein V5a were intra-segmental veins, whereas the anterior sub-segmental
      vein V4b and the inferior sub-segmental vein V5b were inter-segmental veins. In
      the remaining 22.5% of specimens with one vein of the middle lobe we noticed
      modifications in the course of the bronchi, arteries and veins. In the middle
      lobes drained by two separate veins (35% of specimens) there were independently
      running segmental veins, V4 and V5. These were formed by their typical
      tributaries (15%), whereas in the remaining 20% of specimens there were unusual
      patterns. Three individual veins of the middle lobe (7.5% of specimens)
      accompanied the lateral-medial type of bronchial arrangement in 5% of specimens,
      while in 2.5% of specimens the bronchial pattern was of the superior-inferior
      type. These veins run so as to form more often two superior and one inferior
      vein. The venous pattern of the middle lobe was consistent with the bronchial and
      arterial patterns in 35% of specimens. However, this conformation was present in
      those organs (32.5% of specimens) where the middle lobe was drained by one vein
      and only in 2.5% of specimens if there were two veins. If 3 or 4 individually
      emptied veins were present, we could not find any organ in which the bronchial,
      arterial and venous pattern would be fully compatible. Thus, the research
      revealed that convenient conditions for the separation of the segments of the
      middle lobe of the right lung were present in approximately 1/3 of the middle
      lobes.

PMID- 15478106
TI  - The topographical anatomy of the round window and related structures for the
      purpose of cochlear implant surgery.
AB  - The treatment of total deafness using a cochlear implant has now become a routine
      medical procedure. The tendency to expand the audiological indications for
      cochlear stimulation and to preserve the remnants of hearing has brought new
      problems. The authors have studied the topographical anatomy of the internal
      structures of the ear in the area where cochleostomy is usually performed and an
      implant electrode inserted. Ten human temporal bones were obtained from cadavers
      and prepared in a formalin stain. After dissection of the bone in the area of
      round and oval windows, the following diameters were measured using a microscope
      with a scale: the transverse diameters of the cochlear and vestibular scalae at
      the level of the centre of the round window and 0.5 mm anteriorly to the round
      window, the distance between the windows and the distances from the end of the
      spiral lamina to the centre of the round window and to its anterior margin. The
      width of the cochlear scala at the level of the round window was 1.23 mm, and 0.5
      mm anteriorly to the round window membrane it was 1.24 mm. The corresponding
      diameters for the vestibular scala are 1.34 and 1.27 mm. The distances from the
      end of the spiral lamina to the centre of the round window and to its anterior
      margin are 1.26 and 2.06 respectively. The authors noted that the two methods of
      electrode insertion show a difference of 2 mm in the length of the stimulated
      spiral lamina. The average total length of the unstimulated lamina is 2.06 and
      4.06 in the two situations respectively.

PMID- 15478107
TI  - Anatomical variations of the median nerve distribution and communication in the
      arm.
AB  - Anatomical variations of peripheral nerves constitute a potentially important
      clinical and surgical issue. The aim of this work is to study the variations of
      the median nerve in the arm with respect to its branching pattern and
      distribution as well as its possible communication with the musculocutaneous
      and/or ulnar nerves. Sixty arms pertaining to 30 preserved human cadavers,
      ranging in age from 30 to 67 years, were dissected in pursuit of this aim. In one
      limb out of 60 (1.7%) the median nerve gave off muscular branches to the
      brachialis muscle as well as a branch from its lateral root to supply both heads
      of the biceps brachii muscle. Concomitantly the musculocutaneous nerve was
      absent. The same limb demonstrated a branch from the lateral cord of the brachial
      plexus supplying the coracobrachialis muscle. Three limbs (5%) showed a
      communicating branch between the median and the musculocutaneous nerves. These
      observations should be considered when a high median nerve paralysis is shown to
      originate in the axilla or proximal arm in a patient presenting with weakness of
      forearm flexion and supination. Similarly, it can explain weakness of the arm
      flexor muscles in thoracic outlet syndrome with median nerve affection.

PMID- 15478108
TI  - Notes on the morphology of the tricuspid valve in the adult human heart.
AB  - Rapid progress in the field of interventional cardiology has caused research in
      the field of morphometry of the heart to be in constant demand. In this study,
      performed on a group of 75 adult human hearts, the authors have attempted to
      assess the form and number of the main and accessory cusps in the tricuspid
      valve. We have classified particular forms into 8 groups, depending on the number
      of cusps and we have divided the cusps into 3 main groups, depending on the
      support of the chordae tendineae.

PMID- 15478109
TI  - The spinal trigeminal nucleus--considerations on the structure of the nucleus
      caudalis.
AB  - The caudal part (nucleus caudalis) of the spinal trigeminal nucleus is considered
      to be the site of the second order neurons of the nociceptive pathways of the
      face. Recent studies have supported the co-participation in these circuits of the
      oral part of the same nucleus (nucleus oralis). The aims of the present study
      are: 1) to determine the morphology of the nucleus caudalis in human preparates;
      2) to consider whether there is any structural basis for the pathways of signal
      transmission observed in animal experiments; 3) to provide evidence-based support
      for further consideration on the orofacial pathways. The studies were made using
      the Bielschowsky silver staining technique (on blocks) applied to drawn pieces of
      brainstems from human cadavers. On the sections the outer laminae of the nucleus
      are distinguishable, while the inner part hardly exposes any laminar
      configuration on transverse cuts. A marginal plexus with small polygonal or
      rounded small cells appears configured in 3 parts, namely dorsal, intermediate
      and ventral. Outer to the marginal plexus a clear band marks it off from the
      interstitial plexus, which appears more delicate. Within the marginal plexus is
      substantia gelatinosa with rare randomly distributed small or medium-sized cells.
      The inner magnocellular layers consist of clusters of small cells specifically
      allocated to fibre bundles, isolated small cells and large cells, pear-shaped or
      fusiform, appearing either bipolar or multipolar. The marginal and interstitial
      plexuses can represent the framework for modulation and vertical signal
      transmission within the spinal trigeminal nucleus, while the magnocellular layers
      seem to be mainly responsible for contralateral projection. It seems that the
      outer laminae of the spinal trigeminal nucleus may represent the receiver and the
      inner laminae the transmitter of the signal on the trigeminal pathway at
      brainstem level.

PMID- 15478110
TI  - The ossification of the metacarpal and phalangeal bones in human foetuses.
AB  - An evaluation was made of the ossification level of the metacarpal and phalangeal
      bones in human foetuses of both sexes from the 4th to the 9th month of gestation.
      Our results indicate that ossification of phalangeal bones 1 to 5 always started
      at the distal end of the phalanx and endochondral ossification prevailed in the
      proximal phalanx of the thumb.

PMID- 15478111
TI  - Proliferation and apoptosis in the guinea pig adrenal cortex during postnatal
      development.
AB  - The aim of the study was to determine the relation between involution of the FZ
      and the proliferation and apoptosis of the adrenal cortex cells. The study was
      carried out with adrenal glands from guinea pigs aged 1, 3, 9, 14, 21, 35 and 90
      days. Paraffin slices were stained with Mayer haematoxylin and eosin and with
      acid fuchsin. For the immunohistochemical reaction the Anti -PCNA Clone PC10
      (Dako) was used. Apoptosis evaluation was performed with use of the TUNEL method
      (Roche). The results support the theory of involution of the FZ cells realised
      mainly by way of apoptosis. Analysis of the distribution and number of PCNA
      positive cells in the adrenal cortex on subsequent days of PD may also back up
      the migration theory of renewal of the adrenal cortex cells.

PMID- 15478112
TI  - Expression of the apoptotic markers in normal breast epithelium, benign mammary
      dysplasia and in breast cancer.
AB  - Apoptosis and proliferation are processes associated with the development and
      progression of breast cancer. The sensitivity of tumour cells to the induction of
      apoptosis depends on the balance between pro- and anti-apoptotic proteins. The
      expression of Bak and Bcl-2 was examined using an immunohistochemical method in
      71 primary breast cancers. Furthermore, Bcl-2 and Bak were assessed in the normal
      mammary gland as well as in benign mammary dysplasia adjacent to breast cancer.
      Positive immunostaining for Bcl-2 was observed in 77.8% of cases of normal breast
      epithelium (NBE), 93% of benign dysplasia without intraductal proliferation (BBD)
      as well as in 94% of intraductal proliferative lesions of the breast (BIPL).
      Expression of Bak was detected in 39% of cases of NBE, 45% of BBD and in 67% of
      BIPL. In breast cancer Bcl-2 and Bak expression was found in 83% and 70% of the
      cases studied, respectively. Increased Bcl-2 expression in primary tumours
      significantly correlated with favourable prognostic factors, namely pT1, G2 and
      lack of metastases to the regional lymph nodes (p < 0.01, p < 0.03, p < 0.02,
      respectively). There were no relationships between Bak and the
      clinicopathological features studied, but our results indicate changes in the
      expression of Bak during breast cancer development and progression. It would
      appear to be important to assess and compare pro- and anti-apoptotic proteins
      between normal mammary gland, benign mammary dysplasia and the primary tumours of
      breast cancer. This knowledge should be helpful in understanding breast cancer
      development and progression.

PMID- 15478113
TI  - The use of modern techniques of biliary tract monitoring in percutaneous
      drainage.
AB  - The aim of this work is to assess the usefulness of current imaging techniques of
      biliary tracts in percutaneous transhepatic biliary drainage (PTBD). In the
      period from January 1996 to March 2003 44 cases of PTBD were carried out under
      ultrasonographic and X-ray control in 34 patients who could not have a bypass or
      endoscopic prothesis of the bile duct. The effectiveness of the method was
      evaluated in relation to the extent of the intra-hepatic bile ducts, the
      usefulness of simultaneous monitoring (ultrasonography and X-ray) and the
      possibility of preoperative contrasting of the bile ducts. Correct drainage of
      bile ducts was achieved in 43 PTBD. In 6 cases branches of the portal vein were
      pierced during drainage, but thanks to X-ray visualisation this was detected and
      the bile ducts were then drained correctly. During 4 PTBD the grooved probe
      slipped from bile ducts while the catheter was being introduced and a repeated
      prick was necessary. Total cholestasis caused by a tumour does not always bring
      about extension of bile ducts. However, simultaneous ultrasonographic and X-ray
      imaging of the bile ducts enables PTBD to be performed even in patients with a
      slight extension of the duct.

PMID- 15478114
TI  - Intraoperative monitoring of the biliary tracts as a means of preventing
      choledocholithiasis oversight.
AB  - The aim of the work is to assess the performance and effectiveness of
      intraoperative cholangiography or choledochoscopy in the prevention of
      choledocholithiasis oversight. The effectiveness of choledochoscopy was assessed
      in 50 patients during the years 2001-2002. Since 2000 intraoperative
      cholangiography has been performed on all patients after classic cholecystostomy
      in the absence of indications to choledochotomy. The effectiveness of
      intraoperative cholangiography was assessed in 50 patients in 2001. Both groups
      underwent ultrasonographic control and tests of biochemical parameters a year
      after surgery. The advisability of performing intraoperative cholangiography or
      choledochoscopy and their high degree of effectiveness in the prevention of
      choledocholithiasis oversight was confirmed.

PMID- 15478115
TI  - Double-orifice mitral valve and an associated malformation: secundum atrial
      septal defect.
AB  - The authors report a case of double-orifice mitral valve (DOMV) which showed
      mitral stenosis and mild insufficiency. An associated anomaly was secundum atrial
      septal defect. DOMV is an unusual congenital heart defect. The occurrence of this
      anomaly with or without secundum atrial septal defect is very rare. More often it
      is associated with other congenital malformations arising from atrioventricular
      canal defects. There may be no haemodynamic consequences but mitral insufficiency
      and/or stenosis may complicate this malformation. Treatment can be summarised as
      abstention, surgical repair or valve replacement.

PMID- 15478116
TI  - A case of an accessory testicular artery.
AB  - Dissection of an adult male cadaver revealed the presence of an accessory left
      testicular artery in addition to the normal right and left testicular arteries.
      In this case the accessory left testicular artery originated from the
      ventrolateral wall of the descending aorta. The origin was located between the
      superior mesenteric artery and the left renal vein. The accessory artery
      continued to course from the aorta laterally toward the superior ventral portion
      of the left kidney and then passed ventrally to the kidney on its course
      inferiorly to the pelvic region. Communication was observed between the accessory
      left testicular artery and the left renal artery. This variation of gonadal
      vasculature is of interest from the point of view of its embryogenesis, and
      possible clinical significance.

PMID- 15478117
TI  - A case of an anomalous cricothyroid artery.
AB  - The cricothyroid artery typically originates as a branch of the superior thyroid
      artery and courses medially to reach the median cricothyroid ligament. Anatomical
      variations of this pattern are not well documented in the literature. We present
      a case in which the left cricothyroid artery originated from the left superior
      thyroid artery near the superior border of the thyroid cartilage and coursed
      medially to pierce the thyroid lamina. This variation was found during a routine
      anatomy dissection at the American University of the Caribbean School of
      Medicine. The possible clinical implications and their relevance to emergency
      airway management procedures are discussed.

PMID- 15478118
TI  - The middle colic artery originating from the coeliac trunk.
AB  - A case is reported of an anomalous origin of the middle colic artery. The middle
      colic artery originated from the coeliac trunk (CT) instead of the superior
      mesenteric artery, the normal place of origin. The colon receives its blood
      supply from the superior and inferior mesenteric arteries. Since modern colon
      surgery requires a more detailed anatomy of blood supply, many articles have been
      published on the anatomy and variations of the arteries of the colon. However,
      the incidence of such an anomaly is low and there have been few previous reports.
      These arterial variations underscore the importance of performing vascular
      studies prior to major abdominal surgery.

PMID- 15478120
TI  - Automatic domain decomposition of proteins by a Gaussian Network Model.
AB  - Proteins are often comprised of domains of apparently independent folding units.
      These domains can be defined in various ways, but one useful definition divides
      the protein into substructures that seem to move more or less independently. The
      same methods that allow fairly accurate calculation of motion can be used to help
      classify these substructures. We show how the Gaussian Network Model (GNM),
      commonly used for determining motion, can also be adapted to automatically
      classify domains in proteins. Parallels between this physical network model and
      graph theory implementation are apparent. The method is applied to a nonredundant
      set of 55 proteins, and the results are compared to the visual assignments by
      crystallographers. Apart from decomposing proteins into structural domains, the
      algorithm can generally be applied to any large macromolecular system to
      decompose it into motionally decoupled sub-systems.

PMID- 15478121
TI  - Synaptic vesicle cycling at type-identified diaphragm neuromuscular junctions.
AB  - Differences in neuromuscular transmission and neuromuscular junction morphology
      exist across muscle fiber types. We hypothesized that these fiber-type
      differences are reflected in the size of the cycling synaptic vesicle pool.
      Synaptic vesicle cycling at type-identified rat diaphragm neuromuscular junctions
      was examined by fluorescently labeling presynaptic vesicles with FM4-64. We found
      that FM4-64 fluorescence uptake was higher at presynaptic terminals of type I/IIa
      fibers than type IIx/IIb fibers. However, no fiber-type differences in the rate
      of FM4-64 destaining were found with repetitive nerve stimulation. Synaptic
      vesicle density at active zones was examined by transmission electron microscopy.
      In accordance with FM4-64 uptake, synaptic vesicle density was greater at type
      I/IIa than IIx/IIb fibers. These results demonstrate differences in synaptic
      vesicle cycling across diaphragm muscle fiber types, which may underlie
      previously observed differences in neuromuscular transmission across diaphragm
      muscle fiber types. In the diaphragm, motor units comprising type I and type IIa
      fibers are most frequently recruited with a duty cycle of approximately 40%.
      Motor units comprising IIx/IIb fibers are infrequently recruited and only for
      short durations. The capacity for synaptic vesicle release and cycling at
      different muscle fiber types matches the functional requirements of these motor
      units. If the demand for recruitment of motor units comprising IIx/IIb fibers
      increases, for example, with mechanical loading, there is an increased risk for
      neuromuscular transmission failure that my relate to the capacity for synaptic
      vesicle release and cycling. Muscle fiber type-specific adaptations should be
      considered when examining neuromuscular disorders.

PMID- 15478122
TI  - Isoform-specific role of transforming growth factor-beta2 in the regulation of
      proliferation and differentiation of murine adrenal chromaffin cells in vivo.
AB  - Chromaffin cells, the neuroendocrine cells of the adrenal medulla, play an
      important role in molecular, cellular, and developmental neurobiology. Unlike the
      closely related sympathetic neurons, chromaffin cells are able to proliferate
      throughout their whole life span. Proliferation of chromaffin cells in vivo is
      thought to be regulated by the interaction of neurogenic and hormonal signals.
      Previous studies have shown that chromaffin cells synthesize and release
      transforming growth factor-betas (TGF-betas). In the present study, effects of
      TGF-betas on proliferation and differentiation of chromaffin cells in mouse
      adrenal chromaffin cells were investigated in a genetic mouse model. We observed
      a significant increase in the total number of tyrosine hydroxylase-positive
      (TH(+)) cells in Tgfbeta2(-/-) knockout mouse embryos at embryonic day (E) 18.5
      compared with wild-type animals (Tgfbeta2(+/+)), but no changes in the number of
      TH(+) cells were observed in Tgfbeta3(-/-) mouse mutants. At E15.5, but not at
      E18.5, there was a marked increase in the number of proliferative cell nuclear
      antigen-positive chromaffin cells in Tgfbeta2(-/-) knockout embryos compared with
      the wild-type group. On the other hand, there was a clear decrease in the ratio
      of total number of phenylethanolamine-N-methyltransferase-positive cells to the
      total TH(+) in Tgfbeta2(-/-) mice embryos at E18.5 compared with wild-type
      animals. This is the first documentation of the physiological significance of the
      TGF-beta2, an isoform that has been suggested to play a role in the regulation of
      chromaffin cells proliferation and differentiation based on in vitro experiments.

PMID- 15478123
TI  - Amyloid myopathy: characteristic features of a still underdiagnosed disease.
AB  - A 62-year-old man with progressive proximal weakness underwent extensive
      evaluation including muscle biopsy without a clear diagnosis being established. A
      repeat muscle biopsy including Congo red-stained sections revealed infiltration
      of blood-vessel walls and endomysium with amyloid protein, as well as an unusual
      pattern of pathologic changes to muscle fibers. From a review of 79 cases of
      amyloid myopathy reported in the English-language literature, the characteristic
      features of this disorder are described. Congo red-stained sections of muscle
      biopsy viewed under fluorescent or polarized optics, and serum or urine protein
      immunoelectrophoresis, play an important role in the evaluation of myopathy.
      Amyloid myopathy should be a consideration in adults with progressive
      neuromuscular weakness of uncertain cause.

PMID- 15478124
TI  - Flow cytometry: interesting tool for studying binding behavior of DNA on
      inorganic layered double hydroxide (LDH).
AB  - BACKGROUND: A new method was established to characterize the binding kinetics of
      DNA toward layered double hydroxides (LDHs). The setup consisted of a newly
      developed sampling tube that allows the injection of analyte during the flow
      cytometric measurement. METHODS: Layered double hydroxides consist of cationic
      metal hydroxide layers and exchangeable interlayer anions. This negatively
      charged structure permits biomolecules such as DNA to adsorb, and a so-called DNA
      LDH hybrid is formed. The hydroxide layers can be removed in acidic media and the
      DNA will be released. CERATOFIX (a registered trademark of Sud-Chemie AG NA that
      belongs to the family of LDHs, produced by Sud-Chemie AG). The chemical structure
      can be summarized as [Mg(2)Al(OH)(6)](CO(3))(0.5). The binding capacity and
      kinetic characteristics of different types of CERATOFIX NA for a model DNA was
      determined by flow cytometry. RESULTS: The static binding capacities of the
      different LDHs were determined after 1- and 16-h incubation with DNA solution,
      showing different binding patterns between the LDH materials. The binding
      kinetics were revealed by flow cytometric measurements in short-term and long
      term kinetic experiments, showing that the majority of DNA adsorbs within the
      first 60 s. CONCLUSIONS: DNA removal from cell culture supernatants is one of the
      major concerns in downstream processing. Due to the anion exchange capabilities
      of LDHs it seemed a very interesting approach to use these materials for binding
      of DNA for elimination purposes.

PMID- 15478125
TI  - Sulfamates and their therapeutic potential.
AB  - Starting from the very simple molecule sulfamic acid, O-substituted-, N
      substituted-, or di-/tri-substituted sulfamates may be obtained, which show
      specific biological activities which were or started to be exploited for the
      design of many types of therapeutic agents. Among them, sulfamate inhibitors of
      aminoacyl-tRNA synthetases (aaRSs) were recently reported, constituting
      completely new classes of antibiotics, useful in the fight of drug-resistant
      infections. Anti-viral agents incorporating sulfamate moieties have also been
      obtained, with at least two types of such derivatives investigated: the
      nucleoside/nucleotide human immunodeficiency virus (HIV) reverse transcriptase
      inhibitors, and the HIV protease inhibitors (PIs). In the increasing
      armamentarium of anti-cancer drugs, the sulfamates occupy a special position,
      with at least two important targets evidenced so far: the steroid sulfatases
      (STSs) and the carbonic anhydrases (CAs). An impressing number of inhibitors of
      STSs of the sulfamate type have been reported in the last years, with several
      compounds, such as 667COUMATE among others, progressing to clinical trials for
      the treatment of hormone-dependent tumors (breast and prostate cancers). This
      field is rapidly evolving, with many types of new inhibitors being constantly
      reported and designed in such a way as to increase their anti-tumor properties,
      and decrease undesired features (for example, estrogenicity, a problem
      encountered with the first generation such inhibitors, such as EMATE). Among the
      many isozymes of CAs, at least two, CA IX and CA XII, are highly overexpressed in
      tumors, being generally absent in the normal tissues. Inhibition of tumor
      associated CAs was hypothesized to lead to novel therapeutic approaches for the
      treatment of cancer. Many sulfamates act as very potent (low nanomolar) CA
      inhibitors. The X-ray crystal structure of the best-studied isozyme, CA II, with
      three sulfamates (sulfamic acid, topiramate, and EMATE) has recently been
      reported, which allowed for a rationale drug design of new inhibitors. Indeed,
      low nanomolar CA IX inhibitors of the sulfamate type have been reported, although
      such compounds also act as efficient inhibitors of isozymes CA I and II, which
      are not associated with tumors. A large number of anti-convulsant sulfamates have
      been described, with one such compound, topiramate, being widely used clinically
      as anti-epileptic drug. By taking into consideration a side effect of topiramate,
      an anti-epileptic drug leading to weight loss in some patients, it has recently
      been proposed to use this drug and related sulfamates for the treatment of
      obesity. The rationale of this use is based on the inhibition of the
      mitochondrial CA isozyme, CA V, involved in lipogenesis. Some sulfamates were
      also shown to possess potent inhibitory activity against acyl coenzyme
      A:cholesterol acyltransferase, an enzyme involved in cholesterol metabolism. One
      such agent, avasimibe, is in advanced clinical trials for the treatment of
      hyperlipidemia and atherosclerosis. Thus, the sulfamate moiety offers very
      attractive possibilities for the drug design of various pharmacological agents,
      which are on one hand due to the relative ease with which such compounds are
      synthesized, and on the other one, due to the fact that biological activity of
      most of them is impressive.

PMID- 15478126
TI  - Eating behavior disorders in Chilean infants.
AB  - Eating behavior disorders (EBD) are often observed in children. Most of the
      related research, however, has been performed in developed countries. In
      countries like Chile, characterization of food disorders during the first years
      of life is unknown. OBJECTIVE: The goal of the current study is to characterize
      the EBD of Chilean children during the first 2 years of life. METHODS: We studied
      67 children (mean age = 5.4 months; range = 4-24 months). The study group (SG;
      according to criteria in the 4th ed. of the Diagnostic and Statistical Manual of
      Mental Disorders) consisted of 34 children with EBD whose mothers spontaneously
      consulted for difficulties for feeding and the control group (CG) included 33
      healthy children. A structured recall was applied to their mothers. RESULTS: EBD
      onset was observed more frequently during the first semester of life and was
      associated with new foods. The children in the SG presented with lower birth
      weight (SG: 3,000 +/- 500 g; CG: 3,400 +/- 500 g; p < .001), weight/length (-0.4
      +/- 1.0 vs. 0.8 +/- 1.1; p = .0001), and length/age z scores (-0.7 +/- 1.0 vs. 
      0.1 +/- 0.8; p = .007) than children in the CG. Early weaning before 4 months of
      age was more frequently found in the SG (44.1% vs. 12.1%; p = .04). The logistic
      regression showed as variables those associated with EBD, that is, birth weight
      and maternal history of EDB during her infancy (chi(2), p = .0003). Mothers of
      children in the SG felt that their maternal role was more difficult and less
      satisfactory than mothers of children in the CG (chi(2), p = .03). DISCUSSION:
      EBDs in Chilean infants are observed during the first months of life and are
      associated with a lower birth weight, shortened exclusive breast-feeding,
      maternal history of EBD during their infancy, and lower physical growth. Mothers
      of children with EBD frequently feel that their maternal role is difficult and
      unsatisfactory.

PMID- 15478127
TI  - Cyclization of pyrrhocoricin retains structural elements crucial for the
      antimicrobial activity of the native peptide.
AB  - Pyrrhocoricin is a naturally occurring antimicrobial peptide from the European
      fire bug Pyrrhocoris apterus. It has submicromolar activity against a range of
      Gram-negative bacterial strains and has created recent interest as a lead for the
      development of novel antibiotic compounds. In this study, we have used NMR
      spectroscopy to determine the solution structures of pyrrhocoricin and a
      synthetic macrocyclic derivative that has improved in vivo pharmaceutical
      properties. Native pyrrhocoricin is largely disordered in solution, but there is
      evidence of a subpopulation with ordered turn regions over residues 2-5, 4-7, and
      16-19. The macrocyclic derivative incorporates a nine amino acid linker joining
      the N- and C-termini, which does not adversely affect the antimicrobial potency
      but leads to a broader spectrum of activity. The NMR data suggest that the turn
      conformations in the cyclic derivative are similar to those in the native form,
      thus implicating them in the biological function.

PMID- 15478128
TI  - Time course of symptom remission in eating disorders.
AB  - OBJECTIVE: The study was carried out to test whether time to remission varies for
      different eating disorder symptoms. METHOD: Sixty-five patients (35 anorexic
      patients and 30 bulimic patients) treated with psychotherapy were interviewed 2
      1/2 years after initial assessment. RESULTS: The anorexic physical symptoms
      remitted before the psychological symptoms of anorexia and bulimia nervosa, as
      did the bulimic behaviors: binging and purging. Nonpurging compensatory behavior
      and obsession with weight and shape were the last symptoms to remit. Differences
      between the anorexic and bulimic groups were found between the remission order of
      psychological symptoms. DISCUSSION: In spite of different treatments and symptoms
      between patients, the results support the notion of a common pattern in the
      process of change including a long and stepwise course. The results detail a
      template of the course to recovery for eating disorders.

PMID- 15478129
TI  - Genetic and environmental influences on binge eating in the absence of
      compensatory behaviors: a population-based twin study.
AB  - OBJECTIVE: The current study explores the extent to which genetic and
      environmental factors influence liability to binge eating in the absence of
      compensatory behaviors (BE) in a population-based sample of twins. METHOD:
      Questionnaire data on 8,045 same-sex and opposite-sex twins, aged 18-31 years,
      from a Norwegian twin registry were used to assess BE during the last 6 months.
      RESULTS: The best-fitting biometrical model suggested that the heritability of BE
      was 41% (95% confidence interval [CI]: 0.31-0.50). Individual environmental
      factors accounted for the rest of the variance (59%; 95% CI: 0.50-0.69). No
      significant sex differences were found, but the statistical power to detect such
      effects was low. Shared environmental influences on the liability to BE in males
      could not be ruled out. DISCUSSION: The findings indicate significant additive
      genetic influences on BE, supporting the validity of the core features of binge
      eating disorder as a diagnostic category.

PMID- 15478130
TI  - Managing the chronic, treatment-resistant patient with anorexia nervosa.
AB  - OBJECTIVE: To describe the psychopathology of chronic, treatment-resistant
      anorexia nervosa, as well as a paradigm for its clinical management. METHOD: The
      foundation of the approach integrates clinical experience, empirical
      psychological findings, and a conceptual understanding of developmental and
      phenomenologic aspects of the illness. RESULTS: Elements of the management
      paradigm take account of the compensatory nature of illness chronicity. The
      inherent risks of treating these patients in the customary way are described,
      along with therapist countertransference that must be anticipated and effectively
      considered. DISCUSSION: The chronically ill patient requires a unique approach to
      care, one that minimizes the risk of iatrogenic effects of rapid weight
      restoration or failure to appraise the deleterious influences of therapist
      countertransference.

PMID- 15478131
TI  - A qualitative study of the experience of caring for a person with bulimia
      nervosa. Part 1: The emotional impact of caring.
AB  - OBJECTIVE: Family carers of individuals with mental disorders have been found to
      experience mental health difficulties of their own. There has been little
      research into the impact of caring for individuals with eating disorders. A
      preliminary study found that carers of individuals with anorexia nervosa
      experience more difficulties and distress than carers of people with psychoses
      (Treasure et al., [2001]. Social Psychiatry and Psychiatric Epidemiology, 36, 343
      347). This is the first study to qualitatively investigate the experiences of
      carers of individuals with bulimia nervosa (BN). METHOD: Twenty carers of
      individuals with BN were interviewed using a semistructured interview. Interviews
      were transcribed and the texts analyzed using content analysis to identify
      themes. RESULTS: The principal themes to emerge were the impact of the discovery
      of BN on the carer, the ongoing impact of care-giving, coping strategies used by
      the carer, and the positive impact of the illness for both the carers and the
      persons in their care. DISCUSSION: BN has a potent impact on carers' lives. This
      has implications in terms of service provision and future research in this area.

PMID- 15478132
TI  - No longer just a pretty face: fashion magazines' depictions of ideal female
      beauty from 1959 to 1999.
AB  - OBJECTIVE: The print media's depiction of the ideal of feminine beauty as
      presented to American women was examined for the years 1959-1999. METHOD: Trends
      were investigated through an analysis of cover models appearing on the four most
      popular American fashion magazines. RESULTS: Body size for fashion models
      decreased significantly during the 1980s and 1990s. There was also a dramatic
      increase in the frequency with which the media depicted the entire bodies of the
      models from the 1960s to the 1990s. DISCUSSION: Both the increasingly thin images
      and the striking increase in full-body portrayals suggest an increase in the
      value placed by American society on a thin ideal for women, a change that is
      concurrent with the increase in disturbed eating patterns among American women.

PMID- 15478133
TI  - An audit of a British sample of death certificates in which anorexia nervosa is
      listed as a cause of death.
AB  - OBJECTIVE: Anorexia nervosa is associated with an increased mortality rate.
      National mortality statistics based on statutory death certification are
      potentially an important source of information. However, there are reasons to
      believe that these statistics may be subject to significant errors. An audit of
      the quality of information and diagnosis was conducted on death certificates in
      which anorexia nervosa was mentioned. METHOD: The current study examined data
      from death certificates of people who died in England and Wales between 1993 and
      1999. RESULTS: There were 230 such deaths, but only 128--just over one half--were
      rated as likely to be deaths associated with true anorexia nervosa. DISCUSSION:
      National mortality statistics derived from death certificates are a flawed source
      of information on deaths from anorexia nervosa when taken at face value. There
      may be both underreporting and overreporting. Detailed examination may improve
      their usefulness by reducing the overerreporting. It seems likely that the
      association of deaths with anorexia nervosa is systematically underreported.

PMID- 15478134
TI  - Changes in weight and body image over time in women with eating disorders.
AB  - BACKGROUND: This study examined the changes in body image and weight in young
      women with an adolescent eating disorder, relative to women without an eating
      disorder (noED). METHOD: Three diagnostic groups, anorexia nervosa (AN; n = 10),
      bulimia nervosa (BN; n = 27), and binge eating disorder (BED; n = 42) and three
      comparison groups (noED; n = 659 each) were compared on body mass index (BMI) and
      self-reported current body size, ideal body size, and weight dissatisfaction.
      Dependent variables were examined 2 and 1 year before the onset, the onset year,
      and 1 and 2 years after the onset of the eating disorder in a model that was
      adjusted for ethnicity and BMI. RESULTS: BMI was lower in the AN group at all
      time points except 2 years before onset. AN girls evidenced a significantly
      stronger relation between BMI and current self-ratings and weight dissatisfaction
      than noED girls. BMI did not differ between the BN group and the noED group.
      Girls with BN reported larger current body sizes and greater weight
      dissatisfaction across all time points. The BED group had higher BMI than the
      noED group across time. BED girls reported greater current body size ratings and
      weight dissatisfaction than the noED girls. Girls with AN, BN, or BED did not
      differ from the noED girls on body ideal ratings. DISCUSSION: Body weight seems
      to influence perception of body size more so for girls with AN than for noED
      girls. No support was found for an accelerated weight gain over time for BN.
      Weight may increase over time for the BED group relative to the noED group, but
      larger studies are needed. Across all three groups, ideal body size appears to be
      unrelated to diagnostic status. Rather, the risk for developing an eating
      disorder appears to arise from size overestimation and related weight
      dissatisfaction.

PMID- 15478135
TI  - Stress and hunger alter the anorectic efficacy of fluoxetine in binge-eating rats
      with a history of caloric restriction.
AB  - OBJECTIVE: We examined the effect of fluoxetine to suppress binge eating in rats
      with a history of caloric restriction (CR) and the extent to which this effect
      was altered by stress and hunger. METHOD: To detect heightened sensitivity to
      fluoxetine, young female rats were used to determine a subthreshold anorectic
      dose (2 mg/kg, intraperitonally). Another group of rats was either fed ad libitum
      or given multiple CR (to 90% body weight) and refeeding-to-satiety cycles. One
      half of the rats were then either spared or subjected to foot shock stress before
      fluoxetine treatment. RESULTS: A history of CR alone produced bingelike eating on
      palatable food (p < .001) and, although stress did not affect intake, it rendered
      CR rats hypersensitive to the satiety effect of fluoxetine. The feeding
      suppression was mainly for chow (p < .05) and the effect was abolished if the
      rats were in negative energy balance. DISCUSSION: Results support the utility of
      this animal model to elucidate serotonergic changes linking dieting to binge
      eating. The diverse effects of fluoxetine on the type of food, and in hungry
      versus sated rats, suggest alternate brain mechanisms should be concomitantly
      targeted for improved treatment of binge eating disorders.

PMID- 15478136
TI  - A qualitative study of the experience of caring for a person with bulimia
      nervosa. Part 2: Carers' needs and experiences of services and other support.
AB  - OBJECTIVE: Family carers of people with mental disorders have specific needs to
      safeguard their own mental health. The needs of carers of individuals with eating
      disorders have received little attention. A focus group with carers of people
      with anorexia nervosa identified a number of specific needs (Haigh & Treasure
      [2003]. European Eating Disorders Review, 11(2), 125-141). However, there has
      been no published research into the needs of carers of individuals with bulimia
      nervosa (BN). METHOD: Twenty carers of individuals with BN were interviewed using
      a semistructured interview schedule. Interviews were transcribed and the texts
      were analyzed using a content analysis approach to identify themes. RESULTS:
      Carers expressed the need for more information, practical advice, guidance, and
      the need to talk to others about their experiences. DISCUSSION: Further research
      is recommended to explore how the needs expressed by carers may best be
      translated into services that effectively meet the requirements of both patients
      and carers and reduce the risk to carers' mental health.

PMID- 15478137
TI  - Screening for eating disorders and high-risk behavior: caution.
AB  - OBJECTIVE: The current study reviews the state of eating disorder screens.
      METHODS: Screens were classified by their purported screening function:
      identification of cases with (a) anorexia nervosa only; (b) bulimia nervosa only;
      (c) eating disorders in general; (d) partial syndrome, eating disorder not
      otherwise specified (EDNOS), or subclinical; (e) not a-d but at high risk.
      Information is presented on development, psychometric properties, and external
      validation (e.g., sensitivity, specificity, positive predictive values, and
      negative predictive values). RESULTS: Screens differ widely with regard to
      objective, psychometric properties and the validation methodology used. Most
      screens that identify cases are not appropriate for the identification of at-risk
      behaviors. Little data on the external validity of screens are available.
      DISCUSSION: Screens should be used with caution. A sequential procedure, in which
      subjects identified as being at risk during the first stage is followed by more
      specific diagnostic tests during the second stage, might overcome some of the
      limitations of the one-stage screening approach.

PMID- 15478139
TI  - Aromatic interactions in peptides: impact on structure and function.
AB  - Aromatic interactions, including pi-pi, cation-pi, aryl-sulfur, and carbohydrate
      pi interactions, have been shown to be prevalent in proteins through protein
      structure analysis, suggesting that they are important contributors to protein
      structure. However, the magnitude and significance of aromatic interactions is
      not defined by such studies. Investigation of aromatic interactions in the
      context of structured peptides has complemented studies of protein structure and
      has provided a wealth of information regarding the role of aromatic interactions
      in protein structure and function. Recent advances in this area are reviewed.

PMID- 15478140
TI  - Preparation and characterization of a highly macroporous biodegradable composite
      tissue engineering scaffold.
AB  - A unique composite scaffold for bone-tissue engineering applications has been
      prepared by combining biodegradable poly(lactide-co-glycolide) (PLGA) with
      bioresorbable calcium phosphate (CaP) cement particles through the process of
      particle fusion and phase separation/particle leaching. The scaffold is
      characterized by a highly interconnected macroporosity, with macropores of 0.8
      1.8 mm and porosities ranging from 81% to 91%, and improved mechanical properties
      with respect to the polymer alone, producing excellent dimensional stability. The
      scaffold properties were controlled by adjusting the processing parameters,
      including PLGA molar mass and concentration, CaP/PLGA ratio, and porogen size.
      The differences in mechanical properties between dry, wet/room temperature, and
      wet/37 degrees C testing conditions, of which the latter are more relevant for
      materials to be employed in a biological milieu, were investigated. Thus, a
      scaffold made from PLGA IV 1.13, PLGA concentration 12.5%, and CaP/PLGA ratio 2:1
      exhibited significantly different compressive strengths of 0.16 MPa and 0.04 MPa
      when tested under dry and wet/37 degrees C conditions, respectively. .

PMID- 15478141
TI  - 3D real time methodology monitoring cement failures in THA.
AB  - The present work proposed a methodology to monitor cement microcrack formation in
      the cemented femoral stem construct using the acoustic emission technique. This
      technique provides a unique means to automatically tally the number of
      microcracks, to visualize microcrack distribution, and to animate the progress of
      crack formation in a given time window of a fatigue test. In this work, the
      formulation of microcrack source location was derived and a computer program was
      developed specifically for the proposed application. The program was validated
      using computer simulation and standard pencil lead break tests. It was found that
      the mathematical errors complied with the acceptable minimal error. Based on the
      pencil lead break tests, the average technical error used to estimate the
      resolution of this technique was 4.7 mm at the present stage. The program was
      then used to monitor the fatigue damage in precoated cemented femoral hip
      constructs loaded for a total of more than five million cycles. Two types of
      microcrack activities were observed in the experiments: Type I and Type II
      microcracks. A Type I microcrack was a crack that was captured by four or more
      sensors, and therefore its location was defined uniquely by a set of coordinates.
      A Type II microcrack was a crack that was captured by three or less sensors,
      therefore it was unlocatable. Both counts of Type I and Type II microcrack were
      tallied with respect to the day of fatigue tests. Acoustic emission microcrack
      graphs were used to visualize the distribution of Type I microcracks in the
      construct. It was found that the Type I microcracks distributed mainly over the
      proximal third of the stem. The amount of microcrack events decreased
      significantly as the number of loading cycles increased.

PMID- 15478142
TI  - Utilization of low-volume hospitals for total hip replacement.
AB  - OBJECTIVE: To identify factors associated with utilization of low-volume
      hospitals for total hip replacement (THR) and to estimate differences in the
      distances that Medicare beneficiaries had to travel to reach low- or high-volume
      hospitals. METHODS: We studied a population-based sample of 1,146 Medicare
      beneficiaries who underwent elective THR in 1995. Using multiple data sources
      including medical record review, Medicare claims data, 1990 Census data, and a
      patient survey, we examined factors independently associated with utilization of
      low-volume hospitals for elective THR. We estimated the magnitude of difference
      in distances for patients undergoing THR in low- and high-volume hospitals. We
      determined the distance between each patient's residence and the treating
      hospital using MapQuest. RESULTS: Rural residency, low income, and low
      educational attainment, as well as belief in the importance of convenient
      location in the choice of hospital, were associated with higher utilization of
      low-volume hospitals. Rural and suburban patients who went to low-volume
      hospitals traveled much less than patients operated upon in high-volume centers.
      CONCLUSION: Policies aimed at restricting THR to high-volume centers would
      differentially affect poor, less educated, and rural patients. Voluntary efforts
      to shift THR to high-volume centers should involve educating these patients and
      their referring physicians about differences in both short-term and longer-term
      outcomes between high- and low-volume centers.

PMID- 15478143
TI  - Glucocorticoid therapy in giant cell arteritis: comment on the article by Proven
      et al.

PMID- 15478144
TI  - Health of children with chronic arthritis: relationship of different measures and
      the quality of parent proxy reporting.
AB  - OBJECTIVE: To examine the strength of the association between different measures
      of health-related quality of life (HRQOL), disability, pain, and well-being in
      children with chronic arthritis. To evaluate whether HRQOL scores vary as a
      function of disability status beyond chance. To assess the quality of the parent
      proxy report for HRQOL as compared with disability, pain, and well-being.
      METHODS: Measures of HRQOL (visual analog scale [VAS] of health, Pediatric
      Quality of Life Inventory [PedsQL], Juvenile Arthritis Quality of Life
      Questionnaire (JAQQ), and modified standard gamble technique [SG]), disability
      (Childhood Health Assessment Questionnaire), VAS of pain, and VAS of well-being
      (VAS-well) were completed by the parents (n = 119) and patients > or =8 years
      (SG: > or =12 years). RESULTS: HRQOL was highest when measured by the SG, whose
      utilities were no more than weakly correlated with any of the other outcomes. The
      values of all other HRQOL measures were at least moderately correlated with each
      other and with the VAS-well. Irrespective of the measure used, disability was
      associated with significantly decreased HRQOL. There was fair to good agreement
      and moderate consistency of the HRQOL ratings (SG: fair consistency) between
      patients and parents with marked differences between health domains. CONCLUSION:
      HRQOL measured by the PedsQL, JAQQ, and VAS are moderately to highly correlated
      with each other in children with chronic arthritis. The children's HRQOL
      significantly decreases with increasing disability. Despite more pronounced
      differences for some health domains, parents are moderate to good proxy reporters
      of HRQOL, disability, and well-being of children with chronic arthritis.

PMID- 15478145
TI  - Reliability and validity of the proposed American College of Rheumatology
      neuropsychological battery for systemic lupus erythematosus.
AB  - OBJECTIVE: To examine the reliability and validity of the proposed American
      College of Rheumatology (ACR) neuropsychological battery for patients with
      systemic lupus erythematosus (SLE). METHODS: Thirty-one SLE patients with a
      history of neuropsychiatric symptoms (NPSLE), 22 SLE patients without a history
      of neuropsychiatric symptoms (non-NPSLE), and 25 healthy controls completed
      measures of cognition at baseline and after 1 month. The 1-hour proposed ACR-SLE
      battery was compared with a 4-hour comprehensive battery (CB). RESULTS: Seven of
      12 measures from the ACR-SLE battery were lower in SLE patients compared with
      controls. Overall agreement between impairment on the ACR-SLE battery and the CB
      was 90%. This was established using previously defined impairment on the CB and 4
      of 12 scores impaired on the ACR-SLE battery. Almost perfect agreement between
      the 2 batteries was found for non-NPSLE patients and healthy controls (95-96%)
      and moderate agreement was reported for NPSLE patients (81%). Intraclass
      correlation coefficients for ACR-SLE tests ranged from 0.40 to 0.90, indicating
      adequate reliability. CONCLUSION: Reliability and validity of the ACR-SLE battery
      was established in this study. Agreement regarding classification for impairment
      was almost perfect for non-NPSLE and moderate for the NPSLE patients. The ACR
      battery is well designed for general classification of cognitive impairment in
      SLE. However, comprehensive testing may be useful in identifying specific
      deficits in NPSLE.

PMID- 15478146
TI  - Serum levels of matrix metalloproteinase 3 and macrophage colony-stimulating
      factor 1 correlate with disease activity in ankylosing spondylitis.
AB  - OBJECTIVE: To assess the usefulness of measuring serum matrix metalloproteinase 3
      (MMP-3) and macrophage colony-stimulating factor (M-CSF) in patients with
      ankylosing spondylitis (AS). METHODS: Serum levels of MMP-3 and M-CSF were
      measured in AS patients who did and did not receive infliximab treatment. These
      were compared with those of 28 healthy subjects. RESULTS: In the group of AS
      patients not treated with biologics, both M-CSF and MMP-3 correlated with the
      Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) values, but not with
      each other. Logistic regression analysis showed that MMP-3 values were high in
      those with severely active disease. Infusions of infliximab in AS patients led to
      a significant decrease in the values of the BASDAI as well as the serum MMP-3,
      but no change in the serum M-CSF values. CONCLUSION: MMP-3 and M-CSF are
      potentially useful markers of AS disease activity.

PMID- 15478147
TI  - Comparison of manual therapy and exercise therapy in osteoarthritis of the hip: a
      randomized clinical trial.
AB  - OBJECTIVE: To determine the effectiveness of a manual therapy program compared
      with an exercise therapy program in patients with osteoarthritis (OA) of the hip.
      METHODS: A single-blind, randomized clinical trial of 109 hip OA patients was
      carried out in the outpatient clinic for physical therapy of a large hospital.
      The manual therapy program focused on specific manipulations and mobilization of
      the hip joint. The exercise therapy program focused on active exercises to
      improve muscle function and joint motion. The treatment period was 5 weeks (9
      sessions). The primary outcome was general perceived improvement after treatment.
      Secondary outcomes included pain, hip function, walking speed, range of motion,
      and quality of life. RESULTS: Of 109 patients included in the study, 56 were
      allocated to manual therapy and 53 to exercise therapy. No major differences were
      found on baseline characteristics between groups. Success rates (primary outcome)
      after 5 weeks were 81% in the manual therapy group and 50% in the exercise group
      (odds ratio 1.92, 95% confidence interval 1.30, 2.60). Furthermore, patients in
      the manual therapy group had significantly better outcomes on pain, stiffness,
      hip function, and range of motion. Effects of manual therapy on the improvement
      of pain, hip function, and range of motion endured after 29 weeks. CONCLUSION:
      The effect of the manual therapy program on hip function is superior to the
      exercise therapy program in patients with OA of the hip.

PMID- 15478148
TI  - Predicting mortality in systemic Wegener's granulomatosis: comment on the article
      by Bligny et al.

PMID- 15478149
TI  - High prevalence of symptomatic enthesopathy of the shoulder in ankylosing
      spondylitis: deltoid origin involvement constitutes a hallmark of disease.
AB  - OBJECTIVE: To examine the prevalence and characteristics of shoulder involvement
      in ankylosing spondylitis (AS). To analyze the sensitivity and specificity of
      shoulder lesions defined by magnetic resonance imaging (MRI) in patients with AS.
      METHODS: Prevalence of shoulder involvement was ascertained by chart review of
      400 AS patients. One hundred of these patients and 285 controls were selected for
      clinical evaluation. AS patients with a clinically defined shoulder disorder (n =
      15) and a control group of 91 patients (94 shoulders) with nonspecific shoulder
      pain were studied with MRI. Fifty-four MRI-defined variables per shoulder were
      analyzed by 2 observers. A third cohort of patients with AS (n = 76) was
      prospectively evaluated by clinical exam for AS-specific shoulder lesions
      identified on MRI. RESULTS: Shoulder pain was recorded in 3.5% of patients by
      chart review. Shoulder involvement by clinical evaluation was noted in 24.7% of
      patients versus 14.2% of controls (odds ratio [OR] 8.17, 95% confidence interval
      [95% CI] 3.14-21.28, P < 0.001). Rotator cuff tendinitis was significantly more
      prevalent in patients (15.1%) than controls (3.5%; OR 8.17, 95% CI 2.66-25.14, P
      < 0.001). Acromioclavicular joint arthrosis was the most common lesion observed
      in AS shoulders (94%), although specificity was low (32%). Bone marrow edema at
      any entheseal site was noted in significantly more AS shoulders (70.6%) than in
      control (19.1%) shoulders (P < 0.001, corrected P = 0.02). Erosion of the greater
      tuberosity with or without adjacent bone edema had the best combination of
      sensitivity (58-65%) and specificity (86-92%). Intense acromial entheseal edema
      at the deltoid origin was observed only in AS shoulders (41.2%; P < 0.001).
      Evaluation of a prospective cohort of patients with AS showed that 22.4% had
      rotator cuff enthesopathy. CONCLUSION: Shoulder lesions in AS are common and
      characterized clinically by rotator cuff tendinitis and on MRI by intense bone
      edema localized to the supraspinatus/greater tuberosity and deltoid/acromial
      entheses. Intense acromial bone edema at the deltoid origin is a hitherto
      undescribed and highly specific feature of AS. Enthesopathy of the rotator cuff
      is underrecognized in AS and should be incorporated into instruments measuring
      enthesitis.

PMID- 15478150
TI  - Reliability and validity of the Duruoz Hand Index in persons with systemic
      sclerosis (scleroderma).
AB  - OBJECTIVE: To examine the test-retest reliability and concurrent validity of the
      Duruoz Hand Index (DHI) in persons with scleroderma. METHODS: Forty patients with
      scleroderma and no other major medical problems completed the DHI at 2 points in
      time to assess test-retest reliability. To assess validity, participants were
      administered the Arthritis Hand Function Test (AHFT), the Hand Mobility in
      Scleroderma Test (HAMIS), and the Keital Function Test (KFT), all performance
      based tests. In addition, participants completed the Health Assessment
      Questionnaire (HAQ), a self report of functional ability. RESULTS: Test-retest
      reliability intraclass correlation coefficients for the DHI ranged from 0.81 to
      0.97. Scores on the DHI did not correlate with HAMIS scores, but were
      significantly correlated with scores from the KFT (rs = 0.48, P < 0.01), HAQ (rs
      = 0.79, P < 0.01), and all sections of the AHFT (rs = 0.34-0.60, P < 0.05-0.01).
      CONCLUSION: The results from this study show the DHI to be a reliable and valid
      test for persons with scleroderma.

PMID- 15478152
TI  - Longitudinal comparison of the Health Assessment Questionnaire (HAQ) and the
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).
AB  - OBJECTIVE: To compare the measurement properties of the generic Health Assessment
      Questionnaire (HAQ) and the disease-specific Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC). METHODS: Physical function, pain, and
      radiographic progression were assessed in knee or hip osteoarthritis patients (n
      = 271) who had 2 radiographs that were at least 6 months apart from 6 ARAMIS
      (Arthritis, Rheumatism, and Aging Medical Information System) databanks. Data
      were compared at baseline and after a mean of 3.2 (SE 0.10) years. Correlation
      coefficients and standardized effect sizes (SES) were used to assess their
      relationship and responsiveness. RESULTS: The majority of items in the 2 function
      and pain scales overlapped and were highly and significantly correlated with each
      other at baseline and last assessments (function at baseline rs = 0.71 and
      function at last assessment rs = 0.79, P < 0.0001; pain at baseline rs = 0.70 and
      pain at last assessment rs = 0.76, P < 0.0001). The HAQ disability index and
      total knee score were more sensitive to detection of disease progression than the
      WOMAC (SES for HAQ = 0.27; SES for WOMAC = -0.05). CONCLUSION: Both instruments
      showed favorable measurement properties, with the HAQ having the advantages of
      being more sensitive to change and adaptable to a wide variety of diseases and
      conditions, which contribute to the generalizability of findings.

PMID- 15478153
TI  - Measuring the consequences of osteoarthritis and joint pain in population-based
      studies: can existing health measurement instruments capture levels of
      participation?
AB  - OBJECTIVE: To identify health measurement instruments to investigate levels of
      participation associated with joint pain in a population survey questionnaire.
      METHOD: A comprehensive electronic search of the published literature was
      performed to identify potential instruments that could measure participation. All
      items from identified instruments were assessed for the ability to measure
      participation by 2 experienced and 2 inexperienced assessors. Agreement was
      determined in terms of actual agreement (%) and agreement beyond chance (kappa).
      RESULTS: Twenty-seven instruments (912 items) were identified. Agreement between
      the experienced assessors occurred in 86% of items (kappa = 0.70, 95% confidence
      interval [95% CI] 0.65-0.75) and between the inexperienced assessors in 72%
      (kappa = 0.40, 95% CI 0.34-0.46). The greatest proportion of participation items
      in one instrument was 82%. CONCLUSION: None of the identified instruments
      consisted entirely of participation items. The concept of participation and its
      translation into measurement for use in the general population is likely to need
      further development.

PMID- 15478154
TI  - Motivational interviewing may encourage exercise in persons with fibromyalgia by
      enhancing self efficacy.

PMID- 15478156
TI  - Psychosocial and geriatric correlates of functional status after total hip
      replacement.
AB  - OBJECTIVE: To determine whether psychosocial factors, chronic diseases, and
      common geriatric problems are associated with poor physical function 3 years
      after primary total hip replacement (THR). METHODS: We studied a sample of
      Medicare recipients in Ohio, Pennsylvania, and Colorado (n = 922) who underwent
      primary THR in 1995 (mean +/- SD age 73.1 +/- 5.6 years, 32% men). Participants
      completed a questionnaire regarding lifestyle factors, medical history, and
      quality of life approximately 3 years after the surgery. Physical function was
      measured using the function subscale of the Western Ontario and McMaster
      Universities Osteoarthritis Index. We assessed the relationship between
      functional outcome 3 years postsurgery and 4 predictor domains: pain or
      complications in the operated hip, other musculoskeletal comorbidity, medical
      factors (obesity, chronic medical comorbidity, rheumatoid arthritis, and such
      common geriatric problems as falls, poor balance, or incontinence), and
      psychosocial factors (mental health, regular alcohol consumption, smoking,
      provider role, living alone, and education). RESULTS: Ten percent of subjects had
      poor functional status. In a logistic regression model controlling for sex and
      age, the following factors were associated with an increased risk for poor
      functional status (in order of importance): pain in the back or lower extremity,
      severe pain in the operated hip, poor mental health, more than 1 common geriatric
      problem, obesity, and less than college education. CONCLUSION: Pain in the
      operated hip was strongly associated with poor functional status 3 years after
      THR. However, other factors associated with poor functional status were not
      related to the hip. Our results suggest that a comprehensive assessment of
      functional status in elderly THR patients should include assessment of common
      geriatric problems, mental health status, and weight.

PMID- 15478157
TI  - Genetics of rheumatoid arthritis: Is there a pattern predicting extraarticular
      manifestations?

PMID- 15478158
TI  - A crossover trial of custom-made and commercially available wrist splints in
      adults with inflammatory arthritis.
AB  - OBJECTIVE: To compare the effect of 3 wrist splints (2 prefabricated commercial
      splints and 1 custom made) on perceived wrist pain, hand function, and perceived
      upper extremity function in adults with inflammatory arthritis. METHODS: Subjects
      (n = 45, mean age 49 years, mean disease duration 8.6 years) were randomly
      assigned to treatment order in a 3-phase crossover trial. Splints were worn for 4
      weeks, separated by 1-week washouts. Outcomes were assessed at baseline, after
      each splint phase and washout period, and at 6 months' followup using a pain
      visual analog scale (VAS), the Arthritis Hand Function Test, and McMaster-Toronto
      Arthritis Patient Function Preference questionnaire. Data were analyzed with
      multivariate analyses of variance (MANOVAs), t-tests, and chi-square tests.
      RESULTS: There did not appear to be order or carryover effects. MANOVA indicated
      that wrist splints significantly reduced pain (P = 0.007). The custom leather
      splint was most effective in reducing pain, from 4.1 cm to 2.8 cm on the VAS (P =
      0.001). All splints improved hand strength, and the commercial Rolyan splint
      provided significantly stronger grip than the Anatech commercial splint (P =
      0.04). In contrast to previous studies, splints did not compromise dexterity.
      There were several significant differences among splints, depending on the
      outcome measure. Improvements were maintained at 6 months. CONCLUSION: After 4
      weeks' use, wrist splints reduce pain, improve strength, and do not compromise
      dexterity. Similar improvements were achieved with the custom leather splint and
      Rolyan commercial splint, which were superior to the Anatech commercial splint.

PMID- 15478159
TI  - Comprehensive assessment of clinical outcome and quality of life after total
      shoulder arthroplasty: usefulness and validity of subjective outcome measures.
AB  - OBJECTIVE: To explore the physiometric and psychometric properties of clinical,
      generic, and condition-specific assessment instruments. To describe patients'
      outcome after total shoulder arthroplasty. METHODS: Forty-three patients were
      assessed in a 5-6-year cross-sectional catamnesis. RESULTS: With regard to
      shoulder joint stability, pain, general physical health, and mental health, the
      patients showed scores comparative to normative scores. Significant functional
      limitation was evidenced by low mean scores on the specific function scales
      (e.g., Disability of the Arm, Shoulder and Hand questionnaire score = 64.0,
      normative score = 86.6). There were high correlations among the joint-specific
      scales (up to 0.93) and moderate correlations between these and the generic and
      clinical scales. Factor analysis identified 3 different assessment domains.
      CONCLUSION: The patients' quality of life (QOL) was high and not affected by
      impairment in some specific functional abilities. Physical QOL, mental QOL,
      clinical assessment, condition-specific measures, and generic measures were
      identified as separate domains, all of which are required for a comprehensive and
      sophisticated assessment in practical clinical routine.

PMID- 15478160
TI  - Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in
      knee osteoarthritis.
AB  - OBJECTIVE: To assess the efficacy of glucosamine sulfate in knee osteoarthritis
      (OA). METHODS: A 4-center, 6-month, randomized, double-blind, placebo-controlled
      glucosamine discontinuation trial was conducted in 137 current users of
      glucosamine with knee OA who had experienced at least moderate improvement in
      knee pain after starting glucosamine. Study medication dosage was equivalent to
      the dosage of glucosamine taken prior to the study (maximum 1,500 mg/day).
      Followup continued for 6 months or until disease flare, whichever occurred first.
      The primary outcome was the proportion of disease flares in the glucosamine and
      placebo groups using an intent-to-treat analysis. Secondary outcomes included
      time to disease flare; analgesic medication use; severity of disease flare; and
      change in pain, stiffness, function and quality of life in the glucosamine and
      placebo groups. RESULTS: Disease flare was seen in 28 (42%) of 66 placebo
      patients and 32 (45%) of 71 glucosamine patients (difference -3%; 95% confidence
      interval [95% CI] -19, 14; P = 0.76). In the Cox regression analysis, after
      adjustment for sex, study site, and OA radiographic severity, time to disease
      flare was not significantly different in the glucosamine compared with placebo
      group (hazard ratio of flare = 0.8; 95% CI 0.5, 1.4; P = 0.45). At final study
      visit, acetaminophen was used in 27% and 21% of placebo and glucosamine patients,
      respectively (P = 0.40), nonsteroidal antiinflammatory drugs were used in 29% and
      30% (P = 0.92), and both were used in 20% and 21% (P = 0.84). No differences were
      found in severity of disease flare or other secondary outcomes between placebo
      and glucosamine patients. CONCLUSION: In patients with knee OA with at least
      moderate subjective improvement with prior glucosamine use, this study provides
      no evidence of symptomatic benefit from continued use of glucosamine sulfate.

PMID- 15478161
TI  - Patient-reported health care utilization in rheumatoid arthritis: what level of
      detail is required?
AB  - OBJECTIVE: To investigate the level of detail required in self-reported health
      care utilization questionnaires for administration to patients with rheumatoid
      arthritis (RA). METHODS: A preliminary questionnaire was developed on the basis
      of existing tools for use in rheumatic conditions and in-depth interviews with 10
      RA patients. Data gathered over 1 year of administration in a clinical setting
      were then matched to a comprehensive database of payer-reported information.
      Kappa statistics were calculated for each health care utilization domain. For
      domains where disaggregation into metric data was potentially preferable,
      histograms of difference were assessed visually and the strength of association
      examined using Spearman's rank correlation coefficient. RESULTS: Patients (n =
      136) included in the base case analysis determined the preferred levels of detail
      for each domain. Physician visits: occurrence of physician visits (yes/no; kappa
      not applicable) and their number (r = 0.42, P < 0.001). Medication use of the
      following drug classes (yes/no): disease-modifying antirheumatic drug (DMARD;
      kappa = 0.68), nonsteroidal antiinflammatory drug (kappa = 0.64), osteoporosis
      medication (kappa = 0.56), analgesic (kappa = 0.38), and steroid (kappa = 0.83).
      Further disaggregation into different DMARD classes was recommended (kappa
      ranging between 1 [use of biologics: yes/no] and 0.67 [use of azathioprine:
      yes/no]. Imaging: imaging of bones and chest (yes/no; kappa = 0.20).
      Hospitalization: inpatient episodes (yes/no; kappa = 0.64) and number of
      inpatient days (r = 0.80, P < 0.001). Transport: costs incurred (yes/no; kappa =
      0.13) and amount (r = 0.39, P < 0.001). CONCLUSION: The use of highly aggregated
      items to assess health care utilization in RA is supported. Dichotomous
      assessment (yes/no) was the preferred level of detail for items in the domains
      covering medication and diagnostic procedures or tests. Metric data is
      appropriate in 3 areas: number of physician visits, number of inpatient days, and
      total expenditure on transportation.

PMID- 15478162
TI  - Identification of modifiable work-related factors that influence the risk of work
      disability in rheumatoid arthritis.
AB  - OBJECTIVE: To define work-related factors associated with increased risk of work
      disability (WD) in people with rheumatoid arthritis (RA). METHODS: Questionnaires
      were mailed to all RA patients who used a province-wide arthritis treatment
      program between 1991 and 1998 (n = 1,824). The association between risk factors
      and WD (defined as no paid work due to RA for at least 6 months) was assessed
      using multiple logistic regression analysis, controlling for significant
      sociodemographic and disease-related variables. RESULTS: Of the original 1,824
      patients, 581 were eligible and responded to the questionnaire. Work survival
      analysis revealed a steady rate of WD starting early, with 7.5%, 18%, and 27%
      work disabled at 1, 5, and 10 years, respectively. Significant determinants in
      multiple logistic regression were physical function (Health Assessment
      Questionnaire), pain (visual analog scale), and 6 work-related factors: self
      employment, workstation modification, work importance, family support toward
      employment, commuting difficulty, and comfort telling coworkers about RA.
      CONCLUSION: Work disability occurs early in RA. Novel work-related factors were
      identified, which are potentially modifiable, to help RA patients stay employed.

PMID- 15478164
TI  - Are there more than cross-sectional relationships of social support and support
      networks with functional limitations and psychological distress in early
      rheumatoid arthritis? the European Research on Incapacitating Diseases and Social
      Support Longitudinal Study.
AB  - OBJECTIVE: To investigate whether greater social support and support network are
      cross-sectionally associated with less functional limitations and psychological
      distress in patients with early rheumatoid arthritis (RA); whether this
      association is constant over time; and whether increases in social support or
      support network are associated with less functional limitations and psychological
      distress. METHODS: Subjects were from the European Research on Incapacitating
      Diseases and Social Support cohort and had early RA. Social support, support
      network, functional limitations (Health Assessment Questionnaire), and
      psychological distress (General Health Questionnaire) were assessed annually.
      Variance and covariance analyses with repeated measures were performed. RESULTS:
      A total of 542 subjects were assessed for 3 years. On average, patients with a
      greater amount of specific social support or a stronger specific support network
      experienced less functional limitation and less psychological distress. Changes
      in a given subject's functional limitations and psychological distress did not
      depend on his or her baseline social support or support network. Neither social
      support nor support network change over time. CONCLUSION: There may be a cross
      sectional link between specific social support or support network and functional
      limitations and psychological distress, but no longitudinal association could be
      evidenced.

PMID- 15478165
TI  - Anti-tumor necrosis factor agents for rheumatoid arthritis in the setting of
      chronic hepatitis C infection.
AB  - OBJECTIVE: To examine the safety of using anti-tumor necrosis factor (TNF)
      therapy in patients with rheumatoid arthritis (RA) in the setting of hepatitis C
      virus (HCV) infection. METHODS: The charts of 5 patients known to have RA
      requiring anti-TNF therapy as well as established HCV infection were reviewed
      retrospectively for laboratory data of hepatic parenchymal inflammation and viral
      proliferation while taking these agents. RESULTS: In a mean +/- SD followup
      period of 41 months (+/- 28.2 months), no patient displayed evidence of sustained
      elevation of serum aminotransferases during therapy with anti-TNF. Additionally,
      1 patient was observed to have a decreased HCV viral load after extended
      treatment with only anti-TNF (no therapy for HCV). CONCLUSION: Anti-TNF therapy
      for RA in the setting of HCV appears to be safe and well tolerated without
      apparent influence on the underlying HCV infection. Therefore, this approach
      should be further evaluated prospectively for longterm safety.

PMID- 15478166
TI  - Pilot study of the effects of a heat-retaining knee sleeve on joint pain,
      stiffness, and function in patients with knee osteoarthritis.
AB  - OBJECTIVE: To identify changes in joint pain, stiffness, and functional ability
      in patients with knee osteoarthritis (OA) after use of a knee sleeve that
      prevents loss of body heat by the joint. METHODS: Subjects with symptomatic knee
      OA (n = 52) were randomized to 2 treatment groups: verum sleeve (specially
      fabricated to retain body heat) or placebo sleeve (standard cotton/elastane
      sleeve). Subjects wore the sleeve over the more painful OA knee for at least 12
      hours daily for 4 weeks. Pain, stiffness, and functional impairment (Western
      Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) in the index knee
      were measured at baseline and after 4 weeks of wear, after which sleeve use was
      discontinued. Telephone followup interviews were conducted 2 and 4 weeks later.
      RESULTS: After 4 weeks of sleeve wear, subjects in the active treatment group
      reported a 16% decrease in mean WOMAC pain score relative to baseline (P =
      0.001). Those who wore the placebo sleeve reported a 9.7% decrease from baseline
      (P = 0.002). The difference between treatment groups was not statistically
      significant (P = 0.12). However, it was found that the 12 subjects who believed
      correctly that they had received the verum sleeve reported a highly significant
      decrease in WOMAC pain score (-27.5% relative to baseline, P = 0.0001). In
      comparison, subjects who received the verum sleeve but believed they had received
      the placebo sleeve exhibited only a marginally significant improvement in pain (
      13.0% relative to baseline, P = 0.07). In the placebo group, the modest
      improvement in pain scores appeared unrelated to the subject's impression of the
      type of sleeve worn. CONCLUSION: This pilot study was insufficiently powered to
      be a definitive trial of the heat-retaining sleeve. Given the magnitude of
      changes in knee pain in the active treatment group, heat retention merits further
      scientific investigation as a treatment modality for patients with knee OA.

PMID- 15478167
TI  - A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents
      versus acetaminophen in the treatment of osteoarthritis: a meta-analysis.
AB  - OBJECTIVE: To perform a meta-analysis comparing the efficacy and safety of
      recommended dosages of nonsteroidal antiinflammatory drugs (NSAIDs), including
      cyclooxygenase 2 inhibitors, versus acetaminophen in the treatment of symptomatic
      hip and knee osteoarthritis. METHODS: Medline and EMBASE searches were performed
      for original clinical trials directly comparing NSAIDs with acetaminophen. A
      standardized form was used to abstract all data, including outcome measures of
      pain at rest, walking pain, and dropouts due to adverse effects. Inverse-variance
      weighted mean differences (WMDs) and 95% confidence intervals (95% CI) for pain
      measures were determined for treatment groups. Odds ratios (ORs) and 95% CIs were
      calculated for withdrawals due to adverse events. Results were compared using a
      random effects model. RESULTS: Seven articles met inclusion criteria with
      sufficient data for analysis. Participants had a mean age of 61.1 years and 71.1%
      were women. Test of heterogeneity was not significant for either rest (P = 0.73)
      or walking (P = 0.76) pain. The scores for overall pain at rest (WMD -6.33 mm on
      a 100-mm visual analog scale [VAS], 95% CI -9.24, -3.41) and walking pain (WMD 
      5.76 mm on a 100-mm VAS, 95% CI -8.99, -2.52) favored the NSAID-treated group.
      Although NSAIDs elevated the risk of withdrawals due to adverse events, the
      difference was not statistically significant (OR 1.45, 95% CI 0.93, 2.27).
      CONCLUSION: NSAIDs are statistically superior in reducing rest and walking pain
      compared with acetaminophen for symptomatic osteoarthritis. Safety, measured by
      discontinuation due to adverse events, was not statistically different between
      NSAID- and acetaminophen-treated groups.

PMID- 15478168
TI  - Sex effects on heart rate variability in fibromyalgia and Gulf War illness.
AB  - OBJECTIVE: To investigate autonomic abnormalities in male and female fibromyalgia
      (FM) and Gulf War illness (GWI) patients by comparing heart rate variability
      (HRV) with that of age- and sex-matched healthy controls. METHODS: Subjects
      included 26 (19 women, 7 men) with FM, 11 (6 men, 5 women) with GWI, and 36 (18
      men,18 women) healthy controls. HRV was determined from Holter recordings
      obtained in the Clinical Research Center. Analysis of variance compared 24-hour,
      daytime, and nighttime HRV by sex within groups and by group within sex. RESULTS:
      In women with FM or GWI, HRV was significantly lower than in men with FM or GWI.
      HRV was similar in male and female controls. When HRV was compared by group
      within sex, HRV was significantly decreased in women with FM or GWI and no
      significant differences were seen for men with these conditions. CONCLUSION:
      Decreased HRV in FM and GWI appears to be sex dependent. Results suggest that
      different mechanisms may be operative in symptom expression in men and women with
      this spectrum of illness.

PMID- 15478169
TI  - Norwegian version of the Canadian Occupational Performance Measure in patients
      with hand osteoarthritis: validity, responsiveness, and feasibility.
AB  - OBJECTIVE: To test the Norwegian version of the Canadian Occupational Performance
      Measure (COPM) for validity, responsiveness, and feasibility in patients with
      hand osteoarthritis. METHODS: Seventy-nine patients completed a COPM interview
      and several self-reported health status questionnaires, including Arthritis
      Impact Measurement Scales 2, modified Health Assessment Questionnaire; Western
      Ontario and McMaster Universities Osteoarthritis Index, and the
      Australian/Canadian Osteoarthritis Hand Index. Rescoring of the same instruments
      was performed 4 months later, after an intervention. RESULTS: The COPM detected a
      great variability of occupational performance problems. The hypotheses for
      testing validity were confirmed. Mean COPM change was 1.51 (P < 0.001) in
      performance score, and 2.22 (P < 0.001) in satisfaction score. The median time
      spent on the COPM interview was 30 minutes (range 10-70 minutes). The patients
      found the questions easy to understand, but 37% reported problems performing the
      scoring procedure. CONCLUSIONS: The Norwegian version of the COPM is a valid and
      responsive instrument for use in clinical practice in osteoarthritis patients. It
      may serve as an instrument to promote a client-centered approach and as a
      supplement to other health measures in the planning and evaluating of
      interventions. Feasibility regarding scoring needs to be improved.

PMID- 15478170
TI  - Use of a complex approach for assessment of metamizole sodium and acetylsalicylic
      acid toxicity, genotoxicity and cytotoxicity.
AB  - A complex approach based on the use of test organisms belonging to different
      systematic groups (plants, invertebrates and vertebrates), as well as the
      nucleolar biomarker and the micronucleus test on their cells, was applied to
      assess the toxicity, cytotoxicity and genotoxicity of two pharmaceutical
      substances (metamizole sodium and acetylsalicylic acid) applied at ic(50)
      concentrations for mammalian cells. The compound acetylsalicylic acid was
      evaluated at a concentration (1.6 x 10(3) mg l(-1)) that was non-toxic for
      bioassays based on fish (Carassius auratus gibelio) and hydra (Hydra attenuata)
      and acutely toxic for bioassays with ceriodaphnia (Ceriodaphnia affinis) and
      onion (Allium cepa). The metamizole sodium solution (6.25%) demonstrated acute
      toxicity for the whole set of test organisms. Both drugs, after their 30-360 min
      influence on the test organisms, first changed the nucleolar size in plant and
      animal cells (i.e. the transcriptional activity of ribosomal genes was affected
      most significantly). Moreover, the metamizole sodium solution caused nucleolar
      structural damage in 90% of hydra cells as early as after 30 min of exposure. The
      acetylsalicylic acid solution inhibited essentially the rate of cell division in
      the meristem of onion roots (the mitotic index decreased to 9.6 per thousand, as
      compared 51.7 per thousand for the control). The carp incubation and the onion
      germination in the acetylsalicylic acid solution showed a reproducible increase
      in the frequency of cells with micronuclei (2 and 5.5 times, respectively) and
      double nuclei (3 and 1.5 times, respectively). The approach described herein may
      be applied for obtaining rapid, cost-efficient and useful supplementary data on
      different types of toxicity for marketed drugs as well as for drugs under
      development.

PMID- 15478171
TI  - Response characteristics of an aquatic biomonitor used for rapid toxicity
      detection.
AB  - The response characteristics of an aquatic biomonitor that detects toxicity by
      monitoring changes in bluegill (Lepomis macrochirus Rafinesque) ventilatory and
      movement patterns were evaluated in single chemical laboratory studies at
      concentrations near the 96-h LC(50) concentration and at the EILATox-Oregon
      Workshop in sequential tests of multiple unknown samples. Baseline data collected
      prior to exposure allows each fish to serve as its own control. When at least 70%
      of exposed fish exhibit ventilatory or movement parameters significantly
      different from baseline observations, a group alarm is declared. In the
      laboratory studies, the aquatic biomonitor responded to the majority of chemicals
      at the 96-h lc(50) within an hour or less, although substantially higher response
      times were found for malathion and pentachlorophenol. Workshop tests of single
      chemical concentrations presented as blind samples were consistent with the
      laboratory test results. There were no alarms under control conditions in any
      test. Although data are limited, the aquatic biomonitor appears to respond more
      rapidly to chemicals causing membrane irritation, narcosis or polar narcosis than
      to acetylcholinesterase inhibitors or oxidative phosphorylation uncouplers. All
      four monitored parameters (ventilatory rate, cough rate, ventilatory depth and
      movement) contributed to identification of first alarms at acutely toxic levels.
      Understanding these response patterns can be useful in data interpretation for
      biomonitor applications such as surface water monitoring for watershed
      protection, wastewater treatment plant effluent monitoring or source water
      monitoring for drinking water protection.

PMID- 15478172
TI  - Monitoring genotoxicity during the photocatalytic degradation of p-nitrophenol.
AB  - p-Nitrophenol is a common structural unit of many pesticides and was chosen as a
      model compound to monitor genotoxicity during photocatalytic degradation. The
      genotoxicity of p-nitrophenol (PNP) and its breakdown products was measured using
      a bioluminescent bacterial bioassay, Vitotox. The genotoxic potential decreased
      with the concomitant photocatalytic degradation of the parent PNP concentration.
      The rate of genotoxicity reduction was slower than the rate of removal of the
      parent PNP, due to the formation of genotoxic by-products. After 6 h of
      photocatalytic treatment the total genotoxicity was removed. These results
      indicate that bioassays can be used as a simple and highly sensitive method for
      monitoring the general toxicity of chemical pollutants before, during and after
      photocatalytic treatment or other destructive processes.

PMID- 15478174
TI  - Cultured neuronal networks as environmental biosensors.
AB  - Contamination of water by toxins, either intentionally or unintentionally, is a
      growing concern for both military and civilian agencies and thus there is a need
      for systems capable of monitoring a wide range of natural and industrial
      toxicants. The EILATox-Oregon Workshop held in September 2002 provided an
      opportunity to test the capabilities of a prototype neuronal network-based
      biosensor with unknown contaminants in water samples. The biosensor is a portable
      device capable of recording the action potential activity from a network of
      mammalian neurons grown on glass microelectrode arrays. Changes in the action
      potential fi ring rate across the network are monitored to determine exposure to
      toxicants. A series of three neuronal networks derived from mice was used to test
      seven unknown samples. Two of these unknowns later were revealed to be blanks, to
      which the neuronal networks did not respond. Of the five remaining unknowns, a
      significant change in network activity was detected for four of the compounds at
      concentrations below a lethal level for humans: mercuric chloride, sodium
      arsenite, phosdrin and chlordimeform. These compounds--two heavy metals, an
      organophosphate and an insecticide--demonstrate the breadth of detection possible
      with neuronal networks. The results generated at the workshop show the promise of
      the neuronal network biosensor as an environmental detector but there is still
      considerable effort needed to produce a device suitable for routine environmental
      threat monitoring.

PMID- 15478173
TI  - Water toxicity detection by a panel of stress-responsive luminescent bacteria.
AB  - A panel of Escherichia coli strains harbouring different stress-responsive
      promoters fused to a lux reporter system was used to assess the potential
      toxicity of 17 unknown model water samples. Using liquid cultures, nine out of 14
      toxic samples were properly identified as toxic, whereas five were false
      negatives. All three non-toxic controls were identified correctly (no false
      positives). Two strains containing promoter-lux fusions were also tested when
      immobilized onto fibre-optic tips. One genotoxic sample and six toxic samples
      were correctly identified in this manner. The potential advantages and
      limitations in the use of genetically engineered bacteria as biosensors for water
      toxicity are discussed in view of these results.

PMID- 15478175
TI  - EILATox-Oregon Workshop: blind study evaluation of Vitotox test with genotoxic
      and cytotoxic sample library.
AB  - In order to assess the robustness, sensitivity and specificity of a recently
      developed Vitotox test, 17 blind coded chemicals and three environmental water
      samples were tested at the EILATox-Oregon Workshop using the Thermo Electron
      Vitotox kit. The Vitotox test is a rapid geno- and cytotoxicity test using
      standard 96- or 384-well microtitre plates. The genotoxicity test is based on two
      genetically modified Salmonella typhimurium strains containing bacterial
      luciferase operon from Vibrio fisheri under the SOS inducible promoter. The SOS
      system is an inducible network in Escherichia coli that responds to DNA damage
      and activates DNA repair. The Vitotox genotoxicity test bacteria strain carries
      bacterial luciferase genes under the control of SOS inducible promoter and
      therefore any DNA damage inside the cells induces the production of bacterial
      luciferase. The luciferase expression is then followed with a microtitre plate
      luminometer for 3 h after mixing different dilutions of sample with the test
      bacteria. The genotoxicity index is calculated for each dilution and the
      genotoxicity of the sample is interpreted based on kinetic time curves and
      genotoxicity vs concentration/dilution curves. Cytotoxicity of the sample is
      determined simultaneously with another test strain containing the same luciferase
      operon controlled by the constitutive promoter. This bacterium produces constant
      bioluminescence and any decrease of the bioluminescence production is used as a
      marker for cytotoxicity. As a miniaturized microtitre plate assay the Vitotox
      test requires a very small quantity of the sample material. The samples used in
      the workshop were diluted 1 : 10 or 1 : 100 before testing. Genotoxicity and
      cytotoxicity data were collected at dilutions of 1 : 10-1 : 2000. When the
      samples of the EILATox-Oregon Workshop were tested using the Vitotox test, four
      coded chemicals out of 17 were determined to be genotoxic. Seven chemicals and
      one environmental sample were found to be cytotoxic. Three chemical samples were
      found to be both geno- and cytotoxic.

PMID- 15478176
TI  - Detection of bioavailable heavy metals in EILATox-Oregon samples using whole-cell
      luminescent bacterial sensors in suspension or immobilized onto fibre-optic tips.
AB  - At the EILATox-Oregon Workshop, nine luminescent whole-cell bacterial sensors
      were used for the determination of bioavailable metals in blind samples (17
      synthetic and 3 environmental). A non-inducible luminescent control strain was
      used to determine sample matrix effects and bacterial toxicity. Whole-cell
      bacterial sensors capable of determining arsenic, inorganic mercury and its
      organic derivatives, cadmium, lead or copper were used in suspensions and a
      bacterial sensor for the detection of inorganic mercury was immobilized onto
      fibre-optic tips using calcium alginate. Bioavailable amounts of metals were
      estimated using calibration plots, that were constructed to determine the range
      of metals giving rise to a linear relationship between luminescence and the
      amount of metals present in the standard solutions. EILATox-Oregon sample 5,
      which contained 74 mg l(-1) of Hg, gave a significant response with both formats
      of the mercury sensor. The bioavailable amounts of mercury according to the
      measurement of bacterial sensor in suspension and immobilized onto a fibre-optic
      tip were 76 and 93 mg l(-1), respectively. The bacterial sensor for arsenic and
      copper showed a response with sample 6 (58 mg l(-1) of As) and sample 8 (400 mg
      l(-1) of metham sodium), respectively. This study showed that the bacterial
      sensors in suspension or immobilized onto optical fibres are capable of
      quantifying bioavailable metals from unknown samples. The measurement protocol of
      bacterial sensors is simple and possible to perform in the field. Moreover, the
      samples do not need any pretreatment before analysis. Construction and
      characterization of the strain for the detection of bioavailable copper are
      described.

PMID- 15478177
TI  - Sensitivity evaluation of the Daphtoxkit and Thamnotoxkit microbiotests on blind
      samples.
AB  - At the Oregon State University Workshop we utilized two "culture/maintenance
      free" microbiotests, the Thamnotoxkit F with the anostracan crustacean
      Thamnocephalus platyurus and the Daphtoxkit F magna with the cladoceran
      crustacean Daphnia magna, to determine the toxicity of water samples in a blind
      format. The Thamnotoxkit was applied to 7 samples and the Daphtoxkit to 12
      samples. The chemical composition of the water samples to which the Toxkit
      microbiotests had been applied was disclosed a posteriori by the organizers and
      appeared to contain chlordimeform, colchicine, phosdrin, mercuric chloride,
      sodium arsenite, metham sodium, sodium cyanide, trimethylol propane phosphate, p
      chlorophenol and a natural sediment sample containing mercury. Three of the water
      samples were blanks that had not been spiked with chemicals. No false positives
      were obtained with the two Toxkits and all the toxic waters were earmarked as
      such by the microbiotests, except trimethylol propane phosphate, which was not
      found to induce acute effects in Daphnia magna in the non-diluted water sample
      containing 100 mg l(-1) of this compound.

PMID- 15478178
TI  - (-)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial
      activation and protects against inflammation-mediated dopaminergic neuronal
      injury.
AB  - Microglial activation is believed to play a pivotal role in the selective
      neuronal injury associated with several neurodegenerative disorders, including
      Parkinson's disease (PD) and Alzheimer's disease. We provide evidence that (-)
      epigallocatechin gallate (EGCG), a major monomer of green tea polyphenols,
      potently inhibits lipopolysaccharide (LPS)-activated microglial secretion of
      nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) through the down
      regulation of inducible NO synthase and TNF-alpha expression. In addition, EGCG
      exerted significant protection against microglial activation-induced neuronal
      injury both in the human dopaminergic cell line SH-SY5Y and in primary rat
      mesencephalic cultures. Our study demonstrates that EGCG is a potent inhibitor of
      microglial activation and thus is a useful candidate for a therapeutic approach
      to alleviating microglia-mediated dopaminergic neuronal injury in PD.

PMID- 15478180
TI  - Effects of Ganoderma lucidum on apoptotic and anti-inflammatory function in HT-29
      human colonic carcinoma cells.
AB  - Ling Zhi extract (LZE) is a herbal mushroom preparation which been used world
      wide for the prevention and treatment of various cancers. The current study was
      designed to evaluate these claims in human colon cancer cells in terms of cancer
      preventive mechanisms. Results have demonstrated induction of apoptosis, anti
      inflammatory action and differential cytokine expression during induced
      inflammation in the human colonic carcinoma cell line, HT-29. LZE caused no
      cytotoxicity in HT-29 cells at doses less than 10,000 microg/ml. Increasing
      concentrations of LZE reduced prostaglandin E2 production, but increased nitric
      oxide production. LZE treatment induced apoptosis by increasing the activity of
      caspase-3. RT-PCR showed that LZE at a concentration of 5000 microg/ml decreased
      the expression of cyclooxygenase-2 mRNA. Among 42 cytokines tested by protein
      array in this study, supplementation of LZE at doses of 500 and 5000 microg/ml to
      HT-29 cells reduced the expression of interleukin-8, macrophage inflammatory
      protein 1-delta, vascular epithelial growth factor, and platelet-derived growth
      factor. These results suggest that LZE has pro-apoptotic and anti-inflammatory
      functions, as well as inhibitory effects on cytokine expression during early
      inflammation in colonic carcinoma cells, which may be of significance in the use
      of Chinese herbal alternative medicines for cancer prevention.

PMID- 15478179
TI  - Tumor necrosis factor-alpha and alphaB-crystallin up-regulation during antibody
      mediated demyelination in vitro: a putative protective mechanism in
      oligodendrocytes.
AB  - By using an in vitro model of antibody-mediated demyelination, we investigated
      the relationship between tumor necrosis factor-alpha (TNF-alpha) and heat shock
      protein (HSP) induction with respect to oligodendrocyte survival. Differentiated
      aggregate cultures of rat telencephalon were subjected to demyelination by
      exposure to antibodies against myelin oligodendrocyte glycoprotein (MOG) and
      complement. Cultures were analyzed 48 hr after exposure. Myelin basic protein
      (MBP) expression was greatly decreased, but no evidence was found for either
      necrosis or apoptosis. TNF-alpha was significantly up-regulated. It was localized
      predominantly in neurons and to a lesser extent in astrocytes and
      oligodendrocytes, and it was not detectable in microglial cells. Among the
      different HSPs examined, HSP32 and alphaB-crystallin were up-regulated; they may
      confer protection from oxidative stress and from apoptotic death, respectively.
      These results suggest that TNF-alpha, often regarded as a promoter of
      oligodendroglial death, could alternatively mediate a protective pathway through
      alphaB-crystallin up-regulation.

PMID- 15478181
TI  - Identification of antioxidant compound from Asparagus racemosus.
AB  - Roots of Asparagus racemosus were found to possess antioxidant property. DPPH
      autography-directed separation resulted in the identification of a new
      antioxidant compound named racemofuran (3) along with two known compounds
      asparagamine A (1) and racemosol (2). The structure of 3 was fully characterized
      by spectroscopic data (UV, MS, 1H NMR, 13C NMR, and 2D NMR). Racemofuran revealed
      antioxidant property against DPPH with IC50 value of 130 microM.

PMID- 15478182
TI  - Responses of fish chromatophore-based cytosensor to a broad range of biological
      agents.
AB  - A cytosensor based on living chromatophores from Betta splendens Siamese fighting
      fish was used to test several classes of biologically active agents. Tested
      agents include neurotransmitters, adenyl cyclase activators, cytoskeleton
      effectors, cell membrane effectors and protein synthesis inhibitors.
      Characteristic cell responses were analyzed, and potential cytosensor
      applications were considered. Streptococcus pyogenes toxins streptolysin S and
      streptolysin O, Clostridium tetani tetanolysin, Staphylococcus aureus alpha-toxin
      and Vibrio parahemolyticus hemolysin, all bacterial toxins that act on cell
      membranes, elicited a strong response from chromatophores. A comparison of
      purified toxin to actual bacterial culture from Vibrio parahemolyticus
      demonstrated a nearly identical chromatophore cell response pattern. This
      suggests that the cytosensor response is reflective of bacterial toxin
      production.

PMID- 15478183
TI  - Detection and classification of threat agents via high-content assays of
      mammalian cells.
AB  - One property common to all chemical or biological threat agents is that they
      damage mammalian cells. A threat detection and classification method based on the
      effects of compounds on cells has been developed. This method employs high
      content screening (HCS), a concept in drug discovery that enables those who
      practice cell-based assays to generate deeper biological information about the
      compounds they are testing. A commercial image-based cell screening platform
      comprising fluorescent reagents, automated image acquisition hardware, image
      analysis algorithms, data management and informatics was used to develop assays
      and detection/classification methods for threat agents. These assays measure a
      cell's response to a compound, which may include activation or inhibition of
      signal transduction pathways, morphological changes or cytotoxic effects. Data on
      cell responses to a library of compounds was collected and used as a training
      set. At the EILATox-Oregon Workshop, cellular responses following exposure to
      unknown samples were measured by conducting assays of p38 MAP kinase, NF-kappaB,
      extracellular-signal related kinase (ERK) MAP kinase, cyclic AMP-response element
      binding protein (CREB), cell permeability, lysosomal mass and nuclear morphology.
      Although the assays appeared to perform well, only four of the nine toxic samples
      were detected. However the system was specific, because no false positives were
      detected. Opportunities for improvement to the system were identified during the
      course of this enlightening workshop. Some of these improvements were applied in
      subsequent tests in the Cellomics laboratories, resulting in a higher level of
      detection. Thus, an HCS approach was shown to have potential in detecting threat
      agents, but additional work is necessary to make this a comprehensive detection
      and classification system.

PMID- 15478184
TI  - EILATox-Oregon Biomonitoring Workshop: summary and observations.

PMID- 15478185
TI  - Blind and naive classification of toxicity by fish chromatophores.
AB  - Cellular and molecular pathways involved in the ability of animals to change
      color have been studied previously as biosensors and cytosensors of active and
      toxic agents, but such studies generally have been limited to just a few
      standardized agents. Here we describe the performance of cultured chromatophore
      pigment cells from the fin tissue of Siamese fighting fish as sensors of toxic
      agents under blind sampling conditions at the September 2002 EILATox-Oregon
      Workshop. Detection was accomplished by monitoring motor protein-mediated
      movements of cellular pigment in chromatophores at both the gross population
      level as well as in singly imaged cells. Pigment responses were recorded both
      during the exposure of chromatophores to each blind sample as well as afterwards
      when the cells were examined for after-effects by challenging them with
      clonidine, an adrenergic drug that induces standardized pigment movements. After
      recording all results and upon breaking the key to reveal the identities of the
      toxic agents, it was found that all of the toxic samples in the study had been
      distinguished accurately from non-toxic controls that were included among the
      blind samples. Furthermore, it was revealed that most of the toxic agents
      detected had never before been tested or calibrated against chromatophores,
      demonstrating that detection can be achieved under naive conditions that have not
      been optimized for the analysis of any particular toxic agent. Finally, by
      organizing the results into categories of pigment responses, a binary
      classification tree was generated that distinguished each toxic agent as having a
      distinct response pattern from the others. Thus, chromatophore-based cytosensors
      can discover toxicity in the absence of prior knowledge of the agent in question,
      and the categories of responses of the cells can be used to distinguish one toxic
      agent from another.

PMID- 15478187
TI  - Developing advanced toxicology technologies for biomonitoring in national
      security applications.

PMID- 15478188
TI  - Antimicrobial activity of tiger's betel (Piper porphyrophyllum N.E. Br.,
      Piperaceae).
AB  - The ethanol extract of leaves of Piper porphyrophyllum N.E. Br. showed a broad
      spectrum of antibacterial activity. The activity was increased on fractionation
      (hexane, dichloromethane and aqueous), particularly in the aqueous fraction. No
      activity was shown against tested Candida albicans.

PMID- 15478189
TI  - Restoration of antioxidant defence by ethanolic Tinospora cordifolia root extract
      in alloxan-induced diabetic liver and kidney.
AB  - The present study investigates the effect of oral administration of an alcoholic
      extract of Tinospora cordifolia roots on antioxidant defence in alloxan-induced
      diabetes in rats. A significant increase in the concentration of thiobarbituric
      acid reactive substances (TBARS) in liver and kidney was observed in diabetic
      rats. Decreased concentration of glutathione (GSH) and decreased activities of
      superoxide dismutase (SOD), and catalase in liver and kidney of diabetic rats
      were also noted. Alcoholic Tinospora cordifolia root extract (TCREt) administered
      at a dose of 100 mg/kg body weight to diabetic rats orally for six weeks
      normalized the antioxidant status of liver and kidney. The effect of Tinospora
      cordifolia root extract was more potent than glibenclamide (600 microg/kg body
      weight). Insulin (6 units/kg) restored all the parameters to normal status.

PMID- 15478190
TI  - Evaluation of antitussive activity of Lagerstroemia parviflora leaf extract.
AB  - The methanol extract of the leaves of Lagerstroemia parviflora Roxb was
      investigated for its effect on a cough model induced by sulfur dioxide gas in
      mice. It exhibited significant antitussive activity when compared with the
      control in a dose-dependent manner. The L. parviflora extract (100, 200, 300
      mg/kg) showed maximum inhibition of cough reflex at 90 min after drug
      administration and the antitussive activity was comparable to that of codeine
      phosphate, a standard antitussive agent.

PMID- 15478192
TI  - Effect of age on the duration and extent of amyloid plaque reduction and
      microglial activation after injection of anti-Abeta antibody into the third
      ventricle of TgCRND8 mice.
AB  - We have previously shown that anti beta-amyloid (Abeta) antibody injected into
      the third ventricle of mice is distributed throughout the brain within 24 hr and
      is completely washed out of brain within 36 hr after injection and that, in
      Tg2576 animals, a single injection of antibody reduces cerebral Abeta and
      restores presynaptic deficits 1 month after injection without producing
      hemorrhage or inflammation at an early plaque stage. Here we report the effects
      of a single ICV injection of anti-Abeta antibody on cerebral levels of
      immunoreactive Abeta and of microglial activation measured by immunoreactive
      interleukin-1beta (IL-1beta) at 1, 4, and 8 weeks after injections in TgCRND8
      mice at two ages, 2 months (sparse plaques) and 8 months (abundant plaques). The
      data show that parenchymal amyloid accumulates before cerebral microvascular
      amyloid and that a single ICV injection reduces only parenchymal amyloid by about
      70%, without affecting vascular amyloid, and reduces microglial activation by 46
      60% at 1 week after injection. The reappearance of plaques after antibody
      injection takes 4-8 weeks, whereas plaque-associated focal microglial activation
      begins increasing between 1 and 4 weeks, suggesting that accumulation of
      nonfibrillar oligomeric Abeta may account for the earlier onset of microglial
      activation. No perivascular hemorrhage or inflammation was observed. These
      results suggest that periodic intraventricular administration of anti-Abeta is a
      potentially useful method for rapid reduction of both preexisting amyloid load
      and associated inflammation, providing a window of 4 weeks' duration for possible
      pharmacological cotreatment(s) to prevent de novo Abeta formation. This ICV
      method of passive immunization may be safer than active immunization, which has
      been known to produce encephalitis, or systemic passive immunization, which
      exposes amyloid-laden cerebral microvasculature to high levels of antibody in the
      blood and the potential of perivascular hemorrhages.

PMID- 15478191
TI  - Neuroprotective effect of activity-dependent neurotrophic factor against toxicity
      from familial amyotrophic lateral sclerosis-linked mutant SOD1 in vitro and in
      vivo.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common fatal motor neuron
      disease, affecting mostly middle-aged people. There are no curative therapies for
      ALS. Several lines of evidence have supported the notion that the proapoptotic
      property of familial ALS (FALS)-linked mutant Cu/Zn-superoxide dismutase-1 (SOD1)
      genes may play an important role in the pathogenesis of some FALS cases. Here we
      found that activity-dependent neurotrophic factor (ADNF), a neurotrophic factor
      originally identified to have the anti-Alzheimer's disease (AD) activity,
      protected against neuronal cell death caused by FALS-linked A4T-, G85R- and G93R
      SOD1 in a dose-responsive fashion. Notably, ADNF-mediated complete suppression of
      SOD1 mutant-induced neuronal cell death occurs at concentrations as low as 100
      fM. ADNF maintains the neuroprotective activity even at concentrations of more
      than 1 nM. This is in clear contrast to the previous finding that ADNF loses its
      protective activity against neurotoxicity induced by AD-relevant insults,
      including some familial AD genes and amyloid beta peptide at concentrations of
      more than 1 nM. Characterization of the neuroprotective activity of ADNF against
      cell death caused by SOD1 mutants revealed that CaMKIV and certain tyrosine
      kinases are involved in ADNF-mediated neuroprotection. Moreover, in vivo studies
      showed that intracerebroventricularly administered ADNF significantly improved
      motor performance of G93A-SOD1 transgenic mice, a widely used model of FALS,
      although survival was extended only marginally. Thus, the neuroprotective
      activity of ADNF provides a novel insight into the development of curative drugs
      for ALS.

PMID- 15478193
TI  - Antibacterial and antifungal activity of Senecio inaequidens DC. and Senecio
      vulgaris L.
AB  - The antibacterial and antifungal activities of methanol extract, ethyl acetate,
      dichloromethane, n-hexane, n-butanol and chloroform fractions of Senecio
      inaequidens DC. and Senecio vulgaris L. were assayed. The hexane extract of
      Senecio vulgaris L. (MIC 0.031 mg/ml) showed significant activity against
      Trichophyton tonsurans.

PMID- 15478194
TI  - A multicenter study of supportive-expressive group therapy for women with
      BRCA1/BRCA2 mutations.
AB  - BACKGROUND: Women with a BRCA1/BRCA2 mutation experience significant challenges.
      These include decision-making regarding surgical options and notification to
      offspring and family, along with a sense of isolation, which may lead to
      psychological and emotional distress. The current study developed, standardized,
      and conducted preliminary testing of a supportive-expressive group therapy
      intervention designed to address these challenges. METHODS: Seventy women with a
      BRCA1/BRCA2 mutation recruited from familial cancer risk clinics participated in
      12 sessions of supportive-expressive group therapy that lasted 6 months. Before
      and after measures of psychosocial functioning, knowledge, and
      surveillance/surgery activities were completed. RESULTS: Sixty-seven women
      completed the intervention. Significant improvements were observed in
      psychosocial functioning: cancer worries (P = 0.005), anxiety (P = 0.033), and
      depression (P = 0.015). Knowledge level and surveillance levels were high at
      baseline and there were no significant changes postintervention. A significant
      number of women made decisions concerning prophylactic surgery
      (oophorectomy/mastectomy) during and after the intervention. CONCLUSIONS: The
      feasibility of a supportive-expressive group for BRCA1/BRCA2 mutation carriers
      was demonstrated. Findings from the study are consistent with an effective
      intervention. However, further research is required using a randomized controlled
      study design.

PMID- 15478195
TI  - Analysis of K+ accumulation reveals privileged extracellular region in the
      vicinity of glial cells in situ.
AB  - Astrocytes and oligodendrocytes in rat and mouse spinal cord slices,
      characterized by passive membrane currents during de- and hyperpolarizing
      stimulation pulses, express a high resting K+ conductance. In contrast to the
      case for astrocytes, a depolarizing prepulse in oligodendrocytes produces a
      significant shift of reversal potential (Vrev) to positive values, arising from
      the larger accumulation of K+ in the vicinity of the oligodendrocyte membrane. As
      a result, oligodendrocytes express large tail currents (Itail) after a
      depolarizing prepulse due to the shift of K+ into the cell. In the present study,
      we used a mathematical model to calculate the volume of the extracellular space
      (ECS) in the vicinity of astrocytes and oligodendrocytes (ESVv), defined as the
      volume available for K+ accumulation during membrane depolarization. A
      mathematical analysis of membrane currents revealed no differences between glial
      cells from mouse (n = 59) or rat (n = 60) spinal cord slices. We found that the
      Vrev of a cell after a depolarizing pulse increases with increasing Itail,
      expressed as the ratio of the integral inward current (Qin) after the
      depolarizing pulse to the total integral outward current (Qout) during the pulse.
      In astrocytes with small Itail and Vrev ranging from -50 to -70 mV, the Qin was
      only 3-19% of Qout, whereas, in oligodendrocytes with large Itail and Vrev
      between -20 and 0 mV, Qin/Qout was 30-75%. On the other hand, ESVv decreased with
      increasing values of Vrev. In astrocytes, ESVv ranged from 2 to 50 microm3, and,
      in oligodendrocytes, it ranged from 0.1 to 2.0 microm3. Cell swelling evoked by
      the application of hypotonic solution shifted Vrev to more positive values by
      17.2 +/- 1.8 mV and was accompanied by a decrease in ESVv of 3.6 +/- 1.3 microm3.
      Our mathematical analysis reveals a 10-100 times smaller region of the
      extracellular space available for K+ accumulation during cell depolarization in
      the vicinity of oligodendrocytes than in the vicinity of astrocytes. The presence
      of such privileged regions around cells in the CNS may affect the accumulation
      and diffusion of other neuroactive substances and alter communication between
      cells in the CNS.

PMID- 15478196
TI  - Pharmacological activities of some Argyranthemum species growing in the Canary
      Islands.
AB  - Methanolic extracts of eight subspecies of genus Argyranthemum were evaluated
      against brine shrimps, human cancer cell lines, malarial parasites and
      microorganisms under in vitro conditions. In the shrimp assay, samples of A.
      adauctum ssp. adauctum, A. adauctum ssp. erythrocarpon and A. frutetescens ssp.
      succulentum were active with ED50 values in the range of around 300 to 360
      microg/ml. In the Caco-2, HepG2 and MCF-7 cell lines, the samples A. adauctum
      ssp. jacobaeifolium and A. adauctum ssp. palmensis were active with LC50 values
      ranging between 80-90 microg/ml. The secondary assay results of antimalarial
      activity of samples, A. adauctum ssp. adauctum, A. adauctum ssp. dugourii, A.
      adauctum ssp. erythrocarpon and A. adauctum ssp. jacobaeifolium have IC50 values
      <50 microg/ml. The samples demonstrated broad specific antimicrobial activity
      against five different microorganisms.

PMID- 15478197
TI  - The antimycobacterial components of hops (Humulus lupulus) and their
      dereplication.
AB  - Bioassay-guided fractionation of a hexane extract of strobile hops (Humulus
      lupulus) was undertaken to isolate and characterize the antimycobacterial
      constituents using the fast-growing mycobacterial species Mycobacterium
      fortuitum. Activity was associated with a low polarity fraction and 1H NMR
      spectra indicated the presence of a fatty acid mixture with unsaturated
      components. GC-MS of the derivatives indicated the presence of palmitic, stearic
      and oleic acids with small quantities of lignoceric, arachidic, behenic and
      linoleic acids. These compounds were assessed against M. fortuitum and all
      saturated fatty acids were inactive at concentrations greater than 256 microg/ml,
      whereas the unsaturated fats oleic and linoleic acids displayed minimum
      inhibitory concentrations of between 4 and 16 microg/ml against the fast-growing
      species tested. The widespread occurrence of these components could render
      screening for antimycobacterials from natural sources highly problematic without
      adequate dereplication. We propose that GC-MS of derivatised components of
      lipophilic extracts be a first step before any antimycobacterial bioassay-guided
      study, as this technique is the method of choice for dereplication of fatty
      acids.

PMID- 15478198
TI  - Antibacterial activity of volatile component and various extracts of Spirulina
      platensis.
AB  - The methanol, dichloromethane, petroleum ether, ethyl acetate extracts and
      volatile components of Spirulina platensis were tested in vitro for their
      antimicrobial activity (four Gram-positive, six Gram-negative bacteria and
      Candida albicans ATCC 10239). GC-MS analysis of the volatile components of S.
      platensis resulted in the identification of 15 compounds which constituted 96.45%
      of the total compounds. The volatile components of S. platensis consisted of
      heptadecane (39.70%) and tetradecane (34.61%) as major components. The methanol
      extract showed more potent antimicrobial activity than dichloromethane, petroleum
      ether, ethyl acetate extracts and volatile components.

PMID- 15478199
TI  - Screening of wood damaging fungi and macrofungi for inhibitors of pancreatic
      lipase.
AB  - A total of 120 methanol and dichloromethane extracts, from 60 species of wood
      damaging fungi and 50 methanol/water extracts from macrofungi were screened for
      inhibition of pancreatic lipase using the chromogenic substrate p
      nitrophenylpalmitate. Of the extracts screened, those from Laetiporus sulphureus,
      Tylopilus felleus and Hygrocybe conica exhibited the highest lipase inhibitory
      activities of 83% +/- 5%, 96% +/- 3% and 97% +/- 5%, respectively.

PMID- 15478200
TI  - Screening extracts of Madagascan plants in search of antiplasmodial compounds.
AB  - One hundred and ninety plants, of which 51 are used to treat malaria in
      traditional medicine, were collected in five different ecosystems of Madagascar
      for a screening programme devoted to the search of naturally-occurring
      antimalarial compounds. Thirty-nine plants, of which 12 are used as herbal
      antimalarials, were found to display in vitro activity against Plasmodium
      falciparum with a median inhibitory concentration (IC50) lower than 5 microg/ml
      while 9 had an IC50 ranging from 5 to 7.5 microg/ml. Seventeen of them exhibited
      cytotoxic effects on murine P388 leukemia cells with an IC50 < 10 microg/ml. The
      biological activities were mostly located in the ethyl acetate fractions.
      Bioassay-directed fractionation is underway to isolate the active constituents.

PMID- 15478201
TI  - Plants used by a Quilombola group in Brazil with potential central nervous system
      effects.
AB  - This study focused on an ethnopharmacological survey among a group of Brazilian
      Quilombolas (descended from runaway slaves living in hideouts up-country) whose
      therapeutic practices involve a combination of healing ceremonies and
      prescription of medicinal plants consisting of the use of, at least, 48 plants
      with possible effect on the central nervous system (CNS), cited in 53 formulas
      prescribed for 17 therapeutic indications, the main ones being: to fortify the
      brain, for insomnia, as a sedative, for insanity, weight loss, and rejuvenation.
      The formulas consist of one to ten plants, and each plant may be recommended for
      up to seven different therapeutic indications, with evidence of non-specificity
      in the use of plants in this culture. Of these 48 plants, only 31 could be
      identified to the species level as belonging to 20 taxonomic families, with the
      Asteraceae, Malpighiaceae, Cyperaceae, and Myrtaceae as the most important
      families. Only eleven of these species have been previously studied and appear in
      scientific literature. Some of these plants are at present under study in the
      Department of Psychobiology of the Federal University of Sao Paulo.

PMID- 15478202
TI  - Evaluation of bioactive saponins and triterpenoidal aglycons for their binding
      properties on human endothelin ETA and angiotensin AT1 receptors.
AB  - Different types of triterpenes including saponins and aglycons were evaluated for
      their ability to inhibit [3H] BQ-123 and [3H] angiotensin II binding to the human
      endothelin 1 ETA and angiotensin II AT1 receptors, respectively. Selectivity for
      only one of the two receptors was exhibited by asiatic acid and its saponins
      (ETA) and oleanolic acid (AT1). To a lesser extent betulinic acid, beta-amyrin
      and friedelin also showed selectivity for the ETA receptor. To address the
      question whether the effect of saponins on cell membranes might interfere with
      the normal binding of specific radioligands to their receptors, the activity of
      saponins with different haemolytic properties were compared. Highly haemolytic
      saponins such as alpha-hederin and beta-escine showed partial (60%) inhibition of
      radioligand-binding to the ETA receptor and complete inhibition (100%) to the AT1
      receptor. Moreover, the haemolytically inactive kryptoescine, at the same
      concentration, caused complete inhibiton of radioligand-binding to both
      receptors, indicating that inhibition of receptor binding was not related to the
      membrane-interacting properties of saponins.

PMID- 15478203
TI  - Cytoprotective effect on oxidative stress and inhibitory effect on cellular aging
      of Terminalia chebula fruit.
AB  - The ethanol extract from the fruit of Terminalia chebula (Combretaceae) exhibited
      significant inhibitory activity on oxidative stress and the age-dependent
      shortening of the telomeric DNA length. In the peroxidation model using t-BuOOH,
      the T. chebula extract showed a notable cytoprotective effect on the HEK-N/F
      cells with 60.5 +/- 3.8% at a concentration of 50 microg/ml. In addition, the T.
      chebula extract exhibited a significant cytoprotective effect against UVB-induced
      oxidative damage. The life-span of the HEK-N/F cells was elongated by 40% as a
      result of the continuous administration of 3 microg/ml of the T. chebula extract
      compared to that of the control. These observations were attributed to the
      inhibitory effect of the T. chebula extract on the age-dependent shortening of
      the telomere, length as shown by the Southern blots of the terminal restriction
      fragments (TRFs) of DNA extracted from subculture passages.

PMID- 15478204
TI  - Antiviral activities of medicinal herbs traditionally used in southern mainland
      China.
AB  - The aqueous extracts from 21 medicinal herbs traditionally used in southern
      mainland China were screened for antiviral activities against human herpes
      simplex virus type 1 (HSV-1) and human respiratory syncytial virus (RSV) using a
      cytopathic effect (CPE) reduction assay. Three extracts from Agrimonia pilosa,
      Pithecellobium clypearia and Punica granatum, respectively, showed anti-HSV-1
      activity, which was possibly contributed by the polyphenolic compounds in the
      herbal extracts. Six of the extracts, from Blumea laciniata, Elephantopus scaber,
      Laggera pterodonta, Mussaenda pubescens, Schefflera octophylla and Scutellaria
      indica, respectively, exhibited anti-RSV activity with 50% inhibition (IC50)
      concentrations ranging from 12.5 to 32 microg/mL, and selective indices (SI)
      ranging from 11.2 to 40. In addition to polyphenolic compounds, other
      constituents present in these extracts may also contribute to their anti-RSV
      activity.

PMID- 15478205
TI  - Reversal of LPS-induced immobility in mice by green tea polyphenols: possible COX
      2 mechanism.
AB  - An endotoxin (lipopolysaccharide, LPS) is known to activate the hypothalamo
      pituitary adrenocortical axis, as well as norepinephrine and indolamine
      metabolism. Systemically administered LPS produces depression in the forced
      swimming-induced despair behaviour model in mice. The present study was designed
      to investigate the effect of green tea extract (GTE) on LPS-induced despair
      behaviour and to explore the mechanism involved in modulation of LPS-induced
      immobility by GTE. GTE (10-100 mg/kg) pretreatment reversed LPS-induced
      immobility in a dose-dependent manner. Rofecoxib (2 mg/kg) and nimesulide (2
      mg/kg), COX-2 inhibitors, also reversed the LPS-induced immobility, which was
      significantly potentiated by concomitant administration of GTE. On the other
      hand, GTE did not show any potentiating effect on immobility with naproxen (10
      mg/kg), which is a nonselective COX blocker. Interestingly the antioxidant,
      carvedilol (2 mg/kg) did not produce any effect on immobility either in normal or
      in LPS treated mice. The results of the study implicate the role of COX-2
      inhibition by GTE in the reversal of LPS-induced immobility.

PMID- 15478207
TI  - The chemical composition of some Lauraceae essential oils and their antifungal
      activities.
AB  - The antifungal activity of Aniba rosaeodora, Laurus nobilis, Sassafras albidum
      and Cinnamomum zeylanicum essential oils were investigated against 17
      micromycetes. Among the tested fungal species were food poisoning, spoilage
      fungi, plant and animal pathogens. In order to determine fungistatic and
      fungicidal concentrations (MIC and MFC) macrodilution and microdilution tests
      were used. Linalool was the main component in the essential oil of A. rosaeodora,
      while 1.8-cineole was dominant in L. nobilis. In sassafras essential oil safrole
      was the major component and in the oil of C. zeylanicum the main component was
      trans-cinnamaldehyde. The essential oil of cinnamon showed the strongest
      antifungal activity.

PMID- 15478206
TI  - Neuroprotective effects of the antiparkinson drug Mucuna pruriens.
AB  - Mucuna pruriens possesses significantly higher antiparkinson activity compared
      with levodopa in the 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's
      disease. The present study evaluated the neurorestorative effect of Mucuna
      pruriens cotyledon powder on the nigrostriatal tract of 6-OHDA lesioned rats.
      Mucuna pruriens cotyledon powder significantly increased the brain mitochondrial
      complex-I activity but did not affect the total monoamine oxidase activity (in
      vitro). Unlike synthetic levodopa treatment, Mucuna pruriens cotyledon powder
      treatment significantly restored the endogenous levodopa, dopamine,
      norepinephrine and serotonin content in the substantia nigra. Nicotine adenine
      dinucleotide (NADH) and coenzyme Q-10, that are shown to have a therapeutic
      benefit in Parkinson's disease, were present in the Mucuna pruriens cotyledon
      powder. Earlier studies showed that Mucuna pruriens treatment controls the
      symptoms of Parkinson's disease. This additional finding of a neurorestorative
      benefit by Mucuna pruriens cotyledon powder on the degenerating dopaminergic
      neurons in the substantia nigra may be due to increased complex-I activity and
      the presence of NADH and coenzyme Q-10.

PMID- 15478208
TI  - The use of essential oils to treat snoring.
AB  - Snoring is a very common social inconvenience. This double-blind study suggests a
      significant reduction in snoring reported by bed partners in a group of snoring
      volunteers using either an essential oil spray or gargle formulation. Possible
      modes of action of the essential oils are discussed.

PMID- 15478209
TI  - Herbal treatment following post-seizure induction in rat by lithium pilocarpine:
      Scutellaria lateriflora (Skullcap), Gelsemium sempervirens (Gelsemium) and Datura
      stramonium (Jimson Weed) may prevent development of spontaneous seizures.
AB  - About 1 week after the induction of status epilepticus in male rats by a single
      systemic injection of lithium (3 mEq/kg) and pilocarpine (30 g/kg), rats were
      continuously administered one of three herbal treatments through the water supply
      for 30 days. A fourth group received colloidal minerals and diluted food grade
      hydrogen peroxide in tap water, while a fifth group of rats received only tap
      water (control). Herbal treatments were selected for their historical antiseizure
      activities and sedative actions on the nervous system. The numbers of spontaneous
      seizures per day during a 15 min observation interval were recorded for each rat
      during the treatment period and during an additional 30 days when only tap water
      was given. Rats that received a weak solution of the three herbal fluid extracts
      of Scutellaria lateri flora (Skullcap), Gelsemium sempervirens (Gelsemium) and
      Datura stramonium (Jimson Weed) displayed no seizures during treatment while all
      the other groups were not seizure-free. However, when this treatment was removed,
      the rats in this group displayed numbers of spontaneous seizures comparable to
      the controls. Although there is no proof that herbal remedies can control limbic
      or temporal lobe epilepsy, the results of this experiment strongly suggest that
      the appropriate combination of herbal compounds may be helpful as adjunctive
      interventions.

PMID- 15478210
TI  - 1H NMR spectroscopic criteria for the configuration of N-acyl-alpha,beta-dehydro
      alpha-amino acid esters.
AB  - The diagnostic values of the following three spectral criteria for the
      configuration of N-acyl-alpha,beta-dehydro-alpha-amino acid esters were examined:
      (i) the proton at the beta-position at the double bond of a Z-isomer is shielded
      if compared with the respective E-isomer (delta(beta)Z < delta(beta)E); (ii) the
      proton at the nitrogen atom is shielded in a Z-isomer in comparison with the
      corresponding E-isomer (delta(NH)Z < delta(NH)E); and (iii) changing of the
      solvent from CDCl3 to deuterated trifluoroacetic acid (TFA) causes shielding of
      the H(beta) vinylic proton of an E-isomer or deshielding of the respective proton
      of the Z-isomer (delta(CDCl3)E > delta(TFA)E or delta(CDCl3)Z < delta(TFA)Z). The
      investigations were based on a set of 22 (Z)- and (E)-N-acyl-alpha,beta-dehydro
      alpha-amino acid esters of diverse structures, with aliphatic, aromatic and
      heteroaromatic substituents at the vinylic beta-carbon; most of the examined
      compounds were hitherto unknown. The application of the substituent effect
      additivity rule given by Pascual et al. for olefinic protons leads to evidently
      erroneous configuration assignments of N-acyl-alpha,beta-dehydro-alpha-amino acid
      esters. The considered criteria were fulfilled for all the examined cases with
      one exception [the second criterion for the alpha-pivaloylamino-beta-(2
      furyl)acrylates]. The comparison of changes in the chemical shifts of H(beta)
      vinylic protons in CDCl3 and deuterated TFA seems to be the most reliable and
      useful configuration criterion, as it can be used in the case of a single isomer.

PMID- 15478211
TI  - Zinopin--the rationale for its use as a food supplement in Traveller's thrombosis
      and motion sickness.
AB  - Venous thrombo-embolism (VTE) has been associated with periods of prolonged
      immobility during air, sea and road travel. Motion sickness (MS) has also been
      reported during both long and short journeys. Current prophylactic therapies for
      both these indications are generally associated with side effects. Physiological
      profiles of Pycnogenol and Standardized Ginger Root Extract (SGRE) representing
      active constituents of Zinopin have been described and reviewed in relation to
      their activities involved in the patho-physiology of VTE (Traveller's Sickness)
      and MS and their safe use as food supplement, in traveller's thrombosis and
      motion sickness. The pathophysiology of VTE and MS is discussed in light of
      epidemiological data and risk factors associated with these conditions. Rationale
      of development of Zinopin and its mechanism of action are discussed based on
      physiological synergy of Pycnogenol and SGRE. Conclusions are made in light of
      preliminary clinical findings obtained in an open controlled clinical trial.
      Further clinical study on Zinopin on these lines is suggested.

PMID- 15478212
TI  - Bone morphogenetic protein-2 decorated silk fibroin films induce osteogenic
      differentiation of human bone marrow stromal cells.
AB  - Bone morphogenetic protein (BMP)-2 has a critical role in bone formation and
      regeneration. Therefore, the ability to immobilize this molecule in certain
      matrices may be crucial in bone tissue engineering. Using carbodiimide chemistry,
      BMP-2 was directly immobilized on silk fibroin films. Whereas human bone marrow
      stromal cells cultured on unmodified silk fibroin films in the presence of
      osteogenic stimulants exhibited little if any osteogenesis, the same cells
      cultured on BMP-2 decorated films in the presence of osteogenic stimulants
      differentiated into an osteoblastic lineage as assessed by their significantly
      elevated alkaline phosphatase activity, calcium deposition, and higher transcript
      levels of collagen type I, bone sialoprotein, osteopontin, osteocalcin, BMP-2,
      and cbfa1. Using cell culture inserts, it was demonstrated that differentiation
      was induced by the immobilized protein and not by protein released into the
      culture medium. Comparison with a similar amount of medium-supplemented BMP-2,
      where no additional protein was added with medium changes, showed that delivery
      of BMP-2 immobilized on the biomaterial surface was more efficient than soluble
      delivery. The results illustrate that BMP-2 covalently coupled on silk
      biomaterial matrices retains biological function in vitro based on the induction
      of osteogenic markers in seeded bone marrow stromal cells.

PMID- 15478213
TI  - Toxicity detection from EILATox-Oregon Workshop samples by using kinetic
      photobacteria measurement: the Flash method.
AB  - The Flash test, which can be used to measure the toxicity from clear, turbid and
      coloured samples with identical protocol, was used in the EILATox-Oregon
      Workshop. During the workshop, 17 synthetic samples and three environmental
      samples were tested. In the Flash method the photobacteria Vibrio fischeri are
      initially dispensed on top of the sample and the light output of the
      bioluminescence reaction is recorded at a rate of several readings per second.
      The change in the light production was measured at two points: 30 s and 30 min
      after exposure at room temperature. Toxicity calculations were done by using
      either the peak height of the sample or the peak height of the control sample
      (maximum signal at 0-2 s). When the peak height of the sample is used as a
      reference, the colour and turbidity effect of solid particles are taken into
      account throughout the whole measurement period. In the EILATox-Oregon Workshop
      toxicity was seen in samples 1 (chlordimeform), 4 (phosdrin), 5 (HgCl(2)), 6
      (sodium arsenite), 8 (metham sodium), 12 (p-chlorophenol), 14 (sodium selenite)
      and 17 (MNNG). Only samples 1, 4 and 12 showed different ec(50) values between
      different calculations of toxicity. The ec(50) values were calculated and
      compared with the ec(50) values of Microtox derived from the literature. The
      Flash test will not replace the standardized photobacteria test, but is the
      advanced version of it and is needed when the sample matrix is complex and when
      speed and low costs are required.

PMID- 15478214
TI  - Proteomic analysis of the response of Arabidopsis chloroplast proteins to high
      light stress.
AB  - Light is an essential environmental factor in the progression of plant growth and
      development but prolonged exposure to high levels of light stress can cause
      cellular damage and ultimately result in the death of the plant. Plants can
      respond defensively to this stress for a limited period and this involves changes
      to their gene expression profiles. Proteomic approaches were therefore applied to
      the study of the response to high light stress in the Arabidopsis thaliana plant
      species. Wild-type Arabidopsis was grown under normal light (100 micromol
      photons.m(-2).s(-1)) conditions and then subjected to high light (1000 micromol
      photons.m(-2).s(-1)) stress. Chloroplasts were then isolated from these plants
      and both soluble and insoluble proteins were extracted and subjected to two
      dimensional (2-D) gel electrophoresis. The resolved proteins were subsequently
      identified by matrix assisted laser desorption/ionization-time of flight-mass
      spectrometry (MALDI-TOF-MS) and comparative database analysis. 64 protein spots,
      which were identified as candidate factors that responded to high light stress,
      were then selected for analysis and 52 of these were successfully identified
      using MALDI-TOF-MS analysis. 35 of the 52 identified proteins were found to
      decrease their expression levels during high light stress and a further 14 of the
      candidate proteins had upregulated expression levels under these conditions. Most
      of the proteins that were downregulated during high light stress are involved in
      photosynthesis pathways. However, many of the 14 upregulated proteins were
      identified as previously well-known high light stress-related proteins, such as
      heat shock proteins (HSPs), dehydroascorbate reductase (DHAR), and superoxide
      dismutase (SOD). Three novel proteins that were more highly expressed during
      periods of high light stress but had no clear functional relationship to these
      conditions, were also identified in this study.

PMID- 15478215
TI  - Proteomic analysis of pathogen-responsive proteins from rice leaves induced by
      rice blast fungus, Magnaporthe grisea.
AB  - Proteomic approaches using two-dimensional gel electrophoresis (2-DE) were
      adopted to identify proteins from rice leaf that are differentially expressed in
      response to the rice blast fungus, Magnaporthe grisea. Microscopic observation of
      inoculated leaf with M. grisea revealed that callose deposition and
      hypersensitive response was clearly visible in incompatible interactions but
      excessive invading hypha with branches were evident in compatible interactions.
      Proteins were extracted from leaves 24, 48, and 72 hours after rice blast fungus
      inoculation. Eight proteins resolved on the 2-DE gels were induced or increased
      in the inoculated leaf. Matrix-assisted laser desorption/ionization-time of
      flight analysis of these differentially displayed proteins showed them to be two
      receptor-like protein kinases (RLK), two beta-1.3-glucanases (Glu1, Glu2),
      thaumatin-like protein (TLP), peroxidase (POX 22.3), probenazole-inducible
      protein (PBZ1), and rice pathogenesis-related 10 (OsPR-10). Of these proteins,
      RLK, TLP, PBZ, and OsPR-10 proteins were induced more in the incompatible
      interactions than in compatible ones. A phytohormone, jasmonic acid also induced
      all eight proteins in leaves. To confirm whether the expression profile is equal
      to the 2-DE data, seven cDNA clones were used as probes in Northern hybridization
      experiments using total RNA from leaf tissues inoculated with incompatible and
      compatible rice blast fungal races. The genes encoding POX22.3, Glu1, Glu2, TLP,
      OsRLK, PBZ1, and OsPR-10 were activated in inoculated leaves, with TLP, OsRLK,
      PBZ1, and OsPR-10 being expressed earlier and more in incompatible than in
      compatible interactions. These results suggest that early and high induction of
      these genes may provide host plants with leading edges to defend themselves. The
      localization of two rice PR-10 proteins, PBZ1 and OsPR-10, was further examined
      by immunohistochemical analysis. PBZ1 accumulated highly in mesophyll cells under
      the attachment site of the appressorium. In contrast, OsPR-10 expression was
      mainly localized to vascular tissue.

PMID- 15478216
TI  - Proteomic analysis of melanoma-derived exosomes by two-dimensional polyacrylamide
      gel electrophoresis and mass spectrometry.
AB  - Exosomes are 40-100 nm vesicles released by numerous cell types and are thought
      to have a variety of roles depending on their origin. Exosomes derived from
      antigen presenting cells have been shown to be capable of initiating immune
      responses in vivo and eradicating established tumours in murine models. Tumour
      derived exosomes can be utilised as a source of tumour antigen for cross-priming
      to T-cells and are thus of interest for use in anti-tumour immunotherapy. Further
      exploration into the protein composition of exosomes may increase our
      understanding of their potential roles in vivo and this study has examined the
      proteome of exosomes purified from cell supernatants of the melanoma cell lines
      MeWo and SK-MEL-28. The vesicular nature and size (30-100 nm) of the purified
      exosomes was confirmed by electron microscopy and sucrose density gradient
      centrifugation. Western blotting demonstrated the absence of calnexin and
      cytochrome c, verifying the purity of the exosome preparations, as well as
      enrichment of MHC class I and the tumour-associated antigens Mart-1 and Mel-CAM.
      The two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) protein
      profiles of exosomes from the two cell lines were highly comparable and
      strikingly different from the profiles of the total cell lysates. Mass
      spectrometric sequencing identified proteins present in 49 protein spots in the
      exosome lysates. Several of these have been identified previously in exosomes but
      some are novel, including p120 catenin, radixin, and immunoglobulin superfamily
      member 8 (PGRL). Proteins present in whole-cell lysates that were significantly
      reduced or excluded from exosomes were also identified and included several
      mitochondrial and lysosomal proteins, again confirming the proposed endosomal
      origin of exosomes. This study presents a starting point for future more in-depth
      protein studies of tumour-derived exosomes which will aid the understanding of
      their biogenesis and targeting for use in anti-tumour immunotherapy protocols.

PMID- 15478217
TI  - ProteomeGRID: towards a high-throughput proteomics pipeline through opportunistic
      cluster image computing for two-dimensional gel electrophoresis.
AB  - The quest for high-throughput proteomics has revealed a number of critical
      issues. Whilst improved two-dimensional gel electrophoresis (2-DE) sample
      preparation, staining and imaging issues are being actively pursued by industry,
      reliable high-throughput spot matching and quantification remains a significant
      bottleneck in the bioinformatics pipeline, thus restricting the flow of data to
      mass spectrometry through robotic spot excision and protein digestion. To this
      end, it is important to establish a full multi-site Grid infrastructure for the
      processing, archival, standardisation and retrieval of proteomic data and
      metadata. Particular emphasis needs to be placed on large-scale image mining and
      statistical cross-validation for reliable, fully automated differential
      expression analysis, and the development of a statistical 2-DE object model and
      ontology that underpins the emerging HUPO PSI GPS (Human Proteome Organization
      Proteomics Standards Initiative General Proteomics Standards). The first step
      towards this goal is to overcome the computational and communications burden
      entailed by the image analysis of 2-DE gels with Grid enabled cluster computing.
      This paper presents the proTurbo framework as part of the ProteomeGRID, which
      utilises Condor cluster management combined with CORBA communications and JPEG-LS
      lossless image compression for task farming. A novel probabilistic eager
      scheduler has been developed to minimise make-span, where tasks are duplicated in
      response to the likelihood of the Condor machines' owners evicting them. A 60 gel
      experiment was pair-wise image registered (3540 tasks) on a 40 machine Linux
      cluster. Real-world performance and network overhead was gauged, and Poisson
      distributed worker evictions were simulated. Our results show a 4:1 lossless and
      9:1 near lossless image compression ratio and so network overhead did not affect
      other users. With 40 workers a 32x speed-up was seen (80% resource efficiency),
      and the eager scheduler reduced the impact of evictions by 58%.

PMID- 15478218
TI  - High-resolution soft lithography: enabling materials for nanotechnologies.

PMID- 15478220
TI  - Current awareness in prenatal diagnosis.

PMID- 15478219
TI  - Language-association cortex asymmetry in autism and specific language impairment.
AB  - Language deficits are among the core impairments of autism. We previously
      reported asymmetry reversal of frontal language cortex in boys with autism.
      Specific language impairment (SLI) and autism share similar language deficits and
      may share genetic links. This study evaluated asymmetry of frontal language
      cortex in a new, independent sample of right-handed boys, including a new sample
      of boys with autism and a group of boys with SLI. The boys with autism were
      divided into those with language impairment (ALI) and those with normal language
      ability (ALN). Subjects (right-handed, aged 6.2-13.4 years) included 22 boys with
      autism (16 ALI and 6 ALN), 9 boys with a history of or present SLI, and 11 normal
      controls. MRI brain scans were segmented into grey and white matter; then the
      cerebral cortex was parcellated into 48 gyral-based divisions per hemisphere.
      Group differences in volumetric asymmetry were predicted a priori in language
      related regions in inferior lateral frontal (Broca's area) and posterior superior
      temporal cortex. Language impaired boys with autism and SLI both had significant
      reversal of asymmetry in frontal language-related cortex; larger on the right
      side in both groups of language impaired boys and larger on the left in both
      unimpaired language groups, strengthening a phenotypic link between ALI and SLI.
      Thus, we replicated the observation of reversed asymmetry in frontal language
      cortex reported previously in an independent autism sample, and observed similar
      reversal in boys with SLI, further strengthening a phenotypic link between SLI
      and a subgroup of autism. Linguistically unimpaired boys with autism had similar
      asymmetry compared with the control group, suggesting that Broca's area asymmetry
      reversal is related more to language impairment than specifically to autism
      diagnosis.

PMID- 15478222
TI  - Prevention. ACLU raps CDC for guideline proposals for AIDS materials.

PMID- 15478221
TI  - Enhancing treatment responses in depression.

PMID- 15478223
TI  - CDC guidelines. ACLU disputes timeline to finalize guidelines.

PMID- 15478224
TI  - Discrimination. Court: HIV disclosure, dismissal are coincidental.

PMID- 15478225
TI  - Sentencing. Prisoner with HIV and hepatitis C denied habeas relief.

PMID- 15478226
TI  - Drug access. Legislature pledges to lift trade barriers for HIV drugs.

PMID- 15478227
TI  - HIV won't slow population growth in developing nations.

PMID- 15478228
TI  - U.N. issues inaugural series of global HIV/AIDS estimates.

PMID- 15478229
TI  - Disease transmission. Court upholds felony against man who spit on officers.

PMID- 15478230
TI  - Court-ordered testing upheld for man who bit security guard.

PMID- 15478231
TI  - Offender loses challenge of court-ordered HIV testing.

PMID- 15478232
TI  - Criminal exposure. Man who infected wife with HIV must submit to discovery.

PMID- 15478233
TI  - Transfusion. HIV-positive hemophiliac loses claim against blood providers.

PMID- 15478234
TI  - AIDS ride. Negligence claim revived for deceased rider at AIDS fund-raiser.

PMID- 15478235
TI  - AIDS among top ailments responsible for increased spending.

PMID- 15478236
TI  - [Standardization system for health services of the Russian Federation. Guidelines
      for pre-analytical phase of clinical laboratory studies].

PMID- 15478237
TI  - [Standardization system for health services of the Russian Federation. Guidelines
      for assessment of analytical reliability of clinical laboratory tests (precision,
      sensitivity, specificity)].

PMID- 15478238
TI  - [Standardization system for health services of the Russian Federation. Guidelines
      for elaboration of requirements for timely release (in clinically acceptable
      time) of laboratory information].

PMID- 15478239
TI  - [Standardization system for health services of the Russian Federation. Guidelines
      for assessment of informative capacity of clinical laboratory tests].

PMID- 15478240
TI  - [Universal safe injection].

PMID- 15478241
TI  - [Comparison between low-carbohydrate and mediterranean diet].
AB  - Since seventies Robert Atkins promoted a low-carbohydrate, high-protein diet
      without calories counting. This dietetic approach, first described at the end of
      1960 and periodically devised by different authors, is yet object of scientific
      discussion for its efficacy and safety.

PMID- 15478242
TI  - Quadricuspid aortic valve: a chance for repair.
AB  - Quadricuspid aortic valve is an uncommon congenital anomaly that often causes
      aortic regurgitation in adulthood, necessitating valve replacement. A 54-year-old
      woman presented with symptoms and signs of aortic regurgitation, but during
      surgery a quadricuspid aortic valve was identified. The abnormal cusp was
      fibrotic, short, thick, and fenestrated. Excision of the fourth cusp was
      performed and valve repair carried out successfully, with only minimal
      regurgitation.

PMID- 15478244
TI  - Bibliography current world literature. Gastrointestinal tract.

PMID- 15478243
TI  - Bibliography current world literature. Sarcomas.

PMID- 15478245
TI  - Respiratory therapist.

PMID- 15478246
TI  - Child neurology.

PMID- 15478247
TI  - When terrorism threatens health: how far are limitations on personal and economic
      liberties justified?

PMID- 15478248
TI  - Puppy love: bioterrorism, civil rights, and public health.

PMID- 15478249
TI  - Liberalism, communitarianism, and public health: comments on Lawrence O. Gostin's
      lecture.

PMID- 15478250
TI  - Beyond the liberal and communitarian impasse: a framework and vision for public
      health.

PMID- 15478251
TI  - On authority and justification in public health.

PMID- 15478252
TI  - Medicare and Medicaid: are they just health care systems?

PMID- 15478253
TI  - HIV: reasons to apply traditional methods of disease control to the spread of
      HIV.

PMID- 15478254
TI  - No longer the last to know: a proposal for mandatory notification of spouses of
      HIV infected individuals.

PMID- 15478255
TI  - Medical gender bias and managed care.

PMID- 15478256
TI  - Legal issues in end-of-life care in Oklahoma.

PMID- 15478257
TI  - After managed care: gray boxes, tiers and consumerism.

PMID- 15478258
TI  - Genetic information and the importance of context: implications for the social
      meaning of genetic information and individual identity.

PMID- 15478259
TI  - Prescription drugs uses and effect. Beta blockers. Cardiovascular disease.

PMID- 15478260
TI  - Ending parents' unlimited power to choose: legislation is necessary to prohibit
      parents' selection of their children's sex and characteristics.

PMID- 15478261
TI  - Introduction. "Paying the alligator": precommitment in law, bioethics, and
      constitutions.

PMID- 15478263
TI  - Commitment problems in the theory of rational choice.

PMID- 15478264
TI  - Precommitment in bioethics: some theoretical issues.

PMID- 15478265
TI  - Precommitment: a misguided strategy for securing death with dignity.

PMID- 15478266
TI  - Precommitment issues in bioethics.

PMID- 15478267
TI  - Precommitment analysis and societal moral identity.

PMID- 15478268
TI  - [Pro and contra -- adjuvant therapy in locoregional advanced prostatic carcinoma
      after radical prostatectomy].

PMID- 15478269
TI  - Changing ethical standards in scientific publication.

PMID- 15478270
TI  - Abstracts of the 40th Annual Symposium of the Czech Society of Histochemistry and
      Cytochemistry. 16-18 September 2003.

PMID- 15478271
TI  - Mapping a zoonotic disease: Anglo-American efforts to control bovine tuberculosis
      before World War I.
AB  - Before World War I, British and American public health officials correlated
      tuberculosis in dairy cattle with severe infections in milk-drinking children.
      They traced bacteria in municipal milk supplies, mapped the locations of infected
      animals, and sought regulatory power to destroy them. Consumers, milk producers,
      municipal officials, veterinarians, and physicians all influenced the shape of
      antituberculosis regulations. Many condemned pasteurization as too costly and as
      masking tubercular contamination and poor sanitation. They saw milk-borne
      tuberculosis as an environmental as well as a bacteriological problem. Similar to
      other zoonotic diseases such as BSE, bovine tuberculosis blurred the boundaries
      between urban and rural, production and consumption, and human and animal bodies.

PMID- 15478272
TI  - "Clever Microbes": bacteriology and sanitary technology in Manchester and Chicago
      during the progressive age.
AB  - A neglected aspect of the history of germ theories is its use in the purification
      of sewage. In the 1890s, progressive reformers rapidly developed bacteriological
      methods of wastewater treatment. A comparison of the United Kingdom's Manchester
      and the United States' Chicago shows, however, that science and technology were
      mediated by political culture and institutions. In Manchester, a politics of
      deference and strong extralocal government gave the authority of scientific
      expertise a decisive role in policy formation. In Chicago, devolution of power to
      the ward bosses meant a quarter-century of defiance against the national
      authority and its effort to get the city to install a modern sanitation system.

PMID- 15478273
TI  - Harold Knapp and the geography of normal controversy: radioiodine in the
      historical environment.
AB  - In 1962, after high levels of the isotope Iodine-131 were detected in Utah milk
      supplies, Dr. Harold Knapp, a mathematician working for the AEC's Division of
      Biology and Medicine, developed a new model of estimating, first, the relation
      between a single deposition of radioactive fallout on pasturage and the levels of
      Iodine-131 in fresh milk and, second, the total dose to human thyroids, resulting
      from daily intake of the contaminated milk. The implications of Knapp's findings
      were enormous. They suggested that short-living radioiodine, rather than long
      living nuclides such as radiostrontium, posed the greatest hazard from nuclear
      test fallout and that children raised in Nevada and Utah during the 1950s had
      been exposed to internal radiation doses far in excess of recommended guidelines.
      This paper explores the explicit historical revisionism of Knapp's study, his
      refusal, contra normal AEC practices of knowledge production and spatial
      representation, to distance himself from the people and places downwind from the
      Nevada Test Site, and the reactions his work provoked among his AEC colleagues.

PMID- 15478274
TI  - The artificial nature of fluoridated water: between nations, knowledge, and
      material flows.
AB  - An exercise in "historical ontology," this paper charts the contrasting ways
      fluoridated water and its effects crystallized as objects of knowledge and
      concern in three quite different realms over the mid twentieth century. Among
      U.S. health officials and experts, fluoridated water emerged and stabilized as a
      public health goal, preventing tooth decay. Indian doctors and scientists defined
      it as a public health problem, causing "skeletal fluorosis." Fluoridated water
      also acquired an intense presence among laypeople in the United States,
      especially those voting in local referenda on fluoridation. More often than not
      rejecting it, suspecting bias and myopia in profluoridation expertise, they
      cobbled together a lay ontology that proved predictive of the varied and changing
      flows of fluoridated water itself. The paper concludes by suggesting a principle
      of environmental symmetry as an aid to this kind of comparative ontology.

PMID- 15478275
TI  - A role for Ran-GTP and Crm1 in blocking re-replication.

PMID- 15478276
TI  - Bibliography of toxinology.

PMID- 15478277
TI  - Cholesterol-gallstone formation: more than a biliary lipid defect?

PMID- 15478278
TI  - Neutrophils, myeloperoxidase, and bronchiectasis in cystic fibrosis: green is not
      good.

PMID- 15478279
TI  - Recruiting for a clinical study (disparities in health care and research).

PMID- 15478280
TI  - The fruits of ill-health: Pesticides and workers' bodies in post-World War II
      California.
AB  - In the postwar period, modernist frameworks of the human body, which described
      the body as both cosmopolitan and separated from its environment, competed with
      ecological frameworks that constructed the body as inherently porous and tightly
      linked to the surrounding world. The history of pesticide-related illness among
      farmworkers, and the gradual recognition that pesticides posed a new kind of
      public health problem, illustrates how these competing understandings were
      adopted, mobilized, and applied by different groups, as well as how politics
      shaped the emergence of new medical facts. New forms of illness generated new
      knowledge about the modern landscape and made visible material links between
      bodies and their environments.

PMID- 15478282
TI  - Abstracts of the 56th Annual Meeting of the German Society of Hygiene and
      Microbiology. 26-29 September 2004, Munster, Germany.

PMID- 15478281
TI  - Transcatheter Cardiovascular Therapeutics, 16th annual symposium. Washington, DC,
      USA, September 2004. Abstracts.

PMID- 15478283
TI  - [XIX National Congress of the SOFMER (French Society of Physical Medicine and
      Rehabilitation). Paris, France, 30 September-2 October 2004. Abstracts].

PMID- 15478284
TI  - Abstracts of the 3rd International Chicago Symposium on Malignancies of the Chest
      and Head and Neck. Chicago, Illinois, USA, October 7-9, 2004.

PMID- 15478285
TI  - Abstracts for the 6th International Symposium on Hodgkin's Lymphoma. Cologne,
      Germany, 18-21 September 2004.

PMID- 15478286
TI  - Findings of scientific misconduct.

PMID- 15478287
TI  - [Probiotics].

PMID- 15478288
TI  - [The perspective of global eradication of poliomyelitis].

PMID- 15478289
TI  - ACE cardiovascular protection: EUROPA versus HOPE.

PMID- 15478290
TI  - Brain natriuretic peptide as a surrogate marker in heart failure trials.

PMID- 15478291
TI  - [Use and misuse of antibiotics. Time to evaluate it beyond humans].
AB  - Antibiotics, once called the "wonder drugs" might be loosing their magic through
      development and dissemination of bacterial resistance. We are very responsible
      for that by way of inappropriate and excessive use of them. Although we have not
      created the problem we have promoted, accelerated and amplifed it. So we used to
      think. Now we can share the blame: massive use in animal feed, seems to be
      contributing a great deal to the same effect, and they are not even used to treat
      infections, but to promote growth and weight gain. Dubious purpose, since same
      effects can be achieved with better and more hygienic feeding practices. Equal or
      larger amounts of antibiotics are thought to be used for this purpose than for
      human health. Resistance in animal flora and transmission to humans has been
      inevitable. In this issue, F Cabello reports this practice in Chilean
      aquaculture: greater amounts than in other countries and a wider range of
      antimicrobials are used here, some sharing chemical and spectrum properties with
      those for human use, some slowly biodegradable. This situation may have a great
      impact in bacterial resistance locally, along with other untoward consequences of
      exposing unnecessarily salmons, humans and the environment to bioactive products.
      The time to openly discuss the practice, probably quite unknown to the general
      public, and perhaps to some authorities, has come.

PMID- 15478293
TI  - [Maternal obesity and reproductive risk].
AB  - BACKGROUND: The prevalence of obesity in school children and pregnant women, a
      known risk factor of the reproductive cycle, has increased significantly over the
      last few years. AIM: To analyze the association between maternal obesity and the
      outcome of pregnancy and newborn health. To quantify the attributable population
      risk of obesity in relation to negative events of pregnancy. MATERIAL AND
      METHODS: A prospective study in 883 pregnant women of 6 public health centers in
      Santiago. Weight, height, arm circumference, skinfold thicknesses, body mass
      index (BMI) and fat mass were determined in each trimester. Maternal socio
      demographic history, smoking habits, incidence of diseases during pregnancy,
      labor and newborn characteristics were analyzed. Logistic regressions of multiple
      factors were used to determine nutritional and non-nutritional variables
      associated to negative events, to determine the population attributable risk of
      each variable that the model retained. RESULTS: Controlling the effect of other
      variables, a BMI > or = 30 or initial body fat mass > or = 35% determined a
      greater risk for assisted labor with an odds ratio (OR) of 1.9 (95% confidence
      interval (CI) 1.3-2.9), gestational diabetes with an OR of 6.4 (95% CI 2.1-19.6),
      hypertension with an OR of 7.8 (95% CI 3.0-20.4), late fetal mortality with an OR
      of 3.4 (95% CI 1.2-10.0), p < 0.001. The risk was mostly associated with the
      initial maternal nutritional status and in a lesser degree, with the weight
      gained during pregnancy. CONCLUSIONS: Maternal obesity is an important risk
      factor during pregnancy. The prenatal control obesity could reduce approximately
      10% of the cesarean sections and late fetal deaths and half of the hypertension
      and gestational diabetes cases.

PMID- 15478292
TI  - [Contemporary practice of the coronary angioplasty in Chile. Final report of the
      Chilean National Coronary Angioplasty Registry (RENAC) 2001-2002].
AB  - BACKGROUND: Coronary angioplasty was introduced in Chile in 1982, but only after
      the introduction of stents it became commonplace. However the results of this
      procedure at the national level remain largely unknown. AIM: To assess the
      results and characteristics of coronary angioplasty and develop a national
      registry in Chile (RENAC). PATIENTS AND METHODS: All centers performing
      angioplasty were invited to contribute prospectively with the clinical,
      angiographic, procedural characteristics and results of all consecutive coronary
      angioplasty procedures attempted between June 2001 and October 2002. RESULTS: In
      10 centers, 1768 lesions were treated in 1484 procedures (22.98% in women). Mean
      age was 60.8 +/- 11.3 years old. Diabetes was found in 21.8%, hypertension in
      60.2%, dyslipidemia in 52.0%, active smoking in 40.0%, renal failure in 6.2%.
      Myocardial infarction was recent in 28.4% and acute in 19.7%. Forty eight percent
      of patients had unstable angina and 15.5% had stable angina. Fifty three percent
      of patients had single vessel disease and 71%, normal left ventricular eyection
      fraction. One vessel was treated in 90.6% of patients and 81.7% of lesions were
      treated with stents, 17.9% only with baloon and in 0.4% with atherectomy.
      Angiographic success was obtained in 95.2%. Clinical success was obtained in
      92.2%, and 95.1% In patients without acute myocardial infarction. Overall
      inhospital death was 2.2%. In patients without myocardial infarction, the figure
      was 1.1%. CONCLUSIONS: Coronary angioplasty in Chile is performed mostly for the
      treatment of acute coronary syndromes. Stents are the most frequently used
      devices. The high success, low mortality and complications observed are
      comparable to North American registries.

PMID- 15478294
TI  - [Incidence of gestational diabetes and relationship to obesity in Chilean
      pregnant women].
AB  - BACKGROUND: Gestational diabetes (GDM) is associated to a worse outcome of
      pregnancy. This justifies efforts for finding possible causes of GDM that would
      allow implementing preventive interventions. AIM: To study incidence of GDM and
      its relation with obesity and other traditional risk factors. MATERIAL AND
      METHODS: A retrospective study was performed in 234 women who had delivered a
      singleton during the last 12 months, attended in an outpatient clinic in
      Santiago, Chile. Familiar and personal history, body mass index (BMI),
      obstetrical-related pathology and data about the labor and the newborn were
      analyzed. RESULTS: GDM was diagnosed in 11.2% of the women. BMI before pregnancy
      was 26.6 +/- 4.4 kg/m2 (mean +/- SD) and it was 25 or over in 37.8% of women.
      Women who developed GDM had significantly higher BMI in the pre-pregnancy stage
      and in the second and third trimester of pregnancy (p < 0.001). The average age
      was greater in the GDM group (31 +/- 0.2 yr versus 26 +/- 0.41 yr). Incidence of
      GDM was 14.4% among women 25 years old or older and increased to 21.4% when they
      had, in addition, a BMI of 25 or over. Age, BMI, and family history of diabetes
      were all independently correlated with the development of GDM. Elective caesarean
      sections were more common in GDM than in non-GDM women (p < or = 0.01) and
      complications were present in 3/23 of newborns of women with GDM and 2/199 among
      women without GDM (p < 0.01) CONCLUSIONS: GDM and obesity are highly prevalent in
      Chilean pregnant women. BMI, first degree relative with DM and age are
      independent risk factors for the development of GDM.

PMID- 15478295
TI  - [Gastrointestinal motility disturbances in Chagas disease].
AB  - Serum antibodies against Trypanosoma Cruzi have been observed in 19% of the
      Chilean population. Marked differences in organ involvement have been reported in
      patients with Chagas disease. Chagas disease is rarely an aetiological factor for
      achalasia in Chile, which is different from reports in other countries of South
      America. In contrast, a high incidence of megacolon among these patients have
      been reported. AIM: To study the incidence of gastric and small intestinal motor
      disorders among these patients and their relationship to esophageal and colon
      motility disorders. PATIENTS AND METHODS: We studied 18 patients, 12 women (mean
      age 45 years); with positive antibodies against T. Cruzi. Seven had radiological
      evidence of megacolon and no one had radiological or manometric evidence for
      achalasia. Non specific motor esophageal abnormalities were found in 11 patients.
      Nine had an abnormal electrocardiogram, suggesting a myocardial disease. A
      questionnaire for gastrointestinal symptoms, an electrogastrography and a small
      intestinal motility study, were performed in each patient. RESULTS: All patients
      had evidences of abnormalities in at least one segment of the digestive tract.
      Twelve patients had an abnormal electrogastrographic study, with bradygastria as
      the most common finding. Nine had an abnormal small intestinal manometry with a
      myophatic pattern evidenced by a decreased amplitude of contractions (18.5 +/- 3
      mmHg). Also an increased number of clustered contractions was observed.
      CONCLUSIONS: Gastric dysrhythmias and small intestinal motor abnormalities are
      frequently associated to non specific esophageal motor disorders and megacolon in
      patients with Chagas disease.

PMID- 15478296
TI  - [Bone marrow edema syndrome of the hip].
AB  - BACKGROUND: Bone marrow edema syndrome (BMES) is a rare clinical condition. Its
      etiology is unknown and it can be seen in different locations. In the case of the
      hip, avascular necrosis is the main differential diagnosis. AIM: To present our
      experience of BMES of the hip and a review of the literature. PATIENTS AND
      METHODS: Retrospective analysis of clinical records of patients with hip pain
      that met clinical, radiological, and magnetic resonance imaging criteria for
      BMES. Clinical outcome and clinical and radiological follow up are presented.
      RESULTS: Two men and two women (one of them pregnant) aged 42, 48, 36 and 26
      years old, fulfilled criteria. Treatment included limited weight bearing, non
      steroidal antiinflammatory drugs, intranasal calcitonin and physical therapy.
      Complete remission of symptoms was observed within five to seven months. At an
      average follow up of 36 months, all patients presented complete function of the
      hip, returning to their previous activity levels, with no new episodes of BMES.
      CONCLUSIONS: It is important to be aware of this condition as part of the
      differential diagnosis of hip pain to avoid aggressive and unnecessary diagnostic
      and therapeutic procedures.

PMID- 15478297
TI  - [K-ras gene mutation in gallbladder carcinoma].
AB  - BACKGROUND: Different K-ras mutation frequencies in gallbladder cancer have been
      reported. AIM: To study the frequency of K-ras gene mutations in advanced
      gallbladder carcinoma not associated to anomalous junction of pancreatic-biliary
      duct (AJPBD). MATERIAL AND METHODS: 33 formalin fixed paraffin embedded samples
      of gallbladder carcinoma (30 women, age range 32-86 years) were selected.
      Pancreatic cancer tissue with K-ras mutations was used as control. DNA was
      extracted from the histological section by mean of microdissection and K-ras
      mutations in codon 12 were detected by polymerase chain reaction and restriction
      fragment length polymorphism (RFLP), using previously reported technique.
      RESULTS: Most cases were poorly differentiated adenocarcinomas. K-ras mutation
      was detected in 10 cases (30%) samples. No differences in K-ras mutation
      frequency between subserous and serous tumors were detected and no relation
      between histological features and the mutation was observed. CONCLUSIONS: K-ras
      mutation in codon 12 is present in 30% in our advanced gallbladder carcinomas.
      The study of K-ras mutation in preneoplastic lesions and early carcinonmas will
      be important to determine the role of this gene in the gallbladder carcinogenesis
      in Chile.

PMID- 15478298
TI  - [Gene-gene and gene-environment interactions as modifier factors of prostatic
      cancer risk: "a case-only" design study].
AB  - BACKGROUND: The role of susceptibility low penetrance genes and environmental
      factors in the etiology of prostate cancer (PCa) is unclear, but may involve in
      some cases multiple alleles at multiple loci. AIM: To evaluate the association of
      gene-gene and gene-environment interactions with PCa. PATIENTS AND METHODS: One
      hundred three subjects with biopsy proven PCa were studied, using a case-only
      design. All were interrogated about smoking habits. Polymorphisms for Glutathione
      S-transferase (GS7) and Cytochrome P4501A1 (CYP1A1), were measured in DNA
      extracted from peripheral lymphocytes, using a restriction fragment length
      polymorphism analysis. RESULTS: Our findings suggest that gene-gene interactions
      between GSTT1 and CYP1A1 high risk genotypes were positive modifiers and had a
      high predictive value for the presence of PCa, compared with non-susceptibility
      genotypes. The interaction between susceptibility genotypes and smoking did not
      modify the risk for PCa. CONCLUSIONS: Gene-gene interactions may play a role
      modulating the susceptibility to PCa in a proportion of affected individuals.

PMID- 15478299
TI  - [Concordance of Gleason histological scoring for prostatic cancer in needle
      biopsies and the surgical piece obtained during radical prostatectomy].
AB  - BACKGROUND: The Gleason histological score is an independent prognostic factor in
      prostate cancer that helps in therapeutic decisions. AIM: To analyze the
      concordance between the Gleason score of needle prostatic biopsy and the score
      from the study of the surgical piece obtained during radical prostatectomy.
      MATERIAL AND METHODS: Retrospective analysis of 212 cases of prostate cancer,
      diagnosed between February 1993 and March 2003. All had the Gleason histological
      scores from needle prostatic biopsies and in the surgical piece obtained during
      radical prostatectomy. All pathological studies were done by the same observer.
      RESULTS: There was an exact concordance of Gleason scores between needle biopsy
      and the surgical piece in 49% of cases and a concordance of +/- 1 unit in 89%.
      The concordance improved in the second half of the study period. No cases with a
      Gleason score of less than 5 were detected since 1999 in the surgical piece.
      CONCLUSIONS: The concordance of Gleason score of needle prostatic biopsies and
      surgical pieces is good. This concordance increases with the experience of the
      pathologist.

PMID- 15478300
TI  - [Risk markers for insulin-dependent diabetes mellitus and duration of exposure to
      gluten in celiac patients].
AB  - BACKGROUND: Celiac patients are at high risk of developing insulin-dependent
      diabetes mellitus, a condition that has a long pre-diabetic period. During this
      lapse, anti-islet cell antibodies serve as markers for future disease. This may
      be related with the duration of the exposure to gluten. AIM: To test the
      hypothesis that long term adherence to a gluten free diet decreases the frequency
      of risk markers for insulin dependent diabetes mellitus during adolescence and
      early adulthood. PATIENTS AND METHODS: 158 celiac patients were classified as:
      G1, (n=30 patients) studied at the time of diagnosis; G2 (n=97 patients) exposed
      to gluten as a result of non compliance with the gluten free diet and, G3 (n=31
      patients) who had maintained a long term, strict gluten free diet. Isotype IgG
      anti-islet cell antibodies were detected by indirect immunofluorescence using
      monkey pancreas, results were reported in Juvenile Diabetes Foundation (JDF)
      units. RESULTS: Celiac patients exposed to a gluten containing diet had a
      significantly higher prevalence of anti-islet cell antibodies than those who had
      been exposed only briefly (p < 0.017). In addition, a significantly higher
      prevalence of anti-islet cell antibodies was observed in those patients whose
      exposure to gluten was longer than 5 years than in those whose exposure was
      shorter (p < 0.02). CONCLUSIONS: Celiac patients long exposed to gluten have a
      significantly higher prevalence of anti-islet cell antibodies than those exposed
      for a short period. This fact supports the hypothesis that the development of
      these antibodies is associated with the length of the exposure to gluten.

PMID- 15478301
TI  - [Atypical presentation of a colorectal carcinoma].
AB  - We report a 67 years old male with a history of pulmonary tuberculosis at the age
      of 15, that consults for malaise, weight loss and productive cough. Chest X ray
      examination showed a left pleural effusion. A pleural tap obtained a sterile
      exudate. A thorax CAT scan showed a proliferating mass in the splenic angle of
      the colon, with left lung and diaphragmatic invasion. Endoscopic biopsies
      confirmed the diagnosis of adenocarcinoma. The patient underwent a subtotal
      colectomy with partial excision of diaphragm and left lung. The pathological
      report showed a mucosecretory adenocarcinoma, infiltrating the pericolonic
      adipose tissue without adjacent organ infiltration and a chronic inflammatory
      process involving colonic serosa, diaphragm pleura, and lung. Adjuvant
      chemotherapy was indicated and the patient is asymptomatic and without evidences
      of tumor recurrence after a 24 months follow up.

PMID- 15478302
TI  - [Bone marrow aplasia during hemodialysis successfully treated with cyclosporine.
      Report of one case].
AB  - A 28 years old male on chronic hemodialysis for 40 months due to a IgA crescentic
      glomerulonephritis developed pancytopenia (hematocrit 16%, white blood cell count
      3,800 mm3 and platelets 11,000 mm3. The bone marrow aspirate showed
      erythropoietic hyperplasia. Hemolytic anemia, folate or vitamin B12 deficiency
      and paroxysmal nocturnal hemoglobinuria were ruled out. Steroids were given with
      a transient elevation of red cells and platelets, which lasted only for some
      weeks. Afterwards, intravenous immunoglobulin was given without benefit. Two
      months after, a bone marrow biopsy and a bone marrow magnetic resonance imaging
      showed severe aplasia. Cyclosporine was started with a rapid increase in blood
      cells count. Eight months later, he received a renal transplant from a cadaveric
      donor. Immunosupression was achieved with cyclosporine, prednisone and
      mycofenolate mofetil. The patient required hemodialysis for the first three weeks
      and a mild acute cellular rejection was treated with methylprednisolone. At
      discharge, 6 weeks later, serum creatinine was 2.4 mg/dl and creatinine clearance
      37.6 ml/min. During the first months after transplant, platelet count and
      hemoglobin decreased and a bone marrow biopsy showed only mild hypoplasia. Four
      months after renal transplant the hematocrit was 43%, white blood cell count
      6,600 mm3 and platelets, 150,000 mm3 and did not change during the first year of
      follow up.

PMID- 15478303
TI  - [Persistent neonatal hyperinsulinism. Analysis of the differential diagnosis.
      Report of two cases].
AB  - Persistent neonatal hyperinsulinism is the most common cause of refractory
      hypoglycemia during the first year of life. Inadequate insulin secretion is
      associated to mutations of four different genes, that can be diagnosed to orient
      patient management. We report two patients: a female newborn that presented a
      hypoglycemia of 16 mg/dl two hours after birth, was subjected to a subtotal
      pancreatectomy that did not correct hypoglycemia, requiring a total
      pancreatectomy. Pathological study of the pancreas showed a focal adenomatous
      hyperplasia. At the present time, she is three years of age and maintains
      euglycemia with fractionated feeding. A male newborn that had seizures at 28
      hours of life and a hypoglycemia of 15 mg/dl was detected. He was also subjected
      to a subtotal pancreatectomy, that did not correct hypoglycemia and bad to be
      extended to a total pancreatectomy. At the present time, he is 3 years and 11
      months of age and has a normal psychomotor development.

PMID- 15478304
TI  - [Antibiotics and aquaculture in Chile: implications for human and animal health].
AB  - Industrial antibiotic usage in agribusinesses and aquaculture is the force that
      drives the evolution of antibiotic resistant bacteria that produce human and
      animal disease in many countries. Several studies have demonstrated that most of
      the industrial use of antibiotics is unnecessary, and that modernization and
      hygienic changes can reduce this use of antibiotics without negative economic
      impact. In Chile, industrial aquaculture of salmon has expanded rapidly in the
      last 20 years becoming a major export business. The exponential growth of this
      industry has been accompanied by an unrestricted heavy usage of antibiotics in
      the aquatic environments of lakes, rivers and the ocean, and its impact is being
      felt in the emergence of antibiotic-resistant bacteria around aquaculture sites
      and a decrease in the plancktonic diversity in the same areas. The passage of
      antibiotic resistance genes from aquatic bacteria to human and animal pathogens
      has been demonstrated, indicating that industrial use of antibiotics in
      aquaculture affects negatively the antibiotic therapy of human and animal
      bacterial infections. The Chilean situation triggers important concerns because
      it includes the use of fluoroquinolones in aquaculture, that are not
      biodegradable and are able to remain in the environment for years as well as
      being still effective in treating human infections. The use of large volumes of a
      wide spectrum of antibiotics in an aquatic environment heavily contaminated with
      human and animal pathogens also amplifies the opportunities for gene transfer
      among bacteria, facilitating the emergence of antibiotic resistance and more
      pathogenic bacterial recombinants. The detection of residual antibiotics in
      salmons marketed for human consumption that can modify the normal flora of the
      population also suggests the need for controls on this antibiotic usage and on
      the presence of residual antibiotics in aquaculture food products. This important
      problem of public health demands an active dialogue between government officials
      responsible for protecting public health, aquaculture industry representatives,
      politicians, consumers and professionals dealing with these matters.

PMID- 15478305
TI  - [Why is it essential to randomize a clinical trial on therapy?].

PMID- 15478306
TI  - [Blastocystis. The most frequent intestinal parasitosis in Chile].

PMID- 15478307
TI  - Haplotype analysis and identification of genes for a complex trait: examples from
      schizophrenia.
AB  - For more than a decade there has been intensive research into the genetic
      etiology of schizophrenia, yet it is only recently that the first findings of
      promising genes associating with the disorder have been reported. Linkage
      analyses in families collected from different populations have provided
      relatively well defined genomic loci. These have been typically followed by fine
      mapping studies using single nucleotide polymorphisms (SNPs). A number of
      analysis programs have been produced to test SNPs and their haplotypes for
      association. Typically association has been established to specific haplotypes
      representing an allelic variant of the corresponding gene. The inherent problem
      of multiple testing in the analysis of haplotypes needs to be addressed fully, to
      determine if any of these recent findings can be considered as confirmed
      susceptibility genes for schizophrenia. However, informative haplotypes have
      provided a way to define allelic variants of genes associated with schizophrenia
      in numerous study samples, and are a useful tool in characterizing the extent of
      allelic diversity of putative schizophrenia susceptibility genes within different
      populations.

PMID- 15478308
TI  - Epidemiology and treatment of the metabolic syndrome.
AB  - Recent definitions of the metabolic syndrome from the World Health Organization
      (WHO) and National Cholesterol Education Program (NCEP) have given us a clearer
      picture of the prevalence of the metabolic syndrome and the risks it poses for
      cardiovascular disease and type 2 diabetes. Solid epidemiological and trial
      evidence support lifestyle changes as the main modifiable risk factors, including
      abdominal obesity, sedentary lifestyle and a diet rich in saturated fat and low
      in fiber content, in the treatment of individual components of the metabolic
      syndrome. Physical activity may prevent the metabolic syndrome as defined by the
      WHO and NCEP, but the evidence for lifestyle changes using these definitions is
      still sparse. No trials on the treatment of the metabolic syndrome to prevent
      diabetes have been published. However, both the Finnish Diabetes Prevention Study
      and the Diabetes Prevention Program found that moderate lifestyle interventions
      in persons with impaired glucose tolerance, a condition related to the metabolic
      syndrome. decreased the incidence of type 2 diabetes by 58%. Some drugs may also
      prevent diabetes. Further research on lifestyle modifications in the prevention
      and treatment of the metabolic syndrome, and on how best to promote lifestyle
      changes, is needed. In the meantime, efforts to curb obesity and overweight,
      increase physical activity and improve compliance with current dietary
      recommendations should continue.

PMID- 15478310
TI  - Target intervention against multiple-risk markers to reduce cardiovascular
      disease in patients with type 2 diabetes.
AB  - The risk of cardiovascular disease is markedly increased in patients with type 2
      diabetes with a prevalence twice as high compared to the background population.
      With the recognition of multiple concomitant risk factors for both microvascular
      as well as cardiovascular disease in type 2 diabetic patients, treatment
      strategies have changed during recent years. This review focuses on the many
      recent drug trials that have set the course for an effective multifactorial
      treatment of the disease. Thus, the Steno-2 Study has shown that an intensified
      multifactorial intervention targeting several risk factors for cardiovascular
      disease is capable of reducing the risk for a combined endpoint of cardiovascular
      mortality, non-fatal myocardial infarction, non-fatal stroke, coronary
      interventions, revascularisation to legs, and amputations by 50%.

PMID- 15478309
TI  - CD163: a regulated hemoglobin scavenger receptor with a role in the anti
      inflammatory response.
AB  - CD163 is a hemoglobin scavenger receptor exclusively expressed in the monocyte
      macrophage system. A particularly high expression is seen in macrophages of the
      'alternative activation' phenotype playing a major role in dampening the
      inflammatory response and in scavenging components of damaged cells. CD163
      mediated endocytosis of haptoglobin-hemoglobin complexes formed upon red blood
      cell hemolysis leads to lysosomal degradation of the ligand protein and
      metabolism of heme by cytosolic heme oxygenase. In accordance with a stimulated
      expression of haptoglobin, CD163 and heme oxygenase-1 during the acute phase
      response, there is evidence that this metabolic pathway regulates inflammation by
      at least two ways. First, CD163 is reported to directly induce intracellular
      signaling leading to secretion of anti-inflammatory cytokines. Second and perhaps
      even more important, the CD163-mediated delivery of hemoglobin to the macrophage
      may fuel an anti-inflammatory response because heme metabolites have potent anti
      inflammatory effects. In addition to being present on the macrophage surface,
      continuous shedding of the extracellular domain of CD163 leads to substantial
      amounts of soluble receptor in plasma. An increased shedding is due to
      inflammatory stimuli, and a role for soluble CD163 in immune suppression has been
      proposed. Furthermore, recent data indicate that soluble CD163 may be a valuable
      diagnostic parameter for monitoring macrophage activation in inflammatory
      conditions.

PMID- 15478311
TI  - DISC1 and DISC2: discovering and dissecting molecular mechanisms underlying
      psychiatric illness.
AB  - A balanced (1;11)(q42;q14) translocation co-segregates with schizophrenia and
      major affective disorders in a large Scottish family. The translocation
      breakpoint on chromosome 1 is located within the Disrupted in Schizophrenia 1 and
      2 genes (DISC1 and DISC2). Consequently loss of normal function of these genes is
      likely to underlie the susceptibility to developing psychiatric disorders that is
      conferred by inheritance of the translocation. Additionally, a number of
      independent genetic studies highlight the region of chromosome 1q containing
      DISC1 and DISC2 as a likely susceptibility locus for both schizophrenia and
      affective disorders. These genes are thus implicated in the aetiology of major
      psychiatric disorders in several populations. Although the function of DISC1 was
      initially unknown, several recent reports have made significant progress towards
      understanding its role in the central nervous system. Intriguingly, all data
      obtained to date point towards an involvement in processes critical to
      neurodevelopment and function. DISC2 has not been studied in detail, but is
      likely to modulate DISC1 expression. Overall, it is clear from the combination of
      genetic and functional data that DISC1 and/or DISC2 are emerging as important
      factors in the molecular genetics of psychiatric illness.

PMID- 15478312
TI  - Molecular basis and diagnostics of hereditary colorectal cancers.
AB  - Hereditary colorectal cancer syndromes are classified according to the presence
      of unusually large number of adenomatous or hamartomatous polyps, or their
      absence. The latter category includes hereditary non-polyposis colorectal cancer
      (Lynch syndrome) and its variants Muir-Torre and Turcot's syndromes. Adenomatous
      polyposis syndromes include familial adenomatous polyposis (FAP) and its
      variants, and the recently identified MYH- (mutY homolog)-associated polyposis.
      Hamartomatous polyposis syndromes include juvenile polyposis, Peutz-Jeghers
      syndrome, and Cowden syndrome, which is now included within the broader category
      'PTEN (phosphatase and tensin homolog) hamartoma tumour syndrome'. Other
      syndromes such as the 'hereditary breast and colon cancer' and 'familial
      colorectal cancer' are not yet fully characterized. This review addresses the
      molecular basis of these syndromes with particular reference to the recent
      advances in this rapidly progressive field and the applications of such knowledge
      in diagnosis and management.

PMID- 15478313
TI  - The infant growth of boys who later develop coronary heart disease.
AB  - BACKGROUND: The association between low birth-weight and coronary heart disease
      has been repeatedly shown. Only two previous studies have examined the effects of
      weight gain during infancy and later coronary heart disease. AIM: The aim of this
      study was to assess the association between infant growth and coronary heart
      disease in adult life. METHODS: 2345 men born at the Helsinki City Maternity
      Hospital during 1934-44 with information on birth size and growth during infancy
      and childhood were included in the study cohort. RESULTS: There was a 3-fold fall
      in hazard ratios for coronary heart disease between men who weighed < or = 8 kg
      at 1 year and those who weighed > 12 kg (P < 0.00001). The fall was steeper among
      men whose placental weight at birth was below average. Men born into families
      with low socio-economic status had lower weight gain during infancy and higher
      rates of coronary heart disease. The increased risk of coronary heart disease in
      men who grew slowly during infancy was greatest in those who had low placental
      weight at birth. CONCLUSIONS: Poor infant growth and small body size at one year
      predict coronary heart disease more strongly than low birth-weight.

PMID- 15478314
TI  - Postmenopausal estrogen therapy and serum estradiol fatty acid esters in women
      with and without previous intrahepatic cholestasis of pregnancy.
AB  - BACKGROUND: Fatty acid esters of 17beta-estradiol (E2) are estrogen metabolites
      associated with lipoproteins in blood. AIM: To study the effects of estrogen
      therapy on concentrations of serum E2 fatty acid esters in postmenopausal women
      with a history of an estrogen-related liver disorder, intrahepatic cholestasis of
      pregnancy (ICP), and in healthy women in a double-blind, crossover fashion.
      METHOD: ICP (n = 10) and control women (n = 10) received increasing doses of E2
      valerate orally 2-4 mg/day, or transdermal E2 50-100 microg/day for 6 weeks.
      After a 4-week wash-out period, the subjects crossed over to the alternate E2
      treatment. Concentrations of serum E2 fatty acid esters were quantified after
      saponification by fluoroimmunoassay. RESULTS: Oral E2 administration increased
      median serum E2 fatty acid ester concentrations from 57 to 73 pmol/L in the ICP
      and from 56 to 74 pmol/L in the control group, in association with elevations in
      serum E2, estrone and sex hormone-binding globulin levels. Transdermal E2
      treatment did not increase serum E2 ester levels. CONCLUSIONS: The increase in
      serum E2 fatty acid esters during oral E2 administration may be attributed, at
      least partly, to the higher estrogen dose during oral compared with transdermal
      therapy. A history of ICP did not affect esterification of E2 during estrogen
      therapy.

PMID- 15478315
TI  - [The 7th National Gerontology Congress].

PMID- 15478316
TI  - [The use of reminiscing].

PMID- 15478317
TI  - [Epidemiology from a life's perspective].

PMID- 15478318
TI  - Transitions from work to retirement: changing experiences of older workers in the
      twenty-first century.

PMID- 15478319
TI  - [The Location Learning Test as a measure of spatial memory: applicability of a
      modified administration procedure and normative data].
AB  - The Location Learning Test is a neuropsychological test that can be used to
      assess memory for object locations. The test has originally been developed for
      the assessment of visuo-spatial memory impairment in patients with dementia.
      However, ceiling effects may be present in other patient groups. This study has
      examined the applicability of a modified administration procedure with a shorter
      presentation duration and longer delay. The test was administered in a group of
      stroke patients (n = 105), a group of patients with diabetes (n = 93), as well as
      a group of healthy volunteers (n = 97). The results indicate that the Location
      Learning Test can be used to discriminate the diabetes and stroke patients from
      the control group. Furthermore, differences between patients with a left and a
      right-hemisphere stroke were found. The test has a high correlation with another
      memory test. The performance of the group healthy volunteers was used to
      calculate normative data for use in clinical practice.

PMID- 15478320
TI  - [Is pulse oximetry a reliable tool for detection of aspiration?].
AB  - This study was designed to determine whether significant differences in
      saturation levels existed among patients with aspiration and patients without and
      wether pulse oximetry can reliably detect aspiration in patients with dysphagia.
      We also examined the effects of gender and disease (neurologic versus non
      neurologic) on saturation levels. We studied 38 patients. They all underwent a
      videofluoroscopic study of swallowing (VFSS). Twenty patients aspirated on
      videofluoroscopic study of swallowing: ten patients were solid aspirators, ten
      patients were liquid aspirators. In each group (liquid aspirators, solid
      aspirators or non aspirators) we found no significant difference in saturation
      levels. We found however a significant difference in saturation levels between
      each group before, during and after videofluoroscopic study of swallowing. Both
      gender and disease had an effect on saturation levels. We conclude that pulse
      oximetry can not serve as a screening tool for detection of aspiration as
      saturation levels are dependent on many factors. Therefore one can not reliably
      predict aspiration with a single saturation screening.

PMID- 15478321
TI  - Predictors of failure in direct stenting in the real world.
AB  - INTRODUCTION: Stent implantation without predilation simplifies a large
      proportion of coronary intervention procedures, with a significant reduction in
      costs and procedure time. OBJECTIVES: To determine the variables associated with
      a higher probability of failure in direct stent implantation in daily practice in
      a wide range of clinical contexts and types of lesions. POPULATION AND METHODS:
      Over a period of 28 months, direct implantation of 931 stents was attempted in
      our Center (811 patients, 83% male, mean age 62 +/- 12 years; 1.1 stent per
      patient). In 59 patients (7.3%), balloon predilation was necessary, and the
      factors associated with direct implant failure were determined. RESULTS: The
      vessels treated were: anterior descending (373 lesions: 40.1%), right coronary
      artery (306 lesions: 32.9%, circumflex (210 lesions: 22.6%), saphenous vein (35
      lesions: 3.8%), left main (5 lesions: 0.4%) and internal mammary artery (2
      lesions: 0.2%). 54% of the lesions were of type B2/C (ACC/AHA classification).
      The characteristics significantly associated with, or with statistical tendency
      towards, a lower success rate in direct stent implantation were: Lesion in the
      circumflex (11% vs. 5.5%, p = 0.012); reference vessel diameter less than 3.0 mm
      (9.8% vs. 6.2%, p = 0.097); age over 65 years (8.5% vs. 4.5%, p = 0.017); left
      main disease, irrespective of the vessel treated (23.5%% vs. 6.5%, p = 0.023);
      B2/C lesion (7.8%, vs. 4.8%, p = 0.086); calcification (9.9% vs. 4.9%, p =
      0.012); vessel angulation greater than 45 degrees (9.9% vs. 4.9%, p = 0.009); and
      Express stent implant (19.6% vs. 6.0%, p < 0.001). On multivariate analysis,
      independent predictors of failure in direct stent implantation were: left main
      lesion (RR 6.6; 95% CI 1.73-24.93; p = 0.013), presence of calcium (RR 1.9; 95%
      CI 1.02-3.37; p = 0.049), vessel curvature (RR 2.0; 95% CI 1.13-3.64; p = 0.018),
      reference vessel diameter less than 3 mm (RR 2.2; 95% CI 1.15-4.32; p = 0.023),
      lesion type B2/C (RR 1.9; 95% CI 1.0-3.52; p = 0.044) and Express stent (RR 2.7;
      95% CI 1.07-6.79; p = 0.05). CONCLUSION: In a large and heterogeneous series of
      patients, direct stenting was not possible in 7.3% of cases, which required
      balloon predilation. Certain clinical and angiographic features can predict when
      this is more like to occur.

PMID- 15478322
TI  - Electrocardiographic identification of the infarct-related artery in acute
      inferior myocardial infarction.
AB  - INTRODUCTION: Mortality and morbidity from acute inferior myocardial infarction
      (MI) are determined, among other factors, by the infarct-related artery (IRA).
      Several electrocardiographic (ECG) criteria have been proposed to differentiate
      between the right coronary artery (RCA) and the left circumflex coronary artery
      (LCx) as the IRA in inferior MI. Recently, a new criterion has been proposed (ST
      segment depression in lead aVR). It was our objective to evaluate the old and the
      new ECG criteria in identifying the IRA in patients with inferior MI. METHODS:
      Patients with inferior MI treated by primary angioplasty were included, following
      evaluation of the admission ECG. Patients with a previous history of Q-wave
      myocardial infarction and complete bundle branch block were excluded. The artery
      with the most severe lesion was considered the IRA. The following ECG criteria
      were assessed: ST depression in lead DI; ST depression in leads V1 and V2, ST
      elevation in lead DIII > DII, ST depression in V3/ST elevation in DIII ratio >
      1.2 (classical criteria) and ST depression in lead aVR. ST-segment elevation or
      depression was measured 0.06 sec after the J point. RESULTS: 53 patients were
      included (mean age 59.1 +/- 13.9 years, 38 males). The RCA was the IRA in 38
      patients and the LCx in 15. Baseline characteristics (age, gender, TIMI flow,
      Killip class, and pain-to-balloon time) were similar in both groups. All the
      classical criteria were able to identify the IRA. The new criterion--ST
      depression in lead aVR--identified the IRA in a small number of patients
      (sensitivity 33%, specificity 71%, p = NS). CONCLUSIONS: The 4 classical criteria
      were useful in identifying the IRA in patients with inferior MI. ST depression in
      lead aVR (a recently proposed new criterion), on the other hand, showed limited
      utility in differentiating between RCA and LCx.

PMID- 15478323
TI  - The ups and downs of the electrocardiogram for identification of the infarct
      related artery.

PMID- 15478324
TI  - Comparative value of BNP and NT-proBNP in diagnosis of heart failure.
AB  - Heart failure (HF) remains a major diagnostic challenge. Brain natriuretic
      peptide (BNP) and the N-terminal portion of proBNP (NT-proBNP) have emerged as
      excellent diagnostic biohumoral indicators in cardiac disease. It is not clear
      which of the two is superior as a diagnostic marker in HF. OBJECTIVE: To compare
      the ability of BNP and NT-proBNP to distinguish subjects with HF from healthy
      volunteers, as well as to differentiate between HF with left ventricular (LV)
      systolic dysfunction (SD) and HF with preserved systolic function (PSF). METHODS:
      We measured plasma BNP (Shionogi, Osaka) and NT-proBNP (ELECSYS) in 21 healthy
      individuals (control group [CG]), 11 men, 10 women, mean age 54.4 +/- 11.6 years,
      with normal ECG and chest X-ray, and in 86 HF patients (HFG), 48 men, 38 women,
      mean age 71 +/- 11 years, in NYHA II-IV, fulfilling the European Society of
      Cardiology guidelines: 60 had HF with SD (SDG), ejection fraction (EF) < 40%, and
      26 had HF and PSF (PFG), EF > 40%, increased LV mass index and/or dilated left
      atrium. BNP and NT-proBNP mean and median values were compared and the
      correlation between the 2 peptides was established. For each peptide sensitivity
      (sens), specificity (spec) 93.7%, positive predictive value (PPV) 75.5% and
      negative predictive value (NPV) were calculated. Areas under the ROC curve (AUC)
      were determined for each group vs. CG and for SDG vs. PFG. RESULTS: Levels of BNP
      and NT-proBNP were significantly higher in HF patients, particularly in the SDG,
      than in healthy subjects. There was reasonable agreement between BNP and NT
      proBNP. For BNP, AUC were: HFG vs. CG: 97.7-98.0%; SDG vs. CG: 98.6-99.1%; PFG
      vs. CG: 95.1-95.9%; PFG vs. SDG: 69.7-70.9%; and for NT-proBNP: HFG vs. CG: 99.2
      99.3%; SDG vs. CG: 99.6-99.7%; PFG vs. CG: 98.3-98.5%; PFG vs. SDG: 63.3-63.6%.
      For a cut-off of 32 pg/ml, BNP has 91.7% sens, 93.7% spec, 75.5% PPV and 98.3%
      NPV. A NT-proBNP cut-off of 126 pg/ml has 96.3% sens, 98.8% spec, 94.3% PPV and
      99.3% NPV. CONCLUSIONS: Both peptides had an excellent ability to distinguish HF
      from non-HF subjects. NT-proBNP was more sensitive and specific. Nevertheless,
      neither peptide could differentiate between the SDG and the PFG by itself. NT
      proBNP is a simple, highly effective diagnostic test for HF. A favorable impact
      on management and costs is expected from implementation of this diagnostic test
      in clinical practice.

PMID- 15478325
TI  - Congenitally corrected transposition of the great arteries and aortic coarctation
      -an uncommon association.
AB  - Congenitally corrected transposition of the great arteries, L-TGA, is a rare
      abnormality accounting for less than 0.5% of clinically apparent congenital heart
      disease. Age at time of diagnosis and survival rate are variable and depend
      mostly on associated anomalies. The authors present a clinical case of a twenty
      four-year-old woman in whom, in a routine echocardiogram, congenitally corrected
      transposition of the great arteries and aortic coarctation were diagnosed, an
      unusual association. They describe the results of complementary exams
      (echocardiography, chest X-ray, electrocardiogram and cardiac angiography) that
      they believe to be useful for the correct diagnosis of this clinical situation.
      Additionally, the authors make a brief review of the literature relevant to the
      case.

PMID- 15478326
TI  - The clinical role of natriuretic peptides--importance of BNP and NT-proBNP.
      Implications in heart failure and acute coronary syndrome.
AB  - Natriuretic peptides are increasingly used as biomarkers for several clinical
      entities. An overview of the clinical applications of brain natriuretic peptide
      (BNP) and N-terminal brain natriuretic peptide (NT-proBNP) is presented. These
      neurohormones are used for diagnosis, monitoring and predicting prognosis in
      patients with chronic heart failure. The indications extend to risk
      stratification and prognosis of acute coronary syndromes and prognosis of acute
      pulmonary embolism. An appraisal of the influence of beta-blockers and other
      drugs in the measurement of natriuretic peptides is performed. The clinical
      effectiveness of treatment with the cardiac hormone nesiritide (human B-type
      natriuretic peptide) in heart failure is assessed.

PMID- 15478327
TI  - Costs of illness due to hypeercholesterolemia in Portugal.
AB  - Cardiovascular diseases are the main cause of death in Portugal, in developed
      countries and, indeed, worldwide. Hypercholesterolemia is a major risk factor for
      these diseases, including ischemic heart disease, cerebrovascular disease, and
      peripheral vascular disease. This paper reports the results of a study of the
      cost of illness associated with hypercholesterolemia and the costs directly
      attributable to hypercholesterolemia in Portugal, estimated from data for the
      year 2000. The results indicate that the cost of the health care provided to deal
      with illnesses associated with hypercholesterolemia was Euros 735.9 million
      (direct costs) and the costs of lost production due to disability of patients of
      working age was Euros 74.82 million (indirect costs). The costs attributable to
      hypercholesterolemia, those that would be avoided if hypercholesterolemia were
      completely eliminated, amount to Euros 358.84 million in direct costs and Euros
      28.31 million in indirect costs. These results confirm that hypercholesterolemia
      is a source of major health costs. This means that hypercholesterolemia deserves
      special attention from those who formulate health policy and should be given
      priority in implementing such policies.

PMID- 15478328
TI  - Unusual presentation of hypertrophic cardiomyopathy.

PMID- 15478329
TI  - Echocardiographic diagnosis of partial obstruction of modified Blalock-Taussing
      shunt.

PMID- 15478330
TI  - Sugar-sensitive thin films composed of concanavalin A and glycogen.
AB  - Sugar-sensitive thin films were prepared by a layer-by-layer deposition of
      concanavalin A (Con A) and glycogen on the surface of a quartz slide and their
      sugar-induced decomposition was studied. The Con A/glycogen multilayer films can
      be decomposed by exposing them to sugar solutions (D-glucose, D-mannose, methyl
      alpha-D-glucose and methyl-alpha-D-mannose), as a result of displacement of sugar
      residues of glycogen from the binding sites of Con A by the free sugar added in
      the solution. The rate of decomposition significantly depended on the type of
      sugar and its concentration.

PMID- 15478331
TI  - Ferritin immunosensing on microfabricated electrodes based on the integration of
      immunoprecipitation and electrochemical signaling reactions.
AB  - A signal registration strategy from micropatterned immunosensors that converts
      antigen-antibody binding reactions into electrochemical signals was demonstrated.
      An array-type micropatterned gold electrode on a silicon wafer was fabricated,
      containing two electrode geometries of rectangular (100 microm x 500 microm) and
      circular (r. 50 microm) types, exhibiting electrochemical characteristics of bulk
      and micro-electrodes, respectively. Ferritin was employed as a model analyte for
      immunosensing because it has an advantageous molecular structure for
      functionalization to the sensing interface, and is regarded as a general marker
      protein for tumors and cancer recurrence. With the fabricated and ferritin
      functionalized immunosensors, biospecific interactions were performed with
      antiferritin antiserum and secondary antibody samples, followed by
      electrochemical signaling via an immunoprecipitation reaction by the label
      enzyme. Under the optimized affinity-surface construction steps and reaction
      conditions, both types of microfabricated electrodes exhibited well-defined
      calibration results as a function of the protein concentration in antiserum
      samples. Furthermore, circular-type micropatterned immunoelectrodes exhibited
      voltammetric characteristics of microelectrodes, which is advantageous in terms
      of sensor operation under a fixed potential and low signal drift during the
      signaling reaction compared with the bulk-type electrodes. The results support
      that the employed signaling method with the proposed immunosensor configuration
      is fit for sensor miniaturization and integration to future biomicrosystems.

PMID- 15478332
TI  - Enhancement of the protein loading density by a pre-cleaning process of a gold
      substrate: confocal laser scanning microscopic study.
AB  - The immobilization of glucose oxidase (GOx), using self assembled monolayers
      (SAMs) on gold surfaces, was investigated by grazing angle FT-IR spectroscopy,
      surface plasmon resonance (SPR) spectroscopy, and atomic force microscopy (AFM)
      in conjunction with confocal laser scanning microscopy (CLSM). To find an optimum
      condition for the maximum GOx loading density on gold surfaces, different
      cleaning protocols were examined. The loading density of GOx on surfaces was
      investigated by AFM and CLSM. In particular, CLSM was more effective for
      identifying the GOx density than AFM, since its scanning speed is much faster and
      it covers a larger area. Based on CLSM images of the GOx immobilized on the
      surfaces, it was concluded that the pre-cleaning process of gold substrates using
      different solvents, such as acetone, ethanol and 2-propanol, is very important
      for enhancing the GOx loading density. This result enables us to investigate an
      effective fabrication process in fabricating biosensors.

PMID- 15478333
TI  - The upper limit pH in the dye-binding method for the determination of serum
      protein via measurements of the absorbance increase produced by protein error.
AB  - In the dye-binding method for determining the albumin concentration, the
      absorbance increase due to the change of the color shade by protein error of a pH
      indicator can be measured by a spectrophotometer. This absorbance increase is
      observed only in a restricted pH region, but this pH region is not theoretically
      studied yet. Thus, the author investigated the upper limit pH (pHUL) at which the
      absorbance increase occurs by the theoretical calculation, and compared these
      results with those obtained experimentally using four pH indicators. The pHUL is
      not affected by the dye or protein concentrations, or by the formation constant
      of the dye-protein complex; but the value changes according to the acid
      dissociation constant of the dye (KD) and the ratio of the molar absorptivities
      of the proton-dissociated dye anion (epsilonD) and the dye-protein complex
      (epsilonPD). The pHUL value can be calculated by the equation, found
      theoretically. The calculated pHUL values of BPB, BCG, BCP and BTB were 5.1, 4.8,
      6.2 and 5.5, respectively. These values correlated with the experimental results
      of 4.5 for BPB, 4.7 for BCG, 5.9 for BCP and 5.2 for BTB, but were not associated
      with the pKD values of each dye. The pHUL of these dyes did not change
      significantly for various dye and protein concentrations, as was expected from
      the thoretical calculation.

PMID- 15478334
TI  - Silica-hemin composite nanoparticles as new biocatalyst to highly sensitive
      determination of glucose in human serum.
AB  - The preparation and utilization of a novel composite silica-hemin nanoparticles
      (CSHNs) as mimetic peroxidase are reported in this article. Experimental results
      showed that the composite nanoparticles had unique advantages over free hemin
      molecules in good stability and highly catalytic activity. By employing these
      nanoparticles as biocatalyst, we developed a new spectrofluorometric method for
      the determination of trace level glucose. The calibration graph for glucose was
      linear over the range 4.0 x 10(-7) mol/L - 7.0 x 10(-5) mol/L, with a detection
      limit of 1.0 x 10(-7) mol/L. The proposed method has been successfully applied to
      the determination of glucose in serum samples and offers the advantages of being
      rapid, stable, sensitive, and renewable.

PMID- 15478335
TI  - An electrochemical biosensor for nitric oxide based on silver nanoparticles and
      hemoglobin.
AB  - A nitric oxide (NO) biosensor based on silver nanoparticles was fabricated with
      high sensitivity and selectivity as well as stability. Silver nanoparticles could
      preserve the microstructures of hemoglobin, but the electrochemical reactivity of
      the protein and its detection sensitivity toward NO could be greatly enhanced.
      Accordingly, a NO biosensor was developed. The linear concentration range was
      from 1.0 x 10(-6) to 5.0 x 10(-5) M. Its detection limit was 3.0 x 10(-7) M with
      a sensitivity of 0.0424 microA microM(-1) NO. The possible co-existing compounds
      would not interfere with the detection.

PMID- 15478336
TI  - Amperometric hydrogen peroxide biosensor based on horseradish peroxidase-labeled
      nano-Au colloids immobilized on poly(2,6-pyridinedicarboxylic acid) layer by
      cysteamine.
AB  - A sensitive hydrogen peroxidase (H2O2) amperometric sensor based on horseradish
      peroxidase (HRP)-labeled nano-Au colloids has been proposed. Nano-Au colloids
      were immobilized by the thiol group of cysteamine, which was associated with the
      carboxyl groups of poly(2,6-pyridinedicarboxylic acid) (PPDA). With the aid of
      the hydroquinone, the sensor displayed excellent electrocatalytical response to
      the reduction of H2O2. Compared with the non-Au-colloid modified electrode, i.e.,
      PPDA/HRP, the Au-colloid modified electrode exhibited better performance
      characteristics, including stability, reproducibility, sensitivity and accuracy.
      The biosensor shows a linear response to H2O2 in the range of 3.0 x 10(-7) - 2 x
      10(-3) M. The detection limit was 1.0 x 10(-7) M.

PMID- 15478337
TI  - Scanning electrochemical microscopic study of hydrogen oxidation and evolution at
      electrochemically deposited pt nanoparticulate electrode incorporated in
      polyaniline.
AB  - Scanning Electrochemical Microscopy (SECM) feedback mode and substrate generation
      tip collection (SG-TC) mode coupled with chronoamperometric approach were used to
      investigate H2 oxidation and hydrogen evolution reaction (HER) at a polyaniline
      (PAni) coated highly oriented pyrolytic graphite (HOPG) electrode. Using the
      former mode, the heterogeneous electron transfer (ET) kinetics for H2 oxidation
      was studied, while the latter mode allowed mapping of the distribution of local
      [H2] at the nanoparticulate/aqueous interface, followed by monitoring the
      transients at the tip. These preliminary studies demonstrate that SECM is useful
      in evaluating the activity of nanophase electrocatalysts. Particularly, if one
      employs nanometer-sized tips or hydrodynamic microjet electrodes where the mass
      transfer rate is significantly high, it should be possible to investigate the ET
      kinetics more accurately.

PMID- 15478338
TI  - Data processing method for the determination of accurate molecular weight
      distribution of polymers by SEC/MALDI-MS.
AB  - A novel data processing method for a hyphenated technique, size exclusion
      chromatography/matrix-assisted laser desorption/ionization-mass spectrometry
      (SEC/MALDI-MS), has been proposed to determine accurate molecular weight
      distributions on the basis of the individual oligomer species of a polymer. This
      method is based on the concept that the individual peak intensities of MALDI mass
      spectrum observed for every SEC fraction with narrow molecular weight
      distribution could be adjusted to the quantified values to reveal the accurate
      molecular weight distribution using the signal intensity of the corresponding
      fraction on the SEC chromatogram observed with a refractive index detector. At
      first, the theory of the proposed date processing is described in detail. Then,
      experimental verification of the method is described. This was performed through
      the characterization of mixtures of three kinds of monodispersed polystyrene
      reference materials (weight average molecular weight = ca. 6000, 10000, and
      18000) as model samples. An accurate trimodal molecular weight distribution for
      the individual oligomer species of the sample was obtained without any influence
      of the chromatographic band broadening observed in the original SEC chromatogram.
      Moreover, the method for depicting the elution profiles of individual oligomer
      species during SEC separation was also obtained as a "mass chromatogram" using
      the data processing procedure.

PMID- 15478339
TI  - Multi-element analysis of saline matrices by inductively coupled plasma mass
      spectrometry following on-line preconcentration using a knotted reactor.
AB  - A versatile preconcentration system for trace element determination by ICPMS was
      developed. It is composed of a commercial flow injection analysis system (FIAS)
      retrofitted with a home-made control unit containing three solenoid valves and
      working concomitantly with the FIAS, permitting selection and segmentation of
      sample, reagent, washing solution and elution flow. The knotted reactor used had
      a length of 200 cm and was made from 0.05 cm i.d. PTFE tubing. The method applies
      ammonium 1-pyrrolidinedithiocarbamate (APDC) as complexant, allowing the
      preconcentration and quantitative multi-element determination of Cu, Ni, V, Co,
      Nb, Mo, In, Sb and Bi. Ethanol and 4-methyl-2-pentanone were tested as eluents.
      Recovery tests using complex matrices and spike concentrations of 200 ng L(-1)
      showed typical values in the range of 90% to 110%. Relative standard deviations
      were < 7% for elution with ethanol and < 5% with methyl isobutyl ketone. For
      simulated freshwater samples using 4-methyl-2-pentanone as an eluent, a sample
      loading rate of 5.0 ml min(-1), and a preconcentration time of 60 s, detection
      limits (ng L(-1)) were in the range of 0.02 (Bi) to 30 (Cu). Under these
      conditions, analytical frequency was about 15 samples per hour. The feasibility
      of the method was demonstrated by the succesful analysis of wastewater and
      seawater certified reference materials.

PMID- 15478340
TI  - Distribution pattern of rare earth ions between water and montmorillonite and its
      relation to the sorbed species of the ions.
AB  - REE (rare earth element) distribution coefficients (Kd) between the aqueous phase
      and montmorillonite surface were obtained to investigate the relation between the
      REE distribution patterns and the species of REE sorbed on the solid-water
      interface. It was shown that the features in the REE patterns, such as the slope
      of the REE patterns, the tetrad effect, and the Y/Ho ratio, were closely related
      to the REE species at the montmorillonite-water interface. In a binary system
      (REE-montmorillonite) below pH 5, three features (a larger Kd value for a lighter
      REE, the absence of the tetrad effect, and the Y/Ho ratio being unchanged from
      its initial value) suggest that hydrated REE are directly sorbed as an outer
      sphere complex at the montmorillonite-water interface. Above pH 5.5, the features
      in the REE patterns, the larger Kd value for heavier REE, the M-type tetrad
      effect, and the reduced Y/Ho ratio, showed the formation of an inner-sphere
      complex of REE with -OH group at the montmorillonite surface. In addition, the
      REE patterns in the presence of humic acid at pH 5.9 were also studied, where the
      REE patterns became flat, suggesting that the humate complex is dominant as both
      dissolved and sorbed species of REE in the ternary system. All of these results
      were consistent with the spectroscopic data (laser-induced fluorescence
      spectroscopy) showing the local structure of Eu(III) conducted in the same
      experimental system. The present results suggest that the features in the REE
      distribution patterns include information on the REE species at the solid-water
      interface.

PMID- 15478341
TI  - A rapid HPLC assay for the simultaneous determination of propafenone and its
      major metabolites in human serum.
AB  - A rapid and specific HPLC method has been developed and validated for the
      simultaneous determination of propafenone, an antiarrhythmic agent, and its major
      metabolites in human serum. The sample preparation was a simple deproteinization
      with a mixture of ZnSO4 and methanol, yielding almost 100% recoveries of three
      compounds. Separation was developed on a reverse-phase tracer excel C18 column
      (25 x 0.46 cm i.d., 5 microm), using an acetonitrile-phosphate buffer gradient at
      a flow rate of 1.7 ml min(-1), and UV detection of 210 nm. The calibration curves
      were linear (r2 > 0.999) in the concentration range of 10 - 750 ng ml(-1). The
      lower limit of quantification was 10 ng ml(-1) for all of the compounds studied.
      The within and between day precisions in the measurement of QC samples at four
      tested concentrations were in the range of 1.4 - 8.1% and 4.2 - 11.5% RSD,
      respectively. The developed procedure was applied to assess the pharmacokinetics
      of propafenone and its major metabolites following administration of a single 300
      mg oral dose of propafenone hydrochloride to three healthy male volunteers.

PMID- 15478342
TI  - Phosphopeptide-selective column-switching RP-HPLC with a titania precolumn.
AB  - A methodology of phosphopeptide-selective analysis coupled with column-switching
      HPLC utilizing titania as precolumn media is presented. Phosphopeptides were
      selectively enriched on titania packing within a protein/peptide mixture without
      any additional procedure, and analyzed by column-switching high-performance
      liquid chromatography. First, phospho-compounds were separated from complex
      mixtures by trapping them under acidic conditions on a titania packing, where non
      phosphorylated compounds were effused out of the precolumn. Subsequently, phospho
      compounds were desorbed from the titania column under a specific condition and
      analyzed. The behavior of phospho-compounds on a titania surface, especially
      adsorption/desorption, was precisely examined and optimized. A phosphoric buffer
      was successively employed for the elution of phosphopeptides on a titania surface
      by competition with the free phosphate group. From the successes of a selective
      concentration/analysis of phosphopeptides with column-switching HPLC with a
      titania precolumn, a novel phosphopeptide-selective RP-HPLC analysis has been
      shown to have an application possibility as a tool for phosphoproteomics.

PMID- 15478343
TI  - Estimation of trace amounts of chromium(III) in multi-vitamin with multi-mineral
      formulations.
AB  - Two new specific, selective, simple and inexpensive spectroscopic methods for
      estimating a trace amount of chromium (Cr3+) from a multi-vitamin with multi
      mineral pharmaceutical formulations were developed. The proposed methods are
      based on the conversion of Cr3+ to Cr6+ either by oxidation with a nitric acid
      perchloric acid mixture (method I) or by fusion with an excess amount of sodium
      carbonate (method II), followed by the complexation of Cr6+ with 1,5
      diphenylcarbazide (DPC) in a mineral acidic solution of pH 1.0 +/- 0.5. The pink
      colored complex was estimated at 544 nm. Both methods were found to be linear in
      the range of 0.1 - 0.8 microg/ml with a limit of detection in the range of 0.0123
      - 0.0157 microg/ml and a limit of quantitation in the range of 0.0419 - 0.0525
      microg/ml. Method I was found to be suitable for estimating Cr3+ species in
      various formulations, like tablets, capsules and syrups, while method II was
      found to be suitable for tablets and capsules. Satisfactory recovery from spiked
      samples of standard Cr3+ suggests no interference of any excipients and diverse
      ions present in the formulations. The developed methods were compared with AAS by
      ANOVA, and no significant difference was observed.

PMID- 15478344
TI  - Time-resolved chemiluminescence technique for the microdetermination of proteins
      based on their complexation with copper(II).
AB  - Based on the complexation between proteins and Cu(II) coupled with the time
      resolved chemiluminescence (CL) technique, a highly sensitive and quantitative
      assay for measuring proteins in solution is described. The complexes of proteins
      with Cu(II) have a strongly catalytic effect on the luminol-H2O2 CL reaction.
      Because the CL emission produced by the complexes is much more long-lived than
      that by Cu(II), the CL signals originating from proteins can be easily identified
      and measured with a time-resolved technique. On this basis, bovine albumin
      fraction V (BAF V) can be quantitatively determined in the range of 0.01 - 5.0
      microg/ml with a detection limit of 5.8 ng/ml. The results show that the proposed
      assay exhibits a small variation in the response values for the same amount of
      different proteins, as compared to the Lowry as well as Bradford assays. The CL
      assay has also been studied for the detection of immobilized proteins.

PMID- 15478345
TI  - Spectrophotometric studies of the interaction of noble metals with quercetin and
      quercetin-5'-sulfonic acid.
AB  - Results of some studies on the interaction of noble metals with quercetin (Q) and
      quercetin-5'-sulfonic acid (QSA), the compounds of flavonoid group, are
      presented. The reactions of chloride complexes of the metals: RuOHCl5(2-),
      PdCl4(2-), OsCl6(2-), PtCl6(2-) and AuCl4- with both reagents were examined. The
      redox reactions of ruthenium and gold with Q and QSA have been identified. The
      reaction of the metals with both reagents results in the formation of the
      oxidized form of Q that exhibits maximum absorbance at 291 nm. Ruthenium and gold
      react with the examined reagents under similar conditions: 0.04 M HCl and 1 x 10(
      4) M Q (or QSA). The CH3OH + H2O (1:1) (Q) and pure aqueous (QSA) media can be
      used. The reaction of gold with Q is slow at room temperature. It can be
      accelerated by heating the solution being examined. The reaction proceeds
      significantly faster when the water-soluble sulfonic derivative of quercetin,
      quercetin-5'-sulfonic acid, is used as a reagent. The new species formed can make
      the basis of spectrophotometric methods for the determination of ruthenium and
      gold. The molar absorptivities at 291 nm are equal to 5.0 x 10(3) and 2.2 x 10(4)
      L mol(-1) cm(-1) for Ru and Au, respectively, independently of the reagent used.
      Some methods for the determination of the content of gold (0.04%) in a cosmetic
      cream were developed.

PMID- 15478347
TI  - Surface-enhanced Raman scattering from oleate-stabilized silver colloids at a
      liquid/liquid interface.
AB  - Oleate-stabilized silver colloids of 5-nm-diameter were adsorbed to a
      toluene/water interface, and surface enhanced Raman scattering (SERS) spectra
      from these colloids were measured under the total internal reflection (TIR)
      condition. From the observed spectra, we examined the states of oleate ions and
      toluene molecules on silver colloids at the liquid/liquid interfacial region. The
      TIR-SERS spectra of oleate ions showed stronger peaks of the carboxylate group
      and the ethylene group than those of alkyl chains. From these results, it was
      found that the oleate ions were adsorbed on the silver surface in two different
      ways at the liquid/liquid interface; the carboxylate group adsorbed in the
      organic phase side, while the ethylene group adsorbed in the aqueous phase side.
      The shifts of the toluene in the interfacial SERS spectra were identical to those
      of bulk toluene, though the relative intensities among the peaks were not same.
      This result suggested that the toluene was adsorbed with a weak interaction, but
      was significantly enhanced by the local electromagnetic field at the colloid
      surface.

PMID- 15478346
TI  - Removal of interference signals due to water from in vivo near-infrared (NIR)
      spectra of blood glucose by region orthogonal signal correction (ROSC).
AB  - A novel chemometric method, region orthogonal signal correction (ROSC), is
      proposed and applied to pretreat near-infrared (NIR) spectra of blood glucose
      measured in vivo. Water is the most serious interference component in such kinds
      of noninvasive measurements, because it shows very high absorbance in the
      spectra. In the present study, the spectra of blood glucose in the range of 1212 
      1889 nm are used, in which the absorption of water around 1440 nm is very high.
      ROSC aims at removing the interference signal due to water from the spectra by
      selecting a set of spectra with a special region of 1404 - 1454 nm that mainly
      contain information about the variation of the interference component, water, and
      calculating the orthogonal components to the concentrations of glucose that will
      be removed. The difference between ROSC and orthogonal signal correction (OSC) is
      that ROSC uses a special region of spectra for the estimation of scores and
      loading weights of orthogonal components to pretreat the spectra in other
      regions, while OSC only uses one fixed region of spectra to calculate loadings,
      scores and weights of OSC components and removes the OSC components in the same
      region. A clear advantage of ROSC is that it is more interpretable than OSC,
      because one can select a spectral region to remove the variation of a special
      component such as water. Another chemometric method, moving window partial least
      squares (MWPLSR), is also used to select informative regions of glucose from the
      NIR spectra of blood glucose measured in vivo, leading to improved PLS models.
      Results of the application of ROSC demonstrate that ROSC-pretreated spectra
      including the whole spectral region of 1212 - 1889 nm or an informative region of
      1600- 1730 nm selected by MWPLSR provide very good performance of the PLS models.
      Especially, the later region yields a model with RMSECV of 15.8911 mg/dL for four
      PLS components. ROSC is a potential chemometric technique in the pretreatment of
      various spectra.

PMID- 15478348
TI  - Cloud point extraction and preconcentration for the gas chromatography of
      phenothiazine tranquilizers in spiked human serum.
AB  - Cloud point extraction was successfully applied to the preconcentration of
      phenothiazine derivatives, such as pericyazine (PC), chlorpromazine (CP) and
      fluphenazine (FUL), for gas chromatography (GC). Phenothiazine derivatives were
      separated from surfactants by passing the surfactant-rich phase through a cation
      exchange column after cloud point extraction, permitting the determination of the
      phenothiazine derivatives extracted in the surfactant-rich phase by GC. The
      optimal condition for the cloud point extraction of phenothiazine derivatives was
      also investigated using Triton X-100, Triton X-114, and PONPE10. Triton X-114
      provided the most efficient recovery of phenothiazine derivatives among the
      surfactants used. The addition of sodium chloride and excess ammonia to the
      sample solution resulted in a decrement of the recovery of the phenothiazine
      derivatives. The proposed method was applied to the determination of
      phenothiazine derivatives in spiked human serum by GC. The recoveries of PC, CP,
      and FUL in spiked human serum were 95.1%, 87.1%, and 84.7%, respectively.

PMID- 15478349
TI  - Alumina-based fiber for solid phase microextraction of alcohols from gaseous
      samples.
AB  - On the basis of the affinity of alumina towards hydroxyl functional groups, a
      solid phase microextraction (SPME) fiber was constructed using alumina powder and
      poly(vinyl chloride) (PVC). Different compositions were tested and alumina:PVC
      (97:3) was selected as an optimun composition. A piece of silver wire was used as
      fiber support. The fiber producing was simple and could be completed in a few
      minutes. The mechanical durability of the fiber was so good that only a single
      fiber was used during this study. Ethanol, 1-butanol, 2-butanol, 1-pentanol, 2
      pentanol and cyclohexanol were selected as target analytes. Finally, ethanol
      concentration in the fruit juices and vinegar was measured using SPME-capillary
      gas chromatography followed by flame ionization detection.

PMID- 15478350
TI  - Sensitivity enhancement in flame atomic absorption spectrometry for determination
      of copper in human thyroid tissues.
AB  - Various designs of quartz tube in a slotted tube atom trap were examined for
      improving the sensitivity of flame AAS. A 3.5-fold enhancement in the sensitivity
      was obtained by using the optimized method. The method was applied to the
      determination of Cu in cancerous and non-cancerous human thyroid tissues. The Cu
      concentrations of the cancerous samples tended to increase compared with the non
      cancerous samples. Zn concentrations of the same tissues were also determined.

PMID- 15478351
TI  - Preconcentration of mercury using duolite GT-73 in the analysis of water samples
      by inductively coupled plasma atomic emission spectrometry.
AB  - Duolite GT-73 resin was used for the preconcentration of Hg(II) from hydrochloric
      acid media as well as separation of the analyte from diversity of the co-existing
      metal ions (Al, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb and Zn) in off-line column
      operation. Due to the high affinity of the resin to the transition metals, Hg was
      adsorbed alongside with the foreign metals investigated. A complete release of
      the concomitant metals from the resin without the desorption of Hg was carried
      out using solutions of HCl and HNO3. A quantitative recovery of Hg was obtained
      by digestion of the resin using a H2SO4 and H2O2 mixture in an open-vessel
      system. An enrichment factor of 40 was achieved. The devised procedure was
      applied for the determination of Hg(II) in tap-water samples.

PMID- 15478352
TI  - Classes and functions of Listeria monocytogenes surface proteins.
AB  - Listeria monocytogenes is an opportunistic pathogen that causes infections
      collectively termed listeriosis, which are related to the ingestion of food
      contaminated with these gram-positive rods. The pathogenicity of L. monocytogenes
      is determined by the following virulence factors: listeriolysin O, protein ActA,
      two phospholipases C, internalins (In1A and In1B), protein CwhA and a
      metalloprotease. The bacterium is a model organism in studies on the pathogenesis
      of intracellular parasites. It is able to penetrate, multiply and propagate in
      various types of eukaryotic cells and is also able to overcome the three main
      barriers encountered in the host: the intestinal barrier, the blood-brain barrier
      and the placenta. Based on L. monocytogenes genome sequence analysis 133 surface
      proteins have been identified. In particular, the large number of proteins
      covalently bound to murein sets L. monocytogenes apart from other gram-positive
      bacteria. The ability of this pathogen to multiply in various environments as
      well as the possibility of its interaction with many kinds of eukaryotic cells
      is, in fact, made possible by the large number of surface proteins.

PMID- 15478353
TI  - PCR-RFLP analysis of a point mutation in codons 315 and 463 of the katG gene of
      Mycobacterium tuberculosis isolated from patients in Silesia, Poland.
AB  - Resistance to antituberculous agents is an important cause of ineffectiveness of
      antimicrobial therapy. The resistance of M. tuberculosis to antituberculous
      agents is a result of mutations in genes participating in those agent's action.
      The antituberculous drug--isoniazid can be activated by Mycobacterium
      tuberculosis either through a hydroperoxidase I/II or a superoxide-dependent
      oxyferrous pathway. The present study analyzed the frequency of the mutations
      occurring in codons 315 and 463 in katG gene of Mycobacterium tuberculosis
      strains, isolated from patients with pulmonary tuberculosis from Silesia, Poland.
      In this study 23 isoniazid-resistant Mycobacterium tuberculosis strains were
      analyzed. For RFLP analysis, a 620 bp amplified fragment of katG gene was
      digested with restriction endonuclease MspI. Among 24 isoniazid-resistant
      strains, isolated from patients between 2000-2001, point mutations were found in
      30% of analyzed isoniazid-resistant strains in codons 315 or 463 (7 strains). In
      contrast, no mutations in codons 315 and/or 463 katG gene were found in 16
      strains (70%). Obtained results suggests that point mutations S315T (AGC-->ACC)
      and R463L in katG gene are infrequent in the analyzed population.

PMID- 15478354
TI  - Human papillomavirus (HPV) and Epstein-Barr virus (EBV) cervical infections in
      women with normal and abnormal cytology.
AB  - In 48 adult women, subdivided into group 1 with no cervical intraepithelial
      neoplasia (CIN-negative) and group 2 (CIN-positive), endocervical scrapes were
      tested for the presence EBV DNA and HPV DNA using PCR-ELISA. In addition,
      attempts were made to detect HPV 16 and HPV 18 using other PCR amplification
      techniques. In parallel, in biopsies of uterine cervix obtained from group 2
      patients, presence of EBER was documented by RNA in situ hybridization (ISH).
      Sera of all patients were tested for anti-EBV antibodies. In group 1, presence of
      EBV DNA was noted in the material obtained from 8 women (30.8%), while HPV DNA
      was detected in 2 women (7.7%). In group 2, EBV DNA was present in the material
      obtained from 11 patients (50%), including 7 (31.8%) with HPV DNA also
      identified. In 5 women (22.7%) of group 2 only HPV DNA was detected. The
      identifical HPV DNA in all cases belonged to HPV 16 type. Both in group 1 and in
      group 2, all patients were found to carry serum IgG-anti-VCA and IgG-anti-EBNA
      antibodies. The results allow to conclude that, co-infection with EBV and HPV 16
      may be of cervical significance in etiopathogenesis of uterine cervical cancer.

PMID- 15478355
TI  - An attempt to protect winter wheat against Gaeumannomyces graminis var. tritici
      by the use of rhizobacteria Pseudomonas fluorescens and Bacillus mycoides.
AB  - Pseudomonas fluorescens strains III107 and II21 and Bacillus mycoides strains
      JC192 and K184, stimulating growth of winter wheat, were chosen for the studies.
      The bacterial strains inhibited on agar nutrient medium the growth of
      Gaeumannomyces graminis var. tritici (Ggt)--the pathogenic fungus causing take
      all on wheat. Both strains of pseudomonads synthesized relatively high amounts of
      Fe3+ chelators. The strains of bacilli were characterized by the very fast
      spreading on agar media. Furthermore, strain II21 was highly cyanogenic, and
      strain JC192 highly chitinolytic. Bacterization of winter wheat seeds (especially
      with strains III107 and JC192) significantly reduced the percentage of the plants
      infested with the pathogen in the 28 day glasshouse pot experiment. In the plot
      experiment, the winter wheat seeds were inoculated with a mixture of strains
      III107, II21 and JC192. Due to the bacterization the yield of wheat grain and
      straw was higher in comparison to the series with Ggt alone by 122% and 75%,
      respectively, but it amounted only to 45% and 43% of the control series not
      contaminated with Ggt. The decrease of percentage of wheat ears with weight less
      than 500 mg from 61% in Ggt-series to 25% in Ggt-bacterized-series, and
      especially the decrease of percentage of wheat ears with weight less than 200 mg
      from 43% to 14% additionally indicate the partial protection of the winter wheat
      against Ggt by the rhizobacteria. In the experimental series not contaminated
      with Ggt the percentage of these wheat ears fractions did not exceed 3% and 0.5%,
      respectively.

PMID- 15478356
TI  - Induced resistance in tomato plants by IAA against Fusarium oxysporum
      lycopersici.
AB  - The phytohormone IAA (indol-3-acetic acid) was tested in vitro on growth of
      tomato wilt pathogen Fusarium oxysporum lycopersici. The hormone reduced spore
      germination, mycelial dry weight and protein content. Such reduction was matched
      with the elevation in the hormone concentration. The in vivo application of IAA
      to soil of the uninoculated plants (controls) improved growth and yielded longer
      shoot and root, particularly at low concentrations. Moreover, the hormone could
      prevent completely any chance for disease incidence by soil pathogens. Presence
      of IAA in soil of inoculated plants not only reduced the infection rate but also
      increased plant growth, causing that they appeared healthy and normal. Disease
      suppression in tomato plants, exerted by application of IAA, was achieved through
      either increasing plant growth, exerting a direct harmful effect on the target
      pathogen and/or inducing resistance in host tissue. The induced resistance was
      correlated with induction of certain secondary metabolites which may have a role
      in increasing tolerance in tomato plants to the pathogen.

PMID- 15478357
TI  - Optimization of carbon-nitrogen ratio for production of gibberellic acid by
      Pseudomonas sp.
AB  - In this study, favorable carbon-nitrogen ratio for high yields of gibberellic
      acid (GA3) production from Pseudomonas sp. was investigated. First of all,
      optimum carbon (glucose, maltose, sucrose, fructose, lactose) and nitrogen (KNO3,
      NH4Cl, NaNO3, urea, glycine) sources among the others were chosen. The highest
      yield of GA3 productivity was found in growth medium supplemented with fructose
      (168.5 mg/L). NaNO3 was found as a suitable nitrogen source (141 mg/L). Then, in
      order to determine the optimum carbon-nitrogen ratio, different concentrations of
      carbon (from 50 mM to 150 mM) and nitrogen (from 17 mM to 47 mM) sources were
      added in culture media. As a result, optimum carbon-nitrogen ratio for GA3
      production from Pseudomonas sp. was found to be 100:17 mM.

PMID- 15478358
TI  - Influence of DnaK and DnaJ chaperones on Escherichia coli membrane lipid
      composition.
AB  - The content of fatty acids extracted from the membranes of E. coli MC 1061
      harboring the wild-type dnaKdnaJ alleles and its delta dnaJ and delta dnaKdnaJ
      derivatives was compared. It was demonstrated that dodecanoic acid was missing in
      NPLs fraction extracted from both mutants grown at 42 degrees C. Phospholipids
      extracted from mutant strains were deprived of hexadecanoic acid methyl ester and
      octadecanol, the latter being correlated with the presence of octadecanoic acid.
      The amount of LPS extracted from delta dnaKdanJ mutant was significantly lower
      when compared with wild-type strain and delta dnaJ mutant.

PMID- 15478359
TI  - The carrier state of shiga-like toxin II (SLT II) and hemolysin-producing
      enteroaggregative Escherichia coli strain.
AB  - Shiga-like toxin-producing (SLTEC) Escherichia coli strains are one of the most
      important food borne emerging pathogens. One hundred and fifty-seven E. coli
      strains isolated from 39 children with diarrhea of unknown origin and one hundred
      and five E. coli strains from 20 healthy children were examined for Shiga-like
      toxin production in Vero cell line assay. The synthesis of Shiga-like toxin was
      observed on Vero cell line and confirmed by PCR for one of 262 E. coli strains
      tested. The shiga-like toxin II-positive E. coli strain was isolated from 2-years
      old healthy child with no symptoms of gastrointestinal tract infection.

PMID- 15478360
TI  - Detection of CMV infected cells by flow cytometry--evaluation of MAbs CCH2 and
      AAC10 directed against early and late CMV antigens.
AB  - In this work evaluation of usefulness of monoclonal antibodies (MAbs) CCH2 and
      AAC10 directed against early--pUL44(DB52) and late--ppUL83(pp65) CMV antigens,
      utilized in Department of Virology, NIH for routine diagnosis of CMV infection by
      shell vial and pp65 antigenemia assay, for determination of CMV antigens by flow
      cytometry in human leucocytes, isolated, infected and cultivated in vitro was
      presented.

PMID- 15478361
TI  - Multimodality intraoperative monitoring during complex lumbosacral procedures:
      indications, techniques, and long-term follow-up review of 61 consecutive cases.
AB  - OBJECT: The purpose of this study was to examine the neurological outcomes after
      complex lumbosacral surgery in patients undergoing multimodality
      neurophysiological monitoring. METHODS: Sixty-one patients were consecutively
      enrolled in this study. These patients underwent complex intra- and extradural
      lumbosacral procedures with concomitant intraoperative electromyography (EMG)
      monitoring of the lower-limb muscles, external anal and urethral sphincters (EAS
      and EUS), and lower-limb somatosensory evoked potentials (SSEPs). Long-term
      (minimum 2-year) clinical follow-up data were obtained in all cases. Most
      patients were treated for spinal/spinal cord tumors (61%) or adult tethered cord
      syndrome (25%). Recordable lower-extremity SSEPs were reported in 54 patients
      (89%). New postoperative neurological deficits occurred in only three patients
      (4.9%), and remained persistent in only one patient (1.6%) at long-term follow-up
      examination. In only one of these cases was a significant decrease in SSEP
      amplitude detected. Spontaneous EMG activity was observed in the lower-extremity
      muscles and/or EAS and EUS in 51 cases (84%). Intraoperatively, EMG demonstrated
      activity only in the EUS in 5% of patients and only in the EAS in 28%. In seven
      patients (11%) spontaneous intraoperative EMG activity was observed in both the
      EAS and the EUS; however, in only three of these cases was EMG activity recorded
      in both sphincters simultaneously. In addition to spontaneously recorded EMG
      activity, electrically evoked EMG activity was also used as an intraoperative
      adjunct. A bipolar stimulating electrode was used to identify functional neural
      tissue before undertaking microsurgical dissection in 58 individuals (95%). In
      the majority of these patients, evoked EMG activity occurred either in one (33%)
      or in two muscles (9%) simultaneously. The presence of electrically evoked EMG
      activity in structures encountered during microdissection altered the plan of
      treatment in 24 cases (42%). CONCLUSIONS: The authors conclude that the combined
      SSEP and EMG monitoring of lower-limb muscles, EAS, and EUS is a practical and
      reliable method for obtaining optimal electrophysiological feedback during
      complex neurosurgical procedures involving the conus medullaris and cauda equina.
      Analysis of the results indicates that these intraoperative adjunctive modalities
      positively influence decision making with regard to microsurgery and reduce the
      risk of perioperative neurological complications. Validation of the clinical
      value of these approaches, however, will require further assessment in a larger
      prospective cohort of patients.

PMID- 15478362
TI  - Bone morphogenetic proteins in anterior lumbar interbody fusion: old techniques
      and new technologies. Invited submission from the Joint Section Meeting on
      Disorders of the Spine and Peripheral Nerves, March 2004.
AB  - OBJECT: The author reports the clinical and radiographic outcomes obtained in
      three prospective multicenter clinical trials in which recombinant human bone
      morphogenetic protein-2 (rhBMP-2) was used in anterior lumbar interbody fusion
      (ALIF). METHODS: Stand-alone interbody fusion cages were used, and supplemental
      fixation was not performed as part of the study protocol. Patients were randomly
      assigned to one of two ALIF groups: one in which autologous iliac crest bone
      graft was used (control) and one in which an rhBMP-2-coated absorbable collagen
      sponge was placed (investigational group). In all patients who underwent rhBMP-2
      augmented fusion, imaging demonstrated evidence of bone induction and early
      incorporation of the cortical allografts. Overall, more expedient clinical
      improvements and higher success rates were observed in the rhBMP-2 group.
      CONCLUSIONS: In these studies it was shown that rhBMP-2 is a safe and effective
      material for facilitating ALIF and for decreasing pain and improving clinical
      outcomes.

PMID- 15478363
TI  - Clinical outcomes and complications associated with pedicle screw fixation
      augmented lumbar interbody fusion.
AB  - OBJECT: The authors conducted a prospective study to evaluate the clinical and
      radiological outcomes and complications associated with uni- and bilateral
      transforaminal lumbar interbody fusion (TLIF) performed using carbon fiber
      Brantigan I/F Cages and pedicle screw fixation. METHODS: Forty-two consecutive
      patients who had undergone uni- or bilateral TLIF between February 1999 and July
      2000 were prospectively evaluated. Clinical outcome was graded using a modified
      Prolo Scale, the McGill Pain Index Scale, a follow-up questionnaire, and charts.
      An independent radiologist assessed radiological outcomes. All patients were
      followed for at least 1 year. Based on Prolo Scale scores, an excellent or good 1
      year outcome was achieved in 73% of patients; 90% of patients responded that they
      would undergo the procedure again. At 1 year, radiographic fusion was
      demonstrated in 74% and was statistically related to clinical outcome (p < 0.05).
      There were no deaths or major hardware failures. Complications requiring repeated
      surgery included one case of cerebrospinal fluid (CSF) leakage and one case in
      which the hemovac drain was retained. There were four cases involving minor wound
      infections, eight involving CSF leaks, and none requiring repeated surgery. On
      routine follow-up radiography one pedicle screw was found to be broken; the
      patient remained asymptomatic and fusion occurred. CONCLUSIONS: Unilateral and
      bilateral TLIF involving placement of carbon fiber cages and pedicle screw
      fixation are effective treatment options in patients with indications for lumbar
      arthrodesis. The procedures result in acceptable rates of fusion and clinical
      success, and a minimal incidence of morbidity when performed by an experienced
      surgeon.

PMID- 15478364
TI  - Prospective outcomes evaluation after decompression with or without instrumented
      fusion for lumbar stenosis and degenerative Grade I spondylolisthesis.
AB  - OBJECT: There is considerable debate among spine surgeons regarding whether
      fusion should be used to augment decompressive surgery in patients with
      symptomatic lumbar spinal stenosis involving Grade I degenerative
      spondylolisthesis. The authors prospectively evaluated the outcomes of patients
      treated between 2000 and 2002 at two institutions to determine whether fusion
      improves functional outcome 1 year after surgery. METHODS: Patients ranged in age
      from 50 to 81 years. They presented with degenerative Grade I (3- to 14-mm)
      spondylolisthesis and lumbar stenosis without gross instability (< 3 mm of motion
      at the level of subluxation). Those in whom previous surgery had been performed
      at the level of subluxation were excluded. Each patient completed Oswestry
      Disability Index (ODI) and Short Form-36 (SF-36) questionnaires preoperatively
      and at 6 to 12 months postoperatively. Some patients underwent decompression
      alone (20 cases), whereas others underwent decompression and posterolateral
      instrumentation-assisted fusion (14 cases), at the treating surgeon's discretion.
      Baseline demographic data, radiographic features, and ODI and SF-36 scores were
      similar in both groups. The 1-year fusion rate was 93%. Both forms of surgery
      independently improved outcome compared with baseline status, based on ODI and SF
      36 physical component summary (PCS) results (p < 0.001). Decompression combined
      with fusion led to an improvement in ODI scores of 27.5 points, whereas
      decompression alone was associated with a 13.6-point increase (p = 0.02).
      Analysis of the SF-36 PCS data also demonstrated a significant intergroup
      difference (p = 0.003). CONCLUSIONS: Surgery substantially improved 1-year
      outcomes based on established outcomes instruments in patients with Grade I
      spondylolisthesis and stenosis. Fusion was associated with greater functional
      improvement.

PMID- 15478365
TI  - Vertical atlantoaxial distraction injuries: radiological criteria and clinical
      implications.
AB  - OBJECT: The authors sought to establish radiological criteria for the diagnosis
      of C1-2 vertical distraction injuries. METHODS: Conventional radiography,
      computerized tomography (CT), and magnetic resonance (MR) imaging findings in
      five patients with a C1-2 vertical distraction injury were correlated with their
      clinical history, operative findings, and autopsy findings. The basion-dens
      interval (BDI) and the C-1 and C-2 lateral mass interval (LMI) were measured in
      93 control patients who underwent CT angiography; these measurements were used to
      define the normal BDI and LMI. The MR imaging results obtained in 30 healthy
      individuals were used to characterize the normal signal intensity of the C1-2
      joint. The MR imaging results were compared with MR images obtained in five
      patients with distraction injuries. In the 93 patients, the BDI averaged 4.7 mm
      (standard deviation [SD] 1.7 mm, range 0.6-9 mm) and the LMI averaged 1.7 mm (SD
      0.48 mm, range 0.7-3.3 mm). Based on CT scanning in the five patients with
      distraction injuries, the BDIs (mean 11.9 mm, SD 3.2 mm; p < 0.001) and LMIs
      (mean 5.5 mm, SD 2 mm; p < 0.0001) were significantly greater than in the control
      group. Fast-spin echo inversion-recovery MR images obtained in these five
      patients revealed markedly increased signal distributed throughout the C1-2
      lateral mass articulations bilaterally. CONCLUSIONS: In 95% of healthy
      individuals, the LMI ranged between 0.7 and 2.6 mm. An LMI greater than 2.6 mm
      indicates the possibility of a distraction injury, which can be confirmed using
      MR imaging. Patients with a suspected C1-2 distraction injury may be candidates
      for surgical fusion of C1-2.

PMID- 15478366
TI  - Treatment of basilar invagination by atlantoaxial joint distraction and direct
      lateral mass fixation.
AB  - OBJECT: The author discusses the successful preliminary experience of treating
      selected cases of basilar invagination by performing atlantoaxial joint
      distraction, reduction of the basilar invagination, and direct lateral mass
      atlantoaxial plate/screw fixation. METHODS: Twenty-two patients with basilar
      invagination-in which the odontoid process invaginated into the foramen magnum
      and the tip of the odontoid process was above the Chamberlain, McRae foramen
      magnum, and Wackenheim clival lines-were selected to undergo surgery. In all
      patients fixed atlantoaxial dislocations were documented. The 16 male and six
      female patients ranged in age from 8 to 50 years. A history of trauma prior to
      the onset of symptoms was documented in 17 patients. Following surgery, the
      author observed minimal-to-significant reduction of basilar invagination and
      alteration in other craniospinal parameters resulting in restoration of alignment
      of the tip of the odontoid process and the clivus and the entire craniovertebral
      junction in all patients. In addition to neurological and radiological
      improvement, preoperative symptoms of torticollis resolved significantly in all
      patients. The minimum follow-up period was 12 months and the mean was 28 months.
      CONCLUSIONS: Joint distraction and firm lateral mass fixation in selected cases
      of basilar invagination is a reasonable surgical treatment for reducing the
      basilar invagination, restoring craniospinal alignment, and establishing fixation
      of the atlantoaxial joint.

PMID- 15478367
TI  - Single-stage posterolateral transpedicular approach for resection of epidural
      metastatic spine tumors involving the vertebral body with circumferential
      reconstruction: results in 140 patients. Invited submission from the Joint
      Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004.
AB  - OBJECT: Patients with metastatic spine tumors often have multicolumn involvement
      and high-grade epidural compression, requiring circumferential decompression and
      instrumentation. Secondary medical and oncological issues add morbidity to
      combined approaches. The authors present their experience in using the single
      stage posterolateral transpedicular approach (PTA) to decompress the spine
      circumferentially and to place instrumentation. METHODS: From September 1997 to
      February 2004, 140 patients with spine metastases underwent the PTA. Magnetic
      resonance imaging revealed high-grade spinal cord compression in 120 patients
      (86%) and lytic vertebral body destruction in all patients. Preoperatively 84
      patients (60%) received radiotherapy directed to the involved level and 42 (30%)
      underwent tumor embolization. Following circumferential decompression, all
      patients underwent anterior reconstruction with polymethylmethacrylate and
      Steinmann pins, and posterior segmental fixation. The median operative time was
      5.1 hours, the median blood loss was 1500 ml, and the median hospital stay was 9
      days. Ninety-six percent of the patients experienced postoperative pain
      improvement and improvement in or stabilization of neurological status. In 51
      nonambulatory patients with poor Eastern Cooperative Oncology Group grades, 75%
      regained the ability to walk. One month postoperatively 90% of patients achieved
      good-to-excellent performance scores. The overall median patient survival time
      was 7.7 months. Patients with colon and lung carcinomas had significantly shorter
      survival times. Major operative complications occurred in 20 patients (14.3%).
      Wound complications occurred in 16 patients (11.4%), but this was not correlated
      with preoperative radiation treatment. CONCLUSIONS: The PTA allows
      circumferential epidural tumor decompression and the placement of anterior and
      posterior spinal column instrumention. Immediate spinal stability is achieved
      without the use of brace therapy. This technique achieved a high success rate for
      pain palliation, neurological preservation, and functional improvement, while
      avoiding the morbidity associated with combined approaches.

PMID- 15478368
TI  - The V2 segment of the vertebral artery and its branches.
AB  - OBJECT: The goal of this study was to demonstrate the origins, courses,
      anastomoses, and target tissues of the arterial branches that arise from the V2
      segment of the vertebral artery. METHODS: Ten adult cadaveric necks (20 V2
      segment specimens) were examined (magnification x 40) after injection of colored
      silicon. The branches at each cervical level were classified in a new system
      according to anatomical features and target tissues-anterior, posterior, medial,
      and lateral. Incidence with which each branch category was observed at each
      cervical level was calculated. Anterior branches were observed at C-3 in all 20
      V2 segment specimens. The incidence with which the posterior branch was present
      at C-4 was 45%, whereas the corresponding rates at segments superior and inferior
      were lower. The medial V2 segment branches were assessed in four subcategories.
      The anterior spinal artery was present at C-3 in all specimens, whereas the mean
      incidence at the C4-6 level was 46.7%. The posterior spinal artery was most
      frequently detected at C-3 (60%). The anterior radicular artery (RA) was present
      at C-5 in 50% of the specimens, whereas the posterior RA was detected at C-5 in
      only 35%. Lateral branches were most frequently detected at C-3. CONCLUSIONS: The
      authors provide detailed anatomical information about the origins, courses,
      anastomoses, and target tissues of the vessels that arise from the V2 segment.
      This new classification allows for better understanding of the vasculature of the
      C3-6 region.

PMID- 15478369
TI  - An anatomical study of the C-2 pedicle.
AB  - OBJECT: The C-2 pedicle plays an important role regarding screw purchase for
      spinal fixation. The aim of this study was to measure the C-2 pedicle-related
      linear and angular parameters. METHODS: Seven parameters in 160 C-2 pedicles (80
      dry vertebrae) were measured using a Vernier caliper (accurate to 0.1 mm) and
      goniometer. The Student t-test was used to determine statistical significance.
      The authors found that the C-2 isthmus (pars interarticularis) and the C-2
      pedicle are distinct structures. The C-2 isthmus covers the pedicle. The isthmus
      is present between the superior and inferior articular processes, and the pedicle
      is the structure beneath the C-2 isthmus. It connects the lateral mass-inferior
      articular process to the body of the axis. The heights of the right and the left
      C-2 pediculoisthmic components (PICs) were 10.3 +/- 1.6 and 9.9 +/- 1.5 mm,
      respectively. The posterior part of the superior aspect of the PIC was wider than
      the anterior portion. The widths of the posterosuperior aspect of the PIC were
      11.1 +/- 2 and 11 +/- 1.7 mm on the right and left sides, whereas the widths of
      the anterosuperior aspect of the PIC were 7.9 +/- 1.7 and 8.5 +/- 1.6 mm,
      respectively. The inferior widths of this component were 6.0 +/- 1.5 and 5.5 +/-
      1.3 mm on the right and left side, respectively. The lengths of the component
      were 28.8 +/- 2.9 mm on the right and 28.8 +/- 3.4 mm on the left side. The PIC
      exhibits a lateral-to-medial and an inferior-to-superior angle. Its axial angles
      were 28.4 +/- 2.5 and 28.6 +/- 2.2 degrees on the right and left sides,
      respectively; its sagittal angles were 18.8 +/- 2.1 and 18.8 +/- 1.7 degrees,
      respectively. CONCLUSIONS: The C-2 pedicle can be seen in the inferior aspect of
      the vertebra, and it connects posterior vertebral elements (that is, the lateral
      mass and inferior articular process) to the axial body. The isthmus drapes the
      pedicle. The authors suggest that this be termed "the pediculoisthmic component."

PMID- 15478370
TI  - Inhibition of the nuclear factor-kappaB activation with pyrrolidine
      dithiocarbamate attenuating inflammation and oxidative stress after experimental
      spinal cord trauma in rats.
AB  - OBJECT: The nuclear factor-kappaB (NF-kappaB) is a transcription factor that
      plays a pivotal role in the induction of genes involved in physiological
      processes and in the response to inflammation. The authors of recent studies have
      demonstrated that NF-kappaB and oxidative stress contribute to secondary injury
      after impact-induced spinal cord injury (SCI) in the rat. Dithiocarbamates are
      antioxidants that are potent inhibitors of NF-kappaB. The authors postulated that
      pyrrolidine dithiocarbamate (PDTC) would attenuate NF-kappaB-related inflammatory
      and oxidative events that occur after SCI. METHODS: Spinal cord injury was
      induced by the application of vascular clips (force of 50 g) to the dura mater
      after a four-level T5-8 laminectomy. The authors investigated the effects of PDTC
      (30 mg/kg administered 30 minutes before SCI and 6 hours after SCI) on the
      development of the inflammatory response associated with SCI in rats. Levels of
      myeloperoxidase activity were measured as an indicator of polymorphonuclear
      infiltration; malondialdehyde levels in the spinal cord tissue were determined as
      an indicator of lipid peroxidation. The following studies were performed:
      immunohistochemical analysis to assess levels of inducible nitric oxide synthase
      (iNOS), nitrotyrosine formation, poly([adenosine diphosphate]-ribose) polymerase
      (PARP) activity; Western blot analysis to determine cytoplasmic levels of
      inhibitory-kappaB-alpha (IkappaB-alpha); and electrophoretic mobility-shift assay
      to measure the level of DNA/NF-kappaB binding. The PDTC treatment exerted potent
      antiinflammatory effects with significant reduction of polymorphonuclear cell
      infiltration, lipid peroxidation, and iNOS activity. Furthermore, administration
      of PDTC reduced immunohistochemical evidence of formation of nitrotyrosine and
      PARP activation in the spinal cord section obtained in the SCI-treated rats.
      Additionally, PDTC treatment significantly prevented the activation of NF-kappaB
      (electrophoretic mobility-shift assay and immunoblot analysis). CONCLUSIONS:
      Overall, the results clearly demonstrate that PDTC-related prevention of the
      activation of NF-kappaB reduces the development of some secondary injury events
      after SCI. Therefore, inhibition of NF-kappaB may represent a novel approach in
      the treatment of SCIs.

PMID- 15478371
TI  - Mechanically engineered hydrogel scaffolds for axonal growth and angiogenesis
      after transplantation in spinal cord injury.
AB  - OBJECT: Spinal cord injury (SCI) is a complex pathological entity, the treatment
      of which requires a multipronged approach. One way to integrate different
      therapeutic strategies for SCI is to develop implantable scaffolds that can
      deliver therapies in a synergistic manner. Many investigators have developed
      implantable "bridges," but an important property of such scaffolds--that is,
      mechanical compatibility with host tissues--has been neglected. In this study,
      the authors evaluated the results of implanting a mechanically matched hydrogel
      based scaffold to treat SCI. METHODS: A nonbiodegradable hydrogel, poly(2
      hydroxyethylmethacrylate) (PHEMA), was engineered using thermally initiated free
      radical solution polymerization. Two groups of 12 adult Sprague-Dawley rats
      underwent partial cervical hemisection injury followed by implantation of either
      PHEMA or PHEMA soaked in 1 microg of brain-derived neurotrophic factor (BDNF).
      Four rats from each group were killed 1, 2, or 4 weeks after induction of the
      injury. Immunofluorescence staining was performed to determine the presence of
      scarring, cellular inflammatory responses, gliosis, angiogenesis, and axonal
      growth in and around the implanted scaffolds. CONCLUSIONS: The implanted PHEMA
      with 85% water content had a compressive modulus of 3 to 4 kPa, which matched the
      spinal cord. Implanted PHEMA elicited modest cellular inflammatory responses that
      disappeared by 4 weeks and minimal scarring was noted around the matrix.
      Considerable angiogenesis was observed in PHEMA, and PHEMA soaked in BDNF
      promoted axonal penetration into the gel. The authors conclude that mechanically
      engineered PHEMA is well accepted by host tissues and might be used as a platform
      for sustained drug delivery to promote axonal growth and functional recovery
      after SCI.

PMID- 15478372
TI  - Minimally invasive delivery of stem cells for spinal cord injury: advantages of
      the lumbar puncture technique.
AB  - OBJECT: Stem cell therapy has been shown to have considerable therapeutic
      potential for spinal cord injuries (SCIs); however, most experiments in animals
      have been performed by injecting cells directly into the injured parenchyma. This
      invasive technique compromises the injured spinal cord, although it delivers
      cells into the hostile environment of the acutely injured cord. In this study,
      the authors tested the possibility of delivering stem cells to injured spinal
      cord by using three different minimally invasive techniques. METHODS: Bone marrow
      stromal cells (BMSCs) are clinically attractive because they have shown
      therapeutic potential in SCI and can be obtained in patients at the bedside,
      raising the possibility of autologous transplantation. In this study
      transgenically labeled cells were used for transplantation, facilitating
      posttransplantation tracking. Inbred Fisher-344 rats received partial cervical
      hemisection injury, and 2 x 10(6) BMSCs were intravenously, intraventricularly,
      or intrathecally transplanted 24 hours later via lumbar puncture (LP). The
      animals were killed 3, 10, or 14 days posttransplantation, and tissue samples
      were submitted to histochemical and immunofluorescence analyses. For additional
      comparison and validation, lineage restricted neural precursor (LRNP) cells
      obtained from E13.5 rat embryos were transplanted via LP, and these findings were
      also analyzed. CONCLUSIONS: Both BMSCs and LRNP cells home toward injured spinal
      cord tissues. The use of LP and intraventricular routes allows more efficient
      delivery of cells to the injured cord compared with the intravenous route. Stem
      cells delivered via LP for treatment of SCI may potentially be applicable in
      humans after optimal protocols and safety profiles are established in further
      studies.

PMID- 15478373
TI  - Anomalous vertebral artery at the craniovertebral junction in a patient with Down
      syndrome. Case report.
AB  - The authors report a case of a patient with Down syndrome in whom the abnormal
      course of the right vertebral artery (VA) at the craniovertebral junction (CVJ)
      was accurately demonstrated on three-dimensional (3D) computerized tomography
      (CT) angiography. The patient was a 5-year-old boy, who developed severe
      myelopathy. Bone abnormalities were also present at the CVJ, including
      atlantoaxial and occipitoatlantal instabilities, a hypoplastic odontoid process,
      and ossiculum terminale. Three-dimensional CT angiography revealed that the right
      VA was duplicated after emerging from the C-2 transverse foramen. One half of the
      duplication, an artery that was as large as the left VA, turned posteromedially
      and entered the spinal canal between C-1 and C-2. The other half, a very small
      artery, ran as usual and passed through the C-1 transverse foramen. The authors
      performed an occipitocervical posterior fusion and a C-1 laminectomy.
      Intraoperatively the course of the anomalous VA was identified on Doppler
      ultrasonography, and the surgical approach and bone excision were undertaken
      carefully to avoid VA injury. Postoperatively, resolution of myelopathy was
      marked. In the surgical treatment of patients with Down syndrome, surgeons should
      consider the possibility that a VA anomaly is present at the CVJ. With
      preoperative 3D CT angiography, the anomalous VA can be identified precisely and
      the possible risk of intraoperative VA injury predetermined.

PMID- 15478374
TI  - Trevor disease of the spine. Case report.
AB  - The authors report the case of a 15-year-old boy who presented with left shoulder
      pain and paresthesia of the left hand. Imaging studies revealed an osseous lesion
      compressing the C-8 nerve root. The patient underwent tumor resection followed by
      instrumentation-augmented fusion. Histological findings were consistent with
      osteochondroma. The tumor most likely originated from the articular cartilage
      between the first rib and T-1 or between C-7 and T-1. The correct diagnosis,
      therefore, was dysplasia epiphysialis hemimelica (DEH), also known as Trevor
      disease. To the authors' knowledge, this is the first report of DEH involving the
      spine.

PMID- 15478375
TI  - Atlantoaxial instability.

PMID- 15478377
TI  - The importance of allergy/immunology rotations as an educational and promotional
      tool for our subspecialty.

PMID- 15478379
TI  - A 17-month-old boy with periorbital swelling.

PMID- 15478378
TI  - Rationale for new treatments aimed at IgE immunomodulation.
AB  - OBJECTIVE: To review potential or current therapies that decrease IgE synthesis
      or effects. DATA SOURCES: Relevant literature in peer-reviewed journals and
      abstracts from national meetings. STUDY SELECTION: Key articles were selected by
      the authors. RESULTS: Modulation of IgE-mediated diseases can occur at several
      levels. Transcription factors may be altered to differentiate lymphocytes into a
      TH1 phenotype, thus decreasing TH2-driven IgE production. This may be
      accomplished by inhibiting GATA-3 with peroxisome proliferator-activated receptor
      agonists or promoting T-bet expression with CpG motifs. Inhibiting IgE-promoting
      cytokines may be accomplished by blocking the effects or synthesis of interleukin
      4 (IL-4) or IL-13 by suplatast tosilate. Cytokine therapy with anti-IL-4 or anti
      IL-13 has the potential to directly influence IgE-mediated diseases, but
      strategies aimed at IL-4 alone have been disappointing. Clinical trials with
      interferon-gamma or IL-12, 2 cytokines important in promoting TH1 and inhibiting
      TH2 responses, have been fraught with adverse effects that make their use
      limited. The use of plasmids encoding interferon-gamma or IL-12 has shown promise
      in animal models. Inhibition of IgE synthesis has been demonstrated with anti
      CD23 antibodies. Early human studies have been very encouraging, and larger
      studies are under way. The only IgE immunomodulator currently available for use
      is omalizumab. Omalizumab is effective for allergic asthma in children and
      adults. CONCLUSIONS: Newer therapies hold great promise for the future treatment
      of allergic respiratory diseases, but clinical trials are necessary to accurately
      evaluate risk-benefit ratios of IgE immunomodulators.

PMID- 15478380
TI  - Physician attitudes, opinions, and referral patterns: comparisons of those who
      have and have not taken an allergy/immunology rotation.
AB  - BACKGROUND: Interest in the field of allergy/immunology (A/I) is increasing, yet
      resident training programs are under pressure to shorten elective rotations such
      as A/I. It is unclear if there are differences between those who have and have
      not taken an A/I rotation. OBJECTIVE: To evaluate differences in the attitudes,
      opinions, and referral patterns between physicians who have and have not taken an
      A/I rotation. METHODS: An anonymous questionnaire was sent to 375 primary care
      physicians at one academic medical center. Subjects were separated into 5 cohorts
      based on specialty and level of training (internal medicine faculty, internal
      medicine resident, pediatric faculty, pediatric resident, and internal medicine
      pediatric resident). RESULTS: Of the participants, 227 (61.0%) completed the
      survey. Compared with those who had not taken an A/I rotation, those who had
      taken an A/I rotation were more likely to feel they knew the types of cases seen
      by an allergist (75.9% vs 33.3%), to feel they knew an adequate amount about A/I
      (59.3% vs 19.5%), to feel they were exposed to an adequate amount of A/I during
      residency (64.8% vs 9.8%), to view immunotherapy as effective (70.0% vs 52.3%),
      and to have referred a patient to an allergist (77.8% vs 46.0%). CONCLUSIONS:
      There are significant differences in the attitudes, opinions, and referral
      patterns between physicians who have and have not taken an A/I rotation. Allergic
      diseases are increasing, yet residency training programs are under pressure to
      shorten rotations such as A/I to accommodate federally mandated work hour
      restrictions. The potential for inadequate care of allergic diseases may be an
      important issue if these trends continue.

PMID- 15478382
TI  - Changing physician prescribing patterns through problem-based learning: an
      interactive, teleconference case-based education program and review of problem
      based learning.
AB  - BACKGROUND: Although asthma guidelines have recommended the use of anti
      inflammatory controller medications since 1991, studies have consistently shown
      widespread failure to follow the guidelines. Major barriers include lack of
      knowledge and the inability to operationalize knowledge. Improved continuing
      medical education methods should result in more effective learning by physicians
      and other health care professionals, leading to better adherence to guidelines,
      resulting in better outcomes. OBJECTIVE: To evaluate the effectiveness of an
      interactive, case-based, educational intervention, also known as problem-based
      learning, using a series of interactive, case-based teleconferences. METHODS: A
      series of interactive, case-based teleconferences was completed with 20 primary
      care physicians. Each case involved a child aged 16 months to 12 years with
      asthma. A 12-month analysis of physician prescribing patterns was conducted.
      RESULTS: Program acceptance by the 20 physicians was uniformly positive.
      Significant improvement was noted, with an overall increase in controller use.
      Review of prescription data showed an increase in inhaled corticosteroid use from
      an average of 2.54 to 7.76 refills per month for the 6 months after the
      intervention (P < .001). CONCLUSIONS: After participating in a unique educational
      intervention-problem-based learning using interactive, case-based teleconferences
      the prescribing patterns of physicians were altered significantly toward better
      adherence to asthma guidelines, as demonstrated by an increased use of anti
      inflammatory controller medications (inhaled corticosteroids and leukotriene
      antagonists).

PMID- 15478381
TI  - Effectiveness of montelukast in the treatment of cough variant asthma.
AB  - BACKGROUND: Antileukotriene agents have been shown to be beneficial in chronic
      asthma. Although patients with cough variant asthma have cough with minimal
      wheezing and dyspnea, airway hyperresponsiveness from chronic inflammation is
      believed to be the underlying mechanism. OBJECTIVE: To evaluate the effectiveness
      of montelukast, a leukotriene receptor antagonist, in the treatment of cough
      variant asthma. METHODS: Fourteen patients with cough variant asthma participated
      in a randomized, double-blind, placebo-controlled trial with a 7- to 10-day
      baseline period and a 4-week treatment period with montelukast, 10 mg, or placebo
      daily. Inclusion criteria were (1) chronic cough with a duration of at least 4
      weeks with minimal or no wheezing or dyspnea and (2) forced expiratory volume in
      1 second of 50% to 85% of predicted and reversibility of 12% with use of an
      inhaled beta-agonist or forced expiratory volume in 1 second greater than 85% and
      positive methacholine challenge results. Patients fulfilled the minimum criteria
      for cough frequency and symptom scores for randomization. RESULTS: Eight patients
      received montelukast and 6 received placebo. The primary efficacy variable, mean
      percentage change from baseline in cough frequency, was significantly improved by
      the second week, and by the fourth week the mean percentage change from baseline
      was 75.7% for the treatment group and 20.7% for the placebo group. CONCLUSIONS:
      The leukotriene receptor antagonist montelukast seems to be effective in the
      treatment of cough variant asthma. Larger studies are recommended to confirm this
      effect.

PMID- 15478383
TI  - Effects of omalizumab, a humanized monoclonal anti-IgE antibody, on nasal
      reactivity to allergen and local IgE synthesis.
AB  - BACKGROUND: Treatment with omalizumab has been shown to reduce serum free IgE
      concentrations and to have beneficial effects on allergic airway disease.
      However, its effect on IgE synthesis is unknown. OBJECTIVE: To determine whether
      omalizumab therapy affects nasal reactivity to allergen and local IgE production.
      METHODS: Nineteen patients with perennial allergic rhinitis were treated with
      intravenous omalizumab every 2 weeks for 26 weeks in an open-label study. Serum
      free and total IgE concentrations were measured at baseline and every 2 weeks
      throughout the study. Nasal challenge to dust mite allergen was performed at
      baseline and after 12 and 24 weeks of treatment. Nasal lavage fluid obtained
      before and after each nasal challenge was evaluated for mite-specific antibodies,
      plaque-forming cells, and productive epsilon messenger RNA (mRNA). RESULTS:
      During treatment, serum free IgE concentrations were decreased by 97% to 99%, and
      the nasal response to allergen challenge was significantly reduced on days 80 and
      164. The postchallenge increase in nasal lavage mite specific IgE was
      significantly reduced by treatment with omalizumab on day 168. IgE plaque-forming
      cells and productive epsilon mRNA were not significantly affected by omalizumab
      treatment. CONCLUSIONS: Omalizumab treatment markedly reduced serum free IgE and
      the clinical response to nasal allergen challenge. However, the absence of an
      effect on IgE-secreting B cells and epsilon mRNA in nasal lavage fluid suggests
      that omalizumab treatment for 6 months does not significantly modulate synthesis
      of nasal IgE.

PMID- 15478384
TI  - Comparison of efficiency and preference of metal and plastic spacers in preschool
      children.
AB  - BACKGROUND: The metal NebuChamber valved holding chamber (VHC) has gained wide
      acceptance among children with asthma. Due to its nonelectrostatic properties and
      larger volume, the 250-mL, metal NebuChamber delivers a greater mass of aerosol
      to a filter at the mouth compared with the commonly used 150-mL polypropylene
      AeroChamber VHC. Such in vitro results have been used to suggest that this may
      provide increased efficacy with the NebuChamber. No comparative efficacy data
      exist for preschool children with asthma. OBJECTIVE: To compare efficiency and
      preference of metal and plastic spacers in preschool children. METHODS: Children
      with mild-to-moderate persistent asthma received 200 microg of budesonide twice
      daily by NebuChamber or AeroChamber, both with the mask provided in a randomized,
      2-month, crossover trial. Symptom diary cards, beta-agonist use, and preference
      by children and parents were compared. RESULTS: Thirty children (mean +/- SD age,
      4.3 +/- 0.3 years) completed the study. There was no difference between the
      AeroChamber and NebuChamber in clinical efficacy outcomes. There was no
      difference between the AeroChamber and NebuChamber in parents' view of ease of
      use, design, acceptability by the children, and overall satisfaction.
      CONCLUSIONS: Despite a greater total dose delivered to the mouth, the NebuChamber
      appears no more effective than the AeroChamber and it is not preferred by
      patients or parents. More parents chose to continue to use the NebuChamber after
      the study.

PMID- 15478386
TI  - Comparison of objective and subjective measurements of cough frequency in
      patients with seasonal allergic rhinitis.
AB  - BACKGROUND: Cough is a frequent complaint of patients with a variety of
      respiratory disorders, including seasonal allergic rhinitis (SAR), and it is
      often evaluated subjectively to determine disease status and response to
      treatment. However, it is not known whether subjective reports of cough from
      patients with SAR are accurate. OBJECTIVE: To compare a novel objective
      measurement with subjective reports of cough frequency in a subset of 28 patients
      (aged > or = 12 years) with active SAR who were enrolled in a large, multicenter
      trial examining the efficacy of an active treatment for SAR. METHODS: In this
      supplemental pilot study, subjective data were collected on a diary card and
      objective data were collected using home-based telemetry. Three 24-hour recording
      sessions were conducted with each patient: 2 consecutive baseline sessions (day 1
      and day 2) and 1 session after randomization to placebo or active cough treatment
      (day 3). RESULTS: Strong correlations existed between cough frequency data for
      days 1 and 2 (Spearman correlation coefficient = 0.91; P < .001) and between
      subjective and objective data for days 1, 2, and 3 (daytime greater than
      nighttime) (Spearman correlation coefficient = 0.51; P < .001). CONCLUSION: These
      results have implications for the design and interpretation of results from
      clinical trials that evaluate cough frequency as a treatment outcome.

PMID- 15478387
TI  - Association between asthma control in children and loss of workdays by
      caregivers.
AB  - BACKGROUND: Although the economic burden of pediatric asthma is a significant
      public health issue, the loss of workdays by caregivers because of their
      children's asthma remains scarcely investigated. OBJECTIVES: To evaluate asthma
      related loss of workdays incurred by caregivers of asthmatic children and its
      association with the level of asthma control. METHODS: A retrospective
      observational study was conducted based on a French computerized general
      practitioners' database and a survey questionnaire. Children aged 6 to 16 years
      with persistent asthma (Global Initiative for Asthma grade > or = 2) were
      included in the study. Level of children's asthma control was evaluated from
      recent asthma symptoms. Caregivers reported the number of workdays lost because
      of their child's asthma during the 12-month study. RESULTS: Nearly 30% of
      caregivers lost workdays during the study because of their children's asthma.
      More than 13% of caregivers lost more than 5 days. Caregiver absenteeism
      significantly correlated with all components of asthma control (use of relievers,
      nocturnal symptoms, impairment of activities, and asthma crises). A significant 8
      fold risk of losing more than 5 workdays by caregivers was observed when the
      child's asthma was poorly controlled (odds ratio, 8.6; 95% confidence interval,
      2.4-30.5); caregivers' absenteeism also increased significantly with the number
      of episodes of oral corticosteroid use during the study. CONCLUSIONS: Caregivers'
      loss of workdays owing to their children's asthma is substantial and is highly
      correlated with the level of asthma control. These findings highlight the
      necessity of educational programs for children with poor asthma control and their
      caregivers to prevent severe asthma attacks that lead to caregiver absenteeism.

PMID- 15478385
TI  - Effects of high-dose inhaled fluticasone propionate on the hypothalamic-pituitary
      adrenal axis in asthmatic patients with severely impaired lung function.
AB  - BACKGROUND: The effects of high-dose fluticasone propionate therapy on dynamic
      cortisol stimulation in severe asthma are unknown. OBJECTIVE: To evaluate the
      human corticotropin-releasing factor (hCRF)-stimulated plasma cortisol response
      to fluticasone propionate therapy in severe asthmatic patients with impaired
      airway caliber (forced expiratory volume in 1 second [FEV1] < 60% of predicted)
      and in control subjects. METHODS: Ten severe asthmatic patients (mean FEV1, 47%
      of predicted) and 10 controls (mean FEV1, 104% of predicted) received fluticasone
      propionate, 2,000 microg/d, via a 750-mL primed spacer for 2 weeks. Plasma
      cortisol levels before and after hCRF stimulation and overnight 10-hour urinary
      cortisol excretion corrected for creatinine concentration (OUCC) were measured at
      baseline after washout and 12 hours after the last dose of fluticasone
      propionate. RESULTS: Baseline values before fluticasone propionate use were not
      significantly different in asthmatic patients vs controls for plasma cortisol
      before and after hCRF stimulation and OUCC. Comparing values at baseline vs after
      fluticasone propionate use, there was no significant suppression of plasma
      cortisol levels before (378.2 vs 357.4 nmol/L) or after (510.5 vs 507.9 nmol/L)
      hCRF stimulation or OUCC (8.2 vs 7.5 nmoL/mmoL) in asthmatic patients. In
      controls, all outcomes were significantly suppressed comparing values before vs
      after fluticasone propionate therapy: plasma cortisol levels before (423.5 vs
      200.2 nmol/L; P = .002) and after (503.5 vs 291.1 nmol/L; P = .001) hCRF
      stimulation and OUCC (6.5 vs 2.4 nmol/mmol; P = .002). CONCLUSION: Patients with
      severe persistent asthma and impaired airway caliber seem to be protected from
      developing systemic adverse effects with high-dose fluticasone propionate
      therapy, as evaluated by basal and dynamic measures of hypothalamic-pituitary
      adrenal axis activity.

PMID- 15478388
TI  - Effect of influenza virus vaccine on the expression of human immunodeficiency
      virus co-receptor CCR5.
AB  - BACKGROUND: Administration of influenza vaccine to human immunodeficiency virus
      (HIV)-infected children can lead to increased viral load. CCR5 and CXCR4 are
      known to play an important role in HIV cell entry and viral replication.
      OBJECTIVE: To determine the effects of influenza vaccine on chemokine receptors
      and on viral load in HIV-infected children. METHODS: Eight HIV-infected children
      receiving stable therapy and 11 healthy adults were enrolled. Chemokine
      expression and immune activation were determined before and 48 hours after
      influenza vaccination. CCR5 and beta-chemokine gene expression were analyzed
      using real-time polymerase chain reaction. Viral load was measured at baseline,
      48 hours, and 6 to 12 weeks. RESULTS: Forty-eight hours after influenza
      vaccination, mean CCR5 expression was significantly decreased on the CD3 (21.1%
      vs 11.3% in HIV-infected children; P = .02; and 18.3% vs 10.7% in controls; P =
      .008) and CD4 (13.0% vs 3.6% in the HIV group; P = .04; and 13.6% vs 6.5% in
      controls; P = .02) lymphocytes. This was observed in conjunction with an increase
      in HLA-DR expression on T lymphocytes in HIV-infected children (P = .046). No
      significant changes were observed in HIV viral load, CD3 and CD8 lymphocyte
      counts, expression of interleukin 2 receptor and CXCR4, or gene expression of
      CCR5 and beta-chemokines 48 hours after vaccination. CONCLUSIONS: Influenza virus
      vaccine markedly decreased chemokine receptor CCR5 expression on CD4 T
      lymphocytes. However, this immunomodulatory effect does not seem to affect
      overall viral replication in HIV-infected children who received highly active
      antiretroviral therapy.

PMID- 15478389
TI  - Serum leptin levels in asthmatic children treated with an inhaled corticosteroid.
AB  - BACKGROUND: Recent observations suggest the presence of an interaction between
      leptin and the inflammatory system; however, there is no adequate knowledge about
      the role of leptin in atopic states such as asthma. OBJECTIVES: To evaluate the
      potential role of leptin in relation to bronchial asthma and inhaled
      corticosteroid therapy. METHODS: Twenty-three children with mild-to-moderate,
      newly diagnosed asthma enrolled in this 2-period trial. The control group
      consisted of 20 age- and sex-matched children. Serum leptin levels were measured
      in patients at initiation and after 4 weeks of budesonide treatment and were
      compared with control group measurements. RESULTS: Asthmatic children had higher
      mean +/- SD serum leptin levels at admission (19.3 +/- 5.1 ng/mL) than after
      budesonide treatment (10.6 +/- 1.6 ng/mL) and vs control group measurements (9.8
      +/- 1.6 ng/mL) (P < .001). There was a significant correlation between serum
      leptin levels before and after budesonide treatment (r = 0.68; P = .007). Mean +/
      SD body mass indices in patients and controls were 16.7 +/- 2.1 and 16.9 +/- 2.6
      kg/m2, respectively. Serum leptin levels did not correlate with body mass indices
      before budesonide treatment in the study group (r = -0.13; P = .65) but
      correlated well after budesonide treatment (r = 0.58; P = .009) and in the
      control group (r = 0.65; P = .008). CONCLUSIONS: The role of leptin elevation in
      children with asthma might be a regulatory mechanism rather than being etiologic,
      but a question may be raised whether it is possible that leptin may contribute to
      poor patient outcomes. Further research, both basic and clinical, is essential to
      explain the exact mechanism.

PMID- 15478390
TI  - Immunoblot and radioallergosorbent test inhibition studies of allergenic cross
      reactivity of the predatory mite Amblyseius cucumeris with the house dust mite
      Dermatophagoides pteronyssinus.
AB  - BACKGROUND: In 1999, an extensive study among bell pepper growers showed that a
      predatory mite, Amblyseius cucumeris, is a potentially relevant source of
      occupational allergens because 23% of the population had positive skin prick test
      reactions. OBJECTIVE: To investigate whether cross-reactivity between A.
      cucumeris and Dermatophagoides pteronyssinus is responsible for the
      cosensitization to both mite species found in 58.7% of A. cucumeris-sensitized
      greenhouse workers. METHODS: Fifteen serum samples from greenhouse workers with
      work-related inhalant allergy and a positive radioallergosorbent test (RAST)
      reaction to A. cucumeris or D. pteronyssinus were selected for immunoblot
      analysis using extracts of both mites. A subselection (n = 5) was used for RAST
      and immunoblot inhibition to investigate potential cross-reactivity. RESULTS: On
      immunoblot, 2 distinct patterns were observed: one pattern showed common protein
      bands in A. cucumeris and D. pteronyssinus blots suggestive of cross-reactivity
      between A. cucumeris and D. pteronyssinus and the other pattern showed no shared
      protein bands. Dermatophagoides pteronyssinus RAST inhibition with A. cucumeris
      extract was low in 4 serum samples (<25% inhibition) and nearly absent in 1 serum
      sample; A. cucumeris RAST inhibition with D. pteronyssinus extract was high in 1
      serum sample (75% inhibition), low in 2 serum samples (35% and <15% inhibition),
      and absent in 2 serum samples. These results were confirmed by immunoblot
      inhibition experiments. CONCLUSIONS: Amblyseius cucumeris, a new occupational
      allergen, has species-specific antigens and common antigens that are cross
      reactive with the house dust mite D. pteronyssinus.

PMID- 15478391
TI  - Lysozyme levels in the nasal secretions of patients with perennial allergic
      rhinitis and recurrent sinusitis.
AB  - BACKGROUND: The association of perennial allergic rhinitis (PAR) with recurrent
      sinusitis (RS) is well recognized. Anatomic abnormalities at the osteomeatal
      complex or ciliary dysfunction may play a significant role in some patients.
      However, for most patients with allergy, the determinants of RS are unknown.
      OBJECTIVE: To determine whether altered concentrations of antimicrobial peptides
      and proteins, such as lysozyme, lactoferrin, human beta-defensin-2 (HBD-2), and
      human neutrophil peptides 1 to 3 (HNP-1 to 3), contribute to the development of
      RS in patients with PAR. METHODS: Nasal secretions were collected by vacuum
      aspiration from 15 individuals with PAR+RS, 16 with PAR alone, and 16 controls.
      Lysozyme and lactoferrin levels were determined in nasal secretions by using
      quantitative enzyme-linked immunosorbent assay, and HBD-2 and HNP-1 to 3 levels
      were determined in nasal secretions by using semiquantitative Western blot
      analysis. Eosinophil-derived neurotoxin (EDN) levels were measured by using
      enzyme-linked immunosorbent assay as a marker of nasal eosinophilia in all 3
      groups. RESULTS: Levels of EDN were elevated significantly in patients with
      PAR+RS compared with controls. Lysozyme levels were decreased significantly in
      patients with PAR+RS compared with PAR alone or controls. Mean lysozyme levels
      were significantly lower in patients with EDN levels greater than 1,000 ng/mL vs
      those with levels of 1,000 ng/mL or less in the PAR+RS group. There were no
      statistically significant differences in lactoferrin, HBD-2, and HNP-1 to 3
      levels among the 3 groups. CONCLUSIONS: The presence of eosinophils and their
      products and reduced lysozyme concentrations may be critical factors that
      predispose the airways of patients with PAR to RS.

PMID- 15478392
TI  - Increased levels of IgG to cytokeratin 19 in sera of patients with toluene
      diisocyanate-induced asthma.
AB  - BACKGROUND: Inhaled isocyanate binds with cytokeratin (CK) of the epithelial
      cells, which could induce immune responses. OBJECTIVE: To elucidate the possible
      existence of an isocyanate-induced, asthma-associated autoantigen from the
      bronchial epithelial cells, which may be associated with toluene diisocyanate
      (TDI)-induced asthma development. METHODS: We cultured bronchial epithelial cells
      with incubation of TDI-human serum albumin (HSA) conjugate. Gene expression
      profiles of cultured epithelial cells were analyzed using a microarray technique.
      CK19 protein expression within the epithelial cells was confirmed by IgG
      immunoblot using monoclonal antibody to CK19. Serum IgG to CK19 and specific IgG
      and IgE antibodies to TDI-HSA conjugate were detected by enzyme-linked
      immunosorbent assay in 68 TDI asthma patients (group 1) and compared with 40
      allergic asthma patients (group 2) and 80 unexposed healthy controls (group 3).
      RESULTS: After TDI exposure, increased expression of CK19 and CK14 genes from the
      culture bronchial epithelial cells was noted using microarray analysis. IgG
      immunoblot analysis confirmed increased expression of CK19 after the TDI
      exposure. The levels of serum IgG to CK19 were significantly higher in the TDI
      asthma group than in groups 2 and 3 (P=.008). The prevalence of IgG to CK19 was
      significantly higher in group 1 (38.2%) than group 2 (22.5%) or group 3 (1.3%)
      (P=.008). Significant associations were noted between IgG to CK19 and specific
      IgG to TDI-HSA conjugate and transglutaminase (P=.02) but not with specific IgE
      to TDI-HSA conjugate. CONCLUSION: We suggest that TDI exposure can augment CK19
      expression from the bronchial epithelial cell, which may involve immune responses
      as an autoantigen to induce airway inflammation in TDI-induced asthma.

PMID- 15478393
TI  - Eucalyptus as a specific irritant causing vocal cord dysfunction.
AB  - BACKGROUND: Vocal cord dysfunction (VCD) is a well-recognized clinical entity
      that frequently mimics asthma and is characterized by inappropriate adduction of
      the vocal cords during inspiration. The pathogenesis of VCD has not yet been
      defined. The only previous report suggested that respiratory irritants may
      trigger paradoxical motion of the vocal cords. OBJECTIVE: To report the case of a
      46-year-old woman with VCD precipitated by eucalyptus exposure. METHODS: A masked
      flexible fiberoptic nasolaryngoscopy was performed to confirm whether VCD
      occurred with eucalyptus and not with other known respiratory irritants. The
      patient underwent inhalation challenges consisting of water, ammonia, pine oil,
      and a combination of eucalyptus (dried leaves) and ammonia. Two independent
      observers before patient challenge could not identify eucalyptus. RESULTS: Vocal
      cord dysfunction occurred within minutes of exposure to eucalyptus. This is the
      first report to prospectively document that a specific irritant, eucalyptus, can
      precipitate VCD. Negative skin prick test results, total IgE level, and negative
      IgE eucalyptus-specific antibodies support a nonimmunologic mechanism.
      CONCLUSIONS: A new pathogenic mechanism for this clinical entity is supported by
      our observations. Furthermore, a nonimmunologic mechanism in which respiratory
      irritants may induce VCD is suspected. Future studies to elucidate this mechanism
      need to be performed in individuals with irritant-specific VCD.

PMID- 15478394
TI  - Heparin hypersensitivity: a case of mistaken identity.

PMID- 15478395
TI  - Disease management of atopic dermatitis: an updated practice parameter. Joint
      Task Force on Practice Parameters.

PMID- 15478399
TI  - On the dichotomy in auditory perception between temporal envelope and fine
      structure cues.

PMID- 15478401
TI  - A fast Fourier transform on multipoles (FFTM) algorithm for solving Helmholtz
      equation in acoustics analysis.
AB  - This article presents a fast algorithm for the efficient solution of the
      Helmholtz equation. The method is based on the translation theory of the
      multipole expansions. Here, the speedup comes from the convolution nature of the
      translation operators, which can be evaluated rapidly using fast Fourier
      transform algorithms. Also, the computations of the translation operators are
      accelerated by using the recursive formulas developed recently by Gumerov and
      Duraiswami [SIAM J. Sci. Comput. 25, 1344-1381(2003)]. It is demonstrated that
      the algorithm can produce good accuracy with a relatively low order of expansion.
      Efficiency analyses of the algorithm reveal that it has computational
      complexities of O(Na), where a ranges from 1.05 to 1.24. However, this method
      requires substantially more memory to store the translation operators as compared
      to the fast multipole method. Hence, despite its simplicity in implementation,
      this memory requirement issue may limit the application of this algorithm to
      solving very large-scale problems.

PMID- 15478411
TI  - Resonance frequency of microbubbles: effect of viscosity.
AB  - The transmitted frequency at which a gas bubble of millimeter or submillimeter
      size oscillates resonantly in a low-viscosity liquid is approximately equal to
      the undamped natural frequency (referred to as the Minnaert frequency if surface
      tension effects are disregarded). Based on a theoretical analysis of bubble
      oscillation, this paper shows that such an approximation cannot be validated for
      microbubbles used in contrast-enhanced ultrasound imaging. The contrast-agent
      microbubbles represent either encapsulated bubbles of size less than 10 microm or
      free (nonencapsulated) bubbles of submicron size. The resonance frequency of the
      microbubbles deviates significantly from the undamped natural frequency over the
      whole range of microbubble sizes due to the increased viscous damping
      coefficient. The difference between these two frequencies is shown to have a
      tremendous impact on the resonant backscatter by the microbubbles. In particular,
      the first and second harmonics of the backscattered signal from the microbubbles
      are characterized by their own resonance frequencies, equal to neither the
      microbubble resonance frequency nor the undamped natural frequency.

PMID- 15478415
TI  - Focused array transducer for two-dimensional optoacoustic tomography.
AB  - Optoacoustic (OA) imaging utilizes short laser pulses to create acoustic sources
      in tissue and time resolved detection of generated pressure profiles for image
      reconstruction. The ultrasonic transients provide information on the distribution
      of optical absorption coefficient that can be useful for early cancer
      diagnostics. In this work a new design of wide-band array transducer is developed
      and tested. The array consists of 32 focused piezo-elements made of PVDF slabs
      imposed on a cylindrical surface. A single array element response to an OA signal
      coming from arbitrarily located point source is investigated theoretically and
      experimentally. The measured signals correspond well to numerically calculated
      ones. Focal zone maps of the elements with aperture angles 30 degrees and 60
      degrees are presented and discussed; the resolution in direction perpendicular to
      the imaging plane is determined. Point spread function of the whole array is
      calculated using experimentally obtained signals from the sources located at
      different distances from the array. Backprojection algorithm is employed for
      reconstruction of the optoacoustic images. It is shown that the spatial
      resolution of the images yielded by the proposed array increases significantly
      compared to previous transducer designs.

PMID- 15478423
TI  - Subjective response of people to simulated sonic booms in their homes.
AB  - In order to determine the effect of the number of sonic boom occurrences on
      annoyance, a computer-based system was developed for studying the subjective
      response of people to the occurrence of simulated sonic booms in their homes. The
      system provided a degree of control over the noise exposure not found in
      community surveys and a degree of situational realism not available in the
      laboratory. A system was deployed for eight weeks in each of 33 homes. Each day
      from 4 to 63 sonic booms were played as the test subject went about his or her
      normal activities. At the end of the day, the test subjects rated their annoyance
      to the sonic booms heard during the day. The sonic booms consisted of different
      combinations of waveforms, levels, and occurrence rates. The experiment confirmed
      that the increase in annoyance resulting from multiple occurrences can be modeled
      by the addition of the term "10 * log(number of occurrences)" to the sonic boom
      level. Of several noise metrics considered, perceived level was the best
      annoyance predictor. Comparisons of the subjective responses to the different
      sonic boom waveforms found no differences that were not accounted for by the
      noise metrics.

PMID- 15478426
TI  - Listening difficulty as a subjective measure for evaluation of speech
      transmission performance in public spaces.
AB  - Listening difficulty ratings, using words with high word familiarity, are
      proposed as a new subjective measure for the evaluation of speech transmission in
      public spaces to provide realistic and objective results. Two listening tests
      were performed to examine their validity, compared with intelligibility scores.
      The tests included a reverberant signal and noise as detrimental sounds. The
      subject was asked to repeat each word and simultaneously to rate the listening
      difficulty into one of four categories: (1) not difficult, (2) a little
      difficult, (3) fairly difficult, and (4) extremely difficult. After the tests,
      the four categories were reclassified into, not difficult [response (1)] and some
      level of difficulty, (the other 3 responses). Listening difficulty is defined as
      the percentage of the total number of responses indicating some level of
      difficulty [i.e. not (1)]. The results of two listening tests demonstrated that
      listening difficulty ratings can evaluate speech transmission performance more
      accurately and sensitively than intelligibility scores for sound fields with
      higher speech transmission performance.

PMID- 15478429
TI  - Modeling the growth rate of distortion product otoacoustic emissions by active
      nonlinear oscillators.
AB  - In this work, growth-rate curves of the 2 f1-f2 distortion product otoacoustic
      emission (DPOAE) are analyzed in a population of 30 noise exposed subjects,
      including both normal-hearing and hearing impaired subjects. A particular
      embedded limit-cycle oscillator equation is used to model the cochlear resonant
      response at the cochlear places of the primary and secondary tone frequencies (f2
      and 2 f1-f2). The parameters of the oscillator equation can be directly
      interpreted in terms of effectiveness of the cochlear feedback mechanisms
      associated with the active filter amplification. A two-sources paradigm is
      included in the model, in agreement with experimental evidence and with the
      assumptions of more detailed full cochlear models based on the transmission line
      formalism. According to this paradigm, DPOAEs are nonlinearly generated at the
      cochlear place that is resonant at frequency f2, and coherently reflected at the
      2 f1-f2 place. The analysis shows that the model, which had been previously used
      to describe the relaxation dynamics of transient evoked otoacoustic emissions
      (TEOAEs), also correctly predicts the observed growth rate of the DPOAE response
      as a function of the primary tones amplitude. A significant difference is
      observed between normal and impaired ears. The comparison between the growth rate
      curves at different frequencies provides information about the dependence of
      cochlear tuning on frequency.

PMID- 15478430
TI  - Frequency specificity of distortion-product otoacoustic emissions produced by
      high-level tones despite inefficient cochlear electromechanical feedback.
AB  - Distortion product otoacoustic emissions (DPOAEs) are thought to stem from the
      outer hair cells (OHCs) around the normally narrow place tuned to the primary
      tone stimuli. They are thus said to be frequency-specific: their local absence
      should accurately pinpoint local OHC damage. Yet the influence of impaired tuning
      on DPOAE frequency specificity is poorly documented. Mice with local damage to
      OHCs were examined. Their DPOAEs were frequency-specific in that audiometric
      notches were accurately tracked. The same cochleae were further impaired by
      ischemia or furosemide injection inducing strial dysfunction with flat loss of
      sensitivity and tuning, while the preexisting pattern of damaged OHCs remained
      unaltered. Despite the loss of cochlear activity, DPOAEs produced by high-level
      (> or =70 dB SPL) primaries remained large in about the same interval where they
      had been initially normal, i.e., that with nondamaged OHCs, albeit with a slight
      frequency shift, of -1.1 kHz on average. Thus, the ability of DPOAEs to map
      structurally intact OHCs cannot be a mere consequence of cochlear tuning as it
      largely persists in its absence. The key element for this correct mapping is
      likely part of intact OHC structures (e.g., stereocilia bundles) and must have
      some tuning of its own.

PMID- 15478431
TI  - Otoacoustic emissions without somatic motility: can stereocilia mechanics drive
      the mammalian cochlea?
AB  - Distortion product otoacoustic emissions (DPOAEs) evoked by low-level tones are a
      sensitive indicator of outer hair cell (OHC) function. High-level DPOAEs are less
      vulnerable to cochlear insult, and their dependence on the OHC function is more
      controversial. Here, the mechanism underlying high-level DPOAE generation is
      addressed using a mutant mouse line lacking prestin, the molecular motor driving
      OHC somatic motility, required for cochlear amplification. With prestin deletion,
      attenuated DPOAEs were measurable at high sound levels. DPOAE thresholds were
      shifted by approximately 50 dB, matching the loss of cochlear amplifier gain
      measured in compound action potentials. In contrast, at high sound levels,
      distortion products in the cochlear microphonic (CM) of mutants were not
      decreased re wildtypes (expressed re CM at the primaries). Distortion products in
      both CM and otoacoustic emissions disappeared rapidly after death. The results
      show that OHC somatic motility is not necessary for the production of DPOAEs at
      high SPLs. They also suggest that the small, physiologically vulnerable DPOAE
      that remains without prestin-based motility is due directly to the mechanical
      nonlinearity associated with stereociliary transduction, and that this
      stereocilia mechanical nonlinearity is robustly coupled to the motion of the
      cochlear partition to the extent that it can drive the middle ear.

PMID- 15478432
TI  - Auditory stream segregation in monkey auditory cortex: effects of frequency
      separation, presentation rate, and tone duration.
AB  - Auditory stream segregation refers to the organization of sequential sounds into
      "perceptual streams" reflecting individual environmental sound sources. In the
      present study, sequences of alternating high and low tones, "...ABAB...," similar
      to those used in psychoacoustic experiments on stream segregation, were presented
      to awake monkeys while neural activity was recorded in primary auditory cortex
      (A1). Tone frequency separation (AF), tone presentation rate (PR), and tone
      duration (TD) were systematically varied to examine whether neural responses
      correlate with effects of these variables on perceptual stream segregation. "A"
      tones were fixed at the best frequency of the recording site, while "B" tones
      were displaced in frequency from "A" tones by an amount = delta F. As PR
      increased, "B" tone responses decreased in amplitude to a greater extent than "A"
      tone responses, yielding neural response patterns dominated by "A" tone responses
      occurring at half the alternation rate. Increasing TD facilitated the
      differential attenuation of "B" tone responses. These findings parallel
      psychoacoustic data and suggest a physiological model of stream segregation
      whereby increasing delta F, PR, or TD enhances spatial differentiation of "A"
      tone and "B" tone responses along the tonotopic map in A1.

PMID- 15478433
TI  - Relative importance of temporal information in various frequency regions for
      consonant identification in quiet and in noise.
AB  - The relative importance of temporal information in broad spectral regions for
      consonant identification was assessed in normal-hearing listeners. For the
      purpose of forcing listeners to use primarily temporal-envelope cues, speech
      sounds were spectrally degraded using four-noise-band vocoder processing
      Frequency-weighting functions were determined using two methods. The first method
      consisted of measuring the intelligibility of speech with a hole in the spectrum
      either in quiet or in noise. The second method consisted of correlating
      performance with the randomly and independently varied signal-to-noise ratio
      within each band. Results demonstrated that all bands contributed equally to
      consonant identification when presented in quiet. In noise, however, both methods
      indicated that listeners consistently placed relatively more weight upon the
      highest frequency band. It is proposed that the explanation for the difference in
      results between quiet and noise relates to the shape of the modulation spectra in
      adjacent frequency bands. Overall, the results suggest that normal-hearing
      listeners use a common listening strategy in a given condition. However, this
      strategy may be influenced by the competing sounds, and thus may vary according
      to the context. Some implications of the results for cochlear implantees and
      hearing-impaired listeners are discussed.

PMID- 15478434
TI  - Spectral loudness summation and simple reaction time.
AB  - The present study evaluates the relation between loudness and simple reaction
      time (RT). Loudness matches between a narrowband noise (125 Hz wide) and a
      broadband noise (1500 Hz) were made at levels from near threshold to near 100 dB
      SPL. Over a similarly wide range of levels, RT to each of the noise bands was
      also measured. As reported often in previous loudness-matching studies, loudness
      summation depended strongly on level. With increasing SPL, the level difference
      between the noises needed to keep them equally loud first increased, to around 10
      dB at moderate levels, and then decreased. Except for one listener, the RT data
      show the same pattern. The level difference needed to keep RT to the two noises
      the same first increased and then decreased. These results show that RT is
      closely related to loudness, but not to sensation level. If RT depended on
      sensation level, the level difference between the two noises needed to achieve
      equal RT would not change with SPL because the difference in sensation level
      between two sounds is a constant. Overall, the average results provide strong
      support for the contention that simple RT and loudness are closely related.

PMID- 15478435
TI  - Masked auditory thresholds in sciaenid fishes: a comparative study.
AB  - Western Atlantic sciaenids comprise a taxonomically diverse teleost family with
      significant variations in the relationship between the swim bladder and the otic
      capsule. In this study, the auditory brainstem response (ABR) was used to test
      the hypothesis that fishes with different peripheral auditory structures (black
      drum, Pogonias chromis and Atlantic croaker, Micropogonias undulatus) show
      differences in frequency selectivity. In a black drum the swim bladder is
      relatively distant from the otic capsule while the swim bladder in Atlantic
      croaker possesses anteriorly-directed diverticulas that terminate relatively near
      the otic capsule. Signals were pure tones in the frequency range, 100 Hz to 1.5
      kHz, and thresholds were determined both with and without the presence of
      simultaneous white noise at two intensity levels (124 dB and 136 dB, re: 1
      microPa). At the 124 dB level of white noise background, both the black drum and
      Atlantic croaker showed similar changes in auditory sensitivity. However, in the
      presence of the 136 dB white noise masker, black drum showed significantly
      greater shifts in auditory thresholds between 300 and 600 Hz. The results
      indicate that the two species differ in frequency selectivity since the Atlantic
      croaker was less susceptible to auditory threshold shifts, particularly at the
      higher level of masking. This difference may be linked to peripheral auditory
      mechanisms.

PMID- 15478436
TI  - The discrimination of baboon grunt calls and human vowel sounds by baboons.
AB  - The ability of baboons to discriminate changes in the formant structures of a
      synthetic baboon grunt call and an acoustically similar human vowel (/epsilon/)
      was examined to determine how comparable baboons are to humans in discriminating
      small changes in vowel sounds, and whether or not any species-specific advantage
      in discriminability might exist when baboons discriminate their own
      vocalizations. Baboons were trained to press and hold down a lever to produce a
      pulsed train of a standard sound (e.g., /epsilon/ or a baboon grunt call), and to
      release the lever only when a variant of the sound occurred. Synthetic variants
      of each sound had the same first and third through fifth formants (F1 and F3-5),
      but varied in the location of the second formant (F2). Thresholds for F2
      frequency changes were 55 and 67 Hz for the grunt and vowel stimuli,
      respectively, and were not statistically different from one another. Baboons
      discriminated changes in vowel formant structures comparable to those
      discriminated by humans. No distinct advantages in discrimination performances
      were observed when the baboons discriminated these synthetic grunt vocalizations.

PMID- 15478437
TI  - Localization ability with bimodal hearing aids and bilateral cochlear implants.
AB  - After successful cochlear implantation in one ear, some patients continue to use
      a hearing aid at the contralateral ear. They report an improved reception of
      speech, especially in noise, as well as a better perception of music when the
      hearing aid and cochlear implant are used in this bimodal combination. Some
      individuals in this bimodal patient group also report the impression of an
      improved localization ability. Similar experiences are reported by the group of
      bilateral cochlear implantees. In this study, a survey of 11 bimodally and 4
      bilaterally equipped cochlear implant users was carried out to assess
      localization ability. Individuals in the bimodal implant group were all provided
      with the same type of hearing aid in the opposite ear, and subjects in the
      bilateral implant group used cochlear implants of the same manufacturer on each
      ear. Subjects adjusted the spot of a computer-controlled laser-pointer to the
      perceived direction of sound incidence in the frontal horizontal plane by
      rotating a trackball. Two subjects of the bimodal group who had substantial
      residual hearing showed localization ability in the bimodal configuration,
      whereas using each single device only the subject with better residual hearing
      was able to discriminate the side of sound origin. Five other subjects with more
      pronounced hearing loss displayed an ability for side discrimination through the
      use of bimodal aids, while four of them were already able to discriminate the
      side with a single device. Of the bilateral cochlear implant group one subject
      showed localization accuracy close to that of normal hearing subjects. This
      subject was also able to discriminate the side of sound origin using the first
      implanted device alone. The other three bilaterally equipped subjects showed
      limited localization ability using both devices. Among them one subject
      demonstrated a side-discrimination ability using only the first implanted device.

PMID- 15478438
TI  - Flow separation in a computational oscillating vocal fold model.
AB  - A finite-volume computational model that solves the time-dependent glottal
      airflow within a forced-oscillation model of the glottis was employed to study
      glottal flow separation. Tracheal input velocity was independently controlled
      with a sinusoidally varying parabolic velocity profile. Control parameters
      included flow rate (Reynolds number), oscillation frequency and amplitude of the
      vocal folds, and the phase difference between the superior and inferior glottal
      margins. Results for static divergent glottal shapes suggest that velocity
      increase caused glottal separation to move downstream, but reduction in velocity
      increase and velocity decrease moved the separation upstream. At the fixed
      frequency, an increase of amplitude of the glottal walls moved the separation
      further downstream during glottal closing. Increase of Reynolds number caused the
      flow separation to move upstream in the glottis. The flow separation cross
      sectional ratio ranged from approximately 1.1 to 1.9 (average of 1.47) for the
      divergent shapes. Results suggest that there may be a strong interaction of rate
      of change of airflow, inertia, and wall movement. Flow separation appeared to be
      "delayed" during the vibratory cycle, leading to movement of the separation point
      upstream of the glottal end only after a significant divergent angle was reached,
      and to persist upstream into the convergent phase of the cycle.

PMID- 15478439
TI  - Sound generation by steady flow through glottis-shaped orifices.
AB  - Although the signature of human voice is mostly tonal, it also includes a
      significant broadband component. Quadrupolelike sources due to turbulence in the
      region downstream of the glottis, and dipolelike sources due to the force applied
      by the vocal folds onto the surrounding fluid are the two primary broadband sound
      generating mechanisms. In this study, experiments were conducted to characterize
      the broadband sound emissions of confined stationary jets through rubber orifices
      formed to imitate the approximate shape of the human glottis at different stages
      during one cycle of vocal fold vibrations. The radiated sound pressure spectra
      downstream of the orifices were measured for varying flow rates, orifice shapes,
      and gas mixtures. The nondimensional sound pressure spectra were decomposed into
      the product of three functions: a source function F, a radiation efficiency
      function M, and an acoustic response function G. The results show that, as for
      circular jets, the quadrupole source contributions dominated for straight and
      convergent orifices. For divergent jets, whistling tonal sounds were emitted at
      low flow rates. At high flow rates for the same geometry, dipole contributions
      dominated the sound radiated by free jets. However, possible source-load acoustic
      feedback may have hampered accurate source identification in confined flows.

PMID- 15478440
TI  - An acoustic description of the vowels of Northern and Southern Standard Dutch.
AB  - A database is presented of measurements of the fundamental frequency, the
      frequencies of the first three formants, and the duration of the 15 vowels of
      Standard Dutch as spoken in the Netherlands (Northern Standard Dutch) and in
      Belgium (Southern Standard Dutch). The speech material consisted of read
      monosyllabic utterances in a neutral consonantal context (i.e., /sVs/).
      Recordings were made for 20 female talkers and 20 male talkers, who were
      stratified for the factors age, gender, and region. Of the 40 talkers, 20 spoke
      Northern Standard Dutch and 20 spoke Southern Standard Dutch. The results
      indicated that the nine monophthongal Dutch vowels /a [see symbol in text]
      epsilon i I [see symbol in text] u y Y/ can be separated fairly well given their
      steady-state characteristics, while the long mid vowels /e o o/ and three
      diphthongal vowels /epsilon I [see symbol in text]u oey/ also require information
      about their dynamic characteristics. The analysis of the formant values indicated
      that Northern Standard Dutch and Southern Standard Dutch differ little in the
      formant frequencies at steady-state for the nine monophthongal vowels. Larger
      differences between these two language varieties were found for the dynamic
      specifications of the three long mid vowels, and, to a lesser extent, of the
      three diphthongal vowels.

PMID- 15478441
TI  - The acoustic analysis of tone differentiation as a means for assessing tone
      production in speakers of Cantonese.
AB  - This paper reports on a methodology for acoustically analyzing tone production in
      Cantonese. F0 offset versus F0 onset are plotted for a series of tokens for each
      of the six tones in the language. These are grouped according to tone type into a
      set of six ellipses. Qualitative visual observations regarding the degree of
      differentiation of the ellipses within the tonal space are summarized numerically
      using two indices, referred to here as Index 1 and Index 2. Index 1 is a ratio of
      the area of the speaker's tonal space and the average of the areas of the
      ellipses of the three target tones making up the tonal space. Index 2 is a ratio
      of the average distance between all six tonal ellipses and the average of the sum
      of the two axes for all six tone ellipses. Using this methodology, tonal
      differentiation is compared for three groups of speakers; normally hearing
      adults; normally hearing children aged from 4-6 years; and, prelinguistically
      deafened cochlear implant users aged from 4-11 years. A potential conundrum
      regarding how tone production abilities can outstrip tone perception abilities is
      explained using the data from the acoustic analyses. It is suggested that young
      children of the age range tested are still learning to normalize for pitch level
      differences in tone production. Acoustic analysis of the data thus supports
      results from tone perception studies and suggests that the methodology is
      suitable for use in studies investigating tone production in both clinical and
      research contexts.

PMID- 15478442
TI  - Integration across frequency bands for consonant identification.
AB  - A comparison of the predictions of models of integration to data on the reception
      of consonants filtered into a variety of frequency bands is reported. New data on
      the consonant identification are presented. Three experiments were conducted
      testing the following bands: experiment I, 0-2100 Hz and 2100-4500 Hz; experiment
      II, 0-700 Hz combined with 700-1400, 1400-2100, 2100-2800, and 2800-4500 Hz;
      experiment III, all combinations of 700-1400, 1400-2100, 2100-2800, and 2800-4500
      Hz. The predictions of four models, Fletcher's [Speech and Hearing in
      Communication (Van Nostrand, New York, 1950)] independent errors model, Massaro's
      fuzzy logical model of perception [Proc. Int. Congress of Phonetic Sciences,
      Stockholm, Vol. 3, pp. 106-113 (1987)], and Braida's pre-labelling and post
      labelling models of integration [Q. J. Exp. Psychol. A 43, 647-677 (1991)], were
      compared in terms of their ability to predict combined-band scores. At least two
      models were capable of predicting performance for each combined-band condition.
      For experiment I, all models were able to make satisfactory predictions. For
      experiment II, a variant of the pre-labelling model was able to make satisfactory
      predictions. For experiment III, no model was able to make satisfactory
      predictions, but the fuzzy logical model of perception and a variant of the pre
      labelling model made relatively good predictions. Thus the ability of the models
      to predict performance depended more on whether the condition included the lowest
      frequency band than on the adjacency or frequency separation.

PMID- 15478443
TI  - Auditory discontinuities interact with categorization: implications for speech
      perception.
AB  - Behavioral experiments with infants, adults, and nonhuman animals converge with
      neurophysiological findings to suggest that there is a discontinuity in auditory
      processing of stimulus components differing in onset time by about 20 ms. This
      discontinuity has been implicated as a basis for boundaries between speech
      categories distinguished by voice onset time (VOT). Here, it is investigated how
      this discontinuity interacts with the learning of novel perceptual categories.
      Adult listeners were trained to categorize nonspeech stimuli that mimicked
      certain temporal properties of VOT stimuli. One group of listeners learned
      categories with a boundary coincident with the perceptual discontinuity. Another
      group learned categories defined such that the perceptual discontinuity fell
      within a category. Listeners in the latter group required significantly more
      experience to reach criterion categorization performance. Evidence of
      interactions between the perceptual discontinuity and the learned categories
      extended to generalization tests as well. It has been hypothesized that languages
      make use of perceptual discontinuities to promote distinctiveness among sounds
      within a language inventory. The present data suggest that discontinuities
      interact with category learning. As such, "learnability" may play a predictive
      role in selection of language sound inventories.

PMID- 15478444
TI  - Exploiting independent filter bandwidth of human factor cepstral coefficients in
      automatic speech recognition.
AB  - Mel frequency cepstral coefficients (MFCC) are the most widely used speech
      features in automatic speech recognition systems, primarily because the
      coefficients fit well with the assumptions used in hidden Markov models and
      because of the superior noise robustness of MFCC over alternative feature sets
      such as linear prediction-based coefficients. The authors have recently
      introduced human factor cepstral coefficients (HFCC), a modification of MFCC that
      uses the known relationship between center frequency and critical bandwidth from
      human psychoacoustics to decouple filter bandwidth from filter spacing. In this
      work, the authors introduce a variation of HFCC called HFCC-E in which filter
      bandwidth is linearly scaled in order to investigate the effects of wider filter
      bandwidth on noise robustness. Experimental results show an increase in signal-to
      noise ratio of 7 dB over traditional MFCC algorithms when filter bandwidth
      increases in HFCC-E. An important attribute of both HFCC and HFCC-E is that the
      algorithms only differ from MFCC in the filter bank coefficients: increased noise
      robustness using wider filters is achieved with no additional computational cost.

PMID- 15478445
TI  - Evaluation of formant-like features on an automatic vowel classification task.
AB  - Numerous attempts have been made to find low-dimensional, formant-related
      representations of speech signals that are suitable for automatic speech
      recognition. However, it is often not known how these features behave in
      comparison with true formants. The purpose of this study was to compare two sets
      of automatically extracted formant-like features, i.e., robust formants and HMM2
      features, to hand-labeled formants. The robust formant features were derived by
      means of the split Levinson algorithm while the HMM2 features correspond to the
      frequency segmentation of speech signals obtained by two-dimensional hidden
      Markov models. Mel-frequency cepstral coefficients (MFCCs) were also included in
      the investigation as an example of state-of-the-art automatic speech recognition
      features. The feature sets were compared in terms of their performance on a vowel
      classification task. The speech data and hand-labeled formants that were used in
      this study are a subset of the American English vowels database presented in
      Hillenbrand et al. [J. Acoust. Soc. Am. 97, 3099-3111 (1995)]. Classification
      performance was measured on the original, clean data and in noisy acoustic
      conditions. When using clean data, the classification performance of the formant
      like features compared very well to the performance of the hand-labeled formants
      in a gender-dependent experiment, but was inferior to the hand-labeled formants
      in a gender-independent experiment. The results that were obtained in noisy
      acoustic conditions indicated that the formant-like features used in this study
      are not inherently noise robust. For clean and noisy data as well as for the
      gender-dependent and gender-independent experiments the MFCCs achieved the same
      or superior results as the formant features, but at the price of a much higher
      feature dimensionality.

PMID- 15478446
TI  - A nonmusical paradigm for identifying absolute pitch possessors.
AB  - The ability to identify and reproduce sounds of specific frequencies is
      remarkable and uncommon. The etiology and defining characteristics of this skill,
      absolute pitch (AP), have been very controversial. One theory suggests that AP
      requires a specific type of early musical training and that the ability to encode
      and remember tones depends on these learned musical associations. An alternate
      theory argues that AP may be strongly dependent on hereditary factors and
      relatively independent of musical experience. To date, it has been difficult to
      test these hypotheses because all previous paradigms for identifying AP have
      required subjects to employ knowledge of musical nomenclature. As such, these
      tests are insensitive to the possibility of discovering AP in either nonmusicians
      or musicians of non-Western training. Based on previous literature in pitch
      memory, a paradigm is presented that is intended to distinguish between AP
      possessors and nonpossessors independent of the subjects' musical experience. The
      efficacy of this method is then tested with 20 classically defined AP possessors
      and 22 nonpossessors. Data from these groups strongly support the validity of the
      paradigm. The use of a nonmusical paradigm to identify AP may facilitate research
      into many aspects of this phenomenon.

PMID- 15478447
TI  - Detection of random alterations to time-varying musical instrument spectra.
AB  - The time-varying spectra of eight musical instrument sounds were randomly altered
      by a time-invariant process to determine how detection of spectral alteration
      varies with degree of alteration, instrument, musical experience, and spectral
      variation. Sounds were resynthesized with centroids equalized to the original
      sounds, with frequencies harmonically flattened, and with average spectral error
      levels of 8%, 16%, 24%, 32%, and 48%. Listeners were asked to discriminate the
      randomly altered sounds from reference sounds resynthesized from the original
      data. For all eight instruments, discrimination was very good for the 32% and 48%
      error levels, moderate for the 16% and 24% error levels, and poor for the 8%
      error levels. When the error levels were 16%, 24%, and 32%, the scores of
      musically experienced listeners were found to be significantly better than the
      scores of listeners with no musical experience. Also, in this same error level
      range, discrimination was significantly affected by the instrument tested. For
      error levels of 16% and 24%, discrimination scores were significantly, but
      negatively correlated with measures of spectral incoherence and normalized
      centroid deviation on unaltered instrument spectra, suggesting that the presence
      of dynamic spectral variations tends to increase the difficulty of detecting
      spectral alterations. Correlation between discrimination and a measure of
      spectral irregularity was comparatively low.

PMID- 15478448
TI  - Neuro-computational processing of moving sonar echoes classifies and localizes
      foliage.
AB  - Echoes from in situ tree trunks, similar to those observed by flying bats, are
      processed. A moving sonar converts echoes into spike sequences and applies neural
      computational methods to classify objects and estimate passing range. Two classes
      of tree trunks act as retro-reflectors that generate strong echoes (SEs),
      identified by a locally dense spike pattern. Linear drive-by sonar trajectories
      cause SEs to follow hyperbolic curves specified by passing range. A glint is a
      collection of consecutive range readings matching expected values on a specific
      hyperbolic curve. Passing-range detectors compare successive SE data with
      expected values in a table and tally coincidences. Counters increment when
      coincidences occur and decrement when they do not. A glint terminates after
      tallying a sufficient number of coincidences and coincidence failure occurs in
      the maximum-count detector. Reflector roughness, deviations in sonar trajectory,
      and echo jitter necessitate a coincidence window to define matches. Short windows
      identify small glints over piecewise linear sonar trajectories, while long
      windows accommodate deviations in sonar speed and trajectory, and associate
      multiple glints observed with shorter windows. The minimum coincidence window
      size yielding glints classify smooth and rough retro-reflectors.

PMID- 15478449
TI  - Study of acoustic nonlinearity parameter imaging methods in reflection mode for
      biological tissues.
AB  - Three novel methods for acoustic nonlinearity parameter B/A imaging in reflection
      mode are developed in this paper. They are: (1) the acoustic nonlinearity
      parameter B/A tomography by detecting reflective second harmonic wave, (2) the
      B/A tomography in reflection mode via the measurement of the difference frequency
      wave generated by a parametric array, and (3) the C-scan imaging of B/A via the
      measurement of the echo second-harmonic signal. A theoretical analysis and the
      experimental imaging of normal and pathological biological tissues by using these
      methods are also present and discussed. Results show that using the acoustic
      nonlinearity parameter imaging we can more easily distinguish the diseased tissue
      from the normal one than using the linear acoustic parameters.

PMID- 15478450
TI  - Estimated transmission beam pattern of clicks recorded from free-ranging white
      beaked dolphins (Lagenorhynchus albirostris).
AB  - Recordings were made from white-beaked dolphins in Icelandic waters using a four
      hydrophone array in a star configuration. The acoustic signals were amplified and
      sampled to a hard disk at a rate of 800 kHz per channel. The 3 and 10 dB
      beamwidths were calculated to be 8 degrees and 10 degrees, respectively,
      indicating a narrower transmission beam for white-beaked dolphins than that
      reported for bottlenose dolphins (Tursiops truncatus). The beamwidth was more
      similar to that found for belugas (Delphinapterus lucas). The measured beam
      pattern included large side lobes, perhaps due to the inclusion of off-axis
      clicks, even after applying several criteria to select only on-axis clicks. The
      directivity index was calculated to be 18 dB when using all data for angles from
      0 degrees-50 degrees. The calculated sound radiation from a circular piston with
      a radius of 6 cm driven by a white-beaked dolphin click had a beam pattern very
      similar to the measured beam pattern for the main transmission lobe of the white
      beaked dolphin. The directivity index was 29 dB. This is the first attempt to
      estimate the directionality index of dolphins in the field.

PMID- 15478452
TI  - Editorial: Complexity and future of biochemical differential diagnosis in
      psychiatry.

PMID- 15478451
TI  - Correlation of ultrasonic scatterer size estimates for the statistical analysis
      and optimization of angular compounding.
AB  - Ultrasonic scatterer size estimates generally have large variances due to the
      inherent noise of spectral estimates used to calculate size. Compounding
      partially correlated size estimates associated with the same tissue, but produced
      with data acquired from different angles of incidence, is an effective way to
      reduce the variance without making dramatic sacrifices in spatial resolution.
      This work derives theoretical approximations for the correlation between these
      size estimates, and the coherence between their associated spectral estimates, as
      functions of ultrasonic system parameters. A Gaussian spatial autocorrelation
      function is assumed to adequately model scatterer shape. Both approximations
      compare favorably with simulation results, which consider validation near the
      focus. Utilization of the correlation/coherence expressions for statistical
      analysis and optimization is discussed. Approximations, such as the invariance of
      phase and amplitude terms with angle, are made to obtain closed-form solutions to
      the derived spectral coherence near the focus and permit analytical optimization
      analysis. Results indicate that recommended parameter adjustments for performance
      improvement generally depend upon whether, for the system under consideration,
      the primary source of change in total coherence with rotation is phase term
      variation due to the change in the relative position of scattering sites, or
      field amplitude term variation due to beam movement.

PMID- 15478453
TI  - Are psychotherapists consistent in their ethical attitude to patient
      confidentiality?
AB  - BACKGROUND: The issue of confidentiality often causes an ethical dilemma for the
      psychotherapist. AIMS OF THE STUDY: We investigated if therapists are consistent
      in their attitude to confidentiality or judge each case on its own merit.
      METHODS: A questionnaire consisting of a series of clinical vignettes
      representing different ethical dilemmas in confidentiality in psychotherapy was
      completed by 93 therapists of different professional backgrounds and by a control
      group of 55 students from the fields of law and the humanities. RESULTS: Subjects
      in both groups were inconsistent in their attitude to confidentiality in two
      thirds of cases, and most of the participants based their decisions on the
      particular history and circumstances of each case. CONCLUSION: The rules guiding
      psychotherapists for the disclosure of confidential information are unclear.
      These findings failed to pinpoint a common denominator to explain the manner in
      which professionals handle information that may demand a break of
      confidentiality.

PMID- 15478454
TI  - Attitudes and opinions on corporal punishment among urban Israeli Jews.
AB  - Corporal punishment of children constitutes a human rights violation and has
      mental health consequences, yet it is frequently practiced in many countries. The
      objectives of this study were to identify attitudes and opinions with regard to
      corporal punishment among urban Jewish Israelis. Corporal punishment was defined
      as the means to discipline children by the use of physical force. A short battery
      of questions exploring attitudes and opinions on the use of corporal punishment
      of children was added to a periodic survey conducted by a private polling
      organization. The sample included 1,000 urban Jewish Israeli community residents.
      Most respondents did not endorse corporal punishment. However, when confronted
      with a question tapping the readiness of adults to comply with a ruling by the
      Supreme Court that prohibits the use of corporal punishment at home, most
      respondents expressed skepticism that the public will comply. Forty percent
      thought that most parents would agree to undergo training in the use of
      alternative means of discipline. Fifty-seven percent experienced physical
      punishment when growing up, a variable which was associated with all responses
      favoring its use as a means of discipline. The results of the study provide the
      bases for public health action, including training programs on alternative
      methods of discipline. Further research targeting other population groups not yet
      explored is needed.

PMID- 15478455
TI  - Trauma and dissociation in psychiatric outpatients.
AB  - BACKGROUND: We investigated the prevalence of exposure to traumatic events, the
      prevalence of post-traumatic suffering and dissociative symptoms, and the
      relationship between type of trauma and dissociation in a large sample of
      outpatient adults (ages 18-65) seeking treatment at an urban ambulatory mental
      health clinic in Jerusalem (N = 298). METHOD: Study participants completed self
      report measures regarding trauma history, post-traumatic symptoms of intrusion
      and avoidance phenomena, and both psychological and somatic dissociative
      phenomena. RESULTS: 98% of our sample reported experiencing at least one lifetime
      traumatic event, 83% of subjects who completed the Impact of Events Scale
      reported high levels of intrusion and avoidance symptoms, and 15% of the sample
      reported high levels of dissociative phenomena. Elevated dissociation was
      associated with physical and sexual abuse, particularly early childhood abuse, as
      well as increased prevalence of lifetime traumatic events. Diagnoses did not
      reflect the high levels of post-traumatic and dissociative symptoms. CONCLUSIONS:
      Our findings indicate the need for increased awareness and improved screening of
      traumatic exposure and its psychological impact upon psychiatric outpatients.

PMID- 15478456
TI  - Insight and alexithymia in hospitalized psychiatric patients.
AB  - The relationship of insight to the personality dimension of alexithymia was
      investigated in 91 psychiatric inpatients. Insight as a global construct and
      three subscales: the capacity to recognize that one has a psychiatric disorder,
      one needs treatment, and to label one's emotional illness as pathological were
      empirically measured via the Birchwood Scale for Insight. Alexithymia and its
      three subfactors were assessed by the 26-item Toronto Alexithymia Scale. Two of
      the alexithymia subfactors did correlate with reduced global insight and less
      acceptance of the need for therapy. Insight also correlated positively with the
      magnitude of depressed mood. In a regression model, depressed mood best predicted
      global insight. Other clinical variables, such as clinical severity upon
      admission, change in clinical status or diagnosis, did not predict insight
      levels. In summary, insight is a multidimensional phenomenon that does not simply
      correlate with alexithymia as a global construct but does correlate with
      alexithymic subfactor of diminished fantasy life.

PMID- 15478457
TI  - Relationship between alexithymia, dissociation and anxiety in psychiatric
      outpatients from Turkey.
AB  - Several studies have examined the relationship between dissociation and
      alexithymia. In this study, the objective was to investigate whether there was a
      relationship between alexithymia, dissociation and state and trait anxiety in
      psychiatric outpatients. The evaluations of psychiatric outpatients (n=154) were
      based on the Toronto Alexithymia Scale, the Dissociative Experiences Scale and
      the State and Trait Anxiety Index. The data were analyzed using chi2 test and
      multiple covariance analyses. Subjects with alexithymia (46.8%) were
      significantly less educated and showed higher state and trait anxiety. The mean
      Toronto Alexithymia Scale total score of the female and male patients was
      similar. The mean Dissociative Experiences Scale score of the study group was
      10.8 (sd=9.8, ranged 0 to 45). A multivariate analysis of covariance showed that
      state and trait anxiety was a significant covariant for the Toronto Alexithymia
      Scale-Difficulty Identifying Feelings subscale. Only the trait anxiety was a
      significant covariant for the Toronto Alexithymia Scale-Difficulty Expressing
      Feelings subscale. The overall main effect of dissociation was not significant on
      the Toronto Alexithymia Scale total and subscales. These data suggest that
      dissociation is fundamentally a different construct from alexithymia, while state
      and trait anxiety are closely related to alexithymia.

PMID- 15478458
TI  - Contribution of neuropsychology to epilepsy surgery.
AB  - Surgical treatment is being used with increasing frequency for patients with
      intractable epilepsy. Operative success depends to a large degree on the results
      of a comprehensive pre-operative patient evaluation the main purpose of which is
      to delineate the epileptogenic lesion. The pre-operative assessment includes
      video EEG monitoring, structural and functional (fMRI) neuroimaging and
      neuropsychological evaluation. The likelihood of the success of surgery is
      increased when all test results point to a single epileptogenic focus. The unique
      contribution of neuropsychology, which includes standard neuropsychological
      assessment and intracarotid sodium amytal (Wada) testing, is its capability to
      predict lateralization and often localization of a brain lesion based on
      cognitive function and dysfunction, which can be demonstrated also in the absence
      of a structural lesion. The Wada test is used to determine the cerebral speech
      dominance, to predict postsurgical amnesia and is found to be useful in
      predicting laterality of seizure focus in candidates for temporal lobectomy.

PMID- 15478459
TI  - Comparing aspects of mental health legislation of Israel and Massachusetts.
AB  - This paper compares the manner in which two sets of mental health laws, that of
      Massachusetts, U.S.A., and that of the State of Israel, deal with specific areas
      of civil enforced commitment. The definition of psychiatric disorder that
      justifies commitment is broader in Massachusetts, in Israel psychosis alone is
      considered, excluding conditions such as severe non-psychotic depression,
      obsessive-compulsive disorder and anorexia. In Israel, commitment is possible
      only when there is a risk of danger that is immediate. In Massachusetts, only a
      judge can make decisions beyond the first four days, while in Israel they are
      made by a District Psychiatrist. Unlike Massachusetts, there is no possibility of
      enforced commitment of alcoholics or drug addicts in Israel, even in the presence
      of impaired judgement and severe family distress. The changing trends are
      presented, as Israel seems to be drawing slowly toward the Massachusetts position
      in some of these issues. The role of consumers in these processes is considered,
      as is the possibility of enforced commitment of people with severe personality
      disorders.

PMID- 15478460
TI  - Personality disorders as grounds for reduced sentence in murder cases.
AB  - Clause 300 A (A) of the Israel penal code stipulates that severe mental disorder
      may serve as grounds for reduced sentence in cases of murder. There is an
      unresolved debate in the forensic psychiatric field whether severe personality
      disorders are included in this category. We present a set of criteria for
      applying this clause to offenders with personality disorder and demonstrate
      through three cases how these criteria can be used. All three cases had the
      following basic characteristics: A. Established diagnosis of severe personality
      disorder on the basis of historical data from multiple sources and in accordance
      with the evidence presented to the court. B. Presentation of a coherent
      description of the content of the murder as it directly affected the offender's
      severe impairment, with a strong link between the pathology and the offender's
      reduced capacity to understand or avoid the act. C. Establishment of the
      significantly limiting impact of the personality disorder on the offender's
      capacity to avoid the act, as based on the evidence presented to the court. We
      conclude that guidelines for formulating the psychiatric assessment and court
      report are feasible and necessary in these cases. Further experience in this area
      is needed until definite conclusions can be reached. Further studies are needed
      to confirm the suitability of this method.

PMID- 15478461
TI  - The forensic psychiatric corner.

PMID- 15478462
TI  - Hypothetical structure of human serum amyloid A protein.
AB  - The proteins known as serum amyloid A (SAA) play major, but relatively
      uncharacterized, roles in the acute phase response and are important components
      of the innate immune system of humans and probably all vertebrates. N-terminal
      fragments of the inducible isoforms, SAA1 and SAA2, are the major constituents of
      fibrils formed during secondary or reactive amyloidosis. Little is known about
      the structure of SAA beyond secondary structure analyses and circular dichroism
      spectroscopic data indicating significant alpha helix conformation. Analysis of
      the primary structure of human SAA indicates probable homology to the N-terminal
      domain of hemocyanins of arthropods and suggests that approximately 80% of the
      molecule may consist of a helical bundle with the remaining portion of the C
      terminus potentially disordered. This model of SAA suggests that proposed binding
      sites for laminin, fibronectin, and calcium are segregated to one face of the
      molecule and that the heparin/heparan binding site is found in the putatively
      disordered region of the protein. It is possible that removal of the N-terminal
      76 amino acid fragment by proteolytic cleavage found generates an unstable entity
      that undergoes a helix to beta strand transition analogous to the fibril process
      of A-beta and prion peptides.

PMID- 15478463
TI  - Amyloidogenic hexapeptide fragment of medin: homology to functional islet amyloid
      polypeptide fragments.
AB  - Medin is the main constituent of aortic medial amyloid that occurs in virtually
      all individuals older than sixty. It is derived from a proteolytic fragment of
      lactadherin, a mammary epithelial cell expressed glyco-protein that is secreted
      as part of the milk fat globule membrane. It was previously demonstrated that an
      octapeptide fragment of medin (NH2-NFGSVQFV-COOH) forms typical well-ordered
      amyloid fibrils. To obtain further insights into the molecular determinants that
      mediate this process by such a short peptide fragment, we examined the
      amyloidogenic potential of its truncated forms and analogues. Our results clearly
      indicated that a truncated fragment of medin, the hexapeptide, NFGSVQ can form
      typical amyloid fibrils. A shorter pentapeptide fragment, NFGSV, self-assembled
      into a gel structure that exhibited a network of fibrous structures. The amyloid
      forming NFGSVQ hexapeptide is noticeably similar to the short amyloidogenic
      peptide fragments of the islet amyloid polypeptide (IAPP), NFGAIL and NFLVH.
      Moreover, the substitution of the phenylalanine residue with either alanine or
      isoleucine significantly reduced the amyloidogenic potential of the peptide
      fragment. Taken together, the results are consistent with the assumed role of
      stacking interactions in the self-assembly processes that lead to the formation
      of amyloid fibrils. The results are discussed in the context of models for the
      mechanism of fibril formation and ways to design inhibitors.

PMID- 15478464
TI  - Histochemical accumulation of oxidative damage products is associated with
      Alzheimer-like pathology in the canine.
AB  - An important lesion in Alzheimer's disease (AD) patient brains is the
      neurofibrillary tangle (NFT). Hyperphosphorylated tau is its major component. In
      a former paper we described some NFT in the canine brain. During aging, moreover,
      advanced glycation end products (AGE) might accumulate. Glycated tau induces
      lipid peroxidation in vivo and tau and AGE antigens have been mentioned to co
      localize in NFT. This indicates that AGE may play an important role in Alzheimer
      disease (AD) by oxidation of tau. The aim of the present study was to investigate
      amyloid, neurofibrillary tangles, Abeta precursor protein, Abeta, tau, ubiquitin,
      advanced glycation end products, 4-hyroxynonenal protein and lipofuscin in a
      series of dogs of varying ages. The results showed a significant positive
      correlation between age and amyloid quantity (Congo red staining), HNE staining
      and lipofuscin (LF), and between amyloid quantity and HNE staining and LF.
      Staining for AbetaPP seemed to have a tendency to increase with age, whereas
      staining for tau, ubiquitin and AGE each only gave limited positive results in a
      proportion of the older dogs. Preliminary studies including loss of cognitive
      capabilities in the older dogs and chemical measurement of lipofuscin-like
      pigment (LFP) accumulation in brain extracts revealed an increase with old age
      and dementia. The Congo red, HNE and LF results suggest that deposition of
      amyloid with aging might be associated with formation of end products of lipid
      peroxidation. The finding of the limited positive signals for tau, ubiquitin and
      AGE in some old cases might indicate that the spontaneous brain pathology of the
      aged dog reveals similarities to early stages observed in AD in humans especially
      those with Down syndrome.

PMID- 15478465
TI  - Serum amyloid P component in mink, a non-glycosylated protein with affinity for
      phosphorylethanolamine and phosphorylcholine.
AB  - Experimental AA amyloidosis in the mink is used as a model for the amyloid
      disease process. In that context it is important to characterize the different
      proteins involved in the amyloid formation. In the present work, we have
      characterized the serum amyloid P component (SAP) in mink. SAP was purified from
      serum by affinity chromatography using phosphorylethanolamine-coupled ECH
      sepharose 4B. SDS-PAGE showed one major protein band (approximately 26 kDa)
      together with one minor band (10% of the major band) with a higher molecular mass
      (approximately 30 kDa) corresponding to a non-glycosylated and a glycosylated
      variant. All SAP molecules elucidated so far have at least one major subunit that
      is heavily glycosylated. It is therefore the first time that a non-glycosylated
      SAP protein is found in a mammalian species. The amino acid sequence was
      established using Edman degradation and mass spectrometry. As expected, the
      protein showed high homology with the other mammalian SAP molecules, ranging from
      73% (human) to 63% (mouse). The SAP protein showed affinity for phosphorylcholine
      and thus expressed CRP-like properties.

PMID- 15478466
TI  - The amino acid sequence of a glycosylated AL-chain from a patient with primary
      amyloidosis.
AB  - An amyloid fibril protein (Owe) related to primary amyloidosis was found to be a
      glycosylated complete immunoglobulin light chain (AL). The amino acid sequence
      revealed a protein composed of 214 residues and with a glycosylation site in
      position 20. The sequence established an AL V-region corresponding to a kappa 1b
      germline gene, but differs from that in 12 positions. Eight of them are in the FR
      regions, positions 7, 13, 20, 42, 46, 60, 76 and 79. The J-segment is that of
      JkappaII.

PMID- 15478467
TI  - Deposition of transthyretin amyloid is not accelerated by the same amyloid in
      vivo.
AB  - Acceleration of amyloid deposition by administration of amyloid fibrils and
      transmissibility of disease have been reported in several types of amyloidoses.
      Families with a variant transthyretin (TTR V30M)-associated familial amyloidotic
      polyneuropathy (FAP) exhibit genetic anticipation, with TTR V30M-amyloid
      depositing at an earlier age in successive generations. The molecular bases of
      anticipation in FAP have remained to be determined. We asked if administration of
      TTR-amyloid fibrils (ATTR) extracted from the heart of an FAP TTR V30M patient
      would accelerate ATTR deposition in transgenic mice expressing the human mutant
      ttr gene responsible for FAP TTR V30M and indeed the administration did
      accelerate deposition of apolipoprotein A-II-amyloid fibrils (AApoAII), and not A
      TTR. Our experiments present, for the first time, evidence that the degree of
      inducibility of ATTR is low relative to AApoAII and we suggest that
      administration of ATTR may not explain the genetic anticipation which occurs in
      FAP.

PMID- 15478468
TI  - An unusual transthyretin gene missense mutation (TTR Phe33Val) linked to familial
      amyloidotic polyneuropathy.
AB  - Familial amyloidotic polyneuropathy is a rare autosomal dominant disease, with
      clinical symptoms beginning in most kindreds within the third to seventh decades
      of life. The primary defect results from one of a number of mutations in the
      transthyretin (TTR) gene. Over 80 mutations in the TTR gene have been described.
      Most mutations give rise to adult onset progressive peripheral and autonomic
      neuropathy, due to amyloid deposition within the nerves, and often subclinical
      cardiac amyloid and vitreous deposits. We report here the clinical and molecular
      characterization of a rare TTR missense mutation discovered in a young woman from
      Macedonia, showing severe axonal sensory-motor polyneuropathy, restrictive
      cardiomyopathy and bilateral vitreous deposits. The transthyretin gene, analyzed
      by direct nucleotide sequencing, demonstrated a T to G transversion at nucleotide
      183 in the exon 2 which is predicted to cause a heterozygous valine for
      phenylalanine substitution at codon 33 (TTR Phe33Val). This mutation has been
      previously reported only twice, without complete clinical descriptions.

PMID- 15478469
TI  - Successful pregnancies and fatherhood in familial amyloidotic polyneuropathy (FAP
      Val30Met) patients with liver transplantation.
AB  - For familial amyloidotic polyneuropathy (FAP) patients, several problems
      regarding reproduction are present. For males, erectile dysfunction and
      retrograde ejaculation are well known complications of the disease In addition,
      the risk of transferring a fatal disease to their offspring is a matter of
      concern for the patients. For transplanted fertile patients, the risk of side
      effects of immunosupression therapy causing congenital malformations must be
      addressed, and for female patients the additional risk of complications during
      pregnancy and delivery is a case of concern. After delivery, the problem of
      breast-feeding arises. In the Swedish population of transplanted patients, five
      successful pregnancies, of which male FAP recipients fathered three, are
      reported. All patients were on stable immunosuppressive therapy with cyclosporine
      or tacrolimus and prednisolone. From our experience, successful fatherhood and
      pregnancy is possible for liver transplanted FAP patients, as it has been
      reported for patients transplanted for other medical reasons.

PMID- 15478470
TI  - IgM AL amyloidosis due to B cell lymphoproliferative disorder: efficacy of high
      dose melphalan followed by autologous stem cell transplantation.
AB  - This report concerns a patient with IgM AL amyloidosis due to a B cell
      lymphoproliferative disorder who was successfully treated with VAD and subsequent
      high-dose melphalan followed by autologous stem cell support. After this
      chemotherapeutic regimen, the patient showed complete hematological remission and
      improvement in nephrotic syndrome. These findings suggest that high-dose
      melphalan may also be effective for lymphoplasmacytoid cells producing monoclonal
      IgM which are phenotypically distinct from plasma cells. Myeloablative therapies,
      such as high-dose melphalan, should definitely be considered as a treatment
      option for AL amyloidosis, irrespective of the type of precursor immunoglobulin.

PMID- 15478471
TI  - Psychotropic medication in pregnancy: ethical aspects and clinical management.
AB  - This article explores the dilemma of whether women with mental illness should
      take potentially teratogenic psychotropic medications during pregnancy, from both
      the maternal and fetal perspectives. Ethical and social aspects of the dilemma
      are presented to assist perinatal and psychiatric practitioners to provide
      holistic and competent care to the mother/fetus dyad. Specific fetal risks
      involved with maternal psychotropic drug use are described and contrasted with
      fetal risks of an untreated, psychiatrically ill mother. Nursing and healthcare
      considerations for the care of this population are presented in general, and
      specific psychotropics are reviewed for their risk profile in pregnancy. The
      article concludes with a discussion of actions to reduce maternal and fetal risk
      for women who are mentally ill and are currently taking, or considering taking, a
      psychotropic medication.

PMID- 15478472
TI  - Living with genital herpes: how effective is antiviral therapy?
AB  - Twenty-five percent of American women and 20% of American men have genital
      herpes. Most of these individuals have never been diagnosed because of the
      prevalence of atypical clinical presentation and subclinical infection. This
      chronic, recurrent infection poses a significant public health challenge,
      particularly in women of childbearing age, who are at risk of transmitting the
      virus to their infants during pregnancy and birth, as well as to their discordant
      sexual partners. Antiviral therapy decreases the rate of recurrent episodes,
      decreases asymptomatic shedding of the virus, reduces the risk of transmission to
      sexual partners, and reduces the rate of operative delivery in women with a
      history of genital herpes. This article reviews the literature to explore
      evidence-based strategies for addressing the physical and psychological sequelae
      of herpes simplex virus infection and for accurately diagnosing and managing
      neonates who acquire this infection perinatally.

PMID- 15478473
TI  - The use of vaccines in pregnancy.
AB  - Adult immunization rates in the United States lag behind pediatric immunization
      rates. Healthcare providers in all settings should discuss immunization with
      their patients. There are concerns regarding the use of vaccine in women who are
      pregnant or breastfeeding. This article reviews selected vaccines and the use of
      vaccines in women who are pregnant or breastfeeding. Basic principles of vaccine
      administration are discussed as well as standards for immunization practice.
      Concerns regarding vaccine safety in any population are reviewed.

PMID- 15478474
TI  - Pharmacologic treatment of hypertensive disorders during pregnancy.
AB  - Pregnancy complicated by hypertension is a common problem faced by clinicians. It
      can lead to substantial maternal and/or fetal/neonatal morbidity and mortality.
      There are a variety of medications that can be used during pregnancy either for
      treatment of significant chronic hypertension or in cases of acute severe
      hypertension. Most antihypertensive drugs have been shown to be safe for use in
      pregnancy. A variety of medications are available to treat more severe
      hypertension, although the use of pharmacologic therapy to treat mild chronic
      hypertension during pregnancy has not been supported in the literature. The data
      are more limited concerning drugs that would be used in the event of hypertensive
      emergencies or in an intensive care setting; however, in such a situation,
      maternal health and life become paramount and, despite lack of good studies,
      appropriate treatment should be rendered.

PMID- 15478475
TI  - Strategic use of antibiotics in the neonatal intensive care unit.
AB  - Infection is one of the most common causes of infant morbidity and mortality in
      the neonatal intensive care unit, despite the availability of various therapeutic
      medical interventions, such as mechanical ventilation, that allow premature
      infants a better chance of survival. In fact, many of these therapeutic
      interventions violate the natural protective barriers for infection. Fortunately,
      maternal and neonatal risk factors have been identified for early- and late-onset
      sepsis and the prevalence of highly suspected pathogens for each type of
      infection influences the empiric selection of antibiotics. In many institutions,
      the common pathogens have developed resistance to antibiotics. In others, the
      predominance of pathogens has shifted. Both challenges may warrant modification
      of traditional antibiotic regimens. Continual monitoring of pathogen shifts
      within an individual neonatal intensive care unit and application of various
      antibiotic characteristics are key elements of strategic, safe, and effective use
      of antibiotics in this patient population. Development of a protocol
      incorporating infection control measures and guidelines for judicious use of
      antibiotics can minimize the threat of antibiotic resistance.

PMID- 15478476
TI  - Viral infection and antiviral therapy in the neonatal intensive care unit.
AB  - Viral diseases are leading causes of mortality and morbidity among infants
      requiring care in the neonatal intensive care unit (NICU), with ongoing
      discoveries of new viral pathology likely to add to the burdens posed. Many viral
      diseases in NICU infants are undiagnosed or appreciated only late in the course
      because of subtle or asymptomatic presentation, confusion with bacterial disease,
      and failure to consider viral disease. We present an overview of viral disease in
      NICU infants, with emphasis on pharmacologic agents currently employed for
      prophylaxis and treatment of such diseases. Advances in molecular biology and
      popular demand to develop antiviral agents for viral diseases (eg, human
      immunodeficiency virus) offer great promise for the future.

PMID- 15478478
TI  - Neonatal intensive care drug therapy update: a bibliography.

PMID- 15478477
TI  - Neonatal seizures: diagnosis, pharmacologic interventions, and outcomes.
AB  - Neonatal seizures are difficult to detect, diagnose, and manage. Infants with a
      history of seizures often have long-term neurologic sequelae. Controversy exists
      as to whether neonatal seizures themselves cause damage to the developing brain,
      and thus, subsequent sequelae; or if these sequelae are due primarily to the
      underlying cause of the seizures. Treatment of seizures involves identifying and
      treating the underlying etiology of the seizure and appropriate use of
      pharmacologic interventions. To provide the context for pharmacological
      management of seizures in newborns, this article examines the pathophysiology and
      etiology of seizures and discusses pharmacological agents and issues, short- and
      long-term outcomes, clinical implications, and directions for future research.
      Understanding pharmacological issues within this context provides a comprehensive
      foundation for decision making and management of neonatal seizures.

PMID- 15478479
TI  - In situ transformation of glass-ionomer into an enamel-like material.
AB  - PURPOSE: To assess the nature of clinically detectable alterations in glass
      ionomer after long-term clinical service. METHODS: In addition to clinical macro
      pictures, SEM was carried out on replicas and on two sectioned primary molars SEM
      EDAX analysis was performed to determine chemical transformation in the glass
      ionomer. Also with SEM-EDAX, the composition was determined of a partially
      removed half-year old sealant. RESULTS: The clinically observed altered optical
      aspect and increased hardness could be related with surface structure changes as
      identified by SEM. The changed glass-ionomer showed a continuous integration with
      the adjacent enamel. The SEM-EDAX analysis revealed an increase of calcium and
      phosphorus in the surface layer, tentatively suggesting a sort of additional
      "mineralization" of the material. This phenomenon was only observed for
      restorations that had minimally 2-3 years in vivo dwell time.

PMID- 15478480
TI  - Effect of three direct restorative materials on molar cuspal fracture resistance.
AB  - PURPOSE: This study compared the cusp fracture strength of molars restored using
      a condensable resin composite with that of teeth restored with conventional
      amalgam, a bonded amalgam, and an incrementally placed resin composite. METHODS:
      Standardized MOD cavity preparations (2/3 the buccal-lingual dimension x 4 mm
      deep) were made in 50 extracted human molars and restored as follows (n = 10):
      (1) a packable posterior resin composite; (2) an incrementally placed microfilled
      posterior resin composite; (3) a spherical particle amalgam alloy; (4) spherical
      amalgam with a dentin adhesive liner and (5) no restoration (preparation only;
      negative control). A sixth group of intact molars (n = 10) served as a positive
      control. Following storage and thermocycling, each specimen was tested for cuspal
      fracture strength. RESULTS: Cavity preparation reduced cuspal fracture strength
      by over 50%. The fracture strength of intact teeth was significantly greater than
      that of all other groups (P< 0.0001). None of the restorative procedures
      increased cuspal fracture resistance over that of prepared teeth.

PMID- 15478481
TI  - Relationship between S. mutans and the autofluorescence of carious dentin.
AB  - PURPOSE: To investigate the relationship between the presence of S. mutans and
      the autofluorescent signal detected in carious dentin, using confocal laser
      scanning microscopy. METHODS: Experiment 1:15 visually caries-free freshly
      extracted premolars were coated with varnish except for two 2 mm x 2 mm windows;
      five were subjected to a 15-day bacterial artificial caries system using
      Streptococcus mutans while 10 underwent a 7-day controlled, lactic acid (0.5 M,
      pH 2.7) demineralization protocol. At the end of both periods, all teeth were
      longitudinally sectioned and the 20 bacterial and 40 acid-induced artificial
      lesions were examined by confocal laser-scanning microscopy. The media containing
      the S. mutans was also examined for autofluorescence. Experiment 2: 20 750 microm
      thick caries-free coronal dentin disks were prepared from 10 healthy premolars.
      Ten underwent a demineralization protocol using 0.1 M EDTA (pH 4.8) for 21 days.
      All 20 were finally subjected to the same artificial bacterial caries system as
      above for 15 days and then examined for autofluorescence using confocal laser
      scanning microscopy. RESULTS: Experiment 1 results showed that acid-demineralized
      lesions did not generate any autofluorescence. Lesions created by the bacterial
      system did exhibit autofluorescence. The media with or without S. mutans did not
      exhibit autofluorescence. Experiment 2: bacteria-induced lesions on dentin that
      had previously been acid-demineralized generated a visibly stronger
      autofluorescence signal than those lesions grown on sound dentin. It is
      hypothesized that dentin demineralization during the carious process exposes more
      matrix to a bacteria-matrix interaction, thus generating or refining the matrix
      chromophore responsible for the autofluorescence signal detected in carious
      dentin.

PMID- 15478482
TI  - Wedged cervical lesions produced by toothbrushing.
AB  - PURPOSE: To compare the morphology of experimentally induced cervical toothbrush
      abrasion lesions to teeth demonstrating non-carious cervical lesions in vivo.
      METHODS: Eighteen premolars extracted for orthodontic reasons were each subjected
      to 80 hours (1.4 million strokes) of horizontal brushing in a custom fabricated
      toothbrushing machine. Toothpaste slurry was applied continuously and specimens
      were subjected to 300 gms of toothbrushing force. Denture base resin was used to
      simulate gingival recession of 1 mm and a sulcus width of 0.1 mm. Cervical
      abrasions were analyzed by optical and scanning electron microscopy and
      classified as either V-shape/wedged vs. U-shape/rounded lesions. When lesions
      exhibited both shapes, they were classified as mixed. Shapes of experimentally
      induced lesions then were compared to naturally occurring ones found on extracted
      premolars. RESULTSts: Experimentally induced toothbrush abrasion duplicated the
      classical clinical shapes. Half (9/18) of the experimentally induced toothbrush
      abrasions exhibited wedged lesions, 28% (5/18) showed a mixed wedged/rounded
      lesion, and 22% (4/18) showed rounded lesions. Serial photography showed
      progression of the morphology of the lesions. Toothbrush abrasion apparently
      begins apical to the cemento-enamel junction, progresses to dentin, and then
      undermines enamel with loss of the original cemento-enamel junction. Wedged
      lesions may appear with the apex oriented coronal or apical, or may be
      symmetrical.

PMID- 15478483
TI  - Argon laser irradiation and fluoride treatment effects on caries-like enamel
      lesion formation in primary teeth: an in vitro study.
AB  - PURPOSE: To evaluate topical acidulated phosphate fluoride (APF) and low fluence
      argon laser (Ar) treatment effects on in vitro caries formation in primary tooth
      enamel. METHODS: 20 extracted or exfoliated primary teeth with sound buccal and
      lingual surfaces underwent soft tissue debridement and a fluoride-free
      prophylaxis. Treatment groups were: (1) Control [n=5]; (2) Ar [231mW, 10 seconds,
      11.5J/cm2; n=5], (3) 1.23% APF for 4 minutes before Ar [n=5]; (4) Ar before APF
      [n=5]. Buccal and lingual enamel surfaces were treated, and then rinsed in
      deionized,distilled water (24 hours). An acid-resistant coating was applied
      leaving buccal and lingual sound enamel windows exposed. In vitro enamel caries
      was created (2.2 mM calcium, 2.2 mM phosphate, 5.0 mM fluoride, pH 3.90, 10
      days). Following longitudinal sectioning, two lesions per primary tooth (10
      lesions total) with each group were evaluated for lesion depth (polarized light,
      water imbibition) and compared (ANOVA, Duncan's Multiple Range). RESULTS: Argon
      laser irradiation alone provided a 41% reduction in lesion depth (176 +/- 21
      microm, P< 0.05) when compared with that for the no treatment controls (297 +/-
      31 microm). The combination of argon laser irradiation with APF treatment
      resulted in lesion depth decreases of slightly over 50% (140 +/- 23 microm for
      APF before ArTx; 124 +/- 17 microm for ArTx before APF, P< 0.05) compared with
      control lesion depths, and 20 to 30% over that for argon laser treatment alone
      (P< 0.05). There was no statistical difference in lesion depth regardless of
      whether fluoride treatment occurred before or after laser irradiation (P> 0.05).

PMID- 15478484
TI  - Remineralization effects of a sodium fluoride bioerodible gel.
AB  - PURPOSE: To evaluate the effectiveness of a 5% sodium fluoride (NaF) bioerodible
      gel to remineralize demineralized enamel. METHODS: Artificial enamel lesions were
      created at the gingivofacial surface of 36 extracted teeth. Longitudinal sections
      were obtained through the lesions, photographed under polarized light microscopy,
      and the demineralized areas were quantitated. Sections were painted with an acid
      protective varnish, leaving only the facial surface of the enamel lesion exposed,
      and positioned naturally into the tooth from which they were obtained. Teeth were
      randomly mounted in sets of four that simulated a natural anterior arch form.
      Equal numbers were subjected to a NaF gel, control gel dr received no treatment,
      with the gel being placed and retained by the interproximal embrasures of the
      teeth. Following 30 days exposure to artificial saliva, the lesions were
      photographed and quantitated in the same manner as prior to treatment. RESULTS:
      The NaF gel showed significantly more remineralization than the control groups
      (P< 0.05), with a 68.9% (+/- 17.7) mean lesion remineralization.

PMID- 15478485
TI  - Zirconate coupling agent for bonding resin luting cement to pure zirconium.
AB  - PURPOSE: To evaluate the shear bond strengths of two dual-cured resin luting
      cements to pure zirconium and the effect of zirconate coupling agent on the bond
      strength. METHODS: The two different-shaped pure zirconium specimens (99.9%) were
      untreated or treated with one of the four primers including zirconate coupler and
      then cemented together with one of the two dual-cured resin luting cements. Half
      of the specimens were stored in water at 37 degrees C for 24 hours and the other
      half thermocycled 20,000 times before shear bond strength testing. RESULTS:
      Regardless of the resin luting cement and thermocycling, specimens treated with
      the mixture of zirconate coupler and resin bonding agent showed the highest shear
      bond strength among the five treatments. Surface treatment with the mixture of
      zirconate coupler and resin bonding agent showed significantly greater shear bond
      strength compared with other treatments at 20,000 thermocycles. The application
      by the mixture of zirconate coupler and resin bonding agent on the pure zirconium
      metal surface appears to be effective for bonding between zirconium and dual
      cured resin luting cements.

PMID- 15478486
TI  - A two-year comparison of resin-based composite tunnel and Class II restorations
      in a randomized controlled trial.
AB  - PURPOSE: To evaluate the performance of total tunnel restoration with resin-based
      composites compared to Class II resin-based composite restorations in a
      randomized controlled clinical study. METHODS: 63 approximal carious lesions were
      restored in 38 patients by two experienced operators. The carious dentin and
      approximal demineralized enamel were completely removed for the tunnel
      restoration leaving the marginal ridge intact. The occlusal opening was enlarged
      to the center of the tooth to make access easy. Conservative cavity preparation
      was performed for the Class II restorations. All cavities were restored with
      Scotchbond Multipurpose Plus and Z250. At baseline, 1- and 2-year recalls, the
      restorations were evaluated clinically by two examiners using a modified USPHS
      rating system and radiographically for recurrent, caries. RESULTS: Both types of
      restorations performed well clinically, and there was no significant difference
      (P> 0.05) by the chi square test in any category. Recurrent caries was not
      detected. Only one tunnel restoration had to be replaced with a Class II
      restoration because of falling of the restoration with the marginal ridge after 2
      years. However, no significant difference in the survival rates (P> 0.05) could
      be demonstrated between the restorations by the log-rank test.

PMID- 15478487
TI  - Influence of marginal bevels on microleakage around Class V cavities bonded with
      seven self-etching agents.
AB  - PURPOSE: To evaluate microleakage around Class V resin-based composite
      restorations in box-shaped cavities with and without marginal bevels, bonded with
      one of seven self-etching materials and a non-self etching system. METHODS: 120
      extracted human premolars were randomly assigned to eight groups for bonding with
      the following self-etching agents: Prompt-L Pop, Adper Prompt, Clearfil SE,
      Prime& Bond NT with NRC, Xeno111, One-Up Bond, AdheSe, or Prime & Bond NT using a
      total etch technique (36% H2PO4). Box cavities were cut in both the lingual and
      buocal surfaces. The cavities were made with an ISO 010-fissure diamond bur in a
      water-cooled high-speed handpiece and were approximately 3 mm wide, 1.5 mm deep,
      and 2.0 mm high. Selected at random, box-shaped cavities were cut with a 0.5 mm
      bevel in enamel and dentin on one side and on the contra-lateral side, box-shaped
      cavities were cut without bevels. Each tooth served as its own control. The teeth
      were thermocycled and the specimens prepared and examined for microleakage using
      Procion Red as a marker. RESULTS: All gingival margins leaked whether or not a
      bevel had been placed, when bonded either with a self-etching agent or using a
      total etch technique with 36% phosphoric acid. There was no significant
      difference in leakage between the self-etching groups or those using a total etch
      technique, at the gingival bevel margins, (P= 0.7384) or the gingival non-beveled
      margins (P= 0.2307; Kruskal-Wallis Test). Microleakage was found with every
      agent, both occlusally and gingivally, when bonded either with a self-etching
      agent or using a total-etch technique. There was no significant difference in
      leakage between the self-etching groups or those using a total etch technique at
      the enamel bevel margins, (P= 0.9907) or the enamel non-beveled margins (P=
      0.9963; Kruskal-Wallis Test).

PMID- 15478488
TI  - Effect of finishing and polishing procedures on surface roughness, gloss and
      color of resin-based composites.
AB  - PURPOSE: To evaluate the effects of different finishing and polishing procedures
      on surface roughness, gloss and color of five resin composites: two experimental
      microhybrid composites - FZ-Dentin (FZD) and FZ-Enamel (FZE), one commercial
      microhybrid composite - Esthet-X (EX), and two microfilled composites -
      Heliomolar (HM) and Renamel Microfill (RM). METHODS: Surface roughness, gloss and
      color of the disc-shaped specimens (10 mm in diameter and 2-mm thick) were
      measured as Mylar (baseline), 16-fluted carbide bur and polishing were completed.
      Sixteen specimens of each composite were randomized to four groups of four. After
      finishing with a 16-fluted finishing bur, each group was polished by a different
      system: 1. Astropol (A), 2. Sof-lex disc (S), 3. Po-Go (P), 4. Enhance (E).
      Average surface roughness (Ra) was measured with a profilometer. Gloss
      measurements were performed using small-area glossmeter, while color coordinate
      values were recorded using a spectrophotometer. A deltaE*ab< or =1 was considered
      to be the limit of perceptibility. RESULTS: The order of surface roughness ranked
      according to polishing system (for all five composites together) was: P < S < E <
      A. The order of surface roughness ranked according to composites was: RM < FZD <
      FZ < HM < EX. The order of gloss ranked according to polishing system (for all
      five composites together) was: P > E > A > S. The order of gloss values for the
      polished composites (for each of four polishing systems) was: RM > FZD > FZE > HM
      > EX. Fisher's PLSD intervals at the 0.05 level of significance for comparisons
      of means of surface roughness among five composites and four polishing systems
      were 0.01 and 0.01 microm, respectively. Fisher's PLSD intervals at the 0.05
      level of significance for comparisons of means of gloss among five composites and
      four polishing systems were 6 and 5 GU, respectively. Color differences
      (deltaE*ab) among five composites and four polishing methods were found to range
      from 0.2 to 1.1.

PMID- 15478489
TI  - Effects of removing residual peroxide and other oxygen radicals on the shear bond
      strength and failure modes at resin-tooth interface after tooth bleaching.
AB  - PURPOSE: To investigate the effects of removing residual peroxide on the bond
      strength and the failure mode at the interface of resin-based composite and
      enamel after tooth bleaching. METHODS: Standard-sized light-cured resin cylinders
      were formed on, and bonded to the flattened bleached enamel surfaces of 60 human
      canine and premolars which had previously been subjected to three different
      surface treatments for 3 minutes: (1) catalase; (2) 70% ethanol; (3) sprayed
      water. For each experimental group (n=12), non-bleached teeth and 2-week post
      bleached teeth without any surface treatment were used for negative and positive
      control respectively. Specimens were thermocycled, tested in shear until failure,
      and the results statistically analyzed. All fractured specimens were examined by
      scanning electron microscopy. RESULTS: Pretreatment of bleached surface with the
      catalase and the ethanol prior to bonding significantly improved the composite
      enamel bond strength compared to the water-sprayed group (P< 0.05). However, the
      bond strength level of the ethanol group did not return to the level recorded for
      the non-bleached negative control group. Scanning electron microscopic
      examination of randomly selected, fractured specimens indicated that the peroxide
      induced reduction in bond strength was related to alterations in both attachment
      surface area at the resin-enamel interface and resin quality.

PMID- 15478490
TI  - Single-step, self-etch adhesives behave as permeable membranes after
      polymerization. Part I. Bond strength and morphologic evidence.
AB  - PURPOSE: To test the hypotheses that microtensile bond strengths of single-step,
      self-etch adhesives to hydrated dentin are adversely affected by delayed
      activation of a light-cured composite, as well as the use of a chemical-cured
      composite. METHODS: Seven commercially available and one experimental single
      step, self-etch adhesives were bonded to hydrated human dentin. A dual-cured
      composite was used and activated using: [1] the light-cured mode (base paste only
      control), [2] the chemical-cured mode (base and catalyst pastes, in the dark);
      and [3] delayed light-activation (base syringe only, left on top of cured
      adhesives in the dark for 20 minutes before activation). After microtensile bond
      strength evaluation, fractured samples were examined using SEM. Intact,
      unstressed interfaces of [1] and [3] were examined with TEM. Microtensile bond
      strengths were also evaluated for selected adhesives bonded to dehydrated dentin
      and coupled with the composite activated by [2] or [3]. RESULTS: For all
      adhesives, bond strengths decreased significantly to bonded hydrated dentin when
      the composites were activated with [2] or [3] (P< 0.001). Whereas the hybrid
      layer-adhesive interface was intact, water-blisters that developed along the
      adhesive-composite interface in these two modes were responsible for the decline
      in bond strength. When bonded to dehydrated dentin, delayed light-activation of
      the light-cured composite did not result in compromised bond strength. The
      results of chemical-cured composites improved but were more variable and system
      dependent.

PMID- 15478491
TI  - Effect of re-use of a disposable micro-polisher on the surface of a microhybrid
      resin composite.
AB  - PURPOSE: To evaluate the surface roughness of Esthet-X resin-based composite with
      the multi-use of a one-step disposable diamond micro polisher PoGo with
      profilometer and scanning electron microscope (SEM). METHODS: 35 discs were
      obtained by condensing Esthet-X in an 8x2 mm plexiglass mold covered with a Mylar
      strip. The specimens were polymerized 40 seconds on both sides. Five Mylar
      strips' surfaces were used as a control. Six groups of five discs were formed by
      reusing the same PoGo disc 1, 2, 3, 4, 5 and 6 times. The surfaces of the 30
      discs were ground wet with a 1200 grit silicon carbide paper and then polished 30
      seconds with PoGo. The surface roughness was measured with Surtronic 4. One
      representative sample of each group was selected to visualize the surfaces
      morphology by SEM. The results were statistically evaluated by one-way ANOVA (P<
      0.01). RESULTS: There were no statistical differences with the Mylar-created
      surfaces and one, two and three times' use of PoGo. Furthermore, reusing PoGo one
      to four times was not found to affect the surface roughness (P> 0.01). There were
      no differences with four and five re-uses of PoGo while using the same disc six
      times exhibited more roughness than single use and Mylar strip (P< 0.01). The SEM
      and the profilometer revealed similar results.

PMID- 15478492
TI  - Measuring and managing profit.
AB  - One of the main purposes of any business, including the dental practice, is to
      make a profit. The first step is to attract and maintain patients through
      excellent care and unparalleled customer service. A practice can continue to
      provide the best for patients only if it operates profitably. Understanding why
      profit counts, watching cost, and setting goals will help bring you the financial
      independence you deserve.

PMID- 15478493
TI  - Wear of aluminum oxide antagonists by commercially available composites and
      compomers.
AB  - PURPOSE: To investigate the wear of aluminum oxide antagonists by 19 light
      curing, commercially available composites and compomers. The influence of the
      filler particle size of the composites, the filler particle material and the
      filler particle morphology was determined. METHODS: Occlusal contact wear of the
      antagonists was simulated in a sliding wear test. Eight antagonists and specimens
      of each material were tested in a pin-on-block design with oscillating sliding of
      an aluminum oxide antagonist (Degussit antagonist, 5 mm diameter). After 50,000
      cycles the contact area was evaluated using a dedicated software (UTHSCA image
      tool for windows V 2.0) under a light microscope. The size of the contact area
      was measured. RESULTS: Three types of boundaries of the contact area could be
      observed: (1) Sharp boundary, (2) No sharp boundary but easy to identify, and (3)
      No sharp boundary and difficult to identify. The method of Pearson was used to
      calculate the correlation coefficients. The coefficient of determination between
      the ranking of the measured contact area and the ranking of the maximum particle
      size was r2= 0.46 (P> 0.05). Composite materials with the same particle size were
      ranked by their filler content (wt. %).

PMID- 15478494
TI  - Clinical trial evaluating the peroxide concentration response of whitening strips
      over 28 days.
AB  - PURPOSE: The research evaluated the peroxide concentration whitening response
      following self-directed use of whitening strips over a 28-day period. METHODS: A
      randomized, double-blind, parallel group clinical study was conducted. 37 healthy
      adult volunteers were randomly assigned to one of three groups based on tooth
      color at screening: 1.8% hydrogen peroxide strips (HPS), 3.3% HPS or 5.3% HPS.
      Subjects applied the assigned maxillary strips twice per day for 30 minutes over
      28 days. Tooth color was evaluated at day 7, 14 and 28 from digital images of the
      maxillary six anterior teeth using a standard method. Treatments were compared
      using analysis of covariance (adjusting for baseline) at a 0.05 level of
      significance. RESULTS: Hydrogen peroxide at concentrations ranging from 1.8-5.3%
      resulted in significant (P< 0.05) color improvement versus baseline as early as
      Day 7. There was a concentration-response for reduction in yellowness (deltab*)
      and lightness improvement (deltaL*) at all timepoints, favoring the higher
      concentrations. While the concentration-whitening relationship approached a
      linear response at Day 7, continued treatment resulted in incremental color
      improvement. All three peroxide concentrations were well tolerated, and no
      subjects discontinued early due to a treatment-related adverse event.

PMID- 15478495
TI  - Effects of bonded composites vs. amalgam on resistance to cuspal deflection for
      endodontically-treated premolar teeth.
AB  - PURPOSE: To determine, by means of a non-destructive experimental procedure, the
      extent to which tooth cusps are weakened by endodontic procedures and the
      effectiveness of adhesive bonding restoration in reducing cuspal deflection as a
      function of different restorative procedures. METHODS: A mechanically controlled
      loading device induced cuspal deflection by axial force (range 98-294 N) on an
      occlusal surface while LTS laser twin sensors registered the amount of
      deflection. Cusp deflection values, in microns, were recorded for each tooth.
      Thirty sound maxillary premolars teeth were sequentially evaluated in the
      following conditions: A) intact tooth; B) completion of endodontic and
      restorative procedures. Teeth were randomly divided into five groups and restored
      respectively with: A) amalgam (Dispersalloy); B) Spectrum TPH; C) Surefil; D)
      Esthet-X; E) Esthet-X + Dyract Flow. RESULTS: The average loading force needed to
      induce 1 microm cusp deflection was evaluated, for all groups, in intact teeth
      (range 49.52-58.76 N/microm) and in restored teeth (range 8.56 - 47.05 N/microm).
      Statistical analysis (ANOVA for repeated measures) has been performed. Mean
      structural recovery values after restorative treatment were 17% with amalgam, 60%
      with Spectrum TPH, 59% with SureFil, 54% with Esthet-X, and 99% with Esthet
      X/Dyract.

PMID- 15478496
TI  - A case-crossover analysis of fine particulate matter air pollution and out-of
      hospital sudden cardiac arrest.
AB  - Numerous recent epidemiologic studies report increases in the daily incidence of
      cardiovascular disease mortality and morbidity related to increases in daily
      levels of fine particulate matter (PM)* air pollution. This study sought to
      evaluate the possible association between the occurrence of out-of-hospital
      sudden cardiac arrest (SCA) and daily PM levels in the Seattle metropolitan area.
      The underlying hypothesis was that PM exposure may act as a cardiovascular
      trigger for SCA. A case-crossover study was conducted among 362 SCA cases
      identified by paramedics from October 1988 through June 1994. Cases were King
      County WA residents who were married, aged 25 to 74 years at the time of their
      SCA, with no prior history of clinically recognized heart disease or other life
      threatening comorbid conditions. Daily averages of regional PM monitoring data
      for nephelometry measures of PM (reported in units of bsp, referred to as
      coefficient of light scattering) and PM10 (particulate matter 10 microm or
      smaller in aerodynamic diameter) from three monitoring sites were used as
      indicators of exposure. In the case-crossover analysis, PM levels during index
      times of cases within the five days preceding an SCA were compared with PM levels
      at referent days, defined as the same days of the week during the month of SCA
      occurrence. Lag periods for index days of 0 to 5 days were investigated. The
      estimated relative risk (RR) at a lag of 1 day for an interquartile range (IQR)
      change in nephelometry (0.51 bsp) was 0.893 (95% confidence interval [CI] 0.779
      1.024). Varying the lag period had only minimal change on the observed
      association. The estimated relative risk at a lag of 1 day for an IQR change of
      PM10 (19.3 microg/m3) was 0.868 (95% CI 0.744-1.012). There was no evidence of
      confounding by ambient daily exposures to carbon monoxide or sulfur dioxide.
      Analysis of effect modification by individual-level variables, including age,
      cigarette smoke exposure, physical activity, and other risk or protective factors
      for cardiovascular disease did not reveal any susceptible subgroups. The null
      results of this study may be due to several factors; these include: the highly
      selected nature of this SCA case series; the fact that cases were free of prior
      clinically recognized heart disease or major life-threatening comorbidity; and
      the possibility that PM exposures at the relatively low levels seen in the
      Seattle metropolitan area do not trigger cardiovascular toxic mechanisms that
      culminate in SCA.

PMID- 15478497
TI  - Preparing practice for the 'white choppy water' that could lie ahead.

PMID- 15478498
TI  - Fatty liver syndrome and displaced abomasum affect dairy cows in July.

PMID- 15478499
TI  - Relationship of speed of slaughter on infected premises and intensity of culling
      of other premises to the rate of spread of the foot-and-mouth disease epidemic in
      Great Britain, 2001.
AB  - During the foot-and-mouth disease epidemic in the UK in 2001, two major control
      policies were the rapid identification of cases and the culling of animals on
      infected premises and on dangerous contact premises. Dangerous contact premises
      were divided into two groups, premises contiguous to an infected premises and non
      contiguous premises. In England, the largest numbers of geographically clustered
      infected premises were in Cumbria, the South West (Somerset, Devon and Cornwall)
      and the Settle/Clitheroe area straddling the Yorkshire-Lancashire border. In each
      of these clusters, the rate of spread of the disease, the average time from the
      first lesion to slaughter on infected premises, and the intensity of culling of
      contiguous premises and non-contiguous premises were calculated for seven-day
      periods. Linear regression analysis was used to look for relationships between
      these factors and the rate of spread of the disease. The average time from the
      first lesion to slaughter had a statistically significant relationship in two of
      the three clusters and the intensity of culling of non-contiguous premises had a
      significant relationship in one. The intensity of culling of contiguous premises
      had no significant relationship in any of the three clusters.

PMID- 15478500
TI  - Variable patterns of distribution of PrP(CWD) in the obex and cranial lymphoid
      tissues of Rocky Mountain elk (Cervus elaphus nelsoni) with subclinical chronic
      wasting disease.
AB  - Sections of medulla oblongata, taken at the level of the obex, palatine tonsil
      and medial retropharyngeal lymph node from 10,269 captive Rocky Mountain elk
      (Cervus elaphus nelsoni), were examined by immunohistochemical staining with
      monoclonal antibody for the prion protein associated with the transmissible
      spongiform encephalopathy of cervids, chronic wasting disease (PrP(CWD)). The
      protein was detected in 226 of them. On the basis of the anatomical location of
      the deposits in the brainstem of 183 elk, four distinct patterns of distribution
      of PrP(CWD) within the parasympathetic region of the dorsal motor nucleus of the
      vagus nerve and the adjacent nuclei were observed. Mild gross lesions of chronic
      wasting disease (serous atrophy of fat) were observed in only three elk, all with
      spongiform degeneration; the other elk were considered to be in the preclinical
      stage of the disease. In contrast with the relatively predictable distribution of
      prion protein (PrP) in the brain and cranial nodes of sheep and mule deer, the
      distribution of PrP(CWD) in the brain and nodes of the elk was more variable and
      unrelated to their PrP genotype. One hundred and fifty-five of the 226 positive
      elk had deposits of PrP(CWD) in the brainstem and lymphoid tissues, 43 had
      deposits only in the lymphoid tissue and 28 had deposits only in the brainstem.

PMID- 15478502
TI  - Enterovirus encephalomyelitis in pigs in Japan caused by porcine teschovirus.

PMID- 15478501
TI  - Rabies diagnosis in the presence of strychnine and carbamate.

PMID- 15478503
TI  - Pathology and experimental prophylaxis of avian poxvirus in red-legged partridges
      (Alectoris rufa).

PMID- 15478504
TI  - Resistance in cattle worms.

PMID- 15478505
TI  - Docking dogs' tails.

PMID- 15478506
TI  - Tartar source.

PMID- 15478507
TI  - Tartar source.

PMID- 15478508
TI  - How different are internists and FPs?

PMID- 15478509
TI  - Money and status.

PMID- 15478510
TI  - Just what is a family physician, anyway?

PMID- 15478512
TI  - Big ideas to help your practice thrive.

PMID- 15478511
TI  - ICD-9 changes: update now or pay later.

PMID- 15478513
TI  - Group visits hit the road.

PMID- 15478514
TI  - Making time to listen.

PMID- 15478516
TI  - Starting the doctor-patient relationship on the right foot.

PMID- 15478515
TI  - "Insuring" the uninsured.

PMID- 15478517
TI  - Writing off patient balances.

PMID- 15478518
TI  - Billing for precepting.

PMID- 15478519
TI  - Making a living and a life.

PMID- 15478520
TI  - Risk factors for osteoporosis at the knee in the spinal cord injury population.
AB  - BACKGROUND: The objective of this study was to determine modifiable and
      nonmodifiable risk factors for bone loss at the knee in individuals with spinal
      cord injury (SCI) by examining known risk factors for osteoporosis in the general
      population and additional, unique nonmodifiable SCI elements including age at
      injury onset, injury duration, and extent of neurologic injury (level and
      completeness). METHODS: Risk factors were examined by logistic regression in 152
      individuals with chronic SCI. Knees were classified as osteoporotic based on
      whether bone mineral density (BMD) of the knee as assessed by dual-energy x-ray
      absorptiometry fell within the 95% confidence interval of the BMD of the knee of
      individuals who had experienced fractures at the knee. RESULTS: Accuracy for
      predicted membership in the osteoporotic group and nonosteoporotic group were
      79.22% and 69.33%, respectively. Of all variables included in the analysis, 3 had
      a significant effect on predicted group membership: completeness of injury (P <
      0.0001), body mass index (BMI) (P = 0.0035), and age (P = 0.0394). Individuals
      with complete injuries were 6.17 times (617%) more likely to have BMD of the knee
      low enough to place them in the osteoporotic category. The odds ratio for BMI
      indicated that every unit increase in BMI lowered the odds of being in the
      osteoporotic group by 11.29%. The odds ratio for age indicated that every 1-year
      increase in age increased the odds of being in the osteoporotic group by 3.54%.
      No other modifiable or nonmodifiable risk factors were significant predictors.
      CONCLUSION: Completeness of injury dictates and overrides most modifiable and
      nonmodifiable risk factors for bone loss at the knee leading to pathologic
      fractures in SCI. SCI osteoporosis may be classified more appropriately as
      neurogenic in origin.

PMID- 15478521
TI  - Bone loss at the os calcis compared with bone loss at the knee in individuals
      with spinal cord injury.
AB  - BACKGROUND/OBJECTIVE: The objective of this study was to document acute bone loss
      at the os calcis and compare it with bone loss at the knee following spinal cord
      injury (SCI) as a potential proxy for bone loss in individuals with SCI. METHODS:
      Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry
      (DEXA) at the knee and os calcis, which also was assessed by ultrasound in 6
      individuals--5 with complete SCI and 1 with incomplete SCI--at means of 33.5 and
      523 days following injury. RESULTS: Bone mineral was progressively greater as
      measured from proximal to distal sites. The net average BMD of the knee declined
      24% (P = 0.017). The distal femur lost 27% (P = 0.038) and the proximal tibia
      lost 32% (P = 0.015), whereas the os calcis lost 38% (P = 0.001) as measured by
      DEXA and 49% (P < 0.001) as estimated from ultrasound. The mean loss of 24% at
      the knee was significantly different from the loss percentages at the os calcis
      as measured by both techniques: DEXA (P = 0.036) and ultrasound (P = 0.043).
      Differences between annualized loss rates at the knee and the os calcis measured
      by both techniques also were significant: DEXA (P = 0.032) vs ultrasound (P =
      0.038). However, annualized loss rates demonstrated the same trend for
      differential loss at the sites examined in the 5 individuals with complete
      injuries but not for the 1 participant with an incomplete injury. The loss rates
      were similar for the complete and incomplete participants at the os calcis, but
      not at the knee. CONCLUSION: The BMD of the os calcis declined 38% by DEXA and
      49% by ultrasound compared with 24% at the knee when measured 1 to 1.5 years
      after injury. BMD of the os calcis and distal femur measured by DEXA in persons
      with complete SCI were highly correlated (r = 0.84, P < 0.0001).

PMID- 15478522
TI  - Risk factors for osteoporosis in persons with spinal cord injury: what we should
      know and what we should be doing.

PMID- 15478523
TI  - Efficacy and safety of tolterodine in people with neurogenic detrusor
      overactivity.
AB  - OBJECTIVE: To compare tolterodine with oxybutynin and placebo in people with
      neurogenic detrusor overactivity. DESIGN: Prospective, randomized, double-blind,
      crossover trial plus open-label comparative stage. PARTICIPANTS: Ten participants
      with neurogenic detrusor overactivity due to spinal cord injury or multiple
      sclerosis who used intermittent catheterization. METHODS: Bladder capacity on
      cystometrogram, a 10-day record of catheterization volumes, number of incontinent
      episodes per day, and perceived dry mouth using a visual analog scale (VAS) were
      measured for the following: (a) a blinded comparison: tolterodine, 2 mg twice
      daily, vs placebo, twice daily; and (b) an unblinded comparison: oxybutynin vs
      tolterodine, each at self-selected doses (SSDs). RESULTS: Tolterodine, 2 mg twice
      daily, was superior to placebo in enhancing catheterization volumes (P < 0.0005)
      and reducing incontinence (P < 0.001), but was comparable with placebo in
      cystometric bladder capacity. Efficacy of tolterodine SSD was comparable with
      oxybutynin SSD with regard to catheterization volumes, degree of incontinence,
      and cystometric bladder capacity. The side effect profile (dry mouth) was
      comparable between tolterodine, 2 mg twice daily, and placebo, but differed
      significantly when comparing tolterodine SSD with oxybutynin SSD (P < 0.05).
      CONCLUSION: Tolterodine, when used at SSDs, is comparable with oxybutynin at SSDs
      in enhancing bladder volume and improving continence, but with less dry mouth.
      Tolterodine at the recommended dosage of 2 mg twice daily improves incontinence
      and bladder volumes compared with placebo, and without significant dry mouth.
      Larger doses of tolterodine may be needed to achieve best effect in this
      population, but further studies are required.

PMID- 15478524
TI  - Double-blinded, placebo-controlled trial of midodrine for exercise performance
      enhancement in tetraplegia: a pilot study.
AB  - BACKGROUND/OBJECTIVE: Spinal cord injury (SCI) impairs cardiovascular autonomic
      responses to exercise and, depending on the level of injury, may result in
      hypotension and pathologic fatigue with exertion. Other clinical populations with
      sympathetic regulatory dysfunction, but without skeletal muscle paralysis,
      exhibit similar signs and symptoms. Their ability to engage in physical activity
      improves with elevation of blood pressure through pharmacologic treatment:
      Midodrine, an oral alpha-sympathomimetic agent, has been shown to be safe and
      efficacious for this purpose. Use of this medication in individuals with SCI
      merits investigation. METHODS: Double-blind, placebo-controlled, randomized,
      crossover, within-subjects protocol. Four participants with chronic, motor
      complete injuries from C6 to C8 underwent 4 peak exercise tests (PXT) using a
      wheelchair ergometer, following administration of midodrine, 5 mg, 10 mg, and
      placebo, in random order. Heart rate, blood pressure, oxygen consumption (VO2),
      and perceived exertion were measured. RESULTS: Treatment with midodrine, 10 mg,
      was associated with elevated systolic blood pressure during peak exercise in 3
      participants. Two participants showed a concurrent decrease in perceived exertion
      and increase in VO2. No adverse effects of midodrine were evident. CONCLUSION:
      Midodrine enhances exercise performance in some individuals with SCI, similar to
      other clinical populations with cardiovascular autonomic dysfunction.

PMID- 15478525
TI  - Development of a new assessment of effort and assistance in standing pivot
      transfers with functional electrical stimulation.
AB  - BACKGROUND: Currently available clinical tools for assessing rehabilitation
      outcomes do not capture both the effort exerted and assistance required for
      persons with spinal cord injuries to perform a standing pivot transfer using
      functional electrical stimulation (FES). This study was undertaken to develop and
      apply a clinical tool to measure the ability to stand and transfer with
      electrical stimulation. METHODS: The Functional Performance Measure (FPM)
      methodology was chosen to develop a tool to measure performance. Through an
      iterative review of videotaped FES transfers, fundamental components of the
      standing pivot transfer were identified and standardized performance criteria for
      user effort and helper assistance were developed for every phase using the 8
      point FPM scales. RESULTS: Interrater and intrarater reliability were established
      with a simple kappa coefficient for the effort scale and assistance scale. The
      final version of the tool has been applied to users of the implanted FES standing
      neuroprosthesis to describe the effort and assistance required for the transfer.
      CONCLUSION: The tool has been shown to capture the effort and assistance needed
      during FES-assisted standing pivot transfers throughout all phases of the
      transfer.

PMID- 15478526
TI  - Daily vs twice daily enoxaparin in the prevention of venous thromboembolic
      disorders during rehabilitation following acute spinal cord injury.
AB  - BACKGROUND: Subcutaneous administration of low molecular weight heparin (eg,
      enoxaparin) has been shown to be safe and effective in the prevention of acute
      venous thromboembolic (TE) disease following acute spinal cord injury (SCI) in
      the rehabilitation setting. However, emerging evidence suggests that different
      dosing strategies may be equivalent. OBJECTIVE: To determine whether subcutaneous
      enoxaparin, 40 mg once daily, when compared with subcutaneous enoxaparin, 30 mg
      twice daily, is equally safe and effective in the prevention of venous TE disease
      in patients with SCI. DESIGN: Retrospective chart review. SETTING: A
      freestanding, inpatient, acute, rehabilitation hospital. PATIENTS: One hundred
      and twenty-nine patients admitted from June 2000 through June 2002 for inpatient
      rehabilitation following an acute SCI who received either enoxaparin, 40 mg once
      daily, or enoxaparin, 30 mg twice daily, for prophylaxis for TE disease. RESULTS:
      Equivalent prophylaxis efficacy was seen in both enoxaparin groups. Symptomatic
      venous thromboembolism did not differ, with deep vein thromboses occurring in 1
      of 49 (2.0%) patients receiving twice-daily enoxaparin, and 1 of 80 (1.25%)
      patients receiving once-daily enoxaparin (chi2 = 0.125, NS). Pulmonary embolism
      was seen in 1 of 49 (2.0%) patients treated with twice-daily enoxaparin and in
      none of the patients in the once-daily group (chi2 = 1.64, NS). Bleeding
      complications also did not differ between the 2 treatment groups; these were
      observed in 2 of 49 (4.1%) patients receiving twice-daily enoxaparin and in 5 of
      80 (6.3%) patients receiving once-daily enoxaparin (chi2 = 0.228, NS).
      CONCLUSION: Subcutaneous enoxaparin administered once or twice daily is equally
      effective for the prevention of venous TE disease. Both dosing strategies are
      associated with a low incidence of bleeding in patients with SCI who are
      undergoing rehabilitation.

PMID- 15478527
TI  - Perceived quality of care and outcomes following spinal cord injury: minority
      status in the context of multiple predictors.
AB  - OBJECTIVE: To determine whether patients with spinal cord injury (SCI) who are
      members of minority groups experience a disadvantage with regard to quality of
      care, and investigate predictors of perceived quality of care and indicators of
      outcome. DESIGN: Correlational analysis of longitudinal data. SAMPLE: One hundred
      and forty-three individuals with SCI in the first year following injury (43.3%
      tetraplegia, 56.7% paraplegia; 53.6% of total had complete injuries). SETTING:
      Hospital and postdischarge (usually outpatient) care at 3 SCI model systems. MAIN
      OUTCOME MEASURES: Perceived quality of acute, rehabilitative, and continuing care
      rated by patients according to standard format. Objective indicators of amount of
      care (eg, length of stay [LOS], charges) and outcomes (eg, medical complications,
      Functional Independence Measure [FIM] scores, a life satisfaction measure [the
      Diener Scale], and the Craig Handicap and Reporting Technique [CHART; a community
      participation scale]). RESULTS: Minorities did not report statistically
      significant differences in perceived quality of care or other indicators (eg,
      amount of care, medical complications, FIM gain, life satisfaction, and CHART
      scores) compared with other groups. Severity of injury affected LOS and activity
      outcomes. Satisfaction with medical care before the injury significantly
      predicted perceived quality of acute hospital care, inpatient rehabilitation, and
      continuing care (P < 0.03, 0.02, and 0.02, respectively). CONCLUSION: A number of
      factors may affect variations in perceived quality of care and outcomes, but
      ethnicity is not always the most important predictor. Asking patients about their
      satisfaction with previous care can assist in distinguishing satisfaction with
      current care from pre-existing biases.

PMID- 15478528
TI  - Factors influencing bladder stone formation in patients with spinal cord injury.
AB  - OBJECTIVE: Bladder stones that form in patients with spinal cord injury (SCI) can
      cause significant morbidity. This study sought to analyze factors associated with
      bladder stone formation to determine which patients might be at increased risk to
      develop bladder stones. METHODS: A review of 56 SCI patients treated for bladder
      calculi over a 10-year period at a single institution was performed. These
      patients were compared with a control population of general SCI patients known to
      be stone free. The factors compared were patient age, duration of injury, level
      of injury, completeness of injury, method of bladder management, and the presence
      of documented urinary tract infections with urease-producing organisms. RESULTS:
      All patients with stones were male and had a median age of 58.5 years. The median
      level of injury was C6, the median time since injury was 21 years, 66% had
      complete injuries, 68% managed their bladders with indwelling catheters or
      suprapubic tubes, and 83% had a history of infections with urease-producing
      organisms. When compared with the control group, patients forming bladder stones
      were older (P = 0.03), were more likely to have indwelling catheters (P <
      0.0001), had a history of infections with urease-producing organisms (P = 0.04),
      and had complete injuries (P = 0.018). CONCLUSION: This information can be used
      to identify patients who have an increased risk of bladder stones and measures
      can be taken to reduce their incidence and morbidity.

PMID- 15478529
TI  - Arterial stiffness in persons with paraplegia.
AB  - BACKGROUND: Arterial stiffness recently has been identified as an independent
      risk factor for cardiovascular disease. An accurate and noninvasive estimate of
      arterial stiffness can be made through close examination of the pulse wave
      contour, and is expressed as the augmentation index (AI). Increased stiffness is
      associated with increased systolic blood pressure (SBP), pulse pressure, and
      reduced baroreceptor sensitivity. The purpose of this study was to compare the
      common carotid AI in participants with paraplegia vs able-bodied controls as well
      as compare group differences for blood pressure while supine and in response to
      gravitational stress. PARTICIPANTS: Study participants were 19 healthy
      individuals with paraplegia (below T6) and 9 able-bodied controls matched for
      age, height, and weight. METHODS: An electronic tilt table was used for testing
      responses to gravitational stress at 4 angles (-10 degrees, 10 degrees, 35
      degrees, and 75 degrees). AI was assessed at each angle of tilt using an
      externally applied high-fidelity strain-gauge transducer placed over the right
      common carotid artery. RESULTS: AI was augmented in the group with paraplegia
      compared with the able-bodied group (8.0 +/- 3.9 vs 6.7 +/- 2.8, respectively; P
      < 0.05). Supine blood pressure and the SBP response to tilt did not differ
      between the groups, and there were no tilt-angle effects on SBP. CONCLUSION: In
      normotensive persons with paraplegia, AI was increased significantly compared
      with matched able-bodied controls, which may suggest the premature development of
      arterial disease in this population.

PMID- 15478530
TI  - A follow-up program in India for patients with spinal cord injury: paraplegia
      safari.
AB  - BACKGROUND: Once patients with spinal cord injury (SCI) were discharged from the
      hospital, it was very difficult for them to return for follow-up, particularly
      during the first year, due to problems regarding finances and social issues, as
      well as extreme physical barriers. Because of these barriers, a large number of
      patients were presenting for re-admission for reasons that might have been
      prevented if they had come for routine follow-up. Therefore, it was felt that an
      attempt to visit the patient's residence to conduct a follow-up would be of great
      help. OBJECTIVES: To evaluate and improve the status of rehabilitation of
      community-dwelling SCI patients in their homes and attempt to decrease the rate
      of re-admissions. MATERIAL AND METHODS: In this program, the home visit team
      consisted of an orthopedic surgeon, physiotherapist, occupational therapist,
      prosthetist and orthotist engineer, medical social worker, and a nurse.
      Rehabilitated discharged patients received needed medical treatment, orthotics,
      and vocational guidance at their residences. Patients who required re-admission
      were assisted back to the hospital. CONCLUSION: The home visit program decreased
      the number of re-admissions by improving the status of rehabilitation, which
      raised the quality of care for patients with SCI.

PMID- 15478531
TI  - Urolithiasis associated with indinavir in a patient with spinal cord injury.
AB  - OBJECTIVE: To report a case of indinavir-induced urolithiasis, and the greater
      risk of this occurrence in individuals with spinal cord injury (SCI) who require
      fluid restriction for an intermittent catheterization program (ICP). METHODS:
      Case report. RESULTS: A 38-year-old man with a T4 ASIA A SCI (according to the
      American Spinal Injury Association classification scale) and human
      immunodeficiency virus (HIV) infection was using an ICP and taking indinavir (a
      protease inhibitor) as part of his antiviral regimen. Cystoscopy was performed to
      rule out recurrent urethral condylomata. He was found to have a bladder stone
      measuring 0.5 cm x 0.5 cm x 0.3 cm, which, on analysis, was composed of indinavir
      (100% exterior, 90% interior). The bladder stone was removed under direct
      visualization. The plain abdominal radiograph did not reveal any stones.
      CONCLUSION: Indinavir is a frequently used drug for the treatment of HIV that has
      the potential to induce urinary lithiasis. This is particularly problematic for
      individuals with SCI who are on fluid restriction and an ICP. Therefore,
      cystoscopy and monitoring for indinavir-induced urolithiasis should be undertaken
      in individuals with SCI who are taking indinavir. Considerations include
      switching to a different protease inhibitor or choosing an entirely new HIV drug
      cocktail with less potential for urolithiasis.

PMID- 15478532
TI  - Fulminant Clostridium difficile colitis in a patient with spinal cord injury:
      case report.
AB  - BACKGROUND: In certain patients with Clostridium difficile colitis (CDC), a life
      threatening systemic toxicity may develop despite appropriate and timely medical
      therapy. DESIGN: Literature search and case report. FINDINGS: A 39-year-old man
      with T10 paraplegia presented with a distended, quiet abdomen following recent
      treatment with antibiotics for pneumonia. Diarrhea was not present. Complete
      blood counts demonstrated a marked leukocytosis. A CT scan of the abdomen
      demonstrated a state of diffuse pancolonic inflammation with peritoneal fluid.
      The patient was taken to the operating room and underwent total abdominal
      colectomy with oversewing of the rectal stump and end ileostomy for treatment of
      the fulminant CDC. CONCLUSION: Patients with spinal cord injury (SCI) often
      receive antibiotics for infections of the aerodigestive tree and urinary tract
      and for problems with skin integrity. A heightened awareness of the development
      of fulminant CDC remains essential in the care of patients with SCI. Any
      unexplained abdominal illness after recent antibiotic administration should alert
      the physician to CDC and its potential as a fulminant, potentially fatal illness.

PMID- 15478534
TI  - The morality of medicine.

PMID- 15478533
TI  - Bilateral locked facets of the lumbosacral spine: treatment with open reduction
      and transpedicular fixation.
AB  - BACKGROUND: A 23-year-old man was involved in a motor vehicle crash and found to
      have bilateral locked facets at L5-S1. His neurologic examination, radiographic
      workup, surgical management, postoperative care, and the relevant literature are
      discussed. DESIGN: Case report and literature review. RESULTS: This patient
      underwent solid fusion with anatomic alignment following open reduction and
      internal fixation. He made a good neurologic recovery. CONCLUSION: Early surgery,
      consisting of open reduction, fixation, and fusion, provides the best results in
      patients with lumbosacral fracture-dislocations.

PMID- 15478535
TI  - Biomedical coatings to improve the tissue-biomaterial interface.
AB  - One of the most important factors determining the degree of tissue interaction of
      an implanted device is the property of its surface. Thus, great importance is
      given to chemical and morphological characteristics of biomaterial surfaces to
      improve biocompatibility, cell migration, proliferation and differentiation,
      mechanical stability and endogenous tissue ingrowth. In order to obtain new and
      healing stimulating properties, it is possible to apply a coating or more
      generally a surface treatment to the surface of a prosthetic device. One of the
      most versatile methods for coating is thermal spray technology. This paper
      considers the principle of thermal spray processes and their application in the
      biomedical field, namely the coatings used for orthopedic prostheses and dental
      implants. Among thermal spray processes, plasma spray as well as High Velocity
      Oxygen Fuel (HVOF) processes will be particularly considered and their most
      important aspects will be illustrated.

PMID- 15478536
TI  - In vitro models to test orthopedic biomaterials in view of their clinical
      application in osteoporotic bone.
AB  - The development of in vitro cell cultures, in association with in vivo
      experimentation, greatly improved the characterization of biomaterials for
      orthopedic devices before their clinical use. In recent years an increasing
      interest has arisen in the use of both pathological osteoblast cultures and
      animal models to perform in vitro and in vivo tests on biomaterial behavior. A
      growing number of prostheses, in fact, are implanted in osteoporotic patients,
      due to the increasing age of the population. Moreover, the presence of
      osteoporosis may affect bone-biomaterial osteointegration in these patients. The
      present paper is a literature review and, after a short description of in vitro
      studies for characterization of osteoblasts derived from osteoporotic bone, the
      results of in vitro studies on biomaterial biocompatibility and osteointegration
      rate in the presence of osteoporotic bone derived osteoblast cultures are
      reported. Pathological cell culture models are able to demonstrate the different
      behavior of osteoblasts in response to biomaterials, when comparing normal and
      pathological conditions.

PMID- 15478537
TI  - A biomimetic gelatin-calcium phosphate bone cement.
AB  - The interest in new bone substitutes is rapidly increasing in the field of
      orthopedic surgery. A variety of calcium phosphate bone cement has been developed
      and different additives have been used to improve their biocompatibility and
      bioactivity. Following a biomimetic strategy aimed at reproducing bone
      characteristics, this study investigates the biological properties of a new
      gelatin enriched calcium phosphate cement (GEL-CP) that exhibits improved
      mechanical properties with respect to cement prepared without gelatin (C-CP).
      Human osteoblast MG63 were cultured on the surfaces of GEL-CP and were compared
      to cells cultured on C-CP samples, and on polystyrene of plate culture as control
      (C). Cell attachment, proliferation and differentiation were evaluated up to 21
      days. SEM revealed that osteoblasts grown on GEL-CP showed a normal morphology
      and biological tests demonstrated very good rate of proliferation and viability
      in every experimental time. The presence of gelatin stimulated alkaline
      phosphatase activity, collagen and transforming growth factor 31 production. The
      data indicate that the new cement GEL-CP favors osteoblast proliferation,
      activation of their metabolism and differentiation. The remarkable improvement of
      the setting properties of the calcium phosphate cement due to the presence of
      gelatin suggest that the biomimetic composite material could be successfully
      applied as bone substitute.

PMID- 15478538
TI  - Poly(2-hydroxyethyl methacrylate) biomimetic coating to improve osseointegration
      of a PMMA/HA/glass composite implant: in vivo mechanical and histomorphometric
      assessments.
AB  - Bone implants must simultaneously satisfy many requirements, even though the
      surface properties remain a crucial aspect in osseointegration success. Since a
      single material with a uniform structure cannot satisfy all of these
      requirements, composite materials specifically designed for orthopedic or dental
      implant application should be envisaged. Two
      poly(methylmethacrylate)/hydroxyapatite composites reinforced by E-glass fibres,
      uncoated (PMMA/HA/Glass) and poly(2-hydroxyethyl methacrylate)
      (PMMA/HA/Glass+pHEMA) coated by the biomimetic method, were mechanically (push
      out test) and histomorphometrically (Affinity Index, AI) investigated in an in
      vivo rabbit model. Cylindrical implants (diameter 2 mm x 5 mm length) were
      inserted into rabbit femoral cortical (mid-diaphysis) and cancellous (distal
      epiphysis) bone, under general anesthesia. The highest values of push-out force
      and ultimate shear strength were observed for the PMMA/HA/Glass at 12 weeks,
      which significantly (p < 0.001) differed from those of PMMA/HA/Glass+pHEMA at the
      same experimental time and from those of PMMA/HA/Glass at 4 weeks. At both
      experimental times, significantly (p < 0.0005) lower values of AI were observed
      in the PMMA/HA/Glass+pHEMA versus PMMA/HA/Glass (distal femoral epiphysis: 4
      weeks = 33%; 12 weeks = 19%; femoral diaphysis: 4 weeks = 15%; 12 weeks = 11%).
      The good mechanical and histomorphometric results obtained with PMMA/HA/Glass
      should be followed by further evaluation of bone remodeling processes and
      mechanical strength around loaded PMMA/HA/Glass implants at longer experimental
      times. Finally, the biomimetic method applied to pHEMA needs to be further
      investigated in order to improve the positive effect of SBF on pHEMA and to
      enhance the coating adhesion.

PMID- 15478539
TI  - Current trends in the enhancement of biomaterial osteointegration: biophysical
      stimulation.
AB  - To enhance bone implant osteointegration, many strategies for improving
      biomaterial properties have been developed which include optimization of implant
      material, implant design, surface morphology and osteogenetic coatings. Other
      methods that have been attempted to enhance endogenous bone healing around
      biomaterials are different forms of biophysical stimulations such as pulsed
      electromagnetic fields (PEMFs) and low intensity pulsed ultrasounds (LIPUS),
      which were initially developed to accelerate fracture healing. To aid in the use
      of adjuvant biophysical therapies in the management of bone-implant
      osteointegration, the present authors reviewed experimental and clinical studies
      published in the literature over the last 20 years on the combined use of
      biomaterials and PEMFs or LIPUS, and summarized the methodology, and the possible
      mechanism of action and effectiveness of the different biophysical stimulations
      for the enhancement of bone healing processes around bone implanted biomaterials.

PMID- 15478540
TI  - In vitro and in vivo hemocompatibility evaluation of graphite coated polyester
      vascular grafts.
AB  - Attempts have been made in this study to prepare a homogeneous and stable coating
      of graphite on polyester vascular grafts (GPVG) using an electrophoresis method
      to evaluate thromboresistant and blood compatibility of GPVG in comparison to non
      coated PVG and InterGard (collagen sealed PVG) as control. Lactate dehydrogenase
      (LDH) activity measurement was carried out on all PVG types to evaluate platelet
      adhesion. To examine tissue reaction GPVG and non-coated sheets of knitted
      polyester fabric were implanted simultaneously in the dorsal flank of rats
      subcutaneously. The GPVG, non-coated and control were implanted in descending
      aorta as end-to-end or end-to-side implantation substitution in 25 sheep for 4-60
      weeks. Results showed that the graphite coating on polyester vascular grafts
      reduced the number of adherent platelets and prevent platelet activation and
      spreading on the surface in comparison with non-coated and control. Pathological
      investigation showed inflammatory reactions were totally resolved after 12 weeks
      and there was no difference in the tissue reaction between graphite coated, non
      coated and control patches. All grafts remained patent and there was no
      significant difference in patency rate between these three types of PVG. We found
      that GPVG has no need for pre-clotting and it showed lower platelet aggregation,
      thinner capsule formation and lower calcification after 15 months. However,
      suturing of GPVG was more difficult in comparison with the other types.

PMID- 15478541
TI  - Mathematical model of platelet deposition under flow conditions.
AB  - Platelet deposition in resting blood is well researched and understood. However,
      the influence of hemodynamic parameters such as wall shear rate is less clear.
      Clinical experience and experiments show an interaction between flow and platelet
      deposition. But a complete understanding of the flow influence and hence a
      quantification has not yet been achieved. A well defined experiment of flow
      dependant platelet depositions is the stagnation point flow. This kind of flow is
      ubiquitous in the circulatory system, to be found in every bifurcation and
      recirculation region. These are the areas where thrombus formations are likely to
      occur if other conditions are also met. First, experiments were performed in a
      stagnation point flow chamber. A simplified blood model, platelet rich plasma,
      was used as a test fluid. With a microscope the platelet deposition was observed
      and recorded. Platelets deposit in a characteristic pattern showing the influence
      of the flow. An analysis of this pattern is the objective of this study and is
      achieved with the help of a numerical model, which is based on a convective
      diffusive transport. The model results in a platelet deposition pattern, which in
      its shape and temporal development is very similar to experimental results. Hence
      it is concluded that the assumed transport processes are causal for platelet
      depositions and thrombus formation.

PMID- 15478542
TI  - Evaluation of adaptive support ventilation in paralysed patients and in a
      physical lung model.
AB  - OBJECTIVE: Evaluation of the respiratory pattern selected by the Adaptive Support
      Ventilation (ASV) in ventilated patients with acute, chronic respiratory failure
      and normal lungs and in a physical lung model. DESIGN: We tested ASV both on
      patients and in a physical lung model, with a normal level of minute ventilation
      and with minute ventilation increased by 30%. In each patient, respiratory
      pattern, mechanics and blood gases were recorded. SETTING: General ICU of a
      University Hospital. RESULTS: In patients with normal lungs, mean values+/-SD
      were: tidal volume (Vt) 558.1+/-142.4 mL, respiratory rate (RR) 12.6+/-1.3b/min
      and inspiratory time/total time ratio (Ti/Ttot) 42.4+/-4.1%; in COPD, mean
      values+/-SD were: Vt 724+/-171 mL, RR 9.2+/-2.7b/min and Ti/Ttot 26.6+/-10.5%; in
      restrictive ones, mean values+/-SD were: Vt 550.2+/-77.0 mL, RR 15.8+/-2.6b/min,
      Ti/Ttot 47.5+/-2.5%. In the lung model, at a normal setting, mean values+/-SD
      were: Vt 523+/-18.5 mL, RR 14+/-0.0b/min, Ti/Ttot 44.0%, in COPD, mean values+/
      SD were: Vt 678+/-0.0 mL, RR 9+/-0.0b/min, Ti/Ttot 20+/-0.7%, in restrictive one,
      mean values+/-SD were: Vt 513+/-12.8 mL, RR 15+/-0.0b/min, Ti/Ttot 48+/-1.5%. In
      model hyperventilation conditions in a normal setting a Vt of 582+/-16.6 mL, RR
      16+/-0.0b/min, Ti/Ttot 48+/-0.0% were selected, in the obstructive setting Vt
      883+/-0.0 mL, RR 9+/-0.0b/min, Ti/Ttot 20+/-0.0% and in a restrictive one Vt
      545+/-8.4 mL, RR 18+/-0.0b/min, Ti/Ttot 50-0.0%. CONCLUSIONS: In normal patients
      ASV selected a ventilatory pattern close to the physiological one, in COPD almost
      a high expiratory time pattern and in restrictive ones a reduced tidal volume
      pattern. In the model the selection was similar. In the hyperventilation test,
      ASV chose a balanced increase in both Vt and RR.

PMID- 15478543
TI  - Bilirubin-adsorption in 23 critically ill patients with liver failure.
AB  - PURPOSE: Previous studies suggest that high levels of bilirubin exert cytotoxic,
      neurotoxic and encephalopathic effects that themselves may lead to further
      deterioration of liver function and multiorgan failure. Although extracorporeal
      BA is not a causal therapy, there are case reports of clinical benefits of BA.
      The present retrospective study investigated the clinical utility and
      effectiveness of BA in 23 patients with liver failure. METHODS: Twenty-three
      patients (61+/-11 years) with excessive hyperbilirubinemia (>25 mg/dL) after
      liver transplantation (n=7), partial liver resection (n=12) and others (n=4) were
      treated with BA (3.6 liters plasma per BA, BR350, Asahi) and followed for 45+/-8
      days. RESULTS: A mean of 6.6 treatments (3-16) were performed per patient. On
      average, a single BA treatment reduced bilirubin-levels from 31+/-12 to 23.7+/-9
      mg/dL (p<0.001). Levels of bile acid were reduced from 41.8+/-6 to 33.5+/-5
      mg/dL. The 30-day mortality was 50%. BA was able to halt and stabilize the
      progressive increase in bilirubin levels in all patients. In contrast to
      survivors, non-survivors were characterized by a repeated rapid rise in bilirubin
      levels after cessation of BA treatment. CONCLUSIONS: BA is able to stabilize or
      decrease bilirubin levels in patients with liver failure. Our experience suggests
      that BA is a safe and promising short-term treatment option for patients with
      acute deterioration of hepatic function.

PMID- 15478545
TI  - Acrylamide--no evidence for accumulation in end-stage renal disease patients
      using its hemoglobin adduct as biomarker.

PMID- 15478544
TI  - The role of improved water quality on inflammatory markers in patients undergoing
      regular dialysis.
AB  - Hemodialysis utilizes large quantities of water for the preparation of dialysis
      fluid. Such water meets national standards and international standards but a
      considerable disparity exists between such standards with respect to
      microbiological purity. This study collated and retrospectively analyzed the
      impact of upgrading water systems from that specified in the US standards to
      those specified in European standards on clinical measures associated with
      inflammation in four metropolitan dialysis units for two periods. Two periods
      were compared, three months prior to and six months post upgrading the water
      treatment systems. The monthly total erythropoietin dosage and intravenous iron
      supplementation for each patient were also compared over these periods. Variables
      with significant pre-post differences were assessed using multivariate models to
      control for confounding factors. The results indicated significant increases in
      hemoglobin, ferritin and TSat (all p < 0.0001) and albumin (p = 0.0001) were
      associated with improvement in water quality. Decreases in CRP and creatinine
      (both p < 0.0001) were also noted. These findings suggest that the current
      regulations in the United States set the microbiological limits of water and
      dialysis fluid inappropriately high, and the limits should be revised downwards,
      since such an approach is reflected in improvement in markers of inflammation.

PMID- 15478546
TI  - Ozone therapy seems to be safe, but is it really clinically effective?

PMID- 15478547
TI  - [Main results and prospects of the activities of a WHO collaborating tuberculosis
      combating center in the Russian Federation].

PMID- 15478548
TI  - [To the optimization and evidence of current chemotherapy regimens for pulmonary
      tuberculosis].

PMID- 15478549
TI  - [Proteins, transporters of the body's somatic cells, and their action of the
      efficiency of chemotherapy for tuberculosis].

PMID- 15478550
TI  - [Impact of introduction of the WHO tuberculosis-controlling recommendations
      adapted to the Russian conditions on the Russian statistical tuberculosis data].
AB  - The authors share their experience in introducing the WHO tuberculosis
      controlling recommendations adapted to the Russian conditions into the Republic
      of Mariy El, in the Ivanovo, Oryol, and Tomsk Regions. All the areas are marked
      by high rates of diagnosis of MBT in the clinical diagnostic laboratories of the
      general medical network, by the increased rates of detection of patients of
      tuberculosis who isolate Mycobacterium tuberculosis, by the enhanced efficiency
      of treatment of patients with tuberculosis, as shown by the Russian statistical
      data, by the lower rates of growth of the contingents of patients with
      tuberculosis or by their reduction.

PMID- 15478551
TI  - [A programme for detection and treatment of patients with tuberculosis in the
      Saratov Region].

PMID- 15478552
TI  - [Implementation of a programme for detection and treatment of patients with
      tuberculosis in the Vladimir Region].

PMID- 15478553
TI  - [Effectiveness of artificial pneumothorax in the treatment of patients with
      pulmonary tuberculosis with multiple drug-resistant Mycobacteria].
AB  - The efficiency of treatment was compared in 2 groups of patients with destructive
      pulmonary tuberculosis and isolation of multidrug resistant Mycobacteria. In 43
      patients of a study group, artificial pneumothorax (AP) was used during
      chemotherapy with reserve drugs while 43 patients of a control group received
      chemotherapy alone. AP was shown to be highly effective in treating patients with
      destructive pulmonary tuberculosis who isolated multidrug resistant Mycobacteria.
      Moreover, by the end of 12-month therapy, AP in combination with chemotherapy
      ensured cessation of bacterial isolation in 88.7% and cavernous closure in the
      lung in 86.8%, which was almost twice higher than that with therapy with reserve
      antituberculous drugs.

PMID- 15478554
TI  - [Efficacy of chemotherapy for tuberculosis in patients who isolate drug-resistant
      strains of M. tuberculosis with different genotypes].
AB  - Two hundred and twenty-four patients with pulmonary tuberculosis and bacterial
      isolation were examined to study the efficiency of chemotherapy in patients who
      isolated drug-resistant strains of Mycobacterium tuberculosis (MBT) of different
      genotypes. According to the pattern of susceptibility to antituberculous drugs
      (ATDs), the patients were divided into 3 groups: 1) those who were found to have
      ATD-susceptible MBT; 2) those who had multiresistant MBT susceptible to all ATDs,
      other than isoniazid and rifampicin; 3) those with multidrug resistance. MBT
      genotyping in accordance with the polymorphism of the length of restriction
      fragments IS6110 has indicated that the strains of the families W and AI were
      prevalent in all the groups. However, the strains of mycobacteria of the W family
      were most frequently (62%) detected among the patients with tuberculosis with
      slight drug resistance. Treatment was performed in accordance with the data of
      tests of MBT for their susceptibility to chemical agents. Comparison of the
      efficiency of therapy failed to reveal any relationship of the genotype of the
      causative agent within the groups of patients with tuberculosis with different
      resistance of Mycobacteria, including those with slight drug resistance. At the
      same time, the pattern of drug susceptibility of MBT largely determined the
      frequency and trends of bacterial isolation cessation.

PMID- 15478556
TI  - [Ways of enhancing the effectiveness of bacterioscopic diagnosis of tuberculosis
      in general health care facilities in case of pilot areas of Russia].
AB  - The experience of researchers of the Central Research Institute of Tuberculosis,
      Russian Academy of Medical Sciences, in the pilot areas of Russia has made it
      possible to perfect approaches to improving a bacteriological diagnosis of
      tuberculosis in general health care facilities. A decisive role in enhancing the
      effectiveness of detection of patients with tuberculosis by the Ziel-Nielsen test
      is played by the following factors: training of laboratory personnel; provision
      of laboratories with high-grade equipment and reagents; introduction of the
      methods and techniques unified and approved by the Ministry of Health of the
      Russian Federation; regular supervision of jurisdictional laboratories; outside
      control of the quality of studies. Proper organization of examination of
      patients, including an effectual selection of patients to be examined, the
      observance of the established frequency of their examination, and provision of
      the required quality of a taken sample greatly affect the efficiency of a
      microscopic diagnosis of bacillary patients. In addition, the centralization of
      performed microbiological tests for tuberculosis in the most trained, certified,
      and licensed large laboratories exercising a centralized control of the quality
      of microbiological studies is optimal.

PMID- 15478555
TI  - [A role of the biological chip test in the determination of rifampicin resistance
      in Mycobacteria in adolescents with active pulmonary tuberculosis].
AB  - Forty-nine adolescents with active pulmonary tuberculosis were followed up to
      assess the biological chip test for the detection of rifampicin resistance in
      Mycobacterium tuberculosis (MBT). Rifampicin resistance (rpo B gene mutation) was
      detected in 22 (44.9%) patients. Disseminated processes were detected in a larger
      proportion of the patients with rifampicin resistance than in those with MBT
      susceptibility (63.6 and 40.7%, respectively (p < 0.05). Comparison of the data
      on MBT resistance and susceptibility, which had been obtained by bacteriological
      studies (nutrient medium cultuvations) and the biological chip test, revealed
      their agreement in 50% of the cases. A response could be showed after 2-3 months
      in the former case and after 2-3 days in the latter case. With the biological
      chip test, the resistance of MBT to rifampicin was additionally established in
      38.7% of the patients with negative cultivation tests on admission and during
      therapy. Follow-ups have demonstrated that MBT resistance to rifampicin preserves
      longer with the biological microchip test than that with nutrient medium
      cultivation.

PMID- 15478557
TI  - [Drug resistance of Mycobacterium tuberculosis of the genotype Beijing in
      imprisonment places in the Arkhangelsk Region].
AB  - The paper describes the molecular genetic characteristics of M. tuberculosis (MT)
      strains isolated from 114 patients with pulmonary tuberculosis in the
      penitentiary system of the Arkhangelsk Region. The sensibility to the first-line
      antituberculous drugs was determined by the radiometric technique BACTEC; rpoB
      gene mutations were identified by Inno-Lipa, genotyping was made by the RFLPA
      assay and spoligotyping. The spread of MT of the genotype Beijing in the
      penitentiary system was found to be 76.3%. The high rate (79.8%) of the
      clustering pattern is indicative of active transmission of tuberculosis. The
      transmission of the Beijing genotype MBT strains was higher (96.6%) than that of
      other genetypes (25.9%). A multifactorial analysis has shown that streptomycin
      resistance is independently associated with the infection with the strain of MBT
      of the genotype Beijing (p = 0.02); the circulation and active transmission of
      Beijing among the population present a human health threat and an endemic risk
      from the spread of drug-resistant pulmonary tuberculosis.

PMID- 15478558
TI  - [Changes in the levels of nitric oxide in the mononuclear cells and neutrophils
      of patients with tuberculosis with varying courses of pulmonary tuberculosis].
AB  - A hundred and forty four patients with different types of the course of pulmonary
      tuberculosis were examined. Before and 20 hours after incubation with BCG-killed
      cultures, mononuclear cells and neutrophils were used to estimate the level of
      generation of nitric oxide (NO) from the content of its stabile metabolites-
      nitrites determined by Griess reagent. Crucially active pulmonary tuberculosis
      was found to follow the increased leukocytic generation of NO. The most profound
      shifts occurred in the mononuclear cells. During a favorable involutional
      process, the mononuclear cells increased their baseline generation of NO and,
      moreover, preserved their potential for a responsive "nitric oxide burst" when
      they met a specific causative agent. In patients with acute pulmonary
      tuberculosis, the basal level of NO in the mononuclear cells was high, but their
      response to BCG proved to be decreased. In the neutrophils, the basal level of NO
      exhibited a significant scatter and their higher response to BCG was noted only
      during the involutional course of tuberculosis. Changes in the leukocytic levels
      of NO were related to the magnitude of a systemic inflammatory response, to the
      severity of respiratory failure, and to the rate of cellular lipid peroxidation.
      A clear relationship was observed between the nature of baseline changes in the
      values of NA and the efficiency of subsequent treatment.

PMID- 15478559
TI  - [Distribution of HLA antigens in patients with tuberculosis and healthy
      individuals in the Tatar population].
AB  - The paper presents the results of a study of the distribution of Class I HLA
      antigens in an ethnic Tatar group (in patients with pulmonary tuberculosis and
      healthy individuals) in 4 districts of Tatarstan. It has been ascertained that an
      association with HLA-B22 antigen exists in patients with active pulmonary
      tuberculosis.

PMID- 15478560
TI  - [Lung dysfunction in patients with mild chronic obstructive bronchitis].
AB  - VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TCL, TGV, RV, Ravt, Riin, Rex,
      DLCO-SS, PaO2, and PaO2 were determined in 33 patients with mild chronic
      obstructive lung disease (FEV1 > 70% of the normal value). All the patients were
      found to have impaired bronchial patency; most (63.6%) patients had lung volume
      and capacity changes, almost half (45.5%) the patients had pulmonary gas exchange
      dysfunction. Impaired bronchial patency mainly appeared as decreased MEF50,
      MEF15, and FEV1/VC%; altered lung volumes and capacities manifested chiefly by
      increased RV and decreased VC; pulmonary gas exchange dysfunction showed up
      primarily as lowered PaO2. The magnitude of the observed functional changes was
      generally slight. MEF50, MEF75, FEV1/VC%, and VC dropped to 59-20 and 79-70% of
      the normal value, respectively. RV increased up to 142-196% of the normal value;
      PaO2 reduced up to 79-60% mm Hg.

PMID- 15478561
TI  - [Role of radionuclide studies in the evaluation of the activity of a pathological
      process in the lymph nodes and lung of patients with tuberculosis].
AB  - The authors studied the activity of a pathological process in the lymph nodes of
      the mediastinum, by using 67Ga citrate and 99mTc, and pulmonary circulation with
      MAA-99mTc. Radionuclide studies have established that in new cases of respiratory
      tuberculosis, the function of lymph nodes recovers by 1.5 times higher than that
      in pretreated patients. In patients with destructive tuberculosis, pulmonary
      circulation restores insignificantly and slowly, particularly in a group of
      pretreated patients. This is explained by the fact that the lung fibrous changes
      available prior to therapy defy an evolutionary process.

PMID- 15478562
TI  - [The tissue and cellular reactions of the lung in drug-resistant tuberculosis].
AB  - The material obtained from 52 patients with drug-resistant fibrocavernous
      pulmonary tuberculosis was studied. Morphological studies established the
      progression of a process in 94.2% of the cases. There was a prevalence of an
      alternatively exudative tissue reaction, a generalization of the process with
      specific and non-specific changes in the lung, lesion to the vascular bed with a
      predominance of an exudative reaction, generalized nonspecific and specific
      bronchitis with impaired elimination of the intraalveolar contents and with the
      preserved extensive cellular infiltrates in the lung. Healing elements as the
      signs of the encapsulation of caseous necrosis, the proliferation of lymphoid
      elements, and a macrophageal response were simultaneously revealed, which
      provides evidence for that different modalities of pathogenetic therapy should be
      used.

PMID- 15478563
TI  - [Treatment of bronchial obstruction in patients with pulmonary tuberculosis].
AB  - Whether the main points of treatment for bronchial obstructive syndrome (BOS) in
      chronic obstructive lung disease (COLD) can be adapted for patients with
      pulmonary tuberculosis (PT) was studied. For this purpose, 435 patients with PT
      with signs of BOS (forced expiratory volume at 1 second (FEV1) < 80% of the
      normal values) were examined. To establish differences in the efficiency of
      therapy, according to the activity of a process and to the magnitude of the
      impaired architectonics of the respiratory system, three main groups of
      observation were formed: 1) patients with infiltrative PT (IPT); 2) those with
      fibrocavernous PT (FCPT); and 3) those with posttuberculous pneumosclerosis (PS).
      According to the severity of BOS, the patients were divided into 3 subgroups: 1)
      104 patients with FEV1 > 70% of the normal values; 2) 229 patients with FEV1 69
      50%; 3) 102 patients with FEV1 < 50%. The patients with IPT and FCPT received the
      conventional antituberculous therapy under respective clinical, laboratory, and X
      ray control. The patients with PS had no antituberculous therapy. All the
      patients underwent 3-month clinical and functional monitoring evaluating changes
      in life quality, by using the respiratory questionnaire of the Saint George
      hospital. The findings have led to the conclusion that the use of the proposed
      therapy for bronchial obstructive syndrome in patients with pulmonary
      tuberculosis was highly effective, promotes the amelioration of the degree of
      respiratory symptoms in patients with IPT by 2 to 8 times, in those with FCPT by
      more than 2-3 times, and in those with PS by 1.45-10 times. The differences in
      the efficiency of bronchodilator therapy depend on the baseline level of
      bronchial obstruction. In patients with pulmonary tuberculosis concurrent with
      BO, the use of current inhalation bronchodilator therapy results in a substantial
      increase in FEV1, which differentiates BOS in PT from COLD. The use of the
      proposed therapy in the multimodality treatment of patients with pulmonary
      tuberculosis showed no statistically significant differences in the changes in
      the degree of X-ray symptoms while this therapy permits acceleration of
      abacillation in patients with IPT by 16.8% and in those with FCPT by 14.8%.
      Effective bronchodilator therapy considerably enhances life quality in patients.
      Thus, early systematic and long-term performance of the bronchodilator therapy,
      based on the principles of bronchodilator therapy for COLD, in patients with PT
      concurrent with BOS may substantially enhance the efficiency of treatment in this
      category of patients.

PMID- 15478564
TI  - [Induction of an immune response to mycobacterial antigens by means of dendritic
      cells].
AB  - The study evaluated whether a vaccine can be designed by using dendritic cells
      loaded by mycobacterial antigens. A method for preparing murine dendritic cells
      from the bone-marrow precursors was modified. The dendritic cells were
      characterized by the expression of surface molecules by flow cytofluorometry. The
      study has shown that T lymphocytes can be primed in vivo by administering the
      dendritic cells expressing the protective Mycobacterium tuberculosis antigens
      H37Rv.

PMID- 15478565
TI  - Demystifying CINV control in the complex aging patient: assessing the
      complexities of the aging oncology patient.
AB  - Oncology nurses play a vital role in the management of chemotherapy-induced
      nausea and vomiting (CINV). Serotonin-receptor antagonists, neurokinin 1
      antagonists, and steroids can control nausea and vomiting associated with cancer
      chemotherapy, improving patients' abilities to tolerate and complete the full
      course of cancer treatment. Safe and effective management of CINV in older
      patients involves special considerations, including comorbidities, potential for
      drug-drug interactions and toxicities, physiologic changes related to aging, and
      concomitant use of complementary and alternative therapies. In this session, a
      multidisciplinary group of oncology specialists discussed the nursing
      considerations related to conventional and complementary management of CINV in
      this patient population.

PMID- 15478567
TI  - Optimizing patient care: minimizing the impact of chemotherapy-induced
      toxicities.
AB  - Research into reducing the side effects of anthracyclines and optimizing patient
      care and quality of life is constantly evolving. This program took a look at ways
      that oncology nurses can reduce the toxicities of conventional and novel
      chemotherapy regimens as well as addressing the erythropoietic agents used to
      treat patients with anemia.

PMID- 15478566
TI  - Meeting the challenges in cancer pain management.
AB  - Cancer pain, caused by the disease itself or its treatments, is common. This
      session discussed pain management strategies that nurses can share with patients
      experiencing pain. The program covered variables that must be considered when
      selecting an initial opioid for managing pain, the concept of opioid rotation for
      patients experiencing severe pain, neuropathy assessment and treatment, and the
      future of cancer pain management.

PMID- 15478568
TI  - Moving ahead: challenges with combination therapies for colorectal cancer.
AB  - The recent emergence of multiple combination chemotherapeutic regimens for
      colorectal cancer has expanded the options available to patients. Along with
      these new options come complex side-effect profiles that affect care management
      systems and patient lifestyles. This program used an interactive, case study
      approach to discuss the implications of these new treatments on patient education
      and nursing care.

PMID- 15478569
TI  - Issues of importance: maintaining comfort and compassion for patients in pain.
AB  - Addressing issues in the management of pain can create dilemmas for those caring
      for patients. This session examined the realities of current societal pressures,
      provider bias, and caregiver concerns in providing quality individualized pain
      management. This program also addressed how holistic care can improve the
      management of cancer pain.

PMID- 15478570
TI  - Effective interventions for CINV: NCCN Antiemesis Clinical Practice Guidelines in
      Oncology.
AB  - This session incorporated a case-study approach and interactive dialogue to
      provide an understanding of current antiemesis guidelines. The program was
      designed to illustrate ways that nurses can implement evidence-based practice
      into their daily clinical setting to successfully manage chemotherapy-induced
      nausea and vomiting.

PMID- 15478571
TI  - Future frontiers in the treatment of myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS), a group of bone marrow disorders characterized
      by the production of abnormally functioning, immature blood cells, are most
      prevalent in patients over 60 years of age. Supportive care has long been the
      mainstay of treatment; however, new clinical research shows promise for the
      treatment of MDS. This program focused on the pathophysiology of MDS, novel
      therapies for MDS, and key nursing considerations for treating these patients.

PMID- 15478572
TI  - Invasive fungal infections in the oncology patient: an overview of clinical
      manifestations and treatment.
AB  - This session addressed the different types of fungal infections and their risks
      seen in patients with cancer. The history of treatments used as well as new
      treatments, including those just approved and those still on the horizon, were
      covered. Risks and indications for the drugs also were discussed.

PMID- 15478573
TI  - New advances in chemotherapeutic and supportive care agents for the management of
      breast cancer patients.
AB  - A breast cancer diagnosis can be frightening and confusing for patients. This
      session addressed the new chemotherapeutic and supportive care agents available
      for the management of patients with breast cancer and the side effects associated
      with these new agents. Administration, pharmacology, and toxicities were
      addressed. In addition to providing insight into prevention and management of
      side effects of treatment, the speakers provided information on new clinical
      trials and agents on the horizon for treating this very heterogeneous group of
      patients with cancer.

PMID- 15478574
TI  - Unlocking the clinical mysteries of supportive care: a focus on chemotherapy
      induced neutropenia, anemia, and mucositis.
AB  - This program provided an overview of the nurse's role in risk assessment and
      supportive care for patients with hematologic toxicities, such as neutropenia,
      anemia, constipation, diarrhea, nausea and vomiting, anxiety, and depression.
      Speakers discussed the use of growth factors to avoid dose reductions or delays
      in chemotherapy treatment, especially patients with potentially curable tumor
      types.

PMID- 15478575
TI  - Melanoma update: staging, treatment, and symptom management.
AB  - Melanoma rates are increasing at an alarming rate, with 1 in 70 Americans
      developing melanoma annually. This session offered information for oncology
      nursing professionals to use in their day-to-day practice about the staging,
      treatment, symptom management, education, and care of patients with melanoma.
      Side effects of melanoma and its treatments were covered, including fatigue,
      depression, anorexia, and pruritus, among others.

PMID- 15478576
TI  - New approaches in safe handling of hazardous drugs.
AB  - This session provided an overview of the health effects of occupational exposure
      to hazardous drugs and provided information about specific steps that can be
      taken to reduce accidental exposure, such as reducing surface contamination, use
      of personal protective equipment, and proper disposal guidelines, among other
      safe practices. Tips for developing or auditing safety procedures in the
      workplace were provided as well.

PMID- 15478577
TI  - Managing patients through aggressive cancer therapies.
AB  - This session reviewed some of the more serious complications and problems
      associated with treatment and management of patients with head and neck cancer.
      Strategies to prevent or reduce the incidence and severity of toxicities were
      discussed. Additionally, the use of cytoprotective agents was presented,
      particularly the use of amifostine.

PMID- 15478578
TI  - Current topics in bone metastases.
AB  - Patients with cancer who have bone metastases may live for several years
      following diagnosis. However, skeletal disease significantly impacts quality of
      life, causing bone pain, pathologic fractures, spinal cord compression, and
      hypercalcemia. This program covered the challenges of treatment, new standards of
      care, advances in nursing, responsibilities in supportive care, and current
      trials investigating options for treatment-induced bone loss. The program ended
      with a call to nurses to become more active as patient advocates.

PMID- 15478579
TI  - Current topics in breast cancer for oncology nurses.
AB  - In this session, breast cancer experts provided updates on the changing practices
      in endocrine treatment, current chemotherapy and biologic regimens, and special
      considerations when treating patients with cardiac disease. Management of
      commonly encountered symptoms of breast cancer, such as osteoporosis and sexual
      and cognitive dysfunction, also were discussed.

PMID- 15478580
TI  - Advancing the assessment and treatment of mucositis.
AB  - Oral mucositis is inflammation of the mucosal oral and oropharyngeal tissues. It
      is a troubling and difficult side effect of cancer treatment. This program
      discussed the biology of oral mucositis and its effect on cancer therapy
      outcomes. Speakers covered the treatment goals for patients with oral mucositis
      and reviewed treatment options and related nursing implications.

PMID- 15478581
TI  - Advanced non-small cell lung cancer: current state of knowledge.
AB  - This program reviewed the latest treatment advances for advanced lung cancer and
      related symptom management. The program focused on appropriate interventions and
      research-based treatment guidelines for care of patients with advanced non-small
      cell lung cancer.

PMID- 15478582
TI  - Improving treatment for tumor lysis syndrome: strategies for every oncology
      nurse.
AB  - Tumor lysis syndrome (TLS) is an oncologic emergency that occurs when a large
      number of rapidly dividing cells is lysed. Patients with cancer who have massive
      tumor burden with cells that are rapidly dividing are at particular risk for this
      potentially life-threatening complication. This program discussed the risk
      factors for developing TLS, the laboratory data used to diagnose the syndrome,
      the signs and symptoms associated with each of the metabolic abnormalities
      related to the syndrome, and patient management.

PMID- 15478583
TI  - Clinical implications of targeting VEGF in solid tumors.
AB  - Conventional chemotherapy does not improve overall response rates in many
      patients with metastatic disease. Vascular endothelial growth factor (VEGF) has
      been identified as a target for novel therapeutics designed to inhibit tumor
      angiogenesis, which is essential for tumor growth and metastasis. This session
      provided nurses with information about the potential clinical implications of
      VEGFs, including proper administration, patient education, and side-effect
      management.

PMID- 15478584
TI  - Case studies in breast and colorectal cancer for the oncology nurse.
AB  - This program provided an overview of emerging trends in breast and colorectal
      chemotherapy and insight into evidence-based improvements in the role of the
      oncology nurse as a part of the treatment team. Case studies highlighted major
      side effects and patient management issues.

PMID- 15478585
TI  - Radioimmunotherapy for non-Hodgkin lymphoma (NHL): nursing and patient
      perspectives.
AB  - This session addressed the major clinical endpoints of radioimmunotherapy trials,
      dose calculation for single administration of a radioimmunotherapy product, and
      strategies for the education of patients and caregivers. Attendees learned about
      the benefits of radioimmunotherapy from the perspective of a survivor of non
      Hodgkin lymphoma.

PMID- 15478586
TI  - Update on extended adjuvant therapy options in breast cancer.
AB  - This program looked at extended adjuvant therapy options in breast cancer,
      focusing on adjuvant therapies in women who are postmenopausal with advanced
      breast cancer and disease progression following traditional antiestrogen therapy.
      Aromatase inhibitors and novel approaches to managing hormone-dependent breast
      cancer were covered, as well as associated nursing implications.

PMID- 15478587
TI  - EGFR-targeted therapy for patients with colorectal cancer: patient management and
      future directions.
AB  - The epidermal growth factor receptor (EGFR) signaling pathway is of particular
      relevance for patients with colorectal cancer (CRC); preclinical data indicate a
      role for EGFR in tumor cell growth, invasion, metastasis, and tumor angiogenesis.
      The goal of this program is to provide an overview of the EGFR signaling pathway
      as well as current and future treatment options for EGFR-targeted therapy in
      patients with CRC.

PMID- 15478588
TI  - Myths and facts about long-acting opioids in chronic pain: a multidisciplinary
      analysis.
AB  - Opioid analgesics have well-established efficacy in controlling chronic pain and
      improving patients' mood, function, and quality of life. Despite this, these
      agents continue to be underused in patients with moderate to severe pain who
      require almost continuous pain relief. This symposium reviewed evidence about
      opioid analgesics, presented methods of minimizing their adverse effects, and
      discussed dosing strategies for providing continuous, effective pain relief.

PMID- 15478589
TI  - Cancer treatment-induced diarrhea: interventions to minimize the roller coaster
      ride.
AB  - This program used a case-study approach to discuss interventions that nurses can
      implement in their daily clinical environment to minimize cancer treatment
      induced diarrhea. Manifestations of cancer treatment-induced diarrhea, medical
      treatment options, and nutritional interventions were covered.

PMID- 15478590
TI  - Current topics in colorectal cancer.
AB  - Much progress has been made in colorectal cancer (CRC) treatment over the past
      decade. This program provided a scientific review of CRC and information on
      current treatments and management of their side effects, new treatments under
      investigation, and special considerations when managing older patients.

PMID- 15478591
TI  - Chemotherapy-induced nausea and vomiting (CINV): prevention, detection, and
      treatment--how are we doing?
AB  - This program addressed prevention, detection, and treatment of chemotherapy
      induced nausea and vomiting, including a review of incidence and pathophysiology.
      Patient assessment, monitoring, and treatment as well as quality-of-life issues
      also were covered.

PMID- 15478592
TI  - The healing power of colony-stimulating factors.
AB  - This session applied an interactive case study format to explore the healing
      properties of colony-stimulating factors (CSFs). Diarrhea, oral mucositis, wound
      healing, and Crohn disease are four specific areas in which CSFs have had
      success. The presenters also covered the signs and symptoms of conditions for
      which CSFs may be helpful.

PMID- 15478593
TI  - Targeting apoptosis and DNA synthesis: understanding treatment concepts and
      nursing considerations.
AB  - This session dealt with targeting apoptosis and DNA synthesis via antisense
      therapy to block overproduction of Bcl-2. Speakers also discussed ongoing
      developments in and use of antisense therapies in hypercalcemia, multiple
      myeloma, lymphoma, and bladder cancer, as well as nursing considerations.

PMID- 15478594
TI  - Nursing considerations for nontraditional treatment approaches to hematologic
      malignancies.
AB  - This session addressed acute promyelocytic leukemia (APL), multiple myeloma, and
      myelodysplastic syndromes. In particular, arsenic trioxide as a treatment for
      APL, one of the most highly curable types of acute myeloid leukemia, was
      discussed. Speakers also discussed the use of combination regimens in clinical
      trials for multiple myeloma treatments and therapeutic agents in the treatment of
      myelodysplastic syndromes.

PMID- 15478595
TI  - A nursing focus on oral mucositis: a balanced approach to improving outcomes.
AB  - Oral mucositis is a common and difficult to manage side effect of cancer and its
      treatments. This session addressed the care and treatment of patients with oral
      mucositis and the consequences of this effect. Quality-of-life issues were
      covered as well as recent clinical data and trends in nursing care.

PMID- 15478596
TI  - Proteasome inhibition therapy: assessing the clinical implications in hematologic
      diseases.
AB  - This session addressed the use of proteasome inhibition therapy in multiple
      myeloma, specifically bortezomib. It also discussed various complications of
      multiple myeloma and cautions to be taken, specifically regarding osteolytic
      lesions and renal failure.

PMID- 15478597
TI  - Unraveling the complexities of targeted therapy treatment in cancer care.
AB  - This program discussed the rationale for treatment choices in non-Hodgkin
      lymphoma and HER-2 positive breast cancer. The mechanisms and management of
      infusion, cytokine-mediated, and allergic reactions related to monoclonal
      antibody (MOAB) therapy were covered, as well as a summary of the mechanisms of
      action and toxicities of MOAB therapy in breast cancer.

PMID- 15478598
TI  - Advances in taxane therapy for metastatic breast cancer.
AB  - This session discussed the use of taxanes in metastatic breast cancer therapy.
      Taxane toxicities, the mechanism of action, and efficacy were covered.
      Hypersensitivity, bone marrow toxicity, and other toxicities were detailed as
      well.

PMID- 15478599
TI  - Treating the older patient with leukemia, lymphoma, and myeloma.
AB  - This program focused on the challenges of treating older adults with leukemia,
      lymphoma, and myeloma; how older adults can be assessed to anticipate any age
      related barriers to therapy; and how emerging therapies and better side effect
      management offer older adults access to promising outcomes not possible years
      ago.

PMID- 15478600
TI  - Multiple myeloma: a new treatment paradigm.
AB  - This session discussed staging classifications, induction treatments, stem cell
      transplantation, experimental treatment options, and supportive care for patients
      with multiple myeloma. Several case studies were provided for audience members to
      consider various facets of the care of this patient population.

PMID- 15478601
TI  - [Analysis, identification and correction of some errors of model refseqs appeared
      in NCBI Human Gene Database by in silico cloning and experimental verification of
      novel human genes].
AB  - We found that human genome coding regions annotated by computers have different
      kinds of many errors in public domain through homologous BLAST of our cloned
      genes in non-redundant (nr) database, including insertions, deletions or
      mutations of one base pair or a segment in sequences at the cDNA level, or
      different permutation and combination of these errors. Basically, we use the
      three means for validating and identifying some errors of the model genes
      appeared in NCBI GENOME ANNOTATION PROJECT REFSEQS: (I) Evaluating the support
      degree of human EST clustering and draft human genome BLAST. (2) Preparation of
      chromosomal mapping of our verified genes and analysis of genomic organization of
      the genes. All of the exon/intron boundaries should be consistent with the GT/AG
      rule, and consensuses surrounding the splice boundaries should be found as well.
      (3) Experimental verification by RT-PCR of the in silico cloning genes and
      further by cDNA sequencing. And then we use the three means as reference: (1) Web
      searching or in silico cloning of the genes of different species, especially
      mouse and rat homologous genes, and thus judging the gene existence by ontology.
      (2) By using the released genes in public domain as standard, which should be
      highly homologous to our verified genes, especially the released human genes
      appeared in NCBI GENOME ANNOTATION PROJECT REFSEQS, we try to clone each a highly
      homologous complete gene similar to the released genes in public domain according
      to the strategy we developed in this paper. If we can not get it, our verified
      gene may be correct and the released gene in public domain may be wrong. (3) To
      find more evidence, we verified our cloned genes by RT-PCR or hybrid technique.
      Here we list some errors we found from NCBI GENOME ANNOTATION PROJECT REFSEQs:
      (1) Insert a base in the ORF by mistake which causes the frame shift of the
      coding amino acid. In detail, abase in the ORF of a gene is a redundant
      insertion, which causes a reading frame shift in the translation of an
      alternative protein, such as LOC124919 is wrong form of C17 orf32 (with mouse and
      rat orthologs determined by us). (2) Put together by mistake (with force). This
      is a wrong assembly of non-relating cDNA segment, such as LOC147007 is wrong form
      of C17orf32. (3) Mistakenly insert a base or one section of cDNA in the ORF which
      causes it ending beforehand, only coding cDNA sequence of N-terminal amino acids,
      incomplete. For example, LOC123722 is wrong form of SPRYD1, and even the human
      hypothetical gene LOC126250 or PDCD5 is wrong form of our PDCD5 (TFAR19). (4)
      Incomplete, only coding cDNA sequence of C-terminal amino acids. For example,
      human LOC149076 and mouse LOC230761 are wrong form of our verified human ZNF362
      and mouse Zfp362, respectively. (5) Incomplete, only coding one section of coding
      protein cDNA sequence of correct gene ORF, lacking N-terminal and C-terminal
      amino acids sequence, and at the same time, mistakenly anticipates the first non
      initiation codon amino acid of the incomplete protein amino acid as the
      initiation codon, e.g. anticipating L as M. For example, LOC200084 is wrong form
      of ZNF362. (6) Mistakenly insert a base or one section of cDNA in the ORF,
      wrongly causing unwanted termination codon before the insertion, so the coding
      protein lacks the first part of the amino acids. For example, the GenBank Acc.
      No. AL096883 ( LOCUS No. HS323M22B) is wrong form of an experimentally verified
      human NM_012263 with mouse ortholog of BC010510 determined. (7) It may regard the
      polluted genomic sequence as complete gene cDNA sequence and anticipate the so
      called single exon gene, even the real one, only a small ORF in the very long
      single exon mRNA, while there really exists termination code in the same phase of
      the upper part of the ORF initiation code, no other characters accord with the
      gene's condition. For example, LOC91126 is wrong form of ZNF362. (8) The
      anticipated genes only have ORF which has no EST proofs on both terminal sides.
      Depending on this ORF, a complete gene cDNA with double support of EST and human
      genome (there are termination codes at the same phase of the upper part of ORF)
      which indicates the anticipated ORF reference sequence may be incorrect. For
      example, LOC164395 may be wrong form of novel human gene bankit4590055. (9) A
      similar but smaller protein-coding gene is anticipated in the range of the human
      genome sequence that has the support of EST experimental proof, so other new
      anticipated gene may be incorrect. For example, LOC167563 may be wrong form of
      CMYA5. However,these errors can be corrected or avoided by using our strategy.
      Here we give one example in detail: Comparision of the sequence SPRYD1 with human
      hypothetical gene LOC123722. The TAA bases in the position of 478-480 in
      LOC123722 cDNA is redundant, which causes a reading frame shift in the
      translation of an alternative protein. The redundancy of GTAAA of LOC123722 is
      not supported by our experimental clone,and is almost fully rejected by human EST
      alignment, and is shown as the next intron sequence by genomic GT/AG organization
      analysis. The verification of cDNA or genomic DNA sequence of SPRYD1 implies that
      LOC123722 has a wrong stop codon within its ORF because of the prediction
      program, thus being not complete cds. To sum up, by combining bioinformatics
      analyses with experimental verification, we have found that there are many errors
      of at least nine kinds appeared in NCBI GENOME ANNOTATION PROJECT REFSEQs through
      BLAST of our cloned genes in non-redundant database, and our strategy is helpful
      in correcting them, such as LOC14907, LOC200084 and LOC91126 (all of them should
      be ZNF362, but are three different kinds of wrong forms of ZNF362), three model
      reference sequences predicted from NCBI contig NT_004511 by automated
      computational analysis using gene prediction method, or such as LOC124919 and
      LOC147007 (both should be C17orf32, but are two different kinds of wrong forms of
      C17orf32), two model reference sequences predicted from NCBI contig NT_010808 by
      automated computational analysis using gene prediction method. Therefore, the
      correct identification and annotation of novel human genes may be still a heavy
      task, which can be finished within a long period of time. So human genome coding
      regions annotated by computer should be used with caution. The articles published
      in the past did not clearly point out the existence of mistakes in the NCBI human
      gene mode reference sequence. At the Seventh International Human Genome
      Conference held in April 2002, we first published the researching result on this
      aspect in the communication form of Posterly insert a base or one section of cDNA
      in the ORF, wrongly causing unwanted termination codon before the insertion, so
      the coding protein lacks the first part of the amino acids. For example, the
      GenBank Acc. No. AL096883 ( LOCUS No. HS323M22B) is wrong form of an
      experimentally verified human NM_012263 with mouse ortholog of BC010510
      determined. (7) It may regard the polluted genomic sequence as complete gene cDNA
      sequence and anticipate the so-called single exon gene, even the real one, only a
      small ORF in the very long single exon mRNA, while there really exists
      termination code in the same phase of the upper part of the ORF initiation code,
      no other characters accord with the gene's condition. For example, LOC91126 is
      wrong form of ZNF362. (8) The anticipated genes only have ORF which has no EST
      proofs on both terminal sides. Depending on this ORF, a complete gene cDNA with
      double support of EST and human genome (there are termination codes at the same
      phase of the upper part of ORF) which indicates the anticipated ORF reference
      sequence may be incorrect. For example, LOC164395 may be wrong form of novel
      human gene bankit4590055. (9) A similar but smaller protein-coding gene is
      anticipated in the range of the human genome sequence that has the support of EST
      experimental proof, so other new anticipated gene may be incorrect. For example,
      LOC167563 may be wrong form of CMYA5. However, these errors can be corrected or
      avoided by using our strategy. Here we give one example in detail: Comparision of
      the sequence SPRYD1 with human hypothetical gene LOC123722. The TAA bases in the
      position of 478-480 in LOC123722 cDNA is redundant, which causes a reading frame
      shift in the translation of an alternative protein. The redundancy of GTAAA of
      LOC123722 is not supported by our experimental clone, and is almost fully
      rejected by human EST alignment, and is shown as the next intron sequence by
      genomic GT/AG organization analysis. The verification of cDNA or genomic DNA
      sequence of SPRYD1 implies that LOC123722 has a wrong stop codon within its ORF
      because of the prediction program, thus being not complete cds. To sum up, by
      combining bioinformatics analyses with experimental verification, we have found
      that there are many errors of at least nine kinds appeared in NCBI GENOME
      ANNOTATION PROJECT REFSEQs through BLAST of our cloned genes in non-redundant
      database, and our strategy is helpful in correcting them, such as LOC14907,
      LOC200084 and LOC91126 (all of them should be ZNF362, but are three different
      kinds of wrong forms of ZNF362), three model reference sequences predicted from
      NCBI contig NT_004511 by automated computational analysis using gene prediction
      method, or such as LOC124919 and LOC147007 (both should be C17orf32, but are two
      different kinds of wrong forms of C17orf32), two model reference sequences
      predicted from NCBI contig NT_010808 by automated computational analysis using
      gene prediction method. Therefore, the correct identification and annotation of
      novel human genes may be still a heavy task, which can be finished within a long
      period of time. So human genome coding regions annotated by computer should be
      used with caution. (ABSTRACT TRUNCATED)

PMID- 15478602
TI  - Preliminary analysis of CDK2 sequence and its nuclear import.
AB  - We constructed the plasmids encoding enhanced green fluorescent protein (EGFP)
      tagged wild type cyclin-dependent kinase 2(CDK2) (pEGFP-CDK2) and CDK2 deletion
      mutants (pEGFP-CDK2N and pEGFP-CDK2C, lacking the last C-terminal and the first N
      terminal 97 amino acids of CDK2, respectively) and transfected them into HeLa
      cell line and CHO cell line. After synchronization, green fluorescent signals
      were detected mainly in nucleus of the cells transfected with pEGFP-CDK2 and
      predominantly in cytoplasm of the cells transfected with the two mutant CDK2
      constructs. Our results suggested that there were no nuclear-import signals in
      CDK2 and that CDK2 nuclear import might be mediated by association with other
      proteins through the three-dimensional structure formed by amino acids including
      those from the N- and C-terminal regions of CDK2.

PMID- 15478603
TI  - [Studying dystrophin gene deletion in the northeast of China and applicating].
AB  - To detect the distribution characteristics of dystrophin gene deletions of the
      DMD/BMD patients in the northeast of China and apply for prenatal gene diagnosis,
      we have analyzed the distribution of the breakpoints of the deleted-patients and
      the optimized primer-assembly after screening deletions of 120 DMD/BMD patients
      via multiplex PCR with 12-pair primers and male high-risk fetuses have been
      detected deletion by multiplex PCR. Results indicated the deletion frequency was
      49.2%, about 66.4% deletion breakpoints positioned in introns 44-52, intron 50
      was the highest breakpoint (14.8%). The optimized four-primer-assembly was the
      primers of exon 48, 51, 45 and 8, which could detect 41.7% deletions of all
      cases; 9 deletions male ones of 29 high-risk fetuses were detected, who had the
      same deletion-segments as their probands. For the first time screening deletions
      of DMD/BMD patients in the northeast of China, we have found distribution of the
      deletions mainly lied in two hot-spots, neighboring regions of exon 8 might be a
      real deletion 'hot spot' in this area compared with other areas of our country;
      introns 44-52 of dystrophin gene were highly unstable and prone to break: intron
      44 was more stable than the whole molecular region of 'central deletion hot spot'
      and the unstability of intron 50 changed along with the regional and ethnic
      difference; the optimized primer-assembly provided the short-cut for detecting
      patients and making prenatal gene diagnosis, especially it's feasible and
      advantageous for the isolated pedigrees.

PMID- 15478604
TI  - [Significance of methylation and abnormal expression of p16 gene in endometrial
      carcinoma].
AB  - The tumor suppressor gene p16, located on chromosome 9p21, encodes the cell cycle
      regulatory protein, p16. Inactivation of the p16 gene could lead to uncontrolled
      cell growth. It was examined that methylation of the p16 gene 5'CpG island of the
      tumor suppressor gene may be an important mechanism for transcriptional
      inactivation. In order to determine the role of methylation status of the 5'CpG
      island and abnormal expression of incarcinogenesis of endometrial carcinoma (EC),
      Methylation-Specific PCR (MSP) was used to determine the methylation status of
      p16 gene 5'CpG islands of 62 cases of EC. Loss or decrease of p16 expression was
      analyzed by immunohistochemistry (IHC) and homozygous deletion of exon1 (E1) and
      exon2 (E2) was determined by complex PCR. Ten specimens of normal tissues and
      adjacent tissues of tumor displayed no methylation and showed normal expression
      of p16. In E1 and E2 of the 62 EC, we found that 24.2% (15/62) were methylated,
      54.8% (33/62) lost or reduced p16 expression, 16.1% (10/62) and 30.6% (19/62) had
      deletions of E1 and E2 respectively. There were 9.68% (6/62) and 46.6% (29/62)
      deletions of both or either of E1 and E2 respectively. Inactivation of p16 gene
      is a frequent event and positively correlated with pathological grades and
      clinical stages in EC. p16 gene methylation was an important event in the
      development of EC. MSP is an accurate and relatively simple method for evaluating
      the methylation status of a related gene.

PMID- 15478605
TI  - Interaction of two classes of release factors from Euplotes octocarinatus.
AB  - Translation termination on the ribosome is an essential process for cell
      viability. This process is maintained by two classes of peptide release factors
      (RF1/RF2, RF3 and eRF1, eRF3 in prokaryotes and eukaryotes, respectively). In
      protozoa ciliates Euplotes octocarinatus, an unicellular eukaryotes, universal
      stop codon UGA is reassigned for cysteine suggesting the specificity of evolution
      of translation termination system. We cloned two classes of release factors from
      Euplotes octocarinatus previously. In this paper, three in-frame stop codons UGA
      in Eo-eRF3 gene were mutated mediated by PCR site directed mutagenesis method.
      The interaction between eRF1 and eRF3 from E. octocarinatus was assayed in vivo
      using Yeast Two-hybrid System, which has an advantage of highly sensitivity. The
      results showed that the eRF1 x eRF3 complex was formed in living cells to
      function in the process of translation termination, differing from that in
      prokaryotes in which RF1/RF2 and RF3 function separately. The evolution of
      translation termination of life-form was analyzed using phylogenetic tree of
      amino acids sequences of RFs (32 (e) RF1s and 24 (e) RF3s) obtained from GenBank.
      Two classes of RFs are useful information in analysis of evolution of life-form
      and further elucidation of mechanism of translation termination of protein
      synthesis on ribosome.

PMID- 15478606
TI  - [Cloning of four members of giant panda Dmrt genes].
AB  - Sex determining genes Mab-3 of C. elegans and Doublesex of Drosophila contain a
      common DNA binding motif called DM (Doublesex and Mab-3) domain, both of which
      regulate similar aspects of sexual development. Human Doublesex-related gene
      DMRT1 has been identified, which also contains the conserved DM-related DNA
      binding domain and plays an essential role in gonadal differentiation. We
      amplified genomic DNA of the giant panda using the DM degenerate primers and
      detected two bands, approximately 140 bp and 250 bp. After cloned into T-easy
      vector and sequenced, four sequences showed high homology with the DM domain.
      Amino acid sequence of the first clone is 100% identical with the Dmrt1 of human,
      mouse and pig, hence we named it as pDmrt1. The second clone is 96% identical
      with human DMRTB1, and the third one 100% with the Dmrt3 of mouse and medaka,
      which were named as pDmrtb1 and pDmrt3 respectively. The last sequence contains
      an intron of 116 bp within the DM domain, which encodes an amino acid sequence
      100% identical with human DMRTC2, accordingly we named it as pDmrtc2. Based on
      similarities of amino acid sequences of the DM domain, Dmrt protein sequences
      from human, mouse and giant panda were included in a phylogenetic tree. They
      revealed seven distinct subgroups: Dmrt1, Dmrt2, Dmrt3, Dmrt4 (DMRTA1), Dmrt5
      (DMRTA2), Dmrt6 (DMRTB1) and Dmrt7 (DMRTC2). Our results further reveal the
      unexpected complexity and the evolutionary conservation of the DM domain gene
      family in both invertebrates and vertebrates.

PMID- 15478607
TI  - [Advanced methods of preparing pachytene bivalents and high resolution multiple
      bands of zebrafish (Danio rerio)].
AB  - The pachytene bivalents with high-resolution multiple G bands of zebrafish were
      obtained after the treatment with alkaline hypotonic solution and high
      concentration of chloroform fixative solution. When comparing six group
      chromosomes from different pachytene specimens, the characteristic and the number
      of bands were well matched. In order to systematize this technique and get stable
      result, we summarize the preparation procedure of the zebrafish bivalents. The 6
      month-old to one-year-old zebrafish whose spermary appears ivory-white and
      opaque, is good material. The whole testis should be treated with hypotonic
      solution for 1.5 approximately 2 h at room temperature. Then, the testes were
      fixed for 20 min in high chloroform fixative solution (chloroform: methanol:
      acetic acid, 3: 6:1), and fixed in Carnoy's solution (methanol: acetic acid, 3:1)
      for two times. In addition, with the treatment of restriction endonuclease Alu I
      directed in situ nick translation, we successfully obtained well-resolved
      restrictive endonuclease banding of zebrafish bivalents, which was considered as
      G-like band patterns. The aging of the specimen is also important factor, should
      let them dry at room temperature for one week. The application of these methods
      in cytogenetics research of zebrafish and other fish can be expected.
      Construction of the steady technique system to prepare high resolution banding
      bivalents and idiogram of zebrafish is the basement to found stable and accurate
      framework for physical map.

PMID- 15478608
TI  - [Identification and analysis of a novel microsatellite marker flanking porcine
      myostatin gene (MSTN)].
AB  - In animal breeding, microsatellite marker plays an important role in constructing
      genetic maps, QTL mapping and function analysis of structural genes. Myostatin,
      also known as GDF8, is a negative regulator of skeletal muscle mass and, in
      swine, it is evidenced to be related to birth weight and average daily gain from
      60 kg to 100 kg of body weight. In present study, by subcloning and sequencing,we
      identified a novel microsatellite marker which is useful for fine QTL mapping for
      meat traits. A BAC clone containing porcine MSTN was extracted and digested with
      EcoR I to recover the fragment of > 4 kb for subcloning in pGEM-3zf (+).
      Sequencing and alignment results showed that this subcloned fragment was not from
      porcine MSTN, but included a tandem repeat of (TG) 13, which is a novel
      microsatellite marker (GenBank accession number: AF454400) flanking MSTN. To
      exclude its vector origin we designed specific primers flanking this marker and
      successfully amplified this fragment from porcine genome. Through a pedigree
      analysis of a double-muscled Yorshire strain, we found that it is inherited in a
      co-dominant manner. We also checked the gene frequencies of this locus in 381
      unrelated individuals of 7 pig breeds, namely Laiwu,Landrace, Yorkshire,Duroc,
      Peterian, Min and Erhualian. Only two alleles were detected, the repeating number
      of which are 13 (allele A) and 19 (allele B) respectively, which indicated that
      it is a low poly morphic microsatellite marker. In addition, the frequencies of
      the two alleles are different between the two types of pig breeds, while allele A
      is dominant in Chinese local breeds, allele B is dominant in imported breeds.
      Alignment with AY208121 indicate that this locus is located 42 kb downstream of
      porcine MSTN. We speculate that this microsatellite DNA is an important marker
      both in fine QTL mapping for meat traits and in the expression study of porcine
      MSTN.

PMID- 15478609
TI  - [Cloning and primary analysis of spt1 as a ncRNA candidate gene].
AB  - In a process of screening mouse embryonic cDNA library with suc2 signal sequence
      trap, a strongly positive clone named spt1 was obtained repeatedly. Analysis of
      spt1 shows that the inserted sequence is 697 bp containing 37 start codons (ATG)
      and 80 stop codons (TGA, TAG, TAA), and there is no potential open reading fame
      in it. Similarity search by BLAST indicates that the sequence locates in the long
      arm of 17th chromosome, and no known genes show significant similarity with it.
      Northern blot and RT-PCR give positive signal specifically in ovary tissue, the
      full length of spt1 is about 4. 5 approximately 5.0 kb. Yeast transformation and
      sequence truncation experiment suggested that spt1 could mediate the secretion of
      invertase. Hence, spt1 may be part of a novel ncRNA gene which is involved in
      protein secretion.

PMID- 15478610
TI  - [Construction and identification on enriched microsatellite library from yak
      genome].
AB  - We constructed the first microsatellite-enriched library of yak according to the
      strong affinity between biotin and streptavidin. The method included ligation of
      300 approximately 1 000 bp enzyme-digested fragments and adaptors, affinity
      capture of microsatellite repeat using biotinylated oligoprobe ((CA)12, (CCG) 8,
      (CAG)8, (TTTC) 8) attached to streptavidin-coated magnetic beads, PCR
      amplification using the 21-mer adaptor oligonucleotide as primer to obtain double
      stranded targeted fragments, religated into pMD18-T vector and transformed to
      DH5alpha. The results of sequencing showed that 37 of 48 readable sequences
      contained microsatellites indicating a high degree of microsatellite enrichment.
      The new polymorphic microsatellite markers we have identified and characterized
      will contribute to the yak genetic linkage mapping, molecular evolution and
      phylogenetic studies, marker assistant selection and QTLs location of yak main
      economic traits.

PMID- 15478611
TI  - [The developmental changes of GHR and IGF-1R gene expressions in porcine
      hypothalamus and pituitary].
AB  - GH and IGF-1 may serve as negative feedback factors to regulate GH secretion from
      pituitary by binding to their respective receptors in hypothalamus and/or
      pituitary. In order to evaluate the line-specific developmental patterns of
      negative feedback regulation of GH secretion, Erhualian (EHL) and Large White
      (LW) pigs with significant difference in growth rate were employed in present
      study to investigate the developmental changes of GH receptor (GHR) mRNA and type
      1 IGF receptor (IGF-1R) mRNA in hypothalamus and pituitary from birth till 180
      days of age by relative quantitative RT-PCR. Pigs were sampled at birth, 3 , 20,
      30, 90, 120 and 180 days of age respectively. Hypothalamic GHR mRNA was expressed
      according to an age-dependent manner, being low at birth, then increased steadily
      till day 120, followed by a decrease (P < 0.05) at the age of 180 days,
      suggesting that the sensitivity of hypothalamus to the GH negative feedback
      influence increase steadily during fast-growing period. LW boars expressed higher
      level of GHR mRNA than EHL boars (P < 0. 05) in hypothalamus. In pituitary,
      however, the GHR mRNA level was not significantly correlated with the breeds and
      age. The results suggested that GH might act mainly at the level of hypothalamus
      to regulate GH secretion. In contrast, the expression of IGF-1R mRNA exhibited
      line-specific developmental patterns in pituitary but not in hypothalamus.
      Hypothalamic expression of IGF-1R mRNA was abundant but did not show significant
      differences between ages, groups or lines. In pituitary, however, the IGF-1R mRNA
      expression was found to be high at birth both in EHL and LW pigs, subsequently
      declined till day 20, then followed by a slow rise reaching the second peak at
      the age of 90 days. At the age of 180 days, the pituitary IGF-1R mRNA level was
      higher in EHL pigs than that in LW pigs (P < 0.05), but the opposite was true at
      the age of 30 and 90 days. These results suggest that the site for receiving the
      feedback signal of IGF-1 is more likely in pituitary rather than in hypothalamus
      in the pig.

PMID- 15478612
TI  - [Cloning and analysis of six full-length cDNA similar to sheep KAP6-1 from
      cashmere goat].
AB  - Cashmere is the fiber of kings, produced from the cashmere goat (Capra hircus).
      Cashmere fabric has little squama. Due to its lightness cashmere feels smooth and
      silky. An intriguing feature of cashmere structure is multiplicity of the hair
      keratin proteins with distinctive amino acid compositions. To study the role and
      regulation of one of these keratins, we used the SMART ( switching mechanism at
      5' end of RNA transcript) technology to construct a cDNA library of skin tissue
      from an Inner Mongolia male cashmere goat. A total of 636 cDNA sequences were
      obtained by randomly sequenced from 5' of cDNA library. Sequence comparison with
      the GenBank database confirmed that there are 41 sequences showed high nucleotide
      sequence identity in the coding region with sheep keratin associated protein 6-1
      (KAP6-1). They represent six different cDNAs (The accession numbers in GenBenk
      are AY310749, AY310750, AY310751, AY310752, AY310753 and AY310754, respectively).
      They are full-length cDNAs according to the known KAP6-1 genomic gene sequences
      of sheep. From the nucleotide sequences the open reading frames were identified,
      that encoded six basic proteins of 82, 84, 71, 71, 83, 83 amino acids,
      respectively, with a combined glycine and tyrosine content of about 60%. Compared
      analysis showed that the KAPs from goats shared more than 55.4% identities in
      nucleotide sequences and more than 79.8% identities in amino acid sequences with
      each other, and shared highest identities (81.9% approximately 98.8%) with KAP6-1
      from sheep. The KAP6s from different animal species shared more than 50%
      identities in amino acid sequences with each other.

PMID- 15478613
TI  - Cloning and developmental and tissue-specific expression of banana (Musa
      acuminate AAA) lectin gene.
AB  - A cDNA encoding banana lectin (BanLec) was obtained by using RT-PCR from banana
      fruit and sequenced. Comparison of this cDNA sequence with the sequence of BanLec
      gene registered in GenBank (Accession No. AF001527) showed that both sequences
      shared high similarity with only nine nucleotieds and four amino acids
      difference. RT-PCR analysis of the expression patterns of BanLec gene in
      different tissues and different fruit ripening stages of banana suggested that
      this cDNA not only expressed specifically in fruit but also expressed
      developmentally during fruit ripening. Relative quantification of expression
      level of BanLec gene in different tissues and different ripening stages were
      carried out by using computer software.

PMID- 15478614
TI  - [Fertility alteration of male sterile rice line annong S-1 and the expression of
      fertility related aprt gene].
AB  - The thermo-sensitive point and the thermo-sensitive stage for fertility
      alteration in the thermo-sensitive genic male sterile (TGMS) line Annong S-1 were
      studied. In nature environment and green house,the leaf, root and young panicle
      were treated by low and high temperature respectively. In total, 8 treatments
      were carried out. Results indicated that during the thermo-sensitive stage of
      fertility alteration, in high temperature environmental conditions, the low
      temperature treatment in the root did not significantly induce Annong S-1 to be
      fertile, while the low temperature treatment in young panicle obviously induced
      Annong S-1 to be fertile. Therefore, the thermo-sensitive point of Annong S-1 is
      the young panicle. The stage of fertility alteration was also investigated.
      Results indicated that alteration occurred in the phase from the formation of
      pollen mother cell to the tetrad of miosis. aprt gene is related the male
      sterility. The expression of aprt gene in root,young panicle and leaf were
      investigated by RT-PCR respectively. In young panicle, the expression of aprt
      gene was greatly down regulated by high temperature, while in root and leaf the
      expressions have no great changes. These data show that the young panicle is
      sensitive to temperature change. The result also supported that the young panicle
      is the thermo-sensitive point of Annong S-1 in the fertility alteration. These
      conclusions can be used to direct in hybrid rice seed production.

PMID- 15478615
TI  - [Endosperm-specific expression of the ferritin gene in transgenic rice (Oryza
      sativa L.) results in increased iron content of milling rice].
AB  - Iron deficiency is the most widespread micronutrient deficiency world-wild, and
      is estimated to affect about 30% of the world population. To increase the iron
      content of rice in Chinese, the 764 bp cDNA of ferritin gene was cloned from
      soybean (Phaseolus limensis), and constructed between the 1 353 bp rice glutelin
      GluB-1 promoter and NOS terminator in a binary vector pCAMIBA1301. The
      constructed pYF1067 vector was introduced into Agrobacterium strain EHA105, and
      used for transformation of the primary callus derived from immature embryos of a
      high-yielding rice ( Oryza sativa L. ssp. japonica) variety Wuxiangjin 9. Under
      the selection on hygromycin-containing medium, seventeen independent transgenic
      rice lines, total more than 80 transgenic plants, were finally regenerated, and
      most of these transgenic rice plants grew normally. PCR and Southern blot
      analysis of total DNA from primary transformants confirmed that one to three
      copies of the transgenes integrated into the genome of most of the transgenic
      plants, and they could be stably transmitted into the progeny of the transgenic
      rice. Northern blot analysis showed that the ferritin gene could specifically
      express in the endosperm of transgenic rice with high level, while no or low
      expression in leaves. The expression level varied among different independent
      transgenic rice plants. There was a significant effect of the high-expression of
      ferritin on the increased iron content in transgenic rice, the iron content in
      the milling rice of transgenic rice was up to 64% higher than that of the
      untransformed wild-type plant, whereas no significant alteration of the zinc
      level occurred between these two type rice plants.

PMID- 15478616
TI  - [Site-directed mutagenesis and promoter functional analysis of RM07 DNA fragment
      from Halobacterium halobium in Escherichia coli].
AB  - The RM07 DNA fragment from Halobacterium halobium was inserted upstream of
      chloramphenicol acetyltransferase (cat) reporter gene in pKK232-8 in two
      different orientations (positively or negatively), generating the RM07-cat fusion
      plasmids pRM07-1 (+) and pRM07-1 (-). These two plasmids and pKK232-8 were
      transformed into Escherichia coli HB101 respectively, then the antibiotic
      resistance level and the chloramphenicol acetyltransferase protein concentration
      of different transformants were detected. The research results revealed that
      HB101/pRM07-1 (+) was resistant to chloramphenicol and could grow on the plate
      containing chloramphenicol, but HB101/pRM07-1 (-) and HB101/pKK232-8 were
      sensitive to it. Therefore, the results suggested that the positive RM07 fragment
      had promoter activity in Escherichia coli while the negative RM07 fragment did
      not. Site-directed mutagenesis of RM07 was performed by PCR mutagenesis method.
      The effect of specific nucleotide mutations on the chloramphenicol resistance
      level of different transformants was detected. The different transformants
      containing different nucleotide mutations were inoculated on the plates
      containing various concentrations of chloramphenicol and then incubated at the
      same time. The change of chloramphenicol resistance level reflected the change of
      promoter activity. By using this method, the important nucleotide responsible for
      the promoter function of RM07 in Escherichia coli was determined. The promoter
      activity of RM07 in Escherichia coli was also improved greatly by modifying the
      nucleotide component.

PMID- 15478617
TI  - [Issues on association studies on complex diseases].
AB  - Association study is widely used in elucidating genetic basis of complex diseases
      such as cardiovascular diseases, type 2 diabetes, essential hypertension and
      obesity. Some issues were discussed in the review, which include defining and
      controlling of confounding effects, selection of candidate genes and single
      nucleotide polymorphisms (SNPs), application of intermediate phenotype and
      haplotype analyses as well as judgement of the result in association studies.
      Population stratification is one of the major causes of confounding in
      association studies. It could be reduced by selecting relatives of affected
      patients as control, genome control and by using isolated populations which have
      higher homogeneity in genetic background. A candidate gene could be selected
      because of its' biological association with some disease or being congenerous to
      a known gene related to the disease. Appropriate application of intermediate
      phenotype of diseases and haplotype analyses may increase the opportunity to
      obtain meaningful findings in association studies. An optimal study design,
      sufficient sample size and proper controls, in conjunction of modern statistic
      analyses, association analyses would exert its effect on studies on
      susceptibility of human common diseases.

PMID- 15478618
TI  - [Clinical evaluation of arteriosclerosis using high sensitive CRP in multiphasic
      screening].
AB  - In order to identify the chronic inflammation, hsCRP measurement at several time
      are recommended. The continuous higher value of CRP is observed as the signal of
      the chronic inflammation. In this case the average of CRP was more than 0.15mg/dl
      and the standard deviation was less than 100%. In this study, the hsCRP showed
      the biggest AUC (Aria Under Curve) at acute myocardial infarction (AMI). The
      blood pressure showed the biggest AUC at stroke. The event rate for AMI of
      patients who have the continuous higher CRP value is higher than the normal
      control. The relative risk for AMI is 20 fold. On the other hand, the relative
      risk for stroke is less than 1 fold. The key factor of the disease was suggested
      difference between AMI and stroke.

PMID- 15478619
TI  - Spontaneous migration of acute promyelocytic leukemia cells beneath cultured bone
      marrow adipocytes with matched expression of the major histocompatibility
      complex.
AB  - Leptin, secreted by adipocytes in bone marrow stimulates proliferation of acute
      myeloid leukemia cells. PML-RARalpha-expressing acute promyelocytic leukemia
      (APL) cells express high levels of leptin receptor (OB-R). Adipocytes derived
      from mesenchymal stem cells (MSC) protect APL cells from drug-induced apoptosis
      partially through the interaction of the membrane-bound form of leptin and OB-R.
      We report that when NB4 APL cells migrated beneath a cultured MSC-derived
      adipocyte layer, apoptosis in most of the cells below the adipocytes was blocked.
      Major histocompatibility complex (MHC) expression of NB4 cells and MSCs matched
      (both were HLA-DR negative and HLA-ABC positive). This match in MHC expression
      may play a role in the intimate cell-to-cell interactions that support the anti
      apoptotic effects of the membrane-bound leptin signaling pathway.

PMID- 15478620
TI  - [The rate of airflow limitation among the elderly undergoing spirometry in a
      university hospital].
AB  - The aim of this study was to examine the rate of airflow limitation among the
      elderly undergoing spirometry prior to surgical operation, and to evaluate
      whether or not spirometry is useful for the early detection of COPD. A total of
      3,086 patients (1,717 men and 1,369 women) ranging in age from 40 to 93 underwent
      screening spirometry from January to December 2003 in Tokyo Medical and Dental
      University Hospital. Among the total population, 2,135 patients (1,188 men and
      947 women) were ordered to undergo the spirometry prior to surgical operation,
      airflow limitation (FEV1/FVC < 70%) was observed in 19.5% (n=417) of the cases
      and was considerably more frequent in men than in women(27.0%[n=321] vs.
      10.1%[n=96]). The rate of FEV1/FVC < 70% in those 2,135 patients increased with
      age: 6.2%, 9.9%, 19.2%, 32.5% and 34.1% of patients in their 40s, 50s, 60s, 70s,
      80s and over, respectively. Among the patients with airflow limitation, 35% of
      the cases revealed FEV1 > or = 80% predicted; 50%, 50 < or = FEV1 < 80%
      predicted; 14%, 30 < or = FEV1 < 50% predicted; 1%, FEV1 < 30% predicted.
      Patients with mild to moderate airflow limitation rarely consulted the pulmonary
      medicine department. The prevalence of airflow limitation was more frequent among
      in- and out-patients than in the random sample population. Spirometry prior to
      surgical operation is useful for the early detection of COPD and these data could
      be an important source for medical staff seeking a definitive diagnosis of
      patients revealing airflow limitation.

PMID- 15478621
TI  - [Brain natriuretic peptide].
AB  - Plasma levels of various neurohumoral factors are activated and have an important
      role of the pathophysiology of congestive heart failure (CHF). Atrial natriuretic
      peptide (ANP) and brain (or B-type) natriuretic peptide (BNP) are secreted from
      cardiomyocytes in response to atrial or ventricular wall stretch. The natriuretic
      peptides have a fundamental role in cardiovascular remodeling, volume
      homeostasis, and the response to myocardial injury. Clinical investigations of
      these peptides have focused on their diagnostic usefulness for heart failure and
      left ventricular dysfunction and their prognostic usefulness after acute coronary
      syndromes and heart failure. In patients with left ventricular systolic
      dysfunction, a high plasma BNP level is an independent prognostic predictor of
      CHF patients, suggesting that the compensatory activity of the cardiac
      natriuretic peptide system is attenuated as mortality increases in chronic CHF
      patients with high plasma levels of ANP and BNP. BNP is more useful than ANP for
      diagnosis and management of CHF. Recently, rapid BNP assay is available in our
      country, rapid measurement of BNP in the emergency department may improve the
      evaluation and treatment of patients with acute dyspnea and thereby reduced the
      time to discharge and the total cost of treatment. In addition, BNP-guided
      treatment of heart failure may reduce total cardiovascular events, and delayed
      time to first event combination with intensive clinically guided treatment.

PMID- 15478622
TI  - [Pulse wave velocity].
AB  - Pulse wave velocity (PWV) reflects arterial stiffness. PWV correlates with other
      markers reflecting the severity of atherosclerosis such as the findings of
      ultrasound examination of carotid artery. In addition, several studies
      demonstrated that increased PWV is a predictor of future cardiovascular events in
      patients with either hypertension or diabetes mellitus. Thus, PWV is thought to
      be applicable as a marker relating with the severity of atherosclerosis and/or
      predicting future atherosclerotic cardiovascular events. Age and blood pressure
      is a major determinant of PWV, and the influence of these factors should be taken
      into account to use PWV as a marker of cardiovascular risk. On the other hand,
      while anti-hypertensive medication or statins improve PWV, it has not been fully
      evaluated whether these improvement reflect the improvement of prognosis.
      Therefore, the significance of PWV as a surrogate marker for the treatment of
      atherosclerotic cardiovascular risk has not been fully established. Carotid
      femoral PWV is used as a conventional method. Recently, more simple method:
      brachial-ankle PWV is available in clinical settings. This method is simple fully
      enough to apply in a large population. However, brachial-ankle PWV includes
      peripheral component of artery in its assessment of arterial stiffness, and it
      has not been fully concluded that brachial-ankle PWV has a similar potential as a
      marker using the management of atherosclerotic cardiovascular disease as carotid
      femoral PWV. Further study is proposal to evaluate the clinical significance of
      brachial-ankle PWC as a tool using the management of cardiovascular disease.

PMID- 15478623
TI  - [Measurement of pulse wave "augmentation index (AI) "and its clinical
      application].
AB  - Hypertension, hyperlipidemia, diabetes mellitus and obesity, all of these life
      style related diseases advance arteriosclerosis and cause a cardiovascular event.
      It is said that the event can be greatly reduced by improvement of lifestyle or
      medication. The device is recently developed that enables us easily to measure AI
      i.e. augmentation index, and the studies applying the device have been clarifying
      the clinical usefulness of the index. The reflected wave from the peripheral
      artery is superimposed on the ejection wave generated by cardiac contraction,
      although the blood pressure waveform is observed as the synthesized one of those
      two. AI is defined as the proportion of the amplitude of the reflected wave to
      that of the ejection wave, and it does not only express a cardiac load, but also
      arterial stiffness. The vessel with arteriosclerosis generates a large reflected
      wave, and it reaches the left ventricle at high speed. Thereby the heart receives
      large mechanical stress which may cause cardiac hypertrophy, and as a result, the
      sustained stress may cause a serious accident. Thus, it is the management for
      both situations of the heart and the artery that matters, and AI can be regarded
      as a new marker of cardiovascular disease for suitable clinical management on
      both heart and artery.

PMID- 15478625
TI  - [Serotonin: a novel marker for atherosclerotic vascular disease].
AB  - Serotonin is released from nerve terminals distributed at the intestinal
      chromaffin cells, which are taken up into platelets. The serotonin is released at
      the site where platelets are activated in such situations as atherosclerotic
      vascular lesions. Therefore, we assumed that the serotonin level could be a
      suitable marker for atherosclerosis. We developed a new high-performance liquid
      chromatographic (HPLC) method, including a column-switching system and a post
      column reaction with benzylamine, for measurement of serotonin levels in samples
      from patients with coronary heart disease. The vacuum tubes containing the 3mg/ml
      (7.4mmol/l) of ethylenediaminetetraacetic acid dipotassium (EDTA2K) were used for
      collecting the samples of platelet-poor plasma (PPP) because the concentration of
      anticoagulant in the commercially available vacuum tube containing the 1-2mg/ml
      (2.5-5.0mmol/l) of EDTA2K was not enough. The serotonin levels in PPP and whole
      blood of healthy subjects and 4 groups of patients with effort angina pectoris (e
      AP), unstable angina (u-AP), old myocardial infarction (OMI), and vasospstic
      angina pectoris (VSAP), were determined by using the developed method. The
      serotonin levels in PPP from patients of u-AP, OMI, and VSAP were significantly
      higher than those of healthy subjects(p<0.001, p<0.005, and p<0.001). The ratio
      of PPP to whole blood of all disease groups were significantly higher than those
      of healthy subjects (p<0.001). From these findings, we propose that serotonin is
      useful as a novel marker for atherosclerotic vascular disease.

PMID- 15478624
TI  - [Inflammatory markers and cytokines in cardiovascular disease].
AB  - Inflammatory processes play a pivotal role in the pathogenesis of atherosclerosis
      and mediate the stages of atheroma development from initial leukocyte recruitment
      to eventual rupture of the unstable atherosclerotic plaque. Recent investigations
      demonstrated that several inflammatory markers are considered as new predictable
      risk factors for atherosclerosis and cardiac events. Among these markers, C
      reactive protein (CRP) has been most widely studied. CRP is produced in the liver
      in response to interleukin-6 (IL-6), it is an acute phase reactant and used as a
      general inflammatory marker. High-sensitivity-CRP (hs-CRP) which could detect a
      small amount of CRP was recently developed, and numerous large-scale, prospective
      studies have found that elevated baseline levels of hs-CRP are independent
      predictor of cardiovascular events. Inflammatory cytokines such as IL-6 and tumor
      necrosis factor-alpha (TNF-alpha) have also been evaluated as potential tools for
      prediction of the cardiovascular events. In this review, we focused on the recent
      reports and potential use of the inflammatory markers and cytokines as a
      predictable tool for the cardiovascular events.

PMID- 15478626
TI  - [Aldosterone].
AB  - Aldosterone is one the representative cardiovascular hormones involved in the
      blood pressure and body-fluid homeostasis. Elevation of aldosterone leads to
      systemic hypertension through its action on the mineralocorticoid receptor (MR)
      in the kidney. More recent studies demonstrated that aldosterone may produce
      target organ damage through its direct actions on the non-epithelial MR of the
      heart in addition to its systemic effects. Clinical experience in primary
      aldosteronism supports the concept that aldosterone is a risk factor of
      cardiovascular complications, since concentric type of cardiac hypertrophy is
      most common in primary aldosteronism among various types of endocrine
      hypertension. Clinical mega-trial in congestive heart failure (RALES study,
      EPHESUS study) demonstrated blocking angiotensin II action is not sufficient for
      cardioprotection unless aldosterone action is equally blocked. An important
      phenomenon related to this issue is the aldosterone breakthrough which implies a
      reelevation of plasma aldosterone during chronic administration of ACE inhibitors
      and Angiotensin receptor antagonists. Normal level of aldosterone could still be
      a risk factor. Combination of ACE inhibitor or ARB with aldosterone antagonist
      could result in a better cardioprotection in cardiovascular diseases. Although
      spironolactone has been the only one aldosterone antagonist, a new antagonist
      eplerenone has been developed. Eplerenone is specific to MR and is practically
      devoid of the major side effect gynecomastia of spironolactone. Another topic of
      aldosterone is its very quick cardiovascular effect presumably via a non-genomic
      action. All these recent findings support that this adrenocortical steroid
      hormone is as important as angiotensin II. Determining aldosterone levels is
      therefore much morel important than before in the diagnosis and treatment of
      cardiovascular diseases.

PMID- 15478627
TI  - [Neuroanatomy and neurophysiology in schizophrenia].
AB  - Advances in neuroimaging and neurophysiological techniques have enabled detailed
      investigations of the brain pathophysiology of schizophrenia. In this article, we
      first overviewed neuroanatomical and neurophysiological studies of the superior
      temporal gyrus and anterior cingulate cortex in patients with schizophrenia,
      using structural magnetic resonance imaging (s-MRI), MR spectroscopy (MRS), event
      related potentials (ERPs) and magnetoencephalography (MEG). Next, we discussed
      several key points for future research in psychiatric neuroimaging, such as
      disease specificity, heterogeneity, utility as endophenotype markers,
      relationship to psychosocial outcome, and application to clinical purposes.
      Finally, we described important issues, in terms of the infrastructure and
      system, which need to be improved in clinical psychiatry research in Japan.

PMID- 15478628
TI  - [A clinical study of hypochondriac symptoms in patients with depression].
AB  - In this study, the authors investigated the features of depression associated
      with hypochondriac symptoms. The subjects were inpatients of the psychiatry
      clinic of Jichi Medical School who were clinical diagnosed with depression and
      enrolled in the study between June 1, 1997, and June 30, 1999. Of 86 subjects
      enrolled, 49 exhibited hypochondriac symptoms ("hypochondriac group"). Patients
      in the hypochondriac group tended to be older at diagnosis and admission than
      those in the "non-hypochondriac group". Our findings suggested that symptoms of
      both hypochondriasis and depression are related to situational, psychological and
      organizational factors. As many patients consulted health professionals in
      specialties other than psychiatry, we emphasize that primary-care doctors need to
      keep the possibility of depression in mind when examining patients. The frequency
      of delusions associated with depression was higher in the hypochondriac group
      than in the non-hypochondriac group. We therefore suggest that hypochondriac
      attitudes are related to the three major diagnostic features in depressive
      delusions. Many hypochondriac subjects complained of constipation and pain as
      concrete symptoms, but the sites of hypochondriac symptoms showed considerable
      variation. In terms of symptoms of pain, however, affected sites were more
      localized, with many patients reporting headache or lumbago.

PMID- 15478629
TI  - [Psychiatric day care, facilities for social rehabilitation, and psychiatric
      clinics].

PMID- 15478630
TI  - [Role of psychiatric clinics in community care of the aged with dementia-
      including the effect of the introduction of the nursing insurance system].

PMID- 15478631
TI  - [Brain imaging of patients with psychiatric diseases].

PMID- 15478632
TI  - [Study on functional MRI of abnormal eye movements associated with
      schizophrenia].

PMID- 15478633
TI  - [Neuropsychological disorders and functional MRI findings related to false
      memory].

PMID- 15478634
TI  - [Evaluation of drug therapy based on the results of imaging].

PMID- 15478635
TI  - [A seemingly close and yet great distance between the clinical scene and clinical
      evidence].

PMID- 15478636
TI  - [Introduction of new anti-psychotic drugs and changes in the clinical practice].

PMID- 15478637
TI  - [Has new antidepressive agents changed the clinical conditions of depressive
      diseases?].

PMID- 15478638
TI  - [The current status and future of drugs to treat Alzheimer disease].

PMID- 15478639
TI  - [Role of psychiatrists in the management of sleep disorders].

PMID- 15478640
TI  - [Psychiatry and chronobiology].

PMID- 15478641
TI  - [Sleep disorder associated with aging and psychiatry--Is there an evidence that
      drug therapy is effective in the treatment of sleep and behavior disorders of
      Alzheimer disease?].

PMID- 15478642
TI  - [Current status and problems associated with studies of the postmortem brain
      obtained from schizophrenic patients].

PMID- 15478644
TI  - [Epidemiological analysis of Salmonella enteritidis isolates using pulsed-field
      gel electrophoresis and bacteriophage typing over the period of April 2000 to
      March 2003 in Gifu Prefecture].
AB  - We examined a total of 151 Salmonella enterica serovar Enteritidis strains
      isolated in Gifu Prefecture during the period from April 2000 to March 2003 by
      using bacteriophage typing and pulsed-field gel electrophoresis (PFGE).
      Bacteriophage typing classified them into twelve phage types (PT) and RDNC
      (reacted but did not conform). The predominant phage type was PT47 (34.4%)
      followed by PT1 (21.9%), PT4 (16.6%) and RDNC (11.3%). XbaI- and BlnI-digested
      PFGE analyses identified 17 and 44 PFGE patterns, respectively, indicating that
      PFGE with BlnI had more discriminating power than that with XbaI. Combination of
      the phage types and PFGE types of BlnI could make 53 subtypes. Some isolates with
      the same phage type were subdivided into different PFGE types, but those with
      PT47 were not. PT47 isolates were derived from sporadic patients with
      gastroenteritis, food poisoning outbreaks and healthy carriers through the years.
      This suggests that PT47 is highly clonal and disseminates over our prefecture.

PMID- 15478643
TI  - [Clinical symptoms of influenza infection in the 2002-2003 season].
AB  - The highest body temperature and clinical symptoms during the influenza infection
      were analyzed on 2,145 patients with influenza, (type A: 1,408cases, type B:
      737cases: confirmed by a rapid diagnosis kit, Capilia FluA, B), and for 670
      patients with a negative response to the rapid diagnosis kit (controls). The
      study was a multi-center study of the 2002-2003 influenza season. The percentages
      of patients with fever over 38 degrees C, 38.5 degrees C and 39 degrees C were
      significantly higher in influenza A than in influenza B or controls (16-64 yrs).
      Over 80% of the patients in all age groups of 0-6 yrs, 7-15 yrs, 16-64 yrs or
      over 64 yrs with influenza A or B had a cough. The percentage of patients with
      cough was significantly higher for patients with influenza A or B than for
      controls under 65 yrs. The percentages of influenza A or B patients with
      rhinorrhea or loss of appetite were significantly higher than in controls under
      65 yrs. The percentage of patients reporting fatigue, headache or myalgia was
      significantly higher for influenza A than for controls of 16-64 yrs. Differences
      in symptoms, including fever, were minimal between influenza A and B patients
      under 16 yrs, and also among influenza A, B and controls in patients over 64 yrs.
      The percentage of patients with cough was not different among the three age
      groups by influenza A or B. However, the percentage of patients with rhinorrhea,
      loss of appetite, vomiting or diarrhea was higher in children under 16 yrs than
      in adults aged 16-64 yrs in influenza A or B. In conclusion, consideration must
      be given to the patient's age and the type of influenza when doing a symptomatic
      diagnosis of influenza. In addition, the use of a rapid diagnosis kit seems
      necessary for the diagnosis of influenza in elderly patients, who may have no
      specific symptoms of influenza.

PMID- 15478645
TI  - Development of RT-multiplex PCR assay for detection of adenovirus and group A and
      C rotaviruses in diarrheal fecal specimens from children in China.
AB  - Rotavirus, adenovirus, norovirus, sapovirus and astrovirus are considered to be
      significant global enteropathogens associated with sporadic cases and outbreaks
      of acute gastroenteritis. Therefore, a rapid and sensitive assay is preferred to
      screen for the presence of these viruses in diarrheal fecal specimens. In a
      previous study, we developed a reverse transcription single-round multiplex
      polymerase chain reaction (RT-smPCR) assay for the simultaneous detection of
      norovirus (genogroup I, genogroup II), sapovirus and astrovirus in fecal
      specimens (Yan et aL, 2003). Recently, we developed another RT multiplex PCR for
      one-step amplification of all subgenera A to F adenoviruses, and group A and C
      rotaviruses. In this study, a total of 207 fecal specimens collected from
      children with acute gastroenteritis between December 2001 and April 2003 in
      Yunnan Province, China were examined for the presence of adenoviruses, and group
      A and C rotaviruses, by RT-multiplex PCR. The detection rate of these three
      viruses was 55.1% (114 out of 207 specimens), among which adenovirus and group A
      and C rotaviruses were identified in 11, 101 and 1 fecal specimen, respectively.
      Furthermore, one specimen was found to be positive for co-infection with
      adenovirus and group A rotavirus. An epidemic of acute gastroenteritis was also
      identified as peaking mainly in October and November. Taken together, our results
      clearly indicate that this novel assay provides a potentially rapid and
      convenient tool for epidemiologic investigation of diarrhea caused by adenovirus
      and group A and C rotaviruses.

PMID- 15478646
TI  - [Distribution of Legionella spp. in hot spring baths in Japan].
AB  - We investigated the inhabitation of Legionella spp. in hot spring water in
      various regions in Japan. The following results were obtained. 1) Of 710 hot
      spring water samples nationwide, Legionella spp. was isolated from 204 samples
      (28.7%), covering all 47 prefectures. By region, the isolation rate was the
      highest at 31.0% in the Chugoku district, while the isolation rates in Hokkaido,
      Kinki, and Kyushu were low, ranging from 25.0 to 26.2%. The rate in Tohoku,
      Kanto, Chubu, and Shikoku districts was 28.6-30.7%. Regarding the isolation rate
      by pH of hot spring water, the isolation rate was 4.9% at pH 3 or lower, but
      34.8% at pH 3.1-7.5. When pH was 7.6 or higher, the isolation rate was 24.8%. 2)
      Most frequently, the number of bacteria detected was below 10(2) CFU/100ml (98
      samples, 48.0%). The count was between 10(2) and 10(3) CFU/100ml in 71 samples
      (34.8%), and between 10(3) and 10(4) CFU/100ml in 29 samples (14.2%). In 6
      samples (2.9%), the count was higher than 10(4) CFU/100 ml. 3) Among the isolates
      identified, L. pneumophila was the predominant species, and particularly,
      serogroups 1 and 5 were frequently isolated. The above findings clarified that
      although the number of the bacteria is low, Legionella spp. inhabits hot spring
      water throughout Japan.

PMID- 15478647
TI  - [Epidemiological investigation of beta-lactam antibiotic induced vancomycin
      resistant MRSA from clinical isolated MRSA--comparison of detection rate of BIVR
      with or without CZX].
AB  - Recently, beta-lactam antibiotic induced vancomycin-resistant MRSA (BIVR) has
      been reported increasingly in Japan. Between 1998 and 2002, we tried to detect
      BIVR from 500 strains of MRSA in a cancer hospital. And the difference of the
      detection rate under condition of pre-culture with or without ceftizoxime was
      compared. The detection rate of BIVR under condition of pre-culture with 1.0 mg/L
      of ceftizoxime was 20.4% (102/500), and without ceftizoxime was 9% (45/500). That
      of preculture with 1.0 mg/L of ceftizoxime was higher than those without
      ceftizoxime with the significant difference. (p < 0.001; McNemar-t examination).
      In comparing each department, the detection rate of BIVR from Chemotherapy, Head
      & Neck, and Urology department was 33.3%, 27.0%, and 20.0%, respectively. These
      results mean that addition of beta-lactam as ceftizoxime in pre-culture induces
      the ability of resistance to vancomycin for MRSA having a capacity as BIVR.

PMID- 15478648
TI  - [Molecular imaging of transgene expression in brain tumors].

PMID- 15478649
TI  - [Cancer stem cells in pediatric brain tumors].
AB  - Cancers are formed by heterogeneous cell types from immature highly proliferative
      cells to lineage-committed differentiated cells. Transplantation studies have
      suggested the existence of "cancer stem cells", individual cells capable of
      producing an entire tumor. Recent advances in stem cell research have allowed for
      the demonstration of the existence of cancer stem cells in acute myeloid
      leukemia, breast cancer, and, most recently, in pediatric brain tumors. Each of
      these has some similarities with the normal stem cells in the corresponding
      organs. For example, leukemia stem cells express some, but not all, markers of
      hematopoietic stem cells. Regarding pediatric brain tumors, putative cancer stem
      cells were identified from medulloblastoma and also from glioma. These tumor
      derived cells self-renew under clonal conditions, and differentiate into neurons
      and glia as well as into abnormal cells with mixed phenotypes. Interestingly, the
      tumor stem/progenitors, enriched in culture, maintained proliferation after 4
      weeks from transplantation into neonatal rat brain. In this review, we discuss
      the difference as well as the similarity between tumor and normal stem cells, and
      also the possible clinical implication of cancer stem cells.

PMID- 15478650
TI  - [Clinical analysis of cervical-spine and spinal-cord-injured patients brought in
      without cervical spinal immobilization].
AB  - The purpose of this study was to determine the incidence of mismanaged injury of
      the cervical spinal cord, to identify factors contributing to a failure to
      recognize such injury. Thirty-three patients with cervical spinal cord injury
      were transported to emergency department during the period from October, 1999 to
      March, 2001. Seven patients (21%) of them were transferred without cervical spine
      immobilization. Mechanism of injury in 7 patients was fall in 4, motor vehicle
      crash in 2, unknown in one. Clinical signs on admission revealed neck pain and/or
      back pain in 4 patients, altered mental status in 4 patients, numbness of
      extremities in 2 patients, paradoxical respiration in 2 patients, respiratory
      arrest in one. Neurological classification of Frankel grade was A in 2, B in 1, C
      in 2, D in 1 and E in 1. All trauma patients with a cervical spine injury or with
      a mechanism of injury having the potential to cause cervical spine injury should
      be immobilized at the scene, during transport and at the emergency room by using
      one of several available methods.

PMID- 15478651
TI  - [Multiple chronic subdural hematoma in shaken-baby syndrome].
AB  - We described a case of shaken-baby syndrome with multiple chronic subdural
      hematomas. A 10-month-old male baby was admitted to our hospital because of loss
      of consciousness and convulsions. CT scan revealed an acute subarachnoid
      hemorrhage extending into the interhemispheric fissure and supracerebellar space.
      The patient was treated conservatively, and discharged from the hospitaL Two
      months after ictus, a baby was admitted to our hospital with general fatigue. CT
      scan demonstrated multiple chronic subdural hematomas. Burr hole irrigation and
      drainage brought about complete disappearance of these lesions. Retrospectively,
      it was found that these multiple subdural hematomas were due to shaken-baby
      syndrome. Shaken-baby syndrome is a form of child abuse that can cause
      significant head injury, and subdural hematoma is the most common manifestation.
      It is well known that the outcome of shaken-baby syndrome is generally not good.
      It is important to suspect shaken-baby syndrome when a chronic subdural hematoma
      is seen in a baby.

PMID- 15478652
TI  - [Adenoid cystic carcinoma with striking intracranial extension: a case report].
AB  - We report a case of intracranial adenoid cystic carcinoma in the middle cranial
      fossa. A 40-year-old woman had noticed a tumor in the left external auditory
      canal 8 years previously. It was totally resected at that time. Histologically,
      the tumor was diagnosed as an adenoid cystic carcinoma. Recently the patient
      presented with loss of consciousness, suffering from mild recent-memory
      disturbance. Neurological examination revealed no other abnormalities. Magnetic
      resonance imaging (MRI) demonstrated an enhanced solid mass with a multicystic
      component in the left temporal lobe. She underwent subtotal removal of the tumor.
      It was well-demarcated, and was confirmed to be adhesive to the dura matter of
      the middle cranial fossa. Histology of the tumor was the same as it was 8 years
      ago. She was discharged from our hospital without neurological deficits. Two
      months after surgery, gamma knife radiosurgery was performed against the residual
      tumor.

PMID- 15478653
TI  - [Usefulness of FDG-PET in monitoring effects of the modality therapy for central
      nervous system malignant lymphoma: report of three cases].
AB  - We have reported three cases of central nervous system malignant lymphoma in
      which FDG-PET was useful in monitoring therapeutic effects. Case 1: A 53-year-old
      man complained of gait and memory disturbance. An MRI of the patient's brain
      showed enhanced mass lesions in the bifrontal lobe. An FDG-PET showed markedly
      high uptake of the tracer, which means a higher metabolism of glucose. The tumor
      was biopsied and the histological diagnosis was diffuse B cell lymphoma. The
      patient received chemotherapy and external irradiation therapy. Case 2: A 64-year
      old woman suffered memory disturbance and left hemiparesis. An MRI showed a right
      frontal mass lesion, and FDG-PET showed high uptake of glucose. After the
      histological diagnosis was determined as diffuse large B cell lymphoma, the
      patient received the same therapy as case 1. Case 3: A 55-year-old woman suffered
      right hemianopsia. An MRI showed an enhanced lesion in the right basal ganglia
      and an FDG-PET showed high uptake of glucose. After the histological diagnosis
      was determined as diffuse large B cell lymphoma, the patient received the same
      therapy as case 1 and 2. In all cases, high uptake of glucose disappeared on the
      PET after initial chemotherapy, although an enhanced lesion continued on MRI even
      after radiation. FDG-PET was useful in monitoring the therapeutic effects of
      malignant lymphoma. These results indicate that we were able to confirm the
      effectiveness of the therapy in the early stage.

PMID- 15478654
TI  - [Ruptured aneurysm arising from the anterior medullary segment of the posterior
      inferior cerebellar artery: report of two cases].
AB  - In the distal posterior inferior cerebellar artery (PICA), saccular aneurysms
      originating at the first proximal segment, anterior medullary segment (AMS), are
      unusual but important due to the presence of critical perforators that branch off
      the PICA and supply the lower brainstem. Because the anatomy of the PICA varies,
      no standard treatment strategy has been agreed upon to date. We successfully
      treated 2 patients with open surgery. One was a 53-year-old man who presented
      with Hunt-Hess grade 2 subarachnoid hemorrhage (SAH). Cerebral angiography
      revealed an irregular fusiform AMS aneurysm extending to the lateral medullary
      segment. Intraoperative inspection showed some perforators to the brain stem
      branching from just proximal and distal to the aneurysm. The patient underwent
      aneurysmal trapping and occipital artery-PICA anastomosis to preserve perforators
      flow, and was discharged without any neurological deficits. Another patient, a 74
      year-old woman, was transferred to our institute because she suddenly became
      comatose. She was found to have a ruptured saccular AMS aneurysm. On the 15th day
      after the event, she underwent successful aneurysmal clipping preserving
      perforators by surgical inspection. As both patients manifested intra-aneurysmal
      thrombosis, we suggest that patients presenting with AMS aneurysms that display
      unusual features require careful management and judicious choice of treatment.
      Based on our experience we suggest that direct surgery, which facilitates the
      identification of perforators and allows for revascularization, is the
      appropriate treatment choice in patients who present with this entity.

PMID- 15478655
TI  - [Cerebral aneurysms in identical twins].
AB  - The hypothesis that genetic factors play a role in the genesis of cerebral
      aneurysms may be supported by clinical analysis of cerebral aneurysms in
      identical twins. In addition to reporting the present case, we review the
      literature on clinical features and genetical considerations in this matter. A
      forty-two-year-old male presented with subarachnoid hemorrhage (SAH) due to a
      left MCA aneurysm. At the age of 39, his identical twin brother also had SAH due
      to a ruptured left MCA aneurysm. This identical twin brother and his father's
      sisters died of SAH. Venous blood of the patient and his parents was collected to
      determine apolipoprotein E, angiotensinogen, angiotensin-converting enzyme, and
      very low density lipoprotein receptor genes. This analysis suggested a strong
      genetic association of apolipoprotein E epsilon4 with the pathogenesis. Including
      our cases, 13 cases of cerebral aneurysms in identical twins have been reported.
      There was a total of 37 aneurysms. Six twins had the same sites of aneurysm.
      These aneurysms show a tendency to be small in size, and to cause a high
      frequency of SAH occurring at a similar age. In young adults, cerebral aneurysms
      in identical twins tend to rupture. A screening diagnosis should be carried out
      as early as possible on an asymptomatic twin when the other has been discovered
      to have a ruptured cerebral aneurysm. Preventive treatment and systemic genome
      wide linkage study should be conducted.

PMID- 15478656
TI  - [Deep brain stimulation of the subthalamic nucleus in patient with Parkinson's
      disease].

PMID- 15478657
TI  - [Metastatic skull tumor, epidermoid cyst, dermoid cyst, and intraosseous
      meningioma].

PMID- 15478658
TI  - [Recent developments in study of functional gastrointestinal disorders].

PMID- 15478659
TI  - [Present status and prospects of wireless capsule endoscopy].

PMID- 15478660
TI  - [Clinical value of enteroscopic examinations using the double-balloon endoscope].

PMID- 15478661
TI  - [Case of esophageal early cancer concomitant with vigorous achalasia].

PMID- 15478662
TI  - [Case of ulcerative colitis induced by mesalazine with acute aggravated colitis
      like symptoms].

PMID- 15478663
TI  - [Case of multiseptate gallbladder].

PMID- 15478664
TI  - [Case report on paraganglioma of the mesenterium].

PMID- 15478665
TI  - [Two young adult cases of superior mesenteric vein thrombosis].

PMID- 15478666
TI  - [Influence of Helicobacter pylori infection on iron accumulation in hepatitis C].

PMID- 15478667
TI  - [Case of 25-year-old man with severe anemia and abdominal pain].

PMID- 15478668
TI  - Family caregiver burden in the context of the long-term care insurance system.
AB  - This paper covers our recent work regarding family caregiver burden for elderly.
      The topics are as follows: cross-sectional studies on caregiver burden; changes
      in caregiver burden; appropriateness of the Long-Term Care insurance assessment
      scheme; attitude towards caregiving among caregivers; and the development of the
      short version of the Japanese version of the Zarit Caregiver Burden Interview.

PMID- 15478669
TI  - Oral health conditions in patients with Parkinson's disease.
AB  - BACKGROUND: Oral health conditions and related factors of patients with
      Parkinson's disease (PD) have not been well elucidated. The aim of the present
      study was to investigate oral health conditions and related factors which may
      influence oral health conditions among patients with PD. METHODS: We compared
      oral health conditions and related factors between 104 PD patients and 191
      inhibitants (controls) who received dental health check-ups in Hokkiado, Japan.
      The unconditional logistic regression model was used for adjusting for sex and
      age. We also conducted stratified analysis by sex and age group using this model.
      The chi2 test and the Cochran-Mantel-Haenzel test were used for simple and
      stratified analyses of knowledge of oral health among PD patients, respectively.
      RESULTS: In the present survey, we found the following results. (1) PD patients
      had more complaints of chewing difficulties and denture discomfort than controls.
      (2) Fewer PD patients had their own teeth than controls regardless of sex. (3)
      Fewer PD patients cleaned their dentures every day than controls, regardless of
      sex or age. (4) More than half of the PD patients had problems with swallowing.
      CONCLUSION: We found that PD patients had more complaints about their oral health
      and more problems in oral health behavior than the general population. These
      findings may provide useful information for the caregivers of PD patients to
      conduct oral health care as well as for making oral health plans for PD patients
      and for medical and welfare services.

PMID- 15478670
TI  - Physical growth charts from birth to six years of age in Japanese twins.
AB  - BACKGROUND: The purpose of this study was to analyze the characteristics of the
      physical growth of twins in childhood and to present growth charts of Japanese
      twins. METHODS: The subjects consisted of 2029 pairs of normally developed
      Japanese twins. Growth data were obtained by mailed or hand-distributed
      questionnaires. Factors that affect body weight and height/length at selected
      ages were analyzed by stepwise regression analysis. Selected percentiles of body
      weight, height/length, and body mass index were calculated according to sex, and
      growth curves were drawn using a spline function. The size deficit of the twins
      compared to the standards for the general population of Japan was calculated.
      RESULTS: Gestational age, parity, zygosity, and birth order affected physical
      growth in varying degrees, although the overall effects themselves were small and
      mostly disappeared by one year of age. Growth charts of the twins present growth
      at selected percentiles from birth to 6 years of age according to sex. The size
      deficit of the twins was largest at birth: more than 20% for weight and
      approximately 6% for length compared to the 50th percentile of the standard for
      the general population of Japan. These deficits decreased rapidly in the first 6
      to 12 months, and were found to be as low as 0-2% at 4 to 6 years of age.
      CONCLUSION: Growth charts specifically for twins are needed, at least for the
      first 1 to 3 years of age but not beyond the age of 6 years.

PMID- 15478671
TI  - Anthropometric, lifestyle and biomarker assessment of Japanese non-professional
      ultra-marathon runners.
AB  - BACKGROUND: Anthropometric characteristics, lifestyle, and baseline biological
      markers of Japanese non-professional ultra-marathon runners have not been fully
      assessed. METHODS: We evaluated anthropometric characteristics, lifestyle, and
      baseline biological markers of 180 Japanese amateur ultra-marathon runners (144
      males [mean age: 50.5 +/- 9.4 (standard deviation) years] and 36 females [48.9 +/
      6.9]), and compared them with those of participants in a community heath check
      up program and with the figures in the literature. We furthermore evaluated
      baseline blood indices according to monthly running distance with analysis of
      variance adjusted for age, body mass index, smoking and alcohol drinking habits.
      RESULTS: The ultra-marathon runners demonstrated more favorable values for body
      mass index and bone density, and the proportion of smoking, and undertaking
      physical activity (for both sexes), eating breakfast (for males), and having
      daily bowel movements (for females), while greater proportion of alcohol drinking
      habit (for both sexes), than the comparison group. Average monthly running
      distances and standard deviations (km) were 257.2 +/- 128.9 for males and 209.0
      +/- 86.2 for females. Male runners possessed beneficial markers, including
      lowered triglyceride and elevated high-density lipoprotein cholesterol, and their
      values showed hockey-stick (or inverse hockey-stick) patterns depending on their
      monthly running distance. Some subjects running more than 300 km/month exhibited
      signs of an over-reaching/training syndrome, including somewhat lowered
      hemoglobin, ferritin and white blood cell count, and elevated creatine kinase and
      lactate dehydrogenase. CONCLUSIONS: Together with a desirable lifestyle, Japanese
      non-professional ultra-marathon runners with vigorous exercise habit demonstrated
      a preferable health status according to biological indices.

PMID- 15478672
TI  - Sleeping habit and other life styles in the prime of life and risk for
      ossification of the posterior longitudinal ligament of the spine (OPLL): a case
      control study in Japan.
AB  - BACKGROUND: Although the average age of onset of ossification of the posterior
      longitudinal ligament of the spine (OPLL) is at around 50 years, the onset of the
      symptoms is insidious and the progression is very slow. The etiology of OPLL has
      not been elucidated in detail. Previous studies have suggested that a high-salt
      diet and low consumption of animal protein, glucose intolerance and high body
      mass are risk factors for OPLL. However, there is little information about the
      relationship between OPLL and life styles in the prime of life (between 30 and 50
      years). METHODS: To facilitate early prediction and prevention of OPLL, we
      analyzed life styles such as sleeping habit, physical exercise, smoking, alcohol
      drinking and hangover in subjects in the prime of life. Self-administered
      questionnaires were obtained from patients with OPLL and their sex- and age
      matched controls. Sixty-nine patients diagnosed with OPLL within 3 years
      previously and 138 sex- and age-matched controls without backbone diseases,
      randomly selected from participants in a health checkup in a local town, were
      enrolled. RESULT: Moderate amount of sleep (6-8 hours vs. 5 hours or shorter and
      9 hours or longer; odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.06,
      0.54) and a regular sleeping habit (i.e., going to bed and getting up at regular
      time) (OR=0.44, 95% CI=0.22, 0.90) were associated with a decreased risk of OPLL
      even after adjusting for other factors. On the other hand, moderate physical
      exercise (once a week or more v.s. less than once a week: OR=0.97, 95% CI=0.42,
      2.26), smoking (OR=1.41, 95% CI=0.67, 2.97), drinking (OR=1.08, 95% CI=0.53,
      2.20) and hangover (OR=1.12, 95% CI=0.43, 2.94) in the prime of life showed no
      correlation with risk of OPLL. CONCLUSION: Good sleeping habits in the prime of
      life may decrease the risk of OPLL.

PMID- 15478673
TI  - Creating a brochure to promote understanding of epidemiologic research.

PMID- 15478674
TI  - Delayed encephalopathy after carbon monoxide intoxication: prognosis is still
      uncertain.

PMID- 15478675
TI  - Muscular dystrophy: from pathogenesis to strategy.
AB  - Muscular dystrophies are a genetically heterogeneous group of degenerative muscle
      disorders. It characterized by progressive muscle wasting and weakness of
      variable distribution and severity. There are several subgroups including
      Duchenne/Becker, fascioscapulohumeral, limb-girdle, oculopharngeal, and
      congenital muscular dystrophy. Diagnosis is dependent to the characteristic
      clinical features in distribution of predominant muscle weakness, disease course
      and age onset as well as variable serum concentration creatine kinase, muscle
      histology, and genetic inheritance. Nearly 30 genes and encoded proteins are
      known to give rise to various forms of muscular dystrophy. Development of new
      prospects therapy for the muscular dystrophies is a big challenge. The target of
      strategies is aimed at inducing of a functional protein and improving the
      function of muscle weakness. These strategies include gene, cell and
      pharmacological therapies. However, efficiency of systemic delivery vectors to
      targets, immune reaction to vector and gene products, and toxicity to vector that
      must be solved before an effective treatment is available.

PMID- 15478676
TI  - Effect of topiramate on intractable seizures in Taiwanese children.
AB  - We performed a prospective study to evaluate the effect of topiramate as an
      adjunctive therapy in Taiwanese children with intractable partial epilepsy and
      generalized epilepsy. Thirty children aged from 2 to 16 years (8.5 +/- 3.8 years)
      were enrolled in this study. Eighteen children (60.0%) had partial epilepsy, and
      12 children (40.0%) had generalized epilepsy. These children were experiencing
      more than one seizure per month even under a stable antiepileptic regimen
      treatment. Topiramate was begun at 1 mg/kg x day, and the dosage was raised by 1
      mg/kg x day each week. Titration continued for 4 weeks or more. The maximal
      dosage was 10 mg/kg x day. In children with partial epilepsy, six children
      (33.3%) achieved > or = 50% frequency reduction, while eight children (44.4%)
      achieved a seizure-free state. In children with generalized epilepsy, including
      infantile spasms, four children (33.3%) achieved > or = 50% frequency reduction,
      while five children (41.7%) achieved a seizure-free state. The most common
      adverse effect was poor appetite (10.0%). No idiosyncratic reactions to
      topiramate were found. Only one patient discontinued topiramate because of
      central hyperventilation. Topiramate can be used as an adjunctive antiepileptic
      drug for intractable epileptic children in Taiwan.

PMID- 15478677
TI  - Delayed encephalopathy after carbon monoxide intoxication--long-term prognosis
      and correlation of clinical manifestations and neuroimages.
AB  - In order to understand the correlation between the clinical and neuroimaging
      manifestations and the long-term prognosis in delayed encephalopathy after carbon
      monoxide (CO) intoxication, we retrospectively reviewed 12 patients who had
      delayed encephalopathy from 89 patients with CO intoxication. There were 8 men
      and 4 women, with a mean age of 54.4 +/- 17.2 years (range: 11-79 years). All
      patients had prominent consciousness disturbance in the acute stage and received
      high flow of O2 or hyperbaric oxygen therapy. All of them regained consciousness
      within 1-7 days, but subsequently developed delayed encephalopathy. The delayed
      encephalopathy occurred from 14 to 45 days after recovery from the acute stage.
      The clinical manifestations included cognitive impairment, akinetic mutism,
      sphincter incontinence, gait ataxia and extrapyramidal syndromes such as chorea,
      dystonia, and parkinsonism. Brain MRI revealed multiple lesions in the
      subcortical white matter and basal ganglia, mostly in the globus pallidus, and to
      a lesser degree in the putamen, and caudate. In the follow-up period, sphincter
      incontinence first disappeared. The cognitive impairment improved greatly in the
      following few months, but the involuntary movements were improved only slightly.
      Some patients had persistent neurological sequelae, such as dystonia. Similary,
      the follow-up brain MRI showed a steady improvement. In conclusion, the delayed
      encephalopathy usually developed 2 weeks to 1.5 months after the acute phase of
      CO intoxication. Globus pallidus and subcortical white matter were commonly
      involved. The neurological manifestations improved and correlated roughly with
      the neuroimaging changes.

PMID- 15478678
TI  - The finding and evaluation of EMG-guided BOTOX injection in cervical dystonia.
AB  - In this prospective study we report the results of EMG-guided BOTOX injections in
      a total of 15 cervical dystonia (CD) patients. Pre-treatment and post-treatment
      evaluations included physical examination results, Tsui ratings, and video
      recording. The dosage of BOTOX injection was determined by the EMG pattern, type
      of CD, and the degree of muscle hypertrophy. Seven patients underwent injections
      with and without EMG, and eight patients underwent injections with EMG-guidance
      only. The results showed that among the patients who underwent EMG-guided BOTOX
      injection there are: (1) fewer BOTOX-related side effects due to injection of the
      adequate dose of BOTOX to the accurate site of hyperactive muscles, (2) greater
      clinical improvement due to confirmation of hyperactivity in muscles in each type
      of cervical dystonia, (3) a better ability to reduce the amount of oral
      medication for treatment of muscle pain and spasms. We suggest that the use of
      EMG-guided BOTOX injections be considered for those CD patients with retrocollis,
      those who have had a sub-optimal treatment response to non EMG-guided BOTOX
      injections, and those with increased concern of side effects or a concomitant
      goal of reducing oral medications.

PMID- 15478679
TI  - Sequential appearance and disappearance of hemianopia, palinopsia and
      metamorphopsia: a case report and literature review.
AB  - We report a case with a sequential appearance and disappearance of homonymous
      hemianopsia, palinopsia and metamorphopsia in the defective visual field within
      two days. She had a stroke nine months ago and recovered completely. During that
      episode, dizziness and unsteadiness happened suddenly and was followed by above
      mentioned visual symptoms. Brain image and blood perfusion studies showed an old
      right occipital lesion with hemodynamic changes. Electroencephalograms performed
      immediately just after the disappearance of all the above-mentioned symptoms
      subsided and four months later showed similar findings, some isolated independent
      sharp waves over bilateral temporal areas, with right posterior extension. These
      were independent of her visual symptoms. The pathophysiologies of our case could
      be a sequential hemodynamic change in the right occipital area, from
      hypoperfusion to transient hyperperfusion and finally to normal perfusion.
      Potential mechanisms are discussed with literature review.

PMID- 15478680
TI  - Low back pain in a pregnant woman.
AB  - Low back pain is very common and often considered a part of normal pregnancy.
      Because the pain is always attributed to pregnancy, referral to a specialist is
      often delayed. We describe a young woman who developed low back pain and signs of
      progressive spinal cord compression at 33 weeks' gestation of her second
      pregnancy. Magnetic resonance imaging of the thoracic spine showed a collapsed
      T11 vertebral body and a large paraspinal and intraspinal tumor compressing on
      the spinal cord from the right. Emergent surgical decompression and removal of
      the tumor mass was done. Pathological examination revealed metastatic
      adenocarcinoma and subsequently, a palpable nodule was found in the left breast,
      which, on biopsy, proved to be an invasive lobular carcinoma.

PMID- 15478681
TI  - [Neuropharmacoeconomics].
AB  - Pharmacoeconomics is concerned with how to allocate drug resources among
      alternative uses efficiently and effectively. Economic evaluation is a set of
      formal quantitative methods to capture the outcomes and costs of alternate
      intervention strategies. There are four basic types of economic evaluations used
      to assess interventions, are classified on the basis of the outcomes employed: 1.
      Cost minimization (CMA) is the comparison of costs of alternative interventions
      when the outcomes are assumed to be equal or similar, and the control
      intervention has been established. 2. Cost-effectiveness (CEA) is appropriate
      when the health outcomes are measured in common physical units, such as death or
      disability, or years gained or increased function, or points on cognitive scales.
      3. Cost utility (CUA) is an extension of cost-effectiveness, where different
      types of health outcomes are weighted according to assigned values of 'quality of
      life' to produce a composite of both the physical measurement and the value
      assigned to it, e.g. quality-adjusted life years (QALY) or disability-adjusted
      life years (DALY). A common denominator measure of effectiveness is thus the life
      years of expected survival, or the QALY. The global burden disease (GBD)
      researchers adopted an internationally standardized form of the QALY, which they
      called the DALY. A quality of life measure can be translated into a scale that
      ranges from a low of 0.0 (the worst possible health state, usually taken as
      death) to 1.0 (perfect health). The purpose is to make explicit the measurement
      of costs and value assigned to benefits. 4. Cost-benefit (CBA) analysis value
      health outcomes in monetary terms, often based on the concept of 'willingness to
      pay'. The common drugs used by the neurologists had been discussed in this
      article based on the point view of pharmacoeconomics.

PMID- 15478682
TI  - Skin biopsy in cerebral autosomal dominant arteriopathy with subcortical infarct
      and leukoencephalopathy.

PMID- 15478683
TI  - [A thought on being good neurologists].

PMID- 15478684
TI  - Nutrients for cognitive development in school-aged children.
AB  - This review considers the research to date on the role of nutrition in cognitive
      development in children, with a particular emphasis on the relatively neglected
      post-infancy period. Undernutrition and deficiencies of iodine, iron, and folate
      are all important for the development of the brain and the emergent cognitive
      functions, and there is some evidence to suggest that zinc, vitamin B12, and
      omega-3 polyunsaturated fatty acids may also be important. Considerations for
      future research include a focus on the interactions between micronutrients and
      macronutrients that might be influential in the optimization of cognitive
      development; investigation of the impact of nutritional factors in children after
      infancy, with particular emphasis on effects on the developing executive
      functions; and selection of populations that might benefit from nutritional
      interventions, for example, children with nutrient deficiencies or those
      suffering from attention deficit-hyperactivity disorder and dyslexia.

PMID- 15478686
TI  - Genetic manipulation in nutrition, metabolism, and obesity research.
AB  - We summarize the current standard methods for overexpressing, inactivating, or
      manipulating genes, with special focus on nutritional and obesity research. These
      molecular biology procedures can be carried out with the maintenance of the
      genetic information to subsequent generations (transgenic technology) or devised
      to exclusively transfer the genetic material to a given target animal, which
      cannot be transmitted to the future progeny (gene therapy). On the other hand,
      the RNA interference (RNAi) approach allows for the creation of new experimental
      models by transient ablation of gene expression by degrading specific mRNA, which
      can be applied to assess different biological functions and mechanisms. The
      combination of these technologies contributes to the study of the function and
      regulation of different metabolism- and obesity-related genes as well as the
      identification of new pharmacologic targets for nutritional and therapeutic
      approaches.

PMID- 15478687
TI  - Consensus Conference on Nasal Polyposis.

PMID- 15478688
TI  - Help is on the way: JNE's new feature, Syllabus Selections.

PMID- 15478685
TI  - Research issues in genetic testing of adolescents for obesity.
AB  - Obesity is often established in adolescence, and advances are being made in
      identifying its genetic underpinnings. We examine issues related to the eventual
      likelihood of genetic tests for obesity targeted to adolescents: family
      involvement; comprehension of the test's meaning; how knowledge of genetic status
      may affect psychological adaptation; minors' ability to control events;
      parental/child autonomy; ability to make informed medical decisions; self-esteem;
      unclear distinctions between early/late onset for this condition; and social
      stigmatization. The public health arena will be important in educating families
      about possible future genetic tests for obesity.

PMID- 15478689
TI  - Leaving the safe harbor of competency-based and outcomes education: re-thinking
      practice education.

PMID- 15478690
TI  - Eleven tips for the new college teacher.
AB  - New faculty members who may have many years of clinical experience often feel
      unprepared for the classroom setting. While classes on pedagogy provide many
      important concepts for teaching, some practical points may be missed. This
      article offers 11 strategies to make the transition from clinical nursing
      practice to academia easier, and the teaching role more effective.

PMID- 15478691
TI  - An action research on the development of a caring curriculum in Taiwan.
AB  - The purpose of this study was to plan, develop, implement, and evaluate the
      effectiveness of the first-year course of a 5-year nursing caring curriculum. An
      action research method involving participant observation investigated how 18
      instructors in a junior college nursing program implemented caring in the course.
      Data gathered through observation, interviews, and questionnaires were used for
      evaluation and revision of the course. Results included development of the
      framework for the caring curriculum and the contents of the first-year course,
      Introduction to Caring. Course content included the concepts of caring ("love and
      sincerity," "caring communication," "empathy and respect," "acceptance and
      trust," and "offering of self"), performance of caring actions ("care of self,"
      "care of family members," and "care of peers"), and caring motivations ("caring
      reinforcing factors" and "caring restraining factors"). Teaching strategies
      included role modeling, dialogue, reflection, journaling, and caring groups.
      Evaluation showed that student caring knowledge, attitudes, and behavior improved
      after course implementation.

PMID- 15478692
TI  - Complementary and alternative therapies in nursing curricula: a new direction for
      nurse educators.
AB  - The scope of nursing practice is expanding to include the use of complementary
      and alternative therapies (CAT). This expansion is occurring because of changes
      in professional and societal attitudes toward the use of such therapies. In this
      article, we discuss the use of CAT and the development of medical and nursing
      educational programs related to these therapies in Eastern and Western societies.
      In addition, we identify future directions for incorporating content on such
      therapies into nursing education programs in the United States. We suggest that
      undergraduate nursing programs need to introduce the philosophy of Oriental
      medicine and content on some of the common therapies and that graduate nursing
      programs that include content on the use of CAT in nursing practice can possibly
      be developed.

PMID- 15478693
TI  - Conceptions of critical thinking held by nurse educators.
AB  - This study investigated nurse educators' conceptions of critical thinking used in
      making judgment related to nursing. Twelve nurse educators from a large nursing
      school in an urban environment in New Zealand participated in this qualitative
      study. A semistructured questionnaire was used to explore the nurse educators'
      conceptions of critical thinking. The study found that the participants viewed
      rational, logical thinking as a central focus of critical thinking. However, in
      addition to these traditional perspectives, the nurse educators also included in
      their conceptions views more commonly held by feminist writers. These aspects
      focused on attention to intuition, subjective knowing, attention to context,
      emotions, and caring.

PMID- 15478694
TI  - Stressors and counseling needs of undergraduate nursing students in Ibadan,
      Nigeria.
AB  - Existing evidence suggests that nursing students have high levels of stress and
      that counseling and other support services should be made available to them.
      However, the stressors and counseling needs of undergraduate nursing students in
      Nigeria have yet to be explored. This study used a questionnaire to investigate
      the stressors, counseling needs, and desired counseling facilities of
      undergraduate nursing students at the University of Ibadan. Common stressors
      included excessive schoolwork, financial problems, inadequate recreational
      facilities, and overcrowded accommodations. There was an association between
      reporting inconsiderate, insensitive lecturers as stressors and evidence of
      psychological distress. Nearly 60% of the respondents felt counseling would help
      them, and most desired counseling for academics, finances, and relationships.
      Most (78%) of the respondents preferred an independent facility with trained
      counselors. Desired characteristics for the services included accessibility,
      affordability, confidentiality, and a friendly atmosphere. Educators and
      administrators should use this information to design counseling facilities for
      students.

PMID- 15478695
TI  - RN to FNP: a qualitative study of role transition.
AB  - Registered nurses who return to school in a nurse practitioner program undergo
      role transition throughout the educational process and into the postgraduate
      period. This study examined the role transition that occurs in family nurse
      practitioner (FNP) students. A descriptive, qualitative design was used with in
      depth telephone interviews of 9 female FNPs who had recently graduated. A
      conceptual model was generated that described the role transition from RN to FNP.
      Two phases of role transition occurred and were depicted by the central
      categories that emerged: extrinsic obstacles, intrinsic obstacles, turbulence,
      positive extrinsic forces, positive intrinsic forces, and role development.
      Although the central categories were found to be the same in Phase I and Phase
      II, the defining characteristics differed. This study has implications for FNPs,
      students, and educators regarding role transition. It presents new findings not
      identified in prior research: personal commitments and sacrifices were identified
      as specific obstacles encountered during the educational process, and differences
      were found between inexperienced and experienced RNs in relation to the FNP role
      transition during the educational period.

PMID- 15478696
TI  - What constitutes advanced assessment?
AB  - As programs to prepare advanced practice nurses for primary care have flourished
      during the past decade, faculty aspire to teach a health assessment course that
      is more than a review of undergraduate work. Therefore, course faculty
      constructed a list of advanced assessment competencies. The purpose of this
      descriptive study was to validate the competencies clinical preceptors' rated as
      important via a mailed survey. Overall, the competencies received high mean
      ratings. The item receiving the highest mean score was "detects and interprets
      abnormalities in rate and rhythm" from the heart body system. Items within the
      gynecological and breast systems received the highest ratings. This study
      suggests a need to help advanced practice nursing students master all advanced
      assessment competencies on the survey.

PMID- 15478697
TI  - Applying new science leadership theory in planning an international nursing
      student practice experience in Nepal.
AB  - Planning an international practice experience for nursing students is a
      challenging, but rewarding, opportunity. Kwantlen University College faculty
      members' experience of planning for 8 Bachelor of Science in Nursing students to
      study abroad was no exception. Faculty members' and students' interest prompted a
      request for a placement in Nepal. The faculty members involved in the planning
      were dedicated to using a process that would enable them to remain true to the
      program philosophy and theoretical underpinnings throughout the entire
      experience, from the planning phase to the follow-up presentation. Using
      Wheatley's theory, the students and faculty members reexamined their personal
      leadership styles to ensure they remained relationship focused, rather than task
      focused. Wheatley maintained that because the potentiality lies in building
      strong relationships, it is important to support the creative power that lies in
      those involved in a project. This article describes new science leadership and
      relates it to the planning phase for the practice experience in Nepal. Then,
      reflections on how the philosophy of the program may have influenced the
      experience are shared. Finally, critical reflection on using this theory in
      nursing education is presented.

PMID- 15478698
TI  - Creating competent and discerning consumers of the nursing research literature.

PMID- 15478699
TI  - The outcome-present state-testing model applied to classroom settings.

PMID- 15478700
TI  - A DASH of prevention.

PMID- 15478701
TI  - A 48-year-old woman with nausea, vomiting, early satiety, and weight loss.

PMID- 15478702
TI  - Atrial fibrillation: When is rate control enough?

PMID- 15478703
TI  - Benign paroxysmal positional vertigo: how to diagnose and quickly treat it.
AB  - Benign paroxysmal positional vertigo, the most common cause of vertigo, can be
      diagnosed and treated with a simple maneuver that can quickly be performed in the
      primary care physician's office. How to diagnose and manage other causes of
      dizziness, including Meniere disease, acute vestibular syndrome, migraine
      associated vertigo, and motion sickness, is also covered in this article.

PMID- 15478704
TI  - Homocysteine: is it a clinically important cardiovascular risk factor?
AB  - Elevated plasma homocysteine is associated with an increased risk of myocardial
      infarction, stroke, and venous thromboembolism. Folic acid and other B vitamins
      lower plasma homocysteine levels, but whether this therapy confers a clinical
      benefit has yet to be determined. Until we know the results of ongoing clinical
      trials of homocysteine-lowering therapy, testing for and treating elevated
      homocysteine is probably justified only in patients with known cardiovascular
      disease or who are at high risk.

PMID- 15478705
TI  - Hypertension treatment in African Americans: physiology is less important than
      sociology.
AB  - African Americans have higher rates of hypertension and its complications than do
      people of other ethnic groups, and they may respond differently to various
      antihypertensive drugs. Social, cultural, and economic barriers to care are
      probably more important than any true physiologic differences between races.

PMID- 15478706
TI  - The DASH diet for high blood pressure: from clinical trial to dinner table.
AB  - Three recent studies show that a diet rich in fruits, vegetables, whole grains,
      and lowfat dairy products and low in fat, refined carbohydrates, and sodium can
      lower blood pressure either alone or in combination with other lifestyle changes.
      These studies have greatly expanded our knowledge of nonpharmacologic
      interventions to prevent and manage hypertension. They also underscore the need
      for diet and lifestyle counseling in the primary care setting.

PMID- 15478707
TI  - Patient information. Ten tips to help you control your high blood pressure.

PMID- 15478708
TI  - A DASH-like diet can decrease cardiovascular risk, but barriers to implementation
      exist.

PMID- 15478710
TI  - Prices reflect drop in PTCA use.

PMID- 15478711
TI  - Suppliers unhappy with market share turn to courts.

PMID- 15478709
TI  - Politics of preference back in style at AHRMM.

PMID- 15478712
TI  - Facility profile. Aged rural hospital moves into the future.

PMID- 15478713
TI  - Sound effects: design and operations solutions to hospital noise.

PMID- 15478714
TI  - Beware the backbone. Ignoring infrastructure can be a costly design mistake.

PMID- 15478715
TI  - Sign language. Wayfinding design requires a team approach.

PMID- 15478716
TI  - Essential elements. Key components and features of cancer centers.

PMID- 15478717
TI  - Chemical reaction. Pest control enters an environmentally friendly era.

PMID- 15478718
TI  - Healthcare quality expert Quint Studer finds the road to organizational success
      follows the path of employees, physicians, and patients.
AB  - When Quint Studer was president of Baptist Hospital, Inc., in Pensacola, FL, he
      oversaw a metamorphosis in which the organization's patient and employee
      satisfaction levels rose to some of the highest rankings in the nation. Now, as
      head of his own company and author of a new book, he's telling other hospitals
      and healthcare systems how they can "hardwire excellence" and be the quality
      organizations they want to be.

PMID- 15478719
TI  - First national survey measures parents' opinions on the quality, content of well
      child visits.
AB  - When it comes to pediatric checkups, parent satisfaction ratings appear to be
      strongly related to the content and quality of the care their children receive.
      However, only 57% of parents reported that their child received a developmental
      assessment screening procedure to detect disabilities that could compromise
      learning, social interactions, and other functions, according to a first-ever
      nationwide pediatric study.

PMID- 15478720
TI  - NCQA adds four new measures to HEDIS 2005.

PMID- 15478721
TI  - Our political voice.

PMID- 15478722
TI  - Violence breeds violence.

PMID- 15478723
TI  - Letter from Europe.

PMID- 15478724
TI  - APVMA's annual report of adverse experiences for veterinary medicines 2003.

PMID- 15478725
TI  - A review of drugs and techniques used for sedation and anaesthesia in captive
      rhinoceros species.
AB  - Captive rhinoceros species are most frequently sedated and/or anaesthetised with
      the potent opioid, etorphine hydrochloride in combination with an alpha-2
      adrenoreceptor agonist or the butyrophenone, azaperone. Carfentanil citrate based
      combinations have also been used to a lesser extent. In recent years butorphanol
      tartrate based combinations have been used with good success to induce
      neuroleptanalgesia. Sedation and anaesthesia are complicated by the large size of
      all rhinoceros species and their sensitivity to potent opioids. Potential
      complications include respiratory depression, hypoxaemia, hypertension, pulmonary
      shunting and ventilation/perfusion mismatch. The pharmacology of the principal
      drugs used for sedating/anaesthetising rhinoceros is reviewed. Techniques for
      sedating/anaesthetising the various species and potential complications
      associated with chemical restraint are discussed.

PMID- 15478726
TI  - Cervical hyperaesthesia in a Maltese Terrier with necrotising
      meningoencephalitis.
AB  - A 15-month-old female neutered Maltese Terrier was presented with a 12 hour
      history of low head carriage, reluctance to move and yelping when picked up.
      Physical examination was unremarkable apart from cervical hyperaesthesia. Twenty
      four hours after initial assessment there was significant clinical deterioration,
      with the dog exhibiting lateral cervical flexion and neurological abnormalities
      consistent with diffuse multifocal cerebral dysfunction. Cerebrospinal fluid
      analysis revealed a marked pleocytosis. Euthanasia was elected and gross necropsy
      findings included swelling of the right frontal cortex and a focal area of
      necrosis in the ventrolateral grey matter of the frontal cortex. Histological
      examination of the brain tissue revealed focal areas of necrosis and generalised
      non-suppurative inflammation consistent with a morphological diagnosis of
      necrotising encephalomyelitis.

PMID- 15478727
TI  - Possible association between chronic laminitis and some biochemical parameters in
      dairy cattle.

PMID- 15478728
TI  - Effect of heel elevation on forelimb conformation in horses.
AB  - OBJECTIVE: To determine the conformational changes in the distal forelimb of
      horses following heel elevation of 15 degrees and greater. An experimental study
      with repeated, within-horse measurements. PROCEDURE: Five clinically normal,
      mixed-breed horses were used to determine distal forelimb conformation following
      heel elevation from 0 to 45 degrees in 15 degree increments. Data were also
      compared to conformation of the limb in a Kimzey splint. Conformation was
      determined using lateral to medial radiographic projections. Conformation
      parameters assessed included measurement of apparent lengths of digital flexor
      tendons from the origin of their accessory ligaments to the points of insertion,
      and the joint angles of the distal limb. RESULTS: For angles of heel elevation
      from 15 to 45 degrees, the degree of joint angulation increased (increasing
      flexion) with heel elevation for the metacarpophalangeal, and proximal and distal
      interphalangeal joints. Conversely, the measured apparent lengths of the digital
      flexor tendons in the distal limb, decreased. CONCLUSION: The data supports the
      practice of elevating the heel (greater than 15 degrees) for conditions in which
      decreased fetlock extension may be desired such as with laceration or injury to
      the digital flexor tendons. Further study is required to determine whether heel
      elevation greater than 15 degrees reduces in vivo digital flexor tendon tension
      and also to ensure that the marked flexion of the distal interphalangeal joint
      with greater heel elevation is not detrimental over a prolonged period that may
      be required for the rehabilitation of flexor tendon injuries in the horse.

PMID- 15478729
TI  - The prevalence of lice on sheep and control practices in South Australia.
AB  - OBJECTIVE: To assess the prevalence of infestations of lice in sheep flocks and
      to survey control practices for lice in South Australia DESIGN: A total of 201
      managers of sheep flocks, 75 chosen randomly from the high rainfall zone (HR), 76
      from the cereal sheep zone (CS) and 50 from the pastoral zone (PA), were surveyed
      by telephone interview. PROCEDURE: Interviews were conducted between May 19 and
      May 25, 1999, according to a set questionnaire. Information was collected on
      presence of lice at last shearing, control practices for lice, factors important
      for gaining good effect from chemical treatments, sources of information on
      control practices and property details. Survey results were analysed by
      agricultural region. RESULTS: The apparent state prevalence of flocks infested
      with lice was 21%, with 13% infested in the HR, 21% in the CS and 25% in the PA.
      Ninety one percent of managers claimed to take precautions to prevent the
      introduction of lice and 91% routinely checked their flocks for lice. Seventy
      eight percent treated their sheep for lice annually and 85% had treated within
      the last 12 months. Of those treating in the last year, 69% had used a backline
      application, 16% had used a shower dip and 17% had used plunge dipping. Only 4%
      of producers used a long wool treatment. Synthetic pyrethroid (SP) based products
      were used by 50% of producers who used backline treatments in the preceding 12
      months, compared to 42% and 8% for insect growth regulator and organophosphorous
      (OP) based products, respectively. Only 34% of managers identified SP-based
      products as having potential resistance problems. Of those producers who used
      shower or plunge dips in the last 12 months, 75% used an OP based product. Rural
      newspapers and magazines were by far the most commonly noted source of
      information for the control of lice on sheep.

PMID- 15478730
TI  - Estimate of the sensitivity of an ELISA used to detect Johne's disease in
      Victorian dairy cattle herds.
AB  - OBJECTIVE: To estimate the sensitivity of the ELISA used in dairy cattle herds
      participating in the Victorian Bovine Johne's Disease Test and Control Program
      (TCP). PROCEDURE: The percentage of ELISA reactors in age and test cohorts was
      estimated from age-specific test data derived from TCP herds with long testing
      histories. Age-distribution data from production-tested herds enabled estimation
      of reactor rates in animals that were culled or died. RESULTS: ELISA
      sensitivities at the first test round in herds achieving five, six and seven
      annual herd tests were 16.1, 14.9 and 13.5% respectively. The ELISA sensitivity
      in 2, 3 and 4-year-old animals at the first test round in herds testing seven
      times was 1.2, 8.9 and 11.6% respectively but remained between 20 and 30% in
      older age-groups. CONCLUSION: The sensitivity of the ELISA is considerably lower
      than previous estimates, probably because previous estimates were predominantly
      measured against faecal culture, which has subsequently been shown to have low
      sensitivity itself, and did not appreciate the long period that appears to
      precede detectable faecal excretion in most animals.

PMID- 15478731
TI  - The effects of reducing the length of canine teeth in sucking pigs by clipping or
      grinding.
AB  - OBJECTIVE: To provide production data that would support or discount current
      teeth clipping practices in sucking pigs. DESIGN: Intervention study of 207
      litters of pigs on a commercial farm. PROCEDURE: Litters were assigned to one of
      three interventions undertaken at 1 day of age: clipped using hand-operated side
      cutter pliers, ground using a battery-operated grinder or left intact. The
      effects of the intervention on weaning weight, preweaning mortality, facial
      lesions, gum damage and arthritis in litters of pigs were recorded, as was the
      incidence of udder damage of the sows. Weight gain and facial damage postweaning
      of pigs within each intervention group were recorded. The cost:benefit of each
      intervention was determined. RESULTS: Average weaning weight of pigs whose teeth
      were clipped was higher than of those whose teeth were ground but not of those
      with intact teeth. Clipping resulted in fewer preweaning deaths than both
      unclipped and ground litters due to fewer overlays. The incidence and severity of
      face scarring was higher in unclipped litters than clipped and ground litters.
      Treatment had no effect on face scars at weaning, udder damage, post-treatment
      fostering, time of preweaning deaths or postweaning weight gain. There was an
      additional labour cost of 6 cents per pig with teeth clipping. CONCLUSION: This
      study supports teeth clipping of sucking pigs because there are welfare,
      production and financial benefits including reduced facial damage and preweaning
      mortality.

PMID- 15478732
TI  - Use of copper sulphate for the treatment of dermatophilosis ('brown spot'
      disease) in farmed crocodiles.

PMID- 15478733
TI  - Sick of hospital bills.

PMID- 15478734
TI  - Health-care battle. How they would fix it.

PMID- 15478735
TI  - Kicking the big-car habit.

PMID- 15478736
TI  - Saving the smart kids.

PMID- 15478737
TI  - Teen suicide pills? An FDA panel calls for tough labels on antidepressants. What
      it means for you.

PMID- 15478738
TI  - Treatment of pediatric amblyopia.

PMID- 15478739
TI  - When do you perform an examination under anesthesia?

PMID- 15478740
TI  - Primary congenital glaucoma: 2004 update.
AB  - BACKGROUND: Primary congenital glaucoma is the most frequent childhood glaucoma
      and an important cause of blindness. We describe the current understanding
      regarding this disease, the evaluation of children with it, and its treatment.
      PATIENTS AND METHODS: We accessed information derived from a review of 287
      patients with primary congenital glaucoma and current published data related to
      primary congenital glaucoma. RESULTS: The nomenclature for childhood glaucoma has
      been inconsistent, but is clarified for children with primary congenital
      glaucoma. The epidemiology of primary congenital glaucoma notes its variable
      incidence worldwide. Familial occurrence supports autosomal recessive
      transmission; chromosomal loci have been identified, and the CYP1B1 gene has been
      identified and clinically correlated. The histopathology of eyes with primary
      congenital glaucoma confirms the presence of a variable trabecular meshwork
      anomaly and the absence of an imperforate membrane. Children with primary
      congenital glaucoma are diagnosed after recognition of corneal signs and symptoms
      of glaucoma. CONCLUSIONS: The examinations of patients with primary congenital
      glaucoma must be thorough to distinguish this glaucoma from other types of
      childhood glaucoma, to prepare for surgery, and to follow progress with
      treatment. Medical treatment must be tailored to the pediatric patient.
      Goniosurgery is the definitive procedure of choice for most children with primary
      congenital glaucoma, but other procedures are also used successfully after
      goniosurgery fails or is determined to be inappropriate. Future success will be
      determined by physicians who sustain continued progress for children with
      glaucoma.

PMID- 15478741
TI  - Pars plana lensectomy for the management of ectopia lentis in children.
AB  - BACKGROUND: Nontraumatic ectopia lentis arises from a variety of inherited
      disorders. It may also occur as an isolated abnormality in an otherwise healthy
      individual. Surgical intervention is necessary when lens subluxation causes a
      significant refractive error resulting in amblyopia. PATIENTS AND METHODS: We
      report the results of pars plana lensectomy for nontraumatic ectopia lentis in 24
      eyes of 13 patients and provide data on the merits of this surgical approach.
      better in 17 of 22 eyes and 6/12 or better in 19 of 22 eyes. Other than contact
      lens-related problems, there were no perioperative or postoperative
      complications. CONCLUSIONS: Pars plana lensectomy is a safe, effective procedure
      for the management of ectopia lentis. Visual outcomes are excellent. These
      findings should encourage earlier surgery when indicated to prevent amblyopia and
      improve visual acuity.

PMID- 15478742
TI  - Surgical treatment of advanced chronic angle closure glaucoma in Weill-Marchesani
      syndrome.
AB  - PURPOSE: To describe the surgical treatment of advanced chronic angle closure
      glaucoma in Weill-Marchesani syndrome. PATIENTS AND METHODS: Two children with
      Weill-Marchesani syndrome (4 eyes) undergoing lensectomy, anterior vitrectomy,
      and sutured intraocular lens (IOL) and Molteno tube shunt surgery at Wills Eye
      Hospital were prospectively studied. Visual acuity and intraocular pressure (IOP)
      were recorded. RESULTS: Both patients presented with increasing myopia and
      advanced glaucomatous damage. Laser iridotomy was ineffective in deepening the
      anterior chamber. The first patient developed a flat anterior chamber after
      trabeculectomy. At the 12-month follow-up visit, all 4 eyes had an important
      decrease in IOP and cupping after combined lensectomy, anterior vitrectomy, and
      sutured IOL and Molteno tube shunt placement. One eye had a transitory
      postoperative choroidal effusion and retinal detachment that resolved
      spontaneously. CONCLUSIONS: Advanced chronic angle closure glaucoma in Weill
      Marchesani syndrome may be treated with a combination of lensectomy, anterior
      vitrectomy, and sutured IOL and Molteno tube shunt surgery. In early cases,
      prophylactic peripheral iridotomies should be stressed.

PMID- 15478743
TI  - Symmetrical bilateral lens colobomas in two brothers.
AB  - True lens coloboma is a rare developmental disorder usually caused by missing
      lens zonules in the equatorial area of the lens. Bilateral cases are rare. We
      report bilateral superonasal lens colobomas in two brothers whose parents are
      first cousins.

PMID- 15478744
TI  - Solitary retinal astrocytoma in an infant.
AB  - A 5-month-old infant presented with a solitary retinal astrocytoma that
      clinically and ultrasonographically mimicked retinoblastoma. The diagnosis was
      established on histopathologic examination. There was no systemic evidence of
      tuberous sclerosis or neurofibromatosis. Thus, solitary, large, retinal
      astrocytomas can occur in the absence of any systemic manifestations.

PMID- 15478745
TI  - Natural history of acquired retinal oxalosis in a child.
AB  - We report the natural history of acquired retinal oxalosis in a child with
      chronic renal failure. The clinical manifestations were characterized by a
      transient crystalline retinopathy, but stable, diffuse, flecked retina-like
      changes and focal hypertropic retinal pigment epithelial lesions. The
      pathophysiology and previous reports of retinal oxalosis are reviewed.

PMID- 15478746
TI  - Ocular manifestations and surgical management of lid coloboma in a Chinese infant
      with linear nevus sebaceous syndrome.
AB  - An 8-month-old Chinese girl with linear nevus sebaceous syndrome had a right
      upper lid coloboma and right superior scleral ectasia. At 20 months old,
      successful surgical repair of the lid coloboma was performed with particular
      attention paid to the sclera ectasia.

PMID- 15478747
TI  - Are long compound words identified serially via their constituents? Evidence from
      an eye-movement-contingent display change study.
AB  - The processing of two-constituent 12- to 18-letter Finnish compound nouns was
      studied by using an eye-movement-contingent display change technique. In the
      display change condition, all but the first 2 letters of the second constituent
      were replaced by visually similar letters until the eyes moved across an
      invisible boundary. When the eyes crossed the boundary, the second constituent
      was changed to its intended form. In the control condition, there was no display
      change. The frequency of the first constituent was also varied. The major
      findings were that (1) fixation time on the first constituent was strongly
      affected by the frequency of the first constituent but was not at all affected by
      whether the second constituent was visible, but (2) fixation time on the word
      subsequent to the first constituent's having been left was strongly affected by
      the display change. These results are most parsimoniously explained by the serial
      access of the two constituents for these long compound words.

PMID- 15478748
TI  - Recognizing cognates and interlingual homographs: effects of code similarity in
      language-specific and generalized lexical decision.
AB  - In four experiments, we investigated how cross-linguistic overlap in semantics,
      orthography, and phonology affects bilingual word recognition in different
      variants of the lexical decision task. Dutch-English bilinguals performed a
      language-specific or a generalized lexical decision task including words that are
      spelled and/or pronounced the same in English and in Dutch and that matched one
      language control words from both languages. In Experiments 1 and 3, "false
      friends" with different meanings in the two languages (e.g., spot) were
      presented, whereas in Experiments 2 and 4 cognates with the same meanings across
      languages (e.g., film) were presented. The language-specific Experiments 1 and 2
      replicated and qualified an earlier study (Dijkstra, Grainger, & Van Heuven,
      1999). In the generalized Experiment 3, participants reacted equally quickly on
      Dutch-English homographs and Dutch control words, indicating that their response
      was based primarily on the fastest available orthographic code (i.e., Dutch). In
      Experiment 4, cognates were recognized faster than English and Dutch controls,
      suggesting coactivation of the cognates' semantics. The nonword results indicate
      that the bilingual rejection procedure can, to some extent, be language specific.
      All results are discussed within the BIA+ (bilingual interactive activation)
      model for bilingual word recognition.

PMID- 15478749
TI  - Violating stereotypes: eye movements and comprehension processes when text
      conflicts with world knowledge.
AB  - We investigated the effect of discourse context on the access of word meaning
      during reading. Target words were role names (e.g., electrician) for which there
      was a gender stereotype (e.g., electricians are stereotypically male). Target
      sentences contained a reflexive pronoun that referred to the role name (e.g., The
      electrician taught herself ...). Participants read these target sentences with or
      without paragraph context while their eye movements were monitored. In the
      absence of discourse context and in neutral discourse contexts, fixation times on
      the reflexive pronoun and immediately following the pronoun were inflated when
      the pronoun specified a gender that mismatched the stereotype, indicating that
      the gender stereotype was activated upon encountering the role name. When prior
      discourse context indicated the gender of the role-named character, this mismatch
      effect was eliminated. The mismatch effect indicates that gender stereotypes are
      automatically activated in the absence of disambiguating information. The lack of
      an effect when gender has previously been specified is consistent with the
      lexical reinterpretation model proposed by Hess, Foss, and Carroll (1995).

PMID- 15478750
TI  - Reading units that include interword spaces: filling spaces around a letter can
      facilitate letter detection.
AB  - College students searched for the letter "a" in prose passages typed normally,
      with an asterisk (Experiments 1 and 2) or the letter "x" (Experiment 3) replacing
      every interword space, or with asterisks replacing only some of the interword
      spaces (Experiment 2). Contrary to predictions based on masking through lateral
      interference but consistent with predictions based on studies of eye movement
      monitoring and unitization, asterisks or instances of the letter "x" surrounding
      the word "a" actually made the letter "a" easier to detect in that word, but
      generally not in other words in the text. It is concluded that for very common
      words, reading units may extend beyond the word boundary to include the
      surrounding interword spaces.

PMID- 15478751
TI  - Negations and natural sampling in data selection: ecological versus heuristic
      explanations of matching bias.
AB  - Matching bias occurs when people ignore negations when testing a hypothesis--for
      example, if A, then not 2--and select possible data types that are named in the
      hypothesis (i.e., A and 2; Evans & Lynch, 1973). There are two explanations of
      this bias: the heuristic account and the contrast class account. The latter is
      part of Oaksford and Chater's (1994) ecological approach to data selection. On
      this account, a contrast set (i.e., birds that are not ravens) has a higher
      probability than the original set (i.e., birds that are ravens). This article
      reports two experiments in which these accounts make divergent predictions. The
      same materials were used as those in Yama (2001), who found more support for the
      heuristic approach. Experiment 1 replicated Yama with Western participants.
      Experiment 2 used a procedure introduced by Oaksford and Wakefield (2003). Rather
      than present participants with one of each of the four possible data types all at
      once, 50 were presented one at a time. The proportions of each data type
      reflected the relevant probabilities. The results supported the ecological
      approach, showing that people constructed contrast sets that strongly influenced
      their data selection behavior. The results were not consistent with the heuristic
      approach.

PMID- 15478752
TI  - Disrupting feedback processing interferes with rule-based but not information
      integration category learning.
AB  - The effect of a sequentially presented memory scanning task on rule-based and
      information-integration category learning was investigated. On each trial in the
      short feedback-processing time condition, memory scanning immediately followed
      categorization. On each trial in the long feedback-processing time condition,
      categorization was followed by a 2.5-sec delay and then memory scanning. In the
      control condition, no memory scanning was required. Rule-based category learning
      was significantly worse in the short feedback-processing time condition than in
      the long feedback-processing time condition or control condition, whereas
      information-integration category learning was equivalent across conditions. In
      the rule-based condition, a smaller proportion of observers learned the task in
      the short feedback-processing time condition, and those who learned took longer
      to reach the performance criterion than did those in the long feedback-processing
      time or control condition. No differences were observed in the information
      integration task. These results provide support for a multiple-systems approach
      to category learning and argue against the validity of single-system approaches.

PMID- 15478753
TI  - Information processing and reasoning with premises that are empirically false:
      interference, working memory, and processing speed.
AB  - In this study, we looked at the contributions of individual differences in
      susceptibility to interference and working memory to logical reasoning with
      premises that were empirically false (i.e., not necessarily true). A total of 97
      university students were given a sentence completion task for which a subset of
      stimuli was designed to generate inappropriate semantic activation that
      interfered with the correct response, a measure of working memory capacity, and a
      series of logical reasoning tasks with premises that were not always true. The
      results indicate that susceptibility to interference, as measured by the error
      rate on the relevant subset of the sentence completion task, and working memory
      independently account for variation in reasoning performance. The participants
      who made more errors in the relevant portion of the sentence completion task also
      showed more empirical intrusions in the deductive reasoning task, even when the
      effects of working memory were partialed out. Working memory capacity was more
      clearly related to processes involved in generating uncertainty responses to
      inferences for which there was no certain conclusion. A comparison of the results
      of this study with studies of children's reasoning suggests that adults are
      capable of more selective executive processes than are children. An analysis of
      latency measures on the sentence completion task indicated that high working
      memory participants who made no errors on the sentence completion task used a
      strategy that involved slower processing speed, as compared with participants
      with similar levels of working memory who did make errors. In contrast, low
      working memory participants who made no errors on the sentence completion task
      had relatively shorter reaction times than did comparable participants who did
      make errors.

PMID- 15478754
TI  - Episodic generation can cause semantic forgetting: retrieval-induced forgetting
      of false memories.
AB  - In two experiments, we tested whether false recognition and false recall were
      prone to retrieval-induced forgetting, using the retrieval practice paradigm
      (Anderson, Bjork, & Bjork, 1994). Participants encoded lists of cue-target word
      pairs associated with a nonpresented, critical theme word and then engaged in
      retrieval practice for half of the word pairs from half of the lists. As
      expected, unpracticed targets from practiced lists were recognized (Experiment 1)
      and recalled (Experiment 2) less well than those from unpracticed lists. In
      addition, false recognition and false recall of critical items associated with
      practiced lists was lower than false recognition and false recall of items
      associated with unpracticed lists. We argue that false memories are prone to
      inhibitory mechanisms engendered by the retrieval practice paradigm. The results
      are consistent with the claim that semantically activated critical themes
      interfere with the episodic retrieval of list words and that inhibition decreases
      the activation level of these interfering memory representations during retrieval
      practice.

PMID- 15478755
TI  - Part-list cuing as instructed retrieval inhibition.
AB  - The reexposure of a subset of learned material as a retrieval cue can impair
      recall of the remaining material. Like part-list relearning--the reexposure of
      learned material for additional learning--this part-list cuing is often assumed
      to be the result of output order biases at test, caused by the increased strength
      of the reexposed material. We directly compared the effects of cuing and
      relearning when controlling for output order biases. In addition, we compared the
      two forms of reexposure with the effect of part-list retrieval. Both part-list
      cuing and part-list retrieval reduced recall performance for the remaining
      material. By contrast, part-list relearning had no such detrimental effect. These
      results indicate that the effect of reexposure depends on whether material is
      reexposed as a cue or for relearning, suggesting that part-list cuing reflects an
      instructional effect. Evidence is provided that part-list cuing leads to
      instructed covert retrieval of cue items and causes retrieval inhibition of
      noncue items, similar to how overt retrieval inhibits nonretrieved items.

PMID- 15478756
TI  - Perceptual and conceptual training mediate the verbal overshadowing effect in an
      unfamiliar domain.
AB  - Describing memory for a nonverbal perceptual stimulus can impair recognition.
      This verbal overshadowing effect may occur when perceptual expertise exceeds
      verbal expertise, but previous evidence for this hypothesis has been strictly
      correlational. We conducted two experiments, exploring the relation between
      expertise and verbal overshadowing by manipulating perceptual and conceptual
      knowledge. Participants received perceptual training (categorizing mushrooms),
      conceptual training (lecture), or no training, then viewed a mushroom and
      described it or not. A recognition test followed. In Experiment 1, perceptual
      training increased susceptibility to verbalization relative to the no training
      condition. However, conceptual training did not insulate individuals from the
      verbal overshadowing effect. Experiment 2 was modified to enhance both forms of
      training. It replicated the finding that perceptual training increases
      vulnerability to verbal overshadowing, and indicated that, when sufficiently
      emphasized, verbalization may be useful following conceptual training. The
      results demonstrate the role that different forms of learning and expertise may
      play in mediating language influences on recognition memory.

PMID- 15478757
TI  - Relating distinctive orthographic and phonological processes to episodic memory
      performance.
AB  - Three experiments examined the role of three distinctive perceptual factors in
      recognition and recall memory. Using a subject-paced presentation rate, the first
      two experiments (recognition and recall) examined (1) the number of phonological
      to-orthographic neighbors, (2) phonological-to-orthographic consistency, and (3)
      orthographic-to-phonological consistency. The third experiment (recall)
      reexamined the number of phonological-to-orthographic neighbors, using an
      experimenter-paced presentation rate of 2 sec per item. In both recognition and
      recall memory tasks, the number of phonological-to-orthographic neighbors
      influenced memory performance, whereas the two types of consistency did not. The
      results indicate that having fewer phonological-to-orthographic neighbors (i.e.,
      having distinct mappings between orthography and phonology, and between phonology
      and orthography, e.g., pulp) relieve words from interference in episodic memory
      tests for such words. Furthermore, words that are indistinct in terms of these
      mappings (e.g., tuck) are subject to interference from words with similar
      representations (e.g., luck, buck, stuck), and this weakens the memory trace for
      a particular word.

PMID- 15478758
TI  - Repetition priming from moving faces.
AB  - Recent experiments have suggested that seeing a familiar face move provides
      additional dynamic information to the viewer, useful in the recognition of
      identity. In four experiments, repetition priming was used to investigate whether
      dynamic information is intrinsic to the underlying face representations. The
      results suggest that a moving image primes more effectively than a static image,
      even when the same static image is shown in the prime and the test phases
      (Experiment 1). Furthermore, when moving images are presented in the test phase
      (Experiment 2), there is an advantage for moving prime images. The most priming
      advantage is found with naturally moving faces, rather than with those shown in
      slow motion (Experiment 3). Finally, showing the same moving sequence at prime
      and test produced more priming than that found when different moving sequences
      were shown (Experiment 4). The results suggest that dynamic information is
      intrinsic to the face representations and that there is an advantage to viewing
      the same moving sequence at prime and test.

PMID- 15478759
TI  - Working memory and phonological processing as predictors of children's
      mathematical problem solving at different ages.
AB  - The study explored the contribution of working memory (WM) to mathematical
      problem solving in younger (8-year-old) and older (11-year-old) children. The
      results showed that (1) significant age-related differences in WM performance
      were maintained when measures of phonological processing (i.e., digit naming
      speed, short-term memory, phonological deletion) were partialed from the
      analysis; (2) WM predicted solution accuracy of word problems independently of
      measures of problem representation, knowledge of operations and algorithms,
      phonological processing, fluid intelligence, reading, and math skill; and (3) a
      second-order WM factor was correlated with problem solving, suggesting that a
      general or executive system underlies age-related performance. The results were
      interpreted as support for the notion that the executive system was an important
      predictor of age-related changes in problem solving beyond the contribution of
      math and reading skills, and this system operates independently of the
      phonological system and domain-specific knowledge in predicting solution
      accuracy.

PMID- 15478760
TI  - Spatial structure of quantitative representation of numbers: evidence from the
      SNARC effect.
AB  - Dehaene, Bossini, and Giraux (1993) revealed that subjects responded to large
      numbers faster with the choice on the right than with the choice on the left,
      whereas the reverse held true for small numbers (SNARC effect). According to
      Dehaene et al. (1993), the SNARC effect depends on the quantitative
      representation of number, such as a left-to-right-oriented analog number line.
      The main goal of the present study was twofold: first, to investigate whether the
      vertical SNARC effect could be observed, and, second, to verify whether Dehaene
      et al.'s (1993) explanation of the SNARC effect is correct. Experiments 2A and 2B
      showed the vertical SNARC effect in a parity judgment task. Subjects responded to
      large numbers faster with the top choice than with the bottom choice, whereas the
      reverse held true for small numbers. However, Experiment 3 failed to show the
      SNARC effect in a number magnitude judgment task, suggesting that the
      quantitative representation could be dissociated from the spatial code that
      produces the SNARC effect.

PMID- 15478761
TI  - A new look at recognition in the Brown-Peterson distractor paradigm: toward the
      application of new methodology to unsolved problems of recognition memory.
AB  - Data from a recognition version of the classic Brown-Peterson short-term memory
      paradigm was analyzed using a modified version of the conjoint recognition model
      (Brainerd, Reyna, & Mojardin, 1999), which assumes that recognition is based on
      either a verbatim comparison of the recognition probe and the target item or a
      gist comparison of the items. Separate groups of participants were instructed to
      judge whether the recognition probe was an item from the current trial (exclusion
      condition), a previous trial (prior-only condition), or either the current or the
      previous trial (inclusion condition). The concept of gist is commonly thought of
      as meaning based. Our interpretation of the results suggests that the concept of
      gist need also emphasize similarity of environmental context. In addition, the
      results show that priming the recognition probe affects a participant's decision
      bias but does not enhance or impair the memory traces on which the recognition
      judgments are based. An additional analysis using Batchelder and Riefer's (1990)
      source-monitoring model supports the observation that priming affects only
      decision bias.

PMID- 15478762
TI  - Efficacy of a long-acting formulation of ceftiofur crystalline-free acid for the
      treatment of naturally occurring infectious bovine keratoconjunctivitis.
AB  - OBJECTIVE: To evaluate the efficacy of ceftiofur crystalline-free acid (CCFA)
      administered into the posterior aspect of an ear for treatment of corneal
      ulceration associated with naturally occurring infectious bovine
      keratoconjunctivitis (IBK). ANIMALS: 78 beef calves located at Sierra Foothills
      Field Station (SFS) and 52 calves located at a commercial dairy (CD). All calves
      were from 3 to 9 months old. PROCEDURE: At each site, calves were randomly
      allocated to 1 of 2 treatment groups by use of a block design determined by
      corneal ulcer size. A single dose of CCFA (6.6 mg of ceftiofur equivalents/kg,
      s.c.) was administered into the posterior aspect of a pinna. A second group of
      calves received a single dose of vehicle (0.03 mL/kg, s.c.; controls). Corneal
      ulcers were photographed, and clinical signs were assessed in calves every 3 to 4
      days for 21 days. RESULTS: A positive treatment effect was detected at SFS.
      Results at the CD were inconclusive because ulcer healing occurred rapidly in
      control and CCFA-treated calves. At SFS, treatment with CCFA resulted in shorter
      mean healing times, smaller corneal ulcer surface area measurements, amelioration
      of ocular discharge and photophobia, and a 50% increase in the percentage of
      calves healed by day 14. After adjustment for initial corneal ulcer size,
      treatment with CCFA resulted in a 4-fold increase in the odds of corneal ulcer
      healing by day 14, compared with controls. CONCLUSIONS AND CLINICAL RELEVANCE: A
      single dose of CCFA administered into the posterior aspect of a pinna had a
      positive treatment effect against naturally occurring IBK in calves with corneal
      ulcerations.

PMID- 15478763
TI  - Comparison of lactated Ringer's solution and a physiologically balanced 6%
      hetastarch plasma expander for the treatment of hypotension induced via blood
      withdrawal in isoflurane-anesthetized dogs.
AB  - OBJECTIVE: To compare the effects of lactated Ringer's solution (LRS) with those
      of a physiologically balanced 6% hetastarch plasma expander administered to
      isoflurane-anesthetized dogs with hypotension induced by blood withdrawal.
      ANIMALS: 12 healthy Beagles. PROCEDURE: Blood was withdrawn from isoflurane
      anesthetized dogs (volume withdrawn measured) to a systolic arterial blood
      pressure (SAP) of 80 mm Hg. Six dogs each received either LRS or hetastarch
      solution (90 mL/kg/h, i.v.). Hemodynamic variables, pH, blood gas concentrations,
      PCV, serum electrolyte and total protein concentrations, and colloid osmotic
      pressure (COP) were determined at baseline, while SAP was 80 mm Hg, and after
      fluid treatment. The volume of fluid administered and rate of return of SAP to
      within 10% of baseline values were recorded. RESULTS: Mean +/- SD volume of blood
      withdrawn to decrease SAP to 80 mm Hg was 173 +/- 38 mL. Hemodynamic variables
      decreased after blood withdrawal but returned to baseline values more rapidly
      after infusion of a smaller volume of hetastarch solution, compared with the
      response to LRS infusion. Whereas PCV and serum total protein concentration
      decreased after administration of either solution, COP decreased only after
      administration of LRS. The total volume of hetastarch solution and LRS required
      to restore and maintain SAP to within 10% of baseline values was 1.1 +/- 0.9 and
      4.4 +/- 1.7 times greater than the volume of blood removed, respectively.
      CONCLUSIONS AND CLINICAL RELEVANCE: Compared with LRS infusion, smaller volumes
      of hetastarch solution normalized and maintained SAP without lowering COP in
      isoflurane-anesthetized dogs after blood withdrawal.

PMID- 15478764
TI  - Purification and partial characterization of feline pepsinogen.
AB  - OBJECTIVE: To purify and partially characterize feline pepsinogen (fPG) from the
      gastric mucosa and compare fPG with PGs of other species. SAMPLE POPULATION:
      Stomachs of 6 cats. PROCEDURE: A crude protein extract was prepared from the
      gastric mucosa of feline stomachs. Feline PG A was purified by ammonium sulfate
      precipitation, weak-anion-exchange chromatography, size-exclusion chromatography,
      and strong-anion exchange chromatography. Partial characterization consisted of
      estimation of molecular weights (MWs) and isoelectric points, N-terminal amino
      acid sequencing, and investigation of susceptibility to pepstatin inhibition.
      RESULTS: Several fPG A-group isoforms were identified. The MWs of the isoforms
      ranged from 37,000 to 44,820. Isoelectric points were all < pH 3.0. The
      proteolytic activity of the activated PGs was inhibited completely by pepstatin
      in a range of equimolar to 10-fold molar excess. The specific absorbance of fPG A
      was 1.29. The N-terminal amino acid sequence of the first 25 residues of the
      predominant fPG A7 had 75%, 72%, 64%, and 56% homology with PG A of dogs,
      rabbits, cattle, and humans, respectively. Sequences of 4 other fPG A-group
      isoforms were similar to fPG A7. All isoforms were immunologically cross-reactive
      with sheep anti-fPG A7 antiserum. CONCLUSIONS AND CLINICAL RELEVANCE: PG A is the
      only identified type of PG in cats and, similar to pg in other species, comprises
      multiple isoforms. The availability of fPG A may be used to facilitate the
      development of an immunoassay to quantify serum fPG A as a potential marker for
      gastric disorders in cats.

PMID- 15478765
TI  - Comparison of results for serologic testing and a polymerase chain reaction assay
      to determine the prevalence of stray dogs in eastern Tennessee seropositive to
      Ehrlichia canis.
AB  - OBJECTIVE: To determine the prevalence of stray dogs in eastern Tennessee
      seropositive to Ehrlichia canis and examine the correlation between results for
      an ELISA, indirect immunofluorescent antibody (IFA) test, and polymerase chain
      reaction (PCR) assay. SAMPLE POPULATION: Blood samples obtained from 90 adult
      dogs admitted to an animal shelter in eastern Tennessee. PROCEDURE: Serum samples
      were analyzed for antibodies against E. canis by use of a commercially available
      ELISA kit, 2 IFA tests, and a PCR assay; testing was performed at the University
      of Tennessee (TN) and North Carolina State University (NCSU). The PCR
      amplification was performed by use of DNA extracted from EDTA-anticoagulated
      blood and primers designed to amplify DNA of Ehrlichia spp. RESULTS: Antibodies
      against E. canis were detected in only 1 dog by use of the ELISA. By IFA testing
      at TN, 10 of 90 (11%) dogs were seroreactive against E. canis antigens, all of
      which had medium to high titers to E. canis. Only 5 of the 10 TN seroreactors
      were also reactive against E. canis antigens in IFA tests conducted at NCSU, and
      all 5 had low to medium titers. The DNA of Ehrlichia spp was not amplified in any
      blood samples by use of PCR assays conducted at the TN or NCSU. CONCLUSIONS AND
      CLINICAL RELEVANCE: The discordant ELISA, IFA, and PCR results obtained in this
      study were unexpected and may have been related to exposure of dogs to an
      Ehrlichia species other than E. canis, such as E. ewingii.

PMID- 15478766
TI  - Effects of a menthol-based analgesic balm on pressor responses evoked from muscle
      afferents in cats.
AB  - OBJECTIVE: To evaluate changes in heart rate (HR) and mean arterial pressure
      (MAP) as indicators of changes in pressor response for muscle afferents after
      topical application of menthol (MEN)-based analgesic balm. ANIMALS: 11
      decerebrate cats. PROCEDURE: Pressor responses were reflexively evoked by static
      contraction of hind limb muscles, which are caused by group III and IV afferents.
      Responses were monitored without interference from anesthesia or effects of
      higher brain function by the use of decerebrate cats. After obtaining baseline
      data, MEN analgesic balm (1.9%) was applied to the skin over contracting muscles
      of 1 hind limb in 6 cats; petrolatum was applied to 5 control cats. Muscle
      contractions were evoked every 10 minutes, alternating between hind limbs, for
      120 minutes. Peak MAP and HR were analyzed. RESULTS: Peak MAP responses evoked by
      static muscle contraction for the ipsilateral hind limb were significantly
      attenuated 20 minutes after application, but approached baseline values 40
      minutes after application. The pressor response was significantly decreased 20
      minutes after application during the last 12 seconds of the stimulus, which was
      attributed to group IV afferents. There were no significant differences in HR
      responses. CONCLUSIONS AND CLINICAL RELEVANCE: Application of MEN analgesic balm
      to the skin over contracting muscles significantly decreased the pressor response
      to static muscle contractions. This suggests that topical application of MEN has
      effects on responses evoked from receptors located in muscles. The MEN analgesic
      balm appeared to attenuate the pressor response 20 minutes after application, but
      it was a short-term effect.

PMID- 15478767
TI  - Influence of weight bearing and hoof position on Doppler evaluation of lateral
      palmar digital arteries in healthy horses.
AB  - OBJECTIVE: To describe the pulsed-wave Doppler tracing of the equine lateral
      palmar digital artery and its modification in relation to standardized changes in
      posture. ANIMALS: 17 healthy Saddlebred horses. PROCEDURES: Pulsed-wave Doppler
      examinations of left and right lateral palmar digital arteries of the horses were
      performed. The baseline examination was performed on each forelimb while horses
      were standing squarely with the body weight equally distributed among the 4 limbs
      (BED position). For each forelimb, the examination was repeated during 3
      standardized modifications of the horse's posture (non-weight-bearing [NWB]
      position, full weight-bearing [FWB] position, and a position involving
      hyperextension of the distal interphalangeal joint [HE position]). In each
      position, mean values of systolic peak velocity, first and second diastolic peak
      velocity, end-diastolic velocity, mean velocity, and resistive index were
      calculated. Data obtained in each different posture were compared statistically.
      RESULTS: No significant differences in blood flow variables were detected between
      the left and right forelimbs. However, significant differences were detected in
      values of first diastolic velocity, second diastolic velocity, mean velocity, and
      resistive index between the NWB position and FWB position. Also, end-diastolic
      velocity in the NWB position was significantly different from that recorded in
      the HE position. CONCLUSIONS AND CLINICAL RELEVANCE: The pulsed-wave Doppler
      tracing of the equine lateral palmar digital artery was modified considerably
      with changes in posture. This suggests that the use of a precisely standardized
      posture for horses is required to obtain repeatable data.

PMID- 15478769
TI  - Response of induced bone defects in horses to collagen matrix containing the
      human parathyroid hormone gene.
AB  - OBJECTIVE: To determine whether human parathyroid hormone (hPTH) gene in collagen
      matrix could safely promote bone formation in diaphyseal or subchondral bones of
      horses. ANIMALS: 8 clinically normal adult horses. PROCEDURE: Amount, rate, and
      quality of bone healing for 13 weeks were determined by use of radiography,
      quantitative computed tomography, and histomorphometric analysis. Diaphyseal
      cortex and subchondral bone defects of metacarpi were filled with hPTH(1-34) gene
      activated matrix (GAM) or remained untreated. Joints were assessed on the basis
      of circumference, synovial fluid analysis, pain on flexion, lameness, and gross
      and histologic examination. RESULTS: Bone volume index was greater for cortical
      defects treated with hPTH(1-34) GAM, compared with untreated defects. Bone
      production in cortical defects treated with hPTH(1-34) GAM positively correlated
      with native bone formation in untreated defects. In contrast, less bone was
      detected in hPTH(1-34) GAM-treated subchondral bone defects, compared with
      untreated defects, and histology confirmed poorer healing and residual collagen
      sponge. CONCLUSIONS AND CLINICAL RELEVANCE: Use of hPTH(1-34) GAM induced greater
      total bone, specifically periosteal bone, after 13 weeks of healing in cortical
      defects of horses. The hPTH(1-34) GAM impeded healing of subchondral bone but was
      biocompatible with joint tissues. Promotion of periosteal bone formation may be
      beneficial for healing of cortical fractures in horses, but the delay in onset of
      bone formation may negate benefits. The hPTH(1-34) GAM used in this study should
      not be placed in articular subchondral bone defects, but contact with articular
      surfaces is unlikely to cause short-term adverse effects.

PMID- 15478768
TI  - Role of the tendons of the biceps brachii and infraspinatus muscles and the
      medial glenohumeral ligament in the maintenance of passive shoulder joint
      stability in dogs.
AB  - OBJECTIVE: To objectively evaluate the effect of transecting the tendon of the
      biceps brachii muscle (BBT), tendon of the infraspinatus muscle (IFS), or medial
      glenohumeral ligament (MGHL) on shoulder joint stability in canine cadavers.
      SAMPLE POPULATION: 81 forelimbs from mature dogs. PROCEDURE: Cadaver forelimbs
      were placed in a testing frame and axially preloaded with 4 kg of weight.
      Shoulder joint stability was tested in neutral joint position, flexion, and
      extension before and after transection of the BBT (n = 37), IFS (37), or MGHL
      (7). Humeral translation relative to the glenoid was induced by applying a 3-kg
      load in each of 3 directions (cranial, lateral, and medial) and quantitatively
      measured by use of an electromagnetic motion tracking system. Peak translational
      data were compared in each joint position before and after transection of the
      BBT, IFS, or MGHL. RESULTS: When tested in neutral position, the cranial,
      lateral, and medial translation of the humerus was significantly increased after
      BBT transection. In the flexed position, translation of the humerus in the
      cranial and lateral directions was significantly increased after BBT transection.
      In the extended position, the medial translation of the humerus was significantly
      increased after BBT transection. Complete medial luxation of all humeral heads
      occurred following transection of the MGHL. CONCLUSIONS AND CLINICAL RELEVANCE:
      The BBT contributes to passive shoulder joint stability in dogs, particularly in
      the neutral and flexed positions. It also provides medial stability during
      shoulder joint extension. Complete luxation of the joint occurs when the MGHL is
      transected.

PMID- 15478770
TI  - Effect of strain and serotype of vesicular stomatitis virus on viral shedding,
      vesicular lesion development, and contact transmission in pigs.
AB  - OBJECTIVE: To determine whether pigs can be infected with strains of vesicular
      stomatitis virus New Jersey (VSV-NJ) and vesicular stomatitis virus Indiana (VSV
      I) isolated during recent vesicular stomatitis outbreaks that primarily involved
      horses in the western United States and determine the potential for these viruses
      to be transmitted by contact. ANIMALS: 128 pigs. PROCEDURE: Pigs were challenged
      with VSV-NJ or VSV-I from the 1995 and 1997 outbreaks of vesicular stomatitis in
      the western United States, respectively, or with VSV-NJ (OS) associated with
      vesicular stomatitis in feral pigs on Ossabaw Island, Ga. Pigs (3/group) were
      inoculated with each virus via 3 routes and evaluated for viral shedding,
      seroconversion, and the development of vesicular lesions. In another experiment,
      the potential for contact transmission of each virus from experimentally infected
      to naive pigs was evaluated. RESULTS: Infection of pigs was achieved for all 3
      viruses as determined by virus isolation and detection of seroconversion. In
      inoculated pigs, all 3 viruses were isolated from multiple swab samples at
      concentrations sufficient to infect other pigs. However, compared with results
      obtained with the 2 VSV-NJ strains, viral titers associated with VSV-I were low
      and the duration of virus shedding was reduced. Results from the contact
      transmission trials were consistent with these results; virus transmission was
      detected most frequently with the VSV-NJ strains. CONCLUSIONS AND CLINICAL
      RELEVANCE: Pigs can be infected with VSV-NJ and VSV-I. Differences in the extent
      of viral shedding and potential for contact transmission were apparent between
      serotypes but not between the VSV-NJ strains investigated.

PMID- 15478771
TI  - Correlation of computed tomographic images with anatomic features of the abdomen
      of ringed seals (Phoca hispida).
AB  - OBJECTIVE: To correlate anatomic features of the abdomen of the ringed seal
      (Phoca hispida) identified in plastinated cross-sections with images obtained via
      computed tomography (CT) and thereby establish reference standards for normal
      abdominal organ size and position in this species. SAMPLE POPULATION: 2 adult
      male ringed seal cadavers. PROCEDURE: With the seal in sternal recumbency, CT
      images of the abdomen were acquired by use of a 4th-generation CT scanner. Image
      slice thickness was 1 cm, with no interslice gap. After imaging, the abdominal
      region was sectioned transversely into 4-cm slices, which were plastinated and
      photographed. Plastinated slices were matched to their corresponding CT images in
      preparation for anatomic descriptions. RESULTS: Relevant anatomic features were
      identified and labeled on both the plastinated tissue slice and corresponding CT
      image. Normal abdominal organ size and position were assessed, and topographic
      relationships among organs were ascertained. CONCLUSIONS AND CLINICAL RELEVANCE:
      The data obtained provide some reference standards for normal abdominal organ
      size and position in ringed seals. This information may aid researchers of future
      physiologic and clinical studies in this species.

PMID- 15478772
TI  - Effect of trilostane on serum concentrations of aldosterone, cortisol, and
      potassium in dogs with pituitary-dependent hyperadrenocorticism.
AB  - OBJECTIVE: To evaluate the effect of trilostane on serum concentrations of
      aldosterone, cortisol, and potassium in dogs with pituitary-dependent
      hyperadrenocorticism (PDH), compare the degree of reduction of aldosterone with
      that of cortisol, and compare aldosterone concentrations of healthy dogs with
      those of dogs with PDH. ANIMALS: 17 dogs with PDH and 12 healthy dogs. PROCEDURE:
      For dogs with PDH, the initial dose of trilostane was selected in accordance with
      body weight. A CBC count, serum biochemical analyses, and ACTH stimulation tests
      were performed in each dog. Dogs were evaluated 1, 3 to 4, 6 to 8, and 10 to 12
      weeks after initiation of treatment. Healthy dogs were evaluated only once.
      RESULTS: Serum aldosterone concentrations before ACTH stimulation did not change
      significantly after initiation of treatment with trilostane. At each evaluation
      after initiation of treatment, serum aldosterone concentrations after ACTH
      stimulation were significantly lower than corresponding concentrations before
      initiation of treatment. The overall effect of trilostane on serum aldosterone
      concentration was less pronounced than the effect on serum cortisol
      concentration. Median potassium concentrations increased slightly after
      initiation of treatment with trilostane. Dogs with PDH had significantly higher
      serum aldo sterone concentrations before and after ACTH stimulation than healthy
      dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with trilostane resulted in a
      reduction in serum cortisol and aldosterone concentrations in dogs with PDH,
      although the decrease for serum aldosterone concentration was smaller than that
      for serum cortisol concentration. There was no correlation between serum
      concentrations of aldosterone and potassium during treatment.

PMID- 15478773
TI  - Evaluation of experimental methods to induce congenital hypothyroidism in guinea
      pigs for use in the study of congenital hypothyroidism in horses.
AB  - OBJECTIVE: To develop a method to reliably induce congenital hypothyroidism in
      guinea pigs (Cavia porcellus) and assess similarities between the resultant
      developmental abnormalities and those described in horses with congenital
      hypothyroidism. ANIMALS: 35 female guinea pigs and their offspring. PROCEDURE:
      Guinea pigs were allocated to control groups or groups treated with a low-iodine
      diet before and throughout gestation; an s.c. injection of 100 or 200 microCi of
      radioactive iodine 131 (131I) on day 40 of gestation; or 0.1% propylthiouracil
      (PTU) continuously in the drinking water, beginning day 3 or 40 of gestation. In
      all groups, assessments included gestation duration, litter size, proportion of
      stillborn pups, and laboratory analyses in live pups and dams; postmortem
      examinations were performed on all pups and dams and selected tissues were
      examined histologically. RESULTS: Compared with control animals, pups from dams
      receiving a low-iodine diet or 131I s.c. had mild changes in their thyroid glands
      but no grossly or radiographically detectable lesions of hypothyroidism. Pups
      from dams receiving PTU were often stillborn (24/27 pups) and had enlarged
      thyroid glands (characterized by large, variably sized follicles of tall columnar
      epithelium and little or no colloid), an incomplete coat, and radiographically
      detectable skeletal dysgenesis. CONCLUSIONS AND CLINICAL RELEVANCE: Many of the
      lesions detected in guinea pig pups from the experimentally treated dams were
      similar to those described in foals with congenital hypothyroidism. Experimental
      induction of congenital hypothyroidism in guinea pigs may be useful for the study
      of naturally occurring congenital hypothyroidism in horses.

PMID- 15478774
TI  - Evaluation of head-out constant volume body plethysmography for measurement of
      specific airway resistance in conscious, sedated sheep.
AB  - OBJECTIVE: To evaluate the use of a modified whole body plethysmograph in awake
      sheep. ANIMALS: 10 healthy adult sheep. PROCEDURE: Concurrent measurements of
      specific airway resistance (sR(aw)) and pulmonary resistance (R(L)) were obtained
      using a novel noninvasive head-out constant-volume plethysmograph and esophageal
      balloon-pneumotachography, respectively. All data were collected before and after
      external resistive loading with 1 and 5.6 cm H2O/L/s. Functional residual
      capacity (FRC) was measured by helium dilution for computation of airway
      resistance (R(aw)) preloading (R(aw) = sR(aw)/FRC). RESULTS: The sR(aw) and R(L)
      were closely correlated in 10 adult sheep. Additionally, sR(aw), and R(L)
      accurately reflected the magnitude of added resistance. The mean FRC was 52 mL/kg
      and used to calculate R(aw). At baseline, the values for R(aw) were significantly
      correlated with sR(aw) and R(L). CONCLUSIONS AND CLINICAL RELEVANCE: Precise
      measurements of sR(aw) and R(aw) at baseline and sR(aw) after external resistive
      loading were obtained by use of this novel noninvasive plethysmographic
      technology. This method should have application to veterinary patients or animals
      used in research in which noninvasive rapid or serial measurements of sR(aw) in
      the conscious state are required.

PMID- 15478775
TI  - Methicillin resistance of staphylococci isolated from the skin of dogs with
      pyoderma.
AB  - OBJECTIVE: To determine the methicillin-resistant profile of staphylococcal
      isolates from the skin of dogs with pyoderma. ANIMALS: 90 dogs with pyoderma.
      PROCEDURE: Staphylococci isolated from dogs with pyoderma were tested for
      susceptibility to methicillin by use of a standard disk diffusion test with
      oxacillin disks. The DNA extracted from the isolates was tested for the mecA gene
      that encodes the penicillin-binding protein 2a (PBP2a) by use of a polymerase
      chain reaction (PCR) assay. The expression of PBP2a was determined with a
      commercial latex agglutination assay. Species of staphylococcal isolates were
      identified by use of morphologic, biochemical, and enzymatic tests. RESULTS: Most
      of the isolated staphylococci were methicillin-susceptible, coagulase-positive
      Staphylococcus intermedius isolates. Whereas only 2 of 57 S. intermedius isolates
      were resistant to methicillin, approximately half of the isolates had the mecA
      gene and produced PBP2a. Staphylococcus schleiferi was the second most common
      isolate. Widespread resistance to methicillin was found among S. schleiferi
      isolates. More coagulase-negative S. schleiferi isolates were identified with
      mecA gene-mediated resistance to methicillin, compared with coagulase-positive S.
      schleiferi isolates. CONCLUSIONS AND CLINICAL RELEVANCE: The latex agglutination
      assay for the detection of PBP2a expression coupled with the PCR assay for the
      mecA gene may provide new information about emerging antimicrobial resistance
      among staphylococcal isolates.

PMID- 15478776
TI  - Correlation of prostaglandin E2 concentrations in synovial fluid with ground
      reaction forces and clinical variables for pain or inflammation in dogs with
      osteoarthritis induced by transection of the cranial cruciate ligament.
AB  - OBJECTIVE: To evaluate the temporal pattern of prostaglandin (PG) E2
      concentrations in synovial fluid after transection of the cranial cruciate
      ligament (CCL) in dogs and to correlate PGE2 concentrations with ground reaction
      forces and subjective clinical variables for lameness or pain. ANIMALS: 19
      purpose-bred adult male Walker Hounds. PROCEDURE: Force plate measurements,
      subjective clinical analysis of pain or lameness, and samples of synovial fluid
      were obtained before (baseline) and at various time points after arthroscopic
      transection of the right CCL. Concentrations of PGE2 were measured in synovial
      fluid samples, and the PGE2 concentrations were correlated with ground reaction
      forces and clinical variables. RESULTS: The PGE2 concentration increased
      significantly above the baseline value throughout the entire study, peaking 14
      days after transection. Peak vertical force and vertical impulse significantly
      decreased by day 14 after transection, followed by an increase over time without
      returning to baseline values. All clinical variables (eg, lameness, degree of
      weight bearing, joint extension, cumulative pain score, effusion score, and total
      protein content of synovial fluid, except for WBC count in synovial fluid)
      increased significantly above baseline values. Significant negative correlations
      were detected between PGE2 concentrations and peak vertical force (r, -0.5720)
      and vertical impulse (r, -0.4618), and significant positive correlations were
      detected between PGE2 concentrations and the subjective lameness score (r,
      0.5016) and effusion score (r, 0.6817). CONCLUSIONS AND CLINICAL RELEVANCE:
      Assessment of the acute inflammatory process by measurement of PGE2
      concentrations in synovial fluid may be correlated with the amount of pain or
      lameness in dogs.

PMID- 15478777
TI  - Use of pressure platform gait analysis in cats with and without bilateral
      onychectomy.
AB  - OBJECTIVE: To determine peak vertical force (PVF) and vertical impulse (VI) in
      cats that had or had not undergone bilateral forelimb onychectomy. ANIMALS: 26
      healthy adult cats. PROCEDURE: Onychectomized cats (n = 13) had undergone surgery
      more than 6 months prior to the study. The PVF and VI were collected from all
      limbs of each cat with a 2-m pressure platform walkway. Cats were allowed to walk
      at a comfortable velocity, and acceleration was restricted to +/- 0.5 m/s2. Five
      valid trials were recorded for each cat with all trials collected in a single 1
      hour session. All forces were normalized to and expressed as a percentage of the
      cat's body weight. RESULTS: Gait data were successfully collected in all cats. No
      significant difference was found for PVF or VI between cats that had or had not
      had onychectomy. Limb loads were greater in forelimbs than hind limbs for all
      trials. Mean PVF and VI in the forelimbs of cats in the nononychectomy group were
      56.41% and 18.85%, respectively. Mean PVF and VI in the hind limbs of cats in the
      nononychectomy group were 50.22% and 14.56%, respectively. CONCLUSIONS AND
      CLINICAL RELEVANCE: Gait analysis was successfully performed in cats with a
      pressure platform walkway. The absence of differences in PVF and VI between the 2
      groups of cats suggests that bilateral forelimb onychectomy did not result in
      altered vertical forces measured more than 6 months after surgery in cats.

PMID- 15478778
TI  - Evaluation of assays for perinuclear antineutrophilic cytoplasmic antibodies and
      antibodies to Saccharomyces cerevisiae in dogs with inflammatory bowel disease.
AB  - OBJECTIVE: To evaluate the use of immunofluorescence asssays for perinuclear
      antineutrophilic cytoplasmic antibodies (pANCAs) and antibodies to Saccharomyces
      cerevisiae (ASCAs) in dogs with inflammatory bowel disease (IBD) and assess the
      clinical value of these serologic markers of the disease. ANIMALS: 39 dogs with
      IBD, 18 dogs with acute diarrhea, 19 dogs with chronic non-IBD-associated
      diarrhea, 26 healthy dogs of various breeds and age, and 22 healthy young working
      dogs. PROCEDURE: Sera obtained from the dogs in each group were added to canine
      granulocyte- and Saccharomyces cerevisiae-mounted slides for detection of pANCAs
      and ASCAs via immunofluorescence techniques. Sensitivity and specificity (with
      95% confidence intervals [CIs]) were calculated for the group of dogs with IBD
      versus each of the 2 groups of healthy dogs, the group of dogs with acute
      diarrhea, and the group of dogs with chronic non-IBD-associated diarrhea.
      RESULTS: Among the 39 dogs with IBD, 20 yielded positive results via the pANCA
      assay (sensitivity, 0.51 [95% CI, 0.35 to 0.67]) and 17 yielded positive results
      via the ASCA assay (sensitivity, 0.44 [95% CI, 0.22 to 0.69]). The specificity of
      the pANCA assay in the 4 groups of non-IBD-affected dogs ranged from 0.83 (95%
      CI, 0.85 to 0.96) to 0.95 (95% CI, 0.72 to 1.00). CONCLUSIONS AND CLINICAL
      RELEVANCE: Immunofluorescence assays for pANCA and ASCA appear to be useful for
      the detection of IBD in dogs. The pANCA immunofluorescence assay had high
      specificity for canine IBD, and pANCAs appear to be accurate markers of
      intestinal inflammation.

PMID- 15478779
TI  - Spatial dispersal of porcine reproductive and respiratory syndrome virus
      contaminated flies after contact with experimentally infected pigs.
AB  - OBJECTIVE: To determine whether flies can acquire porcine reproductive and
      respiratory syndrome virus (PRRSV) and disperse the virus throughout a designated
      area. ANIMALS: 60 four-month-old pigs. PROCEDURE: On day 0, 28 of 60 pigs were
      inoculated with PRRSV MN 30-100 (index variant). On the same day, 100,000 pupae
      of ochre-eyed houseflies and 100,000 pupae of red-eyed (wild-type) houseflies
      were placed in the swine facility for a release-recapture study. Flies were
      recaptured at 2 locations within the swine facility, 6 locations immediately
      outside the facility, and 30 locations 0.4, 0.8, 1.3, 1.7, 1.9, and 2.3 km from
      the facility. Traps were emptied on days 2, 7, 8, 10, and 14. Samples derived
      from flies were tested by use of a polymerase chain reaction assay, virus DNA was
      sequenced, and viruses were tested for infectivity by means of a swine bioassay.
      RESULTS: PRRSV RNA homologous to the index PRRSV was detected in trapped flies
      collected inside and immediately outside the facility and from 9 of 48 samples
      collected at 0.4 km, 8 of 24 samples collected at 0.8 km, 5 of 24 samples
      collected at 1.3 km, and 3 of 84 samples collected at > 1.7 km from the facility.
      Two samples collected at 0.8 km contained genetically diverse variants of PRRSV.
      Swine bioassays revealed the virus in flies was infectious. CONCLUSIONS AND
      CLINICAL RELEVANCE: Flies appeared to become contaminated with PRRSV from
      infected pigs and transported the virus > or = 1.7 km. Fly-born transmission may
      explain how PRRSV is seasonally transported between farms.

PMID- 15478780
TI  - Effects of exchange of dietary medium chain triglycerides for long-chain
      triglycerides on serum biochemical variables and subjectively assessed well-being
      of dogs with exocrine pancreatic insufficiency.
AB  - OBJECTIVE: To test the hypothesis that exchange of medium-chain triglycerides
      (MCTs) for long-chain triglycerides (LCTs) in the diet of dogs with well-managed
      exocrine pancreatic insufficiency (EPI) changes serum biochemical variables and
      to subjectively assess the well-being of dogs with EPI in response to
      experimental diets. ANIMALS: 21 dogs with EPI and 6 healthy control dogs.
      PROCEDURE: The effects of 3 diets containing 0%, 16%, or 35% of the total fat
      content as MCTs were examined in a randomized controlled double-blind crossover
      trial. The 3 diets were fed for 12 weeks each. Dietary effects were evaluated by
      both subjective and objective variables. RESULTS: Analysis of subjective data
      revealed no significant difference in appetite, attitude, drinking behavior,
      volume of feces, defecation frequency, color of feces, consistency of feces,
      flatulence, or borborygmus among dogs fed the 3 experimental diets. A high MCT
      content in the diet was associated with significantly higher serum vitamin E,
      cholesterol, triglyceride, retinyl stearate, retinyl palmitate, and total vitamin
      A concentrations in dogs with EPI and significantly higher serum vitamin E
      concentrations in control dogs, compared with low MCT content. High MCT content
      in the diet was also associated with significantly lower concentrations of serum
      linoleic acid (C18:2[n-6]) in dogs with EPI and in control dogs, compared with
      low MCT content. CONCLUSIONS AND CLINICAL RELEVANCE: A high MCT content in the
      diet leads to increases in serum concentrations of cholesterol and certain fat
      soluble vitamins. However, no effect was found on the subjective well-being of
      the dogs as evaluated by their owners.

PMID- 15478781
TI  - Paradigm shift: the end of "normal science" in medicine understanding function in
      nutrition, health, and disease.

PMID- 15478782
TI  - The Targ study.

PMID- 15478783
TI  - The White House Commission on Complementary and Alternative Medicine Policy and
      the future of healthcare.

PMID- 15478784
TI  - The clinical importance of vitamin D (cholecalciferol): a paradigm shift with
      implications for all healthcare providers.

PMID- 15478785
TI  - The Trager approach in the treatment of chronic headache: a pilot study.
AB  - CONTEXT: Although the traditional treatment of headache has been pharmacological,
      there have been many attempts to treat headaches with other methods with mixed
      levels of success. OBJECTIVE: To obtain preliminary data on the efficacy of the
      Trager approach in the treatment of chronic headache. DESIGN: Small-scale
      randomized controlled clinical trial. SETTING: University-based clinic. PATIENTS:
      Thirty-three volunteers with a self-reported history of chronic headache with at
      least one headache per week for at least 6 months. INTERVENTIONS: Medication only
      control group, medication and attention control group, and medication and Trager
      treatment group. MAIN OUTCOME MEASURES: Self-reported frequency, duration, and
      intensity of headache, medication usage and headache quality of life (HQOL)
      obtained at baseline and after a 6-week treatment period. RESULTS: Analyses of
      variance demonstrated significant improvement in HQOL for the Trager and
      attention control groups, and reduction in medication usage for the Trager group
      (P < 0.05). Within-group analyses revealed that participants randomized to Trager
      demonstrated a significant decrease in the frequency of headaches (P = 0.045),
      improvement in HQOL (P = 0.045), and a 44% decrease in medication usage (P =
      0.03). Participants randomized to the attention control group demonstrated a
      significant improvement in HQOL (P = 0.035) and a 19% decrease in medication
      usage (P = 0.15). Participants randomized to the no-treatment control group
      revealed a significant increase in headache duration (P = 0.025) and intensity (P
      = 0.025), and a declination in HQOL (P = 0.035). CONCLUSIONS: The Trager approach
      decreased headache frequency and medication usage. Trager and physician attention
      improved HQOL. A larger, multi-site study is recommended.

PMID- 15478786
TI  - Integrative healthcare: arriving at a working definition.
AB  - A variety of integrative healthcare programs and clinics have been initiated both
      in Canada and the United States. Many different terms (eg, integrative medicine,
      integrated medicine, multidisciplinary care, integrative health care) are used to
      describe these initiatives. The diversity of terminology and absence of a shared
      conceptual framework makes it difficult to assess when integration is actually
      happening. The objective of this paper was to explore current efforts to
      conceptualize integrative healthcare and to identify its components. A
      qualitative content analysis of articles identified in an extensive literature
      review resulted in the identification of four key components of integrative care:
      philosophy/values, structure, process and outcomes. These were used to guide the
      development of a definition of integrative healthcare that should be seen as an
      "ideal type" or goal toward which practitioners and health systems could strive.

PMID- 15478787
TI  - Sex differences in motives for use of complementary and alternative medicine
      among cancer patients.
AB  - CONTEXT: There is evidence that the prevalence of complementary and alternative
      medicine (CAM) use is increasing especially among women. However, little is known
      about why there are sex differences in the use of CAM. OBJECTIVE: This study
      investigated sex differences in motivations for use of CAM among adult cancer
      patients. DESIGN: A population-based telephone survey of CAM use. SETTINGS AND
      PARTICIPANTS: 178 male and 178 female cancer patients randomly selected from a
      statewide Cancer Surveillance System in Washington State. MAIN OUTCOME MEASURES:
      Demographics, complementary and alternative medicine use, lifestyle changes and
      four psychosocial variables: desire for personal control; internal locus of
      control; symptom distress; and perceived health status. RESULTS: Overall, 81.5%
      of women and 59.0% of men used some type of CAM. After adjusting for age and
      income, the relative odds that an alternative therapy user was female was 2.2
      (95% CI 1.4-3.3)for alternative dietary supplements, 5.0 (95% CI 2.3-11.2) for
      categories of alternative providers, 2.2 (95% CI 1.2-4.2) for focused mental
      therapies and 1.4 (95% CI 0.9-2.2) for lifestyle changes. CAM use was positively
      associated with desire for personal control among both men and women (P = 0.05).
      However, the association of two factors, dissatisfaction with a conventional
      provider and cancer-related symptom distress with alternative dietary supplement
      use, was only modestly different for men and women (P < 0.10 for interaction).
      High cancer related symptom distress score and dissatisfaction with a
      conventional provider predicted increased dietary supplement use for men, but
      decreased dietary supplement use for women. CONCLUSIONS: Clinicians should be
      aware that men and women differ considerably in their use of CAM, which may
      reflect differences in their psychological needs as they cope with their cancer
      diagnosis and treatment.

PMID- 15478788
TI  - Improving the quality of therapeutic reports of single cases and case series in
      oncology--criteria and checklist.

PMID- 15478789
TI  - Jeffrey S. Bland, PhD, FACN, CNS: functional medicine pioneer.

PMID- 15478790
TI  - Cancer care at the Sunstone Healing Center.

PMID- 15478791
TI  - Amplified fragment length polymorphism measures proportions of malaria parasites
      carrying specific alleles in complex genetic mixtures.
AB  - We are interested in developing a method for the identification of those genes in
      malaria parasites which underlie a variety of selectable phenotypes of the
      parasites including drug resistance and strain-specific immunity. A key aspect of
      our approach is to subject a genetically mixed population of malaria parasites to
      a specific phenotypic selection pressure such as the administration of an
      antimalarial drug and then identify genetic markers affected by the selection.
      Our aim, therefore, is to be able to identify those genetic markers carried by
      sensitive parasites which disappear from the population after selection as they
      should be closely linked to the locus determining the phenotype involved. We have
      previously identified more than 800 amplified fragment length polymorphisms
      (AFLP) distinguishing two cloned strains of the rodent malaria parasite
      Plasmodium chabaudi chabaudi and distributed across the whole of the parasites'
      genome. Here we evaluate the possibility that the intensities of these AFLP bands
      are quantitatively related to the proportions of parasite DNA which bear these
      markers in mixtures of genetically different parasites. We prepared mixtures of
      DNA and parasitised blood from different mixtures of two genetically distinct
      clones (AS and AJ) of P. c. chabaudi and analysed AFLP markers amplified from
      them. The results show that the relative band intensities of AFLP markers are,
      indeed, linearly related to the proportions of parasite DNA in a genetically
      mixed sample. The precision of the method is sufficient to detect reliably the
      effects of phenotypic selection at loci closely linked to a genetic locus under
      selection.

PMID- 15478792
TI  - Molecular and phylogenetic characterization of syntaxin genes from parasitic
      protozoa.
AB  - Vesicular transport is an integral process in eukaryotic cells and the syntaxins,
      a member of the SNARE protein superfamily, are a critical piece of the vesicular
      transport machinery. We have obtained syntaxin homologues from diverse protozoan
      parasites (including Entamoeba, Giardia, Trichomonas and Trypanosoma), determined
      the paralogue affinity of the homologues by molecular phylogenetics and compared
      functionally critical amino acid sites identified in other syntaxins.
      Surprisingly, three sequences deviate at the signature glutamine residue
      position, conserved in all previously identified syntaxin homologues. It is known
      that, despite conserved structure and function of both the syntaxins and the
      proteins of the regulatory SM superfamily, the various syntaxin paralogues bind
      their respective SM partners at different regions of the syntaxin molecule. These
      sites of interactions have been identified down to the individual residues. The
      pattern of conservation at these residues, in our evolutionarily diverse sampling
      of syntaxin paralogues, is therefore used to gain further insight into the
      interaction of these proteins. Phylogenetic analysis confirms and extends
      previous conclusions that the syntaxin families are present in diverse eukaryotes
      and that the syntaxin sub-families diverged early in eukaryotic evolution. This
      result is expanded with the inclusion of new homologues for previously sampled
      taxa, newly sampled taxa, and newly sampled syntaxin sub-families. Because of
      their integral role in membrane trafficking, the syntaxin genes represent a
      valuable potential molecular marker for the experimental study of the
      endomembrane system of disease-causing protists.

PMID- 15478793
TI  - Two linked genes of Leishmania infantum encode tryparedoxins localised to cytosol
      and mitochondrion.
AB  - Tryparedoxins are components of the hydroperoxide detoxification cascades of
      Kinetoplastida, where they mediate electron transfer between trypanothione and a
      peroxiredoxin, which reduces hydroperoxides and possibly peroxynitrite.
      Tryparedoxins may also be involved in DNA synthesis, by their capacity to reduce
      ribonucleotide reductase. Here we report on the isolation of two tryparedoxin
      genes from Leishmania infantum, Li7XN1 and LiTXN2, which share the same genetic
      locus. These genes are both single copy and code for two active tryparedoxin
      enzymes, LiTXN1 and LiTXN2, with different biochemical and biological features.
      LiTXN1 is located to the cytosol and is upregulated in the infectious forms of
      the parasite, strongly suggesting that it might play an important role during
      infection. LiTXN2 is the first mitochondrial tryparedoxin described in
      Kinetoplastida. Biochemical assays performed on the purified recombinant proteins
      have shown that LiTXN1 preferentially reduces the cytosolic L. infantum
      peroxiredoxins, LicTXNPx1 and LicTXNPx2, whereas LiTXN2 has a higher specific
      activity for a mitochondrial peroxiredoxin, LimTXNPx. Kinetically, the two
      tryparedoxins follow a ping-pong mechanism and show no saturation. We suggest
      that LiTXN1 and LiTXN2 are part of two distinct antioxidant machineries, one
      cytosolic, the other mitochondrial, that complement each other to ensure
      effective defence from several sources of oxidants throughout the development of
      L. infantum.

PMID- 15478794
TI  - Tegumental expression of a novel type II receptor serine/threonine kinase (SmRK2)
      in Schistosoma mansoni.
AB  - The TGF-beta family of receptor serine/threonine kinases (RSTKs) is responsible
      for a diverse array of functions in metazoans. Here, we describe the isolation of
      SmRK2, a type II RSTK expressed in schistosomula and adult stages of Schistosoma
      mansoni. Based on amino acid sequence homology, SmRK2 is most closely related to
      the Activin type II receptor subset of RSTKs. SmRK2 appears to be expressed as
      three different transcripts: one encoding a full-length receptor with 5'- and 3'
      untranslated regions (UTRs) (SmRK2), a second encoding a longer form containing
      no 3'-UTR and no stop codon (SmRK2a), and a third truncated variant (SmRK2b),
      which contains sequence encoding the first 53 amino acids of the N-terminal
      extracellular domain followed by an inserted 10 residue hydrophobic domain. Using
      an anti-peptide antibody raised against a partial extracellular domain sequence
      common to all three isoforms, SmRK2 was localized predominantly to the tegumental
      surface of the parasites. We hypothesize that SmRK2 is the receptor partner for
      the previously reported type I RSTK SmRK1 (or SmTbetaR1) and that together these
      proteins constitute a receptor system for receiving signals from the mammalian
      host.

PMID- 15478795
TI  - Gene synteny and chloroquine resistance in Plasmodium chabaudi.
AB  - Chloroquine resistance in the rodent malaria parasite Plasmodium chabaudi has
      been shown to be caused by a gene on chromosome 11, and is not linked to
      orthologues of the Plasmodium falciparum chloroquine resistance transporter
      (pfcrt) or Pgh-1 (pfmdr1) genes. In the current work, the progeny of crosses
      between chloroquine-resistant and sensitive clones of P. chabaudi have been
      analysed for the inheritance of 658 AFLP markers. Markers linked to the
      chloroquine responses of the progeny, including two which are completely linked,
      have been genetically mapped, sequenced and their homologues, or closely linked
      loci, identified in P. falciparum. The chromosome 11 markers most closely linked
      to chloroquine resistance in P. chabaudi map to loci which are also closely
      linked in P. falciparum, although in two linkage groups on chromosomes 6 and 13
      of this species. The P. falciparum orthologue of the gene conferring chloroquine
      resistance in P. chabaudi is predicted to lie within a 250 kb region of P.
      falciparum chromosome 6, containing approximately 50 genes. The genetic order of
      the markers in P. chabaudi is co-linear with the physical linkage represented in
      the P. falciparum genome database. The findings provide evidence for extensive
      conservation of synteny between the two species.

PMID- 15478796
TI  - Identification of Babesia bovis L-lactate dehydrogenase as a potential
      chemotherapeutical target against bovine babesiosis.
AB  - In this study, we characterized a novel Babesia bovis cDNA clone obtained by
      immunoscreening the cDNA expression phage library with B. bovis-infected bovine
      serum. The genetic analyses showed that it contained an open reading frame of 993
      bp, which was considered to encode B. bovis L-lactate dehydrogenase (BbLDH: E.C.
      1.1.1.27) because of the strikingly high amino acid identities of its gene
      product to the LDHs of Plasmodium falciparum and Toxoplasma gondii. Immunological
      analyses with the anti-recombinant BbLDH mouse serum showed that 36 kDa of the
      native BbLDH was expressed not only in the cytoplasm of intra- and
      extraerythrocytic parasites but also along the membrane of infected erythrocytes.
      The kinetic properties of recombinant BbLDH proved a certain enzymatic activity
      of LDH, and the activity was significantly inhibited by the addition of gossypol,
      a competitive inhibitor of protozoan LDHs. Moreover, 100 microM of the gossypol
      irretrievably arrested the in vitro growth of B. bovis. The results demonstrated
      that BbLDH provides a suitable drug target for the design of novel babesial
      chemotherapeutics.

PMID- 15478797
TI  - Dependence of Giardia lamblia encystation on novel transglutaminase activity.
AB  - Earlier, we found that three protein disulfide isomerases (PDI) from Giardia
      lamblia (gPDI) also have transglutaminase (TGase) activity in vitro. We now show
      that differentiating Giardia cells contain isopeptide bonds (epsilon(gamma
      glutamyl)lysine), the biological product of TGase activity that results in
      irreversible crosslinking of proteins in vivo. HPLC analyses showed the highest
      isopeptide bond content in cells encysting for 21 h, indicating an important role
      for TGase early in encystation. We were not able to detect isopeptide bonds in
      water-resistant cysts, possibly because they could not be extracted. One of the
      hallmarks of early encystation is the formation of encystation secretory vesicles
      (ESV) that transport nascent cyst wall proteins (CWPs) to the outer cell surface.
      ImmunoEM and live-cell immunofluorescence assays of encysting parasites revealed
      that gPDIs 1-3 are located in ESV and that gPDI-2 is also novel in that it is
      localized on the cell surface. Cystamine, a widely used TGase inhibitor, caused a
      dose-dependent inhibition of ESV formation by 21 h, thereby preventing
      development of trophozoites into cysts. Since cystamine (0.5-1 mM) inhibited the
      TGase activity of recombinant gPDIs 1-3 in vitro, PDIs appear to be the
      physiologic targets of cystamine. We found that when parasites were treated with
      cystamine, CWPs were not processed normally. These data suggest that TGase
      catalyzed reactions may be needed for either the machinery that processes CWP
      precursors or their recruitment to ESV.

PMID- 15478798
TI  - Gender-associated gene expression in two related strains of Schistosoma
      japonicum.
AB  - Host inflammatory responses directed against eggs laid by sexually-mature
      Schistosoma japonicum female worms instigate lesion formation and associated
      clinical pathologies during infection. To identify parasite gene transcripts that
      associate with egg production and to characterise sexually-mature adult gene
      expression profiles of two related Chinese strains, S. japonicum cDNA microarrays
      were fabricated using 457 ESTs originating from three parasite developmental
      stages. Twenty-two female-associated and 8 male-associated gene transcripts were
      identified in the adult Anhui strain whereas 21 female-associated and 7 male
      associated gene transcripts were revealed in the adult Zhejiang strain. RT-PCR
      analysis, in situ enzyme localisation studies and enzymatic assays confirmed the
      cDNA microarray results, and importantly, provided information previously
      unappreciated in schistosome conjugal biology. Specifically, our novel findings
      include the female-specific expression of genes putatively involved in
      haemoglobin digestion and eggshell formation including extracellular superoxide
      dismutase, two histidine-rich proteins, a large blood-brain barrier amino acid
      transporter and two tyrosinase orthologues. In contrast, transcripts involved in
      mechanical support (actin), cytoskeletal infrastructure (e.g. dynein light chain
      3 and myosin regulatory light chain) and tegumental biology (e.g. TM4SF and Sj25)
      were more highly represented in adult male schistosomes. Together these data
      establish a transcriptional basis for adult schistosome labour division and
      expands the list of novel S. japonicum gender-associated gene transcripts that
      may be considered targets for improved intervention strategies.

PMID- 15478799
TI  - Adenylate kinase and GTP:AMP phosphotransferase of the malarial parasite
      Plasmodium falciparum. Central players in cellular energy metabolism.
AB  - For coping with energetic and synthetic challenges, parasites require high
      activities of adenylate kinase (AK; ATP + AMP <==> 2 ADP) and GTP:AMP
      phosphotransferase (GAK; GTP + AMP <==> GDP + ADP). These enzymes were identified
      in erythrocytic stages of Plasmodium falciparum. The genes encoding PfAK and
      PfGAK are located on chromosomes 10 and 4, respectively. Molecular cloning and
      heterologous expression in E. coli yielded enzymatically active proteins of 28.9
      (PfAK) and 28.0 kDa (PfGAK). Recombinant PfAK resembles authentic PfAK in its
      biochemical characteristics including the possible association with a stabilizing
      protein and the high specificity for AMP as the mononucleotide substrate.
      Specificity is less stringent for the triphosphate, with ATP as the best
      substrate (75 U/mg; kcat = 2160 min(-1) at 25 degrees C). PfAK contains the
      sequence of the amphiphatic helix that is known to mediate translocation of the
      cytosolic protein into the mitochondrial intermembrane space. PfGAK exhibits
      substrate preference for GTP and AMP (100 U/mg; kcat = 2800 min(-1) at 25 degrees
      C); notably, there is no detectable activity with ATP. In contrast to its human
      orthologue (AK3), PfGAK contains a zinc finger motif and binds ionic iron. The
      dinucleoside pentaphosphate compounds AP5A and GP5A inhibited PfAK and PfGAK,
      respectively, with Ki values of approximately 0.2 microM which is more than 250
      fold lower than the KM values determined for the nucleotide substrates. The
      disubstrate inhibitors are useful for studying the enzymatic mechanism of PfAK
      and PfGAK as well as their function in adenine nucleotide homeostasis; in
      addition, the chimeric inhibitors represent interesting lead compounds for
      developing nucleosides to be used as antiparasitic agents.

PMID- 15478800
TI  - Generation and analysis of expressed sequence tags from Trypanosoma cruzi
      trypomastigote and amastigote cDNA libraries.
AB  - We have generated 2771 expressed sequence tags (ESTs) from two cDNA libraries of
      Trypanosoma cruzi CL-Brener. The libraries were constructed from trypomastigote
      and amastigotes, using a spliced leader primer to synthesize the cDNA second
      strand, thus selecting for full-length cDNAs. Since the libraries were not
      normalized nor pre-screened, we compared the representation of transcripts
      between the two using a statistical test and identify a subset of transcripts
      that show apparent differential representation. A non-redundant set of 1619
      reconstructed transcripts was generated by sequence clustering. This dataset was
      used to perform similarity searches against protein and nucleotide databases.
      Based on these searches, 339 sequences could be assigned a putative identity. One
      thousand one-hundred and sixteen sequences in the non-redundant clustered dataset
      (68.8%) are new expression tags, not represented in the T. cruzi epimastigote
      ESTs that are in the public databases. Additional information is provided online
      at http://genoma.unsam.edu.ar/projects/tram. To the best of our knowledge these
      are the first ESTs reported for the life cycle stages of T. cruzi that occur in
      the vertebrate host.

PMID- 15478801
TI  - A gene family of cathepsin L-like proteases of filarial nematodes are associated
      with larval molting and cuticle and eggshell remodeling.
AB  - Cysteine proteinases are involved in a variety of important biological processes
      and have been implicated in molting and tissue remodeling in free living and
      parasitic nematodes. We show that in the lymphatic filarial nematode Brugia
      pahangi molting of third-stage larvae (L3) to fourth-stage larvae is dependent on
      the activity of a cathepsin L-like cysteine protease (CPL), which can be detected
      in the excretory/secretory (ES) products of molting L3. Directed cloning of a
      cysteine protease gene in B. pahangi and analysis of the expressed sequence tag
      (EST) and genomic sequences of the closely related human lymphatic filarial
      nematode Brugia malayi have identified a family of CPLs. One group of these
      enzymes, Bm-cpl-1, -4, -5 and Bp-cpl-4, is highly expressed in the B. malayi and
      B. pahangi infective L3 larvae. Immunolocalization indicates that the
      corresponding enzymes are synthesized and stored in granules of the glandular
      esophagus of L3 and released during the molting process. Functional analysis of
      these genes in Brugia and closely related CPL genes identified in the filarial
      nematode Onchocerca volvulus and the free living model nematode Caenorhabditis
      elegans indicate that these genes are also involved in cuticle and eggshell
      remodeling.

PMID- 15478802
TI  - Chemical modifications of band 3 protein affect the adhesion of Plasmodium
      falciparum-infected erythrocytes to CD36.
AB  - The role of the erythrocyte anion exchanger, band 3 protein (AE1), in the
      adhesion of Plasmodium falciparum-infected erythrocytes to CD36 and
      thrombospondin (TSP) was studied. Two specific anion exchange inhibitors that
      bind covalently to different regions of the band 3 molecule affected
      cytoadherence in dissimilar ways. Modification of lysine 539 by
      diisothiocyanostilbene sulfonic acid (DIDS) resulted in a significant reduction
      in the adhesive properties of parasitized erythrocytes for CD36, but not TSP,
      whereas treatment with fluorescein-5-maleimide, which modifies lysine 430, was
      without effect on both TSP and CD36 binding. The adhesive properties of the DIDS
      binding region (DBR) was demonstrated by competition experiments using synthetic
      peptides and by direct interaction of such peptides with CD36 transfected CHO
      cells. The results suggest that host membrane proteins such as AE1 contribute to
      the adhesion of malaria-infected erythrocytes to CD36.

PMID- 15478803
TI  - RNA interference of Trypanosoma brucei topoisomerase IB: both subunits are
      essential.
AB  - Type IB topoisomerases are enzymes essential for the orderly synthesis of nucleic
      acids and are the molecular target for antitumor camptothecins. In dozens of
      organisms, including eukaryotes, bacteria, and viruses, this enzyme is monomeric.
      However, we previously found that topoisomerase IB in trypanosomes is a
      heteromultimer, comprised of two distinct subunits encoded by separate genes. A
      large 90 kDa subunit contains the DNA binding domain and a small 36 kDa subunit
      contains the catalytic domain. In this study we use RNA interference to silence
      each of the subunits separately. For each subunit, tetracycline-induced
      expression of double-stranded RNA results in drastic reduction of cognate mRNA
      and protein. For the large subunit, nucleic acid biosynthesis (as monitored by
      the incorporation of radiolabeled precursors into DNA and RNA) is halved by 39 h,
      and cell growth halts by 72 h, after induction. The steady state level of both
      nuclear and mitochondrial mRNAs is reduced. Virtually identical results are
      obtained by silencing the small subunit. Interestingly, although interference is
      specific at the level of mRNA, silencing of one subunit leads to a profound
      reduction in the level of protein for both subunits, suggesting that survival, or
      perhaps synthesis, of each subunit depends upon the presence of the other. These
      findings underscore the essential nature of type IB topoisomerase activity in
      Trypanosoma brucei and its suitability as a target for rational drug design.

PMID- 15478804
TI  - A nucleotidase with unique catalytic properties is secreted by Trichinella
      spiralis.
AB  - We have isolated and expressed a cDNA from the parasitic nematode Trichinella
      spiralis encoding a novel secreted nucleotidase which catalyses the hydrolysis of
      nucleoside 5'-diphosphates and 5'-monophosphates, but not 5'-triphosphates. The
      full length cDNA encodes a protein of 550 amino acids with an N-terminal signal
      peptide, but lacking a C-terminal signature sequence for addition of a glycosyl
      phosphatidylinositol (GPI) anchor. Expression in Pichia pastoris resulted in the
      secretion of an active enzyme with the catalytic properties of both a Mg2+
      dependent diphosphohydrolase/apyrase and a 5'-nucleotidase. The protein sequence
      is homologous to 5'-nucleotidases from a wide variety of organisms but contains
      no sequences specifically conserved in apyrases, suggesting that it is a
      representative of a new class of secreted nucleotidase. The enzyme was
      essentially monospecific for AMP among the nucleoside 5'-monophosphates and
      catalysed the hydrolysis of nucleoside 5'-diphosphates in the order of UDP >>
      ADP. The diphosphatase activity was dependent on the presence of magnesium ions
      and a reducing agent, while the 5'-nucleotidase activity was enhanced by these
      additions. Kinetic analyses indicated that the enzyme exhibits allosteric
      behaviour. Determination of the number of active sites suggested that catalysis
      of the two different reactions occurs at the same active site. The data are
      discussed in terms of regulation of host purinergic signalling during infection.

PMID- 15478805
TI  - A novel purine nucleoside transporter whose expression is up-regulated in the
      short stumpy form of the Trypanosoma brucei life cycle.
AB  - Purine nucleoside and nucleobase transporters play a vital role in the metabolism
      and survival of Trypanosoma brucei because this parasitic protozoan is unable to
      synthesize purines de novo and thus must acquire preformed purines from its
      hosts. These parasites express a variety of nucleoside and nucleobase permeases
      with diverse substrate specificities and distinct patterns of expression during
      the trypanosome life cycle. We report here that expression of the newly
      characterized T. brucei nucleoside transporter 10 gene (TbNT10) is up-regulated
      in the short stumpy form of the life cycle, the bloodstream form of the parasite
      that is pre-adapted for infection of the tsetse fly vector. Functional expression
      of TbNT10 in Saccharomyces cerevisiae reveals that the TbNT10 gene encodes an
      adenosine/guanosine/inosine transporter with apparent Km values of approximately
      1 microM and hence is a high affinity purine nucleoside transporter. The
      restricted expression of TbNT10 during the life cycle suggests that the
      functional properties of this permease may be specialized to support development
      and growth of the differentiated short stumpy form or to promote the
      transformation of short stumpy to procyclic forms within the insect vector.

PMID- 15478806
TI  - Variations in the sequence and expression of the Plasmodium falciparum
      chloroquine resistance transporter (Pfcrt) and their relationship to chloroquine
      resistance in vitro.
AB  - Chloroquine has been widely used for malaria treatment and prophylaxis for
      several decades, but its usefulness has now declined with the emergence of
      chloroquine resistance. Recent studies showed that the K76T mutation in the PfCRT
      protein, initially associated to chloroquine-resistant parasites, is sometimes
      also present in susceptible parasites, suggesting that other factors control the
      expression of the resistance phenotype. Here, we sought new mutations in the
      Pfcrt gene and used real-time PCR to investigate variations in the expression
      level of this gene with respect to the in vitro response to chloroquine. About 40
      Cambodian isolates of Plasmodium falciparum were selected on the basis of their
      response to chloroquine in vitro. The Pfcrt gene was characterised by amplifying
      and sequencing the full-length cDNA. Twelve point mutations--M74I, N75D/E, K76T,
      A144F, L148I, I194T, A220S, Q271E, N326S, T333S, I356T and R371I--were detected.
      Mutations identified at positions 144, 148, 194 and 333 had never been described
      before. These mutations define six distinct haplotypes, distributed
      heterogeneously throughout Cambodia. Only the mutations at positions 74-76, 220
      and 271 were significantly associated with the in vitro response to chloroquine.
      Three major haplotypes--MNK/A/Q, IDT/S/E and IET/S/E--accounted for all the
      isolates examined. The MNK/A/Q haplotype corresponded to susceptible isolates
      whereas parasites with the IDT/S/E haplotype displayed an intermediate response
      to chloroquine and those with the IET/S/E haplotype displayed the highest IC50
      values. Phylogenic analysis suggested that the IDT and IET haplotypes (positions
      74-76) arose independently from the wild-type MNK sequence. We found that the
      expression level of Pfcrt, evaluated by real-time PCR, had no effect on the
      response of the parasite to the drug in vitro. Similarly, in a CQ-resistant
      strain short-term cultured in the presence of CQ, no change was observed in the
      level of transcripts. These results are discussed in light of recent finding
      suggesting the possible involvement of other transporters in CQ-resistance.

PMID- 15478807
TI  - An improved chloramphenicol acetyltransferase assay for Plasmodium falciparum
      transfection.
AB  - Chloramphenicol acetyltransferase (CAT) is a popular choice as a reporter gene in
      transgenic studies in many different organisms, including Plasmodium falciparum.
      For experimental investigations into transfection efficiency and gene expression
      a robustly quantitative assay is of great value. On investigation the published
      protocol for CAT assay of P. falciparum was found to be prone to saturation due
      to the long incubation time; moreover, cellular material extracted from the
      parasite increased the enzyme activity. A new protocol was developed which is
      quantitative across a range of three orders of magnitude of CAT activity, takes
      account of the cellular extract effect, and is more rapid than the established
      method. The value of these improvements was demonstrated by analysing the effects
      of parasitaemia and amount of plasmid on transfection efficiency with both old
      and new methods.

PMID- 15478808
TI  - TbRAB23; a nuclear-associated Rab protein from Trypanosoma brucei.

PMID- 15478809
TI  - The cloning and characterisation of full-length trypsins from the salmon louse
      Lepeophtheirus salmonis.

PMID- 15478810
TI  - Synchronous invasion of host cells by Toxoplasma gondii.

PMID- 15478811
TI  - A putative neuromuscular acetylcholinesterase gene from Dictyocaulus viviparus.

PMID- 15478812
TI  - Requiem for a specialty.

PMID- 15478813
TI  - War story.

PMID- 15478814
TI  - Pediatric pathology.

PMID- 15478815
TI  - Recertification pros and cons.

PMID- 15478816
TI  - St. Paul physicians readying for surge of Hmong immigrants.

PMID- 15478818
TI  - Super-specialized.

PMID- 15478817
TI  - The power of unity.

PMID- 15478819
TI  - Emerging specialties.

PMID- 15478820
TI  - Recommended reading on the history of medical specialization.

PMID- 15478821
TI  - The origins of cardiology.

PMID- 15478822
TI  - The future of family medicine in Minnesota.

PMID- 15478823
TI  - The continuing evolution of anesthesiology in perioperative medicine.
AB  - Anesthesiology will evolve, expand, and thrive in the early 21st century.
      Exciting new capabilities, especially those associated with emerging applications
      developed by pharmacogenomic research, will provide anesthesiologists with the
      tools to increase the safety of Minnesotans, reduce pain associated with surgery
      and other procedures, and improve daily living for those with chronic pain
      disorders.

PMID- 15478824
TI  - Integrated general medical and psychiatric care: Minnesota takes the lead.

PMID- 15478825
TI  - Forecasting changes in physician services per capita in Minnesota through 2030.
AB  - As the population ages and the ratio of retirees increases, the likely supply of
      physicians and physician services over the next few decades is being closely
      scrutinized. In this article, we use simple regression models to predict the
      supply of physicians and physician-hours per capita in Minnesota through the year
      2030. We present the results from two models. The first uses data on all
      practicing physicians in the years 1995 to 2000 and projections for the entire
      population. The second "adjusted" model uses data on physicians who were younger
      than 65 in the years 1995 to 2000 and projections for the population 65 and
      older. The adjusted model represents a "worst case scenario" that removes
      physicians who typically work fewer hours from the count of physicians and
      retains the population needing the most health care services.

PMID- 15478826
TI  - Improving reimbursement: what are the options?

PMID- 15478827
TI  - Getting into gear in the off season.

PMID- 15478828
TI  - Individualised education is fairer for all.

PMID- 15478829
TI  - The next generation.

PMID- 15478830
TI  - Lost for words.

PMID- 15478831
TI  - Surviving the student years.

PMID- 15478832
TI  - The role of the Citizens Advice Bureau in supporting health care.
AB  - Increasingly, branches of the Citizens Advice Bureau throughout the UK are
      playing a vital role in supporting patients and their families, mainly through
      advising them on financial matters, but with practical and legal help on a range
      of other issues too. This new role is lifting a significant burden from health
      care staff.

PMID- 15478833
TI  - What you need to know about...jet lag.

PMID- 15478834
TI  - Increasing awareness of a rare form of haematological cancer.

PMID- 15478835
TI  - Care of the bereaved when postmortems are required.
AB  - There are two kinds of postmortem--those undertaken by coroners and those
      undertaken in hospitals. The rules for consent depend on the kind of postmortem,
      and families must be offered much fuller information than before the Alder Hey
      Inquiry. As a result, nurses need to be clear about what is involved in a
      postmortem so that they can support families in asking the right questions and
      understanding the consent issues involved.

PMID- 15478836
TI  - Evaluation of decontamination procedures used in primary care.
AB  - This study examined decontamination and infection control procedures in general
      practice. Four primary care trusts participated with a response rate of 80 per
      cent. The study showed evidence of poor compliance with national standards and
      examples of unsafe practice.

PMID- 15478837
TI  - Understanding disseminated intravascular coagulation.
AB  - Disseminated intravascular coagulation is associated with a high mortality rate,
      with patient outcomes largely dependent upon swift recognition and appropriate
      management of events. This article provides a basic overview of the condition,
      and its pathophysiology, diagnosis, treatment and nursing management, so that
      effective intervention may be implemented, maximising the chances of patient
      recovery.

PMID- 15478838
TI  - Implementing effective infection control in the hospital environment.
AB  - Preventing health care-associated infection requires a multifaceted approach.
      Although compliance with hand hygiene is the single most important factor in
      preventing cross-infection, it is important that staff and patients are aware
      that the health care environment and equipment are also potential vehicles for
      the spread of infection. Sue Wiseman explains.

PMID- 15478839
TI  - The treatment of patients with TB and the role of the nurse.
AB  - The number of reported cases of tuberculosis is on the increase. TB is a curable
      disease that usually affects the lungs and is transmitted through inhalation of
      droplets spread by coughing. Christine Bell describes how the nurse's role in the
      control of TB is vital to prevent further spread of the disease and to ensure
      that people who are affected successfully complete their course of treatment.

PMID- 15478840
TI  - The ethics of legally detaining a patient who has tuberculosis.
AB  - Patients with infectious diseases can be detained in hospitals under the Public
      Health (Control of Disease) Act 1984. Jennie Negus and colleagues reflect on a
      case that illustrates the ethical problems of implementing the current
      legislation in a hospital.

PMID- 15478841
TI  - Teaching nurses the importance of microbiology for infection control.
AB  - Ann Shuttleworth discusses whether nurses need an understanding of microbiology
      to ensure their infection control practice is effective, and whether they receive
      adequate education on the subject.

PMID- 15478842
TI  - Emergency ventilation--an alternative to mouth-to-mouth resuscitation.
AB  - The risk of infection being transmitted during mouth-to-mouth resuscitation is
      low, but health care professionals cite this as a reason for avoiding the
      procedure. Anthony Kemp discusses this issue and describes how the use of a
      pocket mask is a more acceptable alternative.

PMID- 15478843
TI  - Making the most of your student days.

PMID- 15478844
TI  - A&E gives nurses a range of skills.

PMID- 15478845
TI  - Acid-related disorders from pediatrics to geriatrics: reducing risks and
      optimizing outcomes.

PMID- 15478846
TI  - Measurement and expression of risk: optimizing decision strategies.
AB  - A significant proportion of the >6 million articles published annually present
      data in terms of risk and risk reduction. While the measurement of risk and risk
      reduction is often straightforward, there are a variety of ways that risk may be
      expressed. Risk is defined as the rate of an occurrence of a particular disease
      or adverse event and is determined by the number of events divided by the person
      years or number of individuals in the at-risk population. The portrayal of risk
      can be achieved using different techniques but is typically provided in
      demographic maps, time-trend charts, or incidence bar graphs. Risk can be
      expressed in relative terms such as relative risk or absolute measures such as
      attributable risk or number needed to treat. Understanding risk determination as
      well as the differences in risk depiction and expression is necessary to
      ascertain the relevance of the data to one's clinical practice as well as to make
      optimal clinical and pharmacoeconomic treatment decisions. A review of terms,
      together with examples, is presented, such that clinicians evaluating the medical
      literature will be able to identify differences in the way that risk-related
      results are expressed and optimize the application of such evidence to their
      practice.

PMID- 15478847
TI  - Aging, the gastrointestinal tract, and risk of acid-related disease.
AB  - It is estimated that by 2020, >16% of people in the United States will be > or
      =65 years of age and that nearly 20 million will be >85 years of age. Aging
      imparts a variety of physiologic changes in the oropharynx, esophagus, and
      stomach that increase the risk for esophageal and gastrointestinal disorders.
      Older individuals also tend to have a higher prevalence of comorbid factors, such
      as Helicobacter pylori infection, smoking, presence of other diseases, or use of
      medications (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs]) that increase
      their risk for acid-related disorders. Given these physiologic and comorbidity
      factors, the elderly are at higher risk for gastroesophageal reflux disease
      (GERD), pill-induced esophagitis, peptic ulcer disease, and complications related
      to the use of NSAIDs. Unfortunately, in the elderly patient with these disorders-
      even those with severe disease or complications--symptom presentation may be
      subtle or atypical, resulting in a delayed diagnosis. Endoscopy remains the "gold
      standard" for the identification of mucosal disease and should be performed in
      all patients with "new-onset" or persistent symptoms who are >45 years of age, as
      well as in individuals of any age who present with alarm symptoms, such as weight
      loss, vomiting, anemia, dysphagia, or evidence of gastrointestinal bleeding. In
      general, the treatment of older individuals with peptic ulcer or GERD and its
      complications is similar to that of younger individuals. Proton pump inhibitors
      are the mainstay of therapy for symptom relief, healing of erosive esophagitis,
      resolution of peptic ulceration, reduction of the risk for NSAID-induced mucosal
      damage, and prevention of disease recurrence.

PMID- 15478848
TI  - Therapeutic choices in reflux disease: defining the criteria for selecting a
      proton pump inhibitor.
AB  - Gastroesophageal reflux disease (GERD) is among the most common disorders of the
      gastrointestinal tract, with symptoms affecting a substantial proportion of the
      US population on a daily basis. Heartburn and related symptoms arise from a
      number of pathophysiologic mechanisms, including dilated intercellular spaces,
      increased duration of acid reflux, greater proximal extent of reflux, and
      esophageal sensitivity. Chronic reflux may result in serious complications, such
      as esophageal erosions or ulceration, stricture, and Barrett esophagus. The goals
      of GERD therapy are to relieve patients' symptoms and prevent complications.
      Proton pump inhibitors (PPIs) represent the most effective treatment option for
      GERD, relieving symptoms, healing erosions, and maintaining a healed mucosa.
      Differences in the pharmacokinetics and pharmacodynamics among the PPIs may
      result in differences in intragastric pH holding time as well as the onset of
      symptom relief. Lansoprazole and esomeprazole produce similar degrees and onset
      of symptom relief, with both providing greater symptom relief as compared with
      omeprazole. Although manufactured as capsules containing enteric-coated granules,
      lansoprazole, omeprazole, and esomeprazole maintain their high level of
      pharmacologic efficacy when the capsule contents are emptied into soft foods or
      various liquids. Lansoprazole and pantoprazole also are manufactured as
      intravenous formulations, and lansoprazole is available as strawberry-flavored
      granules for oral suspension and as an orally disintegrating tablet. These
      alternative routes of administration are particularly beneficial in the
      management of acid-related disorders in infants, children, the elderly, and
      patients of all ages who have difficulty swallowing or are unable to swallow
      intact capsules or tablets and those in the critical care setting.

PMID- 15478849
TI  - Gastroesophageal reflux disease: could intervention in childhood reduce the risk
      of later complications?
AB  - Gastroesophageal reflux (GER) is a ubiquitous disorder in infants. Whereas
      infants typically outgrow regurgitation by 1 year of age, the prevalence of
      gastroesophageal reflux disease (GERD) symptoms in those aged 3 to >18 years
      ranges from 1.8% to 22%. The pathophysiology of GERD in children is similar to
      that in adults. However, children may present with gastroesophageal and
      extraesophageal symptoms distinct from classic heartburn. In addition to a
      growing awareness of the high prevalence of the disorder, increasing evidence
      supports GERD being a lifelong condition in some individuals that begins in
      childhood. Although the diagnostic workup in children compared with adults may
      differ, studies suggest that the early detection and treatment of GERD in
      childhood may result in better adult disease outcomes, improved quality of life,
      and decreased overall healthcare burden. Studies of proton pump inhibitor therapy
      in children confirm high rates of mucosal healing and GER symptom resolution,
      even in children whose symptoms did not respond to H2-receptor therapy or
      fundoplication procedures. Omeprazole, lansoprazole, and esomeprazole are
      formulated as capsules containing enteric-coated granules that can be sprinkled
      onto applesauce or other soft foods. Lansoprazole is also formulated as
      strawberry-flavored granules for suspension. These as well as other alternative
      dosing formulations expand the ability to administer these agents to children.
      Moreover, long-term studies in adults and in children demonstrate that these
      agents are safe and well tolerated, even at the higher milligram per kilogram
      doses that are often required in pediatric patients because of their greater
      hepatic metabolic capacity.

PMID- 15478850
TI  - Appropriate strategies for testing and treating Helicobacter pylori in children:
      when and how?
AB  - Helicobacter pylori infection is acquired primarily during childhood and carries
      a significant lifetime risk for morbidity. In developing countries, approximately
      70% of children are infected with the bacterium by their 15th birthday. In the
      United States, the rate of H pylori infection among children varies widely-
      approximately 10% of all 10-year-olds are infected; however, this figure is
      substantially higher among populations of immigrant children and children born of
      recent immigrants to the United States. H pylori transmission is primarily
      "person-to-person" via fecal-oral, gastric-oral, or oral-oral routes, with
      evidence suggesting contaminated water as a potential source of infection. Risk
      factors for infection in childhood include an infected family member, having > or
      =2 siblings, crowded living conditions, lower socioeconomic means, and attendance
      at a daycare facility. The natural history of H pylori infection includes an
      increased lifetime risk for peptic ulcer and gastric adenocarcinoma or lymphoma.
      In children and adults who develop H pylori-related peptic ulcer, cure of the
      infection is associated with a <5% rate of ulcer recurrence. The ideal mode of H
      pylori detection among children is unclear--currently available serology and
      whole blood tests are unreliable, while the urea breath test and stool antigen
      tests have not been studied adequately. Children with confirmed H pylori-related
      peptic ulcer disease, iron-deficiency (sideropenic) anemia, or a first-degree
      relative with gastric cancer should be treated for the infection using 1 of 3
      available 10- to 14-day triple therapy regimens recommended by the North American
      Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

PMID- 15478851
TI  - Endoscopy-negative reflux disease: concepts and clinical practice.
AB  - Endoscopy-negative reflux disease is used to describe a heterogeneous group of
      disorders with symptoms that mimic those of gastroesophageal reflux disease in
      the absence of visible esophageal injury at endoscopy. Compared with patients who
      have gastroesophageal reflux-related erosive esophagitis, those with endoscopy
      negative disease are more likely to be younger, female, of lower body weight, and
      without a hiatal hernia. Approximately 50% of those with endoscopy-negative
      reflux have abnormal intraesophageal acid exposure and are considered to have
      nonerosive acid reflux disease. Those with symptoms of >12 consecutive or
      intermittent weeks' duration during the prior year, with normal acid exposure and
      without achalasia or other motility disorder with a recognized pathologic basis,
      are considered to have functional heartburn. In the absence of pathologic reflux,
      a number of etiologies may contribute to the symptoms of heartburn, including
      motor events, reflux of nonacidic gastric contents, minute changes in
      intraesophageal pH (pH <4), visceral hypersensitivity, and emotional or
      psychological abnormalities. Although persons with endoscopy-negative reflux
      disease experience decrements in their quality of life that are similar to those
      for individuals with erosive esophagitis, the response to traditional therapies
      for acid reflux may differ between the 2 groups. Studies have found that
      approximately 50% of patients with endoscopy-negative reflux disease experience
      complete symptom relief after 4 weeks of proton pump inhibitor treatment. In
      those with persistent heartburn symptoms, other structural or nonacid reflux
      etiologies for their symptoms should be explored.

PMID- 15478852
TI  - Management of acid-related disorders in patients with dysphagia.
AB  - Dysphagia affects a large and growing number of individuals in the United States,
      particularly the elderly and those who are neurologically impaired. Swallowing
      difficulties may be due to age-related changes in oropharyngeal and esophageal
      functioning as well as central nervous system diseases such as stroke, Parkinson
      disease, and dementia. Among institutionalized individuals, dysphagia is
      associated with increased morbidity and mortality. An appreciation of the
      physiology of swallowing and the pathophysiology of dysphagia is necessary for
      proper patient management. Careful history, physical examination, and evaluation
      of radiologic and endoscopic studies should differentiate oropharyngeal and
      esophageal etiologies of dysphagia and distinguish mechanical (anatomic)
      disorders from functional (motor) disorders. A significant percentage of patients
      with dysphagia have concomitant acid-related disorders that are managed best with
      proton pump inhibitor (PPI) therapy. Three of the currently available PPIs are
      manufactured as capsules containing enteric-coated granules that may be mixed
      with soft foods or fruit juices before oral administration to those with
      swallowing difficulties. In addition, omeprazole and lansoprazole may be
      administered via gastrostomy or nasogastric feeding tubes as suspensions in
      sodium bicarbonate. Novel dosage formulations of lansoprazole that may be
      appropriate for patients with dysphagia include the commercially manufactured
      lansoprazole strawberry-flavored enteric-coated granules for suspension and
      lansoprazole orally disintegrating tablets.

PMID- 15478853
TI  - Managing gastroesophageal reflux disease for the lifetime of the patient:
      evaluating the long-term options.
AB  - Lifetime management goals of gastroesophageal reflux disease (GERD) are to
      control esophageal as well as extraesophageal symptoms, maintain a stable
      noninflamed esophageal mucosa, and prevent complications. Large randomized
      clinical trials and >16 years of worldwide experience have confirmed the high
      rate of efficacy and excellent safety profile of proton pump inhibitor (PPI)
      therapy in individuals with all grades of GERD, making these agents the mainstay
      of treatment. Despite these outcomes, some individuals may desire an alternative
      to pharmacologic therapy. In such patients, laparoscopic fundoplication may
      produce symptom relief and healing of esophagitis, but its invasiveness, cost,
      and inherent surgical risks have created an interest in a variety of endoscopic
      therapies for reflux disease. Several short-term uncontrolled trials of these
      endoscopic therapies have reported encouraging preliminary results; however,
      careful patient selection as well as clinician experience is critical for their
      success. In addition to clinician expertise with the procedure, success has been
      observed only in patients with nonerosive GERD and a hiatal hernia <3 cm,
      abnormal pH monitoring, and normal esophageal motility studies, as well as in
      those who have experienced at least partial symptom relief with PPI therapy.
      Endoscopic therapy should not be considered the standard of care in patients with
      erosive disease or large hiatal hernias.

PMID- 15478854
TI  - Extraesophageal symptoms: what role for the proton pump inhibitors?
AB  - The esophageal complications of gastroesophageal reflux disease (GERD) are well
      described and include erosive esophagitis, stricture, Barrett esophagus, and
      adenocarcinoma. Primary care physicians often encounter patients with
      "extraesophageal" manifestations of GERD in the absence of heartburn. Patients
      may present with symptoms involving the pulmonary system, noncardiac chest pain,
      and ear, nose, and throat disorders. The diagnosis of reflux disease in these
      individuals may be challenging because, in addition to the absence of heartburn,
      endoscopy is often negative. Laryngoscopy and 24-hour dual-channel
      intraesophageal pH-metry may have greater diagnostic yields, but they are costly,
      invasive, and time-consuming. A trial of proton pump inhibitor (PPI) therapy is
      increasingly being considered a first-line diagnostic test in those with
      suspected reflux-related extraesophageal symptoms. The duration as well as dose
      of PPI should be based on the presenting symptoms, with patients having pulmonary
      manifestations often requiring twice-daily therapy for 2 to 3 months. In
      contrast, symptoms of reflux-related noncardiac chest pain may be relieved with a
      1-week, standard-dose treatment trial. Patients who fail to experience symptom
      resolution or improvement should undergo further diagnostic evaluations including
      24-hour esophageal pH studies while continuing their PPI therapy to establish
      persistent versus absent acid reflux. The role of fundoplication or other
      surgical/laparoscopic procedures in these patients has yet to be determined.

PMID- 15478855
TI  - Prevention of nonsteroidal anti-inflammatory drug-associated gastrointestinal
      symptoms and ulcer complications.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) produce symptoms of dyspepsia and
      peptic ulcer disease in up to 50% and up to 20%, respectively, of individuals
      taking them. Risk factors for NSAID-related gastric injury include age >70 years,
      history of ulcer disease, use of multiple agents (e.g., > or =2 NSAIDs, or an
      NSAID plus aspirin--even at cardioprotective doses), high doses of an NSAID, and
      concurrent use of corticosteroids or anticoagulants. In NSAID users, infection
      with Helicobacter pylori can produce additive or synergistic gastric mucosal
      injury. Several clinical strategies can decrease the risk for dyspepsia,
      ulceration, and the more serious complications in NSAID users. Proton pump
      inhibitor (PPI) co-therapy has been shown to lower the incidence of dyspepsia in
      those taking NSAIDs. In those with an active ulcer, PPI therapy produces ulcer
      healing even in "tough-to-treat" individuals who require ongoing NSAID therapy.
      Maintenance of ulcer healing is significantly greater in those who receive
      ongoing PPI treatment compared with placebo, and adverse events and treatment
      withdrawals are fewer compared with their occurrence in persons treated with
      misoprostol. In those not receiving aspirin therapy, the use of an NSAID that is
      a selective inhibitor of cyclooxygenase (COX)-2 may result in fewer
      gastrointestinal symptoms compared with a traditional agent; however, studies
      have failed to show any decrease in healthcare resource utilization (including
      outpatient or emergency room visits, hospitalization rate, or use of any
      resource) with COX-2-selective therapy.

PMID- 15478856
TI  - Cardioprotective effects and gastrointestinal risks of aspirin: maintaining the
      delicate balance.
AB  - Aspirin is a very useful medication for the prevention of cardiovascular
      thrombotic events in patients with or those at risk for cardiovascular disease
      (CVD). Aspirin, however, carries an increased risk for gastrointestinal (GI)
      injury (e.g., ulceration) and its complications (e.g., hemorrhage), which may be
      caused by its antiplatelet and gastric mucosal effects. In those with established
      CVD, aspirin use has been documented to decrease the risk of a first myocardial
      infarction (MI). Its effects on stroke and vascular death are less conclusive.
      The use of aspirin in these individuals is recommended only for those whose risk
      for cardiovascular events (based on coronary risk assessment tools) is
      sufficiently high that it outweighs the risk for GI complications. Secondary
      prevention refers to the use of aspirin to prevent cardiovascular events in
      patients with established CVD such as an MI, stroke, or angina. The use of
      aspirin in these individuals is recommended based on a documented decrease in
      future cardiovascular events and mortality. The risk for GI events with aspirin
      is at least additive to the risk for these events in those who also are receiving
      therapy with a nonsteroidal anti-inflammatory drug. Patients being treated with
      aspirin, even at 81 mg/day for cardioprotection, should be assessed for factors
      that increase the risk for GI injury. Studies have confirmed that co-therapy with
      a proton pump inhibitor (PPI) or misoprostol decreases the risk for GI injury and
      complications. Although both classes of such gastroprotective agents are
      effective, treatment with a PPI is tolerated better, with fewer patients
      discontinuing the drug because of side effects such as diarrhea.

PMID- 15478857
TI  - Barrett esophagus: will effective treatment prevent the risk of progression to
      esophageal adenocarcinoma?
AB  - Barrett esophagus is a complication of long-standing gastroesophageal reflux
      disease (GERD) and is the well-recognized premalignant condition for the majority
      of esophageal and gastroesophageal junction adenocarcinomas. Although duration of
      gastroesophageal reflux (GER), male sex, and, possibly, a strong family history
      are directly related to risk of Barrett esophagus, the role of screening in those
      with GERD and surveillance in those with confirmed Barrett syndrome remains
      controversial. Acid suppression with proton pump inhibitor (PPI) therapy plays a
      pivotal role in the management of symptoms in persons with chronic GER and
      Barrett esophagus. Although there is no conclusive evidence for the role of PPIs
      in regression of Barrett epithelium or prevention of dysplasia, longer-term
      studies that titrate the dose to normalization of esophageal pH may proffer
      different data in the future. Although highly touted in the literature, surgical
      and endoscopic ablation therapies are limited by several factors, including high
      rates of symptom recurrence, persistently abnormal pH values, need for repeat
      surgery, and, in the case of endoscopic therapy, residual Barrett metaplasia that
      can progress to high-grade dysplasia or cancer. These invasive interventions
      should only be considered after consultation with a gastroenterologist. Cancer
      chemoprevention strategies are just emerging, and their roles as direct
      chemoprotectants remain to be determined.

PMID- 15478858
TI  - Will eradication of Helicobacter pylori infection influence the risk of gastric
      cancer?
AB  - Gastric adenocarcinoma is a disease of high mortality and poor prognosis that is
      second only to lung cancer as a leading cause of cancer-related deaths worldwide.
      Although gastric cancer has a multifactorial etiology, infection with
      Helicobacter pylori is highly associated with its development. New information on
      bacterial and host genetics and results of epidemiologic studies suggest that
      better identification of individuals at high risk for gastric malignancy may be
      possible. Studies suggest that cure of H pylori infection may be associated with
      retardation of glandular atrophy and intestinal metaplasia but not reversal of
      dysplasia. Theoretically, it is attractive to believe that eradication of H
      pylori infection might prevent gastric cancer; however, studies supporting this
      hypothesis are not yet available. Public policy strategies for the identification
      of patients at risk for H pylori-related gastric malignancy are likely to be
      complex, but testing and treating for the infection earlier rather than later in
      life is anticipated to be the more beneficial approach.

PMID- 15478859
TI  - Assessment of neutrophil components as markers of lung injury in the course of
      bovine respiratory tract infections.
AB  - To define the role of activated neutrophils in lung injury during bovine
      respiratory tract infections (BRTI) their in vitro function was investigated. As
      a means to achieve this goal the comparison of secretory action between
      neutrophils from the BRTI group and control was made on the basis of elastase,
      myeloperoxidase (MPO), alkaline phosphatase (ALK-P) release, and nitric oxide
      production. We noted that there is an interdependence between secretory response
      of neutrophils and clinical severity of BRTI. The release of elastase was greater
      in the BRTI group than in the control group (49.17+/-4.41 versus 46.43+/-4.95% of
      the total content). Neutrophils from infected heifers exhibited a significantly
      (p<0.05) higher value of MPO release than from healthy heifers and reached
      39.23+/-10.18 versus 25.54+/-8.41% of the total content. ALK-P containing
      granules released significantly (p<0.001) more enzyme in the group with BRTI than
      in the control group (22.42+/-6.27 versus 13.74+/-2.01% of the total enzyme
      content). The level of nitrite accumulation rose in the culture of cells isolated
      from heifers with BRTI from 4+/-0.53 microM after 0.5h to 6.9+/-0.52 microM after
      72 h. Our data suggest that during BRTI the increase of neutrophil secretory
      action results in augmentation of enzyme release including elastase, MPO and ALK
      P, and the nitrite production. During an excessive secretory response of
      neutrophils all these factors contribute to lung injury and worsen the course of
      a disease and might be recognised as markers of lung injury. Moreover, such a
      destructive action of neutrophils must be taken into account during the
      introduction of new methods of BRTI treatment.

PMID- 15478860
TI  - Immunocytochemical identification of neoplastic cell clone in phase S of cell
      cycle in transplantable rat tumors.
AB  - Wistar and Buffalo rats of both sexes, aged 4 months, were divided into three
      groups: I which was given an intramuscular injection of 3 x 10(6) cells of Morris
      hepatoma (Buffalo males), II--subcutaneous injection of 3 x 10(4) cells of
      mammary gland carcinoma (Wistar females), III--intraperitoneal injection of 3 x
      10(4) cells of Yoshid sarcoma (Wistar males). The animals were killed: in group I
      -19, group II--13 and in group III--6 days after tumor transplantation. Twenty
      four hours before euthanasia the rats were given 5-brome-2'-deoxyuridine (BRd-U)
      at a dose of 50 mg/kg body mass. The control group consisted of animals with
      tumour. They were not treated with BRd-U. Immunocytochemical reaction was
      performed on the sections of tumors, using monoclonal anti-BRd-U clone BU-33,
      Sigma. Computer measurements of tumor cells were carried out. There was a high
      similarity in morphological parameters between two kinds of cancer, and clear
      differences between them and Yoshid sarcoma. The main difference was noted in a
      twofold increase in the quantity of synthesised DNA in the nuclei of sarcoma
      cells. Immunocytochemical identification of tumor cells in phase S of the cell
      cycle with the use of monoclonal anti-BRd-U antibody is a precise and quick
      method of estimation of their proliferative potential.

PMID- 15478861
TI  - Influence of various treatment methods on bacteriological findings in cows with
      puerperal endometritis.
AB  - The aim of the study was to identify the species of microorganisms isolated from
      the uterus of healthy cows (control group) and cows affected with puerperal
      metritis (PM) before and after an experimental therapy with an immunomodulator
      and antibiotics versus commonly applied methods (antibiotic + beta-blocker or
      antibiotic + PGF2alpha). Examinations were carried out on 110 cows with PM in
      three farms with similar system of rearing and nutrition. The control group
      consisted of 21 cows without postpartum disturbances. Smears from the uterus were
      taken before treatment and then at 21st day of observation. Escherichia coli and
      other species of Enterobacteriaceae family were isolated from 48.2% of PM cows
      and 47.6% of healthy cows. The degree of Arcanobacterium pyogenes infection was
      statistically lower in healthy than in sick cows (9.5% versus 30.0%).
      Streptococcus sp. was isolated from 13.6% of PM cows and from 16% of control
      ones. Staphylococci were isolated from 10% of PM and from 30% of control cows.
      Other bacteria species were isolated from about 10% of the examined cows. The
      best elimination of infections (66%) was noted in cows treated with the
      intrauterine antibiotic in combination with PGF2alpha i.m. injection. Examination
      showed that species of bacteria in the postparturient uterus were similar in
      healthy and sick cows. However, Arcanobacterium pyogenes was isolated 3 times
      more often from the sick animals. This pathogen was identified in 11 cows out of
      19 (57.9%) culled subsequently because of infertility after the metritis
      puerperalis was clinically cured.

PMID- 15478862
TI  - Influence of zearalenone micotoxicosis on selected immunological, haematological
      and biochemical indexes of blood plasma in bitches.
AB  - The immunological, haematological and biochemical analyses of blood plasma in
      bitches with 50 days lasting induced zearalenone micotoxicosis were carried out.
      It can be indirectly suggested that the inhibition of the humoral reaction of the
      organism, stimulation of detoxification effect in the liver and decreased
      cellular answer took place.

PMID- 15478863
TI  - Modification of zearalenone structure in model and natural conditions.
AB  - Zearalenone is a mycotoxin widely occurring in cereals and animal feed, and it is
      associated with hyperestrogenism and other reprodutive disorders in animals. A
      new method of detoxication of feedstuffs involves alkaline hydrolysis of toxic
      macrolactone (1) (as well as model compounds (2a, 2b)). The method caused
      modification of zearalenone structure under mild conditions and the toxin
      underwent irreversible hydrolysis with high efficiency.

PMID- 15478864
TI  - Metabolic profile of pigs fed feed containing zearalenone destructor.
AB  - Zearalenone (ZEA) is a member of macrocyclic lactons family. It is a toxin-
      phytosteride produced by fungi of Fusarium ssp. genus. Zearalenone contaminates
      food and animal feeding stuffs and its destruction is difficult. It requires
      application of particular compounds that would bind zearalenone in the feed or
      feeding stuff or in the gastrointestinal tract and decrease its bio
      accessibility. It should also fulfil all the safety requirements regarding the
      plant supplements and animals that are fed with this feed. The aim of the study
      was to estimate if the feed supplemented with different doses of zearalenone and
      zearalenone destructor causes changes of the metabolic profile in gilts. The
      results obtained show that applied destructor did not cause negative
      haematological and biochemical changes in the blood of the gilts examined. It can
      be suggested that it is a safe feed supplement pigs in prevention of zearalenone
      micotoxicosis.

PMID- 15478865
TI  - The Canine Parvovirus wild-type strains infections in dogs--epidemiological and
      diagnostic aspects.
AB  - Biological material was taken from dogs with diarrhea. Faecal samples were taken
      from live animals white intestinal tract fragments (i.e. small intestine, and
      stomach) were taken from dead animals. In total, 18 specimens were investigated
      from dogs housed alone or in large groups. The samples were examined for presence
      of viral infections and concurrent bacterial and parasitic infestations. To test
      for the presence of the viral infection, latex (On Site Biotech, Sweden) and
      direct immunofluorescence tests were performed. At the same time to the presence
      of CPV infection, was conducted by the PCR method with primers complementary to a
      conservative region of VP1/VP2. In order to identify the bacterial strain, the
      material was inoculated onto appropriate media and identified with API tests,
      whilst parasitological examinations were performed with Fulleborn's method. CPV
      infection was accompanied by CCV and CAV infections, as well as bacterial ones,
      caused mostly by Escherichia coli.

PMID- 15478866
TI  - The distribution and chemical coding of neurons in the celiac-superior mesenteric
      ganglion complex supplying the normal and inflamed ileum in the pig.
AB  - The present study investigated the chemical coding of neurons in the celiac
      superior mesenteric ganglion complex supplying the normal (n=4) and inflamed
      (n=4) ileum (chemically-induced inflammation) in juvenile pigs using retrograde
      tracing combined with immunohistochemistry. Ileum-projecting neurons (IPN) were
      predominantly distributed in the left and right superior mesenteric pools of the
      ganglion. The majority of them were adrenergic (tyrosine hydroxylase-positive)
      and also contained neuropeptide Y, somatostatin or galanin. No clear-cut
      differences in the distribution and chemical coding of IPN were found between
      normal and inflamed pigs. However, in the inflamed group, the density of
      peptidergic, IPN-associated nerve fibres was higher than that found in the
      control group.

PMID- 15478867
TI  - Occurrence of Lawsonia Intracellularis and Brachyspira spp. infection in swine
      suffering from diarrhoea.
AB  - Principal aim of this study was to examine fecal samples from pigs suffering from
      diarrhea for the presence of Lawsonia intracellularis, Brachyspira hyodysenteriae
      and Brachyspira pilosicoli. The molecular techniques such as PCR and nested PCR
      were employed to detect the presence of p78 fragment of genomic DNA specific for
      Lawsonia intracellularis as well as fragment of tlyA gene specific for
      Brachyspira hyodysenteriae and 16S rDNA gene of Brachyspira pilosicoli. We
      assumed that about 25% of pigs were infected with Lawsonia intracellularis, about
      10% with Brachyspira hyodysenteriae and only 0,8% with Brachyspira pilosicoli. In
      about 3% mixed infection with L. intracellularis and B. hyodysenteriae was
      observed. Results were comparable in herds that differed in quantity, breeding
      technology, hygienic standards and preventive treatment with different
      chemotherapeutics.

PMID- 15478868
TI  - Microbiological quality of petfood in Poland.
AB  - From epidemiological and safety point of view, petfoods produced from edible and
      non-edible animal by-products should be safe for slaughter animals, owners of
      these pets and environment. Domestic animals are recognized as highly important
      reservoir of pathogenic microorganisms for man. The close contact of people and
      especially children with pets may constitute a serious hazard for their health.
      Taking these aspects into account, the study was undertaken in which 2271 dried
      and 18 canned petfood samples were examined. Moreover, 14, 90, 23 and 22 samples
      of petfoods were examined for presence or number of Clostridium sp.,
      Enterobacteriaceae, total plate count, and yeast and moulds, respectively.
      Salmonella was isolated from 22 (1%) out of 2271 dried petfood samples examined.
      Number of Enterobacteriaceae was higher than 300 cfu/g, i.e. the allowed maximum
      level was found in 9 (10%) samples examined. The rest of microbiological quality
      parameters did not exceed the allowed values.

PMID- 15478869
TI  - Limits and regulations for mycotoxins in food and feed.
AB  - Mycotoxins are natural contaminants whose presence in food- and feedstuffs cannot
      be completely avoided. Since several mycotoxins have been associated with and
      implicated in human and animal diseases there is a need to establish maximum
      levels, guidelines or action levels for them in some kinds of commodities.
      International and government authorities in many countries have been investing in
      mycotoxins research and initiating administrative actions for elaboration of
      legislation and implementing regulatory measures for the control of mycotoxins.
      Codex Alimentarius Commission is established international legislation on food
      and feed. In European Union specific limits and regulations for mycotoxins and
      other contaminants are constructed under the general Codex standards and based on
      proposal from European Commission. The legal basis for European Commission became
      available with the framework Council Regulation (EEC) No 315/93. In this paper,
      legislation regarding maximum levels for certain mycotoxins in food- and
      feedstuffs in European Community and other countries were reviewed and discussed.

PMID- 15478870
TI  - National programme of official control of animal feedingstuffs under surveillance
      of veterinary inspection in Poland.
AB  - Poland as a new EC country is obliged in agree with Directive 95/53/EC to drawn
      up one, coherent and coordinated national programme of official inspection,
      irrespective of the organisational structure, and the number of inspection
      authorities in a country. Taking these facts into account the author has worked
      out the Polish National Programme of an official control conducted by the
      Veterinary Inspection in the field of animal feedingstuffs sector in Poland. The
      objective of the programme is to lay down the substantive scope of official
      inspections and laboratory control testing of animal feedingstuffs, appropriate
      for the surveillance exercised by the Veterinary Inspection. The programme is
      under implementation process which has begun in 2004.

PMID- 15478871
TI  - The effect of phytoestrogens on the reproductive tract.
AB  - Environmental estrogens may be derived from plants (phytoestrogens),
      pharmaceuticals or synthetic compounds. They exert estrogenic and/or potentially
      antiestrogenic effects on farm animals, wildlife and humans. Exposure to these
      compounds results in some abnormalities in the reproductive tract, changes in the
      estrous cycle, and possibly protection against the development of hormone
      dependent cancer. The data obtained from animal studies suggest that the timing
      of exposure to phytoestrogens is important, and neonatal exposure causes the most
      pronounced effects.

PMID- 15478872
TI  - Use of natural and synthetic aluminosilicates in decontamination of feed
      contaminated by fungi and micotoxins.
AB  - The contamination of feed with micotoxin has been a serious problem in animal
      nutrition. Many existing methods of decontamination are not satisfying due to the
      toxicological safety and health quality of the fodder materials. It stimulates
      the scientists to search for the new methods. The use of sorbents in the form of
      natural and synthetic aluminosilicates is a promising direction. The efficacy of
      aluminosilicates towards aflatoxins has been proved. However, their influence on
      other micotoxins is not that obvious. According to the last investigations, the
      use of aluminosilicates in nutrition does not cause any side effects and
      widespread pathological effects are observed only when dosage is incorrect.
      Regarding the analyses that were published, it can be supposed that the addition
      of several different aluminosilicates is a sufficient protection against
      mycotoxicoses.

PMID- 15478873
TI  - Role of antioxidants in the protection against oxidative stress in cattle--trace
      elements and enzymatic mechanisms (Part 3).
AB  - The most important enzymatic mechanisms which protect an organism against
      oxidative stress are superoxide dismutase (SOD), peroxidase (Px), e.g.
      glutathione peroxidase (GSH-Px) and ascorbate peroxidase, catalase and
      glutathione reductase. Their activity depends on many trace elements. Enzymatic
      mechanisms, functioning under physiological conditions, prevent the spread of
      free radical reactions. New and reoccurring metabolic and infectious diseases of
      cattle emerge when there is a disproportion in the balance between reactive
      oxygen species and antioxidative enzymatic barrier.

PMID- 15478874
TI  - Utilization management for residential programs.
AB  - This paper reviews recent literature on utilization management (UM) in community
      based supportive residential programs for people with behavioral disorders.
      Various approaches for facilitating placement and movement are discussed in the
      context of an effort to develop a residential UM process in New Haven,
      Connecticut. Recommendations are made for a residential UM process that may be
      applied to a range of service systems. It takes into account the methodological
      difficulties inherent in the development of generalizable decision tools.

PMID- 15478875
TI  - Decreasing the use of mechanical restraints and locked seclusion.
AB  - This article describes attempts by an inpatient unit, treating adolescents with
      developmental delays and with severe psychiatric disturbances, to reduce its use
      of physical restraints. This restraint reduction process involved two phases: (1)
      assessment and (2) systems intervention. The assessment phase consisted of
      extensive observations of staff response to patient crises, staff interviews,
      patient interviews, and the development of a data-tracking system for restraint
      and seclusion (R/S) usage. Multiple contributing factors were identified during
      the assessment phase that increased R/S usage. The second phase, organizational
      and clinical intervention, included staff education and training, treatment
      interventions, and system changes aimed at reducing R/S usage. R/S reduction data
      over the course of the project are presented.

PMID- 15478876
TI  - Consumer satisfaction with inpatient mental health treatment in the Department of
      Veterans Affairs.
AB  - This study used hierarchical linear models to analyze post-discharge data among
      17,130 veterans who received inpatient VA mental health services between 1995 and
      2001, in order to determine whether changes in mental health service affected
      inpatient satisfaction. In models without covariants, half the satisfaction
      measures increased while the other half indicated no significant change. After
      adjusting for changes in patient characteristics, however, nine measures
      indicated no change and seven showed significant declines. Demonstrating the
      importance of risk-adjustment, satisfaction appeared to increase over time prior
      to risk adjustment, but declined after adjusting for changes in patient
      characteristics that were associated with patient satisfaction.

PMID- 15478877
TI  - Talk about costs: health care professionals' views about expenses related to
      substance abuse treatment.

PMID- 15478878
TI  - Political dominance of mental health services in the People's Republic of China.

PMID- 15478879
TI  - Xenotransplantation--will it bring the solution to organ shortage?
AB  - Xenotransplantation, the transplantation of organs, tissues and cells from
      animals, preferably pig-to-man, might be considered to become the transplantation
      of the future. Organs from domestic animals are available in unlimited numbers
      for xenogeneic transplantation and could swiftly solve the problem of organ
      shortages. Domestic animals of about the same size as human beings would be ideal
      organ sources. By selective breeding the anatomical and some physiological
      characteristics of these animals could be at least partly adapted to match the
      human body. However, the immunological mechanisms and the antigenicity of cells
      and their surface structures will remain obstinately unaltered. The only hope is
      that wide-reaching transgenic manipulation of animals, will soon achieve great
      changes in immunological and physiological circumstances.

PMID- 15478880
TI  - An overview of legal aspects in organ transplantation--what are the family
      rights?
AB  - A short review of legal aspects of organ transplantation. The influence of type
      of consent and the family attitude on organ donation rate in all European
      countries. A special attention is given to the legal and ethical aspects of
      living organ and tissue transplantation.

PMID- 15478881
TI  - National donor registers. A worldwide survey.
AB  - Donor registers where individuals can register their attitudes on postmortem
      donation are now in operation in a large number of nations and states. Donor
      registers are being considered in some other states. It can be expected that
      there will be new registers. Information on existing registers will be needed to
      guide decision-makers. The term donor register will be used in this presentation
      in spite of the fact that it is a misnomer and may be misleading. There are
      registers where you can register as a donor; there are registers where you can
      indicate that you object to being a donor. Moreover there are combinations of the
      two types and besides, there are registers where you indicate that someone else
      has to approve of your decision or has to be consulted. Since donor registers are
      all different it is not within the scope of this paper to give detailed
      information on any one of them. Instead general information will be given on
      existing donor registers in various parts of the world. References will be given
      to evaluations and review papers. Suggestions will be given for a state of the
      art donor register and some questions with no obvious answers will be discussed.

PMID- 15478882
TI  - How to improve organ donation in the MESOT countries.
AB  - There are more than 29 countries that have membership of the Middle East Society
      for Organ Transplantation (MESOT) with more than 600 million populations. These
      include all Arab countries, Iran, Turkey, Pakistan and countries of Central Asia.
      There are common features of organ transplantation in the Middle East Countries
      that include inadequate preventive medicine, uneven health infrastructure, poor
      awareness of the medical community and public at large of the importance of the
      organ donation and transplantation, high level of ethnicity and poor government
      support of organ transplantation. In addition, there is lack of team spirit among
      transplant physicians, lack of planning for organ procurement and transplant
      centers and lack of effective health insurance. Patients seek commercial
      transplantation most of the time. Patients on waiting lists for organ
      transplantation increase with time and there is a considerably growing gap
      between supply and demand of organs in the MESOT countries. Living organ donation
      is the most widely practiced type of donation in the Middle East and includes
      kidney and partial liver. Cadaver organ donation has a great potential in the
      Middle East. Nevertheless, this source is still not utilized properly due to the
      continued debate in the medical community about the concept of brain death and
      inadequate awareness of the public of the importance of organ donation and
      transplantation in many countries in this region.. There are three dominant and
      distinctive models for practice including the Saudi, Iranian and Pakistani
      models. The Saudi model includes the presence of a national organ procurement
      center as a governmental agency to supervise organ donation and transplantation.
      The Iranian model consists of renal grafts donation from the living genetically
      unrelated persons to the benefit of patients with end-stage renal disease. The
      Pakistani model is an interesting funding model for management of end-stage organ
      failure in the developing countries. We conclude that organ donation and
      transplantation are hampered with obstacles in the MESOT countries. Solutions
      need continuous work on many fronts. Local experiences can be implemented into
      new improved models that can help overcoming current obstacles.

PMID- 15478883
TI  - Incentives for organ donation: some ethical issues.
AB  - Objections to commerce in organs has not stopped the spread of such practice
      around the world. In most countries the gap between supply and demand for organs
      continues to increase. Kidneys from living donors are considered a valuable
      addition to the donor pool, and in a more acquisitive world, donor incentives are
      becoming thinkable, even acceptable. Current incentives for cadaver and living
      organ donation are reviewed from ethical and legal perspectives. A new principle
      of reimbursement for the living donor's risk and pain is defined and presented
      for debate.

PMID- 15478884
TI  - Financial incentives for cadaveric organ donation.
AB  - One of the main obstacles of organ transplantation all over the world is the
      insufficient number of available cadaveric organs. Various attempts are
      considered to increase the consent rate. Financial incentives as a possibility to
      raise the number of procured organs is a very controversial topic. Arguments for
      and against financial incentives are presented as well as the different models.

PMID- 15478885
TI  - The Australian experience in organ donation--2003.
AB  - The Australian performance in deceased donor organ donation continues to languish
      near the bottom of the International ladder. This is despite a national
      expenditure on health 10% more than the average OECD country (dollars per capita)
      and the presence of active transplantation programs (heart, kidney, liver, lung
      and pancreas) with excellent success rates. The deceased donor rate has fallen
      from 14 donors pmp in 1989 to 9 at the present time and appears to be still
      falling. Living donors now outnumber deceased donors as a source of kidney
      transplants. Causes of the low deceased donor rate appear to include variable
      management of severe brain injury, shortage of ICU beds, lack of ICU priority to
      potential donors when beds are restricted, and a low family consent rate (50%)
      despite 83% of the public being willing to donate. Programs aimed at addressing
      these issues are planned and include additional funding for beds, improved
      identification of donors and a standard pathway for managing severe brain injury.

PMID- 15478886
TI  - Cadaveric & living organ donation. Natural limitations. Possible solutions.
      Singapore experience.
AB  - Singapore is a country with different cultures and beliefs. Over the last thirty
      eight years since independance, it has blossomed close to being a developed
      nation. Having performed the first cadaver donor renal transplantation in 1970,
      there has been a tremendous amount of health literacy injected into the
      Singaporeans, with the able support of the National Kidney Foundation. Never
      ending waiting list for organ donation has facilitated a march of events from
      Volunatary Organ Pledging under the Medical Therapy, Education and Research Act
      to passing the Human Organ Transplant Act to extension of the presumed consent
      law to include Heart, Liver and Cornea and non-accidental brain deaths. In the
      years to come, Singapore will certainly see an increase in the number of organ
      transplantations both Cadaveric and Living related.

PMID- 15478887
TI  - The COPe concept for the training of communication in highly emotional
      situations.
AB  - Members of transplant teams are oft confronted with highly emotional situations.
      Inability to handle these situations leads to burn-out and impairs the
      performance of the team. We introduce and discuss first experiences with a
      training program--COPe--specifically concentrating on establishing and
      maintaining communication in such situations.

PMID- 15478888
TI  - The role of education in increasing organ donation.
AB  - The influence of extensive educational programs in increasing organ donation is
      discussed. Improvements in organ donation rates can be expected by acceptance of
      the "suboptimal donor", economic assistance to those responsible for organ
      procurement and the information campaigns for the general public. Organ shortage
      can be considered as a "disease" that kills thousands of persons yearly.
      Educational programs are discussed.

PMID- 15478889
TI  - Organ shortage, are we doing our best?
AB  - Continuing organ shortage and ever-longer waiting lists have prompted the
      transplant community to adopt a broader than medical perspective in attempts at
      increasing the donor pool. Surveys conducted in various parts of the world reveal
      only a moderate acceptance of transplantation among medical professionals, a
      possible consequence of inadequate educational program at school/university
      level. General public awareness is low and efforts should be aimed at promoting a
      philosophy of sharing, reevaluating the traditional notion of the integrity of
      the human body, encouraging a readiness to fullfil an ever present social need
      through organ donation. Educational undertakings, in the long run, should modify
      the behaviour of society in making it better-informed and more sharing-oriented.

PMID- 15478890
TI  - The effect of The World Transplant Games on transplant rates in five continents.
AB  - This paper outlines the effect that the Transplant Games have had in influencing
      public opinion and the translation of that effect resulting in increased organ
      donation and transplantation in the global venues in which this activity took
      place. A brief account of the history of the Transplant Games now 25 years after
      its inception is given. The ancillary steps which, over this period of time, have
      been found valuable in achieving a significant increase in organ donation are
      outlined. The positive effect of this sporting activity as an aid to the
      physical, psychological and social rehabilitation of previously debilitated
      individuals is discussed.

PMID- 15478891
TI  - Quality and safety of organ transplantation.
AB  - Transplantation, like all medical procedures, carries potential risks for both
      donors, recipients and health care personnel. Living donation and associated
      morbidity and mortality are documented in living donor registries which, run
      nationally, are a step toward long-term quality control in organ transplantation.
      Such quality control and management should however be a part of all stages of the
      transplantation process, beginning with donor identification and ending with long
      term follow up of transplant recipients. A whole range of transplantation-related
      events would be controlled, including organ procurement, handling, risk of
      disease/malignancy transmission, recipient operation and follow up. Several
      international bodies and institutions have formulated statements addressing these
      issues. The essential ideas of these documents are focused on protection of human
      integrity, avoidance of bodily harm and coercion, exclusion of commercialism,
      equitable access to transplantation, fairness of allocation, transparency of the
      allocation criteria/procedures, competence requirements of the staff and quality
      management.

PMID- 15478892
TI  - Donor transmitted malignancies.
AB  - Early experiences in transplantation, which pre-dated brain death laws, utilized
      organs from donors with active malignancies. The use of organs from such donors
      occasionally resulted in the transmission of malignancy from the donor to an
      unknowing recipient. Over a period of three decades, Israel Penn, M. D.
      catalogued some two hundred and fifty cases of organs transplanted from donors
      with a history of malignancy; carefully examining each reported case for tumor
      histology, donor risk factors, method of tumor presentation and recipient
      outcome. Some recipients never developed malignancies, while others were less
      fortunate, developing cancers that were suspicious for donor origin. The
      evolution of transplantation has resulted in improved patient survival, which in
      turn has led to an increased demand for organ transplantation. Unfortunately, the
      supply of organs available for transplantation has failed to keep pace with the
      demand, with the worldwide deficit growing annually. In an effort to bridge the
      widening gap, utilization of older and more marginal donors has been suggested.
      However, use of older donors is accompanied by the likelihood that a significant
      proportion may have undiagnosed malignancies. Multiple transplant programs have
      considered the use of donors with tumors of non-malignant or even low-grade
      malignant histology, most often involving the central nervous system (CNS).
      According to a survey from the United Network for Organ Sharing (UNOS), central
      nervous system malignancies are among the most commonly identified malignancies
      found in potential donors. This study examines the distribution of potential
      donor transmitted malignancies reported to the Israel Penn International
      Transplant Tumor Registry. The incidence of tumor transmission is examined in the
      overall group as well as among individual histologies. We also seek to identify
      specific factors associated with the risk of malignancy transmission from donor
      to recipient, in an effort to minimize future transmission of donor tumors to
      unwitting recipients. The study is based on voluntary registry data, which some
      argue can be criticized for a lack of true incidence data. In reality, however,
      this data may provide a more accurate insight since it is based on transmissions
      from high-risk donors rather than from the general population.

PMID- 15478893
TI  - Kidney transplantation from organ donors following cardiopulmonary death using
      extracorporeal membrane oxygenation support.
AB  - Extracorporeal membrane oxygenation (ECMO) has the ability to provide normal
      organ perfusion and oxygenation in the absence of cardiac function and thus has
      the potential to improve viability of subsequently transplanted kidneys. In
      addition, ECMO support allows the donation following cardiopulmonary death (DCD)
      process to occur in a controlled manner that is acceptable to staff unfamiliar
      with DCD. In 1999 our center implemented a controlled DCD program that
      incorporates post-mortem ECMO support of the organs. Arterial and venous cannulae
      are placed following consent to donate, but prior to withdrawal of support. ECMO
      circulation is initiated immediately following declaration of death. Following a
      brief period where the donor family is allowed to grieve, the donor is moved to
      the operating room where organ recovery occurs. We reviewed the results of 20
      kidney transplants from 13 ECMO supported donors that occurred between October
      2000 and August 2003. One renal allograft was lost due to surgical complications,
      all 19 remaining grafts functioned. An 11% (2/19) delayed graft function rate was
      observed. Kidneys donated from "controlled" ECMO supported CPD donors are a
      viable source of organs for renal transplantation. This recovery method warrants
      further investigation.

PMID- 15478894
TI  - Transplantation from non heart beating donors in Newcastle upon Tyne.
AB  - Donor shortage has led transplant surgeons to reevaluate the concept of non heart
      beating donation. Organs from such donors are exposed to anoxia prior to
      harvesting and a portion of them will consequently present with delayed graft
      function. There is a need for dependable viability testing of organs from less
      than ideal NHBD donors and machine perfusion of kidneys provides such a tool. Our
      experience with own design machine perfusion device, studied parameters,
      perfusion solutions and outcomes is presented. Emphasis is placed on the
      incomparability of results obtained from different perfusion systems and the need
      to establish local criteria of kidney viability.

PMID- 15478895
TI  - The use of marginal-suboptimal donor organs: a practical solution for organ
      shortage.
AB  - The demand for organ transplantation has been rapidly increasing as a result of
      rising incidence of end-stage organ failure while the supply of cadaver organs
      from "ideal" or optimal donors has remained low and inadequate to meet the
      increasing demand. Yet many so called "marginal" or "suboptimal" organs have been
      discarded by many centers when many patients die each day while on the waiting
      list. In this review important data from our experience and that of several other
      centers have confirmed that using such marginal organs can provide a viable
      solution to organ shortage. Such organs include those from donors > 55 years,
      children < 5 years, diabetics, non-heart beating cadavers, and organs with
      extended preservation. Such organs can be successfully used with appropriate
      surgical techniques and immunosuppression protocols and the supply of donor
      organs can be increased by 25% to 30%.

PMID- 15478896
TI  - Donation after cardiac death: the University of Wisconsin experience.
AB  - OBJECTIVES: The objective of this analysis was to compare the results of
      transplantation of livers, pancreases, kidneys, and lungs from donation after
      cardiac death (DCD) donors to organs transplanted from donation after brain death
      (DBD) donors. METHODS: From January 1984 through July 2000, outcomes of 382 DCD
      kidneys were compared to 1,089 kidneys (SPK) transplants and 36 liver transplants
      from DCD donors were compared to 455 SPK and 510 liver transplants from DBD
      donors. Likewise, 31 simultaneous pancreas-kidneys transplants from DBD donors.
      RESULTS: The rate of delayed graft function (DGF) was higher in kidneys
      transplanted from DCD donors (27.5% versus 21.3%, p=0.01). Likewise, discharge
      creatinines were higher in recipients of DCD kidneys (1.9 mg/dL versus 1.7 mg/dL,
      p=0.001). There was no difference in 10-year graft survival between DCD and DBD
      recipients (45.0% versus 48.0%, p=0.054). No difference in 5-year pancreatic and
      renal allograft survival was seen after SPK from DCD or DBD donors. After liver
      transplantation, biliary strictures were higher in recipients of DCD livers
      (13.9% versus 8.0%, p=0.03). Likewise, 3-year patient and graft survivals were
      lower for recipients of DCD livers (65.8% versus 84.9%, p=0.01; and 58.6% versus
      76.9%, p=0.006). CONCLUSIONS: This large experience with transplantation from DCD
      donors demonstrates that similar patient and graft survivals can be expected when
      compared to recipients of organs from DBD donors.

PMID- 15478897
TI  - Modifications of immune regulations with increasing donor & recipient age.
AB  - Increasing amounts of older recipients are listed for transplantation. Several
      clinical trials have therefore been initiated recently using age-adapted
      immunosuppressive regimens. Preliminary data in an "old-for-old" kidney
      transplant program at our center suggest that the approach favouring reduced
      immunosuppression in aged subjects might not be the best choice. We performed an
      experimental study to investigate the effects of donor and recipient age on renal
      allograft outcome and age associated alterations of the immune response.
      Modifications of the immune response in older recipients were associated with
      increased amounts of memory and alloreactive T-cells and an altered cytokine
      response. Recipient age dependent immune responses contributed to an acceleration
      of chronic graft deterioration, so that recipient age may need to be considered
      as a separate and independent risk factor. Although our experimental data need to
      be confirmed clinically, they suggest a modified and age-adapted
      immunosuppression in elderly recipients during the early posttransplant period.

PMID- 15478898
TI  - Cadaveric & living organ donation. Asian experience.
AB  - The number of organ transplants performed in Asian countries during 2001 and 2002
      are reported along with the present status of dialysis patients. Questionnaires
      were sent to key persons of each country where transplantation currently takes
      place. The total number of organ transplants is gradually decreasing,
      particularly those using cadaveric donors, while liver and lung transplantation
      using living donors are growing in Japan and Korea. Education and stimulation of
      the public is strongly requested to promote donation.

PMID- 15478899
TI  - Brain death associated ischemia/reperfusion injury.
AB  - I/R is an important non-immunological, antigen independent factor influencing
      graft outcome. In addition to its non-specific effects it potentiates graft
      immunogenicity and increases host alloresponsiveness. Originally considered an
      event surrounding organ procurement, preservation and revascularization, it has
      recently been associated with donor conditions such as brain death and the non
      heart-beating donor. Occurring early in the transplant process, it initiates a
      cascade of molecular and cellular events including the release of proinflammatory
      mediators and attraction of various cell types infiltrating the tissues. As a
      consequence, acute and chronic changes develop which influence structure and
      function of the organ which may contribute to reduced graft survival. Eventually,
      attentuation of I/R by strategies interfering with the different processes
      promoted by this insult may constitute a means to improve both short and long
      term graft outcome.

PMID- 15478900
TI  - Reactive oxygen species and molecular biology of ischemia/reperfusion.
AB  - Ischemic reperfusion injury is a complex pathophysiological event associated with
      significant impairment of multiple vascular and cellular responses. Oxidative
      damage due to the presence of radical oxygen species is the essential step that
      initiates a wide range of intracellular stress signaling processes that culminate
      in excessive cytokine and chemokine response, adhesion molecule upregulation and
      nitric oxide overproduction. As we studied all the various mechanisms of injury,
      we began deciphering the best means to treat the ischemic insult by modulating
      those proteins or active mediators that are responsible for the lesion. In this
      manner, we have utilized free radical scavengers, calcium channel blockers,
      membrane stabilizers, vasodilators, exogenous nitric oxide and arginine, adhesion
      molecule blockers and small molecule selectin antagonists, in an effort to
      improve cell function and survival after ischemia and reperfusion. The continuous
      investigation of new and old compounds that mitigate the ischemic injury will
      permit us to advance this important field of medicine.

PMID- 15478901
TI  - Heme oxygenase system in ischemia and reperfusion injury.
AB  - Ischemia/reperfusion injury (IRI) is a multifactorial antigen-independent process
      that affects both early and late graft function after transplantation. The
      complex mechanism of IRI can be attributed to neutrophil accumulation at the site
      of tissue injury, release of pro-inflammatory mediators such as oxygen free
      radicals (OFRs), and cytokines, which lead to cellular injury that culminates in
      the ultimate graft failure. The heme oxygenase-1 (HO-1) system is among the most
      critical of cytoprotective mechanisms activated during the cellular stress. The
      cytoprotection often seen in the transplanted organ following local HO-1
      overexpression may include several factors, such as: a) antioxidant function, b)
      maintenance of microcirculation, c) anti-apoptotic function, and d) anti
      inflammatory function. The role of enhanced endogenous HO-1 overexpression, and
      HO-1 downstream mediators (bilirubin, ferritin, CO), which protect against the
      IRI sequel, remain currently one of the most active areas of investigation.
      Indeed, HO-1, which functions to amplify multiple intracellular cytoprotective
      pathways, may serve as a novel therapeutic concept in transplantation to maximize
      organ donor pool through their safer use despite prolonged periods of cold
      ischemia.

PMID- 15478902
TI  - Cell and tissue preservation and storage for transplantation. Present and future.
AB  - Historical remarks and data concerning the present status of tissue preservation
      and storage are presented. Even though, the need for preserved tissue allografts
      is still very high and tissue bank services are very popular, the opinion is
      expressed that the future of tissue banking may be correlated with organ and
      tissue engineering.

PMID- 15478903
TI  - Dendritic cells as regulators of immune reactivity: implications for skin
      transplantation.
AB  - Skin allografts, in contrast to other organ transplants, are acutely rejected
      despite intensive and toxic for the graft recipient immunosuppressive therapy.
      Long-term immunosuppression increases the risk for life-threatening infections
      and cancers. This is why clinical skin allografting practically does not exist.
      Skin Langerhans' (dendritic) cells play a crucial role in the process of
      alloantigen recognition, its processing and initiation of the rejection reaction.
      These cells mature and migrate from the epidermis toward the dermal initial
      lymphatic vessels and further with afferent lymph, as veiled cells, they flow to
      the regional lymph nodes. Since a major goal in transplantation research is to
      understand and exploit the immunogenic properties of "passenger cells" as well as
      the tolerogenic properties of immature dendritic cells, studies concerning
      migrating less matured veiled cells obtained from afferent lymph draining skin
      seem to be relevant. Knowledge of mechanisms responsible for immunological
      synapse formation by veiled cells upon stimulation with allogeneic and bacterial
      antigens and of immunosuppressive drugs effect on this process, as well as of
      localization of Langerhans' cells in skin epidermis and dermis in the
      inflammatory foci, would facilitate a rational approach for the therapeutic
      protocols enabling the prolongation of skin allograft survival time.

PMID- 15478904
TI  - Social and cultural issues in organ transplantation in Islamic countries.
AB  - The importance of religion In Islamic countries is undoubted. Fatwas (opinion
      from religious scholars) have been passed in most Islamic countries approving the
      concepts of brain death and organ transplantation. There are some specific points
      that have be considered while talking of organ transplantation in Islamic
      countries. They include public attitude, taking organ(s) from donors who have
      committed suicide, the influence of local Imams as well as feeding breast milk,
      concept of spousal donation, timing of death as well as soul departure and
      extended families that exist in these countries. Sound knowledge of these factors
      is mandatory to any transplant coordinator and lack of sensitivity to these
      issues could be disastrous.

PMID- 15478905
TI  - Strategies for evaluation of suitable donors: Italian experience.
AB  - Italy was lacking standardised procedures for donor safety evaluation. We
      developed practice guidelines, while a panel of experts coordinated by the
      National Transplant Centre, is available 24 hours a day to support decisions in
      difficult cases. The guidelines identify five levels of risk and give
      recommendations for the utilization of donors with HBV and HCV infections as well
      as for malignancies with negligible or very low risk of transmission. In
      conclusion we aim to standardize the process of donor evaluation across Italy, to
      increase the pool of utilised donors and to reduce the risk of communicable
      disease transmission.

PMID- 15478906
TI  - Donor characteristics can influence overall transplant activities: the Italian
      experience.
AB  - The notable increase in organ donations and transplants in Italy in recent years
      has lead to the development of an atypical approach to kidney transplantation.
      All propitious considerations left aside regarding the organ donation rate which
      has placed Italy among the European leaders, a careful comparative evaluation of
      the data taken from Italian and international registries demonstrates that renal
      transplantations in Italy have not shared the same significant growth. The
      typology of the donors has influenced in a decisive way not only the number of
      renal transplantations, but also the access to transplant for some age groups and
      probably even the quality and cost. The overall view which emerges is complex and
      somewhat contradictory, but we believe that this perspective can furnish solid
      arguments for choices that need not to be delayed for the living donor
      transplant, the divulgence of a donation culture in the population, and the
      criteria for the allocation of the organs.

PMID- 15478907
TI  - Non heart beating donors. Succesfully expanding the donor's pool.
AB  - OBJECTIVES: Expand the donors pool is one of the most hastening problems among
      transplant coordination teams all over the world. Our Hospital outlined thirteen
      years ago a specific policy to increase donors pool with non-heart-beating-donors
      program. METHODS: We have developed an specific program, called "code 9" to get
      donors from "previously healthy" people who die of sudden or unexpected death.
      Madrid has one of the best emergency medical services all over the world, with
      response time under eight minutes, and being able to perform all kind of advanced
      life support maneuvers in situ and during transfer to hospital. RESULTS: From
      1989 we have reported the goodness of the program and the excellence of the
      organs transplanted. In Madrid, one of the most active communities in Spain in
      organ donors procurement, 33% of donors comes from this program. Organs and
      tissues obtained are of same or better quality than those obtained from
      encephalic death donors. CONCLUSIONS: Non-heart beating programs are a good
      option to increase donors pool.

PMID- 15478908
TI  - Early graft function in kidney transplantation from non-heart-beating donors.
AB  - The shortage of kidneys for transplantation is a universal problem. The non heart
      beating donor (NHBD) is one such source. This study evaluates the early graft
      function after kidney transplantation from NHBD. We report our experience with
      126 kidney transplantations retrospectively. As a result, the kidney from NHBD
      over 50 years of age, led to the longer ATN and high PNF (13.8+/-12.6 days and
      16.9% respectively). TIT more than 720 min or less had statistically correlated
      with the length of ANT (13.3 v. 8.4 days). Significant higher incidence of PNF
      (19.3%) was shown in the group of TIT more than 720 min with WIT of 20.8+/-31.6
      min. Significant low flow by machine perfusion was resulted in PNF. In
      conclusion, we suggest that early and delayed graft function of kidneys from NHBD
      should be recognized as a separate clinical entity with its own significant
      effects.

PMID- 15478909
TI  - Renal transplants using expanded cadaver donor criteria.
AB  - AIMS: to analyze the frequency of transplants using expanded donor criteria (EDC)
      and the incidence of delayed graft function, acute rejection and the patient and
      graft survival compared to ideal donors (ID). PATIENTS: retrospective analysis of
      the 582 cadaver renal transplants performed from Jun 1988 to Mar 2003 in adult
      recipients. The expanded donor criteria were considered as history of
      hypertension or evidence of atherosclerosis, diabetes, age less than 5 or more
      than 55 years old, serum creatinine higher than 2.0 mg/dL, shock and retrieval in
      cardiac arrest. The statistical analysis used was Student t test, Chi-square
      test, and Kaplan-Meier method as indicated. RESULTS: 25.4% of our transplants
      used expanded criteria donor. Comparing, respectively, the EDC and ID we found:
      the incidence of delayed graft function of 63.9% vs 50.4% (P: 0.007); incidence
      of acute rejection of 66.1% vs 72.3% (P: 0.203). The patient survival at 1 and 5
      years was 87% vs 92% and 81% vs 79%, respectively (P: 0.6809). The graft survival
      at 1 and 5 year was 74% vs 82% and 57% vs 59% (P: 0.2072), respectively for EDC
      and ID. CONCLUSIONS: One fourth of our cadaver transplants fulfilled the extended
      donor criteria. The incidence of delayed graft function was higher in these
      transplants, but the prevalence of rejection episodes was similar to ideal
      donors. The patient and graft survival were not statistically different at 1 and
      5 year.

PMID- 15478910
TI  - Excellent outcome of renal transplantation using single old kidneys in old
      recipients.
AB  - Aim of this monocentric study is to compare the outcome of 101 renal transplants
      performed in patients older than 55 years with single kidney retrieved from
      donors older than 50 years, with 263 transplants performed in patients younger
      than 55 years transplanted with young kidneys. Delayed graft function (DGF) had
      similar incidence (24 vs 23%). Acute rejections (AR) were fewer in younger
      recipients without statistical significance. A 6-month serum creatinine < 130
      mmol/L was less frequent in older recipients (RR 1.20; p=0.004). 5-year patient
      survival rate was lower in older patients (80.6% vs 92.6%; p=0.009). Crude 5-year
      graft survival rate was lower in older recipients (68.5% vs 84.5%; p=0.004).
      Adjusting for death with functioning kidney 5-year graft survival was still, but
      not significantly, lower in older recipients (82.8% vs 90%; p=NS). This data
      outline that graft survival rate must be always adjusted for death with
      functioning grafts and that excellent outcomes with a 5-year graft survival,
      higher that 80% can be obtained in old patients using single cadaveric kidneys.

PMID- 15478911
TI  - Younger dialytic patients are really at risk to be not transplanted. The Tuscany
      experience.
AB  - The huge increase in organ donation (27.2 pmp in 2002), that characterized our
      regional transplant program was mainly due to the increase of marginal (older)
      donors. As allocating organs coupling donor and recipient age is mandatory, aim
      of this study was to verify the consequences of such retrieval policy over the
      renal transplant activity. According our longitudinal data younger uremic
      patients in Tuscany waiting list for transplantation, have the lowest chance to
      receive kidney transplantation, mainly with respect to older patients that are
      easily removed from the waiting list. This unfair condition need to be corrected
      either by promoting living donation, either increasing cadaveric donation from
      younger donors.

PMID- 15478912
TI  - Prospective randomised trial of the use of Daclizumab in renal transplantation
      using kidneys from non heart beating donors.
AB  - OBJECTIVES: Transplantation using non-heart beating donors (NHBD) is one way of
      reducing the global kidney shortage. Unfortunately the large warm ischaemic
      insult sustained by the graft leads to a high rate of delayed graft function
      (DGF). We have investigated the use of a regimen utilising an II-2r blocker (DZB)
      in place of Tacrolimus for the initial post-operative immunosupression with the
      aim of reducing the incidence of DGF. METHODS: Prospective randomised controlled
      trial based in two NHBD UK centres (Leicester and Newcastle). 51 patients were
      enrolled over two years and randomised into two treatment arms: 1.
      DZB/MMF/Steroids (Tacrolimus started when creatinine dropped below 350
      micromol/l) 2. Tacro/MMF/Steroids. RESULTS: There was one death, during the study
      period, in a patient who had had a non-functioning graft removed. The overall
      incidence of immediate function (IF) was higher than expected (28%), no
      significant difference was found in the incidence of immediate graft function
      between the two groups (35% group 1 and 22% group 2). Sub-group analysis however
      has shown a significant advantage for the delayed introduction of Tacrolimus for
      machine perfused grafts (IF: 53% vs 13%, chi2 p=0.015). There was no difference
      in the rate of rejection. CONCLUSIONS: The delayed introduction of Tacrolimus
      reduces the incidence of DGF in machine-perfused NHBD kidney transplantation.

PMID- 15478913
TI  - Weight increase during machine perfusion may be an indicator of organ and in
      particular, vascular damage.
AB  - OBJECTIVES: Hypothermic machine perfusion preservation has been shown to improve
      the outcome of renal grafts from non-heartbeating donors. We have noticed that
      organs gain a variable amount of weight during perfusion. METHODS: All grafts,
      whether used or discarded, were assessed with respect to their weight gain.
      Primary outcome measures were the results of viability testing. Secondary
      outcomes were early transplant variables including incidence and duration of
      delayed graft function and histological examination of protocol graft biopsies.
      RESULTS: Weight increase data was available on 97 grafts. There were no
      significant differences in weight gain between kidneys used and discarded (17% vs
      20%). 14 patients received grafts which gained over 30% of their initial
      retrieval weight. There were no significant differences in secondary outcome
      measures between this group of recipients and patients who had received less
      "waterlogged" kidneys. Histological changes including endothelial inflammation
      and oedema were observed. CONCLUSIONS: Kidney grafts which have gained over 30%
      of weight on hypothermic machine perfusion preservation can be transplanted
      successfully. Complex interactions between the period of warm ischaemia, in situ
      flushing, perfusion pressures and perfusate probably lead to the phenomenon of
      excessive graft weight gain.

PMID- 15478914
TI  - Reperfusion injury in renal transplantation: comparison of LD, HBD and NHBD renal
      transplants.
AB  - Comparison of reperfusion injury in kidneys transplanted from LD, HBD or NHBD
      donors is presented in the paper. Central venous blood samples (taken during
      perioperative period) was assessed for free radicals, total antioxidant activity
      and various markers of tissue injury. There was demonstrable ischemia reperfusion
      injury occurring at the time of revascularization, which was particularly notable
      in kidneys transplanted from NHBD donors.

PMID- 15478915
TI  - Preservation of rat livers by cold storage: a comparison between the University
      of Wisconsin solution and Hypothermosol.
AB  - OBJECTIVES: The University of Wisconsin solution (UW) is the gold standard for
      cold storage (CS) of donor livers. However, UW contains the colloid Hydroxyethyl
      starch (HES), which may cause perfusion deficits due to its high viscosity.
      Recently, a new CS preservation solution, Hypothermosol (HTS), was introduced
      which contains the less viscous colloid Dextran. The aim of this study was to
      assess HTS as a cold storage solution for preservation of the liver. METHODS: In
      an isolated perfused rat liver model, hepatocellular damage was assessed after 24
      hours of CS. Liver enzymes were measured during reperfusion with Krebs-Henseleit
      Buffer. Bile was collected during reperfusion as a parameter of liver function.
      RESULTS: CS using HTS showed a significant decrease of ALT and LDH levels (as
      compared to UW) at all time points during reperfusion. For LDH these results
      where most pronounced at t=10 min (84 +/- 7.09 vs 113 +/- 7.57: p < 0.05) and
      t=30 min (149.2 +/- 9.68 vs 194 +/-6.52: p< 0.05). Regarding liver function, more
      bile was produced after 24 hours CS in HTS, but this did not reach statistical
      significancy. CONCLUSIONS: Cold storage preservation of rat livers using
      Hypothermosol results in equal or even better preservation as compared to cold
      storage using UW.

PMID- 15478916
TI  - The first disposable perfusion preservation system for kidney and liver grafts.
AB  - Machine perfusion systems for continuous hypothermic perfusion preservation are
      computer controlled and re-usable. The system of perfusion preservation proved
      beneficial for for storage of kidneys, particularly those harvested from NHBD
      donors. The first disposable continuous hypothermic perfusion system which can be
      used for storage of livers is presented.

PMID- 15478917
TI  - DNA released from ischemic and rejecting organs as an indicator of graft cellular
      damage.
AB  - Donor cellular debris contains fragments of nuclei with genetic material. The
      question arises whether the amount of donor graft released DNA accumulating in
      the recipient lymphoid tissues after transplantation could be a measure of donor
      organ damage caused by ischemia and preservation as well as rejection. We found
      that donor heart passenger cells do not contribute to the DNA disseminated in the
      recipient. All donor DNA was, then, derived from the damaged graft cells.
      Immediately and 1 day after transplantation, it was present in blood (plasma and
      cells) to accumulate later in the spleen. Higher values of donor DNA in the
      syngeneic than allogeneic combination, most evident on day 7, were presumably due
      to better perfusion of graft not undergoing rejection. Immunosuppression
      attenuated donor DNA release and accumulation in recipient tissues, nevertheless,
      relatively high concentrations could still be detected. Further studies are in
      progress on the usefulness of measuring DNA concentration for evaluation of the
      graft damage.

PMID- 15478918
TI  - Ethical considerations on kidney transplantation from living donors.
AB  - Our study population consisted of 402 Living Related Donors (LRD)--of which 344
      pairs shared 1 haplotype (Group A) and of 209 Living Unrelated Donors (LURD)
      (Group B): 175 between spouse pairs (Group C)--132 from wife to husband (Group
      C1) and 43 from husband to wife (Group C2) as well as 32 between relatives in law
      or emotionally related patients and 2 between members of clergy (Group D). 199
      pairs showed 3-6 HLA A B Dr mismatches (MM) with the donor and in 10 cases 0-2
      MM. Donor and recipient mean age was 49 +/- 13.4 and 29 +/- 10.3 in Group A and
      respectively 46 +/- 11.2 and 48 +/- 9.6 in Group B. The post-transplant
      immunosuppression therapy was based on Cyclosporin A (CsA). Chi2 test was used to
      assess statistical significance. Donor mortality was 0%; perioperative morbidity
      was 15.2%. Graft function immediately started after surgery. The actuarial 1 yr,
      5 yrs, 10 yrs and 15 yrs graft survival was in Group A: 94%, 86%, 84%, 75% vs.
      Group B: 89%, 78%, 71%, 70% (NS), Group C1: 90%, 75%, 67%, 69% vs. Group C2: 81%,
      74%, 72%, 62% (NS) and Group C: 88%, 78%, 66%, 60% vs. Group D: 91%, 80%, 71%,
      61% (NS). There was no statistically significant difference between LURD and LRD
      as far as graft survival. In conclusion, we certainly agree with the guidelines
      issued by the International Congress on Ethics in Organ Transplantation (Munich,
      December 10-13,2002): kidney transplantation from living donors is a safe and
      effective procedure and should not be discouraged.

PMID- 15478919
TI  - Living emotionally related renal transplantation (LERT)--single center experience
      in the Balkans.
AB  - BACKGROUND: As elsewhere, the growing organ shortage is a main problem for organ
      transplantation. To solve the problem, we started accepting genetically
      unrelated, but emotionally related living donors. METHODS: In the period of 1998
      2002, 14 LERT are performed in the University Clinical Centre in Skopje, Republic
      of Macedonia. As suitable donors are used predominantly spouses, but also mother
      and brother in law. The immunosuppression included a quadruple protocol with
      Interleukin-2R antagonists, late cyclosporin A, MMF and steroids. The two-year
      graft and patients survival of LERT was compared with 22 living genetically
      related donor transplantation (LRT) performed in the same time. RESULTS: The two
      years graft survival was 100% in LERT and 92% in LRT. There are not any
      significant difference among the medical and surgical complications between the
      two groups of pts. The actual serum creatinin was 101+22 in LERT compared with
      142+34 in LRT. CONCLUSION: The authors recommend the LERT as a valid alternative
      especially in the countries where the regular cadaver transplantation is not yet
      established.

PMID- 15478920
TI  - Copper adsorption with Pb and Cd in sand-bentonite liners under various pHs. Part
      II. Effect on adsorption sites.
AB  - The project examined the effect of Pb and Cd on Cu adsorption using sand liners
      containing 0, 5, and 10% sodium bentonite and exposed to metal solutions at three
      pH levels (3.7, 5.5, and 7.5). Aliquots of 2 g of liner material were exposed in
      duplicate, for 14 days, to solutions containing Cu alone or Cu with either Pb or
      Cd. Selective sequential extraction (SSE) was used to quantity the Cu adsorbed by
      each liner particle adsorption site (exchangeable, carbonate and hydroxide,
      oxides and residual). The results indicated that two main factors affected liner
      material behavior in adsorbing Cu, besides Cd and Pb competition: pH either above
      or below 6.5; liner cation exchange capacity (CEC) greater or equal and greater
      than the solution cation equivalence. In general, the liner carbonate and
      hydroxide fractions precipitated the greatest amount of Cu, under all
      environmental conditions while the exchangeable, oxide and residual adsorbed more
      or less the same amount. Lead, and to a lesser extent Cd, significantly increase
      the mobility of Cu, by competing especially for the exchangeable sites. While Cd
      also competed against Cu for oxide adsorption, Pb competes for calcium and
      hydroxide precipitation. Lead, and to a lesser extent Cd, competed especially for
      the exchangeable site where the adsorption is more dynamic, and less for the more
      permanent adsorption sites, involving precipitation, and electrostatic bonding.

PMID- 15478921
TI  - Copper adsorption with Pb and Cd in sand-bentonite liners under various pHs. Part
      I. Effect on total adsorption.
AB  - Municipal solid wastes could be segregated based on their specific heavy metal
      content and disposing of them in separate landfill cells. Therefore, the
      objective of the project was to investigate the interaction between copper (Cu)
      and either lead (Pb) or cadmium (Cd) using equilibrium batch adsorption
      experiments. A first test consisted of soaking three types of sand-bentonite
      liner samples (0, 5, and 10% bentonite) with a respective cation exchange
      capacities (CEC) of 2, 6.4, and 10.8 cmol(+)/kg in one of nine solutions
      consisting of a combination of three pH levels (3.7, 5.5, and 7.5) and three
      heavy metal solutions (Cu alone, Cu with Cd, Cu with Pb) each offering a
      respective heavy metal equivalence of 1, 2, and 2cmol(+)/kg of liner. A second
      test set consisted in soaking 5% bentonite liner samples in three solutions at a
      pH of 3.7, with either Cu alone or with Pb or Cd, at 4.8 cmol(+)/kg of liner. For
      up to 14 days, duplicate samples were sacrificed to determine the supernatant Cu
      level and pH. The results indicated that under acidic conditions (pH< 6.5), the
      liner bentonite content, the solution pH and the presence of Pb or Cd
      significantly influenced Cu adsorption. Lead, and to a lesser extent Cd, competed
      with Cu for adsorption sites. Under alkaline conditions (pH> 6.5), carbonate and
      hydroxyl precipitation governed and masked the Pb and Cd competition. Thus, at
      low pH, limiting the presence of Pb in landfill leachate can improve Cu
      adsorption.

PMID- 15478922
TI  - Adsorption of divalent lead ions by zeolites and activated carbon: effects of pH,
      temperature, and ionic strength.
AB  - Lead alloy bullets used at the 2600 military small arm ranges and 9000
      nonmilitary outdoor shooting ranges in the United States are a source of
      mobilized lead ions under conditions of low pH, significant changes in ionic
      strength, changes in the reduction oxidation potential (redox), and through
      binding metal ions to soil organic matter. Once mobile, these lead ions can
      contaminate adjacent soil and water. Batch adsorption kinetic and isotherm
      studies were conducted to compare and evaluate different types of adsorbents for
      lead ion removal from aqueous media. The effects on lead ion absorption from pH
      changes, competing ions, and temperature increases were also investigated.
      Adsorbent materials such as activated carbon and naturally occurring zeolites
      (clinoptilolite and chabazite) were selected because of their relative low cost
      and because the zeolites are potential point-of-use materials for mitigating
      wastewater runoff. Molecular sieves, Faujasite (13X) and Linde type A (5A) were
      selected because they provide a basis for comparison with previous studies and
      represent well-characterized materials. The relative rate for lead ion adsorption
      was: 13X > chabazite > clinoptilolite > 5A > activated carbon. Modeling lead ion
      adsorption by these adsorbents using the Langmuir and Freundlich isotherm
      expressions determined the adsorbents' capacity for lead ion removal from aqueous
      media. 13X, 5A, and activated carbon best fit the Langmuir isotherm expression;
      chabazite and clinoptilolite best fit the Freundlich isotherm. Applications of
      chabazite would require pH values between 4 and 11, clinoptilolite between 3 and
      11, while activated carbon would operate at a pH above 7. Ionic competition
      reduced lead ion removal by the zeolites, but enhanced activated carbon
      performance. Increasing temperature improved adsorption performance for the
      zeolites; activated carbon lead ion adsorption was temperature independent.

PMID- 15478923
TI  - Washing of soil contaminated with PAHs and heavy petroleum fractions using two
      nonionic [correction] and one ionic surfactant: effect of salt addition.
AB  - The aim of this work was to select the surfactant for washing an aged soil
      contaminated with PAHs and heavy hydrocarbons fraction, between two anionic and
      one ionic surfactant. The effect of the addition of salt when washing with the
      ionic surfactant was evaluated. Results of this work indicated the following.
      Soil contaminants concentration as g TPH kg soil(-1) was 17,200 mg kg(-1). All
      washing performances were dependent on the type of surfactant and applied doses.
      In general, best removal efficiencies were obtained with TW80 (59.57%), followed
      very near by E600 (57.67%), and at the en by SDS (39.0%), in comparison to the
      blank assessment (only water), where removal efficiency was about 12%. These
      removal efficiencies were correlated to the MW, CMC, and HLB values of every
      surfactant. SDS efficiencies were quite enhanced by the addition of 1% (60.36%
      removal efficiency) and 2% (70.28% removal efficiency) of NaCl. Its seems that
      there exist two reasons for this phenomena i.e., the diminution in the real value
      of SDS CMC (as reported by many authors) and, the capabilities of NaCl solutions
      to dissolve higher amounts of hydrocarbons than only tap water.

PMID- 15478924
TI  - Monitoring the TiO2-photocatalyzed destruction of aqueous environmental
      contaminants at parts-per-trillion levels using membrane introduction mass
      spectrometry (MIMS).
AB  - Membrane introduction mass spectrometry (MIMS) was used to directly monitor the
      TiO2/UV-photocatalyzed destruction of acetophenone, toluene, and chloroform in
      H2O at ppm to pptr concentrations. The instrument response time was sufficiently
      rapid for these environmental contaminants (1-6min) that "real-time" monitoring
      of their degradation was possible. This method was used to follow the loss of
      toluene at pptr levels and the concomitant formation of one of its primary photo
      oxidation intermediates, methylphenol. These results illustrate the potential use
      of MIMS as a sensitive on-line measurement technique for monitoring
      photocatalytic destruction of trace organic contaminants in water at
      environmentally relevant levels.

PMID- 15478925
TI  - Photooxidative degradation of Acid Red 27 (AR27): modeling of reaction kinetic
      and influence of operational parameters.
AB  - The decolorization and mineralization of Acid Red 27 (AR27), an anionic monoazo
      dye of acid class, were studied by UV/H202 process in laboratory and real
      samples. Effects of different process parameters such as initial H2O2 and AR27
      concentrations, pH and EtOH as an electron scavenger have been studied. H2O2 and
      UV light have a negligible effect when they were used on their own. The
      decolorization rate follows pseudo-first order kinetic with respect to the dye
      concentration. The rate constant of the attack of *OH radicals to the AR27 has
      been estimated through the adoption of a simplified kinetic model (1.03 x 10(8)M(
      1)s(-1)). This model allows predicting the pseudo-first order rate constant and
      concentration of AR27 in different illumination times for different initial
      concentrations of H2O2. Mineralization studies showed, the formation of sulfate
      ions, the decrease of pH and 85% of COD reduction occur in less than 60 min. In
      the real wastewater color removal could be achieved after only 75 min, whereas
      45% of COD reduction occurs after 105 min of illumination.

PMID- 15478926
TI  - The influence of ultra-violet radiation on chicken hatching.
AB  - The influence of UV-B radiation on embryonic development of chickens Hampshire
      breed was investigated. The set eggs with the average weight of 60.0 +/- 0.5 g
      were divided into six groups. The chickens in the control group C were hatched in
      the darkness. The chicken embryos in experimental groups were, during their
      incubation, influenced by UV light: in E1 (1 h a day), in E2 (2h a day), in E3 (3
      h a day), in E4 (4 h a day), and in E5 (5 h a day). After the experiment, we can
      state that UV radiation appealing on chickens embryos of shorter time (1-2 h) was
      reflected in decreasing embryonic mortality in experimental group E1 (1.27 +/-
      0.14%), the embryonic development was accelerated and the weight of hatched
      chickens was increased in group E2 (492.43 +/- 5.02 h and 47.83 +/- 2.62 g,
      respectively). The negative influence of UV radiation was reflected while it is
      longer appealing on chickens embryos (for 3-5 h), mainly by increased embryonic
      mortality in groups E3 (10.27 +/- 1.65%), E4 (58.09 +/- 3.12%), and E5 (100.00 +/
      0.00%). The results obtained are highly significant (p<0.001) in comparison with
      a control group C, as well as, with the experimental groups E1 and E2.

PMID- 15478927
TI  - Development of new toxicity identification evaluation by assessing toxicity
      reduction on adsorption and ion-exchange treatments.
AB  - A new toxicity identification evaluation method for water exhibiting toxicity has
      been suggested by evaluating toxicity reduction resulting from adsorption and ion
      exchange treatments. Adsorption using various adsorbents such as activated
      carbon, chitosan and zeolite, and ion-exchange using cationic and anionic ion
      exchange resins were performed. In addition, toxicity was evaluated by a cell
      survival test using human liver cancer origin cells (HepG2), and the dose
      response data was applied to treatment characteristics. The amount of toxicity
      adsorbed by the various adsorbents was defined based on adsorption isotherm.
      Parameters of the toxicity adsorption isotherm provided information that allowed
      us to identify the toxicity-controlling chemicals in environmental water
      containing various chemicals. The method is promising for water quality
      management because it can be used to identify toxicity-controlling chemicals
      among various environmental pollutants.

PMID- 15478928
TI  - Organic carbon and ammonium nitrogen removal in a laboratory sand percolation
      filter.
AB  - The on-site treatment of wastewaters from single dwellings requires simple, low
      maintenance systems that reduce the chemical and biochemical oxygen demand (COD
      and BOD respectively), ammonium-nitrogen (NH4-N), orthophosphate (PO4-P),
      phosphorus (P), and microorganisms to acceptable concentrations. Sand filters
      have the potential to achieve these reductions. In this study, a sand tank model
      of a percolation trench and filter was constructed in the laboratory, loaded with
      wastewater, and monitored for a period of 293 days. The silty sand filter was
      seeded for 153 days with effluent from an aerobic biofilm treatment unit. The
      filter was then loaded with synthetic wastewater of domestic strength for 193
      days, when the average organic and hydraulic loading rates on the percolation
      trench were 13.33 g BOD/m2 d and 75 L/m2 d respectively. Removal rates of 90% for
      total COD, 99.3% for BOD5, >99% for total NH4-N, 89% for total PO4-P, and 96% for
      total suspended solids (TSS) were recorded during the study. No excessive
      clogging of the sand filter was observed. During the study very good dispersion
      of the wastewater over the sand filter by the percolation trench was recorded.
      The sand filter was simple to construct and operate and achieved excellent
      results.

PMID- 15478929
TI  - Transformation of fulvic substances in the rhizosphere during phytoremediation of
      used motor oil.
AB  - Changes in the chemical composition of fulvic acids in used oil-contaminated
      soils treated with different plant species and fertilization (fertilized, F; and
      nonfertilized, NF) were analyzed by Fourier-Transformed Infrared Spectroscopy
      (FTIR). Soil contaminated with 1.5% (w/w) used motor oil was seeded with
      sunflower (Helianthus annuus)/Indian mustard (Brassica juncea); soybean (Glycine
      max)/green bean (Phaseolus vulgaris); mixed grasses/maize (Zea mays); mixed
      clover (red clover, Trifolium pratense/ladino clover, T. repens); wheat (Triticum
      aestivum)/oats (Avena sativa); and control (no vegetation). FTIR of soil fulvic
      acids under plants at 150 days showed changes in functional groups compared with
      nonvegetated soil fulvic acids. Results indicate the incorporation of oily
      compounds and decomposition of others. Soybean/bean (NF), clover mix (NF), and
      wheat/oats (NF) showed new bands at 1800cm(-1) related to the presence of
      carbonyl groups, associated with microbially induced beta-oxidation of oily
      hydrocarbons. A new band at 2300-2270cm(-1) in sunflower/mustard (F and NF),
      soybean/beans (F and NF) and wheat/oats (NF) indicated the presence of N-based
      degradation products. Fertilizer treatment resulted in new bands at 1400-700 cm(
      1) in soybean/bean and grass/maize. In contrast, clover mix fulvic acid
      experienced disappearance of aromatic bands at 885cm(-1) and in wheat/oats at
      2276cm(-1) (aliphatic-N).

PMID- 15478930
TI  - Decolorization and degradation of xanthene dyes by a white rot fungus, Coriolus
      versicolor.
AB  - The decolorization of six xanthene dyes (conc. 100 microM) by a white rot fungus,
      Coriolus versicolor (C. versicolor), was investigated in liquid culture. The
      decolorization of Fluorescein, 4-Aminofluorescein, and 5-Aminofluorescein by the
      fungus was 85.0, 95.0, and 91.9% after 14 days incubation, respectively. However,
      no decolorization of Rhodamine B, Rhodamine 123 hydrate, and Rhodamine 6G was
      observed. The first three dyes also were decolorized with cell-free extracts from
      C. versicolor. The decolorization activity was 10.2, 6.7, and 7.2 microM min(
      1)mg(-1), respectively. Thin layer chromatography (TLC) analyses indicated that
      degradation of Fluorescein was occurring with the detection of three degradation
      products.

PMID- 15478931
TI  - Landfill leachate treatment by yeast and bacteria based membrane bioreactors.
AB  - Biological treatment of medium-age landfill leachate was investigated on a
      membrane bioreactor. The experiments were conducted in two 5-L reactors with
      immersed hollow fiber microfiltration membranes. One reactor was operated with a
      mixed bacterial culture termed as bacteria based membrane bioreactor (BMBR) while
      the other with mixed yeast culture termed as yeast based membrane bioreactor
      (YMBR). The leachate was characterized with a chemical oxygen demand (COD)
      concentration of 7000-9000mg/L, biochemical oxygen demand (5 days) to chemical
      oxygen demand ratio (BOD5/COD) of 0.35-0.45 and total Kjeldahl nitrogen (TKN) of
      1800-2000mg/L. The performance was assessed with and without ammonia stripping.
      In both the reactors, the average COD and TKN removal efficiency without ammonia
      stripping ranged between 52-66 and 14-28%, respectively. The performance of both
      the membrane bioreactors improved with ammonia stripping in terms of both COD (72
      76%) and TKN (82-89%) removal efficiency. Though, the difference in the
      performance of the BMBR and YMBR was not significant in terms of COD removal, the
      YMBR showed better removal efficiency in terms of BOD5. The molecular weight cut
      off showed that the degradation pathway of the leachate by bacterial and yeast
      are different. In regard to membrane fouling, the YMBR showed better performance
      with lower trans-membrane pressure as well as longer operating time. This
      superior performance of the YMBR could be due to the structure of yeast cells
      which are larger in size as well as reduced soluble extracellular polymeric
      substances (EPS) production, which are the main cause of membrane biofouling.

PMID- 15478932
TI  - Ammonia and pH inhibition in anaerobic treatment of wastewaters, Part I:
      Experimental.
AB  - The influences of pH and ammonia on methane production in the anaerobic treatment
      of an acetic-propionic-butyric acid mixture in batch reactors operated at 37
      degrees C were investigated. Two independent sets of experiments were carried out
      using seeds from two different full-scale industrial anaerobic treatment
      reactors. One of the seeds ("Sludge A") was obtained from an upflow anaerobic
      sludge-blanket (UASB) reactor treating the waste from a potato chips production
      plant. The second sludge seed ("Sludge B") was from an expanded granular sludge
      blanket (EGSB) reactor treating a corn processing waste. Experiments were carried
      out at four different pH values (6.8, 7.4, 7.8, 8.4) and with six different TAN
      (Total Ammonia Nitrogen) values (262mg/L (control), 1000, 1500, 2000, 2500,
      3000). Three vials (triple runs) were used for each pH and TAN value. The sludge
      seeds used in the inhibition tests were not exposed to high levels of ammonia at
      any stage before the tests. For each vial, cumulative methane production was
      monitored for a period long enough for the termination of biogas production.
      Although neither sludge was acclimated to ammonia, the lag-phase times were less
      than 2 days for Sludge A and essentially zero for Sludge B for all TAN and pH
      values. At certain high pH and high TAN values, however, methanogenic activity
      ceased within about 1-3 months; and then activity restarted and methane formation
      rate reached its maximum values after this period. If the experiments had not
      been continued following this period, this reactivation phenomenon would not have
      been detected.

PMID- 15478933
TI  - Ammonia and pH inhibition in anaerobic treatment of wastewaters, Part II: Model
      development.
AB  - A new model to account for the influences of pH and ammonia on methane production
      in the anaerobic treatment of wastewaters is presented. The model is developed
      and evaluated by using two different sets of experimental data obtained using
      seeds from two different full-scale industrial anaerobic reactors. One of the
      seeds was obtained from an expanded granular sludge-blanket (EGSB) reactor
      treating a corn processing waste. The other seed was obtained from an upflow
      anaerobic sludge-blanket reactor (UASB) treating waste from a potato chips
      production plant. Model development is based on the data collected at four
      different pH values (6.8, 7.4, 7.8, 8.4) and with six different TAN (Total
      Ammonia Nitrogen) values (262mg/L (control), 1000, 1500, 2000, 2500, 3000). The
      proposed model has a considerably more convenient form compared to other models
      that have been used in the literature for similar purposes. For example, the
      model facilitates the calculation of quantities such as the optimal pH as a
      function of TAN concentration, or the TAN concentration leading to 50% inhibition
      (TAN50) as a function of pH. High levels of correlations were achieved by the
      application of the proposed model to the experimental data obtained during our
      studies.

PMID- 15478934
TI  - Purification of electroplating wastewaters utilizing waste by-product ferrous
      sulfate and wood fly ash.
AB  - A new procedure for electroplating wastewater treatment using waste by-product
      (ferrous-sulfate) and waste (wood fly ash) is presented. Ferrous-sulfate was
      employed for Cr(VI) reduction whereas neutralization and heavy metal removal from
      electroplating wastewaters was performed using wood fly ash. Heavy metal removal
      efficiency varied from 97.5% for Cu to 99.973% for Zn. Satisfying results can be
      achieved already at the pH 8. The method is suitable for the purposes of
      wastewater treatment and disposal in compliance with environmental laws.
      Furthermore, it is technically simple, cost-efficient and requires less space
      compared to the classical methodology. According to the composition of its water
      extractable fraction remaining waste ash could be safely deposited on domestic
      waste repositories.

PMID- 15478935
TI  - Effects of periods of nonuse and fluctuating ammonia concentration on biofilter
      performance.
AB  - A systematic study on the transient behavior of odor treatment using biofilters
      is described. The biofilters were exposed to variations in contaminant loading
      and periods of nonuse. Two bench-scale biofilters with different filter media
      were used. Mixtures of compost/perlite (5:1) and dry sludge/granular active
      carbon (5:1) were used as filter media. Ammonia (NH3), one of the main malodorous
      gases, was used as the target compound. The response of each biofilter to
      variations in contaminant mass loading, periodic nonuse, water content, and inlet
      concentration pulse was studied. The nonuse period comprised of two stages: the
      "idle phase" when no air was passing through the biofilters, and the "no
      contaminant-loading phase" when only humidified air was passing through the
      biofilters. Concentration spike was applied to study the effects of shock loading
      on the biofilter performance. Biofilters responded effectively to NH3
      concentration variations and shock loading by rapidly recovering to the original
      removal rates within 6-12h. The results indicated re-acclimation times ranged
      from several hours to longer than a day. Longer idle phase produced longer re
      acclimation periods than periods of no contaminant loading. When the media was
      dried during the biofiltration process, elimination capacity dropped accordingly
      for both biofilters. After 24 h of drying, the biofilter experiment could be
      restarted and run for a few days for recovering.

PMID- 15478936
TI  - Effects of crude oil, oil components, and bioremediation on plant growth.
AB  - The phytotoxic effects of crude oil and oil components on the growth of red beans
      (Phaseolus nipponesis OWH1) and corn (Zea mays) was investigated. In addition,
      the beneficial effects of bioremediation with the oil-degrading microorganism,
      Nocardia sp. H17-1, on corn and red bean growth in oil-contaminated soil was also
      determined. It was found that crude oil-contaminated soil (10,000mg/kg) was
      phytotoxic to corn and red beans. In contrast, obvious phytotoxicity was not
      observed in soils contaminated with 0-1000 mg/kg of aliphatic hydrocarbons such
      as decane (C10) and eicosane (C20). Phytotoxicity was observed in soils
      contaminated with 10-1000mg/kg of the poly aromatic hydrocarbons (PAHs)
      naphthalene, phenanthrene, and pyrene. It was observed that phytotoxicity
      increased with the number of aromatic rings, and that corn was more sensitive
      than red beans to PAH-contaminated soil. Bioremediation with Nocardia sp. H17-1
      reduced phytotoxicity more in corn than in red bean, suggesting that this
      microbial species might degrade PAHs to some degree.

PMID- 15478937
TI  - Separation of gallium and arsenic from the wafer grinding extraction solution.
AB  - This work investigates the separation of gallium and arsenic from the wafer
      grinding extraction solution. The wafer grinding extraction solution was
      generated using hot and concentrated nitric acid. In this study, adsorption
      technology was employed to remove the toxic arsenic from the extraction solution.
      Ferric hydroxide was the adsorbent employed to adsorb arsenic. The effects of pH
      value, contact time, absorbent dosage, and chloride ion concentration on the
      efficiency of adsorption of gallium and arsenic were investigated. The optimal
      conditions for recovering gallium and removing arsenic were a raw pH of 0.2, a
      contact time of 6min and a ferric hydroxide concentration of 30.4g/L.
      Additionally, adding chloric ions reduces the residual percentage of gallium
      (ReGa) and the percentage of arsenic removed (RAs). Under these optimal
      conditions, ReGa and RAs are 100 and 80%, respectively.

PMID- 15478938
TI  - A photometric method for ozone determination using alizarin violet.
AB  - A photometric method for on-line determination of ozone is reported based on the
      reaction of alizarin violet with ozone at basic pH 10. The method is applied to
      determine the concentrations of ozone generated using an ozonizer and is compared
      with iodide method as guide lined by the International Ozone Association.
      Alizarin violet reacts with ozone in 6:1 stoichiometric ratio. The method is
      simple, reliable, and reproducible. Ozone concentrations in the range 1.0-5.0mg
      L(-1) can be determined on-line with out change in procedure.

PMID- 15478939
TI  - Environmental contamination assessment of the surroundings of the ex-Sibenik's
      ferro-manganese smelter, Croatia.
AB  - The objective of this study was chemical and radiological characterization of
      soil samples affected by the dust emission and slag dumping from ferro-manganese
      smelter as well as uptake of metals by vegetation growing on that soil. Iron was
      the main component of metallurgical slag deposited near the smelter. Slag
      material was highly enriched in Zn, Cr, Cu, Co, and Pb. V and Cr were enriched in
      the soil taken near the smelter approximately by a factor of two, Pb and Cu were
      increased fivefold whereas the mean content of Mn was about 130 times higher than
      the levels in background soil samples. Activities of agricultural soil samples
      were typical for the soil developed on late Cretaceous carbonate surface. 40K,
      232Th, and 137Cs showed somewhat lower activities in background soil compared to
      the soil taken near the smelter while the opposite was found for 226Ra and 238U.
      Plot of factor 1 against factor 2, obtained by Principal component analysis,
      showed perfect separation of the samples taken in the vicinity of the smelter,
      slag material, and normal background agricultural soil. Perfect correlation
      (Canonical R =0.992) was obtained between chemical composition of soil and
      vegetation samples taken from the same spots. The content of Mn was approximately
      36 times higher in vegetation taken from the vicinity of the smelter compared to
      the background values.

PMID- 15478940
TI  - Effect of environmental exposure to cadmium on pregnancy outcome and fetal
      growth: a study on healthy pregnant women in China.
AB  - The objective of the present study was to evaluate the potential effect of
      environmental exposure to cadmium on pregnancy outcome and fetal growth. Normal
      pregnant women were selected from Da-ye city of Hubei province, a cadmium
      polluted area, from November 2002 through January 2003. Whole blood of pregnant
      women, cord blood, and placenta were collected and cadmium levels were determined
      by inductively coupled plasma emission mass spectroscopy. Incidence rate of
      preterm labor (gestational age < or = 37 weeks) and neonatal asphyxia, neonatal
      birth height, and birth weight were compared between lower and higher cadmium
      exposure level groups. Whole blood cadmium of 44 mothers ranged from 0.80 to
      25.20 microg/L. Cadmium concentration in maternal blood was significantly higher
      than that in cord blood (t = 11.44, P < 0.01). Placenta cadmium ranged from 0.084
      to 3.97 microg/g dry weight. After adjustment for maternal age, history of
      gestation, abortion and lactation, Logistic regression analysis showed that there
      was no significant association between cadmium exposure levels and pregnancy
      outcome (premature labor or neonatal asphyxia). Multiple linear regression
      analysis showed that, cord blood cadmium level, but not maternal blood cadmium
      and placenta cadmium, was significantly negatively associated with neonatal birth
      height (t= -2.33, P < 0.05). Compared with lower cord blood cadmium level (< or =
      0.40 microg/L), higher level of cord blood cadmium (>0.40 microg/L) was
      associated with 2.24cm decrease in neonatal birth height. There was no
      significant association between cadmium exposure and birth weight. It was
      concluded that environmental exposure to cadmium significantly lower neonatal
      birth height.

PMID- 15478941
TI  - Distribution characteristics of rare earth elements in children's scalp hair from
      a rare earths mining area in southern China.
AB  - In order to demonstrate the validity of using scalp hair rare earth elements
      (REEs) content as a biomarker of human REEs exposure, data were collected on REEs
      exposure levels from children aged 11-15 years old and living in an ion
      adsorptive type light REEs (LREEs) mining and surrounding areas in southern
      China. Sixty scalp hair samples were analyzed by ICP-MS for 16 REEs (La Lu, Y and
      Sc). Sixteen REEs contents in the samples from the mining area (e.g., range: La:
      0.14-6.93 microg/g; Nd: 0.09-5.27 microg/g; Gd: 12.2-645.6ng/g; Lu: 0.2-13.3
      ng/g; Y: 0.03-1.27 microg/g; Sc: 0.05-0.30 microg/g) were significantly higher
      than those from the reference area (range: La: 0.04-0.40 microg/g; Nd: 0.04-0.32
      microg/g; Gd: 8.3-64.6 ng/g; Lu: 0.4-3.3ng/g; Y: 0.03-0.29 microg/g; Sc: 0.11
      0.36 microg/g) and even much higher than those published in the literature. The
      distribution pattern of REEs in scalp hair from the mining area was very similar
      to that of REEs in the mine and the atmosphere shrouding that area. In
      conclusion, the scalp hair REEs contents may indicate not only quantitatively but
      also qualitatively (distribution pattern) the absorption of REEs from
      environmental exposure into human body. The children living in this mining area
      should be regarded as a high-risk group with REEs (especially LREEs) exposure,
      and their health status should be examined from a REEs health risk assessment
      perspective.

PMID- 15478942
TI  - Performance of two new electrochemical treatment systems for wastewaters.
AB  - Two types of practical electrochemical treatment systems (treatment capacities of
      4 and 0.5 m3/h) were constructed. These systems generate radical species for
      effective oxidation of organic pollutants in wastewater, providing a novel
      treatment system for treating various kinds of wastewater. A series of
      experiments was performed using effluents from an anaerobic digester (EAD) of
      cattle wastewater, supernatants from primary sedimentation in a sewage plant
      (SPS), and domestic wastewater to evaluate the systems' treatment abilities. As a
      result, for both EAD and SPS, the 4 m3/h system was found to remove 87-91% of T
      P, 74-96% of T-N, 70-94% of NH4-N, 88-91% of TOC, 75-87% of COD. Similarly, for
      wastewater, the 0.5 m3/h system was able to remove 62-90% of T-P, 83-92% of T-N,
      90-100% of NH4-N, 75-83% of TOC, 80-100% of COD. It was further demonstrated that
      the high-voltage pulses and ultrasonic treatment effectively decomposed NH4-N and
      TOC due to the formation of radical species such as hydroxyl radicals and
      hypochlorite, T-P was removed by the electrocoagulation.

PMID- 15478943
TI  - Viramidine demonstrates better safety than ribavirin in monkeys but not rats.
AB  - The safety of viramidine was evaluated and compared with ribavirin in one-month
      and six-month studies in rats and one-month and nine-month studies in monkeys.
      Viramidine administration produced hemolytic anemia, characterized by decreases
      in hemoglobin (Hgb) concentrations, which was accompanied by erythroid
      hyperplasia of the bone marrow or increase in reticulocyte counts. In the 1-month
      study in rats, viramidine or ribavirin dosing at 120 mg/kg/day reduced Hgb
      concentrations (12-16% and 13-20% compared to controls, respectively) and caused
      slight erythroid hyperplasia in the bone marrow. In the 6-month study in rats,
      viramidine or ribavirin dosing at 90 mg/kg/day reduced Hgb concentrations (16-18%
      and 18% compared to controls, respectively) and increased reticulocyte counts
      (>25%). Although toxicity effects in monkeys were similar to rats, they occurred
      at higher doses of viramidine compared to ribavirin. In the 1-month monkey study,
      viramidine at 600 mg/kg/day caused slight or no reduction (9%-0% in males and
      females) in Hgb concentrations compared to moderate reduction for ribavirin at
      300 mg/kg/day (14%-20% in males and females). There were no signs of erythroid
      hyperplasia in bone marrow or significant increase in reticulocytes detected
      after viramidine or ribavirin dosing in monkeys. In the 9-month study in monkeys,
      viramidine at 180 mg/kg/day slightly reduced Hgb concentrations (5-11%) as
      compared to ribavirin at 60 mg/kg/day (9-12%). Both treatments had an increase in
      reticulocytes (49-53% vs. 43-59% compared to controls, respectively). Moderate
      decrease in Hgb levels (26-29%) together with large increase in reticulocyte
      counts (203-224%) were seen for viramidine at 600 mg/kg/day. All the changes were
      reversible after a recovery phase in both rats and monkeys. It is concluded that
      ribavirin and viramidine produced similar toxicity in rats. However, viramidine
      is safer than ribavirin in monkeys.

PMID- 15478944
TI  - Flunarizine: a possible adjuvant medication against soman poisoning?
AB  - Organophosphate (OP) nerve agents are amongst the most toxic chemicals. One of
      them, soman, can induce severe epileptic seizures and brain damage for which
      therapy is incomplete. The present study shows that pretreatment with flunarizine
      (Flu), a voltage-dependent calcium channel blocker, when used alone, does not
      produce any beneficial effect against the convulsions, neuropathology and
      lethality induced by soman. Flu was also tested in combination with atropine
      sulfate and diazepam. In this case, although only some results reach statistical
      significance, an encouraging general trend toward an improvement of the
      anticonvulsant, neuroprotective and antilethal capacities of this classical anti
      OP two-drug regimen is constantly observed. In the light of these findings, it
      seems premature to definitely reject (or recommend) Flu as a possible adjuvant
      medication against soman poisoning. Further studies are required to determine its
      real potential interest.

PMID- 15478945
TI  - Ciprofloxacin-induced glutathione redox status alterations in rat tissues.
AB  - The possible oxidative stress inducing effect of a fluoroquinolone (FQ)
      antibiotic, ciprofloxacin (CPFX), was investigated in rats measuring glutathione
      redox status. For this purpose, the drug was administered to rats as two
      different single doses (100 and 150 mg/kg, ip) or a repeated dose (500 mg/kg/d,
      ig, for 5d). Then, total and oxidized glutathione levels were determined in
      hepatic and cerebral tissues of the rats by an enzymatic cycling assay, and the
      glutathione redox status was calculated. The possible protective effects of
      vitamin E or allopurinol against CPFX-induced alterations on glutathione system
      have also been examined. Following both routes of administration of CPFX, the
      total glutathione content of the liver, but not of brain decreased significantly.
      The oxidized glutathione (GSSG) in the brain increased after single or repeated
      dose treatments, but only with repeated doses of CPFX in the liver. CPFX induced
      dose-dependent alterations in the glutathione redox status in both tissues. With
      single doses the effect was more pronounced in cerebral tissue, and with repeated
      ig doses it was significant in both tissues. Pretreatment of rats with vitamin E
      or allopurinol before the administration of CPFX provided marked protection
      against glutathione redox status alterations in both tissues. Our results, thus,
      indicate that CPFX treatment introduces an oxidative stress in cerebral and
      hepatic tissues of rat.

PMID- 15478946
TI  - Effects of ox-LDL on number and activity of circulating endothelial progenitor
      cells.
AB  - BACKGROUND: Endothelial dysfunction is thought to play a crucial role in the
      pathogenesis of atherosclerosis induced by ox-LDL. Recently, a variety of
      evidence suggested that endothelial progenitor cells (EPCs) participated in
      neovascularization and reendothelialization. However, effects of ox-LDL on EPCs
      number and activity are ill understood. METHODS: Total mononuclear cells (MNCs)
      were isolated from peripheral blood by Ficoll density gradient centrifugation,
      and then the cells were plated on fibronectin-coated culture dishes. After 7 days
      culture, attached cells were stimulated with ox-LDL (to make a series of final
      concentrations: 25 microg/mL, 50 microg/mL, 100 microg/mL, 200 microg/mL), native
      LDL (100 microg/mL) or vehicle control for the respective time points (6 h, 12 h,
      24 h and 48 h). EPCs were characterized as adherent cells double positive for
      DiLDL-uptake and lectin binding by direct fluorescent staining under a laser
      scanning confocal microscope. EPCs were further documented by demonstrating the
      expression of KDR, VEGFR-2 and AC133 with flow cytometry. Proliferation,
      migration and in vitro vasculogenesis activity of EPCs were assayed by MTT assay,
      modified Boyden chamber assay and in vitro vasculogenesis kit, respectively. EPCs
      adhesion assay was performed by replating those on fibronectin-coated dishes, and
      then counting adherent cells. RESULTS: Incubation of isolated human EPCs with ox
      LDL decreased the number of EPCs in concentration-dependent manner, maximum at
      200 microg/mL (approximately 70% reduction, P < 0.001). In time-course
      experiments performed with an ox-LDL concentration of 100 microg/mL, decrease of
      EPCs number became apparent at 12 hours and reached the maximum at 24 hours
      (approximately 50% reduction, P < 0.01). In addition, ox-LDL dose and time
      dependently impaired EPC proliferative, migratory, adhesive and in vitro
      vasculogenesis capacity. CONCLUSION: The results of the present study defined a
      novel mechanism of action of ox-LDL: the reduction of EPCs with decreased
      functional activity.

PMID- 15478947
TI  - Genotoxicity of aspartame.
AB  - In the present study, the genotoxic effects of the low-calorie sweetener
      aspartame (ASP), which is a dipeptide derivative, was investigated using
      chromosome aberration (CA) test, sister chromatid exchange (SCE) test,
      micronucleus test in human lymphocytes and also Ames/Salmonella/ microsome test.
      ASP induced CAs at all concentrations (500, 1000 and 2000 microg/ml) and
      treatment periods (24 and 48 h) dose-dependently, while it did not induce SCEs.
      On the other hand, ASP decreased the replication index (RI) only at the highest
      concentration for 48 h treatment period. However, ASP decreased the mitotic index
      (MI) at all concentrations and treatment periods dose-dependently. In addition,
      ASP induced micronuclei at the highest concentrations only. This induction was
      also dose-dependent for 48 hours treatment period. ASP was not mutagenic for
      Salmonella typhimurium TA98 and TA100 strains in the absence and presence of S9
      mix.

PMID- 15478948
TI  - Effects of BSO and L-cysteine on drug-induced cytotoxicity in primary cell
      cultures: drug-, cell type-, and species-specific difference.
AB  - The effects of DL-buthionine-(S,R)-sulfoximine(BSO) and L-cysteine(CYS) on
      cytotoxicity induced by cisplatin(CP) and diclofenac(DIC) in primary cell
      cultures of hepatocytes and renal tubular epithelial cells(RTEC) isolated from
      rats or monkeys were studied. Hepatocytes and RTEC were inoculated into collagen
      coated 96-well culture plates. After preincubation, a series of concentrations of
      CP or DIC were added, and 16 h and 4 h prior to CP and DIC, 40 microM BSO and 5
      mM CYS were added, respectively. MTT assays were performed to evaluate
      cytotoxicity(concentrations of drug that inhibited 50% cell growth, IC50). CYS
      made IC50s of CP in rat and monkey RTEC increase up to more than 5 mM, but BSO
      made IC50s of CP in rat RTEC lower down with bigger magnitude than that in monkey
      RTEC; similarly, CYS made IC50s of CP in rat hepatocytes increase up to more than
      5 mM, but BSO made IC50s lower down with bigger magnitude than that in rat RTEC.
      However, neither CYS nor BSO had significant effects on all IC50s of DIC in all
      examined cells. These results suggested that during CP-induced stress state, rat
      hepatocytes were more susceptible to changes of GSH level than rat RTEC, and rat
      RTEC were more dependent on intracellular GSH status than monkey RTEC. DIC
      induced cytotoxicity in RTEC and hepatocytes is independent of GSH level.

PMID- 15478949
TI  - Morphological alterations of central nervous system (CNS) myelin in vanadium (V)
      exposed adult rats.
AB  - In the present work we show morphological data of the in vivo susceptibility of
      CNS myelin to sodium metavanadate [V(+5)] in adult rats. The possible role of
      vanadium in behavioral alterations and in brain lipid peroxidation was also
      investigated. Animals were injected intraperitoneally (i.p.) with 3 mg/kg body
      weight (bw) of sodium metavanadate [1.25 V/kg bw/day] for 5 consecutive days.
      Open field and rotarod tests were performed the day after the last dose had been
      administered and then animals were sacrificed by different methods for
      histological and lipid peroxidation studies. The present results show that
      intraperitoneal administration of V(+5) to adult rats resulted in changes in
      locomotor activity, specific myelin stainings and lipid peroxidation in some
      brain areas. They support the notion that CNS myelin could be a preferential
      target of V(+5)-mediated lipid peroxidation in adult rats. The mechanisms
      underlying this action could affect the myelin sheath leading to behavioral
      perturbations.

PMID- 15478950
TI  - Defining spirituality: multiple uses and murky meanings of an incredibly popular
      term.

PMID- 15478951
TI  - A working theology of prison ministry.
AB  - Drawing upon experiences as a prison chaplain and a state director of prison
      chaplaincy services, the author proposes a working theology of prison ministry.
      Such a theology begins with an understanding of the inherent worth of humankind
      as created by God in God's own image, addresses the question of hope, embodies
      the incarnate presence of God by being present with people in their alienation,
      enables the giving and receiving of forgiveness, deals with issues of power and
      control, and respects the diverse paths that humans take in their walk toward and
      with God.

PMID- 15478952
TI  - Pastoral care in a time of global market capitalism.
AB  - The author defines pastoral theology as "the study of the micro-world of
      intrapsychic and interpersonal interactions with the tools of theology and the
      social sciences for the purpose of support and healing. In a typical class or
      supervisory session, we analyze the words, voice inflection, pace, and gestures
      of an intimate conversation between two people, looking for clues to the deep
      structure of personality and intimate relationships. The hope of such study is
      that we will see the revelation of God is love and power in action to validate
      and challenge the theological traditions that give us eyes to see and invite us
      to see more clearly."

PMID- 15478953
TI  - What is spiritual? What is spiritual suffering?
AB  - The author offers definitions for "spiritual" and for "spiritual suffering,"
      suggesting that human spiritual needs include Love, Faith, Hope, Virtue, and
      Beauty. Spiritual suffering is experienced when these needs are unfulfilled.
      Spiritual care involves assisting in the fulfillment of these needs. He considers
      the constant movement between spiritual needs and fulfillments, encouraging use
      of fluid (not static) assessment methods using "spiritual spectra." As a model,
      this outline of basic spiritual needs may serve as the foundation for many
      current spiritual assessment tools.

PMID- 15478954
TI  - Relationship building in Clinical Pastoral Education: a Confucian reflection from
      Asian chaplains.
AB  - The authors reflect on the intentional model of relationship building in Clinical
      Pastoral Education (CPE) and its roots in the Western concept of the self as a
      rational, autonomous, and bounded agent. They compare the Western idea to the
      Confucian two-dimensional self orientation as relational as well as autonomous,
      and discuss possible difficulties that Asian students from Confucian background
      may encounter entering CPE. The chaplains explore implications and suggestions
      for how CPE supervisors and students may enter into dialogue in order to create
      mutual understanding and help Asian students translate CPE learning methods into
      meaningful cultural contexts.

PMID- 15478955
TI  - Chaplain contacts improve treatment outcomes in residential treatment programs
      for delinquent adolescents.
AB  - This is a report of a study of 828 delinquent adolescents who completed
      behavioral treatment during 1995, 1996, 1997 in Holy Cross Children's Services
      programs. The research focused on a measure of chaplain contact time with each
      youth, and three outcome variables: "planned release" (program completion),
      living situation at 12 months after discharge, and a calculated cost of care for
      the 12 month graduates. The findings include statistically significant
      correlations between chaplain time and all three preferred outcome measures. The
      results were significant when age, number of prior incarcerations and religiosity
      variables were controlled for in a regression analysis. When the costs of
      aftercare for the graduates were computed, the average cost-of care-per-day of
      the no-Chaplain-contact graduates was significantly higher than that of the high
      contact group. Based on the findings, the author suggests that chaplain
      involvement in the behavioral treatment of delinquent adolescents improves
      outcomes and is cost effective.

PMID- 15478956
TI  - An analysis of referrals to chaplains in a community hospital in New York over a
      seven year period.
AB  - The study analyzed the pattern of referrals to chaplains in a suburban hospital
      over a 7-year period. Nurses made more than half of all the referrals to
      chaplains, with nursing accounting for 81.74% of referrals from staff members
      other than pastoral care workers and volunteers. Social workers and physicians
      made 11.74% and 4.08% of referrals, respectively. The number of referrals from
      social workers (r=.86, p<.05), nurses (r=.68, p<.10) and other staff (r=.69,
      p<.10) increased across years, with the exception of physicians. Three quarters
      of referrals were requests for chaplains to visit patients and one quarter were
      requests to visit with family or friends. A significant difference was found in
      the percentage of referrals made for patients and family/friends by staff members
      (p<.05), with social workers making a higher percentage of referrals for
      relatives and friends (34.1%), compared to nurses (26.74%) and physicians
      (27.27%). The most common presenting problems for which patients were referred to
      chaplains were anxiety, depression, and pregnancy loss. The rate of referrals for
      patients over the entire study period was 39.04 per 1000 patient stays.

PMID- 15478957
TI  - A parallel process seminar for use in programs of Clinical Pastoral Education
      (CPE).
AB  - A seminar model is developed and used for students in Clinical Pastoral Education
      to explore parallel process dynamics operative in their ministry. One of the key
      assumptions on which this seminar is designed is that students will present
      material from their work with patients that carry relational dynamics that
      parallel the students' intra-psychic dynamics. Verbatim material presented is
      used in the learning group to identify and respond to the presenter's intra
      psychic dynamics and their implication for ministry--to provide support,
      clarification, and/or confrontation with the intent of facilitating personal and
      professional growth.

PMID- 15478959
TI  - The language of presence.

PMID- 15478960
TI  - Structuring chaos.

PMID- 15478962
TI  - Transformation.

PMID- 15478963
TI  - The Knight of Faith: a clinical vignette.

PMID- 15478965
TI  - Effects of piezoelectric coupling on energy trapping of thickness-shear modes.

PMID- 15478964
TI  - The literature on religion and health: caveat emptor.

PMID- 15478966
TI  - AMCXO and its test system.
AB  - In this paper, we introduce a novel temperature compensated crystal oscillator-
      analog memory compensated crystal oscillator (AMCXO), a microcomputer compensated
      crystal oscillator (MCXO) based on an analogue approach, and we compare the
      performance between MCXO and AMCXO, and analyze the necessity of developing
      AMCXO. Both AMCXO and MCXO, combined with their test systems, use computers to
      generate the control signals used for the compensated crystal oscillators
      according to temperature variation. However, the execution devices are much
      different from each other in the practical temperature compensated crystal
      oscillators. A MCXO uses a set of digital units, including a microprocessor, to
      realize the compensation. For it, equations or tables are used to express the
      relationship between the control signal and temperature. An AMCXO uses an
      analogue memory, which has the same functions as the digital units of MCXO. For
      AMCXO, a curve or figure based on the equations or tables is used to express the
      same relationship. Their test systems have obvious distinctions in temperature
      experiment, data acquisition, and processing. A better performance will be
      obtained by using a more complicated AMCXO test system, and the cost can be
      reduced at the same time.

PMID- 15478967
TI  - Spherical Bragg reflector resonators.
AB  - In this paper we introduce the concept of the spherical Bragg reflector (SBR)
      resonator. The resonator is made from multiple layers of spherical dielectric,
      loaded within a spherical cavity. The resonator is designed to concentrate the
      energy within the central region of the resonator and away from the cavity walls
      to minimize conductor losses. A set of simultaneous equations is derived, which
      allows the accurate calculation of the dimensions of the layers as well as the
      frequency. The solution is confirmed using finite-element analysis. A Teflon-free
      space resonator was constructed to prove the concept. The Teflon SBR was designed
      at 13.86 GHz and exhibited a Q-factor of 22,000, which agreed well with the
      design values. This represents a factor of 3.5 enhancement over a resonator
      limited by the loss-tangent of Teflon. Similarly, SBR resonators constructed with
      low-loss materials could achieve Q-factors of the order of 300,000.

PMID- 15478968
TI  - Modeling of wave propagation in layered piezoelectric media by a recursive
      asymptotic method.
AB  - In this paper, a simple asymptotic method to compute wave propagation in a
      multilayered general anisotropic piezoelectric medium is discussed. The method is
      based on explicit second and higher order asymptotic representations of the
      transfer and stiffness matrices for a thin piezoelectric layer. Different orders
      of the asymptotic expansion are obtained using Pade approximation of the transfer
      matrix exponent. The total transfer and stiffness matrices for thick layers or
      multilayers are calculated with high precision by subdividing them into thin
      sublayers and combining recursively the thin layer transfer and stiffness
      matrices. The rate of convergence to the exact solution is the same for both
      transfer and stiffness matrices; however, it is shown that the growth rate of the
      round-off error with the number of recursive operations for the stiffness matrix
      is twice that for the transfer matrix; and the stiffness matrix method has better
      performance for a thick layer. To combine the advantages of both methods, a
      hybrid method which uses the transfer matrix for the thin layer and the stiffness
      matrix for the thick layer is proposed. It is shown that the hybrid method has
      the same stability as the stiffness matrix method and the same round-off error as
      the transfer matrix method. The method converges to the exact transfer/stiffness
      matrices essentially with the precision of the computer round-off error. To apply
      the method to a semispace substrate, the substrate was replaced by an artificial
      perfect matching layer. The computational results for such an equivalent system
      are identical with those for the actual system. In our computational experiments,
      we have found that the advantage of the asymptotic method is its simplicity and
      efficiency.

PMID- 15478969
TI  - Experimental investigation of computed tomography sound velocity reconstruction
      using incomplete data.
AB  - An approach for reconstructing the sound velocity distribution in the breast was
      previously proposed and verified by simulations, and the present study
      investigated the approach experimentally. The experimental setup comprised a 5
      MHz, 128-channel linear array, a programmable digital array system, a phantom
      containing objects with differing physical properties, and a computer. The array
      system was used to collect channel data for simultaneous B-mode image formation
      and limited-angle tomographic sound velocity reconstruction. The phantom was
      constructed from materials mimicking the following tissues in the breast:
      glandular tissue, fat, cysts, high-attenuation tumors, and irregular tumors. The
      sound velocities in these materials matched those in the corresponding real
      tissues. The imaging setup is similar to that of x-ray mammography, in which a
      linear array is placed at the top of the breast and a metal plate is placed at
      the bottom for reflecting sound waves. Thus, both B-mode images and the sound
      velocity distribution can be acquired using the same setup. An algorithm based on
      a convex programming formulation was used to reconstruct the sound velocity
      images. By scanning the phantom at different positions, nine cases were
      evaluated. In each of the nine cases, the image object comprised a background
      (glandular tissue) and one or three regions of interest (fat, tumor, or cyst).
      The sound velocity was accurately estimated in the nine cases evaluated, with
      sound velocity errors being less than 5 m/s in 8 of 11 regions of interest. Thus,
      obtaining the sound velocity distribution is feasible with a B-mode imaging setup
      using linear arrays. Knowledge of the sound velocity distribution in the breast
      can be used to complement B-mode imaging and to enhance the detection of breast
      cancer.

PMID- 15478970
TI  - Direct sampled I/Q beamforming for compact and very low-cost ultrasound imaging.
AB  - A wide variety of beamforming approaches are applied in modern ultrasound
      scanners, ranging from optimal time domain beamforming strategies at one end to
      rudimentary narrowband schemes at the other. Although significant research has
      been devoted to improving image quality, usually at the expense of beamformer
      complexity, we are interested in investigating strategies that sacrifice some
      image quality in exchange for reduced cost and ease in implementation. This paper
      describes the direct sampled in-phase/quadrature (DSIQ) beamformer, which is one
      such low-cost, extremely simple, and compact approach. DSIQ beamforming relies on
      phase rotation of I/Q data to implement focusing. The I/Q data are generated by
      directly sampling the received radio frequency (RF) signal, rather than through
      conventional demodulation. We describe an efficient hardware implementation of
      the beamformer, which results in significant reductions in beamformer size and
      cost. We present the results of simulations and experiments that compare the DSIQ
      beamformer to more conventional approaches, namely, time delay beamforming and
      traditional complex demodulated I/Q beamforming. Results that show the effect of
      an error in the direct sampling process, as well as dependence on signal
      bandwidth and system f number (f#) are also presented. These results indicate
      that the image quality and robustness of the DSIQ beamformer are adequate for low
      end scanners. We also describe implementation of the DSIQ beamformer in an
      inexpensive hand-held ultrasound system being developed in our laboratory.

PMID- 15478971
TI  - Sound speed estimation using automatic ultrasound image registration.
AB  - A mismatch between the sound speed assumed for beamforming and scan conversion
      and the true sound speed in the tissue to be imaged can lead to significant
      defocusing and some geometric distortions in ultrasound images. A method is
      presented for estimating the average sound speed based on detection of these
      distortions using automatic registration of overlapping, electronically steered
      images. An acrylamide gel phantom containing vaporized dodecafluoropentane
      droplets as point targets was constructed to evaluate the technique. Good
      agreement (rms deviation <0.4%) was found between the sound speeds measured in
      the phantom using a reference pulse-echo technique and the image-based sound
      speed estimates. A significant improvement in accuracy (rms deviation <0.1%) was
      achieved by including the simulated sound field of the probe rather than assuming
      straight acoustic beams and propagation according to ray acoustics.

PMID- 15478972
TI  - Directional synthetic aperture flow imaging.
AB  - A method for flow estimation using synthetic aperture imaging and focusing along
      the flow direction is presented. The method can find the correct velocity
      magnitude for any flow angle, and full color flow images can be measured using
      only 32 to 128 pulse emissions. The approach uses spherical wave emissions with a
      number of defocused elements and a linear frequency-modulated pulse (chirp) to
      improve the signal-to-noise ratio. The received signals are dynamically focused
      along the flow direction and these signals are used in a cross-correlation
      estimator for finding the velocity magnitude. The flow angle is manually
      determined from the B-mode image. The approach can be used for both tissue and
      blood velocity determination. The approach was investigated using both
      simulations and a flow system with a laminar flow. The flow profile was measured
      with a commercial 7.5 MHz linear array transducer. A plastic tube with an
      internal diameter of 17 mm was used with an EcoWatt 1 pump generating a laminar,
      stationary flow. The velocity profile was measured for flow angles of 90 and 60
      degrees. The RASMUS research scanner was used for acquiring radio frequency (RF)
      data from 128 elements of the array, using 8 emissions with 11 elements in each
      emission. A 20-micros chirp was used during emission. The RF data were
      subsequently beamformed off-line and stationary echo canceling was performed. The
      60-degree flow with a peak velocity of 0.15 m/s was determined using 16 groups of
      8 emissions, and the relative standard deviation was 0.36% (0.65 mm/s). Using the
      same setup for purely transverse flow gave a standard deviation of 1.2% (2.1
      mm/s). Variation of the different parameters revealed the sensitivity to number
      of lines, angle deviations, length of correlation interval, and sampling
      interval. An in vivo image of the carotid artery and jugular vein of a healthy 29
      year-old volunteer was acquired. A full color flow image using only 128 emissions
      could be made with a high-velocity precision.

PMID- 15478973
TI  - Axial strain calculation using a low-pass digital differentiator in ultrasound
      elastography.
AB  - In ultrasound elastography, tissue axial strains are calculated from the gradient
      of the estimated axial displacements. However, the common differentiation
      operation amplifies the noises in the displacement estimation, especially at high
      frequencies. In this paper, a low-pass digital differentiator (LPDD) is proposed
      to calculate the axial strain from the estimated tissue displacement. Several
      LPDDs that have been well developed in the field of digital signal processing are
      presented. The corresponding performances are compared qualitatively and
      quantitatively in computer simulations and in preliminary phantom and in vitro
      experiments. The results are consistent with the theoretical analysis of the
      LPDDs.

PMID- 15478974
TI  - Estimation of surface pose with a physically-based ultrasonic image model.
AB  - State-of-the-art approaches to shape analysis in medical images use a variety of
      sophisticated models for object shape. We have developed an image model that
      permits the application of these approaches to ultrasonic images, with detailed
      methods for representing rough surfaces. Our physically-based, probabilistic
      image model incorporates the combined effects of the system point-spread function
      (PSF), the tissue microstructure, and the gross tissue shape. At each image
      pixel, the amplitude mean and variance are computed directly from the model,
      characterizing the combined influence of shape, microstructure, and system PSF.
      Calculation of the SNR0 is used to further classify each pixel as Rayleigh- or
      non-Rayleigh-distributed. This characterization was used here to generate a data
      likelihood representing any set of images of a given surface by a probability
      density conditioned on the surface pose, or rotation and translation. The utility
      of this likelihood was demonstrated by applying maximum likelihood estimation to
      infer the pose of a cadaveric vertebra from simulated images of its surface.
      Successful results were achieved using derivative-based optimization algorithms
      for a data set of only three images. With a quasi-Newton BFGS algorithm, error in
      15 of 20 trials was less than 0.4 degrees in rotation and 0.2 mm in translation.
      Estimation was inaccurate in only 1 of 20 trials. These results illustrate the
      potential of a physically-based image model in a rigorous approach to image
      analysis and also serve as an example of quantitative assessment of the model via
      performance in a specific application.

PMID- 15478975
TI  - Contrast echocardiography for pulmonary blood volume quantification.
AB  - Pulmonary blood volume quantification is important both for diagnosis and for
      monitoring of the circulatory system. It requires employment of transpulmonary
      indicator dilution techniques, which are very invasive due to the need for double
      catheterization. This paper presents a new minimally invasive technique for blood
      volume quantification. An ultrasound contrast agent bolus is injected
      peripherally and detected by an ultrasound transducer in the central circulation.
      Several echocardiographic views permit simultaneous detection of contrast in
      different cardiac cavities and central vessels, and acoustic backscatter
      measurements produce multiple indicator dilution curves (IDCs). Contrast mean
      transit-time differences are derived from the IDC analysis and multiplied times
      cardiac output for the assessment of blood volumes between different detection
      sites. For pulmonary blood volume estimates, the right ventricle and the left
      atrium IDCs are measured. The mean transit time of the IDC is estimated by
      specific modelling. The Local Density Random Walk and the First Passage Time
      models were tested for IDC interpolation and interpretation. The system was
      validated in vitro for a wide range of flows. The results show very accurate
      volume measurements. The volume estimate determination coefficient is greater
      than 0.999 for both model fits. A preliminary study in patients shows promising
      results.

PMID- 15478976
TI  - The RF-powered surface wave sensor oscillator--a successful alternative to
      passive wireless sensing.
AB  - A novel, passive wireless surface acoustic wave (SAW) sensor providing a highly
      coherent measurand proportional frequency, frequency modulated (FM) with
      identification (ID) data and immune to interference with multiple-path signals is
      described. The sensor is appropriate for bandwidth-limited applications requiring
      high-frequency accuracy. It comprises a low-power oscillator, stabilized with the
      sensing SAW resonator and powered by the rectified radio frequency (RF) power of
      the interrogating signal received by an antenna on the sensor part. A few hundred
      microwatts of direct current (DC) power are enough to power the sensor oscillator
      and ID modulation circuit and achieve stable operation at 1.0 and 2.49 GHz.
      Reliable sensor interrogation was achieved over a distance of 0.45 m from a SAW
      based interrogation unit providing 50 mW of continuous RF power at 915 MHz. The 
      30 to -35 dBm of returned sensor power was enough to receive the sensor signal
      over a long distance and through several walls with a simple superheterodyne FM
      receiver converting the sensor signal to a low measurand proportional
      intermediate frequency and retrieving the ID data through FM detection. Different
      sensor implementations, including continuous and pulsed power versions and the
      possibility of transmitting data from several measurands with a single sensor,
      are discussed.

PMID- 15478977
TI  - Dyadic Green's functions of a laminar plate.
AB  - We introduce the concept of dyadic Green's functions of a laminar plate. These
      functions generalize classical Green's functions. In addition to relating
      displacements and stresses at the surface of a medium, they relate these
      quantities at both the top and the bottom surfaces of a medium of finite
      thickness and infinite extent in the transverse directions. We describe here the
      calculation of these functions in the spectral domain and provide some academic
      examples demonstrating their interest.

PMID- 15478978
TI  - Idealized analysis of SAW longitudinally coupled resonator filters.
AB  - A surface acoustic wave (SAW) longitudinally coupled resonator (LCR) filter
      consists of either two or three interdigital transducers located between two
      strongly reflecting gratings. The behavior of this structure is, in general, very
      complex because the transducers are of the single-electrode type, which gives
      strong electrode reflections. It is shown here that, for the filter passband, a
      number of realistic assumptions can be used to derive a very simple set of
      approximate relations for the device Y-matrix. The simplifications involve
      reciprocity, symmetry, and power conservation. The theory also uses the necessary
      fact that each grating, combined with its adjacent transducer, must have high
      directivity so that application of a voltage results in wave generation primarily
      toward the center of the device. For a three-transducer device, it is shown using
      symmetry that the central transducer behaves as if it were transparent, despite
      having strong electrode reflections. Hence, the device behaves as a single
      resonant cavity. The simple Y-matrix formulae are shown to agree very well with
      accurate results obtained by a coupling-of-modes (COM) analysis for both types of
      device. They also lead to simple formulae for the electrical loading required to
      obtain a flat, low-loss filter response. Equivalent circuits also are discussed.

PMID- 15478979
TI  - A new-style, slotted-cymbal transducer with large displacement and high energy
      transmission.
AB  - The cymbal transducer had more improved performances than the moonie transducer,
      but as with the moonie end caps, flexural motion of the cymbal end caps would
      cause high-tangential stresses, which could lead to loss of mechanical output
      energy. So, a new-style design, called slotted-cymbal transducer, is presented in
      this paper. The slotted-cymbal transducer released the tangential stresses by
      adopting a new-style, radial-slotted cymbal end caps. Through theoretical
      calculation and finite element analysis in collaboration with measurements, the
      slotted-cymbal transducer was demonstrated to possess high performances of
      displacement and energy transmission. This design would decrease the fundamental
      resonance frequencies of systems by different numbers of slots, and it would have
      more potential applications of low frequency and large displacement.

PMID- 15478980
TI  - Finite-element analysis of material and parameter effects in laser-based
      thermoelastic ultrasound generation.
AB  - Laser-based, thermoelastic transduction methods have potential in very high
      frequency (>50 MHz), high-density two-dimensional (2-D) arrays for a variety of
      very high-resolution superficial imaging applications, including in vivo tissue
      sectioning. Previous studies of these transducers generally have been based on
      experimental measurements or theoretical analyses using various simplifying
      assumptions. These theoretical models are mostly 1-D and best matched to simple
      geometries with a minimum number of component materials. In this work, we use a
      new thermoelastic solver in a commercially available finite-element analysis
      (FEA) software package to analyze multidimensional effects in laser-based devices
      of arbitrary geometry with the potential for use with arbitrary material
      properties. The FEA approach was verified first against experimental data.
      Thereafter, we explored the impact of various design variables, including laser
      spot size and laser penetration depth.

PMID- 15478981
TI  - Time-scale removal of "wall thump" in Doppler ultrasound signals: a simulation
      study.

PMID- 15478982
TI  - The search for spiritual/cultural competency in chaplaincy practice: five steps
      that mark the path.
AB  - Chaplains who are clinically trained and certified spiritual care professionals
      can make a unique contribution in today's increasingly pluralistic and global
      health care context with diverse religious, spiritual and cultural values,
      beliefs and practices. The author characterizes this contribution as
      spiritual/cultural competency. A self-defined web of meaning is unique to each
      person, comprised of a composite of values and beliefs, a fabric woven by way of
      one's life narrative. The proven approach of clinical learning, with heightened
      introspective and interpersonal awareness, serves as the chaplain's primary
      pathway to multi-spiritual/cultural competency, integrated with the exploration
      of context in a way not prioritized before. Utilizing sources from pastoral
      theology, anthropology and multicultural counseling, a five-step process of
      competency assessment is introduced and discussed with the aid of two cases.
      Knowing one's own spiritual/cultural grounding is the first step in this open
      ended search.

PMID- 15478983
TI  - Cultural diversity in pastoral care.
AB  - Fukuyama and Sevig are counseling psychologists who have a particular interest in
      the integration of spirituality into multicultural counseling and training. In
      this article the authors address the complexity of integrating religious and
      cultural diversity and spirituality into chaplaincy care in the context of an
      increasingly diverse society. By posing a series of questions, the authors
      systematically clarify definitions and meanings of culture, spirituality,
      cultural diversity and multiculturalism, multicultural and spiritual competencies
      in counseling, and ethical considerations. The authors discuss clinical
      applications in the context of a "spirituality and health movement," and provide
      suggestions for continuing professional development. The authors support the
      notion that multicultural engagement is spiritually synergistic, and encourage
      health care providers to communicate across professional disciplines to broaden
      and enrich discourse on these topics.

PMID- 15478984
TI  - Toward multicultural competencies for pastoral/spiritual care providers in
      clinical settings: response to Anderson, Fukuyama, and Sevig.

PMID- 15478985
TI  - Forging spiritual and cultural competency in spiritual care-givers: a response to
      Fukuyama and Sevig and Anderson.

PMID- 15478986
TI  - Definitions, obstacles, and standards of care for the integration of spiritual
      and cultural competency within health care chaplaincy.

PMID- 15478987
TI  - The chaplain's path in cultural and spiritual sensitivity: a response to
      Anderson, Fukuyama, and Sevig.

PMID- 15478989
TI  - Determinants of self-reported mental health using the British household panel
      survey.
AB  - BACKGROUND: The study of self-reported mental health is a fairly recent area for
      economists, although sociologists, psychologists and public health specialists
      have been studying it for years. One methodological problem with earlier research
      is that there are many unobserved characteristics of individuals that may be
      correlated with self-reported mental health. Neglecting these factors may lead to
      biased estimates of the effects of variables such as income, education, health,
      etc. Panel data enables us to control for unobserved individual specific effects,
      whereas a cross-section study or time series study cannot. AIMS OF THE STUDY:
      This paper examines the determinants of self-reported mental health in UK using
      data from the first eight waves of the British Household Panel Survey. In
      particular, we are interested in assessing the effect of education on self
      reported mental health which other studies have ignored. METHODS: The measure of
      self-reported mental health used in this paper is the General Health
      Questionnaire (GHQ). To account for the possible correlation between the
      unobserved individual effects and some explanatory variables, a Hausman Taylor's
      instrumental variables estimator (HT) is employed. In order to derive this
      estimator, one has to distinguish between variables that are correlated with the
      individual specific effects (endogenous) and variables which are uncorrelated
      with the individual specific effects (exogenous). This HT estimator also allows
      for estimating the parameters corresponding with time invariant variables such as
      education and ethnicity. RESULTS: The evidence presented here confirms that
      mental health scores mentioned on the GHQ are significantly related to job
      status, age, marital status and self-assessed health status. The results also
      show no evidence that income impacts on self-reported mental health. Ethnicity is
      also found to deteriorate self-reported mental health yet the effect is not
      significant. The results of this paper also show that education had no
      significant impact on self-reported mental health. IMPLICATIONS FOR MENTAL HEALTH
      POLICY: Issues related to unemployment and social cohesion may be relevant
      factors in the prevention of mental illness. Policies aimed at improving these
      factors have an impact on the mental health status of society. In consideration
      of the evidence of gender differential in mental health, mental health policies
      should take into account properly this issue. IMPLICATIONS FOR FURTHER RESEARCH:
      In order to draw definite conclusions, it is important to formally test the
      presence of attrition bias as well as expand the sample to include more waves.
      Still, we are concerned about the issue of weak correlation between the
      instruments and potential endogenous variables. Additionally, we have to bear in
      mind that inconsistent estimates may potentially occur if the partition of the
      variables in subsets of endogenous and exogenous is not correctly specified.
      These issues need further research. The estimation technique also presented in
      this paper may be applied to a wide range of health services research.

PMID- 15478990
TI  - Gender-based structural models of health care costs: alcohol use, physical
      health, mental health, and functioning.
AB  - BACKGROUND: Most models of health services use or costs include gender as a
      covariate, combining data for men and women in analyses. This strategy may
      obscure differences in underlying processes producing differential health care
      use by men and women, particularly in examinations of factors that affect health
      care use and differ by gender (e.g. alcohol consumption and depression). AIMS: To
      examine gender differences in the relationships between alcohol consumption,
      physical and mental health and functioning, and costs of health care. METHODS:
      The setting was Kaiser Permanente Northwest, a large non-profit group practice
      model HMO serving northwest Oregon and southwest Washington in the northwest
      United States. Primary (survey) and secondary (health plan records of service
      use; diagnoses from medical chart review) data were collected for random samples
      of health plan members in the period 1989-1993 (n = 5,669). Health plan
      administrative records of service use were used to estimate health care costs.
      Gender-specific latent structure models predicting health care costs were created
      using self-reported mental health, physical health, functioning, alcohol
      consumption, and prior-year health plan record-based diagnoses of depression and
      alcohol problems. RESULTS: Alcohol consumption and prior alcohol problems were
      directly related to health care costs, although in opposite directions, for both
      men and women. Alcohol consumption was negatively associated with costs, while
      prior alcohol problems predicted higher costs. Gender differences existed in the
      relationship between physical health and health care costs indirectly via
      drinking status. Prior depression had direct effects on increased health care
      costs, and this relationship was stronger for men than for women. The roles
      played by mental health symptoms were similar for men and women. Better mental
      health at the time of the survey was associated with reduced alcohol consumption
      or likelihood of consuming alcohol, but had no direct effects on later costs.
      Indirect effects of mental health were found via alcohol consumption.
      CONCLUSIONS: Gender plays an important role in the factors underlying total costs
      of health care, and gender differences in these relationships appear more common
      among those who consume alcohol. For both genders, alcohol use predicts lower
      health care costs in this light-to-moderate drinking population, although prior
      diagnoses of alcohol problems predict higher costs. The direct relationship
      between depression diagnosis and higher health care costs is stronger among men.

PMID- 15478991
TI  - Brief report - mental health research on low- and middle-income countries in
      indexed journals: a preliminary assessment.
AB  - BACKGROUND: Mental health research focused on low- and middle-income (LAMI)
      countries is needed in view of the burden of neuropsychiatric diseases and the
      deficiency of mental health resources in these countries. AIMS OF THE STUDY: To
      examine whether mental health research publications on LAMI countries address
      issues that are likely to influence public mental health. METHOD: Four databases
      were searched for years 2000 and 2001 with subject headings related to mental
      disorders, mental health services, somatic therapies and psychotherapy. Countries
      were categorized into income groups according to World Bank (2000) criteria. The
      title, index words and abstracts were reviewed. RESULTS: Almost 55% of
      publications related to ten LAMI countries. One sixth of research publications
      related to services/policies, but less than 1% were devoted to economic
      evaluation. Affective disorders, self-inflicted injuries and mental retardation
      were under-researched. DISCUSSION: The geographic spread of internationally
      accessible mental health research publications is limited. Moreover, publications
      from LAMI countries often do not address public mental health issues. Use of a
      single rater might have led to some arbitrariness in classification of articles
      and some relevant articles would have been missed because of our inability to
      include all relevant databases. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE:
      Sustained support by various stakeholders is needed for research that can inform
      mental health care provision and use in LAMI countries. IMPLICATIONS FOR HEALTH
      POLICIES: Scientific research can inform mechanisms that influence policy and
      public health if adequate attention is paid to dissemination of findings to end
      users. IMPLICATIONS FOR FURTHER RESEARCH: There is a need to focus research in
      LAMI countries on mental health conditions causing high burden that are currently
      under-researched (e.g. depression, mental retardation, self-inflicted injuries),
      policy and service issues, and mental health economics.

PMID- 15478992
TI  - Adolescent propensity for depressed mood and help seeking: race and gender
      differences.
AB  - BACKGROUND: Studies investigating the correlates of adolescent depression and
      suicidal tendencies have found that the probability of such tendencies vary by
      race and gender. However, while there exists evidence that most adolescents
      suffering from the above problems fail to seek (and obtain) help, the role of
      race and gender in determining the propensity to seek help for depression remains
      largely unexplored. AIMS OF STUDY: The study uses data from the 1996 round of
      Health Behavior in School-Aged Children' (HBSC), USA, which surveys a
      representative sample of more than 9000 adolescents enrolled in grades 6-10.
      Respondents are asked if they suffered from persistent depressed moods (lasting
      two weeks or more) over the past year, and whether they sought help while
      suffering from depressed mood, and if so, from whom. Questions are also asked
      about whether the respondent had self-injury ideation or actually attempted self
      injury. Demographic and other information on respondents is also provided. The
      primary aim is to test whether there are significant differences between genders,
      and between non-Hispanic whites, non-Hispanic blacks, Hispanics and Asians in the
      likelihood of seeking help, and from whom, when depressed. Gender and race
      ethnicity differences in the likelihood of being depressed are also explored to
      find if they correspond to results in the extant literature. METHODS: Multinomial
      logit models are used to estimate the likelihood of being depressed or at self
      injury risk, and help-seeking behavior in event of depressed mood. Models are
      estimated for the full-sample and sub-samples who report depressed mood or are at
      self-injury risk. In addition to race and gender, all models control for
      additional demographic characteristics such as age, family structure, and family
      socio-economic status. RESULTS: Adolescent females are significantly more likely
      than adolescent males to suffer from depressed mood. However, adolescent males
      are less likely to ask for help than females (odds ratio: 0.72). All minority
      groups are more likely to suffer from depressed mood compared to non-Hispanic
      whites, but blacks are at lower self-injury risk. Blacks and Asians are
      especially prone not to ask for help, with the problem being particularly acute
      in case of black males and Asian males. DISCUSSION: The lower propensity of
      adolescent males to seek help for depression compared to females are in keeping
      with previous research. However, predicted values show that the majority of males
      and females with depressed mood or at self-injury risk do not seek help from
      anyone. Certain racial groups are also at greater risk for not asking for help
      for depression. This may have implications regarding racial differences in
      suicide rates, as well as racial differences in future life outcomes. The study
      suffers from the drawback that because the survey is confined to those enrolled
      in school, adolescents who are institutionalized for mental health problems or
      who have dropped out of school due to problems related to depression are not
      represented in it. IMPLICATIONS FOR HEALTH POLICIES: There have been efforts in
      the USA to educate the population about the problems of adolescent depression.
      However, the above results suggest that it may be useful to have additional
      educational efforts targeted at specific population groups, to educate them about
      the risks associated with depression, help overcome any stigma associated with
      depression and encourage help-seeking when suffering from depressed mood.
      IMPLICATIONS FOR FURTHER RESEARCH: A number of directions of future research are
      suggested. It would be useful to obtain information on the outcomes of help
      seeking - whether it actually led to obtaining help. It would also be useful to
      know the probability of an adolescent being diagnosed with depressed mood
      (perhaps by a primary care physician) even without actively seeking help.
      Regarding the racial differences, it would be useful to examine the extent to
      which such differences arise from immigration status, and also to have more
      extensive information about attitudes, familial expectations, religiosity,
      community ties, confidence in the medical system and other factors, so as to
      analyze further why some races are more prone to depression and averse to seeking
      help for depression than others. Finally, it would be useful to periodically
      revisit this topic with more contemporary data to see whether recent efforts at
      awareness raising has increased the odds of help-seeking among adolescents with
      depressed mood.

PMID- 15478993
TI  - Multiresidue determination of pesticides in malt beverages by capillary gas
      chromatography with mass spectrometry and selected ion monitoring.
AB  - A method was developed to determine pesticides in malt beverages using solid
      phase extraction on a polymeric cartridge and sample cleanup with a MgSO4-topped
      aminopropyl cartridge, followed by capillary gas chromatography with electron
      impact mass spectrometry in the selected ion monitoring mode [GC-MS(SIM)]. Three
      GC injections were required to analyze and identify organophosphate,
      organohalogen, and organonitrogen pesticides. The pesticides were identified by
      the retention times of peaks of the target ion and qualifier-to-target ion
      ratios. GC detection limits for most of the pesticides were 5-10 ng/mL, and
      linearity was determined from 50 to 5000 ng/mL. Fortification studies were
      performed at 10 ng/mL for three malt beverages that differ in properties such as
      alcohol content, solids, and appearance. The recoveries from the three malt
      beverages were greater than 70% for 85 of the 142 pesticides (including isomers)
      studied. The data showed that the different malt beverage matrixes had no
      significant effect on the recoveries. This method was then applied to the
      screening and analysis of malt beverages for pesticides, resulting in the
      detection of the insectide carbaryl and the fungicide dimethomorph in real
      samples. The study indicates that pesticide levels in malt beverages are
      significantly lower than the tolerance levels set by the United States
      Environmental Protection Agency for malt beverage starting ingredients. The use
      of the extraction/cleanup procedure and analysis by GC-MS(SIM) proved effective
      in screening malt beverages for a wide variety of pesticides.

PMID- 15478994
TI  - Improved normal-phase high-performance liquid chromatography procedure for the
      determination of carotenoids in cereals.
AB  - Besides the health benefits associated with whole-grain consumption, cereals are
      recognized sources of health-enhancing bioactive components such as carotenoids,
      which are a group of yellow pigments involved in the prevention of many
      degenerative diseases and which have been used for a long time as indicators of
      the color quality of durum wheat and pasta products. This work reports a fast,
      sensitive, and selective procedure for the extraction and determination of
      carotenoids from cereals and cereal byproducts. The method involves sample
      saponification and extraction followed by normal-phase high-performance liquid
      chromatography, allowing the separation of the main carotenoids pigments of
      cereals, especially lutein and zeaxanthin. An application of the established
      method to various species of cereals and cereal byproducts is also shown. The
      highest carotenoid levels were found in maize (approximately 11.14 mg/kg of dry
      weight), which contains high amounts of beta-cryptoxanthin (2.40 mg/kg of dry
      weight), and, among the cereals considered, has the highest content of zeaxanthin
      (6.43 mg/kg of dry weight) and alpha+beta-carotene (1.44 mg/kg of dry weight).
      With the exception of maize, lutein is the main compound found (from 0.23 to 2.65
      mg/kg of dry weight in oat and durum wheat, respectively). Moreover, whereas
      alpha+beta-carotene and zeaxanthin are principally localized in the germ, lutein
      is equally distributed along the kernel.

PMID- 15478995
TI  - Determination of volatile components in ginger using gas chromatography-mass
      spectrometry with resolution improved by data processing techniques.
AB  - Ginger is widely used as either a food product or an herbal medicine in the
      world. In this paper, a method was developed for determining volatile components
      in essential oils from both dried and fresh ginger by use of gas chromatography
      mass spectrometry (GC-MS) and chemometric approaches. With the resolution
      improvement by chemometric methods upon two-dimensional data from GC-MS, the
      drifting baseline can be corrected. In addition, the peak purity can be assessed
      and the number of chemical components and their stepwise elution in the peak
      clusters can be identified. The peak clusters investigated are then resolved into
      pure chromatograms and related mass spectra for each of the components involved.
      Finally, with the pure chromatograms and related mass spectra obtained, the
      chemical components can be qualitatively identified based on the similarity
      searches in the MS databases and the chromatographic retention times.
      Quantitative determination can be conducted using the overall volume integration
      approach. The results showed that 140 and 136 components were separated and that
      74 and 75 of them were tentatively identified, which accounted for about 62.82
      and 47.11% of the total relative content for dried and fresh ginger,
      respectively. In comparison with the chromatographic fingerprints of essential
      oils from dried and fresh ginger, 60 of the volatile components determined match
      with each other. The study demonstrated that the use of chemometric resolution
      based on two-dimensional data can mathematically enhance the separation ability
      of GC-MS and assist qualitative and quantitative determination of chemical
      components separated from complicated practical systems such as foods, herbal
      medicines, and environmental samples.

PMID- 15478996
TI  - Monitoring of the fermentation media of citric acid by the trimethylsilyl
      derivatives of the organic acids formed.
AB  - In this approach, a derivatization method is described for monitoring of organic
      acids in fermentation media without any separation step. The aqueous phase of
      fermentation media was evaporated and heated in a silylation reagent to form
      trimethylsilyl (TMS) derivatives. The silylated compounds are analyzed by 29Si
      nuclear magnetic resonance (29Si NMR) and gas chromatography-mass spectrometry
      (GC-MS). 29Si NMR can qualitatively monitor the components produced in the Krebs
      cycle. Quantification of these compounds is investigated by using selected ion
      monitoring mode of mass spectrometry. In this mode, mass to charge (m/z) values
      of their [M - 15]+ ions, which are 465, 275, 247, 221, 335, 251, and 313 of TMS
      derivatives of citric, alpha-ketoglutaric, succinic, fumaric, l-malic,
      oxaloacetic, and palmitic (as an internal standard), acids, respectively, are
      used. The limit of detection and the linear working range for derivatized citric
      acid were found to be 0.1 mg L(-1) and 10-3 x 10(4) mg L(-1). The relative
      standard deviation of the method for five replicates was 2.1%. The average
      recovery efficiency for citric acid added to culture media was approximately
      97.2%. Quantitative results of GC-MS are compared with those obtained by an
      ultraviolet-visible method.

PMID- 15478997
TI  - Gas chromatographic quantification of major volatile compounds and polyols in
      wine by direct injection.
AB  - Methanol, propanol, isobutanol, isoamyl alcohol, 2-phenylethanol, acetaldehyde,
      1,1-diethoxyethane, acetoin, ethyl acetate, ethyl lactate, and ethyl succinate
      and the polyols 2,3-butanediol (levo and meso forms) and glycerol were quantified
      by direct injection of wine samples. Linear responses over the usual
      concentration ranges for these compounds and r2 values from 0.9932 to 0.9998 were
      obtained. The confidence limits for the mean values ranged from 2.34% for diethyl
      succinate to 8.52% for 1,1-diethoxyethane, both at a probability level of 0.05.
      Relative errors ranged from 8 to 10% for the polyols and 1,1-diethoxyethane and
      were all less than 5% for alcohols and acetaldehyde. The proposed method is
      useful with a view to identifying relationships between alcoholic fermentation
      byproducts and controlling biological or chemical aging in wines.

PMID- 15478998
TI  - Extending the working range of immunoanalysis by exploitation of two monoclonal
      antibodies.
AB  - A newly established rat monoclonal antibody (mAb) for isoproturon, namely, IOC
      10G7, is described. This mAb shows a standard curve for isoproturon in phosphate
      buffered saline with a test midpoint of 5.5 +/- 1.8 microg/L (n = 15). In
      combination with the formerly developed mAb IOC 7E1, IOC 10G7 can be exploited to
      extend the working range for the analysis of isoproturon. Both antibodies were
      formatted into a competitive enzyme-linked immunosorbent assay (ELISA), using the
      same enzyme-tracer. MAb IOC 7E1 and mAb IOC 10G7 have different affinities for
      the target compound, but the signal-response curves of the single antibodies
      overlap. Cross-reactivity (CR) patterns of both antibodies are comparable,
      showing the highest CR for the metabolite 1-(4-isopropylphenyl)-3-methylurea (IOC
      10G7, 9%; IOC 7E1, 19%). The system described here includes the combined, but
      individual, usage of both assays on one microtiter plate, as well as the strategy
      for mixing the two antibodies for the utilization in one assay. When standards
      are performed in Milli-Q water, the working range for isoproturon with the
      individual ELISAs using mAb IOC 7E1 is from 0.01 to 1 microg/L (test midpoint =
      0.11 +/- 0.03 microg/L; n = 17) and with IOC 10G7, it is 1-100 microg/L (test
      midpoint = 10.3 +/- 1.6 microg/L; n = 32). The working range with mixed
      antibodies is usually on the order of 0.03-30 microg/L (test midpoint = 0.5 +/-
      0.2 microg/L; n = 17). These strategies (mAbs individually and mixed) cover a
      range of 4 and 3 orders of magnitude, respectively. As a demonstration, water
      samples of different origins and an extract of mixed sediment were analyzed. The
      advantages of these strategies are discussed.

PMID- 15478999
TI  - Degradation studies on benzoxazinoids. Soil degradation dynamics of 2,4-dihydroxy
      7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA) and its degradation products,
      phytotoxic allelochemicals from gramineae.
AB  - Benzoxazinoids have been described as important allelochemicals from Gramineae as
      well as Acanthaceae, Rannunculaceae, and Scrophulariaceae plants. Several
      bioactivities have been described and evaluated for these compounds, including
      fungistatic, antifeedant, and phytotoxic. In ongoing studies about
      allelochemicals as natural herbicide models, the description of soil dynamics in
      phytotoxic agents has high importance, because the possible biotransformations
      developed by soil microorganisms could yield compounds with modified biological
      properties, affecting the overall allelopathic capability of the producer plant
      in a direct manner. Thus, a complete degradation study has been carried out for
      2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA) and 6
      methoxybenzoxazolin-2(3H)-one (MBOA) in two soils cultivated with Triticum
      aestivum L. varieties (cv. Astron and cv. Ritmo). The main purpose was to
      identify degradation products and to elucidate biotransformation dynamics.
      Results show DIMBOA to degrade rapidly, yielding MBOA in both studied soils at
      different doses (t(1/2) = 31 +/- 1 h, n = 12) and reaching high conversions (80
      +/- 4 h, n = 42). MBOA, an intermediate in the degradation pathway from DIMBOA to
      2-amino-7-methoxy-3H-phenoxazin-3-one (AMPO), was more resistant toward
      biodegradation (t(1/2) = 5 +/- 1 days, n = 6). MBOA showed maximum conversions at
      a dose of 250 mg/kg of soil (36 +/- 3 days, n = 6). Soil belonging to T. aestivum
      cv. Ritmo crops showed higher degradation capacity than cv. Astron soil. AMPO was
      the final degradation product observed for DIMBOA in the soils and experimental
      conditions selected. Consequences for activity and stability of these compounds
      in relation to allelopathy are discussed.

PMID- 15479000
TI  - In vivo antifungal activity of the essential oil of Bupleurum gibraltarium
      against Plasmopara halstedii in sunflower.
AB  - The antifungal activity of the essential oil of the aerial parts of Bupleurum
      gibraltarium was evaluated against Plasmopara halstedii. Fungus spores were
      inoculated in sunflower seedlings, previously treated with several essential oil
      solutions, and the sporulation percentage was measured after an 11-day treatment.
      The oil at a concentration of 5.0 mL/L clearly inhibited the fungus sporulation.
      The contact between fungus sporangia and essential oil was minimized, so it seems
      that the oil pretreatment could activate the defense response of the sunflower
      seedlings against the pathogen invasion. The main compounds in the oil were
      sabinene (31.1%), alpha-pinene (15.6%), and 2,3,4-trimethylbenzaldehyde (10.9%),
      among a total of 65 components identified.

PMID- 15479001
TI  - Microbial metabolites of ingested caffeic acid are absorbed by the monocarboxylic
      acid transporter (MCT) in intestinal Caco-2 cell monolayers.
AB  - It was previously reported that m-coumaric acid, m-hydroxyphenylpropionic acid
      (mHPP), and 3,4-dihydroxyphenylpropionic acid (DHPP) are major metabolites of
      ingested caffeic acid formed by gut microflora and would be transported by the
      monocarboxylic acid transporter (MCT). We have directly measured their absorption
      characteristics in Caco-2 cells using a coulometric detection method involving
      HPLC-ECD. The proton-coupled directional transport of m-coumaric acid, mHPP, and
      DHPP was observed, and the transport was inhibited by an MCT substrate. The
      permeation of m-coumaric acid and mHPP was concentration-dependent and saturable:
      The Michaelis constant for m-coumaric acid and mHPP was 32.5 and 12.9 mM,
      respectively, and the maximum velocity for m-coumaric acid and mHPP was 204.3 and
      91.2 nmol (min)(-1) (mg protein)(-1), respectively. By contrast, the permeation
      of DHPP was nonsaturable even at 30 mM and was inversely correlated with the
      paracellular permeability of Caco-2 cells. Our results demonstrate that these
      compounds are absorbed by the MCT, although DHPP is mainly permeated across Caco
      2 cells via the paracellular pathway. MCT-mediated absorption of phenolic
      compounds per se and their colonic metabolites would exert significant impact on
      human health.

PMID- 15479002
TI  - Antioxidant activity of ferulic acid alkyl esters in a heterophasic system: a
      mechanistic insight.
AB  - The antioxidant activity of some esters of ferulic acid with the linear fatty
      alcohols C7, C8 (branched and linear), C9, C11, C12, C13, C15, C16, and C18 has
      been studied in homogeneous and heterogeneous phases. Whereas in homogeneous
      phase all of the alkyl ferulates possessed similar radical-scavenging abilities,
      in rat liver microsomes they showed striking differences, the more effective
      being C12 (7) (IC50 = 11.03 M), linear C8 (3) (IC50 = 12.40 microM), C13 (8)
      (IC50 = 18.60 microM), and C9 (5) (IC50 = 19.74 microM), followed by C7 (2), C15
      (9), C11 (6), branched C8 (4), C16 (10), and C18 (11) (ferulic acid was the less
      active, IC50 = 243.84 microM). All of the molecules showed similar partition
      coefficients in an octanol-buffer system. Three-dimensional studies (NMR in
      solution, modeling in vacuo) indicate that this behavior might be due to a
      different anchorage of the molecules with the ester side chain to the microsomal
      phospholipid bilayer and to a consequent different orientation/positioning of the
      scavenging phenoxy group outside the membrane surface against the flux of oxy
      radicals.

PMID- 15479003
TI  - Effective separation of potent antiproliferation and antiadhesion components from
      wild blueberry (Vaccinium angustifolium Ait.) fruits.
AB  - Extracts from wild blueberry (Vaccinium angustifolium Ait.) were separated into
      proanthocyanidin-rich fractions using liquid vacuum and open column
      chromatography on Toyopearl and Sephadex LH-20, respectively. Fractions were
      characterized using analytical tools including mass spectrometry and NMR
      spectroscopy; fraction composition was correlated with bioactivity using
      antiproliferation and antiadhesion in vitro assays. There was a significant
      positive correlation between proanthocyanidin content of different fractions and
      biological activity in both the antiproliferation and antiadhesion assays. Two
      fractions containing primarily 4-->8-linked oligomeric proanthocyanidins with
      average degrees of polymerization (DPn) of 3.25 and 5.65 inhibited adhesion of
      Escherichia coli responsible for urinary tract infections. Only the fraction with
      a DPn of 5.65 had significant antiproliferation activity against human prostate
      and mouse liver cancer cell lines. These findings suggest both antiadhesion and
      antiproliferation activity are associated with high molecular weight
      proanthocyanidin oligomers found in wild blueberry fruits.

PMID- 15479004
TI  - Bioactive lignans from a cultivar of Helianthus annuus.
AB  - A bioassay-guided fractionation of water extracts from Helianthus annuus cv. SH
      222 was carried out. Ten lignans and a phenylpropanoid were isolated from the
      polar bioactive fractions of H. annuus. This study is the first to report lignans
      as constituents of sunflower and is the first time that tanegool has been
      isolated as a natural aglycone. Additionally, we report biological activities of
      the isolated compounds. The general bioactivity has been evaluated using the
      wheat coleoptiles bioassay. The phytotoxic activities of compounds pinoresinol,
      lariciresinol, dihydro-dehydrodiconiferilic alcohol, and l-(4'-hydroxy-3'
      methoxyphenyl)-2-[4' '-(3hydroxypropyl)-2' '-methoxyphenoxy]propane-l,3-diol were
      also evaluated in a bioassay on the standard target species. The structure
      activity relationships are discussed.

PMID- 15479005
TI  - Influence of emulsifier type and content on functional properties of
      polysaccharide lipid-based edible films.
AB  - This study investigates the effect of different types of surfactant (glycerol
      monostearate, Tween 60, and Tween 80) on water vapor permeability (WVP), tensile
      strength (TS), percentage elongation at breaking (E), and structure of an
      emulsified edible film composed of cornstarch, methylcellulose, and cocoa butter
      or soybean oil. Factorial designs at two levels were used to analyze the effect
      of emulsifier (EM) and lipid content on the functional properties of film.
      Results showed that the effects of independent variables on WVP, TS, and E depend
      on surfactant and lipid type. The presence of EM significantly decreased the WVP
      of cocoa butter films but did not improve the barrier or mechanical properties of
      soybean oil-based film.

PMID- 15479006
TI  - Preparation of soybean oil-based greases: effect of composition and structure on
      physical properties.
AB  - Vegetable oils have significant potential as a base fluid and a substitute for
      mineral oil in grease formulation. Preparation of soybean oil-based lithium
      greases using a variety of fatty acids in the soap structure is discussed in this
      paper. Soy greases with lithium-fatty acid soap having C12-C18 chain lengths and
      different metal to fatty acid ratios were synthesized. Grease hardness was
      determined using a standard test method, and their oxidative stabilities were
      measured using pressurized differential scanning calorimetry. Results indicate
      that lithium soap composition, fatty acid types, and base oil content
      significantly affect grease hardness and oxidative stability. Lithium soaps
      prepared with short-chain fatty acids resulted in softer grease. Oxidative
      stability and other performance properties will deteriorate if oil is released
      from the grease matrix due to overloading of soap with base oil. Performance
      characteristics are largely dependent on the hardness and oxidative stability of
      grease used as industrial and automotive lubricant. Therefore, this paper
      discusses the preparation methods, optimization of soap components, and
      antioxidant additive for making soy-based grease.

PMID- 15479007
TI  - Enriched accumulation and biotransformation of selenium in the edible seaweed
      Laminaria japonica.
AB  - Accumulations of selenium in kelp Laminaria japonica cultured in seawater was
      achieved by adding selenite (Na2SeO3) with or without N-P (NaNO3 + NaH2PO4)
      nutrients at different concentrations. Biotransformation of selenium in the kelp
      was investigated through measuring the selenium of biological samples and
      different biochemical fractionations. The results showed that the optimal
      selenite-enrichment concentration is 200 mg L(-1), which can allow the kelp to
      accumulate a total selenium content from 0.51 +/- 0.15 to 26.23 +/- 3.12 microg
      g(-1) of fresh weight (fw). Selenium composition analysis of kelp (control group)
      showed that selenium is present as organic selenium, which is up to 86.22% of the
      total selenium, whereas inorganic selenium is barely 4.85%. When L. japonica was
      exposed for 56 h in seawater containing 200 mg L(-1) Na2SeO3, the organic
      selenium was 16.70 microg g(-1) of fw (68.23%) and inorganic selenium was 4.71
      microg g(-1) of fw (19.26%). The capability of accumulation of selenium was
      further enhanced by adding N-P nutrients to the selenite-enriched medium. Total
      selenium is increased to be 33.65 microg g(-1) of fw at optimal concentration of
      N-P nutrient (150 mg L(-1) NaNO3 and 25 mg L(-1) NaH2PO4), whereas the inorganic
      selenium was not increased and remained at 4.597 microg g(-1) of fw (13.36%), and
      the increased part of selenium was organic selenium. This implied that kelp L.
      japonica could effectively transform inorganic selenium into organic selenium
      through metabolism.

PMID- 15479008
TI  - Metabolism of gallic acid and catechin by Lactobacillus hilgardii from wine.
AB  - The ability of Lactobacillus hilgardii 5w to metabolize gallic acid and catechin
      was evaluated. It was grown in a complex medium containing gallic acid or
      catechin. The metabolites were analyzed by high-performance liquid chromatography
      and identified by comparing the retention times and spectral data with the
      standards of a database. In gallic acid-grown cultures, gallic acid, pyrogallol,
      catechol, protocatechuic acid, p-hydroxybenzoic acid, p-hydroxybenzaldehyde, and
      p-hydroxybenzyl alcohol were detected. In catechin-grown cultures, catechin,
      gallic acid, pyrogallol, catechol, p-hydroxybenzoic acid, acetovanillone, and
      homovanillic acid were detected. This work presents evidence of gallic acid and
      catechin degradation by L. hilgardii from wine.

PMID- 15479009
TI  - Comparison of changes in the secondary structure of unheated, heated, and high
      pressure-treated beta-lactoglobulin and ovalbumin proteins using fourier
      transform raman spectroscopy and self-deconvolution.
AB  - Changes in protein secondary structure and conformation of ovalbumin and beta
      lactoglobulin (15% protein w/w) were investigated by Fourier transform Raman
      spectroscopy and self-deconvolution. The amounts of alpha-helix, beta-sheets,
      random coil, and beta-turns in native beta-lactoglobulin were 15, 54, 6, and 25%,
      respectively, and those for ovalbumin (41, 34, 13, and 12%) compared well with
      published values obtained by X-ray crystallography. The proteins were heated at
      90 degrees C for 30 min and high-pressure-treated at 600 MPa for 20 min. Heating
      increased beta-sheet structures in both proteins at the expense of alpha-helix;
      for beta-lactoglobulin beta-sheet structures increased from 54 to 70% and for
      ovalbumin, from 34 to 54%. Random coil increased from 6% in the native protein to
      30% in high-pressure-treated beta-lactoglobulin. However, for ovalbumin, the
      contribution from beta-turns doubled in high-pressure-treated samples, with
      little change in random coil. Further examination of the deconvoluted amide I
      band in heated samples revealed several component bands. Bands at 1626 and 1682
      cm(-1) for ovalbumin and at 1625 and 1680 cm(-1) for beta-lactoglobulin were
      observed and are associated with aggregated, intermolecular beta-sheet (beta
      aggregation), indicative of heat denaturation. The band seen at 1632-1640 cm(-1)
      corresponded to intramolecular beta-sheet structures, whereas the band at 1625
      cm(-1) is associated with exposed beta-sheets (for example, beta-strands with
      strong hydrogen bonding that are not part of the core of beta-sheets). In high
      pressure-treated samples bands were also observed at 1628 and 1680 cm(-1) for
      ovalbumin and at 1626 and 1684 cm(-1) for beta-lactoglobulin, suggesting
      involvement of beta-sheet structures in protein aggregation. Raman bands were
      observed at 1665-1670 cm(-1) for ovalbumin and at 1663-1675 cm(-1) for beta
      lactoglobulin due to random coil structures. The bands at 1650-1660 cm(-1) due to
      alpha-helices were observed in both heated and high-pressure-treated samples. In
      addition, in heated samples of both ovalbumin and beta-lactoglobulin, peak
      intensity increased for beta-sheet in the amide III region, 980-990 cm(-1), and
      decreased for helix structures (900-960 cm(-1)). In contrast, there was no peak
      at 1240 cm(-1) (amide III beta-sheet structures) in either high-pressure-treated
      ovalbumin or beta-lactoglobulin, suggesting that high-pressure denaturation at
      600 MPa for 20 min is less extensive than heat denaturation at 90 degrees C for
      30 min.

PMID- 15479010
TI  - Occurrence of 6-methoxymellein in fresh and processed carrots and relevant effect
      of storage and processing.
AB  - The occurrence of 6-methoxymellein (6-MM) in fresh and conventionally processed
      carrot products (for a total of 176 samples) marketed in European locations and
      the effect of Alternaria spp. infection and storage conditions on 6-MM
      accumulation were investigated. 6-MM was found in 78% of tested samples with
      levels ranging from 0.02 to 76.00 microg/g, with only 1 of 79 fresh carrots
      exceeding the "just noticeable difference" level for 6-MM. Storage of carrots at
      1 degree C was suitable to maintain low levels of 6-MM for a period of at least
      17 weeks. No effect of Alternaria spp. infection was observed on 6-MM occurrence.
      The fate of 6-MM during carrot juice processing was also investigated by using
      different enzyme formulations for maceration and blanching procedures. Levels of
      6-MM in blanched carrots obtained by boiling water or steam treatment were
      reduced by 69 or 33%, respectively, as compared to fresh carrots. No decrease in
      6-MM levels was observed after maceration with pectinolytic enzyme preparations
      (Rapidase Carrot Juice and Ultrazym AFP-L). A reduction of 6-MM by 85 or 94% was
      obtained after the entire cycle of carrot juice processing, depending on the
      blanching procedure used.

PMID- 15479011
TI  - Effects of sterol structure, temperature, and lipid medium on phytosterol
      oxidation.
AB  - Factors contributing to the oxidative stability of phytosterols were studied.
      Unsaturated stigmasterol and saturated sitostanol were used as model compounds
      and were heated at different temperatures in different lipid matrices for various
      periods of time. Accumulations of the major secondary oxidation products were
      used as a marker of the stability of heated compounds, and the products were
      analyzed by gas chromatography-mass spectrometry. The results showed that both
      temperature and heating time, as well as sterol structure and lipid matrix
      composition, affected phytosterol oxidation. In particular, the interactions
      between different lipid matrices and temperatures had drastic effects on the
      total contents of the phytosterol oxides formed and also on the reaction pathways
      of oxidation. During heating at high temperatures for prolonged periods, >20% of
      stigmasterol was oxidized. At moderate temperatures the oxidation of stigmasterol
      was rather slow. Sitostanol oxide contents were low under all heating conditions
      studied.

PMID- 15479012
TI  - Quantitative measurement of negligible trypsin inhibitor activity and nutrient
      analysis of guar meal fractions.
AB  - A complete nutrient characterization of three possible products of guar bean
      processing does not apparently exist in the literature. Guar meal is a high
      protein byproduct produced during extraction of galactomannan gum from the guar
      bean. During the extraction process, two fractions are produced (germ and hull).
      Germ and hull fractions are usually combined to form the marketed product, guar
      meal. Analyses characterized the nutrient, trypsin inhibitor, and galactomannan
      gum content of the three guar meal byproducts to determine which fraction is more
      valuable as an ingredient in poultry diets. Analyses indicated that the germ
      fraction is most appropriate for inclusion in poultry diets. Trypsin inhibitor
      activity previously reported as an antigrowth factor associated with guar meal
      was negligible and not considered to be a significant factor limiting its use in
      poultry feeds.

PMID- 15479013
TI  - Lignins and ferulate-coniferyl alcohol cross-coupling products in cereal grains.
AB  - Plant cell walls containing suberin or lignin in the human diet are conjectured
      to protect against colon cancer. To confirm the existence of authentic lignin in
      cereal grain dietary fibers, the DFRC (derivatization followed by reductive
      cleavage) method was applied to different cereal grain dietary fibers. By
      cleavage of diagnostic arylglycerol-beta-aryl (beta-O-4) ether linkages and
      identification of the liberated monolignols, it was ascertained that lignins are
      truly present in cereal grains. From the ratios of the liberated monolignols
      coniferyl alcohol and sinapyl alcohol, it is suggested that lignin compositions
      vary among cereals. Furthermore, dimeric cross-coupling products, comprising
      ferulate and coniferyl alcohol, were identified in most cereal fibers
      investigated. These ferulate 4-O-beta- and 8-beta-coniferyl alcohol cross-coupled
      structures indicate radical cross-coupling of polysaccharides to lignin
      precursors via ferulate.

PMID- 15479014
TI  - Influence of organic versus conventional agricultural practice on the antioxidant
      microconstituent content of tomatoes and derived purees; consequences on
      antioxidant plasma status in humans.
AB  - The present study aims first to compare the antioxidant microconstituent contents
      between organically and conventionally grown tomatoes and, second, to evaluate
      whether the consumption of purees made of these tomatoes can differently affect
      the plasma levels of antioxidant microconstituents in humans. When results were
      expressed as fresh matter, organic tomatoes had higher vitamin C, carotenoids,
      and polyphenol contents (except for chlorogenic acid) than conventional tomatoes.
      When results were expressed as dry matter, no significant difference was found
      for lycopene and naringenin. In tomato purees, no difference in carotenoid
      content was found between the two modes of culture, whereas the concentrations of
      vitamin C and polyphenols remained higher in purees made out of organic tomatoes.
      For the nutritional intervention, no significant difference (after 3 weeks of
      consumption of 96 g/day of tomato puree) was found between the two purees with
      regard to their ability to affect the plasma levels of the two major
      antioxidants, vitamin C and lycopene.

PMID- 15479015
TI  - Study of flavonoids of Sechium edule (Jacq) Swartz (Cucurbitaceae) different
      edible organs by liquid chromatography photodiode array mass spectrometry.
AB  - A liquid chromatography-mass spectrometry (LC-MS)-based method was developed for
      the characterization of flavonoids from Sechium edule (Jacq) Swartz
      (Cucurbitaceae) edible organs, a plant cultivated since pre-Colombian times in
      Mexico where the fruit is called chayote. Chayote is used for human consumption
      in many countries; in addition to the fruits, stems, leaves and the tuberous part
      of the roots are also eaten. Eight flavonoids, including three C-glycosyl and
      five O-glycosyl flavones, were detected, characterized by nuclear magnetic
      resonance spectroscopic data, and quantified in roots, leaves, stems, and fruits
      of the plant by LC-photodiode array-MS. The aglycone moieties are represented by
      apigenin and luteolin, while the sugar units are glucose, apiose, and rhamnose.
      The results indicated that the highest total amount of flavonoids was in the
      leaves (35.0 mg/10 g of dried part), followed by roots (30.5 mg/10 g), and
      finally by stems (19.3 mg/10 g).

PMID- 15479016
TI  - Distribution of ascorbic acid in potato tubers and in home-processed and
      commercial potato foods.
AB  - HPLC was used to analyze the content of ascorbic acid (AA) in tubers of four
      Korean potato cultivars (Chaju, Sumi, Deso, and Dejima), in a series of baked,
      boiled, braised, fried, microwaved, pressure-cooked, and sauteed potato slices
      from the Dejima cultivar and in 14 commercial Korean and 14 processed potato
      foods sold in the United States (chips, snacks, mashed potatoes, fries). The AA
      content for the four cultivars ranged from 16 to 46 mg/100 g of fresh weight. The
      distribution of AA in each of the eight potato slices (sticks, plugs) cut
      horizontally from the stem end of the Dejima potato ranged from 6.8 to 19.3% of
      the total. The corresponding distribution in seven sticks cut vertically was much
      narrower, ranging from 11.7 to 17.5% of the total. Losses of AA in water (pH 5.2)
      were significantly greater than in 5% metaphosphoric acid (pH 1.0). Less
      degradation occurred in water solutions of the vitamin stored at 1 degree C than
      at 25 degrees C. Losses of AA observed during home-processing of three varieties
      with low (Dejima, 16 mg/100 g), intermediate (Sumi, 32 mg/100 g), and high
      (Chaju, 42 mg/100 g) AA contents were as follows: boiling in water, 77-88%;
      boiling in water containing 1-3% NaCl, 61-79%; frying in oil, 55-79%; sauteing,
      61-67%; pressure-cooking in water, 56-60%; braising, 50-63%; baking, 33-51%; and
      microwaving, 21-33%. The content of the Korean foods ranged from trace amounts to
      25 mg/100 g and that of the U.S. foods from 0.4 to 46 mg/100 g. These results
      permit optimization of the vitamin C content of the diet by (a) using high
      vitamin C potato varieties such as Chaju, (b) selecting sticks cut horizontally
      for frying, (c) baking or microwaving rather than boiling or frying, and (d)
      selecting commercial potato foods with a high vitamin C content.

PMID- 15479017
TI  - Mineral ion content of the seeds of six cultivars of Bahraini date palm (Phoenix
      dactylifera).
AB  - The mineral ion composition of six different cultivars of Bahraini dates palm
      (Phoenix dactylifera) seeds (Khalas, Murzban, Khunaizi, Khawajah, Khasaib Asfor,
      and Khaseeb) were analyzed using flame atomic absorption spectroscopy (AA and
      ICPS). Murzban was found to contain the higher mineral ion content. The essential
      bulk metal ions in the six cultivars were found to be dominant, where [K+] was
      the highest and [Ca2+] was the lowest. The decreasing order of essential trace
      metal ion concentrations is Fe2+ > Mn2+ > Zn2+. Lead ion content was found to be
      higher than cadmium ion as metal ion pollutant. Mineral ion contents of Bahraini
      date palm seeds and those of imported coffee grain and barley were studied,
      because date palm seeds, coffee grain, and barley are used for coffee drinks.

PMID- 15479018
TI  - Influence of variety and storage on the polyphenol composition of apple flesh.
AB  - Apple is among the most consumed fruits worldwide. It is available on the market
      for the whole year being a major source of dietary polyphenols. Several studies
      suggested that apple polyphenols could play a role in prevention of degenarative
      diseases. The action of these compounds has been partially ascribed to their
      antioxidative ability, and fruit antioxidants profile is influenced by apple
      variety and by the postharvest storage. In this work, the polyphenols composition
      of the flesh of four apple varieties cultivated in southern Italy were
      investigated by HPLC, and a flow injection MS/MS procedure to quantify
      cholorogenic acid and catechins was set up. Phenolic composition and the radical
      scavenging activity were monitored during a postharvest storage of four months.
      The quantification by flow injection procedure gives results comparable to those
      obtained by HPLC, and the increase of the antioxidant activity during storage
      correlated with an increase of the concentration of catechin and phloridzin. This
      trend is particularly evident for the variety "Annurca" which is a typical
      product cultivated in the area around Naples. The genetic characteristics of the
      Annurca variety together with the anticipated harvest time and the peculiar
      postharvest conditions are likely responsible for this increase of the
      antioxidant activity.

PMID- 15479019
TI  - Quantitation of polyphenols in different apple varieties.
AB  - Forty-one apple samples, representing eight of the most widely cultivated
      varieties in western Europe, were collected in Trentino, Italy. Samples were
      extracted from fresh fruit with a mixture of acetone/water to achieve a good
      extraction of polyphenols, including proanthocyanidin oligomers which were
      analyzed by normal-phase HPLC. Up to 20 compounds including catechin,
      epicatechin, B2 procyanidin, hydroxycinnamates, flavonols, anthocyanins, and
      dihydrochalcones were analyzed by reversed-phase HPLC and LC-MS. Total polyphenol
      content was independently measured with an optimized Folin-Ciocalteu assay. The
      mean content of total polyphenols lay between 66.2 and 211.9 mg/100 g of FW
      depending on the variety. With chromatographic analysis, it was possible to
      explain the whole amount of total polyphenols measured by the FC assay. Flavanols
      (catechin and proanthocyanidins) are the major class of apple polyphenols (71
      90%), followed by hydroxycinnamates (4-18%), flavonols (1-11%), dihydrochalcones
      (2-6%), and in red apples anthocyanins (1-3%).

PMID- 15479020
TI  - Development of pyrethroid substrates for esterases associated with pyrethroid
      resistance in the tobacco budworm, Heliothis virescens (F.).
AB  - Assays to detect esterases associated with resistance to organophosphorus and
      pyrethroid insecticides in larvae of H. virescens were developed and evaluated.
      Cross-resistance to a variety of insecticides was measured in strains resulting
      from selection with either profenofos (OP-R) or cypermethrin (PYR-R), and
      resistance in both strains appeared to have a metabolic component. Esters were
      synthesized that coupled 3-(2,2-dichlorovinyl)-2,2
      dimethylcyclopropanecarboxylate, the acid moiety of some pyrethroid insecticides,
      with groups (e.g., p-nitrophenyl-) that could be detected spectrophotometrically
      following hydrolysis of the resulting esters. Activities toward these pyrethroid
      esters were significantly higher in both resistant strains than those in a
      susceptible reference strain. In addition, all pyrethroid esters significantly
      increased the toxicity of cypermethrin in bioassays with larvae from both PYR-R
      and OP-R strains. The biological and biochemical activities of these compounds
      are compared with those with more conventional esterase substrates and
      insecticide synergists, and the utility of pyrethroid esters as components of
      rapid assays for detecting esterases associated with insecticide resistance is
      discussed.

PMID- 15479021
TI  - Interactions of calcium ions with weakly acidic active ingredients slow cuticular
      penetration: a case study with glyphosate.
AB  - Potassium and calcium salts of glyphosate were obtained by titrating glyphosate
      acid with the respective bases to pH 4.0, and rates of penetration of these salts
      across isolated astomatous cuticular membranes (CMs) were measured at 20 degrees
      C and 70, 80, 90, and 100% humidity. K-glyphosate exhibited first-order
      penetration kinetics, and rate constants (k) increased with increasing humidity.
      Ca-glyphosate penetrated only when the humidity above the salt residue was 100%.
      At 90% humidity and below, Ca-glyphosate formed a solid residue on the CMs and
      penetration was not measurable. With Ca-glyphosate, the k value at 100% humidity
      decreased with time and the initial rates were lower than for K-glyphosate by a
      factor of 3.68. After equimolar concentrations of ammonium oxalate were added to
      Ca-glyphosate, high penetration rates close to those measured with K-glyphosate
      were measured at all humidities. Adding ammonium sulfate or potassium carbonate
      also increased rates between 70 and 100% humidity, but they were not as high as
      with ammonium oxalate. The data indicate that at pH 4.0 one Ca2+ ion is bound to
      two glyphosate anions. This salt has its deliquescence point near 100% humidity.
      Therefore, it is a solid at lower humidity and does not penetrate. Its molecular
      weight is 1.82 times larger than that of K-glyphosate, and this greatly slows
      down rates of penetration, even at 100% humidity. The additives tested have low
      solubility products and form insoluble precipitates with Ca2+ ions, but only
      ammonium oxalate binds Ca2+ quantitatively. The resulting ammonium salt of
      glyphosate penetrates at 70-100% humidity and at rates comparable to K
      glyphosate. The results contribute to a better understanding of the hard water
      antagonism observed with glyphosate. It is argued that other pesticides and
      hormones with carboxyl functions are likely to respond to Ca2+ ions in a similar
      fashion. In all of these cases, ammonium oxalate is expected to overcome hard
      water antagonism.

PMID- 15479022
TI  - Solvent extraction characterization of bioavailability of atrazine residues in
      soils.
AB  - Characterization of pesticide bioavailability, particularly in aged soils, is of
      continued interest because this information is necessary for environmental risk
      assessment. The objective of this study was to correlate atrazine residue
      bioavailability in aged soils, as determined by solvent extraction methods, to
      atrazine mineralization by an atrazine-degrading bacterium. Webster clay loam and
      Zimmerman fine sand soils were treated with UL-ring-labeled [14C]atrazine and
      incubated for up to 8 weeks. At the end of each incubation period, soils were
      either not extracted, extracted with 0.01 M CaCl2, or extracted with 0.01 M
      CaCl2/aqueous methanol. Soils were then inoculated with the bacterium Pseudomonas
      sp. strain ADP, which is capable of rapidly mineralizing the atrazine ring. This
      allowed for the evaluation of the bioavailability of aged atrazine residues
      without the contribution of atrazine desorption from soil. Results of these
      studies indicated that the amounts of atrazine residues in aged soils extracted
      by 0.01 M CaCl2 and aqueous methanol were correlated to amounts of atrazine
      mineralized by Pseudomonas sp. strain ADP. Consequently, 0.01 M CaCl2/methanol
      extractable atrazine in aged soils may be used to estimate bioavailable residues,
      and this technique may be useful to determine the bioavailability of other
      compounds in soils, especially other triazine herbicides.

PMID- 15479023
TI  - Odor-active headspace components in fermented red rice in the presence of a
      monascus species.
AB  - Headspace components from rice and agar with (experimental) and without (control)
      inoculation with a Monascus spp. were investigated. Kinetics studies were carried
      out. Using rice as a substrate, 10 and 19 compounds were found for the control
      and the experimental groups, respectively, at day 14. Experimental group
      compounds were composed mainly of alcohols, ketones, and esters, whereas control
      group compounds were composed of aldehydes and ketones. With agar as a substrate,
      only five and three components were found in the control and experimental groups,
      respectively. Five alcohols, four esters, two ketones, and one furan with odor
      activity values (OAV) >1 dominated the overall flavor of the product. With liquid
      inoculation, the first six components with high OAVs were in the following order:
      3-methyl-1-butanol (17) > ethanol (14) > ethyl acetate (10) > 2-methyl-1-propanol
      (15) > ethyl butanoate (11) > 3-methylbutyl acetate (13). Kinetic studies showed
      that most compounds reached their maximum concentrations at 10-12 days. Many
      compounds identified in the model red rice were reported in commercial red sufus,
      and several appeared to contribute solely by red rice.

PMID- 15479024
TI  - New device to simulate swallowing and in vivo aroma release in the throat from
      liquid and semiliquid food systems.
AB  - This paper describes a novel device to simulate in vivo aroma release from
      liquids. This artificial throat simulates the act of swallowing followed by
      exhalation and shows aroma release curves that are similar in shape to in vivo
      release profiles. Liquids are poured down a tube, and a thin liquid film remains
      at the inner wall of the tube. Subsequently, aroma compounds release from this
      film into a stream of air flowing through this tube, which is analyzed by MS-Nose
      analysis. The effects of air flow rate, contact time with glass surface, presence
      of saliva, and addition of whey protein, as well as volume, concentration,
      temperature, and viscosity of the liquid have been studied and compared with
      aroma release measurements in vivo. A high level of agreement was found. These
      results confirm the importance of swallowing for aroma release of liquids, as
      mentioned in the literature, and the usefulness of the new mimicking device.

PMID- 15479025
TI  - Effect of emulsion properties on release of esters under static headspace, in
      vivo, and artificial throat conditions in relation to sensory intensity.
AB  - The effects of oil content and droplet size distributions of dilute oil-in-water
      emulsions on release of four esters with different hydrophobicities were studied
      under in vivo, static headspace, and artificial throat conditions. The effect of
      oil content on orthonasal and retronasal perceived intensity of ethyl hexanoate
      was studied using a seven-person panel. With increasing oil content and with a
      higher hydrophobicity of the aroma compound, a stronger decrease in aroma release
      was found. This effect was stronger under static headspace conditions than under
      in vivo and artificial throat conditions, and the sensory intensity of ethyl
      hexanoate was perceived stronger orthonasally than retronasally. The lowest
      effective oil content was determined for all systems. Of the compounds tested,
      droplet size distribution only influenced the in vivo release of geranyl acetate.
      The artificial throat results correlated well with in vivo release, giving
      support to the assumption that a thin layer of liquid remaining in the throat
      after swallowing determines aroma release.

PMID- 15479026
TI  - Valorization of Brazilian vetiver (Vetiveria zizanioides (L.) Nash ex Small) oil.
AB  - The valorization of extracts from Brazilian vetiver (Vetiveria zizanioides (L.)
      Nash ex Small) roots was studied. This study took into account the extraction
      method, the chemical composition of the extracts, their sensorial
      characteristics, and the possibility of chemical transformations of the product.
      The performed extraction methods were hydrodistillation and extraction with
      supercritical carbon dioxide. Some pretreatment methods were tested on the
      vetiver roots and evaluated in terms of extraction yield, process time, chemical
      composition, and sensorial properties. Supercritical carbon dioxide extraction
      resulted in high yield (3.2%) in significantly less time than the other methods.
      The chemical compositions of the extracts obtained by the different methods were
      also compared to those of commercial vetiver oils from other sources, showing
      that Brazilian samples had a greater acid amount. An extraction in basic medium
      from Brazilian vetiver oil was done to remove its main acid (zizanoic acid),
      which was chemically transformed into an alcohol (khusimol) of desirable
      sensorial properties. Sensory evaluation indicated that the Brazilian volatile
      oil without acid could be used in perfumery and the extract obtained with
      supercritical carbon dioxide could have application in food.

PMID- 15479027
TI  - Antimicrobial and physicochemical properties of chitosan-HPMC-based films.
AB  - To prepare composite films from biopolymers with anti-listerial activity and
      moisture barrier properties, the antimicrobial efficiency of chitosan-hydroxy
      propyl methyl cellulose (HPMC) films, chitosan-HPMC films associated with lipid,
      and chitosan-HPMC films chemically modified by cross-linking were evaluated. In
      addition, the physicochemical properties of composite films were evaluated to
      determine their potential for food applications. The incorporation of stearic
      acid into the composite chitosan-HPMC film formulation decreased water
      sensitivity such as initial solubility in water and water drop angle. Thus, cross
      linking of composite chitosan-HPMC, using citric acid as the cross-linking agent,
      led to a 40% reduction in solubility in water. The water vapor transfer rate of
      HPMC film, approximately 270 g x m(-2) x day(-1) x atm(-1), was improved by
      incorporating chitosan and was further reduced 40% by the addition of stearic
      acid and/or cross-linking. Anti-listerial activity of films was determined on
      solid medium by a numeration technique. Chitosan-HPMC-based films, with and
      without stearic acid, inhibited the growth of Listeria monocytogenes completely.
      On the other hand, a loss of antimicrobial activity after chemical cross-linking
      modification was observed. FTIR and 13C NMR analyses were then conducted in order
      to study a potential chemical modification of biopolymers such as a chemical
      reaction with the amino group of chitosan. To complete the study, the mechanical
      properties of composite films were determined from tensile strength assays.

PMID- 15479028
TI  - Application of multielement stable isotope ratio analysis to the characterization
      of French, italian, and spanish cheeses.
AB  - The stable isotope ratios (delta13C, delta15N, and delta34S of casein and
      delta13C and delta18O of glycerol) measured by IRMS of French, Italian, and
      Spanish cheeses are presented and discussed. Variability factors such as animal
      feeding regimen, geographical origin, and climatic and seasonal conditions were
      studied to check the possibilities of cheese characterization offered by each
      isotopic parameter. Delta13C values of both casein and glycerol appeared to be
      strongly correlated to the amount of maize in the animal diet. Delta15N and
      delta34S of casein proved to be mostly influenced by the geoclimatic conditions
      of the area (aridity, closeness to the sea, altitude). Delta18O of glycerol was
      more dependent on the geographical origin of the cheeses and on climatic/seasonal
      parameters. By applying a multivariate stepwise canonical discriminant analysis,
      good discrimination possibilities for the different European cheeses were
      obtained, confirmed by the classification analysis, when >90% of the samples were
      correctly reclassified.

PMID- 15479029
TI  - Reactivity of bovine whey proteins, peptides, and amino acids toward triplet
      riboflavin as studied by laser flash photolysis.
AB  - The reaction between the triplet excited state of riboflavin and amino acids,
      peptides, and bovine whey proteins was investigated in aqueous solution in the pH
      range from 4 to 9 at 24 degrees C using nanosecond laser flash photolysis. Only
      tyrosine and tryptophan (and their peptides) were found to compete with oxygen in
      quenching the triplet state of riboflavin in aqueous solution, with second-order
      rate constants close to the diffusion limit, 1.75 x 10(9) and 1.40 x 10(9) L mol(
      1) s(-1) for tyrosine and tryptophan, respectively, with beta-lactoglobulin and
      bovine serum albumin having comparable rate constants of 3.62 x 10(8) and 2.25 x
      10(8) L mol(-1) s(-1), respectively. Tyrosine, tryptophan, and their peptides
      react with the photoexcited triplet state of riboflavin by electron transfer from
      the tyrosine and tryptophan moieties followed by a fast protonation of the
      resulting riboflavin anion rather than by direct H-atom abstraction, which could
      be monitored by time-resolved transient absorption spectroscopy as a decay of
      triplet riboflavin followed by a rise in riboflavin anion radical absorption. For
      cysteine- and thiol-containing peptides, second-order rate constants depend
      strongly on pH, for cysteine corresponding to pKaRSH = 8.35. H-atom abstraction
      seems to operate at low pH, which with rising pH gradually is replaced by
      electron transfer from the thiol anion. From the pH dependence of the second
      order rate constant, the respective values for the H-atom abstraction (k = 1.64 x
      10(6) L mol(-1) s(-1)) and for the electron transfer (k = 1.20 x 10(9) L mol(-1)
      s(-1)) were determined.

PMID- 15479030
TI  - Effect of diet on the deposition of n-3 fatty acids, conjugated linoleic and
      C18:1trans fatty acid isomers in muscle lipids of German Holstein bulls.
AB  - This study examined the effects of feeding diets rich in either n-3 or n-6
      polyunsaturated fatty acids (PUFA) on the fatty acid composition of longissimus
      muscle in beef bulls. Thirty-three German Holstein bulls were randomly allocated
      to either an indoor concentrate system or periods of pasture feeding (160 days)
      followed by a finishing period on a concentrate containing linseed to enhance the
      contents of n-3 PUFA and conjugated linoleic acids (CLA) in beef muscle. The
      relative proportion and concentration (mg/100 g fresh muscle) of n-3 fatty acids
      in the phospholipid and triglyceride fractions were significantly increased (p <
      or = 0.05) in muscle lipids of pasture-fed bulls. The pasture feeding affected
      the distribution of individual CLA isomers in the muscle lipids. The proportion
      of the most prominent isomer, CLA cis-9,trans-11, was decreased from 73.5 to
      65.0% of total CLA in bulls fed on concentrate as compared to pasture. The second
      most abundant CLA isomers were CLA trans-7,cis-9 and CLA trans-11,cis-13 in bulls
      fed on concentrate and pasture, respectively. Diet had no effect on the
      concentration of C18:1 trans-11. In contrast, the concentration of the C18:1
      trans-13/14, trans-15, and trans-16 isomers in the muscle lipids was up to two
      times higher in pasture-fed as compared to concentrate-fed bulls. Pasture feeding
      enhanced the concentration of n-3 fatty acids, but the diet had no effect on the
      concentration of CLA cis-9,trans-11.

PMID- 15479031
TI  - Purification and identification of water-soluble phosphopeptides from cheese
      using Fe(III) affinity chromatography and mass spectrometry.
AB  - Water-soluble phosphopeptides from cheese were isolated using immobilized metal
      affinity chromatography (IMAC). Phosphopeptides from aqueous cheese extracts were
      completely retained on iminodiacetic acid (IDA) Sepharose equilibrated with FeCl3
      and subsequently eluted with ammonium dihydrogen phosphate. Peptides in the
      eluate from the IMAC-Fe(III) column were identified using reversed phase liquid
      chromatography-electronic spray identification-tandem mass spectrometry.
      Phosphopeptides from two different cheeses were analyzed using the described
      method: a 10-month-old semihard Herrgard cheese made with mesophilic starter and
      a 24-month-old Parmigiano Reggiano cheese made with thermophilic starter. Elution
      of the IMAC-Fe(III) column with a gradient of ammonium dihydrogen phosphate
      resulted in three distinct peaks for Herrgard cheese corresponding to peptides
      carrying one, two, and four phosphorylated serine residues, respectively. Sixty
      five different phosphopeptides were identified from the Herrgard, whereas only 9
      from the Parmigiano Reggiano.

PMID- 15479032
TI  - Inhibition of extrahepatic human cytochromes P450 1A1 and 1B1 by metabolism of
      isoflavones found in Trifolium pratense (red clover).
AB  - Biochanin A and formononetin are the predominant isoflavones in red clover. In a
      previous study (J. Agric. Food Chem. 2002, 50, 4783-4790), it was demonstrated
      that human liver microsomes converted biochanin A and formononetin to genistein
      and daidzein. This paper now shows CYP1B1-catalyzed O-demethylation of biochanin
      A and formononetin to produce genistein and daidzein, respectively, which inhibit
      CYP1B1. Recombinant human CYP1A1 or CYP1B1 was incubated with biochanin A or
      formononetin. CYP1A1 catalyzed isoflavone 4'-O-demethylation and hydroxylations
      with similar efficiency, whereas CYP1B1 favored 4'-O-demethylation over
      hydroxylations. Three of the biochanin A metabolites (5,7,3'-trihydroxy-4'
      methoxyisoflavone, 5,7,8-trihydroxy-4'-methoxyisoflavone, and 5,6,7-trihydroxy-4'
      methoxyisoflavone) were characterized by 1H NMR spectroscopy and mass
      spectrometry. Daidzein (Ki = 3.7 microM) exhibited competitive inhibition of
      CYP1B1 7-ethoxyresorufin O-deethylase activity, and genistein (Ki = 1.9 microM)
      exhibited mixed inhibition. Biochanin A and/or formononetin may exert
      anticarcinogenic effects directly by acting as competitive substrates for CYP1B1
      or indirectly through their metabolites daidzein and genistein, which inhibit
      CYP1B1.

PMID- 15479033
TI  - Horseradish peroxidase-catalyzed cross-linking of feruloylated arabinoxylans with
      beta-casein.
AB  - Heterologous conjugates of wheat arabinoxylan and beta-casein were prepared via
      enzymatic cross-linking, using sequential addition of the arabinoxylan to a
      mixture of beta-casein, peroxidase, and hydrogen peroxide. The maximal formation
      of adducts between the beta-casein and the feruloylated arabinoxylan was reached
      at a protein-to-arabinoxylan ratio of 10:1, in combination with a molar ratio
      hydrogen peroxide to substrate of 2:1 and a molar protein-to-enzyme ratio between
      10(2) and 10(4). The protein-arabinoxylan adducts were separated from the
      arabinoxylan homopolymers by size exclusion and anion exchange chromatography.
      The molar ratio protein:arabinoxylan in the purified conjugates varied between
      0.1 and 5.6. This is the first report on the large-scale enzymatic preparation of
      heterologous protein-arabinoxylan conjugates.

PMID- 15479034
TI  - Sensory and analytical study of rose sparkling wines manufactured by second
      fermentation in the bottle.
AB  - The sensory and analytical characteristics of five rose sparkling wines
      manufactured by the traditional method have been determined. Moreover, the
      changes that take place in the nitrogen and volatile fraction of the wines during
      the second fermentation and the aging with the yeasts have been studied. Each of
      these wines was made from a single industrial rose base wine of the Garnacha
      Tinta variety, with five selected yeasts strains. The base wine had a low content
      in free amino acids, 16 mg/L, and the yeast consumed more peptides than free
      amino acids during second fermentation. From the application of the two-way
      analysis of variance, yeast strain, and aging time factors to the data of
      volatile compounds, it has been found that most of the differences between these
      sparkling wines are due to the aging time. It has been verified that these rose
      sparkling wines have foam of good quality and that the grape variety Garnacha
      Tinta is suitable for the production of rose sparkling wines.

PMID- 15479035
TI  - Novel antioxidant peptides from fermented mushroom Ganoderma lucidum.
AB  - Oxidative stress has been linked with the pathogenesis of many human diseases
      including cancer, aging, and atherosclerosis. The present study investigates the
      antioxidant activities of peptides isolated from the medicinal mushroom,
      Ganoderma lucidum. G. lucidum has been shown to possess potent antioxidant
      activity with little or no side effects. Polysaccharide, polysaccharide-peptide
      complex, and phenolic components of G. lucidum have been proposed to be
      responsible for this antioxidant effect. However, research has shown that the G.
      lucidum peptide (GLP) is the major antioxidant component of G. lucidum. The
      objective of this study was to evaluate the antioxidant activity of this peptide
      using different oxidation systems. GLP showed potent antioxidant activities in
      both lightproof soybean oil and lard systems, assessed by lipid peroxidant value.
      Compared to butylated hydroxytoluene, GLP showed a higher antioxidant activity in
      the soybean oil system. Soybean lipoxygenase activity was blocked by GLP in a
      dose-dependent manner with an IC50 value of 27.1 microg/mL. GLP showed scavenging
      activity toward hydroxyl radicals produced in a deoxyribose system with an IC50
      value of 25 microg/mL, and GLP effectively quenched superoxide radical anion
      produced by pyrogallol autoxidation in a dose-dependent manner. Malondialdehyde
      level has been used as the oxidation index in many biological systems. GLP showed
      substantial antioxidant activity in the rat liver tissue homogenates and
      mitochondrial membrane peroxidation systems. The auto-hemolysis of rat red blood
      cells was also blocked by GLP in a dose-dependent manner. On the basis of these
      results, it is concluded that GLP is the major constituent responsible for the
      antioxidant activity of G. lucidum. GLP could play an important role in the
      inhibition of lipid peroxidation in biological systems through its antioxidant,
      metal chelating, and free radical scavenging activities.

PMID- 15479036
TI  - Identification and quantification of the conjugated metabolites derived from
      orally administered hesperidin in rat plasma.
AB  - Hesperidin is a biologically effective flavonoid. Several studies have reported
      that dietary hesperidin was converted to conjugated metabolites, such as
      hesperetin-glucuronides and sulfoglucuronides, during absorption and metabolism.
      However, the chemical structures of the conjugated metabolites, especially the
      sites of glucuronidation and sulfoglucuronidation in plasma, were unconfirmed.
      Therefore, the concentrations of the metabolites conjugated at various sites in
      plasma could not be individually quantified. In the present study, we identified
      the chemical structures and concentrations of the major conjugated metabolites in
      rat plasma after oral administration of hesperidin. Two hesperetin-glucuronides
      were prepared and identified as hesperetin-7-O-beta-D-glucuronide and hesperetin
      3'-O-beta-D-glucuronide. Using these authentic compounds, the concentrations of
      hesperetin-7-O-beta-D-glucuronide and hesperetin-3'-O-beta-D-glucuronide in rat
      plasma were individually determined by liquid chromatography-mass spectrometry.
      In rat plasma, hesperetin-glucuronides were primarily comprised of hesperetin-7-O
      beta-D-glucuronide and hesperetin-3'-O-beta-D-glucuronide. The concentration of
      hesperetin-7-O-beta-D-glucuronide was slightly higher than that of hesperetin-3'
      O-beta-D-glucuronide. Furthermore, not only hesperetin conjugates but also
      homoeriodictyol conjugates were observed in rat plasma. The present study is the
      first report elucidating the chemical structures and changes in individual
      concentrations in rat plasma of glucuronides derived from orally administered
      hesperidin.

PMID- 15479037
TI  - Inhibition of aflatoxin biosynthesis in Aspergillus flavus by
      diferuloylputrescine and p-coumaroylferuloylputrescine.
AB  - A mixture of diferuloylputrescine/p-coumaroylferuloylputrescine (85:15, w/w)
      demonstrated inhibitory activity against aflatoxin B1 biosynthesis in Aspergillus
      flavus isolate AF13. Inhibition was concentration dependent, with a 50% effective
      dose of 30 microg of diferuloylputrescine/p-coumaroylferuloylputrescine per
      milliliter of medium. Aflatoxin inhibition levels of up to 93% were achieved
      using this conjugated polyamine material. This diconjugated polyamine mixture did
      not display inhibitory effects on A. flavus growth (mycelial weight) at any of
      the concentrations tested. A survey of hand-dissected corn (Zea mays) kernel
      tissues, including endosperm, germ, pericarp, and wax, revealed that the highest
      concentrations of these conjugated polyamines were localized in the pericarp of
      the seed. Analysis of a number of corn accessions did not reveal a correlation
      between diferuloylputrescine/ p-coumaroylferuloylputrescine concentration and
      resistance/susceptibility to A. flavus infection. The localization of these
      diconjugated polyamine components in the pericarp, which functions as a physical
      barrier and surrounds the internal food storage reserves, suggests a defensive
      role for these materials.

PMID- 15479038
TI  - Solid-phase extraction and LC-MS analysis of pyrrolizidine alkaloids in honeys.
AB  - Strong-cation-exchange, solid-phase extraction of pyrrolizidine alkaloids and
      their N-oxides from honey samples was followed by reduction of the N-oxides and
      subsequent analysis of total pyrrolizidine alkaloids using high-performance
      liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.
      A limited survey of 63 preprocessing samples of honey, purposefully biased toward
      honeys attributed to floral sources known to produce pyrrolizidine alkaloids,
      demonstrated levels of pyrrolizidine alkaloids up to approximately 2000 parts per
      billion (ppb) in a sample attributed to Echium plantagineum. Up to 800 ppb
      pyrrolizidine alkaloids was detected in some honeys not attributed by the
      collector to any pyrrolizidine alkaloid-producing floral source. No pyrrolizidine
      alkaloids were detected in approximately 30% of the samples in this limited
      study, while some honeys showed the copresence of pyrrolizidine alkaloids from
      multiple floral sources such as E. plantagineum and Heliotropium europaeum. In
      addition, retail samples of blended honeys (with no labeling to suggest that
      pyrrolizidine alkaloid-producing floral sources were used in the blends) have
      been shown to contain up to approximately 250 ppb pyrrolizidine alkaloids.

PMID- 15479039
TI  - Investigation of the pathway for inter-copper electron transfer in
      peptidylglycine alpha-amidating monooxygenase.
AB  - Peptidylglycine alpha-amidating monooxygenase catalyzes the oxidative cleavage of
      glycine extended peptides at their terminus. In the course of the reaction, there
      is a requisite long-range electron transfer between the two copper centers (CuH
      and CuM) located in the hydroxylating domain. This communication presents data
      that argue against the participation of the extended peptide backbone of
      substrate in the long-range electron transfer. We propose that electron transfer
      occurs via the bulk solvent that separates CuH from CuM.

PMID- 15479040
TI  - Toward mimicking viral geometry with metal-organic systems.
AB  - Icosahedral and cuboctahedral arrangements of calixarenes, a nanometer-scale,
      spheroidal assembly of 12 calixarene molecules, can be manipulated in a highly
      controlled fashion. Previously, such assemblies were observed to favor placement
      of the calixarenes at the vertexes of an icosahedron. A supramolecular constraint
      is employed in order to enforce molecular alignment and produce a cuboctahedral
      arrangement. The internal volume of the cuboctahedron is approximately 30%
      greater than that of the icosahedron. Furthermore, in stark contrast to that of
      the icosahedral Platonic solid, the shell of the cuboctahedral Archimedean solid
      is porous.

PMID- 15479041
TI  - Spontaneous assembly of organic thiocyanates on gold sufaces. Alternative
      precursors for gold thiolate assemblies.
AB  - Thiolate self-assembly on gold has proven to be a valuable technique for
      assembling monolayers on a wide variety of substrates. However, the oxidative
      instability of the thiols, especially aromatic thiols and alpha,omega-dithiols,
      presents several difficulties. Shown here is that thiocyanates, easily
      synthesized stable thiol derivatives, can be directly assembled on gold surfaces
      with no auxiliary reagents required. Assembly is complete in 24 h and leaves a
      similar gold thiolate structure as seen in typical thiol self-assembled
      monolayers.

PMID- 15479042
TI  - Direct generation of Ti-enolate of alpha-CF3 ketone: theoretical study and high
      yielding and diastereoselective Aldol reaction.
AB  - Success in the direct generation of the Ti-enolate of alpha-CF3 ketone and its
      aldol reaction is reported. The importance of Ti-F interaction during the course
      of the reaction is also reported.

PMID- 15479043
TI  - Electric-field-induced conductance switching in FeCo Prussian blue analogues.
AB  - FeCo Prussian blue analogues, which are known as typical molecule-based magnets,
      exhibited abrupt conductance switching by applying a high electric field as well
      as by varying the temperature. The current density versus electric field (J-E)
      curves of FeCo Prussian blue with Rb cations in interstitial sites shows so
      called negative resistance effects at electric fields higher than the threshold
      voltage. This means that the FeCo Prussian blue analogues are multiproperty
      materials in the sense that their conducting, magnetic, and optical properties
      can be reversibly controlled by certain external stimuli.

PMID- 15479044
TI  - Elucidating reactivity differences in palladium-catalyzed coupling processes: the
      chemistry of palladium hydrides.
AB  - This communication describes a series of studies directed at obtaining a better
      understanding of the Heck reaction. For the first time, the postulated palladium
      hydride intermediate (L2PdHX) in the catalytic cycle of the Heck arylation has
      been identified. In addition, this study establishes that the base-mediated Pd(0)
      regeneration step (L2PdHX --> PdL2) of the cycle can be kinetically slow and
      thermodynamically unfavorable and that the process is remarkably sensitive to the
      structure of L (PCy3 vs P(t-Bu)3). Finally, this investigation demonstrates that,
      for certain catalyst systems, slow rates of Heck arylation can be correlated with
      reluctant reductive elimination of L2PdHX, furnishing a possible rationalization
      for Bronsted-base (Cs2CO3 vs Cy2NMe) and ligand (PCy3 vs P(t-Bu)3) effects that
      have been observed.

PMID- 15479045
TI  - Indirect covariance NMR spectroscopy.
AB  - A novel NMR scheme is presented that establishes homonuclear spin correlations
      without requiring direct detection of the spin species. This covariance NMR
      method is experimentally demonstrated for a mixture of amino acids and for the
      uniformly 13C-labeled cyclic decapeptide antamanide using a 13C-edited TOCSY
      experiment. The method opens up new avenues for the experimental analysis of
      molecules containing insensitive spins encountered in biomolecular NMR and
      analytical chemistry including metabolomics.

PMID- 15479046
TI  - Asymmetric syntheses of phosphatidylinositol-3-phosphates with saturated and
      unsaturated side chains through catalytic asymmetric phosphorylation.
AB  - Highly direct asymmetric syntheses of phosphatidylinositol-3-phosphate (PI3P) in
      each enantiomerically pure form have been achieved. The key step involves
      catalytic asymmetric phosphorylation of meso-myo-inositol derivatives through
      desymmetrization. Protecting group schemes have been employed that allow for
      synthesis of PI3P with either saturated or arachidonate side chains, in analogy
      to the naturally occurring systems. Syntheses in each enantiomeric series are
      reported that rely on the choice of enantioselective peptide-based catalyst to
      define the enantiomeric series in which the syntheses are carried out.

PMID- 15479047
TI  - How fluorous is poly(2,2-bis(trifluoromethyl)-4,5-difluoro-1,3-dioxide-co
      tetrafluoroethylene) (Teflon AF)?
AB  - We investigated poly(2,2-bis(trifluoromethyl)-4,5-difluoro-1,3-dioxide-co
      tetrafluoroethylene (Teflon AF 2400, Tg = 240 degrees C), a stable and permeable
      fluorous polymer, as a transport/extraction medium for solutes for the first
      time. From the study of transport behavior of a series of solutes (in chloroform
      solution) through the film, and detailed measurement of the partitioning and
      diffusion of benzene in the film, we showed that the Teflon AF film is influenced
      by the solvent to which it is exposed. In particular, the solvent chloroform is
      sorbed in the film at a high concentration of 1.13 M. This plasticizes the film,
      so that the diffusion coefficient of benzene is about 3 orders of magnitude
      larger in a chloroform-equilibrated film compared to benzene coming from the gas
      phase into a "dry" film. The partition ratio of the polar solute 3
      hydroxypyridine is dramatically higher in the case of partitioning between
      chloroform and a film (0.02) compared to partitioning between chloroform and the
      fluorous solvent FC-72 (6.7 x 10-5). Krytox FSH, a carboxylic acid terminated
      perfluoropolyether, plasticizes films. Tg in a 50% (w/w) film decreases to -40
      degrees C. This carboxylic acid is capable of molecular recognition in the film.
      The noncovalent association between Krytox FSH (0.13 M in the film) and 3
      hydroxypyridine increases the distribution ratio of the polar solute into the
      film by 41 times. In comparison, the partition ratio into a fluorocarbon solvent
      (FC-72) increases 15 000 times under the same conditions. As a result of imbibing
      organic solvent, the films of Teflon AF 2400 are not as fluorous as a fluorous
      liquid.

PMID- 15479048
TI  - Isothermal titration calorimetry studies on the binding of DNA bases and PNA base
      monomers to gold nanoparticles.
AB  - An isothermal titration calorimetric (ITC) investigation of the interaction of
      DNA bases and PNA base monomers with gold nanoparticles is described revealing a
      binding sequence in the order C > G > A > T. Direct measurement of the strength
      of interaction of ligands with nanogold by ITC has important implications in
      surface modification strategies for biomedical, catalysis, and nanoarchitecture
      applications.

PMID- 15479049
TI  - Surprising bacterial nucleotidyltransferase selectivity in the conversion of
      carbaglucose-1-phosphate.
AB  - The drive to understand the molecular determinants of carbohydrate binding as
      well as the search for more chemically and biochemically stable sugar derivatives
      and carbohydrate-based therapeutics has led to the synthesis of a variety of
      analogues that replace the glycosidic oxygen with sulfur or carbon. In contrast,
      the effect of substitution of the ring oxygen on the conformations and enzymatic
      tolerance of sugars has been largely neglected, in part because of the difficulty
      in obtaining these analogues. Herein we report the first synthesis of the
      carbocyclic version of the most common naturally occurring sugar-1-phosphate,
      glucose-1-phosphate, and its evaluation with bacterial and eukaryotic sugar
      nucleotidyltransferases. In contrast to results with the eukaryotic enzyme, the
      carbaglucose-1-phosphate serves as a substrate for the bacterial enzyme to
      provide the carbocyclic uridinediphosphoglucose. This result demonstrates the
      first chemoenzymatic strategy to this class of glycosyltransferase inhibitors and
      stable activated sugar mimics for cocrystallization with glycosyltransferases and
      their glycosyl acceptors. This difference in turnover between enzymes also
      suggests the possibility of using sugar nucleotidyltransferases in vivo to
      convert prodrug forms of glycosyltransferase inhibitors. In addition, we report
      several microwave-assisted reactions, including a five minute Ferrier
      rearrangement with palladium, that accelerate the synthesis of carbocyclic sugars
      for further studies.

PMID- 15479050
TI  - Radical deoxygenation of hydroxyl groups via phosphites.
AB  - A highly efficient, two-step sequence method for the deoxygenation of hydroxyl
      groups has been developed. The method involves the preparation of the 2-(2
      iodophenyl)ethyl methyl phosphite derivative of an alcohol using methyl
      dichlorophosphite and 2-(2-iodophenyl)ethanol. Treatment of the phosphite
      intermediate with (n-Bu)3SnH/AIBN in refluxing benzene cleanly produces the
      deoxygenation product of the original alcohol.

PMID- 15479051
TI  - Selective addition to iridium of aryl C-H bonds ortho to coordinating groups. Not
      chelation-assisted.
AB  - Precursors of the pincer-ligated iridium species, (PCP)Ir, react with
      nitrobenzene or acetophenone at ambient temperature to give O,C-chelated
      complexes resulting from addition of an aryl C-H bond and coordination of a nitro
      or acetyl oxygen. The C-H additions appear to be completely regioselective for
      the position ortho to the functional group; however, structural characterization
      and low-temperature NMR studies demonstrate that the reaction does not proceed
      via coordination of the functional group followed by C-H addition. In the case of
      nitrobenzene, kinetic preference for the para and meta positions is demonstrated
      at low temperature. Addition occurs more slowly at the ortho position, without
      assistance by the functional group; the ortho-C-H addition product is then
      trapped by chelation.

PMID- 15479052
TI  - Exploiting the right side of the Ramachandran plot: substitution of glycines by D
      alanine can significantly increase protein stability.
AB  - A major goal of protein engineering is the enhancement of protein stability. Here
      we demonstrate a rational method for enhancing the stability of globular proteins
      by targeting glycine residues which adopt conformations with Phi > 0. Replacement
      of such a glycine by d-alanine can lead to a significant increase in stability.
      The approach is tested at three sites in two model proteins. NMR and CD indicated
      that the substitutions do not alter the structure. Replacement of glycine-24 of
      the N-terminal domain of L9 (NTL9) with d-Ala results in an increase in stability
      of 1.3 kcal mol-1, while replacement of glycine-34 of NTL9 leads to an increase
      of 1.9 kcal mol-1. Replacement of glycine-331 of the UBA domain with d-Ala leads
      to an increase in stability of 0.6 kcal mol-1.

PMID- 15479053
TI  - Aminoboranes as "compatible" iminium ion generators in aminative C-C bond
      formations.
AB  - Aminoboranes have been shown to be highly efficient and mild iminium ion
      generators in the Mannich-type aminative coupling of aldehydes with silyl ketene
      acetals. By using aminoboranes bearing bulky amino groups, such as a
      diisopropylamino group, free secondary amines can be successfully used as the
      amino component in a three-component Mannich reaction with aldehydes and silyl
      ketene acetals.

PMID- 15479054
TI  - Catalytic, highly enantio- and diastereoselective pinacol coupling reaction with
      a new tethered bis(8-quinolinolato) ligand.
AB  - A new class of chiral ligand, tethered bis(8-quinolinol) (TBOxH), is developed.
      Its chromium complex, TBOxCrCl (3 mol %), effectively catalyzes the pinacol
      coupling reaction of aromatic aldehydes at room temperature with high yield (up
      to 94%), high diastereoselectivity (up to dl:meso = 98:2), and high
      enantioselectivity (up to 98%). The scope of the present method turns out not to
      be limited to aromatic aldehyde derivatives, as cyclohexanecarboxaldehyde
      undergoes pinacolization as well (44% yield, dl:meso = 93:7, 84% ee). The method
      provides an efficient access to enantioenriched 1,2-diols.

PMID- 15479055
TI  - Controlled synthesis of monodisperse silver nanocubes in water.
AB  - Monodisperse silver nanocubes with edge length of 55 +/- 5 nm were, for the first
      time, synthesized in water on the basis of HTAB-modified silver mirror reaction
      at 120 degrees C (HTAB, n-hexadecyltrimethylammonium bromide). The individual
      nanocube was crystallographically well defined with a single crystal bonded by
      six {200} facets. The nanocubes were soluble to form stable aqueous solutions and
      had a strong tendency to assemble into two-dimensional arrays with regular
      checked pattern on substrate.

PMID- 15479056
TI  - Ferromagnetism in one-dimensional vanadium-benzene sandwich clusters.
AB  - A molecular beam of multilayer vanadium-benzene organometallic complexes
      Vn(C6H6)m was produced by a laser vaporization synthesis method. The magnetic
      moments of the complexes were measured by a molecular beam magnetic deflection
      technique, and were found to increase with the number of vanadium atoms in the
      cluster, showing that the unpaired electrons, which occupy the nonbonding dsigma
      orbitals localized on the metal atoms, couple ferromagnetically. These sandwich
      species represent a new class of one-dimensional molecular magnets in which the
      transition metal atoms are formally zerovalent.

PMID- 15479057
TI  - Fluorescence emission from dendrimers and its pH dependence.
AB  - A strong fluorescence emission was observed from different kinds of dendrimers
      under acidic condition. There was a remarkable difference in fluorescence
      properties between second and fourth generation NH2-terminated poly(amido amine)
      dendrimers. It can be assumed that the backbone of the dendrimer played the key
      role in forming the novel fluorescent center.

PMID- 15479058
TI  - Two-prong inhibitors for human carbonic anhydrase II.
AB  - The enzyme inhibitors are usually designed by taking into consideration the
      overall dimensions of the enzyme's active site pockets. This conventional
      approach often fails to produce desirable affinities of inhibitors for their
      cognate enzymes. To circumvent such constraints, we contemplated enhancing the
      binding affinities of inhibitors by attaching tether groups, which would interact
      with the surface exposed amino acid residues. This strategy has been tested for
      the inhibition of human carbonic anhydrase II. Benzenesulfonamide serves as a
      weak inhibitor for the enzyme, but when it is conjugated to iminodiacetate-Cu2+
      (which interacts with the surface-exposed His residues) via a spacer group, its
      binding affinity is enhanced by about 2 orders of magnitude. This "two-prong"
      approach is expected to serve as a general strategy for converting weak
      inhibitors of enzymes into tight-binding inhibitors.

PMID- 15479059
TI  - Control of a multisubunit DNA motor by a thermoresponsive polymer switch.
AB  - The conjugation of thermoresponsive polymers to multisubunit, multifunctional
      hybrid type 1 DNA restriction-modification (R-M) enzymes enables temperature
      controlled "switching" of DNA methylation by the conjugate. Polymers attached to
      the enzyme at a subunit distal to the methylation subunit allow retention of DNA
      recognition and ATPase activity while controlling methylation of plasmid DNA.
      This regulation of enzyme activity arises from the coil-globule phase transitions
      of the polymer as shown in light scattering and gel retardation assays.

PMID- 15479060
TI  - Equilibrium characteristic at ordered-disordered phase boundary in centrifuged
      nonequilibrium colloidal-crystal system.
AB  - We show that a crystalline-noncrystalline boundary that temporarily appeared in a
      sediment centrifuged from a relatively dilute colloidal suspension can be
      regarded to be at a phase equilibrium. On the basis of this, we can determine the
      critical particle concentration for colloidal crystallization using an extremely
      small amount of specimen by spatially resolved spectroscopy.

PMID- 15479061
TI  - Nanopore formation by self-assembly of the model genetically engineered elastin
      like polymer [(VPGVG)2(VPGEG)(VPGVG)2]15.
AB  - The self-assembly characteristics of the model genetically engineered elastin
      like polymer [(VPGVG)2(VPGEG)(VPGVG)2]15 have been studied in this work. An AFM
      study of the topology of polymer films deposited from acid and basic solutions on
      a hydrophobic silicon substrate has been carried out. Under acidic conditions,
      polymer deposition results in a flat surface with no particular topological
      features. However, from basic solutions, polymer deposition clearly shows an
      aperiodic pattern of nanopores ( approximately 70 nm width and separated about
      150 nm). This dramatic dependence of film topology on pH is explained in terms of
      the different polarity of the free gamma-carboxyl group of the glutamic acid. In
      the carboxylate form, this moiety shows a markedly higher polarity than the rest
      of the polymer domains and the substrate itself. Under these conditions, the
      charged carboxylates impede hydrophobic contact with their surroundings, which is
      the predominant assembly pathway for this type of polymer. The charged domains,
      along with their hydration sphere, are then segregated from the hydrophobic
      surroundings giving rise to nanopores.

PMID- 15479062
TI  - Dihydrogen activation by a diruthenium analogue of the Fe-only hydrogenase active
      site.
AB  - The photochemical reaction of Ru2(S2C3H6)(CO)4(PCy3)2 (1) and H2 gives the
      dihydride Ru2(S2C3H6)(mu-H)(H)(CO)3(PCy3)2 (2). NMR and crystallographic studies
      reveal mutually trans basal phosphine ligands and both bridging and terminal
      hydrides. Ru2(S2C2H4)(CO)4(PCy3)2 behaves similarly. Other HX substrates undergo
      photoaddition to 1, affording Ru2(S2C3H6)(mu-H)(X)(CO)3(PCy3)2 for X = OTs (3a),
      Cl (3b), and SPh (3c). Treatment of Ru2(S2C3H6)(mu-H)(H)(CO)3(PCy3)2 with
      [H(OEt2)]BArF4 (ArF = B(C6H3-3,5-(CF3)2) in CD2Cl2 gives [Ru2(S2C3H6)(mu
      H)(CO)3(PCy3)2(H2)]+ (4), which catalyzes H2-D2 exchange. The reaction of 2 with
      [D(OEt2)]BArF4 gave [Ru2(S2C3H6)(mu-H)(CO)3(PCy3)2(HD)]+ (JH-D = 31 Hz). These
      studies provide the first models for the Fe-only hydrogenases that bear
      dihydrogen and terminal hydrido ligands.

PMID- 15479063
TI  - A polyamidoamine dendrimer-capped mesoporous silica nanosphere-based gene
      transfection reagent.
AB  - We synthesized a MCM-41-type mesoporous silica nanosphere (MSN)-based gene
      transfection system, where second generation (G2) polyamidoamines (PAMAMs) were
      covalently attached to the surface of MSN. The G2-PAMAM-capped MSN material (G2
      MSN) was used to complex with a plasmid DNA (pEGFP-C1) that encodes for an
      enhanced green fluorescence protein. The gene transfection efficacy, uptake
      mechanism, and biocompatibility of the G2-MSN system with various cell types,
      such as neural glia (astrocytes), human cervical cancer (HeLa), and Chinese
      hamster ovarian (CHO) cells, were investigated. The mesoporous structure of the
      MSN material allows membrane-impermeable molecules, such as pharmaceutical drugs
      and fluorescent dyes, to be encapsulated inside the MSN channels. The system
      renders the possibility to serve as a universal transmembrane carrier for
      intracellular drug delivery and imaging applications.

PMID- 15479064
TI  - A new route to supramolecular isomers via molecular templating: nanosized
      molecular polygons of copper(I) 2-methylimidazolates.
AB  - A new facile synthetic strategy successfully leads to the isolation of two
      polygons of high numbers of sides constructed by simple, bent imidazolate
      bridging ligands and two-coordinate CuI ions upon templating of circular organic
      molecules, which were characterized by crystallography.

PMID- 15479065
TI  - Alpha-aldehyde terminally functional methacrylic polymers from living radical
      polymerization: application in protein conjugation "pegylation".
AB  - Application of proteins and peptides as human therapeutics is expanding rapidly
      as drug discovery becomes more prevalent. Conjugation of polymers to proteins can
      circumvent many problems and pegylation of proteins is now emerging as acceptable
      practice. This paper describes the synthesis of alpha-aldehyde-terminated
      poly(methoxyPEG)methacrylates from Cu(I) mediated living radical polymerization
      (Mn = 11 000, 22 000 and 32 000; PDi < 1.15), and their efficient conjugation to
      lysozyme, as a model protein. This offers an attractive and flexible alternative
      to linear poly(ethylene glycol) opening up the possibility of using the full
      power of living radical polymerization.

PMID- 15479066
TI  - Electronic structure of the water-oxidation catalyst
      [(bpy)2(OHx)RuORu(OHy)(bpy)2]z+: weak coupling between the metal centers is
      preferred over strong coupling.
AB  - High-level DFT calculations indicate that the singlet ground state of the water
      oxidizing blue Ru dimer [(bpy)2(OH2)RuIIIORuIII(OH2)(bpy)2]4+ is not due to a
      strong coupling of the excess electrons from each of the low-spin d5 RuIII
      centers across the Ru-O-Ru moiety, as has been assumed to date. Instead, broken
      symmetry orbital calculations suggest that a weak antiferromagnetically (AF)
      coupled singlet state is energetically more favorable by 10-35 kcal/mol.
      Experimentally observed redox potentials can only be reproduced if
      antiferromagnetic coupling is invoked.

PMID- 15479067
TI  - FTIR spectroscopy of buried interfaces in molecular junctions.
AB  - We demonstrate that ATR-FTIR spectroscopy can be used to record high-quality
      vibrational spectra of molecules at buried interfaces in metal-molecule-silicon
      and metal-molecule-metal junctions. This provides quantitative information on the
      structure and conformation of molecules at buried interfaces, an issue of
      critical importance to molecular electronics. In the model systems of Au on
      octadecyltrichlorosilane self-assembled monolayer on Si or mecaptohexadecanoic
      acid multilayers on Au-covered Si, ATR-FTIR suggests that metal deposition leads
      to not only conformational disorder within the film but also the direct
      interaction of metal atoms/clusters with alkyl backbones.

PMID- 15479069
TI  - Formation of giant solvation shells around fulleride anions in liquid ammonia.
AB  - Here, we measure the solvation structure of fulleride C605- anions in potassium
      ammonia solution using neutron diffraction. We find a very strong solvation
      structure consisting of two shells of ammonia densely packed around the anion.
      The system's structure is driven by the propensity of ammonia molecules to direct
      one of their hydrogen bonds to the center of the anion while retaining axial
      hydrogen bonding within the shells. This permits high concentrations of solvent
      separated fulleride anions.

PMID- 15479068
TI  - Raman imaging of PLGA microsphere degradation inside macrophages.
AB  - Understanding the degradation behavior of polymeric microspheres is crucial for
      the successful application of such devices in controlled drug delivery. The
      degradation mechanism of poly(lactic-co-glycolic acid) (PLGA) microspheres inside
      phagocytic cells is not known, but different models for degradation in aqueous
      solution have been proposed. We have used confocal Raman spectroscopy and imaging
      to study the intracellular degradation of PLGA microspheres inside individual
      macrophages. Our results show that ingested microspheres degrade in a
      heterogeneous manner, with a more rapid degradation in the center. Comparison of
      Raman spectra from degrading beads with those of uningested beads reveals that
      ester hydrolysis occurs throughout the phagocytosed microspheres, with a
      selective loss of glycolic acid units. Furthermore, we show that PLGA degradation
      is a cell-mediated process, possibly caused by the low pH of the phagosome and/or
      the presence of hydrolytic enzymes. In conclusion, we have demonstrated that the
      chemical composition of degrading polymers inside cells can be probed by Raman
      spectral imaging. This technique will expand the capabilities of investigating
      biomaterial degradation in vivo.

PMID- 15479070
TI  - Probing proton-proton proximities in the solid state: high-resolution two
      dimensional 1H-1H double-quantum CRAMPS NMR spectroscopy.
AB  - A new 1H DQ (double-quantum) CRAMPS (combined rotation and multiple-pulse
      sequence) solid-state nuclear magnetic resonance experiment incorporating DUMBO
      homonuclear 1H dipolar decoupling is presented. The major resolution enhancement
      enables DQ peaks corresponding to all 22 close (<3.5 A) proton-proton proximities
      in the dipeptide beta-AspAla to be observed. In particular, the DQ CRAMPS
      spectrum provides access to the alkyl region of the spectrum and yields a clear
      assignment of the two CH and two diastereotopic CH2 proton resonances.

PMID- 15479071
TI  - Site-selective abstraction in the reaction of 5-20 eV O+ with a self-assembled
      monolayer.
AB  - Site-specific reaction of hyperthermal O+ with a self-assembled monolayer is
      described. Isotopic labeling experiments reveal the percentage of abstraction
      products formed from hydrogen atoms bound originally to the top three carbon
      atoms in the chain.

PMID- 15479072
TI  - DNA-mediated charge transport requires conformational motion of the DNA bases:
      elimination of charge transport in rigid glasses at 77 K.
AB  - We have proposed that DNA-mediated charge transport (CT) is gated by base
      motions, with only certain base conformations being CT-active; a CT-active
      conformation can be described as a domain, a transiently extended pi-orbital
      defined dynamically by DNA sequence. Here, to explore these CT-active
      conformations, we examine the yield of base-base CT between photoexcited 2
      aminopurine (Ap*) and guanine in DNA in rigid LiCl glasses at 77 K, where
      conformational rearrangement is effectively eliminated. Duplex DNA assemblies (35
      mers) were constructed containing adenine bridges Ap(A)nG (n = 0-4). The yield of
      CT was monitored through fluorescence quenching of Ap* by G. We find, first, that
      the emission intensity of Ap* in all DNA duplexes increases dramatically upon
      cooling and becomes comparable to free Ap*. This indicates that all quenching of
      Ap* in duplex DNA is a dynamic process that requires conformational motion of the
      DNA bases. Second, DNA-mediated CT between Ap* and G is not observed at 77 K;
      rather than hindering the ability of DNA to transport charge, conformational
      motion is required. Moreover, the lack of DNA-mediated CT at 77 K, even through
      the shortest bridge, suggests that the static structures adopted upon cooling do
      not represent optimum CT-active conformations. These observations are consistent
      with our model of conformationally gated CT. Through conformational motion of the
      DNA bases, CT-active domains form and break-up transiently, both facilitating and
      limiting CT.

PMID- 15479073
TI  - Multiple areas of magnetic bistability in the topological ferrimagnet
      [Co3(NC5H3(CO2)2-2,5)2(mu3-OH)2(OH2)2].
AB  - Hydrothermal reaction of CoCl2 with the potassium salt of pyridine-2,3
      dicarboxylic acid and excess base yields [Co3(NC5H3(CO2)2-2,5)2(mu3-OH)2(OH2)2],
      which has a three-dimensional structure based on hydroxide-bridged triangular
      chains. The magnetic behavior of this compound shows the presence of three
      distinct regions of magnetic bistability.

PMID- 15479074
TI  - Isolation of a Se-nitrososelenol: a new class of reactive nitrogen species
      relevant to protein Se-nitrosation.
AB  - Nitric oxide (NO) is a messenger molecule implicated in a number of physiological
      processes. Nitrosation of selenoproteins has been suggested as playing an
      important role in NO-mediated cellular functions such as the inactivation of
      glutathione peroxidase (GPx), but no chemical information about Se-nitrosated
      species has been available to date. Here a stable Se-nitrososelenol (RSeNO), a
      new class of NO derivative, was synthesized and fully characterized by X-ray
      crystallography and spectroscopic methods. This Se-nitrososelenol can be formed
      by direct transnitrosation from an S-nitrosothiol to a selenol, as is the case in
      the proposed mechanism for the NO-mediated inactivation of GPx.

PMID- 15479075
TI  - Reprogramming DNA-directed reactions on the basis of a DNA conformational change.
AB  - A strategy has been developed for switching chemical reactions between two
      identical reagents on the basis of DNA duplex-triplex transition. In response to
      the change of solution pH, a DNA complex changes its conformation and repositions
      chemical reagents that are conjugated with DNA strands. As a result, chemical
      reactions are reprogrammed. This strategy is expected to be applicable to
      sophisticated chemical syntheses.

PMID- 15479076
TI  - 1,3-Bis(N,N-dialkylamino)imidazolin-2-ylidenes: synthesis and reactivity of a new
      family of stable N-heterocyclic carbenes.
AB  - The synthesis of stable 1,3-bis(N,N-dialkylamino)imidazolin-2-ylidenes was
      accomplished from readily available chiral bis-hydrazones after reduction or
      addition of PhMgCl, cyclization to imidazolinium salts, and treatment with
      KN(SiMe3)2. This strategy allows the obtention of free imidazolin-2-ylidenes and
      their Rh(COD)Cl complexes in enantiomerically pure form. The sigma-donor ability
      of dialkylamino-substituted diaminocarbenes was found to be slightly higher than
      that of alkyl(aryl) analogues.

PMID- 15479077
TI  - Oxidative C-arylation of free (NH)-heterocycles via direct (sp3) C-H bond
      functionalization.
AB  - The development of a new chemical transformation, namely oxidative C-arylation of
      saturated (NH)-heterocycles, is described. This reaction combines dehydrogenation
      and arylation in one process, leading to cross-coupling of (NH)-heterocycles and
      haloarenes. Typical reaction conditions involve heating the reaction partners in
      anhydrous dioxane at 120-150 degrees C in the presence of RhCl(CO)[P(Fur)3]2 as
      the catalyst and Cs2CO3 as the base. Addition of tert-butylethylene as the
      hydrogen acceptor increases the chemical yield by diminishing the dehalogenation
      pathway. This method demonstrated a good substrate scope, allowing for cross
      coupling of a variety of (NH)-heterocycles (e.g., pyrrolidine, piperidine,
      piperazine, morpholine) and halo(hetero)arenes to afford valuable heterocyclic
      products in one step. The preliminary mechanistic studies provided some insight
      regarding the key events in the proposed catalytic cycle, including beta-hydride
      elimination of an amido rhodium complex and carbometalation of the resulting
      imine. A large kinetic isotope effect [KIE (kC-H/kC-D) = 4.3] suggests that one
      or both beta-hydride elimination steps are rate determining. The central role for
      the phosphine ligand was established in controlling the partitioning between the
      oxidative C-arylation and N-arylation pathways.

PMID- 15479078
TI  - Genetic screens and selections for small molecules based on a synthetic
      riboswitch that activates protein translation.
AB  - Genetic selection provides the most powerful method to assay large libraries of
      biomolecules for function. However, harnessing the power of genetic selection for
      the detection of specific, nonendogenous small-molecule targets in vivo remains a
      significant challenge. The ability to genetically select for small molecules
      would provide a reaction-independent mechanism to clone biosynthesis genes from
      large DNA libraries and greatly facilitate the exploration of large libraries of
      mutant enzymes for improved synthetic capabilities including altered substrate
      specificities and enhanced regio- or stereoselectivities. While remarkable
      progress has been made in developing genetic methods to detect small molecules in
      vivo, many of these methods rely on engineering small-molecule-protein
      interactions which remains a difficult problem, and the potential for some of
      these systems to assay large libraries is limited by the low transformation
      efficiency and long doubling time of yeast relative to bacteria. Herein, we
      demonstrate that synthetic riboswitches that activate protein translation in
      response to a specific small molecule can be used to perform sensitive genetic
      screens and selections for the presence of small molecules in Escherichia coli.
      We further demonstrate that the exquisite molecular discrimination properties of
      aptamers selected in vitro translate directly into an in vivo genetic selection
      system. Finally, we demonstrate that a cell harboring a synthetic riboswitch with
      a particular ligand specificity can be selectively amplified from a million-fold
      larger pool of cells containing mutant riboswitches that respond to a closely
      related ligand, suggesting that it is possible to use genetic selection in E.
      coli to discover synthetic riboswitches with new ligand specificities from
      libraries of mutant riboswitches.

PMID- 15479079
TI  - Determining the folding and unfolding rate constants of nucleic acids by
      biosensor. Application to telomere G-quadruplex.
AB  - Nucleic acid molecules may fold into secondary structures, and the formation of
      such structures is involved in many biological processes and technical
      applications. The folding and unfolding rate constants define the kinetics of
      conformation interconversion and the stability of these structures and is
      important in realizing their functions. We developed a method to determine these
      kinetic parameters using an optical biosensor based on surface plasmon resonance.
      The folding and unfolding of a nucleic acid is coupled with a hybridization
      reaction by immobilization of the target nucleic acid on a sensor chip surface
      and injection of a complementary probe nucleic acid over the sensor chip surface.
      By monitoring the time course of duplex formation, both the folding and unfolding
      rate constants for the target nucleic acid and the association and dissociation
      rate constants for the target-probe duplex can all be derived from the same
      measurement. We applied this method to determine the folding and unfolding rate
      constants of the G-quadruplex of human telomere sequence (TTAGGG)(4) and its
      association and dissociation rate constants with the complementary strand
      (CCCTAA)(4). The results show that both the folding and unfolding occur on the
      time scale of minutes at physiological concentration of K(+). We speculate that
      this property might be important for telomere elongation. A complete set of the
      kinetic parameters for both of the structures allows us to study the competition
      between the formation of the quadruplex and the duplex. Calculations indicate
      that the formation of both the quadruplex and the duplex is strand concentration
      dependent, and the quadruplex can be efficiently formed at low strand
      concentration. This property may provide the basis for the formation of the
      quadruplex in vivo in the presence of a complementary strand.

PMID- 15479081
TI  - Incorporating protein flexibility in structure-based drug discovery: using HIV-1
      protease as a test case.
AB  - We have developed a receptor-based pharmacophore method which utilizes a
      collection of protein structures to account for inherent protein flexibility in
      structure-based drug design. Several procedures were systematically evaluated to
      derive the most general protocol for using multiple protein structures. Most
      notably, incorporating more protein flexibility improved the performance of the
      method. The pharmacophore models successfully discriminate known inhibitors from
      drug-like non-inhibitors. Furthermore, the models correctly identify the bound
      conformations of some ligands. We used unliganded HIV-1 protease to develop and
      validate this method. Drug design is always initiated with a protein-ligand
      structure, and such success with unbound protein structures is remarkable -
      particularly in the case of HIV-1 protease, which has a large conformational
      change upon binding. This technique holds the promise of successful computer
      based drug design before bound crystal structures are even discovered, which can
      mean a jump-start of 1-3 years in tackling some medically relevant systems with
      computational methods.

PMID- 15479080
TI  - Kinetic and regiospecific interrogation of covalent intermediates in the
      nonribosomal peptide synthesis of yersiniabactin.
AB  - For interrogation of enzyme-bound intermediates in nonribosomal peptide
      synthetases (NRPSs), mass spectrometry is used to read out the kinetics and
      substrate specificity of this medicinally important class of enzymes. The protein
      HMWP2 (230 kDa) catalyzes 11 chemical reactions, four of which could be resolved
      by fast quench approaches combined with mass spectrometry. The rate of complex
      intermediate accumulation at the PCP1 active site was observed to occur with a
      rate of 19 s(-1), with the rate of cysteine acylation faster than that of
      intermediate translocation. Use of alternative substrates for salicylic acid (at
      the ArCP carrier domain) and l-cysteine (at the PCP1 carrier domain) revealed a
      high penalty for omission of the salicyl alcohol. For some substrates, large
      discrepancies were found between prior adenylation assays and the current MS
      based readouts. Indirect evidence for condensation via a thiolate attack (vs an
      amino group) was also accumulated. This is the first report to correlate the
      percent occupancy of multiple active sites in parallel with kinetic and
      structural resolution of intermediates and provides new evidence of interdomain
      and intermodule communication within thiotemplate assembly lines.

PMID- 15479082
TI  - Engineered protein cages for nanomaterial synthesis.
AB  - Self-assembled particles of genetically engineered human L subunit ferritin
      expressing a silver-binding peptide were used as nanocontainers for the synthesis
      of silver nanoparticles. The inner cavity of the self-assembled protein cage
      displays a dodecapeptide that is capable of reducing silver ions to metallic
      silver. This chimeric protein cage when incubated in the presence of silver
      nitrate exhibits the growth of a silver nanocrystal within its cavity. Our
      studies indicate that it is possible to design chimeric cages, using specific
      peptide templates, for the growth of other inorganic nanoparticles.

PMID- 15479083
TI  - Independent generation of the 5-hydroxy-5,6-dihydrothymidin-6-yl radical and its
      reactivity in dinucleoside monophosphates.
AB  - Hydroxyl radical is a major reactive oxygen species produced by gamma-radiolysis
      of water or Fenton reaction. It attacks pyrimidine bases and gives the 5-hydroxy
      5,6-dihydropyrimidin-6-yl radical as the major product. Here we report the
      synthesis of all four stereoisomers of 5-hydroxy-6-phenylthio-5,6
      dihydrothymidine (T*), which, upon 254 nm UV irradiation, give rise to the 5
      hydroxy-5,6-dihydrothymidin-6-yl radical (I). We also incorporated the
      photolabile radical precursors into dinucleoside monophosphates d(GT*) and d(TT*)
      and characterized major products resulting from the 254-nm irradiation of these
      dinucleoside monophosphates. Our results showed that, under anaerobic conditions,
      the most abundant product emanating from the 254-nm irradiation of d(GT*) and
      d(TT*) is an abasic site lesion. Products with the thymine portion being modified
      to thymine glycol and 5-hydroxy-5,6-dihydrothymine were also observed. In
      addition, we demonstrated that radical I can attack the C8 carbon atom of its 5'
      neighboring guanine and give rise to a novel cross-link lesion. Moreover, LC
      MS/MS results showed that gamma-radiation of d(GT) under anaerobic condition
      yielded the same type of cross-link lesions.

PMID- 15479084
TI  - A two-unnatural-base-pair system toward the expansion of the genetic code.
AB  - Toward the site-specific incorporation of amino acid analogues into proteins, a
      two-unnatural-base-pair system was developed for coupled transcription
      translation systems with the expanded genetic code. A previously designed
      unnatural base pair between 2-amino-6-(2-thienyl)purine (denoted by s) and
      pyridin-2-one (denoted by y) was used for the site-specific incorporation of yTP
      into RNA opposite s in templates by T7 RNA polymerase. For the site-specific
      incorporation of sTP into RNA, a newly developed unnatural base, imidazolin-2-one
      (denoted by z), is superior to y as a template base for pairing with s in T7
      transcription. The combination of the s-y and s-z pairs provides a powerful tool
      to prepare both y-containing mRNA and s-containing tRNA for efficient coupled
      transcription-translation systems, in which the genetic code is expanded by the
      codon-anticodon interactions mediated by the s-y pair. In addition, the
      nucleoside of s is strongly fluorescent, and thus the s-z pair enables the site
      specific fluorescent labeling of RNA molecules. These unnatural-base-pair studies
      provide valuable information for understanding the mechanisms of replication and
      transcription.

PMID- 15479085
TI  - Inhibition of peptidylglycine alpha-amidating monooxygenase by exploitation of
      factors affecting the stability and ease of formation of glycyl radicals.
AB  - Peptidylglycine alpha-amidating monooxygenase catalyzes the biosynthesis of
      peptide hormones through radical cleavage of the C-terminal glycine residues of
      the corresponding prohormones. We have correlated ab initio calculations of
      radical stabilization energies and studies of free radical brominations with the
      extent of catalysis displayed by peptidylglycine alpha-amidating monooxygenase,
      to identify classes of inhibitors of the enzyme. In particular we find that, in
      closely related systems, the substitution of glycolate for glycine reduces the
      calculated radical stabilization energy by 34.7 kJ mol(-1), decreases the rate of
      bromination with N-bromosuccinimide at reflux in carbon tetrachloride by a factor
      of at least 2000, and stops catalysis by the monooxygenase, while maintaining
      binding to the enzyme.

PMID- 15479086
TI  - p-Menthane-3-carboxaldehyde: a useful chiral auxiliary for the synthesis of
      chiral quaternary carbons of high enantiomeric purity.
AB  - (+)- or (-)-p-Menthane-3-carboxaldehyde is made in two easy steps from (+)- or (
      )-menthone, respectively. This auxiliary allows for the synthesis of carbonyl
      compounds bearing a alpha-chiral quaternary carbon. The flexibility, efficiency,
      and ease of use of the method are demonstrated in a series of examples, which
      include the total synthesis of (+)-cuparenone as well as a partial synthesis of (
      )-cassiol.

PMID- 15479087
TI  - Orientation and alkylation effects on cation-pi interactions in aqueous solution.
AB  - We have investigated the orientation dependence of the cation-pi interaction
      between a phenyl ring and a pyridinium ring in the context of a flexible model
      system in water. Of the four possible positions of the pyridinium nitrogen, ipso,
      ortho, meta, and para, we found a variation in the interaction energy of about
      0.75 kcal mol(-1), with the stacking of the ipso-pyridinium ring providing the
      strongest interaction. The observed stability is attributed to the maximization
      of the electrostatic interaction, minimization of rotamers, and possible
      differences in hydration phenomena arising from alkylation.

PMID- 15479088
TI  - Experimental and theoretical studies of the propargyl-allenylindium system.
AB  - The transient organoindium intermediates formed in the reaction of propargyl
      bromide with indium in aqueous media and tetrahydrofuran were investigated by NMR
      spectroscopy and found to be allenylindium(I) and allenylindium(III) dibromide.
      The influence of solvent and methyl substitution on the propargyl-allenylindium
      system was also studied. The experimental observations were supported by
      theoretical calculations using the B3LYP/6-311+G* method.

PMID- 15479089
TI  - Crystal engineering approach to forming cocrystals of amine hydrochlorides with
      organic acids. Molecular complexes of fluoxetine hydrochloride with benzoic,
      succinic, and fumaric acids.
AB  - A crystal engineering strategy for designing cocrystals of pharmaceuticals is
      presented. The strategy increases the probability of discovering useful
      cocrystals and decreases the number of experiments that are needed by selecting
      API:guest combinations that have the greatest potential of forming energetically
      and structurally robust interactions. Our approach involves multicomponent
      cocrystallization of hydrochloride salts, wherein strong hydrogen bond donors are
      introduced to interact with chloride ions that are underutilized as hydrogen bond
      acceptors. The strategy is particularly effective in producing cocrystals of
      amine hydrochlorides with neutral organic acid guests. As an example of the
      approach, we report the discovery of three cocrystals containing fluoxetine
      hydrochloride (1), which is the active ingredient in the popular antidepressant
      Prozac. A 1:1 cocrystal was prepared with 1 and benzoic acid (2), while succinic
      acid and fumaric acid were each cocrystallized with 1 to provide 2:1 cocrystals
      of fluoxetine hydrochloride:succinic acid (3) and fluoxetine
      hydrochloride:fumaric acid (4). The presence of a guest molecule along with
      fluoxetine hydrochloride in the same crystal structure results in a solid phase
      with altered physical properties when compared to the known crystalline form of
      fluoxetine hydrochloride. On the basis of intrinsic dissolution rate experiments,
      cocrystals 2 and 4 dissolve more slowly than 1, and 3 dissolves more quickly than
      1. Powder dissolution experiments demonstrated that the solid present at
      equilibrium corresponds to the cocrystal for 2 and 4, while 3 completely
      converted to 1 upon prolonged slurry in water.

PMID- 15479090
TI  - Detection of bacteria with carbohydrate-functionalized fluorescent polymers.
AB  - Many pathogens that infect humans use cell surface carbohydrates as receptors to
      facilitate cell-cell adhesion. The hallmark of these interactions is their
      multivalency, or the simultaneous occurrence of multiple interactions. We have
      used a carbohydrate-functionalized fluorescent polymer, which displays many
      carbohydrate ligands on a single polymer chain, to allow for multivalent
      detection of pathogens. Incubation of a mannose-functionalized polymer with
      Escherichia coli yields brightly fluorescent aggregates of bacteria. These
      results show that carbohydrate-functionalized fluorescent polymers are a
      versatile detection method for bacteria. Future design of detectors for other
      pathogens only requires information on the carbohydrates bound by the organisms,
      which has been exhaustively reported in the literature.

PMID- 15479091
TI  - Impact of molecular speciation on crystal nucleation in polymorphic systems: the
      conundrum of gamma glycine and molecular 'self poisoning'.
AB  - The polymorphism of the simple amino acid glycine has been known for almost a
      century. It is also known that in aqueous solutions, at the isoelectric point (pI
      5.9), the metastable alpha polymorph crystallizes, while the stable gamma form of
      glycine only nucleates at high and low pH. Despite the importance of
      understanding the process by which crystals nucleate, the solution and solid
      state chemistry underlying this simple observation have never been explored. In
      this contribution, we have combined solution chemistry, crystallization, and
      crystallographic data to investigate the mechanisms by which this effect occurs.
      It is concluded that solution speciation and the consequent interactions between
      charged species and developing crystal nuclei determine the structural outcome of
      the crystallization process.

PMID- 15479092
TI  - Chiral recognition of dipeptides in a biomembrane model.
AB  - Chiral recognition of the enantiomeric couples of ditryptophan and
      diphenylalanine was observed by (1)H NMR spectroscopy in micelles formed by
      sodium N-dodecanoyl-L-prolinate. Ditryptophan showed a selective association with
      the Z domains of the amidic aggregates, whereas diphenylalanine did not show any
      selectivity in the association. Partition coefficients between water and
      aggregates were evaluated by diffusion NMR experiments. Intramolecular distances
      of ditryptophan isomers associated with chiral aggregates were obtained by ROESY
      experiments and were used as constraints in molecular mechanics calculations.
      From these calculations, information on the conformation of the peptides in the
      chiral aggregates was obtained.

PMID- 15479093
TI  - Electronic modulation of dithienothiophene (DTT) as pi-center of D-pi-D
      chromophores on optical and redox properties: analysis by UV-Vis-NIR and Raman
      spectroscopies combined with electrochemistry and quantum chemical DFT
      calculations.
AB  - In this paper, we study three symmetrical D-pi-D chromophores containing
      dithieno[3,2-b:2',3'-d]thiophene (DTT) as the pi-center and various donor end
      moieties, by means of UV-vis-NIR and FT-Raman spectroscopy and in situ
      spectroelectrochemistry. The compounds display dual redox properties: all
      exhibited two oxidations and single stable reduction peaks contrarily to the one
      or two oxidations and none reduction which could be anticipated in view of their
      chemical structures. We analyze the possible electronic modulation by the pi
      conjugated DTT relay in the redox process and electronic coupling between the two
      electron donor (D) units attached through conjugation to opposite sides of the pi
      linker. To this end, the UV-vis-NIR and FT-Raman spectra of the neutral compounds
      and of the charged species generated upon in situ p- or n-doping have been
      recorded and interpreted with the help of Density Functional Theory (DFT)
      calculations. The analysis of the peculiar Raman features of these pi-conjugated
      chromophores is guided by the formalism of the Effective Conjugation Coordinate
      (ECC) theory. This research shows that the Raman spectroscopic characterization
      of this type of D-pi-D structures is a powerful tool to derive information about
      their pi-conjugational properties in the pristine and doped states.

PMID- 15479094
TI  - Metal chelation-controlled twisted intramolecular charge transfer and its
      application to fluorescent sensing of metal ions and anions.
AB  - Two fluorescent ligands, N-(2-(5-cyanopyridyl))cyclen (L5) and N-(2
      pyridyl)cyclen (L6) (cyclen = 1,4,7,10-tetraazacyclododecane), were designed and
      synthesized to control twisted intramolecular charge transfer (TICT) by metal
      chelation in aqueous solution. By complexation with Zn(2+), L6 exhibited TICT
      emissions at 430 nm (excitation at 270 nm) in 10 mM HEPES (pH 7.0) with I = 0.1
      (NaNO(3)) at 25 degrees C due to the perpendicular conformation of a pyridine
      ring with respect to a dialkylamino group, which was fixed by Zn(2+)-N(pyridine)
      coordination, as proven by potentiometric pH, UV, and fluorescence titrations and
      X-ray crystal structure analysis. We further describe that the 1:1 complexation
      of ZnL6 with guests such as succinimide, phosphates, thiolates, and
      dicarboxylates, which compete with a nitrogen in the pyridine ring for Zn(2+) in
      ZnL6, induces considerable emission shift from TICT emissions (at 430 nm) to
      locally excited emissions (at ca. 350 nm) in neutral aqueous solution at 25
      degrees C.

PMID- 15479095
TI  - Detailed structural investigation of the grafting of [Ta(=CHtBu)(CH2tBu)3] and
      [Cp*TaMe4] on silica partially dehydroxylated at 700 degrees C and the activity
      of the grafted complexes toward alkane metathesis.
AB  - The reaction of [Ta(=CHtBu)(CH2tBu)3] or [Cp*Ta(CH3)4] with a silica partially
      dehydroxylated at 700 degrees C gives the corresponding monosiloxy surface
      complexes [([triple bond]SiO)Ta(=CHtBu)(CH2tBu)2] and [([triple
      bond]SiO)Ta(CH3)3Cp*] by eliminating a sigma-bonded ligand as the corresponding
      alkane (H-CH2tBu or H-CH3). EXAFS data show that an adjacent siloxane bridge of
      the surface plays the role of an extra surface ligand, which most likely
      stabilizes these complexes as in [([triple bond]SiO)Ta(=CHtBu)(CH2tBu)2([triple
      bond]SiOSi[triple bond])] (1a') and [([triple bond]SiO)Ta(CH3)3Cp*([triple
      bond]SiOSi[triple bond])] (2a'). In the case of [(SiO)Ta(=CHtBu)(CH2tBu)2([triple
      bond]SiOSi[triple bond])], the structure is further stabilized by an additional
      interaction: a C-H agostic bond as evidenced by the small J coupling constant for
      the carbenic C-H (JC-H = 80 Hz), which was measured by J-resolved 2D solid-state
      NMR spectroscopy. The product selectivity in propane metathesis in the presence
      of [([triple bond]SiO)Ta(=CHtBu)(CH2tBu)2([triple bond]SiOSi[triple bond])] (1a')
      as a catalyst precursor and the inactivity of the surface complex [([triple
      bond]SiO)Ta(CH3)3Cp*([triple bond]SiOSi[triple bond])] (2a') show that the active
      site is required to be highly electrophilic and probably involves a
      metallacyclobutane intermediate.

PMID- 15479097
TI  - Photocatalytic H2 evolution reaction from aqueous solutions over band structure
      controlled (AgIn)xZn2(1-x)S2 solid solution photocatalysts with visible-light
      response and their surface nanostructures.
AB  - (AgIn)(x)Zn(2(1-x))S(2) solid solutions between ZnS photocatalyst with a wide
      band gap and AgInS(2) with a narrow band gap showed photocatalytic activities for
      H(2) evolution from aqueous solutions containing sacrificial reagents, SO(3)(2)(
      ) and S(2)(-), under visible-light irradiation (lambda >or= 420 nm) even without
      Pt cocatalysts. Loading of the Pt cocatalysts improved the photocatalytic
      activity. Pt (3 wt %)-loaded (AgIn)(0.22)Zn(1.56)S(2) with a 2.3 eV band gap
      showed the highest activity for H(2) evolution, and the apparent quantum yield at
      420 nm amounted to 20%. H(2) gas evolved at a rate of 3.3 L m(-2) x h(-1) under
      irradiation using a solar simulator (AM 1.5). The diffuse reflection and the
      photoluminescence spectra of the solid solutions shifted monotonically to a long
      wavelength side as the ratio of AgInS(2) to ZnS increased in the solid solutions.
      The photocatalytic H(2) evolution depended on the compositions as well as the
      photophysical properties. The dependence of the photophysical and photocatalytic
      properties upon the composition was mainly due to the change in the band position
      caused by the contribution of the Ag 4d and In 5s5p orbitals to the valence and
      conduction bands, respectively. It was found from SEM and TEM observations that
      the solid solutions partially had nanostep structures on their surfaces. The Pt
      cocatalysts were selectively photodeposited on the edge of the surface nanosteps.
      It was suggested that the specific surface nanostructure was effective for the
      suppression of recombination between photogenerated electrons and holes and for
      the separation of H(2) evolution sites from oxidation reaction sites.

PMID- 15479096
TI  - Self-assembly of biocidal nanotubes from a single-chain diacetylene amine salt.
AB  - We describe the facile two-step synthesis of nanotubes that form pure, well
      defined, nanostructured materials. We have synthesized a secondary amine HBr salt
      as the headgroup of a single-chain diacetylenic lipid. This molecule can form a
      number of different self-assembled nanostructures in aqueous or organic solvents.
      In water, this lipid forms a monodisperse preparation of nanotubes at high
      yields. Partially dissolving a preparation of nanotubes dried from aqueous
      solution results in a remarkably organized structure that resembles a nanocarpet.
      Details of the nanotube structure were investigated by scanning electron
      microscopy, transmission electron microscopy, and small-angle X-ray spectroscopy.
      The aqueous nanotubes have a cross-sectional diameter of 89 nm. The walls of the
      tubes are an exquisitely uniform 27 nm thick and are shown to consist of five
      lipid bilayers with a repeat spacing of 57.8 A. The chemical structure of the
      material shows no chiral centers, but suspensions of the nanotubes in an aqueous
      medium show an unexpected circular dichroism signal. The versatility of this new
      material as a platform for nanostructure design and synthesis is enhanced by its
      biocidal activity. This antimicrobial activity along with the regularity the
      nanostructures will enhance the development of a range of applications from
      biosensors to artificial retinas.

PMID- 15479098
TI  - Synthesis, characterization, and framework heteroatom localization in ITQ-21.
AB  - ITQ-21 has been synthesized in a wide range of compositions. By rationally
      modifying the synthesis variables and zeolite composition, it is possible to fine
      tune the crystallite size from nanocrystals (<80 nm) up to microns and to avoid
      the competition of other phases such as CIT-5, SSZ-24, or a laminar phase that
      can also be synthesized with the same organic structure directing agent. By means
      of XRD and (19)F MAS NMR, Ge and Si have been localized among the different
      crystallographic positions, and it is shown that Ge preferentially occupies T1
      positions at the D4R cages, avoiding formation of Ge-O-Ge pairs. However, at high
      Ge loadings (Si/Ge = 1.7), a new (19)F MAS NMR signal at -14 ppm has been
      observed and assigned to the presence of Ge-O-Ge in Ge-rich D4R cages. Energetic
      configurations obtained by theoretical calculations fully agree with experimental
      observations, with the following increasing order in energy for Ge substitution:
      T1 < T2 < Ge-O-Ge in T1 < T3.

PMID- 15479099
TI  - Catalytic nanomotors: autonomous movement of striped nanorods.
AB  - Rod-shaped particles, 370 nm in diameter and consisting of 1 microm long Pt and
      Au segments, move autonomously in aqueous hydrogen peroxide solutions by
      catalyzing the formation of oxygen at the Pt end. In 2-3% hydrogen peroxide
      solution, these rods move predominantly along their axis in the direction of the
      Pt end at speeds of up to 10 body lengths per second. The dimensions of the rods
      and their speeds are similar to those of multiflagellar bacteria. The force along
      the rod axis, which is on the order of 10(-14) N, is generated by the oxygen
      concentration gradient, which in turn produces an interfacial tension force that
      balances the drag force at steady state. By solving the convection-diffusion
      equation in the frame of the moving rod, it was found that the interfacial
      tension force scales approximately as SR(2)gamma/muDL, where S is the area
      normalized oxygen evolution rate, gamma is the liquid-vapor interfacial tension,
      R is the rod radius, mu is the viscosity, D is the diffusion coefficient of
      oxygen, and L is the length of the rod. Experiments in ethanol-water solutions
      confirmed that the velocity depends linearly with the product Sgamma, and scaling
      experiments showed a strong dependence of the velocity on R and L. The direction
      of motion implies that the gold surface is hydrophobic under the conditions of
      the experiment. Tapping-mode AFM images of rods in air-saturated water show soft
      features that are not apparent in images acquired in air. These features are
      postulated to be nanobubbles, which if present in hydrogen peroxide solutions,
      would account for the observed direction of motion.

PMID- 15479101
TI  - Local and nanoscale structure and speciation in the PuO2+x-y(OH)2y.zH2O system.
AB  - Pu L(3) X-ray absorption fine structure spectra from 24 samples of PuO(2+x) (and
      two related Pu-substituted oxides), prepared by a variety of methods, demonstrate
      that (1) although the Pu sublattice remains the ordered part of the Pu
      distribution, the nearest-neighbor O atoms even at x = 0 are found in a multisite
      distribution with Pu-O distances consistent with the stable incorporation of OH(
      ) (and possibly H(2)O and H(+)) into the PuO(2) lattice; (2) the excess O from
      oxidation is found at Pu-O distances <1.9 A, consistent with the multiply bound
      "oxo"-type ligands found in molecular complexes of Pu(V) and Pu(VI); (3) the Pu
      associated with these oxo groups is most likely Pu(V), so that the excess O
      probably occurs as PuO(2)(+) moieties that are aperiodically distributed through
      the lattice; and (4) the collective interactions between these defect sites most
      likely cause them to cluster so as give nanoscale heterogeneity in the form of
      domains that may have unusual reactivity, observed as sequential oxidation by
      H(2)O at ambient conditions. The most accurate description of PuO(2) is therefore
      actually PuO(2+x-y)(OH)(2)(y).zH(2)O, with pure, ordered, homogeneous PuO(2)
      attained only when H(2)O is rigorously excluded and the O activity is relatively
      low.

PMID- 15479100
TI  - Metal-catalyzed anaerobic disproportionation of hydroxylamine. Role of diazene
      and nitroxyl intermediates in the formation of N2, N2O, NO+, and NH3.
AB  - The catalytic disproportionation of NH(2)OH has been studied in anaerobic aqueous
      solution, pH 6-9.3, at 25.0 degrees C, with Na(3)[Fe(CN)(5)NH(3)].3H(2)O as a
      precursor of the catalyst, [Fe(II)(CN)(5)H(2)O](3)(-). The oxidation products are
      N(2), N(2)O, and NO(+) (bound in the nitroprusside ion, NP), and NH(3) is the
      reduction product. The yields of N(2)/N(2)O increase with pH and with the
      concentration of NH(2)OH. Fast regime conditions involve a chain process
      initiated by the NH(2) radical, generated upon coordination of NH(2)OH to
      [Fe(II)(CN)(5)H(2)O](3)(-). NH(3) and nitroxyl, HNO, are formed in this fast
      process, and HNO leads to the production of N(2), N(2)O, and NP. An intermediate
      absorbing at 440 nm is always observed, whose formation and decay depend on the
      medium conditions. It was identified by UV-vis, RR, and (15)NMR spectroscopies as
      the diazene-bound [Fe(II)(CN)(5)N(2)H(2)](3)(-) ion and is formed in a
      competitive process with the radical path, still under the fast regime. At high
      pH's or NH(2)OH concentrations, an inhibited regime is reached, with slow
      production of only N(2) and NH(3). The stable red diazene-bridged
      [(NC)(5)FeHN=NHFe(CN)(5)](6)(-) ion is formed at an advanced degree of NH(2)OH
      consumption.

PMID- 15479102
TI  - Electrostatic influence on rotational mobilities of sol-gel-encapsulated solutes
      by NMR and EPR spectroscopies.
AB  - The rotational mobilities of small solute molecules encapsulated in tetramethyl
      orthosilicate (TMOS) sol-gels have been investigated by EPR spectroscopy of
      encapsulated nitroxide probes and by high-resolution NMR spectroscopic
      measurements of transferred NOE's (trNOE's), of T(1)'s, and of T(1)'s in the
      rotating frame (T(1)rho). The two spectroscopic methods are sensitive to motions
      on different time scales and hence, are nicely complementary. Suites of neutral,
      positively, and negatively charged nitroxide probes (EPR) and of simple
      diamagnetic small molecules (NMR) were selected to disclose influences of
      electrostatic interactions with the sol-gel walls and to probe the presence of
      multiple populations of molecules in distinct regions of the sol-gel pores. For
      neutral and negatively charged solute probes, both techniques disclose a single
      population with a significantly increased average rotational correlation time,
      which we interpret at least in part as resulting from exchange between free
      volume and transiently immobilized surface populations. The electrostatic
      attraction between cationic probes and the negatively charged sol-gel walls
      causes the positively charged probes to be more effectively immobilized and/or
      causes a greater percentage of probes to undergo this transient immobilization.
      The EPR spectra directly disclose a population of cationic probes which are
      immobilized on the X-band EPR time scale: tau(c) greater than or approximately
      equal 10(-7) s. However, NMR measurements of trNOE's and of T(1)rho demonstrate
      that this population does exchange with the free-volume probes on the slower time
      scale of NMR. This approach is equally applicable to the study of solutes within
      other types of confined spaces, as well.

PMID- 15479103
TI  - Dioxygen activation by a low-valent cobalt complex employing a flexible tripodal
      N-heterocyclic carbene ligand.
AB  - The novel versatile cobalt(I) tris-carbene complex [(TIMEN(xyl))Co]Cl (1) (where
      TIMEN = (tris[2-(3-arylimidazol-2-ylidene)ethyl]amine) reacts with CO, one
      electron oxidizers such as CH(2)Cl(2), and O(2) to yield the cobalt complexes
      [(TIMEN(xyl))Co(CO)]Cl (2), [(TIMEN(xyl))Co(Cl)]Cl (3), and peroxo species
      [(TIMEN(xyl))Co(O(2))](BPh(4)) (5). All new complexes were fully characterized by
      (1)H NMR, UV/vis, and IR spectroscopy as well as superconducting quantum
      interference device (SQUID) magnetization measurements and single-crystal X-ray
      crystallography. The nucleophilic character of the eta(2)-bound dioxygen ligand
      in 5 was confirmed by density functional theory (DFT) studies and allows for
      oxygen-transfer reactions with electron-deficient organic substrates, such as
      benzoyl chloride.

PMID- 15479104
TI  - DNA hybridization assays using temperature gradient focusing and peptide nucleic
      acids.
AB  - Two types of DNA hybridization assays are demonstrated with temperature gradient
      focusing (TGF) and peptide nucleic acids (PNAs). In TGF, the application of a
      controlled temperature gradient along the length of a microchannel filled with an
      appropriate temperature-dependent buffer results in the formation of a gradient
      in both the electric field and electrophoretic velocity. Ionic species move in
      this gradient and concentrate at a unique point where the total velocity sums to
      zero. The first assay is a mixing assay in which PNA is allowed to flow through
      spatially focused DNA targets within a capillary. The second assay detects single
      base pair mutations (SBPM) by monitoring the fluorescence intensity of PNA/DNA
      duplexes as a function of temperature within the capillary. The SBPM analysis can
      be performed in less than 5 min with 100-fold more dilute analyte compared to
      conventional UV melting measurements.

PMID- 15479105
TI  - Building blocks for N-type molecular and polymeric electronics. Perfluoroalkyl-
      versus alkyl-functionalized oligothiophenes (nTs; n = 2-6). Systematic synthesis,
      spectroscopy, electrochemistry, and solid-state organization.
AB  - The synthesis, comparative physicochemical properties, and solid-state structures
      of five oligothiophene (nT) series differing in substituent nature and
      attachment, regiochemistry, and oligothiophene core length (n) are described.
      These five series include the following 25 compounds: (i) alpha,omega
      diperfluorohexyl-nTs 1 (DFH-nTs, n = 2-6), (ii) beta,beta'-diperfluorohexyl-nTs 2
      (isoDFH-nTs, n = 2-6), (iii) alpha,omega-dihexyl-nTs 3 (DH-nTs, n = 2-6), (iv)
      beta,beta'-dihexyl-nTs 4 (isoDH-nTs, n = 2-6), and (v) unsubstituted
      oligothiophenes 5 (alphanTs, n = 2-6). All new compounds were characterized by
      elemental analysis, mass spectrometry, and multinuclear NMR spectroscopy. To
      probe and address quantitatively how the chemistry and regiochemistry of
      conjugated core substitution affects molecular and solid-state properties, the
      entire 1-5 series was investigated by differential scanning calorimetry,
      thermogravimetric analysis, and optical absorption and emission spectroscopies.
      Single-crystal X-ray diffraction data for several fluorocarbon-substituted
      oligomers are also presented and compared. The combined analysis of these data
      indicates that fluorocarbon-substituted nT molecules strongly interact in the
      condensed state, with unit cell level phase separation between the aromatic core
      and fluorocarbon chains. Surprisingly, despite these strong intermolecular
      interactions, high solid-state fluorescence efficiencies are exhibited by the
      fluorinated derivatives. Insight into the solution molecular geometries and
      conformational behavior are obtained from analysis of optical and variable
      temperature NMR spectra. Finally, cyclic voltammetry data offer a reliable
      picture of frontier MO energies, which, in combination with DFT computations,
      provide key information on relationships between oligothiophene substituent
      effects and electronic response properties.

PMID- 15479106
TI  - A sequential molecular mechanics/quantum mechanics study of the electronic
      spectra of amides.
AB  - We report gas-phase electronic spectra of formamide, N-methyformamide, acetamide,
      and N-methylacetamide at 300 K calculated using a combination of classical
      molecular dynamics and time-dependent density functional theory (TDDFT). In
      comparison to excitation energies computed using the global minima structures,
      the valence npi* and pi(nb)pi* states show a significant red-shift of 0.1-0.35
      eV, while smaller shifts are found for the n3s and pi(nb)3s Rydberg states. In
      this work, we have identified the physical origin of these shifts arising from
      variations of the molecular structure. We present simple relationships between
      key geometrical parameters and spectral shifts. Consequently, electronic spectra
      can be generated directly from ground-state structures, without additional
      quantum chemical calculations. The electronic spectrum of formamide in aqueous
      solution is computed using TDDFT using an explicit solvent model. This provides a
      quantitative determination of the condensed-phase spectrum. In general, this
      study shows that temperature effects can change the predicted excitation energies
      significantly and demonstrates how electronic spectra at elevated temperatures
      can be computed in a computationally efficient way.

PMID- 15479107
TI  - Helical folding of alkanes in a self-assembled, cylindrical capsule.
AB  - The reversible encapsulation of a series of normal alkane guests in a cylindrical
      host was studied by NMR methods. For small hydrocarbons such as n-pentane or n
      hexane, two guests enter the host, and they move freely within. With n-heptane no
      encapsulation takes place. For longer alkanes such as n-decane, a single guest
      enters and the aromatic walls of the host are seen to twist to avoid empty spaces
      and increase favorable interactions with the hydrocarbon. The best guest (n
      undecane) adopts a conformation with minimal gauche interactions. The longest
      alkane accommodated, n-tetradecane, adopts a helical conformation to fit in the
      cavity, a shape that maximizes CH/pi interactions with the aromatic walls of the
      receptor. These reciprocal conformational changes are discussed in terms of
      optimal host/guest interactions.

PMID- 15479108
TI  - Enol-enamine tautomerism in crystals of 1,3-bis(pyridin-2-yl) propan-2-one: a
      combined crystallographic and quantum-chemical investigation of the effect of
      packing on tautomerization processes.
AB  - The enolpyridine, OH-ketoenamime, NH equilibrium in crystals of 1,3-bis(pyridin-2
      yl)propan-2-one was studied using temperature-dependent single-crystal X-ray
      diffraction. The relative population of the different tautomers was found to be
      sensitive to the temperature in the range of 100-300 K, illustrating the small
      thermodynamic difference between these two tautomers. This energy resemblance is
      partially attributed to the molecular packing in the crystal, where the molecules
      are arranged in the form of dimers. Ab initio electronic energy calculations
      (HF/6-31G** and MP2/6-31G**) reveal the effect of dimerization in the crystal on
      the electronic energy levels. Several tautomeric states were identified in the
      dimer of 1,3-bis(pyridin-2-yl)propan-2-one. A model is proposed in which four of
      these dimer states are populated in the crystal at ambient temperatures. The
      crystallographic data were treated according to this four-state dimer model,
      suggesting that the free energy of the OH-NH dimers is higher than that of the OH
      OH dimers by 120 +/- 10 cal mol(-1) and that the NH-NH dimers are yet higher in
      free energy by 50 +/- 10 cal mol(-1).

PMID- 15479109
TI  - Extensive migration of Ni and Mn by lithiation of ordered LiMg0.1Ni0.4Mn(1.5)O4
      spinel.
AB  - Li(x)Mg(0.1)Ni(0.4)Mn(1.5)O(4) spinel (P4(3)32) was chemically and
      electrochemically lithiated in the range 1 < x <or= 2.25 and subjected to
      detailed X-ray and neutron diffraction analysis to understand the electrochemical
      behavior in the 3 V region. Extensive migration of Ni and Mn during lithium
      insertion was found, resulting in the disappearance of the initial Ni-Mn ordering
      and the formation of Ni-rich and Ni-poor domains, leading to two Jahn-Teller
      distorted tetragonal phases with different Ni:Mn ratios. Such extensive Ni and Mn
      migration was not known for these spinels, and strongly influences the initial
      cycling behavior. The newly formed tetragonal phase with a Ni:Mn ratio of
      approximately 0.07 has a higher cyclability and a higher capacity, and is
      therefore suggested to have a favorable composition for this intercalation range,
      as is confirmed in the literature. In addition, lithium is found to occupy
      multiple positions inside the distorted oxygen octahedron of this phase, a
      finding previously known only for lithium in anatase TiO(2).

PMID- 15479110
TI  - Amyloid-beta binds Cu2+ in a mononuclear metal ion binding site.
AB  - Amyloid-beta (Abeta) peptide is the principal constituent of plaques associated
      with Alzheimer's disease and is thought to be responsible for the neurotoxicity
      associated with the disease. Metal ions have been hypothesized to play a role in
      the formation and neurotoxicity of aggregates associated with Alzheimer's disease
      (Bush, A. I.; et al. Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 11934). Elucidation
      of the chemistry through which transition-metal ions participate in the assembly
      and toxicity of Abeta oligomers is important to drug design efforts if inhibition
      of Abeta containing bound metal ions becomes a treatment for Alzheimer's disease.
      In this paper, we report electron paramagnetic resonance (EPR) spectroscopic
      characterization of Cu(2+) bound to soluble and fibrillar Abeta. Addition of
      stoichiometric amounts of Cu(2+) to soluble Abeta produces an EPR signal at 10 K
      with observable Cu(2+) hyperfine lines. A nearly identical spectrum is observed
      for Abetafibrils assembled in the presence of Cu(2+). The EPR parameters are
      consistent with a Type 2 Cu(2+) center with three nitrogen donor atoms and one
      oxygen donor atom in the coordination sphere of Cu(2+): g( parallel) = 2.26 and
      A( parallel) = 174 +/- 4 G for soluble Abeta with Cu(2+), and g( parallel) = 2.26
      and A( parallel) = 175 +/- 1 G for Abeta fibrils assembled with Cu(2+).
      Investigation of the temperature dependence of the EPR signal for Cu(2+) bound to
      soluble Abetaor Cu(2+) in fibrillar Abeta shows that the Cu(2+) center displays
      normal Curie behavior, indicating that the site is a mononuclear Cu(2+) site.
      Fibrils assembled in the presence of Cu(2+) contain one Cu(2+) ion per peptide.
      These results show that the ligand donor atom set to Cu(2+) does not change
      during organization of Abetamonomers into fibrils and that neither soluble nor
      fibrillar forms of Abeta(1-40) with Cu(2+) contain antiferromagnetically exchange
      coupled binuclear Cu(2+) sites in which two Cu(2+) ions are bridged by an
      intervening ligand.

PMID- 15479111
TI  - Valence bond calculations of hydrogen transfer reactions: a general predictive
      pattern derived from theory.
AB  - Hydrogen abstraction reactions of the type X(*) + H-H' --> X-H + H'(*) (X = F,
      Cl, Br, I) are studied by ab initio valence bond methods and the VB state
      correlation diagram (VBSCD) model. The reaction barriers and VB parameters of the
      VBSCD are computed by using the breathing orbital valence bond and valence bond
      configuration interaction methods. The combination of the VBSCD model and
      semiempirical VB theory leads to analytical expressions for the barriers and
      other VB quantities that match the ab initio VB calculations fairly well. The
      barriers are influenced by the endo- or exothermicity of the reaction, but the
      fundamental factor of the barrier is the average singlet-triplet gap of the bonds
      that are broken or formed in the reactions. Some further approximations lead to a
      simple formula that expresses the barrier for nonidentity and identity hydrogen
      abstraction reactions as a function of the bond strengths of reactants and
      products. The semiempirical expressions are shown to be useful not only for the
      model reactions that are studied in this work, but also for other nonidentity and
      identity hydrogen abstraction reactions that have been studied in previous
      articles.

PMID- 15479112
TI  - Determination of rate constants for charge transfer and the distribution of
      semiconductor and electrolyte electronic energy levels in dye-sensitized solar
      cells by open-circuit photovoltage decay method.
AB  - A combination of electron lifetime measurement in nanoparticles as a function of
      the Fermi level position at high resolution in the potential scale with a new
      model to describe this dependence provides a powerful tool to study the
      microscopic processes and parameters governing recombination in dye-sensitized
      solar cells. This model predicts a behavior divided in three domains for the
      electron lifetime dependence on open-circuit voltage that is in excellent
      agreement with the experimental results: a constant lifetime at high
      photovoltage, related to free electrons; an exponential increase due to internal
      trapping and detrapping and an inverted parabolla at low photovoltage that
      corresponds to the density of levels of acceptor electrolyte species, including
      the Marcus inverted region.

PMID- 15479115
TI  - Downregulation of transcription factors by ribonucleic acid interference. A novel
      approach to extend the multipotency of autologous adult stem cells?

PMID- 15479114
TI  - Human embryonic stem cell-derived fibroblastic and epitheloid lineages as xeno
      free support?

PMID- 15479116
TI  - Characterization of a mammalian smooth muscle cell line that has retained
      transcriptional and posttranscriptional potencies.
AB  - Unlike skeletal and cardiac muscle cells that differentiate irreversibly, smooth
      muscle cells (SMCs) retain a high degree of plasticity. During the so-called
      phenotypic modulation, SMCs can undergo transition between a contractile
      phenotype and a highly proliferative synthetic phenotype, as apparent from the
      extinction of numerous smooth muscle (SM) markers when they are passaged in
      culture. It would be very useful to have an SMC line that can be indefinitely
      propagated for the cellular and molecular analysis of the mechanisms that
      underlie the control of SM differentiation. This report describes an immortalized
      rabbit aorta SMC-derived cell line (U8A4) that has conserved differentiated
      properties through multiple subcultures. U8A4 cells can grow in the absence of
      serum and express the SMC markers studied, including SM alpha-actin, SM calponin,
      SM22alpha, SM alpha-tropomyosin (alpha-TM), SM myosin heavy chain (SM-MHC), and
      myocardin. U8A4 cells can activate SMC-restricted promoters like those of
      SM22alpha, SM calponin, and SM-MHC genes as efficiently as described previously
      for rat SMC lines (PAC1, A7r5, and A10). These cells can also process exogenous
      alpha-TM transcripts according to an SM-specific pattern. These results
      demonstrate that the U8A4 cell line constitutes a good alternative model to
      existing SMC lines that could facilitate the study of the transcriptional and
      posttranscriptional regulatory mechanisms underlying SMC differentiation.

PMID- 15479117
TI  - Cyclic strain stimulates proliferative capacity, alpha2 and alpha5 integrin, gene
      marker expression by human articular chondrocytes propagated on flexible silicone
      membranes.
AB  - Chondrocytes comprise less than 10% of cartilage tissue but are responsible for
      sensing and responding to mechanical stimuli imposed on the joint. However, the
      effect of mechanical signals at the cellular level is not yet fully defined. The
      purpose of this study was to test the hypothesis that mechanical stimulation in
      the form of cyclic strain modulates proliferative capacity and integrin
      expression of chondrocytes from osteoarthritic knee joints. Chondrocytes isolated
      from articular cartilage during total knee arthroplasty were propagated on
      flexible silicone membranes. The cells were subjected to cyclic strain for 24 h
      using a computer-controlled vacuum device, with replicate samples maintained
      under static conditions. Our results demonstrated increase in proliferative
      capacity of the cells subjected to cyclic strain compared with cells maintained
      under static conditions. The flexed cells also exhibited upregulation of the
      chondrocytic gene markers type II collagen and aggrecan. In addition, cyclic
      strain resulted in increased expression of the alpha2 and alpha5 integrin
      subunits, as well as an increased expression of vimentin. There was also
      intracellular reconfiguration of the enzyme protein kinase C. Our findings
      suggest that these molecules may play a role in the signal transduction pathway,
      eliciting cellular response to mechanical stimulation.

PMID- 15479118
TI  - Generation of hybrid cell lines with endothelial potential from spontaneous
      fusion of adult bone marrow cells with embryonic fibroblast feeder.
AB  - We have previously isolated mouse embryonic cell lines with endothelial potential
      using a simple empirical approach. In an attempt to isolate similar cell lines
      from adult mouse bone marrow (BM), BM cells were cultured on mitotically inactive
      mouse embryonic fibroblast (MEF) feeder cells. Several cell lines with putative
      endothelial potential were generated. They expressed endothelial-specific genes
      and formed vascular-like structures when plated on matrigel. When transplanted
      into appropriate mouse models, they incorporated into the endothelium of the
      vasculature. Similar cell lines were also obtained using human or porcine BM.
      None of these lines induced tumor formation when transplanted into
      immunodeficient Rag1-/- mice. However, all the lines were aneuploid with genetic
      markers from BM samples and the MEF feeder, suggesting that they resulted from a
      non-species-specific fusion of a BM cell and mitotically inactive MEF. Together,
      these lines demonstrated for the first time that BM cells can also undergo fusion
      with commonly used mitotically inactive feeder cells. Although these fusion cell
      lines were culture artifacts, their derivation would be useful in understanding
      fusion of BM cells with other cell types, and their endothelial potential will
      also be useful in characterizing endothelial differentiation.

PMID- 15479119
TI  - Spontaneous cell transformation: karyoplasts derived from multinucleated cells
      produce new cell growth in senescent human epithelial cell cultures.
AB  - Previously, it was shown that SV40-induced cell transformation of human diploid
      (2N), epithelial cells was a dynamic process of nuclear and cellular events. In
      this process, nuclei of polyploid (above 2N) cells broke down into multinucleated
      cells (MNCs) by amitotic division. An induced mass karyoplast (i.e., small cell
      with reduced amount of cytoplasm) budding process from the MNCs produced
      transformed cells with extended life span (EL) and altered morphology. In this
      study, without the use of SV40 and no induction of karyoplast budding, the same
      sequence of cellular events was found to occur spontaneously for the same type of
      cells at replicative senescence (no mitosis). These cell transformation events
      were followed by phase-contrast photography of living cell cultures. Primary,
      diploid, epithelial cell cultures grew for two to three passages and then entered
      senescence. Cells remaining in the cultures after widespread cell death
      (mortality stage 1; M1) developed the typical large, flat-cell morphology of
      senescence with increased cytoplasmic volume. Some of these cells were MNCs,
      mostly with two to four nuclei. Cytokinesis in MNCs and spontaneous karyoplast
      budding from MNCs were observed, and new, limited EL cell growth was present
      either in foci of cells or as prolonged cell growth over one to two passages. At
      the end of their replicative phase, the EL cells entered another death crisis
      (M2) from which no cells survived. In M2-crisis, rarely transformed cells appear
      with immortal cell growth characteristics (i.e., cell lines). Numerous examples
      of fragmentation or amitosis of polyploid nuclei in the production of
      multinucleated cells (MNCs) are presented. Such nuclear divisions produced nuclei
      with unequal sizes, which suggest unbalanced chromosomal segregations. The
      nuclear and cellular events in cell transformation are compared with a natural
      (no induction) occurrence of MNC-offspring cells in mammalian placentas. The
      possibility of a connection between these two processes is discussed. And finally
      the difference in the duration of EL cell growth from SV40-MNCs versus from
      senescent-MNCs is ascribed to increased mutational load in SV40-induced MNCs as
      compared with that in senescence MNCs.

PMID- 15479120
TI  - Effects of simulated microgravity on the development and maturation of
      dissociated cortical neurons.
AB  - Although a wealth of evidence supports the hypothesis that some functions of the
      nervous system may be altered during exposure to microgravity, the possible
      changes in basic neuronal physiology are not easy to assess. Indeed, few studies
      have examined whether microgravity affects the development of neurons in culture.
      In the present study, a suspension of dissociated cortical cells from rat embryos
      were exposed to 24 h of simulated microgravity before plating in a normal
      adherent culture system. Both preexposed and control cells were used after a
      period of 7-10 d in vitro. The vitality and the level of reactive oxygen species
      of cultures previously exposed did not differ from those of normal cultures.
      Cellular characterization by immunostaining with a specific antibody displayed
      normal neuronal phenotype in control cells, whereas pretreatment in simulated
      microgravity revealed an increase of glial fibrillary acidic protein fluorescence
      in the elongated stellate glial cells. Electrophysiological recording indicated
      that the electrical properties of neurons preexposed were comparable with those
      of controls. Overall, our results indicate that a short time of simulated
      microgravity preexposure does not affect dramatically the ability of dissociated
      neural cells to develop and differentiate in an adherent culture system.

PMID- 15479121
TI  - Cytotoxicity induced by nivalenol, deoxynivalenol, and fumonisin B1 in the SF-9
      insect cell line.
AB  - The toxicity of the mycotoxins nivalenol (NIV), deoxynivalenol (DON), and
      fumonisin B1 (FB1) was studied in the lepidopteran Spodoptera frugiperda (SF-9)
      cells, by the trypan blue dye-exclusion and 3-(4,5-dimethylthiozole-2-yl)-2,5
      biphenyl tetrazolium bromide (MTT) tests, uptake analyses of cytotoxicity, and
      cell metabolism, respectively. Deoxyribonucleic acid analysis by flow cytometry
      was used to identify apoptosis and cell cycle distribution. After 48 h of
      exposure, the MTT and trypan blue dye-exclusion tests indicated that NIV was
      significantly more toxic than DON, and both were significantly more toxic than
      FB1. The IC50 (mycotoxin concentration resulting in 50% inhibition of
      proliferation) values for NIV and DON were 4.5 and 41 microM, and the CC50
      (mycotoxin concentration that caused 50% cytotoxicity) values were 9.5 and 45
      microM, respectively. At the highest concentration of FB1 (100 microM), there was
      80% viability. With the same incubation time, cell cycle distribution showed an
      arrest of cells in the G0/G1 phase in the presence of NIV (up to 0.3 microM), DON
      (up to 3 microM), and FB1 (up to 10 microM). Morphological evidence of apoptosis
      was related to the toxicity of the substances in that the more toxic NIV induced
      late apoptosis, whereas DON and FB1 produced less-severe morphological changes
      characteristic of early apoptosis. This study suggests that NIV is more toxic
      than DON, which in turn is more toxic than FB1. These mycotoxins can modify the
      normal progression of the cell cycle and induce an apoptotic process.

PMID- 15479123
TI  - T lymphocyte therapy of cancer.
AB  - The rationale for the use of T lymphocytes to fight cancer is the immunogenicity
      of tumor cells. T cells are capable to recognize and finally to kill tumor cells.
      Adoptive cell transfer therapies provide the opportunity to overcome tolerogenic
      mechanisms by enabling the selection and activation of highly reactive T cell
      subpopulations and by manipulation of the host environment into which the T cells
      are introduced. The aim of this article is to review the possibilities,
      limitations and recent clinical experience with this novel anticancer treatment,
      namely with adoptive immunotherapy using antigen-specific T cells.

PMID- 15479122
TI  - Characterization of the human hepatocellular carcinoma (hepg2) cell line as an in
      vitro model for cadmium toxicity studies.
AB  - Biochemical indicators and in vitro models, if they mimic in vivo responses,
      offer potentially sensitive tools for inclusion in toxicity assessment programs.
      The purpose of this study was to determine whether the HepG2 cell line would
      mimic known in vivo or in vitro (or both) responses of mammalian systems when
      confronted with cadmium (Cd2+). Uptake and compartmentalization of Cd2+,
      metallothionein (MT) compartmentalization, and glutathione (GSH) depletion were
      examined. In addition, several cytotoxic and stress effects, e.g., viability
      (neutral red [NR] uptake, 3-[4,5-dimethylthiozole-2-yl]-2,5,-biphenyl tetrazolium
      bromide [MTT] dye conversion, and live/dead [L/D]), membrane damage (lactate
      dehydrogenase leakage), metabolic activity (adenosine triphosphate levels), and
      detoxification capabilities (GSH content, cytochrome P4501A1/2 [EROD
      (ethoxyresorufin-o-deethylase)] activity, and MT induction), were measured in
      both naive (no previous exposure) and Cd2+ preexposed cells. Cadmium uptake
      increased during a 24-h period. Metallothionein induction occurred in response to
      both Cd2+ and ZnCl2; however, Cd2+ was the more potent inducer. Both Cd2+ and MT
      were localized primarily in the cytoplasmic compartment. All biochemical
      responses, except EROD, showed concentration- response relationships, after 24-h
      exposure to Cd2+ (ranges 0-3 ppm [26.7 microM]). Cadmium effects were reduced in
      preexposed cells, indicating adaptive tolerance or increased resistance had
      occurred. Twenty-four-hour LC50, dose causing death of 50% of the test subjects,
      values were 0.97, 0.69, and 0.80 ppm (8.7, 6.2, and 7.2 microM) for naive cells
      and 1.45, 1.21, and 1.39 ppm (12.9, 10.7, and 12.3 microM) for preexposed cells
      based on the NR, MTT, and L/D assays, respectively. These data indicate that this
      carcinoma cell line is a useful in vitro model for cadmium toxicity studies.

PMID- 15479124
TI  - Hyperlipoproteinemia impairs endothelium-dependent vasodilation.
AB  - Atherogenic lipoproteins can cause endothelial dysfunction in the initial stage
      of atherogenesis. In our study we examined 134 patients with defined
      hyperlipoproteinemia (non-HDL cholesterol>4.1 mmol/l or triglycerides>2.5 mmol/l
      or taking any of lipid lowering drugs)--94 men and 40 women. The subgroup of
      controls of comparable age contained 54 normolipidemic individuals--30 men and 24
      women. Patients with hyperlipoproteinemia revealed significantly lower ability of
      endothelium-dependent flow-mediated vasodilation (EDV) measured on brachial
      artery (4.13+/-3.07 vs. 5.41+/-3.82 %; p=0.032) and higher carotid intima media
      thickness than normolipidemic controls (0.68+/-0.22 vs. 0.58+/-0.15 mm; p=0.005).
      In regression analysis, EDV correlated significantly with plasma concentrations
      of oxLDL (p<0.05) HDL-cholesterol (p<0.05), Apo A1 (p<0.05), ATI (p<0.01) and non
      HDL cholesterol (p<0.05). Patients with hyperlipoproteinemia showed higher plasma
      levels of oxLDL (65.77+/-9.54 vs. 56.49+/-7.80 U/l; p=0.015), malondialdehyde
      (0.89+/-0.09 vs. 0.73+/-0.08 micromol/l; p=0.010) and nitrites/nitrates (20.42+/
      4.88 vs. 16.37+/-4.44 micromol/l; p=0.018) indicating possible higher long-term
      oxidative stress in these patients.

PMID- 15479125
TI  - Gender differences in plasma levels of lipoprotein (a) in patients with
      angiographically proven coronary artery disease.
AB  - The objective of the study was to assess the association between plasma levels of
      lipoprotein(a) [Lp(a)] and the presence of angiographically defined coronary
      artery disease (aCAD). Patients (346 men and 184 women) undergoing selective
      coronary angiography (SCA) were classified into groups with positive [aCAD(+)]
      and negative [aCAD(-)] findings and their age, body mass index (BMI), waist
      circumference, blood pressure, smoking, plasma total, LDL-, HDL-cholesterol (TC,
      LDL-C, HDL-C), triglycerides (TG), apolipoprotein B (apoB), Log(TG/HDL-C) and
      TC/HDL-C were determined. Concentration of plasma Lp(a) was estimated using the
      commercial solid phase two-side immunoradiometric assay of apolipoprotein apo(a).
      The plasma Lp(a) was significantly higher in both women and men with aCAD(+)
      compared to those with aCAD(-). While there was no significant difference in the
      Lp(a) level between men and women with aCAD(-) (median 138 vs. 145 units/l), the
      women with aCAD(+) had almost twice as high Lp(a) levels as men (median 442 vs.
      274 units/l, p<0.001). Women with aCAD(+) had also significantly lower HDL
      cholesterol levels (1.09 vs. 1.20 mmol/l, p<0.05), higher triglycerides (1.82 vs.
      1.46 mmol/l, p<0.05) and Log(TG/HDL-C) than women with aCAD(-). The differences
      in Lp(a) between positive and negative findings remained highly significant
      (p<0.001 in women, p<0.05 in men) after the adjustment for age, plasma HDL- and
      LDL-cholesterol and triglycerides in logistic regression analyses. In logistic
      regression model the Lp(a) and Log(TG/HDL-C) and smoking in women but smoking and
      age in men were the most powerful predictors of positive aCAD findings. Our
      findings suggest that Lp(a) is more strongly associated with aCAD+ in women than
      in men.

PMID- 15479126
TI  - Hyperoxia attenuated nitrotyrosine concentration in the lung tissue of rats with
      experimental pneumonia.
AB  - Although nitrated proteins have been repeatedly used as markers of lung injury,
      little is known about their formation and metabolism under hyperoxia. We
      therefore measured 3-nitrotyrosine (3NTYR) concentrations in lung tissue and
      serum of rats with carrageenan-induced pneumonia exposed to hyperoxia. Twenty
      nine Wistar male rats were assigned to one of 4 groups. Two experimental groups
      were treated by intratracheal application of carrageenan (0.5 ml of 0.7 %
      solution) and then one was exposed to hyperoxia for 7 days (FIO2 0.8), the other
      to air. Rats of two control groups breathed either hyperoxic gas mixture or air
      for 7 days. At the end of exposure the ventilation was determined in
      anesthetized, intubated animals in which 3NTYR concentrations were measured in
      the lung tissue and nitrites and nitrates (NOx) were estimated in the serum.
      Carrageenan instillation increased 3NTYR concentrations in lung tissue
      (carrageenan-normoxic group 147+/-7 pmol/g protein, control 90+/-10 pmol/g
      protein) and NOx concentration in the serum (carrageenan-normoxic group 126+/-13
      ppb, control 78+/-9 ppb). Hyperoxia had no effect on lung tissue 3NTYR
      concentration in controls (control-hyperoxic 100+/-14 pmol/g protein) but blocked
      the increase of lung tissue 3NTYR in carrageenan-treated rats (carrageenan
      hyperoxic 82+/-13 pmol/g protein), increased NOx in serum (control-hyperoxic
      127+/-19 ppb) and decreased serum concentration of 3NTYR in both hyperoxic groups
      (carrageenan-hyperoxic 51+/-5 pmol/g protein, control-hyperoxic 67+/-7 pmol/g
      protein, carrageenan-normoxic 82+/-9 pmol/g protein, control 91+/-7 pmol/g
      protein). The results suggest that hyperoxia affects nitration of tyrosine
      residues, probably by increasing 3NTYR degradation.

PMID- 15479127
TI  - Effect of hyperbaric oxygen on experimental acute distal colitis.
AB  - It has been demonstrated that hyperbaric oxygen (HBO) is useful as an adjunctive
      therapy for Crohn's disease. However, its effects on ulcerative colitis have not
      been investigated. In the present study, HBO was tested for acetic acid-induced
      colitis, and antioxidant systems were evaluated to clarify its possible mode of
      action. Thirty-six Sprague-Dawley rats were randomly divided into three groups:
      sham control (Group I), colitis induced by acetic acid without any therapy (Group
      II), colitis induced by acetic acid and treated with HBO (Group III). HBO was
      given for 5 days, 2 sessions per day at 2.5-fold absolute atmosphere pressure
      (ATA) for a period of 90 min in rats in which colitis had been induced (Group
      III). Rats were sacrificed on the 5th day after the procedure. Superoxide
      dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH Px)
      activity were measured in the intestinal tissue and erythrocyte lysate. MDA and
      GSH Px were also determined in the plasma. Whereas MDA levels in erythrocyte,
      plasma and intestinal tissue were decreased, the levels of GSH Px and SOD were
      significantly increased in Group III as compared to those of Group II. The
      results of our study suggest that hyperbaric oxygen therapy has beneficial
      effects on the course of experimental distal colitis and that antioxidant systems
      may be involved in its mode of action.

PMID- 15479128
TI  - Gender differences in tumor necrosis factor alpha and leptin secretion from
      subcutaneous and visceral fat tissue.
AB  - Tumor necrosis factor alpha (TNFalpha) and leptin concentrations were determined
      in the abdominal subcutaneous and visceral (omental) adipose tissue of patients
      undergoing elective open-abdominal surgery and compared with their body mass
      index. The concentration of leptin did not differ significantly between women and
      men, being high in subcutaneous fat tissue and low in visceral fat tissue.
      TNFalpha concentration in subcutaneous fat tissue was approximately the same in
      both genders, but it was significantly lower in visceral fat tissue of women and
      unchanged in visceral fat tissue of men. A significant correlation between BMI
      and leptin was found in the two fat tissue compartments of both genders, but the
      correlation between BMI and TNFalpha was found only in subcutaneous fat tissue of
      women.

PMID- 15479129
TI  - Clozapine blocks sympathetic and thermogenic reactions induced by orexin A in
      rat.
AB  - This experiment tested the effect of clozapine on the sympathetic and thermogenic
      effects induced by orexin A. The firing rates of the sympathetic nerves to
      interscapular brown adipose tissue (IBAT), along with IBAT and colonic
      temperatures were monitored in urethane-anesthetized male Sprague-Dawley rats
      before and for 5 h after an injection of orexin A (1.5 nmol) into the lateral
      cerebral ventricle. The same procedure was carried out in rats treated with
      orexin A plus an intraperitoneal administration of clozapine (8 mg/kg bw), an
      atypical antipsychotic that is largely used in the therapy of schizophrenia. The
      same variables were monitored in rats with clozapine alone. A group of rats with
      saline injection served as control. The results show that orexin A increases the
      sympathetic firing rate, IBAT and colonic temperatures. Clozapine blocks
      completely the reactions due to orexin A. These findings suggest that clozapine
      influences strongly the thermogenic role of orexin A. Furthermore, the remarkable
      hyperthermic role played by orexin A is confirmed.

PMID- 15479131
TI  - The effect of intestinal ischemia duration on changes in plasma antioxidant
      defense status in rats.
AB  - The purpose of this study was to follow up the changes in antioxidative adaptive
      mechanisms induced by various periods of small intestinal ischemia in Wistar
      rats. The superior mesenteric artery was occluded for 15, 30, 45, 60 and 90 min.
      After the respective ischemic intervals, a reperfusion was set for 120 min.
      Samples of the serum and intestinal mucosa were taken at the end of ischemia or
      at the end of reperfusion. Total radical-trapping antioxidant parameter (TRAP) of
      the serum and the oxidative burst of neutrophils were evaluated using luminol
      enhanced chemiluminescence. Individual antioxidants in the serum and the
      concentration of thiobarbituric acid reactive substances (TBARs) in both serum
      and intestinal mucosa were measured spectrophotometrically. Increased activation
      of circulating neutrophils was found after the reperfusion irrespective of the
      duration of ischemia. TRAP of the serum was increased at the end of the ischemia
      lasting from 30 to 90 min. This effect was further enhanced by the subsequent
      reperfusion period. Ascorbate and urate contributed considerably to the TRAP
      value especially after reperfusion following 60 and 90 min of ischemia. On the
      other hand, no significant changes in albumin and bilirubin serum concentrations
      were observed. Contrary to the mobilized antioxidative mechanisms, increased
      lipid peroxidation was observed in both serum and mucosa samples.

PMID- 15479130
TI  - Regeneration of coenzyme Q9 redox state and inhibition of oxidative stress by
      Rooibos tea (Aspalathus linearis) administration in carbon tetrachloride liver
      damage.
AB  - The effect of rooibos tea (Aspalathus linearis) on liver antioxidant status and
      oxidative stress was investigated in rat model of carbon tetrachloride-induced
      liver damage. Synthetic antioxidant N-acetyl-L-cysteine (NAC) was used for
      comparison. Administration of carbon tetrachloride (CCl4) for 10 weeks decreased
      liver concentrations of reduced and oxidized forms of coenzyme Q9 (CoQ9H2 and
      CoQ9), reduced -tocopherol content and simultaneously increased the formation of
      malondialdehyde (MDA) as indicator of lipid peroxidation. Rooibos tea and NAC
      administered to CCl4-damaged rats restored liver concentrations of CoQ9H2 and
      alpha-tocopherol and inhibited the formation of MDA, all to the values comparable
      with healthy animals. Rooibos tea did not counteract the decrease in CoQ9,
      whereas NAC was able to do it. Improved regeneration of coenzyme Q9 redox state
      and inhibition of oxidative stress in CCl4-damaged livers may explain the
      beneficial effect of antioxidant therapy. Therefore, the consumption of rooibos
      tea as a rich source of natural antioxidants could be recommended as a market
      available, safe and effective hepatoprotector in patients with liver diseases.

PMID- 15479132
TI  - The protective effect of aminoguanidine on cerebral ischemic damage in the rat
      brain.
AB  - The NADPH-diaphorase (NADPH-d) histochemical technique is commonly used to
      localize the nitric oxide (NO) produced by the enzyme nitric oxide synthase (NOS)
      in neural tissue. The expression of inducible nitric oxide synthase (iNOS) is
      induced in the late stage of cerebral ischemia, and NO produced by iNOS
      contributes to the delay in recovery from brain neuronal damage. The present
      study was performed to investigate whether the increase in nitric oxide
      production via inducible nitric oxide synthase was suppressed by the
      administration of aminoguanidine, a selective iNOS inhibitor, as it follows a
      decrease of NADPH-diaphorase activity (a marker for NOS) after four-vessel
      occlusion used as an ischemic model. The administration of aminoguanidine (100
      mg/kg i.p., twice per day up to 3 days immediately after the ischemic insult)
      reduced the number of NADPH-diaphorase positive cells to control levels. Our
      results indicated that aminoguanidine suppressed NADPH-diaphorase activity, and
      also decreased the number of NADPH-diaphorase positive cells in the CA1 region of
      the hippocampus following ischemic brain injury.

PMID- 15479133
TI  - Characterization of neuromuscular transmission in mice with progressive
      motoneuronopathy.
AB  - Progressive motoneuronopathy (PMN) is an autosomal recessive mouse disease, which
      is characterized by the development of hind limbs paralysis rapidly progressing
      to the anterior parts of the body, muscular atrophy, respiratory depression, and
      death at 6-7 postnatal weeks. Here, we recorded the resting membrane potential
      (RMP), spontaneous miniature endplate potentials (MEPPs), and quantum content of
      endplate potentials (EPP) at the diaphragm muscle fibers in controls and PMN mice
      aged 18 to 43 days. In control animals, there was a progressive increase in RMP,
      MEPP frequency and EPP quantum content, as well as a decrease in mean MEPP
      amplitude. In PMN mice, the developmental increase in frequency and decrease in
      the amplitude of MEPPs was practically stopped at the postnatal day 18, whereas
      RMP increased but only until the age of 31 days and then progressively decreased.
      The distribution histogram of RMP in PMN mice older than 35 days revealed the
      existence of two subpopulations of muscle fibers: one showing a denervation-like
      decrease in RMP and the second, which was matching controls. In addition, EPP
      quantum content was significantly attenuated in older PMN animals. These results
      indicate that neurotransmission is severely affected in advanced, but not in
      early stage of disease, which is apparently due to a partial denervation of the
      muscles.

PMID- 15479134
TI  - Effects of stable adenosine receptor agonists on bone marrow hematopoietic cells
      as inferred from the cytotoxic action of 5-fluorouracil.
AB  - The aim of the study was to investigate the effects of stable adenosine receptor
      agonists on bone marrow hematopoiesis by utilizing the model of hematopoietic
      damage induced by 5-fluorouracil (5-FU), a cycle-specific cytotoxic agent.
      Effects of a non-selective agonist NECA activating all the known adenosine
      receptors (A1, A2A, A2B, A3) and of the selective agonists for A1 (CPA), A2A (CGS
      21680), and A3 (IB-MECA) adenosine receptors were investigated. Experiments were
      performed with B10CBAF1 mice under in vivo conditions. Adenosine receptor
      agonists were given in single injections before 5-FU administration and the
      effects were determined 4 days later. The numbers of femoral marrow nucleated
      cells and hematopoietic progenitor cells (CFC-GM and BFU-E) were taken as indices
      of the effects. The non-selective agonist NECA given at a dose of 200 nmol/kg
      induced biphasic time-dependent effects, i.e. protection and sensitization, when
      given 10 h and 22 h before 5-FU administration, respectively. The use of isomolar
      doses of selective receptor agonists indicated that the protective effects of
      NECA were induced by activation of A2A and A2B receptors, while the sensitizing
      action of NECA was mediated via A3 receptors. In addition, it was observed that
      A1 receptors induced protection when activated by administration of CPA 22 h
      before 5-FU. These findings are discussed with respect to the action of adenosine
      receptor agonists on the cell cycle state and on the cell cycle-independent
      cellular protective mechanisms.

PMID- 15479136
TI  - Assessment of exhaled gases in ventilated preterm infants.
AB  - Hydrogen peroxide (H2O2) production in exhaled air was measured in ventilated
      preterm newborns at 5, 24 and 48 hours after delivery, using originally designed
      method of exhaled breath condensate (EBC) collection. H2O2 production in expired
      gas was 812+/-34 pmol/20 min during the first measurement and then declined to
      389+/-21 at 24 hours and 259+/-26 pmol/20 min at 48 hours.

PMID- 15479135
TI  - Phospholipid composition of myocardium in children with normoxemic and hypoxemic
      congenital heart diseases.
AB  - Samples of myocardial tissue were obtained during cardiac surgery from children
      operated for different types of normoxemic and hypoxemic congenital heart
      diseases. The phospholipid composition was analyzed by thin layer chromatography.
      The concentration of total phospholipids (PL), phosphatidylcholine and
      phosphatidylethanolamine (PE) was found lower in atrial tissue of both normoxemic
      and hypoxemic groups in comparison with the ventricles. When comparing the
      difference between hypoxemic and normoxemic defects, hypoxemia was found to
      increase the concentration of total PL, PE and phosphatidylserine in ventricles
      and total PL and PE in the atria. The increased level of particular phospholipid
      species may represent adaptive mechanisms to hypoxemia in children with
      congenital heart diseases.

PMID- 15479137
TI  - The A-204C polymorphism in the cholesterol 7alpha-hydroxylase (CYP7A1) gene
      determines the cholesterolemia responsiveness to a high-fat diet.
AB  - The aim of the study was to ascertain whether the A-204C polymorphism in the
      cholesterol 7 -hydroxylase (CYP7A1) gene plays any role in determining LDL
      cholesterol (LDL-C) concentration responsiveness to a high-fat diet. The
      concentrations of total cholesterol and LDL-cholesterol were measured in eleven
      healthy men (age: 30.9+/-3.2 years; BMI: 24.9+/-2.7 kg/m(2);;) who were
      homozygous for either the -204A or -204C allele, after 3 weeks on a low-fat (LF)
      diet and 3 weeks on a high-fat (HF) diet. During both dietary regimens, the
      isocaloric amount of food was provided to volunteers; LF diet contained 22 % of
      energy as a fat and 2.2 mg of cholesterol/kg of body weight a day, HF diet 40 %
      of fat and 9.7 mg of cholesterol/kg of body weight a day. In six subjects
      homozygous for the -204C allele, the concentrations of cholesterol and LDL
      cholesterol were significantly higher on HF than on LF diet (cholesterol: 4.62
      vs. 4.00 mmol/l, p<0.05; LDL-C: 2.15 vs. 1.63 mmol/l, p<0.01, respectively); no
      significant change was observed in five subjects homozygous for the -204A allele.
      There were no other differences in lipid and lipoprotein-lipid concentrations.
      Therefore, the polymorphism in the cholesterol 7alpha-hydroxylase promotor region
      seems to be involved in the determination of cholesterol and LDL-C responsiveness
      to a dietary fat challenge.

PMID- 15479149
TI  - Outstanding Scientist of 2004. Joseph K. McLaughlin, PhD: A world leader in
      implant research.
AB  - OBJECTIVE: To describe the key contributions of Dr. Joseph K. McLaughlin,
      Outstanding Scientist of 2004. METHODS: We review the scientific literature and
      indicate how epidemiologic research conducted by Dr. McLaughlin has clarified
      long-term health effects among persons with breast and other medical implants.
      RESULTS: Dr. Joseph K. McLaughlin has conducted and directed more research into
      the long-term effects of human implants than any other scientist worldwide. His
      insights greatly elucidated the long-term health consequences associated with a
      variety of implanted devices, including silicone and saline breast implants, hip
      and knee replacements, temporomandibular and finger joint devices, and
      pacemakers. By initiating and bringing to fruition a series of innovative
      epidemiologic investigations, Dr. McLaughlin and his colleagues have provided the
      scientific basis for making judgments about alleged adverse health effects
      following cosmetic, reconstructive, and reparative implant surgery. CONCLUSIONS:
      Dr. McLaughlin's seminal investigations have provided reassurance that breast and
      other implants have not demonstrably increased the risk of cancer or other
      systemic diseases. The comprehensive and rigorous nature of this research merits
      his selection as Outstanding Scientist of 2004.

PMID- 15479150
TI  - Laparoscopic splenectomy--a review.
AB  - Laparoscopic splenectomy has become the standard approach in many institutions
      when splenectomy is indicated for benign hematologic disease and has gained
      acceptance in patients with malignant hematologic disease and splenomegaly. It is
      a technically difficult procedure and is associated with a steep learning curve,
      with operative times initially longer than those associated with open
      splenectomy. However, technical advancements such as hand-assisted laparoscopic
      splenectomy have facilitated increased acceptance of laparoscopy as an approach
      that is superior to open splenectomy, even in patients with malignant hematologic
      disease and/or splenomegaly. When compared to open splenectomy, laparoscopic
      splenectomy is associated with shorter postoperative hospitalization and improved
      cosmesis.

PMID- 15479151
TI  - CAPROSYN*, another major advance in synthetic monofilament absorbable suture.
AB  - CAPROSYN* suture is the latest innovation in monofilament synthetic suture. This
      suture is prepared from POLYGLYTONE*6211, a synthetic polyester composed of
      glycolide, caprolactone, trimethylene carbonate, and lactide. The purpose of this
      study was to compare the biomechanical performance of CAPROSYN* suture to that of
      CHROMIC GUT suture. The biomechanical performance studies included quantitative
      measurements of wound security, strength loss, mass loss, potentiation of
      infection, tissue drag, knot security, knot rundown, as well as suture stiffness.
      Both CAPROSYN* and CHROMIC GUT sutures provided comparable resistance to wound
      disruption. Prior to implantation, suture loops of CAPROSYN* had a significantly
      greater mean breaking strength than suture loops of CHROMIC GUT. Three weeks
      after implantation of these absorbable suture loops, the sutures had no
      appreciable strength. The rate of loss of suture mass of these two sutures was
      similar. As expected, CHROMIC GUT sutures potentiated significantly more
      infection than did the CAPROSYN* sutures. The handling properties of the
      CAPROSYN* sutures were far superior to those of the CHROMIC GUT sutures. The
      smooth surface of the CAPROSYN* sutures encountered lower drag forces than did
      the CHROMIC GUT sutures. Furthermore, it was much easier to reposition the
      CAPROSYN* knotted sutures than the knotted CHROMIC GUT sutures. In the case of
      CHROMIC GUT sutures, it was not possible to reposition a two-throw granny knot.
      These biomechanical performance studies demonstrated the superior performance of
      synthetic CAPROSYN* sutures compared to CHROMIC GUT sutures and provide
      compelling evidence of why CAPROSYN* sutures are an excellent alternative to
      CHROMIC GUT sutures.

PMID- 15479152
TI  - Saving President Reagan's life. The need for an organized emergency medical
      system in the United States to save lives of all casualties.
AB  - We are describing a heretofore untold narrative description of the emergency
      medical plan that saved the life of President Reagan on March 30th 1981. In 1976,
      Dr. Richard Edlich, director of the Emergency Medical Services at the University
      of Virginia Medical Center, wrote an editorial on the need for an emergency
      medical plan for the President of the United States. One year later Dr. Edlich
      enlisted the help of five distinguished experts in emergency medical systems in
      our nation to develop an emergency medical plan for the President of the United
      States. This published emergency medical plan was coauthored by Dr. David Boyd,
      the Director of Emergency Medical Services of the Department of Public Health and
      Welfare. Dr. Boyd wisely alerted both the Department of Health and Welfare as
      well as the White House staff, including Secret Service, of this plan. Realizing
      the importance of immediate emergency care, the Secret Service agent wisely
      recommended that the wounded President Reagan be immediately transported to the
      George Washington University Health Center, which has skilled emergency
      physicians as well as trauma surgeons, who saved the President's life. Realizing
      the benefits of this emergency medical plan that saved the life of the President
      of the United States, Drs. Edlich, Britt, and Wish will now be coordinating a
      medical narrative report that describes the development of emergency medical
      systems in the United States as well as modern trauma care in our nation.

PMID- 15479153
TI  - An overview of revolutionary advances in emergency medical care in the United
      States.
AB  - One of the goals of this manuscript is to celebrate the influential and
      productive careers of three leaders in Emergency Medical Systems: Drs. James
      Mills, R Adams Cowley, and David Boyd. Through his courageous efforts, Dr. James
      Mills established the specialty of emergency medicine, with its own educational
      training programs, credentialing process, as well as a recognized society, the
      American College of Emergency Physicians. Dr. R Adams Cowley was the preeminent
      leader in developing an organized approach in trauma care in the State of
      Maryland, with the creation of the R Adams Cowley Shock Trauma Center. Many of
      the components of his comprehensive trauma program in the State of Maryland have
      been replicated in every state in our nation. Dr. David Boyd championed the
      development of emergency medical systems throughout our nation as he served as
      Director of the Office of Emergency Medical Service Systems in the Department of
      Health, Education, and Welfare. Under the guidance of Drs. Mills, Cowley, and
      Boyd, Dr. Edlich was a leader in developing emergency medical systems in the
      Commonwealth of Virginia. Unlike the comprehensive trauma system in the State of
      Maryland, the Commonwealth of Virginia, as well as other states in our nation,
      still lack statewide helicopter aviation services that bring critically ill
      patients throughout the state from the scene of injury to separate and distinct
      trauma facilities in which life saving trauma care can be initiated without
      admission to an emergency department.

PMID- 15479154
TI  - Maryland State Police Aviation Division. A model emergency medical system for our
      nation.
AB  - This collective review has the following purposes. First we will describe each of
      the components of the Maryland State Police Aviation Division. We will then
      provide detailed information about the Atlas and Database of Air Medical Services
      (ADAMS) compiled by the center for transportation and injury research (Buffalo,
      New York) in alliance with the Association of Air Medical Services (Alexandria,
      Virginia) that provides a unique opportunity for each state to evaluate the
      comprehensive nature of their air medical services. The concept "the golden hour"
      has been molded into the world's premier public service aviation unit, which has
      proudly served the citizens of Maryland for over 24 years. This effort was
      initially made possible through a cooperative effort between the Maryland State
      Police Aviation Division and Dr. R Adams Cowley at the University of Maryland
      Hospital as a public service to the citizens of the state. This arrangement added
      a unique, economical, and life-saving component to the regionalized Emergency
      Medical Services and Critical Care system coordinated by the Maryland Institute
      for Emergency Medical Services Systems (MIESS). The Maryland State Police
      Aviation Division has four components: (1) aircraft, (2) state troopers, (3)
      system communications (SYSCOM) center, and (4) level I adult and pediatric trauma
      centers, as well as a regional burn center. ADAMS is a compilation of information
      of Air Medical Services in the United States to respond to traumas and other
      emergencies. Specifically, ADAMS provides descriptive and geographic information
      on Air Medical Service base locations, communication centers, rotor wing (RW)
      assets, and the major hospitals and transports that receive scene transports. The
      database includes all types of provider organizations including nonprofit,
      commercial, and public service (fire, police) air medical service providers, as
      well as several military units that routinely provide transport in remote areas.
      ADAMS provides national and statewide maps indicating air transport systems,
      trauma centers, and geographic population density. To provide a greater
      perspective on emergency medical care in individual states using the carefully
      tabulated ADAMS data, we compared the air emergency medical systems in Maryland
      to those of Oregon. Regardless of population density, Maryland provides air
      medical transport throughout the entire state, with the exception of only three
      small geographic areas. Maryland's 15 helicopter bases provide quick access for
      the seriously injured patient to either a Level I or pediatric trauma center
      within the "golden hour." In contrast, the air medical transportation system in
      Oregon is restricted to only three small geographic regions, making it an
      invitation to death for many seriously injured patients. It should be a federal
      mandate that the injured patient should gain access either by air transport or
      ambulance service to a Level I trauma center within that "golden hour." This
      federal legislation should include new criteria to initiate the dispatch of a
      helicopter to the scene of an accident or injury.

PMID- 15479155
TI  - Use of UV-protective windows and window films to aid in the prevention of skin
      cancer.
AB  - People are exposed to ambient solar ultraviolet (UV) radiation throughout their
      daily routine, intentionally and unintentionally. Cumulative and excessive
      exposure to UV radiation is the behavioral cause to skin cancers, skin damage,
      premature skin aging, and sun-related eye disorders. More than one million new
      cases of skin cancer were diagnosed in the United States this year. UV radiates
      directly and diffusely scattered by the various environmental and atmospheric
      conditions and has access to the skin from all directions. Because of this
      diffuse UV radiation, a person situated under a covering, such as the roof of a
      car or house, is not completely protected from the sun's rays. Because shade
      structures do not protect effectively against UV radiation, there have been major
      advances in photoprotection of glass by the development of specially designed
      photoprotective windows and films. It is the purpose of this collective review to
      highlight the photoprotective windows and films that should be incorporated into
      residential, commercial, and school glass windows to reduce sun exposure. Low
      emittence (low-E) coatings are microscopically thin, virtually invisible, metal
      or metallic oxide layers deposited on a window or skylight glazing surface to
      reduce the U-factor by suppressing radiative heat flow as well as to limit UV
      radiation. The exclusive Thermaflect coating uses the most advanced, double-layer
      soft coat technology to continue to deliver top performance for UV protection as
      well as prevent heat loss in the home. This product blocks 87% of UV radiation
      and has an Energy Star certification in all climate zones. Tints and films have
      been another important advance in glass photoprotection, especially in
      automobiles. Quality widow film products are high-tech laminates of polyester and
      metallized coatings bonded by distortion-free adhesives. The International Window
      Film Association provides members with accreditation in solar control films,
      safety films, and automotive films in an effort to increase consumer awareness
      and demand for all professionally installed film window products. The Skin Cancer
      Foundation has also played a leadership role in certifying window films that
      limit UV transmission. The Panorama Designer and Safety Films are currently
      recommended for UV photoprotection by The Skin Cancer Foundation. On the basis of
      these innovative scientific and industrial advances in window and film
      photoprotective products, we recommend that they be used in all residential,
      commercial, and school facilities to provide photoprotection in an effort to
      reduce skin cancer.

PMID- 15479156
TI  - Prelamin A endoproteolytic processing in vitro by recombinant Zmpste24.
AB  - The nuclear lamins form a karyoskeleton providing structural rigidity to the
      nucleus. One member of the lamin family, lamin A, is first synthesized as a 74
      kDa precursor, prelamin A. After the endopeptidase and methylation reactions
      which occur after farnesylation of the CAAX-box cysteine, there is a second
      endoproteolysis that occurs 15 amino acids upstream from the C-terminal
      farnesylated cysteine residue. Studies with knockout mice have implicated the
      enzyme Zmpste24 (Face-1) as a suitable candidate to perform one or both of these
      proteolytic reactions. Evidence has been presented elsewhere establishing that
      Zmpste24 possesses a zinc-dependent CAAX endopeptidase activity. In the present
      study, we confirm this CAAX endopeptidase activity with recombinant, membrane
      reconstituted Zmpste24 and show that it can accept a prelamin A farnesylated
      tetrapeptide as substrate. To monitor the second upstream endoproteolytic
      cleavage of prelamin A, we expressed a 33 kDa prelamin A C-terminal tail in
      insect cells. We demonstrate that this purified substrate possesses a C-terminal
      farnesylated and carboxyl-methylated cysteine and, therefore, constitutes a valid
      substrate for assaying the second endoproteolytic step in lamin A maturation.
      With this substrate, we demonstrate that insect cell membranes bearing
      recombinant Zmpste24 can also catalyse the second upstream endoproteolytic
      cleavage.

PMID- 15479157
TI  - The roles of Sp1, Sp3, USF1/USF2 and NRF-1 in the regulation and three
      dimensional structure of the Fragile X mental retardation gene promoter.
AB  - Expansion of a CGG.CCG-repeat tract in the 5'-untranslated region of the FMR1
      (Fragile X mental retardation 1) gene causes its aberrant transcription. This
      produces symptoms ranging from premature ovarian failure and Fragile X associated
      tremor and ataxia syndrome to FMR syndrome, depending on the size of the
      expansion. The promoter from normal alleles shows four protein-binding regions in
      vivo. We had previously shown that in mouse brain extracts two of these sites are
      bound by USF1/USF2 (upstream stimulatory factors 1 and 2) heterodimers and NRF-1
      (nuclear respiratory factor-1). We also showed that these sites are involved in
      the positive regulation of FMR1 transcription in neuronally derived cells. In the
      present study, we show that Sp1 (specificity protein 1) and Sp3 are also strong
      positive regulators of FMR1 promoter activity. We also show that, like Sp1 and E
      box-binding proteins such as USF1 and USF2, NRF-1 causes DNA bending, in this
      case producing a bend of 57 degrees towards the major groove. The combined effect
      of the four protein-induced bends on promoter geometry is the formation of a
      highly compact arch-like structure in which the 5' end of the promoter is brought
      in close proximity to the 3' end. We had previously shown that while point
      mutations in the GC-boxes decrease promoter activity, deletion of either one of
      them leads to an increase in promoter activity. We can reconcile these
      observations with the positive effect of Sp1 and Sp3 if protein-induced bending
      acts, at least in part, to bring together distally spaced factors important for
      transcription initiation.

PMID- 15479158
TI  - Steady-state kinetics and inhibition of anaerobically purified human
      homogentisate 1,2-dioxygenase.
AB  - HGO (homogentisate 1,2-dioxygenase; EC 1.13.11.5) catalyses the O2-dependent
      cleavage of HGA (homogentisate) to maleylacetoacetate in the catabolism of
      tyrosine. Anaerobic purification of heterologously expressed Fe(II)-containing
      human HGO yielded an enzyme preparation with a specific activity of 28.3+/- 0.6
      micromol x min(-1) x mg(-1) (20 mM Mes, 80 mM NaCl, pH 6.2, 25 degrees C), which
      is almost twice that of the most active preparation described to date. Moreover,
      the addition of reducing agents or other additives did not increase the specific
      activity, in contrast with previous reports. The apparent specificity of HGO for
      HGA was highest at pH 6.2 and the steady-state cleavage of HGA fit a compulsory
      order ternary-complex mechanism (K(m) value of 28.6+/-6.2 microM for HGA, K(m)
      value of 1240+/-160 microM for O2). Free HGO was subject to inactivation in the
      presence of O2 and during the steady-state cleavage of HGA. Both cases involved
      the oxidation of the active site Fe(II). 3-Cl HGA, a potential inhibitor of HGO,
      and its isosteric analogue, 3-Me HGO, were synthesized. At saturating substrate
      concentrations, HGO cleaved 3-Me and 3-Cl HGA 10 and 100 times slower than HGA
      respectively. The apparent specificity of HGO for HGA was approx. two orders of
      magnitude higher than for either 3-Me or 3-Cl HGA. Interestingly, 3-Cl HGA
      inactivated HGO only twice as rapidly as HGA. This contrasts with what has been
      observed in mechanistically related dioxygenases, which are rapidly inactivated
      by chlorinated substrate analogues, such as 3-hydroxyanthranilate dioxygenase by
      4-Cl 3-hydroxyanthranilate.

PMID- 15479159
TI  - Replication of simian virus 40 (SV40) DNA in virus-infected CV1 cells selectively
      permeabilized for small molecules by Staphylococcus aureus alpha-toxin:
      involvement of mitochondria in the fast O2-dependent regulation of SV40 DNA
      replication.
AB  - SV40 (simian virus 40)-infected CV1 cells were permeabilized with Staphylococcus
      aureus alpha-toxin for small molecules (<2 kDa) in a medium that supports DNA
      replication. Incorporation of [alpha-32P]dATP was shown to proceed at an
      essentially constant rate for at least 1 h. 32P-labelled DNA replication
      intermediates and products were analysed by alkaline sucrose density
      centrifugation. The results suggested that SV40 DNA replication in alpha-toxin
      permeabilized CV1 cells occurred essentially as in vivo. After bromodeoxyuridine
      5'-triphosphate-labelling and isopycnic banding, significant amounts of DNA
      density-labelled in both strands were detected from 110 min of permeabilization
      onwards, indicating repeated rounds of viral DNA replication in the permeabilized
      cells. Incubation of permeabilized SV40-infected cells under hypoxic culture
      conditions caused inhibition of SV40 DNA replication. As seen in unpermeabilized
      cells, SV40 DNA replication was inhibited at the stage of initiation. The
      inhibition of DNA replication induced by hypoxia was mimicked by AA (antimycin
      A), an inhibitor of mitochondrial respiration, and also by the replacement of
      glutamate, a substrate of mitochondrial respiration, by Hepes in the
      permeabilization medium. Inhibition of DNA replication was not mediated by
      intracellular ATP depletion. AA also inhibited SV40 DNA replication in
      unpermeabilized, normoxically incubated cells. Moreover, as in hypoxically
      incubated cells, the addition of glucose to SV40-infected cells incubated for
      several hours with AA induced a burst of new initiations followed by a nearly
      synchronous round of viral DNA replication. Taken together, these results
      indicate that mitochondria are involved in the oxygen-dependent regulation of
      SV40 DNA replication.

PMID- 15479160
TI  - The human SNARE protein Ykt6 mediates its own palmitoylation at C-terminal
      cysteine residues.
AB  - The yeast SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment
      protein receptor) protein Ykt6 was shown to mediate palmitoylation of the fusion
      factor Vac8 in a reaction essential for the fusion of vacuoles. Here I present
      evidence that hYkt6 (human Ykt6) has self-palmitoylating activity. Incubation of
      recombinant hYkt6 with [3H]Pal-CoA ([3H]palmitoyl-CoA) leads to covalent
      attachment of palmitate to C-terminal cysteine residues. The N-terminal domain of
      human Ykt6 contains a Pal-CoA binding site and is required for the reaction.

PMID- 15479161
TI  - Factors, fiction and endothelium-derived hyperpolarizing factor.
AB  - 1. The principal mediators of vascular tone are neural, endothelial and physical
      stimuli that result in the initiation of dilator and constrictor responses to
      facilitate the control of blood pressure. Two primary vasodilatory stimuli
      produced by the endothelium are nitric oxide (NO) and prostaglandins. An
      additional endothelium-dependent vasodilatory mechanism is characterized as the
      hyperpolarization-mediated relaxation that remains after the inhibition of the
      synthesis of NO and prostaglandins. This mechanism is due to the action of a so
      called endothelium-derived hyperpolarizing factor (EDHF) and is dependent on
      either the release of diffusible factor(s) and/or to a direct contact-mediated
      mechanism. 2. Most evidence supports the concept that 'EDHF' activity is
      dependent on contact-mediated mechanisms. This involves the transfer of an
      endothelium-derived electrical current, as an endothelium-derived
      hyperpolarization (EDH), through direct heterocellular coupling of endothelial
      cells and smooth muscle cells via myoendothelial gap junctions (MEGJ). However,
      there is a lack of consensus with regard to the nature and mechanism of action of
      EDHF/EDH (EDH(F)), which has been shown to vary within and between vascular beds,
      as well as among species, strains, sex and during development, ageing and
      disease. 3. In addition to actual heterogeneity in EDH(F), further heterogeneity
      has resulted from the less-than-optimal design, analysis and interpretation of
      data in some key papers in the EDHF literature; with such views being perpetuated
      in the subsequent literature. 4. The focus of the present brief review is to
      examine what factors are proposed as EDH(F) and highlight the correlative
      structural and functional studies from our laboratory that demonstrate an
      integral role for MEGJ in the conduction of EDH, which account for the
      heterogeneity in EDH(F), while incorporating the reported diffusible mechanisms
      in the regulation of this activity. Furthermore, in addition to the reported
      heterogeneity in the nature and mechanism of action of EDH(F), the contribution
      of experimental design and technique to this heterogeneity will be examined.

PMID- 15479162
TI  - Endothelin-1-mediated coronary vasoconstriction deteriorates myocardial
      depression in hearts isolated from lipopolysaccharide-treated rats: interaction
      with nitric oxide.
AB  - 1. The aim of the present study was to evaluate the contribution of disturbance
      of coronary perfusion to myocardial depression in hearts isolated from
      lipopolysaccharide (LPS)-treated rats and to investigate the involvement of
      endothelin (ET)-1 and nitric oxide (NO). 2. Rats were treated with LPS (10 mg/kg,
      i.p.) and, 4 h later, plasma ET-1 concentrations were measured by
      radioimmunoassay and hearts were excised for perfusion at a constant perfusion
      flow. The selective ETA receptor antagonist BQ-123, in the absence or presence of
      aminoguanidine, a specific inhibitor of inducible NO synthase, was given 15 min
      before LPS challenge. Coronary perfusion pressure (CPP) and measures of
      myocardial contractile function were recorded. 3. In hearts isolated from LPS
      treated rats, there was a marked increase in CPP that was abolished by
      pretreatment with BQ-123. In parallel, an increase in plasma ET-1 concentrations
      was seen in these rats. Lipopolysaccharide also induced decreases in left
      ventricular developed pressure (LVDP), the product of LVDP and heart rate and
      maximal rate of rise/fall of left ventricular pressure (+/- dP/dtmax). Single
      treatment with BQ-123 or aminoguanidine attenuated LPS-induced myocardial
      depression. However, when these two drugs were given simultaneously, myocardial
      depression elicited by LPS was blocked significantly. 4. Endothelin-1-mediated
      coronary vasoconstriction, together with NO, contributes to myocardial depression
      in hearts isolated from LPS-treated rats.

PMID- 15479163
TI  - Effects of caffeic acid phenethyl ester on glycerol-induced acute renal failure
      in rats.
AB  - 1. Free radicals and nitric oxide (NO) play a crucial role in the pathogenesis of
      myoglobinuric acute renal failure (ARF). The aim of the present study was to
      investigate the effects of caffeic acid phenethyl ester (CAPE), an anti-oxidant,
      on the myoglobinuric ARF induced by intramuscular hypertonic glycerol injection.
      2. Thirty rats were divided equally into three groups. Rats in group 1 were given
      saline and those in groups 2 and 3 were injected with glycerol (10 mL/kg, i.m.).
      Concomitant and 24 h after glycerol injection, CAPE (10 micromol/kg, i.p.) was
      administered to group 3 rats. Forty-eight hours after glycerol injection, blood
      samples and kidney tissues of rats were taken under anaesthesia. 3. Plasma
      concentrations of urea, creatinine, malondialdehyde (MDA) and NO were determined,
      as were superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase
      (GPx) activities and MDA levels in kidney tissues. Kidney morphology was also
      investigated. 4. In the group receiving CAPE, although SOD enzyme activity was
      found to be increased, we failed to find any protective effect of CAPE on other
      parameters investigated. Moreover, although CAPE significantly decreased NO
      levels, it increased plasma concentrations of urea and MDA. 5. We suggest that
      the effect of CAPE in decreasing NO concentrations may further increase the renal
      ischaemia in this model. Thus, CAPE may have a worsening rather than beneficial
      effect under these conditions in this model of ARF.

PMID- 15479164
TI  - Effects of inactivation of the lateral pulvinar on response properties of second
      visual area cells in Cebus monkeys.
AB  - 1. In the present study, we investigated the influence of the pulvinar nucleus
      upon response properties of single cells in the second visual area (V2) of Cebus
      monkeys. The method used consisted of the inactivation of a portion of the
      lateral pulvinar by GABA injections while studying the response properties of
      cells in V2 at the same visuotopic location as that of the inactivation. 2. After
      GABA injection in the pulvinar, most cells in V2 (67%) showed changes in
      spontaneous and/or stimulus-driven activities. Contrary to the effect found with
      inactivation of the striate cortex, which promotes a reduction in the response of
      V2 neurons, we found that the main effect of pulvinar inactivation was an
      increment in stimulus-driven responses of V2 cells (39% of units studied). A
      reduction of responses was observed in 27% of units. 3. A change in orientation
      and/or direction selectivity was found in 91% of cells after inactivation of the
      pulvinar. Most commonly, the orientation selectivity of a neuron was decreased
      during pulvinar inactivation. 4. The inactivation results indicate that the
      pulvinar projections have a modulatory effect on the activity of V2 cells.

PMID- 15479165
TI  - Implication of steady state concentrations of nitrite and nitrate metabolites of
      nitric oxide in plasma and whole blood in healthy human subjects.
AB  - 1. The aim of the present study was to determine whether the steady state NOx
      concentration reflects NOx formation in vivo. 2. A NO3- load study was performed
      after achieving NOx steady state. Chronological changes in NOx concentrations in
      plasma and whole blood samples from nine healthy subjects were determined by the
      HPLC-Griess system and NOx concentrations in erythrocytes were estimated as a
      possible NOx compartment influential in regulating plasma NOx concentrations. 3.
      Analysis was performed using the first-order one-compartment open model and the
      NOx formation rate was subsequently calculated. 4. The mean (+/-SEM) steady state
      NOx concentration of plasma (15.5 +/- 1.6 micromol/L), whole blood (12.8 +/- 1.2
      micromol/L) and erythrocytes (11.9 +/- 0.7 micromol/L) did not correlate with the
      NOx formation rate in the compartments (0.50 +/- 0.05, 0.61 +/- 0.04 and 0.91 +/-
      0.17 micromol/kg per h, respectively), whereas a significant correlation was
      found between the steady state NOx concentration and NOx elimination rate (Kel)
      in plasma (r=-0.69; P=0.04) and whole blood (r=-0.79; P=0.01). 5. Although there
      was no direct correlation between steady state NOx concentrations and serum
      creatinine levels, the correlation between half-life and serum creatinine levels
      was significant (plasma: r=0.60, P=0.02; whole blood: r=0.49, P=0.04). 6. Plasma
      NOx concentrations correlated significantly with erythrocyte NOx concentrations
      (r=0.92, P <0.01; erythrocyte NOx=0.66 x plasma NOx). 7. The results of the
      present study indicate that NOx does not accumulate excessively into erythrocytes
      at steady state and during a NO3- load and that the steady state NOx
      concentration in whole blood and plasma preferentially implies NOx elimination
      (mainly depending on renal function) rather than NOx formation.

PMID- 15479166
TI  - T393C polymorphism of GNAS1 associated with the autonomic nervous system in
      young, healthy Japanese subjects.
AB  - 1. T393C polymorphism of the gene encoding the Gs-protein alpha-subunit (GNAS1)
      has been reported recently to be associated with hypertension in which
      dysfunctions of the autonomic nervous system (ANS) are closely involved. In the
      present study, the association of this polymorphism with ANS activity was
      investigated in young, healthy Japanese males. 2. Four hundred and one subjects
      were genotyped for the T393C polymorphism of GNAS1 by polymerase chain reaction
      restriction fragment length polymorphism. Autonomic nervous system activity
      during supine rest and when standing was assessed in 137 subjects by
      electrocardiogram R-R interval power spectral analysis. 3. One hundred and fifty
      four subjects (38.4%) were homozygous for the T allele (TT), 188 (46.9%) were
      heterozygous (TC) and 59 (14.7%) were homozygous for the C allele (CC). There
      were no significant differences as to genotype among the clinical characteristics
      investigated. In power spectral analysis of heart rate variability, the high
      frequency component and parasympathetic nervous system (PNS) index during supine
      rest were significantly lower in TT and TC carriers than in CC carriers.
      Furthermore, the increase in heart rate and the responsiveness of sympathetic
      nervous system index and PNS index to postural change from supine rest to
      standing were significantly lower in TT and TC carriers than in CC carriers. 4.
      These observations suggest that the GNAS1 T393C polymorphism is associated with
      ANS activity in youth, so that it may be useful as a genetic marker for future
      pathogenesis of hypertension. Follow-up studies are necessary to clarify the
      prevalence rates of hypertension among 393T allele carriers in the present study.

PMID- 15479167
TI  - Gene expression profiles in response to the activation of adrenoceptors in A7r5
      aortic smooth muscle cells.
AB  - 1. Vascular adrenoceptors play an important role in vascular physiology and
      pathophysiology, such as hypertension, atherosclerosis and restenosis after
      angioplasty. To define the changes in the ene expression in vascular smooth
      muscle cells in response to the activation of alpha1- or beta-adrenoceptors, a
      DNA microarray was used. 2. First, the existence of alpha1- and beta
      adrenoceptors in A7r5 aortic smooth muscle cells was confirmed by radioligand
      binding. Then, the inhibitory effects of phenylephrine (an alpha1-adrenoceptor
      agonist) and isoproterenol (a beta-adrenoceptor agonist) on the proliferation of
      A7r5 cells were determined by [3H]-thymidine incorporation. 3. The A7r5 cells
      were treated with 10 micromol/L phenylephrine or 1 micromol/L isoproterenol for
      24 h and changes in gene expression were detected with the DNA microarray. Only
      14 and 20 genes were identified after treatment of cells with phenylephrine and
      isoproterenol, respectively, and most genes displayed decreased expression. The
      changed genes could be grouped into five major functional categories: cell
      signalling/communication, cell structure/motility, cell/organism defence,
      gene/protein expression and metabolism. The gene expression profile in response
      to the activation of alpha1-adrenoceptors was very different from that following
      activation of beta-adrenoceptors. Interestingly, many phenylephrine-responsive
      genes were associated with metabolism, whereas many isoproterenol-responsive
      genes encoded cell signalling and structure proteins. This means that
      adrenoceptors may modulate multiple aspects of biological function in vascular
      smooth muscle cells. 4. Collectively, the activation of both alpha1-adrenoceptors
      (with phenylephrine) and beta-adrenoceptors (with isoproterenol) inhibited the
      proliferation of A7r5 cells, but microarray data revealed that the mechanisms may
      be different: the activation of alpha1-adrenoceptors could induce the expression
      of metabolic genes, resulting in the inhibition of proliferation, whereas
      activation of beta-adrenoceptors altered the expression of genes that encoded
      cell signalling and structure proteins to inhibit cell proliferation.

PMID- 15479168
TI  - Antinociception induced by stimulating the anterior pretectal nucleus in two
      models of pain in rats.
AB  - 1. This study examined whether different parts of the rat anterior pretectal
      nucleus (APtN) may be involved in the spinal control of brief (tail flick test)
      or persistent (surgical incision of the plantar aspect of a hind paw) noxious
      inputs via activation of descending pathways. 2. We have confirmed that
      stimulation of the dorsal APtN produces a strong antinociceptive effect in the
      tail flick test, as opposed to a very weak effect obtained from the ventral APtN.
      Stimulation at the ventral APtN was the most effective part of the nucleus
      against a persistent incisional pain. 3. The incisional pain was significantly
      increased following injection of 1 or 2% lignocaine (0.25 microL) into the
      nucleus, but the effect was more intense after neural block of the ventral rather
      than the dorsal APtN. Injection of 2% lignocaine (0.10 microL) into the ventral,
      but not dorsal, APtN significantly increased the perception of the incisional
      pain. 4. We conclude that the effect of stimulating the APtN depends on the site
      of stimulation and model of pain used. Sustained noxious stimuli activate
      pathways from the ventral APtN to reduce further noxious spinal inputs. The
      noxious stimulation produced during the tail flick test may be not enough to
      activate the same circuitry, but electrical stimulation at the dorsal APtN is
      very effective in inhibiting brief thermal noxious inputs at the spinal level.

PMID- 15479169
TI  - Efficacy of bofu-tsusho-san, an oriental herbal medicine, in obese Japanese women
      with impaired glucose tolerance.
AB  - 1. In the present study, we conducted the first randomized, double-blind, placebo
      controlled study of bofu-tsusho-san (BF), an oriental herbal medicine (24 mg/day
      ephedrine in Ephedrae Herba and an efficacy equivalent of 280 mg caffeine,
      judging from the phosphodiesterase-inhibitory effect of Glycyrrhizae Radix,
      Forsythiae Fructus and Schizonepetae Spica and another 14 crude drugs) in obese
      women with impaired glucose tolerance (IGT). 2. The aim of the present study was
      to determine whether BF was effective in decreasing visceral adiposity and
      insulin resistance. Eighty-one Japanese women (body mass index (BMI) 36.5 +/- 4.8
      kg/m2) with IGT and insulin resistance (IR), who had been treated with a low
      calorie diet (5016 kj/day: 1200 kcal) and an exercise regimen (1254 kj/day: 300
      kcal), were randomized to receive either placebo (n=40) or BF treatment (n=41)
      three times a day. 3. After 24 weeks treatment, the BF group lost significantly
      (P <0.01) more bodyweight and abdominal visceral fat without a decrease in the
      adjusted resting metabolic rate (RMR), whereas the placebo group lost bodyweight
      (P <0.05) and had no significant change in abdominal visceral fat. The BF group
      had a lower fasting serum insulin level (P <0.05), a lower insulin area under the
      curve (P <0.05) and a lower level of the homeostasis model assessment of insulin
      resistance (P <0.01) compared with values before treatment. 4. We conclude that
      BF could be a useful herbal medicine in treating obesity with IGT.

PMID- 15479170
TI  - Effect of Anoectochilus formosanus on fibrosis and regeneration of the liver in
      rats.
AB  - 1. The present study examined the effects of an aqueous extract of Anoectochilus
      formosanus (AFE) on both hepatic fibrosis and regeneration in rats. 2. Fibrosis
      was induced by intraperitoneal injection of dimethylnitrosamine (DMN) for 3
      consecutive days per week for 4 weeks. 3. In DMN-treated rats, liver cirrhosis
      associated complications, such as liver atrophy, low concentrations of serum
      albumin and the accumulation of hepatic collagen, were observed. The AFE
      protected the liver against DMN-induced fibrosis, as determined by morphological
      and biochemical observations. 4. In addition, AFE was administered to two-thirds
      hepatectomized normal and DMN-injured rats. Three and 5 days after hepatectomy,
      AFE increased the extent of liver weight regeneration and the number of S-phase
      cells in DMN-injured rats, but not in normal rats. 5. These results show that AFE
      seems to be useful in the repair of liver injury, improvement of fibrotic changes
      and promotion of liver regeneration.

PMID- 15479171
TI  - Different roles of alpha1-adrenoceptor subtypes in mediating cardiomyocyte
      protein synthesis in neonatal rats.
AB  - 1. Three different alpha1-adrenoceptor subtypes, designated alpha1A, alpha1B and
      alpha1D, have been cloned and identified pharmacologically in cardiomyocytes. In
      vitro studies have suggested that alpha1-adrenoceptors play an important role in
      facilitating cardiac hypertrophy. However, it remains controversial as to which
      subtype of alpha1-adrenoceptors is involved in this response. In the present
      study, we investigated the different role of each alpha1-adrenoceptor subtype in
      mediating cardiomyocyte protein synthesis, which is a most important
      characteristic of cardiac hypertrophy in cultured neonatal rat cardiomyocytes. 2.
      Cardiomyocyte hypertrophy was monitored by the following characteristic
      phenotypic changes: (i) an increase in protein synthesis; (ii) an increase in
      total protein content; and (iii) an increase in cardiomyocyte size. 3. The role
      of each alpha1-adrenoceptor subtype in mediating cardiomyocyte protein synthesis
      was investigated by the effect of specific alpha1-adrenoceptor subtype-selective
      antagonists on noradrenaline-induced [3H]-leucine incorporation. In addition, pKB
      values for alpha1-adrenoceptor subtype-selective antagonists were calculated and
      compared with the corresponding pKi values to further identify their effects. 4.
      Activation of alpha1-adrenoceptors by phenylephrine or noradrenaline in the
      presence of propranolol significantly increased [3H]-leucine incorporation,
      protein content and cell size. 5. Pre-incubating cardiomyocytes with 5-methyl
      urapidil, RS 17053 or WB 4101 significantly inhibited noradrenaline-induced [3H]
      leucine incorporation. However, there was no effect when cardiomyocytes were pre
      incubated with BMY 7378. The correlation coefficients between pKB values for
      alpha1-adrenoceptor subtype-selective antagonists and pKi values obtained from
      cloned alpha1A-, alpha1B- or alpha1D-adrenoceptors were 0.92 (P <0.01), 0.66 (P
      >0.05) and 0.24 (P >0.05), respectively. 6. Our results suggest that the alpha1
      adrenoceptor is dominantly responsible for adrenergic hypertrophy of cultured
      cardiomyocytes in neonatal rats. The efficiency in mediating cardiomyocyte
      protein synthesis is alpha1A > alpha1B >> alpha1D.

PMID- 15479172
TI  - Interactions of tachykinin receptor antagonists with lipopolysaccharide-induced
      airway inflammation in mice.
AB  - 1. Several observations suggest that tachykinins are involved in the pathogenesis
      of bronchopulmonary alterations. We have investigated the effect of antagonists
      for tachykinin NK1 (SR 140333), NK2 (SR 48968) or NK3 (SR 142801) receptors on
      inflammatory cell recruitment, tumour necrosis factor (TNF)-alpha and interleukin
      (IL)-6 release and matrix metalloproteinase (MMP)-9 activity in the
      bronchoalveolar lavage fluid (BALF) of mice exposed to lipopolysaccharide (LPS;
      100 microg/mL aerosol for 30 min). 2. Treatment of mice with a combination of SR
      140333 and SR 48968 (10(-6) mol/L, aerosol) significantly reduced the increase in
      the number of total cells and neutrophils and MMP-9 activity in the BALF of mice
      2.5 h after LPS exposure. Treatment with the NK3 antagonist SR 142801 (10(-6)
      mol/L, aerosol) did not inhibit the influx of neutrophils, but markedly reduced
      the increase in TNF-alpha and IL-6 levels at 2.5 h and MMP-9 activity at 20 h. 3.
      These results show that the three tachykinin receptor antagonists may interfere
      with the development of airway inflammation, namely neutrophilia, TNF-alpha
      release or MMP-9 activity in the BALF of mice exposed to LPS and suggest that not
      only NK1 and NK2 receptors, but also NK3 receptors are involved in the modulation
      of the inflammatory response and airway remodelling.

PMID- 15479173
TI  - Endothelial potassium channels, endothelium-dependent hyperpolarization and the
      regulation of vascular tone in health and disease.
AB  - 1. The elusive nature of endothelium-derived hyperpolarizing factor (EDHF) has
      hampered detailed study of the ionic mechanisms that underlie the EDHF
      hyperpolarization and relaxation. Most studies have relied on a pharmacological
      approach in which interpretations of results can be confounded by limited
      specificity of action of the drugs used. Nevertheless, small-, intermediate- and
      large-conductance Ca2+-activated K+ channels (SKCa, IKCa and BKCa, respectively)
      have been implicated, with inward rectifier K+ channels (KIR) and Na+/K+-ATPase
      also suggested by some studies. 2. Endothelium-dependent membrane currents
      recorded using single-electrode voltage-clamp from electrically short lengths of
      arterioles in which the smooth muscle and endothelial cells remained in their
      normal functional relationship have provided useful insights into the mechanisms
      mediating EDHF. Charybdotoxin (ChTx) or apamin reduced, whereas apamin plus ChTx
      abolished, the EDHF current. The ChTx- and apamin-sensitive currents both
      reversed near the expected K+ equilibrium potential, were weakly outwardly
      rectifying and displayed little, if any, time- or voltage-dependent gating, thus
      having the biophysical and pharmacological characteristics of IKCa and SKCa
      channels, respectively. 3. The IKCa and SKCa channels occur in abundance in
      endothelial cells and their activation results in EDHF-like hyperpolarization of
      these cells. There is little evidence for a significant number of these channels
      in healthy, contractile vascular smooth muscle cells. 4. In a number of blood
      vessels in which EDHF occurs, the endothelial and smooth muscle cells are coupled
      electrically via myoendothelial gap junctions. In contrast, in the adult rat
      femoral artery, in which the smooth muscle and endothelial layers are not coupled
      electrically, EDHF does not occur, even though acetylcholine evokes
      hyperpolarization in the endothelial cells. 5. In vivo studies indicate that EDHF
      contributes little to basal conductance of the vasculature, but it contributes
      appreciably to evoked increases in conductance. 6. Endothelium-derived
      hyperpolarizing factor responses are diminished in some diseases, including
      hypertension, pre-eclampsia and some models of diabetes. 7. The most economical
      explanation for EDHF in vitro and in vivo in small vessels is that it arises from
      the activation of IKCa and SKCa channels in endothelial cells. The resulting
      endothelial hyperpolarization spreads via myoendothelial gap junctions to result
      in the EDHF-attributed hyperpolarization and relaxation of the smooth muscle.

PMID- 15479174
TI  - Changes in endothelium-derived hyperpolarizing factor in hypertension and ageing:
      response to chronic treatment with renin-angiotensin system inhibitors.
AB  - 1. Endothelial function is impaired in hypertension and ageing and this may be
      associated with an increase in cardiovascular disease. Several clinical studies
      have shown that blocking the renin-angiotensin system (RAS) improves endothelial
      function not only in hypertensive patients, but also in normotensive patients
      with cardiovascular disease. 2. The aim of the present study was to test whether
      endothelium-derived hyperpolarizing factor (EDHF)-mediated smooth muscle
      hyperpolarization and relaxation are altered in hypertension and ageing and, if
      so, whether chronic treatment with RAS inhibitors (the angiotensin-converting
      enzyme inhibitor enalapril and the angiotensin AT1 receptor antagonist
      candesartan) would correct such changes. 3. Endothelium-derived hyperpolarizing
      factor-mediated responses were examined in mesenteric arteries from 12-month-old
      spontaneously hypertensive rats (SHR) and 3-, 6-, 12- and 24-month-old
      normotensive Wistar-Kyoto (WKY) rats. Furthermore, both strains were treated for
      3 months with either RAS blockers or a conventional therapy with hydralazine and
      hydrochlorothiazide from 9 to 12 months of age. 4. In arteries of 12-month-old
      SHR, EDHF-mediated responses were impaired compared with age-matched WKY rats. In
      SHR, all antihypertensive treatments improved the impairment of EDHF-mediated
      responses; however, RAS inhibitors tended to improve these responses to a greater
      extent compared with conventional therapy with hydralazine and
      hydrochlorothiazide. 5. In arteries of WKY rats, EDHF-mediated responses were
      impaired at the age of 12 and 24 months compared with 3- and 6-month-old rats,
      with the response tending to be impaired to a greater extent in 24-month-old
      rats. 6. Three months of treatment of WKY rats, until 12 months of age, with RAS
      inhibitors, but not with conventional therapy with hydralazine and
      hydrochlorothiazide, improved the age-related impairment of EDHF-mediated
      responses, despite a similar reduction in blood pressure by both treatments. 7.
      These findings suggest that: (i) EDHF-mediated hyperpolarization and relaxation
      decline with hypertension and ageing in rat mesenteric arteries; (ii)
      antihypertensive treatment restores the impaired EDHF-mediated responses in
      hypertension; (iii) RAS inhibitors may be more efficacious in improving
      endothelial dysfunction associated with hypertension; and (iv) chronic treatment
      with RAS inhibitors improves the age-related impairment of EDHF-mediated
      responses, presumably through the blockade of RAS but not blood pressure lowering
      alone.

PMID- 15479177
TI  - Notice of retraction of article.

PMID- 15479178
TI  - Changes in renal medullary volume account for the relationship between arterial
      pressure and renal medullary interstitial cell lipid granule content.

PMID- 15479179
TI  - Hutchinson-Gilford progeria syndrome.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder
      that causes premature, rapid aging shortly after birth. Recently, de novo point
      mutations in the Lmna gene have been found in individuals with HGPS. Lmna encodes
      lamin A and C, the A-type lamins, which are an important structural component of
      the nuclear envelope. The most common HGPS mutation is located at codon 608
      (G608G). This mutation creates a cryptic splice site within exon 11, which
      deletes a proteolytic cleavage site within the expressed mutant lamin A.
      Incomplete processing of prelamin A results in nuclear lamina abnormalities that
      can be observed in immunofluorescent studies of HGPS cells. Mouse models, such as
      Lmna knockout, Zmpste24 knockout, and Lmna L530P knockin will help the study of
      progeria. Lmna mutations have also recently been found in patients with atypical
      forms of progeria. The discovery of the HGPS mutations brings the total number of
      diseases caused by mutant Lmna to nine, underscoring the astonishing spectrum of
      laminopathies. Future research into HGPS could also provide important clues about
      the general process of aging and aging-related diseases.

PMID- 15479180
TI  - Progress in searching for susceptibility loci and genes for smoking-related
      behaviour.
AB  - Smoking behaviour is influenced by both genetic and environmental factors. Many
      years of twin and adoption studies have demonstrated that heritability is at
      least 50% responsible for both smoking initiation and smoking persistence.
      Furthermore, the extent, to which genetic and environmental factors contribute to
      smoking behaviour, is significantly different in men and women. Linkage analyses
      from several independent studies provide evidences for suggested linkage of
      smoking behaviour to chromosomes 1, 2, 4, 5, 6, 9, 10, 11, 14, 17, 18 and 21.
      However, almost none of these loci have been replicated yet. Furthermore,
      numerous population-based association studies have been performed to examine the
      effects of a number of candidate genes, such as cytochrome P450, dopamine
      receptor (DR) and transporter, serotonin transporter and nicotinic acetylcholine
      receptor, on smoking behaviour. However, many of these reports have not yet
      received independent confirmation. Of these candidate genes, the D2 dopamine
      receptor (DRD2) gene has been extensively studied. Meta-analysis of 12 reported
      studies showed a significantly higher prevalence of the DRD2 TaqI A1 allele in
      smokers than that in non-smokers (p < 0.0001; pooled OR = 1.50; 95% CI = 1.33
      1.70). For other candidate genes, insufficient published studies are available to
      allow a meta-analysis to be performed, or meta-analysis showed no significant
      difference between smokers and non-smokers. More studies are necessary to
      determine whether these genes play a significant role in smoking behaviour.

PMID- 15479184
TI  - Growing bone knowledge.
AB  - Molecular dissection of genetic bone diseases continues to deliver exciting
      insights on developmental control of skeletal patterning and growth. But will
      diagnostic tests become available to the genetic community on a wide basis?

PMID- 15479185
TI  - Exploration of the impact of messages about genes and race on lay attitudes.
AB  - The effect of messages about genetics on lay audiences was assessed through an
      experimental study that exposed participants (n = 96) to a Public Service
      Announcement about race, genes, and heart disease. Participants who received a
      message that specified either 'Whites' or 'Blacks' as the subject of the message
      demonstrated elevated levels of racism, genetic basis for racism, and one
      dimension of genetic discrimination as compared to those receiving a version of
      the message with no race specification or in a no-message control condition. The
      presentation of such messages to the public is not recommended until additional
      research clarifies this finding and perhaps describes mitigating vocabularies or
      approaches.

PMID- 15479186
TI  - Haplotypic analyses of the aldosterone synthase gene CYP11B2 associated with
      stage-2 hypertension in northern Han Chinese.
AB  - The objective of this study was to investigate the association of polymorphisms
      in the aldosterone synthase gene CYP11B2 (-344T/C, Lys173/Arg, and an intronic
      conversion [IC]) with stage-2 hypertension in northern Han Chinese. A total of
      503 hypertensives and their age-, gender-, and area-matched controls were
      included in this study. The female hypertensives had significantly higher
      frequencies of the -344T, 173Lys, and IC-conversion alleles (p = 0.002, 0.002,
      and 0.014, respectively). The estimated frequency of haplotype composed of the 
      344T, 173Lys, and IC-conversion alleles (haplotype 4) was significantly higher in
      the female hypertensives compared with their controls (p = 0.007). Using a
      multivariate score test, we found that haplotype 4 remained associated with
      female hypertension after the adjustment for covariates (p = 0.003), while the
      haplotype 3 of T-Arg-WT showed a protective effect both in the males and in the
      females (p = 0.03 and 0.006, respectively). The odds ratio for haplotype phase of
      4-4 was 2.60 (95% CI, 1.21-5.58) and for 3-3, 0.20 (95% CI, 0.03-0.77). These
      results indicate that the Lys173 and the IC-conversion allele of the CYP11B2 gene
      confer an increased risk for stage-2 hypertension in northern Han Chinese women.

PMID- 15479187
TI  - A_16_C haplotype in the FcepsilonRIbeta gene confers a higher risk for atopic
      asthma in the Indian population.
AB  - We conducted a case-control study aimed at identifying polymorphisms and
      haplotypes in the FcepsilonRIbeta gene associated with asthma and its associated
      phenotypes such as serum IgE levels. A G/A polymorphism in intron 2, a (CA)n
      repeat polymorphism in intron 5, and a C/T polymorphism in 3'-UTR, encompassing a
      length of 8.74 Kb, were genotyped, and haplotypes were generated for unrelated
      patients and healthy volunteers in two independent cohorts. A significant
      association was observed at the level of alleles and genotypes studied with
      asthma independently in the two cohorts (p < 0.05). A change in CC_AA genotype
      combination to a non-CC_AA genotype was associated with reduced risk for asthma.
      Interestingly, a three-locus haplotype, A_16_C, was found to be significantly
      associated with asthma (p = 10(-5) in cohort A and p = 0.004 in cohort B). On the
      other hand, the haplotype G_18_T was found to be negatively associated with
      asthma (p = 0.007 in cohort A and p = 0.0004 in cohort B). This is the first
      study identifying a haplotype A_16_C that predisposes individuals to asthma in
      the Indian population.

PMID- 15479188
TI  - The clinical evaluation and pregnancy outcome of euploid fetuses with increased
      nuchal translucency.
AB  - This review aims to address the systematic work-up and counseling throughout
      pregnancies with increased nuchal translucency (NT) in euploid fetuses. Original
      articles from peer-reviewed English-language journals between 1997 and 2003 were
      studied. They all included descriptions of pregnancy outcomes of euploid fetuses
      with increased NT. Eleven studies reporting on the pregnancy outcome of 2128
      euploid fetuses with increased NT (> or = 3 mm or > or = 95 centile) were
      retrieved by our literature search. A statistical analysis was conducted for
      assessing the consistency of effects across studies. The chi2 tests were applied
      to verify the homogeneity of the results from different series. A significant
      difference was found between the studies even when the results were analyzed
      separately according to various NT cutoff levels (i.e. > or = 3 mm, > or = 3.5-4
      mm, and > or = 95 centile). These discrepancies suggest that those studies are
      significantly different and therefore, cannot be combined for meta-analysis. Of
      all the reported series, 2.2-10.6% of the fetuses have miscarried and 0.5-15.8%
      ended in perinatal death. There was an overall rate of 0.5-12.7%
      neurodevelopmental problems, and 2.1-7.6% of the malformations which were
      undiagnosed before birth. Importantly, 70-90% fetuses had normal outcomes. A
      detailed two-step anomaly scan including midgestation fetal echocardiography
      should be part of perinatal management of pregnancies with increased fetal NT.
      Data on relevant family history and persistence of nuchal edema provide
      additional relevant information for planning pregnancy management.

PMID- 15479189
TI  - Anticipated reactions to genetic testing for hereditary non-polyposis colorectal
      cancer susceptibility.
AB  - Genetic testing for cancer susceptibility (e.g. hereditary non-polyposis
      colorectal cancer) is available for some families with a history of colon cancer.
      Our aim was to investigate participants' anticipated emotional and behavioral
      reactions to genetic testing for colon cancer and whether gender or clinical risk
      influences these reactions. 437 asymptomatic participants with a colorectal
      cancer family history completed a questionnaire about anticipated emotions and
      actions, under different genetic testing scenarios. More women than men
      anticipated feeling worried, regretful, and angry if tested positive. People at
      lower-risk anticipated more surprise and disbelief than those at higher-risk.
      People anticipated feeling more guilt, regret and less relief if they were not
      tested than if they were. High-risk results were anticipated to increase
      depression and worry. Most people still wanted screening if at low risk,
      anticipated leading healthier lifestyles whatever the result, but would make more
      plans for the future if they were at high risk. Clinical implications are that as
      anticipated emotional effects of not being tested may be more severe than having
      a test, people choosing to forgo testing should feel able to reconsider their
      decision anytime. Most people did not anticipate strong emotional reactions but
      thought it would change their lifestyle and would like continued clinical
      surveillance whatever the result.

PMID- 15479190
TI  - Attitudes and beliefs concerning prostate cancer genetic screening.
AB  - This quantitative study determines the values, beliefs, and attitudes influencing
      the intention of men to undergo or defer genetic testing for prostate cancer risk
      using a model based on components of the Theory of Reasoned Action and Health
      Belief Model. Telephone interviews of a community sample of 400 men in a large,
      East Coast metropolitan area of diverse educational, ethnic, and age backgrounds
      were conducted to rank key values and beliefs about genetic testing for prostate
      cancer risk in anticipation of its future availability. Descriptive statistics,
      univariate analyses, and logistic regression were used in data analysis. The
      factors of values attached to consequences, motivation from self, beliefs in
      benefits, and a motivation to comply with others (borderline) were statistically
      significant for testing intention. Of all demographics, only increased education
      was associated with diminished interest in testing. Desire to be tested varied
      widely across groups of men. Based on these identified values, health
      professionals can better understand men's values and beliefs on the risks and
      benefits of testing. The relationship of men to others, family and society,
      require further investigation in this and other aspects of genetic testing.

PMID- 15479191
TI  - High prevalence of V37I genetic variant in the connexin-26 (GJB2) gene among non
      syndromic hearing-impaired and control Thai individuals.
AB  - Hearing loss is highly prevalent with a worldwide incidence of 1-2 per 1000
      newborns. Several previous studies have demonstrated that mutations of connexin
      26 (Cx26 or GJB2) are responsible for most cases of the recessive non-syndromic
      sensorineural hearing loss (NSSHL). Certain mutations have been described
      frequently among various populations, which include 35delG, 167delT, and 235delC.
      Recently, a missense mutation, V37I, was reported as a pathogenic change in East
      Asian affected individuals. To identify genetic variants associated with NSSHL in
      Thai population, we performed mutation analysis of Cx26 in 166 unrelated probands
      with NSSHL and 205 controls. We identified seven novel genetic variants in Cx26.
      We also identified a high prevalence of the V37I mutation among both affected
      probands (11.1%) and control subjects (8.5%), which suggests that the pathologic
      role of V37I may be modified by other genes. Our data support previous studies
      that show heterogeneity in the frequencies and types of mutations in Cx26 within
      populations and among ethnicities and that before clinical significance and
      causality can be attributed to a genetic variant, functional characterization is
      necessary.

PMID- 15479192
TI  - SDHB, SDHC, and SDHD mutation screen in sporadic and familial head and neck
      paragangliomas.
AB  - Mutations within three genes, SDHB, SDHC, and SDHD, encoding distinct subunits of
      a hetero-oligomeric protein known as the mitochondrial complex II, a component of
      the mitochondrial electron transport chain and the Krebs cycle have been
      implicated in the pathogenesis of hereditary paraganglioma (PGL). This study
      describes a mutation screen of SDHB, SDHC, and SDHD in blood and tumor samples of
      14 sporadic and three familial cases of head and neck PGL (HNP). Germline
      mutations in SDHB and SDHD were identified in two of the three affected
      individuals with familial HNP. The SDHB mutation was a novel 3 base pair, in
      frame deletion of AGC at nucleotide 583-585 encoding serine (delS195). The SDHD
      mutation was a C to T transition within codon 81 causing substitution of proline
      with leucine (P81L). In contrast to familial cases, no germline or somatic
      mutations were identified in the 14 sporadic cases of HNP. The presence of
      mutations within SDHB and SDHD in two of the three samples of familial PGLs and
      absence of mutations in sporadic cases is consistent with the significant
      contribution of these genes to familial but not sporadic PGL. The etiology of
      sporadic PGL remains to be elucidated.

PMID- 15479193
TI  - C283Y gamma-sarcoglycan gene mutation in the Bulgarian Roma (Gypsy) population:
      prevalence study and carrier screening in a high-risk community.
AB  - Limb-girdle muscular dystrophy type 2C (LGMD2C) is caused by mutations in the
      gamma-sarcoglycan gene where a founder Gypsy mutation C283Y was detected. The
      Bulgarian Gypsy LGMD2C patients, as the Gypsy patients from other countries, were
      found to be homozygous for this mutation. Considering the large number of Gypsies
      in Bulgaria and the high percent of consanguinity and endogamy a raised carrier
      frequency of the C283Y mutation was expected especially in North-Eastern Bulgaria
      where most of the patients originate from. Here, we present the precise
      geographic distribution of the C283Y mutation in the general Roma population from
      the whole Bulgarian territory by determining the carrier frequency of the
      mutation in dry blood newborn samples. Our results show that the geographic
      distribution of this founder mutation and the disease are not geographically
      restricted only among Gypsies from North-Eastern Bulgaria. We stress upon the
      regions with detected high carrier and/or disease frequency and upon the results
      from the performed carrier screening on volunteers in one of these regions. The
      ongoing carrier-screening programs in isolated Gypsy groups would be of a great
      benefit for the genetic prophylaxis of the disease. Such regions should be with
      priority in the Bulgarian healthcare system for performing a carrier-screening
      program.

PMID- 15479194
TI  - Familial colloid cysts of the third ventricle.
AB  - A father and daughter with colloid cysts of the third ventricle are described.
      The nine previously reported examples of familial occurrence are reviewed, and
      the conclusion is reached that inheritance is likely autosomal dominant. The
      proportion of all cases which are genetic is not known. A plea is made for
      routine detailed and thorough family histories on all patients with such cysts
      and a high index of suspicion for non-specific symptoms in relatives such as
      headaches, migraine, depression, anxiety, nausea and vomiting.

PMID- 15479195
TI  - 'Secrets and lies'--the difficulties of communicating within families with
      inherited cancer syndromes.

PMID- 15479196
TI  - Identification of five novel BOR mutations in human EYA1 gene associated with
      branchio-oto-renal syndrome by a DHPLC-based assay.

PMID- 15479197
TI  - Epigenetic defects, assisted reproductive technology, and clinical practice: a
      call for clinicians and genetic counselors.

PMID- 15479199
TI  - Frequency of contact allergy in German children and adolescents patch tested
      between 1995 and 2002: results from the Information Network of Departments of
      Dermatology and the German Contact Dermatitis Research Group.
AB  - Allergic contact dermatitis (ACD) affects approximately 7% of the general
      population. To evaluate the frequency of ACD in children, we analysed patch test
      results collected by the Information Network of Departments of Dermatology
      between 1995 and 2002. Data of 285 children (6-12 year) and 2175 adolescent
      patients (13-18 year) were analysed to determine the frequency of sensitization
      to the 30 most common contact allergens, adjusting for age and sex. As control
      group, we defined adult patients (60-66 year, n = 7904). The top allergens in
      children were thimerosal, gentamicin sulphate, nickel-II-sulphate, ammoniated
      mercury, cobalt-II-chloride, fragrance mix, bufexamac, Compositae mix, propylene
      glycol and turpentine. The overall proportion of sensitized patients according to
      the patch test results was 52.6% in the children group compared to 49.7% in the
      adolescent group. These findings were similar in the adult group at 52.2%. The
      detailed analysis regarding sex, occupation, atopy, site of eczema and age showed
      distinct patterns in each group indicating age-specific exposures. Atopy-related
      diseases were more common in children compared to adults. On the basis of the
      data of this study, the relationship between atopy and the risk of development of
      ACD, at least in children, needs further investigation.

PMID- 15479198
TI  - Sesquiterpene lactone mix patch testing supplemented with dandelion extract in
      patients with allergic contact dermatitis, atopic dermatitis and non-allergic
      chronic inflammatory skin diseases.
AB  - We investigated the value of patch testing with dandelion (Compositae) extract in
      addition to sesquiterpene lactone (SL) mix in selected patients. After we
      detected a case of contact erythema multiforme after patch testing with dandelion
      and common chickweed (Caryophyllaceae), additional testing with common chickweed
      extract was performed. A total of 235 adults with a mean age of 52.3 years were
      tested. There were 66 men and 169 women: 53 consecutive patients with allergic
      contact dermatitis (ACD); 43 with atopic dermatitis (AD); 90 non-atopics
      suffering from non-allergic chronic inflammatory skin diseases; 49 healthy
      volunteers. All were tested with SL mix 0.1% petrolatum (pet.) and diethyl ether
      extracts from Taraxacum officinale (dandelion) 0.1 and 3.0% pet. and from
      Stellaria media (common chickweed) 0.1 and 3% pet. A total of 14 individuals
      (5.9%) showed allergic reaction (AR) to at least 1 of the plant allergens, 4
      (28.6%) to common chickweed extract, and 11 (78.6%) to Compositae allergens.
      These 11 persons made the overall prevalence of 4.7%: 8 (3.4%) were SL-positive
      and 3 (1.3%) reacted to dandelion extract. 5 persons (45.5%) had AD, 2 had ACD, 2
      had psoriasis and 2 were healthy controls. The Compositae allergy was relevant in
      8 cases (72.7%). The highest frequency of SL mix sensitivity (9.3%) was among
      those with AD. Half the SL mix-sensitive individuals had AD. ARs to dandelion
      extract were obtained only among patients with eczema. A total of 9 irritant
      reactions (IRs) in 9 individuals (3.8%) were recorded, 8 to SL mix and 1 to
      common chickweed extract 3.0% pet. No IR was recorded to dandelion extract (P =
      0.007). Among those with relevant Compositae allergy, 50.0% had AR to fragrance
      mix and balsam of Peru (Myroxylon pereirae resin) and colophonium. SLs were
      detected in dandelion but not in common chickweed. Our study confirmed the
      importance of 1 positive reaction for emerging, not fully established, Compositae
      allergy. In conclusion, the overall prevalence of 4.7% in our study represents a
      basal SL mix detection rate of 3.4% reinforced and safely supplemented by testing
      with the dandelion extract.

PMID- 15479200
TI  - Patch test results with the metalworking fluid series of the German Contact
      Dermatitis Research Group (DKG).
AB  - Based on the information of the interdisciplinary task force on allergy
      diagnostics in the metal branch, in 2001, the German Contact Dermatitis Research
      Group (DKG) compiled two metalworking fluid (MWF) test series with currently and
      previously used components, respectively. After 2 years of patch testing, we
      present results obtained with these series, based on data of the Information
      Network of Departments of Dermatology (IVDK). 251 metalworkers who were patch
      tested because of suspected MWF dermatitis in 2002 and 2003 were included in this
      retrospective data analysis. Of these, 206 were tested with the current MWF
      series and 155 with the historical MWF series. Among the current MWF allergens,
      monoethanolamine ranked 1st with 11.6% positive reactions. Diethanolamine (3.0%),
      triethanolamine (1.1%), and diglycolamine (1.9%) elicited positive reactions far
      less frequently. Allergic reactions to p-aminoazobenzene were frequently observed
      (6.0%), but the relevance of these reactions is still obscure. Positive reactions
      to biocides ranged from 4.5% for Bioban CS 1135 to 0.5% for iodopropynyl
      butylcarbamate and 2-phenoxyethanol. Concomitant reactions to formaldehyde, which
      caused positive reactions in 3.3%, and formaldehyde releasers occurred to varying
      extents without conclusive pattern. No positive reactions were seen to dibutyl
      phthalate, di-2-ethylhexyl phthalate, tricresyl phosphate, isopropyl myristate or
      benzotriazole. With the historical MWF test series, positive reactions to
      methyldibromo glutaronitrile (MDBGN) were observed most frequently. However,
      sensitization via allergen sources other than MWF seems likely, as MDBGN, during
      the study period, has been one of the most frequent preservative allergens in
      cosmetics and body care products. Other historical MWF allergens comprised
      morpholinyl mercaptobenzothiazole (3.3%), benzisothiazolinone (BIT; 2.0%) and
      Bioban P 1487(1.3%). BIT is currently used in MWF again, so it was shifted to the
      current MWF test series. As decreasing reaction frequencies to former MWF
      allergens that are no longer used can be expected, the historical series should
      be re-evaluated after some years. The test series with current MWF allergens has
      to be kept up-to-date based on information from industry and to be kept concise
      by eliminating test substances which never cause positive reactions.

PMID- 15479201
TI  - Characteristics of wet work in the cleaning industry.
AB  - Wet work is the main cause of occupational contact dermatitis in the cleaning
      industry. Dermatologists and occupational physicians need to base their primary
      and secondary prevention for workers in the cleaning industry on the
      characteristics of wet work exposures. We quantified the burden of wet work in
      professional office cleaning activities with a continuous standardized
      observation by trained observers of 41 office cleaners. Duration and frequency of
      wet work exposure and of different cleaning activities were assessed. Wet work
      made up 50% of such cleaning work. Within a typical 3-hr shift, a mean frequency
      of 68 episodes of wet work was observed, which classifies office cleaning as wet
      work. Skin exposure to irritants was markedly different among cleaners who did
      the same cleaning activities. Reduction in skin irritation can be achieved by
      training the workers. Because this group of workers, who have a low level of
      education, has a high risk of developing irritant hand dermatitis, a special
      effort on training and instruction should be made. A reduction of exposure can be
      achieved by: using gloves more often; using gloves for a shorter period of time;
      using gloves while doing activities that otherwise cause the skin to be in
      contact with water and cleaning substances and washing hands with water only,
      reserving soap for when the hands are visibly dirty.

PMID- 15479202
TI  - Skin protection in nursing work: promoting the use of gloves and hand alcohol.
AB  - Nursing has been identified as a wet-work occupation, with a high prevalence of
      occupational irritant contact dermatitis. Reduction of exposure to skin irritants
      contributes to the prevention of occupational skin disease in nurses. The role of
      the use of soap and water, hand alcohol and gloves in prevention programmes is
      discussed. 2 additional measures for reducing exposure to skin irritants are
      postulated: use of hand alcohol instead of soap and water in disinfection
      procedures when the hands are not visibly dirty; use of gloves in wet activities
      such as patient washing to prevent the hands from becoming wet and visibly dirty.
      We investigated the effectiveness of these recommendations in a model. Mean daily
      wet-work exposure during nursing work was modelled: regular model. We also
      modelled exposure to skin irritants in combination with the implementation of
      these recommendations: prevention model. The hands of healthy volunteers were
      exposed to the regular or the prevention model over 3 weeks for 5 days a week.
      The change in transepidermal water loss (TEWL) on the back of the hands was
      measured after 3 weeks of exposure to these wet-work simulations. An increase in
      TEWL occurred with the regular model, while mean TEWL decreased in the prevention
      model. Skin irritation from occlusion by gloves appeared to be more pronounced in
      the regular model compared to the prevention model. The results of this study
      justify the conclusion that in nursing work, hand alcohol is the preferred
      disinfectant. Although the prevention model implies increased occlusive exposure,
      this has no additional irritant effect, probably because of the absence of soap
      exposure.

PMID- 15479203
TI  - Reactivity to patch tests with nickel sulfate and fragrance mix in infants.
AB  - The pattern of patch test reactivity to nickel sulfate and fragrance mix was
      studied with respect to patch test performance, reproducibility and clinical
      relevance in a population of unselected infants followed prospectively from birth
      to 18 months of age. TRUE Testtrade mark patches with nickel sulfate in 3
      concentrations, 200, 66 and 22 microg/cm(2), and fragrance mix 430 microg/cm(2)
      were used. A likely case of nickel sensitivity was defined as a reproducible
      positive reaction with at least homogeneous erythema and palpable infiltration
      occurring at least 2x and present at both the 12 and 18 months follow-up. 543
      infants (268 girls and 275 boys) were tested at least 1x, 304 were tested at both
      12 and 18 months. The prevalence of a reproducible positive reaction to nickel
      was 8.6% (20 girls and 6 boys). A transient positive reaction was observed in 111
      children. Clinical relevance of nickel sensitivity was found in only 1 child. No
      reproducible positive reaction to fragrance mix was found. The high proportion of
      transient patch test reactivity to nickel sulfate 200 microg/cm(2) indicates that
      this standard concentration used for adults cannot be applied to infants. The
      interpretation of a single positive nickel patch test in infants must be assessed
      with caution and it is probably of non-specific or irritant nature.

PMID- 15479204
TI  - Allergic contact dermatitis from dyes in wigs following diphencyprone treatment.

PMID- 15479205
TI  - Type IV hypersensitivity to sodium metabisulfite in local anaesthetic.

PMID- 15479206
TI  - Delayed-type hypersensitivity to the ultra-low-molecular-weight heparin
      fondaparinux.

PMID- 15479207
TI  - Metal allergy to implanted orthopaedic prosthesis after postoperative
      Staphylococcus aureus infection.

PMID- 15479208
TI  - Occupational airborne allergic contact dermatitis from azithromycin.

PMID- 15479209
TI  - Type I and Type IV allergy to unfractionated heparin and low-molecular-weight
      heparin with no reaction to recombinant hirudin.

PMID- 15479210
TI  - Occupational allergic contact dermatitis from 1,6-bis (2,3-epoxypropoxy)
      naphthalene in a one-component epoxy coating.

PMID- 15479211
TI  - Contact allergy to thiuram in a musician.

PMID- 15479212
TI  - Allergic contact dermatitis in 191 consecutively patch tested children.

PMID- 15479213
TI  - Occupational allergic contact dermatitis from champignon and Polish mushroom.

PMID- 15479214
TI  - Occupational facial allergic contact dermatitis caused by Finnish pine and spruce
      wood dusts.

PMID- 15479215
TI  - ACE inhibitors and cardiovascular protection in diabetes.

PMID- 15479216
TI  - Effects of dietary fatty acids on insulin sensitivity and secretion.
AB  - Globalization and global market have contributed to increased consumption of high
      fat, energy-dense diets, particularly rich in saturated fatty acids( SFAs).
      Polyunsaturated fatty acids (PUFAs) regulate fuel partitioning within the cells
      by inducing their own oxidation through the reduction of lipogenic gene
      expression and the enhancement of the expression of those genes controlling lipid
      oxidation and thermogenesis. Moreover, PUFAs prevent insulin resistance by
      increasing membrane fluidity and GLUT4 transport. In contrast, SFAs are stored in
      non-adipocyte cells as triglycerides (TG) leading to cellular damage as a
      sequence of their lipotoxicity. Triglyceride accumulation in skeletal muscle
      cells (IMTG) derives from increased FA uptake coupled with deficient FA
      oxidation. High levels of circulating FAs enhance the expression of FA
      translocase the FA transport proteins within the myocites. The biochemical
      mechanisms responsible for lower fatty acid oxidation involve reduced carnitine
      palmitoyl transferase (CPT) activity, as a likely consequence of increased
      intracellular concentrations of malonyl-CoA; reduced glycogen synthase activity;
      and impairment of insulin signalling and glucose transport. The depletion of IMTG
      depots is strictly associated with an improvement of insulin sensitivity, via a
      reduced acetyl-CoA carboxylase (ACC) mRNA expression and an increased GLUT4
      expression and pyruvate dehydrogenase (PDH) activity. In pancreatic islets, TG
      accumulation causes impairment of insulin secretion. In rat models, beta-cell
      dysfunction is related to increased triacylglycerol content in islets, increased
      production of nitric oxide, ceramide synthesis and beta-cell apoptosis. The
      decreased insulin gene promoter activity and binding of the pancreas-duodenum
      homeobox-1 (PDX-1) transcription factor to the insulin gene seem to mediate TG
      effect in islets. In humans, acute and prolonged effects of FAs on glucose
      stimulated insulin secretion have been widely investigated as well as the effect
      of high-fat diets on insulin sensitivity and secretion and on the development of
      type 2 diabetes.

PMID- 15479217
TI  - Gliclazide modified release: results of a 2-year study in patients with type 2
      diabetes.
AB  - AIM: To evaluate the efficacy and safety of gliclazide modified release (MR),
      alone or combined with other oral antidiabetic drug(s) over 2 years in type 2
      diabetic patients. METHODS: Two consecutive periods: (i) a 10-month, double-blind
      comparative study, where 800 type 2 diabetic patients were randomized either to
      gliclazide MR (30-120 mg) once daily or to gliclazide (80-320 mg) twice daily.
      All the patients were then treated with gliclazide MR for a 2-month switch
      period; (ii) 549 patients were subsequently enrolled in a 12-month, open-label
      period on gliclazide MR alone or in combination according to glycaemic control,
      507 of whom completed the study. RESULTS: Glycated haemoglobin (HbA1c)
      significantly decreased from baseline over 2 years by -0.46 +/- 1.08% in the
      whole cohort of 2-year completed patients, -0.95% in the subgroup of diet-failed
      patients and by -0.34% in the subgroup of patients pretreated with one oral
      antidiabetic drug. HbA1c was reduced by -0.43 +/- 1.02% and by -0.51 +/- 1.16%,
      when gliclazide MR was used in monotherapy and in combination therapy,
      respectively. The overall incidence of symptoms suggestive of hypoglycaemia was
      4.8 episodes/100 patient-year, with no severe episode. This incidence was
      similarly low in elderly patients and patients with impaired renal function.
      CONCLUSION: Gliclazide MR alone or in combination with another oral antidiabetic
      drug significantly improved glycaemic control in type 2 diabetic patients over 2
      years with a very good safety profile, notably in the elderly and in patients
      with impaired renal function.

PMID- 15479218
TI  - Role of early insulin secretion in postglucose-loading hyperglycaemia and postfat
      loading hyperlipidaemia: comparing nateglinide and glibenclamide for acute
      effects on insulin secretion in OLETF rats.
AB  - AIM: The aim of this study was to clarify the role of an early insulin secretion
      in postprandial hyperglycaemia and hyperlipidaemia; a study using spontaneously
      type 2 diabetic Otsuka Long-Evans Tokushima Fatty rats with visceral obesity was
      performed to investigate the acute effect of nateglinide (NAT) vs. glibenclamide
      (GB) on increases in glucose after glucose loading and on increases in
      triglyceride (TG) after fat loading. METHODS: Fasting rats were given 50 mg/kg of
      NAT, 1 mg/kg of GB or 5% methyl cellulose (vehicle) as control and then
      immediately given oral glucose 1 g/kg. RESULTS: An acute increase in insulin
      levels in portal blood peaked at 15 min in the NAT group, while insulin levels in
      the GB group continued to increase significantly after 60 min. Glucose levels in
      peripheral blood were significantly lower in the NAT group at 30 and 60 min and
      in the GB group at 120, 180 and 270 min after glucose loading, compared with
      those in the vehicle group. Subsequently, fasting rats were given NAT, GB or
      vehicle and then immediately given oral fat emulsion (soy oil 2 g/kg). An acute
      increase in insulin secretion was seen with NAT, peaking at 30 min, while TG,
      chylomicron and very low-density lipoprotein levels after fat loading were shown
      to be significantly lower with NAT than with vehicle. However, the continued
      insulin secretion observed with GB led to no significant decrease in TG levels
      after fat loading. In addition, lipoprotein lipase mRNA expression in adipose
      tissue increased significantly 120 min after NAT administration in comparison
      with baseline. This increase was not noted with GB administration. CONCLUSION:
      Abnormalities in early insulin secretion are closely associated with the
      pathogenesis of various disease conditions that combine to characterize type 2
      diabetes, suggesting that normalizing early insulin response in portal blood
      represents an important treatment not only for postprandial hyperglycaemia but
      also for postprandial hyperlipidaemia.

PMID- 15479219
TI  - High glucose mediates pro-oxidant and antioxidant enzyme activities in coronary
      endothelial cells.
AB  - AIM: Excess levels of free radicals such as nitric oxide (NO) and superoxide
      anion (O(2)(-)) are associated with the pathogenesis of endothelial cell
      dysfunction in diabetes mellitus. This study was designed to investigate the
      underlying causes of oxidative stress in coronary microvascular endothelial cells
      (CMECs) exposed to hyperglycaemia. METHODS: CMECs were cultured under normal (5.5
      mmol/l) or high glucose (22 mmol/l) concentrations for 7 days. The activity and
      expression (protein level) of endothelial NO synthase (eNOS), inducible NOS
      (iNOS), NAD(p)H oxidase and antioxidant enzymes, namely, superoxide dismutase
      (SOD), catalase and glutathione peroxidase (GPx) were investigated by specific
      activity assays and Western analyses, respectively, while the effects of
      hyperglycaemia on nitrite and O(2)(-) generation were investigated by Griess
      reaction and cytochrome C reduction assay, respectively. RESULTS: Hyperglycaemia
      did not alter eNOS or iNOS protein expressions and overall nitrite generation, an
      index of NO production. However, it significantly reduced the levels of
      intracellular antioxidant glutathione by 50% (p < 0.05) and increased the protein
      expressions and activities of p22-phox, a membrane-bound component of pro-oxidant
      NAD(p)H oxidase and antioxidant enzymes (p < 0.05). Free radical scavengers,
      namely, Tiron and mercaptopropionylglycine (MPG) (0.1-1 micromol/l) reduced
      hyperglycaemia-induced antioxidant enzyme activity and increased glutathione and
      nitrite generation to the levels observed in CMEC cultured in normoglycaemic
      medium (p < 0.01). The differences in enzyme activity and expressions were
      independent of the increased osmolarity generated by high glucose levels as
      investigated by using equimolar concentrations of mannitol in parallel
      experiments. CONCLUSIONS: These results suggest that hyperglycaemia-induced
      oxidative stress may arise in CMEC as a result of enhanced pro-oxidant enzyme
      activity and diminished generation of antioxidant glutathione. By increasing the
      antioxidant enzyme capacity, CMEC may protect themselves against free radical
      induced cell damage in diabetic conditions.

PMID- 15479220
TI  - Antioxidant vitamins C and E ameliorate hyperglycaemia-induced oxidative stress
      in coronary endothelial cells.
AB  - OBJECTIVE: Vitamins C and E have protective features in many disease states
      associated with enhanced oxidative stress. The aim of this study was to
      investigate whether vitamin(s) C and/or E modulate hyperglycaemia-induced
      oxidative stress by regulating enzymatic activities of prooxidant, i.e. NAD(P)H
      oxidase and/or antioxidant enzymes, namely endothelial nitric oxide synthase
      (eNOS), superoxide dismutase, catalase and glutathione peroxidase, using coronary
      microvascular endothelial cells (CMEC). METHODS: CMEC were cultured under normal
      (5.5 mM) or high glucose (22 mM) concentrations for 7 days. The enzyme activities
      were determined by specific assays. The levels of O(2) (-) and nitrite were
      measured by cytochrome c reduction and Griess assays respectively. RESULTS:
      Hyperglycaemia did not alter eNOS activity or overall nitrite generation, an
      index of NO production. However, it increased NAD(P)H oxidase and antioxidant
      enzyme activities (p < 0.05). Specific inhibitors of NAD(P)H oxidase, i.e.
      phenylarsine oxide (0.1-3 microm) and 4-(2-aminoethyl)benzenesulfonyl fluoride (5
      100 microm) and vitamins C and E (0.1-1 microm) significantly reduced prooxidant
      and antioxidant enzyme activities in CMEC exposed to hyperglycaemia (p < 0.01).
      The differences in enzyme activities were independent of increases in osmolarity
      generated by high glucose levels as investigated by using equimolar
      concentrations of mannitol in parallel experiments. CONCLUSIONS: Vitamins C and E
      may protect CMEC against hyperglycaemia-induced oxidative stress by concomitantly
      regulating prooxidant and antioxidant enzyme activities.

PMID- 15479221
TI  - Variants in the human beta 1-, beta 2-, and beta 3-adrenergic receptor genes are
      not associated with morbid obesity in children and adolescents.
AB  - AIM: beta-adrenergic receptors (beta-ARs) are of key importance for the
      regulation of lipolysis and thermogenesis by catecholamines. Genetic defects in
      expression or function of beta(1)- beta(2)- and/or beta(3)-AR could affect energy
      homeostasis and predispose an individual towards the development of obesity. We
      therefore investigated the possible association of polymorphisms in the beta
      adrenergic receptor genes with early onset obesity. METHODS: Frequencies of the
      following variants were assessed in extremely obese children and healthy
      underweight controls: Gly/Ser in codon 49 and Arg/Gly in codon 389 of the beta(1)
      AR, Arg/Gly in codon 16 and Gln/Glu in codon 27 of the beta(2)-AR, Trp/Arg in
      codon 64 of the beta(3)-AR. RESULTS: The Ser49 allele in the beta(1)-AR gene was
      found at a frequency of 0.131 in obese and 0.136 in lean subjects (p = 0.835),
      while the Gly389 allele in the beta(1)-AR had a frequency of 0.319 in obese and
      0.328 in lean subjects (p = 0.802). Gly16 in the beta(2)-AR was found with a
      frequency of 0.590 in obese and 0.611 in lean subjects (p = 0.591) and the Glu27
      allele in the beta(2)-AR had a frequency of 0.380 in obese and 0.420 in lean
      subjects (p = 0.298). CONCLUSION: We did not detect significant differences for
      allele and carrier frequencies of individual polymorphisms. Together with
      previously obtained data on genotype distribution of a beta(3)-AR variant in the
      same study group, no significant differences were found between obese and lean
      subjects for the distribution of individuals with variants in none, one, two or
      all three beta-ARs. Our data make it unlikely that polymorphisms in beta-ARs are
      involved in the pathogenesis of early onset obesity.

PMID- 15479222
TI  - Clinical markers for the identification of metabolically healthy but obese
      individuals.

PMID- 15479223
TI  - HCA efficiency.

PMID- 15479226
TI  - A kinetic study of sugarcane sucrose synthase.
AB  - The kinetic data on sugarcane (Saccharum spp. hybrids) sucrose synthase (SuSy,
      UDP-glucose: D-fructose 2-alpha-D-glucosyltransferase, EC 2.4.1.13) are limited.
      We characterized kinetically a SuSy activity partially purified from sugarcane
      variety N19 leaf roll tissue. Primary plot analysis and product inhibition
      studies showed that a compulsory order ternary complex mechanism is followed,
      with UDP binding first and UDP-glucose dissociating last from the enzyme. Product
      inhibition studies showed that UDP-glucose is a competitive inhibitor with
      respect to UDP and a mixed inhibitor with respect to sucrose. Fructose is a mixed
      inhibitor with regard to both sucrose and UDP. Kinetic constants are as follows:
      Km values (mm, +/- SE) were, for sucrose, 35.9 +/- 2.3; for UDP, 0.00191 +/-
      0.00019; for UDP-glucose, 0.234 +/- 0.025 and for fructose, 6.49 +/- 0.61. values
      were, for sucrose, 227 mm; for UDP, 0.086 mm; for UDP-glucose, 0.104; and for
      fructose, 2.23 mm. Replacing estimated kinetic parameters of SuSy in a kinetic
      model of sucrose accumulation with experimentally determined parameters of the
      partially purified isoform had significant effects on model outputs, with a 41%
      increase in sucrose concentration and 7.5-fold reduction in fructose the most
      notable. Of the metabolites included in the model, fructose concentration was
      most affected by changes in SuSy activity: doubling and halving of SuSy activity
      reduced and increased the steady-state fructose concentration by about 42 and
      140%, respectively. It is concluded that different isoforms of SuSy could have
      significant differential effects on metabolite concentrations in vivo, therefore
      impacting on metabolic regulation.

PMID- 15479227
TI  - Yeast glycogenin (Glg2p) produced in Escherichia coli is simultaneously
      glucosylated at two vicinal tyrosine residues but results in a reduced bacterial
      glycogen accumulation.
AB  - Saccharomyces cerevisiae possesses two glycogenin isoforms (designated as Glg1p
      and Glg2p) that both contain a conserved tyrosine residue, Tyr232. However, Glg2p
      possesses an additional tyrosine residue, Tyr230 and therefore two potential
      autoglucosylation sites. Glucosylation of Glg2p was studied using both matrix
      assisted laser desorption ionization and electrospray quadrupole time of flight
      mass spectrometry. Glg2p, carrying a C-terminal (His6) tag, was produced in
      Escherichia coli and purified. By tryptic digestion and reversed phase
      chromatography a peptide (residues 219-246 of the complete Glg2p sequence) was
      isolated that contained 4-25 glucosyl residues. Following incubation of Glg2p
      with UDPglucose, more than 36 glucosyl residues were covalently bound to this
      peptide. Using a combination of cyanogen bromide cleavage of the protein
      backbone, enzymatic hydrolysis of glycosidic bonds and reversed phase
      chromatography, mono- and diglucosylated peptides having the sequence PNYGYQSSPAM
      were generated. MS/MS spectra revealed that glucosyl residues were attached to
      both Tyr232 and Tyr230 within the same peptide. The formation of the highly
      glucosylated eukaryotic Glg2p did not favour the bacterial glycogen accumulation.
      Under various experimental conditions Glg2p-producing cells accumulated
      approximately 30% less glycogen than a control transformed with a Glg2p lacking
      plasmid. The size distribution of the glycogen and extractable activities of
      several glycogen-related enzymes were essentially unchanged. As revealed by high
      performance anion exchange chromatography, the intracellular maltooligosaccharide
      pattern of the bacterial cells expressing the functional eukaryotic transgene was
      significantly altered. Thus, the eukaryotic glycogenin appears to be incompatible
      with the bacterial initiation of glycogen biosynthesis.

PMID- 15479228
TI  - Cytokinin oxidase/dehydrogenase genes in barley and wheat: cloning and
      heterologous expression.
AB  - The cloning of two novel genes that encode cytokinin oxidase/dehydrogenase (CKX)
      in barley is described in this work. Transformation of both genes into
      Arabidopsis and tobacco showed that at least one of the genes codes for a
      functional enzyme, as its expression caused a cytokinin-deficient phenotype in
      the heterologous host plants. Additional cloning of two gene fragments, and an in
      silico search in the public expressed sequence tag clone databases, revealed the
      presence of at least 13 more members of the CKX gene family in barley and wheat.
      The expression of three selected barley genes was analyzed by RT-PCR and found to
      be organ-specific with peak expression in mature kernels. One barley CKX (HvCKX2)
      was characterized in detail after heterologous expression in tobacco.
      Interestingly, this enzyme shows a pH optimum at 4.5 and a preference for
      cytokinin ribosides as substrates, which may indicate its vacuolar targeting.
      Different substrate specificities, and the pH profiles of cytokinin-degrading
      enzymes extracted from different barley tissues, are also presented.

PMID- 15479229
TI  - Expression of the Drosophila melanogaster ATP synthase alpha subunit gene is
      regulated by a transcriptional element containing GAF and Adf-1 binding sites.
AB  - Mitochondrial biogenesis is a complex and highly regulated process that requires
      the controlled expression of hundreds of genes encoded in two separated genomes,
      namely the nuclear and mitochondrial genomes. To identify regulatory proteins
      involved in the transcriptional control of key nuclear-encoded mitochondrial
      genes, we have performed a detailed analysis of the promoter region of the alpha
      subunit of the Drosophila melanogaster F1F0 ATP synthase complex. Using transient
      transfection assays, we have identified a 56 bp cis-acting proximal regulatory
      region that contains binding sites for the GAGA factor and the alcohol
      dehydrogenase distal factor 1. In vitro mutagenesis revealed that both sites are
      functional, and phylogenetic footprinting showed that they are conserved in other
      Drosophila species and in Anopheles gambiae. The 56 bp region has regulatory
      enhancer properties and strongly activates heterologous promoters in an
      orientation-independent manner. In addition, Northern blot and RT-PCR analysis
      identified two alpha-F1-ATPase mRNAs that differ in the length of the 3'
      untranslated region due to the selection of alternative polyadenylation sites.

PMID- 15479230
TI  - Characterization of a cathepsin L-associated protein in Artemia and its
      relationship to the FAS-I family of cell adhesion proteins.
AB  - We reported previously that the major cysteine protease in embryos and larvae of
      the brine shrimp, Artemia franciscana, is a heterodimeric protein consisting of a
      catalytic subunit (28.5 kDa) with a high degree of homology with cathepsin L, and
      a noncatalytic subunit (31.5 kDa) of unknown function. In the study reported here
      the noncatalytic subunit, or cathepsin L-associated protein (CLAP), was separated
      from cathepsin L by chromatography on Mono S and found to contain multiple
      isoforms with pIs ranging from 5.9 to 6.1. Heterodimeric and monomeric cathepsin
      L showed similar activity between pH 5 and 6.5, while the heterodimer was about
      twice as active as monomeric cathepsin L below pH 5. The heterodimer was more
      stable than the monomer between pH 6 and 7.4 and at 30-50 degrees C. Artemia CLAP
      and cathepsin L are present in nearly equimolar amounts at all stages in the life
      cycle and most abundant in encysted eggs and embyros. Moreover, CLAP, either free
      or as a complex with cathepsin L, was resistant to hydrolysis by cathepsin L. Two
      clones coding for CLAP were isolated from an Artemia embryo cDNA library and
      sequenced. Both clones have nearly identical open reading frames, but show
      differences at the 5'- and 3'-termini. Each cDNA clone has an extensive 3'
      untranslated region containing 70-72% A+T. The deduced amino acid sequence of
      CLAP cDNA revealed two domains which were very similar to domains in fasciclin I
      and other cell adhesion proteins. The nucleotide sequences of clones 1 and 2 have
      been entered into the NCBI database (AY307377 and AY462276). This study supports
      the view that the noncatalytic subunit of the heterodimeric cysteine protease in
      Artemia stabilizes cathepsin L at various pH and temperatures normally
      inconsistent with cathepsin L from other organisms, and that CLAP serves as a
      docking mechanism for cathepsin L at nonlysosomal sites in Artemia embryos.

PMID- 15479231
TI  - Investigation of the contribution of histidine 119 to the conduction of protons
      through human Nox2.
AB  - The conduction of protons through human Nox2 has previously been shown to be
      dependent upon His115. Alignment of sequences for both animal and plant Nox
      proteins indicated that histidines 115 and 119 are both highly conserved, while
      His111 was conserved among animal homologues of Nox1-4. To investigate the
      possible role that these histidine residues might play in the conduction of
      protons through Nox2, we have introduced both paired and single mutations into
      these histidine residues. Each construct was used to generate a CHO cell line in
      which the expression of the mutated Nox2 was assessed. Nox2 was expressed in each
      of the CHO cell lines generated, however, the level of expression of H111/115L in
      CHO cells was lower and that of H111L very much reduced, compared to that of wild
      type Nox2. The arachidonic acid activated proton flux was absent in the CHO cell
      lines expressing the mutations of H111/115L, H111/119L or H115/119L, compared to
      that observed for wild-type Nox2. Similarly only a small efflux of protons was
      observed from CHO cells expressing either H119L or H111L. In all cases the
      expected proton flux was elicited through the addition of the protonophore,
      carbonyl cyanide m-chlorophenylhydrazone. Conclusions regarding the role of
      His111 in the conduction of protons cannot be drawn due to the reduced
      expression. We can, however, conclude that His119, in addition to His115, is
      required for the conduction of protons through Nox2. His119 has been identified
      as a highly conserved residue for which no function has previously been proposed.

PMID- 15479232
TI  - Factors affecting habituation of PC12 cells to ATP.
AB  - Extracellular ATP triggers catecholamine secretion from PC12 cells by activating
      ionotropic purine receptors. Repeated stimulation by ATP leads to habituation of
      the secretory response. In this paper, we use amperometric detection to monitor
      the habituation of PC12 cells to multiple stimulations of ATP or its agonist.
      Cells habituate to 30 microm ATP slower than they do to 300 or 600 microm ATP.
      Modifying external Mg2+ affects the response of cells to 30 microm ATP, but does
      not affect habituation, suggesting that habituation does not necessarily
      correspond to either stimulus intensity or cellular response. Mg2+ affects the
      initial response of PC12 cells to 2MeSATP in a manner similar to ATP. Increasing
      external [Mg2+] to 3.0 mm, however, eliminates habituation to 2MeSATP. This
      habituation can be partially restored by costimulation with 100 microm UTP.
      Background application of UTP increases habituation to both ATP and 2MeSATP. This
      suggests that ATP-sensitive metabotropic (P2Y) receptors play a role in the
      habituation process. Finally, although Ca2+ influx through voltage-operated
      calcium channels does not appear to contribute to secretion during ATP
      stimulation, blocking these channels with nicardipine increases habituation. This
      suggests a role for voltage-operated calcium channels in the habituation process.

PMID- 15479233
TI  - Differential effects of RU486 reveal distinct mechanisms for glucocorticoid
      repression of prostaglandin E release.
AB  - In A549 pulmonary cells, the dexamethasone- and budesonide-dependent repression
      of interleukin-1beta-induced prostaglandin E2 release was mimicked by the steroid
      antagonist, RU486. Conversely, whereas dexamethasone and budesonide were highly
      effective inhibitors of interleukin-1beta-induced cyclooxygenase
      (COX)/prostaglandin E synthase (PGES) activity and COX-2 expression, RU486 (<1
      microm) was a poor inhibitor, but was able to efficiently antagonize the effects
      of dexamethasone and budesonide. In addition, both dexamethasone and RU486
      repressed [3H]arachidonate release, which is consistent with an effect at the
      level of phospholipase A2 activity. By contrast, glucocorticoid response element
      dependent transcription was unaffected by RU486 but induced by dexamethasone and
      budesonide, whilst dexamethasone- and budesonide-dependent repression of nuclear
      factor-kappaB-dependent transcription was maximally 30-40% and RU486 (<1 microm)
      was without significant effect. Thus, two pharmacologically distinct mechanisms
      of glucocorticoid-dependent repression of prostaglandin E2 release are revealed.
      First, glucocorticoid-dependent repression of arachidonic acid is mimicked by
      RU486 and, second, repression of COX/PGES is antagonized by RU486. Finally,
      whilst all compounds induced glucocorticoid receptor translocation, no role for
      glucocorticoid response element-dependent transcription is supported in these
      inhibitory processes and only a limited role for glucocorticoid-dependent
      inhibition of nuclear factor-kappaB in the repression of COX-2 is indicated.

PMID- 15479234
TI  - The Y42H mutation in medium-chain acyl-CoA dehydrogenase, which is prevalent in
      babies identified by MS/MS-based newborn screening, is temperature sensitive.
AB  - Medium-chain acyl-CoA dehydrogenase (MCAD) is a homotetrameric flavoprotein which
      catalyses the initial step of the beta-oxidation of medium-chain fatty acids.
      Mutations in MCAD may cause disease in humans. A Y42H mutation is frequently
      found in babies identified by newborn screening with MS/MS, yet there are no
      reports of patients presenting clinically with this mutation. As a basis for
      judging its potential consequences we have examined the protein phenotype of the
      Y42H mutation and the common disease-associated K304E mutation. Our studies of
      the intracellular biogenesis of the variant proteins at different temperatures in
      isolated mitochondria after in vitro translation, together with studies of
      cultured patient cells, indicated that steady-state levels of the Y42H variant in
      comparison to wild-type were decreased at higher temperature though to a lesser
      extent than for the K304E variant. To distinguish between effects of temperature
      on folding/assembly and the stability of the native enzyme, the thermal stability
      of the variant proteins was studied after expression and purification by dye
      affinity chromatography. This showed that, compared with the wild-type enzyme,
      the thermostability of the Y42H variant was decreased, but not to the same degree
      as that of the K304E variant. Substrate binding, interaction with the natural
      electron acceptor, and the binding of the prosthetic group, FAD, were only
      slightly affected by the Y42H mutation. Our study suggests that Y42H is a
      temperature sensitive mutation, which is mild at low temperatures, but may have
      deleterious effects at increased temperatures.

PMID- 15479235
TI  - A steady-state modeling approach to validate an in vivo mechanism of the GAL
      regulatory network in Saccharomyces cerevisiae.
AB  - Cellular regulation is a result of complex interactions arising from DNA-protein
      and protein-protein binding, autoregulation, and compartmentalization and
      shuttling of regulatory proteins. Experiments in molecular biology have
      identified these mechanisms recruited by a regulatory network. Mathematical
      models may be used to complement the knowledge-base provided by in vitro
      experimental methods. Interactions identified by in vitro experiments can lead to
      the hypothesis of multiple candidate models explaining the in vivo mechanism. The
      equilibrium dissociation constants for the various interactions and the total
      component concentration constitute constraints on the candidate models. In this
      work, we identify the most plausible in vivo network by comparing the output
      response to the experimental data. We demonstrate the methodology using the GAL
      system of Saccharomyces cerevisiae for which the steady-state analysis reveals
      that Gal3p neither dimerizes nor shuttles between the cytoplasm and the nucleus.

PMID- 15479236
TI  - Cloning, expression and interaction of human T-cell receptors with the bacterial
      superantigen SSA.
AB  - Superantigens (SAgs) are a class of disease-causing and immunostimulatory
      proteins of bacterial or viral origin that activate a large number of T-cells
      through interaction with the Vbeta domain of T-cell receptors (TCRs). In this
      study, recombinant TCR beta chains were constructed with human variable domains
      Vbeta5.2, Vbeta1 and Vbeta2.1, expressed as inclusion bodies, refolded and
      purified. The Streptococcus pyogenes SAg SSA-1 was cloned and expressed as a
      soluble periplasmic protein. SSA-1 was obtained both as a monomer and a dimer
      that has an intermolecular disulfide bond. We analyzed the biological activity of
      the recombinant SAgs by proliferation assays. The results suggest that SSA
      dimerization occludes the TCR interaction site. Naturally occurring SSA
      dimerization was also observed in supernatants of S. pyogenes isolates. An SSA
      mutant [SSA(C26S)] was produced to eliminate the Cys responsible for
      dimerization. Affinity assays using a resonant biosensor showed that both the
      mutant and monomeric wild type SSA have affinity for human Vbeta5.2 and Vbeta1
      with Kd of 9-11 microm with a fast kass and a moderately fast kdiss. In spite of
      the reported stimulation of Vbeta2.1 bearing T-cells by SSA, we observed no
      measurable interaction.

PMID- 15479237
TI  - Optimization of an Escherichia coli system for cell-free synthesis of selectively
      N-labelled proteins for rapid analysis by NMR spectroscopy.
AB  - Cell-free protein synthesis offers rapid access to proteins that are selectively
      labelled with [15N]amino acids and suitable for analysis by NMR spectroscopy
      without chromatographic purification. A system based on an Escherichia coli cell
      extract was optimized with regard to protein yield and minimal usage of 15N
      labelled amino acid, and examined for the presence of metabolic by-products which
      could interfere with the NMR analysis. Yields of up to 1.8 mg of human
      cyclophilin A per mL of reaction medium were obtained by expression of a
      synthetic gene. Equivalent yields were obtained using transcription directed by
      either T7 or tandem phage lambdapR and pL promoters, when the reactions were
      supplemented with purified phage T7 or E. coli RNA polymerase. Nineteen samples,
      each selectively labelled with a different 15N-enriched amino acid, were produced
      and analysed directly by NMR spectroscopy after ultracentrifugation. Cross-peaks
      from metabolic by-products were evident in the 15N-HSQC spectra of 13 of the
      samples. All metabolites were found to be small molecules that could be separated
      readily from the labelled proteins by dialysis. No significant transamination
      activity was observed except for [15N]Asp, where an enzyme in the cell extract
      efficiently converted Asp-->Asn. This activity was suppressed by replacing the
      normally high levels of potassium glutamate in the reaction mixture with ammonium
      or potassium acetate. In addition, the activity of peptide deformylase appeared
      to be generally reduced in the cell-free expression system.

PMID- 15479238
TI  - Three novel carp CXC chemokines are expressed early in ontogeny and at nonimmune
      sites.
AB  - Three novel CXC chemokines were identified in common carp (Cyprinus carpio L.)
      through homology cloning. Phylogenetic analyses show that one of the three CXC
      chemokines is an unambiguous orthologue of CXCL14, whereas both others are
      orthologues of CXCL12, and were named CXCL12a and CXCL12b. Percentages of amino
      acid identity between each of these carp chemokines and their human and mouse
      orthologues are markedly higher than those reported previously for other carp CXC
      chemokines, suggestive of involvement in vital processes, which have allowed for
      relatively few structural changes. Furthermore, all three novel carp CXC
      chemokines are expressed during early development, in contrast to established
      immune CXC chemokines. In noninfected adult carp, CXCL12b and CXCL14 are
      predominantly expressed in the brain. CXCL12a is highly expressed in kidney and
      anterior kidney, but its expression is still more abundant in brain than any
      other carp CXC chemokine. Clearly, these chemokines must play key roles in the
      patterning and maintenance of the (developing) vertebrate central nervous system.

PMID- 15479239
TI  - X-ray structure of peptidyl-prolyl cis-trans isomerase A from Mycobacterium
      tuberculosis.
AB  - Peptidyl-prolyl cis-trans isomerases (EC 5.2.1.8) catalyse the interconversion of
      cis and trans peptide bonds and are therefore considered to be important for
      protein folding. They are also thought to participate in processes such as
      signalling, cell surface recognition, chaperoning and heat-shock response. Here
      we report the soluble expression of recombinant Mycobacterium tuberculosis
      peptidyl-prolyl cis-trans isomerase PpiA in Escherichia coli, together with an
      investigation of its structure and biochemical properties. The protein was shown
      to be active in a spectrophotometric assay, with an estimated kcat/Km of 2.0 x
      10(6) m(-1).s(-1). The X-ray structure of PpiA was solved by molecular
      replacement, and refined to a resolution of 2.6 A with R and Rfree values of
      21.3% and 22.9%, respectively. Comparisons to known structures show that the PpiA
      represents a slight variation on the peptidyl-prolyl cis-trans isomerase fold,
      previously not represented in the Protein Data Bank. Inspection of the active
      site suggests that specificity for substrates and cyclosporin A will be similar
      to that found for most other enzymes of this structural family. Comparison to the
      sequence of the second M. tuberculosis enzyme, PpiB, suggests that binding of
      peptide substrates as well as cyclosporin A may differ in that case.

PMID- 15479240
TI  - Crystal structures of the human SUMO-2 protein at 1.6 A and 1.2 A resolution:
      implication on the functional differences of SUMO proteins.
AB  - The SUMO proteins are a class of small ubiquitin-like modifiers. SUMO is attached
      to a specific lysine side chain on the target protein via an isopeptide bond with
      its C-terminal glycine. There are at least four SUMO proteins in humans, which
      are involved in protein trafficking and targeting. A truncated human SUMO-2
      protein that contains residues 9-93 was expressed in Escherichia coli and
      crystallized in two different unit cells, with dimensions of a=b=75.25 A, c=29.17
      A and a=b=74.96 A, c=33.23 A, both belonging to the rhombohedral space group R3.
      They diffracted X-rays to 1.6 A and 1.2 A resolution, respectively. The
      structures were determined by molecular replacement using the yeast SMT3 protein
      as a search model. Subsequent refinements yielded R/Rfree values of 0.169/0.190
      and 0.119/0.185, at 1.6 A and 1.2 A, respectively. The peptide folding of SUMO-2
      consists of a half-open beta-barrel and two flanking alpha-helices with secondary
      structural elements arranged as betabetaalphabetabetaalphabeta in the sequence,
      identical to those of ubiquitin, SMT3 and SUMO-1. Comparison of SUMO-2 with SUMO
      1 showed a surface region near the C terminus with significantly different charge
      distributions. This may explain their distinct intracellular locations. In
      addition, crystal-packing analysis suggests a possible trimeric assembly of the
      SUMO-2 protein, of which the biological significance remains to be determined.

PMID- 15479241
TI  - Chloroplast phosphoglycerate kinase from Euglena gracilis: endosymbiotic gene
      replacement going against the tide.
AB  - Two chloroplast phosphoglycerate kinase isoforms from the photosynthetic
      flagellate Euglena gracilis were purified to homogeneity, partially sequenced,
      and subsequently cDNAs encoding phosphoglycerate kinase isoenzymes from both the
      chloroplast and cytosol of E. gracilis were cloned and sequenced. Chloroplast
      phosphoglycerate kinase, a monomeric enzyme, was encoded as a polyprotein
      precursor of at least four mature subunits that were separated by conserved
      tetrapeptides. In a Neighbor-Net analysis of sequence similarity with homologues
      from numerous prokaryotes and eukaryotes, cytosolic phosphoglycerate kinase of E.
      gracilis showed the highest similarity to cytosolic and glycosomal homologues
      from the Kinetoplastida. The chloroplast isoenzyme of E. gracilis did not show a
      close relationship to sequences from other photosynthetic organisms but was most
      closely related to cytosolic homologues from animals and fungi.

PMID- 15479242
TI  - Effects of cardiomyopathic mutations on the biochemical and biophysical
      properties of the human alpha-tropomyosin.
AB  - Mutations in the protein alpha-tropomyosin (Tm) can cause a disease known as
      familial hypertrophic cardiomyopathy. In order to understand how such mutations
      lead to protein dysfunction, three point mutations were introduced into cDNA
      encoding the human skeletal tropomyosin, and the recombinant Tms were produced at
      high levels in the yeast Pichia pastoris. Two mutations (A63V and K70T) were
      located in the N-terminal region of Tm and one (E180G) was located close to the
      calcium-dependent troponin T binding domain. The functional and structural
      properties of the mutant Tms were compared to those of the wild type protein.
      None of the mutations altered the head-to-tail polymerization, although slightly
      higher actin binding was observed in the mutant Tm K70T, as demonstrated in a
      cosedimentation assay. The mutations also did not change the cooperativity of the
      thin filament activation by increasing the concentrations of Ca2+. However, in
      the absence of troponin, all mutant Tms were less effective than the wild type in
      regulating the actomyosin subfragment 1 Mg2+ ATPase activity. Circular dichroism
      spectroscopy revealed no differences in the secondary structure of the Tms.
      However, the thermally induced unfolding, as monitored by circular dichroism or
      differential scanning calorimetry, demonstrated that the mutants were less stable
      than the wild type. These results indicate that the main effect of the mutations
      is related to the overall stability of Tm as a whole, and that the mutations have
      only minor effects on the cooperative interactions among proteins that constitute
      the thin filament.

PMID- 15479243
TI  - 17beta-hydroxysteroid dehydrogenase type 11 is a major peroxisome proliferator
      activated receptor alpha-regulated gene in mouse intestine.
AB  - In order to study the role of peroxisome proliferator-activated receptor alpha in
      mouse intestine, its agonist-induced proteins were identified by peptide mass
      fingerprinting followed by Northern blot analysis using their cDNAs. One of the
      most remarkably induced proteins was identified as 17beta-hydroxysterol
      dehydrogenase type 11. Its very rapid induction by various agonists was most
      efficient in intestine and then in liver. These findings together with recently
      reported results showing the enzyme family's wide substrate spectrum, including
      not only glucocorticoids and sex steroids but also bile acids, fatty acids and
      branched chain amino acids, suggest new roles for both peroxisome proliferator
      activated receptor alpha and 17beta-hydroxysterol dehydrogenase type 11 in lipid
      metabolism and/or detoxification in the intestine.

PMID- 15479244
TI  - Probing the unfolding region of ribonuclease A by site-directed mutagenesis.
AB  - Ribonuclease A contains two exposed loop regions, around Ala20 and Asn34. Only
      the loop around Ala20 is sufficiently flexible even under native conditions to
      allow cleavage by nonspecific proteases. In contrast, the loop around Asn34
      (together with the adjacent beta-sheet around Thr45) is the first region of the
      ribonuclease A molecule that becomes susceptible to thermolysin and trypsin under
      unfolding conditions. This second region therefore has been suggested to be
      involved in early steps of unfolding and was designated as the unfolding region
      of the ribonuclease A molecule. Consequently, modifications in this region should
      have a great impact on the unfolding and, thus, on the thermodynamic stability.
      Also, if the Ala20 loop contributes to the stability of the ribonuclease A
      molecule, rigidification of this flexible region should stabilize the entire
      protein molecule. We substituted several residues in both regions without any
      dramatic effects on the native conformation and catalytic activity. As a result
      of their remarkably differing stability, the variants fell into two groups
      carrying the mutations: (a) A20P, S21P, A20P/S21P, S21L, or N34D; (b) L35S, L35A,
      F46Y, K31A/R33S, L35S/F46Y, L35A/F46Y, or K31A/R33S/F46Y. The first group showed
      a thermodynamic and kinetic stability similar to wild-type ribonuclease A,
      whereas both stabilities of the variants in the second group were greatly
      decreased, suggesting that the decrease in DeltaG can be mainly attributed to an
      increased unfolding rate. Although rigidification of the Ala20 loop by
      introduction of proline did not result in stabilization, disturbance of the
      network of hydrogen bonds and hydrophobic interactions that interlock the
      proposed unfolding region dramatically destabilized the ribonuclease A molecule.

PMID- 15479245
TI  - Bacterial endosymbionts of insects: insights from comparative genomics.
AB  - The development of molecular techniques for the study of uncultured bacteria
      allowed the extensive study of the widespread association between insects and
      intracellular symbiotic bacteria. Most of the bacterial endosymbionts involved in
      such associations are gamma-proteobacteria, closely related to Escherichia coli.
      In recent years, five genomes from insect endosymbionts have been sequenced,
      allowing the performance of extensive genome comparative analysis that, as a
      complement of phylogenetic studies, and analysis on individual genes, can help to
      understand the different traits of this particular association, including how the
      symbiotic process is established, the explanation of the special features of
      these microbial genomes, the bases of this intimate association and the possible
      future that awaits the endosymbionts with extremely reduced genomes.

PMID- 15479246
TI  - Streptomycin as a selective agent to facilitate recovery and isolation of
      introduced and indigenous Sphingomonas from environmental samples.
AB  - Sphingomonas is an organism of major interest for the degradation of organic
      contaminants in soils and other environments. A medium based on the
      aminoglycoside antibiotic streptomycin (Sm) was developed, which, together with
      the yellow pigmentation of Sphingomonas, facilitated the detection, recovery and
      quantification of culturable Sphingomonas from soils. All 29 previously described
      bacterial strains belonging to 17 different Sphingomonas species were able to
      grow on mineral media containing 200 microg ml(-1) streptomycin, showing that the
      capacity to resist high concentrations of Sm is a common characteristic within
      Sphingomonas. Incorporation of Sm into the mineral medium led to a significant
      reduction in the background microbial population and a concomitant 100 times more
      sensitive detection of Sphingomonas inoculated in non-sterile soil matrices. The
      Sm-containing medium was used to examine a variety of hydrocarbon-contaminated
      soils for the presence and biodiversity of Sphingomonas. Incorporation of Sm in
      the medium led to a significant increase in the number of yellow-pigmented
      colonies. Comparison of contaminated and non-contaminated soils derived from the
      same site revealed colonization by culturable yellow-pigmented Sm-resistant
      bacteria of the polluted location solely. Both yellow and non-yellow-pigmented
      colonies were purified from plates containing glucose and Sm, and BOX-polymerase
      chain reaction (PCR) was used to sort out clonally related strains.
      Representative strains from the major BOX-PCR clusters were identified using FAME
      and partial 16S rRNA gene sequencing. Forty-eight of 58 Sm-resistant isolates
      were identified as Sphingomonas sp. Streptomycin-resistant Sphingomonas isolates
      generated BOX-PCR diversity patterns that were site dependent and represented
      different species mainly belonging to Sphingomonas subgroups containing species
      formerly designated as Sphingopyxis and Sphingobium. The ability to degrade
      phenanthrene was only found in a minority of the Sphingomonas isolates, which all
      originated from soils containing high phenanthrene concentrations.

PMID- 15479247
TI  - Widespread association of a Rickettsiales-like bacterium with reef-building
      corals.
AB  - White band disease type I (WBD I) has been a major cause of the dramatic decline
      of Acroporid coral populations throughout the Caribbean during the last two
      decades, yet the aetiological agent of this disease is unknown. In this study,
      the bacterial communities associated with both healthy and diseased Acropora
      species were compared by 16S rDNA analyses. The bacterial communities of both
      healthy and diseased Acropora spp. were dominated by a single ribotype with 90%
      identity to a bacterium in the order Rickettsiales. Screening by nested PCR
      specific to the coral-associated Rickettsiales 1 (CAR1) bacterium showed that
      this microbe was widespread in both healthy and diseased A. cervicornis and A.
      palmata corals from 'healthy' (i.e. low WBD I incidence) and 'stressed' reefs
      (i.e. high WBD I incidence). These results indicate that there were no dramatic
      changes in the composition of the microbial community associated with WBD I. CAR1
      was also associated with non-Acroporid corals of the Caribbean, as well as with
      two Acroporid corals native to the Pacific. CAR1 was not present in the water
      column. This bacterium was also absent from preserved Caribbean Acroporid samples
      collected between 1937 and 1980 before the outbreak of WBD I. These results
      suggest CAR1 is a relatively new bacterial associate of Acroporids and that a non
      bacterial pathogen might be the cause of WBD I.

PMID- 15479248
TI  - Investigations on epiphytic living Pseudomonas species from Malus domestica with
      an antagonistic effect to Venturia inaequalis on isolated plant cuticle
      membranes.
AB  - In order to understand better the survival and mutual interaction of epiphytic
      bacteria and fungi on apple plants, bacteria collected from these plants were
      cultivated on intact adaxial, stoma free cuticle membranes originally obtained
      from apple. The bacteria were labelled with luciferase genes from Vibrio harveyi
      in order to follow up their development and activity on the isolated cuticles.
      Our finding was that the epiphytic bacteria can have access to nutrients below
      the cuticle without causing damage to these cuticular membranes. Bacterial
      proteins may enable this nutrient mobilization and we found, indeed, that more
      than 46 proteins that must have been delivered by the bacteria in response to
      interaction with the cuticles as they could be found below the cuticle membrane.
      Eight major representatives of this group of external proteins have been
      sequenced with electron spray quadrupole time of flight mass spectrometry and
      subsequently identified by data base homology search as a flagellin, a porin type
      protein and proteins that are involved in amino acid recruitment and metabolism.

PMID- 15479249
TI  - Acetoclastic and hydrogenotrophic methane production and methanogenic populations
      in an acidic West-Siberian peat bog.
AB  - Sites in the West Siberian peat bog 'Bakchar' were acidic (pH 4.2-4.8), low in
      nutrients, and emitted CH4 at rates of 0.2-1.5 mmol m(-2) h(-1). The vertical
      profile of delta13CH4 and delta13CO2 dissolved in the porewater indicated
      increasing isotope fractionation and thus increasing contribution of H2/CO2
      dependent methanogenesis with depth. The anaerobic microbial community at 30-50
      cm below the water table produced CH4 with optimum activity at 20-25 degrees C
      and pH 5.0-5.5 respectively. Inhibition of methanogenesis with 2-bromo-ethane
      sulphonate showed that acetate, phenyl acetate, phenyl propionate and caproate
      were important intermediates in the degradation pathway of organic matter to CH4.
      Further degradation of these intermediates indicated that 62-72% of the CH4 was
      ultimately derived from acetate, the remainder from H2/CO2. Turnover times of [2
      14C]acetate were on the order of 2 days (15, 25 degrees C) and accounted for 60
      65% of total CH4 production. Conversion of 14CO2 to 14CH4 accounted for 35-43% of
      total CH4 production. These results showed that acetoclastic and hydrogenotrophic
      methanogenesis operated closely at a ratio of approximately 2 : 1 irrespective of
      the incubation temperature (4, 15 and 25 degrees C). The composition of the
      archaeal community was determined in the peat samples by terminal restriction
      fragment length polymorphism (T-RFLP) analysis and sequencing of amplified SSU
      rRNA gene fragments, and showed that members of Methanomicrobiaceae,
      Methanosarcinaceae and Rice cluster II (RC-II) were present. Other, presumably
      non-methanogenic archaeal clusters (group III, RC-IV, RC-V, RC-VI) were also
      detected. Fluorescent in situ hybridization (FISH) showed that the number of
      Bacteria decreased (from 24 x 10(7) to 4 x 10(7) cells per gram peat) with depth
      (from 5 to 55 cm below the water table), whereas the numbers of Archaea slightly
      increased (from 1 x 10(7) to 2 x 10(7) cells per gram peat). Methanosarcina spp.
      accounted for about half of the archaeal cells. Our results show that both
      hydrogenotrophic and acetoclastic methanogenesis are an integral part of the CH4
      producing pathway in acidic peat and were represented by appropriate methanogenic
      populations.

PMID- 15479250
TI  - Changes in population structure of the soilborne fungus Gaeumannomyces graminis
      var. tritici during continuous wheat cropping.
AB  - A method was developed to assess the genetic structure of Gaeumannomyces graminis
      var. tritici (Ggt) populations and test the hypothesis of an association between
      disease level in the field with changes in pathogen populations. A long-term
      wheat monoculture experiment, established since 1994, generated different take
      all epidemics with varying the number of wheat crop successions in the 1999-2000
      cropping season. Genetic polymorphism in Ggt populations was investigated over
      natural, local epidemics. Four populations of 30 isolates were isolated from
      necrotic wheat roots in a first, third, fourth, and sixth wheat crop in the same
      year. Each Ggt isolate was characterized with RAPD (Random Amplification
      Polymorphism DNA) markers and AFLP (Amplified Fragment Length Polymorphism)
      fingerprinting. Seventeen multilocus genotypes based on the combination of RAPD
      and AFLP markers were identified among all these populations. The 120 isolates
      were divided into two main groups, G1 and G2, according to bootstrap values
      higher than 86%, except for an unique isolate from the third wheat crop. Within
      each group, populations ranged between 93 and 100% similarity. Both groups
      included isolates collected from the first, third, fourth or sixth wheat crop.
      However, G1 group profiles dominated amongst isolates sampled in the first and
      the sixth wheat crops, whereas G2 group profiles largely dominated amongst
      isolates collected from the third and fourth wheat crops. Aggressiveness of group
      G2 (38%) was significantly greater than that of G1 (29.5%). These results suggest
      that changes in Ggt population structure occur during continuous wheat cropping.
      The distinction of two Ggt groups provides a simple basis for further spatio
      temporal analysis of Ggt population during polyetic take-all decline.

PMID- 15479251
TI  - Design of new promoters and of a dual-bioreporter based on cross-activation by
      the two regulatory proteins XylR and HbpR.
AB  - The HbpR protein is the sigma54-dependent transcription activator for 2
      hydroxybiphenyl degradation in Pseudomonas azelaica. The ability of HbpR and
      XylR, which share 35% amino acid sequence identity, to cross-activate the PhbpC
      and Pu promoters was investigated by determining HbpR- or XylR-mediated
      luciferase expression and by DNA binding assays. XylR measurably activated the
      PhbpC promoter in the presence of the effector m-xylene, both in Escherichia coli
      and Pseudomonas putida. HbpR weakly stimulated the Pu promoter in E. coli but not
      in P. azelaica. Poor HbpR-dependent activation from Pu was caused by a weak
      binding to the operator region. To create promoters efficiently activated by both
      regulators, the HbpR binding sites on PhbpC were gradually changed into the XylR
      binding sites of Pu by site-directed mutagenesis. Inducible luciferase expression
      from mutated promoters was tested in E. coli on a two plasmid system, and from
      mono copy gene fusions in P. azelaica and P. putida. Some mutants were
      efficiently activated by both HbpR and XylR, showing that promoters can be
      created which are permissive for both regulators. Others achieved a higher XylR
      dependent transcription than from Pu itself. Mutants were also obtained which
      displayed a tenfold lower uninduced expression level by HbpR than the wild-type
      PhbpC, while keeping the same maximal induction level. On the basis of these
      results, a dual-responsive bioreporter strain of P. azelaica was created,
      containing both XylR and HbpR, and activating luciferase expression from the same
      single promoter independently with m-xylene and 2-hydroxybiphenyl.

PMID- 15479252
TI  - Evaluating single-base-pair discriminating capability of planar oligonucleotide
      microchips using a non-equilibrium dissociation approach.
AB  - The capability of planar rRNA-based oligonucleotide microarrays for single-base
      pair discrimination was evaluated using an approach that compares the non
      equilibrium dissociation profiles and dissociation temperatures (Tds) of all
      probe-target duplexes simultaneously. Three sets of 16S rRNA gene specific probes
      at different levels of specificity were used along with their counter probes for
      individual sets having either one or two mismatches (MM) to their targets at
      specific external (next to terminus) and various internal positions. Criteria
      based on the Td approach and a discrimination index (DI) were proven to be
      competent in discriminating PM from internal MM duplexes, but not always for
      external MM duplexes. Maximal DI for separating PM duplexes from ones with two
      and one internal MM usually occurred at temperatures approximately 5-10 degrees C
      and 10-15 degrees C, respectively, higher than the Tds of the PM duplexes.
      Washing buffer type and salt concentration, and MM number and position were shown
      statistically to affect dissociation profiles, Td, and single-base-pair
      discriminating capability. The reusability potential of the planar microchip was
      further demonstrated.

PMID- 15479255
TI  - Internal apical resorption and its correlation with the type of apical lesion.
AB  - AIM: To determine the presence of various periapical pathologies and their
      association with the presence and extent of internal apical inflammatory root
      resorption in human teeth. METHODOLOGY: A total of 75 root apices from extracted
      teeth with periapical lesions were examined. Semi-serial sections of soft tissue
      lesions were stained with HE. The lesions were classified as non-cystic or
      cystic, and according to the degree of abscess severity: 0, 1, 2 or 3. The apices
      were reduced to 3 mm in length and longitudinally cut so that the internal aspect
      could be analyzed under scanning electron microscopy (SEM). Internal root
      resorption was also classified as 0, 1, 2 or 3 according to the extent of the
      resorbed area. Additionally, six vital teeth were used as a control. RESULTS: Non
      cystic lesions with severe abscesses were the most common finding (70.7%), while
      20% of the lesions were cystic (4% little or no abscess; 16% severe abscesses).
      Non-cystic lesions with little or no abscess comprised 9.3% of the sample. Of the
      root canals containing periapical lesions, 48% had internal apical resorption in
      more than half of the area, while 25.3% of the sample had no internal resorption.
      Resorption degree 1 was identified in 12% of the cases, and 14.7% showed
      resorption degree 2. The control group displayed significantly less internal
      resorption than the test groups. CONCLUSIONS: Most periapical lesions (86.7%),
      whether cystic (16.0%) or non-cystic (70.7%), showed large collections of acute
      inflammatory cells. Apical internal resorption was present in 74.7% of roots and
      was associated with periapical lesions. There was no correlation between internal
      apical resorption and the histological diagnosis of the lesions.

PMID- 15479256
TI  - A comparative histological evaluation of the biocompatibility of materials used
      in apical surgery.
AB  - AIM: To evaluate the biological properties of a variety of materials that could
      be used in apical surgery. METHODOLOGY: The intraosseous implant technique
      recommended by the FDI (1980) and ADA (1982) was used to test the following
      materials: zinc oxide-eugenol (ZOE), mineral trioxide aggregate (MTA), and Z-100
      light-cured composite resin. Thirty guinea-pigs, 10 for each material, divided
      into experimental periods of 4 and 12 weeks, received one implant on each side of
      the lower jaw symphysis. The connective tissue response alongside the lateral
      wall outside the cup served as a negative control for the technique. At the end
      of the observation periods, the animals were killed and the specimens prepared
      for routine histological examination to evaluate their biocompatibility. RESULTS:
      The reaction of the tissue to the materials diminished with time. The ZOE cement
      was highly toxic during the 4-week experimental period, but this profile changed
      significantly after 12 weeks, when it showed biocompatible characteristics. MTA
      and Z-100 showed biocompatibility in this test model at both time periods.
      CONCLUSIONS: MTA and Z-100 composite were biocompatible at 4 and 12 weeks in this
      experimental model.

PMID- 15479257
TI  - In vitro immunoexpression of extracellular matrix proteins in dental pulpal and
      gingival human fibroblasts.
AB  - AIM: To compare the expression of extracellular matrix (ECM) components in human
      pulpal and gingival fibroblasts in vitro. METHODOLOGY: Cultured dental pulp
      fibroblasts and gingival mucosa fibroblasts were used. Tenascin (TN), fibronectin
      (FN), type I (col I) and III collagen (col III) and osteonectin (ONEC) were
      detected by immunofluorescence. Main morphological characteristics were also
      analysed by light microscopy (LM) and transmission electron microscopy. RESULTS:
      The results revealed different expression patterns of the proteins. TN and ONEC
      were only immunoexpressed by pulpal fibroblast cells, suggesting a role of these
      glycoproteins in formation of mineralized tissues. FN and col I were present in
      the cytoplasms of both cell types. No expression of col III was detected.
      Different morphological characteristics were visualized under LM, in which pulpal
      fibroblasts were spindle-shaped with a wide cytoplasm, while gingival fibroblast
      cells exhibited stellate/pyramidal configuration, with rounded nuclei. However,
      ultrastructurally, both cell lineages showed very well developed rough
      endoplasmatic reticulum and Golgi complex. CONCLUSIONS: Due to the
      immunodetection of TN and ONEC on pulpal fibroblasts, the present findings
      demonstrated that a pulpal fibroblast cell is similar to an osteoblastic cell
      rather than an undifferentiated mesenchymal cell, such as a gingival fibroblast
      cell. Functional differences between the two cell lines may then be suggested.

PMID- 15479258
TI  - Antimicrobial susceptibility of Enterococcus faecalis isolated from canals of
      root filled teeth with periapical lesions.
AB  - AIM: To test, in vitro, the susceptibility to different antibiotics of
      Enterococcus faecalis isolates from canals of root filled teeth with periapical
      lesions. METHODOLOGY: Twenty-one E. faecalis isolates, from canals of root filled
      teeth with persisting periapical lesions, were tested for their antibiotic
      susceptibilities. The following antibiotics were used: benzylpenicillin,
      amoxicillin, amoxicillin-clavulanic acid, erythromycin, azithromycin, vancomycin,
      chloramphenicol, tetracycline, doxycycline, ciprofloxacin and moxifloxacin.
      Minimal inhibitory concentrations (MICs) for the antimicrobial agents were
      determined using the E-test System (AB BIODISK, Solna, Sweden), and the E.
      faecalis strains classified as susceptible or resistant according to the
      guidelines of National Committee for Clinical Laboratory Standards (NCCLS). The
      strains were also tested for beta-lactamase production with nitrocefin (Oxoid,
      Basingstoke, UK). RESULTS: All strains were susceptible to penicillins in vitro,
      however, the MICs of amoxicillin and amoxicillin-clavulanic acid (MIC(90) = 0.75
      microg mL(-1)) were lower than for benzylpenicillin (MIC(90) = 3.0 microg mL(
      1)). All strains studied were also susceptible to vancomycin and moxifloxacin,
      whilst 95.2% were susceptible to chloramphenicol. Amongst the isolates, 85.7%
      were susceptible to tetracycline and doxycycline and 80.9% to ciprofloxacin. The
      MIC of erythromycin ranged from 0.38 to >256 microg mL(-1); only 28.5% of the
      strains were susceptible (MIC < or = 0.5 microg mL(-1)). Limited susceptibility
      was also observed with azithromycin which was active against only 14.2% of
      isolates. No strains produced beta-lactamase. CONCLUSION: Enterococcus faecalis
      isolates were completely susceptible, in vitro, to amoxicillin, amoxicillin
      clavulanic acid, vancomycin and moxifloxacin. Most isolates were susceptible to
      chloramphenicol, tetracycline, doxycycline or ciprofloxacin. Erythromycin and
      azithromycin were least effective.

PMID- 15479259
TI  - Survival of surgical endodontic treatment performed in a dental teaching
      hospital: a cohort study.
AB  - AIM: To assess the survival function of surgical endodontic treatment performed
      at least 1 year before in a dental teaching hospital. METHODOLOGY: A total of 194
      teeth surgically treated between 1991 and 2001 were recalled and examined
      clinically and radiographically using a set of strict criteria. The Kaplan-Meier
      method and log rank test were used to evaluate the survival time. Confounding
      factors were examined by Cox regression analysis. RESULTS: The median survival
      time of the 154 first-time surgically treated teeth was 92.1 months (95% CI: 40.9
      143.4) and that of the 40 resurgery cases was 39.1 months (95% CI: 6.1-72.1) up
      to the date of recall. There was a significant difference in the length of
      survival between the two groups. For those first-time surgery cases, the
      preoperative marginal bone loss and the operator had a significant influence on
      the survival time (P < 0.05). CONCLUSIONS: The survival of surgical endodontic
      treatment declined nonlinearly with time. The preoperative marginal bone loss,
      operator and resurgery were important factors affecting the survival of this
      treatment modality.

PMID- 15479260
TI  - A scanning electron microscope study of plaque accumulation on silk and PVDF
      suture materials in oral mucosa.
AB  - AIM: To examine plaque accumulation on silk and polyvinylidene fluoride (PVDF)
      sutures at different time intervals. METHODOLOGY: Twenty-one male albino rabbits
      received sutures under general and local anaesthesia. After 3, 5 and 7 days
      sutures were removed and processed for scanning electron microscope (SEM)
      observation. The Friedman and the Wilcoxon tests were used to compare
      contamination on PVDF and silk suture materials at different time intervals.
      RESULTS: At all time intervals, the whole surface of silk sutures was covered
      with a thick layer of bacterial plaque and debris. Microorganisms and blood cells
      on the surface and between the filaments of the silk suture material were
      observed. Light debris appeared around the knot area of PVDF sutures after 3
      days. At 5 and 7 days, contamination could be seen in scattered areas along the
      suture material. The average contaminated area was smaller on PVDF suture
      materials, which were removed at 5 than at 7 days after insertion. At 3 days,
      PVDF sutures showed significantly less contamination than at 5 and 7 days (P =
      0.002). There were statistically significant differences between silk and PVDF
      sutures at 3, 5 and 7 days. CONCLUSION: SEM observation showed that PVDF sutures
      were contaminated less than silk sutures at 3, 5 and 7 days.

PMID- 15479261
TI  - The annual frequency of root fillings, tooth extractions and pulp-related
      procedures in Danish adults during 1977-2003.
AB  - AIM: To investigate a hypothesized long-time decrease of endodontic treatment in
      a population with low caries prevalence. METHODOLOGY: A Danish nationwide
      database including almost all dental diagnostic, prophylactic and therapeutic
      procedures performed in Danish adults was available. Data on the annual
      frequencies of root fillings, extractions, pulpotomies, direct pulp cappings and
      stepwise excavations between 1977 and 2003 were analysed. Data on pulpal and
      periapical diagnoses were not available and on patients age and gender only from
      1996. RESULTS: Between 1977 and 2003 the annual number of root filled canals
      increased from 268,223 to 364,867 (36%). The annual number of root filled teeth
      increased from 160,119 to 191,803 (20%). During the period, the annually
      registered patients increased by 16%. Calculated per 1000 patients, the number of
      root fillings showed a statistically significant increase of 17%. In root filled
      teeth the canal/tooth ratio increased from 1.67 to 1.96. Root fillings were
      frequently recorded in all age groups with the bulk of treatments performed on
      patients between 40 and 60 years of age. At a total population level, the rate of
      root fillings decreased among younger individuals and increased among older. The
      annual number of tooth extractions was more than halved from 656,624 in 1977 to
      346,490 in 2003. Pulpotomies decreased markedly over the period and less than 10
      treatments per 1000 patients were noted for pulp capping as well as stepwise
      excavation procedures. CONCLUSIONS: The present study failed to show a long-time
      decrease of endodontic treatment in a population with low caries prevalence. On
      the contrary, an increase of root filled canals was observed between 1977 and
      2003, which was probably due to a reduction of the tooth extraction rate and an
      increased treatment of multi-rooted teeth.

PMID- 15479262
TI  - The radix entomolaris in mandibular first molars: an endodontic challenge.
AB  - AIM: To present cases of mandibular first molars with an additional distolingual
      root (radix entomolaris, RE) and to survey the literature on the incidence of
      this anatomical feature. SUMMARY: A major anatomical variant of the two-rooted
      mandibular first molar is a tooth with an additional distolingual and third root:
      the RE. The prevalence of these three-rooted mandibular first molars appears to
      be less than 3% in African populations, not to exceed 4.2% in Caucasians, to be
      less than 5% in Eurasian and Asian populations, and to be higher than 5% (even up
      to 40%) in populations with Mongolian traits. A total of 18 cases (12 root filled
      and six extracted mandibular first molars) with an RE were collected during the
      years 2000-2003 in patients of Caucasian origin. As far as the access was
      concerned, entering the root canal in the RE required a modification of the
      opening in a distolingual direction resulting in a trapezoidal opening cavity.
      None of the orifices was located midway between the mesial and distal root
      component. Based on the anatomy of the extracted samples and the bending of ISO
      10 files after scouting of the root canal in the RE, three types of curvature
      were detected: (I) straight or no curvature (two cases); (II) coronal third
      curved and straight continuation to the apex (five cases); and (III) curvature in
      the coronal third and buccal curvature from the middle third or apical third of
      the root (11 cases). KEY LEARNING POINTS: Clinicians should be aware of this
      unusual root morphology in mandibular first molars in Caucasian people.
      Radiographs exposed at two different horizontal angles are needed to identify
      this additional root. The access cavity must be modified in a distolingual
      direction in order to visualize and treat the RE, this results in a trapezoidal
      access cavity.

PMID- 15479263
TI  - Eating their way out of trouble: selective uptake of apoptotic eosinophils by
      bronchial epithelial cells.

PMID- 15479264
TI  - Impacts of climate change on aeroallergens: past and future.
AB  - Human activities are resulting in increases in atmospheric greenhouse gases, such
      as carbon dioxide, and changes in global climate. These, in turn, are likely to
      have had, and will continue to have, impacts on human health. While such impacts
      have received increasing attention in recent years, the impacts of climate change
      on aeroallergens and related allergic diseases have been somewhat neglected.
      Despite this, a number of studies have revealed potential impacts of climate
      change on aeroallergens that may have enormous clinical and public health
      significance. The purpose of this review is to synthesize this work and to
      outline a number of research challenges in this area. There is now considerable
      evidence to suggest that climate change will have, and has already had, impacts
      on aeroallergens. These include impacts on pollen amount, pollen allergenicity,
      pollen season, plant and pollen distribution, and other plant attributes. There
      is also some evidence of impacts on other aeroallergens, such as mould spores.
      There are many research challenges along the road to a more complete
      understanding of the impacts of climate change on aeroallergens and allergic
      diseases such as asthma and hayfever. It is important that public health
      authorities and allergy practitioners be aware of these changes in the
      environment, and that research scientists embrace the challenges that face
      further work in this area.

PMID- 15479265
TI  - Phagocytosis of apoptotic eosinophils but not neutrophils by bronchial epithelial
      cells.
AB  - BACKGROUND: We have previously demonstrated that human bronchial epithelial cells
      engulf apoptotic eosinophils. OBJECTIVES: To compare and contrast the phagocytic
      capabilities of monocyte-derived macrophage and primary airway epithelial cells
      for apoptotic granulocytes. RESULTS: Here we compared phagocytosis of human
      apoptotic eosinophils and neutrophils by small and large airway epithelial cells
      (SAEC and LAEC) and monocyte-derived macrophages. Confocal microscopy of F-actin
      staining and scanning and transmission electron microscopy revealed phagocytic
      cup formation around apoptotic eosinophils by airway epithelial cells (AEC)
      membranes with evidence of their digestion. Resting and cytokine-stimulated AEC
      did not recognize and ingest apoptotic neutrophils. The latter were phagocytosed
      by macrophages that exhibited greater ingestion of and higher capacity for,
      apoptotic eosinophils over apoptotic neutrophils. Cytochalasin D completely
      abolished uptake of apoptotic eosinophils by SAEC, LAEC or macrophage monolayers.
      Ligation of epithelial cell CD44 receptors for 24 h increased phagocytosis of
      apoptotic eosinophils by SAEC and LAEC with a potency comparable with that of IL
      1. Phagocytosis was a specific receptor-mediated process involving integrin-
      (alphavbeta3, alphavbeta5, CD36), phosphatidylserine receptor- and lectin
      dependent mechanisms. No significant differences were observed in avarice for
      apoptotic eosinophils by SAEC or LAEC either resting, CD44 monoclonal antibodies-
      or cytokine- stimulated, or in their usage and expression of recognition
      receptors. CONCLUSION: These findings further suggest and define an important
      role for the bronchial epithelium in the selective removal of apoptotic
      eosinophils from the airways in asthma.

PMID- 15479266
TI  - Non-anaphylactic surface-exposed peptides of the major birch pollen allergen, Bet
      v 1, for preventive vaccination.
AB  - BACKGROUND: Almost 100 million allergic patients are sensitized to the major
      birch pollen allergen, Bet v 1, a 17 kDa protein containing most of the IgE
      epitopes present in pollens of trees belonging to the Fagales order and plant
      derived food. OBJECTIVE: Our aim was to develop an approach for the rational
      design of B cell epitope-derived, non-allergenic peptide allergy vaccines.
      METHODS: According to the three-dimensional (3-D) structure of birch pollen
      allergen, Bet v 1, six peptides comprising 25-32 preferably solvent-exposed amino
      acids were synthesized. RESULTS: Because of lack of secondary structure, the
      peptides showed no allergenic activity in allergic patients. In a mouse model of
      birch pollen allergy, peptide vaccination induced Bet v 1-specific IgG and
      prevented IgE-mediated allergic sensitization to Bet v 1. The protective role of
      peptide-induced blocking antibodies is demonstrated by inhibition of allergic
      patients IgE binding to the allergen and by blocking of allergen-induced basophil
      degranulation. CONCLUSION: Our results indicate the mechanistic importance of
      blocking antibodies for allergy vaccination and present a B cell epitope-based
      approach for the rational design of safe peptide allergy vaccines whenever the
      structure of the disease-eliciting allergen is known.

PMID- 15479267
TI  - Food allergy and non-allergic food hypersensitivity in children and adolescents.
AB  - BACKGROUND: Previous studies have shown a 10-fold discrepancy of self-reported
      food-induced symptoms and physician-diagnosed food hypersensitivity. Little
      information is available on the prevalence of food hypersensitivity in unselected
      paediatric populations. No data were available for German children. OBJECTIVE: To
      study the perception of food-induced symptoms in the paediatric population, to
      investigate the allergens accused, to objectify patients' reports, and to
      identify subgroups at risk of having food-induced allergy (FA) or non-allergic
      food hypersensitivity (NAFH) reactions. METHODS: This paper presents the data of
      the paediatric group (0-17 years) of a representative, randomly sampled, cross
      sectional population-based survey studying 13 300 inhabitants of the German
      capital city Berlin regarding food-related symptoms. Instruments included mailed
      questionnaires, structured telephone interviews, physical examination, skin-prick
      tests, specific serum IgE and standardized, controlled and blinded oral food
      challenges. RESULTS: Two thousand three hundred and fifty-four individuals were
      contacted by mailed questionnaire, 739 (31.4%) responses could be fully
      evaluated. Four hundred and fifty-five (61.5%) participants reported symptoms
      related to food ingestion, 284 (38.4%) affirmed reproducible symptoms in the
      standardized telephone interview. One hundred and eighty-four (24.8%) individuals
      were fully examined. Reproducible symptoms to food were found in 31 (4.2%)
      children and adolescents: 26 (3.5%) showed symptoms of FA and five (0.7%) of
      NAFH. The oral allergy syndrome was most often observed. Foods most commonly
      identified by oral challenges were apple, hazelnut, soy, kiwi, carrot and wheat.
      CONCLUSION: The perception of food-related symptoms is common among children and
      adolescents from the general population. Self-reports could be confirmed in
      around one out of 10 individuals, still resulting in 4.2% of proven clinical
      symptoms. However, most reactions were mild and mainly because of pollen
      associated FA, while NAFH reactions were less common. Severe IgE-mediated FA was
      observed in individuals with pre-existing atopic disease, who should be fully
      investigated for clinically relevant FA.

PMID- 15479268
TI  - Ovalbumin-specific immunoglobulin G and subclass responses through the first 5
      years of life in relation to duration of egg sensitization and the development of
      asthma.
AB  - BACKGROUND: Egg sensitization, particularly persistent sensitization, is a risk
      factor for later asthma. However, little is known about accompanying IgG and
      subclass responses and how they might relate to asthmatic outcome. OBJECTIVE: To
      characterize hen's egg ovalbumin (OVA) IgG and subclass responses through the
      first 5 years of life in relation to duration of egg sensitization and later
      asthma. SUBJECTS AND METHODS: The subjects (n=46) formed part of a larger cohort,
      born to atopic parents, who had been evaluated prospectively for the development
      of asthma. Egg sensitization was classified as transient (positive egg skin prick
      test at 1 year only) or persistent (positive skin test for at least 2 years).
      Plasma OVA IgG, IgG1 and IgG4 concentrations at birth (cord), 6 months, 1 and 5
      years of age were measured by ELISA. RESULTS: The kinetics of OVA IgG and IgG1
      responses, but not IgG4, differed between egg sensitized and non-egg sensitized
      (NES) children. Only persistently sensitized children had a rise in OVA IgG1
      concentration through the first year of life, and at 1 year of age they had
      significantly higher OVA IgG and IgG1 than either transiently sensitized or NES
      children. High OVA IgG1 was associated with later asthma: at 1 year of age, OVA
      IgG1 greater than 14,500 U predicted asthma with a sensitivity 64% and
      specificity 74%. CONCLUSION: OVA IgG and subclass responses relate to the
      duration of egg sensitization. Measurement of OVA IgG1 concentration in infancy
      might offer a useful adjunct to identify those at an increased risk of asthma.

PMID- 15479269
TI  - Declining asthma prevalence in Hong Kong Chinese schoolchildren.
AB  - BACKGROUND: Many studies have reported an increase in the prevalence of asthma
      and related atopic disorders. The lack of standardized methodologies and
      'objective' measurements make reliable comparison and monitoring of trends of
      asthma very difficult. METHODS: In this study, a total of 3321 schoolchildren
      aged 13-14 years were recruited for study using the Phase III Protocol of the
      International Study of Asthma and Allergic disease in Childhood (ISAAC). The
      results were compared with those obtained in the Phase I ISAAC study (1994-95),
      which used the identical and validated core questionnaires. RESULTS: The
      prevalence rates of physicians' diagnosis of asthma were similar in the two
      surveys (11.2% and 10.2%), but the prevalence rates of wheeze (written
      questionnaire) in the past year have decreased from 12.4% in 1994-95 to 8.7% in
      2002 (P<0.001). For the video questionnaire, all asthmatic symptoms in the
      preceding 12 months were significantly lower in 2002 when compared with those in
      1994-95. Among the subjects with diagnosed asthma, the prevalence rates of wheeze
      in the past 12 months (written questionnaire) has decreased from 39.1% to 27.6%
      (P<0.001). The prevalence rates of having wheezing attack at least once per month
      (video questionnaire) has decreased from 10.5% to 5.6% (P=0.013). CONCLUSION:
      Using the same standardized and validated ISAAC questionnaire, the prevalence
      rates of asthma symptoms in Hong Kong Chinese schoolchildren have decreased since
      1994. The exact reasons for such trend remain to be explored.

PMID- 15479270
TI  - Self-reported prevalence and risk factors of asthma among Korean adolescents: 5
      year follow-up study, 1995-2000.
AB  - OBJECTIVES: The International Study of Asthma and Allergies in Childhood (ISAAC)
      questionnaires have shown that the prevalence of childhood asthma is increasing
      worldwide. Although Asian countries used to have lower prevalence rates of
      allergic disease than Western countries, this prevalence is increasing in several
      Asian countries. To determine whether the prevalence of childhood asthma is
      changing in Korean adolescents, we compared findings from nationwide cross
      sectional surveys in 1995 and 2000 on populations of middle-school children using
      the Korean version of the ISAAC questionnaire. METHODS: We developed Korean
      versions of the ISAAC written (WQ) and video (AVQ) questionnaires for allergic
      diseases. In 1995, the enrolled population consisted of 15,481 children, ages 12
      15, and encompassing all three grades in middle school, selected from 34 schools
      across the nation; the response rate was 97.3%. In 2000, 15,894 children were
      selected from 31 of the same schools, and the response rate was 96.4%. The SAS
      system version 8.0 was utilized for all statistical analyses. RESULTS: The WQ
      showed that the lifetime and 12-month prevalence of wheeze did not change from
      1995 to 2000. While the 12-month prevalence rates of sleep disturbed by wheezing
      and night cough increased, the rates of severe attack of wheezing and exercise
      induced wheeze did not change, over this period of time. The lifetime prevalence
      of asthma diagnosis, however, increased significantly, from 2.7% in 1995 to 5.3%
      in 2000, as did the 12-month prevalence of asthma treatment, from 1.0% in 1995 to
      1.9% in 2000. The AVQ also showed increases in the lifetime and 12-month
      prevalence rates of wheeze at rest, exercise-induced wheeze, nocturnal wheeze,
      nocturnal cough, and severe wheeze over this period of time. These were
      especially because of significant increases in the Provincial cities of Korea.
      Interestingly, the 12-month prevalence of wheeze was consistently high in Cheju
      with low air pollution indices, whereas this rate was low in Ulsan and Ansan with
      very high air pollution indices. Risk factor analysis showed that body mass index
      (BMI), passive smoking, and living with a dog or cat, but not air pollution, were
      associated with higher risk of wheeze. CONCLUSIONS: In the 5-year period from
      1995 to 2000, the prevalence of asthma symptoms has increased in Korean
      adolescents, much of it because of increases in Provincial Centers. BMI, passive
      smoking, and living with a dog or cat are important risk factors. Environmental
      factors other than air pollution may be associated with increases in asthma,
      especially in Provincial Centers.

PMID- 15479271
TI  - Dynamic changes in sensitization to specific aeroallergens in children raised in
      a desert environment.
AB  - BACKGROUND: Allergen skin test reactivity and total serum IgE are objective
      measures used to characterize and help diagnose allergic diseases. Cross
      sectional studies have shown that overall aeroallergen skin test reactivity
      increases throughout childhood. However, little attention has been paid to
      whether individual aeroallergen remittance occurs, which could distort or mask
      relationships to disease. OBJECTIVE: To access the incidence and remittance of
      skin test reactions to individual allergens in children aged 6-11 years. METHODS:
      Longitudinal sensitization to six aeroallergens and total IgE were assessed in
      828 children raised in the semi-arid US southwest at ages 6 and 11 years.
      RESULTS: New sensitization (to any allergen) between 6 and 11 years occurred in
      30.2% of children compared with 39.7% before age 6 years. The rate of complete
      remittance from positive to negative between ages 6 and 11 years was 8.2%, and
      total IgE at age 6 years was not predictive. Remittance rates for individual
      allergens were high and variable (19-49%). The perennial allergens Bermuda and
      Alternaria were early sensitizers and had low remittance rates. Early
      sensitization to the four seasonal allergens was less common and more subject to
      remittance with the bulk of sensitization occurring between 6 and 11 years.
      CONCLUSION: This study shows that sensitization to individual aeroallergens in
      childhood is dynamic and indicates the limitation of single point assessment of
      skin test reactivity.

PMID- 15479272
TI  - Haplotypes of the interleukin-4 receptor alpha chain gene associate with
      susceptibility to and severity of atopic asthma.
AB  - BACKGROUND: Development of asthma is likely to depend on a complex interaction
      between environmental and genetic factors. Several groups have suggested the gene
      of the IL-4 receptor alpha chain (IL4R) as a candidate gene for the development
      of asthma, although association with single polymorphisms has shown contradicting
      results. OBJECTIVE: We chose to analyse IL4R gene haplotypes and assess their
      possible relevance in susceptibility to asthma and to certain clinical
      phenotypes. METHODS: IL4R gene haplotypes were analysed, based on the three
      markers C-3223T, Q551R and I50V, using the expectation-maximization algorithm, in
      170 atopic asthma patients and 350 controls, all adult Swedish Caucasians.
      RESULTS: Our data showed significantly higher levels of soluble IL-4R (sIL-4R) in
      asthma patients compared with controls (P<0.0001). Furthermore, we showed a
      significant association between the IL4R haplotype containing the alleles T-3223,
      V50 and R551 (TVR) of the IL4R gene, and susceptibility to atopic asthma, with a
      frequency of 6.5% in the patients compared with 1% in the controls (P<0.0005). A
      subgroup of patients with heterozygous or homozygous state for the T-3223, V50
      and R551 alleles, also had lower levels of sIL-4R in their circulation compared
      with patients with homozygous state in the C-3223, I50 and Q551 alleles (P<0.05)
      and showed less severe asthma according to lung function test (P<0.05). Analysis
      of single markers showed the T-3223 IL4R allele to associate with lower serum
      levels of sIL-4 receptor (P<0.0001) and patients carrying the T allele also had
      more symptoms of active asthma (wheezing, P<0.01; coughing, P<0.05 and breathing
      difficulties, P<0.01). CONCLUSION: Our data suggest that asthmatic patients with
      low levels of sIL-4 receptor may represent a genetically distinct subgroup of
      atopic asthma. TVR haplotype analyses confirm the importance of IL4R as a
      candidate gene for susceptibility to asthma. This finding may have implications
      for the understanding of the pathogenesis of asthma and possibly for the
      development of more specific therapies.

PMID- 15479273
TI  - Assessment of recombinant dog allergens Can f 1 and Can f 2 for the diagnosis of
      dog allergy.
AB  - BACKGROUND: The use of recombinant allergens for the diagnosis and immunotherapy
      of allergy may offer several advantages over allergen extracts. OBJECTIVE: To
      produce recombinant dog allergens Can f 1 and Can f 2 in Pichia pastoris yeast
      and to assess their suitability for the diagnosis of dog allergy. METHODS:
      Clinically diagnosed dog-allergic patients' and healthy non-atopic dog owners'
      reactivities against recombinant Can f 1 and Can f 2 and commercial dog
      epithelial extract were studied by a panel of methods including skin prick test
      (SPT), ELISA and IgE immunoblotting. RESULTS: Recombinant Can f 1 and Can f 2
      were found immunologically functional: they bound dog-allergic patients' IgE in
      immunoblotting and inhibited specifically the binding of IgE to their natural
      counterparts in the dog allergen extract. Moreover, patients' IgE reactivity in
      immunoblotting to natural Can f 1 and their SPT with the recombinant allergen
      were perfectly concordant (phi coefficient 1.0, P<0.001). The concordance was
      slightly lower with recombinant Can f 2 (phi coefficient 0.92, P<0.001). A lower
      number of dog-allergic patients, 52%, reacted against Can f 1 than previously
      reported. About one-third of the patients reacted to Can f 2. In immunoblotting,
      the highest prevalence of reactivity, 60%, was directed to an 18 kDa component.
      Aminoterminal sequencing showed this to be a previously unidentified allergenic
      protein. CONCLUSIONS: The recombinant allergens can be used reliably to identify
      Can f 1 and Can f 2-sensitized individuals. However, the two allergens are
      insufficient as reagents for diagnosing dog allergy.

PMID- 15479274
TI  - Extensive in vitro cross-reactivity to seed storage proteins is present among
      walnut (Juglans) cultivars and species.
AB  - BACKGROUND: Tree nuts, including English walnuts (Juglans regia), are sources of
      food allergens often associated with life-threatening allergic reactions. It is
      unknown if seed storage proteins from other Juglans species have IgE epitopes
      similar to those of the important English walnut allergens, Jug r 1 (2S albumin)
      and Jug r 2 (vicilin-like). OBJECTIVE: To screen for potential germplasm sources
      of hypoallergenic seed storage proteins of relevance in walnut food allergy. We
      sought to identify English walnut cultivars (cvs) or other Juglans species that
      showed decreased IgE binding to major seed storage proteins or an inability to
      cross-react with Jug r 1 or Jug r 2. METHODS: We determined if IgE in sera of
      patients who have had life-threatening systemic reactions to English walnut bound
      protein extracts from all tested walnut cvs (57 cvs total) or species (six) by
      Western immunoblot. Further, we used immunoblot inhibition to determine the in
      vitro cross-reactivity of Jug r 1 and Jug r 2, native and recombinant, with
      several walnut species. RESULTS: All walnut cvs and species contain allergenic
      proteins. Furthermore, as shown by in vitro immunoblot inhibition, the major
      walnut allergens in the species tested cross-reacted with those in J. regia cv.
      Chandler and J. nigra cv. Thomas extracts. CONCLUSIONS: Based on our findings, it
      is unlikely that a composite hypoallergenic walnut could be bred from available
      germplasm. In addition, patients with severe allergy to English walnut are likely
      to be clinically allergic to all commercial English walnut cvs and other closely
      related Juglans species.

PMID- 15479275
TI  - Birch pollen rupture and the release of aerosols of respirable allergens.
AB  - BACKGROUND: Birch pollen allergens have been implicated as asthma triggers;
      however, pollen grains are too large to reach the lower airways where asthmatic
      reactions occur. Respirable-sized particles containing birch pollen allergens
      have been detected in air filters, especially after rainfall but the source of
      these particles has remained speculative. OBJECTIVE: To determine the processes
      by which birch pollen allergens become airborne particles of respirable size with
      the potential to contribute to airways inflammation. METHODS: Branches with
      attached male catkins were harvested and placed in a controlled emission chamber.
      Filtered dry air was passed through the chamber until the anthers opened, then
      they were humidified for 5 h and air-dried again. Flowers were disturbed by wind
      generated from a small electric fan. Released particles were counted, measured
      and collected for immuno-labelling and high-resolution microscopy. RESULTS: Birch
      pollen remains on the dehisced anther and can rupture in high humidity and
      moisture. Fresh pollen takes as long as 3 h to rupture in water. Drying winds
      released an aerosol of particles from catkins. These were fragments of pollen
      cytoplasm that ranged in size from 30 nm to 4 microm and contained Bet v 1
      allergens. CONCLUSION: When highly allergenic birch trees are flowering and
      exposed to moisture followed by drying winds they can produce particulate
      aerosols containing pollen allergens. These particles are small enough to deposit
      in the peripheral airways and have the potential to induce an inflammatory
      response.

PMID- 15479276
TI  - Self-reported drug allergy in a general adult Portuguese population.
AB  - AIM: To estimate the prevalence of self-reported drug allergy in adults. METHODS:
      Cross-sectional survey of a general adult population from Porto (all of whom were
      living with children involved in the International Study of Asthma and Allergies
      in Childhood-phase three), during the year 2002, using a self-administered
      questionnaire. RESULTS: The prevalence of self-reported drug allergy was 7.8%
      (181/2309): 4.5% to penicillins or other beta-lactams, 1.9% to aspirin or other
      non-steroidal anti-inflammatory drugs (NSAIDs) and 1.5% to other drugs. In the
      group 'allergic to beta-lactams', the most frequently implicated drug was
      penicillin G or V (76.2%) followed by the association of amoxicillin and
      clavulanic acids (14.3%). In the group 'allergic to NSAIDs', acetylsalicylic acid
      (18.2%) and ibuprofen (18.2%) were the most frequently identified drugs, followed
      by nimesulide and meloxicam. Identification of the exact name of the involved
      drug was possible in less than one-third of the patients, more often within the
      NSAID group (59.5%). Women were significantly more likely to claim a drug allergy
      than men (10.2% vs. 5.3%). The most common manifestations were cutaneous (63.5%),
      followed by cardiovascular symptoms (35.9%). Most of the reactions were
      immediate, occurring on the first day of treatment (78.5%). Only half of the
      patients were submitted to drug allergy investigations. The majority (86.8%)
      completely avoided the suspected culprit drug thereafter. CONCLUSIONS: The
      results showed that self-reported allergy to drugs is highly prevalent and poorly
      explored. Women seem to be more susceptible. beta-lactams and NSAIDs are the most
      frequently concerned drugs.

PMID- 15479277
TI  - Anaphylaxis to excipient mannitol: evidence for an immunoglobulin E-mediated
      mechanism.
AB  - BACKGROUND: Anaphylaxis to mannitol present naturally in pomegranate and
      cultivated mushroom in a sensitized subject has been described recently, and an
      IgE-mediated mechanism to this sugar alcohol has been proposed. The same subject
      also experienced severe allergic reactions to a chewable pharmaceutical
      (cisapride drug). OBJECTIVE: The purpose of the study was to identify allergenic
      component in the pharmaceutical preparation, and also, to understand the
      mechanism of immediate hypersensitivity to mannitol. METHODS: Methodology
      involved skin prick tests (SPTs), high-performance liquid chromatographic (HPLC)
      analysis of pharmaceutical preparations, separation of mannitol by Ca++-ion
      moderated cation-exchange chromatography, preparation of alditol-protein
      conjugates by reductive amination, SPT using the conjugates, hapten affinity
      purification of the allergic serum on D-mannitol-keyhole limpet haemocyanin (KLH)
      Sepharose CL-6B, and detection of serum mannitol-specific IgE by ELISA. RESULTS:
      Component testing by SPT, and HPLC analysis of various pharmaceuticals indicated
      that the excipient mannitol is the causative allergen. Mannitol separated from
      Cisapid MPS showed allergenic activity by SPT. Among the several conjugates
      tested by SPT, D-mannitol-bovine serum albumin and D-mannitol-KLH showed positive
      weal/flare reaction, demonstrating the presence of cell-bound mannitol-specific
      IgE in vivo. Negative results with D-glucitol, D-galactitol, meso-erythritol, and
      L-mannitol protein conjugates clearly showed that the mannitol-specific human IgE
      is very specific to the D-isomer of mannitol. ELISA using the hapten affinity
      purified allergic serum was positive, demonstrating the presence of mannitol
      specific serum IgE in the allergic subject. CONCLUSION: Mannitol, which is widely
      used as a food and drug additive (excipient), can rarely cause IgE-mediated
      anaphylaxis. This study is the first one to demonstrate the presence of mannitol
      specific human IgE in a sensitized allergic subject to validate an IgE-mediated
      hypersensitivity mechanism for mannitol.

PMID- 15479278
TI  - T-helper 2 cytokines attenuate senescent eosinophil activation by the CXCR4
      ligand stromal-derived factor-1alpha (CXCL12).
AB  - BACKGROUND: Different chemokine receptors have been suggested to play a pivotal
      role in allergic diseases and therefore to be relevant for the activation of
      effector cells and propagation of the inflammatory response. The CXC chemokine
      receptor CXCR4 has recently been found on the surface of eosinophils implicating
      a role in allergic diseases. OBJECTIVE: The aim of this study was to investigate
      the functional expression of CXCR4 on senescent eosinophils. Moreover, we
      questioned whether the cytokine profile--T-helper (Th)1 and Th2 cytokines--affect
      the activation of eosinophils via the CXCR4 that could be important for the
      different phases of the allergic reaction. METHODS: CXCR4 expression on human
      eosinophils was analysed by flow cytometry and RT-PCR. Functional analyses of
      intracellular calcium fluxes, actin polymerization, release of reactive oxygen
      species and, chemotaxis were carried out using spectrofluorometry, flow
      cytometry, chemiluminescence and modified Boyden chamber technique. RESULTS:
      Whole blood and freshly isolated eosinophils weakly express CXCR4 surface
      protein. Incubation in culture medium without addition of cytokines for 24 h
      always lead to strong CXCR4 surface expression that paralleled with stromal
      derived factor-1alpha (CXCL12)-induced eosinophil activation. Stimulation of
      eosinophils with CXCL12 leads to an internalization of CXCR4, which could be
      prevented by phenylarsine oxide. Co-incubation of eosinophils with Th2 cytokines
      such as IL-3, IL-4, IL-5, IL-13, and granulocyte macrophage-colony stimulating
      factor prevented the expression of CXCR4 and affected eosinophil activation after
      stimulation with the CXCR4 ligand CXCL12. From these cytokines, IL-3 was the only
      cytokine completely inhibited intracellular calcium fluxes and chemotaxis of
      eosinophils in response to CXCL12. CONCLUSION: Senescent eosinophils express
      functional CXCR4 receptors, which are prevented by Th2 cytokines that are found
      in the early phase of allergic reaction. Therefore, CXCR4 activation of
      eosinophils seems to be important in the chronic phase of allergic reaction,
      which is dominated by a Th1 cytokine profile.

PMID- 15479279
TI  - Red blood cells regulate eosinophil chemotaxis by scavenging RANTES secreted from
      endothelial cells.
AB  - BACKGROUND: Eosinophils play a critical role in the pathogenesis of allergic
      diseases. CC chemokines, such as regulated on activation, normal, T cell
      expressed, and secreted (RANTES), are key regulators of eosinophil locomotion.
      Although eosinophils migrate from the bloodstream into tissues, mechanisms that
      generate a chemogradient across the endothelium remain to be fully elucidated.
      OBJECTIVE: We first examined the polar secretion of RANTES by endothelial cells.
      We also studied the functional scavenging effect of red blood cells (RBCs) on
      RANTES secreted into the intravascular side. METHODS AND RESULTS: Endothelial
      cells were cultured in a transwell chamber with a membrane pore size of 0.45,
      3.0, and 8.0 microm and stimulated with TNF-alpha, IL-1beta, or IFN-gamma from
      the apical or basolateral side for 16 h. The measurement of RANTES in the
      supernatant was performed by ELISA. We did not see any difference in the amount
      of RANTES secreted from the cytokine-stimulated endothelium between inner
      (intravascular side) and outer (extravascular side) wells separated by the 8.0
      microm membrane, although apical polarization was observed with the 0.45-microm
      membrane. The addition of RBCs (hemoglobin (Hb): 0.5-15 g/dL) to the apical
      supernatant of TNF-alpha-stimulated endothelial cells reduced the RANTES level in
      a concentration-dependent manner. The treatment of supernatant on the
      intravascular side with RBCs significantly enhanced the migration of eosinophils.
      CONCLUSION: RBCs possess a scavenging effect on intravascular RANTES, and thereby
      regulate transendothelial migration of eosinophils. Our findings suggest a new
      role of RBCs in allergic inflammation.

PMID- 15479280
TI  - Smooth muscle hypertrophy in distal airways of sensitized infant rhesus monkeys
      exposed to house dust mite allergen.
AB  - BACKGROUND: Airway smooth muscle hypertrophy is closely associated with the
      pathophysiology of hyper-reactive airways in allergic asthma. OBJECTIVE: To
      determine whether repeated exposure to allergens during postnatal lung
      development promotes remodelling of airway smooth muscle. METHODS: Infant, male
      rhesus monkeys (30-day-old) were sensitized to house dust mite allergen (HDMA)
      and then exposed to HDMA aerosol periodically over 5 months. Smooth muscle mass
      and bundle size and abundance in conducting airways were measured and compared
      with age-matched control (filtered air-exposed) monkeys. RESULTS: Total smooth
      muscle mass and average bundle size were significantly greater in the conducting
      airways of monkeys exposed to HDMA. Smooth muscle bundle abundance was not
      affected by exposure to HDMA. CONCLUSION: Repeated cycles of allergen exposure
      alter postnatal morphogenesis of smooth muscle, affecting both total mass and
      bundle size, in conducting airways of infant monkeys.

PMID- 15479281
TI  - Mould extracts increase the allergic response to ovalbumin in mice.
AB  - BACKGROUND: Exposure to moulds in indoor air is thought to induce asthma in
      susceptible persons. Moulds may contain several potent allergens. However, more
      importantly, moulds may increase the allergic response to other allergens
      (adjuvant effect). Previously, we have found that a beta-1,3-glucan from the cell
      wall of the fungus Sclerotinia sclerotiorum increases the allergic response to
      the model allergen ovalbumin (OVA) in a mouse model. OBJECTIVE: In the present
      study, we wanted to confirm the adjuvant effect of another beta-1,3-glucan,
      MacroGard (MG) from baker's yeast in this model. More importantly, we wished to
      explore the putative effects of extracts from the moulds Cladosporium herbarum
      (CH) and Penicillium chrysogenum (PC) using the very same model as used to
      explore effects of beta-glucans. METHODS: Groups of eight Balb/c mice were
      injected with OVA alone, OVA+extract or OVA+MG, into one footpad. On day 21, all
      mice were reinjected with OVA, before exsanguination on day 26. The levels of OVA
      specific IgE, IgG1 and IgG2a in serum were measured by ELISA. RESULTS: Compared
      with OVA alone, OVA+MG, OVA+CH extract and OVA+PC extract increased OVA-specific
      IgE and IgG1 levels significantly. For all groups, the levels of IgG2a anti-OVA
      remained similar to those of the OVA-alone group. CONCLUSIONS: Our results show
      that extracts from CH and PC, and the beta-1,3/1,6-glucan from baker's yeast have
      adjuvant effects on the allergic response in mice.

PMID- 15479282
TI  - Allergen-specific immunosuppression by ovalbumin fused with diphtheria toxin in
      mice sensitized with albumins of different origin.
AB  - BACKGROUND: We previously reported that ovalbumin-diphtheria toxin (OVA-DT)
      fusion protein eliminates mast cells bearing OVA-specific IgE and protects OVA
      sensitized mice from fatal anaphylaxis induced by OVA challenge. OBJECTIVE: To
      prove the specificity of therapeutic effect of OVA-DT to allergy induced by OVA
      only and not by other allergens such as human serum albumin (HSA), and to examine
      the cytotoxic effect of OVA-DT on B cells bearing OVA-specific IgE. METHODS: Mice
      were sensitized with two different antigens, OVA and HSA, and then treated with
      OVA-DT. The therapeutic effect of OVA-DT on the allergy response to each of
      allergen was evaluated by anaphylactic test. The effect of OVA-DT on the
      production of allergen-specific Ig isotypes of the sensitized mice and the
      cytotoxic effect of OVA-DT on B cells expressing OVA-specific IgE were examined.
      RESULTS: OVA-DT suppressed only OVA-induced allergy but not HSA-induced allergy
      in mice sensitized with a mixture of OVA and HSA. The suppression was prolonged
      even to the mice boosted with the same allergen 14 days after last treatment of
      OVA-DT. In addition, when the sensitized mice were boosted with the same
      allergens 14 days after last treatment of OVA-DT, the mice showed to increase the
      production of OVA-specific IgG2a/IgG3 and decreased that of OVA-specific IgE. OVA
      DT targeted B cells bearing OVA-specific IgE, and killed them by DT-mediated
      cytotoxicity. CONCLUSION: The therapeutic effect of OVA-DT was specific to OVA
      induced allergy and the suppression of OVA-induced allergy was continuously shown
      in the mice boosted with the same allergens. This is considered to be caused by
      the increase of OVA-specific IgG2a and IgG3, and because of the decrease of OVA
      specific IgE by killing of B cells bearing OVA-specific IgE.

PMID- 15479283
TI  - Desloratadine partially inhibits the augmented bacterial responses in the sinuses
      of allergic and infected mice.
AB  - BACKGROUND: Allergic rhinitis (AR) is considered a major predisposing factor for
      the development of acute bacterial rhinosinusitis. How AR augments a bacterial
      infection is unknown. OBJECTIVE: Our purpose in this study was to test whether an
      H1 receptor antagonist, desloratadine, could reduce the augmented effect of an
      ongoing allergic reaction on acute bacterial rhinosinusitis. METHODS: Three
      groups of infected and ovalbumin (OVA)-sensitized mice were studied: (1) infected
      and allergic mice treated with desloratadine, (2) infected and allergic mice
      treated with placebo, and (3) infected mice. A fourth group of uninfected, non
      sensitized mice served as a control for the cellular changes. BALB/c mice were
      sensitized by two intraperitoneal injections of OVA given 8 days apart. One day
      after the second injection, the mice were nasally exposed daily to 6% OVA (the
      groups treated with desloratadine or placebo) or phosphate-buffered saline (PBS)
      (the infection-only group) for 5 days. After the second OVA exposure, the mice
      were intranasally inoculated with Streptococcus pneumoniae. Desloratadine or
      placebo was given daily throughout the OVA exposure period. Nasal allergic
      symptoms were observed by counting of nasal rubbing and sneezing for 10 min after
      OVA or PBS nasal challenge. On day 5 post-infection, nasal lavage culture was
      done, and the inflammatory cells in the sinuses were evaluated by flow cytometry.
      RESULTS: Mice that were made allergic, infected, and treated with placebo showed
      more organisms and phagocytes than did only infect mice. They also manifested
      allergic nasal symptoms and eosinophil influx into the sinuses. Desloratadine
      treatment during allergen exposure reduced allergic symptoms and reduced
      sinonasal infection (P<0.05). There tended to be less myeloid cell and neutrophil
      influx (P=0.09 both), but not eosinophil influx (P=0.85) compared with that in
      the placebo-treated group. CONCLUSION: Desloratadine treatment during nasal
      challenge inhibited allergic symptoms and reduced sinonasal infection, suggesting
      that histamine via an H1 receptor plays a role in the augmented infection in mice
      with an ongoing allergic reaction.

PMID- 15479284
TI  - Spoke-wheel-like enhancement as an important imaging finding of chromophobe cell
      renal carcinoma: a retrospective analysis on computed tomography and magnetic
      resonance imaging studies.
AB  - AIM: Little information has been reported with regard to the radiological
      features of chromophobe cell renal carcinomas (CCRC). The aim of the present
      study was to identify imaging characteristics which lead to the histological
      diagnosis of CCRC. METHODS: The imaging findings of computed tomography (CT) and
      magnetic resonance imaging (MRI) were retrospectively analyzed in 11 patients
      with CCRC operated on at Tokyo Women's Medical University, Tokyo, Japan. RESULTS:
      None of the factors studied were significant in distinguishing the two variants,
      typical and eosinophilic variants. Enhanced CT scans showed a spoke-wheel-like
      enhancement with a central scar in 3 patients (27%). The radiological patterns
      were classified into two groups. Seven patients (64%) showed pattern 1 in which:
      (i) a hypodense to isodense enhancement compared to the renal medulla in the
      corticomedullary phase during dynamic CT; (ii) an isodense mass compared to the
      renal medulla in unenhanced CT scan; and (iii) a lobulated appearance were
      typically observed. Four patients (36%) showed pattern 2 that seemed to be
      similar to the features of clear cell carcinoma, having an alveolar structure
      including a hyperdense enhancement in the corticomedullary phase and an
      inhomogeneous appearance. A spoke-wheel-like enhancement was observed only in
      patients with pattern 1, and was more clearly demonstrated in larger tumors.
      CONCLUSIONS: The CT and MRI findings in CCRC patients were not uniform, but it
      was noted that a spoke-wheel-like enhancement with a central stellate scar, which
      might have been mistaken for oncocytoma, was one of important findings of CCRC.
      Tumors demonstrating a spoke-wheel-like enhancement with a central scar should be
      carefully managed, because they could be malignant.

PMID- 15479285
TI  - Influence of pretransplant dialysis modality on the change of lymphocyte subset
      populations and acute rejection rates after renal transplantation.
AB  - BACKGROUND: The influence of dialysis modality on the acute rejection (AR) rate
      after renal transplantation is controversial. We investigated whether the
      pretransplant dialysis modality correlated with the lymphocyte subset populations
      and the incidence of AR after renal transplantation. METHODS: Thirty-eight first
      living renal transplant recipients, consisting of 22 patients on pretransplant
      hemodialysis (HD) and 16 patients on pretransplant peritoneal dialysis (PD), were
      studied. Peripheral blood samples were taken on days -1 through 28 after
      transplantation, and the lymphocyte fractions were exposed to the monoclonal
      antibodies anti-CD3, CD19, CD4, CD8 and CD28 for a flow cytometer analysis.
      Biopsy specimens were obtained at the time of presumed AR episodes and on day 28
      after transplantation. RESULTS: The PD patients had a higher frequency of AR
      (37.5% in PD vs 9.1% in HD patients, P = 0.034). In contrast, two HD patients
      showed graft loss at 18 and 30 months after transplantation. The increases of
      CD3, CD19, CD4 and CD4+ CD28+ cells in the PD patients occurred earlier than in
      the HD patients and the numbers of these cells in the PD group were higher than
      those in the HD between days 3-28 after transplantation, most significantly on
      day 7. CONCLUSIONS: These findings suggest that the PD patients with similar
      clinical characteristics could potentially have a higher immunocompetence and
      immune responsiveness associated with a higher rate of AR in the early stage of
      renal transplantation when compared with the HD patients.

PMID- 15479286
TI  - Stones in anomalous kidneys: results of treatment by shock wave lithotripsy in
      150 patients.
AB  - OBJECTIVE: To determine the efficacy of shock wave lithotripsy (SWL) in anomalous
      kidneys. METHODS: From October 1990 to October 2002, 150 patients (93 men and 57
      women) with anomalous urinary tracts, including 45 horseshoe kidneys, 57 duplex
      kidneys, 30 malrotated kidneys, 14 pelvic and four crossed ectopic kidneys were
      treated with SWL for urolithiasis at the Gazi University Faculty of Medicine.
      Shock wave lithotripsy was performed with Siemens Lithostar plus (Siemans,
      Erlanger, Germany) device and all procedures were carried under fluoroscopic
      control. RESULTS: The mean shock wave number and intensity received by the
      patients was 3770 (range, 1380-4100) shocks and 18.4 (range, 16.1-19) kV per
      session, respectively. The minimum success rate was obtained in patients with
      lower calyceal (50%) followed by middle calyceal (60%) calculi. The stone-free
      rate decreased and the number of sessions per patient increased with increasing
      stone diameter (dm). In patients with a stone dm > 30 mm, only 34% could be stone
      free, compared to a rate of 92% for calculi dm < 10 mm. The overall stone free
      rate at the third month was 68%. The best stone-free rates were obtained in
      patients with ureteral duplication (80.7%). The stone-free rates in horseshoe,
      malrotated, pelvic and crossed ectopic kidneys were found to be 66.7%, 56.7%,
      57.2% and 25%, respectively. CONCLUSION: Shock wave lithotripsy might be an
      effective and minimally invasive treatment alternative in stone-bearing anomalous
      kidneys. The type of anomaly, stone burden and localization seem to be the main
      parameters effecting the treatment success.

PMID- 15479287
TI  - Expression of nitric oxide and inducible nitric oxide synthase in acute renal
      allograft rejection in the rat.
AB  - BACKGROUND: Recent studies have shown that nitric oxide (NO) synthases,
      particularly inducible nitric oxide synthase (i-NOS), are induced in acute
      rejection episodes following heart, liver, pancreas and kidney
      allotransplantation. Furthermore, tissue and cellular injury has been
      demonstrated to be mediated by peroxynitrite (ONOO-), a metabolite of NO as well
      as a potent oxidant. However, a detailed relationship between NO, i-NOS and graft
      injury in transplantation remains elusive. METHODS: The present study used the
      following models of renal transplantation in rats: allografts (n = 5, Brown
      Norway to Lewis [LEW] rats), isografts (n = 5, LEW to LEW) and allografts treated
      with aminoguanidine (AG), an i-NOS inhibitor (n = 5). Blood urea nitrogen (BUN),
      serum creatinine (SCr) and urinary and serum nitrosocompounds (NOx) were measured
      on days 2, 4 and 7 post-transplant. Western blot analysis of i-NOS protein
      expression and measurement of i-NOS activity were carried out in grafts harvested
      on Day 7, along with immunohistochemical and histopathological examinations.
      RESULTS: In the allograft group, both BUN and SCr levels increased markedly on
      Day 7, in parallel with a sharp increase in NOx. A band stained by anti-i-NOS
      antibody was detected at approximately 130 kDa, along with high levels of i-NOS
      activity and diffusely distributed i-NOS-positive cells (macrophages).
      Histologically, an acute rejection episode was confirmed (Grade 3 according to
      Banff classifications). In the AG group, reduced renal function and graft injury
      were significantly less severe than in the allograft group. CONCLUSIONS: In rat
      renal allograft acute rejection, markedly increased levels of serum NOx were
      observed, along with enhanced tissue i-NOS activity, together resulting in graft
      injury. AG administration suppressed the increase of serum NOx levels, with
      concomitant mitigation of tissue injury and renal function impairment.

PMID- 15479288
TI  - Can normal saline be used to fill the balloon of a Foley catheter? The experience
      of a prospective randomized study in China.
AB  - BACKGROUND: Despite the lack of evidence, using normal saline for inflating the
      balloon of a Foley urethral catheter is frequently regarded as a cause for
      deflation failure. We have investigated the issue by comparing the rate of
      deflation failure of Foley catheter balloon, using either sterile water or normal
      saline as the filling solution. METHODS: Four thousand latex Foley urethral
      catheters (14 Fr) were randomly assigned to one of two groups: sterile water or
      normal saline. Each of the catheter balloons would then be inflated with 10 mL of
      the corresponding fluid. They were subsequently put in water baths at 37 degrees
      C for 4 weeks. At the end of 4 weeks, all the balloons were deflated by people
      who were blind to the assignment of fluid inflated. Failure of deflation was
      defined as the balloon not being able to be deflated completely. The number of
      deflation failures was recorded and the amount of fluid aspirated from each
      balloon was also noted. RESULTS: Of the 4000 catheters, 17 (0.43%) were found to
      be defective and could not be used for the study. The remaining 3983 catheters
      were randomly allocated into the sterile water (2011) and normal saline (1972)
      groups. The failure rate of deflation for the sterile water group and normal
      saline group were 185 (9.2%) and 157 (8.0%), respectively, which was not
      statistically significant (P = 0.162). CONCLUSION: There was no difference in the
      rate of deflation failure of latex Foley balloons by using either sterile water
      or normal saline as the filling solution.

PMID- 15479289
TI  - Effect of treating lower urinary tract symptoms on anxiety, depression and
      psychiatric morbidity: a one-year study.
AB  - BACKGROUND: The present study aimed to evaluate the effects of treating lower
      urinary tract symptoms (LUTS) on anxiety, depression and psychiatric morbidity
      following one year of follow-up. METHODS: A total of 297 patients were involved
      in this study. Patients were recruited into a surgical group (patients underwent
      transurethral resection of the prostate, n = 111), a medical group (underwent
      alpha-blockers treatment, n = 116) and a control group (renal stones patients
      with no or mild symptoms of severity, n = 70). Patients were assessed on anxiety,
      depression and psychiatric morbidity levels before and after treatment and were
      followed at 3, 6 and 12 months. RESULTS: The study showed that before treatment
      for LUTS, most of the patients, especially the surgical group compared to the
      medical and control groups, were more anxious, depressed and psychiatrically
      morbid. However, after treatment, most of the patients in the surgical group
      experienced a great improvement in their anxiety, depression and psychiatric
      morbidity level when compared to the medical and control groups. The reduction or
      improvement of their psychological profile was due to the reduction or total
      withdrawal of LUTS after treatment. CONCLUSION: Both medical and surgical
      treatment improved patient LUTS and thus improved their overall anxiety,
      depression and psychiatric morbidity.

PMID- 15479290
TI  - Prostate-specific antigen doubling time among Japanese men in an annual health
      screening program.
AB  - BACKGROUND: Prostate-specific antigen doubling time (PSA-DT) has been studied as
      a parameter reflecting the biological doubling rate of clinically localized
      prostate cancer treated expectantly. With the use of PSA-DT, we studied the
      natural history of PSA changes among Japanese men in a health screening program.
      METHODS: Between July 1994 and December 2002, a cohort of 1995 men aged 40-79
      years underwent a total of 5700 PSA measurements in an annual multiphasic health
      screening program. Prostate-specific antigen doubling time was calculated using a
      log-linear regression model for 994 (49.8%) men who had three or more serial PSA
      measurements with a mean follow-up of 46.2 months. RESULTS: Of the 994 men, 192
      (19.3%) had a PSA-DT of less than 10 years and 12 (1.2%) had a PSA-DT of less
      than 2 years. Median PSA-DT in 14 men with a subsequent diagnosis of prostate
      cancer was 41.6 months (range, 12.2 to stable). A log-linear model statistically
      fitted 65 of 180 non-cancer patients with a PSA-DT of less than 10 years. The
      percentages of statistically fit cases increased with higher baseline PSA (5.3%,
      7.7% and 8.7% among men with <1.0, 1.0-1.99 and 2.0-3.99 ng/mL, respectively) and
      older baseline age (3.7%, 8.5% and 6.9% among ages 40-49, 50-59 and 60 or older,
      respectively). CONCLUSION: In a small but significant portion of men, PSA
      increases exponentially when it is still less than 4.0 ng/mL, with a PSA-DT of
      less than 10 years. The clinical significance of this finding should be evaluated
      by a prospective screening including biopsy.

PMID- 15479291
TI  - Long-term survival following radical prostatectomy in Japanese men with
      clinically localized prostate cancer: a single institutional study.
AB  - BACKGROUND: We evaluated the outcome of radical prostatectomy to provide
      information about long-term survival following this procedure. METHODS: One
      hundred and twenty-three otherwise healthy Japanese patients with clinically
      localized tumors underwent radical prostatectomy. Treatment outcomes were
      measured in terms of clinical progression-free survival, prostate cancer-specific
      survival and overall survival. Overall survival was compared with expected
      survival of age-matched Japanese men. RESULTS: For these 123 patients, clinical
      progression-free survival and prostate cancer-specific survival at 10 years were
      72.5% and 86.4%, respectively. Results of Cox multivariate analysis showed that
      only pathological stage (P = 0.047) and tumor grade (P = 0.009) were independent
      predictors of clinical progression. Only tumor grade was a statistically
      significant independent predictor (P = 0.048) in terms of prostate cancer death.
      Both the 10 and 15-year overall survival rates for these 123 patients were 58.6%,
      whereas the expected survival of age-matched Japanese men was 65.0% at the 10
      year follow up, and 43.8% at the 15-year follow up. CONCLUSIONS: The long-term
      overall survival in this surgically treated group is comparable to the expected
      survival rate of age-matched Japanese men. These results might be useful in
      counselling patients with clinically localized prostate cancer.

PMID- 15479292
TI  - Long-term treatment outcome of tamsulosin for benign prostatic hyperplasia.
AB  - BACKGROUND: The present study assessed the long-term efficacy (>12 months) of
      tamsulosin in 123 patients with lower urinary tract symptoms caused by benign
      prostatic hyperplasia (BPH). METHODS: The patients received a starting dose of
      tamsulosin of 0.2 mg/day, with a further titration up to 0.4 mg/day until symptom
      relief. Subjective and objective clinical variables were assessed using the
      international prostate symptom score (IPSS), IPSS quality of life (QoL) score,
      BPH impact index score, peak urinary flow rate (Q(max)) and postvoid residual
      urine volume. RESULTS: Except for Q(max), all clinical variables showed
      significant sustained improvements from baseline throughout the study period
      (median follow up, 43 months). Thirty patients (24.4%) withdrew because of
      surgical interventions. The Cox proportional hazards model showed that a baseline
      IPSS total score >or=15 (HR [hazard ratio] 2.13; 95% CI 1.04-4.34) was predictive
      of failure for tamsulosin therapy. Furthermore, during the first 12 months, a
      lowest IPSS total score >or=13 (HR 2.34; 95% CI 1.12-4.89), a lowest IPSS QoL
      score >or=3 (HR 4.16; 95% CI 1.26-13.68), and a lowest BPH impact index score
      >or=4 (HR 3.54; 95% CI 1.62-7.75) were also predictive of failure for tamsulosin
      therapy. CONCLUSIONS: Tamsulosin treatment of BPH patients for more than 12
      months showed a sustained, stable efficacy. Patients without short-term effects
      were prone to withdraw from tamsulosin therapy, but so did patients with a high
      baseline IPSS total score, even if therapy was effective for at least 12 months.

PMID- 15479293
TI  - Proliferation of DU145 prostate cancer cells is inhibited by suppressing insulin
      like growth factor binding protein-2.
AB  - BACKGROUND: Insulin-like growth factor binding protein-2 (IGFBP-2) is expressed
      by all human prostate cancer cell lines and dramatically increases in the serum
      of prostate cancer patients. However, the role of IGFBP-2 in prostatic
      tumorigenesis is not known. The aim of the present study was to investigate the
      effects of IGFBP-2 on the proliferation of DU145 human prostate cancer cells in
      culture. METHODS: Using cell proliferation assays, we examined the effects of
      exogenously administered and endogenously modulated levels of IGFBP-2 on the
      proliferation of DU145 cells. RESULT: Cell growth was stimulated by exogenously
      administered IGFBP-2, but significantly retarded (P < 0.05) by its neutralizing
      antibody. Overexpression of IGFBP-2 by transfection also stimulated cell growth,
      which was significantly (P < 0.05) inhibited in transfectants expressing
      antisense mRNA to IGFBP-2. Furthermore, the proliferation of IGFBP-2
      overexpressing cells was significantly dampened by exogenously administered IGFBP
      2 antibody. CONCLUSIONS: IGFBP-2 is an autocrine growth factor for DU145 human
      prostate cancer cells and cell proliferation can be significantly retarded by
      neutralizing or inhibiting its synthesis. These findings provide a strong
      rationale for targeting IGFBP-2 in the testing of novel strategies to treat
      prostate cancer.

PMID- 15479294
TI  - Non-invasive estimation of intraurethral pressure profile from uroflowmetric
      curve.
AB  - BACKGROUND: An intraurethral pressure-time profile as urodynamic information was
      obtained in a non-invasive manner using an equivalent equation as a voiding
      model. METHODS: The reasonability of the voiding model was confirmed by applying
      it to an experimental flow curve likened to urinary flow. The flow curve was
      approximated and the pressure profile was estimated. From the uroflowmetric
      curves obtained in a normal subject and a patient with bladder outlet
      obstruction, the respective intraurethral pressure profiles were estimated.
      RESULTS: The pressure profile estimated from the approximated flow curve was
      found consistent with the profile of the difference between the pressure actually
      measured at two different portions in the experimental system. CONCLUSION: Non
      invasive estimation of intraurethral pressure profile from uroflowmetric curves
      may be very useful to grasp intraurethral urodynamic information in clinical
      practice.

PMID- 15479295
TI  - Clinical features of testicular tumors in children.
AB  - AIM: Testicular tumors are not common pediatric solid tumors, especially in Asian
      children. There have been few reviews of cases in Japan to date. We present the
      clinical features of 14 pediatric testicular tumor patients. METHODS: Clinical
      features of 14 testicular tumor patients, such as chief complaints, age at
      diagnosis, pathology, stages, treatments and prognosis, were examined from
      medical records. Two patients had their semen tested at adolescence. RESULTS: Of
      the 14 prepubescent patients, 12 (85.7%) patients were diagnosed before 3 years
      of age. Ten cases (71.4%) were diagnosed as yolk sac tumors, three (21.4%) as
      mature teratomas and one case as an epidermoid cyst. Nine cases (90.0%) among the
      10 cases of yolk sac tumor were diagnosed as stage I and one case was stage IV.
      One stage I yolk sac tumor patient developed lung metastasis later. Eventually,
      two yolk sac tumor patients died, despite chemotherapy. While all the cases with
      a diagnosis before 2 years of age survived, 67% (2/3) of cases with a diagnosis
      after the age of 2 died of tumors. Semen analysis in two patients showed
      normospermia. CONCLUSION: In the present study, the most common testicular tumors
      were yolk sac tumors and the patients diagnosed before 2 years of age showed
      favorable results. Age could be a relapse risk factor in yolk sac tumors.
      Guidelines for handling testicular tumors in children is not yet well established
      in Japan. An organized system seems necessary to gather and accumulate the
      results of the cases in Japan in order to develop better guidelines for
      treatment.

PMID- 15479296
TI  - Solitary metastasis of renal cell carcinoma to the parotid gland 10 years after
      radical nephrectomy.
AB  - Renal cell carcinoma metastasis to the parotid gland after tumor nephrectomy is
      extremely rare. We report a case of solitary parotid metastasis from clear cell
      renal cell carcinoma in a 59-year-old woman, who presented 10 years after primary
      treatment. To our knowledge this is the first case in the published literature
      presenting with solitary parotid metastasis after such a long time. Superficial
      parotidectomy with preservation of the facial nerve was performed. One year
      after, the patient developed contralateral multiple kidney tumors and underwent
      left radical nephrectomy. She is currently on a dialysis program and no
      additional metastasis has been observed for 18 months.

PMID- 15479297
TI  - Angiomyolipoma of kidney involving the inferior vena cava.
AB  - We successfully treated a case of angiomyolipoma of the right kidney involving
      the inferior vena cava. Tissue sections of the tumor were immunostained and
      immunohistochemically tested with the smooth muscle related antibodies, namely,
      calponin h1, h-caldesmon and alpha-smooth muscle actin, and were then compared
      with the five cases of common type of angiomyolipoma. Furthermore, we reviewed
      and analyzed 25 case reports of invasive renal angiomyolipomas.

PMID- 15479298
TI  - Traumatic renal artery thrombosis with renovascular hypertension.
AB  - A 15-year-old boy, who tumbled from a fourth-floor window, was transported to our
      hospital. Enhanced computed tomography (CT) 1.5 h after the injury showed a non
      contrasted right kidney, and a repeat CT 6 h after the injury showed a growing
      retroperitoneal hematoma. The angiography showed complete obstruction of the
      right renal artery and bleeding from the subcapsular artery, which was
      successfully embolized. Renovascular hypertension developed on the second day
      after the injury; therefore, simple nephrectomy was performed.

PMID- 15479299
TI  - Progressive anemia following combination therapy with interferon-alpha and
      interleukin-2 in a patient with metastatic renal cell carcinoma.
AB  - Various toxicities have been observed during the treatment of advanced renal cell
      carcinoma with interferon-alpha (IFN-alpha) and/or interleukin-2 (IL-2). We
      report a case of severe anemia, which responded well to steroid therapy, in a
      patient receiving IL-2 plus IFN-alpha for metastatic renal cell carcinoma.

PMID- 15479301
TI  - Primary carcinoid tumor arising in a retroperitoneal mature teratoma in an adult.
AB  - An extremely rare case of a primary carcinoid tumor arising in a mature
      retroperitoneal teratoma is reported. A 53-year-old woman was admitted for
      further examination of an incidental retroperitoneal mass with calcification.
      Computed tomography scans demonstrated a tumor with fat, soft tissue and bone
      densities on the left renal hilum. Surgical excision of the tumor was performed
      with a preoperative diagnosis of retroperitoneal teratoma. The pathological
      diagnosis was mature teratoma, including all three germ layers. A carcinoid tumor
      was evident among teratoid tissues and it was thought to be a teratoma with
      malignant transformation. The patient did not have a carcinoid syndrome and had
      an uneventful recovery. She has been followed for 31 months with no recurrence.
      Carcinoid tumors rarely occur in teratomas of the ovary and the testis and, to
      our knowledge, this is the first case of carcinoid arising in a retroperitoneal
      mature teratoma.

PMID- 15479300
TI  - Pneumomediastinum and subcutaneous emphysema as the manifestation of
      emphysematous pyelonephritis.
AB  - Pneumomediastinum, a collection of mediastinal air, often results from the
      rupture of intrathoracic structures. A 41-year-old diabetic woman initially
      presented with signs of pneumomediastinum and nuchal subcutaneous emphysema, but
      was finally diagnosed with unilateral emphysematous pyelonephritis.
      Pneumomediastinum as a presentation in retroperitoneal infection has not been
      reported previously, which prompts us to discuss its etiology and emphasize the
      importance of physical examination.

PMID- 15479302
TI  - Use of holmium laser for removal of an intraluminal ureteric suture.
AB  - Foreign bodies placed into the ureter are uncommon. Unintentionally placed
      sutures may cause obstruction and stone formation. If not recognized, the patient
      may become symptomatic. A diagnosis of a suture in the ureter is best made and
      subsequently dealt with endoscopically. We report on laser ablation of the suture
      as a safe technique for its removal.

PMID- 15479303
TI  - Rupture of urachal diverticulum in radiation cystitis and neurogenic bladder
      dysfunction after radical hysterectomy.
AB  - We experienced a rare case of the rupture of the urachal diverticulum in
      radiation cystitis and neurogenic bladder after radical hysterectomy. A 61-year
      old woman presented with severe lower abdominal pain and urinary retention.
      Abdominal computed tomography revealed that the urachal remnant contained a large
      volume of urine that leaked to subcutaneous tissue. We excised the urachal
      diverticulum and bladder together and created a continent urinary diversion using
      transverse colon. Nine months after the operation, the patient could manage clean
      intermittent self-catheterization 6 times a day through her umbilical stoma
      without any urinary complications.

PMID- 15479304
TI  - Echinococcosis involving the liver, retrovesical and seminal vesicle presented
      with syncope.
AB  - Hydatid disease of the urogenital system, especially of the retroperitoneum and
      seminal vesicles, is a very rare condition. We report a case of hydatid disease
      located in the liver, retrovesical region and seminal vesicle that was diagnosed
      incidentally while investigating the etiology of syncope. Transabdominal and
      transrectal ultrasonography revealed hypoecoic multicystic masses which had thin
      septations and walls in the liver, retrovesical region and seminal vesicle.
      Abdominal computed tomography examination showed multicystic low attenuation
      masses in the same region. Pelvic magnetic resonance image findings revealed
      multiple cystic masses in the retrovesical region and the right seminal vesicle.
      In conclusion, the diagnosis of hydatid disease should be kept in mind with
      patients who have cystic lesions in seminal vesicle and retrovesical region.

PMID- 15479305
TI  - Implications of amyloidosis on prostatic biopsy.
AB  - Transrectal ultrasound-guided biopsy of the prostate is an integral step in the
      investigation of patients at risk of prostate adenocarcinoma. With an increasing
      number of biopsies being performed, uncommon forms of prostatic pathology will be
      identified more frequently. Amyloidosis of the prostate and/or the seminal
      vesicles may be noted on transrectal ultrasound-guided biopsy of the prostate and
      the implications of this histological diagnosis must be understood. We present
      our experience of two such cases of amyloidosis and review the literature
      regarding their management.

PMID- 15479306
TI  - Urethral condyloma acuminata following urethral instrumentation in an elderly
      man.
AB  - A 70-year-old man had undergone urethral dilatation with bougie for 8 months
      following transurethral resection of the prostate and complained papillary masses
      at the urethral meatus. Physical and endoscopic examination revealed multiple
      tumors from the urethral meatus to the bulbous urethra. These tumors were
      resected transurethrally and 5-FU cream was instilled into urethra. Microscopic
      examination revealed urethral condyloma acuminata. Human papillomavirus types
      6/11 were detected in the condylomas. As high prevalence rate of genital human
      papillomavirus was reported in penile skin of healthy men, urethral
      instrumentation including transurethral surgery might cause dissemination of
      penile skin human papillomavirus into the urethral lumen.

PMID- 15479307
TI  - Tuberculid of the penis with a scab on the nodule.
AB  - Tuberculids of the penis are extremely rare. The clinical features of tuberculids
      of the penis have been reported as ulceration or scars. We have experienced a
      case of tuberculid of the penis that appeared as a scab on nodule. A 56-year-old
      man presented with a 4-month history of a painless subcutaneous nodule at the
      glans penis. Pathological findings of the nodule showed granulomatous
      inflammation. Tuberculin tests were strongly positive, but tubercle bacilli could
      not be detected. The diagnosis was tuberculid of the penis and the patient
      received antituberculosis chemotherapy. The present paper reports an interesting
      and rare case of tuberculid of the penis with a scab on nodule.

PMID- 15479308
TI  - Extraperitoneal laparoscopic retroperitoneal lymph node dissection in supine
      position after chemotherapy for advanced testicular carcinoma.
AB  - AIM: To evaluate the feasibility and usefulness of extraperitoneal laparoscopic
      retroperitoneal lymph node dissection (RPLND) in the supine position after
      chemotherapy for advanced testicular carcinoma. METHODS: Three patients with
      advanced testicular cancer underwent chemotherapy. Although serum markers were
      decreased compared with the normal range, residual masses requiring surgical
      resection were recognized by computed tomography scanning. We applied
      extraperitoneal laparoscopic RPLND. The patients were placed in the supine
      position and the first trocar was inserted two finger widths medial to the
      anterior iliac spine. The retroperitoneal space was dilated using a preperitoneal
      distention balloon. Two more ports were inserted into the retroperitoneal space
      and surgery proceeded thereafter. RESULTS: The residual tumors were completely
      resected by laparoscopy. The procedure required 250-310 min and the bleeding
      volume was below 50 mL. Although the histopathological findings consisted only of
      necrosis in all of the patients, one patient recurred at the same place.
      CONCLUSIONS: Extraperitoneal laparoscopic RPLND in the supine position for
      residual tumors after chemotherapy is technically feasible and useful in terms of
      postoperative recovery. With regard to cancer control, further evaluation should
      be necessary.

PMID- 15479309
TI  - Long-term outcomes in survivors from critical illness.

PMID- 15479310
TI  - Effectiveness of bupropion as an aid to stopping smoking before elective surgery:
      a randomised controlled trial.
AB  - Smoking is a risk factor for complications during and after surgery, but most
      smokers are unable to quit before elective surgery. We tested the efficacy of
      bupropion in improving smoking cessation rates in this setting by enrolling 47
      patients from the elective surgery waiting list in a double-blind randomised
      controlled trial. Patients receiving bupropion had a lower daily cigarette
      consumption at the time of hospital admission, median (IQR) cigarettes per day: 6
      (2-7) vs. 15 (9-20), p = 0.046. They also had a reduction in end-expired carbon
      monoxide (p = 0.004), a known contaminant of cigarette smoke, and increased
      arterial oxygen saturation on pulse oximetry (p = 0.011). They were more likely
      to have stopped smoking at the 3-week visit (p = 0.036), but not at the 6-week
      visit (p = 0.25) or at the time of hospital admission for surgery (p > 0.99).
      This study found that smokers waiting for elective surgery are more likely to
      reduce or stop smoking when treated with bupropion.

PMID- 15479311
TI  - Manual versus target-controlled infusions of propofol.
AB  - Target-controlled infusion systems have been shown to result in the
      administration of larger doses of propofol, which may result in delayed emergence
      and recovery from anaesthesia. The aim of this study was to investigate if this
      was due to a difference in the depth of hypnosis (using the bispectral index
      monitoring) between the manual and target controlled systems of administration.
      Fifty unpremedicated patients undergoing elective surgery were randomly allocated
      to have their anaesthesia maintained with manual or target-controlled propofol
      infusion schemes. In both groups, the rate of propofol administration was
      adjusted according to standard clinical criteria while bispectral index scores
      were recorded by an observer not involved in the delivery of anaesthesia. The
      total dose of propofol used was higher in the target controlled group (mean 9.9
      [standard deviation 1.6] compared with 8.1 [1.0] mg.kg(-1).h(-1) in the manual
      group [p < 0.0001]). The times to emergence and recovery end-points were
      comparable between the two groups. The difference in the total dosage of propofol
      was mainly due to higher rate of propofol administration in the first 30 min in
      the target controlled infusion group. The bispectral index scores were lower in
      the target controlled group during this time, being significantly so over the
      first 15 min of anaesthesia. We conclude that propofol administration by a target
      controlled infusion system results in the administration of higher doses of
      propofol and lower bispectral index values mainly in the initial period of
      anaesthesia.

PMID- 15479312
TI  - A BIS-guided study of sevoflurane requirements for adequate depth of anaesthesia
      in Caesarean section.
AB  - Caesarean section carries a high risk of awareness, especially in the period
      prior to neonatal delivery. We investigated the concentration of sevoflurane
      required to maintain bispectral index (BIS) < 60 until delivery occurred. We
      enrolled 23 parturients into an up-down sequential allocation study. The median
      effective end-tidal concentration (EC(50)) of sevoflurane was defined as that
      which maintained BIS < 60 between skin incision and delivery in 50% of patients.
      This was calculated using Dixon and Massey's method. Receiver operating
      characteristic curve analysis was used to establish BIS response probability
      thresholds. The EC(50) for sevoflurane was 1.22% (1.08-1.33, 95% CI). The
      probability of maintaining BIS < 60 was < 55% at a concentration of < 1.1%; this
      increased to 80% at concentrations of 1.2-1.3%. We conclude that sevoflurane
      concentrations of at least 1.2-1.3% should be administered in uncomplicated
      Caesarean section, so as to minimise the risk of awareness and recall.

PMID- 15479313
TI  - Effect of head posture on tracheal tube position in children.
AB  - Changes in the tracheal tube tip to carina distance were measured by radiographic
      screening following various head postures in 45 children undergoing cardiac
      catheterisation under general anaesthesia who were intubated via nasal and oral
      routes. Extension of the head moved the tracheal tube away from the carina and
      flexion moved it towards the carina in both routes. Endobronchial intubation was
      noted during neck flexion in a significant proportion of children intubated
      orally but none occurred during nasal intubation. Extension produced greater
      upward movement of the tracheal tube tip in the oral route than the nasal route.
      In contrast, flexion produced greater downward movement in the nasal route in
      some patients. The direction of movement with lateral rotation and use of a
      shoulder roll was inconsistent.

PMID- 15479314
TI  - The effects of cryoanalgesia combined with thoracic epidural analgesia in
      patients undergoing thoracotomy.
AB  - This study was performed to evaluate the effects of cryoanalgesia combined with
      thoracic epidural analgesia on pain and respiratory complications in patients
      undergoing thoracotomy. Ninety patients were prospectively randomised to epidural
      analgesia alone (n = 45) or epidural analgesia and cryoanalgesia combined (n =
      45). We monitored the use of rescue pain medication and changes in forced vital
      capacity and forced expired volume in 1 s, and recorded pain and opioid-related
      side-effects during the immediate postoperative period. The incidence of post
      thoracotomy pain and numbness were also assessed up to the sixth month after
      surgery. Cryoanalgesia combined with thoracic epidural analgesia was associated
      with earlier recovery in pulmonary function, less pain during movement and a
      lower daily requirement for rescue analgesia one week after surgery. However, the
      combination of cryoanalgesia and epidural analgesia failed to decrease the
      incidence of long-term pain and numbness. In view of its associated long-term
      morbidity, cryoanalgesia combined with thoracic epidural analgesia is not
      recommended for patients undergoing thoracotomy.

PMID- 15479315
TI  - Comparison of surgical site and patient's history with a simplified risk score
      for the prediction of postoperative nausea and vomiting.
AB  - Although site of surgery and previous occurrence of postoperative nausea and
      vomiting are often used to decide whether prophylactic anti-emetic drugs are
      indicated, the value of these predictors is unclear. We compared these two risk
      factors against a simplified four-factor risk score. We analysed data from 1566
      adult inpatients who received balanced anaesthesia without prophylactic anti
      emetics. Sensitivity, specificity, predictive value and area under the receiver
      operating characteristic curve were used to quantify predictive properties.
      Nausea and vomiting occurred in 600 (38.3%) patients within 24 h. Sensitivity and
      specificity were, respectively, 47% and 59% for surgical site; 47% and 70% for
      history of postoperative nausea and vomiting; and 58% and 70% for risk score with
      three or more factors. The area under the curve for surgical site was 0.53 (95%
      CI 0.50-0.56); that for patient's history was 0.58 (95% CI 0.56-0.61) while for
      risk score it was 0.68 (95% CI 0.66-0.71; P < 0.001). Prediction using surgical
      site or patient's history alone was poor while the simplified risk score provided
      clinically useful sensitivity and specificity.

PMID- 15479316
TI  - Postoperative 12-lead ECG predicts peri-operative myocardial ischaemia associated
      with myocardial cell damage.
AB  - Peri-operative myocardial ischaemia is the single most important risk factor for
      an adverse cardiac outcome after non-cardiac surgery. The present study examines
      whether intermittent 12-lead ECG recordings can be used as an early warning tool
      to identify patients suffering from peri-operative myocardial ischaemia and
      subsequent myocardial cell damage. Fifty-five vascular surgery patients at risk
      for or with a history of coronary artery disease were monitored for peri
      operative myocardial ischaemia using intermittent 12-lead ECG recordings taken
      pre-operatively and at 15 min, 20 h, 48 h, 72 h and 84 h postoperatively. The
      effectiveness of the 12-lead ECG was gauged by examining concordance with
      continuous 3-channel Holter monitoring and capturing peri-operative myocardial
      ischaemia by serial analyses of creatine kinase myocardial band isoenzyme and
      cardiac troponin T and I. The incidence of peri-operative myocardial ischaemia
      detected by 12-lead ECG was 44% and was identifiable in most patients (88%) 15
      min after surgery. The incidence of peri-operative myocardial ischaemia detected
      by continuous monitoring was 53%, with the most severe episodes occurring intra
      operatively and during emergence from anaesthesia. The concordance of the 12-lead
      method with continuous monitoring was 72%. The concordance of creatine kinase
      myocardial band isoenzyme activity with the 12-lead method was 71% and with
      Holter monitoring 57%. The concordance of mass concentration of creatine kinase
      myocardial band with 12-lead ECG recordings was 75%, and the corresponding value
      for Holter monitoring was 68%. The concordance of cardiac troponin T and I levels
      with the 12-lead method was 85% and 87%, respectively, and concordance with
      Holter monitoring was 72% and 66%, respectively. The postoperative 12-lead ECG
      identified peri-operative myocardial ischaemia associated with subsequent
      myocardial cell damage in most patients undergoing vascular surgery.

PMID- 15479317
TI  - Prehospital airway management in Ambulance Services in the United Kingdom.
AB  - A postal survey of the 38 Ambulance Services in the United Kingdom was undertaken
      to find out what equipment is provided for paramedic crews to aid tracheal
      intubation and to confirm tracheal placement. The response rate to our survey was
      100%. Fourteen (37%) ambulance services provided neither stylet nor bougie to
      facilitate difficult intubation. The laryngeal mask airway was available to 15
      (40%) ambulance services. Seventeen (45%) ambulance services had use of a needle
      cricothyroidotomy set. Twenty-nine (76%) ambulance services had no type of device
      other than a stethoscope to confirm tracheal tube placement. This survey showed
      wide variations in the equipment for airway management available to paramedic
      crews in the United Kingdom. We recommend provision of a standard set of airway
      management equipment to all paramedic crews in the United Kingdom together with
      introduction of appropriate training programmes.

PMID- 15479318
TI  - Clearing the cervical spine in unconscious adult trauma patients: a survey of
      practice in specialist centres in the UK.
AB  - A postal questionnaire survey of neurosurgery and spinal injury departments in
      the UK was conducted to determine how they assessed the cervical spine in
      unconscious, adult trauma patients, and at what point immobilisation was
      discontinued. Of the 32 units contacted, 27 responded (response rate, 84%). Most
      centres had no protocols to guide initial imaging or when immobilisation devices
      should be removed. Most responding centres performed fewer than three plain
      radiographs, and most did not use computerised tomography routinely. Routine use
      of magnetic resonance imaging or dynamic flexion-extension fluoroscopy was rare,
      and few units regarded the latter as safe in unconscious patients. There was no
      consensus on when immobilisation of the cervical spine should be discontinued.
      Most centres that terminated immobilisation immediately after imaging did so on
      the basis of plain radiographs alone. Unconscious adult trauma patients remain at
      risk of inadequate assessment of potential cervical spine injuries.

PMID- 15479319
TI  - Effect of non-selective, non-steroidal anti-inflammatory drugs and cyclo
      oxygenase-2 selective inhibitors on the PFA-100 closure time.
AB  - The place of cyclo-oxygenase (COX)-2 selective non-steroidal anti-inflammatory
      drugs (NSAIDs) in the peri-operative period remains under discussion. Due to the
      absence of COX-2 in platelets, the risk of bleeding in patients who use selective
      NSAIDs is thought to be decreased. We studied the influence of aspirin,
      diclofenac, lornoxicam and rofecoxib on the in vitro bleeding time using the
      platelet function analyser (PFA-100). The PFA-100 simulates the process of
      platelet adhesion and aggregation after vascular injury in vitro. Measurements in
      43 volunteers were performed at three time points: before, 3 h, and 12 h after
      oral ingestion of one of the randomly assigned study medications. Aspirin,
      diclofenac and lornoxicam had a significant effect on the in vitro closure time,
      while rofecoxib did not show this effect. This supports the use of COX-2
      selective drugs in the peri-operative period to minimise the risk of bleeding.

PMID- 15479320
TI  - Effect of xenon anaesthesia on accuracy of cardiac output measurement using
      partial CO2 rebreathing.
AB  - Cardiac output (CO) determination based on partial CO(2) rebreathing has recently
      been introduced into clinical practice. The determination of flow is crucial for
      exact CO readings and the physical properties of xenon, i.e. high density and
      viscosity, may influence flow readings. This study compared echocardiography
      derived CO measurements with the partial rebreathing method during total
      intravenous (TIVA) vs. xenon-based anaesthesia. Thirty-nine patients ASA physical
      status III undergoing aortic reconstruction were randomly assigned to receive
      either xenon (Xe, n = 20) or TIVA (T, n = 19) based general anaesthetic. Paired
      measurements were taken before xenon administration, after xenon administration,
      before and after clamping of the abdominal aorta and after declamping and at
      corresponding time points in the TIVA group. Data were analysed with a Bland
      Altmann plot. Bias and precision were acceptable and comparable before xenon
      administration (T 0.54 +/- 0.92 l.min(-1) vs. Xe 0.11 +/- 1.1 l.min(-1)), but
      after xenon administration CO was largely overestimated by partial CO(2)
      rebreathing (T 0.04 +/- 0.91 l.min(-1) vs. Xe -4.0 +/- 2.1 l.min(-1)). In the
      TIVA group, bias and precision after declamping increased significantly (P <
      0.01) compared to all time points except baseline. In its current application,
      the NICO cardiac output monitor appears to be inappropriate for determination of
      CO during xenon based anaesthesia.

PMID- 15479321
TI  - Changes of serum chloride and metabolic acid-base state in critical illness.
AB  - Alterations of electrolytes and albumin cause metabolic acid-base disorders. It
      is unclear, however, to what degree these plasma components affect the overall
      metabolic acid-base state in the course of critical illness. We performed serial
      analyses of the metabolic acid-base state in 30 critically ill patients over the
      course of 1 week. We applied a physical-chemical acid-base model and used a
      linear regression model to determine the influence of sodium, chloride,
      unmeasured anions and albumin on the net metabolic acid-base state. Progressive
      hypochloraemia was identified as the main cause of developing metabolic
      alkalosis. Changes in serum chloride and unmeasured anions were responsible for
      changes of 41% and 22% in the metabolic acid-base state, respectively. Sodium and
      albumin played a minor role. In conclusion, chloride is the major determinant of
      metabolic acid-base state in critical illness.

PMID- 15479322
TI  - Ultrasound for central venous cannulation: economic evaluation of cost
      effectiveness.
AB  - We compared the economics of using two-dimensional ultrasound locating devices
      and more traditional landmark methods for central venous cannulation in the
      National Health Service (NHS). The evaluation consisted of a systematic review of
      randomised controlled trials and an economic evaluation using decision analytic
      cost-effectiveness modelling. Incremental costs per complication avoided
      associated with landmark and ultrasound central venous cannulation were modelled
      for patients scheduled for central venous cannulation. The marginal economic cost
      of using ultrasound for central venous cannulation was less than 10 pounds
      sterling per procedure, assuming that a machine is used for 15 procedures each
      week. The base case scenario implied that 2000 pounds sterling worth of resource
      savings result for every 1000 procedures undertaken and 90 avoided complications.
      Sensitivity analysis indicated that the results of modelling appear robust to the
      central assumptions used. Ultrasound guidance used in central venous cannulation
      procedures saves NHS resources even with conservative modelling assumptions.

PMID- 15479323
TI  - A prospective audit of cost of sedation, analgesia and neuromuscular blockade in
      a large British ICU.
AB  - Bottom-up costs of sedative, analgesic and neuromuscular blocking drugs used in
      the intensive care unit have not been reported. We performed a prospective audit
      of the cost of these drugs using a bottom-up approach by prospectively recording
      the daily amount of drugs administered to patients over a 3-month period. Of 172
      admissions, complete data were collected for 155 (92%). Propofol and alfentanil
      were the drugs most commonly used, being administered to 136 (88%) and 106 (68%)
      patients, respectively. The total cost was 14,070 pounds sterling, which was 81%
      of the pharmacy figure (based on central purchasing). Ninety-four per cent of the
      cost was for drugs administered to the 50% of patients who stayed in the
      intensive care unit longer than 48 h. The median (interquartile range [range])
      cost per day was 9.30 pounds sterling (3.60-20.10 [0-61.20]). This represents
      less than 1% of reported total daily cost of intensive care per patient.

PMID- 15479324
TI  - Continuous assessment of right ventricular ejection fraction: new pulmonary
      artery catheter versus transoesophageal echocardiography.
AB  - In 25 cardiac surgical patients, right ventricular ejection fraction was
      continuously measured with a new pulmonary artery catheter and transoesophageal
      echocardiography, scanning the 'fractional area change' in a standardised
      transatrial cross section area. Measurements were recorded at three predefined
      time points (pre-, intra-, and postoperatively). Both methods were compared using
      the Bland-Altman analysis. Comparing right ventricular ejection fraction values
      obtained from the pulmonary artery catheter with those assessed by
      transoesophageal echocardiography, bias was -3.7%, with a precision of 30.9%.
      Bias and precision significantly improved when the heart rate was less than 100
      beats.min(-1), pulmonary artery pressures were low and cardiac performance
      adequate. In conclusion, the new continuous pulmonary artery catheter system
      appears to be a valid and useful bedside monitoring device in the haemodynamic
      management of critically ill patients.

PMID- 15479325
TI  - Accurate continuous drug delivery at low infusion rate with a novel
      microvolumetric infusion pump (MVIP): pump design, evaluation and comparison to
      the current standard.
AB  - Infusion devices for continuous and precise drug administration are indispensable
      tools in anaesthesia and critical care medicine. Problems such as start-up
      delays, non-continuous flow and susceptibility to hydrostatic pressure changes at
      low infusion rates resulting in accidental bolus release or prolonged flow
      interruption are inherent to current infusion technology. In order to improve
      precise drug delivery, an innovative technical concept has been realised in a
      novel microvolumetric infusion pump (MVIP) device. The MVIP principle includes
      repeated filling and emptying of a non-compliant microsyringe without the use of
      valves. The performance of the MVIP prototype has been evaluated and compared
      with standard syringe infusion pump assemblies. The novel MVIP concept has
      thereby proven to eliminate most problems during infusion start-up, steady state
      flow and vertical pump displacement, and has the potential of revolutionising
      infusion technology and setting a new dimension in patient safety.

PMID- 15479326
TI  - Teaching cannula cricothyroidotomy.

PMID- 15479327
TI  - Oral dantrolene.

PMID- 15479328
TI  - Intubation via single-use laryngeal mask airways.

PMID- 15479329
TI  - Pulmonary aspiration through a Cobra PLA.

PMID- 15479330
TI  - Hazards of submental tracheal intubation.

PMID- 15479331
TI  - An unusual postoperative burn.

PMID- 15479332
TI  - The need to move the take-off point of the pilot tube.

PMID- 15479333
TI  - Manufacturers' response to criticism.

PMID- 15479334
TI  - Consent for publication of a case report.

PMID- 15479335
TI  - Strength of disposable laryngoscopes.

PMID- 15479336
TI  - Inhibition of hiccups by the laryngeal mask airway is ineffective.

PMID- 15479337
TI  - A reusable ultrasound phantom.

PMID- 15479338
TI  - European computer driving licence.

PMID- 15479339
TI  - Detection of impending abdominal compartment syndrome.

PMID- 15479340
TI  - Chloroform, vitamin B12, and the tragic lives of Robert M. Glover and Horace
      Wells.

PMID- 15479341
TI  - Large ovarian cyst as a cause of aortocaval compression.

PMID- 15479342
TI  - A response to 'Cerebral and extracerebral release of protein S100B in cardiac
      surgical patients', Snyder-Ramos SA, Gruhlke T, Bauer H, Bauer M, Luntz AP,
      Motsch J, Martin E, Vahl CF, Missler U, Wiesmann M and Bottiger BW, Anaesthesia
      2004; 59: 344-9.

PMID- 15479343
TI  - A response to 'Decreasing epidural failure', Picton P and Das S, Anaesthesia
      2004; 59: 729.

PMID- 15479345
TI  - A response to 'Abdominal muscle action during expiration can impair pressure
      controlled ventilation', Prasad CV and Drummond GB, Anaesthesia 2004; 59: 715-8.

PMID- 15479346
TI  - A response to 'Difficult Airway Society guidelines for management of the
      unanticipated difficult intubation', Henderson JJ, Popat MT, Latto IP and Pearce
      AC, Anaesthesia 2004; 59: 675-94.

PMID- 15479349
TI  - A response to 'Effect of chronic B-blockade on peri-operative outcome in patients
      undergoing non-cardiac surgery: an analysis of observational and case control
      studies', Giles JW, Sear JW and Foex P, Anaesthesia 2004; 59: 574-83.

PMID- 15479350
TI  - A response to 'The effect of critical care outreach on postoperative serious
      adverse events', Story DA, Shelton AC, Poustie SJ, Colin-Thome NJ and McNicol PL,
      Anaesthesia 2004; 59: 762-6.

PMID- 15479351
TI  - A response to 'Difficult Airway Society guidelines for management of the
      unanticipated difficult intubation', Henderson JJ, Popat MT, Latto IP and Pearce
      AC, Anaesthesia 2004; 59: 675-94.

PMID- 15479353
TI  - Review article: pegylated interferons: chemical and clinical differences.
AB  - Pegylated interferon therapy for the treatment of chronic hepatitis C virus
      provides significant increases in sustained virological response rates compared
      with standard interferons. Two pegylated interferons are now available and are
      used in conjunction with ribavirin to maximize response rates in infected
      patients. The two pegylated interferons, peginterferonalpha-2a and
      peginterferonalpha-2b, differ substantially in terms of their chemical and
      structural characteristics, pharmacokinetic and pharmacodynamic properties, and
      dosing and administration. A full understanding of the differences between the
      two drugs is important to maximize the clinical benefits. Controlled studies
      designed to characterize the effects of the two drugs on viral kinetics and
      sustained virological response rates are emerging and may help to shed additional
      light on the use of these compounds in patients with chronic hepatitis C.

PMID- 15479354
TI  - Review article: therapeutic roles of acupuncture in functional gastrointestinal
      disorders.
AB  - Acupuncture has been practiced empirically in China for several millennia, and is
      being increasingly accepted by practitioners and patients worldwide. Functional
      gastrointestinal disorders are common in clinical gastroenterology. The
      prevalence of one or more functional gastrointestinal disorders is estimated to
      be as high as 70% in general population using Rome diagnostic criteria. Since
      functional gastrointestinal disorders are diagnosed based on symptoms and the
      exact aetiologies for most of functional gastrointestinal disorders are not
      completely known, it is not unusual that the treatment for these disorders is
      unsatisfactory and alternative therapies are attractive to both patients and
      practitioners. During the latest decades, a considerable number of studies have
      been performed on acupuncture for the treatment of functional gastrointestinal
      disorders and underlying mechanisms. In this article, we reviewed available data
      in the literature on the applications and mechanisms of acupuncture for the
      treatment of functional gastrointestinal disorders, including functional
      oesophageal disorders, nausea and vomiting, functional dyspepsia, irritable bowel
      syndrome, constipation, etc. A summary is provided based on the quality and
      quantity of published studies regarding the efficacy of acupuncture in treating
      these various disorders. In addition, the methodology of acupuncture is also
      introduced.

PMID- 15479355
TI  - Increased incidence of azathioprine-induced pancreatitis in Crohn's disease
      compared with other diseases.
AB  - BACKGROUND: Azathioprine is widely used in Crohn's disease. A major drawback is
      the occurrence of side-effects, especially acute pancreatitis. Acute pancreatitis
      is rarely seen when azathioprine is used for other diseases than Crohn's disease.
      AIM: To survey side-effects of azathioprine after liver or renal transplantation,
      for systemic lupus erythematosis, Wegener's granulomatosis, autoimmune hepatitis,
      rheumatoid arthritis, ulcerative colitis or Crohn's disease. METHODS: A
      computerized search using the term 'azathioprine' or 'imuran' was performed on
      the Hospital Information System of the university hospital Groningen, resulting
      in 1564 patients matching our criteria. RESULTS: Eleven of 224 patients with
      Crohn's disease experienced acute pancreatitis (4.9%) compared with two of 129
      (1.5%) with autoimmune hepatitis, two of 388 (0.5%) after renal transplantation,
      one of 254 (0.4%) after liver transplantation. Acute pancreatitis was more
      prevalent in Crohn's disease compared with any other disease. Azathioprine
      toxicity necessitating withdrawal occurred significantly (P < 0,05) more in
      rheumatoid arthritis (78 of 317), ulcerative colitis (20 of 94) and Crohn's
      disease (52 of 224) compared with systemic lupus erythematosis (five of 73),
      Wegener's granulomatosis (six of 85), autoimmune hepatitis (eight of 129), after
      liver transplantation (17 of 254) and after renal transplantation (22 of 388).
      CONCLUSIONS: Acute pancreatitis is strongly associated with Crohn's disease and
      rarely occurs with other underlying conditions. Overall azathioprine-induced
      toxicity and the necessity of withdrawal is more common in inflammatory bowel
      disease and rheumatoid arthritis compared with other diseases.

PMID- 15479356
TI  - Effect of antitumour necrosis factor-alpha therapy on bone turnover in patients
      with active Crohn's disease: a prospective study.
AB  - BACKGROUND AND AIMS: Patients with Crohn's disease are at increased risk of
      osteoporosis. Disease activity and circulating proinflammatory cytokines are
      thought to play a role in this process. Infliximab, a chimaeric antitumour
      necrosis factor-alpha antibody is effective in the treatment of Crohn's disease.
      The aim of this study was to investigate the impact of treatment with infliximab
      on bone turnover in Crohn's disease patients. METHODS: This was a prospective
      trial. Twenty-four patients with active Crohn's disease were treated with
      infliximab (5 mg/kg). Bone markers were assayed pre- and post-treatment. Bone
      formation was measured using serum bone-specific alkaline phosphatase and total
      osteocalcin and bone resorption using serum N-telopeptide cross-linked type 1
      collagen. RESULTS: Infliximab therapy caused a significant increase in both
      markers of bone formation in patients with active Crohn's disease. No significant
      change in the bone resorption marker serum N-telopeptide cross-linked type 1 was
      found. CONCLUSION: Infliximab therapy had a significant beneficial effect on bone
      metabolism in patients with active Crohn's disease. These findings further
      support the theory that active ongoing inflammation and high levels of
      circulating cytokines play a pivotal role in the pathogenesis of bone loss in
      patients with Crohn's disease.

PMID- 15479357
TI  - Nicotine enemas for treatment of ulcerative colitis: a study of the
      pharmacokinetics and adverse events associated with three doses of nicotine.
AB  - BACKGROUND: Transdermal nicotine is of value in active ulcerative colitis but
      causes adverse events because of systemic absorption. Nicotine enemas may give
      rise to fewer adverse events. AIM: To assess the pharmacokinetics of nicotine
      enemas in three doses. METHODS: Thirteen volunteers, all non-smokers but three ex
      smokers, were given enemas on separate occasions containing 3, 6 and 9 mg of
      nicotine, in ascending dose order. Adverse events were recorded and blood samples
      taken over 8 h for measurement of serum nicotine and cotinine. RESULTS: Enemas
      were retained by most subjects. Eleven of 14 adverse events were 'early'--30-105
      min after the enema, corresponding to maximum plasma nicotine concentrations;
      three events were later, 4-8 h after the enema and unrelated to the tmax. 'Early'
      adverse events occurred in eight subjects--six with 9 mg. The three highest
      plasma nicotine concentrations were with 9 mg and associated with headache,
      nausea and sweating. Only one had adverse events with 3 mg and withdrew from the
      study. Nicotine Cmax with 6 and 9 mg doses were respectively two and three times
      the value with 3 mg. Peak nicotine concentrations occurred 44-50 min after the
      enema. CONCLUSION: The 6 mg dose of nicotine probably represents the dose to use
      in clinical practice - for the highest therapeutic dose with a low risk of
      adverse events.

PMID- 15479358
TI  - Treatment of Budd-Chiari syndrome in a liver transplant unit, the role of
      transjugular intrahepatic porto-systemic shunt and liver transplantation.
AB  - BACKGROUND: Budd-Chiari syndrome is an uncommon cause of liver failure usually
      associated with an underlying hypercoagulable state. AIM: To evaluate current
      trends in management of Budd-Chiari syndrome at our institution. METHODS: Twenty
      two patients with Budd-Chiari syndrome underwent transjugular intrahepatic porto
      systemic shunt, liver transplantation, or both in between 1992 and 2001. We
      analysed underlying diagnosis, medical therapy, complications, follow-up and
      overall outcomes. RESULTS: Five patients (17%) presented with fulminant liver
      failure and 17 patients (83%) with new-onset ascites or chronic liver disease.
      Seventeen patients (74%) underwent transjugular intrahepatic porto-systemic
      shunt: improvement or stabilization occurred initially in 14 (82%), whereas the
      other three patients died within a month. At a mean 3 years follow-up eight
      patients (47%) continued to do well clinically and four have died (23.5%); seven
      have required transjugular intrahepatic porto-systemic shunt revisions (mean 2.3
      interventions), five have experienced transjugular intrahepatic porto-systemic
      shunt occlusion managed with new transjugular intrahepatic porto-systemic shunt
      placement and five patients underwent subsequent transplantation. Of the 10
      patients who underwent liver transplantation, patient and graft survival are 80%
      at a mean 5.7 years of follow-up. No patient developed post-transplant Budd
      Chiari syndrome. CONCLUSIONS: Transjugular intrahepatic porto-systemic shunt is
      usually feasible in patients with Budd-Chiari syndrome, and is best suited as a
      bridge to more timely liver transplantation. Long-term success of transjugular
      intrahepatic porto-systemic shunt is limited and usually requires revision,
      placement of a new shunt or liver transplantation. Liver transplantation with
      chronic anticoagulation offers excellent short- and medium-term patient and graft
      survival. In our series, there was no recurrence of Budd-Chiari syndrome after
      liver transplantation.

PMID- 15479359
TI  - Dwell time and functional failure in percutaneous endoscopic gastrostomy tubes: a
      prospective randomized-controlled comparison between silicon polymer and
      polyurethane percutaneous endoscopic gastrostomy tubes.
AB  - BACKGROUND: Silicone percutaneous endoscopic gastros-tomy (PEG) tubes are
      associated with more short-term complications and possibly fail sooner than those
      made of polyurethane. Understanding the deterioration and long-term complications
      leading to tube failure has important clinical and cost implications. AIM: To
      compare dwell time and patterns of failure ofsilicone polymer and polyurethane
      PEG tubes. METHODS: Participants randomized to receive a siliconepolymer (n = 76)
      or polyurethane (n = 62) PEG werevisited monthly for 540 days, until death or
      tube removal. Tube and exit site characteristics and reasons for removal were
      recorded. RESULTS: Tube failure occurred in 25% of silicone PEGs and 12.9% of
      polyurethane PEGs. Mean tube survival for silicone PEGs was 377.2 days (CI: 326
      428) and for polyurethane 436.8 days (CI: 383-490; P = 0.13). A greater
      proportion of silicone PEGs developed intralumenal colonization and altered tube
      integrity than polyurethane (P < 0.001). Silicone PEGs blocked more frequently (P
      < 0.005) and were removed because of irreversible blockage more often than
      polyurethane PEGs (P < 0.05). Silicone PEGs with reversible blockage and tube
      integrity changes had a significantly greater probability of failure than
      silicone tubes without these changes (P < 0.005 and P < 0.05, respectively).
      CONCLUSIONS: Observations over time indicate that sili-cone PEGs are more
      susceptible than polyurethane PEGs to tube deterioration, resulting in
      substantially increased management demands to sustain patients' feeding and
      medication schedules.

PMID- 15479360
TI  - Intravenous and oral lansoprazole are equivalent in suppressing stimulated acid
      output in patient volunteers with erosive oesophagitis.
AB  - BACKGROUND: Some patients requiring acid suppression may be unable to take oral
      medications. AIM: To compare the gastric acid inhibition effects of lansoprazole
      30 mg administered either intravenous or orally in erosive oesophagitis patients.
      METHODS: The study included 87 Helicobacter pylori-negative patients with erosive
      oesophagitis. Each patient received 7 days of lansoprazole 30 mg orally prior to
      being randomized in a 3:1 fashion to intravenously lansoprazole 30 mg or
      intravenously placebo for 7 days. Basal acid output and pentagastrin-stimulated
      acid output were measured on days 8, 9 and 15. RESULTS: Median pentagastrin
      stimulated acid output was 7.2 mmol/h after 7 days of oral lansoprazole. The
      median pentagastrin-stimulated acid output increased to 7.6 mmol/h after 7 days
      of intravenous lansoprazole compared with 26.9 mmol/h after intravenous placebo
      (P < 0.001). CONCLUSIONS: Lansoprazole 30 mg administered intravenous was
      equivalent to the 30 mg oral capsule in gastric acid suppression. Intravenous
      proton pump inhibitor therapy represents an important treatment option for those
      with acid-related diseases who are unable to take oral medications.

PMID- 15479361
TI  - International validation of ReQuest in patients with endoscopy-negative gastro
      oesophageal reflux disease.
AB  - BACKGROUND: Reflux Questionnaire (ReQuest), a newly developed gastro-oesophageal
      reflux disease-sensitive scale, can be used to reliably evaluate the effect of
      treatment on gastro-oesophageal reflux disease symptoms. AIM: International
      validation of this scale, in patients suffering from endoscopy-negative gastro
      oesophageal reflux disease. METHODS: In this open, multicentre and multinational
      clinical trial 840 endoscopy-negative gastro-oesophageal reflux disease patients
      received pantoprazole 20 mg daily for 28 days. The long and short versions of
      ReQuest were completed both in the pre-treatment and treatment phases. For scale
      development an item reduction analysis was performed. Internal consistency, test
      retest reliability and responsiveness were calculated for psychometric analysis.
      Construct validity was evaluated by comparison with the Gastrointestinal Symptom
      Rating Scale and the Psychological General Well-being questionnaire by means of
      correlation coefficients. RESULTS: Factor analyses confirmed the content validity
      of both long and short version of ReQuest. Psychometric calculations proved high
      internal consistency (Cronbach's alpha: 0.9), test-retest reliability [Intraclass
      Correlation Coefficient: 0.9 (long vs. long) and 0.8 (short vs. short)], and
      responsiveness (Responsiveness Index 320.3) of the scale, for which also good
      construct validity was achieved (correlation coefficient: Gastrointestinal
      Symptom Rating Scale -0.6; Psychological General Well-being -0.4). CONCLUSION:
      ReQuest proved valid, reliable, and responsive in this multinational clinical
      trial to evaluate treatment response in endoscopy-negative gastro-oesophageal
      reflux disease patients.

PMID- 15479362
TI  - Effect of low-dose rabeprazole and omeprazole on gastric acidity: results of a
      double blind, randomized, placebo-controlled, three-way crossover study in
      healthy subjects.
AB  - BACKGROUND: The treatment of acid-related symptoms requires rapid and consistent
      acid suppression, especially with on-demand regimens. AIM: To compare the
      antisecretory activity of low-dose rabeprazole and omeprazole in healthy,
      Helicobacter pylori-negative subjects. METHODS: In this randomized, double-blind,
      placebo-controlled, three-way crossover study, 27 volunteers were given
      rabeprazole 10 mg, omeprazole 10 mg, or placebo once daily for 7 days with a 10
      14-day washout between treatments. Intragastric pH was monitored for 24-h on days
      1 and 7 of each treatment. RESULTS: Median gastric pH was significantly higher
      with rabeprazole than with omeprazole or placebo: day 1: 2.3, 1.4 and 1.3,
      respectively (P = 0.0056, rabeprazole vs. omeprazole; P < 0.0001, rabeprazole vs.
      placebo); day 7: 3.7, 2.2 and 1.3, respectively (P = 0.0016 rabeprazole vs.
      omeprazole; P < 0.0001, rabeprazole vs. placebo). Time with gastric pH above 4
      was significantly higher with rabeprazole than with omeprazole: day 1, 5.8 h vs.
      3.7 h, respectively (P < 0.02); day 7, 10.5 h vs. 4.6 h, respectively (P =
      0.0008). CONCLUSIONS: Rabeprazole 10 mg provides more rapid acid inhibition
      compared with omeprazole 10 mg. After 7 days, the time with pH above 4 is more
      than doubled with rabeprazole 10 mg vs. omeprazole 10 mg.

PMID- 15479363
TI  - Non-cardiac chest pain: predictors of health care seeking, the types of health
      care professional consulted, work absenteeism and interruption of daily
      activities.
AB  - AIMS: To determine the predictors of health care seeking, assess the types of
      health care professional consulted and to calculate the work absenteeism rates
      and interruptions to daily activities among non-cardiac chest pain patients.
      METHODS: A total of 212 patients who presented to a Tertiary Hospital Emergency
      Department over a 1-year period with acute chest pain were assessed according to
      a standard diagnostic protocol and completed the Chest Pain Questionnaire (CPQ).
      RESULTS: In the previous 12 months prior to presentation to the Emergency
      Department, 78% of patients had seen a health care professional for chest pain.
      The main health care professionals seen were general practitioners (85%),
      cardiologists (74%) and gastroenterologists (30%). Work absenteeism rates because
      of non-cardiac chest pain were high (29%) as were interruptions to daily
      activities (63%). Multiple logistic regression found that acid regurgitation was
      the only independent predictive symptom associated with consulting for non
      cardiac chest pain (OR = 3.97, 95% CI: 1.25-12.63). CONCLUSIONS: Consulting for
      chest pain is common is this group of patients. The type of health care
      professional seen appears to be moderated by the frequency and severity of reflux
      symptoms among these chest pain patients. Work absenteeism and interruptions to
      daily activities is high among chest pain sufferers.

PMID- 15479364
TI  - WFH: back to the future.
AB  - This paper outlines the history of the World Federation of Hemophilia (WFH) and
      its work. The WFH produces a number of publications each year, and conducts
      regular surveys and data collection. Two of its most important roles are in the
      provisions of programmes to developing countries, and in promoting the views of
      the haemophilia community on issues that impact on the lives of people with
      haemophilia. Further initiatives are planned in the future to increase the length
      and quality of life for those living with haemophilia.

PMID- 15479365
TI  - Comprehensive care for haemophilia around the world.
AB  - Comprehensive haemophilia care has been defined as the continuing supervision of
      all medical and psychosocial factors affecting the person with haemophilia
      family. Services offered by haemophilia treatment centres (HTCs) adopting the
      comprehensive care model include establishing prophylaxis and other treatment
      protocols, development of psychosocial, education and research programme,
      maintenance of a patient registry, genetic and reference diagnostic services and
      orchestration and management of a wide variety of multidisciplinary
      interventions. Most centres practising this model of care are based in developed
      countries and can meet costs for plentiful treatment products through government
      or insurance-company funding. Not all the programmes are dependent on the level
      of product supply, however, and many have been supported in countries with
      emerging economies as part of national healthcare systems, particularly in
      relation to blood management. In this paper we present perspectives from
      different areas of the world on how to adopt, adapt and achieve economically
      appropriate models of comprehensive care.

PMID- 15479366
TI  - Haemophilia in the developing world: successes, frustrations and opportunities.
AB  - There is a need to bridge key gaps between high- and low-income countries and
      individuals; between health policy and clinical practice; and between producers
      and users of healthcare technology and scientific evidence. The objective of this
      report was to perform a diagnosis of the situation in the developing world
      through a survey. This survey was conducted to gather specific information on
      various aspects related to haemophilia. Countries were chosen by their
      comparability in infant and adult mortality rates according to the
      regionalization proposed by the World Health Organization. These indicators are
      very sensitive to socioeconomic conditions, and have been widely used to study
      health inequalities. All regions, except Africa and the East Mediterranean, were
      represented. Africa was excluded because its indicators were not comparable. The
      East Mediterranean was not represented because of difficulties in contacting
      investigators. Twenty-one country representatives were contacted, and 11 answered
      the questionnaire. Successes obtained by developing countries are based more on
      the skills and creativity of the local professionals than on the availability of
      state-of-the-art technology. Frustrations were related to disease
      underregistration and the limited availability of treatment products. Haemophilia
      care in the developing world is not as fair as we would like it to be.
      Governments do not always cover treatment costs, and a very small percentage of
      the national health budgets is allotted to haemophilia care. The role of the
      World Federation of Hemophilia was considered crucial by all the investigators
      surveyed. Training programmes and supply of factor concentrates were the main
      contributions identified by the respondents.

PMID- 15479367
TI  - Evidence-based treatment of haemophilia.
AB  - Haemophilia care is effective but therapy is expensive. Despite concentrates
      being available in some areas for more than 30 years, many scientific questions
      concerning the management of haemophilia, such as what doses and duration of
      factor are required for different bleeding episodes or for surgical procedures,
      remain inadequately answered. Modern rigorous methods of assessment of the
      evidence both assist in determining what facts are available, how reliable the
      evidence is, and also help to define what studies need to be done. Cochrane
      methodology can be applied to haemophilia, and an assessment of prophylaxis
      provides an example. International collaborative studies would be valuable and
      require enthusiastic participants.

PMID- 15479368
TI  - Models for psychosocial services in the developed and developing world.
AB  - This paper is based on the assumption that psychosocial services can add
      important mental and social dimensions to the traditional concepts of help and
      medicine. Peer support which has been established world-wide for people with
      haemophilia and their families is invaluable and irreplaceable. However the role
      of the professional psychosocial worker is underutilized in most countries,
      mostly because of lack of financial resources. This paper will argue that skilled
      workers can assist individuals and groups to reach their full potential in a
      variety of creative and non-threatening ways. Psychosocial workers have strict
      codes of conduct and requirements relating to accreditation to ensure
      accountability in their work. They can work in a variety of individual roles and
      have a wide range of individual mandates within work settings.

PMID- 15479369
TI  - Disease-specific quality-of-life measurement tools for haemophilia patients.
AB  - The purpose of this paper is to summarize the state of the art in measuring
      quality of life in haemophila populations. The paper reviews the measures
      recently included in haemophila trials in the published literature. It also
      summarizes the development of four new disease-specific measures of health
      related quality of life. Two of these were developed for children (the Haemo-QoL
      and the CHO-KLAT), and two for adults (the Hemofilia-QoL and the Hemolatin-QoL).
      These new measures show promise for use in clinical trials. Further research is
      in progress to complete the psychometric testing and cross-cultural validation.

PMID- 15479370
TI  - Minimizing factor requirements for surgery without increased risk.
AB  - The most common type of surgical procedure in patients with haemophilia is
      orthopaedic surgery on the lower limb. These procedures are of great importance
      for the improvement of the function and quality of life of patients with
      haemophilia, but in many countries resources are lacking to provide the factor
      concentrates needed for these operations. We have attempted to reduce the level
      of replacement during and after total hip or total knee replacement without
      jeopardizing the outcome of the procedures. The results from 30 operations in 27
      patients are presented. Steady-state levels down to 0.5 IU mL(-1) did not appear
      to increase the amount of blood loss or cause an increased incidence of
      complications, compared with higher levels. In addition, we review the
      possibilities to reduce the amount of factor concentrate by performing a
      combination of orthopaedic procedures and using local haemostatic agents or
      antifibrinolytic agents.

PMID- 15479371
TI  - The impact of information technology on haemophilia care.
AB  - The past decade has seen an explosion in the use of computers, data programs,
      hand-held electronic devices and the Internet. How these advances impact on
      haemophilia management both now and in the future are discussed from the
      perspective of haemophilia registries, Internet-based electronic haemophilia
      treatment records, and the potential for haemophilia telehealth.

PMID- 15479372
TI  - Emerging and receding risks of therapeutic regimens for haemophilia.
AB  - During the past two decades, the improvement of therapeutic agents for the
      management of haemophilia has created the opportunity for individuals with
      haemophilia to live normal lives. However, in some instances, the progress made
      has been accompanied by emergence of unexpected risks and other new
      complications. A number of viruses have either emerged, or become greater risks
      to people with haemophilia. In addition, the drive of many countries towards self
      sufficiency in blood products may in fact be endangering people with haemophilia
      by restricting blood donation to a pool of donors with high infection risk,
      discouraging commercial interests from developing safer products, and
      discouraging use of 'foreign' products even where that may be the safer option.
      Gene therapy for haemophilia, although an encouraging new treatment, has brought
      with it a number of adverse events, including risk of virus infection and
      development of carcinomas. The risk of inhibitors is still the most important
      problem for people with haemophilia, and a recent report showed that the type of
      factor concentrate does not impact significantly on this risk. Despite the advent
      of new and promising treatments for haemophilia, heathcare providers must be
      alert to new risks posed by them.

PMID- 15479373
TI  - New high-technology products for the treatment of haemophilia.
AB  - This review will focus on new technologies in development that promise to lead to
      further advances in haemophilia therapeutics. There has been continued interest
      in the bioengineering of recombinant factor VIII (rFVIII) and factor IX (rFIX)
      with improved function to overcome some of the limitations in current treatment,
      the high costs of therapy and to increase availability to a broader world
      haemophilia population. Bioengineered forms of rFVIII, rFIX or alternative
      haemostatic molecules may ultimately have an impact on improving the efficacy of
      therapeutic strategies for the haemophilias by improving biosynthesis and
      secretion, functional activity, half-life and immunogenicity. Preventing and
      suppressing inhibitors to factor (F) VIII remain a challenge for both clinicians
      and scientists. Recent experiments have shown that it is possible to obtain anti
      idiotypic antibodies with a number of desirable properties: (i) strong binding
      avidity to FVIII inhibitors; (ii) neutralization of inhibitory activity both in
      vitro and in vivo; (iii) cross-reactivity with antibodies from unrelated
      patients, and (iv) no interference with FVIII function. An alternative, although
      complementary approach, makes use of peptides derived from filamentous-phage
      random libraries. Mimotopes of FVIII can be obtained, which bind to the paratope
      of inhibitory activity and neutralize their activity both in vitro and in vivo.
      In this paper, we review advanced genetic strategies for haemophilia therapy.
      Until recently the traditional concept for gene transfer of inherited and
      acquired haematological diseases has been focused on how best to obtain stable
      insertion of a cDNA into a target-cell genome, allowing expression of a
      therapeutic protein. However, as gene-transfer vector systems continue to
      improve, the requirement for regulated gene transcription and hence regulated
      protein expression will become more critical. Inappropriate protein expression
      levels or expression of transferred cDNAs in non-intended cell types or tissues
      may lead to target-cell toxicity or activation of unwanted host immune responses.
      Regulated protein expression requires that the transferred gene be transferred
      with its own regulatory cassette that allows for gene transcription and
      translation approaching that of the normal gene in its endogenous context. New
      molecular techniques, in particular the use of RNA molecules, now allow for
      transcription of corrective genes that mimic the normal state.

PMID- 15479374
TI  - Variant Creutzfeldt-Jakob disease: risk of transmission by blood and blood
      products.
AB  - Variant Creutzfeldt-Jakob disease (CJD) is a novel acquired human prion disease
      apparently resulting from exposure to the bovine spongiform encephalopathy (BSE)
      agent. Variant CJD differs from other human prion diseases in that the disease
      associated form of the prion protein and infectivity are readily detectable in
      lymphoid tissues throughout the body. Lymphoid tissues and lymphocytes are
      implicated in the peripheral pathogenesis of prion diseases (where infectivity
      may be detected during the preclinical phase of the illness), giving rise to
      concerns that blood and blood products may also contain infectious particles,
      representing a possible source of iatrogenic spread of variant CJD. This concern
      has been reinforced following the experimental transmission of BSE in a sheep
      model by transfusion of blood and buffy coat from animals in the preclinical
      phase of the illness, and the recent identification of a UK case of variant CJD
      in a patient who had received packed red blood cells that had been donated by an
      individual who subsequently died from variant CJD. Studies in animal models
      suggest that most prion infectivity in blood may be cell-associated, with lower
      levels in the plasma, and there is evidence to suggest that any infectivity
      present may be reduced during the process of plasma fractionation. However, the
      possibility that plasma or blood products could transmit the disease cannot be
      excluded. Further studies are required to develop more sensitive means to detect
      disease-associated prion protein in blood; such techniques could be employed for
      screening purposes to reduce exposure to contaminated products and to assist with
      risk management in potentially exposed individuals.

PMID- 15479376
TI  - Product delivery in the developing world: options, opportunities and threats.
AB  - While many developed countries are moving to recombinant coagulation factors as
      their preferred modality for delivering haemophilia care, the cost of these
      products currently impedes their access by developing countries. A number of
      options are available to these countries for the provision of plasma-derived
      therapeutic products. The decreasing market for plasma-derived coagulation
      factors in the developed world is leading to the generation of a surplus of these
      products and an ability to offer them outside their traditional markets if prices
      are affordable. Current indications are that the commercial fractionation
      industry of the developed world has an excess capacity in both available plasma
      and fractionation plants. It would seem that accessing this capacity might have
      attractions for the developing world. Countries wedded to achieving self
      sufficiency in haemophilia products may elect to develop a strategy for
      fractionating domestically sourced plasma. This may be achieved by the generation
      of a capacity to fractionate within the country or by contracting the
      fractionation to an external agency overseas. However, reliance on domestic
      plasma should not be allowed to impede access to sufficient and safe coagulation
      products. Irrespective of the route chosen, products need to attain satisfactory
      compliance to standards for safety, quality and efficacy. This is best done
      through alignment of the products with the requirements of credible regulatory
      agencies. While the approval of the mainstream regulators of the developed world
      affords considerable assurance regarding product quality, the increasing efforts
      made by fractionation agencies in the developing world to attain best practice is
      commendable and augurs well for the enhancement of haemophilia care in these
      countries.

PMID- 15479375
TI  - Haemophilic factors produced by transgenic livestock: abundance that can enable
      alternative therapies worldwide.
AB  - Haemophilia replacement factors, both plasma-derived and recombinant, are in
      relatively short supply and are high-cost products. This has stymied the study
      and development of alternative methods of administration of haemophilia therapy
      even in the most economically advanced countries, owing to the large amounts of
      material needed because bioabsorption and bioavailability of haemophilic factors
      can be less than 10% when using non-intravenous routes of delivery. There is
      therefore a need to increase access to therapy worldwide by decreasing the cost
      and increasing the abundance so that therapy can be achieved through simplified,
      alternative delivery methods. Transgenic livestock have been used to produce
      haemophilic factors in milk. Only the pig mammary gland has been shown to carry
      out the post-translational processing necessary to enable both the biological
      activity and long circulation half-life needed for therapeutic glycoproteins.
      Furthermore, the large amounts of recombinant protein that can be produced from
      pig milk make feasible the use of alternative delivery methods such as oral,
      intratracheal, subcutaneous, and intramuscular administration.

PMID- 15479377
TI  - Regulatory challenges to global harmonization and expanded access to
      concentrates: how will regulators balance the increasing cost of new safety
      requirements with the desire to increase the availability of affordable product?
AB  - The provision of concentrates of the deficient coagulation factors is an
      essential component of the provision of comprehensive haemophilia care. Their
      safety, quality and efficacy need to be assured independently of the measures
      dictated by the market and the individual manufacturers. Over the past 20 years,
      this assurance has become the role of regulatory authorities, which in the
      developed world have generated a framework that assesses haemophilia products as
      medicines in the highest category of risk relative to other therapeutic agents.
      Systems of official regulation mandating standards and other measures are now
      coupled with voluntary standards adopted by industry bodies as additional
      features of a comprehensive nexus of arrangements contributing to product quality
      and risk minimization. Currently, the regulation of products for haemophilia in
      less developed economies relies on reference to decisions in the first-world
      authorities. This may not always result in optimal outcomes as most of the
      haemophilia care in the developing world is through local plasma and
      cryoprecipitate, which are not subject to the oversight of mainstream regulators.
      Furthermore, the emergence of companies based outside the developed world and
      seeking to supply the emerging economies of the developing world with haemophilia
      concentrates has necessitated new strategies for regulation that are independent
      of the established frameworks. Overall, the principles used by mainstream
      agencies may be applied in all environments seeking to assure the quality of
      haemophilia care. Applied properly, they can contribute to maintaining the
      delivery of a form of therapy that is nowadays amongst the safest in therapeutic
      practice. A rigid interpretation can seriously impede access to treatment, and
      therefore the development of independent expertise and appropriate strategies in
      assuring product safety and quality in the developing world is essential if
      patient safety and access to products can be assured.

PMID- 15479378
TI  - Physical therapy and imaging outcome measures in a haemophilia population treated
      with factor prophylaxis: current status and future directions.
AB  - Routine infusions of factor VIII to prevent bleeding, known as prophylaxis, and
      other intensive therapies are being more broadly applied to patients with
      haemophilia. These therapies differ widely in replacement product usage, cost,
      frequency of venous access and parental effort. In order to address residual
      issues relating to recommendations, implementation, and evaluations of
      prophylaxis therapy in persons with haemophila, a multinational working group was
      formed and called the International Prophylaxis Study Group (IPSG). The group was
      comprised of haemophilia treaters actively involved in studies of prophylaxis
      from North America and Europe. Two expert committees, the Physical Therapy (PT)
      Working Group and the Magnetic Resonance Imaging (MRI) Working Group were
      organized to critically assess existing tools for assessment of joint outcome.
      These two committees independently concluded that the WFH Physical Examination
      Scale (WFH PE Scale) and the WFH X-ray Scale (WFH XR Scale) were inadequately
      sensitive to detect early changes in joints. New scales were developed based on
      suggested modifications of the existing scales and called the Haemophilia Joint
      Health Score (HJHS) and the International MRI Scales. The new scales were
      piloted. Concordance was measured by the intra-class correlation coefficient of
      variation. Reliability of the HJHS was excellent with an inter-observer co
      efficient of 0.83 and a test-retest value of 0.89. The MRI study was conducted
      using both Denver and European scoring approaches; inter-reader reliability using
      the two approaches was 0.88 and 0.87; test-retest reliability was 0.92 and 0.93.
      These new PT and MRI scales promise to improve outcome assessment in children on
      early preventive treatment regimens.

PMID- 15479379
TI  - Towards the goal of prophylaxis: experience and treatment strategies from Sweden,
      France and Hungary.
AB  - The only form of haemophilia treatment that is able to prevent arthropathy and
      other consequences of bleeding symptoms in patients with severe haemophilia is
      prophylaxis started at an early age (primary prophylaxis). It is also highly
      beneficial for the psychological and social wellbeing of patients and their
      families. Scientific institutions and international organizations such as WHO,
      the World Federation of Hemophilia (WFH) and the National Haemophilia Foundation
      (NHF) have recommended that prophylaxis be considered optimum therapy. This paper
      discusses the barriers to prophylaxis, such as the perceived need, costs and
      availability, and difficulty of venous access, and describes the authors'
      experiences with the therapy.

PMID- 15479380
TI  - Optimizing factor prophylaxis for the haemophilia population: where do we stand?
AB  - The hallmark of severe haemophilia, defined as a circulating level of factor (F)
      VIII (haemophilia A cases) or FIX (haemophilia B cases) of < 1%, is recurrent
      bleeding into muscles and joints (haemarthroses) from an early age of life. The
      inevitable result of such bleeding is progressive joint damage, leading to
      disabling arthritis that is typically evident within the first 2 decades of life
      in people with haemophilia who have limited or no access to regular factor
      replacement therapy, or those in whom factor replacement therapy is ineffective
      because of the presence of high-titre inhibitors. For children with severe
      haemophilia and no evidence of inhibitors, the unwanted musculoskeletal
      complications of severe haemophilia can be effectively prevented by the early
      initiation of a programme of long-term factor prophylaxis. In order to achieve
      the best outcome (a perfect musculoskeletal status for age) the programme of
      prophylaxis should be started before the onset of joint damage (primary
      prophylaxis). The gold standard primary prophylaxis regimen (the Malmo protocol)
      was pioneered and tested in Sweden and involves the infusion of 20-40 IU of FVIII
      per kg body weight on alternate days (minimum three times per week) for
      haemophilia A cases, and 20-40 IU kg(-1) of FIX twice weekly for haemophilia B
      cases. This protocol is, however, demanding on peripheral veins and very
      expensive. Modifications of the parent protocol such as starting primary
      prophylaxis with once-weekly infusions via peripheral veins with rapid escalation
      to full-dose prophylaxis or dose escalation based on frequency of bleeding are
      increasingly implemented in haemophilia treatment centres in countries that can
      afford the high cost of such programmes. These modified programmes can be
      achieved in the majority of young children with severe haemophilia without the
      need for central venous access devices (e.g. Port-a-Caths) and with avoidance of
      device-associated complications such as infection and thrombosis. In at least one
      centre, experience with arteriovenous fistulae as a strategy to ensure reliable
      venous access is being accumulated. The issues of compliance (adherence) to
      recommended prophylaxis protocols and when, if ever, to stop a programme of
      primary prophylaxis once started are real and require ongoing prospective
      studies. Such studies should incorporate outcome measures such as health-related
      quality-of-life and economic analyses.

PMID- 15479381
TI  - Essential issues of laboratory investigation for patients with haemophilia and
      bleeding disorders.
AB  - Apart from history-taking and physical examination, laboratory investigation is
      one of the essential issues for the definite diagnosis of haemophilia and
      bleeding disorders. The limited resources of medical personnel, equipment and
      reagents should be shared among several departments in the hospital, especially
      for serving patients with common genetic diseases such as thalassemia and
      haemoglobinopathies. Medical personnel require appropriate training to expand
      their skills in laboratory techniques. Laboratory procedures can be created,
      modified and simplified using locally produced and shared equipment. Molecular
      genetic studies can also be set up at different levels of hospital service using
      simple, rapid and low-cost methods. Finally, a system of periodic external
      quality control will guarantee the accuracy of laboratory results.

PMID- 15479382
TI  - Monitoring haemophilia severity and treatment: new or old laboratory tests?
AB  - Testing of factor levels is desirable for a number of reasons, including
      diagnosis of the level of severity of the disease, and the efficacy of factor
      replacement therapy. The older methods comprised the one-stage, two-stage, and
      chromogenic methods, and newer methods, including the thrombin generation test,
      are now available. This paper outlines the use of these methods and problems
      associated with them.

PMID- 15479383
TI  - What is a cure and how do we get there?
AB  - The absence of adequate treatment for most of the world's 400 000 individuals
      with haemophilia makes the development of a cure compelling. Advances in the
      basic molecular sciences over the past 20 years have resulted in the feasibility
      of curing haemophilia through the application of gene therapy. However, the
      reality of this therapeutic strategy is highly complex. In addition, challenges
      to achieving a cure exist beyond the basic scientific hurdles. Thoughtful
      attention must also be given to a number of interrelated issues, including
      ethical considerations in patient recruitment, informed consent and geographical
      variables of global clinical trials. The global inequalities in healthcare mean
      that the ethics of international medical research, especially when it includes
      countries where people usually do not receive quality care, become much more
      complicated. The majority of haemophiliacs lives in developing countries and is a
      valuable resource of human subjects who could be enrolled in clinical trials.
      When recruiting subjects globally, investigators must be ever mindful that the
      patient population is a precious resource, which must be treated with respect and
      care. This presents a major challenge for investigators engaged in trials of
      haemophilia gene therapy to ensure that the informed consent process is current
      and comprehensive, that therapeutic misconceptions are appropriately managed, and
      that the roles of the researcher and physician are clear. Global clinical gene
      therapy trials are an important and appropriate component in the quest to achieve
      a cure for haemophilia. When trials follow identical internationally accepted
      standards, a successful outcome can be achieved for trials including developing
      countries, if country specific cultural and economic aspects are considered.

PMID- 15479384
TI  - Preclinical and clinical gene therapy for haemophilia.
AB  - The goal of all haemophilia therapy is to prevent bleeding and its associated
      complications. Replacement by factor concentrates can only ever be suboptimum,
      and efforts are being made to correct the genetic cause of the disorder.
      Haemophilia is an ideal candidate for gene therapy, as it is caused by mutations
      in a single gene. A number of vectors have been used in an attempt to obtain
      therapeutic levels of factor VIII and factor IX in animal models, with some
      success. A number of phase 1 clinical trials have been conducted, and, although
      connection of the bleeding disorder was neither complete nor long-lasting, they
      do offer hope for a permanent gene-therapy cure for the disease.

PMID- 15479385
TI  - Preimplantation genetic diagnosis: new reproductive options for carriers of
      haemophilia.
AB  - Preimplantation genetic diagnosis for haemophilia offers couples at risk for
      transmitting the condition the opportunity to embark on a pregnancy knowing that
      the embryo is unaffected by the disease. The technique aims to increase the range
      of reproductive options available to these couples and remove the need for
      invasive prenatal diagnosis and the difficult decision on whether to terminate an
      affected pregnancy. This aims to reduce the anxiety associated with reproduction
      often seen in these couples. Patients undergo a cycle of in vitro fertilization
      followed by embryo biopsy. The single blastomeres are then analysed using
      fluorescent in situ hybridization to detect the sex of the embryo, and only
      female embryos are transferred to the uterus. Recently a PCR based approach has
      allowed specific mutation detection, and therefore the transfer of unaffected
      male and female embryos.

PMID- 15479386
TI  - Molecular basis of haemophilia A.
AB  - Technologies in molecular biology have greatly advanced the knowledge regarding
      the origin of haemophilia A and the physiology of the factor VIII (FVIII)
      protein. A variety of different mutations in the FVIII gene have been identified
      and their effects on the FVIII protein described. It has been shown that the
      frequency of haemophilia A is due to a high mutation rate predominantly in male
      germ cells. A significant proportion is originating de novo in early
      embryogenesis from somatic mutations, a finding that has implications for genetic
      counselling. The life-cycle of the FVIII protein and its structure-function
      relationships are continuously clarified. Most recently it has been shown that
      FVIII clearance from the circulation is mediated by the low-density lipoprotein
      receptor-related protein (LRP) and cell-surface heparan sulphate proteoglycans
      (HSPGs). These findings raise hope for novel recombinant FVIII molecules with
      prolonged half-life that may improve therapies for haemophlia A.

PMID- 15479387
TI  - Inhibitors in haemophilia: clinical aspects.
AB  - Inhibitor development continues to be a severe complication worldwide of
      haemophilia therapy. Given the difficulties associated with the treatment of
      inhibitors in both the developed and the developing world, prediction and
      prevention of inhibitors following exposure to factor VIII or IX in the young
      child has become a management priority. Two different clinical approaches to
      minimizing or delaying inhibitor development are highlighted in this manuscript.
      Challenges in the therapy of existing inhibitors persist. However, the nature of
      the issues faced by physicians in the developed and developing worlds vary
      considerably. Both are discussed in this manuscript by representatives of both
      worlds, who face these challenges on a daily basis.

PMID- 15479389
TI  - The target joint.
AB  - Bleeding into the joints is the most common manifestation of severe
      haemophiliacs. Although it may resolve spontaneously or with treatment, some
      patients find that one particular joint has recurrent bleeding; this is termed a
      target joint. Recurrent bleeding prevents the joint from regaining its range of
      motion, muscle strength and normal appearance. These changes become permanent,
      leading eventually to osteoarthritis. A target joint requires urgent and
      comprehensive treatment, especially in young patients, if permanent damage is to
      be prevented. Treatment with factor concentrate prophylaxis and physiotherapy can
      help to prevent new bleeds and allow the synovitis to resolve, but for persistent
      synovitis, synovectomy is recommended. The target ankle joint is a special
      challenge as it often develops in very young children when the articular
      cartilage is susceptible and compliance with conservative treatment is difficult.

PMID- 15479388
TI  - Inhibitors in haemophilia: pathophysiology.
AB  - Development of inhibitors to coagulation factors is one of the major problems
      faced by people with haemophilia. Up to a third of patients, following treatment
      with factor concentrates, will develop an antibody (inhibitor) to that factor,
      rendering it inactive, and leaving the patient at risk from life-threatening
      bleeding. Evidence shows that this immune response is T-cell-dependent, but as
      yet, the epitopes responsible have not been identified. Risk for inhibitor
      development is highest within the first 50 days of treatment, with reactions
      being rare after 200 days. The risk is mediated by the major histocompatibility
      complex class of the patient, and by mutations in the factor VIII genotype, with
      large deletions conferring greatest risk.

PMID- 15479390
TI  - Functional recovery after bleeding episodes in haemophilia.
AB  - Haemophilia is characterized by intra-articular and intramuscular bleeding
      episodes. Although much work has been carried out into post-bleeding mechanisms
      in both synovial joints and muscles, the picture is not yet clear. A firm post
      bleeding rehabilitation protocol is of utmost importance for people with
      haemophilia. The use of the International Classification of Functioning
      Disability and Health reveals that information worldwide is on body level,
      whereas the goals of patients with haemophilia implicitly aim at optimal
      functional recovery. This interferes much more with activities and participation
      in society. The Functional Independence Score for Haemophilia and the Post
      bleeding Protocol Based on Functional Milestones are examples of post-bleeding
      approaches that deal more with function. Two cases will emphasize the value of
      this approach.

PMID- 15479391
TI  - Risks and benefits of sports and fitness activities for people with haemophilia.
AB  - Physical activity is a key component of a healthy lifestyle. Exercise and
      physical activity have been shown to help maintain a healthy body weight, reduce
      stress, increase self-esteem and feelings of wellbeing, control blood pressure,
      and prevent heart disease and diabetes. Children with haemophilia may feel
      restricted from competing in sports through parental concern or pain and
      difficulty in moving, or they may rebel against such restrictions, thus leaving
      themselves open to serious injury. Several groups have attempted to classify
      sports activities with regard to the level of risk involved; however, these are
      not consistent. It is important to match the child's abilities with the sport in
      which they want to take part, and suggest alternatives if this is not possible.
      Prevention of injury should not depend solely on use of factor concentrates.

PMID- 15479392
TI  - von Willebrand disease: laboratory aspects of diagnosis and treatment.
AB  - von Willebrand disease is the most common inherited bleeding disorder in humans.
      VWD can be classified into three major types, designated Types 1, 2 and 3; Type 2
      can be further separated into subtypes 2A, 2B, 2M and 2N. The diagnosis of VWD
      requires a personal and family history of bleeding and confirmation by laboratory
      analysis. Although Types 2 and 3 are relatively straightforward to diagnose,
      there may be a risk of overdiagnosis of Type 1 because of an overlap within the
      normal range. We also report on the clinical profile and diagnosis of VWD in a
      South American cohort of patients and on the in vitro characteristics of some
      factor concentrates available for treatment of VWD.

PMID- 15479393
TI  - Clinical diagnosis of von Willebrand disease.
AB  - von Willebrand disease (VWD) is the most frequent inherited bleeding disorder and
      is caused by quantitative (Types 1 and 3) or qualitative (Type 2) defects of von
      Willebrand factor (VWF). VWD is inherited by autosomal dominant or recessive
      pattern, but women with milder VWD forms seem to be more symptomatic than men.
      Mild VWD forms are both under- and misdiagnosed. The clinical expression of VWD
      is usually mild in Type 1, increasing in severity in Types 2 and 3. Mucocutaneous
      bleeding (epistaxis, menorrhagia) is a typical manifestation of the disease, and
      bleeding after dental extraction is the most frequent postoperative bleeding
      type. Because FVIII levels are usually only slightly reduced in most VWD types,
      spontaneous haemarthroses or haematomas are rare in VWD Types 1, 2A and 2B,
      whereas in Type 3 the severity of bleeding may resemble haemophilia. In Type 1
      VWD, bleeding after delivery is rare because FVIII/VWF levels become normal at
      the end of pregnancy. Post-operative bleeding may not occur in Type 1 VWD
      patients, but in Type 3 VWD, prophylaxis is always required. Only a few
      retrospective studies on clinical diagnosis of VWD are available. In the 1234
      cases enrolled by an Italian retrospective study, diagnosis of Types 1, 2 and 3
      VWD occurred in young adults (83%), mainly in women (57%). Mucosal bleeding (64%)
      was more frequent than haematomas or haemarthrosis (15%), and 63% of patients did
      not require transfusions. In a more recent Italian prospective study (815/1234
      cases observed for 1 year in 6/16 Italian centres), only 147 (18%) VWD patients
      showed bleeding episodes (n = 318) and minor or major surgeries (n = 87).

PMID- 15479394
TI  - How to evaluate phenotype-genotype relationship in rare coagulation haemorrhagic
      disorders: examples from FVII deficiency.
AB  - The study of the molecular pathogenesis of several single-gene disorders, such as
      coagulation-factor deficiencies, has revealed the variability of phenotypic
      expression, even of the same mutations in single genes. These studies underline
      the complexity of research dealing with the definition of the molecular bases of
      disorders. Sequence variations provide only the starting point to define
      pathological genotype-phenotype relationships.

PMID- 15479395
TI  - Clinical picture and management of congenital factor VII deficiency.
AB  - In patients with congenital FVII deficiency, bleeding manifestations and clinical
      presentation vary widely, ranging from asymptomatic subjects to patients with
      haemorrhages that may cause important handicaps. Owing to menorrhagia, which
      occurs in about two-thirds of women of fertile age, bleeding is more frequent in
      women than in men. Gum bleeding and easy bruising are also more frequent in
      females. FVII:C levels are not a good predictor of bleeding tendency as there is
      a wide overlap between bleeders and asymptomatic patients. We propose a three
      grade system of classification based on clinical considerations. Therapy for
      congenital FVIII bleeding is discussed, with the advantages and disadvantages of
      each treatment, and the suggested single dose given.

PMID- 15479396
TI  - New observations on factor XI deficiency.
AB  - Factor (F) XI is an injury-related bleeding tendency that commonly occurs when
      trauma involves tissues rich in fibronolytic activators. Severe FXI deficiency is
      defined when the activity of FXI in plasma is less than 15 U dL(-1). The disorder
      is inherited as an autosomal recessive trait manifesting in homozygotes or
      compound heterozygotes, and infrequently in heterozygotes. So far 53 mutations in
      the gene of FXI have been described and four of them were found to be prevalent
      in Ashkenazi Jews, Iraqi Jews, Basques or the English population. For each of the
      four mutations a founder effect was discerned. Inhibitors can develop in patients
      with FXI level < 1U dL(-1) who were exposed to plasma which seriously complicates
      their management during surgery. No correction of a prolonged aPTT by normal
      plasma is indicative of the presence of an inhibitor. In contrast to patients
      with haemophilia A, severe FXI deficiency provides no protection against
      myocardial infarction. In patients with severe FXI deficiency undergoing surgery,
      fresh frozen plasma is the treatment of choice. FXI concentrates can also be used
      but cause thrombosis in approximately 10% of patients, particularly those with
      cardiovascular disease. Recombinant FVIIa has successfully prevented bleeding
      during or after surgery in patients with FXI inhibitors.

PMID- 15479397
TI  - Acquired bleeding disorders: the impact of health problems in the developing
      world.
AB  - Several acquired bleeding disorders in the developing world have impacts on
      health, including late vitamin K deficiency bleeding (VKDB) in infants, dengue
      haemorrhagic fever (DHF), and malaria. This paper describes their clinical
      manifestations, mechanisms involved, and treatment.

PMID- 15479398
TI  - The role of haemophilia treatment centres in providing services to women with
      bleeding disorders.

PMID- 15479399
TI  - Human immunodeficiency and hepatitis virus infections and their associated
      conditions and treatments among people with haemophilia.
AB  - Treatment with contaminated plasma products before 1990 resulted in extraordinary
      prevalence rates of human immunodeficiency virus (HIV) and hepatitis B and C
      viruses (HBV, HCV). In the Second Multicentre Haemophilia Cohort Study (MHCS-II)
      during 2001-03, 30% of HCV-seropositive survivors had HIV and 4.6% were HBV
      carriers. Highly active antiretroviral therapy (HAART) radically altered the
      consequences of HIV/HCV coinfection. Whereas opportunistic infections
      predominated previously, current major complications are liver failure and
      bleeding (exacerbated by decreased clotting factor synthesis, hypersplenic
      thrombocytopenia, and oesophageal varices). Most HIV-positives in MHCS-II were
      HIV RNA-negative and had > 200 CD4(+) cells microL(-1), but only 59% were on
      HAART. With HIV, especially after 41 years of age, liver disease was apparent
      (jaundice in 5%, ascites 7%, hepatomegaly 9%, splenomegaly 19%). HAART increases
      survival but may contribute to various comorbidities. Without HIV, sustained HCV
      clearance is obtained in > 50% with combined pegylated interferons plus
      ribavirin, but data in haemophilic populations, especially with HIV, are limited.
      In MHCS-II, HCV RNA negativity was 41% following standard interferon plus
      ribavirin; among interferon-naive participants (implying spontaneous HCV
      clearance), HCV RNA negativity was 12% with and 25% without HIV. Without HIV,
      spontaneous HCV clearance was much more likely with early age at infection and
      particularly with recent birth (late 1970s or early 1980s) but not with bleeding
      propensity or its treatment. Most (72%) participants had received no anti-HCV
      therapy. Hepatic and haematological conditions are likely to increase during the
      coming years unless most adult haemophiliacs are successfully treated for HIV,
      HCV or both.

PMID- 15479400
TI  - Hepatitis C in haemophilia: lights and shadows.
AB  - Hepatitis C is a major cause of morbidity and mortality in haemophiliacs who
      received clotting factor concentrates before the availability of virus
      inactivated factors in the mid-1980s. Early studies gave conflicting indications
      as to the severity of hepatitis C (originally termed non-A non-B hepatitis), as
      mild, slowly progressive hepatitis was documented in several infants and young
      adults with haemophilia who were examined with repeat liver biopsies, whereas
      more progressive hepatitis and cirrhosis was documented in others. One major
      point of dispute was whether these discrepancies could in part be accounted for
      by epidemiological differences among studies, as hepatitis C acquired early in
      life may initially run a benign course and later worsen owing to spontaneous
      recrudescence of hepatitis or interference with such comorbidity factors as
      alcohol abuse or infection with the human immunodeficiency virus (HIV). In the
      mid 1990s, the latter infection overshadowed hepatitis C as a cause of death in
      this patient population. Because hepatocellular carcinoma is emerging as an
      important complication in haemophiliacs with long-standing hepatitis C virus
      (HCV) infection who survived HIV infection, and because of recent advances in
      treating HIV, morbidity and mortality associated with chronic hepatitis C have
      regained emphasis amongst haemophiliacs. The development of newer interferon
      based therapies provides an opportunity for modifying the natural history of HCV
      infection in a substantial number of haemophilic patients.

PMID- 15479401
TI  - Dose and outcome of care in haemophilia--how do we define cost-effectiveness?
AB  - Severe haemophilia (factor [F]VIII/FIX activity < 0.01 IU mL(-1)) is
      characterized by repeated haemarthroses resulting in severe arthropathy in
      adulthood. In 1958, Professor Nilsson in Sweden introduced prophylactic infusions
      with clotting factor concentrates at regular intervals in order to maintain
      clotting factor levels above 0.01 IU mL(-1) and to prevent bleeding. Since then,
      evidence of the long-term beneficial effects of prophylactic treatment for severe
      haemophilia has been increasing and it has become the recommended treatment
      strategy for children with severe haemophilia by both the World Health
      Organization and the US National Hemophilia Foundation Medical and Scientific
      Advisory Committee. However, the implementation of this recommendation has been
      hampered by issues of cost and venous access. The high costs of prophylaxis have
      largely prevented its use in major parts of the world. The question therefore is
      whether the current models of replacement of clotting factor concentrates, while
      certainly being effective, are also optimal. Can the data on outcome at different
      levels of factor replacement be used to assess their cost-effectiveness?

PMID- 15479402
TI  - Microbiological status of piggery effluent from 13 piggeries in the south east
      Queensland region of Australia.
AB  - AIMS: To assist in the development of safe piggery effluent re-use guidelines by
      determining the level of selected pathogens and indicator organisms in the
      effluent ponds of 13 south-east Queensland piggeries. METHODS AND RESULTS: The
      numbers of thermotolerant coliforms, Campylobacter jejuni/coli, Erysipelothrix
      rhusiopathiae, Escherichia coli, Salmonella and rotavirus were determined in 29
      samples derived from the 13 piggeries. The study demonstrated that the 13 final
      effluent ponds contained an average of 1.2 x 10(5) colony-forming units (CFU) 100
      ml(-1) of thermotolerant coliforms and 1.03 x 10(5) CFU 100 ml(-1) of E. coli.
      The Campylobacter level varied from none detectable (two of 13 piggeries) to a
      maximum of 930 most probable number (MPN) 100 ml(-1) (two of 13 piggeries).
      Salmonella was detected in the final ponds of only four of the 13 piggeries and
      then only at a low level (highest level being 51 MPN 100 ml(-1)). No rotavirus
      and no Erysip. rhusiopathiae were detected. The average log10 reductions across
      the ponding systems to the final irrigation pond were 1.77 for thermotolerant
      coliforms, 1.71 for E. coli and 1.04 for Campylobacter. CONCLUSIONS: This study
      has provided a baseline knowledge on the levels of indicator organisms and
      selected pathogens in piggery effluent. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      knowledge gained in this study will assist in the development of guidelines to
      ensure the safe and sustainable re-use of piggery effluent.

PMID- 15479403
TI  - Quantification and prevalence of Salmonella in beef cattle presenting at
      slaughter.
AB  - AIMS: A survey to determine the prevalence and numbers of Salmonella in beef
      cattle presented for slaughter at abattoirs across Australia was conducted
      between September 2002 and January 2003. METHODS AND RESULTS: Automated
      immunomagnetic separation (AIMS) was used for detection and isolation of
      Salmonella enriched from cattle faeces. Salmonella were enumerated from positive
      samples using a combination of the Most Probable Number (MPN) technique and AIMS.
      A total of 310 faecal samples were tested, 155 were from lot-fed cattle and 155
      from grass-fed cattle. Salmonella spp. were isolated from 21 (6.8%) of the cattle
      and the prevalence amongst grass-fed cattle (4.5%) was not significantly
      different to that found in lot-fed cattle (9%). Counts of Salmonella in positive
      faeces varied from <3 MPN g(-1) of faeces to 2.8 x 10(3) MPN g(-1) and 71% of
      positive samples had counts <10 MPN g(-1) faeces. There was no significant
      difference in the mean log10 number of Salmonella in faeces of cattle from each
      production system. CONCLUSION: Low numbers of beef cattle were found to shed
      Salmonella at the time of slaughter and the prevalence and the associated faecal
      concentrations did not vary significantly with the pre-slaughter production
      system (grass or lot feeding). The faecal concentration of Salmonella in the
      majority of faeces was low (<10 MPN g(-1)) with few high concentrations up to 3 x
      10(3) MPN g(-1), suggesting there may be a low risk of carcase contamination.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Beef cattle do not appear to be a major
      source of entry of Salmonella into the human food chain and the quantitative
      information contained in this study can be used in quantitative assessments of
      the associated risk of human salmonellosis.

PMID- 15479404
TI  - Utilization of AFLP markers for PCR-based identification of Aspergillus
      carbonarius and indication of its presence in green coffee samples.
AB  - AIMS: The objective of this work was to test whether ochratoxin A (OTA)
      production of Aspergillus niger and A. carbonarius is linked to a certain
      genotype and to identify marker sequences with diagnostic value aiding
      identification of A. carbonarius, a fungus of major concern regarding OTA
      production in food and food raw materials. METHODS AND RESULTS: Aspergillus niger
      and A. carbonarius were isolated mainly from Brazilian coffee sources. The
      ability of isolates to produce OTA was tested by thin layer chromatography (TLC).
      Strains were genetically characterized by AFLP fingerprinting and compared with
      each other and with reference strains. Cluster analysis of fingerprints showed
      clear separation of A. niger from A. carbonarius strains. To obtain marker
      sequences, AFLP fragments were isolated from silver stained polyacrylamide gels,
      cloned and sequenced. Sequences obtained were used to develop species- specific
      PCR primers for the identification of A. carbonarius in pure culture and in
      artificially and naturally infected samples of green coffee. CONCLUSIONS: No
      clear correlation between genetic similarity of the strains studied and their
      potential to produce OTA was found. The PCR assays designed are a useful and
      specific tool for identification and highly sensitive detection of A.
      carbonarius. SIGNIFICANCE AND IMPACT OF THE STUDY: The developed PCR assays allow
      specific and sensitive detection and identification of A. carbonarius, a fungus
      considered to be one of the major causative agents for OTA in coffee and grape
      derived products. Assays may provide powerful tools to improve quality control
      and consumer safety in the food processing industry.

PMID- 15479405
TI  - Detection and quantification of Brettanomyces bruxellensis and 'ropy' Pediococcus
      damnosus strains in wine by real-time polymerase chain reaction.
AB  - AIMS: Brettanomyces bruxellensis is a well-known wine spoilage yeast that causes
      undesirable off-flavours. Likewise, glucan-producing strains of ropy Pediococcus
      damnosus are considered as spoilage micro-organisms because the synthesis of
      glucan leads to an unacceptable viscosity of wine. METHODS AND RESULTS: We
      developed a real-time PCR method to detect and quantify these two spoilage micro
      organisms in wine. It is based on specific primer pairs for amplification of
      target DNA, and includes a melting-curve analysis of PCR products as a
      confirmatory test. CONCLUSIONS: The detection limit in wine was 10(4) CFU ml(-1)
      for B. bruxellensis and 40 CFU ml(-1) for ropy Pediococcus damnosus. The real
      time PCR proved to be reliable for the early, sensitive detection and
      quantification of B. bruxellensis and ropy P. damnosus in wine. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The real-time PCR-based method described in this study
      provides a new tool for monitoring spoilage micro-organisms in wine. Time
      consuming culture and colony isolation steps are no longer needed, so winemakers
      can intervene before spoilage occurs.

PMID- 15479406
TI  - Application of antimicrobial ice for reduction of foodborne pathogens
      (Escherichia coli O157:H7, Salmonella Typhimurium, Listeria monocytogenes) on the
      surface of fish.
AB  - AIMS: The efficacy of antimicrobial ice was evaluated for the reduction of
      foodborne pathogens on the surface of fish. METHODS AND RESULTS: Antimicrobial
      ice containing chlorine dioxide (ClO2) was utilized to control foodborne
      pathogens in laboratory media and on fish skin. Escherichia coli O157:H7,
      Salmonella serotype Typhimurium and Listeria monocytogenes strains were treated
      with antimicrobial ice for 30 min on plates of selective agar and for 120 min on
      fish skin at room temperature, and then incubated for enumeration. After
      treatment with 100 ppm ClO2 for 30 min, 5.4, 4.4 and 3.2 log10 reduction was
      obtained with E. coli O157:H7, Salm. Typhimurium and L. monocytogenes on
      laboratory media, respectively. When antimicrobial ice (100 ppm ClO2) was applied
      to fish skin for 120 min, total reduction of E. coli O157:H7, Salm. Typhimurium
      and L. monocytogenes was 4.8, 2.6 and 3.3 log10, respectively. CONCLUSION: The
      initial load of foodborne pathogens was reduced by antimicrobial ice and the
      lowered microbial level was maintained during treatment. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The application of antimicrobial ice is a simple and effective
      method for the safe preservation of fish.

PMID- 15479407
TI  - Hepatitis A virus attachment to agri-food surfaces using immunological,
      virological and thermodynamic assays.
AB  - AIMS: This study was designed to investigate the ability of hepatitis A virus
      (HAV) to attach to various food contact surfaces. METHODS AND RESULTS: HAV
      attachment was demonstrated after elution of attached viruses from solid surfaces
      by an immunofluorescent method using anti-HAV-specific antibodies and confocal
      microscopy. Attachment and survival of HAV on stainless steel, copper, polythene
      and polyvinyl chloride (PVC) at 20 and 4 degrees C after 2 and 4 h were
      quantified by plaque assay. HAV was shown to attach almost instantaneously to all
      four surfaces tested. Attachment of HAV depended on initial viral concentration
      and was slightly greater at 4 degrees C. The total surface energy (gammaTOT),
      nonpolar Lifshitz-Van der Waals (gammaLW) and polar short range (gammaSR)
      hydrogen-bonding components for HAV and each surface as well as total free energy
      of the system were determined by contact angle measurements using an extended
      Young equation [Young (1805) Philosophical Transactions of The Royal Society
      (London) 95, 65-87). The calculation of these parameters predicted the favourable
      conditions for attachment of HAV to all four surfaces tested. CONCLUSION: HAV
      particles attach to stainless steel, copper, polythene and PVC at 20 and 4
      degrees C and the total free energy of the interaction is optimal for this
      attachment. SIGNIFICANCE AND IMPACT OF THE STUDY: Comprehension of viral
      attachment to the solid surfaces will permit to successfully disinfect these
      surfaces and to establish a better surveillance programme for control of viral
      food-borne illnesses.

PMID- 15479408
TI  - A flow cytometric technique for quantification and differentiation of bacteria in
      bulk tank milk.
AB  - AIMS: The present study describes a flow cytometric technique for quantification
      and differentiation of bacteria in bulk tank milk according to the main cause of
      elevated counts. METHODS AND RESULTS: A total of 75 Danish bulk tank milk samples
      exceeding the grading level of 3.0 x 10(4) CFU ml(-1) were examined by both flow
      cytometry and traditional microbiological analyses. The correlation coefficient
      (r) between the two methods was 0.71. For the differential analyses of the
      dominant bacterial populations four different parameters were used to give a
      species-characteristic pattern. The four parameters were as follows: staining
      with Oregon Green conjugated wheat germ agglutinin that binds to the cell wall of
      bacteria, staining with hexidium iodide that binds to all bacterial DNA, the flow
      cytometric forward scatter and the flow cytometric side scatter. Three regions in
      the flow cytometric plot were defined: region 1 includes bacteria mainly
      associated with poor hygiene, region 2 includes psychrotrophic hygiene bacteria
      and region 3 includes bacteria mainly related to mastitis. The ability of the
      flow cytometric technique to predict the main cause of elevated bacterial counts
      on routine samples was examined. Comparing these results with results obtained by
      traditional microbiological analyses for identification showed that for 81% of
      the samples the two techniques agreed on the main cause of an elevated bacterial
      count. CONCLUSIONS: The ability of the presented flow cytometric technique to
      enumerate and differentiate bacteria in bulk tank milk according to the main
      cause of elevated counts was demonstrated. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This study described the first step in development of a technique suitable for
      routine analyses of bulk tank milk samples. A technique indicating the main cause
      of an elevated count will enable the farmer to eliminate the contamination source
      within a short time limit.

PMID- 15479409
TI  - Purification and characterization of a lipopeptide produced by Bacillus
      thuringiensis CMB26.
AB  - AIMS: To isolate an antagonist for use in the biological control of
      phytopathogenic fungi including Colletotrichum gloeosporioides, then to purify
      and characterize the biocontrol agent produced by the antagonist. METHODS AND
      RESULTS: Bacteria that exhibited antifungal activity against the causative agent
      pepper anthracnose were isolated from soil, with Bacillus thuringiensis CMB26
      showing the strongest activity. A lipopeptide produced by B. thuringiensis CMB26
      was precipitated by adjusting the pH 2 with 3 n HCl and extracted using
      chloroform/methanol (2:1, v/v) and reversed-phase HPLC. The molecular weight was
      estimated as 1447 Da by MALDI-TOF mass spectrometry. Scanning electron and
      optical microscopies showed that the lipopeptide has activity against Escherichia
      coli O157:ac88, larvae of the cabbage white butterfly (Pieris rapae crucivora)
      and phytopathogenic fungi. The lipopeptide had cyclic structure and the amino
      acid composition was L-Glu, D-Orn, L-Tyr, D-allo-Thr, D-Ala, D-Val, L-Pro, and L
      Ile in a molar ratio of 3:1:2:1:1:2:1:1. The purified lipopeptide showed the same
      amino acid composition as fengycin, but differed slightly in fatty acid
      composition, in which the double bond was at carbons 13-14 (m/z 303, 316) and
      there was no methyl group. CONCLUSION: A lipopeptide was purified and
      characterized from B. thuringiensis CMB26 and found to be similar to the
      lipopeptide fengycin. This lipopeptide can function as a biocontrol agent, and
      exhibits fungicidal, bactericidal, and insecticidal activity. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Compared with surfactin and iturin, the lipopeptide from B.
      thuringiensis CMB26 showed stronger antifungal activity against phytopathogenic
      fungi. This lipopeptide is a candidate for the biocontrol of pathogens in
      agriculture.

PMID- 15479410
TI  - Amoebae in domestic water systems: resistance to disinfection treatments and
      implication in Legionella persistence.
AB  - AIMS: Monitoring of microbial changes during and after application of various
      disinfection treatments in a model domestic water system. METHODS AND RESULTS: A
      pilot-scale domestic water system consisting of seven galvanized steel re
      circulation loops and copper dead legs was constructed. Culture techniques,
      confocal laser scanning microscopy after fluorescent in situ hybridization and
      viability staining with the BacLight LIVE/DEAD kit were used for planktonic and
      biofilm flora monitoring. Before starting the treatments, the system was highly
      contaminated with Legionella pneumophila and biofilm populations mainly consisted
      of beta-proteobacteria. In the water and the biofilm of the loops, continuous
      application of chlorine dioxide (0.5 mg l(-1)), or chlorine (2.5 mg l(-1)) were
      very effective in reducing the microbial flora, including L. pneumophila.
      Heterotrophic bacteria, although strongly reduced, were still detectable after
      ozone application (0.5 mg l(-1)), whereas with monochloramine (0.5 mg l(-1)) and
      copper-silver ionization (0.8/0.02 mg l(-1)), the contamination remained
      significantly higher. Monochloramine and copper-silver did not remove the
      biofilm. During copper-silver application, Legionella re-growth was observed.
      Only chlorine dioxide led to detectable effects in the dead leg. Amoebae could
      not be eliminated, and after interrupting the treatments, L. pneumophila quickly
      recovered their initial levels, in all cases. CONCLUSIONS: Chlorine dioxide,
      applied as a continuous treatment, was identified in this study as the most
      efficient for controlling L. pneumophila in a domestic water system. Chlorine
      dioxide showed a longer residual activity, leading to improved performance in the
      dead leg. Amoebae resisted to all the treatments applied and probably acted as
      reservoirs for L. pneumophila, allowing a quick re-colonization of the system
      once the treatments were interrupted. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Control of microbial contamination requires maintenance of a constant
      disinfectant residual throughout the water system. Treatment strategies targeting
      free-living amoebae should lead to improved control of L. pneumophila. Such
      treatment strategies still have to be investigated.

PMID- 15479411
TI  - Premature Salmonella Typhimurium growth inhibition in competition with other Gram
      negative organisms is redox potential regulated via RpoS induction.
AB  - AIMS: To identify the role of oxidation-reduction (redox) potential in the
      premature growth inhibition and RpoS induction in Salmonella serotype Typhimurium
      in competitive growth experiments. METHODS AND RESULTS: Oxidation-reduction
      potential was measured throughout the growth of a minority population of Salm.
      Typhimurium in mixed cultures with other Gram-negative and Gram-positive
      organisms. A lux-based reporter was also used to evaluate RpoS activity in Salm.
      Typhimurium in competitor studies. In a mixed culture, the multiplication of a
      minority population of Salm. Typhimurium was inhibited when competing Gram
      negative organisms entered the stationary phase. This was not seen when the
      competing flora was Gram-positive. The change in redox potential during growth in
      mixed cultures was closely linked to the inhibition of Salm. Typhimurium growth
      by Gram-negative competitors. An artificially induced drop in redox potential
      earlier during growth in mixed cultures with Gram-negative organisms reduced the
      time to RpoS induction in Salm. Typhimurium and thus inhibited its multiplication
      prematurely. In contrast, RpoS induction and growth inhibition were prevented
      under high redox potential conditions. CONCLUSIONS: This work shows that the
      inhibitory activity of competitive organisms can be mediated through their effect
      on redox potential-regulated RpoS induction. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Redox potential is shown to be an important determinant of Salm.
      Typhimurium growth, an observation with practical implications both for its
      control and detection.

PMID- 15479412
TI  - The molecular diversity of the methanogenic community in a hypereutrophic
      freshwater lake determined by PCR-RFLP.
AB  - AIMS: To combine database-held sequence information with a programme of
      experimental molecular ecology to define the methanogenic community of a
      hypereutrophic lake by a PCR-restriction fragment length polymorphism (RFLP)
      analysis. METHODS AND RESULTS: Methanogen diversity in a hypereutrophic
      freshwater lake was analysed using 16S rDNA PCR-RFLP. Database-held 16S rRNA gene
      sequences for 76 diverse methanogens were analysed for specific restriction sites
      that permitted unequivocal differentiation of methanogens. Restriction digestion
      and agarose gel electrophoresis of the 16S rDNA from selected methanogen pure
      cultures generated observed restriction profiles that corroborated the expected
      patterns. This method was then tested by analysing methanogen diversity in
      samples obtained over 1 year from sediment and water samples taken from the same
      sampling site. CONCLUSIONS: Restriction analysis of the 16S rRNA gene sequences
      from 157 methanogen clones generated from lakewater and sediment samples showed
      that over 50% were similar to Methanoculleus spp. Furthermore, a total of 16 RFLP
      types (1-16) were identified, eight of which contained no cultured representative
      archaeal 16S rRNA gene sequences. SIGNIFICANCE AND IMPACT OF THE STUDY: This RFLP
      strategy provides a robust and reliable means to rapidly identify methanogens in
      the environment.

PMID- 15479413
TI  - Purification and properties of a novel glycine amino peptidase from Actinomucor
      elegans and its potential application.
AB  - AIMS: To study the properties and show the potential application of a glycine
      aminopeptidase from Actinomucor elegans. METHODS AND RESULTS: The enzyme was
      estimated to have molecular mass of 320 kDa by gel filtration and the subunit
      size of 56.5 kDa by SDS-PAGE. It hydrolysed glycine from substrate more
      efficiently than other amino acids. The optimal temperature for this enzyme was
      40 degrees C and at pH 8.0 it showed its highest activity. The Km and Kcat of the
      enzyme for glycine-beta-naphthylamine was 0.24 mm and 100.8 s(-1), respectively.
      Zinc, copper, cadmium and o-phenanthrolin suppressed almost all enzyme activities
      at the concentration of 1.0 mm. In the process of hydrolysing proteins, it could
      improve the protease activity considerably. CONCLUSIONS: It was a hexamer
      metalloenzyme which was specific for the substrates with glycinse residue at the
      N-terminal and some metal cations were needed to maintain its activity.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the properties of a
      novel aminopeptidase and shows its potential application in the process of the
      food industry.

PMID- 15479414
TI  - Cereulide, the emetic toxin of Bacillus cereus, is putatively a product of
      nonribosomal peptide synthesis.
AB  - AIMS: To determine if cereulide, the emetic toxin produced by Bacillus cereus, is
      produced by a nonribosomal peptide synthetase (NRPS). METHODS AND RESULTS: NC Y,
      an emetic strain of Bacillus cereus, was examined for a NRPS gene using PCR with
      primers recognizing a fragment of a NRPS gene from the cyanobacterium
      Microcystis. The amplicon was sequenced and compared with other gene sequences
      using BLAST analysis, which showed that the amplicon from strain NC Y was similar
      in sequence to peptide synthetase genes in other micro-organisms, including
      Bacillus subtilis and B. brevis, while no such sequence was found in the complete
      genome sequence of a nonemetic strain of B. cereus. Specific PCR primers were
      then designed and used to screen 40 B. cereus isolates previously implicated in
      outbreaks of foodborne illness. The isolates were also screened for toxin
      production using the MTT cell cytotoxicity assay. PCR and MTT assay screening of
      the B. cereus isolates revealed a high correlation between the presence of the
      NRPS gene and cereulide production. CONCLUSIONS: The results indicate that
      cereulide is produced by a NRPS complex. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This is the first study to provide evidence identifying the mechanism of
      production of cereulide, the emetic toxin of B. cereus. The PCR primers developed
      in the study allow determination of the potential for cereulide production among
      isolates of B. cereus.

PMID- 15479415
TI  - Eugenol stimulates lactate accumulation yet inhibits volatile fatty acid
      production and eliminates coliform bacteria in cattle and swine waste.
AB  - AIM: To determine how eugenol affects fermentation parameters and faecal
      coliforms in cattle and swine waste slurries stored anaerobically. METHODS AND
      RESULTS: Waste slurries (faeces:urine:water, 50:35:15) were blended with and
      without additives and aliquoted to triplicate 1-l flasks. Faecal coliforms were
      eliminated in cattle and swine waste slurries within 1 or 2 days with additions
      of eugenol at 10.05 mm (0.15%) and 16.75 mm (0.25%). At these concentrations
      volatile fatty acids (VFA) were reduced ca 70 and 50% in cattle and swine waste,
      respectively, over 6-8 weeks. Additionally, in cattle waste, eugenol stimulated
      the accumulation of lactate (>180 mm) when compared with thymol treatment (20 mm
      lactate). In swine waste, lactate accumulation did not occur without additives;
      eugenol and thymol stimulated lactate accumulation to concentrations of 22 and 32
      mm, respectively. CONCLUSIONS: Eugenol added to cattle waste may be more
      beneficial than thymol because not only does it effectively control faecal
      coliforms and odour (VFA production), it also stimulates lactate accumulation.
      This in turn, causes the pH to drop more rapidly, further inhibiting microbial
      activity and nutrient emissions. SIGNIFICANCE AND IMPACT OF THE STUDY: Plant
      essential oils have the potential to solve some of the environmental problems
      associated with consolidated animal feeding operations. Thymol and eugenol reduce
      fermentative activity, thus, have the potential to reduce emissions of greenhouse
      gases and odour, and curtail transmission of pathogens in cattle and swine
      wastes.

PMID- 15479416
TI  - Characterization of a thermostable recombinant beta-galactosidase from Thermotoga
      maritima.
AB  - AIMS: Characterization of a thermostable recombinant beta-galactosidase from
      Thermotoga maritima for the hydrolysis of lactose and the production of galacto
      oligosaccharides. METHODS AND RESULTS: A putative beta-galactosidase gene of
      Thermotoga maritima was expressed in Escherichia coli as a carboxyl terminal His
      tagged recombinant enzyme. The gene encoded a 1100-amino acid protein with a
      calculated molecular weight of 129,501. The expressed enzyme was purified by heat
      treatment, His-tag affinity chromatography, and gel filtration. The optimum
      temperatures for beta-galactosidase activity were 85 and 80 degrees C with oNPG
      and lactose, respectively. The optimum pH value was 6.5 for both oNPG and
      lactose. In thermostability experiments, the enzyme followed first-order kinetics
      of thermal inactivation and its half-life times at 80 and 90 degrees C were 16 h
      and 16 min, respectively. Mn2+ was the most effective divalent cation for beta
      galactosidase activity on both oNPG and lactose. The Km and Vmax values of the
      thermostable enzyme for oNPG at 80 degrees C were 0.33 mm and 79.6 micromol oNP
      min(-1) mg(-1). For lactose, the Km and Vmax values were dependent on substrate
      concentrations; 1.6 and 63.3 at lower concentrations up to 10 mm of lactose and
      27.8 mm and 139 micromol glucose min(-1) mg(-1) at higher concentrations,
      respectively. The enzyme displayed non-Michaelis-Menten reaction kinetics with
      substrate activation, which was explained by simultaneous reactions of hydrolysis
      and transgalactosylation. CONCLUSIONS: The results suggest that the thermostable
      enzyme may be suitable for both the hydrolysis of lactose and the production of
      galacto-oligosaccharides. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of
      this work contribute to the knowledge of hydrolysis and transgalactosylation
      performed by beta-galactosidase of hyperthermophilic bacteria.

PMID- 15479417
TI  - Amelioration in secretion of hyperthermostable and Ca2+ -independent alpha
      amylase of Geobacillus thermoleovorans by some polyamines and their biosynthesis
      inhibitor methylglyoxal-bis-guanylhydrazone.
AB  - AIM: Effect of polyamines and their biosynthesis inhibitors on the production of
      hyperthermostable and Ca2+ -independent alpha-amylase by Geobacillus
      thermoleovorans MTCC 4220. METHODS AND RESULTS: The alpha-amylase was produced in
      starch-yeast extract-tryptone (SYT) broth with different polyamines (PA) and
      polyamine biosynthesis inhibitors, methylglyoxal-bis-guanylhydrazone (MGBG) and
      cyclohexylammonium sulphate (CHA) at 70 degrees C. The bacterial pellets were
      obtained after growing G. thermoleovorans at different temperatures, and used in
      determining total PA. The cell-free culture filtrates were used in alpha-amylase
      assays. During growth, total polyamines in biomass increased till 2 h, and
      thereafter, decreased gradually. The total polyamine content was very high in the
      biomass cultivated at 55 degrees C when compared with that of higher
      temperatures. Enzyme titre enhanced up to 70 degrees C, and thereafter declined.
      Extracellular enzyme and protein levels declined in the presence of exogenously
      added PA. The intracellular enzyme titres, however, were higher in putrescine
      (put) and spermidine (spd) than in spermine (spm). Polyamine biosynthesis
      inhibitor, MGBG enhanced secretion of alpha-amylase in a laboratory fermentor as
      well as shake flasks, although CHA did not affect it. CONCLUSIONS: The
      intracellular accumulation of put in the presence of MGBG appeared to enhance
      synthesis and secretion of alpha-amylase. Extracellular enzyme and protein levels
      were low in the presence of exogenously added PA, but their intracellular levels,
      however, were higher in put and spd than in spm. SIGNIFICANCE AND IMPACT OF THE
      STUDY: A substantial increase in the synthesis and secretion of alpha-amylase was
      attained in G. thermoleovorans in the presence of polyamine biosynthesis
      inhibitor MGBG.

PMID- 15479418
TI  - Complete sequence of virulence plasmid pEIB1 from the marine fish pathogen Vibrio
      anguillarum strain MVM425 and location of its replication region.
AB  - AIMS: The aim of this study was to determine the whole DNA sequence of pEIB1, one
      pJM1-like virulence plasmid from Vibrio anguillarum MVM425 and locate the
      replication region. METHODS AND RESULTS: DNA sequence of virulence plasmid pEIB1
      from V. anguillarum MVM425 was determined using the methods of restriction
      endonuclease digestion, subcloning, and primer walking. The whole nucleotide
      sequence of pEIB1 comprises 66,164 bp, encoding 44 open reading frames (>400 bp)
      containing the genes of DNA replication, biosynthesis and regulation of the
      siderophore anguibactin and transport of ferric-anguibactin complexes. With no
      demonstrated replication origin, the Sau3AI partial digested plasmid DNA
      fragments of pEIB1 were ligated into the BamHI-fragment containing the kanamycin
      resistance gene (Kmr). For there is no effective transformation in V.
      anguillarum, the ligated DNA was first introduced into E. coli JM83, and the
      transfomants were selected for resistance to kanamycin. It was demonstrated with
      southern blotting and DNA sequencing that plasmid pEIB7 containing the Sau3AI DNA
      fragment of pEIB1 (from 12516 to 13957) has the ability to replicate in E. coli
      JM83 and V. anguillarum MVM425sh. The segregational stability of plasmid pEIB7
      kept in 100 and 4% in E. coli JM83 and V. anguillarum MVM425sh respectively when
      the cells were cultured in 200th generation. In following experiments, we also
      found that plasmid pEIB7 replicated at a middle-copy number of 10-40 in JM83,
      while at a high-copy number of 100-300 in MVM425sh. Moreover, pEIB7 can survive
      in V. alginolyticus, another fish pathogenic. CONCLUSIONS: With the whole DNA
      sequence of pEIB1 determining, it was found that pEIB1 showed microheterogeneity
      in its restriction endonuclease patterns with pJM1 though their DNA sequences had
      slight difference. According to the complete DNA sequence of pEIB1, its
      replication region was located from 12516 to 13957. And this replication region
      is compatible to pUC18 (pMB1), pKA3 (pSC101) and p15A: caiE (p15A). SIGNIFICANCE
      AND IMPACT OF THE STUDY: The worldwide vibriosis marine pathogen V. anguillarum
      strains contain common virulence, pJM1-like plasmids, independent on the
      geographical source. The pEIB1 was the second common virulence plasmid, which
      sequence was determined. Its sequence is highly homologous to pJM1 as they both
      encode biosynthesis and regulation of the siderophore anguibactin and transport
      of ferric-anguibactin complexes. Some interesting features as in pJM1 were also
      identified, such as transposon-like structures. So it can be deferred that the
      whole DNA sequences of virulent plasmid pEIB1 will be great helpful to future
      revealing these V. anguillarum virulence-related genes derived during evolution
      from transposition events or horizontal transfer of genes potentially originating
      in other organisms. Another result, replication region of pEIB1 locating is the
      first report about replication of pJM1-like plasmid. This work will be useful for
      researching pJM1-like plasmid replication mechanism in V. anguillarum.

PMID- 15479419
TI  - Biodiversity of Listeria monocytogenes sensitivity to bacteriocin-producing
      Carnobacterium strains and application in sterile cold-smoked salmon.
AB  - AIMS: The aim of this study was to demonstrate the inhibitory capacity of
      Carnobacterium strains against a collection of Listeria monocytogenes strains in
      cold-smoked salmon (CSS). METHODS AND RESULTS: Three bacteriocin-producing
      strains, Carnobacterium divergens V41, C. piscicola V1 and C. piscicola SF668,
      were screened for their antilisterial activity against a collection of 57 L.
      monocytogenes strains selected from the French smoked salmon industry, using an
      agar spot test. All the Listeria strains were inhibited but three different
      groups could be distinguished differing in sensitivity to the three
      Carnobacterium strains. However, C. divergens V41 always had the highest
      inhibitory effect. The antilisterial capacity was then tested in sterile CSS
      blocks co-inoculated with Carnobacterium spp. and mixtures of L. monocytogenes
      strains. C. divergens V41 was the most efficient strain, maintaining the level of
      L. monocytogenes at <50 CFU g(-1) during the 4 weeks of vacuum storage at 4 and 8
      degrees C, whatever the sensitivity of the set of L. monocytogenes strains.
      CONCLUSIONS: C. divergens V41 may be a good candidate for biopreservation in CSS.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A biopreservation strategy for CSS against
      the risk of L. monocytogenes was investigated using bacteriocin-producing lactic
      acid bacteria.

PMID- 15479420
TI  - Ochratoxin A removal in synthetic and natural grape juices by selected
      oenological Saccharomyces strains.
AB  - AIMS: To assess, for the first time the efficiency in removing ochratoxin A (OTA)
      from laboratory medium [yeast peptone glucose (YPG)], synthetic grape juice
      medium (SGM) and natural grape juice by viable and dead (heat and acid-treated)
      oenological Saccharomyces strains (five S. cerevisiae and one S. bayanus)
      compared with a commercial yeast walls additive. METHODS AND RESULTS: Levels of
      OTA during its interaction with six oenological Saccharomyces strains (five S.
      cerevisiae and one S. bayanus) or with a commercial yeast walls additive in YPG
      medium, in SGM or in natural grape juices was assessed by HPLC after appropriate
      extraction methods. A significant decrease of OTA levels in YPG medium and SGM
      was observed for many of the growing strains reaching a maximum of 45%, but no
      degradation products were detected. With both heat and acid pretreated yeasts,
      OTA removal was enhanced, indicating that adsorption, not catabolism, is the
      mechanism to reduce OTA concentrations. Adsorption was also improved when the
      yeast concentration was increased and when the pH of the medium was lower.
      Approximately 90% of OTA was bound rapidly within 5 min and up to 72 h of
      incubation with heat-treated cells of either S. cerevisiae or S. bayanus. A
      comparative study between heat-treated cells (HC) and commercial yeast walls (YW)
      (used as oenological additive), introduced at two different concentrations (0.2
      and 6.7 g l(-1)) in an OTA-contaminated grape juice, showed the highest
      efficiency by HC to adsorb rapidly within 5 min the total amount of the
      mycotoxin. CONCLUSIONS: Oenological S. cerevisiae and S. bayanus were able to
      remove ochatoxin A from synthetic and natural grape juices. This removal was
      rapid and improved by dead yeasts having more efficiency than commercial yeast
      walls. SIGNIFICANCE AND IMPACT OF THE STUDY: The efficiency of heat-treated
      yeasts to remove OTA gives a new hope for grape juice and must decontamination
      avoiding negative impacts on human health.

PMID- 15479421
TI  - Intermittent and persistent shedding of Escherichia coli O157 in cohorts of
      naturally infected calves.
AB  - AIMS: We conducted two short-term studies of cohorts of naturally infected calves
      to determine the prevalence and concentrations of Escherichia coli O157 shed in
      faeces. METHODS AND RESULTS: Two cohorts of calves were sampled; in the first
      study 14 calves were sampled up to five times a day for 5 days; in the second
      study a group of 16 separate calves were sampled once or twice a day for 15 days.
      All cattle within the two cohorts shed E. coli O157 at some point during the
      respective studies. In 18% of samples, E. coli O157 could only be isolated using
      immunomagnetic separation after an enrichment period, suggesting concentrations
      <250 CFU g(-1). The highest concentrations recorded were 6.7 x 10(5) and 1.6 x
      10(6) CFU g(-1) for studies 1 and 2 respectively. CONCLUSIONS: Persistent, high
      shedders (shedding >10(3) CFU g(-1)) were evident in both studies but, in the
      majority of calves, the pathogen was isolated intermittently. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The variable patterns of shedding have important
      implications for the design of appropriate sampling protocols and for gaining
      meaningful estimates of parameters used in mathematical models of transmission.

PMID- 15479423
TI  - Induction of the mar operon by miscellaneous groceries.
AB  - AIM: To investigate the potential of non-antibacterial consumer products to act
      as inducers of the multiple antibiotic resistance (mar) operon of Escherichia
      coli SPC105. METHODS AND RESULTS: Wells were cut into chemically defined agar
      medium (CDM) contained within Petri dishes. Molten agar slurries were prepared by
      mixing known quantities of 35 consumer products with molten CDM and these were
      pipetted into each well. Plates were overlaid with molten CDM (5 ml), containing
      40 microg ml(-1) X-gal and approx. 1000 CFU ml(-1) of an overnight culture of E.
      coli SPC105 containing a chromosomal marOII::lacZ fusion. After incubation (37
      degrees C, 24 h), plates were examined for zones of growth inhibition and the
      presence of a blue coloration, indicative of mar (marOII::lacZ) induction. Of the
      35 products tested (nine herbs and spices, 19 food and drinks and seven household
      products), 24 (69%) of the items produced inhibitory zones and 22 (63%) of the
      items induced mar expression. Apple puree was inhibitory but did not induce
      marOII::lacZ. Mustard, chilli and garlic were shown to be powerful inducers of
      marOII::lacZ. Overall six products were shown to be powerful marOII::lacZ
      inducers. None of these made hygiene claims. CONCLUSIONS: In addition to
      induction by specific biocides and antibiotics, mar is induced by the exposure of
      bacteria to natural substances, many of which are common to a domiciliary
      setting. SIGNIFICANCE AND IMPACT OF THE STUDY: Concern that the overuse of
      antibacterials within consumer products might select for mar-mediated resistance
      is shortsighted and fails to recognize the ubiquity of inducers in our
      environment.

PMID- 15479422
TI  - The relationship between concentration of a dual marker strain of Salmonella
      Typhimurium in bovine faeces and its probability of detection by immunomagnetic
      separation and culture.
AB  - AIMS: To modify a strain of Salmonella serotype Typhimurium to express unique
      marker traits and then define how the concentration of the marker in bovine
      faeces affects the probability of its detection by culture preceded by
      immunomagnetic separation (IMS). METHODS AND RESULTS: DNA encoding for the
      production of green fluorescent protein (gfp) and resistance to kanamycin was
      inserted into the bacterial chromosome of Salm. Typhimurium. Transposon insertion
      was demonstrated by Southern blot hybridization. Varying amounts of one
      electroporant (gfpSal-1) were inoculated into suspensions of bovine faeces and
      attempts made to isolate gfpSal-1 using a protocol based on pre-enrichment
      incubation, IMS and enrichment in selective media. Isolates of gfpSal-1 were
      differentiated from wild strains of Salmonella using fluorescence under u.v.
      light and expression of kanamycin resistance. A logistic and Gompertz function
      each derived from the dose-response data partially explained the observations
      with the fit of the Gompertz function judged to be superior. The 10, 50 and 90%
      limits of detection from the Gompertz function were estimated to be 1.92, 2.03
      and 2.27 CFU g(-1) respectively. CONCLUSIONS: Reliance on the traditional concept
      of 'limit of detection' could introduce unacceptable errors in the interpretation
      of test findings when the concentration of Salm. Typhimurium in bovine faeces
      (pooled or individual) is below ca 3 CFU g(-1) of faeces. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The dose-response curve can be used to aid the design of protocols
      for detecting Salmonella in individual and pooled faecal specimens. The
      experiments demonstrate that both reporter genes in tandem are useful for
      studying the performance of culture-based methods for detecting pathogens in
      faeces.

PMID- 15479424
TI  - Reduction of bacterial indicators and bacteriophages infecting faecal bacteria in
      primary and secondary wastewater treatments.
AB  - AIMS: To compare the suitability of various bacterial and viral indicators to
      assess the removal of faecal micro-organisms by primary and secondary wastewater
      treatment processes. METHODS AND RESULTS: The numbers of several bacterial
      indicators [faecal coliforms (FC), enterococci (ENT) and sulphite-reducing
      clostridia (SRC)] and bacteriophages (somatic coliphages, F-specific RNA phages
      and bacteriophages infecting Bacteroides fragilis strain RYC2056) were determined
      in incoming raw sewage and effluents from various primary and secondary
      wastewater treatment processes in several geographical areas. Reductions in the
      numbers of indicators were calculated as log10 reductions. Processes based on
      removal and mild disinfection, showed no significant differences in the
      elimination of any of the indicators tested or between geographical areas. In
      contrast, treatment processes that include strong microbial inactivation, such as
      lime-aided flocculation and lagooning, showed significant differences between the
      log10 reductions of the various micro-organisms studied, FC showing the highest
      reduction and spores of SRC and phages infecting B. fragilis the lowest.
      CONCLUSIONS: The microbial elimination performance of treatment processes based
      principally on removal and mild disinfection can be evaluated with a single
      indicator. In contrast, processes with additional disinfecting capabilities
      require more than one indicator for accurate evaluation of the treatment;
      bacteriophages are good candidates for use as second indicators. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Bacteriophages provide additional information for the
      evaluation of microbial elimination in some treatment plants. The easy, fast and
      cheap methods available for phage determination are feasible both in
      industrialized and developing countries.

PMID- 15479425
TI  - Distribution of six virulence factors in Aeromonas species isolated from US
      drinking water utilities: a PCR identification.
AB  - AIMS: To examine whether Aeromonas bacteria isolated from municipally treated
      water had virulence factor genes. METHODS AND RESULTS: A polymerase chain
      reaction-based genetic characterization determined the presence of six virulence
      factors genes, elastase (ahyB), lipase (pla/lip/lipH3/alp-1) flagella A and B
      (flaA and flaB), the enterotoxins, act, alt and ast, in these isolates. New
      primer sets were designed for all the target genes, except for act. The genes
      were present in 88% (ahyB), 88% (lip), 59% (fla), 43% (alt), 70% (act) and 30%
      (ast) of the strains, respectively. Of the 205 isolates tested only one isolate
      had all the virulence genes. There was a variety of combinations of virulence
      factors within different strains of the same species. However, a dominant strain
      having the same set of virulence factors, was usually isolated from any given tap
      in different rounds of sampling from a single tap. CONCLUSIONS: These results
      show that Aeromonas bacteria found in drinking water possess a wide variety of
      virulence-related genes and suggest the importance of examining as many isolates
      as possible in order to better understand the health risk these bacteria may
      present. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents a rapid method
      for characterizing the virulence factors of Aeromonas bacteria and suggests that
      municipally treated drinking water is a source of potentially pathogenic
      Aeromonas bacteria.

PMID- 15479426
TI  - Development of a multiplex PCR for the identification of Staphylococcus genus and
      four staphylococcal species isolated from food.
AB  - AIMS: To develop a multiplex PCR that allows the identification of bacteria
      belonging to the Staphylococcus genus and in particular to the species
      Staphylococcus xylosus, S. saprophyticus, S. epidermidis and S. aureus isolated
      from food manufacturing plants. METHODS AND RESULTS: Five primer pairs were used
      in the multiplex PCR, one specific to the Staphylococcus genus and four specific
      to S. xylosus, S. saprophyticus, S. epidermidis and S. aureus species. All the 31
      Staphylococcus reference strains yielded a specific PCR product with the genus
      specific primers. Staphylococcus xylosus, S. saprophyticus, S. epidermidis and S.
      aureus gave a specific PCR fragment with the corresponding species-specific
      primers. No amplification with the Kocuria, Macrococcus and Micrococcus strains
      was observed in our conditions. This multiplex PCR was performed on 30 strains of
      Gram-positive cocci isolated from different workshops and fermented sausages.
      Among them, 28 belonged to the Staphylococcus genus and 14 were identified to S.
      saprophyticus, four to S. xylosus, two to S. aureus and one to S. epidermidis.
      CONCLUSIONS: This multiplex PCR provided reliable and repeatable PCR results. It
      allowed the identification of a major part of the isolates, highlighting the
      predominance of the S. saprophyticus species in the workshops studied.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This tool is a useful way to screen the
      strains isolated from foodstuff and food environment and to monitor these species
      during the food processing.

PMID- 15479427
TI  - Application of genotypic and phenotypic analyses to commercial probiotic strain
      identity and relatedness.
AB  - AIMS: The objective of this study was to generate strain-specific genomic
      patterns of a bank of 67 commercial and reference probiotic strains, with a focus
      on probiotic lactobacilli. METHODS AND RESULTS: Pulsed-field gel electrophoresis
      (PFGE) was used as the primary method for strain differentiation. This method was
      compared with carbohydrate fermentation analysis. To supplement visual
      comparison, PFGE patterns were analysed quantitatively by cluster analysis using
      unweighted pair group method with arithmetic averages. SmaI, NotI and XbaI were
      found to effectively generate clear and easy-to-interpret PFGE patterns of a
      range of probiotic strains. Some probiotic strains from different sources shared
      highly similar PFGE patterns. CONCLUSIONS: Results document the value of
      genotypic strain identification methods, combined with phenotypic methods, for
      determining probiotic strain identity and relatedness. No correlation was found
      between relatedness determined by carbohydrate fermentation profiles alone
      compared with PFGE analysis alone. Some commercial strains are probably derived
      from similar sources. SIGNIFICANCE AND IMPACT OF THE STUDY: This approach is
      valuable to the probiotic industry to develop commercial strain identification
      patterns, to provide quality control of strain manufacturing production runs, to
      track use of protected strains and to determine the relatedness among different
      research and commercial probiotic strains.

PMID- 15479428
TI  - Detection of infectious hepatitis A virus by integrated cell culture/strand
      specific reverse transcriptase-polymerase chain reaction.
AB  - AIMS: A novel integrated cell culture/strand-specific reverse transcriptase
      polymerase chain reaction (RT-PCR) assay was established for detection of
      infectious hepatitis A virus (HAV). METHODS AND RESULTS: The specificity of
      tagged RT-PCR was assessed using HAV genomic positive-strand RNA extracted from
      HAV virions as reference. Water samples artificially contaminated with infectious
      or formalin-inactivated HAV were subjected to integrated cell culture (ICC)/RT
      PCR and ICC/strand-specific RT-PCR assays respectively. The tagged RT-PCR had
      high specificity for HAV negative-strand RNA. By demonstrating the formation of
      negative-strand RNA replicative intermediate, ICC/strand-specific RT-PCR can
      distinguish between infectious and non-infectious HAV. The described method
      detected infectious HAV at inoculation level of 10(0) TCID50 per flask within 4
      days. CONCLUSIONS: The ICC/strand-specific RT-PCR is a novel, rapid, sensitive
      and reliable method for detection of infectious HAV. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Coupled with a suitable virus concentration and purification system,
      ICC/strand-specific RT-PCR will provide a novel and rapid method for detection of
      infectious HAV in clinical, environmental and food samples. This assay may be
      used as an alternative method to test the effective inactivation of inactivated
      virus vaccines. It may also be adapted to assess the efficacy of disinfection of
      HAV and enteric viruses in foods and water.

PMID- 15479430
TI  - Tumour susceptibility to innate and adaptive immunotherapy changes during tumour
      maturation.
AB  - Immunotherapy of tumours using T cells expanded in vitro has met with mixed
      clinical success suggesting that a greater understanding of tumour/T-cell
      interaction is required. We used a HPV16E7 oncoprotein-based mouse tumour model
      to study this further. In this study, we demonstrate that a HPV16E7 tumour passes
      through at least three stages of immune susceptibility over time. At the earliest
      time point, infusion of intravenous immune cells fails to control tumour growth
      although the same cells given subcutaneously at the tumour site are effective. In
      a second stage, the tumour becomes resistant to subcutaneous infusion of cells
      but is now susceptible to both adjuvant activated and HPV16E7-specific immune
      cells transferred intravenously. In the last phase, the tumour is susceptible to
      intravenous transfer of HPV16E7-specific cells, but not adjuvant-activated immune
      cells. The requirement for IFN-gamma and perforin also changes with each stage of
      tumour development. Our data suggest that effective adoptive T-cell therapy of
      tumour will need to be matched with the stage of tumour development.

PMID- 15479431
TI  - The multidrug resistance gene mdr1a influences resistance to ectromelia virus
      infection by mechanisms other than conventional immunity.
AB  - P-glycoprotein (P-gp), an ATP-dependent membrane pump encoded by mdr, plays, in
      addition to its ability to efflux toxins, a role in the resistance to pathogens.
      We employed mdr1a gene knock out (mdr1a-/-) mice and ectromelia virus (EV) to
      elucidate the role of P-gp in resistance to EV. Mdr1a-/- mice are more
      susceptible to EV infection than wild type (wt) mice, showing increased mortality
      and morbidity. Unexpectedly, virus titres in liver, and in vitro in macrophages
      and splenocytes were significantly lower in the more susceptible mdr1a-/- mice
      than wt littermates. Analysis of immunological mechanisms known to influence
      resistance to EV infection, such as NK and cytotoxic T cell responses, EV
      specific antibody and cytokine levels did not reveal significant differences
      between the two strains of mice. Only dendritic cells from mdr1a-/- mice showed
      impaired migration to the draining lymph nodes compared to wt mice. Our data show
      that P-gp plays an important role in EV infection by as yet undefined mechanisms.

PMID- 15479432
TI  - 'Proliferative' and 'synthetic' airway smooth muscle cells are overlapping
      populations.
AB  - The extension of airway smooth muscle cell (ASMC) functions, from just
      contractile, to synthetic and/or proliferative states, is an important component
      of airway remodelling and inflammation in asthma. Whereas all these functions
      have been demonstrated in ASM, currently, it is not known whether ASMC can be
      differentiated on the basis of their proliferative and synthetic functions. We
      used flow-cytometric techniques to determine, first, whether human ASMC are
      phenotypically heterogenous with regard to their secretory function, and second,
      the proliferative status of secretory cells. ASMC were induced to synthesize GM
      CSF by stimulation with IL-1beta and TNF-alpha followed by 10% human serum. Flow
      cytometric detection of intracellular GM-CSF revealed that only a proportion of
      cells in culture (approximately 20-60%) synthesize GM-CSF. To determine the
      proliferative status of GM-CSF producing cells, ASMC were pretreated with 5,6
      carboxyfluorescein diacetate succinimidyl ester (CFSE), a fluorescein based dye
      used to track cell division, prior to cytokine/serum stimulation. Simultaneous
      analysis of intracellular GM-CSF and CFSE revealed that GM-CSF producing cells
      were present in both the divided and undivided ASMC populations. Thus, cytokine
      production and proliferation occurred in overlapping ASMC populations and prior
      progression through the cell cycle was not essential for ASMC cytokine
      production.

PMID- 15479433
TI  - Interaction of soluble CD163 with activated T lymphocytes involves its
      association with non-muscle myosin heavy chain type A.
AB  - CD163 is a monocyte/macrophage-specific scavenger receptor that undergoes
      ectodomain shedding upon an inflammatory stimulus. Soluble CD163 (sCD163)
      actively inhibits lymphocyte proliferation, but to date exactly how it interacts
      with these cells has remained elusive. We screened T lymphocytes and endothelial
      cells for proteins binding to sCD163. In both cell types a high affinity binding
      protein was detected. Partial sequencing of the protein revealed sequence
      identity to a non-muscle myosin heavy chain type A. Employing labelled sCD163 we
      found little specific binding of sCD163 to the extracellular domains of T
      lymphocytes and human umbilical vein endothelial cells (HUVEC). In activated T
      lymphocytes we demonstrated specific binding of sCD163 to intracellular
      structures as well as the presence of the native protein within the cell after co
      incubation with purified sCD163. Furthermore, we developed a novel ELISA for
      highly specific detection of sCD163-myosin complexes. These complexes were
      present in activated T lymphocytes after incubation with shed sCD163. Co
      localization of sCD163 and cellular myosin in T lymphocytes was further confirmed
      by fluorescence microscopy. Our results suggest that sCD163 associates with
      cellular myosin, thereby possibly modulating the cells' response to an
      inflammatory stimulus.

PMID- 15479434
TI  - Vaccine adjuvants: current state and future trends.
AB  - The problem with pure recombinant or synthetic antigens used in modern day
      vaccines is that they are generally far less immunogenic than older style live or
      killed whole organism vaccines. This has created a major need for improved and
      more powerful adjuvants for use in these vaccines. With few exceptions, alum
      remains the sole adjuvant approved for human use in the majority of countries
      worldwide. Although alum is able to induce a good antibody (Th2) response, it has
      little capacity to stimulate cellular (Th1) immune responses which are so
      important for protection against many pathogens. In addition, alum has the
      potential to cause severe local and systemic side-effects including sterile
      abscesses, eosinophilia and myofascitis, although fortunately most of the more
      serious side-effects are relatively rare. There is also community concern
      regarding the possible role of aluminium in neurodegenerative diseases such as
      Alzheimer's disease. Consequently, there is a major unmet need for safer and more
      effective adjuvants suitable for human use. In particular, there is demand for
      safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. Other
      needs in light of new vaccine technologies are adjuvants suitable for use with
      mucosally-delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines.
      Each of these areas are highly specialized with their own unique needs in respect
      of suitable adjuvant technology. This paper reviews the state of the art in the
      adjuvant field, explores future directions of adjuvant development and finally
      examines some of the impediments and barriers to development and registration of
      new human adjuvants.

PMID- 15479435
TI  - Aluminium compounds for use in vaccines.
AB  - Aluminium adjuvants are the most widely used adjuvants in both human and
      veterinary vaccines. These adjuvants have been used in practical vaccination for
      more than 60 years and are generally recognized as safe and as stimulators of Th2
      immunity. The present review gives a short introduction to the pioneering
      research at the start of the use of aluminium compounds as adjuvants, including
      references on the chemistry of these compounds. Analytical methods for
      identifying the most commonly used aluminium compounds, such as boehmite and
      aluminium hydroxyphosphate, are mentioned. Emphasis is placed on the important
      factors for antigen adsorption and on the latest work using gene-deficient mice
      in the research of the mechanism of aluminium adjuvants in terms of cytokine and
      T-cell subset stimulation. Key references on the ability of aluminium adjuvants
      to stimulate IgE and also in vivo clearing of aluminium adjuvants are discussed.
      Furthermore, the review addresses the issue of local reactions in the context of
      injection route and local tissue disturbance. Possible new applications of
      aluminium adjuvants in, for example, combined aluminium-adsorbed protein and DNA
      oligonucleotide vaccines as well as the possible use of aluminium adjuvants in
      combination with IL-12 to stimulate Th1-type immune responses are mentioned.

PMID- 15479436
TI  - Vaccines that facilitate antigen entry into dendritic cells.
AB  - Although vaccines have been highly successful in preventing and treating many
      infectious diseases (including smallpox, polio and diphtheria) diseases prevalent
      in the developing world such as malaria and HIV, that suppress the host immune
      system, require new, multiple strategies that will be defined by our growing
      understanding of specific immune activation. The definition of adjuvants,
      previously thought of as any substance that enhanced the immunogenicity of
      antigen, could now include soluble mediators and antigenic carriers that interact
      with surface molecules present on DC (e.g. LPS, Flt3L, heat shock protein)
      particulate antigens which are taken up by mechanisms available to APC but not
      other cell types (e.g. immunostimulatory complexes, latex, polystyrene particles)
      and viral/bacterial vectors that infect antigen presenting cells (e.g. vaccinia,
      lentivirus, adenovirus). These approaches, summarized herein, have shown
      potential in vaccinating against disease in animal models, and in some cases in
      humans. Of these, particle-antigen conjugates provide rapid formulation of the
      vaccine, easy storage and wide application, with both carrier and adjuvant
      functions that activate DC. Combined vaccines of the future could use adjuvants
      such as virus-like particles and particles targeted towards a predominant
      cellular type or immune response, with target cell activation enhanced by growth
      factors or maturation signals prior to, or during immunization. Collectively,
      these new additions to adjuvant technology provide opportunities for more
      specific immune regulation than previously available.

PMID- 15479437
TI  - Increased adjuvant activity of minimal CD8 T cell peptides incorporated into
      lipid-core-peptides.
AB  - A problem facing the use of subunit peptide and protein vaccines is their
      inability to stimulate protective immune responses. Many different approaches
      have been utilized to overcome this inefficient immune activation. The approach
      we have taken is to modify the vaccine antigen so that it now has adjuvant
      properties. To do this, multiple copies of minimal CD8 T cell epitopes were
      attached to a poly lysine lipid core. These constructs are known as lipid-core
      peptides (LCP). The research presented here examines the adjuvant activity of
      LCP. Using mouse models, we were able to show that LCP were indeed able to
      activate antigen-presenting cells in vitro and to activate cytotoxic T-cell
      responses in vivo. More importantly, LCP were able to stimulate the development
      of a protective antitumour immune response.

PMID- 15479438
TI  - Immunostimulatory CpG motifs induce CTL responses to HIV type I oligomeric gp140
      envelope protein.
AB  - In the present study we investigated the immunomodulatory effects of two
      adjuvants, liposomal lipid A [L(LA)] and CpG-containing oligodeoxynucleotides
      (CpG ODN), to the HIV-1 ogp140 envelope protein. Administration of each of these
      adjuvants separately with unencapsulated ogp140 resulted in low antibody titres.
      Encapsulation of ogp140 in liposomes containing lipid A resulted in a sixfold
      increase in anti-ogp140 antibodies. The antibody titres were further enhanced
      threefold by the addition of CpG ODN. Priming and boosting BALB/c mice with
      unencapsulated ogp140 with L(LA) or encapsulation in liposomes containing lipid A
      induced a mixed Th1/Th2 type of immune response. In contrast, immunization with
      L(ogp140 + LA) plus CpG ODN switched the immune response to a Th-1 response with
      elevated anti-ogp140 IgG2a antibodies and IFN-gamma levels. Both adjuvants
      induced excellent ogp140-specific proliferative and CTL responses. Therefore, for
      the induction of high titre antibodies, but not for cellular responses, the
      antigen and lipid A have to be present in the same liposomes. These results can
      have significant implications in directing the Th1 or Th2 differentiation of
      antigen-specific immune responses in the context of vaccine development.

PMID- 15479439
TI  - Liposome-stabilized oil-in-water emulsions as adjuvants: increased emulsion
      stability promotes induction of cytotoxic T lymphocytes against an HIV envelope
      antigen.
AB  - Protective or therapeutic immunity against HIV infection is currently believed to
      require both antibody and CTL responses against the envelope protein. In the
      present study, the adjuvant activity of a unique oil-in-water emulsion, in which
      liposomes containing lipid A (LA) and encapsulated antigen served as the
      emulsifying agent, was examined in mice using oligomeric gp140 (ogp140) derived
      from the HIV-1 envelope as the antigen. Emulsions rendered either highly stable
      or unstable by altering the ratio of liposomes to oil were used to examine the
      effect of stability of the emulsion on adjuvant activity. Stable and unstable
      emulsions had similar potencies for inducing both IgG antibodies to ogp140 and
      antigen-specific T-lymphocyte proliferation. Stable emulsions, but not unstable
      emulsions, induced antigen-specific CTL responses, possibly because of the depot
      effect of the stable emulsions. Furthermore, stable emulsions induced lower
      IgG2a/IgG1 ratios than the unstable emulsions. We conclude that stable liposomal
      oil-in-water emulsions provide an effective means of obtaining both antibody and
      CTL responses against an HIV envelope antigen.

PMID- 15479440
TI  - Development of a nasal vaccine for chronic hepatitis B infection that uses the
      ability of hepatitis B core antigen to stimulate a strong Th1 response against
      hepatitis B surface antigen.
AB  - There are estimated to be 350 million chronic carriers of hepatitis B infection
      worldwide. Patients with chronic hepatitis B are at risk of liver cirrhosis with
      associated mortality because of hepatocellular carcinoma and other complications.
      An important goal, therefore, is the development of an effective therapeutic
      vaccine against chronic hepatitis B virus (HBV). A major barrier to the
      development of such a vaccine is the impaired immune response to HBV antigens
      observed in the T cells of affected patients. One strategy to overcome these
      barriers is to activate mucosal T cells through the use of nasal vaccination
      because this may overcome the systemic immune downregulation that results from
      HBV infection. In addition, it may be beneficial to present additional HBV
      epitopes beyond those contained in the traditional hepatitis B surface antigen
      (HbsAg) vaccine, for example, by using the hepatitis B core antigen (HBcAg). This
      is advantageous because HBcAg has a unique ability to act as a potent Th1
      adjuvant to HbsAg, while also serving as an immunogenic target. In this study we
      describe the effect of coadministration of HBsAg and HBcAg as part of a strategy
      to develop a more potent and effective HBV therapeutic vaccine.

PMID- 15479441
TI  - Effect of incorporation of the adjuvant Quil A on structure and immune
      stimulatory capacity of liposomes.
AB  - Liposomes have been widely used as drug delivery systems for many years. However,
      they are of limited use as delivery systems for subunit vaccines due to their low
      immunogenicity. Here we examine the effect of incorporating the adjuvant Quil A
      into liposomes on the type of particles produced, on the ability of the different
      particles to incorporate antigen and on the ability of the different particles to
      stimulate murine bone-marrow-derived dendritic cells (DC) and lymphocytes. The
      incorporation of increasing amounts of Quil A, from 20% to 70% of the total lipid
      into liposomes, reduces the size of the particles that form in aqueous dispersion
      and decreases antigen incorporation and uptake by DC. Interestingly, the
      particles with 20% Quil A were more toxic to cells in culture than the particles
      containing 70% Quil A, and the 20% particles were also more immunostimulatory.

PMID- 15479444
TI  - In vivo determination of skin surface topography using an optical 3D device.
AB  - BACKGROUND/PURPOSE: Topography of the skin surface is a mirror of the functional
      skin status. Therefore, its evaluation is of great interest for dermatological
      research. In the present study, a new optical measuring system was applied to
      evaluate human skin surface topography in vivo and non-invasively, in order to
      determine elastotic and mimic wrinkles dependent on age, body site and therapy.
      METHODS: The measurements were performed on the back (n=5), the flexor forearm
      (n=14) of volunteers in different age groups and on the face of women (n=4)
      participating in an anti-wrinkle study. The evaluation of the three-dimensional
      profiles was performed determining skin surface parameters (mean roughness
      (R(a)), mean depth of roughness (R(z)), maximum roughness (R(m)) and waviness
      (W(t))) and applying Fourier analysis. RESULTS: Significant increases in all
      surface parameters were obtained on the forearms with increasing age. Differences
      between the surface topographies of forearm and back were only expressed by the
      waviness and the Fourier analysis. The treatment with botulinum Toxin A led to a
      diminution of mimic wrinkles as reflected by the furrow profiles. CONCLUSIONS:
      The results show a significant dependence of the skin surface topography on the
      age of the volunteer and the body site measured. Particularly the waviness, the
      Fourier analysis and the furrow profiles reflect such dependencies. The system
      used also fulfils the requirements for the testing of therapies, as was
      demonstrated by the reduction of mimic wrinkles after treatment with botulinum
      Toxin A.

PMID- 15479445
TI  - Enhancement of lesion classification using divergence, curl and curvature of skin
      pattern.
AB  - BACKGROUND/PURPOSE: The observation that skin pattern tends to be disrupted by
      malignant but not by benign skin lesions suggests that measurements of skin
      pattern disruption on simply captured white light optical clinical (WLC) skin
      images could be a useful contribution to a diagnostic feature set. Previous work
      which generated a flow field of skin pattern using a measurement of local line
      direction and variation determined by the minimum eigenvalue and its
      corresponding eigenvector of the local tensor matrix to measure skin pattern
      disruption was computationally low cost and encouraging. This paper explores the
      possibility of extracting new features from the first and second differentiations
      of this flow field to enhance classification performance. METHODS: The skin
      pattern was extracted from WLC skin images by high-pass filtering. The skin line
      direction was estimated using a local image gradient matrix to produce a flow
      field of skin pattern. Divergence, curl, mean and Gaussian curvatures of this
      flow field were computed from the first and second differentiations of this flow
      field. The difference of these measures combined with skin line direction across
      the lesion image boundary was used as a lesion classifier. RESULTS: A set of
      images of malignant melanoma and benign naevi were analysed as above and the
      scatter plot in a two-dimensional dominant feature space using principal
      component analysis showed excellent separation of benign and malignant lesions. A
      receiver operating characteristic plot enclosed an area of 0.96. CONCLUSIONS: The
      experimental results show that the divergence, curl, mean and Gaussian curvatures
      of the flow field can increase lesion classifier accuracy. Combined with skin
      line direction they are promising features for distinguishing malignant melanoma
      from benign lesions and the methods used are computationally efficient which is
      important if their use is to be considered in clinical practice.

PMID- 15479446
TI  - Influence of hydration and experimental length scale on the mechanical response
      of human skin in vivo, using optical coherence tomography.
AB  - BACKGROUNDS/AIMS: Human skin is a complex tissue consisting of different layers.
      To gain better insight into the mechanical behaviour of different skin layers,
      the mechanical response was studied with experiments of various length scales.
      Also, the influence of (superficial) hydration on the mechanical response is
      studied. The work is based on the hypothesis that experiments with different
      length scales represent the mechanical behaviour of different skin layers. For
      suction, this means that a large aperture diameter reflects the behaviour of
      mainly dermis, whereas a very small diameter reflects the behaviour of only the
      top layer of the skin. METHODS: Suction measurements at varying pressures and
      aperture sizes were performed on the volar forearm of 13 subjects aged 29-47
      years. The deformation of the skin was visualized using ultrasound (US) (dermis)
      and optical coherence tomography (OCT) (epidermis and dermis). US measurements
      were performed on hydrated skin, OCT measurements on dry and hydrated skin. The
      experiment was simulated by a finite element model (FEM) exhibiting extended
      Mooney material behaviour. An identification method was used to compare the
      experimental and numerical results to identify the parameters of the material.
      RESULTS: The material parameters C(10) and C(11) were calculated for four
      subjects: C(10)=29.6+/-21.1 kPa and C(11)=493+/-613 kPa for 6 mm aperture
      diameter, C(10)=11.5+/-8.7 kPa and C(11)=18.3+/-12.6 kPa for 2 mm aperture
      diameter and C(10)=10.8+/-9.5 kPa and C(11)=9.3+/-7.7 kPa for 1 mm aperture
      diameter. Skin hydration caused ambiguous effects on the mechanical response.
      CONCLUSIONS: US and OCT, combined with suction, using varying apertures sizes,
      proved to be a valuable tool to study the mechanical behaviour of different skin
      layers. With increasing experimental length scale, increasing values for the
      parameters of the material model were found. This indicates the need of a multi
      layered material layer FEM, which can be used to identify mechanical behaviour of
      epidermis and dermis.

PMID- 15479447
TI  - A cure for traffic jams: small molecule chaperones in the endoplasmic reticulum.
AB  - Folding in the endoplasmic reticulum is the limiting step for the biogenesis of
      most secretory pathway cargo proteins; proteins which fail to fold are initially
      retained in the endoplasmic reticulum and subsequently often degraded. Mutations
      that affect secretory protein folding have profound phenotypes irrespective of
      their direct impact on protein function, because they prevent secretory proteins
      from reaching their final destination. When unicellular organisms are stressed by
      fluctuation of temperature or ionic strength, they synthesize high concentrations
      of small molecules such as trehalose or glycerol to prevent protein denaturation.
      These osmolytes can also stabilize mutant secretory proteins and allow them to
      pass secretory protein quality control in the endoplasmic reticulum. Specific
      ligands and cofactors such as ions, sugars, or peptides have similar effects on
      specific defective proteins and are beginning to be used as therapeutic agents
      for protein trafficking diseases.

PMID- 15479448
TI  - Pharmacologic rescue of conformationally-defective proteins: implications for the
      treatment of human disease.
AB  - The process of quality control in the endoplasmic reticulum involves a variety of
      mechanisms which ensure that only correctly folded proteins enter the secretory
      pathway. Among these are conformation-screening mechanisms performed by molecular
      chaperones that assist in protein folding and prevent non-native (or misfolded)
      proteins from interacting with other misfolded proteins. Chaperones play a
      central role in the triage of newly formed proteins prior to their entry into the
      secretion, retention, and degradation pathways. Despite this stringent quality
      control mechanism, gain- or loss-of-function mutations that affect protein
      folding in the endoplasmic reticulum can manifest themselves as profound effects
      on the health of an organism. Understanding the molecular, cellular, and
      energetic mechanisms of protein routing could prevent or correct the structural
      abnormalities associated with disease-causing misfolded proteins. Rescue of
      misfolded, "trafficking-defective", but otherwise functional, proteins is
      achieved by a variety of physical, chemical, genetic, and pharmacological
      approaches. Pharmacologic chaperones (or "pharmacoperones") are template
      molecules that may potentially arrest or reverse diseases by inducing mutant
      proteins to adopt native-type-like conformations instead of improperly folded
      ones. Such restructuring leads to a normal pattern of cellular localization and
      function. This review focuses on protein misfolding and misrouting related to
      various disease states and describes promising approaches to overcoming such
      defects. Special attention is paid to the gonadotropin-releasing hormone
      receptor, since there is a great deal of information about this receptor, which
      has recently emerged as a particularly instructive model.

PMID- 15479449
TI  - Association of Cdc42/N-WASP/Arp2/3 signaling pathway with Golgi membranes.
AB  - Recent findings indicate that Cdc42 regulates Golgi-to-ER (endoplasmic reticulum)
      protein transport through N-WASP and Arp2/3 (Luna et al. 2002, Mol. Biol. Cell,
      13:866-879). To analyse the components of the Cdc42-governed signaling pathway in
      the secretory pathway, we localized Cdc42, N-WASP and Arp2/3 in the Golgi complex
      by cryoimmunoelectron microscopy. Cdc42 is found throughout the Golgi stack,
      particularly in cis/middle cisternae, whereas N-WASP and Arp3 (a component of the
      Arp2/3 complex) are restricted to cis cisternae. Arp3 also colocalized in peri
      Golgi tubulovesicular structures with either KDEL receptor or GM130. Even though
      Arp3 is not found in TGN46-positive cisternal elements, a small fraction of Arp3
      labeled tubulo-vesicular elements showed TGN46 labeling. Active Cdc42 (GTP-bound
      form) induced relocation of N-WASP and Arp3 to the lateral rims of Golgi
      cisternae. These results show that the actin nucleation and polymerization
      signaling pathway governed by Cdc42/N-WASP/Arp operates in the Golgi complex of
      mammalian cells, further implicating actin dynamics in Golgi-associated membrane
      trafficking.

PMID- 15479450
TI  - Multiple nuclear localization sequences allow modulation of 5-lipoxygenase
      nuclear import.
AB  - The nuclear import of proteins typically requires the presence of a nuclear
      localization sequence (NLS). Some proteins have more than one NLS, but the
      significance of having multiple NLSs is unclear. The enzyme 5-lipoxygenase (5-LO)
      has three NLSs that, unlike the tight cluster of basic residues of the classical
      SV40 large T antigen NLS, contain dispersed basic residues. When attached to
      green fluorescent protein (GFP), individual 5-LO NLSs caused quantitatively and
      statistically less import than the SV40 NLS. Combined 5-LO NLSs produced nuclear
      import that was comparable to that of the SV40 NLS. As expected, GFP/NLS proteins
      displayed relatively uniform import in all cells. However, a fusion protein of
      GFP plus the 5-LO protein, modified to contain only one functional NLS, produced
      some cells with import and some cells without import. A GFP/5-LO fusion protein
      containing two functional NLSs produced four identifiable levels of nuclear
      import. Quantitative and visual analysis of a population of cells expressing the
      intact GFP/5-LO protein, with three intact NLSs, indicated five levels of nuclear
      import. This suggested that the subcellular distribution of 5-LO may vary widely
      in normal cells of the body. Consistent with this, immunohistochemical staining
      of lung sections found that individual macrophages, in situ, displayed cell
      specific levels of import of 5-LO. Since nuclear accumulation is known to affect
      5-LO activity, multiple NLSs may allow graded regulation of activity via
      controlled import. Multiple NLSs on other proteins may likewise allow fine
      control of protein action through modulation of the level of import.

PMID- 15479451
TI  - Molecular partitioning during host cell penetration by Toxoplasma gondii.
AB  - During invasion by Toxoplasma gondii, host cell transmembrane proteins are
      excluded from the forming parasitophorous vacuole membrane (PVM) by the tight
      apposition of host and parasite cellular membranes. Previous studies suggested
      that the basis for the selective partitioning of membrane constituents may be a
      preference for membrane microdomains, and this hypothesis was herein tested. The
      partitioning of a diverse group of molecular reporters for raft and nonraft
      membrane subdomains was monitored during parasite invasion by time-lapse video or
      confocal microscopy. Unexpectedly, both raft and nonraft lipid probes, as well as
      both raft and nonraft cytosolic leaflet proteins, flowed unhindered past the host
      parasite junction into the PVM. Moreover, neither a raft-associated type 1
      transmembrane protein nor its raft-dissociated counterpart accessed the PVM,
      while a multispanning membrane raft protein readily did so. Considered together
      with previous data, these studies demonstrate that selective partitioning at the
      host-parasite interface is a highly complex process, in which raft association
      favors, but is neither necessary nor sufficient for, inclusion into the T. gondii
      PVM.

PMID- 15479452
TI  - LdARF1 in trafficking and structural maintenance of the trans-Golgi cisternal
      network in the protozoan pathogen Leishmania donovani.
AB  - Adenosine diphosphate ribosylation factors (ARFs) are small guanosine-5'
      triphosphatases that are essential in vesicular trafficking and in the
      maintenance of the Golgi network. In this report, we identified a homolog of the
      mammalian ARF1 in the human pathogenic protozoan parasite, Leishmania donovani
      (Ld). Ld ARF1 is a 549 bp gene encoding a 183-amino acid deduced protein of
      approximately 20 kDa. We demonstrated by Southern blot analysis that there are at
      least two copies of ARF1 in the Ld genome. Moreover, Northern blot analysis
      revealed that Ld ARF1 is expressed on a 1.35 kb transcript in both the insect
      vector (promastigotes) and mammalian host (amastigotes) forms of this parasite.
      Fluorescent microscopy studies using Ld promastigotes episomally transfected with
      an ARF1::GFP (green fluorescent protein) chimeric construct showed that such
      chimeras appeared to localize to the Golgi region of these organisms. This
      observation was verified by immunoelectron microscopy using an anti-GFP antibody.
      Such studies also revealed that Ld ARF1::GFP chimeras localized to trans-Golgi
      vesicles, the flagellar pocket/reservoir and other vesicles located between the
      trans-Golgi network and flagellar pocket in these apically polarized cells.
      Fluorescence recovery after photobleaching and fluorescence loss in
      photobleaching experiments revealed both the dynamic binding and releasing
      activity of Ld ARF1 from the Golgi network in these parasites. Further, episomal
      expression of a constitutively active ("on") ARF1 (Q71L mutation) resulted in the
      aberrant swelling and distended-structure of the trans-Golgi cisternae in these
      cells. These results show that Ld ARF1 is transiently associated with the Golgi
      network and plays a role in the structural maintenance of this organelle in these
      important human pathogens.

PMID- 15479453
TI  - Unexpected intracellular localization of the AMD-associated cystatin C variant.
AB  - Cystatin C is abundantly expressed by the retinal pigment epithelium (RPE) of the
      eye. Targeting of cystatin C to the Golgi apparatus and processing through the
      secretory pathway of RPE cells are dependent upon a 26-amino acid signal sequence
      of precursor cystatin C. A variant with an alanine (A) to threonine (T) mutation
      in the penultimate amino acid of the signal sequence (A25T) was recently
      correlated with increased risk of developing exudative age-related macular
      degeneration. The biochemical consequence of the A25T mutation upon targeting of
      the protein is reported here. Targeting and trafficking of full-length mutant
      (A25T) precursor cystatin C-enhanced green fluorescent protein fusion protein
      were studied in living, cultured retinal pigment epithelial and HeLa cells.
      Confocal microscopy studies were substantiated by immunodetection. In striking
      contrast to wild-type precursor cystatin C fusion protein conspicuously targeted
      to the Golgi apparatus, the threonine variant was associated principally with
      mitochondria. Some diffuse fluorescence was also observed throughout the
      cytoplasm and nucleus (but not nucleoli). Secretion of fusion protein derived
      from the threonine variant was reduced by approximately 50% compared with that of
      the wild-type cystatin C fusion protein. Expression of the variant fusion protein
      did not appear to impair expression or secretion of endogenous cystatin C.

PMID- 15479454
TI  - Exosome secretion: the art of reutilizing nonrecycled proteins?
AB  - Multivesicular bodies contain membrane vesicles which either undergo lysosomal
      digestion or are released in the extracellular environment as exosomes. Evidence
      is accumulating that supports a physiological role for exosomes in, for example,
      antigen presentation or removal of transferrin receptor during reticulocyte
      development. Here, inspired by observations on exosomal release from
      reticulocytes, we discuss the potential involvement of the so-called ESCRT
      mechanism in the entrapment of both lysosomal and exosomal cargo within the
      intralumenal vesicles of multivesicular bodies. We propose that this mechanism
      operates at different sites in the endocytic itinerary in different cells,
      thereby providing a tool for directional sorting. We also explore the possibility
      that the efficiency of sorting of molecules into exosomes increases when the
      recycling kinetics of molecules decreases, exosomal sorting being favored by
      intermolecular interactions occurring within lipid domains, or with protein webs,
      that slow lateral mobility. These considerations are mirrored in the context of
      current knowledge on the mechanism of protein sorting for degradation in
      lysosomes, and the hijacking of such mechanisms by some retroviruses for particle
      budding.

PMID- 15479457
TI  - Herpesvirus infections in xenotransplantation: pathogenesis and approaches.
AB  - Infectious risk remains an important consideration in the clinical application of
      xenotransplantation. Vascularized xenografts create unique immunological niches
      in which bidirectional transmission of pathogens between donor and recipient may
      occur. Enhanced replication of many pathogens is stimulated by the immune
      responses induced by transplantation and by the immune suppression used to
      prevent graft rejection. Herpesviruses are the prototype viruses that are
      activated during immunosuppression. Quantitative diagnostic molecular assays have
      been developed for the known herpesviruses causing infection in pigs. Recent data
      suggest that some herpesviral infections, such as porcine cytomegalovirus, may be
      excluded from swine used as source animals by careful breeding, while others will
      require novel strategies for control. This review focuses on porcine and baboon
      herpesviruses in pig-to-non-human primate solid organ xenotransplantation
      including direct effects (tissue damage), indirect effects (coagulopathy,
      rejection), and possible approaches to these infections.

PMID- 15479458
TI  - Use of porcine tumor necrosis factor receptor 1-Ig fusion protein to prolong
      xenograft survival.
AB  - BACKGROUND: Delayed rejection of xenografts is a major hurdle that needs to be
      addressed to achieve long-term engraftment in the pig-to-primate transplant
      setting. Both vascular and avascular xenografts are susceptible to a delayed
      rejection process that comprises humoral and cellular responses. Tumor necrosis
      factor (TNF) is believed to play a role in this process by promoting cell
      activation, apoptosis and the recruitment of inflammatory cells. To address this
      problem, we engineered the donor cell in such a way that it could block both
      human and porcine TNF. METHODS: We produced a recombinant fusion protein
      containing the extracellular domain of the porcine TNF-Receptor 1 and an IgG Fc
      moiety (pTNFR1Ig). We first evaluated by flow cytometry the pTNFR1Ig capacity to
      prevent TNF alpha-induced expression of SLAI, SLAII, VCAM-1, ICAM-1 and E
      selectin on the cell surface of porcine aortic endothelial cells (PAEC). The
      effect on TNF alpha-mediated cell death was also assessed by propidium iodide
      staining after incubating PAEC with TNF alpha plus cycloheximide for 24 h. PAEC
      and porcine fibroblasts were subsequently engineered by retroviral infection to
      express and secrete pTNFR1Ig and their resistance to the TNF alpha effects was
      tested in vitro. Finally, we transplanted mock-control and pTNFR1Ig-expressing
      PAEC under the kidney capsule of BALB/c mice in the absence of immunosuppression
      and examined the degree of rejection at 2 and 3 weeks post-transplantation.
      RESULTS: Treatment with pTNFR1Ig resulted in a very potent blockade of human,
      porcine and murine TNF alpha activity on porcine cells. It inhibited the
      upregulation of all cell surface markers of activation tested as well as the TNF
      alpha-mediated cell death. Moreover, pTNFR1Ig-expressing PAEC showed prolonged
      engraftment in a pig-to-mouse xenotransplant model. CONCLUSIONS: Incorporation of
      strategies that block TNF may prove useful in the development of xenografts
      resistant to delayed rejection.

PMID- 15479459
TI  - Molecular investigation of hepatitis E virus infection in domestic and miniature
      pigs used for medical experiments.
AB  - BACKGROUND: Hepatitis E virus (HEV) infection is highly prevalent among domestic
      pigs in Japan. It has been reported that pig handlers such as farmers and
      veterinarians are at increased risk of contracting HEV infection. Pigs are
      regarded as the most acceptable candidate animals for xenotransplantation and,
      recently, they are being used as experimental animals. METHODS: We investigated
      the prevalence of IgG class antibodies to swine HEV (anti-HEV) and HEV RNA among
      152 2-month-old domestic pigs and 38 miniature pigs of 4 to 10 months of age that
      had been brought to our center for medical experiments from five swine farms (A
      E) in Japan. Serum samples were tested for anti-HEV by in-house enzyme
      immunoassay, and for HEV RNA by reverse transcription-polymerase chain reaction
      using primers targeting the open reading frame 2 (ORF2) region. RESULTS: One
      percent (one of 84), 6% (one of 16), and 38% (20 of 52) of the domestic pigs from
      farms A, B and C, respectively, had detectable HEV RNA, and the 22 HEV isolates
      recovered from the viremic pigs were 89.8 to 100% identical to each other in the
      412-nucleotide sequence of ORF2 and segregated into three clusters within
      genotype 3. Although one pig from farm A had detectable HEV RNA reproducibly, the
      HEV isolate recovered from this pig was up to 100% similar to those recovered
      from pigs from farm C, and the sera from all 84 pigs from farm A were negative
      for anti-HEV. These results suggested that farm A is free from HEV infection. As
      the viremic pig from farm A had been raised for 1 month in a barn at our center
      before serum sampling, it is most likely that the pig acquired HEV infection in
      the barn at our center where HEV-viremic pigs from farm C had been reared for
      several days approximately 3 months earlier. The 38 miniature pigs from farms D
      and E were negative for both anti-HEV and HEV RNA. In an attempt to further
      investigate the prevalence of HEV infection, pigs that were being raised in four
      swine farms (farms A, C, D, and E) were tested for anti-HEV. Although 96 (86%) of
      the 112 pigs from farm C were positive for anti-HEV, none of the 48 pigs in farm
      A and 138 miniature pigs in farms D and E was positive for anti-HEV. CONCLUSIONS:
      These results suggest that three of the five swine farms tested were free from
      HEV, and that periodic testing for anti-HEV and HEV RNA of pigs used as
      experimental animals and pigs raised in swine farms from which pigs are
      purchased, is useful for providing HEV-free pigs to researchers who are engaged
      in studies using pigs.

PMID- 15479460
TI  - Reference values for clinical chemistry and clinical hematology parameters in
      baboons.
AB  - BACKGROUND: In vivo xenotransplantation modeling in large animal species is often
      performed in nonhuman primates, including baboons. For proper data
      interpretation, reference values for clinical chemistry and hematology are
      required. METHODS: These values are available from baseline levels in animals
      subjected to tolerability/pharmacokinetic studies. For each individual study two
      tests for clinical chemistry and hematology were performed before the start of
      treatment. RESULTS AND CONCLUSION: We present such data from 17 male and 16
      female baboons, with body weights ranging between 4.4 and 14.0 kg (males) and 4.1
      and 15.0 kg (females), respectively. The number of duplicate samples per animal
      determined before each individual study ranged between one and five. These data
      are reported here to provide baseline values for veterinarians and investigators
      using baboons in experimental studies, particularly in xenotransplantation.

PMID- 15479461
TI  - Hyperacute rejection of hDAF-transgenic pig organ xenografts in cynomolgus
      monkeys: influence of pre-existing anti-pig antibodies and prevention by the
      alpha GAL glycoconjugate GAS914.
AB  - BACKGROUND: Our introductory pig-to-cynomolgus monkey heart or kidney
      transplantation using organs from pigs transgenic for human decay-accelerating
      factor (hDAF), showed a high incidence of hyperacute rejection (HAR), which was
      ascribed to extraordinary high levels of anti-pig antibodies. We evaluated the
      efficacy of GAS914, a Gal alpha 1-3Gal trisaccharide linked to a poly-l-lysine
      backbone, in inhibition of HAR. METHODS: hDAF transgenic heterotopic heart (n =
      15) or life-supporting kidney (n = 8) transplantation included induction with
      cyclophosphamide or anti-thymocyte globulin, and maintenance with cyclosporine or
      tacrolimus, steroids and mycophenolate sodium/mofetil. Four doses of GAS914 were
      given before transplantation. Rejection was confirmed by graft histology, and
      anti-pig antibody levels were determined in various assays. RESULTS: Four of six
      heart transplants without GAS914 treatment showed HAR. Nine subsequent
      transplants with GAS914 pre-treatment, did not show HAR (chi-square, P < 0.05).
      Two of four kidney transplants without GAS914 treatment ended with HAR. Four
      subsequent transplants with GAS914 did not show HAR. Animals with HAR showed
      extremely high antibody levels. Samples just before transplantation showed
      significantly higher antibody levels in recipients presenting with HAR. In all
      assays antibody levels were significantly lowered by GAS914 pre-treatment.
      CONCLUSIONS: HAR of hDAF solid organs could be ascribed to high levels of anti
      pig antibodies. It is hypothesized that the hDAF transgene shows a threshold in
      efficacy, above which an overwhelming attack by antibodies and complement
      activation cannot be modulated to prevent HAR. HAR does not occur when animals
      with lower levels are used, or when antibodies are effectively depleted from the
      circulation by GAS914 treatment.

PMID- 15479462
TI  - Prolonged survival of fetal pig islet xenografts in mice lacking the capacity for
      an indirect response.
AB  - BACKGROUND: Xenografts of islets from organ-cultured fetal pig pancreases
      transplanted into non-immunosuppressed mice are rejected within 10 days.
      Immunosuppression with anti-T cell (anti-CD4) monoclonal antibody alone delays
      rejection of these xenografts for about 28 days, but rejection eventually occurs
      despite marked depletion of T cells. To determine if the critical CD4+ T cells
      responsible for xenograft islet rejection function through the direct or indirect
      pathway, selective class II-deficient mice that express class II antigens only on
      their thymic epithelium (not on peripheral cells) with normal numbers of CD4+ T
      cells, (class II-, CD4+), were used as recipients of xenograft islets to test if
      rejection occurs in the absence of an indirect response. METHODS: Control
      (C57BL/6) or class II-, CD4+ mice were transplanted under the kidney capsule with
      cultured fetal pig islets. Class II-, CD4+ mice have normal numbers of B cells,
      CD4+, gamma delta T cells, and slightly increased numbers of CD8+ T cells.
      Additional mice were thymectomized before receiving anti-CD4 or anti-CD8
      monoclonal antibodies. Islet graft survival was determined histologically as
      fetal pig islets were too immature to secrete insulin. RESULTS: Xenograft
      survival in control animals was 7 to 14 days. In contrast, graft survival in
      class II-, CD4+ mice was significantly prolonged to greater than 35 days.
      Depletion of CD8+ T cells in class II-, CD4+ mice prolonged graft survival to
      about 70 days. Depletion of CD4+ T cells from these mice further prolonged
      xenograft survival to about 100 days. CONCLUSIONS: These results suggest that the
      rejection of pig islets by mice initially depends on a CD4 dependent indirect
      response. The CD4 direct response also contributes to graft destruction. CD8+ T
      cells also participate in graft destruction, albeit weakly.

PMID- 15479463
TI  - Anti-non-Gal porcine endothelial cell antibodies in acute humoral xenograft
      rejection of hDAF-transgenic porcine hearts in cynomolgus monkeys.
AB  - BACKGROUND: Anti-Gal alpha 1-3Gal (Gal) antibodies play a major role in
      hyperacute rejection and acute humoral xenograft rejection (AHXR) in porcine-to
      nonhuman primate transplantation. The role of anti-non-Gal antibodies in AHXR is
      less well defined. METHODS: Eleven cynomolgus monkeys received a heterotopic
      heart transplant from a human decay-accelerating factor transgenic pig, and
      maintenance immunosuppression with cyclosporin A or tacrolimus, steroids,
      mycophenolate sodium or mycophenolate mofetil, and in 10 animals the Gal
      containing soluble glycoconjugate GAS914. Six ended with AHXR (6 to 78 day
      survival) and five did not show AHXR (9 to 36 day survival). Anti-Gal antibodies
      were depleted in vivo with GAS914, or in vitro with Gal-coated Sepharose beads.
      IgM- and IgG-class anti-non-Gal antibodies in serum depleted of anti-Gal
      antibodies were measured by flow cytometry using porcine endothelial target
      cells. RESULTS: Compared with pre-transplant values, all six recipients with AHXR
      showed a substantially higher level of anti-non-Gal IgM antibodies at rejection;
      in five animals there was also an increase in IgG-class antibodies. There was no
      relevant change in recipients without AHXR. AHXR at time of cessation of heart
      contraction could be preceeded by a steady increase in antibody level starting 2
      to 3 weeks earlier. CONCLUSIONS: AHXR is invariably associated with increased
      circulating anti-non-Gal antibodies. These antibodies are not observed in
      recipients without AHXR, and five of six recipients with AHXR were adequately
      depleted of anti-Gal antibodies by maintenance GAS914. This indicates that anti
      non-Gal antibodies play a significant role in the pathogenesis of AHXR. Also, the
      assessment of these antibodies could be used as an early monitor of AHXR.

PMID- 15479464
TI  - Prevalent human coxsackie B-5 virus infects porcine islet cells primarily using
      the coxsackie-adenovirus receptor.
AB  - BACKGROUND: We have previously demonstrated that transplanting porcine
      encephalomyocarditis virus (EMCV)-infected porcine islet cells (PICs) results in
      transmission of the virus to recipient mice, which is manifested by acute fatal
      infection within 5 to 8 days. Here, we determined PIC susceptibility to a related
      and highly prevalent human picornavirus, coxsackie B-5 virus (CVB-5). METHODS:
      PICs were inoculated with CVB-5 in vitro for up to 96 hours and infectivity,
      level of virus replication, and cellular function determined. Subsequently,
      monoclonal and polyclonal antibody blocking experiments were used to investigate
      the receptor CVB-5 uses to enter PICs, and the ability of CVB-5-infected islets
      to reverse diabetes analyzed in mice. RESULTS: Adult pig islets inoculated with
      CVB-5 in vitro showed a typical picornaviral replication cycle with a 2-h lag
      phase followed by a 4-h exponential phase during which the virus titer increased
      by 4 logs. However, CVB-5 was less cytolytic to PICs than EMCV, resulting in a
      persistent productive infection lasting for up to 96 h, with minimal evidence of
      cell lysis. Double immunostaining confirmed the presence of CVB-5 antigens in
      insulin-producing islets. Infection of PICs in the presence of antibodies against
      human coxsackie-adenovirus receptor (CAR) resulted in near complete blockage in
      production of infectious virus particles whereas blocking with anti-porcine decay
      accelerating factor (DAF, also called CD55) or anti-porcine membrane cofactor
      protein (MCP, also called CD46) only slightly decreased the number of infectious
      CVB-5 particles produced. Immunofluoresence staining showed CAR and MCP
      expression on the islet surface, but not DAF. Transplanting CVB-5-infected PICs
      into diabetic C57BL/6 mice resulted in reversal of diabetes. CONCLUSION: Although
      PICs are susceptible to human CVB-5, the infection does not appear to affect
      xenograft function in vitro or in vivo in the short term.

PMID- 15479465
TI  - Assessing the risk potential of porcine circoviruses for xenotransplantation:
      consensus primer-PCR-based search for a human circovirus.
AB  - BACKGROUND: An important issue with respect to virus safety in
      xenotransplantation is the search for human analogues of porcine viruses, because
      transmission of a porcine virus followed by recombination with a related human
      virus may lead to a new emerging virus of unknown pathogenicity, host range and
      virulence. In case of circoviruses, two types of porcine circovirus (PCV1 and
      PCV2) are described, but the existence of an analogous human circovirus has not
      yet been investigated. METHODS: This study describes the analysis of human
      samples with a consensus primer-PCR approach designed to amplify conserved
      regions from the rep gene of circoviruses from the genus Circovirus. DNA from
      human sera, lymph nodes, blood and urine was extracted and investigated with this
      method that has led previously to the identification of a new avian circovirus.
      RESULTS: By screening 1101 samples (there of 168 from immunocompromised
      patients), no evidence for the existence of a human circovirus related to the
      genus Circovirus was obtained. CONCLUSIONS: This result renders the existence of
      a human circovirus related to the porcine circoviruses more unlikely,
      nevertheless the presence of such a virus cannot be ruled out.

PMID- 15479466
TI  - Public opinion surveys about xenotransplantation.
AB  - BACKGROUND: Xenotransplantation may eventually provide a solution to the
      worldwide shortage of human organs for transplantation. Xenotransplantation is
      surrounded by profound ethical issues, both for the potential recipients and for
      the society as a whole. Concurrent with increased scientific interest, there has
      been an increasing number of quantitative public opinion surveys conducted about
      xenotransplantation in the last decade. The aim of the present study was to
      elucidate these surveys, and to assess some factors that may affect the outcome
      of them. MATERIALS AND METHODS: Surveys were identified by web and literature
      searches using key words in Medline and ISI Web of Knowledge. Reference lists of
      identified surveys were checked. Data was obtained from Inter-University
      Consortium for Political and Social Research (ICPSR) and directly from authors
      whose data were presented in another way than percentages. In total, the present
      material covered surveys from 35 sources, including 23 countries. RESULTS AND
      DISCUSSION: Results showed that almost half of the respondents accept
      xenotransplantation, whereas the remaining half did either not accept or did not
      have/state an opinion. Over time, the proportions of acceptance seemed unchanged.
      The proportion of those who did not accept decreased and the remaining proportion
      increased. This pattern was evident in Europe and the US, but not in Japan.
      Gender and education were found to be associated with opinions to
      xenotransplantation. The influence of religion was not as straightforward. This
      may partly depend on how religiosity was measured in the polls. Wording of items
      influenced levels of acceptance. If a xenotransplant was the ''only choice''
      proportions of acceptance increased, and if a ''risk for zoonotic diseases'' was
      stated proportions of acceptance decreased. When wording of survey items was
      somewhat comparable, there were often, but not always, minor differences in
      proportions of acceptance between surveys from different sources. Trends in
      opinions are best measured by the use of the same items. It is however difficult
      to phrase items that will not be affected by external events.

PMID- 15479467
TI  - Xenotransplantation literature update July-August, 2004.

PMID- 15479471
TI  - Prospective study of clinician-entered research data in the Emergency Department
      using an Internet-based system after the HIPAA Privacy Rule.
AB  - BACKGROUND: Design and test the reliability of a web-based system for
      multicenter, real-time collection of data in the emergency department (ED), under
      waiver of authorization, in compliance with HIPAA. METHODS: This was a phase I,
      two-hospital study of patients undergoing evaluation for possible pulmonary
      embolism. Data were collected by on-duty clinicians on an HTML data collection
      form (prospective e-form), populated using either a personal digital assistant
      (PDA) or personal computer (PC). Data forms were uploaded to a central, offsite
      server using secure socket protocol transfer. Each form was assigned a unique
      identifier, and all PHI data were encrypted, but were password-accessible by
      authorized research personnel to complete a follow-up e-form. RESULTS: From April
      15, 2003-April 15 2004, 1022 prospective e-forms and 605 follow-up e-forms were
      uploaded. Complexities of PDA use compelled clinicians to use PCs in the ED for
      data entry for most forms. No data were lost and server log query revealed no
      unauthorized entry. Prospectively obtained PHI data, encrypted upon server
      upload, were successfully decrypted using password-protected access to allow
      follow-up without difficulty in 605 cases. Non-PHI data from prospective and
      follow-up forms were available to the study investigators via standard file
      transfer protocol. CONCLUSIONS: Data can be accurately collected from on-duty
      clinicians in the ED using real-time, PC-Internet data entry in compliance with
      the Privacy Rule. Deidentification-reidentification of PHI was successfully
      accomplished by a password-protected encryption-deencryption mechanism to permit
      follow-up by approved research personnel.

PMID- 15479470
TI  - Protein kinases of the human malaria parasite Plasmodium falciparum: the kinome
      of a divergent eukaryote.
AB  - BACKGROUND: Malaria, caused by the parasitic protist Plasmodium falciparum,
      represents a major public health problem in the developing world. The P.
      falciparum genome has been sequenced, which provides new opportunities for the
      identification of novel drug targets. Eukaryotic protein kinases (ePKs) form a
      large family of enzymes with crucial roles in most cellular processes; hence
      malarial ePKS represent potential drug targets. We report an exhaustive analysis
      of the P. falciparum genomic database (PlasmoDB) aimed at identifying and
      classifying all ePKs in this organism. RESULTS: Using a variety of bioinformatics
      tools, we identified 65 malarial ePK sequences and constructed a phylogenetic
      tree to position these sequences relative to the seven established ePK groups.
      Predominant features of the tree were: (i) that several malarial sequences did
      not cluster within any of the known ePK groups; (ii) that the CMGC group, whose
      members are usually involved in the control of cell proliferation, had the
      highest number of malarial ePKs; and (iii) that no malarial ePK clustered with
      the tyrosine kinase (TyrK) or STE groups, pointing to the absence of three
      component MAPK modules in the parasite. A novel family of 20 ePK-related
      sequences was identified and called FIKK, on the basis of a conserved amino acid
      motif. The FIKK family seems restricted to Apicomplexa, with 20 members in P.
      falciparum and just one member in some other Apicomplexan species. CONCLUSION:
      The considerable phylogenetic distance between Apicomplexa and other Eukaryotes
      is reflected by profound divergences between the kinome of malaria parasites and
      that of yeast or mammalian cells.

PMID- 15479472
TI  - Long-term patterns in European brown hare population dynamics in Denmark: effects
      of agriculture, predation and climate.
AB  - BACKGROUND: In Denmark and many other European countries, harvest records suggest
      a marked decline in European brown hare numbers, a decline often attributed to
      the agricultural practice. In the present study, we analyse the association
      between agricultural land-use, predator abundance and winter severity on the
      number of European brown hares harvested in Denmark in the years 1955 through
      2000. RESULTS: Winter cereals had a significant negative association with
      European brown hare numbers. In contrast to this, root crop area was positively
      related to their numbers. Remaining crop categories were not significantly
      associated with the European brown hare numbers, though grass out of rotation
      tended to be positively related. The areas of root crop production and of grass
      out of rotation have been reduced by approximately 80% and 50%, respectively,
      while the area of winter cereals has increased markedly (>70%). However, European
      brown hare numbers were primarily negatively associated with the number of red
      fox. Finally, we also found a positive association between mild winters and
      European brown hare numbers. CONCLUSION: The decline of Danish European brown
      hare populations can mainly be attributed to predation by red fox, but the
      development in agricultural land-use during the last 45 years have also affected
      the European brown hare numbers negatively. Additionally, though mild winters
      were beneficial to European brown hares, the increasing frequency of mild winters
      during the study period was insufficient to reverse the negative population
      trend.

PMID- 15479473
TI  - Current practices in the spatial analysis of cancer: flies in the ointment.
AB  - While many lessons have been learned from the spatial analysis of cancer, there
      are several caveats that apply to many, if not all such analyses. As "flies in
      the ointment", these can substantially detract from a spatial analysis, and if
      not accounted for, can lead to weakened and erroneous conclusions. This paper
      discusses several assumptions and limitations of spatial analysis, identifies
      problems of scientific inference, and concludes with potential solutions and
      future directions.

PMID- 15479475
TI  - In vitro pharmacokinetics of anti-psoriatic fumaric acid esters.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory skin disease that can be
      successfully treated with a mixture of fumaric acid esters (FAE) formulated as
      enteric-coated tablets for oral use. These tablets consist of dimethylfumarate
      (DMF) and salts of monoethylfumarate (MEF) and its main bioactive metabolite is
      monomethylfumarate (MMF). Little is known about the pharmacokinetics of these
      FAE. The aim of the present study was to investigate the hydrolysis of DMF to MMF
      and the stability of MMF, DMF and MEF at in vitro conditions representing
      different body compartments. RESULTS: DMF is hydrolyzed to MMF in an alkaline
      environment (pH 8), but not in an acidic environment (pH 1). In these conditions
      MMF and MEF remained intact during the period of analysis (6 h). Interestingly,
      DMF was hardly hydrolyzed to MMF in a buffer of pH 7.4, but was rapidly
      hydrolyzed in human serum having the same pH. Moreover, in whole blood the half
      life of DMF was dramatically reduced as compared to serum. The concentrations of
      MMF and MEF in serum and whole blood decreased with increasing time. These data
      indicate that the majority of the FAE in the circulation are metabolized by one
      or more types of blood cells. Additional experiments with purified blood cell
      fractions resuspended in phosphate buffered saline (pH 7.4) revealed that at
      concentrations present in whole blood monocytes/lymphocytes, but not granulocytes
      and erythrocytes, effectively hydrolyzed DMF to MMF. Furthermore, in agreement
      with the data obtained with the pure components of the tablet, the enteric-coated
      tablet remained intact at pH 1, but rapidly dissolved at pH 8. CONCLUSION:
      Together, these in vitro data indicate that hydrolysis of DMF to MMF rapidly
      occurs at pH 8, resembling that within the small intestines, but not at pH 1
      resembling the pH in the stomach. At both pHs MMF and MEF remained intact. These
      data explain the observation that after oral FAE intake MMF and MEF, but not DMF,
      can be readily detected in the circulation of human healthy volunteers and
      psoriasis patients.

PMID- 15479474
TI  - Using animal models to determine the significance of complement activation in
      Alzheimer's disease.
AB  - Complement inflammation is a major inflammatory mechanism whose function is to
      promote the removal of microorganisms and the processing of immune complexes.
      Numerous studies have provided evidence for an increase in this process in areas
      of pathology in the Alzheimer's disease (AD) brain. Because complement activation
      proteins have been demonstrated in vitro to exert both neuroprotective and
      neurotoxic effects, the significance of this process in the development and
      progression of AD is unclear. Studies in animal models of AD, in which brain
      complement activation can be experimentally altered, should be of value for
      clarifying this issue. However, surprisingly little is known about complement
      activation in the transgenic animal models that are popular for studying this
      disorder. An optimal animal model for studying the significance of complement
      activation on Alzheimer's - related neuropathology should have complete
      complement activation associated with senile plaques, neurofibrillary tangles (if
      present), and dystrophic neurites. Other desirable features include both
      classical and alternative pathway activation, increased neuronal synthesis of
      native complement proteins, and evidence for an increase in complement activation
      prior to the development of extensive pathology. In order to determine the
      suitability of different animal models for studying the role of complement
      activation in AD, the extent of complement activation and its association with
      neuropathology in these models must be understood.

PMID- 15479477
TI  - The evolution of drug-activated nuclear receptors: one ancestral gene diverged
      into two xenosensor genes in mammals.
AB  - BACKGROUND: Drugs and other xenobiotics alter gene expression of cytochromes P450
      (CYP) by activating the pregnane X receptor (PXR) and constitutive androstane
      receptor (CAR) in mammals. In non-mammalian species, only one xenosensor gene has
      been found. Using chicken as a model organism, the aim of our study was to
      elucidate whether non-mammalian species only have one or two xenosensors like
      mammals. RESULTS: To explore the evolutionary aspect of this divergence, we tried
      to identify additional xenobiotic sensing nuclear receptors in chicken using
      various experimental approaches. However, none of those revealed novel
      candidates. Ablation of chicken xenobiotic receptor (CXR) function by RNAi or
      dominant-negative alleles drastically reduced drug-induction in a chicken
      hepatoma cell line. Subsequently, we functionally and structurally characterized
      CXR and compared our results to PXR and CAR. Despite the high similarity in their
      amino acid sequence, PXR and CAR have very distinct modes of activation. Some
      aspects of CXR function, e.g. direct ligand activation and high promiscuity are
      very reminiscent of PXR. On the other hand, cellular localization studies
      revealed common characteristics of CXR and CAR in terms of cytoplasmic-nuclear
      distribution. Finally, CXR has unique properties regarding its regulation in
      comparison to PXR and CAR. CONCLUSION: Our finding thus strongly suggest that CXR
      constitutes an ancestral gene which has evolved into PXR and CAR in mammals.
      Future studies should elucidate the reason for this divergence in mammalian
      versus non-mammalian species.

PMID- 15479478
TI  - Using GIS technology to identify areas of tuberculosis transmission and
      incidence.
AB  - BACKGROUND: Currently in the U.S. it is recommended that tuberculosis screening
      and treatment programs be targeted at high-risk populations. While a strategy of
      targeted testing and treatment of persons most likely to develop tuberculosis is
      attractive, it is uncertain how best to accomplish this goal. In this study we
      seek to identify geographical areas where on-going tuberculosis transmission is
      occurring by linking Geographic Information Systems (GIS) technology with
      molecular surveillance. METHODS: This cross-sectional analysis was performed on
      data collected on persons newly diagnosed with culture positive tuberculosis at
      the Tarrant County Health Department (TCHD) between January 1, 1993 and December
      31, 2000. Clinical isolates were molecularly characterized using IS6110-based
      RFLP analysis and spoligotyping methods to identify patients infected with the
      same strain. Residential addresses at the time of diagnosis of tuberculosis were
      geocoded and mapped according to strain characterization. Generalized estimating
      equations (GEE) analysis models were used to identify risk factors involved in
      clustering. RESULTS: Evaluation of the spatial distribution of cases within zip
      code boundaries identified distinct areas of geographical distribution of same
      strain disease. We identified these geographical areas as having increased
      likelihood of on-going transmission. Based on this evidence we plan to perform
      geographically based screening and treatment programs. CONCLUSION: Using GIS
      analysis combined with molecular epidemiological surveillance may be an effective
      method for identifying instances of local transmission. These methods can be used
      to enhance targeted screening and control efforts, with the goal of interruption
      of disease transmission and ultimately incidence reduction.

PMID- 15479480
TI  - Preclinical data targeting vascular endothelial growth factor in colorectal
      cancer.
AB  - Vascular endothelial growth factor (VEGF) is the driving force behind
      angiogenesis in most solid malignancies. This also holds true for colorectal
      cancer (CRC), where increased levels of VEGF in primary cancers are associated
      with increased microvessel density and poor prognosis. These findings have led to
      preclinical studies evaluating the efficacy of anti-VEGF therapy in inhibiting
      the growth of CRC in ectopic and orthotopic locations. In preclinical models,
      numerous approaches to inhibit VEGF activity led to decreased tumor growth and
      angiogenesis. These studies led to clinical trials in which, unfortunately,
      single-agent anti-VEGF therapy was relatively ineffective for patients with
      metastatic CRC. However, combinations of anti-VEGF therapies with chemotherapy
      have clearly demonstrated clinical benefit. Understanding the mechanisms of the
      role of VEGF in CRC angiogenesis and the effect of anti-VEGF therapy on the tumor
      vasculature will allow oncologists to optimize therapeutic regimens targeting
      VEGF and its receptors.

PMID- 15479481
TI  - Integrating the anti-VEGF-A humanized monoclonal antibody bevacizumab with
      chemotherapy in advanced colorectal cancer.
AB  - Recent advances in the treatment of colorectal cancer (CRC) include the
      incorporation of new drugs to treat a disease where only one drug was known to be
      active. Oxaliplatin and irinotecan have been incorporated into 5-fluorouracil (5
      FU)-based regimens where they have increased response rates and survival.
      Targeted therapies against the epidermal growth factor pathway and the vascular
      endothelial growth factor (VEGF) pathway are also on the forefront of oncology
      research, and are beginning to play a role in the treatment of CRC. Current
      research efforts are trying to optimize the integration of targeted therapies
      into chemotherapy regimens such as IFL (irinotecan/bolus 5-FU/leucovorin [LV]),
      FOLFIRI (irinotecan/infusional 5-FU/LV), and FOLFOX (oxaliplatin/infusional 5
      FU/LV). In this article, the incorporation of the monoclonal antibody bevacizumab
      into the IFL regimen will be reviewed in detail. Bevacizumab targets VEGF-A, an
      important angiogenesis signaling factor commonly expressed in metastatic CRC. The
      addition of bevacizumab to the IFL regimen significantly increased response
      rates, median time to progression, and overall survival in patients receiving
      first-line treatment for CRC, thus leading the Food and Drug Administration to
      approve bevacizumab for the treatment of CRC in combination with 5-FU-based
      regimens. Bevacizumab treatment is associated with an increased rate of
      hypertension. In addition, there may be slight (1%-2%) but relevant increased
      risks related to gastrointestinal perforations and cardiovascular events. A
      modest increased risk of wound healing complications was observed in patients who
      underwent surgery while still receiving, or shortly after receiving, bevacizumab.
      Bevacizumab plus 5-FU is also a highly active first-line regimen. The role of
      bevacizumab with other first-line combination regimens, as well as its activity
      in the second-line setting, is now being determined by ongoing clinical trials.

PMID- 15479482
TI  - Can inhibition of angiogenic pathways increase the efficacy of intravenous 5
      fluorouracil-based regimens?
AB  - First-line irinotecan-containing regimens are toxic and may not be tolerated well
      by all patient subgroups. Trials evaluating less toxic regimens include a
      randomized, double-blind, multicenter study (AVF2192g) assessing 5-fluorouracil
      (5-FU)/leucovorin (LV) with bevacizumab. Patients were randomized to 1 of 2
      treatment arms. In arm 1, patients received LV intravenously (I.V.) over 2 hours
      and 5-FU I.V. over 1 hour every week for 6 weeks of an 8-week cycle, and
      bevacizumab 5 mg/kg was administered I.V. over 30-90 minutes every 2 weeks. In
      the second arm, patients received LV and 5-FU as in arm 1, and placebo I.V. over
      30-90 minutes every 2 weeks. The primary objective was duration of survival.
      Eligible patients with untreated metastatic colorectal cancer (CRC) were >or= 65
      years of age, had an Eastern Cooperative Oncology Group performance status of
      1/2, a serum albumin level <or= 3.5 g/dL, or had previous radiation therapy to
      the pelvis or abdomen. Preliminary results indicated a median survival of 12.9
      months versus 16.6 months on the placebo and bevacizumab arms, respectively (P =
      0.159). Progression-free survival was 5.5 months in the placebo arm compared to
      9.2 months in the bevacizumab arm. The overall response rate was 15% in the
      placebo arm and 26% in the bevacizumab arm. The percentages of patients
      experiencing toxicities typically associated with 5-FU/LV were similar in both
      arms. Toxicities most associated with bevacizuamb included bleeding, thrombolic
      events, hypertension, and proteinuria. Growing evidence indicates that
      bevacizumab is an effective agent in CRC when added to several chemotherapy
      combinations. The current study indicates that subpopulations of patients with
      advanced age or poor performance status could be treated successfully with 5
      FU/LV in combination with bevacizumab without excessive toxicities.

PMID- 15479483
TI  - Combining anti-VEGF approaches with oxaliplatin in advanced colorectal cancer.
AB  - Angiogenesis, the formation of blood vessels, is a vital process in tumor growth
      and metastasis. Vascular endothelial growth factor (VEGF) is a potential target
      for antiangiogenic therapy because its overexpression has been associated with
      tumor vascularity, poor prognosis, and aggressive disease in many malignancies,
      including colorectal cancer (CRC). Bevacizumab is a recombinant humanized
      monoclonal antibody against VEGF. It is the first angiogenesis inhibitor to show
      significant activity in patients and, when combined with chemotherapy, leads to a
      significant survival benefit in CRC. This monoclonal antibody has been approved
      for first-line therapy in combination with intravenous 5-fluorouracil-containing
      regimens in patients with metastatic CRC. Vatalanib (PTK787/ZK222584) is an oral
      antiangiogenic tyrosine kinase inhibitor of the VEGF receptor. Currently, it is
      being evaluated in combination with FOLFOX (5
      fluorouracil/leucovorin/oxaliplatin) in metastatic CRC. This article reviews the
      process of angiogenesis and the successful translation of antiangiogenic agents
      into the clinic. Specifically, studies evaluating VEGF-targeted agents in
      combination with oxaliplatin-containing regimens in CRC are discussed.

PMID- 15479484
TI  - Use of soluble recombinant decoy receptor vascular endothelial growth factor trap
      (VEGF Trap) to inhibit vascular endothelial growth factor activity.
AB  - Primary tumors and metastases require blood vessel formation to support their
      continued growth and eventual metastasis. They use existing vasculature during
      initial growth but eventually must orchestrate the development and maintenance of
      new vessels--a process termed angiogenesis--to grow beyond a small size and
      spread. Angiogenesis is regulated by a number of soluble factors, the relative
      proportions of which can exacerbate or inhibit the process. Vascular endothelial
      growth factor (VEGF) is a potent stimulator of angiogenesis, produced by the
      majority of human solid tumors. Inhibitors of VEGF might have an impact on the
      growth and metastasis of these cancers. The relevance of this strategy to the
      treatment of colorectal cancer was first successfully demonstrated in human
      clinical trials using a monoclonal antibody against VEGF. A potent antiangiogenic
      soluble recombinant decoy, VEGF Trap is a protein constructed from VEGF receptor
      binding domains linked to an immunoglobulin G(1) constant region. It possesses an
      affinity for VEGF that is significantly higher than that of the monoclonal
      antibody. VEGF Trap has demonstrated marked efficacy in halting angiogenesis and
      shrinking tumors in preclinical animal models and is currently being studied in
      phase I clinical trials in humans with advanced solid malignancies.

PMID- 15479485
TI  - Future directions with angiogenesis inhibitors in colorectal cancer.
AB  - The recent US Food and Drug Administration's approval of bevacizumab has
      reinvigorated antiangiogenic research and has moved colorectal cancer to the
      forefront of study for the most promising drug candidates in this class.
      Predicting future directions in this field requires a return to the challenges of
      the past. Antiangiogenic drugs have necessitated new study design paradigms and
      imaging techniques in the assessment of drug activity and in dose selection. The
      success of bevacizumab and the promise of vatalanib (PTK787/ZK222584) and the
      cyclooxygenase-2 inhibitors also illustrate the importance of these adaptations.
      A better understanding of the determinants of response to antiangiogenic agents
      and their mechanisms of action, especially in combination with cytotoxic drugs,
      is crucial to future drug development.

PMID- 15479486
TI  - Prostate cancer and bone: a unique relationship with multiple opportunities for
      targeted therapy.

PMID- 15479487
TI  - Highlights from the 40th Annual Meeting of the American Society of Clinical
      Oncology, New Orleans, LA. June 2004.

PMID- 15479488
TI  - Benefit of extended zoledronate therapy for patients with bone metastases from
      hormone-refractory prostate cancer.

PMID- 15479489
TI  - Activity of epothilone B analogues ixabepilone and patupilone in hormone
      refractory prostate cancer.

PMID- 15479490
TI  - Double primary cancers of the prostate and bladder: a literature review.
AB  - A number of studies report a high frequency of double primary cancers of the
      bladder and prostate. The coincidence was as high as 70% for prostate cancers in
      patients with bladder cancer, and 3.4% for bladder cancers in patients with
      prostate cancer. Two studies reviewing medical records reported a significant
      risk of bladder cancer after prostate cancer and of prostate cancer after bladder
      cancer. Only 1 of 3 cancer registry studies reported a significantly increased
      risk of prostate cancer after bladder cancer, and 3 of 11 studies reported a
      significantly increased risk in bladder cancer after prostate cancer. There was
      an association between DNA repair and N-acetyltransferase polymorphisms and risk
      of prostate and bladder cancer. These data suggest that these cancers may share a
      common carcinogenic process or that these patients are particularly susceptible
      to both cancers. Because of the association between these cancers, patients who
      are diagnosed with prostate or bladder cancer should be followed closely for the
      detection of the second urologic malignancy.

PMID- 15479491
TI  - Current concepts in the management of erectile dysfunction in men with prostate
      cancer.
AB  - Development in the management of prostate cancer has placed increased attention
      on patient quality of life after treatment, particularly sexual function. The
      incidence of erectile dysfunction (ED) in men following radical prostatectomy has
      been estimated to range from 16% to 82%. Several factors determine the
      postoperative incidence of erectile difficulties; these include patient age,
      degree of cavernosal nerve sparing during surgery, cancer stage, and associated
      comorbidities. Early initiation of available treatments after radical
      prostatectomy, such as phosphodiesterase-5 (PDE-5) inhibitors and intracavernosal
      alprostadil, may improve the speed and degree of recovery of erectile function.
      Oral PDE-5 inhibitors are recognized as the first line of therapy for men with ED
      after radical prostatectomy, with reasonable success rates reported for all
      commercially available PDE-5 inhibitors. In recognition of the neurogenic basis
      for erectile dysfunction after radical prostatectomy, new strategies have been
      devised, such as cavernous nerve graft interposition procedures, perioperative
      neuroprotection measures, and postoperative neurotrophic treatments. Hopefully,
      these efforts will improve quality of life for patients with prostate cancer. The
      aim of this article is to review the current modalities of ED management for men
      with prostate cancer.

PMID- 15479492
TI  - Effect of pelvic lymph node irradiation in salvage therapy for patients with
      prostate cancer with a biochemical relapse following radical prostatectomy.
AB  - Radiation therapy (RT) as salvage treatment for a biochemical relapse following
      prostatectomy has been shown to be of benefit measured by serum prostate-specific
      antigen (PSA) control. However, identifying a target volume for RT has not been
      well established in this setting. In this study, the results of postoperative RT
      delivered to extended fields (EFs), prostatic fossa, and pelvic lymph nodes
      encompassing at least the obturator lymph nodes are compared with treatment of
      limited fields (LFs), prostatic fossa only, as salvage treatment for patients
      with a biochemical relapse. Between 1987 and 1999, 68 patients were referred for
      postprostatectomy RT. Of these patients, 46 were treated for salvage intent by RT
      alone without adjuvant hormones, 21 patients were treated to EFs and 25 treated
      to LFs. All patients were treated using 4-field plans. The mean field sizes
      measured 15 x 14 cm (AP/PA fields) and 12 x 14 cm LFs for the EFs and 10 x 10 cm
      (AP/PA fields) and 10 x 10 cm (lateral fields) for the LFs. The mean total doses
      for the EFs and LFs were 6300 and 6200 cGy, respectively, using 180-cGy daily
      increments. All patients treated to the EFs received boost doses to the prostatic
      fossa after 4500 cGy total dose to the pelvis. The 10-year actuarial biochemical
      disease-free survival (DFS) rates for the EF and LF groups were 52% and 47%,
      respectively (P = 0.523). The distant metastasis-free survival (DMFS) rates were
      77% and 78% (P = 0.925), and overall survival (OS) rates were 88% and 68% (P =
      0.615) for the EF and LF group, respectively. A subset analysis of patients with
      adverse pathologic features (including tumor-involved surgical margins, lymph
      node involvement, seminal vesicle involvement, extracapsular extension, and/or
      perineural invasion) showed biochemical DFS rates of 57% and 44% (P = 0.217) for
      the EF and LF groups, respectively. The DMFS rates were 84% and 72% (P = 0.423),
      and OS rates 92% and 61% (P = 0.366) for the EF and LF groups, respectively. For
      patients with increasing PSA levels after a radical prostatectomy, salvage
      irradiation is a viable option for biochemical control. Our results suggest that
      EF radiation with coverage of pelvic lymph nodes shows a trend toward better PSA
      control in those with adverse pathologic features, although statistical
      significance was not achieved because of the limited number of patients who
      satisfied the restricted criteria excluding use of adjuvant hormones.

PMID- 15479493
TI  - Absence of a correlation of androgen receptor gene CAG repeat length and prostate
      cancer risk in an African-American population.
AB  - Shorter androgen receptor gene CAG repeat length has been associated with an
      increased risk of prostate cancer, an earlier age of onset, and more advanced
      stage of disease. Studies comparing the distribution of CAG repeat lengths within
      different populations have reported that racial groups with higher prostate
      cancer incidence also have shorter CAG repeat lengths. We evaluated CAG repeat
      length in 685 black men in Louisiana, South Carolina, and the District of
      Columbia who were participating in prostate cancer screening, comparing the 118
      who were diagnosed with prostate cancer with 567 who had normal serum prostate
      specific antigen levels and no evidence of cancer on digital rectal examination.
      The median CAG repeat length was 21 among cases and 19 among controls (P = 0.11).
      Cases were significantly older than controls, with a median age of 68 years
      compared with 54 years (P < 0.0001). After adjusting for age, we found no
      association between prostate cancer risk and CAG repeat length (odds ratio, 1.05;
      95% CI, 0.98-1.13; P = 0.16). Dividing CAG repeat lengths into septiles and
      calculating the odds ratio for each revealed no specific repeat-length range with
      a significantly elevated or depressed risk of prostate cancer, but a trend test
      showed a significant association between longer CAG repeat lengths and an
      elevated risk of prostate cancer (P = 0.02). Neither grade nor stage was
      associated with CAG repeat length. This study confirms earlier reports that black
      men have shorter CAG repeat lengths than reported white and Asian populations. We
      did not find an increased risk of prostate cancer among black men with fewer CAG
      repeats.

PMID- 15479494
TI  - Phase II randomized trial of weekly paclitaxel with or without estramustine
      phosphate in progressive, metastatic, hormone-refractory prostate cancer.
AB  - This study was conducted to determine the similarity of response rates and safety
      produced by weekly paclitaxel with or without oral estramustine in patients with
      metastatic hormone-refractory prostate cancer. Between December 1998 and December
      1999, 163 patients were randomized to receive 28-day cycles of paclitaxel 100
      mg/m2 on days 2, 9, and 16 plus estramustine 280 mg orally 3 times a day on days
      1-3, 8-10, and 15-17, or to receive paclitaxel 100 mg/m2 alone on days 1, 8, and
      15. Objective response was defined as a > oe = 50% decrease in prostate-specific
      antigen (PSA) maintained for 4 weeks with stable or improved performance status.
      Response rates included 37 partial responses for paclitaxel/estramustine (47%)
      and 22 partial responses for paclitaxel (27%; P < 0.01). Median duration of
      response was 15.1 months for paclitaxel/estramustine and 15.5 months for
      paclitaxel; median survival was 16.1 months and 13.1 months, respectively (P =
      0.049). Common toxicities for both treatments included neutropenia,
      gastrointestinal events, neuropathy, and asthenia. Thromboembolic events were
      more frequent in the paclitaxel/estramustine arm (no prophylactic
      anticoagulants). The rate of PSA decline for paclitaxel/estramustine was almost 2
      times that of paclitaxel (47% vs. 27%), with acceptable toxicity. Multivariate
      analysis of prognostic factors affecting survival was not significant for
      treatment arm (P = 0.08). Although the incidence of thromboembolic events
      appeared to be increased in the paclitaxel/ estramustine arm, the addition of
      estramustine was responsible for a 20% increase in the rate of PSA decline.
      Neither treatment arm had significant impact on quality of life as measured by
      the Functional Assessment of Cancer Therapy-Prostate quality of life
      questionnaire. This study produced encouraging data; further studies of
      paclitaxel/ estramustine are recommended.

PMID- 15479495
TI  - Anti-CD3 x anti-HER2 bispecific antibody effectively redirects armed T cells to
      inhibit tumor development and growth in hormone-refractory prostate cancer
      bearing severe combined immunodeficient beige mice.
AB  - The bispecific antibody (BiAb) anti-CD3 x anti-Her2/neu (Her2Bi), combines
      Her2/neu targeting with nonmajor histocompatibility complex-restricted
      cytotoxicity mediated by activated T cells (ATCs). To evaluate this adaptive
      immunotherapeutic strategy for augmenting antitumor immune response toward
      hormone-refractory prostate cancer (HRPC), normal donor or patient T cells were
      activated with anti-CD3, expanded ex vivo in interleukin-2, and then armed with
      Her2Bi (5-500 ng per million ATCs). In vitro, arming ATCs with Her2Bi increased
      the percent specific cytotoxicity toward PC-3 prostate adenocarcinoma cells 2-3
      fold and increased the secretion of Th1 cytokines granulocyte-macrophage colony
      stimulating factor, tumor necrosis factor-alpha, and interferon-gamma when
      compared with unarmed ATCs or ATCs armed with an irrelevant BiAb. Her2Bi-armed
      ATCs administered with PC-3 (Winn Assay) or injected intratumorally prevented
      development or induced remissions, respectively, of PC-3 tumors in severe
      combined immunodeficient beige mice. Intravenously administered Her2Bi-armed ATCs
      localized to PC-3 xenografts mediated cytotoxicity toward tumor cells and
      produced significant tumor growth delay of PC-3 tumors, but not Her2/neu-negative
      LS174T colon adenocarcinoma xenografts. By flow cytometry analyses, Her2Bi-armed
      ATCs had a proliferative advantage over unarmed ATCs and persisted in the
      circulation and tumor tissues longer than unarmed ATCs. These findings suggest
      that Her2Bi-armed ATC therapy may be an effective, nontoxic, tumor-specific
      treatment for Her2-positive HRPC.

PMID- 15479496
TI  - Second-line chemotherapy for hormone-refractory prostate cancer: has the time
      come?
AB  - Prostate-specific antigen testing has not only led to an earlier diagnosis of
      prostate cancer, but also to an earlier identification of hormone-refractory
      prostate cancer (HRPC). Many patients identified early with HRPC may receive
      first-line taxane-based chemotherapy. Patients who progress after first-line
      chemotherapy are still quite healthy and desire further therapy. No proven
      treatment options exist for the second-line treatment of HRPC. Finding new agents
      that are active in the second-line setting and identifying relevant outcome
      variables and predictive pretreatment variables are crucial in improving survival
      and quality of life for this patient population.

PMID- 15479497
TI  - The 'bear trap': the colliding epidemics of tuberculosis and HIV in Russia.
AB  - In April, 2003 the World Bank approved a long-awaited $150 million loan to the
      Russian Federation to support tuberculosis (TB) and AIDS control. Although the
      Russian Federation accounts for a relatively small fraction of the global TB case
      load the proportion of cases which are drug-resistant and particularly multidrug
      resistant is very high in some regions. HIV incidence, principally associated
      with intravenous drug abuse, has also increased dramatically and this will impact
      upon TB control efforts. Federation-wide data are limited but a focus on one
      region shows something of the confluence of the epidemics of HIV and TB.
      Approaching 200 cases of HIV-associated TB have occurred in the past two years,
      and the age structure of the HIV-infected population and that with high rates of
      TB shows sizeable overlap. The region has high rates of multidrug-resistant TB
      which are likely to impact considerably on efforts to meet this emerging and
      complex public health challenge. Insights gained through the examination of this
      one region can tell us something of the magnitude of the challenge now faced by
      both the international community and Russia.

PMID- 15479498
TI  - The National Sexual Health and HIV Strategy: where are we?

PMID- 15479499
TI  - BASHH survey of additional genitourinary medicine-targeted allocations in 2003
      and 2004.
AB  - In response to the increasing waiting times for appointments at genitourinary
      (GU) medicine clinics, the Department of Health has made three targeted funding
      allocations to improve access consisting of a non-recurrent allocation of 5
      million pounds in 2002-03, followed by an 8 million pounds recurrent and a
      further 5 million pounds non-recurrent allocation in 2003-04. The British
      Association for Sexual Health and HIV (BASHH) conducted a survey of lead
      consultants for GU medicine clinics in March 2004 to determine if they could
      confirm whether all of the targeted funding had been allocated to their budgets.
      A total of 122 individuals representing 132 (65%) clinics in England, responded
      to the questionnaire for either calendar year. Of the first 5 million pounds non
      recurrent allocation, made in January 2003, the number and percentage of the 117
      respondents who had received their full allocation was 96 (82%) compared to 13
      (11%) who received less than the allocated amount and 8 (7%) who were uncertain.
      These individuals were able to confirm that 3,155,000 pounds (92%) of the
      3,424,500 pounds allocation to their clinics had reached its intended target. Of
      the second 8 million pounds recurrent allocation in financial year 2003-04, 76
      (64%) of 119 respondents received their full allocation, 30 (25%) respondents
      received less than the allocated amount, and 13 (11%) respondents were uncertain.
      The total amount of the allocation for the clinics represented by these 106
      recipients was 4,566,500 pounds of which 3,619,663 pounds (79%) had reached their
      clinic budgets. Of the final non-recurrent 5 million pounds allocation in
      financial year 2003-04, 61 (51%) respondents received their full allocation, 49
      (41%) respondents received less than their allocated amount, and nine (8%)
      respondents remained uncertain. The total amount of the allocation for the
      clinics represented by these 110 recipients was 3,258,000 pounds of which
      1,638,000 pounds (50%) had reached their clinic budgets. Thus, of the total
      7,824,500 pounds allocation to the Primary Care Trusts (PCTs) with lead sexual
      health responsibilities for the GU medicine clinics of recipients in 2003-04,
      only 5,257,663 pounds (67%) was confirmed to have reached clinic budgets.
      Overall, only 51 (43%) of 119 respondents could confirm having received all of
      their recurrent and non-recurrent allocations, 58 (49%) had received either a
      reduced allocation or none at all and 10 (8%) were uncertain. This survey
      suggests that a significant proportion of the additional funding to improve
      access to GU medicine clinics failed to reach its intended target. The deficit
      between the amounts allocated and received by clinics was larger in financial
      year 2003-04, when the funding was given to PCTs with lead roles for sexual
      health, as compared with the preceding year when it was allocated directly to
      clinics. Moreover, the late allocation of non-recurrent funding and the inability
      of many clinics to arrange for this funding to be carried forward at year-end may
      have further prevented its intended use to increase service capacity and reduce
      waiting times.

PMID- 15479500
TI  - The impact of pump-priming funding on genitourinary medicine and modernization of
      services.
AB  - Genitourinary (GU) medicine services are under increasing pressure due to
      increased workload. The Department of Health responded to this crisis by
      allocating pump-priming funding of ?5 million direct to GU medicine clinics in
      2002-03. A survey was performed of all clinics in England to determine if funding
      was received, its utilization and the extent of modernization of services.
      Response rate was 71% (147 of 206 clinics), with 95% (140) receiving their
      allocation. Additional clinics were instated by 54% (74/137) and of these 51%
      (35/69) had thus reduced their waiting times. Extensive modernization of services
      was under way, with 89% (130/146) reducing proportion of follow-up attendances,
      87% (127/146) extending the nurse role and the majority of clinics looking at
      developing or extending their clinical networks. This study has shown the direct
      benefit of increased funding allocated to GU medicine and the extent of
      modernization under way.

PMID- 15479501
TI  - Dried blood spots are an acceptable and useful HIV surveillance tool in a remote
      developing world setting.
AB  - Enzyme-linked immunosorbent assay and Western blot analysis of dried blood spots
      (DBS) on filter paper have been shown to be as sensitive and specific as analysis
      of serum, and therefore may be a cost-effective and culturally appropriate HIV
      seroprevalence tool in remote areas. This study examines the acceptability of DBS
      in a tropical, rural population from an outpatient clinic in Andhra Pradesh,
      India, where participation was offered to every fifth patient seeking general
      medical care between March and April 2001. All 1413 patients approached for the
      study agreed to participate and provide a DBS for examination. The overall HIV
      seroprevalence in this sample was 2.8%. Of the participants, 51.7% were male,
      93.2% were between the ages of 18 and 40, 85.3% were married, 29.7% were
      employed, 47.6% had no education and 73.1% resided in a rural setting. In the
      univariate analysis, history of genital warts (P = 0.01), sexually transmitted
      disease (P = 0.001), premarital sexual intercourse (P = 0.002), sexual contact
      with a commercial sex worker (P = 0.003), being employed (P = 0.011) and having
      more than 10 injections for medical purposes (P = 0.006) all correlated with
      being HIV-infected. Given the uniform willingness of these clinic attendees to be
      tested, we conclude that DBS is a useful, cost-effective tool in HIV
      serosurveillance in a rural, tropical setting.

PMID- 15479503
TI  - Intrauterine infection after delivery: a marker of HIV-1 seropositivity among
      puerperal women in Uganda?
AB  - A case controlled study about HIV seroprevalence among women with post-partum
      endometritis-myometritis (PPEM) matched with two controls. Each was performed in
      a non-governmental organization hospital in Kampala, Uganda. All participants
      were offered HIV pre- and post-test counselling. Personal and clinical
      information was obtained and HIV-1 ELISA tests performed on blood samples and
      discordant results resolved by Western blot test. HIV-1 seroprevalence was
      significantly higher among women with PPEM than controls, 26 (42.3%) and 26
      (21.3%) respectively (P = 0.002). Women with PPEM were two-and-a-half times more
      likely to be HIV-positive than controls, odds ratio 2.74 (95% CI 1.34-5.65).
      Single or cohabiting women and low salaried women were also significantly more
      among PPEM cases than controls. In conclusion, PPEM cases had significantly
      higher seroprevalence of HIV-1 infection than controls and this needs further
      elucidation for purposes of management strategies.

PMID- 15479504
TI  - Caretakers of AIDS patients in rural Tanzania.
AB  - Socio-economic characteristics of caretakers of bed-ridden AIDS patients in two
      rural communities of Rungwe district, Tanzania were sought. The study also
      explored what caretaking entailed. Data were collected from 60 caretakers between
      September and November 2002. The proportion of female caretakers was
      significantly higher than that of male caretakers; the majority of the caretakers
      were old. The majority of the AIDS patients were family members of the
      caretakers. The caretakers' households lacked basic needs for the patients. Some
      of the caretakers sold family assets in order to buy medicines for the patients.
      Most of the caretakers worked under stress and there was no one to counsel them.
      Community members offered very little or no support to caretakers and the
      households were stigmatized. People in the communities knew about HIV/AIDS
      transmission, but their behaviour did not match their knowledge.

PMID- 15479502
TI  - Syphilis as a social disease: experience from the post-communist transition
      period in Estonia.
AB  - Increased incidence of sexually transmitted diseases (STD) and radical social
      changes have taken place at the same time in Estonia. Our aim was to study the
      trends in syphilis incidence, selected sociodemographic factors and health status
      indicators during the economic transition. Associations were estimated by the
      ordinary least square regression method for change in and actual values of
      syphilis and tuberculosis incidence rate (IR), percentage of non-ethnic Estonians
      and urban population, homicides rate, unemployment rate and, birth rate. The
      analysis was performed by counties at three different time periods. Syphilis IR
      significantly correlated with the proportion of non-ethnic Estonians, urban
      population, tuberculosis IR and birth rate. Change of syphilis IR correlated
      significantly with concurrent changes in unemployment rate and tuberculosis IR.
      Our findings support the theory that syphilis is a social disease, thus
      emphasizing the importance of social factors in the occurrence of STDs.

PMID- 15479505
TI  - Case fatality and health care costs in HIV-infected patients: evolution from 1992
      to 2000 at Rouen University Hospital, France.
AB  - Vital prognosis in HIV-infected patients has been improved by new therapies,
      leading to an increase in treatment and outpatient costs but lower inpatient care
      costs. The aim of the study was to compare the health care costs between 1992
      1996 (first half) and 1996-2000 (second half) in HIV-infected patients at Rouen
      University Hospital. Hospitalization costs (including inpatient and outpatient
      care), infectious complication treatment and antiretroviral therapy costs were
      evaluated from a National Health Insurance viewpoint. Between 1992 and 2000, 1212
      patients were admitted at least once. Total expenditure increased between the two
      periods from 13,660 Euro to 27,567 Euro, i.e., a two-fold increase. During the
      same period, 125 deaths were avoided, and 3602 years of life were gained. The
      cost of one avoided death was 108,320 Euro and the cost per life-year gained was
      3776 Euro.

PMID- 15479506
TI  - Perceptions toward HIV, HIV screening, and the use of antiretroviral medications:
      a survey of maternity-based health care providers in Zambia.
AB  - Mother-to-child transmission of HIV (MTCT) is a major contributor to Zambia's HIV
      burden. Based on our experience in Zambia, we felt that provider perceptions,
      knowledge base, and practice patterns toward HIV-positive mothers may pose as
      significant obstacles to preventing MTCT. Two hundred and twenty-five health care
      providers throughout Zambia were surveyed in 2002. Providers reported widespread
      stigma associated with HIV. Physicians (OR = 1.9), providers with research
      affiliations (OR = 2.3), and those located in Lusaka (OR = 9.0) were more likely
      to offer HIV testing. Only 30% routinely prescribed antiretroviral treatment
      (ART) to reduce MTCT. Practitioners from district facilities, those from Lusaka,
      and those employed at research facilities were more likely to prescribe ART
      routinely (OR = 2.8, 10.1 and 3.4 respectively). Among those never prescribing
      ART, most cited a lack of availability (83%). Our results highlight the need for
      further provider education, critical appraisal of the current system for HIV
      testing, and widespread distribution of ART.

PMID- 15479507
TI  - Epidemiology of adult and adolescent HIV infection in Israel: a country of
      immigration.
AB  - In Israel, the caseload and main modes of transmission have changed dramatically
      since 1991 after mass immigration from countries with generalized HIV epidemics.
      The previous annual average (of 60 new cases) has almost quadrupled, and 68% are
      among heterosexuals (compared with 11.6% before). We verified all HIV/AIDS cases
      ever documented, redefined (according to UNAIDS/WHO definitions) and analysed
      those aged 13+. Between 1980-2000, HIV and AIDS were diagnosed, respectively, in
      2204 and 682 adults and adolescents (cumulative HIV infection rate = 61/100 000).
      Of these, 65.2% are male (mean age 35.0 years old; SD = 11.0), 31.5% female (mean
      age 31.4 years old; SD = 10.5) (and 3.3%, sex unknown). The main modes of HIV
      transmission were heterosexual (45%), MSM (16.9%) and IDUs (11.5%). Prevention
      measures must be strengthened, if the currently low-level of HIV epidemic among
      the Israeli general population is to be sustained.

PMID- 15479508
TI  - Methamphetamine users in northern Thailand: changing demographics and risks for
      HIV and STD among treatment-seeking substance abusers.
AB  - Our objective was to determine sociodemographic, sexual and drug-use-related risk
      factors among methamphetamine (MA) users presenting for drug treatment in
      northern Thailand. Patients admitted for drug detoxification for MA and other
      drugs were studied cross-sectionally for risk factors associated with substance
      abuse and blood-borne and sexually transmitted pathogens. In all, 1865 (200
      women) patients treated for MA, opiate, and mixed substance abuse between 1
      February 1999 and 31 January 2000 completed all study procedures. Among 1865
      participants, 750 (40.2%) were admitted for MA detoxification and 1115 (59.8%)
      for opiate (heroin, opium, or both) treatment. MA users were significantly
      younger, better educated, more likely to be Thai than highland ethnic minorities,
      and had significantly different sexual risks and sexually transmitted disease
      rates, including lower syphilis seropositivity and higher chlamydial prevalence,
      than persons admitted for opiate or mixed drug treatment. For those who reported
      MA use only, use by injection was rare and HIV infections significantly less
      common than among all other drug users. Thailand is undergoing an epidemic of MA
      use. These young users are a strikingly different population from opiate/heroin
      users in northern Thailand. MA users had higher rates of chlamydia infection than
      opiate users, reflecting their young age, and HIV rates in this population were
      lower than injecting drug users, but still elevated. MA use is a serious public
      health problem in Thailand and both improved prevention and treatment
      methodologies are urgently needed.

PMID- 15479509
TI  - A case of asymptomatic gonorrhoea in a male using illegal steroids.
AB  - Acute gonococcal urethritis is usually a symptomatic infection in males. Most men
      will present within one or two weeks after an exposure with symptoms of urethral
      discharge and dysuria. Early diagnosis is possible in genitourinary medicine
      clinics with typical signs and symptoms along with microscopy awaiting
      confirmation by culture and sensitivities. We report a case of gonorrhoea in
      which we believe the symptoms were masked due to regular use of steroids in a
      body builder.

PMID- 15479510
TI  - Pseudomonas orchitis in puberty.
AB  - Acute epididymo-orchitis is a common cause of 'acute scrotum' in adolescence and
      young adults, and the common causative pathogens are Chlamydia trachomatis and
      Neisseria gonorrhoeae. This is a rare case of acute epididymo-orchitis due to
      Pseudomonas aeruginosa in a pubertal boy with a history of 'ano-receptive'
      intercourse. On Medline search there are no reports of pseudomonas orchitis in
      this age group.

PMID- 15479511
TI  - HIV in Africa - still a major matter of unsafe sex.

PMID- 15479512
TI  - AIN and the GUM specialist.

PMID- 15479516
TI  - Molecular beacon DNA probes and their bioanalytical applications.

PMID- 15479517
TI  - Determination of the maximum temperature at the center of an optically thick
      laser-induced plasma using self-reversed spectral lines.
AB  - A method of temperature measurement based on the model developed by Bartels of an
      optically thick inhomogeneous plasma was applied to a laser plasma induced on a
      target containing barium. The method involves the intensity ratio measurement of
      two self-reversed Ba(II) lines. The temperature thus determined corresponds to
      the maximum temperature in the plasma center. The plasma temperature was measured
      for delay times between 0.5 micros and 10 micros in two spectrometer operating
      modes: the scanning mode and the dual-wavelength mode, the latter resulting in
      better precision. A detailed analysis of experimental errors was performed. The
      error strongly depended on the wavelength separation of the lines used. The most
      accurate results were obtained for the largest line separation. Using one line in
      the UV and the other in the visible region, the relative error was 2-6% for
      temperatures between 8000 K and 20 000 K. The distribution of the plasma
      temperature along the plasma height was measured in the same delay time range.
      The temperature was found to be uniform along the plasma vertical axis, thus
      confirming the plasma cylindrical symmetry.

PMID- 15479518
TI  - Electron density and gas temperature from line broadening in an argon surface
      wave-sustained discharge at atmospheric pressure.
AB  - We have used the collisional broadening of neutral argon lines to determine the
      electron density and gas temperature of a microwave discharge at atmospheric
      pressure. The gas temperature can be obtained from the Van der Waals broadening,
      provided that the Stark broadening is negligible. This can be achieved by using
      lines from low-lying levels (close to the ground state). On the other hand, lines
      corresponding to transitions from high-lying levels, which are more sensitive to
      Stark (quadratic) broadening, can be utilized to determine electron density. The
      electron density values obtained from the quadratic Stark broadening of argon
      atoms are in reasonable agreement with those derived from the linear Stark
      broadening of the H(beta) line. The proposed method ensures perturbation-free
      access to plasma parameters, which is not the case when adding hydrogen to the
      discharge, even in a small amount, to observe the Balmer series lines.

PMID- 15479519
TI  - A non-lensed fiber-optic resonance-enhanced multiphoton ionization probe.
AB  - We have developed a miniature fiber-optic probe with no focusing optics for in
      situ analysis of volatile organic compounds (VOCs). The probe uses an optical
      fiber to transmit a laser pulse to a vapor sample causing it to ionize adjacent
      to the fiber tip through a resonance-enhanced multiphoton ionization (REMPI)
      process. The distal end of the optical fiber is contained co-axially within 2-mm
      inner-diameter stainless steel tubing that serves as an electrode. The electrode
      is biased at a high positive potential to collect electrons. The current
      generated is shown to be proportional over about two orders of magnitude to the
      concentration of the species ionized. Visible wavelength REMPI spectroscopy is
      used to determine probe sensitivities of 20 ppb (benzene) and 43 ppb (toluene).
      Designing the probe without focusing optics specifies an achromatic ionization
      region constant in size and position as the laser wavelength is scanned, which
      simplifies data collection and reduction. Focusing achromatic systems are
      discussed and the potential signal improvement is estimated.

PMID- 15479520
TI  - Determination of depleted uranium in urine via isotope ratio measurements using
      large-bore direct injection high efficiency nebulizer-inductively coupled plasma
      mass spectrometry.
AB  - Inductively coupled plasma mass spectrometry (ICP-MS), coupled with a large-bore
      direct injection high efficiency nebulizer (LB-DIHEN), was utilized to determine
      the concentration and isotopic ratio of uranium in 11 samples of synthetic urine
      spiked with varying concentrations and ratios of uranium isotopes. Total U
      concentrations and (235)U/(238)U isotopic ratios ranged from 0.1 to 10 microg/L
      and 0.0011 and 0.00725, respectively. The results are compared with data from
      other laboratories that used either alpha-spectrometry or quadrupole-based ICP-MS
      with a conventional nebulizer-spray chamber arrangement. Severe matrix effects
      due to the high total dissolved solid content of the samples resulted in a 60 to
      80% loss of signal intensity, but were compensated for by using (233)U as an
      internal standard. Accurate results were obtained with LB-DIHEN-ICP-MS, allowing
      for the positive identification of depleted uranium based on the (235)U/(238)U
      ratio. Precision for the (235)U/(238)U ratio is typically better than 5% and 15%
      for ICP-MS and alpha-spectrometry, respectively, determined over the
      concentrations and ratios investigated in this study, with the LB-DIHEN-ICP-MS
      system providing the most accurate results. Short-term precision (6 min) for the
      individual (235)U and (238)U isotopes in synthetic urine is better than 2% (N =
      7), compared to approximately 5% for conventional nebulizer-spray chamber
      arrangements and >10% for alpha-spectrometry. The significance of these
      measurements is discussed for uranium exposure assessment of Persian Gulf War
      veterans affected by depleted uranium ammunitions.

PMID- 15479521
TI  - Assessing soil respiration by means of near-infrared diode laser spectroscopy.
AB  - High-resolution diode laser spectroscopy in the near-infrared region is applied
      to the accurate measurement of soil respiration. In particular, the use of a
      diode-laser-based spectrometer has allowed the implementation, for the first
      time, of a static accumulation method capable of measuring soil respiration from
      continuous measurements of CO(2) concentrations, with minor perturbation on soil
      respiration as well as on CO(2) transport and emission. The system has been
      tested in a laboratory experiment by detection of CO(2) production from sandy
      matrices, inoculated with active soil microbes and supplied with different
      amounts of decomposable plant material. Respiration rates of all samples were
      then retrieved using a diffusion model. The results of the laboratory tests are
      in agreement with those expected on the basis of sample composition. Examples of
      operation with real soil samples are also reported. We discuss the possible field
      application of the system, in conjunction with closed static soil chambers.

PMID- 15479522
TI  - Extension of fourier transform vibrational circular dichroism into the near
      infrared region: continuous spectral coverage from 800 to 10 000 cm(-1).
AB  - We report the first vibrational circular dichroism (VCD) spectra with continuous
      coverage from 800 cm(-1) in the mid-infrared (MIR) region to 10 000 cm(-1) in the
      near-infrared (NIR) region. This coverage is illustrated with MIR and NIR
      absorbance and VCD spectra of 2,2-dimethyl-dioxolane-4-methanol (DDM), alpha
      pinene, and camphor that serve as calibration samples over this entire region.
      Commercially available, dual-source Fourier transform (FT) MIR and NIR VCD
      spectrometers were equipped with appropriate light sources, optics, and
      detectors, and were modified for dual-polarization-modulation (DPM) operation.
      The combination of liquid-nitrogen- and thermoelectric-cooled HgCdTe (MCT)
      detectors, as well as InGaAs and Germanium (Ge) detectors operating at room
      temperature, permitted collection of the desired absorbance and VCD spectra
      across the range of vibrational fundamental, combination band, and overtone
      frequencies. The spectra of DDM and alpha-pinene were measured as neat liquids
      and recorded for both enantiomers in the various spectral regions. Spectra for
      camphor were all measured in CCl(4) solution at a concentration of 0.6 M, except
      for the carbonyl-stretching region, where a more dilute concentration was used.
      The typical anisotropy ratios (g) of the three molecules were estimated with
      respect to their strongest VCD bands in each spectral region. It was found that
      for all three molecules in the spectral regions above 2000 cm(-1), anisotropy
      ratios are approximately the same order (10(-5)) of magnitude. However, in the
      MIR region, the typical anisotropy ratios are significantly different for the
      three molecules. This study demonstrates that with modern FT-VCD spectrometers
      modified for DPM operation, VCD spectra can be measured continuously across a
      wide spectral range from the MIR to nearly the visible region with an unsurpassed
      combination of signal-to-noise ratio and spectral resolution.

PMID- 15479523
TI  - Effects of nonlinearities and uncorrelated or correlated errors in realistic
      simulated data on the prediction abilities of augmented classical least squares
      and partial least squares.
AB  - Comparisons of prediction models from the new augmented classical least squares
      (ACLS) and partial least squares (PLS) multivariate spectral analysis methods
      were conducted using simulated data containing deviations from the idealized
      model. The simulated data were based on pure spectral components derived from
      real near-infrared spectra of multicomponent dilute aqueous solutions. Simulated
      uncorrelated concentration errors, uncorrelated and correlated spectral noise,
      and nonlinear spectral responses were included to evaluate the methods on
      situations representative of experimental data. The statistical significance of
      differences in prediction ability was evaluated using the Wilcoxon signed rank
      test. The prediction differences were found to be dependent on the type of noise
      added, the numbers of calibration samples, and the component being predicted. For
      analyses applied to simulated spectra with noise-free nonlinear response, PLS was
      shown to be statistically superior to ACLS for most of the cases. With added
      uncorrelated spectral noise, both methods performed comparably. Using 50
      calibration samples with simulated correlated spectral noise, PLS showed an
      advantage in 3 out of 9 cases, but the advantage dropped to 1 out of 9 cases with
      25 calibration samples. For cases with different noise distributions between
      calibration and validation, ACLS predictions were statistically better than PLS
      for two of the four components. Also, when experimentally derived correlated
      spectral error was added, ACLS gave better predictions that were statistically
      significant in 15 out of 24 cases simulated. On data sets with nonuniform noise,
      neither method was statistically better, although ACLS usually had smaller
      standard errors of prediction (SEPs). The varying results emphasize the need to
      use realistic simulations when making comparisons between various multivariate
      calibration methods. Even when the differences between the standard error of
      predictions were statistically significant, in most cases the differences in SEP
      were small. This study demonstrated that unlike CLS, ACLS is competitive with PLS
      in modeling nonlinearities in spectra without knowledge of all the component
      concentrations. This competitiveness is important when maintaining and
      transferring models for system drift, spectrometer differences, and unmodeled
      components, since ACLS models can be rapidly updated during prediction when used
      in conjunction with the prediction augmented classical least squares (PACLS)
      method, while PLS requires full recalibration.

PMID- 15479525
TI  - Vibrational spectroscopic study on the origin of stress oscillation during step
      wise stretching in poly(ethylene terephthalate).
AB  - The origin of the phenomenon of stress oscillation during step-wise stretching at
      room temperature for amorphous poly(ethylene terephthalate) (PET) was
      investigated using vibrational spectroscopy. For the first time, transmission
      Fourier transform infrared (FT-IR), attenuated total reflection (ATR) FT-IR, and
      micro-Raman spectroscopies were used in order to investigate the correlation of
      the orientation of the molecular chains, their conformational transformations,
      and the appearance of stress-induced crystallization to the phenomenon of stress
      oscillation during the step-wise stretching procedure. The phenomenon of stress
      oscillation occurs when amorphous PET is exposed to mechanical stress during
      which the extension rate is increased in a step-wise manner. This phenomenon
      leads to the formation of a pattern of opaque and transparent stripes
      (''striated'' or oscillating region), clearly distinguished from the unstretched
      (''bulk'') and the ''necking'' regions. Both infrared and Raman spectroscopic
      investigations revealed that the main conformational transformations and a
      significant increase of the crystallinity occur simultaneously in the
      ''striated'' region. Polarized infrared experiments showed the presence of
      increased molecular orientation, which is more profound for the ''intense
      striated'' region. Finally, micro-Raman spectroscopy allowed the study of opaque
      and transparent stripes individually and showed that the opaque stripes are more
      crystalline. Thus, our findings provide conclusive experimental support for the
      theory, which directly correlates the appearance of the stress-oscillation
      phenomenon with the induction of crystallinity and heat release and is based on
      Barenblatt's model. Our study also provides new conformational assignments for
      the infrared bands in PET for the high-frequency region from 3200 to 3800 cm(-1).
      Specifically, the bands at 3336 cm(-1) and at 3298 cm(-1) have been attributed to
      the trans and gauche conformations, respectively.

PMID- 15479524
TI  - Application of generalized two-dimensional infrared correlation spectroscopy to
      the study of a hydrogen-bonded blend.
AB  - In the preceding studies in this series, generalized two-dimensional (2D)
      infrared correlation spectroscopy has been applied to the study of polymer blends
      with relatively weak intermolecular interactions. In this paper, a miscible
      system with strong intermolecular interactions, hydrogen-bonded blends of poly(4
      vinyl phenol) (PVPh) and poly(methyl methacrylate) (PMMA), is considered. It has
      been found that band positions in 2D plots are dependent on the data sets used,
      due to large peak shifts and/or bandwidth changes. This observation complements
      our preceding studies, in which it was found that new features correspond to
      maxima, minima, or points of inflection in the difference spectra used to
      generate the 2D plots and are not normal modes of vibration of specific
      functional groups. Great care needs to be taken in order not to interpret
      artifacts of the procedure in terms of new spectroscopic features.

PMID- 15479526
TI  - pH-dependent photophysical behavior of rhenium complexes containing
      hydroxypyridine ligands.
AB  - Data related to the pH-dependent photophysics of a class of rhenium complexes
      containing the hydroxypyridine ligand are presented. Data include ground-state
      pK(a) values, emission energies, and lifetimes. The complexes all have ground
      state pK(a) values near 7.0 and exhibit a dramatic change in emission intensity
      near this pH. The lifetimes of these complexes, however, are constant over this
      pH range. A model is presented to account for the observed photophysical
      behavior. The pH-dependent emission properties of these species make them good
      candidates for luminescence-based pH probes, especially in the environmental and
      biomedical fields.

PMID- 15479527
TI  - Minimizing urine autofluorescence under multi-photon excitation conditions.
AB  - We report on the effects of excitation wavelength, laser power, and phase
      resolution on the multi-photon-excited autofluorescence (background) from human
      urine. When compared to the autofluorescence under one-photon excitation
      conditions (lambda(ex) = 260-480 nm), the urine multi-photon-excited
      autofluorescence (lambda(ex) = 725-950 nm) can be less complicated. However, at
      higher laser powers, the multi-photon-excited autofluorescence spectra that are
      produced by excitation above ~775 nm are more complex in comparison to the
      corresponding one-photon-excited autofluorescence. The origin of these more
      complex spectra arises from simultaneous two- and three-photon-driven excitation
      of intrinsic luminescent species within the urine. At lower laser powers, three
      photon-driven processes are minimized and the autofluorescence spectrum is
      simplified. Phase resolution is used to further minimize the urine
      autofluorescence, but it cannot fully eliminate autofluorescence even when
      excitation is performed under multi-photon conditions at 950 nm. For detecting
      250 nM Rhodamine 6G (a mock analyte) dissolved in urine, we find that the two
      photon excitation is superior in comparison to one-photon excitation by 5- to 70
      fold, depending on the excitation wavelength. Phase resolution combined with two
      photon excitation leads to an additional 5- to 7-fold improvement in signal-to
      background ratios in comparison to steady-state two-photon excitation.

PMID- 15479528
TI  - Time-resolved fluorescence microspectroscopy for characterizing crude oils in
      bulk and hydrocarbon-bearing fluid inclusions.
AB  - Time-resolved fluorescence data was collected from a series of 23 bulk crude
      petroleum oils and six microscopic hydrocarbon-bearing fluid inclusions (HCFI).
      The data was collected using a diode laser fluorescence lifetime microscope
      (DLFLM) over the 460-700 nm spectral range using a 405 nm excitation source. The
      correlation between intensity averaged lifetimes (tau) and chemical and physical
      parameters was examined with a view to developing a quantitative model for
      predicting the gross chemical composition of hydrocarbon liquids trapped in HCFI.
      It was found that tau is nonlinearly correlated with the measured polar and
      corrected alkane concentrations and that oils can be classified on this basis.
      However, these correlations all show a large degree of scatter, preventing
      accurate quantitative prediction of gross chemical composition of the oils. Other
      parameters such as API gravity and asphaltene, aromatic, and sulfur
      concentrations do not correlate well with tau measurements. Individual HCFI were
      analyzed using the DLFLM, and time-resolved fluorescence measurements were
      compared with tau data from the bulk oils. This enabled the fluid within the
      inclusions to be classified as either low alkane/high polar or high alkane/low
      polar. Within the high alkane/low polar group, it was possible to clearly
      discriminate HCFI from different locales and to see differences in the trapped
      hydrocarbon fluids from a single geological source. This methodology offers an
      alternative method for classifying the hydrocarbon content of HCFI and observing
      small variations in the trapped fluid composition that is less sensitive to
      fluctuations in the measurement method than fluorescence intensity based methods.

PMID- 15479529
TI  - Pulsed-laser crossed-beam thermal lens spectrometry for detection in a
      microchannel: influence of the size of the excitation beam waist.
AB  - Crossed-beam thermal lens spectrometry is especially designed for the detection
      of very small samples in capillary tubes and more generally in microfluidic
      devices. In this work, the effect of the size of the excitation beam with respect
      to the size of the sample microchannel has been investigated. Although the signal
      is inversely proportional to the size of the excitation waist into the sample,
      the use of large waists may provide greater sensitivities when short-pulse
      excitation lasers are used and allows easier optimization of the optical design.
      On the contrary, the use of small beam waists reduces the edge effects that can
      arise depending on the nature and thickness of the walls of the sample holder.
      Moreover, small beams provide better spatial resolution and have allowed the
      measurement of flow velocities as low as 1 mm s(-1).

PMID- 15479530
TI  - On-line gel permeation chromatography/nuclear magnetic resonance of complex
      polymer formulations.
AB  - Separation of synthetic polymer mixtures by gel permeation chromatography (GPC),
      followed by on-line detection using a 500 MHz nuclear magnetic resonance (NMR)
      spectrometer, has been demonstrated using three different polymer formulations as
      examples. The mobile phase used in all cases was deutero-chloroform, and an
      inexpensive commercially available flow cell was used as a link between the
      separation and detection stages of the experiment. Using this technique it is
      possible to derive chemical information relating to specific molecular sizes of
      polymer mixtures, and not just the size-averaged information that would be
      obtained from standard NMR experiments. This provides an invaluable tool for the
      deformulation of complex mixtures such as those found in the surfactants and
      adhesives industries.

PMID- 15479532
TI  - Surface preparation and direction dependence of diffuse reflectance infrared
      fourier transform spectra of wood.

PMID- 15479531
TI  - Micro-Raman spectroscopy for optical pathology of oral squamous cell carcinoma.
AB  - Micro-Raman spectra of formalin-fixed oral squamous normal and carcinoma tissues,
      stored at room temperature for 2 months, have been recorded. Spectra were
      recorded both in the epithelial and subepithelial regions of the tissues. No
      noticeable spectral contamination due to formalin was observed. Very significant
      differences between spectra of normal epithelial and malignant epithelial samples
      were found. No such differences in spectra of subepithelial malignant and
      subepithelial normal samples could be observed. This study shows that spectra
      from the epithelial region changes drastically because of malignancy-induced
      biochemical changes in this region. Major differences between normal and
      malignant spectra seem to arise from the protein composition,
      conformational/structural changes, and possible increase in protein content in
      malignant epithelia. The differences between normal epithelial and subepithelial
      spectra, as expected, arise mainly from the collagen in subepithelial tissue.
      Principal component analysis of the combined sets of spectra-epithelial and
      subepithelial, normal and malignant- showed that very good discrimination can be
      achieved by Raman microspectroscopy. This study thus validates the suitability of
      formalin-fixed tissues for optical pathology in oral malignancy.

PMID- 15479533
TI  - The underrepresentation of women in science: differential commitment or the queen
      bee syndrome?
AB  - We examined possible explanations for the underrepresentation of women among
      university faculty, in two different national contexts. In the Netherlands, a
      sample of doctoral students (N = 132) revealed no gender differences in work
      commitment or work satisfaction. Faculty members in the same university (N =
      179), however, perceived female students to be less committed to their work and
      female faculty endorsed these gender-stereotypical perceptions most strongly. A
      second study, in Italy, replicated and extended these findings. Again, no gender
      differences were obtained in the self-descriptions of male and female doctoral
      students (N = 80), while especially the female faculty (N = 93) perceived female
      students as less committed to their work than male students. Additional measures
      supported an explanation in social identity terms, according to which individual
      upward mobility (i.e. of female faculty) implies distancing the self from the
      group stereotype which not only involves perceiving the self as a non
      prototypical group member, but may also elicit stereotypical views of other in
      group members.

PMID- 15479534
TI  - Identity construction and British Muslims' political activity: beyond rational
      actor theory.
AB  - Political activity is often addressed in terms of rational actor theory (RAT). We
      review RAT's psychological assumptions and highlight the neglect of collective
      identity. In turn, we view the perception of 'interest' as contingent upon
      constructions of identity and explore how different characterizations of
      collective identity are organized strategically so as to shape people's
      understandings of their interests and how they should act to realize them. Using
      examples taken from a study of British Muslims' political activity we emphasize
      the contested and strategic dimension to identity construction and analyse how
      activists addressing the same constituency construe Muslim identity in different
      ways so as to promote different conceptions of collective interest. Specifically,
      we explore the contested invocations of Prophetic example in the definition of
      Muslim identity. The broader thrust behind this work is a critique of the sharp
      dichotomization of Muslim and non-Muslim political activity. We maintain that
      essentially similar processes of identity construction underlie all attempts to
      organize collective sentiment and political action (including that comprising so
      called 'conventional' electoralist politics in the West), and that conceiving of
      identity as a site of political struggle underscores the inadequacy of
      Orientalist characterizations of Muslim identity in terms of a singular,
      transhistorical essence.

PMID- 15479535
TI  - The fundamental attribution error: a phenomenological critique.
AB  - The fundamental attribution error (Heider, 1958; Ross, 1977) has been extensively
      researched and explanations sought within a social cognitive framework. This work
      is reviewed, and it is noted that there is no unifying theory to account for the
      extensive catalogue of experimental work. Social cognitive explanations have
      proposed distinctions between perceptual, inferential and motivational functions
      within the person to account for the phenomenon. A phenomenological critique of
      this approach is then advanced. Drawing on the thought of Merleau-Ponty (1962) it
      is argued that our understanding of the phenomenon is enhanced by focusing not
      'inside' people, but on interactions between them. In many ways, this brings us
      back to the project of Gestalt psychology, Heider's original framework for
      studying attribution.

PMID- 15479536
TI  - Predictors and predictive effects of ambivalence.
AB  - Recent interest in people's ambivalence about social behaviours and social
      categories has provoked a number of challenges for the ways in which attitudes
      are conceptualized. Research into the implications of ambivalence for attitude
      behaviour relationships and for information processing has developed alongside a
      concern with how best to measure ambivalence and with its implications for the
      application of social psychological theory. In a study (N = 197) of attendance at
      a local health club, two novel issues were addressed: firstly, an assessment of
      the effect of ambivalence on intention-behaviour relationships (using an
      objective behaviour measure) revealed the hypothesized moderation effect;
      secondly, in a move towards identifying some of the factors that may lead to
      ambivalence, an assessment of potential motivational conflicts based on a
      consideration of behavioural beliefs and outcome evaluations was introduced. We
      suggest that this method of assessing ambivalence represents a useful framework
      on which to build a fuller understanding of the relationship between people's
      attitudes and the variety of motives that may influence their social behaviour.
      Pointers for future research are outlined.

PMID- 15479537
TI  - Of bikers, teachers and Germans: groups' diverging views about their
      prototypicality.
AB  - The in-group projection model hypothesizes that members of social groups
      generalize attributes of their in-group to a superordinate category that provides
      dimensions for comparisons between in-group and out-group (in-group projection).
      As a result, both groups in an intergroup situation should disagree about their
      relative prototypicality for the superordinate category. Three studies confirmed
      this prediction. In Study 1 (N = 54), it was found that different groups of motor
      bikers (chopper-bikers vs. sport-bikers) perceived their own subgroup to be the
      more typical biker group than the respective out-group. Study 2 (N = 60) showed
      the same divergence of perspectives in the context of more formal subgroups of
      teachers (primary-school teachers vs. high-school teachers). In a third study (N
      = 157), the relative character of in-group projection was demonstrated in an
      intergroup context with strong reality constraints due to differences in group
      size, status and power. Although there was consensus between both groups that the
      majority (West Germans) was more prototypical of the superordinate group
      (Germans) than the minority (East Germans), majority members perceived the
      groups' difference in prototypicality to be greater than minority members did.

PMID- 15479538
TI  - Death and football: an analysis of men's talk about emotions.
AB  - This study is concerned with men's talk about emotions and with how emotion
      discourses function in the construction and negotiation of masculine ways of
      doing emotions and of consonant masculine subject positions. A sample group of 16
      men, who were recruited from two social contexts in England, participated in
      focus groups on 'men and emotions'. Group discussions were transcribed and
      analysed using discourse analysis. Participants drew upon a range of discursive
      resources in constructing masculine emotional behaviour and negotiating masculine
      subject positions. They constructed men as emotional beings, but only within
      specific, rule-governed contexts, and cited death, a football match and a
      nightclub scenario as prototypical contexts for the permissible/understandable
      expression of grief, joy and anger, respectively. However, in the nightclub
      scenario, the men distanced themselves from the expression of anger as violence,
      whilst maintaining a masculine subject position. These discursive practices are
      discussed in terms of the possibilities for effecting change in men's emotional
      lives.

PMID- 15479539
TI  - False consensus in social context: differential projection and perceived social
      distance.
AB  - The study implicates the notion of perceived social distance as an explanation of
      why ingroup false consensus exceeds outgroup false consensus. Whilst previous
      demonstrations are best understood from social identity perspectives, the
      findings reported here suggest that self-group as well as inter-group comparisons
      can underlie such effects. In particular, perceived social distance was shown to
      mediate the effect of social categorisation: ingroup false consensus was greater
      because more social distance was perceived with the outgroup. The findings also
      extended to non-student samples and generalised across both opinion and ability
      items. In addition, examining the effect of item type in conjunction with social
      categorisation seriously challenged the generality of the false consensus effect.

PMID- 15479540
TI  - Ambivalence and information integration in attitudinal judgment.
AB  - In three studies we investigated the role of bottom-up information processing in
      attitudinal judgment. Overall, the results confirm our expectations and show that
      people are faster in judging attributes underlying their attitude towards the
      object than in generating or 'computing' their overall attitudinal response. As
      predicted, respondents who selected more attributes as important to their
      attitude needed more time to integrate these attributes in order to come to an
      overall attitudinal response. Moreover, ambivalence was also related to decreased
      response times of the overall attitudinal response. We argue that the main reason
      for this is that non-ambivalent attitudes are generally based on evaluatively
      congruent attributes, while ambivalent attitude-holders need to integrate
      evaluatively incongruent attributes into an overall judgment. Implications for
      research on attitude structure and ambivalence are briefly discussed.

PMID- 15479541
TI  - Tri-generational family conversations: communication accommodation and brokering.
AB  - Communication between grandparents and grandchildren can be superficial because
      of insufficient common ground between them. Among Chinese immigrant families in
      New Zealand, communication is complicated by linguistic mismatches, as
      grandparents may be proficient only in Chinese and grandchildren in English. To
      surmount these communication barriers, middle-aged parents (who know the cultures
      and languages of both grandparents and grandchildren) may play the role of a
      'communication broker' to encourage and assist the two generations to
      conversationally move towards each other. We identified 35 cases (tokens) of
      brokering in 12 New Zealand Chinese families and found, as hypothesized, that
      brokering was significantly overrepresented in moderately (compared to high- or
      low-) acculturated families, and that brokers were mostly middle-aged parents. In
      the qualitative part of the study, detailed turn-by-turn analyses of brokering
      were conducted to reveal how brokering was occasioned, its subsequent enactment
      and eventual outcome. The results extend the understanding of unmediated
      communication accommodation in dyadic settings to mediated accommodation in group
      settings wherein a third (and sometimes a fourth) person brokers the
      accommodation. The resultant framework of brokered accommodation will be useful
      for research on other group conversations such as those involving a nurse
      brokering between a doctor and a patient.

PMID- 15479542
TI  - Social support and its consequences: 'positive' and 'deficiency' values and their
      implications for support and self-esteem.
AB  - Recent research on social support has suggested that there may be only a weak
      correlation between perceived and received (enacted) support, with the former
      best seen as a stable, personality-like trait. This study investigates the
      relationship between individual values, self-esteem and perceived and received
      support, with samples taken from four nations (the UK, Portugal, Ghana and
      Mozambique). Respondents completed Schwartz's Portrait Values Questionnaire
      (Schwartz, Melech, Lehmann, Burgess, & Harris, 2001) and measures of self-esteem
      and perceived and received support. The values explained more than twice the
      variance for perceived compared with received support, with those scoring high on
      stimulation, hedonism and benevolence, and low on tradition, conformity and
      security, reporting greater perceived support. In path analyses, values
      significantly predicted perceived support and perceived support predicted self
      esteem, but there was no direct relationship between values and self-esteem.
      These findings are discussed in the light of current debates on the role of
      values in the promotion of prosocial behaviour.

PMID- 15479543
TI  - Adaptability and diversity in simulated turn-taking behavior.
AB  - Turn-taking behavior is simulated in a coupled-agents system. Each agent is
      modeled as a mobile robot with two wheels. A recurrent neural network is used to
      produce the motor outputs and to hold the internal dynamics. Agents are developed
      to take turns on a two-dimensional arena by causing the network structures to
      evolve. Turn taking is established using either regular or chaotic behavior of
      the agents. It is found that chaotic turn takers are more sensitive in response
      to inputs from the other agent. Conversely, regular turn takers are comparatively
      robust against noisy inputs, owing to their restricted dynamics. From many
      observations, including turn taking with virtual agents, we claim that there is a
      complementary relationship between robustness and adaptability. Furthermore, by
      investigating the recoupling of agents from different GA generations, we report
      the emergence of a new turn-taking behavior. Potential for synthesizing a new
      form of interaction is another characteristic of chaotic turn takers.

PMID- 15479544
TI  - Extending self-organizing particle systems to problem solving.
AB  - Self-organizing particle systems consist of numerous autonomous, purely reflexive
      agents ("particles") whose collective movements through space are determined
      primarily by local influences they exert upon one another. Inspired by biological
      phenomena (bird flocking, fish schooling, etc.), particle systems have been used
      not only for biological modeling, but also increasingly for applications
      requiring the simulation of collective movements such as computer-generated
      animation. In this research, we take some first steps in extending particle
      systems so that they not only move collectively, but also solve simple problems.
      This is done by giving the individual particles (agents) a rudimentary
      intelligence in the form of a very limited memory and a top-down, goal-directed
      control mechanism that, triggered by appropriate conditions, switches them
      between different behavioral states and thus different movement dynamics. Such
      enhanced particle systems are shown to be able to function effectively in
      performing simulated search-and-collect tasks. Further, computational experiments
      show that collectively moving agent teams are more effective than similar but
      independently moving ones in carrying out such tasks, and that agent teams of
      either type that split off members of the collective to protect previously
      acquired resources are most effective. This work shows that the reflexive agents
      of contemporary particle systems can readily be extended to support goal-directed
      problem solving while retaining their collective movement behaviors. These
      results may prove useful not only for future modeling of animal behavior, but
      also in computer animation, coordinated movement control in robotic teams,
      particle swarm optimization, and computer games.

PMID- 15479545
TI  - Tracking the trajectories of evolution.
AB  - This article proposes a method of visualizing and measuring evolution in
      artificial life simulations. The evolving population of agents is treated as a
      dynamical system. The proposed method is inspired by the notion of trajectory.
      The article provides examples of tracking of trajectories of evolutionary systems
      in the spaces of genotypes, strategies, and some global characteristics.
      Visualization similar to a bifurcation diagram is used to represent results of a
      series of simulations.

PMID- 15479546
TI  - A graph grammar approach to artificial life.
AB  - We present the high-level language of relational growth grammars (RGGs) as a
      formalism designed for the specification of ALife models. RGGs can be seen as an
      extension of the well-known parametric Lindenmayer systems and contain rule
      based, procedural, and object-oriented features. They are defined as rewriting
      systems operating on graphs with the edges coming from a set of user-defined
      relations, whereas the nodes can be associated with objects. We demonstrate their
      ability to represent genes, regulatory networks of metabolites, and
      morphologically structured organisms, as well as developmental aspects of these
      entities, in a common formal framework. Mutation, crossing over, selection, and
      the dynamics of a network of gene regulation can all be represented with simple
      graph rewriting rules. This is demonstrated in some detail on the classical
      example of Dawkins' biomorphs and the ABC model of flower morphogenesis: other
      applications are briefly sketched. An interactive program was implemented,
      enabling the execution of the formalism and the visualization of the results.

PMID- 15479547
TI  - Cooperation in the iterated prisoner's dilemma is learned by operant conditioning
      mechanisms.
AB  - The prisoner's dilemma (PD) is the leading metaphor for the evolution of
      cooperative behavior in populations of selfish agents. Although cooperation in
      the iterated prisoner's dilemma (IPD) has been studied for over twenty years,
      most of this research has been focused on strategies that involve nonlearned
      behavior. Another approach is to suppose that players' selection of the preferred
      reply might be enforced in the same way as feeding animals track the best way to
      feed in changing nonstationary environments. Learning mechanisms such as operant
      conditioning enable animals to acquire relevant characteristics of their
      environment in order to get reinforcements and to avoid punishments. In this
      study, the role of operant conditioning in the learning of cooperation was
      evaluated in the PD. We found that operant mechanisms allow the learning of IPD
      play against other strategies. When random moves are allowed in the game, the
      operant learning model showed low sensitivity. On the basis of this evidence, it
      is suggested that operant learning might be involved in reciprocal altruism.

PMID- 15479548
TI  - The data-and-signals cellular automaton and its application to growing
      structures.
AB  - In a traditional cellular automaton (CA) a cell is implemented by a rule table
      defining its state at the next time step, given its present state and those of
      its neighbors. The cell thus deals only with states. We present a novel CA where
      the cell handles data and signals. The cell is designed as a digital system
      comprising a processing unit and a control unit. This allows the realization of
      various growing structures, including self-replicating loops and biomorphs. We
      also describe the hardware implementation of these structures within our
      electronic wall for bio-inspired applications, the BioWall.

PMID- 15479549
TI  - Experimental animal urine collection: a review.
AB  - Animal urine collection is a vital part of veterinary practice for ascertaining
      animal health and in scientific investigations for assessing the results of
      experimental manipulations. Untainted animal urine collection is very
      challenging, especially with small rodents, and is an almost impossible task
      under conditions of microgravity. The fundamental aspects of urine collection
      are: (1) ease of collection, (2) quality of sample, (3) prevention of
      contamination, (4) severity of procedures used, (5) levels of pain caused to the
      animal and (6) refinement of methods to reduce stress, pain or distress. This
      review addresses the collection of urine for qualitative and quantitative
      purposes from rodents, rabbits, felines, canines, avian species, equines,
      porcines, ungulates and certain non-human primates, with animal welfare in mind.
      Special emphasis has been given to rodents, canines and non-human primates, since
      they are the animals of choice for research purposes. Free catch (voluntary
      voiding), methods with mild intervention, surgical methods, modified restraint,
      cage and special requirement methods have been reviewed here. Efforts need to be
      taken to provide appropriate animal husbandry and to nurture the animals in as
      natural an environment as possible since experimental results obtained from these
      research subjects are, to a great extent, dependent upon their well-being. A
      continuous refinement in the procedures for collecting urine from experimental
      animals will be the most efficient way of proceeding in obtaining pure urine
      specimens for obtaining reliable research data.

PMID- 15479550
TI  - Chronic implantation of transit-time flow probes on the ascending aorta of
      rodents.
AB  - This study describes the implantation of transit-time flow probes on the
      ascending aorta of rats while minimizing the risk of postoperative complications.
      Special emphasis is placed on our new method of rat intubation as well as the
      production of materials necessary for the implantation procedure such as
      endotracheal tubes and heparin bonded vessel catheters. The effects of these
      devices on the response to acute hypoxia were studied in rats following a 5-7 day
      recovery from the implantation procedure. Systemic and microvascular measurements
      were made on instrumented rats (n = 5) and non-instrumented controls (n = 3) that
      were ventilated with 21%, 15%, 10%, 8% and 5% oxygen. Arterial pressure, PO(2),
      lactate, and base deficit were not different between the implanted and control
      animals at any inspired oxygen concentration. Microvascular flow in the primary
      arterioles of the spinotrapezius muscle was also similar between the two groups
      at all inspired oxygen concentrations. We conclude that this novel methodology
      facilitates the measurement of whole body oxygen delivery in resting and
      haemodynamically-stressed rats.

PMID- 15479551
TI  - Thymectomy should be the first choice in the protection of diabetes-prone BB rats
      for breeding purposes.
AB  - Diabetes-prone (DP)-BB rats spontaneously develop diabetes and are widely used as
      an animal model for the study of type 1 diabetes. Since DP-BB rats develop
      diabetes before or at the time of breeding, such rats used for breeding need to
      be protected against diabetes development by the transfer of regulatory T cells
      obtained from diabetes-resistant (DR)-BB rats, by insulin treatment or by
      thymectomy. Thymectomy of juveniles is not commonly used to protect DP-BB rats,
      and we investigated whether breeding with thymectomized DP-BB rats was a
      realistic alternative to the two other methods. No differences in pregnancy
      rates, numbers of pups per litter or growth rates of pups were found. Moreover,
      no differences were found in diabetes development in the offspring. Protection of
      juvenile DP-BB rats by thymectomy is comparable to the other established
      procedures, is simple and safe, and the rats recover well from the procedure.
      Breeding with thymectomized animals will reduce the number of animals needed, and
      it improves the well-being of the animals because it reduces the negative side
      effects associated with the other procedures such as episodes of hypo and
      hyperglycaemia. Therefore, although thymectomy is an invasive procedure, we would
      like to recommend weanling thymectomy as the first choice for the protection of
      DP-BB rats for breeding purposes.

PMID- 15479552
TI  - Short-term effects of a disturbed light-dark cycle and environmental enrichment
      on aggression and stress-related parameters in male mice.
AB  - In the laboratory setting, environmental factors have a major influence on the
      well-being of laboratory animals. The present study shows the importance of a
      semi-natural light-dark cycle. In this experiment one cohort of mice was kept
      with a continuous lighting for one week. After the first week the artificial
      light-dark cycle was 12:12 with lights on at 07:00 h. The second cohort of mice
      was kept with this 12:12 h light-dark cycle from the start. Half of each cohort
      received environmental enrichment. In order to analyse corticosterone levels,
      urine samples were collected. To measure agonistic behaviour, the behaviour of
      the mice was recorded on videotape immediately after cage cleaning. A significant
      difference in corticosterone levels between cohorts was found during disturbed
      lighting, but not after lighting conditions were reset to 12:12 h. In the first
      test week, mice subjected to disturbed lighting also showed a significantly
      shorter agonistic latency than control mice. This difference had disappeared when
      in the second test week all mice experienced 12:12 h lighting. No effects of
      enriched housing were found. This experiment has shown that disturbed lighting
      for socially-housed male mice caused physiological and behavioural changes
      indicative of stress, not only leading to much higher levels of corticosterone
      but also to shorter agonistic latency within the groups.

PMID- 15479553
TI  - The use of sodium lamps to brightly illuminate mouse houses during their dark
      phases.
AB  - The human and murine diurnal rhythms are out of phase. Consequently in
      conventionally-lit mouse houses the mice's deep sleep is often disrupted, the
      daily welfare monitoring of the mice is limited by their inactivity, and
      scientific data obtained from the mice model the sleeping rather than awake
      human. Sodium light is bichromatic, with both wavelengths being in the human
      visual field but at the margin of murine vision. We report here that sodium lamps
      can be used to light mouse houses to a level that is comfortable for humans, but
      still sufficiently dull to permit nocturnal behaviour in mice. The response of
      mice to sodium light was initially monitored by recording the locomotory activity
      of BALB/c mice. The movement of mice in their cages greatly increased at the
      start of the nocturnal phase. Alterations in the white light cycle caused an
      acute change in the onset of nocturnal behaviour. In contrast, sodium light did
      not suppress the onset of nocturnal locomotory behaviour, even though the
      lighting was sufficiently bright for humans to read without light adaptation. The
      sodium lighting was then used to observe the nocturnal behaviour of over 150 mice
      of various strains, for over 1.5 years. Mice were invariably awake and alert
      during the nocturnal/sodium light phase. All exhibited high locomotory activity,
      except for nursing mothers. Some tasks, such as cage cleaning and minor surgery,
      were more easily done under white than sodium lighting. We therefore adjusted the
      timing of the light cycles to provide white light in the morning and sodium light
      (nocturnal phase) in the afternoon. This provided for easy operation of the mouse
      house, while yielding both animal welfare and scientific advantages.

PMID- 15479554
TI  - Novel restraint system for neuroendocrine studies of socially living common
      marmoset monkeys.
AB  - We describe a novel soft jacket and sling-harness restraint that permits species
      typical postures for small-bodied primates, such as the common marmoset
      (Callithrix jacchus), during long-term (>6 h), continuous restraint. The
      restraint system is straightforward to use and manipulate, it is easily repaired,
      and the materials used are readily available. The soft jacket allows for
      increased versatility and longevity, and the sling-harness provides for greater
      movement and much longer duration of continuous restraint (up to 3 days) compared
      to a previously described, more conventional chair restraint for small-bodied
      primates. The new restraint system prevents the normal diurnal decrease in plasma
      cortisol levels across the daylight hours; however, it does not disrupt ovulatory
      cycles. Unlike the previously available techniques, therefore, this new restraint
      system is applicable to many neurobiological and neuroendocrine studies involving
      small-bodied, non-human primates and is especially suited to investigations
      requiring the maintenance of relationships within social groups.

PMID- 15479555
TI  - Polymorphic microsatellite markers in the outbred CFW and ICR stocks for the
      generation of speed congenic mice on C57BL/6 background.
AB  - Reliable definition of the phenotype of particular alleles is carried out in the
      genetic background of inbred strains. Appearance of mutations in outbred mice
      therefore requires the generation of congenic mice. The aim of this study was the
      establishment of a list of polymorphic microsatellite markers which can be used
      in a polymerase chain reaction (PCR)-based marker-assisted selection protocol
      (MASP) to allow the use of the two common outbred stocks, CFW and ICR, as donor
      animals for the fast generation of congenic C57BL/6 mice. The selection of
      informative microsatellite markers was carried out to provide a simple evaluation
      of the PCR products by conventional agarose gel electrophoresis. Outbred mice
      from three suppliers were examined. In total, 153 microsatellite loci were
      analysed. Here we present 76 and 70 microsatellite markers polymorphic for the
      outbred ICR and CFW stocks compared to C57BL/6. At least three microsatellite
      loci per chromosome were chosen as informative markers for the autosomal genome,
      giving rise to a maximum marker distance of 58 cM. Thus, additional individual
      markers have to be selected for the respective outbred mouse which is chosen as a
      donor animal.

PMID- 15479556
TI  - Non-invasive method for sampling and extraction of mouse DNA for PCR.
AB  - We adapted a non-invasive, fast, reliable and inexpensive procedure for the
      sampling and extraction of deoxyribonucleic acid (DNA) for genetic testing of
      mice. The procedure is based on a simple DNA extraction procedure used in the
      forensic genetic testing of humans. It involves mouth swabbing of the inner cheek
      using a cotton stick, followed by alkaline lysis of the harvested buccal
      epithelial cells. This procedure allows for repeated sampling and genetic testing
      of the individual mouse, and it is faster, simpler and, in our hands, more
      reliable than the currently used routine procedures for the sampling and
      extraction of mouse DNA. Current procedures all involve biopsy of a piece of the
      tail, ear or toe, followed by lengthy procedures to release and isolate the DNA.

PMID- 15479557
TI  - A model for acute iron overload in sea bass (Dicentrarchus labrax L.).
AB  - Evaluation of several parameters involved in iron metabolism was carried out
      after intraperitoneal (i.p.) injection with iron dextran (IDx) in sea bass
      (Dicentrarchus labrax L.). After treatment, a rapid mobilization of IDx from the
      peritoneal cavity to other organs was observed. This was followed by a
      modification of normal peripheral blood iron parameters. Total iron (TI) and
      transferrin saturation (TS) rose rapidly, to 4.14 microg/ml and 83.7%,
      respectively, on day 3. In contrast, unsaturated iron binding capacity (UIBC)
      dropped from 3.19 microg/ml (at day 0) to 0.90 microg/ml on day 3. Tissue iron
      content was determined by atomic absorption spectometry (AAS). Three days post
      IDx injection, values of iron concentration in liver, spleen and head kidney were
      significantly higher than control values (15, 6 and 9-fold increase,
      respectively). Samples of liver, spleen and head kidney were processed for
      routine histology, and the Perl's method was used for iron staining. Histological
      sections of the IDx-treated animals showed iron deposition in all tissues
      studied. In the liver, the iron was evenly distributed over the whole organ,
      being present in the hepatocytes. In the head kidney and spleen, the iron
      deposition was mainly observed in the melanomacrophage centres (MMCs). The
      present study characterizes several parameters involved in iron metabolism, and
      develops a fish model, of iron overload, which can be used in further studies of
      iron toxicity and iron-induced susceptibility to bacterial infections.

PMID- 15479558
TI  - WKY/Ztm-ter: a new rat inbred strain on the WKY/Ztm genetic background with
      congenital teratomas.
AB  - We describe a new rat model for teratomas (WKY/Ztm-ter) which arose through a
      spontaneous mutation in the inbred WKY/Ztm rat strain. When the tumours of the
      gonads became clinically apparent, affected males were 14 to 224 days of age,
      whereas the females only developed tumours between days 21 and 63. Tumour
      incidence is not gender-dependent. However, almost all females develop bilateral
      tumours, while 50% of the males show unilateral tumours. Histologically, all
      examined tumours (n = 65) represent partially undifferentiated teratocarcinomas.

PMID- 15479559
TI  - A natural asymptomatic herpes B virus infection in a colony of laboratory brown
      capuchin monkeys (Cebus apella).
AB  - Herpes B virus (BV) infection of macaques persists in the natural host, but is
      mainly asymptomatic. However, BV can cause fatal disease in humans and in several
      non-macaque species such as capuchin monkeys (Cebus apella). The BV infection
      described here in a colony of capuchin monkeys was persistent but asymptomatic.
      Initially the infection was detected serologically in five out of seven animals.
      However, using polymerase chain reaction (PCR) developed specifically for BV, we
      found the virus in all seven clinically healthy animals. It is probable that the
      infection was transferred from BV-infected macaques housed in different cages but
      in the same room for several years. We have no evidence to indicate that similar
      asymptomatic infections may occur in other New World species but the possibility
      should not be discounted. We recommend that the housing of capuchin monkeys in
      close proximity to macaques should be avoided and that greater caution should be
      used when handling capuchin monkeys and possibly other New World species that
      have been in contact with macaques. All may act as a source of BV infection in
      humans, hence routine, repeated testing of all primates is essential.

PMID- 15479560
TI  - Diurnal variation and age-related changes of bone turnover markers in female
      Gottingen minipigs.
AB  - We investigated diurnal variation and age-related changes in bone turnover
      markers in female Gottingen minipigs. Ten females, 6-9 months of age, were used
      for confirmation of diurnal variation. Blood was collected at 3 h intervals for
      24 h, and bone-specific alkaline phosphatase and intact osteocalcin (OC) levels
      were determined by enzyme immunoassay and radioimmunoassay, respectively. Urine
      was collected at 3 h intervals for 24 h using a tray attached to the bottom of
      the cage. The levels of N-terminal telopeptide of type I collagen (NTX) were
      determined by enzyme immunoassay. Pyridinoline and deoxypyridinoline were
      measured by high performance liquid chromatography. OC and NTX exhibited diurnal
      variation (Kruskal-Wallis test, P < 0.05), with the highest and lowest levels at
      18:00 h (76.7 +/- 26.2 ng/ml) and 06:00 h (44.3 +/- 10.3 ng/ml), and at 03:00
      05:59 h (550.4 +/- 82.4 nmol/micromol Cr) and 12:00-14:59 h (297.8 +/- 152.5
      nmol/micromol Cr), respectively. In the study of age-related changes, blood and
      urine samples from 66 females (age range, 3-76 months) were examined to determine
      the bone turnover markers. All markers showed high correlations with age (0.569 <
      R(2) < 0.818). High levels of bone turnover markers were observed in young
      animals, decreasing with age (Kruskal-Wallis test, P < 0.01). The diurnal
      variation and age-related changes revealed in the present study will be useful in
      studies of bone diseases using female Gottingen minipigs.

PMID- 15479561
TI  - Bioactive carotenoids: potent antioxidants and regulators of gene expression.
AB  - Carotenoids are plant pigments, some of which act as a vital source of vitamin A
      to all animals, that appear to have additional benefits to primates. They are
      potent antioxidants and photoprotectants and can additionally modulate gene
      activity resulting in protection from experimentally-induced inflammatory damage
      and neoplastic transformation. Anti-neoplastic properties appear tightly
      correlated to their ability to induce the gap junctional protein connexin 43
      (Cx43). This when upregulated leads to decreased proliferation and decreased
      indices of neoplasia in animal and human cells. Delivery of natural carotenoids
      can be compromised by poor bioavailability. To overcome this, a synthetic water
      dispersible derivative of astaxanthin has been synthesized and shown to be:
      highly bioavailable; a potent antioxidant; protective against experimental
      ischemia-reperfusion injury and capable of inducing Cx43, suggesting
      antineoplastic potential. The ability to deliver biologically active carotenoids
      at high concentration and with good reproducibility appears to have been
      achieved.

PMID- 15479562
TI  - Effect of fish and fish oil-derived omega-3 fatty acids on lipid oxidation.
AB  - There is evidence that omega-3 (omega3) fatty acids derived from fish and fish
      oils reduce the risk of cardiovascular disease via mechanisms underlying
      atherosclerosis, thrombosis and inflammation. Despite these benefits, there has
      been concern that these fatty acids may increase lipid peroxidation. However, the
      in vivo data to date are inconclusive, due in part to limitations in the
      methodologies. In this regard, our findings using the measurement of F(2)
      isoprostanes, a reliable measure of in vivo lipid peroxidation and oxidant
      stress, do not support adverse effects of omega3 fatty acids on lipid
      peroxidation.

PMID- 15479563
TI  - Effect of reverse micelles on the Rose Bengal-sensitized photo-oxidation of 1-
      and 2-hydroxynaphthalenes.
AB  - Benzylhexadecyl dimethylammonium chloride (BHDC) and sodium bis(2-ethylhexyl)
      sulfosuccinate (AOT) water-in-oil micro-emulsions were employed to study the
      influence of medium heterogeneity on singlet molecular oxygen [O(2)((1)Delta(g))]
      mediated degradation of 1-hydroxynaphthalene (1-OHN) and 2-hydroxynaphthalene (2
      OHN) in their naphthoate form. The kinetic study in the micellar system, that was
      considered as a closer model for the environment of contaminants in natural
      polluted waters, consisted of a comparative work with the process in homogeneous
      solution, by varying surfactant structure and water content of the micro
      emulsion. While it is known that 1-OHN and 2-OHN are rapidly and efficiently
      photo-oxidised in aqueous medium, time-resolved phosphorescence detection of
      O(2)((1)Delta(g)) and stationary photolysis experiments demonstrate that both the
      values for the overall and reactive rate constants for the quenching of
      O(2)((1)Delta(g)) and the photo-oxidation efficiencies are lowered in BHDC
      micelles, whereas the photo-oxidative process in AOT micro-emulsions was totally
      inhibited. Results are interpreted and discussed on the basis of different
      locations of the probe in the micellar environment.

PMID- 15479564
TI  - Effects of PPARgamma ligands and C/EBPbeta enhancer on expression of
      extracellular-superoxide dismutase.
AB  - Extracellular-superoxide dismutase (EC-SOD) is the major SOD isozyme in the blood
      vessel walls and may be important for antioxidant capability of the vascular
      walls. Expression of EC-SOD is known to be regulated by numerous substances such
      as cytokines and vasoactive factors. Recently, we found that the plasma EC-SOD
      levels in type 2 diabetic patients were significantly and inversely related to
      indices of insulin resistance, whereas they were strongly and positively related
      to adiponectin. Administration of pioglitazone significantly increased the plasma
      level of EC-SOD and adiponectin. Transcription factors such as CCAAT/enhancer
      binding proteins (C/EBPs) and peroxisome proliferator-activated receptors (PPARs)
      are known to regulate genes associated with insulin resistance. The aim of this
      study was to assess the contribution of these transcription factors on the EC-SOD
      level. We found that a C/EBPbeta enhancer, prolactin, significantly induced the
      EC-SOD mRNA and protein levels in cultured fibroblast cell lines, but PPARgamma
      ligands, pioglitazone and other thiazolidinedione agents did not. Deletion
      analysis of the EC-SOD promoter-luciferase construct showed that an important
      element responsible for prolactin is located between -242 and -178 in the
      promoter region of the EC-SOD gene in which a known C/EBPbeta-binding site is
      located. Increasing the EC-SOD expression by treatment with ligands of
      transcription factors might be one approach to ameliorate the pathological
      conditions of insulin resistance.

PMID- 15479565
TI  - Reducing power: the measure of antioxidant activities of reductant compounds?
AB  - Electrochemical assay has been employed recently to study the activity of
      antioxidants; however, there is controversy as to whether reducing power fully
      characterizes the antioxidant activity. This study provides some essential
      further evidence on this point based on the reported data and mechanisms
      underlying the antioxidant functions as well as the anodic oxidation of phenolic
      antioxidants, indicating that further consideration and investigation should be
      made before reducing power is used as the absolute measure of antioxidant
      activity.

PMID- 15479566
TI  - Antioxidant properties of Plumbago zeylanica, an Indian medicinal plant and its
      active ingredient, plumbagin.
AB  - Plumbago zeylanica (known as "Chitrak") is a useful Indian medicinal plant. The
      root of the plant and its constituents are credited with potential therapeutic
      properties including anti-atherogenic, cardiotonic, hepatoprotective and
      neuroprotective properties. To examine possible mechanisms of action of P.
      zeylanica (Chitrak), in relation to its reported beneficial properties,
      antioxidant effects of the aqueous/alcoholic extracts of root, corresponding to
      medicinal preparations, and the active ingredient, plumbagin, were studied.
      Methods used included: ferric reducing/antioxidant power (FRAP), radical
      scavenging of 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-azobis-3
      ethylbenzthiazoline-6-sulfonic acid (ABTS), lipid peroxidation in rat liver
      mitochondria induced by different agents, and estimating phenolic and flavonoid
      content. In FRAP/DPPH assays, boiled ethanolic extracts were the most effective,
      while in the ABTS assay boiled aqueous extracts were the most efficient. These
      extracts also significantly inhibited lipid peroxidation induced by cumene
      hydroperoxide, ascorbate-Fe(2+) and peroxynitrite and contained high amounts of
      polyphenols and flavonoids. To examine the mechanisms of action in detail,
      antioxidant and pulse radiolysis studies with plumbagin were conducted. The
      hydroxyl (.OH), alkyl peroxyl (CCl(3)OO.), linoleic acid peroxyl (LOO.), and
      glutathiyl (GS.) radicals generate a phenoxyl radical upon reaction with
      plumbagin. The bimolecular rate constants were: .OH, 2.03 x 10(9) dm(3)mol(-1)s(
      1); CCl(3)OO., 1.1 x 10(9) dm(3)mol(-1)s(-1); LOO., 6.7 x 10(7) dm(3)mol(-1)s(
      1); and GS., 8.8 x 10(8) dm(3)mol(-1)s(-1). In conclusion, our studies reveal
      that extracts of P. zeylanica and its active ingredient plumbagin have
      significant antioxidant abilities that may possibly explain some of the reported
      therapeutic effects.

PMID- 15479567
TI  - Quinolinic acid induces NMDA receptor-mediated lipid peroxidation in rat brain
      microvessels.
AB  - Quinolinic acid increased the generation of lipid peroxidation products by
      isolated rat brain microvessels in vitro. The effect was inhibited both by a
      specific NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid and by
      reduced glutathione (GSH). Furthermore, quinolinic acid displaced specific
      binding of [(3)H]-L-glutamate by cerebral microvessel membranes, particularly in
      the presence of NMDA receptor co-agonist (glycine) and modulator (spermidine). We
      conclude that quinolinic acid can cause potentially cytotoxic lipid peroxidation
      in brain microvessels via an NMDA receptor mediated mechanism.

PMID- 15479569
TI  - The use of CRP for diagnosing infections in young infants < 3 months of age in
      developing countries.
AB  - The diagnosis of severe bacterial infection in young infants in developing
      countries is difficult because of the lack of sensitivity and specificity of the
      presenting symptoms and signs. Whether C-reactive protein (CRP) might help with
      the early detection of neonatal sepsis was investigated in a prospective study in
      The Gambia, Ethiopia and The Philippines. Infants < 3 months of age with symptoms
      or signs of possible sepsis were evaluated; CRP was measured and assessed for its
      ability to predict proven invasive bacterial infection. Of 966 children < 3
      months of age, 54 had a positive blood culture, 13 a positive CSF culture, 15 a
      positive blood and CSF culture and 884 had negative cultures. Median
      (interquartile range) CRP values were 42 (9-173), 14 (6-36), 209 (135-286) and 8
      (3-27) mg/L in the four groups, respectively. Taking a CRP cut-off of 10 mg/L,
      the sensitivity and specificity of an elevated CRP to predict a positive blood or
      CSF culture were 77% and 55%, respectively, and 55% and 82%, respectively, for a
      cut-off of 40 mg/L. CRP lacks the sensitivity and specificity to be used alone as
      a predictor of serious infections in young infants.

PMID- 15479570
TI  - Respiratory syncytial virus and metapneumovirus in children over two seasons with
      a high incidence of respiratory infections in Brazil.
AB  - Acute respiratory infections (ARI) are one of the most important causes of death
      in children. Human metapneumovirus (HMPV), a virus first described in 2001, has
      now been detected in almost all continents. HMPV causes bronchiolitis and
      pneumonia with a clinical spectrum similar to respiratory syncytial virus (RSV).
      We describe the incidence of HMPV and RSV during two consecutive seasons with a
      high incidence of ARI in Aracaju, Brazil. HMPV was responsible for 24% of cases
      of bronchiolitis in the 1st season (April-May 2002) but was not found in the 2nd
      year (April-May 2003). RSV was recovered from 61 (55%) children with ARI in 2002
      and from 72 (68%) in 2003. Children with RSV bronchiolitis in 2002 had more
      hypoxia but less wheezing than in 2003. The incidence of HMPV and RSV genotypes
      causing bronchiolitis varied between the years. Long-term prospective studies are
      required to better describe the epidemiology of these viruses in children.

PMID- 15479571
TI  - Epidemiology and clinical presentation of respiratory syncytial virus infection
      in a Tunisian neonatal unit from 2000 to 2002.
AB  - Respiratory syncytial virus (RSV) is an important viral pathogen causing lower
      respiratory tract infection (LRI) in infants. This study describes the clinical
      and genetic epidemiology of RSV infection among Tunisian neonates. Nasopharyngeal
      aspirates collected from 268 newborns with LRI were screened for RSV by
      immunofluorescence assay. Positive samples were analysed by RT-PCR-hybridisation
      assay for subgroup classification of RSV genomes. RSV infection was present in
      23.1% of neonates, with a predominance in males. Peak incidence occurred in
      winter. Subgroup classification showed a higher prevalence of group B than group
      A strains. Nosocomially acquired RSV infection was present in 37% of neonates,
      54.3% had an underlying condition predisposing to severe disease and 13% died.
      The average duration of hospital stay was 10 days and 87% of newborns required
      supplemental oxygen. As no currently effective treatment is available, preventive
      measures are a priority in high-risk infants.

PMID- 15479572
TI  - Pneumocystis carinii in children with severe pneumonia at Mulago Hospital,
      Uganda.
AB  - The prevalence of Pneumocystis carinii pneumonia (PCP), its clinical and
      radiological features and the outcome in 121 children aged 2-60 months presenting
      with severe pneumonia over a 2-month period at Mulago Hospital, Kampala are
      described. Children presenting with severe pneumonia had sputum induction using
      3% hypertonic saline. The sputum was stained using PCP monoclonal antibodies and
      viewed with fluorescent microscopy. Twenty children with confirmed PCP were
      compared with 101 without PCP. The prevalence of PCP was 16.5%, and 12 (60%) were
      < 6 months of age. Eighteen (42%) of 43 children infected with HIV had PCP and
      two of 78 not infected with HIV. The outcome in children with PCP was poor with a
      case fatality rate of 40% compared with 20% in those without HIV. Radiological
      findings were non-specific. Clinical features associated with PCP included: HIV
      positive infants with a small head circumference, AIDS, a clear chest on
      auscultation and elevated LDH levels. PCP occurs in one in six children < 5 years
      with severe pneumonia in Mulago Hospital. In developing countries where
      investigations for PCP are not routinely available, infants suspected of PCP
      should be treated as an emergency.

PMID- 15479573
TI  - Neonatal chemical hypothyroidism in Nigeria.
AB  - To investigate the level of neonatal chemical hypothyroidism (NCH), thyroid
      function was measured in the cord blood of 271 neonates in an area with a high
      prevalence of endemic goitre, Bassa (n = 140), and a nonendemic area, Jos (n =
      131), in Plateau State, Nigeria. NCH was defined as T4 < 40 nmol/L and TSH > 49
      mU/L and borderline compensated NCH as T4 31-50 nmol/L and TSH 41-49 mU/L. NCH
      was detected in 16.4% of neonates in Bassa and in 3.8% in Jos. Borderline
      compensated NCH was detected in an additional 18.6% in Bassa and 8.4% in Jos.
      Contamination of foodstuffs and water by iodine-containing antiseptics and
      disinfectants during the antenatal period, in addition to factors responsible for
      endemic goitre, e.g. iodine deficiency and goitrogens, are considered to be
      responsible for the high prevalence of NCH in the Bassa area. As most infants'
      thyroid function recovers with time, the former might be a more important factor
      in the aetiology of NCH.

PMID- 15479574
TI  - Systemic lupus erythematosus in Trinidadian children.
AB  - Thirty-three children with a diagnosis of systemic lupus erythematosus (SLE) were
      studied. At diagnosis, 29 of them (88%) were aged between 10 and 17 years and the
      other four (12%) between 5 and 9 years. The majority were girls (28, 82%) and the
      male:female ratio was 1:6.6. Children of East Indian and mixed racial origin
      formed the largest groups (37 and 39%, respectively) and mortality was higher in
      these two groups. The most common symptoms at diagnosis were: fever for > 1 week
      (75.8%), musculoskeletal symptoms (arthralgia, arthritis and myalgia (69.7%) and
      renal involvement (63.6%). Malar and discoid rashes were common, 39 and 37%,
      respectively. Central nervous system involvement at presentation was a rare but
      important cause of mortality. The mortality rate during follow-up was high at
      39.3% and the commonest cause of death was renal failure. Childhood SLE is
      uncommon in Trinidad and Tobago. Diagnosis is often delayed because of the
      protean and non-specific manifestations. This study reports a higher prevalence,
      a more severe course and greater mortality in children of East Indian and mixed
      descent than in children of African origin. It also shows that the symptomatology
      at first presentation is consistent with other studies and should be recognised
      early. Early diagnosis and prompt and appropriate management are essential in
      order to reduce the high mortality still associated with SLE.

PMID- 15479575
TI  - A comparison of kangaroo mother care and conventional incubator care for thermal
      regulation of infants < 2000 g in Nigeria using continuous ambulatory temperature
      monitoring.
AB  - Although skin-to-skin contact (or kangaroo mother care, KMC) for preterm infants
      is a practical alternative to incubator care, no studies have compared these
      methods using continuous ambulatory temperature monitoring. To compare thermal
      regulation in low birthweight infants (< 2000 g) managed by KMC alternating with
      conventional care (CC) and to determine the acceptability to mothers of KMC, an
      experimental study with a crossover design with observational and qualitative
      data collected on temperature patterns and mothers attitudes to skin-to-skin care
      was conducted in the neonatal wards of three hospitals in Lagos, Nigeria.
      Thirteen eligible infants were nursed by their mothers or surrogates in 38 4-hour
      sessions of KMC and the results compared with 38 sessions of incubator care. The
      risk of hypothermia was reduced by > 90% when nursed by KMC rather than
      conventional care, relative risk (RR) 0.09 (0.03-0.25). More cases of
      hyperthermia (> 37.5 degrees C) occurred with KMC, and coreperiphery temperature
      differences were widened, but the risk of hyperthermia > 37.9 degrees C (RR 1.3,
      0.9-1.7) was not significant. Micro-ambient temperatures were higher during KMC,
      although the average room temperatures during both procedures did not differ
      significantly. Mothers felt that KMC was safe, and preferred the method to CC
      because it did not separate them from their infants, although some had problems
      adjusting to this method of care. Where equipment for thermal regulation is
      lacking or unreliable, KMC is a preferable method for managing stable low
      birthweight infants.

PMID- 15479576
TI  - Multi-resistant viridans streptococcal pneumonia and sepsis in the ventilated
      newborn.
AB  - Mechanical ventilation increases the frequency of nosocomial infections. This
      study describes the frequency of multi-resistant viridans streptococcal
      colonisation, the clinical course of nosocomial sepsis and ventilator-associated
      pneumonia in mechanically ventilated neonates in the neonatal intensive care unit
      of Ankara University Hospital. Seventy-nine ventilated newborns were enrolled.
      Broncho-alveolar lavage culture and blood cultures were positive in 44 (56%) and
      17 (22%) patients, respectively. The most predominant micro-organisms in broncho
      alveolar lavage cultures were multi-resistant viridans streptococci (29, 66%).
      Viridans streptococci were also one of the predominant organisms in blood
      cultures (5/17, 29%). In 29 patients with broncho-alveolar lavage positive for
      viridans streptococci, nine (31%) had colonisation, 15 (52%) had ventilator
      associated pneumonia and five (17%) had sepsis owing to viridans streptococcus.
      Ventilator-associated pneumonia was encountered in 52/1000 ventilation days.
      Mortality was caused by infection in three (10%) of them. Mechanically ventilated
      neonates in our neonatal intensive care unit had a high rate of both multi
      resistant viridans streptococcus airway colonisation and subsequent ventilator
      associated pneumonia and sepsis.

PMID- 15479577
TI  - Experience with NTBC therapy in hereditary tyrosinaemia type I: an alternative to
      liver transplantation.
AB  - We present the clinical data of five infants with type I (hepato-renal)
      tyrosinaemia on NTBC therapy. All presented initially at the local hospital in
      the 1st year of life with progressive abdominal distension owing to hepato
      splenomegaly and with radiological evidence of liver cirrhosis, except for one
      child who was diagnosed during screening because of an affected sibling. Age at
      commencement of NTBC therapy ranged from 6 to 30 months. All infants showed
      remarkable improvement within 2-6 months of starting NTBC treatment, except one
      who died 2 months after commencement of therapy from uncontrolled liver failure,
      severe coagulopathy and Streptococcus pneumoniae septicaemia. NTBC treatment
      along with a phenylalanine- and tyrosine-restricted diet has effectively reversed
      most clinical manifestations of this disease. To date, none of our patients has
      developed hepatic carcinoma and NTBC was well tolerated without side-effects.
      NTBC is costly but life-saving and is an obvious alternative to more hazardous
      liver transplantation.

PMID- 15479578
TI  - Fulminant amoebiasis in a child with recurrent multiple amoebic liver abscesses
      and pleuropulmonary complications.
AB  - A 5-year-old boy with recurrent liver abscesses and pleural empyema, presumed to
      be amoebic, is described. Despite surgical drainage of the liver and thoracic
      wall combined with metronidazole and chloroquine, he died 7 weeks after
      admission.

PMID- 15479579
TI  - Deep venous thrombosis and pulmonary embolism following chickenpox.
AB  - An 11-year-old girl developed proximal deep venous thrombosis and bilateral
      pulmonary embolism associated with antiphospholipid syndrome following
      chickenpox. She responded to prolonged anticoagulation therapy.

PMID- 15479580
TI  - Detection of human metapneumovirus in two Tunisian children.

PMID- 15479581
TI  - Dual HIV-1 and HIV-2 infection in a West African infant.

PMID- 15479582
TI  - Gastric stimulation: a new paradigm for management of morbid obesity.

PMID- 15479583
TI  - Applications of electrical pacing in the body.
AB  - Gastric electrostimulation by a pulse generator is an area of intense interest
      for the treatment of obesity. The concept of a rhythmic electrical current
      applied to neural or myal tissues has been established for the treatment of major
      problems in many areas of the body or is being investigated.

PMID- 15479584
TI  - Implantable Gastric Stimulation - the surgical procedure: combining safety with
      simplicity.
AB  - Implantable Gastric Stimulation is a safe and minimally invasive surgical therapy
      currently under investigation for the treatment for severe obesity. Over 500
      patients have been implanted internationally, and thus far, there have been no
      major complications or mortalities. While this technology is proving to be the
      least morbid of the bariatric surgical procedures, it still has the potential to
      result in devastating complications because of the high-risk nature of operating
      on severely obese patients. Keeping the risk of a complication to a minimum
      requires careful attention to preoperative patient preparation, good operative
      technique, and comprehensive perioperative patient care. In addition, like for
      all bariatric procedures, the program must have the appropriate equipment and
      resources to serve this unique patient population. This review will highlight the
      most significant aspects of each issue.

PMID- 15479585
TI  - Long-term follow-up of gastric stimulation for obesity: the Mestre 8-year
      experience.
AB  - BACKGROUND: 10 years experience with gastric stimulation demonstrates promise, in
      particular because weight loss is achieved and maintained without drugs or side
      effects. We report on a total of 65 patients who have received an Implantable
      Gastric Stimulator (IGS(R)) since 1995. METHODS: 65 patients have received an IGS
      and were monitored for weight loss as well as co-morbidities. Gastroesophageal
      Reflux Disease (GERD) was assessed by endoscopy and symptoms were evaluated. An
      acute Holter study was performed on 4 patients pre-implant, post-implant, and
      post-activation of the IGS. Oral glucose tolerance test (OGTT) using a 76-g bolus
      of oral dextrose was done before device implantation and after-activation.
      Gastric emptying was tested on 19 of the patients using Tc99, both pre-implant
      and 6 months post-implant. Resting Energy Expenditure (REE) was studied in 15
      patients using indirect calorimetry at 3 different points in time: pre
      activation, 6 months post-implant, and 12 months post-implant. Blood pressure was
      measured using an electronic wrist device to overcome potential artifacts due to
      arm fat. RESULTS: IGS patients lost significant weight with no side-effects and
      experienced significant and rapid improvements in blood pressure. Almost all of
      the GERD patients reported symptomatic relief during gastric pacing. OGTT
      demonstrated improved response to insulin at 7 months post-stimulation. The
      gastric emptying and REE tests were less conclusive, to a great extent because of
      the small sub-population of patients. CONCLUSION: While the exact mechanisms of
      gastric stimulation remain incompletely understood, it appears that the
      implantation of an IGS is associated with weight loss, an improvement (decrease)
      in blood pressure in hypertensive patients, and a reduction or elimination of
      symptoms in those who had GERD. This promising weight loss therapy warrants
      further study, in particular because of its intriguing results with co
      morbidities.

PMID- 15479586
TI  - Gastric pacing is not enough: additional measures for an effective obesity
      treatment program.
AB  - Obesity has long been considered a behavioral disorder. Recent breakthroughs in
      our understanding of body weight regulation, however, have shown that once
      adipose tissue accumulates, a system of overlapping neuroendocrine systems
      actively resists weight loss. This counter-regulatory mechanism, which has
      evolved as protection against starvation, causes changes in appetite and
      metabolism that limit the amount of weight lost with every obesity intervention,
      including surgery. Future therapies for obesity will focus on neutralizing the
      counter-regulatory mechanisms in a coordinated manner, making greater weight
      losses possible. At this point, gastric stimulation appears to play a role in
      suppressing the compensatory mechanisms of the gut. Thus, gastric stimulation
      should work best when combined with other treatments such as diet, exercise, and
      behavioral change.

PMID- 15479587
TI  - Mechanisms of action of the implantable gastric stimulator for obesity.
AB  - An implantable gastric stimulator (IGS(R)) has been used for the treatment of
      obesity with promising results. However, possible mechanisms involved with the
      treatment of obesity using an IGS are not well understood. According to recent
      clinical and basic studies, it seems that an IGS reduces appetite and increases
      satiety, attributed to its inhibitory effects on gastric motility and its direct
      effects on the central nervous system and hormones related to satiety and/or
      appetite. It has been indicated that chronic gastric stimulation impairs
      intrinsic gastric myoelectrical activity in the fed state, induces gastric
      distention in the fasting state and inhibits postprandial antral contractions.
      The impairment of gastric myoelectrical activity and contractions is associated
      with impaired digestion and emptying of the stomach, which may lead to early
      satiety and reduced food intake. The induction of gastric distention in the
      fasting state results in activation of stretch receptors, causing satiety. It has
      also been shown that an IGS may have direct regulatory effects on the central
      nervous system and certain hormones. Modulation of neuronal activities and
      release of certain hormones with an IGS may also explain the reduction of
      appetite and the increase of satiety.

PMID- 15479588
TI  - Progress in implantable gastric stimulation: summary of results of the European
      multi-center study.
AB  - BACKGROUND: The Implantable Gastric Stimulator (IGS(R)), a pacemaker-like device,
      has been found to be safe and effective to induce and maintain weight loss. The
      LOSS (Laparoscopic Obesity Stimulation Survey) is a prospective non-randomized
      trial which enrolled 69 patients involving 11 investigator centers in 5 European
      Countries. In 19 patients, ghrelin was analyzed. METHODS: Between January 2002
      and December 2003, 69 patients (F/M 49/20), mean age 41 years (18-65) underwent
      IGS implantation. Mean BMI was 41 (35-57), mean weight 115.0 kg (65-160) and mean
      excess weight (EW) 52 kg (13-89). The IGS was actived 30 days after implantation.
      In a subset of 19 patients studied further, 0, 6, and 12 months appetite and
      satiety score were evaluated and 0 and 6 months ghrelin profile was analyzed.
      RESULTS: The mean +/- standard error %EWL was: 8.6+/-1.8 at 1 month, 15.8+/-2.3
      at 3 months, 17.8+/-2.6 at 6 months, 21.0+/-3.5 at 10 months, and 21.0+/-5.0 at
      15 months. There were no intraoperative surgical or long-term complications. 7
      intra-operative gastric penetrations occurred, observed by gastroscopy, without
      sequelae. 1 patient required a reoperation to remove a retained lead needle. In
      the subset of 19 patients, appetite was reduced and post-prandial and inter
      prandial satiety was increased after IGS implantation. In the 19 patients,
      despite weight reduction, ghrelin did not increase. CONCLUSION: IGS can be
      implanted laparoscopically with minimal perioperative complications. Appetite is
      reduced and satiety is increased after the implantation. Ghrelin levels could be
      one of the mechanisms explaining weight loss and weight maintenance in IGS
      patients. If weight loss is maintained, IGS could be considered a good option for
      selected patients.

PMID- 15479590
TI  - The effect of Roux-en-Y gastric bypass on prescription drug costs.
AB  - BACKGROUND: This study examines the effect of weight loss following laparoscopic
      Roux-en-Y gastric bypass (RYGBP) for morbid obesity on prescription drug costs in
      patients over the age of 54. METHODS: 78 patients aged 55 to 75 who met the
      inclusion criteria were identified in a database of 1,060 morbidly obese patients
      undergoing LRYGBP between March 2001 and March 2003. All prescription drugs and
      dosages were recorded preoperatively and postoperatively at 6 months, 1 year, and
      yearly thereafter. Drug history was obtained from the patient and verified by
      records from referring physicians' offices. The cost of a 30-day supply of each
      drug was obtained from 3 retail sources and averaged. RESULTS: The average pre
      LRYGBP cost of prescription drugs was $368.65 per month per patient. The average
      annualized cost at 6 months after LRYGBP was $119.10 per month (down 68%), at 1
      year $118.67 (down 68%) and at 2 years $104.68 per month (down 72%). CONCLUSIONS:
      Weight loss resulting from LRYGBP significantly reduces obesity-related
      morbidities, resulting in a substantial reduction in medication needs in patients
      over the age of 54. The projected cost savings realized in the 78 patients in
      this study amounts to approximately $240,566.04 annually.

PMID- 15479589
TI  - "What are the yanks doing?" the U.S. experience with implantable gastric
      stimulation (IGS) for the treatment of obesity - update on the ongoing clinical
      trials.
AB  - BACKGROUND: The prevalence of obesity is growing worldwide. Medical therapies are
      often ineffective, and surgical treatments have significant risk. IGS(R) offers a
      novel approach to weight loss that was found to be safe and effective in European
      trials. In the U.S., 2 consecutive trials have been undertaken. METHODS: In 2000,
      a multicenter, prospective, randomized, placebo-controlled trial involving 103
      morbidly obese patients (U.S. O-01) was undertaken. In 2002, a prospective, open
      label trial involving 30 morbidly obese patients was initiated (DIGEST). Patients
      were followed for complications, postoperative untoward events, and weight loss.
      RESULTS: In O-01, there were no significant perioperative complications. However,
      20 patients were found to have had lead dislodgements. At 7 months, there was no
      significant difference in weight loss between the activated and non-activated
      groups. After 29 months, loss of excess weight (EWL) approached 20%. With DIGEST,
      there was 1 operative complication (a lost needle retrieved surgically). There
      were no untoward events or known lead dislodgements. EWL was 23% after only 16
      months follow-up. With the introduction of a preoperative screening algorithm,
      almost 40% EWL was achieved for selected patients in both trials. CONCLUSIONS: In
      the U.S., the IGS system for the treatment of obesity has been shown to be safe.
      Technical improvements and better patient selection resulted in improved weight
      loss. The preliminary results of these trials suggest that IGS may be a suitable
      surgical option for selected patients.

PMID- 15479591
TI  - Determinants of the need for intensive care and prolonged mechanical ventilation
      in patients undergoing bariatric surgery.
AB  - BACKGROUND: Bariatric surgery at the upper extremes of weight can be associated
      with serious postoperative complications. In many cases, these complications will
      require the availability of critical care resources. The purpose of this study is
      to examine factors that increase the likelihood for prolonged postoperative
      intensive care unit (ICU) and extended mechanical ventilation (MV) >24 hours.
      METHODS: A retrospective chart review was conducted of all patients undergoing
      bariatric surgery over a 7-year period at a tertiary care academic institution.
      There were 250 total patients undergoing either vertical banded gastroplasty
      (n=15) or Roux-en-Y gastric bypass (n=235). Age, Gender, BMI, pulmonary co
      morbidity, revisional surgery (previous bariatric operations), and need for
      reoperation for suspected intra-abdominal complications were examined by
      univariate and multivariate analyses. RESULTS: Mean age was 43.6+/-10.6 years and
      mean BMI 56+/-10.6 kg/m2. Pulmonary co-morbidity was present in 123/250 patients
      (49%), 42/250 (17%) had revisional surgery, and 21/250 (8%) required reoperation.
      ICU care was required in 60 patients (24%). By univariate analysis, age >50 yrs
      (P=0.047), male gender (P=0.038), and need for reoperation (P <0.001) were
      associated with need for ICU. By multivariate analysis, BMI >60 kg/m2, odds ratio
      (OR) 2.25, 95% confidence Interval (CI) 1.11-4.60, P=0.04, and need for
      reoperation, OR 39.8, 95% CI 10.41-264.7, P <0.0001, were associated with need
      for ICU. MV >24 hrs was required in 44 patients (18%). By univariate analysis,
      BMI >60 kg/m2 (P=0.013), pulmonary co-morbidity (P=0.014), male gender (P
      =0.029), and reoperation (P <0.0001) were associated with need for MV. By
      multivariate analysis, BMI >60 kg/m2, OR 3.1, 95% CI 1.44-7.13, P=0.005, and need
      for reoperation, OR 22.3, 95% CI 7.4-79.2, P <0.0001, were associated with need
      for MV. CONCLUSIONS: Patients who are male, older (>50 yrs), heavier (BMI >60
      kg/m2), and who have complications requiring reoperation will likely need
      intensive care. Additionally, males, heavier patients (BMI >60 kg/m2), pulmonary
      co-morbidity, and need for reoperation may warrant need for extended MV. Surgeons
      and hospitals should consider this when planning resources for bariatric surgery
      programs.

PMID- 15479592
TI  - Glycemic control in diabetic patients after bariatric surgery.
AB  - BACKGROUND: Morbid obesity is associated with a high prevalence of diabetes
      mellitus, and weight loss is fundamental to improve glycemic control. The aim of
      the present study was to evaluate the impact of weight reduction during the late
      postoperative period (> or = 12 months) after gastric bypass on the glycemic
      control of diabetic patients. METHODS: Fasting glycemia (glucose oxidase) and
      glycohemoglobin A1c (enzymatic fluorescence, reference value: 4-6%) were
      determined before and after surgery. Results were compared by the Student t-test
      for paired samples (P <0.05). RESULTS: 23 women and 8 men with diabetes, with a
      mean follow-up of 27.2 months and a mean age of 42.5 years (30-68), were studied.
      Before surgery, mean +/- SD weight, BMI, excess weight, glycemia and
      glycohemoglobin were 135.9+/-11.6 kg, 51.8+/-6.4 kg/m2, 68.3+/-14.5 kg, 173+/
      71.2 mg/dl, and 7.4+/-1.9%, respectively. After surgery, mean weight, BMI, excess
      weight, percent weight loss, percent excess weight loss, glycemia and
      glycohemoglobin were 89.7+/-8.8 kg, 35+/-4.5 kg/m2, 24.6+/-11.6 kg, 32.6%+/-1.8
      (12.6-46.5%), 64.7+/-18.3%, 98+/-17.3 mg/dl (P <0.01), and 5.4+/-1.0% (P <0.05),
      respectively. Oral anti-diabetic drug and/or insulin treatment was discontinued
      in 89.2% of the patients. After surgery, 90.3% of the patients maintained
      glycohemoglobin A1c levels <7.0%. CONCLUSION: Weight loss led to a significant
      and sustained improvement of glycemic control in these patients submitted to
      bariatric surgery.

PMID- 15479593
TI  - Laparoscopic Roux-En-Y gastric bypass is a safe and effective operation for the
      treatment of morbid obesity in patients older than 55 years.
AB  - BACKGROUND: Bariatric surgery in patients >50 years has been controversial. We
      investigated the safety and efficacy of laparoscopic Roux-en-Y gastric bypass
      (LRYGBP) in patients >55 years of age. METHODS: Prospective data on 71 patients
      (54 females and 17 males) undergoing LRYGBP were reviewed. The patients were
      followed for a mean of 17 months (range 2-35 months). RESULTS: The mean age was
      59 years (range 55-67 years), and the mean preoperative BMI was 50.2 kg/m2 (range
      37-65 kg/m2). There were no conversions to open technique. Mean percent of excess
      weight loss (%EWL) was 20%, 48%, 64% and 67% at 1, 6, 12 and 24 months
      respectively. 89% of patients had at least a 50% EWL at 1 year postoperatively.
      There was a significant decrease in the number of patients requiring medical
      treatment for co-morbidities associated with morbid obesity: diabetes mellitus
      87%, hypertension 70% and sleep apnea 86%. There was no inpatient mortality. 1
      patient died suddenly 2 weeks postoperatively of possible myocardial infarction
      or pulmonary embolism. 16 patients developed 22 complications. The median length
      of hospital stay was 3 days. CONCLUSION: LRYGBP is a safe and well-tolerated
      surgical option for the treatment of morbid obesity in patients >55 years old.
      These patients demonstrate a satisfactory weight loss and resolution of co
      morbidities.

PMID- 15479594
TI  - Calcium metabolism in pre- and postmenopausal morbidly obese women at baseline
      and after laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: The authors evaluated calcium metabolism in obese women, before and
      after menopause, at baseline and at 6 and 12 months after laparoscopic Roux-en-Y
      gastric bypass (LRYGBP). LRYGBP restricts food intake and produces physiological
      changes that may be similar to those after high Billroth II subtotal gastrectomy.
      METHODS: Serum calcium (Ca), phosphate, bone-specific alkaline phosphatase (BSAP)
      and 25-hydroxyvitamin D3 (25-OH D) were measured at baseline and 12 months after
      LRYGBP. Urinary N-telopeptide (u-NTX) was measured at baseline and serum C
      telopeptide (s-CTX) at 6 and 12 months after LRYGBP. Parathormone (PTH) was
      measured at baseline and 6 and 12 months after LRYGBP. Patients were divided into
      2 groups: Group I (n=30) pre-menopausal women aged 18-42 y, and Group II (n=30)
      post-menopausal women aged 40-71 y. Patients with renal, hepatic, metabolic and
      bone disease, smoking women, as well as patients with u-NTX values at baseline
      >67 nMBCE/mMCr were excluded. RESULTS: At baseline, PTH was elevated in 10% of
      patients in each group, correlated positively with BMI, and low serum calcium
      values were found in 30% of Group I and 16.7% of Group II. High values of serum C
      telopetide were seen in Group I at 6 months after surgery and in Group II 12
      months after LRYGBP. Group II showed a greater increase in BSAP at 12 months
      after LRYGBP. 25-OHD decreased in both groups, and a progressive increase in PTH
      was observed. Serum calcium did not change in both groups. CONCLUSION: Calcium
      metabolism is altered in pre- and post-menopausal women following LRYGBP. Calcium
      and vitamin D supplementation is strongly advised in all patients.

PMID- 15479595
TI  - Intraoperative endoscopic test resulting in no postoperative leaks from the
      gastric pouch and gastrojejunal anastomosis in 366 laparoscopic Roux-en-Y gastric
      bypasses.
AB  - BACKGROUND: Postoperative leak from the gastric pouch and the anastomosis are
      leading causes of morbidity and mortality after gastric bypass. Many modalities
      have been emerging to prevent this complication. 326 consecutive laparoscopic
      Roux-en-Y gastric bypasses (LRYGBP) were analyzed in a two-surgeon practice and
      found no incidence of leaks from the gastric pouch (GP) and the gastrojejunal
      anastomosis (GJA) with intraoperative endoscopic testing. METHODS: 328
      consecutive RYGBP performed in antecolic fashion from March 2003 to January 2004
      were analyzed. 326 (99%) were performed laparoscopically. After creating a 15 to
      25 cc gastric pouch, integrity of the GP and GJA was tested for leak under saline
      submersion with endoscopic insufflation and placement of a bowel clamp on the
      intestinal limb distal to the GJA. Suture repair of apparent leak was performed
      if needed. RESULTS: Of 326 consecutive LRYGBP utilizing the endoscopic leak test,
      there was no incidence of leak from the GP or GJA. There was one leak from the
      jejuno-jejunosotmy which was repaired laparoscopically on postoperative day #1.
      There was no incidence of leaks in the 2 open RYGBPs. CONCLUSIONS: Many "leak
      prophylaxis" measures have been emerging to prevent this potentially devastating
      complication. However, checking the GP and GJA with a simple endoscopic test can
      minimize the incidence of leaks after LRYGBP.

PMID- 15479596
TI  - Calorie intake and meal patterns up to 4 years after Roux-en-Y gastric bypass
      surgery.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is the most popular surgical
      treatment for morbid obesity in the U.S.A., producing significant and durable
      weight loss with improvement in co-morbidities. Although a greater number of
      patients are undergoing surgical treatment for obesity, little data are available
      regarding their food intake after surgery. This study was undertaken to evaluate
      the caloric amount, nutrient composition and meal patterns of patients 18 months
      to 4 years after RYGBP. Ethnic differences in food intake were also investigated.
      METHODS: Questionnaires were mailed to 360 patients who had undergone RYGBP at
      least 18 months prior to the onset of the study. RESULTS: Data were available
      from 69 patients, 52% Caucasian, 25% African-American, 23% Hispanic. 30 months
      after surgery, the average daily calorie intake was 1733 +/- 630 kcal (n=68,
      range 624-3486 kcal), with 44% of calories from carbohydrates, 22% from protein
      and 33% from fat. Sugar-sweetened beverages represented 7% of total caloric
      intake. Patients consumed 3 meals and 3 snacks per day on average. Food intake
      from dinner and an evening snack represented 40% of the daily caloric intake.
      Snacks accounted for 37% of the daily intake. Percent excess weight loss (%EWL)
      was 58 +/- 17% and was not different among ethnic groups. However, Hispanics
      reported consuming fewer snacks and fewer calories. %EWL correlated with the
      total daily caloric intake (r= .446, P <0.001). Follow-up attendance was 54% at 1
      year after surgery but fell to 10% at 3 years. Only 77% of patients were taking
      vitamin supplements. CONCLUSION: RYGBP resulted in significant weight loss.
      Caloric intake was quite variable. Long-term follow-up remained low, putting
      patients at risk for metabolic and vitamin deficiencies. The relationship between
      caloric intake and long-term weight changes remains to be studied.

PMID- 15479597
TI  - Body contouring following massive weight loss.
AB  - BACKGROUND: Obesity and its associated medical morbidities carry substantial
      health risk. While massive weight loss allows improvement in health status and
      lifestyle, physical sequelae due to symptomatic skin redundancy still require
      treatment. Areas affected include the arms, breasts, abdomen, back, and thighs.
      After open gastric bypass, patients often have poor abdominal support and
      incisional hernias. To completely address the treatment of patients following
      massive weight loss, body contouring procedures are performed, often in one stage
      and tailored to each patient, to rid the functional and esthetic impairment from
      skin redundancy. METHODS: This retrospective study includes 30 patients treated
      from March 1998 to August 2002 by a single surgeon at an academic hospital.
      Average weight loss had been 71 kg, and average weight and BMI at the time of
      contouring surgery were 98.6 kg and 33 kg/m2 respectively. Procedures included
      abdominal panniculectomy, thighlift, backlift, brachioplasty, mastopexy and
      incisional hernia repair, performed either alone or in combination. RESULTS:
      Average weight of resected tissue was 5.9 kg. Average length of stay was 3 days.
      Complications included seroma, wound breakdown, hematoma requiring surgical
      drainage, and lymphocele after brachioplasty. One patient died of a pulmonary
      embolus within weeks after surgery. CONCLUSION: Patients requiring surgical skin
      excision after massive weight loss for functional and/or esthetic reasons are
      challenging, and require individualized approaches with intensive follow-up.

PMID- 15479598
TI  - Outcome of esophageal function and 24-hour esophageal pH monitoring after
      vertical banded gastroplasty and Roux-en-Y gastric bypass.
AB  - BACKGROUND: One of the co-morbidities frequently associated with morbid obesity
      is gastro-esophageal reflux disease (GERD), present in >50 % of morbidly obese
      individuals. We compared the anti-reflux effect of vertical banded gastroplasty
      (VBG) and Roux-en-Y gastric bypass (RYGBP), and their effect on esophageal
      function. METHODS: 10 patients underwent VBG and 40 patients underwent RYGBP.
      Anthropometric parameters, symptomatology of GERD, esophageal manometry (EM),
      isotopic esophageal emptying (IEE) and 24 hr esophageal pH monitoring were
      recorded in all patients preoperatively, and at 3 months and 1 year
      postoperatively. RESULTS: Preoperatively, there was a high prevalence of GERD,
      symptomatic and pH-metric in both groups (57% and 80% respectively). The
      preoperative values of EM and IEE parameters were within the normal range in most
      patients. After surgery, there was an improvement at 3 months postoperatively in
      both groups. 1 year after surgery, the VBG group presented symptomatic GERD in
      30% and pH-metric reflux in 60% of patients while the RYGBP group presented
      symptomatic GERD and pH-metric reflux in 12.5% and 15% of patients, respectively.
      There was an increase in postoperative sensation of dysphagia in both groups (70%
      VBG, 30% RYGBP) one year after operation. After surgery, differences in all EM
      parameters were minimal, and never reached statistical significance for any group
      (VBG and RYGBP). The IEE showed a significantly higher percentage of esophageal
      retention after surgery, but this retention was always within the normal range.
      Both groups had an improvement in anthropometric parameters, but 1 year after
      surgery the results were significantly better in RYGBP patients (70% excess
      weight loss) than in VBG patients (46% excess weight loss). CONCLUSION: >50% of
      morbidly obese individuals suffer from GERD. We did not find changes in
      esophageal function of morbidly obese patients to explain their gastroesophageal
      reflux preoperatively and postoperatively. EM and IEE studies are not indicated
      as standard preoperative tests, except in patients with significant symptoms of
      gastroesophageal reflux. RYGBP is significantly better than VBG as an anti-reflux
      procedure, and had better weight loss.

PMID- 15479599
TI  - Obesity and gastro-esophageal acid reflux: physiopathological mechanisms and role
      of gastric bariatric surgery.
AB  - BACKGROUND: Controversial findings about the relationships between obesity and
      gastro-esophageal reflux have been reported, as well as about the effects of
      weight loss and bariatric surgery on reflux. The aims of this study were to
      evaluate esophageal motility and gastro-esophageal acid circadian patterns in
      obese patients and to test the effects of vertical banded gastroplasty (VBG) on
      these parameters. METHODS: 14 obese subjects (BMI 36-53 kg/m2), 4 men, 10 women,
      27-61 years old, admitted for elective bariatric surgery, underwent clinical
      evaluation, upper endoscopy, esophageal manometry and gastroesophageal pH
      monitoring. Evaluations were repeated 6 to 12 months after gastric surgery that
      consisted of a VBG (7 patients), accompanied in the other 7 patients with an anti
      reflux procedure (fundoplication). Manometric and pH-metric findings in the obese
      patients were compared with a normal-weight control group before and after the
      two different surgical treatments. RESULTS: Gastro-esophageal reflux was
      significantly more frequent in obese (57.1%) than in control group (7.1%).
      Esophageal motility in obese subjects was not different from controls. After VBG
      alone, we found a reduction in basal lower esophageal sphincter (LES) pressure
      and an increase of acid reflux. When VBG was accompanied by fundoplication, basal
      LES pressure increased and acid reflux frequency decreased. CONCLUSIONS: Obesity
      is associated with gastroesophageal reflux. VBG reduced weight, but not gastro
      esophageal acid reflux. Therefore, in our population, this operation cannot be
      considered as an antireflux procedure.

PMID- 15479600
TI  - Singapore experience in obesity surgery.
AB  - BACKGROUND: The outcome of bariatric surgery has been well documented in large
      series in the West. In Asia, where obesity has been less rampant, such surgery
      has been correspondingly less frequent, and there is a dearth of information on
      bariatric surgery on Asians. METHOD: The outcome of a personal series of 40
      patients who underwent "gastric stapling" and banding from 1987 to 2003 in
      Singapore is analyzed. RESULTS: From 1987 to 1997, 26 patients underwent open
      bariatric surgery (Roux-en-Y gastric bypass 4, vertical banded gastroplasty 22).
      Initial mean BMI was 43.3 kg/m2. At 0.6, 1, 2, 4 and 8 years after surgery, mean
      BMI was 35.2, 31.9, 31.2, 31.1 and 34.1 kg/m2. Mean initial weight was 127.2 kg.
      %EWL was 42.2, 56.2, 56.9, 56.3 and 48.3%. From 1999 to 2003, 14 patients
      underwent adjustable gastric banding, 11 by laparoscopy. Initial mean BMI was
      42.9 kg/m2. At 0.6, 1 and 2 years, mean BMI was 38.9, 36.6, and 32.6 kg/m2. Mean
      initial weight was 122.6 kg. %EWL was 26.6, 38.8 and 59.2%. One patient,
      following perigastric insertion of Lap-Band developed band slippage and gastric
      prolapse requiring removal. Since adopting the newer technique of combined pars
      flaccida and perigastric dissection in the last 6 patients, no band slippage has
      occurred. CONCLUSION: Our results of safety and low operative morbidity as well
      as the pattern and magnitude of weight loss following gastric stapling and
      banding for morbidly obese patients in Singapore appears to be similar to the
      Western experience.

PMID- 15479601
TI  - Outpatient laparoscopic gastric banding: initial experience.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) has usually been
      performed as an inpatient procedure with an average hospital stay of 2-4 days.
      The aim of this study was to assess the feasibility of LAGB as an ambulatory
      procedure in selected patients. METHODS: Potential candidates for ambulatory LAGB
      were recruited from patients consulting for obesity surgery. The main inclusion
      criteria were BMI >35 kg/m2 with co-morbid conditions, living within a reasonable
      distance from the hospital, and adult company at home. The patients were admitted
      at 0700 hours on the day of surgery, underwent laparoscopic placement of a Lap
      Band system and were discharged home that evening. RESULTS: 9 women and 1 man
      underwent outpatient LAGB. Mean age was 36 (range 18-52) years and mean BMI was
      38.4 kg/m2 (range 35.1-43.3). Co-morbidities included functional dyspnea (6),
      osteoarthritis (4), arterial hypertension (4), type 2 diabetes (2) and
      dyslipidemia (1). 7 patients had undergone previous abdominal surgery: cesarean
      section (4), appendectomy (3), cholecystectomy (1) and hysterectomy (1). All
      patients had an American Society of Anesthesiologists (ASA) classification of II.
      The average operating time was 87 minutes (range 65-115). The mean time lapse
      between the end of the operation and discharge from hospital was 9.6 hours. There
      were no readmissions, and no complications were noticed at 1 month
      postoperatively. The patients' satisfaction with the ambulatory LAGB procedure
      was high. CONCLUSION: The present study demonstrates that LAGB for obesity may be
      performed on an ambulatory basis without complications.

PMID- 15479602
TI  - Binge eating and its relationship to outcome after laparoscopic adjustable
      gastric banding.
AB  - BACKGROUND: The aim of this cross-sectional study was to examine short and long
      term eating behavior after laparoscopic adjustable gastric banding (LAGB) and the
      relationship of binge eating with weight and quality of life outcome. METHODS:
      250 patients (221 female, 29 male, mean age 39.6 years, age range 22-61) filled
      out questionnaires to evaluate quality of life and eating behavior: 93 patients
      before LAGB, 48 with a follow-up duration of 8 through 24 months, and 109
      patients 25 through 68 months after LAGB. RESULTS: Compared with patients before
      surgery, patients after surgery, in both follow-up groups, reported less binge
      eating, fat intake, external eating, and more restrained eating and eating self
      efficacy. After surgery, about one-third of the patients showed binge eating
      problems, which were associated with a worse postoperative outcome. CONCLUSION:
      Our results suggest that eating behavior improves both short- and long-term after
      surgery for severe obesity. Although LAGB could be a long-term solution to part
      of preoperatively eating disordered patients, the identification and treatment of
      postoperative binge eating appear critical to promote successful outcome after
      bariatric surgery.

PMID- 15479603
TI  - Physical principles of available adjustable gastric bands: how they work.
AB  - BACKGROUND: Commonly used adjustable gastric bands function on two different
      physical principles: low pressure-high volume and high pressure-low volume
      system. METHODS: A study was carried out to investigate the theoretical and
      clinical levels of adjustable band volume-pressure features and their possible
      influence on band-related complications. The theoretical study had two
      objectives: to define physical principles of impact of the band balloon on the
      gastric wall at the stoma region, and to apply a physical formula for calculating
      this data. The objectives of the clinical part of the study were to construct a
      simple reliable measuring device, enabling data collection on an out-patient
      basis from patients who had undergone gastric banding with the two band systems,
      to support or refute the theoretically calculated results. RESULTS: A physical
      formula calculated the pressure applied by the different band systems on the
      gastric wall in the stoma region. Calculations revealed a >100% difference in
      pressure caused by the respective bands. Invasive pressure measurements in 35
      patients with the different balloon systems agreed with the calculated data, and
      found a >100% difference in pressure affecting the stoma wall both at rest and
      during meals. CONCLUSIONS: Differences in pressure on the gastric wall related to
      the physical system on which the bands operate may be a partial explanation for
      long-term complications of respective bands.

PMID- 15479604
TI  - Laparoscopic gastric banding as a universal method for the treatment of patients
      with morbid obesity.
AB  - INTRODUCTION: This study analyzed the influence of potentially negative
      predictors such as sweet-eating behavior, super-obesity, social and psychological
      status, family and education situation, intake of sedative drugs, and the
      distance between hospital and home on the outcome of laparoscopic adjustable
      gastric banding (LAGB). METHODS: 77 women and 29 men with mean age 40.6 years (28
      47) underwent LAGB. Preoperative mean body weight was 146 kg (99-179), and mean
      BMI was 48.1 kg/m2 (36.4-73.5). The influence of the above-mentioned potentially
      negative predictors on weight loss was the primary end point. RESULTS: Mean
      follow-up was 44.6 +/- 19.7 months. Follow-up was possible in all but 6 patients.
      Median excess weight loss (EWL) was 52.1% (range 28.6-72.2%). Univariate analysis
      revealed no influence of the investigated negative predictors on the weight
      reduction. Median EWL in 24 sweet-eater patients was 55.6% compared to 55.4% in
      82 non-sweet-eaters (P=0.65). A significant difference in the weight reduction
      was found between super-obese and non-superobese groups (P <0.001). CONCLUSIONS:
      LAGB should be recommended without limitation as the operation of choice for
      morbidly obese patients. Gastric bypass operations should be recommended only in
      cases of unsuccessful LAGB.

PMID- 15479605
TI  - Post-surgery group therapy for gastric bypass patients.
AB  - BACKGROUND: The prevalence of both compulsive eating patterns (bingeing and
      "grazing") and psychosocial distress and/or psychiatric co-morbidity in patients
      seeking bariatric surgery has been documented. While surgery is often seen as the
      solution, research has shown that these problems can persist postoperatively and
      may adversely affect outcome. This paper will describe a postoperative
      psychotherapy group process designed specifically for gastric bypass patients.
      METHODS: A semi-structured cognitive-behavioral group therapy program adapted
      from a treatment program for compulsive eaters was designed for patients who had
      been identified (by questionnaire and clinical interview) as having compulsive
      eating problems before surgery. Therapy addresses eating patterns as well as the
      emotional adjustments following surgery. RESULTS: 16 12-week therapy groups have
      been conducted to date. The groups are small and designed to help patients
      understand the stages of postoperative adjustment and the tasks, both eating
      related and psychological, associated with each stage. Feedback from participants
      has been very positive with patients reporting the need for a therapy group in
      addition to the traditional support group. CONCLUSION: Since both disturbed
      eating patterns and psychological difficulties are seen following surgery, it is
      imperative that treatment programs be developed to address these issues. The
      group process is a highly effective intervention but must be designed for the
      special needs of these patients. Measures of success need to take psycho-social
      factors into account as well as eating behaviors and weight loss. Outcome studies
      are needed to compare those receiving treatment vs those who do not.

PMID- 15479606
TI  - Psoriasis remission after laparoscopic Roux-en-Y gastric bypass for morbid
      obesity.
AB  - BACKGROUND: Psoriasis is a chronic skin disease characterized by epithelial
      hyperplasia and an accelerated rate of epithelial turnover affecting
      approximately 1-3% of the population. Exogenous and endogenous factors including
      morbid obesity can increase the morbidity of psoriasis. CASE REPORT: A 55-year
      old male, who weighed 131 kg with BMI 41 kg/m2, underwent laparoscopic Roux-en-Y
      gastric bypass (LRYGBP). He had a 15-year duration of severe psoriasis and was
      being medically treated. At 12 months after LRYGBP, he had lost 39 kg (68% EWL),
      and had complete resolution of the psoriasis and had discontinued all
      preoperative medications related to the disease. At 2 years after LRYGBP,
      psoriasis has not recurred. CONCLUSION: Weight loss after LRYGBP should be
      considered as a strategy in the treatment of severe psoriasis in morbidly obese
      patients.

PMID- 15479607
TI  - Wernicke's encephalopathy after Roux-en-Y gastric bypass.
AB  - Complications of bariatric operations include the development of nutritional
      deficiencies. If protracted vomiting is added, severe vitamin depletion could
      arise such as thiamine deficiency, resulting in the development of Wernicke's
      encephalopathy (WE). This article describes the rapid onset of WE in a 6-week
      postoperative morbidly obese woman. Because the occurrence of micronutrient
      deficiencies is infrequent, although reports are increasing, symptoms may be
      misdiagnosed leading to possible irreversible effects on the central nervous
      system. The importance of a prompt diagnosis of this serious complication and of
      adequate therapy is emphasized.

PMID- 15479609
TI  - Laparoscopic adjustable gastric band: do support groups add to the weight loss?

PMID- 15479610
TI  - Combining gastric banding and biliopancreatic diversion.

PMID- 15479611
TI  - Total intra-abdominal laparoscopic gastric bypass.

PMID- 15479612
TI  - The mitochondrial tricarboxylate carrier of silver eel: chemical modification by
      sulfhydryl reagents.
AB  - The tricarboxylate (or citrate) carrier was purified from eel liver mitochondria
      and functionally reconstituted into liposomes. Incubation of the proteoliposomes
      with various sulfhydryl reagents led to inhibition of the reconstituted citrate
      transport activity. Preincubation of the proteoliposomes with reversible SH
      reagents, such as mercurials and methanethiosulfonates, protected the eel liver
      tricarboxylate carrier against inactivation by the irreversible reagent N-(1
      pyrenyl)maleimide (PM). Citrate and L-malate, two substrates of the
      tricarboxylate carrier, protected the protein against inactivation by sulfhydryl
      reagents and decreased the fluorescent PM bound to the purified protein. These
      results suggest that the eel liver tricarboxylate carrier requires a single
      population of free cysteine(s) in order to manifest catalytic activity. The
      reactive cysteine(s) is most probably located at or near the substrate binding
      site of the carrier protein.

PMID- 15479613
TI  - Combined cytogenetic and molecular analyses for the diagnosis of Prader
      Willi/Angelman syndromes.
AB  - Prader-Willi (PWS) and Angelman (AS) are syndromes of developmental impairment
      that result from the loss of expression of imprinted genes in the paternal (PWS)
      or maternal (AS) 15q11-q13 chromosome. Diagnosis on a clinical basis is difficult
      in newborns and young infants; thus, a suitable molecular test capable of
      revealing chromosomal abnormalities is required. We used a variety of cytogenetic
      and molecular approaches, such as, chromosome G banding, fluorescent in situ
      hybridization, a DNA methylation test, and a set of chromosome 15 DNA
      polymorphisms to characterize a cohort of 27 PWS patients and 24 suspected AS
      patients. Molecular analysis enabled the reliable diagnosis of 14 PWS and 7 AS
      patients, and their classification into four groups: (A) 6 of these 14 PWS
      subjects (44 %) had deletions of paternal 15q11-q13; (B) 4 of the 7 AS patients
      had deletions of maternal 15q11-q13; (C) one PWS patient (8 %) had a maternal
      uniparental disomy (UPD) of chromosome 15; (D) the remaining reliably diagnoses
      of 7 PWS and 3 AS cases showed abnormal methylation patterns of 15q11-q13
      chromosome, but none of the alterations shown by the above groups, although they
      may have harbored deletions undetected by the markers used. This study highlights
      the importance of using a combination of cytogenetic and molecular tests for a
      reliable diagnosis of PWS or AS, and for the identification of genetic
      alterations.

PMID- 15479614
TI  - Construction and differential screening of a cDNA library specific to osmotic
      stress of Haloxylon ammodendron seedlings.
AB  - A subtracted cDNA library specific to osmotic stress of Haloxylon ammodendron
      (Mey.) Bge seedlings was constructed by suppression subtractive hybridization
      (SSH) and T/A cloning. SSH was performed between two groups of H. ammodendron
      seedlings, one was cultivated in Hoagland (H) solution as a driver and the other
      group was treated with osmotic stress of the Hoagland solution by the addition of
      400 mM mannitol (M), as a tester. The library consisted of about 400 recombinant
      clones, with the average size being of 500 bp, ranging from 300 bp to 1500 bp.
      Using a PCR-select differential screening kit, 100 recombinant clones were
      randomly chosen from the subtracted cDNA library and hybridized with forward,
      reverse subtracted and unsubtracted probes for two rounds. As a result, 21
      positive clones specific to osmotic stress were obtained and some of them were
      verified by Northern blot analysis. The sequencing analysis of 6 positive clones
      and the following homology comparison to GenBank [blastx] non-redundant databases
      characterized that two sequences obtained in this experiment may contribute to
      novel drought-related genes.

PMID- 15479615
TI  - Substrate ground state binding energy concentration is realized as transition
      state stabilization in physiological enzyme catalysis.
AB  - Previously published kinetic data on the interactions of seventeen different
      enzymes with their physiological substrates are re-examined in order to
      understand the connection between ground state binding energy and transition
      state stabilization of the enzyme-catalyzed reactions. When the substrate ground
      state binding energies are normalized by the substrate molar volumes, binding of
      the substrate to the enzyme active site may be thought of as an energy
      concentration interaction; that is, binding of the substrate ground state brings
      in a certain concentration of energy. When kinetic data of the enzyme/substrate
      interactions are analyzed from this point of view, the following relationships
      are discovered: 1) smaller substrates possess more binding energy concentrations
      than do larger substrates with the effect dropping off exponentially, 2) larger
      enzymes (relative to substrate size) bind both the ground and transition states
      more tightly than smaller enzymes, and 3) high substrate ground state binding
      energy concentration is associated with greater reaction transition state
      stabilization. It is proposed that these observations are inconsistent with the
      conventional (Haldane) view of enzyme catalysis and are better reconciled with
      the shifting specificity model for enzyme catalysis.

PMID- 15479616
TI  - Isolation and molecular characterization of a new CRT binding factor gene from
      Capsella bursa-pastoris.
AB  - A new CRT binding factor (CBF) gene designated Cbcbf25 was cloned from Capsella
      bursa-pastoris, a wild grass, by the rapid amplification of cDNA ends (RACE). The
      full-length cDNA of Cbcbf25 was 898 bp with a 669 bp open reading frame (ORF)
      encoding a putative DRE/CRT (LTRE)-binding protein of 223 amino acids. The
      predicted CbCBF25 protein contained a potential nuclear localization signal (NLS)
      in its N-terminal region followed by an AP2 DNA-binding motif and a possible
      acidic activation domain in the C-terminal region. Bioinformatic analysis
      revealed that Cbcbf25 has a high level of similarity with other CBF genes like
      cbf1, cbf2, and cbf3 from Arabidopsis thaliana, and Bncbf5, Bncbf7, Bncbf16, and
      Bncbf17 from Brassica napus. A cold acclimation assay showed that Cbcbf25 was
      expressed immediately after cold triggering, but this expression was transient,
      suggesting that it concerns cold acclimation. Our study implies that Cbcbf25 is
      an analogue of other CBF genes and may participate in cold-response, by for
      example, controlling the expression of cold-regulated genes or increasing the
      freezing tolerance of plants.

PMID- 15479617
TI  - Microarrays for the detection of HBV and HDV.
AB  - The increasing pace of development in molecular biology during the last decade
      has had a direct effect on mass testing and diagnostic applications, including
      blood screening. We report the model Microarray that has been developed for
      Hepatitis B virus (HBV) and Hepatitis D virus (HDV) detection. The specific
      primer pairs of PCR were designed using the Primer Premier 5.00 program according
      to the conserved regions of HBV and HDV. PCR fragments were purified and cloned
      into pMD18-T vectors. The recombinant plasmids were extracted from positive
      clones and the target gene fragments were sequenced. The DNA microarray was
      prepared by robotically spotting PCR products onto the surface of glass slides.
      Sequences were aligned, and the results obtained showed that the products of PCR
      amplification were the required specific gene fragments of HBV, and HDV. Samples
      were labeled by Restriction Display PCR (RD-PCR). Gene chip hybridizing signals
      showed that the specificity and sensitivity required for HBV and HDV detection
      were satisfied. Using PCR amplified products to construct gene chips for the
      simultaneous clinical diagnosis of HBV and HDV resulted in a quick, simple, and
      effective method. We conclude that the DNA microarray assay system might be
      useful as a diagnostic technique in the clinical laboratory. Further applications
      of RD-PCR for the sample labeling could speed up microarray multi-virus
      detection.

PMID- 15479618
TI  - Association between the angiotensin-converting enzyme gene insertion/deletion
      polymorphism and essential hypertension in young Pakistani patients.
AB  - Several studies have demonstrated the importance of angiotensin-converting enzyme
      (ACE) insertion (I)/deletion (D) polymorphisms in the pathogenesis of
      hypertension. This study sought to determine the association between the ACE I/D
      polymorphism and essential hypertension in young Pakistanis. The frequency of the
      ACE I/D polymorphism was established by a comparative cross-sectional survey of
      Pakistani patients suffering from essential hypertension and ethnically matched
      normotensive controls. Samples were collected from tertiary care hospitals in
      northern Pakistan. Hypertensive individuals were defined as those with a systolic
      blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg on three
      separate occasions, or those currently receiving one, or more, anti-hypertensive
      agents. DNA samples obtained from hypertensive (n = 211) and normotensive (n =
      108) individuals were typed by PCR. The frequency of the ACE I/I genotype was
      significantly higher in hypertensive patients, aged 20-40 years, than in
      normotensive controls of the same age group (chi(2) = 4.0, P = 0.041). Whereas no
      overall significant differences were observed between the I/I, I/D and D/D ACE
      genotypes (One way ANOVA, F = 0.672; P = 0.413). The association between the ACE
      I/I genotype and essential hypertension in individuals aged </= 40 years suggests
      that ACE has a role in early onset essential hypertension in Pakistan.

PMID- 15479619
TI  - Neutralizing chimeric mouse-human antibodies against Burkholderia pseudomallei
      protease: expression, purification and characterization.
AB  - A recombinant Fab monoclonal antibody (Fab) C37, previously obtained by phage
      display and biopanning of a random antibody fragment library against Burkholderia
      pseudomallei protease, was expressed in different strains of Escherichia coli. E.
      coli strain HB2151 was deemed a more suitable host for Fab expression than other
      E. coli strains when grown in media supplemented with 0.2 % glycerol. The
      expressed Fab fragment was purified by affinity chromatography on a Protein G
      Sepharose column, and the specificity of the recombinant Fab C37 towards B.
      pseudomallei protease was proven by Western blotting, enzyme-linked immunosorbent
      assay (ELISA) and by proteolytic activity neutralization. In addition, polyclonal
      antibodies against B. pseudomallei protease were produced in rabbits immunized
      with the protease. These were isolated from high titer serum by affinity
      chromatography on recombinant-Protein A-Sepharose. Purified polyclonal antibody
      specificity towards B. pseudomallei protease was proven by Western blotting and
      ELISA.

PMID- 15479620
TI  - Solution structure of human orexin-A: regulator of appetite and wakefulness.
AB  - Orexin-A and orexin-B (hypocretin-1 and hypocretin-2, respectively) are important
      hypothalamic neuro-peptides, which are encoded by a single mRNA transcript and
      stimulate food intake as well as regulate wakefulness. Here we determined the
      solution structure of orexin-A by NMR spectroscopy and by simulated-annealing
      calculation. The structural features of orexin-A involve two alpha-helices, with
      the hydrophobic residues disposed to on one side of helix, and hydrophilic
      residues to the other. A hydrophilic turn induced by two disulfide bonds provides
      the key difference between orexin-A and -B. With previous mutagenic studies, the
      derived structure of orexin-A provides us with a structure-functional view for
      novel drug design.

PMID- 15479621
TI  - Molecular cloning, sequencing, and expression of a fibrinolytic serine-protease
      gene from the earthworm Lumbricus rubellus.
AB  - The full-length cDNA of the lumbrokinase fraction 6 (F6) protease gene of
      Lumbricus rubellus was amplified using an mRNA template, sequenced and expressed
      in E. coli cells. The F6 protease gene consisted of pro- and mature sequences by
      gene sequence analysis, and the protease was translated and modified into active
      mature polypeptide by N-terminal amino acid sequence analysis of the F6 protease.
      The pro-region of F6 protease consisted of the 44 residues from methionine-1 to
      lysine-44, and the mature polypeptide sequence (239 amino acid residues and one
      stop codon; 720 bp) started from isoleucine-45 and continued to the terminal
      residue. F6 protease gene clones having pro-mature sequence and mature sequence
      produced inclusion bodies in E. coli cells. When inclusion bodies were orally
      administrated rats, generated thrombus weight in the rat's venous was reduced by
      approximately 60 % versus controls. When the inclusion bodies were solubilized in
      pepsin and/or trypsin solutions, the solubilized enzymes showed hemolytic
      activity in vitro. It was concluded the F6 protease has hemolytic activity, and
      that it is composed of pro- and mature regions.

PMID- 15479623
TI  - Unfolding of ervatamin C in the presence of organic solvents: sequential
      transitions of the protein in the O-state.
AB  - The folding of ervatamin C was investigated in the presence of various
      fluorinated and non-fluorinated organic solvents. The differences in the
      unfolding of the protein in the presence of various organic solvents and the
      stabilities of O-states were interpreted. At pH 2.0, non-fluorinated alkyl
      alcohols induced a switch from the native alpha-helix to a beta-sheet, contrary
      to the beta-sheet to alpha-helix conversion observed for many proteins. The
      magnitude of ellipticity at 215 nm, used as a measure of beta-content, was found
      to be dependent on the concentration of the alcohol. Under similar conditions of
      pH, fluorinated alcohol enhanced the intrinsic a-helicity of the protein
      molecule, whereas the addition of acetonitrile reduced the helical content.
      Ervatamin C exhibited high stability towards GuHCl induced unfolding in different
      O-states. Whereas the thermal unfolding of O-states was non-cooperative, contrary
      to the cooperativity seen in the absence of the organic solvents under similar
      conditions. Moreover, the differential scanning calorimetry endotherms of the
      protein acquired at pH 2.0 were deconvoluted into two distinct peaks, suggesting
      two cooperative transitions. With increase in pH, the shape of the thermogram
      changed markedly to exhibit a major and a minor transition. The appearance of two
      distinct peaks in the DSC together with the non-cooperative thermal transition of
      the protein in O-states indicates that the molecular structure of ervatamin C
      consists of two domains with different stabilities.

PMID- 15479622
TI  - Genetic polymorphism of glutathione S-transferase P1 and breast cancer risk.
AB  - To evaluate the potential association between the GSTP1 genotype and the
      development of breast cancer, a hospital based case-control study was conducted
      on Korean women. The study population consisted of 171 histologically confirmed
      incident breast cancer cases and 171 age-matched controls with no present or
      previous history of cancer. PCR-RFLP was used for the GSTP1 genotyping and
      statistical evaluations were performed using an unconditional logistic regression
      model. Postmenopausal women with the GSTP1 Val allele were found to have a
      reduced risk of breast cancer (OR = 0.3, 95 % CI = 0.10-0.74). A significant
      interaction was observed between the GSTP1 genotype and alcohol consumption (p
      for interaction = 0.01); compared with never-drinking women with Ile/Ile
      genotype, ever-drinking women with the GSTP1 Val allele had almost a three-fold
      risk of breast cancer (OR = 2.9, 95 % CI = 1.05-7.85), whereas never-drinking
      women with Val allele had half this risk (OR = 0.5, 95 % CI = 0.27-0.93). Our
      findings suggest that the GSTP1 polymorphism influences individual susceptibility
      to breast cancer in the Korean women and this effect may be modified by alcohol
      consumption.

PMID- 15479624
TI  - A mutagenic study of beta-1,4-galactosyltransferases from Neisseria meningitidis.
AB  - N-terminal His-tagged recombinant beta-1,4-galactosyltransferase from Neisseria
      meningitidis was expressed and purified to homogeneity by column chromatography
      using Ni-NTA resin. Mutations were introduced to investigate the roles of, Ser68,
      His69, Glu88, Asp90, and Tyr156, which are components of a highly conserved
      region in recombinant beta-1,4 galactosyltransferase. Also, the functions of
      three other cysteine residues, Cys65, Cys139, and Cys205, were investigated using
      site-directed mutagenesis to determine the location of the disulfide bond and the
      role of the sulfhydryl groups. Purified mutant galactosyltransferases, His69Phe,
      Glu88Gln and Asp90Asn completely shut down wild-type galactosyltransferase
      activity (1-3 %). Also, Ser68Ala showed much lower activity than wild-type
      galactosyltransferase (19 %). However, only the substitution of Tyr156Phe
      resulted in a slight reduction in galactosyltransferase activity (90 %). The
      enzyme was found to remain active when the cysteine residues at positions 139 and
      205 were replaced separately with serine. However, enzyme reactivity was found to
      be markedly reduced when Cys65 was replaced with serine (27 %). These results
      indicate that conserved amino acids such as Cys65, Ser68, His69, Glu88, and Asp90
      may be involved in the binding of substrates or in the catalysis of the
      galactosyltransferase reaction.

PMID- 15479625
TI  - Effects of chlorpromazine HCl on the structural parameters of bovine brain
      membranes.
AB  - Fluorescence probes located in different membrane regions were used to evaluate
      the effects of chlorpromazine .HCl on structural parameters (transbilayer lateral
      mobility, annular lipid fluidity, protein distribution, and lipid bilayer
      thickness) of synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine
      cerebral cortex. The experimental procedure was based on the selective quenching
      of 1,3-di(1-pyrenyl)propane (Py-3-Py) by trinitrophenyl groups, radiationless
      energy transfer from the tryptophan of membrane proteins to Py-3-Py, and energy
      transfer from Py-3-Py monomers to 1-anilinonaphthalene-8-sulfonic acid (ANS). In
      this study, chlorpromazine .HCl decreased the lateral mobility of Py-3-Py in a
      concentration dependent-manner, showed a greater ordering effect on the inner
      monolayer than on the outer monolayer, decreased annular lipid fluidity in a dose
      dependent-manner, and contracted the membrane lipid bilayer. Furthermore, the
      drug was found to have a clustering effect on membrane proteins.

PMID- 15479626
TI  - The gene expression profile of cyst epithelial cells in autosomal dominant
      polycystic kidney disease patients.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder
      characterized by the formation of fluid-filled cysts in the kidney and
      progressive renal failure. Other manifestations of ADPKD include the formation of
      cysts in other organs (liver, pancreas, and spleen), hypertension, cardiac
      defects, and cerebral aneurysms. The loss of function of the polycystin -1 and -2
      results in the formation of epithelium-lined cysts, a process that depends on
      initial epithelial proliferation. cDNA microarrays powerfully monitor gene
      expression and have led to the discoveries of pathways regulating complex
      biological processes. We undertook to profile the gene expression patterns of
      epithelial cells derived from the cysts of ADPKD patients using the cDNA
      microarray technique. Candidate genes that were differently expressed in cyst
      tissues were identified. 19 genes were up-regulated, and 6 down-regulated. Semi
      quantitative RT-PCR results were consistent with the microarray findings. To
      distinguish between normal and epithelial cells, we used the hierarchical method.
      The results obtained may provide a molecular basis for understanding the
      biological meaning of cytogenesis.

PMID- 15479627
TI  - The activities of antioxidant enzymes in response to oxidative stresses and
      hormones in paraquat-tolerant Rehmannia glutinosa plants.
AB  - All members of R. glutinosa show the unique characteristic of intrinsic tolerance
      to paraquat (PQ). Antioxidant enzymes have been proposed to be the primary
      mechanism of PQ resistance in several plant species. Therefore, the antioxidant
      enzyme systems of R. glutinosa were evaluated by comparatively analyzing cellular
      antioxidant enzyme levels, and their responses of oxidative stresses and
      hormones. The levels of ascorbate peroxidase (APX), glutathione reductase (GR),
      non-specific peroxidase (POX), and superoxide dismutase (SOD) were 7.3-, 4.9-,
      2.7- and 1.6-fold higher in PQ-tolerant R. glutinosa than in PQ-susceptible
      soybeans. However, the activity of catalase (CAT) was about 12-fold higher in the
      soybeans. The activities of antioxidant enzymes reduced after PQ treatment in the
      two species, with the exception of POX and SOD in R. glutinosa, which increased
      by about 40 %. Interestingly, the activities of APX, SOD and POX in R. glutinosa,
      relative to those in soybeans, were further increased by 49, 67 and 93 % after PQ
      treatment. The considerably higher intrinsic levels, and increases in the
      relative activities of antioxidant enzymes in R. glutinosa under oxidative stress
      support the possible role of these enzymes in the PQ tolerance of R. glutinosa.
      However, the relatively lower levels of SOD versus PQ tolerance, and the mixed
      responses of antioxidant enzymes to stresses and hormones, suggest a possible
      alternative mechanism(s) for PQ tolerance in R. glutinosa.

PMID- 15479628
TI  - Presence of proboscipedia and caudal gene homologues in a bivalve mollusc.
AB  - Homeobox genes encode a family of transcription factors that have essential roles
      in regulating the development of eukaryotes. Although they have been extensively
      studied in different phyla, relatively little is known about homeoboxcontaining
      genes and their function in molluscs. In this study, we used a polymerase chain
      reaction to investigate homeobox genes in the bivalve mollusc Pecten maximus.
      Four different homeobox sequences were identified; two were homologues of the non
      Hox cluster gene caudal and the two remaining sequences had a significant
      homology to the ANT-C gene Proboscipedia. These sequences represent the first cad
      and pb homologues isolated from a member of the class Bivalvia, phylum Mollusca.

PMID- 15479629
TI  - A continuous spectrophotometric assay for NADPH-cytochrome P450 reductase
      activity using 1,1-diphenyl-2-picrylhydrazyl.
AB  - NADPH-cytochrome P450 reductase (CPR) transfers electrons from NADPH to
      cytochrome P450, and catalyzes the one-electron reduction of many drugs and
      foreign compounds. Various forms of spectrophotometric titration have been
      performed to investigate the electron-accepting properties of CPR, particularly,
      to examine its ability to reduce cytochrome c and ferricyanide. In this study,
      the reduction of 1,1-diphenyl-2-picrylhydrazyl (DPPH) by CPR was assessed as a
      means of monitoring CPR activity. The principle advantage of DPPH is that its
      reduction can be assayed directly in the reaction medium by a continuous
      spectrophotometry. Thus, electrons released from NADPH by CPR were transferred to
      DPPH, and DPPH reduction was then followed spectrophotometrically by measuring
      A(520) reduction. Optimal assay concentrations of DPPH, CPR, potassium phosphate
      buffer, and NADPH were first established. DPPH reduction activity was found to
      depend upon the strength of the buffer used, which was optimal at 100 mM
      potassium phosphate and pH 7.6. The extinction coefficient of DPPH was 4.09mM(-1)
      cm(-1). DPPH reduction followed classical Michaelis-Menten kinetics (K(m) = 28
      microM, k(cat) = 1690 min(-1)). This method uses readily available materials, and
      has the additional advantages of being rapid and inexpensive.

PMID- 15479630
TI  - Translation silenced by fused pair of tRNA synthetases.
AB  - In this issue of Cell, discover gene-specific translational silencing as a novel
      function of the fused glutamyl- and prolyl-tRNA synthetase (GluProRS). GluProRS
      is released from a multisynthetase translation complex in response to gamma
      interferon and forms a four-protein GAIT complex that silences translation of
      ceruloplasmin (Cp), a protein linked to the inflammatory response.

PMID- 15479631
TI  - Like poles repel; molecular mechanisms of dendritic tiling.
AB  - To cover the entire sensory field once and only once, dendrites of some sensory
      system neurons avoid crossing other dendrites from the same type of neurons. In
      this issue of Cell, provide first insight into the molecular mechanisms of
      dendritic tiling.

PMID- 15479632
TI  - A nuclear strike against Listeria--the evolving life of LXR.
AB  - LXRs are members of the nuclear receptor superfamily and function as master
      regulators of cholesterol metabolism. In the macrophage, they control cholesterol
      efflux and inhibit the transcription factor NF-kappaB-mediated proinflammatory
      responses. In this issue of Cell, discover surprising, protective functions for
      LXRalpha in innate immunity.

PMID- 15479633
TI  - Spatial positioning; a new dimension in genome function.
AB  - The eukaryotic cell nucleus is a heterogeneous organelle. Chromosomes are
      nonrandomly positioned within the nuclear space, and individual gene loci
      experience distinct local environments due to the presence of chromatin domains
      and subnuclear compartments. Recent observations have highlighted the important
      yet still largely mysterious role of spatial positioning in genome activity and
      stability.

PMID- 15479634
TI  - Biological control through regulated transcriptional coactivators.
AB  - Gene activation in higher eukaryotes requires the concerted action of
      transcription factors and coactivator proteins. Coactivators exist in
      multiprotein complexes that dock on transcription factors and modify chromatin,
      allowing effective transcription to take place. While biological control focused
      at the level of the transcription factor is very common, it is now quite clear
      that a substantial component of gene control is directed at the expression of
      coactivators, involving pathways as diverse as B-cell development, smooth muscle
      differentiation, and hepatic gluconeogenesis. Quantitative control of
      coactivators allows the functional integration of multiple transcription factors
      and facilitates the formation of distinct biological programs. This coordination
      and acceleration of different steps in linked pathways has important kinetic
      considerations, enabling outputs of particular pathways to be increased far more
      than would otherwise be possible. These kinetic aspects suggest opportunities and
      concerns as coactivators become targets of therapeutic intervention.

PMID- 15479635
TI  - Mapping the location of TFIIB within the RNA polymerase II transcription
      preinitiation complex: a model for the structure of the PIC.
AB  - Biochemical probes positioned on the surface of the general transcription factor
      TFIIB were used to probe the architecture of the RNA polymerase II (Pol II)
      transcription preinitiation complex (PIC). In PICs, the TFIIB linker and core
      domains are positioned over the central cleft and wall of Pol II. This
      positioning is not observed in the smaller Pol II-TFIIB complex. These results
      lead to a new model for the structure of the PIC, which agrees with most
      previously documented protein-DNA interactions within Pol II and archaea PICs.
      Specific interaction of the TFIIB core domain with Pol II positions and orients
      the promoter DNA over the Pol II central cleft, and TBP-DNA bending leads to
      bending of the promoter around the surface of Pol II. The TFIIF subunit Tfg1 was
      found in close proximity to the TFIIB B finger, linker, and core domains,
      suggesting that these two factors closely cooperate during initiation.

PMID- 15479636
TI  - Native E2F/RBF complexes contain Myb-interacting proteins and repress
      transcription of developmentally controlled E2F target genes.
AB  - The retinoblastoma tumor suppressor protein (pRb) regulates gene transcription by
      binding E2F transcription factors. pRb can recruit several repressor complexes to
      E2F bound promoters; however, native pRb repressor complexes have not been
      isolated. We have purified E2F/RBF repressor complexes from Drosophila embryo
      extracts and characterized their roles in E2F regulation. These complexes contain
      RBF, E2F, and Myb-interacting proteins that have previously been shown to control
      developmentally regulated patterns of DNA replication in follicle cells. The
      complexes localize to transcriptionally silent sites on polytene chromosomes and
      mediate stable repression of a specific set of E2F targets that have sex- and
      differentiation-specific expression patterns. Strikingly, seven of eight complex
      subunits are structurally and functionally related to C. elegans synMuv class B
      genes, which cooperate to control vulval differentiation in the worm. These
      results reveal an extensive evolutionary conservation of specific pRb repressor
      complexes that physically combine subunits with established roles in the
      regulation of transcription, DNA replication, and chromatin structure.

PMID- 15479637
TI  - Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific silencing
      of translation.
AB  - Aminoacyl tRNA synthetases (ARS) catalyze the ligation of amino acids to cognate
      tRNAs. Chordate ARSs have evolved distinctive features absent from ancestral
      forms, including compartmentalization in a multisynthetase complex (MSC),
      noncatalytic peptide appendages, and ancillary functions unrelated to
      aminoacylation. Here, we show that glutamyl-prolyl-tRNA synthetase (GluProRS), a
      bifunctional ARS of the MSC, has a regulated, noncanonical activity that blocks
      synthesis of a specific protein. GluProRS was identified as a component of the
      interferon (IFN)-gamma-activated inhibitor of translation (GAIT) complex by RNA
      affinity chromatography using the ceruloplasmin (Cp) GAIT element as ligand. In
      response to IFN-gamma, GluProRS is phosphorylated and released from the MSC,
      binds the Cp 3'-untranslated region in an mRNP containing three additional
      proteins, and silences Cp mRNA translation. Thus, GluProRS has divergent
      functions in protein synthesis: in the MSC, its aminoacylation activity supports
      global translation, but translocation of GluProRS to an inflammation-responsive
      mRNP causes gene-specific translational silencing.

PMID- 15479638
TI  - RGS-7 completes a receptor-independent heterotrimeric G protein cycle to
      asymmetrically regulate mitotic spindle positioning in C. elegans.
AB  - Heterotrimeric G proteins promote microtubule forces that position mitotic
      spindles during asymmetric cell division in C. elegans embryos. While all
      previously studied G protein functions require activation by seven-transmembrane
      receptors, this function appears to be receptor independent. We found that
      mutating a regulator of G protein signaling, RGS-7, resulted in hyperasymmetric
      spindle movements due to decreased force on one spindle pole. RGS-7 is localized
      at the cell cortex, and its effects require two redundant Galphao-related G
      proteins and their nonreceptor activators RIC-8 and GPR-1/2. Using recombinant
      proteins, we found that RIC-8 stimulates GTP binding by Galphao and that the RGS
      domain of RGS-7 stimulates GTP hydrolysis by Galphao, demonstrating that Galphao
      passes through the GTP bound state during its activity cycle. While GTPase
      activators typically inactivate G proteins, RGS-7 instead appears to promote G
      protein function asymmetrically in the cell, perhaps acting as a G protein
      effector.

PMID- 15479639
TI  - RIC-8 is required for GPR-1/2-dependent Galpha function during asymmetric
      division of C. elegans embryos.
AB  - Heterotrimeric G proteins are crucial for asymmetric cell division, but the
      mechanisms of signal activation remain poorly understood. Here, we establish that
      the evolutionarily conserved protein RIC-8 is required for proper asymmetric
      division of one-cell stage C. elegans embryos. Spindle severing experiments
      demonstrate that RIC-8 is required for generation of substantial pulling forces
      on astral microtubules. RIC-8 physically interacts with GOA-1 and GPA-16, two
      Galpha subunits that act in a partially redundant manner in one-cell stage
      embryos. RIC-8 preferentially binds to GDP bound GOA-1 and is a guanine
      nucleotide exchange factor (GEF) for GOA-1. Our analysis suggests that RIC-8 acts
      before the GoLoco protein GPR-1/2 in the sequence of events leading to Galpha
      activation. Furthermore, coimmunoprecipitation and in vivo epistasis demonstrate
      that inactivation of the Gbeta subunit GPB-1 alleviates the need for RIC-8 in one
      cell stage embryos. Our findings suggest a mechanism in which RIC-8 favors
      generation of Galpha free from Gbetagamma and enables GPR-1/2 to mediate
      asymmetric cell division.

PMID- 15479640
TI  - Drosophila Dpp morphogen movement is independent of dynamin-mediated endocytosis
      but regulated by the glypican members of heparan sulfate proteoglycans.
AB  - The Drosophila transforming growth factor beta (TGF-beta) homolog Decapentaplegic
      (Dpp) acts as a morphogen that forms a long-range concentration gradient to
      direct the anteroposterior patterning of the wing. Both planar transcytosis
      initiated by Dynamin-mediated endocytosis and extracellular diffusion have been
      proposed for Dpp movement across cells. In this work, we found that Dpp is mainly
      extracellular, and its extracellular gradient coincides with its activity
      gradient. We demonstrate that a blockage of endocytosis by the dynamin mutant
      shibire does not block Dpp movement but rather inhibits Dpp signal transduction,
      suggesting that endocytosis is not essential for Dpp movement but is involved in
      Dpp signaling. Furthermore, we show that Dpp fails to move across cells mutant
      for dally and dally-like (dly), two Drosophila glypican members of heparin
      sulfate proteoglycan (HSPG). Our results support a model in which Dpp moves along
      the cell surface by restricted extracellular diffusion involving the glypicans
      Dally and Dly.

PMID- 15479641
TI  - Control of dendritic branching and tiling by the Tricornered-kinase/Furry
      signaling pathway in Drosophila sensory neurons.
AB  - To cover the receptive field completely but without redundancy, neurons of
      certain functional groups exhibit tiling of their dendrites via dendritic
      repulsion. Here we show that two evolutionarily conserved proteins, the
      Tricornered (Trc) kinase and Furry (Fry), are essential for tiling and branching
      control of Drosophila sensory neuron dendrites. Dendrites of fry and trc mutants
      display excessive terminal branching and fail to avoid homologous dendritic
      branches, resulting in significant overlap of the dendritic fields. Trc control
      of dendritic branching involves regulation of RacGTPase, a pathway distinct from
      the action of Trc in tiling. Timelapse analysis further reveals a specific loss
      of the ability of growing dendrites to turn away from nearby dendritic branches
      in fry mutants, suggestive of a defect in like-repels-like avoidance. Thus, the
      Trc/Fry signaling pathway plays a key role in patterning dendritic fields by
      promoting avoidance between homologous dendrites as well as by limiting dendritic
      branching.

PMID- 15479642
TI  - Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family
      protein, directs GABAergic innervation at purkinje axon initial segment.
AB  - Distinct classes of GABAergic synapses are segregated into subcellular domains
      (i.e., dendrite, soma, and axon initial segment-AIS), thereby differentially
      regulating the input, integration, and output of principal neurons. In
      cerebellum, for example, basket interneurons make exquisitely precise "pinceau
      synapses" on AIS of Purkinje neurons, but the underlying mechanism is unknown.
      Using BAC transgenic reporter mice, we found that basket axons always contacted
      Purkinje soma before innervating AIS. This synapse targeting process followed the
      establishment of a subcellular gradient of neurofascin186 (NF186), an L1 family
      immunoglobulin cell adhesion molecule (L1CAM), along the Purkinje AIS-soma axis.
      This gradient was dependent on ankyrinG, an AIS-restricted membrane adaptor
      protein that recruits NF186. In the absence of neurofascin gradient, basket axons
      lost directional growth along Purkinje neurons and precisely followed NF186 to
      ectopic locations. Disruption of NF186-ankyrinG interactions at AIS reduced
      pinceau synapse formation. These results implicate ankyrin-based localization of
      L1CAMs in subcellular organization of GABAergic synapses.

PMID- 15479643
TI  - Removal of Ca2+ channel beta3 subunit enhances Ca2+ oscillation frequency and
      insulin exocytosis.
AB  - An oscillatory increase in pancreatic beta cell cytoplasmic free Ca2+
      concentration, [Ca2+]i, is a key feature in glucose-induced insulin release. The
      role of the voltage-gated Ca2+ channel beta3 subunit in the molecular regulation
      of these [Ca2+]i oscillations has now been clarified by using beta3 subunit
      deficient beta cells. beta3 knockout mice showed a more efficient glucose
      homeostasis compared to wild-type mice due to increased glucose-stimulated
      insulin secretion. This resulted from an increased glucose-induced [Ca2+]i
      oscillation frequency in beta cells lacking the beta3 subunit, an effect
      accounted for by enhanced formation of inositol 1,4,5-trisphosphate (InsP3) and
      increased Ca2+ mobilization from intracellular stores. Hence, the beta3 subunit
      negatively modulated InsP3-induced Ca2+ release, which is not paralleled by any
      effect on the voltage-gated L type Ca2+ channel. Since the increase in insulin
      release was manifested only at high glucose concentrations, blocking the beta3
      subunit in the beta cell may constitute the basis for a novel diabetes therapy.

PMID- 15479644
TI  - IKKbeta/NF-kappaB activation causes severe muscle wasting in mice.
AB  - Muscle wasting accompanies aging and pathological conditions ranging from cancer,
      cachexia, and diabetes to denervation and immobilization. We show that activation
      of NF-kappaB, through muscle-specific transgenic expression of activated IkappaB
      kinase beta (MIKK), causes profound muscle wasting that resembles clinical
      cachexia. In contrast, no overt phenotype was seen upon muscle-specific
      inhibition of NF-kappaB through expression of IkappaBalpha superrepressor (MISR).
      Muscle loss was due to accelerated protein breakdown through ubiquitin-dependent
      proteolysis. Expression of the E3 ligase MuRF1, a mediator of muscle atrophy, was
      increased in MIKK mice. Pharmacological or genetic inhibition of the IKKbeta/NF
      kappaB/MuRF1 pathway reversed muscle atrophy. Denervation- and tumor-induced
      muscle loss were substantially reduced and survival rates improved by NF-kappaB
      inhibition in MISR mice, consistent with a critical role for NF-kappaB in the
      pathology of muscle wasting and establishing it as an important clinical target
      for the treatment of muscle atrophy.

PMID- 15479645
TI  - LXR-dependent gene expression is important for macrophage survival and the innate
      immune response.
AB  - The liver X receptors (LXRs) are nuclear receptors with established roles in the
      regulation of lipid metabolism. We now show that LXR signaling not only regulates
      macrophage cholesterol metabolism but also impacts antimicrobial responses. Mice
      lacking LXRs are highly susceptible to infection with the intracellular bacteria
      Listeria monocytogenes (LM). Bone marrow transplant studies point to altered
      macrophage function as the major determinant of susceptibility. LXR-null
      macrophages undergo accelerated apoptosis when challenged with LM and exhibit
      defective bacterial clearance in vivo. These defects result, at least in part,
      from loss of regulation of the antiapoptotic factor SPalpha, a direct target for
      regulation by LXRalpha. Expression of LXRalpha or SPalpha in macrophages inhibits
      apoptosis in the setting of LM infection. Our results demonstrate that LXR
      dependent gene expression plays an unexpected role in innate immunity and suggest
      that common nuclear receptor pathways mediate macrophage responses to modified
      lipoproteins and intracellular pathogens.

PMID- 15479646
TI  - An evaluation of the utility of performing body fluid counts on the coulter LH
      750.
AB  - Performing a manual body fluid count is a tedious, time-consuming, and frequently
      imprecise process for any clinical laboratory. The ability to perform many of
      these counts with an automated hematology analyzer has the real potential of
      making a major impact on laboratory precision and productivity. The manual
      chamber count is fraught with many variables and is often very
      technologist/technique dependent, often leading to inaccuracies in test results.
      Our laboratory undertook a series of studies designed to evaluate the capability
      of the Coulter LH 750 hematology analyzer to supplement our current manual method
      in the performance of body fluid analysis. First, we established the performance
      of our current manual counting method, the gold standard against which LH 750
      performance would be judged. We looked at the precision of manual cell counting
      by having 4 technologists perform manual counts on each of 35 spinal, synovial,
      peritoneal, and other fluids with white blood cell (WBC) and/or red blood cell
      (RBC) counts of greater than 0.3 x 10(9) /L and 0.03 x 10(12) /L, respectively.
      Our results support earlier reports that the variability in counts among
      technologists using the manual chamber cell count methods is often very
      significant. After each sample was manually counted, it was analyzed on the
      Coulter LH 750, and the results were compared with those of our current manual
      method. Results showed good correlation between the manual and LH 750 methods.
      Next, we conducted a series of separate tests to evaluate the stability of
      different cellular elements (WBCs and RBCs) in each of these body fluid types.
      The study consisted of 2 sets of 4--3-mL samples of each fluid type--which were
      analyzed on the LH 750 immediately on receipt and after 1 hour, 4 hours, 8 hours,
      16 hours, and 24 hours. The findings suggested varying degrees of stability that
      were dependent on fluid type and initial cell concentration. Finally, we looked
      at whether it is necessary to perform background counts before analyzing each
      body fluid sample and the impact of automating body fluid counts on our workload.

PMID- 15479647
TI  - Unstable plasma thalidomide concentration in patients with refractory multiple
      myeloma.
AB  - In this study, we analyzed the relationship between the plasma concentration of
      thalidomide and the therapeutic effect obtained by using thalidomide alone in
      patients with refractory multiple myeloma. The safety and effect of thalidomide
      was examined in 12 cases of refractory multiple myeloma. Four cases (33%)
      achieved partial response (PR) and 3 cases (25%) achieved minimal response. These
      effects were achieved with only 200 mg/day of thalidomide and maintained with 100
      200 mg/day. The concentration of thalidomide in the blood was measured in 7
      cases; dose-dependency was not recognized. In 5 cases in which complete or
      partial response was obtained, the effect was obtained with a mean thalidomide
      concentration in blood of 0.5 microg/mL or less. However, in 2 cases in which the
      mean blood concentration of thalidomide was 2 microg/mL or higher, an M-protein
      reducing effect was not obtained. The frequency of various side effects was
      increased when the concentration of thalidomide was higher than 2 microg/mL. In
      conclusion, low-dose thalidomide therapy may effectively treat refractory
      myeloma, and the measurement of thalidomide concentration in the blood may not be
      a marker of therapeutic effect, but rather a marker of adverse effects.

PMID- 15479648
TI  - Avoiding regression analysis pitfalls when calibrating white blood cell
      differential counters.
AB  - Method comparison and calibration are important for clinical hematologists and
      for manufacturers of new methods and instruments. Automation of the white blood
      cell (WBC) differential count poses unique problems in this regard because the
      reference method is a microscopic manual cell count of 200 WBCs. A highly
      variable reference method can obscure the true relation between the reference and
      the test methods and reduce sensitivity to miscalibration. A computer model based
      on published cell distributions and on the statistical properties of proportions
      was created to enable testing of alternative approaches to calibration. Ordinary
      linear regression (OLR) and standard Deming regression (SDR) were applied to a
      comparison of the results obtained with a virtual cell counter (counting 2,000
      WBCs) and that obtained with a virtual 200-cell reference method for monocytes
      (mean population percentage of 7.1%) and lymphocytes (mean population percentage
      of 29%). Both regression approaches can misrepresent the known mathematical
      relation between the methods. This problem almost always occurs when OLR is used
      and the proportion of the cell of interest is low, as in the case of monocytes
      (7.1% of the total count). OLR comparisons, however, introduce significant error
      even for cell counts of 29%. SDR performed much better for both cell types.

PMID- 15479650
TI  - Proceedings of the XVIIth International Symposium on Technological Innovations in
      Laboratory Hematology. May 13-15, 2004. Barcelona, Spain.

PMID- 15479649
TI  - An optimized method for the assay of the red blood cell--age-related enzyme
      aspartate aminotransferase.
AB  - Three methods of preparation of red blood cell concentrate for erythrocyte
      aspartate aminotransferase measurement were compared: (1) filtration of whole
      blood through a cellulose column (n = 36); (2) washing of whole blood and
      aspiration of buffy coat after centrifugation (n = 48); (3) optimized method with
      washing without aspiration of buffy coat (n = 229).

PMID- 15479651
TI  - Comparison of the KKU-DCIP diagnostic kit to the standard hemoglobin
      electrophoresis method for detection of hemoglobin E carriers.

PMID- 15479652
TI  - A note on the mean corpuscular volume in hemoglobin E carriers.

PMID- 15479654
TI  - Exclusive breastfeeding: isn't some breastfeeding good enough?

PMID- 15479655
TI  - A test in leadership: eliminating "group think" in your organization.

PMID- 15479656
TI  - Response to the Merewood/Heining commentary published in the May 2004 issue.

PMID- 15479657
TI  - Differential response to breastfeeding peer counseling within a low-income,
      predominantly Latina population.
AB  - This study aims to identify those most responsive to breastfeeding peer
      counseling (PC) using data from a US-based randomized trial. The authors ran a
      series of logistic regression models to identify differential responses to PC,
      using breastfeeding status at 0, 1, 3, and 6 months postpartum as the dependent
      variables. Three subgroups were found to be most responsive to breastfeeding PC.
      Multiparae receiving PC were 6 times more likely to initiate breastfeeding than
      were multiparous controls (odds ratio [OR] = 6.4; 95% confidence interval [CI] =
      1.9-20.8). Similarly, those with uncertain prenatal breastfeeding intentions in
      the PC group were 7 times (OR = 7.4; 95% CI = 1.5-37.0) more likely to initiate
      breastfeeding than their control group counterparts. Among subjects partially
      breastfeeding on day 1 postpartum, those receiving PC were 12 times (OR = 11.9;
      95% CI = 1.2-111.1) more likely to breastfeed through 3 months postpartum than
      were controls. These findings have important implications to the Supplemental
      Food Program for Women, Infants and Children.

PMID- 15479658
TI  - Transfer of celecoxib into human milk.
AB  - The aim of this study was to investigate the transfer of celecoxib into human
      milk. In one group of 3 breastfeeding patients on celecoxib at steady state, milk
      levels were determined at set intervals over 24 hours. Plasma levels were
      determined in 2 of their infants, age 17 and 22 months. In a second group of 2
      subjects, intravenous lines were placed and a single 200-mg dose of celecoxib was
      followed by multiple paired plasma and milk samples over 8 hours. The mean milk
      to-plasma ratio for celecoxib was 0.23 (95% confidence interval [CI]: 0.15-0.31).
      The average concentration of celecoxib in milk during the 8-hour dosing interval
      was 66 microg/L (95% CI: 41-89). The absolute infant dose averaged 9.8
      microg/kg/d (95% CI: 6.2-13.4); the mean relative infant dose was 0.30%.
      Therefore, the average clinical dose transferred to the infant daily would be
      approximately 0.3% of the weight-adjusted maternal dose. The authors suggest that
      the use of celecoxib in breastfeeding mothers at these doses is very unlikely to
      cause untoward effects in breastfed infants.

PMID- 15479659
TI  - Teenage mothers and breastfeeding: does paternal age make a difference?
AB  - This descriptive investigation explores the impact of paternal age on a teenage
      mother's decision regarding infant-feeding method during the postpartum hospital
      stay. Eighty-six teenagers who delivered a live birth were asked the age of the
      fathers of their babies and what, if any, influence the fathers had on infant
      feeding. Although the fathers of the babies frequently voiced an opinion
      regarding infant feeding, teenage mothers partnered with older men were less
      likely to breastfeed during the postpartum hospital stay than were teenagers
      partnered with male peers. Implications for future research and clinical nursing
      practice are presented.

PMID- 15479660
TI  - Do tongue ties affect breastfeeding?
AB  - This study assessed indications for and safety and outcome of simple division of
      tongue tie without an anesthetic. There were 215 infants younger than 3 months
      (mean 0-19 days) who had major problems breastfeeding, despite professional
      support. Symptoms, tongue tie details, safety of division, and complications were
      recorded. Feeding was assessed by the mothers immediately, at 24 hours, and 3
      months after division. Prior to division, 88% had difficulty latching, 77% of
      mothers experienced nipple trauma, and 72% had a continuous feeding cycle. During
      division, 18% slept throughout; 60% cried more after division (mean 0-15
      seconds). There were no significant complications. Within 24 hours, 80% were
      feeding better. Overall, 64% breastfed for at least 3 months (UK national average
      is 30%). Initial assessment, diagnosis, and help, followed by division and
      subsequent support by a qualified lactation consultant, might ensure that even
      more mothers and infants benefit from breastfeeding.

PMID- 15479661
TI  - Promoting, protecting, and supporting breastfeeding in a community with a high
      rate of tobacco use.

PMID- 15479662
TI  - Insight from a breastfeeding peer support pilot program for husbands and fathers
      of Texas WIC participants.
AB  - A Father-to-Father Breastfeeding Support Pilot Program conducted by the Texas
      Department of Health provides a model of a viable way to increase breastfeeding
      rates in the Special Supplemental Nutrition Program for Women, Infants, and
      Children (WIC Program). The pilot concept was based on previous success with a
      breastfeeding peer counselor program and research documenting the father's
      attitude as an important influence on a mother's decision to breastfeed. Peer
      dads are fathers of breastfed infants participating in the WIC Program. They are
      recruited, trained, and hired to give breastfeeding and parenting information to
      other WIC fathers. WIC fathers rated the information they received as "very
      important" and indicated that counseling sessions would help them support their
      infants'mothers with breastfeeding and be better fathers. Breastfeeding
      initiation rates increased at clinics employing peer dads. Father-to-father
      breastfeeding education was successful in educating and empowering fathers,
      enabling them to support their breastfeeding family members.

PMID- 15479666
TI  - Advances in our understanding of the pathology of chronic intestinal pseudo
      obstruction.
AB  - Chronic intestinal pseudo-obstruction (CIP) represents a particularly difficult
      clinical challenge. It is a rare and highly morbid syndrome characterised by
      impaired gastrointestinal propulsion together with symptoms and signs of bowel
      obstruction in the absence of any lesions occluding the gut lumen. CIP can be
      classified as either "secondary" to a wide array of recognised pathological
      conditions or "idiopathic" (CIIP). This review will focus on CIIP, and
      specifically on the underlying pathological abnormalities. Combined clinical and
      histopathological studies are needed to highlight new perspectives in the
      understanding and management of chronic intestinal pseudo-obstruction.

PMID- 15479667
TI  - Unusual complication of tuberous sclerosis complex.

PMID- 15479668
TI  - Importance of anti- and pro-nociceptive mechanisms in human disease.

PMID- 15479669
TI  - T cell apoptosis and inflammatory bowel disease.

PMID- 15479670
TI  - NOD2 mutations and Crohn's disease: are Paneth cells and their antimicrobial
      peptides the link?

PMID- 15479671
TI  - Aerophagia, gastric, and supragastric belching: a study using intraluminal
      electrical impedance monitoring.
AB  - BACKGROUND: Patients with aerophagia are believed to have excessive belches due
      to air swallowing. Intraluminal impedance monitoring has made it possible to
      investigate the validity of this concept. METHODS: The authors measured
      oesophageal pH and electrical impedance before and after a meal in 14 patients
      with excessive belching and 14 healthy controls and identified patterns of air
      transport through the oesophagus. The size of the gastric air bubble was measured
      radiographically. In four patients prolonged oesophageal manometry was performed
      simultaneously. RESULTS: In all subjects, impedance tracings showed that a
      significant amount of air is propulsed in front of about a third of the swallow
      induced peristaltic waves. Two types of retrograde gas flow through the
      oesophagus (belch) were observed. In the first type air flowed from the stomach
      through the oesophagus in oral direction ("gastric belch"). In the second type
      air entered the oesophagus rapidly from proximal and was expulsed almost
      immediately in oral direction ("supragastric belch"). The incidence of air
      containing swallows and gastric belches was similar in patients and controls but
      supragastric belches occurred exclusively in patients. There was no evidence of
      lower oesophageal sphincter relaxation during supragastric belches. Gastric air
      bubble size was not different between the two groups. CONCLUSIONS: In patients
      with excessive belching the incidence of gaseous reflux from stomach to
      oesophagus is similar to that in healthy subjects. Their excess belching activity
      follows a distinct pattern, characterised by rapid antegrade and retrograde flow
      of air in the oesophagus that does not reach the stomach.

PMID- 15479672
TI  - Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic
      cannabis abuse.
AB  - BACKGROUND AND AIMS: To explore the association between chronic cannabis abuse
      and a cyclical vomiting illness that presented in a series of cases in South
      Australia. METHODS: Nineteen patients were identified with chronic cannabis abuse
      and a cyclical vomiting illness. For legal and ethical reasons, all patients were
      counselled to cease all cannabis abuse. Follow up was provided with serial urine
      drug screen analysis and regular clinical consultation to chart the clinical
      course. Of the 19 patients, five refused consent and were lost to follow up and
      five were excluded on the basis of confounders. The remaining nine cases are
      presented here and compared with a published case of psychogenic vomiting.
      RESULTS: In all cases, including the published case, chronic cannabis abuse
      predated the onset of the cyclical vomiting illness. Cessation of cannabis abuse
      led to cessation of the cyclical vomiting illness in seven cases. Three cases,
      including the published case, did not abstain and continued to have recurrent
      episodes of vomiting. Three cases rechallenged themselves after a period of
      abstinence and suffered a return to illness. Two of these cases abstained again,
      and became and remain well. The third case did not and remains ill. A novel
      finding was that nine of the 10 patients, including the previously published
      case, displayed an abnormal washing behaviour during episodes of active illness.
      CONCLUSIONS: We conclude that chronic cannabis abuse was the cause of the
      cyclical vomiting illness in all cases, including the previously described case
      of psychogenic vomiting.

PMID- 15479675
TI  - A phenomenal response to treatment by an advanced tumour.

PMID- 15479673
TI  - A genetic test which can be used to diagnose adult-type hypolactasia in children.
AB  - BACKGROUND/AIMS: Adult-type hypolactasia (primary lactose malabsorption) affects
      most of world's human population and limits the use of fresh milk due to lactose
      intolerance. The diagnosis of adult-type hypolactasia has been difficult to
      establish because of unsatisfactory diagnostic methods. C/T(-13910) single
      nucleotide polymorphism residing 13910 base pairs from the 5' end of the lactase
      gene has been shown to be associated with lactase persistence. The aim of the
      study was to assess the applicability of the C/T(-13910) variant as a diagnostic
      test for adult-type hypolactasia during childhood. METHODS: Intestinal biopsies
      were obtained from 329 children and adolescents of African, Finnish, and other
      White origins aged 0.1-20 years undergoing upper gastrointestinal endoscopy
      because of abdominal complaints. The biopsies were assayed for lactase, sucrase,
      and maltase activity and genotyped for the C/T(-13910) variant using polymerase
      chain reaction minisequencing. RESULTS: The frequency of the C/C(-13910) genotype
      defining lactase non-persistence was well in agreement in this study with
      published figures for the prevalences of adult-type hypolactasia in Africans and
      Whites. The C/C(-13910) genotype was associated with very low lactase activity
      (<10 U/g protein) in the majority of children tested at 8 years of age and in
      every child older than 12 years of age giving a specificity of 100% and
      sensitivity of 93% for the genetic test. The decline of lactase activity was
      somewhat earlier in African compared with Finnish children with C/C(-13910)
      genotype (p<0.03). CONCLUSIONS: Genetic test of C/T(-13910) polymorphism can be
      used as a first stage screening test for adult-type hypolactasia.

PMID- 15479674
TI  - Inhibitory actions of a high fibre diet on intestinal gas transit in healthy
      volunteers.
AB  - BACKGROUND: Fibre treatment often produces gaseous symptoms which have been
      attributed to fermentation by colonic bacteria with increased gas production.
      Effects of fibre ingestion on intestinal gas flow are unexplored. AIMS: We aimed
      to test the hypothesis that consumption of a high fibre diet retards gas transit.
      SUBJECTS: Ten healthy volunteers participated. METHODS: To investigate the
      effects of fibre on gas dynamics, physiological gas mixtures were jejunally
      perfused at 12 ml/min x 2 hours after a standard diet for seven days with and
      without psyllium 30 g/day in a crossover fashion. Gas was collected from an
      intrarectal catheter to bypass the anus and evacuation was quantified in real
      time using a barostat. RESULTS: On initiating gas perfusion under control
      conditions, an initial lag phase with no gas expulsion was observed (1129 (274)
      seconds). Thereafter, gas evacuation from the rectum proceeded with cumulative
      volumes of 1429 (108) ml by the end of the second hour. Evacuation was pulsatile
      with passage of 20.9 (2.5) boluses, with mean volumes of 68.2 (5.0) ml. Fibre
      prolonged the lag time (2265 (304) seconds; p<0.05) and reduced cumulative gas
      evacuation volumes (1022 (80) ml; p<0.05). Decreased gas evacuation resulted from
      reductions in the numbers of bolus passages (14.2 (1.1); p<0.05) but not bolus
      volumes (70.7 (3.4) ml; p = 0.66). CONCLUSIONS: Consumption of a high fibre diet
      retards intestinal gas transit by decreasing bolus propulsion to the rectum.
      Thus, in addition to increasing gas production by colonic flora, fibre ingestion
      may elicit gaseous symptoms by promoting gas retention.

PMID- 15479676
TI  - Deranged smooth muscle alpha-actin as a biomarker of intestinal pseudo
      obstruction: a controlled multinational case series.
AB  - BACKGROUND AND AIMS: Chronic idiopathic intestinal pseudo-obstruction (CIIP) is a
      severe motility disorder associated with significant morbidity. Several
      histopathological (neuropathic and myopathic) phenotypes have been described but
      only a single adult with jejunal smooth (circular) muscle alpha-actin deficiency.
      We present a prospective multinational case series investigating smooth muscle
      alpha-actin deficiency as a biomarker of this disease. METHODS: A total of 115
      fully clinically and physiologically (including prolonged (24 hour) ambulatory
      jejunal manometry) characterised CIIP patients from three European centres were
      studied. Immunohistochemical localisation of actins and other cytoskeletal
      proteins were performed on laparoscopic full thickness jejunal biopsies and
      compared with adult controls. Distribution of alpha-actin was also characterised
      in other gut regions and in the developing human alimentary tract. RESULTS:
      Twenty eight of 115 (24%) CIIP patient biopsies had absent (n = 22) or partial (n
      = 6) jejunal smooth muscle alpha-actin immunostaining in the circular muscle
      layer. In contrast, smooth muscle alpha-actin staining was preserved in the
      longitudinal muscle and in adult jejunal controls (n = 20). Comparative study of
      other adult alimentary tract regions and fetal small intestine, suggested
      significant spatial and temporal variations in smooth muscle alpha-actin
      expression. CONCLUSIONS: The ability to modulate alpha-smooth muscle actin
      expression, evident in development, is maintained in adult life and may be
      influenced by disease, rendering it a valuable biomarker even in the absence of
      other structural abnormalities.

PMID- 15479677
TI  - Bamboo trees in the stomach.

PMID- 15479678
TI  - PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional
      constipation: a double blind, randomised, controlled, multicentre trial.
AB  - BACKGROUND: Recently, polyethylene glycol (PEG 3350) has been suggested as a good
      alternative laxative to lactulose as a treatment option in paediatric
      constipation. However, no large randomised controlled trials exist evaluating the
      efficacy of either laxative. AIMS: To compare PEG 3350 (Transipeg: polyethylene
      glycol with electrolytes) with lactulose in paediatric constipation and evaluate
      clinical efficacy/side effects. PATIENTS: One hundred patients (aged 6 months-15
      years) with paediatric constipation were included in an eight week double
      blinded, randomised, controlled trial. METHODS: After faecal disimpaction,
      patients <6 years of age received PEG 3350 (2.95 g/sachet) or lactulose (6
      g/sachet) while children > or =6 years started with 2 sachets/day. Primary
      outcome measures were: defecation and encopresis frequency/week and successful
      treatment after eight weeks. Success was defined as a defecation frequency > or
      =3/week and encopresis < or =1 every two weeks. Secondary outcome measures were
      side effects after eight weeks of treatment. RESULTS: A total of 91 patients (49
      male) completed the study. A significant increase in defecation frequency (PEG
      3350: 3 pre v 7 post treatment/week; lactulose: 3 pre v 6 post/week) and a
      significant decrease in encopresis frequency (PEG 3350: 10 pre v 3 post/week;
      lactulose: 8 pre v 3 post/week) was found in both groups (NS). However, success
      was significantly higher in the PEG group (56%) compared with the lactulose group
      (29%). PEG 3350 patients reported less abdominal pain, straining, and pain at
      defecation than children using lactulose. However, bad taste was reported
      significantly more often in the PEG group. CONCLUSIONS: PEG 3350 (0.26 (0.11)
      g/kg), compared with lactulose (0.66 (0.32) g/kg), provided a higher success rate
      with fewer side effects. PEG 3350 should be the laxative of first choice in
      childhood constipation.

PMID- 15479679
TI  - Brain functional magnetic resonance imaging of rectal pain and activation of
      endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups
      and healthy controls.
AB  - BACKGROUND AND AIMS: Many patients with irritable bowel syndrome (IBS) show
      intestinal hypersensitivity to distension and sensitisation after repeated
      intestinal distensions. Abnormalities in endogenous pain inhibitory mechanisms,
      such as diffuse noxious inhibitory controls (DNIC), may be implicated and were
      investigated during brain functional magnetic resonance imaging (fMRI). PATIENTS
      AND METHODS: fMRI was performed in 10 female patients with IBS (five constipated
      (IBS-C) and five with diarrhoea (IBS-D)) and 10 female healthy controls during
      rectal balloon distension alone or during activation of DNIC by painful
      heterotopic stimulation of the foot with ice water. Rectal pain was scored with
      and without heterotopic stimulation (0 = none, 10 = maximal). RESULTS:
      Heterotopic stimulation decreased median rectal pain scores significantly in
      healthy controls (-1.5 (interquartile range -2 to -1); p = 0.001) but not in IBS
      C (-0.7 (-1 to 0.5)), IBS-D (-0.5 (-1.5 to 0.5)), or in all IBS patients (0 (-1.5
      to 1.3)). Brain activation changes during heterotopic stimulation differed highly
      significantly between IBS-C, IBS-D, and controls. The main centres affected were
      the amygdala, anterior cingulate cortex, hippocampus, insula, periaqueductal
      gray, and prefrontal cortex, which form part of the matrix controlling emotional,
      autonomic, and descending modulatory responses to pain. CONCLUSIONS: IBS-C and
      IBS-D appear to have differing abnormal endogenous pain inhibitory mechanisms,
      involving DNIC and other supraspinal modulatory pathways.

PMID- 15479680
TI  - Modulation of human dendritic cell phenotype and function by probiotic bacteria.
AB  - BACKGROUND: "Probiotic" bacteria are effective in treating some inflammatory
      bowel diseases. However which bacteria confer benefit and mechanisms of action
      remain poorly defined. Dendritic cells, which are pivotal in early bacterial
      recognition, tolerance induction, and shaping of T cell responses, may be central
      in mediating the effects of these bacteria. AIMS: To assess effects of different
      probiotic bacteria on dendritic cell function. METHODS: Human intestinal lamina
      propria mononuclear cells, whole blood, or an enriched blood dendritic cell
      population were cultured with cell wall components of the eight bacterial strains
      in the probiotic preparation VSL#3 (four lactobacilli, three bifidobacteria, and
      one streptococcal strains). Dendritic cells were identified and changes in
      dendritic cell maturation/costimulatory markers and cytokine production in
      response to probiotic bacteria were analysed by multicolour flow cytometry, in
      addition to subsequent effects on T cell polarisation. RESULTS: VSL#3 was a
      potent inducer of IL-10 by dendritic cells from blood and intestinal tissue, and
      inhibited generation of Th1 cells. Individual strains within VSL#3 displayed
      distinct immunomodulatory effects on dendritic cells; the most marked anti
      inflammatory effects were produced by bifidobacteria strains which upregulated IL
      10 production by dendritic cells, decreased expression of the costimulatory
      molecule CD80, and decreased interferon-gamma production by T cells. VSL#3
      diminished proinflammatory effects of LPS by decreasing LPS induced production of
      IL-12 while maintaining IL-10 production. CONCLUSIONS: Probiotic bacteria differ
      in their immunomodulatory activity and influence polarisation of immune responses
      at the earliest stage of antigen presentation by dendritic cells.

PMID- 15479681
TI  - Prebiotic carbohydrates modify the mucosa associated microflora of the human
      large bowel.
AB  - BACKGROUND AND AIMS: The mucosa associated flora of the large intestine is
      important in determining mucosal function although what controls its composition
      is unknown. This study has determined the effect of the prebiotic carbohydrates
      oligofructose and inulin on the mucosal flora. METHODS: An in vitro chemostat
      model of both planktonic and surface associated bacteria was used followed by an
      intervention study in 29 subjects undergoing colonoscopy. SUBJECTS: Fourteen
      subjects, recruited from colonoscopy waiting lists, supplemented their diet for
      two weeks with a mix of 7.5 g of oligofructose and 7.5 g inulin. Fifteen subjects
      were recruited at the time of colonoscopy and given no supplement. Multiple
      endoscopic biopsies were taken from the caecum, transverse and descending colon,
      and rectum. The mucosal flora was characterised by culture and to species level
      by cellular fatty acid profiles. Cell proliferation was assessed by
      immunohistochemical staining for minichromosome maintenance protein 2, Ki67, and
      proliferating cell nuclear antigen. RESULTS: In vitro prebiotics increased
      surface counts of bifidobacteria from 6.6 to 7.3 log(10) colony forming units
      (CFU) per slide (p<0.0006) with no significant changes in planktonic bacteria. In
      the feeding study, prebiotics increased mucosal bifidobacteria (log CFU/g mucosa
      (SEM)) in both the proximal (control 5.3 (0.4) v prebiotic 6.3 (0.3)) (p = 0.059)
      and distal (control 5.2 (0.3) v prebiotic 6.4 (0.3)) colon (p = 0.01).
      Lactobacilli were also increased (3.0 (0.1) v 3.7 (0.2) (p = 0.02) in the
      proximal and 3.1 (0.1) v 3.6 (0.2) (p = 0.04) in the distal colon, respectively).
      There were significantly more eubacteria in fed subjects but no changes in total
      anaerobes clostridia, bacteroides, or coliforms, nor in proliferation indices.
      CONCLUSION: Prebiotic carbohydrates can change the composition of the mucosa
      associated flora significantly.

PMID- 15479682
TI  - Maintaining remission of ulcerative colitis with the probiotic Escherichia coli
      Nissle 1917 is as effective as with standard mesalazine.
AB  - BACKGROUND AND AIMS: Evidence exists for the pathogenic role of the enteric flora
      in inflammatory bowel disease. Probiotics contain living microorganisms which
      exert health effects on the host. We compared the efficacy in maintaining
      remission of the probiotic preparation Escherichia coli Nissle 1917 and
      established therapy with mesalazine in patients with ulcerative colitis. PATIENTS
      AND METHODS: In total, 327 patients were recruited and assigned to a double
      blind, double dummy trial to receive either the probiotic drug 200 mg once daily
      (n = 162) or mesalazine 500 mg three times daily (n = 165). The study lasted for
      12 months and patients were assessed by clinical and endoscopic activity indices
      (Rachmilewitz) as well as by histology. The primary aim of the study was to
      confirm equivalent efficacy of the two drugs in the prevention of relapses.
      RESULTS: The per protocol analysis revealed relapses in 40/110 (36.4%) patients
      in the E coli Nissle 1917 group and 38/112 (33.9%) in the mesalazine group
      (significant equivalence p = 0.003). Subgroup analyses showed no differences
      between the treatment groups in terms of duration and localisation of disease or
      pretrial treatment. Safety profile and tolerability were very good for both
      groups and were not different. CONCLUSIONS: The probiotic drug E coli Nissle 1917
      shows efficacy and safety in maintaining remission equivalent to the gold
      standard mesalazine in patients with ulcerative colitis. The effectiveness of
      probiotic treatment further underlines the pathogenetic significance of the
      enteric flora.

PMID- 15479683
TI  - Divergent cell cycle kinetics underlie the distinct functional capacity of
      mucosal T cells in Crohn's disease and ulcerative colitis.
AB  - BACKGROUND: Different abnormalities of T cell effector function distinguish
      Crohn's disease (CD) from ulcerative colitis (UC). Because cell cycling
      determines effector function, pathogenic events in CD and UC may depend on cell
      cycle changes unique to each condition. METHODS: Cell cycle kinetics, cycle
      regulatory molecule expression, apoptosis, caspase and telomerase activity, and
      cellular expansion were evaluated in CD2 and CD3 activated control, CD, and UC
      lamina propria T cells. RESULTS: Compared with normal cells, CD T cells cycle
      faster, express increased phosphorylated Rb and decreased phosphorylated p53
      levels, display less caspase activity but more telomerase activity, die less, and
      undergo vigorous cellular expansion. In contrast, UC T cells cycle slower,
      express normal levels of phosphorylated Rb and p53, display more caspase activity
      but have no telomerase activity, die more, and have a limited capacity to expand.
      CONCLUSIONS: T cell cycle abnormalities in CD indicate a state of hyperreactivity
      compatible with loss of tolerance, but a hyporeactive state compatible with
      anergy in UC. Thus distinct and divergent T cell cycle characteristics underlie
      the pathogenesis of the two main forms of inflammatory bowel disease.

PMID- 15479684
TI  - Induction of T lymphocyte apoptosis by sulphasalazine in patients with Crohn's
      disease.
AB  - BACKGROUND: Lamina propria T lymphocytes (LPL) of the intestinal mucosa are
      chronically activated in Crohn's disease (CD). Defective apoptosis of activated
      LPL was proposed as a key pathogenic mechanism. In fact, increased expression of
      antiapoptotic molecules was observed in CD LPL. In the present work, we aimed to
      analyse the effects and underlying molecular mechanisms of 5-amino salicylic acid
      (5-ASA) and derivatives on apoptosis of LPL and peripheral blood lymphocytes
      (PBL) in patients with CD compared with ulcerative colitis (UC) and in non
      inflammatory controls. METHODS: PBL and LPL were isolated by Ficoll-Hypopaque
      gradient centrifugation and the EGTA-collagenase method, respectively. PBL/LPL
      were stimulated with FasL, 5-ASA, sulphapyridine, and sulphasalazine for 24/48
      hours and apoptosis was quantified by flow cytometry (annexin V- propidium iodide
      method) and immunofluorescence. The molecular mechanisms of drug induced
      apoptosis were analysed in wild-type and FADD-/- Jurkat T cells using western
      blots and caspase assays. RESULTS: While PBL displayed a normal apoptosis pattern
      after Fas stimulation in patients with active CD, LPL from inflammatory areas
      were highly resistant. Comparable resistance to apoptosis was observed in LPL of
      UC patients. In contrast with 5-ASA, which did not induce apoptosis in
      lymphocytes, sulphasalazine proved to be a potent proapoptotic agent.
      Sulphasalazine induced T lymphocyte apoptosis was independent of the Fas pathway
      but associated with marked downregulation of antiapoptotic bcl-xl and bcl2,
      activation of the mitochondrial apoptosis signalling pathway, and subsequent
      activation of caspase-9 and caspase-3. CONCLUSION: The beneficial effect of
      sulphasalazine in treating inflammatory bowel disease is at least in part
      attributable to its proapoptotic effects on LPL which allows potent
      downregulation of lymphocyte activation.

PMID- 15479685
TI  - A randomised controlled trial to assess the effectiveness and cost of a patient
      orientated self management approach to chronic inflammatory bowel disease.
AB  - OBJECTIVES: We developed a patient centred approach to chronic disease self
      management by providing information designed to promote patient choice. We then
      conducted a randomised controlled trial of the approach in inflammatory bowel
      disease (IBD) to assess whether it could alter clinical outcome and affect health
      service use. DESIGN: A multicentre cluster randomised controlled trial. SETTING:
      The trial was conducted in the outpatient departments of 19 hospitals with
      randomisation by treatment centre, 10 control sites, and nine intervention sites.
      For patients at intervention sites, an individual self management plan was
      negotiated and written information provided. PARTICIPANTS: A total of 700
      patients with established inflammatory bowel disease were recruited. MAIN OUTCOME
      MEASURES: Main outcome measures recorded at one year were: quality of life,
      health service resource use, and patient satisfaction. Secondary outcomes
      included measures of enablement-confidence to cope with the condition. RESULTS:
      One year following the intervention, self managing patients had made fewer
      hospital visits (difference -1.04 (95% confidence interval (CI) -1.43 to -0.65);
      p<0.001) without increase in the number of primary care visits, and quality of
      life was maintained without evidence of anxiety about the programme. The two
      groups were similar with respect to satisfaction with consultations. Immediately
      after the initial consultation, those who had undergone self management training
      reported greater confidence in being able to cope with their condition
      (difference 0.90 (95% CI 0.12-1.68); p<0.03). CONCLUSIONS: Adoption of this
      approach for the management of chronic disease such as IBD in the NHS and other
      managed health care organisations would considerably reduce health provision
      costs and benefit disease control.

PMID- 15479686
TI  - A randomised, controlled, double blind, escalating dose study of alicaforsen
      enema in active ulcerative colitis.
AB  - OBJECTIVE: To evaluate the safety and efficacy of an enema formulation of
      alicaforsen, an antisense inhibitor of intercellular adhesion molecule, after 1,
      3, and 6 months. METHODS: This was a randomised, placebo controlled, double
      blind, escalating dose multicentre study in 40 patients with mild to moderately
      active distal ulcerative colitis (disease activity index (DAI) 4-10). Patients
      were assigned to four dosing cohorts of 10 patients each (eight active, two
      placebo). Each patient received 60 ml of alicaforsen enema (0.1, 0.5, 2, or 4
      mg/ml or placebo) once daily for 28 consecutive days. Safety and efficacy (DAI
      and clinical activity index) scores were evaluated up to six months after
      initiation of dosing. RESULTS: At day 29, alicaforsen enema resulted in dose
      dependent improvement in DAI (overall p = 0.003). Alicaforsen 4 mg/ml improved
      DAI by 70% compared with the placebo response of 28% (p = 0.004). Alicaforsen 2
      and 4 mg/ml improved DAI status by 72% and 68% compared with a placebo response
      of 11.5% at month 3 (p = 0.016 and 0.021, respectively). Specifically, DAI
      improved from 5.6 to 1.6 and from 6.3 to 2.5 in the 2 and 4 mg/ml groups compared
      with placebo (7.5 to 6.1). None of the patients in the 4 mg/ml group compared
      with 4/8 placebo patients required additional medical or surgical intervention
      over baseline during the six month period after starting the enema treatment. The
      safety profile was favourable. CONCLUSIONS: Alicaforsen enema showed promising
      acute and long term benefit in patients with mild to moderate descending
      ulcerative colitis. Alicaforsen enemas had a favourable safety profile. These
      findings require verification in larger randomised controlled clinical trials.

PMID- 15479687
TI  - An important pitfall in diagnosing gall bladder cancer.

PMID- 15479688
TI  - Oral contrast enhanced bowel ultrasonography in the assessment of small intestine
      Crohn's disease. A prospective comparison with conventional ultrasound, x ray
      studies, and ileocolonoscopy.
AB  - BACKGROUND/ AIM: Although ultrasound (US) has proved to be useful in intestinal
      diseases, barium enteroclysis (BE) remains the gold standard technique for
      assessing patients with small bowel Crohn's disease (CD). The ingestion of
      anechoic non-absorbable solutions has been recently proposed in order to distend
      intestinal loops and improve small bowel visualisation. The authors' aim was to
      evaluate the accuracy of oral contrast US in finding CD lesions, assessing their
      extent within the bowel, and detecting luminal complications, compared with BE
      and ileocolonoscopy. METHODS: 102 consecutive patients with proven CD, having
      undergone complete x ray and endoscopic evaluation, were enrolled in the study.
      Each US examination, before and after the ingestion of a polyethylene glycol
      (PEG) solution (500-800 ml), was performed independently by two sonographers
      unaware of the results of other diagnostic procedures. The accuracy of
      conventional and contrast enhanced US in detecting CD lesions and luminal
      complications, as well as the extent of bowel involvement, were determined.
      Interobserver agreement between sonographers with both US techniques was also
      estimated. RESULTS: After oral contrast, satisfactory distension of the
      intestinal lumen was obtained in all patients, with a mean time to reach the
      terminal ileum of 31.4 (SD 10.9) minutes. Overall sensitivity of conventional and
      oral contrast US in detecting CD lesions were 91.4% and 96.1%, respectively. The
      correlation coefficient between US and x ray extent of ileal disease was r1 =
      0.83 (p<0.001) before and r2 = 0.94 (p<0.001) after PEG ingestion; r1 versus r2
      p<0.01. Sensitivity in detecting strictures was 74% for conventional US and 89%
      for contrast US. Overall interobserver agreement for bowel wall thickness and
      disease location within the small bowel was already good before but significantly
      improved after PEG ingestion. CONCLUSIONS: Oral contrast bowel US is comparable
      with BE in defining anatomic location and extension of CD and superior to
      conventional US in detecting luminal complications, as well as reducing
      interobserver variability between sonographers. It may be therefore regarded as
      the first imaging procedure in the diagnostic work up and follow up of small
      intestine CD.

PMID- 15479689
TI  - NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal
      alpha-defensin expression.
AB  - BACKGROUND: Mutations in NOD2, a putative intracellular receptor for bacterial
      peptidoglycans, are associated with a subset of Crohn's disease but the molecular
      mechanism linking this protein with the disease pathogenesis remains unclear.
      Human alpha defensins (HD-5 and HD-6) are antibiotic effector molecules
      predominantly expressed in Paneth cells of the ileum. Paneth cells also express
      NOD2. To address the hypothesis that the function of NOD2 may affect expression
      of Paneth cell defensins, we compared their expression levels with respect to
      NOD2 mutations in Crohn's disease. METHODS: Forty five Crohn's disease patients
      (24 with NOD2 mutations, 21 with wild-type NOD2) and 12 controls were studied.
      Real time reverse transcription-polymerase chain reaction was performed with
      mucosal mRNA for HD-5, HD-6, lysozyme, secretory phospholipase A2 (sPLA2), tumour
      necrosis factor alpha, interleukin 8, and human hypoxanthine
      phosphoribosyltransferase (housekeeping gene). Immunohistochemistry with anti-HD
      5 and histological Paneth cell staining were performed in 10 patients with NOD2
      mutations or wild-type genotypes. RESULTS: Ileal expression of HD-5 and HD-6, but
      not sPLA2 or lysozyme, were diminished in affected ileum, and the decrease was
      significantly more pronounced in patients with NOD2 mutations. In the colon, HD
      5, HD-6, and sPLA2 were increased during inflammation in wild-type but not in
      NOD2 mutated patients. In both the colon and ileum, proinflammatory cytokines and
      lysozyme were unaffected by NOD2 status. Immunohistochemistry identified Paneth
      cells as the sole source of HD-5. CONCLUSION: As alpha defensins are important in
      the mucosal antibacterial barrier, their diminished expression may explain, in
      part, the bacterial induced mucosal inflammation and ileal involvement of Crohn's
      disease, especially in the case of NOD2 mutations.

PMID- 15479690
TI  - Increased intrahepatic cyclooxygenase 2, matrix metalloproteinase 2, and matrix
      metalloproteinase 9 expression is associated with progressive liver disease in
      chronic hepatitis C virus infection: role of viral core and NS5A proteins.
AB  - BACKGROUND: Cyclooxygenase 2 (COX-2) and matrix metalloproteinases (MMPs) have
      been implicated in tissue injury and fibrogenesis in animal models but little is
      known regarding their role in hepatitis C virus (HCV) related liver disease in
      humans. AIMS: To characterise the intrahepatic expression pattern of COX-2 and
      MMPs in chronic HCV infection and determine whether HCV core and NS5A proteins
      could promote their expression in cultured hepatocyte derived cell lines.
      PATIENTS: Thirty two anti-HCV+ and 10 anti-HCV- patients were studied. METHODS:
      Western blot, reverse transcription-polymerase chain reaction (RT-PCR), enzyme
      immunoassay, and immunohistochemistry were used to assess the expression pattern
      of COX-2 and MMPs in liver biopsy samples from all patients. COX-2 gene
      expression and MMP-9 protein levels were also determined by immunoblot, RT-PCR,
      and luciferase assays in core and NS5A transfected hepatocyte derived cells.
      RESULTS: The intrahepatic expression level of COX-2, MMP-2, and MMP-9 was
      significantly higher in HCV+ than in HCV- patients, increasing with the fibrotic
      stage of liver disease. We further demonstrated that COX-2 mRNA, protein, and
      activity were induced in resting and activated core and NS5A transfectants. Both
      viral proteins induced transcriptional activity of the COX-2 gene promoter
      whereas core, but not NS5A, exerted an inducer effect on MMP-9 protein levels in
      cultured hepatocyte derived cells. CONCLUSIONS: Intrahepatic COX-2, MMP-2, and
      MMP-9 overexpression is associated with progressive hepatic fibrosis in chronic
      HCV infection, suggesting their pathogenic role in fibrogenesis. HCV core and
      NS5A proteins were able to upregulate COX-2 and MMP-9 gene expression in
      hepatocyte derived cells, providing a potential mechanism for hepatic fibrosis
      during chronic HCV infection.

PMID- 15479691
TI  - Multispecific T cell response and negative HCV RNA tests during acute HCV
      infection are early prognostic factors of spontaneous clearance.
AB  - BACKGROUND/AIMS: Hepatitis C virus (HCV) infection results in a high frequency of
      chronic disease. The aim of this study was to identify early prognostic markers
      of disease resolution by performing a comprehensive analysis of viral and host
      factors during the natural course of acute HCV infection. METHODS: The clinical
      course of acute hepatitis C was determined in 34 consecutive patients.
      Epidemiological and virological parameters, as well as cell mediated immunity
      (CMI) and distribution of human leukocyte antigens (HLA) alleles were analysed.
      RESULTS: Ten out of 34 patients experienced self-limiting infection, with most
      resolving patients showing fast kinetics of viral clearance: at least one
      negative HCV RNA test during this phase predicted a favourable outcome. Among
      other clinical epidemiological parameters measured, the self-limiting course was
      significantly associated with higher median peak bilirubin levels at the onset of
      disease, and with the female sex, but only the latter parameter was independently
      associated after multivariate analysis. No significant differences between self
      limiting or chronic course were observed for the distribution of DRB1 and DQB1
      alleles. HCV specific T cell response was more frequently detected during acute
      HCV infection, than in patients with chronic HCV disease. A significantly broader
      T cell response was found in patients with self-limiting infection than in those
      with chronic evolving acute hepatitis C. CONCLUSION: The results suggest that
      host related factors, in particular sex and CMI, play a crucial role in the
      spontaneous clearance of this virus. Most importantly, a negative HCV RNA test
      and broad CMI within the first month after onset of the symptoms represent very
      efficacious predictors of viral clearance and could thus be used as criteria in
      selecting candidates for early antiviral treatment.

PMID- 15479692
TI  - A role for thrombin in liver fibrosis.
AB  - BACKGROUND/AIM: Several lines of evidence incriminate the serine proteinase
      thrombin in liver fibrogenesis either through its procoagulant function or its
      signaling via cell-surface receptors. The aim of this study was therefore to
      evaluate the effect of thrombin inhibition on experimental liver fibrosis.
      METHODS: Fibrosis was induced in rats by administration of CCl4 for either three
      or seven weeks. Oral administration of the thrombin antagonist SSR182289 started
      one week after the start of CCl4 intoxication. Fibrosis and the area occupied by
      alpha smooth muscle actin (ASMA) positive cells were quantified with
      histomorphometry. Expression of fibrosis related genes was measured by real time
      RT-PCR. RESULTS: After three weeks of CCl4, treatment with SSR182289 did not
      significantly decrease the area of fibrosis but significantly decreased the area
      of ASMA positive cells by 22% (p = 0.03) and the expression of TIMP-1 mRNA by 52%
      (p = 0.02). There was no effect on gene expression of collagen I, MMP-2, or TIMP
      2. After seven weeks of CCl4, treatment with SSR182289 resulted in a significant
      decrease in fibrosis (-30%, p = 0.04) and ASMA positive areas (-35%, p = 0.05).
      SSR182289 alone had no effect on the measured parameters. Additionally, it did
      not alleviate the acute toxicity of CCl4 as shown by measuring levels of serum
      aminotransferases and the area of necrosis. CONCLUSIONS: These data provide
      evidence that thrombin antagonism can reduce liver fibrogenesis. The early effect
      of SSR182289 on ASMA and TIMP-1 expression suggests that it is beneficial in
      reducing fibrogenic cell activation.

PMID- 15479693
TI  - Antidiabetic thiazolidinediones inhibit invasiveness of pancreatic cancer cells
      via PPARgamma independent mechanisms.
AB  - BACKGROUND/AIMS: Thiazolidinediones (TZD) are a new class of oral antidiabetic
      drugs that have been shown to inhibit growth of some epithelial cancer cells.
      Although TZD were found to be ligands for peroxisome proliferators activated
      receptor gamma (PPARgamma) the mechanism by which TZD exert their anticancer
      effect is currently unclear. Furthermore, the effect of TZD on local motility and
      metastatic potential of cancer cells is unknown. The authors analysed the effects
      of two TZD, rosiglitazone and pioglitazone, on invasiveness of human pancreatic
      carcinoma cell lines in order to evaluate the potential therapeutic use of these
      drugs in pancreatic adenocarcinoma. METHODS: Expression of PPARgamma in human
      pancreatic adenocarcinomas and pancreatic carcinoma cell lines was measured by
      reverse transcription polymerase chain reaction and confirmed by western blot
      analysis. PPARgamma activity was evaluated by transient reporter gene assay.
      Invasion assay was performed in modified Boyden chambers. Gelatinolytic and
      fibrinolytic activity were evaluated by gel zymography. RESULTS: TZD inhibited
      pancreatic cancer cells' invasiveness, affecting gelatinolytic and fibrinolytic
      activity with a mechanism independent of PPARgamma activation and involving MMP-2
      and PAI-1 expression. CONCLUSION: TZD treatment in pancreatic cancer cells has
      potent inhibitory effects on growth and invasiveness suggesting that these drugs
      may have application for prevention and treatment of pancreatic cancer in humans.

PMID- 15479694
TI  - Regression of idiopathic thrombocytopenic purpura after endoscopic mucosal
      resection of gastric mucosa associated lymphoid tissue lymphoma.
AB  - Recent reports have suggested an association between Helicobacter pylori
      infection and both gastric mucosa associated lymphoid tissue (MALT) lymphoma and
      thrombocytopenic purpura. Although treatments eradicating H pylori lead to
      regression of these diseases in some cases, the exact mechanisms are still
      controversial. This case report describes a patient with thrombocytopenic purpura
      accompanied by an early stage gastric MALT lymphoma. Endoscopic mucosal resection
      of the lesion in this patient led to dramatic regression of thrombocytopenic
      purpura, and t(11;18)(q21;q21), which means resistance more likely to H pylori
      eradication therapy, was confirmed by fluorescence in situ hybridisation. There
      is no evidence of recurrence and his platelet count is within normal limits after
      24 months of follow up. This is the first case report describing regression of
      thrombocytopenic purpura after mucosal resection of a gastric MALT lymphoma. We
      suggest that while some cases of thrombocytopenic purpura may be induced by H
      pylori, others may be due to an autoreactive antibody produced by MALT lymphoma B
      cells.

PMID- 15479695
TI  - Apoptosis and colorectal cancer.

PMID- 15479696
TI  - Value of genetic testing in the management of pancreatitis.

PMID- 15479697
TI  - The role of age in the protection of appendicectomy against ulcerative colitis.

PMID- 15479698
TI  - Short segment reflux: acid but no pocket?

PMID- 15479699
TI  - Influence of antisecretory drugs on Helicobacter pylori eradication rates.

PMID- 15479700
TI  - Sporadic fundic gland polyps: what happened before?

PMID- 15479701
TI  - Infallibility of a normal platelet count/spleen diameter ratio in ruling out
      oesophageal varices?

PMID- 15479702
TI  - Cytokines in portopulmonary hypertension.

PMID- 15479703
TI  - To dye or not to dye? That is beyond question! Optimising surveillance
      colonoscopy is indispensable for detecting dysplasia in ulcerative colitis.

PMID- 15479704
TI  - A big first step.
AB  - The singleton, term gestation, live birth rate per cycle initiated (BESST)
      endpoint proposed at the beginning of 2004 is a first big step which should be
      added to by the consideration of multiple pregnancy rates in relation to
      singleton rates, by recording of fetal reductions and of pregnancies resulting
      from cryopreserved material. After three or more steps we may have an accurate
      reporting system which helps patients to distinguish the pros and cons for
      singleton term delivery.

PMID- 15479705
TI  - The positive effect on determinants of physical activity of a tailored, general
      practice-based physical activity intervention.
AB  - PACE (Physician-based Assessment and Counseling for Exercise) is an
      individualized theory-based minimal intervention strategy aimed at the
      enhancement of regular physical activity. The aim of this study was to evaluate
      the effectiveness of a PACE intervention applied by general practitioners (GPs)
      on potential determinants of physical activity. A randomized controlled trial was
      conducted in 29 general practices with the following inclusion criteria for
      patients: aged between 18 and 70 years, diagnosed with hypertension,
      hypercholesterolemia and/or non-insulin-dependent diabetes mellitus, and not in
      maintenance stage for regular physical activity. The intervention consisted of
      two visits with the GP and two telephone booster calls by a physical activity
      counselor. Determinants of physical activity were assessed with questionnaires at
      baseline, and at 8-week (short), 6-month (medium) and 1-year (long) follow-up. A
      significant positive effect was observed on self-efficacy, and on the use of
      cognitive and behavioral processes of change, at both short- and medium-term
      follow-up. The intervention respondents also perceived fewer barriers for regular
      physical activity at short-term and used behavioral processes of change more at
      long-term follow-up. No intervention effect was observed for perceived benefits
      of physical activity. In conclusion, this GP-based PACE intervention resulted in
      positive changes in potential determinants of physical activity.

PMID- 15479706
TI  - Making sense of the challenge of smoking cessation during pregnancy: a
      phenomenographic approach.
AB  - In general, most women are familiar with the need to stop smoking when they are
      pregnant. In spite of this, many women find it difficult to stop. Using a
      phenomenographic approach, this study explored Swedish pregnant and post-pregnant
      women's ways of making sense of smoking during pregnancy. A total of 17 women who
      either smoked throughout pregnancy or stopped smoking during pregnancy were
      interviewed. Five different story types of how they are making sense of smoking
      during pregnancy were identified: smoking can be justified; will stop later; my
      smoking might hurt the baby; smoking is just given up; smoking must be taken
      charge of. Based on the study it is argued that the approach used in health
      education in relation to smoking cessation in antenatal care needs to move from
      information transfer and advice-giving to the creation of a dialogue. The
      starting point should be the woman's knowledge, concerns, rationalizations and
      prejudices. A model is suggested in which a woman may move in a space on three
      axes depending on life encounters, dialogue and reflections on meaning. The goal
      in health education would be to encourage movement along three axes: 'increase of
      self-efficacy towards control', 'increase awareness by reflection on meaning of
      the smoking issue' and 'avoidance of defense of the smoking behavior'.

PMID- 15479707
TI  - Researching practice: the methodological case for narrative inquiry.
AB  - Research interest in the analysis of stories has increased as researchers in many
      disciplines endeavor to see the world through the eyes of others. We make the
      methodological case for narrative inquiry as a unique means to get inside the
      world of health promotion practice. We demonstrate how this form of inquiry may
      reveal what practitioners value most in and through their practice, and the
      indigenous theory or the cause-and-consequence thinking that governs their
      actions. Our examples draw on a unique data set, i.e. 2 two years' of diaries
      being kept by community development officers in eight communities engaged in a
      primary care and community development intervention to reduce postnatal
      depression and promote the physical health of recent mothers. Narrative inquiry
      examines the way a story is told by considering the positioning of the
      actor/storyteller, the endpoints, the supporting cast, the sequencing and the
      tension created by the revelation of some events, in preference to others.
      Narrative methods may provide special insights into the complexity of community
      intervention implementation over and above more familiar research methods.

PMID- 15479708
TI  - An empirical Bayes approach to inferring large-scale gene association networks.
AB  - MOTIVATION: Genetic networks are often described statistically using graphical
      models (e.g. Bayesian networks). However, inferring the network structure offers
      a serious challenge in microarray analysis where the sample size is small
      compared to the number of considered genes. This renders many standard algorithms
      for graphical models inapplicable, and inferring genetic networks an 'ill-posed'
      inverse problem. METHODS: We introduce a novel framework for small-sample
      inference of graphical models from gene expression data. Specifically, we focus
      on the so-called graphical Gaussian models (GGMs) that are now frequently used to
      describe gene association networks and to detect conditionally dependent genes.
      Our new approach is based on (1) improved (regularized) small-sample point
      estimates of partial correlation, (2) an exact test of edge inclusion with
      adaptive estimation of the degree of freedom and (3) a heuristic network search
      based on false discovery rate multiple testing. Steps (2) and (3) correspond to
      an empirical Bayes estimate of the network topology. RESULTS: Using computer
      simulations, we investigate the sensitivity (power) and specificity (true
      negative rate) of the proposed framework to estimate GGMs from microarray data.
      This shows that it is possible to recover the true network topology with high
      accuracy even for small-sample datasets. Subsequently, we analyze gene expression
      data from a breast cancer tumor study and illustrate our approach by inferring a
      corresponding large-scale gene association network for 3883 genes.

PMID- 15479709
TI  - ParIS Genome Rearrangement server.
AB  - SUMMARY: ParIS Genome Rearrangement is a web server for a Bayesian analysis of
      unichromosomal genome pairs. The underlying model allows inversions,
      transpositions and inverted transpositions. The server generates a Markov chain
      using a Partial Importance Sampler technique, and samples trajectories of
      mutations from this chain. The user can specify several marginalizations to the
      posterior: the posterior distribution of number of mutations needed to transform
      one genome into another, length distribution of mutations, number of mutations
      that have occurred at a given site. Both text and graphical outputs are
      available. We provide a limited server, a downloadable unlimited server that can
      be installed locally on any linux/Unix operating system, and a database of
      mitochondrial gene orders.

PMID- 15479710
TI  - A simple procedure for estimating the false discovery rate.
AB  - MOTIVATION: The most used criterion in microarray data analysis is nowadays the
      false discovery rate (FDR). In the framework of estimating procedures based on
      the marginal distribution of the P-values without any assumption on gene
      expression changes, estimators of the FDR are necessarily conservatively biased.
      Indeed, only an upper bound estimate can be obtained for the key quantity pi0,
      which is the probability for a gene to be unmodified. In this paper, we propose a
      novel family of estimators for pi0 that allows the calculation of FDR. RESULTS:
      The very simple method for estimating pi0 called LBE (Location Based Estimator)
      is presented together with results on its variability. Simulation results
      indicate that the proposed estimator performs well in finite sample and has the
      best mean square error in most of the cases as compared with the procedures
      QVALUE, BUM and SPLOSH. The different procedures are then applied to real
      datasets. AVAILABILITY: The R function LBE is available at
      http://ifr69.vjf.inserm.fr/lbe CONTACT: broet@vjf.inserm.fr.

PMID- 15479711
TI  - Database driven test case generation for protein-protein docking.
AB  - We present a method for automatic test case generation for protein-protein
      docking. A consensus-type approach is proposed processing the whole PDB and
      classifying protein structures into complexes and unbound proteins by combining
      information from three different approaches (current PDB-at-a-glance
      classification, search of complexes by sequence identical unbound structures and
      chain naming). Out of this classification test cases are generated automatically.
      All calculations were run on the database. The information stored is available
      via a web interface. The user can choose several criteria for generating his own
      subset out of our test cases, e.g. for testing docking algorithms. AVAILABILITY:
      http://bibiserv.techfak.uni-bielefeld.de/agt-sdp/ CONTACT: fzoellne@techfak.uni
      bielefeld.de.

PMID- 15479712
TI  - TRbase: a database relating tandem repeats to disease genes for the human genome.
AB  - MOTIVATION: Tandem repeats are associated with disease genes, play an important
      role in evolution and are important in genomic organization and function.
      Although much research has been done on short perfect patterns of repeats, there
      has been less focus on imperfect repeats. Thus, there is an acute need for a
      tandem repeats database that provides reliable and up to date information on both
      perfect and imperfect tandem repeats in the human genome and relates these to
      disease genes. RESULTS: This paper presents a web-accessible relational tandem
      repeats database that relates tandem repeats to gene locations and disease genes
      of the human genome. In contrast to other available databases, this database
      identifies both perfect and imperfect repeats of 1-2000 bp unit lengths. The
      utility of this database has been illustrated by analysing these repeats for
      their distribution and frequencies across chromosomes and genomic locations and
      between protein-coding and non-coding regions. The applicability of this database
      to identify diseases associated with previously uncharacterized tandem repeats is
      demonstrated.

PMID- 15479713
TI  - Understanding protein dispensability through machine-learning analysis of high
      throughput data.
AB  - MOTIVATION: Protein dispensability is fundamental to the understanding of gene
      function and evolution. Recent advances in generating high-throughput data such
      as genomic sequence data, protein-protein interaction data, gene-expression data
      and growth-rate data of mutants allow us to investigate protein dispensability
      systematically at the genome scale. RESULTS: In our studies, protein
      dispensability is represented as a fitness score that is measured by the growth
      rate of gene-deletion mutants. By the analyses of high-throughput data in yeast
      Saccharomyces cerevisiae, we found that a protein's dispensability had
      significant correlations with its evolutionary rate and duplication rate, as well
      as its connectivity in protein-protein interaction network and gene-expression
      correlation network. Neural network and support vector machine were applied to
      predict protein dispensability through high-throughput data. Our studies shed
      some lights on global characteristics of protein dispensability and evolution.
      AVAILABILITY: The original datasets for protein dispensability analysis and
      prediction, together with related scripts, are available at
      http://digbio.missouri.edu/~ychen/ProDispen/ CONTACT: xudong@missouri.edu.

PMID- 15479714
TI  - Bayesian analysis of signaling networks governing embryonic stem cell fate
      decisions.
AB  - MOTIVATION: Signaling events that direct mouse embryonic stem (ES) cell self
      renewal and differentiation are complex and accordingly difficult to understand
      in an integrated manner. We address this problem by adapting a Bayesian network
      learning algorithm to model proteomic signaling data for ES cell fate responses
      to external cues. Using this model we were able to characterize the signaling
      pathway influences as quantitative, logic-circuit type interactions. Our
      experimental dataset includes measurements for 28 signaling protein
      phosphorylation states across 16 different factorial combinations of cytokine and
      matrix stimuli as reported previously. RESULTS: The Bayesian network modeling
      approach allows us to uncover previously reported signaling activities related to
      mouse ES cell self-renewal, such as the roles of LIF and STAT3 in maintaining
      undifferentiated ES cell populations. Furthermore, the network predicts novel
      influences such as between ERK phosphorylation and differentiation, or RAF
      phosphorylation and differentiated cell proliferation. Visualization of the
      influences detected by the Bayesian network provides intuition about the
      underlying physiology of the signaling pathways. We demonstrate that the Bayesian
      networks can capture the linear, nonlinear and multistate logic interactions that
      connect extracellular cues, intracellular signals and consequent cell functional
      responses.

PMID- 15479715
TI  - Improving conformational searches by geometric screening.
AB  - MOTIVATION: Conformational searches in molecular docking are a time-consuming
      process with wide range of applications. Favorable conformations of the ligands
      that successfully bind with receptors are sought to form stable ligand-receptor
      complexes. Usually a large number of conformations are generated and their
      binding energies are examined. We propose adding a geometric screening phase
      before an energy minimization procedure so that only conformations that
      geometrically fit in the binding site will be prompted for energy calculation.
      RESULTS: Geometric screening can drastically reduce the number of conformations
      to be examined from millions (or higher) to thousands (or lower). The method can
      also handle cases when there are more variables than geometric constraints. An
      early-stage implementation is able to finish the geometric filtering of
      conformations for molecules with up to nine variables in 1 min. To the best of
      our knowledge, this is the first time such results are reported
      deterministically. CONTACT: mzhang@mdanderson.org.

PMID- 15479716
TI  - Circular genome visualization and exploration using CGView.
AB  - CGView (Circular Genome Viewer) is a Java application and library for generating
      high-quality, zoomable maps of circular genomes. It converts XML or tab-delimited
      input into a graphical map (PNG, JPG or Scalable Vector Graphics format),
      complete with sequence features, labels, legends and footnotes. In addition to
      the default full view map, the program can generate a series of hyperlinked maps
      showing expanded views. The linked maps can be explored using any Web browser,
      allowing rapid genome browsing and facilitating data sharing. AVAILABILITY:
      CGView (the standalone application, library or applet), sample input, sample maps
      and documentation can be obtained from http://wishart.biology.ualberta.ca/cgview/
      CONTACT: david.wishart@ualberta.ca.

PMID- 15479717
TI  - Suppression of Nek2A in mouse early embryos confirms its requirement for
      chromosome segregation.
AB  - Nek2, a mammalian structural homologue of Aspergillus protein kinase NIMA, is
      predominantly known as a centrosomal kinase that controls centriole-centriole
      linkage during the cell cycle. However, its dynamic subcellular localization
      during mitosis suggested that Nek2 might be involved in diverse cell cycle events
      in addition to the centrosomal cycle. In order to determine the importance of
      Nek2 during mammalian development, we investigated the expression and function of
      Nek2 in mouse early embryos. Our results show that both Nek2A and Nek2B were
      expressed throughout early embryogenesis. Unlike cultured human cells, however,
      embryonic Nek2A appeared not to be destroyed upon entry into mitosis, suggesting
      that the Nek2A protein level is controlled in a unique manner during mouse early
      embryogenesis. Suppression of Nek2 expression by RNAi resulted in developmental
      defects at the second mitosis. Many of the blastomeres in Nek2-suppressed embryos
      showed abnormality in nuclear morphology, including dumbbell-like nuclei, nuclear
      bridges and micronuclei. These results indicate the importance of Nek2 for proper
      chromosome segregation in embryonic mitoses.

PMID- 15479718
TI  - Spatial mapping of integrin interactions and dynamics during cell migration by
      image correlation microscopy.
AB  - Image correlation microscopy methodology was extended and used to determine
      retrospectively the density, dynamics and interactions of alpha5-integrin in
      migrating cells. Alpha5-integrin is present in submicroscopic clusters containing
      3-4 integrins before it is discernibly organized. The integrin in nascent
      adhesions, as identified by the presence of paxillin, is approximately 1.4 times
      more concentrated, approximately 4.5 times more clustered and much less mobile
      than in surrounding regions. Thus, while integrins are clustered throughout the
      cell, they differ in nascent adhesions and appear to initiate adhesion formation,
      despite their lack of visible organization. In more mature adhesions where the
      integrin is visibly organized there are approximately 900 integrins microm(-2)
      (about fivefold higher than surrounding regions). Interestingly, alpha5-integrin
      and alpha-actinin, but not paxillin, reside in a complex throughout the cell,
      where they diffuse and flow together, even in regions where they are not
      organized. During adhesion disassembly some integrins diffuse away slowly, alpha
      actinin undergoes a directed movement at speeds similar to actin retrograde flow
      (0.29 microm min(-1)), while all of the paxillin diffuses away rapidly.

PMID- 15479719
TI  - Elongation of centriolar microtubule triplets contributes to the formation of the
      mitotic spindle in gamma-tubulin-depleted cells.
AB  - The assembly of the mitotic spindle after depletion of the major gamma-tubulin
      isotype by RNA-mediated interference was assessed in the Drosophila S2 cell line.
      Depletion of gamma-tubulin had no significant effect on the cytoskeletal
      microtubules during interphase. However, it promoted an increase in the mitotic
      index, resulting mainly in monopolar and, to a lesser extent, asymmetrical
      bipolar prometaphases lacking astral microtubules. This mitotic accumulation
      coincided with the activation of the mitotic checkpoint. Immunostaining with an
      anti-Asp antibody revealed that the spindle poles, which were always devoid of
      gamma-tubulin, were unfocused and organized into sub-spindles. Despite the marked
      depletion of gamma-tubulin, the pericentriolar proteins CP190 and centrosomin
      were recruited to the spindle pole(s), where they formed three or four dots,
      suggesting the presence of several centrioles. Electron microscopic
      reconstructions demonstrated that most of the monopolar spindles exhibited three
      or four centrioles, indicating centriole duplication with a failure in the
      separation process. Most of the centrioles were shortened, suggesting a role for
      gamma-tubulin in centriole morphogenesis. Moreover, in contrast to metaphases
      observed in control cells, in which the spindle microtubules radiated from the
      pericentriolar material, in gamma-tubulin-depleted cells, microtubule assembly
      still occurred at the poles but involved the elongation of centriolar microtubule
      triplets. Our results demonstrate that, after depletion of gamma-tubulin, the
      pericentriolar material is unable to promote efficient microtubule nucleation.
      They point to an alternative mechanism of centrosomal microtubule assembly that
      contributes to the formation of abnormal, albeit partially functional, mitotic
      spindles.

PMID- 15479720
TI  - The C-terminal domain LLKIL motif of CXCR2 is required for ligand-mediated
      polarization of early signals during chemotaxis.
AB  - HEK293 cells expressing wild-type CXCR2 recruit PH-Akt-GFP to the leading edge of
      the cell in response to chemokine. However, in cells expressing mutant CXCR2
      defective in AP-2 and HIP binding, i.e. with a mutation in the LLKIL motif, PH
      Akt-GFP does not localize to the leading edge in response to ligand. Inhibition
      of Akt/PKB by transfection of HEK 293 cells with a dominant negative (kinase
      defective) Akt/PKB inhibits CXCR2 mediated chemotaxis. FRET analysis reveals that
      membrane-bound activated Cdc42 and Rac1 localize to the leading edge of cells
      expressing wild-type CXCR2 receptor, but not in cells expressing mutant CXCR2. By
      contrast, when the activation of Cdc42 and Rac1 are monitored by affinity
      precipitation assay, cells expressing either wild-type or LLKIL mutant receptors
      show equivalent ligand induction. Altogether, these data suggest that restricted
      localized activation of Akt/PKB, Rac1 and Cdc42 is crucial for chemotactic
      responses and that events mediated by the LLKIL motif are crucial for chemotaxis.

PMID- 15479721
TI  - Hepcidin excess induces the sequestration of iron and exacerbates tumor
      associated anemia.
AB  - The iron-regulatory hormone hepcidin has been proposed as the mediator of anemia
      of inflammation (AI). We examined the acute and chronic effects of hepcidin in
      the mouse. Injections of human hepcidin (50 microg/mouse), but not of its
      diluent, induced hypoferremia within 4 hours. To examine the chronic effects of
      hepcidin, we implanted either tumor xenografts engineered to overexpress human
      hepcidin or control tumor xenografts into nonobese diabetic-severe combined
      immunodeficiency (NOD-SCID) mice. Despite abundant dietary iron, mice with
      hepcidin-producing tumors developed more severe anemia, lower serum iron, and
      increased hepatic iron compared with mice with control tumors. Hepcidin
      contributes to AI by shunting iron away from erythropoiesis and sequestering it
      in the liver, predominantly in hepatocytes.

PMID- 15479722
TI  - Monoclonal antibodies that mimic the action of anti-D in the amelioration of
      murine ITP act by a mechanism distinct from that of IVIg.
AB  - The mechanism of action of intravenous immunoglobulin (IVIg) and polyclonal anti
      D-mediated reversal of immune thrombocytopenia (ITP) is still unclear. However,
      in a murine model of ITP, the therapeutic effect of IVIg appears to be wholly
      dependent upon the expression of the inhibitory Fc receptor, Fc gamma RIIB. We
      previously demonstrated that, similar to anti-D in humans, 2 erythrocyte-reactive
      monoclonal antibodies (TER119 and M1/69) ameliorated murine ITP and inhibited
      reticuloendothelial system (RES) function at doses that protected against
      thrombocytopenia. The current study evaluated the involvement of the inhibitory
      and activating Fc receptors, Fc gamma RIIB and Fc gamma RIIIA, respectively, in
      the TER119 and M1/69-mediated inhibition of thrombocytopenia. In contrast to
      IVIg, in Fc gamma RIIB-deficient mice, both monoclonal antibodies ameliorated ITP
      and both significantly down-regulated the level of expression of the activating
      Fc gamma RIIIA in splenic macrophages. These results indicate that anti
      erythrocyte antibodies that ameliorate ITP act independently of Fc gamma RIIB
      expression but are dependent upon the activating Fc gamma RIIIA.

PMID- 15479723
TI  - Meis1-mediated apoptosis is caspase dependent and can be suppressed by
      coexpression of HoxA9 in murine and human cell lines.
AB  - Coexpression of the homeodomain protein Meis1 and either HoxA7 or HoxA9 is
      characteristic of many acute myelogenous leukemias. Although Meis1 can be
      overexpressed in bone marrow long-term repopulating cells, it is incapable of
      mediating their transformation. Although overexpressing HoxA9 alone transforms
      murine bone marrow cells, concurrent Meis1 overexpression greatly accelerates
      oncogenesis. Meis1-HoxA9 cooperation suppresses several myeloid differentiation
      pathways. We now report that Meis1 overexpression strongly induces apoptosis in a
      variety of cell types in vitro through a caspase-dependent process. Meis1
      requires a functional homeodomain and Pbx-interaction motif to induce apoptosis.
      Coexpressing HoxA9 with Meis1 suppresses this apoptosis and provides protection
      from several apoptosis inducers. Pbx1, another Meis1 cofactor, also induces
      apoptosis; however, coexpressing HoxA9 is incapable of rescuing Pbx-mediated
      apoptosis. This resistance to apoptotic stimuli, coupled with the previously
      reported ability to suppress multiple myeloid differentiation pathways, would
      provide a strong selective advantage to Meis1-HoxA9 coexpressing cells in vivo,
      leading to leukemogenesis.

PMID- 15479725
TI  - De novo generation of CD4 T cells against viruses present in the host during
      immune reconstitution.
AB  - T cells recognizing self-peptides are typically deleted in the thymus by negative
      selection. It is not known whether T cells against persistent viruses (eg,
      herpesviruses) are generated by the thymus (de novo) after the onset of the
      infection. Peptides from such viruses might be considered by the thymus as self
      peptides, and T cells specific for these peptides might be deleted (negatively
      selected). Here we demonstrate in baboons infected with baboon cytomegalovirus
      and baboon lymphocryptovirus (Epstein-Barr virus-like virus) that after
      autologous transplantation of yellow fluorescent protein (YFP)-marked
      hematopoietic cells, YFP+ CD4 T cells against these viruses were generated de
      novo. Thus the thymus generates CD4 T cells against not only pathogens absent
      from the host but also pathogens present in the host. This finding provides a
      strong rationale to improve thymopoiesis in recipients of hematopoietic cell
      transplants and, perhaps, in other persons lacking de novo-generated CD4 T cells,
      such as AIDS patients and elderly persons.

PMID- 15479724
TI  - Butyrate increases the efficiency of translation of gamma-globin mRNA.
AB  - Fetal hemoglobin (Hb F) levels increase in most patients with sickle cell disease
      following intermittent butyrate therapy. Although the full effects of butyrate on
      Hb F levels usually require multiple treatment cycles, in some patients a peak
      level is achieved after a few days of butyrate therapy. Our investigation of the
      mechanism(s) responsible for this rapid induction of Hb F by butyrate showed that
      reticulocyte gamma-globin chain synthesis markedly increased within 24 hours of
      butyrate exposure, without concomitant changes in reticulocyte gamma-globin mRNA
      levels. This suggests that butyrate might induce Hb F by increasing the
      efficiency of translation of gamma-globin mRNA. This hypothesis was confirmed by
      ribosome loading studies that demonstrated enrichment of the polysomal fraction
      of reticulocytes with gamma-globin mRNA following butyrate exposure. Thus, the
      induction of Hb F by butyrate may be mediated by translational effects in
      addition to its well-known effects on transcription of the gamma-globin genes.

PMID- 15479727
TI  - FcRH1: an activation coreceptor on human B cells.
AB  - B-cell activation and differentiation is regulated through the coordinated
      function of a dynamic array of cell surface receptors. At different stages in
      their differentiation, human B cells may express one or more members of a large
      family of immunoglobulin Fc receptor homologs (FcRH) with regulatory potential.
      Among these newly identified transmembrane molecules, FcRH1 is unique in having 2
      immunoreceptor tyrosine-based activation motif (ITAM)-like motifs in its
      intracellular domain. Here we used the Fab fragments of new monoclonal anti-FcRH1
      antibodies and mRNA analysis to evaluate FcRH1 expression and function during B
      cell differentiation. FcRH1 expression begins in pre-B cells, reaches peak levels
      on naive B cells, and is down-regulated after B cells are activated to begin to
      form germinal centers. This FcRH1 down-regulation coincides with dramatic
      enlargement of the pre-germinal center cells, cell cycle entry, and other overt
      signs of activation that include CD80 and CD86 up-regulation and immunoglobulin D
      (IgD) down-regulation. In vitro analysis indicates that ligation of FcRH1 leads
      to its tyrosine phosphorylation and to modest B-cell activation and
      proliferation. Concomitant FcRH1 ligation enhances B-cell antigen receptor (BCR)
      induced Ca(2+) mobilization and proliferation. FcRH1 thus has the potential to
      serve as an activating coreceptor on B cells.

PMID- 15479726
TI  - Regional intravascular delivery of AAV-2-F.IX to skeletal muscle achieves long
      term correction of hemophilia B in a large animal model.
AB  - In earlier work, we showed that adeno-associated virus-mediated delivery of a
      Factor IX gene to skeletal muscle by direct intramuscular injection resulted in
      therapeutic levels of circulating Factor IX in mice. However, achievement of
      target doses in humans proved impractical because of the large number of
      injections required. We used a novel intravascular delivery technique to achieve
      successful transduction of extensive areas of skeletal muscle in a large animal
      with hemophilia. We provide here the first report of long-term (> 3 years, with
      observation ongoing), robust Factor IX expression (circulating levels of 4%-14%)
      by muscle-directed gene transfer in a large animal, resulting in essentially
      complete correction of the bleeding disorder in hemophilic dogs. The results of
      this translational study establish an experimental basis for clinical studies of
      this delivery method in humans with hemophilia B. These findings also have
      immediate relevance for gene transfer in patients with muscular dystrophy.

PMID- 15479728
TI  - Impaired T- and B-cell development in Tcl1-deficient mice.
AB  - TCL1, the overexpression of which may result in T-cell leukemia, is normally
      expressed in early embryonic tissues, the ovary, and lymphoid lineage cells. Our
      analysis of mouse B-lineage cells indicates that Tcl1 expression is initiated in
      pro-B cells and persists in splenic marginal zone and follicular B cells. T
      lineage Tcl1 expression begins in thymocyte progenitors, continues in
      CD4(+)CD8(+) thymocytes, and is extinguished in mature T cells. In Tcl1-deficient
      mice, we found B lymphopoiesis to be compromised at the pre-B cell stage and T
      cell lymphopoiesis to be impaired at the CD4(+)CD8(+) thymocyte stage. A
      corresponding increase was observed in thymocyte susceptibility to anti
      CD3epsilon-induced apoptosis. Reduced numbers of splenic follicular and germinal
      center B cells were accompanied by impaired production of immunoglobulin G1
      (IgG1) and IgG2b antibodies in response to a T-dependent antigen. The marginal
      zone B cells and T-cell-independent antibody responses were also diminished in
      Tcl1(-/-) mice. This analysis indicates a significant role for Tcl1, a
      coactivator of Akt signaling, in normal T- and B-cell development and function.

PMID- 15479729
TI  - Tissue inhibitor of metalloproteinase 1 (TIMP-1) promotes plasmablastic
      differentiation of a Burkitt lymphoma cell line: implications in the pathogenesis
      of plasmacytic/plasmablastic tumors.
AB  - Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a stromal factor with
      multiple functions. Overexpression of TIMP-1 correlates with aggressive clinical
      behavior of a spectrum of tumors. Here, for the first time, we address the role
      of TIMP-1 in the pathogenesis of B-cell lymphomas. An Epstein-Barr virus (EBV)
      negative Burkitt lymphoma cell line with ectopic TIMP-1 expression (TIMP-1JD38)
      was used to identify genes induced/repressed by TIMP-1. Differentially expressed
      genes were analyzed by cDNA microarray, and they were validated by
      immunohistochemistry, flow cytometry, and Western blotting. Analysis revealed
      changes of genes coding for B-cell growth/differentiation, transcription, and
      cell cycle regulators. TIMP-1 repressed expression of germinal center (GC)
      markers CD10, Bcl-6, PAX-5 and up-regulated plasma cell-associated antigens
      CD138, MUM-1/IRF-4, XBP-1, and CD44, suggesting a plasma cell differentiation.
      This is accompanied by activation of signal transducer and activator of
      transcription 3 (STAT-3) and switch to cyclin D2 expression. However, TIMP-1JD38
      cells expressed an inactive form of XBP-1, lacking antibody production/secretion.
      This incomplete plasmacytic differentiation occurs without altering cell
      proliferation, and despite c-Myc deregulation, indicating an arrested
      plasmacytic/plasmablastic stage of differentiation. Further validation in human
      lymphoma cell lines and in primary B-cell tumors demonstrated a predominant TIMP
      1 expression in tumors with plasmacytic/plasmablastic phenotypes, including
      multiple myelomas. These findings strongly support TIMP-1 as an important factor
      in the pathogenesis of plasmacytic/plasmablastic tumors.

PMID- 15479730
TI  - Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not
      CD25+CD4+ Tr cells.
AB  - Dendritic cells (DCs) are specialized antigen-presenting cells that monitor the
      antigenic environment and activate naive T cells. The role of DCs is not only to
      sense danger but also to tolerize the immune system to antigens encountered in
      the absence of maturation/inflammatory stimuli. Indeed, if a naive T cell
      encounters its antigen on immature DCs (iDCs), it may differentiate into a T
      regulatory (Tr) rather than a T-effector cell. However, little is known about the
      mechanisms by which iDCs differentiate Tr cells. We developed a standardized and
      highly reproducible protocol to differentiate Tr cells by repetitive exposure of
      naive peripheral blood CD4(+) T cells to allogeneic iDCs. The resultant Tr cells
      are phenotypically and functionally identical to type 1 Tr (Tr1) cells because
      their generation requires production of IL-10 by iDCs, and they suppress T-cell
      responses through an interleukin-10 (IL-10)- and a transforming growth factor
      beta (TGF-beta)-dependent mechanism. In addition, Tr1 cells induced by iDCs do
      not require the presence of CD4(+)CD25(+) Tr cells for their generation, nor do
      they express high constitutive levels of CD25 or the transcription factor FoxP3.
      Thus, iDCs can drive the differentiation of Tr1 cells and can be used to generate
      large numbers of alloantigen-specific Tr1 cells for clinical use as a cellular
      therapy to restore peripheral tolerance.

PMID- 15479732
TI  - A standardized kinesin nomenclature.
AB  - In recent years the kinesin superfamily has become so large that several
      different naming schemes have emerged, leading to confusion and miscommunication.
      Here, we set forth a standardized kinesin nomenclature based on 14 family
      designations. The scheme unifies all previous phylogenies and nomenclature
      proposals, while allowing individual sequence names to remain the same, and for
      expansion to occur as new sequences are discovered.

PMID- 15479733
TI  - Membrane biogenesis and the unfolded protein response.
AB  - In addition to serving as the entry point for newly translated polypeptides
      making their way through the secretory pathway, the endoplasmic reticulum (ER)
      also synthesizes many lipid components of the entire endomembrane system. A
      report published in this issue implicates a signaling pathway known to respond to
      ER unfolded protein load in the control of phospholipid biosynthesis by the
      organelle (Sriburi et al., 2004). The reasonable notion that demand for ER
      membrane is integrated with protein processing capacity was initially suggested
      by genetic analysis of yeast. The new data lend direct support for this idea and
      imply interesting mechanistic possibilities for how this coupling develops.

PMID- 15479734
TI  - Translation reinitiation at alternative open reading frames regulates gene
      expression in an integrated stress response.
AB  - Stress-induced eukaryotic translation initiation factor 2 (eIF2) alpha
      phosphorylation paradoxically increases translation of the metazoan activating
      transcription factor 4 (ATF4), activating the integrated stress response (ISR), a
      pro-survival gene expression program. Previous studies implicated the 5' end of
      the ATF4 mRNA, with its two conserved upstream ORFs (uORFs), in this
      translational regulation. Here, we report on mutation analysis of the ATF4 mRNA
      which revealed that scanning ribosomes initiate translation efficiently at both
      uORFs and ribosomes that had translated uORF1 efficiently reinitiate translation
      at downstream AUGs. In unstressed cells, low levels of eIF2alpha phosphorylation
      favor early capacitation of such reinitiating ribosomes directing them to the
      inhibitory uORF2, which precludes subsequent translation of ATF4 and represses
      the ISR. In stressed cells high levels of eIF2alpha phosphorylation delays
      ribosome capacitation and favors reinitiation at ATF4 over the inhibitory uORF2.
      These features are common to regulated translation of GCN4 in yeast. The metazoan
      ISR thus resembles the yeast general control response both in its target genes
      and its mechanistic details.

PMID- 15479735
TI  - A role for talin in presynaptic function.
AB  - Talin, an adaptor between integrin and the actin cytoskeleton at sites of cell
      adhesion, was recently found to be present at neuronal synapses, where its
      function remains unknown. Talin interacts with phosphatidylinositol-(4)-phosphate
      5-kinase type Igamma, the major phosphatidylinositol-(4,5)-bisphosphate
      [PI(4,5)P(2)]-synthesizing enzyme in brain. To gain insight into the synaptic
      role of talin, we microinjected into the large lamprey axons reagents that
      compete the talin-PIP kinase interaction and then examined their effects on
      synaptic structure. A dramatic decrease of synaptic actin and an impairment of
      clathrin-mediated synaptic vesicle endocytosis were observed. The endocytic
      defect included an accumulation of clathrin-coated pits with wide necks, as
      previously observed after perturbing actin at these synapses. Thus, the
      interaction of PIP kinase with talin in presynaptic compartments provides a
      mechanism to coordinate PI(4,5)P(2) synthesis, actin dynamics, and endocytosis,
      and further supports a functional link between actin and clathrin-mediated
      endocytosis.

PMID- 15479736
TI  - Hypophosphorylated SR splicing factors transiently localize around active
      nucleolar organizing regions in telophase daughter nuclei.
AB  - Upon completion of mitosis, daughter nuclei assemble all of the organelles
      necessary for the implementation of nuclear functions. We found that upon entry
      into daughter nuclei, snRNPs and SR proteins do not immediately colocalize in
      nuclear speckles. SR proteins accumulated in patches around active nucleolar
      organizing regions (NORs) that we refer to as NOR-associated patches (NAPs),
      whereas snRNPs were enriched at other nuclear regions. NAPs formed transiently,
      persisting for 15-20 min before dissipating as nuclear speckles began to form in
      G1. In the absence of RNA polymerase II transcription, NAPs increased in size and
      persisted for at least 2 h, with delayed localization of SR proteins to nuclear
      speckles. In addition, SR proteins in NAPs are hypophosphorylated, and the SR
      protein kinase Clk/STY colocalizes with SR proteins in NAPs, suggesting that
      phosphorylation releases SR proteins from NAPs and their initial target is
      transcription sites. This work demonstrates a previously unrecognized role of
      NAPs in splicing factor trafficking and nuclear speckle biogenesis.

PMID- 15479737
TI  - COPII-dependent export of cystic fibrosis transmembrane conductance regulator
      from the ER uses a di-acidic exit code.
AB  - Cystic fibrosis (CF) is a childhood hereditary disease in which the most common
      mutant form of the CF transmembrane conductance regulator (CFTR) DeltaF508 fails
      to exit the endoplasmic reticulum (ER). Export of wild-type CFTR from the ER
      requires the coat complex II (COPII) machinery, as it is sensitive to Sar1
      mutants that disrupt normal coat assembly and disassembly. In contrast, COPII is
      not used to deliver CFTR to ER-associated degradation. We find that exit of wild
      type CFTR from the ER is blocked by mutation of a consensus di-acidic ER exit
      motif present in the first nucleotide binding domain. Mutation of the code
      disrupts interaction with the COPII coat selection complex Sec23/Sec24. We
      propose that the di-acidic exit code plays a key role in linking CFTR to the
      COPII coat machinery and is the primary defect responsible for CF in DeltaF508
      expressing patients.

PMID- 15479738
TI  - Yeast Miro GTPase, Gem1p, regulates mitochondrial morphology via a novel pathway.
AB  - Cell signaling events elicit changes in mitochondrial shape and activity.
      However, few mitochondrial proteins that interact with signaling pathways have
      been identified. Candidates include the conserved mitochondrial Rho (Miro) family
      of proteins, which contain two GTPase domains flanking a pair of calcium-binding
      EF-hand motifs. We show that Gem1p (yeast Miro; encoded by YAL048C) is a tail
      anchored outer mitochondrial membrane protein. Cells lacking Gem1p contain
      collapsed, globular, or grape-like mitochondria. We demonstrate that Gem1p is not
      an essential component of characterized pathways that regulate mitochondrial
      dynamics. Genetic studies indicate both GTPase domains and EF-hand motifs, which
      are exposed to the cytoplasm, are required for Gem1p function. Although
      overexpression of a mutant human Miro protein caused increased apoptotic activity
      in cultured cells (Fransson et al., 2003. J. Biol. Chem. 278:6495-6502), Gem1p is
      not required for pheromone-induced yeast cell death. Thus, Gem1p defines a novel
      mitochondrial morphology pathway which may integrate cell signaling events with
      mitochondrial dynamics.

PMID- 15479739
TI  - Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange
      factors.
AB  - The Ras-related GTPase Rap1 stimulates integrin-mediated adhesion and spreading
      in various mammalian cell types. Here, we demonstrate that Rap1 regulates cell
      spreading by localizing guanine nucleotide exchange factors (GEFs) that act via
      the Rho family GTPase Rac1. Rap1a activates Rac1 and requires Rac1 to enhance
      spreading, whereas Rac1 induces spreading independently of Rap1. Active Rap1a
      binds to a subset of Rac GEFs, including VAV2 and Tiam1 but not others such as
      SWAP-70 or COOL-1. Overexpressed VAV2 and Tiam1 specifically require Rap1 to
      promote spreading, even though Rac1 is activated independently of Rap1. Rap1 is
      necessary for the accumulation of VAV2 in membrane protrusions at the cell
      periphery. In addition, if VAV2 is artificially localized to the cell edge with
      the subcellular targeting domain of Rap1a, it increases cell spreading
      independently of Rap1. These results lead us to propose that Rap1 promotes cell
      spreading by localizing a subset of Rac GEFs to sites of active lamellipodia
      extension.

PMID- 15479740
TI  - Adherens junction-dependent and -independent steps in the establishment of
      epithelial cell polarity in Drosophila.
AB  - Adherens junctions (AJs) are thought to be key landmarks for establishing
      epithelial cell polarity, but the origin of epithelial polarity in Drosophila
      remains unclear. Thus, we examined epithelial polarity establishment during early
      Drosophila development. We found apical accumulation of both Drosophila E
      Cadherin (DE-Cad) and the apical cue Bazooka (Baz) as cells first form. Mutant
      analyses revealed that apical Baz accumulations can be established in the absence
      of AJs, whereas assembly of apical DE-Cad complexes requires Baz. Thus, Baz acts
      upstream of AJs during epithelial polarity establishment. During gastrulation the
      absence of AJs results in widespread cell dissociation and depolarization. Some
      epithelial structures are retained, however. These structures maintain apical
      Baz, accumulate apical Crumbs, and organize polarized cytoskeletons, but display
      abnormal cell morphology and fail to segregate the basolateral cue Discs large
      from the apical domain. Thus, although epithelial polarity develops in the
      absence of AJs, AJs play specific roles in maintaining epithelial architecture
      and segregating basolateral cues.

PMID- 15479741
TI  - Requirement of plakophilin 2 for heart morphogenesis and cardiac junction
      formation.
AB  - Plakophilins are proteins of the armadillo family that function in embryonic
      development and in the adult, and when mutated can cause disease. We have ablated
      the plakophilin 2 gene in mice. The resulting mutant mice exhibit lethal
      alterations in heart morphogenesis and stability at mid-gestation (E10.5-E11),
      characterized by reduced trabeculation, disarrayed cytoskeleton, ruptures of
      cardiac walls, and blood leakage into the pericardiac cavity. In the absence of
      plakophilin 2, the cytoskeletal linker protein desmoplakin dissociates from the
      plaques of the adhering junctions that connect the cardiomyocytes and forms
      granular aggregates in the cytoplasm. By contrast, embryonic epithelia show
      normal junctions. Thus, we conclude that plakophilin 2 is important for the
      assembly of junctional proteins and represents an essential morphogenic factor
      and architectural component of the heart.

PMID- 15479742
TI  - Spermidine/spermine N1-acetyltransferase specifically binds to the integrin
      alpha9 subunit cytoplasmic domain and enhances cell migration.
AB  - The integrin alpha9beta1 is expressed on migrating cells, such as leukocytes, and
      binds to multiple ligands that are present at sites of tissue injury and
      inflammation. alpha9beta1, like the structurally related integrin alpha4beta1,
      mediates accelerated cell migration, an effect that depends on the alpha9
      cytoplasmic domain. alpha4beta1 enhances migration through reversible binding to
      the adapter protein, paxillin, but alpha9beta1-dependent migration is paxillin
      independent. Using yeast two-hybrid screening, we identified the polyamine
      catabolizing enzyme spermidine/spermine N(1)-acetyltransferase (SSAT) as a
      specific binding partner of the alpha9 cytoplasmic domain. Overexpression of SSAT
      increased alpha9beta1-mediated migration, and small interfering RNA knockdown of
      SSAT inhibited this migration without affecting cell adhesion or migration that
      was mediated by other integrin cytoplasmic domains. The enzyme activity of SSAT
      is critical for this effect, because a catalytically inactive version did not
      enhance migration. We conclude that SSAT directly binds to the alpha9 cytoplasmic
      domain and mediates alpha9-dependent enhancement of cell migration, presumably by
      localized effects on acetylation of polyamines or of unidentified substrates.

PMID- 15479744
TI  - Incomplete renal tubular acidosis and bone mineral density: a population survey
      in an area of endemic renal tubular acidosis.
AB  - BACKGROUND: 'Primary' osteoporosis has been associated with a high incidence of a
      renal acidification defect, incomplete renal tubular acidosis (iRTA). An acid
      loading test, to exclude the defect, has been recommended for inclusion in the
      work-up of osteoporosis. However, there is no community-based study to confirm
      its utility. METHOD: A community-based survey was conducted in the Khon Kaen
      province, Thailand, between January and June, 2000. We randomly enrolled 361
      apparently healthy adults, 146 men and 215 women, in this study. The bone mineral
      densities (BMDs) of the spine and femur were determined in all subjects. The
      diagnosis of iRTA was based on: normal serum electrolytes and one or both of
      first morning urinary pH >5.5 or the failure of an acid loading test to decrease
      it to >5.5. Dietary diaries, serum electrolyte tests and 24 h urine collections
      were obtained from all iRTA subjects. RESULTS: There were 23 (6.4%) iRTA subjects
      in the population studied. The age, height, weight and calcium intake were
      comparable between iRTA and normal subjects, as were the BMDs of spine and femur.
      There was no difference between the two groups in the distributions of BMD with
      age for either area. Multiple regression analyses of the studied population
      demonstrated that age, body weight, duration of menopause and gender (only for
      the femoral neck) were independent variables that affected BMD. CONCLUSION:
      Incomplete distal renal tubular acidosis alone was not associated with lower bone
      mass in this cohort. It may nevertheless be valuable to monitor serum
      electrolytes and BMD in patients with iRTA due to their tendency to develop
      intermittent metabolic acidosis.

PMID- 15479743
TI  - The syndecan-1 ectodomain regulates alphavbeta3 integrin activity in human
      mammary carcinoma cells.
AB  - The alpha(v)beta(3) integrin participates in cell morphogenesis, growth factor
      signaling, and cell survival. Activation of the integrin is central to these
      processes and is influenced by specific ECM components, which engage both
      integrins and syndecans. This paper demonstrates that the alpha(v)beta(3)
      integrin and syndecan-1 (S1) are functionally coupled. The integrin is dependent
      on the syndecan to become activated and to mediate signals required for MDA-MB
      231 and MDA-MB-435 human mammary carcinoma cell spreading on vitronectin or S1
      specific antibody. Coupling of the syndecan to alpha(v)beta(3) requires the S1
      ectodomain (ED), as ectopic expression of glycosylphosphatidylinositol-linked
      S1ED enhances alpha(v)beta(3) recognition of vitronectin; and treatments that
      target this domain, including competition with recombinant S1ED protein or anti
      S1ED antibodies, mutation of the S1ED, or down-regulation of S1 expression by
      small-interfering RNAs, disrupt alpha(v)beta(3)-dependent cell spreading and
      migration. Thus, S1 is likely to be a critical regulator of many cellular
      behaviors that depend on activated alpha(v)beta(3) integrins.

PMID- 15479745
TI  - Treatment of idiopathic membranoproliferative glomerulonephritis with
      mycophenolate mofetil and steroids.
AB  - BACKGROUND: Treatment of adults with idiopathic membranoproliferative
      glomerulonephritis (IMPGN) is often unrewarding with approximately 60% of
      patients progressing to end-stage renal failure within 10 years. Although
      children with IMPGN may respond to steroid therapy, there is no significant
      benefit to treating adult IMPGN patients with immunosuppression. METHODS: Outcome
      measures in five patients with IMPGN who were treated with oral prednisolone and
      mycophenolate mofetil (MMF) (treatment group) were compared with six patients
      with IMPGN who did not receive immunosuppression (control group). RESULTS: There
      was no significant difference between either group in baseline clinical
      characteristics or systolic and diastolic blood pressure during observation. In
      the treatment group, there was a significant reduction in proteinuria from a
      baseline of 5.09 to 1.97 g/24 h (P = 0.003) at 6 months, 1.96 g/24 h (P = 0.003)
      at 12 months and 2.59 g/24 h (P = 0.015) at 18 months. There was no significant
      change in proteinuria over 18 months in the control group. Serum creatinine
      concentration and creatinine clearance did not change significantly over 18
      months in the treatment group. In the control group, there were significant
      changes in serum creatinine and creatinine clearance over 18 months [baseline 103
      to 159 micromol/l (P = 0.004) and baseline 108 to 67 ml/min (P > 0.001),
      respectively] when compared to baseline, although the differences were not
      significant when the two groups were compared directly. CONCLUSIONS: This
      preliminary study suggests that in the short term, the combination of MMF and
      prednisolone can significantly reduce proteinuria and may preserve renal function
      in patients with IMPGN.

PMID- 15479746
TI  - Laparoscopic live donor nephrectomy.

PMID- 15479747
TI  - Impaired osmoregulation in anorexia nervosa: a case-control study.
AB  - BACKGROUND: Anorexia nervosa (AN) has been associated with abnormal
      osmoregulation and impaired urinary concentrating capacity. Conflicting results
      suggest that the disorder may be related to hypothalamic dysfunction and/or a
      primary renal defect. The role of antidepressants, which are increasingly
      prescribed in AN patients, has not been evaluated. METHODS: We analysed renal
      function as well as electrolyte disturbances and osmoregulation parameters at
      baseline and following a water deprivation test in 12 well-defined AN patients
      (all females, 10 taking antidepressants) vs 12 age-matched controls and 11 young
      female patients taking antidepressants. RESULTS: In comparison with matched
      controls, patients with AN were characterized by a significant alteration of
      osmoregulation both at baseline [lower plasma sodium and osmolality, abnormally
      high levels of antidiuretic hormone (ADH) and tendency towards more concentrated
      urine] and after water deprivation (impaired ADH reaction and lower urinary
      concentrating ability). The AN patients had no electrolyte abnormalities. The two
      patients with the shortest duration of AN showed a normal urinary concentrating
      ability. Patients taking antidepressants showed similar but less marked changes
      than AN patients, including a lower urinary concentrating ability. CONCLUSIONS:
      These results show that AN patients are characterized by abnormal osmoregulation
      at baseline and a lack of reactivity of ADH with a significant urinary
      concentrating defect after water deprivation. The origin of these defects in AN
      patients is probably multifactorial, but the duration of the disease and the
      prescription of antidepressants could play a role.

PMID- 15479748
TI  - Modifiable risk factors for non-adherence to immunosuppressants in renal
      transplant recipients: a cross-sectional study.
AB  - BACKGROUND: Non-adherence to immunosuppressants is a major cause of renal
      transplant failure. Interventions to improve adherence need to target modifiable
      risk factors. METHODS: Adherence was measured using the 'gold standard' measure
      of electronic monitoring in 58 adult renal transplant recipients from a UK
      transplant unit. Subjects were identified from a stratified random sample of 153
      recipients recruited to a larger cross-sectional study comparing different
      measures of adherence. Inclusion criteria included age over 18 years and a
      functioning renal transplant, transplanted 6-63 months previously. Exclusion
      criteria included residence outside the region served by the unit and inability
      to give informed consent. Health beliefs, depression and functional status were
      measured using standardized questionnaires (Beliefs about Medicines
      Questionnaire, Illness Perception Questionnaire, Revised Clinical Interview
      Schedule and SF-36) and semi-structured interview. Transplant and demographic
      details were collected from the notes. RESULTS: Seven [12%, 95% confidence
      interval (CI) 4-20%] subjects missed at least 20% of days medication and 15 (26%,
      15-37%) missed at least 10% of days. Lower belief in the need for medication and
      having a transplant from a live donor were the major factors associated with non
      adherence. Depression was common, although not strongly associated with non
      adherence. CONCLUSIONS: Beliefs about medication are a promising target for
      interventions designed to improve adherence. The lower adherence in recipients of
      transplants from live donors needs confirming but may be clinically important in
      light of the drive to increase live donation.

PMID- 15479749
TI  - Current paradigms about chemokines as therapeutic targets.

PMID- 15479750
TI  - Homocysteine in uraemia--a puzzling and conflicting story.

PMID- 15479751
TI  - Hip dysplasia: a significant risk factor for the development of hip
      osteoarthritis. A cross-sectional survey.
AB  - OBJECTIVES: The aim of this cross-sectional survey of 2232 women and 1336 men
      (age range 20-91 yr) was to investigate individual risk factors for hip joint
      osteoarthritis (OA). METHODS: Standardized, weight-bearing pelvic radiographs
      were evaluated. Radiological hip joint OA was defined as minimum joint space
      width (JSW) </=2.0 mm. Hip dysplasia was evaluated according to common
      radiographic indices. Radiographic findings were correlated to general health and
      lifestyle information obtained at baseline examinations and questionnaires. The
      study focused on age; self-reported hip pain, occupational exposure to repeated
      daily lifting, body mass index, smoking and hip dysplasia. RESULTS: Hip dysplasia
      (HD) prevalence ranged from 5.4-12.8% depending on the radiographic index
      applied. Hip OA prevalence was 1.0-2.5% in subjects <60 yr of age and 4.4-5.3% in
      subjects >/=60 yr of age. Of factors entered into logistic regression analyses,
      only age (P<0.001 for right hips and P<0.001 for left hips) and hip dysplasia
      (P<0.001 for right hips and P = 0.004 for left hips) were significantly
      associated with hip OA prevalence in women. In men, only hip dysplasia was
      associated with hip OA prevalence, P<0.001 in right hips and P = 0.001 in left
      hips. CONCLUSIONS: Of the individual risk factors investigated in this study,
      only age and hip dysplasia were associated with the development of hip
      osteoarthritis.

PMID- 15479752
TI  - Debridement of plantar callosities in rheumatoid arthritis: a randomized
      controlled trial.
AB  - OBJECTIVE: To compare forefoot pain, pressure and function before and after
      normal and sham callus treatment in rheumatoid arthritis (RA). PATIENTS AND
      METHODS: Thirty-eight RA patients were randomly assigned to normal (NCT group) or
      sham (SCT) scalpel debridement. The sham procedure comprised blunt-edged scalpel
      paring of the callus which delivered a physical stimulus but left the
      hyperkeratotic tissue intact, the procedure being partially obscured from the
      patient. Forefoot pain was assessed using a 100 mm visual analogue scale (VAS),
      pressure using a high-resolution foot pressure scanner and function using the
      spatial-temporal gait parameters measured on an instrumented walkway.
      Radiographic scores of joint erosion were obtained for metatarsophalangeal (MTP)
      joints with and without overlying callosities. The trial consisted of a
      randomized sham-controlled phase evaluating the immediate same-day treatment
      effect and an unblinded 4-week follow-up phase. RESULTS: During the sham
      controlled phase, forefoot pain improved in both groups by only 3 points on a VAS
      and no statistically significant between-group difference was found (P = 0.48).
      When data were pooled during the unblinded phase, the improvement in forefoot
      pain reached a peak after 2 days and gradually lessened over the next 28 days.
      Following debridement, peak pressures at the callus sites decreased in the NCT
      group and increased in the SCT group, but there was no statistically significant
      between-group difference (P = 0.16). The area of and duration of contact of the
      callus site on the ground remained unchanged following treatment in both groups.
      Following debridement, walking speed was increased, the stride-length was longer
      and the double-support time shorter in both groups; however, between-group
      differences did not reach levels of statistical significance. MTP joints with
      overlying callus were significantly more eroded than those without (P = 0.02).
      CONCLUSIONS: Treatment of painful plantar callosities in RA using scalpel
      debridement lessened forefoot pain but the effect was no greater than sham
      treatment. Localized pressure or gait function was not significantly improved
      following treatment.

PMID- 15479753
TI  - Inflammatory status and cartilage regenerative potential of synovial fibroblasts
      from patients with osteoarthritis and chondropathy.
AB  - OBJECTIVES: To evaluate the inflammatory status and the cartilage regenerative
      potential of pathological synovial fibroblasts from patients with osteoarthritis
      (OA) compared with non-inflamed synovium (NS)-derived cells from patients with
      chondropathy. METHODS: The inflammatory cell phenotype was investigated based on
      the constitutive and inducible surface expression and secretion of various
      effector molecules using flow cytometry or ELISA assays. The capacity of cells to
      produce cartilage-like extracellular matrix was assessed using acid Alcian blue
      staining and type II collagen immunostaining after treatment with transforming
      growth factor beta1 (TGF-beta1). RESULTS: OA and NS fibroblasts consistently
      expressed CD29, CD44, CD49e, CD54, CD90 and CD106. Expression of high-affinity
      receptors for IL-4, IL-15, CXCL8 and CXCL12 was also detected but only
      intracellularly. All types of fibroblasts spontaneously released abundant amounts
      of CXCL12, CCL2, IL-6 and tissue inhibitor of metalloproteinase 1, while the
      production of IL-11, TGF-beta1, matrix metalloproteinase 1 (MMP-1) and MMP-9 was
      detected at moderate levels. Several other secreted factors remained
      undetectable. No statistically significant differences were noted between the two
      groups of fibroblasts. Treatment with the proinflammatory cytokine tumour
      necrosis factor alpha (TNF-alpha) up-regulated the same set of surface and
      secreted molecules, including CD54, CD106, membrane IL-15, CCL2 and CCL5. Under
      TGF-beta1 treatment and adipogenic culture conditions, both OA and NS fibroblasts
      displayed chondrogenic and adipocytic activities that were reduced in OA compared
      with NS cells. CONCLUSIONS: OA synovial fibroblasts did not display a distinct
      activated inflammatory phenotype compared with NS cells. However, they did differ
      in their reduced ability to produce cartilage-like matrix. This difference may be
      an additional important factor contributing to OA pathogenesis.

PMID- 15479754
TI  - Transforming growth factor beta-1 and gene polymorphisms in oriental ankylosing
      spondylitis.
AB  - OBJECTIVES: To study serum levels of transforming growth factor beta-1 (TGFbeta1)
      and the expression of TGFbeta1 in in vitro peripheral blood mononuclear cell
      (PBMC) cultures in oriental ankylosing spondylitis (AS) patients, and to
      determine their association with codon 10 and 25 TGFB1 gene polymorphisms.
      METHODS: Serum levels of TGFbeta1 were measured by enzyme-linked immunosorbent
      assay (ELISA). The ability of PBMCs to synthesize TGFbeta1 and other cytokines
      was assessed by in vitro cultures stimulated with mitogen. Genomic DNA was
      extracted from PBMCs of AS patients (n=72) or unrelated healthy controls (n=96).
      The codon 10 and 25 polymorphisms in the TGFB1 gene were analysed using standard
      polymerase chain reaction-based methods. RESULTS: AS patients had significantly
      higher serum TGFbeta1 levels than controls (P<0.001). There was no difference in
      the distribution of codon 10 and 25 TGFB1 genotypes between AS patients and
      controls. Incubation of AS and control PBMC with phytohaemagglutinin (PHA) led to
      upregulation of TGFbeta1, interleukin-10, tumour necrosis factor-alpha (TNFalpha)
      and interferon-gamma (IFNgamma) assessed by ELISA. Importantly, PHA-induced
      TGFbeta1 production was significantly enhanced in AS patients compared with
      normal controls whereas the production of the pro-inflammatory cytokines TNFalpha
      and IFNgamma was reduced. CONCLUSIONS: Our results show that AS patients express
      significantly higher levels of serum TGFbeta1 independent of the codon 10 and 25
      genotype. Activation of AS PBMCs led to enhanced TGFbeta1 production accompanied
      by reduction of TNFalpha and IFNgamma while the converse was observed in normal
      controls.

PMID- 15479755
TI  - The measure of our measures.

PMID- 15479756
TI  - Treatment of active psoriatic arthritis with the PPARgamma ligand pioglitazone:
      an open-label pilot study.
AB  - OBJECTIVES: Psoriatic arthritis (PsA) is an inflammatory joint disease, in which
      early neovascularization of affected skin and synovial tissue represents an
      important pathogenetic step in the disease process. Activation of the peroxisome
      proliferator activated receptor gamma (PPARgamma) showed anti-inflammatory
      effects in several in vitro and in vivo models (e.g. collagen-induced arthritis)
      by inhibition of angiogenesis and suppression of proinflammatory cytokines.
      Therefore, we studied the use of pioglitazone, a PPARgamma agonist originally
      developed for the treatment of diabetes, in patients with PsA. METHODS: Ten
      patients with active PsA, seven males and three females, who showed at least two
      tender and two swollen joints despite stable treatment with an NSAID, were
      enrolled in this open-label study. All patients received a daily dose of 60 mg
      pioglitazone while continuing their current NSAID therapy. The primary endpoint
      was the PsARC (Psoriatic Arthritis Response Criterion); the secondary endpoints
      included the ACR20 response and improvement in the Psoriasis Area and Severity
      Index (PASI) in patients with more than 2% skin involvement. Patients were
      evaluated for endpoints at baseline and after 12 weeks. RESULTS: After 12 weeks,
      six of 10 patients met the PsARC. The ACR20 response was achieved in five
      patients. The mean percentage reduction in PASI was 38%, with a clinically
      meaningful PASI 50 response in two of six patients. Median tender joint count
      (interquartile range) decreased from 12.0 (8.0-18.0) to 4.0 (2.0-10.0), and the
      median swollen joint count from 5.0 (4.0-8.0) to 2.0 (1.0-7.0) (P<0.05 for both).
      Median Health Assessment Questionnaire score changed from 1.0 (0.375-1.375) to
      0.75 (0.375-1.0) (P<0.05). Three patients had to be withdrawn from the study due
      to inefficacy and side-effects. Major side-effects were oedema of the lower
      extremities and increase in weight. CONCLUSIONS: Treatment with a PPARgamma
      agonist appears to be a promising therapeutic principle in PsA, but the use of
      PPARgamma ligands might be limited by side-effects such as increase in weight and
      fluid retention.

PMID- 15479757
TI  - A role for mannose-binding lectin dysfunction in generation of autoantibodies in
      systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the possible association of the mannose binding lectin
      (MBL) pathway of complement activation with different disease parameters and
      disease activity in patients with systemic lupus erythematosus (SLE). METHODS:
      MBL genotype, MBL serum concentration, MBL complex activity and MBL pathway
      activity were assessed in 53 patients. The activity of the MBL-MASP complex was
      assessed on the basis of its ability to activate exogenous C4. For MBL pathway
      activity the formation of the terminal complex of complement activation (C5b-9)
      was measured. Results were analysed in relation to clinical variables and
      autoantibody profiles in these patients. RESULTS: MBL complex activity and MBL
      pathway activity were both reduced in patients carrying MBL variant alleles.
      Anticardiolipin and anti-C1q autoantibodies were observed significantly more
      frequently in patients with MBL variant alleles. Furthermore, the presence of
      these autoantibodies was associated with a decreased MBL concentration and
      function. In contrast, anti-MBL autoantibodies were not found in patients with
      MBL variant alleles, possibly related to impaired binding of variant MBL to
      apoptotic material. CONCLUSION: In patients with SLE, a reduced functional
      activity of the MBL pathway of complement, in relation to expression of MBL
      variant alleles, is associated with increased levels of autoantibodies against
      cardiolipin and C1q, but not against MBL. We hypothesize that an enhanced
      production of autoantibodies may be related to disturbed clearance of apoptotic
      material due to impaired MBL function.

PMID- 15479758
TI  - National Academy of Sciences endorses National Institutes of Health plan for
      enhanced access to research information.

PMID- 15479759
TI  - Biography of Arthur L. Horwich.

PMID- 15479760
TI  - The oncogenic potential of autocrine human growth hormone in breast cancer.

PMID- 15479761
TI  - Counting the cost of a cold-blooded life: metabolomics of cold acclimation.

PMID- 15479762
TI  - Smallpox: an ancient disease enters the modern era of virogenomics.

PMID- 15479764
TI  - Ringwoodite lamellae in olivine: Clues to olivine-ringwoodite phase transition
      mechanisms in shocked meteorites and subducting slabs.
AB  - The first natural occurrence of ringwoodite lamellae was found in the olivine
      grains inside and in areas adjacent to the shock veins of a chondritic meteorite,
      and these lamellae show distinct growth mechanism. Inside the veins where
      pressure and temperature were higher than elsewhere, ringwoodite lamellae formed
      parallel to the [101] planes of olivine, whereas outside they lie parallel to the
      (100) plane of olivine. The lamellae replaced the host olivine from a few percent
      to complete. Formation of these lamellae relates to a diffusion-controlled growth
      of ringwoodite along shear-induced planar defects in olivine. The planar defects
      and ringwoodite lamellae parallel to the [101] planes of olivine should have been
      produced in higher shear stress and temperature region than that parallel to the
      (100) plane of olivine. This study suggests that the time duration of high
      pressure and temperature for the growth of ringwoodite lamellae might have lasted
      at least for several seconds, and that an intracrystalline transformation
      mechanism of ringwoodite in olivine could favorably operate in the subducting
      lithospheric slabs in the deep Earth.

PMID- 15479763
TI  - Substrate polypeptide presents a load on the apical domains of the chaperonin
      GroEL.
AB  - A conundrum has arisen in the study of the structural states of the GroEL-GroES
      chaperonin machine: When either ATP or ADP is added along with GroES to GroEL,
      the same asymmetric complex, with one ring in a GroES-domed state, is observed by
      either x-ray crystallographic study or cryoelectron microscopy. Yet only
      ATP/GroES can trigger productive folding inside the GroES-encapsulated cis cavity
      by ejecting bound polypeptide from hydrophobic apical binding sites during
      attendant rigid body elevation and twisting of these domains. Here, we show that
      this difference occurs because polypeptide substrate in fact presents a load on
      the apical domains, and, although ATP can counter this load effectively, ADP
      cannot. We monitored apical domain movement in real time by fluorescence
      resonance energy transfer (FRET) between a fixed equatorial fluorophore and one
      attached to the mobile apical domain. In the absence of bound polypeptide,
      addition of either ATP/GroES or ADP/GroES to GroEL produced the same rapid rate
      and extent of decrease of FRET (t(1/2) < 1 sec), reflecting similarly rapid
      apical movement to the same end-state and explaining the results of the
      structural studies, which were all carried out in the absence of substrate
      polypeptide. But in the presence of bound malate dehydrogenase or rhodanese,
      whereas similar rapid and extensive FRET changes were observed with ATP/GroES,
      the rate of FRET change with ADP/GroES was slowed by >100-fold and the extent of
      change was reduced, indicating that the apical domains opened in a slow and
      partial fashion. These results indicate that the free energy of gamma-phosphate
      binding, measured earlier as 43 kcal per mol (1 cal = 4.184 J) of rings, is
      required for driving the forceful excursion or "power stroke" of the apical
      domains needed to trigger release of the polypeptide load into the central
      cavity.

PMID- 15479765
TI  - Shape control through molecular segregation in giant surfactant aggregates.
AB  - Mixtures of cationic and anionic surfactants crystallized at various ratios in
      the absence of added salt form micrometer-sized colloids. Here, we propose and
      test a general mechanism explaining how this ratio controls the shape of the
      resulting colloidal structure, which can vary from nanodiscs to punctured planes;
      during cocrystallization, excess (nonstoichiometric) surfactant accumulates on
      edges or pores rather than being incorporated into crystalline bilayers.
      Molecular segregation then produces a sequence of shapes controlled by the
      initial mole ratio only. Using freeze-fracture electron microscopy, we identified
      three of these states and their corresponding coexistence regimes. Fluorescence
      confocal microscopy directly showed the segregation of anionic and cationic
      components within the aggregate. The observed shapes are consistently reproduced
      upon thermal cycling, demonstrating that the icosahedral shape corresponds to the
      existence of a local minimum of bending energy for facetted icosahedra when the
      optimal amount of excess segregated material is present.

PMID- 15479766
TI  - VEGF is required for the maintenance of dorsal root ganglia blood vessels but not
      neurons during development.
AB  - Vascular endothelial growth factor (VEGF) is a potent regulator of vascular
      function through its control of multiple endothelial cell functions. In addition
      to its key role in vascularization, VEGF has recently been shown to have
      neurotrophic activity during hypoxic stress. In the central and peripheral motor
      nervous system, VEGF treatment increased neuronal vascularization and perfusion,
      as well as having direct trophic effects on neurons and Schwann cells. However,
      the role of VEGF in the sensory nervous system remains unclear. To characterize
      the differential effects of VEGF on endothelial cells and neurons in sensory
      ganglia, we used explanted mouse dorsal root ganglia (DRG), a culture system
      containing neurons and endothelial cells in close apposition. We show that VEGF
      is expressed by neurons and satellite cells, but not by endothelial cells or
      pericytes. On the other hand, the tyrosine kinase VEGF receptor VEGFR-2 was
      robustly expressed by endothelial cells throughout the extensive DRG capillary
      network, but not found at either the transcript or protein level in sensory
      neurons or other nonendothelial cells of the DRG. Both soluble receptor
      sequestration of VEGF and small molecule kinase inhibition of VEGFR-2 signaling
      rapidly disrupted the connectivity, branching, and structural integrity of the
      capillary network of embryonic DRG; this effect was no longer evident
      postnatally. However, VEGF inhibition showed no detectable effect on neuronal
      health at any stage analyzed. These data suggest that endogenous VEGF is a strict
      requirement for vascular, but not neuronal, maintenance in developing sensory
      ganglia.

PMID- 15479768
TI  - Over-the-counter cough and cold medicines: should parents be using them for their
      children?

PMID- 15479767
TI  - Amino acids and leucine allow insulin activation of the PKB/mTOR pathway in
      normal adipocytes treated with wortmannin and in adipocytes from db/db mice.
AB  - Amino acids are nutrients responsible for mammalian target of rapamycin (mTOR)
      regulation in mammalian cells. The mTOR protein is mainly known for its role in
      regulating cell growth, notably via protein synthesis. In addition to amino
      acids, mTOR is regulated by insulin via a phosphatidylinositol 3-kinase (PI 3
      kinase)-dependent pathway. mTOR mediates crosstalk between amino acids and
      insulin signaling. We show that in freshly isolated rat adipocytes, insulin
      stimulates the phosphorylation of mTOR on serine 2448, a protein kinase B (PKB)
      consensus phosphorylation site. This site is also phosphorylated by amino acids,
      which in contrast to insulin do not activate PKB. Moreover, insulin and amino
      acids have an additive effect on mTOR phosphorylation, indicating that they act
      via two independent pathways. Importantly, amino acids, notably leucine, permit
      insulin to stimulate PKB when PI 3-kinase is inhibited. They also rescue glucose
      transport and the mTOR pathway. Further, leucine alone can improve insulin
      activation of PKB in db/db mice. Our results define the importance of amino acids
      in insulin signaling and reveal leucine as a key amino acid in disease situations
      associated with insulin-resistance in adipocytes.

PMID- 15479769
TI  - Transient ischemic attack secondary to hypertensive crisis related to Panax
      ginseng.

PMID- 15479770
TI  - Population-based medication reviews: a descriptive analysis of the medication
      issues identified in a medicare not-for-profit prescription discount program.
AB  - BACKGROUND: Medication reviews may be an important strategy to improve medication
      use, especially for individuals receiving many drugs. OBJECTIVE: To describe the
      types of medication issues and recommendations identified in the Iowa Priority
      Brown Bag Medication Reviews, compare individuals with medication issues with
      those without medication issues, and describe Iowa Priority enrollees'
      experiences with and satisfaction of the review. METHODS: A retrospective review
      of enrollment forms and medication review records and a survey of Iowa Priority
      members were conducted in 2002. Subjects were Medicare-eligible individuals who
      joined the Iowa Priority Prescription Savings Program. Frequency distributions
      and descriptive statistics were calculated. Analysis using t-test and chi(2) test
      determined differences between individuals with and without issues regarding use
      of drug therapy. RESULTS: Almost 13% of Iowa Priority enrollees received a
      review. There were 1167 individuals with 2123 medication issues identified.
      Nonprescription medications accounted for one-third of drug interactions and >40%
      of duplications. People with issues had poorer health, more chronic conditions,
      and took more drugs than people without medication issues. One-third of survey
      respondents discussed the review with their physicians, and 17.7% reported
      medication changes. Satisfaction with the review was good; however, only 24% were
      likely to have received an annual review. CONCLUSIONS: Iowa Priority Brown Bag
      Medication Reviews showed that individuals with fair/poor health, higher numbers
      of medications, and more chronic conditions were likely to have medication
      issues. Reviews generated discussions between physicians and patients, produced
      some medication changes, and helped individuals save money.

PMID- 15479771
TI  - September 11th anniversary: revisiting the damage beyond Ground Zero.

PMID- 15479772
TI  - Pharmacologic perspectives for once-daily antiretroviral therapy.
AB  - OBJECTIVE: To contrast available once-daily antiretroviral agents and
      combinations of these agents from a clinical pharmacologic viewpoint. DATA
      SOURCES: Data were extracted from publications and major HIV conference
      proceedings cited in MEDLINE (1966-March 2004) using the search terms
      antiretroviral therapy, combination therapy, once-daily therapy, and
      pharmacokinetics. Additional references were obtained from the bibliographies of
      these sources. STUDY SELECTION AND DATA EXTRACTION: Information pertaining to
      pharmacologic perspectives for once-daily antiretroviral agents was selected.
      DATA SYNTHESIS: Maximal and durable suppression of plasma HIV RNA, the principal
      goal of therapy, depends on the intrinsic antiviral activity of the
      antiretroviral regimen. A favorable tolerability/toxicity profile is also
      fundamentally important. All once-daily agents exhibit some pharmacologic
      limitations or lack adequate long-term follow-up. Of available agents, efavirenz
      has a long and distinguished efficacy record, with reasonable safety and moderate
      tolerability. Lamivudine, and newer agents such as atazanavir (or
      atazanavir/ritonavir), emtricitabine, fosamprenavir/ritonavir, and tenofovir, may
      offer pharmacologic advantages in the current state of once-daily therapy.
      Important considerations exist for coadministering once-daily agents including
      drug-drug interactions, drug-food incompatibilities, and synergistic toxicities.
      Few controlled studies have compared once-daily regimens with conventional
      regimens. CONCLUSIONS: Progress has been made toward once-daily therapy, but more
      clinical experience with available agents is needed, including comparative
      studies of entirely once-daily regimens versus conventional regimens. Limitations
      of currently available agents signify a need for improved antiretroviral
      utilization or new alternative agents.

PMID- 15479773
TI  - Patient and physician attitudes to using medications with religiously forbidden
      ingredients.
AB  - BACKGROUND: Over 1000 medications contain pork- and/or beef-derived gelatin and
      stearic acid as inert ingredients. Use of these medications in patients with
      religious beliefs against consumption of these ingredients might constitute an
      ethical conflict. OBJECTIVE: To assess patients' and physicians' attitudes about
      using medications with religiously prohibited ingredients derived from pork
      and/or beef. METHODS: In this pilot study, 100 patients and 100 physicians
      completed a survey designed to assess their knowledge and opinion on using
      medications that might contain inert ingredients derived from animals whose
      consumption offends followers of certain religions. RESULTS: Of the 100 patients
      surveyed, most (84%) reported that they were not aware that several medications
      contained ingredients derived from pork and/or beef. About 63% of the patients
      wanted their physicians, and 35% of the patients wanted their non-physician
      healthcare providers (pharmacists, nurses), to inform them when using such
      medications. Thirteen percent of the patients shared religious reasons for not
      consuming pork and/or beef products. Approximately 70% of physicians were unaware
      that several medications contain ingredients that might be against their
      patients' religion, and most (70%) thought that it was important to inform their
      patients if such drugs were prescribed. CONCLUSIONS: This pilot study suggests
      that both patients and physicians think that patients should be informed whenever
      medications that contain pork- and/or beef-derived products are prescribed. The
      use of medications with these ingredients is an ethical issue. Informing patients
      about this issue promotes respect for their religious beliefs and may promote
      therapeutic alliance; therefore, this might have public health implications and
      needs further research.

PMID- 15479774
TI  - Insulin strategies for type 2 diabetes mellitus.
AB  - OBJECTIVE: To review the currently available insulin analogs and the benefits of
      insulin therapy in the treatment of type 2 diabetes mellitus. DATA SOURCES: A
      MEDLINE search (1990-March 2004) was conducted using insulin and type 2 diabetes
      mellitus as search terms to identify clinical trials and review articles. The
      bibliographies of identified articles were reviewed. STUDY SELECTION AND DATA
      EXTRACTION: All articles identified from the data sources were evaluated and
      deemed relevant if they included and assessed clinical outcomes. DATA SYNTHESIS:
      Since its discovery in 1922, insulin therapy has been the only available
      pharmacologic treatment for type 1 diabetes and a mainstay therapy for patients
      with type 2 diabetes who fail to obtain glycemic control with oral antidiabetic
      agents. This article reviews the current insulin analogs available on the market
      and insulin regimens that are designed to mimic the pancreatic beta-cells'
      response to a glucose load. CONCLUSIONS: Insulin therapy is often withheld until
      late in the disease process for patients with type 2 diabetes mellitus. This
      results in an enormous burden of disease for patients. Insulin therapy is
      beneficial in obtaining glycemic control and may attenuate the complications
      associated with diabetes.

PMID- 15479775
TI  - Efficacy of acetylcholinesterase inhibitors in frontotemporal dementia.

PMID- 15479776
TI  - Possible reduction in posttraumatic stress disorder symptoms with oxcarbazepine
      in a patient with bipolar disorder.
AB  - OBJECTIVE: To report the effect of oxcarbazepine in a patient with bipolar
      illness and posttraumatic stress disorder (PTSD). CASE SUMMARY: A 38-year-old
      white woman with PTSD and bipolar disorder who had partially responded to
      carbamazepine was treated with oxcarbazepine. Within a month of initiation of
      treatment with oxcarbazepine, she reported progressive improvement in her PTSD
      symptoms. As oxcarbazepine monotherapy with 750 mg twice daily continued, she
      reported significant reduction of her PTSD symptoms and stabilization of her
      mood. She tolerated oxcarbazepine without adverse effects. DISCUSSION: PTSD
      symptoms tend to wax and wane. Spontaneous remission also occurs in some patients
      with PTSD. There are a few reports indicating that carbamazepine alleviates PTSD
      symptoms. Since oxcarbazepine is an analog of carbamazepine, it is theorized that
      oxcarbazepine also has efficacy in significantly reducing PTSD symptoms.
      CONCLUSIONS: There are case reports and uncontrolled studies suggesting that
      antiepileptic drugs (AEDs) alleviate PTSD symptoms. Oxcarbazepine may also
      benefit patients with PTSD. However, controlled studies are needed to investigate
      the use of AEDs in patients with PTSD and bipolar disorder.

PMID- 15479777
TI  - Single high-dose rectal acetaminophen in children.
AB  - OBJECTIVE: To determine whether there is sufficient evidence to support the use
      of one-time high-dose (>30 mg/kg) rectally administered acetaminophen to control
      postoperative pain in children. DATA SOURCES: Literature was accessed through
      MEDLINE (1966-May 2004) and bibliographic searches. STUDY SELECTION AND DATA
      EXTRACTION: All articles identified from the data sources were evaluated and all
      studies regarding the use of greater than 30 mg/kg of acetaminophen in children
      were included for this review. DATA SYNTHESIS: A single high dose of rectally
      administered acetaminophen has been used in children to control postoperative
      pain. Ten randomized controlled trials and pharmacokinetic studies evaluating the
      use of greater than 30 mg/kg of rectally administered acetaminophen in children
      were identified and reviewed. Each study had a unique objective. The studies also
      differed substantially in regard to design, study population, dosing, rectal
      formulation used, and monitoring. CONCLUSIONS: Due to limited study data, wide
      study variability, and lack of standardization in terms of design, objectives,
      study population, dosing, rectal formulation, and monitoring, compounded by the
      fact that children often require additional doses of acetaminophen to control
      postoperative pain, the practice of using one-time, high-dose, rectally
      administered acetaminophen in children cannot be recommended at this time.

PMID- 15479778
TI  - Calcimimetics and the treatment of primary and secondary hyperparathyroidism.
AB  - OBJECTIVE: To review the mechanism of action, development, and clinical
      application of the calcimimetic compounds being investigated for the treatment of
      primary and secondary hyperparathyroidism (HPT). DATA SOURCES: A MEDLINE search
      (1990-April 2004) was performed to identify all published articles related to
      calcimimetics. Published abstracts over the previous 5 years from various
      scientific meetings (American Society of Nephrology, American Society for
      Clinical Pharmacology and Therapeutics, American Society of Bone and Mineral
      Research) were also searched for reports regarding investigational calcimimetic
      agents. Data on cinacalcet HCl were provided by Amgen, Inc. STUDY SELECTION AND
      DATA EXTRACTION: Studies were selected based on number of patients included,
      relevance to the approved indications, and inclusion of pharmacokinetic and drug
      interaction information. DATA SYNTHESIS: The investigational calcimimetic
      compounds directly modulate the calcium-sensing receptor and can produce at least
      a 30% reduction in parathyroid hormone (PTH) secretion in secondary HPT.
      Cinacalcet appears to have more predictable pharmacokinetics and a lower risk of
      symptomatic hypocalcemia than the older agent, R-568. The safety profile and
      effective reduction in PTH and simultaneous reductions in calcium and phosphorus
      (and the calcium-phosphorus product) induced by cinacalcet make this agent
      advantageous over previously used therapies, such as vitamin D and phosphate
      binding agents. More studies are required to determine additional uses of
      cinacalcet. CONCLUSIONS: Cinacalcet has a unique mechanism for reducing PTH
      concentration and appears to be a safe and effective oral therapy for both
      primary and secondary HPT.

PMID- 15479779
TI  - Comparing hyperlipidemia control with daily versus twice-weekly simvastatin.
AB  - BACKGROUND: Costs associated with the use of hydroxymethylglutaryl coenzyme A
      reductase inhibitors are increasing. Finding ways to manage hyperlipidemia at
      lower costs is critical to all healthcare systems. OBJECTIVE: To assess
      effectiveness, safety, cost, and patients' satisfaction when converting
      hyperlipemic patients taking simvastatin daily to simvastatin twice weekly.
      METHODS: This nonrandomized, open-label, proof-of-concept study converted
      patients treated with simvastatin 10 or 20 mg daily to 40 or 80 mg twice weekly,
      respectively, for 12 weeks. The lipid profiles at enrollment, week 6, and week 12
      were compared using repeated-measures ANOVA. The percentage of patients attaining
      the appropriate low-density lipoprotein cholesterol (LDL-C) goal was determined.
      RESULTS: Thirty-one patients completed the study. The proportion of patients at
      the LDL-C goal was not statistically different between enrollment and week 12
      (87% vs 68%; p = 0.068). The mean LDL-C value +/- SD at weeks 6 and 12 increased
      compared with enrollment (112 +/-20, 111 +/-17, and 97 +/- 17 mg/dL,
      respectively; p < 0.001). Three (10%) patients reported nonadherence to the twice
      weekly regimen. Seventeen (55%) patients reported that both regimens were equally
      convenient or preferred the twice-weekly regimen. Estimated cost-savings at our
      institution associated with this regimen would be $32 000 per 1000 patients per
      year. CONCLUSIONS: The twice-weekly regimen safely maintained most of the
      patients at their LDL-C goal level, and over half the patients found this regimen
      to be the same or easier to follow than a daily regimen. Large outcome studies
      evaluating this approach are needed.

PMID- 15479780
TI  - Development, implementation, and evaluation of a community pharmacy-based asthma
      care model.
AB  - BACKGROUND: Pharmacists are uniquely placed in the healthcare system to address
      critical issues in asthma management in the community. Various programs have
      shown the benefits of a pharmacist-led asthma care program; however, no such
      programs have previously been evaluated in Australia. OBJECTIVE: To measure the
      impact of a specialized asthma service provided through community pharmacies in
      terms of objective patient clinical, humanistic, and economic outcomes. METHODS:
      A parallel controlled design, where 52 intervention patients and 50 control
      patients with asthma were recruited in 2 distinct locations, was used. In the
      intervention area, pharmacists were trained and delivered an asthma care model,
      with 3 follow-up visits over 6 months. This model was evaluated based on
      clinical, humanistic, and economic outcomes compared between and within groups.
      RESULTS: There was a significant reduction in asthma severity in the intervention
      group, 2.6 +/- 0.5 to 1.6 +/- 0.7 (mean +/- SD; p < 0.001) versus the control
      group, 2.3 +/- 0.7 to 2.4 +/- 0.5. In the intervention group, peak flow indices
      improved from 82.7% +/- 8.2% at baseline to 87.4% +/- 8.9% (p < 0.001) at the
      final visit, and there was a significant reduction in the defined daily dose of
      albuterol used by patients, from 374.8 +/- 314.8 microg at baseline to 198.4 +/-
      196.9 microg at the final visit (p < 0.015). There was also a statistically
      significant improvement in perceived control of asthma and asthma-related
      knowledge scores in the intervention group compared with the control group
      between baseline and the final visit. Annual savings of $132.84(AU) in medication
      costs per patient and $100,801.20 for the whole group, based on overall severity
      reduction, were demonstrated. CONCLUSIONS: Based on the results of this study, it
      appears that a specialized asthma care model offers community pharmacists an
      opportunity to contribute toward improving asthma management in the Australian
      community.

PMID- 15479781
TI  - Substrate recognition and catalysis by the Holliday junction resolving enzyme
      Hje.
AB  - Two archaeal Holliday junction resolving enzymes, Holliday junction cleavage
      (Hjc) and Holliday junction endonuclease (Hje), have been characterized. Both are
      members of a nuclease superfamily that includes the type II restriction enzymes,
      although their DNA cleaving activity is highly specific for four-way junction
      structure and not nucleic acid sequence. Despite 28% sequence identity, Hje and
      Hjc cleave junctions with distinct cutting patterns--they cut different strands
      of a four-way junction, at different distances from the junction centre. We
      report the high-resolution crystal structure of Hje from Sulfolobus solfataricus.
      The structure provides a basis to explain the differences in substrate
      specificity of Hje and Hjc, which result from changes in dimer organization, and
      suggests a viral origin for the Hje gene. Structural and biochemical data support
      the modelling of an Hje:DNA junction complex, highlighting a flexible loop that
      interacts intimately with the junction centre. A highly conserved serine residue
      on this loop is shown to be essential for the enzyme's activity, suggesting a
      novel variation of the nuclease active site. The loop may act as a conformational
      switch, ensuring that the active site is completed only on binding a four-way
      junction, thus explaining the exquisite specificity of these enzymes.

PMID- 15479783
TI  - Empirical evaluation of data transformations and ranking statistics for
      microarray analysis.
AB  - There are many options in handling microarray data that can affect study
      conclusions, sometimes drastically. Working with a two-color platform, this study
      uses ten spike-in microarray experiments to evaluate the relative effectiveness
      of some of these options for the experimental goal of detecting differential
      expression. We consider two data transformations, background subtraction and
      intensity normalization, as well as six different statistics for detecting
      differentially expressed genes. Findings support the use of an intensity-based
      normalization procedure and also indicate that local background subtraction can
      be detrimental for effectively detecting differential expression. We also verify
      that robust statistics outperform t-statistics in identifying differentially
      expressed genes when there are few replicates. Finally, we find that choice of
      image analysis software can also substantially influence experimental
      conclusions.

PMID- 15479784
TI  - Repair of U/G and U/A in DNA by UNG2-associated repair complexes takes place
      predominantly by short-patch repair both in proliferating and growth-arrested
      cells.
AB  - Nuclear uracil-DNA glycosylase UNG2 has an established role in repair of U/A
      pairs resulting from misincorporation of dUMP during replication. In antigen
      stimulated B-lymphocytes UNG2 removes uracil from U/G mispairs as part of somatic
      hypermutation and class switch recombination processes. Using antibodies specific
      for the N-terminal non-catalytic domain of UNG2, we isolated UNG2-associated
      repair complexes (UNG2-ARC) that carry out short-patch and long-patch base
      excision repair (BER). These complexes contain proteins required for both types
      of BER, including UNG2, APE1, POLbeta, POLdelta, XRCC1, PCNA and DNA ligase, the
      latter detected as activity. Short-patch repair was the predominant mechanism
      both in extracts and UNG2-ARC from proliferating and less BER-proficient growth
      arrested cells. Repair of U/G mispairs and U/A pairs was completely inhibited by
      neutralizing UNG-antibodies, but whereas added recombinant SMUG1 could partially
      restore repair of U/G mispairs, it was unable to restore repair of U/A pairs in
      UNG2-ARC. Neutralizing antibodies to APE1 and POLbeta, and depletion of XRCC1
      strongly reduced short-patch BER, and a fraction of long-patch repair was POLbeta
      dependent. In conclusion, UNG2 is present in preassembled complexes proficient in
      BER. Furthermore, UNG2 is the major enzyme initiating BER of deaminated cytosine
      (U/G), and possibly the sole enzyme initiating BER of misincorporated uracil
      (U/A).

PMID- 15479782
TI  - 'Conserved hypothetical' proteins: prioritization of targets for experimental
      study.
AB  - Comparative genomics shows that a substantial fraction of the genes in sequenced
      genomes encodes 'conserved hypothetical' proteins, i.e. those that are found in
      organisms from several phylogenetic lineages but have not been functionally
      characterized. Here, we briefly discuss recent progress in functional
      characterization of prokaryotic 'conserved hypothetical' proteins and the
      possible criteria for prioritizing targets for experimental study. Based on these
      criteria, the chief one being wide phyletic spread, we offer two 'top 10' lists
      of highly attractive targets. The first list consists of proteins for which
      biochemical activity could be predicted with reasonable confidence but the
      biological function was predicted only in general terms, if at all ('known
      unknowns'). The second list includes proteins for which there is no prediction of
      biochemical activity, even if, for some, general biological clues exist ('unknown
      unknowns'). The experimental characterization of these and other 'conserved
      hypothetical' proteins is expected to reveal new, crucial aspects of microbial
      biology and could also lead to better functional prediction for medically
      relevant human homologs.

PMID- 15479785
TI  - Non-hypoxic transcriptional activation of the aryl hydrocarbon receptor nuclear
      translocator in concert with a novel hypoxia-inducible factor-1alpha isoform.
AB  - Aryl hydrocarbon receptor nuclear translocator (ARNT) belongs to the basic helix
      loop-helix Per-Arnt-Sim (bHLH PAS) protein which dimerizes with other PAS
      proteins. Although it has a transactivation domain (TAD), ARNT functions as an
      assistant partner of main factors, such as aryl hydrocarbon receptor and hypoxia
      inducible factors, rather than acting as a straightforward transcription factor.
      However, ARNT may function as an active transcription factor using its TAD either
      in association with itself, single-minded protein 1, or trachealess protein. In
      the present study, we identified a novel ARNT partner, a HIF-1alpha variant,
      which is ubiquitously expressed in human tissues and cancer cell lines. The HIF
      1alpha variant, designated HIF-1alpha417, bound to ARNT and, moreover, stimulated
      the transcription of the erythropoietin enhancer reporter gene. This stimulation
      was markedly augmented by ARNT but not by the ARNT603 mutant lacking the TAD.
      Thus, augmentation by ARNT suggests that ARNT determined the transcriptional
      activity. HIF-1alpha417 was found to be associated with ARNT and to bind to the
      hypoxia response element containing the E-box core. Moreover, HIF-1alpha417
      promoted the nuclear translocation of ARNT, and conversely ARNT stabilized HIF
      1alpha417. Taken together, our results suggest that HIF-1alpha417 is a novel
      partner that is required for transcription activity of ARNT.

PMID- 15479786
TI  - The A2453-C2499 wobble base pair in Escherichia coli 23S ribosomal RNA is
      responsible for pH sensitivity of the peptidyltransferase active site
      conformation.
AB  - Peptide bond formation, catalyzed by the ribosomal peptidyltransferase, has long
      been known to be sensitive to monovalent cation concentrations and pH. More
      recently, we and others have shown that residue A2451 in the peptidyltransferase
      center of the Escherichia coli 50S ribosomal subunit changes conformation in
      response to alterations in pH, depending on ionic conditions and temperature. Two
      wobble pairs, A2453-C2499 and A2450-C2063, have been proposed as potential
      candidates to convey pH-dependent flexibility to the peptidyltransferase center.
      Each is presumed to possess a near-neutral pK(a), and both lie in proximity to
      A2451. We show through mutagenesis and chemical probing that the identity of the
      A2453-C2499 base pair, but not the A2450-C2063 base pair, is critical for the pH
      dependent structural rearrangement of A2451. We conclude that, while the A2453
      C2499 base pair may be important for maintaining the structure of the active site
      in the E.coli peptidyltransferase center, its lack of conservation makes it, and
      consequently its near-neutral pK(a), unlikely to contribute to function during
      peptide bond formation.

PMID- 15479787
TI  - Electrostatic analysis of the hepatitis C virus NS3 helicase reveals both active
      and allosteric site locations.
AB  - Multi-conformation continuum electrostatics (MCCE) was used to analyze various
      structures of the NS3 RNA helicase from the hepatitis C virus in order to
      determine the ionization state of amino acid side chains and their pK(a)s. In
      MCCE analyses of HCV helicase structures that lacked ligands, several active site
      residues were identified to have perturbed pK(a)s in both the nucleic acid
      binding site and in the distant ATP-binding site, which regulates helicase
      movement. In all HCV helicase structures, Glu493 was unusually basic and His369
      was abnormally acidic. Both these residues are part of the HCV helicase nucleic
      acid binding site, and their roles were analyzed by examining the pH profiles of
      site-directed mutants. Data support the accuracy of MCCE predicted pK(a) values,
      and reveal that Glu493 is critical for low pH enzyme activation. Several key
      residues, which were previously shown to be involved in helicase-catalyzed ATP
      hydrolysis, were also identified to have perturbed pK(a)s including Lys210 in the
      Walker-A motif and the DExD/H-box motif residues Asp290 and His293. When DNA was
      present in the structure, the calculated pK(a)s shifted for both Lys210 and
      Asp290, demonstrating how DNA binding might lead to electrostatic changes that
      stimulate ATP hydrolysis.

PMID- 15479789
TI  - Nuclear heat shock response and novel nuclear domain 10 reorganization in
      respiratory syncytial virus-infected a549 cells identified by high-resolution two
      dimensional gel electrophoresis.
AB  - The pneumovirus respiratory syncytial virus (RSV) is a leading cause of epidemic
      respiratory tract infection. Upon entry, RSV replicates in the epithelial
      cytoplasm, initiating compensatory changes in cellular gene expression. In this
      study, we have investigated RSV-induced changes in the nuclear proteome of A549
      alveolar type II-like epithelial cells by high-resolution two-dimensional gel
      electrophoresis (2DE). Replicate 2D gels from uninfected and RSV-infected nuclei
      were compared for changes in protein expression. We identified 24 different
      proteins by peptide mass fingerprinting after matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MS), whose average normalized spot
      intensity was statistically significant and differed by +/-2-fold. Notable among
      the proteins identified were the cytoskeletal cytokeratins, RNA helicases,
      oxidant-antioxidant enzymes, the TAR DNA binding protein (a protein that
      associates with nuclear domain 10 [ND10] structures), and heat shock protein 70-
      and 60-kDa isoforms (Hsp70 and Hsp60, respectively). The identification of Hsp70
      was also validated by liquid chromatography quadropole-TOF tandem MS (LC-MS/MS).
      Separate experiments using immunofluorescence microscopy revealed that RSV
      induced cytoplasmic Hsp70 aggregation and nuclear accumulation. Data mining of a
      genomic database showed that RSV replication induced coordinate changes in Hsp
      family proteins, including the 70, 70-2, 90, 40, and 40-3 isoforms. Because the
      TAR DNA binding protein associates with ND10s, we examined the effect of RSV
      infection on ND10 organization. RSV induced a striking dissolution of ND10
      structures with redistribution of the component promyelocytic leukemia (PML) and
      speckled 100-kDa (Sp100) proteins into the cytoplasm, as well as inducing their
      synthesis. Our findings suggest that cytoplasmic RSV replication induces a
      nuclear heat shock response, causes ND10 disruption, and redistributes PML and
      Sp100 to the cytoplasm. Thus, a high-resolution proteomics approach, combined
      with immunofluorescence localization and coupled with genomic response data,
      yielded unexpected novel insights into compensatory nuclear responses to RSV
      infection.

PMID- 15479788
TI  - Mechanisms of human papillomavirus-induced oncogenesis.

PMID- 15479790
TI  - Impact on genetic networks in human macrophages by a CCR5 strain of human
      immunodeficiency virus type 1.
AB  - Human immunodeficiency virus type 1 (HIV-1) impacts multiple lineages of
      hematopoietic cells, including lymphocytes and macrophages, either by direct
      infection or indirectly by perturbations of cell networks, leading to generalized
      immune deficiency. We designed a study to discover, in primary human macrophages,
      sentinel genetic targets that are impacted during replication over the course of
      7 days by a CCR5-using virus. Expression of mRNA and proteins in virus- or mock
      treated macrophages from multiple donors was evaluated. Hierarchical
      agglomerative cluster analysis grouped into distinct temporal expression patterns
      >900 known human genes that were induced or repressed at least fourfold by virus.
      Expression of more than one-third of the genes was induced rapidly by day 2 of
      infection, while other genes were induced at intermediate (day 4) or late (day 7)
      time points. More than 200 genes were expressed exclusively in either virus- or
      mock-treated macrophage cultures, independent of the donor, providing an
      unequivocal basis to distinguish an effect by virus. HIV-1 altered levels of mRNA
      and/or protein for diverse cellular programs in macrophages, including multiple
      genes that can contribute to a transition in the cell cycle from G(1) to G(2)/M,
      in contrast to expression in mock-treated macrophages of genes that maintain
      G(0)/G(1). Virus treatment activated mediators of cell cycling, including PP2A,
      which is impacted by Vpr, as well as GADD45 and BRCA1, potentially novel targets
      for HIV-1. The results identify interrelated programs conducive to optimal HIV-1
      replication and expression of genes that can contribute to macrophage
      dysfunction.

PMID- 15479791
TI  - The amino terminus of Epstein-Barr Virus (EBV) nuclear antigen 1 contains AT
      hooks that facilitate the replication and partitioning of latent EBV genomes by
      tethering them to cellular chromosomes.
AB  - During latency, Epstein-Barr virus (EBV) is stably maintained as a circular
      plasmid that is replicated once per cell cycle and partitioned at mitosis. Both
      these processes require a single viral protein, EBV nuclear antigen 1 (EBNA1),
      which binds two clusters of cognate binding sites within the latent viral origin,
      oriP. EBNA1 is known to associate with cellular metaphase chromosomes through
      chromosome-binding domains within its amino terminus, an association that we have
      determined to be required not only for the partitioning of oriP plasmids but also
      for their replication. One of the chromosome-binding domains of EBNA1 associates
      with a cellular nucleolar protein, EBP2, and it has been proposed that this
      interaction underlies that ability of EBNA1 to bind metaphase chromosomes. Here
      we demonstrate that EBNA1's chromosome-binding domains are AT hooks, a DNA
      binding motif found in a family of proteins that bind the scaffold-associated
      regions on metaphase chromosomes. Further, we demonstrate that the ability of
      EBNA1 to stably replicate and partition oriP plasmids correlates with its AT hook
      activity and not its association with EBP2. Finally, we examine the contributions
      of EBP2 toward the ability of EBNA1 to associate with metaphase chromosomes in
      human cells, as well as support the replication and partitioning of oriP plasmids
      in human cells. Our results indicate that it is unlikely that EBP2 directly
      mediates these activities of EBNA1 in human cells.

PMID- 15479792
TI  - Direct inoculation of simian immunodeficiency virus from sooty mangabeys in black
      mangabeys (Lophocebus aterrimus): first evidence of AIDS in a heterologous
      African species and different pathologic outcomes of experimental infection.
AB  - A unique opportunity for the study of the role of serial passage and cross
      species transmission was offered by a series of experiments carried out at the
      Tulane National Primate Research Center in 1990. To develop an animal model for
      leprosy, three black mangabeys (BkMs) (Lophocebus aterrimus) were inoculated with
      lepromatous tissue that had been serially passaged in four sooty mangabeys (SMs)
      (Cercocebus atys). All three BkMs became infected with simian immunodeficiency
      virus from SMs (SIVsm) by day 30 postinoculation (p.i.) with lepromatous tissue.
      One (BkMG140) died 2 years p.i. from causes unrelated to SIV, one (BkMG139)
      survived for 10 years, whereas the third (BkMG138) was euthanized with AIDS after
      5 years. Histopathology revealed a high number of giant cells in tissues from
      BkMG138, but no SIV-related lesions were found in the remaining two BkMs. Four
      color immunofluorescence revealed high levels of SIVsm associated with both giant
      cells and T lymphocytes in BkMG138 and no detectable SIV in the remaining two.
      Serum viral load (VL) showed a significant increase (>1 log) during the late
      stage of the disease in BkMG138, as opposed to a continuous decline in VL in the
      remaining two BkMs. With the progression to AIDS, neopterin levels increased in
      BkMG138. This study took on new significance when phylogenetic analysis
      unexpectedly showed that all four serially inoculated SMs were infected with
      different SIVsm lineages prior to the beginning of the experiment. Furthermore,
      the strain infecting the BkMs originated from the last SM in the series.
      Therefore, the virus infecting BkMs has not been serially passaged. In
      conclusion, we present the first compelling evidence that direct cross-species
      transmission of SIV may induce AIDS in heterologous African nonhuman primate
      (NHP) species. The results showed that cross-species-transmitted SIVsm was well
      controlled in two of three BkMs for 2 and 10 years, respectively. Finally, this
      case of AIDS in an African monkey suggests that the dogma of SIV nonpathogenicity
      in African NHP hosts should be reconsidered.

PMID- 15479793
TI  - Redistribution of cellular and herpes simplex virus proteins from the trans-golgi
      network to cell junctions without enveloped capsids.
AB  - Herpes simplex virus (HSV) and other alphaherpesviruses assemble enveloped
      virions in the trans-Golgi network (TGN) or endosomes. Enveloped particles are
      formed when capsids bud into TGN/endosomes and virus particles are subsequently
      ferried to the plasma membrane in TGN-derived vesicles. Little is known about the
      last stages of virus egress from the TGN/endosomes to cell surfaces except that
      the HSV directs transport of nascent virions to specific cell surface domains,
      i.e., epithelial cell junctions. Previously, we showed that HSV glycoprotein
      gE/gI accumulates extensively in the TGN at early times after infection and also
      when expressed without other viral proteins. At late times of infection, gE/gI
      and a cellular membrane protein, TGN46, were redistributed from the TGN to
      epithelial cell junctions. We show here that gE/gI and a second glycoprotein, gB,
      TGN46, and another cellular protein, carboxypeptidase D, all moved to cell
      junctions after infection with an HSV mutant unable to produce cytoplasmic
      capsids. This redistribution did not involve L particles. In contrast to TGN
      membrane proteins, several cellular proteins that normally adhere to the
      cytoplasmic face of TGN, Golgi, and endosomal membranes remained primarily
      dispersed throughout the cytoplasm. Therefore, cellular and viral membrane TGN
      proteins move to cell junctions at late times of HSV infection when the
      production of enveloped particles is blocked. This is consistent with the
      hypothesis that there are late HSV proteins that reorganize or redistribute
      TGN/endosomal compartments to promote virus egress and cell-to-cell spread.

PMID- 15479794
TI  - Influence of acylation sites of influenza B virus hemagglutinin on fusion pore
      formation and dilation.
AB  - The cytoplasmic tail (CT) of hemagglutinin (HA) of influenza B virus (BHA)
      contains at positions 578 and 581 two highly conserved cysteine residues (Cys578
      and Cys581) that are modified with palmitic acid (PA) through a thioester
      linkage. To investigate the role of PA in the fusion activity of BHA, site
      specific mutagenesis was performed with influenza B virus B/Kanagawa/73 HA cDNA.
      All of the HA mutants were expressed on Cos cells by an expression vector. The
      membrane fusion ability of the HA mutants at a low pH was quantitatively examined
      with lipid (octadecyl rhodamine B chloride) and aqueous (calcein) dye transfer
      assays and with the syncytium formation assay. Two deacylation mutants lacking a
      CT or carrying serine residues substituting for Cys578 and Cys581 promoted full
      fusion. However, one of the single-acylation-site mutants, C6, in which Cys581 is
      replaced with serine, promoted hemifusion but not pore formation. In contrast,
      four other single-acylation-site mutants that have a sole cysteine residue in the
      CT at position 575, 577, 579, or 581 promoted full fusion. The impaired pore
      forming ability of C6 was improved by amino acid substitution between residues
      578 and 582 or by deletion of the carboxy-terminal leucine at position 582.
      Syncytium-forming ability, however, was not adequately restored by these
      mutations. These facts indicated that the acylation was not significant in
      membrane fusion by BHA but that pore formation and pore dilation were appreciably
      affected by the particular amino acid sequence of the CT and the existence of a
      single acylation site in CT residue 578.

PMID- 15479795
TI  - Crystal structure of F-93 from Sulfolobus spindle-shaped virus 1, a winged-helix
      DNA binding protein.
AB  - Sulfolobus spindle-shaped viruses (SSVs), or Fuselloviridae, are ubiquitous
      crenarchaeal viruses found in high-temperature acidic hot springs around the
      world (pH </=4.0; temperature of >/=70 degrees C). Because they are relatively
      easy to isolate, they represent the best studied of the crenarchaeal viruses.
      This is particularly true for the type virus, SSV1, which contains a double
      stranded DNA genome of 15.5 kilobases, encoding 34 putative open reading frames.
      Interestingly, the genome shows little sequence similarity to organisms other
      than its SSV homologues. Together, sequence similarity and biochemical analyses
      have suggested functions for only 6 of the 34 open reading frames. Thus, even
      though SSV1 is the best-studied crenarchaeal virus, functions for most (28) of
      its open reading frames remain unknown. We have undertaken biochemical and
      structural studies for the gene product of open reading frame F-93. We find that
      F-93 exists as a homodimer in solution and that a tight dimer is also present in
      the 2.7-A crystal structure. Further, the crystal structure reveals a fold that
      is homologous to the SlyA and MarR subfamilies of winged-helix DNA binding
      proteins. This strongly suggests that F-93 functions as a transcription factor
      that recognizes a (pseudo-)palindromic DNA target sequence.

PMID- 15479796
TI  - Intracellular localization and protein interactions of the gene 1 protein p28
      during mouse hepatitis virus replication.
AB  - Coronaviruses encode the largest replicase polyprotein of any known positive
      strand RNA virus. Replicase protein precursors and mature products are thought to
      mediate the formation and function of viral replication complexes on the surfaces
      of intracellular double-membrane vesicles. However, the functions of only a few
      of these proteins are known. For the coronavirus mouse hepatitis virus (MHV), the
      first proteolytic processing event of the replicase polyprotein liberates an
      amino-terminal 28-kDa product (p28). While previous biochemical studies have
      suggested that p28 is associated with viral replication complexes, the
      intracellular localization and interactions of p28 with other proteins during the
      course of MHV replication have not been defined. We used immunofluorescence
      confocal microscopy to show that p28 localizes to viral replication complexes in
      the cytoplasm during early times postinfection. However, at late times
      postinfection, p28 localizes to sites of M accumulation distinct from the
      replication complex. Furthermore, by yeast two-hybrid and coimmunoprecipitation
      analyses, we demonstrate that p28 specifically binds to p10 and p15, two
      coronavirus replicase proteins of unknown function. Deletion mutagenesis
      experiments determined that the carboxy terminus of p28 is not required for its
      interactions with p10 and p15. These results suggest that p28 may play a part at
      the replication complex by interacting with p10 and p15. Moreover, our findings
      highlight a potential role for p28 at virion assembly sites.

PMID- 15479797
TI  - Evaluation of the functional involvement of human immunodeficiency virus type 1
      integrase in nuclear import of viral cDNA during acute infection.
AB  - Nuclear import of viral cDNA is a critical step for establishing the proviral
      state of human immunodeficiency virus type 1 (HIV-1). The contribution of HIV-1
      integrase (IN) to the nuclear import of viral cDNA is controversial, partly due
      to a lack of identification of its bona fide nuclear localization signal. In this
      study, to address this putative function of HIV-1 IN, the effects of mutations at
      key residues for viral cDNA recognition (PYNP at positions 142 to 145, K156,
      K159, and K160) were evaluated in the context of viral replication. During acute
      infection, some mutations (N144Q, PYNP>KL, and KKK>AAA) severely reduced viral
      gene expression to less than 1% the wild-type (WT) level. None of the mutations
      affected the synthesis of viral cDNA. Meanwhile, the levels of integrated viral
      cDNA produced by N144Q, PYNP>KL, and KKK>AAA mutants were severely reduced to
      less than 1% the WT level. Quantitative PCR analysis of viral cDNA in nuclei and
      fluorescence in situ hybridization analysis showed that these mutations
      significantly reduced the level of viral cDNA accumulation in nuclei. Further
      analysis revealed that IN proteins carrying the N144Q, PYNP>KL, and KKK>AAA
      mutations showed severely reduced binding to viral cDNA but kept their
      karyophilic properties. Taken together, these results indicate that mutations
      that reduced the binding of IN to viral cDNA resulted in severe impairment of
      virus infectivity, most likely by affecting the nuclear import of viral cDNA that
      proceeds integration. These results suggest that HIV-1 IN may be one of the
      critical constituents for the efficient nuclear import of viral cDNA.

PMID- 15479798
TI  - The N- and C-terminal domains of the NS1 protein of influenza B virus can
      independently inhibit IRF-3 and beta interferon promoter activation.
AB  - The NS1 proteins of influenza A and B viruses (A/NS1 and B/NS1 proteins) have
      only approximately 20% amino acid sequence identity. Nevertheless, these proteins
      show several functional similarities, such as their ability to bind to the same
      RNA targets and to inhibit the activation of protein kinase R in vitro. A
      critical function of the A/NS1 protein is the inhibition of synthesis of
      alpha/beta interferon (IFN-alpha/beta) during viral infection. Recently, it was
      also found that the B/NS1 protein inhibits IFN-alpha/beta synthesis in virus
      infected cells. We have now found that the expression of the B/NS1 protein
      complements the growth of an influenza A virus with A/NS1 deleted. Expression of
      the full-length B/NS1 protein (281 amino acids), as well as either its N-terminal
      RNA-binding domain (amino acids 1 to 93) or C-terminal domain (amino acids 94 to
      281), in the absence of any other influenza B virus proteins resulted in the
      inhibition of IRF-3 nuclear translocation and IFN-beta promoter activation. A
      mutational analysis of the truncated B/NS1(1-93) protein showed that RNA-binding
      activity correlated with IFN-beta promoter inhibition. In addition, a recombinant
      influenza B virus with NS1 deleted induces higher levels of IRF-3 activation, as
      determined by its nuclear translocation, and of IFN-alpha/beta synthesis than
      wild-type influenza B virus. Our results support the hypothesis that the NS1
      protein of influenza B virus plays an important role in antagonizing the IRF-3-
      and IFN-induced antiviral host responses to virus infection.

PMID- 15479799
TI  - Infection of vero cells by BK virus is dependent on caveolae.
AB  - Polyomavirus-associated nephropathy occurs in approximately 5% of renal
      transplant recipients and results in loss of graft function in 50 to 70% of these
      patients. The disease is caused by reactivation of the common human polyomavirus
      BK (BKV) in the transplanted kidney. The early events in productive BKV infection
      are unknown. In this report, we focus on elucidating the mechanisms of BKV
      internalization in its target cell. Our data reveal that BKV entry into
      permissive Vero cells is slow, is independent of clathrin-coated-pit assembly, is
      dependent on an intact caveolin-1 scaffolding domain, is sensitive to tyrosine
      kinase inhibition, and requires cholesterol. BKV colocalizes with the caveola
      mediated endocytic marker cholera toxin subunit B but not with the clathrin
      dependent endocytic marker transferrin. In addition, BKV infectious entry is
      sensitive to elevation in intracellular pH. These findings indicate that BKV
      entry into Vero cells occurs by caveola-mediated endocytosis involving a pH
      dependent step.

PMID- 15479800
TI  - Viral evolution and interferon resistance of hepatitis C virus RNA replication in
      a cell culture model.
AB  - Hepatitis C virus (HCV) replicates through an error-prone process that may
      support the evolution of genetic variants resistant to the host cell antiviral
      response and interferon (IFN)-based therapy. We evaluated HCV-IFN interactions
      within a long-term culture system of Huh7 cell lines harboring different variants
      of an HCV type 1b subgenomic RNA replicon that differed at only two sites within
      the NS5A-encoding region. A replicon with a K insertion at HCV codon 2040
      replicated efficiently and exhibited sequence stability in the absence of host
      antiviral pressure. In contrast, a replicon with an L2198S point mutation
      replicated poorly and triggered a cellular response characterized by IFN-beta
      production and low-level IFN-stimulated gene (ISG) expression. When maintained in
      long term-culture, the L2198S RNA evolved into a stable high-passage (HP) variant
      with six additional point mutations throughout the HCV protein-encoding region
      that enhanced viral replication. The HP RNA transduced Huh7 cells with more than
      1,000-fold greater efficiency than its L2198S progenitor or the K2040 sequence.
      Replication of the HP RNA resisted suppression by IFN-alpha treatment and was
      associated with virus-directed reduction in host cell expression of ISG56, an
      antagonist of HCV RNA translation. Accordingly, the HP RNA was retained within
      polyribosome complexes in vivo that were refractory to IFN-induced disassembly.
      These results identify ISG56 as a translational control effector of the host
      response to HCV and provide direct evidence to link this response to viral
      sequence evolution, ISG regulation, and selection of the IFN-resistant viral
      phenotype.

PMID- 15479801
TI  - trans-Packaged West Nile virus-like particles: infectious properties in vitro and
      in infected mosquito vectors.
AB  - A trans-packaging system for West Nile virus (WNV) subgenomic replicon RNAs
      (repRNAs), deleted for the structural coding region, was developed. WNV repRNAs
      were efficiently encapsidated by the WNV C/prM/E structural proteins expressed in
      trans from replication-competent, noncytopathic Sindbis virus-derived RNAs.
      Infectious virus-like particles (VLPs) were produced in titers of up to 10(9)
      infectious units/ml. WNV VLPs established a single round of infection in a
      variety of different cell lines without production of progeny virions. The
      infectious properties of WNV and VLPs were indistinguishable when efficiencies of
      infection of a number of different cell lines and inhibition of infection by
      neutralizing antibodies were determined. To investigate the usefulness of VLPs to
      address biological questions in vivo, Culex pipiens quinquefasciatus mosquitoes
      were orally and parenterally infected with VLPs, and dissected tissues were
      analyzed for WNV antigen expression. Antigen-positive cells in midguts of orally
      infected mosquitoes were detected as early as 2 days postinfection and as late as
      8 days. Intrathoracic inoculation of VLPs into mosquitoes demonstrated a dose
      dependent pattern of infection of secondary tissues and identified fat body,
      salivary glands, tracheal cells, and midgut muscle as susceptible WNV VLP
      infection targets. These results demonstrate that VLPs can serve as a valuable
      tool for the investigation of tissue tropism during the early stages of
      infection, where virus spread and the need for biosafety level 3 containment
      complicate the use of wild-type virus.

PMID- 15479802
TI  - Cells lacking NF-kappaB or in which NF-kappaB is not activated vary with respect
      to ability to sustain herpes simplex virus 1 replication and are not susceptible
      to apoptosis induced by a replication-incompetent mutant virus.
AB  - Earlier we reported that NF-kappaB is activated by protein kinase R (PKR) in
      herpes simplex virus 1-infected cells. Here we report that in PKR(-/-) cells the
      yields of wild-type virus are 10-fold higher than in PKR(+/+) cells. In cells
      lacking NF-kappaB p50 (nfkb1), p65 (relA), or both p50 and p65, the yields of
      virus were reduced 10-fold. Neither wild-type nor mutant cells undergo apoptosis
      following infection with wild-type virus. Whereas PKR(+/+) and NF-kappaB(+/+)
      control cell lines undergo apoptosis induced by the d120 (Deltaalpha4) mutant of
      HSV-1, the mutant PKR(-/-) and NF-kappaB(-/-) cell lines were resistant. The
      evidence suggests that the stress-induced apoptosis resulting from d120 infection
      requires activation of NF-kappaB and that this proapoptotic pathway is blocked in
      cells in which NF-kappaB is not activated or absent. Activation of NF-kappaB in
      the course of viral infection may have dual roles of attempting to curtain viral
      replication by rendering the cell susceptible to apoptosis induced by the virus
      and by inducing the synthesis of proteins that enhance viral replication.

PMID- 15479803
TI  - Differential effects on human immunodeficiency virus type 1 replication by alpha
      defensins with comparable bactericidal activities.
AB  - In addition to their antibacterial activities, certain antimicrobial peptides
      inactivate enveloped viruses, including the human immunodeficiency virus (HIV).
      To determine whether peptide bactericidal activities are predictive of antiviral
      activity, the anti-HIV properties of recombinant human alpha-defensin 5, mouse
      alpha-defensins, cryptdins (Crp) 3 and 4, and rhesus macaque myeloid alpha
      defensins (RMADs) 3 and 4 were determined in vitro. The peptides, purified to
      homogeneity, had equivalent bactericidal activities that were similar to those of
      the native molecules. Nuclear magnetic resonance spectroscopy showed RMAD-4 and
      Crp3 had characteristic alpha-defensin tridisulfide arrays. Of the peptides
      analyzed, only RMAD-4 inhibited HIV infectivity at 150 microg/ml, and Crp3
      unexpectedly increased HIV replication. Quantitative real-time PCRs for minus
      strand strong stop DNA and complete viral cDNA synthesis were used to distinguish
      between preentry and postentry anti-HIV effects by RMAD-4. Viral exposure to RMAD
      4 for 1 h prior to infection reduced HIV minus-strand strong stop DNA and HIV
      cDNA by 4- to 20-fold during the first round of replication, showing that RMAD-4
      exposed virions were not entering cells during the first 24 h. On the other hand,
      when RMAD-4 was added coincident with HIV inoculation, no anti-HIV activity was
      detected. Viral exposure to Crp3 resulted in a threefold increase in both HIV
      minus-strand strong stop DNA and HIV cDNA over the first round of replication.
      Therefore, two alpha-defensins, RMAD-4 and Crp3, inhibit or augment HIV
      replication, respectively, by mechanisms that precede reverse transcription.

PMID- 15479804
TI  - Measles virus phosphoprotein gene products: conformational flexibility of the P/V
      protein amino-terminal domain and C protein infectivity factor function.
AB  - The measles virus (MV) P gene codes for three proteins: P, an essential
      polymerase cofactor, and V and C, which have multiple functions but are not
      strictly required for viral propagation in cultured cells. V shares the amino
      terminal domain with P but has a zinc-binding carboxyl-terminal domain, whereas C
      is translated from an overlapping reading frame. During replication, the P
      protein binds incoming monomeric nucleocapsid (N) proteins with its amino
      terminal domain and positions them for assembly into the nascent
      ribonucleocapsid. The P protein amino-terminal domain is natively unfolded; to
      probe its conformational flexibility, we fused it to the green fluorescent
      protein (GFP), thereby also silencing C protein expression. A recombinant virus
      (MV-GFP/P) expressing hybrid GFP/P and GFP/V proteins in place of standard P and
      V proteins and not expressing the C protein was rescued and produced normal
      ratios of mono-, bi-, and tricistronic RNAs, but its replication was slower than
      that of the parental virus. Thus, the P protein retained nearly intact polymerase
      cofactor function, even with a large domain added to its amino terminus. Having
      noted that titers of cell-associated and especially released MV-GFP/P were
      reduced and knowing that the C protein of the related Sendai virus has particle
      assembly and infectivity factor functions, we produced an MV-GFP/P derivative
      expressing C. Intracellular titers of this virus were almost completely restored,
      and those of released virus were partially restored. Thus, the MV C protein is an
      infectivity factor.

PMID- 15479805
TI  - Reduction of retrovirus-induced immunosuppression by in vivo modulation of T
      cells during acute infection.
AB  - Chronic infection with Friend retrovirus is associated with suppressed antitumor
      immune responses. In the present study we investigated whether modulation of T
      cell responses during acute infection would restore antitumor immunity in
      persistently infected mice. T-cell modulation was done by treatments with DTA-1
      anti- glucocorticoid-induced tumor necrosis factor receptor monoclonal
      antibodies. The DTA-1 monoclonal antibody is nondepleting and delivers
      costimulatory signals that both enhance the activation of effector T cells and
      inhibit suppression by regulatory T cells. DTA-1 therapy produced faster Th1
      immune responses, significant reductions in both acute virus loads and pathology
      and, most importantly, long-term improvement of CD8(+) T-cell-mediated antitumor
      responses.

PMID- 15479806
TI  - Accumulation of cytoplasmic beta-catenin and nuclear glycogen synthase kinase
      3beta in Epstein-Barr virus-infected cells.
AB  - Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with
      cancers in immunocompromised populations. EBV establishes a latent infection and
      immortalizes and transforms B lymphocytes. Several latent proteins have profound
      effects on cellular growth, including activation of NF-kappaB,
      phosphatidylinositol 3'-OH kinase (PI3K) signaling, and notch signaling.
      Activation of PI3K can affect the activity of beta-catenin, the target of the wnt
      signaling pathway. Deregulation of beta-catenin is associated with a number of
      malignancies. To determine if beta-catenin is regulated by EBV infection, EBV
      infected cells were examined for beta-catenin levels and localization. beta
      Catenin was increased in EBV-positive tumor cell lines compared to EBV-negative
      lines, in EBV-infected Burkitt's lymphoma cell lines, and in EBV-transformed
      lymphoblastoid cell lines (LCL). In contrast to wnt signaling, EBV consistently
      induced the accumulation of beta-catenin in the cytoplasm but not the nucleus.
      The beta-catenin regulating kinase, glycogen synthase kinase 3beta (GSK3beta),
      was shown to be phosphorylated and inactivated in EBV-infected lymphocytes.
      Inactivated GSK3beta was localized to the nucleus of EBV-infected LCL. Neither
      the cytoplasmic accumulation of beta-catenin nor the nuclear inactivation of
      GSK3beta was affected by the inhibition of PI3K signaling. These data indicate
      that latent infection with EBV has unique effects on beta-catenin signaling that
      are distinct from activation of wnt and independent of its effects on PI3K.

PMID- 15479807
TI  - Genome-wide analyses of avian sarcoma virus integration sites.
AB  - The chromosomal features that influence retroviral integration site selection are
      not well understood. Here, we report the mapping of 226 avian sarcoma virus (ASV)
      integration sites in the human genome. The results show that the sites are
      distributed over all chromosomes, and no global bias for integration site
      selection was detected. However, RNA polymerase II transcription units (protein
      encoding genes) appear to be favored targets of ASV integration. The integration
      frequency within genes is similar to that previously described for murine
      leukemia virus but distinct from the higher frequency observed with human
      immunodeficiency virus type 1. We found no evidence for preferred ASV integration
      sites over the length of genes and immediate flanking regions. Microarray
      analysis of uninfected HeLa cells revealed that the expression levels of ASV
      target genes were similar to the median level for all genes represented in the
      array. Although expressed genes were targets for integration, we found no
      preference for integration into highly expressed genes. Our results provide a
      more detailed description of the chromosomal features that may influence ASV
      integration and support the idea that distinct, virus-specific mechanisms mediate
      integration site selection. Such differences may be relevant to viral
      pathogenesis and provide utility in retroviral vector design.

PMID- 15479808
TI  - Human cytomegalovirus DNA replication requires transcriptional activation via an
      IE2- and UL84-responsive bidirectional promoter element within oriLyt.
AB  - Amplification of the human cytomegalovirus (HCMV) lytic origin (oriLyt) in human
      fibroblasts is dependent upon six core replication proteins and UL84, IE2, and
      UL36-38. Using a telomerase-immortalized human fibroblast cell line (T-HFs),
      oriLyt-dependent DNA replication no longer required the gene products of UL36-38.
      To determine the role of IE2 in DNA replication in human fibroblasts, we examined
      potential IE2-binding sites within HCMV oriLyt. We now show that a strong
      bidirectional promoter (oriLyt(PM)) (nucleotides 91754 to 92030) is located in
      the previously identified core region of the origin and is required for efficient
      amplification of oriLyt. It was determined that a 14-bp novel DNA motif (oriLyt
      promoter activation element), which was initially identified as a binding element
      for the immediate-early protein IE2, was essential for oriLyt(PM) activity. In
      Vero cells the oriLyt(PM) was constitutively active and strongly repressed by
      IE2, but it was reactivated by UL84. In contrast, transfection of the oriLyt(PM)
      into human fibroblasts resulted in a very low basal level of promoter activity
      that was dramatically up-regulated upon infection with HCMV. Cotransfection
      assays demonstrated that the transfection of UL84 along with IE2 transactivated
      the oriLyt(PM) in human fibroblasts. Further activation was observed upon
      cotransfection of the set of plasmids expressing the entire replication complex.
      Efficient oriLyt amplification in the absence of IE2 in human fibroblasts was
      observed by replacing the oriLyt(PM) with the simian virus 40 early promoter.
      Under these conditions, however, UL84 was still required for amplification of
      oriLyt. These results suggest that the mechanism of initiation of HCMV lytic
      replication in part involves transcriptional activation.

PMID- 15479809
TI  - Evolutionary transition toward defective RNAs that are infectious by
      complementation.
AB  - Passage of foot-and-mouth disease virus (FMDV) in cell culture resulted in the
      generation of defective RNAs that were infectious by complementation. Deletions
      (of nucleotides 417, 999, and 1017) mapped in the L proteinase and capsid protein
      coding regions. Cell killing followed two-hit kinetics, defective genomes were
      encapsidated into separate viral particles, and individual viral plaques
      contained defective genomes with no detectable standard FMDV RNA. Infection in
      the absence of standard FMDV RNA was achieved by cotransfection of susceptible
      cells with transcripts produced in vitro from plasmids encoding the defective
      genomes. These results document the first step of an evolutionary transition
      toward genome segmentation of an unsegmented RNA virus and provide an
      experimental system to compare rates of RNA progeny production and resistance to
      enhanced mutagenesis of a segmented genome versus its unsegmented counterpart.

PMID- 15479810
TI  - Ubiquitination of human T-cell leukemia virus type 1 tax modulates its activity.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) encodes a 40-kDa Tax phosphoprotein.
      Tax is a transcriptional activator which modulates expression of the viral long
      terminal repeat and transcription of many cellular genes. Because Tax is a
      critical HTLV-1 factor which mediates viral transformation of T cells during the
      genesis of adult T-cell leukemia, it is important to understand the processes
      which can activate or inactivate Tax function. Here, we report that
      ubiquitination of Tax is a posttranscriptional mechanism which regulates Tax
      function. We show that ubiquitination does not target Tax for degradation by the
      proteasome. Rather, ubiquitin addition modifies Tax in a proteasome-independent
      manner from an active to a less-active transcriptional form.

PMID- 15479811
TI  - A negative regulatory element (base pairs -204 to -177) of the EICP0 promoter of
      equine herpesvirus 1 abolishes the EICP0 protein's trans-activation of its own
      promoter.
AB  - The early EICP0 protein is a powerful trans-activator that activates all classes
      of equine herpesvirus 1 (EHV-1) promoters but, unexpectedly, trans-activates its
      own promoter very weakly. Transient transfection assays that employed constructs
      harboring deletions within the EICP0 promoter indicated that EICP0 cis-acting
      sequences within bp -224 to -158 relative to the first ATG abolished the EICP0
      protein's trans-activation of its own promoter. When inserted into the promoters
      of other EHV-1 genes, this sequence also downregulated activation of the
      immediate-early IE(-169/+73), early thymidine kinase TK(-215/+97), and late
      glycoprotein K gK(-83/+14) promoters, indicating that the cis-acting sequence (
      224 to -158) downregulated expression of representative promoters of all classes
      of EHV-1 genes and contains a negative regulatory element (NRE). To define the
      cis-acting element(s), three synthetic oligonucleotides (Na [bp -224 to -195], Nb
      [bp -204 to -177], and Nc [bp -185 to -156]) were synthesized and cloned upstream
      of the EICP0(-157/-21) promoter. Of the three synthetic sequences, only the Nb
      oligonucleotide caused the downregulation of the EICP0 promoter. The NRE was
      identified as a 28-bp element to lie at -204 to -177 that encompassed the
      sequence of ([-204]AGATACAGATGTTCGATAAATTGGAACC[-177]). Gel shift assays
      performed with mouse L-M, rabbit RK-13, and human HeLa cell nuclear extracts and
      gamma-(32)P-labeled wild-type and mutant NREs demonstrated that a ubiquitous
      nuclear protein(s) (NRE-binding protein, NREBP) binds specifically to a sequence
      (bp -193 to -183) in the NRE. The NREBP is also present in the nucleus of EHV-1
      infected cells; however, the amount of NREBP in EHV-1-infected L-M cells that
      bound to the Nb oligonucleotide was reduced compared to that in uninfected L-M
      cells. Transient transfection assays showed that deletions or mutations within
      the NREBP-binding site abolished the NRE activity of the EICP0 promoter. These
      results suggested that the NREBP may mediate the NRE activity of the EICP0
      promoter and may function in the coordinate expression of EHV-1 genes.

PMID- 15479812
TI  - Evidence for both lytic replication and tightly regulated human herpesvirus 8
      latency in circulating mononuclear cells, with virus loads frequently below
      common thresholds of detection.
AB  - To address whether human herpesvirus 8 (HHV-8) DNA in peripheral blood
      mononuclear cells (PBMCs) might be the product of latent or lytic infection and
      to shed light on sporadic detection of HHV-8 DNA in individuals seropositive for
      the virus, we studied the frequency of infected cells, total virus load, and
      virus load per infected cell in PBMCs from men coinfected with HHV-8 and human
      immunodeficiency virus (HIV), some of whom had Kaposi's sarcoma. The low
      frequencies of infected cells detected (fewer than one per million cells in some
      individuals) suggest that the prevalence of the virus in circulating leukocytes
      was underestimated in previous studies that employed more conventional sampling
      methods (single, small-volume specimens). Mean virus loads ranged from 3 to 330
      copies per infected PBMC; these numbers can represent much higher loads in
      individual lytically infected cells (>10(3) genomes/cell) in mixtures that
      consist predominantly of latently (relatively few genomes) infected cells. The
      presence in some subjects of high HHV-8 mean genome copy numbers per infected
      cell, together with viral DNA being found in plasma only from subjects with
      positive PBMCs, supports earlier suggestions that the virus can actively
      replicate in PBMCs. In some individuals, mean virus loads were less than 10
      genomes per infected cell, suggesting a tightly controlled purely latent state.
      HHV-8 genome copy numbers are substantially higher in latently infected cells
      derived from primary effusion lymphomas; thus, it appears that HHV-8 is able to
      adopt more than one latency program, perhaps analogous to the several types of
      Epstein-Barr virus latency.

PMID- 15479813
TI  - A novel approach for producing lentiviruses that are limited to a single cycle of
      infection.
AB  - We have devised a novel approach for producing simian immunodeficiency virus
      (SIV) strains and, potentially, human immunodeficiency virus type 1 (HIV-1)
      strains that are limited to a single cycle of infection. Unlike previous
      lentiviral vectors, our single-cycle SIV is capable of expressing eight of the
      nine viral gene products and infected cells release immature virus particles that
      are unable to complete subsequent rounds of infection. Single-cycle SIV (scSIV)
      was produced by using a two-plasmid system specifically designed to minimize the
      possibility of generating replication-competent virus by recombination or
      nucleotide reversion. One plasmid carried a full-length SIV genome with three
      nucleotide substitutions in the gag-pol frameshift site to inactivate Pol
      expression. To ensure inactivation of Pol and to prevent the recovery of wild
      type virus by nucleotide reversion, deletions were also introduced into the viral
      pol gene. In order to provide Gag-Pol in trans, a Gag-Pol-complementing plasmid
      that included a single nucleotide insertion to permanently place gag and pol in
      the same reading frame was constructed. We also mutated the frameshift site of
      this Gag-Pol expression construct so that any recombinants between the two
      plasmids would remain defective for replication. Cotransfection of both plasmids
      into 293T cells resulted in the release of Gag-Pol-complemented virus that was
      capable of one round of infection and one round of viral gene expression but was
      unable to propagate a spreading infection. The infectivity of scSIV was limited
      by the amount of Gag-Pol provided in trans and was dependent on the incorporation
      of a functional integrase. Single-cycle SIV produced by this approach will be
      useful for addressing questions relating to viral dynamics and viral pathogenesis
      and for evaluation as an experimental AIDS vaccine in rhesus macaques.

PMID- 15479814
TI  - Functional analysis of the noncoding regions of the Uukuniemi virus
      (Bunyaviridae) RNA segments.
AB  - The role of the variable portion of the noncoding regions (NCRs) of the three
      Bunyaviridae RNA segments (L, M, S) in transcription, replication, and packaging
      was studied using the recently developed plasmid-driven RNA polymerase I
      minigenome system for Uukuniemi (UUK) virus, genus Phlebovirus (11), as a model.
      Comparison of the different segments showed that all NCRs were sufficient to
      mediate transcription/replication of a minigenome but demonstrated decreased
      promoter strength in the order M > L > S. Chimeric minigenomes with flanking NCRs
      from different genome segments revealed that the number of total base pairs
      within the inverted, partially complementary ends was important for transcription
      and replication. Point mutations increasing the base-pairing potential produced
      increased reporter expression, indicating that complementarity between the 5' and
      3' ends is crucial for promoter activity. The role of the intergenic region (IGR)
      located between the two open reading frames of the ambisense UUK virus S segment
      was analyzed by inserting this sequence element downstream of the reporter genes.
      The presence of the IGR was found to enhance reporter expression, demonstrating
      that efficient transcription termination, regulated by the IGR, is important for
      optimal minigenome mRNA translation. Finally, genome packaging efficacy varied
      for different NCRs and was strongest for L followed by M and S. Strong reporter
      gene activity was still observed after seven consecutive cell culture passages,
      indicating a selective rather than random genome-packaging mechanism. In summary,
      our results demonstrate that the NCRs from all three segments contain the
      necessary signals to initiate transcription and replication as well as packaging.
      Based on promoter strength, M-segment NCRs may be the preferred choice for the
      development of reverse genetics and minigenome rescue systems for bunyaviruses.

PMID- 15479815
TI  - Lv1 inhibition of human immunodeficiency virus type 1 is counteracted by factors
      that stimulate synthesis or nuclear translocation of viral cDNA.
AB  - Human immunodeficiency virus type 1 (HIV-1) cDNA synthesis is inhibited in cells
      from some nonhuman primates by an activity called Lv1. Sensitivity to restriction
      by Lv1 maps to a region of the HIV-1 CA required for interaction with the
      cellular protein cyclophilin A. A similar antiviral activity in mammalian cells,
      Ref1, inhibits reverse transcription of murine leukemia virus (MLV), but only
      with viral strains bearing N-tropic CA. Disruption of the HIV-1 CA-cyclophilin A
      interaction inhibits Lv1 restriction in some cells and, paradoxically, seems to
      render HIV-1 sensitive to Ref1. Lv1 and Ref1 activities are overcome by high
      titer infection and are saturable with nonreplicating, virus-like particles
      encoded by susceptible viruses. Two compounds that disrupt mitochondrial membrane
      potential, As(2)O(3) and m-Cl-CCP, reduce Ref1 activity. Here we show that these
      drugs, as well as a third compound with similar effects on mitochondria, PK11195,
      attenuate Lv1 activity in rhesus macaque and African green monkey cells. Effects
      of PK11195 and virus-like particles on HIV-1 infectivity in these cells were
      largely redundant, each associated with increased HIV-1 cDNA. Comparison of
      acutely infected macaque and human cells suggested that, in addition to effects
      on cDNA synthesis, Lv1 inhibits the accumulation of nuclear forms of HIV-1 cDNA.
      Disruption of the HIV-1 CA-cyclophilin A interaction caused a minimal increase in
      total viral cDNA but increased the proportion of viral cDNA in the nucleus.
      Consistent with a model in which Lv1 inhibits both synthesis and nuclear
      translocation of HIV-1 cDNA, complete suppression of macaque or African green
      monkey Lv1 was achieved by the additive effect of factors that stimulate both
      processes.

PMID- 15479816
TI  - Translation of duck hepatitis B virus reverse transcriptase by ribosomal
      shunting.
AB  - The duck hepatitis B virus (DHBV) polymerase (P) is translated by de novo
      initiation from a downstream open reading frame (ORF) that partially overlaps the
      core (C) ORF on the bicistronic pregenomic RNA (pgRNA). The DHBV P AUG is in a
      poor context for translational initiation and is preceded by 14 AUGs that could
      intercept scanning ribosomes, yet P translation is unanticipatedly rapid.
      Therefore, we assessed C and P translation in the context of the pgRNA. Mutating
      the upstream C ORF revealed that P translation was inversely related to C
      translation, primarily due to occlusion of P translation by ribosomes translating
      C. Translation of the pgRNA was found to be cap dependent, because inserting a
      stem-loop (BamHI-SL) that blocked >90% of scanning ribosomes at the 5' end of the
      pgRNA greatly inhibited C and P synthesis. Neither mutating AUGs between the C
      and P start sites in contexts similar to that of the P AUG nor blocking ribosomal
      scanning by inserting the BamHI-SL between the C and P start codons greatly
      altered P translation, indicating that most ribosomes that translate P do not
      scan through these sequences. Finally, optimizing the P AUG context did not
      increase P translation. Therefore, the majority of the ribosomes that translate P
      are shunted from a donor region near the 5' end of the pgRNA to an acceptor site
      at or near the P AUG, and the shunt acceptor sequences may augment initiation at
      the P AUG.

PMID- 15479817
TI  - Between-host evolution of cytotoxic T-lymphocyte epitopes in human
      immunodeficiency virus type 1: an approach based on phylogenetically independent
      comparisons.
AB  - In human immunodeficiency virus type 1 (HIV-1), mutations that escape from
      cytotoxic T-lymphocyte (CTL) recognition have been documented, and sequence
      analyses have provided indirect support for the hypothesis that natural selection
      has favored CTL escape mutants within an infected host. In spite of such evidence
      for within-host selection by CTL, it has been more difficult to determine how
      natural selection by host CTL has influenced long-term evolution of HIV-1. We
      used statistical analysis of published HIV-1 genomic sequences to examine the
      role of natural selection in between-host evolution of CTL epitopes. Based on a
      phylogenetic analysis, we identified 21 pairs of closely related genomes isolated
      from different hosts and examined the pattern of nucleotide substitution in
      genomic regions encoding well-characterized CTL epitopes. The results revealed
      that certain CTL epitopes have been subject to repeated positive selection across
      the population, while others are generally conserved. Furthermore, evidence of
      positive selection was associated with divergence from the canonical epitope
      sequence and with an enhanced frequency of convergent amino acid sequence changes
      in CTL epitopes. The results support the hypothesis that CTL-driven selection has
      been a major factor in the long-term evolution of HIV-1.

PMID- 15479818
TI  - Membrane binding properties and terminal residues of the mature hepatitis C virus
      capsid protein in insect cells.
AB  - The immature core protein (p23, residues 1 to 191) of hepatitis C virus undergoes
      posttranslational modifications including intramembranous proteolysis within its
      C-terminal signal sequence by signal peptide peptidase to generate the mature
      form (p21). In this study, we analyzed the cleavage site and other amino acid
      modifications that occur on the core protein. To produce the posttranslationally
      modified core protein, we used a baculovirus-insect cell expression model system.
      As previously reported, p23 is processed to form p21 in insect as well as in
      mammalian cells. p21 was found to be associated with the cytoplasmic membrane,
      and its significant portion behaved as an integral membrane protein. The protein
      was purified from the membrane by a simple and unique procedure on the basis of
      its membrane-binding properties and solubility in detergents. Matrix-assisted
      laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)
      analysis of purified p21 showed that the average molecular mass (m/z 19,307) of
      its single-charged ion differs by m/z 1,457 from that calculated for p23. To
      determine the posttranslational modifications, tryptic p21 peptides were analyzed
      by MALDI-TOF MS. We found three peptides that did not match the theoretically
      derived peptides of p23. Analysis of these peptides by MALDI-TOF tandem MS
      revealed that they correspond to N-terminal peptides (residues 2 to 9 and 2 to
      10) starting with alpha-N-acetylserine and C-terminal peptide (residues 150 to
      177) ending with phenylalanine. These results suggest that the mature core
      protein (molecular mass of 19,306 Da) includes residues 2 to 177 and that its N
      terminus is blocked with an acetyl group.

PMID- 15479819
TI  - The C-mer gene is induced by Epstein-Barr virus immediate-early protein BRLF1.
AB  - BRLF1 (R) is one of two Epstein-Barr virus (EBV) immediate-early proteins that
      mediate the switch from the latent to the lytic form of viral replication. In
      this report, we show that R induces expression of the cellular C-mer gene in a
      variety of cell lines. C-mer expression was detected in lymphoblastoid cells
      immortalized with wild-type EBV but not in lymphoblastoid cells immortalized with
      an EBV that had BRLF1 deleted. Oral hairy leukoplakia tongue tissue, which
      contains the lytic form of EBV replication, also has enhanced C-mer expression. C
      mer is a receptor tyrosine kinase activated by the ligand Gas6. C-mer is required
      for phagocytosis of apoptotic debris by monocytes/macrophages and retinal pigment
      epithelial cells and is capable of producing an antiapoptotic signal. Modulation
      of the C-mer signal transduction cascade by a variety of different approaches did
      not alter the ability of R to induce lytic EBV gene transcription. Therefore, C
      mer activation may be important for some other aspect of lytic EBV infection.

PMID- 15479820
TI  - Effects on rotavirus cell binding and infection of monomeric and polymeric
      peptides containing alpha2beta1 and alphaxbeta2 integrin ligand sequences.
AB  - Integrin-using rotaviruses bind MA104 cell surface alpha2beta1 integrin via the
      Asp-Gly-Glu (DGE) sequence in virus spike protein VP4 and interact with
      alphaxbeta2 integrin during cell entry through outer capsid protein VP7.
      Infection is inhibited by the alpha2beta1 ligand Asp-Gly-Glu-Ala (DGEA) and the
      alphaxbeta2 ligand Gly-Pro-Arg-Pro (GPRP), and virus-alpha2beta1 binding is
      increased by alpha2beta1 activation. In this study, we analyzed the effects of
      monomers and polymers containing DGEA-, GPRP-, and DGEA-related peptides on
      rotavirus binding and infection in intestinal (Caco-2) and kidney (MA104) cells
      and virus binding to recombinant alpha2beta1. Blockade of rotavirus-cell binding
      and infection by peptides and anti-alpha2 antibody showed that Caco-2 cell entry
      is dependent on virus binding to alpha2beta1 and interaction with alphaxbeta2. At
      up to 0.5 mM, monomeric DGEA and DGAA inhibited binding to alpha2beta1 and
      infection. At higher concentrations, DGEA and DGAA showed a reduced ability to
      inhibit virus-cell binding and infection that depended on virus binding to
      alpha2beta1 but occurred without alteration in cell surface expression of alpha2,
      beta2, or alphavbeta3 integrin. This loss of DGEA activity was abolished by
      genistein treatment and so was dependent on tyrosine kinase signaling. It is
      proposed that this signaling activated existing cell surface alpha2beta1 to
      increase virus-cell attachment and entry. Polymeric peptides containing DGEA and
      GPRP or GPRP only were inhibitory to SA11 infection at approximately 10-fold
      lower concentrations than peptide monomers. As polymerization can improve peptide
      inhibition of virus-receptor interactions, this approach could be useful in the
      development of inhibitors of receptor recognition by other viruses.

PMID- 15479821
TI  - Inhibition of Epstein-Barr virus (EBV) reactivation by short interfering RNAs
      targeting p38 mitogen-activated protein kinase or c-myc in EBV-positive
      epithelial cells.
AB  - Latent Epstein-Barr virus (EBV) is reactivated by 12-O-tetradecanoylphorbol-13
      acetate (TPA) in EBV-infected cells. In this study, we found that TPA up
      regulated phosphorylation of p38, a mitogen-activated protein kinase, and
      activated c-myc mRNA in EBV-positive epithelial GT38 cells. The EBV immediate
      early gene BZLF1 mRNA and its product ZEBRA protein were induced following TPA
      treatment. Protein kinase C inhibitors, 1-(5-isoquinolinesulphonyl)-2, 5
      dimethylpiperazine (H7) and staurosporine, inhibited the induction of p38
      phosphorylation and the activation of c-Myc by TPA. The p38 inhibitor SB203580
      blocked both p38 phosphorylation and ZEBRA expression by TPA. Pretreatment of
      GT38 cells with the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine
      inhibited p38 phosphorylation and c-Myc activation by TPA, suggesting that NO may
      inhibit EBV reactivation via both p38 and c-Myc. By using short interfering RNA
      (siRNA) targeting either p38 or c-myc, we found that p38 or c-myc siRNA
      specifically inhibited expression of the respective gene and also suppressed the
      induction of ZEBRA and EBV early antigen. The interferon (IFN)-responsive gene
      expression tests ruled out the possibility that the antiviral effect of siRNA is
      dependent on IFN. Our present study demonstrates for the first time that either
      p38 or c-myc siRNA can efficiently inhibit TPA-induced EBV reactivation in GT38
      cells, indicating that p38- and/or c-myc-associated signaling pathways may play
      critical roles in the disruption of EBV latency by TPA.

PMID- 15479822
TI  - Coevolution of RANTES sensitivity and mode of CCR5 receptor use by human
      immunodeficiency virus type 1 of the R5 phenotype.
AB  - The evolution of human immunodeficiency virus type 1 (HIV-1) coreceptor use has
      been described as the acquisition of CXCR4 use linked to accelerated disease
      progression. However, CXCR4-using virus can be isolated only from approximately
      one-half of individuals with progressive HIV-1 disease. The other half continue
      to yield only CCR5-using viruses (R5 phenotype) throughout the course of disease.
      In the present work, the use of receptor chimeras between CCR5 and CXCR4 allowed
      us to study the evolution of HIV-1 with the R5 phenotype, which was not revealed
      by studies of wild-type coreceptor use. All together, 246 isolates (173 with the
      R5 phenotype) from 31 individuals were tested for their ability to infect cells
      through receptor chimeras. R5(narrow) virus was able to use only wild-type CCR5,
      whereas R5(broad(1)) to R5(broad(3)) viruses were able to use one to three
      chimeric receptors, respectively. Broad use of chimeric receptors was interpreted
      as an increased flexibility in the mode of receptor use. R5(broad) isolates
      showed higher infectivity in cells expressing wild-type CCR5 than R5(narrow)
      isolates. Also, the increased flexibility of R5(broad) isolates was concomitant
      with a lower sensitivity to inhibition by the CC chemokine RANTES. Our results
      indicate a close relationship between HIV-1 phenotypic changes and the pathogenic
      process, since the mode and efficiency of CCR5 use as well as the decrease in the
      RANTES sensitivities of isolated viruses are significantly correlated with CD4(+)
      T-cell decline in a patient. One possible explanation is that ligand competition
      at the CCR5 receptor or changed CCR5 availability may shape the outcome of HIV-1
      infection.

PMID- 15479823
TI  - Influence of gag on human immunodeficiency virus type 1 species-specific tropism.
AB  - The narrow host range of human immunodeficiency virus type 1 (HIV-1) is due in
      part to dominant acting restriction factors in humans (Ref1) and monkeys (Lv1).
      Here we show that gag encodes determinants of species-specific lentiviral
      infection, related in part to such restriction factors. Interaction between
      capsid and host cyclophilin A (CypA) protects HIV-1 from restriction in human
      cells but is essential for maximal restriction in simian cells. We show that
      sequence variation between HIV-1 isolates leads to variation in sensitivity to
      restriction factors in human and simian cells. We present further evidence for
      the importance of target cell CypA over CypA packaged in virions, specifically in
      the context of gp160 pseudotyped HIV-1 vectors. We also show that sensitivity to
      restriction is controlled by an H87Q mutation in the capsid, implicated in the
      immune control of HIV-1, possibly linking immune and innate control of HIV-1
      infection.

PMID- 15479824
TI  - Stable ubiquitination of human T-cell leukemia virus type 1 tax is required for
      proteasome binding.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is the retrovirus responsible for
      adult T-cell leukemia and HTLV-1-associated myelopathy. Adult T-cell leukemia
      development is mainly due to the ability of the viral oncoprotein Tax to promote
      T-cell proliferation, whereas the appearance of HTLV-1-associated myelopathy
      involves the antigenic properties of Tax. Understanding the events regulating the
      intracellular level of Tax is therefore an important issue. How Tax is degraded
      has not been determined, but it is known that Tax binds to proteasomes, the major
      sites for degradation of intracellular proteins, generally tagged through
      polyubiquitin conjugation. In this study, we investigated the relationship
      between Tax, ubiquitin, and proteasomes. We report that mono- and
      polyubiquitinated Tax proteins can be recovered from both transfected 293T cells
      and T lymphocytes. We also show that lysine residues located in the carboxy
      terminal domain of Tax are the principal targets of this process. Remarkably, we
      further demonstrate that mutation of lysine residues in the C-terminal part of
      Tax, which massively reduces Tax ubiquitination, impairs proteasome binding, and
      conversely, that a Tax mutant that binds poorly to this particle (M22) is faintly
      ubiquitinated, suggesting that Tax ubiquitination is required for association
      with cellular proteasomes. Finally, we document that comparable amounts of
      ubiquitinated species were found whether proteasome activities were inhibited or
      not, providing evidence that they are not directly addressed to proteasomes for
      degradation. These findings indicate that although it is ubiquitinated and binds
      to proteasomes, Tax is not massively degraded via the ubiquitin-proteasome
      pathway and therefore reveal that Tax conjugation to ubiquitin mediates a
      nonproteolytic function.

PMID- 15479825
TI  - The varicella-zoster virus open reading frame 63 latency-associated protein is
      critical for establishment of latency.
AB  - Varicella-zoster virus (VZV) expresses at least six viral transcripts during
      latency. One of these transcripts, derived from open reading frame 63 (ORF63), is
      one of the most abundant viral RNAs expressed during latency. The VZV ORF63
      protein has been detected in human and experimentally infected rodent ganglia by
      several laboratories. We have deleted >90% of both copies of the ORF63 gene from
      the VZV genome. Animals inoculated with the ORF63 mutant virus had lower mean
      copy numbers of latent VZV genomes in the dorsal root ganglia 5 to 6 weeks after
      infection than animals inoculated with parental or rescued virus, and the
      frequency of latently infected animals was significantly lower in animals
      infected with the ORF63 mutant virus than in animals inoculated with parental or
      rescued virus. In contrast, the frequency of animals latently infected with viral
      mutants in other genes that are equally or more impaired for replication in
      vitro, compared with the ORF63 mutant, is similar to that of animals latently
      infected with parental VZV. Examination of dorsal root ganglia 3 days after
      infection showed high levels of VZV DNA in animals infected with either ORF63
      mutant or parental virus; however, by days 6 and 10 after infection, the level of
      viral DNA in animals infected with the ORF63 mutant was significantly lower than
      that in animals infected with parental virus. Thus, ORF63 is not required for VZV
      to enter ganglia but is the first VZV gene shown to be critical for establishment
      of latency. Since the present vaccine can reactivate and cause shingles, a VZV
      vaccine based on the ORF63 mutant virus might be safer.

PMID- 15479826
TI  - Amino-terminal region of the human immunodeficiency virus type 1 nucleocapsid is
      required for human APOBEC3G packaging.
AB  - APOBEC3G exerts its antiviral activity by targeting to retroviral particles and
      inducing viral DNA hypermutations in the absence of Vif. However, the mechanism
      by which APOBEC3G is packaged into virions remains unclear. We now report that
      viral genomic RNA enhances but is not essential for human APOBEC3G packaging into
      human immunodeficiency virus type 1 (HIV-1) virions. Packaging of APOBEC3G was
      also detected in HIV-1 Gag virus-like particles (VLP) that lacked all the viral
      genomic RNA packaging signals. Human APOBEC3G could be packaged efficiently into
      a divergent subtype HIV-1, as well as simian immunodeficiency virus, strain mac,
      and murine leukemia virus Gag VLP. Cosedimentation of human APOBEC3G and
      intracellular Gag complexes was detected by equilibrium density and velocity
      sucrose gradient analysis. Interaction between human APOBEC3G and HIV-1 Gag was
      also detected by coimmunoprecipitation experiments. This interaction did not
      require p6, p1, or the C-terminal region of NCp7. However, the N-terminal region,
      especially the first 11 amino acids, of HIV-1 NCp7 was critical for HIV-1 Gag and
      APOBEC3G interaction and virion packaging. The linker region flanked by the two
      active sites of human APOBEC3G was also important for efficient packaging into
      HIV-1 Gag VLP. Association of human APOBEC3G with RNA-containing intracellular
      complexes was observed. These results suggest that the N-terminal region of HIV-1
      NC, which is critical for binding to RNA and mediating Gag-Gag oligomerization,
      plays an important role in APOBEC3G binding and virion packaging.

PMID- 15479827
TI  - The putative zinc finger of the human cytomegalovirus IE2 86-kilodalton protein
      is dispensable for DNA binding and autorepression, thereby demarcating a concise
      core domain in the C terminus of the protein.
AB  - The IE2 86-kDa gene product is an essential regulatory protein of human
      cytomegalovirus (HCMV) with several functions, including transactivation,
      negative autoregulation, and cell cycle regulation. In order to understand the
      physiological significance of each of the IE2 functions, discriminating mutants
      of IE2 are required that can be tested in a viral background. However, no such
      mutants of IE2 are available, possibly reflecting structural peculiarities of the
      large and ill-defined C-terminal domain of IE2. Here, we revisited the C-terminal
      domain by analyzing IE2 mutants for transactivation, DNA binding, autoregulation,
      and cell cycle regulation in parallel. We found it to contain an unexpectedly
      concise core domain (amino acids 450 to 544) that is defined by its absolute
      sensitivity to any kind of mutation. In contrast, the region adjacent to the core
      (amino acids 290 to 449) generally tolerates mutations much better. Although it
      contributes more specific sequence information to distinct IE2 activities, none
      of the mutations analyzed abolished any particular function. The core is
      demarcated from the adjacent region by the putative zinc finger region (amino
      acids 428 to 452). Surprisingly, the deletion of the putative zinc finger region
      from IE2 revealed that this region is entirely dispensable for any of the IE2
      functions tested here in transfection assays. Our work supports the view that the
      100 amino acids of the core domain hold the key to most functions of IE2. A
      systematic, high-density mutational analysis of this region may identify
      informative mutants discriminating between various IE2 functions that can then be
      tested in a viral background.

PMID- 15479828
TI  - Calcium-dependent calpain proteases are implicated in processing of the hepatitis
      C virus NS5A protein.
AB  - The nonstructural 5A (NS5A) protein of the hepatitis C virus (HCV) is a
      multifunctional phosphoprotein that is implicated in viral replication and HCV
      mediated pathogenesis. We report here that the NS5A protein from the HCV genotype
      1a is processed into shorter distinct forms when expressed in mammalian cells
      (Vero, HepG2, HuH-7, and WRL68) infected with an NS5A-expressing HSV-1-based
      amplicon vector or when transiently transfected with NS5A-expressing plasmids in
      the absence of exogenous apoptotic stimuli. Inhibitor studies combined with cell
      free cleavage assays suggest that calcium-dependent calpain proteases, in
      addition to caspase-like proteases, are involved in NS5A processing.
      Interestingly, His-tagging experiments indicated that all the detectable NS5A
      cleaved products are N-terminal forms of the protein. Additionally,
      immunofluorescence studies showed that, despite proteolytic cleavage, the NS5A
      protein exhibits a cytoplasm-perinuclear localization similar to that of the full
      length protein. Thus, our results are consistent with recent data that
      demonstrated that NS5A is capable of perturbing intracellular calcium homeostasis
      and suggest that NS5A is both an inducer and a substrate of the calcium-dependent
      calpain protease(s). This may imply that cleavage of NS5A by calpain(s) could
      play a role in the modulation of NS5A function.

PMID- 15479829
TI  - Essential function of the pseudorabies virus UL36 gene product is independent of
      its interaction with the UL37 protein.
AB  - The large tegument protein encoded by the UL36 gene of pseudorabies virus (PrV)
      physically interacts with the product of the adjacent UL37 gene (B. G. Klupp, W.
      Fuchs, H. Granzow, R. Nixdorf, and T. C. Mettenleiter, J. Virol. 76:3065-3071,
      2002). To analyze UL36 function, two PrV recombinants were generated by
      mutagenesis of an infectious PrV full-length clone in Escherichia coli: PrV
      DeltaUL36F exhibited a deletion of virtually the complete UL36 coding region,
      whereas PrV-UL36BSF contained two in-frame deletions of 238 codons spanning the
      predicted UL37 binding domain. Coimmunoprecipitation experiments confirmed that
      the mutated gene product of PrV-UL36BSF did not interact with the UL37 protein.
      Like the previously described PrV-DeltaUL37 (B. G. Klupp, H. Granzow, and T. C.
      Mettenleiter, J. Virol. 75:8927-8936, 2001) but in contrast to PrV-DeltaUL36F,
      PrV-UL36BSF was able to replicate in rabbit kidney (RK13) cells, although maximum
      virus titers were reduced ca. 50-fold and plaque diameters were reduced by ca.
      45% compared to wild-type PrV. PrV-DeltaUL36F was able to productively replicate
      after repair of the deleted gene or in a trans-complementing cell line. Electron
      microscopy of infected RK13 cells revealed that PrV-UL36BSF and phenotypically
      complemented PrV-DeltaUL36F were capable of nucleocapsid formation and egress
      from the nucleus by primary envelopment and deenvelopment at the nuclear
      membrane. However, reenvelopment of nucleocapsids in the cytoplasm was blocked.
      Only virus-like particles without capsids were released efficiently from cells.
      Interestingly, cytoplasmic nucleocapsids of PrV-UL36BSF but not of PrV-DeltaUL36F
      were found in large ordered structures similar to those which had previously been
      observed with PrV-DeltaUL37. In summary, our results demonstrate that the
      interaction between the UL36 and UL37 proteins is important but not strictly
      essential for the formation of secondary enveloped, infectious PrV particles.
      Furthermore, UL36 possesses an essential function during virus replication which
      is independent of its ability to bind the UL37 protein.

PMID- 15479830
TI  - PCNA interacts with Indian mung bean yellow mosaic virus rep and downregulates
      Rep activity.
AB  - Proliferative cell nuclear antigen (PCNA), a conserved plant protein as well as
      an important replication factor, is induced in response to geminivirus infection
      in the resting cells of the phloem tissues. The biochemical role of PCNA in
      rolling circle replication (RCR) of geminivirus DNA has not been explored in
      detail. The initiation of RCR of the bipartite genome of a geminivirus, Indian
      mung bean yellow mosaic virus (IMYMV), is mainly controlled by viral protein Rep
      (or AL1 or AC1). The role of host PCNA in RCR of IMYMV was revealed by studying
      the physical and functional interactions between recombinant PCNA and recombinant
      IMYMV Rep. Pea nuclear PCNA as well as recombinant pea PCNA showed binding to
      recombinant Rep in experiments involving both affinity chromatography and yeast
      two-hybrid approaches. The contacting amino acid residues of PCNA seemed to be
      present throughout a wide region of the trimeric protein, while those of Rep
      appeared to be localized only in the middle part of the protein. The site
      specific nicking-closing activity and the ATPase function of IMYMV Rep were
      impaired by PCNA. These observations lead to interesting speculations about the
      control of viral RCR and dynamic profiles of protein-protein interactions at the
      RCR origin of the geminiviruses.

PMID- 15479831
TI  - Endocytic host cell machinery plays a dominant role in intracellular trafficking
      of incoming human immunodeficiency virus type 1 in human placental trophoblasts.
AB  - Vertical transmission of human immunodeficiency virus type 1 (HIV-1) is the
      primary cause of infection by this retrovirus in infants. In this study, we
      report for the first time that there is a correlation between endocytic uptake of
      HIV-1 and virus gene expression in polarized trophoblasts. To shed light on the
      relationship between endocytosis and the fate of HIV-1 in polarized trophoblasts,
      the step-by-step movements of HIV-1 within the endocytic compartments were
      tracked by confocal imaging. Incoming virions were initially located in early
      endosomes. As time progressed, virions accumulated in late endosomes. HIV-1 was
      also found in apical recycling endosomes and at the basolateral pole. Experiments
      performed with indicator cells revealed that HIV-1 is recycled and transcytosed.
      These data indicate that the intracellular trafficking of HIV-1 upon entry into
      polarized human trophoblasts is a complex process which requires the active
      participation of the endocytic host cell machinery.

PMID- 15479832
TI  - Interaction between the cytoplasmic domain of ICAM-1 and Pr55Gag leads to
      acquisition of host ICAM-1 by human immunodeficiency virus type 1.
AB  - We have examined the molecular basis for the selective incorporation of the
      adhesion molecule ICAM-1 within human immunodeficiency virus type 1 (HIV-1). The
      process of ICAM-1 incorporation was investigated by using different ICAM-1
      constructs in combination with virus capture and immunoprecipitation studies,
      Western blot and confocal microscopy analyses, and infectivity assays.
      Experiments conducted with viruses bearing a truncated version of ICAM-1 revealed
      that the cytoplasmic domain of ICAM-1 governs insertion of this adhesion molecule
      into HIV-1. Further experiments suggested that there is an association between
      ICAM-1 and the virus-encoded Pr55(Gag) polyprotein. This study represents the
      first demonstration that structural Gag polyproteins play a key role in the
      uptake of a host-derived cell surface by the virus entity. Taken together, our
      results indicate that interactions between viral and cellular proteins are
      responsible for the selective uptake of host ICAM-1 by HIV-1. This observation
      describes a new strategy by which HIV-1 can modulate its replicative cycle,
      considering that insertion of ICAM-1 within nascent virions has been shown to
      increase virus infectivity.

PMID- 15479834
TI  - Early stage of establishment of persistent Sendai virus infection: unstable
      dynamic phase and then selection of viruses which are tightly cell associated,
      temperature sensitive, and capable of establishing persistent infection.
AB  - We obtained 157 cloned cell lines persistently infected with Sendai virus; these
      cell lines were generated independently of each other. Infectious viruses could
      be isolated from 123 of these cloned cell lines by inoculation of culture fluids
      or infected cells into embryonated eggs. The majority of the viruses carried by
      cells persistently infected with viruses showed high cytotoxicity and did not
      have the ability to establish persistent infection. The association of carried
      virus with cells became stronger and virus isolation correspondingly became more
      difficult as cells persistently infected with virus were subcultured. Viruses
      derived from virus-infected cells eventually acquired the ability to establish
      persistent infection, although the ways in which the viruses acquired this
      ability varied. The viruses also acquired temperature sensitivity as persistently
      infected cells were subcultured. First, the hemagglutinin-neuraminidase and M
      proteins acquired temperature sensitivity, and then the polymerase(s) did so. The
      M proteins were localized in the nuclei of cells infected with cloned viruses
      that had the ability to establish persistent infection. Cells infected with
      viruses capable of establishing persistent infection showed no or slight staining
      by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling.
      Specific amino acid substitutions accumulated in the M protein and the L protein
      as virus-infected cells were subcultured. This study shows that there is an
      unstable dynamic phase at an early stage of the establishment of persistent
      Sendai virus infection (steady state), and then viruses capable of establishing
      persistent infection are selected.

PMID- 15479833
TI  - Activation of transcription factor Nrf-2 and its downstream targets in response
      to moloney murine leukemia virus ts1-induced thiol depletion and oxidative stress
      in astrocytes.
AB  - The neuroimmunodegenerative syndrome that develops in mice infected with ts1, a
      mutant of Moloney murine leukemia virus, resembles human AIDS. Both ts1 and human
      immunodeficiency virus type 1 infect astrocytes, microglia, and oligodendrocytes
      but do not infect neurons. Oxidative stress has been implicated in the
      neuropathology of AIDS dementia and other neurodegenerative diseases. We report
      here that ts1 infection of astrocytes (both transformed C1 cells and primary
      cultures) also induces thiol (i.e., glutathione and cysteine) depletion and
      reactive oxygen species (ROS) accumulation, events occurring in parallel with
      viral envelope precursor gPr80(env) accumulation and upregulated expression of
      endoplasmic reticulum chaperones GRP78 and GRP94. Furthermore, ts1-infected
      astrocytes mobilize their thiol redox defenses by upregulating levels of the Nrf
      2 transcription factor, as well its targets, the xCT cystine/glutamate
      antiporter, gamma-glutamylcysteine ligase, and glutathione peroxidase. Depleting
      intracellular thiols by treating uninfected astrocytes with buthionine
      sulfoximine (BSO), a glutathione synthesis inhibitor, or by culturing in cystine
      deficient medium, also induces ROS accumulation, activates Nrf-2, and upregulates
      Nrf-2 target gene expression in these astrocytes. Overexpression of Nrf-2 in
      astrocytes specifically increases expression of the above thiol synthesis-related
      proteins. Further treatment with BSO or N-acetylcysteine in transfected cells
      modulates this expression. Thiol depletion also accelerates cell death, while
      thiol supplementation promotes survival of ts1-infected cells. Together, our
      results indicate that ts1 infection of astrocytes, along with ts1-induced
      gPr80(env) accumulation, endoplasmic reticulum stress, thiol depletion, and
      oxidative stress, accelerates cell death; in response to the thiol depletion and
      oxidative stress, astrocytes activate their Nrf-2-mediated thiol antioxidant
      defenses, promoting cell survival.

PMID- 15479835
TI  - Cell surface delivery of the measles virus nucleoprotein: a viral strategy to
      induce immunosuppression.
AB  - Although only a few blood cells are infected during measles, this infectious
      disease is followed by acute immunosuppression, associated with high infant
      mortality. Measles virus nucleoprotein has been suggested to contribute to virus
      induced inhibition of the immune response. However, it has been difficult to
      understand how this cytosolic viral protein could leave an infected cell and then
      perturb the immune response. Here we demonstrate that intracellularly synthesized
      nucleoprotein enters the late endocytic compartment, where it recruits its
      cellular ligand, the Fcgamma receptor. Nucleoprotein is then expressed at the
      surfaces of infected leukocytes associated with the Fcgamma receptor and is
      secreted into the extracellular compartment, allowing its interaction with
      uninfected cells. Finally, cell-derived nucleoprotein inhibits the secretion of
      interleukin-12 and the generation of the inflammatory reaction, both shown to be
      impaired during measles. These results reveal nucleoprotein egress from infected
      cells as a novel strategy in measles-induced immunosuppression.

PMID- 15479836
TI  - Identification of a negative regulatory element in the Epstein-Barr virus Zta
      transactivation domain that is regulated by the cell cycle control factors c-Myc
      and E2F1.
AB  - Reactivation in Epstein-Barr virus (EBV) is closely associated with a G(0)/G(1)
      cell cycle arrest which can be induced either by lytic cycle-inducing agents or
      by the immediate-early gene product Zta. Accumulating evidence shows that in
      epithelial cells, downregulation of the proto-oncogene, c-myc, plays an important
      role in lytic cycle-associated cell growth arrest. Here, we provide evidence that
      c-Myc provides a gatekeeper function to ensure that certain cell cycle inhibitory
      events have been capitulated prior to full progression into the lytic cycle.
      Specifically, we show that reconstitution of c-Myc expression during the lytic
      cycle to levels observed in cycling uninduced cells inhibits the transactivation
      function of Zta. Nuclear localization studies show that c-Myc does not grossly
      alter the nuclear localization of Zta or its association with the insoluble
      nuclear fraction. Enforced expression of another transcription factor that
      promotes cell cycle progression, E2F1, also inhibits Zta transactivation.
      Analysis of c-Myc- and E2F1-mediated inhibition of a panel of Zta mutants shows
      parallel genetics and inhibition maps to a small bipartite sequence located
      between amino acids 29 and 53 of Zta, containing homology to the proline-rich
      domain of the tumor suppressor protein p53. Mutation of a conserved tryptophan
      residue located at amino acid 49 of Zta largely prevents inhibition by both c-Myc
      and E2F1. These studies identify a negative regulatory element within the Zta
      activation domain that is regulated by the cell cycle-promoting factors c-Myc and
      E2F1.

PMID- 15479837
TI  - Transmission study of Andes hantavirus infection in wild sigmodontine rodents.
AB  - Our study was designed to contribute to an understanding of the timing and
      conditions under which transmission of Andes hantavirus in Oligoryzomys
      longicaudatus reservoir populations takes place. Mice were caged in test habitats
      consisting of steel drums containing holding cages, where seronegative rodents
      were exposed to wild seropositive individuals by freely sharing the same cage or
      being separated by a wire mesh. Tests were also performed for potential viral
      transmission to mice from excrement-tainted bedding in the cages. Andes virus
      transmitted efficiently; from 130 attempts with direct contact, 12.3% resulted in
      virus transmission. However, if we consider only those rodents that proved to be
      infectious, from 93 attempts we obtained 16 infected animals (17.2%). Twelve of
      them resulted from intraspecies O. longicaudatus encounters where male mice were
      differentially affected and 4 resulted from O. longicaudatus to Abrothrix
      olivaceus. Experiments using Abrothrix longipilis as receptors were not
      successful. Transmission was not observed between wire mesh-separated animals,
      and mice were not infected from excrement-tainted bedding. Bites seemed not to be
      a requisite for oral transmission. Genomic viral RNA was amplified in two out of
      three saliva samples from seropositive rodents, but it was not detected in urine
      samples obtained by vesicle puncture from two other infected rodents.
      Immunohistochemistry, using antibodies against Andes (AND) hantavirus proteins,
      revealed strong reactions in the lung and salivary glands, supporting the
      possibility of oral transmission. Our study suggests that AND hantavirus may be
      principally transmitted via saliva or saliva aerosols rather than via feces and
      urine.

PMID- 15479838
TI  - Infection of specific dendritic cells by CCR5-tropic human immunodeficiency virus
      type 1 promotes cell-mediated transmission of virus resistant to broadly
      neutralizing antibodies.
AB  - The tropism of human immunodeficiency virus type 1 for chemokine receptors plays
      an important role in the transmission of AIDS. Although CXCR4-tropic virus is
      more cytopathic for T cells, CCR5-tropic strains are transmitted more frequently
      in humans for reasons that are not understood. Phenotypically immature myeloid
      dendritic cells (mDCs) are preferentially infected by CCR5-tropic virus, in
      contrast to mature mDCs, which are not susceptible to infection but instead
      internalize virus into a protected intracellular compartment and enhance the
      infection of T cells. Here, we define a mechanism to explain preferential
      transmission of CCR5-tropic viruses based on their interaction with mDCs and
      sensitivity to neutralizing antibodies. Infected immature mDCs differentiated
      normally and were found to enhance CCR5-tropic but not CXCR4-tropic virus
      infection of T cells even in the continuous presence of neutralizing antibodies.
      Infectious synapses also formed normally in the presence of such antibodies.
      Infection of immature mDCs by CCR5-tropic virus can therefore establish a pool of
      infected cells that can efficiently transfer virus at the same time that they
      protect virus from antibody neutralization. This property of DCs may enhance
      infection, contribute to immune evasion, and could provide a selective advantage
      for CCR5-tropic virus transmission.

PMID- 15479839
TI  - Global analysis of host cell gene expression late during cytomegalovirus
      infection reveals extensive dysregulation of cell cycle gene expression and
      induction of Pseudomitosis independent of US28 function.
AB  - Replication of human cytomegalovirus (CMV) depends on host cell gene products
      working in conjunction with viral functions and leads to a dramatic dysregulation
      of cell cycle gene expression. Comprehensive transcriptional profiling was used
      to identify pathways most dramatically modulated by CMV at late times during
      infection and to determine the extent to which expression of the viral chemokine
      receptor US28 contributed to modulating cellular gene expression. Cells infected
      with the AD169 strain of virus or a fully replication competent US28-deficient
      derivative (RV101) were profiled throughout the late phase of infection (50, 72,
      and 98 h postinfection). Although sensitive statistical analysis showed striking
      global changes in transcript levels in infected cells compared to uninfected
      cells, the expression of US28 did not contribute to these alterations. CMV
      infection resulted in lower levels of transcripts encoding cytoskeletal,
      extracellular matrix, and adhesion proteins, together with small GTPases and
      apoptosis regulators, and in higher levels of transcripts encoding cell cycle,
      DNA replication, energy production, and inflammation-related gene products.
      Surprisingly, a large number of cellular transcripts encoding mitosis-related
      proteins were upmodulated at late times in infection, and these were associated
      with the formation of abnormal mitotic spindles and the appearance of
      pseudomitotic cells. These data extend our understanding of how broadly CMV
      alters the regulation of host cell cycle gene products and highlight the
      establishment of a mitosis-like environment in the absence of cellular DNA
      replication as important for viral replication and maturation.

PMID- 15479840
TI  - Structural and thermodynamic basis for the binding of TMC114, a next-generation
      human immunodeficiency virus type 1 protease inhibitor.
AB  - TMC114, a newly designed human immunodeficiency virus type 1 (HIV-1) protease
      inhibitor, is extremely potent against both wild-type (wt) and multidrug
      resistant (MDR) viruses in vitro as well as in vivo. Although chemically similar
      to amprenavir (APV), the potency of TMC114 is substantially greater. To examine
      the basis for this potency, we solved crystal structures of TMC114 complexed with
      wt HIV-1 protease and TMC114 and APV complexed with an MDR (L63P, V82T, and I84V)
      protease variant. In addition, we determined the corresponding binding
      thermodynamics by isothermal titration calorimetry. TMC114 binds approximately 2
      orders of magnitude more tightly to the wt enzyme (K(d) = 4.5 x 10(-12) M) than
      APV (K(d) = 3.9 x 10(-10) M). Our X-ray data (resolution ranging from 2.2 to 1.2
      A) reveal strong interactions between the bis-tetrahydrofuranyl urethane moiety
      of TMC114 and main-chain atoms of D29 and D30. These interactions appear largely
      responsible for TMC114's very favorable binding enthalpy to the wt protease (
      12.1 kcal/mol). However, TMC114 binding to the MDR HIV-1 protease is reduced by a
      factor of 13.3, whereas the APV binding constant is reduced only by a factor of
      5.1. However, even with the reduction in binding affinity to the MDR HIV
      protease, TMC114 still binds with an affinity that is more than 1.5 orders of
      magnitude tighter than the first-generation inhibitors. Both APV and TMC114 fit
      predominantly within the substrate envelope, a property that may be associated
      with decreased susceptibility to drug-resistant mutations relative to that of
      first-generation inhibitors. Overall, TMC114's potency against MDR viruses is
      likely a combination of its extremely high affinity and close fit within the
      substrate envelope.

PMID- 15479841
TI  - Functional correlation of P-glycoprotein expression and genotype with expression
      of the human immunodeficiency virus type 1 coreceptor CXCR4.
AB  - The aim of this study was to investigate the relationship between lymphocyte P
      glycoprotein (P-gp) expression and genotype in vivo and the expression of
      lymphocyte receptors critical in the life cycle of human immunodeficiency virus
      type 1 (HIV-1), i.e., CD4, CCR5, and CXCR4. Using flow cytometry to quantify each
      membrane receptor/transporter, we demonstrate a highly significant correlation
      between P-gp protein expression and the expression of CXCR4 (rho = 0.874; P <
      0.0001). Furthermore, confocal microscopy showed colocalized expression of CXCR4
      and P-gp in the lymphocyte membrane. This significant relationship was also
      apparent at the mRNA level by use of reverse transcription-PCR (rho = 0.61; P <
      0.005) and was present in both phytohemagglutinin-stimulated and unstimulated
      peripheral blood mononuclear cells. Genotypic analysis of the C3435T single
      nucleotide polymorphism of P-gp confirmed significantly higher levels of P-gp in
      C (range, 2.45 to 11.00 relative fluorescence units [RFU])- than in T (range,
      0.25 to 5.00 RFU)-homozygous individuals (P = 0.0088; 95% confidence interval
      [95% CI], 0.7 to 6.3 RFU). An equivalent association between CXCR4 levels and C
      (range, 12.7 to 44.1 RFU) versus T (range, 3 to 18.9 RFU) genotype was also
      demonstrated (P = 0.0019; 95% CI, 5.4 to 23.7). Functionally, although these
      correlates had no impact on HIV-1 production from either X4- or R5-tropic virus,
      expression correlated significantly with the activity of the HIV-1 protease
      inhibitor (PI) saquinavir for both P-gp (rho = 0.75; P = 0.0019) and CXCR4 (rho =
      0.71; P = 0.0041). This study defines an association between P-gp (expression and
      genotype) and CXCR4 that may have implications for the selection of viral tropism
      and the access of drugs to protease for specific tropic types. The interplay
      between these two proteins may also influence the viral genotypes which escape
      effective chemotherapy and which therefore have the opportunity to evolve
      resistance to PIs.

PMID- 15479842
TI  - Amino acid insertions near Gag cleavage sites restore the otherwise compromised
      replication of human immunodeficiency virus type 1 variants resistant to protease
      inhibitors.
AB  - A variety of amino acid substitutions in the protease and Gag proteins have been
      reported to contribute to the development of human immunodeficiency virus type 1
      (HIV-1) resistance to protease inhibitors. In the present study, full-length
      molecular infectious HIV-1 clones were generated by using HIV-1 variants isolated
      from heavily drug-experienced and therapy-failed AIDS patients. Of six full
      length infectious clones generated, four were found to have unique insertions
      (TGNS, SQVN, AQQA, SRPE, APP, and/or PTAPPA) near the p17/p24 and p1/p6 Gag
      cleavage sites, in addition to the known resistance-related multiple amino acid
      substitutions within the protease. The addition of such Gag inserts mostly
      compromised the replication of wild-type HIV-1, whereas the primary multidrug
      resistant HIV infectious clones containing inserts replicated significantly
      better than those modified to lack the inserts. Western blot analyses revealed
      that the processing of Gag proteins by wild-type protease was impaired by the
      presence of the inserts, whereas that by mutant protease was substantially
      improved. The present study represents the first report clearly demonstrating
      that the inserts seen in the proximity of the Gag cleavage sites in highly multi
      PI resistant HIV-1 variants restore the otherwise compromised enzymatic activity
      of mutant protease, enabling the multi-PI-resistant HIV-1 variants to remain
      replication competent.

PMID- 15479844
TI  - Hepatitis C virus core protein associates with detergent-resistant membranes
      distinct from classical plasma membrane rafts.
AB  - A subpopulation of hepatitis C virus (HCV) core protein in cells harboring full
      length HCV replicons is biochemically associated with detergent-resistant
      membranes (DRMs) in a manner similar to that of markers of classical lipid rafts.
      Core protein does not, however, colocalize in immunofluorescence studies with
      classical plasma membrane raft markers, such as caveolin-1 and the B subunit of
      cholera toxin, suggesting that core protein is bound to cytoplasmic raft
      microdomains distinct from caveolin-based rafts. Furthermore, while both the
      structural core protein and the nonstructural protein NS5A associate with
      membranes, they do not colocalize in the DRMs. Finally, the ability of core
      protein to localize to the DRMs did not require other elements of the HCV
      polyprotein. These results may have broad implications for the HCV life cycle and
      suggest that the HCV core may be a valuable probe for host cell biology.

PMID- 15479843
TI  - Further investigation of simian immunodeficiency virus Vif function in human
      cells.
AB  - Primate lentivirus Vif proteins function by suppressing the antiviral activity of
      the cell-encoded apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like
      (APOBEC) proteins APOBEC3G and APOBEC3F. It has been hypothesized that species
      specific susceptibilities of APOBEC proteins to Vif proteins may help govern the
      transmission of primate lentiviruses to new host species. Consistent with this
      view and with previous results, we report that the Vif proteins of several
      diverse simian immunodeficiency viruses (SIVs) that are not known to infect
      humans are not effective inhibitors of human APOBEC3G or APOBEC3F when assessed
      in transient-transfection experiments. Unexpectedly, this lack of SIV Vif
      function did not prevent the replication of two vif-deficient SIVs (SIVtan and
      SIVmnd1; isolated from tantalus monkeys and mandrills, respectively) in a human T
      cell line, HUT78, that expresses both APOBEC 3G and APOBEC3F, a finding which
      demonstrates that some SIVs are partially resistant to the antiretroviral effects
      of these enzymes irrespective of Vif function. Additional virus replication
      studies also revealed that the Vif protein of SIVtan is, in fact, active in human
      T cells, as it substantially enhanced the replication of its cognate virus and
      human immunodeficiency virus type 1. In sum, we now consider it improbable that
      species-specific restrictions to SIV Vif function can explain the lack of human
      infection with certain SIVs. Instead, our data reveal that the species-specific
      modulation of Vif function is more complex than previously envisioned and that
      additional (as-yet-unidentified) viral or host factors may be involved in
      regulating this dynamic interaction between host and pathogen.

PMID- 15479845
TI  - The ability of chloroquine to prevent tat-induced cytokine secretion by monocytes
      is implicated in its in vivo anti-human immunodeficiency virus type 1 activity.
AB  - Hydroxychloroquine at 1 microM reduces the load of human immunodeficiency virus
      type 1 (HIV-1) in patients, whereas chloroquine (CQ) concentrations above 3
      microM are required for inhibition of HIV-1 replication in peripheral blood
      mononuclear cells. Exogenous HIV-1 Tat reaches the cytosol of T cells by using
      low endosomal pH, and endosome neutralization by CQ prevents Tat from entering
      and affecting T cells. We show here that 0.6 microM CQ inhibits cytokine
      secretion induced by Tat in monocytes without affecting lipopolysaccharide
      triggered cytokine release. This finding suggests that the in vivo anti-HIV-1
      effect of CQ results not from a direct effect on the infected cell but rather
      from the capacity of CQ to prevent Tat from perturbing the cytokine balance.

PMID- 15479846
TI  - APOBEC3G incorporation into human immunodeficiency virus type 1 particles.
AB  - APOBEC3G is promiscuous with respect to its antiretroviral effect, requiring that
      it be packaged into diverse retrovirus particles. Here, we show that most virally
      encoded human immunodeficiency virus type 1 particle components are dispensable
      for APOPEC3G incorporation. However, replacement of the nucleocapsid (NC) Gag
      domain with a leucine zipper abolished APOBEC3G incorporation. Moreover,
      coprecipitation analysis showed that APOBEC3G-Gag interaction requires NC and
      nonspecific RNA. These observations suggest that APOBEC3G exploits an essential
      property of retroviruses, namely, RNA packaging, to infiltrate particles. Because
      it is, therefore, difficult to evolve specific sequences that confer escape from
      APOBEC3G, these findings may explain why lentiviruses evolved an activity that
      induces its destruction.

PMID- 15479847
TI  - Statin compounds reduce human immunodeficiency virus type 1 replication by
      preventing the interaction between virion-associated host intercellular adhesion
      molecule 1 and its natural cell surface ligand LFA-1.
AB  - A variety of host factors, including membrane proteins acquired by human
      immunodeficiency virus type 1 (HIV-1), play a dominant role in HIV-1 adsorption
      onto host cells. Examples include the integrin intercellular adhesion molecule 1
      (ICAM-1), which, once acquired by HIV-1, promotes virus infectivity via ligation
      to LFA-1. We tested the ability of statins to diminish HIV-1 replication, based
      on the idea that these compounds have been shown to block ICAM-1-LFA-1
      interactions. Our data indicate that statins diminish HIV-1 attachment to target
      cells by suppressing ICAM-1-LFA-1 interactions. The capacity of statins to limit
      the initial steps in virus replication could represent an interesting approach
      for the treatment of HIV-1 infection.

PMID- 15479848
TI  - Selection for loss of Ref1 activity in human cells releases human
      immunodeficiency virus type 1 from cyclophilin A dependence during infection.
AB  - Capsid (CA)-specific restrictions are determinants of retroviral tropism in
      mammalian cells. One such restriction, human Ref1, targets strains of murine
      leukemia virus bearing an arginine at CA residue 110 (N-MLV), resulting in
      decreased accumulation of viral cDNA. The cellular factors accounting for Ref1
      activity are unknown. As(2)O(3) increases N-MLV titer in Ref1-positive cells,
      possibly by counteracting Ref1. Restriction factor saturation experiments suggest
      that Ref1 may also target human immunodeficiency virus type 1 (HIV-1), but only
      if its CA is not bound to the cellular protein cyclophilin A (CypA). As a step
      towards understanding the genetic determinants of Ref1, we subjected Ref1
      positive TE671 cells to three sequential rounds of selection with N-MLV reporter
      viruses. We isolated a subclone, 17H1, that was permissive for N-MLV infection
      and therefore deficient in Ref1 activity. Stimulation of N-MLV replication by
      As(2)O(3) was attenuated in 17H1, confirming that the drug acts by overcoming
      Ref1 activity. HIV-1 infection of 17H1 cells was resistant to disruption of the
      CA-CypA interaction, demonstrating that Ref1 restricts CypA-free HIV-1. Our
      results suggest that interaction with CypA evolved to protect HIV-1 from this
      human antiviral activity.

PMID- 15479850
TI  - Differential effects on the hepatitis C virus (HCV) internal ribosome entry site
      by vitamin B12 and the HCV core protein.
AB  - To investigate the role of the hepatitis C virus internal ribosome entry site
      (HCV IRES) domain IV in translation initiation and regulation, two chimeric IRES
      elements were constructed to contain the reciprocal domain IV in the otherwise
      HCV and classical swine fever virus IRES elements. This permitted an examination
      of the role of domain IV in the control of HCV translation. A specific inhibitor
      of the HCV IRES, vitamin B(12), was shown to inhibit translation directed by all
      IRES elements which contained domain IV from the HCV and the GB virus B IRES
      elements, whereas the HCV core protein could only suppress translation from the
      wild-type HCV IRES. Thus, the mechanisms of translation inhibition by vitamin
      B(12) and the core protein differ, and they target different regions of the IRES.

PMID- 15479849
TI  - Mink epithelial cell killing by pathogenic murine leukemia viruses involves
      endoplasmic reticulum stress.
AB  - We previously demonstrated that mink cells undergo apoptosis after MCF13 murine
      leukemia virus (MLV) infection. In this study, we observed that virus-infected
      mink epithelial cells had significantly larger amounts of steady-state levels of
      MCF13 MLV envelope precursor protein (gPr80(env)) than did Mus dunni fibroblasts,
      which are resistant to virus-induced cytopathicity. Infection of mink cells with
      the noncytopathic NZB-9 MLV did not result in the accumulation of gPr80(env).
      MCF13 MLV infection of mink cells produced low cell surface expression of
      envelope glycoprotein and less efficient spread of infectious virus. Western blot
      analysis of mink epithelial cells infected with MCF13 MLV showed an increase in
      GRP78/BiP, which was not observed for either mink cells infected with NZB-9 MLV
      or M. dunni fibroblasts infected with MCF13 MLV. MCF13 MLV infection of mink
      cells also resulted in a significant upregulation of CHOP/GADD153. These results
      indicate that the accumulation of MCF13 MLV gPr80(env) triggers endoplasmic
      reticulum stress, which may mediate apoptosis in mink epithelial cells.

PMID- 15479851
TI  - Low level of lytic replication in a recombinant Epstein-Barr virus carrying an
      origin of replication devoid of BZLF1-binding sites.
AB  - Binding of the BZLF1 viral transactivator to Epstein-Barr virus (EBV) oriLyt has
      been reported to be essential for viral DNA replication. We have constructed a
      recombinant virus (E2-oriLyt-R) in which the oriLyt BZLF1-binding sites (ZRE)
      were exchanged against papilloma E2-binding sites. A fusion protein between the
      BZLF1 protein-transactivating domain and the E2 protein-binding domain was able
      to reactivate lytic replication in E2-oriLyt-R. However, BZLF1 alone could also
      induce E2-oriLyt-R, albeit with much lower efficiency. ZRE are therefore
      important but not absolutely essential cis elements for lytic replication. This
      shows the importance of recombinants to evaluate viral functions.

PMID- 15479852
TI  - Genetic interactions between hepatitis C virus replicons.
AB  - To investigate interactions between hepatitis C virus (HCV) RNA replication
      complexes, a system was developed to simultaneously select different HCV
      subgenomic replicons within the same cell. Transcomplementation of defective
      replicons was not observed, suggesting an isolated and independent nature of the
      HCV RNA replication complex. In contrast, a high level of competition between
      replicons was observed, such that the presence and increased fitness of one
      replicon reduced the capacity of a second one to stably replicate. These results
      suggest that at least one factor in Huh7 cells required for HCV RNA replication
      is limiting and saturable.

PMID- 15479853
TI  - DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and the S
      protein of severe acute respiratory syndrome coronavirus.
AB  - The lectins DC-SIGN and DC-SIGNR can augment viral infection; however, the range
      of pathogens interacting with these attachment factors is incompletely defined.
      Here we show that DC-SIGN and DC-SIGNR enhance infection mediated by the
      glycoprotein (GP) of Marburg virus (MARV) and the S protein of severe acute
      respiratory syndrome coronavirus and might promote viral dissemination. SIGNR1, a
      murine DC-SIGN homologue, also enhanced infection driven by MARV and Ebola virus
      GP and could be targeted to assess the role of attachment factors in filovirus
      infection in vivo.

PMID- 15479854
TI  - Characterization of basolateral chloride/bicarbonate exchange in macula densa
      cells.
AB  - Functional and immunohistological studies were performed to identify basolateral
      chloride/bicarbonate exchange in macula densa cells. Using the isolated, perfused
      thick ascending limb with attached glomerulus preparation dissected from rabbit
      kidney, macula densa intracellular pH (pH(i)) was measured with fluorescence
      microscopy and BCECF. For these experiments, basolateral chloride was reduced,
      resulting in reversible macula densa cell alkalinization. Anion exchange activity
      was assessed by measuring the maximal net base efflux on readdition of bath
      chloride. Anion exchange activity required the presence of bicarbonate, was
      independent of changes in membrane potential, did not require the presence of
      sodium, and was inhibited by high concentrations of DIDS. Inhibition of macula
      densa anion exchange activity by basolateral DIDS increased luminal NaCl
      concentration-induced elevations in pH(i). Immunohistochemical studies using
      antibodies against AE2 demonstrated expression of AE2 along the basolateral
      membrane of macula densa cells of rabbit kidney. These results suggest that
      macula densa cells functionally and immunologically express a
      chloride/bicarbonate exchanger at the basolateral membrane. This transporter
      likely participates in the regulation of pH(i) and might be involved in macula
      densa signaling.

PMID- 15479855
TI  - Ceramide synthase is essential for endonuclease-mediated death of renal tubular
      epithelial cells induced by hypoxia-reoxygenation.
AB  - Ceramide is known to play a role in the cell signaling pathway involved in
      apoptosis. Most studies suggest that enhanced ceramide generation is the result
      of hydrolysis of sphingomyelin by sphingomyelinases. However, the role of
      ceramide synthase in enhanced ceramide generation has not been previously
      examined in hypoxia-reoxygenation injury. In the present study, we demonstrated
      that 60-min hypoxia of rat renal tubular epithelial NRK-52E cells in a gas
      chamber with 95% N2-5% CO2 with glucose deprivation resulted in a significant
      increase in ceramide generation. The ceramide level further increased after
      reoxygenation for 60 min. Exposure of cells to hypoxia-reoxygenation resulted in
      a significant increase in ceramide synthase activity without any significant
      change in acid or neutral sphingomyelinase. The hypoxia-reoxygenation of NRK-52E
      cells was also associated with the release of endonuclease G (EndoG) from
      mitochondria to cytoplasm measured by Western blot analysis and endonuclease
      activity assay. It further led to the fragmentation of DNA and cell death. A
      specific inhibitor of ceramide synthase, fumonisin B1 (50 microM), suppressed
      hypoxia-reoxygenation-induced ceramide generation and provided protection against
      hypoxia-reoxygenation-induced EndoG release, DNA fragmentation, and cell death.
      Taken together, our data suggest that hypoxia-reoxygenation results in an
      activation of ceramide synthase rather than sphingomyelinase and that ceramide
      synthase-dependent ceramide generation is a key modulator of EndoG-mediated
      cytotoxicity in hypoxia-reoxygenation injury to renal tubular epithelial cells.

PMID- 15479856
TI  - Interactions of TGF-dependent and myogenic oscillations in tubular pressure.
AB  - We have previously shown that there are two oscillating components in
      spontaneously fluctuating single-nephron blood flow obtained from Sprague-Dawley
      rats (Yip K-P, Holstein-Rathlou NH, and Marsh DJ. Am J Physiol Renal Physiol 264:
      F427-F434, 1993). The slow oscillation (20-30 mHz) is mediated by
      tubuloglomerular feedback (TGF), whereas the fast oscillation (100 mHz) is
      probably related to spontaneous myogenic activity. The fast oscillation is rarely
      detected in spontaneous tubular pressure because of its small magnitude and the
      fact that tubular compliance filters pressure waves. We detected myogenic
      oscillation superimposed on TGF-mediated oscillation when ambient tubular flow
      was interrupted. Two well-defined peaks are present in the mean power spectrum of
      stop-flow pressure (SFP) centering at 25 and 100 mHz (n = 13), in addition to a
      small peak at 125-130 mHz. Bispectral analysis indicates that two of these
      oscillations (30 and 100 mHz) interact nonlinearly to produce the third
      oscillation at 125-130 mHz. The presence of nonlinear interactions between TGF
      and myogenic oscillations indicates that estimates of the relative contribution
      of each of these mechanisms in renal autoregulation need to account for this
      interaction. The magnitude of myogenic oscillations was considerably smaller in
      the SFP measured from spontaneously hypertensive rats (SHR, n = 13);
      consequently, nonlinear interactions were not observed with bispectral analysis.
      Reduced augmentation of myogenic oscillations in SFP of SHR might account for the
      failure in detecting nonlinear interactions in SHR.

PMID- 15479858
TI  - Role of protein methylation in regulation of transcription.
AB  - In the last few years, the discovery of lysine and arginine methylation in
      histones and other proteins and the enzymes that carry out these
      posttranslational modifications has added a new dimension to the signal
      transduction field. In particular, there has been a huge surge in our
      understanding of how methylation of nucleosomal histones at specific lysine or
      arginine residues affects chromatin conformations and either facilitates or
      inhibits transcription from neighboring genes. It appears that the responsible
      methyltransferases can be targeted in some cases to specific genes and in other
      cases to broader regions of euchromatin or heterochromatin. Methylation of
      histones is mechanistically linked to other types of histone modifications, such
      as acetylation, phosphorylation, and monoubiquitylation; combinations of these
      modifications cooperate to regulate chromatin structure and transcription by
      stimulating or inhibiting binding of specific proteins. Although lysine
      methylation has thus far been observed almost exclusively on histones, arginine
      methylation has been observed on a variety of other proteins associated with gene
      regulation, including DNA-binding transcriptional activators, transcriptional
      coactivators, and many RNA binding proteins involved in RNA processing,
      transport, and stability. Thus, lysine and arginine methylation of proteins, like
      many other types of posttranslational modifications, are regulated steps of many
      specific signaling pathways.

PMID- 15479859
TI  - Polymorphisms in the osteopontin promoter affect its transcriptional activity.
AB  - Understanding the molecular mechanisms that underlie regulation of transcription
      of the human osteopontin encoding gene (OPN) may help to clarify several
      processes, such as fibrotic evolution of organ damage, tumorigenesis and
      metastasis, and immune response, in which OPN overexpression is observed. With
      the aim to evaluate variants with functional effect on transcription, we have
      analyzed the promoter region and focused our investigation on three common
      variants present in the first 500 bp upstream of the transcription start site.
      Transfection of constructs carrying the four most frequent haplotypes relative to
      variants at -66, -156, and -443 fused to the luciferase reporter gene in a panel
      of different cell lines showed that one haplotype conferred a significantly
      reduced level of reporter gene expression in all tested cell lines. We describe
      that the -66 polymorphism modifies the binding affinity for the SP1/SP3
      transcription factors, the -156 polymorphism is included in a yet uncharacterized
      RUNX2 binding site, and the -443 polymorphism causes differential binding of an
      unknown factor. The finding of differential effects of various combination of
      variants in haplotypes may contribute to explain data of association studies
      reported in several already published articles. Future association studies using
      haplotypes instead of single OPN variants will allow to achieve more accurate
      results referable to differential expression of OPN in several common diseases,
      in which OPN is considered a candidate susceptibility gene.

PMID- 15479861
TI  - Expanded nuclear roles for IkappaBs.
AB  - I kappa B (IkappaB) was initially identified as a factor that inhibits DNA
      binding and nuclear translocation of the transcription factor nuclear factor
      kappa B (NF-kappaB). Recently, however, IkappaB family members have demonstrated
      direct nuclear roles in regulating NF-kappaB-dependent transcription. Some
      IkappaB proteins, including IkappaBalpha and IkappaBbeta, can regulate
      transcription by modulating the concentration of active NF-kappaB complexes
      within the nucleus. Others, such as IkappaBzeta and Bcl-3, can directly activate
      transcription by forming transcriptional complexes at gene promoters. Thus,
      IkappaB proteins play important nuclear roles in regulating NF-kappaB-dependent
      transcription after stimulation with various extracellular signals.

PMID- 15479860
TI  - Transcriptional reprogramming and ultrastructure during atrophy and recovery of
      mouse soleus muscle.
AB  - This study investigated the use of the hindlimb suspension (HS) and reloading
      model of mice for the mapping of ultrastructural and gene expressional
      alterations underlying load-dependent muscular adaptations. Mice were hindlimb
      suspended for 7 days or kept as controls (n = 12). Soleus muscles were harvested
      after HS (HS7, n = 23) or after resuming ambulatory cage activity (reloading) for
      either 1 day (R1, n = 13) or 7 days (R7, n = 9). Using electron microscopy, a
      reduction in mean fiber area (-37%) and in capillary-to-fiber ratio (from 1.83 to
      1.42) was found for HS7. Subsequent reloading caused an increase in interstitial
      cells (+96%) and in total capillary length (+57%), whereas mean fiber area and
      capillary-to-fiber ratio did not significantly change compared with HS. Total RNA
      in the soleus muscle was altered with both HS (-63%) and reloading (+108% in R7
      compared with control). This is seen as an important adaptive mechanism. Gene
      expression alterations were assessed by a muscle-specific low-density cDNA
      microarray. The transcriptional adjustments indicate an early increase of
      myogenic factors during reloading together with an overshoot of contractile (MyHC
      I and IIa) and metabolic (glycolytic and oxidative) mRNA amounts and suggest
      mechano-sensitivity of factors keeping the sarcomeres in register (desmin, titin,
      integrin-beta1). Important differences to published data from former rat studies
      were found with the mouse HS model for contractile and glycolytic enzyme
      expression. These species-specific differences need to be considered when
      transgenic mice are used for the elucidation of monogenetic factors in mechano
      dependent muscle plasticity.

PMID- 15479862
TI  - Migrate, differentiate, proliferate, or die: pleiotropic functions of an apical
      "apoptotic caspase".
AB  - Caspases, the cysteine proteases that cleave their substrates following an
      aspartate residue, primarily carry out two distinct functions: (i) activation of
      proinflammatory cytokines and (ii) execution of apoptosis. These two functions
      are considered to be unique to individual caspases; thus, some caspases act in
      apoptosis, whereas others have a role in inflammation. However, this dogma is now
      being challenged as nonapoptotic functions are ascribed to caspases that, until
      recently, were only known to function in cell death pathways. Recent work
      suggests that DRONC, the only initiator cell death caspase in Drosophila, may
      play a direct or indirect role in cell migration, sperm differentiation, and cell
      proliferation in addition to its function in cell death.

PMID- 15479863
TI  - Advances in Targeted Therapies VI. Proceedings of the 6th International
      Symposium. Venice, Italy, 28 April-2 May 2004.

PMID- 15479864
TI  - Why results of clinical trials and observational studies of antitumour necrosis
      factor (anti-TNF) therapy differ: methodological and interpretive issues.
AB  - OBJECTIVE: Results of randomised clinical trials (RCTs) appear to differ from
      results of observational studies. This paper explores differences in methodology,
      interpretation and presentation of results that elucidate these differences.
      METHOD: We identified patients who completed a survey questionnaire during the
      period January 1998 through December 1998 and also completed one between July
      2003 and June 2004, an average span of 4.7 years. The mean time from study
      initiation to anti-TNF administration was 2.1 years, and the mean treatment time
      was 2.1 (SD 1.3) years at study closure. During this period 38.3% of patients
      received anti-TNF therapy. We compared the results of patients in this group with
      results from RCTs. RESULTS: RCTs utilise flare design, patient selection, control
      groups and regression to the mean. Observational studies, on the other hand,
      confound additional prior therapy and anti-TNF effect, do not employ control
      groups, and may have less regression to the mean. CONCLUSIONS: RCTs and
      observational studies assess and report efficacy and effectiveness in ways that
      are so different that they are often incommensurable. A key difference is whether
      results should represent changes from flare states or should, instead, consider
      chronic status prior to initiation of therapy. There is little evidence that the
      clinical state at the start of most anti-TNF RCTs represents a chronic state.
      Economic analyses that utilise the RCT starting point overestimate the cost
      effectiveness of anti-TNF therapy. The solution for these problems and a guide to
      understanding the real results of anti-TNF therapy lies in collecting preclinical
      trial data in all patients who will enter clinical trials. In addition, RCT
      results would more approximate those of observational studies if all reporting
      was done after subtracting the effect of the comparator group.

PMID- 15479865
TI  - Safety of antitumour necrosis factor (anti-TNF) therapy in patients with chronic
      viral infections: hepatitis C, hepatitis B, and HIV infection.
AB  - Tumour necrosis factor alpha (TNFalpha) is a pivotal cytokine in host defences
      with broad ranging effects on the innate and adaptive immune systems. Clinically,
      TNFalpha inhibitors have demonstrated remarkable efficacy in a wide range of
      autoimmune and inflammatory disorders but clearly at the cost of heightened
      susceptibility to a variety of infections in those treated with these agents.
      Most reports to date have described increased susceptibility to intracellular
      pathogens in patients with underlying chronic viral infections, but little in the
      way of adverse event reporting in these patients has occurred. While the reported
      experience to date is rather limited, TNFalpha inhibitors have displayed a
      reasonable safety profile in the setting of some chronic viral infections and in
      certain circumstances have demonstrated adjunctive activity in the treatment of
      these infections. Given the high prevalence of chronic viral infections in
      patients who are candidates for anti-TNF therapy and the potential for these
      agents in the treatment of chronic viral illness, additional studies are urgently
      needed to assess the risks and benefits of such therapy in these populations.

PMID- 15479867
TI  - Pharmacogenetics in the rheumatic diseases.

PMID- 15479866
TI  - Updated consensus statement on biological agents, specifically tumour necrosis
      factor alpha (TNFalpha) blocking agents and interleukin-1 receptor antagonist (IL
      1ra), for the treatment of rheumatic diseases, 2004.

PMID- 15479868
TI  - What precedes development of rheumatoid arthritis?
AB  - Studies on aetiology of inflammatory diseases such as rheumatoid arthritis (RA)
      need to investigate the potential environmental triggers that are active before
      onset of disease, the genetic context in which these triggers act, and whether
      the presence of such triggers in an arthritis prone genetic context will give
      rise to the immune reactions associated with/preceding RA. Such knowledge would
      help not only to address much better the issue of causality of these potential
      triggers and the immune reactions, but also to carry out various interventions
      aimed at influencing the disease provoking immune events before development of
      clinical signs of disease. This short report summarises recent data demonstrating
      (a) the presence of anticitrullin antibodies or rheumatoid factors in between a
      third and half of patients with RA before development of clinical signs; (b) long
      term smoking is associated with a high risk of future development of seropositive
      but not seronegative RA; and (c) a strong gene-environment interaction between
      smoking and SE genes in the development of seropositive RA. We conclude that, in
      a certain genetic context, smoking is a potential trigger of RA, and a
      combination of the two factors is associated with the occurrence of immune
      reactions long before the onset of RA.

PMID- 15479869
TI  - Should contemporary rheumatoid arthritis clinical trials be more like standard
      patient care and vice versa?
AB  - The information used by rheumatologists when delivering care to patients with
      rheumatoid arthritis (RA) is derived mainly from two sources: randomised
      controlled clinical trials and experience in clinical care. However, these two
      sources differ significantly because (a) the extensive inclusion and exclusion
      criteria result in clinical trial participants being recruited from only a
      minority of patients seen in standard clinical care; (b) assessments in clinical
      trials are conducted according to standard quantitative measures and indices,
      while standard clinical care of most patients with RA is generally conducted
      empirically, without collection of any quantitative data other than laboratory
      tests to estimate prognosis and document change in status; and (c) although
      baseline databases of various clinical trials (and observational studies) are 60
      90% identical in content, they are not standardised and therefore not amenable to
      direct comparisons. Strategies to promote similarities between clinical trials
      and standard clinical care in patients with RA may include: more generalised
      inclusion criteria; incorporation of quantitative measurement into standard care,
      easily accomplished by asking each patient to complete a simple questionnaire at
      each visit to a rheumatologist; and consensus among rheumatologists for databases
      with standard content and format in clinical care and research involving patients
      with RA.

PMID- 15479870
TI  - The International Classification of Functioning, Disability and Health (ICF) Core
      Sets for rheumatoid arthritis: a way to specify functioning.
AB  - Today, patients' functioning is a central issue in medicine. Concepts,
      classifications, and measurements of functioning and health, such as the
      International Classification of Functioning, Disability and Health (ICF) are of
      prime importance in clinical practice, teaching, and research. This report
      compares the contents of three of the most widely used health status measures in
      rheumatoid arthritis (RA), namely the Health Assessment Questionnaire disability
      index (HAQ), the Arthritis Impact Measurement Scales 2 (AIMS2), and the Short
      Form health survey (SF-36) based on the ICF. In addition, their content is
      compared to the Comprehensive ICF Core Set for RA. The comparisons illustrate
      that the different health status measures cover different components, and that
      they cover the different components with different level of precision. Using the
      ICF as a reference framework allows a researcher or a recommending instance to
      see which domains are covered in a specific instrument and, therefore, whether it
      is necessary to complement the study with other measures. Nevertheless, which
      specific health status measures to recommend still remains a challenge. If enough
      care is taken to define "what should be measured", it could form the basis for a
      solid and stable recommendation, adhered to for many years.

PMID- 15479871
TI  - Should infection still be considered as the most likely triggering factor for
      rheumatoid arthritis?

PMID- 15479872
TI  - New issues in tuberculosis.
AB  - Tuberculosis remains a major health problem worldwide. The disease is caused by
      Mycobacterium tuberculosis whose preferred habitat is the host macrophage. The
      immune response against tuberculosis is mediated by different subsets of T cells
      including both conventional CD4 and CD8 T cells as well as unconventional CD1
      restricted and gammadelta T cells. The CD1 restricted T cells are particularly
      remarkable because they recognise the glycolipids abundant in the mycobacterial
      cell wall. Although a vaccine, M.bovis BCG, is available which protects toddlers
      against miliary tuberculosis, it is ineffective in preventing pulmonary
      tuberculosis in adults. Therefore, a novel vaccine is urgently required.
      Knowledge about the functioning of different T cell populations during infection
      and disease provides the basis for rational vaccine design. We have constructed a
      recombinant BCG vaccine which, compared with wild-type BCG, induces superior
      protection not only against laboratory strains but also against clinical isolates
      of M. tuberculosis.

PMID- 15479873
TI  - Nuclear factor (NF)-kappaB proteins: therapeutic targets.

PMID- 15479874
TI  - Mitogen activated protein kinases as targets for development of novel anti
      inflammatory drugs.
AB  - Given the prevalence and debilitating nature of chronic inflammatory diseases
      there is a never ending quest for identification of novel targets for the
      rational development of anti-inflammatory drugs. Although the major signalling
      pathway that controls inflammation associated gene expression is the one leading
      to activation of transcription factor NF-kappaB, considerable attention has also
      been given to mitogen activated protein kinases (MAPKs) as likely targets for
      development of novel anti-inflammatory therapeutics. Indeed, inhibitors targeting
      these pathways have been developed and preliminary preclinical data suggest that
      they exhibit anti-inflammatory activity. This report focuses on the possible
      mechanisms through which such inhibitors may interfere with inflammation and
      discusses the pros and cons of targeting MAPKs in the treatment of chronic
      inflammatory disease.

PMID- 15479875
TI  - B cell signalling as therapeutic target.

PMID- 15479876
TI  - Targeting the Jak/STAT pathway for immunosuppression.

PMID- 15479877
TI  - DREAMing about arthritic pain.
AB  - The experience of acute pain serves a crucial biological purpose: it alerts a
      living organism to environmental dangers, inducing behavioural responses which
      protect the organism from further damage. In contrast, chronic pain arising from
      disease states and/or pathological functioning of the nervous system offers no
      advantage and may be debilitating to those afflicted. Despite recent advances in
      our understanding of pain mechanisms, the satisfactory management of pathological
      pain eludes current treatment strategies. We have demonstrated in a previous
      study on dream deficient mice the pivotal role of downstream regulatory element
      antagonistic modulator (DREAM) in modulating pain sensitivity in a number of
      behavioural models, including acute and chronic neuropathic pain. DREAM is a
      novel calcium binding transcriptional repressor for the prodynorphin gene in
      spinal cord neurones. The marked attenuation in pain behaviour exhibited by dream
      /- mice was shown, by pharmacological and biochemical analyses, to be due to
      increased activation of the endogenous kappa-opioid system. Importantly, loss of
      DREAM also attenuated inflammatory pain. Thus, DREAM and the DREAM pathway
      constitute a novel therapeutic paradigm for the treatment of chronic pain in
      arthritis.

PMID- 15479878
TI  - A toll for T cell costimulation.

PMID- 15479879
TI  - The utility of tumour necrosis factor blockade in orphan diseases.
AB  - A variety of rheumatic disorders have been successfully treated with tumour
      necrosis factor (TNF) blockers. However, TNF blockade may be useful in a number
      of rare diseases. Preliminary data suggest that several forms of vasculitis
      appear responsive to TNF antagonists-Behcet's disease, Churg-Strauss vasculitis,
      polyarteritis nodosa, and giant cell arteritis, among others. Wegener's
      granulomatosis and sarcoidosis have been shown to improve with infliximab but not
      with etanercept. These results lend further support for the concept of
      differential mechanism(s) of action of the two antagonists with infliximab being
      more effective for the treatment of granulomatous diseases.
      Polymyositis/dermatomyositis may also be responsive to TNF blockade. TNF likely
      plays little role in Sjogren's syndrome as evidenced by the lack of efficacy of
      both TNF antagonists. Etanercept has been shown to be useful in the treatment of
      hepatitis C both in reducing the viral load and improving liver function. A
      number of other more rare disorders also may be responsive to TNF blockade.
      Further studies with larger numbers of well characterised patients and treatment
      regimens are necessary to provide more definitive evidence of the utility of the
      TNF antagonists in these serious and often life threatening diseases.

PMID- 15479880
TI  - Chemokines: role in inflammation and immune surveillance.
AB  - Chemotactic migration of leucocytes largely depends on adhesive interaction with
      the substratum and recognition of a chemoattractant gradient. Both aspects, cell
      adhesion and chemotaxis, are regulated by members of the family of chemotactic
      cytokines (chemokines) comprising structurally related and secreted proteins of
      67-127 amino acids in length. Breakdown in the control of leucocyte mobilisation
      contributes to chronic inflammatory diseases and, hence, interference with
      chemokine function is a promising approach for the development of novel anti
      inflammatory medication. Chemokines target all types of leucocyte, including
      haematopoietic precursors, mature leucocytes of the innate immune system as well
      as naive, memory, and effector lymphocytes. The combinatorial diversity in
      responsiveness to chemokines ensures proper tissue distribution of distinct
      leucocyte subsets under normal and inflammatory/pathological conditions. Here, we
      discuss recent views on the role of chemokines in controlling tissue localisation
      of human memory T cells under steady state (non-inflamed) conditions. Emphasis is
      placed on a concept describing distinct subsets of memory T cells according to
      their primary residence in peripheral blood, secondary lymphoid tissues, or
      peripheral (extralymphoid) tissues.

PMID- 15479881
TI  - Toll-like receptors in rheumatoid arthritis joint destruction mediated by two
      distinct pathways.

PMID- 15479882
TI  - Defining a role for fibroblasts in the persistence of chronic inflammatory joint
      disease.
AB  - The most surprising feature of the inflammatory response in rheumatoid arthritis
      is not that it occurs but that it does not resolve. The persistence of the
      chronic inflammatory response in conjunction with ongoing joint destruction is an
      all too familiar finding in many patients with rheumatoid arthritis. Despite the
      use of effective anti-inflammatory agents and disease modifying drugs, a
      significant proportion of patients with rheumatoid arthritis continue to have
      resistant disease. Complete clinical remission is unusual for more than six
      months and a formal cure of the disease remains elusive. In this report we focus
      on how attempts to address the question of why rheumatoid arthritis persists have
      led to a different interpretation of the pathogenesis of rheumatoid disease; one
      in which alterations in stromal cells such as fibroblasts play an important role
      in the switch from resolving to persistent disease.

PMID- 15479883
TI  - Cell therapy for autoimmune diseases: does it have a future?
AB  - Almost all current therapeutic concepts in autoimmune diseases are based on the
      systemic suppression of immune functions and are not curative. The recent
      introduction of biologicals such as tumour necrosis factor blocking antibodies or
      receptors has added greater specificity to efficient management of disease by
      targeted suppression of rheumatic inflammation. It is evident, however, that only
      the elimination of the cells secreting inflammatory mediators, rather than the
      blockade of secreted molecules, will offer real specific therapeutic advantages
      in the future. Merely the elimination of such cells and also cells controlling
      the secreting effector cells could be curative and induce true long term
      remissions. We review here the state of the art and future therapeutic concepts
      that are based on the specific modulation of pathogenic cells that induce and
      sustain autoimmune inflammation. This sounds visionary, however, a variety of
      basic tools are at hand now. Thus, direct and specific cell therapy of rheumatic
      diseases will become a true alternative to conventional therapies.

PMID- 15479884
TI  - Dynamic exercises in patients with rheumatoid arthritis.

PMID- 15479885
TI  - Predictive factors of work disability in rheumatoid arthritis: a systematic
      literature review.
AB  - BACKGROUND: Work disability-a common outcome of rheumatoid arthritis (RA)-is a
      societal (for example, financial costs) and individual problem (for example, loss
      of status, income, social support, and distraction from pain and distress). Until
      now, factors that predict work disability in RA have not been systematically
      reviewed. OBJECTIVE: To determine predictive factors of work disability in RA as
      reported in the literature. METHODS: A systematic literature search in Cinahl
      (1988-2004), Embase (1988-2004), and Medline (1989-2004) was followed by the
      application of two sets of criteria related to: (a) methodological quality, and
      (b) measurement of the predictive factor. Based on the quality and the
      consistency of the findings, a rating system was used to assess the level of
      evidence for each predictive factor. RESULTS: Nineteen publications (17 cohorts)
      were identified, of which 13 met the general methodological quality criteria.
      Results provided strong evidence that physical job demands, low functional
      capacity, old age, and low education predict work disability in RA. Remarkably,
      biomedical variables did not consistently predict work disability. Moreover,
      owing to the lack of high quality studies no evidence was found for personal
      factors such as coping style, and work environmental factors such as work
      autonomy, support, work adjustments that are presumed crucial in the work
      disablement process. CONCLUSIONS: The results indicate that work disability in RA
      is a biopsychosocially determined misfit between individual capability and work
      demands.

PMID- 15479886
TI  - Interleukin (IL) 18 stimulates osteoclast formation through synovial T cells in
      rheumatoid arthritis: comparison with IL1 beta and tumour necrosis factor alpha.
AB  - OBJECTIVE: To determine whether IL18 has any indirect effects on
      osteoclastogenesis mediated by T cells in RA synovium, and compare its effects
      with those of IL1 beta and TNF alpha. METHODS: Resting T cells were isolated from
      peripheral blood of healthy donors, and stimulated with 2 microg/ml
      phytohaemagglutinin (PHA) and 0.5 ng/ml IL2 for 24 hours. Synovial T cells were
      isolated from RA synovial tissue. The levels of soluble receptor activator of the
      NF-kappa B ligand (RANKL), osteoprotegerin (OPG), IFN gamma, M-CSF, and GM-CSF
      were determined by ELISA. Membrane bound RANKL expression was analysed by flow
      cytometry. Commercially available human osteoclast precursors were cocultured
      with T cells to induce osteoclast formation, which was determined with tartrate
      resistant acid phosphatase staining and pit formation assay. RESULTS: In PHA
      prestimulated T cells or RA synovial T cells, IL18, IL1 beta, or TNFalpha
      increased soluble RANKL production and membrane bound RANKL expression in a dose
      dependent manner. IL18, IL1 beta, and TNF alpha did not induce M-CSF, GM-CSF, IFN
      gamma, or OPG production in PHA prestimulated T cells or RA synovial T cells.
      IL18 increased the number of osteoclasts and bone resorption area on dentine
      slices in the coculture of human osteoclast precursors with PHA prestimulated T
      cells or RA synovial T cells; its ability was equivalent to that of IL1 beta, but
      less potent than that of TNF alpha. In the coculture system, OPG completely
      blocked osteoclast induction by IL18 or IL1 beta, and greatly inhibited induction
      by TNF alpha. CONCLUSION: IL18, IL1 beta, or TNF alpha can indirectly stimulate
      osteoclast formation through up regulation of RANKL production from T cells in RA
      synovitis; IL18 is as effective as IL1 beta, but less potent than TNF alpha.

PMID- 15479887
TI  - A gene expression signature for recent onset rheumatoid arthritis in peripheral
      blood mononuclear cells.
AB  - BACKGROUND: In previous studies the presence of a distinct gene expression
      pattern has been shown in peripheral blood cells from patients with autoimmune
      disease. OBJECTIVE: To determine whether other specific signatures might be used
      to identify subsets of these autoimmune diseases and whether gene expression
      patterns in early disease might identify pathogenetic factors. METHODS:
      Peripheral blood mononuclear cells were acquired from patients with rheumatoid
      arthritis (RA) and analysed by microarrays containing over 4300 named human
      genes. Patients with RA for <2 years were compared with subjects with
      longstanding RA (average duration 10 years) and with patients with other immune
      or autoimmune diagnoses. RESULTS: Cluster analyses permitted separation of the
      patients with early RA (ERA) from those with longstanding disease. Comparison
      with other patient groups suggested that the ERA signature showed some overlap
      with that seen in the normal immune response to viral antigen as well as with a
      subset of patients with systemic lupus erythematosus. CONCLUSIONS: The ERA
      signature may reflect, in part, a response to an unknown infectious agent.
      Furthermore, shared features with some lupus patients suggest that common
      aetiological factors and pathogenetic pathways may be involved in these two
      autoimmune disorders.

PMID- 15479888
TI  - Synovial tissue interleukin-18 expression and the response to treatment in
      patients with inflammatory arthritis.
AB  - OBJECTIVE: To measure synovial tissue interleukin-18 (IL-18) expression in
      patients with inflammatory arthritis, and to identify associations with serum
      levels, disease activity, and response to treatment. METHODS: Synovial tissue
      biopsies and serum samples were obtained from patients with early, active,
      rheumatoid arthritis (RA) (n = 12), undifferentiated seronegative arthritis (SnA)
      (n = 9), psoriatic arthritis (PsA) (n = 5), and reactive arthritis (ReA) (n = 2)
      before and one year after introduction of disease modifying antirheumatic drug
      (DMARD) treatment. Osteoarthritis (OA) tissues were compared. Tissue IL-18
      expression was determined after immunohistochemical staining using a
      semiquantitative scale. Serum IL-18 was measured by enzyme linked immunosorbent
      assay. RESULTS: Before treatment was started, tissue IL-18 expression was
      increased in each diagnostic group compared with OA (p<0.05). Tissue IL-18
      expression was correlated with serum C reactive protein levels (r = 0.53, p =
      0.003) but not with serum IL-18. After DMARD treatment, 12 patients (five RA,
      four SnA, three PsA) were re-evaluated. Decreases in tissue IL-18 expression were
      observed in eight, although the trend did not reach significance (p = 0.068).
      Changes in tissue IL-18 expression were correlated with changes in serum IL-18 (r
      = 0.62, p = 0.041) and C reactive protein (r = 0.72, p = 0.009). CONCLUSIONS:
      Synovial tissue IL-18 expression was correlated with disease activity in
      inflammatory arthritis. After treatment, tissue levels changed in parallel with
      changes in serum IL-18 and with changes in the acute phase response. These
      observations support a role for IL-18 in the pathophysiology of inflammatory
      arthritis.

PMID- 15479889
TI  - Long term high intensity exercise and damage of small joints in rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate the effect of long term high intensity weightbearing
      exercises on radiological damage of the joints of the hands and feet in patients
      with rheumatoid arthritis (RA). METHODS: Data of the 281 completers of a 2 year
      randomised controlled trial comparing the effects of usual care physical therapy
      (UC) with high intensity weightbearing exercises were analysed for the rate of
      radiological joint damage (Larsen score) of the hands and feet. Potential
      determinants of outcome were defined: disease activity, use of drugs, change in
      physical capacity and in bone mineral density, and attendance rate at exercise
      sessions. RESULTS: After 2 years, the 136 participants in high intensity
      weightbearing exercises developed significantly less radiological damage than the
      145 participants in UC. The mean (SD) increase in damage was 3.5 (7.9) in the
      exercise group and 5.7 (10.2) in the UC group, p = 0.045. Separate analysis of
      the damage to the hands and feet suggests that this difference in rate of
      increase of damage is more pronounced in the joints of the feet than in the
      hands. The rate of damage was independently associated with less disease
      activity, less frequent use of glucocorticoids, and with an improvement in
      aerobic fitness. CONCLUSION: The progression of radiological joint damage of the
      hands and feet in patients with RA is not increased by long term high intensity
      weightbearing exercises. These exercises may have a protective effect on the
      joints of the feet.

PMID- 15479890
TI  - HLA-DR-DQ haplotypes and genotypes in Finnish patients with rheumatoid arthritis.
AB  - OBJECTIVES: To elucidate the contribution of HLA-DR-DQ haplotypes and their
      genotypic combinations to susceptibility to rheumatoid arthritis, and to evaluate
      the various models for HLA associated risk for the disease in a series of Finnish
      patients. METHODS: 322 Finnish patients with rheumatoid arthritis were typed for
      common north European HLA-DR-DQ haplotypes and compared with a series of 1244
      artificial family based control haplotypes. RESULTS: The association of the so
      called shared epitope (SE) haplotypes (DRB1*0401, *0404, *0408, and *01) with
      rheumatoid arthritis was confirmed. The DRB1*0401 haplotypes carried a far
      stronger risk for the disease than the (DRB1*01/10)-(DQA1*01)-DQB1*0501
      haplotypes. Seven protective HLA haplotypes--(DRB1*15)-(DQA1*01)-DQB1*0602;
      (DRB1*08)-(DQA1*04)-DQB1*04; (DRB1*11/12)-DQA1*05-DQB1*0301; (DRB1*1301)
      (DQA1*01)-DQB1*0603; (DRB1*1302)-(DQA1*01)-DQB1*0604; (DRB1*07)-DQA1*0201
      DQB1*0303; and (DRB1*16)- (DQA1*01)-DQB1*0502--were identified. In accordance
      with the reshaped shared epitope hypothesis, all the protective DRB1 alleles in
      these haplotypes share either isoleucine at position 67 or aspartic acid at
      position 70 in their third hypervariable region motif. However, differences in
      the disease risk of haplotypes carrying the same DR but different DQ alleles were
      also found: (DRB1*07)-DQA1*0201-DQB1*0303 was protective, while (DRB1*07)
      DQA1*0201-DQB1*02 was neutral. The same haplotypes carried different risks for
      rheumatoid arthritis depending on their combination in genotypes. CONCLUSIONS:
      When assessing the influence of HLA genes on the susceptibility to rheumatoid
      arthritis, not only should the HLA-DR or -DQ alleles or haplotypes be unravelled
      but also the genotype. The effect of HLA class II region genes is more
      complicated than any of the existing hypotheses can explain.

PMID- 15479891
TI  - Validity and reliability of three definitions of hip osteoarthritis: cross
      sectional and longitudinal approach.
AB  - OBJECTIVES: To compare the reliability and validity in a large open population of
      three frequently used radiological definitions of hip osteoarthritis (OA):
      Kellgren and Lawrence grade, minimal joint space (MJS), and Croft grade; and to
      investigate whether the validity of the three definitions of hip OA is sex
      dependent. METHODS:  SUBJECTS: from the Rotterdam study (aged > or= 55 years, n =
      3585) were evaluated. The inter-rater reliability was tested in a random set of
      148 x rays. The validity was expressed as the ability to identify patients who
      show clinical symptoms of hip OA (construct validity) and as the ability to
      predict total hip replacement (THR) at follow up (predictive validity). RESULTS:
      Inter-rater reliability was similar for the Kellgren and Lawrence grade and MJS
      (kappa statistics 0.68 and 0.62, respectively) but lower for Croft's grade (kappa
      statistic, 0.51). The Kellgren and Lawrence grade and MJS showed the strongest
      associations with clinical symptoms of hip OA. Sex appeared to be an effect
      modifier for Kellgren and Lawrence and MJS definitions, women showing a stronger
      association between grading and symptoms than men. However, the sex dependency
      was attributed to differences in height between women and men. The Kellgren and
      Lawrence grade showed the highest predictive value for THR at follow up.
      CONCLUSIONS: Based on these findings, Kellgren and Lawrence still appears to be a
      useful OA definition for epidemiological studies focusing on the presence of hip
      OA.

PMID- 15479892
TI  - Weight changes and the risk of knee osteoarthritis requiring arthroplasty.
AB  - OBJECTIVE: To examine the effect of weight changes between 20 and 50 years of age
      on the risk of severe knee osteoarthritis (OA) requiring arthroplasty. SUBJECTS
      AND METHODS: Cases were 55-75 year old men and women (n = 220) having had knee
      arthroplasty for primary osteoarthritis at the Kuopio University Hospital in 1992
      93. Controls (n = 415) were randomly selected from the population of Kuopio
      Province. Weight at the age of 20, 30, 40, and 50 years was collected
      retrospectively with a postal questionnaire. RESULTS: After adjustment for age,
      sex, history of physical workload, recreational physical activity, and previous
      knee injury, weight gain resulting to a shift from normal body mass index (BMI <
      or =25 kg/m(2)) to overweight (BMI >25 kg/m(2)) was associated with a higher
      relative risk of knee OA requiring arthroplasty than persistent overweight from
      20-50 years of age, compared with those with normal relative weight during the
      corresponding age period. The odds ratios (OR) were 3.07 (95% confidence interval
      1.87 to 5.05) for those with normal weight at the age of 20 years and overweight
      at two or three of the ages 30, 40 or 50 years, 3.15 (1.85 to 5.36) for those
      with overweight from the age of 30 years, and 2.37 (1.21 to 4.62) for those with
      overweight from the age of 20 years, respectively. CONCLUSION: In adult life, a
      shift from normal to overweight may carry a higher risk for knee OA requiring
      arthroplasty than does constant overweight.

PMID- 15479893
TI  - Thrombophilic factors are not the leading cause of thrombosis in Behcet's
      disease.
AB  - BACKGROUND: Venous and arterial thromboses occur in patients with Behcet's
      disease and are associated with significant morbidity and mortality. Studies on a
      possible association between the occurrence of thrombosis and thrombophilia in
      patients with this disease have been controversial. OBJECTIVE: To determine the
      prevalence of the most common thrombophilias and dyslipidaemia in patients with
      Behcet's disease with and without thrombosis. METHODS: Blood samples from 107
      patients with Behcet's disease who had or did not have thrombosis were analysed
      for factor V Leiden, prothrombin G20210A polymorphism, methylenetetrahydrofolate
      reductase (MTHFR) C677T polymorphism, factor VIII level, homocysteine and C
      reactive protein concentrations, dyslipidaemia, and plasma glucosylceramide.
      RESULTS: There was no difference between patients with and without thrombosis in
      the prevalence of prothrombin G20210A polymorphism, factor V Leiden, homozygous
      MTHFR C677T, or plasma concentrations of homocysteine, C reactive protein, or
      glucosylceramide. In contrast, patients with thrombosis were found to have
      significantly higher mean levels of factor VIII, total cholesterol,
      triglycerides, VLDL cholesterol, and apolipoproteins B-100, C-II, and C-III than
      those without thrombosis. Multistepwise logistic regression analysis showed that
      triglyceride concentration was the best marker associated with thrombosis (p =
      0.008), with an estimated odds ratio of 1.58 (95% confidence interval, 1.09 to
      2.30) for a difference of 40 mg/dl. CONCLUSIONS: Thrombophilia does not seem to
      play a major role in the tendency to thrombosis in Behcet's disease. However,
      dyslipidaemia, predominantly hypertriglyceridaemia, might be a risk factor.

PMID- 15479894
TI  - The pustular skin lesions in Behcet's syndrome are not sterile.
AB  - BACKGROUND: The pustular skin lesions of Behcet's syndrome (BS) are clinically
      and histopathologically similar to ordinary acne, but BS patients get lesions at
      sites not commonly involved in acne, such as the legs and arms. The microbiology
      of these lesions has not been studied adequately. OBJECTIVE: To make a detailed
      study of the microbiology of BS lesions. METHODS: Subjects were patients with BS
      and acne vulgaris. Material was extracted from pustular lesions and directly
      plated to aerobic and anaerobic media by sterile swab. Anaerobic bacteria were
      identified using a commercial kit (API 20A). Aerobic bacteria were defined by
      standard procedures. RESULTS: 58 BS patients and 37 acne patients were studied.
      Pustules were cultured from the following sites: BS patients (70 pustules): face
      (17), back (30), chest (2), arm (4), leg (17); acne patients (37 pustules): face
      (27), back (6), chest (1), arm (2), leg (1). At least one type of microorganism
      was grown from each pustule. Staphylococcus aureus (41/70, 58.6%, p = 0.008) and
      Prevotella spp (17/70, 24.3%, p = 0.002) were significantly more common in
      pustules from BS patients, and coagulase negative staphylococci (17/37, 45.9%, p
      = 0.007) in pustules from acne patients. CONCLUSIONS: The pustular lesions of BS
      are not usually sterile. The microbiology of these lesions is different from
      ordinary acne. It remains to be determined whether the infection is secondary or
      has any pathogenic implications.

PMID- 15479895
TI  - Effects of RWJ 67657, a p38 mitogen activated protein kinase (MAPK) inhibitor, on
      the production of inflammatory mediators by rheumatoid synovial fibroblasts.
AB  - OBJECTIVE: To investigate the effect of the p38 mitogen activated protein kinase
      (MAPK) inhibitor RWJ 67657 on inflammatory mediator production by rheumatoid
      synovial fibroblasts (RSF). METHODS: RSF were pretreated with RWJ 67657 and
      stimulated with TNF alpha and/or IL-1 beta. Protein levels and mRNA expression of
      MMP-1, MMP-3, TIMP-1, IL-6, and IL-8 were determined, as was mRNA expression of
      COX-2 and ADAMTS-4. RESULTS: MMP-3 production was significantly inhibited at 1
      microM RWJ 67657 and MMP-1 production at 10 microM, while TIMP-1 production was
      not inhibited. Inhibition of IL-6 and IL-8 protein production was seen at 0.1
      microM RWJ 67657. Expression profiles of mRNA were in accordance with protein
      production. Inhibition of COX-2 mRNA expression occurred at 0.01 microM RWJ
      67657. CONCLUSIONS: RWJ 67657 inhibits major proinflammatory mediator production
      in stimulated RSF at pharmacologically relevant concentrations. These findings
      could have important relevance for the treatment of rheumatoid arthritis.

PMID- 15479896
TI  - Short course prednisolone for adhesive capsulitis (frozen shoulder or stiff
      painful shoulder): a randomised, double blind, placebo controlled trial.
AB  - OBJECTIVE: To determine whether a short course of prednisolone is superior to
      placebo for improving pain, function, and range of motion in adhesive capsulitis.
      DESIGN: Double blind, randomised, placebo controlled trial. SETTING: Community
      based rheumatology practice in Australia. PARTICIPANTS: 50 participants (24
      active, 26 placebo); 46 completed the 12 week protocol. Entry criteria were age >
      or =18 years, pain and stiffness in predominantly one shoulder for > or =3 weeks,
      and restriction of passive motion by >30 degrees in two or more planes.
      INTERVENTIONS: 30 mg oral prednisolone/day for three weeks or placebo. MAIN
      OUTCOME MEASURES: Overall, night, and activity related pain, SPADI, Croft
      shoulder disability questionnaire, DASH, HAQ, SF-36, participant rated
      improvement, and range of active motion measured at baseline and at 3, 6, and 12
      weeks. RESULTS: At 3 weeks, there was greater improvement in overall pain in the
      prednisolone group than in the placebo group (mean (SD) change from baseline, 4.1
      (2.3) v 1.4 (2.3); adjusted difference in mean change between the two groups, 2.4
      (95% CI, 1.1 to 3.8)). There was also greater improvement in disability, range of
      active motion, and participant rated improvement (marked or moderate overall
      improvement in 22/23 v 11/23; RR = 2 (1.3 to 3.1), p = 0.001). At 6 weeks the
      analysis favoured the prednisolone group for most outcomes but none of the
      differences was significant. At 12 weeks, the analysis tended to favour the
      placebo group. CONCLUSIONS: A three week course of 30 mg prednisolone daily is of
      significant short term benefit in adhesive capsulitis but benefits are not
      maintained beyond six weeks.

PMID- 15479897
TI  - Anti-CD4 monoclonal antibody treatment in acute and early chronic antigen induced
      arthritis: influence on macrophage activation.
AB  - OBJECTIVE: To investigate the indirect effects of anti-CD4 treatment on the
      functions of macrophages (CD4(-) in mice) in the acute and early chronic phase of
      mouse antigen induced arthritis (AIA). METHODS: C57BL/6 mice with AIA were
      treated intraperitoneally with the anti-CD4 mAb GK1.5 or control rat IgG on days 
      1, 0, 1, 3, 5, and 7. Proinflammatory cytokines (IL1 beta, IL6, and TNF alpha)
      were quantified by sandwich ELISA in joint extracts, serum, and supernatants of
      ex vivo stimulated spleen/lymph node cells or peritoneal macrophages (+LPS/IFN
      gamma). Nitric oxide (NO) levels in supernatants of ex vivo stimulated peritoneal
      macrophages were measured by the Griess reaction. Proteolytic activity in joint
      homogenates was analysed by gelatin, casein, and elastin zymography, and
      substrate assays. RESULTS: Anti-CD4 treatment significantly reduced joint
      swelling in acute (days 3, 5) and early chronic AIA (day 7) and diminished
      inflammation and destruction scores in late chronic AIA (day 21). On day 3, anti
      CD4 treatment significantly reduced IL6 levels in all compartments. IL1 beta was
      reduced in joint extracts, unaffected in serum or cells from lymphoid organs, and
      increased in stimulated peritoneal macrophages. TNF alpha was significantly
      increased in the joints, decreased in serum, and otherwise unchanged. NO
      production by stimulated peritoneal macrophages was significantly reduced by anti
      CD4 treatment. Lower activity of matrix metalloproteinases and neutrophil
      elastase was seen in joint extracts of anti-CD4 treated animals than in IgG
      treated AIA controls. CONCLUSION: CD4(+) T cell directed treatment had strong
      local and systemic effects on macrophages. These indirect effects may contribute
      to the reduction of destructive mediators/joint destruction in AIA.

PMID- 15479898
TI  - High avidity anti-beta 2-glycoprotein I antibodies in patients with
      antiphospholipid syndrome.
AB  - OBJECTIVE: To evaluate avidity of IgG anti-beta 2-glycoprotein I antibodies (anti
      beta2-GPI) in patients with antiphospholipid syndrome (APS) and systemic lupus
      erythematosus (SLE) in relation to thrombosis, and to demonstrate a possible
      affinity maturation of IgG anti-beta 2-GPI during the disease course. METHODS: 64
      sera from 32 patients (18 with primary or secondary APS, 14 with SLE without APS)
      and their respective IgG fractions or affinity purified anti-beta 2-GPI were
      studied by anticardiolipin (aCL) and anti-beta 2-GPI enzyme linked immunosorbent
      assay and by chaotropic assay. RESULTS: Six, 12, and 14 patients had high, low,
      and heterogeneous avidity IgG anti-beta 2-GPI, respectively. In 12 patients an
      increase in antibody avidity was observed over a period of between four and 12
      years. More patients with APS were in the high avidity than in the low avidity
      anti-beta 2-GPI group, while the opposite was observed for SLE alone (both
      p<0.05). The most common clinical feature among patients with high avidity anti
      beta 2-GPI was thrombosis, mainly venous thrombosis (p<0.05 and p<0.02,
      respectively, v the low avidity anti-beta 2-GPI group). CONCLUSIONS: Patients
      with APS with or without SLE may have anti-beta2-GPI of high, low, or
      heterogeneous avidity. High avidity anti-beta 2-GPI appear to be associated with
      thrombosis and APS, while in pure SLE low avidity anti-beta 2-GPI may prevail.
      Monitoring of avidity may help elucidate the role of anti-beta 2-GPI affinity
      maturation in the pathogenesis of APS.

PMID- 15479899
TI  - Inequalities in access to knee joint replacements for people in need.
AB  - OBJECTIVES: To quantify the effects of socioeconomic deprivation and rurality on
      evidence of need for total knee joint replacement and the use of health services,
      after adjusting for age and sex. METHODS: A random stratified sample of 15 000
      people aged > or =65 years taken from central age/sex registers for the
      geographical areas covered by the previous Sheffield and Wiltshire Health
      Authorities. A self completion validated questionnaire was then mailed directly
      to subjects to assess need for knee joint replacement surgery and whether general
      practice and hospital services were being used. Subjects were followed up for 18
      months to evaluate access to surgery. RESULTS: The response rate was 78% after
      three mailings. In those aged 65 years and over (with and without comorbidity),
      the proportion with no comorbid factors and in need of knee replacement was 5.1%;
      the rate of need among subjects without comorbidity was 7.9%. There were
      inequalities in health and access to health related to age, sex, geography, and
      deprivation but not rurality. People who were more deprived had greater need.
      Older and deprived people were less likely to access health services. Only 6.4%
      of eligible people received knee replacement surgery after 18 months of follow
      up. CONCLUSIONS: There is an important unmet need in older people, with
      significant age, sex, geographical, and deprivation inequalities in levels of
      need and access to services. The use of waiting list numbers as a performance
      indicator is perverse for this procedure. There is urgent need to expand
      orthopaedic services and training.

PMID- 15479900
TI  - Correlation and sex differences between ankle and knee cartilage morphology
      determined by quantitative magnetic resonance imaging.
AB  - OBJECTIVE: To study the correlation between ankle and knee cartilage morphology
      to test the hypothesis that knee joint cartilage loss in gonarthritis can be
      estimated retrospectively using quantitative MRI analysis of the knee and ankle
      and established regression equations; and to test the hypothesis that sex
      differences in joint surface area are larger in the knee than the ankle, which
      may explain the greater incidence of knee osteoarthritis in elderly women than in
      elderly men. METHODS: Sagittal MR images (3D FLASH WE) of the knee and hind foot
      were acquired in 29 healthy subjects (14 women, 15 men; mean (SD) age, 25 (3)
      years), with no signs joint disease. Cartilage volume, thickness, and joint
      surface area were determined in the knee, ankle, and subtalar joint. RESULTS:
      Knee cartilage volumes and joint surface areas showed only moderate correlations
      with those of the ankle and subtalar joint (r = 0.33 to 0.81). The correlations
      of cartilage thickness between the two joints were weaker still (r = -0.05 to
      0.53). Sex differences in cartilage morphology at the knee and the ankle were
      similar, with surface areas being -17.5% to -23.5% lower in women than in men.
      CONCLUSIONS: Only moderate correlations in cartilage morphology of healthy
      subjects were found between knee and ankle. It is therefore impractical to
      estimate knee joint cartilage loss a posteriori in cross sectional studies by
      measuring the hind foot and then applying a scaling factor. Sex differences in
      cartilage morphology do not explain differences in osteoarthritis incidence
      between men and women in the knee and ankle.

PMID- 15479901
TI  - Late neonatal lupus erythematosus onset in a child born of a mother with primary
      Sjogren's syndrome.
AB  - BACKGROUND: The neonatal lupus syndrome can be present as congenital heart block
      (CHB) or as neonatal lupus erythematosus (NLE), both seldom passively acquired
      autoimmune diseases. CHB starts around week 20 of pregnancy and is a lifelong
      event, whereas NLE is self limiting and usually starts at the 6th week of the
      child's age-the maximum recorded up to week 20. CASE REPORT: An asymptomatic
      mother with primary Sjogren's syndrome and anti-SSA/Ro52, anti-SSA/Ro60, and anti
      SSB/La autoantibodies is described who, at gestational week 23 during her first
      pregnancy, was diagnosed as having a male fetus with CHB due to third degree
      atrioventricular block. The boy from the second pregnancy developed skin
      eruptions which clinically and by biopsy were compatible with NLE at week 20+1
      post partum. CONCLUSIONS: Our case of NLE, starting at week 20+1 of age, seems to
      be the latest reported clinical case of NLE. Development of CHB and NLE in two
      consecutive boy pregnancies is unusual.

PMID- 15479902
TI  - Seasonal variation of disease activity of systemic lupus erythematosus in
      Finland: a 1 year follow up study.
AB  - OBJECTIVES: To study the role of different seasons in the disease activity of
      patients with systemic lupus erythematosus (SLE). Additionally, to evaluate
      whether the outdoor behaviour during the summer or a photoprovocation test
      affects disease activity. METHODS: 33 patients with SLE were examined by a
      rheumatologist and a dermatologist at a university hospital in winter, spring,
      and summer. The activity of SLE was assessed by the ECLAM index. Their outdoor
      behaviour was recorded by a questionnaire during the summer. In the winter, 12
      patients were photoprovoked by ultraviolet A and B radiation on a small skin
      area. RESULTS: The ECLAM scores were higher in spring and tended to be higher in
      summer than in winter (p = 0.006 and p = 0.051). This finding, as well as the
      outdoor behaviour, were independent of the patients' own impression of their
      photosensitivity. Overall, the sun protection actions were inadequate. The
      photoprovocation had no statistical effect on disease activity, but one patient
      had a violent exacerbation of SLE manifestations shortly after the
      photoprovocation. CONCLUSIONS: In the northern climate SLE may be activated
      during the sunny season. Therefore, more effort should be focused on sun
      protection of patients with SLE.

PMID- 15479903
TI  - Gluten sensitivity masquerading as systemic lupus erythematosus.
AB  - CASE REPORTS: Three patients are described whose original presentation and
      immunological profile led to the erroneous diagnosis of systemic lupus
      erythematosus. The correct diagnosis of gluten sensitivity was made after years
      of treatment with steroids and other immunosuppressive drugs. CONCLUSIONS: The
      immunological profile of IgA deficiency and/or raised double stranded DNA in the
      absence of antinuclear factor together with raised inflammatory markers and
      symptoms suggestive of an immune diathesis should alert the physician to the
      possibility of gluten sensitivity. The presence of an enteropathy is no longer a
      prerequisite for the diagnosis of gluten sensitivity, which can solely present
      with extraintestinal symptoms and signs. Knowledge of the diverse manifestations
      of gluten sensitivity is essential in avoiding such misdiagnosis.

PMID- 15479904
TI  - Hypothalamic-pituitary-gonadal axis and cortisol in young women with primary
      fibromyalgia: the potential roles of depression, fatigue, and sleep disturbance
      in the occurrence of hypocortisolism.
AB  - OBJECTIVES: To investigate abnormalities of the hypothalamic-pituitary-gonadal
      (HPG) axis and cortisol concentrations in young women with primary fibromyalgia
      (FM); and to determine whether depression, fatigue, and sleep disturbance affect
      these hormones. METHODS: Follicle stimulating hormone (FSH), luteinising hormone
      (LH), oestradiol, progesterone, prolactin, and cortisol concentrations in 63
      women with FM were compared with those in 38 matched healthy controls; all
      subjects aged <35 years. The depression rate was assessed by the Beck Depression
      Inventory (BDI) and patients with high and low BDI scores were compared.
      Additionally, patients were divided according to sleep disturbance and fatigue
      and compared both with healthy controls and within the group. RESULTS: No
      significant differences in FSH, LH, oestradiol, prolactin, and progesterone
      levels were found between patients with FM and controls, but cortisol levels were
      significantly lower in patients than in controls (p<0.05). Cortisol levels in
      patients with high BDI scores, fatigue, and sleep disturbance were significantly
      lower than in controls (p<0.05). Correlation between cortisol levels and number
      of tender points in all patients was significant (r = -0.32, p<0.05). CONCLUSION:
      Despite low cortisol concentrations in young women with FM, there is no
      abnormality in HPG axis hormones. Because fatigue, depression rate, sleep
      disturbance, and mean age of patients affect cortisol levels, these variables
      should be taken into account in future investigations.

PMID- 15479905
TI  - Diagnosis and follow up of aortitis in the elderly.
AB  - OBJECTIVES: To evaluate the correlation of MRI and [(18)F]FDG-PET scans with the
      clinical course and inflammatory markers in patients with aortitis. METHODS:
      Eight patients with aortitis presenting with unspecific GCA-like symptoms were
      examined. Aortitis was diagnosed and followed up by [(18)F]FDG-PET and MRI. The
      aorta was divided into three vascular regions (ascending aorta, aortic arch, and
      descending aorta) to localise the aortic inflammation and compare both imaging
      techniques. RESULTS: were correlated with clinical and laboratory examinations.
      RESULTS: At diagnosis, 20/24 vascular regions from eight patients were positive
      by [(18)F]FDG-PET scan and 15/21 aortic regions by MRI. Patients were treated
      with corticosteroids and followed up for a mean (SD) of 13.3 (4.7) months. In
      [(18)F]FDG-PET, 11/20 (55%) initially pathological aortic regions returned to
      normal in the follow up examination, which correlated closely with the clinical
      and laboratory follow up examination. Conversely, in MRI, 14/15 initially
      affected vascular regions were unchanged. CONCLUSIONS: [(18)F]FDG-PET and MRI are
      both effective techniques for detecting early aortitis and have a high
      correlation with laboratory inflammatory measures. However, during the follow up
      examination, [(18)F]FDG-PET uptake decreased in line with the clinical symptoms
      and inflammatory serum markers, whereas MRI scans gave more static results.

PMID- 15479906
TI  - Sera from children with active Henoch-Schonlein purpura can enhance the
      production of interleukin 8 by human umbilical venous endothelial cells.
AB  - OBJECTIVE: To investigate the ability of sera from children with active Henoch
      Schonlein purpura (HSP) to enhance endothelial interleukin (IL) 8 production and
      intercellular adhesion molecule (ICAM)-1 expression. METHODS: Nine children with
      active HSP and nine normal healthy children were enrolled. IL8 serum levels of
      patients and controls at different stages were analysed. Production of IL8 and
      expression of ICAM-1 by human umbilical venous endothelial cells were detected
      (ELISA for IL8, flow cytometry for ICAM-1) and compared under various stimuli,
      including sera of patients at different stages, sera of controls, and medium
      alone. RESULTS: Serum levels of IL8 were increased at the acute stage. Levels of
      IL8 in supernatants from human umbilical venous endothelial cells (HUVEC) co
      cultured with sera from children with active HSP were significantly higher than
      those from HUVEC without any treatment (p = 0.001), HUVEC treated with inactive
      sera (p = 0.004), and HUVEC treated with sera from healthy controls (p = 0.004).
      Sera from patients and from controls did not enhance the expression of ICAM-1 on
      HUVEC. CONCLUSIONS: Some factors may be present in sera from children with active
      HSP that could activate endothelial cells to produce IL8. This process may
      account, in part, for the mechanisms of perivascular neutrophil infiltration and
      leucocytosis in HSP.

PMID- 15479907
TI  - Autoantibodies against phosphatidylserine-prothrombin complex in patients with
      systemic sclerosis.
AB  - OBJECTIVE: To determine the frequency and clinical association of
      antiphosphatidylserine-prothrombin complex (PS/PT) antibody (Ab) in systemic
      sclerosis (SSc). METHODS: Anti-PS/PT IgG Ab was examined by enzyme linked
      immunosorbent assay (ELISA) in 112 patients with SSc. Thirty three healthy
      volunteers and 30 patients with systemic lupus erythematosus (SLE) were also
      investigated as controls. RESULTS: Anti-PS/PT Ab was detected in 18/112 (16%)
      patients with SSc and 10/30 (33%) patients with SLE, whereas it was not detected
      in any normal controls. Anti-PS/PT Ab was more frequently detected in patients
      with SSc with peripheral ischaemia and lung disease (pulmonary fibrosis and
      pulmonary hypertension) than in patients with SSc without the Ab. However, anti
      PS/PT Ab was not associated with the severity of skin sclerosis. Importantly, two
      patients were negative for both lupus anticoagulant and Ab against cardiolipin
      beta(2)-glycoprotein I complex among six anti-PS/PT Ab positive patients with SSc
      and a thromboembolic episode. CONCLUSIONS: Anti-PS/PT Ab is associated with
      thromboembolism, peripheral ischaemia, and lung involvement in some patients with
      SSc. Examination of this Ab may be useful to recognise the risk of
      thromboembolism in patients with SSc.

PMID- 15479908
TI  - Small vessel vasculitis and relapsing panniculitis in tumour necrosis factor
      receptor associated periodic syndrome (TRAPS).
AB  - CASE REPORTS: A 66 year old female patient had relapsing fever and non
      suppurative panniculitis suggestive of enigmatic "Weber-Christian disease" (WCD).
      Antineutrophil cytoplasmic antibodies with specificity for human leucocyte
      elastase (HLE-ANCA) were detected. A biopsy showed small vessel vasculitis and
      panniculitis. A 53 year old man had recurrent episodes of abdominal pain,
      erythematous rash, and myalgia. Fever attacks had stopped a few years ago. A
      biopsy showed panniculitis and fasciitis. In both patients mutations (R92Q, T50M)
      of the tumour necrosis factor receptor super family (TNFRSF) 1A gene were
      disclosed. Mutations of the TNFRSF 1A gene are the cause of tumour necrosis
      factor receptor associated periodic syndrome (TRAPS). Both patients responded
      favourably to treatment with the human soluble p75 TNF alpha receptor fusion
      protein etanercept (2 x 25 mg subcutaneously/week). DISCUSSION: Small vessel
      vasculitis and panniculitis have not been reported in TRAPS so far. The cases
      underline the importance of TNF alpha regulation in inflammatory processes
      including vasculitis. Genetically determined causes of fever may account for some
      cases of WCD.

PMID- 15479909
TI  - Extended colonic ulcerations in a patient with microscopic polyangiitis.

PMID- 15479910
TI  - Severe digital ischaemia treated with phosphodiesterase inhibitors.

PMID- 15479911
TI  - Hereditary C1q deficiency and secondary Sjogren's syndrome.

PMID- 15479912
TI  - Acute pneumonitis starting 2 hours after intramuscular gold administration in a
      patient with rheumatoid arthritis.

PMID- 15479913
TI  - An unusual complication of appendicitis.

PMID- 15479914
TI  - Interferon alfa in protracted arthritis of familial Mediterranean fever: a robust
      alternative for synovectomy.

PMID- 15479915
TI  - Transient bone marrow oedema in a child.

PMID- 15479916
TI  - Joint lavage and pseudogout.

PMID- 15479917
TI  - Long term treatment of psoriatic arthritis with infliximab.

PMID- 15479918
TI  - Immunohistochemistry of normal synovium.

PMID- 15479919
TI  - Low dose prednisolone for treatment of RA.

PMID- 15479921
TI  - Health officials brace for flu season.

PMID- 15479922
TI  - Government drafts flu preparedness plan: concerns about serious pandemic spur
      effort.

PMID- 15479926
TI  - Intrathecal ziconotide for chronic pain.

PMID- 15479927
TI  - Notice of duplicate publication.

PMID- 15479928
TI  - Handwashing promotion and childhood diarrhea in Pakistan.

PMID- 15479929
TI  - Estrogen receptor alpha polymorphisms and the risk of myocardial infarction.

PMID- 15479930
TI  - Ethics of surrogate consent for living organ donation.

PMID- 15479931
TI  - Nephron-sparing surgery and renal cell carcinoma.

PMID- 15479932
TI  - Premutation alleles associated with Parkinson disease and essential tremor.

PMID- 15479933
TI  - Trends in length of stay, living setting, functional outcome, and mortality
      following medical rehabilitation.
AB  - CONTEXT: Changes in reimbursement have reduced length of stay (LOS) for patients
      receiving inpatient medical rehabilitation. The impact of decreased LOS on
      functional status, living setting, and mortality is not known. OBJECTIVE: To
      examine changes in LOS, functional status, living setting, and mortality in
      patients completing inpatient rehabilitation. DESIGN: Retrospective cohort study
      from 1994 through 2001 using information submitted to the Uniform Data System for
      Medical Rehabilitation. SETTING AND PARTICIPANTS: Data were analyzed from 744
      inpatient medical rehabilitation hospitals and centers located in 48 US states. A
      total of 148,807 patient records from 5 impairment groups (stroke, brain
      dysfunction, spinal cord dysfunction, other neurologic conditions, and orthopedic
      conditions) were examined. Patients' mean age was 67.8 (SD, 15.8) years; the
      sample was 59% female and 81% non-Hispanic white. MAIN OUTCOME MEASURES:
      Discharge setting, follow-up living setting, change in functional status, and
      mortality. RESULTS: Median LOS decreased from 20 to 12 days (P<.001) from 1994 to
      2001. The proportional decrease in median LOS was greatest (42%) for patients
      with orthopedic conditions. Mean days to follow-up remained constant from 89 in
      1994 to 90 in 2001. Functional status was clinically stable, while efficiency
      (functional status change divided by LOS) increased significantly (P<.001). Rates
      of discharge to home and living at home at follow-up remained stable, ranging
      from 81% to 93%. However, mortality at 80- to 180-day follow-up increased from
      less than 1% in 1994 to 4.7% in 2001. CONCLUSIONS: Length of stay for inpatient
      rehabilitation decreased substantially from 1994 to 2001. Effectiveness as
      measured by change in functional status did not change clinically, and living
      setting did not change. Efficiency for functional outcomes improved but mortality
      at follow-up increased.

PMID- 15479934
TI  - Vaccine policy changes and epidemiology of poliomyelitis in the United States.
AB  - CONTEXT: The last case of poliomyelitis in the United States due to indigenously
      acquired wild poliovirus occurred in 1979; however, as a consequence of oral
      poliovirus vaccine (OPV) use that began in 1961, an average of 9 cases of vaccine
      associated paralytic poliomyelitis (VAPP) were confirmed each year from 1961
      through 1989. To reduce the VAPP burden, national vaccination policy changed in
      1997 from reliance on OPV to options for a sequential schedule of inactivated
      poliovirus vaccine (IPV) followed by OPV. In 2000, an exclusive IPV schedule was
      adopted. OBJECTIVE: To review the epidemiology of paralytic poliomyelitis and
      document the association between the vaccine schedule changes and VAPP in the
      United States. DESIGN AND SETTING: Review of national surveillance data from 1990
      through 2003 for cases of confirmed paralytic poliomyelitis. MAIN OUTCOME
      MEASURES: Number of confirmed paralytic poliomyelitis cases, including VAPP, and
      ratio of VAPP cases to number of doses of OPV distributed that occurred before,
      during, and after implementation of policy changes. RESULTS: From 1990 through
      1999, 61 cases of paralytic poliomyelitis were reported; 59 (97%) of these were
      VAPP (1 case per 2.9 million OPV doses distributed), 1 case was imported, and 1
      case was indeterminate. Thirteen cases occurred during the 1997-1999 transitional
      policy period and were associated with the all-OPV schedule; none occurred with
      the IPV-OPV schedule. No cases occurred after the United States implemented the
      all-IPV policy in 2000. The last imported poliomyelitis case occurred in 1993 and
      the last case of VAPP occurred in 1999. CONCLUSION: The change in polio
      vaccination policy from OPV to exclusive use of IPV was successfully implemented;
      this change led to the elimination of VAPP in the United States.

PMID- 15479935
TI  - Postlicensure safety surveillance for 7-valent pneumococcal conjugate vaccine.
AB  - CONTEXT: Clinical trials evaluate a vaccine's safety before approval, but some
      risks may escape detection or adequate characterization until larger population
      exposures occur after licensure. OBJECTIVE: To summarize reports of events
      occurring after vaccination with 7-valent pneumococcal conjugate vaccine (PCV),
      including those that may warrant further investigation to assess possible
      causation by PCV. DESIGN: Descriptive epidemiology of reports submitted to the
      Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance
      database. SETTING AND PATIENTS: United States during first 2 years after
      licensure of PCV (February 2000 through February 2002). Reports studied were for
      children younger than 18 years and vaccinated with PCV. MAIN OUTCOME MEASURES:
      Numbers and proportional distributions of reports. RESULTS: A total of 4154
      reports of events following PCV were submitted to VAERS, for a rate of 13.2
      reports per 100,000 doses distributed. Multiple vaccines were given in 74.3% of
      reports. The most frequently reported symptoms and signs included fever,
      injection site reactions, fussiness, rashes, and urticaria. Serious events were
      described in 14.6% of reports. There were 117 deaths, 23 reports of positive
      rechallenges, and 34 cases of invasive pneumococcal infections possibly
      representing vaccine failure. Immune-mediated events occurred in 31.3% of
      reports. All 14 patients with anaphylactic or anaphylactoid reactions survived.
      Thrombocytopenia developed in 14 patients and serum sickness in 6 others.
      Neurologic symptoms occurred in 38% of reports. Seizures described in 393 reports
      included 94 febrile seizures. CONCLUSIONS: The majority of reports to VAERS in
      the first 2 years after licensure of PCV described generally minor adverse events
      previously identified in clinical trials. The proportion of reports portraying
      serious events was similar to that for other vaccines. Although there are
      important limitations in passive surveillance data, and caution in their
      interpretation is necessary, symptoms experienced by a few children more than
      once after successive PCV doses, including allergic reactions, prolonged or
      abnormal crying, fussiness, dyspnea, and gastrointestinal distress, warrant
      continued surveillance, as do reports of rare but potentially serious events,
      such as seizures, anaphylactic or anaphylactoid reactions, serum sickness, and
      thrombocytopenia.

PMID- 15479936
TI  - Influence of patient literacy on the effectiveness of a primary care-based
      diabetes disease management program.
AB  - CONTEXT: Low literacy is an important barrier for patients with diabetes, but
      interventions to address low literacy have not been well examined. OBJECTIVE: To
      examine the role of literacy on the effectiveness of a comprehensive disease
      management program for patients with diabetes. DESIGN, SETTING, AND PARTICIPANTS:
      Analysis of the influence of literacy on glycemic control and systolic blood
      pressure using data from a randomized controlled trial (conducted from February
      2001 through April 2003) of a comprehensive diabetes management program.
      Participants were 217 patients aged 18 years or older with type 2 diabetes and
      poor glycemic control (glycosylated hemoglobin [HbA1c] levels > or =8.0%) and
      presenting to a US academic general internal medicine practice. INTERVENTIONS:
      All communication to patients was individualized and delivered to enhance
      comprehension among patients with low literacy. Intervention patients received
      intensive disease management from a multidisciplinary team. Control patients
      received an initial management session and continued with usual care. MAIN
      OUTCOME MEASURES: Achievement of goal HbA1c levels and systolic blood pressure at
      12-month follow-up for control and intervention patients stratified by literacy
      status. RESULTS: Complete 12-month data were available for 193 patients (89%).
      Among patients with low literacy, intervention patients were more likely than
      control patients to achieve goal HbA1c levels (< or =7.0%) (42% vs 15%,
      respectively; adjusted odds ratio [OR], 4.6; 95% confidence interval [CI], 1.3 to
      17.2; P = .02). Patients with higher literacy had similar odds of achieving goal
      HbA1c levels regardless of intervention status (24% vs 23%; adjusted OR, 1.0; 95%
      CI, 0.4 to 2.5; P = .98). Improvements in systolic blood pressure were similar by
      literacy status. CONCLUSIONS: Literacy may be an important factor for predicting
      who will benefit from an intervention for diabetes management. A diabetes disease
      management program that addresses literacy may be particularly beneficial for
      patients with low literacy, and increasing access to such a program could help
      reduce health disparities.

PMID- 15479937
TI  - Regionalization of percutaneous transluminal coronary angioplasty and
      implications for patient travel distance.
AB  - CONTEXT: Minimum procedure volume thresholds have been proposed to improve
      outcomes among patients undergoing percutaneous transluminal coronary angioplasty
      (PTCA). How regionalization policies would affect patient travel distances is not
      known. OBJECTIVE: To examine the effect of regionalization of PTCA on patient
      travel distances. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study
      of discharge records, which were examined to determine hospital and operator
      procedure volumes, of 97,401 patients undergoing PTCA in New York, New Jersey,
      and Florida in 2001. Travel distances were measured at baseline and under 2
      regionalization scenarios in which hospital-operator pairs not meeting minimum
      volume standards stopped providing services. MAIN OUTCOME MEASURES: Observed and
      expected patient travel distances, and risk-adjusted mortality. RESULTS: With a
      minimum volume standard of 175 per operator and 400 per hospital (class 1), 25%
      of patients had a shorter travel distance, 10% had a longer travel distance, and
      65% experienced no change. Most patients with longer travel distances under this
      standard would travel no more than 25 miles farther, and most patients with
      shorter travel distances would save no more than 10 miles. With a minimum volume
      standard of 75 per operator and 400 per hospital (class 2), 11% of patients had a
      shorter travel distance, 2% had a longer travel distance, and 87% experienced no
      change. Under both standards, less than 1% of patients would travel more than 50
      miles farther than their observed travel distance. Risk-adjusted mortality was
      higher for lower-volume hospital-operator pairs (1.2% for class 3 vs 0.9% for
      class 2 and 0.8% for class 1; P<.001 for both comparisons). CONCLUSION:
      Regionalization of PTCA would not increase travel distance for most patients;
      however, potential costs of regionalization not related to travel must be
      examined before such policies can be recommended.

PMID- 15479938
TI  - Bariatric surgery: a systematic review and meta-analysis.
AB  - CONTEXT: About 5% of the US population is morbidly obese. This disease remains
      largely refractory to diet and drug therapy, but generally responds well to
      bariatric surgery. OBJECTIVE: To determine the impact of bariatric surgery on
      weight loss, operative mortality outcome, and 4 obesity comorbidities (diabetes,
      hyperlipidemia, hypertension, and obstructive sleep apnea). DATA SOURCES AND
      STUDY SELECTION: Electronic literature search of MEDLINE, Current Contents, and
      the Cochrane Library databases plus manual reference checks of all articles on
      bariatric surgery published in the English language between 1990 and 2003. Two
      levels of screening were used on 2738 citations. DATA EXTRACTION: A total of 136
      fully extracted studies, which included 91 overlapping patient populations (kin
      studies), were included for a total of 22,094 patients. Nineteen percent of the
      patients were men and 72.6% were women, with a mean age of 39 years (range, 16-64
      years). Sex was not reported for 1537 patients (8%). The baseline mean body mass
      index for 16 944 patients was 46.9 (range, 32.3-68.8). DATA SYNTHESIS: A random
      effects model was used in the meta-analysis. The mean (95% confidence interval)
      percentage of excess weight loss was 61.2% (58.1%-64.4%) for all patients; 47.5%
      (40.7%-54.2%) for patients who underwent gastric banding; 61.6% (56.7%-66.5%),
      gastric bypass; 68.2% (61.5%-74.8%), gastroplasty; and 70.1% (66.3%-73.9%),
      biliopancreatic diversion or duodenal switch. Operative mortality (< or =30 days)
      in the extracted studies was 0.1% for the purely restrictive procedures, 0.5% for
      gastric bypass, and 1.1% for biliopancreatic diversion or duodenal switch.
      Diabetes was completely resolved in 76.8% of patients and resolved or improved in
      86.0%. Hyperlipidemia improved in 70% or more of patients. Hypertension was
      resolved in 61.7% of patients and resolved or improved in 78.5%. Obstructive
      sleep apnea was resolved in 85.7% of patients and was resolved or improved in
      83.6% of patients. CONCLUSIONS: Effective weight loss was achieved in morbidly
      obese patients after undergoing bariatric surgery. A substantial majority of
      patients with diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea
      experienced complete resolution or improvement.

PMID- 15479939
TI  - Decision making at a time of crisis near the end of life.
AB  - As patients approach the end of life, their disease process may create an
      immediate life-threatening emergency, yet invasive interventions may be less
      likely to provide benefit while carrying the same or greater risks. Knowing when
      it is time to shift from life-prolonging to more palliative approaches, focused
      on quality of life and comfort, is emotionally and clinically challenging for
      patients, families, and physicians. Key factors in the decision process include
      prognosis, risk-benefit analysis of the proposed intervention, current symptom
      burden, temporal pattern of the illness, patient's age and life stage, and the
      patient's goals of care. A structured approach to decision making includes
      assessing the patient's physical, psychological, and spiritual needs; assessing
      the patient's support system; discussing prognosis; and assessing patient
      specific goals. Physicians can best help patients decide which treatments are
      appropriate by taking the necessary time to explore all curative and palliative
      care options, providing honest and timely prognostic information, making clear
      recommendations, facilitating patient-family discussions, and affirming patient
      choices.

PMID- 15479940
TI  - Palliative care for patients with heart failure.

PMID- 15479941
TI  - Duplicate publication, multiple problems.

PMID- 15479942
TI  - Inpatient rehabilitation outcome trends: implications for the future.

PMID- 15479943
TI  - Poliomyelitis in the United States: the final chapter?

PMID- 15479944
TI  - JAMA patient page. Polio.

PMID- 15479945
TI  - An intermediate grade of finished genomic sequence suitable for comparative
      analyses.
AB  - Although the cost of generating draft-quality genomic sequence continues to
      decline, refining that sequence by the process of "sequence finishing" remains
      expensive. Near-perfect finished sequence is an appropriate goal for the human
      genome and a small set of reference genomes; however, such a high-quality product
      cannot be cost-justified for large numbers of additional genomes, at least for
      the foreseeable future. Here we describe the generation and quality of an
      intermediate grade of finished genomic sequence (termed comparative-grade
      finished sequence), which is tailored for use in multispecies sequence
      comparisons. Our analyses indicate that this sequence is very high quality (with
      the residual gaps and errors mostly falling within repetitive elements) and
      reflects 99% of the total sequence. Importantly, comparative-grade sequence
      finishing requires approximately 40-fold less reagents and approximately 10-fold
      less personnel effort compared to the generation of near-perfect finished
      sequence, such as that produced for the human genome. Although applied here to
      finishing sequence derived from individual bacterial artificial chromosome (BAC)
      clones, one could envision establishing routines for refining sequences emanating
      from whole-genome shotgun sequencing projects to a similar quality level. Our
      experience to date demonstrates that comparative-grade sequence finishing
      represents a practical and affordable option for sequence refinement en route to
      comparative analyses.

PMID- 15479946
TI  - Gene prediction and verification in a compact genome with numerous small introns.
AB  - The genomes of clusters of related eukaryotes are now being sequenced at an
      increasing rate, creating a need for accurate, low-cost annotation of exon-intron
      structures. In this paper, we demonstrate that reverse transcription-polymerase
      chain reaction (RT-PCR) and direct sequencing based on predicted gene structures
      satisfy this need, at least for single-celled eukaryotes. The TWINSCAN gene
      prediction algorithm was adapted for the fungal pathogen Cryptococcus neoformans
      by using a precise model of intron lengths in combination with ungapped
      alignments between the genome sequences of the two closely related Cryptococcus
      varieties. This approach resulted in approximately 60% of known genes being
      predicted exactly right at every coding base and splice site. When previously
      unannotated TWINSCAN predictions were tested by RT-PCR and direct sequencing, 75%
      of targets spanning two predicted introns were amplified and produced high
      quality sequence. When targets spanning the complete predicted open reading frame
      were tested, 72% of them amplified and produced high-quality sequence. We
      conclude that sequencing a small number of expressed sequence tags (ESTs) to
      provide training data, running TWINSCAN on an entire genome, and then performing
      RT-PCR and direct sequencing on all of its predictions would be a cost-effective
      method for obtaining an experimentally verified genome annotation.

PMID- 15479947
TI  - Codon usage bias from tRNA's point of view: redundancy, specialization, and
      efficient decoding for translation optimization.
AB  - The selection-mutation-drift theory of codon usage plays a major role in the
      theory of molecular evolution by explaining the co-evolution of codon usage bias
      and tRNA content in the framework of translation optimization. Because most
      studies have focused only on codon usage, we analyzed the tRNA gene pool of 102
      bacterial species. We show that as minimal generation times get shorter, the
      genomes contain more tRNA genes, but fewer anticodon species. Surprisingly,
      despite the wide G+C variation of bacterial genomes these anticodons are the same
      in most genomes. This suggests an optimization of the translation machinery to
      use a small subset of optimal codons and anticodons in fast-growing bacteria and
      in highly expressed genes. As a result, the overrepresented codons in highly
      expressed genes tend to be the same in very different genomes to match the same
      most-frequent anticodons. This is particularly important in fast-growing
      bacteria, which have higher codon usage bias in these genes. Three models were
      tested to understand the choice of codons recognized by the same anticodons, all
      providing significant fit, but under different classes of genes and genomes.
      Thus, co-evolution of tRNA gene composition and codon usage bias in genomes seen
      from tRNA's point of view agrees with the selection-mutation-drift theory.
      However, it suggests a much more universal trend in the evolution of anticodon
      and codon choice than previously thought. It also provides new evidence that a
      selective force for the optimization of the translation machinery is the
      maximization of growth.

PMID- 15479948
TI  - An active murine transposon family pair: retrotransposition of "master" MusD
      copies and ETn trans-mobilization.
AB  - The ETn (Early Transposon) elements are among the most active murine mobile
      sequences, being responsible for a series of mutations by insertion in vivo. Yet
      they are noncoding, and it had long been suspected that ETn are mobilized in
      trans by coding-competent elements, most probably from the closely related MusD
      family of LTR-retrotransposons. A genome-wide in silico search for coding
      competent MusD elements identified a total of nine such copies, which we cloned
      and marked to test their transpositional activity, using an ex vivo assay in
      heterologous cells. Three copies were found to be autonomous for transposition,
      with each gag, pro, and pol MusD gene absolutely required for mobility. These
      active MusD copies specifically trigger retrotransposition of marked ETn elements
      with high efficiency, by complementation in trans. Characterization of the
      structures of de novo transposed MusD and ETn marked elements, as well as of
      their integration sites, disclosed canonical retroviral-like retrotransposition,
      with 6-bp target site duplications common to both elements. These results
      highlight the parasitic molecular strategies that are used by the ETn elements
      for their mobility, and unambiguously identify their "master genes."

PMID- 15479949
TI  - Psi-Phi: exploring the outer limits of bacterial pseudogenes.
AB  - Because bacterial chromosomes are tightly packed with genes and were
      traditionally viewed as being optimized for size and replication speed, it was
      not surprising that the early annotations of sequenced bacterial genomes reported
      few, if any, pseudogenes. But because pseudogenes are generally recognized by
      comparisons with their functional counterparts, as more genome sequences
      accumulated, many bacterial pathogens were found to harbor large numbers of
      truncated, inactivated, and degraded genes. Because the mutational events that
      inactivate genes occur continuously in all genomes, we investigated whether the
      rarity of pseudogenes in some bacteria was attributable to properties inherent to
      the organism or to the failure to recognize pseudogenes. By developing a program
      suite (called Psi-Phi, for Psi-gene Finder) that applies a comparative method to
      identify pseudogenes (attributable both to misannotation and to nonrecognition),
      we analyzed the pseudogene inventories in the sequenced members of the
      Escherichia coli/Shigella clade. This approach recovered hundreds of previously
      unrecognized pseudogenes and showed that pseudogenes are a regular feature of
      bacterial genomes, even in those whose original annotations registered no
      truncated or otherwise inactivated genes. In Shigella flexneri 2a, large
      proportions of pseudogenes are generated by nonsense mutations and IS element
      insertions, events that seldom produce the pseudogenes present in the other
      genomes examined. Almost all (>95%) pseudogenes are restricted to only one of the
      genomes and are of relatively recent origin, suggesting that these bacteria
      possess active mechanisms to eliminate nonfunctional genes.

PMID- 15479950
TI  - Cell-to-cell contact influences proliferative marker expression and apoptosis in
      MIN6 cells grown in islet-like structures.
AB  - Cell-to-cell interactions play an important role in the development and
      maintenance of the beta-cell phenotype. Here, we have investigated whether E
      cadherin plays a role in regulating the growth of insulin-secreting MIN6 cells
      configured as three-dimensional islet-like clusters (pseudoislets). Pseudoislets
      form by cell aggregation rather than by proliferation from individual cells and
      attain the size of primary mouse islets after approximately 7 days of maintenance
      in culture. E-cadherin is known to mediate homotypic cell adhesion between beta
      cells and has also been implicated in a number of cellular processes, including
      proliferation, apoptosis, and differentiation. E-cadherin and its associated
      intracellular elements, alpha- and beta-catenin, were upregulated in MIN6
      pseudoislets. Pseudoislet formation was associated with an increased expression
      of cyclin-dependent kinase inhibitors and a concomitant downregulation of Ki67,
      suggesting an overall reduction in cellular proliferation. However, measurements
      of 5-bromo-2'-deoxyuridine incorporation revealed that there were no differences
      in the rate of MIN6 cell proliferation whether they were configured as monolayers
      or as pseudoislets, which is likely to be a result of their being a transformed
      cell line. Cells within pseudoislets were not necrotic, but apoptosis appeared to
      be upregulated in the islet-like structures. However, no differential expression
      of Fas and FasL was detected in monolayers and pseudoislets. These results
      suggest that cell-to-cell interactions within islet-like structures may initiate
      antiproliferative and proapoptotic signals.

PMID- 15479951
TI  - Beta2-agonist administration increases sarcoplasmic reticulum Ca2+-ATPase
      activity in aged rat skeletal muscle.
AB  - Aging is associated with a slowing of skeletal muscle contractile properties,
      including a decreased rate of relaxation. In rats, the age-related decrease in
      the maximal rate of relaxation is reversed after 4-wk administration with the
      beta2-adrenoceptor agonist (beta2-agonist) fenoterol. Given the critical role of
      the sarcoplasmic reticulum (SR) in regulating intracellular Ca2+ transients and
      ultimately the time course of muscle contraction and relaxation, we tested the
      hypothesis that the mechanisms of action of fenoterol are mediated by alterations
      in SR proteins. Sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) kinetic properties
      were assessed in muscle homogenates and enriched SR membranes isolated from the
      red (RG) and white (WG) portions of the gastrocnemius muscle in adult (16 mo) and
      aged (28 mo) F344 rats that had been administered fenoterol for 4 wk (1.4
      mg/kg/day ip, in saline) or vehicle only. Aging was associated with a 29%
      decrease in the maximal activity (Vmax) of SERCA in the RG but not in the WG
      muscles. Fenoterol treatment increased the Vmax of SERCA and SERCA1 protein
      levels in RG and WG. In the RG, fenoterol administration reversed an age-related
      selective nitration of the SERCA2a isoform. Our findings demonstrate that the
      mechanisms underlying age-related changes in contractile properties are fiber
      type dependent, whereas the effects of fenoterol administration are independent
      of age and fiber type.

PMID- 15479952
TI  - Tacrolimus suppresses glucose-induced insulin release from pancreatic islets by
      reducing glucokinase activity.
AB  - Tacrolimus is widely used for immunosuppressant therapy, including various organ
      transplantations. One of its main side effects is hyperglycemia due to reduced
      insulin secretion, but the mechanism remains unknown. We have investigated the
      metabolic effects of tacrolimus on insulin secretion at a concentration that does
      not influence insulin content. Twenty-four-hour exposure to 3 nM tacrolimus
      reduced high glucose (16.7 mM)-induced insulin secretion (control 2.14 +/- 0.08
      vs. tacrolimus 1.75 +/- 0.02 ng.islet(-1).30 min(-1), P < 0.01) without affecting
      insulin content. In dynamic experiments, insulin secretion and NAD(P)H
      fluorescence during a 20-min period after 10 min of high-glucose exposure were
      reduced in tacrolimus-treated islets. ATP content and glucose utilization of
      tacrolimus-treated islets in the presence of 16.7 mM glucose were less than in
      control (ATP content: control 9.69 +/- 0.99 vs. tacrolimus 6.52 +/- 0.40
      pmol/islet, P < 0.01; glucose utilization: control 103.8 +/- 6.9 vs. tacrolimus
      74.4 +/- 5.1 pmol.islet(-1).90 min(-1), P < 0.01). However, insulin release from
      tacrolimus-treated islets was similar to that from control islets in the presence
      of 16.7 mM alpha-ketoisocaproate, a mitochondrial fuel. Glucokinase activity,
      which determines glycolytic velocity, was reduced by tacrolimus treatment
      (control 65.3 +/- 3.4 vs. tacrolimus 49.9 +/- 2.8 pmol.islet(-1).60 min(-1), P <
      0.01), whereas hexokinase activity was not affected. These results indicate that
      glucose-stimulated insulin release is decreased by chronic exposure to tacrolimus
      due to reduced ATP production and glycolysis derived from reduced glucokinase
      activity.

PMID- 15479953
TI  - Is aldosterone synthesized within the rat brain?
AB  - Very small amounts of adrenocorticosteroids are synthesized by brain tissue in
      vitro. While there is evidence suggesting that the synthesis of aldosterone in
      the brain may have a role in the hypertension of the Dahl salt-sensitive rat, the
      de novo synthesis of aldosterone or corticosterone within the brain of a living
      animal has not been demonstrated. We have used sensitive ELISAs to measure
      aldosterone and corticosterone in the plasma and whole brains of intact rats
      receiving a normal-, low-, or high-salt diet to alter adrenal aldosterone
      production and of adrenalectomized rats provided sodium replacement, some of
      which received aldosterone, corticosterone, or DOC replacement. The results of
      several experiments were consistent. In intact rats, the brain concentration of
      aldosterone and corticosterone reflected that in the plasma. However, whereas
      aldosterone and corticosterone were undetectable or barely undetectable in the
      plasma of adrenalectomized animals, as was the corticosterone in their brains,
      aldosterone was consistently found in the brains of adrenalectomized rats,
      ranging from a mean of 6.6-41 pg/g, depending on the experiment. Provision of DOC
      as substrate for the endogenous aldosterone synthase and 11beta-hydroxylase did
      not significantly increase brain aldosterone or corticosterone content. It is
      postulated that the small amounts of aldosterone synthesized in the brain could
      provide a local ligand for autocrine or paracrine activation of the
      mineralocorticoid receptor.

PMID- 15479954
TI  - Beta-cell function and islet morphology in normal, obese, and obese beta-cell
      mass-reduced Gottingen minipigs.
AB  - Herein, we bridge beta-cell function and morphology in minipigs. We hypothesized
      that different aspects of beta-cell dysfunction are present in obesity and
      obesity with reduced beta-cell mass by using pulsatile insulin secretion as an
      early marker. Measures for beta-cell function (glucose and arginine stimulation
      plus baseline and glucose-entrained pulsatile insulin secretion) and islet
      morphology were studied in long-term (19-20 mo) obese (n = 5) and obese beta-cell
      reduced [nicotinamide + streptozotocin (STZ), n = 5] minipigs and normal
      controls, representing different stages in the development toward type 2
      diabetes. Acute insulin response (AIR) to glucose and arginine were,
      surprisingly, normal in obese (0.3 g/kg glucose: AIR = 246 +/- 119 vs. 255 +/- 61
      pM in control; 67 mg/kg arginine: AIR = 230 +/- 124 vs. 214 +/- 85 pM in control)
      but reduced in obese-STZ animals (0.3 g/kg glucose: AIR = 22 +/- 36, P < 0.01;
      arginine: AIR = 87 +/- 92 pM, P < 0.05 vs. control). Baseline pulsatile insulin
      secretion was reduced in obese (59 +/- 16 vs. 76 +/- 16% in control, P < 0.05)
      and more so in obese-STZ animals (43 +/- 13%, P < 0.01), whereas regularity
      during entrainment was increased in obese animals (approximate entropy: 0.85 +/-
      0.14 vs. 1.13 +/- 0.13 in control, P < 0.01). Beta-cell mass (mg/kg body wt) was
      normal in obese and reduced in obese-STZ animals, with pancreatic fat
      infiltration in both groups. In conclusion, obesity and insulin resistance are
      not linked with a general reduction of beta-cell function, but dynamics of
      insulin secretion are perturbed. The data suggest a sequence in the development
      of beta-cell dysfunction, with the three groups representing stages in the
      progression from normal physiology to diabetes, and assessment of pulsatility as
      the single most sensitive marker of beta-cell dysfunction.

PMID- 15479956
TI  - More than arterial embolisation.

PMID- 15479955
TI  - Chronic exposure to beta-hydroxybutyrate inhibits glucose-induced insulin release
      from pancreatic islets by decreasing NADH contents.
AB  - To investigate the effects of chronic exposure to ketone bodies on glucose
      induced insulin secretion, we evaluated insulin release, intracellular Ca2+ and
      metabolism, and Ca2+ efficacy of the exocytotic system in rat pancreatic islets.
      Fifteen-hour exposure to 5 mM d-beta-hydroxybutyrate (HB) reduced high glucose
      induced insulin secretion and augmented basal insulin secretion. Augmentation of
      basal release was derived from promoting the Ca2+-independent and ATP-independent
      component of insulin release, which was suppressed by the GDP analog. Chronic
      exposure to HB affected mostly the second phase of glucose-induced biphasic
      secretion. Dynamic experiments showed that insulin release and NAD(P)H
      fluorescence were lower, although the intracellular Ca2+ concentration
      ([Ca2+](i)) was not affected 10 min after exposure to high glucose. Additionally,
      [Ca2+](i) efficacy in exocytotic system at clamped concentrations of ATP was not
      affected. NADH content, ATP content, and ATP-to-ADP ratio in the HB-cultured
      islets in the presence of high glucose were lower, whereas glucose utilization
      and oxidation were not affected. Mitochondrial ATP production shows that the
      respiratory chain downstream of complex II is not affected by chronic exposure to
      HB, and that the decrease in ATP production is due to decreased NADH content in
      the mitochondrial matrix. Chronic exposure to HB suppresses glucose-induced
      insulin secretion by lowering the ATP level, at least partly by inhibiting ATP
      production by reducing the supply of NADH to the respiratory chain. Glucose
      induced insulin release in the presence of aminooxyacetate was not reduced, which
      implies that chronic exposure to HB affects the malate/aspartate shuttle and thus
      reduces NADH supply to mitochondria.

PMID- 15479957
TI  - Arterial embolisation in intractable primary post-partum haemorrhage: case
      series.
AB  - OBJECTIVE: To evaluate the efficacy and safety of arterial embolisation in the
      management of intractable primary post-partum haemorrhage. DESIGN. Retrospective
      case series. SETTING: Regional hospital, Hong Kong. PATIENTS: Nine patients aged
      28 to 39 years who were treated for severe primary post-partum haemorrhage
      between October 2000 and January 2003. INTERVENTION: Emergency transcatheter
      arterial embolisation. MAIN OUTCOME MEASURES: Clinical outcome and complications.
      RESULTS: All nine arterial embolisations successfully arrested the haemorrhage.
      The main cause of primary post-partum haemorrhage was uterine atony. No serious
      complication arose, although one patient experienced slight numbness of the right
      leg. Normal menstruation resumed in all patients, except for the one who had had
      a hysterectomy as initial treatment. One patient became pregnant 1 year after
      embolisation. Patients were followed up for 10 months. CONCLUSION: In our
      experience, arterial embolisation is safe and efficacious, and is the treatment
      of choice for patients with intractable primary post-partum haemorrhage.

PMID- 15479958
TI  - The prevalence of microalbuminuria among patients with type II diabetes mellitus
      in a primary care setting: cross-sectional study.
AB  - OBJECTIVES: To determine the prevalence of microalbuminuria among patients with
      type II diabetes mellitus in a primary care setting, and to study the association
      between various risk factors and the presence of microalbuminuria. DESIGN: Cross
      sectional community-based study. SETTING: Four primary care clinics, Hong Kong.
      PATIENTS: All patients with type II diabetes mellitus who regularly attended the
      clinics between May 2002 and March 2003. MAIN OUTCOME MEASURES: Patients'
      demographic data, the proportion with microalbuminuria (measured using a spot
      urine test), and the association between this condition and risk factors for
      diabetic nephropathy (via correlation and multivariable logistic regression
      analysis). RESULTS: The mean age of the 1161 patients in the sample population
      was 58.0 years. The mean duration of diabetes mellitus was 5.7 years, and the
      mean level of glycated haemoglobin was 7.4%. A total of 13.4% of the patients had
      microalbuminuria. Having the condition was significantly associated with advanced
      age, female sex, poor glycaemic control, and coexisting hypertension in both
      correlation and regression analyses. No significant association with ever smoking
      was found. CONCLUSION: Early screening for incipient diabetic nephropathy and
      aggressive management of modifiable risk factors in a primary care setting may be
      important in optimising the renal outcome of patients with type II diabetes
      mellitus.

PMID- 15479959
TI  - Short-stay in-patient rehabilitation of elderly patients with chronic obstructive
      pulmonary disease: prospective study.
AB  - OBJECTIVES: To evaluate the effectiveness of a short-stay in-patient
      rehabilitation programme. DESIGN: Prospective case-control cohort study. SETTING:
      Regional medical centre, Hong Kong. PATIENTS: One hundred and thirty symptomatic
      elderly patients with chronic obstructive pulmonary disease who had been treated
      for an acute respiratory illness in 1998. They were divided into two groups: the
      conventional treatment group, which received no rehabilitation (n=65), and the
      rehabilitation group (n=65). INTERVENTION: A short-stay in-patient rehabilitation
      programme was implemented, which included assessment, patient and caregiver
      education, an exercise regimen, physiotherapy, occupational therapy, and case
      conference. MAIN OUTCOME MEASURES: Length of stay, hospital re-admission rate,
      and admission-free interval. RESULTS: The mean length of stay in the
      rehabilitation ward was 6.2 days. The rate of hospital re-admission was
      significantly higher in the conventional treatment group than in the
      rehabilitation group, both within 28 days of discharge home (relative risk=3.33;
      95% confidence interval, 2.32-4.56; P=0.019) and at 100 days after discharge
      (relative risk=2.47; 95% confidence interval, 1.78-3.48; P<0.001). The admission
      free interval was significantly longer in the rehabilitation group than in the
      conventional treatment group (1.13 years vs 0.86 years; P<0.001). CONCLUSION: A
      short-stay in-patient rehabilitation programme is effective in reducing hospital
      re-admission rates. This type of rehabilitation service may be important for
      elderly patients, as well as for patients with more advanced disease and more
      functional deficits than others.

PMID- 15479960
TI  - Suicides in general hospitals in Hong Kong: retrospective study.
AB  - OBJECTIVE: To describe the characteristics of suicidal patients and their
      suicidal acts occurring in general wards. DESIGN: Retrospective study. SETTING:
      All general public hospitals in Hong Kong. PATIENTS: Survey data based on
      hospital records of patients who died of suicide or who attempted suicide in
      general wards between 2000 and 2002 were studied. MAIN OUTCOME MEASURES:
      Demographic information, medical history, and circumstances of the suicidal acts.
      RESULTS: Twenty-six hospitals reported a total of 166 suicidal acts, which
      included 34 completed suicides, corresponding to 9.46 attempted suicides and 1.93
      completed suicides per 100 000 admissions. Most suicidal acts occurred in medical
      wards. Patients were, on average, in their mid-50s, predominantly male, and had
      been admitted because of physical problems. Fewer than 20% were admitted because
      of attempted suicide. A significant proportion of suicide attempters used
      potentially lethal suicide methods in the wards. Wide ranges of objects were used
      in the suicidal acts. Completed suicides tended to occur after midnight and in
      the ward toilet. Patients who went missing and then committed suicide acts did so
      in the first few hours of leaving the hospital. The timing of suicidal acts
      varied greatly with the reasons of admission. CONCLUSION: Prevention efforts in
      general wards are unlikely to be effective if they simply focus on patients
      admitted for attempted suicide, or on the restriction of suicide means. For
      patients admitted to general wards because of attempted suicide, the risk is
      highest just after admission; hence, these patients have to be monitored closely.
      A high degree of alertness to the possibility of depression and suicidal risk
      among general ward patients is required.

PMID- 15479961
TI  - Impact of severe respiratory syndrome on anxiety levels of front-line health care
      workers.
AB  - OBJECTIVE: To identify anxiety levels among front-line health care workers during
      the 2003 severe acute respiratory syndrome outbreak. DESIGN: Questionnaire
      survey. SETTING: Regional hospital, Hong Kong. PARTICIPANTS: All hospital staff
      were given a questionnaire; administrative staff who had not had any patient
      contact served as controls. MAIN OUTCOME MEASURES: Levels of contact with
      patients who had severe acute respiratory syndrome were measured and correlated
      with anxiety levels as determined by the State-Trait Anxiety Inventory. RESULTS:
      Of 4252 questionnaires distributed between May and June 2003, 2040 (48.0%) were
      returned and 1926 (45.3%) were valid for analysis. Overall, 534 (27.7%)
      respondents had had contact with patients with severe acute respiratory syndrome.
      Anxiety scores ranged from 20 to 80, and mean (standard deviation) scores were
      higher among staff who had had contact with patients with severe acute
      respiratory syndrome than among those who had not (52.6 [10.5] versus 49.8
      [10.1], respectively; P<0.01). Mean anxiety levels were higher among workmen,
      health care assistants, and nurses than among administrative staff controls or
      doctors (P<0.01). Anxiety scores were correlated with burnout scores (Pearson's
      correlation coefficient, 0.52-0.59) and with discomfort from wearing protective
      gear (0.21-0.32). CONCLUSION: Severe acute respiratory syndrome has likely
      stressed the public health care system. Prediction and early identification of
      adverse factors in a crisis situation would allow early implementation of
      interventions to reduce and counteract the impact of this stress.

PMID- 15479962
TI  - An update on the aetiology of orofacial clefts.
AB  - OBJECTIVE: To review recent data on the aetiology of cleft lip and palate. DATA
      SOURCES: MEDLINE literature search (1986-2003). STUDY SELECTION: Literature and
      data on aetiology of cleft lip and palate using the following key words: 'cleft
      lip', 'cleft palate', 'aetiology', and 'genetics'. DATA EXTRACTION: Relevant
      information and data were reviewed by the authors. DATA SYNTHESIS: Cleft lip and
      palate is one of the most common types of congenital malformation. The aetiology
      seems complex, but genetics plays a major role. Recently several genes causing
      syndromic cleft lip and palate have been discovered. Three of them--namely T-box
      transcription factor-22 (TBX22), poliovirus receptor like-1 (PVRL1), and
      interferon regulatory factor-6 (IRF6)--are responsible for causing X-linked cleft
      palate, cleft lip/palate-ectodermal dysplasia syndrome, and Van der Woude's and
      popliteal pterygium syndromes, respectively; they are also implied in non
      syndromic cleft lip and palate. The nature and function of these genes vary
      widely, illustrating high vulnerability within the craniofacial developmental
      pathways. The aetiological complexity of non-syndromic cleft lip and palate is
      also exemplified by the large number of candidate genes and loci. CONCLUSIONS:
      The aetiology of non-syndromic cleft lip and palate is still largely unknown, but
      mutations in candidate genes have already been identified in a small proportion
      of cases of non-syndromic cleft lip and palate. Determining the relative risk of
      cleft lip and palate, on the basis of genetic background and environmental
      influence, including smoking, alcohol use, and dietary factors, will aid in
      genetic counselling and the development of future preventive measures.

PMID- 15479963
TI  - Update of the management of postoperative endophthalmitis.
AB  - Postoperative endophthalmitis is a rare but potentially devastating complication
      of intra-ocular surgery. Most cases are caused by bacterial infection. The
      clinical presentation of endophthalmitis can be classified as acute postoperative
      endophthalmitis, chronic postoperative endophthalmitis, and bleb-associated
      endophthalmitis. They each have a different aetiology, treatment, and prognosis.
      This review discusses these features, as well as the microbiology, diagnosis, and
      treatment outcomes of these three types of inflammation, with particular emphasis
      on recent advances in their management. The role of steroids, systemic
      fluoroquinolones, and the choice of antibiotic against gram-negative bacteria are
      still controversial and need further study. Moreover, the management of chronic
      postoperative and bleb-associated endophthalmitis has not been standardised, and
      no conclusive findings on the efficacy of the various prophylactic measures are
      available. Thus, the treatment and prevention of postoperative endophthalmitis
      remain a clinical challenge.

PMID- 15479964
TI  - Infective thyroiditis in two cases of systemic lupus erythematosus.
AB  - We report on two patients with systemic lupus erythematosus, both of whom
      developed suppurative thyroiditis. One suffered from Staphylococcus aureus
      induced thyroiditis and the other had tuberculous thyroiditis. The occurrence of
      tuberculous thyroiditis in systemic lupus erythematosus has not previously been
      reported. The diagnoses were made by fine-needle aspiration biopsy and subsequent
      bacteriological confirmation. Transient alteration of thyroid function was
      observed in both patients. In patients with systemic lupus erythematosus who
      present with fever and anterior neck pain, infection of the thyroid gland should
      be considered, and appropriate investigations undertaken.

PMID- 15479965
TI  - A case of severe haemolytic disease of the newborn due to anti-Di(a) antibody.
AB  - Red cell allo-antibodies directed against the Diego (Di) blood group antigen have
      rarely been reported to cause a haemolytic reaction against transfusion or
      haemolytic disease of the newborn. The frequency of the Di(a+) phenotype among
      the Hong Kong Chinese population is estimated to be 4.4%. We report on a case of
      severe haemolytic disease of the newborn due to anti-Di(a) antibody--the first
      local case to the best of our knowledge. Rare but clinically significant
      antibodies targeting red blood cells have to be considered in the investigation
      of haemolytic disease of the newborn when common underlying factors have been
      eliminated.

PMID- 15479966
TI  - Jervell-Lange Nielsen syndrome in a Pakistani family.
AB  - Congenital long QT syndrome is a rare hereditary disease that is related to the
      dysfunction of ion channels in cardiac cells. We report on a very rare case of
      its autosomal recessive form--the Jervell-Lange Nielsen syndrome--in a Pakistani
      family, which was diagnosed after the incidental finding of bradycardia in a
      newborn baby girl. We discuss the range of presentations in neonates; the
      importance of strong suspicion of the syndrome and family screening; the use of
      the diagnostic criteria and genetic tests; and the different management
      strategies.

PMID- 15479967
TI  - Chronic abdominal pain in a Chinese woman with spastic cerebral palsy.
AB  - Pain affects people's activities of daily living especially among those with
      cerebral palsy. We report a case of a woman with spastic cerebral palsy who
      presented with chronic abdominal pain. The principles of multidisciplinary pain
      management are highlighted and the difficulties when dealing with patients with
      special needs are discussed.

PMID- 15479968
TI  - Sartans for hypertension--implications of the Valsartan Antihypertensive Long
      term Use Evaluation (VALUE) trial.

PMID- 15479969
TI  - A case of Potter syndrome due to posterior urethral valve.

PMID- 15479970
TI  - The evolution of complaint management in the Hong Kong Hospital Authority. Part
      2: the 'complaints' iceberg.

PMID- 15479971
TI  - Use of hair analysis in diagnosing heavy metal poisoning.

PMID- 15479972
TI  - Looking into the pregnant woman's eye.

PMID- 15479974
TI  - Hyperuricaemia and cardiovascular disease.

PMID- 15479975
TI  - Combined pulse oximetry/cutaneous carbon dioxide tension monitoring during
      colonoscopies: pilot study with a smart ear clip.
AB  - BACKGROUND: We compared the accuracy and practicability of a new combined ear
      sensor device measuring pulse oximetry and transcutaneous carbon dioxide tension.
      METHODS: Validation studies were done by comparing the results of the combined
      sensor with arterial blood gas measurements. In an observational part, monitoring
      data were obtained from 25 patients undergoing colonoscopy, sedated with
      midazolam and alfentanil and from 8 patients without sedation. RESULTS: There was
      an excellent correlation between the oxygen saturation and carbon dioxide tension
      measurements comparing the combined sensor with arterial blood gas analysis (R
      0.96 and 0.93, respectively). A mean rise in transcutaneous carbon dioxide
      tension of 7.6 mm Hg was detectable during sedation with midazolam/alfentanil and
      of 2.3 mm Hg without sedation. CONCLUSION: Combined POX/PcCO2 monitoring at the
      ear lobe is a novel approach to improve patient safety during sedation and may be
      helpful in preventing an unintentional slide into a state of deep sedation with
      impairment of ventilation.

PMID- 15479976
TI  - Improvement of gastric motility with gastric electrical stimulation in STZ
      induced diabetic rats.
AB  - AIMS: The aims of this study were to observe whether gastric motility was
      impaired in streptozotocin (STZ)-induced diabetic rats and whether gastric
      electrical stimulation was able to restore the impaired motility. METHODS: Ten
      control rats and 30 STZ-induced diabetic rats were used in this study. Gastric
      slow waves were recorded at baseline and 0, 1, 2, 3 and 4 weeks after the
      injection of STZ or vehicle. Gastric emptying with (long or short pulses) or
      without gastric electrical stimulation was measured 6 weeks after STZ injection
      in a group of 10 diabetic rats each. RESULTS: (1) STZ injection resulted in
      hyperglycemia and weight loss. (2) Gastric motility was impaired in the diabetic
      rats. The percentage of normal slow waves was progressively reduced 2 weeks after
      STZ injection. Compared with the control rats, gastric emptying in the diabetic
      rats was significantly delayed 6 weeks after STZ injection (60 +/- 3 vs. 79 +/-
      2%, p < 0.02). (3) Gastric electrical stimulation with either long or short
      pulses accelerated gastric emptying in the diabetic rats. (4) Gastric electrical
      stimulation with long but not short pulses was capable of normalizing gastric
      dysrhythmia in the diabetic rats. CONCLUSION: Our data show that gastric motility
      is impaired in STZ-induced diabetic rats as reflected by a progressive reduction
      in the percentage of normal gastric slow waves and delayed gastric emptying.
      Moreover, here we show that gastric electrical stimulation normalizes delayed
      gastric emptying in diabetic rats and this normalization is not attributed to the
      effect of gastric electrical stimulation on gastric slow waves.

PMID- 15479977
TI  - Clinical usefulness of serum pepsinogen II in the management of Helicobacter
      pylori infection.
AB  - BACKGROUND: Serum pepsinogen II (sPGII) levels are known to increase during
      Helicobacter pylori infection. AIM: To assess H. pylori infection and success of
      H. pylori therapy by means of sPGII levels. METHODS: sPGII levels were determined
      in 156 H. pylori-positive and 157 H. pylori-negative consecutive patients with
      dyspeptic symptoms. Additionally, sPGII determination was performed in 70 H.
      pylori-positive patients 2 months after H. pylori eradication therapy. In 29 of
      these 70 patients, gastroscopy was performed to evaluate the effect of H. pylori
      therapy on gastric activity. RESULTS: H. pylori-positive subjects demonstrated a
      significantly higher mean of sPGII levels than H. pylori-negative subjects (16.8
      +/- 7.4 vs. 8.6 +/- 3.7 microg/l; p < 0.001). The best sPGII cut-off for
      predicting H. pylori infection was 9.93 microg/l (sensitivity 83%, specificity
      73%). The best cut-off values to evaluate success of therapy were: sPGII of 9.47
      microg/l, a sPGII variation level (difference between baseline and after therapy)
      of 4.54 microg/l, and a sPGII Deltavalue (sPGII variation divided by sPGII before
      therapy) of 25% (sensitivity 93%, specificity 91%). CONCLUSIONS: sPGII levels may
      be used as a reliable marker of H. pylori infection in the initial diagnosis as
      well as to evaluate H. pylori eradication and subsequent changes in gastric
      inflammation.

PMID- 15479978
TI  - CT air-contrast enema as a preoperative examination for colorectal cancer.
AB  - BACKGROUND/AIMS: We conducted a study on three-dimensional computed tomography
      (CT) images, in particular CT air-contrast enema (CT enema), using multidetector
      row CT (MDCT), to see whether CT enema is useful as a preoperative examination
      for colorectal cancer. We aimed to evaluate the detectability of lesions and the
      depth of cancer invasion using CT enema. METHODS: 292 patients (328 lesions) with
      colorectal cancer were enrolled. After an adequate insufflation of the large
      intestine, MDCT scans were performed. With the data obtained by MDCT, we
      reconstructed CT enema images. CT enema images were assessed for the
      detectability of lesions. The depth of invasion was evaluated by the deformity of
      the lesion on profile images. The deformities were divided into five groups: no
      deformity, slight deformity, mild deformity, moderate deformity and severe
      deformity. RESULTS: The detectability of lesions was 97.3%. The reasons for
      undetectability were due to residual fluid in 8 cases and insufficient colonic
      distention in 1 case. As the depth of invasion increased, the grade of the
      deformity became severer (p < 0.0001). CONCLUSIONS: CT enema proved to be an
      excellent examination tool to detect lesions. The deformity demonstrated by CT
      enema could be an additional source of information to predict the depth of
      invasion.

PMID- 15479979
TI  - Jakob-Creutzfeldt disease.

PMID- 15479980
TI  - Antibody-induced failure of botulinum toxin type B therapy in de novo patients.
AB  - Botulinum toxin type B (BT-B) therapy failure due to formation of botulinum toxin
      type B antibodies (BT-B-AB) has only been reported in patients with botulinum
      toxin type A antibodies (BT-A-AB). We are reporting BT-B-AB-induced therapy
      failure in 2 patients with no previous exposure to botulinum toxin. In patient 1
      complete therapy failure occurred after a single exposure to 14,400 mouse units
      (MU) BT-B (NeuroBloc). The mouse diaphragm assay (MDA) revealed a BT-B-AB titre
      in excess of 10 mU/ml. Doubling the BT-B dose did not elicit any effects.
      Application of 360 MU BT-A (Botox) produced the original therapeutic effect, but
      the second BT-A application was followed by partial and the third by complete
      therapy failure. Doubling the BT-A dose did not elicit any effects. MDA testing
      showed a BT-A-AB titre in excess of 10 mU/ml. In patient 2 a single exposure to
      7,200 MU BT-B lead to a complete therapy failure. MDA testing revealed a BT-B-AB
      titre in excess of 10 mU/ml. Doubling the BT-B dose did not elicit any effects.
      Application of 180 MU BT-A (Botox) produced the original response on 3
      consecutive applications. Antibody formation can occur after a single exposure to
      botulinum toxin. However, this is highly unusual. Since therapy failure occurred
      after the first-ever botulinum toxin exposure, short intervals between injections
      and use of booster injections can be excluded as causes for BT-B-AB formation in
      both patients. A more likely cause may be the substantially higher amount of
      antigenic protein administered in BT-B therapy compared to BT-A therapy. Further
      studies are necessary to compare the incidence of antibody formation in BT-B and
      BT-A therapy.

PMID- 15479981
TI  - Evaluation of maximal respiratory pressures in myasthenia gravis. Prognostic
      value.
AB  - We assess the prognosis of mild forms of myasthenia gravis (MG) by maximal
      respiratory pressures (MRP) and single fiber electromyography (SFEMG). Fifty MG
      patients (12 form I, 21 form IIa and 17 form IIb) are valued by MRP [maximal
      expiratory pressure (MEP) and maximal inspiratory pressure (MIP)] and SFEMG, and
      are followed-up clinically. We have found in form I patients developing form IIa
      and form IIa worsening to form IIb, MEP and MIP mean relative values
      significantly lower than the rest. Inversely, IIb form patients improving to IIa
      form display MIP mean relative values higher than the rest; no difference appears
      with MEP. A reduction under 50% of fifth-percentile implies clinical
      deterioration in forms I and IIa, while its surpassing in IIb form suggests a
      tendency to improvement. No evident differences are found by SFEMG. MRP allow the
      follow-up of MG patients and could warn us of a clinical prognosis.

PMID- 15479982
TI  - Thromboembolic complications of intravenous immunoglobulin treatment.
AB  - Intravenous immunoglobulin (IVIg) preparations are increasingly being used in the
      treatment of neuroautoimmune diseases. Although for most part this treatment is
      safe, serious side effects such as thromboembolic events have been reported. We
      report on 7 patients who suffered a thromboembolic event while being treated with
      IVIg. Four patients suffered a stroke or transient ischemic attack, 1 an inferior
      wall myocardial infarction, 1 a deep venous thrombosis, and 1 a retinal artery
      infarct. The age range of the patients was 57-81 and most had underlying risk
      factors, such as hypertension, hypercholesterolemia, atrial fibrillation, history
      of vascular disease and stroke, and deep venous thrombosis. Three patients
      received multiple IVIg infusions before suffering a thromboembolic complication.
      Therefore, the clinicians should be vigilant about the possibility of
      thromboembolic complications with each IVIg infusion and be especially judicious
      with the use of IVIg in patients with underlying risk factors.

PMID- 15479983
TI  - Adenoid cystic carcinoma of Bartholin's Gland. Case report with review of the
      literature.
AB  - Adenoid cystic carcinoma of Bartholin's gland is characterized by slow growth,
      local invasion, and sometimes distant metastasis. There is no consensus regarding
      the optimal treatment. We report herein a rare case of stage II adenoid cystic
      carcinoma of Bartholin's gland that was successfully treated by wide local
      excision of the tumor and ipsilateral inguinal and pelvic lymphadenectomy. A 54
      year-old Japanese woman was admitted complaining of painless, gradually
      increasing vulvar mass existing from ten years before. Local examination revealed
      a 3 x 2-cm hard mass in the left labium major. Pathological examination of
      subsequent excisional biopsy revealed adenoid cystic carcinoma originating in the
      Bartholin's gland. A wide local resection of the tumor with inguinal and pelvic
      lymphadenectomy was performed. The tumor was completely excised with free
      margins. There was no metastasis in the resected lymph nodes. The patient was
      diagnosed as having stage II vulvar cancer according to the International
      Federation of Gynecologists and Obstetricians classification (1988). The patient
      is now healthy without evidence of recurrence at 5 years after surgery. Adenoid
      cystic carcinoma of Bartholin's cyst at early stage can be treated by wide local
      excision as a primary surgery.

PMID- 15479984
TI  - Ligation of the uterine artery and early postnatal food restriction - animal
      models for growth retardation.
AB  - Intrauterine growth restriction (IUGR) is one of the major causes of short
      stature in child- and adulthood. The cause of IUGR is unknown, however, an
      impaired uteroplacental function during the second half of human pregnancy might
      be an important factor, by affecting the programming of somatotropic axis and
      leading to postnatal growth failure into adulthood. Two rat models with
      perinatally induced growth retardation were used to examine the long-term effects
      of perinatal insults on growth. IUGR rats were prepared from pregnant dams, with
      a bilateral uterine artery ligation at day 17 of their pregnancy. Since the rat
      is relatively immature at birth, an early postnatal food restriction model was
      included as another model to broaden the time window of sensitive period of
      organogenesis. An individual growth curve was calculated of each animal (n =
      813). From these individual growth curves the predicted growth curve for each
      experimental group was calculated by multilevel analysis. The proposed
      mathematical model allows us to estimate the growth potentials of these rat
      models with precision and could provide basic information to investigate the
      relationships among a number of other variables in future studies. Furthermore,
      we concluded that both pre- and early postnatal malnutrition leads to
      irreversible slowing down of postnatal growth.

PMID- 15479985
TI  - Role of endothelial mitochondria in oxidant production and modulation of
      neutrophil adherence.
AB  - This study is designed to test whether the postanoxic endothelial mitochondria is
      an important source of reactive oxygen species (ROS) using a chemical model of
      mitochondrial disruption to mimic the loss of mitochondrial integrity after
      anoxia/reoxygenation (A/R). The current objectives were to (1) determine the
      adhesion of human neutrophils to human umbilical vein endothelial cells exposed
      to antimycin A, a specific inhibitor of the mitochondrial cytochrome b-c(1)
      complex, and (2) define the mechanisms responsible for the early and late phases
      of neutrophil hyperadhesivity. Antimycin A caused a 5-fold increase in ROS
      generation and induced neutrophil adhesion at 30 min (phase 1) and 4 h (phase 2)
      that were quantitatively similar to that induced by A/R. Blockade of electron
      transport in antimycin A and A/R exposed cells with rotenone, amytal or
      thenoyltrifluoroacetate, but not myxothiazol, prevented neutrophil adhesion,
      confirming a role for mitochondrial ROS. Catalase inhibited phase 1 adhesion,
      indicating H(2)O(2) involvement. Anti-ICAM-1 or anti-P-selectin monoclonal
      antibodies (mAbs) attenuated phase 1 adhesion, while anti-E-selectin mAb
      attenuated phase 2 adhesion, consistent with roles for constitutive ICAM-1 and
      preformed P-selectin in early and E-selectin in late phase responses. Actinomycin
      D and cycloheximide or competing ds-oligonucleotides containing cognate DNA
      sequences of the nuclear factor kappaB or activator protein-1 attenuated phase 2
      adhesion, implicating a role for de novo protein synthesis. Peak surface
      expression of the endothelial cell adhesion molecules correlated with peak
      adhesions at phases 1 and 2. These results show that disruption of mitochondrial
      respiratory chain elicits ROS production that mediates transcription-independent
      and -dependent surface expression of various adhesion molecules that leads to a
      two-phase neutrophil-HUVEC interaction similar to that induced by A/R.

PMID- 15479986
TI  - How citation analysis can monitor the progress of research in clinical medicine.

PMID- 15479987
TI  - Dietary folate and the risk of depression in Finnish middle-aged men. A
      prospective follow-up study.
AB  - BACKGROUND: Several cross-sectional studies have focused on the low blood folate
      levels of depressive patients. Nevertheless, no prospective studies have been
      published on the association between dietary folate and depression. METHODS: We
      studied the association between dietary folate and cobalamin and receiving a
      discharge diagnosis of depression in a prospective follow-up setting. Our cohort
      was recruited between 1984 and 1989 and followed until the end of 2000, and it
      consisted of 2,313 men aged between 42 and 60 years from eastern Finland.
      RESULTS: The mean intake of folate in the whole cohort was 256 microg/day
      (SD=76). Those below the median of energy-adjusted folate intake had higher risk
      of getting discharge diagnosis of depression (RR 3.04, 95% CI: 1.58, 5.86) during
      the follow-up period than those who had a folate intake above the median. This
      excess risk remained significant after adjustment for current socioeconomic
      status, the baseline HPL depression score, the energy-adjusted daily intake of
      fibre and vitamin C, and the total fat intake. CONCLUSIONS: A low dietary intake
      of folate may be a risk factor for severe depression. This also indicates that
      nutrition may have a role in the prevention of depression.

PMID- 15479988
TI  - Vitamin B6 level is associated with symptoms of depression.
AB  - BACKGROUND: A low level of vitamin B6 might theoretically cause depression as
      vitamin B6 is a cofactor in the tryptophan-serotonin pathway. In the present
      study, we examined the association between depression and the phosphate
      derivative of vitamin B6 in plasma, pyridoxal phosphate (PLP). METHODS: In 140
      individuals, symptoms of depression were evaluated by the Major Depression
      Inventory, and biochemical markers of vitamin B deficiency were measured.
      RESULTS: We found that 18 (13%) individuals were depressed. A low plasma level of
      PLP was significantly associated with the depression score (p=0.002). No
      significant association was found between depression and plasma vitamin B12
      (p=0.13), plasma methylmalonic acid (p=0.67), erythrocyte folate (p=0.77), and
      plasma total homocysteine (p=0.16). CONCLUSION: Our study suggests that a low
      level of plasma PLP is associated with symptoms of depression. Randomized trials
      are now justified and needed in order to examine whether treatment with vitamin
      B6 may improve symptoms of depression.

PMID- 15479989
TI  - Prospective examination of anxiety persistence and its relationship to cardiac
      symptoms and recurrent cardiac events.
AB  - BACKGROUND: The current study builds on previous research demonstrating a link
      between anxiety and inhospital recurrent ischemic and arrhythmic events, by
      examining the effects of persistent anxiety on recurrent events 1 year later.
      METHODS: 913 patients with unstable angina (UA) and myocardial infarction (MI)
      from 12 coronary care units were recruited, and follow-up data were collected at
      6 and 12 months after the event. Measures included cardiac symptomatology,
      healthcare utilization, the anxiety subscale of the Primary Care Evaluation of
      Mental Disorders , the phobic anxiety subscale of the Middlesex Hospital
      Questionnaire, and the Beck Depression Inventory. RESULTS: Over one third of
      participants with UA and MI experienced elevated anxiety at the time of the
      ischemic event, and these symptoms persisted for 1 year in 50% of anxious
      participants. Although participants with anxiety reported more atypical cardiac
      symptomatology, the prevalence of typical cardiac symptoms such as chest pain did
      not differ based on anxiety. After controlling for the severity of the coronary
      event, family income, sex, diabetes, and smoking, the following variables were
      significantly predictive of self-reported recurrent cardiac events at 6 months or
      1 year: older age, family history of cardiovascular disease, greater depressive
      symptomatology at baseline, and anxiety at 6 months. Only 38% of anxious patients
      were asked about such symptoms, indicating underutilization of effective
      psychotherapeutic treatment. CONCLUSIONS: Over and above the effects of
      depressive symptomatology (among other confounding variables), nonphobic anxiety
      appears to have a negative effect on self-reported outcome following an ischemic
      coronary event. Anxiety symptomatology is underrecognized and undertreated, and
      examination of effects of treatment on secondary prevention must be pursued.

PMID- 15479990
TI  - Hypercoagulability in working men and women with high levels of panic-like
      anxiety.
AB  - BACKGROUND: There is growing evidence that cardiovascular diseases are relatively
      more prevalent in subjects who feel anxious. An increased clotting diathesis
      might subject anxious individuals to an elevated arterial thrombotic risk. We
      investigated whether panic-like anxiety would relate to a hypercoagulable state.
      METHODS: Study participants with a complete data set were 691 employees (mean age
      +/- SD 40 +/- 11 years, 83% men) recruited from two German companies. Subjects
      were asked to self-rate the onset of sudden feelings of panic in the previous
      week on a 4-point Likert scale: 0=not at all (n=416), 1=not very often (n=179),
      2=quite often (n=55), and 3=very often indeed (n=41). Levels of fibrinogen, of
      the antifibrinolytic enzyme type 1 plasminogen activator inhibitor (PAI-1), and
      of the hypercoagulability marker fibrin D-dimer were measured in plasma. RESULTS:
      While the level of D-dimer was significantly different across the 4 scores of
      panic feelings (F3, 687=6.49, p <0.001), the levels of fibrinogen and PAI-1 were
      not. After having controlled for a range of confounders of hemostatic function,
      the 96 subjects reporting panic feelings either 'quite often' or 'very often
      indeed' had higher D-dimer levels (mean +/- SEM 165 +/- 12.0 vs. 145 +/- 4.3
      ng/ml, F20, 670= 4.78, p=0.030) and lower fibrinogen levels (259 +/- 6.9 vs. 274
      +/- 2.5 mg/dl, F20, 670=4.71, p=0.030) than the 595 subjects reporting panic
      feelings either 'not at all' or 'not very often'. CONCLUSIONS: The findings
      suggest increased fibrin turnover with sudden feelings of panic. Prospective
      studies need to show whether such a procoagulant mechanism may contribute to the
      increased coronary risk with panic-like anxiety.

PMID- 15479991
TI  - Personality profile of HIV outpatients: preliminary results and remarks on
      clinical management.
AB  - BACKGROUND: Currently, HIV is one of the most widely spread epidemics in the
      world. The specificity of the mode of transmission, the well-known severity of
      the prognosis, and the kind of therapies used are peculiarities of this illness.
      Personality traits of individuals with HIV may influence conditions for the
      infection itself. On the other hand, it is possible that personality traits may
      influence the course of the illness and the willingness of the patients to adhere
      to treatment. The present study assessed the personality traits of a
      heterogeneous group of seropositive subjects compared with healthy controls to
      determine specific temperament and character traits of this population. METHODS:
      The Temperament and Character Inventory (TCI) was administered to 126 HIV
      positive outpatients belonging to different risk categories for HIV infection and
      to a sample of healthy individuals matched for sex, age, and socioeconomic
      parameters. RESULTS: Drug-dependent HIV-positive patients displayed higher scores
      in novelty seeking and harm avoidance and lower scores in self-directedness
      compared with healthy controls. Non-drug-dependent HIV-positive subjects scored
      significantly higher in self-transcendence. CONCLUSIONS: Temperament and
      character features significantly differentiate the HIV-positive subjects from
      controls and those belonging to the different risk categories for HIV infection.
      Drug-dependent subjects with HIV display more impulsiveness, which possibly
      predates the HIV infection. They are also more fearful and lack self
      directedness. Non-drug-dependent subjects express higher self-transcendence
      resources, possibly to overcome their difficulties. Both the temperament and
      character features may influence compliance with treatment and require specific
      interventions considering these subgroups.

PMID- 15479992
TI  - Mentalizing language development in a longitudinal attachment sample:
      implications for alexithymia.
AB  - BACKGROUND: The construct of alexithymia implies a deficit in symbolization for
      emotional, somatic, and mental states. However, the etiologic factors for
      alexithymia have not yet been fully elucidated. The present study investigated
      the use of mentalizing language, i.e. the utterance of internal states, from a
      developmental perspective according to attachment organization and
      disorganization. METHODS: A longitudinal design across 4 time points was applied
      to a volunteer sample of 42 children. At 12 months, children were tested with the
      strange situation procedure, the standard measure of attachment at the optimal
      age, and attachment classifications were taken of videotapes. At ages 17, 23, 30
      and 36 months, mother and child were observed in simplified separation episodes
      of 30 min duration. Transcripts of the sessions were subject to coding of
      internal state words. RESULTS: During the investigated span, securely attached
      children rapidly acquired emotion, physiology, cognition and emotion-regulatory
      language, whereas insecurely attached and disorganized children either completely
      lacked internal state language or displayed a considerable time lag in the use of
      emotion and cognition vocabulary. CONCLUSION: The results raise the possibility
      that alexithymia might be a consequence of deficits in the development of
      internal state language in the context of insecure or disorganized childhood
      attachment relationships.

PMID- 15479993
TI  - Affective correlates of occupational exposure to whole-body vibration. A case
      control study.
AB  - BACKGROUND: Exposure to whole-body vibrations (WBV) represents a highly diffuse
      occupational risk. Some studies report that chronic exposure to WBV induces a
      significant increment in the modifications of the cognitive and emotional area.
      The aim of this study was to investigate the long-term effects of WBV exposure on
      the neuropsychic and behavioural system. METHODS: The study population consisted
      of 137 male subjects, mean age 45.7 years, working as drivers of mechanical
      trolleys and occupationally exposed to WBV of a frequency below 2 m/s2. The
      Profile of Mood States was administered to all subjects in a maximum time of 10
      min and in the same operative conditions. The results were compared with those of
      a homogeneous control group by means of an innovative statistical technique.
      RESULTS: The results show a significant difference in the response to the
      neurobehavioural test. The exposed group showed, in fact, a higher score compared
      with the controls for all 6 factors. In particular, the scores for factors F
      (fatigue-inertia), D (depression-dejection) and T (tension-anxiety) were more
      elevated, expressing a significant alteration of the psycho-affective status.
      Moreover, statistical analysis showed a correlation between exposure time and the
      score obtained for all factors in the exposed group. CONCLUSION: This study
      indicates that occupational exposure to WBV is associated with alterations of
      mood status and that these modifications are directly proportional to exposure
      time. Furthermore, our results show that psychological tests commonly used in
      psychopathologic diagnostics can be useful in monitoring alterations of psycho
      emotional status determined by physical stressors.

PMID- 15479994
TI  - Reasons for quitting serotonin reuptake inhibitor therapy: paradoxical
      psychological side effects and patient satisfaction.
AB  - BACKGROUND: The goal of this study was to document the existence of psychological
      side effects associated with serotonin reuptake inhibitors (SSRIs) taken for
      depression and to determine their relationship to patients' decisions to stop
      treatment, and attitudes toward taking SSRIs again. METHOD: We conducted 161 semi
      structured telephone interviews of adults who had completed a course of treatment
      for depression with one of the SSRIs. We identified 29 categories of unwanted
      psychological effects and analyzed data in terms of responders and non
      responders, the former split into those who would, and those who would not take
      the same drug again if depressed in the future ('take-again responders' and 'not
      again responders', respectively). RESULTS: Psychological side effects were cited
      just as often as physical side effects as the primary reason for quitting SSRI
      treatment. Non-responders cited psychological side effects rather than non
      response as the primary reason for quitting, and not-again responders cited
      physical more than psychological side effects. Not-again responders and non
      responders did not differ in the number of side effects experienced, and non
      responders experienced significantly more unwanted psychological effects than
      either type of responder (chi2= 6.767, p=0.009). CONCLUSION: Psychological side
      effects might well be included in measures and discussions of side effects, even
      though they present no known physical danger to the patient.

PMID- 15479995
TI  - Diagnosing ICD-10 depressive episodes: superior criterion validity of the Patient
      Health Questionnaire.
AB  - BACKGROUND: Diagnosing and monitoring depression in primary care remains an issue
      of significant public health concern. Clinicians and researchers need to know if
      any one screening instrument is superior to the others in diagnosing ICD-10
      depressive episodes. This study aimed to examine the criterion validity for
      diagnosing ICD-10 depressive episodes of the Patient Health Questionnaire (PHQ)
      in comparison with 2 well-established instruments, the Hospital Anxiety and
      Depression Scale (HADS), and the WHO Well-Being Index 5 (WBI-5). METHODS: Five
      hundred and one medical outpatients completed the questionnaires and had a
      clinical interview. The presence of a depressive episode was determined with the
      International Diagnostic Checklists (IDCL) for ICD-10 as the criterion standard.
      Coefficient kappa (kappa), sensitivities and specificities were calculated and a
      statistical comparison of the areas under the receiver operating characteristic
      curves was performed. RESULTS: Diagnostic agreement between the questionnaires
      and the IDCL was moderate (kappa=0.34-0.56), with the highest values for the PHQ.
      While all 3 questionnaires had reasonable sensitivity and specificity, the
      operating characteristics for the PHQ were significantly superior to both the
      HADS and the WBI-5 (p=0.02). CONCLUSIONS: Any of the 3 screening instruments can
      be recommended for clinical use. However, this is the first comparative study to
      demonstrate the diagnostic advantage of a particular depression-screening
      instrument using the ICD-10 diagnostic criteria. The superior criterion validity
      of the PHQ is likely attributable to its closer representation of the current
      concept of depressive disorders.

PMID- 15479997
TI  - Current concepts and advances in clinical parallel magnetic resonance imaging.
AB  - Parallel imaging (PI) is one of the most promising recent advances in MRI
      technology and has, similar to the introduction of multidetector helical scanning
      in CT, revolutionized MR imaging. The speed of all conventional MRI methods has
      been limited by either gradient strength or their switching times. The basic idea
      in PI is to use some of the spatial information contained in the individual
      elements of a radiofrequency (RF) receiver coil array to increase imaging speed.
      These PI techniques are removing some of the previous limitations in speed of MRI
      scanners and set the basis for accelerated image formation. Initially, PI was
      motivated by the wish to accelerate image acquisition without reducing the
      spatial resolution of the image. However, depending on the application, it turned
      out that PI harbors several other advantages. Among those is the possibility for
      higher spatial resolution, shorter breath-holds or multiple averaging to diminish
      motion artifacts, reduced image blurring and geometric distortions, better
      temporal resolution, and means for navigator correction. This overview focuses on
      technical aspects, clinical applications, and ongoing research in different areas
      of the human body. The critical review demonstrates PI's great versatility as
      well as the current trends to use this unique technique in the majority of
      clinical scan protocols.

PMID- 15479998
TI  - Reduced data acquisition methods in cardiac imaging.
AB  - In cardiac imaging, acquisition speed is of primary importance. While improved
      performance has mainly been achieved through improvements in gradient hardware in
      the past, further developments along this direction are limited due to
      physiological constraints such as the risk of peripheral nerve stimulation. With
      the introduction of parallel imaging, alternative means for increasing
      acquisition speed have become available. Using information from multiple receiver
      coils, images can be reconstructed from a sparsely sampled set of data. In
      practice, parallel imaging allows for 2- to 3-fold acceleration of the imaging
      process in typical cardiac applications. Further increases in acquisition speed
      are, however, difficult to achieve for current clinical field strengths and
      typical field of views. To address the limited gain in acquisition speed
      achievable with parallel imaging, a new set of methods has been proposed to take
      into account the similarity of image information at different time points during
      a dynamic series. Using these methods, 5- to 8-fold acceleration can be achieved
      in cardiac imaging. It is the purpose of this paper to review cardiac
      applications of reduced data acquisition methods with focus on parallel imaging
      and the recently developed k-t BLAST and k-t SENSE techniques.

PMID- 15479999
TI  - Parallel imaging in MR angiography.
AB  - The recently developed techniques of parallel imaging with phased array coils are
      rapidly becoming accepted for magnetic resonance angiography (MRA) applications.
      This article reviews the various current parallel imaging techniques and their
      application to MRA. The increased scan efficiency provided by parallel imaging
      allows increased temporal or spatial resolution, and reduction of artifacts in
      contrast-enhanced MRA (CE-MRA). Increased temporal resolution in CE-MRA can be
      used to reduce the need for bolus timing and to provide hemodynamic information
      helpful for diagnosis. In addition, increased spatial resolution (or volume
      coverage) can be acquired in a breathhold (eg, in renal CE-MRA), or in otherwise
      limited clinically acceptable scan durations. The increased scan efficiency
      provided by parallel imaging has been successfully applied to CE-MRA as well as
      other MRA techniques such as inflow and phase contrast imaging. The large signal
      to-noise ratio available in many MRA techniques lends these acquisitions to
      increased scan efficiency through parallel imaging.

PMID- 15480000
TI  - Application of SENSE in clinical pediatric body MR imaging.
AB  - Pediatric body magnetic resonance imaging can be challenging because of the
      intrinsic physiologic motions from high respiratory and heart rates. Unlike in
      adults, in preadolescent children, breath holding is often not an available
      option. In this paper, the authors describe their clinical experience using the
      recently available parallel imaging technique, sensitivity encoding (SENSE), to
      improve on the image quality of pediatric body MR examinations. The three major
      areas described include rapid imaging using SENSE to achieve time-resolved
      contrast-enhanced MRA, improvement in single-shot turbo spin echo imaging with
      SENSE, and decreasing respiratory motion artifact with combination of SENSE and
      multiple signal averages in various pulse sequences. Some practical suggestions
      of using SENSE in clinical pediatric body MR examinations are highlighted. The
      addition of SENSE has allowed for improved image quality and more efficient
      overall MR examinations for pediatric body imaging.

PMID- 15480001
TI  - Parallel imaging of the abdomen.
AB  - Parallel imaging holds great potential for improving the quality of diagnostic
      abdominal MRI. The increased imaging speed afforded by parallel imaging can be
      translated into the obvious benefits of reduced scan time with set resolution and
      coverage, improved spatial resolution with set imaging time and coverage,
      increased anatomic coverage for a set imaging time and resolution, or some
      combination of the above. Additionally, the reduction in scan time can also allow
      some sequences that normally require multiple breath-holds to be performed with
      only one, or simply make breath-hold imaging possible for more patients. The
      decreased echo-train length allows for truer T2-weighting, less magnetic
      susceptibility artifact, and less blurring with echo-train imaging. Dynamic
      contrast-enhanced sequences can be acquired with improved temporal or spatial
      resolution. All of these potential advantages come with the trade-off of
      decreased signal-to-noise ratio, but for many patients, the benefits far outweigh
      the drawbacks and can vastly improve the diagnostic quality of abdominal MRI.

PMID- 15480002
TI  - Fast patient workup in acute stroke using parallel imaging.
AB  - Treatment of ischemic stroke is a very frustrating topic for neurologists.
      Presently, the most promising therapy seems to be thrombolysis of the clot.
      However, this intervention is associated with complication risks, most
      significantly the risk of post-treatment hemorrhage. This risk of bleeding
      increases not only with the size of the ischemic brain tissue but also with the
      time-to-treatment interval. Studies suggest a time window of 3 hours for most
      effective treatment. Hence, there is demand for a rapid imaging workup, which
      thus far has been accomplished with computed tomography. Because of the risks
      associated with thrombolytic therapy, more detailed information is desirable. The
      distinction between patients with viable ischemically challenged neural tissue
      and those with complete infarcts is of great importance, and computed tomography
      is insufficient for this task. This is also true for outlining the etiology of
      stroke, which may impact treatment. For these tasks, magnetic resonance imaging
      has been proposed. However, comprehensive imaging protocols take time, which is
      limited in stroke treatment. Therefore, new imaging techniques are required that
      provide both in-depth information and short scanning times. Parallel imaging is
      uniquely suited for this purpose.

PMID- 15480003
TI  - Clinical outcome and patients' satisfaction after simultaneous bilateral breast
      reconstruction with free transverse rectus abdominis muscle (TRAM) flap.
AB  - In the study presented, the long-term outcome and satisfaction of 34 patients who
      underwent simultaneous bilateral breast reconstruction with a free transverse
      rectus abdominis muscle (TRAM) flap between 1988 and 2001 were assessed. Flap
      complications affected 13 of 68 flaps (19.1%). Anastomosis revision was needed in
      6 cases (8.8%), the salvage rate being 50%. The rates of total and partial flap
      loss were 4.4% and 1.5%, respectively. Bilateral flap loss did not occur. Four
      patients developed donor site complications (11.7%), with wound healing problems
      being the most common (5.8%). Most patients were satisfied with their decision to
      have had breast reconstruction with free TRAM, 91% would choose the same
      operation again, and 91% would recommend this procedure to other patients. Of the
      operated patients, 20.8% felt an improvement in their sexual life; more patients,
      however, reported an improvement concerning their social life (37.5%) and life in
      general (50%).

PMID- 15480004
TI  - The "perfusion map" of the unipedicled TRAM flap to reduce postoperative partial
      necrosis.
AB  - The unipedicled transverse rectus abdominis musculocutaneous (TRAM) flap is a
      well-known technique for breast reconstruction. However, it is clinically
      difficult to evaluate the blood perfusion of the flap in the operating room. A
      new technique of blood supply evaluation, employing indocyanine green dye (ICG)
      fluorescence videoangiography has been performed in 10 cases of unipedicled TRAM
      flap breast reconstruction. In our series, the ICG measurement was demonstrated
      to be a safe, quick, and accurate technique of flap perfusion analysis. We
      confirmed the presence of individual pattern ("perfusion map") of the flap
      perfusion, zone II sometimes not being as well perfused as zone III. In this
      paper, we present our descriptive findings, and the ICG analysis seems to have a
      predictive value of unipedicled TRAM flap viability.

PMID- 15480005
TI  - Laparoscopically harvested omental flap for chest wall and intrathoracic
      reconstruction.
AB  - Minimally invasive surgery has gained popularity in the last decade and its
      applications to plastic surgery are expanding. Pedicled omental flaps are used
      for the reconstruction of chest wall defects following debridement of sternal
      infections and mediastinitis. The main advantages of using an omental flap are
      its large size and bulk to fill large 3-dimensional dead spaces, long pedicle,
      and rich vascular and lymphatic networks. Recently, laparoscopic techniques have
      been described for harvesting omental flaps. Over the last 5 years in our
      institution, 9 laparoscopic omental flap harvests were performed. Seven were used
      in the reconstruction of complicated chest wall defects, sternal infections,
      mediastinal abscesses, and mediastinitis following cardiac surgery. Two were used
      to repair intrathoracic viscera. Prior abdominal surgery was not a
      contraindication to the laparoscopic harvest. In 1 patient, the omental transfer
      was converted to a free flap due to the detachment of the pedicle, and in 1
      patient the omental harvest was converted to open technique due to technical
      difficulty due to severe abdominal adhesions. None of the patients had major
      intraabdominal complications postoperatively. One patient had a small
      transdiaphragmatic hernia treated by laparoscopic techniques. The use of
      laparoscopy techniques facilitated the harvesting of the omentum, making it ideal
      in the treatment of complicated patients with multiple comorbidities. With these
      techniques, pedicled omental flaps will be a reasonable treatment option for
      chest wall reconstruction.

PMID- 15480006
TI  - Composite plate and wire fixation for complicated sternal closure.
AB  - Many techniques have been described to achieve closure of complicated median
      sternotomy wounds. The standard method of closure uses stainless steel wiring of
      the sternal halves; however, in complicated sternal closures, sternal cut-through
      and wire failure can occur. Recent literature advocates the use of fixation
      plates that achieve bony union, with plating across the median sternal osteotomy
      site as a singular method. We describe a technique of composite closure using
      titanium fixation plates to buttress the sternum in combination with
      circumferential stainless steel wires. This composite technique has been used in
      6 patients with complicated sternal closures. Successful wound closure without
      complication was achieved in all cases. The technique and the clinical series
      with an illustrative example are presented. The use of plate and wire fixation
      represents an alternate method to conventional techniques to achieve sternal
      closure, stability, and uncomplicated wound healing in these difficult-to-manage
      cases.

PMID- 15480007
TI  - Free tissue transfer to a difficult wound of the lower extremity.
AB  - Amputation is still recommended to patients with a difficult wound of the lower
      extremity because limb salvage after free tissue transfer in these patients
      remains uncertain. During the past 3 years, the authors studied 15 patients (11
      men, 4 women; age range, 17-71 years) with difficult wounds of the lower
      extremities who had free tissue transfers for limb salvage. Eleven patients had
      an extensive soft-tissue defect (nearly the entire length) of the legs or feet,
      and 4 had a composite-tissue defect of the legs or feet that required bony
      reconstruction. A total of 16 free tissue transfers (13 free muscle flaps, 2
      osteomusculocutaneous flaps, and 1 adipofascial flap) were performed in 15
      patients (1 patient had bilateral transfers). A saphenous vein loop or graft was
      used in 3 patients and a subsequent bone graft was done in 2 patients. Free
      tissue transfer was accomplished successfully in 14 patients (93%). Limb salvage
      was achieved ultimately in 12 patients (80%) who were able to ambulate during a
      36-month follow-up. The authors believe that free tissue transfer for limb
      salvage in any patient with a difficult wound of the lower extremity is still a
      worthwhile procedure and should be attempted if possible. Meticulous preoperative
      preparation and intraoperative execution combined with the use of innovative
      microsurgical techniques are the keys for success.

PMID- 15480008
TI  - Adequate venous drainage: the most critical factor for a successful free jejunal
      transfer.
AB  - Reconstruction of the cervical esophagus with free jejunum can yield excellent
      functional results. Flap survival alone, however, does not guarantee satisfying
      functional outcomes. Critical factors that determine the level of function of the
      flap include the duration of ischemia and degree of venous congestion. An attempt
      is made in this study to evaluate the degree that these 2 factors influence
      outcome and to establish safe methods for avoiding suboptimal functional results.
      Out of 71 patients that underwent free jejunal transfer for the reconstruction of
      the cervical esophagus between January 1995 and December 1999, 60 patients with
      available chart records were included into this study. A retrospective chart
      review was performed on all 60 patients to evaluate the degree of venous
      congestion in those patients and the choice of recipient veins and method of
      anastomosis of those veins (end-to-end versus end-to-side). A more detailed
      review was performed on the 8 patients that underwent reexploration and detailed
      history, operative method, ischemia time, choice of recipient vessels, technique
      of anastomosis, immediate postoperative course, and outcome were determined.
      Following exploration of the flaps, all flaps survived. Two developed partial
      necrosis. When smaller veins were used as recipient vessels, the chances of
      venous congestion were found to be higher than when larger recipient veins were
      used (chi2 analysis, P <0.02). Method of anastomosis and previous radiotherapy
      were both found to be significant determinants of venous congestion (chi2 P <0.05
      for both). Venous problems accounted for 87.5% (7/8) of all reexplorations. In
      75% (6/8) of the reexplored patients, pharyngocutaneous fistula formation or
      stricture formation was noted.The degree of venous congestion and previous
      radiotherapy are factors that influence the functional outcome of free jejunal
      flaps. Proper selection of the recipient veins is a critical factor in providing
      adequate venous outflow and minimizing venous congestion. End-to-side anastomosis
      to large vessels is a more reliable method that was found to have a significant
      influence on minimizing venous congestion and is a useful method for the salvage
      of venous congested flaps.

PMID- 15480009
TI  - The use of subcutaneous pedicle rhomboid flap in the treatment of postburn scar
      contractures.
AB  - PURPOSE: To investigate the efficacy and versatility of subcutaneous pedicle
      rhomboid flap in the treatment of linear or wide postburn scar contractures
      located in various parts of the body. MATERIALS AND METHODS: Twenty-three
      patients (aged 5 to 35 years) with postburn linear and wide scar contractures
      were treated with 31 subcutaneous pedicle rhomboid flaps. Rhomboid flaps were
      applied in the trunk (4 flaps), head and neck (5 flaps), lower extremity (5
      flaps), and upper extremity (17 flaps). In 3 cases, Z-plasty was incorporated to
      the technique due to inadequate release. RESULTS: All rhomboid flaps healed
      uneventfully. In 28 contractures, rhomboid flaps alone were efficient to release
      the tension line (90.3%). Tip necrosis of the triangular flaps of Z-plasty in 1
      case was the only complication seen that later led to recontracture. CONCLUSION:
      Clinical results indicated that subcutaneous pedicle rhomboid flap is a simple,
      efficient, and versatile technique in release of any postburn scar contracture.
      As no undermining is carried out, the flaps are more reliable than commonly used
      Z-plasty. Again contrary to Z-plasty, displacement of anatomic landmarks such as
      axillary hair and areola is rare with the technique.

PMID- 15480010
TI  - Split sternocleidomastoid muscle repositioning for correction of depressed post
      tracheostomy scar and tracheal tug.
AB  - One important complication of tracheostomy procedure is the depressed scar left
      after the airway is removed. The problem is more challenging for the surgeon if
      tracheal tug accompanies. Six male patients with unaesthetic, depressed
      tracheostomy scars due to late removal of tracheostomy tubes after maxillofacial
      high-velocity gunshot injuries were treated. The patients' age ranged from 20 to
      23 years, with an average age of 21 years. The mean tracheostomy tube removal
      time was 18 days (range, 9 to 34 days) postoperatively. The mean scar dimension
      was 13.4 mm x 14.4 mm x 4 mm (width, length, and depth, respectively). All
      patients showed tracheal tug and complained of swallowing discomfort. Under local
      anesthesia, split sternocleidomastoid muscle flaps were used bilaterally
      following excision of the skin scars and covered by adjacent skin flaps. The mean
      follow-up was 18 months. Cosmetic and functional results were satisfactory for
      all patients. Dysphagia disappeared in all patients following surgery. This
      technique is useful and easy to perform for reconstruction of complex post
      tracheostomy scars.

PMID- 15480011
TI  - Use of calcium phosphate cement for bone defect after harvesting radial forearm
      osteocutaneous flap.
AB  - To resolve esthetic and psychologic discomfort of patient due to the lack of
      radius after harvesting radial forearm osteocutaneous flap, we filled the bone
      defect and recreated its contour using calcium phosphate cement (CPC; Biopex;
      Mitsubishi Material Corporation, Tokyo, Japan). Injection of CPC was performed in
      5 patients (3 women and 2 men). The patients' age ranged from 61 to 72 years
      (mean, 65 years), and the follow-up period ranged from 8 to 18 months. The size
      of the radius harvested varied from 10 x 35 mm to 10 x 50 mm. The width of the
      harvested bone was approximately 25% to 35% of the circumference of radius.
      Injected CPC volume varied from 3 to 4 mL, approximately. There was no
      postoperative infection or allergic reaction in any patient, and movement of hand
      was also with no problem. The X-P findings showed that the bone defect was filled
      with a uniform, high-density mass. The injected cement reduced in volume
      gradually during the fourth or fifth postoperative months, but the degree of
      reduction was mild in any case, which is probably less than 5% of the injected
      amount, allowing successful recreation of the contour of the radius. We conclude
      that the use of CPC for filling the defect of the bone donor site after
      harvesting radial osteocutaneous flap is valid method to keep a patient free from
      esthetic and psychologic discomfort due to the lack of the radius.

PMID- 15480012
TI  - The medial sural artery perforators: anatomic basis for a surgical plan.
AB  - We performed an anatomic study on 20 fresh lower limbs. Resin was injected in the
      popliteal artery. Medial sural artery perforator flaps were sculptured according
      to anatomic markings. On average, length of flaps was 12.9 cm, width was 7.9 cm;
      all 38 perforators were musculocutaneous: 1 perforator was always found (on
      average, 1.9 per flap). All perforators gathered between 7 and 18 cm from the
      popliteal crease; 34.2% of perforators arose on the midline of the medial head of
      gastrocnemius muscle; before entering the fascia, the perforator artery diameter
      was on average 0.5 mm. Two configurations of the intramuscular course of
      perforators were found. Sixty-six percent of perforators originated from the
      lateral branch of the medial sural artery, 34% from the medial one. These results
      improve the anatomic knowledge of the medial posterior calf region and allow us
      to describe a convenient plan to make flap sculpturing easier.

PMID- 15480013
TI  - Medial plantar arch pinch grafts are an effective technique to resurface palmar
      and plantar wounds.
AB  - Resurfacing the glabrous skin covering the human plantar and palmar surfaces
      constitutes a challenge to the plastic surgeon. Ideally, when this skin is lost,
      it should be replaced by the same type of tissue to provide strength, texture,
      and color match. This paper describes our experience with 9 palmar and plantar
      wounds which were successfully resurfaced with pinch grafts harvested from the
      non-weight-bearing area at the medial plantar arch of the foot. The patients were
      allowed to ambulate after surgery with partial or full weight-bearing as
      tolerated, the donor sites healed in 7 to 9 days without complication, and pinch
      grafts took 100%. The grafted wounds were completely covered with 1 application
      once the grafts reached confluence. Not only was pain eliminated, but the
      patients also were able to ambulate and use their hands with minimal reservation
      2 weeks after surgery. Fourteen-month follow-up examination showed reliable and
      durable results, with perfect tissue match and no contracture. This technique is
      easy to perform in the office under local anesthesia. It is safe and well
      tolerated by the patient.

PMID- 15480014
TI  - Minimal invasive lymphaticovenular anastomosis under local anesthesia for leg
      lymphedema: is it effective for stage III and IV?
AB  - This is the first report on the effectiveness of minimal invasive
      lymphaticovenular anastomosis under local anesthesia for leg lymphedema. Fifty
      two patients (age: 15 to 78 years old; 8 males, 44 females) were treated with
      lymphaticovenular anastomoses under local anesthesia and by postoperative
      compression using elastic stockings. The average duration of edema of these
      patients before treatment was 5.3 +/- 5.0 years. The average number of
      anastomosis in each patient was 2.1 +/- 1.2 (1-5). The patients were followed for
      an average of 14.5 +/- 10.2 months, and the result were considered effective
      (82.5%) even for the patients with stage III (progressive edema with acute
      lymphangitis) and IV (fibrolymphedema), but others showed no improvement. Among
      these cases, 17 patients showed reduction of over 4 cm in the circumference of
      the lower leg. The average decrease in the circumference excluding edema in
      bilateral legs was 41.8 +/- 31.2% of the preoperative excess length. These
      results indicate that minimal invasive lymphaticovenular anastomosis under a
      local anesthesia is valuable instead of general anesthesia.

PMID- 15480015
TI  - Clinical and histologic evaluation of a new injectable implant: hydrophilic
      polyacrylamide gel.
AB  - Hydrophilic polyacrylamide gel is a new, jellylike transparent implant that
      consists of 95% water and 5% polyacrylamide, and it has been applied in many
      countries for many years as a sort of injectable implant. However, there are no
      data regarding human tissue reaction to hydrophilic polyacrylamide gel to date.
      Thirty-one patients who had undergone the injection of hydrophilic polyacrylamide
      gel for soft-tissue augmentation from September 1998 to November 2001 wanted to
      remove the implant. Hematoxylin-eosin-stained sections from each cyst of tissue
      sample were investigated and analyzed with light microscopy. The tissue slices of
      12 patients who had received an injection of silicone from 1988 to 1994 were
      reviewed. The difference in histologic features was assessed. The inflammatory
      reaction of hydrophilic polyacrylamide gel was characterized by the presence of
      more foreign body giant cells. The cellular response ranged from moderate or
      marked (4 to 18 months) to mild (>18 months). The difference was statistically
      significant (P <0.05). Little lymphocyte infiltration was shown in all slices of
      hydrophilic polyacrylamide gel. There were clusters or diffuse lymphocyte
      infiltration on histologic observation of the liquid silicone. The difference was
      significant (P <0.001). In summary, hydrophilic polyacrylamide gel may evoke a
      human tissue inflammatory response similar to other foreign materials. Lumpy
      subcutaneous nodules, mastodynia, and difficult removal may limit its application
      in breast augmentation.

PMID- 15480016
TI  - Propofol improves skin flap survival in a rat model: correlating reduction in
      flap-induced neutrophil activity.
AB  - Accumulation of neutrophils in a random pattern skin flap has been demonstrated
      to contribute to the necrosis of distal flap tissue. This study proposes that
      administration of propofol anesthesia can effectively reduce neutrophil activity
      and enhance skin flap survival. The study was a randomized controlled trial using
      male Sprague-Dawley rats as subjects. For flap survival studies, a 3- by 12-cm,
      dorsal, cranial-based, random pattern skin flap was elevated and reapproximated.
      Flaps were examined for viability 10 days postsurgery. To assess neutrophil
      activity, flap biopsies were taken 12, 24, or 48 hours postsurgery from distal,
      middle, and proximal flap regions, and myeloperoxidase enzyme content was
      analyzed. Animals were randomly assigned to 1 of 4 groups: group 1, ketamine
      anesthesia (controls); group 2, propofol anesthesia; group 3, ketamine anesthesia
      plus 10% lipid emulsion (propofol vehicle); group 4, ketamine anesthesia without
      flap elevation (nonoperated controls for myeloperoxidase study). Flap survival
      was significantly improved in the propofol group compared with both the ketamine
      and vehicle control groups (P <0.01). Increased flap viability was correlated
      with a reduction in myeloperoxidase content in the propofol group compared with
      control operated animals, with minor variations observed in the different flap
      regions and time points tested. This study indicates that the use of propofol can
      potentially improve skin flap survival. The beneficial effects may be attributed
      to a reduction in neutrophil activity within the flap.

PMID- 15480017
TI  - Tracheal reconstruction with a prefabricated deltopectoral flap combined with
      costal cartilage graft and palatal mucosal graft.
AB  - We have created an alternative method for tracheal reconstruction. Our new
      surgical procedure using a deltopectoral flap combined with a costal cartilage
      graft and mucosal graft for tracheal reconstruction allows us to achieve
      reconstruction of the tracheal mucosa, the tracheal cartilage, and the covering
      skin with adequate subcutaneous tissue. In one case, a tracheostenosis was
      reconstructed with a deltopectoral flap combined with a costal cartilage graft.
      In the other case, a tracheal defect was reconstructed with a deltopectoral flap
      combined with a costal cartilage graft and palatal mucosal graft. Although the
      operation is a multistage procedure, our method provides satisfactory clinical
      results. Thus, we believe that our method is useful for the surgical treatment of
      large tracheal defects.

PMID- 15480018
TI  - Microtia reconstruction with adjuvant 3-dimensional template model.
AB  - For auricular reconstruction of external auricle, the goals of the surgery are
      (1) in the fabrication of the morphologically complete 3-dimensional costal
      cartilage framework (3-dimensional frame) of the auricle, and (2) in the
      attainment of ample skin surface area to cover the grafted 3-dimensional frame,
      so that more than satisfactory results can be achieved. In review of the
      published literature, the cartilage framework used for auricular reconstruction
      is either insufficient or incomplete in the fabrication of the anatomic
      structures or inappropriate in proportion. We herein introduce the 3-dimensional
      resin template model (3-dimensional template model) and 3-dimensional frame used
      in our daily surgical practice. The 3-dimensional template model is
      proportionally fabricated with all the essential morphologic structures of the
      auricle. It can be used intraoperatively for reference in fabricating the 3
      dimensional frame and simulation of the surgery. The 3-dimensional template model
      is very useful as an adjuvant tool in adjusting the skin flaps, prevention of
      mistake in fabrication of the 3-dimensional frame, and for educational purposes
      of junior resident surgeons.

PMID- 15480019
TI  - Sinking skin flap syndrome: a case of improved cerebral blood flow after
      cranioplasty.
AB  - Sinking skin flap syndrome is defined as a series of neurologic symptoms with the
      skin depression at the site of cranial defect, which develop several weeks to
      months after large external cerebral decompression.The case of a 28-year-old
      female with the sinking skin flap syndrome is reported together with the
      evaluation of cerebral blood flow using xenon computed tomography (CT). Although
      her general condition stabilized within 7 months after the injury, the skin of
      the bilateral temporal regions was markedly depressed due to large bone defects.
      She was confined to bed and showed reduced levels of consciousness. We decided to
      treat this case by performing cranioplasty with a hydroxyapatite ceramic implant.
      Not only were good cranial contour reconstructed after cranioplasty, but
      neurologic conditions were also improved after cranioplasty. Regarding the change
      in cerebral blood flow in the present case, as measured with xenon CT, the
      cerebral blood flow 3 days after the injury was 18.7 +/- 12.3 mL/100 mL/min and
      26.5 +/- 11.6 mL/100 mL/min in the left and right hemispheres, respectively.
      After the bilateral cranioplasty, it had increased by approximately 2-fold to
      36.4 +/- 23.2 mL/100 mL/min in the left hemisphere and approximately 1.5-fold to
      43.8 +/- 23.3 mL/100 mL/min in the right hemisphere as compared with the levels
      obtained 3 days after the injury.Therefore, xenon CT appears to be useful in the
      monitoring of regional cerebral blood flow in patients with cranial bone defects
      that are directly affected by atmospheric pressure and in predicting functional
      prognosis. For the sinking skin flap syndrome cases, cranioplasty is not only
      useful for cerebral protection and improvement of appearance, but cranioplasty is
      also useful for improving neurologic symptoms.

PMID- 15480020
TI  - Correction of the inverted nipple with an internal 5-point star suture.
AB  - To date, many of the methods reported for the surgical treatment of the inverted
      nipple include insertion of autologous or heterologous material to provide volume
      and projection to the nipple, thereby avoiding recurrence. In cases of severely
      inverted nipple with severe fibrosis and shortening of the lactiferous ducts, the
      authors' technique combines the pulling out of the nipple and the release of the
      fibrosis and retracting ducts with the introduction of a stitch of polyglactin as
      filling material, performing an internal star suture in only one surgical
      intervention, without the need for using graft material, or local flaps that
      introduce scars around the nipple. The technique is simple, with excellent and
      long-lasting results.

PMID- 15480021
TI  - The Gold(wyn) standard.

PMID- 15480022
TI  - Y-shaped vein grafting to Stensen duct defect.

PMID- 15480024
TI  - The reversed dermis flap in a homodigital or cross finger manner for soft tissue
      reconstruction in dorsal finger defects.

PMID- 15480025
TI  - Yet another use for the VAC machine.

PMID- 15480026
TI  - Consequences of radiation accidents.

PMID- 15480028
TI  - Surgical management of the hand in Freeman-Sheldon Syndrome.

PMID- 15480029
TI  - Computed tomography urography with 16-channel multidetector computed tomography:
      a pictorial review.
AB  - Excretory phase computed tomography (CT) urography obtained with a 16-slice
      multidetector CT scanner using thin-section images (slice thickness = 0.75 mm,
      reconstruction increment = 0.5 mm) combined with interactive reformatted and 3
      dimensional reconstruction techniques, high spatial resolution images of the
      urinary tract similar to those of classic intravenous urography can be produced.
      The purpose of this pictorial essay is to review the early experience of the
      authors and to show the wide range of abnormalities of the urinary tract detected
      with this technique.

PMID- 15480030
TI  - Masses and pseudomasses of the kidney: imaging spectrum on MR.
AB  - MR imaging is useful in differentiating and characterizing renal masses. A
      careful evaluation of the signal characteristics and morphology of a renal mass
      combined with the ancillary imaging findings and patient history should assist
      the radiologist in making the proper diagnosis or recommending the appropriate
      treatment in most cases. This pictorial essay demonstrates the typical MR imaging
      features of common renal masses including renal cell carcinoma (RCC), oncocytoma,
      angiomyolipoma, metastases, transitional cell carcinoma (TCC), lymphoma, and
      arteriovenous malformation (AVM), and highlights several potential diagnostic
      pitfalls in making the proper diagnosis.

PMID- 15480031
TI  - Imaging of gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms
      of the gastrointestinal tract and are defined by their expression of KIT (CD117).
      This article includes 109 pathologically proven GISTs, with emphasis on their
      various computed tomography (CT) features. Although the images of GISTs on the CT
      scan are often distinct from those of epithelial tumors, radiologists should be
      familiar with these features for the accurate diagnosis of GISTs.

PMID- 15480032
TI  - Concurrent focal hepatic and splenic lesions: a pictorial guide to differential
      diagnosis.
AB  - Although medical literature and differential diagnoses discussions tend to be
      organ specific, systemic diseases more commonly manifest with multi-organ
      involvement. Detection of dual organ involvement combined with clinical history
      narrows the differential to provide a more specific diagnosis. Two organs closely
      linked are the liver and the spleen. Many processes affect both of these organs
      through their common denominator, the reticuloendothelial system (RES). This
      pictorial essay reviews the wide spectrum of benign and malignant pathologies to
      be considered when computed tomography (CT) demonstrates concurrent focal disease
      in the liver and spleen.

PMID- 15480033
TI  - Magnetic resonance cholangiography with mangafodipir trisodium (Teslascan) to
      evaluate bile duct leaks after T-tube removal in liver transplantation.
AB  - Liver transplant patients who present with abdominal pain after removal of the T
      tube can be initially evaluated by contrast-enhanced magnetic resonance
      cholangiography (CEMRC) instead of abdominal computed tomography and
      hepatobiliary scintigraphy. In this article, 3 liver transplant patients who were
      evaluated by CEMRC after removal of the T-tube. CEMRC successfully identified the
      presence, location and extent of bile duct leaks, and can be performed as a
      diagnostic study in patients with suspected bile duct leaks.

PMID- 15480034
TI  - Primary peritoneal clear cell carcinoma.
AB  - The computed tomography (CT) and magnetic resonance imaging findings of primary
      peritoneal clear cell carcinoma in a 53-year-old woman are reported. A CT scan
      showed a complex cystic mass with solid components that involved the right upper
      quadrant and displaced the liver and the right kidney. Magnetic resonance imaging
      revealed a multicystic mass with hemorrhage and heterogeneous solid protrusions.
      The diagnosis of primary peritoneal clear cell carcinoma was made by
      histopathologic study of the surgical specimen.

PMID- 15480035
TI  - Preoperative magnetic resonance imaging staging of uterine cervical carcinoma:
      results of prospective study.
AB  - OBJECTIVE: To determine the accuracy of the preoperative staging of uterine
      cervical cancer by magnetic resonance (MR) imaging in 115 patients in a
      prospective study. METHODS: A prospective study was performed in 115 patients who
      underwent MR imaging at 1.5 T before surgery or biopsy. Histopathologic findings
      were correlated with MR imaging results for all patients. RESULTS: The accuracy
      of preoperative tumor staging by MR imaging in the 115 patients was 77%. In terms
      of the evaluation of parametrial status, this study had an accuracy of 94% and a
      sensitivity of 38%. The accuracy and sensitivity of MR imaging for vaginal
      invasion were 81% and 87%, respectively. In terms of lymph node metastasis, this
      study had an accuracy of 97% and a sensitivity of 36%. CONCLUSION: Magnetic
      resonance imaging has high accuracy in the preoperative staging of uterine
      cervical cancer.

PMID- 15480036
TI  - Comparison of test-injection method and fixed-time method for depiction of
      hepatocellular carcinoma using dynamic steady-state free precession magnetic
      resonance imaging.
AB  - OBJECTIVE: The purpose of this study was to clarify the usefulness of the test
      injection method as compared with the fixed-time method in dynamic magnetic
      resonance (MR) imaging of hepatocellular carcinoma (HCC). METHODS: Ninety-seven
      patients with a total of 118 hepatocellular carcinomas underwent 3-dimensional
      fast imaging with steady-state free precession (3D-FISP) for dynamic study of the
      liver as well as catheter-assisted computed tomography hepatic angiography (CTHA)
      for preoperative evaluation. In 42 cases, the fixed-time method (30-second scan
      time delay in the hepatic arterial phase [HAP]) was performed (group 1), and in
      55 cases, the test-injection method was performed (group 2). The following
      parameters were evaluated: 1) the adequacy of the HAP, 2) tumor vascularity using
      CTHA findings as a gold standard, and 3) the contrast-to-noise ratio (CNR) of the
      HCC during the HAP of dynamic MR imaging. RESULTS: In group 1, 79% (33 of 42) of
      the cases were obtained at the optimal HAP; the percentage in group 2 was 98% (54
      of 55) of the cases. This difference was statistically significant (P < 0.05).
      The vascularity of 82% of the tumors in group 1 and 89% of those in group 2 was
      diagnosed correctly. Regarding hypervascular tumors, correct evaluation of tumor
      vascularity was made in 87% of group 1 cases and 95% of group 2 cases. No
      significant difference was present between the 2 groups (total: P = 0.43,
      hypervascular HCC: P = 0.29). 3) The CNR calculated for all HCCs in group 2 (mean
      +/- SD: 8.66 +/- 11.0) was significantly higher than that for HCCs in group 1
      (4.29 +/- 9.44; P < 0.05). As for the hypervascular tumors, the CNR calculated
      for group 2 (mean +/- SD: 9.89 +/- 10.6) was also significantly higher than that
      for group 1 (5.52 +/- 9.81; P < 0.05). CONCLUSION: The 3D-FISP dynamic MR imaging
      using the test-injection method resulted in better demonstration of HCC than the
      3D-FISP using the fixed-time method.

PMID- 15480037
TI  - Imaging findings in idiopathic granulomatous mastitis. A review with emphasis on
      magnetic resonance imaging.
AB  - OBJECTIVE: To describe magnetic resonance (MR) imaging features of patients with
      a histologic diagnosis of idiopathic granulomatous mastitis (IGM). METHODS:
      Dynamic contrast-enhanced MR imaging was performed with a 1.5-T MR unit.
      Postprocessing of images included subtraction and calculation of time-intensity
      curves of the enhancing regions at several points in all patients. RESULTS: In
      addition to granulomatous inflammation, biopsy slides of 5 patients demonstrated
      abscess formation without a specific organism (aseptic abscess). One patient had
      a fibrotic tissue component. Magnetic resonance imaging findings were
      heterogeneously enhancing areas with (n = 5) and without (n = 1) multiple ring
      like enhanced abscesses and a circumscribed lesion with heterogeneous contrast
      enhancement (n = 1). Time-intensity curves showed a benign pattern in all but 1
      patient. CONCLUSION: Idiopathic granulomatous mastitis has a number of
      appearances on MR imaging. Magnetic resonance imaging with measurement of time
      signal intensity curves may support the findings of ultrasonography and
      mammography in distinguishing benign inflammatory breast disorders from malignant
      ones; however, biopsy still remains the only method of definite diagnosis.

PMID- 15480038
TI  - Dynamic breast magnetic resonance imaging. Effect of changing the region of
      interest on early enhancement using 2D and 3D techniques.
AB  - OBJECTIVE: To assess the effect of changing the region of interest (ROI) on early
      enhancement (EE) in dynamic breast magnetic resonance (MR) imaging. METHODS: We
      evaluated retrospectively 102 breast lesions: 54 lesions (33 malignancies and 21
      benignancies) studied with 2D and 48 lesions (30 and 18, respectively) with 3D
      gradient-echo dynamic technique (contrast dose 0.1 mmol/kg). Each lesion was
      postprocessed using 3 different regions of interest (ROIs): small circular ROI on
      maximal enhancement (SCR); large circular ROI within the lesion (LCR); and
      irregular ROI by manual contouring (IRR). EE was classified as benign (< or =
      50%), uncertain (51-89%), or malignant (> or = 90%). RESULTS: With 2D, the
      uncertain EEs were 17% for both SCR and LCR, 33% for IRR (P = 0.008); with 3D,
      the uncertain EEs were 4%, 15%, and 13%, respectively (SCR versus LCR, P =
      0.063). More uncertain EEs were obtained with 2D (17-33%) than with 3D (4-15%),
      significantly for SCR (P = 0.043) and IRR (P = 0.013). Considering uncertain EEs
      as positive, sensitivity was 100% for SCR, 91% for LCR, and 82% for IRR (SCR
      versus IRR, P = 0.031) with 2D, 100%, 97%, and 87%, respectively, with 3D
      technique, without significant differences; specificity ranged from 71% to 90%
      with 2D and 61% to 83% with 3D, without significant differences. CONCLUSION: The
      type of ROI influences the EE in dynamic breast MR. Using 3D technique with small
      ROI located on the area of maximal enhancement gives the best results in terms of
      certainty of the level of EE together with top levels of sensitivity.

PMID- 15480039
TI  - Pitfalls of the lactating breast on computed tomography.
AB  - Breasts are usually only incidentally included in computed tomography (CT) scans
      of the abdomen and chest in spite of the fact that pathologic findings are not
      rare. Because postpartum women are normally healthy, they rarely require
      examination; therefore, the presentation of lactating breasts on a CT scan is
      poorly known. The most common postpartum breast feature is engorgement, which is
      characterized by painful swelling associated with a sudden increase in milk
      volume, lymphatic and vascular congestion, and interstitial edema. Its appearance
      on a CT scan does not seem to have been described in the literature to date. The
      CT picture of a lactating breast shows the enlarged gland with bilateral cord-
      and mass-like hyperattenuated tissue. After abrupt cessation of breast-feeding,
      the edema component supervenes and breast tissue may become hypoattenuated. In
      such cases, further ultrasound evaluation is needed. We present 3 cases of
      postpartum breast engorgement as seen on CT.

PMID- 15480040
TI  - Hyperacute extensive middle cerebral artery territory infarcts. Role of computed
      tomography in predicting outcome.
AB  - OBJECTIVE: To assess the prognostic value of computed tomography (CT) in
      hyperacute middle cerebral artery (MCA) infarcts. METHODS: The CT features, total
      CT score, and National Institutes of Health Stroke Scale (NIHSS) score were
      correlated with the 30-day mortality in 16 patients with a hyperacute MCA
      infarct. RESULTS: Admission NIHSS scores were significantly lower in the survival
      group (P = 0.016). The extent of infarct, attenuation of corticomedullary
      differentiation, and total CT score were associated with 30-day mortality (P <
      0.05). In prediction of mortality, extent of an infarct > 67% gave sensitivity,
      specificity, positive predictive value, and negative predictive value rates of
      86%, 100%, 100%, and 90%, respectively. Attenuation of corticomedullary
      differentiation gave sensitivity, specificity, positive predictive value, and
      negative predictive value rates of 86%, 89%, 86%, and 89%, respectively. An NIHSS
      score > 28 gave sensitivity, specificity, positive predictive value, and negative
      predictive value rates of 86%, 67%, 67%, and 86%, respectively. A CT score > 4
      gave sensitivity, specificity, positive predictive value, and negative predictive
      value rates of 86%, 78%, 75%, and 88%, respectively. CONCLUSIONS: Computed
      tomography features and the admission NIHSS score are important predictors of
      survival in hyperacute extensive MCA infarcts.

PMID- 15480041
TI  - Periodically rotated overlapping parallel lines with enhanced reconstruction
      based diffusion tensor imaging. Comparison with echo planar imaging-based
      diffusion tensor imaging.
AB  - OBJECTIVE: To evaluate diffusion tensor imaging (DTI) based on periodically
      rotated overlapping parallel lines with enhanced reconstruction (PROPELLER)
      compared with DTI based on single-shot echo planar imaging (EPI). METHODS:
      Diffusion tensor data were acquired with PROPELLER (PROPELLER-DTI, 3 NEX), EPI
      (EPI-DTI2, 16 NEX) with the same acquisition time (11.4 minutes) and with EPI
      (EPI-DTI1, number of excitations = 4) with a shorter acquisition time (2.8
      minutes). Regions of interest were set in the genu and splenium of the corpus
      callosum, as determined on T2-weighted fast spin echo images and fractional
      anisotropy (FA) maps, separately. Two neuroradiologists visually evaluated image
      distortion and quality in the supra- and infratentorial structures. RESULTS: In
      the genu, standard deviation determined by respective FA maps was decreased in
      order of PROPELLER-DTI, EPI-DTI1, and EPI-DTI2. Both EPI-DTI sequences were
      quantitatively superior in the splenium, but PROPELLER-DTI was less distorted.
      CONCLUSION: Periodically rotated overlapping parallel lines with enhanced
      reconstruction-DTI could become a complementary tool when qualitatively
      evaluating seriously distorted structures.

PMID- 15480042
TI  - Three-dimensional visualization of the nasal cavity and paranasal sinuses.
      Clinical results of a standardized approach using multislice helical computed
      tomography.
AB  - OBJECTIVE: The aim of this study was to introduce 3-dimensional (3D)
      visualization of the nasal cavity and paranasal sinuses as a diagnostic tool and
      to examination the clinical results of its standardized application. METHODS: One
      hundred sixty patients with chronic or acute nasal symptoms underwent helical
      computed tomography scanning and fiberoptic endoscopy of the sinuses, and 120 of
      them underwent endoscopic sinus surgery. The 3D images were compared with the
      axial and multiplanar reconstructed images using a checklist comprising important
      anatomic landmarks. After qualitative assessment of the representation of
      anatomic structures in healthy subjects, the method was applied to pathologic
      cases. The 3D images of these patients were correlated with the preoperative and
      intraoperative findings. RESULTS: Six hundred virtual endoscopies (VEs) were
      performed. The VE views allowed a realistic illustration of the various
      pathologic findings, except from cases with highly obstructive sinonasal disease.
      The correlation between the preoperative fiberoptic endoscopy and the
      intraoperative findings was significant (r = 0.83, P = 0.001). CONCLUSION: The
      standardized clinical application of this method serves as an important
      supplement to 2-dimensional slices and conventional endoscopy.

PMID- 15480043
TI  - Primary peripheral T-cell lymphoma of the face other than mycosis fungoides.
      Computed tomography and magnetic resonance findings.
AB  - OBJECTIVE: To describe the radiologic findings of primary peripheral T-cell
      lymphoma (PTCL) of the face other than mycosis fungoides. METHODS: Computed
      tomography (CT) and magnetic resonance imaging (MRI) findings of 5 consecutive
      patients with pathologically proven primary facial PTCL other than mycosis
      fungoides were retrospectively evaluated. Patients with PTCL involving the
      sinonasal cavity or lymph nodes were excluded. RESULTS: Diagnoses of patients
      included in this study consisted of natural killer/T-cell lymphoma (n = 2),
      subcutaneous panniculitis-like T-cell lymphoma (n = 1), anaplastic large cell
      lymphoma (n = 1), and PTCL not otherwise specified (n = 1). Infiltration or
      swelling of the superficial space of the face was noted on both CT and MRI,
      mimicking inflammation or infection. Also seen were well-enhancing small nodular
      (n = 2) or infiltrative mass-like lesions (n = 2) within the areas of
      infiltration, which showed intermediate signal intensity on T2-weighted images.
      One patient demonstrated infiltration and swelling alone. CONCLUSIONS: Primary
      facial PTCL is a rarely encountered tumor and demonstrates infiltration or
      swelling mimicking inflammation or infection. Nodular or infiltrative mass-like
      lesions may be helpful for its diagnosis.

PMID- 15480044
TI  - Septal bounce in constrictive pericarditis. Diagnosis and dynamic evaluation with
      multidetector CT.
AB  - Sixteen-slice multidetector CT findings of a case of constrictive pericarditis in
      a pediatric patient are presented. Multidetector CT depicted a variety of
      diagnostic findings including dynamic evaluation of interventricular septal
      motion through the cardiac cycle, documenting a diastolic septal bounce. This
      case illustrates the full capabilities of multidetector cardiac CT in the
      evaluation of pericardial pathology.

PMID- 15480045
TI  - Comparison of electron beam computed tomography with magnetic resonance imaging
      in assessment of right ventricular volumes and function.
AB  - OBJECTIVE: Intraindividual comparison of right ventricular volumes and function
      using electron beam computed tomography (EBT) and magnetic resonance imaging
      (MRI). METHODS: Twenty-seven patients with a known cardiac history were referred
      for evaluation of ventricular function parameters. The following standardized
      protocols were used: contrast-enhanced multislice mode EBT and gradient echo
      sequence MRI. Right ventricular end-diastolic volume (EDV), end-systolic volume
      (ESV), stroke volume (SV), and ejection fraction (EF) were calculated using a
      slice summation method. Interobserver variability was calculated. RESULTS: The
      correlation between the 2 methods was: r = 0.901 for EDV, r = 0.938 for ESV, r =
      0.823 for SV, and r = 0.953 for EF. Electron beam computed tomography
      overestimated EDV and ESV slightly when compared with MRI (P < 0.05). No
      significant differences (P > 0.05) were found between SV and EF. Mean values
      determined by EBT and MRI were as follows: 168.6 +/- 62.3 mL and 153.7 +/- 59.1
      mL for EDV, 104.7 +/- 60.4 mL and 95.1 +/- 54.8 mL for ESV, 63.2 +/- 19.3 mL and
      58.7 +/- 19.8 mL for SV, and 40.2% +/- 14.1% and 40.2% +/- 13.6% for EF,
      respectively. Interobserver variability ranged between 1.0% and 3.2%. CONCLUSION:
      Electron beam computed tomography shows good agreement with a close correlation
      and an acceptable interobserver variability for right ventricular volumes and
      global function, with a small but significant overestimation of EDV and ESV when
      compared with MRI.

PMID- 15480046
TI  - Acute respiratory distress syndrome. Computed tomography findings and their
      applications to mechanical ventilation therapy.
AB  - In acute respiratory distress syndrome, computed tomography (CT) typically
      demonstrates symmetric ground-glass opacity and gravity-dependent consolidation
      when patients are positioned supine. Moreover, CT findings may vary according to
      the evolutional stage of the disease over time. The slope of the pressure-volume
      curve, which is a direct or indirect measure of lung recruitment rather than a
      measure of the characteristics of the respiratory mechanics of a portion of the
      aerated lung, indicates the potential for recruitment. The lung recruitment
      maneuver is performed by maintaining a sustained increase in airway pressure with
      the goal of opening collapsed alveoli, after which sufficient positive end
      expiratory pressure is applied to maintain the alveoli in an open state. Alveolar
      recruitment resulting from continuous positive airway pressure occurs
      predominantly in nondependent and cephalic lung regions and is more limited in
      the diaphragmatic region or even negative (alveolar derecruitment) caudal to the
      diaphragmatic cupola. By partially relieving cardiac and abdominal compression,
      positioning patients in prone and semirecumbent positions may reopen dependent
      and caudal lung regions and improve gas exchange. The mean CT attenuation of a
      given region is equivalent to its aeration. Computed tomography, especially
      helical CT, may help to assess alveolar recruitment and lung overinflation by
      providing information on whole-lung attenuation.

PMID- 15480047
TI  - Esophageal magnetic resonance fluoroscopy: optimization of the sequence.
AB  - OBJECTIVE: The purpose of this study was to try to delineate the esophageal
      passage under dynamic conditions and to determine optimum settings for esophageal
      magnetic resonance (MR) imaging. METHODS: Ten healthy volunteers underwent MR
      fluoroscopy with two T1-weighted sequences: turbo field echo (TFE) and T1
      weighted fast field echo (T1-FFE). These sequences were compared for signal-to
      noise ratios (SNRs) and image quality. To determine the optimum slice thickness,
      an additional 10 healthy volunteers underwent MR fluoroscopy. Results obtained
      for slice thicknesses of 25, 35, 45, and 55 mm were compared for delineated
      length of the esophagus and image quality. RESULTS: The T1-FFE sequences provided
      higher SNRs and better image quality than the TFE sequences (T1-FFE: 89.4 +/-
      28.0, TFE: 52.4 +/- 16.7; P < 0.001). Artifacts were less prominent and
      delineation of the esophageal wall was better on the T1-FFE images. The
      delineation of the esophageal wall was best with a 35-mm slice thickness,
      although delineated length was the longest with a 55-mm slice thickness.
      CONCLUSION: This study showed T1-FFE to be a more suitable sequence than TFE and
      that the 35-mm slice thickness was the optimum slice thickness for esophageal MR
      fluoroscopy.

PMID- 15480048
TI  - High incidence of chest malignancy detected by FDG PET in patients suspected of
      recurrent squamous cell carcinoma of the upper aerodigestive tract.
AB  - OBJECTIVE: To determine the incidence of chest neoplasms detected by FDG PET in
      patients with previously treated squamous cell head and neck cancer (HNC), being
      evaluated for possible recurrent disease. METHODS: This is a retrospective review
      of 41 patients (M = 29, F = 12: average age = 58 years) with previously treated
      HNC who underwent FDG PET of the neck and chest as part of routine evaluation for
      locoregional and/or distant recurrence. Thirty-four of 41 patients had advanced
      stage III or IV HNC. All FDG PET studies were reviewed by dedicated nuclear
      medicine physicians, including evaluation for abnormal uptake in the chest. The
      chest FDG findings were correlated with serial chest radiographs or chest CT. The
      occurrence rate of incidental chest malignancy was determined and based on
      characteristic imaging findings, biopsy, and/or clinical course. RESULTS: Twelve
      of 41 patients had abnormal FDG uptake in the lungs and/or mediastinum. Ten of 12
      patients were found to have neoplasms that could represent either metastases or a
      new lung primary. Five of these 10 were unsuspected neoplasms prior to FDG PET.
      The other 2/12 FDG PET scans in the chest were false positive. There was one
      false-negative FDG PET, with subsequent PET and CT demonstrating pulmonary
      metastases. Overall, there was a 27% incidence of chest malignancies in patients
      with advanced HNC being evaluated for possible recurrence. CONCLUSION: Our study
      demonstrated a chest malignancy in 1 out of 4 patients with advanced HNC being
      evaluated for locoregional and/or distant spread. Fifty percent were unsuspected
      prior to FDG PET. This result suggests that FDG PET of the lungs should be
      routinely included in the evaluation of high-risk patients.

PMID- 15480049
TI  - Thoracic manifestation of myeloperoxidase-antineutrophil cytoplasmic antibody
      (MPO-ANCA)-related disease. CT findings in 51 patients.
AB  - OBJECTIVE: To assess the pulmonary CT findings of patients with serum evidence of
      the myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). METHODS: The
      pulmonary CT scans of 62 patients with serum evidence of MPO-ANCA (51 with
      microscopic polyangiitis, 11 with Churg-Strauss syndrome) were retrospectively
      assessed with regard to parenchymal, pleural, and mediastinal abnormalities.
      RESULTS: On the CT scans, abnormal findings were seen in 51 of the patients (82%,
      n = 62). Of the patients, the CT findings consisted of ground-glass attenuation
      in 48 of the patients (94%, n = 51), consolidation in 40 (78%), and thickening of
      bronchovascular bundles in 26 (51%). Pathologically, these findings corresponded
      to alveolar hemorrhages, interstitial chronic inflammation in the alveolar septa,
      vasculitis, or fibrosis. These abnormalities were predominantly seen in
      peripheral lung parenchyma (n = 37). CONCLUSION: The CT findings in patients with
      MPO-ANCA consisted mainly of ground-glass attenuation and consolidation in the
      peripheral lung. These findings, although nonspecific, are considered as
      pulmonary involvement in patients with MPO-ANCA.

PMID- 15480050
TI  - Bronchobiliary fistula after liver transplantation.
AB  - This report describes the imaging findings of the first reported case of a
      bronchobiliary fistula that developed as a complication of liver transplantation.
      The diagnosis was confirmed by the aspiration of bile from the bronchus.

PMID- 15480052
TI  - Biology of developmental and regenerative skeletogenesis.
AB  - Embryonic skeletal development involves the recruitment, commitment,
      differentiation, and maturation of mesenchymal cells into those in the skeletal
      tissue lineage, specifically cartilage and bone along the intramembranous and
      endochondral ossification pathways. The exquisite control of skeletal development
      is regulated at the level of gene transcription, cellular signaling, cell-cell
      and cell-matrix interactions, as well as systemic modulation. Mediators include
      transcription factors, growth factors, cytokines, metabolites, hormones, and
      environmentally derived influences. Understanding the mechanisms underlying
      developmental skeletogenesis is crucial to harnessing the inherent regenerative
      potential of skeletal tissues for wound healing and repair, as well as for
      functional skeletal tissue engineering. In this review, a number of key issues
      are discussed concerning the current and future challenges of the scientific
      investigation of developmental skeletogenesis in the embryo, specifically limb
      cartilage development, and how these challenges relate to regenerative or
      reparative skeletogenesis in the adult. Specifically, a more complete
      understanding the biology of skeletogenic progenitor cells and the cellular and
      molecular mechanisms governing tissue patterning and morphogenesis should greatly
      facilitate the development of regenerative approaches to cartilage repair.

PMID- 15480053
TI  - Collagens and cartilage matrix homeostasis.
AB  - At least 27 types of collagen, the products of forty genes, are expressed in the
      tissues of higher vertebrates. Cartilage has a distinctive collagen phenotype.
      Two-thirds of the dry weight of adult articular cartilage is collagen.
      Proteolysis of this collagen framework is integral to the process of cartilage
      destruction and joint failure in osteoarthritis. Molecular studies are revealing
      the mechanisms of assembly of cartilage collagen fibrils. The nascent Type II
      collagen fibril is a heteropolymer, with collagen IX molecules covalently linked
      to the surface and collagen XI forming a filamentous template at the core, which
      regulates fibril diameter through its retained N-propeptide domains. This
      structure presents a challenge to understanding how fibril growth and collagen
      network maturation are brought about. Proteolytic remodeling, other than that
      mediated by collagenases, would appear to be involved, but the proteases and
      molecular mechanisms are still undefined. Valuable insights and predictions on
      the function of the individual collagen types in cartilage continue to come from
      the study of skeletal dysplasia syndromes caused by mutations in genes for
      collagens and associated matrix proteins.

PMID- 15480054
TI  - Extracellular matrix gene regulation.
AB  - Extracellular matrix metabolism plays a central role in development of skeletal
      tissues and in most orthopaedic diseases and trauma such as fracture or osteotomy
      repair, arthritis, cartilage repair, and congenital skeletal deformity. During
      development or disease, specific genes must be expressed in order to make or
      repair appropriate extracellular matrix. For example, specific gene expression
      patterns are characteristic of bone and cartilage. The precise expression pattern
      depends on a balance of positive and negative transcription factors, proteins
      that control the synthesis of mRNA from the specific gene. In cartilage, a number
      of studies indicate that Sox transcription factors are critical positive
      regulators in genes such as COL2A1, COL9A2, COL11A2, aggrecan, and CD-RAP. In
      addition, negative regulators are also essential to fine tune gene regulation in
      chondrocytes and to turn off gene expression in noncartilaginous tissues.
      Negative transcription factors in cartilage include partial differentialEF-1,
      snail/slug, CYRBP1, NT2, and C/EBP. Runx2 and osterix are critical transcription
      factors for osteogenesis but also have some influence on chondrogenesis. The
      availability of cis-regulatory sites in specific genes combined with the
      availability of transcription factors in the nucleus determines the level of gene
      expression.

PMID- 15480055
TI  - Novel inhibitors of matrix metalloproteinase gene expression as potential
      therapies for arthritis.
AB  - Matrix metalloproteinases are a family of endopeptidases that collectively
      degrade all components of the extracellular matrix at neutral pH. During the
      progression of arthritis, MMPs mediate the degradation of cartilage, which
      consists largely of Type II collagen fibrils and proteoglycans. The collagenases,
      a subgroup of MMPs, have the singular ability to cleave intact collagens and may
      provide a rate-limiting step in cartilage destruction. In arthritic lesions,
      collagenase-1 (matrix metalloproteinase-1) and collagenase-3 (matrix
      metalloproteinase-13) mediate the irreversible destruction of cartilage,
      suggesting that these enzymes are therapeutic targets. We describe the role of
      metalloproteinases in the destruction of connective tissues in arthritis and the
      treatment strategies that have been developed to block matrix metalloproteinases
      in an attempt to prevent this destruction. We also discuss novel compounds that
      may selectively inhibit these cartilage-degrading enzymes, providing
      opportunities to develop new therapeutic approaches.

PMID- 15480056
TI  - Functional genomics of osteoarthritis: on the way to evaluate disease hypotheses.
AB  - Functional genomics is a challenging new way to address complex diseases such as
      osteoarthritis on a molecular level. This complements previous research and will
      open up new areas of so far unrecognized molecular networks. In this respect,
      articular cartilage is a good target for functional genomics as it contains only
      one cell type to which all expression signals can be attributed to. Despite
      considerable limitations at present, such as a low sensitivity and insensitivity
      to alternative splicing, posttranscriptional regulation, and posttranslational
      modification, cDNA-array technology provides a powerful tool to obtain an
      overview on gene expression patterns hardly achievable with other techniques.
      This has been shown to be true for known genes as well as for the identification
      of new genes of interest. Therefore, gene expression analysis will help to
      identify single genes depending on the disease and experimental conditions
      investigated. However, the expression pattern of the plethora of expressed genes
      will paint a picture (network) of disease context, maybe even more pushing
      forward our understanding of complex diseases such as osteoarthritis.

PMID- 15480058
TI  - Protein kinases in chondrocyte signaling and osteoarthritis.
AB  - Protein kinases, particularly mitogen-activated protein kinases and receptor
      tyrosine kinases play crucial roles in mammalian cellular metabolism by
      regulating intracellular signaling pathways that control proliferation,
      differentiation, cytokine gene induction and cytokine responsiveness, matrix
      metalloproteinase gene expression, mechanical transduction, as well as programmed
      cell death (apoptosis). Many of these pathways are also important components of
      cartilage homeostasis because alterations in intracellular signaling pathways
      appear to play a prominent role in chondrocyte dysfunction that is part of
      osteoarthritis pathogenesis and disease progression. Several mitogen-activated
      protein kinases and receptor-tyrosine kinases have been characterized as
      participating in chondrocyte signaling pathways. They are c-Jun-amino-terminal
      protein kinase, p38 kinase, extracellular signal-regulated protein kinase, and
      Ror2. Janus kinases and signal transducers and activators of transcription
      factors (Janus kinase/signal transducers and activators of transcription pathway)
      are also implicated in modulating the chondrogenic phenotype. Mitogen-activated
      protein kinase activation is required for their role as phosphorylating enzymes.
      Activation results from mitogen-activated protein kinase phosphorylation carried
      out by at least seven upstream kinases known as mitogen-activated protein kinase
      kinases. Additional upstream kinases (for example, MKKKKs and MKKKs) often
      require low molecular weight GTP-binding proteins to mediate the mitogen
      activated protein-kinase kinases cascade. Identifying the functions of mitogen
      activated protein kinases in normal and aging cartilage and the extent to which
      mitogen-activated protein kinases may be altered in osteoarthritis cartilage and
      synovium will be critical for developing novel therapies for osteoarthritis
      management.

PMID- 15480060
TI  - Risk factors for osteoarthritis: understanding joint vulnerability.
AB  - Joint damage occurs when structures protecting the joint fail. Because
      osteoarthritis consists of end-stage joint damage, I propose that risk factors
      for disease can be best understood as either impairments of joint protectors,
      increasing joint vulnerability, or as factors that excessively load the joint,
      leading to injury. I review current knowledge using this paradigm, separating
      factors into those increasing joint vulnerability (malalignment, muscle weakness,
      genetic and ethnic predispositions, aging) and those that cause excessive loading
      (obesity; certain physical activities). Osteoarthritis and cartilage loss can
      occur without pain. This review focuses separately on factors associated with
      pain in those with osteoarthritis. To identify sources of pain in osteoarthritis,
      recent studies have compared magnetic resonance imaging findings of people with
      osteoarthritis with and without pain, focusing on structures known to have
      nociceptive innervations. Those with pain are more likely to have effusions, bone
      marrow lesions, synovial hypertrophy, and tendinitis and bursitis around the
      joint. This review creates a new paradigm for understanding risk factors for
      osteoarthritis, using joint vulnerability and loading as a framework and focuses
      separately on the emerging investigative area of sources of pain.

PMID- 15480059
TI  - Hyaluronan and CD44: modulators of chondrocyte metabolism.
AB  - Stability of cell-matrix interactions promotes tissue homeostasis, and matrix
      receptors provide for the assembly and retention of matrix as well as the linkage
      to the signal transduction pathways activated in response to changes within the
      extracellular matrix. Therefore, changes in cell-matrix interactions may
      influence cell responses to cytokines and cell survival and may facilitate tissue
      remodeling. Matrix components sequester or present soluble morphogens to their
      signaling receptors. Another layer of complexity would be the establishment of
      new or uncoupling of cell-matrix interactions, leading to altered cellular
      response to morphogens. The hyaluronan receptor CD44 serves as the critical link
      for the retention of hyaluronan-proteoglycan aggregates to the chondrocyte cell
      surface. As we continue to define functional chondrocyte CD44, future studies
      will need to include analysis of the variant CD44 isoform expression,
      phosphorylation, cytoskeletal interactions, occupancy, and turnover. Disruption
      of chondrocyte CD44:hyaluronan interaction will induce a cascade of events
      resulting in the activation of both catabolic as well as anabolic gene products.
      Fragments of hyaluronan produced in free radical processes have the potential to
      augment the production of nitric oxide in a CD44-dependent mechanism. Data also
      support an emerging paradigm that CD44-mediated signaling affects both
      chondrocyte survival pathways as well as apoptotic pathways.

PMID- 15480061
TI  - Up-regulation of chondrocyte matrix genes and products by electric fields.
AB  - This study tested the hypothesis that selective and specific capacitively coupled
      electrical signals could stimulate gene expression and matrix production in
      bovine articular chondrocytes. Starting with a capacitively coupled electric
      signal that previously was shown to be effective in stimulating proliferation in
      bovine articular cartilage chondrocytes, dose responses were done sequentially
      for duration, response time, amplitude, duty cycle, and frequency. Results showed
      that a 0.5-hour, 20 mV/cm, signal at 60 kHz up-regulated aggrecan gene expression
      approximately eightfold (p < 0.0003) using a 50% duty cycle, whereas Type II
      collagen gene expression was up-regulated approximately fivefold (p < 0.02) using
      an 8.3% duty cycle. Using a compound signal (a 0.5-hour continuous period plus
      multiple 1-hour periods of 50% duty cycle for 7 days) both proteoglycan and
      collagen accumulation in vitro were increased approximately fivefold (p < 0.0003)
      and twofold (p < 0.0008), respectively. Also, the most effective capacitively
      coupled electric signal was different for each of the two molecules studied
      (aggrecan, 50% duty cycle and 4-hour response time; Type II collagen, 8.3% duty
      cycle and 6-hour response time). We conclude that selective up-regulation of gene
      expression and matrix accumulation of cartilage structural macromolecules (such
      as aggrecan and Type II collagen) with specific capacitively coupled fields
      occurs in vitro. This may be useful in vivo as a noninvasive modality to promote
      cartilage healing or ameliorate the effects of osteoarthritis, or both.

PMID- 15480063
TI  - Toward imaging biomarkers for osteoarthritis.
AB  - Many new therapeutic strategies have been and are being developed to correct,
      prevent, or slow the progression of osteoarthritis. Our ability to evaluate the
      efficacy of these techniques, or to determine the situations for which they might
      provide the most benefit, critically depends on diagnostic measures that can
      serve as proxies for the present or predicted state of the cartilage. Many of the
      magnetic resonance imaging techniques that have been emerging over the past
      decades appear promising in that they have shown technical validity in measuring
      the morphologic and molecular state of cartilage. With continued development and
      added insight from pilot clinical studies, these or related methods may soon be
      in customary use. These techniques are part of a paradigm shift where therapeutic
      strategies are developed hand-in-hand with diagnostic approaches-a shift that
      offers the promise of speeding development of effective therapies, and focusing
      their use in areas where they can be most successful.

PMID- 15480065
TI  - Osteoarthritis: current treatment and future prospects for surgical, medical, and
      biologic intervention.
AB  - The treatment of osteoarthritis includes a wide spectrum of approaches. This
      article reviews current practices in medical, pharmaceutical and surgical
      treatment with a perspective toward the immediate, distant and far distant
      future. At present, with the exception of surgery, all other treatments are
      palliative. That is to say that many of these treatments relieve pain and
      increase function. However, on the basis of medical evidence, these treatments do
      not change the course of the disease. Surgical interventions, including joint
      replacement and osteotomy, reverse the progress of osteoarthritis and provide
      long-term improved function and pain relief for specific joints. The goal of
      treating osteoarthritis is to arrest and reverse its progress regionally or
      globally through biologic methodology. Meaningful progress for biologic
      intervention accumulates annually. Pluripotent mesenchymal cells can be coaxed
      into chondrocytes or stem cells. Cytokines, growth factors, chemokines, protease
      inhibitors, kinases, apoptosis, mechanics, and genetics are increasingly
      recognized to play key roles in the control of the articular cartilage behavior.
      Knowledge of their roles and relationships advance toward solutions related to
      osteoarthritis. In the future, biologic control may be harnessed to regrow joints
      or limbs, as currently occurs naturally in newts and salamanders. Fortunately,
      until then we have ever improving joint replacement.

PMID- 15480066
TI  - Functional tissue engineering parameters toward designing repair and replacement
      strategies.
AB  - Abnormal joint kinematics and loads induced after soft tissue injuries are
      assumed to contribute to long-term degenerative joint disease and osteoarthritis.
      Controlling abnormal kinematics after repair and reconstruction of these injured
      structures would seem to be important for limiting wear of the articular
      cartilage surfaces. In this paper, we propose to expand the paradigm of
      functional tissue engineering to more fully characterize normal joint function
      and to establish design parameters for soft tissue repair and reconstruction to
      ultimately protect joint surfaces after surgery. Structure-function relationships
      are examined for tissues of increasing complexity, from tendons to menisci.
      Emphasis is placed on understanding normal in vivo function of tissues by
      conducting biomechanical experiments in vitro that better mimic in vivo
      conditions. This process yields nine classes of functional tissue engineering
      parameters: differential fiber length, in vivo force and displacement, variations
      in relative attachment site locations, loading from adjacent structures, fiber
      interactions, types of insertion, regional variations in material properties,
      nonparallel fiber orientations, and complex loading within the structure. These
      functional tissue engineering parameters are useful not only for understanding
      the function of normal tissues but for more effectively designing their repair
      and replacement. This paper concludes with a discussion of research directions
      that investigators might take to establish tissue-specific functional tissue
      engineering parameters for improving joint function and reducing articular
      surface degradation and osteoarthritis.

PMID- 15480068
TI  - Familial inheritance of osteoarthritis: documented family subsets.
AB  - Identifying susceptibility genes for a common complex disease is complicated by
      heterogeneity at several levels including allelic, locus, clinical, and
      population. The latter two can be alleviated by focusing on particular subsets of
      families that have well-defined disease. For osteoarthritis it was commonly
      thought that a generalized disease approach was the wisest ascertainment because
      this would target a systemic disease that had to have a major genetic component.
      However, this intuitive idea has not yet provided the breakthroughs many expected
      and it has become apparent that a joint-specific and gender-specific approach may
      be more fruitful. Large collections of osteoarthritis cohorts have been assembled
      either as part of prospective studies or more directly. Some of these collections
      have targeted specific joints, others have not. The latter are, however, amenable
      to stratification. Many collectors included the acquisition of DNA as a core
      study aim. A variety of osteoarthritis subsets are therefore available for
      genetic analysis. Open accessibility is another matter. Although many collections
      were funded partly or wholly by public or charitable organizations, they can be
      jealously guarded or have arcane access rights. Open access, with necessary
      safeguards, is something the osteoarthritis research community should strive for
      if progress toward susceptibility gene identification is to be swift.

PMID- 15480070
TI  - The role of cytokines in cartilage matrix degeneration in osteoarthritis.
AB  - Chondrocytes are the single cellular component of hyaline cartilage. Under
      physiologic conditions, they show steady-state equilibrium between anabolic and
      catabolic activities that maintains the structural and functional integrity of
      the cartilage extracellular matrix. Implicit in the loss of cartilage matrix that
      is associated with osteoarthritis is that there is a disturbance in the
      regulation of synthetic (anabolic) and resorptive (catabolic) activities of the
      resident chondrocytes that results in a net loss of cartilage matrix components
      and deterioration in the structural and functional properties of the cartilage.
      Multiple mechanisms likely are involved in the disturbance of chondrocyte
      remodeling activities in OA. They include the development of acquired or age
      related alterations in chondrocyte function, the effects of excessive mechanical
      loading, and the presence of dysregulated cytokine activities. Cytokines are
      soluble or cell-surface molecules that play an essential role in mediating cell
      cell interactions. It is possible to classify the cytokines that regulate
      cartilage remodeling as catabolic, acting on target cells to increase products
      that enhance matrix degradation; as anticatabolic, tending to inhibit or
      antagonize the activity of the catabolic cytokines; and as anabolic, acting on
      chondrocytes to increase synthetic activity. This review will focus on the role
      of proinflammatory cytokines and their roles in mediating the increased matrix
      degradation that characterizes the osteoarthritic cartilage lesion.

PMID- 15480071
TI  - Commentaries on the history and cure of diseases. Digitorum Nodi by William
      Heberden MD.

PMID- 15480072
TI  - The regulation of chondrocyte function by proinflammatory mediators:
      prostaglandins and nitric oxide.
AB  - Within the mature articular cartilage matrix, which has no blood or nerve supply,
      chondrocytes show little metabolic activity with low turnover of matrix
      components. Under conditions of stress because of biomechanical factors, however,
      chondrocytes are capable of producing mediators that are associated with
      inflammation, including cytokines such as interleukin-1 and tumor necrosis factor
      alpha, which in turn stimulate the production of prostaglandins and nitric oxide.
      Chondrocytes also express receptors for these mediators, which accumulate at high
      local concentrations and can act in an autocrine-paracrine fashion to feedback
      regulate chondrocyte responses. Prostaglandin E2 can exert catabolic or anabolic
      effects depending on the microenvironment. Nitric oxide can promote cellular
      injury and increase chondrocyte susceptibility to cytokine-induced apoptosis.
      Because cross-talk between these mediators produces complex modulation of
      catabolic and anabolic pathways, further studies in vitro and in vivo are
      required to elucidate their precise roles in osteoarthritis.

PMID- 15480073
TI  - Growth factor inhibition: potential role in the etiopathogenesis of
      osteoarthritis.
AB  - Growth factors are small proteins that regulate cellular function. Some growth
      factors, including insulin like growth factor-1 and transforming growth factor
      beta play an anabolic role in articular cartilage. The loss of articular
      cartilage that occurs in osteoarthritis may reflect, in part, an insufficiency of
      such factors. Recent evidence suggests that inhibition of these growth factors
      may contribute to the disease process in osteoarthritis. Inhibitors identified to
      date include binding proteins, cytokines, mechanical factors, and nutritional
      status. The mechanisms underlying the actions and interactions of these
      regulatory factors are beginning to be elucidated and may have implications for
      the development of new approaches to the treatment of osteoarthritis.

PMID- 15480075
TI  - Chemokines in cartilage degradation.
AB  - Besides the well-known activities of the prototypical inflammatory cytokines (IL
      1beta, TNFalpha), a role for chemokines and their receptors in cartilage
      degradation in osteoarthritis has recently been reported. Human chondrocytes can
      produce CC and CXC chemokines and express chemokine receptors for both chemokine
      subfamilies. Engagement of these receptors can induce the release of matrix
      degrading enzymes such as matrix metalloproteinases 1, 3, and 13, and N-acetyl
      beta-D-glucosaminidase. Furthermore GROalpha, a CXC chemokine acting on CXCR2,
      can activate an apoptotic pathway in chondrocytes that leads to chondrocyte cell
      death. These findings suggest that chemokines can act as an autocrine or
      paracrine loop on chondrocytes and can contribute to many pathophysiological
      patterns present in osteoarthritis. Chemokines and their downstream signaling
      pathways can be considered novel therapeutic targets in osteoarthritis.

PMID- 15480076
TI  - The impact of osteoarthritis: implications for research.
AB  - Osteoarthritis, the clinical syndrome of joint pain and dysfunction caused by
      joint degeneration, affects more people than any other joint disease. There are
      no consistently effective methods for preventing osteoarthritis or slowing its
      progression, and symptomatic treatments provide limited benefit for many
      patients. Osteoarthritis disables about 10% of people who are older than 60
      years, compromises the quality of life of more than 20 million Americans, and
      costs the United States economy more than $60 billion per year. The incidence of
      osteoarthritis rises precipitously with age; as a result, the prevalence and
      burden of this disorder is increasing rapidly. Study of the patterns
      osteoarthritis incidence and prevalence shows that it occurs frequently in the
      hand, foot, knee, spine and hip, but rarely in the ankle, wrist, elbow, and
      shoulder, and the most important universal risk factors are age, excessive joint
      loading, and joint injury. Analysis of the impact of osteoarthritis raises
      questions that include: Why does the incidence increase progressively with age?
      Why are some joints rarely affected? How do mechanical forces cause joint
      degeneration? What biologic and mechanical factors slow or accelerate the rate of
      joint degeneration? Answering these questions could lead to effective methods of
      preventing osteoarthritis and slowing its progression.

PMID- 15480077
TI  - Osteochondral defect repair by demineralized cortical bone matrix.
AB  - It has been reported that demineralized bone matrix (cortical or trabecular bone)
      contains intrinsic cytokines. In the present study, we tested allogeneic
      demineralized bone matrix for its capacity to resurface osteochondral defects in
      a rabbit model with the assumption that the intrinsic cytokines in demineralized
      bone matrix will facilitate the recruitment of progenitor cells from bone marrow
      into the defect. It was further assumed that these intrinsic bioactive factors
      would modulate these cells to differentiate into osteochondrogenic lineage and,
      thus, functionally repair the osteochondral defect. The biocompatibility of
      demineralized bone matrix was first tested by loading rabbit bone-marrow-derived
      mesenchymal stem cells into porous demineralized trabecular bone matrix that was
      then cultured for 3 days. The cell growth in demineralized trabecular bone matrix
      was examined by scanning electron microscopy. Loaded rabbit bone-marrow-derived
      mesenchymal stem cells attached to the trabeculae of demineralized trabecular
      bone matrix; some cells appeared to be round and others were spread and contacted
      other cells. Allogeneic rabbit demineralized cortical bone matrix or
      demineralized trabecular bone matrix was implanted into a full-thickness
      osteochondral defect in the load-bearing area of the medial femoral condyle of
      young adult rabbits. At 6 and 12 weeks after surgery, gross and histological
      examination showed that the defects were repaired up to 95% of their depth. The
      repair tissue using demineralized cortical bone matrix was composed of
      subchondral bone and a top layer of cartilage that was smooth and integrated with
      the adjacent cartilage in most of the specimens. Most of the repair tissue in the
      defect filled with demineralized trabecular bone matrix had a fibrillated surface
      without integration with the adjacent cartilage. These results indicate that
      demineralized cortical bone matrix may be potentially useful to repair
      osteochondral defects by managing the host's intrinsic reparative cells.

PMID- 15480079
TI  - The mechanobiology of articular cartilage development and degeneration.
AB  - The development, maintenance, and destruction of cartilage are regulated by
      mechanical factors throughout life. Mechanical cues in the cartilage fetal
      endoskeleton influence the expression of genes that guide the processes of
      growth, vascular invasion, and ossification. Intermittent fluid pressure
      maintains the cartilage phenotype whereas mild tension (or shear) promotes growth
      and ossification. The articular cartilage thickness is determined by the position
      at which the subchondral growth front stabilizes. In mature joints, cartilage is
      thickest and healthiest where the contact pressure and cartilage fluid pressure
      are greatest. The depth-dependent histomorphology reflects the local fluid
      pressure, tensile strain, and fluid exudation. Osteoarthritis represents the
      final demise and loss of cartilage in the skeletal elements. The initiation and
      progression of osteoarthritis can follow many pathways and can be promoted by
      mechanical factors including: (1) reduced loading, which activates the
      subchondral growth front by reducing fluid pressure; (2) blunt impact, causing
      microdamage and activation of the subchondral growth front by local shear stress;
      (3) mechanical abnormalities that increase wear at the articulating surface; and
      (4) other mechanically related factors. Research should be directed at
      integrating our mechanical understanding of osteoarthritis pathogenesis and
      progression within the framework of cellular and molecular events throughout
      ontogeny.

PMID- 15480080
TI  - Pathomechanic determinants of posttraumatic arthritis.
AB  - The etiology of posttraumatic arthritis is poorly understood. One possible
      mechanism involves a mechanical insult to the cartilage matrix that affects
      chondrocyte function. To better understand the etiology of posttraumatic
      arthritis, pathomechanic changes in articular contact mechanics resulting from
      injury during physiologic motion and loading need to be determined. Previous
      studies of injury-associated changes in articular contact mechanics, using static
      testing methods, have measured relatively modest increases in contact stresses.
      Static testing cannot measure transient loads associated with motion or loading
      rates. This testing method poorly simulates normal viscoelastic cartilage
      properties, and accounts for contact stress changes in a single or limited number
      of joint positions. In this study, time-variant contact stresses in two ankles
      with an anterolateral stepoff were measured during quasiphysiologic motion and
      loading. Contact stresses were integrated over the entire range of motion to
      estimate pathomechanic loads that accumulate over the entire motion cycle.
      Numerical techniques were applied to time-variant contact stress data to
      calculate contact stress directional gradients and contact stress rates of
      change. Contact stress directional gradients and rates of change were integrated
      over the complete motion cycle to estimate whole-cycle accumulation of these
      potential pathomechanic parameters.

PMID- 15480081
TI  - Pressure and shear differentially alter human articular chondrocyte metabolism: a
      review.
AB  - Homeostasis of articular cartilage depends in part on mechanical loads generated
      during daily activity whereas inappropriate joint loads result in focal
      degeneration of cartilage, as occurs in osteoarthritis. We will review results of
      a series of questions regarding the effects of two types of mechanical loads
      intermittent hydrostatic pressure and shear stress-on adult human articular
      chondrocytes in high-density monolayer culture. Intermittent hydrostatic pressure
      increased aggrecan and Type II collagen gene expression in normal chondrocytes
      and induced changes in the cell-associated proteins of normal and osteoarthritic
      chondrocytes. Hydrostatic pressure also counteracted inhibitory effects of
      bacterial lipopolysaccharide on matrix protein expression by cultured
      chondrocytes. Application of shear stress to osteoarthritic chondrocytes
      increased the release of the proinflammatory mediator, nitric oxide, decreased
      aggrecan and Type II collagen expression, and induced molecular changes
      associated with apoptosis whereas hydrostatic pressure increased matrix
      macromolecule expression. The findings show that the types of load comprising the
      mechanical loading environment of articular cartilage considerably alter
      chondrocyte metabolism and suggest that mechanical stimulation may be used for in
      vitro or in vivo approaches for cartilage engineering.

PMID- 15480082
TI  - Chondrocyte senescence, joint loading and osteoarthritis.
AB  - cellular level is not completely understood, but both aging and loading-induced
      stresses have been shown to undermine cell functions related to the maintenance
      and restoration of the cartilage matrix. Based on precedents set by studies of
      other age-related degenerative diseases, we have focused our laboratory work on
      senescence as the cause of age-dependent decline in chondrocytes and on the
      impact of excessive mechanical stresses in promoting senescence. We hypothesized
      that senescent chondrocytes accumulate with age in articular cartilage and we
      propose that excessive mechanical stress plays a role in this process by
      promoting oxidative damage in chondrocytes that ultimately causes them to
      senesce. To test this hypothesis, we measured cell senescence markers (beta
      galactosidase expression, mitotic activity, and telomere length) in human
      articular cartilage chondrocytes, and determined the effects of chronic exposure
      to oxidative stress on chondrocyte growth and senescence. In addition, we
      measured the effects of abnormally high levels of mechanical shear stress on the
      release of oxidants in cartilage explants. We found that senescent chondrocytes
      accumulated with age in articular cartilage. In vitro studies showed that chronic
      oxidative stress caused by repeated exposure to peroxide, or by growth under
      superphysiologic oxygen tension caused chondrocyte populations to senesce
      prematurely, before extensive telomere erosion occurred. Mechanical shear stress
      applied to cartilage explants considerably increased the production of oxidants.
      These observations support the hypothesis that senescence accounts for age
      related decline in chondrocyte function and indicate that mechanically induced
      oxidative damage plays a role in this process. This suggests that new efforts to
      prevent the development and progression of osteoarthritis should include
      strategies that slow the progression of chondrocyte senescence or replace
      senescent cells.

PMID- 15480083
TI  - Lifestyle interventions or drugs for patients with essential hypertension: a
      systematic review.
AB  - OBJECTIVE: To compare the effectiveness of lifestyle and drug interventions for
      treating patients with essential hypertension. METHODS: Systematic review of
      randomized controlled trials (RCTs), with 8 or more weeks follow-up, enrolling
      patients with blood pressure of at least 140/85 mmHg, which directly compared
      lifestyle and drug interventions. Planned outcome measures were cardiovascular
      morbidity and mortality and blood pressure. RESULTS: We found five RCTs meeting
      our inclusion criteria and additionally included one quasi-randomized trial.
      These trials enrolled between 27 and 64 participants, mean age 55 years, with
      follow-up of less than 1 year; none reported cardiovascular outcomes. The
      lifestyle and drug interventions and patient populations were heterogeneous.
      Overall, the trials were of poor quality and had inconsistent results. Although
      dietary interventions did not always lower blood pressure as much as
      antihypertensive drugs, secondary analysis suggested that they might be better at
      lowering cholesterol levels. CONCLUSIONS: In the short term, lifestyle treatment
      may be effective at reducing blood pressure for some individuals. A healthier
      diet, by lowering blood pressure and cardiovascular risk, may reduce, delay or
      remove the need for long-term drug therapy in some patients. However, further
      comparisons of lifestyle and drug interventions for hypertension are required,
      with larger clinical trials of longer duration and better quality. Future trials
      should aim to identify the characteristics of patients most likely to benefit
      from lifestyle changes.

PMID- 15480084
TI  - Insufficient evidence to conclude whether or not Transcendental Meditation
      decreases blood pressure: results of a systematic review of randomized clinical
      trials.
AB  - OBJECTIVE: To carry out an independent, systematic review of randomized clinical
      trials of Transcendental Meditation (TM) for cumulative effects on blood
      pressure. METHOD: Searches were made of electronic databases and the collected
      papers and official web sites of the TM organization. We included only randomized
      clinical trials, without confounding co-interventions, which measured the
      cumulative effects of TM on blood pressure. RESULTS: Six trials met the inclusion
      criteria but one, reported only in abstract form, could not be evaluated.
      Procedures for establishing baseline blood pressure were adequate in only one
      trial. Only one of the trials included a follow-on assessment and only one of the
      evaluable trials tested the effect of TM in hypertensive individuals. Three of
      the five evaluable trials reported statistically significant differences between
      intervention groups favouring TM and two found no significant differences between
      intervention groups. None of the five studies was conducted by independent
      authors without any affiliation to the TM organization. CONCLUSION: All the
      randomized clinical trials of TM for the control of blood pressure published to
      date have important methodological weaknesses and are potentially biased by the
      affiliation of authors to the TM organization. There is at present insufficient
      good-quality evidence to conclude whether or not TM has a cumulative positive
      effect on blood pressure.

PMID- 15480085
TI  - Are guidelines right to promote lifestyle interventions against hypertension?

PMID- 15480086
TI  - Stress reduction and blood pressure control in hypertension: a role for
      transcendental meditation?

PMID- 15480087
TI  - Assessing circadian blood pressure and heart rate changes: advantages and
      limitations of different methods of mathematical modelling.

PMID- 15480088
TI  - Reduced nephron number, renal development and 'programming' of adult
      hypertension.

PMID- 15480089
TI  - Fat distribution, body mass index and blood pressure in 22,090 men and women in
      the Norfolk cohort of the European Prospective Investigation into Cancer and
      Nutrition (EPIC-Norfolk) study.
AB  - OBJECTIVE: To determine the relation between fat distribution and blood pressure,
      independent of body mass index. DESIGN: Cross-sectional, population-based study.
      PARTICIPANTS AND METHODS: Participants, 9936 men and 12,154 women aged 45-79
      years, were recruited from general practices in Norfolk, United Kingdom for the
      European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk)
      study. Participants filled in a health and lifestyle questionnaire and their
      blood pressure and anthropometry were measured at a clinic. We mainly used waist
      hip ratio (WHR) to assess body fat distribution. RESULTS: Systolic blood pressure
      (SBP) and diastolic blood pressure (DBP) increased linearly across the whole
      range of waist-hip ratio in both men and women. The relation was independent of
      age, body mass index (BMI) and other covariates. Separately, waist and hip
      circumferences were positively related to SBP and DBP. When adjusted for BMI,
      waist circumference was positively related to SBP (in women) and DBP (in both men
      and women), whereas hip circumference was inversely related to SBP (but not DBP)
      in both men and women. Stratifying by tertiles of waist and hip circumference,
      age- and BMI-adjusted SBP and DBP were highest among those with high waist and
      small hip circumference measures. CONCLUSION: Waist-hip ratio was independently
      related to blood pressure. Waist-hip ratio could reflect the separate and
      opposite relations of waist and hip circumferences on blood pressure.
      Characterizing patterns of fat distribution may have implications in the
      assessment and control of obesity-related blood pressure elevation.

PMID- 15480090
TI  - Non-symmetrical double-logistic analysis of 24-h blood pressure recordings in
      normotensive and hypertensive rats.
AB  - OBJECTIVE: To determine the suitability of a new logistic curve fitting procedure
      to measure the diurnal rates of transition from the active to the asleep periods
      separately. METHOD: We applied this method to 24-h telemetry recordings of
      systolic, mean, diastolic arterial pressure (SAP, MAP, DAP, respectively), heart
      rate (HR) and locomotor activity of normotensive Sprague-Dawley rats (SDR) and
      spontaneously hypertensive rats (SHR). RESULTS: There was a similar pattern of
      higher awake and lower sleep values (16 +/- 1 mmHg SAP, 77 +/- 2 bpm HR and 40 +/
      2 units activity) in SHR. In SDR, awake-asleep differences were less for SAP (9
      +/- 1 mmHg) but similar for HR (83 +/- 2 bpm). In SHR, while the blood pressure
      patterns were symmetrical, the rate of rise in activity and HR during arousal was
      more rapid than the rate of decline during the dark to light transition. By
      contrast in SDR, the arousal rate of increase in blood pressure and HR was much
      less than the rate of decline. Thus SHR have an exaggerated arousal surge in DAP
      compared with SDR. Double logistic provides a better fit than Cosinor or square
      wave and better estimates of day-night differences than partial Fourier.
      CONCLUSIONS: Analysis of 24-h recordings by a new logistic curve method reveals
      distinct asymmetric circadian patterns of cardiovascular and activity changes in
      rats. The greater surge in arousal blood pressure in SHR is not associated with
      differences in HR or activity changes and may be inherent to the underlying
      mechanisms contributing to the hypertension in SHR.

PMID- 15480091
TI  - Relation of nocturnal blood pressure dipping to cellular adhesion, inflammation
      and hemostasis.
AB  - BACKGROUND: Subjects who fail to dip their nocturnal blood pressure (BP) are at
      substantially increased risk for cardiovascular diseases. The pathogenetic
      mechanisms of this relationship have not been elucidated. We investigated whether
      non-dipping would relate to procoagulant and proinflammatory activity. DESIGN:
      Study participants were 76 unmedicated normotensive and hypertensive subjects (44
      male, 32 female; 41 white, 35 black; mean age, 36 +/- 8 years) who underwent 24-h
      outpatient ambulatory BP monitoring. Based on whether their average nocturnal
      systolic BP relative to their average daytime systolic BP declined by less than
      10%, 34 subjects were categorized as non-dippers. D-dimer, plasminogen activator
      inhibitor-1, von Willebrand factor, soluble intercellular adhesion molecule-1,
      and interleukin-6 were measured in plasma. RESULTS: Multivariate analyses showed
      that D-dimer (median/interquartile range, 242/162-419 ng/ml versus 175/132-254
      ng/ml; P=0.041), plasminogen activator inhibitor-1 (36/19-61 ng/ml versus 17/6-44
      ng/ml; P=0.010), von Willebrand factor (122/91-179% versus 92/66-110%; P=0.001),
      and soluble intercellular adhesion molecule-1(227/187-291 ng/ml versus 206/185
      247 ng/ml; P=0.044) were all higher in non-dippers than in dippers. Adjustment
      for gender, ethnicity, age, body mass index, smoking status, hypertension status,
      and social class revealed independent effects of non-dipping. Non-dippers
      continued to have higher D-dimer (P=0.030) and von Willebrand factor (P=0.034)
      than dippers. A similar trend not reaching statistical significance emerged for
      soluble intercellular adhesion molecule-1 (P=0.055). In contrast, dipping status
      had no effect on interleukin-6. CONCLUSION: Nocturnal BP non-dipping is
      associated with elevated levels of molecules related to endothelial dysfunction
      and atherosclerosis. The finding provides one possible mechanism linking non
      dipping with cardiovascular disease.

PMID- 15480092
TI  - Retinal microvascular changes and target organ damage in untreated essential
      hypertensives.
AB  - BACKGROUND AND PURPOSE: The clinical and prognostic significance of initial
      retinal alterations in hypertensive patients remains controversial. Therefore, we
      assessed the relationship of microvascular abnormalities with prognostically
      validated markers of target organ damage (TOD), such as left ventricular mass
      (LVM), carotid intima-media thickness (IMT) and microalbuminuria, in early stages
      of untreated essential hypertension. METHODS: A total of 437 consecutive, never
      treated patients with grade 1 or 2 essential hypertension, referred to our
      outpatient clinic, underwent the following procedures: (1) clinical and routine
      laboratory examinations, (2) 24-h ambulatory blood pressure monitoring, (3) 24-h
      urine collection for microalbuminuria, (4) echocardiography, (5) carotid
      ultrasonography, (6) non-mydriatic retinography. Patients were divided into group
      I, with either a normal retinal pattern (n=65, 14.9%) or arteriolar narrowing
      (n=185, 42.4%) and group II with arteriovenous crossings (n=187, 42.7%). RESULTS:
      The two groups were similar for gender, body mass index, smoking habit, heart
      rate, clinic and ambulatory blood pressure (BP) values, while mean age was
      slightly but significantly higher in group II than in group I (47.6 +/- 10.7
      versus 44.5 +/- 12.5 years, P=0.008). No differences occurred between the two
      groups in LVM index (101.8 +/- 18.5 versus 99.9 +/- 20.4 g/m), carotid IMT (0.67
      +/- 0.12 versus 0.66 +/- 0.20 mm), urinary albumin excretion rate (14.4 +/- 27.7
      versus 13.3 +/- 27.7 mg/24 h) as well as in the prevalence of LV hypertrophy
      (14.3 versus 14.0%), IM thickening and/or plaques (26.5 versus 27.2%) (both
      defined according to 2003 ESH-ESC guidelines) and microalbuminuria (10.1 versus
      8.7%). Furthermore, the three different retinal artery patterns were similarly
      distributed among tertiles of LV mass index, IMT and urinary albumin excretion
      rate. CONCLUSIONS: These results show that: (1) a very large fraction (more than
      80%) of untreated, recently diagnosed hypertensive patients have initial retinal
      microvascular abnormalities detectable by non-mydriatic retinography, (2) the
      presence of arteriovenous crossings is not associated with more prominent cardiac
      and extracardiac TOD, (3) fundoscopic examination has a limited clinical value to
      detect widespread organ involvement in early phases of grade 1 and 2
      hypertension.

PMID- 15480093
TI  - Exaggerated response to cold stress in a congenic strain for the quantitative
      trait locus for blood pressure.
AB  - OBJECTIVE: Stroke-prone spontaneously hypertensive rats (SHRSP) are known to have
      sympathetic hyperactivity to various stimuli. In the search for 'intermediate
      phenotypes' inferring the function of hypertension genes, the present study
      assessed responsiveness to cold stress in a congenic strain derived from
      SHRSP/Izm and Wistar-Kyoto/Izm (WKY/Izm). DESIGN: A congenic strain, WKYpch1.0,
      was established by 10 generations of backcrossing to transfer the chromosomal
      fragment between D1Wox29 and D1Arb21 of SHRSP to WKY. This fragment covered the
      100:1 confidence interval of the quantitative trait locus (QTL) for blood
      pressure identified in a previous study. Response to cold stress was studied by
      exposing rats to 4 degrees C for 4 h. Blood pressure was monitored with
      telemetry. Urine was collected during the exposure, and urinary concentrations of
      catecholamines were measured by high-performance liquid chromatography. RESULTS:
      Under the cold stress, urinary excretion of norepinephrine (NE) and
      vanillylmandelic acid (VMA), as well as the plasma level of NE, was significantly
      greater in WKYpch1.0 than in WKY. The increase in blood pressure during the cold
      stress was also greater in WKYpch1.0 than in WKY. Further, neonatal chemical
      sympathectomy using guanethidine abolished the exaggerated response in blood
      pressure and in urinary excretion of NE and VMA in WKYpch1.0. CONCLUSION: These
      results suggested that the QTL region on rat chromosome 1 harbored genes
      responsible for the exaggerated response of the sympathetic nervous system to the
      cold stress. The relationship of this with the pathogenesis of hypertension
      should be elucidated in future studies.

PMID- 15480094
TI  - Haplotypes of the beta2-adrenergic receptor gene are associated with essential
      hypertension in a Singaporean Chinese population.
AB  - OBJECTIVE: To investigate the relation between the gene encoding the beta2
      adrenergic receptor (B2AR) and essential hypertension in a Singaporean Chinese
      cohort. METHODS: Three single nucleotide polymorphisms (SNPs) were genotyped in
      190 cases and 323 controls, and eight haplotypes were determined and tested for
      association using the likelihood test statistic. RESULTS: We observed a
      significant difference in haplotype frequency distributions between the cases and
      the controls (P <0.00001). A logistic regression model fitted to the data
      supported this finding. CONCLUSION: The results suggest that variants at the B2AR
      locus may play a role in the pathophysiology of hypertension in this population.

PMID- 15480095
TI  - The Glu27 allele of the beta2 adrenergic receptor increases the risk of cardiac
      hypertrophy in hypertension.
AB  - OBJECTIVE: Cardiac and vascular remodeling occur in response to hypertension.
      Genetic background appears to modify the development of target organ damage
      (TOD). We evaluated the impact on hypertension-associated TOD of a highly
      polymorphic gene with elevated significance for the regulation of the
      cardiovascular system, the beta2AR gene. METHODS: We recruited 775 hypertensives
      (mean +/- SE: age 53.5 +/- 0.5, from 20 to 84 years; female 32.7%; systolic
      (SBP)/diastolic (DBP) blood pressure: 159 +/- 1.2/101 +/- 0.6 mmHg) referred to
      the departmental outpatient clinic and screened them for the Arg16Gly, Gln27Glu,
      and Ile164Thr variants of beta2AR gene. We performed association analyses on
      clinical, anamnesis, anthropometrical and biochemical parameters as well as
      cardiac and vascular ultrasound. RESULTS: We found that the three polymorphisms
      did not affect blood pressure levels. Cardiac TOD appeared to be related to the
      Glu27 variant. In fact, the Glu27 allele associates with a 1.4-fold higher risk
      of developing cardiac hypertrophy, and directly correlated with larger systolic
      and diastolic left ventricle internal diameters. Vascular TOD was not affected by
      the three polymorphisms. Ancillary to our finding we observed that the Glu27
      variant is associated with a higher incidence of dyslipidemia. CONCLUSIONS: Our
      data indicate that beta2AR gene polymorphisms participate in the determination of
      cardiac TOD associated with hypertension.

PMID- 15480096
TI  - G2736A polymorphism of thiazide-sensitive Na-Cl cotransporter gene predisposes to
      hypertension in young women.
AB  - OBJECTIVE: The thiazide-sensitive Na-Cl cotransporter (TSC) is located in the
      distal renal tubules. Several mutations of the TSC gene cause Gitelman's
      syndrome, which is an autosomal recessive disease characterized by low blood
      pressure and hypokalemia. Recently, an association between TSC gene polymorphisms
      (Arg904Gln, G2736A; Thr465Thr, C1420T; Gly264Ala, G816C) and essential
      hypertension has been reported in Sweden. We examined the genetic involvement of
      the TSC gene in essential hypertension in Japanese. DESIGN: Participants were
      recruited from outpatients of Osaka University Hospital. We investigated 386
      hypertensive and 371 normotensive subjects. METHODS: Genotypes of TSC
      polymorphisms (G2736A, C1420T, G816C) were determined by the TaqMan polymerase
      chain reaction (PCR) method, and statistical significance was examined using JMP
      5.0.1J (SAS Institute Inc., Cary, North Carolina, USA). The allele frequency of
      A2736 and T1420 was 6.0 and 3.0%, respectively, whereas we could not detect the
      G816C polymorphism in this study. Only the G2736A polymorphism was significantly
      associated with the prevalence of hypertension (P <0.04), and the estimated odds
      ratio was 1.8 (95% confidence interval, 1.1-3.0) in A2736 allele carriers. The
      odds ratio for hypertension in A2736 carriers was increased to 2.2 (1.1-4.9) in
      women (n=413), and further to 3.3 (1.4-8.0) in women with early onset of
      hypertension (< or = 50 years old). In addition, all subjects with the homozygous
      A2736 allele in this study (n=2) and the Swedish study (n=5) were hypertensive.
      CONCLUSION: G2736A polymorphism of the TSC gene is a genetic predisposing factor
      for essential hypertension in Japanese women.

PMID- 15480097
TI  - Gene polymorphisms of the renin-angiotensin-aldosterone system and the risk of
      ischemic stroke: a role of the A1166C/AT1 gene variant.
AB  - OBJECTIVE: The role of the renin-angiotensin-aldosterone system (RAAS) genes on
      predisposition to develop stroke, a multifactorial and polygenic cardiovascular
      trait, is still under investigation. In the present study we characterized the
      contributory role of RAAS genes in the susceptibility to develop ischemic stroke
      in humans. METHODS: Allele and genotype frequencies of RAAS genes were
      characterized in a population of 215 cases (including only atherothrombotic and
      lacunar forms) and 236 controls selected in Sardinia, a large Mediterranean
      island with a well-known segregated population. Statistical analysis was
      performed in the whole population and, based on a significant interaction between
      angiotensin II receptor (AT1) genotype and hypertension, was also repeated in the
      hypertensive subgroup. RESULTS: A significant association of the C1166/AT1 gene
      allelic variant with stroke was found when assuming a dominant model of
      transmission [unadjusted odds ratio (OR)=1.5, 95% confidence interval (CI) 1.1
      2.2, P=0.024]. The strength of the association became more evident in the
      subgroup of hypertensive individuals (135 cases and 110 controls). In fact, in
      this cohort the independent OR for the AT1 gene was 2.1, 95% CI 1.2-3.7, P=0.006
      in the dominant model and 2.0, 95% CI 1.3-3.2, P=0.002 in the additive model. No
      other RAAS gene was identified as a contributor to stroke. CONCLUSIONS: Our
      findings support a predisposing role of an AT1 gene variant in the development of
      ischemic stroke. In particular, the AT1 gene variant exerted a major impact on
      ischemic stroke occurrence in the presence of hypertension.

PMID- 15480098
TI  - A1166C polymorphism of angiotensin II type 1 receptor, blood pressure and
      arterial stiffness in hypertension.
AB  - OBJECTIVE: To study the association of the AC polymorphism of angiotensin II type
      1 receptor gene (AGTR1) with blood pressure and central arterial stiffness in a
      population of hypertensive patients referred to hospital for further work-up.
      METHODS: One hundred and eighty-five patients, referred to our department from
      April 1998 to February 2002, were included. Blood pressure was measured by
      conventional and 24-h ambulatory methods, and arterial stiffness by carotid
      femoral pulse wave velocity (PWV) determination. Genotyping for the AGTR1 AC
      polymorphism was performed by polymerase chain reaction. RESULTS: AGTR1 AC
      polymorphism was not associated with systolic or diastolic blood pressure,
      measured either by conventional (P=0.89 and P=0.67, respectively) or by 24-h
      ambulatory (P=0.57 and P=0.56, respectively) methods. Conversely, this
      polymorphism was significantly associated with PWV (P=0.006) and had a dose
      allele effect, PWV increasing with the number of A alleles (10.6 +/- 2.4 m/s in
      CC, 11.9 +/- 2.5 m/s in AC and 12.7 +/- 2.7 m/s in AA patients, P=0.002).
      Multiple regression analysis showed that AC polymorphism was still independently
      associated with PWV (P=0.01) and was the third most important determinant of PWV
      after age (P <0.0001) and 24-h mean blood pressure (P <0.0001). CONCLUSION: In
      our study population, central arterial stiffness assessed by PWV was
      significantly and independently associated with the AC polymorphism, increased
      PWV being associated with the presence of the A allele. Further investigations
      are required for identification of the underlying mechanisms.

PMID- 15480099
TI  - Tempol augments angiotensin II-induced AT2 receptor-mediated relaxation in
      diabetic rat thoracic aorta.
AB  - OBJECTIVE: To assess angiotensin II type 2 receptor-mediated responses in
      thoracic aorta of streptozotocin-induced diabetic rats. METHODS: The
      concentration-dependent relaxation response (in the presence of an AT1 receptor
      blocker) to angiotensin II (Ang II) was studied in phenylephrine (PE) or
      potassium chloride (KCl) precontracted rat thoracic aortic rings isolated from
      male Sprague-Dawley rats pretreated with streptozotocin (65 mg/kg i.p.) or
      vehicle 8 weeks prior to the study. RESULTS: Ang II-induced relaxation response
      (% relaxation), evident only in the presence of an AT1 receptor blocker, was
      significantly enhanced in aortic rings isolated from diabetic (55%) compared to
      control (25%) rats. Tempol (100 micromol/l) augmented the relaxation response in
      aortic rings isolated from diabetic (80%) but not control (28%) rats. N-nitro-l
      arginine methyl ester (L-NAME) (100-300 micromol/l) [a nitric oxide (NO) synthase
      inhibitor] partially inhibited the relaxation response in diabetic (25%) and
      control (15%) rats. However, l-NAME (100 micromol/l) and glipizide or butanedione
      monoxime (1 micromol/l) (ATP-sensitive K channel blockers) together completely
      blocked the relaxation response. [H]Ang II saturation binding at the AT2 receptor
      was enhanced in aortic membranes from diabetic [maximum binding capacity,
      (Bmax)=1.14 +/- 0.06 fmol/mg protein] compared to control rats (Bmax=0.75 +/-
      0.03 fmol/mg protein), with no change in the dissociation equilibrium constant
      (Kd) value (2.55 +/- 0.12 versus 2.22 +/- 0.15 nmol/l). CONCLUSIONS: The results
      suggest enhanced AT2-receptor density and function [mediated by a nitric oxide
      and ATP-sensitive K channel-dependent relaxation response (in presence of an AT1
      receptor blocker)] in thoracic aorta isolated from diabetic rats. This could be a
      compensatory mechanism, which may be therapeutically exploited.

PMID- 15480100
TI  - Glucose level is a major determinant of carotid intima-media thickness in
      patients with hypertension and hyperglycemia.
AB  - BACKGROUND: A causal relationship has been established between hyperglycemia and
      cardiovascular diseases, but no threshold has been retained to determine a
      'glycemia-associated' cardiovascular risk. Carotid intima-media thickness (CIMT)
      is an independent predictor for cardiovascular events. High blood pressure is a
      major determinant of CIMT. OBJECTIVES: To determine the influence of fasting
      glycemia on CIMT in hypertensive patients with either normal fasting glucose,
      impaired fasting glucose (IFG) or type 2 diabetes (DM-2). METHODS: We included
      158 essential hypertensive patients with either normal fasting glucose (n=74),
      IFG (n=24) or DM-2 (n=60) in a cross-sectional study. Common carotid IMT was
      measured with a high resolution echotracking system. RESULTS: CIMT of DM-2
      patients was significantly higher than that of IFG and normal fasting glucose
      patients (809 +/- 180, 697 +/- 151 and 689 +/- 134 microm, respectively; analysis
      of variance (ANOVA) P <0.0001). In multivariate analysis in normal fasting
      glucose patients, local pulse pressure and age were the major determinants of
      CIMT, whereas glycemia was not. In IFG and DM-2 patients, fasting glycemia was
      strongly associated with CIMT, explaining 21 and 18% of its variance,
      respectively. Particularly, in IFG patients, an increase in 1 mmol/l glycemia was
      associated with a 165 microm increase in CIMT. In hyperglycemic patients, with
      either IFG or DM-2, age was an important determinant of CIMT, whereas local pulse
      pressure was not. CONCLUSION: These data suggest that glycemia is a major
      independent determinant of CIMT in hypertensive hyperglycemic patients, not only
      in DM-2 patients but also at the earlier stage of IFG, offsetting the mechanical
      role of local pulse pressure.

PMID- 15480101
TI  - Time-dependent transition of tempol-sensitive reduction of blood pressure in
      angiotensin II-induced hypertension.
AB  - OBJECTIVE: Reactive oxygen species (ROS) participate in the intracellular
      signalling of angiotensin II. However, the mechanisms of the interaction of ROS
      with hypertension and mitogen-activated protein kinase (MAPK) in vivo have
      remained unclear. Angiotensin II infusion provokes sustained hypertension
      accompanied with enhancement of ROS production; initially hypertension is non
      sensitive to ROS, but thereafter becomes sensitive. We examined the time
      dependent transition of ROS-sensitive vasoconstriction during angiotensin II
      infusion and also ROS sensitivity to cardiovascular MAPK activation in acutely
      and chronically angiotensin II-infused rats. METHODS AND RESULTS: During infusion
      of a pressor dose of angiotensin II to conscious Sprague-Dawley rats, tempol, a
      superoxide dismutase mimetic, was administered at 10 min, some 1, 3, 6, 12 and 24
      h after the start of infusion. The magnitude of the reduction in blood pressure
      by tempol was initially negligible, but gradually enlarged, and reached a maximum
      of 96% of delta increase by angiotensin II at 12 h. However, even after
      sensitization to tempol, superimposed angiotensin II enabled an increase of blood
      pressure under tempol treatment. In chronically angiotensin II-infused rats,
      superimposed angiotensin II exhibited tempol quenchable MAPK activation.
      CONCLUSIONS: These results indicate that the mechanisms of angiotensin II-induced
      vasoconstriction may shift from being non-sensitive to ROS to sensitive within 12
      h; nevertheless, both ROS non-sensitive vasoconstriction and ROS-sensitive MAPK
      activation by angiotensin II, which are both seen in the acute phase of infusion,
      are restored in the late maintaining phase of prolonged angiotensin II infusion.

PMID- 15480102
TI  - Association of increased phagocytic NADPH oxidase-dependent superoxide production
      with diminished nitric oxide generation in essential hypertension.
AB  - OBJECTIVE: Oxidative stress has been implicated in the pathogenesis of
      hypertension and its complications through alterations in nitric oxide (NO)
      metabolism. This study was designed to investigate whether a relationship exists
      between phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      dependent superoxide anion (*O2-) production and NO generation in patients with
      essential hypertension. METHODS: Superoxide production was assayed by
      chemiluminescence under baseline and stimulated conditions on mononuclear cells
      obtained from hypertensives (n=51) and normotensives (n=43). NO production was
      evaluated by determining serum NO metabolites, nitrate plus nitrite (NOx).
      RESULTS: Although there were no differences in baseline *O2- production between
      normotensives and hypertensives, the *O2- production in phorbol myristate acetate
      (PMA)-stimulated mononuclear cells was increased (P <0.05) in hypertensives
      compared with normotensives. The PMA-induced *O2- production was completely
      abolished by apocynin, a specific inhibitor of NADPH oxidase. Moreover,
      stimulation of *O2- production by angiotensin II and endothelin-1 was higher (P
      <0.05) in cells from hypertensives than in cells from normotensives. In addition,
      diminished (P <0.001) serum NOx was detected in hypertensives compared with
      normotensives. Interestingly, an inverse correlation (r=0.493, P <0.01) was found
      between *O2- production and NOx in hypertensives. CONCLUSIONS: Generation of *O2-
      mainly dependent on NADPH oxidase is abnormally enhanced in stimulated
      mononuclear cells from hypertensives. It is suggested that this alteration could
      be involved in the diminished NO production observed in these patients.

PMID- 15480103
TI  - Divergent metabolic and vascular phenotypes in pre-eclampsia and intrauterine
      growth restriction: relevance of adiposity.
AB  - OBJECTIVE: Pre-eclampsia (PE) and intrauterine growth restriction (IUGR) may both
      arise secondary to inadequate trophoblast invasion. Maternal vascular disease is
      evident only in PE. Little mechanistic evidence exists to explain this dichotomy.
      METHODS: We employed laser Doppler imaging (LDI) to examine microvascular
      function in 15 women with PE and 30 healthy pregnant women matched for body mass
      index (BMI). We also examined 16 women with IUGR. Other factors examined included
      indices of inflammation, lipoproteins, leptin and insulin concentrations.
      RESULTS: Women with PE had double the concentration of leptin and 30% higher
      triglyceride than controls. Vascular cell adhesion molecule (VCAM)-1 and
      interleukin (IL)-6 were also higher in women with PE, with both factors
      correlating with leptin independently of BMI. No difference in microvascular
      reactivity was observed between controls and women with PE. Women with IUGR had a
      four-unit smaller BMI than women with PE. When compared with controls, they also
      had lower low-density lipoprotein cholesterol (LDL-C) concentrations and systemic
      inflammatory measures were not elevated. CONCLUSIONS: The technique of LDI is not
      sensitive to the vascular dysfunction of PE. However, circulating endothelial
      derived factors are elevated in association with markedly elevated leptin levels.
      Therefore, women with IUGR may demonstrate a protective role for their 'leanness'
      with regard to maternal systemic inflammatory effect.

PMID- 15480104
TI  - Glomerular number and size in Milan hypertensive and normotensive rats: their
      relationship to susceptibility and resistance to hypertension and renal disease.
AB  - OBJECTIVE: Structural analysis, including morphometric computation of glomerular
      size and number, was applied to analyse the divergence between propensity to
      hypertension and renal damage, expressed by rats of the Milan hypertensive strain
      (MHS) and Milan normotensive strain (MNS), respectively. DESIGN: MHS, MNS rats
      and progenitor Wistar rats were investigated at age 9 weeks and 9 months.
      Classical morphometric methods were complemented by the dissector/fractionator
      technique to count glomeruli. RESULTS: At 9 weeks, when nephrogenesis was
      completed and hypertension established, MHS rats exhibited significantly lower
      kidney weight, cortical volume, glomerular number and volume compared to coeval
      MNS rats. In Wistar rats, these parameters were similar to those of MNS rats,
      except for lower glomerular volume. At 9 months, MHS rats showed significantly
      lower expansion of glomerular volume compared to MNS and Wistar rats. MNS rats
      had 10% sclerotic glomeruli, which was associated with reduced renal function and
      heavy proteinuria; conversely, sclerosis was rare in coeval MHS and Wistar rats.
      Media thickness was higher, whereas lumen diameter was lower, in intrarenal
      arteries of MHS versus MNS rats at both time points. CONCLUSIONS: These data
      indicate that structural changes other than a tubular defect may play a role in
      the development of hypertension in MHS rats. The lack of significant glomerular
      hypertrophy and damage in this strain, despite reduced glomerular number, could
      be related to their (haemodynamic) protection from hypertensive renal disease,
      possibly due to the hypertrophy of intrarenal arteries. The larger size of
      glomeruli of MNS rats may be linked to their susceptibility to
      glomerulosclerosis.

PMID- 15480105
TI  - Exercise versus recovery electrocardiography for predicting outcome in
      hypertensive patients with chest pain.
AB  - BACKGROUND: Exercise electrocardiography has limited prognostic accuracy in
      hypertensives because of unsatisfactory specificity. We prospectively used
      comparative stress-recovery heart rate-adjusted ST (ST/HR) analysis to predict
      mortality in a consecutive population of hypertensives with chest pain. METHODS:
      The stress-recovery index (SRI), defined as the difference between ST/HR areas
      during exercise and recovery, was derived in 460 hypertensive with known (n=360,
      78%) or suspected (n=100, 22%) coronary artery disease. To assess whether it
      added prognostic information to routinely obtained information, clinical data,
      the resting ejection fraction, and exercise testing data were entered into a
      sequential Cox's model; the SRI was entered last. Model validation was performed
      by bootstrap adjusted by the degree of optimism in estimates. Survival analysis
      was performed using the product-limit Kaplan-Meier method. RESULTS: During a
      median follow-up of 28 months (interquartile range, 13-44 months), 32 (7%)
      patients died, 23 (5%) suffered from acute myocardial infarction and 60 (13%)
      underwent late (> 3 months) revascularization. Male gender (hazard ratio, 1.53;
      95% confidence interval, 1.01-2.34), peak double product (hazard ratio, 0.70; 95%
      confidence interval, 0.54-0.90) and the SRI (hazard ratio, 0.69; 95% confidence
      interval, 0.59-0.81 for interquartile difference) were independent predictors of
      outcome. The SRI increased the prognostic power of the model on top of clinical
      and exercise testing variables (concordance index, + 10%; discrimination index, +
      32%) and showed the widest area under the ROC curve to predict outcome as
      compared with exercise-only ST analysis and the ST/HR index. Moreover, it
      provided a significant discrimination of survival. CONCLUSIONS: The SRI predicts
      all-cause mortality in hypertensive patients with chest pain and provides
      additional prognostic information over clinical and standard exercise testing
      data.

PMID- 15480106
TI  - Nebivolol improves coronary flow reserve in hypertensive patients without
      coronary heart disease.
AB  - OBJECTIVE: To examine the effects of nebivolol, a beta-blocker with nitroxide
      mediated vasodilating properties, on coronary flow reserve (CFR) in patients with
      uncomplicated arterial hypertension. DESIGN, SETTING AND PATIENTS: Fourteen newly
      diagnosed, never-treated, World Health Organization grade I-II hypertensive
      patients (male/female, 10/4; mean age, 47 years), free of coronary heart disease,
      underwent standard Doppler echocardiography and determination of CFR in the
      distal left anterior descending artery by low-dose dipyridamole (0.56 mg/kg
      intravenously in 4 min) at baseline and after 4 weeks of treatment with 5 mg
      nebivolol once daily. RESULTS: At baseline, nine patients had left ventricular
      (LV) hypertrophy (LV mass index > or = 51 g/m). After 4 weeks of therapy, the
      blood pressure was decreased from 148 +/- 8.1/101.4 +/- 4.6 mmHg to 140.7 +/-
      7.0/91.1 +/- 7.4 mmHg and end-systolic stress was also significantly reduced.
      Heart rate was reduced (P <0.01), whereas LV end-diastolic diameter and stroke
      volume tended to increase (P=0.07 and P=0.09, respectively). No changes were
      detected in the LV mass index, relative wall thickness, fractional shortening and
      LV diastolic properties. Both resting and dipyridamole rate-pressure products
      were lower after nebivolol but dipyridamole-induced changes were not influenced
      by the therapy. In contrast, nebivolol therapy did not alter coronary velocities
      at rest, but caused a greater increase in coronary velocities after dipyridamole
      (P <0.03), leading to a greater CFR (2.12 +/- 0.33 versus 1.89 +/- 0.31, P
      <0.0001). Nebivolol induced an absolute increase of 8% in the CFR in nine of 14
      patients (64.3%). CONCLUSIONS: In hypertensive patients free of coronary artery
      disease, 4-week nebivolol therapy induces a significant increase of the CFR.
      Nebivolol preserves coronary flow at rest despite the reduction of metabolic (O2
      consumption) and hemodynamic (diastolic blood pressure) determinants. The
      increase of hyperemic coronary velocities appears due to the reduction of
      coronary resistance.

PMID- 15480107
TI  - Does comorbidity explain trends in prescribing of newer antihypertensive agents?
AB  - OBJECTIVE: Concerns exist about heavily prescribing of new drugs when the
      evidence on hard outcomes is still limited. This has been the case for the newer
      classes of antihypertensives, especially in hypertensive patients without
      additional comorbidity. The association between comorbidity and trends in
      prescribing of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin
      II receptor blockers (ARBs) was examined for the period 1996-2000. DESIGN AND
      METHODS: Data were obtained from the Integrated Primary Care Information
      database, which contains medical records from more than 100 general practitioners
      in the Netherlands. Prevalent drug use in hypertensive patients was determined
      per calendar year. As initial treatment, the first antihypertensive drug
      prescribed within 1 year after diagnosis of hypertension was considered. Logistic
      regression was used to estimate the likelihood of receiving either ACE-I or ARBs.
      RESULTS: The overall prevalent ACE-I use remained stable (31%), but it increased
      from 33 to 41% in hypertensive patients with diabetes, heart failure, proteinuria
      and/or renal insufficiency. ARB use increased significantly from 2 to 12%; this
      trend did not differ between patients with or without specific comorbidities.
      Initial ACE-I use slightly decreased (from 29% to 24%), whereas initial ARB use
      significantly increased (from 4% to 12%). ACE-I were more likely to be the first
      treatment in patients with diabetes [odds ratio (OR)=3.9; 95% confidence interval
      (CI) 3.2-4.9] or hypercholesterolemia (OR=1.4; 95% CI 1.1-1.8). ARBs were more
      likely to be the initial treatment in patients with asthma/chronic obstructive
      pulmonary disease (OR=1.6; 1.2-2.3), diabetes (OR=2.1; 1.5-2.9) or
      hypercholesterolemia (OR=1.7; 1.2-2.4). CONCLUSIONS: The increased use of ACE-I
      is mostly restricted to hypertensive patients with comorbidities for which their
      use has been recommended. Trends in prescribing of ARBs are not related to
      relevant comorbidities.

PMID- 15480110
TI  - Hypertension in children and adolescents.

PMID- 15480108
TI  - Low-renin status in therapy-resistant hypertension: a clue to efficient
      treatment.
AB  - OBJECTIVE: Therapy resistance is an enduring problem in clinical hypertension.
      Our aims were to estimate: (1) the contribution of a low-renin status in therapy
      resistance; (2) whether such status could give a clue to more successful
      treatment; and (3) the contribution by adrenal cortical adenomas and by primary
      aldosteronism. SETTING: Patients were referred from general and internal medicine
      practices following written invitations and included consecutively. Participants
      were examined and followed-up on an outpatient basis. DESIGN AND INTERVENTIONS:
      Patients were divided according to renin status. Low-renin patients were treated
      with an aldosterone inhibitor in a prospective, randomized, placebo-controlled,
      double-blind, cross-over study. MAIN OUTCOME MEASURES: Prevalence of low-renin
      status in therapy resistance. Blood pressure and hormonal responses to specific
      treatment. Numbers of adrenocortical adenomas and primary aldosteronism. RESULTS:
      In 90 treatment-resistant hypertensive, 67% had plasma renin activity (PRA) below
      0.5 nmol/l per hour. Of the 60 low-renin patients, 38 were studied on a fixed
      combination of amiloride and hydrochlorothiazide. Three weeks' treatment reduced
      blood pressure by 31/15 mmHg compared to placebo (P < or = 0.0001). Serum
      aldosterone and plasma renin activity increased substantially during active
      treatment. Through the subsequent 6-12 months of open treatment, seven patients
      (18%) showing an escape phenomenon had their high blood pressure effectively
      treated by extra amiloride. Of the 60 low-renin patients, eight had adrenal
      adenoma. CONCLUSION: A low-renin status characterized two-thirds of patients with
      treatment-resistant hypertension, who could be treated efficiently by aldosterone
      inhibition. Patients with an escape phenomenon (18%) could effectively be treated
      by increasing the aldosterone inhibitor. Low-renin hypertensives had high
      prevalence of adrenocortical adenomas and primary aldosteronism.

PMID- 15480111
TI  - The psychosocial impact of testing individuals with no history of genital herpes
      for herpes simplex virus type 2.
AB  - BACKGROUND: Although approximately 20% of the population has a genital herpes
      (HSV-2) infection, 80% of these infections are unrecognized or asymptomatic.
      Serologic identification of HSV-2 leads to recognition of infection, which could
      lead to behavioral changes that reduce transmission. However, there has been
      concern that HSV-2 testing among persons without symptoms will cause substantial
      psychosocial harm. GOAL: The goal of this study was to assess the psychosocial
      impact of an HSV-2 diagnosis among individuals without a history of genital
      herpes attending a sexually transmitted disease (STD) clinic. STUDY: We conducted
      a cohort study of persons with no history of genital herpes attending an STD
      clinic and seeking herpes testing. Two follow-up interviews were conducted 1 week
      and 3 months after persons received their test results. Serum was tested using
      HerpeSelect 2. Psychosocial morbidity was assessed at baseline and each follow up
      using a mental health score, sexual attitude score, and perception of genital
      herpes score. RESULTS: Twenty-one percent (41 of 196) of participants tested
      positive for HSV-2 antibody. Among patients who were HSV-2-positive, there was no
      significant change in mental health score from baseline during either follow-up
      visit, nor was there any difference compared with persons who were HSV-2
      negative. Patients who were HSV-2-positive did have a decline (P = 0.01) in their
      sexual attitude scores at the 1-week follow up compared with persons who were HSV
      2-negative, indicating a decrease in positive sexual attitude, but this
      difference no longer remained at the 3-month follow up (P = 0.74). Patients who
      were HSV-2-positive viewed having genital herpes as significantly less traumatic
      than patients who were HSV-2-negative at both follow-up visits (P <0.01).
      CONCLUSION: There was no apparent lasting adverse psychosocial impact of
      detecting HSV-2 infection among individuals without a history of genital herpes
      seeking herpes testing at an STD clinic.

PMID- 15480112
TI  - Changing patterns in sexually transmitted disease syndromes in Kenya after the
      introduction of a syndromic management program.
AB  - OBJECTIVE: The objective of this study was to evaluate patterns in sexually
      transmitted disease (STD) syndromes after the introduction of an STD syndromic
      management program. STUDY: We used the HIV sentinel surveillance in patients with
      STDs (1990-2001) to compute the proportions of STD syndromes (as a proportion of
      all patients with STDs) before and after the introduction of the syndromic
      management program. RESULTS: A decline in the proportion of genital ulcer disease
      (GUD), urethral discharge (UD), and vaginal discharge (VD) was observed from the
      baseline (1990-1994) to the year 2000 (P <0.0001). GUD declined from 27.6% at
      baseline to 11.0% in 2000; UD from 31.8% at baseline to 22.2% in 2000; and VD
      from 36.7% at baseline to 20.1% in 2000. Similar declines for these syndromes
      were also observed in sex and age groups. The proportions of GUD, UD, and UV
      increased again in 2001. CONCLUSIONS: These changing patterns of STD syndromes
      were coincident with the introduction of the STD syndromic management program in
      1995 and the termination of free STD medication in 2001.

PMID- 15480113
TI  - Comparison of sexually transmitted disease prevalence by reported condom use:
      errors among consistent condom users seen at an urban sexually transmitted
      disease clinic.
AB  - BACKGROUND: The protective effect of condom use is controversial as a result of
      limited data. GOAL: The goal of this study was to assess the association between
      condom use errors in consistent condom users and the prevalence of various
      sexually transmitted diseases (STDs). STUDY: We conducted a cross-sectional study
      of visits to an urban STD clinic between January 2001 and January 2003, by women,
      men who have sex with women (MSW), and men who have sex with men (MSM) by
      consistent condom users with or without a condom use error. METHODS: Prevalence
      rates were calculated for gonorrhea, chlamydia, trichomonas, nongonococcal
      urethritis (NGU), and pelvic inflammatory disease. Rates were stratified by
      reported errors in condom use over the past 4 months for consistent users with
      adjusted odds ratios calculated by logistic regression. RESULTS: Among 1973
      consistent condom users with error information available, any condom use error
      was reported more commonly among women (57%) than MSW (48%), or MSM (P <0.001 for
      each comparison), with breakage being the most frequently reported error. Among
      MSW, having a condom use error was associated with gonorrhea (adjusted odds ratio
      [AOR], 5.53; 95% confidence interval [CI], 2.48-12.35), chlamydia (AOR, 3.19; 95%
      CI, 1.80-5.65), and NGU (AOR, 2.09; 95% CI, 1.45-3.01), whereas, for women and
      MSM, no associations were seen for any STD. CONCLUSIONS: Condom use errors were
      common among subjects reporting consistent condom use and for MSW, condom error
      was associated with a significant increased risk of STD. These data support the
      premise that correctness of condom use is an important methodologic issue in
      studies assessing condom effectiveness.

PMID- 15480114
TI  - Family socioeconomic status and self-reported sexually transmitted diseases among
      black and white american adolescents.
AB  - OBJECTIVE: The objective of this study was to assess associations between
      socioeconomic status (SES) and adolescent sexually transmitted diseases (STDs)
      stratified by race and gender. STUDY: In cross-sectional analyses of the National
      Longitudinal Study of Adolescent Health Wave One (1995), unadjusted and adjusted
      associations between 4 family SES indicators and STD reports for black and white
      7th through 12th graders were examined. RESULTS: Lower maternal education and
      nonprofessional maternal occupations were associated with higher STD reports in
      all groups except white females. Generally, STD reports were higher for
      adolescents not living in 2-parent homes, and lower income was only associated
      for black males. CONCLUSION: Overall, SES is only a weak to moderate marker for
      adolescent STD risks. The relationship of SES and STDs varies by the SES measure
      used and differs across race-gender groups. Other individual factors such as risk
      behaviors or community factors such as income inequality could play a more
      critical role for adolescent STDs than family SES.

PMID- 15480115
TI  - Prevalence and risk behaviors for chlamydial infection in a population-based
      study of female adolescents in Brazil.
AB  - BACKGROUND: Adolescents are vulnerable to sexually transmitted infections (STIs)
      and unplanned pregnancy. Prevention measures and assistance are of significant
      public health importance in this population. OBJECTIVE: The objective of this
      study was to identify demographic, behavioral, and clinical factors for STIs and
      to determine the prevalence of Chlamydia trachomatis infection (CT) among female
      adolescents in Vitoria, Brazil. METHODS: We performed a cross-sectional study
      among female adolescents (15-19 years) served by the Health Family Program.
      Participants were screened for CT and Neisseria gonorrhoeae (GC) using ligase
      chain reaction applied to urine and answered a face-to-face questionnaire to
      assess demographic, behavioral, and clinical factors. All participants and their
      parents signed the informed consent. RESULTS: Four hundred sixty-four young women
      were sampled. The prevalence of CT was 8.9% (95% confidence interval [CI], 6.5
      11.9%) overall. Among sexually active women, CT and gonorrhea prevalence were
      12.2 (95% CI, 9.4-17.0%) and 1.9% (95% CI, 1.1-2.7%), respectively. Previously
      diagnosed STI was reported by 12.8%. Women who reported regular condom use and
      having condoms at home were significantly less likely to have CT, and having
      never purchased condoms was significantly associated with a positive CT result.
      CONCLUSION: A high prevalence of CT was found in this population, and behavioral
      risk was high despite readily available STI prevention information. Women who
      reported positive condom use behaviors were less likely to have CT. These results
      demonstrate the need for ongoing STI prevention activities, including STI
      screening and continued successful risk reduction activities such as condom use
      to further decrease CT and other STI among adolescents.

PMID- 15480116
TI  - Estimates of the annual number and cost of new HIV infections among women
      attributable to trichomoniasis in the United States.
AB  - BACKGROUND: Clinical evidence suggests that trichomoniasis facilitates the sexual
      transmission and acquisition of HIV. GOAL: The goal of this study was to estimate
      the annual number and cost of new HIV infections among women in the United States
      attributable to trichomoniasis. STUDY: We used a mathematical model of HIV
      transmission to estimate the probability that a woman with trichomoniasis would
      acquire HIV as a result of her trichomoniasis-mediated increased susceptibility
      to HIV infection or as a result of increased HIV infectiousness in a
      trichomoniasis-infected male partner. RESULTS: Our results indicate that each
      year in the United States, an estimated 746 new HIV cases among women can be
      attributed to the facilitative effects of trichomoniasis on HIV transmission. The
      lifetime cost of treating these trichomoniasis-attributable HIV infections is
      approximately $167 million. CONCLUSIONS: Efforts to prevent trichomoniasis could
      help prevent HIV transmission and could reduce the economic burden associated
      with trichomoniasis-attributable HIV cases that occur each year. Because
      trichomoniasis is so common, however, a substantial number of cases would need to
      be detected and treated to have a discernible impact on HIV. Future research is
      needed to examine the cost-effectiveness of trichomoniasis prevention as a tool
      for HIV prevention.

PMID- 15480117
TI  - Correlates of Internet use to meet sex partners among men who have sex with men
      diagnosed with early syphilis in Los Angeles County.
AB  - OBJECTIVE: The objective of this study was to evaluate use of the Internet to
      solicit sex partners by men who have sex with men (MSM) who were diagnosed with
      early syphilis infection. STUDY: Field interview records for syphilis patients
      were reviewed for factors associated with Internet use. RESULTS: Internet users
      were more likely to be of white race (prevalence ratio [PR], 1.6; 95% confidence
      interval [CI], 1.4-1.8), to report anal insertive sex (PR, 1.1; 95% CI, 1.1-1.2),
      sex with anonymous partners (PR, 1.2; 95% CI, 1.1-1.3), intravenous drug use (PR,
      2.7; 95% CI, 1.1-6.7), and nonintravenous drug use (PR, 1.4; 95% CI, 1.1-1.8).
      Controlling for race and sexual risk behaviors, white race (odds ratio [OR], 2.8;
      95% CI, 1.8-4.6), having anonymous sex partners (OR, 3.4; 95% CI, 1.6-7.0), and
      nonintravenous drug use (OR, 1.6; 95% CI, 1.1-2.6) were associated with meeting
      sex partners through the Internet. CONCLUSIONS: Effective sexually transmitted
      disease risk reduction interventions using the Internet are needed to reach
      Internet-using, sex-seeking MSM populations engaging in high-risk behaviors.

PMID- 15480119
TI  - Hormonal contraceptive use, cervical ectopy, and the acquisition of cervical
      infections.
AB  - BACKGROUND AND OBJECTIVES: Several previous studies have suggested that hormonal
      contraception could be associated with increased risk of cervical infections.
      However, few high-quality prospective studies have examined this relationship.
      GOAL: The goal of this study was to measure the effect of oral contraceptives
      (OC) and depot-medroxyprogesterone acetate (DMPA) on the acquisition of cervical
      chlamydial and gonococcal infections. STUDY: Women attending 2 reproductive
      health centers in Baltimore, MD, were enrolled into a prospective cohort study.
      Participants were 15 to 45 years and were initiating OCs or DMPA or not using
      hormonal contraception. Interviews, physical examinations, and testing for
      incident cervical infections were conducted at 3, 6, and 12 months. RESULTS: The
      analysis included 819 women. Most were single (77%) and nulliparous (75%); 43%
      were black. Median age was 22 years. During the study, 45 women acquired a
      chlamydial or gonococcal infection (6.2 per 100 women-years). DMPA use (hazard
      ratio [HR], 3.6; 95% confidence interval [CI], 1.6-8.5), but not OC use (HR, 1.5;
      95% CI, 0.6-3.5), was significantly associated with increased acquisition of
      cervical infections after adjusting for other risk factors. Cervical ectopy was
      not an important mediator of cervical infection risk. CONCLUSIONS: DMPA use, but
      not OC use, appeared to be significantly associated with increased acquisition of
      cervical chlamydial and gonococcal infections.

PMID- 15480118
TI  - Performance of rapid syphilis tests in venous and fingerstick whole blood
      specimens.
AB  - OBJECTIVE: Rapid syphilis screening could facilitate case-identification during
      U.S. outbreaks. GOAL: The goal of this study was to determine the performance of
      3 rapid syphilis tests in whole blood specimens in the laboratory and in patients
      at a sexually transmitted disease (STD) clinic. STUDY: We tested whole blood
      samples from STD clinic patients with 3 rapid tests and compared results with the
      serum treponemal pallidum particle agglutination (TP-PA) test. We evaluated the
      best performing of the 3 rapid tests on fingerstick specimens from STD clinic
      patients. RESULTS: The Abbott Determine TP (n = 127) had the highest sensitivity
      (88%; 95% confidence interval [CI], 81-96%) and lowest rate of indeterminate
      tests (0.8%), followed by Guardian Biosciences One Step (n = 116) (sensitivity
      72%; 95% CI, 60-84%; indeterminate 6.5%), and Phoenix Biotech Trep-Strip IV (n =
      71) (sensitivity 70%; 95% CI, 54-85%; indeterminate 30.3%). All 3 tests were 100%
      specific. The Abbott Determine TP showed excellent performance on fingerstick
      specimens (n = 99), exhibiting 100% sensitivity (95% CI, 93-100%), 100%
      specificity, and 2.9% indeterminate. CONCLUSIONS: The Abbott Determine TP test
      was an easy and accurate test that could facilitate rapid detection of syphilis
      in at-risk patients.

PMID- 15480120
TI  - Prevalence and risk behaviors of Hong Kong males who seek cross-border same-sex
      partners in mainland China.
AB  - BACKGROUND: Little is known about cross-border sex-networking behaviors among men
      who have sex with men (MSM) GOAL: The goal of this study was to determine the
      prevalence of cross-border sex-networking in mainland China among MSM in Hong
      Kong and the associated risk behaviors STUDY: A telephone survey was conducted. A
      total of 15,230 Hong Kong Chinese men aged 18 to 60 participated in the study.
      RESULTS: Of the 283 MSM engaged in some MSM behaviors in the last 6 months, 15.2%
      had engaged in sexual activity with a man in mainland China in the 6 months
      before the survey. These "cross-border MSM" were more likely than others to have
      practiced risk behaviors such as having patronized male commercial sex workers,
      having contracted a sexually transmitted disease (STD), having had > or = 3 MSM
      partners, and having higher prevalence of HIV testing in the last 6 months
      (adjusted odds ratio, 3.32-43.83). CONCLUSIONS: There is an urgent need for a
      regional approach to HIV/STD prevention for MSM in southern China.

PMID- 15480121
TI  - Risk perceptions, condom use, and sexually transmitted diseases among adolescent
      females according to social network position.
AB  - BACKGROUND AND OBJECTIVES: Adolescent females are frequently treated as a
      homogenous group but could differ on their sexually transmitted disease (STD)
      risk because of individual attitudes and exposure through sexual networks. GOAL:
      The goal of this study was to determine if risk perceptions, condom use, and STD
      prevalence differs within sexual networks. STUDY DESIGN: Three hundred three
      adolescent females participating in a longitudinal study of adolescent STD risk
      perceptions and condom use were categorized as "core," "bridge," and "periphery"
      in a sexual network according to their and their main sex partner's risk
      information. Regression analysis determined differences in risk perceptions by
      network location. RESULTS: We demonstrated an inverse relationship between STD
      risk perceptions and network location. Adolescents with higher risk perceptions
      were more likely to use condoms, irrespective of network location. CONCLUSION:
      Female adolescents are a heterogeneous group exhibiting different risk
      perceptions. Different intervention strategies for adolescents at higher risk
      could be necessary. Interventions designed to raise risk perceptions could be
      associated with condom use, even for those adolescents at greatest risk.

PMID- 15480122
TI  - Seated postural control in adolescents with idiopathic scoliosis.
AB  - STUDY DESIGN: The center of pressure (COP) path in 14 adolescents with idiopathic
      scoliosis and 12 age-matched able-bodied adolescents was compared using
      traditional measures and a two-level decomposition. OBJECTIVES: To investigate
      whether asymmetries in the spines of children with idiopathic scoliosis are
      reflected in altered sway patterns in quiet sitting. SUMMARY OF BACKGROUND DATA:
      Previous studies have studied the sway of children with scoliosis while standing.
      However, the standing posture is typically controlled at the ankle joint. To
      date, there are no studies with this population of sitting sway, where the
      movement is controlled by the trunk muscles. METHODS: Traditional measures of the
      COP of the trunk were analyzed. The COP was also decomposed into an approximation
      of the center of mass path and deviations around this path. RESULTS: COP movement
      in sitting, reflecting the postural control of the spine, was decreased in
      adolescents with idiopathic scoliosis. Children with scoliosis had symmetric
      sitting COP trajectories and most measures were similar between the two groups.
      CONCLUSIONS: The results suggest a control strategy for maintaining a sitting
      posture that does not change with the development of scoliosis but does adapt by
      decreasing movement to maintain the trunk in a region where the it can remain
      "passively" stable.

PMID- 15480123
TI  - Vertebral wedging characteristic changes in scoliotic spines.
AB  - STUDY DESIGN: A morphometric analysis of vertebral wedging in vertebrae from
      scoliotic specimens. OBJECTIVE: To quantify the vertebral body changes in 30
      anatomic specimens affected by a scoliotic deformity. SUMMARY OF BACKGROUND DATA:
      Only a few studies have evaluated the exact changes occurring at the level of the
      vertebral body in scoliotic spines. Most are observational studies of rare
      scoliotic specimens presenting major curvatures. The orientation of vertebral
      wedging is important for the planning of corrective surgery, performing vertebral
      osteotomy, and the evaluation of possible growth modulation. MATERIALS AND
      METHODS: Thirty scoliotic specimens with curves presenting various degrees of
      severity were studied using a three-dimensional digitizing protocol developed to
      create a precise three-dimensional reconstruction of the vertebrae. Every
      scoliotic specimen was then matched with a normal specimen, and comparisons were
      made on the vertebral body parameters both for thoracic and lumbar vertebrae.
      Analysis of variance and t test calculations were performed to identify
      significant differences with P = 0.05. RESULTS: A total of 471 vertebrae from
      scoliotic spines and 510 vertebrae from normal specimens were measured. Vertebral
      wedging increased progressively towards the apex of the curve and was maximal at
      the apex. Vertebral wedging was more prominent in the frontal plane, and there
      was minimal wedging in the sagittal plane. Vertebral heights were significantly
      different at T3 and T4 for the upper adjacent curve and at T6-T8 for a typical
      right thoracic curve, with smaller heights located on the concavity of the curve.
      No changes were observed on the convexity of the curve. CONCLUSION: Vertebral
      wedging is an essential component of the scoliotic deformity. The present study
      provides critical information for corrective surgery and vertebral osteotomy, as
      vertebral wedging occurs primarily in the frontal plane. Accurate knowledge of
      this deformity should also provide new insight into corrective surgical
      strategies aiming at growth modulation and more efficient surgical correction.

PMID- 15480124
TI  - Intradural disc herniation and epidural gas: something more than a casual
      association?
AB  - STUDY DESIGN: The case of a patient with an intradural disc herniation associated
      with gas in the spinal canal is presented. OBJECTIVE: To alert spine surgeons to
      this potential association. SUMMARY OF BACKGROUND DATA: This association was
      described previously in five patients, a fact that seems surprising given the
      relative rarity of both intraspinal gas and intradural herniations. METHODS: The
      case is presented of a female patient with lumbosciatic pain who developed an
      incomplete cauda equina syndrome. An asymmetric discopathy of the L2-L3 space and
      a gas bubble with disc material within the spinal canal was noticed in the
      radiologic explorations. The literature and the authors' experience are reviewed
      with the aim of confirming the frequency of intradural herniation in association
      with gas in the spinal canal. RESULTS: A laminoarthrectomy of the involved space
      was performed followed by direct intradural examination, which revealed a disc
      fragment that was excised. An instrumented L2-L3 arthrodesis was performed.
      Postoperative evolution was satisfactory. To date, the authors have found this
      association in 2% of the patients with intraspinal gas. CONCLUSION: The potential
      presence of an intradural disc herniation must always be considered when
      performing an open discectomy on a patient whose CT scan study shows the presence
      of epidural gas. This association is particularly striking given the relative
      rarity of intradural herniations and intraspinal gas. In the event that no clear
      disc herniation was found, an intradural examination may be indicated to justify
      clinical signs and symptoms or previous radiologic studies.

PMID- 15480125
TI  - Back pain and health policy research: the what, why, how, who, and when.
AB  - STUDY DESIGN: A background literature, supported by discussion and outcomes on
      the subject of Health Policy and Back Pain, from the Fifth International Forum on
      Low Back Pain Research in Primary Care, in Montreal in May 2002. SUMMARY OF
      BACKGROUND DATA: A multitude of randomized controlled trials and systematic
      reviews have been completed in the field of back pain research. There has been
      limited health policy research in the field of back pain but a greater amount of
      health policy research in other medical fields. METHODS: The focus of the
      workshop was on the contribution health policy could make in the area of back
      pain, the methodologies that are appropriate to research in back pain, and the
      barriers to back pain health policy research. The workshop was supported by the
      workshop coordinators' literature review. RESULTS: There was consensus about the
      lack of improved outcomes from randomized controlled trials and individual
      treatments and general agreement on the importance supporting current research
      initiatives with health policy research. That policy-makers were developing
      policy in this area was agreed, and study methodology to support evidence based
      policy development was explored. CONCLUSIONS: Health policy research is a
      relatively underdeveloped area of research in back pain. Back pain as a public
      health problem may be supported by a broader research approach and a
      collaborative association with policy-makers in this area.

PMID- 15480126
TI  - The "human tail": a rare cause of tethered cord: a case report.
AB  - STUDY DESIGN: Observational case report. OBJECTIVES: To report a case of dorsal
      cutaneous appendage or the so-called human tail that was the cause of tethered
      cord syndrome. SUMMARY OF BACKGROUND DATA: The dorsal cutaneous appendage, or so
      called human tail, is often considered to be a cutaneous marker of underlying
      occult spinal dysraphism. In such cases, there is usually a separate underlying
      tethering lesion. There have been only three case reports in the literature where
      this appendage itself was the tethering lesion. The fourth such case is being
      reported. METHODS: An 11-month-old male child was brought for consultation for a
      "tail-like" structure in the low back since birth. Examination revealed a subtle
      thinning of the right lower extremity and a caudal appendage in the lower lumbar
      region. Plain radiographs revealed spina bifida at S1. MRI revealed a
      transitional lipoma at L5-S1 with a terminal syrinx. RESULTS: During surgery, a
      fibrous tract was seen extending from the base of the appendage through the
      defect in the bone and dura. The tract ended in the transitional lipoma of the
      cord at L5-S1. Sectioning of the tract and debulking of the transitional lipoma
      was done. After surgery, there was no change in the neurologic status of the
      patient. CONCLUSIONS: This case illustrates that the so-called "human tail" or
      the dorsal cutaneous appendage is not just a marker of underlying occult spinal
      dysraphism. In rare cases, the appendage itself can be the tethering lesion. In
      every case of dorsal cutaneous appendage, the surgeon should diligently search
      for the intraspinal extension of the lesion even if such an extension is not
      revealed by the MRI.

PMID- 15480128
TI  - A randomized clinical trial of treatment for lumbar segmental rigidity.
AB  - STUDY DESIGN: A randomized single-blind clinical trial of facet injections plus
      exercise, versus exercise alone, in chronic disabling work-related lumbar spinal
      disorders (CDWRLSD), accompanied by pilot interrater reliability and facet
      syndrome prevalence studies. OBJECTIVES: To systematically investigate the use of
      facet injections as an adjunct to supervised lumbar stretching exercises in
      regaining lumbar range of motion (ROM) following prolonged deconditioning after
      work-related lumbar injuries. To assess interrater reliability of visual
      assessment of segmental rigidity (SR), and to evaluate the prevalence of facet
      syndrome in cases of lumbar SR. SUMMARY OF BACKGROUND DATA: Corticosteroid joint
      injections have often been used to reduce musculoskeletal inflammation to
      facilitate joint mobilization in the presence of degenerative arthritis. Lumbar
      segmental rigidity is a recently described entity usually associated with painful
      chronic spinal disorders and postoperative spine surgery. Previous work has shown
      that SR and lumbar ROM improves with a brief intervention consisting of facet
      injections followed by specific stretching exercises. No systematic study has
      investigated the potential benefits of a combination of facet injections and
      exercise over supervised exercises alone to treat lumbar SR. Similarly, no study
      has assessed the association between SR and the facet syndrome. METHODS: From a
      group of consecutive patients (n = 421) with CDWRLSD referred for tertiary
      rehabilitation between November 1999 and January 2001, 70 were noted to have SR
      on intake physical examination. The first part of this study assessed interrater
      reliability for detecting SR, and intrarater reliability for 3-segment true
      lumbar ROM measurements. Patients randomly assigned to participate in supervised
      stretching exercises with the addition of fluoroscopically guided bilateral facet
      injections at the involved levels (Group A, n = 36) also underwent facet syndrome
      prevalence assessment at the time of injection. They were compared to a randomly
      allocated comparison group (Group B, n = 34) undergoing exercises alone in a
      single-blind design. Physical therapists saw patients an average of twice per
      week, providing supervision of a progressive home stretching program.
      Inclinometric joint ROM was measured at the time of group allocation, and again 5
      to 7 weeks later. Validated questionnaires of pain (intensity VAS) and disability
      (Million VAS) related to the CDWRLSD were provided before and after the
      interventions. RESULTS: Part 1 reliability and facet syndrome prevalence work
      revealed that interrater reliability for experienced examiners to detect rigid
      segments was excellent (Pearson's r = 0.97, P < 0.01). Intrarater 3-joint motion
      measurement reliability was also good for all sagittal/coronal ROM (Pearson's r =
      0.95-0.99, P < 0.01). Only 5 of 29 subjects with SR met criteria for facet
      syndrome (17%), consistent with prior prevalence studies of unselected patients
      with low back pain. In Part 2, a large majority of patients in both groups
      improved from the initial to the post-treatment ROM measurements (the primary
      outcome criterion of the study). However, a higher proportion of Group A
      (injection) patients (87%-95%) showed ROM improvement, compared to Group B
      (exercise only) patients (64%-79%). Group A patients showed a significantly
      greater ROM improvement in all sagittal and coronal movements, both in absolute
      terms and percent of initial measurement. No significant differences in pain or
      disability self-report were found between groups, pre- or postintervention, but
      both groups showed significant improvement from pre- to postintervention in pain
      and disability assessments. CONCLUSIONS: The detection of SR and measurement of 3
      segment true lumbar ROM by experienced examiners is highly reliable. Only 17% of
      CDWRLSD patients with lumbar SR met criteria for the facet syndrome, a rate
      approximately equal to that of unselected low back pain cohorts. This indicates
      that lumbar SR may be found whether or not pain of facet joint origin is present.
      In the randomized trial, facet injections significantly increased the percentage
      of patients with SR showing ROM improvement, as well as the degree of improvement
      in lumbar mobility after treatment. There is no evidence that facet injections
      increase the improvements in pain/disability report noted in both groups.

PMID- 15480130
TI  - A randomized clinical trial of manipulative therapy and interferential therapy
      for acute low back pain.
AB  - STUDY DESIGN: A multicenter assessor-blinded randomized clinical trial was
      conducted. OBJECTIVES: To investigate the difference in effectiveness of
      manipulative therapy and interferential therapy for patients with acute low back
      pain when used as sole treatments and in combination. SUMMARY OF BACKGROUND DATA:
      Both manipulative therapy and interferential therapy are commonly used treatments
      for low back pain. Evidence for the effectiveness of manipulative therapy is
      available only for the short-term. There is limited evidence for interferential
      therapy, and no study has investigated the effectiveness of manipulative therapy
      combined with interferential therapy. METHODS: Consenting subjects (n = 240)
      recruited following referral by physicians to physiotherapy departments in the
      (government-funded) National Health Service in Northern Ireland were randomly
      assigned to receive a copy of the Back Book and either manipulative therapy (MT;
      n = 80), interferential therapy (IFT; n = 80), or a combination of manipulative
      therapy and interferential therapy (CT; n = 80). The primary outcome was a change
      in functional disability on the Roland Morris Disability Questionnaire. Follow-up
      questionnaires were posted at discharge and at 6 and 12 months. RESULTS: The
      groups were balanced at baseline for low back pain and demographic
      characteristics. At discharge all interventions significantly reduced functional
      disability (Roland Morris scale, MT: -4.53; 95% CI, -5.7 to -3.3 vs. IFT: -3.56;
      95% CI, -4.8 to -2.4 vs. CT: -4.65; 95% CI, -5.8 to -3.5; P = 0.38) and pain
      (McGill questionnaire, MT: -5.12; 95% CI, -7.7 to -2.5 vs. IFT: -5.87; 95% CI, 
      8.5 to -3.3 vs. CT: -6.64; 95% CI, -9.2 to -4.1; P = 0.72) and increased quality
      of life (SF-36 Role-Physical, MT: 28.6; 95% CI, 18.3 to 38.9 vs. IFT: 31.4; 95%
      CI, 21.2 to 41.5 vs. CT: 30; 95% CI, 19.9 to 40; P = 0.93) to the same degree and
      maintained these improvements at 6 and 12 months. No significant differences were
      found between groups for reported LBP recurrence, work absenteeism, medication
      consumption, exercise participation, or healthcare use at 12 months (P > 0.05).
      CONCLUSIONS: For acute low back pain, there was no difference between the effects
      of a combined manipulative therapy and interferential therapy package and either
      manipulative therapy or interferential therapy alone.

PMID- 15480131
TI  - Conditioned medium differentially regulates matrix protein gene expression in
      cells of the intervertebral disc.
AB  - STUDY DESIGN: Matrix protein gene expression was determined for cells of the
      anulus fibrosus (AF) and nucleus pulposus (NP) regions of the intervertebral disc
      when cultured in AF or NP cell-conditioned medium. OBJECTIVES: To investigate
      changes in mRNA levels for type I collagen, type II collagen and aggrecan in
      cells of the AF and NP in response to cell-conditioned medium. SUMMARY OF
      BACKGROUND DATA: Cells of the intervertebral disc have been shown to respond to
      exogenous soluble mediators such as the growth factors TGF-beta and IGF-1. Little
      is known of their biologic response to endogenous factors that may be secreted
      locally or by cells of neighboring regions. METHODS: Porcine cells were cultured
      for 48 hours in alginate gel in the presence or absence of conditioned medium.
      Gene expression for aggrecan and collagens was quantified using real-time reverse
      transcriptase-polymerase chain reaction. RESULTS.: AF cell gene expression was
      generally stimulated by the conditioned medium of either AF or NP cells. In
      contrast, the notochordal cell-containing NP cells showed little change in gene
      expression with either source of conditioned medium. CONCLUSIONS: Cells of the NP
      and AF secrete soluble factors in culture at similarly effective doses to
      stimulate matrix protein gene expression in AF cells of the intervertebral disc.
      Unlike AF cells, however, NP cell gene expression was not stimulated by any
      conditioned medium, suggesting that differences exist in the responsiveness of
      cells of notochordal (NP) and fibrocartilaginous (AF) phenotypes. Understanding
      these differences between cells of the intervertebral disc may reveal unique
      stimulatory factors important to repair and regeneration of the degenerated
      intervertebral disc.

PMID- 15480132
TI  - Cellular, but not matrix, immunolocalization of SPARC in the human intervertebral
      disc: decreasing localization with aging and disc degeneration.
AB  - STUDY DESIGN: Human intervertebral disc anulus tissue was obtained in a
      prospective study of immunolocalization of SPARC (secreted protein, acidic and
      rich in cysteine) (osteonectin). Experimental studies were approved by the
      authors' Human Subjects Institutional Review Board. Discs were obtained from
      surgical specimens and from control donors. OBJECTIVES: To determine whether
      SPARC could be detected in the disc with immunohistochemistry and to determine
      the incidence of SPARC-positive cells. SUMMARY OF THE BACKGROUND DATA: SPARC is a
      glycoprotein that has an important role in modulating interactions between cells
      and matrix. It influences remodeling, collagen fibrillogenesis, metalloproteinase
      expression, and cytokine expression. Little is known about SPARC in the disc, and
      one previous study reported the absence of its immunolocalization in fetal and
      adult disc tissue. METHODS: Eight normal human discs from subjects aged newborn
      to 10 years, and 11 disc specimens from control donors or surgical patients aged
      15to 76 years were examined for immunolocalization of SPARC. Anulus cells were
      also tested for the presence of SPARC in vitro in monolayer or three-dimensional
      agarose culture. RESULTS: In discs of subjects aged newborn to 0.19 years, SPARC
      was present in all cells in the outer anulus, in 76.4% of inner anulus cells, and
      76.0% of nucleus cells. Localization was significantly lower in anulus cells of
      study participants aged 4.7 to 76 years (66.7%, P = 0.04). Anulus cells cultured
      in agarose or monolayer showed positive localization in all cells. CONCLUSIONS:
      Findings show decreased presence of SPARC in disc cells of older subjects with
      disc degeneration and point to the importance of future studies designed to
      elucidate the unrecognized role of SPARC in disc remodeling, aging, and
      degeneration.

PMID- 15480133
TI  - Collagen and proteoglycan abnormalities in the GDF-5-deficient mice and molecular
      changes when treating disk cells with recombinant growth factor.
AB  - STUDY DESIGN: A magnetic resonance image, histologic, biochemical, and gene
      expression study was conducted to characterize the effects of growth and
      development factor-5 (GDF-5) deficiency on the health of the intervertebral disc.
      OBJECTIVE: To determine the effect of GDF-5 deficiency on extracellular matrix
      and gene expression on the intervertebral disc. SUMMARY OF BACKGROUND DATA:
      Developmental and degenerative changes in intervertebral disc are not fully
      understood. Molecular abnormalities and spontaneous mutations that lead to the
      deficiency in a normal protein have been useful in understanding the function of
      certain molecules and the role they play in the structure and health of certain
      tissues. Although the role of GDF-5 in the disc has not been elucidated, this
      factor may have an important role in the disc as a result of the well-documented
      effect of GDF-5 in other chondrogenic tissues. METHODS.: Intervertebral discs of
      20-week-old GDF-5 (-/-) and (+/+) mice were examined radiographically,
      histologically, biochemically, and with gene expression studies. Cells isolated
      from GDF-5-deficient mouse discs were treated with recombinant GDF-5 and gene
      expression was subsequently analyzed. RESULTS: GDF-5 (-/-) mice demonstrated
      significantly lower T2-weighted signal intensity in the central region of their
      lumbar discs, and disc histology revealed loss of the normal lamellar
      architecture of the anulus fibrosus and a shrunken, disorganized nucleus
      pulposus. Biochemical analysis revealed decreased proteoglycan content but no
      appreciable change in total collagen content of the discs. Significant
      downregulation of both aggrecan and type II collagen mRNA, without an appreciable
      change in type I collagen expression, was noted on gene expression studies.
      Recombinant GDF-5 treatment of disc cells from the GDF-5-deficient mice resulted
      in a dose-dependent upregulation of the aggrecan and type II collagen genes.
      CONCLUSION: The intervertebral disc is markedly affected by GDF-5 deficiency.
      This relatively simple (single gene) system with a known molecular defect may be
      useful in studies designed to define the response of the intervertebral disc to
      treatment with growth factor in vivo.

PMID- 15480134
TI  - Distribution and appearance of tumor necrosis factor-alpha in the dorsal root
      ganglion exposed to experimental disc herniation in rats.
AB  - STUDY DESIGN: Distribution and appearance of tumor necrosis factor-alpha (TNF
      alpha) in the dorsal root ganglion (DRG) exposed to experimental disc herniation
      were investigated using an immunohistochemical method in rats. OBJECTIVES: To
      study the distribution and appearance of TNF-alpha in the DRG following
      experimental disc herniation in rats. SUMMARY OF BACKGROUND DATA: Nucleus
      pulposus in the epidural space induces spinal nerve root injury not only by
      mechanical but also chemical mechanisms. Cytokines may play a key role in the
      chemical damage. There is, however, no report on the distribution and appearance
      of TNF-alpha in the DRG exposed to nucleus pulposus. METHODS: Nucleus pulposus
      from the discs was smeared on the glass slides and processed for
      immunohistochemistry by the avidin-biotinylated peroxidase complex technique
      using rabbit antisera to TNF-alpha in rats. A herniation of the nucleus pulposus
      was made by incision of the L4-L5 disc in rats. The L4 and L5 DRGs were resected
      1, 3, 7, 14, and 21 days after surgery. The specimens were processed for
      immunohistochemistry using rabbit antisera to TNF-alpha. The TNF-alpha-positive
      cells were observed and counted using light microscopy. Distribution of the TNF
      alpha products was compared on each day after surgery. RESULTS: A positive
      staining was seen in the cell bodies and in the matrix between the cells in the
      smeared nucleus pulposus. In the L4 DRG sections, the number of positive cells
      was significantly higher in the disc incision group than in the sham group at 1,
      3, 7, and 14 days after surgery (P < 0.05). The positive cells showed a decrease
      in number day by day after surgery. On the contrary, in the L5 DRG, only a few
      positive cells were observed in the disc incision group after surgery. There was
      no statistically significant difference between disc incision and the sham groups
      at each day after surgery for the L5 DRGs. CONCLUSIONS: The immunoreactivity of
      TNF-alpha in the DRG directly exposed to nucleus pulposus increases during 2
      weeks. A collapse of the positive cells was seen in the DRG directly exposed to
      the nucleus pulposus.

PMID- 15480135
TI  - Effect of sagittal plane deformity of the lumbar spine on epidural fibrosis
      formation after laminectomy: an experimental study in the rat.
AB  - STUDY DESIGN: An animal model of postlaminectomy lumbar column sagittal plane
      deformity was designed in rats. OBJECTIVES: To analyze the effect of lumbar
      column deformity (lordosis and kyphosis) on postlaminectomy epidural fibrosis
      formation. SUMMARY OF BACKGROUND DATA: Incidence of peridural fibrosis formation
      after lumbar spinal surgery is considerably high. Instability and sagittal plane
      deformity of the lumbar spine has been implicated (not proven) as the factors for
      the development of epidural fibrosis. The effect of traction (kyphosis) or
      relaxation (lordosis) of the lumbar spine on epidural fibrosis formation is not
      known. METHODS: L4 laminectomies were performed in 30 rats. Three equal groups
      were formed. In the control group (group I), only laminectomy was performed. In
      other groups after laminectomy, lumbar lordosis (group II) and kyphosis (group
      III) was maintained with steel implants. The scar formation was evaluated both
      histologically and histomorphometrically on the 12th postoperative week. RESULTS:
      Kyphosis developed in group I. The mean amount of peridural scar tissue was
      significantly more evident in groups I and III than the lordosis group. The
      extent of adherence to the dura mater and the nerve roots was most apparent in
      group III. CONCLUSIONS: Kyphosis and consequent traction of the lumbar spine is
      one of the causes for increased epidural fibrosis formation after laminectomy. On
      the contrary, establishment of lordosis and relaxation of the lumbar spine
      decreased the scar tissue formation in rats.

PMID- 15480136
TI  - Relationship between axial and bending behaviors of the human thoracolumbar
      vertebra.
AB  - STUDY DESIGN: The authors studied the mechanical behavior of vertebrae through
      the use of finite element analyses. OBJECTIVES: To determine the relation between
      axial and bending rigidity, and to determine the geometric and densitometric
      factors that affect this relation. SUMMARY OF BACKGROUND DATA: Metrics of
      vertebral body mechanical properties in bending have not been established despite
      evidence that anterior bending loads play a significant role in osteoporotic
      vertebral fracture. METHODS: Voxel-based finite element models were generated
      using quantitative computed tomography (QCT) scans of 18 human cadaveric
      vertebral bodies, and both axial and bending rigidities of the vertebra were
      computed. Both rigidity measures and their ratio were correlated with vertebral
      geometric and densitometric factors obtained from the QCT scans. RESULTS: Bending
      rigidity was moderately correlated with axial rigidity (r2 = 0.69) and strongly
      correlated with the product of axial rigidity and vertebral anteroposterior depth
      squared (r2 = 0.88). The ratio of bending to axial rigidity was independent of
      bone mineral density (P = 0.20) but was moderately correlated with the square of
      vertebral depth (r2 = 0.69). CONCLUSIONS: Vertebral anteroposterior depth plays
      an important role in bending rigidity. The scatter in the correlation between
      bending and axial rigidity suggests that some individuals can have vertebrae with
      a normal axial stiffness but an abnormally low bending stiffness. Because whole
      bone stiffness is indicative of bone strength, these results support the concept
      that use of more than one metric of vertebral strength, for example, compression
      and bending strengths, may improve osteoporotic fracture risk prediction.

PMID- 15480137
TI  - Mechanical evaluation of posterior wiring as a supplement to anterior cervical
      plate fixation.
AB  - STUDY DESIGN: An in vitro experimental study was performed to examine 3
      dimensional biomechanical stability of cervical fixations. OBJECTIVES: To
      determine whether posterior interspinous wiring contributes to the rigidity of a
      single-level motion segment that has been plated anteriorly, and to determine the
      effects of this combined fixation on intradiscal pressure and spinal motion at
      the adjacent segments. SUMMARY OF BACKGROUND DATA: Combined anterior and
      posterior column fixation is being increasingly used in a variety of clinical
      situations that do not involve complete disruption of the motion segment. The
      biomechanical validity of combined anterior posterior fixation in the absence of
      overt posterior ligamentous disruption has not been studied. METHODS: Six human
      fresh-frozen cadaveric cervical spines (C3-T1) were used. Three-dimensional
      intersegmental motion and intradiscal pressure were measured while the spine was
      loaded in flexion, extension, lateral bending, and torsion (up to 2.5 Nm).
      Fixation stability at the operative level (C5-C6) and influence of the fixation
      on adjacent segments were evaluated after an anterior plating procedure and
      combined anterior plating and posterior wiring. RESULTS: Comparing the combined
      approach with anterior plating alone, significant reductions in C5-C6 motion was
      noted: 49% in flexion (P <0.05), 48% in extension (P <0.003), and 33% and 39%,
      respectively, in left and right torsion (P <0.05). Reduction in the left and
      right lateral bending was not significant (18% and 12%, respectively). The
      improved fixation had minimal influence on the adjacent segments. CONCLUSIONS:
      Combined anterior posterior fixation further reduces the segmental motion by
      almost 50% in flexion and extension, 33% and 39% in torsion, and does not
      significantly alter intradiscal pressure and spinal motion at adjacent segments.

PMID- 15480138
TI  - Presymptomatic spondylotic cervical cord compression.
AB  - STUDY DESIGN: We conducted a cohort study of clinically asymptomatic spondylotic
      cervical cord compression cases with the primary end point of the development of
      clinical signs of cervical myelopathy. OBJECTIVES: To investigate whether various
      demographic, clinical, radiologic, and electrophysiological parameters could
      predict progression from clinically asymptomatic (preclinical) spondylotic
      cervical cord compression to symptomatic myelopathy. SUMMARY OF BACKGROUND DATA:
      The data available on the prediction of the outcome in surgical and conservative
      treatment of spondylotic cervical myelopathy are controversial. Little is known
      about the clinical natural history of asymptomatic magnetic resonance image
      detected spondylotic cervical cord compression and/or changes of signal
      intensity. METHODS: A group of 66 patients (32 women, 34 men, median age 50
      years) with magnetic resonance signs of spondylotic cervical cord compression but
      without clear clinical signs of myelopathy was followed prospectively for at
      least 2 years (range, 2-8 years; median, 4 years). Various demographic, clinical,
      imaging, and electrophysiological parameters were correlated with clinical
      outcome. RESULTS: Clinical signs of myelopathy during the follow-up period were
      detected in 13 patients (19.7%). The only variables significantly associated with
      the development of clinically symptomatic spondylotic cervical myelopathy (SCM)
      were the presence of symptomatic cervical radiculopathy, electromyographic signs
      of anterior horn lesion, and abnormal somatosensory-evoked potentials. A
      multivariate logistic regression model based on these variables correctly
      classified 90% of cases into 2 subgroups: a group with development of symptomatic
      SCM and that without clinical manifestation of subclinical cervical cord
      compression. CONCLUSIONS: Electrophysiological abnormalities together with
      clinical signs of cervical radiculopathy could predict clinical manifestation of
      preclinical spondylotic cervical cord compression.

PMID- 15480139
TI  - Incidence of subsequent vertebral fracture after kyphoplasty.
AB  - STUDY DESIGN: A retrospective review of charts and radiographs of all consecutive
      patients who underwent kyphoplasty at the authors' center from the initial
      procedure in September 2000 to the end of the collection period in July 2002.
      SUMMARY OF BACKGROUND DATA: The best available natural history data would suggest
      that after experiencing an osteoporotic vertebral compression fracture, patients
      have a 19% incidence of subsequent fracture in the following year when no
      surgical intervention is performed. When kyphoplasty is performed, there are
      conflicting data regarding the incidence of subsequent fracture, ranging anywhere
      from 3 to 29%. These fractures occur at adjacent levels between 30 and 90% of the
      time, with no clear explanation for the wide variation in the results of three
      different studies. There are biomechanical data to suggest that injection of
      cement does increase the stiffness of the treated vertebra and that this
      increases strain on adjacent vertebrae, especially in forward bending. METHODS: A
      database was created containing patient age, gender, height, weight, medication
      history, comorbidities, fracture levels, and pain level before and after surgery.
      Subsequent fractures were confirmed with radiographs and MRI. Statistical
      analysis was performed. RESULTS: Thirty-eight patients (10 men and 28 women) were
      treated for 47 levels initially. L1 and L2 were the most common level of fracture
      managed initially. The gender, smoking and medication history, location of
      fracture, and number of fracture levels of the patients did not correlate with
      the risk of subsequent fracture. Over the follow-up period (average, 8 months),
      10 patients sustained 17 subsequent fractures. Eight patients sustained fractures
      in the first 2 months after the index procedure, all with at least one fracture
      at an adjacent level. Of the 17 subsequent fractures, there were nine at the
      adjacent-above levels, four at adjacent-below levels, and four at remote levels.
      The remote fractures occurred at significantly greater time intervals after the
      index procedure (P < 0.001). CONCLUSION: This study demonstrated a higher rate of
      subsequent fracture after kyphoplasty compared with natural history data for
      untreated fractures. Most of these occurred at an adjacent level within 2 months
      of the index procedure. After this 2-month period, there were only occasional
      subsequent fractures, which occurred at remote levels. This confirms
      biomechanical studies showing that cement augmentation places additional stress
      on adjacent levels. Patients with an increase in back pain after kyphoplasty
      should be evaluated carefully for subsequent adjacent fractures, especially
      during the first 2 months after the index procedure.

PMID- 15480141
TI  - Recovery of neurologic function following nontraumatic spinal cord lesions in
      Israel.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess neurologic
      recovery and the manner in which it is affected by various factors following
      nontraumatic spinal cord lesions (NTSCLs). SUMMARY OF BACKGROUND DATA: NTSCLs
      comprise a considerable portion of spinal cord lesions. However, information
      about neurologic recovery in these lesions is scarce. METHOD: The study sample
      included 1,085 patients with NTSCL treated between 1962 and 2000 at the premier
      referral hospital for rehabilitation in Israel. Demographic and clinical data
      were collected from hospital charts. The degree of neurologic recovery was
      determined by comparing each patient's Frankel grades of neurologic deficit at
      first admission to rehabilitation and at discharge from the same hospitalization.
      The study population was also compared with previously studied 250 patients with
      traumatic spinal cord lesions (TSCLs). RESULTS: Complete or substantial
      neurologic recovery (upgrade to Frankel Grade D or E) occurred during
      rehabilitation in 51% of patients who were Grade A, B, or C on admission, and in
      57% of those who were Grade C. Neurologic recovery in NTSCL during rehabilitation
      was significantly affected by initial Frankel grade and by NTSCL etiology. Age
      had a borderline effect. Gender, lesion level, and the decade of rehabilitation
      did not affect recovery. Recovery rate was usually higher in NTSCLs than in
      TSCLs. CONCLUSIONS: The prognosis for neurologic recovery is affected mainly by
      SCL severity and etiology, and is usually better in NTSCLs than in TSCLs.

PMID- 15480143
TI  - Evaluation of a functional position for lateral radiograph acquisition in
      adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: A retrospective examination of lateral spine radiographs of 50
      patients with adolescent idiopathic scoliosis (AIS) was performed to evaluate the
      sagittal profile of patients in two different standing positions. OBJECTIVES: To
      evaluate segmental and global changes in the sagittal profile of the spine
      associated with two standing radiographic positions and determine if one position
      represents a more functional stance for accurate sagittal balance evaluation.
      SUMMARY OF BACKGROUND DATA: Studies of spinal sagittal balance during relaxed
      standing have indicated that the sagittal vertical axis (SVA), as determine by
      the horizontal displacement of a C7 plumb line from the posterior superior corner
      of the sacrum, is neutral or slightly positive. However, standing with the arms
      forward flexed to allow radiographic visualization of the spine results in a
      negative shift in SVA. METHODS.: Measurements were obtained from standing lateral
      radiographs in patients with AIS in two different standing positions: arms
      forward flexed to 45 degrees with elbows fully extended versus elbows fully
      flexed with fists resting on clavicles. Sagittal plane parameters were analyzed
      using correlation analyses and repeated-measures analyses of variance with
      significance set at 0.005. RESULTS: The study cohort included 25 patients who had
      undergone solely nonoperative treatment (without progression) and 25 patients who
      had undergone operative intervention for their scoliosis. In all patients, SVA
      was more negative (C7 shifted more posterior with respect to the sacrum) when the
      arms were in the forward flexed position compared to the fists on clavicles
      position (-4.2 +/- 2.5 cm vs. -1.3 +/- 2.4 cm, P < 0.001). In operative patients,
      the shoulder forward flexed position was associated with relative posterior
      rotation of the pelvis represented by an average increase of 2.7 +/- 3.8 degrees
      in pelvic tilt (P = 0.002) and an average decrease of 3.2 +/- 4.5 degrees in
      sacral slope (P = 0.002). There was no correlation between the degree of arm
      forward flexion and changes in sagittal measures between the two positions.
      CONCLUSIONS: The fists on clavicles position for lateral radiograph acquisition
      has less negative shift in SVA, and in patients with spinal instrumentation, less
      compensatory posterior rotation of the pelvis. This position is more
      representative of a patient's functional balance while still allowing adequate
      lateral radiographic visualization of the spine.

PMID- 15480144
TI  - The pain disability questionnaire: a new psychometrically sound measure for
      chronic musculoskeletal disorders.
AB  - STUDY DESIGN: The Pain Disability Questionnaire (PDQ) is a psychometric
      evaluation study of a new measure of functional status. OBJECTIVE: To evaluate
      the psychometric properties of the PDQ and compare its validity and
      responsiveness to traditional measures of functional status, such as the
      Oswestry, Million (MVAS), and SF-36 instruments. SUMMARY OF BACKGROUND DATA:
      Measuring clinical outcomes is an essential element of any musculoskeletal
      treatment. The PDQ was developed for this purpose. It yields a total functional
      disability score ranging from 0 to 150. The focus, much like other health
      inventories, is primarily on disability and function. However, unlike most other
      measures, this instrument is designed for the full array of chronic disabling
      musculoskeletal disorders (CDMDs), rather than low back pain alone. Further,
      psychosocial variables, which recent studies have shown to play an integral role
      in the development and maintenance of chronic pain disability, formed an
      important core of the PDQ. METHODS: Four groups were used in this psychometric
      evaluation: an asymptomatic normative population (NP; n = 50), an acute
      musculoskeletal disorder population (AMD; n = 52), a chronic disabled
      musculoskeletal disorder population (CDMD; n = 230), and a heterogeneous pain
      population (HP; n = 114). The NP and AMD groups served as comparison samples for
      the CDMD and HP groups. Analyses of PDQ reliability, validity, and responsiveness
      were conducted. RESULTS: Test-retest reliability coefficients (ranging from 0.94
      to 0.98) and a Cronbach's alpha coefficient of 0.96 for the PDQ were found to be
      of excellent quality. The responsiveness of the PDQ, as measured by Cohen's
      effect size statistic, ranged from 0.85 to 1.07, better than the Oswestry, MVAS,
      and SF-36. A high level of face validity was observed for the PDQ, as the CDMD
      population exhibited significantly higher pretreatment PDQ scores than a group of
      patients suffering from acute injuries. The construct-related validity of the PDQ
      was also found to be of excellent quality, as it correlated well to both the MVAS
      (0.65-0.81) and Oswestry (0.55-0.80). The PDQ consistently demonstrated stronger
      correlation coefficients to a wide variety of physical and psychosocial measures
      of human function, such as the SF-36, Beck Depression Inventory, Hamilton-D,
      State-Trait Anxiety Scale, and Pain Intensity VAS, than either the Oswestry or
      MVAS. A factor analysis of the PDQ revealed two factors: a Functional Status
      Component (FSC) and a Psychosocial Component (PC). Analyses proved each of these
      two components to be valid in assessing their theorized constructs. CONCLUSIONS:
      The present study represents a comprehensive psychometric evaluation of a new
      functional status measure for musculoskeletal conditions in general, and a CDMD
      population in particular. The psychometric properties of the PDQ are excellent,
      demonstrating strong reliability, responsiveness, and validity, relative to many
      other existing measures of functional status. The many weaknesses cited for some
      of the existing measures were taken into account in designing this instrument.
      Consequently, the characteristics commonly noted as weaknesses for these other
      measures (such as a restriction to only the low back pain population, and
      inconsistent responsiveness) can be cited as strengths of the PDQ. Its
      generalizability and utility for assessing orthopedic treatment progress and
      functional outcomes must now be evaluated in broader settings.

PMID- 15480146
TI  - A health production function for persons with back problems: results from the
      Canadian Community Health Survey of 2000.
AB  - STUDY DESIGN: A retrospective, population-based analysis. OBJECTIVES: To analyze
      the relation between health outcomes and resources used by persons with back
      problems in an everyday setting. SUMMARY OF BACKGROUND DATA: The Canadian
      Community Health Survey (2000) contains self-reported variables on change in
      health status, use of health resources, and socioeconomic characteristics of a
      population sample. METHODS: We use a health production function approach, in
      which we explore the association between change in health status and a series of
      utilization variables for persons with a single diagnosis of back pain using a
      regression equation. The independent variables include use of family physicians,
      chiropractors, physiotherapists, and exercise. RESULTS: Change in health status
      was negatively and significantly associated with family practice, chiropractic,
      and physiotherapy visits and positively associated with physical activity. The
      magnitudes of the results were small. CONCLUSIONS: Our results indicate that
      exercise is an important factor in back problems, while persons who seek formal
      care do not improve.

PMID- 15480147
TI  - Patient expectations of treatment for back pain: a systematic review of
      qualitative and quantitative studies.
AB  - STUDY DESIGN: A systematic review of qualitative and quantitative studies.
      OBJECTIVES: To summarize evidence from studies among patients with low back pain
      on their expectations and satisfaction with treatment as part of practice
      guideline development. SUMMARY OF BACKGROUND DATA: Patients are often
      dissatisfied with treatment for acute or chronic back pain. METHODS: We searched
      the literature for studies on patient expectations and satisfaction with
      treatment for low back pain. Treatment aspects related to expectations or
      satisfaction were identified in qualitative studies. Percentages of dissatisfied
      patients were calculated from quantitative studies. RESULTS: Twelve qualitative
      and eight quantitative studies were found. Qualitative studies revealed the
      following aspects that patient expectation from treatment for back pain or with
      which they are dissatisfied. Patients want a clear diagnosis of the cause of
      their pain, information and instructions, pain relief, and a physical
      examination. Next, expectations are that there are more diagnostic tests, other
      therapy or referrals to specialists, and sickness certification. They expect
      confirmation from the healthcare provider that their pain is real. Like other
      patients, they want a confidence-based association that includes understanding,
      listening, respect, and being included in decision-making. The results from
      qualitative studies are confirmed by quantitative studies. CONCLUSIONS: Patients
      have explicit expectations on diagnosis, instructions, and interpersonal
      management. New strategies need to be developed in order to meet patients'
      expectations better. Practice guidelines should pay more attention to the best
      way of discussing the causes and diagnosis with the patient and should involve
      them in the decision-making process.

PMID- 15480148
TI  - Quantifying tissue loads and spine stability while performing commonly prescribed
      low back stabilization exercises.
AB  - STUDY DESIGN: A quantitative biomechanical comparison of seven different lumbar
      spine "stabilization exercises." OBJECTIVES: The purpose of this research was to
      quantify lumbar spine stability resulting from the muscle activation patterns
      measured when performing selected stabilization exercises. SUMMARY OF BACKGROUND
      DATA: Many exercises are termed "stabilization exercises" for the low back;
      however, limited attempts have been made to quantify spine stability and the
      resultant tissue loading. Ranking resultant stability together with spinal load
      is very helpful for guiding clinical decision-making and therapeutic exercise
      design. METHODS: Eight stabilization exercises were quantified in this study.
      Spine kinematics, external forces, and 14 channels of torso EMG were recorded for
      each exercise. These data were input into a modified version of a lumbar spine
      model described by Cholewicki and McGill (1996) to quantify stability and L4-L5
      compression. RESULTS: A rank order of the various exercises was produced based on
      stability, muscle activation levels, and lumbar compression. CONCLUSIONS:
      Quantification of the calibrated muscle activation levels together with low back
      compression and resultant stability assists clinical decisions regarding the most
      appropriate exercise for specific patients and specific objectives.

PMID- 15480149
TI  - Ultraclean air for prevention of postoperative infection after posterior spinal
      fusion with instrumentation: a comparison between surgeries performed with and
      without a vertical exponential filtered air-flow system.
AB  - STUDY DESIGN: This study retrospectively compared infection rates between adult
      patients after posterior spinal instrumentation procedures performed in a
      conventional versus an ultraclean air operating room. OBJECTIVE: To evaluate if
      the use of ultraclean air technology could decrease the infection rate after
      posterior spinal arthrodesis with instrumentation. SUMMARY OF BACKGROUND DATA:
      Postoperative wound infection after posterior arthrodesis remains a feared
      complication in spinal surgery. Although this frequent complication results in a
      significant problem, the employment of ultraclean air technology, as it is
      commonly used for arthroplasty, has not been reported as a possible alternative
      to reduce the infection rate after complex spine surgery. METHODS: One hundred
      seventy-nine patients having posterior spinal fusion with instrumentation were
      divided into 2 groups: group I included 139 patients operated in a conventional
      operating room, and group II included 40 patients operated in a vertical laminar
      flow operating room. Patient selection was performed favoring ultraclean air
      technology for elective cases in which high infection risk was considered. A
      statistical analysis of the infection rate and its associated risk factors
      between both groups was assessed. RESULTS: We observed 18 wound infections in
      group I and 0 in group II. Comparison of infection rates using the chi-squared
      test showed a statistically significant difference (P <0.017). CONCLUSION: The
      use of ultraclean air technology reduced the infection rate after complex spinal
      procedures and appears to be an interesting alternative that still needs to be
      prospectively studied with a randomized protocol.

PMID- 15480150
TI  - Bernardino Ramazzini: the father of occupational medicine.
AB  - Bernardino Ramazzini was born on October 4, 1633, in the small town of Capri
      located in the duchy of Modula, Italy. He is credited with establishing the field
      of occupational medicine during his lifetime. His major contributions came after
      1682, when Duke Francesco II of Modena assigned him to establish a medical
      department at the University of Modena. He was installed in the title of
      professor "Medicinae Theoricae." In 1700, Ramazzini was appointed chair of
      practical medicine in Padua, Republic of Venice, the premier medical faculty in
      Italy. In 1700, he wrote the seminal book on occupational diseases and industrial
      hygiene, De Morbis Artificum Diatriba (Diseases of Workers). Although Ramazzini
      is perhaps most well known for his work on exposure to toxic materials, he wrote
      extensively about diseases of the musculoskeletal system. In particular, he
      warned of the problems of inactivity and poor postures inherent in some jobs.

PMID- 15480152
TI  - Re: Molde Hagen E, Grasdal A, Eriksen HR. Does Early intervention with a light
      mobilization program reduce long-term sick leave for low back pain: a 3-year
      follow-up study. Spine 2003;28:2309-16.

PMID- 15480154
TI  - Re: Throckmorton TW, Hilibrand AS, Mencio GA, et al. The impact of adjacent level
      disc degeneration on health status outcomes following lumbar fusion. Spine
      2003;28:2546-50.

PMID- 15480158
TI  - Hepatitis B and hepatitis C viruses in liver transplantation.
AB  - Liver transplantation (LT) for end-stage liver disease (ESLD) secondary to
      hepatitis viruses has evolved rapidly during the last two decades. ESLD secondary
      to hepatitis C virus (HCV) accounts for approximately 50% of LT in the United
      States and Europe. Despite the decrease in the number of new HCV infections, the
      prevalence of advanced HCV-related liver disease is steadily increasing. In light
      of the near universal recurrence of posttransplantation HCV infection and our
      limited ability to treat recurrent disease, transplantation is in danger of being
      overrun by viral hepatitis, unless effective strategies can be used to treat
      disease, expand the donor pool of available organs, and prevent disease
      recurrence. In the early 1980s, results of LT for chronic hepatitis B virus
      infection were hampered by recurrent infection and subsequent allograft failure.
      However, with the introduction of passive immunoprophylaxis with hepatitis B
      immunoglobulin and treatment with potent nucleoside analogs, there has been a
      resurgence of LT for hepatitis B virus-related ESLD. Despite the wide acceptance
      of LT as a therapy for ESLD, there is little consensus on the appropriate
      immunosuppressive regimens, and prophylactic and therapeutic treatments vary
      widely from one center to another. This review summarizes available data and
      highlights appropriate strategies to improve outcomes.

PMID- 15480159
TI  - Reduced intensity versus truly nonmyeloablative conditioning for stem-cell
      transplant recipients.

PMID- 15480160
TI  - Use of alemtuzumab and tacrolimus monotherapy for cadaveric liver
      transplantation: with particular reference to hepatitis C virus.
AB  - We have proposed that the mechanisms of alloengraftment and variable acquired
      tolerance can be facilitated by minimum posttransplant immunosuppression. It was
      further suggested that the efficacy of minimalistic treatment could be enhanced
      by preoperative recipient conditioning with an antilymphoid antibody preparation.
      A total of 76 adults (38 hepatitis C virus [HCV], 38 HCV) were infused with 30 mg
      alemtuzumab before primary cadaveric liver transplantation and maintained
      afterward on daily monotherapy unless breakthrough rejection mandated additional
      agents. In stable patients, the intervals between tacrolimus doses were
      lengthened ("spaced weaning") after approximately 4 months. Eighty-four
      contemporaneous nonlymphoid-depleted liver recipients (58 HCV, 26 HCV) were
      treated with conventional postoperative immunosuppression. The overall incidence
      of rejection was similar with the two strategies of immunosuppression. With
      follow-ups of 14 to 22 months, patient and primary graft survival in HCV cases
      are 97% and 90%, respectively, with alemtuzumab depletion plus minimal
      immunosuppression versus 71% and 70%, respectively, under conventional
      immunosuppression. In HCV recipients, current patient and graft survival in the
      alemtuzumab-pretreated group are 71% and 70% versus 65% and 54%, respectively,
      under conventional treatment. With both strategies of immunosuppression, the
      adverse effect of preexisting HCV on survival parameters and graft function
      already was significant at the 1-year milestone, but its extent was not evident
      until the second year. With or without HCV, 62% of the 64 surviving lymphoid
      depleted patients are on spaced immunosuppression, and four patients receive no
      immunosuppression. Lymphoid depletion with alemtuzumab and minimalistic
      maintenance immunosuppression is a practical strategy of liver transplantation in
      HCV recipients but not HCV recipients.

PMID- 15480161
TI  - Recurrence risk after organ transplantation in patients with a history of Hodgkin
      disease or non-Hodgkin lymphoma.
AB  - This study defines the incidence and recurrence risk of Hodgkin disease (HD) and
      non-Hodgkin lymphoma (NHL) after organ transplant. Patients from the United
      States with a history of HD or NHL before organ transplantation reported to the
      Israel Penn International Transplant Tumor Registry from 1968 to 2001 were
      analyzed. A total of 91 patients underwent organ transplantation with a lymphoma
      history: HD (38 patients) and NHL (53 patients). Median disease-free interval
      pretransplant was 99 (range 0-459.1) months, and median follow-up posttransplant
      was 25.7 (0.4-131.1) months. Ten patients were excluded from further analysis
      because of lack of follow-up information (n=9) or they never achieved remission
      (n=1). Recurrence incidence was 8 of 81 patients (10%) (HD=3/34 [9%] vs. NHL=5/47
      [11%]). Gender, race, allograft type and source, age at lymphoma diagnosis, and
      immunosuppression did not influence recurrence. Patients with less than a 2-year
      period between diagnosis and transplant seem to be at increased risk of relapse.
      Median disease-free interval before transplant was longer for patients without
      recurrence (115 vs. 30.2 months, P=0.24), but was not statistically significant.
      Median time to recurrence posttransplant was 18.7 (range 1.9-82.2) months (HD=3.7
      vs. NHL 23.6 months, P=0.10). Survival after recurrence was poor (HD [1/3] and
      NHL [1/5], median survival 6.8 [range 0-22.1] months). There is no difference in
      recurrence rates for HD and NHL. The outcome for recurrent lymphoma is poor. The
      low risk of recurrence (10%) indicates that preexisting HD and NHL need not be an
      absolute contraindication to transplantation.

PMID- 15480162
TI  - Effect of brain death on gene expression and tissue activation in human donor
      kidneys.
AB  - BACKGROUND: After kidney transplantation, decreased graft survival is seen in
      grafts from brain dead (BD) donors compared with living donors. This might result
      partly from a progressive nonspecific inflammation in the graft. In this study,
      we focused on the effects of BD on inflammatory response (adhesion molecules,
      leukocyte invasion, gene expression) and stress-related heat shock proteins in
      the human kidney. Research outcomes and clinical donor parameters were then
      linked to outcome data after transplantation. METHODS: Kidney biopsy specimens
      and serum were obtained during organ retrieval from BD and living organ donor
      controls. Immunohistochemistry and semiquantitative reverse transcriptase
      polymerase chain reaction were performed on the biopsy specimens. Clinical and
      laboratory parameters from BD donors were recorded and connected to outcome data
      of the recipients of the kidneys studied. RESULTS: After brain death,
      immunohistochemistry showed an increase of E-selectin (P<0.01) and interstitial
      leukocyte invasion (P<0.05) compared with controls. Also, reverse transcriptase
      polymerase chain reaction showed a threefold increased heme oxygenase-1 (P<0.05)
      and Hsp70 (P<0.01) gene expression after BD. Levels of monocyte chemotactic
      protein-1 and transforming growth factor-beta were twice as high after brain
      death but did not reach significance. Transplantation outcome was influenced by
      several donor variables: positively most notably by donor treatment with
      desmopressin and negatively by high serum urea levels during brain death and by
      high intercellular adhesion molecule and vascular cell adhesion molecule
      expression in the kidney. Heme oxygenase-1 proved to have a protective function,
      but only in kidneys from living donors. CONCLUSIONS: The presence of interstitial
      leukocytes and the early adhesion molecule E-selectin in BD donor kidneys
      indicates an early-phase inflammatory process during organ retrieval. Elevated
      levels of monocyte chemotactic protein-1 and transforming growth factor-beta
      suggest a role for monocytes/macrophages in this phase. We suggest that BD causes
      a stress-related response against which protective heat shock proteins are formed
      in the future graft. This stress response may be too severe to be fully
      counteracted by elevated heat shock proteins. Which systemic and/or local factors
      trigger brain death-related graft injury is currently under investigation.

PMID- 15480163
TI  - Effect of cognate human CD4+ T cell and endothelial cell interactions upon
      chemokine production.
AB  - BACKGROUND: In vitro studies have shown that cognate recognition of antigen
      presented by endothelial cells (EC) causes T cell activation, proliferation, and
      cytokine release and alters the transmigration of T cells. Here we have
      investigated chemokine induction caused by cognate interactions between human
      CD4+ T cells and MHC class II-expressing EC. METHODS: HLA-DR-restricted CD4+ T
      cells were cocultured with HLA-DR-expressing allogeneic Eahy.926, aortic, or
      heart microvascular EC. Chemokine mRNA expression was measured by RTPCR, and
      chemokine protein secreted was measured by a cytokine array system and ELISA.
      Molecules involved in chemokine secretion were identified using blocking
      monoclonal antibodies, and cellular sources of chemokines determined by
      intracellular chemokine staining. Coculture supernatants were also used in
      chemotaxis assays. RESULTS: Nine different chemokine mRNA and proteins were
      expressed because of noncognate interactions between T cells and EC. Cognate
      interactions induced de novo expression of four chemokines and upregulation of
      seven chemokines. Levels of CCL3, CCL8, and CXCL10 secreted into supernatants
      were in the nanomolar range and were chemotactic for T cells and monocytes.
      Blocking antibodies to HLA-DR and LFA-3 abrogated production of CCL3, CCL8, and
      CXCL10. Blocking antibodies to interferon-gamma and tumor necrosis factor-alpha
      inhibited CCL8 and CXCL10 but not CCL3 production. CCL3 and CXCL10 were produced
      by both T cells and EC. CONCLUSIONS: Cognate interactions between alloreactive
      CD4+ T cells and MHC class II-expressing EC results in a specific pattern of
      chemokine production. These chemokines could play important roles in recruitment
      of leukocytes into vascularised allografts.

PMID- 15480164
TI  - Human leukocyte antigen antibodies and human complement activation: role of IgG
      subclass, specificity, and cytotoxic potential.
AB  - BACKGROUND: Human leukocyte antigen (HLA) antibodies are defined as complement
      (C) fixing and clinically relevant based upon the complement-dependent
      cytotoxicity (CDC) test. However, the sub-lytic activation of individual C
      components is of critical biologic significance. The requirements of HLA
      antibodies to activate human C are not known. METHODS: IgG, IgM, IgG subclasses,
      and human C3b deposition upon T cells were evaluated by flow cytometry with sera
      from HLA-sensitized patients and human monoclonal HLA antibodies. RESULTS:
      Comparative studies showed that there was poor correlation between the amount of
      IgG on target cells and their ability to produce CDC. Human C3b deposition was
      influenced more by the particular serum/cell combination under study than by the
      amount of IgG, with some combinations showing high IgG and low C3b and others
      showing low IgG and high C3b. IgG1 was the predominant IgG subclass in all
      patients. The other subclasses were low or undetectable and did not correlate
      with C3b deposition. Human monoclonal HLA antibodies, mostly IgG1, did not
      activate human C efficiently despite high IgG binding. However, combinations of
      two monoclonal antibodies to different epitopes of the same antigen did produce
      significant C3b deposition. CONCLUSIONS: Contrary to common assumptions, CDC, IgG
      binding, and IgG subclass are poor predictors of human C activation by HLA
      antibodies. The mix of specificities in a given serum and the antigens of a
      particular target cell appear to determine the efficiency of C activation.
      Measuring both antibody and C3b deposition (or other C component) may improve the
      assessment of donor-recipient compatibility.

PMID- 15480165
TI  - Surveillance of acute rejection in baboon renal transplantation by elevation of
      interferon-gamma inducible protein-10 and monokine induced by interferon-gamma in
      urine.
AB  - BACKGROUND: CXCR3 binding chemokines play a key role in recruitment of
      inflammatory cells into an organ transplant. This study addresses the question of
      whether urinary excretion of these chemokines correlates with acute rejection in
      a baboon kidney transplantation model. METHODS: Seven outbred baboons underwent
      renal allotransplantation from major histocompatibility complex (MHC)-mismatched
      donors. The treatment of baboons consisted of anti-CD4 monoclonal antibody (mAb),
      anti-CD8 mAb, rapamycin, and mycophenolate mofetil (MMF). Urinary levels of
      interferon-gamma inducible protein-10 (IP-10) and monokine induced by interferon
      gamma (Mig) were determined by ELISA. Renal biopsies were examined by
      immunohistochemical staining for CXCR3 and Mig. RESULTS: Urinary levels of IP-10
      and Mig increased significantly in all of the five baboons at the time of acute
      rejection of renal transplant. The IP-10 and Mig levels did not rise in two
      nonrejecting baboons. In two baboons, urinary levels of IP-10 and Mig rose before
      the elevation of the serum creatinine. In renal biopsies, expression of Mig was
      detected in glomeruli, tubules, and infiltrating cells, and the expression was
      significantly elevated in biopsies with acute rejection (P<0.01). CXCR3 was
      constitutively expressed in tubular cells in biopsies derived from both normal
      grafts and grafts with acute rejection. Whereas the infiltrating cells were
      increased in the biopsies with acute rejection, the expression of CXCR3 was also
      significantly higher (P<0.01) in these infiltrating cells compared with those in
      the normal controls. CONCLUSIONS: This study shows an important correlation
      between urinary excretion of IP-10 and Mig and acute rejection in baboon kidney
      transplantation.

PMID- 15480166
TI  - Evaluation of eight preservation solutions for endothelial in situ preservation.
AB  - BACKGROUND: Non-heart-beating donors (NHBDs) have the potential to reduce the
      increasing numbers of patients on kidney and liver graft waiting lists. One
      problem observed with kidneys obtained from NHBDs is the endothelial injury seen
      on protocol core biopsies after implantation. We postulate that this is caused by
      a combination of warm ischemia, cold ischemia, and hypertonic citrate during in
      situ preservation (ISP) rather than hypothermic machine preservation. Our aim was
      to optimize ISP methods to preserve endothelial structure and function. METHODS:
      An animal model of ISP was used to compare the ability of eight different
      preservation solutions to protect mammalian vascular tissue exposed to a
      combination of warm and cold ischemia. Smooth muscle contractile function and
      endothelial dependent relaxation (nitric oxide production) were determined using
      an organ bath method. RESULTS: Bretchneider's HTK solution preserved the ability
      of endothelial tissue to relax vascular tissue in response to acetylcholine (91%
      relaxation vs. 17% saline control; ANOVA, P<0.001); in stark contrast, Marshall's
      solution performed no better than saline (15% relaxation vs. 17% saline control,
      P=NS). UW solution (80%) and a derivative lacking the starch colloid (70%) were
      comparable with HTK. Belzer-MPS (55%), Celsior (57%), and Perfadex (44%) showed a
      roughly equivalent level of endothelial preservation. Electron microscopy
      confirmed an anatomical loss of structure correlating with loss of function.
      CONCLUSIONS: ISP requires a large volume of fluid to be pumped at high flow
      rates. In this model, HTK retained a powerful ability to preserve endothelial
      structure and function during warm ischemia.

PMID- 15480167
TI  - A comparison of nonmyeloablative and reduced-intensity conditioning for
      allogeneic stem-cell transplantation.
AB  - BACKGROUND: Nonmyeloablative (NM) conditioning and reduced-intensity conditioning
      (RIC) are increasingly used for allogeneic hematopoietic stem-cell
      transplantation. Such regimens have not been compared. METHODS: The primary
      endpoint was graft-versus-host disease (GVHD). Secondary endpoints included
      transfusions, engraftment, and transplant-related mortality (TRM). NM
      conditioning (n=24) consisted of fludarabine and 2-Gy total-body irradiation
      followed by immunosuppression with cyclosporine A (CsA) combined with
      mycophenolate mofetil (MMF). The RIC (n=34) protocol consisted of fludarabine
      combined with busulfan or cyclophosphamide, antithymocyte globulin, and
      posttransplant immunosuppression CsA plus methotrexate. Diagnoses included
      hematologic malignancies and solid tumors. Donors were 34 human leukocyte antigen
      identical siblings and 24 unrelated donors. Chimerism was analyzed by polymerase
      chain reaction of minisatellites. RESULTS: Graft failure occurred in 6 of 24 in
      the NM group and in 1 of 34 in the RIC group, which was a significant difference
      (odds ratio [OR], 22.6; P=0.02). The NM group also had less leukopenia and
      required fewer erythrocyte and platelet transfusions than the RIC group. The time
      to and proportion of CD3, CD19, and CD45 donor chimerism were similar in both
      groups. The cumulative incidence of grades II to IV acute GVHD was higher in the
      NM group (59% vs. 12%; OR, 26.9; P<0.001), but we found no difference in the
      cumulative incidence of chronic GVHD (41% vs. 61%). TRM was 42% in the NM group
      and 20% in the RIC patients (relative hazard, 11.6; P=0.03). CONCLUSIONS: NM
      conditioning with posttransplant immunosuppression using CsA and MMF resulted in
      less leukopenia and fewer transfusions, but resulted in more cases of graft
      failure, acute GVHD, and TRM than in RIC patients.

PMID- 15480168
TI  - Outcome of renal transplantation in South Asian recipients is similar to that in
      non-Asians.
AB  - BACKGROUND: The United Kingdom has a large South Asian population, in which there
      is a high rate of renal disease and which forms a significant percentage of the
      renal transplant waiting list. Information about short- and long-term transplant
      outcomes in this ethnic group is limited, although it has been suggested that
      graft survival is poorer in this population compared with non-Asians. METHODS:
      The authors examined the outcome and determinants of medium-term (5-year)
      survival in 245 renal transplants, 53 of which were performed in South Asian
      patients between 1995 and 2002. RESULTS: Three-year survival with a functioning
      graft was 89% for the non-Asians and 85% for the South Asians. At 5 years, this
      deviated to 83% and 70%, respectively, for the two groups, but this did not reach
      statistical significance. Acute rejection rates were similar in the two groups.
      South Asian ethnicity was not a significant predictor of medium-term graft loss
      in the authors' study. CONCLUSIONS: In this cohort of patients, South Asian
      ethnic background did not confer a survival disadvantage after renal
      transplantation.

PMID- 15480170
TI  - Increased rejection in living unrelated versus living related kidney transplants
      does not affect short-term function and survival.
AB  - BACKGROUND: At our institution, increased kidney donation from unrelated donors
      accounts for a steady rise in live donor kidney transplantation rates. We
      compared outcomes of living related (LRT) versus living unrelated kidney
      transplants (LURT) and analyzed the effect of early rejection upon graft
      survival. METHODS: A retrospective analysis on 428 adult living donor kidney
      transplants was performed. Graft function and survival were compared between LRT
      and LURT and risk factors for 1-year rejection were defined by multivariate
      analysis. RESULTS: Between 1/1/97 and 12/31/01, 308 LRT and 120 LURT were
      performed at the University of California San Francisco. Donor age and number of
      mismatches were significantly higher in the LURT group. Patient and graft
      survival were similar in both groups. After a median follow-up of 26 months,
      graft survival was 94.8% (LRT) versus 93.3% (LURT). Five-year serum creatinine
      levels were comparable in both populations. One-year rejection was higher in the
      LURT group (30% vs. 18.5%; P<0.01). Rejection was influenced by the number of
      human leukocyte antigen mismatches. Other independent risk factors for early
      rejection were poor initial graft function, donor age greater than 55 years, and
      recipient body mass index greater than 30. Patients with poor initial graft
      function and early rejection had a statistically greater incidence of
      subtherapeutic tacrolimus trough levels on postoperative day 7. CONCLUSIONS:
      Despite a higher incidence of early rejection, LURT show similar function and
      survival compared with LRT. In high-risk patients receiving living unrelated
      renal transplants, consideration should be given to intensify initial
      immunosuppression to prevent early rejection episodes.

PMID- 15480169
TI  - Pulmonary angiography for the diagnosis of thromboembolic events in the non-human
      primate.
AB  - BACKGROUND: Evaluating possible thromboembolic events in the non-human primate
      has traditionally required euthanasia, significantly limiting the ability to
      conduct longitudinal studies. We hypothesized that pulmonary angiography could
      offer a safe, reproducible, and non-lethal means to assess for pulmonary embolus
      in the non-human primate. METHODS: Eleven rhesus primates were studied using
      standard pulmonary angiography techniques. Five animals studied had previously
      received humanized anti-CD154 antibodies (associated with thromboembolism risk)
      in the context of skin transplantation 2 years before the angiography study. Four
      primates were studied after receiving mouse anti-human CD154 antibody following
      allogeneic islet or skin transplantation. RESULTS: Angiography was successful in
      all primates. We observed no complications, and all animals promptly recovered
      from the procedure. Angiographic findings consistent with thromboembolism were
      demonstrated in the three primates actively receiving anti-CD154 antibody and in
      one primate that last received anti-CD154 nearly 2 years before the study. The
      study was normal in both the streptozotocin-induced diabetic control animals.
      Histopathology of the lungs confirmed thrombus in two of the four primates, but
      no thromboembolus was identified in the other two. The first had limited
      pathologic evaluation without fine slices, and in the second (treated 2 years
      before with a humanized anti-CD154), ascariasis was found in the area identified
      as abnormal by the angiogram. CONCLUSIONS: Minimally invasive pulmonary
      angiography is a safe, reproducible, and inexpensive method to assess possible
      thromboembolic events in the non-human primate. This method may allow for the
      longitudinal assessment of non-human primates given novel agents that may promote
      thromboembolism.

PMID- 15480171
TI  - Association of cytomegalovirus disease and acute rejection with graft loss in
      kidney transplantation.
AB  - BACKGROUND: Cytomegalovirus (CMV) and acute rejection (AR) alone have been
      associated with an increased risk of graft loss in kidney transplantation.
      However, little is known about their association with graft loss when both affect
      the transplant recipient. METHODS: By using the dynamic time-varying covariate
      approach to the Cox-proportional hazards model, we retrospectively analyzed the
      strength of association of AR and CMV disease on graft loss in a single-center
      kidney and simultaneous pancreas-kidney transplant population. RESULTS: Between
      January 1990 and December 2000, 2,740 kidney and simultaneous pancreas-kidney
      transplants were performed at the authors' center. The overall 5-year incidence
      of biopsy-proven AR and CMV disease was 45.8% (n=1,254) and 15.3% (n=420),
      respectively. The risk ratio (RR) for graft loss was increased by the presence of
      AR (RR=3.7; P<0.0001), CMV disease (RR=1.9; P=0.0007), AR following CMV disease
      (RR=6.6; P<0.0001), and CMV disease following AR (RR=3.3; P<0.0001). In patients
      with AR and CMV disease the average time until AR occurred was longer (441 days)
      when AR followed CMV disease in comparison with when AR preceded CMV disease (47
      days). After adjusting for time-dependent risk of AR for kidney graft loss, the
      order of AR and CMV disease had no association with graft loss (RR=1.2;
      P=0.5055). CONCLUSIONS: These results demonstrate the strength of AR and CMV
      disease as prognosticators of impeding kidney graft loss in transplant
      recipients. Although AR usually precedes CMV disease, the order of AR and CMV
      disease has no impact on kidney graft loss in kidney and simultaneous pancreas
      kidney transplant recipients.

PMID- 15480172
TI  - Patient-specific prompts in the cholesterol management of renal transplant
      outpatients: results and analysis of underperformance.
AB  - BACKGROUND: Renal transplant recipients have an increased risk of cardiovascular
      disease compared with age- and gender-matched controls. It is recommended that
      "high-risk" patients are treated with hydroxymethylglutaryl CoA reductase
      inhibitors to reduce cholesterol levels. METHOD: We evaluated the effect of a
      computer-based decision support algorithm in delivering patient-specific prompts
      to manage cholesterol in renal transplant outpatients. Data were analyzed
      retrospectively for a 2-year period with attention to changes in cholesterol
      levels, prescribing patterns of statins, and causes of underperformance. RESULTS:
      At baseline, 36.7% of patients achieved a total serum cholesterol level less than
      5.0 mmol/L, compared with 67.2% at 2 years, with mean values of 5.6+/-0.1 mmol/L
      and 4.8+/-0.1 mmol/L (P<0.0001). At baseline, 24% of the patients were receiving
      statin therapy, increasing to 61% at 2 years. There were no significant changes
      in creatinine phosphokinase, trough cyclosporine levels, or total cyclosporine
      dose. Alkaline phosphatase levels increased (166.1+/-3.6-184.6+/-6.1 mmol/L,
      P=0.009), but remained within the normal clinical range; creatinine clearance
      increased (58.6+/-1.0-61.0+/-1.2 mL/min, P=0.05). For patients followed
      concurrently in two units without the algorithm, serum cholesterol measurements
      decreased from 5.57 mmol/L and 5.34 mmol/L to 5.31 mmol/L and 5.27 mmol/L,
      respectively (P=0.05), both higher than that achieved contemporaneously at St.
      James's. Underperformance depended less on medical noncompliance than with
      systematic features of the methodology and patient preference/collaboration with
      treatment. CONCLUSIONS: The introduction of the algorithm coincided with a
      significant reduction in cholesterol levels, an increase in the number of
      patients receiving appropriate therapy, and no serious adverse effects. Our
      results illustrate the positive effect of computer-generated prompts and decision
      support software.

PMID- 15480173
TI  - Preoperative and perioperative predictors of the need for renal replacement
      therapy after orthotopic liver transplantation.
AB  - BACKGROUND: Acute renal failure developing after orthotopic liver transplantation
      (OLTx) requiring renal replacement heralds a poor prognosis. Our center has
      previously reported a 1-year survival of only 41.8%. We undertook this study to
      determine whether we could identify preoperative and perioperative factors that
      would predict which patients are at risk. METHODS: OLTxs performed between
      January 1, 1996, and December 31, 2001, were included in our retrospective
      database review. Combined kidney-liver transplants or patients with preoperative
      renal replacement therapy (RRT) were excluded. A total of 724 OLTxs were studied,
      which were divided into group I: no RRT, n=637; group II: hemodialysis only post
      OLTx, n=17; and group III: continuous RRT post-OLTx, n=70. Univariate and
      stepwise logistic multivariate analyses were performed. RESULTS: Preoperative
      serum creatinine greater than 1.9 mg/dL (odds ratio [OR] 3.57), preoperative
      blood urea nitrogen greater than 27 mg/dL (OR 2.68), intensive care unit stay
      more than 3 days (OR 10.23), and Model for End-Stage Liver Disease score greater
      than 21 (OR 2.5) were significant. A clinical prediction model was constructed:
      probability of requiring dialysis posttransplant=(-2.4586+1.2726 [creatinine
      >1.9] + 0.9858 [blood urea nitrogen >27] + 0.4574 [Model for End-Stage Liver
      Disease score >21] + 1.1625 [intensive care unit days >3]). A clinical prediction
      rule for patients with a score greater than 0.12 was applied to OLTx recipients
      who underwent transplantation in 2002. A total of 15 of 20 patients who received
      RRT and 111 of 121 who did not were correctly classified with the model.
      CONCLUSIONS: This model allowed us to identify patients at high risk for
      developing the need for RRT postoperatively. Strategies for these patients to
      prevent or ameliorate acute renal failure and reduce the need for RRT
      postoperatively are needed.

PMID- 15480174
TI  - Avascular osteonecrosis after allogeneic hematopoietic stem-cell transplantation:
      diagnosis and gender matter.
AB  - BACKGROUND: Avascular osteonecrosis (AVN) is a serious complication of allogeneic
      stem-cell transplantation (SCT). Acute and chronic graft-versus-host disease and
      its treatment with steroids are identified as main risk factors. In a single
      center, prospective cohort study of patients undergoing allogeneic SCT for
      chronic myeloid leukemia (CML), acute myeloid leukemia, myelodysplastic syndrome,
      and acute lymphatic leukemia, we determined the incidence of hip AVN
      necessitating total arthroplasty (severe adverse event) and performed risk factor
      analysis. METHODS: A total of 255 patients were followed for an observation
      period of at least 4 years. Thirteen potential risk factors including age,
      recipient and donor gender, underlying disease and disease stage, conditioning
      therapy, human leukocyte antigen match, acute or chronic graft-versus-host
      disease, and immunosuppressive medication were tested in univariate and
      multifactorial nominal logistic and Cox proportional hazard analyses. RESULTS:
      Severe adverse events occurred in eight patients (4-year cumulative incidence
      rate 6.1%). Univariate and multifactorial analysis revealed a diagnosis other
      than CML and steroid intake as main risk factors (chi model 31.6, P=0.0005; chi
      diagnosis 11, P=0.001; chi steroid 6.8, P=0.009). The demonstrably strong
      influence of diagnosis was steroid independent (steroid intake in CML comparable
      to non-CML). We repeated the analysis in 103 patients without CML (70 with acute
      myeloid leukemia, 13 with myelodysplastic syndrome, and 20 with acute lymphatic
      leukemia), excluding 152 patients with CML. Univariate and multifactorial
      analyses revealed female gender (of both recipient and donor) as risk factors for
      AVN in addition to steroids. Relative AVN risk for female compared with male
      donor transplantation was 8.7 (P=0.01); relative AVN risk for female compared
      with male recipient transplantation was 4.3 (P=0.047). CONCLUSIONS: Diagnosis and
      gender are steroid-independent risk factors for severe hip AVN after allogeneic
      SCT.

PMID- 15480175
TI  - Baseline immunosuppression is associated with histological findings in early
      protocol biopsies.
AB  - BACKGROUND: Protocol biopsies performed in stable renal allografts show different
      degrees of acute and chronic lesions that have been related with graft outcome.
      However, the utility of protocol biopsies to manage baseline immunosuppression
      has not been well characterized. METHODS: We performed a case-control study to
      compare histological lesions observed in protocol biopsies in 49 patients treated
      with tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisone to 49 patients
      treated with cyclosporine Neoral (CsA), MMF, and prednisone. Histological lesions
      were graded according to 1997 Banff criteria. The analysis was done according to
      an intention-to-treat basis. RESULTS: Patients treated with TAC displayed in the
      protocol biopsy a lower acute score (0.61+/-1.01 vs. 1.26+/-1.45; P=0.0115) and a
      similar chronic score (1.57+/-1.97 vs. 1.51+/-1.59; P=NS). Transplant
      glomerulopathy was also lower in TAC treated patients (0.02+/-0.14 vs. 0.20+/
      0.41; P=0.0037). Univariate and multivariate logistic regression analysis showed
      that the presence of acute inflammation was associated with tacrolimus treatment
      (relative risk [RR]: 0.30, 95% confidence interval [CI]: 0.11-0.84; P=0.0211) and
      the time of biopsy (RR per month: 0.56, 95% CI: 0.32-0.97; P=0.0394). The
      presence of chronic lesions was only associated with serum creatinine at the time
      of biopsy (RR: 1.01, 95% CI: 1.00-1.02; P=0.0439). CONCLUSIONS: The incidence of
      inflammatory lesions and transplant glomerulopathy is lower in patients treated
      with TAC than in patients treated with CsA. These data suggest that baseline
      immunosuppression could influence the severity of histological lesions in stable
      grafts.

PMID- 15480176
TI  - BK virus-associated nephropathy in renal allograft recipients: rescue therapy by
      sirolimus-based immunosuppression.
AB  - BACKGROUND: BK virus nephritis (BKN) in recipients of renal allografts has
      reemerged during the past 5 years. Despite increased incidence, therapeutic
      options remain limited and progression of the disease often leads to allograft
      failure. METHODS: From May 2002 to July 2002, we performed protocol biopsies in
      25 recipients of kidney allografts with progressive allograft dysfunction; three
      patients demonstrated unexpected histopathologic features of BKN. We tested the
      hypothesis that replacement of their lymphocytotoxic and nephrotoxic
      immunosuppression (combination of mycophenolate and tacrolimus) with sirolimus-
      and prednisone-based therapy can lead to disappearance of the virus without
      increasing the risk of acute rejection. RESULTS: During the median follow-up of
      18 months after sirolimus and prednisone therapy, decoy cells disappeared first,
      followed by progressive decrease in the median plasma BK virus-DNA load, and
      undetectable levels at the last follow-up. Patients remained free of acute
      rejection, and follow-up median estimated creatinine clearance increased to 67
      mL/min (range 62-75 mL/min) from 52 mL/min (range 51-54 mL/min) at the time of
      diagnosis. CONCLUSIONS: Further studies are needed, but at present these
      preliminary results offer a new direction for therapeutic intervention in
      recipients of renal allografts with BKN.

PMID- 15480177
TI  - Ipsilateral placement of simultaneous pancreas and kidney allografts.
AB  - The current standard technique for simultaneous kidney pancreas transplantation
      usually involves transplanting the pancreas to the right and the kidney to the
      left iliac system. Here we describe a previously unreported technique where both
      organs are transplanted to the right iliac system through a single midline
      incision. Forty-nine patients underwent simultaneous ipsilateral pancreas and
      kidney transplantation. All pancreas grafts were drained enterically. Overall
      patient, pancreas, and kidney survival were 96% (47/49), 92% (45/49), and 94%
      (46/49) respectively. The 45 patients with functioning grafts are insulin free
      and off of dialysis. Mean serum creatinine at 1, 3, 6, and 12 months was 1.7+/
      1.3, 1.2+/-0.3, 1.3+/-0.3, and 1.3+/-0.4 mg/dL, respectively. The placement of
      the pancreas and kidney transplants on the same side is safe and does not
      compromise patient or graft survival. This approach preserves the left iliac
      system for future retransplantation if necessary.

PMID- 15480178
TI  - Impact of HLA-A,B,C allele mismatches on outcome after unrelated blood stem cell
      transplantation in whites.
AB  - At our institution the selection of unrelated donors for hematopoietic stem cell
      transplantation (HSCT) relies on low resolution human leukocyte antigen (HLA)-A,B
      and high resolution HLA-DRB1,DQB1 DNA-based typing. To answer the question of
      whether routine high resolution HLA-A,B,C typing might improve HSCT outcome, 171
      white "HLA-identical" donor/recipient pairs, as stated by our pretransplant
      tissue typing routine, were retyped for HLA-A,B,C using sequence based typing
      (SBT). The numbers of HLA-A,B,C allele mismatches detected by SBT were correlated
      to established clinical endpoints of HSCT outcome. We found 33.9% of the study
      transplants to be fully HLA-A,B,C matched, whereas 66.1 % exhibited one through
      four donor/recipient HLA-A,B,C allele mismatches. However, statistical analysis
      could not demonstrate an impact of the number of HLA-A,B,C allele mismatches on
      overall survival and other analyzed endpoints. Thus, our series of white
      donor/recipient pairs does not suggest the routine use of HLA-A,B,C SBT to
      improve HSCT outcome substantially.

PMID- 15480179
TI  - Increased infection-related mortality in KIR-ligand-mismatched unrelated
      allogeneic hematopoietic stem-cell transplantation.
AB  - Recently, attention has been focused on the role of killer cell immunoglobulin
      like receptor (KIR)-ligand incompatibility between donor and recipient in
      allogeneic hematopoietic stem-cell transplantation (ASCT). Although KIR-ligand
      mismatch is clearly associated with improved survival in haploidentical ASCT for
      acute myeloid leukemia, its role in unrelated human leukocyte antigen-mismatched
      ASCT is more controversial. Here we present a retrospective analysis of KIR
      ligand-matched (n=167) and mismatched (n=23) unrelated ASCTs for hematologic
      malignancies performed at a single center. We observed that KIR-ligand mismatch
      was associated with increased transplantation-related mortality (P=0.02), leading
      to decreased overall survival (P=0.01). The increased transplantation-related
      mortality was a consequence of a higher rate of infections (P=0.01), whereas
      incidence of graft-versus-host disease and leukemic relapse did not differ
      significantly between the two groups. These results suggest that the presence of
      donor-derived, alloreactive natural killer cells may interfere with immunity to
      infection in the early posttransplantation period.

PMID- 15480180
TI  - Interleukin-8, neutropenia, and graft failure in human stem cell transplantation.
AB  - We studied the role of interleukin (IL)-8 during engraftment after hematopoietic
      stem cell transplantation. In 40 consecutive patients undergoing either
      allogeneic marrow (n=32) or autologous peripheral blood stem cell transplantation
      (n=8), IL-8 plasma levels were serially determined. Median IL-8 concentrations
      peaked during the neutropenic phase and, subsequently, subsided to pretransplant
      levels in patients achieving engraftment. In all patients, we observed an inverse
      correlation of IL-8 with leukocytes (P<0.0001) and a direct correlation of IL-8
      with the extent of neutropenia (P<0.0001). Four patients who developed graft
      failure showed sustained median IL-8 concentrations of >300 pg/mL together with
      persistent neutropenia. This marked elevation of IL-8 was statistically
      significant as early as day 11 after transplantation, at a time when no other
      evidence alluded to imminent graft failure. Our data suggest that IL-8 may play
      an important role during engraftment after hematopoietic stem cell
      transplantation.

PMID- 15480182
TI  - Hepatocyte growth factor serum levels after partial hepatectomy.

PMID- 15480183
TI  - A case report of a spontaneous subcapsular hematoma leading to rupture of the
      liver in a patient following a renal transplant.

PMID- 15480189
TI  - Navigating the neonatal brain through the base of the skull: an effective
      sonographic teaching tool.
AB  - The neonatal head is routinely evaluated with ultrasound within hours after
      birth. The most common images obtained are coronal and sagittal views using the
      anterior fontanel as a window. Routine scanning protocols should include
      representative images of intracranial structures that are reproducible from one
      examination to another. The shape of the base of the skull can provide landmarks
      that can ensure reproducibility of examinations using a minimum of 11 images. The
      use of these landmarks makes it possible to have a consistent technique to
      localize anatomic structures and pathology in both planes.

PMID- 15480190
TI  - Various sonographic appearances of the hemorrhagic corpus luteum cyst.
AB  - Although hemorrhagic corpus luteum cysts are frequently seen during sonography of
      the female pelvis, their diagnosis is often challenging as a result of variations
      in size, thickness of the cyst wall, and internal echo pattern depending on the
      formation and lysis of the clot. There are cases in which hemoperitoneum is the
      most obvious finding. The differential diagnosis is extensive and includes
      ectopic pregnancy, adnexal torsion, neoplasm, and pelvic inflammatory disease.
      This review describes and illustrates the diverse appearances of the hemorrhagic
      corpus luteum, as well as other etiologies of adnexal pathology that can mimic
      the appearance of a hemorrhagic corpus luteum sonographically.

PMID- 15480191
TI  - Sonographic diagnosis of primary malignant tumors of the fallopian tube.
AB  - The purpose of this study is to illustrate the sonographic features of primary
      malignant tumors of the fallopian tube and to heighten awareness of their
      existence. This is a retrospective review of the imaging and clinical files of 7
      patients with a primary malignant tumor of the fallopian tube found in the
      medical records of 4500 patients with primary gynecologic malignancies seen
      during the last 6 years at the authors' institution. All patients had
      transvaginal sonography before surgery. Images were reviewed to determine common
      features of this rarely encountered pathology. Transvaginal sonography showed
      normal ovaries in 5 patients in association with a discrete solid adnexal mass in
      4. The fallopian tube origin of the mass was shown directly in 2 of these 4
      patients and was inferred in the other 2 on the basis of a mass in the expected
      location of the fallopian tube. In the 3 patients without a discrete adnexal
      mass, there were more extensive changes, including large, solid adnexal masses of
      unknown origin (n = 2) and gross peritoneal carcinomatosis (n = 1). Fallopian
      tube malignancies should be considered when unexplained solid masses
      corresponding with the expected location of the fallopian tubes are seen in
      association with normal ovaries. Disease dissemination may show carcinomatosis or
      more extensive pelvic disease.

PMID- 15480214
TI  - Sonographic findings of uterine polypoid adenomyomas.
AB  - Based on a retrospective analysis of 32 patients with polypoid adenomyomas of the
      uterus, the authors have identified 3 sonographic patterns: solid (pattern 1, 8
      cases), solid with cystic areas (pattern 2, 22 cases), and predominantly cystic
      (pattern 3, 2 cases). Sonographic features include a heterogeneously isoechoic,
      polypoid, or pedunculated endometrial mass, with an ill-defined margin,
      hemorrhagic foci, posterior shadowing, and associated adenomyosis in the
      myometrium. Knowledge of these sonographic appearances may facilitate the
      diagnosis of polypoid adenomyoma and help differentiate it from other polypoid
      uterine tumors.

PMID- 15480215
TI  - Ultrasound of tropical and infectious diseases that affect the scrotum.
AB  - Ultrasonography of the scrotum permits assessment of testicular and
      extratesticular masses with high sensitivity. It can differentiate a variety of
      conditions involving the scrotum, testicles, and epididymis with similar clinical
      manifestations, including infectious and tropical diseases. The authors performed
      conventional and color Doppler ultrasonographic examinations in 76 patients who
      presented with scrotal pain, swelling, and/or tenderness. Their diagnoses
      included sexually transmitted disease (eg, gonorrhea, syphilis, chlamydial
      infection), tuberculosis, mumps, and various tropical diseases (eg, filariasis,
      leishmaniasis, schistosomiasis, paracoccidioidomycosis). The most common imaging
      findings were enlarged hypoechoic testes, hypervascularity, small hydroceles, and
      cutaneous edema. This report reviews these and other possible presentations of
      tropical and infectious diseases affecting the scrotum, emphasizing ultrasound
      findings that facilitate diagnosis.

PMID- 15480216
TI  - The role of radiology in the era of compact ultrasound systems: SRU Conference,
      October 14 and 15, 2003.

PMID- 15480255
TI  - [Biological Resource Centers: the institutional point of view].

PMID- 15480257
TI  - [Adenocarcinomas of the stomach and distal esophagus. Incidence and phenotypic
      characteristics of EBV-associated cases in the Lyons area, France].
AB  - AIMS: Our study aimed to evaluate the incidence of EBV-associated adenocarcinomas
      of the stomach and distal esophagus in Lyons area and to assess their phenotypic
      characteristics. METHODS: 85 cases of gastric adenocarcinomas and 40 cases of
      esophageal adenocarcinomas were screened for EBV by in situ hybridization (EBER-1
      and -2) and immunohistochemistry (LMP1 and EBNA-1); all cases positive for EBER
      by in situ hybridization were studied by PCR for demonstration of EBV DNA. The
      clinical, histological and immunophenotypic features of EBV-associated
      adenocarcinomas were assessed. RESULTS: 5 cases of EBV-associated
      adenocarcinomas, all gastric, were identified in our series (5.8%); one was
      diagnosed in a migrant from Algeria, a region of high endemia of EBV infection. 3
      cases were located in the proximal stomach, 1 in the distal; 1 was diffuse. 4
      cases were of the intestinal histological type. Proliferation index and
      microvessel density were high in all 5 cases. The expression of tumor markers was
      markedly heterogeneous from one case to another. CONCLUSIONS: Our study shows
      that EBV infection is restricted to gastric adenocarcinomas. Its incidence is
      evaluated to 5.8% in our series: this shows that Lyons area must be considered as
      a low risk area. In the absence of specific histological or phenotypic features,
      the screening of EBV+gastric adenocarcinomas is possible only with special
      techniques.

PMID- 15480258
TI  - [Amyloidosis of the seminal vesicles: a local condition with no systemic impact].
AB  - AIM: Localised seminal vesicle amyloidosis is relatively infrequent and we
      present 9 additional cases. MATERIAL: and methods: Those 9 cases were
      retrospectively retrieved from 803 radical prostatectomies performed between 1995
      and 2000 for prostatic adenocarcinoma. In each case, the type of amyloidosis was
      characterised by immunohistochemistry. Information regarding a possible
      concurrent disease or prior hormone therapy has been obtained. RESULTS: The
      prevalence of amyloidosis of seminal vesicles is lower in our study (1.1%) than
      in unselected autopsy cases. The prevalence of amyloidosis in patients exposed to
      prior hormone therapy (LHRH agonist and anti-androgen) was 2% while it reached
      only 0.9% in those who received no hormone therapy (p>0.3). No patient had
      systemic amyloidosis and all cases were of non A-A type. Lactoferrin, a
      glycoprotein produced by normal seminal vesicles, was detected in more than a
      half of them (5/9). CONCLUSION: No association was found between the occurrence
      of seminal vesicle amyloidosis and occurrence of a prostatic adenocarcinoma,
      corcomitant systemic disease or exposure to prior hormone therapy. Seminal
      vesicle amyloidosis is a localised condition without systemic involvement and
      amyloid deposition is composed mostly of lactoferrin.

PMID- 15480259
TI  - [Hematodermic CD4/CD56 neoplasm].
AB  - Hematodermic CD4/CD56 neoplasm is a recently described entity. This name has been
      initially proposed by the French Study Group on Cutaneous Lymphomas which
      established the primary anatomoclinical and pathogenic and cytogenic bases of the
      disease in 1999. This descriptive and provisional name allowed conceptualizing
      the entity by its main clinical and phenotypical characteristics. The first case
      in the literature goes back to 1994. Since that time, several other cases have
      been published. The expression of CD56 led most of the authors to propose an NK
      cell lineage origin. In the last WHO classification of lymphomas, the entity was
      indexed under the name of "blastic NK-cell lymphoma". However, the authors
      underlined that there were currently no clues to the etiology of blastic NK-cell
      lymphoma and that the precise lineage of this disease was still unresolved. At
      the clinical level the main characteristics of the disease are the skin tropism
      and the occurrence of a leukemic phase at any time during the course of the
      disease. The median age is 59 but pediatric cases do exist. At the morphological
      level skin biopsy shows a monomorphous cell proliferation simulating a
      pleomorphic T cell cutaneous lymphoma. The diagnosis is based on phenotypic
      criteria which require frozen tissue. Currently, the main characteristics are the
      expression of CD4 and CD56 antigens while the main defined lineage specific
      markers are negative (B-cell, T-cell, NK-cell and myeloid-cell lineages). The
      origin of the tumor cells still remains uncertain but the plasmacytoid dendritic
      cell is presently a very serious candidate. The tumor cells share a great
      phenotypical homology and particularly the expression of the CD123 antigen.
      Functional homologies have also been demonstrated with tumor cells in vitro.
      Outcome of CD4/CD56 hematodermic neoplasms is very bad. The median time of
      survival is 14 months irrespective of the treatment given. Conventional
      chemotherapies used for the treatment of aggressive lymphomas or acute myeloid
      leukemias are quickly inefficient.

PMID- 15480260
TI  - [Fatal Dieulafoy's type ulcer in a case of gastric AL-amyloidosis].
AB  - Dieulafoy's ulcer is a particular form of gastric ulcer confined to a persistent
      caliber artery and may lead to severe hemorrhage. We report a case of fatal
      gastric bleeding in a woman with benign biclonal gammapathy. Autopsy found a
      typical Dieulafoy's ulcer centered by a persistent caliber artery which wall was
      thickened by AL-amyloid deposits. Amyloidosis involved the gastric wall, but also
      middle caliber arteries of the liver, the lung, the pancreas, the kidney and the
      myocardium. AL-amyloidosis is a rare and late complication of monoclonal
      gammapathy and may be asymptomatic. Pathogenesis of Dieulafoy's ulcer remains
      unclear. In our case, local ischemia may have facilitated gastric ulceration, and
      amyloid deposits may have contributed to arterial rupture.

PMID- 15480261
TI  - [Infiltrating lobular carcinoma of the breast with histiocytoid features: three
      cases].
AB  - Histiocytoid carcinoma of the breast, a cellular variant of invasive breast
      cancer, is mainly found among infiltrating lobular carcinomas (ILC). It can be
      easily confused with benign conditions or other mammary tumors also composed of
      cells with a pink granular to foamy cytoplasm and an eccentric nucleus. We report
      3 cases of histiocytoid ILC. Our aim is to discuss recent immunocytochemical data
      that could suggest a special type of apocrine differentiation of tumor cells,
      including a diffuse immunoreactivity for GCDFP-15 (Gross Cystic Disease Fluid
      Protein 15) and a predominant expression of androgen receptor, and to describe
      the features useful for the differential diagnosis.

PMID- 15480262
TI  - [Thyroid metastases of an adrenocortical carcinoma 41 years after the diagnosis
      of the primary tumor].
AB  - Thyroid metastasis are rare and represent less than 4% of malignant thyroid
      tumors in clinical series. They can develop many years after diagnosis of the
      primary tumor. We report a case of thyroid metastasis of adrenocortical
      carcinoma, 41 years after the diagnosis of the primary tumor. Such a long latent
      interval is exceptional. To our knowledge, this is the first case published.
      Based on current literature, we offer a brief review on thyroid metastasis and
      differential diagnosis of thyroid gland clear cell neoplasm.

PMID- 15480263
TI  - [Systemic metastasis at the time of diagnosis of a glioblastoma].
AB  - Metastatic gliomas are quite rare. We report a case of glioblastoma multiforme
      with bone marrow metastasis at the time of diagnosis, revealed by a bicytopenia.
      An autopsy was performed and several visceral metastases were discovered in the
      lung, the mediastinal lymph nodes and in the spleen.

PMID- 15480265
TI  - [Nasal and auricular inverted papillomas].
AB  - We report a rare case of an inverted papilloma with an unusual clinical course:
      development in the middle ear, multiples recurrences, and invasion of the
      temporal bone.

PMID- 15480264
TI  - [A large para-renal PEComa].
AB  - We report the case of a 45-year-old man with a voluminous para-renal mass. The
      tumor was composed of epithelioid or spindle-shaped eosinophilic and clear cells
      with some atypia and an elevated mitotic count. The immunohistochemical study was
      positive for anti-HMB45 antibodies and anti-actin-antibodies and negative for
      epithelial markers and PS100 antibodies. The diagnosis of epithelioid AML
      (PEComa) was established. Two years later, recurrence was observed with a
      voluminous mass in the left upper quadrant of the abdomen, with high cellular
      density and the same immunohistochemical features. This tumor belongs to the
      PEComa and is not easy to diagnose clinically and morphologically. The
      immunohistochemical phenotype is characteristic. AML are usually benign but some
      epithelioid AMLS outcome can be unfavorable with metastatic dissemination.
      Criteria of malignancy are not clearly defined in the literature. This case shows
      that the mitotic count and the tumor size are probably important.

PMID- 15480267
TI  - [Image in pathology. Congenital hepatic fibrosis].

PMID- 15480266
TI  - [Breast carcinoma with predominant neuroendocrine differentiation].
AB  - Neuroendocrine differentiation can be identified in a subset of human breast
      carcinomas, either as scattered cells or as a predominant neuroendocrine
      component. We report a case of an invasive breast carcinoma largely composed of
      neuroendocrine cells. Eight years after a left mammary lumpectomy for a pT2N1MO
      SBR III invasive ductal carcinoma, a 67-years-old woman presented with a
      metastastic neuroendocrine sternal mass. To establish a relationship between
      mammary carcinoma and bone metastasis, histological slides of both the breast
      tumor and axillary lymph nodes were reviewed, and an immunohistochemical study
      was performed. They showed that: a) the mammary carcinoma was composed of a
      majority of small and large neuroendocrine cells synaptophysin +, NCAM+,
      chromogranin - (80%), associated with 2 other differentiated non endocrine
      components, one of metaplastic squamous carcinoma (10%) and the other of ductal
      carcinoma (10%); b) 4 axillary lymph nodes were involved by the ductal component
      which contained few NCAM + but synaptophysin - cells; c) Estrogen and
      progesterone receptors and HER2 were negative in the breast tumor and the
      metastatic nodes. We discuss the histogenesis of composite mammary carcinomas
      with neuroendocrine differentiation, the outcome of each component and the
      prognostic relevance of such a diagnosis.

PMID- 15480268
TI  - [A skin nodule which developed for 30 years!].

PMID- 15480269
TI  - [An unusual cause of recurrent anal fistula].

PMID- 15480270
TI  - [Lung mass revealed by multiple subcutaneous nodules].

PMID- 15480271
TI  - [A rare inguinal tumor].

PMID- 15480272
TI  - [Para-epididymal deposit of Tamm-Horsfall protein].

PMID- 15480275
TI  - [First trimester ultrasound should be a tailored examination].

PMID- 15480276
TI  - [Female genital mutilation: generalities, complications and management during
      obstetrical period].
AB  - OBJECTIVES: Evaluation of female genital mutilation complications and their
      clinical management. MATERIAL AND METHODS: Review of the literature. RESULTS:
      Female genital mutilation is still performed in some regions of Africa. Although
      female genital mutilation are often considered as a religious act, tradition and
      social habits seems to be the best explanation. Infibulation is the most severe
      form, in which the clitoris, the labia minora and part of labia majora are
      removed. Stitching of the raw surfaces created covers the urethra and the vaginal
      entrance. There only remains a small opening at the base of the vulva. Health
      consequences directly depend on the severity of the initial mutilation. They are
      more severe in infibulated women. Pregnancy, childbirth and the obstetrical
      period are particuliary dangerous for the mother and the child. Female genital
      mutilation contributes to childhood and maternal mortality and morbidity.
      Decreasing the impact depends on the obstetrical team's competence. Defibulation
      is absolutely necessary for the delivery of infibulated women. This simple
      surgical act can be performed under local anesthesia. CONCLUSION: With increasing
      immigration, obstetrical teams in developed countries can be confronted with such
      situations. They should be aware of proper clinical management practices for
      these women.

PMID- 15480277
TI  - [Negative impact of cigarette smoking on male fertility: from spermatozoa to the
      offspring].
AB  - Cigarette smoking has negative effects on male fertility. Recent studies showed
      an active transfer of several components of cigarettes through the blood-testis
      barrier. The presence of these components in the seminal plasma may induce a
      degradation of sperm parameters and nuclear quality of spermatozoa, and
      compromise the chances of pregnancy. Moreover, smoking may have a negative impact
      on the smokers'offspring: poor quality embryos, development of childhood cancers.
      Oxidative stress-induced DNA damage seems to be one of the major causes of sperm
      quality alteration. Several methods are now available to analyze the degree of
      DNA fragmentation. In order to optimize the success rate of assisted reproduction
      technologies, the deleterious effects of smoking on male fertility and the
      necessity of cessation have to be explained in detail to these patients.

PMID- 15480278
TI  - [Medical treatment of ectopic pregnancy: a randomized clinical trial comparing
      metotrexate-mifepristone and methotrexate-placebo].
AB  - BACKGROUND: Medical treatment of ectopic pregnancy is widespread. To increase the
      efficacy of methotrexate, combination with mifepristone has been proposed.
      METHODS: We performed a large prospective multicentre double-blind sequential
      randomized trial in order to compare the efficacy of methotrexate and
      mifepristone (600 mg given orally) versus methotrexate and placebo. RESULTS: Two
      hundred twelve ectopic pregnancies were randomized. There was no significant
      difference in the initial characteristics between the 2 groups. There was no
      significant difference in the success rate of medical treatment between the
      methotrexate-mifepristone (n=113) and the methotrexate-placebo group (n=99):
      79.6% (90/113) vs 74.2% (72/97) respectively, RR [95% CI]: 1.07 [0.92-1.25],
      p=0.41. However, there was a quantitative interaction between progesterone level
      and effect of treatment: when progesterone level was 10 ng/l, the efficacy of the
      combination of mifepristone and methotrexate was significantly higher than the
      combination of methotrexate and placebo, with a 83.3% success rate (15/18) vs
      38.5% (5/13) respectively. CONCLUSION: Our study failed to demonstrate any
      benefit of the addition of mifepristone to methotrexate. By contrast, the
      quantitative interaction between treatment effect and base line serum
      progesterone suggested that this combination could be reserved to ectopic
      pregnancies associated with high serum progesterone concentrations.

PMID- 15480279
TI  - [Medical treatment of early spontaneous miscarriages: a prospective study of
      outpatient management using misoprostol].
AB  - OBJECTIVES: Medical treatment using misoprostol has been recommended as an
      alternative to surgical evacuation for spontaneous miscarriages in the first
      trimester, in order to avoid anesthesia, a surgical operation and
      hospitalization. Our aim was to assess the efficacy and the safety of vaginal
      misoprostol in out-patient management of early miscarriages. MATERIAL AND
      METHODS: We conducted a prospective cohort study including patients with a
      spontaneous miscarriage of less than 14 weeks gestation. Exclusion criteria were
      hemorrhagic miscarriages, gestational sac larger than 40 mm and/or cranio-caudal
      length of the embryo of more than 30 mm. Our protocol used 4 intravaginal tablets
      (800 microg) of misoprostol on Day 1, out-patient follow-up, clinical and
      ultrasound reassessment on Day 2. If the intra-uterine antero-posterior diameter
      on ultrasound examination was greater than 15 mm (or the gestational sac
      persisted), a second dose of misoprostol was administered or surgical evacuation
      was performed (failure of medical treatment). RESULTS: One hundred two patients
      were included, of whom 30 had an inevitable or threatened miscarriage and 72 had
      a missed abortion. The success rate defined by complete expulsion of the products
      of conception without resorting to surgical evacuation and without short-term
      complications, was 78.4% (80 patients). Two patients were lost to follow-up at 48
      hours. Complete expulsion occurred within 2 days in 94% of cases. There were 13
      emergency consultations, including 8 for expulsion pain and five surgical
      evacuations (3 for hemorrhagic expulsion, 2 for hemorrhagic retention). All
      together, there were 15 surgical evacuations for retention of the products of
      conception after 1 or 2 doses of misoprostol. There was one case of endometritis
      (1%). Thirty-four patients were hospitalized, 22 for surgical evacuation and 12
      for expulsion pain. CONCLUSION: It is possible to use misoprostol as a single
      vaginal dose (800 microg) as out-patient treatment, since it gives satisfactory
      efficacy (80%) and is sufficiently safe (5% needing emergency surgery). However,
      out-patient management should only be performed after explaining the treatment
      and its risks clearly to the patient.

PMID- 15480280
TI  - [Acceptability of the etonogestrel-containing contraceptive implant (Implanon)].
AB  - OBJECTIVES: To estimate the exact satisfaction of women toward Implanon, the sole
      contraceptive implant available in France. To clarify the indications of this
      type of contraception. MATERIAL AND METHOD: Among a population of 182 women with
      Implanon" inserted in a same family planning service between May 22, 2001 and
      February 14, 2003, 108 women agreed to answer a questionnaire of satisfaction.
      Implants were inserted in one third of cases after childbirth, in another third
      after abortion. The average duration of use of the implant was of 16 months (2 in
      24 months). Twenty-nine removals among the 108 insertions (27%) were recorded.
      RESULTS: Possibility of a long-term and easy -to-use contraception was the most
      common reason for choosing Implanon (74% of the women). Eighty-one percent of the
      women were globally satisfied with Implanon but one out of two women had side
      effects. Only 62% of the women were ready to use it again. Adverse events were
      first, menstrual disturbance in 83% of the women, mainly amenorrhea (26%) and
      bleeding irregularity (40%). Bleeding irregularity was one of the main motives
      for discontinuing the implant in 41% of cases. Except weight gain present for 37%
      of patients, the other side-effects, even though they were frequent, were less
      often the reason for removal. Headache, acne, breast pain, mood and decreased
      libido were the main reasons for removal. CONCLUSION: Implanon has certainly a
      place among current contraceptive methods. Because of the frequency raised by
      adverse events and by their lower tolerance in Europe, this place has to remain
      limited to the incapacity of classic methods. Preinsertion counseling announcing
      Implanon's benefit and risk effects is necessary to minimize the early
      discontinuation rates.

PMID- 15480281
TI  - [Management of delivery in patients with Marfan's syndrome presenting aortic
      dilatation].
AB  - OBJECTIVE: We report the anesthesic and obstetrical management of two pregnant
      patients with Marfan's syndrome. An important dilatation of the root of aorta was
      established at the beginning of the pregnancy. Based on a review of the
      literature and our experience, we searched for clues to identify the ideal term
      and the best mode of delivery, and which type of anesthesia may be the more
      appropriate in patients with aortic dilatation. RESULTS: No consensus can be
      found in the literature as far as anesthesia and obstetric management of these
      patients is concerned. Pregnancy must be continued as long as possible to ensure
      adequate fetal growth but fetal extraction should not be delayed if the diameter
      of the aorta enlarges too much. A diameter of 40 mm is probably the higher limit
      to accept for vaginal delivery. Beyond, cautious cesarean section would be
      advisable. In the absence of dural ectasia or a technical problem, neuraxial
      anesthesia is a good option. CONCLUSION: According to the severity of the aortic
      dilatation and its evolution, specific management, based on good cooperation
      between obstetricians and anesthesiologists, is the key of a successful and safe
      childbirth.

PMID- 15480282
TI  - [Maternal mortality estimation in France, according to a new method].
AB  - OBJECTIVE: Ten years after implementation of maternal mortality monitoring in
      France, we established a new estimate of the current maternal mortality ratio
      (MMR) and revisited maternal death data collection. MATERIAL AND METHODS:
      Linkages were set up between female deaths and childbirths and between female
      deaths and causes of death. Information provided by confidential inquiries into
      maternal deaths carried out by the National Committee for maternal mortality
      study was added. The World Health Organization (WHO) definitions were used for
      maternal death and maternal mortality ratio. The study concerned deaths occurring
      in 1999. Results were compared with data from 1989. RESULTS: The official data
      showed 20% fewer maternal deaths than our inquiry. Estimated from our data, the
      MMR was 9 per 100000 live births in 1999. Direct obstetric causes were more often
      recorded than indirect causes. Hemorrhage was the leading obstetric cause of
      maternal death (21%). In comparison with the 1989-90 data, the underestimation of
      maternal deaths and maternal mortality ratios are improving (from 18 to 9 per
      100000). CONCLUSION: These results, obtained while the mean maternal age at
      childbirth increased regularly, are interpreted as a sign of improvement in care.
      But the persistence of post partum hemorrhages as the leading cause of maternal
      death and the high rate of avoidable deaths, disclose important targets for
      further progress.

PMID- 15480283
TI  - [Postpartum ovarian vein thrombophlebitis: report of 5 cases and review of the
      literature].
AB  - OBJECTIVE: Postpartum ovarian vein thrombophlebitis (POVT) is an uncommon life
      threatening situation. It should be systematically evoked in case of persistent
      fever during the postpartum. We describe here the imaging techniques to assert
      the diagnosis and the different therapeutic options. METHODS AND MATERIAL: We
      report five cases from 1997 to 2002. Only one patient was surgically treated.
      RESULTS: No death was observed. In all cases, fever and pain rapidly disappeared.
      CONCLUSION: Search for postpartum ovarian vein thrombophlebitis should be
      undertaken in patients with persistent fever. Treatment is more often medical.

PMID- 15480284
TI  - [Bowel obstruction revealing post-traumatic diaphragmatic hernia in a pregnant
      woman].
AB  - We describe a case of late post-traumatic diaphragmatic hernia revealed during
      pregnancy by bowel obstruction. The diagnosis was made during exploratory
      laparotomy at 29 weeks. After surgical repair of the hernia the pregnancy went to
      term uneventfully. A healthy baby was delivered at 39 weeks by elective cesarean
      section.

PMID- 15480285
TI  - [Antenatal discovery of megacystis-microcolon-intestinal hypoperistalsis syndrome
      (MMIHS) at 12 weeks gestation].
AB  - Megacystis on antenatal scan in female fetuses is rare and has diagnostic
      implications. We report a case of megacystis-microcolon-intestinal
      hypoperistalsis syndrome (MMIHS) in a female infant. The antenatal scan revealed
      abnormalities, but the diagnosis was not established until after delivery. MMIH
      is a rare autosomal recessive condition which is usually lethal in the first year
      of life. Prenatal diagnosis is hampered by the lack of specific diagnostic
      ultrasound findings and the absence of an identified genetic locus.

PMID- 15480286
TI  - Labor pain and labor analgesia.

PMID- 15480287
TI  - [About: "Evaluation of cesarean rate" by P. Rozenberg (J Gynecol Obstet Biol
      Reprod 2004; 33: 279-89)].

PMID- 15480288
TI  - [The use of politics for changing social relationships between the sexes].

PMID- 15480289
TI  - [Gender differences in premature mortality and avoidable deaths].
AB  - OBJECTIVE: This paper aims to describe and to analyse disparities between men and
      women for "premature" mortality rates (deaths before 65 year-old). The study is
      particularly focused on "avoidable" causes of death. These types of deaths are
      greatly related to risk behaviours such as alcohol abuse, tobacco abuse or
      dangerous driving. Taking account of these indicators ("premature" and
      "avoidable" mortality) enables to study health status discrepancies by gender and
      to characterize specific public health issues in France including high rates of
      "premature" mortality and risk behaviours. METHODS: The analysis is based on
      exhaustive mortality data from 1980 to 1999 supplied by the Centre for
      epidemiology of medical causes of death (CepiDc-INSERM). Specific causes of death
      closely related to risk behaviours are classified as "avoidable": lung and upper
      airways cancers, cirrhosis, alcoholic psychosis, traffic accidents, aids and
      suicide. The contribution of these categories in the global male overmortality
      was assessed according to different demographic and geographic characteristics.
      RESULTS: Within "premature" mortality, males experience greater burden of
      "avoidable" mortality (sex-ratio: 4 versus 2). The gender differences are mainly
      due to injuries and suicides in the younger age groups and to tobacco and alcohol
      related cancers (lung and upper airways) in the 45-64 years age group. The recent
      decline in "premature" mortality sex-ratio is explained by an increase of these
      two cancers for females. Among european countries, the French male overmortality
      is especially marked and mainly attributable to "avoidable" causes of death.
      CONCLUSION: "Avoidable" and "premature" mortality provide useful tools for the
      follow-up of health status in France particularly because of high risk behaviours
      and prevention inadequacy. Reducing gender discrepancies will depend mainly on
      public health policies in terms of primary prevention.

PMID- 15480291
TI  - [Gender gap in life expectancy: the reasons for a reduction of female advantage].
AB  - BACKGROUND: After a large increase during the 19th and the 20th century, for two
      decades the gap in life expectancy between sexes has been reducing in most
      industrialised countries. In France, where it was specially large, it stopped
      increasing in the early 1980s and decreased in the most recent years. The paper
      investigates reasons for these recent trends in France and in the industrialised
      countries. METHODS: Two types of data are used for analysis. Death probabilities
      from life tables are used for calculating male excess mortality by age and
      estimating the role of various age groups in life expectancy differences by sex.
      Sex- and cause-specific mortality rates from INED database for France and from
      WHO database for other countries are used to assess the part played by various
      causes of death in the gender gap and its evolution. RESULTS: In France, the
      stabilisation of the gap is mainly related to the decrease in cardiovascular
      mortality for men who benefit from the same progress but later than women. In the
      most recent years, the reduction of the gap is due to the trend reversal of male
      cancer mortality which is now decreasing, specially because of the reduction of
      lung cancer mortality. In European countries, taken as examples (England & Wales,
      Sweden, Switzerland, Italy) cardiovascular mortality is also the main responsible
      for the decreasing differences. Conversely, in Japan, the gap is still increasing
      specially for mortality from cancer and respiratory diseases. CONCLUSIONS: The
      recent gap narrowing between male and female life expectancy in France is not a
      specific case. It does not mean that female health situation is worsening but it
      is related to an acceleration of progress for males. This reduction will most
      probably go on in the next years, except if females would enjoy dramatic
      progression in old age mortality.

PMID- 15480292
TI  - Macroscopic epidemiology and the lessons of history.

PMID- 15480293
TI  - [Differences between males and females in traffic accident risk in France].
AB  - BACKGROUND: In France 7,720 people were killed in traffic accidents in 2001, 75%
      of which were men; the number of injured people is estimated at 153,945, of which
      65% were men. The objective of the study is to describe differences between males
      and females regarding accidents, and to explain the main reasons for these
      differences. METHODS: Analysis is conducted from both national police data (2001)
      and data from the Rhone medical road accident trauma Register (1996-2001).
      RESULTS: The male/female incidence rate is 3.1 for mortality (95% CI: 3.0-3.3)
      and 1.7 for morbidity (95% CI: 1.7-1.8). Two-wheel motorised vehicle accidents
      are very specific to males, which explains part of this overrepresentation. The
      fatality rate and the severe injuries rate among survivors are higher for males.
      This is true for every main user group (car users, motorised two-wheelers,
      cyclists, pedestrians) after adjusting for accident circumstances and age of
      casualties. Males are more severely injured for all body regions and have more
      often severe after-effects. CONCLUSIONS: This paper shows the mechanisms leading
      to this unfavourable outcome for men. They correspond to differences in the
      number of trips, in the choice of road transport types, and moreover to
      differences in risk-taking behaviours. Underlying these behaviours, deep-rooted,
      strong and rather invariant differences between genders are to be found in the
      values associated with risk-taking on the road.

PMID- 15480294
TI  - [Risk of driving: male aggressiveness, violence, and delinquency].

PMID- 15480295
TI  - [The influence of technical products on sexual activity and gender relations:
      oral contraceptive, condom, oral treatments of sexual disorders].
AB  - Over the past fifty years, sexuality has been marked by an increasing interest in
      sexual and reproductive health. This progression can be seen in changes in
      legislation, in social norms, in sexual practices and in gender relations. It is
      also characterised by the introduction and use of various technical products,
      which have a direct impact on both sexual activity and its consequences:
      contraception, methods of sexually transmissible infections prevention and
      treatment for male impotence. Irrespective of their usefulness or their technical
      effectiveness, these different products are endowed with a symbolic identity that
      reflects dominant representations of sexuality and the sexual roles of men and
      women. An analysis of the way in which these products are used illustrates how
      they have contributed to the development of scenarios of sexual relations, by
      distributing specific roles to men and to women. Three models of sexuality
      associated with each product have been analysed: liberated sexuality, protected
      sexuality, and functional sexuality.

PMID- 15480296
TI  - [Male and female sexuality in the 20th century: transformations? Revolutions?
      Freedom?].

PMID- 15480297
TI  - Levothyroxine addendum.

PMID- 15480298
TI  - Duloxetine (Cymbalta): a new SNRI for depression.

PMID- 15480299
TI  - Influenza vaccine 2004-2005.

PMID- 15480300
TI  - Direct binding of visual arrestin to a rhodopsin carboxyl terminal synthetic
      phosphopeptide.
AB  - PURPOSE: The phosphorylated carboxyl terminus of rhodopsin is required for the
      stable binding of visual arrestin to the full length rhodopsin molecule.
      Phosphorylation of the carboxyl terminus has been shown to induce conformational
      changes in arrestin, which promote its binding to the cytoplasmic loops of
      rhodopsin. However, it has not been determined whether phosphorylation is also
      responsible for the direct binding of the rhodopsin carboxyl terminus to
      arrestin. To further investigate the role of rhodopsin phosphorylation on
      arrestin binding, surface plasmon resonance was used to measure the interaction
      between a synthetic phosphopeptide corresponding to the carboxyl terminus of
      rhodopsin and visual arrestin in real time. METHODS: Synthetic peptides were
      generated that correspond to the phosphorylated and nonphosphorylated carboxyl
      terminus of bovine rhodopsin. These peptides were immobilized on a biosensor chip
      and their interaction with purified visual arrestin was monitored by surface
      plasmon resonance on a BIAcore 2000 or 3000. RESULTS: A synthetic peptide
      phosphorylated on residues corresponding to Ser-338, Thr-340, Thr-342 and Ser-343
      of bovine rhodopsin was sufficient for direct binding to visual arrestin. In
      contrast, a second phosphopeptide phosphorylated on Thr-340 and Thr-342 and a
      nonphosphorylated synthetic peptide were not able to bind arrestin. A peptide
      fully substituted at all serine and threonine residues with glutamic acid was
      unable to substitute for phosphorylation. CONCLUSIONS: Surface plasmon resonance
      is a sensitive method for detecting small differences in affinity. We were
      successful in using this technique to detect differences in the affinity of
      phosphorylated and nonphosphorylated rhodopsin peptides for visual arrestin. The
      data suggest that these are low-affinity interactions and indicate that
      phosphorylation is responsible for the direct binding of the rhodopsin carboxyl
      terminus to visual arrestin. Four phosphorylated residues are sufficient for this
      interaction. Because the affinity of the synthetic phosphopeptide for arrestin is
      substantially lower than the full length rhodopsin molecule, the cytoplasmic
      loops and rhodopsin carboxyl terminus appear to interact in a cooperative manner
      to stably bind arrestin.

PMID- 15480301
TI  - The 5' flanking sequence of the human retGC1 gene acquires a photoreceptor cell
      restricted activity pattern over the course of retinal development.
AB  - PURPOSE: Specific mutations of the retinal guanylyl cyclase-1 (retGC1) gene have
      been linked to Leber congenital amaurosis type 1 (LCA1) and cone-rod dystrophies
      in humans, diseases that are amenable to treatments using molecular based
      therapies. As a step towards developing a therapeutic transgene for LCA1, we
      analyzed the cell specific and developmental activity profiles of fragments of
      the human retGC1 5' flanking region in vivo. METHODS: We generated self
      inactivating lentiviral vector constructs carrying three different fragments of
      the human retGC1 promoter fused to a nuclear localized beta-galactosidase
      reporter gene (nlacZ). The transgenes were packaged into lentiviral vectors,
      which were then used to transduce retinal progenitor cells of the developing
      chick. We monitored the expression of nlacZ in the retina over the course of
      development and in the retina, brain and pineal gland just prior to hatching.
      RESULTS: A 1.8 kb fragment of the retGC1 5' flanking region upstream of Exon 2
      was capable of targeting nlacZ expression to photoreceptor cells in vivo and its
      activity was augmented by the presence of intron 1. We also demonstrated that the
      cell specific activity of this fragment arises, at least in part, by silencing
      expression in non-photoreceptor cells during the final stages of retinal
      development. CONCLUSIONS: We have identified a human retGC1 promoter fragment
      that exhibits photoreceptor cell specific activity in vivo. Our results suggest
      that an element located in the proximal promoter may play a role in silencing
      expression of this gene in non-photoreceptor cells, thereby by shaping the
      restricted expression pattern of GC1 in the retina.

PMID- 15480302
TI  - Effects of dexamethasone on posterior capsule opacification-like changes in a rat
      lens explant model.
AB  - PURPOSE: Many patients whose sight is initially restored by cataract surgery
      eventually suffer secondary loss of vision because of posterior capsule
      opacification (PCO; after-cataract), a condition in which lens epithelial cells
      left behind at surgery become aberrant and migrate into the light path. The aim
      of this study was to determine whether dexamethasone (DEX), an anti-inflammatory
      agent widely used before and after cataract surgery, influences the behavior of
      lens cells under conditions relevant to PCO development. METHODS: An established
      rat PCO model was used in which explanted epithelial cells attached to the lens
      capsule are exposed sequentially to TGFbeta2 and FGF-2. Cultures with or without
      DEX (100 nM), and appropriate controls, were maintained for up to 30 days and
      assessed by light and scanning electron microscopy or immunolocalization of PCO
      markers (alpha-smooth muscle actin or fibronectin) or a marker for lens
      epithelial cell phenotype (Pax-6). RESULTS: In the absence of DEX, explants
      become multilayered and plaques that express PCO markers form. Cells tend to
      gather up into the plaques, leaving the surrounding lens capsule denuded. Changes
      in lens cell behavior with addition of DEX included rapid formation of long,
      needle-like cells, less extracellular matrix deposited on explant surface, and
      plaques surrounded by a monolayer of migratory cells. Immunolocalization
      confirmed that the latter were not normal lens epithelial cells. CONCLUSIONS:
      Lens cell behavior in this PCO model was significantly affected by inclusion of
      DEX, highlighting the possibility that its use as an anti-inflammatory at the
      time of cataract surgery may influence PCO development.

PMID- 15480303
TI  - Characterization of 3',5' cyclic nucleotide phosphodiesterase activity in Y79
      retinoblastoma cells: absence of functional PDE6.
AB  - PURPOSE: Previous studies identified rod photoreceptor cyclic GMP
      phosphodiesterase (PDE6) transcripts in the human Y79 retinoblastoma cell line.
      To assess the potential to utilize this cell line for structure/function studies
      of PDE6, we analyzed 3',5' cyclic nucleotide phosphodiesterase activity focusing
      on expression of PDE6. METHODS: DEAE-chromatography was used to fractionate PDE
      activity from Y79 cell homogenates. PCR was performed on cDNA generated from Y79
      cells and retina with PDE isoform specific primers. Western blots were performed
      with antibodies to PDE1, PDE4, or rod PDE6. DNA sequencing and protein truncation
      tests were performed with plasmids containing the entire coding region of Y79 rod
      PDE6 transcripts. Proteasome mediated degradation of PDE6 subunits was analyzed
      with a pathway specific inhibitor. Polysome isolation was performed by
      fractionation on sucrose gradients followed by RT-PCR for the PDE6 transcripts.
      RESULTS: Of three peaks of PDE activity, peaks 1 and 2 were activated by
      Ca2+/calmodulin, inhibited by dipyridamole and zaprinast, and were reactive with
      a PDE1 antibody. Peak 3 hydrolyzed only cAMP and was rolipram sensitive,
      indicative of PDE4. Transcripts for rod and cone PDE6 isoforms were detected in
      Y79 total RNA, however PDE6 antibodies recognized only a single 99 kDa
      polypeptide from immunoprecipitated 35S labeled Y79 extracts. DNA sequencing of
      PDE6 alpha, beta, gamma, and PDE6 associated delta-subunit cDNA revealed some
      polymorphism, but no apparent mutations. Each of the PDE6 transcripts could be
      translated into protein of the correct length. The concentration of cGMP in the
      cells was greatly reduced in comparison to that reported in the photoreceptor
      cell. Addition of cyclic nucleotide analogues, zinc, or butyrate did not enhance
      the expression of PDE6. Transduction into Y79 cells of adenovirus expressing PDE6
      subunits failed to produce functional enzyme CONCLUSIONS: PDE1 and PDE4 enzyme
      activities predominate in Y79 cells. Despite the presence of PDE6 transcripts and
      the ability to translate each into protein in vitro, a functional PDE6 enzyme
      could not be detected. Attempts to enhance expression with cell culture or with
      introduction of virus expressing PDE6 were not successful. The results indicate
      that expression of a fully active stable PDE6 enzyme requires other post
      transcriptional events that do not occur or are inhibited in Y79 cells.

PMID- 15480305
TI  - Outpatient treatment of chronic obstructive pulmonary disease: comparisons with
      asthma.
AB  - Chronic obstructive pulmonary disease (COPD) is a progressive syndrome of
      expiratory airflow limitation caused by chronic inflammation of the airways and
      lung parenchyma. The airway inflammatory response in COPD is initiated by smoking
      in the overwhelming majority of cases, and chronic exposure to cigarette smoke
      initiates a series of events that cause damage to central airways, peripheral
      airways, and terminal airspaces, leading to physiologic and clinical
      abnormalities. The contrasting inflammatory phenotypes of asthma and COPD have
      important implications for clinical and physiologic manifestations of disease, as
      well as for therapy. The outpatient treatment of COPD differs from the approach
      used in asthma and can be divided into 3 subgroups: health care maintenance, drug
      therapy, and nondrug therapy. Smoking cessation, regular spirometry, and
      immunization are important components of health care maintenance. Drug therapy
      consists of optimal bronchodilator therapy supplemented, when necessary, with
      either inhaled corticosteroids or theophylline. Nondrug therapies include
      pulmonary rehabilitation, supplemental oxygen, and surgery.

PMID- 15480307
TI  - The role of activation-induced cytidine deaminase in antibody diversification,
      immunodeficiency, and B-cell malignancies.
AB  - Before exposure to antigen, antibodies with a wide diversity of antigen-binding
      sites are created by V(D)J rearrangement. After exposure to antigen, further
      diversification is accomplished by means of somatic hypermutation of the antibody
      variable region genes and class-switch recombination between the heavy-chain mu
      constant region and the downstream gamma, epsilon, and alpha constant region. The
      variable region mutations are responsible for the affinity maturation of the
      antibody response, whereas class-switch recombination enables the antibodies to
      be distributed throughout the body and to carry out different effector functions.
      Both somatic mutation and class switching require an enzyme called activation
      induced cytidine deaminase (AID) that converts deoxycytidines to deoxyuracils on
      single-stranded DNA. Genetic defects of AID in human subjects result in hyper-IgM
      syndrome type 2. The analysis of both mutant mice and immunodeficient patients
      has led to a better understanding of the mechanism of action and role of AID in
      immunity, as well as in the malignant transformation of B cells.

PMID- 15480309
TI  - The role of endogenous and exogenous AMP in asthma and chronic obstructive
      pulmonary disease.
AB  - Bronchial hyperresponsiveness is present in virtually all patients with asthma
      and in more than two thirds of patients with chronic obstructive pulmonary
      disease. Thus far, methacholine and histamine are usually used to measure
      bronchial hyperresponsiveness. Both are direct stimuli, because they act directly
      on airway smooth muscle. Another possible stimulus to measure bronchial
      hyperresponsiveness is AMP. AMP is an indirect stimulus, because it acts via the
      release of histamine and other mediators from immunologically primed mast cells.
      There is increasing interest in the role of AMP as a bronchoconstrictor stimulus
      because it has been suggested that the concentration of AMP causing the FEV 1 to
      decrease by 20% (PC 20 AMP) may be used as a noninvasive marker of airway
      inflammation. The aim of this article was to review the literature assessing
      AMP's value in asthma and chronic obstructive pulmonary disease.

PMID- 15480311
TI  - Corticotropin-releasing hormone deficiency increases allergen-induced airway
      inflammation in a mouse model of asthma.
AB  - BACKGROUND: Corticotropin-releasing hormone (CRH) is a major regulator of
      adrenocorticotropic hormone and the production of glucocorticoids by the adrenal
      gland. Abnormal regulation of CRH and endogenous glucocorticoids has been
      implicated in the pathogenesis of asthma. OBJECTIVE: We postulated that CRH
      deficiency could increase asthma severity by disrupting hypothalamus-pituitary
      adrenal axis function and the induction of glucocorticoids through inflammatory
      and physiologic stress. However, CRH is expressed by several types of immune
      cells and might be induced at sites of inflammation, where it has local
      immunostimulatory actions. Thus CRH deficiency could decrease asthma severity.
      METHODS: To test these possibilities, we subjected CRH-knockout mice to an
      ovalbumin-induced airway inflammation protocol that mimics many features of
      asthma. RESULTS: CRH-knockout mice had an increase in airway inflammation of
      approximately 80% to 300% and an increase in goblet cell hyperplasia of
      approximately 70% compared with wild-type mice. In contrast, IgE induction was
      unaffected by CRH deficiency. The increased inflammation in knockout mice was
      associated with increased tissue resistance, elastance, and hysteresivity. Levels
      of IL-4, IL-5, IL-13, RANTES, IFN-gamma, and eotaxin were all increased in
      knockout mice. Serum corticosterone levels were decreased in knockout mice and
      might account for some of the differences between knockout and wild-type mice.
      CONCLUSION: We conclude that CRH deficiency disrupts endogenous glucocorticoid
      production and enhances allergen-induced airway inflammation and lung mechanical
      dysfunction in mice. Thus inherited or acquired CRH deficiency could increase
      asthma severity in human subjects.

PMID- 15480312
TI  - Breast-feeding reduces the risk of asthma during the first 4 years of life.
AB  - BACKGROUND: The evidence for a preventive effect of breast-feeding on asthma and
      other allergic diseases in childhood is inconclusive. OBJECTIVE: The aim of this
      study was to investigate the effect of breast-feeding on asthma and sensitization
      to airborne allergens among children up to 4 years of age. METHODS: A birth
      cohort of 4089 children was followed. Exposure data were collected at 2 months
      and 1 year of age. The total dose of breast milk was estimated by combining
      periods of exclusive and partial breast-feeding. Outcomes data were collected at
      1, 2, and 4 years of age. The response rate at 4 years was 90%, and 73%
      participated in a clinical investigation, including blood sampling for analysis
      of specific IgE and lung function testing. Children with onset of wheeze during
      lactation (n=217) were excluded in some of the analyses to avoid disease-related
      modification of exposure. RESULTS: Exclusive breast-feeding for 4 months or more
      reduced the risk of asthma at the age of 4 years (odds ratio [OR], 0.72; 95% CI,
      0.53-0.97), irrespective of sensitization to common airborne allergens ( P=.72).
      Excluding children with wheeze during lactation tended to strengthen the risk
      estimate (OR, 0.64; 95% CI, 0.46-0.88). A duration of 3 months or more of partial
      breast-feeding seemed to offer additional protection; exclusive breast-feeding
      for 3 to 4 months combined with partial breast-feeding for 3 months or more
      resulted in an OR of 0.44 (95% CI, 0.21-0.87). The effects tended to be stronger
      in children without heredity for allergy ( P interaction=.36). CONCLUSION: Breast
      feeding reduces the risk of asthma during the first 4 years of life.

PMID- 15480313
TI  - Effects of inhaled corticosteroids on exhaled leukotrienes and prostanoids in
      asthmatic children.
AB  - BACKGROUND: Lipid mediators play an important pathophysiologic role in atopic
      asthmatic children, but their role in the airways of atopic nonasthmatic children
      is unknown. OBJECTIVE: We sought (1) to measure leukotriene (LT) E 4 , LTB 4 , 8
      isoprostane, prostaglandin E 2 , and thromboxane B 2 concentrations in exhaled
      breath condensate in atopic asthmatic and atopic nonasthmatic children; (2) to
      measure exhaled nitric oxide (NO) as an independent marker of airway
      inflammation; and (3) to study the effect of inhaled corticosteroids on exhaled
      eicosanoids. METHODS: Twenty healthy children, 20 atopic nonasthmatic children,
      30 steroid-naive atopic asthmatic children, and 25 atopic asthmatic children
      receiving inhaled corticosteroids were included in a cross-sectional study. An
      open-label study with inhaled fluticasone (100 microg twice a day for 4 weeks)
      was undertaken in 14 steroid-naive atopic asthmatic children. RESULTS: Compared
      with control subjects, exhaled LTE 4 ( P <.001), LTB 4 ( P <.001), and 8
      isoprostane ( P <.001) levels were increased in both steroid-naive and steroid
      treated atopic asthmatic children but not in atopic nonasthmatic children (LTE 4
      , P=.14; LTB 4 , P=.23; and 8-isoprostane, P=.52). Exhaled NO levels were
      increased in steroid-naive atopic asthmatic children ( P <.001) and, to a lesser
      extent, in atopic nonasthmatic children ( P <.01). Inhaled fluticasone reduced
      exhaled NO (53%, P <.0001) and, to a lesser extent, LTE 4 (18%, P <.01) levels
      but not LTB 4 , prostaglandin E 2 , or 8-isoprostane levels in steroid-naive
      asthmatic children. Conclusions Exhaled LTE 4 , LTB 4 , and 8-isoprostane levels
      are increased in atopic asthmatic children but not in atopic nonasthmatic
      children. In contrast to exhaled NO, these markers seem to be relatively
      resistant to inhaled corticosteroids.

PMID- 15480314
TI  - Systemic effects of allergen exposure on blood basophil IL-13 secretion and
      FcepsilonRIbeta.
AB  - BACKGROUND: Airway allergen challenge studies have shown the upregulation of
      cytokines in local airway tissues and distal effects on bone marrow precursors
      for eosinophils and basophils. OBJECTIVE: We investigated whether local
      intranasal allergen challenge alters the phenotype of circulating basophils to a
      primed state. METHODS: Ten subjects with allergic rhinitis were challenged with
      allergen by means of intranasal spray on 3 sequential days. Basophils were
      isolated from subjects before challenge and 3, 24, and 96 hours after the third
      allergen challenge. Basophils were compared before challenge and after the last
      allergen challenge for levels of FcepsilonRIbeta protein by means of Western
      blotting and for FcepsilonRIbeta mRNA expression by means of real-time PCR.
      Basophils were also compared with regard to spontaneous secretion of IL-4 and IL
      13. RESULTS: Basophil FcepsilonRIbeta protein levels increased in 5 of 6 subjects
      after allergen challenge relative to before challenge. Likewise, basophil
      FcepsilonRIbeta mRNA levels increased a median of 2-fold after the last challenge
      relative to before challenge ( P=.007, n=9). IL-13 protein was detected in
      supernatants of 7 of 9 subjects' basophil-enriched cultures after the last
      challenge compared with 3 of 9 basophil-enriched cultures before challenge
      (median, 6.2 vs 0 pg/mL; P=.058). IL-4 was not detected in any culture
      supernatant. CONCLUSION: Intranasal allergen challenge transiently activates
      circulating basophils by increasing expression of the FcepsilonRIbeta subunit and
      spontaneous IL-13 secretion. Because FcepsilonRIbeta is an amplifier of
      FcepsilonRI-mediated responses and IL-13 is proinflammatory, these findings
      support a primed basophil functional state and demonstrate a systemic effect of
      local allergen challenge that could contribute in exacerbating allergic
      reactions.

PMID- 15480316
TI  - Gene expression profiles in human nasal polyp tissues studied by means of DNA
      microarray.
AB  - BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of the
      sinuses. Its pathogenesis is unknown. DNA microarray analysis allows simultaneous
      measurement of expression of thousands of genes in the same tissue sample and
      might help to identify gene alterations in various disorders. OBJECTIVE: We
      sought to screen for disease-related genes in NP by using DNA microarrays and to
      validate the altered expression of selected genes at the mRNA and protein level.
      METHODS: Expression microarrays containing approximately 10,500 genes were used
      to compare individual gene profiles of NP samples (n=10) and normal mucosal
      samples obtained from sphenoid sinuses in patients undergoing pituitary surgery
      (n=4). Four of the 5 most upregulated, and the single most downregulated, genes
      were retested by means of quantitative RT-PCR and immunohistochemistry in a
      different set of NP and normal mucosal samples obtained from the ethmoid and
      sphenoid sinuses. RESULTS: Compared with normal sinus tissue, 192 genes were
      upregulated at least 2-fold, and 156 genes were downregulated by at least 50% in
      NP samples (approximately 3% of genes evaluated). Four of the top 5 overexpressed
      genes (statherin, 48.0-fold; prolactin-induced protein [PIP] , 24.9-fold;
      lactoferrin, 26.6-fold; and deleted in malignant brain tumor 1 [DMBT1] , 30.3
      fold) and the most underexpressed gene (Clara cell 10-kd protein [CC10] , -20.1
      fold) were selected and retested by means of quantitative RT-PCR and
      immunohistochemical staining. Quantitative RT-PCR and immunohistochemical
      staining confirmed the differential expression of all except statherin in NP
      tissue. CONCLUSION: DNA microarrays can provide new insight into the possible
      pathophysiologic processes involved in NP.

PMID- 15480315
TI  - Inducible costimulator-positive T cells are required for allergen-induced local B
      cell infiltration and antigen-specific IgE production in lung tissue.
AB  - BACKGROUND: Airway inflammation plays a critical role in the pathogenesis of
      asthma. In susceptible individuals, airway allergen exposure results in the
      recruitment of inflammatory cells into lung tissue, leading to a local
      inflammatory response. Central to the induction and regulation of this process
      are T lymphocytes. OBJECTIVE: Blocking of the newly discovered costimulatory T
      cell molecule inducible costimulator (ICOS) with monoclonal antibodies was shown
      to ameliorate allergic airway inflammation in models of murine asthma. Although
      these observations indirectly support an association between ICOS and the
      development of allergic inflammation, the role of the ICOS + T cell in the
      pathogenesis of allergic airway disease remains unclear. METHODS: We used an
      adoptive transfer model to analyze further the role of antigen-specific ICOS + T
      cells during the effector phase of allergic airway inflammation. In vitro
      stimulated CD4 + T cells from mice transgenic for an ovalbumin-specific T-cell
      receptor (DO11.10) were sorted into ICOS-enriched and ICOS-depleted T-cell
      fractions and transferred into BALB/c recipient mice. RESULTS: Transfer of the
      ICOS-enriched T-cell population followed by allergen airway challenges induced
      pronounced infiltration of recipient T and B cells and local production of
      allergen-specific IgE by intrapulmonary plasma cells. In contrast, transfer of
      the ICOS-depleted T-cell fraction resulted in the recruitment of significantly
      lower numbers of B cells and no local IgE production. CONCLUSION: These data
      indicate that expression of ICOS defines a subset of T effector cells that are
      required for B-cell infiltration and local IgE production in lung tissues on
      allergen airway exposure.

PMID- 15480317
TI  - TGF-beta differentially regulates TH2 cytokine-induced eotaxin and eotaxin-3
      release by human airway smooth muscle cells.
AB  - BACKGROUND: Human airway smooth muscle cells (HASMs) are involved in the
      pathogenesis of asthma. By producing chemokines, HASMs play a role in the
      inflammatory processes observed in this disease. Eotaxin, eotaxin-2, and eotaxin
      3 are important chemoattractants for eosinophils, and these chemokines are
      expressed during different phases of the allergic reaction. TH2 cytokines and TGF
      beta can be found in increased levels in patients with asthma, and these
      cytokines may be involved in the regulation of chemokine expression. OBJECTIVE:
      The aim of this study was to determine the effect of TH2 cytokines and TGF-beta
      on the regulation of expression of eotaxin, eotaxin-2, and eotaxin-3 by HASMs.
      METHODS: HASMs were incubated for 24 hours with IL-4, IL-13, TGF-beta1, or
      combinations of these cytokines. Protein and mRNA levels of eotaxin and eotaxin-3
      were evaluated by sandwich ELISA and reverse transcriptase-PCR. RESULTS: IL-4 and
      IL-13 induced mRNA and protein for both eotaxin and eotaxin-3. Eotaxin-2 mRNA and
      protein were not detected in HASMs. TGF-beta alone did not induce expression of
      the eotaxins. However, in combination with IL-4 or IL-13, TGF-beta enhanced
      eotaxin production and inhibited TH2 cytokine-induced eotaxin-3 production.
      CONCLUSION: TGF-beta differentially regulates TH2 cytokine-induced eotaxin and
      eotaxin-3 release.

PMID- 15480318
TI  - Nasal mucosal immunoexpression of the mast cell chemoattractants TGF-beta,
      eotaxin, and stem cell factor and their receptors in allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis is characterized by the epithelial accumulation of
      cells, particularly mast cells and eosinophils. There is little information
      relating to the chemotaxins responsible for mast cell epithelial accumulation in
      this disease. OBJECTIVE: Expression of the mast cell chemoattractants TGF-beta,
      eotaxin, and stem cell factor and their receptors was investigated in tissue
      sections from biopsy specimens obtained from patients with naturally occurring
      allergic rhinitis. METHODS: Specific immunohistochemical staining was performed
      on thin sections of inferior turbinate biopsy specimens from patients with
      perennial and seasonal allergic rhinitis and, for comparison, from nonatopic and,
      where relevant, atopic healthy volunteers without rhinitis. Sequential staining
      of adjacent 2-microm sections was undertaken to colocalize TGF-beta receptors to
      mast cells. RESULTS: Evidence was found of significantly increased epithelial
      immunoreactivity for TGF-beta1, TGF-beta2, TGF-beta3, TGF-beta receptor I, TGF
      beta receptor II, and TGF-beta receptor III in patients with perennial and
      seasonal allergic rhinitis compared with that seen in healthy control subjects.
      TGF-beta receptors I and II were found to colocalize to mast cells. Eotaxin
      epithelial immunoreactivity was significantly increased in the perennial group,
      although there were no corresponding disease-related differences found in
      relation to CCR-3 immunoreactivity at this site. There was no increase in stem
      cell factor immunoreactivity within the epithelium in naturally occurring
      disease. Significant correlations were found between epithelial immunoreactivity
      for TGF-beta1, TGF-beta2, TGF-beta receptor I, TGF-beta receptor II, and the
      number of epithelial mast cells. CONCLUSION: These findings of enhanced
      epithelial TGF-beta immunoreactivity in patients with rhinitis, the correlation
      with intraepithelial mast cell numbers, and the colocalization of TGF-beta
      receptors to mast cells suggest that the epithelial expression of TGF-beta might
      represent an important biologic process involved in either the recruitment or
      retention of mast cells within the epithelium in naturally occurring allergic
      rhinitis.

PMID- 15480319
TI  - Three-year outcomes of dietary fatty acid modification and house dust mite
      reduction in the Childhood Asthma Prevention Study.
AB  - BACKGROUND: Two factors thought to influence the risk of asthma are the promoting
      effect of sensitization to house dust mites and the preventive effect of
      increased omega-3 fatty acids. Although house dust mite allergen avoidance has
      been used as a preventive strategy in several trials, the effect of omega-3 fatty
      acid supplementation in the primary prevention of asthma and allergic disease is
      not known. OBJECTIVE: To measure the effects of dietary supplementation with
      omega-3 fatty acids and house dust mite allergen avoidance in children with a
      family history of asthma. METHODS: A total of 616 children at high risk of asthma
      were enrolled antenatally in a randomized controlled trial, and 526 children
      remained in the trial at age 3 years. The outcomes were symptoms of allergic
      disease and allergen sensitization. RESULTS: There was a significant 10.0% (95%
      CI, 3.7-16.4) reduction in the prevalence of cough in atopic children in the
      active diet group ( P=.003; number needed to treat, 10) but a negligible 1.1%
      (95% CI, -7.1 to 9.5) reduction cough among nonatopic children. There was a 7.2%
      (95% CI, 10.11-14.3) reduction in sensitization to house dust mite in the active
      allergen avoidance group ( P=.05; number needed to treat, 14). No significant
      differences in wheeze were found with either intervention. CONCLUSION: These
      results suggest that our interventions, designed to be used in simple public
      health campaigns, may have a role in preventing the development of allergic
      sensitization and airways disease in early childhood. This offers the prospect of
      reducing allergic disease in later life.

PMID- 15480320
TI  - Dynamics of COX-2 in nasal mucosa and nasal polyps from aspirin-tolerant and
      aspirin-intolerant patients with asthma.
AB  - BACKGROUND: Only dynamic studies can elucidate the discrepancies concerning the
      expression of the inducible COX-2 gene in inflammatory airway diseases.
      OBJECTIVES: To quantify the expression and spontaneous regulation of COX-1 and
      COX-2 mRNAs in nasal polyps and nasal mucosa by real-time PCR. METHODS: Nasal
      polyps were obtained from 16 aspirin-tolerant patients with asthma/rhinitis
      (ATAR) and 18 aspirin-intolerant patients with asthma/rhinitis (AIAR) undergoing
      nasal polypectomy. Nasal mucosa was obtained from 12 subjects undergoing nasal
      corrective surgery. All specimens were cut into 3 pieces. One was immediately
      snap-frozen in liquid nitrogen, and the remaining 2 were left at room temperature
      for 30 or 60 minutes before freezing. Data are presented as medians and 25th to
      75th percentiles of 10 6 cDNA molecules/microg total RNA. RESULTS: Baseline COX-2
      mRNA levels were significantly lower in both ATAR (0.45; 0.13-1.20; P <.05) and
      AIAR (0.24; 0.12-0.41; P <.001) nasal polyps than in nasal mucosa (1.35; 0.52
      3.90). COX-2 mRNA expression did not change over time in nasal mucosa but
      increased significantly in ATAR nasal polyps ( P <.05), reaching similar levels
      to nasal mucosa after 60 minutes. In contrast, COX-2 mRNA showed no significant
      change over time in AIAR nasal polyps. COX-1 mRNA was higher in nasal polyps than
      in nasal mucosa, and its expression was not modified over time in any group of
      patients. CONCLUSION: These results suggest differential kinetics of COX-2 mRNA
      between nasal mucosa and nasal polyps. AIAR nasal polyps appear to have a greater
      abnormality of the COX-2 pathway than ATAR.

PMID- 15480321
TI  - Migration and accumulation of eosinophils toward regional lymph nodes after
      airway allergen challenge.
AB  - BACKGROUND: Eosinophils play a major role in allergic airway inflammation because
      of their ability to release toxic mediators. In addition, they are able to
      migrate toward draining thoracic lymph nodes (TLNs) after intratracheal
      administration, where they can function as antigen-presenting cells. OBJECTIVE:
      In this study, we evaluated in vivo eosinophil migration toward the TLN after
      allergen sensitization and analyzed expression of molecules involved in antigen
      presentation. METHODS: Mice were sensitized by intraperitoneal injection of
      ovalbumin on days 1 and 10 and challenged once intranasally with ovalbumin on day
      20. The kinetics of eosinophilia was evaluated in blood, lung tissue homogenate,
      bronchoalveolar lavage fluid, and TLN. Cell surface staining was analyzed by flow
      cytometry. RESULTS: The kinetics of eosinophil recruitment was similar in TLN,
      lung tissue, and blood, beginning at 12 hours and peaking at 48 hours after
      allergen challenge. Approximately 70% of TLN eosinophils expressed MHC class II
      molecules, compared with less than 25% in blood and lungs. Moreover, TLN
      eosinophils expressed higher levels of MHC class II and CD86 compared with blood
      and lung eosinophils. Most eosinophils expressed CD80 and CD54, whereas only a
      few eosinophils expressed CD40. Eosinophils in lungs and TLN appeared to be
      activated with lower CD62-ligand expression compared with blood eosinophils.
      CONCLUSION: The presence of eosinophils with a different phenotype in the TLN at
      early time points after allergen challenge of sensitized mice supports their
      capacity to serve as antigen-presenting cells, sustaining allergic/inflammatory
      responses in the airways.

PMID- 15480322
TI  - Major quantitative trait locus for eosinophil count is located on chromosome 2q.
AB  - BACKGROUND: Eosinophils are granulocytic white blood cells implicated in asthma
      and atopic disease. The degree of eosinophilia in the blood of patients with
      asthma correlates with the severity of asthmatic symptoms. Quantitative trait
      loci (QTL) linkage analysis of eosinophil count may be a more powerful strategy
      of mapping genes involved in asthma than linkage analysis using affected relative
      pairs. OBJECTIVE: To identify QTLs responsible for variation in eosinophil count
      in adolescent twins. METHODS: We measured eosinophil count longitudinally in 738
      pairs of twins at 12, 14, and 16 years of age. We typed 757 highly polymorphic
      microsatellite markers at an average spacing of approximately 5 centimorgans
      across the genome. We then used multipoint variance components linkage analysis
      to test for linkage between marker loci and eosinophil concentrations at each age
      across the genome. RESULTS: We found highly significant linkage on chromosome
      2q33 in 12-year-old twins (logarithm of the odds=4.6; P=.000002) and suggestive
      evidence of linkage in the same region in 14-year-olds (logarithm of the
      odds=1.0; P=.016). We also found suggestive evidence of linkage at other areas of
      the genome, including regions on chromosomes 2, 3, 4, 8, 9, 11, 12, 17, 20, and
      22. CONCLUSION: A QTL for eosinophil count is present on chromosome 2q33. This
      QTL might represent a gene involved in asthma pathophysiology.

PMID- 15480323
TI  - Randomized controlled trial of high-dose sublingual immunotherapy to treat
      seasonal allergic rhinitis.
AB  - BACKGROUND: Seasonal allergic rhinitis is common and troublesome. Sublingual
      immunotherapy (SLIT) has been proposed as an alternative to injection
      immunotherapy and might offer some advantages if it were effective and practical
      in a community setting. OBJECTIVES: To assess the efficacy and side-effect
      profile of SLIT in patients with summer hay fever uncontrolled on current
      standard medication. To assess the feasibility of delivering SLIT in a United
      Kingdom general practice setting. METHODS: Double-blind, placebo-controlled study
      in 186 patients with severe summer hay fever identified from 16 United Kingdom
      general practices. After a baseline year to ensure balanced groups, subjects were
      randomized, and SLIT was given for 1 or 2 years and compared with placebo. The
      principal outcome measure was symptoms as recorded on diary cards. Secondary
      criteria were skin and conjunctival reactivity, allergen-specific IgE and IgG 4 ,
      and the frequency and severity of adverse effects. RESULTS: One hundred thirty
      six subjects completed the study. After 1 year, no significant differences were
      found between actively treated subjects and the placebo group. After the second
      year of therapy, subjects who had received 2 years treatment were 6.8 times more
      likely to show a reduction in nose running (P <.001) and 2.4 times more likely to
      have reduced sneezing (P <.05) compared with subjects in the placebo group.
      Benefits for nasal blockage were found at the peak pollen season and were similar
      in both actively treated groups. CONCLUSION: Sublingual immunotherapy can be
      given successfully and safely in the community. High-dose SLIT has beneficial
      effects on nasal symptoms during the peak pollen season in patients with severe
      seasonal allergic rhinitis. At least 2 years of treatment with SLIT is required
      to show a benefit.

PMID- 15480324
TI  - Levocetirizine improves quality of life and reduces costs in long-term management
      of persistent allergic rhinitis.
AB  - BACKGROUND: Allergic Rhinitis and its Impact on Asthma in collaboration with the
      World Health Organization initiative reclassified allergic rhinitis, like asthma,
      by duration and severity. The Xyzal in Persistent Rhinitis Trial is the first
      large, long-term clinical trial studying patients with persistent rhinitis as
      defined by Allergic Rhinitis and its Impact on Asthma. OBJECTIVES: Two primary
      objectives were defined: comparison of the Rhinoconjunctivitis Quality of Life
      Questionnaire overall score and Total 5 Symptoms Score (rhinorrhea, sneezing,
      nasal congestion, and nasal and ocular pruritus) over a period of 4 weeks between
      levocetirizine 5 mg and placebo. Secondary endpoints included similar evaluations
      at 1 week and 3, 4.5, and 6 months, summary scores for a general health status
      questionnaire (Medical Outcomes Survey Short Form 36), a pharmacoeconomic
      assessment, comorbidities, and a safety evaluation. METHODS: The Xyzal in
      Persistent Rhinitis Trial was a 6-month double-blind, placebo-controlled,
      multicenter, multinational trial in 551 patients. Adults with persistent rhinitis
      sensitized to both grass pollen and house dust mite were randomized to receive
      levocetirizine 5 mg/d or placebo. RESULTS: A total of 421 patients completed the
      full study. Levocetirizine significantly improved both the Rhinoconjunctivitis
      Quality of Life Questionnaire overall score and the Total 5 Symptoms Score from
      week 1 to 6 months (all P values <.001). Medical Outcomes Survey Short Form 36
      summary scores were also improved in the levocetirizine group compared with the
      placebo group. Treatment cessation because of lack of effect, comorbidities, and
      overall costs of disease, and comorbidities per working patient per month (160.27
      vs 108.18) were lower in the levocetirizine group. CONCLUSION: Levocetirizine was
      shown to improve quality of life and symptoms and to decrease the overall costs
      of the disease over the 6-month treatment period.

PMID- 15480325
TI  - Health-related quality of life in adult rhinitis: the role of perceived control
      of disease.
AB  - BACKGROUND: Factors affecting health-related quality of life (HRQOL) in adult
      rhinitis have not been well described. OBJECTIVE: To understand how symptom
      severity, physical functioning, psychological distress, and perceived control of
      disease relate to HRQOL in a population-based sample of adults with rhinitis.
      METHODS: We conducted telephone interviews in 109 adults with rhinitis recruited
      via random digit dialing. We assessed HRQOL by using the Rhinosinusitis
      Disability Index, physical functioning by using the physical component score of
      the Short Form-12, and psychological distress by using the Center for
      Epidemiologic Studies Depression Scale. To evaluate the role of patient-perceived
      control of disease in rhinitis, we developed a new 8-item instrument, the
      Perceived Control of Rhinitis Questionnaire. RESULTS: Lower HRQOL correlated with
      greater symptom severity ( r=0.57), poorer physical functioning ( r=-0.41),
      greater psychological distress ( r=0.44), and less perceived control ( r=-0.53).
      In a multivariate model, symptom severity ( P < .001), psychological distress ( P
      <.001), and perceived control ( P <.001) were all independent predictors of
      HRQOL. Adding functional and psychosocial measures to a base model with
      demographics and disease severity explained an additional 26% of variance in
      HRQOL. CONCLUSIONS: Although disease severity is an important factor in HRQOL,
      psychosocial factors, such as perceived control of disease, explain a substantial
      amount of the variability in HRQOL among adults with rhinitis.

PMID- 15480326
TI  - Coseasonal sublingual immunotherapy reduces the development of asthma in children
      with allergic rhinoconjunctivitis.
AB  - BACKGROUND: We wondered whether short-term coseasonal sublingual immunotherapy
      (SLIT) can reduce the development of asthma in children with hay fever in an open
      randomized study. OBJECTIVE: We sought to determine whether SLIT is as effective
      as subcutaneous immunotherapy in reducing hay fever symptoms and the development
      of asthma in children with hay fever. METHODS: One hundred thirteen children aged
      5 to 14 years (mean age, 7.7 years) with hay fever limited to grass pollen and no
      other clinically important allergies were randomized in an open study involving 6
      Italian pediatric allergy centers to receive specific SLIT for 3 years or
      standard symptomatic therapy. All of the subjects had hay fever symptoms, but at
      the time of study entry, none reported seasonal asthma with more than 3 episodes
      per season. Symptomatic treatment was limited to cetirizine, loratadine, nasal
      budesonide, and salbutamol on demand. The hay fever and asthma symptoms were
      quantified clinically. RESULTS: The actively treated children used less
      medication in the second and third years of therapy, and their symptom scores
      tended to be lower. From the second year of immunotherapy, subjective evaluation
      of overall allergy symptoms was favorable in the actively treated children.
      Development of asthma after 3 years was 3.8 times more frequent (95% confidence
      limits, 1.5-10.0) in the control subjects. CONCLUSIONS: Three years of coseasonal
      SLIT improves seasonal allergic rhinitis symptoms and reduces the development of
      seasonal asthma in children with hay fever.

PMID- 15480327
TI  - Clinical effectiveness of a mite allergen-impermeable bed-covering system in
      asthmatic mite-sensitive patients.
AB  - BACKGROUND: Exposure to allergens plays a role in the development of bronchial
      hyperresponsiveness and in the chronic inflammatory response seen in asthmatic
      patients. House dust mites (HDMs) are an important source of allergen. Reduction
      of these allergens might lead to better lung function and reduction of asthma
      symptoms. OBJECTIVE: The effect of HDM-impermeable covers on HDM allergen levels,
      peak flow values, and asthma symptoms were measured. Therefore a randomized
      clinical trial was carried out. METHODS: Fifty-two allergic asthmatic patients
      were randomly allocated to use the HDM-impermeable or placebo covers. During the
      study period, daily peak flow and asthma symptom scores were recorded. Dust
      samples were taken from the mattresses. RESULTS: We observed a significant
      reduction in HDM allergen levels on the mattresses after encasing them with HDM
      impermeable covers (reduction of 87% of Der p 1 in micrograms per gram of dust; P
      <.001). Baseline symptoms were so low that no improvement could be established.
      Morning peak expiratory flow is significantly higher in the intervention group
      compared with that seen in the placebo group during the study period (beta=20.2;
      P <.01). CONCLUSIONS: HDM-impermeable covers significantly decreased the level of
      HDM allergens. Furthermore, morning peak flow was significantly increased during
      the intervention period. This study indicates that HDM allergen-avoidance
      measures might have beneficial effects on allergen reduction and asthma outcome.

PMID- 15480328
TI  - Adherence logger for a dry powder inhaler: a new device for medical adherence
      research.
AB  - BACKGROUND: Adherence to inhaled steroid regimens is frequently poor. Finding
      ways to improve adherence depends on the ability to measure time and date of
      inhaler use reliably and to detect deliberate dose dumping. There is no such
      monitor for the popular new dry powder inhalers. OBJECTIVE: To develop and test
      an electronic monitor for a dry powder inhaler that will provide information on
      the time and date of use. METHODS: An electronic adherence monitor for the Advair
      Diskus dry powder inhaler was developed and tested. In this device, inhaler use
      is determined by detecting and recording the motion of the drug delivery lever in
      the inhaler with a magnetic sensor. An additional electronic interface and
      software were also developed to allow the adherence data to be uploaded to a
      computer for display and analysis. RESULTS: System and reliability tests
      involving multiple-day and repeated-use tests of the adherence monitor
      demonstrate the overall performance and reliability of the device, and
      specifically its ability to record the time and date of dose delivery. In the
      repeated-use test, 300 successive actuations of the dose delivery lever were
      correctly sensed and recorded without error. CONCLUSION: The simple-to-use, low
      cost, reusable adherence monitor accurately records time and date of inhaler use
      and thus allows clinical monitoring and adherence studies in patients using the
      Advair Diskus dry powder inhaler. The same technology should be adaptable to
      other dry powder inhalers, including the Pulmicort Tubuhaler and the Symbicort
      Tubuhaler.

PMID- 15480329
TI  - Stinging insect hypersensitivity: a practice parameter update.

PMID- 15480330
TI  - Reduced dermal infiltration of cytokine-expressing inflammatory cells in atopic
      dermatitis after short-term topical tacrolimus treatment.
AB  - BACKGROUND: In several clinical studies, topical calcineurin inhibitors have been
      shown to be effective in the treatment of atopic dermatitis (AD). They target
      signaling pathways that control gene expression, particularly the expression of
      cytokines. OBJECTIVE: We examined the cellular infiltrate in skin lesions of 10
      patients with AD and characterized the cytokine pattern expressed by the
      infiltrating cells before and after short-term topical therapy with tacrolimus 1%
      ointment. METHODS: Skin biopsies were examined for histologic alterations
      (hematoxylin and eosin staining), composition of the cellular inflammatory
      infiltrate (immunofluorescence), and cytokine expression (ribonuclease protection
      assay, ELISA, immunofluorescence) before as well as 1 and 3 weeks after
      initiation of tacrolimus therapy. For comparison, biopsies from nonlesional AD
      and normal skin were analyzed. Systemic immunologic effects were assessed by
      analyzing peripheral blood leukocytes (immunofluorescence) as well as in vitro
      stimulated pan-T-cell cytokine production (ELISA). RESULTS: All patients showed a
      significant improvement of their skin lesions associated with a marked regression
      of spongiosis, acanthosis, and density of the cellular infiltrate in the dermis.
      The last was a result of reduced infiltration of T cells, B cells, and
      eosinophils. In contrast, the numbers of mast cells did not change. Moreover, the
      expression of the T H 2 cytokines IL-5, IL-10, and IL-13 in CD4 + T cells was
      reduced after therapy. Interestingly, tacrolimus therapy was also associated with
      a reduction of CD8 + T cells expressing the T H 1 cytokine IFN-gamma.
      Furthermore, the numbers of epidermal CD1a + dendritic cells increased after
      treatment. In the peripheral blood, a decrease of granulocytes (eosinophils and
      neutrophils) but no changes in the distribution of lymphocyte subpopulations were
      noticed. CONCLUSION: Topical tacrolimus treatment has anti-inflammatory effects
      on AD skin as indicated by reduced infiltration of cytokine expressing
      inflammatory cells. No evidence for drug-induced systemic immunosuppression was
      obtained.

PMID- 15480331
TI  - Novel plant pathogenesis-related protein family involved in food allergy.
AB  - BACKGROUND: Members belonging to 9 different families of plant pathogenesis
      related (PR) proteins have been identified as pollen and food allergens. However,
      no PR-1 protein, a family widely distributed throughout the plant kingdom, has
      been involved so far in allergic reactions. On the other hand, melon ranges among
      the most relevant fruits causing food allergy in some countries, but the majority
      of its allergens remain still unidentified. OBJECTIVE: We sought to identify
      melon allergens related to plant PR proteins. METHODS: A serum pool or individual
      sera from 17 patients with allergy to melon confirmed by means of double-blind,
      placebo-controlled food challenge were used to detect IgE binding proteins of
      extracts from melon pulp and juice. Cuc m 3 was isolated from melon juice by
      reverse-phase HPLC and characterized by means of N-terminal amino acid sequencing
      of internal peptides, matrix-assisted laser desorption/ionization mass
      spectrometry analysis, direct and inhibition ELISA assays, and skin prick tests.
      RESULTS: Cuc m 3 was a minor component of the melon juice, with a molecular
      weight of 16,097 d and a blocked N-terminus. N-terminal amino acid sequences of 3
      different peptides derived from endo-Lys C digestion (overall 41 residues) showed
      more than 60% of sequence identity with PR-1 proteins from grape and cucumber.
      Cuc m 3 bound IgE from 12 of 17 sera from patients allergic to melon and
      inhibited approximately 40% and 70% of the IgE binding to melon pulp and juice
      extracts, respectively. Positive skin prick test responses to purified Cuc m 3
      were found in 2 of 14 allergic patients. CONCLUSION: A new melon allergen
      belonging to the PR-1 protein family has been isolated and characterized. It is
      the first evidence of the involvement of this plant protein family in food
      allergy.

PMID- 15480332
TI  - Strong allergenicity of Pru av 3, the lipid transfer protein from cherry, is
      related to high stability against thermal processing and digestion.
AB  - BACKGROUND: Nonspecific lipid transfer proteins (nsLTPs) have been identified as
      major fruit allergens in patients from the Mediterranean area. Sensitization to
      nsLTPs is accompanied by severe reactions, possibly because of specific
      biophysical and biochemical properties of this allergen family. OBJECTIVE: To
      assess the protein stability and allergenic potency of nsLTP from fruits in
      comparison with birch pollen-related allergens from the same allergenic source.
      METHODS: Stability of natural and recombinant cherry allergens Pru av 3 (nsLTP),
      Pru av 1 (Bet v 1 homologue), and Pru av 4 (profilin) to pepsin digestion and to
      thermal processing and stability of allergens in skin prick test reagents was
      investigated by immunoblotting and/or circular dichroism spectroscopy. Moreover,
      allergenicity of processed and fresh fruits in regard to Pru av 1 and Pru av 3
      was analyzed by histamine release assays. RESULTS: Lipid transfer proteins showed
      the highest resistance to digestion by pepsin (rPru av 3 > rPru av 1 > rPru av
      4). Immunologically active Pru av 3 was detectable after 2 hours of digestion by
      pepsin, whereas IgE reactivity of Pru av 1 and Pru av 4 was abolished within less
      than 60 minutes. In contrast with Pru av 1, IgE reactivity to nsLTPs was not
      diminished in thermally processed fruits, and secondary structures of purified
      Pru av 3 were more resistant to heating. Moreover, nsLTPs were stable components
      in skin prick test reagents. Histamine release assays confirmed the strong
      allergenicity of nsLTPs, which was not affected by protease treatment or thermal
      processing of fruits. CONCLUSION: In contrast with birch pollen-related
      allergens, nsLTPs are highly stable to pepsin treatment and thermal processing
      and show higher allergenic potency. Therefore, nsLTPs have the potential to act
      as true food allergens, probably eliciting severe systemic reactions by reaching
      the intestinal mucosa in an intact and fully active form.

PMID- 15480333
TI  - Lipid transfer protein and vicilin are important walnut allergens in patients not
      allergic to pollen.
AB  - BACKGROUND: Walnut is the most common cause of allergic reactions to tree nuts,
      as reported by large population studies. Two major allergens of walnut have been
      identified up until now: a 2S albumin and a vicilin-like protein. OBJECTIVE: This
      study was designed to identify the walnut major allergens in the Italian
      population and to compare the walnut IgE-binding profile in patients with or
      without pollen allergy. METHODS: We selected 46 patients either with oral allergy
      syndrome confirmed by open oral challenge or with systemic symptoms after
      ingestion of walnut. These patients' sera were used for the immunoblotting of
      walnut extract; the identified allergens were purified by HPLC and sequenced. A
      peach-walnut cross-inhibition study was then performed. RESULTS: The only major
      allergen recognized by our study population was a 9-kd lipid transfer protein
      (LTP), recognized by 37 patients. Two other minor allergens of approximately 9-kd
      molecular weight, both belonging to the vicilin family, were recognized by 10
      patients. IgE binding to walnut LTP was completely inhibited by peach LTP.
      CONCLUSION: In Italian patients with walnut allergy confirmed by documented
      history of severe systemic reactions or by open oral food challenge, the major
      allergen is an LTP. The sensitization to this protein seems to be secondary to
      the sensitization to peach LTP, which acts as the primary sensitizer. LTP and
      vicilins were able to sensitize patients not allergic to pollen.

PMID- 15480335
TI  - Soy immunotherapy for peanut-allergic mice: modulation of the peanut-allergic
      response.
AB  - BACKGROUND: Allergen-specific immunotherapy (IT) is an effective therapeutic
      modality to prevent further anaphylactic episodes in patients with insect sting
      hypersensitivity and is being investigated for peanut allergy. So far, peanut
      specific IT has been unsuccessful because of the side effects of therapy. Soybean
      seed storage proteins share significant homology with the respective peanut
      allergens. OBJECTIVE: This study was undertaken in mice to investigate whether
      specific doses of soybean would desensitize peanut-allergic mice. METHODS:
      C3H/HeJ mice were sensitized to peanut with 3 intraperitoneal (IP) injections of
      crude peanut extract. The mice were desensitized by IP injections with either
      crude peanut or soybean extract for 4 weeks, 3 times a week. Controls included
      placebo desensitization with PBS and naive mice. After 2 weeks of rest, mice were
      challenged IP with crude peanut extract. Thirty minutes later, symptom scores and
      body temperatures were recorded. Serum immunoglobulins, peanut-induced splenocyte
      proliferation, and secreted cytokines were measured before and after
      desensitization. RESULTS: The clinical symptoms in the soybean- and peanut
      desensitized animals were markedly reduced compared with the placebo-treated
      mice. Specific IgG1 levels to crude peanut were significantly lower in the soy IT
      group than in the peanut IT group. The cellular response to crude peanut was also
      downregulated in the soy IT group, as shown by decreased peanut-specific
      stimulation indices and a cytokine profile skewed toward a T H 1 response.
      CONCLUSIONS: Soy IT can be used to desensitize/downregulate peanut-specific
      response in peanut-allergic mice and could provide a new therapeutic intervention
      for peanut allergy.

PMID- 15480336
TI  - High prevalence of autoimmune urticaria in children with chronic urticaria.
AB  - BACKGROUND: The etiology of chronic urticaria (CU) in childhood often remains
      unrecognized. Recently, in adults it has been shown that approximately 40% of
      patients with CU have autoimmune urticaria (AU); however, no data are available
      in children. OBJECTIVE: To determine the prevalence and possible risk factors for
      AU in children with CU. METHODS: Ninety-three consecutive children (52 male;
      median age, 7.8 years) with CU were evaluated for AU by means of autologous serum
      skin test (ASST) in all and serum-induced basophil histamine release (HR
      urticaria test) in 52. All other known causes of CU were excluded as appropriate.
      RESULTS: A cause for CU was identified in 44 children (47%), whereas 49 (53%)
      remained idiopathic. ASST and HR-urticaria test had positive results in 22 of 49
      (45%) and in 16 of 31 (52%) children with idiopathic CU compared with 1 of 44
      (2%) and 5 of 21 (24%) with CU of a known cause, respectively ( P <.00001;
      P=.09). Sensitivity, specificity, and positive and negative predictive values of
      the ASST for diagnosing AU are 78%, 85%, 74%, and 88%. The prevalence of AU in
      childhood is 31% (15/52; 95% CI, 24%-51%). None of the variables studied were
      predictive for development of AU. CONCLUSION: Our results demonstrate for the
      first time that children have the same ability as adults to produce functionally
      active autoantibodies directed against IgE or IgE receptor and that AU occurs in
      children in as many as 30% of cases. The addition of screening for AU
      dramatically decreases the rate of the idiopathic form from 52% to 20%.

PMID- 15480337
TI  - Hymenoptera venom protease allergens.
AB  - BACKGROUND: Recent studies have shown the presence of additional allergenic
      proteins in honeybee and paper wasp venoms. Both venoms contain serine protease
      enzymes. OBJECTIVE: We isolated and obtained complete sequences of honeybee and
      Mediterranean paper wasp venom proteases, both of which have significant IgE
      binding activity. The structures are compared with bumblebee venom protease.
      METHODS: Venom proteases were chromatographically isolated from venoms and
      partial amino acid sequences determined. RT-PCR and rapid amplification of cDNA
      ends methods were used to clone cDNA, and complete sequences were determined for
      honeybee and a paper wasp venom protease. RESULTS: The venom proteases are all
      serine proteases of the trypsin type. The honeybee protease contains a
      complement, embryonic sea urchin protein, bone morphogenetic protein interaction
      domain as well as a linker and propeptide sequence, and a unique methionine
      residue near the active site. It has IgE binding activity. The paper wasp
      protease is a single trypsin domain and is an important allergen. The framework
      residues are poorly conserved among honeybee, bumblebee, and paper wasp enzymes.
      CONCLUSIONS: The 3 venom serine proteases have significant IgE binding
      activities. The structures are poorly conserved even among the Apidae ,
      suggesting little cross-reactivity among the protein portions. The paper wasp
      venom proteases are important allergens.

PMID- 15480338
TI  - Subcutaneous immunoglobulins: alternative for the hypogammaglobulinemic patient?

PMID- 15480339
TI  - Children and adults with primary antibody deficiencies gain quality of life by
      subcutaneous IgG self-infusions at home.
AB  - BACKGROUND: A large number of children and adults with primary antibody
      deficiencies need lifelong IgG replacement therapy. It is mostly unknown what
      effect the choice of replacement therapy has on the patients' health-related
      quality of life (HRQOL) and treatment satisfaction (TS). OBJECTIVE: To
      investigate whether a switch from hospital-based intravenous IgG (IVIG) to home
      based subcutaneous IgG (SCIG) therapy would improve the HRQOL and TS. METHODS:
      Fifteen children (<14 years; hospital-based IVIG therapy at enrollment) and 32
      adults (> or =14 years; 22 on hospital-based IVIG and 10 on home-based SCIG
      therapy at enrollment) were included. Questionnaires were completed at baseline
      and at 6 and 10 months: the Child Health Questionnaire-Parental Form 50
      (children) or Short Form 36 (adults), the Life Quality Index, and questions
      regarding therapy preferences. RESULTS: The SCIG home therapy was reported to
      give better health (P=.001) and improved school/social functioning (P=.02) for
      the children, reduced emotional distress (P=.02) and limitations on personal time
      for the parents (P=.004), and fewer limitations on family activities (P=.002).
      Adults switching therapy reported improved vitality (P=.04), mental health (
      P=.05), and social functioning ( P=.01). Adults already on SCIG home therapy at
      enrollment retained high HRQOL and TS scores. The SCIG home therapy improved TS
      because it led to greater independence and better therapy convenience ( P <.05).
      The patients preferred the SCIG administration route and having the treatment at
      home. CONCLUSIONS: Home-based SCIG therapy improves several important aspects of
      HRQOL and provides the patients with primary antibody deficiencies and their
      families with greater independence and better control of the therapy situation
      and daily life. SCIG home therapy is an appreciated therapeutic alternative for
      adults and children in need of lifelong IgG replacement therapy.

PMID- 15480340
TI  - Modulation of allergic responses in mice by using biodegradable poly(lactide-co
      glycolide) microspheres.
AB  - BACKGROUND: Biodegradable poly(lactide- co -glycolide) (PLGA) microspheres are a
      promising carrier for vaccine delivery capable of maturing antigen-presenting
      cells to stimulate T-cell-mediated immune responses. However, the potential of
      microspheres to downregulate an allergic response in vivo is unknown. OBJECTIVE:
      The aim of this study was to determine whether microspheres could potentiate DNA
      vaccination against allergy and to evaluate the immunomodulatory properties of
      microspheres alone. METHODS: Mice were treated prophylactically with DNA-loaded
      plain PLGA microspheres before sensitization with phospholipase A2 (PLA2), the
      major allergen of bee venom. PLA2-specific IgG1, IgG2a, IgE in serum were
      measured for 8.5 months, and splenocyte proliferative responses and cytokine
      profiles were determined. Protection against anaphylaxis was evaluated after
      injection of an otherwise lethal dose of PLA2. RESULTS: Phospholipase A2-specific
      IgG1 and IgG2a production turned out to be 2 times higher using cationic
      microspheres compared with anionic microspheres, but was not influenced by the
      presence of DNA. In contrast, reduction in IgE production and T-cell
      hyporesponsiveness were observed with all microsphere formulations. Recall
      challenge with PLA2 triggered combined expression of both IL-4 and IFN-gamma,
      together with sustained expression of IL-10 that can explain the protective
      effect against anaphylaxis. CONCLUSION: Our data suggest a dual mechanism that
      does initially rely on a TH2 to TH1 immune deviation and then on IL-10-mediated
      suppression. This is the first physiological demonstration that plain PLGA
      microspheres can induce tolerance in mice for as long as 6 months
      postsensitization.

PMID- 15480341
TI  - Prevention of long-term IgE antibody production by gene gun-mediated DNA
      vaccination.
AB  - BACKGROUND: Vaccination with allergen-encoding DNA represents a promising
      approach for the treatment of allergic diseases. OBJECTIVE: In a mouse model of
      type I allergy, we analyzed the ability of biolistic transfection to inhibit
      antigen-specific IgE production and to modulate TH2 responses. METHODS: BALB/c
      mice were vaccinated by means of gene gun-mediated DNA immunization with plasmid
      vector pCMV-betaGal, encoding beta-galactosidase as a model allergen.
      Subsequently, mice were immunized by means of repeated intraperitoneal injection
      of beta-galactosidase adsorbed to the adjuvant aluminum hydroxide. Development of
      IgE, IgG1, and IgG2a antibody titers during the course of immunization was
      followed, and anaphylactic potential of sera was determined by using RBL-2H3
      degranulation assay. Spleen cells of vaccinated mice and unvaccinated control
      animals were stimulated in vitro to analyze cytokine production and induction of
      CD8 + effector T cells. RESULTS: Gene gun-mediated DNA immunization with pCMV
      betaGal very efficiently prevented IgE antibody production on a long-term basis.
      Concomitantly, IgG1 antibody levels in vaccinated mice were strongly reduced,
      whereas IgG2a antibody production was increased. Analysis of cytokine profiles
      indicated immune deviation from a TH2-biased response in control mice toward a
      mixed TH1/TH2 response in vaccinated mice. In addition, substantial numbers of
      IFN-gamma-producing CD8 + effector T cells were found in vaccinated mice.
      CONCLUSION: Gene gun-mediated DNA vaccination prevents the induction of long
      lasting IgE antibody production.

PMID- 15480342
TI  - IL-17A augments TNF-alpha-induced IL-6 expression in airway smooth muscle by
      enhancing mRNA stability.
AB  - BACKGROUND: IL-17A is implicated in the regulation of inflammation and is found
      in increased amounts in the asthmatic airway. Human airway smooth muscle (ASM)
      cells synthesize cell adhesion molecules and cytokines in response to
      inflammatory mediators. OBJECTIVE: In this study, we examined whether IL-17A
      modulated the synthetic function of ASM cells. METHODS: Primary ASM cultures were
      treated with IL-17A alone and in combination with the proinflammatory cytokines
      TNF-alpha and IL-1beta. Intercellular adhesion molecule 1 expression, GM-CSF, and
      IL-6 secretion were measured by ELISA. Examination of transcriptional regulation
      was performed via transient transfection of promoter constructs, whereas mRNA
      stability was assessed by actinomycin D chase and quantitative real-time PCR.
      RESULTS: Airway smooth muscle did not secrete IL-17A after stimulation of ASM
      with TNF-alpha and IL-1beta. Furthermore, IL-17A (0.1-10 ng/mL) had no effect on
      TNF-alpha-induced and IL-1beta-induced intercellular adhesion molecule 1
      expression or GM-CSF secretion. However, IL-17A (10 ng/mL) significantly
      augmented TNF-alpha-induced IL-6 secretion 12-fold (TNF-alpha, 2.3 +/- 0.4 ng/mL;
      IL-17A and TNF-alpha, 27.5 +/- 4.8 ng/mL; P <.05) while having no effect on IL
      1beta-induced IL-6. Although IL-17A had no effect on nuclear factor kappaB
      mediated transcriptional regulation of IL-6 gene expression induced by TNF-alpha,
      IL-17A significantly augmented TNF-alpha-induced IL-6 mRNA stability. CONCLUSION:
      Collectively, these results demonstrate that IL-17A amplifies the synthetic
      function of ASM cells, acting via a posttranscriptional pathway, rather than
      transcriptional mechanisms, to augment TNF-alpha-induced secretion of IL-6 from
      ASM cells.

PMID- 15480344
TI  - Safety and efficacy of repeated monthly carboplatin desensitization.

PMID- 15480343
TI  - Cell-to-cell contact between activated CD4+ T lymphocytes and unprimed monocytes
      interferes with a TH1 response.
AB  - BACKGROUND: The production of IL-12 by monocytes and dendritic cells is tightly
      regulated and critically dependent on signals from surrounding cells in the
      micromilieu. OBJECTIVE: We studied the capacity of T cells to regulate directly
      the production of IL-12 by human monocytes. METHODS: Human isolated CD4 + T cells
      from peripheral blood and T cells from acute patch test lesions were cocultured
      with autologous monocytes. IL-12 expression and production were measured, and
      intracellular signal transduction pathways were studied. Monocytes, which had
      been cocultured with activated T cells, were further investigated for their
      capacity to induce TH1-directed responses. RESULTS: A marked inhibition of IL-12
      production was observable on coculture of monocytes with isolated CD4 + activated
      autologous T lymphocytes derived from blood or from acute eczematous skin
      lesions. The inhibiting effect of activated T lymphocytes on IL-12 production was
      dependent on cell-to-cell contact to monocytes but not on their ability to
      secrete soluble mediators. Experiments performed in the presence of mitogen
      activated protein kinase kinase 1/2 inhibitors provided evidence that activation
      of the p44/42 pathway plays an important role for the inhibition of IL-12
      production in monocytes (here referred to as IL-12 low monocytes). In addition, T
      cells cocultured with IL-12 low monocytes showed a markedly lower expression of
      the TH1 specific transcription factor T-bet, IFN-gamma, and IL-12Rbeta2 cell
      surface expression. CONCLUSION: Activated T lymphocytes may directly contribute
      to the TH2-like cytokine milieu found at sites of allergic inflammation (eg, in
      acute eczematous skin lesions) by inhibiting IL-12 production of unprimed antigen
      presenting cells.

PMID- 15480345
TI  - Recurrent anaphylaxis linked to pantoprazole.

PMID- 15480346
TI  - Alterations of stress-induced expression of membrane molecules and intracellular
      cytokine levels in patients with atopic dermatitis depend on serum IgE levels.

PMID- 15480347
TI  - Latex aeroallergen concentrations in ambulances.

PMID- 15480348
TI  - Anaphylaxis to mizolastine.

PMID- 15480349
TI  - Staphylococcus aureus colonization and IgE antibody formation to enterotoxins is
      increased in nasal polyposis.

PMID- 15480350
TI  - Treatment of infants coinfected with HIV-1 and cytomegalovirus with combination
      antiretrovirals and ganciclovir.

PMID- 15480351
TI  - Retrospective and prospective parental reports of sleep in children with asthma.

PMID- 15480352
TI  - Clinic record review of pediatric asthmatic patients after September 11, 2001,
      does not support authors' conclusions.

PMID- 15480353
TI  - Significance of the eudismic ratio and enantiomeric purity of the albuterol
      distomer.

PMID- 15480354
TI  - Lipoxins in asthma.

PMID- 15480356
TI  - Pediatric Chairs of Canada: academic pediatric workforce.

PMID- 15480357
TI  - The metabolic syndrome: antecedent of adult cardiovascular disease in pediatrics.

PMID- 15480358
TI  - Neurocognitive outcomes in sleep-disordered breathing.

PMID- 15480359
TI  - HHV6 and HHV7: persistence and vertical transmission.

PMID- 15480360
TI  - Demographic differences in congenital cytomegalovirus infection in the United
      States.

PMID- 15480361
TI  - Treatment of cystinosis: simple in principle, difficult in practice.

PMID- 15480363
TI  - Waist circumference percentiles in nationally representative samples of African
      American, European-American, and Mexican-American children and adolescents.
AB  - OBJECTIVE: To describe and provide estimates of the distribution of waist
      circumference (WC) according to percentiles in African-, European-, and Mexican
      American children, and to test for group differences at different percentiles.
      STUDY DESIGN: Cross-sectional data from the Third National Health and Nutrition
      Examination Survey (NHANES III) were examined. The sample evaluated included 9713
      nonpregnant persons 2 to 18 years of age with measured values of WCs. Age-, sex-,
      and ethnicity-specific percentiles were estimated via percentile regression.
      RESULTS: WC measurements increased in a monotonic fashion across ages but at
      nonconstant rates and in a manner that varied across age and sex. At higher
      percentiles of the distribution, estimates of WC differ between Mexican-American
      (MA) and European-American (EA) and between African-American (AA) and European
      American (EA), and, in some cases, exceeded the adult cutoff value for obesity
      related disease risk at as early as 13 years of age. CONCLUSION: Age-, sex-, and
      ethnicity-specific WC percentiles are available for US children and adolescents
      and can be used as an assessment tool that could impact public health
      recommendations. Results suggest concern with respect to high WC values among
      certain ethnic groups.

PMID- 15480365
TI  - Contrasting prevalence of and demographic disparities in the World Health
      Organization and National Cholesterol Education Program Adult Treatment Panel III
      definitions of metabolic syndrome among adolescents.
AB  - OBJECTIVE: To determine prevalence of metabolic syndrome (MS) among adolescents
      by using definitions from the National Cholesterol Education Program Adult
      Treatment Panel III (NCEP) and World Health Organization (WHO) guidelines and to
      compare the populations identified by these definitions. STUDY DESIGN: School
      based, cross-sectional study of 1513 black, white, and Hispanic teens who had a
      fasting morning blood sample drawn and a physical examination. RESULTS: Overall,
      the prevalence of NCEP-defined MS was 4.2% and of WHO-defined MS was 8.4%. MS was
      found almost exclusively among obese teens, for whom prevalence of NCEP-defined
      MS was 19.5% and prevalence of WHO-defined MS was 38.9%. Agreement between
      definitions was poor (kappa statistic=0.41). No race or sex differences were
      present for NCEP-defined MS. However, nonwhite teens were more likely to have MS
      by WHO criteria (RR, 1.40; 95% CI, 1.04, 1.87), and MS was more common among
      girls if the WHO-based definition was used (RR, 1.26; 95% CI, 1.08, 1.88).
      CONCLUSIONS: Among adolescents, obesity is a powerful risk for MS. Important
      demographic and clinical differences exist in the typology of MS, depending on
      the definition. Such discrepancies suggest that the concept of a common
      pathologic syndrome or etiologic mechanism underlying MS as defined by these
      guidelines may be flawed.

PMID- 15480366
TI  - Early onset of subclinical atherosclerosis in young persons with type 1 diabetes.
AB  - OBJECTIVE: To evaluate the degree of atherosclerosis and its risk factors in
      adolescents and young adults with type 1 diabetes. STUDY DESIGN: We measured
      carotid artery intima-media thickness (IMT) in 142 subjects with type 1 diabetes
      (mean [SD] age = 16.0 [2.6] years) and 87 control subjects (18.8 [3.1] years).
      Fasting lipid and homocysteine levels, degree of glycemic control, blood
      pressure, and body mass index were measured in persons with diabetes. RESULTS:
      The mean carotid IMT was greater in persons with diabetes ( P = .002). Among
      subjects with type 1 diabetes, lipid levels were significantly higher in female
      subjects compared with male subjects. The mean carotid IMT was significantly
      higher in persons with a diabetic complication (including hypertension,
      retinopathy, or microalbuminuria). In male subjects but not female subjects, HDL
      cholesterol and the LDL/HDL ratio were correlated with carotid IMT. CONCLUSIONS:
      Adolescents with type 1 diabetes have increased atherosclerosis compared with
      control subjects. Risk factors for increased carotid IMT in these younger
      patients include diabetic complications and HDL cholesterol and the LDL/HDL
      ratio, which may be sex-specific.

PMID- 15480367
TI  - Sleep-disordered breathing symptoms are associated with poorer cognitive function
      in 5-year-old children.
AB  - OBJECTIVE: To assess the relation of sleep-disordered breathing (SDB) symptoms in
      children to neurocognitive function. STUDY DESIGN: A cross-sectional, population
      based study of 205 5-year-old children. A parent-completed questionnaire was used
      to ascertain SDB symptoms, defined as frequent snoring, loud or noisy breathing
      during sleep, or witnessed sleep apnea. Polysomnography (PSG) data were available
      in 85% of children. Standardized neurocognitive tests were administered by a
      trained psychometrist unaware of the children's SDB status. Children with (n=61)
      and without SDB symptoms were compared using analysis of variance to adjust for
      demographic and respiratory health variables. RESULTS: Children with SDB symptoms
      scored significantly lower than those without SDB symptoms on tests of executive
      function (95.5 vs 99.9 on NEPSY Attention/Executive Core Domain, P=.02; 10.4 vs
      11.2 on Wechsler Preschool and Primary Scale of Intelligence, Revised [WPPSI-R]
      Animal Pegs test, P=.03), memory (96.8 vs 103.0 on NEPSY Memory Domain, P=.02),
      and general intellectual ability (105.9 vs 111.7 on WPPSI-R Full Scale IQ,
      P=.02). There were no significant differences on a computerized continuous
      performance task. These findings persisted when children with PSG evidence of
      obstructive sleep apnea (OSA) were excluded from analysis. CONCLUSION: Even in
      the absence of OSA, SDB symptoms are associated with poorer executive function
      and memory skills and lower general intelligence in 5-year-old children.

PMID- 15480368
TI  - Cardiorespiratory events detected by home memory monitoring and one-year
      neurodevelopmental outcome.
AB  - OBJECTIVE: To determine if infants with cardiorespiratory events detected by home
      memory monitoring during early infancy have decreased neurodevelopmental
      performance. STUDY DESIGN: Infants (n = 256) enrolled in the Collaborative Home
      Infant Monitoring Evaluation also completed the Bayley Scales of Infant
      Development II at 92 weeks' postconceptional age. Infants were classified as
      having 0, 1 to 4, or 5+ cardiorespiratory events. Events were defined as apnea
      >or=20 seconds or heart rate <60 to 80 bpm or <50 to 60 bpm, for >or=5 to 15
      seconds, depending on age. RESULTS: For term infants, having 0, 1 to 4, and 5+
      cardiorespiratory events was associated with unadjusted mean Mental Developmental
      Index (MDI) values (+/-SD) of 103.6 (10.6), 104.2 (10.7), and 97.7 (10.9),
      respectively, and mean Psychomotor Developmental Index (PDI) values of 109.5
      (16.6), 105.8 (16.5), and 100.2 (17.4). For preterm infants, having 0, 1 to 4,
      and 5+ cardiorespiratory events was associated with unadjusted mean MDI values of
      100.4 (10.3), 96.8 (11.5), and 95.8 (10.6), respectively, and mean PDI values of
      91.7 (19.2), 93.8 (15.5), and 94.4 (17.7). The adjusted difference in mean MDI
      scores with 5+ events compared with 0 events was 5.6 points lower in term infants
      ( P = .03) and 4.9 points lower in preterm infants ( P = .04). CONCLUSIONS:
      Having 5+ conventional events is associated with lower adjusted mean differences
      in MDI in term and preterm infants.

PMID- 15480369
TI  - Congenital infections with human herpesvirus 6 (HHV6) and human herpesvirus 7
      (HHV7).
AB  - OBJECTIVE: To examine whether: (1) congenital human herpesvirus 6 (HHV6) and
      human herpesvirus 7 (HHV7) infections occur; whether (2) their manifestations
      differ from postnatal infections; and whether (3) HHV6 and HHV7 infections differ
      despite their close relatedness. STUDY DESIGN: HHV6 and HHV7 infections acquired
      congenitally and postnatally in normal children were compared using viral
      isolation, serology, reverse-transcription polymerase chain reaction (RT-PCR) and
      nested DNA-PCR for HHV6 variant A (HHV6A), HHV6 variant B (HHV6B), and HHV7.
      RESULTS: HHV6 DNA was detected in 57 (1%) of 5638 cord bloods. HHV7 DNA, however,
      was not detected in 2129 cord bloods. Congenital HHV6 infections differed from
      postnatal infections, which were acute febrile illnesses. Congenital infections
      were asymptomatic, 10% demonstrated reactivation at birth, and HHV6 DNA
      persistence in follow-up blood samples was significantly more frequent. One-third
      of congenital infections were HHV6A, whereas all postnatal infections were HHV6B.
      CONCLUSIONS: Congenital HHV6 infections occurred in 1% of births, similar to the
      rate for cytomegalovirus infection. Congenital infections were clinically and
      virologically distinct from postnatal infections. Congenital HHV7 infections,
      however, were not detected, suggesting considerable differences in transmission
      and pathogenesis in these closely related beta-herpesviruses.

PMID- 15480370
TI  - Human herpesvirus 6 (HHV6) DNA persistence and reactivation in healthy children.
AB  - OBJECTIVE: To determine in healthy children after primary infection the
      persistence of human herpesvirus 6 (HHV6) DNA, the presence and frequency of HHV6
      re-activation or re-infection, and the relationship of both to illness and the
      presence of human herpesvirus 7 (HHV7) infection. STUDY DESIGN: Children 1 to 12
      years of age with previous HHV6 infection were prospectively evaluated by HHV6
      and HHV7 DNA polymerase chain reaction (PCR) and reverse transcription (RT)-PCR
      for HHV6. HHV6 plasma antibody titers were measured. Illnesses were recorded by
      diary, and physician records were reviewed. RESULTS: HHV6 DNA was detected in
      >or=1 peripheral blood mononuclear cell (PBMC) samples in 89% of children. HHV6
      reactivation and re-infection were detected by RT-PCR in 1.1% of samples.
      Detection of HHV6 DNA was intermittent in 76% of children and was not associated
      with cumulative rates of illness. Illness at a study visit was significantly
      associated with the absence of HHV6 and HHV7 DNA in PBMC samples and was not
      associated with HHV6 antibody titer or the presence of HHV6 DNA in saliva.
      CONCLUSIONS: HHV6 DNA persists in most children intermittently following primary
      infection and is unrelated to illness. Reactivation of HHV6 occurs in healthy
      children without apparent illness.

PMID- 15480372
TI  - Prevention of child-to-mother transmission of cytomegalovirus among pregnant
      women.
AB  - OBJECTIVE: To determine if protective behavior prevents child-to-mother
      transmission of cytomegalovirus (CMV) during pregnancy. STUDY DESIGN: We studied
      166 seronegative mothers (94% white women; mean age, 33 years) with a child <36
      months of age attending a day care facility. Mothers, either pregnant or
      attempting pregnancy, were randomly assigned by day care center to either a
      control or intervention group. Mothers in the intervention group received
      instructions for hand washing, glove use, and for avoiding types of intimate
      contact with their child. The control group received no instructions or
      information about their serologic status or whether their child was shedding CMV.
      RESULTS: In the intervention group, 7.8% of women (9 of 115) seroconverted, as
      did 7.8% of women (4 of 51) in the control group. Two independent predictors of
      maternal infection were (1) a child shedding and (2) a mother attempting
      pregnancy at enrollment. For 41 women attempting pregnancy at enrollment with a
      child shedding CMV, 10 of 24 became infected compared with only 1 of 17 women who
      were already pregnant at enrollment ( P = .008). CONCLUSIONS: For seronegative
      women who already know they are pregnant, intervention may be highly effective
      for preventing CMV acquisition.

PMID- 15480373
TI  - Delivery room decision-making at the threshold of viability.
AB  - OBJECTIVES: To assess attitudes of neonatologists toward parental wishes in
      delivery room resuscitation decisions at the threshold of viability. STUDY
      DESIGN: Cross-sectional survey of the 175 practicing level II/III neonatologists
      in six New England states. RESULTS: Response rate was 85% (149/175). At 24 1/7
      6/7 weeks' gestation, 41% of neonatologists considered treatment clearly
      beneficial, and at 25 1/7-6/7 weeks' gestation, 84% considered treatment clearly
      beneficial. When respondents consider treatment clearly beneficial, 91% reported
      that they would resuscitate in the delivery room despite parental requests to
      withhold. At or below 23 0/7 weeks' gestation, 93% of neonatologists considered
      treatment futile. Thirty-three percent reported that they would provide what they
      consider futile treatment at parental request. When respondents consider
      treatment to be of uncertain benefit, all reported that they would resuscitate
      when parents request it, 98% reported that they would resuscitate when parents
      are unsure, and 76% reported that they would follow parental requests to
      withhold. CONCLUSIONS: Variation in neonatologists' beliefs about the gestational
      age bounds of clearly beneficial treatment and attitudes toward parental wishes
      in the context of uncertainty is likely to impact the manner in which they
      discuss options with parents before delivery. This supports the importance of
      transparency in neonatal decision-making.

PMID- 15480374
TI  - Bradycardia and desaturation during skin-to-skin care: no relationship to
      hyperthermia.
AB  - OBJECTIVE: We recently found increased temperature and increased bradycardia and
      desaturation during skin-to-skin care (SSC). We wanted to determine if these
      effects were related. STUDY DESIGN: Twenty-two infants (median gestational age at
      birth 28.5 weeks [range 24-31], median age at study 25.5 days [range 10-60 days],
      median birth weight 1025 g [range 550-1525 g], median weight at study 1320 g
      [range 900-2460 g]) underwent three 2-hour recordings of breathing movements,
      nasal airflow, heart rate, and pulse oximeter saturation (SpO 2 ): at
      thermoneutrality (TN) during incubator care, at TN during SSC, and at elevated
      temperature (ET) during incubator care. Core temperature was measured via a
      rectal probe. Recordings were analyzed for the summed rate of bradycardia and
      desaturation (heart rate <2/3 of baseline; SpO 2 <or=80%). RESULTS: Rectal
      temperature remained unchanged during SSC and increased by 0.6 degrees C during
      ET ( P < .001). The summed rate of bradycardia and desaturation was increased
      during SSC but not during ET (TN: median 2.2/hour (range, 0-19), ET: median
      1.7/hour (range, 0-13), SSC: 3.0/hour (0-25), P < .02 SSC vs ET). CONCLUSION:
      Bradycardia and desaturation were increased during SSC, even at constant rectal
      temperature, whereas ET had no effect on these events. Moderate hyperthermia did
      not increase respiratory instability in preterm infants.

PMID- 15480375
TI  - Increased lung water and tissue damage in bronchopulmonary dysplasia.
AB  - OBJECTIVES: To test the hypothesis that high and asymmetrical water content
      persists in infants with bronchopulmonary dysplasia (BPD) and that this is
      associated with nonuniform lung damage. STUDY DESIGN: Magnetic resonance imaging
      was used to assess lung water content in 20 infants and tissue injury in 35
      infants of 23 to 33 weeks' gestational age (15 with severe BPD, 13 with mild BPD,
      and 7 without BPD). Relative proton density provided an index of water content
      and distribution. The location and extent of focal densities and cyst-like
      appearances indicating lung damage were defined. RESULTS: Proton density was
      significantly higher in dependent regions. Average proton density, proton density
      gradient, and severity of lung damage were greater in infants with severe BPD.
      Indicators of damage were greatest in dorsal lung regions. BPD was associated
      with a higher lung water burden and gravity-dependent atelectasis and/or alveolar
      flooding. Lesions were more common in dorsal lung regions in infants with severe
      lung damage. CONCLUSIONS: Infants with BPD have increased lung water and are
      susceptible to gravity-induced collapse and/or alveolar flooding in the dependent
      lung. Focal tissue damage appears to be distributed inhomogenously.

PMID- 15480376
TI  - Gastric emptying in very-low-birth-weight infants treated with nasal continuous
      positive airway pressure.
AB  - OBJECTIVE: Nasal continuous positive airway pressure (NCPAP) is frequently used
      for prolonged periods in very low birth weight infants. We asked if NCPAP affects
      gastric emptying. STUDY DESIGN: Preterm newborn infants (n = 16) with a mean body
      weight of 935 g (SD, 155) and a mean gestational age of 27.7 weeks (SD, 1.9) were
      treated with NCPAP and fed by orogastric tube. A comparison group of 20 newborn
      infants with a mean body weight of 1090 grams (SD, 130) and a mean gestational
      age of 28.2 weeks (SD, 1.2) were not receiving NCPAP. All newborn infants
      received a milk formula containing 81 kcal/dL given in similar quantities. The
      antral cross-sectional area was measured by means of an ultrasound technique.
      RESULTS: Mean half-time of antral cross-sectional area was 28 minutes (SD, 12) in
      the NCPAP group and 40 minutes (SD, 17) in the comparison group ( P < .05). There
      were no differences in gastrointestinal complications between the two groups.
      CONCLUSIONS: The gastric emptying time was shorter for newborn infants treated
      with NCPAP.

PMID- 15480377
TI  - Economic and psychologic costs for maternal caregivers of gastrostomy-dependent
      children.
AB  - OBJECTIVE: To examine the economic and psychologic costs of care provided by
      maternal caregivers to children with gastrostomy tube (GT) feedings. STUDY
      DESIGN: We conducted a 3-site study of primary maternal caregivers of 101
      chronically ill children, with (n = 50) and without (n = 51) enteral nutrition
      support by GT to determine the time spent providing technical care, nontechnical
      care, and health care management and to assess depressive mood and quality of
      life. Associated costs were determined. RESULTS: Caregivers spent 339.7 +/- 34.1
      (SEM) min/d to provide all care. Children with a GT required more than twice as
      much care time as children without a GT: 484.5 +/- 54.6 versus 197.8 +/- 30.6
      min/d ( P < .0001). The mean annual total value of home care by the primary
      caregiver for a child with a GT was 37,232 dollars, compared with 15,004 dollars
      for the child without a GT. Caregivers of children with GT were no more depressed
      or less satisfied with their lives than caregivers of children without GT.
      CONCLUSIONS: Use of a GT for enteral nutrition support is associated with
      significant increased care time by the primary caregiver but not at additional
      psychologic cost compared with caring for chronically ill children.

PMID- 15480378
TI  - Juvenile polyarteritis: results of a multicenter survey of 110 children.
AB  - OBJECTIVE: To characterize pediatric patients who had been diagnosed with
      polyarteritis nodosa (PAN) through necrotizing vasculitis of the small and mid
      size arteries or those with characteristic findings on angiograms data were
      collected. STUDY DESIGN: Pediatricians were asked to classify their patients into
      one of the four suggested groups for juvenile PAN. Twenty-one pediatric centers
      worldwide participated with 110 patients. RESULTS: The girl:boy ratio was 56:54,
      with a mean age of 9.05 +/- 3.57 years. The cases were classified as: 33 (30%)
      cutaneous PAN; 5 (4.6%) classic PAN associated with hepatitis B surface antigen
      (HBs Ag); 9 (8.1%) microscopic polyarteritis of adults associated with
      antineutrophil cytoplasmic antibodies (ANCA); and 63 (57.2%) systemic PAN.
      Cutaneous PAN was disease confined to the skin and musculoskeletal system. All
      patients with HBs Ag-associated classic PAN were diagnosed with renal angiograms.
      Antiviral treatment was administered in most cases. Microscopic PAN patients had
      pulmonary-renal disease, in combination or separately. ANCA was present in 87%,
      and 2 patients progressed to end-stage renal failure. Patients classified with
      systemic PAN had multiple system involvement, almost all had constitutional
      symptoms, and all had elevated acute phase reactants. Corticosteroids and
      cyclophosphamide were the first choices of immunosuppressive treatment. The
      overall mortality was 1.1%. CONCLUSIONS: There were remarkable differences among
      pediatric patients with PAN, with different clinical manifestations and overall
      better survival and lower relapse rates when compared with adults.

PMID- 15480379
TI  - Emotional quality-of-life and outcomes in adolescents with asthma.
AB  - OBJECTIVE: Examine the association between emotional quality-of-life (QOL) and
      asthma morbidity in adolescents with asthma. STUDY DESIGN: Cross-sectional survey
      of 185 adolescents with asthma 11 to 17 years of age cared for in three managed
      care organizations (MCOs) in the United States. The asthma-specific Pediatric
      Asthma Quality of Life Questionnaire (PAQLQ) and a short version of the generic
      Child Health and Illness Profile-Adolescent Edition (CHIP-AE) were used to assess
      emotional QOL. Asthma morbidity measures were: asthma control, emergency
      department (ED) visits, hospitalizations, doctor visits for worsening asthma, and
      missed school because of asthma. RESULTS: Of the adolescents surveyed, 45%
      reported feeling depressed, 41% had ED visits, and 30% missed >or=1 day of school
      because of asthma. Poorer asthma-specific emotional QOL was associated with
      poorer control of asthma symptoms ( P < .0001), missed school (OR 7.1, P < .05),
      and doctor visits for worsened asthma (OR = 7.0, P < .05). CONCLUSIONS: Emotional
      symptoms related to asthma are common in adolescents with persistent asthma and
      asthma-specific QOL is related to increased asthma morbidity, healthcare use, and
      school absenteeism. Adolescents with high morbidity from asthma exhibit poorer
      QOL. Therefore, the evaluation of asthma-specific emotional QOL should be
      included in the assessment of adolescents with asthma.

PMID- 15480380
TI  - Incidence of Smith-Lemli-Opitz syndrome in Canada: results of three-year
      population surveillance.
AB  - OBJECTIVES: To determine the incidence and point prevalence of Smith-Lemli-Opitz
      syndrome (SLOS) in Canada; to determine the percentage of mild cases of SLOS; and
      to determine the age of diagnosis of mildly affected patients. SLOS is a
      treatable genetic condition that may be difficult to diagnose in its mildest form
      because of nonspecific clinical markers (two- to three-toe webbing, short
      upturned nose, and micrognathia). STUDY DESIGN: More than 2000 Canadian
      pediatricians and pediatric specialists were surveyed monthly for 36 months
      through a standing national surveillance program. A clinical identification form
      was designed to identify patients with SLOS or its phenocopies. Clinical
      information was obtained on all reported cases; suggested cases were investigated
      by biochemical or molecular analysis. RESULTS: Thirty-five of 86 reports of
      suggested SLOS were confirmed SLOS. Twelve infants with SLOS were born during the
      surveillance period, and two additional infants with SLOS were diagnosed
      prenatally. Twenty-one infants with SLOS were born before the onset of
      surveillance. CONCLUSIONS: The minimum incidence of SLOS in Canada is 1 in 70,358
      live births. The minimum prevalence of SLOS is approximately 1 in 950,000.
      Eighteen percent of patients were mildly affected; the mean age of diagnosis of
      mildly affected patients was 5.3 years.

PMID- 15480381
TI  - Optic nerve size evaluated by magnetic resonance imaging in children with optic
      nerve hypoplasia, multiple pituitary hormone deficiency, isolated growth hormone
      deficiency, and idiopathic short stature.
AB  - OBJECTIVE: To objectively define criteria for intracranial optic nerve (ON) size
      in ON hypoplasia (ONH) on magnetic resonance imaging (MRI) scans. STUDY DESIGN:
      Intracranial ON sizes from MRI were compared between 46 children with ONH
      diagnosed by ophthalmoscopy (group 1, isolated ONH, 8 children; and group 2, ONH
      associated with abnormalities of the hypothalamic-pituitary axis and septum
      pellucidum, 38 children) and children with multiple pituitary hormone deficiency
      (group 3, multiple pituitary hormone deficiency, 14 children), isolated growth
      hormone deficiency (group 4, isolated growth hormone deficiency, 15 children),
      and idiopathic short stature (group 5, idiopathic short stature, 10 children).
      Intracranial ON size was determined by the cross-sectional area, calculated as
      [pi x (1/2) height x (1/2) width]. RESULTS: Groups 1 and 2 had lower intracranial
      ON size than did groups 3, 4, and 5 (P < .001). No patients in groups 3 through 5
      who had MRI after 12 months of age (when 95% adult size of ONs is attained) had
      ONs <2.9 mm 2 . Visual acuity correlated significantly with ON size (P < .01).
      CONCLUSIONS: Magnetic resonance imaging of the ONs with cross-sectional area <2.9
      mm 2 in a short child more than 12 months of age, with or without hypothalamic
      pituitary axis abnormalities, confirms the clinical diagnosis of ONH.

PMID- 15480382
TI  - Growth hormone in T-lymphocyte thymic and postthymic development: a study in HIV
      infected children.
AB  - OBJECTIVES: Growth hormone (GH) plays a role in thymic function, and recombinant
      GH may stimulate thymopoiesis in HIV-infected individuals. We performed
      immunologic analyses in 26 antiretroviral-treated children matched for age,
      pubertal status, clinical parameters, and antiretroviral exposure who did or did
      not show an impaired response to GH-release stimulation tests with arginine + GH
      releasing hormone. RESULTS: The following abnormalities were found in GH
      deficient compared with GH-nondeficient children after >4 years of therapy: CD4
      count ( P = .02) and percentage ( P = .03), CD4 as percentage of normal cells for
      age ( P = .003), serum interleukin-7 concentration ( P = .02), and thymic volume
      ( P = .01). Naive CD4 (4+62+RA+ and 4+CCR7+RA+) and CD8 (8+CCR7+RA+) lymphocytes
      were lower in GH-deficient children ( P = .003; P = .007; and P = .02,
      respectively). Postthymic pathways were also impaired in GH-deficient children.
      Thus, central memory (4+CCR7+RA-) CD4+ cells were reduced ( P = .006), whereas
      effector memory (4+CCR7-RA-) CD4+ cells ( P = .002) and late effector CD8+
      lymphocytes (8+CCR7-RA+ and 8+27-28-) ( P = .009 and P = .002, respectively) were
      increased in these children. CONCLUSIONS: Growth hormone plays a role in thymic
      and postthymic pathways, and defective GH production may be associated with
      incomplete immunoreconstitution. Immunomodulant agents (including GH) could be
      useful in patients with defective GH production.

PMID- 15480383
TI  - Growth hormone deficiency in HIV-infected children following successful treatment
      with highly active antiretroviral therapy.
AB  - Growth failure is common in children with untreated HIV, although growth hormone
      (GH) deficiency is rare. Treatment with highly active antiretroviral therapy
      usually results in resumption of normal growth. We report the cases of 2 children
      with growth failure despite stable full suppression of viremia who were found to
      be GH deficient.

PMID- 15480384
TI  - Restoration of ureagenesis in N-acetylglutamate synthase deficiency by N
      carbamylglutamate.
AB  - In a patient with N-acetylglutamate synthase (NAGS) deficiency, incorporation of
      an isotopic label from ammonium chloride into urea was markedly reduced before
      treatment with N-carbamyl-L-glutamate (NCLG) and completely normalized following
      treatment. Blood ammonia rose following ammonium tracer ingestion before
      treatment but remained low following treatment. Serum urea concentration doubled
      following the treatment.

PMID- 15480385
TI  - Long-term follow-up of well-treated nephropathic cystinosis patients.
AB  - We report the excellent clinical outcomes of siblings with nephropathic
      cystinosis treated diligently with cysteamine starting at 20 months and 2 months
      of age. Now 15 and 8 years old, they have glomerular filtration rates of 78 and
      105 mL/min/1.73m 2 , respectively. These cases illustrate the critical importance
      of early diagnosis and treatment.

PMID- 15480386
TI  - Fatal cerebral infarctions in diabetic ketoacidosis in a child with previously
      unknown heterozygosity for factor V Leiden deficiency.
AB  - An 11-year-old boy with poorly controlled diabetes had sudden collapse after the
      development of lower extremity deep venous thrombosis, with fatal cerebral
      infarctions. He was heterozygous for factor V Leiden deficiency. This case
      emphasizes the value of cranial imaging after initial resuscitative treatment of
      neurologic collapse in diabetic ketoacidosis.

PMID- 15480387
TI  - Incidence of venous thromboembolism in infants and children: data from the
      National Hospital Discharge Survey.
AB  - Pulmonary embolism (PE), deep venous thrombosis (DVT), and the combination were
      not rare in pediatric patients in the United States from 1979 to 2001. They were
      more frequent in infants 0 to 1 year of age and in teenagers 15 to 17 years of
      age than in children 2 to 14 years of age. Pregnancies doubled the rate of DVT in
      teenage girls.

PMID- 15480388
TI  - Fluoroscopic-guided balloon dilation of tracheal stenosis in a 26-week premature
      infant.

PMID- 15480389
TI  - A molecular diagnosis of hyperparathyroidism-jaw tumor syndrome in an adolescent
      with recurrent kidney stones.

PMID- 15480391
TI  - Valuing childhood vaccines.

PMID- 15480393
TI  - Nebulized sodium nitroprusside.

PMID- 15480400
TI  - Blinded by the broken mirror.

PMID- 15480401
TI  - Analysis of screw pullout strength: a function of screw orientation in subtalar
      joint arthrodesis.
AB  - The purpose of this cadaveric study was to compare the pullout strength and
      failure load of 2 different screw orientations for subtalar arthrodesis. Twenty
      six specimens from 13 cadaver donors (1 left and 1 right each) were used. A 7.3-
      x 65-mm long-thread profile (32-mm length) cannulated screw inserted into the
      calcaneus from dorsal to plantar (calcaneal specimens) was compared with a 7.3- x
      65-mm short-thread profile (16-mm length) cannulated screw inserted into the
      talus from plantar to dorsal (talar specimens). A torque screwdriver with a
      calibrated electronic vernier scale measured the torque of screw insertion. Screw
      pullout strength and load failure were measured by using a servohydraulic
      materials testing machine. Distraction was applied along the axis of the screw at
      a displacement rate of 25 mm/min. The peak torque of insertion in all calcaneal
      specimens was reached on initial insertion through the dorsal subchondral bone
      plate of the calcaneus; in talar specimens, it was reached as the screw threads
      were completely buried into the talus. A significant difference (P = .00647) was
      found between the mean torque of insertion for the calcaneal (1.50 Nm) and talar
      specimens (1.30 Nm). A comparison of pullout forces showed a significantly
      stronger mean failure load for calcaneal specimens (P = .000085). The mean
      failure load for paired calcaneal specimens was 1782 N compared with a mean 1245
      N for talar specimens. Although the pullout force was clearly greater in the
      dorsal-to-plantar screw application, the pullout force in the plantar-to-dorsal
      orientation was also considerable.

PMID- 15480402
TI  - Bisphosphonates for the treatment of Charcot neuroarthropathy.
AB  - Excess osteoclastic activity is believed to be responsible for the destruction in
      Charcot neuropathic joint disease. By intervening early in the destructive
      process, it may be possible to halt the progression toward the devastating bone
      and joint deformity responsible for morbidity in Charcot feet. This retrospective
      study evaluated the effects of the bisphosphonate pamidronate on associated signs
      of Charcot. The 13 study patients (14 infusions) administered pamidronate were
      compared with 10 control patients who were treated with traditional
      immobilization methods. Limb temperature and alkaline phosphatase levels were
      measured as markers of the Charcot process. After pamidronate infusion, limb
      temperature decreased a mean 2.8 degrees F by 48 hours and 7.4 degrees F by 2
      weeks. The alkaline phosphatase levels also decreased an average 53% 2 weeks
      after infusion. The control group showed no reduction in limb temperature at 48
      hours, and had an average limb temperature reduction of 2.3 degrees F at 2 to 3
      weeks. This was significantly less than the temperature reduction in the treated
      group ( P = .008 at 48 hours and P = .001 at 2 weeks). Mean alkaline phosphatase
      levels declined only 9% in the control group, a significantly smaller decline
      than in the pamidronate-infusion group ( P = .001). These results suggest that
      pamidronate may be useful in halting the acute phase of Charcot neuroarthropathy.

PMID- 15480403
TI  - Lapidus arthrodesis for management of hallux valgus--a retrospective review of
      106 cases.
AB  - One hundred six patients who underwent a Lapidus arthrodesis for a symptomatic
      hallux valgus deformity, mainly with first ray hypermobility, were
      retrospectively reviewed. Radiograph and chart reviews were performed in addition
      to a patient survey completed at a mean 17 months postoperatively. Of the 78
      patients who completed the survey, 70.5% were satisfied with the procedure; 80.2%
      would choose the same method again. Seven percent of patients were dissatisfied.
      Review of preoperative and 3-month postoperative radiographs showed a mean
      intermetatarsal angle reduction of 12.4 degrees . The average postoperative
      sesamoid position was 2.5, a 4.0 reduction from the preoperative mean value of
      6.5. The complication rate was 5.7%, including 2 nonunions (1.8%) requiring a
      repeat surgery, 1 deep-vein thrombosis (0.9%), and 3 patients with complex
      regional-pain syndrome (2.7%). In 16% of patients, resolution of swelling and
      subjective complaints took longer than 3 months; 4.7% of patients developed
      sesamoiditis or metatarsalgia that resolved with conservative measures.
      Radiographic undercorrection was evident in 4.7% of patients. The results showed
      that the Lapidus procedure provided reliable correction in cases of severe hallux
      valgus with intermetatarsal angles >15 degrees and in those patients with first
      ray hypermobility.

PMID- 15480404
TI  - Characteristic trends of lower-extremity complex regional pain syndrome.
AB  - Complex regional pain syndrome (CRPS) is a multifaceted, progressive, and
      potentially devastating disorder generally affecting the extremities. In
      addition, scant information is available regarding the types of patients who
      develop lower-extremity CRPS. This is a retrospective chart review study of 64
      patients who presented to a pain clinic with CRPS of the lower extremity. The
      study examined 23 variables broadly classified under demographic characteristics,
      CRPS characteristics, and healthcare utilization. The sample was found to consist
      of predominantly white, middle-aged women with CRPS I. Subjective complaints
      consisted of burning, sharp, throbbing, or aching pain with shooting symptoms.
      Initial presenting clinical findings included allodynia, edema, erythema, and
      hyperesthesia. The most common precipitating injuries were blunt trauma of the
      foot with or without fracture or ankle sprain. The most common inciting surgical
      events were bunionectomy, tarsal tunnel release, and heel-spur surgery. Referral
      to the pain clinic was delayed more commonly in trauma patients than in
      postsurgical patients, with a corresponding increase in pain clinic visits for
      treatment. This study may act as a guide for physicians treating the lower
      extremity to aid in the recognition of lower extremity complex regional pain
      syndrome and its characteristics.

PMID- 15480405
TI  - Endoscopic gastrocnemius recession: preliminary report on 18 cases.
AB  - A technique of endoscopic gastrocnemius recession was evaluated. Fifteen patients
      undergoing 18 procedures were prospectively studied with a minimum follow-up of 1
      year. There were 9 women and 6 men (mean age, 44.1 +/- 22.6 years). One patient
      had an isolated recession; the others had various adjunctive flatfoot or
      reconstructive procedures. Pre- and postoperative ankle dorsiflexion was
      evaluated, as was the amount of time before patients could perform a single-leg
      heel raise postoperatively. The mean preoperative ankle dorsiflexion with the
      knee extended was -8.7 degrees +/- 3.5 degrees , which improved from a mean 14.9
      degrees at 3 months postoperatively to a mean 6.2 degrees +/- 2.6 degrees . At 12
      months postoperatively, this value was 3.6 degrees +/- 1.8 degrees , a net
      postoperative improvement of 12.6 degrees (P < .00001). Patients were able to
      perform a single-leg heel raise on an average of 13.0 +/- 6.0 weeks.
      Complications were mostly related to lateral foot dysesthesia in the distribution
      of the sural nerve (N = 3). Furrowing of the medial leg was noted in 1 patient.
      No hematomas or neuromas associated with the portal sites were found. These
      results show endoscopic gastrocnemius recession to be an acceptable method of
      lengthening the gastrocnemius complex.

PMID- 15480406
TI  - Use of a simple suture to stabilize the chevron osteotomy: a prospective study.
AB  - A clinical and radiographic review was undertaken in 27 patients (30 feet) who
      underwent a chevron osteotomy stabilized with a double loop of polydioxanone
      suture. The mean patient age at the time of surgery was 40 years (range, 16 to 66
      years). At 6 weeks postoperatively, all patients showed clinical and radiographic
      union at the osteotomy site. In 1 foot, the initial correction was lost with
      radiographic evidence of an angulated distal fragment with no medial translation.
      There were no cases of wound infection, sinus formation, or avascular necrosis of
      the metatarsal head. No patients required further surgery. This method of
      stabilizing a chevron osteotomy is technically straight forward, with a
      predictable outcome, and provides a valid low cost alternative to screw,
      bioabsorbable implant, or Kirschner wire.

PMID- 15480407
TI  - First metatarsophalangeal joint arthrodesis: a new technique of internal fixation
      by using memory compression staples.
AB  - A prospective clinical study of first metatarsophalangeal joint arthrodesis using
      memory compression staples is presented. In 27 patients, 30 feet underwent
      surgery. There were 24 women and 3 men, with a mean age of 61.2 years. Two memory
      compression staples were used at right angles to each other to achieve
      compression at the fusion site. Postoperatively, patients were allowed full
      weightbearing in a rigid-soled shoe. Subjective assessment was performed with a
      standard questionnaire, which included questions regarding level of pain,
      ambulation, and patient satisfaction. Objective assessment was performed by a
      clinical and included a radiographic examination. There was a postoperative
      reduction in the pain score from 4.6 to 1.6 (P < .0001). Ambulation ability
      improved from 4 to 2.5 (P < .0001). Patients reported 86.6% excellent to good
      results, and 96.7% achieved radiographic fusion at an average 8.2 weeks. The only
      significant postoperative complication was a single nonunion. The authors
      advocate memory compression staples for the internal fixation of first
      metatarsophalangeal joint arthrodesis. The implant is low profile, and
      postoperative cast immobilization is not required. The use of this device has a
      predictable success rate comparable to previously reported methods.

PMID- 15480408
TI  - Pseudoaneurysm after modified Lapidus arthrodesis: a case report.
AB  - Pseudoaneurysms are a pulsatile swelling secondary to an arterial-wall defect.
      Blood flows through the defect but is contained within the surrounding soft
      tissue. This article describes a rare form of an iatrogenic pseudoaneurysm of the
      perforating deep plantar artery 1 month after a modified Lapidus arthrodesis for
      hallux valgus. A presumptive diagnosis of pseudoaneurysm was confirmed by Doppler
      ultrasonography. The patient was treated with ligation of the artery and
      resection of the pseudoaneurysm and remained free of symptoms 1 year
      postoperatively.

PMID- 15480409
TI  - Total extrusion of the talus: a case report.
AB  - Total extrusion of the talus without recovery of the bone is a very unusual
      injury. The authors present a case of a 25-year-old man who sustained an open
      total enucleation of the talus in a motorcycle accident. The talus was not
      recovered at the scene of the accident. An immediate tibiocalcaneal stabilization
      was performed by using an external fixator. In the postoperative period, a
      polymicrobic infection was observed and treated with parenteral antibiotics. Nine
      months after injury, the patient developed an infection of both the empty space
      and the distal third of the tibia. A wound debridement with tibial sequestrectomy
      and insertion of gentamicin-impregnated polymethylmethacrylate beads was
      performed. Three months later, after multiple negative bacteriologic
      examinations, a tibiocalcaneal arthrodesis with staples and autogenous bone graft
      was performed. Because of a pseudoarthrosis, the patient underwent a revision of
      the arthrodesis by retrograde tibiocalcaneal nailing, achieving clinical and
      radiographic success. The definitive treatment of total enucleation of the talus
      is still controversial because of its rarity and the high rate of complications,
      such as avascular necrosis, osteomyelitis, and ankle stiffness. In this case,
      without recovery of the talus, retrograde nailing afforded good stability by
      bypassing the bone defects.

PMID- 15480410
TI  - Madura foot: atypical finding and case presentation.
AB  - Mycetomas are chronic, subcutaneous infections characterized by a clinical triad
      of chronic induration, draining sinuses, and discharge of granules. The granules
      are composed of colonies of either actinomycotic bacteria or eumycotic fungi. The
      infection develops after traumatic inoculation with contaminated soil and
      progresses to adjacent tissues or bone. The foot, hand, and lower-leg regions are
      the most commonly affected areas. Treatment can be difficult and includes
      surgical debridement with prolonged antibiotic or antifungal treatment. Mycetomas
      are primarily found in tropical and subtropical areas of the world and are
      relatively rare in the United States. A case of indigenously obtained
      actinomycoses that was successfully treated with surgical resection and long-term
      antibiotic therapy is presented. This case is unique because of the rarity of
      contracting this type of infection in the United States. Mycetomas have been
      reported in southern states, but there are no reported cases of obtaining this
      pathogen in Michigan. This case stresses the need for clinical suspicion of this
      rare dermatosis, especially considering the increase in immigration to the United
      States.

PMID- 15480411
TI  - Posterior calcaneal displacement osteotomy: a new percutaneous technique.

PMID- 15480412
TI  - Percutaneous displacement calcaneal osteotomy.

PMID- 15480413
TI  - Strand invasion involving short tract gene conversion is specifically suppressed
      in BRCA2-deficient hamster cells.
AB  - The BRCA2 tumour suppressor protein is involved in maintaining genetic stability
      through its role in homologous recombination (HR), where it mediates RAD51
      dependent strand invasion. Here, we show that BRCA2-defective cells are not
      completely impaired in HR by strand invasion although the spontaneous HR rate is
      10-fold lower than that in wild-type cells. Furthermore, a DNA double-strand
      break (DSB) triggers HR repair by strand invasion also in BRCA2-defective cells,
      but less efficiently. Thus, either the strand invasion pathway(s) in which BRCA2
      operates is still operative in the absence of a functional BRCA2, albeit at a
      reduced frequency, or there is a separate pathway for strand invasion still
      functional in BRCA2-deficient cells. Consistent with the latter hypothesis, we
      show that HR events occurring in BRCA2-defective cells differ from HR events in
      wild-type cells. These data suggest that BRCA2-defective hamster cells are
      impaired in short tract gene conversion but maintain proficiency in sister
      chromatid exchange.

PMID- 15480414
TI  - Blockage of CRM1-dependent nuclear export of the adenovirus type 5 early region
      1B 55-kDa protein augments oncogenic transformation of primary rat cells.
AB  - The 55-kDa gene product from subgroup C adenovirus type 5 (Ad5) early region 1
      (E1B-55kDa) plays a central role in the oncogenic transformation of primary
      rodent cells primarily by inactivating transcriptional and presumably other
      functional properties of the tumor suppressor protein p53. We have previously
      shown that Ad5 E1B-55kDa possesses a leucine-rich nuclear export signal (NES),
      which confers rapid nucleocytoplasmic shuttling via the CRM1-dependent export
      pathway. In this study we report that an export-deficient mutant of the viral
      protein (E1B-NES) substantially enhances focus formation of primary baby rat
      kidney cells in combination with Ad E1A. Transformed rat cells stably expressing
      the E1B-NES protein exhibited increased tumorigenicity and accelerated tumor
      growth in nude mice compared to transformants containing the wild-type E1B
      product. This 'gain of function' correlated with enhanced inhibition of p53
      transactivation in transient reporter assays and the accumulation of the mutant
      protein and p53 in several dot-like subnuclear aggregates. Interestingly, these
      structures also contained a large fraction of cellular promyelocytic leukemia
      protein (PML), a known regulator of p53. These data indicate that E1B-NES
      promotes oncogenic transformation by combinatorial mechanisms that involve
      modulation of p53 in the context of PML nuclear bodies. In sum, these results
      extend our previous observation that inhibition of PML activities by E1B-55kDa is
      required for efficient focus formation and provide further support for the view
      that blocking p53 transcriptional functions is the principal mechanism by which
      the Ad protein contributes to complete cell transformation in conjunction with Ad
      E1A.

PMID- 15480415
TI  - Protein kinase A isozyme switching: eliciting differential cAMP signaling and
      tumor reversion.
AB  - The cAMP-dependent protein kinase types I (PKA-I) and II (PKA-II), composed of
      identical catalytic (C) subunits but distinct regulatory (R) subunits (RI versus
      RII), are expressed in a balance of cell growth and differentiation. Distortion
      of this balance may underlie tumorigenesis and tumor growth. Here, we used PC3M
      prostate carcinoma cells as a model to overexpress wild type and mutant R and C
      subunit genes and examined the effects of differential expression of these genes
      on tumor growth. Only the RIIbeta and mutant RIalpha-P (a functional mimic of
      RIIbeta) transfectants exhibited growth inhibition in vitro, reverted phenotype,
      and apoptosis, and inhibited in vivo tumor growth. DNA microarrays demonstrated
      that RIIbeta and RIalpha-P overexpression upregulated a cluster of
      differentiation genes, while downregulating transformation and proliferation
      signatures. Overexpression of RIalpha and Calpha, which upregulated PKA-I,
      elicited the expression signatures opposite that elicited by RIIbeta
      overexpression. Total colocalization of Calpha and RIIbeta seen by confocal
      microscopy in the RIIbeta cell nucleus supports the opposed genomic regulation
      demonstrated between Calpha and RIIbeta cells. Differential expression of PKA R
      subunits may therefore serve as a tumor-target-based gene therapy for PC3M
      prostate and other cancers.

PMID- 15480416
TI  - Increased expression of Drosophila tetraspanin, Tsp68C, suppresses the abnormal
      proliferation of ytr-deficient and Ras/Raf-activated hemocytes.
AB  - Tetraspanins are evolutionary conserved transmembrane proteins thought to
      facilitate cell proliferation, movement or fusion by acting as organizers of
      different signaling events. Despite their prevalence and conservation, their
      specific role and functions remain largely elusive, as their redundancy in
      various organisms has hindered loss of function studies. Here, we take a gain of
      function approach to study Drosophila tetraspanin Tsp68C and its effect on larval
      hemocytes. We recently characterized a lethal mutation in ytr, a conserved gene
      that encodes a nuclear arginine-rich protein of unknown function, which is
      accompanied by abnormal differentiation and proliferation of the larval
      hematopoietic tissue in flies. A hemolectin (hml)-Gal4 construct carried by hml
      Gal4 transgenic flies was sufficient by itself to abrogate the hematopoietic
      defects in ytr mutant larvae. This rescue correlated with the overexpression of
      tsp68C, a tetraspanin gene nested in the hml promoter. The suppression of
      abnormal proliferation by the hml-Gal4 construct was not restricted to ytr
      deficient hemocytes, but was also observed in hemocytes expressing the oncogenic
      forms of Raf or Ras proteins. However, it had no effect on overproliferation
      mediated by a constitutively active form of Jak. New hml-Gal4 lines, in which the
      tsp68C gene was silenced or deleted from the promoter, no longer rescued the
      hematopoietic defect in ytr mutants nor suppressed the activated Raf-induced
      overproliferation. Therefore, change in tetraspanin Tsp68C expression has a
      strong suppressor effect on abnormal proliferation and differentiation of
      hemocytes in the context of specific lesions, such as overactivation of the
      Ras/Raf/MAPK pathway.

PMID- 15480417
TI  - Cre-loxP-controlled periodic Aurora-A overexpression induces mitotic
      abnormalities and hyperplasia in mammary glands of mouse models.
AB  - Aurora-A, a serine/threonine mitotic kinase, was reported to be overexpressed in
      various human cancers, and its overexpression induces aneuploidy, centrosome
      amplification and tumorigenic transformation in cultured human and rodent cells.
      However, the underlying mechanisms and pathological settings by which Aurora-A
      promotes tumorigenesis are largely unknown. Here, we created a transgenic mouse
      model to investigate the involvement of Aurora-A overexpression in the
      development of mammary glands and tumorigenesis using a Cre-loxP system. The
      conditional expression of Aurora-A resulted in significantly increased
      binucleated cell formation and apoptosis in the mammary epithelium. The surviving
      mammary epithelial cells composed hyperplastic areas after a short latency.
      Induction of Aurora-A overexpression in mouse embryonic fibroblasts prepared from
      the transgenic mice also led to aberrant mitosis and binucleated cell formation
      followed by apoptosis. The levels of p53 protein were remarkably increased in
      these Aurora-A-overexpressing cells, and the apoptosis was significantly
      suppressed by deletion of p53. Given that no malignant tumor formation was found
      in the Aurora-A-overexpressing mouse model after a long latency, additional
      factors, such as p53 inactivation, are required for the tumorigenesis of Aurora-A
      overexpressing mammary epithelium. Our findings indicated that this mouse model
      is a useful system to study the physiological roles of Aurora-A and the genetic
      pathways of Aurora-A-induced carcinogenesis.

PMID- 15480418
TI  - Mlh1 mediates tissue-specific regulation of mitotic recombination.
AB  - Mitotic recombination (MR) between chromosome homologs in somatic cells is a
      major pathway to the loss of heterozygosity (LOH), which may cause cancer if
      tumor suppressor genes are involved. MR can be suppressed by DNA sequence
      heterology (homeology) in hybrid mice from matings between species or between
      subspecies. We now report that MR is relatively suppressed in F1 hybrids between
      inbred strains C57BL/6 and 129S2. The frequency of MR in fibroblasts is lower in
      F1 hybrid mice than in either of the two parental strains. However, MR in T cells
      is not affected by strain background. Thus, relatively small genetic differences
      are capable of restricting MR in a tissue-specific manner. Using Mlh1-deficient
      mice, we tested the role of mismatch repair in MR in two isogenic cell types. In
      fibroblasts of C57BL/6 x 129S2 F1 mice, the suppression of MR is alleviated in
      the absence of MLH1. In contrast, MR is not affected by Mlh1 status in T cells.
      The frequency of point mutations at the reporter gene loci Aprt and Hprt, on the
      other hand, is significantly increased in both T cells and fibroblasts of Mlh1(-/
      ) mice. Thus, different cell types respond differently to MLH1 deficiency, and
      the contribution of MR to tumorigenesis may be tissue-dependent in the absence of
      mismatch repair.

PMID- 15480419
TI  - PPARdelta status and Apc-mediated tumourigenesis in the mouse intestine.
AB  - Based on recent reports that peroxisome proliferator-activated receptor delta
      (PPARdelta) activation promotes tumourigenesis, we have investigated the role of
      this protein in Apc-mediated intestinal tumourigenesis. We demonstrate that the
      inactivation of Apc in the adult small intestine, while causing the expected
      nuclear accumulation of beta-catenin, does not cause the expected increase in
      PPARdelta mRNA or protein but conversely, the levels of PPARdelta mRNA and
      protein are lowered. Furthermore, we find that ApcMinPPARdelta-null mice exhibit
      an increased predisposition to intestinal tumourigenesis. Our data suggest that
      PPARdelta is not directly regulated by beta-catenin, and that inhibition of
      PPARdelta activity is unlikely to be an appropriate strategy for the
      chemoprevention or chemotherapy of intestinal malignancies.

PMID- 15480420
TI  - The erythropoietin-receptor pathway modulates survival of cancer cells.
AB  - Anemia in cancer patients is associated with reduced quality of life and local
      failure after radiation treatment. However, the use of erythropoietin to correct
      cancer anemia and to improve radiation efficacy was disappointing. Erythropoietin
      receptor signaling mainly acts via activation of STAT 5, but also crossactivates
      the antiapoptotic transcription factor NF-kappaB. This causes neuroprotection
      against oxidative stress and implies radioprotection. In order to investigate
      possible radioprotective effects of erythropoietin-receptor signaling, we used an
      in vitro model system employing HeLa TetOff cells, stably transfected with an
      expression vector for the erythropoietin-receptor gene. Using electrophoretic
      mobility shift assays, we could demonstrate strong activation of NF-kappaB by
      erythropoietin-receptor signaling in HeLa cells. Activation of NF-kappaB did not
      require degradation of IkappaBalpha and was not prevented by proteasome
      inhibition. Furthermore, stimulation with erythropoietin resulted in a 50%
      increased clonogenicity of erythropoietin-receptor-expressing cells but did not
      alter radiation sensitivity itself. As most human tumors express erythropoietin
      receptor, we advocate a restricted use erythropoietin to patients suffering from
      erythropoietin-receptor-expressing cancers.

PMID- 15480421
TI  - Distinctive pattern of LINE-1 methylation level in normal tissues and the
      association with carcinogenesis.
AB  - Genome-wide losses of DNA methylation have been regarded as a common epigenetic
      event in malignancies and may play crucial roles in carcinogenesis. Limited
      information is available on the global methylation status in normal tissues and
      other cancer types beyond colonic carcinoma. Here we applied the combined
      bisulfite restriction analysis PCR to evaluate the methylation status of LINE-1
      repetitive sequences in genomic DNA derived from microdissected samples from
      several human normal and neoplastic tissues. We found that methylation of LINE-1
      in leukocytes was independent of age and gender. In contrast, normal tissues from
      different organs showed tissue-specific levels of methylated LINE-1. Globally,
      most carcinomas including breast, colon, lung, head and neck, bladder, esophagus,
      liver, prostate, and stomach, revealed a greater percentage of hypomethylation
      than their normal tissue counterparts. Furthermore, DNA derived from sera of
      patients with carcinoma displayed more LINE-1 hypomethylation than those of
      noncarcinoma individuals. Finally, in a colonic carcinogenesis model, we detected
      significantly greater hypomethylation in carcinoma than those of dysplastic polyp
      and histological normal colonic epithelium. Thus, the methylation status is a
      unique feature of a specific tissue type and the global hypomethylation is a
      common epigenetic process in cancer, which may progressively evolve during
      multistage carcinogenesis.

PMID- 15480422
TI  - Contig array CGH at 3p14.2 points to the FRA3B/FHIT common fragile region as the
      target gene in diffuse large B-cell lymphoma.
AB  - Deletions of the 3p arm have been detected in various solid tumors, but no study
      to date has investigated this deletion in diffuse large B-cell lymphoma (DLBCL).
      Recently, we demonstrated that 3p14.2 was deleted in approximately 30% of DLBCL
      cases by use of a genome-wide array-comparative genomic hybridization (CGH). For
      a more detailed examination of the genomic losses at 3p14.2, here we made use of
      contig BAC array for 3p14.2, and found that 12 DLBCL samples displayed losses.
      All of the deleted regions were located within the fragile histidine triad (FHIT)
      gene, and the most frequent region of loss was mapped to 0.4 Mbp of the region
      encompassing the introns 4 and 5 and exon 5 of the FHIT gene. Concomitant
      analysis of transcripts showed that the FHIT gene was aberrantly transcribed in
      31% of the DLBCL samples examined and that the lost exons of the aberrant
      transcripts were correlated with genomic deletions. These findings indicate that
      (1) loss of genomic material at 3q14.2 is responsible for exon losses of the FHIT
      gene, and (2) genomic loss of the FHIT gene is one of the causes of the
      generation of aberrant transcripts.

PMID- 15480423
TI  - Profiling the molecular difference between Patched- and p53-dependent
      rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) is a highly malignant tumor that is histologically related
      to skeletal muscle, yet genetic and molecular lesions underlying its genesis and
      progression remain largely unknown. In this study we have compared the molecular
      profiles of two different mouse models of RMS, each associated with a defined
      primary genetic defect known to play a role in rhabdomyosarcomagenesis in man. We
      report that RMS of heterozygous Patched1 (Ptch1) mice show less aggressive growth
      and a greater degree of differentiation than RMS of heterozygous p53 mice. By
      means of cDNA microarray analysis we demonstrate that RMS in Ptch1 mutants
      predominantly express a number of myogenic markers, including myogenic
      differentiation 1, myosin heavy chain, actin, troponin and tropomyosin, as well
      as genes associated with Hedgehog/Patched signaling like insulin-like growth
      factor 2, forkhead box gene Foxf1 and the growth arrest and DNA-damage-inducible
      gene Gadd45a. In sharp contrast, RMS in p53 mutants display higher expression
      levels of cell cycle-associated genes like cyclin B1, cyclin-dependent kinase 4
      and the proliferation marker Ki-67. These results demonstrate that different
      causative mutations lead to distinct gene expression profiles in RMS, which
      appear to reflect their different biological characteristics. Our results provide
      a first step towards a molecular classification of different forms of RMS. If the
      described differences can be confirmed in human RMS our results will contribute
      to a new molecular taxonomy of this cancer, which will be critical for gene
      mutation- and expression-specific therapy.

PMID- 15480424
TI  - Rap1 mutants with increased affinity for the guanine-nucleotide exchange factor
      C3G.
AB  - The mutant of Ras protein with serine to asparagine mutation at residue 17 (Ras
      17N) is known to interfere with the signaling function of the wild-type Ras
      protein by sequestering its guanine-nucleotide exchange factors (GEFs). The
      similar mutant of another Ras family protein Rap1 (Rap1-17N) fails to effectively
      interfere with the interaction between the wild-type Rap1 and one of its GEFs,
      C3G, in vitro. In the present study, we have attempted to isolate Rap1 mutants
      with increased affinity for C3G using random mutagenesis and yeast two-hybrid
      screening. Based on the pattern of mutations found among these mutants, we could
      design a potent C3G-binder, named Rap1-AGE, harboring mutations in three sites
      (17A, 29G, and 117E). The association of Rap1-AGE with C3G in the cells was
      confirmed by co-immunoprecipitation experiments. The ability of Rap1-AGE to
      inhibit C3G-mediated Rap1-activation and cell spreading was also demonstrated. On
      the other hand, Rap1 activation mediated by two other GEFs, Epac and smgGDS, was
      not inhibited by Rap1-AGE. These results suggest that Rap1-AGE acts as a dominant
      interfering factor against C3G and serves as a useful tool in analyzing the roles
      of C3G-Rap1 signaling pathway in various biological processes.

PMID- 15480425
TI  - p38 MAPK inhibition enhances PS-341 (bortezomib)-induced cytotoxicity against
      multiple myeloma cells.
AB  - Although PS-341 (bortezomib) is a promising agent to improve multiple myeloma
      (MM) patient outcome, 65% of patients with relapsed and refractory disease do not
      respond. We have previously shown that heat shock protein (Hsp)27 is upregulated
      after PS-341 treatment, that overexpression of Hsp27 confers PS-341 resistance,
      and that inhibition of Hsp27 overcomes PS-341 resistance. Since Hsp27 is a
      downstream target of p38 mitogen-activated protein kinase (MAPK)/MAPK-mitogen
      activated protein kinase-2 (MAPKAPK2), we hypothesized that inhibition of p38
      MAPK activity could augment PS-341 cytotoxicity by downregulating Hsp27. Although
      p38 MAPK inhibitor SCIO-469 (Scios Inc, CA, USA) alone did not induce significant
      growth inhibition, it blocked baseline and PS-341-triggered phosphorylation of
      p38 MAPK as well as upregulation of Hsp27, associated with enhanced cytotoxicity
      in MM.1S cells. Importantly, SCIO-469 enhanced phosphorylation of c-Jun NH2
      terminal kinase (JNK) and augmented cleavage of caspase-8 and poly(ADP)-ribose
      polymerase. Moreover, SCIO-469 downregulated PS-341-induced increases in G2/M
      phase cells, associated with downregulation of p21Cip1 expression. Importantly,
      SCIO-469 treatment augmented cytotoxicity of PS-341 even against PS-341-resistant
      cell lines and patient MM cells. These studies therefore provide the framework
      for clinical trials of SCIO-469 to enhance sensitivity and overcome resistance to
      PS-341, thereby improving patient outcome in MM.

PMID- 15480427
TI  - Cell type-specific effects of asbestos on intracellular ROS levels, DNA oxidation
      and G1 cell cycle checkpoint.
AB  - Exposure to asbestos fibers increases the risk of development of mesotheliomas
      and lung carcinomas, but not fibrosarcomas. We present data suggesting that
      resistance of fibroblasts to asbestos-induced carcinogenesis is likely to be
      connected with their lower ability to generate reactive oxygen species (ROS) in
      response to asbestos exposure and stricter control of proliferation of cells
      bearing asbestos/ROS-induced injuries. In fact, chrysotile (Mg6Si4O10(OH)8)
      asbestos exposure (5-10 microg/cm2) increased intracellular ROS and 8-oxo-guanine
      contents in rat pleural mesothelial cells, but not in lung fibroblasts.
      Simultaneously, moderate dosages of chrysotile and other agents increasing ROS
      levels (hydrogen peroxide, H2O2 and ethyl-methanesulfonate, EMS) inhibited cell
      cycle progression, in particular G1-to-S transition, in fibroblasts, but not in
      mesothelial cells. The arrested fibroblasts underwent cell death, while the
      majority of chrysotile-treated mesothelial cells survived. The differences in
      cell cycle response to asbestos/ROS-induced injuries correlated with distinct
      activity of p53-p21Cip1/Waf1 pathway in the two cell types. Chrysotile, H2O2 and
      EMS caused p53 upregulation in both cell types, but mesothelial cells, unlike
      fibroblasts, showed no accumulation of p21Cip1/Waf1. Of note, treatment with
      doxorubicin caused similar p53-dependent p21Cip1/Waf1 upregulation and cell cycle
      arrest in both cell types. This suggests differential response of fibroblasts and
      mesothelial cells specifically to asbestos/ROS exposure rather than to all DNA
      damaging insults.

PMID- 15480426
TI  - Thioredoxin modulates activator protein 1 (AP-1) activity and p27Kip1 degradation
      through direct interaction with Jab1.
AB  - Thioredoxin (Trx) is a cellular redox enzyme that plays multiple roles in
      regulating cell growth and apoptosis. Jun activation domain-binding protein 1
      (Jab1) was originally identified as a coactivator of activator protein 1 (AP-1)
      transcription and was also shown to promote degradation of the cyclin-dependent
      kinase inhibitor, p27Kip1. Recently, Jab1 expression was associated with the
      progression and poor prognosis of pituitary, epithelial ovarian, and breast
      cancers, suggesting that it plays a role in oncogenesis. Here, we report that Trx
      specifically interacts with and modulates the function of Jab1. Fluorescence
      resonance energy transfer and co-immunoprecipitation studies revealed that Trx
      and Jab1 colocalize and directly interact with each other. Further, Trx
      negatively regulates two important Jab1-controlled signaling pathways, activation
      of AP-1 transcription and degradation of p27Kip1, probably through a direct
      interaction between Trx and C-terminal of Jab1. The negative effect of Trx on AP
      1 activity is Jab1-dependent, as it disappears when Jab1 levels are suppressed by
      an antisense approach. In addition, Trx competes with p27Kip1 for Jab1 binding.
      Taken together, our results suggest that Trx may regulate cell cycle and growth
      through a novel modulation of Jab1-mediated proliferation signals, further
      indicating that Trx may have the ability to control tumor progression.

PMID- 15480428
TI  - Rho/Rhotekin-mediated NF-kappaB activation confers resistance to apoptosis.
AB  - Rhotekin (RTKN), the gene coding for the Rho effector, RTKN, was shown to be
      overexpressed in human gastric cancer (GC). In this study, we further showed that
      RTKN is expressed at a low level in normal cells and is overexpressed in many
      cancer-derived cell lines. The function of RTKN as an effector protein in Rho
      GTPase-mediated pathways regulating apoptosis was investigated. By transfection
      and expression of RTKN in cells that expressed endogenous RTKN at a low basal
      level, we showed that RTKN overexpression conferred cell resistance to apoptosis
      induced by serum deprivation or treatment with sodium butyrate, and the increased
      resistance correlated to the level of RTKN. Conversely, reducing RTKN expression
      by small interfering RNAs greatly sensitized cells to apoptosis. The RTKN
      mediated antiapoptotic effect was blocked by the nuclear factor-kappaB (NF
      kappaB) inhibitors, curcumin or parthenolide, but not by the phosphatidylinositol
      3'-OH-kinase inhibitor, LY294002, or the MAP kinase inhibitor, PD98059. Reporter
      gene assays and electrophoretic mobility shift assay confirmed that RTKN
      overexpression led to constitutive activation of NF-kappaB through the
      phosphorylation of IkappaB by IKKbeta. By using the RTKN truncation mutants, we
      showed that RTKN mediated Rho activity eliciting signaling pathway to activate NF
      kappaB, with a concomitant induction of expression of the NF-kappaB antiapoptotic
      genes, cIAP-2, BCl-xL, A1, and A20. Consistent with these data, RTKN-expressing
      cells showed increased chemoresistance to 5-fluorouracil and paclitaxol, and the
      resistance was greatly attenuated by NF-kappaB inhibitor. In conclusion,
      overactivated Rho/RTKN/NF-kappaB signaling pathway through overexpression of RTKN
      may play a key role in gastric tumorigenesis by conferring cells resistance to
      apoptosis, and this signaling pathway may serve as an important target for novel
      therapeutic approaches to the treatment of human GC.

PMID- 15480429
TI  - Isolation and characterization of a novel gene CLUAP1 whose expression is
      frequently upregulated in colon cancer.
AB  - To disclose mechanisms of colorectal carcinogenesis and identify novel diagnostic
      markers and drug targets for treatment of these tumors, we previously analysed
      the expression profiles of 11 colorectal cancers using a genome-wide cDNA
      microarray containing 23,040 genes. Among the genes commonly transactivated in
      the cancers, we identified a novel human gene, which we termed CLUAP1 (clusterin
      associated protein 1). It encodes a nuclear protein of 413 amino acids containing
      a coiled-coil domain. To investigate its function, we searched for CLUAP1
      interacting proteins using yeast two-hybrid system and identified nuclear
      Clusterin. Expression of CLUAP1 was gradually increased in the late S to G2/M
      phases of cell cycle and it returned to the basal level in the G0/G1 phases.
      Suppression of this gene by short interfering RNAs resulted in growth retardation
      in the transfected cells. These data provide better understanding of colorectal
      carcinogenesis, and inactivation of CLUAP1 may conceivably serve in the future as
      a novel therapeutic intervention for treatment of colon cancer.

PMID- 15480430
TI  - Redistribution of CD95, DR4 and DR5 in rafts accounts for the synergistic
      toxicity of resveratrol and death receptor ligands in colon carcinoma cells.
AB  - The natural phytoalexin resveratrol (3, 5, 4'-trihydroxystilbene) exhibits both
      chemopreventive and antitumor activities through a variety of mechanisms. We have
      shown previously that resveratrol-induced apoptosis of a human colon cancer cell
      line involved the redistribution of CD95 (Fas/Apo-1) into lipid rafts. Here, we
      show that, in colon cancer cells that resist to resveratrol-induced apoptosis,
      the polyphenol also induces a redistribution of death receptors into lipid rafts.
      This effect sensitizes these tumor cells to death receptor-mediated apoptosis. In
      resveratrol-treated cells, tumor necrosis factor (TNF), anti-CD95 antibodies and
      TNF-related apoptosis-inducing ligand (TRAIL) activate a caspase-dependent death
      pathway that escapes Bcl-2-mediated inhibition. Resveratrol does not enhance the
      number of death receptors at the surface of tumor cells but induces their
      redistribution into lipid rafts and facilitates the caspase cascade activation in
      response to death receptor stimulation. The cholesterol sequestering agent
      nystatin prevents resveratrol-induced death receptor redistribution and cell
      sensitization to death receptor stimulation. Thus, whatever its ability to induce
      apoptosis in a tumor cell, resveratrol induces redistribution of death receptors
      into lipid rafts. This redistribution sensitizes the cells to death receptor
      stimulation. Such a sensitizing effect may be of therapeutic interest if TRAIL
      agonists are introduced in clinics.

PMID- 15480431
TI  - Activation of mitochondrial apoptotic pathway in mantle cell lymphoma: high
      sensitivity to mitoxantrone in cases with functional DNA-damage response genes.
AB  - Mantle cell lymphoma (MCL) is a mature B-cell proliferation characterized by the
      presence of translocation t(11;14)(q13;q32), an aggressive clinical course, and
      poor response to chemotherapy. The majority of drugs currently used in the
      treatment of lymphoproliferative disorders induce cell death by triggering
      apoptosis, but few data concerning drug-induced apoptosis in MCL have been
      reported. We have analysed the mechanisms of drug-induced cell death in four cell
      lines with the t(11;14) and in primary cells from 10 patients with MCL.
      Mitoxantrone, a topoisomerase II inhibitor, induced a strong cytotoxic effect in
      three cell lines (JVM-2, REC-1, and Granta 519), and in primary MCL cells. This
      cytotoxic effect due to apoptosis induction was observed despite the presence of
      either p53 or ATM abnormalities. However, no cytotoxic effect was detected after
      incubation with DNA-damaging agents in the NCEB-1 cell line, carrying p53 and ATM
      alterations, despite the presence of functional mitochondrial machinery. These
      results support that mitoxantrone can be effective in the treatment of MCL but
      that this activity requires the integrity of functional DNA-damage response
      genes.

PMID- 15480432
TI  - An HSP90-mimic peptide revealed by fingerprinting the pool of antibodies from
      ovarian cancer patients.
AB  - To gain insight into the mechanisms of molecular recognition and humoral immune
      response in ovarian cancer, we used fingerprinting, a phage display-based
      combinatorial selection to isolate peptide ligands to tumor-related antibodies
      present in ascites from patients with advanced disease. First, we have isolated a
      consensus motif (sequence CVPELGHEC) in 86% of the peptides screened; this
      enriched motif was selected from a total of 10(8)-10(9) unique random sequences
      present in the library. Next, we identified the heat-shock protein 90 kDa (HSP90)
      as the native antigen mimicked by the motif. Finally, we evaluated the expression
      of HSP90 and the presence of antibodies against the HSP90-mimic peptide in a
      large panel of ovarian cancer patients and controls. In tissue microarrays, we
      show that the expression of HSP90 is ubiquitous. However, the corresponding
      humoral immune response against HSP90 is restricted to a subset of patients with
      stage IV disease. Together, these results show that screening humoral response
      can identify tumor antigens that may serve as molecular targets in ovarian
      cancer. Recognition of such relevant proteins in the immunobiology of malignant
      tumors may lead to the development of therapies

PMID- 15480433
TI  - Frequent hypermethylation of RASSF1A in early flat-type colorectal tumors.
AB  - Flat colorectal tumors, characterized by high-grade dysplasia from early small
      flat mucosal lesions, exhibit a relatively aggressive clinical behavior and are
      known for their infrequent K-ras mutations. In this study, we investigated the
      methylation status of the RASSF1A promoter in association with 3p LOH and K-ras
      mutations in 48 flat colorectal tumors (39 early carcinomas and nine intramucosal
      high-grade dysplasias). RASSF1A hypermethylation was detected in 39 of 48 (81.3%)
      tumors and RASSF1A methylation was also detected in 19 of 39 (49%) normal colonic
      mucosal tissues. 3p21.3 LOH was detected in 20 of 42 (47.6%) cases, but RASSF1
      methylation was detected in cases with LOH (14 cases) and retention of 3p21.3 (20
      cases). K-ras mutations were detected in seven of 48 (14.6%) tumors and the
      concordant occurrence of K-ras mutation and RASSF1A methylation was detected in
      three of 48 cases (6.3%). Overall, there was a statistically significant mutually
      exclusive relationship between K-ras mutations and RASSF1A methylation. In
      conclusion, promoter hypermethylation of RASSF1A is a frequent event and may
      start early in the background normal mucosa in this tumor type. An alternative
      cascade of abnormalities in RAS transduction pathways may be responsible for the
      flat morphology and aggressive nature of flat colorectal neoplasms.

PMID- 15480435
TI  - Impaired neutralising antibody formation and high transduction efficacy after
      isolated hepatic perfusion with adenoviral vectors.
AB  - Local adenoviral gene transfer can be performed by means of isolated hepatic
      perfusion (IHP). This methodology is a very effective and safe way to deliver
      adenoviral vectors. We studied the immune response after IHP. A decreased
      neutralising antibody formation was observed, offering possibilities for further
      research in the field of gene therapy in isolated perfusion settings.

PMID- 15480434
TI  - Expression and co-expression of the members of the epidermal growth factor
      receptor (EGFR) family in invasive breast carcinoma.
AB  - The epidermal growth factor receptor (EGFR) family plays an important role in
      breast carcinogenesis. Much interest has been focused recently on its members
      because of their potential role as prognostic indicators in breast cancer and
      their involvement in cancer therapy. We have evaluated more than 1500 cases of
      invasive breast carcinoma immunohistochemically using tissue microarray
      technology to examine the expression of EGFR family receptor proteins. We have
      found that 20.1 and 31.8% of cases were positive for EGFR and c-erbB-2,
      respectively, and 45 and 45.1% of tumours overexpressed for c-erbB-3 and c-erbB
      4, respectively. The expression of either EGFR or c-erbB-2 was associated with
      other bad prognostic features and with poor outcome. Neither c-erbB-3 nor c-erbB
      4 had any association with survival. c-erbB-2 had an independent prognostic
      effect on overall and disease-free survival (DFS) in all cases, as well as in the
      subset of breast carcinoma patients with nodal metastases. Several hetero- and
      homodimeric combinations have been reported between the EGFR members. Those
      dimers can evoke diverse signal transduction pathways with variable cellular
      responses. We stratified cases according to their co-expression of receptors into
      distinct groups with different receptor-positive combinations. Patients whose
      tumours co-expressed c-erbB-2 and c-erbB-3, as well as those whose tumours co
      expressed EGFR, c-erbB-2 and c-erbB-4 showed an unfavourable outcome compared
      with other groups, while combined c-erbB-3 and c-erbB-4 expression was associated
      with a better outcome. In cases showing expression of one family member only
      (homodimers), we found a significant association between c-erbB-4 homodimer
      expressing tumours and better DFS. In contrast, patients with c-erbB-2 homodimer
      expressing tumours had a significant poorer DFS compared with other cases. These
      data imply that the combined profile expression patterns of the four receptor
      family members together provide more accurate information on the tumour behaviour
      than studying the expression of each receptor individually.

PMID- 15480436
TI  - Complementary and Alternative Medicine: a Japanese Perspective.

PMID- 15480437
TI  - Evidence-based Reconstruction of Kampo Medicine: Part II-The Concept of Sho.

PMID- 15480438
TI  - An Overview of Traditional Chinese Herbal Formulae and a Proposal of a New Code
      System for Expressing the Formula Titles.
AB  - Traditional Chinese herbal therapy can be characterized by the use of a large
      number of multi-herb formulae. To provide modern and Western scientists without
      knowledge of Chinese literature and cultural background easy access to
      information, a database with a total of 11 810 traditional Chinese herbal
      formulae was constructed. All the information was then translated into
      understandable scientific terms in English. While coining the formula titles in
      English, we discovered some principles governing the naming of titles by using
      computer analysis. In addition, we observed that about 92% of the formulae are in
      the range of single-herb formulae to thirteen-herb formulae. Most large number
      herb formulae are formulated by combining pre-existing smaller number-herb
      formulae. The King herbs () with major therapeutic activity in a multi-herb
      formula were identified by the formulation concept using two parameters: the
      herbal dose and the herbal drug property (the degree of toxicity). Based on such
      analytical data, we established an English code system representing all formula
      titles written in ideographic Chinese characters: an array of important key words
      such as 'Herbal name in Latin + Efficacy (Target organs) + Preparation form +
      Number of herbs.' By searching the English version of the database with any of
      the above key words, a variety of information on the status of traditional
      Chinese herbal therapy can be accessed.

PMID- 15480439
TI  - Traditional and Modern Biomedical Prospecting: Part II-the Benefits: Approaches
      for a Sustainable Exploitation of Biodiversity (Secondary Metabolites and
      Biomaterials from Sponges).
AB  - The progress in molecular and cell biology has enabled a rational exploitation of
      the natural resources of the secondary metabolites and biomaterials from sponges
      (phylum Porifera). It could be established that these natural substances are
      superior for biomedical application to those obtained by the traditional
      combinatorial chemical approach. It is now established that the basic structural
      and functional elements are highly conserved from sponges to the crown taxa
      within the Protostomia (Drosophila melanogaster and Caenorhabditis elegans) and
      Deuterostomia (human); therefore, it is obvious that the molecular etiology of
      diseases within the metazoan animals have a common basis. Hence, the major
      challenge for scientists studying natural product chemistry is to elucidate the
      target(s) of a given secondary metabolite, which is per se highly active and
      selective. After this step, the potential clinical application can be approached.
      The potential value of some selected secondary metabolites, all obtained from
      sponges and their associated microorganisms, is highlighted. Examples of
      compounds that are already in medical use (inhibition of tumor/virus growth
      [arabinofuranosyl cytosine and arabinofuranosyl adenine]), or are being
      considered as lead structures (acting as cytostatic and anti-inflammatory
      secondary metabolites [avarol/avarone], causing induction of apoptosis
      [sorbicillactone]) or as prototypes for the interference with metabolic pathways
      common in organisms ranging from sponges to humans (modulation of pathways
      activated by fungal components [aeroplysinin], inhibition of angiogenesis [2
      methylthio-1,4-napthoquinone], immune modulating activity [FK506]) are discussed
      in this study. In addition, bioactive proteins from sponges are listed
      (antibacterial activity [pore-forming protein and tachylectin]). Finally, it is
      outlined that the skeletal elements-the spicules-serve as blueprints for new
      biomaterials, especially those based on biosilica, which might be applied in
      biomedicine. These compounds and biomaterials have been isolated/studied by
      members of the German Center of Excellence BIOTECmarin. The goal for the future
      is to successfully introduce some of these compounds in the treatment of human
      diseases in order to raise the public awareness on the richness and diversity of
      natural products, which should be sustainably exploited for human benefit.

PMID- 15480441
TI  - Exercise and Life-Satisfactory-Fitness: Complementary Strategies in the
      Prevention and Rehabilitation of Illnesses.
AB  - Moderate training of an endurance nature, but also other exercise activities, not
      only has a preventive effect on various illnesses and pre-illness states such as
      the metabolic syndrome and cancer, but is also effective in treating patients in
      the rehabilitation phase after illness, e.g. cardiovascular or cancer. Our
      investigation demonstrates that even low level physical activity has a very good
      preventive effect too, which is enhanced when it is accompanied by mental
      activity and psychological well-being. In total, we investigated 13 000 people on
      the basis of socio-economic panel polls with respect to life contentment, health
      status and leisure-time activities. Life contentment is positively linked to
      contentment with labor, which seems to be an essential aspect with regard to the
      increasing number of unemployed people in Europe. The second important factor is
      health-promoting activities during leisure time. Exercise, especially, has a
      significant influence on life satisfaction as a feeling of physical fitness
      feeling is regarded as synonymous with good health. The results underline the
      psycho-neuroimmunological network, which stabilizes our health and shows that
      different activities in older adults have a significant effect on the aging
      process and age-related illnesses. Besides the various activities that are
      important in this arena, namely muscle and mental mobility ('brawn and brain'), a
      third component must be taken into consideration: life contentment in the form of
      a successful retrospective view and a positive outlook, embedded in a
      psychosocial family environment ('brood') and integrated in a stress-free
      biotope, where life does make sense. Alternative and complementary strategies
      should be considered in light of these three aspects when we think about
      additional anti-inflammatory strategies in preventing diseases or treating them
      and their relapses. Sport has made a few healthy people ill, but sport has also
      made a good few of ill people healthy! (Gerhard Uhlenbruck, Aphorisms).

PMID- 15480440
TI  - An Alternative Approach to Atopic Dermatitis: Part II-Summary of Cases and
      Discussion.
AB  - In the first part of this Review, we presented case-series where Kampo treatment
      was introduced for those atopic dermatitis (AD) patients who had failed with
      conventional therapy, in an attempt to prove that there exists a definite
      subgroup of AD patients for whom Kampo treatment is effective. In this second
      part, we will first provide the summary of the results for 140 AD patients we
      treated in 2000. The results suggest that Kampo treatment is effective for more
      than half of AD patients who fail with conventional therapy. In the Discussion,
      we will examine the evidential basis for conventional AD therapy and discuss how
      Kampo treatment should be integrated into the guidelines for AD therapy. We
      contend that Kampo treatment should be tried before systematic immunosuppressive
      agents are considered. As each Kampo treatment is highly individualized, it
      should be regarded more as 'art' than technology, and special care should be
      taken to assess its efficacy in clinical trial.

PMID- 15480442
TI  - Antiprotozoan and Antiviral Activities of Non-cytotoxic Truncated and Variant
      Analogues of Mussel Defensin.
AB  - We previously reported the crucial role displayed by loop 3 of defensin isolated
      from the Mediterranean mussel, Mytilus galloprovincialis, in antibacterial and
      antifungal activities. We now investigated antiprotozoan and antiviral activities
      of some previously reported fragments B, D, E, P and Q. Two fragments (D and P)
      efficiently killed Trypanosoma brucei (ID(50) 4-12 MUM) and Leishmania major
      (ID(50) 12-45 MUM) in a time/dose-dependent manner. Killing of T. brucei started
      as early as 1 h after initiation of contact with fragment D and reached 55%
      mortality after 6 h. Killing was temperature dependent and a temperature of 4
      degrees C efficiently impaired the ability to kill T. brucei. Fragments bound to
      the entire external epithelium of T. brucei. Prevention of HIV-1 infestation was
      obtained only with fragments P and Q at 20 MUM. Even if fragment P was active on
      both targets, the specificity of fragments D and Q suggest that antiprotozoan and
      antiviral activities are mediated by different mechanisms. Truncated sequences of
      mussel defensin, including amino acid replacement to maintain 3D structure and
      increased positive net charge, also possess antiprotozoan and antiviral
      capabilities. New alternative and/or complementary antibiotics can be derived
      from the vast reservoir of natural antimicrobial peptides (AMPs) contained in
      marine invertebrates.

PMID- 15480443
TI  - Comparison of Radical Scavenging Activity, Cytotoxic Effects and Apoptosis
      Induction in Human Melanoma Cells by Taiwanese Propolis from Different Sources.
AB  - Propolis is a sticky substance that is collected from plants by honeybees. We
      previously demonstrated that propolins A, B, C, D, E and F, isolated from
      Taiwanese propolis (TP), could effectively induce human melanoma cell apoptosis
      and were strong antioxidant agents. In this study, we evaluated TP for free
      radical scavenging activity by DPPH (1,2-diphenyl-2-picrylhydrazyl). The phenolic
      concentrations were quantified by the Folin-Ciocalteu method. The apoptosis
      trigger activity in human melanoma cells was evaluated. TP contained a higher
      level of phenolic compounds and showed strong capability to scavenge free
      radicals. Additionally, TP1g, TP3, TP4 and TP7 exhibited a cytotoxic effect on
      human melanoma cells, with an IC(50) of approximately 2.3, 2.0, 3.3 and 3.3
      MUg/ml, respectively. Flow cytometric analysis for DNA fragmentation indicated
      that TP1g, TP2, TP3 and TP7 could induce apoptosis in human melanoma cells and
      there is a marked loss of cells from the G2/M phase of the cell cycle. To address
      the mechanism of the apoptosis effect of TP, we evaluated its effects on
      induction of apoptosis-related proteins in human melanoma cells. The levels of
      procaspase-3 and PARP [poly(ADP-ribose) polymerase] were markedly decreased.
      Furthermore, propolins A, B, C, D, E and F in TP were determined using HPLC. The
      results indicate that TP is a rich source of these compounds. The findings
      suggest that TP induces apoptosis in human melanoma cells due to its high level
      of propolins.

PMID- 15480444
TI  - Study on Application of Static Magnetic Field for Adjuvant Arthritis Rats.
AB  - In order to examine the effectiveness of the application of static magnetic field
      (SMF) on pain relief, we performed a study on rats with adjuvant arthritis (AA).
      Sixty female Sprague-Dawley (SD) rats (age: 6 weeks, body weight: approximately
      160 g) were divided into three groups [SMF-treated AA rats (Group I), non-SMF
      treated AA rats (Group II) and control rats (Group III)]. The SD rats were
      injected in the left hind leg with 0.6 mg/0.05 ml Mycobacterium butyrium to
      induce AA. The rats were bred for 6 months as chronic pain model. Thereafter, the
      AA rats were or were not exposed to SMF for 12 weeks. We assessed the changes in
      the tail surface temperature, locomotor activity, serum inflammatory marker and
      bone mineral density (BMD) using thermography, a metabolism measuring system and
      the dual-energy X-ray absorptiometry (DEXA) method, respectively. The tail
      surface temperature, locomotor activity and femoral BMD of the SMF-exposed AA
      rats were significantly higher than those of the non-SMF-exposed AA rats, and the
      serum inflammatory marker was significantly lower. These findings suggest that
      the pain relief effects are primarily due to the increased blood circulation
      caused by the rise in the tail surface temperature. Moreover, the pain relief
      effects increased with activity and BMD of the AA rats.

PMID- 15480446
TI  - Effect of Hochu-ekki-to (TJ-41), a Japanese Herbal Medicine, on Daily Activity in
      a Murine Model of Chronic Fatigue Syndrome.
AB  - We aimed to evaluate the effect of a Japanese herbal medicine, Hochu-ekki-to (TJ
      41), on daily activity in a murine model of chronic fatigue syndrome (CFS). CFS
      was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks.
      TJ-41 was orally administered to mice in a dose of 500 mg/kg/day for 1 week
      before injecting BA and for 4 weeks thereafter. We evaluated daily running
      activity in mice receiving TJ-41 as compared with that in untreated mice.
      Survival of both mouse groups was also monitored during the observation period.
      Body weight (BW), spleen weight (SW), SW/ BW ratio and expression levels of
      interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time
      of sacrifice. The daily activity was significantly higher in the treated group
      than in the control. Two mice in the untreated group died 2 days after the second
      injection of BA, whereas no mice in the group treated with TJ-41 died. The SW and
      SW/BW ratio were significantly lower in the treated mice than in the control.
      Suppressed IL-10 mRNA levels were observed in the spleens of the mice treated
      with TJ-41. Our data suggest that Hochu-ekki-to might possess an inhibitory
      effect on the marked decrease in running activity following BA injection.

PMID- 15480445
TI  - Mediation of Endogenous beta-endorphin by Tetrandrine to Lower Plasma Glucose in
      Streptozotocin-induced Diabetic Rats.
AB  - The role of beta-endorphin in the plasma glucose-lowering action of tetrandrine
      in streptozotocin-induced diabetic rats (STZ-diabetic rats) was investigated. The
      plasma glucose concentration was assessed by the glucose oxidase method. The
      enzyme-linked immunosorbent assay was used to determine the plasma level of beta
      endorphin-like immunoreactivity (BER). The mRNA levels of glucose transporter
      subtype 4 (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK)
      in the liver of STZ-diabetic rats were detected by Northern blotting analysis.
      The expressed protein of GLUT4 or PEPCK was characterized by Western blotting
      analysis. Tetrandrine dose-dependently increased plasma BER in a manner parallel
      to the decrease of plasma glucose in STZ-diabetic rats. Moreover, the plasma
      glucose-lowering effect of tetrandrine was inhibited by naloxone and naloxonazine
      at doses sufficient to block opioid MU-receptors. Further, tetrandrine failed to
      produce plasma glucose-lowering action in opioid MU-receptor knockout diabetic
      mice. Bilateral adrenalectomy eliminated the plasma glucose-lowering effect and
      plasma BER-elevating effect of tetrandrine in STZ-diabetic rats. Both effects
      were abolished by treatment with hexamethonium or pentolinium at doses sufficient
      to block nicotinic receptors. Tetrandrine enhanced BER release directly from the
      isolated adrenal medulla of STZ-diabetic rats and this action was abolished by
      the blockade of nicotinic receptors. Repeated intravenous administration of
      tetrandrine (1.0 mg/kg) to STZ-diabetic rats for 3 days resulted in an increase
      in the mRNA and protein levels of the GLUT4 in soleus muscle, in addition to the
      lowering of plasma glucose. Similar treatment with tetrandrine reversed the
      elevated mRNA and protein levels of PEPCK in the liver of STZ-diabetic rats. The
      obtained results suggest that tetrandrine may induce the activation of nicotinic
      receptors in adrenal medulla to enhance the secretion of beta-endorphin, which
      could stimulate opioid MU-receptors to increase glucose utilization or/and reduce
      hepatic gluconeogenesis to lower plasma glucose levels in STZ-diabetic rats.

PMID- 15480447
TI  - Commentary on Traditional and Modern Biomedical Prospecting: Part II-The Benefits
      by Werner E.G. Muller, Heinz C. Schroder, Matthias Wiens, Sanja Perovic-Ottstadt,
      Renato Batel and Isabel M. Muller: Anti-protozoa and antiviral activities of non
      cytotoxic truncated and variant analogues of mussel defensin by P. Roch, A.
      Beschin and E. Bernard.

PMID- 15480448
TI  - Conformationally controlled high-affinity targeting of RNA or DNA by novel 2'
      amino-DNA/LNA mixmers and pyrenyl-functionalized 2'-amino-DNA.
AB  - 9-Mer DNA sequences containing 2'-N-methyl-2'-N-(pyren-1-ylmethyl)-2'-amino-DNA
      monomers display significantly increased affinity towards DNA complements whereas
      the corresponding 2'-amino-DNA monomer has a detrimental effect on duplex
      stability. These effects are efficiently reversed by incorporation of four LNA
      nucleotides inducing a B-DNA to A-DNA conformational change.

PMID- 15480450
TI  - Aza-Reformatsky-type reaction of alpha-iodomethyl ketone O-alkyl oximes promoted
      by titanium tetraiodide.
AB  - Titanium tetraiodide promotes an aza-Reformatsky-type reaction of alpha
      iodomethyl ketone O-alkyl oximes with carbonyl compounds to give beta-hydroxy
      ketone O-alkyl oximes in good to high yields.

PMID- 15480449
TI  - Preparation and relevance of a cross-coupling product between sinapyl alcohol and
      sinapyl p-hydroxybenzoate.
AB  - Cross-coupling of sinapyl p-hydroxybenzoate and sinapyl alcohol produces an 8-8
      cross-coupled product that is also detected in lignifying poplar tissues,
      implicating sinapyl p-hydroxybenzoate as a lignin precursor.

PMID- 15480451
TI  - MgI2-catalyzed halo aldol reaction: a practical approach to (E)-beta-iodovinyl
      beta'-hydroxyketones.
AB  - A novel generation of 1-iodo-3-siloxy-1,3-butadienes has been developed by
      reacting trimethylsilyl iodide (TMS-I) with alpha, beta-unsaturated ketones in
      dichloromethane at 0 degrees C without the use of any catalyst. The halo aldol
      reaction of these butadiene intermediates with aldehydes was efficiently carried
      out by using magnesium iodide as the catalyst. Twelve beta-iodo-alpha,beta
      unsaturated-beta'-hydroxyketones (halo aldols) have been synthesized under the
      new condition with excellent geometric selectivity and good chemical yields (>80%
      chemical yields for 11 examples).

PMID- 15480452
TI  - Synthesis and ligand properties of thianthrenophane.
AB  - Thianthrenophane 1 has a cavity which offers enough room to potentially enable
      endohedral coordination to small ions or molecules. For the complexation of
      silver(I) perchlorate the complex stability constants of 1 logK1=5.45 +/- 0.13
      and of thianthrene logK2=9.16 +/- 0.10 were determined by UV/Vis titration.
      Single competition transport experiments with ten metal salts demonstrate a very
      high selectivity of 1 as a carrier for silver(I) and a distinctly higher
      transport rate compared to carriers such as thianthrene and 1,4,8,11
      tetrathiacyclotetradecane (14-ane-S4). Although the X-ray crystal structure
      analysis of the polymeric [Ag(1)]ClO4.(dioxane)7 complex shows an exohedral
      coordination to silver(I) we suggest that the formation of an endohedral [Ag(1)]+
      complex is the explanation for the unusual carrier selectivity of silver(I) by 1
      in bulk liquid membrane.

PMID- 15480453
TI  - Circular dichroism spectroscopic studies reveal pH dependent binding of curcumin
      in the minor groove of natural and synthetic nucleic acids.
AB  - For the first time, an interaction between the non-toxic, cancer chemopreventive
      agent curcumin and both natural and synthetic DNA duplexes has been demonstrated
      by using circular dichroism (CD) and absorption spectroscopy techniques. Upon
      addition of curcumin to calf thymus DNA, poly(dG-dC).poly(dG-dC) and poly(dA
      dT).poly(dA-dT) solutions, an intense positive induced CD band centered around
      460-470 nm was observed depending on the actual pH and Na+ ion concentration of
      the medium; no CD signal was obtained, however, with single stranded poly(dC).
      Interaction of curcumin with calf thymus DNA was observed already at pH 6.5 in
      contrast with poly(dG-dC).poly(dG-dC) which induces no extrinsic Cotton effect
      above a pH value of 5. The protonated, Hoogsteen base-paired structure of poly(dG
      dC).poly(dG-dC) is necessary for curcumin binding while the alternating AT-rich
      polymer formed complexes with curcumin only at certain Na+ concentrations.
      Evaluation of the spectral data and molecular modeling calculations suggested
      that curcumin, this dietary polyphenolic compound binds in the minor groove of
      the double helix. The mechanism of the induced CD activity, the effects of the pH
      and Na+ ions on the ligand binding and conformation of the double helix are
      discussed in detail. As well as being an essentially new phenolic minor groove
      binder agent curcumin is also a promising molecular probe to study biologically
      important, pH and cation induced conformational polymorphisms of nucleic acids.

PMID- 15480454
TI  - Supramolecular aggregates between carboxylate anions and an octaaza macrocyclic
      receptor.
AB  - The 28-membered octaazamacrocycle Me2[28]py2N6 was used as a receptor for the
      molecular recognition of aromatic and aliphatic carboxylate substrates. The
      receptor-substrate binding behaviour of (H6Me2[28]py2N6)6+ with an aliphatic (
      O2C(CH2)nCO2-, n=0 to 4) and an aromatic (phthalate, isophthalate, terephthalate,
      4,4'-dibenzoate, benzoate, 3- and 4-nitrobenzoate) series of carboxylate anions
      was evaluated by 1H NMR spectroscopy (carried out in DMSO-d6 at 300 K). Two
      association constants were found for most of the studied cases, except for 3- and
      4-nitrobenzoate for which only K1 was determined. For oxalate, malonate, benzoate
      and dibenzoate anions only the beta2 constants could be obtained. The values of
      the first association constant cover a range from 2.86 to 3.69 (log units), and
      the second stepwise constant from 2.15 to 2.89 (also in log units). No special
      selectivity was found but the highest values were determined for adipate and the
      lowest for the monoprotic 3- and 4-nitrobenzoates. Single crystal X-ray
      structures of H6Me2[28]py2N6 6+ with terephthalate, 1, and 4,4'-dibenzoate (2)
      were determined showing supramolecular entities with general formula
      (H6Me2[28]py2N6).(substrate)2(PF6)2.4H2O. These anions are the building blocks of
      an extensive 3-D network of hydrogen bonds.

PMID- 15480455
TI  - Solvent affects the conformation of virginiamycin M1 (pristinamycin IIA,
      streptogramin A).
AB  - The streptogramins are antibiotics which act by binding two different components
      at separate nearby sites on the bacterial 50S ribosome, inhibiting protein
      synthesis. The first component, a macrolactone, is common to many of the
      streptogramin antibiotics and, thus, is referred to by many names including
      virginiamycin M1(VM1), pristinamycin IIA, ostreogrycin A and streptogramin A. X
      Ray crystallographic studies of VM1 bound to ribosomes and to a deactivating
      enzyme show a different conformation to that of VM1 in chloroform solution. We
      now report the results of high resolution 2D NMR experiments that show that the
      conformation of VM1 in dimethyl sulfoxide and methanol differs from both that in
      chloroform solution and in the bound form. The 3D structure and the 1H NMR and
      13C NMR chemical shifts of VM1 in dimethyl sulfoxide and methanol are described.

PMID- 15480456
TI  - Tetrapeptides induce selective recognition for G-quadruplexes when conjugated to
      a DNA-binding platform.
AB  - 3,6-Bis-peptide acridine and acridone conjugates have been designed and
      synthesised to selectively interact with G-quadruplex DNA. The ligand properties
      are peptide sequence dependent, the highest discrimination being obtained with
      the FRHR tetrapeptide (up to >50-fold specificity). Molecular modeling studies
      have helped us rationalise the data and suggest that human telomeric quadruplex
      DNA can readily accommodate tetrapeptides, and furthermore that FRHR contributes
      to stabilization of the complex by non-bonded interactions within the TTA loop
      pockets of the quadruplex. These studies indicate that targeting distinct
      features of a G-quadruplex with hybrid molecules is a promising strategy for
      discriminating between quadruplex and duplex DNA.

PMID- 15480457
TI  - Highly stereoselective oxy-Michael additions to alpha,beta-disubstituted nitro
      olefins: asymmetric synthesis of pseudo-norephedrine derivatives and THP*
      protected alpha-hydroxy ketones.
AB  - The "naked" anion of (S)-6-methyl delta lactol undergoes efficient oxy-Michael
      addition to alpha,beta-disubstituted nitro olefins to give the THP* protected
      Henry products with excellent (95-->98% de) stereocontrol at the beta-position
      and moderate (up to 3 : 1) stereocontrol at the alpha-position in favour of the
      syn-diastereoisomer. Nitro group reduction with in situN-Boc protection and THP*
      removal provides alpha,beta-disubstituted ethanolamine derivatives, while
      treatment with tetrapropylammonium perruthenate gives THP* protected alpha
      hydroxy ketone derivatives in high diasteromeric excess.

PMID- 15480458
TI  - Anion binding properties of 5,5'-dicarboxamido-dipyrrolylmethanes.
AB  - A series of 5,5'-dicarboxamido-dipyrrolylmethanes have been synthesized and in
      some cases crystallographically characterized. Proton NMR titrations have
      revealed that these compounds, that contain only four neutral hydrogen bond
      donors and are acyclic, selectively bind anions in very competitive solvent media
      such as DMSO-d6/water mixtures.

PMID- 15480459
TI  - Synthetic 6-aryl-2-hydroxy-6-ketohexa-2,4-dienoic acid substrates for C-C
      hydrolase BphD: investigation of a general base catalytic mechanism.
AB  - A chemical synthesis of the 2-hydroxy-6-ketohexa-2,4-dienoic acid intermediates
      on bacterial meta-cleavage pathways has been established, using a Heck coupling
      strategy. Coupling of ethyl 3-bromo-2-acetoxyacrylate with 1-aryl vinyl ketals or
      1-aryl allylic alcohols proceeded in 70-90% yield. Heck coupling with an alkyl
      vinyl ketal was also successful, allowing the synthesis of an alkyl-substituted
      ring fission intermediate. The synthetic ring fission intermediates were used to
      investigate the enzymatic reaction catalysed by C-C hydrolase BphD from
      Pseudomonas LB400. A reduced substrate analogue 2,6-dihydroxy-6-phenylhexa-2,4
      dienoic acid was processed enzymatically to benzaldehyde by C-C hydrolase BphD,
      consistent with a catalytic mechanism involving general base-catalysed attack of
      water to give a gem-diol intermediate, and not consistent with a nucleophilic
      mechanism. A series of para-substituted 2-hydroxy-6-keto-6-phenylhexa-2,4-dienoic
      acid substrates were assayed against BphD, and the derived Hammett plot (rho=
      0.71) is consistent with a departing carbanion in the transition state for C-C
      cleavage.

PMID- 15480460
TI  - Synthesis of anti-tumour phosphatidylinositol analogues from glucose by the use
      of ring-closing olefin metathesis.
AB  - A divergent strategy is described for synthesis of the novel
      phosphatidylinositols 1-3. The synthetic approach commences from benzyl-protected
      methyl 6-iodo-6-deoxy-alpha-D-glucopyranoside, which undergoes zinc-mediated
      reductive fragmentation followed by vinyl Grignard addition and ring-closing
      metathesis to afford the key conduritol B intermediate 7. This can trifurcate to
      form three different benzyl-protected myo-inositol headgroups 4-6, which after
      phosphorylation and attachment of the glycerolipid part give
      phosphatidylinositols 1-3. Preliminary biological testing against human colon
      adenocarcinoma cells reveals that analogues 1-3 are significant anti-tumour
      agents.

PMID- 15480461
TI  - Building blocks for cyclotriveratrylene-based coordination networks.
AB  - The incorporation of three-fold symmetric organic host molecules into
      coordination polymers should allow for the construction of new and interesting
      network structures, capable of multiple inclusion behaviour. A range of new multi
      dentate bridging ligands/molecular hosts have been prepared by appending nitrogen
      containing heterocycles to either cyclotricatechylene, or cyclotriguaiacylene
      cores. These compounds were obtained in a single-step reaction from readily
      available precursors, with moderate to good yields, and characterised by a
      combination of NMR spectroscopy, mass spectrometry and elemental analysis. Two of
      the new compounds were characterised by X-ray crystallography, revealing
      different modes of self inclusion behaviour, which indicate the potential
      importance of [small pi]-donor stabilisation by CTV derivatives in host-guest
      chemistry.

PMID- 15480462
TI  - Self-assembly of two-component peptidic dendrimers: dendritic effects on gel
      phase materials.
AB  - The self-assembly of diaminododecane solubilised by different dendritic peptides,
      possessing increasing levels of dendritic branching, was investigated. The
      dendritic peptides were based on l-lysine building blocks and were of first,
      second and third generation, containing one, three and seven amino acid repeat
      units respectively. By applying these structures as potential gelator units, the
      dendritic effect on gelation was investigated. The degree of structuring was
      modulated, with the dendritic peptide controlling the aggregate morphology and
      the ability of the self-assembled state to manifest itself macroscopically as
      gelation. First generation gelator units (G1) did not induce macroscopic gelation
      with diaminododecane under any conditions, whilst those self-assemblies based on
      second (G2) and third (G3) generation branches did form gel-phase materials.
      Furthermore, gel-phase materials based on G2 exhibited optimum gelation behaviour
      compared to those based on G3(in terms of the thermal strength of the materials).
      Circular dichroism showed that the dendritic effect, programmed in at the
      molecular level, is directly related to the degree of chiral organisation within
      the self-assembled state. The dendritic generation of the peptide controls the
      pattern of amide-amide hydrogen bonding in terms of binding strength and
      alignment as determined using NMR methods. The mode of self-assembly can be
      qualitatively rationalised in terms of an attractive enthalpic interaction (i.e.,
      amide-amide hydrogen bonding), a repulsive interaction (i.e., steric interactions
      between dendritic peptides) and an entropic term related to the hierarchical
      organisation of the gelator building blocks. It is argued that the balance
      between these factors determines the nature of the dendritic effect.

PMID- 15480463
TI  - Synthesis and conjugation of oligosaccharide analogues of fragments of the
      immunoreactive glycan part of the circulating anodic antigen of the parasite
      Schistosoma mansoni.
AB  - The gut-associated circulating anodic antigen (CAA) is one of the major excretory
      antigens produced by the parasite Schistosoma mansoni. The immunoreactive part of
      CAA is a threonine-linked polysaccharide composed of long stretches of the unique
      repeating disaccharide-->6)-[beta-D-GlcpA-(1-->3)]-beta-D-GalpNAc-(1-->.
      Previously, using surface plasmon resonance and ELISA techniques, it has been
      shown that some anti-CAA IgM monoclonal antibodies (MAbs) also recognize members
      of a series of bovine serum albumin (BSA)-coupled synthetic di- to penta
      saccharide fragments of the CAA glycan. To generate information on the molecular
      level about the glycan specificity of the relevant IgM MAbs, two series of
      oligosaccharides related to the CAA disaccharide epitope were synthesized, and
      coupled to BSA. The first three analogues, beta-D-GlcpA-(1-->3)-[small beta]-D
      GlcpNAc-(1-->O), beta-D-GlcpNAc-(1-->6)-[beta-D-GlcpA-(1-->3)]-beta-D-GlcpNAc-(1-
      >O), and beta-D-GlcpA-(1-->3)-beta-D-GlcpNAc-(1-->6)-[beta-D-GlcpA-(1-->3)]-beta
      D-GlcpNAc-(1-->O), wherein the native beta-D-GalpNAc moiety was replaced by beta
      D-GlcpNAc, were synthesized to investigate the specificity of the selected MAbs
      to the carbohydrate backbone of CAA. The second series of analogues, beta-D
      Glcp6S-(1-->3)-beta-D-GalpNAc-(1-->O), beta-D-GalpNAc-(1-->6)-[beta-D-Glcp6S-(1-
      >3)]-beta-D-GalpNAc-(1-->O), and beta-D-Glcp6S-(1-->3)-beta-D-GalpNAc-(1-->6)
      [beta-D-Glcp6S-(1-->3)]-beta-D-GalpNAc-(1-->O), wherein the native beta-D-GlcpA
      moiety was replaced by beta-D-Glcp6S, was synthesized to evaluate the importance
      of the type/nature of the charge of CAA for the MAb recognition.

PMID- 15480464
TI  - Conjugate addition of organocopper reagents to gamma-alkoxybutenolides and
      application to the synthesis of non-racemic alkyl cyclopentenones.
AB  - Simple organocopper reagents are shown to undergo anti-stereoselective 1,4
      addition to menthyloxy-substituted lactone 1 in the presence of BF3.OEt2; the
      Lewis acid causes partial epimerisation of the acetal centre after conjugate
      addition. Enolate alkylation of the adducts leads to di- and trisubstituted
      lactones that are converted, in favourable cases, into di- and trisubstituted
      cyclopentenones.

PMID- 15480465
TI  - Mechanism and structure-reactivity relationships for aromatic hydroxylation by
      cytochrome P450.
AB  - Cytochrome P450 enzymes play a central role in drug metabolism, and models of
      their mechanism could contribute significantly to pharmaceutical research and
      development of new drugs. The mechanism of cytochrome P450 mediated hydroxylation
      of aromatics and the effects of substituents on reactivity have been investigated
      using B3LYP density functional theory computations in a realistic porphyrin model
      system. Two different orientations of substrate approach for addition of Compound
      I to benzene, and also possible subsequent rearrangement pathways have been
      explored. The rate-limiting Compound I addition to an aromatic carbon atom
      proceeds on the doublet potential energy surface via a transition state with
      mixed radical and cationic character. Subsequent formation of epoxide, ketone and
      phenol products is shown to occur with low barriers, especially starting from a
      cation-like rather than a radical-like tetrahedral adduct of Compound I with
      benzene. Effects of ring substituents were explored by calculating the activation
      barriers for Compound I addition in the meta and para-position for a range of
      monosubstituted benzenes and for more complex polysubstituted benzenes. Two
      structure-reactivity relationships including 8 and 10 different substituted
      benzenes have been determined using (i) experimentally derived Hammett sigma
      constants and (ii) a theoretical scale based on bond dissociation energies of
      hydroxyl adducts of the substrates, respectively. In both cases a dual-parameter
      approach that employs a combination of radical and cationic electronic
      descriptors gave good relationships with correlation coefficients R2 of 0.96 and
      0.82, respectively. These relationships can be extended to predict the reactivity
      of other substituted aromatics, and thus can potentially be used in predictive
      drug metabolism models.

PMID- 15480466
TI  - The extraordinary reactions of phenyldimethylsilyllithium with N,N-disubstituted
      amides.
AB  - Phenyldimethylsilyllithium reacts with N,N-dimethylamides in a variety of ways,
      depending upon the stoichiometry, the temperature and, most subtly, on the
      structure of the amide, with quite small-seeming changes in structure leading to
      profound changes in the nature of the products. When equimolar amounts of the
      silyllithium reagent and N,N-dimethylamides 6 are combined in THF at -78 degrees
      C, and the mixture quenched at -78 degrees C, the product is the corresponding
      acylsilane . If the same mixture is warmed to -20 degrees C before quenching, the
      product is a cis enediamine 11. The enediamines are easily isomerised from cis to
      trans, easily oxidised to dienediamines , and, with more difficulty, hydrolysed
      to alpha-aminoketones 13. If two equivalents of the silyllithium reagent are
      used, the product is an alpha-silylamine 20. The mechanism of formation of the
      enediamines appears to be by way of a Brook rearrangement of the tetrahedral
      intermediate 17 followed by loss of a silanoxide ion to give a carbene or carbene
      like species. The 'carbene' combines with the Brook-rearranging nucleophile to
      give an intermediate 28, which loses another silanoxide ion to give the
      enediamine. The same carbene can be attacked by a second equivalent of the
      silyllithium reagent to give the alpha-silylamine 20. Other nucleophiles, like
      alkyllithiums, phenyllithium, and tributylstannyllithium also trap the carbene to
      give products 48-52. The intermediate anions in these reactions, when benzylic,
      can be further trapped with alkylating agents to give the products 33, 34 and 53
      55. In special cases, the anion formed by attack on the carbene can be trapped by
      intramolecular reactions displacing internal leaving groups, as in the formation
      of the enamine 37 and the cyclopentane 41, or attacking a carbonyl group, as in
      the formation of the indanone 61, or attacking a double or triple bond, as in the
      formation of the cyclopentanes 71 and 75. In another special case, the carbene
      reacts with vinyllithium to give an allyllithium intermediate 56, which
      selectively attacks another molecule of carbene to give eventually the gamma
      aminoketone 58. Small changes in the structure of the amide lead to a variety of
      other pathways each of which is discussed in the text. Notably, each member of
      the homologous series of amides Ph(CH2)nCONMe2 gives rise to a substantially
      different product: when n= 0, the reaction is normal, and the yield of the alph]
      silylamine 20e is high; when n=1, proton transfer in the intermediate anion 64
      and displacement of the phenyl group leads to the silaindane 66; when n=2,
      fragmentation of the intermediate anion 80, and capture of the carbene by
      benzyllithium leads to the 1,4-diphenylbut-2-ylamine 83; and when n=3, proton
      transfer in the intermediate anion 67 and displacement of the phenyl group leads
      to the silacyclopentane 69.

PMID- 15480467
TI  - Synthesis of substituted naphthalenes from alpha-tetralones generated by a
      xanthate radical addition-cyclisation sequence.
AB  - A simple, highly efficient and cheap synthesis of substituted naphthalenes is
      reported. These aromatic compounds can be easily prepared in acidic or basic
      conditions from [small alpha]-tetralones, obtained by a xanthate-mediated
      addition-cyclisation sequence.

PMID- 15480468
TI  - Phorboxazole B synthetic studies: construction of C(1-32) and C(33-46)
      subtargets.
AB  - The convergent syntheses of the C(1-32) and C(33-46) domains of phorboxazole B
      are described. An iterative cyclocondensation strategy exploited the Jacobsen
      hetero-Diels-Alder (HDA) reaction as a platform for the synthesis of both the C(5
      9) and C(11-15) tetrahydropyran rings. The use of 2-silyloxydiene coupling
      partners bearing an increasing resemblance to the phorboxazole skeleton was found
      to lead to a reduction in diastereoselectivity, however, in the case of the C(11
      15) ring. The coupling of aldehyde and 2-silyloxydiene by this route provided a
      C(1-32) fragment which was elaborated to the macrolide core of phorboxazole B.
      The synthesis of the C(33-46) domain involved a Nozaki-Kishi coupling of aldehyde
      31 and vinyl iodide 39. The syntheses of 31 and 39 were highly
      diastereoselective: an Evans [Cu(Ph-pybox)](SbF6)2-catalysed Mukaiyama aldol
      reaction formed the cornerstone of the synthesis of 31 whilst a Nagao-Fujita
      acetate aldol reaction provided a convenient means of installing the sole
      stereogenic centre of 39.

PMID- 15480469
TI  - Synthesis of benzothiazoles via ipso substitution of ortho-methoxythiobenzamides.
AB  - An efficient route to the synthesis of benzothiazoles from ortho
      methoxythiobenzamides via the ipso substitution of an aromatic methoxy group is
      presented, and the mechanism of the Jacobson synthesis of benzothiazoles is
      further investigated.

PMID- 15480470
TI  - Cu(I)-carbenoid- and Ag(I)-Lewis acid-catalyzed asymmetric intermolecular
      insertion of alpha-diazo compounds into N-H bonds.
AB  - Chiral Cu(I)-bisoxazoline- and Cu(I)-PN-complexes were found to catalyze the
      intermolecular insertion of alpha-diazo compounds into N-H bonds. The insertion
      reactions proceed with enantioselectivities of up to 28% ee for the different
      alpha-diazo acetates into one of the N-H bonds of different amines. Analogous
      chiral Ag(I) complexes were found to give higher enantioselectivities of up to
      48% ee, however, lower yields were obtained. There are indications, that the
      Ag(I)-mediated reactions follow a different reaction mechanism compared to the
      Cu(I)-catalyzed insertions. It is demonstrated that different alpha-amino acid
      derivatives can be obtained via this approach in good yields and with low to
      moderate enantioselectivities. However, the results obtained are the highest
      asymmetric inductions obtained for an intermolecular N-H insertion via chiral
      carbene complexes or chiral Lewis acid catalysis.

PMID- 15480471
TI  - Research applications of the Cambridge Structural Database (CSD).
AB  - Crystal structure data are of fundamental importance in a wide spectrum of
      scientific activities. This tutorial review summarises the principal application
      areas, so far, for the data from more than 300,000 crystal structures of small
      organic and metal-organic compounds that are stored in the Cambridge Structural
      Database (CSD). Direct use of the accumulated data is valuable in establishing
      standard molecular dimensions, determining conformational preferences and in the
      study of intermolecular interactions, all of which are crucial in structural
      chemistry and rational drug design. More recently, information derived from the
      CSD has been used to construct two dynamic libraries of structural knowledge:
      Mogul, which stores intramolecular information, and IsoStar, which stores
      information about intermolecular interactions. These electronic libraries provide
      information "at the touch of a button". In their turn, the libraries also serve
      as sources of structural knowledge for applications software that address
      specific problems in small-molecule and biological chemistry.

PMID- 15480472
TI  - Developments in inorganic crystal engineering.
AB  - The design and synthesis of crystalline materials through the self-assembly of
      molecular building blocks and the pursuit of functional materials based upon this
      approach are usually classified under the banner Crystal Engineering. The field
      is interdisciplinary in nature involving synthetic, materials, structural and
      theoretical chemists. There are strong ties to modern crystallography which can
      offer rapid and accurate structure determination and, in particular, insight into
      molecular and intermolecular geometries. Illustrative examples that chart the
      development field and provide an assessment of the current state of the art will
      be reviewed with an emphasis on inorganic chemistry. Broadly speaking, two
      classes of compounds will be discussed: those based upon molecules or ions linked
      into networks via noncovalent interactions and those (coordination polymers) in
      which metal centres are linked using coordination bonds through bridging ligands
      into extended networks.

PMID- 15480473
TI  - Low temperature single crystal X-ray diffraction: advantages, instrumentation and
      applications.
AB  - The benefits of carrying out single crystal X-ray diffraction (SXRD) experiments
      at low temperatures have long been recognised by the scientific community, as
      clearly demonstrated by the massive increase in publications reporting the use of
      low temperature SXRD in the past 15 years. This tutorial review will summarise
      the advantages, many of them now often forgotten by its practitioners or never
      known by the newcomers to the field, of performing single crystal X-ray
      diffraction experiments at low temperatures. The instrumentation currently
      available to university laboratories, which has been greatly improved over the
      past 5 years, will also be briefly described and a few different examples
      covering a range of applications will be presented.

PMID- 15480474
TI  - Single-crystal X-ray diffraction studies of photo-induced molecular species.
AB  - This tutorial review gathers together the recent developments in single-crystal X
      ray diffraction that are starting to enable one to quantify directly the nature
      of light-induced electronic perturbations in chemical structures. Such structural
      information is key to understanding many photo-activated chemical processes and
      physical properties, and a description of the scientific impetus behind this
      incipient area of structural science, from academic and industrial perspectives,
      is given. Photoisomerism processes, solid-state photochemical reactions and spin
      cross-over magnetic transitions, that have long-lived or irreversible light
      induced states, are best understood by unravelling their three-dimensional
      structures measured in situ in their photo-converted state. A review of steady
      state laser-induced single-crystal X-ray diffraction studies conducted, to date,
      and the experimental methodologies used in order to realise such structures, is
      presented. The structural characterisation of more transient photo-induced
      species (down to picosecond lifetimes) is paramount to a better understanding of
      the materials that undergo high-speed electronic switching, which make operative
      much of the electronics and optics industry, since there exists an inherent
      relationship between the excited-state structure and the physical properties
      exhibited. Prime examples include excited-state structures of molecular
      conductors and luminescent materials with potential applications as molecular
      wires, light-emitting diodes, non-linear optics, triboluminescence and
      electroluminescence. Previously, only indirect and qualitative interpretations of
      the nature of these excited-states could be formulated via spectroscopic
      techniques, but the developments in ms-ps time-resolved laser pump, X-ray probe
      single-crystal diffraction techniques, described herein, are overcoming this
      barrier, affording results that are entirely quantitative via a three-dimensional
      structural representation. In this regard, a review of structures of transient
      species studied to date is presented along with a discussion of the key
      experimental parameters that are required for a successful experiment, in terms
      of the X-ray, laser and sample characteristics. The importance of auxiliary
      spectroscopic work and complementary theoretical calculations is also briefly
      discussed. The paper concludes with a future outlook on new possible X-ray
      sources that will facilitate such work and extend it to structural studies on
      even more ephemeral species in the future.

PMID- 15480475
TI  - Polarimetric imaging of crystals.
AB  - Classical crystal optics has recently undergone a renaissance as developments in
      optical microscopy and polarimetry, enabled in part by sensitive imaging CCD
      cameras and personal computers, now permit the analytical separation of various
      optical effects that are otherwise convolved in polarized light micrographs. In
      this tutorial review, we review recent developments in the measurement of the
      principal crystallo-optical quantities including linear birefringence, linear
      dichroism, circular birefringence, and circular dichroism, as well as new effects
      in crystal optics encountered in unusual mixed crystals. The new microscopies and
      polarimetries are applied to problems of crystallographic twinning, phase
      transformations, stress birefringence, symmetry reduction, and the design of new
      crystalline materials.

PMID- 15480476
TI  - How to determine structures when single crystals cannot be grown: opportunities
      for structure determination of molecular materials using powder diffraction data.
AB  - Many crystalline solids cannot be prepared as single crystals of sufficient size
      and/or quality for structure determination to be carried out using single crystal
      X-ray diffraction techniques. In such cases, when only polycrystalline powders of
      a material are available, it is necessary instead to tackle structure
      determination using powder X-ray diffraction. This article highlights recent
      developments in the opportunities for determining crystal structures directly
      from powder diffraction data, focusing on the case of molecular solids and giving
      particular attention to the most challenging stage of the structure determination
      process, namely the structure solution stage. In particular, the direct-space
      strategy for structure solution is highlighted, as this approach has opened up
      new opportunities for the structure determination of molecular solids. The
      article gives an overview of the current state-of-the-art in structure
      determination of molecular solids from powder diffraction data. Relevant
      fundamental aspects of the techniques in this field are described, and examples
      are given to highlight the application of these techniques to determine crystal
      structures of molecular materials.

PMID- 15480477
TI  - Beyond classical applications of powder diffraction.
AB  - This article provides a short tutorial review of how laboratory powder
      diffraction methods can be used to establish a variety of "non-traditional"
      pieces of information about solid state materials-information beyond simple phase
      identification or structure determination at a specific temperature. The examples
      show how unique insights into synthetic pathways, reaction mechanisms, reaction
      kinetics, polymorphism, phase transitions and physical properties can be obtained
      for a variety of different types of materials.

PMID- 15480478
TI  - Synchrotron and neutron techniques in biological crystallography.
AB  - Synchrotron radiation (SR) techniques are continuously pushing the frontiers of
      wavelength range usage, smaller crystal sample size, larger protein molecular
      weight and complexity, as well as better diffraction resolution. The new research
      specialism of probing functional states directly in crystals, via time-resolved
      Laue and freeze trapping structural studies, has been developed, with a range of
      examples, based on research stretching over some 20 years. Overall, SR X-ray
      biological crystallography is complemented by neutron protein crystallographic
      studies aimed at cases where much more complete hydrogen details are needed
      involving synergistic developments between SR and neutron Laue methods. A big new
      potential exists in harnessing genome databases for targeting of new proteins for
      structural study. Structural examples in this tutorial review illustrate new
      chemistry learnt from biological macromolecules.

PMID- 15480479
TI  - High-throughput protein crystallography and drug discovery.
AB  - Single crystal X-ray diffraction is the technique of choice for studying the
      interactions of small organic molecules with proteins by determining their three
      dimensional structures; however the requirement for highly purified protein and
      lack of process automation have traditionally limited its use in this field.
      Despite these shortcomings, the use of crystal structures of therapeutically
      relevant drug targets in pharmaceutical research has increased significantly over
      the last decade. The application of structure-based drug design has resulted in
      several marketed drugs and is now an established discipline in most
      pharmaceutical companies. Furthermore, the recently published full genome
      sequences of Homo sapiens and a number of micro-organisms have provided a
      plethora of new potential drug targets that could be utilised in structure-based
      drug design programs. In order to take maximum advantage of this explosion of
      information, techniques have been developed to automate and speed up the various
      procedures required to obtain protein crystals of suitable quality, to collect
      and process the raw X-ray diffraction data into usable structural information,
      and to use three-dimensional protein structure as a basis for drug discovery and
      lead optimisation. This tutorial review covers the various technologies involved
      in the process pipeline for high-throughput protein crystallography as it is
      currently being applied to drug discovery. It is aimed at synthetic and
      computational chemists, as well as structural biologists, in both academia and
      industry, who are interested in structure-based drug design.

PMID- 15480480
TI  - Antibacterial photodynamic therapy in dermatology.
AB  - Photodynamic therapy (PDT) appears to be endowed with several favourable features
      for the treatment of localized microbial infections, especially after the advent
      of cationic photosensitising agents (phenothiazines, meso-substituted porphyrins,
      polylysine-bound chlorins) which properly interact with the outer wall at the
      surface of several types of bacterial and yeast cells, increase their
      permeability, and allow significant amounts of photosensitizer to be accumulated
      at the level of the cytoplasmic membrane. These photosensitisers are
      characterized by a broad spectrum of activity, being effective toward both wild
      strain and antibiotic-resistant gram-positive and gram-negative bacteria and
      yeasts. In general, extensive eradication of pathogens can be achieved under mild
      irradiation conditions, such as short incubation times and low fluence-rates,
      which guarantees a high degree of selectivity in comparison with the main
      constituents of host tissues, such as keratinocytes and fibroblasts. Moreover,
      the photosensitised inactivation of microorganisms is typically a multi-target
      process; as a consequence, the selection of photoresistant microbial strains is
      very unlikely and has not been experimentally observed so far. Possible initial
      targets of antimicrobial PDT applications include periodontal diseases, impetigo,
      atopic dermatitis, acne vulgaris, infected wounds, and superinfected posriatic
      plaques.

PMID- 15480481
TI  - An alternative ionic liquid based electrolyte for dye-sensitized solar cells.
AB  - An ionic liquid based, environmentally friendly electrolyte LiI(C(2)H(5)OH)(4)
      I(2) was used as the electrolyte to fabricate dye-sensitized solar cells (DSSC)
      with energy conversion efficiency of 4.9% under AM 1.5 (100 mW cm(-2))
      irradiation.

PMID- 15480482
TI  - Autofluorescence properties of isolated rat hepatocytes under different metabolic
      conditions.
AB  - The contribution of endogenous fluorophores - such as proteins, bound and free
      NAD(P)H, flavins, vitamin A, arachidonic acid - to the liver autofluorescence was
      studied on tissue homogenate extracts and on isolated hepatocytes by means of
      spectrofluorometric analysis. Autofluorescence spectral analysis was then applied
      to investigate the response of single living hepatocytes to experimental
      conditions resembling the various phases of the organ transplantation. The
      following conditions were considered: 1 h after cells isolation (reference
      condition); cold hypoxia; rewarming-reoxygenation after cold preservation. The
      main alterations occurred for NAD(P)H and flavins, the coenzymes strictly
      involved in energetic metabolism. During cold hypoxia NAD(P)H, mainly the bound
      form, showed an increase followed by a slow decrease, in agreement with the
      inability of the respiratory chain to reoxidize the coenzyme, and a subsequent
      NADH reoxidation through alternative anaerobic metabolic pathways. Both
      bound/free NAD(P)H and total NAD(P)H/flavin ratio values were altered during cold
      hypoxia, but approached the reference condition values after rewarming
      reoxygenation, indicating the cells capability to restore the basal redox
      equilibrium. A decrease of arachidonic acid and vitamin A contributions occurred
      after cold hypoxia: in the former case it may depend on the balance between
      deacylation and reacylation of fatty acids, in the latter it might be related to
      the vitamin A antioxidant role. An influence of physico-chemical status and
      microenvironment on the fluorescence efficiency of these fluorophores cannot be
      excluded. In general, all the changes observed for cell autofluorescence
      properties were consistent with the complex metabolic pathways providing for
      energy supply.

PMID- 15480483
TI  - The stereoselectivity of the Paterno-Buchi reaction between tertiary 2
      furylmethanol derivatives and aromatic carbonyl compounds: on the nature of the
      hydroxy directing effect.
AB  - The photochemical reaction of 1-(2-furyl)-1-phenylethanol with benzaldehyde gave
      a mixture of regioisomeric products. The adduct obtained on the more hindered
      side of the molecule was obtained with complete diastereoselectivity. The same
      substrate with benzophenone gave only one product with a diastereoisomeric excess
      of 48%. The reaction of 2-(2-furyl)-3,3-dimethylbutan-2-ol with benzaldehyde and
      benzophenone gave the corresponding adducts on the more hindered side of the
      molecule with diastereoisomeric excesses of 42 and 71%, respectively. These
      results, and also those obtained using 2-furylphenylmethanol with benzophenone
      and acetone (complete diastereoselectivity and absence of diastereoselectivity,
      respectively), were explained assuming the attack of the excited carbonyl
      compound on the same side as the hydroxy group, through the formation of a
      hydrogen bond or of a complex. This type of attack gave the biradical
      intermediate in preferential conformations. The relative energies of these
      conformers account for the observed diastereoselectivity.

PMID- 15480484
TI  - Photoreactions of p-benzo-, p-naphtho- and p-anthraquinones with ascorbic acid.
AB  - The photoreduction of 1,4-benzoquinone (BQ), 1,4-naphthoquinone (NQ), 9,10
      anthraquinone (AQ) and several derivatives, e.g. dimethylBQ, trimethylBQ,
      duroquinone, bromoNQ, methoxyNQ, methylAQ and dimethylAQ in acetonitrile-water by
      ascorbate was studied by time-resolved UV-vis spectroscopy using 20 ns laser
      pulses at 308 nm and continuous 254 nm irradiation. The semiquinone radical
      (*QH/Q*(-)) is formed after H-atom transfer from ascorbate to the quinone triplet
      state. The rate constant for quenching is k(q)=(2-9) x 10(9) M(-1) s(-1).
      Termination of the radicals takes place in the micros-ms range. The results are
      compared with those initiated by electron transfer from DABCO under similar
      conditions, where the k(q) values are similar, but the termination of Q*(-) takes
      place by electron back transfer not yielding hydroquinones. Specific properties
      of the quinone triplet state, e.g. self-quenching, nucleophilic water addition
      and the effects of structure are discussed.

PMID- 15480485
TI  - Structural modelling of optical and electrochemical properties of 4
      aminodiphenylamines - optoelectronic studies on a polyaniline repeating unit.
AB  - Amino-diphenylanilines and their planarized and twisted model compounds have been
      investigated by steady state and time-resolved absorption and emission, as well
      as by spectroelectrochemistry. These polyaniline model compounds show that the
      observation of excited states with full charge separation is linked to molecular
      twisting where the diaminobenzene is the donor and the phenyl group the acceptor.
      The observable charge transfer fluorescence shows the characteristic features of
      twisted intramolecular charge transfer (TICT) excited states, i.e. forbidden
      emissive properties and strong solvatochromic red shift. The transient absorption
      spectrum of the TICT state matches the ground state absorption spectrum of the
      electrochemically produced radical cation of the molecule. This is the first
      example where excited-state properties of the neutral and ground state properties
      of the radical cation are directly linked.

PMID- 15480486
TI  - Tunable fluorescence emission in pyrene-(2,2'-bipyridine) dyads containing
      phenylene-ethynylene bridges.
AB  - A synthetic route is described for the preparation of a series of pyrene
      containing pi-conjugated 2,2'-bipyridine (bpy) ligands. These compounds have been
      investigated by steady-state and time-resolved fluorescence spectroscopy. They
      display intense visible absorption and fluorescence emission properties that can
      be very efficiently modulated by the complexation of zinc(ii) metal ions to the
      bpy coordinating unit. The solvatochromism of the emission band of the zinc(ii)
      complexes, the fluorescence quantum yields, and lifetimes in THF have been
      determined. Zinc(ii)-induced formation of a charge transfer singlet excited
      states induces an increase in dipole moment of more than 20 D. Semiempirical
      theoretical calculations were performed and allowed to assess the electronic
      nature of ground and excited states of the free ligands and and that of the
      corresponding zinc(ii) complexes.

PMID- 15480487
TI  - The deactivation pathways of the excited-states of the mycosporine-like amino
      acids shinorine and porphyra-334 in aqueous solution.
AB  - In vitro studies on the structurally related mycosporine-like amino acids (MAAs)
      porphyra-334 and shinorine in aqueous solutions were carried out aiming at their
      full photochemical and photophysical characterization and expanding the evidence
      on the assigned UV-photoprotective role of the molecules in vivo. The experiments
      on shinorine confirmed a high photostability and a poor fluorescence quantum
      yield, in concordance with previous results on porphyra-334. The estimation of
      triplet production quantum yields for both MAAs was achieved by laser-flash
      photolysis measurements. In particular, photosensitization experiments on
      porphyra-334 support the participation of the triplet state in the
      photodecomposition mechanism yielding a more precise value of [capital Phi](T).
      As well, photoacoustic calorimetry experiments allowed the first direct
      quantification of the nonradiative relaxation pathways of the excited MAAs in
      solution, corroborating that the vast majority (ca. 97%) of the absorbed energy
      is promptly delivered to the surroundings as heat, consistently with the low
      photodecomposition and emission yields observed.

PMID- 15480488
TI  - The cyclobutane dimers of 5-methylcytosine and their deamination products.
AB  - The photochemical reactions of 5-methylcytosine (m(5)C), a minor component of
      mammalian DNA, have been studied at a concentration of 2 mM in frozen 10 mM
      aqueous NaCl solution at dry ice temperature (194.5 K). For these studies, low
      pressure lamps emitting mainly UVB radiation were used. We have isolated and
      characterized three cyclobutane dimers, namely the cis-anti(c,a) the cis-syn(c,s)
      and the trans-syn(t,s) forms. While the c,a and the t,s cyclobutane dimers are
      relatively stable towards deamination upon standing in solution at 277 K, the c,s
      isomer is gradually converted into the corresponding c,s m(5)C-thymine (Thy)
      mixed dimer; this latter reaction occurs considerably faster at 310 K. The t,s
      cyclobutane dimer is converted into the corresponding m(5)C-Thy mixed dimer upon
      incubation at 373 K, while the c,a dimer is converted into a mixture of m(5)C and
      c,a mixed dimer when incubated at 310 K. Irradiation of equimolar mixtures of Thy
      (1 mM) and m(5)C (1 mM) under similar conditions yields each of the three m(5)C
      cyclobutane dimers, as well as significant amounts of c,a, c,s and t,s m(5)C-Thy
      mixed cyclobutane dimers. These m(5)C-Thy dimers undergo decompositions similar
      in nature to the processes undergone by m(5)C cyclobutane dimers. Pseudo-first
      order rate constants for deamination of the c,s m(5)C homodimer and c,s m(5)C-Thy
      heterodimer at various temperatures and at pH 7.7 have been measured and the
      enthalpies and entropies of activation have been evaluated for the deamination
      processes for these two compounds. The two dimers have half-lives of about 14 and
      22 h, respectively, at 310 K; however, at 273 K, the corresponding half-lives can
      be evaluated as being around 30 and 36 days, respectively.

PMID- 15480489
TI  - Polychlorinated biphenyls in preserved human umbilical cords.
AB  - Congener-specific PCB analyses were carried out on preserved umbilical cord
      samples. Total PCB concentrations were higher in the umbilical cords of subjects
      born in the 1960s and 70s than in those born more recently. Total PCB
      concentrations in the cords from 3 groups of siblings showed no linear
      relationships between birth order and total PCB concentration. The congener and
      homologue compositions of PCBs in the umbilical cords of one group of siblings
      were similar to those of commercial PCB products.

PMID- 15480490
TI  - Synchrotron X-ray fluorescence and trace metals in the cementum rings of human
      teeth.
AB  - Synchrotron micro X-ray fluorescence has been used to study differences in the
      trace element concentration between the dentine and cementum rings of human
      teeth. The results show that metals such as zinc are concentrated in the cementum
      rings. This suggests that if the rings are deposited annually a temporal record
      of metal exposure may be extracted from this material.

PMID- 15480491
TI  - Speciation of nickel in Canadian subbituminous and bituminous feed coals, and
      their ash by-products.
AB  - The nickel species in the feed coals and ash by-products from seven Canadian
      power plants (including one with a fluidized bed combuster) burning local
      subbituminous and bituminous coals with sulfur contents ranging from 0.22 to 3.6%
      have been examined using nickel XANES spectroscopy. XANES spectroscopy of Ni in
      coal and coal derived ash is complicated by a poor signal : noise ratio due to
      fluorescence of the much more abundant iron in the coal. Nevertheless, it has
      proved possible to show that the Ni environment in coals varies from largely
      oxidic species to mixtures of Ni-containing oxide and sulfide species. The nickel
      in one oxidized coal appears to be present as nickel sulfate. Nickel in all
      bottom and fly ash samples examined appears also to be present largely in oxygen
      anion environments. With the exception of one fly ash sample, for which the Ni
      exhibited spectral features similar to those for Ni(2+) in spinel or oxide
      phases, the nickel in the bottom and fly ash samples appears to exist largely as
      Ni(2+) in environments similar to those reported for Ni in silicate glasses. The
      data obtained indicate that the presence of potentially carcinogenic nickel
      sulfides in ash by-products from combustion of these coals is unlikely.

PMID- 15480492
TI  - Speciation and mass-balance of mercury from pulverized coal fired power plants
      burning western Canadian subbituminous coals.
AB  - This report summarizes the results of a study carried out on six pulverized coal
      fired power plants in western Canada burning subbituminous coal for the mass
      balance and speciation of mercury. The main objectives of this study were to:
      determine the total gaseous mercury (TGM) emitted from stacks of power plants
      using the Ontario Hydro method; identify the speciation of emitted mercury such
      as metallic (Hg(0)) and gaseous elemental (GEM) mercury; and perform mass-balance
      calculations of mercury for milled-coal, bottom ash, electrostatic precipitators
      (ESP) fly ash and stack-emitted mercury based on three tests. Sampling of mercury
      was carried out using the Ontario Hydro method and mercury was determined using
      the USEPA method 7473 by cold vapor atomic absorption (CVAAS). The sample
      collection efficiencies confirmed that both oxidized and the elemental mercury
      had been successfully sampled at all power plants. The total gaseous mercury
      emitted (TGM) is 6.95-15.66 g h(-1) and is mostly in gaseous elemental mercury
      (GEM, Hg(0)) form. The gaseous elemental mercury is emitted at a rate of 6.59
      12.62 g h(-1). Reactive gaseous mercury (RGM, Hg(2+)) is emitted at a rate of
      0.34-3.68 g h(-1). The rate of emission of particulate mercury (Hg(p)) is low and
      is in the range 0.005-0.076 g h(-1). The range of mass-balances for each power
      plant is more similar to the variability in measured mercury emissions, than to
      the coal and ash analyses or process data. The mass-balance calculations for the
      six power plants, performed on results of the three tests at each power plant,
      are between 86% and 123%, which is acceptable and within the range 70-130%. The
      variation in mass-balance of mercury for the six power plants is mostly related
      to the variability of coal feed rate.

PMID- 15480493
TI  - Submicrometer elemental carbon as a selective measure of diesel particulate
      matter in coal mines.
AB  - A monitoring method for diesel particulate matter was published as Method 5040 by
      the National Institute for Occupational Safety and Health (NIOSH). Organic and
      elemental carbon are determined by the method, but elemental carbon (EC) is a
      better exposure measure. The US Mine Safety and Health Administration (MSHA)
      proposed use of NIOSH 5040 for compliance determinations in metal and nonmetal
      mines. MSHA also published a rulemaking for coal mines, but no exposure standard
      was provided. A standard based on particulate carbon is not considered practical
      because of coal dust interference. Interference may not be a problem if an
      appropriate size-selective sampler and EC exposure standard are employed.
      Submicrometer dust concentrations found in previous surveys of nondieselized,
      underground coal mines were relatively low. If a large fraction of the
      submicrometer dust is organic and mineral matter, submicrometer EC concentrations
      would be much lower than submicrometer mass concentrations. Laboratory and field
      results reported herein indicate the amount of EC contributed by submicrometer
      coal dust is minor. In a laboratory test, a submicrometer EC concentration of 31
      microg m(-3) was found when sampling a respirable coal dust concentration over
      three times the US compliance limit (2 mg m(-3)). Laboratory results are
      consistent with surveys of nondieselized coal mines, where EC results ranged from
      below the method limit of detection to 18 microg m(-3) when size-selective
      samplers were used to collect dust fractions having particle diameters below 1.5
      microm-submicrometer EC concentrations were approximate 7 microg m(-3). In
      dieselized mines, submicrometer EC concentrations are much higher.

PMID- 15480494
TI  - Indoor and outdoor air concentrations of BTEX and NO2: correlation of repeated
      measurements.
AB  - Studies on health effects of air pollutants ideally define exposure through the
      collection of air samples in the participants' homes. Concentrations derived from
      these samples are then considered as an estimate for the average concentration of
      air pollutants in the homes. Conclusions drawn from such studies therefore depend
      very much on the validity of the measured air pollution concentrations. In this
      paper we analysed repeated BTEX and NO(2) measurements with a time period of
      several months lying between the two conducted home visits. We investigated the
      variability of their concentrations over time by determining correlation
      coefficients and calculating within- and between-home variances. Our population
      consisted of 631 homes of participants from two cohort studies within the
      framework of the German study on Indoor Factors and Genetics in Asthma. Air
      pollutants were measured using passive samplers both indoors and outdoors. The
      measured BTEX concentrations were poorly correlated, with Pearson's correlation
      coefficient r ranging from -0.19 to 0.27. Additionally, a considerable seasonal
      effect could be observed. A higher correlation was found for the NO(2)
      concentrations with r ranging between 0.24 and 0.55. For the BTEX, the between
      home variance was bigger than the within-home variance, for NO(2) both variances
      were of about the same order. Our results indicate that in a setting of moderate
      climate like in Germany, the variability of BTEX and NO(2) concentrations over
      time is high and a single measurement is a poor surrogate for the long-term
      concentrations of these air pollutants.

PMID- 15480495
TI  - Characterization and source identification of airborne trace metals in Singapore.
AB  - Airborne particulate trace metals have important health implications. As a
      consequence, their concentrations are increasingly monitored in many urban
      locations worldwide. In this study, fine atmospheric particles (PM(2.5)) were
      collected in Singapore over a period of 83 consecutive days during 2000, and
      analysed to determine the concentration of trace elements using ICP-MS.
      Altogether, eighteen airborne trace metals were quantified: Al, Ag, Ba, Cd, Cr,
      Co, Cu, Fe, Ga, Li, Mn, Ni, Pb, Sr, Zn, V, Si, and Ti. While Li was the least
      abundant trace metal with a mean concentration of 0.2 ng m(-3), Zn showed the
      maximum mean concentration of 279.1 ng m(-3). Calculation of enrichment factors
      indicated that the elements Pb, Zn, Cd, V, Ni, Cr, and Cu were enriched by
      factors of 30 to 5000 relative to their natural abundance in crustal soil. The
      extent of metal pollution in the study area was assessed by comparing the
      measured concentrations to those reported in the literature for a selected number
      of urban sites in other parts of the world. Factor analysis was used to identify
      the major sources affecting particulate air pollution in Singapore. The sources
      that contribute to the loading of trace metal-bearing aerosols in the Singapore
      urban atmosphere include fuel oil-fired power plants, metal processing industry,
      land reclamation and construction activities, municipal solid waste incinerators,
      and traffic emissions.

PMID- 15480496
TI  - A comparison of X-ray fluorescence and wet chemical analysis of air filter
      samples from a scrap lead smelting operation.
AB  - Personal and area air samples were taken at a scrap lead smelter operation in a
      bullet manufacturing facility. Samples were taken using the 37-mm styrene
      acrylonitrile closed-face filter cassette (CFC, the current US standard device
      for lead sampling), the 37-mm GSP or "cone" sampler, the 25-mm Institute of
      Occupational Medicine (IOM) inhalable sampler, and the 25-mm Button sampler
      (developed at the University of Cincinnati). Polyvinylchloride filters were used
      for sampling. The filters were pre- and post-weighed, and analyzed for lead
      content using a field-portable X-ray fluorescence (XRF) analyzer. The filters
      were then extracted with dilute nitric acid in an ultrasonic extraction bath and
      the solutions were analyzed by inductively coupled plasma optical emission
      spectroscopy. The 25-mm filters were analyzed using a single XRF reading, while
      three readings on different parts of the filter were taken from the 37-mm
      filters. The single reading from the 25-mm filters was adjusted for the nominal
      area of the filter to obtain the mass loading, while the three readings from the
      37-mm filters were inserted into two different algorithms for calculating the
      mass loadings, and the algorithms were compared. The IOM sampler was designed for
      material collected in the body of the sampler to be part of the collected sample
      as well as that on the filter. Therefore, the IOM sampler cassettes were rinsed
      separately to determine if wall-loss corrections were necessary. All four
      samplers gave very good correlations between the two analytical methods above the
      limit of detection of the XRF procedure. The limit of detection for the 25-mm
      filters (5 microg) was lower than for the 37-mm filters (10 microg). The
      percentage of XRF results that were within 25% of the corresponding ICP results
      was evaluated. In addition, the bias from linear regression was estimated. Linear
      regression for the Button sampler and the IOM sampler using single readings and
      the GSP using all tested techniques for total filter loading gave acceptable XRF
      readings at loadings equivalent to sampling at the OSHA 8-hour Action Level and
      Permissible Exposure Limit. However, the CFC only had acceptable results when the
      center reading corrected for filter area was used, which was surprising, and may
      be a result of a limited data set. In addition to linear regression, simple
      estimation of bias indicated reasonable agreements between XRF and ICP results
      for single XRF readings on the Button sampler filters, (82% of the individual
      results within criterion), and on the IOM sampler filters (77% or 61%--see text),
      and on the GSP sampler filters using the OSHA algorithm (78%). As a result of
      this pilot project, all three samplers were considered suitable for inclusion in
      further field research studies.

PMID- 15480497
TI  - Total versus inhalable sampler comparison study for the determination of asphalt
      fume exposures within the road paving industry.
AB  - Exposure to asphalt fumes has a threshold limit value (TLV of 0.5 mg m(-3)
      (benzene extractable inhalable particulate) as recommended by the American
      Conference of Governmental Industrial Hygienists (ACGIH). This reflects a recent
      change (2000) whereby two variables are different from the previous
      recommendation. First is a 10-fold reduction in quantity from 5 mg m(-3) to 0.5
      mg m(-3). Secondly, the new TLV specifies the "inhalable" fraction as compared to
      what is presumed to be total particulate. To assess the impact of these changes,
      this study compares the differences between measurements of paving asphalt fume
      exposure in the field using an "inhalable" instrument versus the historically
      used 'total' sampler. Particle size is also examined to assist in the
      understanding of the aerodynamic collection differences as related to asphalt
      fumes and confounders. Results show that when exposures are limited to asphalt
      fumes, a 1:1 relationship exists between samplers, showing no statistically
      significant differences in benzene soluble matter (BSM). This means that for the
      asphalt fume ACGIH TLV, the 'total' 37-mm sampler is an equivalent method to the
      "inhalable" method, referred to as IOM (Institute of Occupational Medicine), and
      should be acceptable for use against the TLV. However, the study found that when
      confounders (dust or old asphalt millings) are present in the workplace, there
      can be significant differences between the two samplers' reported exposure. The
      ratio of IOM/Total was 1.37 for milling asphalt sites, 1.41 for asphalt paving
      over granular base, and 1.02 for asphalt over asphalt pavements.

PMID- 15480498
TI  - Investigation of the aerosol structure over an urban area using a polarization
      lidar.
AB  - The paper presents a lidar study of the aerosol structure in the planetary
      boundary layer in the case of radiation fog and haze. A conceptual model of the
      dynamics of the depolarization coefficient profile during the mixing layer
      development, taking into account the presence of a multilayered inversions and
      radiation fogs, is proposed. Various techniques are employed in the processing of
      the lidar signal in order to determine the mixing layer height as well as more
      details of the aerosol structure in the low atmosphere, namely, finding the
      maximum of the signal returned from the lowest temperature inversion, the
      crossing point of the S function's first derivative with the x axis, and profiles
      of the depolarization ratio. After the complete destruction of the stable
      stratification, a low constant value of the depolarization ratio within the newly
      formed mixing layer is being observed. The study of stable boundary layer
      disintegration and convective boundary layer formation in the presence of fogs
      and/or clouds is of both scientific and practical significance in what concerns
      the protection of the environment and the aviation meteorology.

PMID- 15480499
TI  - Towards a holistic approach for the urban environment and its impact on energy
      utilisation in buildings: the ATREUS project.
AB  - Enhanced urbanisation and its impact on the urban climate have a significant
      impact on the energy behaviour of buildings. Rising standards in indoor
      environmental quality lead to higher energy consumption values for heating,
      ventilation and air-conditioning purposes. ATREUS is a research and training
      network launched recently aiming to cover some of these aspects to enable a
      better understanding of the phenomena as well as providing high quality training
      for young European researchers. Having completed one year of work, some
      indicative results of the approach used within ATREUS have already produced both
      methodological approaches and combinatorial case studies; an example of the
      latter, based on the Thessaloniki experiment and the results produced by an
      extended field survey, will be discussed.

PMID- 15480500
TI  - Outcomes of the first round of local authority air quality Review and Assessments
      under the UK's air quality strategy.
AB  - In 1997, the UK government instigated the practice of Local Air Quality
      Management (LAQM) in the UK. This process is based on local authorities
      undertaking Review and Assessments of air quality within their areas. The first
      round of Review and Assessments have now been completed and represents the most
      extensive and coordinated analysis of air pollution ever undertaken in the UK,
      and probably in Europe. This paper takes a broad look at the outcomes of this
      process so far and identifies some of the key areas where lessons have/can be
      learnt both about patterns of air pollution in the UK and about the framework for
      investigating these that has been implemented under the LAQM regime. The process
      has led to a much higher number of local authorities finding problems with air
      pollution than initially expected. It has also challenged many assumptions about
      the significance of various pollutants and their sources.

PMID- 15480501
TI  - [How much CT does PET/CT need?].

PMID- 15480502
TI  - Limitations of dual time point FDG-PET imaging in the evaluation of focal
      abdominal lesions.
AB  - AIM: For the evaluation of the diagnostic potential of dual time point FDG
      positron emission tomography (PET) in patients with suspicious focal abdominal
      uptake, dual time point PET imaging was compared with clinical findings.
      PATIENTS, METHODS: In a prospective study, 56 patients exhibiting a solitary
      suspicious, intense abdominal FDG uptake, underwent dual time point PET imaging
      for staging or restaging of different malignant tumors, maximal standardized
      uptake value (SUVmax) measurements included. The first acquisition was started
      64.8 +/- 19.5, the second 211.3 +/- 52.5 min after FDG injection. The final
      diagnosis based on CT or MRT imaging and a follow-up period of 12.6 +/- 2.8
      months. Additionally, colonoscopy was done in 6 patients. In another 6 patients
      histopathology was obtained from CT guided biopsy. RESULTS: Malignant focal
      abdominal lesions with a SUVmax <2.5 (n = 4) showed an uptake increase of > or
      =30%. In the remaining malignant cases with an uptake of > or =2.5 (n = 11),
      uptake increased in 64% and decreased in 36%. Malignant lesions showing FDG
      uptake decrease (n = 4) had an initial SUVmax value > or =2.5 and remained with a
      SUVmax > or =2.5 in the second imaging. In benign lesions with an initial SUVmax
      > or =2.5 (n = 31), the uptake increased in 17 patients (55%) and decreased in 14
      patients (45%). All lesions which changed configuration (33%) were confirmed as
      benign (n = 5). CONCLUSION: Using dual time point PET abdominal lesions show a
      very hetergenous uptake pattern regardless of their dignity. Malignancy can only
      be reliably excluded in lesions which change their configuration and in lesions
      with an initial SUVmax value <2.5 combined with an SUV decrease in the delayed
      imaging. Particularly abdominal lesions which show an initial SUVmax > or =2.5
      combined with a SUV increase in the delayed imaging are suspicious for malignancy
      and need further clarification.

PMID- 15480503
TI  - Reduction of the LVEF measured with gSPECT after 1-3 hours after physical
      exercise in CAD.
AB  - AIM: It has been shown that exercise may lead to the myocardial stunning with
      reduction of LVEF, persisting for some time despite recovery of perfusion. The
      aim of this study was to check whether the post-stress decrease of LVEF lasts as
      long as 3 h after exercise. PATIENTS, METHODS: The study was performed in 46
      patients with CAD and in 10 normals (NMS). All patients underwent myocardial
      gSPECT after (99m)Tc-tetrofosmin injection at rest and during stress with 2-day
      protocol. SPECT was started 1h after tracer injection at rest (R) and twice: 1h
      (S1) and 3hs (S3) after injection at stress. LVEF was calculated by the method of
      Germano et al. RESULTS: All LVEF values were significantly lower in CAD patients
      than in the control group. In NMS mean LVEF was at rest similar to those obtained
      1 h and 3 h after stress injection (59.0 +/- 4.1, 60.0 +/- 5.9, 58.0 +/- 4.6,
      respectively; p >0.05). A post-exercise decrease of LVEF was observed in 2 normal
      patients both at S1 and at S3. In CAD group LVEF values were lower at S1 than at
      R (50.8 +/- 13.6 versus 49.3 +/- 12.8; p <0.05) and at S3 were lower than at S1
      (49.3 +/- 12.8 versus 46.0 +/- 12.2;p <0.001). A significant decrease of LVEF was
      found in 18/46 patients 1 h post stress and in 36/46 3 h post stress. In patients
      with reversible perfusion decrease, a significant correlation was found between
      post-exercise deterioration of perfusion and post-exercise LVEF reduction both at
      S1 (r = 0.744; p <0.02) and at S3 (r = 0.734; p <0.02). Stress induced decrease
      in LVEF correlated also with severity of perfusion abnormalities. CONCLUSIONS: In
      the majority of patients with CAD physical stress applied for diagnostic purposes
      results in an impairment of the LV function. A decrease of the LVEF is observed 1
      h after exercise, but it increases in frequency and grows stronger during the
      next 2 h. The post-stress LVEF reduction is related to the severity of perfusion
      abnormalities. Patients with CAD who underwent diagnostic stress test should
      remain under observation during several hours after termination of exercise.

PMID- 15480504
TI  - Long term changes in serum T4, T3, and TSH in benign thyroid disease: proof of a
      narrow individual variation.
AB  - AIM: The diagnosis of abnormalities of thyroid function is generally based on the
      measurement of thyroid hormones and TSH in blood. The recommended reference
      ranges for serum T4 and T3 as well as TSH are quite wide as the result of large
      differences in thyroid function tests in healthy persons. It has been proven that
      the individual variation within an individual is small, compared with the
      variation between individuals. We investigated long term variations of these
      parameters in patients with and without benign thyroid diseases. METHODS: We
      performed long term follow-up serum determinations of T3, T4, and TSH in a total
      of 150 patients for a time period of 3 to 13 years. The majority of patients had
      been put on L-thyroxine. Values of total T3, total T4, free T4 were measured with
      an almost unmodified test (RIA) over the years. RESULTS: The lowest relative
      coefficient of variation (<10%) was observed in the group of patients who had
      been treated with L-thyroxine only. Even for TSH, relatively low cofficients of
      variation were observed in this group. In the group of patients who had not
      received any medication, T3 and T4 showed also a variation of 10%. FT4 and TSH
      revealed a wider range of variation. Even after radioiodine therapy, T3 and T4
      showed only a quite small variation, while TSH demonstrated a wide range with a
      variation of >30%. CONCLUSION: Our data demonstrate that there are only narrow
      variations of serum T4 and T3 within individuals with and without thyroid
      disorders.

PMID- 15480505
TI  - Value of combined XCT/SPECT technology for avoiding false positive planar (123)I
      MIBG scintigraphy.
AB  - AIM: The clinical value of combined XCT/SPECT technology in a single device in
      patients undergoing (123)I-MIBG scintigraphy was analyzed. METHODS: 31 patients
      (19 men, 12 women; mean age 55 years, range: 31-79 years) demonstrating focal
      accumulation in planar (123)I-MIBG scan were further investigated with a double
      headed gamma camera with an X-ray tomograph mounted on the same gantry (GE
      Medical Systems, Millennium VG with Hawkeye, Milwaukee, USA) for anatomical
      definition of the focal (123)I-MIBG uptake. The patients were referred to (123)I
      MIBG scintigraphy because of biochemically (81%) and/or clinically (19%)
      suspected pheochromocytoma. RESULTS: In 23 out of 31 patients (74%) the fused
      images demonstrated physiological accumulation (i. e. intestinal, renal) of
      (123)I-MIBG. In two patients (6%) suspected adrenal MIBG-accumulation was caused
      by inhomogeneous liver uptake. In two patients (6%) focal abdominal accumulation
      was correctly localised in the adrenal glands. Furthermore, the differentiation
      of bone metastasis from a local recurrence for phaeochromocytoma was accurately
      possible for two patients (6%). Adrenal lesions mimicking liver foci were
      correctly localised in the remaining two patients (6%). CONCLUSION: Our study
      demonstrates the clinical value of XCT/SPECT in a single device in patients
      demonstrating focal (123)I-MIBG uptake in planar scintigraphy. The combined
      XCT/SPECT technology provides a higher diagnostic accuracy.

PMID- 15480506
TI  - [Guideline for radioimmunotherapy of rituximab relapsed or refractory CD20(+)
      follicular B-cell non-Hodgkin's lymphoma].
AB  - This guideline is a prerequisite for the quality management in the treatment of
      non-Hodgkin-lymphomas using radioimmunotherapy. It is based on an
      interdisciplinary consensus and contains background information and definitions
      as well as specified indications and detailed contraindications of treatment.
      Essential topics are the requirements for institutions performing the therapy.
      For instance, presence of an expert for medical physics, intense cooperation with
      all colleagues committed to treatment of lymphomas, and a certificate of
      instruction in radiochemical labelling and quality control are required.
      Furthermore, it is specified which patient data have to be available prior to
      performance of therapy and how the treatment has to be carried out technically.
      Here, quality control and documentation of labelling are of greatest importance.
      After treatment, clinical quality control is mandatory (work-up of therapy data
      and follow-up of patients). Essential elements of follow-up are specified in
      detail. The complete treatment inclusive after-care has to be realised in close
      cooperation with those colleagues (haematology-oncology) who propose, in general,
      radioimmunotherapy under consideration of the development of the disease.

PMID- 15480507
TI  - [Procedure guidelines for dynamic renal scintigraphy].
AB  - This procedure guideline describes the procedures for dynamic renal scintigraphy
      with (99m)Tc-MAG3, (123)I-hippuran and (99m)Tc-DTPA. Common clinical applications
      as well as a detailed description of the procedure are given. It also includes
      explanations and hints concerning the analysis, evaluation, interpretation, and
      presentation of the findings.

PMID- 15480508
TI  - Impact of hypoxia and the metabolic microenvironment on radiotherapy of solid
      tumors. Introduction of a multi-institutional research project.
AB  - BACKGROUND: Recent developments in imaging technology and tumor biology have led
      to new techniques to detect hypoxia and related alterations of the metabolic
      microenvironment in tumors. However, whether these new methods can predict
      radiobiological hypoxia and outcome after fractionated radiotherapy still awaits
      experimental evaluation. MATERIAL AND METHODS: The present article will introduce
      a multi-institutional research project addressing the impact of hypoxia and the
      metabolic microenvironment on radiotherapy of solid tumors. The four laboratories
      involved are situated at the universities of Dresden, Mainz, Munich and Wurzburg,
      Germany. RESULTS: The joint scientific project started to collect data obtained
      on a set of ten different human tumor xenografts growing in nude mice by applying
      various imaging techniques to detect tumor hypoxia and related parameters of the
      metabolic microenvironment. These techniques include magnetic resonance imaging
      and spectroscopy, metabolic mapping with quantitative bioluminescence and single
      photon imaging, histological multiparameter analysis of biochemical hypoxia,
      perfusion and vasculature, and immunohistochemistry of factors related to
      angiogenesis, invasion and metastasis. To evaluate the different methods,
      baseline functional radiobiological data including radiobiological hypoxic
      fraction and outcome after fractionated irradiation will be determined.
      CONCLUSION: Besides increasing our understanding of tumor biology, the project
      will focus on new, clinically applicable strategies for microenvironment
      profiling and will help to identify those patients that might benefit from
      targeted interventions to improve tumor oxygenation.

PMID- 15480509
TI  - pO(2) Polarography versus positron emission tomography ([(18)F]
      fluoromisonidazole, [(18)F]-2-fluoro-2'-deoxyglucose). An appraisal of
      radiotherapeutically relevant hypoxia.
AB  - BACKGROUND AND PURPOSE: The aim of the present study was to validate ([(18)F]
      fluoromisonidazole (FMISO) and [(18)F]-2-fluoro-2'-deoxyglucose (FDG) positron
      emission tomography (PET) for determination of radiotherapeutically relevant
      hypoxia by the gold standard for measuring tissue oxygenation in human tumors,
      the computerized polarographic needle electrode system (pO(2) histography).
      PATIENTS AND METHODS: Up to now, a total of 16 patients with a metastatic neck
      lymph node from a primary squamous carcinoma of the head and neck underwent pO(2)
      and PET measurements. Tumor tissue pO(2) was measured with polarographic needle
      electrodes using a pO(2) histograph (Eppendorf). Under CT control, the needle
      electrode was placed in the tumor without general or local anesthesia. To assess
      the biological and clinical relevance of oxygenation measurement, the relative
      frequency of pO(2) readings, with values < or = 2.5, < or = 5.0, and < or = 10.0
      mmHg, as well as mean and median pO(2) were recorded. All PET studies were
      carried out using an ECAT EXACT 922/47 scanner with an axial field of view of
      16.2 cm. FMISO PET consisted of one static scan of the relevant region, performed
      120 min after intravenous administration. The acquisition and reconstruction
      parameters were as follows: 15-min emission scanning and 4-min transmission
      scanning with (68)Ge rod sources. FDG PET of the lymph node metastasis was
      performed 68 +/- 11 min after intravenous administration, applying the whole-body
      tool with 8-min emission scanning and 4-min transmission scanning per bed
      position. RESULTS: In order to detect possible relations between the different
      relevant polarographically measured parameters of tumor hypoxia and FMISO PET
      data-based oxygenation values, the Pearson correlation coefficient was
      calculated. Average (r > 0.5) to high correlation (r > 0.7) was found between
      tumor-to-muscle ratio of FMISO after 2 h and parameters of hypoxic fraction
      (pO(2) readings with values <or = 2.5, < or = 5.0, and < or = 10.0 mmHg as well
      as mean and median). No correlations could be shown between FDG PET parameters
      and polarographically determined tumor oxygenation status. CONCLUSION:
      Summarizing the FMISO uptake represents a global value for macroscopic tumor
      parts. As a noninvasive measurement this method seems highly feasible to evaluate
      the state of oxygenation in subjacent tumors.

PMID- 15480510
TI  - Regional nodal recurrence in the management of breast cancer patients with one to
      three positive axillary lymph nodes. Outcome of patients following tangential
      irradiation without a separate nodal field.
AB  - PURPOSE: To examine the prognosis of breast cancer patients (T1-3, one to three
      positive axillary lymph nodes) and locoregional failure rate after breast
      conserving therapy/modified radical mastectomy and adequate axillary dissection
      following tangential radiotherapy without irradiation of the regional lymph
      nodes. PATIENTS AND METHODS: From 1994 to 2002, the medical records of 183 breast
      cancer patients (T1-3, one to three involved axillary lymph nodes) were examined
      in order to identify those experiencing regional nodal recurrence, with or
      without local recurrence. The median age of the patient population was 58 years
      (range, 28-86 years). All patients underwent surgical treatment, either breast
      conserving therapy (n = 146) or modified radical mastectomy (n = 37). The median
      number of lymph nodes removed was twelve (range, seven to 26 nodes). Irradiation
      was given to the breast through tangential fields. Chemotherapy was administered
      to 101 patients (55%), hormonal therapy to 124 (60%), and combined systemic
      treatment to 47 (26%). RESULTS: The median observation time was 44.4 months
      (range, 11-102 months). Of the 14 patients (7.7%) with a relapse, six (3.3%) had
      a local recurrence, five (2.8%) a regional relapse, and three (1.6%) a
      simultaneous recurrence. Nine out of 14 patients with locoregional relapse
      developed distant failure subsequently and seven of them (78%) died of the
      disease. CONCLUSION: Regional recurrence is uncommon among patients with one to
      three positive axillary lymph nodes treated with surgery, adequate axillary
      dissection, and tangential field irradiation only. The authors conclude that
      regional nodal irradiation should not routinely be given following adequate
      axillary dissection when only one to three lymph nodes are positive.

PMID- 15480511
TI  - Postmastectomy radiotherapy of the chest wall. Comparison of electron-rotation
      technique and common tangential photon fields.
AB  - BACKGROUND AND PURPOSE: Different radiotherapy techniques are being used for
      postmastectomy irradiation. A retrospective analysis of patterns of locoregional
      failure (LRF) after modified radical mastectomy and axillary lymph node
      dissection followed by locoregional radiotherapy with or without systemic
      treatment was performed. Main emphasis was focused on the comparison of two
      postmastectomy radiotherapy techniques. PATIENTS AND METHODS: 287 evaluable
      patients with locally advanced disease and/or adverse pathologic features (pT3
      17% of patients, pT4 35%, multicentricity 25%, pN more than three positive nodes
      and/or pN1biii 70%, "close margins" 29%, infiltration of pectoral fascia 20%)
      with or without adjuvant chemo-hormonal treatment were included between 1989 and
      2000. Median age was 61 years (range 24-88 years). All patients had modified
      radical mastectomy and axillary lymphonodectomy level I-II(III) for primary
      breast cancer. Median total dose of conventionally fractionated radiotherapy to
      the chest wall was 50 Gy (range 46-56 Gy). A local boost to the tumor bed of 10
      Gy was applied in 72 patients. 80% of the patients received supraclavicular and
      60% ipsilateral internal mammary lymph node irradiation of 50 Gy. 19% of the
      patients received adjuvant chemo-hormonal therapy, 38% hormonal therapy, and 27%
      chemotherapy. The median follow-up of patients at risk was 43 months (average 54
      months). RESULTS: The 5-year locoregional tumor control (LRC), LRC first event,
      disease-free, and overall survival were 85%, 91%, 61%, and 70% (Kaplan-Meier
      analysis), respectively. Cox regression analysis showed that stage III (relative
      risk [RR] 1.7), more than three involved axillary lymph nodes (RR 5.1), and
      infiltration of the pectoral fascia (RR 3.2) increased the risk of locoregional
      failure, while positive estrogen receptor status (RR 0.3) was associated with a
      reduced risk. No statistically significant differences in LRC were observed for
      patients treated either with the electron-rotation technique (LRC 92%) or with
      the photon-based technique (LRC 89%; p = 0.9). A subgroup analysis of tumors
      resected with "close margins" showed a higher LRF rate of 25% after electronbeam
      rotation irradiation (n = 180) compared to an LRF of 13% with tangential opposed
      6-MV photon fields (n = 107; p < 0.05). Large primary tumors of > or = 5 cm
      developed LRF in 29% of patients treated with electron-beam-rotation irradiation
      and in 17% of patients with photon-based irradiation (p = 0.1). CONCLUSION: In
      locally advanced breast cancer, the LRC after postmastectomy irradiation with
      both techniques is comparable with published data from randomized studies. The
      tangential opposed photon field technique seems to be beneficial after marginal
      resection (histopathologic "close margins") of the primary tumor.

PMID- 15480512
TI  - Virtual simulation of a boost field in adjuvant radiotherapy of the breast.
AB  - BACKGROUND AND PURPOSE: In CT-based adjuvant radiotherapy of the breast, virtual
      simulation techniques have been developed. This paper demonstrates a simple
      virtual simulation of a boost field. MATERIAL AND METHODS: 41 fields were planned
      virtually, 26 as electron beams, 15 as tangential photon beams. RESULTS:
      Depending on the user's expertise the geometric accuracy was high; possible
      sources of error are illustrated. Resulting field sizes tended to be slightly
      larger compared to conventional simulation when applying the same rules of field
      definition. Differences in focus-skin distances with consecutive divergence
      effects as well as partial volume effects were discussed to be causal.
      CONCLUSION: Virtual simulation of a boost field has the potential to elegantly
      link the simplicity of a conventional simulation with the accurate tumor bed
      identification provided by a CT data set. It was shown to be feasible and
      favorable with regard to the patient, the medical staff, and the simulator time.
      Moreover, it offers a visualization of dose distributions, which was found
      helpful in some cases.

PMID- 15480513
TI  - Accelerated partial breast irradiation with iridium-192 multicatheter PDR/HDR
      brachytherapy. Preliminary results of the German-Austrian multicenter trial.
AB  - PURPOSE: To evaluate perioperative morbidity, toxicity, and cosmetic outcome in
      patients treated with interstitial brachytherapy to the tumor bed as the sole
      irradiation modality after breast-conserving surgery. PATIENTS AND METHODS: From
      November 1, 2000 to January 31, 2004, 176 women with early-stage breast cancer
      became partakers in a protocol of tumor bed irradiation alone using pulsed-dose
      rate (PDR) or high-dose-rate (HDR) interstitial multicatheter implants. Patients
      became eligible, if their tumor was an infiltrating carcinoma < or = 3 cm in
      diameter, the surgical margins were clear by at least 2 mm, the axilla was
      surgically staged node-negative, the tumor was estrogen and/or progesterone
      receptor-positive, well or moderately differentiated (G1/2), the tumor did not
      contain an extensive intraductal component (EIC) and the patient's age was > 35
      years. Implants were positioned using a template guide, delivering either 49.8 Gy
      in 83 consecutive hours (PDR) or 32.0 Gy in two daily fractions over 4 days
      (HDR). Perioperative morbidity, toxicity, and cosmetic outcome were assessed.
      Interim findings of the first 69 patients, who were treated in this multicenter
      trial, after a median follow-up of 24 months (range, 15-39 months) are presented.
      RESULTS: One of the 69 patients (1.4%) developed a bacterial infection of the
      implant. No other perioperative complications, for example bleeding or hematoma,
      were observed. Acute toxicity was low: 2.9% of the patients (2/69) experienced
      mild radiodermatitis. Late toxicity: hypersensation/mild pain 7.2% (5/69),
      intermittent but tolerable pain 1.4% (1/69), mild dyspigmentation 10.1% (7/69),
      mild fibrosis 11.6% (8/69), moderate fibrosis 1.4% (1/69), mild telangiectasia (<
      1 cm(2)) 11.6% (8/69), and moderate teleangiectasia (1-4 cm(2)) 1.4% (1/69). Good
      to excellent cosmetic results were observed in 92.4% of the patients evaluated.
      All patients (n = 176) remained disease-free to the date of evaluation.
      CONCLUSION: This analysis indicates that accelerated partial breast irradiation
      with iridium-192 interstitial multicatheter PDR/HDR implants is feasible with low
      perioperative morbidity, low acute and mild late toxicity, and does not
      significantly affect cosmetic results at a median follow-up of 24 months.

PMID- 15480514
TI  - Radiation-induced plexopathy and fibrosis. Is magnetic resonance imaging the
      adequate diagnostic tool?
AB  - PURPOSE: To investigate magnetic resonance imaging (MRI) features of radiation
      induced plexopathy (RIP) and radiation-induced fibrosis frequently associated
      with RIP. PATIENTS AND METHODS: Seven patients with late radiation sequelae in
      the supraclavicular region were examined with MRI after a median interval of 7
      years (range, 5-18 years) following radiotherapy and 4-7 years after the onset of
      RIP. Four patients had RIP plus severe soft-tissue fibrosis, two RIP without soft
      tissue fibrosis (n = 2/6), and one patient fibrosis without RIP. Patients
      underwent surgery of breast cancer (n = 6) or chest wall relapse (n = 1) and
      radiotherapy to the supraclavicular fossa with cobalt with an anterior portal in
      fractions of 1.7-2.6 Gy to 43-51.6 Gy in 3 cm depth. All patients were relapse
      free at the time of MRI. Fibrosis and RIP were scored clinically (RTOG
      classification). Fibrosis of the supraclavicular and/or axillary region was
      marked in three and mild in two patients. RIP was mild, marked and severe in two
      patients each. MRI was performed with a 1.5-T unit including coronal STIR,
      coronal and transversal T2-weighted, transversal T1-weighted and fat-saturated
      post-contrast (gadolinium-DTPA) spin echo sequences. RESULTS: The brachial plexus
      appeared normal in all patients, but subtle changes of adjoining tissue (slight,
      linear signal intensity in T2-weighted images or contrast enhancement surrounding
      the plexus) were detected in patients with RIP (n = 4/6) and the patient without
      RIP (n = 1). However, alterations of the soft tissue (marked signal intensity in
      T2-weighted sequences) correlated well with the clinical degree of fibrosis and
      were restricted to areas of marked to severe fibrosis (n = 3/3). CONCLUSION:
      Reliable MRI signs of RIP could not be identified. The severity of fibrosis
      closely corresponded to MRI features. The role of MRI in the diagnostic work-up
      of RIP is, therefore, the exclusion of tumor relapse.

PMID- 15480515
TI  - Analysis of the action of the restriction endonuclease AluI using three different
      comet assay protocols.
AB  - BACKGROUND AND PURPOSE: The comet assay offers the opportunity to measure the
      amount of DNA damage and the effectiveness of DNA repair in single cells. In a
      first part, experiments are presented comparing three different protocols of the
      comet assay technique with respect to the analysis of the induction of DNA damage
      after X-irradiation in isolated human lymphocytes and CHO cells. In a second
      part, the restriction enzyme AluI, an agent producing DNA double-strand breaks
      exclusively, was introduced into CHO cells by electroporation and the effects
      were analyzed using the different comet assay protocols. The experiments were
      carried out in order to test the assertion that comet assay techniques can
      measure different types of DNA damages at different pH conditions of lysis and
      electrophoresis. MATERIAL AND METHODS: Three different comet assay protocols were
      used for the analysis of DNA damage in lymphocytes and CHO cells. RESULTS: The
      results clearly indicate that among the three protocols the modified comet assay
      technique used by the authors showed the highest sensitivity in the radiotherapy
      relevant dose range between 0 and 2 Gy. All three protocols were capable of
      detecting an effect by AluI. This effect, however, was clearly different from
      radiation effects. Whereas after radiation exposure all cell nuclei show a dose
      dependent increase in DNA content in the comet tail, most of the cell nuclei were
      unaffected by an AluI uptake. Nevertheless, there was an effect by AluI that
      could be detected in all three assay versions: between 5% and 15% of the nuclei
      showed clearly abnormal comet morphologies. CONCLUSION: Neither the strictly
      alkaline nor the strictly neutral comet assay is applicable in the radiation dose
      range of about 2 Gy. The restriction enzyme results show that other factors than
      just DNA strand breaks contribute to DNA migration into the tail of the comets.

PMID- 15480516
TI  - [Intestinal malperfusion in critical care patients].
AB  - Due to the bowel's poor tolerance of hypoxia, intestinal malperfusion presents as
      a grave disease with high mortality. The intensivist is confronted with this
      condition in association with other underlying diseases, in the course of
      surgery, during application of medication or associated with invasive therapy. In
      a critical care setting, the non-occlusive mesenteric ischemia (NOMI) is of
      increasing importance. Since critical care patients often lack clinical symptoms,
      special attention is required and one main factor of the patient's prognosis is
      early diagnosis. This review summarizes pathophysiology and diagnostic aspects
      and the range of therapeutic and preventive measures.

PMID- 15480520
TI  - [Autologous cultured skin substitutes].
AB  - Progress in cell culture and biomaterial technologies has resulted in
      commercially available autologous and allogeneic skin substitutes that are
      composed of keratinocytes and/or fibroblats, in part combined with allogeneic
      (fibrin) or xenogeneic (collagen, hyaluronan) matrix substances. So far, clinical
      testing of tissue-engineered products focused on chronic wounds (vascular leg
      ulcers, diabetic foot ulcers); another major indication, however, is large acute
      skin defects (burns). During the last decade, partly-controlled clinical trials
      have been performed with several cultured skin substitutes, studying primarily
      vascular leg ulcers; a few of these products have been approved for defined
      indications by the regulatory authorities of various countries. To fulfill
      regulatory requirements and be eligible for reimbursement, safety as well as cost
      effectiveness have to be documented for these novel therapies in contrast to
      established methods for clearly defined clinical settings; this, in combination
      with restricted health care resources, is actually hampering the clinical
      breakthrough of tissue engineering in the treatment of skin wounds, despite
      undiminished research activities.

PMID- 15480518
TI  - [Management of coagulation after multiple trauma].
AB  - Hemorrhage after traumatic injury results in coagulopathy which only worsens the
      situation. This coagulopathy is caused by depletion and dilution of clotting
      factors and platelets, increased fibrinolytic activity, hypothermia, metabolic
      changes and anemia. The effect of synthetic colloids used for compensating the
      blood loss, further aggravates the situation through their specific action on the
      hemostatic system. Bedside coagulation monitoring permits relevant impairment of
      the coagulation system to be detected very early and the efficacy of the
      hemostatic therapy to be controlled directly. Administration of fresh frozen
      plasma (FFP), platelet concentrates and antifibrinolytic agents is essential for
      restoring the impaired coagulation system in trauma patients. Clotting factor
      concentrates should be administered if coagulopathy is based on diagnosed
      depletion of clotting factors, if FFP is not available and if transfusion of FFP
      is insufficient to treat the coagulopathy. Recombined FVIIa is frequently
      employed during severe bleeding which could not be treated by conventional
      methods but the results of on-going clinical trials are not yet available.

PMID- 15480521
TI  - [Lung transplantation. Possibilities and limitations].
AB  - Lung transplantation is an option for patients with endstage pulmonary diseases
      without contraindications. Recent European studies showed a survival benefit for
      patients with cystic fibrosis, fibrosis and emphysema after lung transplantation.
      Early mortality has been reduced recently by surgical improvements. Life
      expectancy after lung transplantation has improved in recent years but is still
      lower than in patients with other solid organ transplantations. Quality of life
      is consistently improved but exercise tolerance keeps reduced in comparison to
      the normal population. Specific problems described in detail are frequent organ
      rejections and infections, airway problems and a high incidence of malignant
      diseases. 5-year survival after lung transplantation is in average 60%.

PMID- 15480522
TI  - [Antireflux therapy--more than acid reduction?].
AB  - Because gastroesophageal reflux disease (GERD) is a motility disorder, acid
      reduction with proton pump inhibitors (PPI) remains a symptomatic therapy with a
      recurrence rate of over 90% after discontinuation of acid suppression. This
      "therapeutic dilemma" becomes obvious in patients not responding sufficiently to
      the conventional medication (therapy resistance, necessity of high PPI doses,
      volume reflux). In this manuscript we analyze additional factors that may play a
      role in the pathogenesis and interpretation of GERD. These additional factors
      include gastroesophageal motility and esophageal barrier functions as well as
      duodenogastroesophageal reflux and Helicobacter pylori infection. In addition,
      basic problems in interpretation of therapeutic success such as placebo effect,
      spontaneous remission of GERD, the role of sensory function and subjective
      interpretation of symptoms and the overlap between physiological and pathological
      reflux as well as functional disorders will be discussed.

PMID- 15480523
TI  - [Multiple focal liver lesions of a 33 year-old female. Presentation of an
      unexpected differential diagnosis].
AB  - We report the case of a 33 year-old female with a history of 16 years of oral
      contraception who had been admitted to hospital for further diagnosis of multiple
      focal liver lesions; laboratory findings showed elevated levels of gamma-GT und
      AP. Diagnostic procedures showed no primary malignancy as possible reason for
      metastasis. All further imaging procedures compared with doppler-enhanced
      ultrasound did not help in diagnosis and lead to inconsistent results.
      Transcutaneous liver-biopsy showed normal liver histology. In laparoscopic biopsy
      the result was multifocal adenoma. Because of the rupture risk and potential
      malignant transformation and no change of sonomorphologic appearance within 12
      months a liver-segment resection has been undertaken. Pathology revealed the
      diagnosis of a multifocal hyperplastic-adenomateous focal-nodular hyperplasia.
      This case shows that there is no need to use different methods of medical imaging
      redundantly. We favor a fine-needle double-puncture (lesion and extra-lesion) and
      tissue examination through an experienced pathologist. A total resection of the
      lesion is necessary in case of resting uncertainty to characterize its tissue
      characteristics.

PMID- 15480524
TI  - Feeding and reproductive behaviour in fallow bucks (Dama dama).
AB  - Observations on individually marked fallow deer (Dama dama) in central Italy were
      performed over 2 years in order to analyse time budgets of four age and sex
      classes. The aim was to test whether feeding activity was influenced by mating
      activity, forage quality or physiological constraints during the rut. Only adult
      males (bucks) completely ceased feeding during the rutting season, well before
      the actual start of mating behaviour and concurrently with the phenomenon of
      scent-urination, and spending most of their daily time completely inactive. All
      other age and sex classes were unaffected in their feeding behaviour by the
      rutting season. Indeed, females and young males showed a marked increase in
      grazing in response to an improvement in forage quality from summer to autumn.
      These results seem to confirm the hypothesis that hypophagia, displayed only by
      bucks, may be of no adaptive value in itself. On the other hand, it may be a by
      product of other physiological processes occurring during the rut, inducing scent
      urination, which plays an important role in intraspecific recognition and sexual
      attraction.

PMID- 15480525
TI  - [Therapy of MS symptoms. Here also are guidelines necessary].

PMID- 15480526
TI  - [Symptomatic therapy of multiple sclerosis].

PMID- 15480527
TI  - [Causes, diagnosis and treatment of suicidality].
AB  - In Germany, each year more than 11,000 people commit suicide. Rates of attempted
      suicide are estimated to be tenfold higher. Psychosocial as well as biological
      causes play an important role in the etiology of suicidality. Patients suffering
      from affective disorders, alcohol and drug abuse, and psychotic disorders are
      considered to be the most important high-risk groups. Careful diagnosis of
      suicidality is a precondition for successful therapy. Acute treatment is based on
      psychopharmacological as well as on psychotherapeutic strategies. In the case of
      acute danger, short-term goals consist in gaining time and actively providing
      direct support. In the long run, treatment of the underlying psychiatric disorder
      and stabilisation of the daily life situation become more important. There is no
      scientific evidence for the hypothesis that selective serotonin reuptake
      inhibitors (SSRIs) increase the risk of suicide.

PMID- 15480528
TI  - [Diagnosis and therapy of post-traumatic stress disorders in childhood and
      adolescence. Responsibilities of the child and adolescent psychiatric trauma
      outpatient clinic].
AB  - This article presents an overview of the etiology, clinical characteristics,
      assessment, and treatment of PTSD in children and adolescents. Diagnostic
      criteria of DSM-IV and ICD-10 for PTSD in adults may not adequately describe this
      disorder especially in toddlers and preschool children, because specific PTSD
      symptoms may vary according to the developmental stage of the child. Prevalence
      of PTSD in adolescence is similar to that in adulthood. Children who exhibit high
      degrees of psychopathology before traumatic exposure, who are exposed to high
      levels of trauma for an extended period, or who directly experienced the event
      face a high risk to develop PTSD and other later adverse outcomes. Parental
      support and other social factors also emerge as strong predictors of differential
      risk among traumatized children. Cognitive-behavioral therapy is a well-assessed
      intervention strategy recommended for children and adolescents with PTSD while
      there are no controlled trials of pharmacological treatments. The outpatient
      clinic for traumatized children and adolescents of the University Clinic of
      Aachen is introduced and clinical characteristics of children seeking help are
      described. In addition, the social network and cooperating services are
      illustrated.

PMID- 15480529
TI  - [Emotional dysfunction, psychopathy and cognitive neuroscience. What is new and
      what are the consequences].
AB  - This article provides a review of recent findings in the cognitive neurosciences
      on antisocial personality disorders. There is accumulating evidence that the
      subtype of psychopathy is characterized by emotional dysfunction not only on the
      behavioral level but also by structural and functional abnormalities of the
      brain. Although the findings are not yet conclusive, they are already being
      discussed controversially with respect to the question of accountability of
      persons with psychopathy. False conclusions dominating these considerations are
      discussed and corrected. The findings open a new discussion of the relevance of
      emotional function and dysfunction for accountability.

PMID- 15480530
TI  - [Ecology of the brain. A systemic view for psychiatry and psychotherapy].
AB  - Present neurobiological concepts of the mind-brain relationship often tend
      towards a reductionist view of subjectivity. In contrast to this, an ecological
      or systemic view of the brain is outlined which regards cognition and
      consciousness as components in a circular causality of organism and environment.
      In these cyclic processes, the brain functions as an organ of transformation
      which mutually translates elementary and complex system states into each other,
      thus allowing the organism to develop integral options of perception and action
      in its environment. Since these interactions, on their part, continuously change
      the microstructure of the brain, it has to be regarded as an organ that is formed
      biologically, socially as well as historically. The consequences of this
      ecological conception for our view of mental illness, for therapeutic approaches
      and for the role of subjectivity in psychiatry are pointed out.

PMID- 15480531
TI  - [Psychiatry in transitions of the public health system].

PMID- 15480533
TI  - Allelic variation at the VRN-1 promoter region in polyploid wheat.
AB  - Vernalization, the requirement of a long exposure to low temperatures to induce
      flowering, is an essential adaptation of plants to cold winters. We have shown
      recently that the vernalization gene VRN-1 from diploid wheat Triticum monococcum
      is the meristem identity gene APETALA1, and that deletions in its promoter were
      associated with spring growth habit. In this study, we characterized the allelic
      variation at the VRN-1 promoter region in polyploid wheat. The Vrn-A1a allele has
      a duplication including the promoter region. Each copy has similar foldback
      elements inserted at the same location and is flanked by identical host direct
      duplications (HDD). This allele was found in more than half of the hexaploid
      varieties but not among the tetraploid lines analyzed here. The Vrn-A1b allele
      has two mutations in the HDD region and a 20-bp deletion in the 5' UTR compared
      with the winter allele. The Vrn-A1b allele was found in both tetraploid and
      hexaploid accessions but at a relatively low frequency. Among the tetraploid
      wheat accessions, we found two additional alleles with 32 bp and 54 bp deletions
      that included the HDD region. We found no size polymorphisms in the promoter
      region among the winter wheat varieties. The dominant Vrn-A1 allele from two
      spring varieties from Afghanistan and Egypt ( Vrn-A1c allele) and all the
      dominant Vrn-B1 and Vrn-D1 alleles included in this study showed no differences
      from their respective recessive alleles in promoter sequences. Based on these
      results, we concluded that the VRN-1 genes should have additional regulatory
      sites outside the promoter region studied here.

PMID- 15480534
TI  - QTL mapping of Sclerotinia midstalk-rot resistance in sunflower.
AB  - In many sunflower-growing regions of the world, Sclerotinia sclerotiorum (Lib.)
      de Bary is the major disease of sunflower (Helianthus annuus L.). In this study,
      we mapped and characterized quantitative trait loci (QTL) involved in resistance
      to S. sclerotiorum midstalk rot and two morphological traits. A total of 351 F3
      families developed from a cross between a resistant inbred line from the
      germplasm pool NDBLOS and the susceptible line CM625 were assayed for their
      parental F2 genotype at 117 codominant simple sequence repeat markers. Disease
      resistance of the F3 families was screened under artificial infection in field
      experiments across two sowing times in 1999. For the three resistance traits
      (leaf lesion, stem lesion, and speed of fungal growth) and the two morphological
      traits, genotypic variances were highly significant. Heritabilities were moderate
      to high (h2=0.55-0.89). Genotypic correlations between resistance traits were
      highly significant (P<0.01) but moderate. QTL were detected for all three
      resistance traits, but estimated effects at most QTL were small. Simultaneously,
      they explained between 24.4% and 33.7% of the genotypic variance for resistance
      against S. sclerotiorum. Five of the 15 genomic regions carrying a QTL for either
      of the three resistance traits also carried a QTL for one of the two
      morphological traits. The prospects of marker-assisted selection (MAS) for
      resistance to S. sclerotiorum are limited due to the complex genetic architecture
      of the trait. MAS can be superior to classical phenotypic selection only with low
      marker costs and fast selection cycles.

PMID- 15480535
TI  - Nucleotide polymorphism in the Adh1 locus region of the wild rice Oryza
      rufipogon.
AB  - Nucleotide variation in the alcohol dehydrogenase (Adh1) locus region of the wild
      rice Oryza rufipogon and its related species was analysed to clarify the
      maintenance mechanism of DNA variation in Oryza species. The estimated nucleotide
      diversity in the Adh1 locus region of O. rufipogon was 0.002, which was one of
      the lowest values detected in nuclear loci of plant species investigated so far.
      Tests of neutrality detected significantly negative deviation from the neutral
      mutation model for the coding region, especially for replacement sites. When each
      of the ADH1 domains was considered, significance was detected only for the
      catalytic domain 1. These results suggest purifying selection in the Adh1 coding
      region. In the phylogenetic tree of Oryza species based on Adh1 variation,
      cultivated rice O. sativa subspp. japonica and indica were included in the
      cluster of O. rufipogon. The genetic distance of the Adh1 region between O.
      rufipogon and O. sativa was as low as the nucleotide diversity of O. rufipogon.
      These results imply that O. rufipogon and O. sativa cannot be classified based on
      the nucleotide variation of Adh1. No replacement divergence between O. rufipogon
      and the other three A-genome species (O. glumaepatula, O. barthii and O.
      meridionalis) were detected, indicating that ADH1 is conserved in the A-genome
      species. On the other hand, between O. rufipogon and the E-genome species O.
      australiensis, replacement changes were detected only in the catalytic domain 1.
      The difference in replacement substitutions between the A- and E-genome species
      may be related to adaptive changes in the ADH1 domains, reflecting environmental
      differences where the species encounter anaerobic stress.

PMID- 15480536
TI  - In vivo proliferation of differentiated pancreatic islet beta cells in transgenic
      mice expressing mutated cyclin-dependent kinase 4.
AB  - AIMS/HYPOTHESIS: It has previously been hypothesised that highly differentiated
      endocrine cells do not proliferate or regenerate. However, recent studies have
      revealed that cyclin-dependent kinase 4 (CDK4) is necessary for the proliferation
      of pancreatic islet beta cells. The aim of this study was to determine whether
      activation of CDK4 can potentially be used as a radical treatment for diabetes
      without malignant transformation. METHODS: We generated transgenic mice
      expressing mutant CDK4 under the control of the insulin promoter to examine the
      effect of activated CDK4 overexpression in the postnatal development of
      pancreatic islets. RESULTS: In the transgenic mice, total CDK4 protein expression
      was increased by up to 5-fold, with a concomitant increase in CDK4 activity
      indicated by the detection of phosphorylated Rb protein in pancreatic islets.
      Histopathologically, many cells tested positive for proliferating cell nuclear
      antigen, and pancreatic islets displayed hyperplasia due to the extreme
      proliferation of beta cells containing a large number of insulin granules.
      Pancreatic islet alpha, delta and PP cells did not increase. Over an 18-month
      observation period, the transgenic mice did not develop insulinoma. Levels of
      expression of GLUT1 and c-myc were comparable to those in the littermates of the
      transgenic mice. GLUT2 expression was identified in the pancreatic islets of
      transgenic mice. No significant differences in telomerase activities were
      detected between transgenic mice and their littermates. Transgenic mice were
      superior to their littermates in terms of glucose tolerance and insulin secretion
      in response to the intraperitoneal injection of glucose, and hypoglycaemia was
      not observed. CONCLUSIONS/INTERPRETATION: Activated CDK4 stimulates postnatal
      pancreatic beta cell proliferation, during which the highly differentiated
      phenotypes of pancreatic islet beta cells are preserved without malignant
      transformation.

PMID- 15480537
TI  - Ischaemic preconditioning does not protect the heart in obese and lean animal
      models of type 2 diabetes.
AB  - AIMS/HYPOTHESIS: The prevalence of type 2 diabetes mellitus is increasing
      worldwide with obese diabetic patients constituting the majority of this
      population. Type 2 diabetes is associated with increased morbidity and mortality
      after acute myocardial infarction. Previous experimental studies of ischaemia
      reperfusion tolerance in diabetes have only been performed in animal models of
      type 1 diabetes mellitus, yielding conflicting data. The aim of the present study
      was to characterise and compare the tolerance to ischaemia and effects of
      ischaemic preconditioning (IPC) in hearts from obese Zucker diabetic fatty (ZDF)
      and lean Goto-Kakizaki (GK) type 2 diabetic rats, using non-obese Zucker and
      Wistar rats as respective controls. METHODS: The two rat strains were divided
      into 8 groups. The ZDF study (n=47) consisted of: Control -IPC, Control +IPC, ZDF
      -IPC and ZDF +IPC. The GK study (n=38) consisted of: Control -IPC, Control +IPC,
      GK -IPC and GK +IPC. Hearts, which were studied in a Langendorff preparation
      perfused with Krebs-Henseleit buffer, were subjected or not to IPC (+IPC, -IPC)
      before 50 minutes of regional ischaemia and 120 minutes reperfusion. RESULTS:
      Ischaemic reperfusion injury was smaller in obese (p<0.05) and lean (p<0.05) type
      2 diabetic animals than in their respective control animals. IPC reduced
      ischaemic reperfusion injury during reperfusion in non-diabetic control rats
      (p<0.01), but failed to protect hearts from both diabetic animal models. Post
      ischaemic haemodynamic recovery was impaired in the ZDF rats compared to both
      control and GK rats (p<0.05). CONCLUSIONS/INTERPRETATION: Ischaemic
      preconditioning does not protect hearts from obese or lean type 2 diabetic
      animals. However, the susceptibility of the type 2 diabetic myocardium to
      ischaemic damage is lower than in non-diabetic hearts. The method described here
      could be used as a tool to study the pathogenesis of increased cardiovascular
      morbidity and mortality in type 2 diabetes.

PMID- 15480538
TI  - Long-term effects of advice to consume a high-protein, low-fat diet, rather than
      a conventional weight-loss diet, in obese adults with type 2 diabetes: one-year
      follow-up of a randomised trial.
AB  - AIMS/HYPOTHESIS: This study compared the long-term weight loss and health
      outcomes at 1-year follow-up, after a 12-week intensive intervention consisting
      of two low-fat, weight-loss diets, which differed in protein content. METHODS: We
      randomly assigned 66 obese patients (BMI: 27-40 kg/m2) with type 2 diabetes to
      either a low-protein (15% protein, 55% carbohydrate) or high-protein diet (30%
      protein, 40% carbohydrate) for 8 weeks of energy restriction (approximately 6.7
      MJ/day) and 4 weeks of energy balance. Subjects were asked to maintain the same
      dietary pattern for a further 12 months of follow-up. RESULTS: The study was
      completed by 38 of the subjects, with equal dropouts in each group. At Week 64,
      weight reductions against baseline were -2.2+/-1.1 kg (low protein) and -3.7+/
      1.0 kg (high protein), p<0.01, with no diet effect. Fat mass was not different
      from baseline in either group. At Week 12, both diets reduced systolic and
      diastolic blood pressure by 6 and 3 mm Hg respectively, but blood pressure
      increased more with weight regain during follow-up in the low-protein group (p<
      or =0.04). At Week 64, both diets significantly increased HDL cholesterol and
      lowered C-reactive protein concentrations. There was no difference in the urinary
      urea : creatinine ratio at baseline between the two groups, but this ratio
      increased at Week 12 (in the high-protein group only, p<0.001, diet effect),
      remaining stable during follow-up in both diets. CONCLUSIONS/INTERPRETATION: A
      high-protein weight-reduction diet may in the long term have a more favourable
      cardiovascular risk profile than a low-protein diet with similar weight reduction
      in people with type 2 diabetes.

PMID- 15480539
TI  - Insulin resistance is a risk factor for progression to type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Glucose homeostasis is determined by an interplay between
      insulin secretion and insulin action. In type 1 diabetes, autoimmune destruction
      of pancreatic beta cells leads to impaired insulin secretion. However, the
      contribution of impaired insulin action (insulin resistance) to the development
      of type 1 diabetes has received little attention. We investigated whether insulin
      resistance was a risk factor for progression to type 1 diabetes. METHODS: Islet
      antibody-positive first-degree relatives of type 1 diabetes probands were
      followed for 4.0 years (median). Insulin secretion was measured as first-phase
      insulin response (FPIR) to intravenous glucose. Insulin resistance was estimated
      by homeostasis model assessment of insulin resistance (HOMA-R). We compared
      subjects who progressed (n=43) and subjects who did not progress (n=61) to
      diabetes, including 21 pairs matched for age, sex, islet antibodies and FPIR.
      RESULTS: Progressors had higher insulin resistance relative to insulin secretion
      at baseline (median HOMA-R : FPIR 0.033 vs 0.013, p<0.0001). According to Cox
      proportional hazards analysis, islet antibody number, FPIR, fasting plasma
      glucose, fasting serum insulin, HOMA-R and log(HOMA-R : FPIR) were each
      predictive of progression to diabetes. However, log(HOMA-R : FPIR) (hazard ratio
      2.57 per doubling, p<0.001) was the only metabolic variable independently
      associated with progression. In the matched comparison, progressors had higher
      fasting glucose, fasting insulin, HOMA-R and HOMA-R : FPIR, both at baseline and
      during the follow-up pre-clinical phase. CONCLUSIONS/INTERPRETATION: Relatives
      positive for islet antibodies who progress most rapidly to diabetes have a subtle
      disturbance of insulin-glucose homeostasis years before the onset of symptoms,
      distinguished by greater insulin resistance for their level of insulin secretion.
      Taking steps to reduce this insulin resistance could therefore delay the
      development of type 1 diabetes.

PMID- 15480540
TI  - [Acute joint infection--diagnosis and treatment].
AB  - The acute joint infection is a rare condition; the delayed diagnosis may lead to
      significant joint destruction. Diagnostic tools are the c-reactive protein and
      joint aspiration. Today arthroscopic treatment options are suitable tools for the
      treatment of such conditions. Arthroscopic lavage and debridement with additional
      systemic antibiotic treatment proofed to be very effective in an infected joint.
      If there are continuous signs of infection even with antibiotic treatment,
      rearthroscopy within few days is indicated. The number of rearthroscopies is
      related to the initial stage of the infection. With a shaver thorough debridement
      of all necrotic tissue as well as resection of adhesions is performed without
      complete resection of the intact and noninfected synovial membrane. The use of
      intraarticular resorbable antibiotic fleece is possible, but not generally
      recommended. Suction irrigation systems are only rarely indicated. If there is
      bony involvement, open arthrotomy still is the golden standard.

PMID- 15480542
TI  - [Procedures for treatment of joint mechanics impairment in the rotating Endo
      model knee prosthesis].
AB  - In cases of mechanical damage of the Endo model rotating knee prosthesis, it is
      not necessary to change the complete prosthesis. Isolated replacement of the
      mechanics is possible. We changed a sled prosthesis of a 66-year-old patient to a
      rotating knee prosthesis because of ligament instability. After the patient fell
      and traumatized the operated knee, she experienced pain during weight bearing and
      instability. Because clinical and fluoroscopic examinations verified instability
      of the prosthesis, we decided to change the mechanics of the rotating knee
      prosthesis. In conclusion, mechanical damage of a rotating knee prosthesis is a
      rare complication. Operative treatment is easy to manage if replacement parts and
      instruments to change the mechanics have been organized preoperatively.

PMID- 15480541
TI  - [AMC unicondylar prosthesis].
AB  - Since its introduction in the 1970s, unicompartmental knee arthroplasty (UKA) has
      become a standardized routine technique. Increasing experience in determining the
      indication for UKA and improvements in design and materials of the prosthesis
      have led to better results. The AMC UKA has an unconstrained mobile bearing with
      congruent area contact from 0 degrees to 30 degrees of flexion. The principle is
      that a polyethylene mobile bearing, concavely spherical above and flat below, can
      maintain perfect congruity between the spherical metal femoral condyle and the
      flat metal tibial plateau. This ensures complete freedom to rotate and slide upon
      one other with physiologic kinematic and low intrinsic stability. The low contact
      stress results in reduced polyethylene wear. The 361 AMC UKA replacements of the
      current study showed safe anchorage of the prosthesis and good durability of the
      mobile bearings. The clinical results of the investigated patients demonstrate
      that the AMC UKA is a successful concept. The comparison of 30 minimally invasive
      UKA with 30 conventional UKA and 30 total knee replacements shows an advantage of
      the minimally invasive technique with regard to reduced rehabilitation time. The
      accuracy of implantation was comparable between the conventional and the
      minimally invasive techniques.

PMID- 15480543
TI  - [Multistep surgery for spondylosyndesis. Treatment concept of destructive
      spondylodiscitis in patients with reduced general condition].
AB  - OBJECTIVE: Retrospective assessment of multistage surgery in the treatment of
      progressive spondylodiscitis in patients with critical physical status. PATIENTS:
      A total of 34 patients (mean age 58.6 years) with 37 progressive spondylodiscitis
      foci and destruction of one to three vertebral segments (1.9 mean) were recorded
      within an 8-year period. Time between first complaints and operative treatment
      was 3 months (mean). Preoperative health status was critically reduced in 11
      patients (ASA IV) and poor general condition (ASA III) was seen in 23 patients
      when vital indication was seen preoperatively. Considerable systemic disease
      (n=31), further infection focus (n=18), and nosocomial trauma (n=5) were causally
      related. Spondylodiscitis was seen more frequently in the lumbar (n=20) and
      thoracolumbar than in the thoracic (n=10) and cervical spine (n=1).
      Staphylococcus aureus was detectable from operative specimens and hemoculture in
      15 cases, MRSA in 6 of these. METHODS: In cases of monosegmentary involvement
      (n=7) ventral debridement, biopsy, and application of antibiotic chains were
      followed by autologous interbody bone grafting in a second stage operation. In 29
      cases with destruction of two (n=27) and three (n=3) segments, posterior
      instrumentation including laminectomy in 4 patients was completed by anterior
      debridement and application of antibiotic chains during a first surgical
      intervention. After stabilization of physical condition and having reached a
      macroscopically indisputable implant bed, the ventral fusion with autologous
      interbody bone grafting or cage in combination with a plate or internal fixation
      system was performed as the last of several surgical steps. RESULTS: No case of
      perioperative mortality was observed. Intensive care continued 9.1 days and
      hospitalization 49.5 days (mean). During a 37.6-month follow-up two late
      recurrences were observed. CONCLUSION: A multistep surgical procedure under
      protection of dorsal instrumentation can limit perioperative mortality in
      patients in critical general condition by avoiding an extended one stage
      dorsoventral spondylodesis. After eradication of further infection foci and
      stabilization of physical condition, ventral instrumentation is completed under
      elective conditions.

PMID- 15480544
TI  - [Post-traumatic shoulder instability in adolescence].
AB  - BACKGROUND: Post-traumatic shoulder instability in adolescence represents a very
      rare condition. However, most of these patients develop recurrent shoulder
      dislocations over time. METHODS: We report about a retrospective study, which
      included 32 patients younger than 16 years of age. The mean follow-up was 5
      years. Our evaluation focussed on patients' age at the time of first shoulder
      dislocation, type of injury, and the results after conservative and operative
      treatment. RESULTS: After the first dislocation, all shoulders were immobilized
      for 3 weeks and were treated with physiotherapy afterwards. Of these 32 patients,
      30 (94%) developed recurrent shoulder dislocations. Eight patients remained in a
      conservative regimen (age <15 years) and 21 patients were operated for persistent
      shoulder instability (age >15 years). The recurrence rate was 8 of 21 patients
      (36.5%) in the operative group and 4 of 8 patients in the conservative group. At
      the time of follow-up, 4 of 8 conservatively treated patients had returned to
      their former sports activities and 15 of 21 (71%) in the operated group.
      CONCLUSIONS: Our results on post-traumatic shoulder instability in adolescence
      show high recurrence rates in both conservative and operative groups. After
      adolescence, including ossification of the glenoid, operative treatment is able
      to decrease the recurrence rate and to increase the sports ability of these young
      patients.

PMID- 15480545
TI  - [Medial unicompartmental knee replacement using the "Oxford Uni" meniscal bearing
      knee].
AB  - Medial unicompartmental knee replacement (UKR) has many advantages over total
      replacement (TKR) including better function and reduced morbidity. However, the
      long-term failure rates of fixed-bearing UKR are high, especially because of
      polyethylene wear. The fully congruent mobile bearing of the Oxford UKR exhibits
      minimal polyethylene wear, failure from this cause does not seem to occur before
      10 years. The instrumentation allows precise implantation to restore isometric
      function of the ligaments. During its 20 years development, the limits of
      usefulness of the implant have been established and found to include about one in
      four knees requiring replacement for osteoarthritis. In an independent series,
      using these criteria, the 15 year survival was 94%. Since 1998, the phase 3
      implant has been used with modified instruments through a small incision,
      avoiding damage to the extensor mechanism. Patients now recover about three times
      faster than after TKR, and regain much better flexion (mean 135 degrees ). The
      current evidence supports that the minimally invasive Oxford UKR should be
      seriously considered as primary treatment for anteromedial compartment
      osteoarthritis-provided the appropriate surgical expertise is available.

PMID- 15480546
TI  - Acute renal failure is not a "cute" renal failure!

PMID- 15480548
TI  - Mixed venous blood gas sampling is not influenced by the speed of withdrawal in
      cardiac surgery patients.
AB  - OBJECTIVE: To determine whether mixed venous blood gas sampling obtained by
      pulmonary artery catheter (PAC) is influenced by the speed of withdrawal. DESIGN:
      Prospective, observational study. SETTING: Surgical intensive care unit at a
      university hospital. SUBJECTS: Twenty-five patients in the early postoperative
      period of cardiac surgery. MEASUREMENTS AND MAIN RESULTS: After verification of
      the adequate position of the PAC, measurements of mixed venous blood gas oxygen
      saturation, oxygen partial pressure (PO(2)), carbon dioxide partial pressure
      (PCO(2)), pH and bicarbonates were obtained at two different rates of withdrawal.
      A slow sampling was taken at a mean speed of 3 ml/min and a fast sampling at 18
      ml/min for each patient. The mean difference in venous oxygen saturation between
      slow and fast samplings was -0.18+/-1.3%, venous PO(2): -0.2+/-1.3 mmHg, venous
      PCO(2): 0.1+/-0.9 mmHg, venous pH: 0+/-0.03, venous bicarbonates: 0.03+/-0.5
      mmol/l. CONCLUSION: Using the Bland & Altman method, we showed a satisfactory
      agreement between slow and fast mixed venous blood gas sampling techniques when
      measuring PO(2), oxygen saturation, PCO(2), pH and bicarbonates though a PAC.

PMID- 15480547
TI  - Beneficial effect of low-molecular-weight heparin against lipopolysaccharide
      induced disseminated intravascular coagulation in rats is abolished by
      coadministration of tranexamic acid.
AB  - OBJECTIVE: We examined the role of coagulation and fibrinolysis in
      lipopolysaccharide (LPS) induced disseminated intravascular coagulation (DIC) in
      rats, studying their contribution to fibrin deposition and organ failure in rats
      with LPS-induced DIC by concurrent administration of low molecular weight heparin
      (LMWH) with or without tranexamic acid (TA). METHODS: DIC was induced in male
      Wistar rats by a 4-h infusion of LPS (30 mg/kg) via the tail vein (LPS group). In
      the LPS+LMWH group LMWH (200 u/kg) was administered to rats from 30 min before
      the infusion of LPS for 4.5 h. In the LPS+LMWH+TA group LMWH (200 microg/kg) and
      TA (50 mg/kg) were administered to rats from 30 min before the infusion of LPS
      for 4.5 h. RESULTS: In the LPS+LMWH group lower plasma levels of TAT, D dimer,
      creatinine, and alanine aminotransferase were observed, along with less
      glomerular fibrin deposition and improved survival over rats administered LPS
      alone. However, these effects of LMWH were completely eliminated and damage
      beyond that observed in rats administered LPS alone resulted from combined
      administration of TA (LPS+LMWH+TA group), except that TAT and D dimer levels
      remained lower than in the group administered LPS alone. CONCLUSIONS: Suppression
      of fibrinolysis by TA (despite coadministration of LMWH) resulted in increased
      organ damage in this study, suggesting that depressed fibrinolysis plays a large
      role in organ failure resulting from LPS-induced DIC, even though hemostatic
      activation is moderately suppressed by LMWH.

PMID- 15480550
TI  - European Society of Intensive Care Medicine, 17th Annual Congress. Berlin,
      Germany, 10-13 October 2004. Abstracts.

PMID- 15480549
TI  - Relationship between permeability and luminal concentrations of lactate and
      glycerol in the small intestine?

PMID- 15480562
TI  - Superior vena cava collapsibility as a gauge of volume status in ventilated
      septic patients.

PMID- 15480563
TI  - Sustained moderate reductions in arterial CO2 after brain trauma time-course of
      cerebral blood flow velocity and intracranial pressure.
AB  - OBJECTIVE: In healthy volunteers cerebral blood flow starts to recover towards
      baseline within a few minutes of continued hyperventilation due to normalisation
      of perivascular pH. We investigated the time-course of changes in middle cerebral
      artery mean flow velocity (FVm) and intracranial pressure (ICP) in head-injured
      patients during sustained moderate reductions in arterial partial pressure of
      CO(2) (PaCO(2)). DESIGN: Observational study. PATIENTS: Twenty-seven sedated,
      mechanically ventilated patients with severe head injury. INTERVENTIONS:
      Measurements were made during and after routine determination of CO(2)
      reactivity: an acute 20% increase in respiratory minute volume was followed by a
      10-min stabilisation period and 50 min of continued moderate hyperventilation at
      a constant PaCO(2) (>3.5 kPa). MEASUREMENTS AND RESULTS: FVm was monitored with
      transcranial Doppler, ICP was monitored with intraparenchymal probes. During the
      50-min period with stable PaCO(2) FVm increased in 36% of patients. All other
      patients showed a decline in FVm over the same time period. Overall FVm recovery
      was -0.03+/-0.14%.min(-1). The time-course of ICP changes was significantly
      different from that of FVm, with ICP reaching its lowest value earlier than FVm
      (23+/-12 vs 37+/-20 min; P = 0.001) and returning more rapidly towards baseline
      than FVm (0.23+/-0.23 vs -0.03+/-0.14%.min(-1); P< 0.0001). CONCLUSIONS: Head
      injured patients may adapt differently to hyperventilation than healthy
      volunteers. Potentially harmful reductions in cerebral blood flow may persist
      beyond the duration of useful ICP reduction.

PMID- 15480564
TI  - Changes in lung volume with three systems of endotracheal suctioning with and
      without pre-oxygenation in patients with mild-to-moderate lung failure.
AB  - OBJECTIVE: To compare changes in lung volume, oxygenation, airway pressure, and
      hemodynamic effects induced by suctioning with three systems in critically ill
      patients with mild-to-moderate lung disease, and also to evaluate the effects of
      hyperoxygenation applied prior to the maneuver as suggested by some guidelines.
      DESIGN: Prospective crossover study. SETTING: General intensive care department
      of a university-affiliated hospital. PATIENTS: Ten mechanically ventilated
      patients with mild-to-moderate acute respiratory failure. INTERVENTIONS: Patients
      were ventilated in volume control mode with a mean tidal volume of 490+/-88 ml,
      PEEP 7+/-4 cmH2O and FiO(2) 0.36+/-0.05. Suctioning was performed sequentially
      with a quasi-closed system, with an open system 10 min later, and finally with a
      closed system. Thereafter, pure oxygen was applied for 2 min and the whole
      suctioning sequence was repeated in reverse order. MEASUREMENTS AND MAIN RESULTS:
      Patients' mean PaO(2)/FiO(2) ratio was 273+/-28 mmHg. The reductions in lung
      volume during suctioning were similar with the quasi-closed (386+/-124 ml) and
      closed system (497+/-338 ml), but significantly higher with the open system
      (1281+/-656 ml, P=0.022). We found no significant hemodynamic adverse effects,
      and no significant SpO(2) reductions with all the studied suctioning techniques.
      Pre-oxygenation with pure oxygen did not induce additive effects in lung volume
      changes. With and without pre-oxygenation, lung volume returned to baseline in
      every patient within 10 min. CONCLUSIONS: Suctioning with closed and quasi-closed
      systems reduces the substantial losses in lung volume observed with the open
      system. Nevertheless, in patients without severe lung disease these changes were
      transient and rapidly reversible.

PMID- 15480565
TI  - Post mortem examination in the intensive care unit: still useful?
AB  - OBJECTIVE: Post mortem examination rates have decreased worldwide and their
      usefulness has been challenged. The aim of this study was to compare ante- versus
      post mortem findings in a multidisciplinary ICU. DESIGN: Retrospective study.
      SETTING: Thirty-one-bed, medico-surgical ICU. PATIENTS: All patients who died on
      the ICU and underwent an autopsy examination in 1999. MEASUREMENTS: Records from
      autopsies were compared with clinical records. A modified Goldman's criteria was
      used to categorize the post mortem diagnoses. Unexpected findings were evaluated
      according to the duration of hospitalization prior to death (fewer than or more
      than 10 days). RESULTS: Among 2,984 ICU admissions, there were 489 deaths; 222
      autopsies were conducted (45.4% autopsy rate). Post mortem examination revealed
      unexpected findings in 50 patients (22.5%), including malignancy (22 [9.9%]),
      fungal infections (9 [4%]), pulmonary embolism (7 [3.2%]), nosocomial infections
      (3 [1.3%]), Hashimoto's disease (3 [1.3%]), mesenteric infarction (2 [0.9%]),
      Barrett's esophagus (2 [0.9%]), endocarditis (1 [0.5%]) and myocardial infarction
      (1 [0.5%]). These unexpected findings were considered as major (Class I/II) in 19
      (8.5%), and minor (Class III) in 31 (14%) patients. In patients with a short ICU
      length of stay (<10 days), there were more major unexpected findings than minor,
      while after a prolonged stay (>10 days), minor unexpected findings were more
      common. CONCLUSIONS: After a short ICU stay (<10 days), autopsy revealed
      discrepancies primarily related to the cause of death associated with diseases
      whose diagnosis can be difficult. Following more prolonged ICU stays (>10 days),
      autopsy was more likely to reveal coexisting diseases unrelated to death.

PMID- 15480566
TI  - Renal transplantation in patients with abdominal aortic aneurysm--a new surgical
      approach.
AB  - An increasing number of abdominal aortic aneurysms occurs in renal failure
      patients because of an accelerated atherosclerosis process associated with
      uraemia. When technically feasible, endovascular repair of an abdominal aortic
      lesion should be considered as the treatment of choice. If a surgical repair is
      suggested, there are several options to select from. Since November 1999, we
      performed simultaneous aortic reconstruction using fresh arterial allograft and
      kidney transplantation in five uraemic patients with asymptomatic abdominal
      aortic aneurysm. The operative and postoperative course of four patients passed
      without major complications. One patient had ischaemic colitis early after the
      operation, which required a partial resection of the colon. One patient died 6
      weeks after the operation due to non-vascular causes. In conclusion, the
      advantage of our single-phase procedure is that both diseases are treated
      simultaneously during a single hospital stay. Moreover, with our procedure, the
      risk of vascular graft infection in patients with chronic immunosuppression is
      low.

PMID- 15480570
TI  - Which sling for which patient?

PMID- 15480571
TI  - Prevention of vertebral fractures by strontium ranelate in postmenopausal women
      with osteoporosis.
AB  - The antifracture efficacy of strontium ranelate, a compound with a novel
      mechanism of action on bone, has been assessed in two large, randomized,
      controlled trials conducted in postmenopausal women. Strontium ranelate was given
      at a daily dose of 2 g, and all women received calcium and vitamin D supplements.
      In women with established osteoporosis there was a 41% reduction in vertebral
      fractures over 3 years' treatment [relative risk (RR) 0.59; 95% confidence
      interval (CI) 0.48-0.73; P<0.001]; significant reductions were also seen after
      only 1 year of treatment. The beneficial effect was also seen for clinical
      vertebral fractures: over 3 years there was a significant reduction in new
      clinical vertebral fractures (RR 0.62; 95% CI 0.47-0.83; P<0.001); this reduction
      was also observed during the first year of treatment (RR 0.48; 95% CI 0.29-0.80;
      P=0.003). Over the 3-year treatment period significantly fewer patients had
      height loss and fewer patients reported new or worsening back pain in the treated
      group than in the control group. These results demonstrate that strontium
      ranelate is a new therapeutic option in the prevention of osteoporotic vertebral
      fractures in postmenopausal women.

PMID- 15480572
TI  - Impact of vertebral deformities, osteoarthritis, and other chronic diseases on
      quality of life: a population-based study.
AB  - Vertebral deformities and spinal osteoarthritis are common disorders in elderly
      persons and are associated with back pain, impaired physical functioning, and
      loss of quality of life. The objectives of this study were to assess the impact
      of vertebral deformities and osteoarthritis on quality of life in a population
      based sample, and to compare this with the impact of six other important chronic
      diseases on quality of life. The study was performed as a substudy of the
      Longitudinal Aging Study Amsterdam. Vertebral deformities and osteoarthritis were
      assessed by spinal radiographs; chronic diseases were assessed by self-report;
      quality of life was estimated by the SF-12, EQ-5D (EuroQol) and Qualeffo-41 (n =
      336). In univariate analyses, severe osteoporosis of the vertebrae significantly
      worsened the physical component summary scale of the SF-12 and the total score of
      Qualeffo-41, while osteoarthritis of the spine did not significantly reduce
      quality of life. The other chronic diseases reduced quality of life, although not
      all changes reached statistical significance. In multivariate analyses, severe
      osteoporosis of the vertebrae, cardiac disease, peripheral arterial disease, and
      diabetes mellitus significantly reduced quality of life. In conclusion, most
      persons in an elderly population suffer from one or more chronic diseases, and
      therefore experience loss of quality of life. After adjustment for age, sex, and
      other chronic diseases, severe osteoporosis of the vertebrae, cardiac disease,
      peripheral arterial disease, and diabetes mellitus significantly reduced quality
      of life in the general population.

PMID- 15480573
TI  - Calcaneum broadband ultrasound attenuation relates to vegetarian and omnivorous
      diets differently in men and women: an observation from the European Prospective
      Investigation into Cancer in Norfolk (EPIC-Norfolk) population study.
AB  - Vegetarian diets have been suggested to be beneficial for bone health due to
      increased consumption of plant foods, including soya, or reduced consumption of
      meat. However, meat may also be beneficial for bone health. The evidence relating
      diet to bone health is based largely on studies of women, often in those at high
      risk of osteoporosis. Few studies have investigated dietary inter-relationships
      in men as well as women from general populations. We examined broadband
      ultrasound attenuation (BUA) of the calcaneum, using a CUBA clinical instrument,
      in 6,369 men and 5,379 postmenopausal women. The population was divided into four
      groups according to vegetarian status and frequency of soya consumption, which
      was defined by response to a food frequency questionnaire that estimates
      frequency of consumption of food types over the year prior to completion. Regular
      soya consumers were defined as those who ate soya products with a frequency of
      between once a day and once a week. Calcaneum BUA in vegetarian men was
      significantly lower than omnivores by approximately 6% (5 dB/MHz) and was 15%
      (13.6 dB/MHz) lower in those who were also regular soya consumers. This
      difference remained after adjustment for age, height, weight, smoking habit,
      physical activity, selected foods and nutrients and exclusion of those with a
      prior history of osteoporosis, fractures or cancer. Calcaneum BUA in omnivorous
      men with regular soya consumption was not lower than the remaining population. In
      women, there were no significant differences by usual dietary pattern. This
      surprising finding indicates that regular soya intake is not associated with
      better bone indices in vegetarian men. The difference in BUA was not explained by
      the known common covariates; however, it is possible that other aspects of
      lifestyle associated with these eating behaviors might explain this observation.
      Plausible mechanisms exist for our findings; soya contains phytoestrogens,
      likened to naturally occurring estrogens, and meat has been shown to influence
      levels of IGF-1 and sex hormone binding globulin, which may be related to bone
      health. Our findings emphasize the need for further research and investigation
      into dietary inter-relationships and bone health and the effects of vegetarian
      status, including consumption of soya-based foods, in men as well as women.

PMID- 15480574
TI  - The glycosylated cell surface protein Rpf2, containing a resuscitation-promoting
      factor motif, is involved in intercellular communication of Corynebacterium
      glutamicum.
AB  - The genome of Corynebacterium glutamicum ATCC 13032 contains two genes, rpf1 and
      rpf2, encoding proteins with similarities to the essential resuscitation
      promoting factor (Rpf) of Micrococcus luteus. Both the Rpf1 (20.4 kDa) and Rpf2
      (40.3 kDa) proteins share the so-called Rpf motif, a highly conserved protein
      domain of approximately 70 amino acids, which is also present in Rpf-like
      proteins of other gram-positive bacteria with a high G+C content of the
      chromosomal DNA. Purification of the C. glutamicum Rpf2 protein from concentrated
      supernatants, SDS-PAGE and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry identified modified Rpf2 variants with increased or
      reduced mobility when compared with the calculated size of Rpf2. A Western blot
      based enzyme immunoassay demonstrated glycosylation of the Rpf2 variants with
      higher molecular masses. Galactose and mannose were identified as two components
      of the oligosaccharide portion of the Rpf2 glycoprotein by capillary gas
      chromatography coupled to mass spectrometry. The Rpf2 protein was localized on
      the surface of C. glutamicum with the use of immuno-fluorescence microscopy. C.
      glutamicum strains with defined deletions in the rpf1 or rpf2 gene or
      simultaneous deletions in both rpf genes were constructed, indicating that the
      rpf genes are neither individually nor collectively essential for C. glutamicum.
      The C. glutamicum rpf double mutant displayed slower growth and a prolonged lag
      phase after transfer of long-stored cells into fresh medium. The addition of
      supernatant from exponentially growing cultures of the rpf double mutant, the
      wild type or C. glutamicum strains with increased expression of the rpf1 or rpf2
      gene significantly reduced the lag phase of long-stored wild-type and rpf single
      mutant strains, but addition of purified His-tagged Rpf1 or Rpf2 did not. In
      contrast, the lag phase of the C. glutamicum rpf double mutant was not affected
      upon addition of these culture supernatants.

PMID- 15480575
TI  - Heterologous overexpression of quorum-sensing regulators to study cell-density
      dependent phenotypes in a symbiotic plant bacterium Mesorhizobium huakuii.
AB  - Quorum-sensing is widespread among many prokaryotic lineages. In order to
      investigate quorum regulation in the plant bacterium Mesorhizobium huakuii which
      produces an N-acyl homoserine lactone (AHL) quorum signal, the Agrobacterium
      quorum-sensing regulator TraR was heterologously expressed in this bacterium. The
      resulting strains showed reduced AHL production in the supernatant compared to
      wild-type, but similar intracellular levels of AHLs were detected, suggesting
      that M. huakuii AHLs can be bound to intracellular TraR proteins and thus become
      unavailable for its own quorum systems. M. huakuii overexpressing TraR formed
      thinner biofilms than the wild-type, suggesting a role played by quorum-sensing
      in biofilm formation.

PMID- 15480576
TI  - Relations and functions of dye-linked formaldehyde dehydrogenase from
      Hyphomicrobium zavarzinii revealed by sequence determination and analysis.
AB  - faoA, the gene of the dye-linked NAD(P)-independent quinone-containing
      formaldehyde dehydrogenase of methylamine-grown Hyphomicrobium zavarzinii strain
      ZV 580 was sequenced and analyzed together with an apparent promoter region and
      adjoining genes in a 7.2-kb fragment of hyphomicrobial DNA. The formaldehyde
      dehydrogenase, identified as a periplasmic enzyme by its signal sequence, is
      distantly related to the soluble pyrroloquinoline-quinone-dependent glucose
      dehydrogenase of Acinetobacter calcoaceticus and to other predicted glucose
      dehydrogenase sequences. The promoter region, containing about 400 nucleotides
      upstream of faoA, comprised potential binding sites identical or highly similar
      to known consensus sequences of the sigma factors sigma(70) (housekeeping),
      sigma(H) (heat shock), sigma(F) (flagellar) and sigma(N) (nitrogen). The complex
      regulation of the transcription of faoA, which is suggested by this setting and
      emphasized by a possible heat-shock promoter, supports a hypothesis proposing an
      auxiliary role of the enzyme in lowering detrimental elevated concentrations of
      formaldehyde, which might arise in the course of stress or regulatory transitions
      disturbing balanced C(1) metabolism.

PMID- 15480577
TI  - New CCK2 agonists confirming the heterogeneity of CCK2 receptors:
      characterisation of BBL454.
AB  - Pharmacological studies were undertaken with a new series of cholecystokinin(2)
      CCK(2) agonists in order to assign to them a CCK(2A) or CCK(2B) pharmacological
      profile. The open-field test was chosen as the discrimination test of CCK(2B)
      agonists. The most interesting agonist, BBL454 (0.03-300 microg/kg) induced
      hyperactivity which was blocked by a CCK(2) antagonist, the D1 antagonist
      SCH23390, the delta-opioid antagonist naltrindole, but not a CCK(1) antagonist.
      All compounds active in the open-field test are characterised by a common
      structural feature, -COCH(2)CO-Trp-NMeNle-Asp-Phe-NH(2), whereas inactive
      compounds do not possess such a motive. Therefore, this feature can be considered
      crucial for CCK(2B) activity. BBL454 (0.03-3 microg/kg) improved memory in a two
      trial memory test while it was very weakly active on the peripheral CCK(2)
      receptor, and did not evoke anxiogenic effects in the plus-maze test. The
      synthesis of BBL454 is simple, its minimal active dose is 30 ng/kg and no "bell
      shaped" responses were observed. These results suggest that BBL454 could be
      considered to be the new CCK(2B) reference agonist.

PMID- 15480578
TI  - Evidence for the role of nitric oxide in nicotine-induced locomotor sensitization
      in mice.
AB  - RATIONALE: Nitric oxide (NO) is implicated in both acute effects of addictive
      drugs and development of dependence to them. We investigated the role of NO in
      nicotine-induced locomotor sensitization. OBJECTIVES: The effects of Nomega-nitro
      L-arginine methyl ester (L-NAME), a NO synthase inhibitor, and a combination of a
      NO precursor L-arginine and L-NAME on nicotine-induced locomotor sensitization
      were investigated in Swiss Webster mice. METHODS: Sensitization to psychomotor
      stimulating effect of nicotine was rendered by seven injections of nicotine (1
      mg/kg) on every other day. To investigate their effect on the development of
      sensitization to nicotine, L-NAME (15-60 mg/kg) and L-arginine (1 g/kg) were
      given before nicotine administration during the first seven sessions. To
      investigate the effect of these compounds on the expression of nicotine
      sensitization, after a 4-day drug-free period another group of mice received a
      challenge injection of nicotine on day 18. RESULTS: Nicotine (1 mg/kg) produced a
      robust locomotor sensitization in mice. The doses of 30 mg/kg and 60 mg/kg of L
      NAME blocked the development of sensitization to nicotine; and, L-arginine (1
      g/kg) pretreatment reversed this effect of L-NAME. Likewise, the doses of 30
      mg/kg and 60 mg/kg of L-NAME inhibited the expression of sensitization to
      nicotine on day 18; and, L-arginine (1 g/kg) pretreatment reversed this
      inhibitory effect of L-NAME. CONCLUSIONS: Our results suggest that NO is
      implicated in the development and expression of nicotine-induced locomotor
      sensitization in mice.

PMID- 15480579
TI  - Efficient and rapid method for extraction of intact phospholipids from sediments
      combined with molecular structure elucidation using LC-ESI-MS-MS analysis.
AB  - This paper presents the application of an efficient method for extraction and
      fractionation of intact phospholipids (PLs) from complex sediment matrices and
      elucidation of their molecular structure by normal-phase HPLC-ESI-MS-MS. Flow
      blending extraction was tested with different solvent mixtures and the best
      recovery of all PLs classes from the sediment matrix was achieved by using
      methanol-dichloromethane-buffer, 2:1:0.8. The applied LC-ESI-MS system has
      linearity of R2=0.98 and a detection limit of 0.5 ng/PL, sufficient for reliable
      identification of complex mixtures of PLs. MS-MS analyses using a triple
      quadrupole mass spectrometer enables detection of individual PL side-chain
      composition and, hence, characterization of the living organisms contributing to
      the sedimentary organic material. Parallel GC-MS analysis of the hydrolysed
      phospholipid fatty acids supports the characterized fatty acid patterns
      determined from intact PLs. The PL inventory of different investigated lacustrine
      surface sediments shows predominantly high abundance of phosphatidylglycerols and
      phosphatidylethanolamines and phosphatidyl-mono- and dimethyl-ethanolamines with
      fatty acyl side-chains typically known from bacteria. In a sample from Lake
      Baikal intense signals of bacterial 14:0-acyl-PGs were also identified, for the
      first time in sediments as far as we are aware.

PMID- 15480581
TI  - Molecular imprinting: a dynamic technique for diverse applications in analytical
      chemistry.
AB  - Continuous advances in analyzing complex matrices, improving reliability and
      simplicity, and performing multiple simultaneous assays with extreme sensitivity
      are increasing. Several techniques have been developed for the quantitative
      assays of analytes at low concentrations (e.g., high-pressure liquid
      chromatography, gas chromatography, immunoassay and the polymerase chain reaction
      technique). To achieve highly specific and sensitive analysis, high affinity,
      stable, and specific recognition agents are needed. Although biological
      recognition agents are very specific and sensitive they are labile and/or have a
      low density of binding sites. During the past decade molecular imprinting has
      emerged as an attractive and highly accepted tool for the development of
      artificial recognition agents. Molecular imprinting is achieved by the
      interaction, either noncovalent or covalent, between complementary groups in a
      template molecule and functional monomer units through polymerization or
      polycondensation. These molecularly imprinted polymers have been widely employed
      for diverse applications (e.g., in chromatographic separation, drug screening,
      chemosensors, catalysis, immunoassays etc.) owing to their specificity towards
      the target molecules and high stability against physicochemical perturbations. In
      this review the advantages, applications, and recent developments in molecular
      imprinting technology are highlighted.

PMID- 15480582
TI  - Time-resolved enzymatic determination of glucose using a fluorescent europium
      probe for hydrogen peroxide.
AB  - An enzymatic assay for glucose based on the use of the fluorescent probe for
      hydrogen peroxide, europium(III) tetracycline (EuTc), is described. The weakly
      fluorescent EuTc and enzymatically generated H2O2 form a strongly fluorescent
      complex (EuTc-H2O2) whose fluorescence decay profile is significantly different.
      Since the decay time of EuTc-H2O2 is in the microseconds time domain,
      fluorescence can be detected in the time-resolved mode, thus enabling substantial
      reduction of background fluorescence. The scheme represents the first H2O2-based
      time-resolved fluorescence assay for glucose not requiring the presence of a
      peroxidase. The time-resolved assay (with a delay time of 60 micros and using
      endpoint detection) enables glucose to be determined at levels as low as 2.2
      micromol L(-1), with a dynamic range of 2.2-100 micromol L(-1). The method also
      was adapted to a kinetic assay in order to cover higher glucose levels (mmol L(
      1) range). The latter was validated by analyzing spiked serum samples and gave a
      good linear relationship for glucose levels from 2.5 to 55.5 mmol L(-1).
      Noteworthy features of the assay include easy accessibility of the probe, large
      Stokes' shift, a line-like fluorescence peaking at 616 nm, stability towards
      oxygen, a working pH of approximately 7, and its suitability for both kinetic and
      endpoint determination.

PMID- 15480583
TI  - 1H high-resolution magic-angle spinning (HR-MAS) NMR analysis of ligand density
      on resins using a resin internal standard.
AB  - We recently attempted to generate an affinity chromatography adsorbent to purify
      cytochrome P450 4A1 by coupling 11-(1'-imidazolyl)-3,6,9-trioxaundecanoic acid to
      Toyopearl AF-Amino 650 M resin. Variations in ligand density for several resin
      batches were quantified by high-resolution magic-angle spinning (HR-MAS) NMR
      spectroscopy using a novel resin internal standard. The uniquely designed ImQ
      internal resin standard yields its signature resonance in a transparent region of
      the analyte spectrum making suppression of the polymer background unnecessary.
      This method enabled us to target a reasonable ligand density for enzyme
      purification and provides an advantageous alternative to quantitation against
      soluble standards or protonated solvent.

PMID- 15480584
TI  - Technology of production of red figure pottery from Attic and southern Italian
      workshops.
AB  - Samples from Greek figure vases were investigated by scanning electron microscopy
      coupled with energy dispersive X-ray analysis, X-ray diffraction,
      thermomechanical analysis and reflectance spectroscopy to achieve a technological
      characterisation. The vases, dating from the end of the sixth to the fourth
      century BC, had been excavated at Locri Epizephiri (Calabria, Italy) and
      attributed to Attic or local workshops, respectively. Information on the
      morphology of black slip areas and firing temperatures was compared with that
      previously obtained for Attic and local black gloss pottery from the same site;
      results show that the peculiar technique required for the production of black
      slips was mastered by both Attic and local potters and employed for monochrome
      and figured products. The black coating is usually well vitrified and 15- to 20
      microm thick; the evaluated maximum firing temperature is around 900 degrees C,
      while a temperature lower than 800 degrees C is generally estimated for ceramic
      body re-oxidation.

PMID- 15480585
TI  - Facilitated transport of Hg(II) through novel activated composite membranes.
AB  - The results presented in this work deal with the prime application of activated
      composite membranes (ACMs) for the transport of Hg(II) ions in a continuous
      extraction-re-extraction system using di-(2-ethylhexyl)dithiophosphoric acid
      (DTPA) as carrier. The effects of variables such as the pH, the nature of the
      acid and the concentration of the casting solutions on the transport of Hg(II)
      are also investigated. When the ACM was prepared with a 0.5 M DTPA solution and
      when the feed solution contained 2.5x10(-4) M Hg(II) in 0.1 M HCl, the amount of
      mercury extracted was greater than 76%. The re-extracted mercury was subsequently
      recovered by means of a stripping phase comprising 0.3 M thiourea solution in 2 M
      H2SO4, yielding 54% of the initial amount of mercury after transport had taken
      place for 180 min.

PMID- 15480587
TI  - Deficits in adaptive upper limb control in response to trunk perturbations in
      Parkinson's disease.
AB  - The ability of patients with Parkinson's disease (PD) to compensate for
      unexpected perturbations remains relatively unexplored. To address this issue PD
      subjects were required to compensate at the arm for an unexpected mechanical
      perturbation of the trunk while performing a trunk-assisted reach. Twelve healthy
      and nine PD subjects (off medication) performed trunk-assisted reaching movements
      without vision or knowledge of results to a remembered target in the ipsilateral
      (T1) or contralateral (T2) workspace. On 60% of the trials trunk motion was
      unrestrained (free condition). On the remaining 40% of randomly selected trials
      trunk motion was arrested at movement onset (blocked condition). If subjects
      appropriately changed arm joint angles to compensate for the trunk arrest, there
      should be spatial and temporal invariance in the hand trajectories and in the
      endpoint errors across conditions. The control group successfully changed their
      arm configuration in a context-dependent manner which resulted in invariant hand
      trajectory profiles across the free and blocked conditions. More so, they
      initiated these changes rapidly after the trunk perturbation (group mean 70 ms).
      Some PD subjects were unable to maintain invariant hand paths and movement errors
      across conditions. Their hand velocity profiles were also more variable relative
      to those of the healthy subjects in the blocked-trunk trials but not in the free
      trunk trials. Furthermore, the latency of compensatory changes in arm joint
      angles in movements toward T1 was longer in the PD group (group mean 153 ms).
      Finally, PD subjects' arm and trunk were desynchronized at movement onset,
      confirming our previous findings and consistent with PD patients' known problems
      in the sequential or parallel generation of different movement components. The
      findings that individual PD subjects were unsuccessful or delayed in producing
      context-dependent responses at the arm to unexpected perturbations of the trunk
      suggests that the basal ganglia are important nodes in the organization of
      adaptive behavior.

PMID- 15480586
TI  - Frontal and central oscillatory changes related to different aspects of the motor
      process: a study in go/no-go paradigms.
AB  - We studied alpha and beta EEG oscillatory changes in healthy volunteers during
      two different auditory go/no-go paradigms, in order to investigate their
      relationship with different components of the motor process. In the first
      paradigm (S2-centered), the initial tone (S1) was constant (warning), and the
      second tone (S2) indicated the subject whether to move or not. In the second
      paradigm (S1-centered), S1 indicated whether to move or not, while S2 just
      indicated the timing of the movement. A medial frontal beta energy increase was
      found in all conditions after the stimulus that forces the subject to decide
      whether to move or not (S1 or S2 depending on the paradigm). In both go
      conditions, a central alpha and beta energy decrease began after the go decision,
      reaching minimum values during the movement; it was followed by a beta post
      movement increase, limited to the central contralateral area. In the no-go
      conditions, a marked fronto-central beta synchronization appeared after the
      decision not to move. In conclusion, our study was able to dissociate the beta
      oscillatory changes related to movement preparation and execution (central
      decrease/increase) from those associated with decision-making (medial frontal
      increase) and motor inhibition (fronto-central increase).

PMID- 15480588
TI  - Is there a timing synergy during multi-finger production of quick force pulses?
AB  - We studied whether characteristics of individual finger force profiles covaried
      across repetitions of a quick force pulse production task to stabilize the
      required magnitude and timing of the peak force. Subjects produced series of
      quick force pulses by pressing with all four fingers of the right hand on force
      sensors under the instruction to keep the magnitude of the peak of total force at
      15 N and reach the force peaks at prescribed times. Individual finger force
      pulses were then reshuffled across trials to create a surrogate data set. The
      surrogate data set showed a lower average peak force with a larger dispersion.
      This finding has been interpreted as pointing at predominantly negative
      covariation among finger force pulses in the actual data that stabilized the
      required magnitude of the total force, a force synergy. The difference between
      the actual and surrogate data sets was significant early into the pulse time,
      starting about 40 ms after the pulse initiation. This finding points at a central
      nature of the negative covariation without a major role played by visual or
      proprioceptive feedback. In contrast, the surrogate data set showed smaller
      dispersion of the timing of the total peak force, suggesting positive covariation
      of the timings of individual finger force pulses in the actual data interpreted
      as the lack of a timing synergy. These results have been confirmed with principal
      component (PC) analysis. The first PC for the timing of the individual finger
      peak forces accounted for over 90% of the total variance for the actual data set
      and for under 40% of the total variance for the surrogate data set. The fourth PC
      for the magnitudes of the finger forces accounted for under 4% of the total
      variance for the actual data set and for over 15% of the variance for the
      surrogate data set. The data are interpreted within the uncontrolled manifold
      hypothesis; they support the hierarchical control scheme suggested by Schoner.

PMID- 15480589
TI  - Incidental information acquired by the amygdala during acquisition of a stimulus
      response habit task.
AB  - In the present paper we tested the hypothesis that the amygdala incidentally
      acquires information during the acquisition of a task sensitive to damage to the
      dorso-lateral striatum. Two groups of rats were trained on a stimulus-response (S
      R) habit task on the eight-arm radial maze. Prior to initial acquisition, one
      group received NMDA lesions of the amygdala and the other received sham
      surgeries. After reaching a strict learning criterion, both groups underwent
      reversal training in either the same or different context from original training.
      Consistent with our previous work, the sham group showed enhanced reversal
      learning in a context different from original training. The rats with amygdala
      damage showed a deficit in reversal learning in both contexts, although the
      deficit was more apparent in the different context. Both groups of rats that
      underwent reversal training in the context different from original training
      showed a normal competition effect for this task (chance performance) when they
      were returned to the initial training context. This data supports the idea that
      the second S-R association, acquired during reversal training, and the context
      specific inhibitory association, acquired during original training, were
      unaffected by the amygdala damage. Taken together, this pattern of data suggests
      that the amygdala incidentally acquired information during the acquisition of the
      S-R habit task. The nature of the association acquired in this learning paradigm,
      and the implications of this finding for theories dealing with the organization
      and functions of mammalian learning and memory are discussed.

PMID- 15480590
TI  - The relationship of saccadic peak velocity to latency: evidence for a new
      prosaccadic abnormality in schizophrenia.
AB  - Antisaccades have not only longer latencies but also lower peak velocities than
      prosaccades. It is not known whether these latency and velocity differences are
      related. Studies of non-human primates suggest that prosaccade peak velocity
      declines as latency from target appearance increases. We examined whether a
      similar relationship between peak velocity and latency existed in human saccades,
      whether it accounted for the difference in peak velocity between antisaccades and
      prosaccades, and whether it was affected by schizophrenia, a condition that
      affects antisaccade performance. Sixteen control and 21 schizophrenia subjects
      performed prosaccade and antisaccade trials in the same test session. In both
      groups antisaccades had lower peak velocities than prosaccades. Latency did not
      influence the peak velocities of antisaccades in either subject group. At short
      latencies, the peak velocities of prosaccades were also similar in the two
      groups. However, while prosaccade peak velocities declined minimally with
      increasing latency in control subjects, those in the schizophrenia group declined
      significantly until they reached a value similar to antisaccade peak velocities.
      We conclude that, in normal subjects, the effect of latency on prosaccade peak
      velocity is minimal and cannot account for the lower velocity of antisaccades. In
      schizophrenia, we hypothesize that the latency-related decline in prosaccade peak
      velocity may reflect either an increased rate of decay of the effect of the
      transient visual signal at the saccadic goal, or a failure of the continuing
      presence of the target to sustain neural activity in the saccadic system.

PMID- 15480591
TI  - Inhibition of return in microsaccades.
AB  - Inhibition of return (IOR) is the term used to describe the phenomenon whereby
      stimuli appearing at recently attended locations are reacted to less efficiently
      than stimuli appearing at locations that have not yet been attended. In the
      present study, we employed a typical IOR paradigm with peripheral uninformative
      cues while participants maintained their eyes at fixation. Eye position was
      monitored at a high sampling rate (500 Hz) in order to detect miniature eye
      movements called microsaccades, which have been shown to be crucial for avoiding
      disappearance of visual image. However, recent studies have demonstrated a close
      relationship between covert endogenous attentional shifts and the direction of
      microsaccades. Here, we demonstrate that the direction of microsaccades can be
      biased away from the peripheral location occupied by a salient, although task
      irrelevant, visual signal. Because microsaccades are known not to be under
      conscious control, our results suggest strong links between IOR and unconscious
      oculomotor programming.

PMID- 15480593
TI  - Facilitation of soleus H-reflex amplitude evoked by cutaneous nerve stimulation
      at the wrist is not suppressed by rhythmic arm movement.
AB  - Neural connections between the cervical and lumbosacral spinal cord may assist in
      arm and leg coordination during locomotion. Currently the extent to which arm
      activity can modulate reflex excitability of leg muscles is not fully understood.
      We showed recently that rhythmic arm movement significantly suppresses soleus H
      reflex amplitude probably via modification of presynaptic inhibition of the IA
      afferent pathway. Further, during walking reflexes evoked in leg muscles by
      stimulation of a cutaneous nerve at the wrist (superficial radial nerve; SR) are
      phase and task dependent. However, during walking both the arms and legs are
      rhythmically active thus it is difficult to identify the locus of such
      modulation. Here we examined the influence of SR nerve stimulation on
      transmission through the soleus H-reflex pathway in the leg during static
      contractions and during rhythmic arm movements. Nerve stimulation was delivered
      with the right shoulder in flexion or extension. H-reflexes were evoked alone
      (unconditioned) or with cutaneous conditioning via stimulation of the SR nerve
      (also delivered alone without H-reflex in separate trials). SR nerve stimulation
      significantly facilitated H-reflex amplitude during static contractions with the
      arm extended and countered the suppression of reflex amplitude induced by arm
      cycling. The results demonstrate that cutaneous feedback from the hand on to the
      soleus H-reflex pathway in the legs is not suppressed during rhythmic arm
      movement. This contrasts with the observation that rhythmic arm movement
      suppresses facilitation of soleus H-reflex when cutaneous nerves innervating the
      leg are stimulated. In conjunction with other data taken during walking, this
      suggests that the modulation of transmission through pathways from the SR nerve
      to the lumbosacral spinal cord is partly determined by rhythmic activity of both
      the arms and legs.

PMID- 15480592
TI  - Actual and mental motor preparation and execution: a spatiotemporal ERP study.
AB  - Studies evaluating the role of the executive motor system in motor imagery came
      to a general agreement in favour of the activation of the primary motor area (M1)
      during imagery, although in reduced proportion as compared to motor execution. It
      is still unclear whether this difference occurs within the preparation period or
      the execution period of the movement, or both. In the present study, EEG was used
      to investigate separately the preparation and the execution periods of overt and
      covert movements in adults. We designed a paradigm that randomly mixed actual and
      kinaesthetic imagined trials of an externally paced sequence of finger key
      presses. Sixty channel event-related potentials were recorded to capture the
      cerebral activations underlying the preparation for motor execution and motor
      imagery, as well as cerebral activations implied in motor execution and motor
      imagery. Classical waveform analysis was combined with data-driven spatiotemporal
      segmentation analysis. In addition, a LAURA source localization algorithm was
      applied to functionally define brain related motor areas. Our results showed
      first that the difference between actual and mental motor acts takes place at the
      late stage of the preparation period and consists of a quantitative modulation of
      the activity of common structures in M1. Second, they showed that primary motor
      structures are involved to the same extent in the actual or imagined execution of
      a motor act. These findings reinforce and refine the functional equivalence
      hypothesis between actual and imagined motor acts.

PMID- 15480594
TI  - Effect of human grip strategy on force control in precision tasks.
AB  - Alternate grip strategies are often used for object manipulation in individuals
      with sensorimotor deficits. To determine the effect of grip type on force
      control, ten healthy adult subjects were asked to grip and lift a small
      manipulandum using a traditional precision grip (lateral pinch), a pinch grip
      with the fingers oriented downwards (downward pinch) and a "key grip" between the
      thumb and the side of the index finger. The sequence of grip type and hand used
      was varied randomly after every ten lifts. Each of the three grips resulted in
      different levels of force, with the key grip strategy resulting in the greatest
      grip force and the downward pinch grip using the least amount of grip force to
      lift the device. Cross-correlation analysis revealed that the ability to scale
      accurately the rate of grip force and load force changes was lowest in the
      downward pinch grip. This was also associated with a more variable time-shift
      between the two forces, indicating that the precise anticipatory control when
      lifting an object is diminished in this grip strategy. There was a difference
      between hands across all grips, with the left non-dominant hand using greater
      grip force during the lift but not the hold phase. Further, in contrast with the
      right hand, the left hand did not reduce grip force during the lift or the hold
      phase over the ten lifts, suggesting that the non-dominant hand did not quickly
      learn to optimise grip force. These findings suggest that the alternate grip
      strategies used by patients with limited fine motor control, such as following
      stroke, may partly explain the disruption of force control during object
      manipulation.

PMID- 15480595
TI  - Long-term restoration of nigrostriatal system function by implanting GDNF
      genetically modified fibroblasts in a rat model of Parkinson's disease.
AB  - The motor behavior and levels of dopamine and its metabolites in the striatum
      were studied in rats that received a unilateral injection of 6-OHDA and underwent
      grafting of rat-derived primary fibroblasts that had been genetically modified to
      express lacZ and human glial cell line-derived neurotrophic factor (GDNF).
      Rotation behavior tests were performed each week and striatal levels of DA and
      its metabolites were measured every 4 weeks after grafting of fibroblasts that
      expressed lacZ, with or without additional transfection of the GDNF transgene.
      Rats grafted with GDNF-producing fibroblasts showed a significant improvement in
      motor behavior as determined by the rotation test, with a less pronounced
      reduction in the levels of dopamine and its metabolites in the striatum as
      compared with those in the control animals or brain parts. In addition, there was
      a lower decrease in the number of TH immunoreactive neurons in the substantia
      nigra ipsilateral to the lesion in rats with GDNF-producing fibroblasts than in
      rats with lacZ-expressing fibroblasts. These results support the notion that
      intracerebral grafting of fibroblasts that express GDNF is a potentially useful
      therapeutic strategy for treating Parkinson's disease.

PMID- 15480596
TI  - Acquisition and generalization of visuomotor transformations by nonhuman
      primates.
AB  - The kinematics of straight reaching movements can be specified vectorially by the
      direction of the movement and its extent. To explore the representation in the
      brain of these two properties, psychophysical studies have examined learning of
      visuomotor transformations of either rotation or gain and their generalization.
      However, the neuronal substrates of such complex learning are only beginning to
      be addressed. As an initial step in ensuring the validity of such investigations,
      it must be shown that monkeys indeed learn and generalize visuomotor
      transformations in the same manner as humans. Here, we analyze trajectories and
      velocities of movements as monkeys adapt to either rotational or gain
      transformations. We used rotations with different signs and magnitudes, and gains
      with different signs, and analyzed transfer of learning to untrained movements.
      The results show that monkeys can adapt to both types of transformation with a
      time course that resembles human learning. Analysis of the aftereffects reveals
      that rotation is learned locally and generalizes poorly to untrained directions,
      whereas gain is learned more globally and can be transferred to other amplitudes.
      The results lend additional support to the hypothesis that reaching movements are
      learned locally but can be easily rescaled to other magnitudes by scaling the
      peak velocity. The findings also indicate that reaching movements in monkeys are
      planned and executed very similarly to those in humans. This validates the
      underlying presumption that neuronal recordings in primates can help elucidate
      the mechanisms of motor learning in particular and motor planning in general.

PMID- 15480597
TI  - Predictive control of body mass trajectory in a two-step sequence.
AB  - During a step, the body enters a state of falling as a foot is lifted from the
      ground. This has important implications for the control of body trajectory when
      stepping in different directions. A model has been proposed in which the central
      nervous system controls body trajectory by a predictive, ballistic "throw" of the
      body occurring just before the stepping foot leaves the ground. Here we
      investigate this model and ask how far into the future the body trajectory is
      predetermined by this initial ballistic throw. We measured body centre-of-mass
      (CoM) and foot trajectories during two-step sequences involving stepping onto
      illuminated targets, one for each foot. The targets were varied spatially such
      that leading foot placement could be dissociated from final CoM position. The
      results showed that the body throw was altered when stepping in different
      directions. However, the throw varied only with leading foot placement and not
      with final CoM position. Thus, provided the leading foot was placed identically,
      the same throw was used for steps in which body trajectories would later diverge.
      Furthermore, these trajectories did not diverge while the stepping foot was in
      the air but occurred after it touched down. The results are consistent with the
      ballistic stepping model. However, they suggest that the throw is limited in its
      predictive capacity, being concerned only with where the stepping foot is to be
      placed rather than final CoM position. This constitutes a one-step-at-a-time
      strategy that allows the body to be safely "caught" between steps.

PMID- 15480598
TI  - Knowing your nose better than your thumb: measures of over-grasp reveal that face
      parts are special for grasping.
AB  - Typically, when a grasping response is made, the hand opens wider than the target
      object. We show that this "over-grasp" response is reduced when we reach to parts
      of our own face, relative to when we reach to other body parts or to neutral
      objects. This is not due to reaching to different parts of body space, as over
      grasp responses are indifferent to whether or not other body parts or neutral
      objects are placed close to the face. It is also not due to differences in
      perceptual knowledge of the size of the target object. We conclude instead that
      the familiarity of face parts influences the grasping response directly.
      Subsequent experiments demonstrate that the movement representation determining
      any effect is not based on a torso-centred frame, and not abstracted from the
      specific hand used for grasping. We discuss the implications of the results for
      understanding and measuring motor representations for familiar actions.

PMID- 15480599
TI  - Facilitatory effects of 1 Hz rTMS in motor cortex of patients affected by
      migraine with aura.
AB  - We previously showed paradoxical facilitatory effects of low-frequency repetitive
      transcranial magnetic stimulation (rTMS) on striate and extrastriate cortex of
      patients suffering migraine with aura. In this study we evaluated the effects of
      1 Hz rTMS on the excitability of inhibitory and facilitatory circuits of motor
      cortex to explore whether the abnormal pattern of excitability extends beyond the
      sensory cortex also involving motor areas in migraine with aura. Nine patients
      affected by migraine with aura and eight healthy controls entered into the study.
      The hot spot for activation of the right abductor pollicis brevis (APB) was
      checked by means of a figure-of-eight coil and motor threshold (MT) recorded on
      this point. Nine hundred magnetic stimuli at 1 Hz frequency and 90% MT intensity
      were delivered at the hot spot. Before and after rTMS, intracortical inhibitory
      and facilitatory circuit excitability was assessed by means of a paired pulse
      paradigm (conditioning stimulus 80% MT and test stimulus 120% MT) with two
      different interstimulus intervals: 2 ms (inhibitory) and 10 ms (facilitatory).
      Amplitude of the responses was expressed as the percentage of motor evoked
      potential (MEP) to test stimulus alone. Results showed that in basal condition
      migraineurs present significantly reduced levels of intracortical inhibition
      (ICI) compared to controls. More importantly, opposite results were obtained in
      migraineurs with respect to controls when 1 Hz rTMS was applied. Specifically,
      whereas intracortical facilitation (ICF) significantly decreased in controls, it
      significantly increased in migraineurs. ICI levels were not significantly
      affected by low-frequency stimulation. Our results showed that motor as well as
      sensory cortex of migraine patients present an abnormal modulation of cortical
      excitability, where a relevant role is likely played by the inefficiency of
      inhibitory circuits.

PMID- 15480600
TI  - Blink effects on ongoing smooth pursuit eye movements in humans.
AB  - Blinks are known to affect eye movements, e.g., saccades, slow and fast vergence,
      and saccade-vergence interaction, in two ways: by superimposition of blink
      associated eye movements and changes of the central premotor activity in the
      brainstem. The goal of this study was to determine, for the first time, the
      effects of trigeminal evoked blinks on ongoing smooth pursuit eye movements which
      could be related to visual sensory or premotor neuronal changes. This was
      compared to the effect of a target disappearing for 100-300 ms duration during
      ongoing smooth pursuit (blank paradigm) in order to control for the visual
      sensory effects of a blink. Eye and blink movements were recorded in eight
      healthy subjects with the scleral search coil technique. Blink-associated eye
      movements during the first 50% of the blink duration were non-linearly
      superimposed on the smooth pursuit eye movements. Immediately after the blink
      associated eye movements, the pursuit velocity slowly decreased by an average of
      3.2+/-2.1 degrees /s. This decrease was not dependent on the stimulus direction.
      The pursuit velocity decrease caused by blinks which occluded the pupil more than
      50% could be explained mostly by blanking the visual target. However, small
      blinks that did not occlude the pupil (<10% of lid closure) also decreased smooth
      pursuit velocity. Thus, this blink effect on pursuit velocity cannot be explained
      by blink-associated eye movements or by the blink having blanked the visual
      input. We propose that part of this effect might either be caused by incomplete
      visual suppression during blinks and/or a change in the activity of omnipause
      neurons.

PMID- 15480601
TI  - Modulation of excitatory and inhibitory circuits for visual awareness in the
      human right parietal cortex.
AB  - The balance of specific patterns of excitation and inhibition in critical regions
      of both hemispheres could be relevant in orienting attention over the
      extrapersonal space. In the present study a group of normal subjects had to
      detect small rectangular stimuli presented briefly on a computer screen in three
      different conditions: unilateral presentation either to left or right visual
      periphery or bilateral simultaneous presentation. Paired transcranial magnetic
      stimulation (TMS), was applied over the right parietal cortex 150 ms after the
      presentation of the visual stimuli with different inter-stimulus intervals (ISIs:
      1, 3,5 and 10 ms). When paired TMS was applied 150 ms, but not 100 ms, after
      simultaneous visual presentation, the number of failures in detecting left
      targets increased compared to the single-pulse condition if the ISI was 3 ms; on
      the contrary, it decreased if the ISI was 5 ms. No effects were seen when paired
      pulses of the same intensity were delivered. These findings provide evidence of a
      supramodal-specific pattern of excitability of the right posterior parietal
      cortex in processing visuospatial information.

PMID- 15480602
TI  - "Dark" (compacted) neurons may not die through the necrotic pathway.
AB  - "Dark" neurons were produced in the cortex of the rat brain by hypoglycemic
      convulsions. In the somatodendritic domain of each affected neuron, the
      ultrastructural elements, except for disturbed mitochondria, were remarkably
      preserved during the acute stage, but the distances between them were reduced
      dramatically (ultrastructural compaction). Following a 1-min convulsion period,
      only a few neurons were involved and their environment appeared undamaged. In
      contrast, 1-h convulsions affected many neurons and caused swelling of astrocytic
      processes and neuronal dendrites (excitotoxic neuropil). A proportion of "dark"
      neurons recovered the normal structure in 2 days. The non-recovering "dark"
      neurons were removed from the brain cortex through two entirely different
      pathways. In the case of 1-h convulsions, their organelles swelled, then
      disintegrated and finally dispersed into the neuropil through large gaps in the
      plasma membrane (necrotic-like removal). Following a 1-min convulsion period, the
      non-recovering "dark" neurons fell apart into membrane-bound fragments that
      retained the compacted interior even after being engulfed by astrocytes or
      microglial cells (apoptotic-like removal). Consequently, in contrast to what is
      generally accepted, the "dark" neurons produced by 1-min hypoglycemic convulsions
      do not die as a consequence of necrosis. As regards the case of 1-h convulsions,
      it is assumed that a necrotic-like removal process is imposed, by an excitotoxic
      environment, on "dark" neurons that previously died through a non-necrotic
      pathway. Apoptotic neurons were produced in the hippocampal dentate gyrus by
      intraventricularly administered colchicine. After the biochemical processes had
      been completed and the chromatin condensation in the nucleus had reached an
      advanced phase, the ultrastructural elements in the somatodendritic cytoplasm of
      the affected cells became compacted. If present in an apparently undamaged
      environment such apoptotic neurons were removed from the dentate gyrus through
      the apoptotic sequence of morphological changes, whereas those present in an
      impaired environment were removed through a necrotic-like sequence of
      morphological changes. This suggests that the removal pathway may depend on the
      environment and not on the death pathway, as also assumed in the case of the
      "dark" neurons produced by hypoglycemic convulsions.

PMID- 15480603
TI  - Cardiovascular effects of agmatine within the rostral ventrolateral medulla are
      similar to those of clonidine in anesthetized rats.
AB  - Agmatine was isolated from bovine brain in 1994. It exhibits various functions,
      as a consequence of which it meets the criteria for an endogenous brain
      neurotransmitter. However, its physiological action on the cardiovascular system
      remains unclear. This study was designed to clarify its cardiovascular effects
      when administered into the rostral ventrolateral medulla (RVLM) in anesthetized
      and paralyzed rats. Unilateral injection of clonidine (5 nmol) into the RVLM
      significantly decreased mean arterial pressure (MAP) and heart rate (HR).
      Unilateral injection of agmatine (5 nmol) produced similar effects to clonidine.
      The amplitude of the decrease in HR was the same as with clonidine, but the
      amplitude of the decrease in MAP was less pronounced. The cardiovascular
      inhibition induced by clonidine (5 nmol) and agmatine was abolished by idazoxan
      (5 nmol). Similar to clonidine, agmatine inhibited the pressor effect of L
      glutamate (2 nmol) injected into the RVLM. The duration of this effect (about 6
      min) was shorter than that observed with clonidine (about 12 min). Bilateral
      injection of agmatine into the RVLM inhibited the depressor response induced by
      baroreflex activation (electrical stimulation of the aortic nerve), and this
      effect was similar to, but less pronounced than, that induced by clonidine.
      Idazoxan (5 nmol) antagonized the cardiovascular effects of clonidine and
      agmatine within the RVLM. However, it produced a similar effect to clonidine
      injected into the RVLM. It is concluded that agmatine exerts a similar
      cardiovascular effect to clonidine, with less potency within the RVLM. Idazoxan
      might be a partial agonist for imidazoline I(1) receptors.

PMID- 15480604
TI  - Nonlinear postural control in response to visual translation.
AB  - Recent models of human postural control have focused on the nonlinear properties
      inherent to fusing sensory information from multiple modalities. In general,
      these models are underconstrained, requiring additional experimental data to
      clarify the properties of such nonlinearities. Here we report an experiment
      suggesting that new or multiple mechanisms may be needed to capture the
      integration of vision into the postural control scheme. Subjects were presented
      with visual displays whose motion consisted of two components: a constant
      amplitude, 0.2 Hz oscillation, and constant-velocity translation from left to
      right at velocities between 0 cm/s and 4 cm/s. Postural sway variability
      increased systematically with translation velocity, but remained below that
      observed in the eyes-closed condition, indicating that the postural control
      system is able to use visual information to stabilize sway even at translation
      velocities as high as 4 cm/s. Gain initially increased as translation velocity
      increased from 0 cm/s to 1 cm/s and then decreased. The changes in gain and
      variability provided a clear indication of nonlinearity in the postural response
      across conditions, which were interpreted in terms of sensory reweighting. The
      fact that gain did not decrease at low translation velocities suggests that the
      postural control system is able to decompose relative visual motion into
      environmental motion and self-motion. The eventual decrease in gain suggests that
      nonlinearities in sensory noise levels (state-dependent noise) may also
      contribute to the sensory reweighting involved in postural control. These results
      provide important constraints and suggest that multiple mechanisms may be
      required to model the nonlinearities involved in sensory fusion for upright
      stance control.

PMID- 15480605
TI  - One-hertz subthreshold rTMS increases the threshold for evoking inhibition in the
      human motor cortex.
AB  - Despite indisputable evidence that repetitive transcranial magnetic stimulation
      (rTMS) modulates motor cortical excitability, the effects of subthreshold low
      frequency rTMS on intracortical inhibition (ICI) are controversial. In this paper
      we investigated whether increasing the level of baseline ICI increases the
      sensitivity of ICI for disclosing the after-effects of rTMS on cortical
      excitability. In experiment 1, we studied changes in ICI, tested at two different
      baseline levels, after a train of 900 subthreshold rTMS pulses delivered at 1 Hz.
      In experiment 2, we studied whether the same conditioning rTMS train changed the
      ICI threshold, and in experiment 3 whether it changed the facilitatory I-wave
      interaction. Conditioning rTMS reduced ICI tested at a baseline level of 75% but
      left ICI tested at a baseline level of 50% unchanged. It also increased the ICI
      threshold but left the facilitatory I-wave interaction unchanged. These findings
      suggest that conditioning rTMS selectively reduced ICI tested at a baseline level
      of 75% by increasing the threshold for evoking inhibition in the motor cortex.
      The inhibitory system mediating ICI may therefore be more efficient than other
      motor cortical systems in reducing high cortical excitability after external
      intervention. Hence studies investigating the after-effects of rTMS should
      standardize ICI levels at baseline.

PMID- 15480606
TI  - Individual differences discriminate event-related potentials but not performance
      during response inhibition.
AB  - Event-related brain potentials (ERPs) were recorded from 20 normal participants
      while they completed a Go/NoGo response inhibition task. Previous ERP studies
      have implicated the N2 and P3 waveforms as the main indices of processing in this
      task, and functional brain imaging has shown parietal, prefrontal and anterior
      cingulate cortices to be involved in response inhibition. 32-channel ERP analysis
      revealed amplitude differences in the N2/P3 components when stimuli that required
      a button-press (Go stimuli) were compared with stimuli for which the response had
      to be withheld (No-Go stimuli), and in N2 and P3 latencies when successful
      withholds to No-Go stimuli were compared with unsuccessful attempts to inhibit.
      Further differences in the N2/P3 complex emerged when participants were grouped
      in terms of a measure of absentmindedness (the Cognitive Failures Questionnaire,
      CFQ); larger and earlier components were found for high CFQ respondents. We
      conclude that the latencies of the N2 and P3 may be the critical indicators of
      active inhibitory processes for this task, suggesting that a pattern of
      sequential activation rather than altered activity level in key structures may
      mediate success on the task. In addition, highly absentminded participants
      exhibited larger components for errors than did less absentminded participants
      when performing at the same level, which implies that the absentminded may
      require greater activity in the neural substrates of response inhibition in order
      to accomplish this task at a comparable level of performance to less absentminded
      participants.

PMID- 15480607
TI  - Painful and non-painful pressure sensations from human skeletal muscle.
AB  - Painful and non-painful pressure sensations from muscle are generally accepted to
      exist but the peripheral neural correlate has not been clarified. The aim of the
      present human study was to assess the non-painful and painful pressure
      sensitivity with (1) anaesthetised skin, and (2) anaesthetised skin combined with
      a block of large diameter muscle afferents. The skin was anaesthetised by a
      topically applied anaesthetic cream and later lidocaine was administrated
      subcutaneously. The pressure sensitivity was assessed quantitatively by computer
      controlled pressure stimulation on the anterior tibial muscle. Thresholds to
      detection, pain and pain tolerance were assessed. In the first experiment,
      computer-controlled needle insertion depths evoking touch and pain sensations
      were used to assess the efficacy of cutaneous anaesthesia. Touch and pain
      sensations evoked during needle insertions were found to be superficial in intact
      skin but when anaesthetised, touch sensation was occasionally evoked at depths
      related to penetration of the fascia. With the skin completely anaesthetised to
      brush and von Frey hair pinprick stimulation, skin indentation with the strongest
      von Frey hair caused a sensation described as a deep touch sensation.
      Simultaneously, pressure detection and pain thresholds increased but it was still
      possible to elicit non-painful and painful pressure sensation in all subjects. In
      a second experiment, a differential nerve block of group I and II afferent fibres
      was obtained by full-leg ischaemia simultaneously with cutaneous anaesthesia. The
      efficacy of the tourniquet block was continuously assessed by a battery of
      somatosensory tests (heat, brush, vibration, electrical and movement detection)
      applied at the foot simultaneously with pressure stimulation on the anterior
      tibial muscle. After 20 min of ischaemia, group II afferent fibres mediating the
      sensations of movement detection, vibration and brush on the foot was blocked but
      the heat pain threshold was not affected. In this condition (anaesthetised skin
      and block of group I and II fibres from deep tissue) a pressure sensation was
      evoked in 70% of subjects although the pressure detection threshold was
      increased. The pressure pain sensitivity was decreased, which, however, might
      indicate a partial block of group III and IV muscle afferents. In a third
      experiment, the tactile sensations elicited by electrical stimulation of the
      tibialis anterior muscle and skin at the lower leg were significantly decreased
      after 20 min of ischaemia, validating the blocking effects of group I and II
      nerve fibres. The present data show a marginal contribution of cutaneous
      afferents to the pressure pain sensation that, however, is relatively more
      dependent on contributions from deep tissue group III and IV afferents. Moreover,
      a pressure sensation can be elicited from deep tissue probably mediated by group
      III and IV afferents involving low-threshold mechanoreceptors.

PMID- 15480608
TI  - Can prepared responses be stored subcortically?
AB  - Quick voluntary responses to environmental stimuli are required of people on a
      daily basis. These movements have long been thought to be controlled via cortical
      loops involving processing of the stimulus and generation of a suitable response.
      Recent experiments have shown that in simple reaction time (RT) tasks, the
      appropriate response can be elicited much earlier (facilitated) when the "go"
      signal is replaced by a startling (124 dB) auditory stimulus. In the present
      experiment we combined a startling acoustic stimulus with an established RT
      paradigm that involved simple and choice RT. In a simple RT condition the
      prepared voluntary response was elicited at very short latencies following the
      startle. However, when cortical processing was required prior to responding
      (choice RT task), the startle did not facilitate the voluntary response, and gave
      rise to more movement production errors. Since movements requiring ongoing
      cortical processing following the stimulus are not facilitated by startle, it is
      unlikely that the startle facilitation is due to increased neural activation. In
      contrast, it appears more likely that the startle acts as an early trigger for
      subcortically stored prepared movements since movements that are prepared in
      advance can be initiated at such short latencies (<60 ms).

PMID- 15480609
TI  - Drug prescription in pregnancy: analysis of a large statutory sickness fund
      population.
AB  - OBJECTIVE: To examine the prescription of drugs in Germany prior to, during and
      after pregnancy. METHODS: For the first time, prescription data of a large cohort
      of pregnant women, from a German statutory sickness fund, were available for
      scientific analysis. For each woman who gave birth between June 2000 and May 2001
      reimbursed prescriptions for two periods (90 days each) before pregnancy, three
      during and two after delivery were considered. The drugs were classified
      according to the ATC code. RESULTS: Of the 41,293 women, 96.4% received at least
      one drug during pregnancy. A median of 7 drugs per women was prescribed.
      Excluding vitamins, minerals, iodide and iron, 85.2% received at least one drug
      and the median was 3. Magnesium, which was seldom prescribed outside of
      pregnancy, was by far the most frequently prescribed substance (20% of all
      prescriptions, 61% of the women). Iron (54% of the women) and iodide (31%) were
      also prescribed often. The prescription rates of gynaecological antiinfectives
      (maximum in third trimester: 23% of the women), antacids (max. in third trim.:
      11%), as well as antiemetics and antinauseants (max. in first trim.: 8%) during
      pregnancy considerably increased. A decrease was seen for analgesics,
      antiinflammatory and antirheumatic drugs, muscle relaxants, ophtalmologicals and
      anti-acne preparations, for example. Potential teratogenic drugs were prescribed
      to 1.3% of the women. CONCLUSION: This analysis of a large nation-wide cohort of
      pregnant women showed that during pregnancy drugs were prescribed to most women,
      even when vitamins, minerals, iodide and iron were omitted. Magnesium and iron
      seemed to have been over-prescribed. On the other hand, the official
      recommendation for iodide substitution, to prevent thyroid diseases in mother and
      child, was insufficiently implemented. In our opinion, regular analysis of
      prescription data can identify potential harmful therapies and focal points where
      guidelines are needed and can check their implementation.

PMID- 15480610
TI  - Multifocal metachronous giant cell tumor in a 15-year-old boy.
AB  - We report a case of multifocal metachronous giant cell tumor (GCT) that involved
      the fibula, tibia, and sacrum of a 15-year-old boy. Multifocal GCT of bone
      presenting in children is an exceedingly rare phenomenon; however, there is
      evidence that multifocal GCT presents, on average, at a younger age than solitary
      GCT. Pediatric radiologists should be aware of this when encountering a single
      lesion with characteristic radiographic features of GCT and when encountering
      multiple lytic skeletal lesions.

PMID- 15480611
TI  - Morning glory disc anomaly, midline cranial defects and abnormal carotid
      circulation: an association worth looking for.
AB  - We report on a 4-year-old boy who presented to the ophthalmology department for
      assessment of convergent strabismus. Ophthalmic examination showed a left morning
      glory optic disc anomaly and retinal detachment. Plain films obtained for
      investigation of short stature prior to ophthalmic examination revealed delayed
      bone age. Ophthalmological findings prompted CT and MRI imaging and angiographic
      investigations. Midline cranial defects and abnormal carotid circulation were
      identified. These findings may be associated with morning glory optic disc
      anomaly, and their association is often under-recognized. It is important that
      clinicians and radiologists be aware of this spectrum of disorders, as the
      vascular abnormalities may predispose the patient to transient ischemic attacks
      and strokes. Growth delay may result from hypopituitarism.

PMID- 15480612
TI  - Ultrasonographic assessment of the gallbladder in 21 children with portal vein
      thrombosis.
AB  - BACKGROUND: Portal vein thrombosis (PVT) is one of the most frequent causes of
      portal hypertension (PH) during childhood. Portal systemic collateral vessels
      occur at several locations, including the gallbladder (GB). OBJECTIVE: To
      evaluate the GB in patients with PVT using US to assess GB wall thickness and its
      function, and the incidence of lithiasis and varices. MATERIALS AND METHODS: A
      prospective study was done on 21 children and young adults whose ages ranged from
      17 months to 20 years and 10 months (mean age: 11 years and 7 months). A control
      group was matched for age and sex. All of the patients and controls fasted for at
      least 6 h prior to the US examination. The GB measurements included anterior wall
      thickness. These measurements were obtained before the ingestion and then 30 and
      60 min after the ingestion of a meal containing at least 25 g of fat. The rate of
      GB contractility was calculated based on these results. The presence of varices
      in the GB wall was detected by the characteristic serpentine shape of the
      intramural vessels and by the venous flow using pulse duplex and color Doppler
      imaging. The presence of biliary lithiasis was confirmed by shadowing. The chi
      square test, the exact Fisher test and the Mann-Whitney test were used to compare
      the results. RESULTS: Biliary lithiasis occurred in 3 (14.2%) of the 21 patients.
      The GB wall was thickened in 13 (61.9%) of the 21 patients, which corresponded
      with the number of patients with GB varices. The wall dimensions of all the
      controls were within normal limits. In patients with PVT; GB contractility was
      lower than in the 21 patients used as control and resulted in a significant
      difference in all of the measurements. CONCLUSION: GB varices are very common in
      children with PVT, and it is noted especially in patients whose GB wall was
      thickened and in whom the GB contractility was reduced. Lithiasis could be a
      consequence of the decreased contractility of GB.

PMID- 15480613
TI  - Single-session percutaneous ethanol sclerotherapy in simple renal cysts in
      children: long-term follow-up.
AB  - BACKGROUND: Simple renal cysts are rare in children and managed conservatively
      unless symptomatic. OBJECTIVE: To demonstrate the efficacy and long-term results
      of single-session ethanol sclerotherapy in symptomatic simple renal cysts in
      children. MATERIALS AND METHODS: Three simple renal cysts in three children (age
      1, 5 and 16 years) were included in the study. Indications for treatment were
      flank pain (n = 1), hypertension (n = 1), and increasing cyst size and urinary
      tract infection (n = 1). The mean follow-up period was 5.5 years (range 3-7
      years). The procedures were performed with the guidance of US and fluoroscopy and
      under IV sedation. After the cystogram, 95% ethanol with a volume of 40% of the
      cyst volume (but not more than 100 ml) was used as the sclerosing agent. RESULTS:
      Two cysts disappeared completely, while the volume reduction was 99% for the
      third cyst at the end of the first year. CT demonstrated calcification of the
      cyst without an enhancing soft-tissue component in the third one 7 years after
      sclerotherapy. After the procedures, hypertension and pain resolved without any
      medication. There were no complications during the procedures or during follow
      up. Cytological examination was unremarkable in all patients. CONCLUSIONS:
      Percutaneous treatment of symptomatic simple renal cysts in children with single
      session ethanol sclerotherapy is a safe, effective and minimally invasive
      procedure. Calcification owing to sclerotherapy can be observed on follow-up.

PMID- 15480614
TI  - Solid (stromal predominance) hepatic mesenchymal hamartoma.

PMID- 15480615
TI  - Early diagnosis of cerebral involvement in Sturge-Weber syndrome using high
      resolution BOLD MR venography.
AB  - Sturge-Weber syndrome (SWS) is a congenital disorder characterized by a vascular
      birthmark and neurological abnormalities. Typical imaging findings using MRI or
      CT are superficial cerebral calcification, atrophy and leptomeningeal
      enhancement. We present a neonate diagnosed with SWS because of a port-wine
      stain. In the absence of neurological symptoms the first MRI was performed when
      he was 4 months old, and follow-up MRI studies were performed after his first
      seizure at the age of 12 months. MRI was performed using standard sequences
      before and after administration of IV gadolinium. A high-resolution T2*-weighted,
      rf-spoiled 3D gradient-echo sequence with first-order flow compensation in all
      three directions was used for additional venographic imaging [blood-oxygen-level
      dependent (BOLD) venography]. The initial conventional MRI sequences did not
      demonstrate any abnormality, but BOLD venography identified leptomeningeal
      internal veins. Follow-up MRI after the first onset of seizures demonstrated
      strong leptomeningeal enhancement, while BOLD venography revealed pathological
      medullary and subependymal veins as well as deep venous structures. At this time
      there were the first signs of atrophy and CT showed marginal calcifications. This
      report demonstrates that high-resolution BOLD MR venography allows early
      diagnosis of venous anomalies in SWS, making early therapeutic intervention
      possible.

PMID- 15480616
TI  - Infantile Refsum disease: serial evaluation with MRI.
AB  - Refsum disease is a rare metabolic disorder, which is characterized by the
      accumulation of phytanic acid in the blood and tissues, including the brain. A
      variant of this condition that occurs in young children is called infantile
      Refsum disease. The MRI findings of symmetrical signal change involving the
      corticospinal tracts, cerebellar dentate nuclei, and corpus callosum are
      characteristic. We report the serial MRI findings of a child with this rare
      metabolic disorder.

PMID- 15480618
TI  - Sonographic evaluation of oesophageal atresia and tracheo-oesophageal fistula.
AB  - BACKGROUND: Oesophageal atresia and tracheo-oesophageal fistula (TOF) in neonates
      and young infants is routinely diagnosed using frontal and lateral chest
      radiographs in the former and fluoroscopic studies in the latter. OBJECTIVE: The
      aim of the study was to assess whether a combination of mediastinal and abdominal
      sonography can be used for the diagnosis of these anomalies in paediatric
      patients. MATERIAL AND METHODS: Sonography was performed in 16 neonates (age
      range 1-20 days; mean 4 days) with radiologically confirmed oesophageal atresia
      or isolated TOF. A small volume of saline solution was instilled into the blind
      upper oesophageal pouch to document its extension. RESULTS: Sonography identified
      11 neonates with the most common type of oesophageal atresia (type IIIb), one
      patient with type II and one with type IIIa anomaly. The length of the upper
      pouch and the features of its wall were clearly documented in all cases. In one
      case, two upper TOF were first diagnosed by mediastinal sonography and later
      confirmed by fluoroscopy. In two of three cases with isolated TOF, the fistula
      could be located sonographically by detecting moving air bubbles. In all cases
      the position of the aortic arch, as well as associated malformations, could be
      documented during a single US examination. CONCLUSIONS: These results indicate
      that mediastinal sonography is a useful tool for the diagnosis of oesophageal
      atresia and, if air bubbles can be detected, isolated TOF.

PMID- 15480617
TI  - Congenital cystic adenomatoid malformation: is there a difference between the
      antenatally and postnatally diagnosed cases?
AB  - BACKGROUND: The majority of congenital cystic adenomatoid malformation (CCAM)
      lesions are diagnosed antenatally. A few cases however may not be recognised
      antenatally and present in infancy or later childhood with chest symptoms,
      including chest infection. OBJECTIVE: To review the clinical and radiological
      spectrum of CCAM, comparing the antenatally with the postnatally diagnosed cases.
      MATERIALS AND METHODS: Fifteen cases of antenatally and/or postnatally diagnosed
      and histopathologically proven CCAM were retrospectively identified over a period
      of 4 years. Clinical notes, chest radiograph and chest CT were reviewed in all
      cases. RESULTS: Nine patients were diagnosed antenatally and six postnatally. All
      antenatally diagnosed patients were asymptomatic at birth, six remained
      asymptomatic until they had elective surgery and the remaining three developed
      symptoms before the age of 2 years. In the postnatally diagnosed group, one
      patient was symptomatic at birth and one patient presented at 16 years; the
      remaining four presented before the age of 2 years. Depending on the type of
      lesion, we recognised five radiographic patterns of CCAM. CCAM lesions were
      classified as CT Stocker type I in seven cases, type II in seven cases and type
      III in one case. CONCLUSIONS: No significant difference was found between the two
      groups. Recognition of these lesions antenatally would benefit patients by
      avoiding delay in making the diagnosis, which can lead to serious complications.
      CT was successful in accurately diagnosing and grading CCAM lesions.

PMID- 15480619
TI  - Liver volume in thalassaemia major: relationship with body weight, serum
      ferritin, and liver function.
AB  - BACKGROUND: It is not known whether body weight alone can adjust for the volume
      of liver in the calculation of the chelating dose in beta-thalassaemia major
      patients, who frequently have iron overload and hepatitis. OBJECTIVE: The
      hypothesis is that liver volume in children and adolescents suffering from beta
      thalassaemia major is affected by ferritin level and liver function. MATERIALS
      AND METHODS: Thirty-five beta-thalassaemia major patients aged 7-18 years and 35
      age- and sex-matched controls had liver volume measured by MRI. Serum alanine
      aminotransferase (ALT) and ferritin levels were obtained in the thalassaemia
      major patients. RESULTS: Body weight explained 65 and 86% of the change in liver
      volume in beta-thalassaemia major patients and age-matched control subjects,
      respectively. Liver volume/kilogram body weight was significantly higher (P <
      0.001) in thalassaemia major patients than in control subjects. There was a
      significant correlation between ALT level and liver volume/kilogram body weight
      (r = 0.55, P = 0.001). Patients with elevated ALT had significantly higher liver
      volume/kilogram body weight (mean 42.9 +/- 12 cm3/kg) than control subjects (mean
      23.4 +/- 3.6 cm3/kg) and patients with normal ALT levels (mean 27.4 +/- 3.6
      cm3/kg). CONCLUSIONS: Body weight is the most important single factor for liver
      volume changes in thalassaemia major patients, but elevated ALT also has a
      significant role. Direct liver volume measurement for chelation dose adjustment
      may be advantageous in patients with elevated ALT.

PMID- 15480620
TI  - Pseudoaneurysm in children: diagnosis and interventional management.
AB  - Pseudoaneurysms (PAn) are uncommon in adults and even less common in children.
      They are most often encountered after iatrogenic arterial injury. Presentation
      may be substantially delayed after the iatrogenic event, and diagnosis can be
      difficult, especially when the PAn occurs in an unexpected location. Treatment of
      PAn has evolved during the last two decades from a reliance on surgical resection
      to US-guided compression, coil embolization, covered stents, and stent-graft
      exclusion. More recently, direct percutaneous US-guided thrombin injection has
      been used in the treatment of PAn. We present three cases of successful PAn
      thrombosis by US-guided percutaneous thrombin injection in children, one of the
      epigastric artery and two of the femoral artery.

PMID- 15480622
TI  - Soft perforation of planar bilayer lipid membranes of
      dipalmitoylphosphatidylcholine at the temperature of the phase transition from
      the liquid crystalline to the gel state.
AB  - In contrast to the widely used method of electroporation, the method of soft
      perforation of lipid bilayers is proposed. It is based on the structural
      rearrangement of the lipid bilayer formed from disaturated phospholipids at the
      temperature of the phase transition from the liquid crystalline state to the gel
      state. This allows us to obtain a lipid pore population without the use of a
      strong electric field. It is shown that the planar lipid bilayer membrane (pBLM)
      formed from dipalmitoylphosphatidylcholine in 1 M LiCl aqueous solution exhibits
      the appearance of up to 50 lipid pores per 1 mm(2) of membrane surface, with an
      average single pore conductivity of 31 +/- 13 nS. The estimation of a single pore
      radius carried out with water-soluble poly(ethylene glycol)s (PEGs) showed that
      the average pore radius ranged between 1.0-1.7 nm. It was found experimentally
      that PEG-1450, PEG-2000, and PEG-3350 should be in a position to block the single
      pore conductivity completely, while PEG-6000 fully restored the ionic
      conductivity. The similarity of these PEG effects to ionic conductivity in
      protein pores makes it possible to suggest that the partition of the PEG
      molecules between the pore and the bulk solution does not depend on the nature of
      the chemical groups located in the pore wall.

PMID- 15480621
TI  - Interrelation between HeLa-S3 cell transfection and hemolysis in red blood cell
      suspension using pulsed ultrasound of various duty cycles.
AB  - We have studied the in vitro transfection of a plasmid DNA with the lacZ gene to
      HeLa-S3 cells and hemolysis in a red blood cell (RBC) suspension under pulsed
      ultrasound with duty cycles gamma of 10, 20 and 30% using a digital sonifier at a
      frequency of 20 kHz and an intensity of 6.2 W/cm(2) on the surface of a horn tip.
      Cultured HeLa-S3 cells in suspension were exposed to pulsed ultrasound for an
      apparent exposure time t' from 0 to 60 s. HeLa-S3 viability decreased as a single
      exponential function of the total exposure time t = gammat' with a common time
      constant tau = 3.8 s for three duty cycles. Transfection was evaluated by
      counting the number of beta-galactosidase(beta-Gal)-positive cells relative to
      the total number of cells. Pulsed ultrasound provided an enhanced transfer of the
      beta-Gal plasmid to HeLa-S3 cells, 3.4-fold as compared with that in the case of
      the control. The optimal transfection efficiencies were 0.75, 0.80 and 0.74% near
      t = tau with gamma = 10, 20 and 30%, respectively. The number ratio of beta-Gal
      positive cells to the surviving cells after exposure increased with t' according
      to a modified logistic equation. The degree of hemolysis also increased
      exponentially with t' at a time constant tau' = tau(0)/gamma for the RBC
      suspension in physiological saline at a hematocrit concentration of 0.5% with
      tau(0) = 0.9 s. Thus the total exposure time for the optimal transfection
      efficiency was tau, that is, nearly four times of tau(0). Hemolysis in the RBC
      suspension may be a useful model for determining optimal transfection by pulsed
      ultrasound of various duty cycles.

PMID- 15480623
TI  - Recombinant expression systems in the pharmaceutical industry.
AB  - In terms of downstream processing efficiency, secretory expression systems offer
      potential advantages for the production of recombinant proteins, compared with
      inclusion body forming cytosolic systems. However, for high-volume therapeutics
      like insulin, the product yields of the majority of the potentially available
      secretory systems is not yet fully competitive. Current strategies to improve
      productivity and secretion efficiency comprise: (1) enhancement of gene
      expression rates, (2) optimization of secretion signal sequences, (3)
      coexpression of chaperones and foldases, (4) creation of protease deficient
      mutants to avoid premature product degradation and (5) subsequent breeding and
      mutagenesis. For the production of non-glycosylated proteins and proteins, which
      are natively glycosylated but are also pharmacologically active without
      glycosylation, prokaryotes, which usually lack metabolic pathways for
      glycosylation, are theoretically the most suitable organisms and offer two
      alternatives: either Escherichia coli strains are conditioned to be efficient
      secreters or efficient native secreters like Bacillus species are accordingly
      developed. To fully exploit the secretory capacity of fungal species, a deeper
      understanding of their posttranslational modification physiology will be
      necessary to steer the degree and pattern of glycosylation, which influences both
      folding and secretion efficiency. Insect and mammalian cells display
      posttranslational modification patterns very similar or identical to humans, but
      in view of the entailed expenditures, their employment can only be justified if
      their modification machinery is required to ensure a desired pharmacological
      activity.

PMID- 15480624
TI  - Microbial population dynamics during fed-batch operation of commercially
      available garbage composters.
AB  - Microbial populations in terms of quantity, quality, and activity were monitored
      during 2 months of start-up operation of commercially available composters for
      fed-batch treatment of household biowaste. All the reactors, operated at a waste
      loading rate of 0.7 kg day(-1) (wet wt), showed a mass reduction efficiency of 88
      93%. The core temperature in the reactors fluctuated between 31 degrees C and 58
      degrees C due to self-heating. The pH declined during the early stage of
      operation and steadied at pH 7.4-9.3 during the fully acclimated stage. The
      moisture content was 48-63% early in the process and 30-40% at the steady state.
      Both direct total counts and plate counts of bacteria increased via two phases
      (designated phases I, II) and reached an order of magnitude of 10(11) cells g(-1)
      (dry wt) at the steady state. Microbial community changes during the start-up
      period were studied by culture-independent quinone profiling and denatured
      gradient gel electrophoresis (DGGE) of PCR-amplified 16S rDNA. In all the
      reactors, ubiquinones predominated during phase I, whereas partially saturated
      menaquinones became predominant during phase II. This suggested that there was a
      drastic population shift from ubiquinone-containing Proteobacteria to
      Actinobacteria during the start-up period. The DGGE analysis of the bacterial
      community in one of the reactors also demonstrated a drastic population shift
      during phase I and the predominance of members of the phyla Proteobacteria and
      Bacteroidetes during the overall period. But this molecular analysis failed to
      detect actinobacterial clones from the reactor at any stage.

PMID- 15480625
TI  - Glutathione: a review on biotechnological production.
AB  - This Mini-Review summarizes the historic developments and technological
      achievements in the biotechnological production of glutathione in the past 30
      years. Glutathione is the most abundant non-protein thiol compound present in
      living organisms. It is used as a pharmaceutical compound and can be used in food
      additives and the cosmetic industries. Glutathione can be produced using
      enzymatic methods in the presence of ATP and its three precursor amino acids (L
      glutamic acid, L-cysteine, glycine). Alternatively, glutathione can be produced
      by direct fermentative methods using sugar as a starting material. In the latter
      method, Saccharomyces cerevisiae and Candida utilis are currently used to produce
      glutathione on an industrial scale. At the molecular level, the genes gshA and
      gshB, which encode the enzymes gamma-glutamylcysteine synthetase and glutathione
      synthetase, respectively, have been cloned from Escherichia coli and over
      expressed in E. coli, S. cerevisiae, and Lactococcus lactis. It is anticipated
      that, with the design and/or discovery of novel producers, the biotechnological
      production of glutathione will be further improved to expand the application
      range of this physiologically and medically important tripeptide.

PMID- 15480628
TI  - beta-galactosidase from Bifidobacterium adolescentis DSM20083 prefers beta(1,4)
      galactosides over lactose.
AB  - Abstract A beta-galactosidase gene (beta-Gal II) from Bifidobacterium
      adolescentis DSM 20083 was cloned into a pbluescript SK (-) vector and expressed
      in Escherichia coli. The recombinant enzyme was purified from the cell extract by
      anion-exchange and size-exclusion chromatography. beta-Gal II had a native
      molecular mass of 235 kDa and the subunits had a molecular mass of 81 kDa,
      indicating that beta-Gal II occurs as a trimer. The enzyme was classified as
      belonging to glycosyl hydrolase family 42. The optimal pH was 6.0 and the optimal
      temperature was 50 degrees C, usingp-nitrophenyl-(beta-D-galactopyranoside as a
      substrate. The Km and Vmax for Gal(beta1-4)Gal were 60 mM and 1129 U/mg,
      respectively. The recombinant beta-Gal II was highly active towards Gal(beta1
      4)Gal and Gal (beta1-4)Gal-containing oligosaccharides; only low activity was
      observed towards Gal(beta1-3)Gal, lactose, and Gal (beta1-3)GalOMe. No activity
      was found towards Gal(beta1-6)Gal, Gal(beta -4)Man, Gal(alpha1-4)Gal, Gal(alpha1
      3)Gal(beta1-4)Gal, cellobiose, maltose and sucrose. beta-Gal II was inhibited at
      high substrate concentrations (100 mg/ml) and no transglycosylation activity was
      found. At lower substrate concentrations (10 mg/ml) only low transglycosylation
      activity was found; the Gal/[Gal(beta1-4)]2Gal peak area ratio was 9:1.

PMID- 15480630
TI  - A novel immobilised design for the production of the heterologous protein
      lysozyme by a genetically engineered Aspergillus niger strain.
AB  - A novel immobilisation design for increasing the final concentration of the
      heterologous protein lysozyme by a genetically engineered fungus, Aspergillus
      niger B1, was developed. A central composition design was used to investigate
      different immobilised polymer types (alginate and pectate), polymer concentration
      [24% and 4% (w/v)], inoculum support ratios (1:2 and 1:4) and gel-inducing agent
      concentration [CaCl(2), 2% and 3.5% (w/v)]. Studies of the kinetics of production
      showed that optimum lysozyme productivity occurred after 10 days. Lysozyme
      production was significantly affected by polymer type, polymer concentration, and
      inoculum support ratio. Overall, immobilisation in Ca-pectate resulted in higher
      lysozyme production compared to that in Ca-alginate. Similar effects were
      observed when the polymer concentration was reduced. Regardless of polymer type
      and concentration, increasing the fungal inoculum level increased lysozyme
      production. A significantly higher lysozyme yield was achieved with Ca-pectate in
      comparison to Ca-alginate (approximately 20-23 mg l(-1) and 0.5-2 mg l(-1),
      respectively). The maximum lysozyme yield achieved was about 23 mg l(-1) by
      immobilisation in Ca-pectate 2% (w/v) with 33% (v/v) mycelium and 3.5% (w/v) gel
      inducing agent (CaCl(2)). Response surface methodology was used to investigate
      the effect of pH and water activity (a(w)). The best medium pH was 4.5-5.0, and
      bead a(w) for optimum lysozyme yield was 0.94, regardless of polymer type.

PMID- 15480631
TI  - Development of an improved procedure for isolation and purification of
      exopolysaccharides produced by Lactobacillus delbrueckii subsp. bulgaricus NCFB
      2483.
AB  - A method was developed for the isolation and purification of exopolysaccharide
      (EPS) produced by Lactobacillus delbrueckii subsp. bulgaricus NCFB 2483 that can
      be adapted for industrial-scale operation. Hydrolyzed milk medium, which was
      ultrafiltered to remove molecular species larger than 2.5 x 10(5) Da, was found
      to be a suitable growth medium for the bacteria, which produced approximately 400
      mg EPS/l . Optimal isolation of EPS was achieved using centrifugation, filtration
      and ethanol precipitation methods. Insoluble and soluble EPS fractions were
      obtained. The soluble fraction was purified using a series of ethanol
      precipitations to achieve approximately 98% (w/w) purity. This fraction consisted
      of galactose, glucose, rhamnose and mannose in the ratio of approximately
      5:1:0.6:0.5, with traces of glucosamine.

PMID- 15480633
TI  - Elicitor-induced nitric oxide burst is essential for triggering catharanthine
      synthesis in Catharanthus roseus suspension cells.
AB  - Elicitor prepared from the cell walls of Penicillium citrinum induced multiple
      responses in Catharanthus roseus suspension cells, including rapid generation of
      nitric oxide (NO), sequentially followed by enhancement of catharanthine
      production by C. roseus cells. Elicitor-induced catharanthine biosynthesis was
      blocked by NO-specific scavenger 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline
      1-oxyl-3-oxide and nitric oxide synthase (NOS) inhibitor S,S'-1,3-phenylene
      bis(1,2-ethanediyl)-bis-isothiourea (PBITU). PBITU also strongly inhibited
      elicitor-induced NO generation by C. roseus suspension cells. The inhibiting
      effect of PBITU on elicitor-induced catharanthine production was reversed by
      external application of NO via the NO-donor sodium nitroprusside. The results
      strongly suggested that NO, generated by NOS or NOS-like enzymes in C. roseus
      suspension cells when treated with the fungal elicitor, was essential for
      triggering catharanthine synthesis.

PMID- 15480634
TI  - Carbon isotope fractionation during cis-trans isomerization of unsaturated fatty
      acids in Pseudomonas putida.
AB  - The molecular mechanism of the unique cis to trans isomerization of unsaturated
      fatty acids in the solvent-tolerant bacterium Pseudomonas putida S12 was studied.
      For this purpose, the carbon isotope fractionation of the cis-trans isomerase was
      estimated. In resting cell experiments, addition of 3-nitrotoluene for activation
      of the cis-trans isomerase resulted in the conversion of the cis-unsaturated
      fatty acids into the corresponding trans isomers. For the conversion of C16:1 cis
      to its corresponding trans isomer, a significant fractionation was measured. The
      intensity of this fractionation strongly depended on the rate of cis-trans
      isomerization and the added concentration of 3-nitrotoluene, respectively. The
      presence of a significant fractionation provides additional indication for a
      transition from the sp carbon linkage of the cis-double bond to an intermediate
      sp3 within an enzyme-substrate complex. The sp2 linkage is reconstituted after
      rotation to the trans configuration has occurred. As cytochrome c plays a major
      role in the catabolism of Cti polypeptide, these findings favour a mechanism for
      the enzyme in which electrophilic iron (Fe(3+)), provided by a heme domain,
      removes an electron of the cis double bond thereby transferring the sp2 linkage
      into sp3.

PMID- 15480636
TI  - Identification and characterization of a novel D-amidase gene from Variovorax
      paradoxus and its expression in Escherichia coli.
AB  - The gene for the newly described D-amidase from Variovorax paradoxus (Krieg et
      al. 2002) was cloned and functionally expressed in Escherichia coli. Since native
      enzyme was available in minute amounts only, we determined the N-terminal
      sequence of the enzyme and utilized the Universal GenomeWalker Approach to make
      use of the common internal sequence of the amidase signature family. The high GC
      content of the gene made it necessary to employ an appropriate DNA polymerase in
      the amplification reactions. Thus, the sequence of the complete gene and the
      flanking regions was established. In independent experiments, the gene was then
      amplified from genomic DNA of V. paradoxus, expressed in E. coli, and
      characterized. The recombinant enzyme has a specific activity of 1.7 units/mg
      with racemic tert-leucine amide as substrate and is a homodimer of 49.6-kDa
      monomers.

PMID- 15480637
TI  - A new ether bond-splitting enzyme found in Gram-positive polyethylene glycol 6000
      utilizing bacterium, Pseudonocardia sp. strain K1.
AB  - Pseudonocardia sp. strain K1 is the only Gram-positive bacterium among the
      bacteria aerobically metabolizing polyethylene glycol (PEG). Generally, PEG is
      metabolized by an oxidative pathway in which a terminal alcohol group of PEG is
      oxidized to aldehyde and to carboxylic acid and then an ether bond is oxidatively
      cleaved. As the cell-free extract of Pseudonocardia sp. strain K1 has PEG
      dehydrogenase, PEG aldehyde dehydrogenase and diglycolic acid (DGA) dehydrogenase
      (DGADH) activities, all of which are constitutively formed, the strain has a
      metabolic pathway similar to that so far known. We purified an ether bond
      splitting enzyme as DGADH. The molecular mass of the enzyme was estimated to be
      55 kDa; and it consisted of two identical subunits. The enzyme oxidatively
      cleaved both an ether bond of PEG 3000 dicarboxylic acid and DGA. The N-terminal
      amino acid sequence of the purified enzyme had high homology with various
      superoxide dismutases and the enzyme had also superoxide dismutase activity. The
      atomic absorption spectrum showed that approximately one atom of Fe was included
      in each subunit of the enzyme. DGADH activity increased in the cells grown in a
      PEG medium supplemented with FeCl(3). Thus, we concluded that the enzyme purified
      from Pseudonocardia sp. strain K1 is a new ether bond-splitting enzyme.

PMID- 15480638
TI  - Overproduction of recombinant laccase using a homologous expression system in
      Coriolus versicolor.
AB  - One of the major extracellular enzymes of the white-rot fungus Coriolus
      versicolor is laccase, which is involved in the degradation of lignin. We
      constructed a homologous system for the expression of a gene for laccase III
      (cvl3) in C. versicolor, using a chimeric laccase gene driven by the promoter of
      a gene for glyceraldehyde-3-phosphate dehydrogenase (gpd) from this fungus. We
      transformed C. versicolor successfully by introducing both a gene for hygromycin
      B phosphotransferase (hph) and the chimeric laccase gene. In three independent
      experiments, we recovered 47 hygromycin-resistant transformants at a
      transformation frequency of 13 transformants microg(-1) of plasmid DNA. We
      confirmed the introduction of the chimeric laccase gene into the mycelia of
      transformants by a polymerase chain reaction in nine randomly selected
      transformants. Overproduction of extracellular laccase by the transformants was
      revealed by a colorimetric assay for laccase activity. We examined the
      transformant (T2) that had the highest laccase activity and found that its
      activity was significantly higher than that of the wild type, particularly in the
      presence of copper (II). Our transformation system should contribute to the
      efficient production of the extracellular proteins of C. versicolor for the
      accelerated degradation of lignin and aromatic pollutants.

PMID- 15480639
TI  - The impact of technical conditions of X-ray imaging on reproducibility and
      precision of digital computer-assisted X-ray radiogrammetry (DXR).
AB  - OBJECTIVE: To evaluate the reproducibility of imaging and analysis for bone
      mineral density (BMD) determination using digital computer-assisted X-ray
      radiogrammetry (DXR; Pronosco X-posure, version V.2, Sectra Pronosco, Denmark);
      to verify potential factors that influence BMD extrapolation such as tube
      voltage, film-focus distance (FFD), film quality and brand (Kodak T-MAT-Plus,
      Konika SRH, Agfa Scopix), imaging technology (conventional, digital), imaging
      system (Kodak, Agfa) and exposure level (mAs); and to clarify whether DXR
      analysis based on printouts of digital images is comparable to analysis of
      conventional images. DESIGN AND PATIENTS: The hand of a cadaver was X-rayed using
      varied parameters: 4-8 mAs, 40-52 kV, 90-130 cm FFD. Radiographs under
      standardised conditions were performed 10 times using a conventional machine
      (Philips Super 80 CP) and the printouts of a digital system (Digital Diagnost
      Philips Optimus) for the analysis of reproducibility. One image was scanned and
      analysed 10 times additionally for imaging reproducibility. RESULTS: Reliability
      error of the system for the imaging process using conventional radiographs-rays
      was 0.49% (standard conditions: 6 mAs, 40 kV, 1 m FFD), using printouts of
      digital images was 2.89% (4 mAs, 42 kV, 1 m FFD) and regarding the analysis
      process was 0.22%. BMD calculation is not affected by alterations in FFD
      (precision error 1.21%), mAs (0.83%) or film quality/brand (0.38%), but differs
      significantly depending on tube voltage (2.70%). The system was not able to
      analyse conventional images with tube voltages of 49/52 kV. CONCLUSION: DXR
      technology is stable with most of the tested parameters. Normative data should
      exclusively be used for calculations using similar tube voltage or correction
      factors. All other parameters had no significant influence on the BMD
      calculation. Reproducibility is high. For technical reasons it is not recommended
      to use the printouts of digital images for BMD determination.

PMID- 15480640
TI  - Magnetic resonance imaging of the elbow. Part II: Abnormalities of the ligaments,
      tendons, and nerves.
AB  - Part II of this comprehensive review on magnetic resonance imaging of the elbow
      discusses the role of magnetic resonance imaging in evaluating patients with
      abnormalities of the ligaments, tendons, and nerves of the elbow. Magnetic
      resonance imaging can yield high-quality multiplanar images which are useful in
      evaluating the soft tissue structures of the elbow. Magnetic resonance imaging
      can detect tears of the ulnar collateral ligament and lateral collateral ligament
      of the elbow with high sensitivity and specificity. Magnetic resonance imaging
      can determine the extent of tendon pathology in patients with medial
      epicondylitis and lateral epicondylitis. Magnetic resonance imaging can detect
      tears of the biceps tendon and triceps tendon and can distinguishing between
      partial and complete tendon rupture. Magnetic resonance imaging is also helpful
      in evaluating patients with nerve disorders at the elbow.

PMID- 15480641
TI  - Magnetic resonance imaging of the elbow. Part I: normal anatomy, imaging
      technique, and osseous abnormalities.
AB  - Part I of this comprehensive review on magnetic resonance imaging of the elbow
      discusses normal elbow anatomy and the technical factors involved in obtaining
      high-quality magnetic resonance images of the elbow. Part I also discusses the
      role of magnetic resonance imaging in evaluating patients with osseous
      abnormalities of the elbow. With proper patient positioning and imaging
      technique, magnetic resonance imaging can yield high-quality multiplanar images
      which are useful in evaluating the osseous structures of the elbow. Magnetic
      resonance imaging can detect early osteochondritis dissecans of the capitellum
      and can be used to evaluate the size, location, stability, and viability of the
      osteochondritis dissecans fragment. Magnetic resonance imaging can detect early
      stress injury to the proximal ulna in athletes. Magnetic resonance imaging can
      detect radiographically occult fractures of the elbow in both children and
      adults. Magnetic resonance imaging is also useful in children to further evaluate
      elbow fractures which are detected on plain-film radiographs.

PMID- 15480642
TI  - Popliteal vascular entrapment syndrome caused by a rare anomalous slip of the
      lateral head of the gastrocnemius muscle.
AB  - Popliteal vascular entrapment syndrome can result in calf claudication, aneurysm
      formation, distal arterial emboli, or popliteal vessel thrombosis. The most
      commonly reported causes of this syndrome have been anomalies of the medial head
      of the gastrocnemius muscle as it relates to the course of the popliteal artery.
      We report two cases of rare anomalous slips of the lateral head of the
      gastrocnemius muscle causing popliteal vascular entrapment syndrome.

PMID- 15480643
TI  - Extracorporeal shock wave therapy in calcific tendinitis of the shoulder.
AB  - OBJECTIVE: To investigate clinical (pain, mobility) and radiological (resolution
      of calcium deposits) efficacy of different energy levels of extracorporeal shock
      wave therapy (ESWT) in calcific tendinitis of the shoulder. DESIGN AND PATIENTS:
      There were 90 study subjects with radiographically verified calcific tendinitis
      of one shoulder, mean age 52+/-6 years (range 29-65 years; females:males=55:35),
      all of whom had had symptoms for at least 6 months and substantial restriction of
      shoulder mobility and pain that required taking anti-inflammatory drugs. Calcium
      deposits were of type I or type II (clearly circumscribed and dense) and ranged
      from 1 cm to 3 cm in diameter. Subjects were divided into three groups to receive
      ESWT at one of two energy levels (E1=0.15 mJ/mm2, E2=0.44 mJ/mm2) or sham
      treatment. Treatment was given at 6 weekly intervals until symptoms resolved,
      five treatments had been given or the subject dropped out of the programme.
      RESULTS: All subjects in groups E1 and E2 completed the programme. Those in group
      E1 had significantly less pain during treatment but more treatments than those in
      group E2, and at 6 month follow-up had residual calcification and recurrence of
      pain (87%). Subjects in group E2 had no residual calcification or recurrence of
      pain. Sham treatment had no effect. There were no side effects except a small
      number of haematomas (2 in E1, 6 in E2; maximum size 2 cm). CONCLUSION: ESWT in
      calcific tendinitis of the shoulder is very effective. It does not have
      significant side effects at an energy level of E=0.44 mJ/mm2, which can therefore
      be recommended.

PMID- 15480644
TI  - Erdheim-Chester disease in a child with MR imaging showing regression of marrow
      changes.
AB  - OBJECTIVE: Erdheim-Chester disease is a disseminated xanthogranulomatous
      infiltrative disease of unknown origin that generally presents in adulthood. A
      review of the English-language literature demonstrated that pediatric cases were
      extremely rare, and to our knowledge, only two cases, a 7- and 14-year-old, have
      been published. DESIGN AND PATIENT: We report a case of Erdheim-Chester disease
      in a 10-year-old girl evaluated with MR imaging. Radiographs revealed typical
      bilateral, symmetric osteosclerosis of the metaphyseal regions of long bones of
      the upper and lower extremities. RESULTS: A histologic examination demonstrated
      foamy histiocytes in bone marrow smears. Bilateral symmetric low signal
      intensities of both proximal tibiae and distal femurs were demonstrated on T1
      weighted MR images. After oral steroid therapy for 8 months, follow-up MR imaging
      showed remarkable restoration of normal high signal intensity in both the tibial
      and femoral metaphyses. CONCLUSION: To our knowledge, this may be the first case
      of Erdheim-Chester disease that showed normal restoration of the abnormal signal
      intensities in the metaphyses of long bones after steroid therapy.

PMID- 15480645
TI  - Peripheral nerve schwannoma: two cases exhibiting increased FDG uptake in early
      and delayed PET imaging.
AB  - We present two cases of peripheral nerve schwannoma which showed an increased
      accumulation of 2-deoxy-[(18)F] fluoro-D-glucose (FDG) in the tumors on positron
      emission tomography (PET) imaging acquired at both 1 h (early phase) and 2 h
      (delayed phase) after FDG injection. FDG-PET scans were performed with a
      dedicated PET scanner (HeadtomeV/ SET2400 W, Shimadzu, Kyoto, Japan) and the PET
      data analyzed the most metabolically active region of interest (ROI). We set the
      maximum standardized uptake value (SUV max) with a cut-off point of 3.0 to
      distinguish benign and malignant lesions. Although the mechanism responsible for
      the increased FDG uptake in benign schwannomas remains unknown, we discuss our
      findings in the context of tumor cellularity and briefly review other studies on
      the subject.

PMID- 15480646
TI  - High signal intensity of intervertebral calcified disks on T1-weighted MR images
      resulting from fat content.
AB  - OBJECTIVE: To explain a cause of high signal intensity on T1-weighted MR images
      in calcified intervertebral disks associated with spinal fusion. DESIGN AND
      PATIENTS: Magnetic resonance and radiological examinations of 13 patients were
      reviewed, presenting one or several intervertebral disks showing a high signal
      intensity on T1-weighted MR images, associated both with the presence of
      calcifications in the disks and with peripheral fusion of the corresponding
      spinal segments. Fusion was due to ligament ossifications (n=8), ankylosing
      spondylitis (n=4), or posterior arthrodesis (n=1). Imaging files included X-rays
      and T1-weighted MR images in all cases, T2-weighted MR images in 12 cases, MR
      images with fat signal suppression in 7 cases, and a CT scan in 1 case.
      Histological study of a calcified disk from an anatomical specimen of an
      ankylosed lumbar spine resulting from ankylosing spondylitis was examined.
      RESULTS: The signal intensity of the disks was similar to that of the bone marrow
      or of perivertebral fat both on T1-weighted MR images and on all sequences,
      including those with fat signal suppression. In one of these disks, a strongly
      negative absorption coefficient was focally measured by CT scan, suggesting a
      fatty content. The histological examination of the ankylosed calcified disk
      revealed the presence of well-differentiated bone tissue and fatty marrow within
      the disk. CONCLUSION: The high signal intensity of some calcified intervertebral
      disks on T1-weighted MR images can result from the presence of fatty marrow,
      probably related to a disk ossification process in ankylosed spines.

PMID- 15480647
TI  - Calcific tendonitis of pectoralis major: CT and MRI findings.
AB  - OBJECTIVE: The shoulder is the most common location for calcific tendonitis.
      Presentation of calcific tendonitis at other sites is unusual and may lead to
      diagnostic difficulty. DESIGN AND PATIENTS: We report a case of calcific
      tendonitis of the pectoralis major insertion and describe the CT and MRI
      findings. RESULTS AND CONCLUSION: The presence of an associated cortical defect
      at the site of tendon insertion may lead to the incorrect diagnosis of neoplastic
      process.

PMID- 15480648
TI  - Sacrococcygeal chordoma: MR imaging in 30 patients.
AB  - OBJECTIVE: To evaluate MR imaging of sacrococcygeal chordoma. DESIGN AND
      PATIENTS: Thirty patients (age range 22-80 years) underwent MR imaging for the
      diagnosis and preoperative evaluation of sacrococcygeal chordomas. Eight patients
      had follow-up MR examination after treatment. The MR images were performed with
      T1- and T2-weighted imaging, and gadolinium (Gd)-enhanced imaging. The MR images
      were analyzed for the signal intensity, enhancing pattern, tumor size, growth
      pattern of the soft tissue component, and tumor extension. RESULTS AND
      CONCLUSIONS: T1-weighted images showed low signal masses with foci of high signal
      intensity in 73% of cases. Tumors enhanced in a variety of patterns after the
      administration of Gd. Soft tissue masses extending anteriorly were seen in all
      cases with posterior extension in 77% of cases. The posterior masses involved the
      surrounding muscles and extended toward the greater sciatic notch, appearing with
      pseudopodia (87%). Sacroiliac joints were involved in 23% of cases. Four lesions
      showed intraspinal extension and involvement of the posterior spinal muscles
      above the level of bony involvement. In 6 patients recurrent tumors were found at
      or around the surgical margin of the tumor 6 months to 5 years after resection of
      the sacral tumor. In two of the patients, nodular metastases to the pelvic bones
      and femur were found 1-4 years after initial examination. In conclusion, MR
      imaging is useful in the diagnosis and preoperative assessment of sacrococcygeal
      chordoma. Characteristic findings included sacral mass with heterogeneously high
      signal intensity with crisscrossing septa on long-repetition-time imaging, well
      encapsulated pseudopodia-like or lobulated appearance, and gluteal muscle
      infiltration. Follow-up MR imaging is helpful to assess for recurrent or
      metastatic lesions of chordomas.

PMID- 15480649
TI  - MRI assessment of knee osteoarthritis: Knee Osteoarthritis Scoring System (KOSS)-
      inter-observer and intra-observer reproducibility of a compartment-based scoring
      system.
AB  - OBJECTIVE: To develop a scoring system for quantifying osteoarthritic changes of
      the knee as identified by magnetic resonance (MR) imaging, and to determine its
      inter- and intra-observer reproducibility, in order to monitor medical therapy in
      research studies. DESIGN AND PATIENTS: Two independent observers evaluated 25
      consecutive MR examinations of the knee in patients with previously defined
      clinical symptoms and radiological signs of osteoarthritis. We acquired on a 1.5
      T system: coronal and sagittal proton density- and T2-weighted dual spin echo
      (SE) images, sagittal three-dimensional T1-weighted gradient echo (GE) images
      with fat suppression, and axial dual turbo SE images with fat suppression. Images
      were scored for the presence of cartilaginous lesions, osteophytes, subchondral
      cysts, bone marrow edema, and for meniscal abnormalities. Presence and size of
      effusion, synovitis and Baker's cyst were recorded. All parameters were ranked on
      a previously defined, semiquantitative scale, reflecting increasing severity of
      findings. Kappa, weighted kappa and intraclass correlation coefficient (ICC) were
      used to determine inter- and intra-observer variability. RESULTS: Inter-observer
      reproducibility was good (ICC value 0.77). Inter- and intra-observer
      reproducibility for individual parameters was good to very good (inter-observer
      ICC value 0.63-0.91; intra-observer ICC value 0.76-0.96). CONCLUSION: The
      presented comprehensive MR scoring system for osteoarthritic changes of the knee
      has a good to very good inter-observer and intra-observer reproducibility. Thus
      the score form with its definitions can be used for standardized assessment of
      osteoarthritic changes to monitor medical therapy in research studies.

PMID- 15480650
TI  - Maximising the benefit of integrated PET/CT: the road ahead.

PMID- 15480657
TI  - A polytope DNA vaccine elicits multiple effector and memory CTL responses and
      protects against human papillomavirus 16 E7-expressing tumour.
AB  - Vaccine-induced CD8 T cells directed to tumour-specific antigens are recognised
      as important components of protective and therapeutic immunity against tumours.
      Where tumour antigens have pathogenic potential or where immunogenic epitopes are
      lost from tumours, development of subunit vaccines consisting of multiple
      individual epitopes is an attractive alternative to immunising with whole tumour
      antigen. In the present study we investigate the efficacy of two DNA-based
      multiepitope ('polytope') vaccines containing murine (H-2b) and human (HLA
      A*0201)-restricted epitopes of the E7 oncoprotein of human papillomavirus type
      16, in eliciting tumour-protective cytotoxic T-lymphocyte (CTL) responses. We
      show that the first of these polytopes elicited powerful effector CTL responses
      (measured by IFN-gamma ELISpot) and long-lived memory CTL responses (measured by
      functional CTL assay and tetramers) in immunised mice. The responses could be
      boosted by immunisation with a recombinant vaccinia virus expressing the
      polytope. Responses induced by immunisation with polytope DNA alone partially
      protected against infection with recombinant vaccinia virus expressing the
      polytope. Complete protection was afforded against challenge with an E7
      expressing tumour, and reduced growth of nascent tumours was observed. A second
      polytope differing in the exact composition and order of CTL epitopes, and
      lacking an inserted endoplasmic reticulum targeting sequence and T-helper
      epitope, induced much poorer CTL responses and failed to protect against tumour
      challenge. These observations indicate the validity of a DNA polytope vaccine
      approach to human papillomavirus E7-associated carcinoma, and underscore the
      importance of design in polytope vaccine construction.

PMID- 15480658
TI  - Distal forearm tourniquet for hand surgery.
AB  - To evaluate the usefulness of the tourniquet placed at the distal forearm, 30
      patients were operated with the tourniquet set at the distal forearm using nerve
      block anaesthesia. Pain during surgery, flexion of the fingers, bloodless field,
      and general complications during surgery and 18 months thereafter were recorded.
      The mean time of ischemia was 19.6+/-7.5 (10-50) min. A bloodless field was
      achieved in all cases, and pain during operation was low. Flexion of the fingers
      were found in most cases but was reducible and not annoying for the surgeon.
      There were no serious complications during surgery or at follow-up. The
      tourniquet placed at the distal forearm is painless, safe, and useful in hand
      surgery.

PMID- 15480659
TI  - Patient-perceived outcome measures following unicompartmental knee arthroplasty
      with mini-incision.
AB  - We reviewed 150 patients (183 knees) who underwent mini-incision unicompartmental
      knee arthroplasty (Oxford). Mean age was 71.5 (36-92) years. Review was conducted
      at least 12 months following surgery. To assess results, we used the Oxford knee
      questionnaire, modified Grimby score, return to sport and work, knee "normality"
      and patient general health. The mean Oxford knee score was 22.17 (range 12-54).
      Kneeling scored worse than other activities. No significant age or gender
      difference was found. Mean modified Grimby score was 3.89, equating to moderate
      exercise less than 2 h a week. Patients with "artificial-feeling" knees had
      significantly worse scores than patients with normal/near-normal-feeling knees.
      Patients who returned to/increased sporting activity had better Oxford scores
      than those who did not. Ninety-four percent of patients working pre-operatively
      returned to work. Sixty-seven percent continued at the same level of or increased
      sporting activity. Oxford knee scores and return to sport compared well to
      published data. Results regarding modified Grimby score, return to work and pain
      relief were encouraging. The best results were achieved in active patients who
      felt their health was good and their knee felt normal or near normal following
      surgery.

PMID- 15480660
TI  - Results after anterior-posterior lumbar spinal fusion: 2-5 years follow-up.
AB  - Between 1991 and 1998, we treated 72 patients with fusion of the lumbar spine
      using posterior pedicle screw fixation followed by anterior retroperitoneal
      insertion of a titanium cage filled with autogenous bone graft. All patients had
      chronic low back pain after failed conservative treatment. We were able to review
      54 patients with a mean follow-up of 51 (24-97) months. The mean Oswestry low
      back pain disability score improved from 56.8 preoperative to postoperative 29.8
      and 31.2 at follow-up (p<0.05). The mean visual analog pain intensity scale
      improved from 8.3 to 4.0 postoperative and 4.8 at follow-up (p<0.05). The results
      demonstrate that circumferential lumbar fusion can be an option for the treatment
      of chronic low back pain.

PMID- 15480661
TI  - Cadaveric allograft microbiology.
AB  - This study aims to determine the contamination rate of cadaveric bone allograft
      and blood cultures retrieved from 119 donors within Leicester between 1990 and
      2003. A contamination rate of 27% was present, with 120 of 437 bone allografts
      culturing positive at the time of retrieval. Similarly, a contamination rate of
      37% was present, with 40 of 107 blood samples culturing positive. The time
      interval between death and procurement did not influence blood contamination.
      Coagulase-negative Staphylococcus was the commonest organism isolated in both
      blood and bone cultures. One donor had Clostridium grown in their blood culture.
      The available evidence confirms similar contamination rates with other studies.
      The majority of organisms isolated were skin commensals with a low rate of
      contamination of highly pathogenic organisms such as Clostridium.

PMID- 15480662
TI  - Bone allografting: an Indian experience.
AB  - Freeze-drying is considered to be the best technique for allograft preparation
      and storage. This method is, however, unsuitable for use in developing countries
      due to high costs. Ethylene oxide sterilization is still controversial because of
      its effect on osteoinductive capacity. This study involved setting up a bone bank
      for the first time. Cancellous bone collected from 40 patients was cleaned
      thoroughly, chemically processed, and sterilized with ethylene oxide gas and
      stored doubly packed. The grafts were implanted in 11 patients with 14 nonunions.
      Patients were followed up clinically and radiologically. Thirteen sites were
      united at the end of 12 months, taking an average of 44.8 weeks to unite.
      Allograft was also used in 8 benign bone lesions, which showed incorporation of
      the graft by 29 weeks. This study shows cancellous allograft is suitable for
      packing cavities in the treatment of benign bone lesions and in treatment of
      nonunion. There was one deep infection. The low infection rate confirms the
      efficacy of ethylene oxide as a reliable option for sterilization of bone
      allograft, and it is also cost effective.

PMID- 15480663
TI  - Epidemiology of non-Hodgkin's lymphoma (NHL): trends, geographic distribution,
      and etiology.
AB  - While for most cancers incidence and mortality are decreasing, those of non
      Hodgkin's lymphoma (NHL) are steadily increasing. Research to define reasons for
      this increase is extensive, but has not yet resolved them. We have conducted a
      literature analysis on trends regarding changes in the incidence, geographic
      distribution, and etiologic factors of NHL. From our own and previous analyses,
      an increasing NHL incidence at a rate of 3-4% per year was observed for the 1970s
      and 1980s. This stabilized in the 1990s, nevertheless still with an annual rise
      of 1-2%, resulting in almost a doubling of the NHL incidence. This rise has been
      noted worldwide, particularly in elderly persons >55 years. Concerning gender
      subgroups, a male predominance throughout all age groups is apparent. Although
      the NHL incidence has historically been higher in whites than blacks,
      disproportional increases have recently been observed in the latter group.
      Increases in high-grade NHL and extranodal disease are predominant. Differences
      in geographic distribution are striking for follicular lymphoma, which is more
      common in Western countries than elsewhere. Asians have higher rates of
      aggressive NHL, T-cell lymphomas, and extranodal disease. In the Middle East,
      high rates of intestinal extranodal disease are observed, whereas in Africa,
      endemic Burkitt's lymphoma accounts for a substantial proportion. Risks for
      developing NHL include immunosuppression and a causal link between infectious
      agents, and lymphomagenesis has also been determined, particularly for human T
      cell leukemia/lymphoma virus type 1 (HTLV-1), Epstein-Barr virus (EBV), and
      Helicobacter pylori infections. Exposure to environmental agents and occupational
      risks have been studied; however, their significance is as yet uncertain.

PMID- 15480664
TI  - Sodium selenite induces apoptosis in acute promyelocytic leukemia-derived NB4
      cells by a caspase-3-dependent mechanism and a redox pathway different from that
      of arsenic trioxide.
AB  - Two relatively recent discoveries stand behind our current effort to investigate
      the effects of the chemopreventive agent, selenium, on the proliferation and
      survival of NB4 cells. The first is that certain selenium compounds such as
      sodium selenite have pro-oxidant ability to catalyze the oxidation of thiols and
      simultaneously generate superoxide. The second lies in the exquisite
      susceptibility of NB4 cells to arsenic trioxide-induced, reactive oxygen species
      (ROS)-mediated apoptosis due to less efficiency of the cellular defense system.
      In this study, we demonstrated that sodium selenite could induce apoptosis in NB4
      cells via the classic mitochondrial pathway involving caspase-3 activation and
      Bcl-2 cleavage. An increase in the basal cellular glutathione (GSH) content
      rendered NB4 cells resistant to arsenic trioxide, but could sensitize NB4 cells
      to sodium selenite. Moreover, combined treatment of NB4 cells with all- trans
      retinoic acid (ATRA) at low concentration and sodium selenite exhibited a
      synergistic effect on apoptosis induction. Together, our results suggest that
      selenite is a promising candidate for treatment of acute promyelocytic leukemia
      (APL) and the mechanism underlying its anticancer effects warrants further
      investigation.

PMID- 15480665
TI  - Bacterial and fungal bloodstream isolates from 796 hematopoietic stem cell
      transplant recipients between 1991 and 2000.
AB  - To examine shifts in the etiology, incidence, evolution, susceptibility, and
      patient mortality of bacterial and fungal bloodstream isolates (BSIs) from
      hematopoietic stem cell transplantation (HSCT) recipients, we reviewed the BSIs
      of 796 patients who underwent an HSCT in our institution during a 10-year period.
      Four hundred eighty-nine episodes of bacterial and fungal BSI were detected in
      330 patients (41%). Three hundred ten isolates (63%) were gram-positive bacteria,
      142 (29%) were gram-negative, and 18 and 19 isolates were different species of
      anaerobic organism and Candida spp. (both 4%). Coagulase-negative staphylococci
      (CoNS), with 210 isolates, were the organism most frequently isolated in each
      year of study and during the three phases of immune recovery after HSCT. The
      ratio of gram-positive to gram-negative has declined from 3.3 (1991-1992) to 1.8
      (1999-2000). Crude mortality occurred in 47 cases of 489 BSI episodes (10%).
      Mortality according to groups was gram-negative, 7%; gram-positive, 9%; and
      anaerobic bacteria, 11%. Candida spp. was the group that accounted for the
      highest crude mortality, with 42%. Gram-positive microorganisms were isolated
      more often than gram-negative organisms, but the trend is reversing. CoNS were
      the leading pathogen during the 10 years of study and during the three phases of
      immune recovery after HSCT. Crude mortality of HSCT patients with BSI was low
      except for infections caused by Candida spp.

PMID- 15480669
TI  - A cardiovascular-respiratory control system model including state delay with
      application to congestive heart failure in humans.
AB  - This paper considers a model of the human cardiovascular-respiratory control
      system with one and two transport delays in the state equations describing the
      respiratory system. The effectiveness of the control of the ventilation rate is
      influenced by such transport delays because blood gases must be transported a
      physical distance from the lungs to the sensory sites where these gases are
      measured. The short term cardiovascular control system does not involve such
      transport delays although delays do arise in other contexts such as the
      baroreflex loop (see [46]) for example. This baroreflex delay is not considered
      here. The interaction between heart rate, blood pressure, cardiac output, and
      blood vessel resistance is quite complex and given the limited knowledge
      available of this interaction, we will model the cardiovascular control mechanism
      via an optimal control derived from control theory. This control will be
      stabilizing and is a reasonable approach based on mathematical considerations as
      well as being further motivated by the observation that many physiologists cite
      optimization as a potential influence in the evolution of biological systems
      (see, e.g., Kenner [29] or Swan [62]). In this paper we adapt a model, previously
      considered (Timischl [63] and Timischl et al. [64]), to include the effects of
      one and two transport delays. We will first implement an optimal control for the
      combined cardiovascular-respiratory model with one state space delay. We will
      then consider the effects of a second delay in the state space by modeling the
      respiratory control via an empirical formula with delay while the the complex
      relationships in the cardiovascular control will still be modeled by optimal
      control. This second transport delay associated with the sensory system of the
      respiratory control plays an important role in respiratory stability. As an
      application of this model we will consider congestive heart failure where this
      transport delay is larger than normal and the transition from the quiet awake
      state to stage 4 (NREM) sleep. The model can be used to study the interaction
      between cardiovascular and respiratory function in various situations as well as
      to consider the influence of optimal function in physiological control system
      performance.

PMID- 15480670
TI  - On the stability of a model of testosterone dynamics.
AB  - We prove the global asymptotic stability of a well-known delayed negative
      feedback model of testosterone dynamics, which has been proposed as a model of
      oscillatory behavior. We establish stability (and hence the impossibility of
      oscillations) even in the presence of delays of arbitrary length.

PMID- 15480668
TI  - Autologous stem cell transplantation in hematological malignancies.

PMID- 15480671
TI  - State-dependent impulsive models of integrated pest management (IPM) strategies
      and their dynamic consequences.
AB  - A state-dependent impulsive model is proposed for integrated pest management
      (IPM). IPM involves combining biological, mechanical, and chemical tactics to
      reduce pest numbers to tolerable levels after a pest population has reached its
      economic threshold (ET). The complete expression of an orbitally asymptotically
      stable periodic solution to the model with a maximum value no larger than the
      given ET is presented, the existence of which implies that pests can be
      controlled at or below their ET levels. We also prove that there is no periodic
      solution with order larger than or equal to three, except for one special case,
      by using the properties of the LambertW function and Poincare map. Moreover, we
      show that the existence of an order two periodic solution implies the existence
      of an order one periodic solution. Various positive invariant sets and attractors
      of this impulsive semi-dynamical system are described and discussed. In
      particular, several horseshoe-like attractors, whose interiors can simultaneously
      contain stable order 1 periodic solutions and order 2 periodic solutions, are
      found and the interior structure of the horseshoe-like attractors is discussed.
      Finally, the largest invariant set and the sufficient conditions which guarantee
      the global orbital and asymptotic stability of the order 1 periodic solution in
      the meaningful domain for the system are given using the Lyapunov function. Our
      results show that, in theory, a pest can be controlled such that its population
      size is no larger than its ET by applying effects impulsively once, twice, or at
      most, a finite number of times, or according to a periodic regime. Moreover, our
      theoretical work suggests how IPM strategies could be used to alter the levels of
      the ET in the farmers' favour.

PMID- 15480672
TI  - Model selection and parameter estimation for ion channel recordings with an
      application to the K+ outward-rectifier in barley leaf.
AB  - We present a statistical method, and its accompanying algorithms, for the
      selection of a mathematical model of the gating mechanism of an ion channel and
      for the estimation of the parameters of this model. The method assumes a hidden
      Markov model that incorporates filtering, colored noise and state-dependent white
      excess noise for the recorded data. The model selection and parameter estimation
      are performed via a Bayesian approach using Markov chain Monte Carlo. The method
      is illustrated by its application to single-channel recordings of the K(+)
      outward-rectifier in barley leaf.

PMID- 15480673
TI  - Derivation of hyperbolic models for chemosensitive movement.
AB  - A Chapman-Enskog expansion is used to derive hyperbolic models for chemosensitive
      movements as a hydrodynamic limit of a velocity-jump process. On the one hand, it
      connects parabolic and hyperbolic chemotaxis models since the former arise as
      diffusion limits of a similar velocity-jump process. On the other hand, this
      approach provides a unified framework which includes previous models obtained by
      ad hoc methods or methods of moments. Numerical simulations are also performed
      and are motivated by recent experiments with human endothelial cells on matrigel.
      Their movements lead to the formation of networks that are interpreted as the
      beginning of a vasculature. These structures cannot be explained by parabolic
      models but are recovered by numerical experiments on hyperbolic models. Our
      kinetic model suggests that some kind of local interactions might be enough to
      explain them.

PMID- 15480674
TI  - Spatial effects in discrete generation population models.
AB  - A framework is developed for constructing a large class of discrete generation,
      continuous space models of evolving single species populations and finding their
      bifurcating patterned spatial distributions. Our models involve, in separate
      stages, the spatial redistribution (through movement laws) and local regulation
      of the population; and the fundamental properties of these events in a
      homogeneous environment are found. Emphasis is placed on the interaction of
      migrating individuals with the existing population through conspecific attraction
      (or repulsion), as well as on random dispersion. The nature of the competition of
      these two effects in a linearized scenario is clarified. The bifurcation of
      stationary spatially patterned population distributions is studied, with special
      attention given to the role played by that competition.

PMID- 15480675
TI  - [Forensic DNA-analysis in pathology].
AB  - The principles of modern forensic DNA-analysis using the amplification of so
      called STR-polymorphisms are explained. Four cases from practise that required
      the collaboration of forensic molecular biology and pathology and which were
      analysed by them are presented and discussed. Similarities and variations in the
      work of both "disciplines" are presented and suggestions for the storage of
      samples formulated.

PMID- 15480676
TI  - Agrobacterium tumefaciens-mediated transformation of the antitumor clavaric acid
      producing basidiomycete Hypholoma sublateritium.
AB  - The basidiomycete Hypholoma sublateritium produces clavaric acid, an antitumor
      isoprenoid compound. Arthrospores of this fungus were transformed by
      Agrobacterium tumefaciens-mediated conjugation. Five plasmids carrying different
      regulatory sequences to drive expression of the hph (hygromycin
      phosphotransferase) gene were tested. The promoter used was critically important
      in order to express heterologous genes in H. sublateritium. Constructions
      carrying the Agaricus bisporus glyceraldehyde-3-phosphate dehydrogenase promoter
      (P gpd) showed a good transformation efficiency, whereas constructions with the
      gpd promoter from ascomycetes were ineffective. Transformant clones showed a
      random integration pattern of plasmid DNA. Most transformants showed a single
      integrated copy of the transforming plasmid, but about 1.5% showed double or
      multiple integrations. All the analyzed transformants were mitotically stable and
      maintained the integrated exogenous DNA in the absence of antibiotic. The green
      fluorescent protein gene was expressed from the A. bisporus gpd promoter, as
      shown by RT-PCR studies, but no significant fluorescence was observed.
      Transformation of H. sublateritium opens the way for the genetic manipulation of
      clavaric acid biosynthesis in this fungus.

PMID- 15480678
TI  - Transdermal fentanyl for the treatment of pain caused by rheumatoid arthritis.
AB  - This study evaluated transdermal fentanyl (TDF) for the treatment of pain from
      rheumatoid arthritis (RA) which was not adequately controlled by nonopioid
      analgesics and/or weak opioids. Following 1 week of optimization of current
      analgesic medication, patients (n = 104) started 28-day treatment with 25
      microg/h of TDF, with the option to up-titrate until adequate pain control was
      achieved. Metoclopramide was taken during the 1st week and as needed thereafter.
      Eighty-four patients completed the treatment phase, and 42 entered the 1-week
      tapering-off phase. The most frequently used maximum dose was 25 microg/h. The
      number of patients with pain control increased, particularly in the 1st week of
      treatment (33% to 77%), to 88% on day 28. From baseline to endpoint, there were
      reductions in pain (P < 0.001), including in "pain right now" at 24 h, and in
      degree of pain (mean reduction from "severe" to "moderate"), improvements in
      function (majority of items in the Health Assessment Questionnaire) (P < 0.001),
      and in quality of life (Short Form 36 physical P < 0.001, mental P < 0.05).
      Treatment was assessed favorably: > or = 78% would recommend it. Transdermal
      fentanyl should be considered in treatment programs for patients with RA.

PMID- 15480677
TI  - Cell wall-degrading isoenzyme profiles of Trichoderma biocontrol strains show
      correlation with rDNA taxonomic species.
AB  - Trichoderma is known for being the most frequently used biocontrol agent in
      agriculture. A fundamental part of the Trichoderma antifungal system relies on a
      series of genes coding for a variety of extracellular lytic enzymes.
      Characterization of the polymorphism between five putative isoenzymatic
      activities [beta-1,3-glucanase (EC 3.2.1.39, EC 3.2.1.58), beta-1,6-glucanase (EC
      3.2.1.75), cellulase (EC 3.2.1.4; EC 3.2.1.21, EC 3.2.1.91), chitinase (EC
      3.2.1.30, EC 3.2.1.52), protease (EC 3.4.11; EC 3.4.13-19; EC 3.4.21-24, EC
      3.4.99)] was carried out using 18 strains from three sections of Trichoderma. Of
      these, seven strains were from T. sect. Pachybasium, nine from T. sect.
      Trichoderma and two from T. sect. Longibrachiatum. Thirty-seven different alleles
      in total were identified: 13 for beta-1,3-glucanase, four for beta-1,6-glucanase,
      three for cellulase, eight for chitinase and nine for protease activity. A
      dendrogram (constructed by the unweighted pair group method with arithmetic
      averages) based on isoenzymatic data separated the 18 strains into three main
      enzymatic groups: T. harzianum, T. atroviride/T. viride/T. koningii and T.
      asperellum/T. hamatum/T. longibrachiatum. Isoenzymatic groupings obtained from
      biocontrol strains are discussed in relation to their phylogenetic location,
      based on their sequence of internal transcribed spacer 1 in ribosomal DNA and
      their antifungal activities.

PMID- 15480679
TI  - Osteopenia in men with mild and severe ankylosing spondylitis.
AB  - We investigated the frequency and distribution of osteopenia according to the
      clinical severity in ankylosing spondylitis (AS). Bone mass was measured in men
      with mild (n = 45) and severe AS (n = 31) with dual-energy X-ray absorptiometry
      (DEXA). Definition of clinical severity was based on the Schober's test.
      Osteopenia was commonly detected (48% in mild AS and 39% severe AS) and, in mild
      disease, more frequently observed at the lumbar spine than any of the proximal
      femur sites. In severe AS, however, the frequency of osteopenia at the femoral
      neck and Ward's triangle was as high as at the lumbar spine. Both bone mineral
      density and T-scores in severe disease were lower than in mild disease at the
      femur neck, Ward's triangle, and total proximal femur, but not in the lumbar
      spine. The progression of osteopenia may be reflected more reliably at proximal
      femur sites than at the lumbar spine.

PMID- 15480680
TI  - An efficient method for flow cytometric analysis of pollen and detection of 2n
      nuclei in Brassica napus pollen.
AB  - A simple and reliable method was developed for isolating pollen nuclei from
      Brassica napus and Triticum aestivum for DNA analysis using flow cytometry. The
      nuclei were released from pollen by ultrasonic treatment. The isolated nuclei
      following filtration through nylon mesh and a purification procedure were
      suitable for flow cytometric analysis as well as for isolating genomic DNA.
      Ultrasonic treatment time was optimized for B. napus pollen at different
      developmental stages. The method is effective and suitable for the preparation of
      many samples. We analyzed the nuclear DNA levels in pollen of B. napus at three
      major developmental stages as well as in mature wheat pollen. Only a single 1C
      peak representing the haploid DNA level was detected in the nuclei isolated from
      Brassica uninucleate microspores as well as in mature Triticum pollen.
      Interestingly, diploid nuclei were detected in both binucleate and mature pollen
      of B. napus. The possible origins of the diploid nuclei are discussed.

PMID- 15480681
TI  - Aminooxyacetic acid inhibits antheridiogenesis and development of Anemia
      phyllitidis gametophytes.
AB  - Cytomorphological studies of the development of young fern gametophytes (Anemia
      phyllitidis) have been used to investigate combined effects of gibberellic acid
      and ethylene on male sex expression. ACC (the key by-product in ethylene
      biosynthesis pathway) was found to exert a synergetic effect on the gibberellic
      acid-induced antheridia formation, and this phenomenon could be related with the
      specific stimulation of cell growth and activity of their differentiation. To
      complete and verify those observations male sex expression in the fern
      gametophytes treated with ACC-biosynthesis inhibitor was reinvestigated.
      Aminooxyacetic acid (AOA) restrained antheridia formation via inhibition of cell
      divisions. AOA influenced the arrangement and flexibility of cellulose
      microfibrils in the antheridial zone cells, thus affecting cell expansion. On the
      other hand, the level of DNA synthesis was not reduced. Transient increase in the
      number of S-phase cells, followed by the accumulation of G2-phase cells led to
      the enhancement of cell polyploidization. All these findings correspond with the
      previous observations and support participation of ethylene in gibberellic acid
      induced male sex expression in ferns.

PMID- 15480682
TI  - Transgenic Gladiolus plants transformed with the bean yellow mosaic virus coat
      protein gene in either sense or antisense orientation.
AB  - Transgenic Gladiolus plants transformed with the bean yellow mosaic virus (BYMV)
      coat-protein (CP) gene in either sense or antisense (AS) orientation were
      developed using biolistics. Four of the plants were confirmed to carry the CP
      gene in the sense orientation of the gene and seven plants in the AS orientation.
      Two of the CP plant lines and all of the AS lines showed DNA rearrangements of
      the transgene in addition to an intact copy of the transgene. The copy number
      ranged from one to nine. Of the 11 lines, eight had only one to four copies of
      the transgene. Transcription of the transgene occurred for three of the CP lines
      and five of the AS lines as determined by Northern hybridization. All 11 plant
      lines were challenged with BYMV using controlled aphid transmission. One month
      following aphid transmission, the transgenic plants were examined by
      immunoelectron microscopy for presence of the virus. Several transgenic plant
      lines containing either antiviral transgene showed a lower incidence of infection
      (percentage of plants infected as detected by immunoelectron microscopy) than the
      non-transformed plants. Most of the CP- and AS-transgenic plants that did not
      contain BYMV 1 month after challenge were found to contain BYMV the next season.
      It appeared that BYMV infection was delayed in the CP- and AS-transgenic lines
      but that the transgenes did not prevent eventual infection of BYMV. This is the
      first report of developing a floral bulb crop with antiviral genes to BYMV.

PMID- 15480683
TI  - Evaluation of 12 beta-lactam antibiotics for Agrobacterium-mediated
      transformation through in planta antibacterial activities and phytotoxicities.
AB  - The antibacterial activities of 12 beta-lactam antibiotics against Agrobacterium
      tumefaciens strains LBA4404 and EHA101 living in tobacco (Nicotiana tabacum L.)
      leaf tissues, and their phytotoxicities to tobacco leaf tissues were evaluated.
      All beta-lactams at minimum bactericidal concentration (MBC) or higher showed
      weak bactericidal activities against agrobacteria persisting in tobacco leaf
      tissues. The beta-lactams evaluated were classified into two major groups
      according to their inhibitory effect on shoot regeneration of tobacco leaf
      tissues: (1) highly phytotoxic drugs, and (2) moderately phytotoxic drugs.
      According to these results, suitable kind and concentration of beta-lactam
      antibiotics were evaluated for Agrobacterium-mediated transformation.

PMID- 15480684
TI  - Characterisation of the Dunaliella tertiolecta RbcS genes and their promoter
      activity in Chlamydomonas reinhardtii.
AB  - The availability of highly active homologous promoters and terminators is
      critical in the development of a transformation system for the unicellular
      microalga Dunaliella tertiolecta. To facilitate transformation of this species,
      we isolated and characterised two native ribulose-1,5-bisphosphate
      carboxylase/oxygenase small subunit genes (RbcS) including flanking sequences.
      The two non-allelic cDNA sequences share approximately 80% identity and have
      approximately 60% identity to the RbcS genes of Chlamydomonas reinhardtii. The D.
      tertiolecta RbcS promoter and 3' untranslated regions were shown to drive
      expression of the bleomycin resistance gene (ble) in C. reinhardtii. This is the
      first demonstration of a heterologous algal promoter being used to drive
      transgene expression in C. reinhardtii. In addition, promoter deletions were
      shown to further increase transformation efficiency.

PMID- 15480685
TI  - Utility of the FLP-FRT recombination system for genetic manipulation of rice.
AB  - To develop an FLP-FRT recombination system- (derived from 2 mu plasmid of
      Saccharomyces cerevisiae) based marker gene removal application for rice, we
      introduced the gene for FLP recombinase, under the control of the maize ubiquitin
      1 promoter, into the rice genome. FLP activity was monitored in callus and
      regenerated plants by an assay based on the deletion of the FRT-flanked DNA
      fragment, leading to the activation of the beta-glucuronidase gene. FLP activity
      was detected both in the callus and leaves of some of the transgenic lines. Based
      on our comparison of the recombination efficiency of the FLP-FRT system expressed
      in the transgenic lines with that of the widely used Cre-lox system (derived from
      bacteriophage P1), we suggest that the FLP-FRT system is a useful tool for the
      genetic manipulation of rice.

PMID- 15480686
TI  - Agrobacterium-mediated transformation of bottle gourd (Lagenaria siceraria
      Standl.).
AB  - We describe a procedure for producing transgenic bottle gourd plants by
      inoculating cotyledon explants with Agrobacterium tumefaciens strain AGL1 that
      carries the binary vector pCAMBIA3301 containing a glufosinate ammonium
      resistance (bar) gene and the beta-D-glucuronidase (GUS) reporter gene. The most
      effective bacterial infection was observed when cotyledon explants of 4-day-old
      seedlings were co-cultivated with Agrobacterium for 6-8 days on co-cultivation
      medium supplemented with 0.1-0.001 mg/l L-alpha-(2-aminoethoxyvinyl) glycine
      (AVG). The putatively transformed shoots directly emerged at the proximal end of
      cotyledon explants after 2-3 weeks of culturing on selection medium containing 2
      mg/l DL-phosphinothricin. These shoots were rooted after 3 weeks of culturing on
      half-strength MS medium containing 0.1 mg/l indole acetic acid and 1 mg/l DL
      phosphinothricin. Transgenic plants were obtained at frequencies of 1.9%. Stable
      integration and transmission of the transgenes in T1 generation plants were
      confirmed by a histochemical GUS assay, polymerase chain reaction and Southern
      blot analyses. Genetic segregation analysis of T1 progenies showed that
      transgenes were inherited in a Mendelian fashion. To our knowledge, this study is
      the first to show Agrobacterium-mediated transformation in bottle gourd.

PMID- 15480687
TI  - Transgenic tall fescue containing the Agrobacterium tumefaciens ipt gene shows
      enhanced cold tolerance.
AB  - Embryogenic calli of Festuca arundinacea were transformed with the Agrobacterium
      tumefaciens isopentenyl transferase (ipt) gene driven by a maize ubiquitin
      promoter. Tillering ability, levels of chlorophyll a and b, and cold tolerance
      were greatly increased in the transgenic turfgrass, which resulted in the plants
      remaining more vigorous and staying green longer under lower temperatures.

PMID- 15480688
TI  - Liposarcoma subtypes: identification with computed tomography and ultrasound
      guided percutaneous needle biopsy.
AB  - The purpose of the study was to evaluate the feasibility of image-guided
      percutaneous needle biopsy to enable specific subtype classification of
      liposarcoma in patients with previously diagnosed disease and compare the yield
      of fine and large needle techniques for each subtype. We reviewed the medical
      records and pathology reports of 69 fine (20 g) needle and large (15, 16 g)
      needle biopsies performed in 44 patients enrolled in a clinical trial evaluating
      the effect of a novel therapy for advanced liposarcoma in the abdomen and pelvis.
      Cytopathologists and surgical pathologists identified features that enabled them
      to classify the tumor into one of four subtypes: well differentiated,
      myxoid/round cell, pleomorphic and dedifferentiated. The pre-study open surgical
      biopsy was used as the standard for comparison. The diagnostic yield (proportion
      of biopsies with correct subtype diagnosis) of percutaneous biopsy for
      identifying all subtypes of liposarcoma was 81% (64% for fine needles and 73% for
      large needles alone). There was a significant association between pathologic
      subtype and the probability of a correct diagnosis (P=0.05). Accurate diagnostic
      subset classification of liposarcoma by percutaneous biopsy is feasible, although
      both fine and large needles should be used. Although these data cannot be
      extrapolated to primary diagnosis of liposarcoma, they are important for
      screening and subtyping of possible recurrence.

PMID- 15480690
TI  - Visual stimulation, 1H MR spectroscopy and fMRI of the human visual pathways.
AB  - The purpose was to assess changes in lactate content and other brain metabolites
      under visual stimulation in optical chiasm, optic radiations and occipital cortex
      using multiple voxel MR spectroscopy (MRS). 1H chemical shift imaging (CSI)
      examinations of transverse planes centered to include the above structures were
      performed in four subjects at an echo time of 135 ms. Functional MRI (fMRI) was
      used to confirm the presence of activity in the visual cortex during the visual
      stimulation. Spectral maps of optical chiasm were of poor quality due to field
      disturbances caused by nearby large blood vessels and/or eye movements. The optic
      radiations and the occipital lobe did not show any significant MR spectral change
      upon visual stimulation, i.e., the peak areas of inositol, choline, creatine,
      glutamate and N-acetylaspartate were not affected. Reproducible lactate signals
      were not observed. fMRI confirmed the presence of strong activations in
      stimulated visual cortex. Prolonged visual stimulation did not cause significant
      changes in MR spectra. Any signal observed near the 1.33 ppm resonance frequency
      of the lactate methyl-group was artifactual, originating from lipid signals from
      outside the volume of interest (VOI). Previous claims about changes in lactate
      levels in the visual cortex upon visual stimulation may have been based on such
      erroneous observations.

PMID- 15480691
TI  - Multiplanar functional imaging of the larynx and hypopharynx with multislice
      spiral CT.
AB  - The purpose of this study is to evaluate multislice spiral CT (MSCT) in
      multiplanar functional imaging of the larynx and hypopharynx and to define the
      optimal image planes for the delineation of the tumor and specific anatomical
      structures. Forty patients with suspected tumors of the larynx or hypopharynx
      were examined with MSCT during quiet breathing (QB), E-phonation (EP) and
      modified Valsalva maneuver (VM). Images were read in the axial, coronal and
      sagittal planes. Overall image quality, delineation of the tumor and anatomic
      structures for different conditions and orientations were graded using a three
      point scale; the conditional permutation test was applied to detect quality
      differences. Differences between image types were statistically significant. The
      axial plane was superior in overall image quality and the delineation of the
      tumor, pyriform sinus, vocal cords and fat within the parapharyngeal/visceral
      space. The coronal plane was best for delineating the ventricle and the
      paraglottic space, the sagittal plane for the retropharyngeal and the
      preepiglottic space. For tumor detection, sensitivity, specificity and accuracy
      were 0.92, 1.0 and 0.93 for QB.ax, 0.94, 0.8 and 0.92 for EP.ax and 0.85, 1.0 and
      0.87 for VM.ax, respectively. Examination during QB should be the standard
      procedure; additional scanning with EP improved tumor assessment.

PMID- 15480689
TI  - Interventional and intraoperative MR: review and update of techniques and
      clinical experience.
AB  - The concept of interventional magnetic resonance imaging (MRI) is based on the
      integration of diagnostic and therapeutic procedures, favored by the combination
      of the excellent morphological and functional imaging characteristics of MRI. The
      spectrum of MRI-assisted interventions ranges from biopsies and intraoperative
      guidance to thermal ablation modalities and vascular interventions. The most
      relevant recently published experimental and clinical results are discussed. In
      the future, interventional MRI is expected to play an important role in
      interventional radiology, minimal invasive therapy and guidance of surgical
      procedures. However, the associated high costs require a careful evaluation of
      its potentials in order to ensure cost-effective medical care.

PMID- 15480692
TI  - Digital detectors for mammography: the technical challenges.
AB  - This paper reviews the different techniques available and competing for full
      field digital mammography. The detectors are described in their principles:
      photostimulable storage phosphor plates inserted as a cassette in a conventional
      mammography unit, dedicated active matrix detectors (i.e., flat-panel, thin-film
      transistor-based detectors) and scanning systems, using indirect and direct X-ray
      conversion. The main parameters that characterize the performances of the current
      systems and influence the quality of digital images are briefly explained:
      spatial resolution, detective quantum efficiency and modulation transfer
      function. Overall performances are often the result of compromises in the choice
      of technology.

PMID- 15480693
TI  - Truncus arteriosus communis in a midtrimester fetus: comparison of prenatal
      ultrasound and MRI with postmortem MRI and autopsy.
AB  - Different techniques are used in fetal cardiology, and their accuracy has been
      demonstrated on several occasions. Color Doppler US has proved to be a reliable
      and valuable tool in the diagnosis of fetal cardiac abnormalities. Magnetic
      resonance imaging (MRI) of the fetal heart has, so far, played no role in
      prenatal diagnostics. We report on a truncus arteriosus communis diagnosed
      prenatally during a screening ultrasound at 22 weeks of gestation. In addition to
      real-time ultrasound and color Doppler echocardiography, fetal MRI was performed.
      Fetal echocardiography arose suspicion of a type I common trunk. Fetal MR showed
      solely a widened vessel coursing retrocardially and additionally an inhomogeneous
      fluid distribution of the lung not shown on prenatal US. After termination of
      pregnancy at 23 weeks of gestation, MR fetography and autopsy were performed, and
      both found a type II common trunk. MR autopsy of the heart was very reliable in
      this case and could be an alternative when fetal pathology is not available for
      different reasons. Postmortem MRI was also able to demonstrate the inhomogeneous
      fluid distribution in the lung, which was confirmed by autopsy. Fetal and
      postmortem MR was reliable in the detection of an inhomogeneous fluid
      distribution in the lung not shown on prenatal US, providing a relevant
      additional finding to US. Therefore, MRI should be used more often in fetal
      cardiology, although it still must be further developed.

PMID- 15480694
TI  - Radiological features of adenoid cystic carcinoma of the uterine cervix.
AB  - Adenoid cystic carcinoma (ACC) of the uterine cervix is a rare primary neoplasm
      of the uterus that occurs in post-menopausal women; its radiological findings
      have not been described previously. We present the MR findings of a case of ACC.
      The mass exhibited homogeneous low-signal intensity on T1-weighted images. On T2
      weighted images, the mass showed high-signal intensity with a lobulated contour
      and multiple septum-like internal architectures. It also contained spots of very
      high-signal intensity, which would represent the mucin in the glandular lumen.
      The multiple septum-like internal architectures probably represented
      interglandular fibrous stroma. These MRI findings may be helpful for future
      diagnoses of ACC of the uterine cervix.

PMID- 15480697
TI  - [Unilateral facial swelling and vision impairment].

PMID- 15480696
TI  - Contrast specific imaging in the detection and localization of prostate cancer.
AB  - Prostate cancer (PCa) is the most common cancer in elderly men and is one of the
      most important causes of death from cancer in men. The diagnosis of PCa is based
      on a combination of digital rectal examination, PSA and transrectal ultrasound
      (TRUS). However, this combination does not reach the accuracy of detection and
      localization necessary for proper decisions on treatment methods. Therefore,
      biopsies are performed in all cases for which the suspicion of PCa is raised.
      Even with biopsies, staging and grading of PCa is far from optimal. More accurate
      imaging is necessary to improve the biopsy sampling, the goals being to replace
      systematic biopsies by a targeted approach and to improve staging and grading of
      PCa. Ultrasound imaging of the prostate remains the first choice of imaging to
      visualize the prostate, however, gray-scale ultrasound imaging has an accuracy of
      about 50-60% for the detection of PCa and TRUS used for local staging has an even
      lower accuracy. The development of PCa is associated with changes in the
      metabolism of tumor cells, and therefore with changes in the blood perfusion of
      the involved tissue. This paper focuses on contrast specific imaging techniques
      to visualize these changes in blood perfusion. Techniques such as color and power
      Doppler imaging, and contrast enhanced imaging techniques using color and power
      Doppler, harmonic imaging and intermittent imaging are discussed.

PMID- 15480695
TI  - Calcific myonecrosis: a report of ten new cases with an emphasis on MR imaging.
AB  - The aim of this study is to report the typical radiographic and MR imaging
      features of calcific myonecrosis, which help to distinguish this rare entity from
      other causes of a calcifying calf mass. Ten patients with a final diagnosis of
      calcific myonecrosis were referred to a specialist orthopaedic oncology service
      in a 5-year period with the presumptive diagnosis of malignancy based on recent
      clinical presentation and imaging findings. Radiographs were available for
      retrospective review in all ten cases and MR imaging in six. All patients
      presented with a slow-growing painless calf mass. All gave a history of major
      trauma to the lower leg many years before, but in only two cases did the
      referring clinician query whether trauma might be a contributory factor.
      Radiographs showed well-defined fusiform mineralised masses up to 25 cm in length
      arising within the calf. The calcification was consistently peripheral and plaque
      like. Ossification was not present. MR imaging showed the anterior compartment to
      be involved in four cases and all compartments in two. T1- and T2-weighted images
      showed peripheral low signal intensity, more prominent on the T2-weighted images,
      because of the peripheral mineralization. The contents of the masses were
      variable on T1-weighted images depending on the differing amounts of blood
      breakdown products and were heterogeneous on T2-weighted images. The latter may
      be explained by a combination of the mineralisation and T2 shortening due to
      blood breakdown products. A gadolinium chelate, administered in two cases, failed
      to show any appreciable enhancement. Calcific myonecrosis has characteristic
      clinical, radiographic and MR features that should make the condition easy to
      recognise. Despite its rarity, it should be included in the differential
      diagnosis of focal mineralisation of the calf.

PMID- 15480698
TI  - [Listeria endophthalmitis].
AB  - Listeria monocytogenes is a rare cause of endogenous endophthalmitis. During the
      last 20 years about 30 cases have been published, all of which showed similar
      clinical features and a profound visual loss mainly owing to delayed diagnosis.
      This case report is about an otherwise healthy 41-year-old woman whose diagnosis
      was established 17 days after the onset of symptoms by microbiological cultures.
      Under sufficient therapy signs of local inflammation disappeared and intraocular
      pressure decreased. Pars plana vitrectomy was necessary; although post-surgery
      complications developed, the result was complete recovery of visual acuity.

PMID- 15480699
TI  - [Photodynamic therapy in AMD. Strategy for indication].
AB  - In recent years several prospective studies have dealt with the therapeutic
      possibilities of PDT. In consideration of lesion size and its composition, a
      subtly differentiated scheme of therapy has been developed. Based on essential
      studies, recommendations on the indication for photodynamic therapy are
      summarized. They are complemented by references to safety and efficacy of
      photodynamic therapy. Users of PDT are given a short summary of relevant studies
      with current recommendations, which might ease the daily procedure of indicating
      photodynamic therapy.

PMID- 15480700
TI  - [Blepharitis].
AB  - Blepharitis is characterized by a great variety of clinical manifestations, which
      often include alterations of the ocular surface. This as well as its tendency to
      be therapy-resistant and recurrent explains why blepharitis marks a challenge for
      all ophthalmologists. Occasionally dermatologic diseases represent one of the
      causes of the disease, thus calling for an interdisciplinary approach. The
      present article describes the state of the art with regard to pathogenesis and
      therapy of blepharitis.

PMID- 15480701
TI  - [LASIK using a scanning spot excimer laser for the treatment of myopia and myopic
      astigmatism 3-Jahresergebnisse].
AB  - PURPOSE: The correction of refractive errors using laser in situ keratomileusis
      (LASIK) has become the primary refractive procedure worldwide. The purpose of
      this study was to evaluate LASIK within a retrospective cohort. PATIENTS AND
      METHODS: The mean preoperative spherical equivalent for the 34 consecutively
      treated eyes was -6.67+/-2.69 D. The LASIK operations were performed by a
      Hansatome microkeratome (Bausch and Lomb) and a scanning spot excimer laser
      (Technolas Keracor 217, Bausch and Lomb). For pre- and postoperative analysis the
      Datagraph med software (Version 2.7) was used. RESULTS: None of the treated eyes
      lost 2 or more lines of best-corrected visual acuity (BCVA). At the 36-month
      examination the spherical equivalent had changed to -0.47 D (mean increase of
      myopia: 0.13 D). No long-term complications were found in the study period.
      CONCLUSION: LASIK with superior hinge and scanning spot excimer ablation is an
      effective treatment for the correction of myopia and myopic astigmatism in the
      refractive range described above.

PMID- 15480703
TI  - Duration discrimination in the mouse (Mus musculus).
AB  - Detection thresholds for an increment in duration of a 10-kHz pure tone were
      determined in the NMRI mouse using a Go/NoGo-procedure and the method of constant
      stimuli. Thresholds for reference durations of 50, 100 and 200 ms were obtained
      presenting the signals at a fixed level or at a level varying by +/-3 dB.
      Thresholds were determined using signal-detection theory ( d'=1.0 or d'=1.8) and
      the criterion of 50% correct responses. For a fixed level, the average Weber
      fraction Delta T/ T (criterion of d'=1.8) significantly decreased from 1.18 or
      1.23 at reference durations of 50 or 100 ms, respectively, to 0.97 at a reference
      duration of 200 ms. Thresholds were on average reduced by 46.8 or 55.4% for the
      threshold criteria d'=1 or 50% correct responses, respectively. There was no
      effect of randomizing the level on the discrimination threshold. Duration
      discrimination in the NMRI mouse does not follow Weber's law. The results are
      consistent with a mechanism summing up neural impulses over the duration of the
      stimulus. The psychoacoustic data are compared with results obtained by Brand et
      al. (J Acoust Soc Am 51:1291-1223, 2000) on the representation of acoustic signal
      duration in the mouse inferior colliculus.

PMID- 15480704
TI  - AM representation in green treefrog auditory nerve fibers: neuroethological
      implications for pattern recognition and sound localization.
AB  - In addition to spectral call components, temporal patterns in the advertisement
      call envelope of green treefrog males ( Hyla cinerea) provide important cues for
      female mate choice. Rapid amplitude modulation (AM) with rates of 250-300 Hz is
      typical for this species' advertisement calls. Here we report data on the
      encoding of these rapid call modulations by studying the responses of single
      auditory nerve fibers to two-tone stimuli with envelope periodicities close to
      those of the natural call. The free-field response properties of 86 nerve fibers
      were studied from 32 anesthetized males. The accuracy of stimulus envelope coding
      was quantified using both a Gaussian function fit to the interspike interval
      histograms derived from the first seven 20-ms stimulus segments, and the vector
      strength metric applied to the phase-locked responses. Often, AM encoding in the
      initial stimulus segment was more faithful than that in its second half. This
      result may explain why conspecific females prefer calls in which the initial
      segment is unmasked rather than masked. Both the questions of pattern recognition
      and localization are discussed, and the data are related to behavioral
      observations of female choice and localization performance in this species.

PMID- 15480706
TI  - Acquired rectal fistula in human immunodeficiency virus-positive children: a
      causal or casual relationship?
AB  - Acquired rectal fistula in human immunodeficiency virus (HIV)-positive children
      is a new and worrisome entity. The aim of this paper is to highlight the
      relationship between HIV infection and acquired rectal fistula (RF) in children
      in order to create awareness among clinicians who attend to children. Over a 1
      year period, 11 girls aged 4 weeks-11 months (median 5 months) with acquired RF
      were managed at our institution. Ten were HIV-positive by enzyme-linked
      immunosorbent assay and confirmed by Western blot test. One child defaulted
      before the test. All the mothers and three fathers of the 10 children were
      seropositive for HIV. Bronchopneumonia, otitis media, oral thrush, diarrhoea, and
      lymphadenopathy were common associations. Treatment was essentially conservative
      because the result of surgical intervention was disappointing. Two of the infants
      and one of the fathers are now dead from full-blown acquired immunodeficiency
      syndrome. Acquired RF seems to be a sign of HIV infection in children. It will be
      necessary to screen any child presenting with acquired RF for HIV infection.

PMID- 15480705
TI  - Initial experience with antibiotic-impregnated silicone catheters for shunting of
      cerebrospinal fluid in children.
AB  - INTRODUCTION: Infection is a major complication of cerebrospinal fluid (CSF)
      shunting procedures. Recently, rifampin-impregnated and clindamycin-impregnated
      silicone catheters have been developed in an attempt to prevent and/or reduce the
      incidence of shunt infections. In vitro and in vivo animal studies have shown
      their efficacy in reducing bacterial colonization of catheters. However, these
      shunts are yet to be evaluated in clinical trials and their safety and efficacy
      in preventing shunt infections is unknown. METHODS: Between April 2002 and April
      2003, 31 children (age range 6 months to 17 years, mean 4.5 years) underwent
      implantation of an antibiotic-impregnated silicone catheter for CSF diversion.
      All surgeries were performed by a single neurosurgeon (HSM) at a single medical
      center. The Codman Hakim Bactiseal silicone catheter was used in all children.
      Thirty-two catheters were implanted in 31 children. All children have been
      followed since surgery (for an average of 19 months). For comparison, the
      previous 46 standard implanted shunts over a similar period of time were reviewed
      (average follow-up 31 months). RESULTS: Of the 32 implanted catheters, 11
      involved placement of a new complete shunt system, 8 were distal revisions, and
      13 were proximal/ventricular revisions. There were fewer early and late
      complications than in the standard shunt group (12.5 and 18.8% vs. 23.9 and
      34.8%). There was no local reaction from implantation of the catheters. One child
      contaminated his distal catheter by disrupting his abdominal incision. None of
      the other patients have developed any evidence of shunt infection to date.
      CONCLUSION: Rifampin-impregnated and clindamycin-impregnated silicone catheters
      appear to be safe and well tolerated in children. Preliminary results suggest a
      low incidence of shunt infection. Longer follow-up and a larger number of
      patients are needed to more accurately assess the efficacy of these catheters
      compared with traditional silicone catheters.

PMID- 15480707
TI  - Minimum postoperative antibiotic duration in advanced appendicitis in children: a
      review.
AB  - The suitable duration of antibiotic use following appendectomy for advanced
      appendicitis in children is still debated. A systematic review was performed,
      including published experimental and observational data of antibiotic use in
      children who had undergone appendectomy for advanced appendicitis. Data were
      extracted and analyzed according to predefined criteria. Twenty-eight studies
      were selected that included 2,284 patients. There was no consistency among the
      protocols regarding length of antibiotic use, discharge criteria, or use of home
      antibiotics following discharge. Limiting duration of antibiotic use to 3 days
      did not appear to be associated with higher rates of intraabdominal abscess or
      wound infection. In the absence of higher-level evidence, shortening of
      antibiotic regimens following surgery for pediatric complicated appendicitis
      appears to be safe.

PMID- 15480708
TI  - Thoracoscopic diaphragmatic procedures under artificial pneumothorax.
AB  - Diaphragmatic plication is technically simple using a conventional operative
      technique, but it requires a large skin incision and rib injury. We present an
      alternative technique for thoracoscopic plication of the diaphragm and evaluate
      the advantages of the procedure. Six patients (five with diaphragmatic
      eventration and one with diaphragmatic hernia with a sac) ranging in age from 8
      to 20 months were treated by this method. Three of the six cases were right
      sided, and three were left-sided. The operation was performed under artificial
      pneumothorax using carbon dioxide gas at 4 mmHg. Three trocars for laparoscopy
      were inserted at the 4th and 5th intercostal spaces. An adequate operative view
      was obtained by pressing the diaphragm throughout the operation. The eventrated
      diaphragm was plicated with several rows of nonabsorbable sutures in the
      anterolateral-to-posterolateral direction to prevent injury to the main phrenic
      nerve. A tight diaphragm was confirmed by decompressing the artificial
      pneumothorax. The technique was successfully performed in all cases, and the
      patients' postoperative courses were uneventful. During the operation, the
      hemodynamic effects of carbon dioxide gas at 4 mmHg were minimal. Over a mean
      follow-up period of 3.1 years (range, 1-6 years), no recurrence of diaphragmatic
      eventration was seen. Judging from the satisfactory postoperative course, this
      procedure is suitable for children with all forms of diaphragmatic eventration.

PMID- 15480709
TI  - Duodenogastric reflux following biliary reconstruction after excision of
      choledochal cyst.
AB  - Duodenogastric reflux (DGR) was assessed in patients surgically treated for
      choledochal cyst, with emphasis on two different biliary reconstruction methods:
      Roux-en-Y hepaticojejunostomy (HJ) and hepaticoduodenostomy (HD). Gastric bile
      monitoring with the Bilitec device revealed excessive DGR in patients in the HD
      group. Endoscopic findings demonstrated mild to moderate gastric mucosal erosion
      in patients after HD. In contrast, neither DGR nor gastritis was found in
      patients after HJ. This preliminary study suggests that HJ, rather than HD,
      should be recommended as a method of biliary reconstruction for pediatric
      patients with choledochal cyst. Careful observation of DGR should be continued in
      patients who have undergone HD.

PMID- 15480710
TI  - Ileocecal breast carcinoma metastasis.

PMID- 15480711
TI  - Perivascular clustering in temporal lobe epilepsy: oligodendroglial cells of
      unknown function.
AB  - Marked perivascular clustering (PC), i.e., groups and rows of small round cells
      along white matter vessels, is seen in temporal lobe epilepsy (TLE) specimens
      obtained by surgery. This study focuses on the constituting cell types and
      discusses clinical significance and pathogenesis of PC, which are so far unknown.
      Based on a series of 59 nonlesional TLE surgical specimens, we characterized PC
      by immunohistochemistry and correlated the amount of PC with clinical parameters.
      PC cells were variably positive for galactocerebroside, myelin basic protein and
      S-100 protein, while glial fibrillary acidic protein, vimentin, nestin and
      neuronal antigens were not expressed. There was no correlation between the amount
      of PC and any clinical feature, including age at surgery, age at epilepsy onset,
      duration of epilepsy, preoperative seizure frequency, childhood febrile
      convulsions, family history of epilepsy, and postsurgical outcome. Our findings
      suggest oligodendroglial differentiation of PC, while its primary (dysplastic)
      versus secondary (reactive) pathogenesis remains unresolved.

PMID- 15480712
TI  - Productive infection in the murine central nervous system with avian influenza
      virus A (H5N1) after intranasal inoculation.
AB  - The H5N1 type of influenza A virus isolated from human patients in 1997 has a
      characteristic hemagglutinin and was considered to be directly transmitted from
      birds. Although neuropathogenicity of this virus was not demonstrated in human
      autopsy cases, some experimental studies using mice have disclosed that this
      virus infects the central nervous system (CNS) after intranasal inoculation. In
      this study we focused on the topographical localization of virus-infected cells
      in the murine CNS after intranasal inoculation. We immunohistochemically examined
      virus-infected cells in mouse tissues using a rabbit antiserum recognizing the
      nucleoprotein of influenza A virus. The virus-infected cells appeared initially
      in the respiratory tract. Thereafter, the virus antigen-positive cells appeared
      in the olfactory system and the cranial nerve nuclei innervating the facial
      region. This suggests that this virus is principally transmitted from the nasal
      cavity to CNS through the cranial nerves. Neurons were frequently infected and
      glial and ependymal cells were also infected. Transneuronal transmission of the
      virus might play the important role of viral spread within the CNS.

PMID- 15480713
TI  - Arthrofibrosis following ACL reconstruction--reasons and outcome.
AB  - INTRODUCTION: Arthrofibrosis is a complication that severely influences the
      clinical outcome after anterior cruciate ligament (ACL) reconstruction. This
      retrospective clinical study analyses risk factors and outcome after arthrolysis
      in a large population. MATERIAL AND METHODS: Two hundred twenty-three patients
      who had undergone arthrolysis after ACL reconstruction were examined. Range of
      motion (ROM) was reduced due to arthrofibrosis of the joint in 70% (n=156). Other
      reasons, such as cyclops syndrome or osteoarthritis were found in 30% (n=67). The
      mean time interval between arthrolysis and follow-up was 4.29 years. We recorded
      timing of surgery, additional injuries, state of the knee before reconstruction,
      range of motion, pain during rehabilitation, beginning, duration and type of
      rehabilitation, severity and etiology of joint stiffness and the time between ACL
      reconstruction and revision. The present state of the knee was documented using
      the IKDC form. RESULTS: A significant correlation of arthrofibrosis and
      preoperative irritation (p<0.001), preoperative limited ROM (p=0.001),
      perioperative pain (p=0.046) and early beginning of muscle training (p=0.064) was
      found. Combination of a remaining loss of extension and development of
      degenerative joint disease was also significant (p=0.001). The decrease of sports
      activity compared with the level before ACL injury was highly significant
      (p<0.001). The criteria to minimize the risk of arthrofibrosis and the optimal
      timing of arthrolysis are pointed out.

PMID- 15480714
TI  - The German version of the Oxford Shoulder Score--cross-cultural adaptation and
      validation.
AB  - INTRODUCTION: The evaluation of health-related quality of life is an established
      criterion for the evaluation of therapeutic measurement. Especially in the
      English language, a great number of different questionnaires have been developed.
      The original, English-language 12-item Oxford shoulder score (OSS) is a recently
      developed and validated patient-completed outcome measure specifically designed
      for the evaluation of patients suffering from shoulder pathology other than
      instability. Because of the lack of a comparable instrument in German, this
      questionnaire was translated into German and subsequently tested for validity and
      reliability in a cross-sectional study. MATERIAL AND METHODS: Translation of the
      OSS was done according to the guidelines in the literature. One hundred two
      patients completed the German version of the OSS and the SF-36. Additionally, the
      Constant shoulder score and the UCLA shoulder score were included into the
      validation process. The psychometric properties feasibility and patient-burden
      parameters were also tested. RESULTS: The patients completed all questionnaires.
      The mean time required for completing the OSS was 3 min, 25 s; the mean time
      required for evaluation of the questionnaire was 35 s. The internal consistency
      tested by the Cronbach's alpha (0.94) was high. The reproducibility tested by two
      different methods showed no significant difference. The construct validity showed
      a significant correlation between the OSS and the other scores. CONCLUSION: The
      instrument proved to be valid by demonstrating the same correlations predicted by
      standard clinical assessments and a generic patient-based instrument. Application
      and evaluation in clinical trial proved feasible and minimally time consuming.
      Therefore, the German translation of the Oxford shoulder score is a valid and
      reliable tool, applicable to outcome studies on shoulder patients.

PMID- 15480715
TI  - Management of a traumatically avulsed skin-flap on the dorsum of the foot.
AB  - BACKGROUND: It is common for traumatologists to see avulsion injuries with
      resulting composite skin flaps. Simply reattaching the avulsed flap by suturing
      it back into its bed may result in ischemic necrosis of the distal portion of the
      flap. CASE REPORT: The authors present a case in which an extensive avulsion
      injury of the dorsum of the foot with amputation of the fourth and fifth toe was
      treated by defatting the avulsed flap and reattachment as a full-thickness graft.
      Healing was uneventful and no skin necrosis was encountered. At 1-year follow-up
      there was a stable skin situation at the dorsum of the foot. The patient has no
      difficulties with wearing shoes. However, there is diminished sensibility.
      CONCLUSIONS: Indications for this type of surgical technique include all types of
      avulsion or degloving injuries that create composite skin flaps prone to undergo
      ischemic necrosis if simply reattached. This quick and easy method should be in
      the armamentarium of each surgeon possibly dealing with this type of injury.

PMID- 15480716
TI  - Iatrogenic medial dislocation of hallucal sesamoids with hallux varus in an
      adolescent.
AB  - BACKGROUND: Iatrogenic hallux varus is a rare deformity linked to bunion surgery
      at late adult age. Here reported is the first adolescent case of acquired hallux
      varus and medial dislocation of both sesamoid bones. CASE REPORT: The patient had
      had a surgical intervention under his first metatarsophalangeal joint when he was
      10 years old. Correction of the deformity with a tendon transfer and medial
      capsular release alone-as was recommended for adults-was impossible in this
      adolescent, 8 years after the index surgery. Excision of the contracted medial
      structures and repair of the lateral retinaculum of the fibular sesamoid obtained
      a perfect correction of the dislocated sesamoid bones.

PMID- 15480717
TI  - Effect of high tibial flexion osteotomy on cartilage pressure and joint
      kinematics: a biomechanical study in human cadaveric knees. Winner of the AGA
      DonJoy Award 2004.
AB  - INTRODUCTION: Valgus high tibial osteotomy is an established treatment for
      unicompartmental varus osteoarthritis. However, only little is known about the
      effect of osteotomy in the sagittal plane on biomechanical parameters such as
      cartilage pressure and joint kinematics. This study investigated the effects of
      high tibial flexion osteotomy in a human cadaver model. MATERIALS AND METHODS:
      Seven fresh human cadaveric knees underwent an opening wedge osteotomy of the
      proximal tibia in the sagittal plane. The osteotomy was opened anteriorly, and
      the tibial slope of the specimen was increased gradually. An isokinetic flexion
      extension motion was simulated in a kinematic knee simulator. The contact
      pressure and topographic pressure distribution in the medial joint space was
      recorded using an electronic pressure-sensitive film. Simultaneously the motion
      of the tibial plateau was analyzed three-dimensionally by an ultrasonic tracking
      system. The traction force to the quadriceps tendon which was applied by the
      simulator for extension of the joint was continuously measured. The experiments
      were carried out with intact ligaments and then after successively cutting the
      posterior and anterior cruciate ligaments. RESULTS: The results demonstrate that
      tibial flexion osteotomy leads to a significant alteration in pressure
      distribution on the tibial plateau. The tibiofemoral contact area and contact
      pressure was shifted anteriorly, which led to decompression of the posterior half
      of the plateau. Moreover, the increase in the slope resulted in a significant
      anterior and superior translation of the tibial plateau with respect to the
      femoral condyles. Posterior subluxation of the tibial head after cutting the
      posterior cruciate ligament was completely neutralized by the osteotomy. The
      increase in slope resulted in a significant higher quadriceps strength which was
      necessary for full knee extension. CONCLUSIONS: We conclude from these results
      that changes in tibial slope have a strong effect on cartilage pressure and
      kinematics of the knee. Therapeutically a flexion osteotomy may be used for
      decompression of the degenerated cartilage in the posterior part of the plateau,
      for example, after arthroscopic partial posterior meniscectomy. If a valgus
      osteotomy is combined with a flexion component of the proximal tibia, complex
      knee pathologies consisting of posteromedial cartilage damage and posterior and
      posterolateral instability can be addressed in one procedure, which facilitates a
      quicker rehabilitation of these patients.

PMID- 15480718
TI  - Determination of the antioxidant capacity of an antioxidant combination using the
      fluoroscan assay in vitro and visualization of its effects using histological
      methods.
AB  - The effects of a well-defined combination of antioxidants on oxidative stress
      were investigated in vitro using classical techniques together and its protective
      effects against UV damage were investigated using a newly developed skin model.
      After determining the cytotoxic potential of the combination, its quenching
      effect on the oxidative stress induced by hydrogen peroxide was quantified by a
      nonfluorescent (C-H2DCF-DA/AM)/fluorescent (C-DCF) dye system using the
      fluoroscan assay. Two different skin models consisting of normal human skin
      fibroblasts and the keratinocyte cell line HaCaT were developed and subsequently
      used to visualize the protective effects of the combination against UVA damage.
      No evidence of any cytotoxic potential of the combination could be seen.
      Supplementation of human skin fibroblasts demonstrated a clear, dose-dependent
      enhancement of the antioxidative capacity of these cells. Histological findings
      confirmed the beneficial effects of the antioxidants present in the combination
      in the skin models used. Supplementation induced morphological changes leading to
      a thicker epidermal layer providing evidence of the positive effects of the
      treatment on the viability of the keratinocytes after UVA irradiation. This in
      vitro study provided convincing evidence of the combined antioxidative action of
      alpha-tocopherol, beta-carotene, tomato extract, grape seed extract, ascorbic
      acid and selenium yeast, and indicated a potential beneficial action of the
      combination against oxidative stress caused by external oxidative stress factors
      such as UV irradiation.

PMID- 15480720
TI  - Vaginal administration of oral micronized estradiol results in successful twin
      pregnancy in a functionally agonadal woman.
AB  - CASE REPORT: A 31-year-old nulligravid woman seeking fertility treatment with in
      vitro fertilization and intracytoplasmic sperm injection failed to achieve
      pregnancy. Supernumerary embryos were cryopreserved for future use. In
      preparation for the transfer of the frozen embryos, the patient was prescribed
      hormones, which included pituitary down-regulation with leuprolide acetate,
      followed by oral micronized estradiol (E2) and vaginal progesterone (P4)
      suppositories. At the time of embryo transfer (ET) it was noted that the patient
      had misunderstood her instructions and was administering both her estrogen and
      progesterone vaginally. Ultrasound examination revealed a well-developed
      endometrium adequate for ET so the procedure was performed, and at that point she
      was instructed to use E2 orally as originally prescribed. Two weeks later, her
      beta-hCG was elevated, and subsequent ultrasound examinations revealed a twin
      gestation. The pregnancy progressed normally. CONCLUSION: This patient's hormones
      were adequately replaced despite vaginal placement of oral medication. Although
      not commonly prescribed, oral E2 tablets may be administered vaginally in
      functionally agonadal women preparing for ET, and may serve as an alternative
      route for women who experience difficulties with oral formulations.

PMID- 15480721
TI  - Serum calcium and serum magnesium in normal and preeclamptic pregnancy.
AB  - OBJECTIVE: The aims of this study were to measure serum levels of calcium and
      magnesium in preeclamptic pregnancies and to compare them with those in normal
      pregnancies. MATERIALS AND METHODS: We collected venous serum samples from 40
      preeclamptic pregnant women and 40 normal pregnant women. The blood samples were
      analyzed for calcium and magnesium, using a colorimetric analyzer. The data were
      analyzed using the Student's t-test, chi2-test or Fisher exact tests when
      appropriate. RESULTS: The serum calcium concentration in preeclamptic pregnant
      women is significantly lower than that in normal pregnant women (9.0 +/- 0.4
      mg/dl vs. 9.7 +/- 0.7 mg/dl, p < 0.0001). Like serum calcium, serum magnesium
      concentration in preeclamptic women is significantly lower than that in normal
      pregnant women (0.77 +/- 0.08 mmol/l vs. 0.85 +/- 0.09 mmol/l, p = 0.001).
      CONCLUSION: This study shows that both serum calcium and serum magnesium levels
      in preeclamptic pregnant women are lower than in normal pregnant women. These
      findings support the hypothesis that hypocalcemia and hypomagnesemia are possible
      etiologies of preeclampsia.

PMID- 15480722
TI  - The feasibility and morbidity of distal pancreatectomy in extensive cytoreductive
      surgery for advanced epithelial ovarian cancer.
AB  - INTRODUCTION: Pancreatic metastasis of ovarian cancer is extremely rare and its
      therapeutic approach is not well documented. The objective of this study is to
      evaluate the feasibility and morbidity of pancreatic resection as a component of
      extensive cytoreductive surgery in epithelial ovarian cancer (EOC) patients with
      pancreas metastasis. METHODS: Between December 2000 and February 2003, 98 EOC
      patients were treated with primary cytoreduction. Six (6.12%) of these patients
      had pancreatic tail metastasis and were operated on using the distal
      pancreatectomy. RESULTS: Preoperatively, only 1 (16.7%) of the 6 patients had
      signs of metastasis to the pancreas on computed tomography (CT). Optimal
      cytoreduction (absent or < or =1 cm macroscopic residual tumor size) was achieved
      in all patients. In the early postoperative period, there were 4 patients (66.7%)
      with complications and no perioperative mortality. In 1 patient (16.7%), glucose
      intolerance as a late complication of pancreatic resection was detected. All
      patients received six cycles of platinum-based adjuvant chemotherapy following a
      cytoreductive operation. Mean follow-up was 27 months (range 9-36), and 3 (50%)
      patients are still alive at the end of the study period. The two-year survival
      rate was 66.7%. CONCLUSION: In conclusion, if optimal cytoreduction is foreseen
      in advanced epithelial ovarian cancer with pancreatic tail metastasis, distal
      pancreatectomy should be kept in mind. This procedure has acceptable morbidity
      and seems to be an attribute for survival.

PMID- 15480724
TI  - 6th Three-Country Symposium for Biological Psychiatry. 21-24 October 2004, Bern,
      Switzerland. Abstracts.

PMID- 15480723
TI  - Magnetic resonance imaging in Posterior Reversible Encephalopathy Syndrome:
      report of three cases and review of literature.
AB  - INTRODUCTION: Eclampsia is one of the main causes of Posterior Reversible
      Encephalopathy Syndrome (PRES) a recent clinico-neuroradiological entity
      represented by characteristic MR findings of a symmetric bilateral
      subcortical/cortical hyperintensity in T2-weighted images, more often in parieto
      occipital lobes, accompanied by clinical neurological alterations.
      Neuroradiological and clinical alterations are commonly completely reversible
      although ischemic evolution has been described. The pathophysiology is still a
      matter of debate. Specific magnetic resonance (MR) techniques, such as FLAIR
      (fluid attenuated inversion recovery) and DWI (diffusion weighted images)
      sequences, have improved the ability to detect subcortical/cortical lesions and
      helped to clarify the underlying pathophysiological mechanism of cerebrovascular
      involvement, which results important for an appropriate therapeutic decision.
      CASE REPORT AND DISCUSSION: We report the MR imaging findings of three patients
      with eclampsia and PRES as well as a careful review of literature.

PMID- 15480725
TI  - Chromosome territory arrangement and homologous pairing in nuclei of Arabidopsis
      thaliana are predominantly random except for NOR-bearing chromosomes.
AB  - Differential painting of all five chromosome pairs of Arabidopsis thaliana
      revealed for the first time the interphase chromosome arrangement in a euploid
      plant. Side-by-side arrangement of heterologous chromosome territories and
      homologous association of chromosomes 1, 3 and 5 (on average in 35-50% of nuclei)
      are in accordance with the random frequency predicted by computer simulations.
      Only the nucleolus organizing region (NOR)-bearing chromosome 2 and 4 homologs
      associate more often than randomly, since NORs mostly attach to a single
      nucleolus. Somatic pairing of homologous approximately 100 kb segments occurs
      less frequently than homolog association, not significantly more often than
      expected at random and not simultaneously along the homologs. Thus, chromosome
      arrangement in Arabidopsis differs from that in Drosophila (characterized by
      somatic pairing of homologs), in spite of similar genome size, sequence
      organization and chromosome number. Nevertheless, in up to 31.5% of investigated
      Arabidopsis nuclei allelic sequences may share positions close enough for
      homologous recombination.

PMID- 15480726
TI  - Satellite repeats in the functional centromere and pericentromeric
      heterochromatin of Medicago truncatula.
AB  - Most eukaryotic centromeres contain long arrays of tandem repeats, with unit
      lengths of 150-300 bp. We searched for such repeats in the functional centromeres
      of the model legume Medicago truncatula (Medicago) accession Jemalong A17. To
      this end three repeats, MtR1, MtR2 and MtR3, were identified in 20 Mb of a low
      pass, whole genome sequencing data set generated by a random shotgun approach.
      The nucleotide sequence composition, genomic organization and abundance of these
      repeats were characterized. Fluorescent in situ hybridization of these repeats on
      chromosomes at meiosis I showed that only the MtR3 repeat, encompassing stretches
      of 450 kb to more than 1.0 Mb, is located in the functional portion of all eight
      centromeres. MtR1 and MtR2 occupy distinct regions in pericentromeric
      heterochromatin. We also studied the presence and distribution of MtRs in
      Medicago accession R108-1, a genotype with a genome that is 20% smaller than that
      of Jemalong A17. We determined that while MtR3 is also centromeric on all
      pachytene bivalents in R108-1, MtR1 and MtR2 are not present in the R108 genome.

PMID- 15480728
TI  - Systematic gene targeting on the X chromosome of Drosophila melanogaster.
AB  - The genome of the model organism Drosophila melanogaster has been sequenced and
      annotated. Based on this groundwork, we performed a systematic genetic screen of
      the D. melanogaster X chromosome, which carries about one sixth of the genes of
      the organism. We generated a collection of single P-element insertions to provide
      genetic and molecular access to virtually all X-chromosomal genes. The study
      complements earlier work designed to systematically identify vital genes on the X
      chromosome by targeting transcription units which are phenotypically silent. We
      describe single UAS sequence-bearing P-element insertions throughout the X
      chromosome, which allows one to express the tagged genes under control of
      tissue/organ-directed GAL4 activity. In addition, the present collection of
      single insertion lines provides a tool to generate chromosomal deletions which
      are on average less than 33 kb in size.

PMID- 15480727
TI  - Conspicuous accumulation of transcription elongation repressor hrp130/CA150 on
      the intron-rich Balbiani ring 3 gene.
AB  - Chromosomal puffs on the polytene chromosomes in the dipteran Chironomus tentans
      offer the possibility of comparing the appearance of RNA-binding proteins at
      different transcription sites. We raised a monoclonal antibody that recognized a
      130 kDa protein, designated hrp130. Immunocytological analysis of isolated
      chromosomes showed that hrp130 is heavily accumulated in a specific puff, called
      Balbiani ring 3; only occasionally is hrp130 abundant in one or two additional
      puffs on other chromosomes. The immunolabeling was sensitive to RNase treatment,
      suggesting that hrp130 is associated with nascent ribonucleoproteins. As shown by
      immunoelectron microscopy hrp130 is distributed along the active BR3 genes. The
      full sequence of hrp130 was determined by cDNA cloning. The protein comprises
      1028 amino acids and contains three WW domains in the N-terminal half and six FF
      domains in the C-terminal half of the molecule. The protein is conserved from
      Caenorhabditis elegans to mammals; the human homolog is known as the
      transcription elongation repressor CA150. We propose that the abundance of
      hrp130/CA150 in BR3 is connected with the exceptionally high level of splicing in
      this locus and that hrp130/CA150 adjusts the transcription rate to the numerous
      splicing events taking place along the gene to ensure proper splicing.

PMID- 15480729
TI  - Evolution and arrangement of the hsp70 gene cluster in two closely related
      species of the virilis group of Drosophila.
AB  - To investigate the genetic basis of differing thermotolerance in the closely
      related species Drosophila virilis and Drosophila lummei, which replace one
      another along a latitudinal cline, we characterized the hsp70 gene cluster in
      multiple strains of both species. In both species, all hsp70 copies cluster in a
      single chromosomal locus, 29C1, and each cluster includes two hsp70 genes
      arranged as an inverted pair, the ancestral condition. The total number of hsp70
      copies is maximally seven in the more thermotolerant D. virilis and five in the
      less tolerant D. lummei, with some strains of each species exhibiting lower copy
      numbers. Thus, maximum hsp70 copy number corresponds to hsp70 mRNA and Hsp70
      protein levels reported previously and the size of heat-induced puffs at 29C1.
      The nucleotide sequence and spacing of the hsp70 copies are consistent with
      tandem duplication of the hsp70 genes in a common ancestor of D. virilis and D.
      lummei followed by loss of hsp70 genes in D. lummei. These and other data for
      hsp70 in Drosophila suggest that evolutionary adaptation has repeatedly modified
      hsp70 copy number by several different genetic mechanisms.

PMID- 15480730
TI  - Cuts to the offender's own hand--unintentional self-infliction in the course of
      knife attacks.
AB  - In a knife attack the perpetrator can unintentionally injure his own hand, if the
      knife does not have an adequate handguard and the tip of the blade hits a solid,
      mostly bony structure while being violently thrust into the victim's body. The
      injuries occurring under these conditions are localized on the flexor side of the
      knife-holding hand and may include the index, middle, ring and little fingers.
      They are seen particularly often on the little finger at the level of the
      proximal phalanx and in the skin fold of the proximal interphalangeal joint. The
      majority of these cuts run transversely to the longitudinal axis of the fingers
      and can show a step-like arrangement with different distances to the
      metacarpophalangeal joints, often from ulnar-proximal to radial-distal. In the
      six cases presented the injuries were most pronounced on the ulnar side of the
      hand. When the flexor tendons of the fingers are also severed and the tendon
      stumps are strongly retracted this indicates that the fist was firmly closed at
      the time of the injury.

PMID- 15480731
TI  - Canine-specific STR typing of saliva traces on dog bite wounds.
AB  - Forensic investigations in dog attacks usually involve the examination of bite
      marks and toothprints, the dog's stomach and pathological methods. For
      identification of the offending dog we evaluated canine STR typing of saliva
      traces on dog bite marks. The specificity of 15 canine-specific STRs was tested
      on human-canine DNA mixtures prior to an applied study in which 52 cases of dog
      bites were investigated. The first-aid wound bandages as well as swab samples
      from the surrounding area of the wound were used for DNA analyses. Generally, it
      was possible to obtain a canine-specific STR profile from the dog's saliva left
      on the wound area, even when high background of human DNA was present (blood).
      Interestingly, we found canine STR typing to be more successful when the bandages
      and swabs showed high amounts of human blood, i.e. when the dog bite was severe.
      Canine saliva was then sometimes visible as white-coloured secretion on the human
      blood surface. Less severe bite cases, which did not result in bleeding wounds,
      showed less success in obtaining useful STR results, probably due to the fact
      that the surface of the wounds may have been treated before the victims consulted
      medical aid which therefore removed the canine cells.

PMID- 15480732
TI  - Temperature-based death time estimation with only partially known environmental
      conditions.
AB  - The temperature-oriented death time determination is based on mathematical model
      curves of postmortem rectal cooling. All mathematical models require knowledge of
      the environmental conditions. In medico-legal practice homicide is sometimes not
      immediately suspected at the death scene but afterwards during external
      examination of the body. The environmental temperature at the death scene remains
      unknown or can only be roughly reconstructed. In such cases the question arises
      whether it is possible to estimate the time since death from rectal temperature
      data alone recorded over a longer time span. The present study theoretically
      deduces formulae which are independent of the initial and environmental
      temperatures and thus proves that the information needed for death time
      estimation is contained in the rectal temperature data. Since the environmental
      temperature at the death scene may differ from that during the temperature
      recording, an additional factor has to be used. This is that the body core is
      thermally well isolated from the environment and that the rectal temperature
      decrease after a sudden change of environmental temperature will continue for
      some time at a rate similar to that before the sudden change. The present study
      further provides a curve-fitting procedure for such scenarios. The procedure was
      tested in rectal cooling data of from 35 corpses using the most commonly applied
      model of Henssge. In all cases the time of death was exactly known. After
      admission to the medico-legal institute the bodies were kept at a constant
      environmental temperature for 12-36 h and the rectal temperatures were recorded
      continuously. The curve-fitting procedure led to valid estimates of the time
      since death in all experiments despite the unknown environmental conditions
      before admission to the institute. The estimation bias was investigated
      statistically. The 95% confidence intervals amounted to +/-4 h, which seems
      reasonable compared to the 95% confidence intervals of the Henssge model with
      known environmental temperature. The presented method may be of use for
      determining the time since death even in cases in which the environmental
      temperature and rectal temperature at the death scene have unintentionally not
      been recorded.

PMID- 15480733
TI  - Hyperconvolution of the inner limiting membrane in vitreomaculopathies.
AB  - BACKGROUND: This study investigates the similarities and differences between
      epiretinal membranes in four clinically distinct types of vitreomaculopathy. We
      propose a hypothesis on the origin of the predominant cell type and its potential
      role in causing these conditions. METHODS: Epiretinal membranes (ERMs) surgically
      removed from a prospective, consecutive series of vitrectomies for macular pucker
      associated with an untreated peripheral horseshoe tear (MP), cellophane
      maculopathy (CM), stage 4 macular hole (MH) and vitreomacular traction syndrome
      (VMT) were examined by light microscopy and by immunocytochemistry (ICC) using
      antibodies marking type IV collagen, type II collagen, glial fibrillary acidic
      protein (GFAP), and low- and high-molecular-weight cytokeratin (MNF116). These
      specimens were compared with post-mortem control eyes with and without
      physiological posterior vitreous detachment (PVD). Light microscopy was carried
      out on 5-microm-thick sections cut from formalin-fixed, paraffin-embedded tissue
      blocks. Appropriate autoclave or enzyme pre-digestion steps were deployed to
      retrieve antigens for ICC. No patient had undergone previous vitreoretinal
      surgery or peripheral retinopexy. RESULTS: From a series of 38 patients, (13 CM,
      8 MP, 16 MH and 1 VMT) a total of 20 specimens contained sufficient tissue for
      histology and immunocytochemistry. All specimens contained portions of inner
      limiting membrane (ILM) coated by GFAP-positive cells. Specimens from patients
      with MP and CM exhibited hyperconvolution of the ILM, which was not found in the
      specimens from patients with MH or VMT or in the control eyes. Hyperconvolution
      was associated with increased glial cell density, GFAP staining intensity and
      duplication of ILM basement membrane. Three cases of ERMs from the MP group
      contained, in addition, cytokeratin-positive cells. In the control group; post
      mortem eyes with PVDs showed patchy staining of the posterior hyaloid membrane
      for GFAP and type 4 collagen. Post-mortem eyes with attached gel showed weak
      positivity of the ILM for type 4 collagen, and a monolayer of GFAP-positive cells
      lined the vitreous aspect of the ILM. CONCLUSIONS: These results indicate that
      glial cells are fundamentally important in the formation of ERMs found in this
      group of vitreomaculopathies. The hyperconvolution and duplication of the ILM in
      CM and MP were striking and distinctive features and suggest a mechanism by which
      these membranes exert tractional forces on the retina. Post-mortem control eyes
      contained a similar (but more dispersed) population of GFAP-positive cells in the
      region of the ILM, suggesting the primary aetiology for CM and MP may originate
      within the ILM. ERMs from MP cases may, in addition, contain cytokeratin-positive
      cells, of probable RPE origin.

PMID- 15480734
TI  - Reflections.

PMID- 15480735
TI  - Comparison of the small heat shock proteins alphaB-crystallin, MKBP, HSP25,
      HSP20, and cvHSP in heart and skeletal muscle.
AB  - Seven members of the small heat shock protein (sHSP) family are exceptional with
      respect to their constitutive high abundance in muscle tissue. It has been
      suggested that sHSPs displaying chaperone-like properties may stabilize
      myofibrillar proteins during stress conditions and prevent them from loss of
      function. In the present study five sHSPs (alphaB-crystallin, MKBP, HSP25, HSP20,
      and cvHSP) were investigated with respect to similarities and differences of
      their expression in heart and skeletal muscle under normal and ischemic
      conditions. In ischemic heart and skeletal muscle these five sHSPs translocated
      from cytosol to the Z-/I-area of myofibrils. Myofibrillar binding of all sHSPs
      was very tight and resisted for the most part extraction with 1 M NaSCN or 1 M
      urea. MKBP and HSP20 became extracted by 1 M NaSCN to a significant extent
      indicating that these two sHSPs may bind partially to actin-associated proteins
      which were completely extracted by this treatment. Ultrastructural localization
      of alphaB-crystallin showed diffuse distribution of immunogold label throughout
      the entire I-band in skeletal muscle fibers whereas in cardiomyocytes alphaB
      crystallin was preferentially located at the N-line position of the I-band. These
      observations indicate different myofibrillar binding sites of alphaB-crystallin
      in cardiomyocytes versus skeletal muscle fibers. Further differences of the
      properties of sHSPs could be observed regarding fiber type distribution of sHSPs.
      Thus sHSPs form a complex stress-response system in striated muscle tissue with
      some common as well as some distinct functions in different muscle types.

PMID- 15480736
TI  - Inhibin/activin subunits alpha, beta-A and beta-B are differentially expressed in
      normal human endometrium throughout the menstrual cycle.
AB  - Inhibins are dimeric glycoproteins composed of an alpha (alpha) subunit and one
      of two possible beta (beta-) subunits (betaA or betaB). The aims of this study
      were to assess the frequency and tissue distribution patterns of the inhibin
      subunits in normal human endometrium. Samples from human endometrium from
      proliferative phase (PP; n=32), early secretory phase (ES; n=10) and late
      secretory phase (LS; n=12) were obtained. Immunohistochemistry,
      immunofluorescence and a statistical analysis were performed. All three inhibin
      subunits were expressed by normal endometrium by immunohistochemistry and
      immunofluorescence. Inhibin-alpha was primarily detected in glandular epithelial
      cells, while inhibin-beta subunits were additionally localised in stromal tissue.
      Inhibin-alpha staining reaction increased significantly between PP and ES
      (P<0.05), PP and LS (P<0.01), and ES and LS (P<0.02). Inhibin-betaA and -betaB
      were significant higher in LS than PP (P<0.05) and LS than ES (P<0.05). All three
      inhibin subunits were expressed by human endometrium varying across the menstrual
      cycle. This suggests substantial functions in human implantation of inhibin-alpha
      subunit, while stromal expression of the beta subunits could be important in the
      paracrine signalling for adequate endometrial maturation. The distinct expression
      in human endometrial tissue suggests a synthesis of inhibins into the lumen and a
      predominant secretion of activins into the stroma.

PMID- 15480738
TI  - Expression of estrogen receptors in the efferent ductule of male sheep fetuses
      during gestation.
AB  - There is as yet no report about the developmental changes of estrogen receptors
      (ERs) in the male reproductive system of the sheep fetus. In the present study,
      the testis, efferent ductule, and epididymis of sheep fetuses were collected at
      days 70, 90, and 120 of gestation and in the newborn lamb. ER alpha (ERalpha) and
      ER beta (ERbeta) were detected by immunohistochemistry. The results showed that
      ERbeta staining was negative in all of the examined tissues throughout gestation,
      whereas ERalpha immunoreactivity was only located in the nuclei of the efferent
      ductule epithelium. In addition, both ERalpha staining intensity and the number
      of ERalpha-positive cells were higher at day 90 of gestation, compared with that
      at day 70 and at birth. These results suggest that estrogen may play important
      roles in efferent ductule development in sheep fetuses.

PMID- 15480737
TI  - Localization of endothelin receptors in bleomycin-induced pulmonary fibrosis in
      the rat.
AB  - Pulmonary fibrosis is characterized by excessive extracellular matrix deposition
      with concomitant loss of gas exchange units, and endothelin-1 (ET-1) has been
      implicated in its pathogenesis. Increased levels of ET-1 from tissues and
      bronchoalveolar lavage have been reported in patients with pulmonary fibrosis and
      in animal models after intratracheal bleomycin. We characterized the cellular
      distribution of alveolar ET receptors by immunohistochemistry in bleomycin
      induced pulmonary fibrosis in the rat and determined the regulation by bleomycin
      of ET receptor mRNA expression in isolated alveolar macrophages and rat lung
      fibroblasts. We found significant increases in the numbers of fibroblasts and
      macrophages at day 7 compared to day 28 and control animals. ET(B) receptor
      immunoreactivity was observed on fibroblasts and invading monocytes. Isolated
      fibroblasts expressed both ET(A) and ET(B) receptor mRNA, and ET(A) receptor mRNA
      was upregulated by bleomycin. Isolated resident alveolar macrophages expressed
      neither ET(A) nor ET(B) receptor mRNA which were also not induced by bleomycin.
      We conclude that, while ET(B) receptor stimulation of fibroblasts and monocytes
      recruited during bleomycin-induced lung injury exerts antagonistic effects on
      fibroblast collagen synthesis, the observed increase in the number of fibroblasts
      in vivo and upregulation of fibroblast ET(A) receptor mRNA by bleomycin in vitro
      point to a predominance of the profibrotic effects of ET receptor engagement.

PMID- 15480739
TI  - Sequence of IGF-I, IGF-II, and HGF expression in regenerating skeletal muscle.
AB  - Various cytokines are thought to play a role in muscle regeneration, however, the
      interaction and mechanisms of action of these cytokines remains largely unknown.
      In this study, we investigated the role of HGF, IGF-I, and IGF-II during
      myogenesis using the regeneration model of skeletal muscle as well as myoblast
      culture. RT-PCR analysis revealed that HGF and IGF-I expressions were markedly
      upregulated, in regenerating muscle. In contrast, there was no significant
      difference in IGF-II expression between normal and regenerating muscle.
      Immunohistochemical analysis demonstrated that HGF was expressed mostly by
      myocytes during the early stages of muscle regeneration. Additionally, HGF
      inhibited the formation of myotubes by myoblasts, but promoted cellular
      proliferation. Otherwise, IGF-I and IGF-II were expressed by myocytes through the
      early to middle stages of muscle regeneration. The addition of HGF to myoblast
      growing in vitro significantly increased the number of cells. These findings
      indicate that these three cytokines have pleiotropic effects in regenerating
      skeletal muscle.

PMID- 15480740
TI  - Acute and delayed neuromuscular adjustments of the triceps surae muscle group to
      exhaustive stretch-shortening cycle fatigue.
AB  - Stretch-shortening cycle (SSC)-type fatigue is associated with acute and delayed
      functional defects, and appears to be a useful model to reveal the flexibility of
      both central and reflex adjustments to the contractile failure. SSC fatigue was
      induced in an experimental (EXP) group (n=6) on a sledge ergometer with an
      exhaustive rebound exercise with submaximal effort. The acute (POST) and 2-day
      delayed (2D) neuromuscular changes with fatigue were examined in a short
      submaximal rebound task (REBOUND) and in a maximal isometric plantarflexion test
      (ISOM). The EXP group results were compared to those of a control group (n=6) who
      did not perform the exhaustive SSC exercise and did not present any change in the
      tests. In the EXP group, the ISOM test revealed mostly a large decrease in
      maximal plantarflexion force at 2D that was correlated with the reduced mean
      soleus muscle (SOL) activation. Indicating "task-dependent" fatigue effects on
      the neural changes, the REBOUND test revealed both acute and delayed increases in
      SOL activation. Supporting central neural changes, SOL preactivation increased in
      POST and 2D. The neural flexibility along time and across muscles was
      demonstrated by the shifted increase in SOL activation from the braking phase in
      POST to the push-off phase in 2D, and associated increased gastrocnemius medialis
      preactivation in 2D. In contrast, activation during the stretch-reflex period was
      constant in POST, and decreased in 2D. These results would support the influence
      of musculotendinous afferents on the flexible neural adjustments to the SSC
      induced contractile failure.

PMID- 15480742
TI  - Effect of exercise training on muscle glucose transporter 4 protein and
      intramuscular lipid content in elderly men with impaired glucose tolerance.
AB  - This study determined the effects of exercise training on adaptations of skeletal
      muscle including fibre composition, capillarity, intra-muscular triglyceride
      concentration (IMTG), as well as glucose transporter 4 protein (GLUT4) and
      metabolic enzyme activities. Percutaneous muscle biopsies from the vastus
      lateralis muscle were obtained from non-obese elderly Korean men (n = 10; age
      range 58-67 years) with impaired glucose tolerance. Subjects performed 12 weeks
      of endurance exercise training (60-70% of the heart rate reserve). The training
      program improved the total GLUT4 protein expression (P < 0.01), decreased the
      IMTG, increased the fatty acid oxidation capacity, and the number of capillaries
      around type 1 fibres (P < 0.05), whereas no significant alteration was observed
      around type II fibres. All data are presented as the means together with the
      standard deviation. The results suggest that endurance training evokes
      morphological and biochemical changes in the skeletal muscle of elderly men with
      impaired glucose tolerance that may be considered to limit the development of
      type 2 diabetes.

PMID- 15480741
TI  - Muscle tissue oxygenation, pressure, electrical, and mechanical responses during
      dynamic and static voluntary contractions.
AB  - Dynamic muscle contractions have been shown to cause greater energy turnover and
      fatigue than static contractions performed at a corresponding force level.
      Therefore, we hypothesized that: (1) electro- (EMG) and mechanomyography (MMG),
      intramuscular pressure (IMP), and reduction in muscle oxygen tension (rTO(2))
      would be larger during dynamic (DYN) than intermittent static (IST) low force
      contractions; and that (2) oxygen tension would remain lower in the resting
      periods subsequent to DYN as compared to those following IST. Eight subjects
      performed elbow flexions with identical time-tension products: (1) DYN as a 20
      degrees elbow movement of 2 s concentric and 2 s eccentric followed by a 4 s
      rest; and (2) IST with a 4 s contraction followed by a 4 s rest. Each session was
      performed for 1 min at 10 and 20% of the maximal voluntary contraction (MVC). The
      force, bipolar surface EMG, MMG, IMP, rTO(2) were measured simultaneously from
      the biceps brachii, and the data presented as the mean values together with the
      standard error of the means. Comparison of the corresponding time periods showed
      the EMG(rms) and MMG(rms) values to be larger during DYN than IST (concentric
      phase: DYN vs IST were 14.2 vs 9.4, and 22.0 vs 15.9%(max)-EMG(rms); eccentric
      phase: in DYN, the MMG was approximately 1.5 and approximately 2.0-fold IST at 10
      and 20%MVC, respectively). In contrast, the IMP of the concentric phase in DYN
      was lower than in IST (2.3 vs 29.5 and 10.9 vs 42.0 mmHg at 10 and 20%MVC,
      respectively), and a similar picture was seen for the eccentric phase. However,
      no differences were seen in rTO(2) in either the contraction or the rest periods.
      In a prolonged rest period (8 s) after the sessions, DYN but not IST showed
      rTO(2) above baseline level. In conclusion, rTO(2) in DYN and IST were similar in
      spite of major differences in the MMG and EMG responses of the muscle during
      contraction periods. This may relate to the surprisingly lower IMP in DYN than
      IST.

PMID- 15480743
TI  - A stochastic model for the detection of coherent motion.
AB  - A computational model is presented for the detection of coherent motion based on
      template matching and hidden Markov models. The premise of this approach is that
      the growth in detection sensitivity is greater for coherent motion of structured
      forms than for random coherent motion. In this preliminary study, a recent
      experiment was simulated with the model and the results are shown to be in
      agreement with the above premise. This model can be extended to be part of a more
      complex and elaborate computational visual system.

PMID- 15480744
TI  - Analysis of mechanical impedance in human arm movements using a virtual tennis
      system.
AB  - The dynamic characteristics of human upper extremities are usually expressed by
      mechanical impedance. Although many studies have discussed human impedance
      characteristics, there are no reports on control abilities of task-related
      impedance in skilled human hand movements. This paper proposes a virtual sports
      system using a virtual reality technique to examine human movements. The
      differences in movements between skilled and unskilled subjects are investigated
      through a series of experiments. Then, the human impedance of a skilled player is
      estimated and analyzed in the preliminary phase of motion.

PMID- 15480745
TI  - Retention of peptide hormones during partial secretion in pituitary somatotrophs
      and corticotrophs.
AB  - The secretion of peptide hormones during exocytosis of an individual vesicle can
      result in either complete discharge of vesicle content or can occur in a partial
      manner in which some hormone is retained during transient fusion. In anterior
      pituitary lactotrophs, the retained hormone prolactin was internalized and
      recycled into a pool of vesicles that underwent preferential use during
      subsequent exocytic stimulations [Bauer et al., (2004) J Cell Sci. 117:2193
      2202]. The aim of the present study was to determine whether retention and
      preferential recycling of retained hormones occurred in other anterior pituitary
      cells. Stimulation of somatotrophs with high K+ resulted in 50 discrete puncta
      per cell that were positive for growth hormone immunoreactivity. Identical
      stimulation of corticotrophs resulted in 150 puncta per cell that were anti
      adrenocorticotrophic hormone (ACTH) positive. However, unlike what was observed
      for lactotrophs, the number of structures containing retained growth hormone and
      ACTH decreased to less than 10% of the initial value in 80 min in somatotrophs
      and in less than 10 min in corticotrophs. Our results indicate that functional
      recycling of retained hormones is not shared by all anterior pituitary cell
      types.

PMID- 15480746
TI  - Influence of neonatal sympathectomy on proximal renal resistance artery function
      in spontaneously hypertensive rats.
AB  - Renal transplantation experiments have shown that the kidney contributes to
      chronic sympathectomy-induced arterial pressure reduction in spontaneously
      hypertensive rats (SHR). The underlying mechanisms are currently unclear but may
      include alterations in the function of small renal arteries. Neonatal SHR were
      sympathectomized by intraperitoneal guanethidine injections and removal of
      adrenal medullary tissue. Controls were sham- or hydralazine-treated. At 12 weeks
      of age, distal interlobar artery segments were investigated using small-vessel
      wire myography. Vessels from sympathectomized animals showed increased
      sensitivity to noradrenaline (NE). Vasopressin- and endothelin-1-induced
      vasoconstriction was similar in all groups (as reflected by the pD(2), i.e. 
      logEC(50), where EC(50) is the molar concentration of agonist eliciting a half
      maximal response). Maximum vasopressin-induced tension was similar in all groups
      while endothelin-1-induced maximum tension was significantly higher in
      sympathectomized than in sham-treated SHR. The sensitivity of NE-induced
      vasoconstriction to extracellular Ca(2+) did not differ between groups while
      sensitivity to L-type Ca(2+) channel activation was significantly higher in both
      sympathectomized and hydralazine-treated animals than in sham-treated animals.
      Endothelium-dependent and independent vasodilation were similar in all groups.
      Sequential blockade of NO-synthase and cyclooxygenase had similar effects in all
      groups. In conclusion, neonatal sympathectomy does not induce any changes in the
      function of isolated proximal renal resistance arteries from SHR that could
      explain the blood pressure lowering effect of a kidney graft from
      sympathectomized SHR.

PMID- 15480748
TI  - The effects of exogenous amino acids on the relaxant responses of pig urethral
      smooth muscle evoked by stimulation of the inhibitory nitrergic nerves.
AB  - Inhibitory innervation of urethral smooth muscle is mediated partly through
      release of NO. We investigated the mechanisms involved in the supply of the
      substrate L: -arginine to NO synthase by examining the relaxant response of the
      muscle to electrical field stimulation (EFS) and the effects of addition of amino
      acids to the bathing medium. Relaxant responses persisted during hours of
      repetitive stimulation but were enhanced rapidly by addition of L: -arginine (the
      "arginine paradox"). Addition of L: -lysine (competes with L: -arginine for
      transport on the y(+) carrier) and L: -glutamine (competing on the y(+)L carrier)
      attenuated the enhancement. Enhancement persisted after washing but was reversed
      by application of L: -lysine, suggesting that exogenous L: -arginine fills an
      intracellular pool and that L: -lysine can trans-stimulate its efflux from the
      pool. After prolonged depolarization in high-K(+), Na(+)-free solution the
      relaxant response became purely nitrergic. Addition of L: -arginine during the
      exposure continued to enhance the subsequent responses but L: -glutamine added
      with L: -arginine, could no longer reduce this enhancement. The results show the
      arginine paradox in inhibitory nerves and suggest the involvement of y(+) and
      y(+)L carriers in the transport of L: -arginine.

PMID- 15480747
TI  - Gastrin: old hormone, new functions.
AB  - It is exactly a century since the gastric hormone gastrin was first described as
      a blood-borne regulator of gastric acid secretion. The identities of the main
      active forms of the hormone (the "classical gastrins") and their cellular and
      molecular sites of action in regulating acid secretion have all attracted
      sustained attention. However, recent work on peptides derived from the gastrin
      precursor that do not stimulate acid secretion ("non-classical gastrins"),
      together with studies on mice over-expressing the gene, or in which the gastrin
      gene has been deleted, suggest hitherto unsuspected roles in regulating cell
      proliferation, migration, and differentiation. Moreover, microarray and proteomic
      studies have identified previously unsuspected target genes of the classical
      gastrins. Some of the newer actions have implications for our understanding of
      the progression to cancer in oesophagus, stomach, pancreas and colon, all of
      which have recently been linked in one way or another to dysfunctional signalling
      involving products of the gastrin gene. The present review focuses on recent
      progress in understanding the biology of both classical and non-classical
      gastrins.

PMID- 15480749
TI  - Inhibition of SERCA2 Ca(2+)-ATPases by Cs(+).
AB  - Replacement of K(+) with Cs(+) on the cytoplasmic side of the sarcoplasmic
      reticulum (SR) membrane reduces the maximum velocity (V(max)) of Ca(2+) uptake
      into the SR of saponin-permeabilized rat ventricular myocytes. To compare the
      sensitivity of the cardiac and smooth muscle/non-muscle forms of the
      sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a and -2b respectively)
      to replacement of K(+) with Cs(+), SERCA2a and SERCA2b were expressed in HEK-293
      cells. Ca(2+) uptake into HEK cell microsomes was inhibited by replacement of
      extravesicular K(+) with Cs(+) (V(max) of SERCA2a-mediated Ca(2+) uptake in CsCl
      was 80% of that in KCl; V(max) of SERCA2b-mediated uptake was 70% of that in
      KCl). The Ca(2+) sensitivity of uptake was decreased for both SERCA2a- and
      SERCA2b-mediated uptake and the Hill coefficients were increased in the presence
      of CsCl. The effects of Cs(+) on uptake were associated with direct inhibition of
      the ATPase activity of SERCA2a and SERCA2b. Our results indicate that cation
      binding sites are present in both SERCA2 isoforms, although the extent to which
      SERCA2b is inhibited by K(+) replacement is greater than that of SERCA2a or
      SERCA1. Consideration of these results and the recent molecular modeling work of
      others suggests that monovalent cations could interact with the Ca(2+) binding
      region of SERCA.

PMID- 15480750
TI  - Transport properties of the human intestinal anion exchanger DRA (down-regulated
      in adenoma) in transfected HEK293 cells.
AB  - Electroneutral NaCl absorption in the intestine is mediated by parallel Na+/H+
      and Cl-/HCO3- exchange. Mutations in the down-regulated in adenoma (DRA) gene
      cause congenital chloride diarrhoea but the transport characteristics of human
      DRA have not been studied in a heterologous human expression system. A N-terminal
      enhanced green fluorescence protein (EGFP)-tagged human DRA construct was
      therefore expressed stably in HEK293 cells. Cl-/HCO3- exchange was assessed by
      measuring intracellular pH and intracellular Cl- using fluorescent dyes.
      Expression of DRA resulted in the appearance of EGFP fluorescence and DRA
      immunoreactivity consistent with a location in the plasma membrane and possibly
      structures below the plasma membrane. DRA mediated electroneutral Cl-/HCO3-
      exchange but OH- was not transported and SO4(2-)/HCO3- exchange was minimal. In
      the presence of 5% CO2/HCO3- the apparent affinity of DRA for Cl- in transfected
      HEK cells was 23-36 mM, which is lower than that reported for rabbit ileal brush
      border membrane vesicles and for oocytes injected with human DRA. DRA was
      inhibited by 4 mM DIDS (45+/-11%), by 50 microM tenidap (71+/-8%) and by 100
      microM glibenclamide (59+/-22% inhibition of HCO3- transport and 79+/-3%
      inhibition of Cl- transport). The effects of DIDS and tenidap were not additive
      to those of glibenclamide.

PMID- 15480751
TI  - Ionic currents involved in shock-induced nonlinear changes in transmembrane
      potential responses of single cardiac cells.
AB  - An exhaustive characterization of how an isolated cardiac cell responds to
      applied electric fields could serve as an important groundwork for understanding
      responses of more complex higher order systems. Field stimulation of single
      cardiac cells during the early plateau of the action potential results in a
      nonuniform change in transmembrane potential (Vm) across the cell length that is
      more heavily weighted in the negative direction. These negatively shifted Vm
      responses are not replicated theoretically using present day membrane models. The
      goal of this study was to explore the membrane currents involved in the field
      responses during the plateau by selectively blocking various ion channels.
      Enzymatically isolated single guinea pig cells were stimulated with uniform field
      S1-S2 pulses, and the transmembrane potential responses were optically recorded
      from several sites along the cell length to assess the drug effect. We used nine
      different pharmacological agents to manipulate the conductance of major cardiac
      ion channels of which only barium (Ba2+) altered the transmembrane potential
      responses. At 50 microM Ba2+, which specifically blocks inwardly rectifying
      current I(K1), the negative shift in Vm responses was accentuated. At 1 mM Ba2+ ,
      which blocks both I(K1) and sustained plateau current I(Kp), the negative shift
      diminished. However, 1 mM Ba2+ also depolarized the cells, and depressed or
      completely eliminated the action potential. Based on these results we conclude
      that I(K1) contributes to field-induced responses during the plateau stimulation
      by passing a net inward current, which when blocked accentuates the negative
      shift in the Vm responses. A conclusive role of I(Kp) could not be demonstrated
      because of confounding changes in membrane potential. However, from our results
      it remains as the most viable candidate for the elusive current that contributes
      a net outward current to produce negatively weighted Vm responses during plateau
      stimulation and warrants further investigation.

PMID- 15480753
TI  - Catalase and alternative oxidase cooperatively regulate programmed cell death
      induced by beta-glucan elicitor in potato suspension cultures.
AB  - In potato (Solanum tuberosum L.) suspension cells, the expression of the gene
      encoding alternative oxidase (AOX) and H2O2 accumulation were induced by
      treatment with beta-glucan elicitor. The inhibition of catalase activity enhanced
      both AOX mRNA expression and the production of H2O2, whereas the ascorbate
      peroxidase inhibitor did not have any effect on these responses. Simultaneous
      inhibition of catalase and AOX activities in elicited cells dramatically
      increased H2O2 accumulation, leading to the disruption of mitochondrial membrane
      potential (deltapsi(m)) and programmed cell death (PCD). The results demonstrate,
      for the first time, that not only AOX but also catalase plays a central role in
      the suppression of mitochondrial deltapsi(m) breakdown and PCD induced by beta
      glucan elicitor.

PMID- 15480752
TI  - Invertebrate TRP proteins as functional models for mammalian channels.
AB  - Transient receptor potential (TRP) channels constitute a large and diverse family
      of channel proteins that are expressed in many tissues and cell types in both
      vertebrates and invertebrates. While the biophysical features of many of the
      mammalian TRP channels have been described, relatively little is known about
      their biological roles. Invertebrate TRPs offer valuable genetic handles for
      characterizing the functions of these cation channels in vivo. Importantly,
      studies in model organisms can help to identify fundamental mechanisms involved
      in normal cellular functions and human disease. In this review, we give an
      overview of the different TRP channels known in the two most utilized
      invertebrate models, the nematode Caenorhabditis elegans and the fruit-fly
      Drosophila melanogaster, and discuss briefly the heuristic impact of these
      invertebrate channels with respect to TRP function in mammals.

PMID- 15480754
TI  - Cloning of Brassica napus phospholipase C2 (BnPLC2), phosphatidylinositol 3
      kinase (BnVPS34) and phosphatidylinositol synthase1 (BnPtdIns S1)--comparative
      analysis of the effect of abiotic stresses on the expression of
      phosphatidylinositol signal transduction-related genes in B. napus.
AB  - The cloning and identification of full-length cDNA fragments coding for the
      Brassica napus phosphatidylinositol-specific phospholipase C2 (BnPLC2),
      phosphatidylinositol 3-kinase (BnVPS34) and phosphatidylinositol synthase
      (BnPtdIns S1) is described. In addition, two complementary fragments (120
      nucleotides long) corresponding to Arabidopsis PtdIns 4-kinase (PtdIns 4-K) and
      PtdIns-4-phosphate 5-kinase (PtdIns4P 5-K) sequences were chemically synthesized.
      These, as well as the cDNA clones, were used as probes to study the corresponding
      steady state mRNA levels in different tissues and developmental stages of B.
      napus, as well as in response to different environmental conditions. Transcripts
      corresponding to BnPLC2, BnPtdIns S1, BnVPS34 and PtdIns 4-K were found
      constitutively expressed at different levels in most tissues, with young leaves,
      siliques, and developing seeds showing the lowest levels. No detectable PtdIns4P
      5-K transcripts were found in buds or flowers. Up-regulation of BnPLC2 was seen
      in response to low temperature stress, which was notably accompanied by a
      parallel down-regulation of BnPtdIns S1, while BnVPS34 and PtdIns 4-K remained at
      control levels. A moderate increase in PtdIns4P 5-K levels was noted. In high
      salinity conditions BnPtdIns S1, BnVPS34 and BnPLC2 transcripts had similar
      responses but at different levels, with no major changes detected for PtdIns 4-K
      or PtdIns4P 5-K. Significantly, all five transcripts increased under drought
      stress conditions and all stressed plants clearly showed relatively higher levels
      of total inositol trisphosphate.

PMID- 15480755
TI  - The chloroplast NifS-like protein of Arabidopsis thaliana is required for iron
      sulfur cluster formation in ferredoxin.
AB  - Plastids are known to be able to synthesize their own iron-sulfur clusters, but
      the biochemical machinery responsible for this process is not known. In this
      study it is investigated whether CpNifS, the chloroplastic NifS-like cysteine
      desulfurase of Arabidopsis thaliana (L.) Heynh. is responsible for the release of
      sulfur from cysteine for the biogenesis of iron-sulfur (Fe-S) clusters in
      chloroplasts. Using an in vitro reconstitution assay it was found that purified
      CpNifS was sufficient for Fe-S cluster formation in ferredoxin in the presence of
      cysteine and a ferrous iron salt. Antibody-depletion experiments using stromal
      extract showed that CpNifS is also essential for the Fe-S cluster formation
      activity of chloroplast stroma. The activity of CpNifS in the stroma was 50- to
      80-fold higher than that of purified CpNifS on a per-protein basis, indicating
      that other stromal factors cooperate in Fe-S cluster formation. When stromal
      extract was separated on a gel-filtration column, most of the CpNifS eluted as a
      dimer of 86 kDa, but a minor fraction of the stromal CpNifS eluted at a molecular
      weight of approx. 600 kDa, suggesting the presence of a multi-protein complex.
      The possible nature of the interacting proteins is discussed.

PMID- 15480756
TI  - No symmetry advantage when object matching involves accidental viewpoints.
AB  - The presupposed advantage of symmetrical objects over asymmetrical objects was
      investigated in an object matching task, using accidental and non-accidental
      viewpoints. In addition, the accidental views could be symmetric or asymmetric.
      When two non-accidental views were presented, symmetrical objects were matched
      faster than asymmetrical objects. When an accidental view was presented first
      (followed by a non-accidental view), the matching of symmetrical objects was
      equal to that of asymmetrical objects. When a non-accidental view was presented
      first (followed by an accidental view), matching was again equal for the
      symmetrical and asymmetrical objects, although much faster compared with the
      opposite sequence of presented views. No effects of image symmetry in the
      accidental viewpoints were found. Apparently, the advantage of symmetrical
      objects over asymmetrical objects is only present in object matching when 3-D
      object structures are visible.

PMID- 15480757
TI  - Recollective experience in odor recognition: influences of adult age and
      familiarity.
AB  - We examined recollective experience in odor memory as a function of age,
      intention to learn, and familiarity. Young and older adults studied a set of
      familiar and unfamiliar odors with incidental or intentional encoding
      instructions. At recognition, participants indicated whether their response was
      based on explicit recollection (remembering), a feeling of familiarity (knowing),
      or guessing. The results indicated no age-related differences in the distribution
      of experiential responses for unfamiliar odors. By contrast, for familiar odors
      the young demonstrated more explicit recollection than the older adults, who
      produced more "know" and "guess" responses. Intention to learn was unrelated to
      recollective experience. In addition, the observed age differences in "remember"
      responses for familiar odors were eliminated when odor naming was statistically
      controlled. This suggests that age-related deficits in activating specific odor
      knowledge (i.e., odor names) play an important role for age differences in
      recollective experience of olfactory information.

PMID- 15480758
TI  - Structure, regulation, and function of micro1 in the sea urchin Hemicentrotus
      pulcherrimus.
AB  - The animal-vegetal axis of sea urchin embryos is morphologically apparent at the
      16-cell stage, when the mesomeres, macromeres, and micromeres align along it. At
      this stage, the micromere is the only autonomously specified blastomere that
      functions as a signaling center. We used a subtraction PCR survey to identify the
      homeobox gene micro1 as a micromere-specific gene. The micro1 gene is a
      representative of a novel family of paired-like class homeobox genes, along with
      PlHbox12 from Paracentrotus lividus and pmar1 from Strongylocentrotus purpuratus.
      In the present study, we showed that micro1 is a multicopy gene with six or more
      polymorphic loci, at least three of which are clustered in a 30-kb region of the
      genome. The micro1 gene is transiently expressed during early cleavage stages in
      the micromere. Recently, nuclear beta-catenin was shown to be essential for the
      specification of vegetal cell fates, including micromeres, and the temporal and
      spatial coincidence of micro1 expression with the nuclear entry of beta-catenin
      is highly suggestive. We demonstrated that micro1 is a direct target of beta
      catenin. In addition, we showed that micro1 is necessary and sufficient for
      micromere specification. These observations on the structure, regulation, and
      function of micro1 lead to the conclusion that micro1 and pmar1 (and potentially
      PlHbox12) are orthologous.

PMID- 15480759
TI  - Mutated otopetrin 1 affects the genesis of otoliths and the localization of
      Starmaker in zebrafish.
AB  - Otoliths in bony fishes and otoconia in mammals are composite crystals consisting
      of calcium carbonate and proteins. These biominerals are part of the gravity and
      linear acceleration detection system of the inner ear. Mutations in otopetrin 1
      have been shown to result in lack of otoconia in tilted and mergulhador mutant
      mice. The molecular function of Otopetrin 1, a novel protein that contains ten
      predicted transmembrane domains, however, has remained elusive. Here we show that
      a mutation in the orthologous gene in zebrafish is responsible for the complete
      absence of otoliths in backstroke mutants. We examined the localization of
      Starmaker, a secreted protein that is highly abundant in otoliths in backstroke
      mutants. Starmaker protein accumulated within cells of the otic epithelium,
      indicating a possible defect in secretion. Our data suggest that Otopetrin 1 in
      zebrafish may be involved in the protein trafficking of components required for
      formation of biominerals in the ear.

PMID- 15480760
TI  - Hypoblast controls mesoderm generation and axial patterning in the gastrulating
      rabbit embryo.
AB  - Gastrulation in higher vertebrate species classically commences with the
      generation of mesoderm cells in the primitive streak by epithelio-mesenchymal
      transformation of epiblast cells. However, the primitive streak also marks, with
      its longitudinal orientation in the posterior part of the conceptus, the anterior
      posterior (or head-tail) axis of the embryo. Results obtained in chick and mouse
      suggest that signals secreted by the hypoblast (or visceral endoderm), the
      extraembryonic tissue covering the epiblast ventrally, antagonise the mesoderm
      induction cascade in the anterior part of the epiblast and thereby restrict
      streak development to the posterior pole (and possibly initiate head development
      anteriorly). In this paper we took advantage of the disc-shape morphology of the
      rabbit gastrula for defining the expression compartments of the signalling
      molecules Cerberus and Dickkopf at pre-gastrulation and early gastrulation stages
      in a mammal other than the mouse. The two molecules are expressed in novel
      expression compartments in a complementary fashion both in the hypoblast and in
      the emerging primitive streak. In loss-of-function experiments, carried out in a
      New-type culturing system, hypoblast was removed prior to culture at defined
      stages before and at the beginning of gastrulation. The epiblast shows a stage
      dependent and topographically restricted susceptibility to express Brachyury, a T
      box gene pivotal for mesoderm formation, and to transform into (histologically
      proven) mesoderm. These results confirm for the mammalian embryo that the
      anterior-posterior axis of the conceptus is formed first as a molecular
      prepattern in the hypoblast and then irrevocably fixed, under the control of
      signals secreted from the hypoblast, by epithelio-mesenchymal transformation
      (primitive streak formation) in the epiblast.

PMID- 15480761
TI  - p16INK4a expression and progression risk of low-grade intraepithelial neoplasia
      of the cervix uteri.
AB  - The aim of the study was to evaluate the immunohistochemical expression of
      p16INK4a as a marker of progression risk in low-grade dysplastic lesions of the
      cervix uteri. p16INK4a immunohistochemistry was performed on 32 CIN1 with proven
      spontaneous regression of the lesion in the follow-up (group A), 31 (group B)
      with progression to CIN3 and 33 (group C) that were randomly chosen irrespective
      of the natural history of the lesion. p16INK4a staining pattern was scored as
      negative (less than 5% cells in the lower third of dysplastic epithelium
      stained), as focally positive (< or = 25%) and as diffuse positive (> 25%). A
      diffuse staining pattern was detected in 43.8% of CIN1 of group A, 74.2% of group
      B and 56.3% of group C. No p16INK4a staining was detected in 31.3% and 12.9% CIN1
      lesions of groups A and B, respectively. Overall, 71.4% and 37.8% of p16INK4a
      negative and diffusely positive CIN1 had regressed at follow-up, whereas 28.6%
      and 62.2% negative and diffusely positive CIN1 were progressed to CIN3,
      respectively (P < 0.05). All CIN3 lesions analyzed during follow-up of group B
      were diffusely stained for p16INK4a. Although p16INK4a may be expressed in low
      grade squamous lesions that undergo spontaneous regression, in this study, CIN1
      cases with diffuse p16INK4a staining had a significantly higher tendency to
      progress to a high-grade lesion than p16INK4a-negative cases. p16INK4a may have
      the potential to support the interpretation of low-grade dysplastic lesions of
      the cervix uteri.

PMID- 15480762
TI  - Combined mucormycosis and aspergillosis of the oro-sinonasal region in a patient
      affected by Castleman disease.
AB  - One case of aspergillosis and mucormycosis occurring in a patient with stage-IV
      Castleman disease was investigated. The patient, who had undergone
      polychemotherapy and was in otherwise good general condition, without
      lymphadenopathies or imbalance of the immune system, presented with a palatal
      ulceration that progressively involved the palatal mucosa and bone, the paranasal
      sinuses and the orbit. Repeated cultural examinations were always negative. He
      had undergone multiple cytological smears of the inflammatory infiltration and
      biopsies of both the oral and nasal mucosa, which resulted in extensive necrotic
      debris and suppurative inflammation, and, on the very last biopsy, fungal hyphae,
      spores and conidia were also detected. These were large, branching, mostly non
      septate hyphae, associated with conidiophores and conidia, the latter appearing
      dark brown to black in the histological preparations. Following the diagnosis of
      combined mucormycosis and aspergillosis, the patient underwent prolonged topic
      and systemic antibiotic treatment that resulted curative. Mucormycosis usually is
      a fatal complication of head and neck or systemic disorders, leading to severe
      immune suppression. Nevertheless, early diagnosis may be achieved using a
      combination of special stains and may lead to effective antibiotic treatment and
      cure of the patient, even if associated with other opportunistic infections, such
      as aspergillosis.

PMID- 15480763
TI  - Collecting duct carcinoma: an entity to be redefined?
AB  - Collecting duct carcinomas (CDCs) are highly aggressive tumors with poor survival
      at 1 year and are often metastatic at the time of diagnosis. It has been shown
      that patients may have better survival when treated with a chemotherapy regimen
      used for urothelial carcinoma. Such tumors must therefore be recognized, but
      their pathological diagnosis remains difficult. The two main differential
      diagnoses are renal pelvis urothelial carcinoma with infiltration of the kidney
      and/or high-grade and high-stage papillary renal cell carcinoma. The aim of our
      study was to compare the immunophenotype of 14 CDCs with 6 renal pelvis
      urothelial carcinomas (RPUC) infiltrating the medulla. The following markers were
      evaluated: ulex europeus aglutinin (UEA), peanuts aglutinin, vimentin and
      aquaporin 3 (AQP-3), a membrane component of normal collecting duct and
      urothelial cells. We were able to define a reproductive urothelial phenotype AQP
      3+, vimentin- and UEA+. Among the 14 CDCs, 10 cases demonstrated this
      immunophenotype. It coincided with an urothelial-like trabecular and tubular
      pattern. In contrast, the 4 remaining papillary CDCs had the inverse pattern, AQP
      3-, vimentin+ and UEA-. These results suggest that: (1) the trabecular and
      tubular variant of CDC with the urothelial AQP-3+, vimentin- phenotype can be
      included in the spectrum of urothelial diseases; (2) the papillary variant
      probably does not belong to the same entity; (3) AQP-3 is a marker of interest
      for improving the histological classification of CDC and unclassified aggressive
      renal tumors.

PMID- 15480764
TI  - Expression of CX3CL1 (fractalkine) in mice with endothelial-target rickettsial
      infection of the spotted-fever group.
AB  - Fractalkine (CX3CL1) is a chemokine expressed mainly by endothelial cells, which
      are the major cellular targets of rickettsiae. We used immunohistochemistry to
      investigate the normal expression of CX3CL1 in mice and the kinetics of
      expression of this chemokine throughout the course of lethal and sublethal
      rickettsial infections in a mouse model of spotted-fever group rickettsioses. The
      peak of expression of fractalkine on day 3 of infection coincided with the time
      of infiltration of macrophages into infected tissues and preceded the peak of
      rickettsial content in tissues.

PMID- 15480765
TI  - In angioimmunoblastic T-cell lymphoma, neoplastic T cells may be a minor cell
      population. A molecular single-cell and immunohistochemical study.
AB  - The significance of T-cell proliferations in angioimmunoblastic lymphoma (AILD)
      is still enigmatic. Although classified as a malignant T-cell lymphoma in the
      World Health Organisation lymphoma classification, some cases of AILD lack
      dominant T-cell clones. In a previous study, based on single-cell polymerase
      chain reaction (PCR), we obtained similar results as studies of AILD using
      Southern blot or conventional PCR: some cases of AILD contained large T-cell
      clones, and, in other cases, T-cell clones were undetectable. As in single-cell
      studies, only a limited number of cells could be investigated; thus, we wanted to
      gain more insight into the amount and distribution of tumour cells. By applying
      triple immunofluorescent staining with antibodies directed against T-cell
      receptor Vbeta-family-specific epitopes, we investigated T-cell populations in
      AILD and their localisation in the tissue in relation to B cells (CD20) and
      follicular dendritic cells (CD21). In two of five cases investigated, only a
      minority of the T-cells compartment belonged to the tumour clone. Neoplastic T
      cells were found throughout the tissue, including areas dominated by B cells.

PMID- 15480766
TI  - Accuracy of typing and grading invasive mammary carcinomas on core needle biopsy
      compared with the excisional specimen.
AB  - INTRODUCTION: Breast core needle biopsy (CNB) allows evaluation of histological,
      prognostic, and predictive factors in invasive mammary carcinomas (IMC). We
      tested the CNB accuracy on typing and grading of invasive breast carcinomas.
      MATERIALS AND METHODS: A histological review of 120 CNBs and their related
      surgical specimens was carried out in a double-blind fashion. Tumor type and
      grade were assigned according to the World Health Organization classification and
      the Nottingham grading system. RESULTS: The sum of CNB fragment lengths varied
      from 4 mm to 38 mm (mean 16.7 mm), and tumor sample size varied from 1 mm to 26
      mm (mean 11.1 mm). Histological type matched surgical specimen evaluation in 80
      of 120 cases (66.6%). Of the cases, 17 (14.2%) were changed to a different
      prognostic category. Histological grade comparison was accurate in 56 of 95 cases
      (59.0%, kappa=0.35). Histological grade components (tubule formation, nuclear
      grade, and mitotic index) agreed, respectively, in 54.7%, 58.9%, and 62.1% (kappa
      index 0.30, 0.36, and 0.28). DISCUSSION: Typing IMC on CNB can be routinely
      assessed based on good correlation with surgical specimens, especially
      considering prognostic categories for IMC. Grading IMC based on CNB is not as
      accurate, and its evaluation should be delayed until the surgical specimen
      examination. Tumor heterogeneity seems to be the most important factor for
      disagreement.

PMID- 15480767
TI  - Ciliated cyst of probable mullerian origin arising in the posterior mediastinum.

PMID- 15480768
TI  - Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid
      (Lennert's) variant are often derived from CD8(+) cytotoxic T-cells.
AB  - Nodal peripheral T-cell lymphomas are not well understood, and most of them are
      classified in the "not otherwise specified group" (PTCL-NOS). Data on their
      normal cellular derivation are ambiguous. Most peripheral T-cell lymphomas are
      composed of tumor cells and a (sometimes dominant) reactive background, which
      also includes resting and activated T-lymphocytes. We defined the phenotype of
      the tumor cells in 101 PTCL-NOS based on their cytological atypia and using
      immunohistochemical double stains on paraffin sections with CD4/Ki67 and
      CD8/Ki67. The results were correlated to clinical presentation and outcome.
      Lineage could be defined in 98 cases (97%). Tumor cells were CD4(+) in 43 cases
      and CD8(+) in 38. These presented at a younger age but a higher clinical stage
      compared with the CD4(+) lymphomas. In 15 cases, the atypical cells were CD4(
      )CD8(-); two cases were CD4(+)CD8(+). Of 17 lymphoepithelioid (Lennert's)
      lymphomas, 15 expressed CD8, one each was CD4(+) and CD4(-)CD8(-).

PMID- 15480769
TI  - Fas/FasL and perforin/granzyme pathway in acute rejection and diffuse alveolar
      damage after allogeneic lung transplantation-a human biopsy study.
AB  - Acute rejection and diffuse alveolar damage are major problems during the early
      time after transplantation. Against this background, lung biopsies after
      allogeneic lung transplantation were studied using immunohistochemistry. Biopsies
      with acute rejection, diffuse alveolar damage and morphological inconspicuous
      biopsies were chosen. The objectives of this study were to ascertain: (a) if and
      how CD4 and CD8 T cells contribute to allograft rejection and diffuse alveolar
      damage, (b) whether there is a correlation of the chemoattractant regulated on
      activation normal T cells (RANTES) with the mononuclear infiltrate and (c)
      whether perforin/granzyme and Fas/FasL pathways contribute to lung injury after
      lung transplantation. Our results show that CD4(+) and CD8(+) T cells were
      increased in biopsies with acute rejection and, to a minor extent, also in
      biopsies with diffuse alveolar damage due to reperfusion injury. RANTES
      expression of T cells was increased in biopsies with acute rejection. Perforin
      seemed to have a dual role in the alloimmune response. In one regard, it had a
      cytolytic function in the acute rejection process, and, in contrast, it may be
      responsible for downregulating both CD4- and CD8-mediated alloimmune responses.
      The FasL/Fas pathway is not only important for induction of apoptosis during
      rejection but is also a mechanism of lung injury in the development of diffuse
      alveolar damage.

PMID- 15480770
TI  - Characterization of the renal phenotype in a mouse model of Marfan syndrome.
AB  - The microfibrillar protein fibrillin-1 is expressed abundantly in the vasculature
      and the glomerulus of the kidney. Mutations in the fibrillin-1 gene lead to
      Marfan syndrome. The most common complication of this disease is aortic
      dilatation due to elastic deficiencies of the vascular wall. Several case reports
      describe glomerular disease in patients with Marfan syndrome, and fibrillin-1 has
      been implicated in nephrogenesis. To study the role of fibrillin-1 in renal
      development and function, we characterized the renal phenotype of fibrillin-1
      underexpressing mice. Kidney histology was evaluated by means of morphometry and
      stereology. Relative kidney weights, daily urine excretion, urinary albumin
      excretion, serum and urinary creatinine, as well as serum urea were not different
      than wild-type mice. Glomerular number and renal capillarization were normal. The
      size of the renal filtration surface was comparable in wild-type and fibrillin-1
      underexpressing mice. There was no indication for glomerular, renal vascular, or
      tubulointerstitial injury. However, glomerular volume and mesangial area were
      reduced. No changes in glomerular cell numbers were detected, but the cellular
      volume of mesangial cells was significantly lower in glomeruli of fibrillin-1
      underexpressing mice. Thus, despite the high abundance of fibrillin-1 in
      glomeruli of wild-type animals, underexpression of fibrillin-1 did not lead to
      functional deficiencies of the glomerulus. Alterations in renal histology were
      only subtle with a reduced glomerular volume and mesangial area likely due to a
      reduced mesangial cell volume.

PMID- 15480771
TI  - Second primary osteosarcoma with rosette-like structure in a patient with
      retinoblastoma.
AB  - A Japanese male patient developed bilateral retinoblastomas at the age of 1 year,
      but remained continuously disease-free after enucleation of the left eye and
      radiation therapy to the right eye. He noticed a painless hard mass around the
      right temporal bone when he was 25 years old. Biopsy specimen showed a small
      multi-nodular proliferation of tumor cells with prominent rosette-like
      structures. Eosinophilic material with focal mineralization was seen in the
      center of the rosettes. Immunostaining of the tumor cells showed positive
      reactions for epithelial membrane antigens CD 56 and CD 99. The patient was
      treated with systemic chemotherapy, and the tumor partially diminished. It is
      well known that a few osteosarcomas show a rosette-like appearance with
      production of osteoid in the center, but this is the first case of second primary
      osteosarcoma with prominent rosette-like features.

PMID- 15480772
TI  - Epstein-Barr-positive lymphoepithelial carcinoma and epi-myoepithelial cell
      carcinoma of the parotid gland: a hitherto unreported example of hybrid tumour.

PMID- 15480773
TI  - Loss of glia and neurons in the myenteric plexus of the aged Fischer 344 rat.
AB  - Over the normal lifespan, a subpopulation of myenteric neurons in the small and
      large intestines dies. This loss is one possible mechanism for the disruptions of
      gastrointestinal function seen in the elderly. Little, however, is known about
      how the glia constituting the supportive cells of the myenteric plexus may change
      with aging and the losses of the enteric neurons. The goal of the present study,
      therefore, was to determine what, if any, changes occur in the glia associated
      with myenteric neurons in the aged gut. Two experimental groups, consisting of
      adult (5-6 months of age, n = 8) or aged (26 months of age, n = 8) virgin male
      Fischer 344 rats, fed ad libitum, were examined. The duodenum, jejunum, ileum,
      colon, and rectum from each rat were prepared as whole mounts, and indirect
      immunofluorescence was used to visualize the myenteric glia and neurons
      (antibodies to S-100 and the HuC/D protein, respectively). Separate counts of
      glia and neurons from the same specimens were determined, and these counts were
      expressed both as per ganglionic area and as per ganglion to correct for
      "dilution" effects resulting from age-associated changes in tissue area.
      Significant reductions in both the numbers of glia as well as neurons occurred in
      every region of the small and large intestine sampled from aged rats, except for
      the rectum, where a nonsignificant decrease was observed. Glial loss was
      proportional to neuronal death, suggesting an interdependency between the two
      cell types. Thus, an understanding of the nature of the neuron-glia interaction
      in the enteric nervous system may provide insight into the deterioration of
      function seen in the aged gut.

PMID- 15480774
TI  - Growth hormone as an early embryonic growth and differentiation factor.
AB  - In this review we consider the evidence that growth hormone (GH) acts in the
      embryo as a local growth, differentiation, and cell survival factor. Because both
      GH and its receptors are present in the early embryo before the functional
      differentiation of pituitary somatotrophs and before the establishment of a
      functioning circulatory system, the conditions are such that GH may be a member
      of the large battery of autocrine/paracrine growth factors that control embryonic
      development. It has been clearly established that GH is able to exert direct
      effects, independent of insulin-like growth factor-I (IGF-I), on the
      differentiation, proliferation, and survival of cells in a wide variety of
      tissues in the embryo, fetus, and adult. The signaling pathways behind these
      effects of GH are now beginning to be determined, establishing early
      extrapituitary GH as a bona fide developmental growth factor.

PMID- 15480775
TI  - Ontogeny of intrinsic innervation in the human kidney.
AB  - We aimed to define, for the first time, the ontogeny of intrarenal innervation
      and to assess the distribution and nature of parenchymal nerves in the human
      fetal kidney. Our material consisted of routinely-processed renal tissue sections
      from 17 human fetuses, six of 20-24 gestational weeks (gw) and 11 of 25-40 gw,
      and three adults. We used immunohistochemistry with antibodies to the pan-neural
      markers neuron-specific enolase (NSE), neurofilaments (NF), PGP9.5, S100, and the
      adrenergic marker tyrosine hydroxylase (TH). NSE-, NF-, S100-, and PGP9.5
      positive nerves, associated with arterial and venous vasculature, were identified
      in the renal cortex from 20 gw onwards, and their density appeared to increase
      with gestation, reaching adult levels at 28 gw. Most of the intrarenal nerves
      were TH-positive. Nerve fibers extended from the corticomedullary region to the
      outer cortex, reaching the renal capsule in the 3rd trimester. In detail, NSE-,
      NF-, S100-, PGP9.5-, and TH-immunoreactive fibers were observed in close
      apposition to the renal artery and its branches, occasionally reaching the
      afferent and efferent arteriole (3rd trimester). Nerve fibers were detected in
      close apposition to the juxtaglomerular apparatus in the 2nd and 3rd trimesters.
      In the renal medulla, NSE-, PGP9.5-, S100-, and TH-positive nerve fibers were
      detected close to tubular cells as early as 20 gw. However, their density
      gradually decreased during the 3rd trimester, and they were not observed in the
      medulla of the adult kidney. In conclusion, the human fetal kidney appears richly
      innervated during the 2nd and 3rd trimesters. There is a progressive increase in
      the density of parenchymal nerve fibers towards term from the corticomedullary
      region to the cortex. Most intrarenal nerves are adrenergic and have a
      predominant perivascular distribution, implying that renal innervation plays an
      important functional role during intrauterine life.

PMID- 15480776
TI  - Acceptance of extended newborn screening: the problem of parental non-compliance.

PMID- 15480777
TI  - Compliance with science: consent or coercion in newborn screening.

PMID- 15480778
TI  - Multiple polypoid masses in the gastrointestinal tract in patient with Menkes
      disease on copper-histidinate therapy.

PMID- 15480779
TI  - High prevalence of coeliac disease in siblings of children with type 1 diabetes.
AB  - Coeliac disease has been shown to occur more frequently among first-degree
      relatives of diabetic patients than in the general population. Our objective was
      to assess the prevalence of endomysium antibodies (EMA) in non-diabetic siblings
      of Czech diabetic children and to evaluate the effects of HLA-DQ polymorphisms in
      determining the genetic susceptibility to coeliac disease (CD) in these subjects.
      We investigated 240 siblings of diabetic children from 213 families (125 males
      and 115 females, aged 12.6+/-4.9 years, mean +/- SD). All subjects were tested
      for the total IgA level to exclude IgA deficiency, and for endomysium IgA to
      disclose CD. In five IgA-deficient subjects, anti-gliadin IgG was used instead.
      Small bowel biopsy was offered to subjects with confirmed positive EMA. The HLA
      DQA1, -DQB1 genotypes were determined using PCR-SSP. Positive EMA were found in
      9/240 (3.8%) subjects (three males, six females). The biopsy confirmed CD in six
      children, two had a normal mucosal finding and one refused the biopsy. The HLA
      DQ2 polymorphism was more frequent among siblings with EMA (seven of nine) than
      in siblings without EMA (33%), corrected P = 0.031. CONCLUSION: The 3.8%
      frequency of coeliac disease found in siblings of diabetic children is close to
      the 4.3% found previously in Czech children with type 1 diabetes mellitus and is
      substantially higher than the rate in the healthy children population.

PMID- 15480780
TI  - High-frequency oscillatory ventilation in paediatric patients with acute
      respiratory distress syndrome--early rescue use.
AB  - In order to determine the response to high-frequency oscillatory ventilation
      (HFOV), used as an "early rescue" therapy, in a cohort of paediatric patients
      with acute respiratory distress syndrome (ARDS), a prospective clinical study was
      performed in a tertiary care paediatric intensive care unit. Ten consecutive
      patients, aged 12 days to 5 years with ARDS and hypoxaemic respiratory failure on
      conventional ventilation (CV), using a lung protective strategy, were managed
      with HFOV early in the course of the disease process (median length of CV 4 h).
      Arterial blood gases, oxygenation index (OI), alveolar-arterial oxygen difference
      (P(A-a)O2) and PaO2/FIO2 ratio were prospectively recorded prior to HFOV (0 h)
      and at predetermined intervals throughout the course of the HFOV protocol. There
      was a significant improvement in PaCO2 4 h after institution of HFOV (P = 0.012).
      A significant and sustained increase (P < 0.001) in PaO2/FIO2 ratio and a
      significant and sustained decrease (P < 0.001) in OI and P(A-a)O2 were
      demonstrated during the HFOV trial. These improvements were achieved 4 h after
      initiating HFOV (P < 0.05). Eight patients survived. There were no deaths from
      respiratory failure. CONCLUSION: In paediatric patients with acute respiratory
      distress syndrome and hypoxaemic respiratory failure on conventional ventilation,
      using a lung protective strategy, high-frequency oscillatory ventilation used as
      an "early rescue" therapy, improves gas exchange in a rapid and sustained fashion
      and provides a good outcome. Use of this therapy should probably be considered
      early in the course of the disease process.

PMID- 15480781
TI  - Basement membrane proteins play an active role in the invasive process of human
      hepatocellular carcinoma cells with high metastasis potential.
AB  - PURPOSE: Cell-matrix adhesive interaction has an important role in the invasive
      process of tumor cells, and integrins are the major receptors mediating cell
      matrix adhesion. The current study is to investigate the modulation of basement
      membrane (BM) proteins, especially collagen IV (C IV), laminin (LN), and
      fibronectin (FN) in the invasive processes of human hepatocellular carcinoma
      (HCC) cells in vitro, and to reveal the roles of beta1 integrins and RGD
      containing oligopeptide in the cell-matrix interaction. METHODS: Static adhesion
      assay was performed to study the rates of adhesion of MHCC97-H cells, treated or
      untreated with anti-beta1 (2 microg ml(-1)) and GRGDS, to C IV (50 microg ml(
      1)), LN (50 microg ml(-1)) or FN (50 microg ml(-1)). Gelatin zymography was used
      to detect the secretion of MMPs in the conditioned medium of MHCC97-H cells
      incubated 24 h by C IV, LN or FN, and interactions with anti-beta1 and GRGDS.
      Transwell chamber assay was used to investigate the influence of C IV, LN or FN,
      interacting with anti-beta1 and GRGDS, on the cellular mobility of MHCC97-H
      cells. RESULTS: Compared with blank control group, MHCC97-H cells showed
      significantly higher rates of adhesion to C IV, LN, and FN. Pretreatment with
      anti-beta1 could suppress adhesion to C IV, LN or FN, but GRGDS inhibited
      adhesion to FN (P<0.05) only. LN and FN could stimulate the secretion of MMPs by
      MHCC97-H cells cultured in vitro, especially MMP-9 and its activated type.
      Treatment with anti-beta1 could partly counteract the effects of LN and FN. GRGDS
      could prominently induce the secretion of MMPs, but the effect could be inhibited
      by pretreatment of anti-beta1. The results of Transwell chamber assay showed that
      LN, FN, and GRGDS could increase the number of tumor cells penetrating the
      microporous membrane, but the data of C IV did not reach significance. The
      effects were partly counteracted by anti-beta1. CONCLUSION: BM proteins play an
      active role in the invasive process of human hepatocellular carcinoma cells.
      Integrin beta1 is an important molecule which mediates the cell-matrix adhesive
      interaction of tumor cells. RGD-containing peptides competitively combine with
      the binding site of integrin beta1, and the effects of FN are RGD sequence
      dependent.

PMID- 15480782
TI  - Clinical response to induction chemotherapy predicts local control and long-term
      survival in multimodal treatment of patients with locally advanced esophageal
      cancer.
AB  - PURPOSE: From 1991 to 1994 we performed a phase II study with intensive
      preoperative chemoradiation in locally advanced squamous cell carcinoma and
      adenocarcinoma of the esophagus. We now report on a multivariate analysis of
      prognostic factors based on the long-term results at a median follow-up of 6.5
      years. PATIENTS AND METHODS: Eighty-eight patients were treated. Prognostic
      factors for overall survival and local tumor control were identified by
      univariate and multivariate analysis. RESULTS: Median overall survival reached 17
      months, and the survival rate at 5 years was 22% (95%-confidence interval: 18
      26%). Response to induction chemotherapy was the only independent factor
      predicting local tumor control and--beside weight loss prior to treatment--it
      also proved to be an independent prognostic factor for long-term survival.
      CONCLUSIONS: Intensive chemoradiation followed by surgery seems to be appropriate
      to improve long-term survival of high-risk patients with locally advanced
      esophageal cancer. In our trial, local tumor control and prognosis were best
      correlated with response to induction chemotherapy. These results may help to
      guide decisions regarding surgery in multimodal treatment of EC. Further efforts
      are needed to increase the number of treatment responders and to predict tumors
      not responding to chemo(radio)therapy earlier.

PMID- 15480783
TI  - Listeria monocytogenes produces a pro-invasive factor that signals via
      ErbB2/ErbB3 heterodimers.
AB  - PURPOSE: We have previously demonstrated that conditioned medium from bacteria,
      some of which were isolated from the colon of cancer patients, stimulate cancer
      cell invasion in vitro through a 13-mer beta-casein-derived peptide. Since
      invasion signalling pathways are coordinated by the balance between protein
      kinases and phosphatases, we investigated the effect of conditioned medium from
      bacteria on the overall cellular tyrosine phosphorylation. METHODS: The tyrosine
      phosphorylation level of HCT-8/E11 human colon cancer cells treated with the pro
      invasive conditioned medium of Listeria, prepared on top of collagen type I gels
      (CM(Coll) Listeria/TSB), were analysed by means of immunoprecipitation and
      Western blot, with specific anti-phosphotyrosine antibodies. RESULTS: We
      demonstrated that CM(Coll) Listeria/TSB increases the tyrosine phosphorylation
      level of ErbB2 and ErbB3, members of the epidermal growth factor receptor (EGFR)
      family, and the association between ErbB3 and the phosphatidylinositol 3-kinase
      (PI3K) regulatory subunit (p85alpha). CM(Coll) Listeria/TSB-stimulated ErbB3
      tyrosine phosphorylation and cancer cell invasion were independent from EGFR
      expression and activity but dependent on ErbB2 activity. CONCLUSIONS: The
      interaction between Listeria and collagen type I produces, next to the 13-mer
      peptide, at least another pro-invasive factor that signals via ErbB2/ErbB3
      heterodimers.

PMID- 15480784
TI  - Steinernema glaseri Santa Rosa strain (Rhabditida: Steinernematidae) and
      Heterorhabditis bacteriophora CCA Strain (Rhabditida: Heterorhabditidae) as
      biological control agents of Boophilus microplus (Acari: Ixodidae).
AB  - The present study was carried out to evaluate the action of Steinernema glaseri
      Santa Rosa strain and Heterorhabditis bacteriophora CCA strain as biological
      control agents of Boophilus microplus. Engorged females ticks were distributed on
      Petri dishes containing different concentrations of infective juvenile (IJ)
      nematodes (0, 375, 500, 750, 1,500, 2,500, 5,000 and 25,000). The data showed a
      reduction of approximately 90% in the eggs laid at a concentration of 5,000 S.
      glaseri IJs and approximately 80% at a concentration of 1,500 H. bacteriophora
      IJs. The female mortality increased linearly with the increase in S. glaseri
      concentrations. However, in the tests with H. bacteriophora this linearity was
      not observed. The effectiveness of the treatment with both species of
      entomopathogenic nematodes was compatible with other control methods. The results
      show the potential of S. glaseri and H. bacteriophora as biological control
      agents for the control of B. microplus under laboratory conditions.

PMID- 15480785
TI  - Molecular cloning and characterization of cDNA encoding a ubiquitin-conjugating
      enzyme from Clonorchis sinensis.
AB  - The ubiquitin-proteasome system is an essential mechanism for protein degradation
      in eukaryotes. Protein ubiquitination is composed of a series of enzymatic
      reactions. The ubiquitin-conjugating enzyme (E2) is one of the important enzymes
      involved in the process. A cDNA encoding an E2 enzyme was cloned from a
      Clonorchis sinensis cDNA library by large-scale sequencing. This new cDNA
      contains 862 bp with a putative open reading frame of 156 amino acids. The
      deduced amino acid sequence is 77% identical to the human E2, HHR6A and HHR6B.
      The coding region of this cDNA was expressed in E. coli as a GST-tagged protein,
      and was purified to electrophoretic homogeneity. Enzymatic assays showed that
      this E2 had the capacity to form a thiolester linkage, and could conjugate
      ubiquitin to histone H2A in an E3-independent manner in vitro, which indicated
      that the expressed protein was functionally active. The nucleotide sequence
      reported in this paper has been submitted to the Genbank Database with accession
      number AY632078.

PMID- 15480786
TI  - Fecal-oral transmission of the cyst form of Blastocystis hominis in rats.
AB  - The infectivity of two Blastocystis hominis strains, RN94-9 and NIH:1295:1, was
      examined in 3-week-old SPF Wistar rats. The NIH:1295:1 strain, originally
      isolated from a guinea pig, was only able to infect rats via intracecal
      inoculation of the cultured organisms, while the RN94-9 strain, originally
      isolated from a laboratory rat, was able to infect rats by oral inoculation of
      the cultures due to the presence of a cystic form in the in vitro culture. Since
      many cysts were discharged in the feces of the infected rats, the infectivity of
      the concentrated cysts was compared between the two strains. Successful oral
      infection was observed in rats inoculated with 1 x 10(2)-1 x 10(6) cysts of the
      RN94-9 and NIH:1295:1 strains. The infectivity of the ten cysts varied in the
      three experiments of ten rats, being 20-100% and 30-100% in the RN94-9 and
      NIH:1295:1 strains, respectively. When an uninfected normal rat was housed with
      five experimentally inoculated rats, the normal rat became infected,
      demonstrating the fecal-oral transmission of the cyst form of this parasite.
      These results show that the Wistar rat is an ideal host for the propagation of
      strains RN94-9 and NIH:1295:1 of B. hominis, and demonstrate that the cyst form
      is the only transmissible form of this parasite.

PMID- 15480787
TI  - Arabidopsis thaliana expresses multiple Golgi-localised nucleotide-sugar
      transporters related to GONST1.
AB  - Transport of nucleotide-sugars across the Golgi membrane is required for the
      lumenal synthesis of a variety of essential cell surface components, and is
      mediated by nucleotide sugar transporters (NSTs) which are members of the large
      drug/metabolite superfamily of transporters. Despite the importance of these
      proteins in plants, so far only two have been described, GONST1 and AtUTr1 from
      Arabidopsis thaliana. In this work, our aim was to identify further Golgi
      nucleotide-sugar transporters from Arabidopsis. On the basis of their sequence
      similarity to GONST1, we found four additional proteins, which we named GONST2,
      3, 4 and 5. These putative NSTs were grouped into three clades: GONST2 with
      GONST1; GONST3 with GONST4; and GONST5 with six further uncharacterized proteins.
      Transient expression in tobacco cells of a member of each clade, fused to the
      Green Fluorescent Protein (GFP), suggested that all these putative NSTs are
      localised in the Golgi. To obtain evidence for nucleotide sugar transport
      activity, we expressed these proteins, together with the previously characterised
      GONST1, in a GDP-mannose transport-defective yeast mutant (vrg4-2). We tested the
      transformants for rescue of two phenotypes associated with this mutation:
      sensitivity to hygromycin B and reduced glycosylation of extracellular chitinase.
      GONST1 and GONST2 complemented both phenotypes, indicating that GONST2, like the
      previously characterized GONST1, is a GDP-mannose transporter. GONST3, 4 and 5
      also rescued the antibiotic sensitivity, but not the chitinase glycosylation
      defect, suggesting that they can also transport GDP-mannose across the yeast
      Golgi membrane but with a lower efficiency. RT-PCR and analysis of Affymetrix
      data revealed partially overlapping patterns of expression of GONST1-5 in a
      variety of organs. Because of the differences in ability to rescue the vrg4 - 2
      phenotype, and the different expression patterns in plant organs, we speculate
      that GONST1 and GONST2 are both GDP-mannose transporters, whereas GONST3, GONST4
      and GONST5 may transport other nucleotide-sugars in planta.

PMID- 15480788
TI  - The ire1 and ptc2 genes involved in the unfolded protein response pathway in the
      filamentous fungus Trichoderma reesei.
AB  - A signal transduction pathway called the unfolded protein response is activated
      when increased levels of misfolded proteins or incorrectly assembled subunits
      accumulate in the endoplasmic reticulum (ER). The expression of several genes for
      ER-resident foldases and chaperones, as well as genes encoding proteins that are
      involved in functions associated with the secretory process, are induced by this
      pathway. This paper describes the cloning and characterisation of genes for two
      components of the pathway, ire1 and ptc2, from the filamentous fungus Trichoderma
      reesei (Hypocrea jecorina). The data presented demonstrates that the T. reesei
      genes can complement Saccharomyces cerevisiae mutants that are deficient in the
      corresponding homologues. The T. reesei IREI protein has intrinsic kinase
      activity, as revealed by an in vitro autophosphorylation assay. Overexpression of
      ire1 in a T. reesei strain that expresses a foreign protein (laccase 1 from
      Phlebia radiata), results in up-regulation of the UPR pathway, as indicated by
      the increased expression levels of the known UPR target genes bip1 and pdi1.
      Splicing of the mRNA encoding the transcription factor HAC1 is also observed.
      Other genes encoding proteins from different parts of the secretory pathway also
      respond to ire1 overexpression.

PMID- 15480789
TI  - Analysis of transcripts that are differentially expressed in three sectors of the
      rice root system under water deficit.
AB  - Short periods of water deprivation can stimulate the growth of seminal and
      lateral roots in rice, and inhibit the emergence of adventitious roots.
      Identification of genes in the different tissues that respond to a water deficit
      may help us to understand the mechanism underlying root growth under conditions
      when water is scarce. cDNA-amplified fragment length polymorphism (AFLP) analysis
      was used to profile gene expression upon imposition of water deficit in three
      types of root tissue from the upland rice variety Azucena: seminal root tips,
      lateral root zones and adventitious root primordial zones. In all, 121 unique
      transcript-derived fragments (TDFs) were cloned, and Northern analysis was
      carried out for 30 TDFs to confirm their expression patterns. Sixty-six TDFs were
      differentially expressed in all three root samples. Four (AC2, D6, L22 and T23)
      were up-regulated by water deficit in seminal root tips and lateral root zones,
      and down-regulated in adventitious root primordial zones, an expression pattern
      which reflects the phenotypic changes observed in the different root sectors. In
      contrast, T17 and T37 showed the opposite expression pattern in Azucena: up
      regulation in adventitious roots and repression in the other two zones. Functions
      could be assigned to five of these six TDFs on the basis of homology: they encode
      an expansin (T37), a fruit-ripening protein similar to ASR (T23), submergence
      induced protein 2A (T17), a dehydrin (D6) and a 9- cis -epoxycarotenoid
      dioxygenase1 (L22), respectively. AC2 did not show a significant match to any
      known gene. Northern analysis showed that these six clones exhibited expression
      patterns that differed between the two cultivars tested (Azucena and the lowland
      variety IR1552) with respect to regulation by water limitation. Furthermore, T17,
      T37, D6 and T23 mapped within intervals known to contain QTLs (quantitative trait
      loci) for root growth in rice under water deficit. These genes may regulate or co
      regulate the growth and development of the three root zones in a tissue-specific
      manner, and may play a role in the processes that underlie the early changes in
      root architecture under conditions of water deprivation.

PMID- 15480791
TI  - Pink (P), a new locus responsible for a pink trait in onions (Allium cepa)
      resulting from natural mutations of anthocyanidin synthase.
AB  - A new locus conditioning a pink trait in onions was identified. Unusual pink
      onions were found in haploid populations induced from an F(1) hybrid between
      yellow and dark red parents and in F(3) populations originating from the same
      cross. Segregation ratios of red to pink in F(2), backcross, and F(3) populations
      indicated that this pink trait is determined by a single recessive locus. RT-PCR
      was carried out to look for any differential expression of anthocyanin synthesis
      genes between dark red and pink F(3) lines. The transcript level of anthocyanidin
      synthase (ANS) was significantly reduced in the pink line. To determine whether
      this reduced transcription is caused by other regulatory factors or by mutations
      in the ANS gene itself, ANS gene sequences from both dark red and pink F(3) lines
      were compared to detect any polymorphisms. Polymorphisms were identified, and
      subsequently utilized as molecular markers for the selection of ANS alleles.
      Absolute co-segregation of the pink allele and the ANS allele from the pink line
      was observed in parents, F(1) and F(3) populations. These results indicate that
      reduced transcription of the ANS gene caused by mutations in a cis -acting
      element is likely to result in the pink trait in onions.

PMID- 15480790
TI  - Genetic analysis of the biosynthesis of non-ribosomal peptide- and polyketide
      like antibiotics, iron uptake and biofilm formation by Bacillus subtilis A1/3.
AB  - The Bacillus subtilis strain A1/3 shows exceptionally diverse antibiotic
      capacities compared to other B. subtilis strains. To analyze this phenomenon,
      mutants for the putative pantotheinyltransferase gene (pptS), and for several
      genes involved in non-ribosomal peptide synthesis and polyketide synthesis were
      constructed and characterized, using bioassays with blood cells, bacterial and
      fungal cells, and mass spectrometry. Among at least nine distinct bioactive
      compounds, five antibiotics and one siderophore activity were identified. The
      anti-fungal and hemolytic activities of strain A1/3 could be eliminated by
      mutation of the fen and srf genes essential for the synthesis of fengycins and
      surfactins. Both pptS- and dhb -type mutants were defective in iron uptake,
      indicating an inability to produce a 2,3-dihydroxybenzoate-type iron siderophore.
      Transposon mutants in the malonyl CoA transacylase gene resulted in the loss of
      hemolytic and anti-fungal activities due to the inhibition of bacillomycin L
      synthesis, and this led to the discovery of bmyLD-LA-LB* genes. In mutants
      bearing disruption mutations in polyketide (pksM- and/or pksR -like) genes, the
      biosynthesis of bacillaene and difficidins, respectively, was inactivated and was
      accompanied by the loss of discrete antibacterial activities. The formation of
      biofilms (pellicles) was shown to require the production of surfactins, but no
      other lipopeptides, indicating that surfactins serve specific developmental
      functions.

PMID- 15480792
TI  - Isolation of an active element from a high-copy-number family of retrotransposons
      in the sweetpotato genome.
AB  - A large number of plant retrotransposons have been characterized, but only three
      families ( Tnt1, Tto1 and Tos17) have been demonstrated to be transpositionally
      competent. We have used a novel approach to identify an active member of the Ty1-
      copia retrotransposon family with estimated 400 copies in the sweetpotato genome.
      Ty1- copia reverse transcriptase (RTase) sequences from the sweetpotato genome
      were analyzed, and a group of retrotransposon copies that probably arose by
      recent transposition events was identified and analyzed further. Transcripts
      containing long terminal repeats (LTRs) of this group were amplified from callus
      cDNA by the 3'RACE technique. Patterns of sequence-specific amplification
      polymorphism (S-SAP) of the LTR sequences in genomic DNA were compared between a
      normal plant and callus lines derived from it. In this way, a callus-specific S
      SAP product was identified, which apparently resulted from the insertion of the
      retrotransposon detected by 3'RACE during cell culture. We conclude that our
      approach provides an effective way to identify active elements among the members
      of high-copy-number retrotransposon families.

PMID- 15480793
TI  - Diet and the frequency of the alanine:glyoxylate aminotransferase Pro11Leu
      polymorphism in different human populations.
AB  - The intermediary metabolic enzyme alanine:glyoxylate aminotransferase (AGT)
      contains a Pro11Leu polymorphism that decreases its catalytic activity by a
      factor of three and causes a small proportion to be mistargeted from its normal
      intracellular location in the peroxisomes to the mitochondria. These changes are
      predicted to have significant effects on the synthesis and excretion of the
      metabolic end-product oxalate and the deposition of insoluble calcium oxalate in
      the kidney and urinary tract. Based on the evolution of AGT targeting in mammals,
      we have previously hypothesised that this polymorphism would be advantageous for
      individuals who have a meat-rich diet, but disadvantageous for those who do not.
      If true, the frequency distribution of Pro11Leu in different extant human
      populations should have been shaped by their dietary history so that it should be
      more common in populations with predominantly meat-eating ancestral diets than it
      is in populations in which the ancestral diets were predominantly vegetarian. In
      the present study, we have determined frequency of Pro11Leu in 11 different human
      populations with divergent ancestral dietary lifestyles. We show that the
      Pro11Leu allelic frequency varies widely from 27.9% in the Saami, a population
      with a very meat-rich ancestral diet, to 2.3% in Chinese, who are likely to have
      had a more mixed ancestral diet. FST analysis shows that the differences in
      Pro11Leu frequency between some populations (particularly Saami vs Chinese) was
      very high when compared with neutral loci, suggesting that its frequency might
      have been shaped by dietary selection pressure.

PMID- 15480794
TI  - High dose of glucose promotes chondrogenesis via PKCalpha and MAPK signaling
      pathways in chick mesenchymal cells.
AB  - We investigated the molecular mechanism of the glucose effect on the regulation
      of chondrogenesis. Exposure of chick wing bud mesenchymal cells to high
      concentrations of glucose stimulated chondrogenesis 2-fold to 2.5-fold without
      affecting cell proliferation. Glucose increased protein levels and the membrane
      translocation of protein kinase C alpha (PKCalpha), leading to a reduction of
      extracellular signal-regulated kinase (ERK) phosphorylation. Phosphorylation of
      p38 was also increased in a PKC-independent manner by glucose treatment. Glucose
      also increased cell adhesion molecules such as fibronectin, integrin beta1, and N
      cadherin at early stages and then decreased these adhesion molecules at later
      stages of chondrogenesis. These alterations in protein level of adhesion
      molecules and in the phosphorylation of mitogen-activated protein kinases by
      glucose were blocked by inhibition of PKC or p38 but were synergistically
      increased by the inhibition of ERK. Therefore, high doses of glucose induce the
      down-regulation of ERK activity via PKCalpha and the up-regulation of p38 and
      result in the stimulation of chondrogenesis of chick mesenchymal cells through
      modulating the expression of adhesion molecules.

PMID- 15480795
TI  - Identification of a neurofilament-like protein in the protocerebral tract of the
      crab Ucides cordatus.
AB  - Neurofilaments (NFs) have not been observed in crustaceans using conventional
      electron microscopy, and intermediate filaments have never been described in
      crustaceans and other arthropods by immunocytochemistry. Since polypeptides,
      labeled by the NN18-clone antibody, were revealed on microtubule side-arms of
      crayfish, we have tested, in this study, whether proteins similar to mammalian
      NFs are present in the protocerebral tract (PCT) of the crab Ucides cordatus. We
      used immunohistochemistry for light microscopy with monoclonal antibodies against
      three different NF subunits, high (NF-H), medium (NF-M), and light (NF-L).
      Labeling was observed with the NN18-clone, which recognizes NF-M. In order to
      confirm the results obtained with the immunohistochemical reactions, Western
      blotting, using the three primary antibodies, was performed and the presence of
      NF-M was confirmed. The NN18-clone monoclonal antibody recognized a protein of
      approximately 160 kDa, similar to the mammalian NF-M protein, but NF-L and NF-H
      were not recognized. Conventional transmission electron microscopy was used to
      observe the ultrastructural components of the axons and immunoelectron microscopy
      was used to show the distribution of the NF-M-like polypeptides along
      cytoskeletal elements of the PCT. Our results agree with previous studies on
      crustacean NF proteins that have reported negative immunoreactions against NF-H
      and NF-L subunits and positive immunoreactions against the mammalian NF-M
      subunit. However, the protein previously referred to as P600 and recognized by
      the NN18-clone, has a very high molecular weight, thus, being different from
      mammalian NF-M subunit and from the protein revealed now in our study.

PMID- 15480796
TI  - Extracellular matrix distribution and islet morphology in the early postnatal
      pancreas: anomalies in the non-obese diabetic mouse.
AB  - Previously, we reported elevated numbers of macrophages in the pancreas of NOD
      mice, a spontaneous animal model for T1D, during the early postnatal period.
      Extracellular matrix plays an important role in the tissue trafficking and
      retention of macrophages as well as in postnatal pancreas development. Therefore,
      we have examined the expression and distribution of laminin and fibronectin, two
      major extracellular matrix proteins and their corresponding integrin receptors,
      in the pre-weaning pancreases of NOD mice and control mouse strains. In addition,
      we have characterized the pancreas morphology during this period, since the
      morphology of the pre-weaning pancreas before the onset of lymphocytic peri
      insulitis, when the pancreas is still subject to developmental changes, has been
      poorly documented. We show that laminin labeling is mainly associated with
      exocrine tissue, whereas fibronectin labeling was mostly localized at the islet
      ductal pole, islet periphery and in intralobular septa. Moreover, the protein
      expression level of fibronectin was increased in NOD pancreases at the early
      stage of postnatal development, as compared to pancreases of C57BL/6 and BALB/c
      mouse strains. Interestingly, pancreatic macrophages were essentially found at
      sites of intense fibronectin labeling. The increased fibronectin content in NOD
      neonatal pancreas coincided with altered islet morphology, histologically
      reflected by enlarged and irregular shaped islets and increased percentages of
      total endocrine area as compared to that of control strains. In conclusion,
      increased levels of the extracellular matrix protein fibronectin were found in
      the early postnatal NOD pancreas, and this is associated with an enhanced
      accumulation of macrophages and altered islet morphology.

PMID- 15480797
TI  - Involvement of keratinocyte growth factor (KGF)-KGF receptor signaling in
      developmental estrogenization syndrome of mouse vagina.
AB  - Exposure of mice to estrogen or keratinocyte growth factor (KGF) in vivo during
      the neonatal period results in estrogen-independent persistent proliferation and
      cornification of the vaginal epithelium when the animals become adults. Here,
      whether and how KGF-signaling is involved in the effects of estrogen on the
      neonatal mouse vagina were studied with an in vitro method. Newborn mouse vaginae
      were cultured for 3 days in serum-free medium containing various combinations of
      estradiol-17beta (E2), KGF, anti-KGF antibody, KGFR inhibitory peptide and
      heparin, and then transplanted into ovariectomized host mice for 35 days. The
      vaginae cultured with 5 microg/ml E2 or 5 microg/ml KGF had a cornified thick
      epithelium, while the epithelium of the vehicle-treated controls stayed thin. The
      E2 effect was blocked by concurrent treatment with anti-KGF antibody or KGFR
      inhibitory peptide. KGF treatment alone at doses less than 500 ng/ml did not
      induce permanent vaginal changes but such changes did occur in vaginae treated
      with heparin plus as little as 10 ng/ml KGF. On the other hand, heparin inhibited
      the permanent vaginal changes induced by estrogen. These results suggest that
      irreversible vaginal changes are induced by the direct action of KGF on the
      developing vagina and that the developmental estrogenization syndrome of mouse
      vagina is caused by intensification of endogenous KGF/KGFR signaling by exogenous
      estrogen.

PMID- 15480798
TI  - Myogenesis during holothurian intestinal regeneration.
AB  - Echinoderms are well known as being able to regenerate body parts and thus
      provide excellent models for studying regenerative processes in adult organisms.
      We are interested in intestinal regeneration in the sea cucumber, Holothuria
      glaberrima, and focus here on the regeneration of intestinal muscle components.
      We have used immunohistochemical techniques to describe the formation of the
      intestinal muscle layers. Myoblasts are first observed within the regenerating
      structure, adjacent to the coelomic epithelia. Within a few days, these cells
      acquire muscle markers and form a single cell layer that underlies the epithelia.
      Animals injected with BrdU at various regeneration stages have been subsequently
      analyzed for the presence of muscle differentiation markers. BrdU-labeled muscle
      nuclei are observed in myocytes of 3-week regenerates, showing that these cells
      originate from proliferating precursors. The peak in muscle precursor
      proliferation appears to occur during the second week of regeneration. Therefore,
      new muscle cells in the regenerating intestine originate from precursors that
      have undergone cell division. Our results suggest that the precursor cells arise
      from the coelomic epithelia. We also provide a comparative view of muscle
      regeneration in an echinoderm, a topic of interest in view of the many recent
      studies of muscle regeneration in vertebrate species.

PMID- 15480799
TI  - Mas-allatotropin/Lom-AG-myotropin I immunostaining in the brain of the locust,
      Schistocerca gregaria.
AB  - Mas-allatotropin (Mas-AT) and Lom-accessory gland-myotropin I (Lom-AG-MTI) are
      two members of a conserved family of insect neuropeptides, collectively termed
      allatotropins, which have diverse functions, ranging from stimulation of juvenile
      hormone secretion to myotropic effects on heart and hindgut. In addition,
      allatotropins appear to be abundant within the nervous system, suggesting
      neuroactive roles. To identify neurons in the insect brain suitable for a
      neurophysiological analysis of the roles of allatotropins, we used antisera
      against Mas-AT and Lom-AG-MTI to map allatotropin-immunoreactive neurons in the
      brain of a suitable insect, the locust Schistocerca gregaria. Both antisera
      revealed basically identical staining patterns throughout the locust brain with
      more than 12,500 immunostained interneurons per brain hemisphere. Neurosecretory
      cells were not labeled, and the retrocerebral complex was devoid of
      immunostaining. Prominent immunoreactive cell types include about 9,600 lamina
      monopolar neurons, medulla to lobula interneurons, local neurons of the antennal
      lobe, a giant interneuron of the mushroom body, projection neurons of the
      glomerular lobe to the mushroom body, and three systems of tangential neurons of
      the central complex. Several groups of neurons showed colocalization of Mas-AT-
      and gamma-aminobutyric acid immunostaining. Mass spectrometric analysis
      identified a peptide with a molecular mass identical to Lom-AG-MTI in all major
      parts of the locust brain but not in the retrocerebral complex. This study
      strongly suggests that Lom-AG-MTI is highly abundant in the locust brain, and is
      likely to play a neuroactive role in many brain circuits including all stages of
      sensory processing, learning and memory, and higher levels of motor control.

PMID- 15480800
TI  - Hatching asynchrony in Burrowing Owls is influenced by clutch size and hatching
      success but not by food.
AB  - In most animals, siblings from a given reproductive event emerge over a very
      short period of time. In contrast, many species of birds hatch their young
      asynchronously over a period of days or weeks, handicapping last-hatched chicks
      with an age and size disadvantage. Numerous studies have examined the adaptive
      significance of this atypical hatching pattern, but few have attempted to explain
      the considerable intrapopulation variation that exists in hatching asynchrony. I
      explored proximate determinants of hatching asynchrony by monitoring 112
      Burrowing Owl (Athene cunicularia) nests in the grasslands of southern
      Saskatchewan, Canada, over 4 years. Age disparities between first- and last
      hatched siblings (i.e., hatching spans) varied considerably, ranging between 1
      and 7 days (mode = 4 days). These hatching spans increased with increased
      hatching success. Hatching spans also increased with larger clutches, but the
      increase was less than predicted given the increased time required to lay more
      eggs. Hatching span was unrelated to number of prey cached in the nest during egg
      laying (an index of food availability), and was unaltered by a year of super
      abundant prey. Furthermore, pairs given extra food during laying had hatching
      spans equal to those of unsupplemented control pairs. These results were
      inconsistent with both the energy constraint and facultative manipulation
      hypotheses, which predict that hatching asynchrony should vary with the level of
      food during laying, when incubation onset is determined. Burrowing Owls were
      apparently free of food limitation early in breeding, yet may not have been able
      to optimize hatching spans because food conditions during laying were largely
      unrelated to food conditions during brooding. Thus, one of the premises for
      facultative manipulation of hatching asynchrony-that laying females are able to
      forecast post-hatch food conditions-may not have been met for this population of
      Burrowing Owls.

PMID- 15480801
TI  - The influence of climate on the timing and rate of spring bird migration.
AB  - Ecological processes are changing in response to climatic warming. Birds, in
      particular, have been documented to arrive and breed earlier in spring and this
      has been attributed to elevated spring temperatures. It is not clear, however,
      how long-distance migratory birds that overwinter thousands of kilometers to the
      south in the tropics cue into changes in temperature or plant phenology on
      northern breeding areas. We explored the relationships between the timing and
      rate of spring migration of long-distance migratory birds, and variables such as
      temperature, the North Atlantic Oscillation (NAO) and plant phenology, using mist
      net capture data from three ringing stations in North America over a 40-year
      period. Mean April/May temperatures in eastern North America varied over a 5
      degrees C range, but with no significant trend during this period. Similarly, we
      found few significant trends toward earlier median capture dates of birds. Median
      capture dates were not related to the NAO, but were inversely correlated to
      spring temperatures for almost all species. For every 1 degrees C increase in
      spring temperature, median capture dates of migratory birds averaged, across
      species, one day earlier. Lilac (Syringa vulgaris) budburst, however, averaged 3
      days earlier for every 1 degrees C increase in spring temperature, suggesting
      that the impact of temperature on plant phenology is three times greater than on
      bird phenology. To address whether migratory birds adjust their rate of northward
      migration to changes in temperature, we compared median capture dates for 15
      species between a ringing station on the Gulf Coast of Louisiana in the southern
      USA with two stations approximately 2,500 km to the north. The interval between
      median capture dates in Louisiana and at the other two ringing stations was
      inversely correlated with temperature, with an average interval of 22 days, that
      decreased by 0.8 days per 1 degrees C increase in temperature. Our results
      suggest that, although the onset of migration may be determined endogenously, the
      timing of migration is flexible and can be adjusted in response to variation in
      weather and/or phenology along migration routes.

PMID- 15480802
TI  - What limits herb biomass in grasslands: competition or herbivory?
AB  - Competition and herbivory are two of the main forces shaping plant communities.
      Although several studies have investigated their impact on plant populations
      separately, few investigations have examined how they might interact. With the
      purpose of clarifying the combined roles of competition and herbivory on herb
      biomass in a grassland, we assessed the effects of different herbivores with
      reduced grass competition. We conducted a field experiment in 2000-2001 in a
      British acid grassland (Oak Mead), where we experimentally reduced grass biomass
      and excluded rabbits, insects and molluscs in a factorial design. Removing the
      grasses from Oak Mead dramatically increased herb biomass and total above-ground
      biomass. Herbivore exclusions (i.e. rabbits, insects and molluscs) did not affect
      total above-ground biomass, but they altered relative abundance of several
      species. Grass removal and rabbit exclusion had positive interactions on biomass
      of several herb species, and there were some subtle interactions between
      different herbivore groups: monocots benefitted when both rabbits and molluscs
      were excluded, and some herb species had greater biomass when insects and rabbits
      were absent. We then compared the results with a 10-year experiment that
      manipulated similar variables in neighbouring grassland (Nash's Field). The
      comparison between Oak Mead and Nash's Field showed that cessation of herbicide
      application returns the system to its previous state of grass dominance after 3
      years. Therefore, even when herbs were more abundant, they could not prevent
      reinvasion of the grasses once external factors were removed.

PMID- 15480803
TI  - Predation by sparrowhawks decreases with increased breeding density in a
      songbird, the great tit.
AB  - Predators may regulate prey populations if predation rate increases with prey
      density. Alternatively, if space-limited (e.g. territorial) predators become
      'satiated' when prey exceed a certain density, increased prey abundance may lead
      to reduced predation rate. These alternatives have been difficult to test
      experimentally for mobile prey in the wild. We present such a test, manipulating
      the density of great tits (Parus major) by adding nest boxes in territories of
      sparrowhawks (Accipiter nisus). Predation rate was measured for young tits after
      they left the nests. Although the great tit is an important prey, there was no
      evidence for regulation during the breeding season: the rate of hawk predation
      declined with increasing density of tits. This result was not confounded by
      changes in breeding density of alternative prey species (other songbirds). Hawk
      predation can therefore favour dense breeding in a territorial (solitary) bird,
      and conspecific attraction and aggregation reported in several territorial
      species may partly result from predation pressure. This result also has potential
      implications for conservation work.

PMID- 15480804
TI  - Growth and reproduction of the alpine grasshopper Miramella alpina feeding on CO2
      enriched dwarf shrubs at treeline.
AB  - The consequences for plant-insect interactions of atmospheric changes in alpine
      ecosystems are not well understood. Here, we tested the effects of elevated CO(2)
      on leaf quality in two dwarf shrub species (Vaccinium myrtillus and V.
      uliginosum) and the response of the alpine grasshopper (Miramella alpina) feeding
      on these plants in a field experiment at the alpine treeline (2,180 m a.s.l.) in
      Davos, Switzerland. Relative growth rates (RGR) of M. alpina nymphs were lower
      when they were feeding on V. myrtillus compared to V. uliginosum, and were
      affected by elevated CO(2) depending on plant species and nymph developmental
      stage. Changes in RGR correlated with CO(2)-induced changes in leaf water,
      nitrogen, and starch concentrations. Elevated CO(2) resulted in reduced female
      adult weight irrespective of plant species, and prolonged development time on V.
      uliginosum only, but there were no significant differences in nymphal mortality.
      Newly molted adults of M. alpina produced lighter eggs and less secretion
      (serving as egg protection) under elevated CO(2). When grasshoppers had a choice
      among four different plant species grown either under ambient or elevated CO(2),
      V. myrtillus and V. uliginosum consumption increased under elevated CO(2) in
      females while it decreased in males compared to ambient CO(2)-grown leaves. Our
      findings suggest that rising atmospheric CO(2) distinctly affects leaf chemistry
      in two important dwarf shrub species at the alpine treeline, leading to changes
      in feeding behavior, growth, and reproduction of the most important insect
      herbivore in this system. Changes in plant-grasshopper interactions might have
      significant long-term impacts on herbivore pressure, community dynamics and
      ecosystem stability in the alpine treeline ecotone.

PMID- 15480805
TI  - Copepod and microzooplankton grazing in mesocosms fertilised with different Si:N
      ratios: no overlap between food spectra and Si:N influence on zooplankton trophic
      level.
AB  - We hypothesized that the trophic level of marine copepods should depend on the
      composition of the protist community. To test this hypothesis, we manipulated the
      phytoplankton composition in mesocosms and measured grazing rates of copepods and
      mesozooplankton in those mesocosms. Twelve mesocosms with Northeast Atlantic
      phytoplankton were fertilised with different Si:N ratios from 0:1 to 1:1. After 1
      week, ten of the mesocosms were filled with natural densities of mesozooplankton,
      mainly calanoid copepods, while two remained as mesozooplankton-free controls.
      Both before and after the addition of copepods there was a positive correlation
      of diatom dominance with Si:N ratios. During the second phase of the experiment,
      copepod and microzooplankton grazing rates on different phytoplankton species
      were assessed by a modification of the Landry-Hassett dilution technique, where
      the bottles containing the different dilution treatments were replaced by
      dialysis bags incubated in situ. The results indicated no overlap in the food
      spectrum of microzooplankton (mainly ciliates) and copepods. Ciliates fed on
      nanoplankton, while copepods fed on large or chain-forming diatoms, naked
      dinoflagellates, and ciliates. The calculated trophic level of copepods showed a
      significantly negative but weak correlation with Si:N ratios. The strength of
      this response was strongly dependent on the trophic levels assumed for ciliates
      and mixotrophic dinoflagellates.

PMID- 15480807
TI  - Antibiotic purification from fermentation broths by counter-current
      chromatography: analysis of product purity and yield trade-offs.
AB  - Counter-current chromatography (CCC) is a low pressure, liquid-liquid
      chromatographic technique which has proven to be a powerful purification tool for
      the high-resolution fractionation of a variety of active pharmaceutical
      compounds. The successful integration of CCC into either existing or new
      manufacturing processes requires the predictable purification of target compounds
      from crude, fermentation-derived, feed streams. This work examines the
      feasibility of CCC for the purification of fermentation-derived erythromycin A
      (EA) from its structurally and chemically similar analogues. At the laboratory
      scale, the effect of feed pre-treatment using either clarified, forward extracted
      (butyl acetate) or back extracted broth on EA separation was investigated. This
      defined the degree of impurity removal required, i.e. back extracted broth, to
      ensure a reproducible elution profile of EA during CCC. Optimisation and scale-up
      of the separation studied the effects of mobile phase flow (2-40 ml.min(-1)) and
      solute loading (0.1-10 g) on the attainable EA purity and yield. The results in
      all cases demonstrated a high attainable EA purity (>97% w/w) with throughputs up
      to 0.33 kg.day(-1). Secondly, a predictive scale-up model was applied
      demonstrating, that from knowledge of the solute distribution ratio of EA (K(EA))
      at the laboratory scale, the EA elution time at the pilot scale could be
      predicted to within 3-10%, depending upon the solute injection volume. In
      addition, this study has evaluated a "fractionation diagram" approach to visually
      determine the effects of key operational variables on separation performance.
      This resulted in accurate fraction cut-point determination for a required degree
      of product purity and yield. Overall, the results show CCC to be a predictable
      and scaleable separation technique capable of handling real feed streams.

PMID- 15480808
TI  - Optimal operation of high-pressure homogenization for intracellular product
      recovery.
AB  - An optimal control methodology for the homogenization of bacterial cells to
      recover intracellular products is presented. A Fluent computational fluid
      dynamics (CFD) model is used to quantify the hydrodynamic forces present in the
      homogenizer, and empirical models are used to relate these forces to
      experimentally obtained cell disruption and product recovery data. The optimal
      homogenizer operation, in terms of either constant cell breakage or maximum
      intracellular product recovery, is determined using these empirical models. We
      illustrate this methodology with an Escherichia coli bacterial system used to
      produce DNA plasmids. Homogenization is performed using an industrial APV-Gaulin
      high-pressure homogenizer. The modeling and optimization results for this E. coli
      DNA plasmid system show good agreement with the experimental data.

PMID- 15480809
TI  - Optimising nutrition in chronic renal insufficiency--growth.
AB  - The need to optimise nutrition to promote growth in infants with chronic renal
      insufficiency (CRI) is well recognised, but there is less enthusiasm for such an
      approach in older children and those with milder degrees of CRI. Energy intakes
      and growth outcomes were prospectively monitored over a 2-year period in children
      aged 2-16 years with differing levels of severity of CRI, as part of their
      ongoing joint medical/ dietetic care. Children were grouped following [(51)Cr]
      labelled EDTA glomerular filtration rate (GFR, ml/min per 1.73 m(2)) estimations,
      into 'normal' kidney function [GFR >75, mean 106 (SD 19.5), n =58], providing
      baseline data only, mild (GFR 51-75, n =25), moderate (GFR 25-50, n =21), and
      severe (GFR <25, n=19) CRI. Children were followed for 2 years, with 51
      completing the study (19 mild, 19 moderate, 13 severe CRI), and were excluded if
      they required dialysis. None received growth hormone. Regular dietary advice was
      provided and yearly 3-day semi-quantitative dietary diaries and baseline and 6
      monthly anthropometric measurements were obtained. Mean height standard deviation
      score (SDS) was maintained in those with mild and moderate CRI and significantly
      increased in children with severe CRI [0.1 SDS (0.32 SD), F =9.45, 1 df, P
      =0.003]. There was a non-significant reduction in energy intake from dietary
      records overall (median -8.5% estimated average requirement), associated with
      poor adherence to supplements in severe CRI and under-reporting in the mild
      group. An increase in height or body mass index SDS, however, was observed in all
      children who took the supplements as prescribed. A correlation between change in
      energy intake and change in height SDS was observed in severe CRI ( r(2)=0.58, P
      =0.011). Regular dietetic advice, with particular attention to adherence to
      optimise energy intake, may improve growth, irrespective of age and should form
      an integral part of the clinical care package.

PMID- 15480810
TI  - Stories from doctors of patients with pain. A qualitative research on the
      physicians' perspective.
AB  - GOAL OF WORK: The aim of this study was to explore the physicians' internal
      representation of the doctor-patient relationship in the dramatic field of the
      patient with pain. METHODS: Using an open narrative format, 151 physicians were
      asked to "Tell us about an episode during your professional experience in which
      you found yourself in difficulty whilst confronting a patient who was in pain".
      The narrations were examined in accordance with a clinical-interpretive method.
      MAIN RESULTS: Three "perspectives of observation" were identified, namely: the
      biological perspective, the professional perspective, and the personal
      perspective. The biological perspective is about the biological model and the
      "depersonalization" of pain. In the professional perspective, the narrative
      concerns the patient as a "person" and the reattribution of the pain to the
      suffering person. The personal perspective is about the emotional-relational
      explosion within the meeting between the doctor as human being and the patient as
      human being. Most of the narrations did not strictly connect to one or another of
      the perspectives, but each story seemed a journey without peace back and forth
      among the perspectives. CONCLUSIONS: The professional perspective seemed to be
      the only place in which physicians could "stop", a space not extreme in which
      they seemed to express the need for education about the management of the
      professional relationship with the other person.

PMID- 15480811
TI  - Gaps and junctions between clinical experience and theoretical framework in the
      use of opioids.

PMID- 15480812
TI  - Antiemetic therapy for multiple-day chemotherapy and high-dose chemotherapy with
      stem cell transplant: review and consensus statement.
AB  - The objective of this paper is to evaluate the efficacy of modern antiemetic
      therapy for chemotherapy-induced nausea and vomiting for patients receiving
      multiple-day or high-dose chemotherapy. Published phase II and phase III studies
      as well as their personal experiences were evaluated by the authors to develop
      this consensus statement. The largest published experience with multiple-day
      chemotherapy is with 5-day cisplatin combination chemotherapy. The introduction
      of 5-HT3 antagonists greatly improved emetic control. However, day 4-5 nausea as
      well as delayed nausea and vomiting remains a clinical problem despite the
      inclusion of dexamethasone. A 5-HT3 antagonist plus dexamethasone is the
      preferred current option for patients receiving high-dose chemotherapy with stem
      cell transplant. However, the results do not appear as successful as for highly
      emetic standard-dose chemotherapy.

PMID- 15480813
TI  - The Hospital Anxiety and Depression Scale in Greek cancer patients: psychometric
      analyses and applicability.
AB  - GOALS OF WORK: The aim of the present study was to validate the Greek version of
      the Hospital Anxiety and Depression Scale (HAD) in a palliative care unit.
      PATIENTS AND METHODS: The scale was translated with the "forward-backward"
      procedure to Greek. It was administered twice, with a 1-week interval, to 120
      patients with advanced cancer. Together with the HAD scale, the patients also
      completed the Spielberger State-Anxiety Scale (STAI-S). MAIN RESULTS: Factor
      analyses identified a two-factor solution corresponding to the original two
      subscales of the HAD, which were found to be correlated. The Greek version of the
      HAD had Cronbach's alphas for the anxiety and depression scales of 0.887 and
      0.703, respectively. Validity as performed using known-group analysis showed good
      results. Both anxiety and depression subscales discriminated well between
      subgroups of patients differing in disease severity as defined by ECOG
      performance status. Correlations between the HAD scale and the STAI-S was 0.681
      for the anxiety subscale and 0.485 for the depression subscale. CONCLUSIONS:
      These psychometric properties of the Greek version of the HAD scale confirm it as
      a valid and reliable measure when administered to patients with advanced cancer.

PMID- 15480814
TI  - Donepezil and vitamin E for preventing cognitive dysfunction in small cell lung
      cancer patients: preliminary results and suggestions for future study designs.
AB  - BACKGROUND: Up to 90% of small cell lung cancer (SCLC) patients suffer cognitive
      dysfunction. Since donepezil and vitamin E have been somewhat successful in
      treating other dementias, this study tested the hypothesis that these agents can
      prevent cognitive decline in SCLC patients. Because accrual was poor, this trial
      also offered opportunities for suggesting other study designs for future clinical
      trials on cognitive dysfunction in this group of patients. METHODS: This double
      blind, placebo controlled trial tested oral donepezil 5 mg/day (with dose
      escalation to 10 mg after 1 month) and oral vitamin E 1,000 IU/day in SCLC
      patients after completion of all cancer therapy, including prophylactic cranial
      irradiation (PCI). Cognition, adverse events, and quality of life were assessed
      throughout the study period. RESULTS: Only nine of 104 patients enrolled over 15
      months (four donepezil and vitamin E-treated versus five placebo-exposed), and
      thus no definitive conclusions could be drawn. Nonetheless, the only patient who
      manifested a precipitous decline in cognition was taking donepezil and vitamin E.
      There was also a slight trend of increased gastrointestinal side effects among
      donepezil and vitamin E-treated patients. There were no notable differences in
      cognitive stability, adverse events, or quality of life between treatment arms.
      CONCLUSION: These preliminary findings do not provide enthusiasm for testing
      donepezil and vitamin E in the manner undertaken here for preventing cognitive
      dysfunction in SCLC patients. Eligibility criteria and timing of trial
      intervention are discussed as potential impediments to successful trial
      completion.

PMID- 15480815
TI  - Treatment of cancer-related pain with transdermal buprenorphine: a report of
      three cases.
AB  - Three patients suffering from pain arising from renal and metastasing prostate
      and breast cancer were successfully treated with transdermal buprenorphine. The
      three cases demonstrate that transdermal buprenorphine is an easy-to-use and
      effective therapeutic option for the treatment of advanced cancer pain, that it
      can also be used in opioid rotation as an alternative after formerly applied
      steps II or III opioids have failed and that long-term treatment without dose
      escalation or compromise in tolerability is possible.

PMID- 15480816
TI  - Depressive symptom patterns and their consequences for diagnosis of affective
      disorders in cancer patients.
AB  - GOALS OF WORK: In order to obtain references for adequate diagnostic procedures
      of depressive syndromes in cancer patients, the present study analyzes first the
      prevalence of somatic, emotional, and cognitive symptoms of depression. In a
      second part, the ability of diagnostic procedures to discriminate between
      patients with and without comorbid affective disorder is investigated. PATIENTS
      AND METHODS: From a cross-sectional survey investigating comorbid mental
      disorders in cancer patients with standardized clinical assessment, a subsample
      of 71 patients with current affective disorders and depressive symptoms according
      to the Diagnostic and Statistic Manual of Mental Disorders, 4th edition (DSM-IV)
      were analyzed. In addition to patients' symptom patterns, a discriminant analysis
      including all depressive symptoms was conducted. MAIN RESULTS: Cognitive symptoms
      are less prevalent in cancer patients than somatic and emotional symptoms. Loss
      of interest discriminated best between patients with and without diagnosis of
      comorbid affective disorder. Additionally, decreased energy and fatigue proved to
      have discriminatory value. CONCLUSIONS: Cognitive symptoms should receive special
      attention in diagnostic procedures for affective disorders in cancer patients. In
      spite of possible symptom overlap with the cancer disease and its treatment,
      fatigue proves to be a useful criteria for diagnosis of depression.

PMID- 15480817
TI  - Pain intensity assessment by bedside nurses and palliative care consultants: a
      retrospective study.
AB  - OBJECTIVE: To evaluate the specificity, sensitivity, and accuracy of pain
      intensity assessments (0-10) conducted by registered nurses (RN) and clinical
      nurse assistants (CAN) as compared to those conducted by the palliative care
      consultant (PCC). PATIENTS AND METHODS: We performed a retrospective review of
      charts of patients who had received palliative care consult between April 2002
      and August 2002. Data on patient demographic, date of palliative care consult,
      and date and intensity of pain assessment were collected. A numerical rating
      scale from 0 (no pain) to 10 (worst pain) was used to assess pain intensity. The
      data were included for analysis if the pain intensity assessment was performed
      during the same shift by all three care providers (RN, CNA, and PCC). RESULTS:
      Forty-one charts were found to include a complete pain assessment performed by
      the RN, CNA, and PCC. The agreement of pain intensity between the PCC and both
      the RN and CNA was poor. For a diagnosis of moderate-to-severe pain, the RN's
      intensity assessment had a specificity of 90% but a sensitivity of 45%, and the
      CNA's intensity assessment had a specificity of 100% but a sensitivity of only
      30%. The Spearman correlation coefficient between the intensity assessments
      performed by the PCC and the RN was 0.56 (p=0.00) and between those by the PCC
      and the CNA 0.22 (p=0.15). CONCLUSION: Lack of agreement between pain intensity
      assessments performed by the PCC and bedside nurse suggests possible
      inconsistencies in the way the assessments were performed. Better education on
      how to perform standard pain intensity assessment is needed.

PMID- 15480818
TI  - Pain evaluation and management: a survey of Italian radiotherapists.
AB  - GOALS: The objective of this study was to assess the knowledge possessed and the
      attitudes held by Italian radiotherapists regarding evaluation and treatment of
      pain. METHODS: One hundred and twenty-six radiotherapists completed a 16-item
      questionnaire that was specifically designed to investigate three main topics:
      the attention paid to pain, the use of analgesics, and pain in children. Chi
      square or Fisher's exact text was employed to evaluate differences based on
      position (staff/resident), age (<35 or >35 years old), availability of
      consultants in pain therapy and/or palliative care, colleagues with main interest
      in palliative care among their own staff, and region of residence
      (north/center/south of Italy). RESULTS: Overall percentage of correct answers was
      76.6% (range 34.9-94.4%). Correct answers by groups of items were: attention paid
      to pain 77.3%, use of analgesics 81.5%, and pain in children 63.7%. CONCLUSION:
      Results of the survey demonstrate that knowledge and attitudes of Italian
      radiotherapists towards the approach to and treatment of pain can be considered
      satisfactory.

PMID- 15480819
TI  - Administration of recombinant human erythropoietin alpha before autologous stem
      cell transplantation reduces transfusion requirement in multiple myeloma
      patients.
AB  - Recombinant human erythropoietin administered after peripheral blood stem cell
      transplantation (PBSCT) has been ineffective for the treatment of anemia. We
      administered recombinant human erythropoietin alpha (rHuEPO) prior to high-dose
      therapy after peripheral blood stem cell (PBSC) collection to evaluate its
      efficacy on transfusion requirements and hematological parameters during the post
      transplant aplastic phase. Twenty-two multiple myeloma patients (EPO-MM) were
      included in the trial to receive rHuEPO 10,000 IU subcutaneous daily starting 30
      days before PBSCT. Forty hemoglobin (Hb)-matched patients who had not received
      rHuEPO before transplant were retrospectively selected (Ctr-MM) for comparative
      data. None of the patients received transfusions at study entry. All but one
      patient responded to rHuEPO. However, no significant differences in Hb levels
      were obtained between the two groups at the time of transplantation. At nadir,
      the EPO-MM cases had a significantly higher Hb level (median 10 g/dl versus 7.6
      g/d; p=0.001). Consequently, less than 20% of EPO-MM patients required packed red
      blood cell (PRBC) transfusions compared to more than half the Ctr-MM patients
      (p=0.007). Furthermore, the number of PRBC transfusions performed in the EPO-MM
      group was significantly lower (median 0 versus 1; p=0.008). Independently of Hb
      levels at PBSCT, rHuEPO therapy was significantly associated with a lower risk of
      transfusion requirement. In conclusion, rHuEPO is shown to be effective when
      administered prior to high-dose therapy in MM.

PMID- 15480820
TI  - Successful use of ketamine for intractable cancer pain.
AB  - GOALS AND WORK: Despite medical awareness, intractable pain is a serious problem
      in cancer and occurs in up to 2% of advanced cancer patients. However, few data
      are available concerning the optimal treatment of such patients. The emergence of
      intractable pain may notably be due to the activation of N-methyl-D-aspartate
      (NMDA) receptors located in the central nervous system. NMDA antagonists might
      thus be an interesting approach in such pain syndromes. PATIENTS AND METHODS:
      Twelve patients with intractable cancer pain received a test dose of 5-10 mg of
      ketamine, a strong NMDA antagonist, in order to determine their response and
      tolerance to the drug. Continuous intravenous infusions of ketamine associated
      with morphine were then administered. MAIN RESULTS: The acute test dose was
      successful in all cases (VAS <3/10 after 5 min). The prolonged use of ketamine
      allowed us to reduce the total daily dose of morphine required (range: 200-1,200
      mg) by 50% and allowed eight patients to go home with a portable pump with
      morphine and ketamine during a relatively long period of time (range: 7-350 days,
      median: 58 days). Side effects were moderate (dizziness) and they were limited to
      the test phase. CONCLUSION: Our data suggest the importance of NMDA receptors in
      the genesis of chronic cancer pain and indicate that NMDA antagonists should be
      further studied for the management of cancer pain and, in particular, intractable
      pain.

PMID- 15480822
TI  - Research and evidence about blood sparing in spine surgery.

PMID- 15480824
TI  - The use of local agents: Surgicel and Surgifoam.
AB  - There are various electrical, mechanical and chemical methods used to achieve
      haemostasis in spine surgery. Chemical haemostatic agents are often preferable to
      bipolar cautery in intraspinal procedures, because these products control
      bleeding without occluding the vessel lumen and cause no thermal injuries to
      adjacent structures. A topical haemostat is the often the technique of choice to
      control bleeding from bone and to diffuse capillary and epidural venous oozing.
      This paper focuses on technical aspects of the application of absorbable porcine
      gelatine and regenerated, oxidised cellulose. These haemostats have been used in
      neurosurgical intraspinal procedures for more than 30 years; however, new
      application forms like Surgicel fibrillar and Surgifoam powder imply different
      handling options, which are discussed in this paper.

PMID- 15480823
TI  - An overview of blood-sparing techniques used in spine surgery during the
      perioperative period.
AB  - The problems linked to blood loss and blood-sparing techniques in spine surgery
      have been less studied than in other fields of orthopedics, such as joint
      replacement procedures. Decreasing bleeding is not only important for keeping the
      patient's hemodynamic equilibrium but also for allowing a better view of the
      surgical field. In spine surgery the latter aspect is especially important
      because of the vicinity of major and highly fragile neurologic structures. The
      techniques and agents used for hemostasis and blood sparing in spinal procedures
      are mostly similar to those used elsewhere in surgery. Their use is modulated by
      the specific aspects of spinal approach and its relation to the contents of the
      spinal canal. Blood-sparing techniques can be divided into two categories based
      on their goals: either they are aimed at decreasing the bleeding itself, or they
      are aimed at decreasing the need for homologous transfusion. Various hemodynamic
      techniques, as well as systemic and local drugs and agents, can be used
      separately or in combination, and their use in the field of spine surgery is
      reported. The level of evidence for the efficacy of many of those methods in
      surgery as a whole is limited, and there is a lack of evidence for most of them
      in spine surgery. However, several blood-saving procedures and drugs, as well as
      promising new agents, appear to be efficient, although their efficacy has yet to
      be assessed by proper randomized controlled trials.

PMID- 15480825
TI  - Isolated thoracic spine lesion: is this the presentation of a SAPHO syndrome? A
      case report.
AB  - A case of an isolated lesion of the thoracic spine attributed to SAPHO syndrome
      is presented. A 51-year-old man was referred for inflammatory pain in the
      thoracic spine. The general examination was normal (especially cutaneous and
      rheumatologic examinations). Laboratory analysis showed only a mild inflammatory
      reaction. Standard radiographs showed partial condensation of T8. Computed
      tomography showed osteolysis of the anterior corner of T8, and MRI revealed an
      abnormal signal of T8, with enlargement of the prevertebral soft tissue.
      Percutaneous and thoracoscopic biopsies showed a nonspecific inflammatory
      process, and cultures were sterile. Initially, several diagnoses were advanced:
      infectious spondylitis, malignant tumor, lymphomas, Paget disease, seronegative
      spondyloarthropathies and finally atypical SAPHO syndrome. Three months later,
      the patient experienced more pain. General examination was still normal. The
      radiological findings worsened, while the inflammatory blood tests were normal. A
      new thoracoscopic biopsy revealed a nonspecific inflammatory process. A diagnosis
      of SAPHO syndrome was made, despite the lack of typical lesions. Dramatically
      improving with anti-inflammatory therapy, the patient's condition was favorable
      at 3-year follow-up. This atypical presentation of an isolated lesion in the
      spine makes the diagnosis of a SAPHO syndrome difficult but possible. Spine
      surgeons must be aware of this rare entity, to avoid misdiagnosis and unnecessary
      repeated surgical biopsies.

PMID- 15480826
TI  - Visualisation of the brace effect on the spinal profile in idiopathic scoliosis.
AB  - We studied the brace effect on the spinal profile in idiopathic scoliosis, using
      a MR procedure visualising the complete scoliotic spine in any vertical plane,
      while rotating it 180 degrees on the longitudinal axis of the patient. Thirty
      eight female patients (mean age, 14.5 years) were included in the study.
      Inclusion criteria were an idiopathic scoliosis, a Cobb angle greater than 20
      degrees , age of 10-17 years and bracing with a Cheneau brace. The brace effect
      was studied in 38 thoracic curves. The MR examinations were carried out in direct
      sequences, with and without brace. A reconstruction algorithm allows visualising
      the whole spine in vertical projections, with rotational steps of 2 degrees ,
      from -90 degrees to 90 degrees , referred to as MR animation. In various vertical
      MR projections, the changes of the curves were evaluated by measuring the Cobb
      angle. Additionally, a translation angle of the apical vertebra was determined,
      representing the lateral deviation of the apical vertebra from a defined midline.
      Testing the reproducibility of the Cobb angles, the standard deviation of the
      intra-individual differences was 1.7 degrees and of the inter-individual
      differences, 2.1 degrees . For the translation angles, the standard deviation of
      the intra-individual differences was 0.8 degrees and of the inter-individual
      differences, 0.9 degrees . With brace the mean Cobb angle of the thoracic curves
      was significantly reduced in the various vertical MR projections. The mean
      translation angle was also reduced. MR analysis showed that the brace effect is a
      translation process, straightening the profile of the scoliotic spine in all
      vertical planes. MR animation allows visualising the brace effect on the spine in
      scoliosis based on a 3D data set, without additional radiation exposure. It
      showed the straightening effect of the brace leading to a flattening of the
      sagittal spinal profile.

PMID- 15480827
TI  - Balloon kyphoplasty for the treatment of pathological vertebral compressive
      fractures.
AB  - BACKGROUND: Previous clinical studies have shown the safety and effectiveness of
      balloon kyphoplasty in the treatment of pathological vertebral compression
      fractures (VCFs). However, they have not dealt with the impact of relatively
      common comorbid conditions in this age group, such as spinal stenosis, and they
      have not explicitly addressed the use of imaging as a prognostic indicator for
      the restoration of vertebral body height. Neither have these studies dealt with
      management and technical problems related to surgery, nor the effectiveness of
      bone biopsy during the same surgical procedure. This is a prospective study
      comparing preoperative and postoperative vertebral body heights, kyphotic
      deformities, pain intensity (using visual analogue scale) and quality of life
      (Oswestry disability questionnaire) in patients with osteoporotic vertebral
      compression fractures (OVCFs) and osteolytic vertebral tumors treated with
      balloon kyphoplasty. METHODS: Thirty-two consecutive patients, 27 OVCFs (49
      vertebral bodies [VBs]) and 5 patients suffering from VB tumor (12 VBs) were
      treated by balloon kyphoplasty. The mean age was 68.2 years. All patients were
      assessed within the first week of surgery, and then followed up after one, three
      and six months; all patients (27 OVCFs and 5 tumor patients) were followed up for
      12 months, 17 patients (14 OVCFs and 3 tumors) were followed up for 18 months and
      9 patients (8 OVCFs and 1 tumor) were followed up for 24 months (mean follow up
      18 months). The correction of kyphosis and vertebral heights were measured by
      comparing preoperative and postoperative radiographic measurements. RESULTS:
      Thirty-one patients (96.9%) exhibited significant and immediate pain improvement:
      90% responded within 24 h and 6.3% responded within 5 days. Daily activities
      improved by 53% on the Oswestry scale. In the OVCF group, kyphosis correction was
      achieved in 24/27 patients (89.6%) with a mean correction of 7.6 degrees .
      Anterior wall height was restored in 43/49 VBs (88%) (mean increment of 4.3 mm),
      and mid vertebral body height was restored in 45/49 VBs (92%) (mean increment of
      4.8 mm). Edema (high intensity signal) on short tau inversion recovery (STIR) was
      evidenced in all OVCF patients who experienced symptoms for less than nine months
      and was associated with correction of deformity. Cement leakage was the only
      technical problem encountered; it occurred in 5/49 VBs (10.2%) of the
      osteoporotic group and 1/12 VBs (8.3%) of the tumor group but had no clinical
      consequences. The incidence of leakage to the anterior epidural space was 2%.
      Spinal stenosis was present in three patients (11.1%) who responded successfully
      to subsequent laminectomy. Retrieval of tissue samples for biopsy was successful
      in 10/15 cases (67%). New fractures occurred in the adjacent level in 2/27 OVCF
      patients (7.4%). CONCLUSIONS: Associated spinal stenosis with OVCF should not be
      overlooked; STIR MRI is a good predictor of deformity correction with balloon
      kyphoplasty. The prevalence of a new OVCF in the adjacent level is low.

PMID- 15480828
TI  - Biofidelic whole cervical spine model with muscle force replication for whiplash
      simulation.
AB  - Whiplash has been simulated using volunteers, whole cadavers, mathematical
      models, anthropometric test dummies, and whole cervical spines. Many previous in
      vitro whiplash models lack dynamic biofidelity. The goals of this study were to
      (1) develop a new dynamic whole cervical spine whiplash model that will
      incorporate anterior, lateral and posterior muscle force replication, (2)
      evaluate its performance experimentally and (3) compare the results with in vivo
      data. To evaluate the new model, rear-impact whiplash simulations were performed
      using the incremental trauma approach at maximum measured T1 horizontal
      accelerations of 3.6 g, 4.7 g, 6.6 g, and 7.9 g. The kinematic response of the
      new model, e.g., peak head-T1 extension and peak intervertebral rotations, were
      compared with the corresponding in vivo data. The average peak head-T1 extension
      was within the in vivo corridor during the 3.6 g whiplash simulation (9.1 kph
      delta V). The peak in vivo intervertebral rotations obtained during a 4.6 g
      whiplash simulation of a young volunteer were within, or only marginally in
      excess of, the 95% confidence limits of the average peak intervertebral rotations
      measured during the 4.7 g whiplash simulation of the present study. Thus, the new
      whole cervical spine model with muscle force replication produced biofidelic
      dynamic responses to simulated whiplash. The new model is capable of generating
      important biomechanical data that may help improve our understanding of whiplash
      injuries and injury mechanisms.

PMID- 15480829
TI  - Nasopharynx paraganglioma with extension in the clivus.
AB  - Paraganglioma is a rare benign tumor arising from the sympathetic nervous system.
      Here we describe an exceptional case of a paraganglioma located in the
      nasopharynx with an extension through the clivus up to the dura. Atypically, no
      contact with any major vessels was found. A radical resection of the mass was
      performed by an anterior transmaxillary approach through a Le Fort I osteotomy.
      One year follow up reveals no signs of local or distant recurrence. No cosmetic
      changes can be observed after the surgery and nasal and masticatory functions are
      unmodified. We review the clinical presentation, workup of paraganglioma, as well
      as the surgical approaches to the clivus.

PMID- 15480830
TI  - Multiregional sampling reveals a homogenous distribution of Ki-67 proliferation
      rate in pituitary adenomas.
AB  - Ki-67 antigen is used as a marker of proliferative activity that is linked to
      growth rate, invasiveness and prognosis of pituitary adenomas. So far the
      distribution of Ki-67 index within an individual adenoma has not been
      investigated. If Ki-67 antigen expression differs significantly within an
      individual pituitary adenoma, a sampling error may result when assessing small
      fragments of adenoma tissue. Such a potential error would diminish the value of
      Ki-67 as a tool for postoperative patient management considerations. The aim of
      the present study was to assess Ki-67 proliferation rates in different regions of
      pituitary adenomas and to statistically analyse these data for potential regional
      differences within each tumor. Ki-67 proliferation index was assessed in smear
      preparations of 100 specimens of 26 consecutive patients operated on for
      pituitary adenoma in the Department of Neurosurgery, Medical University Vienna.
      Depending on the size and extent of the tumor, a mean of 4 tissue samples (range
      2-8) was selected intraoperatively from each adenoma from endosellar,
      suprasellar, parasellar, and basal sellar dural locations. Overall mean cell
      proliferation rate measured by Ki-67 was 1.81 +/- 0.90% (range 0.33-3.43%).
      Histologically invasive adenomas had significantly higher mean Ki-67
      proliferation index in all samples from the same tumor than non-invasive adenomas
      (2.01 +/- 0.91% vs. 1.11 +/- 0.59%; P = 0.024). Multiregional sampling revealed a
      homogenous distribution of Ki-67 index throughout an individual adenoma with no
      significant differences between any two different regions on t-test. Our data
      confirm that location of a biopsy does not influence Ki-67 index. Therefore, Ki
      67 index of a single biopsy is representative for the whole individual adenoma.
      Thus Ki-67 index can be considered a reliable parameter for assessment of cell
      proliferation rate in adenoma biopsies and may be used for postoperative patient
      management considerations.

PMID- 15480831
TI  - Differential patterns of cognitive impairment in patients with aqueductal
      stenosis and normal pressure hydrocephalus.
AB  - METHODS: We report a preoperative neuropsychological evaluation for ten adult
      patients with aqueductal stenosis, and compare the results of this group with a
      normal pressure hydrocephalus group. FINDINGS: For executive functions,
      aqueductal stenosis patients failed on isolated tests and results were
      heterogeneous; the normal pressure hydrocephalus group was more impaired, except
      for tasks which required memory processing. Memory deficits in aqueductal
      stenosis group are qualitatively dissimilar and more homogeneous and severe,
      despite the younger age, than in the normal pressure hydrocephalus group.
      INTERPRETATION: These findings indicate that neuropsychological deficits of
      patients with aqueductal stenosis are linked with fornix damage and frontal
      dysfunction. In the normal pressure hydrocephalus group, deficits could be linked
      with a prefrontal lobe disconnection.

PMID- 15480832
TI  - Decompression of endocrine orbitopathy via an extended extradural pterional
      approach.
AB  - BACKGROUND: Numerous surgical decompression techniques have been described in
      endocrine orbitopathy. We present an overview of the treatment and clinical
      outcome of 13 patients with endocrine ophthalmopathy and 20 orbital
      decompressions via an extradural pterional approach, carried out in our center
      from 1995 to 2002. METHOD: Decompression of the antero- and posterolateral wall,
      of the roof, and the superior orbital fissure was performed in all cases.
      FINDINGS: Surgery reduced the degree of exophthalmos in all patients, and
      improved eye mobility and diplopia. Proptosis reduction at 3 months after surgery
      averaged 4.75 mm. A mean of 0.29 of better visual acuity was also achieved. There
      was no loss of visual acuity. Intra-ocular tension was reduced by 9.05 mm Hg on
      average. No diplopia was induced. INTERPRETATION: The pterional approach
      facilitates adequate proptosis reduction without inducing any double vision and
      allows adequate decompression of the orbital apex, and of the superior orbital
      fissure. This technique represents an effective and low-risk alternative to other
      techniques.

PMID- 15480833
TI  - A tribute for Prof. Dr. Melvin D. Yahr, M.D. (1917-2004).

PMID- 15480834
TI  - Ultrastructural localization of parkin in the rat brainstem, thalamus and basal
      ganglia.
AB  - The parkin gene encodes a 52 kd putative E3 ubiquitin-protein ligase involved in
      an autosomal recessive form of early onset parkinsonism. Parkin ultrastructural
      localization was studied by immunohistochemistry in the adult rat brain and in a
      parkin inducible PC12 cell line (HS22). In the rat brain, parkin immunoreactivity
      was detected in neuronal and glial cell bodies and in nerve processes. In the
      neurons, it was mostly localized on the periphery of large vesicles, some rare
      mitochondria and endoplasmic reticulum in the cell bodies, and on the periphery
      of large vesicles in the dendrites and terminals of the neurons. In addition,
      parkin immunoreactivity was also found around synaptic vesicles in the
      presynaptic elements of some axons. In HS22 cells over-expressing parkin, the
      distribution of the protein was similar to that observed in the perikarya of the
      labeled neurons.

PMID- 15480835
TI  - Lewy body-related alpha-synucleinopathy in the aged human brain.
AB  - To clarify the significance of Lewy body (LB)-related alpha-synucleinopathy in
      aging and various neurodegenerative disorders, its incidence and topographic
      pattern were examined in 260 brains of elderly patients, including 116 autopsy
      proven cases of Alzheimer disease (AD), 71 cases of clinically and autopsy-proven
      Parkinson disease (PD), 38 of dementia with Lewy bodies (DLB), 8 patients with
      progressive supranuclear palsy (PSP), one with senile tremor, and 26 age-matched
      controls without neuropsychiatric disorders. Using immunohistochemistry, alpha
      synuclein (AS) positive lesions were assessed semiquantitatively. For technical
      reasons, the olfactory system was not systematically studied. All PD-brains
      showed AS-positive lesions in medullary, pontine and mesencephalic nuclei, with
      involvement of the nucleus basalis (90.1%), limbic cortex (58.9%), cingulate
      cortex (46%), amygdala, CA 2/3 hippocampal region (36.2%), neocortex (28.8%), and
      striatum (11%). 88% of clinical PD cases corresponded to LB pathology stages 4-6,
      12% to stage 3 according to Braak et al. (2003). 84% of DLB brains were PD stage
      5 or 6 and 17% stage 4, without significant differences between DLB with and
      without neuritic AD pathology, suggesting morphologic similarities betwee these
      disorders. 6/8 PSP and senile tremor cases, 49.1% of AD and 69% of aged controls
      were negative. AS-positive lesions in AD showed decreasing incidence from
      midbrain (24-28%), limbic cortex and amygdala (17-18%), nucleus basalis and
      medullary nuclei (13-17%), cingulate cortex (12%), CA 2/3 region (8%) to
      neocortex (2%), without gender differences or relationship to the severity of AD
      pathology (mean Braak stage 5.1). AD cases with AS positive lesions, particularly
      those with AS pathology in the amygdala, were older at death than negative ones
      (86.6 vs 83.3 yrs), but this difference was not statistically significant. 15 AD
      cases (seven of them with mild PD symptoms) and 3 aged controls without
      parkinsonian signs but LB pathology stages 3 (n=5) and 4 (n=13) were considered
      "incidental LB disease". 16 AD brains without parkinsonian symptoms had AS
      positive lesions in various areas without medullary involvement, suggesting
      deviation from the proposed stereotypic expansion pattern. Located AS-pathology
      in the midbrain and limbic cortex was seen in 31% of asymptomatic aged controls.
      These data 1. largely confirm Braak's staging of LB-pathology in PD; 2. suggest
      morphologic and pathogenic relations between PD (brainstem type) and DLB with and
      without coexistent AD pathology; 3. the occurrence of LB-related alpha
      synucleinopathy in about 50% of AD brains and about 30% of aged controls.
      However, the basic mechanisms of LB-related AS-pathology and their pathogenic and
      clinical relevance in aged brain and neurodegenerative disorders await further
      elucidation.

PMID- 15480836
TI  - Inhibition of proteasome activity sensitizes dopamine neurons to protein
      alterations and oxidative stress.
AB  - Impairment in the capacity of the ubiquitin-proteasome pathway to clear unwanted
      proteins has been implicated in the cell death that occurs in Parkinson's disease
      (PD). In support of this concept, defects in proteasomal structure and function,
      as well as protein aggregates and increased levels of oxidized proteins are found
      in the substantia nigra of PD patients. We have previously demonstrated that
      inhibition of proteasome activity in mesencephalic cultures induces degeneration
      of dopaminergic neurons coupled with the formation of proteinaceous intracellular
      inclusions. In this study we examined the effect of proteasome inhibition on
      cultured dopamine neurons when combined with oxidative stress and protein
      misfolding, in order to better simulate the condition in PD. We demonstrate that
      two structurally unrelated inhibitors of proteasome activity, lactacystin and
      carbobenzoxy-L-leucul-L-leucyl-L-leucinal (MG132), cause dose-dependent cell loss
      that preferentially affects dopaminergic neurons. Conditions that promote protein
      damage and misfolding such as oxidative stress, heat shock, and canavanine also
      induce neuronal degeneration with preferential loss of dopamine neurons and cell
      death is markedly increased when any of these is combined with a proteasome
      inhibitor. These studies demonstrate a synergistic effect between conditions that
      promote the formation of damaged proteins and those in which proteasomal function
      is impaired, and provide further support for the notion that cell loss in PD
      could be related to a defect in protein handling.

PMID- 15480837
TI  - Neuromelanin inhibits enzymatic activity of 26S proteasome in human dopaminergic
      SH-SY5Y cells.
AB  - Recently, impairment of the ubiquitin-proteasome system is suggested to be
      responsible for the neuronal death in ageing and Parkinson's disease. The
      specific degeneration of dopamine neurons containing neuromelanin (NM) suggests
      that NM itself may be involved in the cellular dysfunction and death, even though
      the direct link has never been reported. We examined the effects of NM isolated
      from the human substantia nigra on the proteasome activity in human dopaminergic
      SH-SY5Y cells. NM reduced the activities of 26S proteasome, as shown in situ
      using a green fluorescent protein homologue targeted to 26S proteasome and also
      in vitro using ubiquitinated lysozyme as a substrate. However, NM did not affect
      20S proteasome activity in vitro. NM reduced the amount of PA700 regulatory
      subunit of 26S proteasome, but did not affect that of alpha- and beta-subunits of
      20S proteasome. These results suggest that NM may inhibit the ubiquitin-26S
      proteasome system, and determine the selective vulnerability of dopamine neurons
      in ageing and related disorders.

PMID- 15480838
TI  - Dopamine transporter: involvement in selective dopaminergic neurotoxicity and
      degeneration.
AB  - The carrier molecule that transports dopamine (DA) into dopamine neurons by an
      electrogenic, Na(+)- and Cl(-)-transport-coupled mechanism is known as the
      dopamine transporter (DAT). This uptake system is exclusively expressed in DA
      neurons with significantly higher levels of DAT expression in cells of the
      substantia nigra pars compacta than those of the ventral tegmental area and
      arcuate hypothalamic neurons. The expression density of DAT strongly correlates
      with the extent of DA cell loss in Parkinson's disease (PD). There are also DAT
      gene polymorphisms associated with PD. These data suggest a role of the DAT in
      the pathogenesis of PD. Though selective for its respective neurotransmitter, the
      DAT can also transport synthetic/natural analogues of the transmitter. Should
      such compounds interact with vital intracellular structures, their penetration
      into the neuron might have significant consequences. This sequence of toxic
      events could indeed demonstrated for the synthetic toxin 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP), which produces selective degeneration of DA
      neurons characteristic of PD. Dopaminergic toxicity of its active metabolite 1
      methyl-4-pyridinium (MPP(+)) is mediated by the DAT through accumulation into DA
      neurons, where it inhibits mitochondrial complex I activity. Various endogenous
      and exogenous heterocyclic molecules, which are structurally related to
      MPTP/MPP(+), such as isoquinolines and beta-carbolines, have been reported to
      exhibit similar toxic properties on DA cells, which are conferred by their uptake
      by the DAT. Taken together, there is large body of evidence from morphological,
      molecular biological and toxicological studies indicating that the DAT might be
      responsible for the selectivity of DA cell death in PD.

PMID- 15480839
TI  - Cognitive and behavioral dysfunction in Parkinson's disease: neurochemical and
      clinicopathological contributions.
AB  - The cognitive and behavioral sequelae (i.e., nonmotor profile) of Parkinson's
      disease (PD), with executive dysfunction and depression being most prominent,
      have typically been overshadowed due to an emphasis on motor symptomatology. The
      apparent categorization of PD as a disorder isolated to the dopaminergic system
      may be a generalization of the disease pathology. Dopamine therapy, used for the
      treatment of motor symptoms, has not consistently been shown to resolve nonmotor
      impairments. Research evidence indicates that nondopaminergic neurotransmitter
      systems (i.e., serotonergic, noradrenergic, & cholinergic) are disrupted in PD
      and may contribute to cognitive and behavioral dysfunction. Furthermore, Lewy
      bodies within cortical and subcortical structures can add to the nonmotor profile
      in PD. Pharmacological interventions for the treatment of cognitive and
      behavioral impairments associated with PD are few, especially for nondemented
      patients. The current review of the literature highlights evidence that
      associates nonmotor dysfunctions with neurochemical and clinicopathological
      correlates of PD.

PMID- 15480840
TI  - Cognitive dysfunction and dementia in Parkinson's disease.
AB  - Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder
      mainly characterized by degeneration of dopaminergic neurons in the substantia
      nigra and the ventral tegmental area, in combination with a varying loss of
      central noradrenergic (locus coeruleus), cholinergic (nucleus basalis of Meynert)
      and serotonergic (dorsal raphe nuclei) integrity, leading to a multitude of motor
      and non-motor behavioral disturbances. Apart from the clinical motor hallmarks,
      in the early stages of disease, subtle cognitive dysfunction might be seen
      comprising mainly executive dysfunction, with secondary visuospatial and mnemonic
      disturbances. In about 20-40% of patients, these problems may eventually proceed
      to dementia, which constitutes an important risk factor for caregiver distress,
      decreased quality of life and nursing home placement. Dementia in PD is typically
      characterized by a progressive dysexecutive syndrome with attentional deficits
      and fluctuating cognition, often accompanied by psychotic symptoms. It is thought
      to be the result of a combination of both subcortical and cortical changes. PD
      related dopaminergic deficiency in the nucleus caudatus and mesocortical areas
      (due to degeneration of projections from the substantia nigra and ventral
      tegmental area) and cholinergic deficiency in the cortex (due to degeneration of
      ascending projections from the nucleus basalis of Meynert), combined with
      additional Alzheimer-pathology and cortical Lewy bodies, may greatly contribute
      to dementia. Current treatment of dementia in PD is based on compensation of the
      profound cholinergic deficiency. Recent studies with the cholinesterase
      inhibitors galantamine, donepezil and rivastigmine show promising results in
      improving cognition and ameliorating psychotic symptoms, which must further be
      confirmed in randomized controlled trials.

PMID- 15480841
TI  - Nicotinic receptors and cognition in Parkinson's Disease: the importance of
      neuronal synchrony.
AB  - Parkinson's Disease (PD) is associated with cognitive deficits. The earliest
      impairment is evident for executive abilities, visuospatial orientation and
      memory. Dopamine deficiency is unlikely to be singly responsible for all
      cognitive changes in PD. Acetyl-choline has an essential role in cognition, thus
      cholinergic transmission may have an important role in non-dopaminergic cognitive
      changes. If so, some cognitive defects could possibly be treated with choline
      esterase inhibitors. A concern is the potential negative motor effect of
      cholinergic medication in PD. Surprisingly, these are reported only in a few
      patients studied. Establishing the relationship between select cognitive deficits
      and nicotinic neurotransmission may lay the foundation for rational
      pharmacotherapy of cognitive dysfunction in PD. We summarize anatomical,
      physiological and pharmacological aspects of nicotinic receptor function. The
      focus is on those nicotine receptor dependent cognitive dysfunctions which are
      likely to contribute to motor impairment. Lastly, we discuss hypotheses
      concerning cholinergic involvement in neuronal synchrony and sensorimotor
      integration in PD.

PMID- 15480842
TI  - Effects of levodopa on cognitive functioning in moderate-to-severe Parkinson's
      disease (MSPD).
AB  - Although improved cognition has been reported in patients with mild Parkinson's
      disease (PD) following the administration of levodopa, mixed results have been
      found in moderately-to-severely affected PD patients (MSPD), particularly in
      studies conducted since 1980. In the present study, 16 MSPD patients were tested
      on separate days, once following overnight levodopa withdrawal and once while
      optimally treated. A battery of neuropsychological tests that assess a range of
      cognitive functions (i.e., attention, language, visuospatial, memory, and
      executive), as well as a measure of depression, were used. Although patients
      performed better on a measure of confrontation naming in the untreated than in
      the treated condition, there were no significant differences for any of the other
      cognitive variables or for the depression scale variable. Thus, these data
      suggest that there are generally no adverse or beneficial effects of levodopa
      therapy on cognition in MSPD patients.

PMID- 15480843
TI  - Antiapoptotic effects of budipine.
AB  - Apoptosis is one essential step for neuronal death in the nigrostriatal region in
      patients with Parkinson's disease. Cytotoxic tumor necrosis factor-alpha (TNF
      alpha) and the proinflammatory cytokine interleukin-6 (Il-6) provide a
      proapoptotic environment. We investigated the influence of the antiparkinsonian
      compound budipine on the release of TNF-alpha and Il-6 in peripheral blood
      mononuclear cells (PBMC) and on the degree of cisplatin induced apoptotic cell
      death in SH-SY 5Y human neuroblastoma cells. 10(-7), 10(-8), 10(-9) mol/l of
      budipine significantly reduced release of TNF-alpha and Il-6 in PBMC and
      decreased apoptotic cell death after 50 hours and 74 hours in the SH-SY 5Y cells.
      Our results suggest, that budipine administration provides an antiapoptotic
      environment and slows neuronal apoptotic and inflammatory mediated loss of
      neurons.

PMID- 15480844
TI  - Dopamine receptor agonists in the therapy of Parkinson's disease.
AB  - Forty years after its introduction by Birkmayer and Hornykiewicz (1961), L-DOPA
      based therapy of Parkinson's disease remains the central pillar in the management
      of the disorder. Nevertheless, it is not unproblematic, and dopamine receptor
      agonists play increasingly important roles in antiparkinsonian therapy.
      Pharmacological and pharmacokinetic properties of these agents are briefly
      reviewed and followed by a detailed summary of available literature concerning
      controlled trials in Parkinson's disease. It is concluded that there is little
      unequivocal evidence to suggest that any of the major dopamine receptor agonists
      should be invariably preferred in the therapy of Parkinson's disease; their
      application must be based on the needs and responses of individual patients.

PMID- 15480845
TI  - Antiparkinsonian medication is not a risk factor for the development of
      hallucinations in Parkinson's disease.
AB  - BACKGROUND: It was commonly assumed that psychotic phenomena in Parkinson's
      disease (PD) are mainly drug related. Accumulating evidence suggests the
      existence of other risk factors for psychosis in PD. Aims. To evaluate the
      contribution of the drug profile of patients with PD to emergence of
      hallucinations. METHODS: We compared patients with and without hallucinations,
      using Cox proportional hazards model, concerning drug profile at the time of
      hallucinations emergence. RESULTS: Of 422 consecutive patients, 113 had dementia,
      while 90 patients experienced hallucinations (46 had both dementia and
      hallucinations). The mean levodopa dose for the group of patients with
      hallucinations was 650 +/- 279 mg/day at the time of hallucinations onset, which
      was not significantly different from the levodopa dose at last visit for the
      group without hallucinations (621 +/- 326 mg/day). Supplementary treatment with
      amantadine, selegiline, dopamine agonists, entacapone and anticholinergics did
      not increase the risk for the development of hallucinations. CONCLUSIONS: We did
      not confirm drug treatment as a risk factor for hallucinations in PD. Our study
      suggests the existence of "endogenic" factors as substantial contributors in the
      genesis of PD hallucinations. The clinical implications may be earlier
      administration of antipsychotic treatment and not as traditionally accepted, dose
      reduction of antiparkinsonian drugs.

PMID- 15480846
TI  - Novel bifunctional drugs targeting monoamine oxidase inhibition and iron
      chelation as an approach to neuroprotection in Parkinson's disease and other
      neurodegenerative diseases.
AB  - Iron has been shown to accumulates at site where neurons degenerate in
      neurodegenerative diseases of Parkinson's disease, Alzheimer's disease,
      Huntington disease, amyotrophic lateral sclerosis and Friedreich ataxia. Iron is
      thought to participate or initiate oxidative stress via generation of reactive
      oxygen species (ROS), such as hydroxyl radical. Iron chelators are
      neuroprotective and prevent 6-hydroxydoapmine and MPTP dopaminergic neurotoxicity
      in rats and mice. However, their action on monoamine oxidase (MAO) A and B have
      not been determined previously since MAO-B inhibitors have been shown to be
      neuroprotective in cellular and animal models of Parkinson's disease. The
      chelators 8-hydroxyquinoline, O-phenanthroline, 2,2'-dipyridyl, U74500A and
      U74600F showed a preference for inhibition of rat brain mitochondrial MAO-A over
      MAO-B. Their IC(50) ranged from 10(-3) M to 10(-6) M, with 21-amino steroids
      (U74500A and U74006F) showing a greater selectivity and potency for MAO-A.
      Desferrioxamine (desferal), a prototype potent iron chelator, exhibited
      relatively poor MAO inhibitory. The inhibitions of MAO-A and B by 21-amino
      steroids (Lazaroids) were time dependent and irreversible. Those initiated by 8
      hydroxyquinoline, 2,2'-dipyridyl and O-phenanthroline were fully reversible by
      enzyme dilution experiments. Both Fe(2+) and Fe(3+) reverse the MAO-A and B
      inhibition induced by the latter chelators, but not those initiated by 21-amino
      steroids. The data infer that either the inhibition of MAO by 21-amino steroids
      is either the resultant of their conversion to an irreversible covalently bound
      ligand or that the iron chelation moiety and MAO inhibitory activity in these
      compounds are not mutually shared. The results suggest that bifunctional brain
      penetrable drugs with iron chelating property and MAO inhibitory activity in
      could be the most feasible approach for neuroprotection in neurodegenerative
      diseases. Such drug would prevent participation of elevated iron in oxidative
      stress and formation of reactive hydroxyl radical, via its interaction with
      H(2)O2 (Fenton chemistry), generated as a consequence MAO and other oxidative
      enzyme reactions to generative cytotoxic reactive hydroxyl radical. We have now
      developed several of these compounds with neuroprotective, MAO inhibitory and
      iron chelating properties from our prototype iron chelators, VK-28 possessing
      propargylamine moiety of our anti-parkinson drug, rasagiline.

PMID- 15480847
TI  - Huntington's disease: pathomechanism and therapeutic perspectives.
AB  - Huntington's disease is an autosomal dominantly inherited progressive
      neurodegenerative disorder. The mutant gene has been localised to chromosome
      4p16.3. The gene product huntingtin is widely distributed in both neurones and
      extraneuronal tissues. The mutation in Huntington's disease involves the
      expansion of a trinucleotide (CAG) repeat encoding glutamine. The etiology of
      Huntington's disease is yet unknown but increasing evidence suggests important
      role of altered gene transcription, mitochondrial dysfunction and excitotoxicity.
      The expanded polyglutamine stretch leads to a conformational change and abnormal
      protein-protein interactions. Mutant huntingtin can bind to transcription
      factors, resulting in reduced levels of acetylated histones. One consequence of
      this appears to be a decreased expression of genes which may play critical roles
      in neuronal survival. To date, a number of palliative therapies have been
      demonstrated to be effective in reducing the motor features, and particularly the
      chorea, but no treatment is at hand for the other symptoms of Huntington's
      disease. However, these treatments produce very limited symptomatic benefit. In
      the absence of disease-modifying treatment, the other avenue is the neural
      transplantation.However, recent advances in understanding have furnished new hope
      that a therapeutic strategy may one day be possible.

PMID- 15480848
TI  - Functional imaging in Tourette's syndrome.
AB  - The cause or causes of Tourette's syndrome (TS) remain unknown. Functional
      imaging studies have evaluated several implicated neurotransmitter systems and
      focused predominantly on the frequency or severity of tics. The results have been
      inconclusive and frequently contradictory with little light shed on pathogenetic
      mechanisms. However, metabolic derangements have been demonstrated within regions
      of the basal ganglia, limbic system and sensori-motor cortex and are in keeping
      with the concept of TS as both a motor and behavioral disorder. TS has long been
      regarded an involuntary movement disorder. However, many patients have stated
      that without the premonitory sensation, there would be no tics. For this reason,
      it has been suggested that the premonitory urge may be considered the involuntary
      component of TS and the performance of the tic merely a voluntary response.
      Future studies are needed to differentiate functional changes relating to urge
      from those associated with the performance of tics and tic suppression.

PMID- 15480849
TI  - Transgenic activation of Ras in neurons increases synapse formation in mouse
      neocortex.
AB  - The small G protein Ras, which is a molecular switch in neurotrophic signal
      transduction, is implicated in synaptic plasticity and synapse development during
      ontogeny and in the adult nervous system. To characterise the involvement of Ras
      dependent signaling in synaptogenesis, the cortical synapse-to-neuron ratio was
      investigated in synRas mice overexpressing Val12-Ha-Ras in postmitotic neurons
      (introduced by Heumann, 2000). The number of synapses per neuron was analysed in
      cortical layers II/III of the somatosensory cortex at different stages of
      postnatal development by stereological methods. The synapse-to-neuron ratio was
      still identical in wild-type and synRas mice at postnatal day 4 before the onset
      of transgene expression. At P12, P47 and in the adult, analyses revealed a
      significant increase in the synapse-to-neuron ratio in synRas mice which
      correlated with the strength of transgene expression. The data presented here
      provide evidence that Ras activity might be profoundly involved in synaptogenesis
      by reinforcing the formation or maintenance of synapses during the development
      and in the adult.

PMID- 15480850
TI  - Correlations between IL-4, IL-12 levels and CCL2, CCL5 levels in serum and
      cerebrospinal fluid of multiple sclerosis patients.
AB  - Multiple sclerosis (MS) is an inflammatory disease of the central nervous system
      (CNS). Both cytokines and chemokines have been implicated in the pathogenesis of
      MS. The aim of the study was to assess whether cytokine levels are correlated
      with chemokine levels during a different stage of relapsing-remitting MS (RR-MS).
      The study included 53 patients with RR-MS (20 subjects in stable stage and 18
      patients with relapse). By ELISA method, the levels of the interleukin-4 (IL-4),
      interleukin-12 (IL-12), CCL2 and CCL-5 chemokines were measured both in serum and
      cerebrospinal fluid (CSF) of all patients. The serum IL-4 and IL-12 levels and
      CSF CCL5 level of patients with stable RR-MS were significantly different from
      the control level and the IL-12 levels were correlated with CCL5 levels in serum.
      During the relapse, a significant change in chemokine levels both in serum and
      CSF and IL-12 in CSF were noted, however no correlations were found between
      cytokines and chemokines.

PMID- 15480851
TI  - The -22c/t polymorphism in presenilin 1 gene is not connected with late-onset and
      early-onset familial Alzheimer's disease in Poland.
AB  - The -22c/t polymorphism in the promoter of the presenilin 1 gene is associated
      with increased risk for Alzheimer's disease (AD) in some populations. It was
      shown that -22c allele is connected with two-fold decrease in promoter activity.
      We studied the impact of the polymorphism in groups of Polish late-onset and
      early-onset AD patients. Our results suggest that -22c/t polymorphism is not
      connected with AD in Polish population. The -22t allele showed a high degree of
      linkage disequilibrium with -2797 insertion of 13 bp. An additional -2923g/t
      polymorphism is also not connected with -22c/t and is not a risk factor for AD.

PMID- 15480852
TI  - L-carnitine and creatine in Friedreich's ataxia. A randomized, placebo-controlled
      crossover trial.
AB  - Impaired oxidative phosphorylation is a crucial factor in the pathogenesis of
      Friedreich's ataxia (FA). L-carnitine and creatine are natural compounds that can
      enhance cellular energy transduction. We performed a placebo-controlled triple
      phase crossover trial of L-carnitine (3 g/d) and creatine (6.75 g/d) in 16
      patients with genetically confirmed FA. Primary outcome measures were
      mitochondrial ATP production measured as phosphocreatine recovery by 31Phosphorus
      magnetic resonance spectroscopy, neurological deficits assessed by the
      international co-operative ataxia rating scale and cardiac hypertrophy in
      echocardiography. After 4 months on L-carnitine phosphocreatine recovery was
      improved compared to baseline (p<0.03, t-test) but comparison to placebo and
      creatine effects did not reach significance (p=0.06, F-test). Ataxia rating scale
      and echocardiographic parameters remained unchanged. Creatine had no effect in FA
      patients. L-carnitine is a promising substance for the treatment of FA patients,
      and larger trials are warranted.

PMID- 15480853
TI  - Depth of word processing in Alzheimer patients and normal controls: a
      magnetoencephalographic (MEG) study.
AB  - Effects related to depth of verbal information processing were investigated in
      probable Alzheimer's disease patients (AD) and age matched controls. During word
      encoding sessions 10 patients and 10 controls had either to decide whether the
      letter "s" appeared in visually presented words (alphabetical decision, shallow
      encoding), or whether the meaning of each presented word was animate or inanimate
      (lexical decision, deep encoding). These encoding sessions were followed by test
      sessions during which all previously encoded words were presented again together
      with the same number of new words. The task was then to discriminate between
      repeated and new words. Magnetic field changes related to brain activity were
      recorded with a whole cortex MEG.5 probable AD patients showed recognition
      performances above chance level related to both depths of information processing.
      Those patients and 5 age matched controls were then further analysed. Recognition
      performance was poorer in probable AD patients compared to controls for both
      levels of processing. However, in both groups deep encoding led to a higher
      recognition performance than shallow encoding. We therefore conclude that the
      performance reduction in the patient group was independent of depth of
      processing. Reaction times related to false alarms differed between patients and
      controls after deep encoding which perhaps could already be used for supporting
      an early diagnosis. The analysis of the physiological data revealed significant
      differences between correctly recognised repetitions and correctly classified new
      words (old/new-effect) in the control group which were missing in the patient
      group after deep encoding. The lack of such an effect in the patient group is
      interpreted as being due to the respective neuropathology related to probable AD.
      The present results demonstrate that magnetic field recordings represent a useful
      tool to physiologically distinguish between probable AD and age matched controls.

PMID- 15480854
TI  - Role of catecholamines in glucagon-induced thermogenesis.
AB  - The present work was undertaken in order to investigate whether the observed
      thermogenesis following glucagon injection requires the participation of
      catecholamines. Our experiments aim at studying the effects of intraperitoneal
      injection of glucagon on metabolic rates, plasma catecholamine and fuel
      metabolites in guanethidine-treated ducklings reared at thermoneutrality (25
      degrees C). The chronic guanethidine treatment induced a marked decrease in
      catecholamines levels in peripheral tissues (heart, muscle and intestine) but not
      in adrenals. At thermoneutrality, intraperitoneal injection of glucagon had lower
      thermogenic effects in guanethidine-treated compared to control ducklings.
      Glucagon injection elicited a concomitant increase of plasma norepinephrine,
      metabolic rate and energy metabolites in control ducklings, whereas in
      guanethidine-treated ducklings, the plasma catecholamines and metabolic rate did
      not undergo any consistent change. The thermogenic action of glucagon in birds
      involves at least the mobilization of lipids and catecholaminergic system
      stimulation.

PMID- 15480855
TI  - A temperature-dependent inhibitory activity of serum on the capacity of
      Saccharomyces cerevisiae-derived hepatitis B surface antigen to bind to
      monocytes.
AB  - Hepatitis B surface antigen, when produced in yeast (rHBsAg), is capable of
      binding to cells that express the lipopolysaccharide coreceptor CD14. This
      interaction is enhanced by a serum protein, the lipopolysaccharide binding
      protein (LBP). Here we report that most of the rHBsAg particles that attached to
      monocytes at 0 degrees C, were not endocytosed but were released back into the
      serum-containing binding buffer at 37 degrees C. Additionally, serum-dependent
      binding at 37 degrees C was weak when compared to the serum-dependent attachment
      at 0 degrees C. Pre-incubation at 37 degrees C of cells together with serum did
      not abolish binding of freshly added rHBsAg at 0 degrees C. However, pre
      incubation of rHBsAg with serum at 37 degrees C reduced attachment to cells
      following incubation at 0 degrees C. Soluble CD14 and LBP, two serum proteins
      which can act as phospholipid transfer molecules, were shown not to be
      responsible for the inhibitory effect. Pre-incubation at 37 degrees C of rHBsAg
      in serum-free hepatoma cell line-conditioned media resulted in a pronounced
      reduction in subsequent binding to cells at 0 degrees C. These observations
      suggest that the temperature-dependent inhibitory effect is caused by serum
      factors that are probably secreted by hepatocytes.

PMID- 15480856
TI  - Genetic variability of hepatitis C virus in HBV/HCV co-infection and HCV single
      infection.
AB  - To describe the virological profile of HCV in HBV/HCV co-infection, we
      investigated the variability of HVR-1 and NS5A domains, which may be involved in
      viral persistence and replication efficiency. We studied 95 patients: 37 with
      serological markers of HBV/HCV co-infection, 33 with single HBV and 25 with
      single HCV infection. HVR-1 complexity and NS5A gene variability were
      respectively explored by means of PCR-SSCP and direct sequencing. Serum HBV
      genomes were detected in all coinfected patients: 19 also had circulating HCV
      particles (group BC-I), whereas HCV were undetectable in the other 18 (group BC
      II). Group BC-I was characterised by a significantly lower HBV replication
      capacity, that reflects the replicative dominance of HCV, although the dominant
      virus had the same degree of variability as the HCV in single infection. HBV
      viral load was higher in group BC-II, but not significantly different from that
      observed in the single infection. Our data indicate an alternation in replicative
      dominance in co-infection: HBV can suppress HCV replication to undetectable
      levels, whereas HCV may reduce but does not abrogate the replication capacity of
      HBV. Furthermore, in the cases of HCV dominance, circulating HBV genomes did not
      have a significant effect on the viral heterogeneity of HCV.

PMID- 15480857
TI  - Testing the hypothesis of a recombinant origin of the SARS-associated
      coronavirus.
AB  - The origin of severe acute respiratory syndrome-associated corona-virus (SARS
      CoV) is still a matter of speculation, although more than one year has passed
      since the onset of the SARS outbreak. In this study, we implemented a 3-step
      strategy to test the intriguing hypothesis that SARS-CoV might have been derived
      from a recombinant virus. First, we blasted the whole SARS-CoV genome against a
      virus database to search viruses of interest. Second, we employed 7 recombination
      detection techniques well documented in successfully detecting recombination
      events to explore the presence of recombination in SARS-CoV genome. Finally, we
      conducted phylogenetic analyses to further explore whether recombination has
      indeed occurred in the course of coronaviruses history predating the emergence of
      SARS-CoV. Surprisingly, we found that 7 putative recombination regions, located
      in Replicase 1ab and Spike protein, exist between SARS-CoV and other 6
      coronaviruses: porcine epidemic diarrhea virus (PEDV), transmissible
      gastroenteritis virus (TGEV), bovine coronavirus (BCoV), human coronavirus 229E
      (HCoV), murine hepatitis virus (MHV), and avian infectious bronchitis virus
      (IBV). Thus, our analyses substantiate the presence of recombination events in
      history that led to the SARS-CoV genome. Like the other coronaviruses used in the
      analysis, SARS-CoV is also a mosaic structure.

PMID- 15480858
TI  - Genotypes of respiratory syncytial virus group B identified in Uruguay.
AB  - Genotypes of Human respiratory syncytial virus (HRSV) of group B from Uruguay
      were assigned to strains isolated during 1999 and 2001 outbreaks and others
      formerly reported isolated in the period 1989-1996. The nucleotide sequences of
      the C-terminal portion of the G protein were compared to sequences representative
      of previously defined HRSV genotypes. Most Uruguayan strains clustered into five
      of the previously identified genotypes. Nine isolates clustered in two genotypes
      named URU1 and URU2 which were not described up to present. Two of the analyzed
      sequences isolated in 2001 have a six nucleotide duplication that is discussed in
      terms of HRSV variability.

PMID- 15480859
TI  - Genetic diversity of sapovirus in fecal specimens from infants and children with
      acute gastroenteritis in Pakistan.
AB  - A total of 517 fecal specimens collected from infants and children with acute
      gastroenteritis in Karachi city, Pakistan during 1990-1994 were examined for the
      presence of sapovirus by RT-PCR and sequence analysis methods. Sapovirus was
      identified in 17 of 517 (3.2%) specimens. Sapovirus was further clustered into
      three distinct genogroups (I, II and IV) and these presented 70.6%, 23.5% and
      5.9%, respectively. Our results clearly indicated that sapovirus could be
      classified into 7 GI and 4 GII genotypes. It was noteworthy to point out that
      sapovirus detected among Pakistani infants and children with acute
      gastroenteritis demonstrated the great genetic diversity and presented novel
      sapovirus genotypes.

PMID- 15480860
TI  - Pediatricians' views of postpartum depression: a self-administered survey.
AB  - OBJECTIVE: To assess pediatricians' knowledge and views about postpartum
      depression (PPD). METHOD: Self-administered survey of a nationwide random sample
      of general pediatricians. RESULTS: Of 1200 eligible pediatricians sampled, 389
      responded (32%). Half of pediatricians (49%) reported little or no education
      about PPD. Many respondents (51%) underestimated the overall incidence of PPD.
      Most pediatricians (80%) estimated the incidence in their practice as less than
      the published incidence. Few pediatricians felt confident they would recognize
      PPD (31%). Pediatricians were rarely familiar with available screening tools
      (7%). Many pediatricians (51%) felt screening was feasible in their practices. In
      logistic regression analysis, intent to begin screening was independently
      associated with <6 years in practice, positive view of feasibility and greater
      awareness of PPD. CONCLUSIONS: Pediatricians sampled have limited awareness of
      PPD and are unfamiliar with screening tools. Efforts to involve pediatricians in
      screening should address these knowledge barriers.

PMID- 15480861
TI  - Trafficked female sex workers awaiting deportation: comparison with brothel
      workers.
AB  - In 2002, we researched the psychosocial characteristics of 55 women working in
      the commercial brothel-based sex industry in three Israeli cities. This previous
      social epidemiological study focused exclusively on women working in brothels and
      the brothel owners consented to their interviews, suggesting that this might be a
      sample of the most organized brothels with the best social conditions. We
      therefore decided to study a second sample obtained by different referral
      methods. The sample consisted of 49 women in a detention center who are awaiting
      judicial hearings for deportation. This prison sample of sex workers is
      strikingly similar to the previously studied sample of sex workers working in
      brothels in terms of demographic features and working conditions. A higher
      percentage of the prison sample reported depression and somatic symptoms.
      However, this finding is consistent with a reaction to being arrested and
      awaiting deportation. Guided by a life course perspective, in the combined
      sample, we examined whether early exposure to trauma, motherhood and early entry
      into sex work affected current health and mental health. Those who were mothers
      were likely to have entered sex work at a later age but no other aspect of their
      working conditions differed from the non-mothers suggesting that motherhood per
      se did not appreciably change the experience of these mostly trafficked women sex
      workers. Early exposure to trauma increased the likelihood for work-related
      trauma, poor health and mental health outcomes.

PMID- 15480864
TI  - Isolation and characterization of a cellulolytic Geobacillus thermoleovorans T4
      strain from sugar refinery wastewater.
AB  - A novel, cellulolytic, bacterial thermophilic strain, T4, was isolated from sugar
      refinery wastewater in southern Taiwan. This isolate, a Gram-negative, motile,
      aerobically growing sporulating rod, can secrete thermostable endocellulase (endo
      1,4-beta-D-glucanase, EC 3.2.1.4) and hydrolyze carboxymethylcellulose (CMC),
      phosphoric acid-swollen cellulose, Avicel, filter paper, and salicin. When strain
      T4 was grown in CMC medium, the cellulolytic enzyme activity in culture
      supernatants was stable up to 70 degrees C. More than 10% of the original
      activity was still detectable after heating to 100 degrees C with a pH 7.0 for 1
      h. Based on 16S rDNA sequence analysis, DNA base composition, phenotypic and
      physiological characteristics, as well as DNA-DNA hybridization, strain T4 was
      classified as Geobacillus thermoleovorans T4 (DSM 14791 = CCRC 17200). We also
      demonstrated that the type species G. stearothermophilus (DSM 22 = ATCC 12980)
      could hydrolyze amorphous and crystalline (filter paper) celluloses at a rate of
      13 and 14%, respectively, in comparison with strain T4.

PMID- 15480865
TI  - Identification and autonomous replication capability of a chromosomal replication
      origin from the archaeon Sulfolobus solfataricus.
AB  - Here, we describe the identification of a chromosomal DNA replication origin
      (oriC) from the hyperthermophilic archaeon Sulfolobus solfataricus (subdomain of
      Crenarchaeota). By means of a cumulative GC-skew analysis of the Sulfolobus
      genome sequence, a candidate oriC was mapped within a 1.12-kb region located
      between the two divergently transcribed MCM- and cdc6-like genes. We demonstrated
      that plasmids containing the Sulfolobus oriC sequence and a hygromycin-resistance
      selectable marker were maintained in an episomal state in transformed S.
      solfataricus cells under selective pressure. The proposed location of the origin
      was confirmed by 2-D gel electrophoresis experiments. This is the first report on
      the functional cloning of a chromosomal oriC from an archaeon and represents an
      important step toward the reconstitution of an archaeal in vitro DNA replication
      system.

PMID- 15480866
TI  - A phylogenetic analysis of Wadi el Natrun soda lake cellulase enrichment cultures
      and identification of cellulase genes from these cultures.
AB  - Samples of sediments and surrounding soda soils (SS) from the extremely saline
      and alkaline lakes of the Wadi el Natrun in the Libyan Desert, Egypt, were
      obtained in October 2000. Anaerobic enrichment cultures were grown from these
      samples, DNA isolated, and the bacterial diversity assessed by 16S rRNA gene
      clone analysis. Clones derived from lake sediments (LS) most closely matched
      Clostridium spp., Natronoincola histidinovorans, Halocella cellulolytica,
      Bacillus spp., and the Cytophaga-Flexibacter-Bacteroides group. Similar clones
      were identified in the SS, but Bacillus spp. predominated. Many of the clones
      were most closely related to organisms already identified in alkaline or saline
      environments. Two genomic DNA libraries were made from the pooled LS enrichments
      and a single SS-enrichment sample. A novel cellulase activity was identified and
      characterized in each. The lake cellulase ORF encoded a protein of 1,118 amino
      acids; BLASTP analysis showed it was most closely related to an endoglucanase
      from Xanthomonas campestris. The soil-cellulase ORF encoded a protein of 634
      amino acids that was most closely related to an endoglucanase from Fibrobacter
      succinogenes.

PMID- 15480868
TI  - [Novel calcium phosphate formula for filling bone defects. Initial in vivo long
      term results].
AB  - BACKGROUND: Up to now hydroxyapatite (HA) and beta-tricalciumphosphate (beta-TCP)
      ceramics have been routinely sintered at temperatures between 1100 degrees and
      1500 degrees C. Our new calcium ceramic is fabricated by a sol-gel process at 200
      degrees C. The aim of this investigation was to test the biodegradation of and
      the induction of bone formation by this material. MATERIAL AND METHODS: Eighteen
      1-year-old Goettingen minipigs were divided into three groups. Critical size
      defects (>5 cm(3)) in the mandible were treated differently in all three animals
      (group 1: filling with 40% beta-TCP plus 60% HA, group 2: pure HA was applied,
      group 3 served as controls: only gelatinous material was given). Macroscopic and
      microscopic investigations of the former defects were made 8 months
      postoperatively. RESULTS. In groups 1 and 2 biodegradation of more than 93% of
      the new calcium phosphate formula was found 8 months postoperatively and
      considered to be very good. No difference was observed between pure HA (group 2)
      and the combination of HA and beta-TCP (group 1). In both groups complete bone
      formation was seen macroscopically in the former defects. In the control group
      only incomplete bone formation with 48.4% of the defect area was noted. This
      difference was significant ( p<0.001). DISCUSSION: The new calcium phosphate
      formula made by a sol-gel method at 120 degrees C seems to be suitable for
      filling bone defects and is of interest for orthopedic surgery, traumatology,
      craniomaxillofacial surgery, and dentistry.

PMID- 15480869
TI  - [Peri-implant bone formation around cylindrical and conical implant systems].
AB  - BACKGROUND: The treatment of patients with early or immediately loaded dental
      implants has renewed interest in the behavior of osseointegration at the implant
      surface. Whereas it is generally accepted that peri-implant tissue formation and
      mineralization are dependent on the local mechanical environment in the interface
      zone, controversies exist concerning the impact of implant design on peri-implant
      bone formation. The aim of the present study was the in vivo evaluation of peri
      implant bone formation by two different implant systems: cylindrical (ITI) versus
      conical (ILI). MATERIAL AND METHOD: A total of 60 implants (30 ITI and 30 ILI)
      were placed in the cranial and caudal part of the tibia of eight Gottinger
      minipigs. Half of the minipigs were sacrificed at 7 days and 28 days of
      osseointegration. Implant-containing bone specimens were prepared for
      histological and ultrastructural investigations. RESULTS: Histological and
      scanning electron-microscopic investigations showed a direct contact of bone-like
      minerals over the whole implant surface from day 7 of implant/bone interaction.
      Whereas the ILI implant showed direct contact up to the top of the crestal bone,
      ITI implants demonstrated a crestally located narrow gap without ossification
      over the whole experimental period. CONCLUSION: Our investigations support the
      hypothesis of an implant design-inherent emergence and maintenance of crestal
      bone.

PMID- 15480870
TI  - [Genioplasty alone and in combination. Long-term results with emphasis on
      sensitivity and photoanalysis].
AB  - PURPOSE: Striving for beauty and expressiveness is a deeply rooted human
      attitude. The lower jaw-especially the mentum-plays an important role in the
      perception of the face as an instrument of communication. According to Grammer a
      distinctive lower jaw is an essential characteristic feature of male
      attractiveness. MATERIAL AND METHODS: During a period of 10 years 58 patients
      underwent genioplasty. A follow-up examination was performed in 49 patients
      (complete sensitivity evaluation: 33 patients, complete photoanalysis: 30
      patients). To reduce radiation due to cephalometric radiography a simple
      photometric method for cephalometry was developed and applied. Particular
      attention was directed at sensitivity of the mental nerve after genioplasty.
      RESULTS: To the best of our knowledge, this is the first time that photos of the
      right profile were compared with those of the left side. Unexpectedly,
      intraindividual differences dependent on the facial side (right and left) could
      be found in the relationship of the lower to the upper face and in the proportion
      of the profile angle and the nasomental angle. After three-dimensional
      genioplasty these differences were reduced and facial asymmetry was improved.
      Comparing the right with the left side the average difference of the nasomental
      angle was reduced from 2.5 degrees to 0.6 degrees on average. The profile angle
      was changed by genioplasty from 19 degrees on average to 15 degrees ("ideally" 10
      degrees , the so-called upright face). According to Schwarz the ideal height of
      the mentum (stomion-menton) should amount to 66% of the total lower face.
      Especially by combined dorsal and cranial positioning of the mentum a reduction
      from 85 to 68% was achieved. Postoperatively 24 of 33 patients (73%) showed
      disturbances of the mental nerve. After at least 1 year following the operation,
      normal sensitivity of the lower lip and chin of both sides was evaluated by
      almost all of these patients (19 of 24 = 79%). Especially all patients having had
      only a single genioplasty recovered totally from a neurosensory deficit.
      CONCLUSIONS: Genioplasty can be considered to be a reliable procedure to achieve
      harmony of the lower face.

PMID- 15480871
TI  - [Chronic cutaneous infiltration with abscess and fistula formation. A type of
      clinical course in atypical mycobacteriosis].
AB  - BACKGROUND: Cutaneous lesions of atypical mycobacteriosis are very rare in
      Western Europe. Both the slow disease progression and the rather unspecific
      clinical appearance of the chronic infiltration render cutaneous mycobacteriosis
      a diagnostic challenge. In this communication, we present an uncommon, biphasic
      course of a cutaneous atypical mycobacteriosis. CASE REPORT: A 3-year-old child
      was referred to our institution due to submandibular cutaneous infiltration
      together with subcutaneous abscess formation. There was no carious lesion or
      other odontogenic potential source of infection. First-line therapy was incision
      of the abscess and local curettage to obtain a specimen for histologic and
      microbiologic evaluation, which revealed atypical mycobacteria. In spite of local
      curettage, only partial remission of the cutaneous infiltration was achieved.
      When the child was readmitted 9 months later, the lesion had progressed to a
      scrofulosis-like appearance even though specific antibiotic treatment had been
      administered. Complete surgical excision of the affected skin and extirpation of
      the respective lymph node and fistula was performed as second-line therapy.
      Complete remission was achieved without further adjuvant treatment. DISCUSSION:
      Our case demonstrates the problems that may arise with this rare type of
      mycobacterial infection. In all probability, scratch artifacts due to atopic
      dermatitis provided the source/entry of the infection in this specific case. Both
      histopathologic findings and clinical appearance were suggestive of classic
      cutaneous tuberculosis (tuberculosis cutis colliquativa), although it was in fact
      an atypical mycobacteriosis. Furthermore, obstinate persistence after minor
      surgical intervention and even after specific (triple) antibiotic treatment
      illustrates the difficulties of limited, minimally invasive treatment.

PMID- 15480875
TI  - De novo deletions in the paired domain of PAX6 in south Indian aniridic patients.
AB  - We analyzed the sequence variation in the coding exons of PAX6 in eight unrelated
      south Indian pedigrees with one aniridic individual in each family. Mutations
      were detected by PCR, SSCP and allele-specific cloning followed by sequencing.
      Here we report two de novo deletion mutations, c.537delA (codon 59) and
      c.728del14 (codon 122), in the paired domain of PAX6. These deletions probably
      represent null or hypomorphic alleles consistent with PAX6 haploinsufficiency as
      the underlying genetic factor of aniridia.

PMID- 15480872
TI  - [Central giant cell granuloma and osteitis fibrosa cystica of
      hyperparathyroidism. A challenge in differential diagnosis of patients with
      osteolytic jawbone lesions and a history of cancer].
AB  - BACKGROUND: Giant cell lesions of the bone present similar histological features.
      The differential diagnosis comprises central giant cell granuloma, giant cell
      tumor of bone, and osteitis fibrosa cystica (brown tumor) in combination with
      hyperparathyroidism. Since these lesions may mimic metastatic bone disease in
      patients with a history of cancer, a malignant process has to be considered.
      Since the treatment and prognosis of these entities-benign versus malignant
      osteolytic bone processes-differ greatly, definitive differential diagnosis is of
      utmost importance. CASE REPORT: Two patients presenting with osteolytic lesions
      of the maxilla are reported here. In both cases a history of cancer (breast and
      prostate) suggested bone spreading of these malignant tumors. The clinical and
      histological findings were similar in both patients. One lesion was diagnosed as
      central giant cell granuloma, the other was found to be brown tumour in osteitis
      fibrosa cystica as an initial manifestation of hyperparathyroidism. DISCUSSION:
      The presented cases demonstrate the difficulties in establishing the correct
      diagnosis of patients found to have osteolytic lesions of the jawbones which is
      critical for the appropriate management of these patients. The article discusses
      the different entities of osteolytic lesions of the jawbones and the necessary
      diagnostic and therapeutic approach.

PMID- 15480874
TI  - Detection of allelic imbalance in the gene expression of hMSH2 or RB1 in
      lymphocytes from pedigrees of hereditary, nonpolyposis, colorectal cancer and
      retinoblastoma by an RNA difference plot.
AB  - A number of phenotypes in hereditary disorders or common diseases are associated
      with specific genotypes. However, little is known about the molecular basis of
      phenotypic variation among individuals carrying the same mutation or
      polymorphism. Here, a highly quantitative approach was taken to examine a
      relative amount of mRNA from two polymorphic alleles with a coefficient of
      variation of less than 10% using an RNA difference plot (RDP). RDP analysis
      revealed that most genes examined were expressed in equal amount from the two
      alleles in normal lymphocytes. In contrast, the relative amounts of hMSH2 or RB1
      mRNAs carrying premature termination codons were significantly reduced compared
      with those of wild-type mRNAs in lymphocytes from carriers of hereditary,
      nonpolyposis, colorectal cancer and hereditary retinoblastoma. The balance of
      allelic expression of the RB1 was also significantly impaired in a pedigree of
      retinoblastoma carrying a missense mutation in codon 661. The relative expression
      of the mutant to the wild-type RB1 alleles among the carriers varied from 0.40 to
      2.39. The analysis of the expression diversity of a disease-associated allele by
      RDP could provide a novel approach to elucidating the mechanisms underlying
      phenotypic variation among individuals carrying an identical mutation or
      polymorphism at a single locus.

PMID- 15480876
TI  - Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and
      molecular genetic analysis of 86 families.
AB  - The frequency of autosomal-dominant cerebellar ataxia (ADCA) subtypes was
      examined in 86 unrelated families originating from Nagano prefecture. In Nagano,
      the prevalence of spinocerebellar degeneration (SCD) was approximately 22 per
      100,000 population. Among ADCA families, SCA6 was the most prevalent subtype (16
      families, 19%), followed by DRPLA (nine families, 10%), SCA3/MJD (three families,
      3%), SCA1 (two families, 2%), and SCA2 (one family, 1%). No families with SCA7,
      SCA12, or SCA17 were detected. Compared with other districts in Japan, the
      prevalence of SCA3/MJD was very low in Nagano. More interestingly, the ratio of
      genetically undetermined ADCA families was much higher in Nagano (55 families,
      65%) than in other districts in Japan. These families tended to accumulate in
      geographically restricted areas such as Kiso, Saku, and Ina, indicating that the
      founder effect might be responsible for the high frequency of ADCA in these
      areas. Most patients clinically showed slowly progressive pure cerebellar ataxia
      of late-onset (ADCA III). In the case of 36 patients from 36 genetically
      undetermined ADCA III families, however, no one was completely consistent with
      the founder allele proposed for 16q-ADCA. These results indicate that there might
      be genetically distinct ADCA subtypes in Nagano.

PMID- 15480877
TI  - Comparative study of the haplotype structure and linkage disequilibrium of
      chromosome 1p36.2 region in the Korean and Japanese populations.
AB  - The patterns of linkage disequilibrium (LD) in the human genome provide important
      information for disease gene mapping. LDs may vary depending on chromosomal
      regions and populations. We have compared LD and haplotypes defined by SNPs in
      the chromosome 1p36.2 region of the Korean and Japanese populations. Fifty-eight
      SNPs in about 418 kb ranging from tumor necrosis factor receptor 2
      (TNFR2:TNFRSF1B) to procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) gene
      were examined in 96 healthy Koreans and Japanese each by direct sequencing and
      fluorescence correlation spectroscopy combined with the PCR-sequence specific
      primer method (PCR-SSP-FCS), respectively. Upon pair-wise LD analysis, a total of
      25 and 16 out of 58 SNPs greater than MAF 10% were included in LD blocks,
      encompassing almost 81 kb and 55 kb in total, in Koreans and Japanese,
      respectively. Both similarities and differences were observed in LD strength and
      haplotype frequencies between the populations. Considerable similarities were
      observed in the telomeric region where a long-range block of approximately 80 kb
      including three genes was found to have strong LDs in both Koreans and Japanese.
      Significant difference in LD strength was present near the TNFR2 region between
      the Japanese and Korean populations.

PMID- 15480878
TI  - A novel three extra-repeat insertion in the prion protein gene (PRNP) in a
      patient with Creutzfeldt-Jakob disease.

PMID- 15480879
TI  - Alternative splicing in the N-terminus of Alzheimer's presenilin 1.
AB  - Presenilin 1 (PS1) is mutated in the majority of familial cases of Alzheimer
      disease (AD). Although it is clear that PS1 is involved in the processing of the
      amyloid precursor protein (APP), the exact function of PS1 is still elusive.
      Human presenilin 1 (PS1) is alternatively spliced, resulting in the presence or
      absence of a four-amino acid motif, VRSQ, in the PS1 N-terminus. In human
      tissues, both isoforms are expressed. Here we report that mouse and rat only
      express the longer PS1 isoform. The presence of this motif introduces a potential
      phosphorylation site for protein kinase C. Because the splice occurs in the
      region of PS1 that we have previously shown to bind to rabGDI, this might provide
      a regulatory mechanism for this interaction. Our data show that the -VRSQ isoform
      binds rabGDI, but the +VRSQ does not. Moreover, mutation of the putatively
      phosphorylated threonine in PS1 disrupts the binding to rabGDI, showing its
      importance for the interaction. To our knowledge this is the first study showing
      a functional difference between PS1 splice variants. The possible consequences
      for APP processing and the pathogenesis of AD are discussed.

PMID- 15480880
TI  - Rapid identification of Legionella pneumophila serogroups by latex agglutination.

PMID- 15480881
TI  - Alveolar echinococcosis in a patient without hepatic disturbance and with unusual
      humoral immune response.

PMID- 15480882
TI  - Prevalence of herpes simplex virus, varicella zoster virus and cytomegalovirus in
      HIV-positive and HIV-negative patients with viral retinitis in India.

PMID- 15480883
TI  - Evaluation of the current National Committee for Clinical Laboratory Standards
      guidelines for screening and confirming extended-spectrum beta-lactamase
      production in isolates of Escherichia coli and Klebsiella species from bacteremic
      patients.
AB  - The National Committee for Clinical Laboratory Standards (NCCLS) recommendations
      for screening and confirming the production of extended-spectrum beta-lactamases
      (ESBLs) were evaluated in 115 isolates of Escherichia coli and 157 isolates of
      Klebsiella spp. from Israeli patients with bacteremia. All isolates were screened
      using cefotaxime, ceftazidime, and cefpodoxime discs. Confirmatory tests using
      pairs of discs containing ceftazidime, cefotaxime, or cefpodoxime in which
      clavulanic acid was added to one of the discs in each pair [inhibitor-potentiated
      disc diffusion test (IPDDT)] and two double-sided E test strips containing
      ceftazidime or cefotaxime with and without clavulanic acid were performed on all
      isolates regardless of the results of screening tests. Isolates that tested
      positive by one or more confirmatory tests were considered ESBL producers.
      Overall, 69 (25.4%) strains were found to be ESBL producers. The sensitivity of
      the NCCLS screening criteria ranged between 98.6% for cefotaxime and 92.8% for
      ceftazidime, and the specificity ranged between 100% for cefotaxime and
      cefpodoxime and 99.0% for ceftazidime. The sensitivity of the confirmatory tests
      ranged between 97.1% for the cefotaxime E test and only 75.4% for the ceftazidime
      IPDDT discs. All 64 isolates that fell in the intermediate and resistant
      categories for cefotaxime, as well as all 41 in the same categories for
      ceftazidime and 68 of 69 in these categories for cefpodoxime, were confirmed as
      ESBL producers. The use of multiple antimicrobial discs for screening isolates
      and combinations of IPPDT discs is needed to improve the sensitivity of
      confirmatory testing. It is recommended that isolates falling in the intermediate
      and resistant categories in disc diffusion testing be reported as ESBL producers.
      The use of confirmatory tests should be limited to organisms with inhibition zone
      diameters ranging between the NCCLS recommendations for ESBL screening and the
      intermediate category breakpoints.

PMID- 15480884
TI  - Prevalence of restriction fragment length polymorphism patterns of hepatitis B
      virus compatible with genotype D in Lebanon.

PMID- 15480885
TI  - Evaluation of a commercial enzyme immunoassay for HIV screening in urine.
AB  - A cross-sectional study was conducted to evaluate the utility of a commercial
      enzyme immunoassay (EIA) as a screening test for detecting HIV-1 antibody in
      urine in a population at risk for HIV infection in Catalonia, Spain. Paired urine
      and serum samples were collected consecutively from 99 patients who attended two
      drug-dependency treatment centres and 151 patients who attended a sexually
      transmitted diseases (STD) clinic in Barcelona. Antibodies against HIV in urine
      samples were detected using the Calypte HIV-1 Urine EIA (Calypte Biomedical
      Corporation, Berkeley, CA, USA) and confirmed by urine-based Western blot (WB)
      analysis. Sera were analysed using Bioelisa HIV-1+2 EIA (Biokit Laboratories,
      Barcelona, Spain), and the results were verified using serum-based WB analysis.
      Results of both urine and serum testing were available for 246 of 250
      participants. For 52 individuals the results of both urine and serum testing were
      positive and for five the results were discordant (2 with urine-negative/serum
      positive results and 3 with urine-positive/serum-negative results). The
      respective sensitivity and specificity values obtained for the urine EIA were
      100% and 96.2% for intravenous drug users (IDUs) and 80% and 99.3% for persons
      attending the STD clinic. According to the 1997 UNAIDS/WHO strategy I
      recommendations, these values are acceptable for surveillance purposes,
      particularly in populations with a high prevalence of HIV infection.

PMID- 15480886
TI  - Usual interstitial pneumonia associated with cytomegalovirus infection after
      percutaneous transluminal coronary angioplasty.
AB  - An unusual case of cytomegalovirus (CMV) pneumonia in a diabetic patient is
      presented. The diagnosis was based on typical histopathological findings
      including intranuclear inclusion bodies combined with molecular identification of
      CMV in tissue specimens. The possibility of CMV reactivation associated with a
      previous cardiac procedure, which led to the development of usual interstitial
      pneumonia, is discussed. Clinicians should be aware of CMV-associated severe
      bilateral pneumonia developing after cardiac procedures even in non-transplant
      patients. The correct diagnosis depends on clinical awareness in the appropriate
      setting along with proof of viral infection.

PMID- 15480887
TI  - Expression profiling of rice segregating for drought tolerance QTLs using a rice
      genome array.
AB  - Plants alter their gene expression patterns in response to drought. Sometimes
      these transcriptional changes are successful adaptations leading to tolerance,
      while in other instances the plant ultimately fails to adapt to the stress and is
      labeled as sensitive to that condition. We measured the expression of
      approximately half of the genes in rice ( approximately 21,000) in phenotypically
      divergent accessions and their transgressive segregants to associate stress
      regulated gene expression changes with quantitative trait loci (QTLs) for osmotic
      adjustment (OA, a trait associated with drought tolerance). Among the parental
      lines, a total of 662 transcripts were differentially expressed. Only 12 genes
      were induced in the low OA parent, CT9993, at moderate dehydration stress levels
      while over 200 genes were induced in the high OA parent, IR62266. The high and
      low OA parents had almost entirely different transcriptional responses to
      dehydration stress suggesting a complete absence of an appropriate response
      rather than a slower response in CT9993. Sixty-nine genes were up-regulated in
      all the high OA lines and nine of those genes were not induced in any of the low
      OA lines. The annotation of four of those genes, sucrose synthase, a pore
      protein, a heat shock and an LEA protein, suggests a role in maintaining high OA
      and membrane stability. Of the 3,954-probe sets that correspond to the QTL
      intervals, very few had a differential expression pattern between the high OA and
      low OA lines that suggest a role leading to the phenotypic variation. However,
      several promising candidates were identified for each of the five QTL including a
      snRNP auxiliary factor, a LEA protein, a protein phosphatase 2C and a Sar1
      homolog.

PMID- 15480888
TI  - cDNA microarray analysis of developing grape (Vitis vinifera cv. Shiraz) berry
      skin.
AB  - Microarray analysis of Vitis vinifera cv. Shiraz developing berries has revealed
      the expression patterns of several categories of genes. Microarray slides were
      constructed from 4,608 PCR-amplified cDNA clones derived from a ripening grape
      berry cDNA library. The mRNA expression levels of the genes represented by these
      cDNAs were measured in flowers, week 2 post-flowering whole berries, week 5, week
      8, week 10 (veraison, green berries), week 12 and week 13 berry skin. In
      addition, a comparison of RNA expression in pigmented and unpigmented berry skin
      at veraison (week 10) was undertaken. Image and statistical analysis revealed
      four sets of genes with distinctive and similar expression profiles over the
      course of berry development. The first set was composed of genes which had
      maximum RNA expression in flowers, followed by a steady decrease in expression.
      The most prominent group within this set were genes which have a role in
      photosynthesis. The second set of cDNAs was dominated by genes involved in
      flavonoid biosynthesis and had a peak of expression week 2 post-flowering. The
      data indicate co-ordinate regulation of flavonoid biosynthetic genes which code
      for the enzymes 4-coumarate-CoA ligase, chalcone synthase, chalcone isomerase,
      flavonone hydroxylase, anthocyanidin reductase and cytochrome b5. The third set
      of cDNAs exhibited maximum expression week 5 post-flowering, midway between
      flowering and veraison, a period of rapid berry growth. This set of cDNAs is
      dominated by genes which code for structural cell wall proteins. The fourth set
      of genes was dramatically up-regulated at veraison and remained up-regulated
      until 13 weeks post-flowering. This set of genes was composed of a diverse range
      of genes, a reflection of the complexity of ripening, most with no known
      function.

PMID- 15480889
TI  - Neurological recovery and its influencing factors in thoracic and lumbar spine
      fractures after surgical decompression and stabilization.
AB  - Surgical decompression and internal fixation of the injured spine have become
      standard procedures in the management of thoracic and lumbar spine fractures, but
      their effectiveness on neurological recovery remains controversial. We report on
      169 consecutive patients with thoracic and lumbar spine fractures who were
      treated by reduction, fusion, and internal fixation using transpedicular screw
      rod systems. Open decompression was carried out in 67 (39.6%) of them, including
      all 42 patients (25%) who presented with initial neurological deficits. At least
      8 months following surgery, 30 (71%) had neurologically improved by one to three
      grades on the Frankel scale. Thirteen (59%) out of 22 patients whose initial
      deficits had been classified as "motor useless" (Frankel grades A to C) could
      walk, at least with support. Thirteen out of 20 patients with posttraumatic
      deficit Frankel D ("motor useful") improved to full recovery (Frankel E). In six
      (3.6%) patients (all from the group of the 127 patients without initial
      neurological deficits), permanent slight postoperative neurological impairment of
      one Frankel grade (E to D) was seen, among them two (1.2%) with new minor motor
      deficit. Neurological outcome was significantly better (p<0.01) in patients
      operated upon within the first 24 h after injury than in those who underwent
      surgery later. Severity of injury also had a negative influence (p<0.001) on
      neurological recovery. Analysis suggests that there may be significant
      neurological improvement in patients treated surgically very early.

PMID- 15480890
TI  - False-negative magnetic resonance angiography with extracranial internal carotid
      artery stenosis: a report of two cases and review of the literature.
AB  - Magnetic resonance angiography (MRA) is increasingly used as a noninvasive means
      to assess internal carotid artery (ICA) stenosis. When used alone, however, MRA
      may not be sufficiently accurate in certain settings to determine whether ICA
      disease meets surgical criteria. Although MRA has been recognized to overestimate
      the degree of stenosis, the authors present two cases in which it severely
      underestimated arterial stenosis. Two male patients, 70 and 40 years old,
      respectively, were admitted with crescendo transient ischemic attacks. Their MRA
      studies suggested nonsurgical lesions of the ICA. After the patients continued to
      demonstrate clinical evidence of embolic disease, digital subtraction angiography
      (DSA) was performed on one patient, and the other received a gadolinium contrast
      enhanced MRA. These tests revealed critical stenosis in each patient. Each was
      taken to the operating room for awake carotid endarterectomy with heparin
      anticoagulation and electroencephalographic monitoring. At surgery, both patients
      were found to have severely stenosed ICAs with complex plaques. MRA to determine
      whether ICA stenosis meets surgical criteria may not be sufficiently accurate in
      certain clinical settings. Additional imaging studies, such as confirmatory
      digital ultrasonography, MRA with gadolinium contrast, or DSA, may be required to
      determine the extent of carotid artery stenosis accurately.

PMID- 15480891
TI  - Biomechanical comparison of inside-outside screws, cables, and regular screws,
      using a sawbone model.
AB  - Our aim was to conduct a biomechanical comparison of the pull-out strengths of
      inside-outside (I/O) screws, cables, and bone screws to determine whether I/O
      screws provide greater pull-out resistance than cables or bone screws, and their
      effectiveness with the screw diameter. There is no remarkable biomechanical
      experimental study comparing the I/O technique with conventional spinal
      techniques. The diameter of the screw heads were also biomechanically tested to
      determine the optimal size that can be used. In this study, 45 blocks of 50x50x5
      mm of "sawbone" (synthetic bone, model 1137, Pacific Research Laboratories,
      Vashon, WA, USA) were used as bone substitutes. Fifteen sets of 14-mm inside
      outside Dynalok screws and nuts, 15 wire cables, and 15 bone screws were inserted
      into a separate sawbone block. An MTS Bionx materials testing machine was used to
      measure the load to failure of each implant. The mean values and standard
      deviations of each group were calculated and Student's t-test was used for
      comparison. The load to failure of the inside-outside screws was significantly
      greater than that of the cables (p<0.0000004) and the regular bone screws
      (p<0.000002). The results also revealed that increasing the diameter of the head
      of the screw also increases the resistance against the pull-out strengths. Thus,
      using a larger screw in occipitocervical stabilization provides safe and stable
      fixation of the occipital bone to the cervical spine. This study also proved that
      sawbone is a useful and reliable alternative to allogenic fresh cadaveric bone
      grafts or animal bones for certain biomechanical testing.

PMID- 15480892
TI  - Growing new kidneys in situ.
AB  - One novel solution to the shortage of human organs available for transplantation
      envisions "growing" new organs in situ via xenotransplantation of developing
      primordia from animal embryos. Renal primordia (metanephroi) transplanted into
      animal hosts undergo organogenesis in situ, become vascularized by blood vessels
      of host origin, and exhibit excretory function. Metanephroi can be stored in
      vitro prior to transplantation and can be transplanted across both concordant
      (rat-to-mouse) and highly disparate (pig-to-rodent) xenogeneic barriers. Here we
      review studies exploring the therapeutic potential for renal organogenesis post
      transplantation of kidney primordia.

PMID- 15480893
TI  - Role of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the
      development of hypertensive organ damage.
AB  - Recently, a novel endothelial oxidized low-density lipoprotein (LDL) receptor,
      lectin-like oxidized LDL receptor (LOX)-1, has been identified by the expression
      cloning of cultured bovine aortic endothelial cells (BAEC). The experimental
      evidence has suggested that LOX-1 may contribute to the development of vascular
      injury. For example, LOX-1 is upregulated in aorta from hypertensive, diabetic,
      and hyperlipidemic model animals. Also, LOX-1 overexpression is observed in
      atherosclerotic regions and damaged kidneys. In hypertensive animals, not only
      antihypertensive drugs but also antioxidant agents suppress the LOX-1
      overexpression. Peroxisome proliferator-activated receptor-gamma (PPARgamma)
      activators inhibit cytokine-stimulated LOX-1 expression, possibly through their
      antioxidant effects, while, in contrast, LOX-1 generates reactive oxygen species
      (ROS). Therefore, ROS may play an important role in both the expression and
      function of LOX-1.

PMID- 15480894
TI  - Dual blockade of the renin-angiotensin system in chronic renal disease: to do or
      not to do.
AB  - The renin-angiotensin-aldosterone system has an important role in the progression
      of both diabetic and nondiabetic nephropathy. Angiotensin-converting enzyme
      inhibitors and angiotensin-II receptor blocker can effectively retard or halt
      this progression. However, their renoprotective effect is not enough, because
      approximately 20% of patients have a progressive course to endstage renal
      disease. There is now clear evidence that combination therapy of two agents is
      more antiproteinuric and, likely renoprotective, than each agent alone. However,
      several critical issues should be addressed before recommending it as standard
      treatment in chronic renal disease.

PMID- 15480895
TI  - Role of mitogen-activated protein kinase in the regulation of transforming growth
      factor-beta-induced fibronectin accumulation in cultured renal interstitial
      fibroblasts.
AB  - BACKGROUND: In diabetic nephropathy, tubulointerstitial fibrosis is an important
      component of renal injury. Transforming growth factor (TGF)-beta is a key
      cytokine that is involved in the pathogenesis of tubulointerstitial fibrosis.
      However, signal transduction cascades of TGF-beta under high-glucose conditions
      remain to be clarified. We undertook this study to elucidate whether mitogen
      activated protein (MAP) kinase and Smad proteins were involved in TGF-beta
      induced fibronectin (FN) production under high glucose in NRK fibroblasts.
      METHODS: After serum restriction, NRK cells were exposed to either normal glucose
      (5.5 mM d-glucose), high glucose (30 mM d-glucose), or 30 mM l-glucose in the
      presence or absence of TGF-beta for 24 h. MAP kinase inhibitors (SB 203580 and PD
      98059) were added to the cultured NRK fibroblasts 2 h before TGF-beta1, and the
      incubations continued for 8 h. The phosphorylation of p38 MAP kinase,
      extracellular signal-regulated kinase (ERK)1/ERK2, and c-Jun N-amino terminal
      kinase (JNK) was assessed by immunoblotting. Reverse transcription-polymerase
      chain reaction (RT-PCR) and Western blotting were performed to determine FN mRNA
      and protein expression, respectively. RESULTS: High glucose significantly
      increased the expression of FN mRNA, by 2.4 +/- 1.4-fold. In the presence of
      either SB 203580 or PD 98059, the high glucose-induced FN mRNA increase was
      completely inhibited. Incubation of NRK fibroblasts for 48 h in 30 mM d-glucose
      did not alter p38 MAP kinase, ERK1/ERK2, or JNK phosphorylation. The addition of
      exogenous TGF-beta1 (1 ng/ml) for 8 h increased FN mRNA by 2.7 +/- 1.1-fold. Both
      the TGF-beta1- and high glucose-induced FN mRNA increases were inhibited by SB
      203580 and PD 98059. Dominant-negative Smad4 did not affect the FN mRNA increase
      induced by TGF-beta1 and high glucose. Exogenous TGF-beta1 under both normal and
      high glucose, enhanced the phosphorylation of both p38 MAP kinase and ERK1/ERK2,
      but not that of JNK. CONCLUSIONS: NRK fibroblasts exposed to high glucose
      demonstrated increased TGF-beta1-induced p38 MAP kinase activation. The FN
      synthesis induced by high glucose and TGF-beta1 was not affected by the Smads
      pathway and was not due to increased osmolarity. The enhanced activation of p38
      MAP kinase may contribute to the altered fibroblast phenotype that leads to
      progressive diabetic nephropathy.

PMID- 15480896
TI  - Mesangial cell Fas ligand: upregulation in human lupus nephritis and NF-kappaB
      mediated expression in cultured human mesangial cells.
AB  - BACKGROUND: Fas ligand (FasL) is a well-known death factor; however, the role of
      FasL in the regulation of human glomerulonephritis remains unclear. METHODS: We
      investigated the renal expression and localization of FasL in various forms of
      human glomerulonephritis by immunohistochemistry, utilizing confocal laser
      scanning microscopy. We further evaluated cytokine-induced FasL expression via
      nuclear factor (NF)kappaB in cultured human mesangial cells (HMC). The level of
      soluble FasL was measured by a specific enzyme-linked immunosorbent assay
      (ELISA). RESULTS: The frequency of glomerular FasL-positive cases was higher in
      lupus nephritis (37.9%) as compared with other forms of glomerulonephritis
      (8.7%). The glomerular FasL score in proliferative lupus nephritis was
      significantly higher than that in nonproliferative forms. Patients with a high
      apoptosis score, severe microhematuria, proteinuria, or decreased renal function
      had a high FasL score. Double immunolabelling demonstrated that the most
      prevalent phenotypes of FasL-positive cells were mesangial cells. In cultured
      HMC, interleukin (IL)1beta, lipopolysaccharide (LPS), or gamma interferon (IFN)
      upregulated membrane-bound FasL. IL1beta significantly, and LPS or gammaIFN
      weakly activated NFkappaB, but none of these agents activated NFkappaB/Rel
      related nuclear factor of activated T cells (NFATc) or IFN regulatory factor-1.
      IL1beta-mediated NFkappaB was completely inhibited in the presence of
      lactacystin, a potent inhibitor of NFkappaB. Lactacystin-mediated inhibition of
      NFkappaB reduced FasL protein levels. Matrix metalloproteinase (MMP)-7, but not
      other MMPs (1, 2, 3, 8, or 9), significantly sensitized HMC to release soluble
      FasL after IL1beta stimulation. CONCLUSIONS: The results suggest that: (1)
      upregulation of mesangial FasL may contribute to the glomerular inflammation in
      proliferative lupus nephritis in vivo; (2) proinflammatory cytokines, in
      particular IL1beta, produced in nephritis can upregulate FasL via the
      transcription factor NFkappaB in HMC; and (3) MMP-7-mediated release of soluble
      FasL could control the mesangial inflammation.

PMID- 15480897
TI  - Expression of MMP-9 in mesangial cells and its changes in anti-GBM
      glomerulonephritis in WKY rats.
AB  - BACKGROUND: Matrix metalloproteinase (MMP)-9, a member of the MMP family with
      specificity towards type IV collagen, is implicated in the turnover of the
      extracellular matrix in the kidney. To elucidate its physiological and
      pathophysiological significance, we examined the expression and localization of
      MMP-9 in the normal kidney and the changes in these features during the course of
      anti-glomerular basement membrane (GBM) glomerulonephritis induced in WKY rats,
      along with the changes in these features of tissue inhibitor of metalloproteinase
      1 (TIMP-1) and MMP-2. METHODS: The expression of MMP-9, TIMP-1 and MMP-2 mRNA was
      quantified by ribonuclease protection assay, and the gelatinolytic activities of
      MMP-9 and MMP-2 were evaluated by gelatin zymography. The localization of MMP-9
      was visualized by immunohistochemistry and immunofluorescence microscopy.
      RESULTS: The ribonuclease protection assay indicated the almost exclusive
      expression of MMP-9 mRNA in the glomerulus of normal kidneys.
      Immunohistochemistry and double-label immunofluorescence microscopy showed that
      MMP-9 was localized in the mesangial cells. During the course of anti-GBM
      glomerulonephritis, the expression of MMP-9 mRNA in glomeruli increased on day 1,
      peaked on days 3 to 7, and then decreased on day 14. The change in MMP-9 mRNA
      expression was accompanied by parallel changes in the gelatinolytic activity of
      the active form of MMP-9, TIMP-1 mRNA expression, and MMP-9 immunoreactivity in
      mesangial cells. In contrast, glomerular MMP-2 mRNA expression and its activity
      increased after the decline of MMP-9. CONCLUSIONS: MMP-9 mRNA was predominantly
      expressed in the glomerulus in normal rat kidneys and MMP-9 was present in the
      mesangium. The MMP-9 mRNA expression increased in the glomerulus 3 to 7 days
      after the induction of anti-GBM glomerulonephritis in WKY rats, in parallel with
      the development of abnormal glomerular histology and injury, suggesting a role of
      MMP-9 in proteolysis of the GBM during glomerulonephritis. MMP-2 may participate
      in the later phase of the nephritis.

PMID- 15480898
TI  - Suppressive effects of Sairei-to on mesangial proliferation in a rat model of
      glomerulonephritis.
AB  - BACKGROUND: Sairei-to (TJ-114) is a Japanese herbal medicine of standardized
      quality, originating from traditional Chinese medicine. In the present in vivo
      study, we investigated the suppressive effects of TJ-114, Shosaiko-to (TJ-9), and
      Saiboku-to (TJ-96) on mesangioproliferative glomerulonephritis (MsPGN) in rats.
      We evaluated the efficacy of these drugs on proteinuria, mesangial cell
      proliferation, and superoxide dismutase (SOD) activity. METHODS: MsPGN was
      induced in Wistar rats by intravenous injection of rabbit anti-rat thymocyte
      serum (ATS). TJ-114, TJ-9, or TJ-96 (500 mg/kg per day) was orally administered
      to the rats in drinking water from the day of ATS injection (day 0) to day 8,
      when rats were killed and kidney specimens were collected. The degree of
      mesangial cell proliferation was evaluated by immunostaining for proliferating
      cell nuclear antigen (PCNA) or macrophage antigen (ED-1). SOD activity in the
      homogenate of the renal cortex was also evaluated. RESULTS: The amount of urinary
      albumin was significantly decreased only in the TJ-114-treated group compared
      with the disease control group ( P < 0.05). The number of PCNA- or ED-1-positive
      cells was significantly decreased in all the treatment groups ( P < 0.05,
      respectively, compared with the disease control group). SOD activity in the renal
      cortex homogenate was significantly augmented in all the treatment groups, most
      markedly in the TJ-96- and TJ-114-treated groups ( P < 0.01, respectively,
      compared with the disease control group). CONCLUSIONS: These results suggest that
      TJ-114 suppresses the proliferation of mesangial cells through its antioxidative
      activity.

PMID- 15480899
TI  - Effect of ureteral obstruction on matrix metalloproteinase-2 in rat renal cortex.
AB  - BACKGROUND: Urinary tract obstruction induces renal damage, including not only
      interstitial fibrosis but also total loss of tissue integrity in the obstructed
      kidney. These processes require degradation and remodeling of the extracellular
      matrix. In the present study, we examined changes in matrix metalloproteinase-2
      (MMP-2), a proteolytic enzyme, in a unilateral ureteral obstruction rat kidney
      model. METHODS AND RESULTS: Gelatin zymography showed that the both mature and
      the immature forms of MMP-2 were increased in the obstructed renal cortex. We
      used real-time reverse transcription polymerase chain reaction (RT-PCR) for the
      quantification of mRNA expression. MMP-2 mRNA was upregulated in the ligated
      kidney and peaked on day 3 after obstruction, while, in contrast, MMP-9 mRNA was
      significantly decreased. Type 1- and type 2-tissue inhibitors of
      metalloproteinase were increased throughout the experimental period. RT-PCR
      showed a concomitant increase in the mRNA expression of membrane type-1 MMP (MT1
      MMP) and extracellular MMP inducer (EMMPRIN). CONCLUSIONS: We conclude that MMP-2
      production in the renal cortex is increased in the early phase of ureteral
      obstruction and could be involved in the damage induced by ureteral obstruction.

PMID- 15480900
TI  - Nilvadipine attenuates mesangial expansion and glomerular hypertrophy in diabetic
      db/db mice, a model for type 2 diabetes.
AB  - BACKGROUND: The renoprotection achieved by angiotensin II blockade in the
      treatment of diabetic nephropathy is well established in both the clinical and
      the experimental settings. In contrast, the therapeutic efficacy of calcium
      channel blockers (CCBs) in the treatment of diabetic nephropathy still remains
      controversial. METHODS: In the present study, we compared the effects of an
      angiotensin-converting enzyme inhibitor, enalapril, and a dihydropyridine CCB,
      nilvadipine, on nephropathy in the db/db mouse, a rodent model of type 2
      diabetes. Male db/db mice were divided into the following three groups at the age
      of 11 weeks, when treatment was started: vehicle, enalapril (10 mg/kg per day),
      and nilvadipine (10 mg/kg per day). Blood pressure, urine, and blood chemistry
      were monitored at the age of 17 and 27 weeks, and kidney samples were obtained at
      29 weeks. Morphological changes were analyzed on periodic acid-Schiff-stained
      sections. Lipid peroxidation in kidney homogenates was measured. RESULTS: Blood
      pressure remained normal and was similar in the three groups until 27 weeks.
      Blood glucose exceeded 300 mg/dl throughout the study in all groups. Reduction of
      microalbuminuria at 27 weeks, compared to the vehicle group, was 37% and 52% in
      the enalapril- and nilvadipine-treated groups, respectively. Increased lipid
      peroxidation was suppressed by 15% and 83% in the enalapril- and nilvadipine
      treated groups, respectively. Glomerular hypertrophy, assessed by cross-sectional
      glomerular area, was significantly suppressed in the nilvadipine group, but not
      in the enalapril group, compared to the vehicle group. CONCLUSIONS: Nilvadipine
      shows a stronger renoprotective effect than enalapril in the db/db mouse,
      independent of the blood-pressure-lowering effect. An antioxidative effect,
      indicated by the reduction in lipid peroxidation, may partly contribute to the
      renoprotection conferred by nilvadipine.

PMID- 15480901
TI  - The effectiveness of steroid therapy for patients with advanced IgA nephropathy
      and impaired renal function.
AB  - BACKGROUND: Recent studies have shown that steroid therapy is effective for IgA
      nephropathy (IgAN) in patients with moderate proteinuria and active histological
      findings. However, the effectiveness of steroid therapy has not been determined
      yet in patients with advanced IgAN and impaired renal function. METHODS: Sixty
      IgAN patients whose creatinine clearance was under 70 ml/min at the time of renal
      biopsy were studied retrospectively. The patients were divided into two groups
      according to treatment: a steroid group ( n = 20) and a nonsteroid group ( n =
      40). The mean age was 39.6 +/- 14.9 years in the steroid group and 40.6 +/- 10.9
      years in the nonsteroid group. The mean follow-up period was 4.5 +/- 2.2 years in
      the steroid group and 4.6 +/- 2.4 years in the nonsteroid group. Patients with
      high proteinuria and high histological activity were treated with prednisolone.
      Clinical and histological findings before treatment and the outcome after
      treatment were analyzed. RESULTS: In the retrospective analysis, the amount of
      urinary protein excretion before treatment tended to be higher in the steroid
      group than in the nonsteroid group, but was not significantly different (2.33 +/-
      1.54 vs 1.39 +/- 1.87 g/day). Histologically, the percentage of patients with
      crescent formation, especially that of cellular or fibrocellular crescents, was
      significantly higher in the steroid group than in the nonsteroid group (17.2 +/-
      15.9% vs 2.3 +/- 4.5%; P < 0.0001). The grades of mesangial cell proliferation
      (1.65 +/- 0.55 vs 1.21 +/- 0.47; P = 0.002) and mesangial matrix increase (1.88
      +/- 0.64 and 1.41 +/- 0.67; P = 0.01) were higher in the steroid group than in
      the nonsteroid group. In the evaluation of the outcome after treatment, the
      amount of urinary protein excretion at 1 year after treatment had significantly
      decreased in the steroid group (before treatment, 2.33 +/- 1.54 g/day; at 1 year,
      1.02 +/- 0.98 g/day; P = 0.003), but the amount remained unchanged in the
      nonsteroid group (before treatment, 1.39 +/- 1.87 g/day; at 1 year, 1.28 +/- 2.19
      g/day). The levels of serum creatinine before treatment and at 1 year after
      treatment were not changed in either of the groups, however, in the nonsteroid
      group, the level at the final observation was significantly higher than the level
      before treatment (2.51 +/- 3.43 vs 1.27 +/- 0.33 mg/dl; P = 0.0219). CONCLUSIONS:
      In the present study, in advanced IgAN patients whose creatinine clearance was
      under 70 ml/min, steroid therapy effectively reduced the amount of proteinuria
      and maintained the serum creatinine level, if the treatment was selectively
      applied to patients with a moderate amount of proteinuria and active glomerular
      lesions such as cellular and fibrocellular crescents, and mesangial cell
      proliferation.

PMID- 15480902
TI  - Clinicopathologic findings relevant to disappearance or relapse of proteinuria
      following corticosteroid treatment in IgA nephropathy patients with proteinuria
      of 0.5 to 2.0 g/day.
AB  - BACKGROUND: We investigated the clinical and pathological findings relevant to
      the efficacy of corticosteroid treatment in IgA nephropathy patients with 0.5 to
      2.0 g/day of proteinuria at the initiation of corticosteroid treatment. METHODS:
      In 27 IgA nephropathy patients who received 2-year prednisolone treatment, we
      analyzed the differences in clinical and pathological parameters (1) between
      patients with and without disappearance of proteinuria (less than 0.15 g/day),
      and (2) between patients with and without relapse of proteinuria (more than 0.5
      g/day) at the end of follow-up. RESULTS: The levels of proteinuria and mesangial
      proliferation at the initiation of prednisolone treatment were significantly
      lower in patients with disappearance of proteinuria at the end of follow-up than
      in those without. The levels of active extraglomerular lesions and
      tubulointerstitial mononuclear cell infiltration and/or fibrosis, and the
      activity index, were significantly higher in patients with relapse of proteinuria
      than in those without. CONCLUSIONS: In IgA nephropathy patients with 0.5 to 2.0
      g/day of proteinuria, disappearance of proteinuria following 2-year prednisolone
      treatment can be expected in patients with less proteinuria and less mesangial
      proliferation at the initiation of the prednisolone treatment. Furthermore,
      active extraglomerular lesions, the activity index, and tubulointerstitial cell
      infiltration and/or fibrosis appear to be more suitable risk markers for relapse
      of proteinuria than the initial levels of proteinuria.

PMID- 15480903
TI  - Prevalence of high fasting plasma glucose and risk of developing end-stage renal
      disease in screened subjects in Okinawa, Japan.
AB  - BACKGROUND: The number of diabetic dialysis patients is increasing worldwide.
      Only a few studies, however, have examined the effect of diabetes mellitus (DM)
      as a risk factor for the development of end-stage renal disease (ESRD) in the
      general population. METHODS: We examined the cumulative incidence of ESRD based
      on the results of community-based mass screening in Okinawa, Japan, performed in
      1993 by the Okinawa General Health Maintenance Association. Fasting plasma
      glucose (FPG) data were available for 78 529 screenees (37 197 men and 41 332
      women). DM was diagnosed when the FPG was 126 mg/dl or more. Screenees who
      developed ESRD by the end of 2000 were identified through the Dialysis Registry,
      Okinawa Dialysis Study. RESULTS: The mean (SD) FPG was 96.5 (22.8) mg/dl, ranging
      from 45 to 577 mg/dl. The prevalence of DM among the screenees was 4089 (5.2%). A
      total of 133 screenees (82 men and 51 women) developed ESRD during the 7.75-year
      study period. The adjusted odds ratio (95% confidence interval [CI]) in the high
      FPG group for the risk of developing ESRD was 3.098 (95% CI, 1.738-5.525; P =
      0.0001), when adjusted for age, sex, systolic blood pressure, diastolic blood
      pressure, body mass index, total cholesterol, triglyceride, hematocrit, serum
      creatinine, hematuria, and proteinuria. CONCLUSIONS: The results of the present
      study indicated that FPG is a significant, independent predictor of ESRD. FPG and
      proteinuria measurements are euqally important in detecting individuals at high
      risk for developing ESRD.

PMID- 15480904
TI  - Reticulocyte hemoglobin content in hemodialysis patients with acute infection.
AB  - BACKGROUND: Reticulocyte hemoglobin content (CHr) has recently become available
      as a direct marker of the iron status in hemodialysis patients undergoing
      recombinant human erythropoietin (rHuEPO) therapy. This study evaluated the
      stability of CHr in hemodialysis patients with acute infectious disease. METHODS:
      We retrospectively selected 22 hemodialysis patients who had acute respiratory
      tract infection and who showed transient elevation of C-reactive protein (CRP),
      and we investigated changes in parameters for erythropoiesis, iron status, and
      inflammation, i.e., hematocrit (Ht), transferrin saturation (TSAT), CHr, serum
      ferritin, and CRP, in the preinfection, infection, and postinfection phases.
      Throughout the observation period, doses of rHuEPO and iron supplements had not
      been changed. We divided the patients into two groups, those who showed a
      decrease in Ht in the infection phase (group 1; n = 12) and those who did not
      show a change in Ht in this phase (group 2; n = 10). We defined the differences
      between the parameters in the preinfection phase and the infection phase as
      Delta, and performed correlation analysis between them. RESULTS: CRP in group 1
      was significantly higher than that in group 2 in the infection phase. In group 1,
      TSAT significantly decreased, from 32.9 +/- 8.8% (preinfection phase) to 16.9 +/-
      5.0% (infection phase), and CHr also significantly decreased, from 33.1 +/- 1.5
      pg to 30.4 +/- 2.0 pg. In group 2, however, although TSAT significantly
      decreased, from 34.8 +/- 4.6% to 27.0 +/- 9.3%, CHr showed no significant change
      (from 33.4 +/- 0.9 pg to 33.0 +/- 1.4 pg). There was a significantly high
      correlation between DeltaHt and DeltaCHr, but there was a low correlation between
      DeltaHt and DeltaTSAT ( r = 0.505; P = 0.0153 versus r = 0.175; P = 0.4420).
      Furthermore, the correlation between DeltaCRP and DeltaCHr was quite high ( r = 
      0.722; P = 0.0001). CONCLUSIONS: TSAT overreacts to inflammation, failing to
      reveal the correct status of available iron for erythropoiesis in acute
      inflammatory disease, but the use of CHr is expected to avoid these
      disadvantages, providing a reliable direct marker of iron status in the acute
      infection phase.

PMID- 15480905
TI  - A male patient with steroid-dependent nephrotic syndrome for 25 years and obesity
      associated focal segmental glomerulosclerosis.
AB  - An obese male patient with steroid-dependent nephrotic syndrome since age 6 years
      had a thirty-third relapse at the age of 29 years. Renal biopsy showed focal
      segmental glomerulosclerosis. Proteinuria disappeared after treatment with
      prednisolone. He went into complete remission and renal function remained normal
      at the age of 31 years. Focal segmental glomerulosclerosis associated with
      obesity was suspected. Long-term follow-up with renal biopsy is necessary in
      obese children with steroid-dependent nephrotic syndrome.

PMID- 15480906
TI  - Steroid-sensitive nephrotic syndrome associated with positive C1q
      immunofluorescence.
AB  - A 21-year-old woman showed heavy proteinuria and edema. A light microscopic study
      of a renal biopsy specimen showed diffuse mild mesangial expansion, with
      borderline mesangial hypercellularity. An immunofluorescence study revealed
      dominant positive staining (3+) of C1q in the glomerular mesangium. Stainings for
      C3, C4, IgG, and IgM were weak or 1+. Staining for IgA was negative. Electron
      dense deposits were present in the mesangial area. There was significant fusion
      of foot processes. There was no serological or clinical evidence of collagen
      disease. She was treated with oral prednisolone (initially, 40 mg/day). The
      proteinuria was alleviated and the patient remains in complete remission. The
      histopathological studies were compatible with C1q nephropathy, although the
      clinical outcome differed in a number of aspects. The clinical picture in the
      current patient appears to represent a very rare phenotype of nephritis.

PMID- 15480907
TI  - Bisalbuminemia in chronic kidney disease.
AB  - Hereditary and acquired bisalbuminemia, in which the serum contains an albumin
      variant differing from albumin A by single amino-acid substitutions, have been
      reported in different races or ethnic groups and in association with various
      pathologic states. The importance of this rare condition in the pathophysiology
      of established diseases is uncertain. We evaluated a 68-year-old woman with
      chronic kidney disease who presented with worsened serum creatinine concentration
      despite lack of dietary or medical changes. Serum protein electrophoresis was
      performed with an automated rapid electrophoresis system. Bisalbuminemia was
      noted as an incidental finding on serum protein electrophoresis. The serum
      creatinine level stabilized with dietary protein restriction and a beta-blocking
      agent/diuretic combination for blood pressure control. Although the possibility
      that some physiologic or pharmacologic substances may not bind to abnormal
      albumin variants as well as they bind to normal albumin should not be discounted,
      the finding of bisalbuminemia did not influence the diagnosis, management,
      course, or prognosis of chronic kidney disease. The role of persistent
      bisalbuminemia in renal disease is uncertain.

PMID- 15480908
TI  - Aneurysmal subarachnoid hemorrhage in a patient with Wegener's granulomatosis.
AB  - A 34-year-old Japanese man admitted to hospital with pneumonia had previously
      undergone surgery for paranasal sinusitis and also for the clipping of an
      aneurysm at the origin of the anterior choroidal artery after subarachnoid
      hemorrhage. Laboratory tests performed at the present admission showed renal
      insufficiency and serological findings of raised proteinase 3 antineutrophil
      cytoplasmic antibody level. A renal biopsy was performed that showed diffuse
      necrotizing glomerulonephritis with fibrocellular crescents. The diagnosis of
      Wegener's granulomatosis(WG) was confirmed on the basis of the clinical picture,
      laboratory findings, and biopsies of renal tissues. The disease responded to
      prednisolone and cyclophosphamide. The association of WG with a ruptured
      intracranial aneurysm is rare and has not previously been confirmed.

PMID- 15480909
TI  - Granulomatous interstitial nephritis due to isolated renal sarcoidosis.
AB  - An 81-year-old woman was admitted to our hospital because of acute exacerbation
      of chronic renal failure. Her 24-h urine protein value was 0.37 g, but neither
      hematuria nor leukocyturia was seen. Renal biopsy specimens showed noncaseating
      granulomas with giant cells in the interstitium. A clinical examination revealed
      no evidence of tuberculosis, fungus, or malignancy. All of the drugs she had been
      taking were discontinued, but her renal function continued to deteriorate. No
      uveitis, erythema nodosum, or common macular skin lesion was seen. A computed
      tomography scan of the thorax and a total-body gallium-67 scan showed no
      abnormalities. The serum lysozyme level was greater than four times above normal.
      Finally, a diagnosis was made, of granulomatous interstitial nephritis due to
      isolated renal sarcoidosis. Treatment was started with 60 mg/day of prednisolone,
      and she had an excellent response. Her serum creatinine level decreased to the
      level shown before the acute exacerbation. It is important to consider renal
      sarcoidosis as a differential diagnosis in patients with severely progressive
      renal failure, because corticosteroid therapy is very effective.

PMID- 15480910
TI  - Adult onset Fanconi syndrome: extensive tubulo-interstitial lesions and
      glomerulopathy in the early stage of Chinese herbs nephropathy.
AB  - A 33-year-old woman was transferred to our hospital with a 5-month history of
      taking Chinese herbal medicine containing aristolochic acid. She presented with
      metabolic acidosis, severe anemia, hypophosphatemia and uric aciduria, and
      generalized aminoaciduria and glycosuria, features which were consistent with the
      clinical manifestations of Fanconi syndrome. Renal biopsy was performed when her
      plasma creatinine was 0.7 mg/dl and creatinine clearance was 46 ml/min per 1.73
      m(2). The renal specimen showed extensive interstitial edema with focal fibrosis,
      tubular atrophy, and focal glomerulopathy, which suggested the presence of
      glomerular endothelial damage or glomerular ischemia. Although steroid therapy
      ameliorated the plasma electrolyte levels, renal failure progressed, and
      hemodialysis therapy was initiated approximately 18 months after the time of
      renal biopsy. This patient demonstrated the early renal lesions of Chinese herbs
      nephropathy in association with various clinical manifestations. The
      characteristic glomerulopathy found in the present patient is considered to be an
      additional renal lesion, leading to the renal failure.

PMID- 15480911
TI  - Patients with rheumatoid arthritis (RA) and proteinuria.

PMID- 15480914
TI  - Substrate regulation of serotonin and dopamine synthesis in Drosophila.
AB  - In Drosophila melanogaster, serotonin (5-hydroxytryptamine, 5-HT) is required for
      both very early non-neuronal developmental events, and in the CNS as a
      neurotransmitter to modulate behavior. 5-HT is synthesized, at least in part, by
      the actions of Drosophila tryptophan-phenylalanine hydroxylase (DTPH), a dual
      function enzyme that hydroxylates both phenylalanine and tryptophan. DTPH is
      expressed in numerous tissues as well as dopaminergic and serotonergic neurons,
      but it does not necessarily function as both enzymes in these tissues.
      Deficiencies in DTPH could affect the production of dopamine and serotonin, and
      thus dopaminergic and serotonergic signaling pathways. In this paper, we show
      that DTPH exhibits differential hydroxylase activity based solely on substrate.
      When DTPH uses phenylalanine as a substrate, regulatory control (end product
      inhibition, decreased PAH activity following phosphorylation, catecholamine
      inhibition) is observed that is not seen when the enzyme uses tryptophan as a
      substrate. These studies suggest that regulation of DTPH enzymatic activity
      occurs, at least in part, through the actions of its substrate.

PMID- 15480915
TI  - Can the glass transition in bulk polymers be modeled by percolation picture?
AB  - Recent observations (Eur. Phys. J. E 9, 135 (2002)) showed that the vitrification
      process, which sets in during the linear bulk methyl methacrylate (MMA)
      polymerization carried out below glass transition temperatures, can be modelled
      by static percolation picture. To generalize this observation for different kind
      of bulk linear or crosslinked polymers not enough data are present in the
      literature. To cover partly this deficit we studied the glass transition of MMA
      and styrene (Sty) crosslinking copolymerization in varying ratios of MMA and Sty.
      Both the fluorescence intensity I and the lifetime tau of pyrene (Py) used as a
      nanosecond in situ fluoroprobe were monitored during the gelation time. Both I
      and tau increase dramatically as a result of the reduced mobility of the probes
      trapped in the "glassy" regions, appearing near the glass transition point. The
      average size of the glassy regions just below, and the strength of the infinite
      network formed upon the connection of the glassy regions above the glass
      transition point tg obey power law relations. The data around tg were interpreted
      on the basis of the percolation theory and we observed that the corresponding
      exponents gamma and beta give static percolation values independent of the
      polymer composition.

PMID- 15480916
TI  - Shear-induced concentration fluctuations and form factor changes in polymer
      solution in the good-solvent regime.
AB  - Small-Angle Scattering from sheared semidilute polymer solution is reported in
      the good-solvent regime, at variance with former light and neutron measurements
      in the theta regime. First, concentration fluctuations are observed: the
      scattering increases noticeably along the flow at low q, but at variance with
      former results for the theta-solvent regime, no demixing is observed at higher
      shear. Here, instead, the effects follow a time-temperature superposition and
      saturate above a Weissenberg number around 5, like the stress which is known to
      present a plateau for these systems. Using the Zero Average Contrast technique,
      we have also measured the form factor, which displays the same saturation effect
      reaching a deformation ratio of the order of 2. These results agree with the
      Convective Constraint Release models (CCR) elaborated in order to predict the
      stress effects in the non-Newtonian regime (Marrucci-Ianniruberto) and their
      extension predicting also the scattering (Likhtman-Milner-McLeish).

PMID- 15480917
TI  - Thickening of a smectic membrane in an evanescent X-ray beam.
AB  - We report an unusual thickening of smectic membranes under the influence of X-ray
      irradiation below the critical angle. In the case of a four-layer film the
      thickness was found to grow at the footprint of the beam, reaching within minutes
      tens of layers. The effect is attributed to the localized energy dissipation of
      the evanescent wave. The "island" thus created is not connected to the meniscus
      and after the beam is switched off the film returns to its original state. A
      possible explanation is given in terms of a local disrupture of the tension of
      the smectic membrane.

PMID- 15480918
TI  - Exact lattice calculations of dispersion coefficients in the presence of external
      fields and obstacles.
AB  - We present a study of the field-dependent dispersion coefficient of point-like
      particles in various 2D overdamped systems with obstructions (periodic,
      percolating, and trapping distributions of obstacles). These calculations profit
      from the synthesis of a newly proposed Monte Carlo algorithm--the first such
      algorithm that correctly reproduces the free dispersion coefficient in the
      presence of finite external fields--and an asymptotically exact calculation
      technique. The resulting method efficiently produces algebraic and numerical
      results without the need to actually perform Monte Carlo simulations. When
      compared to such simulations, our exact method features a negligible
      computational cost and exponentially small errors. Utilizing the power of this
      numerical method, we engage in comprehensive parametric analysis of several model
      systems, revealing very subtle effects that would otherwise be swamped by
      statistical errors or incur prohibitive computational costs. The unified
      framework presented here serves as a template for further applications of lattice
      random-walk models of biased diffusion.

PMID- 15480919
TI  - Stepwise unfolding of collapsed polymers.
AB  - Motivated by recent experimental data on DNA stretching in presence of polyvalent
      counterions, we study the force-induced unfolding of a homopolymer on and off
      lattice. In the fixed force ensemble the globule unravels via a series of steps
      due to surface effects which play an important role for finite-size chains. This
      holds both for flexible and stiff polymers. We discuss in a qualitative way how
      this result may impact on the interpretation of DNA stretching experiments
      showing peaks in the characteristic curves, by extracting from the raw data the
      corresponding elongation- versus-force characteristic curves. Furthermore,
      approximate analytical and numerical calculations, valid in a quasi-equilibrium
      fixed stretch ensemble, and if the initial low-temperature state is ordered in a
      spool, show that the average force versus elongation displays peaks related to
      the geometry of the initial configuration. We finally argue how the proposed
      mechanisms identified for the arising of peaks may couple in the experiments, and
      comment on the role of dynamic effects.

PMID- 15480920
TI  - Pharmacoeconomic evaluation of immunoglobulin treatment in patients with antibody
      deficiencies from the perspective of the German statutory health insurance.
AB  - Primary antibody deficiencies are the most common forms of primary
      immunodeficiencies. Substitution therapy with polyvalent immunoglobulins has been
      established as the standard therapy for antibody deficiencies for several
      decades. Until now mainly intravenous immunoglobulins (IVIG) have been used in
      Germany, and the majority of patients receive treatment in hospital outpatient
      clinics. In recent years subcutaneous administration of immunoglobulins (SCIG)
      has been developed which is administered as home self-infusion. Studies indicate
      no significant differences in immunoglobulin substitution therapy between SCIG
      and IVIG concerning outcome. We carried out a cost-minimization analysis to
      compare the two treatment alternatives in Germany. Under base case assumptions
      the treatment with SCIG is cost saving from the perspective of the German
      statutory health insurance. The main cost drivers are IVIG and SCIG; the
      incremental cost of SCIG compared to IVIG is most sensitive to changes in the
      immunoglobulin price and changes in the body weight of the patient.

PMID- 15480922
TI  - Cellular expression of C3 and C4 photosynthetic enzymes in the amphibious sedge
      Eleocharis retroflexa ssp. chaetaria.
AB  - The amphibious leafless sedge Eleocharis retroflexa ssp. chaetaria expresses C(4)
      like biochemical characteristics in both the terrestrial and submerged forms.
      Culms of the terrestrial form have Kranz anatomy, whereas those of the submerged
      form have Kranz-like anatomy combined with anatomical features of aquatic plant
      leaves. We examined the immunolocalization of C(3) and C(4) enzymes in culms of
      the two forms. In both forms, phosphoenolpyruvate carboxylase; pyruvate, Pi
      dikinase; and NAD-malic enzyme were compartmentalized between the mesophyll (M)
      and Kranz cells, but their levels were somewhat reduced in the submerged form. In
      the terrestrial form, ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco)
      occurred mainly in the Kranz cells, and weakly in the M chloroplasts. In the
      submerged form, the rubisco occurred at higher levels in the M cells than in the
      terrestrial form. In both forms, the C(4) pattern of enzyme expression was
      clearer in the M cells adjacent to Kranz cells than in distant M cells. During
      the transition from terrestrial to submerged conditions, the enzyme expression
      pattern changed in submerged mature culms that had been formed in air before
      submergence, and matched that in culms newly developed underwater. It seems that
      effects of both environmental and developmental factors overlap in the C(4)
      pattern expression in this plant.

PMID- 15480923
TI  - 1st Joint Meeting of the European Federation of Autonomic Societies (EFAS) &
      American Autonomic Society AAS). Amsterdam, The Netherlands , October 20-23,
      2004. Abstracts.

PMID- 15480925
TI  - Syncope-past, present and future.

PMID- 15480926
TI  - Pathophysiology of syncope.
AB  - Syncope or near-syncope is a not uncommon effect of gravitational or other
      stresses and it occurs when cerebral blood flow falls to below about half the
      normal value. It is not necessarily abnormal, and individuals who are usually
      asymptomatic show the same reaction if a stress is sufficiently great to result
      in hypotension. Blood pressure is regulated mainly by baroreceptor reflexes by
      their control of vascular resistance and heart rate. The ability to vasoconstrict
      powerfully is important in resisting syncope; heart rate responses are of much
      less physiological significance. The intriguing unanswered question is what
      suddenly changes vasoconstriction and tachycardia to vasodilatation and
      bradycardia. It is now known not to be due to stimulation of cardiac receptors
      and some cerebral signal is more probable. People are more likely to faint when
      upright, motionless, warm, following meals, dehydrated or emotionally stressed,
      and these factors may be involved in some reflex syncopes including micturition
      and defaecation syncopes. Plasma volume is of considerable importance and
      increasing this by interventions such as salt loading, exercise training, and
      even sleeping with the bed head raised can often be of clinical benefit.

PMID- 15480927
TI  - Exercise related syncope, when it's not the heart.
AB  - Syncope or pre-syncope in association with physical exercise may be the first
      indication of a dangerous underlying cardiovascular condition. Thus, the
      diagnostic workup of patients presenting with exercise-related syncope must
      include assessment of the risk for acute cardiac death. When potentially lethal
      conditions have been ruled out, several hypotensive syndromes that are associated
      with exercise should be considered. This review aims to give a concise overview
      of several forms of exercise- related functional hypotensive syndromes causing
      syncope, including the physiology of post-exercise hypotension. The focus is on
      underlying mechanisms, clinical considerations, and outlining treatment
      strategies for these syndromes.

PMID- 15480928
TI  - Diagnostic value of history taking in reflex syncope.
AB  - The medical history, in combination with the physical examination and a 12-lead
      electrocardiogram, plays a key role in the diagnosis and risk stratification of
      patients with syncope. However, diagnostic clinical criteria are not uniformly
      applied. In older studies, the diagnostic criteria for vasovagal or reflex
      syncope often included typical precipitating events and warning symptoms. More
      recent studies have documented that a variety of unrecognized stressors can
      trigger reflex syncope and that warning signs and symptoms may be minimal. A
      characteristic medical history (a trigger and/or prodromi) is enough to diagnose
      reflex syncope if the risk for a cardiac cause of syncope is low (e. g. patients
      < 65 yrs, without a history of heart disease and no ECG abnormalities). In
      elderly subjects with a higher risk of cardiac syncope, the yield of the medical
      history is lower. However, a prospective study of the value of the medical
      history for the diagnosis of syncope with long-term follow-up has not been
      performed.

PMID- 15480929
TI  - Defining and classifying syncope.
AB  - There is no widely adopted definition or classification of syncope and related
      disorders. This lack of uniformity harms patient care, research, and medical
      education. In this article, syncope is defined as a form of transient loss of
      consciousness (TLOC) due to cerebral hypoperfusion. Differences between syncope
      and other causes of TLOC such as epilepsy, and disorders mimicking TLOC are
      described. A pathophysiological classification of syncope is proposed.

PMID- 15480930
TI  - Role of autonomic evaluation in the diagnosis and management of syncope.
AB  - There are many causes of syncope that include neurological (autonomic and non
      autonomic), cardiac and psychiatric causes, amongst others. Disorders of the
      autonomic nervous system, either intermittent or fixed, are increasingly
      recognised as contributing to a large proportion of syncope. However, the
      majority of guidelines focus on cardiological and neurological evaluation in
      these disorders. In this overview we focus specifically on the role of autonomic
      evaluation. This has dual purposes; to aid the diagnosis and cause of syncope,
      and furthermore to provide information to understand the pathophysiological basis
      of syncope and thus improve management of such disorders.

PMID- 15480931
TI  - The use of monitoring strategies in patients with unexplained syncope--role of
      the external and implantable loop recorder.
AB  - Syncope is a complex clinical syndrome with multiple etiologies that can be very
      difficult to diagnose. The major obstacles to diagnosis are the periodic and
      unpredictable nature of events and the high spontaneous remission rate. Short
      term electrocardiographic monitoring is often unproductive in patients when
      initial non-invasive testing is negative, particularly when a paroxysmal
      arrhythmia is suspected. The external and implantable loop recorders extend the
      ability to monitor cardiac patients, enhancing the diagnostic yield to as high as
      85% in difficult to diagnose syncope. Several recent studies suggest that
      prolonged monitoring with an implantable loop recorder has a role in patients
      with syncope and conduction disturbances, negative tilt testing, unexplained
      seizures and may be superior to conventional testing with tilt and
      electrophysiologic studies in selected patients.

PMID- 15480932
TI  - Nonpharmacological treatment of reflex syncope.
AB  - Reflex syncope is a common medical problem. Vasovagal reflex syncope is the most
      frequent form. Although the prognosis of the disorder is excellent, it may impose
      substantial changes in life style and cause profound psychological distress.
      Thus, management of this disorder is an important issue. This chapter, based on a
      review of the literature and the authors' clinical experience, encompasses the
      non-pharmacological measures used in the management of reflex syncope. The
      cornerstone of the non-pharmacological management of patients with reflex syncope
      is education and reassurance regarding the benign nature of the condition.
      Patients should be instructed to avoid potential triggers. A tilt table test can
      be employed to teach the patient to recognize early premonitory symptoms. There
      are several physical maneuvers (e. g., leg crossing, muscle tensing and
      squatting) that are effective in combating orthostatic intolerance. For the
      majority of patients this approach is adequate. Patients with frequent attacks of
      reflex syncope are advised to increase their dietary salt intake. Exercise
      training also increases orthostatic tolerance. In highly motivated patients with
      recurrent syncope, raising the head of the bed to permit gravitational exposure
      during sleep and prolonged periods of enforced maintenance of the upright posture
      (tilt-training) can be considered. Preliminary data suggest that water drinking
      may improve orthostatic tolerance. Abdominal belts may also be effective in
      highly symptomatic subjects with reflex syncope.

PMID- 15480933
TI  - Pharmacological treatment of reflex syncope.
AB  - Patient education, identification of possible triggers of syncope and reassurance
      are a central feature of the management of patients with reflex syncope. Patients
      should be advised as to the importance of adequate hydration and taught physical
      countermaneuvers to enhance cardiac venous return. These maneuvers are sufficient
      for most patients, however, for a small number of patients who continue to have
      recurrent syncopal events, pharmacological intervention may be considered. Volume
      expansion can be enhanced with salt and fludrocortisone. Agents from diverse
      pharmacological classes have been used to attenuate the reflex response, enhance
      vasoconstriction and attenuate vagal outflow. Alpha adrenoreceptor agonists,
      anticholinergic agents, theophylline, beta adrenoreceptor antagonists, serotonin
      reuptake inhibitors and disopyramide are the most widely studied. None of these
      agents has shown a consistent therapeutic benefit in clinical trials.

PMID- 15480934
TI  - Permanent cardiac pacing as primary therapy for neurocardiogenic (reflex)
      syncope.
AB  - Recurrent reflex (or neurocardiogenic) syncope is a common clinical problem.
      Pacemaker therapy has been advocated as a potential therapy in severe or drug
      refractory cases of reflex syncope, while others have suggested that it may
      provide a benefit if employed as a primary therapeutic modality. The following
      paper reviews the concepts behind pacemaker therapy for reflex syncope and the
      results of various clinical trials that have evaluated its potential utility as a
      primary therapeutic modality.

PMID- 15480936
TI  - Syncope: a clinically guided diagnostic algorithm.
AB  - The initial evaluation of a patient with syncope should include a thorough
      clinical history, physical examination and 12 lead electrocardiogram (ECG). The
      history is the best diagnostic tool. Clinical findings guide further testing.
      Patients with syncope and heart disease require echocardiography, Holter
      monitoring or exercise testing. The tilt test and carotid sinus massage are
      useful to reproduce reflex syncope. An insertable subcutaneous loop recorder can
      provide prolonged ECG monitoring.

PMID- 15480935
TI  - The management of patients with carotid sinus syndrome: is pacing the answer?
AB  - Carotid sinus syndrome (CSS) is an under recognized cause of recurrent
      unexplained syncope and potentially of recurrent falls in the elderly. The
      mechanisms that lead to syncope in patients with CSS remain debated. However,
      evidence for both peripheral and central alterations have been recently reported.
      The diagnosis of CSS is challenging and a high clinical suspicion is usually
      needed to make the diagnosis. Clinical presentation may be typical and
      characterized by a clear association between accidental manipulation of the
      carotid sinus and the presentation of syncope. On the other hand, recurrent
      unexplained syncope and unexplained falls may be the clinical presentation of
      patients with CSS without a specific trigger. Carotid sinus hypersensitivity
      documented by carotid sinus massage (CSM) may be the only finding indicating the
      possibility of CSS as the cause of syncope. In older patients with recurrent
      unexplained syncope and a negative diagnostic work-up, carotid sinus massage both
      in the supine and upright positions is recommended. CSS may present primarily as
      a cardioinhibitory response or a true vasodepressor response. Therapy should
      address any underlying pathology if present, and be directed to either prevent
      cardioinhibition, vasodepression or both alterations. A variety of medical
      therapies have been used with unclear effects. No appropriately designed
      controlled clinical trials have been performed comparing pacing with medical
      therapy. Nonetheless, available information indicates that pacing may have a
      strong beneficial effect and prevents recurrence of syncope in patients with CSS.
      The present paper critically reviews the latest insights in the pathophysiology,
      diagnosis and management of CSS.

PMID- 15480939
TI  - Optimization of Streptomyces peucetius var. caesius N47 cultivation and epsilon
      rhodomycinone production using experimental designs and response surface methods.
AB  - Streptomyces peucetius var. caesius is an aerobic bacterium that produces
      doxorubicin as a secondary metabolite. A mixture design was applied for the
      screening of suitable complex medium components in the cultivation of S.
      peucetius var. caesius N47, which is an epsilon-rhodomycinone-accumulating mutant
      strain. epsilon-Rhodomycinone is a non-glycosylated precursor of doxorubicin.
      Best growth results were obtained with soy peptone and beef extract. A central
      composite face-centered (CCF) experimental design was constructed for the
      investigation of pH, temperature and dissolved oxygen (DO) effects on the
      cultivation growth phase. Another CCF was applied to the production phase to
      investigate the effects of aeration, pH, temperature and stirring rate on epsilon
      rhodomycinone production. An increase in cultivation temperature increased both
      cell growth and glucose consumption rate. Best epsilon-rhodomycinone
      productivities were obtained in temperatures around 30 degrees C. DO control
      increased all growth phase responses, but aeration in the production phase
      coupled with pH decrease resulted in rapid epsilon-rhodomycinone decay in the
      medium. In non-aerated production phases a pH change resulted in better
      productivity than in experiments without pH change. A pH increase with a
      temperature decrease seemed most beneficial for productivity. This implies that
      dynamic control strategies in batch production of epsilon-rhodomycinone could
      increase the overall process productivity.

PMID- 15480937
TI  - Epidemiology of reflex syncope.
AB  - Cost-effective diagnostic approaches to reflex syncope require knowledge of its
      frequency and causes in different age groups. For this purpose we reviewed the
      available literature dealing with the epidemiology of reflex syncope. The
      incidence pattern of reflex syncope in the general population and general
      practice is bimodal with peaks in teenagers and in the elderly. In the young
      almost all cases of transient loss of consciousness are due to reflex syncope.
      The life-time cumulative incidence in young females ( congruent with 50 %) is
      about twice as high as in males ( congruent with 25 %). In the elderly, cardiac
      causes, orthostatic and postprandial hypotension, and the effects of medications
      are common, whereas typical vasovagal syncope is less frequent. In emergency
      departments, cardiac causes and orthostatic hypotension are more frequent
      especially in elderly subjects. Reflex syncope, however, remains the most common
      cause of syncope, but all-cause mortality in subjects with reflex syncope is not
      higher than in the general population. This knowledge about the epidemiology of
      reflex syncope can serve as a benchmark to develop cost-effective diagnostic
      approaches.

PMID- 15480940
TI  - A simulation study comparing the impact of experimental error on the performance
      of experimental designs and artificial neural networks used for process
      screening.
AB  - Many variables and their interactions can affect a biotechnological process.
      Testing a large number of variables and all their possible interactions is a
      cumbersome task and its cost can be prohibitive. Several screening strategies,
      with a relatively low number of experiments, can be used to find which variables
      have the largest impact on the process and estimate the magnitude of their
      effect. One approach for process screening is the use of experimental designs,
      among which fractional factorial and Plackett-Burman designs are frequent
      choices. Other screening strategies involve the use of artificial neural networks
      (ANNs). The advantage of ANNs is that they have fewer assumptions than
      experimental designs, but they render black-box models (i.e., little information
      can be extracted about the process mechanics). In this paper, we simulate a
      biotechnological process (fed-batch growth of baker's yeast) to analyze and
      compare the effect of random experimental errors of different magnitudes and
      statistical distributions on experimental designs and ANNs. Except for the
      situation in which the error has a normal distribution and the standard deviation
      is constant, it was not possible to determine a clear-cut rule for favoring one
      screening strategy over the other. Instead, we found that the data can be better
      analyzed using both strategies simultaneously.

PMID- 15480941
TI  - Behavior of microbial communities developed in the presence/reduced level of
      soluble microbial products.
AB  - Soluble microbial products (SMP) are organics produced by microorganisms as they
      degrade substrates. The available literature does not reveal how SMP affect and
      regulate microbial activities. In this study, we monitored variations in pH,
      dissolved oxygen concentration, soluble biological and chemical oxygen demands
      (sBOD5 and sCOD) as a measure of microbial activity in synthetic wastewater.
      Aerobic degradation tests were carried out under the following conditions:
      aeration, 1,500 cm3 /min; initial sBOD5, 515+/-5 mg/l; initial sCOD, 859+/-6
      mg/l; initial biomass concentration (defined as mixed liquor suspended solids),
      1,200+/-25 mg/l; sludge retention time, 24 h; and temperature, 20+/-1 degrees C.
      The study involved non-acclimated biomass (R0 flora), biomass developed in the
      presence of SMP (R1 flora), and biomass developed in reduced level of SMP (R2
      flora). We also determined which of these flora produced more refractory SMP. The
      results showed that R2 flora utilized the synthetic feed more quickly, and
      produced less refractory organic matter than R0 and R1 flora. The production of
      more refractory organics by R0 and R1 flora shows that not all the biomass was
      active. R1 flora degraded the substrates irregularly, suggesting that some
      microbes were dependent on the metabolic products of those that could utilize the
      feed components. These results show that production of SMP also depends on the
      prior substrates and on the ability of the flora to respond to changes in
      substrate composition.

PMID- 15480942
TI  - Enhancing of erythromycin production by Saccharopolyspora erythraea with common
      and uncommon oils.
AB  - The enhancing effect of various concentrations of 18 oils and a silicon antifoam
      agent on erythromycin production by Saccharopolyspora erythraea was evaluated in
      a complex medium containing soybean flour and dextrin as the main substrates. The
      oils used consisted of sunflower, pistachio, cottonseed, melon seed, water melon
      seed, lard, corn, olive, soybean, hazelnut, rapeseed, sesame, shark, safflower,
      coconut, walnut, black cherry kernel and grape seed oils. The biomass,
      erythromycin, dextrin and oil concentrations and the pH value were measured.
      Also, the kinds and frequencies of fatty acids in the oils were determined. The
      productivity of erythromycin in the oil-containing media was higher than that of
      the control medium. However, oil was not suitable as a main carbon source for
      erythromycin production by S. erythraea. The highest titer of erythromycin was
      produced in medium containing 55 g/l black cherry kernel oil (4.5 g/l). The
      titers of erythromycin in the other media were also recorded, with this result:
      black cherry kernel > water melon seed > melon seed > walnut > rapeseed > soybean
      > (corn = sesame) > (olive = pistachio = lard = sunflower) > (hazelnut = cotton
      seed) > grape seed > (shark = safflower = coconut). In media containing various
      oils, the hyphae of S. erythraea were longer and remained in a vegetative form
      after 8 days, while in the control medium, spores were formed and hyphae were
      lysed.

PMID- 15480943
TI  - Reunion displays in captive male brown capuchins (Cebus apella).
AB  - Separation and subsequent reintroduction of brown capuchins (Cebus apella) can
      lead to reunion displays during which individuals will embrace and emit high
      pitched, loud vocalizations. These displays were investigated in three male
      capuchins: two adults and one juvenile. These subjects were part of a larger
      captive social group held at the Capuchin Laboratory, Hiram College, OH, USA. We
      hypothesized that males would engage in reunion displays following separation
      regardless of the order of reintroduction, as evidence of an affiliative bond
      judged by concurrent social behavior. Sixty separations were conducted as part of
      weekly husbandry over a period of 13 months. Occurrence of reunion displays
      between the males was recorded with the initiator also noted. Reunion displays
      among males were found to occur only between the juvenile and alpha male, and all
      displays were initiated by the juvenile. Displays were highly influenced by the
      order of reintroduction. We suggest that reunion displays operate to reaffirm
      social relationships, particularly during situations of social tension.

PMID- 15480944
TI  - Volumetric analysis of mice lungs in a clinical magnetic resonance imaging
      scanner.
AB  - Small animal models are widely used to study various pathologies. Magnetic
      resonance imaging (MRI) allows investigation of these animals in a non-invasive
      way. Therefore, the aim of our study was to develop and evaluate a low-cost
      approach to measure lung volumes in small animal MRI using a clinical scanner and
      a specially designed RF coil. Five mice (three of an established emphysema model
      and two controls) were investigated in a 1.0-T clinical scanner using a specially
      built small animal saddle coil and three different three-dimensional sequences;
      overall imaging time was approximately 16 min. Lung volumes were calculated from
      these images using an interactive watershed transform algorithm for semi
      automatic image segmentation. The gold standard for the volume measurement was
      water displacement after surgical explantation. MRI measured volumes correlated
      significantly with ex vivo measurements on the explanted lungs (r = 0.99 to 0.89;
      p < 0.05). Mean lung volume in emphysema model mice was larger than in controls.
      High-resolution, small animal MRI using a clinical scanner is feasible for
      volumetric analysis and provides an alternative to a dedicated small animal
      scanner.

PMID- 15480946
TI  - General view of orthoses.
AB  - Braces and/or orthoses are one of the useful tools for treating stroke patients.
      Orthoses work to substitute for mechanical and/or functional impairments. This
      article discusses what orthoses are, what the purposes of orthoses are, how the
      orthoses are made, how long it takes to make the braces, and who makes them.
      Although braces and orthoses are heavier and tighter than usual shoes and
      clothing, they help patients a great deal in performing activities of daily
      living.

PMID- 15480947
TI  - Short leg brace and stroke rehabilitation.
AB  - OBJECTIVE: We looked for the patients who were treated by short leg brace (SLB)
      in our hospital for the effects on the treatment of stroke. METHOD: Patients
      admitted to our hospital for the purposes of rehabilitation of stroke and had SLB
      prescription from October 2001 to October 2003 were investigated. A total of 20
      patients (19 men, 11 women) were investigated in this study. Average age was 60.8
      +/- 8.60 years old. Diagnoses were cerebral hemorrhage (12), brain infarction
      (7), and subarachnoid hemorrage (2). There was right hemiparesis in 15 patients,
      and left hemiparesis in 15. Activities of daily living (ADLs) were evaluated by
      FIM at admission and at discharge. The difference between these FIM scores was
      recorded as DeltaFIM. The levels of ambulation were classified into "need help,"
      "need observation," and "self-sufficient." At the same time, the need for walking
      aid was recorded. To determine the effects of SLB, all the patients were checked
      for period of ambulation with cane to the prescription of SLB (period A), period
      of completion of SLB to acquirement of final walking ability (period B), and
      Brunnstrom recovery stage for the evaluation of motor recovery. Finally, the
      level of paralysis, the periods of A and B, ADL assessments, and final ambulation
      level were investigated. RESULTS: At the time of admisison, the average FIM was
      73.9 +/- 24.2; average FIM at time of discharge was 98.2 +/- 21.7. DeltaFIM was
      24.3 +/- 21.7. The period A was 37.9 +/- 22.7 days and the period B was 36.8 +/-
      24.6 days. The final gait performance was need help, 6; need supervision, 11; and
      self-sufficient, 13. When we compared Brunnstrom recovery stage III and IV
      patients and Brunnstrom recovery stage II patients, stage II patients had a
      longer period A.

PMID- 15480945
TI  - Dynamic contrast-enhanced MRI using macromolecular contrast media for monitoring
      the response to isolated limb perfusion in experimental soft-tissue sarcomas.
AB  - The objective of this study was to evaluate the potential of dynamic contrast
      enhanced MRI for quantitative characterization of tumor microvessels and to
      assess the microvascular changes in response to isolated limb perfusion with TNF
      alpha and melphalan. Dynamic contrast-enhanced MRI was performed in an
      experimental cancer model, using a macromolecular contrast medium, albumin-(Gd
      DTPA)45. Small fragments of BN 175, a soft-tissue sarcoma, were implanted in 11
      brown Norway (BN) rats. Animals were assigned randomly to a control (Haemaccel)
      or drug-treated group (TNF-alpha/melphalan). MRI was performed at baseline and 24
      h after ILP. The transendothelial permeability (K(PS)) and the fractional plasma
      volume (fPV) were estimated from the kinetic analysis of MR data using a two
      compartment bi-directional model. K(PS) and fPV decreased significantly in the
      drug-treated group compared to baseline (p<0.05). In addition, K(PS) post therapy
      was significantly lower (p<0.05) in the drug-treated group than in the control
      group. There was no significant difference in fPV between the drug-treated and
      the control group after therapy. Tumor microvascular changes in response to
      isolated limb perfusion can be determined after 24 h by dynamic contrast-enhanced
      MRI. The data obtained in this experimental model suggest possible applications
      in the clinical setting, using the appropriate MR contrast agents.

PMID- 15480948
TI  - Stroke rehabilitation and long leg brace.
AB  - Although a short leg brace (SLB) is mainly used for stroke rehabilitation, we
      should also remember the value of a long leg brace (LLB). The indications for LLB
      are discussed. For example, a LLB provides stability for the knee. The LLB can be
      used in any situation that creates instability for the knee. The practice of a
      155-bed medium-sized rehabilitation hospital in Japan is investigated regarding
      stroke rehabilitation and the LLB from October 2001 to October 2003. The LLB was
      prescribed to 12 patients. If the patients made good progress, the LLB was
      converted to an SLB. The period of conversion from LLB to SLB shows the
      improvement of the conditions. Patients were divided into three groups according
      to the period of the conversion: less than 14 days, more than 15 days, and no
      conversion. Comparing the FIM points, there are more points for patients whose
      brace is converted in less than 14 days but there is a greater improvement in FIM
      points when the brace is converted in more than 14 days. It is advised that the
      patients who have the worse conditions should have the LLB earlier because then
      these patients can concentrate on their rehabilitation program and are not
      disturbed by the conversion of the brace.

PMID- 15480949
TI  - Therapeutic orthosis and electrical stimulation for upper extremity hemiplegia
      after stroke: a review of effectiveness based on evidence.
AB  - Upper extremity hemiplegia after stroke is common and disabling. Apart from
      conventional physical and occupational therapy, a number of additional approaches
      that use devices such as orthoses, prostheses, electrical stimulation, and robots
      have been introduced. The purpose of this review was to assess the clinical
      efficacy of such devices used for the affected upper extremities of acute,
      subacute, and chronic stroke patients. Assessments of their effectiveness and
      recommendations were based on the weight of published scientific evidence. The
      amount of evidence with respect to hand splints and shoulder slings is limited.
      Further study with a well-designed randomized controlled trial (RCT) is required
      to investigate accurately their short- and long-term efficacy. A number of
      studies suggested that the use of electrical stimulation for reducing shoulder
      subluxation or improving the function of wrist and finger extensors is effective
      during or shortly after the daily treatment period. The robotic approach to
      hemiplegic upper extremities appears to be a novel therapeutic strategy that may
      help improve hand and arm function. However, the longer term effectiveness after
      discontinuation as well as the motor recovery mechanism of electrical stimulation
      or robotic devices remains unclear. More research is needed to determine the
      evidence-based effectiveness of electrical stimulation or other devices for
      stroke survivors.

PMID- 15480950
TI  - Leg orthosis treatment for a patient with left parietal foot amputation and right
      hemiplegia.
AB  - In developing a training program from standing to walking for a patient with a
      left parietal foot amputation and right hemiplegia, we found that the leg
      orthosis was effective in allowing the patient to regain the balancing ability
      when standing. The leg orthosis had practical effects on increasing walking
      distance.

PMID- 15480951
TI  - Development and validation of the stroke knowledge test.
AB  - PURPOSE: The purpose of this study was to develop a measure of stroke knowledge
      (the Stroke Knowledge Test [SKT]) using a systematic test construction process
      and to investigate the psychometric properties of this test. There are relatively
      few published measures of stroke knowledge, and, of those that exist, relatively
      little is documented about test construction or psychometric properties. Such
      tests are important for evaluation of stroke education programs. METHOD: Test
      construction involved systematic generation of pilot test items, expert review of
      pilot items, and calculation of pilot item properties. After final item
      selection, two experiments were conducted to determine if the SKT was sensitive
      to varying levels of stroke knowledge and to estimate the reliability of the
      test. RESULTS: The final version of the test included 20 items with good content
      coverage, acceptable item properties, and positive expert review ratings. Results
      from psychometric investigations suggest that SKT has relatively good reliability
      (internal consistency and test-retest reliability) and construct validity (i.e.,
      SKT scores significantly increased after stroke education [cf. nonstroke
      education], and community-dwelling older adults who had a relative with stroke
      [and more prior exposure to stroke information] scored higher on the SKT than
      those without a stroke relative). CONCLUSION: Findings provide preliminary
      support for the SKT as a valid and reliable tool for assessing stroke knowledge.
      The SKT may be used to identify individual information needs of stroke survivors
      and their caregivers or as a tool to evaluate group- or community-based stroke
      education programs.

PMID- 15480952
TI  - Stroke education materials on the World Wide Web: an evaluation of their quality
      and suitability.
AB  - Web-based information is a valuable resource for people affected by stroke,
      however its accuracy and quality have been questioned. In this study, 30 stroke
      education websites were reviewed using accountability, readability, and
      reliability measures. Fifteen consumers and 11 health professionals evaluated six
      sites in terms of their design, content, and ease of use. The websites mostly met
      accountability criteria, but their reliability scores were low and their
      readability was high. Consumers' opinions were consistently higher than health
      professionals', but scores indicated their preferences for particular websites,
      especially in terms of design. The importance of considering consumers'
      preferences when designing and recommending websites is highlighted.

PMID- 15480953
TI  - Evaluating unilateral spatial neglect post stroke: working your way through the
      maze of assessment choices.
AB  - This study identified, using a comprehensive review of the literature, 62
      standardized and nonstandardized assessment tools that exist to evaluate
      unilateral spatial neglect (USN). Each standardized tool was critically appraised
      according to its purpose (hemispace assessed), psychometric properties, and
      client appropriateness. The findings on the 28 standardized tools were compiled
      into a USN Assessment Summary Guide to facilitate clinical decision-making
      regarding the standardized USN assessments that are appropriate for specific
      clients at different phases of their recovery post stroke.

PMID- 15480954
TI  - Factors affecting the adjustment to disability for new immigrants.
AB  - Factors such as self-esteem, social support, and perceived social discrimination
      are associated with the acceptance of disability. A new immigrant may face unique
      barriers to health care, including cultural differences between the patient and
      provider, language/communication issues, and discrimination. However, little
      research is available that identifies barriers specific to new immigrants
      relating to disability. This is an exploratory descriptive pilot study using a
      phenomenological approach. The investigator interviewed two "new" immigrants with
      an acquired disability. A "new" immigrant is defined as an individual who was
      born outside of the United States, whose parents were born outside of the United
      States, and who relocated across international borders to live in this country.
      The participants reported on perceived barriers to the adjustment to a
      disability. Strategies to consider in the care of the immigrant patient are
      described.

PMID- 15480957
TI  - Fever and rash complicating osteomyelitis.

PMID- 15480958
TI  - The global mortality of infectious and parasitic diseases in children.
AB  - Although considerable advances in the reduction of global child morbidity and
      mortality have been made since 1970, when more than 17 million children died, the
      burden of child mortality is still intolerably high today. An estimated 10.5
      million younger than the age of 5 years died in the year 2002 from largely
      preventable diseases, such as those having infectious, parasitic, and perinatal
      causes. The reductions in rates of mortality observed did not take place
      uniformly across time and regions of the world, but the success stories in
      developing countries demonstrate clearly that low mortality levels are achievable
      in those settings. If the whole world came to share the current child mortality
      experience of Northern European countries, more than 10 million deaths of
      children could be prevented each year. This work aims to answer the questions
      concerning where and why so many of the world's children still succumb to largely
      preventable causes.

PMID- 15480959
TI  - Current issues in global immunizations.

PMID- 15480960
TI  - Prevention of infectious diseases among international pediatric travelers:
      considerations for clinicians.
AB  - An estimated 1.9 million children travel overseas annually. Infectious disease
      risks associated with international travel are diverse and depend on the
      destination, planned activities, and baseline medical history. Children have
      special needs and vulnerabilities that should be addressed when preparing for
      travel abroad. Children should have a pretravel health assessment that includes
      recommendations for both routine and special travel-related vaccination; malaria
      chemoprophylaxis, if indicated; and prevention counseling regarding insect and
      animal exposures, food and water safety, and avoiding injuries. Special
      consideration should be given to children with chronic diseases. Families should
      be given anticipatory guidance for management of potential illnesses and
      information about the location of medical resources overseas.

PMID- 15480961
TI  - Tuberculosis in children: considerations for children from developing countries.
AB  - Although accurate data are scarce for children, tuberculosis (TB) represents one
      of the most common infectious causes of morbidity and mortality worldwide. TB
      case rates have declined among children in the United States in the last decade,
      but they remain high among children from low-income countries and racial or
      ethnic minorities. Establishing the definitive diagnosis of TB in a child remains
      difficult and frequently relies on a constellation of history, clinical findings,
      and bacteriology. Recently, updated national and international treatment
      recommendations have been published. Contact investigation and treatment using
      directly observed therapy are important components of the optimal case detection
      and management of TB in children.

PMID- 15480962
TI  - Acute, infectious diarrhea among children in developing countries.

PMID- 15480963
TI  - Prevention and treatment of malaria in young African children.
AB  - Malaria remains a major challenge to global public health, with morbidity and
      mortality rates being highest in African children infected with Plasmodium
      falciparum . All four species of human malaria may initially present as a
      nonspecific flu-like illness, whereas P. falciparum infection in nonimmune young
      children has a tendency to progress rapidly to life-threatening illness. These
      factors, together with the increasing emergence of multi-drug resistance, pose
      substantial challenges to current efforts to provide prompt and accurate
      diagnosis and effective treatment, particularly to the rural poor who are most
      affected by malaria. Acute episodes of severe malaria, repeated malaria
      infections leading to severe anemia, and infection during pregnancy which
      predisposes to low birth weight, a major risk factor for neonatal death, account
      for the majority of malaria-related deaths in young African children. Improved
      prevention and control strategies targeted at each of these clinical syndromes
      have been developed and are reviewed in this article. Coverage of protective
      measures of known safety and efficacy (insecticide-treated nets, Intermittent
      Preventive Treatment) remains alarmingly low in most high-burden areas. The
      growing global commitment to rapidly increase and sustain coverage among the most
      vulnerable populations, along with renewed investment in research to hasten the
      development of effective vaccines, antimalarial drugs, and insecticides, provides
      a unique opportunity to markedly reduce the burden of disease during the current
      decade.

PMID- 15480964
TI  - Pneumonia in children in the developing world: new challenges, new solutions.
AB  - Pneumonia has been a leading cause of death in both developed and developing
      countries as long as health indicators have been available. Yet the issues of
      concern for this syndrome are far from static. Improvements in access to health
      services have lowered infant mortality rates, benefiting children around the
      world and lowering the fraction of child deaths caused by pneumonia. However,
      progress has been interrupted repeatedly by the emergence of new pathogens.
      Landmark randomized controlled trials have now demonstrated the effectiveness of
      Haemophilus influenzae type b (Hib) and multivalent pneumococcal conjugate
      vaccines against childhood pneumonia, as well as meningitis and bacteremic
      disease. Momentum has gathered to tackle long-standing economic obstacles to
      expand access to new vaccines and programs for the poorest countries of the
      world. A pressing challenge for the control of pneumonia in developing countries
      is to identify better metrics for pneumonia. Surveillance tools are needed that
      will bridge studies of interventions, establish preventable disease burden, and
      serve as indicators for monitoring new programs.

PMID- 15480965
TI  - Prevention of pediatric human immunodeficiency virus.

PMID- 15480966
TI  - Emerging and re-emerging infectious diseases: review of general contributing
      factors and of West Nile virus.

PMID- 15480967
TI  - Stephen L. Cochi, MD, MPH: an outstanding leader in global eradication,
      elimination, and control of vaccine-preventable diseases.

PMID- 15480977
TI  - Evaluating discovery-based research: when biologic reasoning cannot work.

PMID- 15480978
TI  - Image of the month. Isolated dissection of the superior mesenteric artery.

PMID- 15480979
TI  - Suppression of Peutz-Jeghers polyposis by inhibition of cyclooxygenase-2.
AB  - BACKGROUND & AIMS: Peutz-Jeghers syndrome (PJS) is typically manifested as severe
      gastrointestinal polyposis. Polyps in PJS patients and in Lkb1(+/-) mice that
      model PJS polyposis are frequently characterized by elevated cyclooxygenase-2
      (COX-2). This study was designed to determine whether COX-2 inhibition would
      reduce tumor burden in Lkb1(+/-) mice or Peutz-Jeghers patients. METHODS: Genetic
      interactions between Cox-2 and Lkb1 in polyp formation were analyzed in mice with
      combined deficiencies in these genes. Pharmacologic inhibition of COX-2 was
      achieved by supplementing the diet of Lkb1(+/-) mice with 1500 ppm celecoxib
      between 3.5-10 and 6.5-10 months. In PJS patients, COX-2 was inhibited with a
      daily dose of 2 x 200 mg celecoxib for 6 months. RESULTS: Total polyp burden in
      Lkb1(+/-) mice was significantly reduced in a Cox-2(+/-) (53%) and in a Cox-2(-/
      ) (54%) background. Celecoxib treatment initiating before polyposis (3.5-10
      months) led to a dramatic reduction in tumor burden (86%) and was associated with
      decreased vascularity of the polyps. Late treatment (6.5-10 months) also led to a
      significant reduction in large polyps. In a pilot clinical study, a subset of PJS
      patients (2/6) responded favorably to celecoxib with reduced gastric polyposis.
      CONCLUSIONS: These data establish a role for COX-2 in promoting Peutz-Jeghers
      polyposis and suggest that COX-2 chemoprevention may prove beneficial in the
      treatment of PJS.

PMID- 15480981
TI  - Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients:
      results of a randomized double-blind trial.
AB  - BACKGROUND & AIMS: The gastric safety of cyclooxgenase-2 inhibitors and
      prophylactic antisecretory therapy in high-risk arthritis patients is unclear. We
      studied the ulcer incidence and factors predicting ulcer recurrence in a
      prospective, double-blinded trial. METHODS: We studied patients who presented
      with nonsteroidal anti-inflammatory drug-associated ulcer bleeding. After ulcer
      healing, patients who were negative for Helicobacter pylori were randomly
      assigned to celecoxib 200 mg twice a day plus omeprazole placebo once daily or
      diclofenac 75 mg twice daily plus omeprazole 20 mg once daily for 6 months.
      Patients underwent endoscopy if they developed recurrent bleeding. Those without
      recurrent events underwent endoscopy at their last follow-up visit. RESULTS: Two
      hundred eighty-seven patients were enrolled; 24 had recurrent gastrointestinal
      complications. Among 259 patients without events, 222 underwent endoscopy (116
      received celecoxib and 106 received diclofenac plus omeprazole). The probability
      of recurrent ulcers in 6 months was 18.7% in the celecoxib group and 25.6% in the
      diclofenac plus omeprazole group (difference, -6.7%; 95% CI: -17.8% to 3.9%) (P =
      0.21). Combining bleeding and endoscopic ulcers, 24.1% in the celecoxib group and
      32.3% in the diclofenac plus omeprazole group had recurrent ulcers in 6 months
      (difference, -8.2%; 95% CI: -19.5% to 2.9%) (P = 0.15). Treatment-induced
      significant dyspepsia (hazard ratio, 5.3; 95% CI: 2.6-10.8), age > or =75 (hazard
      ratio, 2.0; 95% CI: 1.1-3.5), and comorbidity (hazard ratio, 2.1; 95% CI: 1.2
      3.7) independently predicted ulcer recurrence. CONCLUSIONS: Among patients with
      previous ulcer bleeding, neither celecoxib nor diclofenac plus omeprazole
      adequately prevents ulcer recurrence. Treatment-induced significant dyspepsia is
      an indication for endoscopic evaluation.

PMID- 15480982
TI  - Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus
      patients.
AB  - BACKGROUND & AIMS: Endogenous hyperinsulinemia in the context of type 2 diabetes
      mellitus is potentially associated with an increased risk of colorectal cancer.
      We aimed to determine whether insulin therapy might increase the risk of
      colorectal cancer among type 2 diabetes mellitus patients. METHODS: We conducted
      a retrospective cohort study among all patients with a diagnosis of type 2
      diabetes mellitus in the General Practice Research Database from the United
      Kingdom. We excluded patients with <3 years of colorectal cancer-free database
      follow-up after the diabetes diagnosis as well as those insulin users who
      developed colorectal cancer after <1 year of insulin therapy. The remaining
      insulin users and the noninsulin-using type 2 diabetic patients were followed for
      the occurrence of colorectal cancer. Hazard ratios (HR) were determined in Cox
      proportional hazard analysis. A nested case-control study was conducted to
      perform multivariable analysis and to determine a duration-response effect.
      RESULTS: The incidence of colorectal cancer in insulin users (n = 3160) was 197
      per 100,000 person-years, compared with 124 per 100,000 person-years in type 2
      diabetes mellitus patients not receiving insulin (n = 21,758). The age- and sex
      adjusted HR of colorectal cancer associated with > or =1 year of insulin use was
      2.1 (95% CI: 1.2-3.4, P = 0.005). The positive association strengthened after
      adjusting for potential confounders. The multivariable odds ratio associated with
      each incremental year of insulin therapy was 1.21 (95% CI: 1.03-1.42, P = 0.02).
      CONCLUSIONS: Chronic insulin therapy significantly increases the risk of
      colorectal cancer among type 2 diabetes mellitus patients.

PMID- 15480983
TI  - Incidence of juvenile-onset Crohn's disease in Scotland: association with
      northern latitude and affluence.
AB  - BACKGROUND & AIMS: The incidence of Crohn's disease in Scottish children has
      increased steadily over 30 years. Many studies have investigated genetic
      influence or possible links with childhood events. We aimed to study
      sociodemographic and/or geographic distribution of juvenile=onset Crohn's disease
      in Scotland. METHODS: Using a previously established and validated database
      covering the entire Scottish population, 580 Scottish children (<16 years of age
      at symptom onset) with inflammatory bowel disease incident between 1981 and 1995
      were identified. Postcodes of incident cases were classed for geographic location
      and material deprivation. Incidence rates (/100,000/year) were sex standardized
      to the 1991 census population. The effects of sex, geographic location, time, and
      deprivation category were estimated from a multifactorial Poisson regression
      model. RESULTS: The incidence of juvenile-onset Crohn's disease was 2.3 (95% CI:
      2.0-2.5) for the time period 1981 to 1995 and was significantly higher in
      northern (3.1, 95% CI: 2.6-3.8) than in southern Scotland (2.1, 95% CI: 1.9-2.4,
      P < 0.001). The incidence of juvenile-onset ulcerative colitis did not show
      north/south variation ( P = 0.677). The relative risks of developing CD were
      significantly lower in postcode areas with deprivation categories 2-7 as compared
      with deprivation score 1 (most affluent, P = 0.033). This pattern was not seen
      for UC. CONCLUSIONS: There was an increased incidence of juvenile-onset Crohn's
      disease in northern compared with southern Scotland. Children from more affluent
      areas had a higher relative risk of developing Crohn's disease. Juvenile onset
      ulcerative colitis did not show north/south variation in incidence or association
      with affluence.

PMID- 15480984
TI  - Role of tension receptors in dyspeptic patients with hypersensitivity to gastric
      distention.
AB  - BACKGROUND & AIMS: Studies in health have shown that tension-sensitive
      mechanoreceptors mediate sensitivity to gastric distention. A role for these
      mechanoreceptors in perception or symptoms in hypersensitive functional dyspepsia
      (FD) has not been established. Tension-sensitive mechanoreceptors are activated
      during phasic contractions and inactivated during gastric relaxation. The aim of
      the present study was to investigate whether hypersensitive FD patients perceive
      spontaneous changes in fundic wall tension and whether fundus-relaxing drugs
      decrease sensitivity to gastric distention and meal-related symptoms. METHODS:
      Fifty patients were selected after a barostat study established gastric
      hypersensitivity. In 12 patients, an intragastric balloon was inflated with a
      fixed volume just below perception thresholds and patients were asked to indicate
      changes in perception on a keypad, and the relationship between perception and
      contractions was analyzed. In 20 patients, we studied the influence of the fundus
      relaxing drug sumatriptan on sensitivity to gastric distention. In, respectively,
      10 and 8 patients, we studied the influence of the fundus-relaxing drugs
      sumatriptan and clonidine on meal-related symptoms. RESULTS: The majority of
      patients had a statistically significant association between perception and
      phasic isovolumetric contractions. Pretreatment with sumatriptan increased both
      pressures and volumes needed to induce first perception and discomfort.
      Pretreatment with sumatriptan and clonidine both significantly decreased meal
      induced symptoms. CONCLUSIONS: Patients with hypersensitivity to gastric
      distention perceive isovolumetric phasic contractions of the proximal stomach.
      Fundus-relaxing drugs decrease sensitivity to gastric distention and decrease
      meal-induced symptoms in these patients. The findings are compatible with
      involvement of tension mechanoreceptors in symptom generation in hypersensitive
      FD.

PMID- 15480985
TI  - Endoscopic evaluation of patients with dyspepsia: results from the national
      endoscopic data repository.
AB  - BACKGROUND & AIMS: Endoscopy is commonly performed to evaluate symptoms of
      dyspepsia. The aim of this study was to characterize patients who receive
      endoscopy for dyspepsia and measure predictors of primary endoscopic outcomes,
      utilizing a large national endoscopic database. METHODS: The Clinical Outcomes
      Research Initiative (CORI) receives endoscopy reports from a network of 74 sites
      in the United States. Sixty-one percent of reports come from private practice
      settings. Patients with reflux dyspepsia and nonreflux dyspepsia were identified
      from January 2000 to June 2002. Patients with dysphagia and known Barrett's
      esophagus were excluded. Primary endoscopic outcomes included esophageal
      inflammation and stricture, gastric ulcer, duodenal ulcer, suspected Barrett's
      esophagus (> or =2 cm), and suspected esophageal and gastric malignancy. The
      presence or absence of alarm symptoms (vomiting, weight loss, and evidence of GI
      blood loss) was determined. Adjusted relative risk (RR) for predicting serious
      outcomes was calculated in a multivariate model. RESULTS: We received 117,497
      endoscopic reports, representing 99,558 unique patients. Dyspepsia, with and
      without reflux symptoms, accounted for 43% of upper endoscopies. Among dyspeptic
      patients, 36.5% were younger than 50 years of age without alarm symptoms.
      Esophageal or gastric malignancy in patients with dyspepsia was associated with
      increasing age, male sex, Asian race, Native American race, and symptoms of
      weight loss and vomiting. Suspected Barrett's esophagus (> or =2 cm) was
      associated with reflux symptoms, male sex, age, and white race. Ulcers were
      associated with evidence of bleeding, vomiting, male sex, black race, and
      Hispanic ethnicity. CONCLUSIONS: These practice-based data reveal important
      practice behaviors and outcomes.

PMID- 15480986
TI  - Genetic variants of the mannan-binding lectin are associated with immune
      reactivity to mannans in Crohn's disease.
AB  - BACKGROUND & AIMS: Some patients with Crohn's disease (CD) develop antibodies
      against mannan, a component of the yeast Saccharomyces cerevisiae cell wall.
      Mannan-binding lectin (MBL), a component of the innate immune system, can bind to
      S. cerevisiae . MBL concentration depends on genetic polymorphisms. The aim of
      this study was to evaluate whether low MBL contributes to anti-S. cerevisiae
      antibody (ASCA) production. METHODS: ASCA and MBL concentrations in sera from
      patients with CD (n = 74), ulcerative colitis (UC) (n = 22), and healthy controls
      (n = 32) were measured by an enzyme-linked immunosorbent assay (ELISA). Genetic
      MBL variants were determined from 58 CD patients, 18 UC patients, and 47 controls
      by DNA sequencing. Lymphocytes were tested for proliferative response after
      stimulation with mannan. RESULTS: ASCA were found in 47% of the patients with CD
      and in 0% of the controls. More ASCA-positive patients (52%) had low serum MBL
      concentrations compared with ASCA-negative patients (4%) (P < 0.0001). T-cell
      proliferation in response to mannan stimulation was observed in ASCA-positive
      patients and could be inhibited by the addition of MBL. These patients had
      significantly lower MBL serum concentrations than patients whose lymphocytes did
      not proliferate on mannan stimulation (P < 0.0001). Homozygous or compound
      heterozygous MBL mutations in the exon 1 and promoter occurred in 12 patients
      with cellular or humoral immune reactivity to mannan as compared with only 1
      nonreactive patient (P < 0.0001). CONCLUSIONS: A subgroup of CD patients is
      characterized by ASCA positivity, T-cell proliferation on mannan stimulation, and
      mutations in the MBL gene that result in MBL deficiency. Thus, we propose that
      enhanced mannan exposure stimulates specific immune responses in a subgroup of CD
      patients with genetically determined low MBL concentrations. This enhanced
      exposure contributes to the generation of ASCA.

PMID- 15480987
TI  - CFTR Cl- channel function in native human colon correlates with the genotype and
      phenotype in cystic fibrosis.
AB  - BACKGROUND & AIMS: Cystic fibrosis (CF) is caused by over 1000 mutations in the
      cystic fibrosis transmembrane conductance regulator (CFTR) gene and presents with
      a widely variable phenotype. Genotype-phenotype studies identified CFTR mutations
      that were associated with pancreatic sufficiency (PS). Residual Cl- channel
      function was shown for selected PS mutations in heterologous cells. However, the
      functional consequences of most CFTR mutations in native epithelia are not well
      established. METHODS: To elucidate the relationships between epithelial CFTR
      function, CFTR genotype, and patient phenotype, we measured cyclic adenosine
      monophosphate (cAMP)-mediated Cl- secretion in rectal biopsy specimens from 45 CF
      patients who had at least 1 non-DeltaF508 mutation carrying a wide spectrum of
      CFTR mutations. We compared CFTR genotypes and clinical manifestations of CF
      patients who expressed residual CFTR-mediated Cl- secretion with patients in whom
      Cl- secretion was absent. RESULTS: Residual anion secretion was detected in 40%
      of CF patients, and was associated with later disease onset (P < 0.0001), higher
      frequency of PS (P < 0.0001), and less severe lung disease (P < 0.05). Clinical
      outcomes correlated with the magnitude of residual CFTR activity, which was in
      the range of approximately 12%-54% of controls. CONCLUSIONS: Specific CFTR
      mutations confer residual CFTR function to rectal epithelia, which is related
      closely to a mild disease phenotype. Quantification of rectal CFTR-mediated Cl-
      secretion may be a sensitive test to predict the prognosis of CF disease and
      identify CF patients who would benefit from therapeutic strategies that would
      increase residual CFTR activity.

PMID- 15480988
TI  - TNFalpha suppresses human colonic circular smooth muscle cell contractility by
      SP1- and NF-kappaB-mediated induction of ICAM-1.
AB  - BACKGROUND & AIMS: Intercellular adhesion molecule 1 (ICAM-1) receptors are
      expressed at low levels on human colonic circular smooth muscle cells (HCCSMCs)
      and their expression is increased in patients with Crohn's disease. We
      investigated the roles of transcription factors Sp1 and nuclear factor kappa B
      (NF-kappaB) in the regulation of ICAM-1 expression on HCCSMCs and examined
      whether ICAM-1 expression mediates the suppression of contractility in response
      to TNFalpha. METHODS: Experiments were performed on primary cultures of HCCSMCs
      and fresh human colonic circular muscle strips. RESULTS: TNFalpha treatment of
      HCCSMCs induced rapid and prolonged accumulation of ICAM-1 messenger RNA (mRNA)
      and protein. NF-kappaB inhibition before, but not after, 1 hour of TNFalpha
      stimulation blocked the expression of ICAM-1. TNFalpha significantly enhanced
      Sp1/DNA binding. Sp1 bound to the 3' flanking region of a variant kappaB site in
      the -192/-172 region of ICAM-1 promoter. Mutation of this region abolished the
      response to TNFalpha. The treatment of HCCSMCs with Sp1 antisense
      oligonucleotides (ODNs) blocked the expression of ICAM-1, but sense ODNs had no
      effect. Protein kinase C zeta (PKCzeta) inhibition before or 3 hours after
      stimulation with TNFalpha also blocked the expression of ICAM-1. TNFalpha
      treatment of circular muscle strips pretreated with ICAM-1 sense ODNs or control
      medium significantly reduced their response to acetylcholine, whereas
      pretreatment with antisense ODNs blocked this effect. CONCLUSIONS: The expression
      of ICAM-1 on HCCSMCs in response to TNFalpha is regulated by transcription
      factors Sp1 and NF-kappaB binding independently to the -192/-172 region of the
      ICAM-1 promoter. The expression of ICAM-1 plays a critical role in the
      suppression of cell contractility in response to TNFalpha.

PMID- 15480989
TI  - Functional consequences of frizzled-7 receptor overexpression in human
      hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: The molecular pathogenesis of human hepatocellular carcinoma
      (HCC) is understood poorly. In some tumors, activation of the Wnt/beta-catenin
      pathway as a result of beta-catenin gene mutations has been found. However, in
      many other HCCs, activation of the Wnt/beta-catenin pathway has been shown in the
      absence of such mutations. METHODS: We previously have identified the upstream
      human Frizzled-7 receptor (FZD7) gene of this pathway. In the present study, a
      quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR)
      assay for FZD7 was developed and overexpression of FZD7 was detected in 90% of
      tumors, most of which were related to chronic hepatitis B virus infection. FZD7
      also was overexpressed in the 6 HCC cell lines tested and functional analysis
      showed that FZD7 messenger RNA (mRNA) levels correlated with enhanced cellular
      motility. RESULTS: Transfection of HCC cells with dominant-negative mutant
      constructs encoding a C-terminally truncated FZD7 protein decreased wild-type
      beta-catenin protein accumulation and reduced cell motility. More importantly, we
      observed beta-catenin accumulation in human HCC tumors containing the wild-type
      beta-catenin gene in the context of high-level FZD7 expression. CONCLUSIONS:
      These observations suggest that the Wnt/beta-catenin signal transduction pathway
      is involved much more commonly in the molecular pathogenesis of HCC than
      previously recognized because FZD7 overexpression occurred early in the disease
      process, stabilized wild-type beta-catenin levels, and contributed to enhanced
      tumor cell migration.

PMID- 15480990
TI  - Recombinant factor VIIa for upper gastrointestinal bleeding in patients with
      cirrhosis: a randomized, double-blind trial.
AB  - BACKGROUND & AIMS: Upper gastrointestinal bleeding (UGIB) is a severe and
      frequent complication of cirrhosis. Recombinant coagulation factor VIIa (rFVIIa)
      has been shown to correct the prolonged prothrombin time in patients with
      cirrhosis and UGIB. This trial aimed to determine efficacy and safety of rFVIIa
      in cirrhotic patients with variceal and nonvariceal UGIB. METHODS: A total of 245
      cirrhotic patients (Child-Pugh < 13; Child-Pugh A = 20%, B = 52%, C = 28%) with
      UGIB (variceal = 66%, nonvariceal = 29%, bleeding source unknown = 5%) were
      randomized equally to receive 8 doses of 100 microg/kg rFVIIa or placebo in
      addition to pharmacologic and endoscopic treatment. The primary end point was a
      composite including: (1) failure to control UGIB within 24 hours after first
      dose, or (2) failure to prevent rebleeding between 24 hours and day 5, or (3)
      death within 5 days. RESULTS: Baseline characteristics were similar between
      rFVIIa and placebo groups. rFVIIa showed no advantage over standard treatment in
      the whole trial population. Exploratory analyses, however, showed that rFVIIa
      significantly decreased the number of failures on the composite end point (P =
      0.03) and the 24-hour bleeding control end point (P = 0.01) in the subgroup of
      Child-Pugh B and C variceal bleeders. There were no significant differences
      between rFVIIa and placebo groups in mortality (5- or 42-day) or incidence of
      adverse events including thromboembolic events. CONCLUSIONS: Although no overall
      effect of rFVIIa was observed, exploratory analyses in Child-Pugh B and C
      cirrhotic patients indicated that administration of rFVIIa significantly
      decreased the proportion of patients who failed to control variceal bleeding.
      Dosing with rFVIIa appeared safe. Further studies are needed to verify these
      findings.

PMID- 15480991
TI  - Evolution of hepatitis B virus during primary infection in humans: transient
      generation of cytotoxic T-cell mutants.
AB  - BACKGROUND & AIMS: Acute hepatitis B is a highly dynamic human viral infection
      during which the hepatitis B virus can generate many genetic variants. METHODS:
      We analyzed the evolution of the hepatitis B virus genome in sequential serum
      samples from a unique cohort of patients with acute infection acquired from a
      single source. RESULTS: We showed that most mutations were nonsynonymous, that
      genetic diversity was greatest at the peak of viremia, and that patients who
      resolved their infection ("resolvers") showed a significantly higher level of
      diversity in the core, surface, and polymerase genes compared with those who
      progressed to chronic infection. Overall, the core gene showed the greatest
      genetic diversity. In resolvers who possessed an HLA-A*0201 haplotype, the
      emergence of mutants in the immunodominant HLA-A*0201-restricted core 18-27
      epitope was observed. Functional studies showed that these mutants were less able
      to stimulate interferon-gamma release from core 18-27 specific CD8 + T-cell
      lines. However, they appeared only as a transient low-abundance species and were
      rapidly displaced by wild-type sequences before resolution of infection, and
      their overall significance is uncertain. CONCLUSIONS: Overall, genetic evolution
      of the hepatitis B virus differs at early time points between patients who
      experience acute resolving hepatitis B and those who progress to chronicity.
      These observations suggest that the rapid development of broadly reactive host
      immune responses leads to clearance of hepatitis B virus, even in the presence of
      possible CD8+ T-cell immune escape variants.

PMID- 15480992
TI  - Apobec-1 protects intestine from radiation injury through posttranscriptional
      regulation of cyclooxygenase-2 expression.
AB  - BACKGROUND & AIMS: This study aimed to determine the role of the RNA binding
      protein apobec-1 in radioprotection of the intestine. METHODS: Apobec-1-deleted
      mice (APOBEC-1(-/-)) and wild-type controls were treated with 12 Gy of whole-body
      gamma-irradiation in a cesium irradiator. The number of surviving intestinal
      crypts was assessed 3.5 days after irradiation by using a clonogenic assay.
      Cyclooxygenase-2 messenger RNA and protein expression were determined by real
      time polymerase chain reaction and Western blot, respectively. RNA stability was
      studied by examining the turnover of a chimeric transcript containing the
      cyclooxygenase-2 3' untranslated region cloned downstream of luciferase
      complementary DNA. Apobec-1 binding to the cyclooxygenase-2 3' untranslated
      region was studied by electrophoretic mobility shift and UV crosslinking assays.
      RESULTS: After gamma-irradiation, the survival of intestinal stem cells decreased
      significantly in APOBEC-1(-/-) mice. In wild-type mice treated with
      lipopolysaccharide before gamma-irradiation, intestinal stem cells were protected
      by marked increases in prostaglandin E 2 mediated by cyclooxygenase-2. No such
      effect was observed in the APOBEC-1(-/-) mice. The mechanism of this
      radioprotective effect involves the binding of apobec-1 to AU-rich sequences in
      the first 60 nucleotides of the 3' untranslated region of cyclooxygenase-2. Upon
      binding to the AU-rich sequences, apobec-1 stabilizes cyclooxygenase-2 messenger
      RNA. This stabilization process does not seem to be mediated by p38 mitogen
      activated protein kinase pathways. CONCLUSIONS: Lipopolysaccharide increases
      intestinal stem cell survival through apobec-1-mediated regulation of
      cyclooxygenase-2 messenger RNA stability.

PMID- 15480993
TI  - The Akt and MAPK signal-transduction pathways regulate growth factor actions in
      isolated gastric parietal cells.
AB  - BACKGROUND & AIMS: Incubation of purified (>95%) canine parietal cells in primary
      culture with epidermal growth factor for 7-16 hours stimulates H(+)K(+)-adenosine
      triphosphatase gene expression. In this study, we examined the effect of
      prolonged stimulation (72 hours) of the parietal cells with epidermal growth
      factor. METHODS: H(+)K(+)-adenosine triphosphatase protein and gene expression
      were assessed by immunohistochemistry and Northern blots. Mitogen-activated
      protein kinase and Akt activation were quantitated by kinase assays and Western
      blots with specific antiphospho antibodies. Akt overexpression was achieved by
      adenovirus-mediated gene transfer of a constitutively active Akt gene. RESULTS:
      Epidermal growth factor changed the morphology of the cultured cells, which
      acquired the appearance of fusiform cells, and it inhibited H(+)K(+)-adenosine
      triphosphatase gene expression. Staining of the cells both with anti-H(+)K(+)
      adenosine triphosphatase antibodies and with Texas Red-labeled Dolichos biflorus
      lectin confirmed that the fusiform cells expressed markers of parietal cell
      differentiation. Epidermal growth factor stimulated mitogen-activated protein
      kinase with 2 peaks of activation, observed after 5 minutes and 72 hours, whereas
      it activated Akt after 5 minutes but not 72 hours of incubation. Overexpression
      of Akt blocked both epidermal growth factor-induced morphological transformation
      and inhibition of H + K + -adenosine triphosphatase gene expression. Identical
      results were observed in the presence of the mitogen-activated protein kinase
      inhibitor PD98059. CONCLUSIONS: Activation of the Akt signal-transduction pathway
      seems to be a crucial event for the induction of parietal cell maturation and
      differentiation.

PMID- 15480994
TI  - Cystic fibrosis gene mutation reduces epithelial cell acidification and injury in
      acid-perfused mouse duodenum.
AB  - BACKGROUND & AIMS: Dysfunction of the cystic fibrosis transmembrane regulator
      (CFTR) is associated with diminished duodenal HCO3- secretion, despite a reported
      lack of clinical duodenal ulceration in affected subjects. We hypothesized that
      duodenal epithelial cells expressing a mutant CFTR have enhanced resistance to
      acid-induced injury. To test this hypothesis, we measured duodenal epithelial
      cell intracellular pH (pHi), injury, and acid back-diffusion in response to a
      luminal acid challenge in transgenic mice. METHODS: A murine colony was
      established for the CFTR DeltaF508 (DeltaF) mutation. Epithelial cell pH i was
      measured by microscopy with a trapped, fluorescent pH-sensitive dye in living
      C57BL/6 and DeltaF/DeltaF, +/DeltaF, and +/+ mice. In vivo confocal microscopy
      confirmed the localization of the dye in the cytoplasm of the epithelial cells.
      Epithelial injury was measured fluorometrically using propidium iodide. Duodenal
      epithelial bicarbonate secretion and proton permeability were measured by back
      titration. Bicarbonate secretion and acid back-diffusion were measured in a
      perfused duodenal loop. RESULTS: Basal and post-acid exposure bicarbonate
      secretion were reduced in DeltaF/DeltaF mice, although acid back-diffusion was
      similar to controls. Epithelial pHi of CFTR DeltaF/DeltaF mice during luminal
      acid exposure was significantly higher than pHi in +/DeltaF, +/+, or C57BL/6
      mice. Acid-related epithelial injury was markedly less in DeltaF/DeltaF mice in
      comparison with the other groups. CONCLUSIONS: Increased cellular buffering power
      of the epithelial cells of DeltaF/DeltaF mice likely protects against
      acidification and injury during acid exposure. We speculate that this protective
      mechanism partially underlies the perceived relative lack of peptic ulceration in
      patients affected by cystic fibrosis.

PMID- 15480995
TI  - Regulation of hepatic stellate cell activation and growth by transcription factor
      myocyte enhancer factor 2.
AB  - BACKGROUND & AIMS: Hepatic stellate cells (HSCs) undergo activation during the
      development of liver fibrosis. Transcriptional regulation plays a key role in
      this process. We studied the role of transcription factor myocyte enhancer factor
      2 (MEF2) during HSC activation. METHODS: Culture of HSCs isolated from rat liver
      on plastic dishes and HSC-T6 on a basement membrane-like matrix were used as
      models of HSC activation and deactivation, respectively. The expression and
      activity of MEF2 were correlated with HSC activation. The roles of MEF2 during
      HSC activation were assessed in vitro and in vivo by animal models of fibrosis.
      RESULTS: Early induction of MEF2 messenger RNA and protein accompanied culture
      induced HSC activation. This was associated with enhanced MEF2 DNA binding and
      transactivation activity. p38 mitogen-activated protein kinase but not
      extracellular signal-regulated kinase pathway was required for increased MEF2
      activity during HSC activation. Increased MEF2 protein also correlated with
      fibrosis in vivo. Reversal of HSC activation was paralleled by a marked decrease
      in MEF2 protein and activity. Functionally, enhancing MEF2 significantly
      increased the expression of alpha-smooth muscle actin (alpha-SMA), activated
      collagen I promoter activity, and stimulated HSC proliferation. MEF2 interference
      RNA significantly inhibited expression of alpha-SMA, collagen alpha1(I), and
      proliferating cell nuclear antigen. CONCLUSIONS: The studies provide the first
      evidence for the presence of MEF2 in the liver and show that MEF2 regulates
      multiple aspects of HSC activation. These studies show a novel role of MEF2 as a
      key nuclear mediator that may participate in the pathologic process of liver
      fibrogenesis in vivo.

PMID- 15480996
TI  - Hepatocyte-specific disruption of Bcl-xL leads to continuous hepatocyte apoptosis
      and liver fibrotic responses.
AB  - BACKGROUND & AIMS: Recent research has suggested that apoptosis could be involved
      in the development of fibrosis, although it is generally considered to be a
      mechanism of cell removal without consequences to the tissue. Bcl-xL , an
      antiapoptotic member of the Bcl-2 family, is expressed in hepatocytes and up
      modulated during various pathologic conditions. The aim of this study was to
      explore the function of Bcl-xL in hepatocytes using the Cre-loxP system and to
      analyze the consequences of long-term apoptosis in hepatocytes. METHODS:
      Hepatocytes isolated from mice homozygous for a floxed bcl-x allele (bcl-x fl/fl)
      were infected with recombinant adenovirus expressing the Cre recombinase gene
      (AdexCre). Bcl-x fl/fl mice were crossed with Alb-Cre transgenic mice, which
      express Cre under regulation of the albumin gene promoter to generate hepatocyte
      specific Bcl-xL-deficient mice. RESULTS: On AdexCre infection, primary cultured
      bcl-x fl/fl hepatocytes reduced their expression of Bcl-xL and rapidly underwent
      apoptosis associated with mitochondrial damage. In vivo hepatocyte-specific
      disruption of Bcl-xL resulted in spontaneous apoptosis of hepatocytes for more
      than 6 months. The Bcl-xL -deficient mice showed liver fibrosis with advanced age
      that was preceded by an increase in hepatic transforming growth factor beta
      production. In vitro, macrophages and hepatocytes produced transforming growth
      factor beta on exposure to apoptotic hepatocytes. CONCLUSIONS: The present study
      identified Bcl-xL as a critical apoptosis antagonist in hepatocytes. Furthermore,
      it offers proof that persistent apoptosis of parenchymal cells is sufficient to
      induce fibrotic responses and suggests a mechanistic link between apoptosis and
      fibrosis.

PMID- 15480997
TI  - Nerve growth factor modulates the proliferative capacity of the intrahepatic
      biliary epithelium in experimental cholestasis.
AB  - BACKGROUND & AIMS: We evaluated the expression of neurotrophins in rat
      cholangiocytes and the role and mechanisms by which nerve growth factor (NGF)
      modulates cholangiocyte proliferation. METHODS: The expression of neurotrophins
      and their receptors was investigated by immunohistochemistry in liver sections
      and reverse-transcription polymerase chain reaction and immunoblots in isolated
      cholangiocytes. In vitro, the effect of NGF on cholangiocyte proliferation and
      signal transduction was investigated by immunoblotting for proliferating cell
      nuclear antigen, phosphorylated AKT (p-AKT), phosphorylated extracellular signal
      regulated kinase 1/2 (p-ERK1/2), phosphorylated c-jun-N-terminal kinase, and
      phosphorylated p38. In vivo, rats that had undergone bile duct ligation (BDL)
      were treated with an anti-NGF antibody to immunoneutralize NGF and bile duct
      mass, proliferation, apoptosis, and inflammation were investigated by
      immunohistochemistry. RESULTS: NGF and its TrkA receptor were expressed by normal
      rat cholangiocytes and up-regulated following BDL. Cholangiocytes secrete NGF,
      and secretion is increased in proliferating BDL cholangiocytes. In vitro, NGF
      stimulated cholangiocyte proliferation, which was associated with enhanced p-AKT
      and p-ERK1/2 expression. NGF proliferation in vitro was partially blocked by the
      MEK inhibitor (UO126) and completely ablated by the phosphatidylinositol 3-kinase
      inhibitor (wortmannin). In vitro, NGF and estrogens have an additive effect on
      cholangiocyte proliferation by acting on phosphorylated TrkA and p-ERK1/2. In
      vivo, immunoneutralization of NGF decreased bile duct mass in BDL rats, which was
      associated with depressed proliferation and enhanced apoptosis and with increased
      portal inflammation. CONCLUSIONS: Cholangiocytes secrete NGF and express NGF
      receptors. NGF induces cholangiocyte proliferation by activating the ERK and,
      predominantly, the phosphatidylinositol 3-kinase pathway and exerts an additive
      effect in combination with estrogens on proliferation.

PMID- 15480998
TI  - Hepatic response to right ventricular pressure overload.
AB  - BACKGROUND & AIMS: Modifying the afferent blood supply to the liver does not
      change the zonal expression pattern of hepatic enzymes in the rat. METHODS: We
      used pulmonary trunk banding (PTB) to study the effect of an efferent hindrance
      of blood flow on hepatic architecture and zonation of gene expression. RESULTS:
      Most PTB rats developed right ventricular hypertrophy and congestive heart
      failure. The hepatic response to PTB developed concomitantly with the decline in
      heart function. Enzyme expression in the periportal region was not affected, but
      the pericentral rim of hepatocytes expressing glutamine synthetase, ornithine
      aminotransferase, and NADPH cytochrome P-450 reductase (CYPred) first declined in
      diameter, then became discontinuous, and finally disappeared. Meanwhile,
      ornithine aminotransferase and especially CYPred, became re-expressed in the
      periportal zone. These changes occurred without appreciable cell death or
      fibrotic changes; the expression of fibronectin and alpha-smooth muscle actin
      increased perisinusoidally, but that of collagen did not. Electron microscopic
      analysis revealed normal fenestration of the sinusoidal endothelial cells without
      detectable deposition of basement membrane material, but both the width of the
      space of Disse and the length and number of hepatic microvilli were significantly
      reduced, implying a decreased flow of fluid in the space of Disse. CONCLUSIONS:
      The reprogramming of gene expression in livers with a postsinusoidal hindrance of
      blood flow results from declining access of the hepatocytes to intrasinusoidal
      signal-transduction molecules and suggest that the impaired biotransformation
      that accompanies right ventricular failure is caused by a central-to-portal shift
      in expression of the corresponding enzymes.

PMID- 15480999
TI  - Gene therapy for human alpha1-antitrypsin deficiency in an animal model using
      SV40-derived vectors.
AB  - BACKGROUND & AIMS: In most genetic diseases, the goal of gene therapy is to
      deliver a particular transgene; however, sometimes a deleterious gene product
      must be eliminated. Because of the promise of recombinant simian virus 40 (rSV40)
      vectors, we tested their ability to deliver a transgene and to target a
      transcript for destruction by direct administration of the vectors to the liver
      of an animal model for human alpha1-antitrypsin (alpha1-AT) deficiency. METHODS:
      Therapy of human alpha1-AT deficiency requires stable transduction of resting
      hepatocytes, both to deliver wild-type alpha1-AT and to inhibit production of
      mutant alpha1-AT. Transgenic mice carrying the mutant human alpha1-AT PiZ allele
      were treated through an indwelling portal vein catheter with a simian virus 40
      (SV40)-derived vector carrying a ribozyme designed to target the human
      transcript. RESULTS: Treated transgenic mice showed marked decreases of human
      alpha1-AT messenger RNA and the protein in the liver, and serum levels of human
      alpha1-AT were decreased to 50% +/- 5% of pretreatment values 3-16 weeks after
      transduction. Moreover, when normal mice were treated with an SV40-derived vector
      containing a modified human alpha1-AT complementary DNA engineered to be
      resistant to cleavage by the alpha1-AT ribozyme, they expressed human alpha1-AT
      messenger RNA and protein in their livers and serum levels of human alpha1-AT
      remained >1 microg/mL for 1 year. CONCLUSIONS: These results represent the
      initial steps toward a novel approach to the gene therapy of alpha1-AT
      deficiency.

PMID- 15481000
TI  - Low-grade dysplasia in Barrett's esophagus.

PMID- 15481001
TI  - Pathophysiology and treatment of functional dyspepsia.

PMID- 15481002
TI  - COX-2-specific inhibitor or proton pump inhibitor plus traditional NSAID: is
      either approach sufficient for patients at highest risk of NSAID-induced ulcers?

PMID- 15481003
TI  - Inflammation activates Apobec-1 and stabilizes multiple anti-apoptotic mRNAs.

PMID- 15481004
TI  - From quiescence to activation: Gene regulation in hepatic stellate cells.

PMID- 15481005
TI  - Sperm, sex, and 6-MP: the perception on conception.

PMID- 15481006
TI  - Cutlery for the endoscopists--know your knife!

PMID- 15481007
TI  - Intestinal malignancy and campylobacter jejuni.

PMID- 15481009
TI  - Surgical versus endoscopic palliation of malignant gastric outlet obstruction:
      big incision, little incision, or no incision?

PMID- 15481010
TI  - Surveillance plus chemoprevention in cirrhotic patients with HCV: a better
      outlook for HCC?

PMID- 15481017
TI  - Discussion on independent influences of body mass and gastric volumes on
      satiation in humans.

PMID- 15481019
TI  - Computed tomography and magnetic resonance imaging in the assessment of acute
      pancreatitis.

PMID- 15481021
TI  - Statin-induced hepatotoxicity.

PMID- 15481022
TI  - Hepatitis C and diabetes mellitus: what is the metabolic pathway?

PMID- 15481023
TI  - Discussion on prophylactic antibiotic use in severe acute pancreatitis: hemlock,
      help, or hype?

PMID- 15481026
TI  - Self-assembly of human serum albumin (HSA) and L-alpha-dimyristoylphosphatidic
      acid (DMPA) microcapsules for controlled drug release.
AB  - Human serum albumin (HSA) and L-alpha-dimyristoylphosphatidic acid (DMPA) were
      applied as a pair to encapsulate ibuprofen microcrystals by means of a technique
      based on the layer-by-layer (LbL) assembly of oppositely charged species, for the
      purpose of controlling drug release. The successful adsorption of HSA and DMPA
      multilayers onto ibuprofen crystals was confirmed by optical microscopy. The drug
      release process, in a solution of pH 7.4, was monitored by optical microscopy and
      UV spectroscopy. The results revealed that the rate of release of ibuprofen from
      HSA/DMPA microcapsules decreased as the capsule wall thickness and drug crystal
      size increased, indicating that the permeability of the microcapsules can be
      controlled by simply varying the number of HSA/DMPA deposition cycles.

PMID- 15481027
TI  - Some novel binuclear group 13 metal tin hydrides formed in Ar matrices following
      the codeposition of the metal vapor with SnH4.
AB  - IR measurements show that co-condensation of Al or Ga atoms (M) with SnH4 in a
      solid Ar matrix at about 12 K results mainly in the spontaneous insertion of the
      metal into an Sn-H bond to form the M(II) hydride HMSnH3. Simultaneously the Ga2
      dimer also reacts with SnH4, possibly to form a nido-type cluster Ga2(mu-H)4Sn,
      with a metal-deficient cubane-like structure. All of these products are
      photolabile. Irradiation with visible light causes HMSnH3 to tautomerize to the
      novel dihydrido-bridged species H3M(mu-H)2Sn, which decomposes in turn under
      broad-band UV-visible light (lambda=200-800 nm); some H3Al(mu-H)2Sn is formed
      even on deposition. The data collected from experiments with SnH4 and SnD4 and
      different reagent concentrations, together with the results of quantum chemical
      calculations, are used to interpret the results and elucidate the structures and
      bonding of the new species.

PMID- 15481028
TI  - Abnormalities in the NF-kappaB family and related proteins in endometrial
      carcinoma.
AB  - The NF-kappaB family of transcription factors regulates a wide variety of
      cellular processes including cell growth, differentiation, and apoptosis. A
      tissue microarray was constructed from paraffin wax-embedded blocks from 95
      endometrial carcinomas (EC), previously studied for microsatellite instability,
      as well as for alterations in PTEN, k-RAS and beta-catenin. Immunohistochemical
      evaluation included members of the NF-kappaB (p50, p65, p52, c-Rel, Rel-B) and
      the IkappaB (IkappaBalpha, IkappaBbeta, IkappaBepsilon, Bcl-3) families, as well
      as putative targets of NF-kappaB such as Flip, Bcl-xL, Cyclin D1, and oestrogen
      and progesterone receptors. Results were correlated with the clinical and
      pathological data. Nuclear immunostaining for members of the NF-kappaB family was
      frequent in EC (p50, 20%; p65, 16.5-21.9%; p52, 9.3%; c-Rel, 48.9%; Rel-B,
      15.7%); and it correlated with negativity for members of the IkappaB family in
      some cases. There was a statistically significant association between
      immunoreaction for p50 and p65 (p = 0.006), suggesting activation of the so
      called 'classic form' of NF-kappaB, similar to that described in breast cancer.
      Bcl-3 nuclear immunostaining was detected in 60.7% of cases. The vast majority of
      p52-positive tumours showed Bcl-3 nuclear immunoreaction (p = 0.038).
      Immunostaining for putative targets of NF-kappaB was as follows: Bcl-xL, 76.2% (p
      = 0.001); Flip 43.0%; Cyclin D1, 64.79%. p65 immunostaining correlated with
      increased immunoreaction for steroid hormone receptors. No correlation was found
      between NF-kappaB nuclear pattern and the presence of microsatellite instability,
      or alterations in PTEN, k-RAS, or beta-catenin. These results suggest that the NF
      kappaB and IkappaB families of genes may be important in endometrial
      carcinogenesis, by controlling apoptosis and cell proliferation.

PMID- 15481029
TI  - Synthesis and degradation of nucleobases and nucleic acids by formamide in the
      presence of montmorillonites.
AB  - We describe the role of formamide, a product of the hydrolysis of hydrogen
      cyanide, as precursor of several components of nucleic acids under prebiotic
      conditions. When formamide is heated in the presence of montmorillonites, the
      efficient one-pot synthesis of purine, adenine, cytosine, and uracil is obtained.
      Along with these nucleobases, several components of the inosine pathway are
      obtained: 5-aminoimidazole-4-carboxamide, 5-formamidoimidazole-4-carboxamide and
      hypoxanthine. This almost complete catalogue of nucleic acid precursors is
      accompanied by N(9)-formylpurine, which, containing a masked glycosidic bond in
      its formyl moiety, is a plausible precursor of purine acyclonucleosides. In
      addition, montmorillonites differentially affect the rate of degradation of
      nucleobases when embedded in 2'-deoxyoligonucleotides; namely, montmorillonites
      protect adenine and guanine from the degradative action of formamide, while
      thymine degradation is enhanced. The oligonucleotide backbone reactivity to
      formamide is also affected; this shows that the interaction with montmorillonites
      modifies the rate of abstraction of the Halpha and Hbeta protons on the sugar
      moieties.

PMID- 15481030
TI  - NMR backbone assignment of a protein kinase catalytic domain by a combination of
      several approaches: application to the catalytic subunit of cAMP-dependent
      protein kinase.
AB  - Protein phosphorylation is one of the most important mechanisms used for
      intracellular regulation in eukaryotic cells. Currently, one of the best
      characterized protein kinases is the catalytic subunit of cAMP-dependent protein
      kinase or protein kinase A (PKA). PKA has the typical bilobular structure of
      kinases, with the active site consisting of a cleft between the two structural
      lobes. For full kinase activity, the catalytic subunit has to be phosphorylated.
      The catalytic subunit of PKA has two main phosphorylation sites: Thr197 and
      Ser338. Binding of ATP or inhibitors to the ATP site induces large structural
      changes. Here we describe the partial backbone assignment of the PKA catalytic
      domain by NMR spectroscopy, which represents the first NMR assignment of any
      protein kinase catalytic domain. Backbone resonance assignment for the 42 kDa
      protein was accomplished by an approach employing 1) triply ((2)H,(13)C,(15)N)
      labeled protein and classical NMR assignment experiments, 2) back-calculation of
      chemical shifts from known X-ray structures, 3) use of paramagnetic adenosine
      derivatives as spin-labels, and 4) selective amino acid labeling. Interpretation
      of chemical-shift perturbations allowed mapping of the interaction surface with
      the protein kinase inhibitor H7. Furthermore, structural conformational changes
      were observed by comparison of backbone amide shifts obtained by 2D (1)H,(15)N
      TROSY of an inactive Thr197Ala mutant with the wild-type enzyme.

PMID- 15481031
TI  - Imaging the selective binding of synapsin to anionic membrane domains.
AB  - Synapsins are membrane-associated proteins that cover the surface of synaptic
      vesicles and are responsible for maintaining a pool of neurotransmitter-loaded
      vesicles for use during neuronal activity. We have used atomic force microscopy
      (AFM) to study the interaction of synapsin I with negatively charged lipid
      domains in phase-separated supported lipid bilayers prepared from mixtures of
      phosphatidylcholines (PCs) and phosphatidylserines (PSs). The results indicate a
      mixture of electrostatic binding to anionic PS-rich domains as well as some
      nonspecific binding to the PC phase. Interestingly, both protein binding and
      scanning with synapsin-coated AFM tips can be used to visualize charged lipid
      domains that cannot be detected by topography alone.

PMID- 15481032
TI  - Identification and biosynthesis of an aggregation pheromone of the storage mite
      Chortoglyphus arcuatus.
AB  - In an effort to identify new pheromones from mites, the headspace of undisturbed
      colonies of the storage mite Chortoglyphus arcuatus was analyzed by GC-MS by use
      of a closed-loop stripping apparatus (CLSA) or solid-phase microextraction
      (SPME). The major compound emitted from the mites is (4R,6R,8R)-4,6,8
      trimethyldecan-2-one (4R,6R,8R-8). The structure was elucidated by analysis of
      the mass spectrum, synthesis of authentic samples, and gas chromatography on a
      chiral phase. Bioassays show that this compound, for which we propose the trivial
      name chortolure, is an aggregation pheromone for both sexes of this species.
      Several related compounds are released in smaller amounts by the mites. The alarm
      pheromones of these mites, neral and geranial, can only be found in total
      extracts of the mites, in which 8 occurs only in minute amounts. The method of
      sampling is therefore crucial for pheromone identification. Feeding experiments
      with deuterated propionate showed that chortolure is a polyketide, formed by
      successive addition of four propionate units to an acetate starter.

PMID- 15481033
TI  - Three patients with 9p deletions including DMRT1 and DMRT2: a girl with XY
      complement, bilateral ovotestes, and extreme growth retardation, and two XX
      females with normal pubertal development.
AB  - It is well documented that distal 9p monosomy can be associated with XY sex
      reversal. Recently, the possibility of DMRT1 and/or DMRT2 (the genes for
      doublesex and mab-3 related transcription factor 1 and 2) being the sex
      determining genes(s) at 9p has been raised. DMRT1 and DMRT2 map near the 9p
      telomere, distal of marker D9S1779. We describe here three unrelated females with
      distal 9p monosomy, one with XY complement and two with XX complements. In each
      individual, fluorescent in situ hybridization predicted the loss of the DMRT
      genes. Patient 1, an XY individual with monosomy 9pter --> p24.1 approximately
      24.2 and trisomy 7q32 --> qter had normal female external genitalia, a blind
      ending vagina, no uterus, a Fallopian tube on the right, and bilateral ovotestes
      with primitive ovarian tissue. She also had extreme growth retardation. Around 80
      cases of distal 9p monosomy have been reported previously, but there has been no
      report of ovotestes or gonads comprising ovarian tissue in a XY patient with 9p
      deletion. Findings in Patient 1 suggest that the phenotypic spectrum of the
      heterozygous DMRT deletion may include true hermaphroditism. Patients 2 and 3
      were 12- and 14-year-old females with XX complements, normal external genitalia,
      and normal pubertal development. Patient 2 had pure monosomy 9pter --> p23 and
      Patient 3 had monosomy 9pter --> p22.3 approximately 23 combined with trisomy
      3pter --> p23 approximately 24. To date, detailed reports on the gonadal status
      of XX 9p-females have been limited to prepubertal girls. Patients 2 and 3 are the
      first females reported to have distal 9p monosomy and a normal puberty.

PMID- 15481034
TI  - Cerebellar hypoplasia, zonular cataract, and peripheral neuropathy in trisomy 17
      mosaicism.
AB  - Trisomy 17 mosaicism in liveborns is an extremely rare chromosomal abnormality,
      with only three cases reported in the literature. Here we describe a 7-year-old
      boy with trisomy 17 mosaicism. The chromosome abnormality was detected by
      amniocentesis and was confirmed postnatally in cultured skin fibroblasts. The
      main clinical features were mental retardation and growth reduction, peripheral
      motor and sensory neuropathy, hypoplastic cerebellar vermis, zonular cataract,
      and body asymmetry. In our patient, and in the three earlier described cases, the
      additional chromosome 17 was detected in skin fibroblasts, not in peripheral
      lymphocytes. Molecular investigations excluded uniparental disomy of chromosome
      17 in our patient. The extra chromosome 17 probably originated from a postzygotic
      mitotic nondisjunction of the maternal chromosome 17. In most cases of trisomy 17
      mosaicism detected in amniocytes the chromosome abnormality seems to be confined
      to extra-embryonic tissues and clinically normal children are born. If, however,
      there are also ultrasound abnormalities, the possibility of fetal trisomy 17
      mosaicism should certainly be considered. If postnatal karyotyping is limited to
      blood the diagnosis of trisomy 17 mosaicism could easily be missed. Therefore, we
      recommend chromosome analysis to be based on cultured skin fibroblasts in all
      cases where mental retardation is accompanied by postnatal growth retardation,
      body asymmetry, peripheral neuropathy, and cerebellar hypoplasia or zonular
      cataract.

PMID- 15481035
TI  - Effect of low-power pulsed laser on peripheral nerve regeneration in rats.
AB  - The purpose of this study was to determine whether low-power pulsed laser
      irradiation could affect the regeneration of a 10-mm gap of rat sciatic nerve
      created between the proximal and distal nerve stumps, which were sutured into
      silicone rubber tubes. After 8 weeks of recovery, pulsed laser-irradiated groups
      at frequencies of 5 kHz and 20 kHz both had significantly lower success
      percentages of regeneration (50% and 44%, respectively) compared to sham
      irradiated controls (100%). In addition, qualitative and quantitative histology
      of the regenerated nerves revealed a less mature ultrastructural organization
      with a smaller cross-sectional area and a lower number of myelinated axons in
      both pulsed laser-irradiated groups than in controls. These results suggest that
      pulsed laser irradiation could elicit suppressing effects on regenerating nerves.

PMID- 15481036
TI  - Is SHORT syndrome another phenotypic variation of PITX2?
AB  - Even though responsible genetic loci and mode of inheritance for the Rieger
      syndrome have been well established, the mode of inheritance and the genetic
      basis for SHORT syndrome are still uncertain. The purpose of this paper is to
      document a familial translocation of t(1;4)(q31.2;q25), in a mother and her son
      manifesting Rieger syndrome with polycystic ovaries and SHORT syndrome,
      respectively. It is suggested that these two syndromes may be different
      expressions of the same gene, PITX2, localized at 4q25. Our patient is the second
      with the association of Rieger syndrome and polycystic ovaries, and thus this may
      not be coincidental, moreover insulin resistance-related phenotypes, such as
      lipodystrophy and polycystic ovaries, can be major component of syndromes with
      Rieger eye malformation.

PMID- 15481037
TI  - Simplified technique for heterotopic vascularized cervical heart transplantation
      in mice.
AB  - Technical problems have limited the widespread use of mouse vascularized heart
      transplantation as a medical research tool. In this report, we describe a
      simplified method for performing heterotopic cervical transplantation by the cuff
      technique. The right pulmonary artery of the donor heart is equipped with a 22
      gauge cuff. The aortic arch is isolated and transected at the level of the
      brachiocephalic artery. After proximally ligating the inferior vena cava with 9-0
      silk, the residual blood vessels and lungs are ligated proximally and then
      carefully transected. The carotid artery is then everted over the Teflon cuff.
      Using this modified procedure, the operation from harvesting the donor heart to
      skin closure of the recipient mouse can be completed within 35 min. This
      simplified method for mouse heart transplantation was shown to have a high
      success rate, and is practical for use in transplantation immunology research.

PMID- 15481038
TI  - Biochemistry of carpal tunnel syndrome.
AB  - Although carpal tunnel syndrome (CTS) occurs due to intrinsic or extrinsic
      causes, the idiopathic group outnumbers the rest by far. Compression of the
      median nerve may be due to mechanical or ischemic causation. The cause of
      idiopathic CTS is thought to be intermittent compression of the median nerve in
      predisposed people, especially working females, producing ischemia of the nerve.
      Reperfusion injury may occur during periods of recovery. Intermittent perfusion
      of the cellular tissue following ischemia releases free oxygen radicals. With
      continued oxidative stress, the normal antioxidant system is overwhelmed and
      cellular injury ensues, affecting both nerve and synovial cells. This is
      confirmed by changes seen locally in nerve and synovial tissue both serologically
      and histologically. These changes are reverted or checked by the use of
      antioxidants in vitro. Simulated compression of the nerve in laboratory animals
      also confirms these findings, further corroborating the pathophysiology and
      suggesting means of preventing idiopathic CTS.

PMID- 15481039
TI  - Free functional rectus femoris muscle transfer for restoration of extension of
      the foot after lower leg compartment syndrome.
AB  - In severely injured lower extremities with loss of the anterior compartment, the
      free functional rectus femoris musculocutaneous flap was used to restore
      extension of the foot and in soft-tissue reconstruction. From June 2000-July
      2002, 3 patients were treated with this technique. Mean follow-up of the 3
      patients was 27 months. Electromyography and the Stanmore system (recording pain,
      need for orthosis, ability to wear normal shoes, activity level, muscle power,
      active extension of the foot, and foot posture) were used to assess results of
      functional rectus femoris transfer. One patient had an excellent result, one
      patient had a good result, and one patient had a poor result, as assessed by the
      Stanmore system. Free functional rectus femoris transfer can obtain excellent
      results in treating foot-drop and soft-tissue defects due to lower leg
      compartment syndrome and loss of all muscles of the anterior compartment. (c)

PMID- 15481040
TI  - Microsurgical second dorsal metacarpal artery cutaneous and tenocutaneous flap
      for distal finger reconstruction: anatomic study and clinical application.
AB  - In this paper, we report on the anatomical study of 34 cadaveric forearms with
      red latex injection and the clinical application of this study to 11 cases of
      microsurgical second dorsal metacarpal artery (SDMA) flaps. There were 8
      cutaneous cases and 3 tenocutaneous cases using SDMA flaps for distal finger
      reconstruction. The SDMA was classified into 2 types and 4 subtypes according to
      its anatomical origin and course. Type I (76.5%) originated from the dorsal
      branch of the radial artery at the snuffbox. Type II (23.5%) originated from the
      perforating branch of the deep palmar arch at the bases of second and third
      metacarpal bones. Diameter of the SDMA was 1.2 +/- 0.2 mm at its snuffbox origin,
      and 1.0 +/- 0.1 mm at the base of the second and third metacarpal bones.
      Clinically, microsurgical SDMA free flaps were raised and transferred for repair
      of finger injuries. Ten flaps survived completely. One flap failed due to
      thrombosis of vascular anastomosis. In conclusion, the second dorsal metacarpal
      artery is a constant and reliable vessel for microvascular anastomosis in
      microsurgical SDMA flap transfer. This flap can be used as an alternative for
      hand and finger reconstruction, and especially repair of a distal phalanx, when
      either an orthograde or retrograde island SDMA flap is unable to reach the
      defect.

PMID- 15481041
TI  - Peroneal nerve lesion after sural nerve graft harvest: an unusual complication-
      case report.
AB  - After harvesting of the sural nerve, the patient developed a partial palsy of the
      common peroneal nerve due to a lesion of the peroneal nerve and a neuroma of the
      sural nerve stump. Motor function recovered after performing neurolysis of the
      common peroneal nerve and mobilization of the neuroma. The sural nerve, in this
      case originating from the common peroneal nerve, was harvested using a nerve
      stripper and four small skin incisions. Direct lesion by the forced use of the
      nerve-stripping instrument followed by the formation of a neuroma close to the
      peroneal nerve are the suspected reasons for motor dysfunction. Although many
      authors report using a nerve stripper as a safe, less invasive method to gain
      nerve material for transplantation, we recommend lengthening the skin incision so
      as to be aware of anatomical variations and to refrain from pulling the nerve
      distally to avoid the described complications.

PMID- 15481042
TI  - Effects of Schwann cells and donor antigen on long-nerve allograft regeneration.
AB  - Nerve allotransplantation has been used successfully in human subjects to restore
      function after traumatic nerve injury and avoid subsequent limb amputation.
      However, due to the morbidity associated with nonspecific immunosuppression, this
      reconstructive approach has been limited to patients with particularly severe
      nerve injuries. It would be desirable to broaden the indications for such
      procedures through development of less toxic antirejection therapies. A miniature
      swine model of nerve transplantation was used to investigate the effects of
      preoperative ultraviolet-B (UV-B)-irradiated donor alloantigen portal venous
      infusion and injection of cultured major histocompatibility complex (MHC)-matched
      Schwann cells into the nerve graft. The transplanted ulnar nerves were harvested
      at 20 weeks. Histomorphometry showed marked enhancement in nerve regeneration
      through allografts injected with Schwann cells. Serial mixed lymphocyte assays
      demonstrated suppression of the recipient immune response to the donor antigen
      after pretreatment, but no additional neuroregenerative effect of donor
      alloantigen pretreatment.

PMID- 15481044
TI  - Supercharged reverse-flow sural flap: a new modification increasing the
      reliability of the flap.
AB  - The management of soft-tissue defects in the lower third of the leg and foot
      presents a considerable problem because of composite tissue defects, inadequate
      and tight local tissue for reconstruction, and poor circulation. Although the
      reverse sural flap is frequently preferred and is fairly reliable, some
      complications arising from the circulation may be encountered in large flaps or
      in diabetic patients. In the present study, we developed a new modification by
      supercharging the sural flap to reduce venous congestion and edema and to
      increase the reliability of the flap. We treated 3 patients (2 men and 1 woman)
      by utilizing a supercharged reverse sural flap. All flaps survived and healed
      uneventfully. We also suggest a new and more distinctive classification for
      supercharging and turbocharging, which defines the vessel type to be anastomosed
      and the relationship of the vessel to be anastomosed with the main vessel to the
      flap.

PMID- 15481045
TI  - Time-resolved fluorescence microscopy using an improved europium chelate BHHST
      for the in situ detection of Cryptosporidium and Giardia.
AB  - Fluorescent immunoconjugates prepared with the europium chelate BHHCT (4,4'
      bis(1'',1'',1'',2'',2'',3'',3''-heptafluoro-4'',6''-hexanedion-6''-yl)
      chlorosulfo-o-terphenyl) have previously been reported as suitable labels for
      time-resolved fluorescence applications. BHHCT is limited by a tendency to
      destabilize immunoglobulins when covalently bound to the protein at moderate to
      high fluorophore to protein ratios (F/P). We report a new derivative of BHHCT
      prepared by appending a short hydrophylic tether to the chlorosulfonate
      activating group on BHHCT. The new derivative, BHHST (4,4'-bis
      (1'',1'',1'',2'',2'',3'',3''-heptafluoro-4'',6''-hexanedion-6''-yl)sulfonylamino
      propyl-ester-N-succinimide-ester-o-terphenyl), was activated to bind at the
      tether terminus with a succinimide leaving group that displayed less aggressive
      coupling activity and improved storage stability. BHHST has been used to prepare
      a stable and useful immunoconjugate with the anti-Cryptosporidium monoclonal
      antibody CRY104. The BHHST immunoconjugate provides more than a 10-fold
      enhancement in the signal to noise ratio (SNR) of labeled oocyst fluorescence
      over background when observed using TRFM techniques. An immunoconjugate was also
      prepared with BHHST and (goat) anti-mouse that effectively labeled Giardia cysts
      in situ. Detection of cysts with the TRFM was achieved with an 11-fold increase
      in SNR when a gate-delay of 60 micros was employed. The storage half-life of both
      immunoconjugates is extended more than 20-fold when compared to immunoconjugates
      prepared with BHHCT.

PMID- 15481046
TI  - Microstructure of MmM(5)/Mg multi-layer hydrogen storage films prepared by
      magnetron sputtering.
AB  - Multi-layer hydrogen storage thin films with Mg and MmNi3.5(CoAlMn)1.5 (here Mm
      denotes La-rich mischmetal) as alternative layers were prepared by direct current
      magnetron sputtering. Transmission electron microscopy investigation shows that
      the microstructure of the MmNi3.5(CoAlMn)1.5 and Mg layers are significantly
      different although their deposition conditions are the same. The
      MmNi3.5(CoAlMn)1.5 layer is composed of two regions: one is an amorphous region
      approximately 4 nm thick at the bottom of the layer and the other is a
      nanocrystalline region on top of the amorphous region. The Mg layer is also
      composed of two regions: one is a randomly orientated nanocrystalline region 50
      nm thick at the bottom of the layer and the other is a columnar crystallite
      region on top of the nanocrystalline region. These Mg columnar crystallites have
      their [001] directions parallel to the growth direction and the average lateral
      size of these columnar crystallites is about 100 nm. A growth mechanism of the
      multi-layer thin films is discussed based on the experiment results.

PMID- 15481047
TI  - Use of confocal and multiphoton microscopy for the evaluation of micro-optical
      components and emitters.
AB  - We report on the application of confocal and multiphoton microscopic techniques
      for the evaluation of the latest generation of micro optical components. The
      optical emitting characteristics of arrays of matrix addressable GaN micrometer
      sized light emitting diodes (micro-LEDs) have been measured using a commercial
      confocal microscope utilising the LEDs' own emission along with reflection
      confocal microscopy to determine the surface structure. Multiphoton induced
      luminescence from the 10-20-micron diameter emitters has also been used to
      examine the structure of the device and we compare this with electrically induced
      emission. In related work, the optical properties of micro lens arrays (10-100
      micron diameter) fabricated in SiC, Sapphire, and Diamond have been determined
      using transmission confocal microscopy. Such optical microscopy techniques offer
      a simple, non-destructive method to determine the structure and performance of
      such novel devices.

PMID- 15481048
TI  - Immunohistochemistry of neuronal nitric oxide synthase and protein nitration in
      the striatum of the aged rat.
AB  - To ascertain the possible implications of the nitric oxide (NO*) producing system
      in striatal senescence, and by using immunohistochemistry and image-processing
      approaches, we describe the presence of the enzyme nitric oxide synthase (NOS),
      the NADPH-diaphorase (NADPH-d) histochemical marker, and nitrotyrosine-derived
      complexes (N-Tyr) in the striatum of adult and aged rats. The results showed
      neuronal NOS immunoreactive (nNOS-IR) aspiny medium-sized neurons and nervous
      fibres in both age groups, with no variation in the percentage of immunoreactive
      area but a significant decrease in the intensity and in the number of somata with
      age, which were not related to the observed increase with age of the striatal
      bundles of the white matter. In addition, NADPH-d activity was detected in
      neurons with morphology similar to that of the nNOS-IR cells; a decrease in the
      percentage of area per field and in the number of cells, but an increase in the
      intensity of staining for the NADPH-d histochemical marker, were detected with
      age. The number of neuronal NADPH-d somata was higher than for the nNOS-IR ones
      in both age groups. Moreover, N-Tyr-IR complexes were observed in cells (neurons
      and glia) and fibres, with a significant increase in the percentage of the area
      of immunoreaction, related to the increase of white matter, but a decrease in
      intensity for the aged group. On the other hand, we did not detect the inducible
      isoform (iNOS) either in adult or in aged rats. Taken together, these results
      support the contention that NADPH-d staining is not such an unambiguous marker
      for nNOS, and that increased protein nitration may participate in striatal aging.

PMID- 15481049
TI  - Loud noise enhances nigrostriatal dopamine toxicity induced by MDMA in mice.
AB  - The neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been
      intensely investigated due to the widespread abuse of this drug and its
      neurotoxic effects. In mice, MDMA neurotoxicity has been demonstrated for
      striatal dopamine (DA) terminals. However, the current literature has reported
      great variability in the effects induced by MDMA; this is partially due to
      changes in environmental conditions. For instance, elevated temperature and a
      crowded noisy environment markedly increase the neurotoxic effects induced by
      MDMA. The environmental factor loud noise is often present during ecstasy intake;
      however, only a few studies have analysed the consequence of a concomitant
      exposure to loud noise and ecstasy intake. In the present experimental work, we
      investigated whether nigrostriatal DA toxicity occurring after MDMA
      administration was potentiated in the presence of loud noise (100 dBA). We
      administered MDMA to C57/Black mice using a "binging" pattern for two durations
      of white noise exposure. We found a marked enhancement of MDMA toxicity (7.5
      mg/Kg x4, 2 hours apart, i.p.) in the presence of white noise exposure lasting
      for at least 6 hours. The striatal damage was assessed by assaying DA levels as
      well as the loss of tyrosine hydroxylase (TH) and the increase in striatal glial
      fibrillary acidic protein (GFAP) immunohistochemistry. Since loud noise often
      accompanies ecstasy intake, the present findings call for more in-depth studies
      aimed at disclosing the fine mechanisms underlying this enhancement.

PMID- 15481050
TI  - Histochemical evidence of the initial chondrogenesis and osteogenesis in the
      periosteum of a rib fractured model: implications of osteocyte involvement in
      periosteal chondrogenesis.
AB  - We have examined cellular events at the early stages of periosteal chondrogenesis
      and osteogenesis induced by bone fracture, using a well-standardized rib fracture
      model of the mouse. The initial cellular event was recognized as considerable
      proliferation in the deeper layer referred to as the "cambium layer" of the
      periosteum, as evidenced by numerous proliferating cell nuclear antigen-positive
      cells. The periosteal cartilage and bone were then regenerated directly from the
      region of the most-differentiated cell, i.e., mature osteoblasts of the cambium
      layer both close to and distant from the fracture site. Therefore, periosteal
      osteoblasts appeared to have the potential to differentiate into chondrogenic and
      osteoblastic lineages. CD31-positive blood vessels were uniformly localized along
      the periosteum that was regenerating cartilage and bone, being therefore
      indicative of less influence on the initiation of osteochondrogenesis. In
      contrast, however, the regenerated periosteal cartilage or bone extended from the
      cortical bones included dead or living osteocytes, respectively. Empty lacunae
      and lacunae embedded with amorphous materials were found close to the regenerated
      cartilage, while intact osteocytes persisted adjacent to the regenerated bone.
      The embedded lacunae with amorphous materials would render the tissue fluid,
      nutrients, oxygen, and several secretory factors such as dentin matrix protein-1
      impossible to be delivered to the periosteal osteoblasts that interconnect
      osteocytes via gap junctions. Our study thus provides two major clues on initial
      cellular events in response to bone fracture: the potentiality of periosteal
      osteoblastic differentiation into a chondrogenic lineage, and a putative
      involvement of osteocytes in periosteal cartilage and bone regeneration.

PMID- 15481051
TI  - Macrophagic response to human mesenchymal stem cell and poly(epsilon
      caprolactone) implantation in nonobese diabetic/severe combined immunodeficient
      mice.
AB  - Nonobese diabetic, severe combined immunodeficient (NOD/SCID) mice are
      extensively used to assess in vivo potentials for human cellular differentiation,
      development, and neophysiology. They are not only deficient in T and B cells, but
      also exhibit macrophage dysfunction and an absence of circulating complement.
      However, the survival of engrafted human mesenchymal stem cells (hMSCs) is
      limited and minimal mature bone tissue develops from implanted hMSCs in this
      model. The aim of the present study was to investigate the response to such
      implants in NOD/SCID mice. To this end, hMSCs genetically marked with enhanced
      green fluorescent protein, a biodegradable polymer, poly(epsilon-caprolactone)
      (PCL), and a bioconstruct incorporating the enhanced green fluorescent protein
      labeled hMSCs with PCL after culture together for 3 weeks in vitro, were
      implanted into NOD/SCID mice and followed for up to 10 weeks.
      Monocytes/macrophages appeared to be the major invading cell type in all the
      implants and remained in the materials regardless of whether or not hMSCs were
      present over the time periods studied. When the hMSCs were implanted without the
      PCL scaffold, host macrophage invasion was also observed with the majority of
      hMSCs being eliminated within 2 weeks. Multinuclear giant cells or foreign body
      giant cells were seen in the cases of PCL implantation. These cells slowly
      infiltrated into the central core of the materials over a 10-week period of
      implantation with neutrophils and mast cells also being observed. In conclusion,
      in NOD/SCID mice, monocytes/macrophages still effectively respond to the
      implantation of xenografts and biopolymers with functional migration,
      phagocytosis, adhesion, foreign body recognition and formation of multinuclear
      giant cells, or foreign body giant cells. Thus, these animals still retain a
      level of innate immune responsiveness to these implantations and in addition may
      provoke a physiological environment that is unsuitable for extensive
      intramembranous ossification by engrafted hMSCs.

PMID- 15481052
TI  - Characterization of ovarian nuclei with the parameter of power ratio.
AB  - The nucleoli and chromatin clumps of ovarian cells contain important features in
      discriminating malignant cells from normal ones. In geometric properties, the
      ovarian nucleoli and chromatin clumps appear as irregularly shaped dark spots in
      the nuclear images from specimens immunohistochemically stained with antibody to
      Mib-1. Malignant cells often have more active and larger nucleoli and chromatin
      clumps. However, estimating the size of the nucleoli or chromatin clumps is a
      difficult task since it is not easy to recognize and accurately separate the
      regions of nucleoli and chromatin clumps from the rest of the nuclei that are
      highly irregular and variant in contents and intensities. In this paper, we
      develop a method to derive a parameter called power ratio that is proportionally
      related to the size of nucleoli and chromatin clumps based on an ideal nuclear
      model without the region segmentation of nucleoli or chromatin clumps. Results of
      characterization of the parameter and comparison between malignant and normal
      cells are provided.

PMID- 15481053
TI  - Fibronectin adsorption on surface-activated poly(dimethylsiloxane) and its effect
      on cellular function.
AB  - This article reports that surface modification of poly(dimethylsiloxane) (PDMS)
      influences fibronectin (Fn) adsorption and enhances cell attachment. Controlled
      adsorption of Fn on chemically activated polymer substrates is known to influence
      cellular function. Thin films of PDMS were spun cast on silicon wafers to obtain
      homogeneous and molecularly smooth surfaces. The films were made hydrophilic by
      exposure to ultraviolet ozone activation (PDMS*). The films then were
      characterized by contact angle goniometry, ellipsometry, atomic force microscopy
      (AFM), Rutherford backscattering spectrometry and X-ray photoelectron
      spectroscopy. Contact angle measurements indicated higher hydrophobicity of the
      nonactivated PDMS substrates than PDMS*. AFM scans of the substrates indicated
      higher surface roughness of PDMS* (Ra = 0.55 nm) than PDMS (Ra = 0.25 nm).
      Although Fn surface density (Gamma) was slightly higher on PDMS than on PDMS*,
      due to hydrophobic interactions between substrate and Fn, cell function was
      greatly enhanced on the Fn-coated PDMS* (PDMS*-Fn) than on PDMS (PDMS-Fn). Higher
      attachment of MC3T3-E1 osteoblast-like cells was observed on PDMS*-Fn than on
      PDMS-Fn. Moreover, cell spreading and cytoskeleton organization after 72 h was
      clearly favored on the Fn-coated PDMS* surfaces.

PMID- 15481054
TI  - Crystal structure of a conserved hypothetical protein TT1751 from Thermus
      thermophilus HB8.

PMID- 15481055
TI  - Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine,
      doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult
      acute lymphocytic leukemia.
AB  - BACKGROUND: Modern intensive chemotherapy regimens have improved the prognosis
      for patients with adult acute lymphocytic leukemia (ALL). With these regimens,
      the complete response rates are now reported to be > 80%, and the long-term
      survival rates range from 30% to 45%. The current analysis updated the long-term
      results with the original hyperfractionated cyclophosphamide, vincristine,
      doxorubicin, and dexamethasone (Hyper-CVAD) program, with a median follow-up time
      of 63 months. METHODS: Between 1992 and 2000, 288 patients were treated with
      Hyper-CVAD. The median age of the patients was 40 years, and 59 patients (20%)
      were > or = age 60 years. The incidence of Philadelphia chromosome (Ph)-positive
      ALL was 17%, and the incidence of of T-cell ALL was 13%. RESULTS: A complete
      response (CR) was achieved in 92% of patients. The induction mortality rate was
      5% (2% if the patient's age was < 60 years, and 15% if the patient's age was > or
      = 60 years). With a median follow-up time of 63 months, the 5-year survival rate
      was 38% and the 5-year CR duration rate was 38%. Multivariate analysis of
      prognostic factors for CR duration identified the following adverse factors: age
      > or = 45 years, leukocytosis > or = 50 x 10(9)/L, poor performance status (an
      Eastern Cooperative Oncology Group score of 3-4), Ph-positive disease, French
      American-British L2 morphology, > 1 course to achieve CR, and Day 14 bone marrow
      blasts > 5%. Patients were divided into low-risk (risk score 0-1; 37%),
      intermediate risk (risk score 2-3; 36%), and poor-risk groups (risk score > or =
      4; 27%) with 5-year CR duration rates of 52%, 37%, and 10%, respectively.
      CONCLUSIONS: Compared with the previous VAD regimens, Hyper-CVAD was associated
      with significantly better CR rates, CR duration, and survival. The long-term
      follow-up results of Hyper-CVAD were favorable. Comparison of Hyper-CVAD with
      other established adult ALL regimens is warranted.

PMID- 15481057
TI  - Cellular alignment by grafted adhesion peptide surface density gradients.
AB  - The extracellular matrix and extracellular matrix-associated proteins play a
      major role in growth and differentiation of tissues and organs. To date, few
      methods have been developed that allow researchers to examine the affect of
      surface density gradients of adhesion molecules in a controlled manner.
      Fibroblasts cultured on surfaces with a surface density gradient of RGD peptide
      aligned parallel to the gradient while fibroblasts on constant density RGD
      surfaces spread but did not align as has been shown in numerous earlier studies.
      Not only did fibroblasts align on the gradient surfaces, but they also showed
      significantly greater elongation than on constant density peptide surfaces or on
      control surfaces. This type of method is easy to replicate and can be used by
      laboratories interested in investigating alignment of various cell types without
      mechanical force or other stimulation, and without cell-cell interaction or for
      investigation of affects of surface density gradients of molecules on cellular
      biochemistry and biophysics. This method also has potential applications for
      developing scaffolds for tissue engineering applications where cellular alignment
      is necessary.

PMID- 15481058
TI  - Conservative treatment of invasive bladder carcinoma by transurethral resection,
      protracted intravenous infusion chemotherapy, and hyperfractionated radiotherapy:
      long term results.
AB  - BACKGROUND: Organ preservation has been investigated in patients with muscle
      invasive bladder carcinoma over the past decades as an alternative to radical
      cystectomy. The majority of studies reported that trimodal schedules, including
      transurethral resection of bladder tumor (TURB), radiotherapy (RT), and
      chemotherapy, are a feasible and safe organ-sparing approach without deferring
      the survival probability. However, to the authors' knowledge the best combination
      of RT and chemotherapy has yet to be well defined. The current study evaluated
      the long-term results of a schedule of concurrent cisplatin and 5-fluorouracil (5
      FU) administered as protracted intravenous infusions (PVI) during
      hyperfractionated radiotherapy (HFRT) with organ-sparing intent in patients with
      infiltrating transitional cell carcinoma of the bladder (TCCB). METHODS: Seventy
      seven patients with a classification of T2-T4aN0M0 TCCB were enrolled in the
      current study. After a complete TURB and bladder mapping, 42 of 77 patients
      underwent 2 cycles of induction chemotherapy. All 77 patients underwent HFRT and
      a schedule of cisplatin (4-6 mg/m(2) per day) and 5-FU (180-220 mg/m(2) per day)
      as concomitant PVI (radiochemotherapy [RCT]). Six to 8 weeks after RCT, patient
      response was evaluated by computed tomography scan, urine cytology, and TURB.
      Patients who achieved a complete response (CR) were followed at regular
      intervals. For patients with residual or recurrent invasive tumor, salvage
      cystectomy was recommended. RESULTS: Seventy-two patients were evaluable for
      response: 65 achieved a CR (90.3%) and 7 (9.7%) achieved a partial response. No
      significant difference was observed for the different prognostic factors with the
      exception of stage of disease (T2 [95.7%] vs. T3-T4a [80.0%]; P = 0.04). The
      observed toxicity, mainly hematologic, was higher among the patients who received
      induction chemotherapy compared with the patients who did not receive induction
      chemotherapy, even though the difference was not statistically significant. After
      a median follow-up of 82.2 months (range, 30-138 months), 44 of 65 (57.1%)
      patients who achieved a CR were alive. Of these 44 patients, 33 had tumor-free
      bladders. The 5-year overall, bladder-intact, tumor-specific, disease-free, and
      cystectomy-free survival rates for all 77 patients were 58.5%, 46.6%, 75.0%,
      53.5%, and 76.1%, respectively. No associations were observed in overall and
      tumor-specific survival with different prognostic factors. CONCLUSIONS: Combined
      treatment appeared to provide high response rates and can be offered as an
      alternative option to radical cystectomy in selected patients who refuse or are
      unsuitable for surgery.

PMID- 15481059
TI  - Amniotic membrane graft: histopathological findings in five cases.
AB  - Amniotic membrane transplantation (AMT) is an effective treatment for ocular
      surface reconstruction; however, the mechanisms through which amniotic membrane
      (AM) exerts its effects as well as its fate after transplantation have not been
      entirely elucidated and have been investigated only in part. We evaluate the
      integration of AM in the host cornea in five patients who underwent AMT as the
      result of Bowen's disease, band keratopathy, radio- or cryotherapy-induced
      keratopathy, chemical burn or post-herpetic deep corneal ulcer with
      descemetocele. Due to persistent opacification in four cases and a progressing
      tumor in one case, penetrating keratoplasty (PK) and enucleation were performed
      as early as 2 months and up to 20 months after AMT. The corneas were analyzed
      histopathologically. To evaluate AM remnants, corneas were stained with periodic
      acid Schiff's reaction (PAS), Alcian blue, and Gomory and Masson trichrome;
      immunostaining including collagens III and IV antibodies was also performed. None
      of the corneas showed remnants of AM. In all cases, we observed discontinuity of
      Bowman's membrane. In three cases, the corneal epithelium was completely
      restored, ranging from three to six cell layers. In the other two cases, we
      detected an intense inflammatory reaction with rich neovascularization; the
      epithelial surface of the central cornea was completely restored, while at the
      periphery of the cornea goblet mucus-producing cells were present. Although
      clinically useful in all cases, restoration of a stable corneal epithelium
      through AMT is limited by the extent and severity of limbal stem cell deficiency
      (LSCD). The lack of histologically documented AM remnants in our cases seems to
      explain the efficacy of AMT more through its biological properties than through
      its mechanical properties.

PMID- 15481060
TI  - Incidence of multiple myeloma in Olmsted County, Minnesota: Trend over 6 decades.
AB  - BACKGROUND: Previous studies have indicated that the incidence and mortality
      rates for multiple myeloma have increased in the United States. The authors
      reported on the incidence of multiple myeloma in Olmsted County, Minnesota,
      between 1991 and 2001 and on trends in multiple myeloma incidence over the last
      56 years. METHODS: Using the files of the Mayo Clinic and the Olmsted Medical
      Center (Rochester, MN), the authors identified all residents of Olmsted County
      who had multiple myeloma, suspected myeloma, or a related disorder. Reports of
      all laboratory determinations, in addition to autopsy findings and death
      certificates, were obtained. The criteria for the diagnosis of multiple myeloma
      have not changed during the last 6 decades. RESULTS: All but 1 of the 47
      residents with multiple myeloma first diagnosed between 1991 and 2001 were
      recognized antemortem. Fifty-five percent had a previous monoclonal gammopathy of
      undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma
      before multiple myeloma was diagnosed. From 1991 to 2001, the overall annual
      incidence rate, age-adjusted to the 2000 U.S. population, was 4.3 per 100,000
      (95% confidence interval, 3.0-5.5 per 100,000). Poisson regression analysis
      showed no statistically significant trend in Olmsted County incidence rates over
      56 years. In similar fashion, the authors adjusted multiple myeloma incidence
      rates from nine other studies worldwide for which adequate data were available
      and documented similar findings in each case, except for one study that included
      patients with smoldering multiple myeloma. CONCLUSIONS: The overall incidence of
      multiple myeloma in Olmsted County, Minnesota, has not changed in almost 6
      decades. The apparent increase in incidence elsewhere is unexplained but probably
      is attributable to improvements in diagnostic techniques, particularly in older
      patients.

PMID- 15481061
TI  - Primitive neuroectodermal tumor (PNET) of the uterus in a renal allograft
      patient: a case report.
AB  - The incidence of malignancy after renal transplant has been reported to range
      from 4% to 18%. Tumors of the skin and lip tend to be the most common with non
      Hodgkin lymphoma comprising 20% of all neoplasms. Primitive neuroectodermal
      tumors (PNET) are collectively described as being a part of the Ewing sarcoma
      family of tumors. PNET occur more commonly in the second decade of life,
      predominantly affecting Whites and Hispanics, and rarely occur in individuals of
      African or Asian descent. The most common primary site of involvement is along
      the central axis, particularly the chest (Askin tumor), but it can arise in any
      soft tissue. PNET also occur in the head and neck. PNET involving the cervix,
      urinary bladder, uterus, and vagina have been reported. We describe a case of a
      15-year-old female who, 9 years after receiving a living related renal
      transplant, developed a post-transplant PNET of the uterus.

PMID- 15481062
TI  - Intravenous 6-mercaptopurine decreases salvage after relapse in childhood acute
      lymphoblastic leukemia: a report from the Children's Cancer Group study CCG 1922.
AB  - PURPOSE: To compare outcomes of patients with NCI standard risk acute
      lymphoblastic leukemia (ALL) who relapsed after being randomized to receive
      either oral or intravenous 6-mercaptopurine (6MP) in the Children's Cancer Group
      study CCG 1922. PATIENTS AND METHODS: CCG 1922 accrued patients from March 1993
      to August 1995. A total of 1,060 patients were randomly assigned to four
      treatment groups: oral 6MP plus prednisone (OP), intravenous 6MP plus prednisone
      (IP), oral 6MP plus dexamethasone (OD), and intravenous 6MP plus dexamethasone
      (ID). During the 2nd through 4th month of therapy groups OP and OD were treated
      with 75 mg/m(2)/day of oral 6MP for 70 days and groups IP and ID with 1,000
      mg/m(2)/week of intravenous 6MP over 10 hr for 11 doses. All patients received a
      single delayed intensification and all received oral 6MP in maintenance. RESULTS:
      Patients randomized to oral 6MP had significantly better 5-year overall survival
      (96 +/- 1% vs. 92 +/- 1%; P = 0.008). There was, however, no statistically
      significant difference in the event-free survival (EFS). Of the 179 patients who
      relapsed, 84 had a second or later event and 68 have died. Forty of the 84 second
      events were a death. Survival after relapse was significantly greater for
      patients randomized to oral 6MP during consolidation than those receiving
      intravenous 6MP (P = 0.002, log rank test) with 4-year survival post-relapse of
      67 +/- 6% vs. 48 +/- 6%. The steroid randomization had no influence on outcome.
      Post-relapse therapy details are not available and if different between groups
      may have influenced the outcome. CONCLUSION: Treatment with intravenous 6MP
      during a brief period of total therapy had a significant negative impact on the
      prognosis in childhood ALL even though oral 6MP was used during maintenance.

PMID- 15481064
TI  - Amniotic membrane transplantation in ocular surface disorders.
AB  - Chronic ocular surface disorders, which can result in severe functional
      impairment, have been viewed for decades as untreatable diseases. In 1995, the
      reintroduction of amniotic membrane transplantation (AMT), either alone or
      associated with limbal stem cell transplantation, has offered new hope of using
      tissue and cell therapy strategies to repair ocular surface disorders. Amniotic
      membrane (AM) has been found to exert its effects by acting as a substrate for
      the growth of ocular surface epithelia, by suppressing inflammation and scarring
      and by serving as an anti-microbial barrier. Moreover, AM has recently been used
      as a substrate for ex vivo expansion of corneal epithelial cells for ocular
      surface reconstruction. Notwithstanding the substantial agreement among Authors
      regarding its clinical efficacy, there are still many uncertainties regarding the
      fate of grafted AM and consequently the mechanisms through which it exerts its
      long-term effects. Further studies including controlled clinical trials with
      numerous cases are required to understand which ocular surface conditions are
      certain to benefit from AM transplantation and how its mechanical properties
      interact with the mediators produced to favor ocular surface reconstruction.

PMID- 15481063
TI  - Integrin alpha2beta1 modulates EGF stimulation of Rho GTPase-dependent
      morphological changes in adherent human rhabdomyosarcoma RD cells.
AB  - The ability of cells to undergo shape changes is essential for diverse cellular
      functions including cell growth, differentiation, and movement. The present study
      examines how an integration of the function of alpha2beta1 integrin with that of
      the receptor for epidermal growth factor (EGFR) modulates EGF-stimulated
      morphological changes in human rhabdomyosarcoma RD transfectant cells. Upon EGF
      stimulation, RD transfectant cells that lacked alpha2beta1 integrin expression
      (RDpF) underwent contraction; in contrast, expression of alpha2beta1 on RD cells
      (RDX2C2) resulted in transient cell spreading. Integrin alpha2 cytoplasmic domain
      played a critical role in the observed alpha2beta1-mediated conversion from a
      cell rounding to a cell spreading phenotype. Thus, the expression of an alpha2
      cytoplasmic domain deletion variant (X2C0) or a chimeric alpha2beta1 containing
      the cytoplasmic domain of alpha4 (X2C4) or alpha5 (X2C5), instead of alpha2,
      failed to mediate spreading upon EGF stimulation. Using dominant negative (DN)
      mutants of RhoGTPases, results revealed that RhoA activation was required for
      both EGF-stimulated responses of cell rounding and spreading, Cdc42 functioned in
      the re-spreading of cells after undergoing EGF-stimulated contraction, and Rac1
      was required in alpha2beta1-mediated RD cell spreading. Therefore, alpha2beta1
      integrin function can switch the Rho GTPase-dependent cell shape changes in RD
      cells from an EGF-stimulated cell contraction to a spreading morphology.
      Together, results show that integrin alpha2 cytoplasmic domain plays an
      indispensable role in the ability of integrin alpha2beta1 to modulate EGF
      stimulation of Rho-GTPase-dependent morphological changes in RD cells.

PMID- 15481065
TI  - A randomized, controlled, clinical trial of activity therapy for apathy in
      patients with dementia residing in long-term care.
AB  - BACKGROUND: Apathy is a common symptom in patients with dementia and has adverse
      consequences for patients and caregivers. Most treatments for apathy,
      particularly non-pharmacologic interventions, have not been evaluated in
      controlled trials. OBJECTIVES: This study evaluated the efficacy of a kit-based
      activity intervention, compared to a time and attention control (one-on-one
      meetings with an activity therapist) in reducing apathy and improving quality of
      life in 37 patients with dementia. METHODS: The design was a randomized,
      controlled, partially masked clinical trial. All outcome measures were
      administered at baseline and follow-up. The primary outcome measure was the
      apathy score of the Neuropsychiatric Inventory (NPI). Other outcome measures were
      the NPI total score, the Alzheimer Disease Related Quality of Life scale(ADQRL),
      and the Copper Ridge Activity Index (CRAI). RESULTS: There was a significant
      reduction in NPI apathy scores in both treatment groups. The only significant
      difference between the two treatment groups was a modest advantage for the
      control intervention on the CRAI cueing subscale (p = 0.027), but not on the
      other CRAI subscales. There was also a greater within group improvement in
      quality of life ratings in the control intervention (p=0.03). CONCLUSIONS:
      Despite the substantial improvement in apathy scores during the course of the
      study, there was no clear advantage to the reminiscence-based intervention over
      the time and attention, one-on-one control intervention. More research is needed
      to develop specific behavioral interventions for apathy in patients with
      dementia.

PMID- 15481066
TI  - Nitric oxide specifically reduces the permeability of Cx37-containing gap
      junctions to small molecules.
AB  - Gap junction intercellular communication (GJIC) plays a significant role in the
      vascular system. Regulation of GJIC is a dynamic process, with alterations in
      connexin (Cx) protein expression and post-translational modification as
      contributing mechanisms. We hypothesized that the endothelial autacoid nitric
      oxide (NO) would reduce dye coupling in human umbilical vein endothelial cells
      (HUVECs). In our subsequent experiments, we sought to isolate the specific Cx
      isoform(s) targeted by NO or NO-activated signaling pathways. Since HUVEC cells
      variably express three Cx (Cx37, Cx40, and Cx43), this latter aim required the
      use of transfected HeLa cells (HeLaCx37, HeLaCx43), which do not express Cx
      proteins in their wild type form. Dye coupling was measured by injecting
      fluorescent dye (e.g., Alexa Fluor 488) into a single cell and determining the
      number of stained adjacent cells. Application of the NO donor SNAP (2 microM, 20
      min) reduced dye coupling in HUVEC by 30%. In HeLa cells, SNAP did not reduce dye
      transfer of cells expressing Cx43, but decreased the dye transfer from Cx37
      expressing cells to Cx43-expressing cells by 76%. The effect of SNAP on dye
      coupling was not mediated via cGMP. In contrast to its effect on dye coupling,
      SNAP had no effect on electrical coupling, measured by a double patch clamp in
      whole cell mode. Our results demonstrate that NO inhibits the intercellular
      transfer of small molecules by a specific influence on Cx37, suggesting a
      potential role of NO in controlling certain aspects of vascular GJIC.

PMID- 15481067
TI  - The feasibility and effectiveness of brief interventions to prevent depression in
      older subjects: a systematic review.
AB  - OBJECTIVES: To explore the feasibility and effectiveness of brief interventions
      to prevent depression in older subjects. METHOD: MEDLINE, PsycINFO and HealthStar
      were searched for potentially relevant articles published from January 1966 to
      June 2003, January 1974 to June 2003 and January 1975 to June 2003, respectively.
      The bibliographies of relevant articles were searched for additional references.
      Ten studies met the following five inclusion criteria: original research,
      subjects mean age 50 years or more, controlled trial of a brief (<12 weeks)
      intervention to prevent depression, determination of depression status 12 months
      or more after enrolment, use of an acceptable definition of depression. The
      validity of studies was assessed according to six criteria. To examine
      feasibility we tabulated study enrolment, completion and compliance rates. To
      examine effectiveness we tabulated differences in depression symptom outcome
      scores between intervention and control groups or, when possible, absolute (ARR)
      and relative (RRR) risk reductions for depression. RESULTS: Only two of the ten
      trials met all of the validity criteria. Study enrolment rates were 21 to 100%
      (median 72.5%); study completion rates were 46% to 100% (median 85%); compliance
      rates were 29% to 100% (median 87%). Five of the ten trials had positive results:
      in two trials there were statistically significant differences in depression
      symptom outcome scores favoring the intervention group; in three trials ARRs were
      2.3% to 45% (median 17%); RRRs were 45% to 71% (median 61%). CONCLUSIONS: Some
      types of brief interventions appear to have the potential to prevent depression
      in older subjects. Despite the methodologic limitations of the trials and this
      systematic review, these findings may guide efforts to develop and evaluate brief
      interventions to prevent depression in this population.

PMID- 15481068
TI  - A comparison of the effects of Snoezelen and reminiscence therapy on the agitated
      behaviour of patients with dementia.
AB  - BACKGROUND: Behavioural disturbance, such as agitation, is a common feature of
      dementia, and causes significant problems and distress for carers. Snoezelen is
      increasingly used with people who have dementia, but there is limited evidence of
      its efficacy. OBJECTIVE: This crossover randomised controlled study aimed to
      evaluate the effect of Snoezelen on the mood and behaviour of patients with
      dementia, in comparison to the effect of an established and accepted
      intervention, reminiscence therapy. METHODS: Twenty patients with dementia and
      significant agitated behaviour, received three sessions each of Snoezelen and
      reminiscence. The effects were assessed using measures of observed agitated
      behaviour and heart rate over the course of the sessions, and mood and behaviour
      during the sessions. RESULTS: Both interventions had a positive effect. Snoezelen
      was no more beneficial than reminiscence in terms of effecting a significant
      reduction in agitated behaviour or heart rate. There was considerable variation
      in the way individuals responded to each intervention. Snoezelen may have a more
      positive effect than reminiscence, but due to the observed differences between
      the interventions being small, and the small number of subjects, this advantage
      was not demonstrated statistically. CONCLUSIONS: Further research, with larger
      numbers of subjects, and an appropriate control is required to establish the
      benefits of Snoezelen for people at different stages of dementia, and to identify
      any benefits additional to those derived from increased staff attention.

PMID- 15481069
TI  - A systematic review of the utility of self-report alcohol screening instruments
      in the elderly.
AB  - BACKGROUND: Effective screening instruments are needed for the detection of
      alcohol use disorders (AUDs) in the elderly, in view of the significant physical,
      psychological and social problems associated with this phenomenon. METHODS: This
      paper provides details on the different self-report alcohol screening instruments
      that have been studied in the elderly, describing both the instruments themselves
      and their effectiveness as screening instruments for AUDs in different elderly
      populations. RESULTS: The vast majority of studies reviewed were carried out in
      the US, and a high proportion of these were carried out in Veterans
      Administrations institutions, thus limiting the generalizability of results. The
      CAGE was the most widely studied screening instrument, followed by the MAST or
      variations of the MAST, the AUDIT and variations of the AUDIT, and other
      screening instruments. Sensitivity and specificity of these instruments varied
      widely, depending on the prevalence of AUDs in the population being studied, the
      clinical characteristics of the population and the type of AUD being detected.
      The CAGE performed poorly in psychiatric populations but a newer instrument, the
      AUDIT-5, has had promising results to date. No studies focussed on elderly people
      with cognitive impairment, and there is a need for research in this area.
      CONCLUSIONS: Ease of use, patient acceptability, sensitivity and specificity must
      all be considered when selecting a self-report alcohol screening instrument for
      use in the elderly. Furthermore, the prevalence of AUDs in the population and the
      clinical characteristics of that population must also be taken into account.

PMID- 15481070
TI  - Older women's cognitive and affective response to moderate drinking.
AB  - OBJECTIVE: In this paper we investigated the question, how do older women who
      drink moderate amounts of alcohol differ from those who do not drink on
      measurements of cognitive function, memory, affect and health? METHODS: The
      nonprobability sample of female participants (n=182) averaged 75 years of age and
      had a Mini Mental State Examination scores of 28. The participants were asked to
      indicate whether they drank alcohol or abstained (yes/no) and if they indicated
      that they did drink, to describe how many drinks they consumed in a given period
      of time (day/week/month). RESULTS: None of the participants acknowledged drinking
      more than 2 drinks a day. Caucasian women had the largest number of moderate
      drinkers (53% vs 47%), while the majority of African-American and Hispanic women
      reported not drinking. The moderate drinkers reported less depression, had higher
      self-reported health, performed better on instrumental everyday tasks, had
      stronger memory self-efficacy, and used more strategies to improve memory
      performance. In addition, these women had higher performance on tests of
      executive function: attention, concentration, psychomotor skills, verbal
      associative capacities, and oral fluency. CONCLUSIONS: The circumstances under
      which people drink are complex and were not evaluated in this study. Therefore,
      rather than endorsing drinking behavior, these findings suggest that future
      research might examine why elders make the decision to drink, the circumstances
      that predispose women to drink (alone/with others), and other qualities that
      characterize female drinkers over the age of 65.

PMID- 15481071
TI  - Langerhans cell histiocytosis with central nervous system involvement: follow-up
      by FDG-PET during treatment with cladribine.
AB  - The prognosis of patients with Langerhans cell histiocytosis (LCH) involving the
      central nervous system (CNS) is generally poor, despite reports of clinical
      responses to chemotherapy, surgery, and radiation. We report on a patient with a
      20-year history of relapsing multisystem LCH who developed progressive
      neuropsychiatric symptoms, including diplopia, ataxia, and mental deterioration.
      There was a regression of lesions in the brain stem and cerebellum following
      chemotherapy with cladribine (2-CdA) as evidenced by positron emission tomography
      (PET) scans. In conclusion, our experience is encouraging for the use of
      cladribine in CNS LCH. PET may be a useful modality for the monitoring of CNS
      disease activity in LCH and provides additional information in comparison with
      NMR imaging.

PMID- 15481072
TI  - Executive functioning in psychogeriatric patients: scalability and construct
      validity of the Behavioral Dyscontrol Scale (BDS).
AB  - OBJECTIVES: Item response theory was used to test the scalability of the
      Behavioral Dyscontrol Scale (BDS). The BDS assesses the control of voluntary
      movement, working memory and self-monitoring. Construct validity of the BDS was
      examined with confirmatory factor analysis. METHODS: The BDS was administered to
      693 consecutive, community-dwelling visitors of a psychogeriatric day unit (424
      women and 269 men between the ages of 50 and 94). Unidimensionality of the BDS
      was determined using Mokken's scalogram analysis. The BDS total score was
      correlated with other measures of executive function (Expanded Mental Control
      Test, category fluency, and alternating graphical sequences) and with episodic
      memory tests of orientation and delayed picture recognition in order to test a
      model of distinct latent constructs of executive functioning and episodic memory.
      RESULTS: Loevinger's scalability coefficient H was 0.58 for the complete item set
      of the BDS. Subjects can be ordered on the latent dimension of executive ability.
      The first eight items of the BDS (deleting the insight rating) satisfy the
      assumption of non-intersecting item characteristic curves (double monotonicity)
      which means that they comprise a Guttman-ordered scale (H = 0.60). The BDS and
      three independent measures of executive control strongly correlated with a latent
      construct of executive functioning (convergent validity). However, discriminant
      relations with a nonexecutive construct (recognition memory and orientation)
      could not be demonstrated. CONCLUSIONS: The BDS satisfies criteria for
      scalability according to item response theory. Its construct validity as an
      executive-specific measure is as yet unclear.

PMID- 15481073
TI  - Neuropsychological characteristics of mild vascular cognitive impairment and
      dementia after stroke.
AB  - BACKGROUND: Post-stroke cognitive impairment is frequent, with characteristic
      impairments of attentional and executive performance. OBJECTIVE: The study aims
      to determine whether the profile and severity of impairment in vascular Cognitive
      Impairment No Dementia (vascular CIND) is intermediate between that seen in
      stroke patients without significant cognitive impairment and patients with post
      stroke dementia and thus to establish if the potential value of vascular CIND is
      a useful concept for predicting further cognitive decline and dementia in stroke
      patients. METHODS: Stroke patients (n=381) > 75 were recruited from
      representative hospital-based stroke registers in Tyneside and Wearside, UK.
      Sixty six age matched controls were also recruited. A detailed battery of
      neuropsychological assessments was completed 3 months post stroke. RESULTS:
      Deficits of attention (z=5.7; p <0.0001) and executive function (z=5.9; p
      <0.0001) were seen even in stroke patients without vascular CIND, compared to
      controls. However, stroke patients with CIND were significantly more impaired
      again on tests of executive function (z=10.3; p <0.0001) compared to those not
      meeting CIND criteria; and also had greater impairments of memory (z=10.4; p
      <0.0001) and language expression (z=10.1; p <0.0001). A similar overall profile
      of deficits was evident in the CIND and the dementia group, but specific deficits
      were significantly more pronounced in those with dementia, particularly in
      orientation (z=7.2; p <0.0001) and memory (z=5.8; p <0.0001). CONCLUSIONS: The
      current study indicates that attentional and executive impairments are frequent
      in stroke patients, but deficits of memory, orientation and language are more
      indicative of CIND and dementia. Further longitudinal studies are required to
      clarify the relationship between specific lesions and the progression of specific
      cognitive deficits in post-stroke patients.

PMID- 15481074
TI  - Measuring disability in patients with neurodegenerative disease using the
      'Yesterday Interview'.
AB  - OBJECTIVES: To illustrate the use of time-budget methodology as a means of
      measuring disability within the framework of the World Health Organisation (WHO)
      International Classification of Functioning, Disability and Health (ICF) in a
      mixed group of patients with neurodegenerative disease. METHODS: A semi
      structured interview method (the 'Yesterday Interview') was used to reconstruct
      the preceding 24-hour period in terms of activity, social and environmental
      context, and subjective enjoyment. Data were collected on 40 elderly control
      subjects and a sample of 99 community based patients diagnosed with either
      Parkinson's disease without or with dementia, Alzheimer's disease, Dementia with
      Lewy bodies, Progressive Supranuclear Palsy or Multiple System Atrophy. All
      participants were seen in their own home. The results were translated
      hierarchically into the ICF framework of disability domains, and further into a
      higher level formulation based on the constructs of discretionary/obligatory
      activity. RESULTS: Disability profiles were obtained for the patient group as a
      whole and for the individual disorders. Restricted patterns of time-use were
      noted across a range of domains encompassing both obligatory and discretionary
      activity, and accompanied by a significant increase in passive activity such as
      day-time sleeping or sitting in front of the television. The data also
      illustrated the restrictions in both the social and environmental contexts of the
      patient's lives, and the diminished levels of subjective enjoyment associated
      with their pattern of daily time-use. With the exception of time spent on
      discretionary activities, these various indices were significantly associated
      with standard clinical measures disability. CONCLUSIONS: With further studies to
      assess reliability and validity, time-use and contextual data obtained from
      structured interviews may provide a useful means of measuring disability within
      the ICF framework in patients with degenerative neurological disease.

PMID- 15481075
TI  - Behavioural and psychological syndromes in Alzheimer's disease.
AB  - OBJECTIVES: The origins of behavioural and psychological symptoms of dementia are
      still poorly understood. By focusing on piecemeal behaviours as opposed to more
      robust syndrome change valid biological correlates may be overlooked. Our
      understanding of BPSD via the identification of neuropsychiatric syndromes.
      METHODS: We recruited 435 subjects from old age psychiatry and elderly care
      memory outpatient clinics fulfilling the criteria for diagnosis of probable
      Alzheimer's disease. Behavioural and psychological symptoms were assessed using
      the Neuropsychiatric Inventory. Principal components factor analysis was carried
      out on the composite scores of the 12 symptom domains to identify behavioural
      syndromes (factors). Results were confirmed by performing three different
      rotations: Varimax, Equamax and Quartimax. RESULTS: Four factors were identified
      (which accounted for 57% of the variance): 'affect' factor-depression/dysphoria,
      anxiety, irritability/lability and agitation/aggression; 'physical behaviour'
      factor-apathy, aberrant motor behaviour, sleep disturbance and appetite/eating
      disturbance; 'psychosis' factor-delusions and hallucinations; 'hypomania' factor
      disinhibition and elation/euphoria. These groups were unchanged when different
      methods of rotation were used. CONCLUSIONS: We report novel observations that
      agitation/aggression/irritability cluster within a depressive symptom factor and
      apathy is found within a physical behaviour factor.

PMID- 15481076
TI  - The relationship between non-cognitive symptoms and functional impairment in
      Alzheimer's disease.
AB  - OBJECTIVE: Cognitive impairment is an important determinant for functional
      impairment in Alzheimer's disease. The role of non-cognitive symptom is
      uncertain. The objective of this study was to investigate the role of non
      cognitive symptoms as predictive factors for functional outcome in A.D. METHODS:
      This was a retrospective study. Subjects were recruited from the Memory Clinic in
      Queen Mary Hospital over a two years period. Patients with diagnosis of probable
      A.D. by NINCDS-ADRDA were identified. Demographic data, Folstein Mini-Mental
      Status Examination (MMSE), Clinical Dementia Rating (CDR), Neuropsychiatric
      inventory (NPI), Barthel activities of daily living (ADL) as well as Lawton's
      Instrumental activities of daily living (IADL) were retrieved. RESULTS: 100
      patients were identified. Univariate analysis identified statistically
      significant correlation between hallucination and disinhibition score with
      Barthel Index (r=-0.43, p <0.001; r=-0.30, p=0.002 respectively); hallucination
      and aberrant motor act score with Lawton's IADL (r=-0.21, p=0.038; r=-0.21,
      p=0.038). MMSE was statistical significantly correlated with the above two
      functional scores. NPI was not statistical significantly correlated with any one
      of the functional measures. Multivariate regression analyses showed that
      hallucination score was an independent predictive factors for the Barthel index
      but not for the Lawton's IADL. MMSE score was identified to be independent
      predictive factor for all functional measures. CONCLUSIONS: Global cognitive
      impairment and hallucination was an important independent predictive factor for
      functional outcomes. Screening hallucination during the course of A.D. would be
      helpful. Further studies are needed to show the benefit of treatment of
      hallucination on the improvement of functional outcomes.

PMID- 15481077
TI  - Agreement between dementia patient report and proxy reports using the Nottingham
      Health Profile.
AB  - OBJECTIVE: The aim of the study was to examine the agreement between patient
      reports and their proxy reports (family and care provider proxies) on Health
      Status in a sample of patients with dementia. METHOD: Ninety-nine patients with
      mild to moderate dementia and proxies completed the 38-item Nottingham Health
      Profile (NHP) questionnaire. RESULTS: Completion rates for the different NHP
      dimensions ranged from 78 to 90% for the dementia subjects. Inter-rater agreement
      between different proxies and subject was from moderate to good for physical
      assessment (ICCs from 0.54 to 0.78 for physical mobility scales). Patient/family
      proxy concordance was moderate to good for five out of six dimensions (physical
      mobility, social isolation, pain, energy, sleep) and poor for emotional reaction.
      Family proxies systematically reported lower functioning than did patients in the
      four subscales assessing: physical mobility (p <0.0001), energy (p <0.005),
      social isolation (p <0.01) and sleep (p <0.03). Care provider proxies only
      estimated physical mobility as lower (p <0.0001). CONCLUSION: Age and physical
      status of the patient significantly affected agreement in patient-care provider
      proxy ratings. Thus, caution is appropriate when resorting to proxies to estimate
      the Health Status of a dementia patient.

PMID- 15481078
TI  - Radiographic assessment of resectability of locoregional disease in children with
      high-risk neuroblastoma during neoadjuvant chemotherapy.
AB  - BACKGROUND: The optimal timing for attempting removal of the primary tumor and
      regional disease in patients with high-risk neuroblastoma is uncertain. The
      purpose of this study was to evaluate resectability of the primary tumor and
      regional disease, as determined radiographically, in children with high-risk
      neuroblastoma during neoadjuvant chemotherapy. PROCEDURE: Patients enrolled in
      our institutional high-risk neuroblastoma protocol were evaluated prospectively
      by CT scan and/or MRI to determine the resectability of their primary tumor and
      regional disease at diagnosis, after two cycles of experimental therapy and after
      standard induction therapy. Tumors were considered to be unresectable if there
      was significant involvement with major vascular structures or contiguous organs,
      or would likely require nephrectomy to remove the entire tumor. RESULTS: Twenty
      four patients were referred prior to surgery for treatment of high-risk
      neuroblastoma. Seven of 24 (29%) patients were felt to be resectable at
      diagnosis, with an additional 9 patients becoming resectable after the initial
      experimental therapy. Thus, overall, 16 of 24 (67%) patients were felt to be
      resectable by the completion of the initial therapy. Only four additional
      patients of the remaining eight were considered resectable after the completion
      of standard induction therapy. CONCLUSIONS: Based on these data, we conclude that
      complete resection of the primary tumor and regional disease in children with
      high-risk neuroblastoma can be performed after an initial phase therapy in the
      majority of patients. Since earlier tumor removal may decrease the chance for the
      subsequent development of chemotherapy-resistant disease, we are recommending
      surgical resection as soon as the locoregional disease appears to be resectable.

PMID- 15481079
TI  - Can chest X-ray predict pneumonia severity?
AB  - Predictors of the severity of pneumonia have not been thoroughly evaluated among
      children in developed countries. We investigate whether chest radiographic
      findings could be used as predictors of severity of childhood pneumonia. The
      study included 167 children, aged more than 12 months, hospitalized in our
      department during a 4-year period with unilateral lobar or segmental pneumonia.
      The durations of fever and of hospitalization were considered indicators of
      severity of the disease. The size of the consolidation and its location in the
      left hemithorax were independently associated with severity of the disease.
      Univariate analysis showed that the mean duration of fever and of hospitalization
      as well as the prevalence of pleural effusion was significantly higher among
      children with left-sided pneumonia. A multiple logistic regression analysis
      revealed that only the presence of pleural effusion was significantly more likely
      in left-sided pneumonia (odds ratio, 2.65; 95% confidence interval, 1.09-6.47; P
      = 0.031). We conclude that the size of consolidation and the side of its location
      can be used as predictors of severity of pneumonia, with left-sided pneumonia
      running a more severe course, possibly due to increased risk for the development
      of pleurisy.

PMID- 15481080
TI  - Is routine chest radiography necessary for the initial evaluation of fever in
      neutropenic children with cancer?

PMID- 15481081
TI  - Megakaryopoiesis and thrombocytosis.

PMID- 15481082
TI  - Successful engraftment following unrelated donor transplant in an alloimmunized
      patient with Kostmann syndrome.
AB  - Severe chronic neutropenia (SCN) is characterized by severe recurrent bacterial
      infections during infancy. Blood or marrow transplantation (BMT) is the only
      curative option for patients with refractory disease. This report describes the
      case of a 4-year-old girl with refractory SCN, who received a bone marrow
      transplant from a highly matched donor after becoming HLA sensitized to multiple
      granulocyte transfusions. She is clinically well with normal blood counts and
      stable mixed chimerism 3 years after BMT. She experienced no graft rejection or
      graft versus host disease.

PMID- 15481083
TI  - Results of the implementation of liquid-based cytology-SurePath in the Ontario
      screening program.
AB  - BACKGROUND: The objective of the current study was to evaluate the adequacy and
      detection rates of SurePath after its implementation in Ontario. METHODS: The
      detection and adequacy rates of the SurePath liquid-based cytology system (SP
      LBC) were calculated for manually reviewed slides of the year 2002. The adequacy
      and detection rates from this study group were compared with a historical
      conventional smear (CS) group from the same laboratories during the same period
      of the previous year. RESULTS: The SP-LBC study group consisted of 352,680
      specimens with cytodiagnoses and the CS group included 378,990 specimens. The
      unsatisfactory rate for SP-LBC (0.24%) was less than that of the CS group
      (0.58%). The detection rate of atypical squamous cells (ASC+) by the SP-LBC group
      (4.69%) was greater than that of the CS group (3.81%), as was the detection rate
      of low-grade squamous intraepithelial lesions (LSIL+; 2.13% vs. 1.50% in the CS
      group). There was only a trend toward increased detection of high-grade squamous
      intraepithelial lesions (HSIL+) in the SP-LBC group (0.34%) relative to the CS
      group (0.31%), because the detection rate for carcinoma by SP-LBC declined.
      CONCLUSIONS: The implementation of SP-LBC has been followed by better specimen
      adequacy and detection rates for ASC+, LSIL+, and a trend of increased detection
      of HSIL+ relative to CS practice. To determine sensitivity rates, a
      histopathologic database for cervical carcinoma and precancer needs to be
      established.

PMID- 15481084
TI  - Ion activation methods for tandem mass spectrometry.
AB  - This tutorial presents the most common ion activation techniques employed in
      tandem mass spectrometry. In-source fragmentation and metastable ion
      decompositions, as well as the general theory of unimolecular dissociations of
      ions, are initially discussed. This is followed by tandem mass spectrometry,
      which implies that the activation of ions is distinct from the ionization step,
      and that the precursor and product ions are both characterized independently by
      their mass/charge ratios. In collision-induced dissociation (CID), activation of
      the selected ions occurs by collision(s) with neutral gas molecules in a
      collision cell. This experiment can be done at high (keV) collision energies,
      using tandem sector and time-of-flight instruments, or at low (eV range)
      energies, in tandem quadrupole and ion trapping instruments. It can be performed
      using either single or multiple collisions with a selected gas and each of these
      factors influences the distribution of internal energy that the activated ion
      will possess. While CID remains the most common ion activation technique employed
      in analytical laboratories today, several new methods have become increasingly
      useful for specific applications. More recent techniques are examined and their
      differences, advantages and disadvantages are described in comparison with CID.
      Collisional activation upon impact of precursor ions on solid surfaces, surface
      induced dissociation (SID), is gaining importance as an alternative to gas
      targets and has been implemented in several different types of mass
      spectrometers. Furthermore, unique fragmentation mechanisms of multiply-charged
      species can be studied by electron-capture dissociation (ECD). The ECD technique
      has been recognized as an efficient means to study non-covalent interactions and
      to gain sequence information in proteomics applications. Trapping instruments,
      such as quadrupole ion traps and Fourier transform ion cyclotron resonance
      instruments, are particularly useful for the photoactivation of ions,
      specifically for fragmentation of precursor ions by infrared multiphoton
      dissociation (IRMPD). IRMPD is a non-selective activation method and usually
      yields rich fragmentation spectra. Lastly, blackbody infrared radiative
      dissociation is presented with a focus on determining activation energies and
      other important parameters for the characterization of fragmentation pathways.
      The individual methods are presented so as to facilitate the understanding of
      each mechanism of activation and their particular advantages and representative
      applications.

PMID- 15481085
TI  - Anthracotic index and DNA methylation status of sputum contents can be used for
      identifying the population at risk of lung carcinoma.
AB  - BACKGROUND: Sputum cytology for the mass screening of lung carcinoma is a
      noninvasive, repeatable, and useful examination, but the detection rate is
      usually < 0.05% and the reliability is not high. METHODS: The anthracotic index
      (AI) and methylation status of the promoter regions of the p16, adenomatous
      polyposis coli (APC), and retinoic acid receptor-beta (RARbeta) genes were
      examined in 356 sputum specimens after routine cytologic examination. RESULTS:
      The mean AI of specimens from males was significantly higher than that from
      females. AI increased with increasing age and smoking index. The mean AI of
      patients with lung carcinoma was significantly higher than that of the
      nonaffected population. Furthermore, the mean AI of the specimens with or without
      cancer cells from patients with cancer was significantly higher than that of the
      nonaffected population. Abnormal methylation of the p16, APC, and RARbeta genes
      was detected in 21.7%, 28.2%, and 26.9% of specimens from patients with cancer,
      respectively. These ratios were significantly higher than those of the
      nonaffected populations (0%, 3.9%, and 7.6%, respectively). The incidences of
      abnormal methylation of the three genes were not associated with histologic
      classification, smoking index, gender, age, or occupation. CONCLUSIONS: These
      findings suggested that the AI and abnormal methylation status were useful for
      identifying a population at risk of lung carcinoma using mass screening of
      cytology specimens.

PMID- 15481086
TI  - Hydroxyapatite and titania sol-gel composite coatings on titanium for hard tissue
      implants; mechanical and in vitro biological performance.
AB  - Hydroxyapatite (HA) composites with titania (TiO2) up to 30 mol % were coated on
      a titanium (Ti) substrate by a sol-gel route, and the mechanical and biological
      properties of the coating systems were evaluated. Using polymeric precursors,
      highly stable HA and TiO2 sols were prepared prior to making composite sols and
      coatings. Coatings were produced under a controlled spinning and heat treatment
      process. Pure phases of HA and TiO2 were well developed on the composites after
      heat treatment above 450 degrees C. The HA-TiO2 composite coating layers were
      homogeneous and highly dense with a thickness of about 800-900 nm. The adhesion
      strength of the coating layers with respect to Ti substrate increased with
      increasing the TiO2 addition. The highest strength obtained was as high as 56
      MPa, with an improvement of about 50% when compared to pure HA (37 MPa). The
      osteoblast-like cells grew and spread actively on all the composite coatings. The
      proliferation and alkaline phosphatase (ALP) activity of the cells grown on the
      composite coatings were much higher than those on bare Ti, and even comparable to
      those on pure HA coating. Notably, the HA-20% TiO2 composite coating showed a
      significantly higher proliferation and ALP expression compared to bare Ti (p <
      0.05). These findings suggest that the sol-gel-derived HA-TiO2 composite coatings
      possess excellent properties for hard tissue applications from the mechanical and
      biological perspective.

PMID- 15481087
TI  - Modeling loop reorganization free energies of acetylcholinesterase: a comparison
      of explicit and implicit solvent models.
AB  - The treatment of hydration effects in protein dynamics simulations varies in
      model complexity and spans the range from the computationally intensive
      microscopic evaluation to simple dielectric screening of charge-charge
      interactions. This paper compares different solvent models applied to the problem
      of estimating the free-energy difference between two loop conformations in
      acetylcholinesterase. Molecular dynamics (MD) simulations were used to sample
      potential energy surfaces of the two basins with solvent treated by means of
      explicit and implicit methods. Implicit solvent methods studied include the
      generalized Born (GB) model, atomic solvation potential (ASP), and the distance
      dependent dieletric constant. By using the linear response approximation (LRA),
      the explicit solvent calculations determined a free-energy difference that is in
      excellent agreement with the experimental estimate, while rescoring the protein
      conformations with GB or the Poisson equation showed inconsistent and inferior
      results. While the approach of rescoring conformations from explicit water
      simulations with implicit solvent models is popular among many applications, it
      perturbs the energy landscape by changing the solvent contribution to microstates
      without conformational relaxation, thus leading to non-optimal solvation free
      energies. Calculations applying MD with a GB solvent model produced results of
      comparable accuracy as observed with LRA, yet the electrostatic free-energy terms
      were significantly different due to optimization on a potential energy surface
      favored by an implicit solvent reaction field. The simpler methods of ASP and the
      distance-dependent scaling of the dielectric constant both produced considerable
      distortions in the protein internal free-energy terms and are consequently
      unreliable.

PMID- 15481088
TI  - Poly (acrylic acid) chitosan interpolymer complexes for stomach controlled
      antibiotic delivery.
AB  - The aim of this study was to develop a stomach-specific drug delivery system to
      increase the efficacy of amoxicillin against Helicobacter pylori. Polyacrylic
      acid (PAA), chitosan (CS), and amoxicillin (A) were employed to obtain polyionic
      complexes. The design of the hydrogel delivery system was based on the swellable
      approach; with a floating feature to prolong the Gastric Residence Time (GRT).
      The polyionic complex (PAA:CS:A 2.5:5:2) showed a sustained drug release profile
      in enzyme-free simulated gastric fluid (SGF) and pH 4.0. A pH independent
      swelling-eroding pattern with adequate maximum swelling ratios of 17.76 and 13.42
      was obtained at in SGF and pH 4.0, respectively, with similar eroding profiles in
      both pH media. This network carrier provides an amoxicillin protective effect
      towards the hydrolytic degradation in SGF. The in vivo study was performed on
      healthy volunteers, using the [13C] octanoic acid breath test. The proposed
      hydrogel showed a prolonged GRT of up to 3 h. The preliminary results from this
      study suggest that amoxicillin polyionic complexes have potential for improving
      local antibiotic therapy against H. pylori.

PMID- 15481089
TI  - Ribonucleotide activation by enzyme ribonucleotide reductase: understanding the
      role of the enzyme.
AB  - This article focuses on the first step of the catalytic mechanism for the
      reduction of ribonucleotides catalyzed by the enzyme Ribonucleotide Reductase
      (RNR). This corresponds to the activation of the substrate. In this work a large
      model of the active site region involving 130 atoms was used instead of the
      minimal gas phase models used in previous works. The ONIOM method was employed to
      deal with such a large system. The results gave additional information, which
      previous small models could not provide, allowing a much clearer evaluation of
      the role of the enzyme in this step. Enzyme-substrate interaction energies,
      specific transition state stabilization, and substrate steric strain energies
      were obtained. It was concluded that the transition state is stabilized in 4.0
      kcal/mol by specific enzyme-substrate interactions. However, this stabilization
      is cancelled by the cost in conformational energy for the enzyme to adopt the
      transition state geometry; the overall result is that the enzyme machinery does
      not lead to a rate enhancement in this step. It was also found that the substrate
      binds to the active site with almost no steric strain, emphasizing the
      complementarity and specificity of the RNR active site for nucleotide binding.
      The main role of the enzyme at the very beginning of the catalytic cycle was
      concluded to be to impose stereospecifity upon substrate activation and to
      protect the enzyme radical from the solvent, rather than to be an reaction rate
      enhancement.

PMID- 15481090
TI  - Constant pH molecular dynamics in generalized Born implicit solvent.
AB  - A new method is proposed for constant pH molecular dynamics (MD), employing
      generalized Born (GB) electrostatics. Protonation states are modeled with
      different charge sets, and titrating residues sample a Boltzmann distribution of
      protonation states as the simulation progresses, using Monte Carlo sampling based
      on GB-derived energies. The method is applied to four different crystal
      structures of hen egg-white lysozyme (HEWL). pK(a) predictions derived from the
      simulations have root-mean-square (RMS) error of 0.82 relative to experimental
      values. Similarity of results between the four crystal structures shows the
      method to be independent of starting crystal structure; this is in contrast to
      most electrostatics-only models. A strong correlation between conformation and
      protonation state is noted and quantitatively analyzed, emphasizing the
      importance of sampling protonation states in conjunction with dynamics.

PMID- 15481091
TI  - Implementation and testing of stable, fast implicit solvation in molecular
      dynamics using the smooth-permittivity finite difference Poisson-Boltzmann
      method.
AB  - A fast stable finite difference Poisson-Boltzmann (FDPB) model for implicit
      solvation in molecular dynamics simulations was developed using the smooth
      permittivity FDPB method implemented in the OpenEye ZAP libraries. This was
      interfaced with two widely used molecular dynamics packages, AMBER and CHARMM.
      Using the CHARMM-ZAP software combination, the implicit solvent model was tested
      on eight proteins differing in size, structure, and cofactors: calmodulin,
      horseradish peroxidase (with and without substrate analogue bound), lipid carrier
      protein, flavodoxin, ubiquitin, cytochrome c, and a de novo designed 3-helix
      bundle. The stability and accuracy of the implicit solvent simulations was
      assessed by examining root-mean-squared deviations from crystal structure. This
      measure was compared with that of a standard explicit water solvent model. In
      addition we compared experimental and calculated NMR order parameters to obtain a
      residue level assessment of the accuracy of MD-ZAP for simulating dynamic
      quantities. Overall, the agreement of the implicit solvent model with experiment
      was as good as that of explicit water simulations. The implicit solvent method
      was up to eight times faster than the explicit water simulations, and
      approximately four times slower than a vacuum simulation (i.e., with no solvent
      treatment).

PMID- 15481092
TI  - Olfactory fossa of Tremacebus harringtoni (platyrrhini, early Miocene, Sacanana,
      Argentina): implications for activity pattern.
AB  - CT imaging was undertaken on the skull of approximately 20-Myr-old Miocene
      Tremacebus harringtoni. Here we report our observations on the relative size of
      the olfactory fossa and its implications for the behavior of Tremacebus. The
      endocranial surface of Tremacebus is incomplete, making precise estimate of brain
      size and olfactory fossa size imprecise. However, olfactory fossa breadth and
      maximum endocranial breadth measured from CT images of one catarrhine species and
      eight platyrrhine species for which volumes of the olfactory bulb and brain are
      known show that the osteological proxies give a reasonably accurate indication of
      relative olfactory bulb size. Nocturnal Aotus has the largest relative olfactory
      fossa breadth and the largest olfactory bulb volume compared to brain volume
      among extant anthropoids. Tremacebus had a much smaller olfactory fossa breadth
      and, by inference, bulb volume--within the range of our sample of diurnal
      anthropoids. Variations in the relative size of the olfactory bulbs in
      platyrrhines appear to relate to the importance of olfaction in daily behaviors.
      Aotus has the largest olfactory bulbs among platyrrhines and relies more on
      olfactory cues when foraging than Cebus, Callicebus, or Saguinus. As in other
      examples of nocturnal versus diurnal primates, nocturnality may have been the
      environmental factor that selected for this difference in Aotus, although
      communication and other behaviors are also likely to select for olfactory
      variation in diurnal anthropoids. Considering the olfactory fossa size of
      Tremacebus, olfactory ability of this Miocene monkey was probably not as
      sensitive as in Aotus and counts against the hypothesis that Tremacebus was
      nocturnal. This finding accords well with previous observations that the orbits
      of Tremacebus are not as large as nocturnal Aotus.

PMID- 15481093
TI  - Determination of impurities in pesticides and their degradation products formed
      during the wine-making process by solid-phase extraction and gas chromatography
      with detection by electron ionization mass spectrometry. II. Bromopropylate,
      trichlorphon, parathion-methyl and tebuconazole.
AB  - The presence of degradation products of bromopropylate, trichlorphon, parathion
      methyl and tebuconazole in white and red wines elaborated from musts spiked with
      commercial formulations of the pesticides was studied. Must and wine were
      subjected to solid-phase extraction followed by gas chromatography with electron
      ionization mass spectrometric detection. Alpha-bromophenylphenylmethanol,
      aminoparathion, acetylaminoparathion-oxon and dichlorvos have been identified as
      degradation products of bromopropylate, parathion-methyl and trichlorphon in
      wines, respectively. Moreover, the presence of additives and impurities of the
      formulations in elaborated wines has also been found.

PMID- 15481095
TI  - Utility of nonaqueous capillary electrophoresis for the determination of
      lidocaine and its metabolites in human plasma: a comparison of ultraviolet and
      mass spectrometric detection.
AB  - A nonaqueous capillary electrophoresis/electrospray mass spectrometry method for
      the separation of lidocaine (LID) and two of its metabolites,
      monoethylglycinexylidide (MEGX) and glycinexylidide (GX), has been developed. The
      separation medium was: 70 mM ammonium formate and 2.0 M formic acid in
      acetonitrile/methanol (60:40 v/v). With a sheath liquid of methanol/water (80:20
      v/v) containing 2% formic acid and positive ion detection, reproducible
      determinations (8-11% relative standard deviation (RSD)) of lidocaine and its
      metabolites were performed in spiked human plasma. The limits of detection (LODs)
      were between 69.1 and 337 nM. The influences of sheath liquid composition,
      nebulizing gas pressure and drying gas temperature on the separation were
      examined.

PMID- 15481096
TI  - Electrospray mass spectrometry studies of macromolecules containing 1,3
      oxazolidine moieties.
AB  - The polycondensation of terephthalaldehyde with 2-amino-2-methyl-1,3-propanediol
      using acidic catalysts leads to the formation of linear polymers and macrocyclic
      compounds with 2-(1',4'-phenylene)-5-methyl-1-aza-3,7-dioxabicyclo[3.3.0]octane
      as the repeating unit in all compounds. The structure of the polymer was
      determined by 1H- and 13C-NMR spectroscopy, and electrospray ionization mass
      spectrometric (ESI-MS) analysis. ESI-MS measurements were used to study the
      details of the polymer structure and support the equimolar alternating nature of
      bicyclo-O,N-acetals of terephthaldehyde in these macromolecules.

PMID- 15481097
TI  - Lobular neoplasia on core-needle biopsy--clinical significance.

PMID- 15481099
TI  - Use of unphased multilocus genotype data in indirect association studies.
AB  - It is usually assumed that detection of a disease susceptability gene via marker
      polymorphisms in linkage disequilibrium with it is facilitated by consideration
      of marker haplotypes. However, capture of the marker haplotype information
      requires resolution of gametic phase, and this must usually be inferred
      statistically. Recently, we questioned the value of the marker haplotype
      information, and suggested that certain analyses of multivariate marker data, not
      based on haplotypes explicitly and not requiring resolution of gametic phase, are
      often more powerful than analyses based on haplotypes. Here, we review this work
      and assess more carefully the situations in which our conclusions might apply. We
      also relate these analyses to alternative approaches to haplotype analysis,
      namely those based on haplotype similarity and those inspired by cladistics.

PMID- 15481098
TI  - Development of a compound-specific isotope analysis method for acetone via 2,4
      dinitrophenylhydrazine derivatization.
AB  - A novel method has been developed for compound-specific isotope analysis for
      acetone via DNPH (2,4-dinitrophenylhydrazine) derivatization together with
      combined gas chromatography/combustion/isotope ratio mass spectrometry
      (GC/C/IRMS). Acetone reagents were used to assess delta13C fractionation during
      the DNPH derivatization process. Reduplicate delta13C analyses were designed to
      evaluate the reproducibility of the derivatization, with an average error (1
      standard deviation) of 0.17 +/- 0.05 per thousand, and average analytical error
      of 0.28 +/- 0.09 per thousand. The derivatization process introduces no isotopic
      fractionation for acetone (the average difference between the predicted and
      analytical delta13C values was 0.09 +/- 0.20 per thousand, within the precision
      limits of the GC/C/IRMS measurements), which permits computation of the delta13C
      values for the original underivatized acetone through a mass balance equation.
      Together with further studies of the carbon isotopic effect during the
      atmospheric acetone-sampling procedure, it will be possible to use DNPH
      derivatization for carbon isotope analysis of atmospheric acetone.

PMID- 15481100
TI  - Quantitative determination of ochratoxin A in kidneys by liquid
      chromatography/mass spectrometry.
AB  - A sensitive liquid chromatography/electrospray ionization tandem mass
      spectrometry (LC/ESI-MS/MS) method for the quantitative determination of
      ochratoxin A (OTA) in kidney samples was developed. Ochratoxin B (OTB) was used
      as internal standard. Extraction of homogenized kidney samples was done by adding
      a chloroform/phosphoric acid mixture. Due to restriction of the sample size, less
      chloroform could be used than in previously described methods. Two different
      columns for clean-up were compared: strong anion exchange (Bond Elut SAX) and
      Extrelut NT columns. The high-performance liquid chromatography (HPLC) was used
      with gradient elution consisting of variable mixtures of formic acid (0.3%) in
      acetonitrile and formic acid (0.3%) in water. The mass spectrometer was operated
      in the positive ESI mode using multiple reaction monitoring. For OTA the
      precursor ion was m/z 404 while the product ions were at m/z 239 and m/z 341. For
      OTB the precursor ion was m/z 370 while the product ions were at m/z 205 and at
      m/z 324. A calibration curve of fortified kidney samples was used to quantify
      OTA. Method validation was performed according to Commission Decision
      2002/657/EC. Decision limit (CCalpha), detection capability (CCbeta), precision,
      bias, trueness, specificity and measurement uncertainty were determined. In
      general, the best results were obtained using SAX clean-up. CCalpha and CCbeta
      were 0.11 and 0.25 microg kg(-1), respectively. Within-laboratory reproducibility
      (% CV) was 9, 9, and 5% for OTA-fortified kidney samples of 0.5, 1, and 2.5
      microg kg(-1), respectively. Trueness (%) was 75, 69, and 57% for OTA-fortified
      kidney samples at 0.25, 0.5, and 1 microg kg(-1), respectively. Measurement
      uncertainty and expanded uncertainty were 14.85 and 29.70%, respectively. All
      criteria as laid down in Commission Decision 2002/657/EC were fulfilled.
      Therefore, this LC/ESI-MS/MS method can be used to monitor kidneys for OTA in the
      framework of Council Directive No. 96/23/EC.

PMID- 15481101
TI  - Continuous flow 2H/1H and 18O/16O analysis of water samples with dual inlet
      precision.
AB  - A method for isotope ratio analysis of water samples is described comprising an
      on-line high-temperature reduction technique in a helium carrier gas. Using a gas
      tight syringe, injection of 0.5 to 1 microL sample is made through a heated
      septum into a glassy carbon reactor at temperatures in excess of 1300 degrees C.
      More than 150 injections can be made per day and both isotope ratios of interest,
      delta2H and delta18O, can be measured with the same setup. The technique has the
      capability to transfer high-precision stable isotope ratio analysis of water
      samples from a specialized to a routine laboratory task compatible with other
      common techniques (automated injection for GC, LC, etc.). Experiments with an
      emphasis on the reactor design were made in two different laboratories using two
      different commercially available high-temperature elemental analyser (EA)
      systems. In the Jena TC/EA unit, sample-to-sample memory (single injection) has
      been reduced to approximately 1% and high precision of about 0.1 per thousand for
      delta18O and < 1 per thousand for delta2H has been achieved by a redesign of the
      glassy carbon reactor and by redirecting the gas flow of the commercial TC/EA
      unit. With the modified reactor, the contact of water vapour with surfaces other
      than glassy carbon is avoided completely. The carrier gas is introduced at the
      bottom of the reactor thereby flushing the outer tube compartment of the tube-in
      tube assembly before entering the active heart of the reactor.With the Leipzig
      high-temperature reactor (HTP) similar precision was obtained with a minor
      modification (electropolishing) of the injector metal sleeve. With this system,
      the temperature dependence of the reaction has been studied between 1100 and 1450
      degrees C. Complete yield and constant isotope ratio information has been
      observed only for temperatures above 1325 degrees C. For temperatures above 1300
      degrees C the reactor produces an increasing amount of CO background from
      reaction of glass carbon with the ceramic tube. This limits the usable
      temperature to a maximum of 1450 degrees C. Relevant gas permeation through the
      Al2O3 walls has not been detected up to 1600 degrees C.

PMID- 15481102
TI  - Fragmentation characteristics of permethylated oligosaccharides using a matrix
      assisted laser desorption/ionization two-stage time-of-flight (TOF/TOF) tandem
      mass spectrometer.
AB  - Matrix-assisted laser desorption/ionization two-stage time-of-flight (MALDI
      TOF/TOF) tandem mass spectrometry (MS/MS) was applied to characterize
      permethylated oligosaccharides. Under these ionization conditions such
      derivatives yield intense signals corresponding to sodium-cationized molecular
      species. A systematic study was conducted on a series of neutral and sialylated
      permethylated oligosaccharides to allow rationalization of the fragmentation
      processes. The major fragments observed in the MALDI-TOF/TOF-MS/MS spectra result
      from cleavage of glycosidic bonds, preferentially at N-acetylhexosamine and
      sialic acid residues. The fragments originating from both the reducing and the
      non-reducing ends of the glycan yield information on sequence and branching.
      Cross-ring cleavages, which are very informative of the linkages of the
      monosaccharide residues constituting these oligosaccharides, and 'internal'
      cleavage ions which are derived from elimination of substituents from around the
      pyranose ring, were also observed. This extensive fragmentation was shown to be
      useful for the structural characterization of oligosaccharides. MALDI-TOF/TOF
      MS/MS of permethylated oligosaccharides appears to be a powerful tool for
      carbohydrate structural analysis.

PMID- 15481103
TI  - Simultaneous localization of two linked disease susceptibility genes.
AB  - For diseases with complex genetic etiology, more than one susceptibility gene may
      exist in a single chromosomal region. Extending the work of Liang et al. ([2001]
      Hum. Hered. 51:64-78), we developed a method for simultaneous localization of two
      susceptibility genes in one region. We derived an expression for expected allele
      sharing of an affected sib pair (ASP) at each point across a chromosomal segment
      containing two susceptibility genes. Using generalized estimating equations
      (GEE), we developed an algorithm that uses marker identical-by-descent (IBD)
      sharing in affected sib pairs to simultaneously estimate the locations of the two
      genes and the mean IBD sharing in ASPs at these two disease loci. Confidence
      intervals for gene locations can be constructed based on large sample
      approximations. Application of the described methods to data from a genome scan
      for type 1 diabetes (Mein et al. [1998] Nat. Genet. 19:297-300) yielded estimates
      of two putative disease gene locations on chromosome 6, approximately 20 cM
      apart. Properties of the estimators, including bias, precision, and confidence
      interval coverage, were studied by simulation for a range of genetic models. The
      simulations demonstrated that the proposed method can improve disease gene
      localization and aid in resolving large peaks when two disease genes are present
      in one chromosomal region. Joint localization of two disease genes improves with
      increased excess allele sharing at the disease gene loci, increased distance
      between the disease genes, and increased number of affected sib pairs in the
      sample.

PMID- 15481104
TI  - Elisabeth Kubler-Ross.

PMID- 15481105
TI  - Should people with asymptomatic carotid artery stenosis undergo endarterectomy
      for primary stroke prevention?

PMID- 15481106
TI  - Substance dependence treatable, says neuroscience expert report.

PMID- 15481107
TI  - The Mannheim Declaration of Stroke in Eastern Europe. Accepted at the 13th
      European Stroke Conference, Mannheim-Heidelberg, Germany, May 12-15, 2004.

PMID- 15481108
TI  - Squamous cell carcinoma with sarcomatous stroma in the nasal cavity of a dog.
AB  - This is a report of an unusual squamous cell carcinoma in the nasal cavity of a
      dog. A 13-year-old Golden Retriever was presented with a unilateral nasal and
      ocular discharge. Although a nasal tumour was suspected, initial diagnostic
      investigations were unrewarding, and, with worsening clinical signs, the dog was
      euthanatized. Necropsy examination confirmed the presence of a nasal tumour that
      was composed histologically of both a well-differentiated squamous cell carcinoma
      component blending with a predominant spindle cell component. Immunohistochemical
      staining with anti-human keratin/cytokeratin (AE1/AE3, CAM 5.2 and broad spectrum
      cytokeratin), Vimentin, Desmin, smooth muscle actin and S-100 protein supported a
      diagnosis of a squamous cell carcinoma with (pseudo) sarcomatous stroma.

PMID- 15481110
TI  - Kaiser Foundation calls for stronger consumer protections in the new Medicaid
      drug benefit program.

PMID- 15481109
TI  - A novel Plasmodium falciparum ring stage protein, REX, is located in Maurer's
      clefts.
AB  - The asexual stages of the malaria parasite Plasmodium falciparum develop inside
      erythrocytes of the human host. Erythrocytes are highly specialized cells lacking
      organelles and trafficking machinery. The parasite must therefore establish its
      own transport system to export proteins and waste and import nutrients. A number
      of parasite-derived structures, implicated in trafficking, appear in the infected
      red blood cell at the late ring stage. We have identified a novel gene
      transcribed in ring stage parasites coding for a protein designated the ring
      exported protein, REX. REX is located in a red cell modification known as the
      Maurer's clefts, which are parasite induced structures implicated in trafficking
      of parasite proteins to the red blood cell surface. REX contains predicted coiled
      coil regions and a region with similarity to a domain in vesicle-tethering
      proteins. REX persists in Maurer's clefts throughout the infection of the
      erythrocyte, where it may play a role in the biogenesis and/or function of this
      organelle.

PMID- 15481111
TI  - The level playing field.

PMID- 15481112
TI  - Single-subject experiment evaluating nine different food sensitivity tests.

PMID- 15481113
TI  - Telemedicine: basic technical considerations.

PMID- 15481114
TI  - Abolishing the death penalty for juvenile offenders: a background paper.

PMID- 15481115
TI  - Executing juvenile offenders: a fundamental failure of society.

PMID- 15481116
TI  - Access to health care for adolescents and young adults.

PMID- 15481117
TI  - Future challenges in dentistry.

PMID- 15481118
TI  - What are the greatest problems that America's seniors face where oral health is
      concerned?

PMID- 15481119
TI  - Bibliography. Current world literature. Hearing science.

PMID- 15481120
TI  - Health and money in Afghanistan.

PMID- 15481121
TI  - Aiding the aiders.

PMID- 15481122
TI  - Tobacco is a "weapon of mass destruction". Should western countries be invaded
      for that?

PMID- 15481123
TI  - Confidential dilemma. Colo. hospital accused of using ethics rule as shield.

PMID- 15481124
TI  - Sharing stories: narrative medicine in an evidence-based world.

PMID- 15481125
TI  - Preoperative visits in anesthesia: communication patterns and sequences:
      application of an explorative analysis.

PMID- 15481126
TI  - "Doctor shoppers": at risk by any other name.

PMID- 15481127
TI  - Cryptosporidium reactive arthritis.

PMID- 15481128
TI  - Proceedings of the Meningococcal Vaccine Strategy World Health Organization
      satellite meeting, 10 March 2004, Auckland, New Zealand.
AB  - From 1991 to the end of 2003 there have been 5293 cases and 216 deaths from
      meningococcal disease in New Zealand. On 10 March 2004, the New Zealand Ministry
      of Health hosted a special meeting to release the first results of the clinical
      trial in 16 to 24 month olds of a new vaccine (MeNZB), which has been tailor-made
      to provide protection against the New Zealand epidemic strain. These proceedings
      summarise the key points from the meeting presentations and highlight some of the
      important issues considered in the subsequent discussion. In the toddler age
      group trial, 75% of the MeNZB recipients exhibited a four-fold or greater rise in
      serum bactericidal antibodies after three doses of MeNZB--compared with 4% of the
      control vaccine recipients. Local reactions to MeNZB and the control vaccine were
      common, especially injection site tenderness. These data, along with data from
      New Zealand clinical trials in four other age groups and efficacy and safety data
      from the Norwegian parent vaccine, were used to support the application for a
      licence to use MeNZB in a proposed mass immunisation programme for 0-19 year
      olds. During the immunisation programme, a comprehensive safety monitoring
      programme will be in place to monitor for any adverse reactions following MeNZB
      immunisation. This will include real-time hospital-based monitoring in the
      regions first to roll out the vaccine.

PMID- 15481131
TI  - [Epidemiologic study of SARS].

PMID- 15481130
TI  - [Progress in the study of animal hosts of hepatitis E].

PMID- 15481132
TI  - [Progress in the epidemiologic study of hemorrhagic fever with renal syndrome in
      China in recent years].

PMID- 15481133
TI  - [Epidemiologic study of cardiovascular diseases].

PMID- 15481134
TI  - [Progress in the epidemiologic study of variant Creutzfeldt-Jakob disease].

PMID- 15481135
TI  - CD14 is required for influenza A virus-induced cytokine and chemokine production.
AB  - Infection of monocytes and macrophages by influenza A virus leads to
      proinflammatory and chemotactic cytokine production. The signalling pathways
      linking innate immune virus recognition to cytokine expression are little
      understood. Here, we report that blocking of CD14 on human monocytes by specific
      antibody or use of CD14-deficient murine macrophages abolished influenza A virus
      induced cytokine production. Toll-like receptor (TLR) 2 and 4-deficient murine
      macrophages remained fully responsive. These results suggest that CD14, together
      with a TLR other than TLR2 or 4, is an essential coreceptor of the influenza A
      virus sensing recognition system.

PMID- 15481136
TI  - Transendothelial migration of CD16+ monocytes in response to fractalkine under
      constitutive and inflammatory conditions.
AB  - CD16+ monocytes represent 5-10% of circulating monocytes in healthy individuals
      and are dramatically expanded in several pathological conditions including AIDS
      and HIV-1-associated dementia (HAD). CD16+ monocytes constitutively produce high
      levels of pro-inflammatory cytokines and neurotoxic factors that may contribute
      to the pathogenesis of these disorders. Monocyte recruitment into the central
      nervous system (CNS) and other peripheral tissues in response to locally produced
      chemokines is a critical event in immune surveillance and inflammation and
      involves monocyte arrest onto vascular beds and subsequent diapedesis. Here we
      investigate the ability of CD16+ monocytes to undergo transendothelial migration
      (TEM) under constitutive and inflammatory conditions. CD16+ monocytes underwent
      TEM across unstimulated human umbilical vascular (HUVEC) and brain microvascular
      endothelial (BMVEC) cell monolayers in response to soluble fractalkine
      (FKN/CX3CL1). Stimulation with tumor necrosis factor (TNF) and interferon-gamma
      (IFN-gamma) induced high and low expression of membrane-bound FKN on HUVEC and
      BMVEC, respectively, together with expression of VCAM-1 and intercellular
      adhesion molecule-1 (ICAM)-1. By contrast, only HUVEC expressed CD62E while BMVEC
      remained negative. Both CD16- and CD16+ monocyte subsets adhered to TNF/IFN-gamma
      stimulated HUVEC with higher frequency than to unstimulated HUVEC. Monocyte
      chemoattractant protein-1 (MCP-1) triggered efficient TEM of CD16- monocytes
      across TNF/IFN-gamma-stimulated HUVEC, whereas soluble FKN failed to induce TEM
      of CD16+ monocytes across stimulated HUVEC. These results demonstrate that
      stimulation with TNF and IFN-gamma triggers expression of membrane-bound FKN on
      both HUVEC and BMVEC, but prevents TEM of CD16+ monocytes in response to soluble
      FKN. Thus, pro-inflammatory CD16+ monocytes may contribute to the pathogenesis of
      HAD and other inflammatory CNS diseases by affecting the integrity of the blood
      brain barrier as a consequence of their massive accumulation onto inflamed brain
      vascular endothelial cells expressing FKN and other adhesion molecules.

PMID- 15481137
TI  - Macrophage chemotaxis to apoptotic Burkitt's lymphoma cells in vitro: role of
      CD14 and CD36.
AB  - In Burkitt's lymphoma (BL), apoptosis occurs at high frequency alongside
      uncontrolled proliferation. Macrophages infiltrate these tumours in large numbers
      and engage in the phagocytic clearance of apoptotic cells in situ. Here we tested
      the hypothesis that apoptosis of BL cells may provide a mechanism for recruitment
      of macrophages to these tumours. We show that monocytes and macrophages, but not
      neutrophils, preferentially migrated to apoptotic BL cells in vitro. Transfection
      of BL cells with the anti-apoptotic gene bcl-2 both prevented apoptosis and
      abolished macrophage chemotaxis. Macrophage migration to BL populations
      correlated well with the number of apoptotic BL cells present (the Pearson
      correlation r = 0.81, p<0.0001). Chemoattraction of murine macrophages to
      apoptotic human BL cells demonstrated that the mechanism was conserved across
      these species. In an attempt to identify the macrophage receptors involved in
      this process, we investigated whether CD14 and CD36, two receptors important in
      the phagocytic clearance of apoptotic cells, were also involved in the
      chemotactic macrophage response. We found that bone marrow-derived macrophages
      from CD14-/- and CD36-/- mice moved as well as wild-type macrophages in
      chemotaxis assays towards apoptotic BL cells. Migrating macrophages were found to
      be up-regulated in their expression of CD14, however, suggesting that, although
      this receptor does not appear to be required for 'sensing' apoptotic cells, it
      may be up-regulated on the surface of the migrating macrophage in readiness for
      apoptotic corpse clearance.

PMID- 15481138
TI  - Lysophospholipid acyltransferases in monocyte inflammatory responses and sepsis.
AB  - Acyltransferases are important in the regulation of membrane phospholipid fatty
      acyl composition and together with phospholipase A2 enzymes control arachidonic
      acid incorporation and remodelling within phospholipids. In addition, monocyte
      and macrophage acyltransferase activity has been shown to respond to various
      inflammatory cytokines under conditions that can induce enhanced cellular
      responses. Work in our laboratory indicates that the enzyme
      lysophosphatidylcholine acyltransferase may mediate the priming reactions of
      monocytes to the cytokine interferon-gamma. Our recent studies suggest that this
      enzyme might also affect the responses of monocytes to the bacterial agent
      lipopolysaccharide that may be important in the development of sepsis. This
      article summarises the relationship between monocyte lysophosphatidylcholine
      acyltransferase, lipopolysaccharide and sepsis.

PMID- 15481139
TI  - The role of scavenger receptors in pathogen recognition and innate immunity.
AB  - Scavenger receptors represent a large family of structurally unrelated distinct
      gene products, expressed by myeloid and selected endothelial cells and able to
      recognise modified low-density lipoproteins. They also bind and internalise a
      variety of microbial pathogens, as well as modified or endogenous molecules
      derived from the host, and contribute to a range of physiological or pathological
      processes.

PMID- 15481140
TI  - The role of matrix metalloproteinase 7 in innate immunity.
AB  - Matrix metalloproteinase 7 (MMP-7), or matrilysin, is a secreted protease
      expressed by glandular and mucosal epithelial cells, keratinocytes, fibroblasts
      and macrophages. As with other MMPs it can act on the extracellular matrix and
      thereby regulate cell migration and tissue repair. In addition, MMP-7 has an
      important role in the maintenance of innate immunity in organs such as the lungs
      and intestines where it proteolytically activates anti-bacterial peptides such as
      pro-defensins. MMP-7 is also important for mediating proteolytic release of TNF
      from macrophages. Consistent with its role in innate immunity, MMP-7 is induced
      by microbial products and also, unexpectedly, by hypoxia.

PMID- 15481141
TI  - In vitro differentiation of porcine blood CD163- and CD163+ monocytes into
      functional dendritic cells.
AB  - Swine monocytes constitute a heterogeneous cell population containing subsets
      with distinct functional capacities or representing different maturational
      stages. Based on the expression of CD163, we have recently identified two
      monocyte subpopulations. In this study, we investigate the ability of both CD163-
      and CD163+ monocytes to differentiate into dendritic cells (DCs) in the presence
      of GM-CSF and IL-4. Monocyte differentiation into DC is accompanied by an up
      regulation of the expression of swine leukocyte antigen (SLA) I, SLA II and
      CD80/86 molecules, and a decrease in the expression of CD14, CD16 and CD163.
      These DC express the pan-myeloid marker SWC3 and display typical dendritic
      cytoplasmic projections. When monocytes are split into CD163+ and CD163- cells,
      both subsets give rise to DC. However, compared to CD163- monocyte-derived DC
      (MoDC), CD163+ MoDC appear to have reached a more advanced stage of maturation,
      expressing higher levels of SLA II and CD80/86 and inducing more efficiently
      proliferation of T cells to recall antigens and alloantigens.

PMID- 15481142
TI  - OM-197-MP-AC adjuvant properties: the in vitro maturation of normal and leukemic
      dendritic cells in a serum-free culture model.
AB  - Dendritic cells (DC) play a pivotal role in linking innate and adaptive immunity.
      Only mature DC are able to initiate adaptive immune responses by sensitising
      naive antigen-specific T cells. For clinical immunotherapeutic applications, safe
      and efficient clinical grade maturation factors of DC are required. Here, we
      investigated the impact of OM-197-MP-AC (OM-197), a synthetic lipid A analogue
      pseudo-dipeptide derived from amino acids linked to three fatty acid chains, on
      the maturation of human monocyte-derived-DC (Mo-DC) and leukemia-derived DC
      generated in serum-free conditions. After culture with clinical grade GM-CSF and
      IL-13, OM-197 at 20 microg/ml efficiently induced CD83+ Mo-DC. In comparison to
      immature Mo-DC that were derived by culture with GM-CSF and IL-13 only, CD40,
      CD80, CD86, HLA-ABC and HLA-DR molecules were up-regulated upon OM-197 or LPS
      treatment similarly. In MLR, OM-197-matured Mo-DC were found to be as potent
      stimulators as LPS-matured Mo-DC for CD4+ T cell proliferation. No significant
      difference in IFN-gamma quantification was shown between naive CD4+ T cells
      stimulated by LPS- or OM-197-Mo-DC suggesting that OM-197-Mo-DC can drive naive T
      cells towards a Th1 response profile that was mainly independent of IL-12
      secretion. Similarly, CD8+ T cells could be efficiently polarized into IFN-gamma
      secreting-cells by OM-197-Mo-DC, and activated polyclonal pp65-cytomegalovirus
      specific CD8+ T lymphocytes. Finally, myeloid leukemic blasts were able to
      differentiate in vitro into mature functional DC-like cells upon OM-197 treatment
      in our culture model. Overall, the in vitro effects of clinical grade adjuvant OM
      197, showed that it represents a potent inducer of both normal and leukemic-DC
      maturation, and is likely a good candidate for adjuvant immunotherapy in DC-based
      vaccines.

PMID- 15481143
TI  - IL-3 in dendritic cell development and function: a comparison with GM-CSF and IL
      4.
AB  - Dendritic cells (DC) develop in vivo from hematopoietic precursor cells. This
      process can be mimicked in vitro by growth factor stimulation. Among those
      factors granulocyte-macrophage colony-stimulating factor (GM-CSF) is the best
      known and most widely used for generation of rodent and human DC of the myeloid
      lineage. GM-CSF is often combined with interleukin-4 (IL-4) to suppress
      macrophage (Mph) outgrowth in cultures of human cells, but this does not apply to
      the mouse, and detailed analyses on the role of IL-4 are rare. Despite evidence
      for the importance of GM-CSF for DC development derived from in vitro data, GM
      CSF-deficient mice are largely normal with respect to their DC populations. This
      raised the interest in other growth factors for DC. IL-3 can also support DC
      growth in vitro, but has been neglected for some years. Now it has been revived
      by a series of publications. In this review, some new features of myeloid DC
      regarding their early developmental stages, the GM-CSF/IL-4-interplay, and the
      role of IL-3 are summarized.

PMID- 15481144
TI  - CNI-1493 mediated suppression of dendritic cell activation in vitro and in vivo.
AB  - The tetravalent guanylhydrazone CNI-1493 (CNI-1493) has been shown to inhibit
      macrophage activation, reduce systemic inflammation as well as proinflammatory
      cytokine production. Here we report for the first time that CNI-1493 also
      influences the biology of dendritic cells (DC). In order to become potent T cell
      stimulators of DC have to mature. Interestingly, when CNI-1493 was added to the
      maturation stimulus the expression of a typical DC-maturation marker i.e. CD83
      was reduced. Subsequent functional in vitro analyses showed that DC-mediated T
      cell stimulation was clearly reduced in CNI-1493-treated DC, underlining the
      functional impact that CNI-1493 on DC biology. Furthermore, the effect of CNI
      1493 was analyzed in vivo using the experimental autoimmune encephalomyelitis
      (EAE) model in C57BL/6 mice. Interestingly, in a prophylactic treatment regimen
      CNI-1493 prevented the paralysis associated with EAE almost completely. In
      addition, when applied in an early therapeutic setting CNI-1493 also reduced the
      clinical EAE symptoms. In summary, we show for the first time, that in addition
      to the earlier reported effects on macrophages, CNI-1493 also influences the
      function and biology of DC. Since DC are the only antigen-presenting cells (APC)
      known today to be able to prime naive T cells, the findings reported herein are
      highly relevant for the therapeutic application of CNI-1493.

PMID- 15481145
TI  - Immunomodulatory effects of the HIV-1 gp120 protein on antigen presenting cells:
      implications for AIDS pathogenesis.
AB  - Antigen presenting cell (APC) function is central to the development of an
      effective anti-viral immune response. Among APC, monocytes, macrophages and
      dendritic cells (DC) form the principal non-T cell compartment involved in in
      vivo HIV infection, and these cells play important and well-established roles in
      multiple aspects of viral pathogenesis. HIV infection may result in APC defects,
      which could ultimately contribute to the loss of CD4+ T cell responses observed
      early in HIV infection, when the CD4+ T cell number is still within the normal
      range. Extensive in vitro studies have demonstrated that the envelope
      glycoproteins of HIV-1 exert profound influences on various cell populations of
      the immune system, including hematopoietic progenitors, T and B lymphocytes,
      monocytes/ macrophages and DC, as well as on neuronal cells. The demonstration of
      the presence of envelope proteins both free in the circulation and bound to the
      surface of CD4+ cells suggests that gp120 interactions with non-infected cells
      can influence cellular functions in vivo, thus contributing to the
      immunopathogenesis of AIDS. This paper provides an overview of the present
      knowledge on gp120 binding, signal transduction triggering and interference with
      macrophage and DC functions and it highlights the importance of this interaction
      in the pathogenesis of AIDS.

PMID- 15481146
TI  - Identification of the mycobacterial carbohydrate structure that binds the C-type
      lectins DC-SIGN, L-SIGN and SIGNR1.
AB  - Mycobacterium tuberculosis represents a worldwide health risk and although
      macrophages are primarily infected, dendritic cells (DC) are important in
      inducing cellular immune responses against M. tuberculosis. Recent studies have
      demonstrated that M. tuberculosis targets the DC-specific C-type lectin DC-SIGN
      to inhibit the immuno-stimulatory function of DC through the interaction of the
      mycobacterial mannosylated lipoarabinomannan (ManLAM) to DC-SIGN, which prevents
      DC maturation and induces the immuno-suppressive cytokine IL-10. This may
      contribute to survival and persistence of M. tuberculosis. Here, we have
      identified the specific pathogen-derived carbohydrate structure on ManLAM that is
      recognized by DC-SIGN. We have synthesized the mannose-cap oligosaccharides man
      ara, (man)2-ara and (man)3-ara, and demonstrate that these neoglycoconjugates are
      specifically bound by DC-SIGN. Moreover, we demonstrate that the human and murine
      DC-SIGN homologue L-SIGN and SIGNR1, respectively, also interact with
      mycobacteria through ManLAM. Both homologues have the highest affinity for the
      (man)3-ara structure, similar to DC-SIGN. This study provides information about
      the specific carbohydrate structures on pathogens that are recognized by DC-SIGN,
      and may provide strategies to develop vaccines against these pathogens. Moreover,
      the identification of SIGNR1 as a receptor for ManLAM will enable in vivo studies
      to investigate the role of DC-SIGN in M. tuberculosis pathogenesis.

PMID- 15481147
TI  - The soluble form of CD83 dramatically changes the cytoskeleton of dendritic
      cells.
AB  - CD83 is the best-known surface marker for mature dendritic cells (DC) and
      recently we could show that a soluble form of CD83 inhibits DC maturation. In
      addition, this soluble form inhibits DC-mediated T cell proliferation in vitro
      and in vivo. Furthermore, several viruses induce CD83 degradation or shedding in
      infected DC. A soluble form of CD83 was also found in plasma and serum of healthy
      individuals and interestingly at highly elevated levels in a number of
      haematological malignancies. Thus, CD83 also has functional implications for the
      immune response. However, the molecular mechanism is not well defined. Here we
      describe for the first time that soluble CD83 completely changed the cytoskeleton
      (analysed using phalloidin-, tubulin- and fascin-specific antibodies) when
      administered at a concentration of 10 microg/ml to mature DC. The cells rounded
      off and had only short, truncated, or no veils at all. Furthermore, soluble CD83
      treated cells were completely inhibited in their ability to form clusters with T
      cells, an absolute prerequisite in order to stimulate T cells.

PMID- 15481148
TI  - C-Class CpG ODN: sequence requirements and characterization of immunostimulatory
      activities on mRNA level.
AB  - Synthetic oligodeoxynucleotides (ODN) containing unmethylated deoxycytosine
      deoxyguanosine (CpG) motifs are very potent inducers of the innate immune system,
      mimicking the effects of bacterial DNA. CpG ODN are recognized by Toll-like
      receptor 9 (TLR9). Three classes of TLR9 agonists have been described: B-Class
      CpG ODN that induce strong B- and NK-cell activation and A-Class ODN that induce
      very high levels of IFN-alpha by plasmacytoid dendritic cells. The recently
      described C-Class ODN combine most efficiently properties of A- and B-Class ODN
      in that they induce strong B-cell activation comparable to B-Class ODN together
      with IFN-alpha secretion comparable to A-Class ODN. Here, we investigate sequence
      requirements of C-Class ODN regarding optimal IFN-alpha secretion. Sequence as
      well as backbone modifications like 2'-O-methyl modifications especially in the
      5' part of the ODN influence IFN-alpha-producing capacity. Kinetic studies on
      mRNA level for CD69, IFN-gamma, IP-10 and IL-18 by semi-quantitative PCR
      demonstrated differences in mRNA transcription for some cytokines suggesting
      different regulatory mechanisms for different ODN classes. High amounts of IP-10
      mRNA and protein as well as up-regulation of IL-18 mRNA were observed especially
      for the A- and C-Classes. According to these data, C-Class ODN can be described
      as strong Th1 inducers with the stimulation of type I and II interferon as well
      as IP-10 production and strong NK activation. These characteristics can be
      availed to induce potent anti-tumor or anti-viral effects. Consequently, C-Class
      CpG ODN represent ideal drug candidates for anti-viral and/or anti-tumor therapy.

PMID- 15481149
TI  - Gene expression profiling of dendritic cells by DNA microarrays.
AB  - Dendritic cells (DC) are professional antigen presenting cells that play a
      pivotal role in initiating primary immune responses and have been implicated in
      determining the balance between immunity and tolerance. DC originate from
      hematopoietic stem cells in bone marrow and different DC subsets have been
      identified according to their phenotype, function, activation state and location.
      Gene expression analysis of DC by DNA microarrays represents a systemic approach
      to the underlying complexity of DC biology and is expected to provide important
      clues to the application of DC in the clinic. Here we review the recent findings
      from the use of DNA microarrays in DC biology and discuss the challenges emerging
      from these studies.

PMID- 15481151
TI  - Interaction of Leishmania parasites with dendritic cells and its functional
      consequences.
AB  - Interaction between dendritic cells (DC) and T cells is essential for the
      generation of cell mediated immunity and thus DC play a critical role in the
      initiation of immune responses against Leishmania parasites. Although macrophages
      (Mphi) are the major targets of all species of Leishmania, a number of studies
      demonstrated the infection of DC by Leishmania. DC specific intracellular
      adhesion molecule 3-grabbing nonintegrin (DC-SIGN), has been reported to be the
      receptor for Leishmania amastigotes. The functional consequences in DC after
      Leishmania infections appear to depend on species of Leishmania. Some species of
      Leishmania enhance the surface expression of co-stimulatory molecules and CD40
      ligand-induced IL-12 production in DC. On the other hand other species down
      regulate co-stimulatory molecules and inhibit IL-12 production. The intrinsic
      differences among Leishmania species with regard to alteration of cell surface
      molecules and IL-12 production in DC may contribute to the healing and non
      healing forms of the disease.

PMID- 15481150
TI  - Differential production of inflammatory chemokines by murine dendritic cell
      subsets.
AB  - Dendritic cells (DC) are efficient antigen presenting cells with the ability to
      activate naive T cells. Murine DC represent a heterogeneous population that can
      be subdivided into distinct subsets, including the conventional DC (cDC) which
      are either CD4(-)CD8(-) (DN), CD4(+)CD8(-) (CD4+) or CD4(-)CD8(+) (CD8+) subsets
      and the plasmacytoid DC (pDC), which have different immune regulatory functions.
      In this study, we investigated the differential expression of genes encoding the
      inflammatory chemokines Mip-1alpha, Mip-1beta and Rantes, and the secretion of
      these chemokines, among splenic DC subsets. These chemokine genes were expressed
      at higher levels by the splenic CD4+ and DN cDC subsets compared with the CD8+
      cDC, in both the resting and activated states in vivo. Both the pDC and cDC
      subsets displayed increases in chemokine secretion in response to a range of toll
      like receptor (TLR) stimuli in vitro. Whilst the pDC were the highest producers
      of Mip-1alpha and Mip-1beta in response to some TLR stimuli, the DN and CD4+ cDC
      subsets were the superior producers of Rantes. Overall, of the cDC, the CD4+ cDC
      produced all chemokines most efficiently, both at a basal level, and in response
      to most TLR stimuli. Thus, we report a new functional difference between the
      murine splenic cDC subsets, with the CD4+ cDC demonstrating the most efficient
      production of the inflammatory chemokines Mip-1alpha, Mip-1beta and Rantes.

PMID- 15481152
TI  - Signaling and immune regulatory role of the dendritic cell immunoreceptor (DCIR)
      family lectins: DCIR, DCAR, dectin-2 and BDCA-2.
AB  - This review focuses on a distinct family of dendritic cells (DC) expressing C
      type lectins that include DC immunoreceptor (DCIR), DC immunoactivating receptor
      (DCAR), DC-associated C-type lectin (dectin)-2 and blood DC antigen (BDCA)-2.
      DCIR is a type II C-type lectin expressed on antigen presenting cells and
      granulocytes and acts as an inhibitory receptor via an intracellular
      immunoreceptor tyrosine-based inhibitory motif (ITIM). In contrast, DCAR has been
      identified as a molecule that forms a putative pair with DCIR. While both
      molecules share the highly homologous extracellular lectin domain, DCAR lacks the
      ITIM in its short cytoplasmic tail and acts as an activating receptor through
      association with the Fc receptor gamma chain. Two other lectins, dectin-2 and
      BDCA-2, are highly related to DCAR by similarities of their amino acid sequence,
      molecular structure and chromosomal localization. Although they also lack the
      ITIM, they are capable of transducing signal to regulate cellular functions
      positively or negatively. Here we propose to designate these four highly related
      molecules as the "DCIR family lectins" and discuss their signaling mechanisms,
      carbohydrate recognition, and other features that contribute to the function of
      DC to control immunity.

PMID- 15481153
TI  - Heterogeneity of TLR-induced responses in dendritic cells: from innate to
      adaptive immunity.
AB  - Toll-like receptors (TLR) mediate recognition of several microbial products.
      Accumulating evidence indicates that TLR are capable of inducing distinct
      responses in dendritic cells and other antigen-presenting cells, and can direct T
      helper cell differentiation in opposing directions. The generation of such varied
      responses is achieved through the selective utilization of adaptor molecules that
      link TLR to distinct signal transduction pathways. The ability of TLR to activate
      and guide innate and adaptive immunity has the potential to be exploited for
      practical application that may lead to the development of more successful
      immunotherapies and vaccination strategies. A review of recent literature,
      unpublished observations, and future challenges is presented here.

PMID- 15481154
TI  - Expression of CD33-related siglecs on human mononuclear phagocytes, monocyte
      derived dendritic cells and plasmacytoid dendritic cells.
AB  - Siglecs are sialic acid binding Ig-like lectins mostly expressed in the
      haemopoietic and immune systems. Amongst the 11 human siglecs, there are eight
      proteins highly related to CD33 which have biochemical features of inhibitory
      receptors, containing two conserved tyrosine-based inhibitory motifs. Five of
      these (CD33/siglec-3, -5, -7, -9 and -10) are expressed on circulating monocytes.
      Here we show that monocytes cultured to differentiate into macrophages using
      either GM-CSF or M-CSF retained expression of these siglecs and their levels were
      unaffected following stimulation with LPS. In comparison, monocyte-derived
      dendritic cells down-modulated siglec-7 and -9 following maturation with LPS.
      Plasmacytoid dendritic cells in human blood expressed siglec-5 only. On
      monocytes, siglec-5 was shown to mediate rapid uptake of anti-siglec-5 (Fab)2
      fragments into early endosomes. This suggests, in addition to inhibitory
      signalling, a potential role in endocytosis for siglec-5 and the other CD33
      related siglecs. Our results show that siglecs are differentially expressed on
      mononuclear phagocytes and dendritic cells and that some can be modulated by
      stimuli that promote maturation and differentiation.

PMID- 15481155
TI  - Roles of lymphoid cells in the differentiation of Langerhans dendritic cells in
      mice.
AB  - Langerhans dendritic cells are antigen presenting cells (APC) that reside within
      the epidermis and are capable of stimulating naive T cells. Reciprocally,
      lymphocytes may play a role in Langerhans cells (LC) differentiation. Our results
      show that the differentiation of skin LC is unaffected in the absence of
      lymphocytes and/or signaling through the common cytokine receptor gamma chain
      (gammac) required for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 signaling.
      Migration of LC and other dendritic cells (DC) from the skin to the draining
      lymph nodes (LNs) after FITC skin sensitization, is unaffected in the absence of
      lymphocytes or CD40. FITC+ LC/DC sorted from the LNs of lymphoid deficient or
      control mice stimulated naive T cells with similar efficiency. However, while the
      absence of lymphocytes did not appear to affect the phenotype or number of
      emigrating LN DC/LC, their persistence in the LN appears to depend on alphabeta T
      cells. Thus, DC are strikingly reduced in numbers in the peripheral LNs of T-cell
      deficient mice. Finally, CD8alpha expression on skin emigrants was low and
      dependent on the presence of CD8+ lymphocytes, while spleen CD8+ DC were present
      in the absence of lymphocytes. We conclude that the presence of T cells is not
      required for the differentiation and migration of resident skin DC but is
      critical for the maintenance of DC and LC migrating into the LNs.

PMID- 15481156
TI  - The oligosaccharidic content of the glycoconjugates of the prepubertal descended
      and undescended testis: lectin histochemical study.
AB  - The saccharidic content of the glycoconjugates has been studied in the descended
      the undescended testes of a 8 years old boy. For this purpose, a battery of seven
      HRP-conjugated lectins (SBA, DBA,PNA,WGA,UEAI, LTA and ConA) was used. D
      galactose-N-acetyl-D-galactosamine and alpha-L-fucose sugar residues, which were
      present in the cytoplasm of the Sertoli cells of the normally positioned
      prepubertal testis, were not detected in the same cells of the undescended
      testis. The Leydig's cells of the descended testis appeared characterized by N
      acetyl-D-glucosamine which was absent in the rare and atrophic Leydig's cells of
      the cryptorchid testis. Differences in sugar residues distribution between the
      descended and the undescended testis were also detected in the lamina propria of
      the seminiferous tubules. Peritubular myoid cells in the undescended testis only
      reacted with PNA, after neuraminidase digestion, thus revealing the presence of D
      galactose (beta1-->3)-N-acetyl-D-galactosamine and sialic acid. In this study a
      complete distributional map of the sugar residues of the glycoconjugates in the
      descended and undescended prepubertal testis is reported.

PMID- 15481157
TI  - Lectin-binding sites in newborn human testis.
AB  - The present investigation has been performed to obtain a complete distributional
      map of the oligosaccharidic component of the glycoconjugates in the testis of the
      human newborn. For this purpose seven eight HRP-conjugated lectins (SBA, DBA,
      PNA, WGA, OOA, UEAI, LTA and ConA) along with enzymatic treatments, were used.
      The Sertoli cells were characterized by the same sugar residues detected in the
      testes of adult healthy subject. Beta-N-acetyl-D-galactosamine in the Leydig's
      cells and a-N- acetyl-D-galactosamine anomer in the spermatogonia seem to be an
      unique feature of the newborn testis. For this fact SBA and DBA could be
      considered markers respectively of the Leydig's cells and of the spermatogonia in
      the newborn testis. Differences in lectin binding, between the newborn and the
      adult testis as the interstitial tissue and the endothelial cells of the
      capillary vessels are reported.

PMID- 15481158
TI  - Smoking habit and labial microcirculation.
AB  - Smoking habit is an important risk factor in oral diseases. In the last years,
      many studies tried to evaluate smoking effects on the microcirculation. It had
      never been used such a simple not invasive technique, like the video
      capillaroscopic one. The aim of the research is to analyse "in vivo", the
      microcirculation labial characteristics, and to evaluate the smoking effects by
      means of computerised videocapillaroscopy techniques. 35 healthy no-smoker
      patients and 35 healthy smoker patients were examined. The characteristics of the
      microcirculation in the areas of labial mucous were examined using computerised
      videomicroscopic techniques. For each patient we evaluated the visibility, the
      course, the tortuosity and any images characteristic of capillary loops, besides
      the possible presence of microhaemorrhages, the average calibre of capillary
      loops and the number of capillary loops visible per square millimetre. The
      investigation was non invasive and repeatable for each patient. In both groups
      the investigation of labial mucous revealed a course of capillary loops parallel
      to the surface. In smoker patients, it was possible to underline capillaries of a
      smaller calibre (P<.001), and a higher number of detectable capillaries compared
      with no-smoker patients (P<.001). We observed an important correlation between
      the capillary tortuosity and the smoking habit (P<.001). Our research
      highlighted, that today it is possible to carry out a capillaroscopic
      investigation of labial mucous in a simple and reliable way. Furthermore, smoking
      habit represents a real risk factor of oral disease, greatly affecting the
      microcirculation.

PMID- 15481159
TI  - Phenotypic features of the domestic pigs bred in the Roman settlements of Pompeii
      and Caralis.
AB  - A reconstruction of the morphological features of domestic pigs from two Roman
      settlements is here suggested by means of the study of skeletal and dental
      remains, with the aim at evaluating their degree of selection in comparison with
      wild boars. Material was formed by 111 bone and tooth fragments and was uncovered
      during the excavations of Polybius' House in Pompeii and of Roman buildings in
      the neighbourhood of Caralis harbour (Sardinia). The remains underwent
      morphological examination. The eruption of permanent teeth and ossification of
      epiphyseal cartilages let us establish that most animals were over 18-20 months.
      When possible, the determination of sex was made by detecting tusk features. The
      presence of anthropic signs on the bone surface provides some information about
      slaughtering and cooking procedure in the Roman period and supports the
      hypothesis that the animal remnants were food remains. Osteometric analysis was
      carried out on long and short bones and teeth through suitable multiplicative
      parameters, leading to the assessment of the withers height and other main
      phenotypic features. Logarithmic deviation pointed out the significant
      osteometric differences between the domestic pigs from the two Roman settlements.
      These data were also compared with those from wild boars and modern crossbred
      wild boars X non-selected pigs. In conclusion, our data show that pigs from
      Caralis bear much resemblance to wild boars, whereas those from Pompeii appear to
      be improved, so sharing some phenotypic features of modem improved breeds.

PMID- 15481161
TI  - Criteria for deceit.

PMID- 15481160
TI  - Interferon-alpha affects the tumour necrosis factor-alpha content of mast cells
      in human nasal mucosa. A pilot study in allergic patients.
AB  - Human nasal mucosal mast cells contain and secrete tumour necrosis factor (TNF)
      alpha, which in turn can stimulate histamine secretion by these cells. Interferon
      (IFN)-alpha can inhibit TNF-alpha secretion by mast cells in vitro. We have
      addressed the interrelationships between IFN-alpha and the content in TNF-alpha
      and number of mast cells in vivo, in the human nasal mucosa. Biopsies were taken
      from two healthy control patients, two allergic patients and two more allergic
      patients treated topically with IFN-alpha for two weeks; biopsies from the last
      two patients were taken both before and after stimulation with the specific
      allergen. Mast cells were counted upon tagging with rhodaminated avidin and by
      indirect immunofluorescence for TNF-alpha. Data were subjected to analysis of
      variance. Mast cell numbers were significantly lower in all allergic patients
      than in controls (P<0.001). Upon IFN-alpha treatment, TNF-alpha positive mast
      cells were less than in allergic, untreated patients and the opposite was true
      for TNF-alpha negative mast cells (p<0.05). Allergen challenge caused selective,
      significant decrease only in the number of TNF-alpha negative mast cells
      (p<0.05). The results suggest that upon topical IFN-alpha treatment: (1) mast
      cells stores of TNF-alpha in the nasal mucosa of allergic patients are decreased;
      and (2) only TNF-alpha negative cells degranulate in response to allergen
      challenge. Therefore, one may expect that such a treatment reduces the TNF-alpha
      burden to the mucosa in these patients.

PMID- 15481162
TI  - Characteristics and proportion of dying Oregonians who personally consider
      physician-assisted suicide.

PMID- 15481163
TI  - Clarifying distinctions between contemplating and completing physician-assisted
      suicide.

PMID- 15481164
TI  - The role of the family in resolving bioethical dilemmas: clinical insights from a
      family systems perspective.

PMID- 15481165
TI  - Falling into line: the impact of utilization review hassles on physicians'
      adherence to insurance contracts.

PMID- 15481166
TI  - Chemical terrorism and the ethics of decontamination.

PMID- 15481167
TI  - Parents, lies, and videotape: covert video surveillance in pediatric care.

PMID- 15481168
TI  - Covert video surveillance in pediatric care: the fiduciary relationship with a
      child.

PMID- 15481169
TI  - Care and justice: the impact of gender and profession on ethical decision making
      in the healthcare arena.

PMID- 15481170
TI  - Culture and medical intervention.

PMID- 15481171
TI  - Use of videos by directors of medical ethics courses.

PMID- 15481172
TI  - Realising nurses' full potential.

PMID- 15481173
TI  - Nurses' communication must be considered in context.

PMID- 15481174
TI  - Nurses must maintain standards despite systems' problems.

PMID- 15481175
TI  - Primary health changes offer new opportunities for nurses.

PMID- 15481176
TI  - Primary health organisations on track to integrate services.

PMID- 15481177
TI  - Call for aged-care funding review welcomed.

PMID- 15481178
TI  - 'Just an ordinary nurse'. Interview by Anne Manchester.

PMID- 15481179
TI  - Relishing the challenges of rural nursing. Interview by Teresa O'Connor.

PMID- 15481180
TI  - Nursing in partnership with the community. Interview by Anne Manchester.

PMID- 15481181
TI  - Caring in an isolated community. Interview by Teresa O'Connor.

PMID- 15481182
TI  - What makes rural nursing different? Interview by Teresa O'Connor.

PMID- 15481183
TI  - Reducing children's hearing loss. Interview by Anne Manchester.

PMID- 15481184
TI  - Practice nurses feel undervalued.

PMID- 15481185
TI  - Embracing changes in primary health care.

PMID- 15481187
TI  - Is nursing's voice heard or heeded?

PMID- 15481186
TI  - Balancing work and life.

PMID- 15481188
TI  - Horizontal violence is 'insidious' in nursing education settings.

PMID- 15481189
TI  - Kai Tiaki pages reveal horizontal violence is not new in nursing.

PMID- 15481190
TI  - Health care assistants may undermine nursing in the future.

PMID- 15481191
TI  - Nurse practitioner role creates period of transition.

PMID- 15481192
TI  - University qualifications don't make better nurses.

PMID- 15481193
TI  - NZNO works hard to support enrolled nurses.

PMID- 15481194
TI  - The challenges of primary health care.

PMID- 15481195
TI  - Four pillars for primary health care nurses.

PMID- 15481196
TI  - Challenging primary health care nurses to take new action.

PMID- 15481197
TI  - Health gaps: who's to blame?

PMID- 15481198
TI  - How families experience mental health nursing care.

PMID- 15481199
TI  - Nurses must take their rightful place in mental health.

PMID- 15481200
TI  - Removing barriers between nurses and patients.

PMID- 15481201
TI  - Nurse practitioners must retain clinical focus.

PMID- 15481202
TI  - Older nurses face the challenges of tertiary study.

PMID- 15481203
TI  - NZNO moves to boost members in aged care.

PMID- 15481204
TI  - Varicella immunisation for staff and inmates of institutions: is this the next
      step in the UK?

PMID- 15481205
TI  - Fatal outbreak of chickenpox (varicella-zoster virus infection) among
      institutionalised adults with learning difficulties.
AB  - Most adults are not susceptible to chickenpox. We present a report of an outbreak
      of chickenpox among institutionalised adults with learning difficulties. An
      inventory of exposed and possible affected residents was done after three adult
      males were diagnosed with chickenpox following a case of zoster. Individuals with
      a recent history of chickenpox rash or herpes zoster were included as cases.
      Medical files were used to derive background information. Serum samples of the
      first two patients were tested for IgM varicella-zoster virus (VZV) antibodies.
      Eventually ten cases of chickenpox (eight residents and one group leader and her
      partner) and two residents with herpes zoster were registered over a period of
      four months in 2001. The first two patients tested positive in serum. One
      resident with chickenpox died. This outbreak suggests a higher risk from
      chickenpox for institutionalised adults with learning difficulties in comparison
      with the general Dutch population, probably due to limited contacts with the
      general population. Further research into varicella-zoster seroprevalence,
      preferably with low-invasive diagnostic methods, is necessary to determine if
      this potential risk is present elsewhere, since the risk of life-threatening
      chickenpox in adults could be reduced by the now available live attenuated VZV
      vaccine.

PMID- 15481206
TI  - Outbreak of chickenpox in a Scottish prison.
AB  - An outbreak of chickenpox occurred in a Scottish prison in April 2003. Three
      clinical cases (one virologically confirmed) were identified, two prisoners and
      one staff member. All were male and aged between 30 and 45 years. A further six
      possible cases were identified. The source of the outbreak was likely to have
      been a prisoner's child who visited the prison with a chickenpox rash. The
      outbreak was point source in nature, and no secondary spread of infection
      occurred within the prison despite the crowded conditions, possibly reflecting
      high levels of natural immunity. The outbreak serves as a reminder of the prison
      environment and the vulnerability of the prison population to infectious disease,
      both because of the prison environment and the clinical characteristics of the
      prison population.

PMID- 15481207
TI  - Delivering a selective neonatal BCG vaccination programme in a multi-ethnic
      community: an audit of the neonatal BCG immunisation programme in Birmingham and
      Solihull.
AB  - Neonatal bacillus Calmette-Guerin (BCG) immunisation is a primary preventive
      measure against tuberculosis. Local health professionals expressed concern about
      the variability of knowledge regarding eligible infants and uptake of the
      vaccine. A questionnaire was sent out to health visitors for use at the routine
      visit to babies. Details requested included ethnic group and country of origin of
      the infant, eligibility for BCG vaccination, and vaccination status. BCG
      vaccination was indicated for 41% of newborns. In total 74% of these eligible
      infants received the vaccine with a range of 36-83% between the five maternity
      units. There were inconsistencies within maternity units in identifying high-risk
      groups by ethnicity and country of origin, resulting in low coverage in certain
      eligible groups. Confusion exists about which infants are at risk of tuberculosis
      and should be vaccinated. Current national guidelines are not specific enough for
      cases of interracial parenting and for the increasingly diverse countries of
      origin of the population. In the absence of clearer national guidelines there is
      a need for pragmatic local guidance.

PMID- 15481208
TI  - Delay in reporting meningococcal disease to public health departments.
AB  - Prompt reporting of meningococcal disease improves the management of contacts. We
      looked at cases from five major local hospitals over a two-year period to
      ascertain the time taken to report and reasons for delays. Over 80% of cases were
      reported in the first 24 hours. Transfer to another unit was a frequent reason
      for a report being delayed. Nearly half the delayed cases were reported by the
      microbiology laboratory rather than the clinical team. We stress the need to
      emphasise timely reporting in the training of frontline medical staff, and the
      need to designate an individual in accident and emergency as responsible for
      reporting cases.

PMID- 15481209
TI  - Lessons from a pre-season influenza outbreak in a day school.
AB  - An outbreak of an upper respiratory tract illness at a secondary school, which
      led to the hospitalisation of 23 cases, occurred in Ireland at the beginning of
      September 2003. Medical and laboratory examinations, initially for suspected
      meningitis, were carried out on the hospitalised cases and bacterial meningitis
      was ruled out. One hundred and seventy-nine students and teachers were
      interviewed and a retrospective cohort study was conducted among the sixth year
      students. One hundred and seven respondents met the case definition, but no
      associations were found between the environmental exposures investigated and
      illness. As it was before the expected influenza season, initial samples were not
      tested for influenza, but one month later the new influenza A/Fujian/411/2002
      (H3N2)-like strain was confirmed and implicated in the outbreak. It was the first
      reported outbreak of influenza in Europe in the 2003 'winter' season and it
      demonstrated the need for vigilance for early and unexpected occurrence of
      influenza. It also provided valuable lessons for laboratory and epidemiological
      investigation and management of pre-season influenza.

PMID- 15481210
TI  - Microbiological quality of pre-cut fruit, sprouted seeds, and unpasteurised fruit
      and vegetable juices from retail and production premises in the UK, and the
      application of HAACP.
AB  - A study of ready-to-eat pre-cut fruit, sprouted seeds, and unpasteurised fruit
      and vegetable juices from retail and production premises was undertaken in the UK
      to determine the microbiological quality of these products, and to verify the
      application of hazard analysis and critical control points (HACCP) procedures by
      food operators. Almost all (99%; 2,075/2,096) samples were of
      satisfactory/acceptable microbiological quality. Two (0.1%) samples (melon,
      beansprouts) were of unacceptable quality due to the presence of Listeria
      monocytogenes at 102 cfu/g or more while a further 19 (0.9%) were unsatisfactory
      due to Escherichia coli levels in the range of 102 to 106 cfu/g. Neither
      Salmonella spp. nor E. coli O157 were detected in samples examined. A hazard
      analysis system was in place in most (85%) premises visited, and in 80% it was
      documented. Most managers (83%) had received some form of food hygiene training.
      Minimally processed produce is exposed to a range of conditions during production
      and distribution, and this may increase the potential for microbial
      contamination, highlighting the need of applying good hygiene practices from farm
      to fork to prevent contamination and/or bacterial growth. Such products should be
      stored and displayed at or below 8 degrees C.

PMID- 15481211
TI  - Enhancement of data collection from Welsh 'shopping basket' ready-to-eat food
      surveillance programme.
AB  - The method of data collection from the Welsh 'shopping basket' ready-to-eat food
      sampling programme has recently been reviewed, with the principal aim of reducing
      the resources required for inputting and audit of data. The subsequent
      improvements made have been primarily software based and they have made data
      collection, audit and analysis significantly faster and more efficient.

PMID- 15481212
TI  - Antimicrobial resistance and phage types of human and non-human Salmonella
      enterica isolates in Ireland, 1998-2003.
AB  - Between 1998 and 2003, 5,161 isolates (3,182 human) of Salmonella enterica were
      received by the National Salmonella Reference Laboratory of Ireland. Serotyping,
      antimicrobial susceptibility testing and phage typing were performed by standard
      methods. The number of isolates of S. enterica serovar Typhimurium decreased from
      579 (80%) in 1998 to 208 (19%) in 2003, while S. enterica serovar Enteritidis
      increased from 59 (8%) in 1998 to 219 (20%) in 2003. Definitive (DT) phage types
      104 and DT104b accounted for a declining proportion of all Salmonella Typhimurium
      isolates (from n = 523 [90%] in 1998 to 126 [60%] in 2003). Numbers of Salmonella
      Enteritidis phage type 4 declined from 50 (85%) in 1998 to 59 (27%) in 2003.
      Twenty-eight isolates of typhoidal Salmonella were received with a history of
      recent travel in 17 cases. Resistance to multiple (four or more) antimicrobial
      agents was related to serotype and, where applicable, phage type, and was common
      in Salmonella Typhimurium. Salmonella Typhimurium predominated among isolates
      from cattle and pigs (n = 213 [58%]), while Salmonella Livingstone (n = 327) and
      S. Kentucky (n = 227) were predominant in isolates from poultry (total n = 554
      [43%]). This paper discusses trends, and their implications, in Irish salmonella
      isolates since the establishment of the Reference Laboratory.

PMID- 15481213
TI  - In the shadow of HIV-HTLV infection in England and Wales, 1987-2001.
AB  - Like human immunodeficiency virus (HIV), human T-cell leukaemia/ lymphoma viruses
      (HTLV) I and II are persistent retroviral infections. Once infected, the lifetime
      risk of developing the HTLV-associated diseases, malignant or inflammatory, is
      low (approximately 5%). For those affected, however, these diseases are
      debilitating, with few treatment options and a poor prognosis. Surveillance of
      HTLV infections by the Communicable Disease Surveillance Centre (CDSC) has been
      ongoing since serological testing became available in 1986. Testing of blood
      donations in England and Wales commenced during August 2002 and awareness of HTLV
      infection is likely to increase. Therefore, a baseline retrospective review of
      cases prior to 2002 was conducted. The age and sex distribution of identified
      HTLV cases has differed little over time. Eighty-five per cent of individuals
      were linked to the Caribbean by birthplace or ethnicity. Though HTLV infection is
      chronic and incurable, preventive measures are possible. Improved surveillance is
      needed to support effective prevention activities.

PMID- 15481214
TI  - HTLV infection in England and Wales in 2002--results from an enhanced national
      surveillance system.
AB  - Human T-cell lymphotropic virus (HTLV) is a retrovirus transmitted through
      breastfeeding, sexual contact, blood transfusion and injecting drug use. HTLV is
      endemic in the Caribbean and parts of Africa, Japan and South America, with
      isolated foci in other areas. Infection is life-long. Less than 5% of those
      infected progress to one of the HTLV-related diseases, but these are debilitating
      and often fatal. Laboratory reports of new HTLV diagnoses are followed up through
      clinicians to establish information such as probable country of infection,
      country of birth, clinical details and reason for test. Clinician reports are
      also received for HTLV-infected blood donors identified by the National Blood
      Service. Seventy-seven individuals newly diagnosed with HTLV infection in 2002
      were reported to the Communicable Disease Surveillance Centre (CDSC) by June
      2003. Thirty-three (43%) were male, and 44 (57%) female, with median ages at
      diagnosis of 58.5 and 50.1 years respectively. Seventy-three (95%) individuals
      were HTLV-I positive and three HTLV-II positive, with one remaining untyped. For
      52 of the 77 infections, clinician reports were received. Where ethnicity was
      reported (48), 30 (63%) were Black Caribbean, 12 (25%) White, and the remainder
      (6) of other ethnicities. Probable route of infection was reported for 31
      individuals: nine (29%) were probably infected heterosexually, seven (23%)
      through mother-to-child transmission, 12 (40%) through either route, two through
      blood transfusion, and one through injecting drug use (HTLV-II positive). Where
      probable country of infection was reported (31), 14 (45%) were probably infected
      in the UK, 13 (42%) in the Caribbean, and four elsewhere. Where reported (50),
      reason for test was: symptoms for 19 (38%) individuals, blood donation for 21
      (42%), and the remainder for other reasons. Numbers of new HTLV diagnoses were
      relatively high in 2002, and the characteristics of patients and clinical
      presentations differed from previous years, mainly due to the introduction of
      blood donor testing for anti-HTLV. Beyond 2004, the number of HTLV-infected
      individuals detected through blood donation is expected to decline. While numbers
      of individuals affected are small compared to many other diseases, the infection
      is chronic and untreatable, and it is important that adequate standards of
      diagnosis, prevention, care and support are provided, and surveillance
      maintained.

PMID- 15481215
TI  - Monitoring the uptake of HIV testing among first attendees at GUM clinics in the
      East of England region.
AB  - This study was conducted to determine the extent to which genitourinary medicine
      clinics in the East of England region are monitoring the uptake of HIV testing.
      Ninety-four per cent of GUM clinics in the region offer HIV testing to all new
      patients. The uptake varied around the region, but all clinics are able to
      monitor uptake and the majority of clinics can audit uptake. The overall regional
      uptake has already exceeded the target for 2004.

PMID- 15481217
TI  - How should general practitioners investigate suspected urinary tract infection?
      Variations in laboratory-confirmed bacteriuria in South West England.
AB  - We analysed by age and sex the inter-laboratory variation in submission rates and
      positivity rates of urine samples from primary care that were submitted to seven
      microbiology laboratories within the South West of England. There was an almost
      twofold difference between the lowest and highest submission and positivity rates
      across all sex and age groups. This could not be accounted for by differences in
      population, age mix or numbers of nursing home beds. Increased submission in
      children will increase diagnosis of urinary tract infection (UTI). In contrast,
      over-investigation in other age groups increases laboratory and primary care
      costs and, in the asymptomatic elderly, may lead to unnecessary antibiotic
      treatment. Continued education is needed in primary care to improve the
      management of urinary symptoms. Laboratory-based studies of UTI are likely to
      underestimate the true incidence of this infection substantially. Standardised
      protocols for urine specimen submission are essential for practices and
      laboratories participating in surveillance of UTI and antibiotic resistance. In
      our discussion we offer seven recommendations for improving UTI investigation in
      general practice.

PMID- 15481216
TI  - Hepatitis B and hepatitis C seroprevalence and risk behaviour among community
      recruited drug injectors in North West Wales.
AB  - We estimated the prevalence of markers of hepatitis B virus (HBV) and hepatitis C
      virus (HCV) infection, and injecting risk behaviour, among community-recruited
      injecting drug users (IDUs) in North West Wales in 2001 and 2002. Sample
      collection was undertaken by trained current and former IDUs. Oral fluid samples
      (n = 153) were tested as part of the Unlinked Anonymous Prevalence Monitoring
      Programme ongoing survey of IDUs. Approximately 12% of the sample reported that
      they were currently in a drug treatment programme. Of the 153 samples screened
      27% (95% CI 20%-34%, 41/153) were anti-HBc positive, and 23% (95% CI 16%-30%,
      35/153) were anti-HCV positive. Sixteen per cent (95% CI 10%-22%, 25/ 153) of the
      samples were positive for both anti-HBc and anti-HCV. Of the subjects 15% (95% CI
      9%-20%) knew they had been vaccinated against hepatitis B. Direct sharing of
      needles and syringes in the 28 days prior to interview was reported by 44% (95%
      CI 35%-54%), and sharing of any equipment including that used for drug
      preparation prior to injection was reported by 66% (95% CI 57%-76%). In North
      West Wales, syringe sharing is a common practice, and a high proportion of IDUs
      have been exposed to bloodborne viruses. Hepatitis B vaccination coverage within
      this population appears to be low and needs to be increased. Further efforts are
      needed to improve the availability of clean injecting equipment.

PMID- 15481218
TI  - Is 10iu/L anti-HBs protective after hepatitis B vaccination?

PMID- 15481219
TI  - Shotgun sequencing the microbial diversity of the Earth.

PMID- 15481220
TI  - The challenge of CE marking.

PMID- 15481222
TI  - Sensitivity to Alzheimer's disease.

PMID- 15481221
TI  - Working alone.
AB  - Employees may be found working alone in a wide range of occupations.
      Technological advance, rationalisation and automation mean that more and more
      frequently. one single person is in charge of several machines, pieces of
      equipment or different work activities. Employees will be found working alone
      during work carried out as 'overtime', as part of flexible working hours, on
      Saturdays, Sundays, Bank Holidays and other statutory leave days, or in
      situations where their work takes them away from a fixed base (mobile workers). A
      person may be considered to be 'working alone' whenever it is not possible to
      offer immediate assistance following an accident or in another critical
      situation. This article looks at the legal background to lone working and what an
      employer must do to ensure lone workers are at no greater risk to their health
      and safety than any other members of the workforce.

PMID- 15481223
TI  - AOA presidential address to the 2004 congress.

PMID- 15481224
TI  - Change is the only constant variable.

PMID- 15481225
TI  - Rapid onset phacolysis.
AB  - BACKGROUND: Phacolysis involves the breakdown of a hypermature cataract, causing
      an antigenic reaction to the lens proteins released into the anterior chamber
      with subsequent inflammation. To date, the time it takes for a crystalline lens
      to reach hypermaturity and induce a phacolytic response has never been clearly
      detailed. It is believed that cataract maturation is a slow process. The process
      by which the lens proteins begin to leak is thought by many to be similarly slow.
      However, the immune-related inflammatory process that develops when the lens
      proteins begin to leak may be quite rapid. It may be an error to consider this
      aspect of the phacolytic process to be slow. METHODS: We present a case with a
      clear, timed delineation of the phacolytic process. A mature cataract became
      hypermature with subsequent phacolysis and inflammatory pressure rise over the
      course of 17 days. It appears that this is the first published account of the
      time involved in the development of phacolysis and, we believe, the fastest onset
      of the process. CONCLUSION: While cataract maturation is generally considered to
      be a slow, insidious process, it should be recognized that the phacolytic process
      might not be slow. Once a lens reaches hypermaturity, phacolysis could occur
      quite rapidly over the course of several days. This case could be an important
      consideration in management of the removal of advanced cataracts. This case may
      be the shortest reported time from diagnosis of a mature cataract to the
      development of inflammatory phacolysis and secondary glaucoma, occurring over a
      period of only 17 days.

PMID- 15481226
TI  - Retinal angiomatous proliferation: clinical characteristics and treatment
      options.
AB  - BACKGROUND: A new form of exudative age-related macular degeneration (ARMD),
      retinal angiomatous proliferation (RAP), has been described in which
      neovascularization begins in the deep retina, extends through the subretinal
      space, and eventually communicates with choroidal neovascularization. METHODS:
      Case series. RESULTS: Common clinical features of RAP include small multiple
      intra-retinal hemorrhages, intra-retinal edema, vascularized pigment epithelial
      detachments (PEDs), and retinal choroidal anastomosis (RCA). Fluorescein
      angiography (FA) reveals ill-defined, occult choroidal neovascularization.
      Indocyanine green (ICG) angiography is useful in early stages because 'hot spots'
      can be detected before clinical or FA characteristics are present. Optical
      coherence tomography (OCT) is useful in illustrating some of the clinical and FA
      characteristics. The use of photodynamic therapy (POT), combined with
      intravitreal triamcinolone injection, was successful in stabilizing the RAP
      lesion in one case discussed in this report. CONCLUSIONS: Retinal angiomatous
      proliferation is a newly recognized entity of exudative age-related macular
      degeneration with its own set of clinical, FA, ICG angiography, and OCT features.
      Experimental treatments such as the use of PDT combined with intravitreal
      triamcinolone injection demonstrate potential success with this entity. The
      biggest hope appears to be anti-angiogenic factors currently in clinical trials
      for the treatment of exudative ARMD.

PMID- 15481228
TI  - Community health center optometry.

PMID- 15481227
TI  - Silent sinus syndrome.
AB  - BACKGROUND: Silent sinus syndrome (SSS) is similar to and a subset of chronic
      maxillary atelectasis (CMA), which refers to a persistent decrease in sinus
      maxillary volume due to inward retraction of the maxillary sinus walls secondary
      to obstruction of the osteomeatal complex. It differs from CMA, however, in that
      there is no pain or maxillary sinus congestion. Patients with SSS usually
      manifest spontaneous unilateral enophthalmos and hypoglobus, with no history of
      facial trauma or surgery. They also do not have any nasal symptoms, sinusitis, or
      pain. CASE REPORT: A 28-year-old woman with asymptomatic enophthalmos and
      hypoglobus is described. The presentaton, diagnosis, and treatment of silent
      sinus syndrome are discussed. CONCLUSIONS: Silent sinus syndrome should be
      included in the differential diagnosis of enophthalmos and hypoglobus in the
      absence of trauma, surgery, and nasal symptoms. In addition to a thorough eye
      examination, axial and coronal computerized tomography of the sinus and orbits
      should be obtained to confirm the diagnosis.

PMID- 15481230
TI  - Our 'extended' staff.

PMID- 15481229
TI  - Patient referrals.

PMID- 15481231
TI  - Researchers make advances with bioengineered crown.

PMID- 15481232
TI  - Forensic dentistry: dentistry and bioterrorism.

PMID- 15481233
TI  - Identification by dental evidence: basics and beyond.
AB  - The use of dental information to identify unknown persons is an essential part of
      the response to a mass fatality incident. Moreover, the likelihood of future
      disasters due to terrorism, earthquakes and other causes requires the dental
      profession to prepare for an expanded role that would include bioterrorism
      response and emergency medical care. However, the profession's role in
      identification procedures will continue to be a major responsibility because it
      will still be a vitally important function, and it is within our area of
      expertise. This paper will provide a working understanding of the fundamentals of
      identification by dental evidence. It will also touch on some recent developments
      in this area.

PMID- 15481234
TI  - Lessons learned from the WTC disaster: a first-person account.
AB  - Sept. 11, 2001, was a day of learning for the world. We learned oceans do not
      isolate the United States from acts of terrorism. Prior to hijackers flying
      commercial airplanes into the Pentagon and World Trade Center towers, forensic
      investigators had never dealt with a mass fatality incident of this magnitude on
      the mainland soil of the U.S. during non-wartime conditions. During the process
      of gearing up for the task of locating and identifying the victims, forensic
      dentists also learned a number of things. Established techniques for disaster
      management were tested to their extreme limits. Before and while this multi
      functional effort was taking place, we familiarized ourselves with what
      techniques worked best under the immense pressure and tedious nature this job
      presented. Some of these accepted and now "tried and true" protocols are
      presented in this article.

PMID- 15481235
TI  - Mass fatality incidents: are California dentists ready to respond?
AB  - The role of dentists in identifying victims of mass disasters is well documented.
      The organization of dentists who are trained in identification procedures at a
      local, state, or federal level may be a valuable resource in the event of a mass
      disaster in California. This article explores the organization of dentists
      available to assist in a mass disaster at the state and federal level.

PMID- 15481236
TI  - Dental forensic identification in the 2003 Cedar Fire.
AB  - The Cedar Fire burned a large area of San Diego County in October 2003. By the
      time it was extinguished in mid-November, it had consumed more acres than any
      fire in California's history. Fifteen people lost their lives because of the
      fire. Forensic dentistry played a prominent role in the identification of the
      victims.

PMID- 15481237
TI  - Meeting a disaster's medical surge demand: can dentists help?
AB  - No one can deny that these are extraordinary times in world affairs. This is true
      not because there is turmoil in the world, which tends to be the norm, but
      because the problems in the world are dominated not by countries or religions,
      but by individuals and radical sects for whom life seems far too expendable. It
      is a time for each of us to determine how to respond to help protect our
      families. It is also a time for dentists to assess how they should respond to
      meet the additional demands placed upon them by way of their professional
      licenses and underlying responsibility to society. This article frames a set of
      commitments that the profession should consider assuming. It is related from the
      perspective of an institution that has taken an active role in societal
      protection from before Sept. 11, 2001, to the present. The discussion includes a
      description of the nature of medical surge demand and why the dental profession
      is uniquely positioned to assist in meeting this demand. The skill set of the
      dentist is highlighted in terms of triage ability, a role in bio-surveillance,
      the capacity to calm the "worried well," and community responsiveness. In
      addition, concepts like shelter in place and the Medical Reserve Corps are
      explained, and valuable reference sources and websites are provided.

PMID- 15481238
TI  - Dentists can contribute expertise in a major public health disaster.
AB  - BACKGROUND AND OVERVIEW: The time for dental professionals to educate themselves
      to respond to, and assist with, a catastrophic medical disaster is here.
      California dental healthcare workers must understand the various duties they may
      be asked to perform if a large-scale disaster were to occur. This article
      explores the various duties, which may need to be performed in the event of a
      medical disaster, and the duties a dentist, or dental auxiliary, may be able to
      complete, with minimal additional training. CONCLUSION: California dentists must
      be educated, at minimum, to recognize the symptoms of exposure to biological
      agents or naturally occurring diseases, such as avian flu and SARs, in their
      patients. Dentists must be further educated to correctly counsel their patients
      who exhibit such symptoms. Finally, dentists must alert the appropriate public
      health authorities of such exposure. California should consider amending the
      California Dental Practice Act to provide for the expansion of the definition of
      the practice of dentistry in the event of a declared healthcare emergency. The
      new definition should, at minimum, allow dentists to administer vaccines and
      dispense medications at a mass prophylactic distribution site. The definition
      could be further expanded to allow dentists to perform more complicated or
      invasive duties in the event of a disaster with large numbers of bodily injuries.
      In either event, California will also need to provide limited liability to
      dentists who do participate in emergency situations, similar to the Good
      Samaritan laws, which currently apply to physicians and surgeons. PRACTICE
      IMPLICATIONS: Dentists and their dental auxiliaries can augment the existing
      medical professionals, in responding to a declared medical emergency. In order to
      be ready to respond, dentists and their dental auxiliaries must receive
      additional training through continuing education courses developed specifically
      to train them in recognizing symptoms of exposure to biological agents.

PMID- 15481239
TI  - Fight, flight or bite.

PMID- 15481240
TI  - Determination of in vitro activity renin inhibitors by HPLC method.
AB  - A high-performance liquid chromatographic assay has been developed to the
      separation of angiotensin I, tetradecapeptide and the tetrapeptide Leu-Val-Tyr
      Ser. This purpose is achieved in a single step, using HPLC technique in the
      reversed phase system. The method is based on enzymatic hydrolysis of a substrate
      renin (TDP) with formation of angiotensin I (DP). After 1 h incubation at 37
      degrees C the reaction mixture is introduced directly into the chromatographic
      system. A 200 microl reaction mixture is needed for analysis. Acetonitrile
      gradient in 0.01 M ammonium acetate buffer allows a satisfactory separation of
      hydrolysis products. The application of this technique for the determination of
      in vitro renin activity and evaluation the potency of human renin inhibitors,
      employing the artificial renin substrate tetradecapeptide, is demonstrated.

PMID- 15481241
TI  - Spectrophotometric determination of Fe(II) and Zn(II) in the pharmaceutical
      multivitamin preparations with microelements.
AB  - 3-mercapto-5-(3,4-dihydroxyphenylazo-1')-1,2,4-triazole (METRIAP), 3-mercapto-5
      (2,4-dihydroxy-3-carboxyphenylazo-1)-1,2,4-triazole (METRIAREZ-gamma) and 2
      mercapto-5-(2,4-dihydroxy-5-carboxyphenylazol-)-1,3,4-thiadiazole (METIDAREZ
      beta), reagents synthesized in the Department of Medicinal Chemistry of Medical
      University in Lublin, have been used to determine Fe(II) and Zn(II) in Materna,
      Centrum, H-Pantoten pharmaceutical multivitamin preparations, containing other
      trace elements. Zn (II) with METRIAREZ-gamma at pH=7.35, and Fe(II) with METRIAP
      and METIDAREZ-beta at pH=10.30 or 7.40 constitute soluble in H2O colourful
      chelate compound at a mole ratio of 1:2 and 1:3, respectively. Volume stability
      constant of Fe(II) and Zn(II) complexes is equal to log K(METRIAP-Fe(II)) =
      16.46; log K(METRIAREZ-beta-Fe(II)) = 14.253; log K(METRIAREZ-gammaZn(II)) =
      11.47. Fe(III) and Zn(II) solutions were obtained by wet mineralisation of
      Materna, Centrum and H-Pantoten preparations with concentrated H2SO4 and 30% H2O2
      added. Spectrophotometric determination was carried out in an aqueous-methanolic
      solution environment. Statistically evaluated results were compared with the
      results of the AAS (atomic absorption spectrophotometry) determination method.
      Advantages of the Fe(II) and Zn(II) determination method are its precision RSD =
      0.23%-2.09% and repeatability as well as the possibility of Fe(II) determination
      without the necessity of masking or separating other trace elements.

PMID- 15481242
TI  - Determination of d-alpha-tocopherol and its impurity by chiral high performance
      liquid chromatography in pharmaceutical preparations.
AB  - In the present study we used chiral high performance liquid chromatography to
      determine d-alpha-tocopherol and its impurity in vitamin preparations. A
      chiralcel OD-H column was used for the chiral separation. Statistical evaluation
      of the results established a high accuracy and precision of this method.

PMID- 15481243
TI  - Preparation of floating pellets with verapamil hydrochloride.
AB  - The aim of this paper is to prepare a floating drug formulation in a gelatin
      capsule filled with tens of pellets with verapamil hydrochloride (VH) in a dose
      of 40 mg. The better solubility of VH in an acidic environment of the stomach may
      result in a greater amount of the drug absorbed. Pellets were prepared by wet
      granulation of a powder mixture, spheronization of the granulated mass and
      coating of the cores with aqueous dispersions of polymethylmethacrylate. Sodium
      hydrocarbonate contained in pellet cores ensures the flotation effect. Proper
      rate of VH release from pellets was obtained by a coating film of 25-105 microm
      thickness. Pellets of 1.25-1.6 mm size with a film of 75-85 microm thickness of
      considerably constant rate released the whole dose of VH in 6 h. During that time
      the pellets floated on the surface of the receptor solution.

PMID- 15481244
TI  - Isolation and identification of biologically active compounds from Forsythia
      viridissima flowers.
AB  - Flavonol glycosides, rutin and isoquercitrin, lignan glycosides, arctiin and
      matairesinoside, as well as phenylethanoid verbascoside (= acteoside), ursolic
      acid and beta-sitosterol have been isolated from the flowers of Forsythia
      viridissima. Two other isolated substances were characterized respectively as a
      wax and a hydrocoloidal polysaccharide consisting of galactose, galacturonic
      acid, arabinose, glucose, xylose, and rhamnose.

PMID- 15481245
TI  - Flavonoids from Metasequoia glyptostroboides.
AB  - From the autumnal leaves of Metasequoia glypstostroboides were isolated: 3'-O
      glucoside tricetin and ginkgetin, bilobetin, 2,3-dihydroisoginkgetin--new
      compounds in this plant.

PMID- 15481246
TI  - Polyphenolic compounds from Platycodon grandiflorum A. DC.
AB  - Flavonoids and phenolic acids from the aerial parts of Platycodon grandiflorum A.
      DC. were analysed by isocratic TLC, MGD-TLC and HPLC methods. Four flavonoid
      compounds were determined including luteolin 7-O-glucoside as the main component
      and apigenin 7-O-glucoside, luteolin and apigenin. When performing HPLC analysis,
      12 phenolic acids in the free, depside and glycoside forms were identified. Among
      them, 3,4-dimethoxycinnamic, caffeic, chlorogenic, ferulic, isoferulic,
      homovanillic, alpha-resorcylic, m-coumaric, p-coumaric, p-hydroxybenzoic, 2
      hydroxy-4-methoxybenzoic and 2,3-dihydroxybenzoic acids.

PMID- 15481247
TI  - Influence of felbamate on selected central effects of ethanol in experimental
      animals.
AB  - Both felbamate and ethanol demonstrate complex action on central nervous system
      (CNS). There are several data indicating that ethanol influences pharmacokinetics
      of new generation of antiepileptic drugs. Investigation of CNS interaction of
      felbamate and ethanol may bring up some suggestions as for adverse reactions of
      concomitance of these substances and consequences of such reactions are
      concerned. The influence of felbamate on the action of ethanol in a rota-rod test
      (1.5 g/kg), the duration of ethanol sleeping time (4 g/kg) as well as on
      spontaneous locomotor activity (2 g/kg) and ethanol-induced hypothermia (2.5
      g/kg) was investigated. Felbamate was administered at a single dose (200 mg/kg
      i.p.) or as daily injections dose (50 mg/kg for 10 days). At a single dose,
      felbamate prolonged ethanol-sleeping time, increased ethanol-induced disturbances
      of motor coordination and ethanol-induced hypothermia as well as prevented
      increased locomotor activity observed after ethanol intake. Felbamate
      administered for 10 days reduced ethanol sleeping time, did not effect ethanol on
      locomotor activity of mice, but augmented ethanol-induced changes in motor
      coordination and ethanol hypothermia. These interactions may be of
      pharmacodynamic character, but pharmacokinetic nature cannot be excluded,
      felbamate and ethanol are substrates for the cytochrome CYP2E1.

PMID- 15481248
TI  - Synthesis, structure and pharmacology of acyl-2,6-xylidines.
AB  - L-2-perhydroheterocyclicalkyl acids were condensed with 2,6-xylidine. 8 new
      optically active acyl-2,6-xylidines were obtained. Absolute configuration of acyl
      2,6-xylidines were selected for pharmacological examinations.

PMID- 15481249
TI  - New nucleoside analogs in the treatment of hematological disorders.
AB  - Cytotoxic nucleoside analogs have a broad clinical use. They were among the first
      chemotherapeutic agents used in the treatment of malignant diseases. The
      anticancer nucleosides include analogs of physiologic pyrimidine and purine
      nucleosides. They are used in oncology in the treatment of both, solid tumors and
      hematological malignancies. These agents have many intracellular targets, e.g.
      they act as antimetabolites, competing with natural nucleosides during DNA or RNA
      synthesis and as inhibitors of key cell enzymes. Understanding of the mechanisms
      of action of these compounds and synthesis of new analogs provides the
      possibility to further expand the spectrum of their clinical use and enhance
      their antitumor activity. In this paper we describe mechanisms of action and
      possible clinical use in the treatment of hematological malignancies of these
      nucleoside analogs, which are now in different stages of clinical trials, namely
      tezacitabine, troxacitabine, clofarabine, nelarabine, decitabine, CNDAC and ECyD.

PMID- 15481250
TI  - Polycyclic aromatic hydrocarbons: physicochemical properties, environmental
      appearance and impact on living organisms.
AB  - Human exposure to environmental pollution is of great interest nowadays. Many
      substances present in the environment are considered as carcinogenic to humans.
      Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental carcinogens.
      In this paper, PAHs are described: their physicochemical properties, natural and
      anthropogenic sources, environmental, dietary and occupational exposure and
      impact on human health. Metabolical carcinogenic activation of PAHs and the role
      of metabolism products as biomarkers of PAH exposure have been discussed.

PMID- 15481251
TI  - Optimisation of the derivatisation reaction and subsequent headspace solid-phase
      microextraction method for the direct determination of chlorophenols in red wine.
AB  - An acetylation reaction for the derivatisation of the three chlorophenols
      involved in cork taint was optimised using a Doehlert design for direct
      application in wine samples. In this first step, the optimum reaction pH, by
      adding different amounts of KHCO3, and the required quantity of derivatisation
      reagent were fixed. Then a series of parameters relevant for the headspace solid
      phase microextraction process, such as desorption conditions, salt addition and
      agitation sample were evaluated. A simultaneous study of the type of fibre and
      extraction temperature was performed at five levels and based on the results
      obtained the rest of factors (sample volume and exposition time) that could
      potentially affect the extraction yields were optimised by a central composite
      design. According to the validation of the method, we propose here, to our
      knowledge, the first application of solid-phase microextraction for the direct
      analysis of chlorophenols in red wine samples.

PMID- 15481252
TI  - Supercritical fluid extraction for pesticide multiresidue analysis in honey:
      determination by gas chromatography with electron-capture and mass spectrometry
      detection.
AB  - An analytical procedure using supercritical fluid extraction (SFE) and capillary
      gas chromatography with electron-capture detection was developed to determine
      simultaneously residues of different pesticides (organochlorine,
      organophosphorus, organonitrogen and pyrethroid) in honey samples. Fortification
      experiments were conducted to test conventional extraction (liquid-liquid) and
      optimize the extraction procedure in SFE by varying the CO2-modifier,
      temperature, extraction time and pressure. Best efficiency was achieved at 400
      bar using acetonitrile as modifier at 90 degrees C. For the clean-up step,
      Florisil cartridges were used for both methods LLE and SFE. Recoveries for
      majority of pesticides from fortified samples of honey at fortification level of
      0.01-0.10 mg/kg ranged 75-94% from both methods. Limits of detection found were
      less than 0.01 mg/kg for ECD and confirmation of pesticide identity was performed
      by gas chromatography-mass spectrometry in selected-ion monitoring mode. The
      multiresidue methods in real honey samples were applied and the results of
      developed methods were compared.

PMID- 15481253
TI  - Effect of hindered diffusion on the adsorption of proteins in agarose gel using a
      pore model.
AB  - The hindered diffusion and binding of proteins of different sizes (lysozyme, BSA
      and IgG) in an agarose gel is described using adsorption kinetic and diffusional
      data together with an experimentally determined pore size distribution in the
      gel. The validity of the pore model, including variable diffusion coefficients
      and porosities is tested against experimental confocal microscopy data. No
      fitting parameters were used in the present model. The importance of knowing the
      gel structure is demonstrated especially for large proteins such as IgG.
      Experimental confocal microscopy data can be explained by the present model.

PMID- 15481254
TI  - Continuous desorption rate measurement from a shallow-bed of poly(styrene
      divinylbenzene) particles with correction for experimental artifacts.
AB  - A 0.50 mm high bed, containing ca. 3 mg of the nominally non-porous poly(styrene
      divinylbenzene) (PS-DVB) sorbent Hamilton PRP-infinity, is located in a valve.
      After the bed is pre-equilibrated with a (7/3) methanol/water solution of
      naphthalene (NA), the valve is switched and (7/3) methanol/water solvent flows
      continuously through the bed at a high linear velocity. This causes NA to desorb
      into a constantly refreshed solvent, creating a "shallow-bed" contactor with an
      "infinite bath" kinetic condition. The effluent from the bed passes through a UV
      absorbance detector which generates the observed instantaneous desorption rate
      curve for NA. The same experiment is performed using the solute phloroglucinol
      (PG), which is not sorbed by PRP-infinity and serves as an "impulse response
      function marker" (IRF-Marker). The resulting peak-shaped IRF curve is used in two
      ways (i.e. subtraction and deconvolution) in order to correct the observed
      instantaneous rate curve of NA for the following experimental artifacts: hold-up
      volume of the bed and valve, transit-delay time between the bed and the detector
      and instrument bandbroadening of the NA zone. The cumulative desorption rate
      curve, which is a plot of moles NA desorbed versus time, is obtained by
      integration. It is found to be accurately described by the theoretical equation
      for homogeneous spherical diffusion. The diffusion coefficient of NA inside the
      PRP-infinity particles (5.0+/-0.6) x 10(-11) cm2/s, agrees with the literature
      value that was obtained from the sorption rate of NA into the same particles.
      This constitutes virtually conclusive evidence for diffusion control of intra
      particle kinetics of NA in the PS-DVB matrix of PRP-infinity and related
      polymers. The influence of both sorbent and solute properties on the method is
      evaluated.

PMID- 15481255
TI  - Effect of mobile phase composition, pH and buffer type on the retention of
      ionizable compounds in reversed-phase liquid chromatography: application to
      method development.
AB  - Optimizing separation of ionizable compounds in order to find robust conditions
      has become an important part of method development in liquid chromatography. This
      work is an attempt to explain the observed variations of retention of acid and
      basic compounds with the organic modifier content in the mobile phase, according
      to various factors: the type of modifier, the type of buffer, the temperature and
      of course the type of solute. This is done by considering the variation of the so
      called chromatographic pKa which refers to the pH measured in the aqueous medium
      and is determined from retention data. A procedure is described that accurately
      relates, from nine experiments, retention to solvent composition and pH. The
      limits of such a procedure are evaluated and two examples of optimized
      separations of basic compounds are given.

PMID- 15481256
TI  - Simple reversed-phase liquid chromatography method for determination of
      tocopherols in edible plant oils.
AB  - A simple and rapid reversed-phase high-performance liquid chromatography method
      for determination of alpha-, (beta + gamma), and delta-tocopherols in edible
      plant oils has been developed. Oils are diluted in 2-propanol and injected
      directly onto Symmetry C18 column. Methanol and acetonitrile (1:1) are used as a
      mobile phase. Tocopherols are detected using fluorescence detector set at
      excitation and emission wavelength 295 nm and 325 nm, respectively. The method is
      precise (R.S.D. not higher than 2.24%) and sensitive-detection limits (DL) are 8
      ng/ml for gamma- and delta-tocopherols and 28 ng/ml for alpha-tocopherol;
      quantification limits (QL) were calculated as three times higher than DL.

PMID- 15481257
TI  - Monitoring multi-class pesticide residues in fresh fruits and vegetables by
      liquid chromatography with tandem mass spectrometry.
AB  - A new analytical method was developed using liquid chromatography with tandem
      mass spectrometry for the routine analysis of 31 multi-class pesticide residues
      and applied to approximately 50 fresh fruit and vegetable samples (green bean,
      cucumber, pepper, tomato, eggplant, watermelon, melon and zucchini). Extraction
      of the pesticides with ethyl acetate was carried out. The optimal ionisation
      conditions were selected for each pesticide in the same run. The procedure was
      validated and the values of some merit figures, such as recovery, precision,
      linear range, detection limit and quantification limit for each pesticide were
      calculated together with its calculated expanded uncertainty (U). The average
      recoveries in cucumber obtained for each pesticide ranged between 74 and 105% at
      two different fortification levels (n = 10 each) that ranged between 9 and 250 ng
      g(-1) (depending on the pesticide). The uncertainty associated to the analytical
      method was lower than 23% for all compounds tested. The calculated limits of
      detection and quantitation were typically <1 ng g(-1) that were much lower than
      the maximum residue levels established by European legislation.

PMID- 15481258
TI  - High-performance liquid chromatographic analysis of dextromethorphan, guaifenesin
      and benzoate in a cough syrup for stability testing.
AB  - A method has been developed for the analysis of a cough syrup containing
      dextromethorphan, guaifenesin, benzoic acid, saccharin and other components.
      Forced degradation was also studied to demonstrate that the method could be
      employed during a stability study of the syrup. Final conditions were phosphate
      buffer (25 mM, pH 2.8) with triethylamine (TEA)-acetonitrile (75:25, v/v). In
      such conditions, all the actives, excipients and degradation products were
      baseline resolved in less than 14 min, and different wavelengths were used for
      the different analytes and related compounds.

PMID- 15481259
TI  - Determination of explosives in environmental water samples by solid-phase
      microextraction-liquid chromatography.
AB  - When explosives are present in natural aqueous media, their concentration is
      usually limited to trace levels. A preconcentration step able to remove matrix
      interferences and to enhance sensitivity is therefore necessary. In the present
      study, we evaluated solid-phase microextraction (SPME) technique for the recovery
      of nine explosives from aqueous samples using high-performance liquid
      chromatography with ultraviolet detection (HPLC-UV). Several parameters,
      including adsorption and desorption time, coating type, rate of stirring, salt
      addition, and pH, were optimized to obtain reproducible data with good accuracy.
      Carbowax coating was the only adsorbent found capable of adsorbing all explosives
      including nitramines. Method detection limits (MDL) were found to range from 1 to
      10 microg/L, depending on the analyte. SPME/HPLC-UV coupling was then applied to
      the analysis of natural ocean and groundwater samples and compared to
      conventional solid-phase extraction (SPE/HPLC-UV). Excellent agreement was
      observed between both techniques, but with an analysis time around five times
      shorter, SPME/HPLC-UV was considered to be applicable for quantitative analysis
      of explosives.

PMID- 15481260
TI  - Sensitivity of the methylbenzenes and chlorobenzenes retention index to column
      temperature, stationary phase polarity, and-number and chemical nature of
      substituents.
AB  - Retention indices of methylbenzenes and chlorobenzenes on two fused silica
      capillary columns, HP-5 (diphenylsiloxane 5% diphenyldimethylsiloxane) and ZB-WAX
      (polyethylene glycol), have been calculated at various isothermal temperatures
      and compared with literature data. The retention index temperature effect was
      studied for each solute, finding greater retention index the higher the column
      temperature. A comparison between the straight line fit and the fit to the
      recently proposed equation I = A + B/T +C ln T was carried out. The effect of the
      stationary phase polarity on the retention index was checked. In general, a
      greater retention index was found for the more polar stationary phase. The
      retention indices of the chlorobenzenes are greater than the retention indices of
      the methylbenzenes, irrespective of the stationary phase and the column
      temperature. In addition, the influence of the methyl/chlorine substitution on
      the benzene molecule was investigated at each temperature. The retention indices
      increased as the number of substituents (methyl/chlorine) increased. The
      retention index increments of methyl and chloro derivatives are also discussed,
      which permits to compare the effect of both, methyl or chlorine, chemical
      functions, for a fixed substituent number in the benzene molecule.

PMID- 15481261
TI  - Study of quantitative structure-mobility relationship of carboxylic and sulphonic
      acids in capillary electrophoresis.
AB  - A quantitative structure-mobility relationship (QSMR) was developed for the
      absolute mobilities of 115 carboxylic and sulphonic acids in capillary
      electrophoresis based on the descriptors calculated from the structure alone. The
      heuristic method (HM) and radial basis function neural networks (RBFNN) were
      utilized to construct the linear and nonlinear prediction models, respectively.
      The prediction results were in agreement with the experimental values. The HM
      model gave an root-mean-square (RMS) error of 3.76 electrophoretic mobility units
      for the training set, 5.59 for the test set, and 4.19 for the whole data set,
      while the RBFNN gave an RMS error of 1.78, 2.04, and 1.83, respectively. The
      heuristic linear model could give some insights into the factors that are likely
      to govern the mobilities of the compounds, however, the prediction results of the
      RBFNN model seem to be better than that of the heuristic method.

PMID- 15481262
TI  - Detailed study on simultaneous separation of rare earth elements by capillary
      electrophoresis.
AB  - Separation of all rare earth elements (REEs) by capillary zone electrophoresis
      was investigated in a system of alpha-hydroxyisobutyric acid (HIBA) as a main
      complex reagent and acetic acid (HAc) as an assistant complex reagent. In the
      combined system, ligand Ac- plays an important role in improving separation of Eu
      and Gd, and Y and Dy. The calculated ratio of Ac- to HIB- concentrations was
      compared and demonstrated that Eu and Gd, and Y and Dy tend to be separated at
      lower, and higher ratio of the two free ligands, respectively. An operational
      buffer system was developed for a complete separation of all REE ions.

PMID- 15481263
TI  - Determination of ammonium and metal ions by capillary electrophoresis-potential
      gradient detection using ionic liquid as background electrolyte and covalent
      coating reagent.
AB  - A capillary zone electrophoresis (CZE)-potential gradient detection (PGD) method
      coupled with field-amplified sample injection was developed to determine alkali
      metal, alkaline-earth metal, nickel, lead and ammonium ions. The capillary
      surface was coated with dialkylimidazolium-based ionic liquid and thus the
      electroosmotic flow (EOF) of the capillary was reversed. The buffer composed of
      7.5 mM lactic acid, 0.6 mM 18-crown-6, 12 mM alpha-cyclodextrin (alpha-CD); it
      was adjusted to pH 4.0 by 1-hexyl-3-methylimidazolium hydroxide. The 11 cations
      were baseline separated within 14 min with 5.1-18.9 x 10(4) plates (for 40-cm
      long capillary) in separation efficiency, and the detection limits were in the
      range of 0.27-7.3 ng/ml. The method showed good reproducibility in terms of
      migration time with RSD < or = 0.90% for run-to-run and < or = 1.65 for day-to
      day assessment.

PMID- 15481264
TI  - Preparation of polyaniline coating on a stainless-steel wire using electroplating
      and its application to the determination of six aromatic amines using headspace
      solid-phase microextraction.
AB  - A novel polyaniline (PANI) coating was prepared on a stainless-steel wire for
      solid-phase microextraction by electroplating method. For better mechanical
      strength, the stainless-steel wire was used instead of the fused silica fiber.
      The electroplating method had advantages of ease of preparation and simple
      equipments. The PANI fiber was evaluated by analyzing six aromatic amines
      (aniline, N,N-dimethylaniline, m-methylaniline, 2,4-dimethylaniline, 2
      chloroaniline, 3,4-dichloroaniline) in water. After the analytical procedure was
      optimized, the linearity was from 4.8 to 2.75 x 10(4) microg L(-1) and the
      detection limits was from 0.019 to 1.06 microg L(-1). Relative standard
      deviations were found to be 2.02-6.00%. Good recoveries were obtained when
      wastewater samples were analyzed.

PMID- 15481265
TI  - Monomeric C18 chromatographic method for the liquid chromatographic determination
      of lipophilic antioxidants in plants.
AB  - Reversed-phase liquid chromatography was used to determine lipophilic
      antioxidants in plants using two monomeric C18 columns operated at 30 degrees C
      and 4 degrees C, with a column-switching technique and acetonitrile-methanol
      gradient elution. The chromatograms were extracted at different wavelengths using
      a UV diode array detector (DAD). A wide range of plant antioxidants, including
      nine carotenoids (neoxanthin, violaxanthin, lutein, zeaxanthin, beta
      cryptoxanthin, lycopene, canthaxanthin, alpha-carotene and beta-carotene)
      together with all-trans-retinol, capsaicin, dihydrocapsaicin, chlorophyll a, and
      chlorophyll b can be separated within 50 min. Fluorometric detection was applied
      to quantify trace amounts of six vitamin E analogues (alpha-, delta- and gamma
      tocopherols and tocotrienols). The detection limits were 0.2-0.4 microg/g for
      various xanthophylls and 0.04-0.10 microg/g for vitamin E analogues.

PMID- 15481266
TI  - Pathogenesis of allergic bronchopulmonary aspergillosis and an evidence-based
      review of azoles in treatment.
AB  - BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a complex condition
      that affects people with asthma and cystic fibrosis (CF). It results from
      exposure to the fungus Aspergillus fumigatus, which leads to worsening airway
      inflammation and progressive damage to the lungs. The aim of this review is to
      outline the pathogenesis of the disorder, diagnostic criteria and to discuss the
      use of anti-fungal agents in its treatment. METHODS: The Cochrane library of
      systematic reviews and the Cochrane database of controlled trials were searched
      for controlled trials on ABPA and its treatment in both asthma and CF. In
      addition, articles included within the reviews were examined separately, and a
      separate search carried out using Medline. RESULTS: A systematic review for the
      use of azole anti-fungal agents in ABPA was identified for their use in both CF
      and non-CF-related disease. The review of ABPA alone identified two randomized
      controlled trials of itraconazole in chronic disease. These trials demonstrated
      improvements in symptoms and immune activation, but were short-term trials and
      failed to show a significant change in lung function. No trials were identified
      in CF. CONCLUSIONS: The use of anti-fungal agents in ABPA seems to be a rational
      one, with short-term efficacy demonstrated for the use of itraconazole. Further
      investigations are required to identify individuals who will benefit most from
      treatment and to establish the correct dose and means of delivering treatment in
      ABPA. Longer-term studies are required to demonstrate that treatment modifies the
      progressive decline in lung function seen with the disease.

PMID- 15481267
TI  - Clinical evaluation of the peak inspiratory flow generated by asthmatic children
      through the Novolizer.
AB  - STUDY OBJECTIVE: To assess whether asthmatic children may generate sufficient
      peak inspiratory flow through the Novolizer, a novel multiple dose dry powder
      inhaler with acoustic and optical feedback mechanisms for correct inhalation.
      PATIENTS AND METHODS: 137 children (median age 7 years, range 4-2) with mild to
      moderate persistent asthma (FEV1 < 90% predicted or pre-treated with low-dose
      steroids) participated in this open, multi-centre study. After assessment of FEV1
      and peak inspiratory flow (without inhalator device, PIF), the children were
      instructed to inhale with the Novolizer (PIF through inhaler, PIF-N). All
      assessments were done in triplicate and the mean out of three attempts analysed.
      RESULTS: Mean PIF was 128 +/- 61 l/min and mean PIF-N was 69 +/- 18 l/min. This
      is distinctly above the rate necessary to overcome the Novolizer's trigger
      threshold. PIF performance through the Novolizer was linear in the age interval
      of 4-8 years, no further increase was observed beyond 8 years. CONCLUSIONS: The
      medium to low intrinsic resistance of the Novolizer permits a relatively high PIF
      through this device. Together with the feedback mechanisms, this makes the
      Novolizer particularly valuable for inhalation therapy in asthmatic children with
      drugs such as salbutamol, formoterol, or budesonide.

PMID- 15481268
TI  - Knowledge of guidelines for the management of COPD: a survey of primary care
      physicians.
AB  - OBJECTIVES: To evaluate primary care physicians' knowledge of guidelines for the
      management of COPD. METHOD: Survey to 455 primary care physicians in private
      practice in the state of Geneva, Switzerland, and to 243 physicians practicing in
      Geneva University Hospital. RESULTS: Although 75% of respondents identified that
      the prevalence of COPD was increasing and 33% recognized it as a major public
      health issue, only 55% of physicians used spirometric criteria to define COPD,
      and one-third knew the correct GOLD criteria. Fifty-two percent felt
      uncomfortable with smoking cessation counselling. Sixty-two percent administered
      influenza vaccination annually and 29% had immunized their patients against
      Pneumococcus. Beta2-agonists were the first-line treatment for 89% of physicians,
      but 10% overestimated their clinical benefit. Twenty-five percent of respondents
      used systematically inhaled corticosteroids, but 46% ignored their indications.
      Oral corticosteroids were used by 42% of physicians outside of acute
      exacerbations. Seventy-nine percent thought that oral steroids had a beneficial
      effect on stable COPD. Finally, pulmonary rehabilitation was underused by 72% of
      physicians. CONCLUSIONS: This study shows major gaps in the knowledge of all core
      elements of guidelines for the management of COPD and identifies targets for
      future educational programs.

PMID- 15481269
TI  - Comparison of four demand oxygen delivery systems at rest and during exercise for
      chronic obstructive pulmonary disease.
AB  - OBJECTIVES: The aim of this study was to assess the performance of four demand
      oxygen delivery systems (DODS) in improving oxygenation and effort tolerance, at
      rest and during exercise, in chronic obstructive pulmonary disease (COPD)
      patients. MATERIALS AND METHODS: Thirteen COPD patients were prospectively
      included. Four DODS (Oxiclip, Versatile, Venture and Impulse) were compared with
      continuous-flow oxygen (CFO). Nine of these patients performed 6-min walking
      tests on room air and on 3 l/min oxygen by DODS and CFO; Oxygen saturation,
      walking distance and the Borg dyspnea score were recorded. RESULTS: With all four
      DODS devices arterial oxygenation was improved with lower oxygen flow rates than
      with CFO. Oxygen economy was best with Impulse, but at a cost of less
      satisfactory oxygenation. Exercise desaturation was similar with CFO, Oxiclip,
      Venture, and Impulse but significantly higher with Versatile (P < 0.05). Borg
      dyspnea scores were similar with CFO, Oxiclip, Venture, and Versatile but worse
      with Impulse (P < 0.05). There was no significant difference in walking
      distances. CONCLUSIONS: All four DODS improved oxygen saturation and saved
      oxygen. However, performance was better with the two devices (Oxiclip and
      Venture) that deliver a bolus of oxygen at inspiration onset.

PMID- 15481270
TI  - High-BAL fluid concentrations of RANTES in nonspecific interstitial pneumonia
      compared with usual interstitial pneumonia.
AB  - Chemokines such as regulated on activation, normal T-cell expressed and secreted
      (RANTES), monocyte chemoattractant protein (MCP)-1, monocyte inflammatory protein
      (MIP)-lalpha have been reported to play an important role in the pathogenesis of
      interstitial lung diseases. Among idiopathic interstitial pneumonia (IIP),
      nonspecific interstitial pneumonia (NSIP) has elevated percentages of Lymphocytes
      in bronchoalveolar lavage (BAL) fluid compared with usual interstitial pneumonia
      (UIP). These chemokines are candidate mediators for lymphocyte attraction to the
      lung in NSIR Therefore, we measured the BAL fluid levels of RANTES, MCP-1 and
      MIP1-alpha in 15 patients with idiopathic NSIP, 20 with idiopathic UIP, 22 with
      sarcoidosis and 12 healthy volunteers to evaluate the contribution of these
      chemokines using enzyme-linked immunosorbent assays. The levels of RANTES in BAL
      fluid were significantly higher in patients with NSIP compared with healthy
      volunteers (P < 0.01), UIP and sarcoidosis (P < 0.05). In MCP-1, the levels in
      BAL fluid of NSIP and UIP patients were significantly elevated compared with
      healthy volunteers and sarcoidosis patients (P < 0.01). These results suggest
      that RANTES and MCP-1 in BAL fluid may play an important role in inflammatory
      cell recruitment to the lung in idiopathic NSIP as well as other interstitial
      lung diseases.

PMID- 15481271
TI  - Is it possible to distinguish between atypical pneumonia and bacterial
      pneumonia?: evaluation of the guidelines for community-acquired pneumonia in
      Japan.
AB  - The Japanese Respiratory Society (JRS) published the guidelines for the
      management of community-acquired pneumonia in 2000. The guidelines set up nine
      parameters and criteria for the differential diagnosis of atypical pneumonia and
      bacterial pneumonia based on clinical symptoms, physical signs and laboratory
      data. To evaluate the performance of these guideline criteria, 91 cases of
      Chlamydia pneumoniae (53 cases were pure-C. pneumoniae and 38 cases were mixed-C.
      pneumoniae pneumonia), 103 cases of Mycoplasma pneumoniae (86 cases were pure-M.
      pneumoniae and 17 cases were mixed-M. pneumoniae pneumonia) and 144 cases of
      bacterial (Streptococcus pneumoniae and/or Haemophilus influenzae) pneumonia were
      analyzed. The accordance rate for a suspected atypical pneumonia with the
      guideline criteria was 84.8% for pure-M. pneumoniae pneumonia and 60.3% for pure
      C. pneumoniae pneumonia, but only 9.0% for bacterial pneumonia, 12.1% for mixed
      C. pneumoniae pneumonia and 16.6% for mixed-M. pneumoniae pneumonia. Overall, the
      sensitivity and specificity of the criteria in the JRS guidelines were 75.5% and
      90.9%, respectively. Our results indicated that the differentiation of pneumonia
      in the JRS guidelines is useful for the diagnosis of M. pneumoniae pneumonia, but
      difficult to apply to the diagnosis of C. pneumoniae pneumonia.

PMID- 15481272
TI  - Benefits at 1 year of nocturnal intermittent positive pressure ventilation in
      patients with obesity-hypoventi lation syndrome.
AB  - BACKGROUND: Patients with the obesity-hypoventilation syndrome (OHS) benefit from
      non-invasive ventilatory support. We assessed the long-term physiopathological
      response to 12-months of nocturnal ventilatory assistance at home with bi-level
      positive airway pressure (BiPAP) via nasal mask in patients with this disease.
      METHODS: A series of 13 non-consecutive patients diagnosed of OHS (5 men and 8
      women) with a mean (SD) age of 61.9 (8) years, underwent the following studies
      before (baseline) and after 12 months of non-invasive domiciliary mechanical
      ventilation: arterial blood gases, nocturnal digital pulse oximetry, spirometry,
      body plethysmography, maximum muscular respiratory pressures and ventilatory
      pattern with measurement of occlusion pressure (P0.1) before and after
      hypercapnia. An overnight cardiorespiratory polygraphy was done at baseline.
      RESULTS: After 12 months of non-invasive mechanical ventilation, there were
      significant (P < 0.05) reductions of arterial carbon dioxide tension (PaCO2) and
      increases in arterial oxygen tension, forced vital capacity and ventilatory
      response to hypercapnia, as measured by the relationship between changes of P0.1
      and PaCO2 (deltaP0.1 / deltaPaCO2) as well as respiratory minute volume (V(E))
      and PaCO2 (deltaV(E) / deltaPaCO2). Changes of the PaCO2 correlated significantly
      with those in the (deltaP0.1 / deltaPaCO2) slope (r = 0.576, P < 0.05).
      CONCLUSIONS: The present results confirm that non-invasive home mechanical
      ventilation is an effective approach for long-term treatment of OHS.

PMID- 15481273
TI  - Health-related quality of life in patients with obstructive sleep apnea: effects
      of long-term positive airway pressure treatment.
AB  - The aim of the present study was to determine the effect of middle and long-term
      positive airway pressure (CPAP) treatment on the health-related quality of life
      in patients with obstructive sleep apnea. We prospectively studied two groups of
      patients with this disease; a group of 42 patients (33 men and 9 women) with a
      mean age of 55.2 +/- 7.4 years and a body mass index of 33.5 +/- 6.4 kg/m2
      treated with CPAP for 6-months, and another group of 42 patients (34 men and 8
      women) with a mean age of 54.4 +/- 10.5 years and a body mass index of 33.2 +/-
      4.0 kg/m2 treated with CPAP for 18-months. The health related quality of life was
      assessed by administering a Medical Outcomes Study Short Form-36 (SF-36)
      questionnaire before and after CPAP therapy. Patients treated with CPAP for 6
      months only improved significantly in the vitality dimension and this change was
      clinically relevant (standard error of the measurement = 1.43 SEmeas). In
      contrast, those treated with CPAP for a long period (18-month) showed
      statistically significant improvement at post-treatment in five SF-36 dimensions:
      physical functioning (P < 0.001), role physical (P < 0.01), social functioning (P
      < 0.01), vitality (P < 0.001), and general health perception (P < 0.001). In four
      of these dimensions the improvement was clinically relevant: role physical (1.16
      SEmeas), social functioning (1.35 SEmeas), vitality (1.35 SEmeas), and general
      health perception (2.05 SEmeas). Using two different global rating of change
      (independent measures or anchors), the minimal change important difference for
      patients treated with CPAP for 6 months ranged from 20.7 to 24.2 points on the
      vitality dimension; and for patients with CPAP for 18-months it ranged from 2.5
      to 7.5 points on the physical role, 5.5-6.6 points on social functioning, 7.5-8.7
      on vitality, and 13.5-15.5 on general health perception dimension. We conclude
      that health-related quality of life of obstructive sleep apnea patients improves
      with long term CPAP treatment and these changes are clinically relevant in
      several health dimensions.

PMID- 15481274
TI  - Induced sputum and bronchoalveolar lavage from patients with hypersensitivity
      pneumonitis.
AB  - BACKGROUND AND AIM: Hypersensitivity pneumonitis (HP) is an immunologically
      induced inflammation of the lung parenchyma, though bronchial airways may be also
      involved. The aim of this study was to compare the cellular profiles of induced
      sputum (IS) in patients with newly diagnosed HP to that of healthy subjects, and
      to examine the relationship between inflammatory cells from IS and BAL. METHODS:
      Nine HP patients and 9 healthy volunteers were studied. IS was obtained by
      inhalation of hypertonic saline solution in all subjects. Bronchoscopy was
      performed on a different occasion in all patients and in five controls. RESULTS:
      IS was well tolerated and preferred to BAL by all subjects. Both IS and BAL from
      HP patients showed a significant increase in total cells (P < 0.02 and P < 0.001)
      and in lymphocytes (P < 0.02 and P < 0.001) and a significant decrease in
      macrophages (P < 0.05 and P < 0.001), when compared with normal subjects. In HP
      patients, total cells number in IS was higher than that in BAL (P < 0.02).
      Moreover, the percentage of lymphocytes was significantly lower in IS than in BAL
      (P < 0.001). No significant relationship was found between total cells or
      inflammatory cells from IS and the corresponding ones from BAL and wide limits of
      agreement were found between lymphocytes from IS and BAL. CONCLUSIONS: This study
      demonstrated that both BAL and IS from newly diagnosed HP patients contained
      significantly more total cells and lymphocytes, when compared to healthy
      subjects. Moreover, differential cell counts in HP patients showed that IS and
      BAL reflected different compartments of inflammation. Thus, IS could represent a
      complementary, but not alternative tool to bronchoscopy both in research and in
      the clinical monitoring of HP patients.

PMID- 15481275
TI  - Gender differences in obstructive sleep apnea syndrome: a clinical study of 1166
      patients.
AB  - The objective of this study was to compare the frequency of some sociocultural,
      clinical, and anthropometric data between men and women in a sample of 1745
      patients referred to a Sleep Unit for symptoms of obstructive sleep apnea (OSA).
      A standardized questionnaire was administered and anthropometric data were
      measured. Patients underwent a polysomnography (during a night or a nap) or an
      overnight home cardiorespiratory polygraphy. A total of 1166 patients
      (male/female ratio 4.9:1) fulfilled criteria of OSA (apnea-hypopnea index > or =
      10). Women were employed, habitual drivers or workers at risk occupations in a
      lower percentage than men. Women came to the clinical interview accompanied by
      their partner less frequently than men. The frequency of snoring and daytime
      hypersomnolence was similar in both genders, although witnessed apneas were more
      frequent in males. Fatigue, morning headaches, insomnia, depression and use of
      sedatives were more frequent in women than in men. Women were older than men,
      more obese (although with an obesity pattern less centrally distributed), and
      referred hypertension more frequently. It is concluded that it is likely that
      women with OSA may be underdiagnosed due to circumstances related to the family
      lifestyle and sociocultural factors in addition to different OSA clinical
      expression.

PMID- 15481276
TI  - Single-isomer R-salbutamol is not superior to racemate regarding protection for
      bronchial hyperresponsiveness.
AB  - Bronchial hyper-reactivity (BHR) has been suggested to follow cessation of
      regular medication with racemic salbutamol. This study aimed at investigating the
      effects from medication with R,S- and R-salbutamol on bronchial response to
      provocation with isocapnic hyperventilation of cold air (IHCA). Twenty-six
      patients with mild to moderate asthma were enrolled in a double-blind,
      randomised, cross-over study. Bronchial response to provocation was measured
      before and after 1 week's medication. Doses of 0.63 mg R-salbutamol or 1.25 mg
      R/S-salbutamol were inhaled three times daily during medication-weeks and a wash
      out week intervened. Tests were performed 6 h after the last dose of test drug.
      Impulse oscillometry and forced expiratory volume during one second were methods
      used to identify bronchial response to provocation. Two patients withdrew from
      the investigation due to side-effects, one from R- the other from R,S-salbutamol.
      Comparable resting bronchial conditions were indicated by differences in baseline
      lung function values of <2% between study days. No statistically significant
      medication-dependent differences in BHR could be demonstrated between treatment
      groups. However, 15 patients exhibited higher (P = 0.03) post-treatment BHR after
      pure R-salbutamol than after R,S-salbutamol. Furthermore, plasma concentrations
      of R-salbutamol tended to be lower (P = 0.08) after medication with R- than after
      R,S-salbutamol despite equal doses of R-salbutamol given during the two separate
      treatment periods. We also found that considerable amounts of S-salbutamol were
      retrieved in plasma after medication with pure R-salbutamol. We conclude that we
      were unable to demonstrate favourable effects of R-salbutamol over R,S-salbutamol
      regarding response to provocation with IHCA after regular medication of 1 week's
      duration.

PMID- 15481277
TI  - Heavy resistance training increases muscle size, strength and physical function
      in elderly male COPD-patients--a pilot study.
AB  - This study investigated the effects of heavy resistance training in elderly males
      with chronic obstructive pulmonary disease (COPD). 18 Home-dwelling male patients
      (age range: 65-80 years), with a mean forced expiratory volume in the first
      second (FEV1) of 46 +/- 3.4% of predicted value, were recruited. Baseline and
      post-training assessments included: Cross-sectional area (CSA) of quadriceps
      assessed by MRI, isometric and isokinetic knee extension strength, isometric
      trunk strength, leg extension power, normal and maximal gait-speed on a 30 m
      track, stair climbing time, number of chair stands in 30 s, lung function (FEV1)
      and self-reported health. Subjects were randomized to a resistance training group
      (RE, n = 9) or a control group conducting breathing exercises (CON, n = 9). RE
      performed heavy progressive resistance training twice a week for 12 weeks. 6 RE
      and 7 CON completed the study. In RE the following improved (P < 0.05):
      Quadriceps CSA: 4%, isometric knee extension strength: 14%, isokinetic knee
      extension strength at 60 degrees /s.: 18%, leg extension power: 19%, maximal gait
      speed: 14%, stair climbing time: 17%, isometric trunk flexion: 5% and self
      reported health. In CON no changes were found. In conclusion, 12 weeks of heavy
      resistance training twice a week resulted in significant improvements in muscle
      size, knee extension strength, leg extension power, functional performance and
      self-reported health in elderly male COPD patients.

PMID- 15481278
TI  - Initiation of maintenance treatment of persistent asthma: salmeterol/fluticasone
      propionate combination treatment is more effective than inhaled steroid alone.
AB  - OBJECTIVE: To determine whether initiation of maintenance treatment with the
      salmeterol (S)/fluticasone propionate (FP) combination (Seretide/Viani/Advair) is
      more effective than inhaled steroid alone in patients with asthma symptomatic on
      short-acting bronchodilator alone. DESIGN: 150 asthma patients with symptoms and
      prn use of short-acting bronchodilator at least once a week were randomised to 24
      weeks' treatment with either S/FP 50/100 microg bd (n = 78) or FP 100 microg bd
      (n = 72). The primary endpoint was the percentage of symptom-free 'day + night's.
      RESULTS: The percentage of symptom-free 'day + night's increased significantly
      more for S/FP (20 to 64%) compared to FP (24 to 51%). The treatment difference
      was 15.3%, P = 0.008. In the sub-group of patients with mild asthma the treatment
      difference was also statistically significant in favour of S/FP (P = 0.0245, n =
      74). S/FP was also significantly superior to FP alone for: lung function,
      salbutamol use prn, day symptom score, symptom-free days, and episode-free 'day +
      night's. Treatments were equally well tolerated. CONCLUSION: Initial maintenance
      treatment with S/FP is significantly more effective than with inhaled steroid
      alone for patients symptomatic when treated with short-acting bronchodilator
      alone. This also apply to patients with mild persistent asthma.

PMID- 15481279
TI  - A prospective clinical study of theophylline safety in 3810 elderly with asthma
      or COPD.
AB  - A large-scale prospective study was conducted in 3810 Japanese elderly (> or =65
      years old) patients with asthma or chronic obstructive pulmonary disease (COPD)
      who had been treated with sustained-release theophylline tablets (THEODUR) at a
      dose of 400 mg/day for 1-6 months, in principle. Among 3798 protocol-complying
      patients (mean age: 73.8 +/- 0.10 years, 1997 with COPD), 261 theophylline
      related adverse events were observed in 179 (4.71%) patients. The 5 most
      frequently observed adverse events were "nausea" (40 episodes, 1.05%), "loss of
      appetite" (22 episodes, 0.56%), "hyperuricemia" (16 episodes, 0.42%),
      "palpitation" (15 episodes, 0.39%), and "increased alkaline phosphatase" (11
      episodes, 0.28%). No convulsions were reported. Six patients had serious adverse
      events. The incidence of theophylline-related adverse events was higher in
      patients with hepatic disease (odds ratio: 1:1.81) and in patients with
      arrhythmia (odds ratio: 1:1.88). Blood drug concentration measurements in 736
      patients indicated that the drug levels were < or =15 microg/ml in 641 patients
      (87.1%), and no correlation was noted between dose and theophylline-related
      adverse events. These results suggest that sustained-release theophylline can be
      used safely in elderly patients with asthma or COPD.

PMID- 15481280
TI  - Relations between respiratory symptoms and spirometric values in young adults:
      the European community respiratory health study.
AB  - We aim to assess whether respiratory symptoms are associated with lung function
      in young adults, and whether any such relation is similar in those with asthma,
      in men and women, and in different countries. Study participants (aged 20-44
      years) were randomly selected from the general population in 35 centres in 15
      countries as part of the European Community Respiratory Health Study. In all,
      12,541 subjects (47%) completed a respiratory symptoms questionnaire and
      spirometry, metacholine challenge and immunoglobulin E tests. Indicators of
      diagnosed asthma showed the largest association with airways obstruction (FEV1-
      maximal 1-s forced expiratory volume/forced vital capacity--FVC < 70%), followed
      by symptoms of wheezing or shortness of breath, in both genders. Among the 96% of
      subjects whose FEV1/FVC ratios were greater or equal to 70%, wheezing or
      shortness of breath was associated with lower FEV1 levels (-211 ml in men and 
      169 ml in women (P < 0.01)), independent of diagnosed asthma, smoking, atopy or
      bronchial responsiveness. This association was not explained by a lower FVC.
      Symptoms of chronic bronchial mucus hypersecretion (chronic phlegm) were
      unrelated to both airways obstruction and FEV1 levels. Findings were homogeneous
      across all centres. These results suggest that lung diseases that cause wheezing
      are generally associated with impaired lung function.

PMID- 15481281
TI  - Decision making in asthma therapy--what is important in clinical practice?

PMID- 15481282
TI  - The size of the problem of managing asthma.
AB  - Asthma is now the commonest chronic disease in industrialised countries and its
      prevalence is rising throughout the world. However, despite the availability of
      very effective treatments many patients with asthma have poorly controlled
      symptoms and frequent exacerbations, some of which require hospital admission.
      Important factors contributing to poor asthma control are failure to recognise
      asthma as a diagnosis, non-implementation of asthma management guidelines and
      patient non-compliance with therapy. The guidelines themselves have many inherent
      limitations. Chief among these is that the evidence upon which they are based may
      be misleading. The evidence used to support recommendations in guidelines is
      derived from double-blind, placebo-controlled studies in very carefully selected
      patients who are usually compliant with therapy and instructed in the use of
      inhalers. In the 'real world' things are very different and patients frequently
      fail to understand how to use their therapy and are often non-compliant. Reasons
      for non-compliance are complex and include complicated drug and dosing regimens
      and inability to use inhaler devices correctly; particularly pressurised metered
      dose inhalers (pMDIs) due to difficulty co-ordinating device activation and
      inhalation. Dry powder inhalers (DPIs) preclude the need to co-ordinate
      inspiration with activation, are easy and convenient to use and are
      environmentally friendly. There is no doubt that the type of inhaler is just as
      important as the class of drug in the long-term management of asthma.
      Improvements in inhaled drug delivery will continue to be important in improving
      asthma management.

PMID- 15481283
TI  - How do we measure the effectiveness of inhaled corticosteroids in clinical
      studies?
AB  - Inhaled corticosteroids (ICSs) are the gold standard anti-inflammatory therapy
      for asthma and have been studied using a variety of different clinical trial
      designs. In long-term comparative studies ICSs are more effective in controlling
      asthma than beta-agonists or leukotriene antagonists (LTAs). Efficacy has also
      been shown retrospectively, as patients frequently experience an exacerbation of
      their asthma upon withdrawal of ICSs, whilst the regular use of low dose ICSs
      prevents death from asthma. The combination of ICSs with long-acting beta2
      agonists (LABAs) is effective for patients with asthma non-responsive to low
      doses of ICSs, particularly in reducing exacerbations. In shorter term studies a
      modest dose-response effect of ICSs has been shown for lung function, symptom
      control and oral corticosteroid use in asthmatic patients. ICSs are also
      effective in reducing airway hyperresponsiveness (AHR) to various stimuli, as
      well as reducing exhaled nitric oxide (NO) concentrations and the number and
      activation state of a wide variety of inflammatory cells. Finally, using allergen
      challenge models even single doses of ICSs have profound inhibitory effects on
      the late asthmatic reaction. Since ICSs are the mainstay of asthma management
      guidelines, it is important that novel therapies should be judged against ICSs in
      future clinical trials. There are many potential designs for these comparative
      studies.

PMID- 15481284
TI  - Tools to assess (and achieve?) long-term asthma control.
AB  - Assessment tools are needed to monitor asthma control and to detect exacerbations
      before the alteration of functional parameters and the occurrence of symptoms.
      The ability to effectively monitor asthma control would enable clinicians to
      increase corticosteroid dose or to stop corticosteroid tapering before symptoms
      occur. As a few severe exacerbations are expected per year in treated patients,
      these tools must be suitable for long-term use. They must also be reproducible,
      acceptable to patients and be non-invasive. Tools currently available to assess
      asthma control include assessment of: clinical parameters (e.g. nocturnal
      awakenings; bronchodilator intake; symptom scores); lung function (e.g. peak
      expiratory flow and forced expiratory volume in 1 s); subjective parameters of
      asthma control (e.g. asthma control questionnaire (ACQ)); bronchial hyper
      responsiveness; eosinophilia in induced sputum; and exhaled nitric oxide (NO)
      concentration. Clinical symptoms, lung function and the ACQ have proved to be
      inadequate markers of asthma control, as changes in these parameters occur at the
      same time as symptom manifestation. By contrast, sputum eosinophilia and exhaled
      NO concentrations are truly predictive of asthma exacerbations; monitoring these
      parameters are useful in preventing exacerbations from occurring in the first
      instance. They also assess, and help to achieve asthma control in the long term.

PMID- 15481285
TI  - Successful use of DPI systems in asthmatic patients--key parameters.
AB  - Effective inhalation therapy using pressurised metered dose inhalers (pMDIs) and
      dry powder inhalers (DPIs) is the cornerstone of asthma management. Previous
      studies have demonstrated difficulties in the usage of pMDIs in certain patient
      groups, especially as pMDis require the co-ordination of inhaler activation with
      dose inhalation. Almost all DPIs are breath-activated and preclude the need to co
      ordinate activation with inspiration. Three key parameters for successful inhaler
      use should be considered when evaluating existing or future DPI devices: (1)
      compliance; (2) fine particle distribution and dependency on inspiratory flow
      and; (3) clinical efficacy. A threshold mechanism which controls for a minimal
      inspiratory flow rate is desirable in order to support formation of an optimal
      fine particle fraction (FPF) which in turn improves lung deposition.
      Additionally, in order to enhance patient compliance an optimal multidose DPI
      should feature a visual or acoustic feedback of a correct inhalation. The
      Novolizer is a multidose refillable DPI. It has multiple feedback mechanisms and
      a trigger flow valve system, which helps to ensure correct inhalation that allows
      adequate lung deposition, helps to reassure the patient that medication has been
      taken and might therefore improve patient compliance. The low-to-medium airflow
      resistance translates into higher peak inspiratory flow (PIF) and makes the
      Novolizer DPI particularly suitable for the use in patients with reduced
      inspiratory flow rates. Clinical studies have shown that children, elderly
      patients, adults with moderate-to-severe asthma and COPD patients (stage IIa-III)
      are able to generate sufficient inspiratory flow to operate the Novolizer
      effectively. In contrast previous studies with other MDPIs (e.g. Turbuhaler or
      Aerolizer) demonstrated that in patient groups with severe obstructive lung
      disease or in children with asthma optimal inspiratory flow rates are not
      achieved in all patients.

PMID- 15481286
TI  - Guidelines versus clinical practice--which therapy and which device?
AB  - Inhalation therapy delivers therapeutic agents directly into the lungs of
      patients with asthma, and is likely to remain the route of delivery of choice for
      the foreseeable future. The majority of patients with asthma suffer from mild
      intermittent to mild persistent disease for which regular low dose inhaled
      corticosteroids and on demand short-acting beta2-agonists have been recommended.
      These highly effective anti-asthma medications are readily available, and so in
      the future improvement in asthma therapy will most Likely derive from
      improvements in inhaler technology. Dry powder inhalers (DPIs) have many
      advantages compared to chlorofluorocarbon pressurised metered dose inhalers. Most
      notably, with DPIs patients no longer need to co-ordinate activation of the
      inhaler with inspiration. The Novolizer (VIATRIS, Germany) which is one of the
      latest developments in DPI technology offers a number of features required to
      increase the safety and efficacy of inhaled therapy. It is the first DPI to
      include an inspiratory trigger threshold, which helps to prevent sub-optimal dose
      administration. Repeated activation without inhalation is mechanically inhibited
      by an overdose prevention mechanism. In conclusion, there is good evidence that
      technically refined DPIs are more likely to advance inhaled anti-asthmatic
      therapy than newly developed inhaled drugs. This is important when inhalation
      therapy is considered not only for asthma but also for chronic obstructive
      pulmonary disease.

PMID- 15481287
TI  - How to achieve good compliance with inhaled asthma therapy.
AB  - Inability to use inhaler devices correctly is a major source of non-compliance in
      patients with asthma. The problem of coordinating dose release with inspiration
      seen with pressurised metered dose inhalers (pMDIs) is overcome by dry powder
      inhalers (DPIs), since they use inspiratory flow energy to carry the drug dose to
      the respiratory tract. The first DPIs were not popular because they were single
      dose devices and inconvenient to use. The introduction of multiple dose DPIs
      improved the image of the dry powder systems in the eyes of both the clinician
      and the patient. The continued development of DPIs has led to inhaler devices
      which include dose counters, are easy to use, are refillable and provide feedback
      to the patient on a correct inhalation. Criteria that may improve patient
      compliance with an inhaler include: correct use of the device by most patients;
      ease and convenience of device use; dose release even at low inspiratory flow
      rates; feedback of drug release which could instill confidence that the dose has
      been inhaled; cartridge refills and overall confidence in the device. The
      Novolizer has all the desirable features listed above and is expected to improve
      compliance if prescribed for the large number of patients who cannot use the
      conventional pMDI or less efficient DPSs.

PMID- 15481288
TI  - Cholangiocarcinoma: advocate an aggressive operative approach with adjuvant
      chemotherapy.
AB  - Cholangiocarcinoma presents many challenges. Prognosis is thought to be
      determined by conventional predictors of survival; margin status, pathologic
      criteria, stage, and comorbid disease. Ninety-four patients, 57 males and 37
      females, underwent resections for cholangiocarcinoma between 1989 and 2000.
      Thirty-two patients (34%) had distal tumors, 10 had midduct lesions, and 52 had
      proximal/intrahepatic lesions. Thirty-four patients underwent
      pancreaticoduodenectomies, 23 bile duct resections alone, and 37 bile duct and
      concomitant hepatic resections. Tumor location did not influence mean survival
      (distal, 28 months +/- 23; midduct, 28 months +/- 21; and proximal, 31 months +/-
      36). Operation undertaken did not alter survival (bile duct resection, 30 months
      +/- 37; pancreaticoduodenectomy, 27 months +/- 23; and concomitant bile
      duct/hepatic resection, 32 months +/- 32). TNM stage failed to predict survival:
      5 stage I (29 months +/- 22), 12 stage II (41 months +/- 33), 12 stage III (33
      months +/- 19), and 64 stage IV (27 months +/- 32). Tumor size did not influence
      survival: T1-2 (32 months +/- 33) versus T3-4 lesions (29 months +/- 25). Mean
      survival with negative margin (n = 67) was 34 months +/- 33, whereas
      microscopically positive (n = 13, 23.9 months +/- 25) or grossly positive (n =
      14, 20.4 months +/- 20) margins were predictive of significantly shorter survival
      (P < 0.03). Adjuvant treatment (n = 41) was associated with significantly longer
      survival (40.5 months +/- 36) than those who received no further therapy (n = 53;
      24 months +/- 24) (P = 0.05). TNM stage, tumor size, operation undertaken, and
      location were not associated with duration of survival after resection. Margin
      status was associated with duration of survival, though extended survival is
      possible even with positive margins. Advanced stage should not preclude
      aggressive resection. Without specific contraindications, an aggressive operative
      approach is advocated followed by adjuvant therapy.

PMID- 15481289
TI  - Colonoscopic perforations: incidence, management, and outcomes.
AB  - Fiberoptic colonoscopy provides superior diagnostic and therapeutic capabilities
      in the treatment of lower gastrointestinal disease processes. A well-recognized,
      but uncommon, complication during the procedure is perforation. The purpose of
      this study was to determine the incidence of colonoscopic perforation, define
      risk factors, assess the management of these complications, and evaluate
      outcomes. From January 1997 through December 2003, 43,609 colonoscopies were
      performed in our medical center. There were 14 (0.032%) perforations (1 in 3115
      procedures); 7 from diagnostic and 7 from therapeutic procedures. General
      surgeons performed 1243 procedures (2.9%), and their rate of perforation was
      0.080 per cent compared with 0.031 per cent for gastroenterologists during the
      same period. Half of the perforations occurred in the rectosigmoid, and the most
      common mechanism was mechanical (n = 6). Perforation was identified immediately
      during endoscopy in 50 per cent of the patients. Thirteen of 14 perforations were
      treated within 24 hours; 1 was delayed 48 hours. Initial surgical management was
      undertaken in 11/14 patients. Initial nonoperative treatment was attempted in
      three and was successful in only one patient. The mean length of stay following
      perforation was 11.2 days (range, 4-36 days). Three patients (21.4%) had 7
      postoperative complications. Colonoscopic perforations are uncommon but can be
      recognized early and managed surgically with acceptable morbidity and
      postoperative length of stay.

PMID- 15481290
TI  - Outcomes of laparoscopic versus open appendectomy.
AB  - Controversy remains regarding which approach is better, laparoscopic appendectomy
      (LA) or open appendectomy (OA). A 5-year retrospective review of patients
      undergoing appendectomy was performed to compare the outcomes of LA and OA using
      standard statistical methods (P < 0.05). LA was performed in 207 and OA in 100
      patients (conversion 6.7%). Females underwent LA more frequently than males
      (81.7% vs 51.9%; P = 0.0001). LA patients were older (30.2 years vs 25.7 years; P
      = 0.03), with no differences in body mass index (BMI) (27.9 kg/m2 vs 25.5 kg/m2;
      P = 0.06) or operative times (51.1 minutes vs 51.5 minutes; P = 0.84). LA
      patients required less analgesics (19.2 mg vs 31.5 mg; P = 0.01), and shorter
      hospital stays (27.2 hours vs 53.1 hours; P = 0.0001). Operating room charges
      were higher for LA (3839 dollars vs 2528 dollars; P = 0.0001), with no difference
      in total hospital charges (8801 dollars vs 9147 dollars; P = 0.14). Complications
      between LA and OA were similar (3.6% vs 8%; P = 0.12). Converted patients were
      older, required more analgesia, and had higher morbidity, length of stay, and
      hospital charges. LA is the procedure of choice for appendicitis regardless of
      age, sex, BMI, or degree of appendiceal inflammation. LA is as safe and quick to
      perform as OA with lower analgesic requirements, length of stay, and no
      difference in total charges.

PMID- 15481291
TI  - A novel intestinal anastomotic device in a porcine model.
AB  - The purpose of this study was to evaluate a novel, intraluminally deployed
      anastomotic device (AD). A survival study was conducted in 18 farm pigs. One
      early subject was excluded and replaced due to premature expiration. Six animals
      were placed in 1 of 3 cohorts, with euthanasia and AD explantation planned at 2,
      4, and 6 weeks. A distal small intestinal side-side [functional end-end]
      anastomosis using the AD was performed via midline laparotomy. Fluoroscopy with
      double-contrast dilute barium and burst pressure measurements were performed in 4
      animals in each group. Two animals in each cohort underwent fluoroscopy without
      contrast and resection for histology. Mucosal healing, inflammation, anastomotic
      alignment of the muscularis propria, and fibrosis were graded on a 4-point scale.
      All animals survived to the date of planned euthanasia except the excluded
      subject, who expired from causes unrelated to the device. Normal weight gain was
      seen in all. Sixteen of 18 devices sloughed prior to extraction without evidence
      of injury or obstruction during the survival period or at necropsy. Filling
      pressures of >200 mm Hg were reached; no leakage was seen. Mucosal healing and
      continuity were graded good to excellent at 2 weeks and excellent at 4 and 6
      weeks. Inflammation improved with time, with moderate change at 2 weeks and mild
      at 6 weeks. Anastomotic fibrosis was mild at 2 weeks, mild to minimal at 4 weeks,
      and minimal at 6 weeks. The anastomotic alignment was 100 per cent except in 1
      animal at 2 weeks with >50 per cent but <100 per cent alignment. The AD resulted
      in a stable, functional anastomosis without narrowing. All tested anastomoses
      withstood supraphysiologic insufflation pressures without evidence of disruption.
      The applicability of this novel device will be explored for use in other
      gastrointestinal and biliary anastomoses using minimally invasive deployment
      techniques.

PMID- 15481292
TI  - Intussusception secondary to metastasis from a low-grade retroperitoneal
      liposarcoma.
AB  - Liposarcomas are the most prevalent soft tissue sarcomas in adults. Low-grade
      liposarcomas are the most frequent and least aggressive and are noted as having a
      low risk of metastasis. We present a case of low-grade myxoid liposarcoma that
      metastasized to the small bowel resulting in intussusception. This case involves
      a 44-year-old woman with a recurrent retroperitoneal liposarcoma. Approximately
      30 months after initial diagnosis, the patient was found to have a solitary
      metastasis to the small bowel that presented as a jejunal intussusception.
      Interestingly, there was no indication of a round cell component in either the
      metastasis or recurrent tumor, although the original tumor did contain a small
      round cell component. This is the first report in the English literature of
      liposarcoma metastasizing to the small bowel. We suggest that atypical
      presentations of liposarcoma metastases should always be considered in the
      management of patients with a history of liposarcoma.

PMID- 15481293
TI  - Reduced social morbidity of laparoscopic appendectomy in children.
AB  - Laparoscopic appendectomy has not been uniformly adopted by pediatric surgeons.
      Our children's hospital adopted laparoscopic appendectomy due to perceived
      benefits to patients and their families. We hypothesized that laparoscopic
      appendectomy in children resulted in less social morbidity than those undergoing
      open appendectomy. A questionnaire focused on a set of postoperative variables
      affecting the patient's and the family's return to normal activities. Families
      expressed their answers as a range of days. Five different ranges were assigned a
      numerical value for 10 different social morbidity variables. The numerical values
      were analyzed using Pearson chi2 test; statistical significance was defined as P
      < 0.05. The response rate was 55 per cent (134 of 244). Seventy-four had open and
      47 laparoscopic appendectomy with a comparable incidence of acute and perforated
      appendicitis. Children undergoing laparoscopic appendectomy had shorter hospital
      stays and earlier resumption of feeding, return to school, return to pain-free
      walking and stair climbing, and resumption of normal activities including gym.
      Additionally, they had fewer wound problems, shorter duration of oral pain
      medication usage, and their parents returned to work quicker than the open group.
      All these were statistically significant. Laparoscopic appendectomy results in
      significantly reduced social morbidity for children and their families.

PMID- 15481294
TI  - Language barrier leads to the unnecessary intubation of trauma patients.
AB  - Airway evaluation in trauma patients is performed immediately upon patient
      contact, with communication being a vital component to this exam. Language and
      communication barriers may lead to the unnecessary placement of an artificial
      airway with resultant patient risk and elevation of health care costs. The
      objective of our study was to evaluate potentially preventable intubations in
      Spanish-speaking patients. A 9-year retrospective review was performed using the
      National Trauma Registry for The American College of Surgeons (NTRACS) database.
      We evaluated patients intubated on arrival to the trauma center and remaining
      intubated for less than 48 hours. Deaths were excluded. Patients who typically
      speak English were compared with patients who typically speak Spanish. Mechanism
      of injury (MOI), hypotension during resuscitation (HDR), illicit substance use,
      alcohol use, mean Glasgow Coma Score (GCS), mean Injury Severity Score (ISS),
      payer source, and hospital cost were compared. Forty-nine per cent and 38 per
      cent of Spanish and English speaking individuals, respectively, were intubated
      for less than 48 hours (P = 0.072). MOI, HDR, ISS, illicit substance use, alcohol
      use, and payer source were similar. GCS was statistically higher in the Spanish
      speaking group (14 vs 12; P = 0.004). Language and communication barriers lead to
      potentially preventable intubations in trauma patients.

PMID- 15481295
TI  - Infectious complications after hepatic resection.
AB  - The purpose of this study was to assess the characteristics of surgical
      infections after hepatic resection (HR) to identify factors accounting for
      increased postoperative mortality. Advances in operative technique and care have
      decreased morbidity and mortality after HR. However, infections after HR continue
      to be a major contributor to postoperative morbidity and mortality. All HR done
      during a 7-year period were analyzed and compared to our prospective surgical
      infection database. Factors contributing to infectious complications and
      mortality were identified. HR (n = 207) were performed with an overall mortality
      of 5.8 per cent. Nine patients (3.3%) had 18 infections; 6 (60%) had multiple
      infection sites, most commonly the peritoneum, blood, or wound. Three infected
      patients died. Lung and line infections occurred in 2 (67%) infection-related
      deaths. No single comorbidity increased postoperative infection risk, but an
      average of 6.7 comorbid conditions were present. All infection-related deaths
      were associated with ventilator-dependence. All infection-related deaths occurred
      after resection of a mean of four segments. Additional procedures at the time of
      HR, operative drains, or transfusion requirements did not impact infectious
      complications or mortality. Methicillin-resistant Staphylococcus sp. was isolated
      in all infection-related deaths. The mean time from HR to initiation of treatment
      was 8 days for infection survivors and 13.3 days for infection-related deaths.
      Infectious mortality after HR remains significant. Contributing risk factors are
      advanced age, multiple comorbid conditions, and extent of HR. Ventilator
      dependence and delays in antibiotic therapy were associated with infectious
      mortality. Although gram-negative enteric infections were more common, abdominal,
      lung, and line infections with gram-positive cocci had higher associated
      mortality; especially when antibiotic resistant strains were present.

PMID- 15481296
TI  - Trauma in nonagenarians and centenarians: review of 137 consecutive patients.
AB  - The purpose of this study was to examine the hospital course and outcomes of
      elderly trauma patients. We accomplished a retrospective review of all
      consecutive trauma patients admitted to a level II trauma center from January
      2000 to April 2002. Gender, Injury Severity Score (ISS), length of stay (LOS),
      operative procedure, morbidity, and mortality of patients > or = 90 years of age
      were compared with younger patients. Of 2645 trauma admissions, 137 patients (5%)
      were > or = 90 years (range, 90 to 108 years; mean, 93.1 years); 5 patients were
      > or = 100 years. One hundred eleven (81%) patients were female; 26 (19%) male.
      Average ISS for patients > or = 90 was 8.75 and was 7.78 for younger patients.
      One hundred sixteen elderly patients (85%) had ISS < 15. Falls were the most
      common mechanism of injury (93%), usually ground-level falls (64%). Two hundred
      ninety-two injuries included 133 fractures and 102 soft tissue injuries. Thirty
      four elderly patients (25%) and 733 younger patients (29%) required surgery.
      Complications developed in 8 per cent of older and 6 per cent of younger
      patients. Hospital LOS averaged 4.36 days for older and 3.51 days for younger
      patients. Six older (4.4%) and 63 younger (2.5%) patients died. ISS scores and
      LOS were slightly higher in elderly patients, but morbidity and mortality were
      comparable in both groups.

PMID- 15481298
TI  - Management of blunt splenic injury in patients with concurrent infectious
      mononucleosis.
AB  - Selective nonoperative management is appropriate for most blunt splenic injuries
      in adults and children, but the efficacy of this approach is unknown when injury
      occurs in patients with concurrent infectious mononucleosis. We have reviewed our
      experience during the past 23 years with the selective nonoperative management of
      blunt splenic injury in these patients. Medical record review identified nine
      patients with blunt splenic injury and infectious mononucleosis from 1978 to
      2001, representing 3.3 per cent of our total trauma population with blunt splenic
      injury treated during that interval. Two patients underwent immediate splenectomy
      because of hemodynamic instability. Seven patients were admitted with the intent
      to treat nonoperatively. Five patients were successfully managed nonoperatively.
      Two patients failed nonoperative management and underwent splenectomy, one
      because of hemodynamic instability and one because of an infected splenic
      hematoma. Concurrent infectious mononucleosis does not preclude the successful
      nonoperative management of blunt splenic injury. This small subset of patients
      may be managed nonoperatively using the same criteria as for patients whose
      splenic injuries are not complicated by infectious mononucleosis.

PMID- 15481297
TI  - Regulation of tumor necrosis factor-alpha production in the isolated rat heart
      stimulated by bacterial lipopolysaccharide or reactive oxygen.
AB  - Reperfusion after cardiopulmonary bypass causes induction of reactive oxygen
      species (ROS), elevated plasma levels of bacterial lipopolysaccharide (LPS), and
      production of tumor necrosis factor-alpha (TNF) by the heart. Nuclear factor
      kappaB (NF-kappaB) regulates the expression of TNF. Because NF-kappaB is
      activated by both LPS and ROS, we hypothesized that an inhibitor of NF-kappaB,
      pyrrolidine dithiocarbamate (PDTC), would block release of TNF from the heart
      stimulated by these two agents. With Institutional animal care and use committee
      (IACUC) approval, rat hearts were perfused Langendorf style. LPS was infused and
      ROS were generated with a hypoxanthine/xanthine oxidase system. PDTC was added to
      the perfusion buffer. Other hearts were treated with forskolin in order to
      elevate cyclic AMP. Timed collections of coronary effluent were made for the
      determination of coronary flow and measurement of TNF. LPS stimulated TNF release
      to a maximum of 2247 +/- 133 pg/min at 150 minutes. PDTC inhibited LPS-stimulated
      TNF release. For instance, at 150 minutes, LPS-stimulated TNF release was 449 +/-
      49 pg/min with 100 microM PDTC and was 70 +/- 65 pg/mL with 250 microM PDTC (P <
      0.05 vs LPS alone). ROS stimulated TNF release was 1494 +/- 130 pg/min at 150
      minutes and was not affected by PDTC. Forskolin almost completely blocked TNF
      release stimulated by LPS or ROS. These data are consistent with the notion that
      inhibitors of NF-kappaB block cytokine production stimulated by some agents but
      not others.

PMID- 15481299
TI  - Predictors of mortality in trauma patients.
AB  - The purpose of this study was to ascertain risk factors for death from trauma.
      The large cohort allows for simultaneous evaluation of known mortality risk
      factors along with controlling for factors to assess the influence of each
      independently. Individually, base deficit, temperature, hypotension, age, and
      injury severity have been shown to be associated with an increased risk of death.
      However, in the English literature, there is no data on the independent
      predictive power and interaction of these risk factors. A review of trauma
      registry parameters from 1995 to 2000 was used. Demographics, injury severity,
      physiological and hematological parameters, and time data were evaluated in a
      univariate analysis. Variables significantly associated with mortality were
      entered into a stepwise backward multiple logistic regression. There were 1276
      deaths (8.9%) with 25 per cent of the deaths within 3 hours. The top four
      predictors of mortality in this group were partial thromboplastin time (OR 3.37,
      95% CI: 2.51-4.52), positive head computed tomography result (OR, 2.47; 95% CI,
      1.95-3.04), initial hemoglobin (OR, 1.69; 95% CI, 1.23-2.31), base deficit (OR,
      1.62; 95% CI, 1.29-2.04), and trauma resuscitation bay systolic blood pressure
      (OR, 1.45; 95% CI, 1.11-1.88). We conclude that prognostic indicators of all
      cause mortality after trauma, which remain independent in the presence of all
      other factors and are potentially treatable, included low hemoglobin, elevated
      prothrombin and partial thromboplastin time, low scene and trauma bay systolic
      pressure, and elevated base deficit. The independent indicators of mortality,
      which are untreatable, included head injury, increasing age, and Injury Severity
      Score.

PMID- 15481300
TI  - Impact of self-reported physical activity participation on proportion of excess
      weight loss and BMI among gastric bypass surgery patients.
AB  - Habitual physical activity is an important component of successful weight loss
      programs for morbidly obese individuals. This study examined self-reported
      physical activity (PA) participation in relation to excess weight loss and body
      mass index (BMI) reduction among gastric bypass surgery patients (GBS). PA
      participation was hypothesized to contribute to both greater excess weight loss
      (% EWL) and a greater reduction in BMI at 2 years postsurgery. PA participation
      was measured via self-report among 1585 GBS patients between 1988 and 2001. GBS
      patients were assigned to groups [PA (n = 1479)/no PA (n = 106)] and further
      stratified by presurgical BMI [35-49 kg/m2 (n = 897) and 50-70 kg/m2 (n = 688)].
      Findings showed that GBS patients who reported PA participation were younger [P <
      0.0001, PA (40.1 +/- 9.9) vs no PA (44.2 +/- 11.2)], had greater % EWL [P =
      0.0081, PA (68.2 +/- 17.4%) vs no PA (63.9 +/- 19.5%)], and a greater decrease in
      BMI [P = 0.0011, PA (18.3 +/- 5.7 kg/m2) vs no PA (16.6 +/- 5.4 kg/m2)]. When
      stratified by presurgical BMI, only physically active patients with a BMI of 50
      70 kg/m2 showed an increase in % EWL [P = 0.0444, PA (63.2 +/- 16.5) vs no PA
      (57.9 +/- 17.3)], whereas both BMI groups showed significant reductions in BMI at
      2 years [BMI of 35-49 kg/m2 P = 0.0184, PA (16.0 +/- 4.0 kg/m2) vs no PA (14.4 +/
      4.0 kg/m2); and BMI of 50-70 kg/m2 P = 0.0221, PA (21.50 +/- 6.0 kg/m2) vs no PA
      (19.7 +/- 5.5 kg/m2)], respectively. PA had a favorable effect on % EWL and BMI
      among GBS patients at 2 years postsurgery, thus supporting the inclusion of
      habitual PA in a comprehensive GBS postsurgical weight maintenance program.

PMID- 15481301
TI  - Cholecystectomy and acquired factor VIII inhibitor coagulopathy.
AB  - The purpose of this study was to describe the outcome of patients undergoing
      surgery with recognized and unrecognized factor VIII inhibitor. The setting was a
      tertiary care center with a community-based general surgery training program. Two
      patients with acquired factor VIII inhibitor coagulopathy required
      cholecystectomy. Interventions included intravenous immunoglobulin (IVIG) and
      factor VIII transfusions. An elderly patient undergoing urgent open
      cholecystectomy for acute cholecystitis exsanguinated despite postoperative
      recognition and treatment of factor VIII inhibitor. A second patient with known
      factor VIII inhibitor underwent laparoscopic cholecystectomy with perioperative
      transfusions of factor VIII and IVIG. No hemorrhage occurred, but cost to the
      patient exceeded 50,000 dollars. Acquired factor VIII inhibitor coagulopathy is
      rare and potentially lethal. Preoperative recognition and appropriate hematologic
      intervention is crucial to achieve a successful outcome.

PMID- 15481302
TI  - Breast conservation therapy for invasive lobular carcinoma: the impact of lobular
      carcinoma in situ in the surgical specimen on local recurrence and axillary node
      status.
AB  - Forty patients undergoing breast-conserving therapy for invasive lobular
      carcinoma were studied for the volume of lobular carcinoma in situ (LCIS) in the
      surgical specimen and its relationship to the surgical margins. The pathology of
      all cases was reviewed for margin status as well as the volume of LCIS in the
      surgical specimen. Mean follow-up time was 67 months. There were no local
      recurrences despite the fact that 38 per cent of patients had close or involved
      margins. There was one cancer-related death. Increasing tumor size and moderate
      or extensive involvement of the surgical specimen with LCIS were found to be
      independent predictors of axillary node metastases. The volume of LCIS in the
      surgical did not appear to have an impact on local recurrence. This paper adds to
      the growing body of literature suggesting that in patients undergoing breast
      conserving therapy, LCIS in the surgical margin does not impact the risk of local
      recurrence and therefore may not require reexcision for close or involved
      surgical margins.

PMID- 15481303
TI  - A retrospective study of nosocomial pneumonia in postoperative patients shows a
      higher mortality rate in patients receiving nasogastric tube feeding.
AB  - Pneumonia remains a significant cause of morbidity and mortality in surgical
      patients. Though most studies have focused on pneumonia in trauma or special
      respiratory intensive care units (ICU), we examine postoperative ventilator
      associated pneumonia in patients undergoing elective operations. We hypothesized
      that a study of multiple clinical variables would disclose factors influencing
      morbidity and mortality in these patients. We conducted a retrospective review of
      1969 patients who underwent elective general, cardiac, and general thoracic
      procedures during a 6-month period in a private teaching hospital. A total of 77
      patients (3.9%) developed postoperative ventilator-associated pneumonia. Thirty
      eight (49%) patients had a history of smoking and 27 (35%) had chronic
      obstructive pulmonary disease (COPD). Among these 77 patients, 20 (26%)
      experienced recurrent pneumonia. The overall mortality rate for patients
      developing pneumonia was 34 per cent. At diagnosis of pneumonia, 33 patients were
      receiving enteral nutrition through nasogastric feeding tubes, whereas 41
      received no enteral feeding. The method of nutritional intake was not known in 3
      patients. The feeding/nonfeeding groups were similar in age and underlying
      disease, differing significantly only in the higher number of smokers in the
      patients not receiving enteral nutrition (P = 0.03). To our surprise, the
      mortality rate from all causes was higher (P = 0.018) in the patients who
      received tube feedings through soft, nasogastric feedings (33%) than in those not
      enterally fed (17%). Parenteral nutrition, COPD, number of ventilator days, and
      the location of the tip of the feeding tube did not correlate with mortality. The
      mortality rate from all causes was higher in patients with postoperative
      pneumonia who received tube feedings, despite similar underlying medical
      illnesses. Enteral feeding of postoperative surgical patients has many desirable
      effects, but prospective studies should address harmful effects, such as presumed
      aspiration and related pneumonia.

PMID- 15481304
TI  - Abdominal wall necrotizing fasciitis from dislodged percutaneous endoscopic
      gastrostomy tubes: a case series.
AB  - We report three cases of abdominal wall necrotizing fasciitis that occurred as a
      result of leakage from displaced percutaneous endoscopic gastrostomy tubes. This
      is the first report of such a series. Patients underwent extensive operative
      excisions of their abdominal walls down to their posterior fascia. All patients
      tolerated their initial surgery, however, two patients ultimately expired from
      respiratory complications. The surviving patient underwent multiple repeat
      debridements and reconstructive abdominal wall surgery. We review the
      epidemiology of patients at risk for this complication and discuss its
      presentation, as well as the appropriate workup and management. We also address
      the issues of closure of large abdominal wall defects and future alimentation in
      this patient group. Finally, abdominal wall necrotizing faciitis from gastrostomy
      tube leakage is a devastating complication, and the development of preventative
      strategies for patients at risk is of paramount importance.

PMID- 15481306
TI  - Visceral aneurysm and vascular anomaly involving the splenic artery.

PMID- 15481307
TI  - Indocyanine green alters transepithelial electrical parameters of the distal
      colon.
AB  - Indocyanine green (ICG) is used as a dye marker of the vascular space in
      gastroenterology, ophthalmology, neurology, and critical care medicine. It is
      widely regarded to be inert. We report, however, that ICG demonstrates effects on
      colonic transepithelial electrical parameters which could form a basis for a
      growing number of deleterious gastrointestinal and other clinical effects. Short
      circuit current (Iscc), transepithelial conductance (gt), and transepithelial
      paracellular flux of 14C-D-mannitol were monitored across sheets of rat distal
      colon. Dye was introduced to mucosal or serosal tissue surfaces at a
      concentration similar to that used in vivo (10 microg/ml). ICG decreased Iscc by
      over 50% and gt by over 10%. Transepithelial mannitol flux was not altered. Dye
      was effective only from the serosal surface. Cyclic AMP-induced spiking of Iscc
      was not affected by ICG. Preincubation with amiloride or furosemide did not
      affect the action of the dye on gt or Iscc. ICG at in vivo dosages is clearly
      capable of inhibiting ion transport across colon epithelial tissue. The serosal
      site of action indicates activity on a basal-lateral transport system or
      diffusion into the cell only across the basal-lateral membrane followed by
      inhibition of a transporter from the intracellular side. ICG should not be
      considered inert in vivo. Leakage of ICG from the vascular space into the
      interstitial fluid space will likely result in tissue morbidity.

PMID- 15481308
TI  - Effect of ischemia-reperfusion on Na+, K+-ATPase expression in human liver tissue
      allograft: image analysis by confocal laser scanning microscopy.
AB  - We have analyzed the effect of ischemia-reperfusion on expression of hepatic
      Na+,K+-ATPase on bile canalicular (BCM) and basolateral membranes (BLM) in human
      liver allografts using confocal laser scanning microscopy imaging. Na+, K+
      ATPase, an integral membrane enzyme, plays a key role in the physiology and
      structure of hepatocytes, where it maintains the electrochemical gradients for
      Na+ and K+ across the cell membrane. The concentrations of these ions as well as
      their gradients regulate the active transport across the plasma membrane for bile
      acid and water from sinusoidal to canalicular membranes. In addition, Na+,K+
      ATPase is also involved in cellular structure because of its close relationship
      with submembrane microfilaments and its implication in tight junction assembly.
      Therefore, Na+,K+-ATPase appears as an indicator of tissue viability and hepatic
      functionality during liver transplantation. Its localization and its function in
      BCM are still controversial. As in previous studies, we found an enzyme
      expression in both BLM and BCM. We show that ischemia induced a decrease in
      Na+,K+-ATPase expression only in BCM. This result could be explained by the
      differences in biochemical membrane environment between basolateral and bile
      canalicular Na+,K+-ATPase. Membrane lipid fluidity, which is more elevated in BLM
      than in BCM, could protect the enzyme during ischemia. After reperfusion, Na+,K+
      ATPase expression was strongly decreased in both BCM and BLM. This alteration
      following reperfusion is probably due to multiple factors: direct alteration of
      the enzyme catalytic subunit and modification of its environment and membrane
      lipid fluidity by free radicals and changes in ATP levels and ionic distribution.
      This important decrease in Na+,K+-ATPase expression of both BLM and BCM could
      disturb not only hepatic secretory function but also cellular volume and
      structure during the postoperative period.

PMID- 15481305
TI  - Ischemia-reperfusion injury of the intestine and protective strategies against
      injury.
AB  - Ischemia-reperfusion injury of the intestine is a significant problem in
      abdominal aortic aneurysm surgery, small bowel transplantation, cardiopulmonary
      bypass, strangulated hernias, and neonatal necrotizing enterocolitis. It can also
      occur as a consequence of collapse of systemic circulation, as in hypovolemic and
      septic shock. It is associated with a high morbidity and mortality. This article
      is a comprehensive review of the current status of the molecular biology and the
      strategies to prevent ischemia-reperfusion injury of the intestine. Various
      treatment modalities have successfully been applied to attenuate reperfusion
      injury in animal models of reperfusion injury of the intestine. Ischemic
      preconditioning has been found to be the most promising strategy against
      reperfusion injury during the last few years, appearing to increase the tolerance
      of the intestine to reperfusion injury. Although ischemic preconditioning has
      been shown to be beneficial in the human heart and the liver, prospective
      controlled studies in humans involving ischemic preconditioning of the intestine
      are lacking. Research focused on the application of novel drugs that can mimic
      the effects of ischemic preconditioning to manipulate the cellular events during
      reperfusion injury of the intestine is required.

PMID- 15481310
TI  - Severe cholestatic hepatitis as the first symptom of secondary syphilis.

PMID- 15481309
TI  - Prostaglandin E2 inhibits platelet-derived growth factor-stimulated cell
      proliferation through a prostaglandin E receptor EP2 subtype in rat hepatic
      stellate cells.
AB  - Prostaglandin (PG) E2 inhibits hepatic stellate cell (HSC) mitogenesis. PGE
      specific receptors are divided into four subtypes that are coupled either to Ca2+
      mobilization (EP1 and EP3) or to the stimulation of adenyl cyclase (EP2 and EP4).
      The aims of the current study were to identify PGE receptor subtypes in cultured
      rat HSC and to examine which PGE receptor subtype(s) mediates the inhibitory
      effect of PGE2 on platelet-derived growth factor (PDGF)-stimulated proliferation.
      Reverse transcription-polymerase chain reaction analysis was performed to detect
      PGE receptor subtype mRNA expression. Cell proliferation was determined by
      measuring [3H]thymidine incorporation, and intracellular cyclic AMP was measured
      by radioimmunoassay. Cultured rat HSC expressed mRNAs for all four subtypes of
      PGE receptor. PGE2- and EP2-selective agonist produced dose-dependent inhibitory
      effects on PDGF-stimulated proliferation. Neither EP1-, EP3-, nor EP4-selective
      agonists showed any inhibitory effect. An adenylate cyclase inhibitor strongly
      blunted the inhibition of DNA synthesis elicited by PGE2 and the EP2 agonist. The
      EP2 agonist generated higher and more prolonged increases in intracellular cyclic
      AMP than the EP4 agonist. Activation of the PGE EP2 receptor has an
      antiproliferative effect in HSC that may be mediated by cyclic AMP-related signal
      transduction pathways.

PMID- 15481311
TI  - Analysis of pancreatic elastase-1 concentrations in duodenal aspirates from
      healthy subjects and patients with chronic pancreatitis.
AB  - Fecal pancreatic elastase 1 (PE-1) has been advocated as a noninvasive marker of
      pancreatic function and allows detection of moderate and severe exocrine
      insufficiency. Few studies have evaluated the utility of measuring PE-1 in
      duodenal fluid for the diagnosis of pancreatic insufficiency. Our purpose was (1)
      to determine the feasibility of measuring PE-1 concentrations in duodenal
      aspirates obtained through our endoscopic pancreatic function test (ePFT) in
      healthy subjects and patients with chronic pancreatitis (CP) and (2) to determine
      correlations between duodenal PE-1 concentrations and bicarbonate and lipase
      concentrations in duodenal fluid. Healthy subjects (HS) and CP patients underwent
      an ePFT with CCK or secretin. CP was defined as endoscopic retrograde
      pancreatography (ERP) Cambridge class III-IV, endoscopic ultrasound (EUS) score
      >5, or presence of pancreatic calcifications on CT scan. Duodenal fluid PE-1,
      lipase, and bicarbonate concentrations were measured in each study group.
      Duodenal lipase and bicarbonate concentrations were measured using an
      autoanalyzer (Roche Diagnostics, Indianapolis, IN). PE-1 was measured using an
      ELISA (Genova Diagnostics, Asheville, NC). Ten HS and 10 CP patients were
      studied. In the CCK test the median peak lipase for HS and CP was 1605 and 113
      IU/L, respectively (P < 0.008). In the secretin test the median peak bicarbonate
      for HS and CP was 102 and 40 mEq/L, respectively (p < 0.008). Median PE-1
      concentrations for HS and CP were 317 and 63 microg/ml, respectively, after CCK
      stimulation (p = 0.046) and 87 and 17 microg/ml, respectively, after secretin
      stimulation (p = 0.033). Statistically significant correlations were found
      between [PE-1] and peak [lipase] (r = 0.83, P < 0.001), as well as [PE-1] and
      peak [HCO3(3)-] (r = 0.65, P = 0.037). Conclusions are as follows: (1) PE-1
      concentrations can be measured from duodenal fluid obtained by endoscopic
      aspiration. (2) Duodenal fluid PE-1 concentrations are decreased in CP compared
      to HS. (3) Duodenal fluid [PE-1] has an excellent correlation with [lipase] and
      therefore is a marker of acinar cell function. (4) Secretin-stimulated endoscopic
      function testing with measurement of bicarbonate and PE-1 may provide a
      simultaneous assessment of both ductal cell and acinar cell function.

PMID- 15481312
TI  - Cyst formation of duodenal heterotopic pancreas accompanied by pancreas divisum.

PMID- 15481313
TI  - Electroacupuncture restores impaired gastric accommodation in vagotomized dogs.
AB  - The aim of this study was to investigate the effects of electroacupuncture (EA)
      on impaired gastric accommodation in a canine model. Ten dogs were chronically
      implanted with a gastric cannula in the stomach. Truncal vagotomy was performed
      in five of the dogs. A polyethylene bag attached at the end of a catheter was
      placed in the proximal stomach via the cannula. Gastric compliance, gastric tone,
      and postprandial gastric accommodation were evaluated using a gastric barostat
      with and without EA on two separate days, respectively. Results were as follows.
      (1) The postprandial gastric volume increase was 180.8 +/- 54.3 ml in vagotomized
      dogs, which was significantly lower than that (317.3 +/- 37.3 ml; P < 0.05) in
      normal dogs. (2) In normal dogs, EA did not affect gastric compliance, basal
      gastric tone, or postprandial gastric accommodation. (3) In vagotomized dogs, EA
      did not affect gastric compliance or basal gastric tone but restored the impaired
      gastric accommodation. The postprandial gastric volume increase was significantly
      enhanced with EA compared to the control (275.0 +/- 45.8 vs. 180.8 +/- 54.3 ml; P
      < 0.02). EA restores impaired gastric accommodation induced by vagotomy and may
      have therapeutic potential for patients with gastroparesis.

PMID- 15481314
TI  - Are Helicobacter species and enterotoxigenic Bacteroides fragilis involved in
      inflammatory bowel disease?
AB  - The aim of this study was to determine if either Helicobacter or enterotoxigenic
      Bacteroidesfragilis (ETBF) was linked to inflammatory bowel disease (IBD), using
      PCR. We analyzed the luminal washings and colonic biopsies of 35 patients with
      IBD and 37 control patients. The presence of Helicobacter was confirmed in the
      luminal washing of one IBD patient and three control patients and in the biopsies
      of two IBD patients. Ten of 28 control patients and 8 of 32 IBD patients had a
      positive luminal washing for the enterotoxin gene. Six of 33 control patients and
      4 of 32 IBD patients had positive biopsies. The prevalence of the enterotoxin
      gene was higher in IBD patients with active disease compared with patients with
      inactive disease, although it did not achieve statistical significance. In
      conclusion, Helicobacter was not associated with IBD in our population of
      patients, although ETBF may be associated with active disease.

PMID- 15481315
TI  - Decreased total and corrected antioxidant capacity in patients with inflammatory
      bowel disease.
AB  - Oxidative stress and depletion of antioxidants may play a key role in the
      pathogenesis of inflammatory bowel disease (IBD)-related intestinal damage. A new
      automated assay for the determination of blood total antioxidant capacity (TAC),
      based on the crocin bleaching method, has been used for the measurement of TAC
      and corrected TAC (cTAC) in patients with ulcerative colitis (UC) and Crohn's
      disease (CD) in comparison to healthy controls (HC). Ninety-four patients with
      UC, 97 patients with CD, and 72 HC were included in this study. Serum TAC was
      measured in all patients and controls on an Olympus AU-600 chemistry analyzer
      using a TAC kit. cTAC was calculated from TAC after subtraction of the
      interactions due to endogenous uric acid, bilirubin and albumin. Mean serum TAC
      as well as cTAC levels were significantly lower in both UC and CD patients
      compared with HC (P < 0.0001). Patients with active UC had no different TAC and
      cTAC compared to those with inactive disease. Patients with active CD had
      significantly lower mean TAC compared to those with inactive disease but cTAC was
      not different between the two phases of disease activity. Patients with proctitis
      had significantly higher TAC and cTAC compared to patients with left-sided
      colitis and total colitis. In CD patients no association between disease
      localization and these markers was found. TAC and cTAC are significantly reduced
      in IBD patients compared with controls irrespective of disease activity. The
      decreased antioxidant defenses may be a primary phenomenon severely compromising
      the mucosa and therefore increase susceptibility to oxidative tissue damage.

PMID- 15481316
TI  - Relationship between fecal calprotectin, intestinal inflammation, and peripheral
      blood neutrophils in patients with active ulcerative colitis.
AB  - Active ulcerative colitis (UC) is associated with elevated granulocytes and
      monocytes/macrophages (GM) which show activation behavior and increased survival
      time. Further, fecal calprotectin (a stable neutrophil protein) level parallels
      intestinal inflammation and can predict UC relapse. Since GM are major sources of
      inflammatory cytokines and chemokines, they are suspected to have roles in the
      initiation and perpetuation of UC. Our objective was to investigated
      relationships between peripheral blood (PB) neutrophils, calprotectin, and UC
      disease activity. Full PB and calprotectin were determined in 69 healthy controls
      and 31 patients with UC, then 7 randomly selected patients received GM adsorptive
      apheresis (GMA) with Adacolumn, 10 sessions of 60-min duration each. Patients
      with UC had higher neutrophil counts (P < 0.001), but lower lymphocyte counts (P
      < 0.001) compared with controls. Further, fecal calprotectin levels showed a
      correlation with UC clinical activity index (CAI; P < 0.001) and mucosal
      inflammation (P < 0.001). Following GMA, there were falls in neutrophils (P <
      0.02), CAI (P < 0.02) and calprotectin (P < 0.02). In conclusion, GM appear to
      contribute to intestinal inflammation and UC activity and reduction of these
      cells by GMA should benefit patients with active UC. Further, the correlations
      among calprotectin, UC activities, and PB neutrophils should serve as the basis
      for preemptive actions to control this disease.

PMID- 15481317
TI  - Ileal pouch-anal anastomosis, conventional ileostomy and ileorectal anastomosis
      modify cholesterol metabolism.
AB  - Proctocolectomy modifies the enterohepatic circulation and activity of bacterial
      enzymes depending on the structure of the stoma and function of the terminal
      ileum. We evaluated in our comparative study effects of different colectomy
      constructions on cholesterol metabolism. Levels of lipoprotein cholesterol and
      triglycerides, noncholesterol sterols, and squalene in serum, fecal fat, and bile
      acids, cholesterol absorption efficiency, and cholesterol metabolism by sterol
      balance technique were analyzed in human subjects with ileal pouch-anal
      anastomosis (n = 34), conventional ileostomy (n = 8), ileorectostomy (n = 6), and
      controls (n = 29). Malabsorption of bile acids, but not of fat, and low serum
      levels of total and low-density lipoprotein cholesterol, but high levels of high
      density lipoprotein cholesterol and increased cholesterol synthesis were evident
      in the colectomy groups. In contrast to the ileorectostomy group, expressing high
      absorption and biliary secretion of cholesterol, a low cholesterol absorption
      percentage accompanied by elevated serum proportions of cholesterol precursor
      sterols and phytosterols characterized the ileal pouch-anal anastomosis and
      conventional ileostomy groups. After colectomy, fecal excretion of secondary bile
      acids was low, whereas relative proportions of identifiable bile acids remained
      the same in each study group. Low serum levels of total and low-density
      lipoprotein cholesterol of colectomized subjects may decrease the risk of
      premature atherosclerosis. The favorable serum lipid profile was due to enhanced
      fecal loss of cholesterol as bile acids despite abnormally high cholesterol
      synthesis. Ileal dysfunction probably diminished cholesterol absorption in
      subjects with ileal pouch-anal anastomosis and conventional ileostomy, with no
      explanation for those with ileorectostomy with no clinical gastrointestinal
      dysfunction. Relative synthesis of identifiable primary bile acids remained
      unchanged postoperatively, but formation of secondary bile acids was weak due to
      scarce bacterial flora.

PMID- 15481318
TI  - Treatment of pyoderma gangrenosum with infliximab in Crohn's disease.
AB  - Pyoderma gangrenosum (PG) is an ulcerating noninfectious disease of the skin seen
      in 1 to 5% of patients with inflammatory bowel disease. The pathogenesis of PG
      has yet to be determined but may be related to abnormal T cell responses and the
      production of TNF-alpha, a powerful proinflammatory cytokine. Infliximab, a
      chimeric monoclonal antibody to TNF-alpha, has been approved for the treatment of
      Crohn's disease. We present four patients with PG treated with Infliximab for
      fistulizing Crohn's in whom complete healing of PG was achieved. Four patients
      with active fistulizing Crohn's disease and PG were treated. All patients were
      females ranging in age from 48 to 60 years, with a mean age of 54 years. Three of
      four patients had PG lesions located on the lower extremities; one patient had
      peristomal disease. All patients had at least colonic involvement of their
      Crohn's. The patients received either a single infusion or a series of three 5
      mg/kg Infliximab infusions. All four patients demonstrated rapid healing of PG
      within 4 weeks of the first infusion of Infliximab. PG healing followed
      improvement in bowel disease. Complete resolution without recurrence was noted in
      all patients. Rapid resolution of PG was noted in four female patients with
      fistulizing Crohn's disease treated with Infliximab. Healing was complete,
      without recurrence. The anti-TNF-alpha properties of Infliximab suggest that
      healing may be mediated by the drug's effect on cytokine pathways, perhaps by
      blunted T cell activation early in the inflammatory cascade. We suggest an
      independent effect of Infliximab on PG.

PMID- 15481319
TI  - Pneumocystis carinii pneumonia with oral candidiasis after infliximab therapy for
      Crohn's disease.

PMID- 15481320
TI  - Meningitis and epidural abscess associated with fistulizing Crohn's disease.

PMID- 15481321
TI  - Protective effect of lactulose on dextran sulfate sodium-induced colonic
      inflammation in rats.
AB  - Promising results have recently been obtained with pre- and probiotic therapy in
      ulcerative colitis (UC). The prebiotic potential of lactulose is well
      established, but it has not yet been investigated in experimental colitis models.
      The purpose of the study was to examine the effect of lactulose on an UC model
      induced by 3% dextran sulfate sodium (DSS) solution added to drinking water for 7
      days in male Wistar rats. Lactulose (300-1000 mg/kg) or 5-aminosalicylic acid (5
      ASA; 150 mg/kg) was administered orally twice daily for 6 days. Colonic
      ulceration area, colon length, body weight changes, diarrhea/bloody feces,
      colonic mucosal myeloperoxidase activity (MPO), thiobarbituric acid reactive
      substances (TBARS), and histology were examined. Treatment of animals with DSS
      for 7 days resulted in severe colonic lesions accompanied by diarrhea, bloody
      feces, a decrese in body weight, shortening of the colon length, and an increase
      in MPO activity as well as TBARS, compared to normal rats. Lactulose treatment
      ameliorated DSS-induced colitis in a dose-dependent manner, and at 1000 mg/kg all
      of the parameters examined, except TBARS, were shown to improve significantly as
      compared to controls. Daily administration of 5-ASA also significantly reduced
      the severity of colonic lesions following DSS treatment. These results
      demonstrated the protective effect of lactulose in this rat colitis model and
      suggested that the background of this lactulose effect may be due to alterations
      of colonic microflora.

PMID- 15481322
TI  - Proabsorptive action of gum arabic in isotonic solutions orally administered to
      rats. II. Effects on solutes under normal and secretory conditions.
AB  - Gum arabic (GA) is a natural proteoglycan with proabsorptive capacity
      attributable to its physico-chemical properties. Previous experiments showed that
      in rats oral administration of GA in an isotonic solution had a generally
      positive effect. This study extends the investigation to include acetaminophen
      and to evaluate whether GA could also act under secretory conditions induced by
      theophylline. Test solutions were orally administered to rats under CO2
      anesthesia and blood concentrations followed for 3 hr. The secretory effects of
      theophylline were clearly observed for sodium and zinc. Addition of GA resulted
      in a more rapid rate of glutamate absorption, under normal physiologic
      conditions, as indicated by the higher area under the curve (AUC). There were no
      differences in the presence of theophylline. Acetaminophen blood concentrations
      peaked about 30 min after administration, and the AUC in rats that received GA
      was higher than in those that got the solution without GA. AUCs for total body
      water distribution with time and those for glucose concentrations were
      indistinguishable whether the solutions contained or did not contain either GA or
      theophylline. The results confirm that oral administration of GA can accelerate
      absorption of some solutes, including pharmacologic agents.

PMID- 15481323
TI  - Screening of tissue transglutaminase antibody in healthy blood donors for celiac
      disease screening in the Turkish population.
AB  - Celiac disease (CD) is a disease having the characteristic pathology of the
      mucosa of the small intestine. The prevalence of CD in the Turkish population has
      not been investigated previously. The present study was designed to determine the
      prevalence of CD in healthy blood donors. Serum samples of 2000 healthy blood
      donors presenting to Hacettepe University Faculty of Medicine Hospital Blood Bank
      were tested for tissue transglutaminase (tTG) IgA and IgG antibodies with enzyme
      linked immunosorbent assay (ELISA; Euroimmune, Germany). The histopathological
      findings for the cases with positive serology were evaluated. The distribution of
      sex was 95.7% male, and 4.3% female. The mean age was 33 +/- 9. Among 2000
      donors, 23 (1.15%) were positive for tTG IgA antibody and 3 (0.15%) were positive
      for tTG IgG antibody. None of the samples was positive for both antibodies. Serum
      total IgA was measured in two cases with only tTG IgG positivity and was found to
      be low in one case. Twelve subjects positive for tTG agreed to endoscopy and
      biopsy. Histopathological examination revealed changes classified as Marsh III-II
      in one, Marsh II in two, Marsh I in seven, and Marsh 0 in two donors. This was
      the first study conducted to determine the prevalence of tTG positivity in the
      Turkish population. The tTG antibody positivity prevalence in healthy blood
      donors was as high as 1.3%. This study shows that the prevalence of CD in the
      Turkish population is relatively high in comparison to that in the Western world.

PMID- 15481324
TI  - Intestinal obstruction in celiac disease: case report.

PMID- 15481325
TI  - Celiac disease and chronic urticaria resolution: a case report.

PMID- 15481326
TI  - A rare case of "giant" right-sided retroperitoneal bronchogenic cyst.

PMID- 15481327
TI  - Growth hormone receptor expression in human colorectal cancer.
AB  - The purpose of this study was to determine whether human colorectal cancer (CRC)
      expresses growth hormone receptor (GHR) and whether growth hormone plays an
      important role in the development and progression of human CRC. We investigated
      42 specimens of CRC and normal colorectal mucous membrane, taken from the colon
      or rectum in a group of patients with CRC. Immunohistochemistry and reverse
      transcription-polymerase chain reaction (RT-PCR) technique were used to
      demonstrate GHR expression. The relationship between expression of GHR and
      clinical or pathological factors was analyzed. Immunohistochemical analyses
      revealed that GHR was expressed in human CRC (35/42; 83.33%) and appeared to be
      up-regulated compared to normal mucous tissue (29/42; 69.05%; P < 0.001).
      Contrasting sharply with the mostly strongly positive tumors, corresponding
      normal colorectal mucous membrane was negative or weakly positive. A significant
      inverse correlation was found between GHR expression and tumor stage (P = 0.002)
      and tumor differentiation (P = 0.036). In RT-PCR, 33 of the 42 tumors expressed
      GHR mRNA, while only 22 of the 42 normal colorectal mucous membranes did so. Our
      data demonstrate that GHR is frequently expressed in human CRCs and appears to be
      up-regulated compared to normal mucous tissue, thus supporting a possible role
      for growth hormone in CRC physiology.

PMID- 15481328
TI  - Spontaneously significant pneumoretroperitoneum misinterpreted as herniated
      intervertebral disc: an unusual presentation of perforation of ascending colon
      cancer.

PMID- 15481329
TI  - Increased hTR expression during transition from adenoma to carcinoma is not
      associated with promoter methylation.
AB  - Human telomerase RNA component (hTR) expression, which increases in the majority
      of cancer cells with an acquisition of telomerase activity, was concomitantly
      evaluated with methylation status and human telomerase reverse transcriptase
      (hTERT) expression in colorectal cancers and precursor lesions. hTR and hTERT
      expressions were detected by in situ hybridization and reverse transcription
      following polymerase chain reaction, respectively, in 15 colonic adenomas, 19
      sporadic colonic cancers at various histological stages, and 3 normal colonic
      mucosa samples. The methylationstatus of hTR was evaluated by methylation
      specific polymerase chain reaction following restriction endonuclease digestion
      and direct sequencing. hTERT expression was detected in 16 of 19 cancers. hTR
      expression was detected in all cancers including two cases of intramucosal
      carcinoma. No hTR signals were detected in the normal epithelium or in the
      adenomas with severe atypism. CpG dinucleotides in the 5'-untranslated region of
      hTR were completely unmethylated from -204 to -3 and mosaically methylated from 
      290 to -272, irrespective of the atypism. These results suggest that hTR
      expression is increased at the adenoma-to-carcinoma transition stage but is not
      always associated with hTERT expression. Hypomethylation of the hTR promoter
      region is not likely to be the main mechanism regulating hTR expression.

PMID- 15481330
TI  - Unusual presentation and diagnosis of extraintestinal follicular lymphoma.

PMID- 15481331
TI  - Aspirin-induced mucosal cell death in human gastric cells: evidence supporting an
      apoptotic mechanism.
AB  - This study was undertaken to define the role that apoptosis may play in inducing
      cellular injury and death in gastric mucosa exposed to aspirin. Apoptosis was
      characterized by DNA gel electrophoresis, terminal deoxynucleotidyl transferase
      dUTP nick-end labeling assay, and DNA-histone-associated complex formation. A
      human gastric cell line (AGS) was exposed to physiologic concentrations (3 to 50
      mM) of aspirin. Both time- and concentration-dependent effects on apoptosis were
      noted, which were effectively prevented by the caspase inhibitor z-VAD-fmk.
      Accordingly, the role of caspases in aspirin-induced apoptosis was also
      evaluated. Early activation of caspase-8 and caspase-9 was demonstrated,
      indicating a role for both receptor and mitochondrial pathways, respectively, in
      the apoptotic process. Corresponding activation of effector caspases-3, -6, and 
      7 was also evident, as was cleavage of PARP. We conclude that physiologically
      relevant concentrations of aspirin induces apoptosis in human gastric cells
      through a caspase-mediated mechanism.

PMID- 15481332
TI  - Structural signaling regulates inflammation-induced enhanced restitution and
      increased Mib-1 and Bax-indexes after superficial injury in isolated guinea pig
      gastric mucosa.
AB  - Several growth factors and cytokines are involved in regulation of the immediate
      repair of gastrointestinal mucosa, a process also called restitution. Few data
      exist on the effect of inflammation on this process using an explant model, where
      the folded basal lamina is included. The aim of the present study was to
      investigate the effect of simulated inflammation on restitution and on
      concomitant proliferation and apoptosis in isolated guinea pig gastric mucosa.
      Paired gastric mucosae were mounted in Ussing chambers (37 degrees C) and a
      superficial injury was induced (1.25 M NaCl/5 min) followed by a 4-hr restitution
      (pH 7.3-7.5). During perfusion, simulated inflammation was induced (with 0.5 or
      5.0 ng/ml IL-1beta or with activated polymorphonuclear [PMN] cells). The PI
      (proliferative index) and AI (apoptotic index) are expressed as the number of Mib
      1- or Bax-immunopositive cells per 300 foveolar cells, respectively. The mean
      recovery of electrophysiological resistance of tissues (R) after injury and
      exposure to serosal IL-1beta during restitution was 95.2 +/- 5.3% (mean +/- SD),
      whereas the value for control tissues was 89.6 +/- 6.9% (P = 0.016; N = 9). The
      mean recovery of R in tissues exposured to activated serosal PMN cells during
      restitution was 97.6 +/- 2.7%, whereas the value for unexposed control tissues
      was 93.8 +/- 2.9 (P = 0.004; N = 9). The enhancing effect of PMN cells was
      partially eliminated by serosal anti-ICAM, whereas serosal cytochalasin D
      abolished the process completely. The PI of tissues exposed to serosal PMN cells
      was 34.6 +/- 17.3, whereas the value for unexposed controls was 24.7 +/- 15.5 (P
      = 0.04; N = 5). The corresponding AI values were 17.0 +/- 2.8 and 12.0 +/- 5.7,
      respectively (NS; N = 4). Simulated inflammation either with serosal IL-1beta or
      with activated PMN cells enhances restitution and proliferation, whereas their
      effect on AI is only suggestive. Exogenous serosal anti-ICAM modulates
      restitution, whereas cytochalasin D abolishes it completely, suggesting that the
      structural signaling system including focal adhesions and cytoskeleton plays a
      significant role in the regulation of restitution.

PMID- 15481333
TI  - Pepsinogen secretion in cholecystokinin-1 receptor-deficient rats.
AB  - We examined the roles of cholecystokinin (CCK)-2 receptors in the regulation of
      pepsinogen secretion in the CCK-1 receptor deficient Otsuka Long-Evans Tokushima
      Fatty (OLETF) rats. Pepsinogen secretion was determined in fasted acute fistula
      OLETF and control Long-Evans Tokusima Otsuka (LETO) rats. Pepsinogen secretion in
      OLETF rats under basal conditions as well as in response to CCK-8 stimulation was
      significantly higher than that in LETO rats. CCK-1 receptor specific agonist ARL
      15849 was unable to stimulate pepsinogen secretion in OLETF rats, whereas it
      elicited pepsinogen secretion in LETO rats to levels similar to those obtained
      with equimolar CCK-8 stimulation. CCK-2 receptor antagonist reduced basal
      pepsinogen secretion and completely abolished CCK-8-stimulated pepsinogen output
      in OLETF rats, whereas in LETO rats, it reduced basal pepsinogen secretion but
      augmented CCK-8-stimulated pepsinogen output. CCK-1 receptor antagonist
      loxiglumide also greatly decreased CCK-8-stimulated pepsinogen secretion in OLETF
      rat, which indicates that loxiglumide is not a specific CCK-1 receptor
      antagonist. Intravenous infusion of somatostatin antagonist significantly
      increased CCK-8-stimulated pepsinogen secretion in LETO rats, whereas it had no
      significant influence on CCK-8-stimulated pepsinogen secretion in OLETF rats.
      These results indicate that CCK-8 stimulates pepsinogen secretion via CCK-2
      receptors in CCK-1 receptor deficient OLETF rats and that the higher CCK-8
      stimulated as well as basal pepsinogen secretion in OLETF rats might result from
      an elimination of tonic inhibition by somatostatin that is released from D cells
      through mainly CCK-1 receptors.

PMID- 15481334
TI  - Effect of ibuprofen on cyclooxygenase and nitric oxide synthase of gastric
      mucosa: correlation with endoscopic lesions and adverse reactions.
AB  - The aim of this study was to evaluate the effect of ibuprofen on gastric mucosa
      and enzymes involved in gastroprotection in healthy volunteers. Twenty-four
      Helicobacter pylori-negative subjects were randomized to treatment with ibuprofen
      or ibuprofen-arginate (each 600 mg/6 hr during 3 days). Endoscopies were
      performed 1 week before and after treatment. Biopsies were taken from the gastric
      antrum and corpus for determination of prostaglandin E2 (PGE2) by ELISA and
      cyclooxygenase (COX-1 and COX-2) and nitric oxide synthase (eNOS and iNOS) by
      western blot. All subjects had at least one gastric lesion except for two
      individuals taking ibuprofen-arginate. Ibuprofen-arginate caused a lower rate of
      clinical adverse reactions than ibuprofen. Subjects with gastric lesions or
      adverse reactions had lower PGE2 levels. COX-1, COX-2, eNOS, and iNOS were
      detectable in all subjects. The constitutive enzymes (COX-1 and eNOS) did not
      change after treatment. COX-2 was higher in corpus than antrum and it increased
      after ibuprofen treatment. iNOS tended to increase mildly in the corpus in
      subjects with adverse reactions or endoscopic lesions. There were no significant
      differences between ibuprofen and ibuprofen-arginate in PGE2, or enzymes.

PMID- 15481335
TI  - A functional polymorphism in the interleukin-1 receptor-1 gene is associated with
      increased risk of Helicobacter pylori infection but not with gastric cancer.
AB  - The proinflammatory cytokine interleukin-1 has been implicated in host
      susceptibility to Helicobacter pylori-associated disease. Recent studies suggest
      that this susceptibility may be under genetic control. It remains to be
      determined whether the relationship between IL-1 gene polymorphism and
      gastrointestinal disease in patients with H. pylori infection is due to the role
      of IL-1 in determining susceptibility to H. pylori infection per se or to the
      development of distinct pathological lesions. The aim of this study was to
      prospectively investigate the relationship between selected polymorphisms in
      three of the major IL-1 gene family members, seeking associations with H. pylori
      infection and/or gastric cancer. A total of 559 individuals were studied: 191
      patients attending for gastroscopy, 98 with current or previous H. pylori, an
      additional 79 patients with gastric cancer, and 289 healthy controls. The major
      novel finding of the study was a marked difference in the genotype frequencies
      for the IL1R1 Hinfl SNP in those with current or previous evidence of H. pylori
      compared to those without. (GG, 53 vs 75%; GA, 40 vs 19%; AA, 7 vs 6%; P =
      0.0079). The association indicates an increased risk of H. pylori infection or
      persistence in those with the IL1R1 Hinfl A allele (0.27 vs 0.156; P = 0.009; OR
      = 2.01). Our results suggest that the relationship among IL-1 gene polymorphism,
      H. pylori, and disease is more complex than initially proposed. More detailed
      studies of the IL-1 gene cluster are needed.

PMID- 15481336
TI  - The Helicobacter pylori restriction endonuclease-replacing gene, hrgA, and
      clinical outcome: comparison of East Asia and Western countries.
AB  - It has been suggested that the putative Helicobacter pylori virulence factor hrgA
      is the first disease-specific marker for an H. pylori-related disease, (i.e.,
      development of gastric cancer in East Asia). Our aim was to test the hypothesis
      that the presence of hrgA has disease specificity. We examined 458 H. pylori
      isolates including 289 from East Asia and 169 from Western countries whose cagA
      and vacA genotypes had previously been characterized. hrgA/hpyIIIR status and
      iceA genotypes were determined by polymerase chain reaction using DNA expanded
      from a single colony. hrgA was present in 29% of gastric cancers, 29% of ulcers,
      and 31% of gastritis cases among H. pylori from East Asia (P > 0.9). Overall,
      there was no significant relationship between the presence of the hrgA gene and
      disease presentation (cancer, ulcer, or neither) or between its presence and the
      cag pathogenicity island, vacA s1 , babA2, and oipA, "on" genotypes. The
      prevalence of the hrgA gene was significantly lower in H. pylori from East Asia
      (29%) vs. those from the West (49%) (P < 0.001). The prevalence of the hrgA gene
      was not related to clinical outcome or to other important putative virulence
      factors.

PMID- 15481337
TI  - Esophageal intramural pseudodiverticulosis: a case of a young woman.

PMID- 15481338
TI  - Meal-induced dysphagia and otalgia secondary to a pyriform sinus fistula.

PMID- 15481339
TI  - Hepatitis B: epidemiology and natural history.
AB  - Chronic infection with hepatitis B and its sequelae remains a major global health
      concern. Despite recommendations and implementation of vaccination programs, the
      health and economic burdens are still significant. People in endemic areas and
      immigrants from these areas need to be adequately screened and treated. HBeAg
      negative chronic hepatitis is increasingly recognized with additional challenges
      in management. Programs implementing primary prophylaxis strategies such as
      vaccination of high-risk adult and adolescent groups should continue.

PMID- 15481340
TI  - Serologic and molecular diagnosis of hepatitis B virus.
AB  - Serologic assays for HBV are the mainstay diagnostic tools for HBV infection.
      However, the advent of molecular biology-based techniques has added a new
      dimension to the diagnosis and treatment of patients with chronic HBV infection.
      Over the past decade, improvements in molecular technology, permitting detection
      of as few as 10 copies/mL of HBV DNA in serum have led to redefinitions of
      chronic HBV infection, as well as thresholds for antiviral treatment. As the
      sensitivity of these molecular techniques continues to improve, the challenge
      will be to standardize these assays as well as define clinically significant
      levels of HBV replication.

PMID- 15481341
TI  - Hepatitis B vaccines.
AB  - Immunization is the most effective way to prevent transmission of HBV and, hence,
      the development of acute or chronic hepatitis B. The national strategy to
      eliminate transmission of the virus in the United States includes vaccination of
      all newborn infants, children, adolescents, and high-risk adults. Postexposure
      prophylaxis is also advocated, depending on the vaccination and anti-HBs status
      of the exposed person. Seroprotection after vaccination, defined as anti-HBs > or
      = 10 mIU/mL, is achieved in over 95% of all vaccinees. The hepatitis B vaccines
      are very well tolerated with usually minimal adverse effects. Predictors of non
      response include increasing age, male gender, obesity, tobacco smoking, and
      immunocompromising chronic disease. For those who remain nonresponders after the
      second series of vaccination, adjuvants such as GM-CSF may be considered, but
      their results are variable.

PMID- 15481342
TI  - Hepatitis B virus: pathogenesis, viral intermediates, and viral replication.
AB  - Although HBV has the potential to generate an almost limitless spectrum of
      quasispecies during chronic infection, the viability of the majority of these
      quasispecies is almost certainly impaired due to constraints imposed by the
      remarkably compact organization of the HBV genome. On the other hand, single
      mutations may affect more than one gene and result in complex and unpredictable
      effects on viral phenotype. Better understanding of the constraints imposed by
      gene overlap and of genotype-phenotype relationships should help in the
      development of improved antiviral strategies and management approaches. Although
      the probability of developing viral resistance is directly proportional to the
      intensity of selection pressure and the diversity of quasispecies, potent
      inhibition of HBV replication should be able to prevent development of drug
      resistance because mutagenesis is replication dependent. If viral replication can
      be suppressed for a sufficient length of time, viral load should decline to a
      point where the continued production of quasispecies with the potential to resist
      new drug treatments no longer occurs. Clinical application of this concept will
      require optimization of combination therapies analogous to highly active
      antiretroviral therapy (HAART) for HIV infection. Total cure of hepatitis B will
      require elimination of the intranuclear pool of viral minichromosomes, which will
      probably only be achieved by normal cell turnover, reactivation of host immunity,
      or elucidation of the antiviral mechanisms operating during cytokine clearance in
      acute hepatitis B (see Fig. 1).

PMID- 15481343
TI  - Clinical significance of hepatitis B virus genotypes, variants, and mutants.
AB  - Emerging evidence suggests that hepatitis B virus (HBV) genotypes may influence
      the rate of spontaneous and interferon-induced hepatitis B e antigen (HBeAg)
      seroconversion as well as the natural history of liver disease. In contrast, the
      dinical significance of precore and core promoter variants associated with HBeAg
      negative liver disease is less certain in light of the many competing host and
      virologic factors noted in reported studies. HBV surface mutants are primarily
      associated with prior vaccine or hepatitis B immune globulin exposure and do not
      appear to have untoward virulence or association with occult HBV infection.
      Polymerase mutants with reduced drug sensitivity and phenotypic resistance are
      commonly detected in patients receiving prolonged antiviral therapy and have a
      variable impact on disease outcomes. The introduction of additional
      nucleoside/nucleotide analog agents will likely lead to the development of
      further unique polymerase mutants with varying pathogenicity and cross-resistance
      to existing drugs.

PMID- 15481344
TI  - Treatment of hepatitis B with interferon and combination therapy.
AB  - Pegylated interferon alpha-a (40 kDa) has recently been shown to be superior to
      conventional interferon. Furthermore, in a pilot study, pegylated interferon
      alpha-2b together with lamivudine was superior to lamivudine monotherapy.
      Therefore, the pegylated interferons alone or in combination with antiviral
      agents are likely to be the treatment of the future. Selecting patients for
      treatment and knowing when to treat them is as important as knowing which
      medicine to treat them with.

PMID- 15481345
TI  - Antiviral therapy: nucleotide and nucleoside analogs.
AB  - For the management of HBV infection, an increasing number of nucleotide and
      nucleoside analogs are active against wild-type HBV and some against HBV with
      YMDD and other compensatory mutations. Table 2 depicts the IC50 and
      susceptibilities of HBV to various antiviral agents. The dichotomy between in
      vitro and in vivo susceptibilities to YMDD mutants is due to a change in IC50
      between wild-type and mutant virus. Thus a drug may have less activity in vitro
      but at doses used in vivo show activity against YMDD and other compensatory
      mutations. Some HBV drugs share activity against HIV, which may be useful in the
      co-infected patient. Other nucleoside analogs are in various stages of
      development, including MCC-478 and DAPD. In the future, clinicians will have a
      plethora of reagents to chose from, and combination therapies may be invoked.

PMID- 15481346
TI  - Management of hepatitis B in children.
AB  - Children with hepatitis B infection require management by physicians
      knowledgeable about the natural history of this disorder and experienced in the
      treatment of children. Selection of appropriate pediatric patients for treatment
      will prevent some cases of advanced liver disease later in life. New treatments
      under development for adults may benefit children as well, once they have been
      rigorously investigated in the pediatric population. Prevention of new HBV
      infections is an important part of management in children, and working with
      public health campaigns will hopefully reduce both vertical and horizontal
      transmission.

PMID- 15481347
TI  - Extrahepatic manifestations of chronic hepatitis B.
AB  - Several extrahepatic manifestations are associated with chronic HBV infection,
      many with significant morbidity and mortality. The cause of these extrahepatic
      manifestations is generally believed to be immune mediated. PAN is a rare, but
      serious, systemic complication of chronic HBV affecting the small- and medium
      sized vessels. PAN is seen more frequently in North American and European
      patients and rarely in Asian patients. PAN ultimately involves multiple organ
      systems, some with devastating consequences, though the hepatic manifestations
      are often more mild. The optimal treatment of HBV-associated PAN is thought to
      include a combination of antiviral and immunosuppressive therapies. HBV
      associated GN occurs mainly in children, predominantly males, in HBV endemic
      areas of the world, but is only occasionally reported in the United States. In
      children, GN is usually self-limited with only rare progression to renal failure.
      In adults, the natural disease course of GN may be more relentless, slowly
      progressing to renal failure. Immunosuppressive therapy in HBV-related GN is not
      recommended, but antiviral therapy with alpha-interferon has shown promise. The
      serum-sickness like "arthritis-dermatitis" prodrome is seen in approximately one
      third of patients acquiring HBV. The joint and skin manifestations are varied,
      but the syndrome spontaneously resolves at the onset of clinical hepatitis with
      few significant sequelae. Occasionally, arthritis following the acute prodromal
      infection may persist; however, joint destruction is rare. The association
      between HBV and mixed essential cryoglobulinemia remains controversial; but a
      triad of purpura, arthralgias, and weakness, which can progress to nephritis,
      pulmonary disease, and generalized vasculitis, has characterized the syndrome.
      Finally, skin manifestations of HBV infection typically present as palpable
      purpura. Though papular acrodermatitis of childhood has been reported to be
      caused by chronic HBV, this association remains controversial.

PMID- 15481348
TI  - Pathogenesis and screening for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is an increasingly common clinical problem.
      Investigators have begun to understand aspects of the pathogenesis of the tumor,
      mainly from a morphologic point of view. Preneoplastic lesions and early cancer
      may be difficult to distinguish radiologically. Nonetheless, programs for
      surveillance of liver cancer have been developed. Little uniformity exists in
      methods of surveillance, and even less in methods of investigation and follow-up
      after an abnormal result is obtained. This article attempts to bring some rigor
      to the understanding of hepatocellular carcinoma.

PMID- 15481349
TI  - Hepatitis B virus infection: co-infection with hepatitis C virus, hepatitis D
      virus, and human immunodeficiency virus.
AB  - Hepatitis B virus (HBV) shares routes of transmission, namely exchange of
      infected body fluids, sharing of contaminated needles, and blood transfusion,
      with other hepatotropic viruses, such as hepatitis C virus (HCV) and hepatitis D
      virus (HDV) and with systemic retroviral infections, such as the human
      immunodeficiency virus (HIV). Thus, many HBV infected patients are co-infected
      with other viral pathogens. Co-infection appears to increase the risk of
      progression of liver disease and may have important ramifications on choice of
      antiviral medication and treatment regimen. This article reviews the current
      knowledge of co-infection of HBV with HCV, HDV, and HIV.

PMID- 15481350
TI  - Liver transplant and recurrent disease.
AB  - Current prophylactic measures have greatly reduced recurrence rates of hepatitis
      B after liver transplantation. HBIG remains a critically important compound and
      although there is variability in dosing regimens and target anti-HBs levels, it
      is the backbone of recurrence prevention. Adjuvant therapies with
      nucleoside/nucleotide analogs alone have been limited by drug-resistant strains
      of HBV, but the armamentarium of these molecules continues to grow and hence the
      management of the post-LT HBV patient will evolve further. Currently lamivudine
      with HBIG remains an excellent option provided the patient has not developed
      resistance, especially in the pre-LT period. Adefovir is the drug of choice in
      that setting and perhaps the preferred drug in the pre-LT setting to allow the
      use of lamivudine post-LT. Further testing with tenofovir and newer compounds in
      development will expand these options. The use of multiple nucleoside analogs is
      an intriguing option, based on the HIV experience of reducing drug resistance and
      optimizing viral suppression, and will likely be further studied.

PMID- 15481351
TI  - [Clinical signs and diagnosis of a severe primary infection with BVDV subtype 1b
      in a dairy herd].
AB  - As a result of a BVDV infection in a herd consisting of 95 adult cattle 17 cows
      aborted their calves within a period of 3.5 months, one third got severe
      diarrhoea, 3 cows died and an increased percentage of the cattle got lochiometra
      after calving or abortion. The disease was diagnosed by paired serological
      testing of cattle with diarrhoea or abortion and post mortem examination of
      several aborted calves. From one foetus BVDV virus was isolated and subsequently
      subtyped by sequencing. Of aborting cattle, the testing results were influenced
      by the interval between infection and abortion. These results indicate that a
      primary infection with BVDV subtype 1b can cause severe clinical symptoms in a
      dairy herd.

PMID- 15481352
TI  - [A story with a tail].

PMID- 15481354
TI  - [Aggressive behavior in Golden Retrievers: researching the scope of the problem].

PMID- 15481353
TI  - [The cat with exposed tooth roots: a missed diagnosis?].
AB  - The distal roots of the mandibular molars (309 & 409) are often exposed in cats
      with chronic, recurrent inflammation of the oral mucous membranes. The disorder
      can be easily detected during a thorough investigation under light sedation. Some
      reasons are given why the diagnostic investigation is sometimes performed
      incompletely.

PMID- 15481356
TI  - [Reaction to interview with Richard Rieter].

PMID- 15481355
TI  - [Employment disability, not just a matter of income].

PMID- 15481357
TI  - [Darwin not against euthanasia].

PMID- 15481358
TI  - [Large support for voluntary employer organization and voluntary CAO].

PMID- 15481359
TI  - [Results of the questionnaire about employment disability among practicing
      veterinarians].

PMID- 15481360
TI  - The medical liability situation.

PMID- 15481361
TI  - Guarded equanimity.

PMID- 15481362
TI  - Considerations for the 2004-2005 influenza season.

PMID- 15481363
TI  - Ischemic nephropathy in South Dakota: case reports and review.
AB  - Ischemic nephropathy, a relatively new term coined to describe renal
      insufficiency due to renal artery disease, is neither a new subject for medicine
      throughout the country, nor a new problem here in South Dakota. It is an
      important and overlooked cause of renal insufficiency and is almost certainly
      under-diagnosed. Five case reports and a review of the entity are described to
      illustrate the diversity of this clinical presentation. Intervention in such
      cases was thought to preserve, or even improve renal function, delaying the onset
      of end stage renal disease (ERSD).

PMID- 15481364
TI  - [Organ distribution of cardiac output in resting mammals].

PMID- 15481365
TI  - [Regulation of the adenylate cyclase signaling system in cultured Dileptus anser
      and Tetrahymena pyriformis by insulin peptide superfamily].

PMID- 15481367
TI  - [Application of bisalkaloid derivatives of dicarboxylic acids based on lupinine,
      anabasine and cytisine as cholinesterase inhibitors of various origin].

PMID- 15481366
TI  - [Enzymes of carbohydrate and energetic cycles in the turbellarian Phagocata
      sibirica].

PMID- 15481368
TI  - [Heterogeneity and functional variation of hemoglobins in Diptera, Chironomidae].

PMID- 15481369
TI  - [Substrate activation of Ca(2+)-ATPase in sarcoplasmic reticulum in skeletal
      muscles of ectothermic animals].

PMID- 15481370
TI  - [Properties of Cl(-)-stimulated and sensitive to inhibitory receptor ligands
      Mg(2+)-ATPase in plasma membrane of the Abramis Brama brain].

PMID- 15481371
TI  - [Stimulating effect of insulin and epidermal growth factor on activity of protein
      kinase A, glucose 6-phosphate dehydrogenase and glycogen synthetase in skeletal
      muscles of chickens and chicken embryos].

PMID- 15481372
TI  - [Insulin-regulated adenylate cyclase signaling system of rat skeletal muscles
      after insulin administration and in insulin deficiency caused by streptozotocin
      induced diabetes].

PMID- 15481373
TI  - [Influence of the fraction 1-10 kD from the bear (Ursus arctos) brain on mice and
      rats].

PMID- 15481374
TI  - [Lung response to stress based on metabolic parameters at various stages of
      postnatal ontogenesis].

PMID- 15481375
TI  - ["Sleeping" mechanisms in the regulation of K/Na homeostasis in rat
      cardiomyocytes in hypoxia].

PMID- 15481376
TI  - [Transformation of sensory neurons into associative neurons in the epidermal
      plexus and ganglia of Bilateria].

PMID- 15481377
TI  - [Structural and cytochemical parameters of basement membranes in regions of blood
      brain barrier development during human prenatal ontogenesis].

PMID- 15481378
TI  - [Natalia Petrovna Bekhtereva (on 80th birthday)].

PMID- 15481379
TI  - [Platon Grigor'evich Kostiuk (on 80th birthday].

PMID- 15481381
TI  - [Changes in the cortical electric activity in the course of set formation under
      conditions of increased loading of the working memory].
AB  - Stability of the cognitive set to nonsense words in healthy adult subjects was
      compared in two experimental conditions: (1) subjects had only to recognize
      pseudowords/words; (2) in each trial after the pseudoword/word recognition,
      subjects had to press a button in response to a visual probe stimulus and only
      after this action to pronounce a recognized pseudoword/word. It was shown that
      complication of the cognitive performance in the second condition did not affect
      the set rigidity. However, the pattern of the cortical electric activity
      substantially changed: the EEG power in the theta frequency range and coherence
      function, in particular, interhemispheric, in the frontal cortical areas were
      higher in the second condition. The increase in coherence function in the frontal
      areas was most pronounced in the theta and alphal ranges. It was suggested that
      increase in activity of the frontal regions of the brain cortex facilitates
      shifts of visual sets under increasing load of the working memory.

PMID- 15481380
TI  - "Apoptotic" mechanisms in normal brain plasticity: caspase-3 and long-term
      potentiation.
AB  - The analysis of recent data indicates that a few enzymes that have been
      recognized as "apoptotic" so far may be involved in important cellular processes
      not related to cell death in the brain. For example, it can be demonstrated that
      caspase-3, an "apoptotic" enzyme that is active in neurons is necessary for
      normal neuroplasticity. Here we discuss the involvement of caspase-3 in long-term
      potentiation phenomenon. Proteins that are key players of molecular mechanisms of
      long-term potentiation induction and maintenance are also caspase-3 substrates. 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.

PMID- 15481382
TI  - [Gender differences in resting EEG related to Eysenk's Personality Traits].
AB  - EEG mapping was used to study gender differences in hemispheric organization
      related to personality (40 male and 42 female subjects, the students 17-20 ages).
      The results showed, that each clearly defined personality trait (neuroticism,
      extraversion, psychoticizm and social conformity) characterized by special EEG
      pattern differenced on men and women groups. At the same time, more close
      interaction of gender and neuroticism was observed, but gender and extraversion
      were less connected. Neuroticism related patterns of coherence in the alpha2- and
      beta2-bands were associated with an activity changes in anterior cortex in men
      but posterior--in women, at that the positive correlations were observed in the
      beta2-band in the former case and negative ones in the second. There are two
      opposing tendencies of the interaction between extraversion and gender in a
      modulation of the resting theta-rhythm: an increase of cortex connections in men
      and decrease ones in women. The specificity of spatial-temporal EEG patterns in
      men associated mostly with a psychoticizm value but in women--with a social
      conformism. In either case these personality traits related to activity of
      frontal cortex in the left hemisphere.

PMID- 15481383
TI  - [Spectrum and coherent characteristics of bioelectric activity of the brain in
      women with normal and complicated pregnancy].
AB  - Spectrum and coherent EEG analysis was performed in 86 pregnant women on the 35
      36th week of gestation. It was shown that functional interhemispheric brain
      asymmetry is a sensitive index of normal and complicated gestation. It was found
      out that activation prevailing in the central and temporal brain areas
      contralateral to the side of placenta localization in the uterus was
      characteristic of the normal pregnancy. The development of gestation
      complications was accompanied by the inversion of interhemispheric asymmetry of
      EEG activation. It was suggested that correlative properties of bioelectric brain
      activity in women with normal gestation are an indicator of the left-hemispheric
      dominance of brain centers in the integration process.

PMID- 15481384
TI  - [Event-related synchronization and desynchronization of EEG during appraisal of
      threatening and pleasant visual stimuli in high anxious subjects].
AB  - The 62-channel EEG was recorded while low (LA, n = 18) and high (HA, n = 18)
      trait-anxious subjects viewed sequentially presented neutral, threatening and
      pleasant IAPS stimuli. Event-related desynchronization (ERD) and synchronization
      (ERS) were studied in the delta, theta1, theta2, alpha1, alpha2, beta1, beta2,
      beta3, and gamma frequency bands. Between-group differences, related to stimulus
      emotionality, were linked to theta1 and theta2 bands. In the low theta at
      prefrontal sites in the test period of 100-700 ms after stimulus onset HA
      exhibited relative predominance of the left hemisphere in response to both
      threatening and pleasant stimuli, whereas LA yielded larger right than left
      hemisphere activity in response to all the three stimulus categories. In the
      upper theta band between group differences were associated with posterior
      cortical regions and the test period of 0-1000 ms after stimulus onset: HA
      exhibited the largest ERS to threatening, whereas LA prompted the largest ERS to
      pleasant stimuli. Finally, according to the ERD data, in the alpha1 band HA
      participants in comparison with LA revealed enhanced left hemisphere activation
      in response to all the stimulus categories. It is suggested that as it is indexed
      by theta-ERS relative predominance of the left hemisphere at prefrontal sites
      along with the largest bilateral activity of posterior cortical regions (i.e.,
      enhanced higher order visual processing) to threatening stimuli could form the
      basis for general bias towards threatening information in HA at the very early
      stages of emotional processing.

PMID- 15481385
TI  - [Construction in chimpanzees].
AB  - Chimpanzees with the help of reconstruction and the "step-by-step" analysis of a
      figure--sample can plan a circuit of actions, forming an image of an end result.
      Ability to such actions proves at them an opportunity of cogitative operations,
      allowing to collect multielement figures on a sample. Generalization of concrete
      operations with concrete elements creates the precondition for the generalized
      understanding of a principle of actions--knowledge--in general to collect
      separate elements in complex designs. In it the powerful conceptual potential
      chimpanzees is covered. It allows to use chimpanzees as model preverbal a level
      of thinking.

PMID- 15481386
TI  - [The influence of systemically administered selective dopamine antagonists of D1
      and D2/D3 types on alimentary and escape conditioned placing reactions in cats].
AB  - Systemic administration of the specific antagonists of D1 (SCH23390, 0.005-0.1
      mg/kg) and D2/D3 (raclopride, 0.1-0.25 mg/kg) dopamine receptors leeds to dose
      dependent increase of the reaction time and decrease of conditined reflex
      probability up to full blocking (in the case of SCH23390) of alimentary and
      escape conditioned placing reaction in cats. The action of both antagonists was
      far more suppressive regarding conditioned escape reflex. The action of SCH23390
      was far more effective than that of raclopride concerning both types of
      conditioned reflexes.

PMID- 15481387
TI  - [Dopaminergic modulation of impulse activity of sensorymotor cortex neurons
      during conditioned reflex].
AB  - Changes of conditioned impulse reaction of cortical neurons wer studied during
      microiontophoretic application of agonist and antagonists of glutamate and GABA
      transmission and their modulation by dopamine. It was shown paradoxal reaction of
      facilitation of impulse activity during iontophoretic application of ionotropic
      glutamate antagonist and depressive influences of metabotropic antagonist. Local
      iontophoretic application of dopamine increased background and evoked impulse
      activity of pyramidal neurons of deep layers of cortex and eliminated inhibitory
      influences of glutamate metabotropic antagonist MCPG. It is concluded that DA has
      stabilizing effects on activity of cortical neurons. It is suppose that these
      effects of DA realize through system of inhibitory interneurons.

PMID- 15481388
TI  - [The individual organization of frontal-hippocampal networks during realization
      of different behavioral tasks].
AB  - Four cats were subjected to appetitive instrumental conditioning with light as a
      conditioned stimulus by the method of "active choice" of the reinforcement
      quality: short-delay conditioned bar-press responses were followed by bread-meat
      mixture and the delayed responses--by meat. The animals differed in behavior
      strategy: four animals preferred bar-pressing with long delay (so called "self
      control" group); two animal preferred bar-pressing with short-delay (so called
      "impulsive" group). Then all the animals were learned to short-delay (1 s)
      instrumental conditioned reflex to light (CS+) reinforced by meat. The multiunit
      activity in the frontal cortex and the hippocampus (CA3) was recorded through
      chronically implanted nichrome-wire semimicroelectrodes. The interactions among
      the neighboring neurons in the frontal cortex and hippocampus (within the local
      neuronal networks) and between the neurons of the frontal cortex and hippocampus
      (distributed neuronal networks of frontal-hippocampal and hippocampal-frontal
      directions) were evaluated by means of statistical crosscorrelation analysis of
      the spike trains. Crosscorrelation interneuronal connections in the delay range 0
      100 ms were explored. It was shown that the functional organization of the
      frontal and hippocampal neuronal networks differed in choice behavior and was
      similar during realization of short-delayed conditioned reflex. We suggest that
      the local and distributed neural networks of the frontal cortex and hippocampus
      take part in the realization of cognitive behavior, in particularly in the
      processes of the decision making.

PMID- 15481389
TI  - [Brain monoamine oxidase in highly aggressive C57BL and low aggressive CBA mice].
AB  - Highly aggressive C57BL mice were characterized by a higher MAO A activity in
      brain stem and hemispheres than low aggressive CBA mice at the age of 2 and 6
      months. Emotional stress provoked by restraint resulted in a decrease of MAO A in
      the brain stem and hemispheres in 2-month-old C57BL mice which was prevented by
      actinomycin D. MAO A and MAO B in CBA mice did not react to stress. Aging of
      C57BL mice was accompanied by a decrease of MAO A activity in the hemispheres and
      of MAO B in the brain stem, while in CBA mice it was accompanied by a decrease of
      MAO B activity in the hemispheres. Actinomycin D increased MAO A activity in the
      brain stem of 6-month-old C57BL mice, but did not influence brain MAO in CBA
      mice. These date have demonstrated that the genotype of highly aggressive C57BL
      mice, as compared to low aggressive CBA mice, was expressed in a higher brain MAO
      A activity, which may have contributed to manifestation of aggressiveness in
      adult animals and of more reactive MAO A, which may be associated with
      peculiarities of regulation of its activity at the level of transcription but
      does not lead to disappearance of aggressiveness.

PMID- 15481391
TI  - [Changes in brain serotonin metabolism and [3H]-serotonin receptor binding during
      recall of conditioned passive avoidance in rats].
AB  - The content of serotonin and its metabolite 5-hydroxyindoleacetic acid, monoamine
      oxidase activity, and [3H]-serotonin radioligand receptor binding were examined
      in the prefrontal cortex, striatum, amygdala, hippocampus and periaqueductal gray
      matter at different time after one-trial passive avoidance training of rats.
      Changes in the serotonergic activity were observed only in rats, which showed
      retrieval of conditioned passive avoidance response. No serotonergic changes were
      found immediately and one day after training. Also, there were no changes in
      trained rats without retrieval of conditioned passive avoidance response or rats
      with experimental amnesia. The pattern of the involvement of brain structures in
      the retrieval process was also revealed. [3H]-serotonin binding was decreased in
      the amygdala, periaqueductal gray matter and striatum, whereas it did not change
      in the prefrontal cortex and hippocampus. At the same time, the serotonin content
      in these structures did not differ from that of intact rats. Deamination of
      serotonin by monoamine oxidase and active transport of 5-hydroxyindoleacetic acid
      from nerve terminals were increased in the amygdala and periaqueductal gray
      matter, whereas in the striatum serotonin catabolism was decreased. The obtained
      differences in serotonin catabo- lism suggest that the decrease in receptor
      binding of serotonin in these brain structures is provided by different synaptic
      processes: presynaptic changes in the striatum and postsynaptic receptor changes
      in the amygdala and periaqueductal gray matter. It is concluded that the decrease
      in the serotonergic activity in the amygdala and periaqueductal gray matter
      represents one of the mechanisms activating the emotiogenic system mediating the
      memory trace retrieval in inhibitory avoidance learning.

PMID- 15481390
TI  - [Vesicular and nonvesicular glutamate release in the nucleus accumbens during a
      forced switch in behavioral strategy].
AB  - By means of in vivo microdialysis combined with HPLC analysis, we have shown that
      glutamate extracellular level in the rat n. accumbens increases during a forced
      switch in behavioral strategy. When infused in the n. accumbens, a Na+ channel
      blocker tetrodotoxin (TTX, 1 microM) completely prevents this increase whereas a
      potent cystine/glutamate exchanger blocker (S)-4-carboxyphenylglycine ((S)-4-CPG,
      5 microM) has no effect. In contrast, TT (1 microM), infused in the n. accumbens,
      fails to significantly alter basal level of extracellular glutamate in this
      region whereas (S)-4-CPG (5 microM) produced a significant decrease. Our data
      suggest that basal and factional glutamate releases in the n. accumbens are
      differently regulated. The source of basal glutamate release is a non-vesicular
      release via cystine/glutamate exchanger. Functional glutamate release observed
      during a forced switch in behavioral strategy derives from vesicular synaptic
      pool.

PMID- 15481392
TI  - [Study of synaptic plasticity of hippocampal CA3 area as a result of tetanization
      of perforant path].
AB  - Evoked responses in CA3 area to the mossy fibers stimulation were studied after
      low and high frequency tetanizations of the perforant path. Stimulations of
      perforant path with 10 and 100 Hz frequencies inducted depression testing through
      the same path. Subthreshold for potentiation of the mossy fibers inputs to the
      CA3 tetanization of the perforant path with 10 Hz frequency transformed to
      threshold one after previous tetanization of the perforant path with 100 Hz
      frequency. Tetanization of the mossy inputs to the CA3 with 10 Hz frequency
      leaded to potentiation whereas tetanization with frequency 100 Hz depressed the
      same inputs. High frequency tetanizations (100 Hz) of the perforant path with
      theta-rithm frequency stimulation basically depressed of the CA3 evoked responces
      to the mossy fiber stimulation.

PMID- 15481393
TI  - [Patterns of maternal behavior of rats genetically selected for opposite coping
      styles].
AB  - Maternal behavior of Koltushi High- and Low-avoidance (KHA and KLA) rats strains
      was assessed over the prewealing period (days 6-21). Ten litters of each strain
      were observed during the light phase of the light/dark cycle. In a series of
      experiments, rat pups were taken from the maternal nest and placed into the
      opposite corner of the cage. The following parameters of the maternal behavior
      were recorded: the latency of the first contact with the pups, pup licking,
      latency of carrying/retrieval of the first pup back to the nest, time of
      returning to the nest of the whole litter, and mother's spontaneous behavior
      (grooming and locomotion time) over the course of 10 min of observation. KLA
      mothers stayed with their pups and took care of them more frequently than KHA
      mothers during the light phase of the circadian cycle. Time of self-grooming was
      significantly higher in KHA rats. The highest levels of self-grooming of mothers
      was registered on the first day of testing. The latency of the first coming to
      pups after their removal from the nest was lower in KHA rats, but they needed
      more time to returned all pups to the nest. The experimental evidence suggests
      that the KHA but not KLA rats with the active coping style and higher stress
      reactivity display disorders in maternal behavior in a novel situation.

PMID- 15481394
TI  - [Inositoltriphosphate receptors and ryanodine receptors in regulation of
      cholinosensitivity of Helix lucorum neurones by Na,K-pump during habituation].
AB  - Influence of ouabain, the inhibitor of Na,K-pump, on habituation of Helix to
      tactile stimulation was identical to the ouabain-induced modification of
      cholinosensitivity reduction in command neurones of defensive behaviour of Helix
      lucorum in cellular model of habituation. Effects of intracellularly injected
      ligands of two types of Ca2+ -depot receptors, inositoltrisphosphate (IP3) and
      ryanodine receptors, on ouabain-induced changes were studied in cellular model of
      habituation. The antagonist of IP3 receptors heparin (0.1 mM), their agonist IP3
      (0.1 mM) and inhibitor of ryanodine-dependent Ca2+ mobilization dantrolen (0.1
      mM) prevented the depression of acetylcholine-induced current from the ouabain
      evoked modification. The agonist/antagonist of ryanodine receptors ryanodine at
      two tested concentrations (0.1 mM and 1 mM) did not change the ouabain effect. It
      is concluded that Ca2+ released from intracellular Ca2+ -depots via IP3 receptors
      is involved into neuronal mechanism of Na,K-pump regulation of habituation in
      Helix lucorum to tactile stimulation.

PMID- 15481395
TI  - [Ephaptic feedback in identified synapses of terrestrial snails].
AB  - A hypothesis for the existence of the intrasynaptic ephaptic feedback (EFB) in
      the invertebrate central nervous sytem was tested. Excitatory postsynaptic
      potentials (EPSPs) and currents (EPSCs) evoked by the activation of the recently
      described monosynaptic connection between the identified snail neurons were
      recorded intracellularly. In case of the EFB presence, the postsynaptic
      tetanization with hyperpolarization pulses could activate presynaptic Ca2+
      channels and enhance the EPSP amplitude, whereas a steady postsynaptic
      hyperpolarization should induce a "supralinear" increase in EPSC amplitudes as it
      has been found in the rat hippocampus. In the first series of the experiments, 10
      trains of hyperpolarizing pulses (40-50 mV, 1 Hz, pulse duration 0.5 s, train
      duration 45 s) were delivered postsynaptically. No significant changes in EPSP
      amplitudes were found. In the second series of the experiments, the EPSC
      amplitudes were measured during varying postsynaptic hyperpolarization. At the
      membrane potential 100 mV, the EPSP amplitude was significantly higher than
      theoretically predicted from the classical linear dependence. Such a
      "supralinear" effect of postsynaptic depolarization can be explained by the
      presence of the EFB. This finding is the first evidence for the EFB existence in
      the invertebrate central nervous system.

PMID- 15481396
TI  - Health professions education and you.

PMID- 15481397
TI  - A cornerstone for practice.

PMID- 15481398
TI  - Bariatric surgery.

PMID- 15481399
TI  - Using WebQuests to promote active learning.

PMID- 15481400
TI  - Educating nurses for leadership roles.
AB  - As a result of the growing shortage of nurses and the dramatically changing role
      of the front-line nurse manager, leadership education for nurses is of critical
      importance. The purpose of the project described in this article was to design,
      implement, and evaluate an innovative model of nursing leadership development for
      students enrolled in registered nurse to bachelor of science in nursing or
      registered nurse to master of science in nursing programs. A guided "action
      learning" course was designed that focused on both core knowledge and
      experiential learning. The course was developed with the assistance of an
      advisory panel of prominent nurse leaders with expertise in administration,
      health policy, informatics, and nursing education. The prototype course was
      offered for the first time as an elective in Spring 2003. Evaluation data
      indicated that the course was considered valuable by students and with
      modifications suggested by students, faculty, and advisory panel members, the
      course would be offered regularly as part of the curriculum. Recommendations also
      included adapting course content to a continuing education format.

PMID- 15481401
TI  - Reduce the nursing shortage: help inactive nurses return to work.
AB  - One solution to alleviate the nursing shortage is to help inactive nurses return
      to work. A self-directed refresher course at Tennessee State University School of
      Nursing is meeting the challenge to help inactive registered nurses return to
      practice. The course allows inactive nurses autonomy in scheduling their
      individual study and their clinical experiences. A survey, sent to nurses who
      completed the course, revealed that the flexible schedule was the key factor in
      their ability to return to practice. Refresher courses are one option to increase
      the number of registered nurses.

PMID- 15481402
TI  - Advanced Organizers: a framework to implement learning readiness in support of
      broad-scale change.
AB  - Staff development educators are challenged to bring value to the adoption of new
      organizational management tools to improve the health care of patients. One
      strategy used to pursue health care excellence is the adoption of the ISO 9000
      standards. However, implementation of this quality management system requires
      acceptance at all levels of the healthcare organization. This article explores
      the concept of learning readiness and uses an example of a training design
      strategy called an "Advanced Organizer." The authors describe its use as a
      development readiness strategy, outline the methodology for development and
      implementation, and provide steps for successful implementation. The implications
      for staff development educators are reviewed for the concept of learning
      readiness and broad-scale performance improvement initiatives.

PMID- 15481403
TI  - Development of a web-based genetics institute for a nursing audience.
AB  - The purpose of this article is to serve as a resource for readers considering the
      development of a web-based continuing education offering in their particular
      specialty areas. A theory-based instructional design using a face-to-face
      genetics summer institute as a content template and incorporating several levels
      of planned formative evaluation are described. Summative evaluation strategies
      revealing satisfaction with the format, improved knowledge, and ability to use
      genetics knowledge in participants' work setting are also discussed. Finally,
      lessons learned following completion of two 18-week web-based genetics institutes
      are shared.

PMID- 15481404
TI  - Preceptors' expectations: an avenue to foster appropriate clinical experiences
      for advanced practice nursing students.

PMID- 15481405
TI  - [Investigation of sleep disorders in the vicinity of high frequency
      transmitters].
AB  - To investigate the potential impact of RF electromagnetic fields of transmitters
      on the sleep quality of nearby residents, a new study design is presented. In a
      double-blind crossover field study the effect of on-site shielding, rather than
      of additional exposure, is investigated. For improved sleep quality
      differentiation the polysomnographic parameters are expanded by additional
      parameters. The feasibility study showed that checking the raw data and
      correcting the software-generated results by visual reading of the
      polysomnographic recordings is essential. Long-term RF measurement showed that
      exposure may vary considerably throughout the night, as well as from one night to
      the next. This variation may be greater than the GSM contribution itself. Mostly,
      the contributions of USW radio frequency fields dominated over GSM. Thus,
      continuous broadband RF recording is required for reliable interpretation of the
      results, in particular with regard to the potential role of mobile telephony
      emissions. Results show that simple sleep monitoring systems based on single
      channel EEG analysis without acces to original biosignals are not adequate for
      sleep studies.

PMID- 15481406
TI  - [A method for improving measuring accuracy in multi-channel impedance
      spectroscopy (MIS)].
AB  - The use of impedance spectroscopy as a diagnostic tool for the investigation of
      biological objects involves the consideration of numerous parameters impacting on
      measuring accuracy. This paper describes a calibration method for multichannel
      instruments that reduces the non-inconsiderable influence of frequency response
      variations between the channels, thus significantly increasing measuring
      accuracy. The method is tested in a recently developed, high-resolution, multi
      channel bio-impedance analyser. Reduction of the measuring error is demonstrated,
      and the magnitude and phase resolution is quantified. The advantage of this
      method lies in its applicability to existing systems. Furthermore, an additional
      calibration impedance is not needed.

PMID- 15481407
TI  - [Image-guided navigation for the control interstitial laser therapy of vascular
      malformations in the head and neck region].
AB  - Laser-induced interstitial thermal therapy (LITT) is a proven minimally invasive
      surgical technique for the treatment of haemangiomas and vascular malformations,
      and various tumours. The intra-lesion application of thermal energy destroys
      regional tissue. The percutaneous placement of the laser fibre for
      photocoagulation is done without the benefit of direct visual control. Image-data
      based LITT was performed in patients (five procedures) with extensive venous
      malformations in the maxillofacial area. The system comprised a specially
      developed Nd:YAG laser fibre introducer set used in conjunction with fused high
      resolution computed tomography, and magnetic resonance image-data--based surgical
      navigation. In all cases, follow-up examination clearly showed a diminishment in
      tumour volume, and all patients reported significant subjective improvement. The
      results suggest that navigation-guided LITT can be performed safely, preserving
      vital structures from collateral thermal damage.

PMID- 15481408
TI  - [Central cable system--fully automatic, continuous distraction osteogenesis for
      the lengthening treatment of large bone defects].
AB  - Distraction osteogenesis involving bone transport enables the reconstruction of
      large bone defects. The main bone fragments are usually stablilised externally,
      an intermediate bone segment is separated and moved through the defect at a rate
      of about 1 mm/day. New high-quality bone is built up in the constantly enlarging
      osteotomy gap. A major problem associated with the method is the fact that the
      fixation pins are also moved over the same distance, and cut through the soft
      tissue, often resulting in painful pin tract infections and ugly scars. An
      automatic motorized bone transport system employing a single central cable now
      eliminates this problem. The system can be combined with any external fixateur,
      since the relevant implanted parts for bone transport are independent of the
      external stabilizer. The surgical procedure, which is easy on the patient,
      consists of bone segment separation, central cable fixation, and stabilisation of
      the main fragments, and requires the use of numerous special tools. The
      distraction itself results in significantly less soft tissue irritation and pain.
      Pin tract infections are rare, so that changeover to internal fixation after
      completion of bone transport carries little risk of infection. This article
      details the technical features of the stabilizing system and the transport and
      the control systems, and describes the clinical application in a patient.

PMID- 15481409
TI  - [Design and testing of a novel measuring system for use in dental biomechanics-
      principles and examples of measurements with the hexapod measuring system].
AB  - A novel measuring set-up based on a hexapod system for use in dental biomechanics
      is described. It was specially developed to measure force/deflection
      characteristics of different dental materials and devices. The functionability
      and suitability of the system for use in experimental biomechanics were
      investigated in two different studies. In a first study the micro mobility of
      prosthetic telescopic crowns prior to and after simulated wear was determined to
      investigate the influence of wear processes on the stability of the anchorage
      elements and thus of prostheses. This study investigated the ability of the setup
      to load a specimen with high forces or torques of up to 100 Newton. The second
      study looked at the force/deflection characteristics of orthodontic anchorage
      pins used in orthodontics to additionally stabilize the anchorage unit, for
      example during molar movement. In this study specimens were loaded with small
      forces of less than 10 Newton, as are typically used in orthodontics. Using the
      setup, the deflection behaviour of these devices under high and low loading was
      measured at a resolution of approximately one micrometer or one angular second.

PMID- 15481410
TI  - [The modular hip revision stem made of titanium alloy--influence and optimisation
      of bending stiffness].
AB  - The MRP-Titan Revision stem has proved to be a highly successful implant system
      for revision arthroplasty of the hip. Good and excellent clinical and
      radiological results with spontaneous filling of bony defects have been reported,
      The observation of atrophy of the proximal femur associated with stem diameters >
      17mm prompted us to examine the bending stiffness of stems of various diameters.
      To determine their static bending characteristics, the stems were tested under
      axial pressure loads in accordance with Euler's buckling case. Dynamic tests were
      performed with the mono-axial servohydraulic test equipment MTS 810. From a stem
      diameter of 18 mm upwards, deflection of the stem under loading decreased
      disproportionately, in direct correlation with the stem stiffness. By optimising
      the geometry and varying the alloy it is possible to obtain a constant ISD factor
      for the modular MRP-Titan revision stem CONCLUSION: The MRP-Titan revision stem
      is a reliable implant system for revision arthroplasty of the hip. Clinical
      findings of atrophy of the proximal femur associated with stem diameters > 17 mm
      was found to be correlated with a disproportionate increase in bending stiffness.
      The aim of further developments will be to reduce the stiffness of larger
      diameter stems by making changes to the design and/or to the alloy (Ti15Mo,
      Ti13Nb13Zr, Ti12Mo6Zr2Fe2).

PMID- 15481411
TI  - Orthopaedic concerns in children with growth hormone therapy.
AB  - Growth hormone (GH) therapy is widely used in children; it may have various
      severe orthopaedic complications. Slipped capital femoral epiphysis, Legg-Calve
      Perthes disease, scoliosis and carpal tunnel syndrome may occur with GH
      treatment. Before beginning GH therapy, it is important to take into account all
      the risk factors of the individual patient, as some conditions could
      contraindicate GH treatment. During GH treatment, close monitoring with both
      clinical and radiographic examination is mandatory. The paediatric orthopaedic
      surgeon will frequently be asked about the management of these complications and
      about the necessity for treatment arrest. The authors review the orthopaedic
      complications which the orthopaedic surgeon may encounter in patients treated
      with GH.

PMID- 15481412
TI  - Debridement arthroplasty for osteoarthritis of the elbow (Outerbridge-Kashiwagi
      procedure).
AB  - The Outerbridge-Kashiwagi (O-K) procedure has been described to treat mild to
      moderate osteoarthritis of the elbow. We treated a consecutive series of 15
      patients (16 elbows) with the O-K procedure. All patients were reviewed after a
      mean follow-up of twenty months (range 3-64 months). The purpose of this study
      was to evaluate the results of the O-K procedure. Assessment included evaluation
      of elbow pain, range of motion and the Mayo elbow Performance Index (MPI). The
      mean arc of motion improved from 94 degrees (range, 65 degrees-120 degrees)
      preoperatively to 114 degrees (range 93 degrees-128 degrees) at the time of
      follow-up (p < 0.01). At the latest follow-up evaluation the total MPI improved
      from 63 (range, 50-75) to 88 (range, 45-100) (p < 0.01), eight elbows (50%) had
      no pain, seven (43.8%) mild pain and one (6.2%) moderate pain. The result was
      excellent for 8 elbows (50%), good for 6 (37.5%), fair for one (6.2%) and poor
      for one (6.2%). Patients' satisfaction showed that thirteen (86.6%) were much
      better or better and two (13.3%) were not improved compared with the preoperative
      situation.

PMID- 15481413
TI  - Minifragment plating for fractures of the distal radius.
AB  - Twelve patients with fracture of the distal radius were treated by open reduction
      and internal fixation with titanium minifragment plates. There were 8 women and 3
      men, with a mean age of 42 years. The mean follow-up was 18 months. According to
      the score of Gartland and Werley, 11 patients had an excellent result and one
      patient had a good result. All patients reported no pain in their activities of
      daily living and were satisfied with the result. All workers returned to work.
      One patient developed reflex sympathetic dystrophy which resolved with treatment.
      No patients needed plate removal because of irritation of the tendons. The
      results obtained with this technique appear promising, although more cases are
      needed to achieve a definitive conclusion.

PMID- 15481414
TI  - Is the Charnley evolution working? A five-year outcome study.
AB  - Two hundred consecutive primary total hip arthroplasties (196 patients) carried
      out between January 1994 and May 1995 using the Elite Plus cemented femoral
      components (DePuy International, Leeds, UK) were enrolled in a prospective study.
      Fifteen patients were lost to follow-up. The patients were evaluated clinically
      using the Harris Hip Score (HHS) and radiographically. The mean HHS was raised
      from 39.3 preoperatively to 89.6 at 5 years. Radiologically the mean femoral
      subsidence was 1.40 mm at 5 years. The mean annual rate of re-operation was 0.2%.
      There were no revisions for aseptic loosening. In the present series, the Elite
      Plus hip arthroplasty has produced clinical and radiological results, which are
      comparable with the Charnley hip at five years.

PMID- 15481415
TI  - The long term fate of the fibula when used as an intraosseous graft.
AB  - The long term fate of the fibula in an intra-osseous site is still a matter of
      debate. Since the procedure of free fibular grafting for neglected femoral neck
      fractures was routinely done at our institute, we were able to observe the serial
      changes in 37 cases with an average 8.9 years follow-up. Graft incorporation was
      not consistent in the 4 to 10-year postoperative period, but in cases with more
      than 10 years follow-up, a major portion of the graft got incorporated into the
      host bone. A classification system for the incorporated grafts is suggested. The
      presence of avascular necrosis seems to initially hinder graft incorporation, but
      if the bone revascularises, graft incorporation proceeds at a comparable rate.
      This study shows that cortical bone gets well incorporated into host cancellous
      bone and helps to reconstitute the neck in cases of femoral neck nonunions.

PMID- 15481416
TI  - Early prophylactic autogenous bone grafting in type III open tibial fractures.
AB  - The authors report the results achieved in patients with type III open tibial
      fractures who underwent primary autogenous bone grafting at the time of
      debridement and skeletal stabilisation. Twenty patients with a mean age of 35.8
      years (range, 24-55) were treated between 1996 and 1999. Eight fractures were
      type IIIA, 11 were type IIIB, and 1 was type IIIC. At the index procedure, wound
      debridement, external fixation and autogenous bone grafting with bone coverage
      were achieved. The mean follow-up period was 46 months (range, 34-55). The mean
      time to fixator removal was 21 weeks (range, 14-35), and the mean time to union
      was 28 weeks (range, 19-45). Skin coverage was achieved by a myocutaneous flap in
      2 patients, late primary closure in 4, and split skin grafting in 14. One (5%) of
      the patients experienced delayed union, and 1 (5%) developed infection. In tibial
      type III open fractures, skin coverage may be delayed, using the surrounding soft
      tissue to cover any exposed bone after thorough debridement and wound cleansing.
      Primary prophylactic bone grafting performed at the same time reduces the rate of
      delayed union, shortens the time to union, and does not increase the infection
      rate.

PMID- 15481417
TI  - Anterior lumbar interbody fusion using a hybrid graft.
AB  - This prospective study evaluates the clinical and radiological results of
      anterior lumbar interbody fusion using a femoral cortical ring allograft (FCA)
      packed with cancellous autologous bone (hybrid graft), combined with posterior
      pedicular fixation but without posterior fusion, for symptomatic degenerative
      disease of the lumbar spine. Twenty-eight out of 30 consecutive adult patients
      were followed up for a minimum period of 2 years. Intra- and postoperative
      complications were seen in 2 out of 28 patients (7%); no complications resulted
      from the allografts. Clinically, 24 out of 28 patients (85%) had a good to
      excellent result, one patient (4%) a fair result, and 3 patients (11%) a poor
      result. Radiologically, the overall fusion rate by the level was 98% in 28
      patients.

PMID- 15481418
TI  - Operative treatment for degenerative lumbar spinal canal stenosis.
AB  - The authors have made a retrospective study of a cohort of patients who underwent
      surgery for spinal stenosis. A total of 85 patients were surgically treated for
      spinal stenosis between 1993 and 1997, and 79 patients were available for re
      evaluation. The average time of follow-up was 79 months. Twenty patients with
      monosegmental stenosis underwent fenestration and undercutting, 16 patients had a
      hemilaminectomy or laminectomy and 43 patients had an instrumented fusion after
      decompression. The severity of the clinical complaints, the degree of stenosis
      and the extent of the instability determined the method of operation used.
      Results were more variable when extensive decompression (hemilaminectomy or more)
      was needed and segmental stability was reduced by resection of large portions of
      the facet joints. Instability clearly worsened the results. The overall results
      clearly show that limited decompression is an ideal operative method, provided
      the indication is correct. Fusion cannot be avoided if segmental instability is
      present. This retrospective study shows that satisfactory long-term results can
      be achieved in lumbar spinal stenosis with surgery adapted to the degree of
      instability and the degree of stenosis.

PMID- 15481419
TI  - Results of surgical treatment for kyphotic deformity of the spine secondary to
      trauma or Scheuermann's disease.
AB  - The authors have performed a retrospective study of 20 patients who underwent
      surgical treatment for kyphosis secondary to trauma (10 patients) or
      Scheuermann's disease (10 patients) between 1992 and 2000. The mean follow-up was
      60 months (range, 32-90) and 59.5 months (range, 24-109) respectively.
      Radiological evaluation of Scheuermann kyphosis included assessment of thoracic
      kyphosis angle (TKA), lumbar lordosis angle (LLA), scoliosis angle (SA) and
      sagittal vertical axis (SVA); radiological evaluation of post-traumatic kyphosis
      included the determination of local kyphosis angle (LKA) and SA, if present. A
      posterior approach was performed in 6 cases and a combined anterior and posterior
      approach was performed in 4 cases of SD whereas patients with post-trauma
      kyphosis were treated using an anterior approach in one case, a posterior
      approach in another and a combined anterior and posterior approach in 8 cases.
      The mean TKA in Scheuermann cases was 71 degrees (65 degrees-80 degrees)
      preoperatively and 41 degrees (31 degrees-52 degrees) postoperatively. There was
      a mean loss of correction of 5 degrees. No positive sagittal balance was present
      during follow-up. The mean TKA in post-trauma cases was 38 degrees (25 degrees-62
      degrees) pre-operatively and 14 degrees (range -15 degrees-28 degrees)
      postoperatively. At the last visit, the mean loss of correction was 2 degrees.
      Proximal junctional kyphosis developed in two cases with Scheuermann kyphosis (17
      degrees and 13 degrees) and in one case with post-traumatic kyphosis (17
      degrees). These findings show that good results can be achieved in the treatment
      of kyphosis secondary to trauma or Scheurmann's disease, with appropriate
      selection of the surgical approach.

PMID- 15481420
TI  - Suction dressings in total knee arthroplasty--an alternative to deep suction
      drainage.
AB  - A new technique is described for dressing of surgical wounds in total knee
      arthroplasty that is a combination of a semi-permeable dressing and suction
      drainage. This technique has been used in 100 consecutive cases and drainage was
      collected in 92. The average volume was 198 ml (range 30 to 850 ml). There was no
      superficial or deep sepsis. Haematoma formation causing moderate soft tissue
      tension and some patient discomfort was noted in 9 knees. This form of
      postoperative wound management retains the nursing and hygiene advantages of deep
      suction drainage, whilst avoiding the patient discomfort and potential
      complication possibilities associated with deep internal drainage.

PMID- 15481421
TI  - The management of musculoskeletal infection in HIV carriers.
AB  - Over a three-year period, the authors prospectively implemented a protocol for
      management of musculoskeletal sepsis (MSS) in HIV carriers in Yaounde, Cameroon.
      The diagnosis of MSS was based on conventional criteria. HIV carriage was
      screened by an ELISA test and confirmed with the Western Blot technique. The
      immune status was based on CD4 lymphocyte count by flow cytometry; patients were
      classified as non-immunodepressed (NID), mildly immunodepressed (MID), or
      severely immunodepressed (SID) based on their CD4 lymphocyte count, as the latter
      was respectively over 500, between 200 and 500 or less than 200 per ml. Infection
      was treated by surgical debridement followed by a long-course targeted antibiotic
      therapy. All SID patients and some MID patients with AIDS-related symptoms also
      had standard antiretroviral (ARV) therapy. Thirty-one of 294 patients seen with
      musculoskeletal sepsis during the study period and tested for HIV were found to
      be HIV carriers. Their mean age was 33 years; the male/female ratio was 1.58. The
      following clinical pictures were observed: chronic osteomyelitis (COM) in 32.3%
      of the cases, septic arthritis (SA) in 38.7%, soft tissue infection (STI) in
      25.8%; the last case was a severe leg complication of Buruli Ulcer (BU). Among
      these 31 patients, 38.7% were classified as SID (5 COM, 4 SA, 2 STI and the BU
      patient), 25.8% as MID (2 COM, 4 SA, 2 STI) and 35.5% as NID (3 COM, 6 SA, 2
      STI). The organisms involved were not specific. Fifteen patients were managed
      conventionally, while the other 16 had the usual treatment associated with ARV
      therapy. The immediate outcome of MSS was good in 29 patients, after a mean
      hospital stay of five weeks; in two cases of septic arthritis of the knee, a
      second debridement was needed, due to persistent drainage, and the sinuses all
      closed. Three months after discharge, one patient with COM of the humerus
      developed a low-flow fistula which was closed after a revision sequestrectomy.
      After one year, none of the patients complained of any symptom suggesting
      reactivation of their MSS. There is no evidence that HIV carriage is in itself a
      high risk factor for musculoskeletal sepsis; the incidence of HIV carriage was
      indeed virtually similar in the 294 patients with MSS and in the general
      population, i.e. around 10%. However, in order to improve the outcome following
      musculoskeletal infections in patients with HIV, their management should take
      into account their immune status, based on a CD4 lymphocyte count. NID patients
      should be treated as any other patients with MSS, while SID should have
      additional standard ARV treatment. For those who are MID, the indication for
      antiretroviral therapy should depend on the presence of one or more AIDS-related
      signs.

PMID- 15481422
TI  - Minimally invasive intervention for acute bleeding from a pseudoaneurysm after
      revision hip arthroplasty.
AB  - After multiple revisions of her right hip arthroplasty, an 83-year-old woman
      developed deep infection with a chronic draining sinus. In August 2002 severe
      acute bleeding occurred through this fistula. Angiography revealed a
      pseudoaneurysm of the right external iliac artery. Because of the multiple
      pathologies affecting this ASA grade IV patient, conventional surgical treatment
      was considered to be contra-indicated, and a stent was placed percutaneously
      under fluoroscopic control to seal the vascular laceration. No haematoma and no
      further bleeding was observed on the control CT-scan or at angiography. However
      the patient died with terminal renal failure forty days later. The case reported
      shows a rare complication of total hip arthroplasty. The method used in this case
      to seal the leakage, using a covered stent, is uncommon but effective in cases
      where conventional surgery is contra-indicated.

PMID- 15481423
TI  - Phalangeal intraosseous epidermoid cyst.
AB  - The authors describe two cases of phalangeal intraosseous epidermoid cyst. Two
      theories try to explain their origin. One theory sees traumatic implantation of
      epidermal cells as causative. A second theory is based on faulty embryogenesis.

PMID- 15481424
TI  - Gouty flexor tenosynovitis mimicking infection: a case report emphasising the
      value of ultrasound in diagnosis.
AB  - Tenosynovitis of the flexor tendons of the hand is a rare manifestation of gout.
      We present an unusual case of gouty tenosynovitis mimicking infection. The role
      of ultrasound in the management of this condition is emphasised.

PMID- 15481425
TI  - Traumatic bilateral posterior dislocation of the hip--an unusual mechanism
      resulting from an agricultural accident.
AB  - Traumatic bilateral posterior dislocation of the hip is a rare injury, usually
      sustained in automobile accidents or less commonly in automobile-pedestrian
      accidents. An unusual mechanism of such an injury is reported in the setting of
      an agricultural accident: a heavy load fell on the pelvis of a farmer, while he
      was bending forward. This case highlights the importance of following health and
      safety guidelines at work, and above all common sense when working in hazardous
      situations.

PMID- 15481426
TI  - Congenital patellar aplasia in conjunction with trisomy 8. A case report.
AB  - Congenital patellar aplasia and hypoplasia are quite rare. Bilateral flexion
      deformity of the fifth finger, patellar aplasia in the right knee and patellar
      hypoplasia in the left knee were noted in a 6-year-old boy brought in for
      treatment of curvature of both little fingers. Active and passive movements of
      the knees were within normal range, and the quadriceps muscle was of normal
      strength. Trisomy 8 was determined on chromosome analysis. In contrast with the
      literature, the patellar abnormality was not concomitant with any other syndromes
      in our case, and most clinical findings of trisomy 8 were absent.

PMID- 15481427
TI  - A clunking knee with an unusual cause in an adolescent: a case report.
AB  - The authors report an unusual case of a chondral lesion in the knee joint in an
      adolescent. The lesion produced a clunk in the knee joint on flexion. A low
      resolution MRI scan failed to image the lesion. Arthroscopy revealed a unique
      shape of chondral flap from the weight bearing surface of the lateral femoral
      condyle, which resembled a meniscal bucket handle tear. Chondrectomy resolved all
      the symptoms. This case report highlights the point that special resolution MRI
      scan sequences are required to accurately assess these injuries and also that
      clunking in an adolescent can be produced by a chondral lesion.

PMID- 15481428
TI  - Osteoarthritis--a rare indication for atlantoaxial fusion. A case report and
      review of the literature.
AB  - The authors report a case of C1-C2 fusion which was performed in a 64-year-old
      woman with unilateral atlantoaxial osteoarthritis, who consulted because of
      incapacitating occipital pain and decreased cervical rotation without
      neurological deficit. The diagnosis of unilateral C1-C2 osteoarthritis was
      confirmed by an open-mouth radiograph, a bone-scan, a computerised tomography
      scan, and magnetic resonance imaging. C1-C2 fusion was performed using a computer
      assisted navigation system and posterior instrumentation. This resulted in marked
      relief of pain, and distinct improvement in quality of life. The prevalence of
      atlantoaxial osteoarthritis is about four per cent in patients suffering from
      peripheral or spinal osteoarthritis. However, many primary-care providers are not
      familiar with this entity. C1-C2 fusion remains rare, due to the difficulties
      related to the diagnosis of atlantoaxial osteoarthritis, its established non
      operative treatment options, and the fact that it has not received adequate
      attention in the orthopaedic literature. However, based on review of the
      literature, it can be stated that C1-C2 fusion is an effective and safe procedure
      providing distinct reduction of pain and increased quality of life in case of
      failure of conservative treatment.

PMID- 15481429
TI  - Nocardia farcinica arthritis of the knee. A case report.
AB  - Nocardia is a gram positive, aerobic branched actinomycete; it is an ubiquitous
      soil saprophyte. As an infecting agent it has been increasingly identified in
      humans, especially in immuno-suppressed hosts. Nocardia as a cause of septic
      arthritis is very unusual. The described genus was Nocardia asteroides in nearly
      all previously reported cases. We report an unusual case of spontaneous Nocardia
      farcinica septic arthritis of the left knee in a 68-year-old man, who was under
      systemic corticosteroids for chronic obstructive pulmonary disease. The diagnosis
      was rapidly made by Gram and acid-fast stains and later confirmed by culture. PCR
      was used to identify the subtype. The patient was treated successfully with
      sulphametaxazole-trimethoprim for six months. Our case re-emphasises, especially
      in the immuno-compromised patient, the importance of performing fungal and acid
      fast bacilli cultures, besides the most common bacterial cultures for aerobic and
      anaerobic organisms, in order to identify less common organisms and to initiate
      early and adequate treatment.

PMID- 15481430
TI  - The role of culturally competent communication in reducing ethnic and racial
      healthcare disparities.
AB  - Promoting culturally competent communication at the provider, care institution,
      health plan, and national levels is likely to contribute to success in reducing
      racial and ethnic disparities in the receipt of high quality care. Although some
      health plans recently have shown interest in addressing racial and ethnic
      disparities in care, very few have addressed how health plans can improve their
      cultural competency to reduce disparities. This commentary summarizes the
      importance of culturally competent communication across several levels of the
      healthcare system and details concrete steps that managed care organizations can
      take to maximize their ability to provide culturally competent communication and
      care.

PMID- 15481431
TI  - Healthcare disparities and models for change.
AB  - With Healthy People 2010 making the goal of eliminating health disparities a
      national priority, policymakers, researchers, medical centers, managed care
      organizations (MCOs), and advocacy organizations have been called on to move
      beyond the historic documentation of health disparities and proceed with an
      agenda to translate policy recommendations into practice. Working models that
      have successfully reduced health disparities in managed care settings were
      presented at the National Managed Health Care Congress Inaugural Forum on
      Reducing Racial and Ethnic Disparities in Health Care on March 10-11, 2003, in
      Washington, DC. These models are being used by federal, state, and municipal
      governments, as well as private, commercial, and Medicaid MCOs. Successful models
      and programs at all levels reduce health disparities by forming partnerships
      based on common goals to provide care, to educate, and to rebuild healthcare
      systems. Municipal models work in collaboration with state and federal agencies
      to integrate patient care with technology. Several basic elements of MCOs help to
      reduce disparities through emphasis on preventive care, community and member
      health education, case management and disease management tracking, centralized
      data collection, and use of sophisticated technology to analyze data and
      coordinate services. At the community level, there are leveraged funds from the
      Health Resources and Services Administration's Bureau of Primary Health Care.
      Well-designed models provide seamless monitoring of patient care and outcomes by
      integrating human and information system resources.

PMID- 15481432
TI  - Changing healthcare professionals' behaviors to eliminate disparities in
      healthcare: What do we know? How might we proceed?
AB  - The patient-healthcare provider communication process--particularly the
      provider's cultural competency--is increasingly recognized as a key to reducing
      racial/ethnic disparities in health and healthcare utilization. A working group
      was formed by the Office of Minority Health, Department of Health and Human
      Services to identify strategies for improving healthcare providers' cultural
      competency. This expert panel, one of several working groups called together to
      explore methods of reducing healthcare disparities, was comprised of individuals
      from academic medical centers and health professional organizations who were
      nationally recognized as having expertise in healthcare communication as it
      relates to diverse populations. During the 2-day conference, the panel
      identified, from personal experience and knowledge of the literature, key points
      of intervention and interventions most likely to improve the cross-cultural
      competency of healthcare providers. Proposed interventions included introduction
      of cultural competence education before, during, and after clinical training;
      implementation of certification and accreditation requirements in cross-cultural
      competence for practicing healthcare providers; use of culturally diverse
      governing boards for clinical practices; and active promotion of workforce cross
      cultural diversity by healthcare organization administrators. For each
      intervention, methods for implementation were specified. On-going monitoring and
      evaluation of processes of care using race/ethnicity data were recommended to
      ensure the programs were functioning.

PMID- 15481433
TI  - Good provider, good patient: changing behaviors to eliminate disparities in
      healthcare.
AB  - We examined the relationship between cross-cultural provider-patient interactions
      and health outcomes through a literature review. Results were presented in the
      form of guiding principles to an expert panel of health care administrators,
      medical practitioners, and medical care providers. This expert panel met at the
      workshop "Changing Patient Behavior" during a conference convened by the office
      of Minority Health, US Department of Health and Human Services, February 17-18,
      2000. The panel reviewed the themes and formulated suggestions for program and
      policy change. Six principles were identified: (1) Physicians should acknowledge
      that patients may be actively involved in health maintenance long before they
      seek medical care. (2) Patients should be empowered to be active participants in
      their medical care. (3) Providers should critically evaluate their own
      assumptions and underlying values about what constitutes a "good" patient and
      consider how these assumptions and values affect their communication strategies.
      (4) The patient's behavior change in the medical interaction should result from a
      process of negotiation between provider and patient. (5) The medical system
      should focus on community empowerment in addition to individual empowerment. (6)
      Accessible and understandable health outcome data will empower the community to
      participate in the elimination of health disparities.

PMID- 15481434
TI  - Providing linguistically appropriate services to persons with limited English
      proficiency: a needs and resources investigation.
AB  - Increasing numbers of persons in the United States cannot speak, read, write, or
      understand the English language at a level that permits them to interact
      effectively. These limitations can hamper encounters between patients and
      healthcare providers, often leading to misunderstandings as to diagnosis and
      treatment, which in turn may result in poor patient compliance, unsatisfactory
      outcomes, and increased costs. A questionnaire was developed and distributed to
      clinical practice managers at the University of Maryland School of Medicine to
      assess the needs for language interpretation services and resources among
      clinical faculty providing healthcare to persons with limited English proficiency
      (LEP). Literature review, search of key Web sites, and consultation with national
      experts on issues pertaining to language access, health services, and
      reimbursement strategies also were done. Then, recommendations regarding the
      costs and benefits of language interpretation in healthcare settings were
      developed. Because recipients of federal financial assistance from the Department
      of Health and Human Services must provide meaningful access to persons with LEP
      at no cost to the client, there are clear benefits to providing language
      interpretation. Providers and managers should be made aware of interpretation
      service options and cost-saving strategies.

PMID- 15481435
TI  - Cultural competency as it intersects with racial/ethnic, linguistic, and class
      disparities in managed healthcare organizations.
AB  - Culture in and of itself is not the most central variable in the patient-provider
      encounter. The effect of culture is most pronounced when it intersects with low
      education, low literacy skills, limited proficiency in English, culture-specific
      values regarding the authority of the physician, and poor assertiveness skills.
      These dimensions require attention in Medicaid managed care settings. However,
      the promise of better-coordinated and higher quality care for low-income and
      working-poor racial/ethnic populations--at a lower cost to government--has yet to
      be fully realized. This paper identifies strategies to reduce disparities in
      access to healthcare that call for partnerships across government agencies and
      between federal and state governments, provider institutions, and community
      organizations. Lessons learned from successful precedents must drive the
      development of new programs in Medicaid managed care organizations (MCOs) to
      reduce disparities. Collection of population-based data and analyses by race,
      ethnicity, education level, and patient's primary language are critical steps for
      MCOs to better understand their patients' healthcare status and improve their
      care. Research and experience have shown that by acknowledging the unique
      healthcare conditions of low-income racial and ethnic minority populations and by
      recruiting and hiring primary care providers who have a commitment to treat
      underserved populations, costs are reduced and patients are more satisfied with
      the quality of care.

PMID- 15481436
TI  - Distributive justice in American healthcare: institutions, power, and the
      equitable care of patients.
AB  - The authors argue that the American healthcare system has developed in a fashion
      that permits and may support ongoing, widespread inequities based on poverty,
      race, gender, and ethnicity. Institutional structures also contribute to this
      problem. Analysis is based on (1) discussions of a group of experts convened by
      the Office of Minority Health, US Department of Health and Human Services at a
      conference to address healthcare disparities; and (2) review of documentation and
      scientific literature focused on health, health-related news, language,
      healthcare financing, and the law. Institutional factors contributing to inequity
      include the cost and financing of American healthcare, healthcare insurance
      principles such as mutual aid versus actuarial fairness, and institutional power.
      Additional causes for inequity are bias in decision making by healthcare
      practitioners, clinical training environments linked to abuse of patients and
      coworkers, healthcare provider ethnicity, and politics. Recommendations include
      establishment of core attributes of trust, relationship and advocacy in health
      systems; universal healthcare; and insurance systems based on mutual aid. In
      addition, monitoring of equity in health services and the development of a set of
      ethical principles to guide systems change and rule setting would provide a
      foundation for distributive justice in healthcare. Additionally, training centers
      should model the behaviors they seek to foster and be accountable to the
      communities they serve.

PMID- 15481437
TI  - Epigenetic system: a pathway to malignancies and a therapeutic target.
AB  - Cancer cells possess both genetic and epigenetic alterations that dysregulate
      essential cellular processes, leading to disordered cell proliferation and
      differentiation. Oncogenes and tumor suppressor genes have been found to be
      activated and inactivated, respectively, in malignant cells. Epigenetic
      regulation of the genome is mediated by interactions between DNA methylation,
      chromatin, and modifications of histones and various transcriptional regulators.
      Recent studies have shown that some components of the epigenetic system as well
      as epigenetically mutated genes are diagnostic and therapeutic targets in cancer.
      We discuss the molecular basis of the epigenetic mechanism in association with
      the development of cancer.

PMID- 15481439
TI  - Beyond genetics--the emerging role of epigenetic changes in hematopoietic
      malignancies.
AB  - The term epigenetic refers to a heritable change in gene expression that is
      mediated by mechanisms other than alterations in the primary nucleotide sequence.
      DNA methylation at cytosine bases that are located 5' to guanosine within a CpG
      dinucleotide is the main epigenetic modification in humans. Patterns of DNA
      methylation are profoundly deranged in human cancer and comprise genome-wide
      losses as well as regional gains in DNA methylation. Hypermethylation of CpG
      islands within gene promoter regions is associated with transcriptional
      inactivation and represents, in addition to genetic aberrations, an important
      mechanism of gene silencing in the pathogenesis of hematopoietic malignancies.
      This epigenetic phenomenon acts as an alternative to mutations and deletions to
      disrupt tumor suppressor gene function. A large number of genes involving
      fundamental cellular pathways may be affected in virtually all types of human
      cancer by aberrant CpG island methylation in association with transcriptional
      silencing. Altered methylation patterns can be used as biomarkers for cancer
      detection, assessment of prognosis, and prediction of response to antitumor
      treatment. Furthermore, clinical trials using epigenetically targeted therapies
      have yielded promising results for acute and chronic leukemias as well as for
      myelodysplastic syndromes. The exploration of our growing knowledge about
      epigenetic aberrations may help develop novel strategies for the diagnosis and
      treatment of hematopoietic malignancies in the future.

PMID- 15481440
TI  - DNA methylation as a therapeutic target in hematologic disorders: recent results
      in older patients with myelodysplasia and acute myeloid leukemia.
AB  - DNA methylation provides a major epigenetic code (besides histone modification)
      of the lineage- and development-specific genes (such as regulators of
      differentiation in the hematopoietic lineages) that control expression of normal
      cells. However, DNA methylation is also involved in malignancies because aberrant
      methylating gene activity occurs during leukemic transformation. Thus, genes such
      as tumor suppressor genes, growth-regulatory genes, and adhesion molecules are
      often silenced in various hematopoietic malignancies by epigenetic inactivation
      via DNA hypermethylation. This inactivation is frequently seen not only in
      transformed cell lines but also in primary leukemia cells. Because this defect is
      amenable to reversion by pharmacologic means, agents that inhibit DNA methylation
      have been developed to specifically target this hypermethylation defect in
      leukemia and preleukemia cases. The most clinically advanced agents, the
      azanucleosides 5-azacytidine and 5-aza-2'-deoxycytidine (decitabine), were
      discovered more than 25 years ago, when their methylation-inhibitory activities,
      even at low concentrations, became apparent. Although both of these agents, like
      cytarabine, had been clinically used until then at high doses, the redevelopment
      of these agents for low-dose schedules has revealed very interesting clinical
      activities for treating myelodysplasia (MDS) and acute myeloid leukemia (AML).
      Because these diseases occur mostly in patients over 60 years of age, low-dose
      schedules with these compounds provide a very promising approach in such patient
      groups by virtue of their low nonhematologic toxicity profiles. In the present
      review, we describe the development of treatments that target DNA
      hypermethylation in MDS and AML, and clinical results are presented. In addition,
      pharmacologic DNA demethylation may be viewed as a platform for biological
      modification of malignant cells to become sensitized (or resensitized) to
      secondary signals, such as differentiating signals (retinoids, vitamin D3) and
      hormonal signals (eg, estrogen receptor in breast cancer cells, androgen receptor
      in prostate cancer cells). Finally, an in vitro synergism between the
      reactivating potency of demethylating agents and inhibitors of histone
      deacetylation has been tested in several pilot studies of AML and MDS treatment.
      Finally, gene reactivation by either group of compounds results in
      therapeutically meaningful reactivation of fetal hemoglobin in patients with
      severe hemoglobinopathies, extending the therapeutic range of derepressive
      epigenetic agents to nonmalignant hematopoietic disorders.

PMID- 15481441
TI  - Hemoglobin Pakse: presence on red blood cell membrane and detection by polymerase
      chain reaction-single-strand conformational polymorphism.
AB  - Nondeletional gene mutations giving rise to alpha-thalassemia can be found at
      polymorphic frequency in Southeast Asia. Although the most common is hemoglobin
      Constant Spring (Hb CS), caused by a termination codon mutation (UAA --> CAA,
      Gln) in the alpha2-globin gene and resulting in reduced synthesis of the
      elongated alpha-globin variant, Hb Pakse (UAA --> UAU, Tyr) also has been
      observed at a significant prevalence. Western blot analysis of ghost membrane
      proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      from an individual with alpha-thal 1/Hb Pakse revealed the existence of a higher
      molecular weight globin of 18 kd consistent with an alpha(Pakse)-globin chain.
      The presence of alpha(Pakse)-globin on membranes of Hb Pakse-containing red blood
      cells affords an explanation for the severity of anemia observed in such
      patients. However, because the 2 Hb variants cannot be distinguished by current
      biochemical techniques, we developed a convenient single-tube polymerase chain
      reaction-single-strand conformational polymorphism (PCR-SSCP) protocol for the
      simultaneous diagnosis of Hb CS and Hb Pakse by amplifying a short fragment
      covering the termination codon of the alpha2-globin gene. This PCR-SSCP method
      required no internal control coamplification or use of restriction enzymes and
      has the potential of identifying all the other possible termination codon
      mutations in a single reaction with only 1 pair of primers.

PMID- 15481438
TI  - Epigenetic inactivation of tumor suppressor genes in hematologic malignancies.
AB  - A number of genetic alterations are involved in the development of hematologic
      malignancies. These alterations include the activation of oncogenes by
      chromosomal translocation or gene amplification and the inactivation of tumor
      suppressor genes by gene deletion or mutations. Recently, epigenetic change has
      been proven to be another important means of inactivating tumor suppressor genes
      in tumor cells, and hypermethylation of promoter DNA is one of the most important
      mechanisms. In hematologic malignancies, many kinds of tumor suppressor genes and
      candidate suppressor genes are epigenetically inactivated. Inactivation of tumor
      suppressor genes usually occurs in a disease-specific manner and plays important
      roles in the development and progression of the disease. Some of these
      alterations have clinical effects on treatment results or the prognoses of the
      patients.

PMID- 15481442
TI  - Simultaneous demonstration of clonal chromosome abnormalities and apoptosis in
      individual marrow cells in myelodysplastic syndrome.
AB  - Bone marrow samples from 18 patients with myelodysplastic syndrome (MDS) with
      clonal cytogenetic abnormalities were characterized by combining fluorescence in
      situ hybridization (FISH) with in situ end-labeling (ISEL) or with annexin V
      staining and flow cytometry (AV/FLOW) to determine the clonal nature of
      hematopoietic cells undergoing apoptosis in marrow cells. Apoptosis occurred in
      both normal and clonal cells. However, the proportion of clonal cells identified
      by FISH among apoptotic cells was lower than the proportion among nonclonal cells
      in 17 of 18 patients, regardless of whether ISEL or AV/ FLOW was used to identify
      apoptosis. This technique allows us to identify simultaneously clonality (as
      determined by FISH) and apoptosis in individual cells and shows that although
      apoptosis occurs predominantly in residual normal (FISH-negative) cells, a
      proportion of clonal precursors in MDS marrow also die from programmed cell
      death. Such a mechanism may be responsible for the generally slow expansion of
      the clone in MDS.

PMID- 15481443
TI  - Increased levels and activity of E2F1 transcription factor in myelodysplastic
      bone marrow.
AB  - The bone marrow of patients with myelodysplastic syndromes (MDS) shows excessive
      intramedullary apoptosis, particularly in S-phase cells. In the light of previous
      reports that showed a link between experimental overexpression of the E2F1
      transcription factor and apoptosis in the S phase, we compared the status of E2F1
      protein in bone marrow mononuclear cells of MDS patients with that of healthy
      donors. Nearly 67% of MDS marrow samples showed higher expression of E2F1
      transcription factor than in healthy donors. The retinoblastoma gene product, Rb,
      is a major negative regulator of E2F1 activity; however, Rb protein levels were
      found to be normal in MDS marrow samples. Amplification of genomic DNA by the
      polymerase chain reaction (PCR) showed no E2F1 gene amplification or mutation in
      the Rb-binding region of E2F1 in MDS patients, nor was transcriptional up
      regulation noted when E2F1 messenger RNA (mRNA) levels were estimated with real
      time reverse transcriptase-PCR. Furthermore, the overexpression of E2F1 was
      paralleled by its increased transcriptional activity, as reflected by the
      increased mRNA levels for one of its target genes, dihydrofolate reductase.
      Importantly, in a subset of the studied MDS patients for whom a simultaneous
      measurement of apoptosis in S-phase cells was possible, the E2F1 protein levels
      showed a significant positive correlation with this phenomenon. Previously,
      increased E2F1 activity in human disease had been found primarily as a
      consequence of Rb derailment. Hence, the observation in MDS of increased E2F1
      activity in the presence of normal Rb levels is novel and unique, and E2F1
      activity in association with apoptosis in S-phase cells may thus have significant
      therapeutic implications.

PMID- 15481445
TI  - Possibility of the diagnosis of subacute myeloid leukemia for a group of patients
      with trisomy 8: a report of 34 cases.
AB  - The term subacute myeloid leukemia is not present in most hematologic textbooks,
      but clinically the disease does exist. During the past 13 years, 34 patients with
      trisomy 8 (+8) and previous diagnoses of refractory anemia with excess blasts in
      myelodysplastic syndromes were followed and studied in our institute. None of the
      patients had been given cytotoxic drugs before the leukemia became apparent.
      Eighteen patients (52.9%) had a history of 3 months to more than 20 years before
      cytogenetic detection of +8. Abnormalities of blood cell counts were seen in 1 to
      3 cell lines, with a median blast cell percentage in the bone marrow of 8%
      (range, 5%-19%). At a median follow-up period of 21.5 months (range, 3-129
      months), the median overall survival time was 20 months for all of the patients
      with +8, including the patients with chromosome abnormalities in addition to +8.
      In the group with +8 only, 11 (45.8%) of the 24 patients developed frank
      leukemia, and 9 of these 11 patients died. In conclusion, our results showed that
      this group of +8 patients had multilineage abnormalities in blood cell counts and
      increased numbers of blasts in the bone marrow. The diseases of these patients
      manifested an insidious onset and a subacute but progressive clinical course, and
      they all had cytogenetic clonal changes with +8. These facts suggest that this
      group of +8 patients all had evidence of a leukemic clone, and their conditions
      might conform to the diagnosis of subacute myeloid leukemia.

PMID- 15481444
TI  - Fluorescent in situ hybridization analysis of Philadelphia chromosome-negative
      chronic myeloid leukemia with the bcr/abl fusion gene.
AB  - This report describes a patient with Philadelphia chromosome-negative (Ph-) but
      bcr/abl fusion gene-positive chronic myeloid leukemia (CML) and a molecular
      analysis of the mechanisms behind the Ph status. Spectral karyotyping-fluorescent
      in situ hybridization (SKY-FISH) analysis showed no abnormal translocation;
      however, a bcr/abl fusion gene was detected by reverse transcriptase-polymerase
      chain reaction analysis. FISH analysis showed that signals from the 9q and 22q
      subtelomere probes were detected on the der(9) and der(22) chromosomes,
      respectively. On the other hand, FISH analysis of the abl and bcr genes with dual
      fusion probes, which can detect the bcr/abl fusion gene on both the der(9) and
      der(22) chromosomes, showed the signal for bcr/abl fusion on the der(22)
      chromosome but not on the der(9) chromosome. These results indicate that
      insertion of the abl gene into the bcr region on the der(22) chromosome or
      retranslocation between the der(9) chromosome and the der(22) chromosome may have
      caused the Ph CML in this case.

PMID- 15481446
TI  - Acute respiratory distress syndrome during the third infusion of rituximab in a
      patient with follicular lymphoma.
AB  - We present the case of a 66-year-old man with follicular lymphoma who developed
      acute respiratory distress syndrome (ARDS) during a third infusion of rituximab.
      High fever, tachypnea, and progressive hypoxemia accompanied by massive bilateral
      pleural effusions appeared suddenly approximately 3 hours after the third
      infusion was started, although the 2 prior infusions of rituximab had produced
      only mild adverse effects. The patient was treated successfully with high-dose
      methylprednisolone and 3 days of mechanical ventilatory support. No evidence was
      obtained to indicate that the ARDS had been caused by either cytokine release or
      tumor lysis, and serum human antichimeric antibody was not detected. Although the
      cause of ARDS was not confirmed, our experience in this case suggested that an
      anaphylactic reaction induced by repeated infusion of rituximab was involved in
      the onset of pulmonary disease. Although ARDS is rarely seen with rituximab
      infusion, careful management is required for safe administration of the newly
      developed rituximab therapy. This management includes monitoring biological
      reactions not only during the initial infusion but also during subsequent
      infusions of the antibody.

PMID- 15481447
TI  - Peripheral blood stem cell collection after intermediate-dose cytarabine in adult
      patients with acute myeloblastic leukemia undergoing autologous blood stem cell
      transplantation in first complete remission.
AB  - Different strategies for collecting peripheral blood stem cells (PBSC) for
      autologous blood stem cell transplantation (ABSCT) have been reported for
      patients with acute myeloblastic leukemia (AML). We compared the clinical results
      of 2 consecutive protocols in 75 adult patients with AML in first complete
      remission who underwent ABSCT. In the first 56 patients (group A), PBSC were
      collected after induction and/or consolidation chemotherapy courses. In the
      subsequent 19 patients (group B), PBSC collection was done after a further
      intensification course with intermediate-dose cytarabine and mitoxantrone.
      Hematopoietic engraftment was similar in the 2 groups, with the median times to
      reach 0.5 x 10(9) neutrophils/L and 20 x 10(9) platelets/L being 13 days each in
      group A, and 12 days and 24 days, respectively, in group B. There were 3 graft
      failures (all in group A) and 5 transplantation-related deaths (6.6%, 4 in group
      A and 1 in group B). Although not statistically significant, the 3-year
      probabilities of both relapse (31% versus 66%; P = .12) and disease-free survival
      (60% versus 36%; P = .1) compared favorably for group B. Our study suggests that
      collection of PBSC after additional intensification can result in a better
      outcome for AML patients who undergo ABSCT.

PMID- 15481449
TI  - Primary myelofibrosis terminated in basophilic leukemia and successful allogeneic
      bone marrow transplantation.
AB  - Transformation of primary myelofibrosis (PMF) to basophilic leukemia is very
      rare. We report the case of a 44-year-old man who had had PMF for 6 years. His
      hematopoiesis deteriorated with marked splenomegaly, requiring multiple red blood
      cell and platelet transfusions. Soon after splenectomy, progressive basophilia
      (32.3 x 10(9)/L) developed, infiltrating the skin as well as the bone marrow. The
      patient underwent allogeneic bone marrow transplantation with cells from an HLA
      matched sibling. Despite the presence of hyperhistaminemia (99.1 ng/mL) after
      conditioning with cyclophosphamide, the pregrafting and post-grafting periods
      were uneventful. Prophylactic administration of both H1 and H2 receptor
      antagonists and sufficient hydration appeared to be important.

PMID- 15481448
TI  - Unrelated donor marrow transplantation for congenital immunodeficiency and
      metabolic disease: an update of the experience of the Japan Marrow Donor Program.
AB  - We retrospectively analyzed the clinical results of 81 patients with congenital
      genetic diseases who were treated with bone marrow transplantation (BMT) from
      unrelated donors identified through the Japan Marrow Donor Program. The patients
      were aged between 1 and 38 years (median, 4 years). Thirty-five patients
      underwent transplantation for metabolic disease (MD), ie, mucopolysaccharidosis
      (n = 25), adrenoleukodystrophy (n = 7), and others (n = 3). The remaining 46
      patients had Wiskott-Aldrich syndrome (n = 16), hemophagocytic syndrome including
      the inherited type (n = 9), severe combined immunodeficiency (n = 6), hyper-IgM
      syndrome (n = 4), Chediak-Higashi syndrome (n = 3), Kostmann syndrome (n = 3),
      and others (n = 5). Fifty-two donor-patient pairs were fully matched at HLA-A,
      HLA-B, and HLA-DRB1 alleles. The remaining 24 patients received allele-mismatched
      grafts (20 matched at 5 of 6 loci and 4 matched at 4 of 6 loci). Engraftment
      occurred in 82.4% of the MD group and 90.7% of the other genetic disease (OGD)
      group; however, 14 patients (18.2%) experienced either early or late graft
      failure. The cumulative incidence of grade II to IV acute graft-versus-host
      disease (GVHD) was 35.5% - 9.8% in the MD group and 47.3% - 9.5% in the OGD
      group, and the rate of chronic GVHD was 20% in both groups. Forty-nine patients
      have survived for 3 to 96 months (median, 20 months). The probabilities of 5-year
      overall survival and event-free survival were 72.6% - 11.5% and 65.3% - 8.6%,
      respectively, for MD (n = 35) and 72.5% - 7.3% and 63.6% - 7.3% for OGD (n = 46).
      Although patient status before BMT and the occurrence of grade III to IV acute
      GVHD significantly affected outcome, unrelated BMT is a curative therapeutic
      option for children with congenital genetic diseases who have no HLA-matched
      family donors.

PMID- 15481451
TI  - Successful allogeneic bone marrow transplantation in a patient with acute
      myelogenous leukemia and cytomegalovirus retinitis.
AB  - A 1-year-old boy with acute myeloid leukemia with cytomegalovirus (CMV) retinitis
      that was refractory because of severely impaired cellular immunity underwent bone
      marrow transplantation from an HLA-matched donor after a conditioning regimen of
      busulfan, cyclophosphamide, and etoposide. Although we continued administration
      of ganciclovir from preparation therapy, retinitis worsened after engraftment.
      Thereafter retinitis improved gradually as the number of CD4+ T-lymphocytes
      increased. The findings in this case suggest that stem cell transplantation for a
      leukemia patient with CMV disease may be effective.

PMID- 15481450
TI  - Granulocytic sarcoma presenting with severe adenopathy (cervical lymph nodes,
      tonsils, and adenoids) in a child with juvenile myelomonocytic leukemia and
      successful treatment with allogeneic bone marrow transplantation.
AB  - The occurrence of adenopathy in patients with myelodysplastic syndrome-associated
      extramedullary myeloid cell tumors has rarely been reported. We describe a 7-year
      old girl with juvenile myelomonocytic leukemia who showed the novel chromosomal
      abnormality t(9;12)(p22;q24.1) and who developed severe adenopathy of the
      cervical lymph nodes, tonsils, and adenoids that was manifested as granulocytic
      sarcoma. Following chemotherapy, the patient underwent a conditioning regimen of
      busulfan, cyclophosphamide, and total body irradiation followed by successful
      allogeneic bone marrow transplantation from her single HLA locus-mismatched
      mother at 6 months after her diagnosis. The patient continues to be well and in
      remission 3 years after stem cell transplantation.

PMID- 15481452
TI  - Bone marrow expression and plasma concentration of basic fibroblast growth factor
      in patients with idiopathic thrombocytopenic purpura.
AB  - BACKGROUND: Basic fibroblast growth factor (bFGF) is one of main regulators of
      hematopoiesis, including megakaryopoiesis. The main bone marrow finding of
      patients with idiopathic thrombocytopenic purpura (ITP) is increased
      megakaryopoiesis. The purposes of this study were to evaluate the change in the
      production of bFGF and its expression pattern in the bone marrow of patients with
      ITP and to correlate these characteristics with the plasma concentration of bFGF.
      METHODS: Paraffin sections of bone marrow biopsies from 17 patients with ITP and
      5 healthy control subjects without pathologic alterations were investigated by
      immunohistochemistry for bFGF and CD68. bFGF messenger RNA (mRNA) in situ
      hybridization was performed with bone marrow biopsy sections, and the plasma
      levels of bFGF were evaluated by enzyme immunoassay. RESULTS: bFGF was expressed
      strongly in stromal cells and weakly in megakaryocytes. The density of bFGF
      expressing stromal cells was decreased in 70% (12/17) of the patients with ITP
      but in none of the control subjects. The numbers of stromal cells and the
      cellular distributions of bFGF mRNA in patients with ITP were similar to those of
      the control subjects. The plasma levels of bFGF were significantly lower in
      almost all of the ITP patients relative to those of the control group.
      CONCLUSIONS: The results indicate that the concentrations of bFGF in plasma and
      bone marrow stromal cells in ITP cases are decreased, whereas the production of
      bFGF remains unchanged. Although the mechanism of low cellular and plasma
      concentrations of bFGF needs to be elucidated, these findings may complement the
      serologic and morphologic diagnosis of ITP.

PMID- 15481453
TI  - DIDMOAD syndrome: a diagnostic as well as therapeutic dilemma.

PMID- 15481454
TI  - Epstein-Barr virus-positive Hodgkin's lymphoma in a patient with chronic active
      Epstein-Barr virus infection.

PMID- 15481455
TI  - Parts per quadrillion level ultra-trace determination of polar and nonpolar
      compounds via solvent-free capillary microextraction on surface-bonded sol-gel
      polytetrahydrofuran coating and gas chromatography-flame ionization detection.
AB  - Sol-gel polytetrahydrofuran (poly-THF) coating was developed for high-sensitivity
      sample preconcentration by capillary microextraction (CME). Parts per quadrillion
      (ppq) level detection limits were achieved for both polar and nonpolar analytes
      through sample preconcentration on sol-gel poly-THF coated microextraction
      capillaries followed by gas chromatography (GC) analysis of the extracted
      compounds using a flame ionization detector (FID). The sol-gel coating was in
      situ created on the inner walls of a fused silica capillary using a sol solution
      containing poly-THF as an organic component, methyltrimethoxysilane (MTMOS) as a
      sol-gel precursor, trifluoroacetic acid (TFA, 5% water) as a sol-gel catalyst,
      and hexamethyldisilazane (HMDS) as a deactivating reagent. The sol solution was
      introduced into a hydrothermally-treated fused silica capillary and the sol-gel
      reactions were allowed to take place inside the capillary for 60 min. A wall
      bonded coating was formed due to the condensation of silanol groups residing on
      the capillary inner surface with those on the sol-gel network fragments evolving
      in close vicinity of the capillary walls. Poly-THF is a medium polarity polymer,
      and was found to be effective in carrying out simultaneous extraction of both
      polar and nonpolar analytes. Efficient extraction of a wide range of trace
      analytes from aqueous samples was accomplished using sol-gel poly-THF coated
      fused silica capillaries for further analysis by GC. The test analytes included
      polycyclic aromatic hydrocarbons (PAHs), aldehydes, ketones, chlorophenols, and
      alcohols. To our knowledge, this is the first report on the use of a poly-THF
      based sol-gel material in analytical microextraction. Sol-gel poly-THF coated CME
      capillaries showed excellent solvent and thermal stability (>320 degrees C).

PMID- 15481456
TI  - Development of solid-phase extraction and solid-phase microextraction methods for
      the determination of chlorophenols in cork macerate and wine samples.
AB  - Tri-, tetra- and pentachlorophenol (TCP, TeCP and PCP) can be considered the
      precursors in the formation of corresponding chloroanisoles, known to be powerful
      odorants in corks and wine. Determining the presence of these chlorophenolic
      compounds in cork soaking solutions (ethanol/water mixtures, 12% (v/v) ethanol
      used for cork quality control testing), or in wine can be achieved by
      acetylation/gas chromatography electron-capture detection. In order to reach the
      required sensitivity, a previous preconcentration step is necessary. Solid-phase
      extraction (SPE) and headspace solid-phase microextraction (HS-SPME) have given
      good results for the preconcentration of TCP, TeCP and PCP in such matrices. The
      use of Oasis HLB cartridges gives acceptable recoveries for the three compounds
      when different volumes (50-250 mL) of cork macerate with concentrations ranging
      from 20 to 150 ng/L are processed. Preconcentration based on HS-SPME has also
      been optimised with a 100 microm polydimethylsiloxane fibre and in situ
      derivatization. The HS-SPME method allows chlorophenols in a cork soaking
      solution and in wine to be determined with a limit of detection of 1 ng/L for
      each compound (in cork macerate) and a repeatability of around 0.5%-5% (n=8) for
      a concentration level of 30 ng/L.

PMID- 15481457
TI  - Transportable frontal chromatographic unit for decontamination purposes based on
      the twin column concept.
AB  - The design and operation of a separation unit based on frontal chromatography is
      described. The important feature of the design is the array column --> detector -
      > column which allows process monitoring below the detection limits of the
      monitor. By using "fraternal twin columns" an in-process calibration of the
      detector is achieved reducing the waste production. The design contains
      provisions for on-line destructive and non-destructive monitoring. Tests of the
      unit prove its versatility with respect to decontamination processes. Due to its
      compactness, the unit is transportable, if not portable, and the module
      construction allows easy posting and set-up in areas with restricted access. The
      unit is capable of processing up to 5 m3 solution per year depending on the
      chemical system used.

PMID- 15481458
TI  - Effect of the ionic strength of the solution and the nature of its ions on the
      adsorption mechanism of ionic species in RPLC III. Equilibrium isotherms and
      overloaded band profiles on Kromasil-C18.
AB  - In two companion papers, we have described the influence of the concentration and
      the nature of completely dissociated salts dissolved in the mobile phase
      (methanol:water, 40:60, v/v) on the adsorption behavior of propranolol (R'-NH2+
      R, Cl-) on XTerra-C18 and on Symmetry-C18. The same experiments were repeated on
      a Kromasil-C18 column to compare the adsorption behavior of this ionic compound
      on these three different RPLC systems. The adsorption data of propranolol
      hydrochloride were first measured by frontal analysis (FA) using a mobile phase
      without salt. These data fit best to the Bi-Moreau model. Large concentration
      band profiles of propranolol were recorded with mobile phases containing
      increasing KCl concentrations (0, 0.002, 0.005, 0.01, 0.05, 0.1 and 0.2 M) and
      the best values of the isotherm coefficients were determined using the numerical
      solution of the inverse problem of chromatography. The general effect of a
      dissociated salt in the mobile phase was the same as the one observed earlier
      with XTerra-C18 and Symmetry-C18. However, obvious differences were observed for
      the shape of the band profiles recorded at low column loading (1.5 g/L, 250
      microL injected). A long shoulder is visible at all salt concentrations and the
      band broadening is maximum at low salt concentrations. A slow mass transfer
      kinetics on the high-energy sites of the bi-Moreau model might explain this
      original shape. Five other salts (NaCl, CsCl, KNO3, CaCl2 and Na2SO4) were also
      used at the same ionic strength (J = 0.2 M). As many different band profiles were
      observed, suggesting that specific solute-salt interactions take place in the
      adsorbed phase.

PMID- 15481459
TI  - Capillary high-performance liquid chromatography-electrospray ionization mass
      spectrometry using monolithic columns and carbon fiber electrospray ionization
      emitters.
AB  - Monolithic columns having long hydrocarbon chains were prepared by in-situ
      polymerization in capillary fused silica tubing. The capillary columns were
      coupled with a newly developed carbon fiber electrospray ionization (ESI) emitter
      for proteomic analysis using sheathless capillary HPLC-ESI mass spectrometry
      (MS). The sample loading capacity and chromatographic performance of the styrene
      based monolithic column, which was prepared by photo-polymerization of
      octylstyrene (OS) and divinylbenzene (DVB) were compared with that of the
      methacrylate-based monolithic column composed of lauryl methacrylate (LMA) and
      ethylene dimethacrylate (EDMA). The sample loading ability of tryptic digested
      protein in poly-OS (POS)-DVB column was higher than that of poly-LMA (PLMA)-EDMA
      column, possibly due to the irregular and rugluous surface offering a greater
      surface area of POS-DVB stationary phase. The POS-DVB column also provided better
      separation efficiency in the separation of high concentration (10 microg) of
      tryptic digested albumin bovine serum (BSA). Due to the successful interface of a
      highly efficient monolithic column and a stable, durable carbon fiber emitter,
      low femtomole levels of peptides were successfully separated and identified in
      the presence of large amounts of tryptic digested protein.

PMID- 15481460
TI  - Liquid chromatographic enantiomer separations of novel quinazolone derivatives on
      quinine carbamate based chiral stationary phases using hydro-organic mobile
      phases.
AB  - Quinine carbamate-type weak chiral anion-exchange selectors (SOs) and the
      respective chiral stationary phases (CSPs) have been used for the direct liquid
      chromatographic enantiomer separation of a wide range of chiral acids. In the
      present work, we demonstrate that these CSPs can also be extended to chiral
      discrimination of a set of neutral polar potential NMDA (N-methyl-D-aspartic
      acid) and/or AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)
      antagonist imidazo-quinazoline-dione derivatives (selectands, SAs) using
      acetonitrile and methanol containing hydro-organic and buffered mobile phases.
      The influence of mobile phase composition, column temperature and structure
      variation of the SAs and SOs on retention and enantioselectivity was
      systematically investigated to gain insight into the overall chiral recognition
      mechanism. As was expected for the reversed-phase mode, acetonitrile has a
      stronger eluotropic effect compared to methanol. Except for two analytes, the
      acetonitrile containing mobile phases provided baseline resolution (R(S)) of the
      enantiomers with R(S) values ranging between 1.68 and 2.76. Using methanol as the
      organic modifier enhanced the enantioselectivity. The enthalpic and entropic
      terms for the SO-SA association were calculated from the linear van't Hoff plots.
      Data reveal that the enantiomer separations are predominantly enthalpically
      driven.

PMID- 15481461
TI  - First European interlaboratory study of the analysis of benzoxazinone derivatives
      in plants by liquid chromatography.
AB  - Six laboratories from four different countries participated in the first European
      interlaboratory comparison exercise within the framework of the "Fate and
      toxicity of allelochemicals (natural plant toxins) in relation to environment and
      consumer" (FATEALLCHEM) European Union Project. The study, organized between
      November 2002 and March 2003, involved the analyses of seven benzoxazinone
      derivatives in two standard solutions and one purified extract of root material.
      Results are reported from the first phase of the study that examined the
      variability associated with different detection methods and different
      laboratories. The analytical strategies were based on liquid chromatography (LC)
      with diode array detection, LC coupled to mass spectrometry (MS) and LC coupled
      to tandem MS. When data from all laboratories were pooled, the relative standard
      deviation values ranged from 2 to 14% for the determination of target compounds
      in standard solutions, and between 19 and 47% for the analysis in root material.
      Comparison of the three detection techniques leads to the conclusion that MS
      approaches are the most accurate and precise techniques for the determination of
      benzoxazinone derivatives at ng/microL level in plant material.

PMID- 15481462
TI  - Separation and quantification by high-performance liquid chromatography with
      light scattering detection of the main wheat flour phospholipids during dough
      mixing in the presence of phospholipase.
AB  - Phospholipids (PL) are minor components of wheat flour involved in baking quality
      and exogenous phospholipids are used as emulsifiers giving better loaf volume and
      crumb grain. Few biochemical data are available on the phospholipid evolution
      during mixing, probably because of the time-consuming methods proposed for their
      extraction, separation and quantification. In the present study, the extraction,
      separation and quantification of the main wheat flour phospholipids were carried
      out. Total lipids (2% dry mass of wheat flour) were extracted from flour or dough
      by a mixture of chloroform-methanol-water (1:1:1 (v/v)). The phospholipids were
      separated from the lipid extract on silica cartridge by solid-phase extraction
      (SPE) procedure under a 1.5-4 mmHg vacuum, at a 0.8 mL min(-1) flow rate (1 mmHg
      = 133.322 Pa). The recovery of the lipid extract was 100%, whereas the SPE yield
      for the PLs was 50%. The resulting fraction was then submitted to HPLC with
      evaporative light scattering detection on a Diol stationary phase allowing the
      separation and quantification of each class of phospholipids, in less than 16
      min. The developed method allowed to quantify the phospholipid amounts from eight
      wheat flours as well as their evolution during mixing in the presence of
      phospholipase.

PMID- 15481463
TI  - Quantitative analysis of twelve sulfonamides in honey after acidic hydrolysis by
      high-performance liquid chromatography with post-column derivatization and
      fluorescence detection.
AB  - A quantitative HPLC-fluorescence method for the simultaneous determination of 12
      sulfonamides (sulfaguanidine, sulfanilamide, sulfacetamide, sulfadiazine,
      sulfathiazole, sulfapyridine, sulfamerazine, sulfamether, sulfamethazine,
      sulfamethoxypyridazine, sulfachloropyridazine and sulfadoxine) in honey was
      developed and validated. Sample pretreatment included acidic hydrolysis, followed
      by liquid-liquid extraction and solid-phase extraction on a strong cation
      exchanger. LC separation was performed in 45 min, with a total analysis time of
      60 min. Identification and quantitation were based on retention time and
      fluorescence intensity, respectively. Peak area ratios of the target analytes and
      the internal standard were fit to a linear least-squares regression curve with a
      weighting factor of 1/x. Limits of detection and quantitation (LOQ) had values of
      1 or 2 and 2 or 5 ng/g, respectively. Linearity was obtained with an average
      coefficient of determination (R2) higher than 0.997, over a dynamic range from
      the LOQ value up to 100ng/g. The method demonstrated good intra- and interbatch
      precision and accuracy. No interferences with the peaks of interest were observed
      throughout the chromatographic run. Sample pretreatment provided efficient
      cleanup, while post-column derivatization with fluorescamine proved to be a
      reproducible derivatization technique enabling a sensitive and rugged
      quantitative determination of sulfonamides.

PMID- 15481464
TI  - Ultra thick film open tubular traps with an increased inner diameter.
AB  - In this paper, the concept of open tubular traps, coated with a very thick film
      of polydimethyldisiloxane for enrichment of trace volatile components has been
      further explored. From theoretical calculations as well as practical experiments
      it is demonstrated that it can be advantageous to increase the inner diameter of
      such traps. For a given sampling flow rate and phase ratio, the plate number of
      the traps is not dependent on the inner diameter, provided that the linear flow
      velocity remains sufficiently high to offset the effect of axial diffusion. It is
      shown that this is due to the basic fact that for a given sampling flow rate, the
      average linear flow velocity in the trap is inversely proportional to the square
      of the inner diameter of the trap. However, in contrast to chromatographic
      separations, the linear flow velocity is not important. Under conditions of a
      constant phase ratio, an increased inner diameter also increases the amount of
      sorbent in the trap, which is a key parameter for obtaining high breakthrough
      volumes. Open tubular traps with an expanded inner diameter have very low
      pressure drop characteristics, which provides the possibility to construct new,
      simplified sampling systems.

PMID- 15481465
TI  - Detection of soil pollution by hydrocarbons using headspace-mass spectrometry and
      identification of compounds by headspace-fast gas chromatography-mass
      spectrometry.
AB  - The direct coupling of a headspace sampler with a mass spectrometer is proposed
      as a screening tool for the rapid detection of soil pollution by hydrocarbons
      from petroleum and derivatives. The samples are subjected to the headspace
      generation process, with no prior treatment, and the volatiles generated are
      introduced directly into the mass spectrometer, thereby obtaining a fingerprint
      of the sample analysed. Suitable treatment of the signal by chemometric
      techniques allows unequivocal characterisation of the different types of sample.
      The use of fast gas chromatography with a mass spectrometer detector coupled to
      the headspace sampler allows identification of the major hydrocarbons present in
      the mineral and organic polluted samples, interpretation of the results obtained,
      and demonstrates the analytical potential of headspace-mass spectrometry
      coupling.

PMID- 15481466
TI  - Trimethylsulfonium hydroxide as derivatization reagent for the chemical
      investigation of drying oils in works of art by gas chromatography.
AB  - A procedure for the determination of fatty acids (FA) and glycerol in oils has
      been developed. The method includes a derivatization step of the FAs into their
      methyl esters or a transesterification of the triacylglycerols with
      trimethylsulfonium hydroxide (TMSH), respectively. The analysis is carried out by
      gas chromatography with parallel flame ionization and mass spectrometric
      detection. The parameters involved in the transesterification reaction were
      optimized. Only the stoichiometric ratio of TMSH:total FA amount showed a
      significant influence on the reaction yield. Relative standard deviations for 10
      replicates were below 3% for all FAs studied and their linearity range was 0.5-50
      mmol/L, when using heptadecanoic acid as an internal standard. The final
      procedure was rapid and required little sample handling. It was then tested on
      fresh oil samples and presented satisfying results, in agreement with previous
      works.

PMID- 15481467
TI  - Evaluation of the analyses of tert-butyldimethylsilyl derivatives of naphthenic
      acids by gas chromatography-electron impact mass spectrometry.
AB  - Naphthenic acids are a complex mixture of carboxylic acids with the general
      formula CnH(2n+Z)O2 and they are natural, toxic components of crude oils. GC-MS
      analyses of tert-butyldimethylsilyl esters of naphthenic acids are used to
      estimate component distribution within naphthenic acids mixtures. Our evaluations
      of the GC-MS method showed that ions from column bleed erroneously appear as C14
      Z = -4 acids and that correcting for heavy isotopes of C and Si do not
      significantly affect ion distribution plots. Overall, the GC-MS method appears to
      overestimate the relative proportion of low-molecular-mass acids.

PMID- 15481468
TI  - Comparative study of analytical methods involving gas chromatography-mass
      spectrometry after derivatization and gas chromatography-tandem mass spectrometry
      for the determination of selected endocrine disrupting compounds in wastewaters.
AB  - Two GC-MS methods, based on the application of N,O
      bis(trimethylsilyl)trifluoroacetamide-derivatization-GC-MS (selected-ion
      monitoring) and GC-MS-MS without derivatization, respectively, were optimised and
      applied to the determination of a group of five selected endocrine disrupting
      compounds (EDCs) in wastewaters. Both methods included solid-phase extraction
      with Oasis HLB cartridges allowing an enrichment factor for wastewater samples of
      100-fold. The investigated EDCs were estrone, 17beta-estradiol, 17alpha
      ethynylestradiol, 4-tert-octylphenol and bisphenol A. Results obtained from the
      validation studies yielded comparable results in both cases. Recoveries in spiked
      wastewaters at 50 ng/l were higher than 90% for all the compounds, except for 4
      tert-octylphenol (75%). Repeatability and reproducibility were adequate, varying
      from 1.6 to 14%, except for estrone which reproducibility was 28% when the
      derivatization-GC-MS method was applied. Limits of detection calculated ranged
      from 2.5 to 27.5 ng/l with differences between both methods from 1.1 (estrone) to
      10.4 (bisphenol A) times. Both methods were successfully applied to the analysis
      of the target compounds in sewage treatment plant influents and effluents. Traces
      of bisphenol A, 4-tert-octylphenol, estrone and 17beta-estradiol were detected at
      concentration levels ranging from 13.3 to 1105.2 ng/l.

PMID- 15481469
TI  - Rapid and sensitive method for determining free amino acids in honey by gas
      chromatography with flame ionization or mass spectrometric detection.
AB  - This paper describes a rapid, sensitive and specific method for determination of
      free amino acids in honey involving a new reaction of derivatization and gas
      chromatography (GC) with flame ionization (FID) and mass spectrometric (MS)
      detection. The method allows the determination of 22 free amino acids in honey
      samples in a short time: 8 and 5 min for GC-FID and GC-MS, respectively.
      Quantitation was performed using Norvaline as internal standard, with detection
      limits ranging between 0.112 and 1.795 mg/L by GC-FID and between 0.001 and 0.291
      mg/L by GC-MS in the selected-ion monitoring mode. The method was validated and
      applied to a set of 74 honey samples belonging to four different botanical
      origins: eucaliptus, rosemary, orange and heather. The statistical treatment of
      data shows a correct classification of different origins over 90%.

PMID- 15481470
TI  - Development of pressurized liquid extraction and cleanup procedures for
      determination of organochlorine pesticides in soils.
AB  - The scope of this work is the development of a rapid, reliable and sensitive
      method for the analysis of organochlorine pesticides from soils by pressurized
      liquid extraction (PLE). The effect of four parameters (temperature, pressure,
      static time and cell volume) on the extraction efficiency was studied. The great
      extracting power of the PLE causes the extraction of numerous interfering
      substances, so a more efficient purification of this extract was necessary. In
      this work several sorbents have also been assayed to carry out the purification
      of soil samples: Florisil, silica, alumina, carbon, as well as combinations of
      them. Finally, the proposed analytical method was validated using a certified
      reference soil material (CRM804-050) and the results were compared with those
      obtained by other extraction techniques (Soxhlet and microwave-assisted
      extraction).

PMID- 15481471
TI  - Chlorotrimethylsilane, a reagent for the direct quantitative analysis of fats and
      oils present in vegetable and meat samples.
AB  - Acylglycerides present in oil seeds and meat can be transformed into volatile
      fatty esters using chlorotrimethylsilane (CTMS) and 1-pentanol as reagents. The
      volatile esters can then be analysed by GC. The method is quantitative and
      involves only minor sample manipulation. It often permits major recoveries of the
      total saponifiable lipids present in solid samples. A 40 min reaction time is
      enough to ensure the total conversion of saponifiable lipids to the corresponding
      FAPEs.

PMID- 15481472
TI  - Theories of human violence: implications for health care safety.
AB  - Violence is a complex, multifactorial entity with no single source of
      explanation. Although much research is underway into the nature and causes of
      violence, much of this research is done in isolation and published in highly
      specialized journals. Thus, there has been no journal review article for the
      administrator, clinician, or safety officer in health care settings who must
      address issues of safety on a daily basis. This paper provides that review by
      examining major cultural, biological, sociological, and psychological theories of
      violence. The review includes risk management strategies for, and the role of,
      health care facilities as societal institutions to curb violence. Many of the
      risk management strategies noted for health care settings may also be fielded in
      schools, courts, businesses, and other settings in which emergency services
      personnel are asked to respond.

PMID- 15481473
TI  - Child sexual abuse evaluations in an emergency room: an overview and suggestions
      for a multidisciplinary approach.
AB  - The physical and emotional distress associated with child sexual abuse may be
      compounded when the professional response in the emergency room (ER) to this
      critical incident is not well planned, comprehensive, and multidisciplinary. The
      purpose of this article is to provide an overview of the literature on emergency
      room (ER) evaluations of child sexual abuse and to provide recommendations for a
      multidisciplinary team approach to conducting these evaluations that includes
      physicians, nurses, mental health workers, and law enforcement officers.

PMID- 15481474
TI  - Assessment of PTSD symptoms in emergency room, intensive care unit, and general
      floor nurses.
AB  - A total of 125 registered nurses participated in an investigation of
      Posttraumatic Stress Disorder (PTSD) related symptoms and various levels of
      nursing care. The sample included 43 emergency room nurses (ER), 51 intensive
      care unit nurses (ICU), and 31 general floor nurses (GF). All participants were
      assessed on measures of PTSD, social support, dissociation, anxiety, depression,
      and demographics. Contrary to expectations, the ER nurses were not found to be
      uniquely stressed by their work when compared to the other nursing groups.
      Results indicated that all nurses experienced a significant level of anxiety but
      were not in the clinically significant range for PTSD, depression, or
      dissociation. It was inferred that social support played a significant role in
      helping nurses cope with work-related stress. Nevertheless, the high anxiety
      levels of all nurses were highlighted as a concern. It was suggested that
      exposure to numerous traumatic experiences over a lifetime of nursing, and a lack
      of control over these experiences, contributed to the high anxiety levels seen in
      all nursing groups.

PMID- 15481475
TI  - Comprehensive psychosocial emergency management promotes recovery.
AB  - Recently published conclusions erroneously criticize early psychological
      interventions, and more specifically target critical incident stress debriefing
      (CISD), as ineffectual responses to human needs following emergencies. The
      assertions may influence some practitioners to reconsider current commitments to
      providing early crisis support, or other aspects of early psychological
      interventions, in the first hours and days after an emergency occurs. The
      arguments used are misleading in that they confuse the distinctions between CISD
      and other components of early psychological interventions, and seek to impugn the
      efficacy of CISD with research findings that have methodological flaws and
      limited generalizability. Theoretically sound approaches to the phenomenology of
      earliest reactions and early psychological interventions must build upon survivor
      and community needs in the aftermath of trauma, and upon an understanding of the
      psychobiological, evolutionarily-determined aspects of traumatic stress within
      attachment schema. It is now possible to postulate a broader approach to the
      early psychosocial needs of persons affected by trauma, whether they are
      survivors, rescuers, or witnesses. Comprehensive Psychosocial Emergency
      Management utilizes systematic study of the risk and protective factors within
      the phenomenology of traumatic stress that disrupt processes which otherwise
      result in dysfunction. Early psychological intervention enhances coping and
      resilience, and promotes recovery for all.

PMID- 15481476
TI  - Training-as-treatment: effectiveness of the Certified Compassion Fatigue
      Specialist Training.
AB  - Mental health and other service professionals who work with trauma survivors
      often experience the debilitating effects of compassion fatigue and caregiver
      stress. Leaders within the field have called for effective, empirically supported
      interventions for professionals who experience these negative effects. In
      response to the call, this study examines the treatment effectiveness of the
      Certified Compassion Fatigue Specialist Training (CCFST) for 83 participating
      mental health professionals. Results show a statistically and clinically
      significant decrease in participants' compassion fatigue and burnout symptoms and
      increase in their compassion satisfaction. A "training-as-treatment" effect of
      CCFST is introduced, described, and evaluated. Discussion of these findings,
      clinical implications, limitations, and future directions are provided. CCFST
      appears to be an effective intervention for ameliorating compassion fatigue
      symptoms in mental health professionals.

PMID- 15481477
TI  - Poetry, trauma, and the spirit.

PMID- 15481478
TI  - Journalists and trauma: a brief overview.
AB  - In the past decade, journalism experts realized what those in the fields of
      emergency response and management have known for much longer: That journalists
      could be psychologically affected by the traumatic events they covered. Although
      a fledging field of study, groups such as the Dart Center for Journalism and
      Trauma, based at the University of Washington, in Seattle, WA, have dedicated
      themselves to advocating the ethical and thorough reporting of trauma, educating
      working journalists about trauma and serving as a forum for journalists to
      discuss topics related to covering traumatic events. The three major studies
      conducted on the subject--focusing on print journalists, photojournalists, and
      war journalists--have discovered that journalists can suffer sleeplessness,
      flashbacks, and in most extreme cases, posttraumatic stress disorder. According
      to Dr. Roger Simpson, director of the Dart Center, there is much work still to be
      done on the subject.

PMID- 15481479
TI  - Newborn outcome after assisted reproductive technology: experiences and
      reflections from Poland.
AB  - In spite of much ethical uncertainty and wide variations in obstetric and
      neonatal outcomes reported in the literature, we have studied the outcome of
      Polish newborns after assisted reproductive technology (ART). In all of our
      patients, both obstetrics and neonatal care were performed in the Level Three
      Center in Poznan, Poland. A total of 45 and 82 newborns were analyzed from the
      ART and the control group, respectively. We analyzed gestational age, birth
      weight, Apgar score, duration of hospitalization, newborn mortality, and
      congenital malformations. We found a far higher rate of mothers over 35 years and
      with university education in ART compared to controls. The incidence of cesarean
      section and birth weight <1,500 g was much higher in ART. Newborn mortality was
      much higher among ART newborns compared to controls and was related to premature
      delivery of triplet pregnancy. The most important factor resulting in high
      neonatal mortality in our study group was multiple pregnancy. We consider the
      lack of regulation in Poland concerning the number of replaced embryos as a main
      factor influencing newborns' outcome after ART.

PMID- 15481480
TI  - Neural mechanisms of pain.
AB  - Pain is one of the most common reasons that patients seek medical care, and
      affects one-third of the population within a given year. Pain is not always
      "functional" (physiologic), but often is pathologic, or chronic. This article
      describes the mechanisms of pain, showing how a protective response can become
      altered to chronic pain state, such as chronic pelvic pain.

PMID- 15481481
TI  - Intimate partner violence and birth outcomes: a systematic review.
AB  - OBJECTIVE: There is a lack of comprehensive information on the relationship
      between domestic physical and emotional violence and pregnancy outcomes.
      Accordingly, we undertook this systematic review of the literature to examine the
      evidence on the association between physical and emotional abuse and pregnancy
      outcomes. STUDY DESIGN AND METHOD: A comprehensive literature search was carried
      out using pertinent key words that would retrieve any research article pertaining
      to the topic. This was supplemented by cross-referencing of the articles. A total
      of 296 articles were found; case reports and articles that failed to satisfy the
      study inclusion criteria were removed and 30 articles were included in the
      review. RESULTS: Overall, adverse pregnancy outcomes, including low birth weight,
      maternal mortality and infant mortality are significantly more likely among
      abused than nonabused mothers. Abused pregnant mothers present more often than
      nonabused mothers with kidney infections, gain less weight during pregnancy, and
      are more likely to undergo operative delivery. Fetal morbidity, such as low birth
      weight, preterm delivery, and small size for gestational age are more frequent
      among abused than nonabused gravidas. The risk for maternal mortality is three
      times as high for abused mothers. Black abused mothers are 3-4 times as likely to
      die as their white counterparts. Unmarried victims are also three times as likely
      to die as married abused mothers. Intimate partner violence is also responsible
      for increased fetal deaths in affected pregnancies (about 16.0 per 1000).
      CONCLUSION: Intimate partner violence is often a life-threatening event to both
      the mother and the fetus. This, in addition to the heightened level of feto
      maternal morbidity and mortality, represents clear-cut justification for routine
      systematic screening for the presence of abuse during pregnancy.

PMID- 15481482
TI  - Laparoscopic Filshie clip sterilization and selective use of the methylene blue
      dye test.
AB  - In laparoscopic Filshie clip sterilization, difficulties may arise in identifying
      the length of the fallopian tube, with the possibility of failure of
      sterilization. This article describes a novel intraoperative method of
      demonstrating adequate tubal closure.

PMID- 15481483
TI  - Tuberculosis among foreign-born children in the State of Florida, 1993--1999: a
      re-emergence phase after a sustained decline?
AB  - STUDY OBJECTIVE: To determine the temporal trend of tuberculosis disease among
      foreign-born children in the State of Florida. DESIGN AND SETTING: Descriptive
      population-based study on data obtained from the Tuberculosis Control and
      Surveillance Program in the State of Florida. We employed Poisson assumption to
      derive estimates for rates of tuberculosis among US-born and foreign-born
      children in the studied population. We also applied linear and nonlinear
      regression equations to describe the best trajectories for observed temporal
      trends in incidence cases of the disease. PATIENTS: All cases of tuberculosis
      disease among children notified in the State of Florida between 1993 and 1999
      inclusive. MAIN RESULTS: The incidence rate of TB over the study period was five
      times higher among foreign-born children (11.3 per 105; CI = 8.0-14.6 per 105) as
      compared to US-born (1.7 per 105; CI = 0.8-4.2 per 105). Whereas, new cases of TB
      among US-born children have continuously and significantly dropped throughout the
      period of study, our data indicated that the decline achieved from 1993 to 1996
      among foreign-born children has ceased, and a resurgence of tuberculosis in this
      population was apparent. CONCLUSIONS: Our data tend to suggest a re-emergence of
      tuberculosis among foreign-born children in the State of Florida as from 1997
      after several years of decline. There is a need for a more in-depth investigation
      to elucidate and address causes responsible for the resurgence if the current
      battle to eliminate tuberculosis from the State is to succeed.

PMID- 15481485
TI  - Commentary: Polycystic ovarian disease (PCOD): a misnomer, looking for a new
      name.
AB  - This commentary highlights controversies associated with the nomenclature of
      polycystic ovarian disease (PCOD). It also deals with the authors' suggestion for
      the new name of polyfollicular ovarian disease (PFOD).

PMID- 15481487
TI  - Palliative care: innovation in care at the end of life.

PMID- 15481486
TI  - African American elders' perceptions of the influenza vaccine in Durham, North
      Carolina.
AB  - OBJECTIVE: To qualitatively explore community perceptions among elderly African
      Americans about what makes it easy or difficult to get vaccinated for influenza.
      SAMPLE: A total of 28 elderly (age 65 years or older) African Americans living in
      Durham County, North Carolina, participated in this study. DATA COLLECTION
      METHODS: In-person, open-ended interviews were conducted to perform a content
      analysis on factors influencing influenza vaccination use, or lack thereof in an
      elderly African American population. Interviews were conducted in
      participants'homes and at senior centers in Durham County, North Carolina.
      Interviews were transcribed and analyzed to identify themes. PRINCIPAL FINDINGS:
      Ten facilitators to encourage obtaining vaccinations were identified, including
      reminders from a doctor to get the influenza vaccination and the perception that
      the vaccination prevents influenza. Eight barriers were identified, including
      community perceptions to not get vaccinated and the fear of getting the 'flu" fom
      the vaccination itself. CONCLUSION/RELEVANCE: The study identified community
      perceptions of what makes it easy or difficult for elderly African Americans to
      get vaccinated for influenza. The findings will be useful to design and implement
      programs targeted to improving vaccination rates in health clinics or private
      physicians offices since the elderly are more likely to receive influenza
      vaccinations in primary care settings.

PMID- 15481488
TI  - Hospice: a vital service facing increasing demands.

PMID- 15481489
TI  - Palliative care: more than just care from a friendly relative.

PMID- 15481490
TI  - Hospital-based palliative care units: answering a growing need.

PMID- 15481491
TI  - A brief review of North Carolina's law on dying.

PMID- 15481492
TI  - Spiritual care at the end of life: what is it and who does it?

PMID- 15481493
TI  - Opioids in end-of-life care: promises and problems.

PMID- 15481494
TI  - Promoting pain relief and preventing abuse of pain medications: a critical
      balancing act.

PMID- 15481495
TI  - Addressing pain management and palliative care: the official position of the
      North Carolina Medical Board.

PMID- 15481496
TI  - Guiding the decisions of physicians and families in end-of-life care: the case of
      long-term feeding tube placement.

PMID- 15481497
TI  - Current end-of-life issues: a practicing physician's view.

PMID- 15481498
TI  - Why the Patient Self-Determination Act has failed.

PMID- 15481499
TI  - Deaths among North Carolinians age 85 and older.

PMID- 15481500
TI  - Infant mortality in North Carolina.

PMID- 15481501
TI  - Demand for CME programs on cancer care among primary care physicians in North
      Carolina.

PMID- 15481502
TI  - Making babies. It's an expensive gamble, but childless couples are trying
      reproductive therapy in record numbers.

PMID- 15481503
TI  - Recommendation 20 from the National Review of Nursing Education: to build faculty
      practice into the workload and performance expectations of nurse academics.

PMID- 15481505
TI  - Re-thinking approaches to undergraduate health professional education:
      Interdisciplinary Rural Placement Program.
AB  - The Interdisciplinary Rural Placement Program involved the development,
      implementation and evaluation of a common rural primary health care module.
      Designed for undergraduate nursing, medical and pharmacy students of the
      University of Tasmania, students undertook clinical experiences and a
      collaborative primary health care project at two different Rural Health Teaching
      Sites across Tasmania. The aim of the project was for interdisciplinary students
      to work and learn together to enhance their understanding of the cooperative and
      collaborative nature of professional practice among rural health care workers.
      This paper will describe the development and implementation of the
      Interdisciplinary Rural Placement Program and critically discuss the outcomes in
      relation to nursing. In this paper, three issues will be explored. Firstly, how
      student nurses questioned their sense of subordination when in fact the level of
      recognition by their interdisciplinary peers led them to refute this. Secondly,
      concerns with overcoming the difficulties of coordinating student recruitment and
      conflicting timetables, while working within existing curricula, will be
      discussed. The final issue explores the student nurses' recognition that despite
      inherent tensions and conflict, the need to work as a cohesive and cooperative
      interdisciplinary team was vital. This project highlighted the challenges that
      health professions continue to work through in contemporary practice and
      education sectors. A key recommendation for education providers is that true
      interdisciplinary education must be achieved through an experiential framework.

PMID- 15481504
TI  - Nurse manager turnover in New South Wales during the 1990s.
AB  - The principal aim of the research reported in this paper was to explore the
      nature and incidence of various environmental, personal, and work-related factors
      that are implicated in turnover and retention amongst nurse managers. The study
      sought to ascertain whether or not turnover patterns during the 1990s were
      similar for nurse managers working in different specialist areas and settings of
      health services within New South Wales, and to discover the main reasons why
      nurse managers change their jobs or stay in their jobs. This paper reports the
      main findings, and highlights how the factors implicated in nurse manager
      turnover and retention, whilst not significantly dissimilar across different
      cohorts of nurse managers, do not parallel those that are implicated in turnover
      amongst nurses generally. The research has found that the main reason nurse
      managers change their jobs is for career development, often within the same
      organisation or, otherwise, the same health sector or geographic area. Second to
      this is leaving due to dissatisfying aspects of the job and/or work environment.
      Some differences have been observed in the propensity to change jobs and in the
      relative importance of particular influences on job changes in certain practice
      areas and health sectors. Seven per cent of nurse managers would like to quit
      their present jobs. However, almost 70% are happy to stay either because the job
      suits their skills and qualifications, the job is personally
      satisfying/rewarding, they enjoy the company of their coworkers, or their hours
      of work suit their needs.

PMID- 15481506
TI  - Exploring nursing: once a nurse, never a woman".
AB  - In August 2002, Laura Rohricht celebrated her fiftieth year of nursing in
      Brisbane. Hers has been a remarkable career, characterised by adversity,
      opposition and the disciplinary nature of nursing training in the 1950s. The
      strength of character she displayed in her youth would have been defined by many,
      especially by her father, as inappropriate for a girl. Yet it was this strength
      that played a critical role in enabling her to establish and maintain her career.
      This biographical profile of Laura Rohricht draws on interviews with Laura
      herself and conversations with several of her colleagues and friends.

PMID- 15481507
TI  - Contemporary enrolled nursing practice: opportunities and issues.
AB  - Over the last decade, Australia, as with the rest of the developed world, has
      experienced a widespread labour market decline in the numbers of nurses in the
      health workforce. Concurrent with this nursing shortage, the second level nurse
      has, in many countries, ceased to be recognised as a legitimate nursing role. In
      Australia, recent research indicates that the enrolled nurse role, though
      contentious, is consolidating as a core component of the health care workforce.
      This paper reports on national research that examined the role and function of
      the enrolled nurse in Australia and reviewed the Australian Nursing Council Inc
      (ANCI) National Competency Standards for Enrolled Nurses. Specific issues related
      to the contemporary role and function of enrolled nurses, namely supervision,
      scope of practice and education, are also discussed.

PMID- 15481508
TI  - Royal Rehabilitation Centre Sydney: towards Clinical Development Units (Nursing).
AB  - Clinical Development Units (Nursing), also known as Practice Development Units
      and Nursing Development Units, are nursing units that continually strive for
      excellence in nursing practice. Nursing units endeavouring to attain, or having
      achieved, the standards required of a Clinical Development Unit (Nursing)--CDU(N)
      -provide a very motivating and stimulating environment for nursing professional
      development. This paper provides readers with an understanding of the
      underpinnings of a CDU(N) along with why and how a nursing unit would strive for
      this status. A priority of senior nurse management at a rehabilitation facility
      in Sydney, the Royal Rehabilitation Centre, has been working towards the
      upgrading of every nursing unit in their facility to the level of a CDU(N) over
      the past three years. By way of an innovative course, the Clinical Development
      and Leadership course developed by Professor Jennifer Greenwood in 1997, senior
      nurses are being provided with the knowledge and skills to enable them to work
      towards their goal of becoming part of a Clinical Development Unit (Nursing).

PMID- 15481510
TI  - CPD: using evidence based clinical practice guidelines in the management of
      anaemia in patients with chronic renal failure.

PMID- 15481509
TI  - Women-centred care and caseload models of midwifery.
AB  - OBJECTIVE: A partnership caseload model of midwifery-led practice was developed
      and introduced as an option of maternity care for low risk women at our local
      health service. To assess the benefits of this new practice model, aspects of
      continuity, choice, control and satisfaction were examined in women receiving
      Primary Health Midwifery Care (PHMC) and standard hospital care (SHC). DESIGN AND
      SETTING: A descriptive comparative design was used and survey data were collected
      using a modified version of the Mason Survey of Womens' Experience of Maternity
      Care from a convenience sample of women receiving PHMC (n = 357) and SHC (n =
      202) from a large metropolitan health service. FINDINGS: Overall, more women
      receiving PHMC experienced key aspects of women-centered care-choice, control and
      continuity than women receiving SHC. KEY CONCLUSIONS: This study, within the
      limitations of its design and sample size, confirms that low risk women have
      positively responded to partnership caseload midwifery practice, and the practice
      model has supported women-centred care with special benefits for primipara women.

PMID- 15481511
TI  - What can research do for you?

PMID- 15481512
TI  - Early discharge following uncomplicated appendicectomy in children.
AB  - This cohort evaluation investigated the discharge of 15 children within 12 to 24
      hours following an uncomplicated appendicectomy who were subsequently supported
      by an outreach nurse. By monitoring the child's progress, providing the support
      the family was expected to require and offering professional back-up for any
      unforeseen problems the outreach nurse ensured the child's safety and improved
      quality of care after early discharge from the hospital. The pivotal importance
      of the outreach nursing input was demonstrated when the expected visit did not
      materialise for one child.

PMID- 15481513
TI  - Home from home: evaluation of a respite service in Kent.

PMID- 15481514
TI  - Improving inter-hospital transfer.

PMID- 15481515
TI  - Complementary therapies for children: aromatherapy.

PMID- 15481516
TI  - Sexual health and chronic illness in childhood.

PMID- 15481517
TI  - Assessment and management of the child requiring chronic haemodialysis.
AB  - A child with acute or end stage renal failure requiring haemodialysis has
      specific needs. This article provides the opportunity for nurses to update their
      knowledge and understanding of the care needs and psychosocial impact of
      haemodialysis on the child and family.

PMID- 15481518
TI  - Will dental insurance affect the quality of dental care?

PMID- 15481519
TI  - Unconscious patients and the supine position.

PMID- 15481520
TI  - The Dental Council and complaints against dentists.

PMID- 15481521
TI  - The Ceka Project--Irish volunteer dentistry in Kenya.

PMID- 15481522
TI  - Protecting your income.

PMID- 15481523
TI  - Practical crown and bridge for predictable aesthetics.

PMID- 15481524
TI  - Overview of TMD and orofacial pain.

PMID- 15481525
TI  - Statistical and clinical significance: alternative methods for understanding the
      importance of research findings.
AB  - Statistical significance is an important tool for interpreting a study's results,
      but statistical significance provides an incomplete picture of results. The
      likelihood of obtaining statistically significant results can be manipulated by a
      researcher who uses large sample sizes or who compares treatments that are
      expected to differ greatly in outcome. Measures of effect size provide an
      additional tool for understanding the results of a study and evaluating the
      importance of the results. Meta-analyses and estimates of clinical significance
      can also help clinicians properly evaluate research findings.

PMID- 15481526
TI  - Intraosseous mandibular lipoma (IML): a case report and review of the literature.
AB  - Intraosseous mandibular lipoma (IML) is a rare benign tumour and is infrequently
      associated with unerupted teeth. This report describes an IML associated with an
      unerupted impacted mandibular wisdom tooth.

PMID- 15481527
TI  - [Food safety : an important public health problem in China].

PMID- 15481528
TI  - [Functional study on TGF-beta/Smads signaling pathway in human ovarian cancer
      cells].
AB  - Resistance to the growth inhibitory effects of transforming growth factor-beta
      (TGF-beta) is a characteristic of many transformed cells. The purpose of this
      study was to determine the response of ovarian cancer cells to TGF-beta1 and to
      investigate the roles of components of the TGF-beta/Smads signaling pathway in
      carcinogenesis of ovarian cancer. Three ovarian cancer cell lines, HO-8910, HO
      8910PM and SKOV3, were treated with TGF-beta1 and assayed for growth response by
      MTT assay. Furthermore, expression and subcellular localization of the components
      of TGF-beta/Smads signaling pathway in these cell lines in the absence or
      presence of TGF-beta1 were determined by RT-PCR and immunofluorescence analysis.
      We found that proliferation of SKOV3 cell was not significantly inhibited by TGF
      beta1 while it expressed all components of the TGF-beta/Smads signaling pathway.
      After exposure to TGF-beta1, Smad7 protein in SKOV3 increased transiently and
      translocated to cytoplasm from nucleus while P-Smad2 translocated into nucleus
      from cytoplasm. Taken together, the results suggested that the TGF-beta/Smads
      signaling pathway remained functional in human ovarian cancer cells, HO-8910, HO
      8910PM and SKOV3, and the abnormalities of the downstream effectors of Smads
      proteins might contribute to the resistance of SKOV3 cell to TGF-beta1.

PMID- 15481529
TI  - [Effect of the regulation of IGFs system components in retinoic acid-induced
      congenital clubfoot].
AB  - The fetal rat models with congenital clubfoot were constructed by treating 24
      Wistar rats with all trans retinoic acid (ATRA). The MC-3T3-E1 cells were
      cultured with ATRA, 17 beta-estrogen (E2) or combinations of the two chemicals.
      The flow cytometer was used to determine the cell proliferation. The insulin-like
      growth factor-II (IGF-II ) and IGF conjugated protein-6 (IGFBP-6) mRNA level in
      rat calvaria bone tissue and MC-3T3-E1 cells were detected by northern blotting
      analysis and reverse transcription polymerase chain reaction. The congenital
      clubfoot of fetal rat was induced by ATRA in concentration of 100 approximately
      140 mg/kg with dosage-dependence effect. The expression of IGF-II mRNA and cell
      proliferation were enhanced by E2(1 x 10(-6) mol/L) in rat calvaria bone tissue
      and MC-3T3-E1 cells, whereas the IGFBP-6 mRNA was increased. ATRA(1 x 10(-6)
      mol/L), however, inhibited the effect of E2 on regulation of IGF- II gene and
      IGFBP-6 gene as well as MC-3T3-E1 cell proliferation. These findings provide the
      evidence that ATRA can induce congenital skeleton malformation and congenital
      clubfoot in pregnant Wistar rats. IGF-II and IGFBP-6 are important regulative
      factors for skeleton development and osteoblast proliferation in rat.

PMID- 15481530
TI  - Isolation and chromosomal localization of ZFX homologue in genome of rice field
      eel (Monopterus albus Zuiew).
AB  - When used as a probe in rice field eel (Monopterus albus Zuiew) genomic Southern
      blotting hybridization, the giant panda Zfx gene hybridized strongly to a
      fragment of about 9.5 kb. A 512 bp long DNA fragment has been isolated by
      polymerase chain reaction from rice field eel genomic DNA using the primers for
      amplifying zinc finger repeats 7 to 13 of mammalian and reptilian ZFX-related
      genes. Cloned in pBS, four recombinant plasmids were selected randomly from male
      and female specimens and sequenced. The nucleotide sequences in these clones were
      identical and showed 88% and 87% identity to human ZFX and ZFY respectively. But
      its extent of homology was greater with American alligator Zfc (90%). And the
      amino acid sequences of the putative protein showed 95.9%, 95.9% and 93.5%
      identity to human ZFX and ZFY and American alligator Zfc respectively. Thus, the
      cloned sequence encodes a homologue of mammalian ZFX/ZFY and was named Zfa for
      rice field eel zinc finger domain gene. It appears that the mammalian and
      reptilian ZFX-related genes evolved from fish ancestors with a considerable
      degree of conservation. By fluorescence in situ hybridization, the Zfa has been
      mapped to rice field eel chromosome 1 and at the position of 60.1 +/- 0.38 from
      the centromere. Chromosomal mapping of fish genes related to mammalian X-linked
      genes might lead to further understanding of the evolution of vertebrate sex
      chromosomes.

PMID- 15481531
TI  - [Karyotypic analysis from two clones of gynogenetic Pengze crucian carp
      (Carassius auratus of Pengze)].
AB  - Pengze crucian carp (Carassius auratus of pengze), one of the most popular
      cultural fishes in China, is an endemic bisexual population with natural
      gynogenetic reproduction mode. Just like Silver crucian carp, investigation on
      the karyotype of Pengze crucian carp is important to understanding the diversity
      and the evolution of the unisexual vertebrates. Two distinguishable gynogenetic
      clones of Pengze crucian carp, named clone H and clone L, respectively,were
      detected recently. In this study, the chromosomes number and karyotype of the two
      clones were analyzed using chromosomes of kidney cell-PHA culture in vivo
      prepared by flame-drying technique. The results show that the chromosome numbers
      and karyotypes of the two clones are different. Clone H has 156 chromosomes in
      its karyotype with 42 metacentric, 36 submetacentric, 39 subtelocentric, 33
      telocentric, and six supernumerary chromosomes; the karyotype of clone L contains
      162 chromosomes with 36 metacentric, 45 submetacentric, 33 subtelocentric, 36
      telocentric, and twelve supernumerary chromosomes. The karyotype formula of 150
      basic chromosomes of clone H is 3n = 42M +36SM +39ST +33T,NF = 228; and the
      karyotype formula of 150 basic chromosomes of clone L is 3n = 36M +45SM +33ST
      +36T, NF = 231. The discovery of the two different gynogenetic clones indicates
      that the genetic diversity also exists in the Pengze crucian carp, similar to
      that in the Silver crucian carp.

PMID- 15481532
TI  - [Construction of AFLP molecular markers linkage map and localization of green
      cocoon gene in silkworm (Bombyx mori)].
AB  - Based on an improved method of AFLP, AFLP markers were employed for construction
      of a linkage map and localization of Gc gene used a set of 44 backcross lines(
      BC1) of silkworm ( Bombyx mori) as a mapping population. In this work, all
      together 3 956 bands were obtained by 28 pairs of primers and 141.3 bands each
      primer pair on average. Among them 2 836 bands were in good agreement with the
      segregation pattern. A total of 1 018 (25.7%) polymorphic AFLP markers were
      detected. The 693 (68.1%) of polymorphic markers with 1:1 segregation ratio ( P <
      or = 0.05) were obtained. Furthermore,The analytical model was based on the
      backcross type and the parameters were set as following: LOD = 3.0, maximum
      recombination value of 0. 20 and use the command ' group', 'compare', 'try',
      'map' and 'ripple' to construct the linkage maps. 407 of the 693 loci were chi2
      tested in agreement with 1:1 segregation were divided into 33 linkages by
      Mapmaker/Exp(Version 3.0), with a total map distance of 3 676.7 cM and a mean
      distance of 9.1 cM between markers. The morphological gene Gc was located between
      L-P4T6-107 and L-PT6T4-84 on linkage group 22. In addition, 286 markers were not
      included in the linkage groups. The efficiency of loci mapping was 58.7%. Among
      the 33 linkage groups, the morphological marker Gc classically localized on
      linkage group 15 was relocated on linkage group 22 on the map, suggesting that
      this molecular linkage group corresponds to linkage group 15 on the linkage map
      based on morphological characters. All these have laid an important base for the
      marker assisted breeding of the silkworm.

PMID- 15481533
TI  - [Identification and characterization of alternativly splicing variants for murine
      mater gene].
AB  - Mater encoding an oocyte-specific autoantigen,and is associated with premature
      autoimmune ovarian dysgenesis (AOD) in mouse. Based on RT-PCR, cDNA cloning,
      screening, sequencing and analysis, we have detected a total of four Mater splice
      variants, designated as variant B, E, F and G. All these splicing forms are in
      frame in terms of expected protein products. Among these, B was consistent with
      the previous report, whereas E, F, G belong to novel splice variants that have
      not been reported previously. Variant E lacks exon 6, variant F both lacks exon
      10 and retains a part of intron 8, variant G lacks part of exon 14, and variant H
      lacks part of exon 13. The cDNA sequences at all the exon-intron boundaries
      confirms to the "GT-AG" splicing rule. Variant B, E, F exist in all the four
      strains. Variant G exists only in SWR/J. According to the cDNA sequences of these
      four splice variants, amimo acid sequences of the corresponding expected protein
      isoforms were deduced, and their potential functional effects were predicted in
      this thesis. Further identification and characterization of these expected
      protein isoforms would provide valuable information for their functional
      importance.

PMID- 15481534
TI  - Identification of QTLs for weight and cross-sectional area on cervical
      enlargement of spinal cord in mice.
AB  - Two inbred strains of mice, A/J, C57BL/6J and F2 intercross progenies,were used
      for QTL mapping for weight and cross-sectional area on cervical enlargement of
      spinal cord in mice. 13 QTLs located on Chromosome 2, 4, 8, 14, 15, 17, 18, 19
      and X, respectively, for these two traits were found. Six QTLs were responsible
      for the cord weight, four for the cross-sectional area and three for both. Among
      13 QTLs, three QTLs (P < 0.01) termed SC1 (located near D15Mit158) ,SC2
      (DXMit140) and SC3 (DXMit64) accounted for 24%, 19% and 15% of the total variance
      in weight phenotype, and -3.78, 3.41 and 2.06 mg additive effect, respectively.
      The P value of other QTLs is between 0.01 and 0.05. SC1 is only one QTL that
      responsible for both weight and cross-sectional area in three QTLs above. This
      study revealed the location of major QTLs related size of spinal cord in mice,
      and may be helpful in fine mapping and ultimate identification of candidate
      genes.

PMID- 15481535
TI  - [Sequencing analysis on partial translated region of uncoupling protein-3 gene
      and single nucleotide polymorphism associations with the porcine carcass and meat
      quality traits].
AB  - Porcine uncoupling protein-3 gene was used to study its effect on carcass and
      meat quality traits. The UCP3 partial translated regions in skeletal muscle from
      four pig breeds were sequenced and the comparison of the fragment sequences among
      four pig breeds showed that there were three coding-region single nucleotide
      polymorphisms (cSNP), of which the mutation at 842 bp of the open reading frame
      can result in the amino acid chang between methionine and threonine, so we
      selected the mutation as polymorphic site. The detection of polymorphic fragment
      by the technique of single strand conformation polymorphism (SSCP) and chi2
      analysis among three pig breeds indicated that the distribution of three
      genotypes(AA, AB and BB) was significantly different between Meishan and Large
      White or Meishan and Landrace( P < 0.01). In addition, association analysis of
      UCP3 polymorphism with carcass and meat quality traits was conducted in the F2
      generation from the Large White x Meishan resource family, the results with GLM
      analysis showed that UCP3 polymorphism has significant effect on several carcass
      and meat quality traits and also additive effect on some carcass and meat quality
      traits predominated in the resource family. It implied that UCP3 gene could be a
      candidate gene locus or a linked marker to a major gene, which affects the
      porcine carcass traits and meat quality traits significantly.

PMID- 15481536
TI  - [Studies on the infectivity by porcine endogenous retrovirus with porcine skin
      fibroblast in vitro and in vivo].
AB  - To understand the infectivity by porcine endogenous retrovirus with porcine skin
      fibroblast cell in vitro and in vivo, porcine skin fibroblast cell established by
      our laboratory were co-cultured with neo/HEK293 cell for the infection of PERV in
      vitro, and were subcutaneously transplantated to SCID (severe combined immuno
      deficiency) mice for the infection of PERV in vivo, laying the foundation for
      valuation of biologic safety of xenotransplantation. The event of neo/HEK293
      cells infected by PERV occurred during co-culture of porcine skin fibroblast
      cells with neo/HEK293 cells, expanding the rang of the infection of porcine
      endogenous retrovirus. After pig cells transplantated subcutaneously in SCID
      mice, the microchimerism (78.57%) of pig cells occurred widely, and there was
      phenomena of integration of PERV provirus (85.71%) in several organs or tissues
      remote from the injected sites, indicating infection of PERV in SCID mice in
      vivo, yet, there is no evidence of active viral replication in analysis of PERV
      env RNA of these tissues or organs. The infectivity of porcine endogenous
      retrovirus with porcine skin fibroblast cells in vitro and in vivo were
      demonstrated in this study, and there is no evidence of active viral replication
      of PERV in vivo. It is an important event of biologic safety which attention must
      be paid to potential hazard of infectious interspecies transmission of PERV
      during xenotransplantation.

PMID- 15481537
TI  - [QTL mapping for ear shape based on a commercial pig population].
AB  - A commercial pig population, including 19 hybrid boars [Pietrain x (Pietrain x
      Hampshire), 52 hybrid sows [Leicoma x (Large White x Landrace)] and their 332
      offspring, was used to construct a reference pedigree, with which a linkage map
      of whole genome was created using 172 microsatellite markers and three type-1
      markers (RYR1, PRKAG3, PIT1). The average of the notes of ear shape (pricky ear
      shape noted by 1; middle ear shape noted by 0; floppy ear noted by -1) detected
      by a trained technician is 0.23 and the variation 0.82. QTL mapping for ear shape
      was carried out with the least square regression method. The result showed that
      only one QTL for ear shape was detected at 1% genomewise level at the end
      (between Sw1881 and Sw322) of the chromosome 6 and no QTL was found on the other
      chromosomes even at 10% chromosome-wise level.

PMID- 15481538
TI  - [Identification and analysis of a group of highly conserved trs-like genes in
      rice].
AB  - There are at least ten transcriptional trs-like genes in rice that have been
      confirmed by RT - PCR and sequencing, based on the annotation results of rice
      genome and homologous search. These ten genes correspond to six of the ten known
      subunits of TRAPP complex in yeast. Four pairs of them are duplicates while the
      other two are unique according to the known rice genomic sequences. All of the
      ten genes are constitutively expressed in rice tissues and share phylogenetic
      homology to some extent with other eukaryotic trs-like genes in their gene
      structures and protein sequences.

PMID- 15481539
TI  - [Analysis on the inheritance of inhibition and anti-inhibition of coleoptile
      purple line in rice and the SSR location of Ai(t) gene].
AB  - The ratio of purple line: no-purple line(13:3) was observed in six different F2
      populations produced by crossing between parents with purple line and no-purple
      line in coleoptile. The backcross of XNA//XNA/ 21A150 (XNA, no-purple line and
      CMS, as the recurrent parent) resulted in a ratio of 1:1 (purple line: no-purple
      line). Genetic analysis showed that the expression of rice coleoptile purple line
      was influenced by two genes, inhibiting gene I and anti-inhibiting gene Ai(t). I
      gene inhibits P gene of C_A_P_ system and Ai(t) inhibits / gene, respectively.
      The gene pools of Ai(t) ai(t) and ai(t) ai(t) were constructed with BF1 of
      XNA//XNA/21A150. SSR analysis indicated that Ai(t) gene was linked with the
      markers of RM335, RM295, RM287 and RM21 and the genetic distance from Ai(t) to
      these four markers were 2.8 cM, 10.2 cM, 13.9 cM, 26.1 cM, respectively.

PMID- 15481540
TI  - [Pyramiding of senescence-inhibition IPT gene and Xa23 for resistance to
      bacterial blight in rice (Oryza sativa L.)].
AB  - Transgenic lines (GC-1) carrying a senescence-inhibition cheimeric gene, IPT
      (isopentenyl transferase) gene, CBB23, a isogenic lines carrying Xa23 gene for
      resistance to bacterial blight, and Hexi15, a commercial cultivar showing high
      resistance to blast disease, were used as donors to pyramid IPT gene and Xa23 by
      marker-assisted selection (MAS). Seventeen BC1F1 plants pyramiding Xa23 gene and
      IPT genes were obtained from three multi-cross combinations. Then, the plants
      carrying Xa23 and IPT genes were crossed with parental lines of two-line hybrid
      rice, such as 9311, E32, Pei' ai 64S and W9834S. The progenies were backcrossed
      the acceptor parents. A total of 17 plants carrying Xa23 and IPT genes were
      detected by PCR, disease resistance identification and analysis of CTK contents
      of in the four combinations of "(9311///Hexi15/CBB23// GC-1) x 9311",
      "(E32///Hexi15/CBB23//GC-1) x E32", "(Pei'ai 64S///Hexi15/CBB23//GC-1) x Pei' ai
      64S" and "(GC-1/CBB23//W9834S/Hexi15) x W9834S". These plants showed resistance
      to blast disease by inoculating test using 21 the lines of Pyricularia grisea
      from Northern China. Six plants of BC2F1 pyramiding Xa23 and IPT genes were
      further obtained in the combinations of "[(9311///Hexi15/CBB23//GC-1) x 9311] x
      9311", "[(E32///Hexi15/CBB23//GC-1) x E32] x E32". After backcrossed and self
      crossed 1 approximately 2nd, the plants pyramiding Xa23 and IPT genes can be used
      in the program of hybrid rice breeding.

PMID- 15481541
TI  - [A preliminary study on gene expression profile induced by water stress in wheat
      (Triticum aestivum L.) seedling].
AB  - In the present research, suppression subtractive hybridization (SSH) and high
      density membrane techniques were employed to analysis genes induced by water
      stress in wheat seedling at 2-leaf stage. The purpose was to comprehensively
      understand the genetic bases of drought resistance and to find the key genes
      related to drought resistance in wheat. A total of 181 positive clones were
      obtained by screening the SSH library including 1 530 individual recombinant
      clones. The result of the sequence homologous comparison and function querying
      showed that 83.2% differentially expressed genes were high homologous with those
      induced by abiotic or biotic stresses in plant and their functions were to
      protect the cell directly or indirectly from stress strain. Seventeen
      differentially expressed ESTs found first were registered in GenBank. After
      further identifying by reverse Northern, RT-PCR and Northern, the gene expression
      profile induced by water stress in wheat seedling was preliminarily revealed.

PMID- 15481542
TI  - [The structural characteristics, alternative splicing and genetic experession
      analysis of ADP-ribosylation-factor 1 (arf1) in cotton].
AB  - The full-length cDNA,DNA and promoter of ADP-ribosylation-factor 1 (arf1) was
      isolated from Gossypium hirsutum Y18 by means of isocaudarner inverse PCR (II
      PCR) and rapid isolating cDNA 5' unknown sequence and promoter (RICUP)
      established in our lab. Results indicated that the gene is 4 360 bp in size,
      including seven exons and six introns. Interestingly, alterative splicing occurs
      at intron I. Differential processing of intron 1 yields three different
      transcripts with 1 026 bp, 1103 bp and 1 544 bp in sizes, respectively. Arf1
      encodes 181 amino acids. Sequence analysis indicated that sequence upstream
      transcription initiation site of arf1 includes typical initiator, TATA box, CCAAT
      box, GC box and several forward and reverse repeat sequences. And typical
      promoter structures, such as AT-rich sequence and palindrome structure have been
      detected in the sequence downstream transcription initiation site. Southern blot
      analysis indicated that the gene has two copies in the genome of cotton. Northern
      blot confirmed the predominate expression of arf1 in reproductive organs of
      cotton, including bud, flower, fiber and boll. Also, the feature and character of
      arf1 and its promoter have been studied. This study will lay foundation for the
      other research on function of arf1 in the development of reproductive organs in
      cotton.

PMID- 15481543
TI  - [Heteologous expression of Mortierella isabellina delta6 -fatty acid desaturase
      gene in soybean].
AB  - Gamma-linolenic acid (GLA, C18:3delta(6, 9, 12) is one of nutritionally important
      polyunsaturated fatty acids in human and animal diets. Vast majority oilseeds
      crops do not produce GLA. Delta6-fatty acid desaturase (D6D) is the rate-limiting
      enzyme, which catalyzes the conversion of linoleic acid (LA) and alpha-linolenic
      acid (ALA) to GLA and octadecatetraenoic acid (OTA). In this study, a delta6
      fatty acid desaturase gene isolated from Mortierella isabellina was transformed
      into some soybean cultivars Jilin 35, Jilin 47, Suinong 10, Suinong 14 and
      Heinong 37 successfully by agrobacterium-mediated cotylendon node transformation
      system. The results of PCR analysis, Southern blotting and Northern blotting with
      transgenic plants indicated that target gene was integrated into transgenic
      soybean genome and expressed at the level of RNA. Meanwhile, total fatty acids
      were extracted from transgenic seeds and methyl-esterified. Analysis of gas
      chromatograph (GC) showed that a novel peak corresponding to the standard of GLA
      methyl ester was detected, the highest percentage of gamma-lenolenic acid to
      total fatty acids in transgenic seeds was 27. 067%, which indicated that
      Mortierella isabellina delta6-fatty acid desaturase gene was expressed in
      transgenic soybean. It is so far the first report on the expression of delta6
      fatty acid desaturase gene in transgenic soybean in the world.

PMID- 15481544
TI  - [The genetics of human monogenic obesity].
AB  - Obesity is a clinical syndrome caused by genetic and environmental factors and
      has a relatively high heretability. Seven genes, of whose mutations each can
      independently result in severe human obesity, have been cloned. Six of them are
      involved in the appetite controlling by the central nervous system, and one is
      related to the regulation of adipocyte differentiation. Investigations into the
      genetic basis of human obesity are important for understanding the mechanism of
      obesity formation and for design and screening of anti-obesity drugs.

PMID- 15481545
TI  - [A strategy for assessing environmental influence on airway allergy using a
      regression binary tree-based method].
AB  - OBJECTIVE: To clarify the living environment factors that increase the risk of
      allergic sensitization to house dust mites, we applied a regression binary tree
      based method (CART, Classification & Regression Trees) to an epidemiological
      study on airway allergy. The utility of the tree map in personal sanitary
      guidance for preventing allergic sensitization was examined with respect to
      feasibility and validity. SUBJECTS AND METHODS: A questionnaire was given to 386
      healthy adult women, asking them about their individual living environments.
      Also, blood samples were collected to measure Dermatophagoides pteronyssinus (Dp)
      specific IgE, the presence/absence of Dp-sensitization being expressed as
      positive/negative. The questionnaire consisted of nine items on (1) home
      ventilation by keeping windows open, (2) personal or family smoking habits, (3)
      use of air conditioners in hot weather, (4) type of flooring
      (tatami/wooden/carpet) in the living room, (5) visible mold proliferation in the
      kitchen, (6) type of housing (concrete/wooden), (7) residential area (heavy or
      light traffic area) (8) heating system (use of unventilated combustion
      appliances), and (9) frequency of cleaning (every day or less often). There also
      were queries on the past history of airway allergic diseases, such as bronchial
      asthma and allergic rhinitis. CART and a multivariate logistic regression
      analysis (MLRA) were performed. The subjects were first classified into two
      groups, with and without a history of airway allergic diseases (Groups WPH and
      WOPH). In each group, the involvement of living environment factors in Dp
      sensitization was examined using CART and MLRA. RESULTS: In the MLRA study,
      individual living environment factors showed promotional or suppressive effects
      on Dp-sensitization with differences between the two groups. With respect to the
      CART results, the two groups were first split by the factor that had the most
      significant odds ratio for MLRA. In Group WPH, which had a Dp-sensitization risk
      of 19.5%, the first split was by the factor of visible mold proliferation in the
      kitchen into the factor-present group with a risk value of 45.5% and the factor
      absent group with 13.5%. The mold proliferation group was split with reference to
      frequent cleaning, and the risk rose to 75% in the factor-absent group and to
      100% when family smoking habits were reported. Group WOPH (the risk: 10.8%) was
      first split into two groups according to the use of air conditioners in hot
      weather for more than 6 hours a day or less, which showed risk values of 16.7%
      and 6.9%, respectively. The risk of the group that intensively used air
      conditioners fell to 8.3% with tatami as flooring in the living room, and, if
      others, rose to 20.8%. The risk of the factor-lacking group fell to 4.0% without
      wooden flooring. CONCLUSIONS: CART analysis enables us to express complex
      relationships between living environment factors and Dp-sensitization simply by a
      binary regression tree, pointing to preventive strategies that can be flexibly
      changed according to the individual living environments of the subjects.

PMID- 15481546
TI  - [Improvement of mental health and the quality of life after catheter ablation for
      paroxysmal supraventricular tachycardia].
AB  - PURPOSE: The aims of this study were to observe change in subjective symptoms,
      quality of life (QOL) and mental health condition after catheter ablation (CA)
      for paroxysmal supraventricular tachycardia (PSVT) and to assess patient
      evaluation of the treatment. METHODS: The questionnaire was sent to 103 patients
      (86 with the Wolff-Parkinson-White (WPW) syndrome and 27 with atriovetricular
      nodal reentrant tachycardia (AVNRT)), who had received CA from February 1995 to
      January 1999. The question encompassed the condition of the patient, his or her
      evaluation of CA treatment, and a self-rating depression scale (SDS) together
      with social and subjective as well as non-specific physical points. We scored for
      improvement of QOL and SDS. Finally, from 82 patients who participated complete
      responses to the questionnaire were received from 59 (72.0%). The patients (50.5
      +/- 15.8 years old, WPW syndrome; 41, AVNRT; 18) almost all (98.3%) RESULTS: gave
      a positive evaluation of CA. Over half (54.2%) no longer needed hospital
      consultation for any reason while three-quarters (76.3%) were free of life
      limitations. The complete cure rate from physicians was 100%. However, subjective
      symptoms of arrhythmia attack remained in 20.3% of the cases. Social and physical
      QOL were significantly improved after CA (social: < 0.05, physical: < 0.01) and
      the SDS score decreased significantly (< 0.05). 1. Self-awareness frequency of
      tachycardia attack, frequency of going to hospital and life CONCLUSION:
      limitations of PSVT patients decreased after CA. 2. QOL (social and physical QOL)
      and mental health condition significantly improved after CA. 3. Almost all
      patients (98.3%) gave a positive evaluation of CA. 4. Healthcare professionals
      should be aware that not only drug therapy, but also CA is effective for
      improvement of mental health and the QOL of patients with PSVT.

PMID- 15481547
TI  - [Depression and psychosocial factors in alcoholic members of teetotal societies].
AB  - OBJECTIVE: To ascertain-1) the prevalence of depression and psychosocial
      characteristics in alcoholics who are members of teetotal societies, and 2) the
      relationship between depression and psychosocial factors. METHOD: A self-report
      questionnaire survey was conducted of 184 alcoholic members of seven teetotal
      societies in a prefecture in Japan. Questionnaires consisted of items on
      demographics, the self-rating depression scale (SDS), family environment in
      childhood, self-esteem, coping, and sense of coherence (SOC). RESULTS: 1) The
      mean SDS score was 31.8 points in males and 35.8 points in females. Depression
      level for the male sample was equivalent to that for male employees. Coping
      behavior characterized by escape and resignation was more prevalent in the
      employees. Mean scores of both self-esteem (33.3 points) and SOC (118.7 points)
      were lower than in general. 2) SDS was significantly related to length of time
      spent within a teetotal society, self-esteem, SOC, coping behavior characterized
      by resignation and positive approaches to problem solving. The shorter the time
      within the teetotal society, the lower the scores for self-esteem, SOC, and
      coping behavior typified by positive approaches to problem solving; and the
      higher the score for coping behavior characterized by resignation, the higher the
      SDS score. CONCLUSION: The findings of this study suggested that depression in
      alcoholic members of teetotal societies occurred at similar levels to that for
      the general population, but that self-esteem, sense of coherence, and suitable
      coping behaviors were reduced. It was suggested that depression in alcoholics who
      are members of teetotal societies may be associated with short history of
      membership in the group, low sense of coherence, low self-esteem, and
      inappropriate coping behavior.

PMID- 15481548
TI  - [Risk factors associated with onset of urinary incontinence in a community
      dwelling elderly population: a 4-year follow-up study].
AB  - OBJECTIVE: To estimate the risk factors associated with onset of urinary
      incontinence in a rural community-dwelling elderly population. METHODS: The study
      area, village N in Akita Prefecture, is a rural community in which a baseline
      survey of TMIG-LISA (Tokyo Metropolitan Institute of Gerontology, Longitudinal
      and Interdisciplinary Study on Aging) was undertaken in 1996. Among the baseline
      subjects, 760 (314 males and 446 females) community-dwelling elderly people aged
      over 65, who did not suffer from urinary incontinence at entry of the survey were
      selected. This cohort has been followed for four years by multi-dimensional
      medical examination including interviews and physical performance tests,
      conducted on a yearly basis using similar methods to these for the baseline
      survey. RESULTS: After the 4-year follow-up, the incidence of urinary
      incontinence was 7.0% (22/314) in men and 12.3% (55/446) in women. The urinary
      incontinence group (UIG) had a significantly higher age and lower level of
      functional fitness at baseline for both sexes. In the UIG, the men but not the
      women had significantly lower serum levels of albumin and total cholesterol. By
      the logistic model, age (per 1-year increase: OR = 1.23, 95%CI: 1.11-1.38), and
      serum albumin (per 0.1 g/dl increase: OR = 0.70, 95%CI: 0.54-0.88) in men; and
      grip strength (per 1-kg increase: OR = 0.92, 95%CI: 0.86-0.98), social role (per
      1-point decrease: OR = 1.81, 95%CI: 1.19-2.73), BMI (per 1-kg/m2 increase: OR =
      1.10, 95%CI: 1.01-1.20) and smoking status (never smoker = 1.00, 3 = current
      smoker: OR = 7.53, 95%CI: 1.36-41.63) in women were independent variables
      significantly associated with onset of urinary incontinence. CONCLUSIONS:
      Lifestyle and functional fitness are significantly associated with onset of
      urinary incontinence in this population. Our findings suggest that intervention
      programs are needed to improve pelvic floor muscle and to provide social support
      for the elderly.

PMID- 15481549
TI  - [An epidemiological approach to the metabolic syndrome].
AB  - OBJECTIVE: To investigate four risk factors for the metabolic syndrome. METHODS:
      Using the health examination database of a Japanese company, 8,194 middle-aged
      male workers were assessed for the metabolic syndrome with reference to: (1)
      obesity (body mass index > or = 25 kg/m2); (2) hypertension (> or = 140/90 mmHg
      or taking antihypertensive drugs); (3) diabetes (fasting blood glucose > or = 110
      mg/dl); and (4) hyperlipidemia (total cholesterol > or = 220 mg/dl or
      triglyceride > or = 150 mg/dl). (1) Those who had developed the metabolic
      syndrome (n = 148) were retrospectively followed for 5 years. Persistence rates
      for the four risk factors were calculated. (2) Those who had three risk factors
      (n = 1,100) were followed for 5 years to observe the development of metabolic
      syndrome. The incidence rates from Kaplan-Mayer analysis were compared among four
      different patterns for three risk factors. Adjusted hazard ratios (HRs) and their
      corresponding 95% confidence intervals (CIs) were calculated using the Cox's
      proportional hazard RESULTS: (1) The highest persistence rate was found for
      obesity, followed by hyperlipidemia, hypertension, and diabetes. (2) After
      adjusting for age, smoking, drinking, and exercise, significantly higher HRs
      (95%CIs) were found for those with obesity, hypertension, and diabetes (4.4; 2.9
      to approximately 6.9), those with obesity, diabetes, and hyperlipidemia (3.2; 2.1
      to approximately 4.9), and those with obesity, hypertension, and hyperlipidemia
      (2.1; 1.4 to approximately 3.0), compared with those with hypertension, diabetes,
      and hyperlipidemia. CONCLUSIONS: Obesity may be the key to developing the
      metabolic syndrome in those who demonstrate three risk factors.

PMID- 15481550
TI  - [Effects of a food delivery service on the nutritional status of elderly persons
      living at home alone].
AB  - OBJECTIVE: The present study was carried out to determine whether a food delivery
      service can improve the nutritional status of elderly persons living at home
      alone. METHODS: The subjects were 74 elderly women (age range, 70-90 years;
      average age 80.2 +/- 3.6 years) living in T town, Miyazaki Prefecture. All were
      independent in activities of daily living and their nutritional status was
      individually evaluated using anthropometric, biochemical and dietary methods. We
      then compared the nutritional status between persons who used the delivery
      service for more than 3 months and persons who lived alone and did not use the
      delivery service or who lived with their families. RESULTS: Based on the
      anthropometric examination, all persons appeared to be in a good nutritional
      state. However, their total serum protein and albumin levels demonstrated some
      undernutrition. Total serum protein, albumin, total cholesterol, and HDL
      cholesterol were all higher in persons who received food from a delivery service
      than in the control group living alone. Persons who lived with their families had
      similar levels as persons using the delivery service. Individuals who lived alone
      tended to eat sweets more frequently than those with their families. The food
      delivery service resulted in a higher consumption of fat. CONCLUSIONS: The
      nutritional status of elderly persons living alone may be improved by dishes high
      in fat delivered for lunch or supper. These results suggest that food delivery
      services run by municipalities are efficient for nutritional care.

PMID- 15481551
TI  - Nasopharyngeal carcinoma treated with precision-oriented radiation therapy
      techniques including intensity-modulated radiotherapy: preliminary results.
AB  - This paper reports preliminary results with intensity-modulated radiotherapy
      (IMRT) in nasopharyngeal carcinoma (NPC). Between August 2000 and May 2001, we
      treated 19 patients with NPC using IMRT. Twelve patients had stage I-II disease
      and seven had stage III-IV disease. Six patients received 9.0-19.8 Gy three
      dimensional conformal radiotherapy (3D-CRT) before IMRT and 18 patients received
      a brachytherapy boost after IMRT. The mean follow-up time was 13.0 months. All
      patients with stage II-IV disease except one received two cycles of
      chemoradiotherapy with cisplatin and 5-fluorouracil (5-FU) during radiotherapy,
      followed by two to four cycles of chemotherapy after radiotherapy. Tumor response
      was assessed using clinical examination and computerized tomography or magnetic
      resonance imaging. The mean doses administered to the gross tumor volume and
      clinical tumor volume were 70.9 Gy and 63.2 Gy, respectively. The mean doses
      administered to the right and left parotid glands were 38.1 Gy and 38.6 Gy,
      respectively. All 19 patients had a complete response of primary and lymph node
      disease. Grade III mucositis developed during chemoradiotherapy in 15 patients
      (79%). In addition, clinical grade I xerostomia was recorded in nine patients,
      grade II in nine, and grade III in one. This study demonstrated that 3D-CRT,
      IMRT, intracavitary brachytherapy, and chemotherapy are effective and safe
      methods to treat NPC. Although IMRT treatment spared parotid gland function, its
      efficacy may be significantly influenced by disease stage and location of the
      neck lymph nodes. More cases and a longer follow-up to assess survival and
      complications are planned.

PMID- 15481552
TI  - Developing a safety and health training model for petrochemical workers.
AB  - The production processes of the petrochemical industry expose workers to high
      potential hazards. Our previous study showed that hazard recognition was closely
      related to worker safety and health training activities. The purpose of this
      study was to establish and validate a safety and health training model. It is
      expected that the training model will help workers to recognize hazards, thereby
      lowering their operating risks. The training model, which included a complete
      training course and follow-up scoring using a questionnaire, was applied to three
      groups of subjects for comparison. Group A had joined our study previously and
      took the training course again at this time. Group B had also joined our previous
      study but did not take this training course. Group C was new to our study and
      took this training course for the first time. Groups A and C (who took the
      training course) had higher cognition and attitude scores than group B (who did
      not take the training course). The training course was a significant factor that
      positively influenced both cognition and attitude scores among managers and
      workers. The training course was more significant for managers while the duration
      of education was more significant for workers.

PMID- 15481553
TI  - Self-care and well-being model for elderly women: a comparison of rural and urban
      areas.
AB  - The purposes of this study were to examine the relationships among age, social
      class, perceived health, self-care, and well-being in urban and rural elderly
      women and to validate and compare two models using these two groups. A causal
      model of self-care and well-being was proposed for this study based on Orem's
      self-care model and empirical data. Data were collected using a survey-interview
      method. Of the 351 elderly women recruited, 159 were in the urban group and 192
      in the rural group. Two models of self-care and well-being were tested using path
      analysis with the LISREL 8 program. The resultant models yielded a Chi-squared of
      1.98 with two degrees of freedom (p = 0.37) in the urban group and a Chi-squared
      of 4.20 with three degrees of freedom (p = 0.24) in the rural group, indicating
      good fit between the data and the two models. These two models provide guidelines
      for community nurses to design appropriate self-care programs for elderly women.

PMID- 15481554
TI  - Factors related to stress in outpatients with permanent colostomies.
AB  - The main purpose of this study was to explore factors related to stress in
      outpatients with permanent colostomies, using a convenience sample. Subjects were
      selected from one medical center in southern Taiwan. The Stress of Colostomy
      Patients Scale and demographic data were collected using questionnaires either at
      the colorectal outpatient department or in the home of colostomy patients.
      Seventy-three subjects with colostomies participated in the study. Other diseases
      and caregivers of colostomy patients influenced overall stress in outpatients
      with permanent colostomies. The five major stressors were: "I have urination
      problems"; "I feel tired easily owing to physical decline"; "I can't travel
      freely because of my colostomy"; "I worry about recurrence of the disease"; and,
      "I suffer from insomnia". This study provides important information for assessing
      the stress level of outpatients with permanent colostomies and for developing
      nursing assessment tools for colostomy patients. To alleviate the overall stress
      of colostomy patients and to help them return to the activities of daily living
      before the operation, health care professionals could design individual nursing
      care plans based on data from assessment tools.

PMID- 15481555
TI  - Clear cell and non-clear cell hepatocellular carcinoma: a case report and
      literature review.
AB  - Clear cell hepatocellular carcinoma (HCC) is an uncommon variant of HCC. It is
      considered to have a better prognosis than non-clear cell HCC, but recent large
      studies show that there is some controversy. DNA image cytometry reveals diploid
      and non-diploid DNA content tumors that have different pleomorphisms and mitosis
      corresponding to different prognoses. Clear cell HCC is classified as focal or
      diffuse. Herein, we report a rare case of a 61-year-old male with two adjacent
      hyper- and hypoechoic hepatic nodules and an alpha-fetoprotein concentration of
      6,370 ng/mL. Pathologic examination of a specimen obtained during wedge
      hepatectomy showed both clear cell and non-clear cell HCC. Bone metastasis was
      later found. We suggest that a patient with clear cell HCC should be followed up
      closely after complete resection.

PMID- 15481556
TI  - Testicular sparing surgery for bilateral epidermoid cysts of the testes: a case
      report.
AB  - We report the case of a 12-year-old boy with bilateral epidermoid cysts of the
      testes diagnosed preoperatively from ultrasonography, magnetic resonance imaging,
      and negative tumor markers. The cysts were treated using bilateral testicular
      sparing surgery through a scrotal approach after intraoperative frozen section.
      We also discuss the diagnosis and management of epidermoid cyst of the testis and
      briefly review the literature.

PMID- 15481557
TI  - Thyroid-associated orbitopathy with superior oblique muscle involvement: a case
      report.
AB  - A 29-year-old male with a 5-year-history of hyperthyroidism complained of
      diplopia and proptosis. After subtotal thyroidectomy, he still had diplopia in a
      certain gaze. Computerized tomography showed inferior rectus muscle enlargement
      in the right eye and inferior rectus, medial rectus, and superior oblique muscle
      enlargement in the left eye. Ocular examination with the cover and uncover test
      revealed hyperphoria and exophoria in the left eye. The upward gaze of the right
      eye was more limited than that of the left eye. Since superior oblique muscle
      involvement in patients with thyroid orbitopathy is quite rare, we discuss its
      effect on ocular motility in patients with thyroid-associated orbitopathy.

PMID- 15481558
TI  - Foreign body stone in the urinary bladder: a case report.
AB  - Bladder calculi rarely form spontaneously and are usually a manifestation of an
      underlying pathologic condition of the lower urinary tract, including voiding
      dysfunction, urinary infection, obstruction, or foreign body retention. However,
      a ruptured Foley balloon-induced bladder stone is an unusual complication of an
      indwelling Foley catheter. We report a case of spinal cord injury with paraplegia
      and bladder stone induced by a fragment of a ruptured Foley balloon. The bladder
      stone and the Foley balloon fragment were successfully removed by cystoscopy. The
      stone was composed of calcium oxalate and calcium phosphate. We report this
      unusual case to raise awareness that it is important to check the integrity of
      the Foley catheter after removal of the tube.

PMID- 15481559
TI  - Effect of aspirin and indomethacin on prostaglandin E2 synthesis in C6 glioma
      cells.
AB  - Prostaglandin E2 (PGE2) plays an important role in immunosuppression and tumor
      growth. PGE2 inhibitors such as aspirin and indomethacin suppress experimental
      tumor growth. Little is known of the relationship between PGE2 synthesis in brain
      tumors and the dose of aspirin or indomethacin. The present study was undertaken
      to evaluate the effect of different doses of aspirin and indomethacin on PGE2
      synthesis in C6 glioma cells. C6 glioma cells were incubated with different
      concentrations (2, 4, and 8 microM) of aspirin and indomethacin for 1, 2, 4, 6,
      8, 12, and 24 hours. Intracellular PGE2 concentration was measured by enzyme
      immunoassay. Each concentration of aspirin and indomethacin effectively inhibited
      PGE2 synthesis. Concentrations of 2, 4, and 8 microM of aspirin significantly
      inhibited PGE2 production at 6, 4, and 1 hour, respectively, and the inhibition
      persisted for more than 24 hours (p < 0.05). Concentrations of 2 and 4 microM of
      indomethacin were effective at 4 and 2 hours (p < 0.05), respectively. However,
      inhibition was not observed beyond 12 hours (p > 0.05). Indomethacin 8 microM was
      effective at 1 hour and the inhibition persisted beyond 24 hours (p < 0.05). Our
      study demonstrates that aspirin and indomethacin inhibit PGE2 synthesis in C6
      glioma cells and that low-dose aspirin is as effective as high-dose aspirin. This
      study may encourage future clinical use of low-dose aspirin in the prevention or
      treatment of brain tumors.

PMID- 15481560
TI  - Epidermal growth factor expression in middle ear cholesteatoma.
AB  - Middle ear cholesteatoma is destructive to auditory ossicles and temporal bone,
      and treatment usually requires surgical removal of all epithelial content.
      Epidermal growth factor (EGF) can stimulate the growth and differentiation of a
      variety of mammalian cells, including epithelial cells. Our study used the avidin
      biotin complex technique to evaluate the expression of EGF in 40 cases of middle
      ear cholesteatoma (active cholesteatoma, 31 cases; inactive cholesteatoma, 9
      cases) and 34 normal postauricular skin samples. In middle ear cholesteatoma, EGF
      was expressed in squamous epithelium in 21 cases (53%), fibroblasts in two cases
      (5%), and cholesteatoma endothelium in two cases (5%). In normal postauricular
      skin, EGF was expressed in squamous epithelium in 14 samples (41%), fibroblasts
      in one sample (3%), and endothelium in none. No statistical difference in EGF
      expression was found between cholesteatoma and normal postauricular skin samples.
      These results show that the distribution of EGF in middle ear cholesteatoma is
      not deranged and that the progression of cholesteatoma might be induced by the
      release of factors from the cholesteatoma matrix via autocrine stimulation, or by
      inflammatory cells of the subepithelial tissue through paracrine stimulation, or
      in both of these ways.

PMID- 15481561
TI  - Comparative study of early childhood high-function autism and developmental mixed
      receptive-expressive language disorder.
AB  - Verbal cognitive profile and general social functioning were compared between two
      groups of children aged 5 to 7 years, one with high-function autism and the other
      with developmental mixed receptive-expressive language disorders. The two groups,
      totaling 50 children, were matched for age and non-verbal IQ (mean, 90). Both
      groups had impaired verbal cognitive profile and social adaptive functioning,
      with no statistically significant differences between the two groups. The
      implications of our findings are discussed. Current preschool and early childhood
      medical-educational intervention programs in Taiwan must design and implement
      curricula in which children with language delay, whether autistic or/not, can
      develop essential social skills.

PMID- 15481562
TI  - Preliminary study of the effect of low-intensity home-based physical therapy in
      chronic stroke patients.
AB  - This study was a preliminary examination of the effect of low-intensity home
      based physical therapy on the performance of activities of daily living (ADL) and
      motor function in patients more than 1 year after stroke. Twenty patients were
      recruited from a community stroke register in Nan-Tou County, Taiwan, to a
      randomized, crossover trial comparing intervention by a physical therapist
      immediately after entry into the trial (Group I) or after a delay of 10 weeks
      (Group II). The intervention consisted of home-based physical therapy once a week
      for 10 weeks. The Barthel Index (BI) and Stroke Rehabilitation Assessment of
      Movement (STREAM) were used as standard measures for ADL and motor function. At
      the first follow-up assessment at 11 weeks, Group I showed greater improvement in
      lower limb motor function than Group II. At the second follow-up assessment at 22
      weeks, Group II showed improvement while Group I had declined. At 22 weeks, the
      motor function of upper limbs, mobility, and ADL performance in Group II had
      improved slightly more than in Group I, but the between-group differences were
      not significant. It appears that low-intensity home-based physical therapy can
      improve lower limb motor function in chronic stroke survivors. Further studies
      will be needed to confirm these findings.

PMID- 15481563
TI  - Indeterminate cell histiocytosis: a case report.
AB  - Indeterminate cell histiocytosis is a rare neoplasm composed of cells with mixed
      characteristics of Langerhans cells and non-Langerhans cells. An otherwise
      healthy, 36-year-old woman presented with asymptomatic generalized papules and
      nodules that had appeared on all four extremities, the trunk, and cheeks in the
      previous 6 months. The lesions were firm, painless, non-pruritic, and slightly
      flesh-yellow or reddish-brown in color. Histopathologic, immunohistochemical
      examination and electron microscopic studies showed characteristic findings of
      indeterminate cell histiocytosis: diffuse proliferative histiocytes infiltrating
      the dermis without epidermotropism or atypia; neoplastic cells expressing markers
      characteristic of both Langerhans cells (CD1a, S-100) and focal
      monocytes/macrophages (Factor XIIIa, CD68); and no Birbeck granules within the
      cytoplasm of the neoplastic cells. Flow cytometry revealed more CD34+ cells in
      the peripheral blood of the patient than in peripheral blood from a control.
      Interestingly, the patient responded favorably to psoralen ultraviolet A-range
      treatment. Herein, we present this case and review the literature.

PMID- 15481564
TI  - Fibro-osseous lesion of the external auditory canal: a case report.
AB  - The aim of this study was to differentiate a novel type of benign circumscribed
      bone lesion of the external auditory canal from lesions described previously,
      such as exostoses and osteomas. We present a 43-year-old male patient who
      suffered from ear discharge of the right ear. Local findings showed bloody
      discharge from his right auditory canal, which was occupied by a mass-like
      tissue. Computerized tomography (CT) carried out before resection of the lesion
      disclosed the absence of a bony connection to the underlying structures. The
      pathologic findings showed lesions consisting of an osteoma-like bone formation
      with sparse osteoblastic areas. Mature lamellar bone and bone marrow containing
      adipose tissue were also noted. There was no evidence of a relationship to the
      cartilaginous tissue or bony structures of the external auditory canal.
      Therefore, we present this rare case and review the reported literature in which
      clinical, CT, surgical, and pathologic findings suggest that this lesion was
      unlike those previously known, and may be related to ossifying reactions in other
      parts of the organism.

PMID- 15481565
TI  - Supraumbilical skin rash and fat necrosis after transcatheter arterial
      chemoembolization: a case report.
AB  - We report the case of a 63-year-old female who had chronic hepatitis C and who
      was diagnosed with hepatocellular carcinoma. Hepatic angiography showed one
      visible and tortuous falciform artery arising as the terminal branch of the left
      hepatic artery. Transcatheter arterial chemoembolization (TACE) was performed via
      the left hepatic artery. The patient developed supraumbilical skin rash with
      local tenderness on the following day. After supportive treatment by a
      dermatologist, the skin rash subsided gradually with sequelae of irregular skin
      surface and one small subcutaneous nodule. Skin biopsy of the lesion 1 year later
      showed fat necrosis with foreign body reaction and fibrosis. We discuss this rare
      complication of TACE and review the literature.

PMID- 15481566
TI  - Post-traumatic ligamentum flavum hematoma: a case report.
AB  - We present the case of a 64-year-old female treated surgically for ligamentum
      flavum hematoma that caused progressive radiculopathy. Initially, she suffered
      from an acute onset of lower back pain. Only a history of minor back injury was
      discovered. She rapidly became unable to walk. Magnetic resonance imaging
      demonstrated an epidural mass lesion at L3 to L4 that was continuous with the
      left ligamentum flavum. The mass was hypointense on T1-weighted images and
      centrally hyperintense and marginally hypointense on T2-weighted images. The
      margin was well enhanced by gadopentetate dimeglumine administration. After
      removal of the mass, the patient's symptoms completely resolved. Before surgery,
      we believe accurate diagnosis of ligamentum flavum hematoma can be based on
      magnetic resonance imaging.

PMID- 15481567
TI  - [Dyspnoea in pregnant female immigrants due to unexpected mitral valve stenosis].
AB  - Three female patients, a 22-year-old Moroccan woman, a 25-year-old Turkish woman
      and a 35-year-old Iraqi woman, became increasingly dyspnoeic during their
      pregnancy; this was a symptom of congestive heart failure due to mitral valve
      stenosis. Since all patients were refractory to medical treatment, they underwent
      invasive therapy by percutaneous transvenous mitral balloon valvotomy (PTMV). In
      two patients this therapy was successful, but in one patient a closed mitral
      valvotomy was needed. All three women delivered healthy infants, two immediately
      following the PTMV; at follow-up 2-4 years later, the women and infants were all
      doing well. The prevalence of mitral valve stenosis in the western world is
      increasing because of changing immigration patterns. When pregnant patients start
      complaining about dyspnoea, especially if they are immigrants, one should be
      aware of the possibility of mitral valve stenosis. PTMV is a safe and successful
      treatment for these patients and is preferred above surgical therapy because of
      its low morbidity and mortality for both mother and foetus. PTMV must be
      performed in a thoracic surgery centre by an experienced team and the X-ray
      exposure should be minimised.

PMID- 15481568
TI  - [The practice guideline 'Peripheral vascular disease' (first revision) from the
      Dutch College of General Practitioners: a response from the perspective of
      general practice].
AB  - The practice guideline 'Peripheral vascular disease' (PVD) from the Dutch College
      of General Practitioners will certainly be of benefit to the Dutch general
      practitioner. Its limited set of simple diagnostic steps can help the general
      practitioner to assess or exclude PVD in patients with intermittent claudication.
      The inclusion of a pretest-posttest probability scheme enhances a clear
      diagnostic process. This guideline differs from the previous one in one important
      aspect. This guideline deals not only with the specific management of peripheral
      arterial disease but also with the management of cardiovascular risk in general.
      In this way the guideline follows the recently changed international attitude
      reflected in the European Guidelines on cardiovascular disease prevention.
      Smoking cessation and exercise therapy continues to be the cornerstone as well as
      the stumbling block of management of most cases of PVD in general practice; a
      challenge for every general practitioner.

PMID- 15481569
TI  - [The practice guideline 'Peripheral vascular disease' (first revision) from the
      Dutch College of General Practitioners: a response from the perspective of
      surgery].
AB  - The practice guideline 'Peripheral vascular disease' is well written and based on
      evidence-based principles. In comparison with the previous guideline considerable
      attention is given to secondary prevention. In this guideline general
      practitioners are more diffident about prescribing statins than vascular
      specialists. This is probably related to the fact that this guideline refers to
      another guideline of the College concerning the treatment of patients with high
      cholesterol concentrations and not to recently-published large studies. The
      guideline advises making a distinction between intermittent claudication stage 2a
      and 2b. This is impractical as the choice of therapy depends on the subjective
      feelings of disability. Some controversy remains with respect to the detection of
      asymptomatic abdominal aneurysms: should there routinely be only physical
      examination or ultrasonographic screening as well? The guideline advises against
      routine ultrasonic screening, which is in line with the view held by the author
      of this commentary.

PMID- 15481570
TI  - [Acetylsalicylic acid for the primary prevention of cardiovascular disease in
      diabetic patients].
AB  - Large-scale trials have shown that primary prevention using acetylsalicylic acid
      is useful in all patients with a cardiovascular risk exceeding 1.5% annually. In
      these patients the benefits of prevention outweigh the risks of bleeding. Almost
      all patients with diabetes mellitus are at high risk of developing cardiovascular
      disease. Additionally, most diabetics have other cardiovascular risks besides
      diabetes, providing further argument for prevention with acetylsalicylic acid.
      Only very few prospective trials have confirmed that acetylsalicylic acid
      treatment in patients with diabetes mellitus reduces their risk of cardiovascular
      disease and myocardial infarction. Treatment with acetylsalicylic acid should be
      considered in all patients with diabetes, especially in view of their decreased
      survival after a cardiovascular event, myocardial infarction in particular. If
      acetylsalicylic acid is contra-indicated treatment with clopidogrel is an
      alternative.

PMID- 15481571
TI  - [Still no indications that the treatment of growth hormone deficient adults with
      growth hormones is unsafe].
AB  - Although more than 100,000 patients worldwide are estimated to have received
      growth-hormone treatment, there are still widespread doubts about the safety
      aspects of growth-hormone treatment of adults with growth-hormone deficiency
      (GHD). The available data are scarce and the follow-up time is short. The data do
      not suggest that growth-hormone treatment increases the incidence or regrowth of
      pituitary adenomas in adults with GHD. Equally there are no data which suggest
      that growth-hormone treatment of adults with GHD increases the incidence of
      cancer, provided that concentrations of the insulin-like growth factor I (IGF-I)
      achieved in the blood remain within the normal range for the age of that patient.
      No increase in diabetes mellitus has been reported following the introduction of
      growth-hormone treatment in adult GHD patients. Insulin sensitivity does not
      appear to change in GHD patients on growth-hormone treatment as long as
      relatively low physiological doses of growth hormone are used. Whether growth
      hormone therapy in adult patients with GHD will prove safe in the long term
      remains to be established.

PMID- 15481572
TI  - [Summary of the practice guideline 'Peripheral vascular disease' (first revision)
      from the Dutch College of General Practitioners].
AB  - Peripheral vascular disease is a manifestation of atherosclerosis and may occur
      with or without signs or symptoms. The local prognosis is worse with signs or
      symptoms. The concomitant atherosclerosis in heart and brain is responsible for
      long-term morbidity and mortality. Absence of signs and symptoms almost excludes
      peripheral vascular disease, but for the diagnosis an ankle-brachial index is
      mandatory. This implies a protocol in general practice. Treatment of peripheral
      vascular disease consists of advice on cardiovascular risk factors, stopping
      smoking, walking exercises, and foot care. For peripheral vascular disease, anti
      thrombotic medication is advised.

PMID- 15481573
TI  - [Diagnostic image (199). A woman with palmar pustulae].
AB  - A 83-year-old woman developed several small abscesses in the palm of her left
      hand, caused by a scattering, infected false aneurysm of the radial artery where
      a catheter had been inserted.

PMID- 15481574
TI  - [Clinical characteristics and management of adolescents admitted to the emergency
      ward for alcohol intoxication in the region of The Hague during the period 1999
      2001].
AB  - OBJECTIVE: To analyse the findings in adolescents between the ages of 12 and 17
      who were admitted to the emergency ward as a result of excessive alcohol
      consumption. DESIGN: Retrospective. METHOD: The clinical characteristics,
      laboratory findings and treatment policy were studied in adolescents between the
      ages of 12 and 17 who were admitted for alcohol intoxication (> or = 1/1000) to
      the emergency wards of Leiden University Medical Centre, Juliana Children's
      Hospital, Haaglanden Medical Centre (Westeinde location) or the Leyenburg
      Hospital (all hospitals in the area of The Hague, The Netherlands) during the
      period 1999-2001. RESULTS: In the three successive years, the number of patients
      was 19, 18 and 51, respectively; there were a total of 58 boys and 30 girls.
      Laboratory determinations and other investigations were carried out and/or
      recorded in varying numbers of patients. The cause of the intoxication was
      usually the consumption of spirits together with friends; 60% of the patients had
      a Glasgow coma score < 15 and 30% were admitted to hospital. In 25% the visit to
      the emergency ward was preceded by an accident in which alcohol played a part.
      Little attention seems to have been paid to aftercare in the form of a follow-up
      visit.

PMID- 15481576
TI  - [Alcohol intoxication in four adolescents].
AB  - Four teenagers, two boys aged 14 and almost 13 years and two girls aged 14.5 and
      15 years, were hospitalised because acute alcohol intoxication was suspected.
      Three of them had only a single instance of excessive alcohol consumption, but
      the 13-year-old boy was admitted twice in three months due to alcohol
      intoxication. The blood alcohol concentration in these adolescents varied between
      1.4 and 2.3 g/l. During admission the patients were treated symptomatically and
      there were no complications. Loss of consciousness occurs at lower blood alcohol
      concentrations in adolescents than in adults. There is also a greater risk of
      mild hypoglycaemia. In case of recurring excessive alcohol consumption, further
      psychosocial counselling is necessary.

PMID- 15481575
TI  - [Successful treatment of three elderly patients suffering from prolonged delirium
      using the cholinesterase inhibitor rivastigmine].
AB  - Delirium is commonly encountered in elderly patients in general hospitals. Most
      patients with delirium respond well within 12 days of commencement of treatment
      with haloperidol. A significant number of patients, however, does not improve.
      Three elderly male patients aged 85, 79 and 81 respectively suffering from
      prolonged delirium and unresponsive to haloperidol or atypical anti-psychotic
      drugs, responded well within days to treatment with rivastigmine--a
      cholinesterase-inhibitor. It was very well tolerated. In The Netherlands
      cholinesterase inhibitors are registered for the symptomatic treatment of
      Alzheimer's disease. There is some evidence, both from animal and human
      experiments, that cholinergic deficiency plays a role in certain types of
      delirium. Therefore treatment of delirium with a cholinesterase-inhibitor seems
      logical. Controlled studies are needed to evaluate the effects of these types of
      drugs in patients with prolonged delirium.

PMID- 15481577
TI  - [Heart failure in general practice: patient characteristics, diagnosis and
      treatment].

PMID- 15481578
TI  - [Better treatment for psychiatric patients avoiding health care: discussion of
      legislation should not be isolated from other factors and considerations].

PMID- 15481579
TI  - [Health Council of the Netherlands advisory report 'Vaccination against
      pertussis'--time for a new vaccine].

PMID- 15481580
TI  - [The mammary duct fistula: a persistent problem that can be treated adequately].

PMID- 15481581
TI  - [Traumatic spinal cord injury and cardiovascular complications due to neurogenic
      shock: a possible threat for functional recovery].

PMID- 15481582
TI  - Roles of FGF-10 on the development of diathrodial limb joints.
AB  - OBJECTIVES: Members of the fibroblast growth (FGF) family of signaling proteins
      are known to play important roles in limb skeletal patterning and in chondrocyte
      proliferation and maturation. Recent work from this laboratory showed that FGF
      members are expressed in limb developing joints. Thus, the present project
      focused on what roles these proteins may have in joint development. METHODS:
      Heparin-coated beads precoated with recombinant FGF-10 or GDF-5 were implanted
      around incipient proximal and distal joints of digits 3 and 4 in Day 6-8 chick
      limb buds in organ culture. Specimens were processed for whole mount in situ
      hybridization using antisense riboprobes encoding chick GDF-5 and FGF-10 or for
      histology analysis at indicated time points. RESULTS: Whole mount in situ
      hybridization revealed that FGF-10 is expressed, and its transcripts are present,
      during interzone formation. Gain-of-function experiment revealed that exogenous
      FGF-10 caused down-regulation of expression of FGF-10 as well as GDF-5. In
      specimens continuously treated with exogenous FGF-10, joint formation was
      markedly impaired and often resulted in fusion of contiguous cartilaginous
      phalanges. CONCLUSIONS: The study provides evidence for the first time that FGF
      10 is expressed during joint development in addition to FGF-2 and FGF-4. The
      precise roles of these signaling molecules will require further work. However, it
      is possible to speculate that these proteins, singly or in concert, may favor
      proliferation of mesenchymal cells during interzone formation. Our data also show
      that prolonged treatment with exogenous FGF-10 leads to joint impairment and
      fusion. Similar defects were observed previously when other joint-associated
      proteins were experimentally manipulated, indicating that a fine balance among
      distinct regulatory molecules is needed for normal joint formation.

PMID- 15481583
TI  - Expression and purification of salivary anti-HIV protein from transfected cells
      in culture.

PMID- 15481584
TI  - Surface treatment of titanium for RD immobilization.

PMID- 15481585
TI  - B-cell lymphoma presenting a gingival enlargement.

PMID- 15481586
TI  - Detection of Mycobacterium avium subspecies paratuberculosis in Swiss dairy
      cattle by culture and serology.
AB  - Faecal samples from 186 dairy cows representing ten commercial dairy herds with
      sporadic clinical paratuberculosis (group A), and from 100 dairy cows from herds
      without a history of paratuberculosis (group B) were cultured for Mycobacterium
      avium subspecies paratuberculosis (MAP). Two different decontamination methods, a
      NaOH/oxalic acid method and treatment with 0.75% hexadecylpyridinium chloride
      (HPC) were performed prior to inoculation of Loewenstein-Jensen agar slants with
      and without mycobactin. Cultures were incubated for 16 weeks. Acid-fast staining
      bacteria were identified as MAP on the basis of mycobactin dependency and by PCR
      RFLP analysis of the IS 1311-insertion element of M. avium. MAP was grown from 15
      out of 186 group A animals (8.1%) whereas faecal culture for MAP was consistently
      negative in group B. The growth rate of MAP was significantly higher (8.1% vs.
      1.6%) and the contamination rate of cultures was significantly lower (17.6% vs.
      21.5%) in faecal samples decontaminated with NaOH/oxalic acid than with HPC
      treated faecal samples (p<0.01, McNemar's test). Atypical mycobacteria which were
      grown from 46.8% of NaOH/oxalic acid treated specimens were not obtained from any
      of the HPC-treated samples. A commercial ELISA with MAP-lipoarabinomannan as the
      antigen was used to detect MAP-antibodies in unabsorbed sera from all animals.
      The percentage of ELISA-positive cows was 16.8%. Overall agreement between
      antibody detection and MAP-positive faecal culture was 15.4%.

PMID- 15481587
TI  - [Comparison of antimicrobial resistance pattern of selected respiratory tract
      pathogens isolated from different animal species].
AB  - The antibiotic resistance pattern of respiratory tract pathogens isolated of
      different animal species suffering from respiratory tract diseases has been
      investigated by antibiograms performed by agar diffusion test. The results show
      that the resistance situation in Switzerland is favourable compared with studies
      from other countries. However, high resistance rates were found in certain
      species: 61% of Streptococcus spp. were resistant to erythromycin and 44% to
      tetracycline, 59% of Bordetella bronchiseptica were resistant to ampicillin and
      50% of Mannheimia (Pasteurella) haemolytica were multiresistant to tetracycline,
      ampicillin and streptomycine. The gram negative isolates were widely resistant to
      streptomycine.

PMID- 15481588
TI  - [Acquired cardiac diseases in the dog: a retrospective analysis].
AB  - To document the frequency of the different acquired cardiac diseases in the
      referring area of the University of Zurich, records of 474 dogs were
      retrospectively analysed. Most common were valvular diseases, predominantly
      atrioventricular valve endocardiosis (49.4%), myocardial diseases, predominantly
      dilated cardiomyopathy (21.1%), pericardial effusion (12.4%), mainly due to
      neoplasia or idiopathic pericarditis, and cardiac neoplasia without pericardial
      effusion (7.0%). Rare to very rare diagnoses were dirofilariosis (2.5%),
      endocarditis (1.1%, only 2 of these valvular), hypertrophic cardiomyopathy (0.6%)
      and infectious pericarditis (0.4%). Arrhythmias were found in 145 dogs, mainly
      tachyarrhythmias, and most commonly associated with dilated cardiomyopathy.
      Relevant concomitant diseases were tracheobronchial collapse and
      hyperadrenocorticism in dogs with mitral endocardiosis. Knowing prevalence and
      causes of the various cardiac and the complicating non-cardiac diseases with
      clinical similarities is important for formulating diagnosis and differential
      diagnosis.

PMID- 15481589
TI  - Signs of metastatic disease on thoracic radiographs of dogs suffering from
      mammary gland tumours: a retrospective study (1990-1998).
AB  - A mammary gland tumour (MGT) was clinically diagnosed in 136 dogs. Histologically
      71% were malignant and 29% benign. Intrathoracic metastatic disease was noted or
      suspected radiographically in 13.5% of the dogs with malignant and in 2.5% of the
      dogs with benign MGT. Six dogs with malignant MGT were necropsied, 5 had
      pulmonary metastases but only 1 had radiographic signs of intrathoracic
      metastatic disease. We conclude that radiographs are not very sensitive for
      detection of early intrathoracic metastatic disease of MGT.

PMID- 15481592
TI  - Beyond the hot issue: nurses must get involved.

PMID- 15481597
TI  - Experience in Iraq makes nurse anesthetist appreciate the simple things in life.

PMID- 15481598
TI  - A nurse is a nurse! Really?

PMID- 15481601
TI  - Journey to Magnet Hospital Designation.

PMID- 15481602
TI  - Acute stroke in the United States.

PMID- 15481603
TI  - Clinical features of Waldenstrom macroglobulinemia in Korea.
AB  - BACKGROUND: Waldenstrom macroglobulinemia (WM) is a lymphoproliferative disorder
      characterized by monoclonal IgM. Its rarity makes it difficult to know the
      clinical manifestations and outcomes of patients with WM. METHODS: The clinical
      records of 13 patients diagnosed with WM between 1983 and 2003 were reviewed, and
      12 patients were eligible. RESULTS: The median age was 57 years (range, 40 to
      85), and the male to female ratio was 2. B symptoms and hyperviscosity requiring
      plasmapheresis existed in 5 and 4 patients, respectively, at the time of
      diagnosis. Hepatomegaly and splenomegaly were detected in 5 and 3 patients,
      respectively. Sites of extranodal involvement were bone (3) and lung (1) in 3
      patients. The peripheral neuropathy was complicated in 3 patients. (Ed note:
      check this sentence.) Cryoglobulin was checked in 6 patients and it was detected
      in 3 of them. The median concentration of serum IgM was 4.2 g/dL (0.7-6.2). The
      median albumin, hemoglobin, WBC, and platelet levels were 2.8 g/dL, 8 g/dL,
      5,400/microL, and 138,000/microL, respectively. One patient had transitional cell
      carcinoma concomitantly, and one patient developed small cell lung cancer. Of the
      11 patients receiving chemotherapy (7-chlorambucil, 2-melphalan, 1
      cyclophosphamide, 1-CHOP), 4 patients showed the objective responses including 2
      complete remissions, but they all ultimately relapsed. The response rate of
      second-line therapy was 14% (1/7). After a median follow-up of 20 months, 3
      patients were still alive with disease. The median overall and progression-free
      survival were 24 months (95% confidence interval (CI): 5-43) and 24 months (95%
      CI: 8-40), respectively. CONCLUSION: The initial high levels of serum IgM and
      severe anemia reflect a lack of suspicion of WM at the early stage. Careful
      suspicion and proper diagnostic approaches will allow more patients to show an
      improved outcome.

PMID- 15481605
TI  - Heat shock protein expression in adenosine triphosphate depleted renal epithelial
      cells.
AB  - BACKGROUND: In this study, the putative interactions between apoptosis and heat
      shock proteins disturbed as a result of ATP depletion were investigated as a
      hypoxia model. METHODS: The direct cellular damages were assessed by the release
      of LDH from the cytoplasm of the human tubular epithelial cells (HK-2 cells)
      following ATP depletion. The Bcl-2/Bax mRNA expression ratio, used as an index to
      assess to what extent apoptosis contributed to tubular cell damage, and the
      expressions of HSP 90, 72 and 27 in relation to the Bcl-2/Bax ratio in the
      ischemic model, as parameters of their functional contributions to tubule cell
      damage, were also studied. Heat preconditioning (HS) was performed at 43 degrees
      C in a temperature-regulated water bath for 1 h. RESULTS: The release of LDH due
      to ATP depletion was not significantly increased in HK-2 cells compared to the
      control, but was slightly increased in heat preconditioned cells compared to non
      heat preconditioned cells, but the difference was not statistically significant
      (6.33 +/- 0.57 U/L vs. 8.67 +/- 2.52 U/L, p>0.05). The Bcl-2/ Bax mRNA expression
      ratio increased progressively from the control to the heat preconditioned and ATP
      depleted cells (control; 100%, ATP depletion; 154 +/- 6%, heat preconditioning;
      212 +/- 6%, heat preconditioning and ATP depletion; 421 +/- 8%). No contribution
      of heat preconditioning and ATP depletion was observed on the expressions of
      HSP90 and HSP27. However, HSP72 expression was prominent by ATP depletion,
      especially after heat preconditioning. CONCLUSION: There may be a possibility
      that the preservation of cytolytic damage and an increase in the Bcl-2/Bax mRNA
      expression ratio is related to the increase of HSP72 in ATP depletion as a
      hypoxia model.

PMID- 15481604
TI  - Conformational transitions and glycation of serum albumin in patients with
      minimal-change glomerulopathy.
AB  - BACKGROUND: There has been a lack of study on the structural changes of serum
      albumin in patients with minimal change disease (MCD). To determine whether
      glycation and/or conformational transitions of albumin are involved in the
      pathogenesis of albuminuria, nine patients with MCD were enrolled in a
      prospective follow-up study for comparison of these parameters in serum albumin
      during the remission and relapse of nephrotic syndrome. METHODS: Circular
      dichroism measurements were made with purified albumin. Ellipticities at each
      wavelength were transformed to mean residue ellipticity. Monosaccharide
      composition was analyzed by high-pH anion-exchange chromatography with pulsed
      amperometric detection. RESULTS: There was no difference in the proportions of
      alpha-helix, beta-conformation, and beta-turn of albumin between the sera of
      control patients and those with nephrotic syndrome. However, the proportion of
      the random configuration was slightly higher in the plasma albumin of patients in
      relapse than in those in remission. The proportion of the random configuration
      was lower in the albumin of the serum than in the urine of patients with
      nephrotic syndrome, but there was no difference in the proportions of alpha
      helix, beta-conformation, and beta-tum of albumin between their plasma and urine.
      CONCLUSION: Our results suggest that conformational changes in albumin are
      involved in albuminuria in patients with MCD.

PMID- 15481606
TI  - Clinical characteristics of hypervagotonic sinus node dysfunction.
AB  - BACKGROUND: Sinus node dysfunction (SND) is caused not only by intrinsic sinus
      node disease, but also by the extrinsic factors. Among the extrinsic factors,
      autonomic imbalance is most common. Symptomatic SND usually requires permanent
      pacemaker therapy. However, the clinical characteristics and patient response to
      medical therapy for hypervagotonic SND have not been properly clarified.
      MATERIALS AND METHODS: Thirty two patients (14 men, 18 women, 51 +/- 14 years)
      with hypervagotonic SND were included in this study, but those patients who had
      taken calcium antagonists, beta-blockers or other antiarrhythmic drugs were
      excluded. Hypervagotonic SND was diagnosed if the abnormal electrophysiologic
      properties of the sinus node were normalized after the administration of atropine
      (0.04 mg/kg). RESULTS: The presenting arrhythmias were 16 cases of sinus
      bradycardia (50.0%), 12 of sinus pause (37.5%), 3 of sinoatrial block (9.4%) and
      1 of tachy-bradycardia (3.1%). Nine (28.1%) patients had hypertension, 7 (21.9%)
      smoked, 2 (6.3%) had diabetes mellitus, and 1 (3.1%) had hypercholesterolemia.
      Among the patients, 3 had no remarkable symptoms, 13 had dizziness, 7 had
      syncope, 3 had weakness and 6 had shortness of breath. Twenty five (78.1%)
      patients were treated with theophylline, 1 patient with tachy-bradycardia
      syndrome was treated with digoxin and propafenone, and 6 (18.8%) were treated
      with no medication. During the 43 +/- 28 month follow-up, 25 patients remained
      asymptomatic, but 6 who took no medication developed mild dizziness. One patient
      needed permanent pacemaker implantation owing to recurrent syncope despite of
      theophylline treatment. CONCLUSION: These results show that hypervagotonic SND
      has a benign course and most of the patients can be managed safely without
      implanting a pacemaker. (Ed note: I like the abstract. It is short and direct, as
      it should be.)

PMID- 15481607
TI  - Clinical outcome of bacteremic spontaneous bacterial peritonitis due to extended
      spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae.
AB  - BACKGROUND: This study was conducted to evaluate the risk factors for infection
      and clinical outcomes of bacteremic spontaneous bacterial peritonitis (SBP) due
      to ESBL-producing E. coli and K. pneumoniae, in patients with advanced liver
      cirrhosis. METHODS: The ESBL production was determined by NCCLS guidelines and/or
      double-disk synergy tests, on stored E. coil and K. pneumoniae blood isolates
      collected between 1998 and 2002. Of the patients with advanced liver cirrhosis,
      15 case patients, with SBP due to ESBL-producers, were compared with 30 matched
      controls, with SBP due to non-ESBL-producers. RESULTS: There were no significant
      differences in age, sex, Child-Pugh scores, or APACHE II scores between the two
      groups. Significant factors associated with infection by ESBL-producing
      organisms, according to univariate analysis, were: ICU care, indwelling urinary
      catheter, central venous catheterization, an invasive procedure within the
      previous 72 hours, and prior use of antibiotics within the previous 30 days. When
      assessing the clinical response at 72 hours after the initial antimicrobial
      therapy, the treatment failure rate was significantly higher in the ESBL group
      (73.3% vs. 16.7%, p<0.001). Also, overall 30-day mortality rates were 60% (9/15)
      in the ESBL groups and 23.3% (7/30) in the control group (p=0.015). CONCLUSION:
      Among patients with advanced liver cirrhosis, bacteremic SBP due to ESBL
      producing E. coil and K. pneumoniae was associated with adverse outcomes, and
      significantly higher mortality.

PMID- 15481608
TI  - Relationship of hemodynamic indices and prognosis in patients with liver
      cirrhosis.
AB  - BACKGROUND: Hyperdynamic circulation due to reduced peripheral vascular
      resistance and increased cardiac output, and the development of portal
      hypertension are the hemodynamic changes observed in patients with liver
      cirrhosis. Such hemodynamic abnormalities appear in patients with late stage
      liver cirrhosis. Therefore, hemodynamic indices, which represent hyperdynamic
      circulation and portal hypertension, are significant for the prognosis of
      patients with liver cirrhosis. The aim of this study was to determine the
      hemodynamic indices associated with the prognosis of patients with liver
      cirrhosis. METHODS: A total of 103 patients diagnosed with liver cirrhosis
      between December 1999 and June 2003, with a mean follow-up period of 73 weeks,
      ranging from 7 to 168 weeks, were recruited. Using Child-Pugh classification, the
      mean arterial pressure, heart rate and hepatic venous pressure gradient (HVPG)
      were measured. The indices of Doppler ultrasonography, including the portal and
      splenic venous flows, and the resistance of the hepatic, splenic, and renal
      arteries were also measured using the arterial pulsatility index (PI). The
      prognostic values of these indices were determined by their comparison with the
      patient survivals. RESULTS: Significant hemodynamic indices for a bad prognosis
      were high HVPG (> or = 15 mmHg) and renal arterial PI (> or = 1.14)(p<0.05). A
      Child-Pugh score > or = 10 was important for a poor prognosis (p<0.05).
      CONCLUSION: Severe portal hypertension (HVPG > or = 15 mmHg) and high renal
      arterial resistance (PI +/- 1.14) were valuable hemodynamic indices for the
      prognosis of patients with liver cirrhosis. Therefore, it was concluded that the
      measurement of these hemodynamic indices, in addition to the Child-Pugh
      classification, is helpful in the prognosis of patients with liver cirrhosis.

PMID- 15481609
TI  - Incidence of and risk factors for bundle branch block in adults older than 40
      years.
AB  - BACKGROUND: In the general population, the incidence of bundle branch block (BBB)
      is relatively low, and its effects on long-term prognosis have not been
      established. Previous studies on the incidence and correlation of BBB to clinical
      factors have produced conflicting results. However, the incidence of BBB was
      strongly related to age. This study aimed to describe the incidence of and risk
      factors for BBB in Korea. METHODS: In this study, 14,540 adults (male
      6,573/female 7,967) > or = 40 years old received screening tests for general
      health between April and December 2000. Participants answered questionnaires and
      underwent examinations, which included blood pressure, electrocardiogram (ECG),
      total cholesterol and fasting glucose. The data analysis was performed using SPSS
      10.0 for windows. RESULTS: The incidences of complete right bundle branch block
      (CRBBB) were 1.5 and 2.9% in people older than 40 and 65 years, respectively.
      Approximately 38.0% of individuals with CRBBB were older than 65 years. The
      incidence of CRBBB was higher in men than women at all age groups was highest in
      those aged 75-79 years. Males, advancing age (> or = 65 years), hypertension and
      diabetes mellitus (DM) were associated with an increased risk of CRBBB. The
      incidences of complete left bundle branch block (LBBB) and bifascicular bundle
      branch block (BBBB) were 0.1 and 0.08% and 0.3 and 0.2% in those older than 40
      and 65 years, respectively. Approximately 71.4 and 58.3% of individuals with LBBB
      and BBBB, respectively, were older than 65 years. Advancing age and cardiac
      disease were associated with an increased risk of LBBB. Advancing age was
      associated with an increased risk of BBBB. The most potent risk factor for BBB in
      this study was advancing age. CONCLUSION: The incidences of BBB were 1.7 and 3.4%
      in those older than 40 and 65 years respectively. Bundle branch block correlates
      strongly with age, and is common in the older ages groups. These findings support
      the theory that bundle branch block is a marker of slowly progressing
      degenerative diseases.

PMID- 15481612
TI  - Myelodysplastic syndrome with erythroid aplasia following pure red cell aplasia.
AB  - Myelodysplastic syndrome (MDS) with erythroid aplasia is a very rare disorder
      that has not been clearly defined. We experienced a case of pure red cell aplasia
      (PRCA), which evolved to MDS with erythroid aplasia. A 59-year-old male with
      transfusion-dependent PRCA was referred to our hospital for an evaluation of
      newly developed thrombocytopenia. Two years ago, PRCA was diagnosed by the
      laboratory findings and a bone marrow examination, which showed no evidence of
      any myelodysplastic features and thymoma. Upon admission, the bone marrow
      findings showed marked hypercellularity. with numerous dysplastic features in the
      three lineages including erythroid hypoplasia. These findings were compatible
      with a diagnosis of MDS with red cell aplasia. It is very interesting that the
      PRCA evolved to MDS with red cell aplasia, which strongly suggests an autoimmune
      mechanism for the development of MDS.

PMID- 15481611
TI  - Lymphocytic hypophysitis with diabetes insipidus: improvement by
      methylprednisolone pulse therapy.
AB  - Lymphocytic hypophysitis is a rare inflammatory disorder in the pituitary gland.
      The lesion is usually confined to the adenohypophysis. Although the involvement
      of the posterior pituitary gland or the stalk is rare, such patients with
      diabetes insipidus have been reported. Surgery has been used to make the
      definitive diagnosis. Recent studies suggest, however, that the pathologic
      diagnosis may not be necessary always. We reported a case of Lymphocytic
      hypophysitis managed by methylprednisolone pulse therapy. A 50-year-old
      premenopausal woman with Lymphocytic hypophysitis and diabetes insipidus was
      treated with methylprednisolone pulse therapy. Her adenopituitary lesion
      disappeared and the diabetes insipidus resolved. The optimal management for
      patients with lymphocytic hypophysitis may be the high index of the suspicion
      prior to the extensive surgical resection. In addition, methylprednisolone pulse
      therapy may improve the clinical and MRI findings.

PMID- 15481610
TI  - A novel method of brachytherapy using local delivery of 99mTc-HMPAO for coronary
      stent restenosis.
AB  - BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) is a matter
      that still remains to be resolved. Herein, the inhibitory effect of locally
      delivered 99mTc-HMPAO (hexamethyl propylene amine oxime) on neointimal
      hyperplasia after coronary stenting was examined in a pocine model, and its
      safety and efficacy observed in patients with coronary stent restenosis. METHODS:
      After a stent overdilation injury, local radioisotope delivery using 99mTc-HMPAO
      was applied to one coronary artery (Group I) and control therapy to another
      (Group II) in each of 10 pigs. Follow-up coronary angiogram (CAG) and
      histopathologic assessment were performed 4 weeks after stenting. Eleven patients
      (10 males and one female, 62.4 +/- 5.7 years of age) underwent local
      administration of 30 mCi/ 2 mL 99mTc-HMPAO shortly after PCI, via a Dispatch
      Catheter, followed by a whole body scan to evaluate the distribution of the 99mTc
      HMPAO, as well as a thallium-201 (TI-201) myocardial scan to evaluate myocardial
      perfusion. The major adverse cardiac events (MACE) were assessed during a one
      year clinical follow-up. RESULTS: On histopathological analysis, the neointimal
      areas were 1.2 +/- 0.6 and 2.7 +/- 0.4 mm2 (p=0.002), and the histopathological
      areas of stenosis were 27.16.3 and 53.4 +/- 5.2% in Groups I and II (p=0.001),
      respectively. In the clinical study, there was no in-hospital MACE. On a
      quantitative coronary angiographic analysis, the minimal luminal diameter was
      increased from 0.4 +/- 0.3 to 2.9 +/- 0.2 mm, and diameter stenosis decreased
      from 84.2 +/- 9.5 to 16.3 +/- 11.0% following PCI. Follow-up CAG was performed in
      9 cases (81.8%) and restenosis occurred in 2 (22.2%). On a follow-up CAG, the
      minimal luminal diameter, diameter stenosis rate, lumen loss and loss index were
      2.0 +/- 0.8 mm, 27.7 +/- 2.9%, 0.7 +/- 0.7 mm and 0.2 +/- 0.3, respectively.
      During the one-year clinical follow-up there were no cases of death or acute MI,
      but two cases of target vessel revascularization (18.2%). CONCLUSION: Local
      delivery of 99mTc-HMPAO, a novel radiotherapy, can be used safely and effectively
      for coronary stent restenosis.

PMID- 15481613
TI  - Acute exacerbation of chronic hepatitis B during thalidomide therapy for multiple
      myeloma: a case report.
AB  - We report a case of acute fatal exacerbation of chronic hepatitis B in a 50-year
      old man with multiple myeloma being treated with thalidomide. The patient had a
      medical history of chronic hepatitis B and was diagnosed with stage IIIA multiple
      myeloma. He suffered two episodes of transient transaminitis of unknown origin
      after successive autologous stem cell transplantations. Spontaneous resolutions
      of the transaminitis were observed without special management. At that time, PCR
      of hepatitis B virus (HBV) were all-negative. After 5-months' administration of
      thalidomide for the second relapse of the multiple myeloma, he suddenly
      experienced dizziness and jaundice. The level of HBV DNA was 1,641 pg/mL and the
      serologic tests for other viruses were negative. Despite conventional supportive
      care, he expired due to septic shock caused by Klebsiella pneumonia. Based on the
      stable disease status of the multiple myeloma and exclusion of other hepatotoxic
      agents, it was assumed that the exacerbation of the hepatitis B virus during the
      thalidomide therapy preceded the bacterial sepsis. With the increased use of
      thalidomide in cancer treatment, cautious monitoring of the viral burden should
      be performed in patients with chronic hepatitis B.

PMID- 15481614
TI  - Postsplenectomy recurrence of thrombocytopenia with an accessory spleen.
AB  - Autoimmune thrombocytopenic purpura (AITP) is an autoimmune disorder that results
      from antiplatelet autoantibodies; these autoantibodies cause platelet destruction
      in the reticluoendothelial system. Oral corticosteroid therapy is the first line
      treatment. Splenectomy is the major treatment modality after the failure of more
      conservative medical therapy. Approximately 15% of the patients will relapse
      either soon after splenectomy or, as is less common, many years later. The
      presence of an accessory spleen should be sought. We experienced a patient with a
      known diagnosis of autoimmune thrombocytopenic purpura who had a worsening
      thrombocytopenia 11 years after splenectomy. This patient was diagnosed with an
      accessory spleen. Accessory splenectomy was performed with only a transient
      elevation of the platelets. We report here on this case with a review of the
      literature.

PMID- 15481615
TI  - Late local urticaria as a long-term sequela of allergen-specific immunotherapy.
AB  - Local reaction to allergen-specific immunotherapy (SIT) usually appears within 30
      minutes, but cases with exercise-induced urticaria at the SIT site 2-3 weeks
      after the last allergen injection have been reported. A 28-year-old man was
      treated with house dust mite-SIT for 5 years, due to asthma when he was an 11
      year-old boy. On a treadmill exercise test for 50 minutes, erythema, swelling,
      and pruritus occurred at the SIT site, which lasted for one hour. There was no
      evidence of complement activation, and the skin biopsy specimens showed no
      apparent difference between the lesion and normal sites in the distribution of
      inflammatory cells and in mast cell degranulation. However, the morphine, but not
      the histamine, skin test responses were increased after the exercise. There must
      be a remaining long-term sequela of the SIT, including an increased releasability
      of mast cells, even after more than 10 years.

PMID- 15481616
TI  - Diabetes care.

PMID- 15481617
TI  - How to test-drive medical software.

PMID- 15481618
TI  - How to cut A/R.

PMID- 15481619
TI  - Can you be forced to testify against a colleague?

PMID- 15481620
TI  - Making "part-time" work for everyone.

PMID- 15481621
TI  - It sounded good at the time.

PMID- 15481622
TI  - When patients want to buy Meds online.

PMID- 15481623
TI  - Steer patients away from these online drugs.

PMID- 15481624
TI  - Starting a practice. The final steps.

PMID- 15481625
TI  - My first year: tough, but I made it.

PMID- 15481626
TI  - If you drop hospital care.

PMID- 15481627
TI  - Comparison of cardiac troponin T and troponin I assays--implications of
      analytical and biochemical differences on clinical performance.
AB  - The usefulness of cardiac troponins for detection of myocardial cell necrosis and
      risk stratification has been established beyond doubt. Cardiac troponin testing
      is a key diagnostic element for the diagnosis and management of patients with
      acute coronary syndromes without ST segment elevation and is increasingly used in
      non-coronary diseases to indicate prognostically important cardiac damage. Given
      the biochemical and analytical differences of cTnT and cTnI there is ongoing
      controversy regarding the comparability and clinical performance of cTnT and
      cTnI. cTnT and cTnI are both expressed in cardiomyocytes but differ with respect
      to biochemical and analytical characteristics. While minor differences of
      analytical precision or biochemical properties are not relevant for diagnosis and
      management of patients with acute coronary syndromes and most diseases with non
      coronary related elevations of cardiac troponins, these differences may be
      amplified in patients with chronic renal failure. In fact, recent studies in
      patients with end-stage renal disease under chronic hemodialysis have readdressed
      the issue whether cTnT and cTnI are really comparable. The present review will
      provide a state-of-the-art overview on the performance of cardiac troponins in
      acute coronary disease and other clinical conditions.

PMID- 15481629
TI  - Evolving techniques for monitoring clotting in plasma and whole blood samples.
AB  - New models of hemostatic function emphasize the importance of clotting factor
      interactions with cells and highlight the central event of thrombin production.
      As the coagulation cascade has evolved into a scheme of overlapping phases of
      initiation, amplification and propagation, the relevance of plasma based
      coagulation assays are being brought into question. Since platelets are critical
      to both amplification and propagation of the thrombin signal, assays performed in
      the absence of platelets would appear to completely miss these events. The lack
      of sensitivity to platelet influences may explain the inability of the
      prothrombin time (PT) and the partial thromboplastin time (PTT) to detect/reflect
      the therapeutic and clinical effects of agents such as recombinant FVIIa. This
      article reviews several evolving technologies for measuring thrombin generation
      and hemostatic function in samples of plasma and whole blood. Such assays may
      better reflect global hemostasis and hold potential for detecting hypo- and hyper
      hemostatic states as well as monitoring both hemostatic and anticoagulant agents.

PMID- 15481628
TI  - Monitoring of hemostatic status in four patients being treated with recombinant
      factor VIIa.
AB  - Recombinant Factor VIIa (rVIIa) is a potent hemostatic agent for the management
      of refractory bleeding in patients with Factor VII deficiency or Factor VIII
      inhibitors. While the current recommended dose is usually effective, the most
      appropriate dose remains a subject of debate. Since factor VII levels and
      shortening of the pro-thrombin time do not appear to correlate with response, an
      appropriate laboratory marker of clinical response has not been identified. In
      this article we report changes noted in thrombin generation, platelet function
      and clot structure in blood from patients treated with rVIIa. Thrombin generation
      was assessed via a thrombin generation time (TGT) assay using a Hemodyne HAS
      instrument. Changes in clot structure were assessed as changes in clot elastic
      modulus in the HAS, changes in maximum amplitude in the TEG and changes in
      maximum clot firmness in the ROTEG. The cases presented confirmed improvement in
      thrombin generation with administration of rVIIa. The cases also illustrate that:
      a) in the factor VII deficient patient, 25% of the 90 microg/kg dose is
      sufficient to totally correct the defect, b) patients with high level factor VIII
      inhibitors may require significantly more than the recommended dose of 90
      microg/kg, c) thrombin generation may not be completely corrected despite
      dramatic shortening of the prothrombin time, and d) increasing rVIIa doses does
      not by itself ensure improved thrombin generation.

PMID- 15481630
TI  - Comparison of different salivary and fecal antibodies for the diagnosis of celiac
      disease.
AB  - To investigate the detectability and expressiveness of salivary and fecal anti
      gliadin (AGA), anti-endomysium (EMA) and anti-tissue-transglutaminase (ATA)
      antibodies, 127 salivary and 160 fecal samples of healthy volunteers and salivary
      and fecal samples of 17 patients with histologically proven and 9 patients with
      suggested celiac disease were investigated in this study. With all salivary
      parameters and fecal IgA AGA, IgM AGA, IgA EMA and IgG EMA, healthy volunteers
      and patients showed partially overlapping results. The most promising results in
      our study with higher concentrations in patients with celiac disease were
      obtained by fecal scIgA AGA and a combined determination of fecal IgA AGA, IgG
      AGA and IgM AGA. Further investigations should be performed with fecal IgA EMA
      and scIgA ATA based on human recombinant tissue-transglutaminase. One patient
      with histologically proven celiac disease had normal serological but high fecal
      scIgA AGA and scIgA ATA values. This patient emphasizes the importance of fecal
      antibody determination for the diagnosis of celiac disease, at least in patients
      with suggested celiac disease and negative serum antibodies.

PMID- 15481631
TI  - Platelet activation in heart failure.
AB  - Heart failure is a common disease in aging western populations. Not only severe
      but even mild to moderate heart failure is associated with increasing risk for
      stroke. This can partly be attributed to concomitant atrial fibrillation, a well
      known risk factor for stroke. Furthermore, the increased risk for thromboembolic
      events in congestive heart failure has been attributed to a hypercoagulable state
      including formation of intraventricular thrombi. However, more recently, enhanced
      platelet activation has been described in patients with heart failure in sinus
      rhythm. Vascular endothelial dysfunction and reduced formation of the platelet
      inhibitor nitric oxide appear to contribute to platelet activation in heart
      failure. This review article summarizes the historical knowledge of abnormal
      platelet function in heart failure, focuses on pathophysiological changes in
      heart failure which could influence platelet activation, and discusses drug
      regimens investigated in heart failure to reduce platelet activation either by
      direct anti-platelet effects or by modulating the release of platelet inhibiting
      substances.

PMID- 15481632
TI  - Intact and total proinsulin: new aspects for diagnosis and treatment of type 2
      diabetes mellitus and insulin resistance.
AB  - Proinsulin, the precursor of insulin during physiological insulin production, has
      been demonstrated in the past to stimulate PAI-1 secretion and consecutively
      block fibrinolysis. Therefore, proinsulin is contributing as an independent
      factor to the increased cardiovascular risk of patients with type 2 diabetes.
      However, development of insulin resistance in the course of type 2 diabetes leads
      to increased insulin demands and finally to an impairment of beta-cell function
      in later disease stages. Appearance of intact proinsulin in the peripheral blood
      has been shown to be a good laboratory marker for this phenomenon since it
      indicates an exhaustion of the cleavage capacity of the intracellular processing
      enzymes. However, the close relation of the two pathophysiological entities also
      makes it a very specific marker for insulin resistance per se. During the past
      years, new immunoassays have been developed that are able to distinguish between
      intact proinsulin and its specific and unspecific cleavage products. Use of these
      assays in recent epidemiological and intervention studies has helped to get a
      better understanding about beta-cell dysfunction and its relation to insulin
      resistance and cardiovascular risk. In a large cross-sectional study with 4270
      orally treated patients, elevation of fasting intact proinsulin was very closely
      related to insulin resistance, as assessed by iv glucose tolerance test in a
      subgroup, and by HOMA analysis in the entire patient population. Effective
      treatment of insulin resistance (e.g. with thiazolidindiones) led to a decrease
      in elevated proinsulin levels and to a decrease of the cardiovascular risk
      profile, while the levels remained high during sulfonylurea therapy. These
      results suggest to reconsider intact and total proinsulin as valuable diagnostic
      tools in diagnosis and treatment of type 2 diabetes. Based on the published data
      of the new specific immunoassays, patients with elevated intact proinsulin levels
      (> 10 pmol/L) should be regarded and treated as being insulin-resistant, while
      elevation of total proinsulin (>45 pmol/l) may help to identify the high
      cardiovascular risk patients. Both assays can thus be used to assess beta-cell
      function, to facilitate the selection of the most promising therapy, and may also
      serve to monitor treatment success in the further course of the disease.

PMID- 15481633
TI  - Use of the enzyme method for antibody identification.
AB  - Enzyme methods for red blood cell antibody testing may have two goals: detection
      of weak antibodies by increasing the strength of the reactions and
      differentiation of the antibodies in an antibody mixture by abolishing the
      reaction of antibodies against enzyme-labile antigens. We analyzed the phenotype
      listing sheets of all lots of one year (expiration date in 2002) of 8 products (5
      manufacturers) (together 130 worksheets). The aim was to find out how often some
      antibodies could only be detected after enzyme treatment, when there is an
      additional antibody against one of the following enzyme-labile antigens in the
      patient's serum: Fya, Fyb, M, N, S and s. If there is one of these antibodies
      against an enzyme-labile antigen, an additional antibody against one of the
      following enzyme-stable antigens D, C, E, c, e, CW, K, Kpa, Jsa, Jka, Jkb, Lea,
      Leb, P1, Lua cannot be detected on average in 20% of the panels. Moreover, in a
      further 37% of the panels there is no red blood cell suspension carrying the Kpa,
      in 44% none carrying the Jsa and in 19% no one carrying the Lua antigen. On the
      other hand, an antibody against one of the high-incidence antigens k, Kpb, Jsb or
      Lub can be detected in each of the 130 panels, also if there is an additional
      antibody directed against one of the above-mentioned enzyme-labile antigens. As
      also nowadays in some antibody identification panels antibodies against some
      enzyme-stable antigens might be covered by antibodies against enzyme-labile
      antigens, the enzyme method can be a helpful completion in antibody
      differentiation in some sera with multiple antibodies.

PMID- 15481634
TI  - Free thyroxine measured with equilibrium dialysis and nine immunoassays decreases
      in late pregnancy.
AB  - We measured free thyroxine in sera from 29 women in the ninth month of pregnancy.
      We used the reference method, equilibrium dialysis, and nine immunoassays. The
      bias between immunoassay and dialysis results was insignificant or modest. With
      all methods, the results were in the lower part of the non-pregnant female
      reference interval or below the lower limit of this interval: 10 results with the
      equilibrium dialysis assay and from 4 to 18 results with the nine immunoassays.
      Method-specific reference intervals should be determined during pregnancy to be
      in a position to quantify not only hypothyroidism but also hyperthyroidism and to
      adjust an appropriate T4 treatment.

PMID- 15481635
TI  - Characterization of aged osteocalcin fragments derived from bone resorption.
AB  - INTRODUCTION: Osteocalcin (OC) is a small bone matrix protein exclusively found
      in mineralized tissue. OC measured in serum or plasma provides an index of bone
      formation. In the present study a sensitive inhibition ELISA was established that
      could quantify fragments derived from the OC Mid-region in human urine. METHODS:
      The ELISA was based on a monoclonal antibody directed against residues 21-29 of
      human OC (Mid-OC Urine ELISA). OC fragments were isolated from human urine by
      immunoaffinity chromatography. OC fragments were purified further by reversed
      phase high performance chromatography for characterization by N-terminal
      sequencing and mass-spectrometry. OC fragments were assayed in bone cell culture
      supernatants and in serum and urine from patients undergoing anti-resorptive
      bisphosphonate therapy using the Mid-OC urine ELISA. RESULTS AND CONCLUSION: It
      was demonstrated that the release of OC fragments was highly correlated with
      osteoclast-mediated pit formation (r2= 0.89) and with an established marker of
      bone resorption (CTX; r2=0.91). Mid-OC values were decreased markedly after 3 and
      10 days of anti-resorptive bisphosphonate treatment further indicating that the
      marker reflects bone resorption. The molecular characterization revealed that
      most of these molecules were less than 15 amino acids in length and many
      contained modified aspartyl residues (D-aspartyl and isoaspartyl) characteristic
      of aged proteins. The presence of such modifications shows that these molecules
      have resided in the bone matrix for an extended period and thus they cannot be
      derived directly from bone formation. In conclusion, these findings demonstrate
      that OC-fragments are released during osteoclastic bone resorption and that the
      quantification of specific age-modified OC fragments can provide an index of bone
      resorption.

PMID- 15481636
TI  - The significance of laboratory testing for the German diagnosis-related group
      system--the systematic evaluation of comorbidities of relevance to case
      reimbursement and continued development of the DRG Watchdog software.
AB  - The launch of the G-DRG system version 2004 made it necessary to update our
      former studies on the importance of laboratory testing (Clin Lab 2002;48:327
      333). Using a systematic search algorithm, we established a total of 2,828
      comorbidities, the ICD coding of which has a positive effect on case
      reimbursement, thus helping to secure hospital revenue. 62% of these
      comorbidities were found to depend exclusively or predominantly on laboratory
      testing. On average, one such comorbidity can be said to influence approximately
      100 DRGs (range 2 to 226). In order to gain a clearer idea of the practical
      benefit of such "hits", amounting to several 100,000s, we selected about 5% of
      them for illustration with a computer program called DRG Watchdog. This program
      shows just how much additional reimbursement can be achieved for a specific DRG
      upon the ICD coding of a specific comorbidity. The program is freely available on
      the Internet at www.trillium.de and enjoys more than 100 search runs per day.

PMID- 15481637
TI  - Post-challenge hyperglycaemia rather than fasting hyperglycaemia is an
      independent risk factor of cardiovascular disease events.
AB  - Evidence accumulated from several large-scale epidemiological and intervention
      studies strongly indicates that hyperglycaemia and specifically post-challenge
      hyperglycaemia is an independent factor related to the increased risks of
      cardiovascular disease. The DECODE (Diabetes Epidemiology: Collaborative analysis
      Of Diagnostic criteria in Europe) study has de-emphasized the importance of
      fasting glucose, in contrast to post-challenge hyperglycaemia, as the principal
      measurable determinant of glycaemic exposure contributing to the risk of
      cardiovascular disease in Type 2 diabetes and even in non-diabetic subjects. The
      study, based on five Finnish DECODE study cohorts, demonstrated that in subjects
      without previous myocardial infarction, 2-h post-challenge glucose after an oral
      glucose tolerance test was a stronger predictor of the risk of serious coronary
      heart disease events than fasting glucose. Post-challenge hyperglycaemia was
      identified as an independent risk factor for cardiovascular disease also in
      Cardiovascular Health Study and the Framingham Offspring Study. It seems fair to
      conclude that post-challenge glucose is likely to be an independent
      cardiovascular risk factor. The mechanism for the increased risk in the incidence
      and mortality related to post-challenge hyperglycaemia has been speculated. To
      recognize that post-challenge hyperglycaemia is an important risk factor for
      cardiovascular disease may be of a significant preventive importance.

PMID- 15481638
TI  - Serum prolactin in human immunodeficiency virus infection.
AB  - Patients infected with human immunodeficiency virus (HIV) have higher serum
      prolactin compared to healthy controls but this is controversial. As part of a
      laboratory audit investigating the interference of macroprolactin in our
      prolactin assay, we investigated whether low biological activity macroprolactin
      could account for the increased serum prolactin concentrations observed in HIV
      infection. We, therefore, compared serum total prolactin and free prolactin in 32
      subjects infected with HIV (HIV+ve) with 52 subjects not infected with HIV (HIV
      ve). Serum total prolactin concentrations were similar in HIV+ve and HIV-ve
      patients [median (95% confidence limits); 167.0 (122.4 - 313.8) vs 206.5 (187.8 -
      248.4) mU/L respectively]. Serum free prolactin concentrations were lower (p
      <0.005) in HIV+ve subjects than in HIV-ve subjects [112.0 (91.1-141.8) vs 171.0
      (154.5 - 200.9) mU/L respectively; p<0.0005]. These results are consistent with
      the notion that low biological activity macroprolactin contributes to circulating
      prolactin concentrations in HIV+ve subjects.

PMID- 15481639
TI  - Rosa rugosa attenuates diabetic oxidative stress in rats with streptozotocin
      induced diabetes.
AB  - The effects of Rosa rugosa on diabetic oxidative stress were investigated using
      rats with streptozotocin (STZ)-induced diabetes. The diabetic rats showed less
      body weight gain and heavier kidney and liver weights than normal rats, while the
      oral administration of Rosa rugosa at a dose of 100 or 200 mg/kg body weight/day
      for 20 days attenuated the physiological changes induced by diabetes. In
      addition, administrating Rosa rugosa to diabetic rats resulted in significant and
      dose-dependent decreases in the serum glucose and glycosylated protein levels,
      implying that Rosa rugosa improves the abnormal glucose metabolism that leads to
      oxidative stress. Diabetic rats had higher serum levels of superoxide and
      nitrite/nitrate. However, the administration of Rosa rugosa dose-dependently
      reduced the over-production of radicals associated with diabetes, suggesting Rosa
      rugosa is a radical scavenger that would play a crucial role in protecting
      against diabetic oxidative stress. Rosa rugosa significantly and dose-dependently
      reduced thiobarbituric acid-reactive substance levels in serum, hepatic and renal
      mitochondria, implying that Rosa rugosa would alleviate the oxidative stress
      associated with diabetes by inhibiting lipid peroxidation. This study provides
      evidence that Rosa rugosa has potential as a treatment for diabetes through
      attenuating oxidative stress induced by the diabetic condition.

PMID- 15481640
TI  - Administration of Ginseng radix decreases nitric oxide synthase expression in the
      hippocampus of streptozotocin-induced diabetic rats.
AB  - Nitric oxide (NO) is synthesized from L-arginine by nitric oxide synthase (NOS).
      Alternation of NOS expression is implicated in the pathogenesis of numerous
      secondary complications of diabetes. Aqueous extract of Ginseng radix has
      traditionally been used for the various disorders including diabetes. In this
      study, the effect of Ginseng radix on the NOS expression in the hippocampus of
      streptozotocin (STZ)-induced diabetic rats was investigated via nicotinamide
      adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Enhanced NOS
      expression was detected in the hippocampus of diabetic rats and administration of
      Ginseng radix suppressed NOS expression. Ginseng radix may aid the treatment of
      central nervous system complications in diabetes.

PMID- 15481641
TI  - Mechanisms of hepatoprotection of Terminalia catappa L. extract on D
      Galactosamine-induced liver damage.
AB  - The hepatoprotective effects of the extract of Terminalia catappa L. leaves (TCE)
      against D-Galactosamine (D-GalN)-induced liver injury and the mechanisms
      underlying its protection were studied. In acute hepatic injury test, it was
      found that serum ALT activity was remarkably increased (3.35-fold) after
      injection of D-GalN in mice. But with oral pretreatment of TCE (20, 50 and 100
      mg/kg/d) for 7days, change in serum ALT was notably reversed. In primary cultured
      hepatocytes from fetal mice, it was found that cell viability was decreased by
      45.0% after addition of D-GalN, while incubation with TCE (0.1, 0.5 and 1.0
      mg/ml) for 36 hours could prevent the decrease in a dose-dependent manner.
      Meanwhile, D-GalN-induced both the increase of AST level (1.9-fold) and the
      decrease of SOD activity (48.0%) in supernatant of primary cultured hepatocytes
      could also be inhibited by pretreatment with TCE. In order to study the possible
      mechanisms underlying its hepatoprotective effects, one effective component
      separated from TCE, 2alpha, 3beta, 23-trihydroxyursane-12-en-28-oic acid (DHUA),
      was used to determine anti-mitochondrial swelling activity and superoxide
      radicals scavenging activity in vitro. It was found that at the concentration
      range of 50-500 micromol/L DHUA, Ca2+ -induced mitochondrial swelling was dose
      dependently inhibited, and superoxide radicals scavenging activity was also shown
      in a dose-dependent manner. It was concluded that TCE has hepatoprotective
      activity and the mechanisms underlying its protective effects may be related to
      the direct mitochondrion protection and strong scavenging activity on reactive
      oxygen species (ROS).

PMID- 15481642
TI  - The effects of alpha-viniferin on adjuvant-induced arthritis in rats.
AB  - This study was performed to assess the efficacy of alpha-viniferin (Carex humilis
      Leyss) on adjuvant-induced arthritis in rats. Adjuvant arthritis was induced by a
      single subcutaneous injection of 0.1 ml complete Freund's adjuvant (CFA)
      containing 7.5 mg Mycobacterium butyricum suspended in 1 ml sterile paraffin oil
      into the right hind paw. Forty female Sprague-Dawley rats were injected. Righting
      reflex was uniformly lost and considered to be the initial point of arthritis
      development on day 7 after CFA injection. Rats were divided into four groups, and
      upon development of arthritis, tested groups were orally administered 3 or 10
      mg/kg alpha-viniferin or 10 mg/kg ketoprofen every day for 14 days. The control
      group was orally administered 2 ml of physiological saline solution. Bone mineral
      density (BMD), radiological changes and edematous volumes were measured for 35
      days. Alpha-viniferin suppressed the development of inflammatory edema, and
      inhibited the bone destruction, noted with a decrease in BMD (p < 0.05). Hind paw
      edema volume, BMD and radiological changes did not differ significantly in the
      ketoprofen and alpha-viniferin groups during the entire study period. In
      conclusion, alpha-viniferin suppressed arthritic inflammation and bony change in
      rats.

PMID- 15481643
TI  - Evaluation of analgesic, antipyretic activity and toxicity study of Bryonia
      laciniosa in mice and rats.
AB  - Analgesic, antipyretic activity and toxicity study of the leaves of Bryonia
      laciniosa Linn. (Family: Cucurbitaceae) was evaluated in the standard animal
      models. The methanol extract of Bryonia laciniosa (MEBL) was evaluated by hot
      plate and acetic acid-induced writhing methods to assess analgesic activity. The
      antipyretic activity of the extract was also evaluated by normal body temperature
      and yeast-induced hyperpyrexia. The extract showed significant analgesic and
      antipyretic activity. The MEBL was further evaluated for toxicity at the doses of
      125 and 250 mg/kg administered orally for 14 days in rats. At the end of
      experiments, the blood, liver function and kidney metabolism were observed. The
      hematological profile and different biochemical parameters such as SGOT, SGPT and
      ALP were estimated. The present study revealed that MEBL exhibited significant
      analgesic and antipyretic activity in the tested experimental animal models. The
      toxicity study indicates that the extract is not toxic at the tested doses.

PMID- 15481644
TI  - Effects of traditional Chinese medicines on serum lipid profiles and homocysteine
      in the ovariectomized rats.
AB  - To investigate the effects of the traditional Chinese medicines, kuei-lu-erh
      hsien-chiao and chia-wei-hsiao-yao-san, on the cardiovascular systems of mimic
      menopausal rats, five groups were formed: group 1 (the control group) was given a
      sham operation and received distilled water, while groups 2, 3, 4 and 5 were
      ovariectomized and received distilled water, kuei-lu-erh-hsien-chiao, chia-wei
      hsiao-yao-san and 17-beta-estradiol, respectively, for4 months. Our results
      demonstrated that the mean differences of the estrogen levels in groups 3 or 5
      were significantly higher than those of group 2. These data suggest that there
      might be some estrogen-like substances in kuei-lu-erh-hsien-chiao. However, the
      function of these estrogen-like substances was unknown. The mean differences of
      the triglyceride (TG) levels, high-density lipoprotein cholesterol (HDL-C)
      levels, low-density lipoprotein cholesterol (LDL-C) levels, and the ratios of
      TC/HDL-C and LDL-C/HDL-C in groups 1, 3, 4 and 5 were not significantly different
      from those in group 2. The mean differences of the total cholesterol (TC) levels
      in group 5 were significantly higher than those in group 2 (p < 0.05), but no
      obvious difference of the TC levels was found between groups 2 and 4.
      Nevertheless, the mean differences of the homocysteine (Hcy) levels in groups 4
      and 5 were statistically lower than those of group 2. Therefore, administration
      of chia-wei-hsiao-yao-san declines the Hcy levels in OVX rats and does not affect
      the TC levels in these animals. In conclusion, our results indicate that chia-wei
      hsiao-yao-san shows a more profound effect than 17-beta-estradiol in the
      prevention of atherosclerosis in these OVX rats.

PMID- 15481645
TI  - Evaluation of the radioprotective action of geriforte in mice exposed to
      different doses of gamma-radiation.
AB  - The effect of 5, 10, 20, 40 and 80 mg/kg b. wt. of hydroalcoholic extract of
      geriforte (an Ayurvedic herbal medicine) administered intraperitoneally was
      studied on the radiation-induced mortality in mice exposed to 10 Gy of gamma
      radiation. Treatment of mice with different doses of geriforte consecutively for
      5 days before irradiation delayed the onset of mortality and reduced the symptoms
      of radiation sickness when compared with the non-drug treated irradiated
      controls. A maximum protection was observed for 10 mg/kg geriforte, where a
      highest number of survivors were reported by 30 days post-irradiation and further
      experiments were carried out using this dose of geriforte. The mice were treated
      with 10 mg/kg b. wt. geriforte or double distilled water (DDW) and exposed to 7,
      8, 9, 10 and 11 Gy of gamma radiation and observed for the induction of symptoms
      of radiation sickness and mortality up to 30 days post-irradiation. The geriforte
      treatment protected the mice against the GI death as well as bone marrow deaths
      and the dose reduction factor (DRF) was found to be 1.14. Toxicity study showed
      that geriforte was non-toxic up to a dose of 4250 mg/kg, where no drug-induced
      mortality was observed. The LD50 dose of geriforte was found to be 4750 mg/kg b.
      wt. To understand the mechanism of action of geriforte, free radical scavenging
      activity of the drug was evaluated. Geriforte was found to scavenge *OH, O2*-
      ABTS*+ and NO* in a dose-dependent manner. Our study demonstrates that geriforte
      is a good radioprotective agent and the optimum protective dose of 10 mg/kg was
      1/475th of the LD50 dose.

PMID- 15481646
TI  - In vitro stimulation of granulosa cells by a combination of different active
      ingredients of unkei-to.
AB  - Unkei-to is widely used in traditional Japanese herbal medicine for its ovulation
      inducing effect. In the present study, we investigated the in vivo effects of
      unkei-to and its compounds on the steroidogenesis and cytokine secretion in human
      granulosa cells. Unkei-to stimulated the secretions of 17beta-estradiol and
      progesterone from highly luteinized granulosa cells obtained from in vitro
      fertilization patients; the stimulated effect on estradiol secretion occurred
      with 0.3 microg/ml, while a significant effect on progesterone secretion was
      obtained at 10 microg/ml. The unkei-to stimulation of estradiol secretion could
      be accounted for by the effects of its ingredients, Shakuyaku (paeoniae radix,
      Paeonia lactiflora Pallas) and Keihi (cinnamomi cortex, Cinnamomum cassia Blume);
      while dose response curves for unkei-to and Keihi to induce progesterone
      production were superimposable. Exposure of the cells to unkei-to caused dose
      dependent increases in the concentrations of interleukin (IL)-1beta, IL-6 and IL
      8 in the culture medium. Similar results were obtained when cells were incubated
      with the ingredient Ninjin (ginseng radix, Panax ginseng C.A. Meyer), but not
      Shakuyaku and Keihi. These results indicate that unkei-to has direct stimulatory
      effects on human granulosa cells to stimulate the steroidogenesis and secretion
      of cytokines (IL-1, IL-6 and IL-8). The various beneficial actions of unkei-to on
      the ovary may result from a combination of different ingredient herbs with
      different stimulatory effects on both steroidogenesis and the ovulatory process
      within the ovary, as well as stimulatory effect on the hypothalamus-pituitary
      axis.

PMID- 15481647
TI  - Regression of hepatocellular carcinoma spontaneous or herbal medicine related?
AB  - Hepatocellular carcinoma is one of the most common causes of death from cancer in
      Taiwan. Treatments for this disease include surgical resection, transcatheter
      arterial embolization, chemoembolization and systemic chemotherapy. Without
      treatment, the prognosis of hepatocellular carcinoma is poor, and mortality
      continues to be significant even in patients with small tumors detected during
      follow-up. For patients in Taiwan with advanced hepatocellular carcinoma,
      traditional herbal medicine is frequently used. However, neither the overall
      prevalence of this therapy nor its efficacy has been studied systematically.
      Spontaneous regression of cancer, although rare, may occur, but the mechanism
      leading to regression is still far from understood. Here, we report a case of
      hepatocellular carcinoma with complete regression after taking herbal medicine.
      We cannot be certain how significant the herbal preparation was in the regression
      of the hepatocellular carcinoma, but the regression of the tumor provides us a
      reason and hope for further research.

PMID- 15481648
TI  - Lindera strychnifolia is protective against post-ischemic myocardial dysfunction
      through scavenging hydroxyl radicals and opening the mitochondrial KATP channels
      in isolated rat hearts.
AB  - Lindera strychnifolia (tendai-uyaku), a medicinal plant, has long been used for
      the treatment of cardiac, renal and rheumatic diseases in Japan. We aim to
      clarify (1) whether L. strychnifolia is protective against post-ischemic
      myocardial dysfunction, and (2) whether its effect is related to scavenging
      hydroxyl radicals and opening the mitochondrial KATP channels in isolated rat
      hearts. Male Sprague-Dawley rats were orally given 1 ml/day of L. strychnifolia,
      which was extracted from 0.75 and 1.5 g/kg of roots of L. strychnifolia for 4
      days. The rat hearts were excised and perfused on a Langendorff apparatus with
      Krebs-Henseleit solution with a gas mixture of 95% O2 and 5% CO2. The hearts were
      paced at 320 beats/min except during ischemia. Left ventricular developed
      pressure (LVDP, mmHg), +/- dP/dt (mmHg/sec) and coronary flow (ml/min) were
      continuously monitored. All hearts were perfused for a total of 120 minutes
      consisting of a 30-minute pre-ischemic period followed by 30 minutes of global
      ischemia and 60 minutes of reperfusion with or without 5-HD, a mitochondrial KATP
      channel blocker. The levels of lactate, LDH and 2,5-DHBA, an indicator of
      hydroxyl radicals, in the perfusate during reperfusion period were also measured.
      Treatment with L. strychnifolia significantly improved LVDP and +/- dP/dt without
      altering coronary flow during reperfusion. The 100 microM of 5-HD in Krebs
      Henseleit solution was perfused during the 10 minutes of pre-ischemic periods.
      Pretreatment with 5-HD abolished the improvement of LVDP and +/- dP/dt by L.
      strychnifolia. L. strychnifolia significantly attenuated the levels of lactate,
      LDH and 2,5-DHBA during reperfusion, and which were restored by pretreatment with
      5-HD. In conclusion, L. strychnifolia is protective against post-ischemic left
      ventricular dysfunction through scavenging hydroxyl radicals and opening the KATP
      channels in the isolated rat heart.

PMID- 15481649
TI  - Polygalae radix extract protects cultured rat granule cells against damage
      induced by NMDA.
AB  - Polygalae Radix (PR) from Polygala tenuifolia (Polygalaceae) is traditionally
      used in China and Korea, as this herb has a sedative, anti-inflammatory and
      antibacterial agent. To extend our understanding of the pharmacological actions
      of PR in the CNS on the basis of its CNS inhibitory effect, the present study
      examined whether PR has the neuroprotective action against N-methyl-D-aspartate
      (NMDA)-induced cell death in primarily cultured rat cerebellar granule neurons.
      PR, over a concentration range of 0.05 to 5 microg/ml, inhibited NMDA (1 mM)
      induced neuronal cell death, which was measured by a trypan blue exclusion test
      and a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay.
      PR (0.5 microg/ml) inhibited glutamate release into medium induced by NMDA (1
      mM), which was measured by HPLC. Pre-treatment of PR (0.5 microg/ml) inhibited
      NMDA (1 mM)-induced elevation of intracellular Ca2+ concentration ([Ca2+]i),
      which was measured by a fluorescent dye, Fura 2-AM, and generation of reactive
      oxygen species (ROS). These results suggest that PR prevents NMDA-induced
      neuronal cell damage in vitro.

PMID- 15481650
TI  - Clinical assessment of usefulness, effectiveness and safety of jackyakamcho-tang
      (shaoyaogancao-tang) on muscle spasm and pain: a case series.
AB  - This study is a retrospective single case series. Two hundred and thirty-seven
      patients were treated with jackyakamcho-tang (JKT) for relief of muscle spasm and
      pain; 81 of them were included in analysis. (The others were excluded because of
      insufficient medical records to confirm the diagnosis or assess the response.)
      There were 29 patients with nocturnal leg cramps, 28 with cervical spondylosis,
      13 with thalamic pain and 11 with carpal tunnel syndrome, for which the
      effectiveness was assessed as 86.2%, 60.7%, 45.5% and 72.8%, respectively.
      Adverse effects (indigestion, diarrhea or edema) were seen in 11.1% of the total
      patients, but severe cases were only 3.7%. Taking the effectiveness and the
      safety into consideration, the usefulness was assessed as 86.2%, 57.1%, 53.9% and
      72.8% for treating nocturnal leg cramps, cervical spondylosis, thalamic pain and
      carpal tunnel syndrome, respectively. In conclusion, we suggest that JKT is a
      useful herbal medicine with analgesic and anti-spasmodic effects.

PMID- 15481651
TI  - Changes in serum tumor necrosis factor (TNF-alpha) with kami-shoyo-san
      administration in depressed climacteric patients.
AB  - An herbal medicine (kampo) is widely used to prevent or treat climacteric
      symptoms. In order to investigate the potential involvement of tumor necrosis
      factor (TNF)-alpha in susceptibility to mood disorder in climacteric women and to
      clarify the relationship between immune function and the efficacy of herbal
      medicine, we compared serum TNF-alpha levels in two treated groups, with and
      without concurrent use of herbal medicine. This study included 113 consecutive
      depressed menopausal patients who visited the gynecological and psychosomatic
      medicine outpatient clinic of the Osaka Medical College Hospital in Japan. Fifty
      eight patients were administered kami-shoyo-san according to the definition of
      above sho. In contrast, 55 patients who were different in sho of kami-shoyo-san
      were administered antidepressants. Hamilton Rating Scale for depression (HAM-D)
      scores were determined at baseline and 12 weeks after starting treatment
      (endpoint). TNF-alpha concentrations were analyzed before and after 12 weeks of
      treatment. Kami-shoyo-san significantly increased plasma concentrations of TNF
      alpha after 12 weeks of treatment, to 17.22 +/- 6.13 pg/ml from a baseline level
      of 14.16 +/- 6.27 pg/ml (p = 0.048). The percent change in plasma concentration
      of TNF-alpha differed significantly between the kami-shoyo-san therapy group and
      the antidepressant therapy group at 4 weeks (12.0 +/- 7.8% and -1.22 +/- 0.25%,
      respectively, p < 0.01), 8 weeks (19.7 +/- 3.4% and -2.45 +/- 0.86%,
      respectively, p < 0.01), and 12 weeks (21.3 +/- 5.4% and -6.81 +/- 2.2%,
      respectively, p < 0.001). We found in this study that kami-shoyo-san, an herbal
      medicine, increased plasma TNF-alpha levels in depressed menopausal patients.
      Cytokines may play various roles in mood and emotional status via the central
      nervous system and may be regulated by herbal medicines, although the
      interactions are very complex.

PMID- 15481652
TI  - Development of the meridian-visualizing system that superimposes a bio-signal
      upon a body image.
AB  - The precise selection and the identification of acupuncture points are essential
      for the diagnosis and treatment of patients in Oriental medicine. In this study,
      we have developed a meridian identification system using Single-Power Alternating
      Current (SPAC), which discriminates between true acupoints and non-acupoints. The
      SPAC system is not affected by skin resistance or pressure and is more accurate
      than the existing meridian location system, which uses direct current (DC)
      excitation current. The accuracy of the meridian location is ensured with the
      SPAC system because it has the highest sensitivity and the lowest effect on the
      human body. A microprocessor is used to enhance reliability and increase the
      accuracy of the SPAC measurements. Current distribution is displayed using an
      image that overlays the measured skin current on the body image. The positions of
      the acupoints are then displayed on the body image. This method visualizes the
      meridian by measuring skin current with an improved electrode using the acupoint
      discrimination system. A computer display shows the transmitted current as a
      color related to the electrode position. We demonstrated that by changing the
      point of measurement on the skin and tracing the electrode on the screen, it is
      possible to visualize acupoints and meridian phenomena using the color display.

PMID- 15481653
TI  - Effect of reflexology on EEG--a nonlinear approach.
AB  - Reflexology is a 4000-year-old art of healing practiced in ancient India, China
      and Egypt. In the beginning of the 20th century, it spread to the Western world.
      Reflexologic clinics and massage centers can be found all around the world. In
      spite of the widespread popularity, to the best of our knowledge, no serious
      research work has been done in this area, although much scientific research work
      has been carried out in other Eastern techniques like meditation and yoga. This
      is why a humble attempt is done in this work to quantitatively assess the effect
      of reflexological stimulation from a systems point of view. In this work,
      nonlinear techniques have been used to assess the complexity of EEG with and
      without reflexological stimulation. We prefer the nonlinear approach, as we
      believe that the effects are taking place in a subtle way, since there is no
      direct correlation between reflexological points and modern neuroanatomy.

PMID- 15481654
TI  - New York City incident plan comes under criticism.

PMID- 15481655
TI  - Maggots: are you a medical advocate for the elderly?

PMID- 15481656
TI  - Find the value.

PMID- 15481657
TI  - Are you heart smart?
AB  - Heart attacks may be a leading killer of emergency-service providers, but many of
      the contributing risk factors can be addressed through prudent lifestyle
      practices. Of all businesses and industries, emergency services generally have
      more knowledge, time and/or flexibility to exercise and actively participate in
      healthy lifestyles. Perhaps more emphasis should be placed on healthy living than
      on benefits that deal with the results of unhealthy lifestyles. Stop smoking,
      drink sensibly, eat a healthy diet and exercise. Until next time ... be safe!

PMID- 15481658
TI  - Where duty ends: the perils and pitfalls of off-duty response.

PMID- 15481659
TI  - Pulseless electrical activity.

PMID- 15481660
TI  - Cardiogenic shock.
AB  - Cardiogenic shock is a pathophysiologic cascade that often leads to death.
      Although there has been a dramatic decrease in the cases of cardiogenic shock
      since the 1970s, the mortality rate of those patients who are diagnosed with
      cardiogenic shock remains as high as 50% to 80%. As stated throughout the
      article, cardiogenic shock in its later stages cannot be reversed, but clinical
      signs and symptoms of the syndrome may be identified early enough to prevent a
      patient from developing irreversible end-stage cardiogenic shock. As a
      prehospital care provider, you must be able to ensure the pre-shock patient has
      adequate oxygenation of the myocardium and can be effectively treated before it
      is too late.

PMID- 15481661
TI  - Prehospital cardiac care Cuban style.
AB  - The Cuban national Integrated Medical Emergeny System or "Sistema Integrado de
      Urgencias Medicas" (SIUM) was formed in 1997. In 1998, the SIUM began an active
      out-of-hospital thrombolysis program using Heberkinasa, the only streptokinase
      obtained through recombinant DNA techniques, produced by the Cuban Center for
      Genetic Engineering and Biotechnology. An active community training program has
      also been implemented, standardizing training for the almost 20,000 members of
      the national emergency medical services.

PMID- 15481662
TI  - Computer-based training. Understanding the elements of good instructional design.

PMID- 15481663
TI  - EMS education on a shoestring.

PMID- 15481664
TI  - Will cheating kill EMS online education.

PMID- 15481665
TI  - The preceptor-student relationship: are you teaching students what they need to
      know?

PMID- 15481666
TI  - New York City's public safety communications: three years after 9/11.

PMID- 15481667
TI  - Failing to fund.

PMID- 15481668
TI  - Sweating the small stuff: understanding how corporate culture impacts customer
      services in EMS.

PMID- 15481669
TI  - Conflict causes and solutions.

PMID- 15481671
TI  - Pediatric paradox: heterogeneity in the birth cohort.
AB  - Comparisons of birth-weight-specific infant mortality indicate that low-birth
      weight African American infants have lower mortality than low-birth-weight
      European American infants despite higher infant mortality overall-the "pediatric
      paradox." One explanation is heterogeneity in birth weight. Analyses of African
      American and European American births suggest that birth cohorts consist of two
      heterogeneous subpopulations. One appears to account for normal births, whereas
      the other may consist of compromised births. Estimates of infant mortality
      indicate that the compromised subpopulation has higher overall mortality but
      lower birth-weight-specific mortality. We attribute lower birth-weight-specific
      infant mortality in the compromised subpopulation to higher rates of fetal loss.
      Compared to European American birth cohorts, African American birth cohorts have
      (1) higher birth-weight-specific mortality in the normal subpopulation, (2)
      larger compromised subpopulations, and (3) lower birth-weight-specific mortality
      in the compromised subpopulation. Consequently, the pediatric paradox is
      attributable to greater rates of compromised pregnancies and higher fetal losses
      among African Americans.

PMID- 15481670
TI  - Active surveillance for influenza infection in children; Stollery Children's
      Hospital, 2003-2004 season.

PMID- 15481672
TI  - Demographic analysis of the variation in the rates of multiple maternities in
      Sweden since 1751.
AB  - To elucidate the causes and mechanisms of twinning and higher multifetal
      maternities, we have taken advantage of the statistical sources of Sweden, where
      continuous statistics for the whole population are the oldest available. We found
      strong secular and regional fluctuations. The rates of multiple maternities were
      the highest during the last three decades of the 18th century, when the twinning
      rate was more than 17 per 1,000, the triplet rate was more than 3 per 10,000, and
      the quadruplet rate was almost 7 per 1 million maternities. During 1849-1873 the
      twinning rate in Sweden was 14.2 per 1,000, but this rate showed great regional
      differences, being 18.0 per 1,000 on the island of Gotland and 12.6 per 1,000 in
      the county of Alvsborg. During this period the twinning rate in the countryside
      in the county of Stockholm was 20.4, but in the city of Stockholm it was only
      14.1 per 1,000. In Sweden after the 1930s there was a marked decrease in the
      twinning rate, which by the 1960s had fallen to only about half of what it had
      been two centuries earlier. The corresponding reductions for triplet and
      quadruplet rates were about 75%. The aim of this paper was to study the temporal
      and regional variations in multiple maternities in Sweden from 1751 to 1960 based
      on demographic and some socioeconomic data for the counties. We confirmed our
      earlier studies that maternal age and parity cannot satisfactorily explain the
      secular and regional differences in the twinning rates. In contrast to studies in
      France (1901-1968), we found no unequivocal association between the twinning
      rates and the crude birth rates. The correlation coefficients between the
      twinning rate and the crude birth rate showed statistically significant regional
      and temporal variations. After eliminating the temporal trends, regional
      differences in the correlation coefficients remained. The twinning rates for the
      counties seem to converge toward a common low level, 10-12 per 1,000. The
      observed convergence toward relatively similar levels may be caused by the
      increased matrimonial migration distances and decreased endogamy of the citizens
      as a consequence of better communications. The increased urbanization and
      industrialization that started in the last decades of the 19th century broke up
      the old static agrarian isolates and caused Sweden, within 2-3 generations, to
      develop from a poor nation to one of the most prosperous in the world. A more
      urban and affluent lifestyle, a better diet, and increased stress and sedentary
      occupations may have reduced the physical capacity of mothers to carry gestations
      with multiple embryos or fetuses to completion.

PMID- 15481673
TI  - Opportunity for natural selection in a Basque population and its secular trend:
      evolutionary implications of epidemic mortality.
AB  - Analysis of the interaction between mortality patterns and opportunity for
      natural selection could help to elucidate potential evolutionary implications of
      epidemic mortality. In this paper secular trends are studied in relation to
      Crow's index (It) and its components of mortality (Im) and fertility (If), using
      parish records for family reconstitution in a Basque population. A principal
      components analysis (91% of the variance accounted for) showed marked
      quantitative and qualitative variations of Im and If depending on the stage of
      demographic transition of the population analyzed: In pretransitional societies
      the opportunity for natural selection is determined mainly by differential
      prereproductive mortality, whereas in posttransitional societies selection
      resulting from differential fertility plays a key role. The highest values for
      the mortality component (range 0.81-1.26) and for the relative contribution of
      Im, to It (range 47.1-57.2%) were observed in periods with a high incidence of
      infectious diseases and when the most severe mortality crises were detected (1830
      1859, 1860-1889, and 1890-1919). A differential incidence of epidemic mortality
      was also found at prereproductive ages (before 16 years) and at reproductive ages
      (16-45 years), which provides strong support for the idea of the long-term
      genetic consequences of mortality crises.

PMID- 15481674
TI  - Comparative analysis of dermatoglyphic traits in Hungarian and Gypsy populations.
AB  - We examined dermatoglyphic prints of children in 11 Hungarian and 5 Gypsy
      population samples (collected from 1,998 children). We compared Hungarian and
      Gypsy populations based on 22 finger and 24 palmar traits. In univariate
      comparisons the two ethnic groups differed significantly in half of the studied
      variables (9 finger and 14 palmar traits). We used several types of multivariate
      analyses of the studied traits to separate the population samples. Homogeneity
      analysis and discriminant analysis proved to be the most appropriate method to
      distinguish the populations, whereas a principal components analysis was less
      adequate. Multivariate analyses were conducted separately for both finger and
      palmar traits. Although the differences between the populations were more
      pronounced for palmar traits, in our study Hungarian and Gypsy populations showed
      the best separation when finger and palmar traits were combined for analysis,
      except in the principal components analysis. As expected, the Hungarian and Gypsy
      populations separated definitely in most statistical analyses; the main reason
      for this is the different origins of the two ethnic groups. The existence of the
      difference also shows that admixture between Hungarians and Gypsies has been
      small despite their living beside one another for several centuries.

PMID- 15481675
TI  - Evidence for a major gene influence on persistent developmental stuttering.
AB  - Stuttering is a complex developmental speech disorder of unknown etiology. There
      is a substantial aggregation of stuttering in families, suggesting a genetic
      component to the disorder. However, the exact mode of transmission is still
      unknown. An earlier study of 56 multigenerational pedigrees ascertained through
      single adult probands (38 males and 18 females) found that biological relatives
      of persistent developmental stutterers have an approximately 10-fold higher risk
      than in the general population; risk is higher for male relatives, and proband's
      sex does not affect recurrence and relative risks. In the present paper we
      conduct a complex segregation analysis of the same data, using the logistic
      regression model of the SAGE software. Based on the comparisons of model
      likelihoods, the Mendelian model was selected over all other nongenetic models
      and the general transmission model. This model was further refined into the most
      parsimonious model, which shows an autosomal dominant major gene effect
      influenced by two covariates: sex and affection status of parents. With this
      model applied to 47 informative multiplex pedigrees, a power calculation based on
      linkage simulation produced an average lod score of 6.8 for 10-cM density genome
      scan markers. These results give impetus for a genomewide linkage analysis of
      susceptibility to persistent developmental stuttering.

PMID- 15481676
TI  - Genetic structure and gene flow in Gran Chaco populations of Argentina: evidence
      from Y-chromosome markers.
AB  - The Gran Chaco region of central South America has been settled by humans for
      only the last 4,000-5,000 years. To investigate population structure and
      variation in this region's indigenous population, we scored males from tribes of
      the Argentinean part of the Gran Chaco (Pilaga, Wichi, and Toba, representing two
      major language groups, the Mataco and Guaycuru) for a number of Y-chromosome
      polymorphisms. The markers included eight microsatellites (DYS19, DYS390, DYS391,
      DYS392, DYS393, DYS437, DYS438, and DYS439) and the unique native American single
      nucleotide polymorphism, DYS199. Sixty males (77%) from the total sample carried
      the DYS199T chromosome, and these were the focus of the present analysis. Unlike
      most other native Americans, Gran Chaco males show a moderate level of diversity
      at the DYS19 locus but still less than that seen in non-native Americans. The FST
      value for Y-chromosome markers in Gran Chaco was 0.107, a value that is more than
      double that found for mtDNA haplogroups in the same tribes but is not
      particularly high compared with other Y-chromosome studies. Phylogenetic trees
      based on all eight microsatellites showed relatively poor correlation of the
      tribes with either geography or language, and this is possibly explained by their
      ecology. They are seasonal hunters living in small bands, and under such
      circumstances drift will be a powerful evolutionary force. An UPGMA tree based on
      five microsatellites (DYS19, DYS390, DYS391, DYS392, and DYS393), however, showed
      a more positive relationship, suggesting that DYS437, DYS438, and DYS439 may
      behave differently from the other microsatellites. No association was found
      between maternal and paternal lineage distributions. The time to the most recent
      common ancestor of the DYS199T chromosome is calculated to lie between 13,000 and
      26,000 years. This range is consistent with estimates from other Y-chromosome
      studies as well as with estimates from mtDNA and the archeology of the
      colonization of South America. We conclude that the male lineages present in the
      contemporary Gran Chaco population reflect the level of diversity found in South
      America and that the region's male founders did not carry a restricted gene pool.

PMID- 15481677
TI  - Determination of human caucasian mitochondrial DNA haplogroups by means of a
      hierarchical approach.
AB  - In this paper we propose a hierarchical approach that allows the screening of
      mitochondrial DNA (mtDNA) haplogroups in populations that have essentially West
      Eurasian mtDNA backgrounds but that could have some non-West Eurasian
      contributions. To develop and validate this scheme, we used data on 18 coding
      region polymorphisms (17 analyzed by RFLP analysis and 1 by sequencing) and
      sequences of hypervariable segment I (HVSI) of the mtDNA control region from the
      Azores Islands (Portugal) population. The proposed scheme allows the
      characterization of almost all West Eurasian and African major clusters by means
      of RFLPs. Furthermore, the scheme includes information on situations in which
      sequencing is pertinent to defining a particular haplogroup. The validity of the
      scheme is ensured by (1) using relatively stable polymorphic positions, (2)
      screening more than one position to define a specific haplogroup, and (3) typing
      confirmatory positions. Dubious samples can be resolved by sequencing. The
      robustness of this approach was assessed by sequencing all samples for HVSI,
      taking advantage of the previously established relationships between RFLPs and
      control region sequence polymorphisms. The use of this hierarchical approach
      avoids the screening of unnecessary control region polymorphisms and therefore
      results in a more rapid and cost-efficient screening than one in which all
      polymorphic positions are analyzed. Even if this approach leads to a lower level
      of phylogeographic resolution than the sequencing of all samples, it allows us to
      define population movements on a continental level and can be applied, unlike
      sequencing all samples, with a low cost in any laboratory.

PMID- 15481678
TI  - What is the incidence of cystic fibrosis in Italy? Data from the National
      Registry (1988-2001).
AB  - The mean incidence of cystic fibrosis (CF) among North Americans of European
      ancestry is 1 in 2,500. Studies carried out in different geographic areas report
      incidence values ranging from 1 in 1,800 to 1 in 8,500, suggesting that incidence
      has to be assessed specifically for any population. This paper represents the
      first attempt to evaluate the incidence of CF in Italy and its time-related
      changes following the discovery of the gene in 1989. Data recorded in the Italian
      National CF Registry for CF subjects born between 1988 and 2001 were evaluated.
      All CF patients (1,742) were diagnosed by 1 of 18 specialized CF centers and 7
      support services (1-3 in each region) according to the consensus statement on CF
      diagnosis. The average CF incidence in Italy was found to be 1 in 4,238, which is
      lower than the values reported elsewhere. The incidence remained nearly constant
      from 1988 to 2001, although the percentage of subjects screened for CF increased
      by 44%. Molecular analysis (available for more than 80% of the patients)
      indicated that the most common mutation (DF508) in Italy occurs in only 49% of CF
      chromosomes; the other mutations differ from region to region. These differences
      appeared to be mildly related to differences in reason for diagnosis and type of
      mutation. Italian registry data supply an incidence of CF lower than that
      reported for populations of European descent. Part of this difference is probably
      due to the higher allelic heterogeneity of the CFTR gene in Italy with respect to
      Northern Europe or the U.S. population of European descent.

PMID- 15481679
TI  - Y-chromosome haplotypes in azoospermic Israeli men.
AB  - Among azoospermic and severely oligozoospermic men, 7-15% present microdeletions
      of a region on the long arm of the Y chromosome that has been called AZF
      (azoospermia factor). Because these deletions present varying relative
      frequencies in different populations, we decided to ascertain whether their
      presence was correlated with specific Y-chromosome haplotypes. For that, we
      evaluated 51 infertile Israeli men, 9 of whom had microdeletions in AZF.
      Haplotypes were identified using a hierarchical system with eight biallelic DNA
      markers. We also checked for the presence of the deletion marker 50f2/C, which
      was absent in all seven patients with isolated AZFc deletion and also in the one
      patient with isolated AZFb deletion, suggesting that these microdeletions
      overlap. As expected, haplogroup J was the most common (47%), followed by equal
      frequencies of haplogroups Y* (xDE, J, K), P* (xR1a, R1b8), K* (xP), and E. In
      six patients with AZFc deficiencies of comparable size, three belonged to
      haplogroup J, two belonged to haplogroup P* (xR1a, R1b8), and one belonged to
      haplogroup R1a. Also, there were no significant differences in the haplotype
      frequencies between the groups with and without microdeletions. Thus we did not
      identify any association of a specific haplogroup with predisposition to de novo
      deletion of the AZF region in the Israeli population.

PMID- 15481680
TI  - Molecular basis of ESD*5 and ESD*7 and haplotype analysis with new polymorphisms
      in introns.
AB  - The two polymorphic alleles of esterase D (ESD), ESD*5 and ESD*7, are specific to
      Europeans and Asians, respectively. In this study the molecular basis was
      characterized: ESD*5, arising from ESD*1, has a G to A transition, resulting in
      Gly257(GGT) --> Asp(GAT); and ESD*7, originating from ESD*2, has an A to G
      transition, resulting in Asp231(GAT) --> Gly(GGT). Glycine is also involved in
      the common ESD*1/ESD*2 polymorphism [Gly190(GGA) --> Glu(GAA)]. Haplotype
      analysis using a few novel intragenic polymorphisms showed strong associations
      among polymorphic sites, suggesting that recombination has been less frequent in
      the human ESD gene, although it spans about 25 kb from exon 1 to exon 10. A
      marked difference was observed in the distribution of haplotype frequencies
      between Germans and Japanese.

PMID- 15481681
TI  - Making health predictions: can we really be so accurate?

PMID- 15481682
TI  - Physicians' perceptions of possibilities and obstacles prior to implementing a
      computerised drug prescribing support system.
AB  - Seeks to identify physicians' perceptions of possibilities and obstacles prior to
      implementing a computerised drug prescribing support system. Details a
      descriptive, qualitative study, with semi-structured individual interviews of 21
      physicians in the Accident and Emergency Department of South Stockholm General
      Hospital. Identifies four descriptive categories for possibilities and obstacles.
      Concludes that gaining access to patient drug history enables physicians to carry
      out work in a professional way--a need the computerised prescription support
      system was not developed for and thus cannot fulfil. Alerts and producer
      independent drug information are valuable in reducing workload. However,
      technical prerequisites form the base for a successful implementation. Time must
      be given to adapt to new ways of working.

PMID- 15481683
TI  - Optimising value and quality in general practice within the primary health care
      sector through relationship marketing: a conceptual framework.
AB  - Discusses the rationale of applying relationship marketing and service quality
      concepts within the primary health care sector. The use of relational strategies
      in general practice, by modelling the relationships between practitioners and
      patients from a marketing perspective, could potentially lead to sustained high
      quality service being provided, and to more efficient use of resources. This
      essentially conceptually focused paper addresses an area that has not yet been
      researched in detail, and furthers understanding of the relationships that
      facilitate exchange within general practice and service delivery in non-profit,
      resource-constrained conditions. Deeper understanding of the needs and
      expectations of patients and the way these can be delivered by general practice
      can only lead to improvements for all parties involved. The relationship
      marketing paradigm presents itself as a potentially exciting way of addressing
      issues associated with ensuring that the highest level of quality is delivered in
      this area of the UK National Health Service.

PMID- 15481684
TI  - The impact of hospital discharge on inappropriate hospital stay.
AB  - Appropriate hospital stay should be effective, efficient and tailored to patient
      needs. Previous studies have found that on average 20 per cent of hospital stay
      is inappropriate. Within obstetrics, inappropriate hospital stay consists mostly
      of delays in hospital discharge. The specific goals of this study were to reduce
      inappropriate hospital stay by fine-tuning patient logistics, increasing
      efficiency and providing more comfortable surroundings. New policies using strict
      discharge criteria were implemented. Total inappropriate hospital stay decreased
      from 13.3 to 7.2 per cent. The delay in discharge procedures halved. P-charts
      showed a decrease in inappropriate hospital stay, indicating the current process
      to be stable. Concludes that a significant reduction in inappropriate hospital
      stay was found following the implementation of innovative hospital discharge
      policies, indicating greater efficiency and accessibility of hospital services.

PMID- 15481685
TI  - A framework for the application of knowledge technology to the management of
      diseases.
AB  - Medical diagnosis and treatment constitute a network of interrelated processes.
      The conventional method of medical diagnosis and treatment of diseases involves a
      state space search of the medical knowledge of diseases and patient history,
      which could be combinatorially explosive. This paper presents a report on the
      experimental study of an intelligent, interactive, user-friendly, knowledge-based
      system which performs a stepwise analysis of a patient's complaints, filtering
      cognitive and emotional elements to be able to make inferences. It applies both
      forward and backward chaining in making inferences concerning the management of
      disease. A case study of the system is carried out using some tropical diseases.
      It is believed that the system will serve as a useful contribution towards
      tropical medical informatics.

PMID- 15481686
TI  - What's important in choosing a primary care physician: an analysis of consumer
      response.
AB  - Given the growth of health maintenance organizations and preferred physician
      organizations, the purpose of this study was to determine the salient factors
      considered when choosing a primary care physician. A list of informational items
      about physicians not normally included in provider directories but which were
      indicated by the literature to be important were included in the survey
      instrument. Employees of a major state university in a south-western state were
      surveyed. Results indicated that at the point of selection, the degree of patient
      satisfaction with the quality of care received and the accessibility of the
      physician were the two most relevant factors that impacted the choice of a
      physician. Other factors considered important included interpersonal skills and
      competence.

PMID- 15481687
TI  - Empathy: towards a conceptual framework for health professionals.
AB  - Effective provider-patient communication and the relationships that it supports
      are located at the centre of quality health-care delivery. The patient-centred
      approach is increasingly seen as an effective way to provide effective patient
      care, being more sensitive and responsive to the needs of the individual. Empathy
      has been identified as a core component of "patient-centredness" but definitions
      often lack conceptual clarity. This paper proposes to clarify the definition of
      empathy keeping the discussion true to Rogers' original definitions of the
      concept whilst integrating the work of other writers. A major thrust is the
      development of an innovative conceptual model of empathy which has the potential
      to both integrate previous research findings and provide a framework for future
      research and training. The model is based in social psychological conceptions of
      attitude.

PMID- 15481688
TI  - Measuring asthma patient satisfaction in Sweden using partial least squares.
AB  - Examines the relationships between different aspects involved in asthma
      treatment. Analyses each aspect's impact on overall patient satisfaction with
      asthma treatment. Also studies how outcome variables such as compliance with
      physician's recommendations, health-related quality of life and resource use are
      affected by the degree of patient satisfaction. The results refer to asthma
      patients as a group but not necessarily to each patient as an individual. The
      statistical technique applied for this analysis is partial least squares. Tests
      the suggested generic model on 599 respondents from a questionnaire survey. The
      structure of the suggested model is well supported by the data.

PMID- 15481689
TI  - An inspector calls... the practical reality of clinical governance.

PMID- 15481690
TI  - Quality assurance for clinical research: challenges in implementing research
      governance in UK hospitals.
AB  - The oversight of clinical research in the UK is currently in a state of flux.
      Discusses the quality assurance problems that have arisen in the management of
      research and the protection of the rights of human participants. Contrasts
      clinical governance and regulatory approaches to research quality assurance and
      performs a critical analysis of the Department of Health (England) Research
      Governance Framework (RGF) to see where it falls within the continuum. Highlights
      the implications for UK hospitals engaged in clinical research through the
      presentation of a case study in implementing the RGF. Concludes by suggesting the
      priority areas that need to be addressed and invites further debate regarding the
      merits of a clinical governance or regulatory approach to research quality
      assurance.

PMID- 15481691
TI  - Evaluating a health service taskforce.
AB  - A large number of taskforces and other quality improvement teams have been set up
      to achieve change in recent years, both in health and elsewhere, but there has
      been relatively little systematic evaluation of the benefits obtained. This paper
      discusses alternative methodologies and frameworks for assessing the value of
      taskforces and other quality improvement teams in the public sector and concludes
      that the Performance Prism, used in conjunction with the public sector scorecard,
      a variant of the balanced scorecard, is most appropriate. The paper then
      describes a case study on the evaluation of a UK health service taskforce using
      the recommended approach and reflects on its successes and limitations.

PMID- 15481692
TI  - Organisational culture: pursuing a theoretical foundation within the Finnish
      public oral health-care context.
AB  - At the moment, Finnish oral health care is undergoing many changes. Little
      attention has been paid to issues of organisational culture and communication in
      Finnish oral health care. Yet the question of culture is of primary importance
      for changes in an organisation and for planning and reconstructing the rational
      functioning of an organisation. The purpose of this paper is to examine Finnish
      public oral health care within a theoretical framework of organisational culture
      and to identify the various cultural traits that appear to characterise Finnish
      oral health care. Using a cultural point of view, we develop an orientation for
      understanding more profoundly and specifically the processes concerning the
      functioning and change of oral health care.

PMID- 15481693
TI  - A review of compliance studies in kidney transplanted adolescents.
AB  - Strong evidence exists that compliance with the treatment regimen is a major
      problem for many transplant patients. Noncompliance with the treatment regimen is
      particularly evident among kidney-transplanted adolescents. Research has not
      examined the adolescents' experience of living with a kidney transplant. Provides
      a review of the literature seeking to explain the causes of noncompliance in the
      population group. Although the studies referred to here provide insights into the
      situation, many lack reliability and validity because of methodological
      limitations. They also point to a gap in understanding the condition from the
      point of view of the adolescent. A more useful approach, therefore, is to use a
      qualitative research methodology. Such an approach has been shown to be useful in
      a study of diabetic adolescents, and offers promise for the greater understanding
      of kidney-transplanted adolescents and the impact the medical regimen has on
      them. With improved understanding comes the ability of health practitioners to
      better meet their needs in terms of improving the quality of their post-operative
      lives.

PMID- 15481694
TI  - Managerial process: the reflective practitioner.
AB  - The successful management journey is replete with moments of truth. Recognizing
      those moments and their significance for successful managerial practice is both a
      reflective and a conscious practice. This article, written by a successful
      pharmacist who now manages a busy public service hospital pharmacy documents his
      management journey from starting position as a drug store pharmacist to his
      present position in the public service. The paper uses managerial process theory
      as a critical tool to assess the author's own managerial style. Starting off as
      an autocratic manager with micro management tendencies, he has now developed a
      different style of management built on a basic philosophy about the value of
      people. He sees a need for managers to build a work environment that supports the
      efforts of employees. This style has not only made him a more effective people
      manager and motivator, but he argues it has also made him a better pharmacist.
      The author concludes by advocating the value of reflective practice, particularly
      for healthcare administrators as a means of balancing the technical demands of
      their disciplines with the ongoing requirements of managing people.

PMID- 15481695
TI  - Formulation and feedback: an illustration of two methods for improving access to
      effective therapies.
AB  - It is now recognised that therapists require career-long training in order to
      maintain and improve their expertise. However, training will fail to improve
      services to clients unless the work environment supports staff in its use.
      Although this "training transfer" problem is widely acknowledged, to the authors'
      knowledge the way that the work environment influences clients' access to
      effective therapies has not been subjected to a detailed and systematic
      formulation. Therefore, this small study illustrates a suitable formulation,
      based on the training received by a group of National Health Service (NHS) staff
      in "psychosocial interventions", and proposes its use as a "feedback fascia" to
      managers and others. To do this, structured interviews were held with a self
      selected sample of n = 20 therapists (mostly nurses) and all of their managers (n
      = 11) in one NHS Trust. The results indicated an impressive degree of training
      transfer. It is concluded that staff training can improve clients' access to
      effective treatments, but that significant organisational support for innovation
      is required. A feedback fascia can guide such support.

PMID- 15481696
TI  - Involving patients to improve service quality in primary care.
AB  - A sample of 92 UK patients volunteered to take part in focus groups to discuss
      what elements of local primary care provision were important to them. Issues
      raised were prioritised by the patients and then fashioned into 18 quality
      indicators which nine local practices were invited to assess themselves against.
      At the assessment meeting three months later over 40 changes in service provision
      were noted in the nine participating practices. A patient questionnaire carried
      out in each practice, however, indicated a tendency for practices to overestimate
      the services they felt they provided. Patients rated the experience of generating
      standards as very worthwhile and enjoyed being asked. Further research needs to
      be carried out to assess the effectiveness of this methodology in different
      settings.

PMID- 15481697
TI  - Autoinflammatory diseases: the hereditary periodic fever syndromes.
AB  - Human autoinflammatory diseases (HAIDs) are a heterogeneous group of genetically
      determined affections characterized by seemingly unprovoked inflammation, in the
      absence of autoimmune or infective causes. The hereditary periodic fever
      syndromes (HPFSs) are a HAID subset consisting of three main nosologic entities:
      familial Mediterranean fever (FMF), hyperimmunoglobulinemia D and periodic fever
      syndrome (HIDS), and tumor necrosis factor receptor superfamily 1A-associated
      periodic syndrome (TRAPS). FMF and HIDS are autosomal recessive diseases, while
      TRAPS is dominantly inherited. Although each HPFS presents genetic and phenotypic
      peculiarities, globally these affections share an intermittent expression, in
      form of acute attacks of fever variably associated with serosal, synovial and/or
      cutaneous inflammation, usually self-limiting. Amyloidosis is the most severe,
      life-threatening complication of FMF and TRAPS, whereas it has not been till now
      reported in HIDS. The HPFS molecular bases have been recently identified. In this
      paper, the most recent information on HPFSs is reviewed and summarized.

PMID- 15481698
TI  - Epidemiological aspects of human rotavirus infection in children hospitalized
      with acute gastroenteritis in an area of northern Italy.
AB  - Human rotavirus (HRV) is recognized as the most common cause of severe
      gastroenteritis in children under 5 years of age. Due to the lack of recent
      reports about the surveillance of HRV infection in Italy, in this study we
      assessed the prevalence rate of HRV infection on 1,340 stool samples belonging to
      1,264 pediatric patients hospitalized with acute gastroenteritis in the period
      January 2000--December 2002. The stool samples were submitted to virological
      investigations by electron microscopy (EM) and conventional cell culture, as well
      as from January 2002 by RT-PCR for norovirus detection. Reovirus-like particles
      observed by EM were identified by electropherotyping. Single HRV infections were
      detected in 302 cases (23.9%, ranging from 19.1% in 2000 to 30.2% in 2001). Mixed
      infections were observed in 28 cases in which HRV was found to be associated with
      adenovirus in 16 cases (1.3%), with picornavirus in 4 (0.3%), and with norovirus
      in 8 (2.1% of the 388 cases examined in 2002). The 3 major epidemic periods of
      HRV infections were March--May 2000 (66 cases), December 2000--May 2001 (128
      cases) and September 2001--April 2002 (105 cases) with peaks in March, January
      and March, and January, respectively. In the periods of major incidence, single
      HRV infection accounted even for 52.5% of the gastroenteritis cases monthly
      examined. According to age distribution, 68.9% (208 cases) of HRV infected
      children was under 4 years (69.6%: 230/330 cases, including mixed infections) and
      16.9% (51 cases) was in the 5-12-year age-group. The epidemiological aspects of
      HRV infection, also compared to other enteric virus infections, will contribute
      to assess the magnitude of the problem of HRV in different settings and to devise
      strategies for intervention.

PMID- 15481699
TI  - Cardiovascular and respiratory status in mechanically ventilated asphyxiated term
      infants: comparison between hypothermic and control group.
AB  - OBJECTIVE: To evaluate cardiorespiratory changes in hypothermic asphyxiated
      ventilated infants compared with controls. STUDY DESIGN: Retrospective chart
      analysis with historical controls. Cardiorespiratory status of 10 asphyxiated
      newborns in hypothermia (H) (32 degrees-34 degrees C) (H group) was compared with
      that one of 11 asphyxiated newborns [control group, (C group)]. RESULTS: 3/10
      patients in H group needed an increased mean tidal volume (from 5.8 to 8 ml/Kg)
      during hypothermia when temperature reached a value of 32 degrees C, to maintain
      adequate gas exchange. Length of mechanical ventilation was similar in the two
      groups (H=5.4+/-4.4 vs C=2.8+/-2.7 days, p=ns). Heart rate, similar at the
      baseline (H group: 129+/-11 beats/min; C group: 129+/-12 beats/min), dropped to
      an average of 102+/-10 beats/min (p<0.05) during cooling in H group, while it
      remained stable in C group. Mean arterial blood pressure, comparable at birth,
      increased by a median of 8 mmHg during hypothermia (p=ns). CONCLUSIONS:
      Hypothermia induces mild changes in cardiovascular status and in lung mechanics.

PMID- 15481700
TI  - The incidence of thyroid carcinoma in multinodular goiter: retrospective
      analysis.
AB  - Thyroid carcinoma (TC) is a relatively rare tumour, but it represents the most
      frequent form of cancer of the endocrine glands. Epidemiologically ascertained
      risk factors are ionising radiation, the presence of thyroid adenoma and
      multinodular goiter (MNG). Multinodularity of goiter should no longer be
      considered an indicator of probable benign disease. A retrospective analysis was
      performed on patients operated of MNG at the Unit of Otolaryngology, Sanremo
      Hospital (Italy) from January 1st 1995 to December 31st 2002, in order to
      establish the incidence of carcinoma. The results of this retrospective study,
      demonstrate that in 13.7% of the patients operated for goiter, the presence of a
      carcinoma was noticed in the definitive histopathologic examination. Such
      incidence percentage of MNG is in accordance with the data reported in published
      reports. Thus, the authors conclude that the risk of malignancy in MNG has not to
      be underestimated, and that a dominant nodule in MNG should be valued as if it
      were a solitary nodule in an otherwise normal gland.

PMID- 15481701
TI  - Role of camping in the treatment of childhood obesity.
AB  - Obesity is constantly increasing among children. Since treatment for obesity on
      outpatient bases often fails, we evaluated whether camps may help to improve
      eating habits. Forty-one children, 21 males and 20 females (BMI > 97 degrees
      percentile, weight excess > 30%, Tanner stage I) agreed to participate to a 8 day
      camp. After 1-year follow-up, measurements carried out by plicometry,
      bioelectrical impedance, metabolic and hormonal evaluations, showed a significant
      reduction of skinfolds, as well as glycemic and insulinemic response to the oral
      glucose tolerance test. These results suggest that camps may help to improve
      nutritional and physical education and psychological outcome of obese children.

PMID- 15481702
TI  - Effective clinical outcome of a mandibular distraction device using three
      dimensional CT with volume rendering in Pierre-Robin sequence.
AB  - Computed Tomography (CT) with three-dimensional reconstructions was studied in
      cranio-facial deformities. The pre-operative and follow-up study of cranio-facial
      deformities can be performed with spiral CT. With this modality quantitative
      information can be provided in order to measure the entity of airway obstruction
      and the result of procedure affecting bone structures.

PMID- 15481703
TI  - "Late" regressions of metastases from renal cancer after a period of disease
      progression continuing the same intermittent low dose immunotherapy regimen.
AB  - We here describe two patients with metastatic renal cell cancer (mRCC) treated
      with immunotherapy in whom the metastases completely regressed after a period of
      progressive disease. The treatment schedule was based on repeated cycles of low
      dose recombinant interleukin-2 and recombinant interferon-alpha, and was never
      changed during the course of the disease. The first patient received
      immunotherapy because of multiple bilateral lung metastases. Progressive disease,
      with mediastinal lymph node involvement and an increased number of lung
      metastases, was observed after 30 months of regularly repeated therapy; complete
      regression was achieved after 60 months of immunotherapy (after 16 immunotherapy
      cycles). The second patient began immunotherapy because of three small lung
      metastases. Disease progression was observed after three cycles, but complete
      regression was obtained about 16 months after the start of immunotherapy (after 5
      immunotherapy cycles). Long-term low-dose immunotherapy may bring about an
      effective anti-tumour response even late in the course of the disease and after
      an initial disease progression.

PMID- 15481704
TI  - Spontaneous renal allograft rupture without acute rejection.
AB  - Renal allograft rupture (RAR) is a rare but potentially serious complication in
      the transplanted recipients. The most common cause is acute rejection. We report
      four cases (0.5%) of RAR occurred in a series of 778 consecutive kidney
      transplantations due to severe acute tubular necrosis and renal vein thrombosis
      with no evidence of acute rejection. Transplant nephrectomy was performed in
      three patients, whereas graft repair was achieved in one patient. These data
      suggest that RAR may be associated with renal vein thrombosis or severe acute
      tubular necrosis in absence of acute rejection. Frequently nephrectomy is
      necessary, but conservative surgical treatment should be attempted to preserve
      the allograft in selected cases.

PMID- 15481706
TI  - Rathke cleft cysts.

PMID- 15481705
TI  - Radioiodine and thyroid carcinoma: KI prophylaxis in children.
AB  - The Chernobyl disaster was followed by a large increase in the incidence of
      thyroid carcinoma in children. It has been proved that KI prophylaxis may prevent
      such a heavy consequence. Italy has no more nuclear power plants in activity but
      is surrounded by the several ones of the neighbouring countries; moreover,
      relevant amounts of nuclear material are still present in the territory.
      Therefore a nuclear risk is present in Italy as well as in other close countries
      and a KI prophylaxis should be organized for our children, at least for those
      living within 200 miles from a possible source of radioiodine pollution.
      Guidelines concerning KI prophylaxis exist and are internationally shared in
      their general outlines. Guidelines we recommend for italian children are
      summarized in part II ("theory"). However, to be timely and effective, KI
      prophylaxis must be organized long before the nuclear alarm, and the coordination
      of its several steps needs to be checked through a mock trial. We suggest a model
      of organization and describe the practical aspects of carrying out a KI
      prophylaxis for 82.000 subjects aged 0-18 years living in the Province of Parma
      (Progetto Sperimentale Parma, PSP). The main goal of PSP is to offer a controlled
      and reliable model of KI prophylaxis,which could be applied in any other area
      (previous local adjustement), whenever the central or regional Authorities will
      consider it necessary or desirable.

PMID- 15481707
TI  - Radiosurgery and radiotherapy.

PMID- 15481708
TI  - Deep brain stimulation and psychosurgery.

PMID- 15481709
TI  - Surgery for Rathke cleft cysts: technical considerations and outcomes.
AB  - OBJECT: The aim of this study was to identify the optimal surgical goals and
      techniques for managing symptomatic Rathke cleft cysts (RCCs). METHODS: The
      authors conducted a retrospective study of 62 consecutive patients who had
      undergone surgery for RCCs. Postoperative follow up was a mean of 28 months.
      Fifty-six patients underwent transsphenoidal cyst decompression and biopsy
      procedures, and six underwent cyst wall resection. Postoperatively, symptoms
      improved in 91% of patients with headaches and 92% of patients with visual
      deficits. Decompression and biopsy were associated with a 10% incidence of new
      anterior pituitary hormone deficiencies and a 6% incidence of new permanent
      diabetes insipidus; the incidence of new hormone deficiencies was significantly
      higher in the few patients who had undergone cyst wall resection. The incidence
      of relapse, defined as cyst regrowth with either recurrent symptoms or chiasmal
      compression, was 16%. Resection of the cyst wall was associated with a trend
      toward a decreased risk of relapse. Sellar packing, sellar floor reconstruction,
      and irrigation with absolute ethanol did not affect the likelihood of relapse.
      Squamous metaplasia and inflammation increased the risk of relapse. Residual cyst
      demonstrated on postoperative magnetic resonance imaging was associated with an
      increased risk of subsequent asymptomatic cyst regrowth. Seven patients (11%)
      underwent repeated operation with symptomatic improvement and minimal morbidity;
      only one patient relapsed following a second surgery. CONCLUSIONS: Decompression
      and biopsy procedures in the treatment of RCCs lead to improvement in signs and
      symptoms, with low morbidity rates. Repeated operations will be required in as
      many as 16% of patients but are also associated with symptomatic improvement, low
      morbidity, and durable remission. Decompression and biopsy may represent the
      optimal surgical management of RCC.

PMID- 15481710
TI  - Radiosurgery and radiotherapy: observations and clarifications.
AB  - OBJECT: Radiosurgery and radiation therapy represent important but unique
      treatment paradigms for patients with certain neoplasms, vascular lesions, or
      functional disorders. The authors discuss their differences. METHODS: Reviewing
      the authors' experiences shows how the roles of these approaches vary just as
      their techniques differ. The distinct differences include the method of target
      localization (intraoperative compared with pretreatment) and irradiation (focused
      compared with wide-field), their radiobiology (effects of a single high-dose
      compared with multiple fractions), the physicians and other health personnel
      involved in the conduct of these procedures (surgical team compared with
      radiation team), and the expectations that follow treatment. During the last
      decade, considerable confusion has grown regarding nomenclature, requisite
      physician training, and the roles of the physician and surgeon. Ten years ago,
      two task forces on radiosurgery were created by national organizations in
      neurosurgery and radiation oncology to address these issues of procedural conduct
      and quality-assurance requirements. At the present time these guidelines are
      widely ignored. Currently, many patients, payers, and regulatory agencies are
      bewildered. What are the differences among stereotactic radiosurgery,
      fractionated radiation therapy, and stereotactic radiation therapy? Radiosurgery
      is to radiation therapy as microsurgery is to "microtherapy." CONCLUSIONS: In
      this report the authors discuss terminology, training, and physician roles in
      this expanding field.

PMID- 15481711
TI  - Leksell Gamma Knife coordinate setting slippage: how often, how much?
AB  - OBJECT: The aim of this study was to determine the incidence and magnitude of
      coordinate setting slippage during gamma knife surgery (GKS). METHODS: Thirty-six
      consecutive patients undergoing GKS with a Leksell unit between June and December
      2000 had their coordinates (right and left x-, y-, and z-coordinates; 1548
      coordinates; 258 isocenters) and gamma angles checked after the delivery of
      treatment to each isocenter to determine whether the coordinate settings had
      slipped and, if so, which settings and the magnitude of the slippage.
      CONCLUSIONS: Coordinate setting slippage during GKS with a Leksell unit does
      occur but is rare. The magnitude of such slippage is typically within the error
      of the stereotactic system and coordinate reading. The authors noted that
      coordinate setting slippage is significantly correlated with patient weight.

PMID- 15481712
TI  - The effect of nimodipine on cerebral oxygenation in patients with poor-grade
      subarachnoid hemorrhage.
AB  - OBJECT: Nimodipine has been shown to improve neurological outcome after
      subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is
      uncertain. In addition, adverse systemic effects such as hypotension have been
      described. The authors investigated the effect of nimodipine on brain tissue PO2.
      METHODS: Patients in whom Hunt and Hess Grade IV or V SAH had occurred who
      underwent aneurysm occlusion and had stable blood pressure were prospectively
      evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was
      delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained
      from 11 patients and measurements of brain tissue PO2, intracranial pressure
      (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP)
      were recorded every 15 minutes. Nimodipine resulted in a significant reduction in
      brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before
      nimodipine administration was 38.4+/-10.9 mm Hg. The baseline MABP and CPP were
      90+/-20 and 84+/-19 mm Hg, respectively. The greatest reduction in brain tissue
      PO2 occurred 15 minutes after administration, when the mean pressure was 26.9+/
      7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5+/-7.7 mm Hg
      [p < 0.05]) and at 60 minutes (29.7+/-11.1 mm Hg [p < 0.05]) after nimodipine
      administration but returned to baseline levels 2 hours later. In the seven
      patients in whom brain tissue PO2 decreased, other physiological variables such
      as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not
      demonstrate any association with the nimodipine-induced reduction in PO2. In four
      patients PO2 remained stable and none of these patients had a significant
      increase in brain tissue PO2. CONCLUSIONS: Although nimodipine use is associated
      with improved outcome following SAH, in some patients it can temporarily reduce
      brain tissue PO2.

PMID- 15481713
TI  - Early surgery-related complications after aneurysm clip placement: an analysis of
      causes and patient outcomes.
AB  - OBJECT: Most reports of series on ruptured intracranial aneurysms contain
      information on select intraoperative complications. An understanding of all
      surgical complications, however, may guide us toward improved surgical procedures
      and enrich discussions concerning alternative management strategies, such as
      endovascular treatment, which are not exempt from complications and aneurysm
      recurrence. METHODS: The study consists of a retrospective review of the charts,
      images, and notes from follow-up visits of 143 consecutive patients with
      subarachnoid hemorrhage (SAH) who were surgically treated during a 3-year period
      by one neurosurgeon. A surgical complication was determined based on findings of
      a clinical and/or radiological study in the absence of confounding factors such
      as the initial SAH ictus, vasospasm, hydrocephalus, and septic status. Functional
      outcome was assessed between 2 and 3 months post-SAH by using the Glasgow Outcome
      Scale (GOS). A procedure-related surgical complication was diagnosed in 29
      (20.3%) of 143 patients studied. A brain tissue injury, including cerebral edema
      and hemorrhagic contusions, was diagnosed in 6.3% of patients, an unpredicted
      residual aneurysm neck in 5.3% of patients, and a cranial nerve deficit in 2.8%
      of patients. Functional outcome was good in 22 (75.9%) of the 29 patients with
      surgical complications. Death due to a surgical complication occurred in one
      (0.7%) of 143 patients. CONCLUSIONS: Surgical complications are more prevalent
      than previously thought. They may have been overlooked previously because of the
      high percentage of good functional outcomes and low mortality rates in this
      group. The identification of surgical complications may encourage the search for
      solutions to improve surgical treatment of aneurysmal SAH.

PMID- 15481714
TI  - Postoperative evaluation of microsurgical resection for cavernous malformations
      of the brainstem.
AB  - OBJECT: The aim of this study was to propose criteria to determine whether
      complete resection of cavernous malformations in the brainstem had been achieved.
      METHODS: The authors retrospectively analyzed data in 10 patients harboring a
      single cavernous malformation who had presented with hemorrhagic symptoms and had
      been followed up for longer than 2 years postsurgery. The study population
      consisted of five male and five female patients ranging in age from 13 to 57
      years (mean 36.8 years). When preoperative magnetic resonance (MR) images
      demonstrated the lesion as a homogeneous hyperintense mass, the surgery was
      defined as complete or incomplete based on intraoperative findings. When
      preoperative MR images revealed other findings, complete resection was determined
      according to whether postoperative MR imaging results demonstrated lesions
      distinct from the peripheral hemosiderin rim. Among the 13 operations in this
      series, nine resulted in complete resection and were associated with no
      postoperative clinical relapse of hemorrhage, whereas four operations resulted in
      incomplete resection and were correlated with postoperative recurrent hemorrhage.
      The seven patients in whom the outcome of the initial operation was complete
      demonstrated good neurological recovery in the long-term follow-up period,
      whereas the three patients in whom the outcome of the initial surgery was judged
      to be incomplete showed inadequate neurological recovery due to recurrent
      hemorrhage. CONCLUSIONS: The criteria proposed in this study to evaluate surgical
      treatment may be a reliable means of predicting the recurrence of hemorrhage
      postoperatively.

PMID- 15481715
TI  - Mesial temporal lobe epilepsy: a proton magnetic resonance spectroscopy study and
      a histopathological analysis.
AB  - OBJECT: Proton magnetic resonance (MR) spectroscopy imaging of the ratio of N
      acetylaspartate (NAA) to creatine (Cr) has proved efficacious as a localizing
      tool in demonstrating the metabolic changes associated with temporal lobe
      epilepsy. To analyze the significance of these MR spectroscopy findings further,
      the authors explored the relationship between regional alterations in the NAA/Cr
      ratio in hippocampi measured preoperatively and histopathological findings in
      hippocampi resected in patients with intractable mesial temporal lobe epilepsy
      (MTLE). METHODS: Twelve patients in whom the diagnosis of MTLE had been made and
      12 healthy volunteers with no known history of neurological disease underwent
      high-resolution 1H MR spectroscopy imaging of NAA and Cr (0.64 cm3 nominal voxel
      resolution) in five voxels spanning the anteroposterior length of the
      hippocampus. The authors correlated the NAA/Cr ratio with neuropathological
      findings in resected hippocampi, specifically glial fibrillary acidic protein
      (GFAP) immunoreactivity and pyramidal neuronal loss. A linear regression analysis
      of the ipsilateral NAA/Cr ratio revealed a statistically significant relation to
      the extent of hippocampal neuronal loss in only the CA2 sector (correlation
      coefficient [r] = -0.66, p < 0.03). The ipsilateral NAA/Cr ratio displayed
      significant regressions with GFAP immunoreactivity from all the CA sectors (r
      values ranged from -0.69 and p < 0.01 for the CA4 sector to -0.88 and p < 0.001
      for the CA2 sector) except for the CA1. The extent of neuronal cell loss in every
      hippocampal subfield (r = 0.71-0.74, p < 0.007), except the CA2 (p = 0.08),
      correlated to the extent of neuronal cell loss in the dentate gyrus. There was no
      significant relationship between the duration or frequency of seizures and the
      mean ipsilateral NAA/Cr ratio; however, the mean density of GFAP-immunopositive
      cells correlated with seizure frequency (p < 0.03). CONCLUSIONS: The NAA/Cr ratio
      may not measure the full extent of hippocampal neuronal cell loss. The
      significant association of the NAA/Cr ratio with the GFAP immunoreactivity of
      most CA sectors indicates that the NAA/Cr ratio may provide a more accurate
      measurement of recent neuronal injury caused by epileptic activity. The coupling
      between neuronal impairment and astroglial GFAP expression may indicate the close
      association between neuronal and glial dysfunction in patients with epilepsy.

PMID- 15481716
TI  - Craniotomy for supratentorial brain tumors: risk factors for brain swelling after
      opening the dura mater.
AB  - OBJECT: Cerebral swelling often occurs during craniotomy for cerebral tumors. The
      primary aim in this study was to determine risk factors (intracranial pressure
      [ICP], patient characteristics, histopathological features, neuroimaging
      characteristics, anesthetic regimen, and perioperative physiological data)
      predictive of brain swelling through the dural opening. As a secondary aim the
      authors attempted to define subdural ICP thresholds associated with brain
      swelling. METHODS: The study population consisted of 692 patients (mean age 50+/
      15 years) scheduled for elective craniotomy for supratentorial brain tumors.
      Brain swelling through the dural opening was estimated according to a four-point
      scale. The patients were dichotomized as those without cerebral swelling (that
      is, brain below the dura mater [59 patients] or brain at the level of the dura
      mater [386 patients]) and those with cerebral swelling (that is, moderate brain
      swelling [205 patients] or pronounced brain swelling [42 patients]). Logistic
      regression analysis was used to identify subdural ICP (odds ratio [OR] 1.9, 95%
      confidence interval [CI] 1.72-2.1, p < 0.0001), midline shift (OR 1.06, 95% CI
      1.02-1.11, p = 0.008), a diagnosis of glioblastoma multiforme (OR 2.1, 95% CI
      1.01-4.3, p = 0.047), and metastasis (OR 2.9, 95% CI 1.3-6.9, p = 0.01) as
      independent risk factors of intraoperative brain swelling. Thresholds for ICP
      associated with brain swelling were defined as follows: at an ICP less than 5 mm
      Hg, brain swelling rarely occurred (5% probability); at an ICP greater than 13 mm
      Hg, brain swelling occurred with 95% probability; and at an ICP greater than 26
      mm Hg, severe brain swelling occurred with 95% probability. CONCLUSIONS: Subdural
      ICP is the strongest predictor of intraoperative brain swelling. It is possible
      to define thresholds of cerebral swelling and the authors recommend subdural ICP
      measurement as a tool to initiate preventive measures to reduce ICP before
      opening the dura mater.

PMID- 15481717
TI  - Cerebrospinal fluid shunt placement for pseudotumor cerebri-associated
      intractable headache: predictors of treatment response and an analysis of long
      term outcomes.
AB  - OBJECT: Cerebrospinal fluid (CSF) shunts effectively reverse symptoms of
      pseudotumor cerebri postoperatively, but long-term outcome has not been
      investigated. Lumboperitoneal (LP) shunts are the mainstay of CSF shunts for
      pseudotumor cerebri; however, image-guided stereotaxy and neuroendoscopy now
      allow effective placement of a ventricular catheter without causing
      ventriculomegaly in these cases. To date it remains unknown if CSF shunts provide
      long-term relief from pseudotumor cerebri and whether a ventricular shunt is
      better than an LP shunt. The authors investigated these possibilities. METHODS:
      The authors reviewed the records of all shunt placement procedures that were
      performed for intractable headache due to pseudotumor cerebri at one institution
      between 1973 and 2003. Using proportional hazards regression analysis, predictors
      of treatment failure (continued headache despite a properly functioning shunt)
      were assessed, and shunt revision and complication rates were compared between LP
      and ventricular (ventriculoperitoneal [VP] or ventriculoatrial [VAT]) shunts.
      Forty-two patients underwent 115 shunt placement procedures: 79 in which an LP
      shunt was used and 36 in which a VP or VAT shunt was used. Forty patients (95%)
      experienced a significant improvement in their headaches immediately after the
      shunt was inserted. Severe headache recurred despite a properly functioning shunt
      in eight (19%) and 20 (48%) patients by 12 and 36 months, respectively, after the
      initial shunt placement surgery. Seventeen patients without papilledema and 19
      patients in whom preoperative symptoms had occurred for longer than 2 years
      experienced recurrent headache, making patients with papilledema or long-term
      symptoms fivefold (relative risk [RR] 5.2, 95% confidence interval [CI] 1.5-17.8;
      p < 0.01) or 2.5-fold (RR 2.51, 95% CI 1.01-9.39; p = 0.05) more likely to
      experience headache recurrence, respectively. In contrast to VP or VAT shunts, LP
      shunts were associated with a 2.5-fold increased risk of shunt revision (RR 2.5,
      95% CI 1.5-4.3; p < 0.001) due to a threefold increased risk of shunt obstruction
      (RR 3, 95% CI 1.5-5.7; p < 0.005), but there were similar risks between the two
      types of shunts for overdrainage (RR 2.3, 95% CI 0.8-7.9; p = 0.22), distal
      catheter migration (RR 2.1, 95% CI 0.3-19.3; p = 0.55), and shunt infection (RR
      1.3, 95% CI 0.3-13.2; p = 0.75). CONCLUSIONS: Based on their 30-year experience
      in the treatment of these patients, the authors found that CSF shunts were
      extremely effective in the acute treatment of pseudotumor cerebri-associated
      intractable headache, providing long-term relief in the majority of patients.
      Lack of papilledema and long-standing symptoms were risk factors for treatment
      failure. The use of ventricular shunts for pseudotumor cerebri was associated
      with a lower risk of shunt obstruction and revision than the use of LP shunts.
      Using ventricular shunts in patients with papilledema or symptoms lasting less
      than 2 years should be considered for those with pseudotumor cerebri-associated
      intractable headache.

PMID- 15481718
TI  - Acute alterations in microvascular basal lamina after subarachnoid hemorrhage.
AB  - OBJECT: Aneurysmal subarachnoid hemorrhage (SAH) causes acute and delayed
      ischemic brain injuries. The mechanisms of acute ischemic injury following SAH
      are poorly understood, although an acute increase in microvascular permeability
      has been noted. The integrity of cerebral microvessels is maintained in part by
      components of basal lamina: collagen IV, elastin, lamina, and so forth.
      Destruction of basal lamina components by collagenases and matrix
      metalloproteinases (MMPs), especially MMP-9, has been known to occur in other
      ischemic models. The authors assessed the integrity of cerebral microvasculature
      after acute SAH by examining collagen IV and MMP-9 levels and collagenase
      activity in the microvessels. METHODS: Subarachnoid hemorrhage was induced in
      rats through endovascular perforation of the intracranial bifurcation of the
      internal carotid artery. Animals were killed 10 minutes to 48 hours after SAH or
      sham operation (time-matched controls). Levels of collagen IV and MMP-9 were
      studied in the microvasculature by performing immunoperoxidase and
      immunofluorescence staining, and collagenase activity was assessed by in situ
      zymography. Little change occurred in collagen IV and MMP-9 immunostaining or
      collagenase activity at 10 minutes or 1 hour after SAH. Starting 3 hours after
      SAH, collagen IV immunostaining was reduced or eliminated along segments of
      microvessels whereas MMP-9 staining was segmentally increased. These effects
      reached a maximum at 6 hours and returned toward those values in sham-operated
      controls at 48 hours. CONCLUSIONS: Results of this study demonstrated an acute
      loss of collagen IV from the cerebral microvasculature after SAH and indicated
      that MMP-9 contributes to this event. The loss of collagen IV might contribute to
      the known failure of the blood-brain barrier after SAH.

PMID- 15481719
TI  - Alpha2-adrenergic receptor subtype specificity of intrathecally administered
      tizanidine used for analgesia for neuropathic pain.
AB  - OBJECT: Intrathecally administered alpha2-adrenergic receptor subtype-specific
      antagonists were used to determine which alpha2-adrenergic receptor subtype
      mediates the analgesic effect of intrathecally administered tizanidine in a
      chronic constriction injury (CCI) rat model of neuropathic pain. METHODS: Seven
      days after CCI and intrathecal catheter surgeries had been performed in Sprague
      Dawley rats, baseline neuropathic pain tests including cold-floor ambulation and
      paw pinch were performed. Either the dimethyl sulfoxide vehicle (seven rats) or
      one of the antagonists--5, 23, or 46 microg yohimbine (22 rats); 5, 25, 50, or
      100 microg prazosin (25 rats); or 5, 45, or 90 microg WB4101 (11 rats)--were
      intrathecally administered to the animals, followed in 30 minutes by 50 microg
      intrathecally administered tizanidine. The neuropathic pain tests were repeated
      30 minutes later. The resulting profile showed a descending order of antagonist
      efficacy for yohimbine, prazosin, and WB4101 for the cold-floor ambulation test
      and for the paw-pinch test of the affected paw. As expected given tizanidine's
      lack of analgesic effect on the contralateral, normal paw, there were no effects
      of antagonists on contralateral paw responses. The results of the paw-pinch test
      on the affected side were compared with binding data cited in the existing
      literature for the three different alpha2-adrenergic receptor subtypes (alpha2A,
      alpha2B, and alpha2C) with yohimbine, prazosin, and WB4101. The antagonist
      response profile for the paw-pinch test of the affected paw most closely
      approximated the alpha2B receptor binding profile. CONCLUSIONS: The antagonist
      profile from the current study is most consistent with the theory that the
      alpha2B-adrenergic receptor subtype mediates the analgesic effect of
      intrathecally administered tizanidine on CCI-associated neuropathic pain.

PMID- 15481720
TI  - Reduction of neural adhesions by biodegradable autocrosslinked hyaluronic acid
      gel after injury of peripheral nerves: an experimental study.
AB  - OBJECT: Adhesion formation is a serious problem in peripheral nerve surgery,
      frequently causing dysfunction and pain. The authors aimed to develop an
      objective biomechanical method of quantifying nerve adhesions and to use this
      technique for the evaluation of the efficacy of an autocrosslinked hyaluronic
      acid (HA) gel as an antiadhesion therapy. METHODS: Thirty-three female Wistar
      rats underwent dissection, crush injury, or transection plus repair of the
      sciatic nerve. The nerves were or were not treated with the HA gel. Six weeks
      after surgery, the adhesions formed were assessed by measuring the peak force
      required to break the adhesions over a standardized area. Results of
      biomechanical measurements demonstrated that the peak force significantly
      increased as the severity of the injury increased. After using the HA gel to
      treat the nerve, the peak force was significantly reduced in rats with any of the
      three types of injuries; peak force decreased by 26% in the animals in the
      dissection group, 29% in the crush injury group, and 38% in the transection and
      repair group, compared with the untreated animals. CONCLUSIONS: The biomechanical
      method described is an objective, quantitative technique for the assessment of
      nerve adherence to surrounding tissue. It will be a valuable tool in future
      studies on antiadhesion therapies. Furthermore, HA gel significantly reduces
      nerve adhesions after different types of nerve injuries.

PMID- 15481721
TI  - Mismatch repair protein hMSH2 in primary drug resistance in in vitro human
      malignant gliomas.
AB  - OBJECT: The mismatch repair (MMR) system has previously been implicated in
      acquired chemoresistance in malignant gliomas in humans. Its impact on the
      primary chemoresistance in glioblastoma multiforme (GBM) has not been determined
      in detail, however. METHODS: The authors investigated the expression of both the
      MMR genes (hMSH2, hMLH1, hPMS1, hPMS2, and hMSH6) at the transcriptional level
      through reverse transcription-polymerase chain reaction and the hMSH2 protein
      through Western blot and immunohistochemical analysis of tumor tissue and primary
      cell cultures of 25 in vitro human de novo GBMs without prior experimental
      treatment. Results of these analyses were compared with data on in vitro
      chemoresistance to nine drugs that are in general use in glioma therapy. All MMR
      genes were expressed in the GBMs, with no significant difference among the
      individual tumors except in one respect; that is, GBMs showed either relatively
      high levels or barely detectable levels of hMSH2 messenger (m)RNA and protein
      expression. All multiresistant tumors demonstrated high hMSH2 expression, and all
      but two of the sensitive tumors exhibited low hMSH2 mRNA levels. CONCLUSIONS:
      Analysis of the data indicates that functional alterations of the MMR system are
      involved in the primary drug resistance in in vitro human malignant gliomas.
      Analysis of hMSH2 expression might therefore predict therapeutic responses in
      humans with GBMs.

PMID- 15481722
TI  - Induction of the DNA repair gene O6-methylguanine-DNA methyltransferase by
      dexamethasone in glioblastomas.
AB  - OBJECT: The DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT)
      inhibits the cytotoxic effect of alkylating agents on tumor cells. The presence
      of two nonconsensus glucocorticoid-responsive elements in the human MGMT promoter
      region indicates the potential regulation of MGMT expression by glucocorticoid
      agents. This study was performed to elucidate whether dexamethasone affects the
      expression of MGMT in glioblastoma multiforme (GBM) cells, thereby limiting the
      benefit of chemotherapeutic alkylating agents. METHODS: Four GBM cell lines
      (A172, T98G, U138MG, and U87MG) were exposed to the alkylating agent 1-(4-amino-2
      methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU)
      with or without dexamethasone. The expression levels of MGMT were correlated with
      the cytotoxic effects of ACNU in GBM cells. In the presence of ACNU alone,
      dexamethasone alone, and the combination of both agents, messenger RNA expression
      of MGMT was induced to varying degrees with the highest increases seen in the
      later conditions. This dexamethasone-dependent induction of the MGMT gene was
      even observed in U87MG cells in which the promoter is methylated, although the
      absolute expression of MGMT mRNA was the lowest in that cell line. The induction
      of MGMT by dexamethasone was associated with an increased resistance of these
      cells to ACNU. CONCLUSIONS: These results indicate that dexamethasone-mediated
      upregulation of MGMT limits the efficiency of alkylating agents in the treatment
      of malignant gliomas.

PMID- 15481723
TI  - Optimal blood glucose levels while using insulin to minimize the size of
      infarction in focal cerebral ischemia.
AB  - OBJECT: Insulin has been shown to ameliorate cerebral necrosis in global and,
      more recently, in focal cerebral ischemia. The goal of this study was to
      determine the relationship between this neuroprotective effect and blood sugar
      levels in a rat model of focal ischemia. METHODS: Thirty-four rats were subjected
      to 80 minutes of transient middle cerebral artery occlusion at a mean arterial
      blood pressure of 60 mm Hg and a temperature of 37 degrees C. Insulin (3.5 IU/kg)
      was administered 1 hour before (12 rats) and 20 minutes after (12 rats) ischemia;
      10 animals served as controls. A quantitative histopathological study conducted
      after 1 week of survival showed that insulin was not beneficial in reducing the
      size of the infarction or selective neuronal necrosis in the penumbra when
      administered before or after ischemia. In addition to infarction, six animals
      from the insulin-treated groups had bilateral selective neuronal necrosis in the
      hippocampus or the neocortex. A nonlinear regression analysis in which glucose
      levels were compared with both cortical necrosis and total infarction yielded a U
      shaped curve with a nadir for cerebral necrosis that lay in the 6- to 7-mM blood
      glucose range. The increased brain damage induced by insulin occurred in animals
      with very low blood sugar values in the range of 2 to 3 mM. CONCLUSIONS: These
      results in rats indicate that if insulin is used following ischemia, blood
      glucose levels should be maintained at approximately 6 to 7 mM. From these data
      one can infer that hypoglycemia of less than 3 mM should be avoided in situations
      of focal cerebral ischemia in which insulin is used. Additional animal studies
      and clinical trials in humans are needed to study the effects of insulin on
      ischemia.

PMID- 15481724
TI  - Neuroprotective effect of peroxynitrite decomposition catalyst and poly(adenosine
      diphosphate-ribose) polymerase inhibitor alone and in combination in rats with
      focal cerebral ischemia.
AB  - OBJECT: The authors evaluated the neuroprotective effect of 5,10,15,20-tetrakis(N
      methyl-4'-pyridyl)porphyrinato-iron(III) (FeTMPyP), a peroxynitrite decomposition
      catalyst, and 1,5-isoquinolinediol (ISO), a poly(adenosine diphosphate [ADP]
      ribose) polymerase (PARP) inhibitor, alone and in combination in rats with focal
      cerebral ischemia induced by middle cerebral artery occlusion (MCAO). METHODS:
      Male Sprague-Dawley rats were subjected to 2 hours of MCAO followed by 22 hours
      of reperfusion. Cerebral infarction and neurological deficits were estimated
      after ischemia. Intraperitoneal injections of FeTMPyP (1 and 2 mg/kg) and ISO
      (0.05 and 0.1 mg/kg) were administered alone or in combination in ischemic
      animals. The PARP activity in vehicle- and drug-treated groups was estimated
      using anti-poly(ADP-ribose) antibody in immunofluorescence and immunoblotting
      studies. Two hours of MCAO and 22 hours of reperfusion produced significant
      cerebral infarction and neurological deficits. Treatment with FeTMPyP (1 and 2
      mg/kg) and ISO (0.05 and 0.1 mg/kg) produced a significant reduction in cerebral
      infarction and neurological deficits. Combination therapy (2 mg/kg FeTMPyP and
      0.1 mg/kg ISO) enhanced the inhibition of ischemic volume (77.81+/-0.86%)
      compared with monotherapies (FeTMPyP 54.07+/-5.6% and ISO 53.06+/-3.88%).
      Immunoblotting and immunofluorescence studies showed PARP activation after
      ischemia, which was reduced by drug treatment. CONCLUSIONS: Neuroprotection
      observed with FeTMPyP and ISO alone and in combination may be attributed to
      inhibition of the peroxynitrite-PARP cascade of cerebral ischemia/reperfusion
      injury.

PMID- 15481725
TI  - Effects of arterial geometry on aneurysm growth: three-dimensional computational
      fluid dynamics study.
AB  - OBJECT: Few researchers have quantified the role of arterial geometry in the
      pathogenesis of saccular cerebral aneurysms. The authors investigated the effects
      of parent artery geometry on aneurysm hemodynamics and assessed the implications
      relative to aneurysm growth and treatment effectiveness. METHODS: The
      hemodynamics of three-dimensional saccular aneurysms arising from the lateral
      wall of arteries with varying arterial curves (starting with a straight vessel
      model) and neck sizes were studied using a computational fluid dynamics analysis.
      The effects of these geometric parameters on hemodynamic parameters, including
      flow velocity, aneurysm wall shear stress (WSS), and area of elevated WSS during
      the cardiac cycle (time-dependent impact zone), were quantified. Unlike
      simulations involving aneurysms located on straight arteries, blood flow inertia
      (centrifugal effects) rather than viscous diffusion was the predominant force
      driving blood into aneurysm sacs on curved arteries. As the degree of arterial
      curvature increased, flow impingement on the distal side of the neck intensified,
      leading to elevations in the WSS and enlargement of the impact zone at the distal
      side of the aneurysm neck. CONCLUSIONS: Based on these simulations the authors
      postulate that lateral saccular aneurysms located on more curved arteries are
      subjected to higher hemodynamic stresses. Saccular aneurysms with wider necks
      have larger impact zones. The large impact zone at the distal side of the
      aneurysm neck correlates well with other findings, implicating this zone as the
      most likely site of aneurysm growth or regrowth of treated lesions. To protect
      against high hemodynamic stresses, protection of the distal side of the aneurysm
      neck from flow impingement is critical.

PMID- 15481726
TI  - Deep brain stimulation of the ventral caudate nucleus in the treatment of
      obsessive-compulsive disorder and major depression. Case report.
AB  - Obsessive-compulsive disorder (OCD) is an anxiety disorder associated with
      recurrent intrusive thoughts and repetitive behaviors. Although conventional
      pharmacological and/or psychological treatments are well established and
      effective in treating OCD, symptoms remain unchanged in up to 30% of patients.
      Deep brain stimulation (DBS) of the anterior limb of the internal capsule has
      recently been proposed as a possible therapeutic alternative in treatment
      resistant OCD. In the present study, the authors tested the hypothesis that DBS
      of the ventral caudate nucleus might be effective in a patient with intractable
      severe OCD and concomitant major depression. Psychiatric assessment included the
      Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Hamilton Depression Rating
      Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), and the Global Assessment
      of Functioning (GAF) Scale for determining the symptom severity of OCD,
      depression, and anxiety as well as the quality of pychosocial and occupational
      functioning, respectively. Neuropsychological assessment consisted of a wide
      range of tests primarily exploring memory and executive functions. Deep brain
      stimulation of the ventral caudate nucleus markedly improved symptoms of
      depression and anxiety until their remission, which was achieved at 6 months
      after the start of stimulation (HDRS < or = 7 and HARS < or = 10). Remission of
      OCD (Y-BOCS < 16) was also delayed after 12 or 15 months of DBS. The level of
      functioning pursuant to the GAF scale progressively increased during the 15-month
      follow-up period. No neuropsychological deterioration was observed, indicating
      that DBS of the ventral caudate nucleus could be a promising strategy in the
      treatment of refractory cases of both OCD and major depression.

PMID- 15481727
TI  - Bilateral cortical stimulation for deafferentation pain after spinal cord injury.
      Case report.
AB  - The relief of intractable pain after spinal cord injury (SCI) is very difficult
      to obtain, even with dorsal root entry zone lesioning, spinal cord stimulation,
      and thalamic stimulation. Using bilateral motor cortex stimulation (MCS) the
      authors successfully treated a woman who experienced deafferentation pain 4 years
      after sustaining an SCI. To the authors' knowledge, this is the first report of
      bilateral MCS for pain relief after SCI. The success they achieved using this
      method indicates that MCS could be a new treatment option for deafferentation
      pain following SCI.

PMID- 15481728
TI  - Cerebral venous angioma of the pons complicated by nonhemorrhagic infarction.
      Case report.
AB  - The authors emphasize an unusual complication of venous angiomas in the brain:
      venous infarction. The patient in this case is a 32-year-old man who presented
      with a clinical history of headache followed by a worsening of his neurological
      status. Neuroimaging studies demonstrated a brain infarct in the posterior fossa,
      which was related to thrombosis of the draining vein of a cerebral venous
      angioma. A conservative treatment approach without anticoagulation therapy was
      followed and the patient completely recovered. Nonhemorragic venous infarction
      caused by thrombosis of a venous angioma is exceptional and only nine previous
      cases have been reported in the literature.

PMID- 15481729
TI  - Progression of a posterior communicating artery infundibulum into an aneurysm in
      a patient with Alagille syndrome. Case report.
AB  - The authors present a case in which a posterior communicating artery (PCoA)
      infundibulum progressed into an aneurysm in a patient with Alagille syndrome
      (arteriohepatic dysplasia). The 3-mm PCoA infundibulum had been noted on
      angiography studies obtained 5 years earlier, prior to clip occlusion of a
      basilar tip aneurysm. Recently, the patient presented to the emergency department
      with the sudden onset of headache and decreased mental status. A computerized
      tomography scan of the head with three-dimensional angiography revealed no gross
      subarachnoid hemorrhage, but did demonstrate a 5-mm PCoA aneurysm. Lumbar
      puncture demonstrated xanthochromia and a large quantity of red blood cells. The
      patient underwent open surgery for aneurysm clip occlusion and obtained a good
      recovery. This case illustrates the small but growing number of examples of
      infundibulum progression. It also indicates the need for a close follow up in
      patients with congenital abnormalities that may pose an increased risk for what
      has traditionally been considered a benign lesion.

PMID- 15481730
TI  - Persistent primitive trigeminal artery-cavernous sinus fistula with intracerebral
      hemorrhage: endovascular treatment using detachable coils in a transarterial
      double-catheter technique. Case report and review of the literature.
AB  - Intracerebral hemorrhage occurred in this 61-year-old woman with preexisting
      diplopia and proptosis. Results of angiography demonstrated a persistent
      primitive trigeminal artery (PPTA)-cavernous sinus fistula with cortical venous
      reflux. Two microcatheters were introduced transarterially through the PPTA into
      the two draining pathways in the cavernous sinus. Coils were delivered in both
      pathways simultaneously to prevent further venous overload on either path. The
      fistula was successfully occluded without complication while the PPTA was
      preserved. The authors describe this double-catheter technique for coil
      embolization of a fistula and review the literature concerning PPTA-cavernous
      sinus fistulas.

PMID- 15481731
TI  - Perfusion imaging of high-grade gliomas: a comparison between contrast harmonic
      and magnetic resonance imaging. Technical note.
AB  - Transcranial contrast harmonic (CH) imaging is emerging as a promising tool for
      the evaluation of brain perfusion. The authors report on two cases of
      histologically proven high-grade gliomas evaluated using CH imaging in comparison
      to perfusion magnetic resonance (pMR) imaging. In both cases, pMR imaging results
      demonstrated a massive decrease in signal intensity and an elevated regional
      cerebral blood volume (rCBV) in the tumor region; however, signal decrease was
      less prominent and rCBV was lower in healthy brain tissue. In one patient, the
      rCBV ratio of tumor/brain was 5.0 and the maximal signal decay occurred 3.1 times
      deeper in the tumor than in the healthy brain tissue. Results of an
      ultrasonography examination using CH imaging revealed similar data: the
      tumor/brain ratio for the area under the curve, a parameter corresponding to
      rCBV, was 4.1. The maximal signal intensity in the tumor was 3.3 times greater
      than in adjacent healthy brain. Comparable data were obtained in a second
      patient. Taken together, these findings indicate that CH imaging may be a
      valuable alternative to pMR imaging. This new, cost-effective bedside ultrasonic
      technique could be helpful not only as a means of noninvasive staging of gliomas
      but also as a follow-up imaging modality to evaluate postoperative tumor
      recurrence or response to antiangiogenic therapy.

PMID- 15481732
TI  - Giant fusiform intracranial A2 aneurysm: endovascular and surgical treatment.
      Case illustration.

PMID- 15481733
TI  - William Osler at Mcgill University: the Baby Professor and his early
      contributions to neurosurgery.
AB  - Between 1870 and 1884, as both a medical student and a member of the faculty, Sir
      William Osler performed approximately 1000 postmortem examinations at McGill
      University in Montreal. He conducted 786 of these examinations during his 7 years
      (1877--1884) of service as a pathologist at the Montreal General Hospital. The
      results of these were carefully recorded and catalogued either by him or by those
      who compiled the Pathological Report of the Hospital. Included in this material
      are many early descriptions of neurosurgical disease. Osler used this information
      for subsequent teaching in both Philadelphia and Baltimore. Osler's early and
      lifelong special interest in diseases of the nervous system not only led him to
      make seminal observations but also served to initiate his influence and
      relationships with the emerging leaders in neurology and neurosurgery.

PMID- 15481734
TI  - Anterior cerebral artery.

PMID- 15481735
TI  - Seizures and subarachnoid hemorrhage.

PMID- 15481736
TI  - Dystonia.

PMID- 15481737
TI  - Treatment of hydrocephalus.

PMID- 15481738
TI  - The power of a balanced diet and lifestyle in preventing cardiovascular disease.
AB  - We examine the physiologic changes involved in the onset of cardiovascular
      disease (CVD) as well as multiple dietary and lifestyle factors that either
      promote or prevent CVD. Dietary fats (saturated, monounsaturated, n-3 and n-6
      polyunsaturated, and trans fats), antioxidants, and carbohydrates, as well as
      alcohol consumption, exercise, smoking, and infections, are evaluated.
      Epidemiologic studies and clinical trials are discussed in light of the
      underlying mechanisms.

PMID- 15481740
TI  - The medicinal uses of poi.
AB  - Poi is a pasty starch made from the cooked, mashed corm of the taro plant
      (Colocasia esculenta L.). Originating in Asia, this root crop is now found
      primarily in tropical and subtropical regions and was a major dietary staple in
      the Pacific islands. We hypothesize that poi has potential use as a probiotic
      defined by FAO/WHO as, "live microorganisms which when administered in adequate
      amounts confer a health benefit to the host." No scientific studies have explored
      the possibility of poi being used as a probiotic in medical nutrition therapy,
      however, an investigator determined that the predominant bacteria in poi are
      Lactococcus lactis (95%) and Lactobacilli (5%), both of which are lactic acid
      producing bacteria. This investigator also reported that poi contains
      significantly more of these bacteria per gram than yogurt. To determine if poi is
      beneficial for certain health conditions, a literature search was conducted to
      find all available research studies in which poi was used as a complementary
      treatment. Documented evidence suggests that poi shows promise for use in infants
      with allergies or failure-to-thrive. However, to support previous findings, more
      research needs to be conducted with poi and its potential use as a probiotic.

PMID- 15481741
TI  - Enzyme replacement as an effective treatment for the common symptoms of complex
      carbohydrate intolerance.
AB  - Complex carbohydrates are an essential part of a healthy diet. However, many
      people suffer from varying degrees of carbohydrate intolerance, resulting in
      embarrassing gastrointestinal symptoms and avoidance of these components of a
      healthy diet. To facilitate awareness and discussion, we propose the phrase
      "complex carbohydrate intolerance" (CCI) as a broad term to encompass the range
      of symptoms associated with carbohydrate intolerance. While various treatments
      offer symptomatic relief, enzyme replacement therapy targets the cause of the
      problem: an enzyme deficiency. The enzyme, alpha-galactosidase, currently only
      found in the over-the-counter product, Beano, may be an effective preventative
      treatment for CCI.

PMID- 15481739
TI  - Probiotics and medical nutrition therapy.
AB  - Probiotics have been defined by The Food Agricultural Organization/World Health
      Organization (FAO/WHO) as "live microorganisms which when administered in
      adequate amounts confer a health benefit to the host." They have been used for
      centuries in the form of dairy-based fermented products, but the potential use of
      probiotics as a form of medical nutrition therapy has not received formal
      recognition. A detailed literature review (from 1950 through February 2004) of
      English-language articles was undertaken to find articles showing a relationship
      between probiotic use and medical conditions. Medical conditions that have been
      reportedly treated or have the potential to be treated with probiotics include
      diarrhea, gastroenteritis, irritable bowel syndrome, and inflammatory bowel
      disease (Crohn's disease and ulcerative colitis), cancer, depressed immune
      function, inadequate lactase digestion, infant allergies, failure-to-thrive,
      hyperlipidemia, hepatic diseases, Helicobacter pylori infections, genitourinary
      tract infections, and others. The use of probiotics should be further
      investigated for possible benefits and side-effects in patients affected by these
      medical conditions.

PMID- 15481742
TI  - Apples in the American diet.
AB  - Apples play an important role in the American diet. They are among the most
      popular fruits consumed in the United States and are well recognized for their
      flavor and nutrition. In the last three decades, per capita consumption of
      processed apples has increased and consumption of fresh apples has declined.
      Apples are a major food source of flavonoids, antioxidants known for their free
      radical-scavenging properties. Increasing evidence from in vitro, in vivo, and
      epidemiologic studies suggest that flavonoids found in apples may be protective
      against cancer, heart disease, and other chronic diseases.

PMID- 15481744
TI  - Nonabusive physical punishment and child behavior among African-American
      children: a systematic review.
AB  - BACKGROUND: The use of nonabusive physical punishment as a form of discipline has
      been greatly debated in the scientific and popular literature. Impact on child
      behavioral outcomes has frequently been found; however, the effects of its use
      are not clear, particularly for African-American children. This systematic review
      of the literature examined the impact of exposure to nonabusive physical
      punishment on the behavior of African-American children. METHODS: A search was
      conducted of PubMed and Psyclnfo from 1970 to 2000 using the key terms: corporal
      punishment, physical punishment, disciplinary practices, and discipline and
      parenting. Studies that described ethnicity of the population and included a
      majority of a well-described African-American population were included. Each
      study was required to include measurable data on child behavioral outcomes and at
      least one measure of discipline that assessed use of nonabusive physical
      punishment in children 0-14 years of age. RESULTS: All seven included studies
      used lower socioeconomic status (SES) and/or urban African-American populations.
      Study design and rural versus urban populations differentiated beneficial and
      detrimental outcomes. In all longitudinal studies, African-American children had
      beneficial or neutral outcomes. DISCUSSION: This review suggests that it is
      possible that there are benefits to nonabusive physical punishment for African
      American children. However, needed are further longitudinal studies that better
      assess the multiple confounders that impact the use of discipline, such as SES,
      parental education level, and exposure to community or domestic violence.

PMID- 15481743
TI  - Managing pain: The Challenge in Underserved Populations: Appropriate Use Versus
      Abuse and Diversion.
AB  - ISSUE: Inadequate pain management is a serious public health problem that affects
      a wide cross-section of Americans. Patients are often denied sufficient
      medication, because physicians lack training and fear scrutiny from federal and
      state regulatory agencies. In addition, even the state-financed system of care,
      Medicaid, has been increasingly denying payment for the best treatment for pain
      management. These factors are complicated by physician bias about various
      subgroups and poor physician-patient communication. Comprehensive patient
      assessment plays a crucial role in determining appropriate treatment and
      identifying potential abuse problems. Physicians must routinely document
      medications analgesic effects and screen for potential ill effects and drug
      abuse. OBJECTIVE: To examine the prevalence of the undertreatment of pain,
      particularly among African Americans, and to recommend relevant proactive policy
      and practice changes to aid in eliminating this health problem. CONSENSUS
      PROCESS: In July 2002, the NMA convened the "Managing Pain: The Challenge in
      Underserved Populations: Appropriate Use versus Abuse and Diversion" Consensus
      Meeting in Washington, DC. The country's most renowned experts in the area of
      pain management and substance abuse reviewed substantial information regarding
      pain management and substance abuse including the following: --A draft summary
      paper on pain management and substance abuse that served as briefing material for
      consensus members; --Annotated bibliographies; --Articles on pain management and
      substance abuse; and --Key presentations on pain management and substance abuse.

PMID- 15481745
TI  - Modifiable determinants of healthcare utilization within the African-American
      population.
AB  - BACKGROUND: Significant health disparities directly affect the African-American
      population. Most previous studies of disparities in access to and utilization of
      healthcare have focused on black-white differences rather than focusing on
      "within-group" analysis of African Americans. OBJECTIVE: To tease out the
      differential effects of modifiable risk factors (such as health insurance, usual
      source of care, and poverty) from personal characteristics (age, gender, rural
      residence) on healthcare utilization within the African-American population.
      METHODS: Secondary data analysis of 3462 records from African-American
      respondents to the 1999 Medical Expenditure Panel Survey (MEPS) Household File, a
      nationally representative survey of the civilian, noninstitutionalized U.S.
      population in 1999. RESULTS: We found significant variation in the number of
      office visits, outpatient clinic visits, hospital discharges, days hospitalized,
      and fills of prescribed medication among 3462 African-American respondents who
      represent a U.S. population of 36,538,639 persons. Personal nonmodifiable
      characteristics such as age and gender were significantly related to healthcare
      utilization. Poverty and rural residence were also significantly correlated, but
      the strongest modifiable predictors of healthcare utilization for Afrcan-American
      persons in 1999 were whether or not individuals had health insurance and/or a
      usual source of care. Emergency department visits were the only form of care that
      showed remarkably little variation based on these modifiable risk factors.
      CONCLUSIONS: The three modifiable factors of poverty, uninsurance, and having a
      primary care medical home have a dramatic effect on patterns of care for African
      American patients and could be independently targeted for intervention.

PMID- 15481746
TI  - Greater hepatic vulnerability after alcohol intake in African Americans compared
      with Caucasians: a population-based study.
AB  - AIMS OF THE STUDY: In the last 40 years, African Americans have experienced
      higher age-adjusted liver cirrhosis mortality rates than whites. Alcohol use has
      been hypothesized to be the likely determinant of this disparity in liver disease
      mortality. This study was aimed at evaluating racial variations in common
      biomarkers of liver injury, such as gamma-glutamyltransferase (GGT), aspartate
      amino transferase (AST) and alanine amino transferase (ALT), by categories of
      drinking status and levels of current alcohol use. METHODS: A cross-sectional
      analysis of a general population sample of 3304 residents of Erie and Niagara
      counties in New York State, 35-80 years of age and free from known hepatic
      disease, stratified by racial group (African-American and white). RESULTS:
      Concentrations of GGT were higher for African-Americans than for whites in all
      categories of drinking status (lifetime abstainers, former and current drinkers)
      after adjustment for potential confounders (age, sex, education, smoking, and
      body mass index). However, differences in enzyme mean values between the two
      racial groups were consistently larger among current drinkers than for either
      lifetime abstainers or former drinkers. In analyses based on tertiles of alcohol
      consumption in the last 30 days, differences in GGT mean values between the two
      races tended to amplify with increasing amounts of consumption. CONCLUSIONS:
      These findings seem to support the hypothesis of greater sensitivity to alcohol
      induced hepatotoxicity among African-Americans than for whites.

PMID- 15481747
TI  - Bronchioloalveolar carcinoma in African Americans.
AB  - PURPOSE: To review the clinical and pathophysiologicol features of
      bronchioloalveolar carcinoma (BAC) in African Americans. PATIENTS AND METHODS:
      This is a retrospective review of 19 cases of BAC at Howard University Hospital
      between 1984 and 1999. Twenty-seven cases were identified. Medical records of 19
      patients (15 men and four women) were available for review. The pathological
      reports were reviewed. The clinical and pathological features of this disease
      were compared with another study by Feldman et al. from the Mayo Clinic reporting
      25 Send patients (predominantly Caucasians) with metastatic BAC. RESULTS: Of 835
      cases of lung cancers diagnosed at our institution between 1984 and 1999, 27
      cases of BAC were identified. Only 19 charts were available for review from the
      Howard University (HU) tumor registry. These were not consecutive cases. Four of
      19 (21%) HU cases were nonsmokers compared to eight of 25 (32%) Mayo cases p =
      0.51). Productive cough was the most common symptom in both HU and Mayo patients,
      and was less common in HU patients than Mayo patients (26% versus 68%: P =
      0.008). In contrast, hemoptysis occurred in 16% of patients in both institutions
      (p = 1.00). Other studies have reported cough to be mostly nonproductive.
      Pathological review showed mucinous BAC accounting for 21% (four cases),
      nonmucinous for 68% (13 cases), and sclerotic for 10% (two) of cases. Earlier
      studies have reported 50% incidence of mucinous BAC. Sixteen had surgical
      resections (eight wedge, seven lobectomy, one segmentectomy). Eight patients
      received radiotherapy. Response to chemotherapy was poor, with average survival
      of nine months. Overall, average survival was 23 months (seven days to seven
      years). Eight out of nine patients who presented with stage-1 disease underwent
      wedge resection were noted to have the best five-year survival (75%). Five
      patients presented with stage-2, and three patients with stage-3 disease. Two
      patients who presented with stage-4 diease and received chemotherapy alone had
      the worst survival (mean seven months). Further subclassification into stages A
      and B were not available from the chart. CONCLUSION: Our study is the first
      published review of clinical and pathophysiological features of BAC in African
      Americans. The study showed differences in the clinical features, histopathology,
      and radiological features among Caucasians and African Americans.

PMID- 15481748
TI  - Biochemical observations in Blount's disease (infantile tibia vara).
AB  - Blount's disease or congenital tibia vara is a clinical entity characterized by
      tibia bowing, tibia torsion, and beaking of the medial tibia metaphysis on plain
      radiograph. In our environment, burnt-out rickets patients with biochemical and
      radiological diagnosis of rickets who after treatment still have residual bone
      changes despite normal bone biochemistry) can also present with similar clinical
      and radiological features as Blount's disease. However, certain biochemical
      variations, including antioxidants, may serve as a basis for differentiation
      between these two disorders. The serum levels of calcium, inorganic phosphate,
      zinc, copper, and alkaline phosphatase in 15 patients (10 females and five males)
      aged between two- and five years (mean 3.8 +/- 1.1 (SD)) with clinical and
      radiological features of Blount's disease were determined. The mean weight of the
      patients with Blount's disease was 14.0 +/- 2.4 kg (range: 11.5-16.3 kg). Fifteen
      subjects (nine females and six males) matched for age and sex without clinical
      features of any metabolic bone and/or nutritional diseases who were attending the
      surgical outpatient clinic served as control subjects. The serum concentrations
      of inorganic phosphate and calcium, though lower in patients with Blount's
      disease compared with controls, did not reach statistical significance. Alkaline
      phosphatase activity was increased in the serum of all patients with Blount's
      disease. In addition, there was an observed significant reduction in serum
      concentration of zinc (P < 0.03) compared to the control subjects. As for calcium
      level, the concentration of serum copper in Blount's patients was reduced, but
      this was not statistically significant. These biochemical observations,
      especially those of the antioxidant micronuent zinc, may serve as a basis for the
      differentiaion of the sometimes clinically inseparable disorders of Blount's and
      rckets and may aid in early differential diagnosis, appropriate treatment as well
      as prevention of complications.

PMID- 15481749
TI  - African-American menthol and nonmenthol smokers: differences in smoking and
      cessation experiences.
AB  - BACKGROUND: Despite smoking fewer cigarettes per day, African Americans have
      lower cessation rates and experience disproportionately higher rates of smoking
      related health consequences. Because of their high preference for menthol
      cigarettes, it has been suggested that smoking menthol cigarettes may contribute
      to the excess smoking-related morbidity experienced by African Americans. Smoking
      menthol cigarettes could increase health risks from smoking if smokers of menthol
      cigarettes have lower cessation rates and thereby have longer duration of smoking
      compared to smokers of nonmentholated cigarettes. Few studies have examined
      associations between smoking of mentholated cigarettes and smoking cessation
      among African Americans. This study examined the smoking patterns of menthol
      cigarette smokers and their smoking cessation experiences. METHODS: A cross
      sectional survey of 480 African-American smokers at an inner-city health center.
      Survey examined sociodemographics, smoking characteristics, and smoking cessation
      experiences of participants. Menthol smokers (n = 407) were compared to
      nonmenthol smokers (n = 73) in these characteristics. RESULTS: Menthol smokers
      were younger and more likely to smoke cigarettes with longer rod length, with
      filters, and those high in nicotine and tar. Although both groups did not differ
      by number of past quit attempts, time since most recent quit attempt was shorter
      for menthol smokers. The durations of most recent and longest-ever quit attempts
      were nonsignificantly shorter for menthol, compared to nonmenthol smokers.
      CONCLUSIONS: These data suggest that African-American menthol smokers are less
      successful with smoking cessation. Prospective studies are needed to confirm
      these findings and examine mechanisms underlying such differences.

PMID- 15481750
TI  - Thrombocytopenia in malaria.
AB  - Malaria continues to be a cause of high mortality and morbidity. Imported cases
      of malaria are increasing in New York City. Yet, New York physicians, when
      evaluating patients for fever, frequently missed the diagnosis of malaria. We
      evaluated the role of platelet count for predicting malarial infection. The study
      included patients seen between 1996 and 2000 in a New York community hospital for
      fever who had traveled to a malaria-endemic area. Forty patients with malaria
      were identified. Our study found the sensitivity of platelet count for diagnosing
      malaria was 100%, and the specificity was 70%. The negative predictive value was
      100% and the positive predictive valve was 86%. Hence, we propose that in any
      patient with fever and recent travel history, platelet count is an important clue
      to the diagnosis of malaria. A finding of thrombocytopenia should increase the
      suspicion of malaria and lead to performance of more specific tests, including
      multiple peripheral smears and ELISA for parasite-specific antigen, etc.

PMID- 15481751
TI  - Percutaneous renal biopsy as an outpatient procedure.
AB  - Percutaneous renal biopsy (PRB) is a safe and effective tool in the diagnosis and
      management of renal disease. It is the gold standard for evaluating renal
      parenchymal disease. It is both useful for diagnosis and monitoring progress of
      renal diseases. Where facilities and personnel are available to carry out the
      procedure in developing countries, it has become increasingly difficult for
      patients to pay for hospital admission fees, the procedure, and processing of the
      samples obtained. Information on the success rate and safety of the procedure is
      of interest to nephrologists for cost-benefit considerations and medicolegal
      purposes. This paper reports the outcome of outpatient PRB done among patients of
      the University College Hospital, Ibadan, Nigeria. With the use of ultrasound
      guidance, PRB remains a safe procedure and can be done on an outpatient basis.

PMID- 15481752
TI  - Misconceptions of hypertension.
AB  - A prospective questionnaire study of the misconceptions of hypertension by
      hypertensive patients was carried out in 1365 male and female hypertensive
      patients aged between 21-80 years. About 40% of the study population could not
      define hypertension, but even those who did appeared to be in denial of the
      disease. About 24% were unaware of the causes of hypertension; the most common
      cause mentioned was psychosocial stress. Between 0.6% and 14% of subjects were
      unaware of the effect of risk factors, like obesity, cigarette smoking, exercise,
      excessive alcohol and salt consumption, or hypertension. Interestingly, some feel
      that regular sexual intercourse worsens hypertension. Eight percent of subjects
      had no fear of the effect of poor compliance to antihypertensive medication,
      while 10% were anxious about the heavy financial burden imposed by hypertension
      management, Sixty-five percent of subjects feel that they will require no more
      medication once they achieve control of their blood pressure. Twenty-one percent
      of respondents are of the opinion that they will achieve a permanent cure only
      from alternative medical practitioners and will consider using alternative
      medicine in future. The study confirms the importance of medical education for
      patients irrespective of their level of education, as many of these patients
      still entertain that gross misconceptions may have negative impact on outcome.

PMID- 15481753
TI  - Focal origin of ventricular fibrillation in a patient with ischemic
      cardiomyopathy.
AB  - A 65-year-old patient with history of ischemic cardiomyopathy admitted to the
      hospital for chest pain and subsequently experienced incessant ventricular
      fibrillation (VF), requiring repeated defibrillation. Coronary angiogram was
      unchanged, compared to a study a year before, and acute ischemia was not
      considered to be the etiology of the VF. A particular premature ventricular
      contraction morphology was noted on telemetry prior to each episode of VF. The
      patient subsequently underwent successful radiofrequency ablation of a focus in
      the left ventricular free wall. Careful examination of initiating foci of VF or
      polymorphic ventricular tachycardia, with radiofrequency ablation in appropriate
      cases, could be potentially life-saving.

PMID- 15481754
TI  - Melanonychia striata with multiple toenail involvement in a child.
AB  - A 10-year-old Filipino boy with melanonychia striata affecting six toenails is
      described. The occurrence of melanonychia striata affecting so many toenails has
      not been reported previously in a Filipino child.

PMID- 15481755
TI  - Acute hepatic sequestration in sickle cell disease.
AB  - Sickle cell anemia is a disease that affects one out of every 600 African
      Americans. It is often debilitating and can cause many physical restrictions to
      individuals with the disease. The disease has many complications which can be
      vexing for patients and their physicians. The hepatic complications attributed to
      vascular occlusion encompass a variety of clinical syndromes of which the
      relationship among clinical presentation, biochemical findings, and histologic
      features remains unclear. The conditions range from the self-limiting hepatic
      right upper quadrant syndrome (hepatic crisis) to the potentially lethal
      intrahepatic cholestasis and acute hepatic sequestration syndromes. Few cases
      have been documented, and there have not been many sizable studies on acute
      hepatic sequestration in sickle cell disease. This case is useful for clinicians
      who are not familiar with the intrahepatic vaso-occlusive syndromes in sickle
      cell disease. It provides insight into the presentation, diagnosis, and
      management of these syndromes.

PMID- 15481756
TI  - Soybean foods--the good, bad, and ugly.

PMID- 15481757
TI  - Web of science: index not as useful as it appears.

PMID- 15481758
TI  - Succinct language when referring to historically underserved minority
      populations.

PMID- 15481759
TI  - The effects of weight loss treatments on upper and lower body fat.
AB  - The intra-abdominal visceral deposition of adipose tissue, which characterises
      upper body obesity, is a major contributor to the development of hypertension,
      glucose intolerance and hyperlipidaemia. Conversely, individuals with lower body
      obesity may have comparable amounts of adipose tissue but remain relatively free
      from the metabolic consequences of obesity. This raises an obvious question-are
      there particular weight reducing treatments which specifically target intra
      abdominal fat? In theory, surgical removal of upper body fat should be effective.
      In reality, neither liposuction nor apronectomy ('tummy tuck') have any
      beneficial metabolic effects, they simply remove subcutaneous adipose tissue
      which is often rapidly replaced. Vertical banded gastroplasty and gastric bypass
      operations may be dramatically effective in improving blood pressure, insulin
      sensitivity and glucose tolerance. However, these benefits result from a parallel
      reduction in visceral and total body fat. Studies of body fat distribution in
      postmenopausal women confirm that the marked decrease in adiposity, following a
      programme of very low calorie diet and exercise, reflects a comparable reduction
      in visceral and thigh fat. The reduction in waist circumference after a low
      fat/exercise programme suggests a similar situation in men. Exercise has an
      important role in treatment but, once again, the fat loss is generalised.
      Nevertheless, the improved metabolic parameters seen in exercising obese
      subjects, independent of weight loss, suggest other beneficial actions. Growth
      hormone (GH) has a marked lipolytic action. GH replacement treatment for GH
      deficient adults with pronounced abdominal fat deposition, has been shown to
      reduce intra-abdominal fat by 47% compared to 27% decrease in abdominal
      subcutaneous fat. Similar beneficial actions on abdominal fat have been reported
      following treatment with testosterone in obese men. The potential hazards of such
      treatments make them unsuitable therapy for obesity. Dexfenfluramine is effective
      in reducing total body fat but the results from a six month randomised controlled
      trial indicates that it does not specifically influence changes in waist
      circumference associated with weight loss. In conclusion, any treatment which
      reduces total body fat will, by its nature, reduce intra-abdominal visceral fat.
      There are presently no specific treatments which can be recommended for intra
      abdominal fat but increasing knowledge of the biochemical aberrations associated
      with visceral adiposity may lead to more specific therapies for the future.

PMID- 15481760
TI  - Visceral fat in relation to health: is it a major culprit or simply an innocent
      bystander?
AB  - The aim of this review is to look critically at the widely accepted notion that
      visceral fat accumulation is the main determinant of obesity related diseases.
      Most of the epidemiological evidence is based on anthropometric indicators of
      fatness and fat distribution and their implications for visceral fat accumulation
      may not be unequivocal. In most cross-sectional studies in which visceral fat is
      associated with the level of risk factors or presence of disease, no adjustment
      is made for potential confounders. There are potential confounders at different
      levels of the causal chains linking visceral fat to health. Firstly, there are
      aspects of body composition or fat depots associated with visceral fat
      accumulation such as total body fat or total subcutaneous fat. Total and
      subcutaneous fat are, by themselves, potentially strong determinants for
      metabolic disturbances and disease. Secondly, there are behavioural factors (for
      example smoking, alcohol consumption, physical activity, dietary habits) which
      have been found to be associated with both the amount of visceral fat and health
      outcomes. Thirdly, there are hormonal mechanisms (adrenal and gonadal steroids as
      well as growth hormone) which may affect both the accumulation of visceral fat as
      well as the development of diseases. Finally, even if associations between
      visceral fat and risk factors or presence of diseases would be firmly
      established, the causality of the observed associations may not always be easy to
      interpret. Prospective studies are needed with appropriate control of potential
      confounding variables. It is concluded that, based on the current evidence, it is
      difficult to quantify the independent contribution of visceral fat to the
      development of a variety of chronic diseases.

PMID- 15481761
TI  - Association between anthropometric and ultrasound measurements of fatness with
      ambulatory blood pressure monitoring in obese women.
AB  - OBJECTIVE: An association between body fat distribution indices and the amount of
      visceral adipose tissue (AT) with blood pressure (BP) has been documented.
      However, most studies used casual morning BP values as the dependent variable.
      The aim of our study was to identify which of the obesity indices (the body mass
      index (BMI), waist-to-hip ratio (WHR), sagittal diameter or visceral (AT)
      measured by ultrasonography (US)) better correlated with BP determined by 24 h
      ambulatory monitoring. DESIGN: Retrospective study on obese women, outpatients at
      the Obesity Clinic, Internal Medicine Institute, Chieti University, Italy.
      SUBJECTS AND MEASUREMENTS: In fifty-one obese outpatient women, BP was determined
      with a single morning measurement (casual BP) and with 24 h ambulatory monitoring
      (ABPM). The obesity parameters were the BMI, WHR, sagittal diameter and the
      amount of intra-abdominal and subcutaneous fat determined by US. RESULTS: Except
      for the BMI, all obesity indices as WHR, sagittal diameter and visceral AT
      measured by US were strongly correlated with both casual and 24 h ambulatory BP
      values. When such parameters were evaluated in a multivariate analysis, only the
      WHR remained significantly related to 24 h ABPM parameters and not to casual
      values. CONCLUSIONS: These results suggest that a simple measure of fat
      distribution as the WHR could represent a good predictor of hypertension in
      obesity, providing that BP is measured in a more reproducible manner, such as by
      24 h ambulatory BP monitoring.

PMID- 15481762
TI  - Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy
      adults.
AB  - OBJECTIVE: To investigate whether the substitution of fish oil for visible fats
      in a control diet (52% carbohydrates, 16% protein, 32% fat; P:S 0.2) influences
      body fat mass and substrate oxidation in healthy adults. DESIGN: Six volunteers
      (5 men; 23 +/- 2 y; BMI: 21.9 +/- 1.6) were fed a control diet (C) ad libitum
      during a period of three weeks and, 10-12 weeks later, the same diet where 6 g/d
      of visible fat were replaced by 6 g/d of fish oil (FO) for another three weeks.
      RESULTS: Energy intakes (IKA-calorimeter) were unchanged. Body fat mass (Dual
      energy X-ray absorptiometry) decreased with FO (-0.88 +/- 0.16 vs -0.3 +/- 0.34
      kg; FO vs C; P < 0.05). When adjusted for lean body mass (Ancova), resting
      metabolic rate (indirect calorimetry) was unchanged. Basal respiratory quotient
      decreased with FO (0.815 +/- 0.02 vs 0.834 +/- 0.02; P < 0.05) and basal lipid
      oxidation increased with FO (1.06 +/- 0.17 vs 0.87 +/- 0.13 mg kg(-1) min(-1); P
      < 0.05). CONCLUSION: Dietary FO reduces body fat mass and stimulates lipid
      oxidation in healthy adults.

PMID- 15481763
TI  - Moderate weight reduction improves red cell aggregation and factor VII activity
      in overweight subjects.
AB  - OBJECTIVE: To investigate the effect of a dietary intervention to reduce body
      weight on red cell aggregation (RCA), factor VII activity, plasminogen activator
      inhibitor (PAI) activity, tissue plasminogen activator (t-PA) antigen,
      fibrinogen, whole blood and plasma viscosity, haematocrit and lipids. DESIGN:
      Open single stranded study of dietary intervention for weight loss in a volunteer
      sample. SUBJECTS: Forty-five subjects whose BMI exceeded 26 kg/m2 were recruited
      and received dietetic advice designed to reduce body weight by 0.5 kg per week.
      MEASUREMENTS: Body weight and waist and hip circumferences, dietary intake by
      seven day weighed inventory, RCA, factor VII activity, PAI activity, t-PA
      antigen, fibrinogen, whole blood and plasma viscosity, haematocrit and lipids.
      RESULTS: After 12 weeks of dietary intervention there were reductions in body
      weight and BMI by 5.9 (s.d. 3.3) kg and 1.9 (s.d. 1.0) kg/m2 respectively in
      males, and 4.1 (s.d. 2.9) kg and 1.6 (s.d. 1.1) kg/m2 in females (P < 0.0001).
      Factor VII activity (P = 0.0043), RCA (P = 0.01) and t-PA antigen (P = 0.016)
      were reduced in females after weight reduction but no differences were found in
      PAI activity, whole blood, plasma viscosity or haematocrit. The changes in factor
      VII activity and RCA were appropriate for the changes in BMI on the basis of the
      relationships of the risk factors with BMI in a cross sectional survey of a
      representative Scottish population. Plasma total cholesterol was reduced (P =
      0.016) but HDL cholesterol and triglycerides remained unchanged. There were
      significant associations between the reductions in factor VII activity and BMI (r
      = 0.395, P = 0.013) and between the reductions in RCA and waist to hip ratio (r =
      0.350, P = 0.04). No relationship was seen between changes in serum cholesterol
      and changes in factor VII activity or RCA. CONCLUSIONS: Modest weight loss, of 5%
      body weight, with conventional dietary intervention reduces two established risk
      factors for ischaemic heart disease (factor VII activity and RCA) which are
      generally elevated in those with increased body weight.

PMID- 15481764
TI  - Impairment of antidiuretic hormone and atrial natriuretic peptide regulation in
      the obese woman with a swelling syndrome and an increase in capillary
      permeability to albumin.
AB  - OBJECTIVE: To study the regulation of antidiuretic hormone (ADH) and atrial
      natriuretic peptide (ANP) in obese and lean women with a swelling syndrome.
      PATIENTS: Thirty-four obese women and 12 lean women with a swelling syndrome and
      an abnormal isotopic test of capillary permeability to albumin were investigated.
      MEASUREMENTS: After 10 nocturnal hours of fluid restriction, subjects were asked
      at 8am to ingest a tap water load of 20 ml/kg within 10 min and to remain
      strictly recumbent until twelve noon on the first day, and to remain standing and
      to walk around until twelve noon on the second day. Free water clearance and the
      cGMP/creatinine and albumin/creatinine ratios were determined hourly in the
      morning. RESULTS: The total 4 h-urinary volume/ingested water volume ratio was
      significantly lower on the second day both in the lean and the obese patients,
      the differences being slightly larger in the obese patients. The increase in free
      water clearance was significantly less on the second day in the obese patients.
      The increase in cGMP/creatinine ratio was also significantly lower on the second
      day in the obese patients. The maximum level of the urinary albumin/creatinine
      ratio was significantly higher on the second day in the obese patients.
      CONCLUSION: In obese women with a swelling syndrome: (1) The higher increase in
      the urinary albumin excretion rate after water loading followed by a sustained
      upright position suggests a widespread alteration in capillary function, which is
      also indicated by the isotopic test of capillary permeability to albumin. (2) The
      water load-induced inhibition of ADH secretion and stimulation of ANP secretion
      or ANP activity, more defective in the upright position than in the recumbent
      one, is probably another major contributing factor to orthostatic oedema.

PMID- 15481765
TI  - Evaluation of signal-averaged electrocardiogram in healthy obese women: effects
      of subcutaneous adipose tissue.
AB  - OBJECTIVE: To determine the correlations between signal-averaged
      electrocardiography (SAECG) indices and various anthropometric parameters in
      obese women. SUBJECTS: Twenty-seven healthy obese women (mean age 29.7 +/- 9.6 y,
      mean body mass index 35.2 +/- 6.0 kg/m2). MEASUREMENTS: SAECG was performed using
      a Marquette, MAC 12/15 system. Bidirectional filtering, low-pass filtering 250 Hz
      and 25, 40 and 80 Hz high-pass filter settings were employed on the same averaged
      beats. At least 200 beats were averaged to achieve a noise level <1 microV. Body
      mass index, waist to hip circumference ratio, neck circumference, arm
      circumference and conicity index were determined for all subjects. Skinfold
      thicknesses were measured in triceps, biceps, subscapular, supra-iliac and para
      umbilical regions. RESULTS: Significant correlations were observed between the
      root mean square (RMS) voltage of the terminal 40 ms of the filtered ORS complex
      at 25 and 40 Hz and skinfold thicknesses measured at different sites. Significant
      correlations were obtained between the noise level at 25 and 40 Hz and skinfold
      thicknesses measured at subscapular, biceps and triceps regions also. The only
      SAECG parameter correlated significantly with the noise level was the RMS voltage
      at 25 and 40 Hz high-pass filter settings. CONCLUSIONS: In obese women SAECG must
      be performed with 80 Hz high-pass filter setting which eliminates the random
      noise originating from the subcutaneous adipose tissue. In addition RMS voltage
      which shows positive linear correlations with the noise level of 25 and 40 Hz
      high-pass filter settings might be inappropriate for the definition of abnormal
      SAECG criteria in obese women.

PMID- 15481766
TI  - Is an ephedrine caffeine treatment contraindicated in hypertension?
AB  - OBJECTIVES: To examine how the slimming drug, Letigen, containing ephedrine (E)
      20 mg and caffeine (C) 200 mg (E + C), affects blood pressure in normotensive and
      hypertensive patients treated with adrenergic beta-receptor blocking drugs and/or
      other antihypertensive agents, during a period of six weeks. DESIGN: A double
      blind, randomised, placebo controlled study of five parallel groups of overweight
      patients from general practices. SUBJECTS: One hundred and thirty-six patients
      with Body Mass Index (BMI) > 25 kg/m2 were included consecutively by 25 general
      practitioners in Denmark and randomized into five groups: (1) Hypertensive
      patients treated with betablockers and E + C; (2) Hypertensive patients treated
      with antihypertensive agents other than betablockers, and E + C; (3) Normotensive
      patients treated with E + C; (4) Hypertensive patients under any antihypertensive
      treatment + placebo; and (5) Normotensive patients + placebo. All patients were
      instructed in a 1200 kcal (= 5040 kj) diet. RESULTS: Of a total of 136 patients
      aged 20-74 y, 112 completed the study protocol. Fluctuations in systolic and
      diastolic blood pressure were seen in all groups. The systolic blood pressure was
      reduced significantly (5.5 mmHg) in the patients treated with antihypertensive
      agents other than betablockers, plus E + C. In the other hypertensive groups the
      reduction in blood pressure was not significant. In normotensive patients treated
      with E + C, the systolic and the diastolic blood pressure declined significantly
      (4.4/3.9 mmHg). At the end of the treatment period heart rate had increased
      significantly (4.9 beats/min) in the group of normotensive patients treated with
      E + C. Blood pressure and heart rate measured by the patient at home showed
      similar fluctuations from baseline prior to and during treatment with E + C or
      placebo. A mean loss of weight of approximately 4 kg in 6 weeks was significant
      for all the groups. There was no significant difference between the groups during
      this short period of treatment. In 56% of the patients treated with E + C
      complaints/side-effects related to the medical treatment were found at
      questioning. Corresponding complaints occurred in 21% of the placebo treated
      patients. In the E + C treated group 7% dropped out due to side-effects. In the
      placebo group there were no drop-outs. CONCLUSIONS: This study does not support
      the assumption that E + C should cause rises in blood pressure, acutely or during
      shortterm treatment, in either normotensive or hypertensive obese patients. The
      antihypertensive effect of the betablockers was not reversed by E + C.

PMID- 15481767
TI  - Association of anthropometric indices with elevated blood pressure in British
      adults.
AB  - OBJECTIVE: To investigate which of six anthropometric indices was most strongly
      associated with elevated blood pressure and frank hypertension in a
      representative population sample of young and middle-aged British adults.
      SUBJECTS: A representative random sample of British adults (2712 men and 3279
      women) aged between 18 and 64y, who were resident in England, Scotland and Wales,
      were studied in the 1984-85 Health and Lifestyle Survey. MEASUREMENTS: Following
      an interview where demographic, health and lifestyle details were recorded,
      measurements of height, weight and waist and hip circumference were made by a
      nurse at a home visit, where blood pressure and medication to control blood
      pressure were also recorded. BMI and the ratios of waist circumference to height
      (WHTR) and waist circumference to hip (WHR) were calculated. Respondents with a
      blood pressure above 140 mm Hg (systolic) and/or 90 mm Hg (diastolic) or who were
      being treated for hypertension were classified as having elevated blood pressure.
      RESULTS: For men and women aged 18-39 and 40-64 y the prevalence of elevated
      blood pressure increased across the quintiles of BMI, weight, waist, WHTR and WHR
      was P < 0.001 for each, with waist and WHTR having the highest odds ratios. Waist
      and height adjusted for each other were independently related to the prevalence
      of elevated blood pressure in 40-64 y old men and women. Height, on its own, was
      inversely related (P < 0.05) only in the 40-64 y old men. The age adjusted
      partial correlations between systolic and diastolic blood pressure measurements
      and the measurements of BMI, weight, waist, WHTR and WHR were close and
      significant, P < 0.001 for each. The ranking and significance of the correlations
      were hardly affected by excluding the treated hypertensives. CONCLUSIONS: The
      prevalence of elevated blood pressure was associated with quintiles of BMI,
      waist, WHTR, WHR and weight, with WHTR and WHR having the highest odds ratios.
      Waist and height were independently related to the prevalence of elevated blood
      pressure.

PMID- 15481768
TI  - Regulation of ammonia-metabolizing enzymes expression in the liver of obese rats:
      differences between genetic and nutritional obesities.
AB  - OBJECTIVE: To determine the expression of carbamoylphosphate synthetase (CPS) and
      glutamine synthetase (GS) in two different models of obese rats: genetically
      obese rats and diet obese rats. SUBJECTS: Lean and genetically obese (fa/fa)
      Zucker rats were used. DESIGN: Lean animals (30-60 d old) were fed for 30 d with
      standard chow pellets or with a hypercaloric cafeteria diet. Genetically obese
      rats were fed with standard chow pellets. MEASUREMENTS: Enzyme activity, protein
      (Western blot) and mRNA (Northern blot) contents of CPS and GS were measured in
      liver homogenates. RESULTS: In genetically obese animals CPS mRNA content was
      higher, and GS mRNA content was lower than in control animals; CPS protein
      content did not change and CPS activity was lower than in control rats. Diet
      obese rats had higher levels of CPS and GS mRNAs than control animals; GS protein
      content and activity was higher than in the control group and at the same time,
      CPS activity was very low. CONCLUSIONS: In the genetically obese animals the
      expression of CPS and GS is mainly regulated at the pre-translational level,
      whereas in the diet obese rats there is a noticeable post-translational
      component. A reciprocal regulation between CPS and GS can be established at pre
      translational levels, whereas at post-transcriptional levels it cannot. It can be
      concluded that in diet-obese animals the mechanisms involved in retaining
      nitrogen (low CPS activity) are modulated at the post-translational level.

PMID- 15481769
TI  - Relation between obesity in young adulthood and risk of non-insulin-dependent
      diabetes mellitus.
AB  - OBJECTIVE: To investigate the independent effect of obesity in young adulthood on
      the risk of non-insulin-dependent diabetes mellitus (NIDDM). DESIGN:
      Retrospective cohort design. SUBJECTS: One-thousand, one hundred and five
      Japanese male railway employees aged 30 y or older who received a health
      examination from February to May 1995. MEASUREMENTS: Adjusted odds ratios (ORs)
      for subsequent NIDDM determined by the WHO criteria or a physician's diagnosis,
      among men who were obese at ages 20, 25, or 30 y. RESULTS: Men who were obese
      (BMI > or = 25.0 kg/m2) at ages 25 or 30 y had significantly positive ORs for
      NIDDM after adjustment for age and maximum BMI (8.20 and 3.94, respectively). Men
      in the top quintile of BMI at any age also had significantly positive ORs for
      NIDDM (2.13, 7.92, and 3.49, at 20, 25, and 30 y, respectively). After mutual
      adjustment for BMI at age 20, 25 and 30 y, only obesity at age 25 y demonstrated
      a significantly positive OR for NIDDM in both absolute and relative models (6.98
      for BMI > or = 25.0 and 9.99 for the top quintile, respectively). CONCLUSION: Men
      who were obese (BMI > or = 25.0 kg/m2 or top quintile) at age 25 y were at
      significantly high risk of prevalent NIDDM in subsequent years, independent of
      age, maximum BMI, and BMIs at age 20 and 30 y.

PMID- 15481770
TI  - Adiposity, cardiac size and precursors of coronary atherosclerosis in 5 to 15
      year-old children: a retrospective study of 210 violent deaths.
AB  - OBJECTIVE: To determine the relationship between cardiac size and various
      measures of adiposity in children and the occurrence of coronary fatty streaks in
      relation to childhood obesity. DESIGN: A retrospective study based on 210 medico
      legal autopsies of 5-15 y old children who had suffered violent death in the
      Province of Oulu, Finland, in 1970-1995. METHODS: Autopsy reports with attached
      clinical data and police records were recovered from the archives of the
      Department of Forensic Medicine, University of Oulu, Finland. All 5-15 y old
      individuals who had died of external trauma and were not documented as having had
      any chronic illnesses were chosen for investigation. The following data were
      extracted from the papers: age, sex, height, body weight, heart weight, liver
      weight, total weight of the kidneys, thickness of the abdominal subcutaneous fat
      and description of the coronary arteries. Heart weight was indexed to height2.7,
      and liver weight and kidney weight were indexed to body weight, body surface area
      and height. The ponderal index (body weight/height3) was calculated, and relative
      body weight was determined as the percentage deviation of the weight from the
      mean weight for height according to a growth chart developed for Finnish
      children. RESULTS: The average absolute heart weight and heart weight/height2.7
      were significantly higher in the boys than in the girls over 12 y of age.
      Abdominal subcutaneous fat was thicker in the girls, but there were no
      significant differences in the other indicators of obesity. After adjusting for
      age, there were significant positive correlations between the ponderal index and
      heart weight/height2.7 in both the boys (P = 0.000) and the girls (P = 0.038),
      between relative body weight and heart weight/height2.7 in the boys (P = 0.000)
      and the girls (P = 0.027), and between abdominal subcutaneous fat thickness and
      heart weight/height2.7 in the boys (P = 0.045) but not in the girls (P = 0.234).
      Multiple linear regression analysis showed the ponderal index to be a significant
      predictor of heart weight/height2.7. Coronary intimal fatty streaks were
      documented in six individuals (2.9%), five of them having a ponderal index above
      the average and all of them having a relative weight above the average. Kidney
      weights were higher in the boys and were positively correlated with the measures
      of obesity and with heart weight/height2.7. CONCLUSIONS: The results point to an
      important role of excess body weight and adiposity in the development of early
      myocardial and coronary changes in childhood: coronary fatty streaks were not
      found at all in the leanest individuals in this relatively large group and the
      cardiac size adjusted for body size indicated hypertrophy with increasing
      adiposity. Prospective autopsy studies are needed in order to determine whether
      adiposity and the regional distribution of fat, especially intra-abdominal fat
      accumulation, are associated with the earliest signs of myocardial hypertrophy
      and the initial phase of lesion development in the arterial intima of children.

PMID- 15481771
TI  - Muscle amino acid pattern in obese rats.
AB  - OBJECTIVE: To determine how the ability of skeletal muscle to manage amino acids
      is conditioned by obesity. The test was performed in two different models of
      obese rats: diet-obese rats and genetically obese rats. SUBJECTS: Lean and
      genetically obese (fa/fa) male Zucker rats were used. DESIGN: For up to 60 d of
      life lean animals were fed with standard chow pellet or with a hypercaloric
      cafeteria diet. Genetically obese rats were fed with standard chow pellet during
      the same period. MEASUREMENTS: Amino acid concentration in the femoral artery and
      vein and leg blood flow were measured. Free amino acid concentration, protein and
      nitrogen content and enzyme activities were determined in whole leg muscle.
      RESULTS: Amino acid availability was increased in diet-obese animals and remained
      unchanged in the genetically obese group. The genetically obese groups had a
      lower protein content and unchanged concentration of amino acids in leg muscle.
      Furthermore, total nitrogen remained unchanged in these animals and they showed
      an increased activity in alanine aminotransferase and glutamine synthetase. The
      leg muscle of the diet-obese rats took up several amino acids (Ala, Arg and Val)
      or released others (mainly Gln and Gly). Conversely, genetically obese rats took
      up many amino acids and did not release any. CONCLUSIONS: We conclude that in
      nutritionally obese rats there is an increased availability of amino acids in
      skeletal muscle. This augmented availability propitiates the increase in the
      uptake of many amino acids. In genetically obese rats, the lack of variation in
      amino acid availability points to a possible hereditary alteration that increases
      the capacity of different amino acid transport systems. Furthermore, the
      diminished protein content of fa/fa muscle is not due to a lower availability and
      intracellular pool of amino acids.

PMID- 15481772
TI  - Reduced plasma concentrations of transforming growth factor beta1 (TGF-beta1) in
      obese women.
AB  - OBJECTIVE: To evaluate Transforming Growth Factor beta1, (TGF-beta1) plasma
      concentrations and the possible relationship between this growth factor and
      various hormones in obese women. DESIGN: Case-control study. SETTING:
      Outpatient's Service for the Prevention and Treatment of Obesity at the
      University Hospital. SUBJECTS: Twenty-five women with mild to moderate obesity,
      and 15 non-obese healthy women were used as controls. MEASUREMENTS: Evaluation of
      TGF-beta1, insulin, prolactin, sex-hormone binding globulin, androstenedione,
      free triiodothyronine, free tetraiodothyronine, thyroid-stimulating hormone,
      dehydroepiandrosterone-sulfate, testosterone, insulin-like growth factor 1,
      cortisol and adrenocorticotropic hormone plasma concentrations in obese women.
      Blood samples were taken from fasting subjects for the determination of the above
      parameters. RESULTS: In obese women plasma TGF-beta1 concentrations were lower
      than in controls. The obese subjects also had lower GH, IGF-1 and SHBG plasma
      concentrations and increased insulinaemia. A positive correlation was found
      between TGF-beta1 and both IGF-1 (r = 0.52; P < 0.01) and DHEA-S (r = 0.43; P <
      0.05), while a negative correlation was found between TGF-beta1 and SHBG (r = 
      0.49; P < 0.05). CONCLUSIONS: The reduction in TGF-beta1, an antilipogenic
      factor, may play a role in the pathogenesis of obesity and could be involved in
      the development of some obesity-related endocrine alterations.

PMID- 15481773
TI  - Leptin and the hypothalamic-pituitary-adrenal axis activity in women with
      different obesity phenotypes.
AB  - OBJECTIVE: Women with visceral obesity may have hyperactivity of the hypothalamic
      pituitary-adrenal (HPA) axis. Since glucocorticoids are involved in the
      expression of the ob gene, this study was carried out to investigate the
      relationship between serum leptin and the activity of the HPA axis in women with
      different obesity phenotypes. DESIGN: Cross sectional clinical study. SUBJECTS:
      Fifteen obese (Body Mass Index BM128 kg/m2) women and ten normal weight control
      women (BM126 kg/m2) were included in the study. MEASUREMENTS: Body fat
      distribution was defined by CT scan at the L4-L5 level. Baseline blood samples
      were obtained for hormone concentrations. The activity of the HPA axis was
      evaluated by measuring ACTH and cortisol blood levels after combined iv
      administration of corticotropin releasing factor (100 microg) + arginine
      vasopressin (0.3 IU). RESULTS: Baseline cortisol, ACTH, and androgen levels were
      similar in all groups, whereas leptin levels were significantly higher in the
      obese groups than in normal weight controls, without any significant difference
      between women with different obesity phenotypes. Incremental areas of ACTH and
      cortisol were significantly higher in women with visceral obesity than in those
      with subcutaneous obesity and controls. No significant correlation was found
      between the activity of the HPA axis and leptin concentrations. Leptin showed a
      highly significant correlation with BMI and subcutaneous fat and a weak but
      significant correlation with visceral fat and the visceral-to-subcutaneous fat
      ratio. CONCLUSION: Women with different obesity phenotypes had similar serum
      leptin concentrations but different HPA axis activity, and there was no
      correlation between them.

PMID- 15481774
TI  - Continued increase in prevalence of obesity in Danish young men.
AB  - BACKGROUND: Previous studies of Danish young men showed a steep increase of
      obesity since the birth years of the early 1940s with a levelling off in the
      1950s. OBJECTIVE: To study the current prevalence of obesity and its recent
      changes in Danish young men. DESIGN: Cross-sectional study based on weight and
      height measured at the military board for the birth cohorts 1955, 1965 and 1973
      75. SUBJECTS: We obtained information from the old paper files comprising the two
      cohorts of men born in 1955 (6549 adults) and 1965 (6404 adults) and
      prospectively examined 4300 from the birth cohorts 1973-75 in a conscription
      district in Denmark during the period 1 August 1993 to 31 July 1994. RESULTS: The
      prevalence of obesity (defined as body mass index (BMI) > or = 30 kg/m2) was 1.5%
      in 1955, 2.1% in 1965 and 4.6% in 1973-75 birth cohorts. The median BMI has
      increased during the period from 21.7-22.8 kg/m2. CONCLUSION: Obesity is
      relatively common and has increased among Danish young men.

PMID- 15481775
TI  - Exploring the role of family in occupation and family occupations.

PMID- 15481776
TI  - A dialogue on occupational therapy, culture, and families.
AB  - This paper, based on a broad body of relevant data, presents a dialogue that
      explores and integrates two important concepts: family and culture. An
      understanding of these concepts is important for enhancing occupational therapy
      practice, in particular a practice that claims to be client-centered and
      holistic. The dialogue focuses particularly on issues students involved in the
      Intercultural Interaction Project, The University of Sydney, Australia, in 2002
      identified as important. These include: a lack of understanding of the concept of
      culture, the confounding of culture and ethnicity, considering culture as an
      issue only in families from "other" cultural backgrounds, assumptions about the
      nature of families and therapists' points of reference for making these
      assumptions, differences in client or family and therapist expectations, and how
      these expectations affect what happens in therapy and participants' level of
      satisfaction with the outcomes of the interactions involved. The information
      suggests that there is a need for a better understanding of how culture
      influences ideas about families and how to work with them.

PMID- 15481777
TI  - Family routines and rituals: a context for occupational therapy interventions.
AB  - PURPOSE: This paper explores the importance of family daily routines and rituals
      for the family's functioning and sense of identity. METHODS: The findings of this
      paper are derived from an analysis of the morning routines of 40 families with
      children with disabilities in the United States and Canada. The participants
      lived in urban and rural areas. Forty of the 49 participants were mothers and the
      majority of the families were of European descent. Between one and four
      interviews were conducted with each participant. Topics included the family's
      story, daily routines, and particular occupations. Data on the morning routines
      of the families were analyzed for order and affective and symbolic meaning using
      a narrative approach. FINDINGS: The findings are presented as narratives of
      morning activities in five families. These narratives are examples for rituals,
      routines, and the absence of a routine. Rituals are discussed in terms of their
      affective and symbolic qualities, routines are discussed in terms of the order
      they give to family life, whereas the lack of family routine is discussed in
      terms of lack of order in the family. CONCLUSIONS: Family routines and rituals
      are organizational and meaning systems that may affect family's ability to adapt
      them.

PMID- 15481778
TI  - Parent stress in the neonatal intensive care unit and the influence of parent and
      infant characteristics.
AB  - OBJECTIVE: This study investigated the stress experienced by parents in the
      neonatal intensive care unit (NICU), the infant and parent characteristics that
      resulted in different stress responses, and the characteristics that were
      predictive of stress. METHOD: The Parental Stress Scale: Neonatal Intensive Care
      Unit was used to measure the stress of 162 parents. A Parent/Infant Demographic
      sheet provided information for determining which characteristics resulted in
      different responses and which variables were stress predictors. RESULTS: The
      highest levels of stress experienced were in the relationship with baby-parental
      role area, and regarding how the baby looked and behaved. The infant
      characteristic of gestational age resulted in significantly different scores
      concerning the baby's appearance and behavior. Consistent predictors of stress
      were length of stay, extreme prematurity, and a cardiovascular diagnosis.
      CONCLUSION: Identifying the stressors parents experience can assist NICU
      therapists in intervention planning. Family-centered care that addresses
      stressors concerning their roles and their understanding of their infant should
      be emphasized.

PMID- 15481779
TI  - Mucho camino: the experiences of two undocumented Mexican mothers participating
      in their child's early intervention program.
AB  - OBJECTIVE: This study describes the experiences of two mothers of Mexican origin
      who are immigrants living under undocumented status in the United States and who
      participated in their children's early intervention programs. METHOD: In-depth
      interviews, archival data, and participant observation conducted with two mothers
      of children with special needs provided data for this case study design research.
      A phenomenological analytical approach and qualitative data analysis software
      were employed to gain understandings particular to each family's experience.
      RESULTS: These families share similar experiences and interactions with many
      other families in the United States who live within the context of having a child
      with a disabling condition. Constraints on family functioning related to the
      families' status of undocumented immigration included: mothers as active
      participants in their children's early intervention programs, mothers'
      understanding of their children, mothers' communication with service providers,
      and life as an immigrant family of Mexican origin living under undocumented
      status. CONCLUSIONS: The examination of how these mothers negotiated family life
      while participating in their child's early intervention program provides an
      appreciation for how these families view the long road--"mucho camino"--involved
      in achieving their family's well-being.

PMID- 15481780
TI  - The meaning of family routines in a homeless shelter.
AB  - OBJECTIVE: This exploratory investigation sought to understand what meaning
      parents, living in a homeless shelter, attribute to family routines and the
      nature of those routines. METHOD: In-depth interviews were conducted with 12
      parents living in a homeless shelter. Thematic analysis was employed to develop
      descriptive codes and themes from transcribed data and field notes. RESULTS:
      Parents described family routines focused on three features: promoting intimacy,
      maintaining or developing a legacy, and connections with the community. These
      routines seemed to preserve family integrity while homeless and to provide hope
      for the family to continue into the future. CONCLUSIONS: Homeless parents, in
      this investigation, seemed to expend a substantial amount of energy to create or
      maintain family routines while living in a homeless shelter. Findings suggest
      that occupational therapy services may help support homeless parents as they
      exercise their role as the organizer of family routines.

PMID- 15481781
TI  - The everyday occupation of families with children with autism.
AB  - The purpose of this qualitative research study was to understand a family's
      experiences negotiating family daily life and the meanings they ascribed to these
      experiences when they had a child with severe autism. In-depth, semistructured
      interviews were conducted with five family units. The interviews explored the
      meaning of the family's participation in daily life activities. The transcribed
      interviews were analyzed with a phenomenological method. The results emerging
      from this study indicate that families with children with severe autism may
      experience difficulty engaging in daily activities that hold positive meaning and
      rely on stringent patterns of routines that revolve around the child with autism
      to meet the demands of daily life.

PMID- 15481782
TI  - Parenting a child with a chronic medical condition.
AB  - PURPOSE: Parents of children with chronic medical conditions and associated
      disabilities have substantial caregiving responsibilities different from those of
      typical children. This ethnographic study examined how parents manage these
      caregiving demands, how they maintain their social lives, and how they form their
      self identities. METHOD: Graduate students interviewed eight parents of children
      with chronic medical conditions and disabilities and participated in 60 hours of
      activities with them over a 6-month time period. The interview transcripts,
      students' field notes, and journals were analyzed for themes that related to
      caregiving, social activities, and self-identity. RESULTS: Parents felt that they
      "always needed to be with their child," and most had changed their career plans
      to devote more time to caregiving. Parents also expressed anxiety about making
      difficult medical and educational decisions for their children. Activities
      outside the home required extensive planning and preparation and maintaining a
      social life was perceived as challenging because friends and relatives did not
      always understand the families' limitations in activity. CONCLUSIONS: Although
      the parents expressed stress related to coping with the caregiving load, they
      viewed having a child with chronic medical conditions as a positive experience
      that brought cohesion to their family. The parents explained that their
      experiences with their children helped them to appreciate life and develop more
      sensitivity to and tolerance of individual differences. The parents had become
      strong advocates for their children and other children with similar needs.

PMID- 15481783
TI  - Improving quality of life for persons with Alzheimer's disease and their family
      caregivers: brief occupational therapy intervention.
AB  - OBJECTIVE: This study examined the extent to which adherence to occupational
      therapy recommendations would increase the quality of life of persons with
      Alzheimer's disease living in the community and decrease the burden felt by
      family members caring for them. METHOD: Using a pretest-posttest control group
      design, the Assessment of Instrumental Function (AIF) was administered to two
      groups of persons with Alzheimer's disease in their own homes (n= 40). Caregivers
      completed measures of their feelings of burden and the quality of life, including
      level of function of the persons with Alzheimer's disease. RESULTS: A significant
      (MANCOVA) main effect was obtained for caregiver burden and three components of
      quality of life, positive affect, activity frequency and self-care status, by the
      treatment group, F(4, 31) = 7.34, p < .001. CONCLUSIONS: Individualized
      occupational therapy intervention based on the person-environment fit model
      appears effective for both caregivers and clients. This is especially important
      in light of a recent directive for more favorable reimbursement for occupational
      therapy services for persons with dementia.

PMID- 15481784
TI  - An evidence-based and occupational perspective of interventions for persons with
      substance-use disorders.
AB  - An interdisciplinary evidence-based review of interventions among persons with
      substance-use disorders was completed in 2001 as part of American Occupational
      Therapy Association's (AOTA's) Evidence-Based Literature Review Project
      (Lieberman & Scheer, 2002). Four effective interventions for adults and
      adolescents with substance use were identified, including brief interventions,
      cognitive behavioral therapy, motivational strategies, and 12-step programs. The
      research studies reviewed reported outcomes primarily related to reduction in
      alcohol and drug use. Occupational therapy interventions grounded in current
      evidence-based literature are suggested. Interventions are modified to include an
      occupational perspective leading to outcomes consistent with the Occupational
      Therapy Practice Framework (American Occupational Therapy Association [AOTA],
      2002). Study findings propose research questions to encourage further
      investigation of the effectiveness of these best practice interventions.

PMID- 15481785
TI  - A pilot study to investigate shoulder muscle fatigue during a sustained isometric
      wheelchair-propulsion effort using surface EMG.
AB  - OBJECTIVE: The primary aim of this pilot study was to develop a testing protocol
      for gathering shoulder muscle surface electromyography (EMG) data during a
      sustained submaximal isometric wheelchair-propulsion effort. Of special interest
      was analysis of the median frequency of the surface EMG signal power spectrum; a
      negative median frequency shift during a sustained effort is an indicator of
      muscle fatigue. The long-term goal is to improve our understanding of how fatigue
      and muscle imbalance might play a role in the development of a broad array of
      upper-extremity overuse syndromes. METHOD: Participants were a convenience sample
      of seven male manual-wheelchair users with spinal cord injury and 14 able-bodied
      males. Surface EMG in six right-side shoulder muscles was recorded while subjects
      resisted a static force equal to 60% of their maximum wheelchair-propulsion
      strength until fatigued. Percent of maximum voluntary contraction and the median
      frequency shift for each muscle were analyzed. RESULTS: The able-bodied group
      used a higher percent of maximum than the manual-wheelchair group (p< .05), and a
      more pronounced negative median frequency shift was evident in the able-bodied
      group (p < .10). CONCLUSION: Patterns that emerged suggest that spectral analysis
      of the surface electromyographhic signal has promise as a clinically useful tool
      to authenticate muscle fatigue in the upper extremities during occupational
      performance. Such data in the future could be used to justify the need for and
      benefits of adapted performance techniques and assistive technology.

PMID- 15481786
TI  - Bottom-up or top-down evaluation: is one better than the other?

PMID- 15481787
TI  - Protective effects of N-n-butyl haloperidol iodide on myocardial ischemia
      reperfusion injury in rabbits.
AB  - N-n-butyl haloperidol iodide (F2), a novel compound derived from haloperidol, was
      synthesized by our drugs research lab. The present study aims to evaluate the
      protective effects of F2 on myocardial ischemia-reperfusion injury in vivo, and
      to try to find the protective mechanism of F2. The animal model of myocardial
      ischemia-reperfusion injury was established by ligaturing rabbit's left
      ventricular branch of coronary artery for 40 min and removing the ligation later
      to reperfuse for 40 min. Different doses of F2 were intravenously injected before
      the onset of ischemia. The changes of hemodynamics were recorded during the
      experiment, and the activities of superoxide dismutase (SOD), creatine kinase
      (CK), Ca2+-ATPase, Na+,K+-ATPase and the level of malondialdehyde (MDA) of
      myocardial tissue were detected after reperfusion. Administration of F2 could
      dose-dependently ameliorate the hemodynamics of ischemia-reperfusion injured
      myocardium. During the course of reperfusion, MAP, LVSP, +/-dP/dt(max) in all F2
      groups were obviously higher than those in the ischemia-reperfusion control
      group, and LVEDP were lower. F2 could also reduce the production of MDA, and
      maintain the activities of SOD, Ca2+-ATPase, Na+,K+-ATPase, and minimize the
      leakage of CK out of myocardial cells in a dose-dependent manner. These results
      suggested that F2 had apparent protective effects against myocardial ischemia
      reperfusion injury.

PMID- 15481788
TI  - Effects of 17beta-estradiol and phytoestrogen alpha-zearalanol on tissue factor
      in plasma of ovariectomized rats and HUVECs.
AB  - In the present study, the effects of 17beta-estradiol (E2) and phytoestrogen
      alpha-zearalanol (ZAL) on tissue factor (TF) in plasma of ovariectomized (OVX)
      rats and human umbilical vein endothelial cells (HUVECs) were investigated. OVX
      rats were injected intramuscularly twice a week with E2 (1mg/kg) or ZAL (1mg/kg)
      for five weeks. The concentrations of plasma E2 were measured by
      radioimmunoassay. The TF levels of plasma were assayed by enzyme-linked
      immunosorbent assay (ELISA). HUVECs were exposed to E2 or ZAL for 48 h. TF
      protein and mRNA were assayed by ELISA and RT-PCR, respectively. Nuclear proteins
      of HUVECs opposed to E2 or ZAL for 8 h were extracted to assay transcription
      factors activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) by
      Western blot. Both E2 and ZAL were found to decrease plasma TF levels of OVX rats
      significantly. E2 or ZAL were also found down-regulate the expression of TF
      protein and mRNA in HUVECs. Moreover, both E2 and ZAL might decrease AP-1 and NF
      kappaB levels. These results suggest that both E2 and ZAL have inhibitory effects
      on TF in plasma of OVX rats and HUVECs, which may then contribute to their
      protective effects on cardiovascular diseases.

PMID- 15481789
TI  - Augmented release of matrix metalloproteinase-9 by PKC activation in organotypic
      cultures of human breast cancer and adjacent normal breast tissue and
      fibroadenoma.
AB  - The organotypic culture technique and quantitative gelatin zymography were used
      to determine the expression of matrix metalloproteinase (MMP)-9 and MMP-2 in
      human breast cancer and adjacent normal breast tissue and fibroadenoma. MMP-9 and
      MMP2 were constitutively expressed in all cultures. The release of these two
      enzymes in breast cancer was higher than that in adjacent normal breast tissue
      and fibroadenoma. Administration of 12-o-tetradecanoyl- phorbol-13-acetate (TPA)
      increased the release of MMP-9 but not of MMP-2. This response was inhibited by
      protein kinase C (PKC) inhibitor (H7), transcription inhibitor (actinomycin D)
      and translation inhibitor (cycloheximide). Moreover, the increased level of MMP-9
      by TPA in breast cancer was also higher than that in adjacent normal breast
      tissue and fibroadenoma. These phenomena were also observed in the DAG-treated
      culture. These findings suggested that the MMP-9 expression in the breast cancer
      tissue may be more sensitive for the PKC activation.

PMID- 15481790
TI  - IgA immune complex blunts the contraction of cultured mesangial cells through the
      inhibition of protein kinase C and intracellular calcium.
AB  - The effects of IgA immune complex (IgA-IC) on the contractile function of
      cultured mesangial cells were measured by the changes in planar surface area in
      response to treatment with agonists. Incubation of mesangial cells with IgA-IC
      for 24 hours significantly decreased the contractile responses to angiotensin II
      (10(-6) M) and phorbol 12-myristate 13-acetate (PMA, 10(-6) M). Pretreatment of
      mesangial cells with the protein kinase C (PKC) inhibitor, chelerythrine (10(-6)
      M), eliminated the difference in contractile responses to angiotensin II or PMA
      between the control and IgA-IC groups indicating IgA-IC may inhibit the activity
      of PKC. The contractile responses to ionomycin were not significantly different
      between IgA-IC treated and control mesangial cells, suggesting that the
      contractile machinery is not impaired by IgA-IC. Intracellular calcium, [Ca2+]i
      measured by changes in fura-2 level in response to ATP or bradykinin, was
      significantly inhibited in IgA-IC treated mesangial cells, compared to control
      cells. In contrast, treatment with thapsigargin did not result in significant
      differences in [Ca2+]i between IgA-IC and control mesangial cells, suggesting
      that a negligible role of endoplasmic reticulum in the effects of IgA-IC. Using
      PKC specific antibodies, IgA-IC significantly increased the particulate fraction
      of PKC-iota of mesangial cells to 141+/-13% of control, without significantly
      changing the protein content of PKC-alpha, -delta and -lambda in the cytosolic
      and particulate fractions. In summary, IgA-IC inhibits the contractile responses
      of cultured mesangial cells to agonists by inhibiting the activation of PKC and
      [Ca2+]i.

PMID- 15481791
TI  - Arecoline excites the colonic smooth muscle motility via M3 receptor in rabbits.
AB  - Arecoline is an effective component of areca (betel nuts, a Chinese medicine
      named pinang or binglang). The purpose of this study was to investigate the
      effect of arecoline on the motility of distal colon in rabbits and its mechanisms
      involved. Strips of colonic smooth muscle were suspended in organ baths
      containing Krebs solution, and their isometric contractions were examined. The
      response of smooth muscle to arecoline in colonic strips was recorded. The
      effects of atropine, gallamine and 1,1-dimethyl-4
      diphenylacetoxypiperidiniumiodide (4-DAMP) on arecoline-induced contraction were
      also observed. Arecoline (1 nM - 1 microM) produced a concentration-dependent
      contraction in both the longitudinal and the circular smooth muscle of rabbit
      colon. Atropine (10 microM) abolished the arecoline (80 nM)--induced contraction.
      M3 receptor antagonist, 4 - DAMP (0.4 microM), abolished the arecoline (80 nM)-
      related response, whereas M2 receptor antagonist, gallamine (0.4 microM), did not
      affect the effect of arecoline. These results suggest that arecoline excites the
      colonic motility via M3 receptor in rabbits.

PMID- 15481792
TI  - Horseradish peroxidase localization of sympathetic postganglionic and
      parasympathetic preganglionic neurons innervating the monkey heart.
AB  - The localization of the sympathetic postganglionic and parasympathetic
      preganglionic neurons innervating the monkey heart were investigated through
      retrograde axonal transport with horseradish peroxidase (HRP). HRP (4 mg or 30
      mg) was injected into the subepicardial and myocardial layers in four different
      cardiac regions. The animals were euthanized 84-96 hours later and fixed by
      paraformaldehyde perfusion via the left ventricle. The brain stem and the
      paravertebral sympathetic ganglia from the superior cervical, middle cervical,
      and stellate ganglia down to the T9 ganglia were removed and processed for HRP
      identification. Following injection of HRP into the apex of the heart, the
      sinoatrial nodal region, or the right ventricle, HRP-labeled sympathetic neurons
      were found exclusively in the right superior cervical ganglion (64.8%) or in the
      left superior cervical ganglion (35%). Fewer labeled cells were found in the
      right stellate ganglia. After HRP injection into the left ventricle, labeled
      sympathetic cells were found chiefly in the left superior cervical ganglion (51%)
      or in the right superior cervical ganglion (38.6%); a few labeled cells were seen
      in the stellate ganglion bilaterally and in the left middle cervical ganglion.
      Also, in response to administration of HRP into the anterior part of the apex,
      anterior middle part of the right ventricle, posterior upper part of the left
      ventricle, or sinoatrial nodal region, HRP-labeled parasympathetic neurons were
      found in the nucleus ambiguus on both the right (74.8%) and left (25.2%) sides.
      No HRP-labeled cells were found in the dorsal motor nucleus of the vagus on
      either side.

PMID- 15481793
TI  - [An infrequent cause of choledochus syndrome].

PMID- 15481794
TI  - [An infrequent neoplasia with multiple synonyms].

PMID- 15481795
TI  - [Percutaneous management of benign pathology of the main biliary tract:
      experience in a section of pancreatic and hepatobiliary surgery].
AB  - BACKGROUND: Biliary percutaneous procedures (BPP) are useful on management of
      benign biliary pathology. OBJECTIVE: Communicate our experience with percutaneous
      biliary procedures made by surgeons in a specific Hepato-Pancreato-Biliary
      Section. POPULATION: Retrospective evaluation in 84 patients with benign biliary
      diseases, treated with BPP from January 1989 through January 2002. RESULTS:
      Diagnosis common bile duct stones 21 patients, strictures after common bile duct
      injury (SCBDI) 29 patients, and other benign bile duct strictures (OBBDS) 34
      patients. INDICATIONS: Acute cholangitis 45, pruritus 11, high surgical risk 10,
      contraindicated or failed endoscopic access 9, before liver transplantation 12
      and other causes 3. Procedures (n=141): percutaneous drainage 96, stricture
      dilatation 27, percutaneous stone treatment 12, stents 5 and biopsy 1.
      EFFECTIVENESS: Cholangitis 94.8%, stones 100%, anastomotic stricture dilatation
      (by SCBDI 45.5% and by OBBDS 90%). COMPLICATIONS: Total 32 (38.1%). MORTALITY: 3
      (3.6%). CONCLUSIONS: 1-Percutaneous drainage was an effective method for bile
      duct decompression in acute cholangitis, allowing an elective and definitive
      treatment of the pathology. 2-BPP solved strictures in patients with a high
      surgical risk and in those with complex diseases. 3-The results of biliary
      percutaneous dilatation were related to their etiology.

PMID- 15481796
TI  - [Epidemiologic study of Helicobacter pylori infection in Peru].
AB  - We present the results of our investigations in the epidemiology of H. pylori
      infection in Peru during the last two decades. The prevalence of Helicobacter
      pylori infection in Lima is decreasing in people of middle and high socioeconomic
      status and continues stationary in people of low socioeconomic status. This
      decrease is similar in Peruvian and Japanese population in this city, and is
      associated to the decrease of the gastrointestinal diseases related to this
      bacterium: peptic ulcer and stomach adenocarcinoma. The infection is slightly
      greater in males and is acquired in early ages of life. Via oro-fecal and water
      contamination are probably the most important transmission ways. In our country,
      so far, there is no evidence to assure that some races have higher pre
      disposition to acquire the infection. There are no differences in the infection
      by H. pylori among coast, mountain or jungle populations; and people who live in
      high altitudes have more atrophic chronic gastritis secondary to H. pylori
      infection than people who live at sea level.

PMID- 15481797
TI  - [Lymphoepithelioma-like gastric carcinoma: unusual variant in postgastrectomy
      stump].
AB  - Gastric lymphoepithelioma--like carcinoma, undifferentiated with lymphoid or
      medullary stroma, constitutes a 3.8% of gastric carcinomas. Microscopically it is
      similar to other lymphoepitheliomas, it has an expansive growth and better
      prognosis than other histologic types. A possible relation to Epstein Barr virus
      is presumed. A 56 year old female, gastrectomized due to a cancer (Billroth II)
      31 years before, showed an ulcer lesion close to the anastomosis at endoscopy. A
      biopsy was taken with positive result and gastrectomy was performed. The surgical
      specimen included gastric stump, jejunoanastomosis, omentum and lymph nodes. It
      had a 4.5 cm, protruded ulcerated lesion, located in anterior wall, 1.5 cm from
      stomy. It was fixed in buffered formalin, routinely processed and stained with
      Hematoxilin--Eosin. Immunohistochemistry techniques for CKAE1-AE3, EMA, CEA,
      CD45, CD20, CD3 and CD45Ro, and PCR for Epstein Barr virus were performed.
      Microscopically it was constituted by an expansive proliferation of polygonal
      cells with barely eosinophylic cytoplasm and vesicular nuclei, arranged in small
      clusters or isolated, positive for CKAE1-AE3, EMA and CEA, with dense mature
      lymphoid infiltrate, both follicular and diffuse, positive for CD45, CD45Ro, CD3
      and CD20. PCR technique for Epstein Barr virus was positive. This has been the
      first case of this type in our department since 1989. In addition to the peculiar
      characteristics of this variety, whose differential diagnosis must be made with
      lymphomas, the origin from gastric stump, where this complication appears with
      variable rates, the risk being related to the type of surgery and the time
      elapsed are relevant.

PMID- 15481798
TI  - [Clinical manifestations and late complications of the hepatic hydatid cyst:
      report of 4 cases].
AB  - INTRODUCTION: Hepatic hydatid cyst (HHC) may appear and remain free of symptoms
      for a long time, require treatment of its syptoms or relapse after an adequate
      treatment. The HHC relapse after a medical and surgical treatment is considered a
      complication of the disease as well as the infection, breakup or other
      complications. OBJECTIVES: Describe four patients with HHC whose complication or
      relapse symptoms appeared between 13 and 26 years after the disease was known or
      adequately treated. CASE REPORT: Four patients with previously diagnosed HHC and
      symptoms associated to its relapse or infection were retrospectively studied.
      Patient 1: woman, 48 years old, with diagnosis of HHC during a cholecistectomy in
      1977, who showed a touchable mass in 1998. Patient 2: woman, 45 years old, with
      HHC surgery in 1973, who referred pain and HHC relapse in 1996. Patient 3: woman,
      43 years old, with HHC diagnosed in 1980, who referred abdominal pain with
      increase of HHC volume in 1996. Patient 4: man, 60 years old, with HHC diagnosed
      in 1981, who referred fever in 1996 related to an abscess of the HHC. The four
      patients presented HHC relapse and symptoms due to its complications. Medical and
      surgical treatment was needed in all the cases. CONCLUSIONS: We observed that HHC
      disease may present complications many years after its surgical treatment with
      late symptomatic relapses and that the non-treated disease may also develop
      complications many years after remaining asymptomatic.

PMID- 15481799
TI  - [Acute variceal bleeding].

PMID- 15481800
TI  - Does computation provide a model for creativity? An epistemological perspective
      in neuroscience.
AB  - In 1939 Alan Turing, a major scholar in the field of mechanical computation,
      described a system whose computational power was beyond that of a discrete,
      finite state machine (Turing Machine). The composition of this system was likely
      the first example of what is now called an hybrid computational system. Since
      then, development of neural networks and brain automata has made aware that forms
      of computation might exist that are likely to go beyond Turing's limits. Natural
      systems, like the central nervous system in Mammals and man, are likely to use
      such a type of computation, especially to perform highly integrating activities,
      like feedback controls and mental creative processes. The latter are usually
      understood as processes that involve infinitary procedures, ending up in a
      complex information network, the computational maps, in which both digital,
      Turing-like computation and continuous, analog forms of calculus are expected to
      occur. Pictorial representation may be a fruitful example, mostly metaphorical,
      to analyze the use of this hybrid forms of computation by higher order
      computational maps, and the possible role of these types of computational
      processes in painting creativity is briefly analyzed in comparing 15th vs 16th
      century Renaissance Art. An open challenge for neuroscience in the 21st century
      is to clarify whether a hybrid neural learning network might represent a
      reasonable clue to scientifically interpret the theme of "creativity".

PMID- 15481801
TI  - Energy gradients for VT-signal migration in the CNS: studies on melanocortin
      receptors, mitochondrial uncoupling proteins and food intake.
AB  - The present paper enlightens a new point of view on brain homeostasis and
      communication, namely how the brain takes advantage of different chemical
      physical phenomena such as pressure waves, and temperature and concentration
      gradients to allow the homeostasis of the brain internal milieu as well as some
      forms of intercellular communications (volume transmission, VT) at an energy cost
      much lower than the classical synaptic transmission (the prototype of wiring
      transmission, WT). The possible melanocortin control of uncoupling protein 2
      (UCP2) expression (hence of local brain temperature gradients) has been studied
      in relation to food intake in male Wistar rats. Osmotic minipumps were
      subcutaneously (sc) implanted in the midscapular region for
      intracerebroventricular (icv) infusion. The control rats received an icv infusion
      of 0.5 microl/h of artificial cerebrospinal fluid (ACSF), while experimental rats
      received either an icv infusion of 0.16 nmol/h of HS024 or of 0.16 nmol/h of
      adrenocorticotropin-(1-24) [ACTH-(1-24)]. The ACTH-treated group ate
      significantly less than the ACSF-treated group during the first three days of
      infusion, while, subsequently, food intake of the two groups was similar. On the
      other hand, the HS024-treated group ate significantly more (up to 153% of the
      control value) than ACSF- and ACTH-treated rats during the entire period. UCP2
      mRNA analysis in arcuate nuclei of ACTH, HS024 and ACSF-treated animals showed a
      significant 75% decrease (p<0.05 vs saline) of the total specific mRNA level in
      the HS024-treated group vs ACSF-treated animals (control group), while no
      significant change was observed between ACTH- and ACSF-treated animals.
      Melanocortin antagonist HS024 via blockade of MCR4 increases food intake and via
      a reduction of UCP2 expression enhances the food consumption ratio. This result
      underlines the fact that UCP2 expression and food intake can be differentially
      regulated. In other words, via a peptidergic control the central nervous system
      (CNS) can modulate the energy stored from the amount of the food that the animal
      has eaten and also uncouple the thermal micro-gradients (dependent on UCP2
      expression) and hence the VT-signal micro-migrations from the food intake. It
      should also be noticed that the control of the thermal gradients affects also the
      neuronal firing rate and hence the transmitter release (likely above all the
      release of peptides such as neuropeptide Y (NPY), melanin-concentrating hormone
      (MCH) and beta-endorphin, e.g., in the arcuate nucleus representing signals
      relevant to energy homeostasis). Thus, WT and VT are both modulated by
      peptidergic signals that affect thermal gradients.

PMID- 15481802
TI  - The neuroendocrine system: organization and homeostatic role.
AB  - The neuroendocrine system (NES) of Vertebrates can be defined as a set of cells
      organized in single organs and diffuse elements, sharing co-production of amine
      hormone/transmitters, peptide hormone/transmitters and specific markers of neural
      determination. In this perspective, the hypothalamic-pituitary-target organ axis
      (H-P axis), the autonomic nervous system (ANS) and the diffuse neuroendocrine or
      APUD system contribute to the NES. However, in Mammals and man virtually any
      compartment of the body harbors elements, often with different embryologic
      origin, having at least some of the NES features. Thus, all anatomical structures
      may be part of a wide functional circuitry, based on "internal secretions", that
      supersedes the current view of the NES. Historically, metaphysical antecedents of
      this concept can be found in the biomedical tradition dealing with the idea of
      the so called "vital energy". Currently, the "internal secretions" circuitry can
      be envisaged as an informational supersystem encompassing the H-P axis, ANS,
      APUD, immune and any other body system performing autocrine, paracrine and/or
      endocrine regulations, that superintends the homeostatic balance. Evolutionary
      evidence shows that diffuse autocrine/paracrine/endocrine, peptidergic secretions
      would be the oldest and hierachically simplest signals, with respect to the later
      and hierarchically more complex ANS and H-P axis outputs, to regulate body
      homeostasis. Therefore, the new acronym "Triune Information Network" (TIN) is
      proposed for the informational supersystem of internal secretions acting in
      Mammals and man via progressively higher levels of control (diffuse
      autocrine/paracrine/endocrine secretions, ANS and H-P axis) on a common energetic
      substrate: the internal body milieu.

PMID- 15481803
TI  - Neuroendocrinology of acute immunity.
AB  - Bacterial endotoxins such as Escherichia coli lipopolysaccharide (LPS) bind to
      specific Toll-like receptors in fixed and circulating immunocompetent cells and
      activate the sympathetic and pituitary-adrenal system through similar receptors
      in cells that form the blood-brain interface. The latter, in turn, lead to the
      formation, within the brain, of proinflammatory cytokines including interleukin
      (IL)-1alpha, IL-1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), and one or
      more antinflammatory cytokines including tumor growth factor beta (TGF-beta), and
      IL-10. Although the full panoply of central cytokines can be activated after
      systemic exposure, direct introduction of IL-1beta into the brain exerts a unique
      pattern of peripheral immune responses attributable to the special properties of
      reactive cells within the brain and to the "reservoir" function of the
      cerebrospinal fluid compartment. De Simoni et al. were the first to show that the
      intracerebroventricular (icv) injection of IL-1beta in rats induced a dramatic
      increase in the concentration of circulating IL-6 that was much greater and more
      prolonged than that induced by intravenous bolus injection of the same dose of
      cytokine. The work reported in this paper shows that the "De Simoni paradox" is
      mainly due to the prolonged release of the injected IL-1beta from brain to blood:
      a large proportion is not degraded (86%), transport out is both active and
      passive, and the initial exposure to IL-1beta sensitizes peripheral responses to
      the continuing exposure to the cytokine. Although IL-6, TNF-alpha and LPS are
      passively transferred from brain to blood (as shown by radioiodine-labeled tracer
      studies) peripheral cytokine responses to central injection differ from responses
      to IL-1beta. Peripheral responses to central TNF-alpha are similar to those after
      peripheral administration because TNF-alpha has no peripheral sensitizing effect.
      Peripheral response to central LPS exposure is much less than that which occurs
      when an amount identical with that transferred from brain to blood is
      administered peripherally. This is due to the fact that intracerebral injection
      of LPS suppresses response to peripherally administered endotoxin. Since the
      effect can still be demonstrated in adrenalectomized animals maintained on a
      constant dose of corticosterone, the brain has the capacity by as yet undefined
      mechanisms to suppress peripheral inflammatory responses.

PMID- 15481804
TI  - Neuroendocrine hypothesis of aging: the role of corticoadrenal steroids.
AB  - The age-related modifications of neuroendocrine secretions normally capable of
      integrative activity in the whole body might partly promote and amplify many
      aging phenomena. The quantitative and qualitative changes of hypothalamus
      pituitary-adrenal axis are a significant example. The dampening of cortisol and
      dehydroepiandrosterone (DHEA) circadian fluctuation and the progressive decrease
      of DHEA/cortisol ratio are at the basis of multiple clinical implications: the
      shift from anabolic to catabolic status, the activation of atherosclerosis
      progression, the deterioration of immune competence, the impairment of cognitive
      and affective performances and the glico- and lipometabolic disorders. The
      hypothesis of a DHEA supplementation strategy comes out from these premises.

PMID- 15481805
TI  - Neural stem cells: an overview.
AB  - Multipotent stem cells are present in the majority of mammalian tissues where
      they are a renewable source of specialized cells. According to the several
      biological portions from which multipotent stem cells can be derived, they are
      characterized as a) embryonic stem cells (ESCs) isolated from the pluripotent
      inner-cell mass of the pre-implantation blastocyste-stage embryo; b) multipotent
      fetal stem cells (FSCs) from aborted fetuses; and c) adult stem cells (ASCs)
      localized in small zones of several organs known as "niche" where a subset of
      tissue cells and extracellular substrates can indefinitely house one or more stem
      cells and control their self-renewal and progeny production in vivo. ECSs have an
      high self-renewing capacity, plasticity and pluripotency over the years.
      Pluripotency is a property that makes a stem cell able to give rise to all cell
      type found in the embryo and adult animals.

PMID- 15481806
TI  - "Ultrashort" control of hypothalamic hormones secretion: a brief history.
AB  - Some 30 years ago we proposed that the synthesis of the hypothalamic releasing
      factors (RFs) might be influenced by changes of their own titers in the general
      circulation and in the hypothalamus. At that time the dominating concept was that
      there were two different hypothalamic RFs controling respectively follicle
      stimulating hormone (FSHRF) and luteinizing hormone (LHRF). The possible
      existence of the first "ultrashort" feedback system was proposed on the basis of
      the observation that in male rats castrated, to eliminate the "long" feedback
      effect of testosterone, and then hypophysectomized, to abolish the possible
      "short" feedback effect of pituitary hormones on the hypothalamus, the
      intrahypothalamic levels of FSHRF resulted to be higher than in controls.
      Following a treatment with an hypothalamic extract, the intrahypothalamic stores
      of FSHRF returned to pre-operation levels, suggesting that a factor present in
      the hypothalamic extract might exert an inhibitory influence on the synthesis of
      FSHRF. In 1987, we confirmed these findings using an in vitro perfusion system of
      rat hypothalamic tissue, where the amount of gonadotropin-releasing hormone
      (GnRH) released was measured in the effluent. When a GnRH analog was added to the
      perfusion medium, both the spontaneous and the stimulated release of GnRH were
      totally obliterated. The presence of specific binding sites for GnRH has been
      clearly demonstrated in GnRH neurons. It is becoming consequently attractive the
      hypothesis that paracrine interactions might occur among GnRH neurons,
      entertaining an "ultrashort" feedback control of GnRH secretion.

PMID- 15481807
TI  - The human hypothalamus: a morpho-functional perspective.
AB  - Historical investigation suggests that the role of the hypothalamus as a site of
      integration for endocrine with autonomic and behavioral responses in man rises
      from ideas and observations first appearing between the 14th and 18th centuries.
      Research on human, post-mortem brains and by in vivo magnetic resonance
      techniques reveal that the functional morphology of the hypothalamus in man is
      very similar to that in Rodents and Primates. As such, the adult human
      hypothalamus can be subdivided in three longitudinal zones, representing the
      source and target of neural informations traveling back and forth the brain stem,
      thalamus, limbic system, basal ganglia and neocortex. In addition, the human
      hypothalamus can be further partitioned in three anterior-posterior regions, of
      which the rostral one exerts a prominent regulation in predictive homeostasis, as
      opposed to the two caudal ones, primarily involved in reactive homeostasis.
      Finally, nuclear distribution in the human hypothalamus largely coincides with
      that in higher Mammals. Nevertheless, it is still unclear how the hypothalamus
      may give rise to specific homeostatic behaviors like hunger, thirst, reproductive
      and parental attitude, thermoregulation, aggressive-defensive performance,
      affective-motivational tone, circadian rhythmicity, sleep-wake cycle and immune
      regulation. The recent advent of new theories for nervous communication, like
      volume transmission and neural Darwinism, is progressively enlightening our
      understanding of the role played by the hypothalamic architecture in homeostatic
      responses, both in Mammals and man.

PMID- 15481808
TI  - Role of proopiomelanocortin neurons and peptides in the regulation of energy
      homeostasis.
AB  - The purpose of this brief review is to highlight recent studies from our
      laboratory and collaborators based on the analysis of novel strains of mutant
      mice that further our understanding of the complex regulatory roles of
      proopiomelanocortin (POMC) neurons and POMC peptides in energy homeostasis. Mouse
      models that are considered include a transgenic strain with expression of
      enhanced green fluorescent protein in POMC neurons, facilitating analyses of the
      cell intrinsic membrane and synaptic properties, and two gene knockout strains
      exhibiting either a selective absence of beta-endorphin production or a complete
      loss of all POMC peptides from the pituitary gland and nervous system. Together
      these studies demonstrate the wide variety of hormonal, metabolic, and
      transsynaptic signals that converge on the arcuate hypothalamic nucleus and
      nucleus tractus solitarius to regulate the activity of POMC neurons. Both
      melanocortin peptides and the opioid beta-endorphin processed from POMC mediate
      the homeostatic and behavioral responses linked to POMC neuronal circuits.

PMID- 15481809
TI  - Ghrelin: more than a new frontier in neuroendocrinology.
AB  - Ghrelin, a peptide predominantly produced by the stomach, has been discovered as
      natural ligand of the growth hormone secretagogue receptor (GHS-R) type 1a. More
      recently, ghrelin attracted enormous interest as new orexigenic factor. However,
      ghrelin exerts several other neuroendocrine, metabolic and also non-endocrine
      actions (e.g. cardiovascular activities) that are explained by the widespread
      distribution of ghrelin and GHS-R expression. The existence of GHS-R subtypes and
      evidence that neuroendocrine but not all other ghrelin actions are dependent on
      acylation in serine 3 add further complexity to the system whose major
      physiological role remains to be definitely clarified. What we are learning from
      the studies about the control of ghrelin secretion is that it is mostly under
      metabolic control; the most important impact of ghrelin would, in turn, be
      metabolic. However, a recent study states that the ghrelin knockout (KO) mouse is
      not anorectic dwarf and this evidence clearly depicts a remarkable difference
      from the leptin KO mouse. Nevertheless, the original and fascinating ghrelin
      story as well as its potential pathophysiological implications in endocrinology
      and internal medicine are not definitely canceled by this evidence. Besides
      potential clinical implications for natural or synthetic ghrelin analogues acting
      as agonists or antagonists, open questions that are waiting for an answer are:
      how many are the ghrelin receptors? Is ghrelin the or a GHS ligand, i.e. are
      there other natural GHS-R ligands? Is there a functional balance between acylated
      and unacylated ghrelin forms that would play different actions? Within the next
      years these questions will find the appropriate answer and we'll know about the
      ghrelin system something more precise; this knowledge will more appropriately
      clarify the potential clinical perspectives.

PMID- 15481810
TI  - Feedback regulation of thyrotropin-releasing hormone (TRH): mechanisms for the
      non-thyroidal illness syndrome.
AB  - Regulation of the hypothalamic-pituitary-thyroid (HPT) axis is dependent upon the
      secretion of thyrotropin-releasing hormone (TRH), a tripeptide originating in the
      hypothalamic paraventricular nucleus (PVN). These so-called hypophysiotropic
      neurons are under feedback inhibition by circulating levels of thyroid hormone,
      mediated through interactions with the beta2 thyroid hormone receptor (TRbeta2)
      and competition with the phosphorylated form of cyclic adenosine 5'-monophosphate
      response element binding protein (CREB) for a multifunctional binding site in the
      TRH gene. The non-thyroidal illness syndrome, characterized by low circulating
      thyroid hormone levels yet suppression of TRH gene expression in hypophysiotropic
      neurons, is due to alteration in the regulatory factors that modulate TRH gene
      expression to result in central hypothyroidism. These factors include alpha
      melanocyte-stimulating hormone (alphaMSH) and cocaine- and amphetamine-regulated
      transcript (CART), and agouti-related protein (AGRP) and neuropeptide Y (NPY),
      substances co-produced by distinct populations of leptin-responsive neurons in
      the hypothalamic arcuate nucleus. Through monosynaptic projections from arcuate
      nucleus neurons to hypophysiotropic TRH neurons, these factors contribute to
      suppression of HPT axis during fasting and starvation by exerting opposing
      actions on the TRH gene, altering the sensitivity for feedback inhibition by
      thyroid hormone. In contrast, central hypothyroidism associated with infection
      may be due to upregulation of type 2 deiodinase activity in tanycytes,
      specialized glial cells that line the infralateral walls and floor of the third
      ventricle. Through tanycyte-cerebrospinal fluid, -vascular or -neuronal
      associations, these cells may lead to inhibition of TRH gene expression in
      hypophysiotropic neurons by increasing local triiodothyronine production.

PMID- 15481811
TI  - Sexual differentiation of the brain: role of testosterone and its active
      metabolites.
AB  - The sex-related morphological differences of many brain nuclei are mainly
      determined by the hormonal environment present during embryonic development.
      These morphological differences are at the basis of the gender-specific secretion
      of many hypothalamic and pituitary hormones, of sexual and aggressive behavior,
      etc. It is known that, at least in rodents, testosterone (T) secreted by the
      fetal testes plays a key role in the permanent organization of the developing
      central nervous system (CNS) toward masculine patterns. The main aspect
      concerning the mechanism of action of T is that the brain, and especially the
      hypothalamus, possesses the enzymes that transforms this hormone into compounds
      which amplify (dihydrotestosterone) or differentiate (estrogens) its action;
      these enzymatic systems are the 5alpha-reductase and the aromatase respectively.
      In this short review are summarized the main results obtained in our and other
      laboratories concerning some characteristics of the two enzymatic pathways in the
      developing CNS and the possible dimorphism in their expression during
      ontogenesis. On the basis of diseases in which alterations of the normal levels
      and/or of the mechanism of action of gonadal hormones during embryogenesis are
      present, in the last part of the paper some hypotheses on the possible influence
      of T metabolites in the sexual differentiation of the human brain are also drawn.

PMID- 15481812
TI  - Kinetics of neuronal and endocrine secretion.
AB  - Calcium (Ca2+) regulated secretion/exocytosis is a key mechanism for cell-cell
      communication. Neurotransmission and hormone release are the most studied and the
      best characterized of all secretion systems so far. Here, some dynamic aspects of
      secretory vesicle trafficking will be briefly reviewed with special emphasis on
      the differences between synaptic vesicle and dense-core vesicle turnover.

PMID- 15481813
TI  - The ambivalent nature of the calcium signal.
AB  - In the couse of evolution, calcium has emerged as the most versatile
      intracellular messenger. Its concentration within cells is controlled by
      reversible binding to specific protein acting as sensors to decode its
      information. The decoding operation is based on specific conformational changes
      in these sensor proteins. Other proteins intrinsic to membranes (plasma membrane,
      endosarcoplasmic reticulum, mitochondria, nuclear envelope) simply control
      calcium concentration by transporting it across membrane boundaries. Calcium is
      an ambivalent signaling agent. It carries information to all processes important
      to cell life, including excitation-contraction coupling, secretion, gene
      transcription and enzyme activity through protein phosphorylation
      dephosphorylation. However, it also transmits signals that promote programmed
      demise of cells and, when escaping control, it may also precipitate toxic cell
      death.

PMID- 15481814
TI  - Phosphatidylinositol phosphate kinases.
AB  - Phosphatidylinositol 4,5-bisphosphate is a multi-functional lipid, whose proposed
      functions now number more than twenty, covering many aspects of cell biology in
      several different subcellular compartments. The enzymes primarily responsible for
      synthesizing this lipid, the Type I phosphatidylinositol 4-phosphate 5-kinases,
      are therefore a tightly regulated and diverse family. Here we review our current
      knowledge about these enzymes and how they may be regulated.

PMID- 15481815
TI  - Significance of nuclear phospholipase C signaling through type 1 IGF receptor.
AB  - The existence of a nuclear polyphosphoinositol metabolism independent from that
      at the plasma membrane is now widely recognized. Specific changes in the nuclear
      phosphatidylinositol (Ptdlns) metabolism have been implicated in cell growth,
      differentiation, and neoplastic transformation. Here we shall review the main
      features of nuclear inositol lipid signaling through type I IGF receptor,
      focusing the attention on the role of inositide-specific phospholipase C (PI-PLC)
      beta1 in cell proliferation and differentiation, given its peculiar localization
      in the nuclear compartment.

PMID- 15481816
TI  - The response of human natural killer cells to interleukin-2.
AB  - Natural killer cells play a key role in the defence of organisms against virus
      infections and in the control of tumor onset. Interleukin-2 is a multifunctional
      inflammatory cytokine able to activate natural killer cells, essentially inducing
      cell proliferation, lymphokine-activated-killer cell generation and cytokine
      production. Here we discuss some signaling events generated by interleukin-2 in
      the cell nucleus of primary human natural killer cells, specifically focusing on
      the lipid signal transduction and the induction of the cyclic adenosine-5'
      monophosphate response element binding protein transcription factor. The
      implications of these nuclear events in the response of natural killer cells to
      interleukin-2 are also discussed.

PMID- 15481817
TI  - Molecular mechanisms for pituitary thyrotroph cell growth.
AB  - Neuroendocrine, endocrine and autocrine/paracrine signals contribute to the
      regulation of basal thyrotroph growth. Thyrotropin-releasing hormone (TRH),
      somatostatin, thyroid hormone (TH), estrogens (Es) and epidermal growth factor,
      all may play a role both in normal and tumoral thyrotroph proliferation, acting
      via either plasma membrane receptors and non-genomic steps or nuclear receptors
      and gene transcription. Signaling features common to all these ligands are
      involvement of G protein-coupled receptors, mitogen-activated protein kinase
      cascade and nuclear polyphosphoinositide cycle. In addition, each growth
      information, independently from the eliciting factor, may be routed
      intracellularly following a branched pathway, that often links different
      transduction systems at common check-points, as the Shc-Grb2-SOS complex.
      Finally, some ligands (e.g. TRH, TH, Es) may display opposite effects on
      thyrotroph growth, depending on environmental conditions and state of cell
      differentiation. These ambiguities of response can be interpreted using a "fuzzy"
      logic-based model of intracellular signaling. Accordingly, check-points common to
      different transduction cascades may be envisaged as targets for antitumoral
      therapy selective to the neoplastic thyrotroph cell.

PMID- 15481818
TI  - Somatostatin signal transduction in thyroid parafollicular C cells.
AB  - The effects of somatostatin (SRIF) through its receptors (SSTRs) has been
      explored in many tissues, and here we discuss the role of the SRIF-SSTR system in
      human parafollicular C cells, reporting recent data on the effects of selective
      SSTR agonists on parafollicular C cells, that suggest new therapeutic approaches
      for medical treatment of medullary thyroid carcinoma. Moreover, the possible
      pathways involved in SRIF signalling in parafollicular C cells are discussed.

PMID- 15481819
TI  - Metabotropic receptors as targets for drugs of potential use in the treatment of
      neuropathic pain.
AB  - Glutamate is the major neurotransmitter in the mammalian central nervous system
      and plays a pivotal role in both acute and chronic pain. The actions of glutamate
      are mediated by two receptor families: ionotropic glutamate receptors (iGluRs),
      and metabotropic glutamate receptors (mGluRs). Activation of glutamate receptor
      can elicit both hyperalgesic and analgesic effects. Eight mGluRs subtypes (mGluR1
      mGluR8) have been identified and classified into three groups. Among these, group
      I mGluRs (mGlu1 and -5) have been implicated in the processes of central
      sensitization and persistent nociception, whereas activation of group II mGluRs
      (mGlu2/3) is effective against neuropathic or inflammatory pain. In this review
      we focus on the role of mGlu2/3 in the modulation of persistent pain, and on
      their potential use as drug targets in pain management.

PMID- 15481820
TI  - Small fibers peroneal mononeuropathy in a patient with Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is an autoimmune epithelitis characterized by lymphocytic
      infiltration of exocrine glands and epithelia in multiple sites. One third of the
      patients present with peripheral nervous system involvement. We describe the case
      of a woman aged 62 affected by a peroneal nerve mononeuropathy with painful
      disturbances secondary to a prevalent involvement of small fibers as demonstrated
      by electrophysiological investigations and skin biopsy. Asymmetric peripheral
      nerve involvement is not uncommon in SS, though, to our knowledge, it has never
      been reported of a mononeuropathy involving primarily small fibers.

PMID- 15481821
TI  - Comparative analysis of neonicotinoid binding to insect membranes: I. A structure
      activity study of the mode of [3H]imidacloprid displacement in Myzus persicae and
      Aphis craccivora.
AB  - Neonicotinoids bind selectively to insect nicotinic acetylcholine receptors with
      nanomolar affinity to act as potent insecticides. While the members of the
      neonicotinoid class have many structural features in common, it is not known
      whether they also share the same mode of binding to the target receptor. Previous
      competition studies with [3H]imidacloprid, the first commercialised
      neonicotinoid, indicated that thiamethoxam, representing a novel structural sub
      class, may bind in a different way from that of other neonicotinoids. In the
      present work we analysed the mode of [3H]imidacloprid displacement by established
      neonicotinoids and newly synthesized analogues in the aphids Myzus persicae
      Sulzer and Aphis craccivora Koch. We found two classes of neonicotinoids with
      distinct modes of interference with [3H]imidacloprid, described as direct
      competitive inhibition and non-competitive inhibition, respectively. Competitive
      neonicotinoids were acetamiprid, nitenpyram, thiacloprid, clothianidin and
      nithiazine, whereas thiamethoxam and the N-methyl analogues of imidacloprid and
      clothianidin showed non-competitive inhibition. The chloropyridine or
      chlorothiazole heterocycles, the polar pharmacophore parts, such as nitroimino,
      cyanoimino and nitromethylene, and the cyclic or acyclic structure of the
      pharmacophore were not relevant for the mode of inhibition. Consensus structural
      features of the neonicotinoids were defined for the two mechanisms of interaction
      with [3H]imidacloprid binding. Furthermore, two sub-classes of non-competitive
      inhibitors can be discriminated on the basis of their Hill coefficients for
      imidacloprid displacement. We conclude from the present data that the direct
      competitors share the binding site with imidacloprid, whereas non-competitive
      compounds, like thiamethoxam, bind to a different site or in a different mode.

PMID- 15481822
TI  - Comparative analysis of neonicotinoid binding to insect membranes: II. An unusual
      high affinity site for [3H]thiamethoxam in Myzus persicae and Aphis craccivora.
AB  - Neonicotinoids represent a class of insect-selective ligands of nicotinic
      acetylcholine receptors. Imidacloprid, the first commercially used neonicotinoid
      insecticide, has been studied on neuronal preparations from many insects to date.
      Here we report first intrinsic binding data of thiamethoxam, using membranes from
      Myzus persicae Sulzer and Aphis craccivora Koch. In both aphids, specific binding
      of [3H]thiamethoxam was sensitive to temperature, while the absolute level of non
      specific binding was not affected. In M persicae, binding capacity (Bmax) for
      [3H]thiamethoxam was ca 450 fmol mg(-1) of protein at 22 degrees C and ca 700
      fmol mg(-1) of protein at 2 degrees C. The negative effect of increased
      temperature was reversible and hence not due to some destructive process. The
      affinity for [3H]thiamethoxam was less affected by temperature: Kd was ca 11 nM
      at 2 degrees C and ca 15 nM at 22 degrees C. The membranes also lost binding
      sites for [3H]thiamethoxam during prolonged storage at room temperature, and upon
      freezing and thawing. In A craccivora, [3H]thiamethoxam was bound with a capacity
      of ca 1000 fmol mg(-1) protein and an affinity of ca 90 nM, as measured at 2
      degrees C. Overall, the in vitro temperature sensitivity of [3H]thiamethoxam
      binding was in obvious contrast to the behaviour of [3H]imidacloprid studied in
      parallel. Moreover, the binding of [3H]thiamethoxam was inhibited by imidacloprid
      in a non-competitive mode, as shown with M persicae. In our view, these
      differences demonstrate that thiamethoxam and imidacloprid, which represent
      different structural sub-classes of neonicotinoids, do not share the same binding
      site or mode. This holds also for other neonicotinoids, as we report in a
      companion article.

PMID- 15481823
TI  - Influence of dispersion length on leaching calculated with PEARL, PELMO and PRZM
      for FOCUS groundwater scenarios.
AB  - Harmonisation of the assessment of pesticide leaching to groundwater for EU
      registration is desirable to minimise confusion in the decision-making process at
      EU level. Recently, the FOCUS groundwater scenarios have been developed for three
      chromatographic models (PEARL, PELMO and PRZM) to increase this harmonisation.
      This study investigates the role of dispersion parameterisation in explaining the
      cause of the differences in pesticide leaching calculated by these models. PEARL
      describes dispersion via a physical parameter, ie the dispersion length. PELMO
      and PRZM simulate dispersion via a numerical procedure which generates an
      effective dispersion length equal to 0.5 times the thickness of the numerical
      compartments. The hypothesis was tested that the difference in the dispersion
      length input parameter (ie 5 cm for PEARL and about 2.5 cm for PELMO and PRZM) is
      a major cause of the difference in calculated leaching. It was tested whether
      results of PEARL calculations with a dispersion length of 2.5 cm corresponded
      much better to results of PELMO or PRZM than results of PEARL calculations with a
      dispersion length of 5 cm. This was done by calculations for one substance and
      all nine FOCUS scenarios and by calculations for a range of substances and two
      FOCUS scenarios (Chateaudun and Sevilla). All calculations were for winter wheat
      and an application at 1 day before emergence. Both tests showed that reduction of
      the dispersion length from 5 to 2.5 cm in PEARL led to a much better
      correspondence between PEARL and either PELMO or PRZM. Hence the hypothesis was
      supported. It is likely that harmonisation of the dispersion length in the FOCUS
      groundwater scenarios would reduce the differences in calculated leaching between
      PEARL and PELMO or PRZM considerably for part of these scenarios.

PMID- 15481824
TI  - Synthesis and herbicidal activity of new oxazinone herbicides with a long-lasting
      herbicidal activity against Echinochloa oryzicola.
AB  - Chemical modification of the herbicide 1-[2-(benzothiazol-2-yl)isopropyl]-4
      methyl-3-phenyl-5H-pyrrolin-2-one (MI-2826) has revealed a new oxazinone
      herbicide, 3-[2-(7-chlorobenzothiazol-2-yl)isopropyl]-2,3-dihydro-6-methyl-5
      phenyl-4H-1,3-oxazin-4-one (MI-3069), for use in paddy fields. In comparing the
      phyototoxicity of the two herbicides to transplanted rice, the latter was
      superior to the former and kept the same predominant characteristic to control
      Echinochloa oryzicola Vasin for a long period of time owing to its long-lasting
      residual effect.

PMID- 15481825
TI  - Pesticide adsorption in the vadose zone: a case study on Eocene and Quaternary
      materials in Northern France.
AB  - We present a set of adsorption coefficients measured on various Eocene and
      Quaternary materials sampled from the vadose zone of a catchment in Northern
      France for three herbicides, atrazine, isoproturon and metamitron. Some vadose
      zone materials were found to have higher adsorption coefficients than the
      topsoil. The adsorption coefficients were strongly dependent on the clay content
      of the material. From 83% to 97% of the variability in the adsorption
      coefficients could be explained by a linear relationship to the clay content.
      Adsorption coefficients normalized for clay content, Kclay, ranged between 1.6
      and 17.6 litre kg(-1) for atrazine. Neglecting the adsorption properties of the
      vadose zone and relying exclusively on Koc values to predict mobility may bias
      regional or local risk assessment of groundwater contamination by pesticides.
      More information on the adsorption properties of geological materials should be
      collected to improve our ability to predict pesticide concentrations in
      groundwaters.

PMID- 15481826
TI  - Fenpyroximate resistance in Tetranychus urticae (Acari: Tetranychidae): cross
      resistance and biochemical resistance mechanisms.
AB  - A field colony of the Two-spotted spider mite, Tetranychus urticae (Koch),
      resistant to fenpyroximate was further selected with fenpyroximate 5SC for 20
      generations at a selection pressure of 30-50% mortality (designated as FR-20
      strain). Resistance and cross-resistance levels of the FR-20 strain to 18
      acaricides were determined using a spray method. The FR-20 strain was extremely
      resistant to fenpyroximate [resistance ratio (RR) 252]. The strain exhibited
      extremely strong positive cross-resistance to acrinathrin (RR 196), and high
      levels of resistance to benzoximate (RR 55) and propargite (RR 64). Moderate
      levels of cross-resistance (RR 11-40) to abamectin, fenbutatin oxide,
      fenpropathrin, pyridaben, pyridaben + bifenthrin and tebufenpyrad were observed.
      The FR-20 strain showed low levels of resistance (RR < 10) to azocyclotin,
      bromopropylate, chlorfenapyr, chlorfenapyr + bifenthrin, chlorfenapyr +
      pyridaben, dicofol, fenazaquin and milbemectin. Synergist experiments with
      different metabolic inhibitors revealed that piperonyl butoxide had the greatest
      effect on the efficacy of fenpyroximate, followed by iprobenfos and triphenyl
      phosphate. In a comparative assay with detoxifying enzymes, the FR-20 strain
      showed 2.5-fold higher activity in p-nitroanisole-O-demethylation, and 2.5- and
      2.2-fold higher activities in alpha- and beta-naphthyl acetate hydrolysis,
      respectively. These results suggested that enhanced activities of both mixed
      function oxidases and esterases likely contribute to the fenpyroximate resistance
      of the FR-20 strain of T urticae.

PMID- 15481827
TI  - Synthesis and fungicidal activity of ethaboxam against Oomycetes.
AB  - This study describes the chemical synthesis and intrinsic fungicidal activity of
      ethaboxam [(RS)-N-(alpha-cyano-2-thenyl)-4-ethyl-2-(ethylamino)-1,3-thiazole-5
      carboxamide], a new Oomycetes fungicide. In in vitro tests, ethaboxam showed
      inhibitory activity against isolates of Phytophthora and some Pythium spp, with
      MIC values ranging from 0.1 to 0.5 mg litre(-1) for nine isolates of Phytophthora
      infestans (Montagne) de Bary and from 1.0 to 5.0 mg litre(-1) for eight isolates
      of Phytophthora capsici Leonian. In tests to determine time and concentration for
      complete inactivation of each pathogen (five isolates of P infestans and five
      isolates of P capsici), ethaboxam inactivated all isolates of P infestans within
      48h at 10 mg litre(-1) and those of P capsici within 96 h at 10 mg litre(-1).
      Ethaboxam effectively suppressed development of tomato late blight caused by P
      infestans and pepper Phytophthora blight caused by P capsici in the studies
      conducted to determine its preventive, curative, persistent and systemic
      activity. These results show that ethaboxam has desirable fungicidal
      characteristics as an Oomycetes fungicide.

PMID- 15481828
TI  - Molecular characterization and inheritance of resistance to ACCase-inhibiting
      herbicides in Lolium rigidum.
AB  - The molecular basis and mode of inheritance of resistance to ACCase-inhibiting
      herbicides were investigated in a biotype of Lolium rigidum Gaud that has been
      discovered in Israel. Dose-response experiments at the whole-plant level have
      revealed that the resistant biotype was more resistant (6.3- to 40-fold) than the
      susceptible wild-type to ACCase-inhibiting herbicides. A 276-bp genomic DNA
      encoding the carboxyltransferase domain within the chloroplastic ACCase from
      resistant and susceptible biotypes were amplified by PCR and analyzed. Sequence
      comparison revealed that a single isoleucine-to-leucine substitution
      differentiated ACCases from susceptible and resistant biotypes (corresponds to
      residue 1769 of wheat ACCase, Acc No AF029895). A PCR amplification of specific
      alleles (PASA) method was developed to detect the allele composition leading to
      isoleucine-leucine mutation. ACCase extracted from homozygote resistant,
      heterozygote and homozygote susceptible plants showed IC50 values of 25.8, 5.6
      and 0.6 microM, respectively, suggesting that alteration in the ACCase is
      governed by a co-dominant gene. The inheritance studies confirmed that the
      resistance of L rigidum to ACCase-inhibiting herbicides is governed by a single,
      nuclear and co-dominant gene.

PMID- 15481829
TI  - Improving the persistence of a formulation of the avian repellent cinnamamide,
      for the protection of autumn-sown oilseed rape.
AB  - In a previous pilot field trial on autumn-sown oilseed rape (Brassica napus L), a
      suspension concentrate formulation of the avian repellent cinnamamide, using
      Acronal 4D (50 g litre(-1)) as the sticker, was shown to reduce damage by
      woodpigeons (Columba palumbus L). However, the persistence of cinnamamide on rape
      leaves was poor. This paper describes the development of a weather-resistant
      formulation by the inclusion of a more effective sticker. In vitro studies were
      used to investigate wash-off of cinnamamide, which was identified as being the
      major mechanism of loss in the field. Rainfastness of cinnamamide was assessed by
      washing deposits on glass slides and rape leaves using a 'rain-washing machine'.
      A number of stickers were evaluated and the effect of sticker concentration,
      ageing of deposits, freezing and intermittent washing on rain-fastness was
      investigated. None of the candidate stickers showed increased rainfastness
      compared to Acronal 4D. However, two of the stickers, Crovol T40 G and Emoleo L1,
      when combined with Acronal 4D in small amounts, did reduce wash-off compared with
      Acronal 4D alone. Freezing led to an increase in wash-off of cinnamamide, but
      inclusion of Emoleo L1 with Acronal 4D reduced this effect. Increasing the
      concentration of the sticker was also shown to improve the rainfastness; doubling
      the concentration of Acronal from 50 to 100 g litre(-1) halved the wash-off of
      cinnamamide.

PMID- 15481830
TI  - Integrated pest management approach for a new pest, Lacanobia subjuncta
      (Lepidoptera: Noctuidae), in Washington apple orchards.
AB  - Bioassays of Lacanobia subjuncta (Grote and Robinson) larvae established baseline
      LC50 values and identified the potential of reduced-risk, organophosphate
      replacement and naturally derived insecticides (eg chloronicotinyls, spinosyns,
      oxadiazines, insect growth regulators, microbial insecticides and particle films)
      to control this pest. The toxicities of these products were compared with those
      of organophosphate, carbamate, chlorinated cyclodiene and synthetic pyrethroid
      insecticides used in the management of lepidopteran pests in Washington apple
      orchards. Field trials were conducted comparing candidate insecticides to
      conventional alternatives. Several new insecticides (eg spinosad,
      methoxyfenozide, indoxacarb and an aluminosilicate particle film) proved to be
      effective for the management of L subjuncta. We summarize the goals and
      challenges of developing an integrated pest management program for new and
      resurgent pests as insecticide tools continue to change, and propose a hypothesis
      for the sudden increase in pest status of L subjuncta based on organophosphate
      tolerances. The role of novel insecticides with unique modes of action in
      resistance management and the encouragement of biological control are also
      discussed.

PMID- 15481831
TI  - Juvenogens as potential agents in termite control: laboratory screening.
AB  - Preliminary screening tests of eight juvenogens, fatty acid esters of two parent
      juvenoid alcohols, showed high juvenilizing effect in the termite Prorhinotermes
      simplex (Hagen). This effect is manifested by differentiation of termite workers
      into pre-soldiers, soldiers and/or soldier-intercastes ('soldiers'). Juvenogen 9
      was tested with five other termite species: Zootermopsis angusticollis Hagen,
      Kalotermes flavicollis F, Cryptotermes declivis Tsai & Chen, Reticulitermes
      santonensis de Feytaud, and R flaviceps Oshima, and showed promising efficacy in
      force-feeding (FF) as well as in choice bioassays. In the economically important
      subterranean termites R santonensis and R flaviceps, after application of 0.5 mg
      ml(-1) in FF experiments ca 57 and 73%, respectively, of workers changed into
      soldiers. In Zootermopsis angusticollis application of 0.05 mg ml(-1) caused
      differentiation in 62% soldiers, and 57% soldiers differentiated after topical
      application of 1 microg of the tested compound per termite. Differentiation of
      excessive soldiers induced by a juvenile hormone-mimicking compound may cause
      disruption of the social structure and ultimately the death of the colony.

PMID- 15481832
TI  - Growth and pathogenicity of isolates of the fungus Metarhizium anisopliae against
      the parasitic mite, Psoroptes ovis: effects of temperature and formulation.
AB  - Psoroptes mites (Acari: Psoroptidae) are important ectoparasites of mammals, and
      are of particular economic significance as the agents of mange in sheep. To be
      effective against mites, putative fungal biocontrol agents must be able to
      operate at the relatively high temperatures and humidities found at the sheep
      skin surface. To consider this, the growth rates of different isolates of the
      entomopathogenic fungus Metarhizium anisopliae (Metschnikoff) Sorokin
      (Deuteromycotina: Hyphomycetes) were compared and the pathogenicity of these
      isolates against Psoroptes derived from rabbits (Psoroptes ovis Hering, syn P
      cuniculi) were evaluated at temperatures between 28 degrees C and 40 degrees C,
      and when formulated in either Tween 80 or silicone oil. For this study four multi
      conidia, arthropod-derived, isolates of M anisopliae were used: from the USA,
      France, Denmark and Brazil. One single-conidia culture derived from the US
      isolate was also included in the investigation. Fungal growth was higher at the
      lower temperatures and none of the isolates grew at 40 degrees C. The growth of
      the US and single-conidia isolate declined markedly with temperature. In
      contrast, the Danish, French and Brazilian isolates grew almost as well at 32
      degrees C and 35 degrees C as at 28 degrees C and 30 degrees C. The French and
      Brazilian isolates showed some growth at 37.5 degrees C but the Danish and US
      isolates did not. The number of fatal infections which resulted from exposure of
      mites to the fungal isolates was also strongly influenced by temperature. At 30
      degrees C all isolates gave between 70 and 90% infection. The number of
      infections declined with increasing temperature and no infections were seen at 40
      degrees C. However, the French and Danish isolates of M anisopliae gave higher
      numbers of infections than the other isolates at elevated temperatures. When
      formulated in silicone oil, significantly higher levels of infection were
      obtained than when formulated in Tween 80, even at the relatively high
      temperature of 37.5 degrees C. It is suggested that high-temperature adapted
      isolates of M anisopliae formulated in silicone oil offer good candidates as
      control agents under the conditions found at the sheep skin surface.

PMID- 15481834
TI  - Bicarbonate action on early events in sperm activation.

PMID- 15481833
TI  - The role of cDermo-1 and cTwist in the avian embryo.

PMID- 15481835
TI  - Morphological study on the gills of two species of fresh water fishes:
      Oreochromis niloticus and Clarias gariepinus.
AB  - The gross and microscopic morphology of the gills of both Nile tilabia
      (Oreochromis niloticus) and sharptooth catfish (Clarias gariepinus) were
      described including light and scanning electron microscopy. The anatomical
      differences between the gill system of the two species were basically related to
      the geometry of the head and opercular cavities. Each species had four pairs of
      gills which were connected in a median interbranchial septum. In addition, a
      fifth rudimentary gill without gill filaments was found in catfish. The lengths
      and gaps between the gill arches in both species decreased medialwards. The gill
      rakers of tilabia were generally short and widely spaced compared to the long and
      narrow spaced rakers of the catfish. The gill filaments and lamellae of tilabia
      were longer than those of the catfish indicating a greater gill surface area in
      the former species. The catfish was additionally supplied by modified gills in
      the form of branched bulbous dendritic structures originating from the second and
      fourth gill arches. Scanning electron microscopy revealed that the surface of
      both gill filaments and lamellae was covered by polyhedral cells in tilabia and
      oval or elongated cells in catfish. These cells carried numerous microplicae
      which were better developed in tilabia. All gill parts, as revealed by light
      microscope, were nearly covered by mucous epithelium, however, the mucous cells
      were present on the lamellae of the catfish only. The rakers of both species
      demonstrated many taste buds and infiltrating lymphocytes in the epithelial
      covering. In catfish, in particular, several alarm substance cells were also
      scattered in this epithelium.

PMID- 15481836
TI  - [Congenital or acquired disposition of the separate compartment of the extensor
      pollicis brevis tendon associated with stenosing tendovaginitis (de Quervain's
      disease)? Macroanatomical and fetal-plastinationhistological studies of the first
      compartment of the wrist].
AB  - Our macroanatomical studies with cadaver specimens and clinical findings in the
      operative treatment of tendovaginitis stenosans de Quervain confirm the high
      number of anatomical variations in the first dorsal compartment of the wrist.
      With the help of thick transparent transversal-sections in one of 14 fetal wrists
      manufactured by plastination histology we found the first compartment with two
      tendons of the abductor pollicis longus and dorsal of this compartment a
      connective tissue formation and a separate compartment for the extensor pollicis
      brevis tendon, proved as a primary anatomical disposition. Macroscopically the
      septation is always located distal and dorsal-ulnar to the first compartment and
      is evidentally more common as an intraoperative than an cadaver dissection
      finding and probably should be considered as a pathological condition. The
      secondary formation of an incomplete until complete separate septum may depend on
      the multiple abductor pollicis longus tendons and on chronical inflammatory
      reaction of the synovialis of the constricted extensor pollicis brevis tendon.

PMID- 15481837
TI  - [Plastination-histological investigations on the inserting extensor pollicis
      brevis tendon on the proximal phalanx of the thumb].
AB  - By help of thick transparent cross-sections of 10 thumbs, manufactured by
      plastination histology, it has been shown that the most fibres of the extensor
      pollicis brevis tendon insert on a special tubercle of the basis of the proximal
      phalanx. Our studies prove that the shape of this tubercle is configurated in the
      phalanx proximalis longitudinally between the first and second fifth part and in
      the wideness of the base, seen from radial to ulnar between the forth and fifth
      tenth part.

PMID- 15481838
TI  - Computed tomographic assessment of the trachea in the German shepherd dog.
AB  - Computed tomographic (CT) examination of the trachea was performed in 10 German
      shepherd dogs to determine the normal value of some tracheal measurements under
      general anesthesia and in sternal recumbence position. Measurements obtained from
      nine segments were evaluated in four groups as the cranial cervical, caudal
      cervical, thoracic inlet and the thoracal tracheas. The inner transverse (T) and
      vertical (V) diameters were measured with the aid of electronic calipers from the
      software of the CT scanner. The cross-sectional lumen area (CSA) was calculated
      by using vertical and transverse diameters. The ratio of the transverse and
      vertical diameters (T/V) was also calculated. There was not any significant
      difference between thoracic inlet and thoracic tracheas, however, the mentioned
      regions were found to be significantly different from both cranial and caudal
      cervical regions in all measurements except the ratio of T/V. The ratio of T/V
      between 0.92 and 1.06 gradually changed and there was not any statistical
      difference between subsequent regions while differences were found among further
      regions. The largest CSA, seen in cranial cervical trachea was as 364.62 mm2 and
      decreased gradually to 309.29, 245.69 and 226.50 mm2 in caudal cervical, thoracic
      inlet and thoracic tracheas, respectively. From the point of view of technique,
      CT examination of the dog trachea was very easy and it was possible to take
      sensitive and repeated measurements. It, however, may be accepted as expensive
      and that it is disadvantageous to require general anesthesia. The data presented
      in this study represent tracheal values in the healthy German shepherd dog under
      the conditions of the study.

PMID- 15481839
TI  - Correlation analysis of the skull and long bone measurements of the dog.
AB  - In this study, a heterogeneous population of 42 dogs was examined for correlation
      between skull and long bone measurements. For this purpose, 17 craniometric
      measurements were carried out and used to calculate 12 indices and ratios. These
      indices and ratios were then subjected to a correlation analysis with long bone
      measurements. While a high significant negative correlation of p < 0.05 and p <
      0.01 respectively was found for skull, cranial and facial I1, I2, LLI-2, BI and
      BI-1 indices, and the CFO and CFO-1 ratios respectively with respect to the non
      indexed long bone measurements, a high positive correlation was found to exist
      between those indices and ratios, and the long bone indices (p < 0.01). The
      correlation coefficients for the skull indices and ratios to long bone
      measurements proved to be very similar for the long bones of front and hind legs.
      As a result of the correlation analysis, it was found that with an increase in
      skull tendency towards the dolichocephalic type, the long bone parameters also
      increase, while with the skull tending towards the brachycephalic type, the long
      bone parameters decrease. This finding of a long bone-related increase in
      dimensions and morphological skull expression favours the assumption of a close
      relation to the skull typology.

PMID- 15481841
TI  - Comparative histology of lymph nodes from aged animals and humans with special
      reference to the proportional areas of the nodal cortex and sinus.
AB  - Lymph nodes are composed of a lymphocyte-rich area or cortex (subdivided into the
      superficial and deep cortex and the medullary cord) and another, macrophage-rich
      area (incorporating the subcapsular and medullary sinuses). We measured the
      proportional area of the cortex in lymph nodes from aged experimental mammals
      (rats, guinea pigs, dogs and rabbits) and elderly Japanese humans. The cervical,
      axillary and inguinal nodes were generally richer in cortex tissue than the
      pulmonary regional and mesenteric nodes. Histological heterogeneity and medullary
      sinus dominance were much more evident in the human nodes than in those from
      animals, except for the guinea pig thoracic node. Human pulmonary regional nodes
      were characterized by a large medullary sinus; in guinea pigs, these nodes had a
      similar histology but the T lymphocyte-containing areas were smaller and thinner
      than in humans. The paraaortic node was well developed in humans and dogs, but
      not in other animals tested. These species- and region-specific histological
      differences may influence the evaluation of experimental animal models of lymph
      node function, such as those recently identified for research into sentinel
      nodes.

PMID- 15481840
TI  - Bone remodeling analysis of various dental implant surfaces using
      polyfluorochrome sequential labeling in rabbit tibias.
AB  - The purpose of this study is to analyze the bone remodeling process after the
      placement of threaded implants with rough (RBM) and hydroxyapatite coated
      surfaces (HA) in rabbit tibias using polyfluorochrome sequential labeling.
      Histomorphometry was performed in order to quantify the amount of each label
      deposited during the healing period. This work demonstrates the possibility of
      periodic identification of apatite deposition during bone remodeling around
      titanium and ceramic implants. It has been concluded that the polyfluorochrome
      sequential labeling is an important tool for identification of bone remodeling
      after the insertion of titanium and ceramic implants inside rabbit tibias.

PMID- 15481842
TI  - Origin of the primary efferent neurons projecting to the prostate of the dog.
AB  - The retrograde tracing technique of neuronal tracer Fast Blue was used to
      determine sources of origin of efferent nerve fibers supplying the prostate of
      the dog. After injection of Fast Blue into the canine prostate retrogradely
      labelled neurons were found in bilateral L3-S3 sympathetic chain ganglia,
      bilateral caudal mesenteric ganglion and in bilateral pelvic plexus ganglia. No
      Fast Blue-positive neurons were present in bilateral L1-L2 sympathetic chain
      ganglia and in coeliac-mesenteric ganglion complex. The vast majority of Fast
      Blue-positive efferent prostate-projecting neurons (56.2% +/- 1.7) were located
      in bilateral caudal mesenteric ganglion, whereas 28.7% +/- 1.5 of them were
      located in bilateral pelvic plexus ganglia and 14.9% +/- 0.5 in bilateral L3-S3
      sympathetic chain ganglia. Immunohistochemical staining for tyrosine hydroxylase
      and dopamine beta-hydroxylase was applied to determine the neurochemical
      character of Fast Blue-positive efferent neurons. Immunohistochemistry revealed
      that in all tyrosine hydroxylase immunoreactive Fast Blue-positive neurons
      immunoreactivity for dopamine beta-hydroxylase was also found (noradrenergic
      neurons) while all tyrosine hydroxylase-negative Fast Blue-positive neurons did
      not express dopamine beta-hydroxylase (non-noradrenergic neurons). In bilateral
      sympathetic chain ganglia, 96.4% +/- 2.1 of the prostate-projecting neurons were
      adrenergic and in bilateral caudal mesenteric ganglion this frequency amounted to
      95.6% +/- 1.6. In bilateral pelvic plexus ganglia, 26.7% +/- 1.5 of the prostate
      supplying efferent neurons did not express either tyrosine hydroxylase or
      dopamine beta-hydroxylase immunoreactivity which makes discussion of their
      cholinergic character possible.

PMID- 15481843
TI  - Branching projection of the nucleus "k" neurons to the rabbit cerebellar
      paramedian lobule: a retrograde fluorescent tracing study.
AB  - The nucleus "k", in the reticular core of the rabbit caudal pons, is divided into
      a large medial (composed of dorsal k1 and ventral k2) and a small lateral (k3)
      subdivision. In this study, the nucleus "k" subdivisions were examined in the
      rabbit with respect to projections to the cortex of rostral (rPML; face-forelimb
      region) and caudal (cPML; hindlimb region) paramedian lobule of the cerebellum.
      The retrograde fluorescent labeling method with Fast Blue (FB) and Diamidino
      Yellow (DY) was used. Numerous single FB or DY labeled neurons were found in
      defined regions of all nucleus "k" subdivisions bilaterally, with an ipsilateral
      preponderance. The distribution of these neurons indicated that afferents
      originating from different nucleus "k" subdivisions terminated in overlapping
      regions within the rPML and the cPML rather than in separate domains. Apart from
      this, double FB + DY labeled neurons (n = 104) were intermingled within a common
      region of single labeling, but exclusively on the ipsilateral side. Such neurons
      occupied predominantly the central and lateral regions of the caudal two thirds
      of the k1 subdivision, and were scattered in the caudal half of k2 as well as
      throughout the entire rostrocaudal extent of the k3 subdivision. The size of
      labeled perikarya varied from 20 to 40 microm in diameter. The number of neurons
      with branching axons was considerably lower than those with single projections to
      the rPML and the cPML. It amounted to about 3% in k1 and k3, and 2% in the k2
      subdivision. However, this population may form an intralobular link between two
      somatotopically non-corresponding PML regions. The present study provides a
      morphological basis for further investigations for comparison with other species
      using both anatomical and electrophysiological methods, also with respect to
      other connections of the nucleus "k".

PMID- 15481844
TI  - Metric sexual dimorphism in the deciduous teeth of Old World monkeys.
AB  - Metric variability of the deciduous teeth of several Old World monkey taxa were
      examined at the intergeneric and interspecific taxonomic levels. In general, the
      deciduous teeth of these taxa lack significant size sexual dimorphism with the
      exception of Papio cynocephalus. The data clearly demonstrate that male
      dimensions are not consistently larger than those of the females, in fact, female
      dimensions are frequently larger than those of the male. Thus, negative
      percentage sexual dimorphism is present in all species except Papio cynocephalus.
      Tooth size differences are randomly distributed among these species and do not
      appear to have any anatomical significance with respect to the different diets of
      the colobine and cercopithecine monkeys. This odontometric analysis reveals that
      it would be problematical to use deciduous tooth size as a basis for species
      identification with the possible exception of Papio cynocephalus.

PMID- 15481845
TI  - [Multiple variations of the hand arteries (short communication)].
AB  - A human hand was injected with red-coloured gelatine. There, three varieties in
      the arterious blood supply were detected. (1) The radial artery directly ramifies
      to branches for the forefinger and the middle finger, (2) The radial artery
      divides an the dorsum manus, (3) A branch from the superficial palmar arc
      contributes to the supply of the thumb.

PMID- 15481846
TI  - Ultrastructural localization of hyaluronic acid in the synovium of the goat knee
      joint.
AB  - In the Japanese miniature (Shiba) goat, the synovial membrane contains
      synoviocytes referred to as type A (macrophage-like cells) and type B cells
      (fibroblast-like cells) in the intimal layer. Small capillaries and blood vessels
      of varying sizes were located in the extracellular matrix in the synovial
      subintima. The type A cells in the synovium possessed numerous vesicles, vacuoles
      and lysosomes as well as pinocytotic vesicles. These ultrastructural features
      indicating phagocytosis showed distinct positive reactions following hyaluronan
      staining. On the other hand, in the type B cells, hyaluronic acids were present
      in the surface coat of the plasma membrane and its periphery. Additionally,
      perivascular connective tissue of the small capillaries and blood vessels and
      interfibrous matrix contained hyaluronan. The results suggest that hyaluronic
      acid, in the synovial tissue, is synthesized on the plasma membrane of type B
      cells, and taken up by type A cells. Moreover, hyaluronan is involved in cellular
      functions in the synovial connective tissue.

PMID- 15481847
TI  - Pediatric IgA nephropathy: clinical features at presentation and outcome for
      African-Americans and Caucasians.
AB  - AIM: To determine the disease severity at onset and outcome for African-American
      and Caucasian pediatric patients with IgA nephropathy diagnosed at the Le Bonheur
      Children's Medical Center since 1990. DESIGN/METHODS: The study population
      included all patients diagnosed with IgA nephropathy at the Le Bonheur Children's
      Medical Center from January 1990 through February 2004. All were below age 18 at
      biopsy. Clinical features assessed at diagnosis were age, gender, presence of
      hypertension, history of macroscopic hematuria, degree of proteinuria, severity
      of renal histology and pattern for immunofluorescent reactants. STATISTICS:
      Student's t-test was used to compare age at biopsy and length of follow-up
      between the 2 groups. Fisher's exact test was used to compare features at
      presentation and patterns of immunofluorescence. Kidney survival was predicted by
      the Kaplan-Meier method. RESULTS: Forty-seven patients (17 African-American, 29
      Caucasian) were studied. Clinical features at diagnosis and pattern for all
      immunofluorescent reactants did not differ significantly between the 2 groups.
      Mesangial deposition of C1q occurred in 4/17 African-Americans as compared to
      1/27 Caucasians (p = 0.06). Four patients (2 African-Americans, 2 Caucasians)
      progressed to end-stage renal disease. Predicted kidney survival was 96% (94% in
      African-Americans and 97% in Caucasians) at 1 year and 91% (94% in African
      Americans and 89% in Caucasians) at 5 years from diagnosis. Mean time from
      diagnosis to end-stage renal disease or last follow-up was 3.3 years (3.8 for
      African-Americans, 3.0 for Caucasians). Macroscopic hematuria occurred prior to
      diagnosis for 90% of the Caucasian as compared to 61% of the African-American
      patients (p = 0.03). Urinalysis was normal at last follow-up visit for 24% of
      African-American patients and 32% of Caucasian patients. CONCLUSION: In a
      relatively small sample from a single center, except for the difference in
      macroscopic hematuria, clinical features at diagnosis and outcome of IgA
      nephropathy appear similar for African-American and Caucasian pediatric patients.

PMID- 15481848
TI  - Close relationship of plasminogen activator inhibitor-1 4G/5G polymorphism and
      progression of IgA nephropathy.
AB  - BACKGROUND: The plasminogen activator inhibitor-1 (PAI-1) 4G/4G genotype
      influences the development of diabetic nephropathy and lupus nephritis. However,
      the association of the PAI-1 4G/4G genotype and IgA nephropathy (IgAN) has not
      been investigated. SUBJECTS AND METHODS: The PAI-1 and ACE polymorphisms were
      examined in 270 healthy volunteers and 202 biopsy-proven IgAN patients, including
      117 untreated IgAN patients who had an annual health check, allowing an
      estimation of the time of onset of overt proteinuria and/or hematuria. The
      relationship between the gene polymorphisms and the pathogenesis of IgAN were
      examined in 202 IgAN patients and the relationship between the gene polymorphisms
      clinical and pathohistological findings were examined in 117 untreated IgAN
      patients cross-sectionally at the time of renal biopsy. RESULTS: 202 IgAN
      patients and 117 untreated IgAN patients did not have different frequencies in
      PAI-1 4G/5G (4G/4G : 4G/5 : 5G/5G = 82 : 90: 30, 45 : 55 : 17) and ACE I/D (DD :
      ID : II = 41 : 82 : 79, 21 : 54 : 42) gene polymorphisms compared with 270
      healthy volunteers (4G/4G : 4G/5 : 5G/5G = 99 : 124 : 47, DD : ID : II = 53 : 106
      : 111). However, IgAN with 4G/4G had significantly more advanced histological
      changes than IgAN with 4G/5G or 5G/5G both in glomerular and tubulointerstitial
      findings (p < 0.0005). The disease duration in IgAN with 4G/4G was shorter than
      in IgAN with 4G/5G + 5G/5G (6.22 +/- 6.38 and 8.80 +/- 9.79 years, respectively,
      p < 0.05). Creatinine clearance (Ccr) in IgAN with 4G/4G was significantly lower
      than IgAN with 4G/5G or 5G/5G (72.3 +/- 26.5 and 82.4 +/- 22.8 ml/min,
      respectively, p < 0.05). The mean urinary protein excretion in IgAN with 4G/4G
      was significantly more than in IgAN with 4G/5G or 5G/5G (1.10 +/- 1.48 and 0.70
      +/- 1.01 g/day, respectively, p < 0.05). There was no difference between IgAN
      with the DD ACE genotype and IgAN with ID + II genotypes in either the clinical
      or histopathological findings. CONCLUSION: PAI-1 polymorphism is not associated
      with genesis of IgA nephropathy, but may be a risk factor for the progression of
      IgA nephropathy in Japanese.

PMID- 15481849
TI  - A novel splice site mutation of the thiazide-sensitive NaCl cotransporter gene in
      a Japanese patient with Gitelman syndrome.
AB  - Gitelman syndrome (GS, MIM 263800) is an inherited disorder characterized by
      metabolic alkalosis with hypokalemia, hypomagnesemia, and hypocalciuria. The
      genetic abnormalities causing GS are known to lie in the thiazide-sensitive NaCl
      cotransporter (TSC), which is expressed in the distal tubule of the kidney. The
      TSC gene, located at chromosome 16, consists of 26 exons and encodes the protein
      containing 12 putative transmembrane domains with long intracellular amino and
      carboxy termini. Most of the abnormalities identified in GS were missense
      mutations, distributed throughout the TSC gene without a hot spot. A 42-year-old
      Japanese man was introduced for close examination of hypokalemia. In renal
      clearance studies using furosemide or thiazide, chloride clearance was increased
      after furosemide but not after thiazide administration. Furthermore, the distal
      fractional chloride reabsorption was dramatically decreased by furosemide but not
      thiazide administration, suggesting a defect in the distal tubule. We then
      analyzed the TSC gene to confirm the diagnosis of GS, and identified a novel G to
      T mutation at the acceptor splice site preceding exon 14, resulting in disruption
      of a conventional 3'AG consensus splice site. Abnormal splicing by this mutation
      is predicted to cause the formation of truncated TSC with a partial deletion of
      the transmembrane domain, which will loose the function of transporter. In
      conclusion, we have identified a unique novel splice site mutation of the TSC
      gene in GS. The predicted structure of this mutant TSC can conceivably cause an
      impairment of the transporter activity and thereby be responsible for the
      development of GS in our patient.

PMID- 15481850
TI  - Sepsis and SOFA score: related outcome for critically ill renal patients.
AB  - AIMS: To evaluate the influence of sepsis in critically ill patients with acute
      renal failure (ARF), and to analyze the value of the sequential organ failure
      assessment (SOFA) score for assessing the morbidity and related mortality of
      these patients. MATERIAL AND METHODS: A prospective observational study developed
      in a medical intensive care unit (ICU) of a tertiary care university hospital.
      Data were collected from January 1, 2001 - July 31, 2002. The inclusion criterion
      was either a creatinine plasma level > or = 2 mg/dl on ICU admission or increases
      > or = 30% from its initial value. Sepsis was evaluated at the time of study
      inclusion, and patients were distributed into 2 groups (septic and nonseptic
      patients). RESULTS: Two hundred patients with ARF were prospectively enrolled in
      the study (91 (45.5%) septic and 109 (54.5%) nonseptic patients). Median age was
      68 years in septic patients and 72 in nonseptic ones while the percentage of
      males in both groups was 66% vs 69%, respectively. Septic patients showed more
      organ failures and more respiratory, cardiovascular and coagulation failures at
      the time of study admission as well as a worse mean SOFA score during the first 4
      days after inclusion (p < 0.01). Mortality rate at the ICU was significantly
      higher in the septic group when compared to the nonseptic one (55% vs 19.3%, OR =
      2.21 (1.65 - 2.97)). Using stepwise logistic regression, acute tubular necrosis
      and oliguria in septic patients as well as cardiovascular failure (evaluated by
      SOFA score) in nonseptic patients were identified as independent risk factors for
      mortality. CONCLUSIONS: Septic and nonseptic ICU patients with ARF have an
      increased risk of ICU mortality depending on the type of organ failure. Although
      SOFA score does not predict outcome, it is a useful tool to categorize these
      patients and to describe a sequence of complications in critically ill patients.

PMID- 15481851
TI  - Efficacy and safety of lanthanum carbonate for reduction of serum phosphorus in
      patients with chronic renal failure receiving hemodialysis.
AB  - BACKGROUND: Lanthanum carbonate is a highly effective phosphate binder with
      significant potential as a treatment for hyperphosphatemia in patients with end
      stage renal disease (ESRD). Here, the results of a placebo-controlled, dose
      ranging study are presented. METHODS: 196 patients (> or = 18 years) receiving
      hemodialysis for at least 6 months entered a 1- to 3-week, single-blind, placebo
      run-in phase. Of these, 145 patients were randomized to a double-blind phase in
      which they received placebo or lanthanum carbonate in daily lanthanum doses of
      225, 675, 1,350 or 2,250 mg for 6 weeks. Serum levels of phosphorus, calcium and
      parathyroid hormone, and adverse events were monitored throughout the study.
      RESULTS: The intent-to-treat analysis (n = 144) showed significant dose-related
      reductions in serum phosphorus at lanthanum doses of 675, 1,350 and 2,250 mg.
      After 6 weeks of treatment, phosphorus levels were significantly lower in the
      lanthanum groups receiving 1,350 mg/day and 2,250 mg/day, compared with the
      placebo group (respective changes from randomization: -0.95 +/- 1.39 mg/dl (-0.31
      +/- 0.45 mmol/l), -1.13 +/- 2.01 mg/dl (-0.36 +/- 0.65 mmol/l), 0.75 +/- 1.47
      mg/dl (0.24 +/- 0.47 mmol/l), p < 0.001). Significant reductions in serum
      phosphorus, compared with placebo, occurred in the lanthanum 1,350 mg/day group
      from the second week of treatment and in the 2,250 mg/day group from the first
      week of treatment. Adverse events were mainly gastrointestinal (e.g. nausea and
      vomiting). Treatment-related adverse events occurred in 39% of patients treated
      with lanthanum carbonate and 44% of the placebo group. CONCLUSION: Lanthanum
      carbonate is an effective and well-tolerated agent for the short-term treatment
      of hyperphosphatemia in patients with ESRD.

PMID- 15481852
TI  - High ratio of 1,25-dihydroxyvitamin D3 to parathyroid hormone in serum of
      tuberculous patients with end-stage renal disease.
AB  - AIM: Diagnosis of tuberculosis is sometimes difficult because of the low
      specificity of diagnostic procedures especially in patients on end-stage renal
      disease (ESRD). As abnormal vitamin D metabolism has been reported in
      tuberculosis, the aim of the present study was to determine whether serum
      concentration of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) may be a useful
      diagnostic indicator of tuberculosis in patients with ESRD. PATIENTS AND METHODS:
      Serum concentrations of 1,25-(OH)2D3, parathyroid hormone (PTH), and calcium were
      compared in 6 patients with ESRD and active tuberculosis (ESRD-TB group) and 110
      patients with ESRD and no tuberculosis (ESRD group). These parameters were
      compared before and after treatment for tuberculosis in patients of ESRD-TB
      group. RESULTS: Hypercalcemia was observed in all 6 patients in the ESRD-TB
      group. Both higher serum concentration of 1,25-(OH)2D3 and lower serum
      concentration of PTH were observed in the ESRD-TB group relative to the ESRD
      group, suggesting enhanced extrarenal production of 1,25-(OH)2D3 and suppressed
      secretion of PTH by hypercalcemia in the ESRD-TB group. However, these parameters
      could not be used to distinguish the ESRD-TB group from the ESRD group. The ratio
      of 1,25-(OH)2D3 to PTH in serum was above 0.9 in the ESRD-TB group and below 0.9
      in the ESRD group. Antituberculous treatment reduced this ratio to the range
      observed in the ESRD group. CONCLUSION: High ratio of 1,25-(OH)2D3 to PTH in
      serum is noted in active tuberculous patients with ESRD because of enhanced
      extrarenal production of 1,25-(OH)2D3.

PMID- 15481853
TI  - Evidence-based medical quality management in dialysis--Part I: Routine
      implementation of QiN, a German quality management system.
AB  - Increasing medical complexity, centrifugal forces of medical subspecialization
      and growing economic constraints are the key reasons for the introduction of
      quality management into routine care processes such as dialysis. Adequate quality
      assurance and improvement must be implemented in order to supply medical staff,
      care providers, and patients with the necessary information on critical issues of
      clinical management of dialysis patients. QiN (Quality in Nephrology), the
      quality management program of the largest German dialysis provider, is outlined
      here as a practicable example. The first of 2 parts provides information on the
      structure, implementation of QiN and achieved clinical improvement in routine
      care. The second part (quotation) analyzes longitudinal data in order to
      differentiate whether observed improvements during more than 5 years of QiN can
      be ascribed to the intervention (application of QiN) or whether they are due to
      other factors such as generally improved medical knowledge.

PMID- 15481854
TI  - Evidence-based medical quality management in dialysis--Part II: Improvement of
      hemodialysis adequacy.

PMID- 15481855
TI  - A possible favorable effect of colchicine in IgA nephropathy in a carrier of a
      MEFV mutation.
AB  - IgA nephropathy is the most common primary glomerulopathy. Currently, no
      satisfactory treatment is available and as a result, a significant proportion of
      affected patients progress to end-stage renal disease. We present a patient with
      IgA nephropathy in whom continuous colchicine treatment induced remission, which
      has lasted for 22 years. The patient was a carrier of a mutation in the FMF gene
      (MEFV). This case raises hopes for a better prognosis in at least one subgroup of
      IgA nephropathy, consisting of patients who happen to be heterozygous carriers of
      MEFV mutations.

PMID- 15481856
TI  - Widespread crystalline inclusions affecting podocytes, tubular cells and
      interstitial histiocytes in the myeloma kidney.
AB  - Numerous crystalline inclusions were observed in glomerular and tubular
      epithelial cells in a 46-year-old female patient with multiple myeloma and renal
      dysfunction. On light microscopy, epithelial cells were filled with homogenous
      materials and were remarkably swollen. Infiltrations of histiocytes with expanded
      cytoplasm were also seen in the interstitium of the kidney and bone marrow. On
      electron microscopy, cytoplasmic inclusions had crystalline structure showing
      rhomboid and oval shapes. Immunofluorescence study revealed that these cells were
      positive for IgG-kappa. The combination chemotherapy followed by autologous stem
      cell transplantation led to a partial resolution of her renal dysfunction,
      continued by a slight reduction in the number of crystalline-containing podocytes
      at the second renal biopsy. Crystal inclusions in the kidney are rarely found and
      cause renal impairment in multiple myeloma.

PMID- 15481857
TI  - Antineutrophil cytoplasmic antibody-associated necrotizing crescentic
      glomerulonephritis in a patient receiving treatment with etanercept for severe
      rheumatoid arthritis.
AB  - Etanercept is a tumor necrosis factor inhibitor used in the treatment of
      rheumatoid arthritis and, increasingly, in a range of other diseases. We report a
      case of necrotizing crescentic glomerulonephritis, associated with a positive
      antineutrophil cytoplasmic antibody, causing acute renal failure in a woman
      receiving treatment with etanercept for severe rheumatoid arthritis. Our patient
      was treated with steroids and cyclophosphamide following withdrawal of
      etanercept, with a good clinical response. Although reports of vasculitis in
      patients receiving treatment with etanercept are rare, this drug has been shown
      to up-regulate some aspects of immune function, and the possibility that this
      agent may precipitate or exacerbate vasculitis in some individuals has to be
      considered.

PMID- 15481858
TI  - Temporary suprarenal inferior vena cava filter for renal biopsy in a patient with
      renal vein thrombosis.

PMID- 15481859
TI  - The shorter T1/2 of cystatin C explains the earlier change of its serum level
      compared to serum creatinine.

PMID- 15481860
TI  - Sodium reduces calcium binding to albumin and fibrinogen.

PMID- 15481861
TI  - Effects of oxygen tension in the gas atmosphere during in vitro maturation, in
      vitro fertilization and in vitro culture on the efficiency of in vitro production
      of mouse embryos.
AB  - Effects of oxygen (O2) tension in the gas atmosphere during in vitro maturation
      (IVM), in vitro fertilization (IVF) and in vitro culture (IVC) on the efficiency
      of in vitro production of mouse embryos were examined. Mouse oocytes recovered
      from large antral follicles were subjected to IVM in Waymouth medium for 15, 16
      and 17 hr under 5 or 20% O2 and then subjected to IVF and IVC under 5 or 20% O2
      tension. Lowering the O2 tension in the gas atmosphere for IVM from 20 to 5%
      improved the cleavage rate after IVF when the oocytes were subjected to IVM for
      15 hr; however, no improvement in the cleavage rate was observed when the culture
      period for IVM was extended to 16 and 17 hr. Lowering the O2 tension to 5% for
      IVM and IVC improved the development of the cleaved oocytes to the blastocyst
      stage, regardless of the culture period for IVM. However, the O2 tension for IVF
      had no remarkable effect on the subsequent embryonic development. These results
      demonstrate that 5% O2 is superior to 20% O2 for IVM and IVC, and suggest that
      20% O2 for IVM may delay oocyte maturation and/or the acquisition of
      fertilizability and impair the developmental competence of oocytes.

PMID- 15481862
TI  - Iodine intake as a possible cause of discontinuous decline in sperm counts: a re
      evaluation of historical and geographic variation in semen quality.
AB  - In order to examine whether iodine supplements may have caused a global decline
      in sperm concentrations during the past several decades, the synchronicity of the
      decline in mean sperm counts and the introduction of iodine supplements was
      analyzed statistically. A positive correlation between the incidence of thyroid
      disease and sperm counts has been detected in Europe. In addition, it has been
      shown that sperm counts began falling around 1965 in the United States, 40 years
      after iodine supplements were introduced. Mean sperm counts before and after 1965
      were 111 x 10(6)/ml and 70 x 10(6)/ml, respectively, in calculations weighted by
      the number of subjects included in each individual publication. The timing of the
      declines coincided with the introduction of iodine supplements in the United
      States, France, and the United Kingdom. The implications are that the global
      decline in sperm concentrations may be caused by iodine intake. Geographical
      variation in the types of sperm count decline also appears to be present.

PMID- 15481864
TI  - Access to medical care top priority for new CEO.

PMID- 15481863
TI  - Adrenocortical responses to tumor necrosis factor-alpha and interferon-gamma in
      cattle.
AB  - The responses of plasma cortisol and adrenocorticotropic hormone (ACTH) were
      examined to intravenous injection of recombinant bovine tumor necrosis factor
      alpha (TNF-alpha) and interferon-gamma (INF-gamma) in Holstein cows. INF-gamma
      induced dose-dependent rises in the plasma levels of both cortisol and ACTH,
      while TNF-alpha induced comparable plasma cortisol responses with much smaller
      rises in plasma ACTH. The results suggest a direct stimulatory action of TNF
      alpha on cortisol secretion from the adrenal gland in cattle.

PMID- 15481865
TI  - Partnering with citizens to reform Wisconsin health care: a report of the first
      citizen congress.

PMID- 15481866
TI  - Heroin dependence.
AB  - Heroin use, particularly injection use, is a problem of great public health
      importance. The risks associated with heroin dependence, such as HIV and viral
      hepatitis, and the social costs due to associated crime and poverty exceed those
      of most other drugs of abuse. Increasing purity and decreasing cost of heroin
      likely contribute to trends of decreasing age at first use and an increasing rate
      of initiation into regular use in the United States. Effective treatment is
      available for heroin dependence, so primary care providers should screen patients
      for this disorder. This article reviews the epidemiology of heroin use and
      dependence in the United States and outlines what is known regarding risk factors
      for initiation of heroin use and for heroin dependence.

PMID- 15481867
TI  - Clean indoor air policies in Wisconsin workplaces.
AB  - OBJECTIVE: To describe the nature and extent of workplace environmental tobacco
      smoke exposures in Wisconsin. METHODS: Descriptive data and confidence intervals
      from the Current Population Survey tobacco supplements of 1995-1996 and 1998-1999
      are presented. RESULTS: The percent of indoor workers working under a smoke-free
      policy increased slightly, from 62% in 1995-1996 to 65% in 1998-1999. Respondents
      with a college degree were more likely to work under a smoke-free policy than
      those with a high school education or less. Among respondents with a work policy
      in 1998-1999, a complete ban on smoking reduced any workplace exposure in the
      past 2 weeks (4%) compared to a partial ban (26%) or an unrestricted policy
      (30%). CONCLUSION: Wisconsin has seen a small increase in workplace policies that
      ban smoking in the workplace. These policies are more likely to protect workers
      of higher socioeconomic status and may increase health disparities in tobacco
      related diseases in the future.

PMID- 15481868
TI  - Current management of patients with patent foramen ovale and cryptogenic stroke:
      our experience and review of the literature.
AB  - BACKGROUND: Patent Foramen Ovale (PFO) occurs in approximately 25% of the
      population and has been implicated in the etiology of cryptogenic stroke.
      Although the exact mechanism of PFO's role in stroke has not been defined, there
      is a growing body of evidence that supports both the safety and therapeutic
      benefit of PFO closure in cryptogenic stroke. Current methods of therapy include
      anticoagulation, surgical closure, and percutaneous closure. METHODS: We
      completed a retrospective analysis of data from the first 20 PFO closures at our
      institution and evaluated the current literature on PFO treatment. RESULTS:
      Percutaneous closure had a 100% technical success rate. There were no procedural
      complications and only 1 episode of supraventricular arrhythmia requiring
      therapy. CONCLUSION: Percutaneous closure is associated with a high technical
      success rate, decreased morbidity compared to surgery, and equal benefits after
      endothelialization of the device. As the mechanisms involved in PFO are better
      delineated, clear guidelines can be established for the percutaneous closure and
      follow-up of PFO.

PMID- 15481869
TI  - The growing medical and scientific challenges of obesity.

PMID- 15481870
TI  - Managing diabetic dyslipidemia: testing is step one.

PMID- 15481871
TI  - Are you emotionally ready to retire?

PMID- 15481872
TI  - 10 questions for Dr Phil.

PMID- 15481873
TI  - I've got a problem.

PMID- 15481874
TI  - A new report on radiation exposure casts a pall on a popular health test.

PMID- 15481875
TI  - Why is such a good word so misunderstood?

PMID- 15481876
TI  - Union nurses will be protected from new overtime regulations.

PMID- 15481877
TI  - An ounce of prevention.

PMID- 15481878
TI  - Michigan steps up!

PMID- 15481879
TI  - Can registered nurses really influence the election?

PMID- 15481880
TI  - A system with many methods to adjust staffing.

PMID- 15481881
TI  - PECSH negotiating team hones its skills.

PMID- 15481882
TI  - MNA joins Detroit Shock to reach young women.

PMID- 15481883
TI  - Hb Suan-Dok [alpha109(G16)Leu-->Arg; CTG-->CGG (alpha2)] described in a patient
      of African ancestry.
AB  - A 58-year-old Black female from Curacao (West Indies) was recently referred to
      our Laboratory for a persistent microcytic hypochromic anemia. An analysis 13
      years earlier had shown no abnormal hemoglobin (Hb) fractions and a balanced
      beta/alpha synthetic ratio. The hematological indices were again compatible with
      thalassemia and no abnormal fractions were observed on electrophoresis or high
      performance liquid chromatography (HPLC). None of the seven common alpha
      thalassemia (thal) deletion defects were present. Direct sequencing of the alpha2
      gene revealed a CTG-->CGG single base substitution at codon 109. This mutation
      was previously described in a Thai patient (Hb Suan-Dok), inducing Hb H disease
      in association with a - -(SEA) allele. In contrast with earlier reports we were
      unable to identify any native Hb fraction. The balanced beta/alpha ratio
      indicated that alpha2-Suan-Dok is formed but does not form tetramer formation
      unless alpha-thal is present.

PMID- 15481884
TI  - Molecular basis of beta-thalassemia in the population of Tunisia.
AB  - The present study attempts to delineate the spectrum of beta-thalassemia (thal)
      mutations in Tunisia by studying a large population from different parts of the
      country. A total of 285 unrelated subjects, 190 of whom had beta-thal major, 72
      with Hb S/beta-thal, one with Hb C/beta-thal, one with Hb O-Arab/beta-thal and 21
      beta-thal carriers, were studied. The molecular defects were detected in 97.7% of
      the beta-thalassemic chromosomes (n=475). Nineteen different beta-thalassemic
      alleles were identified. Two mutations, namely codon 39 (C-->T) and IVS-I-110 (G-
      >A) accounted for 70.0% of the studied chromosomes, followed by IVS-I-1 (G-->A)
      (4.5%). Five other mutations, frameshift codon (FSC) 44 (-C), codon 30 (G-->C),
      IVS-I-2 (T-->G), IVS-II-745 (C-->G), and FSC 6 (-A), are not uncommon in this
      population, while the remaining 11 mutations, IVS-I-5 (G-->A), -30 (T-->A),
      codons 25/26 (+T), IVS-I-6 (T-->C), FSC 5 (-CT), IVS-II-848 (C-->A), FSC 8 (-AA),
      -87 (C-->G), IVS-I-5 (G-->C), IVS-II-1 (G-->A) and IVS-II-849 (A-->C) are quite
      rare; four of these have not been previously reported in the Tunisian population.
      Potential origin and spread of these mutations to Tunisia are also discussed.

PMID- 15481885
TI  - Contribution to the description of the beta-thalassemia spectrum in Tunisia and
      the origin of mutation diversity.
AB  - We determined the spectrum of beta-thalassemia (thal) mutations in 118 affected
      unrelated patients with different forms of beta-thal. Using a combination of
      reverse dot-blot analysis, denaturing gradient gel electrophoresis (DGGE),
      polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) and
      direct nucleotide sequencing, we identified the largest spectrum of beta-thal
      mutations so far reported in Tunisia, and to the best of our knowledge, within
      the Mediterranean Basin. A total of 18 distinct alleles were detected at
      different frequencies, with two alleles [codon 39 (C-->T) and IVS-I-110 (G-->A)]
      predominating all others. Seven other alleles [frameshift at codon (FSC) 6 (-A),
      FSC 8 (-AA), codon 30 (G-->C), IVS-I-1 (G-->A), IVS-I-2 (T-->G), IVS-I-6 (T-->C),
      FSC 44 (-C)] were rare, and nine alleles [-29 (A-->G), IVS-I-2 (T-->C), IVS-I-5
      (G-->C), IVS-I-5 (G-->T), IVS-I-116 (T-->G), codon 37 (G-->A), IVS-II-1 (G-->A),
      IVS-II-745 (G-->C) and IVS-II-849 (A-->C)], albeit described elsewhere, are
      reported here in Tunisia for the first time. The codon 39 and IVS-I-110 mutations
      were the two predominant alleles occurring at frequencies of 43.8% and 10.8%,
      respectively. They are presumably the earliest mutations introduced into this
      country. The codon 39 allele could have been introduced in Tunisia during the
      Roman occupation. Similarly, the IVS-I-110 mutation might have been introduced by
      the Turkish and Phoenician influence. Both gene flow and private mutations may
      account for the diversity of alleles observed in Tunisia. These data provide the
      background for implementing prevention programs based on genetic counseling and
      prenatal diagnosis.

PMID- 15481886
TI  - The 'hot-spot' of Hb E [beta26(B8)Glu-->Lys] in Southeast Asia: beta-globin
      anomalies in the Lao Theung population of southern Laos.
AB  - Hb E [beta26(B8)Glu-->Lys], is the most common abnormal hemoglobin (Hb) in
      Southeast Asian populations. The hitherto highest frequencies of the Hb E gene
      (HBB*E) in large population samples, approximately 0.3, were observed in the
      southern part of northeastern Thailand. The finding of even higher frequencies in
      a small, isolated Austroasiatic group in Northeast Thailand prompted us to
      examine samples of three Austroasiatic populations in southern Laos (official
      designation: Lao Theung), an area inhabited by numerous ethnic groups belonging
      to the Mon-Khmer branch. Blood samples were collected from a total of 603 adult
      subjects. The HBB*E frequencies were 0.426 in the So of Khammuan Province, 0.433
      in the Alak/Ngeh of Sekong Province and 0.253 in the Oy of Attapeu Province. The
      HBB*E frequencies in the So and Alak/Ngeh are the highest observed in Southeast
      Asia in representative population samples. None of the common Southeast Asian
      beta-thalassemia (thal) mutations were found. The results are discussed with
      respect to natural selection by malaria, selection time, effects of beta-thal and
      the ethnic history of the population of Southeast Asia.

PMID- 15481887
TI  - Two new beta-chain variants: Hb Tripoli [beta26(B8)Glu-->Ala] and Hb Tizi-Ouzou
      [beta29(B11)Gly-->Ser].
AB  - Two new beta-globin chain variants: Hb Tripoli: codon 26, GAG-->GCG
      [beta26(B8)Glu-->Ala] and Hb Tizi-Ouzou: codon 29, GGC-->AGC [beta29(B11)Gly-
      >Ser] are described on the first exon of the beta-globin gene. The two variants
      are characterized by DNA sequencing and mass spectrometry (MS). Hematological
      abnormalities were found in the two carriers. The presence of microcytosis and
      hypochromia is explained by an additional homozygous 3.7 kb alpha(+) thalassemic
      deletion for the carrier of Hb Tizi-Ouzou. Hb Tizi-Ouzou showed a slight
      instability in vitro. The same hematological abnormalities associated with anemia
      are difficult to explain for Hb Tripoli's carrier in the absence of an alpha
      globin genes abnormality and could suggest a possible abnormal splicing.

PMID- 15481888
TI  - Molecular characterization of Hb Val de Marne [alpha133(H16)Ser-->Arg; AGC-->AGA;
      (alpha2)] in a Chinese family.
AB  - There have been two previous reports on Hb Val de Marne (Hb Footscray)
      [alpha133(H16)Ser-->Arg] in the literature, but the molecular characterization
      has hitherto not been described. Based on the Ser-->Arg transition, the presumed
      mutation was cited as AGC-->CGC of the alpha2- or alpha1-globin gene. We have
      found this variant in a 15-year-old Chinese girl and her father, and automated
      DNA sequencing revealed an AGC-->AGA mutation at codon 133 of the alpha2-globin
      gene. Since an increasing number of alpha-globin gene variants have been reported
      with the same protein alteration but with different mutations on the alpha1- or
      alpha2-globin genes, the mutation identified in the present family does not
      preclude the presence of other alpha-globin gene mutations leading to this
      hemoglobin (Hb) variant.

PMID- 15481889
TI  - Hb Belfast [beta15(A12)Trp-->Arg]: definition of the clinical and hematological
      phenotype.
AB  - We report the sixth occurrence of Hb Belfast [beta15(A12)Trp-->Arg], a mild,
      unstable beta chain variant, in a large family wherein nine subjects were
      affected. DNA analysis showed a TUG-->AGG mutation at codon 15 of the beta-globin
      gene, confirming a Trp-->Arg amino acid substitution. The oxygen affinity of the
      isolated variant was increased. The clinical phenotype is silent or very mild,
      the only clinical finding being an intermittent moderate jaundice.

PMID- 15481890
TI  - Hb Buffalo [alpha89(FG1)His-->Gln (alpha1)], observed solely and in the presence
      of an Hb S [beta6(A3)Glu-->Val] heterozygosity.
AB  - The hemoglobin (Hb) pattern of a 32-year-old Somali male living in The
      Netherlands, during routine diabetes mellitus monitoring, showed two more peaks
      in addition to the characteristic heterozygous Hb A/S pattern. A major peak of
      15% faster than Hb A, and a minor one of 10.8%, overlapping Hb A2 and the
      glycated Hb S1c fraction were present. The patient was not anemic or microcytic
      but had a low haptoglobin level, possibly indicating a slightly elevated red
      blood cell (RBC) turnover. Hb S was confirmed by a sickle test and at the DNA
      level. The DNA sequence of the alpha1 gene revealed a C-->G transversion at
      position 89, changing the local positively charged histidine to a neutral
      glutamine. This mutant has been previously described in a Yemenite woman and two
      apparently unrelated Somali males. Our case is the first showing Hb Buffalo in
      combination with Hb S and a G6PD deficiency, and is again observed in a Somali.
      No functional abnormalities associated with mutations at this amino acid residue
      are reported in the literature. Also, in this case no sign of any hematological
      abnormalities that could not be explained by the Hb S heterozygosity G6PD
      deficiency was found. The abnormal alpha chain is expressed at the expected rate
      and without thalassemic effect or instability. The mutated alpha chain seems to
      associate with a slight preference to the beta(A) (15%) rather than with the
      beta(S) counterpart. The sum of both Hb A(Buffalo) and Hb S(Buffalo) results in
      about 19-20% of total Hb. This figure is in agreement with a stable mutant of the
      alpha1 gene.

PMID- 15481891
TI  - Hb Yaounde [beta134(H12)Val-->Ala] in association with Hb C [beta6(A3)Glu-->Lys]
      in a Caucasian Portuguese family.
AB  - Hb Yaounde [beta134(H12)Val-->Ala] is a rare, silent and asymptomatic hemoglobin
      (Hb) variant. It was previously reported in a Black man from Cameroon, in
      association with Hb Kenitra [beta69(E13)Gly-->Arg], and was subsequently found
      and described as Hb Mataro in a sub-Saharan child. To date, Hb Yaounde has not
      been described in Caucasian people and molecular studies have never been
      performed. Here we describe a three-generation Caucasian Portuguese family in
      whom Hb Yaounde was found in association with Hb C [beta6(A3)Glu-->Lys] (in the
      proband) and in a heterozygous state (in the proband's mother). The Hb studies of
      the proband's hemolysate, performed by isoelectric focusing (IEF) and low
      pressure cation exchange chromatography, only revealed an Hb variant identified
      as Hb C by comparison with a control. However, analysis performed by reversed
      phase high-performance liquid chromatography (HPLC) showed two different beta
      chain variants and a complete absence of the normal beta chain. This uncommon Hb
      variant was identified as Hb Yaounde by DNA sequencing analysis of the beta
      globin gene (codon 134, GTG-->GCG). The beta-globin gene haplotypes were
      determined in all family members using polymerase chain reaction (PCR)-based
      methodology; Hb Yaounde was found to be associated with the Mediterranean
      haplotype II. This study is the first description of Hb Yaounde in Caucasian
      individuals, and its association with a Mediterranean haplotype supports the
      hypothesis of an independent genetic origin other than African.

PMID- 15481892
TI  - A C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism and G20210A
      mutation in the prothrombin gene of sickle cell anemia patients from Northeast
      Brazil.
AB  - The C677T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and the
      G20210A mutation at the 3' untranslated region (3'UTR) of the prothrombin gene
      may be considered to be genetic risk factors that contribute to the clinical
      heterogeneity in sickle cell disease. The current study investigated a group of
      sickle cell (SS) patients from Salvador-Bahia, Northeast Brazil in order to
      determine the prevalence of these polymorphisms, using the polymerase chain
      reaction (PCR) and restriction fragment length polymorphim (RFLP) techniques. Out
      of 69 SS patients diagnosed with the C677T MTHFR gene polymorphism, 13 (18.6%)
      were heterozygous and four (5.7%) homozygous. The G20210A mutation was not found
      in 50 SS patients investigated. These results became important once the C677T
      MTHFR gene polymorphism was found to be an independent risk factor for vascular
      disease, a common clinical event in sickle cell disease.

PMID- 15481893
TI  - Compound heterozygosity for two new mutations in the beta-globin gene [codon 9
      (+TA) and polyadenylation site (AATAAA-->AAAAAA)] leads to thalassemia intermedia
      in a Tunisian patient.
AB  - More than 200 mutations that are associated with beta-thalassemia (thal) have
      been found. In most cases, studies to detect a mutation in a patient is made
      easier because of the existence of geographical sets of mutations that allow the
      use of a dedicated mutation detection kit. We describe here a patient who
      originated from Tunisia, in whom we found two as yet unreported mutations,
      showing that even in a well-studied population a full gene study might be needed
      to characterize mutation(s).

PMID- 15481894
TI  - A novel alpha-thalassemia nonsense mutation in codon 23 of the alpha2-globin gene
      (GAG-->TAG) in a Tunisian family.
AB  - Herein we describe a novel alpha-thalassemia (thal) point mutation in the alpha2
      globin gene, found in a 3-year-old Tunisian girl who had Hb Bart's (gamma4) at
      birth, later on presenting with moderate anemia, microcytosis and hypochromia.
      She had a normal Hb A2 level and no abnormal hemoglobin (Hb) fraction. After
      excluding most of the common Mediterranean mutations, the alpha2-globin gene was
      sequenced and found to have a point mutation in the heterozygous state that
      creates a premature stop signal for translation (GAG-->TAG or Glu-->Term) at
      codon 23. The same mutation was also found in the mother in the heterozygous
      state, while the father had a normal sequence. The presence of the mutation was
      also confirmed by nucleotide sequencing of the opposite strand. Since the
      mutation creates a restriction site for the BfaI enzyme, a polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP)-based assay was
      established for screening purposes.

PMID- 15481895
TI  - An alpha-thalassemia phenotype in a Dutch Hindustani, caused by a new point
      mutation that creates an alternative splice donor site in the first exon of the
      alpha2-globin gene.
AB  - The proband is an elderly woman (79 years of age) of Surinamese-Hindustani
      origin, suspected of being a carrier of a nondeletional alpha-thalassemia (thal)
      because of a moderate microcytic hypochromic anemia at normal ferritin levels and
      in the absence of any other alpha-thal deletions. Sequence analysis revealed a
      silent mutation (GGC-->GGT) at codon 22 of the alpha2-globin gene. This mutation
      generates a splice donor site consensus sequence (GGTGAG) between codons 22 and
      23. The abnormally spliced mRNA leads to a premature termination between codons
      48 and 49. The presence of a downstream intron may induce the intracellular
      degradation of the affected mRNA, a pathway known as nonsense mediated decay
      (NMD), and this explains the alpha(+)-thal phenotype observed in the patient. The
      codon 22 (GGC-->GGT) transition described in this report is the first mutation
      creating a splice donor site in one of the alpha-globin genes.

PMID- 15481896
TI  - A frameshift at codons 77/78 (-C): a novel beta-thalassemia mutation.
AB  - We identified and characterized a novel beta-thalassemia (beta-thal) mutation due
      to a deletion of cytosine at codons 77/78 (-C) [CAC(His) CA- or CTG(Leu)--> -TG]
      found in a heterozygous state in four members of a Mexican family. The beta
      haplotype analysis performed on the family revealed that the frameshift at codons
      77/78 (-C) mutation in this family is associated with haplotype V [- + - - - + ]
      and framework 2. Ten beta-thal alleles with a cytosine deletion are described at
      the Globin Gene Server, two of which are very near codon 77. The molecular
      pathology of beta-thal in the Mexican population has been shown to be
      heterogeneous, because some Mediterranean, Asian, private and rare alleles have
      been observed, a similar fact as has been observed in populations with a low
      frequency of beta-thal.

PMID- 15481897
TI  - The beta-globin gene cluster haplotypes in sickle cell anemia patients from
      Northeast Brazil: a clinical and molecular view.
AB  - The beta(S)-globin haplotypes were studied in 78 sickle cell Brazilian patients
      from Bahia, Northeast Brazil, that has a large population of African origin.
      Hemoglobin (Hb) profiles were developed by high-performance liquid chromatography
      (HPLC), and beta(S)-globin gene haplotypes were determined by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. We
      identified 44 (55.0%) patients with the CAR/Ben (Central African Republic/Benin)
      genotype, 16 (20.0%) Ben/Ben, 13 (16.2%) CAR/CAR and seven (8.8%) with other
      genotypes. Analyses of the phenotypes showed clinical differences related only to
      Hb F levels and blood transfusion therapy; the presence of -alpha(-3.7)
      thalassemia (thal) demonstrated statistical significance when associated with
      hematocrit (p=0.044), MCV (p=0.0007), MCH (p=0.012) and spleen sequestration
      events. The haplotype diversity found in the present study can be justified by
      information about the origin of the slave traffic period in Bahia during the 19th
      century. The specific characteristics described among the Bahian sickle cell
      patients could be confirmed by increasing the number of patients with specific
      genotypes and further studies of genetic markers.

PMID- 15481898
TI  - Late emergence of polycythemia in a case of Hb Chandigarh [beta94(FG1)Asp-->Gly].

PMID- 15481899
TI  - DNA sequence of Hb Iowa.

PMID- 15481900
TI  - The obligation of the professional, the opportunity of the physician.

PMID- 15481901
TI  - The key to prevention and treatment of diabetes--education.

PMID- 15481902
TI  - Standards for the treatment of diabetes.

PMID- 15481903
TI  - Monitoring of the patient with diabetes.

PMID- 15481904
TI  - Complications of diabetes mellitus.

PMID- 15481905
TI  - Physician roles in improving cardiovascular health: counseling patients and
      involvement in the community.
AB  - Cardiovascular disease (CVD) is the leading cause of death in Kentucky. No
      previous research on Kentucky primary care physician concern for CVD--or possible
      roles in promoting cardiovascular health--has been published. We report here the
      results of an original research project addressing this information gap. The
      results provide an opportunity to review and discuss the evidence base relating
      to ways that primary care physicians can use their time, talents, and influence
      to have the greatest impact on the cardiovascular health of their patients and
      their communities, and we provide some specific guidance for how this can be
      done. We used a key informant survey of 241 primary care physicians in 26
      Kentucky counties to gather more information regarding physician concern for CVD
      and roles that physicians can play in promoting cardiovascular health. We found
      that the majority of respondents were concerned about cardiovascular disease and
      its risk factors, thought that public programs were important for the reduction
      of cardiovascular risk in their communities, and felt that tobacco settlement
      money was a valid resource for funding such programs. Three fourths of the
      physicians were willing to participate in community efforts to improve health.
      With varying frequency, the physicians reported that they used office visits to
      counsel patients and parents on reducing the risk factors for CVD. A majority of
      the physicians reported that they counseled smoking cessation in at least 75% of
      the office visits of smokers. However, only 9% of them counseled on the benefits
      of fruits and vegetables in at least 75% of office visits. We conclude that
      Kentucky primary care physician community leaders are concerned about the
      consequences of cardiovascular disease in their communities. In addition to
      counseling patients in their offices, they can have a role in community efforts
      to promote cardiovascular health.

PMID- 15481906
TI  - First do no harm.

PMID- 15481907
TI  - Advances in the management of localized breast cancer: an overview.

PMID- 15481908
TI  - On becoming an informed voter.

PMID- 15481909
TI  - A cancer clip.

PMID- 15481910
TI  - [Genetic determinants of Escherichia coli pathogenicity isolated from urine and
      feces of children with different clinical variants of urinary system infection].
AB  - In the process of examination of 156 children of different age groups 176 E. coli
      cultures were isolated; of these, 98 cultures were isolated from acute cystitis
      and pyelonephritis patients, 28--from urine in cases of aysmptomatic bacteriuria,
      30--from feces in cases of asymtomatc bacteriuria and intestinal dysbacteriosis,
      while 20 cultures--from feces of healthy children. In these bacteria the presence
      of genes associated with pathogenicity islets (PI) hlyA, hlyB, cnf-1, papC, sfaG
      and gene irp-2 (iron-regulated protein) was established with PCR. The detection
      rate of PI determinants in uropathogenic E. coli (UPEC) was shown to depend on
      the variants of the clinical manifestation of urinary tract infection. The total
      detection rate of PI gene fragments in UPEC cultures of different origin was
      indicative of their definitely less frequent occurrence in asymptomatic
      bacteriuria, observed simultaneously with intestinal dysbacteriosis, in
      comparison with acute urological infection. Practically the same detection rate
      of PI determinants in E. coli, isolated in asymptomatic bacteriuria in children,
      reflected high probability of genetic exchange in the above-mentioned fragments
      and made it possible to presume the existence of DNA sites, characteristic mainly
      of pathogenic clones. The established heterogeneity of the detection rate of PI
      determinants in E. coli clinical isolates requires further study.

PMID- 15481911
TI  - [Protease activity of Klebsiella pneumoniae of different virulence].
AB  - The study of substrate specificity and activity of proteolytic enzymes secreted
      by K. pneumoniae strains with different virulence was carried out. The strains
      were cultivated in a liquid semi-synthetic medium. The biomass was inactivated,
      and the supernatant fluid was separated from microbial cells by centrifuging. In
      the supernatant thus obtained and in the fractions isolated by gel filtration
      with the subsequent purification on DEAE Sepharose elastase-like, trypsin-like
      and chemotrypsin-like proteolytic activity was determined. In K. pneumoniae
      strains with different virulence only a single proteolytic enzyme--elastase with
      a mol. wt. of 21 kD--was detected. The protease activity of the supernatant
      culture fluid did not depend on the virulence of the strain and was equal to
      5,416-7,476 I.U./ml. The activity of the purified enzyme was 100% of the elastase
      like activity of the supernatant culture fluid. The most virulent K. pneumoniae
      strain K2, whose LD50 for white mice was less than 10 microbial cells, was
      characterized by lower elastase-like activity. The absence of correlation between
      protease activity and K. pneumoniae virulence may be explained by the fact that
      surface glycoproteins of eukaryotic cells are glycosilated and thus slightly
      accessible for proteases.

PMID- 15481912
TI  - [Level of colonization by Ureaplasma urealyticum of definite biovars in a group
      of women with different clinical symptoms].
AB  - To evaluate the level of U. urealyticum colonization of female urogenital tract,
      the method of the multiplex polymerase chain reaction (PCR) in the presence of
      two pairs of primers, corresponding to genes controlling U. urealyticum 16S rRNA
      and unique human osteopontin was used. The study of 93 clinical specimens showed
      no correlation between high colonization level and the presence of definite
      clinical manifestations of U. urealyticum infection. The determination of
      ureaplasmic biovars was carried out by the method of PCR in the presence of 3
      primers corresponding to the multiple-banded antigen (MBA) gene. Biovar parvo was
      detected in 85% of the specimens, biovar T960 in 11% and both biovars were
      detected in 4% of the specimens. The biovar distribution in the groups of women
      with different clinical symptoms was approximately similar. U. urealyticum of
      biovar T960 occurred more frequently (33% of the specimens) only in a group of
      women with vaginal discharge characteristic of inflammation.

PMID- 15481913
TI  - [Use of tomicid in prophylaxis of respiratory streptococcal infection in the
      organized groups of children of pre-school age].
AB  - The results of the approbation of the use of Tomicid for the prophylaxis of
      scarlet fever and other manifestations of streptococcal infection in an organized
      group of children of pre-school age are presented. The pronounced prophylactic
      effect of Tomicid, manifested by a reliable decrease of group A streptococcal
      carrier state, as well as in a decrease in morbidity in respiratory streptococcal
      infection among children in the test group in comparison with those in the
      control one. The simplicity of the use of the preparation (as throat gargle for 5
      days) makes it possible to regard this preparation as a promising remedy for the
      urgent prophylaxis of scarlet fever.

PMID- 15481914
TI  - [Seroepidemiological study of coronavirus infection in children and adults in St.
      Petersburg].
AB  - As the result of prolonged (17 years) observations of patients with acute
      respiratory infections hospitalized in basic departments of clinics of the
      Research Institute of Influenza, coronavirus infection was found to be the cause
      of respiratory diseases, on the average, in 12% of cases (in some years in 6.8%
      to 28.6% of cases). The analysis of extensive morbidity rates among different age
      groups of the population showed that children were affected by coronavirus
      infection 5-7 times more often than adults. Three year cycles of this infection
      were established. The periods of coronaviruses activation were accompanied by
      their detection in patient material by electron-microscopy, a sharp increase of
      immune response of patients as well as in the number of nosocomial infections and
      the proportion of the monoinfection of the coronavirus nature. Coronaviruses
      played the leading role among other viruses in the etiology of hospital
      respiratory infections. Mucosal antibodies to coronaviruses in the secretions of
      the nasal cavity proved to be more important than serum antibodies not only in
      protection from infection, but also in the pattern of clinical manifestations of
      the disease.

PMID- 15481915
TI  - [Strain-specific antibodies as an indicator of the circulation of wild
      poliomyelitis viruses and their role in the formation of collective immunity in
      the population].
AB  - Essential differences in the intensity of collective immunity to poliomyelitis in
      the donors of Moscow and Kaluga were established. To find out the nature of high
      characteristics of collective immunity to poliovirus, types 1 and 2, in the
      donors of Kaluga, strain-specific antibodies to wild and vaccine polioviruses
      were studied. In a considerable number of donors strain-specific antibodies to
      poliovirus, types 1 and 2, were detected. This made it possible to presume a
      sufficiently wide circulation of these viruses among the population of the city
      in the middle of the 20th century and, as a consequence, high level of collective
      immunity appeared. Strain-specific antibodies to poliovirus of type 3 were rarely
      detected. This made it possible to suggest that the circulation of viruses of
      this type among the population was limited. Immunity to viruses of this type was
      due only to immunization. For this reason the characteristics of collective
      immunity in the donors of Moscow and Kaluga coincided. The detection of strain
      specific antibodies to poliomyelitis virus allowed to retrospectively form the
      opinion of the spread and time of the circulation of wild poliomyelitis viruses
      in the population.

PMID- 15481916
TI  - [Variability of the clonal structure of Yersinia pseudotuberculosis population
      under different conditions].
AB  - In a series of experiments the dynamics of the clonal structure of Y.
      pseudotuberculosis population was evaluated by cytopathogenicity in soil extract,
      as well as in associations with blue-green algae (cyanobacteria) and infusoria,
      under different temperature conditions. In all variants of experiments made at
      low environmental temperature (10 degrees C) a considerable part of Y.
      pseudotuberculosis clones (25-40%) was found to be cytopathogenic, while at 22
      degrees C such clones were absent or had low cytopathogenicity. At the same time
      experiments made under the same temperature conditions (10 degrees C) showed the
      variability of the clonal structure of the bacterial population in different
      associations and sterile soil extract, as well as at different periods of the
      experiments. At low temperatures Y. pseudotuberculosis virulent (cytopathogenic)
      clones, in contrast to avirulent ones, were characterized by the presence of
      virulence plasmid p45, as well as high urease and catalase activity. The results
      of the experiments are discussed from the viewpoint of the clonal concept of
      bacterial populations and their pathogenicity.

PMID- 15481917
TI  - [Antigenic activity of oral whole-culture meningococcal serogroup B vaccine].
AB  - The whole-culture vaccine preparation of Neisseria meningitidis, serogroup B,
      obtained by cultivation in a computer-controlled bioreactor, was studied. The
      preparation was shown to contain antigenically active polysaccharide, outer
      membrane proteins, as well as lipooligosaccharide, faintly pyrogenic and with low
      toxicity. After oral immunization of rabbits a multiple increase in the levels of
      IgG antibodies to these antigens in their blood serum was noted during the period
      of observation (303 days).

PMID- 15481918
TI  - [Cross-reactions between the antigens of healthy pulmonary tissue and Moraxella
      catarrhalis].
AB  - The study of cross-reactions between healthy pulmonary tissue antigens and
      Moraxella catarrhalis with the use of SDS-electrophoresis and immunoblotting
      revealed that in the component of healthy pulmonary tissue with a mol. wt. of 40
      kD epitopes existed to which antibodies were produced, capable of cross reaction
      with the components of M. catarrhalis with a mol. wt. of 35 kD and 70 kD. In
      addition, the presence of cross-reactions between cytokeratin-8, protein
      contained in healthy pulmonary tissue, and M. catarrhalis antigens was
      established.

PMID- 15481919
TI  - [Anti-inflammatory cytokines of cervical secretions and the blood serum in women
      with genital infections].
AB  - In cervical secretions of healthy non-pregnant women of the reproductive age high
      concentrations of ant-inflammatory cytokines, greatly exceeding those in blood
      serum, were detected. During pregnancy the level of TNF-alpha in cervical
      secretions dropped. The inflammation of the uterus neck was accompanied by a drop
      in the levels of IL-alpha and IL-1beta and a rise in the level of IL-8 in
      cervical secretions in pregnant and non-pregnant women. Similar changes in the
      cytokine profile occurred also in the blood serum, but they were less pronounced
      and could be observed only in non-pregnant women. The threat of the interruption
      of pregnancy, developing simultaneously with cervicitis, was accompanied not only
      by changes in the levels of cytokines in cervical secretions, but also by a
      perceptible increase in the content of IL-1alpha in the blood serum.

PMID- 15481920
TI  - [Risk factors of pseudomonas infection in hemoblastosis patients].
AB  - A total of 67 patients with diseases of the blood system and infectious
      complications, admitted to the Hematological Department of the Novosibirsk
      Regional Clinical Hospital, were examined. For this study only patients with
      etiologically established diagnosis were taken. The study revealed that
      Pseudomonas sp., whose strains were susceptible to Ceftazidime in 100% of cases
      and resistant to Cefepime and Imipenem in 15-17% of cases, was the etiological
      agent of 13.6% of all cases of infectious complications in hemoblastosis
      patients. Infectious lesions of pulmonary parenchyma, the presence of chronic
      diseases of the respiratory tract in the medical history, neutropenia, artificial
      ventilation of the lungs were found to be adverse prognostic factors with respect
      to a high risk of Pseudomonas infection in such patients. Therapy with
      glucocorticosteroids and cytostatics, preceding antibacterial prophylaxis were
      not linked with the isolation of Pseudomonas from the patients exhibiting the
      same levels of lethality and severity of infectious complications.

PMID- 15481921
TI  - [PCR system for the detection of the RNA of hepatitis A virus].
AB  - The detection of the causative agent of hepatitis A in the patient's body is the
      necessary element of the diagnostics of this disease. In this work the PCR system
      for the analysis of the RNA of hepatitis A virus in the patient's blood is
      presented and characterized. The method of the detection of the RNA of hepatitis
      A virus is based on the "nest" principle and consists of two consecutive
      reactions. In the first reaction the reverse transcription and amplification with
      the external pair of primers are carried out. The product thus obtained is used
      as material for the second reaction with the internal pair of primers. This
      method was used for the study of 44 blood samples from hepatitis A patients and
      23 blood samples from healthy donors. The detection rate of the RNA of hepatitis
      A virus in blood samples from the patients was 82%. Viral RNA could be detected
      in the serum in 72% of cases, both in the serum and in mononuclear blood cells in
      20% of cases, in mononuclear blood cells only in 8% of cases.

PMID- 15481922
TI  - [Specific features of normal vaginal microflora in girls of preschool age].
AB  - The study of the vaginal microbial cenosis in 20 healthy girls aged 3-7 years did
      not confirm the notion on the dominating role of cocci (including epidermal
      staphylococci). The associations of 2-5 different microorganisms represented by
      more than 20 species in an amount of 4-6 Ig PFC/g of discharge were established.
      In the overwhelming majority of the examinees (84.2%) the microbial associations
      of the vagina were found to contain bifidobacteria. Gram positive cocci
      (staphylococci and streptococci) took the 2nd and 3rd places in the isolation
      rates and were detected in vaginal associations in 78.9% of the girls.
      Staphylococci were represented by 5 coagulase-negative staphylococcal species
      with S. simulans and S. epidermidis prevailing. Hemolytic streptococci variants
      alpha and beta were isolated in the proportion of 2:1. The latter belonged to
      serogroups C and F. No S. aureus, Lactobacillus sp., streptococci of groups A and
      B, yeast-like fungi were detected. Genital mycoplasms (M. hominis) could rarely
      be found in the vaginal discharge of the girls aged 3-7 years (5.3%). No resident
      and transitory components could be isolated from the normal vaginal microflora
      and no quantitative domination of any bacterial species (genus) was shown. The
      concentrations of all organisms in this association were moderate or low.

PMID- 15481923
TI  - [Intestinal microflora in workers of harmful industry].
AB  - Prolonged work in industry under unhealthy working conditions leads to
      disturbances in the normal intestinal microflora in employees. The content of
      bifidobacteria decreases simultaneously with an increase in the amount of
      opportunistic microorganisms. The degree of disturbances in intestinal
      microbiocenosis correlates with the length of service.

PMID- 15481924
TI  - [Changes in fine morphological structures of Escherichia coli, Staphylococcus
      aureus and spores of Bacillus anthracis vaccine strain STI under the action of
      the disinfectant "Veltolen"].
AB  - Changes in fine morphological structures of E. coli, S. aureus and spores of B.
      anthracis vaccine strain STI under the action of the disinfectant "Veltolen"
      manufactured by the Closed Joint-Stock Company "Velt", were evaluated. When used
      at concentrations of 0.0025-0.025%, the preparation induced the loosening of the
      cell wall in all microorganisms under study, the intensive formation of bubbles
      on the cell wall surface with their subsequent separation from the cell wall and
      the formation of "rosettes". In case of more prolonged exposure (up to 60
      minutes) and higher concentrations of the preparation these phenomena became more
      intensive and finally led to the destruction of bacterial cells.

PMID- 15481925
TI  - [Cultivation of Mycobacterium tuberculosis in cell culture].
AB  - The method of the cultivation of M .tuberculosis in cell subcultures was tested.
      Five consecutive passages of 2 M. tuberculosis strains were carried out with
      similar inoculation and cultivation conditions. Mycobacterial cells preserved
      their morphological characteristics in the course of all passages. The method of
      M. tuberculosis cultivation in subcultured cells made it possible to study of the
      physiology of M. tuberculosis under conditions, most approximated to the natural
      tuberculosis infection in humans.

PMID- 15481926
TI  - [Spoligotyping of mycobacterium tuberculosis isolates obtained from patients in
      the Samara region].
AB  - The spoligotyping of 138 M. tuberculosis isolates obtained on the territory of
      the Samara region made it possible to classify them as belonging to 27 groups.
      The largest cluster including 94 strains (68.1%) belonged to Peking spoligotype.
      As shown with the use of the commercial system INNO-LiPA, 78 out of 134 strains
      (58.2%) had mutations in different sites of gene pro B. The analysis of the
      markers of resistance to rifampicin in Peking spoligotype revealed that 65
      (83.9%) out of 90 such cultures had mutations in gene pro B, i.e. potentially
      these strains had multiple antimicrobial resistance. This work demonstrated the
      prevalence of Peking spoligotype in a prison antituberculosis colony (81.6%).

PMID- 15481927
TI  - [Cytomegalovirus infection in melanoma patients].
AB  - The occurrence of active cytomegalovirus (CMV) infection in 30 patients with skin
      melanoma, aged 18-76 years, was studied with the enzyme immunoassay, the direct
      immunofluorescence test and the polymerase chain reaction. The patients were
      divided into two groups: group I consisted of 20 patients examined in a month
      after radical surgical treatment, group II consisted of 10 patients at the stage
      of the process generalization. For comparison, group III was formed consisting of
      89 patients with diagnosed secondary immunodeficiency and clinical manifestations
      of CMV infection. The control group included 80 donors. The study showed that in
      group II the occurrence of active CMV infection was 4 times higher than in group
      I and practically coincided with the results registered in group III. In the
      evaluation of the immune status of the members of group II the most profound
      changes were revealed in T-cell mediated immunity and in phagocytic immunity; the
      adequate production of tumor necrosis factor alpha and interleukin 1beta was
      absent, which created prerequisites for the activation of CMV and the aggravation
      of the prognosis.

PMID- 15481928
TI  - [Antibodies to Yersinia enterocolitica and Proteus mirabilis in blood sera of
      rheumatoid arthritis patients].
AB  - Data on specific antibodies to the bacterial antigens of Yersinia enterocolitica
      (serovars 03, 09) and Proteus mirabilis in rheumatoid arthritis (RA) patients are
      presented. According to the data of some researchers, these organisms play some
      role in the pathogenesis of RA. The highest level of IgG antibodies to Y.
      enterocolitica antigens of both serovars was noted. The activity of specific IgG
      antibodies to serovar 03 was higher than that to serovar 09. In the sera of RA
      patients with P. mirabilis antgens the activity of IgM antibodies was higher.

PMID- 15481929
TI  - [T-lymphocyte subpopulations and tumor necrosis factor-alpha in patients with
      acute Flexner's dysentery].
AB  - In 41 patients aged 24-63 years with acute Flexner's dysentery T-lymphocyte
      subpopulations CD-3, CD-4, CD-8, IRI and the content of tumor necrosis factor
      alpha (TNF-alpha) in the blood serum were detected. The suppression of T-cell
      mediated immunity on account of the presence of CD-4 with decreased
      immunoregulatory index and an increased content of TNF-alpha were established.
      Changes in T-cell mediated immunity and TNF-alpha depended on the period and the
      severity of the diseases.

PMID- 15481930
TI  - [Selective nutrient medium for the isolation of Bacillus cereus].
AB  - A selective dried medium for the isolation of B. cereus from clinical material
      and foodstuffs has been developed. The medium has high selective properties which
      ensure the isolation of B. cereus from microbial association in pure culture,
      thus making it possible to accelerate further identification of the
      microorganisms.

PMID- 15481931
TI  - [Properties of Corynebacterium diphtheriae cultivated in the medium prepared from
      inedible raw materials].
AB  - A nutrient medium for the cultivation of C. diphtheriae toxigenic strain was
      developed on the basis of raw materials unsuitable for use as foodstuffs and its
      main physico-chemical and cultivation properties were studied. The morphological,
      cultural, biochemical and toxigenic properties of C. diphtheriae cultivated in
      the experimental medium with horse serum were evaluated. As revealed in this
      study, C. diphtheriae retained their properties after prolonged cultivation and
      storage in the newly developed medium, both liquid and with agar added. The
      medium has a number of advantages: it is economical, raw materials for its
      production are readily available, the medium is free of ballast substances.

PMID- 15481932
TI  - [Blood antigens in the AB0 system and susceptibility of humans to diphtheria].
AB  - The analysis of a large number of diphtheria cases (1326) at the peak of
      diphtheria morbidity in Russia (1993-1994) revealed that the intensity of
      antidiphtheria antitoxic immunity was age-dependent with a sharp immunodeficiency
      in the population aged 35 years and older. As adaptive capacity of the organism
      decreases, the positive associative links between immunity to diphtheria and the
      AB0 blood groups become evident. Populations with phenotype B (III) had the
      largest diphtheria immune stratum at the age of 35 years and over as compared to
      3 other phenotypes. The genotypic analysis of serological data may be of
      practical importance for the detection of the degree of predisposition of humans
      to infectious diseases.

PMID- 15481933
TI  - [Disturbances in immunological reactivity in women with tuboperitoneal
      sterility].
AB  - The role of immune disturbances on the systemic and local levels is evaluated and
      the immunological mechanisms of tuboperitoneal sterility as the basis for the
      development of the methods of immunocorrection is grounded.

PMID- 15481934
TI  - [Immune status and proinflammatury cytokines in pregnant women with acute
      cytomegalovirus infection].
AB  - A total of 64 pregnant women aged 16-40 years with acute cytomegalovirus (CMV)
      infection were examined. CMV infection was diagnosed by the detection of anti-
      CMV IgM (by the enzyme immunoassay) or DNA by PCR in the blood. The
      immunophenotype of lymphocytes CD3+, CD4+, CD8+, CD16+, CD19+, IgG, IgM, IgA and
      the spontaneous production of TNFalpha and IL-8 in the blood were studied. In
      pregnant women with CMV infection the presence of the immunosuppression of cell
      mediated immunity reactions, the hyperproduction of Fc-receptors of natural
      killers, B lymphocytes (CD19+), the hyperglobulinemia of serum IgM and IgG, as
      well as the increased synthesis of proinflammatory cytokines--TNFalpha and IL-8-
      were established.

PMID- 15481935
TI  - [Crimean-Congo haemorrhagic fever in southern Russia].
AB  - At the end of the 20th--the beginning of the 21st century activation of a natural
      focus of Crimean-Congo haemorrhagic fever (CCHF) in southern Russia was noted. As
      a consequence, in 2002 outbreaks and sporadic cases of this disease were
      registered on the territory of 6 out of 13 administrative units of the Southern
      Federal District. To minimize the epidemiological consequences of the aggravating
      epidemiological situation considerable efforts and means were required from
      health care organs and institutions of the state sanitary and epidemiological
      service, including essential financial expenditures. The results of natural foci
      of CCHF survey, obtained by 2002, as well as main trends of prophylactic and
      antiepidemic interventions are presented. Scientific research and practical
      observations made it possible to work out a number of methodological regulations
      concerning the diagnostics, treatment and prophylaxis of CCHF.

PMID- 15481936
TI  - [Immunoregulation of the population of intestinal gram-negative microflora].
AB  - The authors present summarized data obtained in their studies on the presence of
      close feedback relationship between the state of immunity to common antigenic
      determinants of lipopolysaccharides (LPS), localized on the cell-wall surface of
      Gram-negative bacteria, and the development of intestinal dysbacteriosis. The
      problems dealing with the regulation of the amount of intestinal microflora with
      immunity factors taking part in the mechanism of such regulation are discussed
      and analyzed. The state of immunity to common antigenic determinants of LPS of
      Gram-negative bacteria re-flects, seemingly, the total resistance level of the
      body, i.e. the functional state of the immune system as a whole. The suggestion
      has been made that the development of intestinal dysbacteriosis may be basically
      caused by functional disturbances of the immune system, induced by different
      exogenous and endogenous damaging factors.

PMID- 15481937
TI  - [Genomics and gene engineering: rationale to the development of new means of
      tuberculosis control].
AB  - The review contains information on modern approaches to the development of
      antituberculosis vaccines and remedies. Data on the comparative effectiveness of
      different subunit and DNA vaccines against tuberculosis are presented. The use of
      comparative and structural genomics for the search and characterization of new
      Mycobacterium tuberculosis genes, whose products may prove to be important
      antigens for the development of vaccines or target proteins for remedies against
      tuberculosis, is considered.

PMID- 15481938
TI  - [Biocenosis of the natural foci of sapronotic infections (the results of 15-year
      observations)].
AB  - The summarized results of original studies, carried out in 1988-2003 by
      scientists of the Gamaleya Research Institute of Epidemiology and Microbiology,
      are discussed. The part dealing with the regularity and mechanisms of the
      circulation of pathogenic bacteria in the biocenosis of soil and water reservoirs
      includes the following subjects: population and intracellular interactions with
      protozoa; the evaluation of different representatives of hydrobios as hosts and
      the transmission along trophic biocenotic chains; the effect of algae and their
      metabolic products on bacterial populations; the possibility of the colonization
      of higher plants from the soil and the subsequent infection of rodents; the
      variability and clonal structure of bacterial population in its interaction with
      protozoa and plants; the chain of Yersinia circulation in agrocenosis. The part
      dealing with the mechanisms of the prolonged reservation of causative agents
      includes such subjects as the reversible transition of bacteria into the latent
      (uncultivable) state in soils and water reservoirs, as well as the biological
      inductors of this process; the prolonged preservation of latent bacteria in the
      cysts of protozoa and blue-green algae; the indication of causative agents in the
      natural foci of plague and pseudotuberculosis. On the basis of the original
      investigations and the data of literature new theoretical review in the field of
      the natural foci and the epidemiology of sapronotic infections have been
      formulated.

PMID- 15481939
TI  - [Specific prophylaxis of influenza with inactivated split vaccine Vaxigrip].
AB  - Influenza remains a serious health problem, annually causing epidemics embracing
      up to 10% of the population of the world, and at the periods of pandemics this
      number may rise 4- to 6-fold. In the overwhelming majority of the countries the
      prophylaxis of influenza is carried out at present out with the use of
      inactivated vaccines. One of such vaccines is the highly purified split vaccine
      Vaxigrip (Aventis-Pasteur, France), permitted for use in Russia since 1992. The
      article contains the review of the data of literature, as well as the materials
      provided by the authors, which indicate that the preparation has low
      reactogenicity (also for children starting from the age of 6 months) and high
      reactogenic properties, leading to antibody formation at protective levels with
      respect to all three components of the vaccine. The vaccine has been found to
      ensure pronounced prophylactic efficacy for 70-90% of vaccinees and a decrease in
      influenza morbidity even in case of using the preparation a week before the onset
      of the epidemic. This shows the advantage of Vaxigrip in comparison with other
      inactivated vaccines.

PMID- 15481940
TI  - [Epidemic outbreak of dermatophytia in a school of general education (part 1)].

PMID- 15481941
TI  - [Epidemic outbreak of trichophytia in a school of general education (part 2 with
      the author's commentary)].

PMID- 15481942
TI  - [Serological survey of the population in the territory endemic for Ixodes tick
      borne borreliosis].

PMID- 15481943
TI  - Separate visual representations in the planning and control of action.
AB  - Evidence for a dichotomy between the planning of an action and its on-line
      control in humans is reviewed. This evidence suggests that planning and control
      each serve a specialized purpose utilizing distinct visual representations.
      Evidence from behavioral studies suggests that planning is influenced by a large
      array of visual and cognitive information, whereas control is influenced solely
      by the spatial characteristics of the target, including such things as its size,
      shape, orientation, and so forth. Evidence from brain imaging and neuropsychology
      suggests that planning and control are subserved by separate visual centers in
      the posterior parietal lobes, each constituting part of a larger network for
      planning and control. Planning appears to rely on phylogenetically newer regions
      in the inferior parietal lobe, along with the frontal lobes and basal ganglia,
      whereas control appears to rely on older regions in the superior parietal lobe,
      along with the cerebellum.

PMID- 15481944
TI  - Constructing an understanding of mind: the development of children's social
      understanding within social interaction.
AB  - Theories of children's developing understanding of mind tend to emphasize either
      individualistic processes of theory formation, maturation, or introspection, or
      the process of enculturation. However, such theories must be able to account for
      the accumulating evidence of the role of social interaction in the development of
      social understanding. We propose an alternative account, according to which the
      development of children's social understanding occurs within triadic interaction
      involving the child's experience of the world as well as communicative
      interaction with others about their experience and beliefs (Chapman 1991; 1999).
      It is through such triadic interaction that children gradually construct
      knowledge of the world as well as knowledge of other people. We contend that the
      extent and nature of the social interaction children experience will influence
      the development of children's social understanding. Increased opportunity to
      engage in cooperative social interaction and exposure to talk about mental states
      should facilitate the development of social understanding. We review evidence
      suggesting that children's understanding of mind develops gradually in the
      context of social interaction. Therefore, we need a theory of development in this
      area that accords a fundamental role to social interaction, yet does not assume
      that children simply adopt socially available knowledge but rather that children
      construct an understanding of mind within social interaction.

PMID- 15481945
TI  - Charge-transfer matrixes as a tool to desorb intact labile molecules by matrix
      assisted laser desorption/ionization. Use of 2,7-dimethoxynaphthalene in the
      ionization of polymetallic porphyrins.
AB  - 2,7-Dimethoxynaphthalene (DMN) is proposed as matrix to investigate the structure
      of polymetallic porphyrins through matrix-assisted laser desorption/ionization
      tandem time-of-flight experiments. The peculiarity of DMN is represented by the
      formation of molecular radical cations and of some diagnostic fragments only. The
      traditional matrixes do not afford the expected molecular species. The
      experiments have been performed on extremely labile species such as zinc
      porphyirinate complexes with aluminum and gallium quinolinate to prove the
      softness of the methodology.

PMID- 15481946
TI  - Strategy for profiling and structure elucidation of mucin-type oligosaccharides
      by mass spectrometry.
AB  - A strategy combining accurate mass determination, tandem mass spectrometry,
      structure homology, and exoglycosidases is described that allows the structural
      characterization of mucin-type O-linked oligosaccharides. The method is used to
      profile with quantitation the O-linked oligosaccharide (both neutral and anionic)
      components of the only diploid Xenopus frog, Xenopus tropicalis. Collision
      induced dissociation was used to determine connectivity, to identify previously
      characterized oligosaccharides, and to determine the presence of structural
      motifs in unknown oligosaccharides. Exoglycosidase digestion was used to identify
      the individual residues along with the linkages. The enzymes were also used to
      cleave larger oligosaccharides to smaller units that are similar to previously
      elucidated components. By using CID, isomeric structures were compared to
      determine whether they were identical. In this way, the exoglycosidases were more
      effectively used, and their use was minimized. A total of 35 oligosaccharides
      including neutral, sialylated, and sulfated were characterized in this way. The
      relative abundances of all components were also determined based on HPLC.

PMID- 15481947
TI  - Identification of a photooxygenation product of chlortetracycline in hog lagoons
      using LC/ESI-ion trap-MS and LC/ESI-time-of-flight-MS.
AB  - In the present work, a photoproduct of chlortetracycline (CTC) was identified for
      the first time in hog lagoon samples from confined animal feeding operations.
      Screening of several samples by LC/ESI-MS indicated the presence of a potential
      photooxygenation product of CTC with a nominal mass that was 32 Da higher than
      the parent drug. Generation of this assumed photoproduct (designated M510) was
      achieved in a 24-h irradiation experiment of an oxygenated alkaline medium
      containing 50 mg L(-)(1) CTC. Accurate mass measurements with an ESI-TOF-MS of
      the protonated isomerization product of CTC (iCTC) and the postulated
      photooxygenation product, bearing two oxygen atoms more than iCTC, were m/z
      479.1229 and 511.1109, respectively. These corresponded to errors of -2.8 ppm for
      iCTC and +1.0 ppm for M510 relative to the theoretical masses. The generation of
      second- and third-stage mass spectra in an ESI-ion trap-MS showed similar
      characteristic fragmentation patterns for iCTC and the photoproduct M510, leading
      to the conclusion that the M510 structure consisted of an iCTC-like skeleton
      bearing two additional hydroxy groups. The site and configuration of one
      hydroxylation was confidently assigned, while the position of the other hydroxy
      group was tentatively assigned. Comparison of the (+)-ESI-MS(3) spectrum and the
      retention time of M510 in the sample from the irradiation experiment with those
      from the hog lagoon samples yielded excellent agreement, suggesting that the
      compounds were identical. Quantitative analysis of seven hog lagoon samples
      showed iCTC concentrations of 1910-15 800 microg L(-)(1), while the levels of
      M510 were found to be between 46 and 303 microg L(-)(1).

PMID- 15481948
TI  - Detection and quantification of lanthanide complexes in cell lysates by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Gadolinium (III) complexes are under intense scrutiny as contrast agents for
      magnetic resonance imaging. Although currently used mainly as extracellular
      agents, there is a growing interest to exploit their contrast enhancing ability
      in the intracellular environment. To ascertain the preservation of their chemical
      integrity upon the intracellular entrapment, it is necessary to have a method for
      their dosage in the cell lysates. Herein, a mass spectrometric method for
      detection and quantification of gadolinium complexes in cell lysates is reported.
      The detection by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS) was carried out by using a non-acidic matrix (2,4,6
      trihydroxyacetophenone), which does not allow any leakage of gadolinium from the
      complex. Quantification has been possible by using as an internal standard an
      ytterbium complex with the same ligand of the analyte. Ytterbium was chosen
      because, among the lanthanides, it is the one with the isotopic distribution
      pattern the most similar to that of gadolinium. Sensitivity was enough to detect
      low micromolar quantities of a cationic complex and high micromolar quantities of
      a neutral complex in cell lysates of rat hepatoma cells. In the case of anionic
      complexes, sensitivity was too low for quantitative analysis. To the best of our
      knowledge, this is the first report concerning the quantification of metal
      complexes by MALDI-TOF-MS.

PMID- 15481949
TI  - Increased identification of peptides by enhanced data processing of high
      resolution MALDI TOF/TOF mass spectra prior to database searching.
AB  - This paper presents application of sequential enhanced data processing procedures
      to high-resolution tandem mass spectra for identification of peptides using the
      Mascot database search algorithm. A strategy for (1) selection of fragment ion
      peaks from MS/MS spectra, (2) utilization of improved mass accuracy of the
      precursor ions, and (3) wavelet denoising of the mass spectra prior to fragment
      ion selection have been developed. The number of peptide identifications obtained
      using the enhanced processing was then compared with that obtained using software
      provided by the instrument manufacturer. Approximately 9000 MS/MS spectra
      acquired by the Applied Biosystems 4700 TOF/TOF MS instrument were used as a
      model data set. After application of the new processing, an increase of 33%
      unique peptides and 22% protein identifications with at least two unique peptides
      were found. The influence of the processing on the percentage of false positives,
      estimated by searching against a randomized database, was estimated to increase
      false positive identifications from 2.7 to 3.9%, which was still below the 5%
      error rate specified in the Mascot search. These data processing approaches
      increase the amount of information that can be extracted from LC-MS analysis
      without the necessity of additional experiments.

PMID- 15481950
TI  - Membrane-assisted solvent extraction of triazines, organochlorine, and
      organophosphorus compounds in complex samples combined with large-volume
      injection-gas chromatography/mass spectrometric detection.
AB  - The performance of the fully automated membrane-assisted solvent extraction was
      investigated for 47 environmental contaminants (among them 30 organochlorine
      compounds, 9 organophosphorus compounds, and 7 triazines). The extraction took
      place in a 20-mL headspace vial filled with the aqueous sample and containing a
      polypropylene membrane bag with 1 mL of cyclohexane as extractant. This device
      was handled by a multipurpose sampler, which enabled the sample to be mixed at a
      defined temperature with subsequent large-volume injection of the organic extract
      taken out of the membrane bag. After optimization of extraction parameters, the
      method was validated for the three compound classes, triazines and organochlorine
      and organophosphorus compounds, using spiked distilled water. Then, the
      extraction yield of these analytes from several complex samples such as a natural
      and a synthetic wastewater, a bacterial culture, and orange juice was determined
      and compared to a conventional liquid-liquid extraction. Furthermore, the
      possibility of reducing matrix interference by adding salt, methanol, or
      detergent during membrane-assisted solvent extraction was investigated.

PMID- 15481951
TI  - MALDI-TOF mass spectrometric detection of multiplex single base extended primers.
      A study of 17 y-chromosome single-nucleotide polymorphisms.
AB  - One of the most promising techniques for typing of multiple single-nucleotide
      polymorphism (SNP) is detection of single base extension primers (SBE) by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS). We present a new MALDI-TOF MS protocol for typing of multiple SNPs in a
      single reaction. Biotin-labeled ddNTPs were used in the SBE reaction and solid
      phase-bound monomeric avidin was used as capturing/purification scheme allowing
      the exclusive release of the SBE products under gentle conditions using 5%
      triethylamine. We dubbed this method monomeric avidin triethylamine purification.
      The biotin-labeled ddNTPs contained linkers with different masses ensuring a
      clear separation of the alleles even for SBE primers with a mass of 10 300 Da.
      Furthermore, only 25-350 fmol of SBE primers were necessary in order to obtain
      reproducible MALDI-TOF spectra. Similar signal intensities were obtained in the
      5500-10 300 m/z mass range by increasing the concentration of the longer SBE
      primers in the reaction. To validate the technique, 17 Y-chromosome SNPs were
      analyzed in 200 males. The precision and accuracy of the mass determination were
      analyzed by parametric statistic, and the potential use of MALDI-TOF MS for SNP
      typing is discussed.

PMID- 15481953
TI  - Strategy for repetitive pinched injections on a microfluidic device.
AB  - A microfluidic valve was fabricated with a cross intersection and two tee
      intersections in close proximity and evaluated for repetitive pinched injections.
      Electrokinetic forces were used to mobilize the sample and control diffusive
      transport at a cross intersection to produce sample plugs of short axial extent
      in an analysis channel similar to the standard pinched valve. The addition of a
      tee intersection in the sample channel maintained the sample close to the
      injection valve under "pullback"conditions allowing more rapid loading into the
      cross intersection. A second tee intersection allowed unidirectional transport in
      the analysis channel enabling loading of subsequent injections during an
      analysis. The two tee intersections were each located 80 microm from the cross
      intersection. Injection frequencies of 1, 2.5, 5, and 10 Hz were tested with a
      duty cycle of 0.5 for sample loading and dispensing. With 1 kV applied to the
      microchip during dispensing, the relative standard deviation of the peak areas
      for 15 injections was 1.6%. The peak width (4sigma) for the repetitive injections
      increased from 71 to 96 microm compared to a standard pinched injection due to
      the presence of the tee intersection in the analysis channel.

PMID- 15481952
TI  - Direct electron transfer of cytochrome P450 2B4 at electrodes modified with
      nonionic detergent and colloidal clay nanoparticles.
AB  - A method for construction of biosensors with membranous cytochrome P450
      isoenzymes was developed based on clay/detergent/protein mixed films. Thin films
      of sodium montmorillonite colloid with incorporated cytochrome P450 2B4 (CYP2B4)
      with nonionic detergent were prepared on glassy carbon electrodes. The modified
      electrodes were electrochemically characterized, and bioelectrocatalytic
      reactions were followed. CYP2B4 can be reduced fast on clay-modified glassy
      carbon electrodes in the presence of the nonionic detergent Tween 80. In
      anaerobic solutions, reversible oxidation and reduction is obtained with a formal
      potential between -0.292 and -0.305 V vs Ag/AgCl 1 M KCl depending on the
      preparation of the biosensor. In air-saturated solution, bioelectrocatalytic
      reduction currents can be obtained with the CYP2B4-modified electrode on addition
      of typical substrates such as aminopyrine and benzphetamine. This reaction was
      suppressed when methyrapone, an inhibitor of P450 reactions, was present.
      Measurement of product formation also indicates the bioelectrocatalysis by
      CYP2B4.

PMID- 15481954
TI  - In vitro characterization of microdialysis sampling of macromolecules.
AB  - Experiments were performed to characterize the in vitro collection of
      macromolecules using microdialysis. Fluorescently labeled proteins and dextrans
      ranging from 3000 to 150 000 were sampled using a 10-mm, 100 000 molecular weight
      cutoff, polyethersulfone microdialysis probe. Published models describing
      microdialysis mass transport of small molecules were examined to determine their
      appropriateness for sampling of macromolecules. Collection efficiencies, reported
      as relative recoveries, for macromolecules from 3000 to 70 000 ranged from 5 to
      44%. Collection efficiencies determined for microdialysis sampling of
      macromolecules follow the functionality of published models, although
      experimental mass transport resistances are to some extent smaller than
      predicted. Implications of the current study for in vivo microdialysis sampling
      of cytokines and growth factors are discussed.

PMID- 15481955
TI  - Partial modulation method via pulsed flow modulator for comprehensive two
      dimensional gas chromatography.
AB  - A partial modulation method by using a pulsed-flow modulator for comprehensive
      two-dimensional gas chromatography is proposed. The method is based on the fact
      that when a pulsed flow of inert gas is introduced into the conjunction between a
      primary and a secondary column, the concentration of analyte is disturbed, and a
      plug of higher or lower concentration is created. The plug, which forms a spike
      signal coupled to the primary GC signal, is then separated in a secondary column,
      creating a new dimension of GC information. The modulation is partial because
      only a fraction of the primary signal is modulated and converted into the
      secondary signal; the remaining primary signal stays unchanged. Therefore, this
      method yields a comprehensive two-dimensional chromatogram and a primary one
      dimensional chromatogram in a single GC run. In this study, the modulation mode,
      modulation index, and modulation percentage are discussed and the reproducibility
      of peak areas and retention time are investigated. With a 5.8% modulation
      percentage and a primary peak half-width 1.7 times wider than the modulation
      time, the standard deviation for the peak areas are 0.15% for the primary and
      0.78% for the secondary chromatograms. Chromatograms of laboratory-mixed
      hydrocarbons and of high-temperature fuel oil no. 6 standard are demonstrated.

PMID- 15481956
TI  - Analysis of polyacrylamide gels for trace metals using diffusive gradients in
      thin films and laser ablation inductively coupled plasma mass spectrometry.
AB  - A simple method for the analysis of polyacrylamide diffusive gradients in thin
      film (DGT) gels by laser ablation inductively coupled plasma mass spectrometry
      (LA-ICPMS), employing a novel use of (115)In internal standardization, has been
      developed. This method allows the determination of Co, Ni, Cu, Zn, Cd, and Pb
      concentrations (at the DGT filter face) or fluxes in sediments at a spatial
      resolution of 100 microm. Single-layered gels, using an optimized laser defocus
      of 4000 microm at 400 mJ power, showed high precision (generally approximately
      10%) and a linear response during solution deployment. Of the elements Sc, In,
      Ba, La, Ce, and Tb, Ba most closely tracked variations in laser energy and showed
      the highest analytical precision but could not be used as an internal standard
      due to its elevated presence in natural sediments. Therefore, internal
      standardization, necessary to normalize data collected on different days, was
      carried out using (115)In contained within a second layer of backing gel and
      dried along with the analyte layer as a dual-gel disk. This multilayered gel
      standard required a laser defocus setting of 1000 microm and a laser power of
      approximately 800 mJ. Analytical precision for a 64-spot ablation grid at 100
      microm spacing was approximately 10%. Verification of this method was carried out
      on DGT sediment probes deployed in Priest Pot (English Lake District). Results
      obtained by conventional slicing techniques and aqueous elution agreed with laser
      ablation results when the different sampling areas were considered. The elution
      results varied by a factor of <2, whereas the laser ablation technique showed a
      variability of approximately 4, indicating localized elevated concentrations of
      Co. This higher resolution LA-ICPMS method could ultimately lead to an improved
      understanding of the geochemical processes responsible for metal uptake and
      release in sediments.

PMID- 15481957
TI  - Differential mass spectrometry: a label-free LC-MS method for finding significant
      differences in complex peptide and protein mixtures.
AB  - Efficiently identifying and quantifying disease- or treatment-related changes in
      the abundance of proteins is an important area of research for the pharmaceutical
      industry. Here we describe an automated, label-free method for finding
      differences in complex mixtures using complete LC-MS data sets, rather than
      subsets of extracted peaks or features. The method selectively finds
      statistically significant differences in the intensity of both high-abundance and
      low-abundance ions, accounting for the variability of measured intensities and
      the fact that true differences will persist in time. The method was used to
      compare two complex peptide mixtures with known peptide differences. This
      controlled experiment allowed us to assess the validity of each difference found
      and so to analyze the method's sensitivity and specificity. The method detects
      both presence versus absence and a 2-fold change in peptide concentration near
      the limit of detection of the instrument used, where chromatographic peaks may
      not be sufficiently well defined to be detected in individual samples. The method
      is more sensitive and gives fewer false positives than subtractive methods that
      ignore signal variability. Differential mass spectrometry combined with targeted
      MS/MS analysis of only identified differences may save both computation time and
      human effort compared to shotgun proteomics approaches.

PMID- 15481958
TI  - Structural characterization of N-glycopeptides by matrix-dependent selective
      fragmentation of MALDI-TOF/TOF tandem mass spectrometry.
AB  - The matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS
      technique described to date has proven to be a convenient and rapid method for
      identification and characterizations of proteins. However, the general MALDI-TOF
      MS analysis of complex carbohydrates and glycopeptides still entails special
      consideration of ionization and the fragmentation characteristics of labile
      carbohydrate moieties. In this study, an efficient and practical method we termed
      the matrix-dependent selective fragmentation (MDSF) technique of MALDI-TOF/TOF
      MS, which allows highly sensitive and reliable fragmentation of oligosaccharides
      and N-glycopeptides. Results from application of the MDSF technique to TOF/TOF MS
      analysis demonstrated that in comparison to the conventional postsource decay up
      to 170 times more sensitive product ion peaks could be obtained. It was also
      suggested that MDSF generates desired structural information based on the
      controlled cleavage of the singly charged precursor ion with different electronic
      excited states made by this method. Ideal product ion peaks observed by MDSF in
      TOF/TOF MS facilitated structural characterization of complex oligosaccharide
      derivatives including unstable Neu5Ac and Fuc residues and N-glycopeptides.

PMID- 15481959
TI  - Fullerene-functionalized gold nanoparticles: electrochemical and spectroscopic
      properties.
AB  - Fullerene (C(60))-tethered gold nanoparticles were synthesized by the coupling of
      the fullerene molecules with peripheral amine moieties on the particle surface.
      The particle composition was determined by thermogravimetric analysis and FT-IR
      spectroscopy. The resulting particles exhibited unique optical and
      electrochemical properties. UV-visible measurements showed that the C(60)
      characteristic absorption remained practically invariant whereas the fluorescence
      demonstrated rather drastic enhancement of emission efficiency as compared to the
      behaviors of C(60) monomers. Tethering of C(60) on the particle surface has
      virtually no effect on the particle molecular capacitance when C(60) is in
      neutral state, whereas when C60 is electroreduced, the particle effective
      capacitance increases drastically, reflected in the quantized capacitance
      charging measurements. The strong affinity of C(60) to amine moieties was also
      exploited to assemble multilayers of C(60) and gold particle nanocomposite
      structures. Quartz crystal microbalance measurements showed quite efficient
      adsorption of C(60) and particles up to two repeated cycles. However, the
      voltammetric responses of the surface-confined C(60) and gold particle composite
      structures were found to be complicated by the inaccessibility of electrolyte
      counterions due to the compact nature of the surface assemblies.

PMID- 15481960
TI  - Electrophoretic capture and detection of nanoparticles at the opening of a
      membrane pore using scanning electrochemical microscopy.
AB  - Stochastic electrophoretic capture of individual nanometer-scale particles at the
      small opening of a conically shaped nanopore in a synthetic membrane is
      described. Particle capture is sensed using a scanning electrochemical microscope
      (SECM) to measure the decrease in the transport rate of a redox-active molecule
      through the pore. The SECM tip is positioned at the larger backside opening of
      pore and used to amperometrically monitor the transport rate prior, during, and
      after particle capture. Following capture, the particle is released by
      electrophoretically driving it out of the pore opening and back into the
      solution. The capture and release method is demonstrated by detection of charged
      polystyrene spheres (43-150-nm diameter) using a polycarbonate membrane with
      conically shaped pores, the small opening of the pore having a diameter of 60 nm.
      The inverse of the time to capture polystyrene spheres increases with particle
      concentration over the range 10(8)-10(10) particles/mL. Selective detection based
      on nanoparticle charge and size is also demonstrated. A quantitative theoretical
      description of the rate of particle capture is presented, and the physical
      mechanism of particle capture, based on the balance of electrostatic and entropic
      forces, is considered.

PMID- 15481961
TI  - Palladium as a substrate for self-assembled monolayers used in biotechnology.
AB  - This paper describes self-assembled monolayers (SAMs) on palladium that resist
      the nonspecific adsorption of proteins and the adhesion of mammalian cells. These
      SAMs form when thin films of palladium are exposed to solutions of alkanethiol
      with the general structure HS(CH(2))(m)()(OCH(2)CH(2))(n)()OH (m = 2, 11; n = 3,
      6, 7). Ellipsometry and surface plasmon resonance spectroscopy (using a palladium
      on-gold substrate) showed that these SAMs resist adsorption of all proteins
      present in bovine serum. Microislands of SAMs of octadecanethiol on palladium
      allowed patterned adhesion and growth of mammalian cells (in a "sea" of
      oligo(ethyleneglycol)-terminated SAM). The oligo(ethyleneglycol)-terminated SAM
      resisted the invasion of cells for over four weeks under standard conditions of
      cell culture; similar SAMs on gold remained patterned for only two weeks.

PMID- 15481962
TI  - High resolution for single-strand conformation polymorphism analysis by capillary
      electrophoresis.
AB  - Since the successful completion of the Human Genome Project, increasing concern
      is being directed toward the polymorphic aspect of the genome and its clinical
      relevance. A form of single-strand DNA-conformation polymorphism analysis (SSCP)
      employing nondenaturing slab-gel electrophoresis (SGE) is applicable to the
      genetic diagnosis of bladder cancer from urine samples. To bring this technique
      into routine clinical practice, the use of capillary electrophoresis (CE) is
      naturally favorable in terms of speed and automation. However, the resolving
      power of SSCP, a prerequisite basis for reliability required in diagnostics,
      remains as a challenge for CE systems. We thus focused on this topic and
      conducted studies on CE instruments equipped with a single capillary or an array
      of multiple capillaries, using the resolution (Rs) as a quantitative scale for
      the resolving power. Polymer concentration and buffer are shown to be the
      decisive parameters. High Rs values of >2.5 are achieved for representative SNPs
      markers under the optimized conditions, without sacrificing such intrinsic
      advantages of CE over SGE as the 10-fold quicker migration time and operation
      that is reproducible, continuous, and automatic. The strategies presented broaden
      the limits of CE in both the current and related applications.

PMID- 15481963
TI  - Photoactivatable copolymers of vinylbenzyl thiocyanate as immobilization matrix
      for biochips.
AB  - Biochip surfaces for immobilization of DNA and proteins require reactive polymers
      with high immobilization capacity and low nonspecific binding. Most reactive
      surfaces consist of matrixes that provide epoxy, aldehyde, or amino functions for
      biomolecule binding. The most widely used oligonucleotide modification is a C6
      amino link. The high reactivity of isothiocyanate groups (NCS) toward amines was
      therefore the motivation to employ photogenerated NCS groups as binding sites for
      NH(2)-terminated oligonucleotides. Photosensitive poly(styrene-co-4-vinylbenzyl
      thiocyanate) (PST-co-VBT) was synthesized and applied as novel material for DNA
      and protein immobilization. The immobilization capacity of PST-co-VBT was a
      function of UV energy density used for photoactivation and was approximately 80%
      at 450 mJ cm(-)(2) (lambda(ex) = 254 nm). This surface was superior to tested
      commercial chip surfaces in signal-to-noise-ratio and reproducibility. Print
      buffer and spacer length were optimized for maximum fluorescence signal with DNA
      and proteins. UV exposure conditions and oligonucleotide modification were
      correlated, showing that this photochemical approach can be successfully applied
      for surface patterning of biochips.

PMID- 15481964
TI  - Single-cell chemical lysis in picoliter-scale closed volumes using a
      microfabricated device.
AB  - Investigating the intracellular contents of single cells is essential for
      understanding physiologic and pathologic processes at the cellular level. While
      existing protocols for cell lysis and sample preparation work well for larger
      samples, scaling to a single-cell level is challenging because of unavoidable
      analyte dilution and losses. Thus, we are proposing a microfabricated device for
      the controlled handling and mixing of picoliter cell suspension and lysis
      solution volumes. Cells and fluids are independently isolated in two
      microchambers of 25-pL volumes using the geometry of the microchannels and the
      coordinated action of four on-chip thermopneumatic actuators. Virtual walls
      formed by liquid-air interfaces in the hydrophobic capillary separate the two
      volumes, which are subsequently allowed to mix after drawing the air out of the
      capillary connecting the two microchambers. Following cell lysis, a limited and
      stable dilution of intracellular components is achieved, simplifying the
      requirements for subsequent analysis. Two assays at single-cell level, one for
      direct estimation of the intracellular concentration of a soluble dye and the
      other for indirect evaluation of intracellular quantities of insoluble actin,
      demonstrate the use of the microfabricated device for single-cell assays.

PMID- 15481965
TI  - Single color fluorescent indicators of protein phosphorylation for multicolor
      imaging of intracellular signal flow dynamics.
AB  - Existing monitoring methods for protein phosphorylation involved in intracellular
      signal transduction in vivo are exclusively based on fluorescence resonance
      energy transfer, which needs the measurement of the change in fluorescence
      intensities at two wavelengths. Therefore, it is difficult to monitor protein
      phosphorylation together with other related signaling processes, such as second
      messengers and protein translocation. To overcome this problem, we developed
      novel fluorescent indicators, each containing a differently colored (cyan and
      green) single fluorophore. The present indicator is a tandem fusion protein
      containing a kinase substrate domain, a circularly permuted fluorescent protein
      (cpFP), and a phosphorylation recognition domain. The cpFP is obtained by
      dividing a green fluorescent protein mutant (GFP) at residue 144-145 and linking
      the carboxy and amino portions thereof with a peptide linker. The substrate
      domain used in this study is a peptide sequence that is phosphorylated by insulin
      receptor. Phosphorylation of the substrate domain induces its interaction with
      the phosphorylation recognition domain, which causes a conformational change in
      the cpFP and a change in its fluorescence. The cyan and green indicators
      exhibited 10% decrease and 15% increase, respectively, in their fluorescence
      intensities upon phosphorylation. Using this cyan indicator and GFP-tagged
      mitogen-activated protein kinase (MAPK), we found that insulin-induced protein
      phosphorylation occurred immediately upon the addition of insulin, whereas
      nuclear translocation of MAPK occurred 7 min later. By tailoring the substrate
      domains and the phosphorylation recognition domains in these cyan and green
      indicators, the present approach should be applicable to the in vivo analysis of
      a broad range of protein phosphorylation processes, together with other
      intracellular signaling processes.

PMID- 15481966
TI  - A lipophilic sol-gel matrix for the development of a carbonate-selective
      electrode.
AB  - Organic-inorganic hybrid sol-gel matrixes were used as hosts for trifluoroacetyl
      p-decylbenzene (TFADB), a traditional ionophore for carbonate. The sol-gel
      precursor was prepared by the reaction of (3-isocyanopropyl)triethoxysilane with
      ethylene glycol. Hexadecyltrimethoxysilane (HDTMOS) was employed as a co
      precursor. An appropriate amount of tridodecylmethylammonium chloride (TDMAC) and
      2-nitrophenyloctyl ether (NPOE) were used as membrane components. On mixing with
      an acidic catalyst, the sol-state precursors slowly gelled, yielding a membrane
      in which the active components, TFADB and TDMAC, were encapsulated. Infrared,
      (1)H, and (29)Si MAS NMR spectrometers were employed to monitor the sol-gel
      process and the degree of polymerization. The performances of the sol-gel
      membrane-based electrodes were compared to those of TFADB-based poly(vinyl
      chloride) (PVC) membrane electrodes. Membranes with a molar ratio of TFADB:TDMAC
      (1:0.14) showed extended lifetime and stable baseline potential. The response
      slope toward carbonate was approximately 27 mV/decade between 10(-)(5) and 10(
      )(3.5) M at 18 degrees C. Interestingly, selectivity toward carbonate over
      salicylate and other lipophilic anions was improved, clearly deviating from the
      Hofmeister selectivity pattern. Responses toward small inorganic anions including
      chloride and sulfate were negligible. The selectivity coefficients measured by
      the matched potential method in 0.1 M tris-sulfuric acid buffer, pH 8.75, were
      log = -0.3, log = -4.2, and log = -2.5.

PMID- 15481967
TI  - A solid-phase microextraction device for the analysis of electrochemical reaction
      products by gas chromatography/mass spectrometry.
AB  - Presented is a solid-phase microextraction syringe-electrode assembly that may be
      used to identify electrode reaction products. After an electrochemical
      experiment, the electrode within this syringe-electrode assembly can be
      introduced into the injection port of a gas chromatograph. Electrochemical
      reaction products can be analyzed, provided they adhere to the electrode surface
      and are amenable to gas chromatographic/mass spectrometric analysis. We highlight
      the potential usefulness of this device using well-known electrochemical reaction
      of quinones.

PMID- 15481968
TI  - Multiplexed hybridization detection of quantum dot-conjugated DNA sequences using
      surface plasmon enhanced fluorescence microscopy and spectrometry.
AB  - In this study, the general suitability of quantum dot (QD)-DNA conjugates for the
      surface plasmon enhanced fluorescence spectroscopy technique is demonstrated.
      Furthermore, the QD-DNA system is transferred to the platform of surface plasmon
      enhanced fluorescence microscopy. Using this technique together with a microarray
      format, in which the sensor-bound single-stranded catcher probes are organized in
      individual surface spots, results in a simultaneous qualitative analysis of QD
      conjugated analyte DNA strands as multicolor images. A clear decomposition of
      different QD(x)()-DNA(y)() mixtures can be achieved for sequential, as well as
      mixture injections. Besides this, the study describes the successful approach of
      measuring spectrally resolved surface plasmon enhanced fluorescence signals
      derived from catcher probe hybridized QD-DNA conjugates.

PMID- 15481969
TI  - Preparation of steroid antibodies and parallel detection of multianabolic steroid
      abuse with conjugated hapten microarray.
AB  - A conjugated hapten microarray based on miniature immunoassay for fast and
      multiplex detection of anabolic steroids is reported for the first time. This
      preliminary study investigated the possibility of using a microarray technology
      as a multisteroid detection assay. The microarray system used eight monoclonal
      antibodies raised against three steroid conjugates, 4-androsten-4-chloro-17beta
      ol-3-one, 1,5alpha-androsten-1beta-methyl-17beta-ol-3-one, and 5beta-androsten-1
      en-17beta-ol-3-one, which were conjugated to BSA by the active ester method. In
      addition to 4 commercial conjugated haptens, 18 steroid-BSA conjugates were
      synthesized and from all these a conjugated hapten microarray was fabricated. The
      analyzed substances included 42 types of anabolic steroid reference materials and
      28 positive urine samples. Of these, 24 anabolic steroids and 12 positive urines
      were successfully detected.

PMID- 15481970
TI  - Fluorescent phenylpolyene analogues of the ether phospholipid edelfosine for the
      selective labeling of cancer cells.
AB  - Edelfosine (ET-18-OCH3), a synthetic antitumor ether lipid, is taken up by
      malignant but not by normal cells, triggering apoptosis in a large variety of
      human tumor cells. The synthesis of the first fluorescent edelfosine analogue
      (6), with apoptotic activity comparable to that of the parent drug, is described.
      Fluorescence microscopy experiments show that 6 selectively labels human cancer
      cells, accumulating into specific domains of the plasma membrane.

PMID- 15481971
TI  - HCV NS5b RNA-dependent RNA polymerase inhibitors: from alpha,gamma-diketoacids to
      4,5-dihydroxypyrimidine- or 3-methyl-5-hydroxypyrimidinonecarboxylic acids.
      Design and synthesis.
AB  - A new class of the HCV NS5b RNA-dependent RNA polymerase inhibitors, the
      dihyroxypyrimidinecarboxylic acid derivative, was designed from a diketoacid and
      meconic acid derivative discovered by screening. Mechanism of action and
      essential moieties required for activity were identified. The corresponding N
      methylpyrimidinone was also prepared; both classes are novel, reversible, and
      selective inhibitors of the HCV NS5b polymerase with improved druglike
      characteristics.

PMID- 15481972
TI  - Validation of model of cytochrome P450 2D6: an in silico tool for predicting
      metabolism and inhibition.
AB  - There has been much interest in the development of a predictive model of
      cytochrome P450 2D6 particularly because this enzyme is involved in the oxidation
      of at least 50 drugs. Previously we have described the combined use of homology
      modeling and molecular docking to correctly position a range of substrates in the
      CYP2D6 active site with the known sites of metabolism above the heme. Here, our
      approach identifies correctly the site of metabolism of the atypical (no basic
      nitrogen) cytochrome P450 2D6 substrate, spirosulfonamide. The same method is
      used to screen a small compound database for cytochrome P450 2D6 inhibition. A
      database containing 33 compounds from the National Cancer Institute database was
      docked into our cytochrome P450 2D6 homology model using the program GOLDv2.0.
      Experimental IC50 values for the 33 compounds were determined; comparison with
      the corresponding docked scores revealed a correlation with a regression
      coefficient of r2 = 0.61 (q2 = 0.59). The method was able to discriminate between
      tight and weak binding compounds and correctly identified several novel
      inhibitors. The results therefore suggest that our approach, which combines
      homology modeling with molecular docking, has produced a useful predictive in
      silico tool for cytochrome P450 2D6 inhibition, which is best used as one filter
      in a multifilter database screen.

PMID- 15481973
TI  - The anthrax protective antigen (PA63) bound conformation of a peptide inhibitor
      of the binding of lethal factor to PA63: as determined by trNOESY NMR and
      molecular modeling.
AB  - Anthrax protective antigen (PA) is one of the three proteins produced by the gram
      positive bacteria Bacillus anthracis collectively known as the "anthrax toxin"
      (Ascenzi, P.; Visca, P.; Ippolito, G.; Spallarossa, A.; Bolognesi, M.; et al.
      Anthrax toxin: a tripartite lethal combination. FEBS Lett. 2002, 531, 384-388).
      The role played by PA in anthrax intoxication is to transport the two enzymes
      lethal factor (LF) and edema factor (EF) into the cell. Collier and co-workers
      (Mourez, M.; Kane, R. S.; Mogridge, J.; Metallo, S.; Deschatelets, P.; et al.
      Designing a polyvalent inhibitor of anthrax toxin. Nat. Biotechnol. 2001, 958).
      reported the isolation of two peptides via phage display that bind to the PA63
      heptamer and inhibit its interaction with LF and EF, and thereby prevent the
      transport of LF and EF into the cell. One of these peptides, His-Thr-Ser-Thr-Try
      Trp-Trp-Leu-Asp-Gly-Ala-Pro (P1), was selected for structural investigation on
      the basis of its ability to prevent the binding of LF to the PA63 heptamer
      bundle. Two-dimensional trNOESY experiments coupled with NOE restrained simulated
      annealing calculations were used to determine the PA63-bound conformation of P1.
      On binding to PA63, P1 adopts a helical conformation involving residues 3-9 while
      the C- and N-terminal residues exhibit dynamic fraying.

PMID- 15481974
TI  - Second-generation lymphocyte function-associated antigen-1 inhibitors: 1H
      imidazo[1,2-alpha]imidazol-2-one derivatives.
AB  - A novel class of lymphocyte function-associated antigen-1 (LFA-1) inhibitors is
      described. Discovered during the process to improve the physicochemical and
      metabolic properties of BIRT377 (1, Figure 1), a previously reported hydantoin
      based LFA-1 inhibitor, these compounds are characterized by an imidazole-based
      5,5-bicyclic scaffold, the 1,3,3-trisubstituted 1H-imidazo[1,2-alpha]imidazol-2
      one (i.e. structure 3). The structure-activity relationship (SAR) shows that
      electron-withdrawing groups at C5 on the imidazole ring benefit potency and that
      oxygen-containing functional groups attached to a C5-sulfonyl or sulfonamide
      group further improve potency. This latter gain in potency is attributed to the
      interaction(s) of the functionalized sulfonyl/sulfonamide groups with the
      protein, likely polar-polar in nature, as suggested by SAR data. X-ray studies
      revealed that these bicyclic inhibitors bind to the I-domain of LFA-1 in a
      pattern similar to that of compound 1.

PMID- 15481975
TI  - Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity
      relationships for a novel class of antitumor agents.
AB  - Two closely related diaryl acylsulfonamides were recently reported as potent
      antitumor agents against a broad spectrum of human tumor xenografts (colon, lung,
      breast, ovary, and prostate) in nude mice. Especially intriguing was their
      activity against colorectal cancer xenografts. In this paper, rapid parallel
      synthesis along with traditional medicinal chemistry techniques were used to
      quickly delineate the structure-activity relationships of the substitution
      patterns in both phenyl rings of the acylsufonamide anti-proliferative scaffold.
      Although the molecular target of the compounds remains unclear, we determined
      that the vascular endothelial growth factor-dependent human umbilical vein
      endothelial cells assay in combination with a soft agar disk diffusion assay
      allowed for optimization of potency in the series. The pharmacokinetic properties
      and in vivo activity in an HCT116 xenograft model are reported for representative
      compounds.

PMID- 15481976
TI  - Successful virtual screening for a submicromolar antagonist of the neurokinin-1
      receptor based on a ligand-supported homology model.
AB  - The neurokinin-1 (NK1) receptor belongs to the family of G-protein-coupled
      receptors (GPCRs), which represents one of the most relevant target families in
      small-molecule drug design. In this paper, we describe a homology modeling of the
      NK1 receptor based on the high-resolution X-ray structure of rhodopsin and the
      successful virtual screening based on this protein model. The NK1 receptor model
      has been generated using our new MOBILE (modeling binding sites including ligand
      information explicitly) approach. Starting with preliminary homology models, it
      generates improved models of the protein binding pocket together with bound
      ligands. Ligand information is used as an integral part in the homology modeling
      process. For the construction of the NK1 receptor, antagonist CP-96345 was used
      to restrain the modeling. The quality of the obtained model was validated by
      probing its ability to accommodate additional known NK1 antagonists from
      structurally diverse classes. On the basis of the generated model and on the
      analysis of known NK1 antagonists, a pharmacophore model was deduced, which
      subsequently guided the 2D and 3D database search with UNITY. As a following
      step, the remaining hits were docked into the modeled binding pocket of the NK1
      receptor. Finally, seven compounds were selected for biochemical testing, from
      which one showed affinity in the submicromolar range. Our results suggest that
      ligand-supported homology models of GPCRs may be used as effective platforms for
      structure-based drug design.

PMID- 15481977
TI  - Architecture of P2Y nucleotide receptors: structural comparison based on sequence
      analysis, mutagenesis, and homology modeling.
AB  - Human P2Y receptors encompass at least eight subtypes of Class A G protein
      coupled receptors (GPCRs), responding to adenine and/or uracil nucleotides. Using
      a BLAST search against the Homo sapiens subset of the SWISS-PROT and TrEMBL
      databases, we identified 68 proteins showing high similarity to P2Y receptors. To
      address the problem of low sequence identity between rhodopsin and the P2Y
      receptors, we performed a multiple-sequence alignment of the retrieved proteins
      and the template bovine rhodopsin, combining manual identification of the
      transmembrane domains (TMs) with automatic techniques. The resulting phylogenetic
      tree delineated two distinct subgroups of P2Y receptors: Gq-coupled subtypes
      (e.g., P2Y1) and those coupled to Gi (e.g., P2Y12). On the basis of sequence
      comparison we mutated three Tyr residues of the putative P2Y1 binding pocket to
      Ala and Phe and characterized pharmacologically the mutant receptors expressed in
      COS-7 cells. The mutation of Y306 (7.35, site of a cationic residue in P2Y12) or
      Y203 in the second extracellular loop selectively decreased the affinity of the
      agonist 2-MeSADP, and the Y306F mutation also reduced antagonist (MRS2179)
      affinity by 5-fold. The Y273A (6.48) mutation precluded the receptor activation
      without a major effect on the ligand-binding affinities, but the Y273F mutant
      receptor still activated G proteins with full agonist affinity. Thus, we have
      identified new recognition elements to further define the P2Y1 binding site and
      related these to other P2Y receptor subtypes. Following sequence-based secondary
      structure prediction, we constructed complete models of all the human P2Y
      receptors by homology to rhodopsin. Ligand docking on P2Y1 and P2Y12 receptor
      models was guided by mutagenesis results, to identify the residues implicated in
      the binding process. Different sets of cationic residues in the two subgroups
      appeared to coordinate phosphate-bearing ligands. Within the P2Y1 subgroup these
      residues are R3.29, K/R6.55, and R7.39. Within the P2Y12 subgroup, the only
      residue in common with P2Y1 is R6.55, and the role of R3.29 in TM3 seems to be
      fulfilled by a Lys residue in EL2, whereas the R7.39 in TM7 seems to be
      substituted by K7.35. Thus, we have identified common and distinguishing features
      of P2Y receptor structure and have proposed modes of ligand binding for the two
      representative subtypes that already have well-developed ligands.

PMID- 15481978
TI  - Identification and specificity studies of small-molecule ligands for SH3 protein
      domains.
AB  - The Src Homology 3 (SH3) domains are small protein-protein interaction domains
      that bind proline-rich sequences and mediate a wide range of cell-signaling and
      other important biological processes. Since deregulated signaling pathways form
      the basis of many human diseases, the SH3 domains have been attractive targets
      for novel therapeutics. High-affinity ligands for SH3 domains have been designed;
      however, these have all been peptide-based and no examples of entirely nonpeptide
      SH3 ligands have previously been reported. Using the mouse Tec Kinase SH3 domain
      as a model system for structure-based ligand design, we have identified several
      simple heterocyclic compounds that selectively bind to the Tec SH3 domain. Using
      a combination of nuclear magnetic resonance chemical shift perturbation,
      structure-activity relationships, and site-directed mutagenesis, the binding of
      these compounds at the proline-rich peptide-binding site has been characterized.
      The most potent of these, 2-aminoquinoline, bound with Kd = 125 microM and was
      able to compete for binding with a proline-rich peptide. Synthesis of 6
      substituted-2-aminoquinolines resulted in ligands with up to 6-fold improved
      affinity over 2-aminoquinoline and enhanced specificity for the Tec SH3 domain.
      Therefore, 2-aminoquinolines may potentially be useful for the development of
      high affinity small molecule ligands for SH3 domains.

PMID- 15481979
TI  - A three-dimensional in silico pharmacophore model for inhibition of Plasmodium
      falciparum cyclin-dependent kinases and discovery of different classes of novel
      Pfmrk specific inhibitors.
AB  - The cell division cycle is regulated by a family of cyclin-dependent protein
      kinases (CDKs) that are functionally conserved among many eukaryotic species. The
      characterization of plasmodial CDKs has identified them as a leading antimalarial
      drug target in our laboratory. We have developed a three-dimensional QSAR
      pharmacophore model for inhibition of a Plasmodium falciparum CDK, known as
      Pfmrk, from a set of fifteen structurally diverse kinase inhibitors with a wide
      range of activity. The model was found to contain two hydrogen bond acceptor
      functions and two hydrophobic sites including one aromatic-ring hydrophobic site.
      Although the model was not developed from X-ray structural analysis of the known
      CDK2 structure, it is consistent with the structure-functional requirements for
      binding of the CDK inhibitors in the ATP binding pocket. Using the model as a
      template, a search of the in-house three-dimensional multiconformer database
      resulted in the discovery of sixteen potent Pfmrk inhibitors. The predicted
      inhibitory activities of some of these Pfmrk inhibitors from the molecular model
      agree exceptionally well with the experimental inhibitory values from the in
      vitro CDK assay.

PMID- 15481980
TI  - Antileishmanial pyrazolopyridine derivatives: synthesis and structure-activity
      relationship analysis.
AB  - Three series of 4-anilino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic esters were
      synthesized as part of a program to study potential anti-Leishmania drugs. These
      compounds were obtained by a condensation reaction of 4-chloro-1H-pyrazolo[3,4
      b]pyridine with several aniline derivatives. Some of them were also obtained by
      an alternative pathway involving a Mannich-type reaction. The hydrophobic
      parameter, log P, was determined by shake-flask methodology, and using the Hansch
      Fujita addictive hydrophobic fragmental constants. These compounds were tested
      against promastigote forms of Leishmania amazonensis. The very promising results
      showed the 3'-diethylaminomethyl-substituted compounds as the most active [IC50 =
      0.39 (21) and 0.12 microM (22)]. Molecular modeling, using semiempirical AM1
      method, predicted the most active compounds through the low-energy conformers
      superimposition on amodiaquine structure. QSAR equations, derived from the IC50
      values against L. amazonensis, showed the hydrophobic (log P) and Sterimol steric
      (L and B2) parameters as most significant contributions on biological activity.

PMID- 15481981
TI  - Influence of the linker in bispyridium compounds on the inhibition of human
      choline kinase.
AB  - Studies have been aimed to establish the structure-activity relationship that
      define choline kinase (ChoK) inhibitory potency and antiproliferative activity of
      a set of 25 bispyridinium compounds with electron-releasing groups at position 4.
      Here we report that, according to their inhibitory activities against human ChoK,
      the enzymatic inhibitory potency is closely related to the size of the linker,
      the 3,3'-biphenyl moiety being the most suitable. The N-methylanilino and its
      derivatives, 4-chloro-N-methylanilino and 3,5-dichloro-N-methylanilino, render
      higher ChoK inhibitory and antiproliferative activities against the HT-29 human
      colon cancer cell line.

PMID- 15481982
TI  - Inhibition of nucleoside transport by new analogues of 4-nitrobenzylthioinosine:
      replacement of the ribose moiety by substituted benzyl groups.
AB  - 4-Nitrobenzylthioinosine (NBTI, 1) is a well-known inhibitor for the nucleoside
      transport protein ENT1. However, its highly polar nature is unfavorable for oral
      absorption and/or penetration into the CNS. In the search for compounds with
      lower polarity than NBTI we replaced its ribose moiety by substituted benzyl
      groups. Halogen, hydroxyl, (trifluoro)methyl(-oxy), nitro, and amine
      functionalities were among the substituents at the benzyl group. In general,
      substitution of the benzyl group resulted in a lower affinity for ENT1. Only 2
      hydroxyl substitution showed a higher affinity. Most likely this is the result of
      hydrogen bonding. Substitution at the 2-position of the benzyl group with aryl
      groups was also addressed. Compared to parent compound carrying a 2-phenylbenzyl
      group, all synthesized analogues gave higher affinities. Introduction of fluoro,
      trifluoromethyl, methoxy, and hydroxyl groups at the phenyl group clearly showed
      that addition to the 4-position was preferable. Despite the highly different
      character of a ribose and a benzyl group, Ki values in the low nanomolar range
      were obtained for the benzyl-substituted derivatives. Compound 35, LUF5919, and
      compound 60, LUF5929, displayed the highest affinity (Ki = 39 nM for both
      compounds), having a polar surface area of 101 A2 and 85 A2, respectively.

PMID- 15481983
TI  - Novel 5-HT7 receptor inverse agonists. Synthesis and molecular modeling of
      arylpiperazine- and 1,2,3,4-tetrahydroisoquinoline-based arylsulfonamides.
AB  - A series of arylpiperazine- and 1,2,3,4-tetrahydroisoquinoline-based
      arylsulfonamides was synthesized and evaluated for their interactions with the
      constitutively active 5-HT7 receptor. Effects on basal adenylate cyclase activity
      were measured using HEK-293 cells expressing the rat 5-HT7. All ligands produced
      a decrease of adenylate cyclase activity, indicative of their inverse agonism.
      Additionally, computational studies with a set of 22 inverse agonists, including
      these novel inverse agonists and inverse agonists known from literature, resulted
      in a pharmacophore model and a CoMFA model (R2 = 0.97, SE = 0.18). Docking of
      inverse agonists at the binding site of a model of the helical parts of the 5-HT7
      receptor, based on the alpha carbon template for 7-TM GPCRs, revealed interesting
      molecular interactions and a possible explanation for observed structure-activity
      relationships.

PMID- 15481984
TI  - Design, synthesis, and evaluation of 3,4-dihydro-2H-[1,4]diazepino[6,7,1-hi]indol
      1-ones as inhibitors of poly(ADP-ribose) polymerase.
AB  - The design, synthesis, and biological evaluation of potent inhibitors of poly(ADP
      ribose) polymerase-1 (PARP-1) are reported. A novel series of 3,4-dihydro-2H
      [1,4]diazepino[6,7,1-hi]indol-1-ones were designed using a combination of protein
      structure-based drug design, molecular modeling, and structure-activity
      relationships (SAR). These novel submicromolar inhibitors possess a tricyclic
      ring system conformationally restricting the benzamide in the preferred cis
      orientation. The compounds were designed to optimize space-filling and atomic
      interactions within the NAD+ binding site of PARP-1. Previously described and
      newly adapted methods were applied to syntheses of these tricyclic inhibitors.
      Various modifications were made to the diazepinoindolones at the 6- and 7
      positions in order to study this region of the active site and optimize
      noncovalent interactions. The electron density of derivative 28 bound to chicken
      PARP-1 revealed that the oxime makes a tight hydrogen bond with the catalytic
      gamma-carboxylate of glutamic acid (Glu) 988 in accordance with our original
      designs and models. Most of the compounds have been evaluated for inhibition of
      human PARP-1. Selected inhibitors were also tested for the ability to potentiate
      the cytotoxic effect of the DNA-damaging agent Topotecan.

PMID- 15481985
TI  - 6-azapyrimidine-2'-deoxy-4'-thionucleosides: antiviral agents against TK+ and TK-
      HSV and VZV strains.
AB  - The synthesis of a series of novel 1-(2-deoxy-4-thio-beta-D-erythro
      pentofuranosyl)-(6-azapyrimidine) nucleosides is described. X-ray
      crystallographic data of the thymidine derivative allowed conformational
      analysis, which indicated a twist (3T2) sugar conformation. Hydrogen-bonded
      assemblies for the crystal structure were determined using PLATON software to
      allow further interpretation of the crystal packing and base interactions. The 6
      azapyrimidine nucleosides described were evaluated against a range of viral
      strains. The thymidine analogue showed pronounced activity against herpes simplex
      virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), and
      vaccinia virus. This compound lost only 5- to 10-fold of its antiviral activity
      against thymidine kinase (TK)-deficient HSV-1 and VZV strains. These observations
      suggest that the compounds may not entirely depend on viral TK-catalyzed
      phosphorylation for antiviral activity and/or use an alternative metabolic
      activation pathway, and/or display a unique mechanism of antiviral action by the
      unmetabolized nucleoside analogue.

PMID- 15481986
TI  - A docking score function for estimating ligand-protein interactions: application
      to acetylcholinesterase inhibition.
AB  - Acetylcholinesterase (AChE) inhibition is an important research topic because of
      its wide range of associated health implications. A receptor-specific scoring
      function was developed herein for predicting binding affinities for human AChE
      (huAChE) inhibitors. This method entails a statistically trained weighted sum of
      electrostatic and van der Waals (VDW) interactions between ligands and the
      receptor residues. Within the 53 ligand training set, a strong correlation was
      found (R2 = 0.89) between computed and experimental inhibition constants. Leave
      one-out cross-validation indicated high predictive power (Q2 = 0.72), and
      analysis of a separate 16-compound test set also produced very good correlation
      with experiment (R2 = 0.69). Scoring function analysis has permitted
      identification and characterization of important ligand-receptor interactions,
      producing a list of those residues making the most important electrostatic and
      VDW contributions within the main active site, gorge area, acyl binding pocket,
      and periferal site. These analyses are consistent with X-ray crystallographic and
      site-directed mutagenesis studies.

PMID- 15481987
TI  - 4-benzyl- and 4-benzoyl-3-dimethylaminopyridin-2(1H)-ones, a new family of potent
      anti-HIV agents: optimization and in vitro evaluation against clinically
      important HIV mutant strains.
AB  - The 4-benzyl and 4-benzoyl-3-dimethylaminopyridinones 13 and 14 are
      representatives of a new class of highly potent non nucleoside type inhibitors of
      HIV-1 reverse transcriptase. To conduct SAR studies on these two lead compounds,
      102 new analogues were prepared. Thirty-three compounds displayed nanomolar range
      activity in vitro against wild-type HIV-1, and among these, 18 were active
      against the 103N, Y181C, and Y188L mutant strains with IC50 values inferior to 1
      microM. Evaluation of this group of analogues against an additional eight single
      [100I, 101E, 106A, 138K, 179E, 190A, 190S, 227C] and four double HIV mutant
      strains [100I + 103N, 101E + 103N, 103N + 181C, and 227L + 106A], which are often
      present in HIV infected patients, permitted the selection of eight compounds,
      17x, 18b, 18c, 18f, 18g, 27, 30, and 42, which are globally more active than the
      lead molecules 13/14, emivirine and the currently used NNRTI, nevirapine. Further
      comparison of the 3'-CN-substituted benzoylpyridinone compound 18c, and the
      corresponding 3'-acrylonitrile-substituted analogue 30, to efavirenz, the
      reference molecule in anti-HIV therapy today, revealed that the pyridinone
      analogues displayed a superior inhibition profile in the in vitro cellular assay
      system. These results form a solid basis for continued optimization of the
      pyridinone series.

PMID- 15481988
TI  - Synthesis of analogues of Congo red and evaluation of their anti-prion activity.
AB  - No cure as of yet exists for any of the transmissible spongiform
      encephalopathies. In this paper, we describe the synthesis of analogues of Congo
      red and evaluation against a cellular model of infection, the SMB (scrapie mouse
      brain) persistently infected cell line, for their ability to inhibit the
      infectivity of the abnormal form of prion protein (PrP-res). The compounds have
      also been tested for their ability to inhibit the polymerization of PrPC by PrP
      res. A number of analogues showed inhibition of PrP-res infectivity at nanomolar
      concentrations. Several analogues show promise; the most active compound, 2a,
      inhibits the formation of PrP-res in SMB cells with an EC50 of 25-50 nM.

PMID- 15481990
TI  - A comparison of methods for modeling quantitative structure-activity
      relationships.
AB  - A large number of methods are available for modeling quantitative structure
      activity relationships (QSAR). We examine the predictive accuracy of several
      methods applied to data sets of inhibitors for angiotensin converting enzyme,
      acetylcholinesterase, benzodiazepine receptor, cyclooxygenase-2, dihydrofolate
      reductase, glycogen phosphorylase b, thermolysin, and thrombin. Descriptors
      calculated with CoMFA, CoMSIA, EVA, HQSAR, and traditional 2D and 2.5D
      descriptors were used for developing models with partial least squares (PLS). In
      addition, the genetic function approximation algorithm, genetic PLS, and back
      propagation neural networks were used for deriving models from 2.5D descriptors
      (i.e., 2D descriptors and 3D descriptors calculated from CORINA structures and
      Gasteiger-Marsili charges). Predictive accuracy was assessed using designed test
      sets. It was found that HQSAR generally performs as well as CoMFA and CoMSIA;
      other descriptor sets performed less well. When 2.5D descriptors were used, only
      neural network ensembles were found to be similarly or more predictive than PLS
      models. In addition, we show that many cross-validation procedures yield similar
      estimates of the interpolative accuracy of methods. However, the lack of
      correspondence between cross-validated and test set predictive accuracy for four
      sets underscores the benefit of using designed test sets.

PMID- 15481989
TI  - Synthesis and biological evaluation of novel N6-[4
      (substituted)sulfonamidophenylcarbamoyl]adenosine-5'-uronamides as A3 adenosine
      receptor agonists.
AB  - A new series of 1-deoxy-1-[(6-(4-(substituted
      aminosulfonyl)phenyl)amino)carbonylamino-9H-purin-9-yl]-N-ethyl-beta-D
      ribofuranuronamides (83-102) have been synthesized and tested at the human A3
      adenosine receptor subtype. All the derivatives described in this work displayed
      affinity versus this receptor in the nanomolar range and good selectivity versus
      A1 adenosine receptor subtype, confirming that the p-sulfonamido moiety
      positively affected the activity of the molecules. The best substituents at the
      sulfonamido nucleus were found to be small alkyl groups, like methyl, isopropyl,
      ethyl, or allyl moieties (compounds 96-100), whereas monosubstitution at the
      amino group led to a decrease in A3 affinity values. The selectivity versus A1
      adenosine receptor subtype is increased when the amino group in the sulfonamido
      core is represented by a hydrogenated heterocyclic ring like piperidine,
      morpholine, or pyrroline. Bulky groups, like adamantane and alkyl chains with
      more than four carbon atoms, are detrimental for the affinity and the selectivity
      of the A3 adenosine receptor agonists described here.

PMID- 15481991
TI  - Increased anti-P-glycoprotein activity of baicalein by alkylation on the A ring.
AB  - The aqueous extract of Scutellariae baicalensis Georgi has inhibitory activity
      against P-gp 170, a multiple drug resistant gene product. Baicalein, one of the
      major flavones, was found to be responsible for this activity. The hydroxyl
      groups of the A ring of baicalein were systematically alkylated in order to
      assess the effect of such modifications on the activity against P-gp 170. The
      impact of the baicalein modifications on activity against the growth of a human
      nasopharyngeal cancer cell line KB and its P-gp 170 overexpressing cell line
      KB/MDR were also examined. The results indicate that alkylation of R5 of
      baicalein does not have a major impact on the interaction with P-gp 170, whereas
      alkylation of R6 or R7 alone or both, could enhance the interaction of baicalein
      with P-gp 170 as well as the amount of intracellular accumulation of vinblastine,
      a surrogate marker for the activity of P-gp 170 pump of KB/MDR cells. In this
      case, the optimal linear alkyl functionality is a propyl side chain. These
      modifications could also alter the activity of compounds inhibiting cell growth.
      Among the different compounds synthesized, the most potent molecule against P-gp
      170 is 5-methoxy-6,7-dipropyloxyflavone (23). Its inhibitory activity against P
      gp 170 is approximately 40 times better, based on EC50 (concentration of the
      compound enhancing 50% of the intracellular vinblastine accumulation in the
      KB/MDR cells) and 3 times higher, based on Amax (the intracellular vinblastine
      accumulation of the KB/MDR cells caused by the compound) as compared to
      baicalein. Compound 23 is also a more selective inhibitor than baicalein against
      P-gp 170, because its cytotoxicity is less than that observed for baicalein. The
      growth inhibitory IC50 of compound 23 against KB and KB/MDR cells are about the
      same, suggesting that compound 23 is unlikely to be a substrate of P-gp 170 pump.
      Acetylation of R6, R7 or both could also decrease EC50 and increase Amax.
      Acetylated compounds are more toxic than baicalein, and their potency against
      cell growth is compromised by the presence of P-gp 170, suggesting that these
      compounds are substrates of P-gp 170. Benzylation of R6 or R7 but not both also
      enhanced anti-P-gp170 activity and potency against cell growth; however, the
      presence of P-gp 170 in cells did not have an impact on their sensitivity to
      these molecules, suggesting that the benzylated compounds are inhibitors but not
      substrates of P-gp 170, and perhaps have a different mechanism of action. In
      conclusion, the substitutions of R6 and R7 hydroxyl groups by alkoxy groups,
      acetoxy groups, or benzyloxy groups could yield compounds with different modes of
      action against P-gp 170 with different mechanisms of action against cell growth.

PMID- 15481992
TI  - Structure modifications of 6-aminoquinolones with potent anti-HIV activity.
AB  - We have recently discovered that 6-aminoquinolone derivatives could be valid
      leads for the development of new anti-HIV agents because of their new and
      diversified mode of action. In fact, studies carried out on the lead WM5 showed
      that this derivative is able to inhibit the Tat-mediated long terminal repeat
      driven transcription, an essential step in the HIV-1 replication cycle. Thus,
      starting from lead WM5, we performed the design and synthesis of an enlarged
      series of 6-aminoquinolones, which permitted some very potent anti-HIV 6-amino
      derivatives to be obtained and the structure-activity relationship to be
      delineated. Some derivatives, 26c, 26e, 26i, and 26j, proved to be highly
      effective in inhibiting HIV replication at 50% inhibitory concentration in the
      range of 0.0087-0.7 microg/mL in MT-4, PBMCs and CEM cell lines coupled with
      positive selectivity indexes that reach values higher than 1000 on CEM cell lines
      for compounds 26e and 26i. Time-of-addition experiments clearly confirm that the
      new, potent 6-aminoquinolones interact at a postintegration step in the
      replication cycle of HIV.

PMID- 15481993
TI  - New water-soluble sulfonylphosphoramidic acid derivatives of the COX-2 selective
      inhibitor cimicoxib. A novel approach to sulfonamide prodrugs.
AB  - The synthesis and pharmacological evaluation of new water-soluble phosphoramidate
      derivatives of the COX-2 selective inhibitor cimicoxib (4) are described. The
      sulfonylphosphoramidic acid derivative 10 was converted to 4 in human plasma and
      showed excellent in vivo activity in the rat carrageenan-edema test.
      Pharmacokinetic evaluation in dogs indicated that 10 behaved as a prodrug,
      immediately converting to 4 and giving an identical profile to that of the parent
      compound. These results represent the first description of phosphoramidic acids
      as prodrugs for the sulfonamido group. Compound 10 also exhibited an important
      and sustained analgesic effect in the hyperalgesia test in rats and a high
      aqueous solubility at pH higher than 7. This profile led to the selection of 10
      (UR-14048) for further development in the parenteral treatment of acute pain.

PMID- 15481994
TI  - Spectroscopic studies of diketoacids-metal interactions. A probing tool for the
      pharmacophoric intermetallic distance in the HIV-1 integrase active site.
AB  - The interactions with divalent cations of 4-phenyl-4-oxo-2-hydroxybuten-2-oic
      acid (benzoylpyruvic acid (BPA)), the pharmacophore of HIV-1 integrase
      inhibitors, were investigated using spectroscopic tools. In the absence of the
      enzyme, a 2:2 metal-ligand complex was characterized with an intermetallic
      distance of 4-6 A. Molecular modeling allowed us to propose a compatible
      structure for the metal-ligand complex. BPA does not inhibit the reactions
      catalyzed by HIV-1 IN, emphasizing the importance of the aromatic ring
      substitution in the antiviral activity.

PMID- 15481995
TI  - Evaluation of lactam-bridged neurotensin analogues adjusting psi(Pro10) close to
      the experimentally derived bioactive conformation of NT(8-13).
AB  - The neurotensin C-terminal hexapeptide, NT(8-13), which has been found to adopt a
      beta-strand-like conformation while bound to the NT1 receptor, was modified by
      the introduction of conformational constraints. Synthesis of the four
      stereoisomeric 4.4-spirolactams 1-4 and subsequent NT1 receptor binding studies
      showed that the restriction of psi(Pro10) to approximately 130 degrees leads to a
      more than 1000-fold increase of binding affinity for 1 (Ki = 12 nM) when compared
      to the more flexible analogue [NMeTyr11]NT(8-13).

PMID- 15481997
TI  - Therapeutic potential of oral antiproliferative agents in the prevention of
      coronary restenosis.
AB  - The treatment of coronary artery disease has reached many milestones - from
      balloon angioplasty to drug-eluting stents. The last decade witnessed the
      revolution of bare metal stents with new designs, alloys and strut thicknesses.
      Yet restenosis, the aphorismic 'Achilles heel', remains to be conquered. The
      restenosis rates with balloon angioplasty alone are 30-40% and are reduced to 20
      30% with stents. Although intravascular brachytherapy proved to be a durable and
      safely used technique to treat in-stent restenosis, clinical event rates were not
      reduced to single digits.Drug-eluting stents are showing positive results in this
      direction, but it is too early to predict their efficacy in various subsets of
      lesions. With the increased usage of these stents, there are reports of problems
      such as late stent malapposition, subacute and late thromboses, and aneurysm
      formations due to the vessel toxicity associated with this method of treatment.
      Furthermore, when multivessel stenting is considered, the cost of drug-eluting
      stents is a significant problem given the fact that these are no longer 'zero
      restenosis' devices. There is a definite need for a simple, safe and durable
      solution to restenosis. Oral agents are an alternative delivery strategy that can
      target multiple coronary lesions, which are targets for catheter-based
      revascularisation with any approved metal stent and with potentially lower cost.
      Although oral agents have been an interesting option to treat restenosis and
      several agents have been tested in trials since the 1980s, the results were
      disappointing. The development of devices such as intravascular ultrasound has
      led to a greater understanding of restenosis mechanisms, and the focus on
      pathophysiological mechanisms, which centred mainly on platelets, growth factors
      and lipids, has changed to inflammation, endothelium and smooth muscle cell
      proliferation.Accordingly, the targets of pharmaceutical agents have shifted from
      platelets to cell cycle inhibition, smooth muscle cell proliferation and
      migration, synthesis of extra cellular matrix, and inflammatory mediators.
      Initial encouraging results with oral drugs such as cilostazol, sirolimus
      (rapamycin) and thiazolidinediones indicate a definite place for this strategy to
      reduce restenosis. A desirable oral agent would be anti-inflammatory, inhibit
      smooth muscle cell migration and proliferation, promote endothelial growth, and
      be well tolerated and free from significant adverse effects. It may be useful to
      start with a high loading dose before stent implantation and then follow with a
      short-term lower maintenance dose. Future trials should be aimed at finding an
      ideal agent, effective loading dose, maintenance dose and optimum duration of
      therapy.

PMID- 15481998
TI  - Topical antibacterial therapy for acne vulgaris.
AB  - Topical antibiotics and benzoyl peroxide, are the two main topical antibacterial
      treatments indicated for mild-to-moderate acne vulgaris. Topical antibiotics act
      both as antibacterial agents suppressing Propionibacterium acnes in the sebaceous
      follicle and as anti-inflammatory agents. Benzoyl peroxide is a powerful
      antimicrobial agent that rapidly destroys both bacterial organisms and yeasts.
      Topical clindamycin and erythromycin have been proven to be effective against
      inflammatory acne vulgaris in concentrations of 1-4% with or without the addition
      of zinc. However, none of the antibacterials tested was more effective than
      benzoyl peroxide, which also has the advantage of not being associated with
      antimicrobial resistance. Topical antibacterial therapy should be discontinued
      once improvement is observed. If no improvement is observed within 6-8 weeks, the
      agent should be discontinued and a therapeutic switch considered. The primary
      limitation of benzoyl peroxide for some acne vulgaris patients is cutaneous
      irritation or dryness.Antibacterial therapy can be used in combination with other
      agents. Combining topical antibiotics and topical retinoids may enhance the
      efficacy, since the retinoid will improve the penetration of the antibiotic.
      Combining a topical antibiotic with benzoyl peroxide may increase the
      bactericidal effect of the antibiotic and reduce the potential for bacterial
      resistance. Topical and oral antibacterials should not be used in combination for
      the treatment of acne vulgaris, since this association may increase the risk of
      bacterial resistance.

PMID- 15481999
TI  - Management of acute and chronic gouty arthritis: present state-of-the-art.
AB  - There are three stages in the management of gout: (i) treating the acute attack;
      (ii) lowering excess stores of uric acid to prevent flares of gouty arthritis and
      to prevent tissue deposition of urate; and (iii) providing prophylaxis to prevent
      acute flares. It is important to distinguish between therapy to reduce acute
      inflammation in acute gout and therapy to manage hyperuricaemia in patients with
      chronic gouty arthritis. During the acute gouty attack nonpharmacological
      treatments such as topical ice and rest of the inflamed joint are useful. NSAIDs
      are the preferred treatment in acute gout. The most important determinant of
      therapeutic success is not which NSAID is chosen, but rather how soon NSAID
      therapy is initiated. Other treatments include oral and intravenous colchicine,
      intra-articular and systemic corticosteroids, and intramuscular corticotropin.
      Optimal treatment of chronic gout requires long-standing reduction in serum uric
      acid. The urate-lowering drugs used to treat chronic gout are the uricosuric
      drugs, the uricostatic drugs, which are xanthine oxidase inhibitors, and the
      uricolytic drugs. Xanthine oxidase inhibitors such as allopurinol, oxipurinol and
      febuxastat should be used as first-line treatment in patients with renal calculi,
      renal insufficiency, concomitant diuretic therapy and ciclosporin (cyclosporine)
      therapy, and urate overproduction. Uricosuric drugs include probenecid,
      benzbromarone, micronised fenofibrate and losartan. They are the urate-lowering
      drugs of choice in allopurinol-allergic patients and underexcretors with normal
      renal function and no history of urolithiasis. The use of recombinant urate
      oxidase in patients with chronic gout is limited by the need for parenteral
      administration, the potential antigenicity and production of anti-urate oxidase
      antibodies, and declining efficacy. The effectiveness of colchicine prophylaxis
      as an isolated therapy is still to be confirmed by placebo-controlled trials.
      Another issue is prophylaxis with NSAIDs. There are no comparative studies with
      colchicine.

PMID- 15482001
TI  - Trospium chloride in the management of overactive bladder.
AB  - Trospium chloride is an orally active, quaternary ammonium compound with
      antimuscarinic activity. It binds specifically and with high affinity to
      muscarinic receptors M(1), M(2) and M(3), but not nicotinic, cholinergic
      receptors. It is hydrophilic and does not cross the normal blood-brain barrier in
      significant amounts and, therefore, has minimal central anticholinergic activity.
      Peak plasma trospium chloride concentrations are attained approximately 5-6 hours
      after oral administration, which should occur before meals as concurrent food
      ingestion significantly reduces trospium bioavailability. Trospium chloride
      undergoes negligible metabolism by the hepatic cytochrome P450 system; few
      metabolic drug interactions are known. While trospium chloride dosage adjustments
      based on age or sex appear unwarranted, such adjustments may be needed in
      patients with severe renal impairment. Direct comparative studies in patients
      with overactive bladder indicate that trospium chloride is at least as effective
      as oxybutynin and tolterodine. Placebo-controlled studies have also confirmed the
      efficacy of trospium chloride in terms of improved urodynamic parameters; small
      scale, noncomparative studies have documented significant trospium chloride
      induced improvements in patients with reflex neurogenic bladder, postoperative
      bladder irritation and radiation-induced cystitis; and observational studies
      including >10,000 patients have also revealed favourable findings for trospium
      chloride, including a marked decrease in incontinence episodes and substantial
      improvement in health-related quality of life. Trospium chloride is generally
      well tolerated, and significantly more so than immediate-release oxybutynin. The
      most frequent adverse events, occurring in >1% of trospium chloride-treated
      patients, are dry mouth, dyspepsia, constipation, abdominal pain and nausea.
      Available for many years in several countries outside North America, trospium
      chloride is likely to develop an important role in the management of overactive
      bladder following its approval in the US on 28 May 2004.

PMID- 15482003
TI  - Progesterone treatment to prevent preterm birth.
AB  - The publication in 2003 of two large randomised trials of progesterone therapy to
      prevent preterm delivery has generated renewed interest in this treatment and has
      added substantial numbers of subjects to previously published small trials. The
      randomised trials of progestogens have generally shown efficacy in reducing the
      rate of recurrent preterm delivery in women with singleton pregnancies who were
      at high risk for preterm labour and delivery. Most of the successful trials have
      employed 17alpha-hydroxyprogesterone caproate, and one trial has reported
      positive results using progesterone vaginal suppositories. The administration of
      17alpha-hydroxyprogesterone caproate or progesterone suppositories to women with
      these high-risk pregnancies showed a significant protective effect for preterm
      birth in six of the seven published trials. No successful trials of progestogens
      have been reported for women at risk for preterm delivery because of multiple
      gestations. Trials of progestogens after the occurrence of symptoms of labour
      have shown them to be ineffective in prolonging pregnancy.

PMID- 15482000
TI  - Aspirin-induced asthma: clinical aspects, pathogenesis and management.
AB  - Aspirin (acetylsalicylic acid)-induced asthma (AIA) consists of the clinical
      triad of asthma, chronic rhinosinusitis with nasal polyps, and precipitation of
      asthma and rhinitis attacks in response to aspirin and other NSAIDs. The
      prevalence of the syndrome in the adult asthmatic populations is approximately 4
      10%. Respiratory disease in these patients may be aggressive and refractory to
      treatment. The aetiology of AIA is complex and not fully understood, but most
      evidence points towards an abnormality of arachidonic acid (AA) metabolism. Cyclo
      oxygenase (COX), the rate-limiting enzyme in AA metabolism, exists as two main
      isoforms. COX-1 is the constitutive enzyme responsible for synthesis of
      protective prostanoids, whereas COX-2 is induced under inflammatory conditions. A
      number of theories regarding its pathogenesis have been proposed. The shunting
      hypothesis proposes that inhibition of COX-1 shunts AA metabolism away from
      production of protective prostanoids and towards cysteinyl leukotriene (cys-LT)
      biosynthesis, resulting in bronchoconstriction and increased mucus production.
      The COX-2 hypothesis proposes that aspirin causes a structural change in COX-2
      that results in the generation of products of the lipoxygenase pathway. It is
      speculated that this may result in the formation of mediators that cause
      respiratory reactions in AIA. Related studies provide evidence for abnormal
      regulation of the lipoxygenase pathway, demonstrating elevated levels of cys-LTs
      in urine, sputum and peripheral blood, before and following aspirin challenge in
      AIA patients. These studies suggest that cys-LTs are continually and aggressively
      synthesised before exposure to aspirin and, during aspirin-induced reactions,
      acceleration of synthesis occurs. A genetic polymorphism of the LTC4S gene has
      been identified consisting of an A to C transversion 444 nucleotides upstream of
      the first codon, conferring a relative risk of AIA of 3.89. Furthermore, carriers
      of the C444 allele demonstrate a dramatic rise in urinary LTE(4) following
      aspirin provocation, and respond better to the cys-LT antagonist pranlukast than
      A444 homozygotes.AIA patients have an aggressive form of disease, and treatment
      should include combination therapy with inhaled corticosteroids, beta(2)
      adrenoceptor agonists and LT modifiers. Furthermore, recently developed
      inhibitors of COX-2 may be safer in patients with AIA.

PMID- 15482005
TI  - [The Venezuelan Association of Mycology and the Iberoamerican Journal of
      Mycology].

PMID- 15482002
TI  - Long-cycle treatment with oral contraceptives.
AB  - The conventional regimen of oral contraceptive (OC) use mimics the natural cycles
      by causing regular withdrawal bleeding, which can be avoided by omission of the
      hormone-free interval of 7 days. Consequently, long-cycle regimens with
      continuous administration of OCs for 3 or 6 months followed by a hormone-free
      interval of 7 days may reduce the frequency of menstruations and cycle-dependent
      complaints. Surveys have revealed that, despite a higher rate of irregular
      bleeding, the majority of women prefer the long-cycle regimen to the conventional
      OC regimen with regular bleeds every 4 weeks because it may improve quality of
      life. As this regimen increases the contraceptive efficacy to a large degree,
      continuous treatment with OCs may prevent unintended pregnancies in women who
      miss a pill or are concomitantly treated with drugs that are able to impair the
      efficacy of OCs. Postponement of withdrawal bleeding may also reduce or prevent
      menses-associated disorders such as hypermenorrhoea and dysmenorrhoea, and have
      beneficial effects in patients with haemorrhagic diathesis, endometriosis,
      uterine leiomyoma and polycystic ovary syndrome. Continuous use of OCs prevents
      the cyclic fluctuations of serum levels of ethinylestradiol and progestogen and,
      hence, the cyclic variations of metabolic serum parameters. Although the long
      cycle regimen is initially associated with an elevated rate of irregular
      bleeding, the total number of bleeding days that require sanitary product
      protection is lower than during conventional OC treatment. Many physicians tend
      to prescribe extended OC cycles for postponement of menstruation or reduction of
      frequency of regular bleeding. This review summarises and examines the available
      data on OC long-cycle regimens. The data suggest that the rate of treatment
      related side effects with OCs according to the long-cycle regimen is similar to
      that of conventional OC regimens. However, clinical trials are necessary to
      assess the impact of long-term OC long cycles on safety, particularly the risk of
      cancer and cardiovascular disease, and fertility after discontinuation of
      treatment.

PMID- 15482006
TI  - [A new generation of antifungal drugs].

PMID- 15482007
TI  - Differences in the Candida albicans antigenic expression after heat shock and
      infection.
AB  - Heat-shock and infection induce changes in protein expression in C. albicans. To
      investigate if these alterations induce changes in antigenicity, we have compared
      the reactivity mediated by IgA antibodies of protein extracts from a strain of C.
      albicans and the same strain recovered from an infected animal, both at 24
      degrees C and 37 degrees C. The antigenic variability was detected mainly in
      antigens recognized by salivary IgA. Antigens of 223, 205, 180 and 140 kDa were
      over-expressed in both strains at 37 degrees C, indicating that variations due to
      heat shock were present before and after infection. The antigens were
      characterized as mannoproteins located at the outer side of the cell wall. An
      antigen of 61 kDa was also detected in which the expression decreased
      significantly after infection This was independent of heat shock.

PMID- 15482004
TI  - Gefitinib: a review of its use in the management of advanced non-small-cell lung
      cancer.
AB  - Gefitinib (Iressa), the first commercially available epidermal growth factor
      receptor-tyrosine kinase (EGFR-TK) inhibitor, is indicated in the management of
      patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC).
      However, approved uses differ between countries; in most markets, gefitinib is
      approved for third-line use only (e.g. the US, Canada and Switzerland), although
      in some it is approved for both second- and third-line use (e.g. Japan and
      Australia) and, additionally, in patients considered unsuitable for chemotherapy
      (e.g. Indonesia and the Philippines). Few third-line treatment options exist for
      patients with inoperable advanced NSCLC who have failed both platinum-based and
      docetaxel chemotherapies. Gefitinib represents a significant advance in the
      treatment of this population; a once-daily, oral dosage of 250 mg/day was well
      tolerated, produced objective tumour responses and disease stabilisation, and
      improved disease-related symptoms and quality of life. It also produced overall
      survival outcomes that compared favourably with historical outcomes in a similar
      group of patients treated with three or four different chemotherapy regimens.
      These findings have been supported by observations from a global compassionate
      use programme. Ongoing or planned clinical trials are designed to confirm and/or
      further define the role of the drug in the above and other clinical settings.

PMID- 15482008
TI  - UV and X-ray sensitivity of Candida albicans laboratory strains and mutants
      having chromosomal alterations.
AB  - Utilization of L-sorbose, D-arabinose or primary fluconazole resistance in
      Candida albicans are controlled by copy number of specific chromosomes. On the
      other hand, spontaneous morphological mutants have a wide range of chromosomal
      alterations. We have investigated the UV and X-ray sensitivity of these mutants,
      as well as C. albicans laboratory strains. While L-sorbose utilizing mutants had
      normal sensitivities, a large subclass of D-arabinose utilizing mutants was
      abnormally sensitive to UV. Spontaneous morphological mutants responded
      differently, an expected result because of the heterogeneous nature of their
      electrophoretic karyotypes. We suggest that the differences in UV and X-ray
      sensitivity are due to gene imbalance caused by some chromosomal alterations. In
      this respect, the radiation sensitivity is similar to other features impaired by
      changes in chromosomes, but is unlike the acquisition of the ability to utilize
      alternative nutrients or the acquisition of resistance to fluconazole. Our
      studies also revealed that strains of C. albicans heterozygous for the mating
      type loci exhibited the same X-ray sensitivity as homozygous or hemizygous
      strains, a finding which is in contrast to the properties of Saccharomyces
      cerevisiae, where heterozygous strains are more resistant. This feature of C.
      albicans strains may be indicative of an inefficient repair system that may be
      related to inefficiency of mating.

PMID- 15482009
TI  - Cell surface hydrophobicity-associated adherence of Candida dubliniensis to human
      buccal epithelial cells.
AB  - Microbial adherence to mucosal surfaces is an important first step in the
      initiation of the pathogenic process in the oral cavity. Candida albicans, the
      most adherent and pathogenic Candida species, utilizes a variety of mechanisms to
      adhere to human tissues. Although the strongest mechanism of adherence involves
      mannoprotein adhesins on C. albicans, cell surface hydrophobicity (CSH) plays an
      important role in the adherence process by providing hydrophobic interactions
      that turn the initial attachment between the yeast and a surface into a strong
      bond. Recent cell wall analytical and comparative studies showed that, Candida
      dubliniensis, unlike C. albicans, possesses cell surface variations that allow it
      to be constantly hydrophobic, regardless of growth temperature. Based on these
      observations, the present study was designed to compare the adherence abilities
      of C. dubliniensis and C. albicans to pooled human buccal epithelial cells (BEC),
      in regards to their cell surface hydrophobicity. Ten C. albicans and nine C.
      dubliniensis isolates, as well as the C. albicans hydrophobic variant A9V10 were
      evaluated for adherence with BEC using visual aggregation in the wells of a
      microtiter plate and microscopic examination. All 11 C. albicans isolates failed
      to show adherence to BEC, visually or microscopically, when grown at 37 degrees
      C. The same isolates, however, showed significant increase in aggregation and
      microscopic adherence to BEC when grown at 25 degrees C. All C. dubliniensis
      isolates tested and the A9V10 C. albicans hydrophobic variant resulted in visual
      aggregation and adhered to BEC when grown at either temperature. The findings
      from this study show that, based on comparative adherence results and growth
      temperature changes, C. dubliniensis seems to have greater adherence to BEC than
      do typical C. albicans strains and that hydrophobic interactions seem to be the
      mechanism of adherence involved. Although many questions remain to be answered
      regarding the clinical implications of this observed in vitro enhanced adherence
      of C. dubliniensis to human BEC, these findings support the establishment of this
      novel species as a clinically significant yeast.

PMID- 15482010
TI  - [Evaluation of a new chromogenic medium (Candida ID) for the isolation and
      presumptive identification of Candida albicans and other medically important
      yeasts].
AB  - Candidiasis is a frequent human infection caused mainly by Candida albicans.
      However, other species are emerging as important pathogens, as Candida glabrata,
      Candida parapsilosis, Candida tropicalis, Candida krusei or Candida
      guilliermondii. Rapid identification of clinical isolates could facilitate
      diagnosis and treatment. Candida ID (bioMerieux, Spain) is a new medium for the
      isolation and presumptive identification of yeasts: C. albicans grows as blue
      colonies, and C. tropicalis, C. guilliermondii, Candida kefyr and Candida
      lusitaniae as pink ones. The utility of Candida ID was evaluated with more than
      700 clinical isolates and type culture collection strains from different genera
      including Candida, Cryptococcus, Saccharomyces, and Rhodotorula. Presumptive
      identification was confirmed by germ tube test, microscopic morphology and
      chlamydoconidia production on corn meal agar and carbohydrate assimilation on API
      ATB ID 32C or Vitek (bioMerieux). Growth on Candida ID was rapid (18-24 h) for
      most of the yeast strains tested. Sensitivity and specificity of identification
      of C. albicans was significantly high (>98%), since a very low number of isolates
      were found to be false negative or false positive. A better result was obtained
      for species growing as pink colonies (>99.5%). Detection of different species of
      medical important yeasts was easy with Candida ID, as perfectly distinct colors
      and textures of colonies were observed on this medium. Candida ID allowed the
      discrimination between C. glabrata (creamy and smooth) and C. krusei (rough and
      white) colonies. Other species showed different colony textures and colours,
      white being the predominant colour. Candida ID was very useful for the
      presumptive identification C. albicans isolates.

PMID- 15482011
TI  - [Pityriasis versicolor in Santo Domingo, Dominican Republic. In vivo
      morphological data of Malasezzia spp. in 100 cases].
AB  - BACKGROUND: Pityriasis versicolor is caused by Malassezia spp. It is a common
      world wide mycosis. Seven species are known of the Malassezia genus, and are
      identified in vitro by their morphological characteristics, biochemical tests and
      by molecular biology. OBJECTIVES: to determine clinical and epidemiological data
      of pityriasis versicolor as well as morphological aspects of Malassezia in vivo.
      METHODOLOGY: we performed a direct examination of the scales and classified the
      microscopic mycological elements as oval and orbicular spores, short and long
      hyphae. RESULTS: pityriasis versicolor mainly affected the thorax. Orbiculare
      yeasts and short hyphae frequently present. We could corroborate the wide
      morphological range of Malassezia spp. CONCLUSIONS: The morphological study of
      Malassezia spp. in vivo is not sufficient to determine the distribution of the
      various species.

PMID- 15482012
TI  - [The gas-liquid cromatography with mass spectrometry for the identification of
      yeasts].
AB  - Methods based on gas chromatography, have been used for identification of the
      yeasts. In order to know the value of the patterns obtained by this method, we
      have used this technique and mass spectrometry on 44 strains belonging to 16
      genus and 21 species of collection yeasts, identifying the corresponding peaks to
      22 fatty acids methyl esters by means of the reaction times of the corresponding
      standards and the confirmation of molecular weigh by mass spectrometry. The
      correlation coefficient was of 0.848965. The chromatographic technique seems of
      great utility for the determination of lipidotypes.

PMID- 15482013
TI  - Endophytic fungi from flowers, capsules and seeds of Eucalyptus globulus.
AB  - The main goal of this work was to detect whether Cytospora chrysosperma and
      Fusicoccum eucalypti are present as endophytes of symptomless hypocotyls,
      cotyledons, flowers, capsules, peduncles of flowers in order to interpret an
      earlier finding of their presence in seeds, seedling stems and twigs of E.
      globulus. Segments from these organs as well as from bark and the xylem from
      flower peduncles were surface-sterilized and plated on 2% malt-agar. All plates
      were incubated at 24 degrees C for six weeks or more depending on the growth rate
      of fungi. C. chrysosperma was asymptomatically present in flowers, capsules,
      hypocotyls, cotyledons and peduncles. F. eucalypti was isolated from asymptomatic
      flowers and capsules. It is probable that C. chrysosperma spreads during seed
      germination colonizing seedling stems through hypocotyl and cotyledon.

PMID- 15482014
TI  - Specific antibody response in a patient with Candida dubliniensis fungemia.
AB  - We report a case of fungemia caused by Candida dubliniensis in a non-HIV infected
      patient. Multiple cultures of blood performed over a period of 13 days were
      positive for this recently described yeast species. The C. dubliniensis isolates
      recovered were susceptible to fluconazole in vitro and the patient responded to
      intravenous therapy with this antifungal agent. It was possible to differentiate
      the fungemia caused by C. dubliniensis in this patient from that caused by C.
      albicans in other patients on the basis of the analysis of the antibody response
      since the C. dubliniensis-infected patient exhibited a characteristic and
      specific antibody response against a cell wall component of 160-170 kDa.

PMID- 15482016
TI  - Antibodies and fungi: an evolving paradigm with opportunities for the development
      of new antifungal therapies and vaccines.

PMID- 15482017
TI  - Mycology with molecular probes.

PMID- 15482018
TI  - Risk factors and physiopathology of candidiasis.
AB  - Recent epidemiological surveys have demonstrated an important increase in
      nosocomial infections among which Candida sp. plays an increasingly prominent
      role. Candida is now involved in about 10% of all septicemia and leads to a very
      high mortality rate in immunodepressed patients. Clinical studies show that any
      modification of the host immune status can facilitate the proliferation of
      endogenous Candida which, according to the importance of the immune deficiency,
      can provoke diseases ranging from benign localized mucocutaneous candidosis to
      sometimes lethal systemic invasions. The pathogenic behavior of Candida cells is
      mainly due to a very high phenotypic biodiversity. Following even very slight
      environmental modifications, it may change its behavior through the appearance of
      new or amplified properties such as tube formation, adherence, protease
      secretion, etc. Together with the impairment of host defenses, these new invasive
      properties lead to the so-called opportunistic pathogenicity of Candida cells.
      From a host point of view, after the integrity of surface teguments, the mucosal
      protection is ensured by the Th1 "cellular" immune response which, through pro
      inflammatory cytokine production, boosts the efficacy of the phagocytes
      (Polymorphonuclear cells and macrophages). Neutrophils are of particular
      importance as deep seated Candida proliferation is mostly associated with
      neutropenia. Whatever the pathogenic process, it is mostly due to modifications
      provoked by increasing medical awareness which makes patients more susceptible to
      illness. A better knowledge of the precise mechanisms involved and would lead to
      improved strategies for prevention.

PMID- 15482019
TI  - [Oral mycoses in the AIDS era].
AB  - The present advancement and generalization of oral mycosis is probably due to
      different factors associated to the progress and development of the countries and
      the presence of medically compromised patients and immunosupressor therapies.
      From all these mycoses, oral candidosis is the commonest, but histoplasmosis and
      paracoccidioidomycosis are also important. The main clinicopathologic and
      therapeutic features of those oral diseases are reviewed in this paper.

PMID- 15482020
TI  - Diagnosis of candidosis by amplification of small subunit of 18S rRNA gene.
AB  - A PCR assay for the diagnosis of infection produced by Candida sp. was developed.
      The primers, designated 520 and 522, were selected from highly-conserved areas of
      the small subunit (ssu) 18S rRNA gene of Candida spp. To check the value of the
      results a Candida albicans oligonucleotide probe, digoxigenin-labeled, and a
      general Candida probe were used in hybridization experiments with the amplified
      products. We were able to detect a Candida- specific fragment of 1800 bp from
      different clinical samples. The procedure described could provide an interesting
      complement to present diagnostic methods of detecting Candida sp in clinical
      samples.

PMID- 15482021
TI  - [Contribution to the study of dermatomycosis in Catalonia].
AB  - We report the results of a study which aim was the mycological identification of
      specimens coming from patients included in a clinical trial. A total of 445
      specimens from patients with clinical diagnosis of dermatomicosis were processed
      during 8 months (138 pityriasis versicolor, 28 cutaneous candidosis and 279
      dermatophytosis). A 48% of pityriasis versicolor cultures were positive for
      Malassezia furfur, 50% of candidosis cultures were positive for yeasts and 67% of
      dermatophytosis cultures were positive for dermatophytes. According to our
      results Candida albicans was the principal causative agent for cutaneous
      candidosis and Trichophyton mentagrophytes and Trichophyton rubrum were the most
      frequent isolated species causing dermatophytosis.

PMID- 15482022
TI  - [Variability in esterases of Metarhizium anisopliae].
AB  - The variability in esterases of the entomogenous fungus Metarhizium anisopliae
      was determined electrophoretically on 8.5% polyacrylamide gel. Ten isolates from
      diverse taxonomic groups of insects were analyzed. The electrophoretic analysis
      showed differences and similarities between these isolates and it was possible to
      distinguish six different patterns. The results obtained show a great
      polymorphism for the esterase system of M. anisopliae.

PMID- 15482023
TI  - [Madurella mycetomatis antigen for the serodiagnosis of mycetoma].
AB  - The aim of this work was to standardize metabolic and cytoplasmic Madurella
      mycetomatis antigen to be applied in the immunodiagnosis of mycetoma. Growth
      curves were established growing the mold in two broth media with weekly measures
      of protein and carbohydrate levels and of dry weight. Sera from immunized rabbits
      and patient's sera were used in immunoprecipitation to test the antigens. Three
      weeks old shaken cultures in Sabouraud broth at 37 degrees C were established as
      the optimal conditions to prepare cytoplasmic and metabolic antigens.
      Nevertheless, exoantigens were produced since the first week. Metabolic and
      cytoplasmic antigens presented cross reaction and by immunoblotting they shared
      33, 56 and 125 kDa molecular weight proteins. Preparation and use of the
      metabolic antigens is recommended for the immunodiagnosis of mycetoma when using
      the counterimmunoelectrophoresis technique.

PMID- 15482024
TI  - [First isolates of Cryptococcus neoformans var gattii in Spain].

PMID- 15482025
TI  - Multidetector CT angiography versus digital subtraction angiography for
      aortoiliac length measurements prior to endovascular AAA repair.
AB  - PURPOSE: To assess observer variation between calibrated-catheter digital
      subtraction angiography (DSA) and software-enhanced multidetector computed
      tomography angiography (CTA) in measuring vessel length prior to endovascular
      aortic aneurysm repair (EVAR). METHODS: Thirty patients (25 men; mean age 65
      years, range 61-85) scheduled for EVAR underwent CTA in 4x2-mm collimation using
      advanced vessel analysis software. CTA measurements were performed twice by 2
      blinded readers in random order with at least a 4-week interval between readings.
      Nine patients were found unsuitable for endovascular repair after the CTA, so DSA
      was performed in 21 patients for morphometric evaluation of the abdominal aorta
      and the iliac arteries. The following segments were measured: H1 (aneurysm neck),
      H2 (lower renal artery to distal aspect of the aneurysm), H3 (lower renal artery
      to aortic bifurcation), and H4a/H4b (lower renal artery to iliac bifurcations).
      Length measurements on DSA were made by (1) following the catheter path in the
      aortic lumen and (2) dividing tortuous vessel anatomy into segments and measuring
      each segment along an idealized centerline. Addition of the various segments
      allowed comparison with data obtained from CTA measurements. RESULTS: CTA was
      performed with good intraobserver agreement for all length parameters except H3
      in reader 2 (p<0.05). While good interobserver agreement was demonstrated for CTA
      over long aortoiliac distances (H4a, H4b), higher interobserver agreement was
      obtained with DSA for shorter segments (H1, H2). Considerable differences were
      observed between CTA and DSA for the lengths H2 and H4b. CONCLUSIONS: CTA
      produces better intra and interobserver correlations in measuring vessel length
      than DSA. It has the potential to replace DSA as an imaging method before EVAR.

PMID- 15482026
TI  - Stent-graft repair versus open surgery for the descending aorta: a case-control
      study.
AB  - PURPOSE: To compare the clinical outcomes of open surgery versus endovascular
      repair in patients with pathologies of the descending thoracic aorta (DTA).
      METHODS: This retrospective study included 44 patients (28 men; mean age 68+/-12
      years, range 37-86) treated for DTA pathologies between 1995 and 2003. Twenty-two
      patients (15 men; mean age 68+/-13 years, range 37-86) undergoing stent-graft
      implantation were matched for sex, age, emergency operation, and comorbidities
      (coronary artery disease, chronic obstructive pulmonary disease) with a 22
      patient contemporaneous surgical cohort (13 men; mean age 69+/-11 years, range 41
      80). RESULTS: Thirty-day mortality was 5% in the stent-graft group and 27% in the
      open surgery group (p=0.047). The incidences of postoperative stroke and
      paraplegia were both 5% in the stent-graft group and 9%, respectively, in the
      open surgery cohort. One patient required a second stent-graft due to an endoleak
      during the same hospital stay, and 2 reoperations were performed in the standard
      operation group (p = NS). Lengths of stay in the intensive care unit (ICU) and
      hospital were 4.3+/-5.4 and 11.9+/-15.0 days, respectively, in the stent-graft
      group and 10.0+/-7.4 and 21.5+/-17.4 days, respectively, in the open surgery
      group (p<0.006). CONCLUSIONS: Stent-graft repair was associated with lower 30-day
      mortality and comparable complication rates in older patients with significant
      comorbidities and a high percentage of emergency operations compared to open
      surgery. Stent-graft implantation shortens ICU and hospital stays significantly.
      In the future, subgroups of patients who may experience the greatest benefit from
      stent-graft repair in the long term should be defined.

PMID- 15482027
TI  - Transrenal fixation of aortic stent-grafts: current status and future directions.
AB  - Aortic stent-graft repair has been widely used in clinical practice for more than
      a decade, achieving satisfactory results compared to open surgical techniques.
      Transrenal fixation of stent-grafts is designed to obtain secure fixation of the
      proximal end of the stent-graft to avoid graft migration and to prevent type I
      endoleak. Unlike infrarenal deployment of stent-grafts, transrenal fixation takes
      advantage of the relative stability of the suprarenal aorta as a landing zone for
      the uncovered struts of the proximal stent. These transostial wires have sparked
      concern about the patency of the renal arteries, interference with renal blood
      flow, and effects on renal function. Although short to midterm results with
      suprarenal stent-grafts have not shown significant changes in renal function,
      long-term effects of this technique are still not fully understood. This review
      will explore the current status of transrenal fixation of aortic stent-grafts,
      potential risks of stent struts relative to the renal ostium, alternative methods
      to preserve blood flow to the renal arteries, and future directions or
      developments in stent-graft design to prevent myointimal proliferation around the
      stent struts.

PMID- 15482028
TI  - A novel technique of aortomonoiliac AAA repair in patients with a single patent
      iliac artery: a "stent-graft sandwich".
AB  - PURPOSE: To present a novel technique for endovascular repair of abdominal aortic
      aneurysms (AAA) in patients with an occluded iliac artery on one side. TECHNIQUE:
      In patients with an occluded iliac artery, the main body of a bifurcated modular
      endoprosthesis is deployed in standard fashion. Another stent-graft of a similar
      diameter is placed inside the deployed device so that the proximal end of the
      second endograft is a few millimeters caudal to the leading edge of the first
      device, which positions the second contralateral gate caudal to the flow divider
      of the first device. The second stent-graft is also rotated so that its
      contralateral gate is 180 degrees opposite to the contralateral gate of the first
      device. This "stent-graft sandwich" effectively mimics an aortomonoiliac device.
      After deployment of the second device, the attachment sites are dilated with
      appropriately sized balloons according to standard practice for the particular
      endoprostheses. CONCLUSIONS: Endovascular AAA repair utilizing a "stent-graft
      sandwich" technique is an effective method of treating AAAs when one iliac artery
      is occluded.

PMID- 15482029
TI  - Renal artery stenting using gadodiamide arteriography in patients with baseline
      renal insufficiency.
AB  - PURPOSE: To investigate whether a contrast agent containing gadodiamide can
      reduce the incidence of contrast-induced nephropathy associated with renal artery
      stenting in patients with preexisting renal insufficiency. METHODS: Between 1999
      and 2002, gadodiamide-based arteriography was used in 20 patients (12 men; mean
      age 69 years) with significant baseline renal insufficiency (creatinine > or =1.7
      mg/dL) undergoing renal artery stenting for > or =70% stenoses in 25 renal
      arteries. Baseline creatinine levels were compared to postprocedure and midterm
      follow-up levels. RESULTS: Procedural success was 100%. An average of 74 mL of
      gadodiamide contrast was used per case. Four patients received an additional 30
      mL (mean) of iodinated contrast due to poor image quality with gadodiamide alone.
      There was no significant change in mean creatinine levels at discharge (2.9
      mg/dL) compared to baseline (3.0 mg/dL, p=0.72). At midterm follow-up, mean
      creatinine levels (2.4 mg/dL) were significantly lower compared to baseline
      (p=0.004). CONCLUSIONS: Gadodiamide-based arteriography can be effectively used
      during RAS in patients with baseline renal insufficiency. This technique may
      enhance the renal-protective effect of renal artery stenting in this high-risk
      population with renal artery stenosis.

PMID- 15482030
TI  - Observations from multidetector CT imaging of different types of renal artery
      stents.
AB  - PURPOSE: To present an optimized protocol for acquisition and reconstruction of
      multidetector computed tomographic angiographic (CTA) images of the stents most
      commonly used in renal arteries. TECHNIQUE: CTA was performed on a 16-detector
      row CT scanner using 0.75-mm collimation. Multiplanar reformatted images
      perpendicular to the stents and 2-dimensional curved reformatted images were
      displayed. Two different view windows ("vascular" and "stent") were used, each
      adapted to the stent density, the vascular wall density, and the aortic
      enhancement. Five different types of stainless steel balloon-expandable stents
      were examined; all caused discernable artifacts. These artifacts became more
      prominent as the stent density increased, becoming most significant when 2 stents
      were positioned one inside the other. The "stent" window allowed better
      appreciation of the stent shape and its position compared to the aortic wall and
      ostial calcifications. The "vascular" window afforded a better view of the
      vascular lumen, in addition to visualizing the stent in several planes.
      CONCLUSIONS: Multidetector CTA using dedicated acquisition and reconstruction
      protocols is capable of visualizing the vascular lumen of different types of
      renal stents while avoiding metallic artifacts.

PMID- 15482031
TI  - Prospective randomized study comparing ultrasound-guided thrombin injection to
      compression in the treatment of femoral pseudoaneurysms.
AB  - PURPOSE: To compare in a randomized prospective study the treatment of femoral
      pseudoaneurysms with ultrasound-guided thrombin injection versus ultrasound
      guided compression. METHODS: Thirty consecutive patients (22 men; mean age 67+/-8
      years, range 53-82) with iatrogenic femoral pseudoaneurysms were randomized to
      treatment with either ultrasound-guided compression (n=15) or injection of bovine
      thrombin (n=15). The primary outcome measure was thrombosis of the pseudoaneurysm
      within 24 hours. Secondary outcome measures were complications and
      hospitalization time (LOS). RESULTS: Thrombosis within 24 hours was achieved in
      15 (100%) patients given thrombin versus 2 (13%) in the compression group
      (p<0.001). Of 13 pseudoaneurysms failing the initial compression treatment, 7
      were retreated, 4 successfully. Thus, only 6 (40%) lesions were thrombosed within
      48 hours after 1 or 2 compression sessions. The other 9 cases were successfully
      treated with thrombin injection. LOS was 2.8+/-1.5 days and 3.5+/-2.4 days in the
      thrombin and compression groups, respectively (p>0.05). No complications were
      noted in either group. CONCLUSIONS: Ultrasound-guided thrombin injection induces
      a fast, effective, and safe thrombosis of postcatheterization pseudoaneurysms.
      The technique is clearly superior to compression treatment and is recommended as
      the therapy of choice.

PMID- 15482032
TI  - Expanding false lumen in the abdominal aorta 5 years after endovascular repair of
      a type B aortic dissection: successful exclusion of 3 distal re-entry sites.
AB  - PURPOSE: To report endovascular treatment of an expanding aneurysmal false lumen
      several years after successful stent-graft deployment in the descending thoracic
      aorta for type B aortic dissection. CASE REPORT: A 54-year-old woman who had a
      stent-graft placed at the entry site of a type B aortic dissection 5 years prior
      presented with abdominal discomfort and palpable abdominal mass. Successful
      remodeling of the thoracic aorta was demonstrated by computed tomography;
      however, a false lumen aneurysm in the abdominal aorta had expanded from 4.8 to
      6.5 cm and caused symptoms. She was successfully treated with 3 additional stent
      grafts at 3 re-entry sites. Six months after the procedure, the false lumen
      aneurysm was completely excluded. CONCLUSIONS: Endovascular repair of the re
      entry sites can prevent further expansion of false lumen aneurysm, which occurs
      in some patients with type B dissection treated with stent-grafts.

PMID- 15482033
TI  - A longitudinal examination of male college students' perpetration of sexual
      assault.
AB  - Self-administered surveys were completed by 197 men in college at 2 time points,
      1 year apart. Men who committed sexual assault at multiple time points (repeat
      assaulters) had the most extreme scores on measures of hostility toward women,
      past sexual experiences, drinking in sexual situations, and adolescent
      delinquency. Nonassaulters had the least extreme scores and men who committed
      sexual assault at only 1 time point had scores that tended to fall in between.
      Repeat assaulters also expressed significantly less remorse when they described
      their sexual assault at Time 1 than did past assaulters who committed sexual
      assault only at the initial time point. These findings demonstrate the importance
      of initiating prevention and treatment programs in early adolescence, before
      longstanding attitudes and behaviors tolerant of sexual assault are established.

PMID- 15482034
TI  - Impact of executive function deficits and attention-deficit/hyperactivity
      disorder (ADHD) on academic outcomes in children.
AB  - The association between executive function deficits (EFDs) and functional
      outcomes were examined among children and adolescents with attention
      deficit/hyperactivity disorder (ADHD). Participants were children and adolescents
      with (n = 259) and without (n = 222) ADHD, as ascertained from pediatric and
      psychiatric clinics. The authors defined EFD as at least 2 executive function
      measures impaired. Significantly more children and adolescents with ADHD had EFDs
      than did control participants. ADHD with EFDs was associated with an increased
      risk for grade retention and a decrease in academic achievement relative to (a)
      ADHD alone, (b) controlled socioeconomic status, (c) learning disabilities, and
      (d) IQ. No differences were noted in social functioning or psychiatric
      comorbidity. Children and adolescents with ADHD and EFDs were found to be at high
      risk for significant impairments in academic functioning. These results support
      screening children with ADHD for EFDs to prevent academic failure.

PMID- 15482036
TI  - Interpersonal stressors and resources as predictors of parental adaptation
      following pediatric traumatic injury.
AB  - The authors examined the relationship of preinjury interpersonal resources and
      stressors to parental adaptation following pediatric traumatic brain injury (TBI)
      and orthopedic injury. Parents of children with severe TBI (n = 53), moderate TBI
      (n = 56), and orthopedic injuries (n = 80) were assessed soon after injury, 6 and
      12 months after the initial evaluation, and at an extended follow-up with a mean
      of 4 years postinjury. General linear model analyses provide support for both
      main and moderating effects of stressors and resources on parental adjustment.
      Support from friends and spouse was associated with less psychological distress,
      whereas family and spouse stressors were associated with greater distress. The
      results also reveal a marked decline in injury-related stress over follow-up for
      families in the severe TBI group who reported a combination of high stressors and
      high resources. The decline suggests that interpersonal resources attenuated long
      term family burden because of severe TBI. The findings are discussed in terms of
      their implications for intervention following TBI.

PMID- 15482035
TI  - Two-year stability and change of schizotypal, borderline, avoidant, and obsessive
      compulsive personality disorders.
AB  - The authors examined the stability of schizotypal (STPD), borderline (BPD),
      avoidant (AVPD) and obsessive-compulsive (OCPD) personality disorders (PDs) over
      2 years of prospective multiwave follow-up. Six hundred thirty-three participants
      recruited at 4 collaborating sites who met criteria for 1 or more of the 4 PDs or
      for major depressive disorder (MOD) without PD were assessed with semistructured
      interviews at baseline, 6, 12, and 24 months. Lifetable survival analyses
      revealed that the PD groups had slower time to remission than the MDD group.
      Categorically, PD remission rates range from 50% (AVPD) to 61% (STPD) for
      dropping below diagnostic threshold on a blind 24-month reassessment but range
      from 23% (STPD) to 38% (OCPD) for a more stringent definition of improvement.
      Dimensionally, these findings suggest that PDs may be characterized by
      maladaptive trait constellations that are stable in their structure (individual
      differences) but can change in severity or expression over time.

PMID- 15482037
TI  - Randomized controlled trial for behavioral smoking and weight control treatment:
      effect of concurrent versus sequential intervention.
AB  - The authors compared simultaneous versus sequential approaches to multiple health
      behavior change in diet, exercise, and cigarette smoking. Female regular smokers
      (N = 315) randomized to 3 conditions received 16 weeks of behavioral smoking
      treatment, quit smoking at Week 5, and were followed for 9 months after quit
      date. Weight management was omitted for control and was added to the 1st 8 weeks
      for early diet (ED) and the final 8 weeks for late diet (LD). ED lacked lasting
      effect on weight gain, whereas LD initially lacked but gradually acquired a
      weight-suppression effect that stabilized (p = .004). Behavioral weight control
      did not undermine smoking cessation and, when initiated after the smoking quit
      date, slowed the rate of weight gain, supporting a sequential approach.

PMID- 15482038
TI  - Efficacy and cost-effectiveness of a minimal intervention to prevent smoking
      relapse: dismantling the effects of amount of content versus contact.
AB  - Relapse prevention remains a major challenge to smoking cessation efforts. T. H.
      Brandon, B. N. Collins, L. M. Juliano, and A. B. Lazev (2000) found that a series
      of 8 empirically based relapse-prevention booklets mailed to ex-smokers over 1
      year significantly reduced relapse. This study dismantled 2 components of that
      intervention: the amount of content (number of booklets) and the frequency of
      contact. Content and contact were crossed in a 2 X 2 factorial design. The
      criteria of at least 1 week of abstinence at baseline was met by 431
      participants, 75%-85% of whom returned 12-, 18-, and 24-month follow-up
      questionnaires. Eight booklets produced consistently higher point-prevalence
      abstinence rates than did a single booklet, but frequency of contact did not
      affect outcome. Moreover, the high-content interventions were highly cost
      effective.

PMID- 15482039
TI  - Effectiveness of early screening for externalizing problems: issues of screening
      accuracy and utility.
AB  - Accurate, early screening is a prerequisite for indicated interventions intended
      to prevent development of externalizing disorders and delinquent behaviors. Using
      the Fast Track longitudinal sample of 396 children drawn from high-risk
      environments, the authors varied assumptions about base rates and examined
      effects of multiple-time-point and multiple-rater screening procedures. The
      authors also considered the practical import of various levels of screening
      accuracy in terms of true and false positive rates and their potential costs and
      benefits. Additional research is needed to determine true costs and benefits of
      early screening. However, the results indicate that 1st grade single- and
      multiple-rater screening models effectively predicted externalizing behavior and
      delinquent outcomes in 4th and 5th grades and that early screening is justified.

PMID- 15482040
TI  - Positive association of child involvement and treatment outcome within a manual
      based cognitive-behavioral treatment for children with anxiety.
AB  - Ratings of child involvement in manual-based cognitive-behavioral treatment for
      anxiety were associated with the absence of primary anxiety diagnosis and
      reductions in impairment ratings at posttreatment for 59 children with anxiety
      (ages 8-14 years). Good-to-excellent interrater reliability was established for
      the independent ratings of 237 therapy sessions, and strong psychometrics were
      established for the involvement measure. Child involvement at midtreatment, just
      prior to in vivo exposures, was positively associated with treatment gains but
      earlier involvement was not. Increased involvement during therapy (positive
      involvement shifts) may provide a useful index of change and may also predict
      outcomes. Involvement was not associated with client demographics or diagnostic
      category. Implications for treatment and measurement of psychotherapy process
      within manual-based treatments are discussed.

PMID- 15482041
TI  - Psychopathology and marital satisfaction: the importance of evaluating both
      partners.
AB  - Using path analysis and hierarchical linear modeling, the authors evaluated the
      associations between both partners' level of depression and anxiety, as measured
      by Minnesota Multiphasic Personality Inventory-2 (MMPI-2) content scales, and
      both partners' level of marital satisfaction among married couples (N = 774) that
      participated in the MMPI restandardization study. Results indicated that marital
      satisfaction was predicted by the person's own level of anxiety and depression
      (i.e., actor effects) and by his or her spouse's level of depression only (i.e.,
      partner effects). Findings also indicated that (a) there were no significant
      gender differences in the magnitude of effects, (b) depression effects were
      significantly stronger than anxiety effects, (c) actor effects were significantly
      stronger than partner effects, and (d) there were interactions between actor and
      partner effects for depression only.

PMID- 15482042
TI  - A randomized trial of long-term reinforcement of cocaine abstinence in methadone
      maintained patients who inject drugs.
AB  - This study determined whether long-term abstinence reinforcement could maintain
      cocaine abstinence throughout a year long period. Patients who injected drugs and
      used cocaine during methadone treatment (n = 78) were randomly assigned to 1 of 2
      abstinence-reinforcement groups or to a usual care control group. Participants in
      the 2 abstinence-reinforcement groups could earn take-home methadone doses for
      providing opiate- and cocaine-free urine samples; participants in 1 of those
      groups also could earn 5,800 US dollars in vouchers for providing cocaine-free
      urine samples over 52 weeks. Both abstinence-reinforcement interventions
      increased cocaine abstinence, but the addition of the voucher intervention
      resulted in the largest and most sustained abstinence. Therefore, voucher-based
      reinforcement of cocaine abstinence in methadone patients can be a highly
      effective maintenance intervention.

PMID- 15482043
TI  - Supporting families in a high-risk setting: proximal effects of the SAFEChildren
      preventive intervention.
AB  - Four hundred twenty-four families who resided in inner-city neighborhoods and had
      a child entering 1st grade were randomly assigned to a control condition or to a
      family-focused preventive intervention combined with academic tutoring.
      SAFEChildren, which was developed from a developmental-ecological perspective,
      emphasizes developmental tasks and community factors in understanding risk and
      prevention. Tracking of linear-growth trends through 6 months after intervention
      indicated an overall effect of increased academic performance and better parental
      involvement in school. High-risk families had additional benefits for parental
      monitoring, child-problem behaviors, and children's social competence. High-risk
      youth showed improvement in problem behaviors and social competence. Results
      support a family-focused intervention that addresses risk in low-income
      communities as managing abnormal challenges.

PMID- 15482044
TI  - Alcoholics anonymous and relapse prevention as maintenance strategies after
      conjoint behavioral alcohol treatment for men: 18-month outcomes.
AB  - Ninety men with alcohol problems and their female partners were randomly assigned
      to 1 of 3 outpatient conjoint treatments: alcohol behavioral couples therapy
      (ABCT), ABCT with relapse prevention techniques (RP/ABCT), or ABCT with
      interventions encouraging Alcoholics Anonymous (AA) involvement (AA/ABCT).
      Couples were followed for 18 months after treatment. Across the 3 treatments,
      drinkers who provided follow-up data maintained abstinence on almost 80% of days
      during follow-up, with no differences in drinking or marital happiness outcomes
      between groups. AA/ABCT participants attended AA meetings more often than ABCT or
      RP/ABCT participants, and their drinking outcomes were more strongly related to
      concurrent AA attendance. For the entire sample, AA attendance was positively
      related to abstinence during follow-up in both concurrent and time-lagged
      analyses. In the RP/ABCT treatment, attendance at posttreatment booster sessions
      was related to posttreatment abstinence. Across treatment conditions, marital
      happiness was related positively to abstinence in concurrent but not time-lagged
      analyses.

PMID- 15482045
TI  - Cognitive changes during prolonged exposure versus prolonged exposure plus
      cognitive restructuring in female assault survivors with posttraumatic stress
      disorder.
AB  - The authors report on changes in cognitions related to posttraumatic stress
      disorder (PTSD) among 54 female survivors of sexual and nonsexual assault with
      chronic PTSD who completed either prolonged exposure alone or in combination with
      cognitive restructuring. Treatment included 9-12 weekly sessions, and assessment
      was conducted at pretreatment, posttreatment, and a modal 12-month follow-up. As
      hypothesized, treatment that included prolonged exposure resulted in clinically
      significant, reliable, and lasting reductions in negative cognitions about self,
      world, and self-blame as measured by the Posttraumatic Cognitions Inventory. The
      hypothesis that the addition of cognitive restructuring would augment cognitive
      changes was not supported. Reductions in these negative cognitions were
      significantly related to reductions in PTSD symptoms. The addition of cognitive
      restructuring did not significantly augment the cognitive changes. Theoretical
      implications of the results are discussed.

PMID- 15482046
TI  - A functional approach to the assessment of self-mutilative behavior.
AB  - This study applied a functional approach to the assessment of self-mutilative
      behavior (SMB) among adolescent psychiatric inpatients. On the basis of past
      conceptualizations of different forms of self-injurious behavior, the authors
      hypothesized that SMB is performed because of the automatically reinforcing
      (i.e., reinforced by oneself; e.g., emotion regulation) and/or socially
      reinforcing (i.e., reinforced by others; e.g., attention, avoidance-escape)
      properties associated with such behaviors. Data were collected from 108
      adolescent psychiatric inpatients referred for self-injurious thoughts or
      behaviors. Adolescents reported engaging in SMB frequently, using multiple
      methods, and having an early age of onset. Moreover, the results supported the
      structural validity and reliability of the hypothesized functional model of SMB.
      Most adolescents engaged in SMB for automatic reinforcement, although a sizable
      portion endorsed social reinforcement functions as well. These findings have
      direct implications for the understanding, assessment, and treatment of SMB.

PMID- 15482047
TI  - Predictors of nonattendance of intake appointments among five Asian American
      client groups.
AB  - The authors examined the relationship of demographic, clinical, and service
      program factors with preintake attrition rates, or the nonattendance of intake
      appointments, among 5 Asian American groups at an ethnic-specific program. The
      results show that younger age, earlier appointment, Asian language match with the
      prescreening interviewer, and assignment of the prescreening interviewer as the
      intake therapist increased; however, gender match with prescreening interviewer
      decreased-the likelihood of intake attendance. As hypothesized, Southeast Asians
      (Cambodian, Iu Mien, and Vietnamese Americans to a lesser degree) reported higher
      intake attendance rates than more established East Asian groups (Chinese and
      Korean Americans). Specific implications of these results to program evaluation
      and to development and improvements in service delivery to Asian American groups
      are discussed.

PMID- 15482048
TI  - Physically abusive mothers' responses following episodes of child noncompliance
      and compliance.
AB  - The authors used sequential analysis to examine specific interaction patterns
      between physically abusive mothers and their children following episodes of
      noncompliance and compliance. Fifteen abusive and 15 nonabusive, low-risk mother
      child dyads were observed, and their behaviors were coded for specific
      interactions. The children in the study ranged in age from 2 to 6 years. Results
      indicated that after noncompliance occurred, physically abusive mothers were more
      likely than nonabusive mothers to respond negatively and give another command.
      When child compliance occurred, there were no group differences in the likelihood
      of praising their children's prosocial behavior, but physically abusive mothers
      were less likely than nonabusive mothers to engage in other forms of positive
      behavior (e.g., positive touch) after compliance. Clinical implications are
      discussed in the context of working with physically abusive families.

PMID- 15482049
TI  - Structure of anxiety and depression in urban youth: an examination of the
      tripartite model.
AB  - In this study, the authors examined the validity of the tripartite model of
      anxiety and depression in a community epidemiological sample of 467 urban African
      American youth. Participants completed the Baltimore How I Feel, a measure of
      anxiety and depressive symptoms, in Grades 6 and 9. Confirmatory factor analyses
      indicated that a 3-factor model representing the tripartite model fit the data
      well and better than competing models. Longitudinal confirmatory factor analysis
      revealed configural invariance of the tripartite factor structure. However, a
      predicted divergence among dimensions over time was not evidenced. High
      correlations among the tripartite dimensions suggest that anxiety and mood
      symptoms may not differentiate in urban youth. Results are discussed in terms of
      the ethnicity and urban context of this community sample.

PMID- 15482050
TI  - A longitudinal analysis of PTSD symptom course: delayed-onset PTSD in Somalia
      peacekeepers.
AB  - Posttraumatic stress disorder (PTSD) typically follows an acute to chronic
      course. However, some trauma victims do not report significant symptoms until a
      period of time has elapsed after the event. Although originally dismissed as an
      artifact of retrospective methodologies, recent prospective studies document
      apparent instances of delayed-onset PTSD. Little is known currently about factors
      associated with the delayed onset of PTSD. This study was designed to examine the
      course of PTSD in a sample of 1,040 U.S. military peacekeepers who served in
      Somalia. A small but nontrivial subset of participants endorsed clinically
      significant levels of PTSD after a period of minimal distress, the magnitude of
      which cannot be ascribed to minor waxing and waning of symptoms. War-zone
      exposure and perceived meaningfulness of the mission, as rated by soldiers after
      returning to the United States, predicted symptom course over the next 18 months.

PMID- 15482051
TI  - An interactive psychoeducational intervention for women at risk of developing an
      eating disorder.
AB  - This study evaluated a synchronous Internet-delivered intervention (chat room)
      for improving eating habits and body image in college-age women at risk for
      developing an eating disorder. Sixty at-risk women (mean age = 18.9, SD = 2.4;
      65.0% Caucasian, 19% Latino/Hispanic, 8% Asian/Pacific Islander, 3% African
      American, 5% other; mean body mass index = 25.6, SD = 5.7) were randomly assigned
      to intervention (n = 30) or control (n = 30) groups. Once a week for 8 weeks,
      participants used a private chat room for a 1-hr moderated discussion focused on
      improving body image and eating behaviors. Additional treatment components
      included psychoeducation, asynchronous support, homework, and summaries.
      Assessments were conducted at baseline, posttreatment, and 10 weeks after
      posttreatment. Participants indicated high satisfaction with the intervention
      mode. Intervention participants significantly reduced eating pathology and
      improved self-esteem over controls at follow-up. These findings suggest that
      synchronous, Internet-delivered programs are efficacious and have potential to
      reduce problematic attitudes and behaviors that may lead to eating disorders
      among college-age women.

PMID- 15482052
TI  - Inseminated female mice (Mus musculus) investigate rather than avoid novel males
      that disrupt pregnancy, but sires protect pregnancy.
AB  - Experiment 1 replicated the Bruce effect, showing pregnancy termination in CF1
      strain female mice (Mus musculus) housed underneath novel heterogeneous strain
      (HS) males. In a 4-arm maze in Experiment 2, inseminated CF1 females approached
      novel HS males more often than CF1 sires or unfamiliar CF1 males. In Experiment
      3, inseminated females showed random nesting sites when housed continuously
      underneath 4 compartments containing the sire, a novel CF1 male, a novel HS male,
      and no stimulus. In Experiment 4, when inseminated females were housed with or
      without the sire below novel HS males, the sire's presence decreased female
      interaction with novel males and mitigated the Bruce effect. Inseminated females
      do not reliably avoid males that disturb pregnancy unless the sire is immediately
      present.

PMID- 15482053
TI  - Clark's nutcrackers (Nucifraga columbiana) and the effects of goal--landmark
      distance on overshadowing.
AB  - Three groups of Clark's nutcrackers (Nucifraga columbiana) were trained to find a
      goal location defined by an array of 4 landmarks that varied in goal--landmark
      distance. The arrays for each group differed in the distance of the closest
      landmark and contained goal--landmark distances that were common across groups,
      allowing for the examination of the effects of both relative and absolute goal-
      landmark distance on encoding of a landmark array. All 3 groups readily learned
      the task and were subsequently tested in probe tests with only single landmarks
      from the array available. Search error in tests with single landmarks was
      compared both within and across groups. Results demonstrated that both relative
      and absolute goal-landmark distances are important in spatial search.

PMID- 15482054
TI  - Piagetian liquid conservation in the great apes (Pan paniscus, Pan troglodytes,
      and Pongo pygmaeus).
AB  - An understanding of Piagetian liquid conservation was investigated in 4 bonobos
      (Pan paniscus), 5 chimpanzees (Pan troglodytes), and 5 orangutans (Pongo
      pygmaeus). The apes were tested in the ability to track the larger of 2
      quantities of juice that had undergone various kinds of transformations. The
      accuracy of the apes' judgment depended on the shape or number of containers into
      which the larger quantity was transferred. The apes made their choice mainly on
      the basis of visual estimation but showed modest success when the quantities were
      occluded. The results suggest that the apes rely to a greater extent on visual
      information, although they might have some appreciation of the constancy of
      liquid quantities.

PMID- 15482055
TI  - Iberian rock lizards (Lacerta monticola) assess short-term changes in predation
      risk level when deciding refuge use.
AB  - Prey might assess that risk level estimated in the first encounter with a
      predator was fixed in subsequent responses, whereas prey using flexible behavior
      would track short-term changes in risk. The authors examined, in the field,
      refuge use of Iberian rock lizards (Lacerta monticola) after simulated predator
      attacks and tested (a) how risk was assessed when multiple sources of risk were
      present simultaneously, (b) how short-term changes in risk level of successive
      attacks affected refuge use, and (c) whether the interval between attacks was
      important, insofar as attacks were considered to be coming from the same or
      different predators. Results suggest that lizards have a flexible estimate of
      risk that is based on multiple sources and flexibly dependent on previous
      estimates.

PMID- 15482057
TI  - Detection of grouped and ungrouped parts in visual patterns by tufted capuchin
      monkeys (Cebus apella) and humans (Homo sapiens).
AB  - The authors investigated perceptual grouping in capuchin monkeys (Cebus apella)
      and humans (Homo sapiens). In Experiment 1, 6 monkeys received a visual pattern
      as the sample and had to identify the comparison stimulus featuring some of its
      parts. Performance was better for ungrouped parts than for grouped parts. In
      Experiment 2, the sample featured the parts, and the comparison stimuli, the
      complex figures: The advantage for ungrouped elements disappeared. In Experiment
      3, in which new stimuli were introduced, the results of the previous experiments
      were replicated. In Experiment 4, 128 humans were presented with the same tasks
      and stimuli used with monkeys. Their accuracy was higher for grouped parts.
      Results suggest that human and nonhuman primates use different modes of analyzing
      multicomponent patterns.

PMID- 15482056
TI  - Perceptual and acoustic evidence for species-level differences in meow
      vocalizations by domestic cats (Felis catus) and African wild cats (Felis
      silvestris lybica).
AB  - To test for possible anthropogenic selection effects on meows in domestic felids,
      vocalizations by domestic cats (Felis catus) were compared with cries by their
      closest wild relative, the African wild cat (Felis silvestris lybica).
      Comparisons included analysis of acoustic characteristics and perceptual studies
      with human (Homo sapiens) listeners. The perceptual studies obtained human
      listener ratings of call pleasantness. Both the acoustic and perceptual
      comparisons revealed clear species-level differences: The domestic cat meows were
      significantly shorter in mean duration than the wild cat meows, showed higher
      mean formant frequencies, and exhibited higher mean fundamental frequencies.
      Human listeners at all levels of experience and affinity for cats rated domestic
      cat meows as far more pleasant sounding than wild cat vocalizations. These
      results are consistent with a model of cat domestication that posits selective
      pressure on meows based on human perceptual biases.

PMID- 15482058
TI  - Nonenculturated orangutans' (Pongo pygmaeus) use of experimenter-given manual and
      facial cues in an object-choice task.
AB  - Several experiments have been performed, to examine whether nonhuman primates are
      able to make use of experimenter-given manual and facial (visual) cues to direct
      their attention to a baited object. Contrary to the performance of prosimians and
      monkeys, great apes repeatedly have shown task efficiency in experiments such as
      these. However, many great ape subjects used have been "enculturated"
      individuals. In the present study, 3 nonenculturated orangutans (Pongo pygmaeus)
      were tested for their ability to use experimenter-given pointing, gazing, and
      glancing cues in an object-choice task. All subjects readily made use of the
      pointing gesture. However, when subjects were left with only gazing or glancing
      cues, their performance deteriorated markedly, and they were not able to complete
      the task.

PMID- 15482059
TI  - Application of piecewise hierarchical linear growth modeling to the study of
      continuity in behavioral development of baboons (Papio hamadryas).
AB  - In behavioral science, developmental discontinuities are thought to arise when
      the association between an outcome measure and the underlying process changes
      over time. Sudden changes in behavior across time are often taken to indicate
      that a reorganization in the outcome-process relationship may have occurred. The
      authors proposed in this article the use of piecewise hierarchical linear growth
      modeling as a statistical methodology to search for discontinuities in behavioral
      development and illustrated its possibilities by applying 2-piece hierarchical
      linear models to the study of developmental trajectories of baboon (Papio
      hamadryas) mothers' behavior during their infants' 1st year of life. The authors
      provided empirical evidence that piecewise growth modeling can be used to
      determine whether abrupt changes in development trajectories are tied to changes
      in the underlying process.

PMID- 15482060
TI  - The precedence effect in three species of birds (Melopsittacus undulatus, Serinus
      canaria, and Taeniopygia guttata).
AB  - The perceived locations of paired auditory images, simulating direct sounds and
      their echoes, have been recently studied in budgerigars (Melopsittacus undulatus;
      M. L. Dent & R. J. Dooling, 2003a, 2003b). In this article, the authors extend
      those experiments to include measurements of the precedence effect using a
      discrimination paradigm in two additional bird species: canaries (Serinus
      canaria) and zebra finches (Taeniopygia guttata). Although time courses of
      summing localization, localization dominance, and echo thresholds were similar
      across all species, budgerigars had slightly higher overall levels of
      discrimination. The results from these experiments add further support that the
      precedence effect in birds is similar to that found in other animals and that the
      ability to suppress echoes that might degrade localization and auditory object
      perception may be a general property of the vertebrate auditory system.

PMID- 15482061
TI  - The relationship between dominance rank and spatial ability among male meadow
      voles (Microtus pennsylvanicus).
AB  - Males of many mammalian species exhibit contest competition and scramble
      competition for mates, but the relationship between these 2 forms of competition
      remains poorly understood. The authors measured dominance rank and spatial
      ability as traits likely to be selected by contest and scramble competition,
      respectively, among male meadow voles (Microtus pennsylvanicus). The spatial
      ability of males was assessed using water maze tests, and dominance rank was
      determined using paired trials in a neutral arena. Dominant males had better
      spatial-learning ability and tended to have quicker learning speed but did not
      have better spatial memory than less aggressive subordinates. Therefore, the
      authors found no evidence that contest and scramble competition have favored
      alternative reproductive phenotypes among male meadow voles.

PMID- 15482062
TI  - Behavioral and emotional response of Japanese macaque (Macaca fuscata) mothers
      after their offspring receive an aggression.
AB  - The authors of this study investigated the behavioral and emotional response of
      female Japanese macaques (Macaca fuscata) to an aggression received by their
      offspring to evaluate the existence of cognitive empathic responses in a
      naturalistic setting. After their offspring received an aggression, mothers did
      not direct increased affiliative contacts to them. The factors likely to affect
      the degree of distress in the offspring or the perceived risk for the mother
      failed to appropriately modulate maternal behavior. Finally, mothers did not
      increase their frequency of scratching (a behavioral indicator of anxiety) after
      their offspring had received an aggression. The results suggest Japanese macaque
      mothers may be unable to understand their offspring's need for distress
      alleviation after the receipt of aggression.

PMID- 15482063
TI  - Patterns of vocal sharing and social dynamics in a captive group of Campbell's
      monkeys (Cercopithecus campbelli campbelli).
AB  - Although vocal sharing is widespread at several phylogenetic levels, few
      descriptions concerned primates. The present study involved the dynamics of vocal
      structures and social organization in a captive group of Campbell's monkeys
      (Cercopithecus campbelli campbelli) at 3-year periods, using precise sound
      recording and comparison. The authors focused on combined harmonic 6 calls, often
      involved in vocal exchanges and associated with approaches. Each female produced
      1 to 4 variants, shared, or not, between individuals. Changes appeared between
      years in the form of disappearance, appearance, or transformation of variants.
      There was a decrease in the global degree of sharing over the years. Greater
      changes were observed after social disturbance. Sharing would be more important
      in disturbed than stable groups to advertise bonds.

PMID- 15482064
TI  - Linear theory, dimensional theory, and the face-inversion effect.
AB  - We contrast 2 theories within whose context problems are conceptualized and data
      interpreted. By traditional linear theory, a dependent variable is the sum of
      main-effect and interaction terms. By dimensional theory, independent variables
      yield values on internal dimensions that in turn determine performance. We frame
      our arguments within an investigation of the face-inversion effect--the greater
      processing disadvantage of inverting faces compared with non-faces. We report
      data from 3 simulations and 3 experiments wherein faces or non-faces are studied
      upright or inverted in a recognition procedure. The simulations demonstrate that
      (a) critical conclusions depend on which theory is used to interpret data and (b)
      dimensional theory is the more flexible and consistent in identifying underlying
      psychological structures, because dimensional theory subsumes linear theory as a
      special case. The experiments demonstrate that by dimensional theory, there is no
      face-inversion effect for unfamiliar faces but a clear face-inversion effect for
      celebrity faces.

PMID- 15482065
TI  - On Common Ground: Jost's (1897) law of forgetting and Ribot's (1881) law of
      retrograde amnesia.
AB  - T. Ribot's (1881) law of retrograde amnesia states that brain damage impairs
      recently formed memories to a greater extent than older memories, which is
      generally taken to imply that memories need time to consolidate. A. Jost's (1897)
      law of forgetting states that if 2 memories are of the same strength but
      different ages, the older will decay more slowly than the younger. The main
      theoretical implication of this venerable law has never been worked out, but it
      may be the same as that implied by Ribot's law. A consolidation interpretation of
      Jost's law implies an interference theory of forgetting that is altogether
      different from the cue-overload view that has dominated thinking in the field of
      psychology for decades.

PMID- 15482066
TI  - Forty-five years after Broadbent (1958): still no identification without
      attention.
AB  - According to D. E. Broadbent's (1958) selective filter theory, people do not
      process unattended stimuli beyond the analysis of basic physical properties. This
      theory was later rejected on the basis of numerous findings that people identify
      irrelevant (and supposedly unattended) stimuli. A careful review of this
      evidence, however, reveals strong reasons to doubt that these irrelevant stimuli
      were in fact unattended. This review exposed a clear need for new experiments
      with tight control over the locus of attention. The authors present 5 such
      experiments using a priming paradigm. When steps were taken to ensure that
      irrelevant stimuli were not attended, these stimuli produced no priming effects.
      Hence, the authors found no evidence that unattended stimuli can be identified.
      The results support a modern version of Broadbent's selective theory, updated to
      reflect recent research advances.

PMID- 15482067
TI  - A temporal model of level-invariant, tone-in-noise detection.
AB  - Level-invariant detection refers to findings that thresholds in tone-in-noise
      detection are unaffected by roving-level procedures that degrade energy cues.
      Such data are inconsistent with ideas that detection is based on the energy
      passed by an auditory filter. A hypothesis that detection is based on a level
      invariant temporal cue is advanced. Simulations of a leaky-integrator model,
      consisting of a bandpass filter, half-wave rectification, and a lowpass filter,
      account for thresholds in band-widening experiments. The decision variable is
      calculated from the discrete Fourier transform of the leaky-integrator output. A
      counterintuitive finding is the apparent disassociation of the phenomenon of
      critical bands estimated from band-widening experiments and the theory of
      auditory filters. Physiological plausibility is demonstrated by showing that a
      leaky integrator describes the discharge cadence of primary afferents for tone-in
      noise stimuli as well as for complex periodic sounds.

PMID- 15482068
TI  - The neural basis of error detection: conflict monitoring and the error-related
      negativity.
AB  - According to a recent theory, anterior cingulate cortex is sensitive to response
      conflict, the coactivation of mutually incompatible responses. The present
      research develops this theory to provide a new account of the error-related
      negativity (ERN), a scalp potential observed following errors. Connectionist
      simulations of response conflict in an attentional task demonstrated that the ERN
      -its timing and sensitivity to task parameters--can be explained in terms of the
      conflict theory. A new experiment confirmed predictions of this theory regarding
      the ERN and a second scalp potential, the N2, that is proposed to reflect
      conflict monitoring on correct response trials. Further analysis of the
      simulation data indicated that errors can be detected reliably on the basis of
      post-error conflict. It is concluded that the ERN can be explained in terms of
      response conflict and that monitoring for conflict may provide a simple mechanism
      for detecting errors.

PMID- 15482069
TI  - The native mind: biological categorization and reasoning in development and
      across cultures.
AB  - This article describes cross-cultural and developmental research on folk biology:
      that is, the study of how people conceptualize living kinds. The combination of a
      conceptual module for biology and cross-cultural comparison brings a new
      perspective to theories of categorization and reasoning. From the standpoint of
      cognitive psychology, the authors find that results gathered from standard
      populations in industrialized societies often fail to generalize to humanity at
      large. For example, similarity-driven typicality and diversity effects either are
      not found or pattern differently when one moves beyond undergraduates. From the
      perspective of folk biology, standard populations may yield misleading results
      because they represent examples of especially impoverished experience with
      nature. Certain phenomena are robust across populations, consistent with notions
      of a core module.

PMID- 15482070
TI  - "Scared stiff": catatonia as an evolutionary-based fear response.
AB  - Catatonia, long viewed as a motor disorder, may be better understood as a fear
      response, akin to the animal defense strategy tonic immobility (after G. G.
      Gallup & J. D. Maser, 1977). This proposal, consistent with K. L. Kahlbaum's
      (1874/1973) original conception, is based on similarities between catatonia and
      tonic immobility ("death feint") as well as evidence that catatonia is associated
      with anxiety and agitated depression and responds dramatically to
      benzodiazepines. It is argued that catatonia originally derived from ancestral
      encounters with carnivores whose predatory instincts were triggered by movement
      but is now inappropriately expressed in very different modern threat situations.
      Found in a wide range of psychiatric and serious medical conditions, catatonia
      may represent a common "end state" response to feelings of imminent doom and can
      serve as a template to understand other psychiatric disorders.

PMID- 15482071
TI  - A theory of interactive parallel processing: new capacity measures and
      predictions for a response time inequality series.
AB  - The authors present a theory of stochastic interactive parallel processing with
      special emphasis on channel interactions and their relation to system capacity.
      The approach is based both on linear systems theory augmented with stochastic
      elements and decisional operators and on a metatheory of parallel channels'
      dependencies that incorporates standard independent and coactive parallel models
      as special cases. The metatheory is applied to OR and AND experimental paradigms,
      and the authors establish new theorems relating response time performance in
      these designs to earlier and novel issues. One notable outcome is the remarkable
      processing efficiency associated with linear parallel-channel systems that
      include mutually positive interactions. The results may offer insight into
      perceptual and cognitive configural-holistic processing systems.

PMID- 15482072
TI  - An integrated theory of the mind.
AB  - Adaptive control of thought-rational (ACT-R; J. R. Anderson & C. Lebiere, 1998)
      has evolved into a theory that consists of multiple modules but also explains how
      these modules are integrated to produce coherent cognition. The perceptual-motor
      modules, the goal module, and the declarative memory module are presented as
      examples of specialized systems in ACT-R. These modules are associated with
      distinct cortical regions. These modules place chunks in buffers where they can
      be detected by a production system that responds to patterns of information in
      the buffers. At any point in time, a single production rule is selected to
      respond to the current pattern. Subsymbolic processes serve to guide the
      selection of rules to fire as well as the internal operations of some modules.
      Much of learning involves tuning of these subsymbolic processes. A number of
      simple and complex empirical examples are described to illustrate how these
      modules function singly and in concert.

PMID- 15482073
TI  - The concept of validity.
AB  - This article advances a simple conception of test validity: A test is valid for
      measuring an attribute if (a) the attribute exists and (b) variations in the
      attribute causally produce variation in the measurement outcomes. This conception
      is shown to diverge from current validity theory in several respects. In
      particular, the emphasis in the proposed conception is on ontology, reference,
      and causality, whereas current validity theory focuses on epistemology, meaning,
      and correlation. It is argued that the proposed conception is not only simpler
      but also theoretically superior to the position taken in the existing literature.
      Further, it has clear theoretical and practical implications for validation
      research. Most important, validation research must not be directed at the
      relation between the measured attribute and other attributes but at the processes
      that convey the effect of the measured attribute on the test scores.

PMID- 15482074
TI  - Population of linear experts: knowledge partitioning and function learning.
AB  - Knowledge partitioning is a theoretical construct holding that knowledge is not
      always integrated and homogeneous but may be separated into independent parcels
      containing mutually contradictory information. Knowledge partitioning has been
      observed in research on expertise, categorization, and function learning. This
      article presents a theory of function learning (the population of linear experts
      model--POLE) that assumes people partition their knowledge whenever they are
      presented with a complex task. The authors show that POLE is a general model of
      function learning that accommodates both benchmark results and recent data on
      knowledge partitioning. POLE also makes the counterintuitive prediction that a
      person's distribution of responses to repeated test stimuli should be multimodal.
      The authors report 3 experiments that support this prediction.

PMID- 15482075
TI  - Predicting drinking behavior and alcohol-related problems among fraternity and
      sorority members: examining the role of descriptive and injunctive norms.
AB  - The authors examined the relation between Greek students' perceptions of alcohol
      consumption in their pledge classes (descriptive norms) and acceptability of
      drinking (injunctive norms) and the ability of these normative influences to
      predict drinking behavior, alcohol-related negative consequences, and symptoms of
      alcohol dependence concurrently and prospectively over 1 year. Participants were
      279 men and 303 women recruited from incoming pledge classes of 12 fraternities
      and 6 sororities, who completed measures of descriptive and injunctive norms,
      alcohol use, and consequences. Results revealed that descriptive norms
      significantly predicted concurrent drinking. After controlling for baseline
      drinking, injunctive norms significantly predicted drinking 1 year later and
      predicted alcohol-related consequences and dependency symptoms at baseline and
      follow-up. The potential to incorporate injunctive norms into preventive
      interventions is discussed.

PMID- 15482076
TI  - Spiritual transcendence as a predictor of psychosocial outcome from an outpatient
      substance abuse program.
AB  - Does the Spiritual Transcendence Scale (STS; R. L. Piedmont, 1999) predict
      psychosocial outcomes from an outpatient substance abuse program? Self-report
      data on symptoms, personality, and coping resources were obtained for 73
      consecutive admissions (57 men and 16 women; ages 19-66 years) at intake and
      again from the 56 (47 men and 9 women) who completed treatment. Controlling for
      relevant demographic variables, pretreatment STS scores were significantly
      related to self-ratings at posttreatment. The STS predicted treatment outcomes
      over and above the contribution of the five-factor model of personality.
      Significant partial correlations between pretreatment STS scores and therapist
      ratings of treatment outcome were also obtained. Spiritual Transcendence,
      especially the facets of Universality and Connectedness, appears to play a
      significant role in substance abuse recovery.

PMID- 15482077
TI  - Sex on the internet: furthering our understanding of men with online sexual
      problems.
AB  - A survey on the MSNBC Web site identified 384 men as having online sexual
      problems (OSP). Respondents' reasons for online sexual activity (OSA) and their
      preferred Internet medium were associated with several online and offline
      consequences and behaviors, including important aspects of real-time
      relationships and sexual experimentation. Two broad behavior patterns manifested
      by men with OSP were identified: Men who use the Internet (a) to further their
      real-time sex lives and (b) as a substitute for their real-time sex lives. Men
      who facilitate their offline sex lives with the Internet might do so for any
      number of reasons, many of which are adaptive (e.g., sex education, to purchase
      sexual materials). Future research should use samples from a variety of affinity
      Web portals to further examine the factors that differentiate individuals who
      show no negative effects of OSA from those who do.

PMID- 15482078
TI  - Mood-induced increases in alcohol expectancy strength in internally motivated
      drinkers.
AB  - This study investigated whether exposure to musical mood induction procedures
      (MMIP) differentially increases the strength of specific alcohol expectancies for
      coping motivated (CM) versus enhancement motivated (EM) drinkers. Participants
      were 86 undergraduates who had elevated scores on either the CM or EM subscale of
      the Drinking Motives Questionnaire (M. L. Cooper, 1994). Participants were
      randomly assigned to either a positive or negative mood condition. The Alcohol
      Craving Questionnaire (E. G. Singleton, S. T. Tiffany, & J. E. Henningfield,
      1994) was administered at baseline and after MMIP to assess phasic changes in
      alcohol expectancy strength. Consistent with hypotheses, only CM drinkers in the
      negative mood condition reported increased relief expectancies, and only EM
      drinkers in the positive mood condition reported increased reward expectancies.
      Theoretical and clinical implications are discussed.

PMID- 15482079
TI  - Mediating and moderated effects of adolescent behavioral undercontrol and
      parenting in the prediction of drug use disorders in emerging adulthood.
AB  - This study tested whether the effects of parental alcoholism on drug use
      disorders in emerging adulthood were mediated by behavioral undercontrol and
      parenting in adolescence and whether parenting buffered the relation between
      undercontrol and drug use disorders. Participants were 175 children of alcoholics
      and 190 matched control participants from an ongoing longitudinal study (L.
      Chassin, F. Rogosch, & M. Barrera, 1991). Results showed that undercontrol and
      parental discipline mediated 58% of the effect of parental alcoholism on drug use
      disorders. The relation between behavioral undercontrol and drug use disorders
      was further moderated by parental support. This effect was "protective but
      reactive" (S. S. Luthar, D. Cicchetti, & B. Becker, 2000); at high levels of
      behavioral undercontrol the protective effect of parental support was lost.
      Highly undercontrolled adolescents may have such a strong diathesis for drug use
      disorders that buffers may not have the same effect as in those with better
      control.

PMID- 15482080
TI  - Transitions during effective treatment for cocaine-abusing homeless persons:
      establishing abstinence, lapse, and relapse, and reestablishing abstinence.
AB  - Data are reported on drug use among cocaine-dependent homeless persons who
      participated in a clinical trial that compared day treatment only (DT, n = 69)
      with day treatment plus abstinent-contingent housing and work (DT+, n = 72). Drug
      use was measured with multiple weekly urine toxicologies. Compared with DT
      participants, more DT+ participants established abstinence, maintained abstinence
      for longer durations, were marginally significantly more likely to lapse, and
      significantly less likely to relapse. Of all participants who established
      abstinence and then relapsed, DT+ participants relapsed later and were more
      likely to reestablish abstinence. These analyses yield information on the
      processes involved in the manner in which drug use changes as a result of
      abstinent-contingent housing and work.

PMID- 15482081
TI  - Effectiveness of community-based treatment for substance-abusing adolescents: 12
      month outcomes of youths entering phoenix academy or alternative probation
      dispositions.
AB  - Whereas strong efficacy research has been conducted on novel treatment approaches
      for adolescent substance abusers, little is known about the effectiveness of the
      substance abuse treatment approaches most commonly available to youths, their
      families, and referring agencies. This report compares the 12-month outcomes of
      adolescent probationers (N = 449) who received either Phoenix Academy, a
      therapeutic community for adolescents that uses a treatment model that is widely
      implemented across the U.S., or an alternative probation disposition. Across many
      pretreatment risk factors for relapse and recidivism, groups were well matched
      after case-mix adjustment. Repeated measures analyses of substance use,
      psychological functioning, and crime outcomes collected 3, 6, and 12 months after
      the baseline interview demonstrated that Phoenix Academy treatment is associated
      with superior substance use and psychological functioning outcomes over the
      period of observation. As one of the most rigorous evaluations of the
      effectiveness of a traditional community-based adolescent drug treatment program,
      this study provides evidence that one such program is effective. Implications of
      this finding for the dissemination of efficacious novel treatment approaches are
      discussed.

PMID- 15482082
TI  - Coping with distress by eating or drinking: role of trait urgency and
      expectancies.
AB  - The authors propose that trait urgency (the tendency to act rashly when
      distressed) is a risk factor for both alcohol abuse and bulimic symptoms, that
      disorder-specific expectancies influence whether one engages in one behavior or
      the other, and that expectancies moderate urgency's influence on those behaviors.
      Cross-sectional findings were consistent with the model. Problems from alcohol
      use were comorbid with binge eating and purging. Trait urgency was associated
      with both behaviors. Alcohol expectancies were associated with drinking levels
      and with problem drinking, but not with eating. Eating expectancies were
      associated with binge eating, but not with alcohol use or problems. Urgency's
      effect on binge eating was moderated by expectancies, but its effect on alcohol
      use and problem drinking was not.

PMID- 15482083
TI  - Reactivity to alcohol-related cues: relationship among cue type, motivational
      processes, and personality.
AB  - This study examined the relationship between personality traits implicated in the
      drinking literature (i.e., sensation seeking and anxiety) and reactivity to 2
      different alcohol cues. The opportunity to consume alcohol was manipulated, and
      differences in urge and affective reactivity were assessed. Gray's (1987) model
      of impulsive sensation seeking and anxiety was adopted to investigate
      relationships between personality and responses to the appetitive (consumption)
      and aversive (no consumption, nonrewarding) alcohol cues in 40 regular social
      drinkers. The consumption cue produced increases in appetitive motivation and
      positive correlations with sensation-seeking traits. The no-consumption cue
      produced increases in aversive motivation and positive correlations with anxiety
      related traits. It was concluded that Gray's model of impulsive sensation seeking
      and anxiety may provide a useful framework for examining the personality
      correlates of cue reactivity to different cues.

PMID- 15482084
TI  - Imagery-induced tobacco craving: duration and lack of assessment reactivity bias.
AB  - The duration of imagery-induced tobacco craving and whether craving responses are
      biased by repeated assessment (reactivity) was studied. Nonabstinent smokers (n =
      40) either imagined a scene describing smoking urges or rested. They then either
      completed the Tobacco Craving Questionnaire (TCQ; S. J. Heishman, E. G.
      Singleton, & E. T. Moolchan, 2003) every minute for 15 min or completed it after
      imagery or rest (Minute 1) and 15 min later. TCQ scores were greater after
      imagery compared with rest and remained significantly elevated at Minute 15.
      There was no evidence that TCQ responses were affected by repeated measurement.
      These data suggest that imagery-induced craving can persist for at least 15 min
      and that craving responses are not biased by assessment reactivity.

PMID- 15482085
TI  - Motivational enhancement therapy for nicotine dependence in methadone-maintained
      pregnant women.
AB  - Pregnant women who are dependent on nicotine and illicit substances are at
      especially high risk for health complications and psychosocial problems.
      Motivational enhancement therapy (MET) for reducing smoking during pregnancy was
      compared with standard-care practitioner advice in a 2-group randomized design.
      Participants were 63 pregnant opioid-dependent smokers seeking substance abuse
      treatment, methadone maintenance, and prenatal care. At a 10-week follow-up, self
      report and biological measures (i.e., CO, cotinine) indicated no differences in
      smoking between the MET and standard-care groups. However, MET participants were
      more likely to have moved forward on the stage of change continuum than those in
      standard care. Intensive treatment for nicotine dependence, environmental
      interventions, and innovative harm reduction strategies are recommended to
      address the barriers to quitting observed in this population of pregnant women.

PMID- 15482086
TI  - Brief motivational treatment for problem gambling: a 24-month follow-up.
AB  - A 24-month follow-up of a randomized clinical trial of 2 brief treatments for
      problem gambling (N = 67) revealed an advantage for participants who received a
      motivational telephone intervention plus a self-help workbook compared with
      participants who received only the workbook. Although the 2 groups did not differ
      in the number of participants reporting 6 months of abstinence, the motivational
      intervention group gambled fewer days, lost less money, and had lower South Oaks
      Gambling Screen scores. They were more likely to be categorized as improved
      compared with the self-help workbook only group. Overall, the results support the
      effectiveness of a brief telephone- and mail-based treatment for problem
      gamblers.

PMID- 15482087
TI  - Nurse safety: have we addressed the risks?

PMID- 15482088
TI  - Caring for those who care: a tribute to nurses and their safety.
AB  - From the clinics of South Africa, where there are "No Gun" signs on the walls; to
      the rural island hospital in Micronesia, where there is no running water; to the
      urban hospitals of Los Angeles serving non-English speaking clients from around
      the globe; to the nurse-run clinics in the harsh Alaska frontier, nurses are
      focused on doing their best to give quality nursing care. This focus on providing
      quality care is commendable. However, nurses must also focus on taking care of
      themselves so they are able both to continue providing quality care for their
      patients and to maintain the profession's ability to recruit and retain new
      nurses. In nursing textbooks from the late 1980s and early 1990s, risks to health
      care workers were listed only as sub headings in sections such as infectious
      agents and musculoskeletal injuries, or in general chapters on "women's work." It
      is a remarkable sign of progress that there is now a discrete focus on the health
      and safety of health care workers. This article provides a general introduction
      to the topic of nurse safety. First the major areas of health and safety concerns
      and the Hierarchy of Controls framework for risk reduction will be outlined.
      Next, findings from American Nurses Association (ANA) surveys which helped to
      crystallize the issue of safety and challenged the profession to focus on nurse
      safety will be presented. Following this, the linkages between patient safety and
      nurse safety will be discussed. Finally national reports, environmental
      initiatives, and policy successes and opportunities related to nurse safety will
      be noted.

PMID- 15482089
TI  - Handle with care: The American Nurses Association's Campaign to address work
      related musculoskeletal disorders.
AB  - In response to the significant number and severity of work-related back injuries
      and other musculoskeletal disorders among nurses, the American Nurses Association
      (ANA) has launched the Handle With Care campaign. The campaign seeks to build a
      health care industry-wide effort to prevent back and other musculoskeletal
      injuries. This is being done through developing partnerships and coalitions,
      education and training, increasing use of assistive equipment and patient
      handling devices, reshaping nursing education to incorporate safe patient
      handling, and pursuing federal and state ergonomics policy by highlighting
      technology-oriented safe-patient handling benefits for patients and nurses. In
      the absence of ergonomics regulations at national or state levels that protect
      health care workers, ANA has taken on alternative approaches to encourage a
      movement to control ergonomic hazards in the health care workplace and prevent
      back injuries among the nation's nursing workforce.

PMID- 15482090
TI  - Evidence-based practices for safe patient handling and movement.
AB  - Efforts to reduce injuries associated with patient handling are often based on
      tradition and personal experience rather than scientific evidence. The purpose of
      this article is to summarize current evidence for interventions designed to
      reduce caregiver injuries, a significant problem for decades. Despite strong
      evidence, published over three decades, the most commonly used strategies have
      strong evidence that demonstrate they are ineffective. There is a growing body of
      evidence to support newer interventions that are effective or show promise in
      reducing musculoskeletal pain and injuries in care providers. The authors have
      organized potential solutions into three established ergonomic solution types:
      engineering based, administrative, and behavioral. For each intervention, the
      level of evidence to support its use is provided.

PMID- 15482091
TI  - Needlestick and sharps injury prevention.
AB  - Every day while caring for patients, nurses are at risk to exposure to bloodborne
      pathogens potentially resulting in infections such as HIV or hepatitis B and C.
      These exposures, while preventable, are often accepted as being a part of the
      job. In the United States, needlestick injuries have begun to decrease from an
      estimated one million exposures per year in 1996 to 385,000 per year in 2000.
      This decline has resulted from the protections afforded by the Occupational
      Safety and Health Administration's (OSHA) Bloodborne Pathogens Standard. Reasons
      for the success in decreasing needlestick and sharps injuries may be attributed
      to the elimination of needle recapping and the use of safer needle devices,
      sharps collection boxes, gloves and personal protective gear, and universal
      precautions. The prevention of needlestick injuries has made slow progress over
      the past 20 years since the HIV epidemic drew attention to the deadly nature of
      health care work and to protection of health care worker health and safety. In
      Africa, where the AIDS virus originated and where the prevalence of the human
      immunodeficiency virus (HIV) among hospitalized patients is highest in the world,
      attention has been directed only recently at protecting health care workers.
      Nurses, especially those infected from a preventable exposure, have been at the
      forefront of advocacy for prevention. This article includes a review about the
      hazard of exposure to bloodborne pathogens and epidemiology of occupational
      infection. The author discusses how to apply standard methods of occupational
      health and industry hygiene using the hierarchy of controls framework to prevent
      exposure to blood, and discusses evidence-based prevention and efficacy of
      particular control measures. Legislative progress and implementation of
      enforceable policy to protect health care workers is outlined.

PMID- 15482092
TI  - Safe handling of hazardous drugs.
AB  - Recommendations for the safe handling of hazardous drugs have been available for
      more than twenty years. Evidence for continued risk of occupational exposure is
      abundant; however, nurses' use of the recommended precautions is not universal.
      This may be related to a lack of information or to a lack of serious concern for
      the potential hazards. This article includes a discussion of current issues
      related to handling hazardous drugs in the workplace and a review of the history
      of safe handling guidelines, current recommendations, and barriers to
      implementing guidelines in health care settings.

PMID- 15482093
TI  - Workplace violence in health care: recognized but not regulated.
AB  - Workplace violence is one of the most complex and dangerous occupational hazards
      facing nurses working in today's health care environment. This article includes
      critiques of the conceptual, empirical, and policy progress of the past decade, a
      discussion of the need for methodologically rigorous intervention effectiveness
      research, and a description of a joint-labor management research effort aimed at
      documenting a process to reduce violence in a state mental health system. The
      development of a typology of workplace violence has advanced our understanding of
      the relationship of the perpetrator of the violence to the victim and provided a
      foundation for conceptual frameworks linking etiology and prevention. Even though
      health care workers may be exposed to four types of violence in the course of
      their work, the overwhelming majority of threats and assaults against caregivers
      come from patients (Type II), justifying emphasis on this type of violence.
      Individual nurses and direct care providers have very little influence over the
      level of violence in their workplaces, but through collective action are poised
      to influence policies designed to protect the health care workforce.

PMID- 15482094
TI  - Pain assessment and management in aging.
AB  - Pain in the absence of disease is not a normal part of aging, yet it is
      experienced daily by a majority of older adults in the United States. Older
      adults are at high risk for undertreatment of pain due to a variety of barriers.
      These include lack of adequate education of health care professionals, cost
      concerns and other obstacles related to the health care system, and patient
      related barriers, such as reluctance to report pain or take analgesics.
      Unrelieved pain in the older adult has significant functional, cognitive,
      emotional, and societal consequences. Pain control begins with a thorough
      assessment, including an extensive history and physical examination. This
      information guides the plan of care, including both pharmacologic and
      nonpharmacologic therapies. Pharmacologic therapies include non-opioids, opioids,
      and adjuvant analgesics. Nonpharmacologic techniques include cognitive-behavioral
      strategies, such as distraction, guided imagery, education, and prayer, and
      physical measures, including heat, massage, bracing, and assistive devices.
      Health care professionals must be cognizant of the special pain-related needs of
      this fastest growing segment of the population.

PMID- 15482095
TI  - Receptiveness, use and acceptance of telehealth by caregivers of stroke patients
      in the home.
AB  - This descriptive study identified factors that influenced the receptiveness, use
      and acceptance of telehealth videophones by 21 family caregivers of stroke
      patients in the home setting. Potential obstacles to the receptiveness towards
      videophones included concerns by the caregiver about maintaining home security,
      limited need for health care support, very low or high degree of burden in
      caregiving, and discomfort or disinterest in using technology. Identification of
      possible impediments to the use of videophones is vital prior to developing and
      evaluating programs using telehealth as a method of rehabilitative technology.

PMID- 15482096
TI  - State involvement in professional nursing development in Israel: promotive or
      restrictive.
AB  - This article describes the role of the Israeli Ministry of Health's Nursing
      Division in regulating the development of the nursing profession and the nursing
      care provided. First, factors influencing professional nursing in Israel and the
      development of the Ministry of Health's Nursing Division are presented. Then,
      examples of the Nursing Division's influence on nursing practice, the process of
      statutory authorization used to facilitate this influence, and future Nursing
      Division initiatives are discussed. The article concludes by noting that, on
      balance, ministerial (governmental) involvement strengthens the nursing
      profession and the quality of nursing care provided, yet may also restrict
      nurses' private concerns.

PMID- 15482097
TI  - The current state of antibacterial research.

PMID- 15482099
TI  - Clarithromycin (Biaxin) extended-release tablet: a therapeutic review.
AB  - Clarithromycin (Biaxin) extended-release tablets, an advanced generation
      macrolide, were recently introduced into the USA for the treatment of acute
      exacerbations of chronic bronchitis, community-acquired pneumonia and acute
      maxillary sinusitis. The reformulation is intended to improve both patient
      compliance and tolerability. The extended-release tablets allow convenient once
      daily dosing (1000 mg). The extended-release formulation has been shown to be
      equivalent to the immediate-release formulation concerning area under the plasma
      concentration time curve. In comparative clinical trials for acute exacerbations
      of chronic bronchitis, community-acquired pneumonia and acute maxillary
      sinusitis, clarithromycin extended-release tablets were equivalent to the
      immediate-release formulation concerning clinical efficacy and bacterial
      eradication, with improved gastrointestinal tolerability. Similar efficacy and
      gastrointestinal tolerability results were demonstrated in a recent comparative
      study of clarithromycin extended-release formulation and amoxicillin-clavulanate
      in patients with acute exacerbations of chronic bronchitis. Clarithromycin
      extended-release 1000 mg daily has also been shown to be equivalent to
      levofloxacin 500 mg daily for the treatment of community-acquired pneumonia in a
      recent study. The macrolide class of antimicrobials, including clarithromycin
      extended-release, continues to be a safe and efficacious choice for the out
      patient management of community-acquired bacterial respiratory tract infections.

PMID- 15482100
TI  - Potential of acyclic nucleoside phosphonates in the treatment of DNA virus and
      retrovirus infections.
AB  - The acyclic nucleoside phosphonates [HPMPC: cidofovir, Vistide; PMEA: adefovir
      dipivoxil, Hepsera; and PMPA: tenofovir, Viread] have proven to be effective in
      vitro (cell culture systems) and in vivo (animal models and clinical studies)
      against a wide variety of DNA virus and retrovirus infections, for example,
      cidofovir against herpesvirus [herpes simplex virus type 1 and 2, varicella
      zoster virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus type 6, 7
      and 8), polyoma-, papilloma-, adeno- and poxvirus (variola virus, cowpox virus,
      vaccinia virus, molluscum contagiosum virus and orf) infections; adefovir against
      herpesvirus, hepadnavirus [human hepatitis B virus] and retrovirus [HIV type-1
      and 2, simian immunodeficiency virus and feline immunodeficiency virus]
      infections; and tenofovir against both hepadna- and retrovirus infections.
      Cidofovir has been officially approved for the treatment of cytomegalovirus
      retinitis in AIDS patients, tenofovir disoproxil fumarate (Viread) for the
      treatment of HIV infections (i.e., AIDS) and adefovir dipivoxil for the treatment
      of chronic hepatitis B.

PMID- 15482101
TI  - Antibiotic resistance in Staphylococcus aureus: concerns, causes and cures.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is currently a predominant and
      dangerous nosocomial pathogen. Unfortunately, infections caused by this organism
      are becoming more difficult to treat as further evolution of drug resistance
      occurs within the pathogen. Vancomycin has become the drug of choice for treating
      MRSA infections. However, treatment failures, adverse side effects and the
      emergence of vancomycin-resistant MRSA are leading to urgent requirements for
      alternative antiMRSA therapies. Linezolid is a new agent recently developed for
      Gram-positive infections, including MRSA. However, resistance to this drug is
      already developing. The need for superior antiMRSA drugs is therefore highly
      evident. This article explores some of the opportunities for the development of
      new treatments for MRSA. These arise principally from extensions of existing drug
      classes and the discovery of novel agents by genome-driven technologies. Other
      possibilities concern the re-evaluation of earlier pharmacophores that have not
      so far been developed as antiMRSA agents.

PMID- 15482102
TI  - Combating infections in hematopoietic stem cell transplant recipients.
AB  - Infections with a diverse group of microorganisms remain the leading causes of
      morbidity and mortality after hematopoietic stem cell transplantation.
      Importantly, the epidemiology of infectious complications has shifted
      substantially with changes in antimicrobial prophylaxis, conditioning regimens
      and graft manipulation, such that invasive mould infections and late viral
      infections are now the over-riding concerns. New antivirals and antifungals have
      entered clinical practice and hold considerable promise for improved outcomes.

PMID- 15482103
TI  - Optimized antiretroviral therapy: the role of therapeutic drug monitoring and
      pharmacogenomics.
AB  - The identification of relationships between plasma concentrations of protease
      inhibitors and later, the non-nucleoside reverse transcriptase inhibitors and
      their efficacy and toxicity has caused a growing interest in the concept of
      therapeutic drug monitoring in the treatment of HIV infection. Some evidence
      suggests a beneficial effect of therapeutic drug monitoring of protease
      inhibitors. More recently, plasma protease inhibitor concentrations have been
      combined with viral susceptibility into one parameter, the inhibitory quotient,
      which may be a better predictor of the response to therapy, especially in
      pretreated patients. This paper reviews the current literature on therapeutic
      drug monitoring and the inhibitory quotient in the management of HIV infection
      and speculates on the future role of pharmacogenomics in this therapeutic area.

PMID- 15482104
TI  - Cytokine therapies in HIV-1 infection: present and future.
AB  - Since the introduction of highly active antiretroviral therapy (HAART), HIV
      related deaths have declined dramatically in the developed world. However, HAART
      is neither able to eradicate the virus nor are its immunomodulatory effects
      sufficient to effect complete control of the virus. In addition, the long-term
      use of HAART is complicated by drug-related toxicities and compliance issues,
      both of which impact upon the development of viral resistance. The failure of
      structured treatment interruption strategies in those with chronic HIV-infection
      combined with the above limitations, has prompted renewed interest in
      immunotherapy. Cytokines and therapeutic vaccination have been proposed as HAART
      adjunctive and HAART-sparing treatments in HIV-infection, and the current and
      future role of cytokine therapy in this disease will be the subject of this
      review.

PMID- 15482105
TI  - The next generation of HIV/AIDS drugs: novel and developmental antiHIV drugs and
      targets.
AB  - There are presently 42 million people worldwide living with HIV/AIDS, the
      majority of which have limited access to antiretrovirals. Even if worldwide
      penetration was possible, our current chemotherapeutic strategies still suffer
      from issues of cost, patient compliance, deleterious acute and chronic side
      effects, emerging single and multidrug resistance, and generalized treatment and
      economic issues. Even our best antiretroviral therapeutic strategy, highly active
      antiretroviral therapy (HAART), falls short of completely suppressing HIV
      replication. Therefore, expansion of current therapeutic options by discovering
      new antiretrovirals and targets will be critical in the coming years. This review
      addresses the current status of reverse transcriptase and protease inhibitor
      development, and summarizes the progress in emerging classes of HIV inhibitors,
      including entry (T-20, T-1249), coreceptor (SCH-C, SCH-D), integrase (beta
      Diketos) and p7 nucleocapsid Zn finger inhibitors (thioesters and PATEs). In
      addition, the processes of virus entry, PIC transport to the nucleus, HIV
      interaction with nuclear pores, Tat function, Rev function and virus budding
      (Tsg101 and ubiquitination) are examined, and proof of concept inhibitors and
      potential antiviral targets discussed.

PMID- 15482106
TI  - Structured treatment interruptions in HIV infection: benefit or disappointment?
AB  - Many investigators are and have been studying the impact of structured treatment
      interruptions in HIV patients on subsequent viral control, HIV-specific cellular
      and humoral immunity, improvement of quality of life, and reduction of side
      effects and costs. Although varying treatment schedules have been followed and
      few clinical trials of different cohort size have been completed, tentative
      conclusions can already be drawn. Firstly after the initiation of treatment
      during acute infection followed by structured treatment interruptions, some
      patients maintained low level viremia during many months, such control of viremia
      has not been observed after the initiation of treatment during chronic infection
      followed by structured treatment interruptions. Second, structured treatment
      interruptions lead to an increase in frequencies of HIV-specific CD8(+) T-cell
      populations, however, these frequencies are not above pretreatment frequencies in
      chronically infected patients. Third, HIV-specific CD4(+) T-cell responses can be
      induced or enhanced during structured treatment interruptions but this
      augmentation was usually only transient. Finally, selection of drug-resistant
      virus variants may occur during structured treatment interruptions but clinical
      resistance to treatment has been quite rare. The initial hopes that structured
      treatment interruptions would substantially enhance immune control in the absence
      of therapy have not been confirmed, particularly in patients who initiated
      therapy during chronic infection. Additional immune-stimulatory interventions are
      now being considered and tested, such as administration of cytokines or
      vaccination. Furthermore, the demonstration of reduced side effects or costs due
      to structured treatment interruptions awaits the completion of large, comparative
      studies with a follow-up of several years.

PMID- 15482107
TI  - Early bactericidal activity of antituberculosis agents.
AB  - The early bactericidal activity (EBA) of an antituberculosis agent is arbitrarily
      defined as the fall in log(10) colony forming units (cfu) of Mycobacterium
      tuberculosis per ml sputum per day during the first 2 days of treatment.
      Determining the EBA is an important preliminary step in the clinical evaluation
      of an antituberculosis agent. We review the results of eight published studies of
      the EBA of different antituberculosis agents, the impact of these results on our
      understanding of the actions of the respective agents, the clinical
      characteristics and sputum findings of patients included in these studies, and
      explore sources of variation in the EBA results. Patients in these studies had a
      mean age of 31-36 years, a mean weight of 50-57 kg, 67% were male and 56% had
      lung involvement covering an area of more than one lung, and 90% had
      multicavitary disease. None of these findings were related to EBA in any study.
      The mean log(10) cfu per ml sputum in the first specimen was 6.474. This was
      related to radiological extent of disease and cavity size in one study (p <
      0.001) and, in the case of isoniazid to EBA with a rise in EBA of 0.094 (95% CL
      0.029-0.158) for each tenfold rise in cfu counts/ml sputum. The overall variation
      in EBA in these studies was 0.0303, that due to laboratory processing of
      specimens was 0.0011, and due to patient characteristics and sputum sampling
      0.0212. The EBA is a reproducible investigation that has contributed
      significantly to our knowledge of the actions and characteristics of both
      established and new antituberculosis agents. The greatest source of variation in
      EBA results appears to be that due to interpatient variation in disease
      characteristics and sputum sampling.

PMID- 15482108
TI  - A plethora of targets, a paucity of drugs: progress towards the development of
      novel chemotherapies for human African trypanosomiasis.
AB  - Human African trypanosomiasis is a major health problem in large regions of
      Africa. Current chemotherapeutic options are limited and far from ideal. A
      diverse range of drug targets has been identified and validated in trypanosomes.
      These include several organelles (glycosomes, acidocalcisomes, kinetoplast) that
      are not represented in the mammalian host and biochemical pathways that differ
      significantly from host counterparts (carbohydrate metabolism, protein and lipid
      modification, response to oxidative stress, cell cycle). However, there has been
      little progress in developing novel drugs. Pharmaceutical companies are unwilling
      to invest in the development of drugs for a market that comprises some of the
      worlds poorest people. This review highlights some of the most attractive drug
      targets in trypanosomes.

PMID- 15482109
TI  - The art of serendipity: killing of Caenorhabditis elegans by human pathogens as a
      model of bacterial and fungal pathogenesis.
AB  - The nematode worm, Caenorhabditis elegans, has been used to develop a facile
      model system of host-pathogen interactions to identify basic evolutionarily
      conserved pathways associated with microbial pathogenesis. The model involves the
      killing of Caenorhabditis elegans by a variety of human pathogens. Several
      virulence-related genes in a variety of pathogens previously shown to be involved
      in mammalian infection have also been shown to play a role in Caenorhabditis
      elegans killing. Screening of large numbers of microbial mutants for attenuation
      in a mammalian model would require thousands of mice, rats or rabbits. In
      contrast, the Caenorhabditis elegans model allows rapid identification of mutants
      in microbial genes associated with pathogenesis and then these phenotypes can be
      confirmed in a relevant mammalian model.

PMID- 15482110
TI  - Sulfadiazine and pyrimethamine in the postnatal treatment of congenital
      toxoplasmosis: what are the options?
AB  - Pre- and neonatal screening for congenital toxoplasmosis rests upon the
      assumption that treatment is beneficial on either acute symptoms or in preventing
      later reactivation. Postpartum treatment of congenital toxoplasmosis with
      sulfadiazine and pyrimethamine has remained almost unchanged for 50 years. More
      recently, sulfadiazine has been substituted by sulfadoxine, which has a much
      longer half-life and provides a basis for a dose schedule with higher compliance.
      Newer drugs with potential effects against Toxoplasma gondii, such as
      azithromycin, atovaquone and clindamycin, require further evaluation in animal
      models and human studies. No randomized controlled trials have ever been
      conducted. The available studies are either observational studies of groups of
      referred patients or observational studies with historical controls accrued over
      many years, often decades. Pre- and neonatal screening for congenital
      toxoplasmosis is performed on more than two million pregnant women every year in
      Europe, North and South America at the estimated cost of more than 500 million
      annually. The benefit needs to be documented by a prospective, placebo-controlled
      randomized study, which needs to be organized and financed by the countries
      performing nationwide, universal screening programs.

PMID- 15482111
TI  - Ureaplasma urealyticum airway colonization and pulmonary outcome in neonates.
AB  - Ureaplasma urealyticum genital tract colonization of pregnant women has been
      associated with an adverse pregnancy outcome, while its consequent perinatal
      transmission has been implicated in the development of respiratory disease of the
      neonate. Clinical manifestations or contributions of ureaplasmal airway
      colonization in newborns mainly include pneumonia, precocious dysplastic changes
      and chronic lung disease; although systemic disease has also been documented.
      This review aims to summarize current diagnostic techniques, pathogenetic
      mechanisms and pathological data in an attempt to establish an optimal
      therapeutic approach regarding neonatal U. urealyticum respiratory infection.
      Related morbidity and mortality, along with the high economic impact of neonatal
      respiratory disease worldwide, renders this topic particularly interesting and
      promotes further research in this field.

PMID- 15482112
TI  - Controversies and uncertainties in managing SARS.

PMID- 15482113
TI  - Superinfections create further HIV vaccine complications.

PMID- 15482114
TI  - Treatment of Acanthamoeba keratitis.
AB  - The treatment of Acanthamoeba keratitis has now been possible since the first
      successful therapy developed in the mid 1980s with a combination of propamidine
      0.1% (Brolene) and neomycin 1%. However, only half the patients responded to this
      regimen as the cysts were often resistant to neomycin and relatively insensitive
      to propamidine. This led to research for better therapy, culminating in the mid
      1990s with research in Glasgow demonstrating much increased effectiveness with
      use of the biguanide chlorhexidine 0.02% and in London and Bristol for similar
      effectiveness with the polymeric polyhexamethylene biguanide (PHMB) 0.02%. Both
      biguanides were combined with propamidine for enhanced effectiveness but were
      also shown to be effective as monotherapy. While this therapy inactivates the
      trophozoites and cysts in Acanthamoeba keratitis in the majority of patients
      (approximately 90%), there have been notable failures particularly when
      presentation is late with deep stromal infection. Additional highly
      acanthamoebicidal drugs are needed that can penetrate the stroma for synergistic
      action. This role may be taken up by certain antineoplastic drugs, such as
      alkylphosphocholine-1 (Miltefosine), that also have antiprotozoal activity.

PMID- 15482115
TI  - The effect of antibiotic treatment on active trachoma and ocular Chlamydia
      trachomatis infection.
AB  - Antibiotics are one of four arms of the SAFE strategy for the control of
      trachoma, an eye infection that is responsible for more cases of blindness than
      any condition other than cataract. The evidence for the use of topical
      tetracycline and oral tetracycline, doxycycline, erythromycin, cotrimoxazole and
      azithromycin in trachoma are reviewed here and a number of issues are nominated
      as research and policy priorities.

PMID- 15482116
TI  - Emerging aspects of Buruli ulcer.
AB  - Buruli ulcer, caused by the pathogen Mycobacterium ulcerans, is a major
      mycobacteriosis that affects people in scattered foci in the third world. It is
      amongst the most neglected of diseases in terms of primary healthcare strategies.
      However, this is changing as the World Health Organization launches a number of
      major global initiatives. Recent progress includes the unraveling of the genetic
      structure of the pathogen, examination of the mechanisms of virulence and the
      role of chemotherapy in disease treatment and prevention of recurrence, together
      with strategies aimed at reducing the economic burdens placed upon healthcare
      budgets of poorer nations. This review focuses upon the recent developments and
      the understanding of the disease, with particular focus on potential
      chemotherapy.

PMID- 15482117
TI  - Rhinovirus infections and adenoidal hypertrophy: do they interact with atopy in
      children?
AB  - Modern diagnostic methods allow the evaluation of the connection between
      rhinoviruses and atopy. Recent studies suggest that rhinoviruses are present in
      the adenoids at higher titers than in other specific sites, after inoculation of
      nasal mucosa or conjunctiva in volunteers. Therefore, it is possible that they
      might be responsible for specific local changes, while such changes may be
      influenced by atopy. This review focuses on the interactions between rhinoviral
      infection, the host's immune status and adenoidal disease.

PMID- 15482118
TI  - Pneumolysin in the immunopathogenesis and treatment of pneumococcal disease.
AB  - Recent insights into the immunopathogenesis of pneumococcal infection, a common
      and significant cause of morbidity and mortality, have implicated pneumolysin as
      being a prominent virulence factor, which may play a role in microbial
      colonization, invasion and dissemination, as well as tissue inflammation. Being a
      highly immunogenic polypeptide produced by all clinically relevant pneumococcal
      isolates, pneumolysin is recognized as a potential carrier protein for
      polysaccharide conjugate vaccines, while in the setting of acute disease,
      promising pneumolysin-directed pharmacological strategies include, among others,
      macrolides and corticosteroids.

PMID- 15482120
TI  - Antibiotic resistance in the intensive care unit setting.
AB  - Antibiotic resistance is an important factor influencing clinical outcome for
      patients in intensive care units. It is also associated with increased healthcare
      costs resulting from prolonged patient stays. The problem of antibiotic
      resistance is particularly acute in intensive care units because they house
      seriously ill patients who are predisposed to infection, as a result of which,
      antibiotic use is extremely common. Strategies for controlling resistance in
      intensive care units have focused on attempting to reduce unnecessary antibiotic
      use, while at the same time ensuring adequate antibiotic cover is provided. The
      formulation of policies for the effective use of antibiotics in individual
      intensive care units requires a multidisciplinary approach, entailing regular
      epidemiological surveillance, together with input from critical care specialists,
      infectious disease specialists and pharmacists.

PMID- 15482119
TI  - Antimicrobial resistance: cost and containment.
AB  - There is growing evidence that antimicrobial resistance causes serious
      consequences for individuals as well as leading to increased healthcare costs.
      The containment of resistance is therefore a policy problem which will impact on
      all health systems in the next few years. Unfortunately, there is, as yet, no
      definitive evidence suggesting that particular control measures are successful in
      containing either the emergence or transmission of antimicrobial resistance.
      Furthermore, few studies contain information about costs and even where there is
      such information it is generally inadequate because of the narrow perspectives
      from which analyses are conducted. In part, this is due to methodological
      problems associated with the inclusion of cost data: measuring and valuing what
      are often intangible costs; identifying costs associated with organizational
      change; and accounting for interaction between costs at levels from the
      individual to the international. Good quality research, including both economic
      evaluation and comprehensive economic modelling, is required to determine the
      most cost-effective combination of strategies to pursue in combating resistance,
      and to find ways around these methodological difficulties.

PMID- 15482121
TI  - Recent developments in the prevention of surgical site infections: preoperative
      screening and postoperative surveillance.
AB  - The purpose of this review is to cover the literature on the prevention of
      postsurgical infections in the period January 2002 to May 2003. Only articles
      that address novel insights in the prevention of infections are included in this
      review. The most interesting findings were observed in preoperative screening of
      patients for nasal carriage of Staphylococcus aureus. Eradication of
      Staphylococcus aureus in nasal carriers resulted in reduction of postsurgical
      nosocomial infections due to (endogenous) S. aureus infections. Furthermore,
      postoperative surveillance studies revealed insight in the incidence of surgical
      site infections, showed the use of risk indices and identified risk factors
      important for the development of postsurgical infections.

PMID- 15482122
TI  - Towards the prevention of transfusion-transmitted infectious diseases.
AB  - Transfusion-transmission of viral infections, such as HIV and hepatitis C virus,
      were once the scourge of blood transfusion. However, due to remarkable progress
      over the last 30 years, tests for viral proteins, antibody responses and more
      recently, viral nucleic acids, have virtually eliminated these risks. This review
      summarizes these advances in an historical context, describes new methodologies
      on the horizon, and discusses residual infectious risks associated with blood
      transfusion.

PMID- 15482123
TI  - Antimicrobial treatment of prostatitis.
AB  - The aim of this review is to emphasize the role of antimicrobial treatment in
      prostatitis. Especially in chronic bacterial prostatitis, the selection of an
      appropriate antimicrobial agent with optimal pharmacokinetics for prostatic
      secretion and tissue is important. The theoretical background of drug penetration
      into the prostate is outlined, emphasizing the phenomenon of ion-trapping and the
      role of nonionic diffusion of weak acids, bases and amphoteric drugs across
      biological membranes with a pH gradient. Determination of drug concentrations in
      human prostatic secretion are problematic because of possible urinary
      contamination. Studies have been carried out mainly in healthy volunteers. The
      results have to be interpreted with caution, if not care was taken to rule out or
      at least identify urinary contamination. Analyzing the concentrations of various
      fluoroquinolones in prostatic and seminal fluid as well as in prostatic tissue,
      it becomes obvious that the fluoroquinolones differ not only in plasma
      concentrations but also in their penetration ability to these sites. In spite of
      intensive investigations, our knowledge is still limited concerning the
      mechanisms that govern the transport of antibiotic drugs into and their activity
      in the various prostatic compartments and how the findings can be applied
      clinically. Nevertheless, overall the concentrations at the site of infection of
      most of the fluoroquinolones with this indication should be sufficient for the
      treatment of chronic bacterial prostatitis and vesiculitis caused by susceptible
      pathogens.

PMID- 15482124
TI  - Review of antiviral therapy for herpes labialis, genital herpes and herpes
      zoster.
AB  - Acyclovir (Zovirax) was approved for the treatment of herpesvirus infections
      almost two decades ago. It was the first agent in a novel group of antiviral
      medications that now include valacyclovir (Valtrex), penciclovir (Denavir and
      famciclovir (Famvir). These agents have made a dramatic impact on the morbidity
      associated with herpes simplex virus infections and herpes zoster. Topical and
      oral antiviral use have shown modest but statistically significant efficacy in
      treating herpes labialis with most studies demonstrating a significant reduction
      in episode length and/or healing time. Oral acyclovir, valacyclovir and
      famciclovir are efficacious and safe for the treatment of the first episode and
      recurrent genital herpes and are useful as suppressive therapy for individuals
      with frequent genital herpes recurrences. In addition, high doses of oral
      acyclovir, valacyclovir and famciclovir have been shown to speed the healing of
      herpes zoster, and data suggests that these agents also decrease associated acute
      and chronic pain in people of 50 years of age or older. Further research is
      required to clarify the safety of these agents in pregnant women with genital
      herpes, the role of antiviral therapy in decreasing the sexual transmission of
      genital herpes, and the efficacy and cost-effectiveness of these agents in
      treating herpes zoster in people below the age of 50 years.

PMID- 15482125
TI  - A review of chemotherapeutic approaches to the treatment of cryptosporidiosis.
AB  - This review focuses on chemotherapies used against the parasite, Cryptosporidium
      parvum, the causative agent of cryptosporidiosis. Populations at risk from severe
      morbidity or mortality from cryptosporidiosis are discussed with particular
      reference to those infected with HIV. The review then examines chemotherapies
      used in the clinical setting, as well as a number of in vitro and in vivo
      experimental studies. It begins with a discussion of the targets within
      Cryptosporidium that have been the foci of past treatments and then examines
      novel target sites that may present an exploitable alternative. Some of the novel
      target sites discussed include the recently discovered apicomplexan plastid and
      its associated pathways. Lastly, the review examines tubulin as a potential
      anticryptosporidial target in view of the fact that it has been exploited
      successfully for almost 50 years for the treatment of helminthiasis. The review
      concludes with a five-year outlook on the future of anticryptosporidial drug
      design.

PMID- 15482126
TI  - Prophylaxis and treatment of hepatitis B recurrence after liver transplantation
      in the antiviral era.
AB  - Redistribution of virions from extrahepatic reservoirs with resultant reinfection
      of the graft is a serious complication after liver transplantation for hepatitis
      B-related liver disease. Prophylaxis of hepatitis B virus recurrence is a major
      issue in these patients. With the introduction of passive immunoprophylaxis and
      the development of antiviral drugs, liver transplantation has evolved as an
      established therapy of hepatitis B-induced end-stage liver failure. However, even
      under indefinite monoprophylaxis, a significant percentage of patients develop
      reinfection due to a high mutation rate of the hepatitis B virus. Progress,
      especially in the field of antiviral therapy, has opened new strategies,
      including combination prophylaxis and therapy, which further improve outcome. On
      the other hand, the broad use of antiviral drugs brings about new problems such
      as resistance formation prior to liver transplantation. In addition, due to the
      high costs of hepatitis B immunoglobulin alternatives such as prophylaxis with
      nucleoside analogs or vaccination are increasingly being investigated.

PMID- 15482127
TI  - Natural products and synthetic compounds as immunomodulators.
AB  - Research on immunomodulation by natural products or synthetic derivatives is of
      key interest for anti-infective therapy for a number of reasons. Many plant
      remedies well-known in traditional medicine or refined natural products in
      clinical use exert their anti-infective effects not only (if at all) by directly
      affecting the pathogen. At least part of their effect is indirect, by stimulating
      natural and adaptive defense mechanisms of the host. These findings have now
      given many empirical therapies a rationale, scientific basis and thereby a means
      for 'intelligent' improvement. In discovering the molecular mechanisms by which
      known remedies exert their effects, chosen elements further down the 'chain of
      command' might be synthesized and applied directly for more rapid and selective
      cure, omitting unwanted side effects. The direct use of recombinant cytokines,
      often in combination with antibiotics, is one consequence of this rationale.

PMID- 15482128
TI  - A designer drug against influenza: the NA inhibitor oseltamivir (Tamiflu).
AB  - The description of the first two designer antiviral drugs to fight influenza was
      a ground breaking advance. Targeted against the influenza neuraminidase enzyme
      these inhibitors have been shown to reduce both the severity and duration of
      influenza illness. Importantly, it is expected that these neuraminidase
      inhibitors would be effective against influenza pandemic strain and could
      therefore be vital at reducing the potentially devastating consequences of such
      an outbreak. Despite the demonstrated efficacy of these drugs, they are not
      commonly used, particularly in the UK, and there is substantial concern that in
      the event of a pandemic or even a severe epidemic there could be substantial
      morbidity and mortality. SARS has shown that the public and media response to a
      serious epidemic is not always rational and this could easily become panic if it
      became apparent that treatment was possible, but not available.

PMID- 15482129
TI  - Inhibition of HIV by chemokine receptor antagonists: exciting new targets,
      complex development.

PMID- 15482133
TI  - Overlooked aspects concerning development and spread of antimicrobial resistance.
      Central European Symposium on Antimicrobial Resistance, Brijuni, Croatia, 4-7
      July, 2003.

PMID- 15482134
TI  - Moxifloxacin (Avelox): a novel fluoroquinolone with a broad spectrum of activity.
AB  - Moxifloxacin (Avelox) is a recently-developed fluoroquinolone that has a broad
      spectrum of antimicrobial activity, including typical respiratory pathogens,
      atypical and intracellular respiratory pathogens, Gram-negative pathogens and
      many anaerobes. This spectrum of activity makes moxifloxacin particularly
      suitable for the therapy of community-acquired respiratory tract infections. It
      also has enhanced activity against specific bacteria, such as Mycobacteria spp.
      and Legionella. Moxifloxacin has pharmacologic characteristics that support once
      daily dosing regimens and dual routes of excretion that require little or no
      adjustment for renal or hepatic insufficiency. The drug has maintained an
      excellent safety profile based upon broad global usage, and no adverse events
      have occurred that were unanticipated. Streptococcus pneumoniae, which are
      resistant to earlier fluoroquinolones, are less likely to be resistant to
      moxifloxacin.

PMID- 15482135
TI  - Levofloxacin: update and perspectives on one of the original 'respiratory
      quinolones'.
AB  - The fluoroquinolone class of antimicrobials has enjoyed enormous clinical and
      marketing success over the past 20 years. These drugs have proven to be extremely
      useful in a broad range of clinical indications including both common community
      acquired as well as nosocomial bacterial infections. Levofloxacin (Levaquin,
      Tavanic), like ciprofloxacin (Cipro), has established an enviable record of safe
      and efficacious use, and in many ways has become the agent against which all of
      the newer fluoroquinolones are judged. New clinical indications in complicated
      skin and skin structure infections, nosocomial pneumonia and chronic bacterial
      prostatitis continue to expand the important role of this already versatile drug.
      In addition, the use of 'short-course, high-dose' therapies are being studied in
      indications, such as community-acquired pneumonia, in an effort to optimize the
      efficacy and convenience of the drug while minimizing the future development of
      resistance. As the use of levofloxacin continues to expand, future challenges
      will include the threat of increasing antimicrobial resistance and the
      availability of newer alternative agents, both newer fluoroquinolones as well as
      agents of other antibiotic classes.

PMID- 15482136
TI  - The role of lopinavir/ritonavir (Kaletra) in the management of HIV infected
      adults.
AB  - As the HIV pandemic enters its third decade, more sophisticated and efficacious
      therapies are continually being developed. This article provides an in-depth
      review of the first coformulated boosted protease inhibitor available on the
      world market, lopinavir/ritonavir (Kaletra). Included in this review is an
      overview of the current market place, the chemistry, pharmacokinetics, clinical
      efficacy and side-effect profile of lopinavir/ritonavir. In addition, an expert
      opinion and commentary on the clinical applications of this drug is provided.

PMID- 15482137
TI  - Atazanavir: improving the HIV protease inhibitor class.
AB  - Protease inhibitors are potent agents against HIV but their use is constrained by
      poor pharmacokinetics, cross-resistance and metabolic toxicities. Atazanavir
      [Reyataz] is a new protease inhibitors with once-daily dosing and minimal lipid
      and glycemic effects. Resistance studies of clinical isolates reveal a mutational
      pattern distinctive from that of other protease inhibitors. Atazanavir selects
      for the I50L mutation in HIV protease that confers increased susceptibility to
      other protease inhibitors in vitro. Clinical trials have shown comparable
      efficacy to nelfinavir (Viracept) and efavirenz (Sustiva) in treatment-naive
      patients, and in preliminary studies, ritonavir-boosted atazanavir is effective
      in patients failing previous protease inhibitor-containing regimens. Reversible
      elevations in bilirubin occur in some patients but are not associated with
      hepatic injury. Atazanavir improves upon aspects of currently-available protease
      inhibitors and appears useful for initial and possibly subsequent HIV therapy.

PMID- 15482138
TI  - Tenofovir disoproxil fumarate (Viread) for the treatment of HIV infection.
AB  - Tenofovir disoproxil fumarate (Viread) is the first nucleotide analog reverse
      transcriptase inhibitor to be approved by the Food and Drug Administration for
      the treatment of HIV infection. It is a potent agent with a long intracellular
      half-life that allows for once-daily dosing. It has been well-tolerated in
      clinical trials to date, without evidence of long term toxicity, including the
      mitochondrial toxicity that has been associated with some nucleoside analog
      reverse transcriptase inhibitors. Since its approval in October 2001, tenofovir
      disoproxil fumarate has quickly become a widely used component of antiretroviral
      regimens for both treatment-naive and -experienced patients.

PMID- 15482139
TI  - Peginterferon-alpha 2a (40 kDa)/ribavirin combination for the treatment of
      chronic hepatitis C infection.
AB  - Chronic hepatitis C is the leading cause of liver disease and liver-related
      mortality in the western world. Treatment of this chronic viral infection has
      considerably improved with the introduction of ribavirin-interferon combination
      therapy. Ribavirin (Copegus, Rebetol) is a synthetic nucleoside analogue with
      broad antiviral effects. It is absorbed readily upon oral administration with
      meals. Daily doses of up to 1200 mg are usually well-tolerated, causing dose
      dependent haemolysis, reversible with dose reduction in most patients, in
      particular in those with renal insufficiency. In the circulation it is bound to
      erythrocytes, and eliminated by phosphorylation and deribolysation. The drug
      accumulates in blood with renal insufficiency. Impairment of hepatic function
      does not influence drug levels in the circulation. In animal studies, teratogenic
      and reproductive toxicity was shown. In chronic hepatitis C virus infection,
      monotherapy with ribavirin has no effect on concentrations of viral RNA or liver
      histology. Combination therapy with pegylated interferon-alpha2a (40 kDa)
      (Pegasys) produces significantly higher sustained virological response rates in
      infections with all viral genotypes, even in advanced stages of liver disease
      compared pegylated interferon-alpha2a monotherapy, adverse effects and quality of
      life are not significantly different.

PMID- 15482140
TI  - Hepatitis C-HIV coinfection: current and future therapy.
AB  - Coinfection with hepatitis C in HIV-infected patients has been reported in 15-70%
      of patients depending on the mode of acquisition of both viruses. As recent
      advances in HIV-directed antiviral therapy have markedly delayed HIV progression
      and mortality, the incidence of complications arising from hepatitis C-associated
      liver disease in coinfected patients is increasing exponentially. The interaction
      of HIV and hepatitis C is complex. It is clear that HIV infection negatively
      affects the natural history of hepatitis C, while HIV-directed therapy may
      enhance immunologic response and exacerbate hepatocellular injury induced by
      hepatitis C via immune reconstitution. In this review, the pathobiology, inter
      relation of hepatitis C and HIV infection in coinfected patients as well as
      present and future treatment in this unique patient population are discussed.

PMID- 15482141
TI  - Current and emerging therapeutic approaches to hepatitis C infection.
AB  - Hepatitis C virus is a frequent disease infecting an estimated 3% of the worlds
      population. It represents a major health problem and must be combated by all
      means. The aim of this review is to discuss the current treatment methods,
      including interferon-alpha, either standard or pegylated, and ribavirin. Emerging
      treatments will also be discussed for this potentially curable disease.

PMID- 15482142
TI  - Management of protozoa-related diarrhea in HIV infection.
AB  - Protozoa infections are an important cause of chronic diarrhea in patients
      infected with HIV. The introduction of highly active antiretroviral treatment to
      the management of HIV in the mid 1990s has led to a dramatic reduction in the
      incidence of these opportunistic infections in Europe and America. In contrast,
      in the developing world where such treatments are not readily affordable,
      protozoa-related diarrhea remains a major cause of morbidity and mortality in HIV
      infected individuals. In this review, the optimum investigations required to
      diagnose these pathogens in HIV-related diarrhea, as well as current treatment
      options, will be discussed.

PMID- 15482143
TI  - Clinical aspects, diagnosis and treatment of trichinellosis.
AB  - Trichinellosis, the human disease induced by worms of the genus Trichinella, is
      caused by the consumption of raw or undercooked meat of various types of animals
      and has a worldwide prevalence of approximately eleven million. Since there are
      no pathognomonic signs or symptoms, clinical diagnosis is difficult and the only
      reliable diagnostic methods are serodiagnosis and muscle biopsy. Treatment
      consists of benzimidazoles and glucocorticosteroids, yet in order for these drugs
      to be effective, they must be administered before the end of the acute stage;
      thus early diagnosis is fundamental. To aid in the recognition and treatment of
      trichinellosis, an overall description of its clinical aspects, diagnosis and
      treatment has been prepared.

PMID- 15482144
TI  - A review of tuberculosis: reflections on the past, present and future of a global
      epidemic disease.
AB  - Tuberculosis remains the leading cause of death worldwide from a single
      infectious organism. Approximately 32% of the world's population is infected and
      an estimated two million people die annually from this treatable disease. Over
      the past 50 years, with medical treatment and standard public health practices,
      tuberculosis diminished in developed countries and resulted in a loss of interest
      and funding for research in improving diagnostic and treatment options. In
      developing countries, efforts including BCG vaccination have failed to control
      tuberculosis and the disease continues to spread as the world becomes more
      globalized. At the same time, multidrug resistant tuberculosis has emerged,
      challenging even the most advance treatment centers. Better diagnostic
      techniques, control measures and treatment options are desperately needed but
      advances require worldwide commitment to battle this age-old disease.

PMID- 15482145
TI  - Advances in the management of Chlamydia pneumoniae infections.
AB  - One of the major characteristics of Chlamydia spp. is its ability to cause
      prolonged, often subclinical infections. Chronic, persistent infection with
      Chlamydia pneumoniae has been implicated in the pathogenesis of several chronic
      diseases initially not thought to be infectious, including asthma, arthritis and
      atherosclerosis. C. pneumoniae is susceptible in vitro to a wide range of
      antimicrobial agents that target either protein or DNA synthesis, including
      macrolides, ketolides, tetracyclines, quinolones and rifamycins. Practically all
      treatment studies evaluating presented or published to date have used serology
      alone for diagnosis of C. pneumoniae infection, which only provides a clinical
      end point. The results of several treatment studies that did perform culture
      found that erythromycin, azithromycin (Zithromax, clarithromycin (Biaxin,
      levofloxacin (Levaquin and moxifloxacin (Avelox had a 70 to 90% efficacy in
      eradicating C. pneumoniae from the respiratory tract of children and adults with
      pneumonia. Persistence of the organism does not appear to be due to the
      development of antibiotic resistance. However, one cannot extrapolate from this
      experience to the treatment of chronic C. pneumoniae infection, especially
      cardiovascular disease. As there are no reliable serologic markers for chronic or
      persistent C. pneumoniae infection, it cannot be determined who is infected and
      who is not, which means that it cannot be assumed that any effect seen is due to
      successful treatment or eradication of C. pneumoniae.

PMID- 15482146
TI  - Management of respiratory infections in the elderly.
AB  - Respiratory infections are common at all ages but are particularly sinister among
      the elderly because of the fragility and chronic comorbidity associated with this
      age group. The three types of respiratory infection in the elderly are community
      acquired pneumonia, acute exacerbation of chronic obstructive pulmonary disease
      and nonpneumonic respiratory tract infection. The etiology of these three types
      of infection includes classic bacteria, atypical pathogens and respiratory
      viruses. The relative frequency of each of the etiological groups as the
      causative agent of the infection varies significantly among these types of
      infection, but in all three types a significant proportion of infections involves
      more than one pathogen. The causative agent of respiratory infection in the
      elderly cannot be determined on the basis of clinical manifestation or the
      results of routine imaging procedures or laboratory tests. Thus, initial
      antibiotic therapy in these patients should be empiric, based on accepted
      guidelines. In recent years, the antipneumococcal fluoroquinolones have gained in
      stature as one of the best options to treat these infections. Pneumococcal and
      influenza vaccinations can reduce morbidity and mortality from respiratory
      infections in the elderly, so it is important that all elderly individuals are
      vaccinated through a structured program in the framework of primary care. The
      economic impact of respiratory infections in the elderly is primarily associated
      with the requirement for hospitalization in many of the cases. Any action that
      can reduce hospitalization rates has important economic ramifications. In light
      of the difficulty in reaching an early etiologic diagnosis in respiratory
      infections, it is essential to invest in the development of a compact diagnostic
      kit for the early stages of the disease, which could change reality in this
      important area of medicine.

PMID- 15482147
TI  - No easy way to exterminate 'superbugs' at the dawn of the third millennium.

PMID- 15482148
TI  - AIDSVAX fails to prove efficacious in large-scale trial.

PMID- 15482150
TI  - Itraconazole (Sporanox) in superficial and systemic fungal infections.
AB  - Itraconazole (Sporanox) is a triazole antifungal agent with a broad activity
      spectrum and favorable pharmacokinetic and safety profiles. Numerous clinical
      trials have established the efficacy and safety of itraconazole in the treatment
      of superficial fungal infections. In this field, full exploitation of its
      pharmacokinetics in keratinized tissues has led to the development of
      intermittent (pulse) treatment regimens that allow similar efficacy with lower
      overall drug exposure as well as a reduction in treatment costs. The additional
      anti-inflammatory action of itraconazole also makes it suitable for application
      in difficult-to-treat inflammatory skin disorders, such as seborrheic dermatitis.
      Recently, a new oral liquid formulation and an intravenous formulation have been
      developed, extending the therapeutic application of itraconazole to systemic
      fungal infections. Due to its broad activity spectrum and excellent tolerability,
      itraconazole is a valuable addition to the antifungal armamentarium used for
      prophylactic and empiric treatment in immunocompromised hosts.

PMID- 15482151
TI  - Impact of supervised injection facilities on community HIV levels: a public
      health perspective.
AB  - The health and social consequences of intravenous drug use pose major challenges
      to cities across North America. Preventable drug-related harms including
      accidental overdose, serious bacterial infections, injuries of violence and more
      recently, the emergence of HIV and hepatitis C, have major impacts on community
      health. Among the various interventions designed to reduce the harms associated
      with injection drug use, the establishment of a supervised injection facility is
      perhaps the most controversial. This review will focus on the potential impact of
      supervised injection facilities on HIV transmission in conjunction with current
      HIV prevention initiatives. This will include a review of the health and social
      consequences associated with illicit drugs use, the limitations of drug
      enforcement, and the potential impact of supervised injection facilities on
      reducing the harms associated with injection drug use.

PMID- 15482152
TI  - Use of observational data in evaluating treatments: antiretroviral therapy and
      HIV.
AB  - Observational data are increasingly used in various therapeutic areas to evaluate
      the use, effectiveness and side effects of new treatments. Whilst randomized
      clinical trials remain the gold standard for evaluating the efficacy of new
      agents, they have a number of limitations for HIV, including the limited number
      of combinations that are compared and the costs of long-term follow-up.
      Observational data from seroconverter and clinical cohorts have been used to
      compare the short- and longer-term effectiveness of different therapy
      combinations and to evaluate the longer-term risks associated with antiretroviral
      therapy. Furthermore, they provide the opportunity to evaluate the relative
      success of more complex patterns of therapy, such as sequencing of different
      regimens over time. However, because of the nature of these data, a number of
      potential biases may arise which can influence interpretation.

PMID- 15482153
TI  - Cutaneous leishmaniasis: current and future management.
AB  - Leishmaniasis remains a major world health problem that continues to increase in
      incidence. This review considers epidemiology, clinical features, diagnosis and
      current treatment options. Recent developments in the treatment of simple
      cutaneous leishmaniasis are discussed followed by speculation about future
      therapies.

PMID- 15482154
TI  - Chemotherapy for lymphatic filariasis: progress but not perfection.
AB  - Currently, only three drugs are used to control and treat the mosquito-borne
      parasitic disease lymphatic filariasis: diethylcarbamazine, ivermectin (Mectizan)
      and albendazole (Zentel). All interrupt transmission by eliminating microfilaria,
      the parasite stage that is responsible for transmission between hosts, but do not
      reliably kill the adult worms that are responsible for much of the pathology seen
      in the disease. There is an urgent need to develop drugs that will reliably kill
      adult worms and several compounds are under-going in vitro and animal testing. An
      alternative strategy - that of targeting symbiont bacteria within the parasite -
      has also shown promising results.

PMID- 15482155
TI  - New approaches to rapidly control foot-and-mouth disease outbreaks.
AB  - Economically, foot-and-mouth disease is the most important viral-induced
      livestock disease worldwide. The disease is highly contagious and foot-and-mouth
      disease virus replicates and spreads extremely rapidly. Recent outbreaks in
      previously foot-and-mouth disease-free countries and the potential use of foot
      and-mouth disease virus by terrorist groups have demonstrated the vulnerability
      of countries and the need to develop control strategies that can rapidly inhibit
      or limit spread of the disease. The current vaccine, an inactivated whole-virus
      preparation, has a number of limitations for use in outbreaks in disease-free
      countries. This review discusses the potential of the antiviral agent, Type I
      interferon, to produce rapid protection and proposes a combination strategy of an
      antiviral agent and a foot-and-mouth disease vaccine to induce both immediate and
      long-lasting protective responses.

PMID- 15482156
TI  - Host response to Neisseria meningitidis lacking lipopolysaccharides.
AB  - Plasma levels of lipopolysaccharides are closely associated with disease
      manifestations and outcomes in meningococcal infections. The knockout mutant lpxA
      Neisseria meningitidis completely lacking lipopolysaccharides has made it
      possible to study the contribution of nonlipopolysaccharide molecules in the
      bacterial cell wall to the host's response. The lpxA-N. meningitidis requires 10-
      to 100-fold higher concentrations of bacteria to elicit the same level of pro
      inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta and -6) as
      the wild type parent strain. It activates human mononuclear peripheral blood
      cells through CD14 and Toll-like receptor-2 receptor complex whereas the wild
      type strain activates these cells through the CD14-Toll-like receptor-4-MD2
      pathway. Dendritic cells are hardly activated by the lpxA-N. meningitidis. It is
      as efficient as the wild type strain in activating complement. The lpxA-N.
      meningitidis expresses pili but does not adhere or invade mucosal cells normally.
      The defensin-mediated adhesion of lpxA-N. meningitidis to the respiratory
      epithelial cells is severely reduced as compared with the wild-type strain.

PMID- 15482157
TI  - Pathogenesis of Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome is a postinfectious disorder caused by an aberrant immune
      response to an infectious pathogen, resulting in an autoimmune disease. As with
      other autoimmune diseases of infectious nature, the intricate balance of the
      numerous factors involved in the immune response may determine the outcome of the
      interaction between the microbe and host. Recent studies focusing on the role of
      cytokines and its network of related mediators and receptors suggest that any
      imbalance may make a significant contribution to the outcome of the infectious
      disease process. Better understanding of the pathogenesis of Guillain-Barre
      syndrome may lead to the discovery of newer therapeutics and may also serve as a
      model for studying other autoimmune diseases.

PMID- 15482158
TI  - Pseudomonal infection in cystic fibrosis: the battle continues.
AB  - Pseudomonas aeruginosa lung infection is the major cause of morbidity and
      mortality in patients with cystic fibrosis. Infection usually begins in childhood
      and is responsible for respiratory failure and death in most patients with cystic
      fibrosis. The organism triggers an exuberant chronic inflammatory reaction which
      damages the airways and leads to progressive loss of lung function. Over the last
      decade significant advances have been made in the understanding of the
      pathophysiology of cystic fibrosis airways disease. These should assist the
      development of new and better therapies to treat this pathogen. This review
      provides an overview of pseudomonal infection in cystic fibrosis, including
      mechanisms by which the bacteria may colonize the cystic fibrosis airway,
      persistence of pseudomonal infection and the biofilm mode of growth. Available
      treatments and possible novel approaches to therapy will be discussed.

PMID- 15482159
TI  - Current and future therapeutic approaches to the common cold.
AB  - For decades, investigators have strived to elucidate the pathogenesis, and hence
      a treatment, for the common cold. Therapy has been tried with a variety of
      agents, ranging from anecdotal folk remedies, to well-designed medications.
      Measures primarily directed to relieve the symptoms of the common cold, rather
      than specific antimicrobial agents, are the current main stay of therapy.
      Millions of patients would benefit from an easy-to-perform diagnostic test and
      specific therapy that works quickly, shortening the duration of illness and
      preventing further spread of infection.

PMID- 15482160
TI  - Control of influenza virus infection by immunity to conserved viral features.
AB  - Influenza has circulated among humans for centuries and kills more people than
      many newly emerging diseases. The present methods for control of influenza are
      not adequate, especially for dealing with a pandemic. In the face of a rapidly
      spreading outbreak, a race to isolate the virus and prepare a vaccine would
      probably not succeed in time to avoid great losses. Thus, additional anti
      infection strategies are needed. Broad cross-protection against widely divergent
      influenza A subtypes is readily achieved in animals by several means of
      immunization. How does cross-protection work in animals, and can we apply what we
      have learned about it to induce broad cross-protection in humans?

PMID- 15482161
TI  - Current diagnosis and treatment of infective endocarditis.
AB  - The incidence of infective endocarditis continues to rise with a yearly incidence
      of around 15,000 to 20,000 new cases in the USA. As a result, rapid diagnosis,
      effective treatment and prompt recognition of complications are essential to
      desirable clinical outcomes. Recent guidelines such as the Duke criteria have
      incorporated echocardiography for diagnosis of infective endocarditis, making
      this diagnostic test mandatory for patients with suspected infective
      endocarditis. The diversity of pathogens that can cause infective endocarditis,
      some of which cannot be cultured easily, makes diagnosis even more difficult.
      Coagulase-negative staphylococci and viridans streptococci groups continue to be
      the major causative microorganisms of infective endocarditis. In the case of
      culture-negative endocarditis or infective endocarditis caused by fastidious
      microorganisms, the polymerase chain reaction and probe-based diagnostic methods
      are available to clinical reference laboratories.

PMID- 15482162
TI  - New therapeutic agents for resistant Gram-positive infections.
AB  - Gram-positive bacteria are an increasingly common cause of community acquired and
      nosocomial infections, and their resistance to antibiotics is increasing. The
      recent reports from several continents of methicillin-resistant Staphylococcus
      aureus with reduced glycopeptide-susceptibility is of grave concern. New agents
      are required to meet these threats and several classes of compounds are under
      development. This review focuses on agents that have been recently licensed or
      are presently in clinical development for the treatment of serious multidrug
      resistant staphylococcal, enterococcal and pneumococcal infections, including
      methicillin-resistant S. aureus and vancomycin-resistant enterococci.

PMID- 15482163
TI  - Bacterial biofilms: a diagnostic and therapeutic challenge.
AB  - Bacteria have traditionally been regarded as individual organisms growing in
      homogeneous planktonic populations. However, bacteria in natural environments
      usually form communities of surface-adherent organisms embedded in an
      extracellular matrix, called biofilms. Current antimicrobial strategies often
      fail to control bacteria in the biofilm mode of growth. Treatment failure is
      particularly frequent in association with intracorporeal or transcutaneous
      medical devices and compromised host immunity. The rising prevalence of these
      risk factors over the last decades has paralleled the increase in biofilm
      infections. This review discusses the shortcomings of current therapies against
      biofilms both in theory and with clinical examples. Biofilm characteristics are
      described with a focus on new diagnostic and therapeutic targets.

PMID- 15482164
TI  - And now for something completely simple.

PMID- 15482165
TI  - Genes affect risk of contracting SARS.

PMID- 15482166
TI  - Disease watch.

PMID- 15482167
TI  - Thymalfasin for the treatment of chronic hepatitis B.
AB  - Chronic hepatitis B virus infection is a serious problem because of its worldwide
      distribution and possible adverse chronic sequelae, such as cirrhosis and
      hepatocellular carcinoma. Chronic hepatitis B infection is a dynamic state of
      interactions between the virus, hepatocyte and host immune response. Interferon
      alpha and direct antiviral agents, such as lamivudine (Epivir, GlaxoSmithKline),
      are effective in the therapy of chronic HBV infection but the efficacy is far
      from satisfactory. Thymalfasin (thymosin alpha1; Talpha1, Zadaxintrade mark,
      SciClone Pharmaceuticals, Inc.) is a 28-amino acid polypeptide produced
      synthetically but originally isolated from thymosin fraction 5, a bovine thymus
      extract containing a number of immunologically active peptides. In vitro studies
      have shown that Talpha1 can influence T-cell production and maturation, stimulate
      production of Th1 cytokines such as interferon-gamma and interleukin-2, and
      activate natural killer cell-mediated cytotoxicity. Seven randomized controlled
      studies on Talpha1 monotherapy in patients with chronic hepatitis B showed that 6
      months treatment with Talpha1 (1.6 mg twice-weekly) resulted in a significantly
      higher sustained response rate than untreated controls. The benefits of Talpha1
      therapy is usually not immediately apparent during therapy. There is a trend for
      complete virological response to increase or accumulate gradually after the end
      of thymosin therapy. The results of Talpha1 and interferon combination therapy in
      two open-label trials were also promising. In terms of the mechanisms of action,
      a combination of Talpha1 and nucleoside or nucleotide analogs is a logical
      approach in the control of chronic HBV infection and a randomized control study
      is ongoing.

PMID- 15482168
TI  - Peginterferon-alpha(2b) and ribavirin.
AB  - Hepatitis C virus infection is among the leading causes of chronic liver disease
      in the USA and has a worldwide prevalence of approximately 300 million people.
      Chronic hepatitis C virus is the most common indication for liver transplantation
      in the USA. Due to the chronic nature of hepatitis C virus infection, these
      numbers are expected to grow fourfold in the next decade. Interferon-alpha(2b)
      monotherapy followed by combination therapy with ribavirin have been used to
      treat chronic hepatitis C virus with limited success. The development of
      pegylated interferon-alpha(2b), (Peg-intron, Schering-Plough) instituted the next
      chapter in hepatitis C virus therapy. The demonstration of its safety and
      efficacy led to a major trial studying coadministration with ribavirin for
      compensated chronic hepatitis C virus infection. Pegylated interferon combination
      therapy has improved efficacy over standard interferon combination therapy
      without an increase in adverse effects. This article reviews the data regarding
      pegylated interferon-alpha(2b) with ribavirin therapy. The pharmacokinetics and
      pharmacodynamics of combination therapy will be presented along with clinical
      trial data. The efficacy and ease of usage of Pegintron and ribavirin support its
      use for chronic hepatitis C virus infection.

PMID- 15482169
TI  - Valganciclovir for the prevention and treatment of cytomegalovirus disease in
      immunocompromised hosts.
AB  - Valganciclovir (Valcyte, Roche), a prodrug of the deoxyguanosine analog
      ganciclovir (Cytovene, Roche), is indicated for induction and maintenance
      treatment of cytomegalovirus retinitis in patients with AIDS and for prevention
      of cytomegalovirus disease in selected high-risk solid organ transplant
      recipients. After oral administration, valganciclovir is rapidly absorbed and
      converted to ganciclovir by intestinal and hepatic esterases. Valganciclovir is a
      highly recognized substrate of the intestinal peptide transporter PEPT1, which
      underlies the tenfold higher bioavailability of ganciclovir after valganciclovir
      compared to oral ganciclovir administration. At oral dose of 900 mg,
      valganciclovir provides a systemic ganciclovir exposure that is comparable to
      intravenous ganciclovir, at the standard dose of 5 mg/kg of body weight.
      Subsequent phosphorylation of ganciclovir, which occurs preferentially within
      cytomegalovirus-infected cells, results in the active metabolite, ganciclovir
      triphosphate, which is responsible for suppressing viral DNA synthesis by
      competitively inhibiting the incorporation of the natural substrate
      deoxyguanosine into viral DNA and thereby, terminating cytomegalovirus
      replication.

PMID- 15482170
TI  - Nitazoxanide: a new broad spectrum antiparasitic agent.
AB  - Nitazoxanide (Alinia, Romark Laboratories) was synthesized based on the structure
      of niclosamide. In vitro studies have demonstrated activity against a broad range
      of parasites as well as some bacteria. Three controlled trials demonstrated
      efficacy in cryptosporidiosis, however, the efficacy in advanced AIDS patients
      (CD4 cell counts = 50) at approved doses was limited. Trials have also
      demonstrated efficacy comparable to metronidazole (Flagyl, GD Searle and Co.) in
      giardiasis with fewer side effects. Nitazoxanide is also effective versus
      intestinal helminths and tapeworms as well as in chronic fascioliasis. Side
      effects in clinical trials have been similar to placebo. Nitazoxanide is the
      first agent proven to be effective in cryptosporidiosis. It has also proven
      efficacy in giardiasis. Nitazoxanide is efficacious again intestinal helminths.
      Additional indications may be developed in the future.

PMID- 15482171
TI  - A review of linezolid: the first oxazolidinone antibiotic.
AB  - Resistance of Gram-positive bacterial pathogens, such as Staphylococcus aureus
      and Enterococcus faecium, to existing antibiotics continues to increase, and new
      antibiotics with activity against these pathogens are in demand. Linezolid
      (Zyvox, Pharmacia and Upjohn) is the first agent of a new class of antibiotics
      called the oxazolidinones. Linezolid possesses excellent microbial activity
      against a wide variety of Gram-positive pathogens including those resistant to
      methicillin and vancomycin (Vancocin, Eli Lilly). Linezolid is available for
      intravenous and oral administration and possesses excellent bioavailability. It
      exhibits good penetration into pulmonary, as well as skin and related structure
      tissues, and does not require dosage adjustment in hepatic or renal dysfunction.
      Linezolid is generally well-tolerated, with the predominant adverse effect
      manifesting as a duration dependent, reversible thrombocytopenia. Linezolid
      possesses monoamine oxidase inhibitor activity and caution is warranted with
      coadministration of adrenergic or seritonergic medications. Clinical trials
      conducted with linezolid in skin and structure infections, lower respiratory
      tract infections and vancomycin-resistant enterococcal infections demonstrate
      that linezolid is an effective therapy. Recent data suggest that linezolid may be
      superior to vancomycin for the treatment of infections caused by methicillin
      resistant S. aureus. Linezolid is an excellent and promising new antibiotic for
      the treatment of resistant Gram-positive pathogens.

PMID- 15482172
TI  - Can virulence factors be viable antibacterial targets?
AB  - There is a real crisis in healthcare with the emergence of bacterial pathogens
      resistant to multiple drugs. The drug discovery industry is faced with the
      challenge of developing new classes of antibiotics that are effective against
      resistant organisms. Targeting bacterial virulence is one approach that has yet
      to be fully exploited, and the last decade or so has seen the development of
      reagents, screens and approaches that could make this possible. Several processes
      utilized by bacteria to cause infection are employed in a wide range of pathogens
      and as such may make attractive targets. Inhibitors of such targets would be
      unlikely to affect host cells, be cross-resistant to existing therapies and
      induce resistance themselves.

PMID- 15482173
TI  - New trends in the management of tetanus.
AB  - The prevalence of tetanus reflects a failure of immunization. Prompt diagnosis
      and prediction of severity are crucial for the prevention of early life
      threatening complications and the institution of appropriate management. The
      current symptomatic treatment of heavy sedation, paralysis and artificial
      ventilation for 3-5 weeks for moderate and severe tetanus, is, even in the best
      centers, still associated with unacceptably high mortality, due to the disease
      and complications of the therapy itself. It is especially inappropriate for the
      developing world where intensive care resources are minimal. New options reported
      to avoid artificial ventilation and sedation are dantrolene (Dantrium, Procter
      and Gamble Pharmaceuticals), baclofen (Lioresal, Novartis) and magnesium.
      Magnesium therapy has the advantages of controlling spasms and sympathetic over
      activity without sedation. This simplifies nursing care and minimizes the need
      for ventilatory support except in the very severe disease and the elderly.
      Magnesium is recommended as the first-line therapy in tetanus.

PMID- 15482174
TI  - Sporotrichosis: a forgotten disease in the drug research agenda.
AB  - Potassium iodide was discovered in the 19th century and still remains as one of
      the more effective and most prescribed treatments for sporotrichosis. No new
      drugs have been evaluated in large randomized clinical trials in comparison with
      standard or alternative treatments for sporotrichosis during the last decades.
      The emergence of disseminated sporotrichosis in AIDS patients has uncovered the
      need for more effective treatments. Sporotrichosis is only a public health
      problem in a few geographical areas, mostly located in developing countries; and
      its usually harmless history could explain the limited investment in
      sporotrichosis treatment research. Better understanding of the virulence factors,
      such as the melanization process, could reveal new potential drug targets.

PMID- 15482175
TI  - Emerging trends in infections among renal transplant recipients.
AB  - Outcomes following renal and simultaneous kidney-pancreas transplants have
      improved significantly due to better surgical techniques and improved modalities
      of antirejection therapy. However, infection remains a significant cause of
      morbidity and mortality. The use of new modalities of immunosuppression and
      routine use of antimicrobial prophylaxis has changed the pattern of infections
      post-transplantation. Cytomegalovirus remains a significant problem and BK virus
      has emerged as an important pathogen. New antimicrobial agents are now available
      to treat infection, however, antimicrobial resistance remains a concern.

PMID- 15482176
TI  - Chronic cough in children: recent advances.
AB  - Recurrent cough in children is a very common symptom of respiratory disease. Most
      children who cough, however, have normal pulmonary function. This article
      presents a diagnostic framework for chronic cough and a recommended management
      plan in order to avoid over investigation and over treatment of a generally
      benign and self-remitting condition. Pathophysiology of cough and recent advances
      in treatment options are also included.

PMID- 15482177
TI  - Malaria chemoprophylaxis: when should we use it and what are the options?
AB  - Malaria chemoprophylaxis concerns prescribing healthy individuals medication for
      an infection they have an unknown chance of getting. Sensible use of malaria
      chemoprophylaxis is a balance between the risk of infection and death, and the
      risk of side effects. The risk of infection can be broken down into the risk of
      being bitten by a malaria-infected mosquito and the risk of the malaria parasites
      being resistant to the drug used for prophylaxis. Our knowledge of these
      parameters is patchy. The risk of infection is not uniform at a given location
      and the standard of living will greatly influence risk. It is suggested that
      chemoprophylaxis should not be recommended in areas with less than ten reported
      cases of P. falciparum malaria per 1000 inhabitants per year. The resistance
      pattern is known to a certain extent but, for instance, diverging opinion of how
      much resistance to chloroquine there is in West Africa illustrates the lack of
      data. There is much debate on rare adverse events, which usually escape Phase III
      studies prior to registration and are only picked up by passive, postmarketing
      surveillance. The lessons over the past 20 years with the introduction of
      amodiaquine, pyrimethamine/dapsone (Maloprim, GlaxoSmithKline) and
      pyrimethamine/sulfadoxine (Fansidar, Roche), which were all withdrawn for
      prophylaxis after a few years, show how sensitive drugs for chemoprophylaxis are
      to side effects. Three levels of chemoprophylaxis are used: chloroquine in areas
      with sensitive P. falciparum, chloroquine plus proguanil in areas with low level
      chloroquine resistance, and atovaquone/proguanil (Malarone, GlaxoSmithKline),
      doxycycline or mefloquine (Lariam, Roche) in areas with extensive resistance
      against chloroquine and proguanil. Primaquine and the primaquone analog
      tafenoquine may be future alternatives but otherwise there are few new drugs for
      chemoprophylaxis on the horizon.

PMID- 15482178
TI  - Hepatitis B mother--to--child transmission.
AB  - Approximately 350 million people are estimated to be chronically infected with
      hepatitis B virus, leading to an important public health problem. In highly
      endemic areas where 8 to 15% of people are chronically infected with hepatitis B
      virus, the risk for the neonate to be perinatally infected by the chronically
      infected mother, then to become chronically infected themselves, is very high. In
      those countries, the World Health Organization recommends hepatitis B vaccination
      systematically at birth, independent of hepatitis B virus maternal status. This
      vaccination program has begun to induce a rapid decrease in the number of acute
      hepatitis B virus infections and has also had a secondary effect of a decrease in
      related sequels. Lamivudine (Zeffix, GlaxoSmithKline), when associated with the
      immunization of the neonate, was recently demonstrated to dramatically reduce the
      residual risk of perinatal transmission. In intermediate and low endemicity
      areas, a systematic hepatitis B surface antigen screening is recommended during
      pregnancy, allowing, in the case of positivity, a selective hepatitis B virus
      neonate immunization during the first 12 h of life. Hepatitis B virus vaccination
      of children born to hepatitis B surface antigen-positive mothers confers long
      term immunity.

PMID- 15482179
TI  - The impact of the M184V substitution on drug resistance and viral fitness.
AB  - Treatment of HIV/AIDS with antiretroviral therapy can result in HIV-1 drug
      resistance, limiting its use. Resistance mutations arise prior to therapy due to
      errors in HIV-1 replication, and are also spread by sexual and other modes of
      transmission. However, it is also generally believed that resistance is due to
      multiple drug mutations to any single or combination of antiretroviral agents
      selected during viral replication in the presence of incompletely suppressive
      drug regimens. In the case of protease inhibitors and most nucleoside analog
      reverse transcriptase inhibitors, drug resistance is due to the accumulation of
      mutations in the HIV-1 protease and reverse transcriptase genes respectively.
      However, in the case of non-nucleoside reverse transcriptase inhibitors, a single
      primary drug mutation is usually sufficient to abrogate antiviral activity. This
      is also true of certain specific mutations, such as M184V in the reverse
      transcriptase enzyme, resulting in resistance to the nucleoside analog,
      lamivudine (Epivir, GlaxoSmithKline). However, it is thought that lamivudine may
      still contribute to the effectiveness of antiretroviral therapy, even after the
      appearance of the M184V mutation. M184V may affect sensitivity to other drugs,
      such as zidovudine (Retrovir, GlaxoSmithKline), in HIV-1 variants that already
      contain resistance mutations to zidovudine, during concomitant treatment with
      lamivudine. M184V also has a positive effect on HIV-1 RT fidelity, reducing
      spontaneous HIV mutagenesis. Processivity of the reverse transcriptase enzyme may
      be affected by mutations such as M184V, and this may be a major determinant of
      viral replication fitness.

PMID- 15482180
TI  - Management of anaerobic infection.
AB  - The management of anaerobic infection needs to be prompt and appropriate in order
      to ensure recovery. Management includes the use of hyperbaric oxygen, surgical
      methods and antimicrobial therapy. Various factors, such as efficacy, bacterial
      antimicrobial resistance, ability to reach appropriate antimicrobial levels at
      the infected site, toxicity and stability need to be taken into account in
      choosing antimicrobial agents. Some antimicrobials have poor activity against
      anaerobic bacteria. The more suitable agents include penicillins, cephalosporins,
      carbapenems, chloramphenicol, clindamycin, metronidazole, macrolides,
      glycopeptides, tetracyclines and quinolones.

PMID- 15482181
TI  - What do we mean by antibiotic resistance?

PMID- 15482182
TI  - GB virus C may improve survival in HIV-positive men.

PMID- 15482184
TI  - Lamivudine for chronic hepatitis B.
AB  - Lamivudine (Epivir, GlaxoSmithKline) was approved by the US Food and Drug
      Administration for the treatment of adult patients with chronic hepatitis B in
      1998, and has since been shown to be of benefit to selected patients with chronic
      hepatitis B. Drug resistance is the main issue encountered during therapy, with
      lamivudine resistant mutants emerging at a rate of approximately 15 to 30% per
      year of therapy. These mutants are associated with relapse of hepatitis, and
      occasionally hepatic decompensation. Despite this, therapeutic indications and
      guidelines for lamivudine therapy have now been drawn up, which indicate that
      lamivudine will be the first line therapy for hepatitis B e antigen-positive
      chronic hepatitis B patients, although its role in hepatitis B e antigen-negative
      patients remains controversial.

PMID- 15482185
TI  - Coartemether (artemether and lumefantrine): an oral antimalarial drug.
AB  - Coartemether (Riamet, Coartem, Novartis), a tablet formulation of artemether and
      lumefantrine, is a well-tolerated, fast-acting and effective blood schizontocidal
      drug that serves primarily in the treatment of uncomplicated falciparum malaria
      that is resistant to other antimalarials. Initial clinical-parasitological
      response relies mainly on the artemether component, while lumefantrine effects
      radical cure. The absorption of lumefantrine is poor during the fasting state,
      the normal condition in acutely ill malaria patients, but with return to normal
      diet it becomes adequate. This highlights the need for an appropriate adjustment
      of the dose regimen. In the area where Plasmodium falciparum shows the highest
      degree of multidrug resistance worldwide, the best results (99% cure) were
      obtained with a six-dose regimen given over 5 days. Extensive cardiological
      investigations have demonstrated the high cardiac safety of coartemether.

PMID- 15482186
TI  - Recent advances in the treatment of HIV/AIDS.
AB  - In industrialized countries, highly active antiretroviral therapy has resulted in
      significant reductions in morbidity and mortality in patients with HIV/AIDS. At
      the same time, the management of the HIV-infected individual has become
      exceedingly complex due to the increasing number of antiretroviral medications
      and resistance to them. New medications are needed that are effective against the
      drug-resistant virus. The key advances in the management of HIV/AIDS as seen
      through the eyes of a front-line HIV physician who has been actively involved in
      patient care, clinical drug trials and as an educator for the past 15 years will
      be discussed.

PMID- 15482187
TI  - Therapeutic options for human herpesvirus-8/Kaposi's sarcoma-associated
      herpesvirus-related disorders.
AB  - Human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus infection is
      associated with three proliferative disorders in immunocompromised patients -
      Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease.
      These disorders often develop in patients with advanced AIDS who present a number
      of therapeutic challenges, underscoring the importance of continuing efforts
      dedicated to basic and clinical research in this field. In the era of highly
      active antiretroviral therapy, the incidence of AIDS and Kaposi's sarcoma has
      considerably decreased, presumably due to enhanced anti-Kaposi's sarcoma
      associated herpesvirus immune responses, whereas the situation with primary
      effusion lymphoma and multicentric Castleman's disease is more complex. Based on
      advances in the understanding of Kaposi's sarcoma-associated herpesvirus-related
      disorders and availability of antiretroviral agents, current and future
      therapeutic approaches will be discussed.

PMID- 15482188
TI  - Optimization of antibiotic dosing schedules in the light of increasing antibiotic
      resistance.
AB  - The development of antibiotic-resistant bacteria is an increasing problem
      throughout the world and is, without doubt, due to the increasing use of
      antibiotics themselves. As organisms become more resistant, treatment options
      become more limited and treatment failures increasingly likely. The need to
      reverse, or at least minimize this pattern of increasing resistance is therefore
      essential. Numerous strategies to achieve this have been postulated and there is
      no doubt that a combination of these will ultimately prove to be most effective.
      Among them, using antibiotic dosing regimens that may be less likely to promote
      resistance is one measure which could be beneficial, and this will be the focus
      of this review. Individual antibiotics will be discussed under the headings of
      the patterns of killing activity that they produce. Namely whether they exhibit
      concentration-dependent killing with prolonged persistent effects, time-dependent
      killing with minimal or no persistent effects, or time-dependent killing with
      prolonged persistent effects. The available evidence for optimal dosing regimens,
      as far as minimizing antibiotic resistance is concerned, will be reviewed. Where
      possible, recommendations relating to clinical practice will be made, or failing
      that, an indication of where further research would be of benefit.

PMID- 15482190
TI  - Endobronchial tuberculosis.
AB  - Endobronchial tuberculosis is defined as tuberculous infection of the
      tracheobronchial tree. Although clinical features differ between various types
      and stages of endobronchial tuberculosis, common symptoms are cough, hemoptysis,
      sputum production, wheezing, chest pain, fever and dyspnea. Endobronchial
      tuberculosis is difficult to diagnose, because the lesion is not evident in the
      chest radiograph. Computerized tomography is very useful in evaluating bronchial
      lesions such as stenosis or obstruction. The most important goal of treatment in
      active endobronchial tuberculosis is the eradication of tubercle bacilli. The
      second most important goal is prevention of bronchial stenosis. Corticosteroid
      therapy for prevention of bronchial stenosis in endobronchial tuberculosis
      remains controversial, but the best results are associated with minimal delay in
      the initiation of steroid treatment. In inactive disease, treatment to restore
      full patency is appropriate. As steroids or other medication are unable to
      reverse stenosis from fibrous disease, airway patency must be restored
      mechanically by surgery or endobronchial intervention. Aerosol therapy with
      streptomycin and corticosteroids is useful in treatment against active
      endobronchial tuberculosis. Time to healing of ulcerous lesions is shorter, and
      bronchial stenosis is less severe in patients on aerosol therapy. Progression to
      bronchial stenosis may be prevented if the therapy is initiated as soon as
      possible.

PMID- 15482189
TI  - New antiviral therapies for hepatitis C.
AB  - Hepatitis C affects 170 million people worldwide and is the leading indication
      for liver transplantation. However, despite this high prevalence and burden of
      disease, current treatment regimens necessitate long durations of therapy, are
      often poorly tolerated and have suboptimal rates of sustained virologic response.
      Therefore, much attention has been directed at the development of new therapeutic
      agents against specific viral targets. This article reviews modifications of
      current therapies, outlines the viral life cycle and focuses on novel therapeutic
      agents currently being studied.

PMID- 15482191
TI  - Recent advances in antifungal pharmacotherapy for invasive fungal infections.
AB  - Invasive fungal infections carry significant morbidity and mortality. Candida
      species have become one of the most frequent causes of bloodstream infections,
      and infections caused by molds such as Aspergillus are becoming more frequent in
      immunocompromised patients. As this population grows, more invasive fungal
      infections can be anticipated. In the past, treatment options have been limited
      for many of these infections due to toxicity and efficacy concerns with the
      available antifungals. Fortunately, the past few years have brought exciting
      developments in antifungal pharmacotherapy. Lipid-based formulations of
      amphotericin B were introduced in the 1990s to attenuate adverse effects caused
      by amphotericin B deoxycholate (Fungizone, Bristol-Myers Squibb). Most recently,
      the echinocandins have been added to our antifungal regimen with the introduction
      of caspofungin (Cancidas, Merck and Co.) and voriconazole (Vfend, Pfizer), a new
      triazole, has come to market. The introduction of the echinocandins has
      invigorated the discussion about combination antifungal therapy. Evidence-based
      studies using these new agents are accumulating, and they are assuming important
      roles in the pharmacotherapy of invasive fungal infections in seriously ill and
      complex patients.

PMID- 15482192
TI  - New developments in antifungal strategy.
AB  - The increasing importance of invasive fungal infection as a cause of severe
      morbidity and mortality in immunocompromised patients has fuelled the development
      of new antifungal agents, including new triazole agents and echinocandins.
      Failure to diagnose fungal infection adequately has hampered the evaluation of
      these drugs in clinical trials. Consequently, the evidence base behind many
      prophylactic and empirical treatment strategies has been poor. Recent advances
      have improved diagnostic criteria and opened the way for more rational usage of
      these expensive preparations. The proven efficacy and improved safety profile of
      newer agents is a major advantage. Furthermore, better understanding of the
      immune response may allow novel strategies of adjunctive therapy and
      immunomodulation.

PMID- 15482193
TI  - Progress in the treatment of a neglected infectious disease: visceral
      leishmaniasis.
AB  - Visceral leishmaniasis (kala-azar) is a disseminated intracellular protozoal
      infection. Most cases (90%) occur in the rural regions of five countries: India,
      Sudan, Nepal, Bangladesh and Brazil. As with other infectious diseases embedded
      in high-level poverty, developing and/or delivering new treatments for visceral
      leishmaniasis had been painfully slow or nonexistent. However, despite persistent
      unresolved obstacles (e.g., drug affordability), renewed interest in visceral
      leishmaniasis and numerous successful treatment trials have combined to turn a
      therapeutic corner in the past 5 years, yielding new alternatives to conventional
      pentavalent antimony. Advances include the use of low-cost generic pentavalent
      antimony, rediscovery of amphotericin B, short-course regimens via lipid
      formulations of amphotericin B, retesting injectible paromyomycin and, of clear
      cut importance, identifying miltefosine (Impavido, Zentaris) as the first
      effective oral therapy for this neglected disease.

PMID- 15482194
TI  - Prevention and treatment of leptospirosis.
AB  - Leptospirosis is a common zoonosis acquired by exposure to body fluids, to
      tissues of infected animals, or to contaminated soil or fresh water. Large
      outbreaks of leptospirosis have occurred following excess rainfall or in tourists
      following exposure to fresh water during adventure activities. Prevention may be
      achieved through the use of protective clothing or by changes in animal
      husbandry. Immunization is not widely used in human populations but has a role in
      agriculture. Oral administration of doxycycline (Periostat , CollaGenex) once
      weekly can give short-term protection in high-risk environments. The disease in
      humans has a broad range of symptoms. Treatment may be symptomatic or may require
      administration of antibiotics, such as doxycycline or penicillin.

PMID- 15482195
TI  - Emerging infectious diseases: vulnerabilities, contributing factors and
      approaches.
AB  - We live in an ever more connected global village linked through international
      travel, politics, economics, culture and human-human and human-animal
      interactions. The realization that the concept of globalization includes global
      exposure to disease-causing agents that were formerly confined to small, remote
      areas and that infectious disease outbreaks can have political, economic and
      social roots and effects is becoming more apparent. Novel infectious disease
      microbes continue to be discovered because they are new or newly recognized, have
      expanded their geographic range, have been shown to cause a new disease spectrum,
      have jumped the species barrier from animals to humans, have become resistant to
      antimicrobial agents, have increased in incidence or have become more virulent.
      These emerging infectious disease microbes may have the potential for use as
      agents of bioterrorism. Factors involved in the emergence of infectious diseases
      are complex and interrelated and involve all classifications of organisms
      transmitted in a variety of ways. In 2003, outbreaks of interest included severe
      acute respiratory syndrome, monkeypox and avian influenza. Information from the
      human genome project applied to microbial organisms and their hosts will provide
      new opportunities for detection, diagnosis, treatment, prevention, control and
      prognosis. New technology related not only to genetics but also to satellite and
      monitoring systems will play a role in weather, climate and the approach to
      environmental manipulations that influence factors contributing to infectious
      disease emergence and control. Approaches to combating emerging infectious
      diseases include many disciplines, such as animal studies, epidemiology,
      immunology, ecology, environmental studies, microbiology, pharmacology, other
      sciences, health, medicine, public health, nursing, cultural, political and
      social studies, all of which must work together. Appropriate financial support of
      the public health infrastructure including surveillance, prevention,
      communication, adherence techniques and the like will be needed to support
      efforts to address emerging infectious disease threats.

PMID- 15482196
TI  - Global dissemination of beta-lactamases mediating resistance to cephalosporins
      and carbapenems.
AB  - While the main era of beta-lactam discovery programs is over, these agents
      continue to be the most widely prescribed antimicrobials in both community and
      hospital settings. This has led to considerable beta-lactam pressure on
      pathogens, resulting in a literal explosion of new beta-lactamase variants of
      existing enzyme classes. Recent advances in the molecular tools used to detect
      and characterize beta-lactamases and their genes has, in part, fueled the large
      increase in communications identifying novel beta-lactamases, particularly in
      Gram-negative bacilli. It now seems clear that the beta-lactams themselves have
      shaped the field of new enzymes, and the evolution of key amino acid
      substitutions around the active sites of beta-lactamases continues to drive
      resistance. Over 130 variants of TEM beta-lactamase now exist, and more are
      reported in the scientific literature each month. The most disturbing current
      trend is that many bla structural genes normally limited to the chromosome are
      now mobilized on plasmids and integrons, broadening the spread of resistance to
      include carbapenems and cephamycins. Furthermore, in some Enterobacteriaceae,
      concomitant loss of outer membrane porins act in concert with these transmissible
      beta-lactamase genes to confer resistance to the most potent beta-lactams and
      inhibitor combinations available. Continued reviews of the literature are
      necessary in order to keep abreast of the ingenuity with which bacteria are
      changing the current genetic landscape to confer resistance to this important
      class of antimicrobials.

PMID- 15482198
TI  - Canada contribute to the '3 by 5' AIDS treatment initiative.

PMID- 15482197
TI  - Antiretroviral therapy-induced immune restoration in HIV infection: a double
      edged sword?

PMID- 15482200
TI  - Micafungin: a therapeutic review.
AB  - In recent decades, the incidence of aspergillosis, candidiasis and clinically
      important deep mycoses has been increasing, with advances in transplantation
      medicine and anticancer chemotherapy. Micafungin (FK463, Fujisawa Healthcare) has
      been developed as a novel type of antifungal agent, which inhibits 1,3-beta-D
      glucan synthase in the fungal cell wall. Micafungin, one of the echinocandins,
      exhibits extremely high antifungal activity against Aspergillus spp. and Candida
      spp. in vitro. It is also characterized by a linear pharmacokinetic profile and a
      much lower prevalence of adverse reactions than amphotericin B. Micafungin is
      quite useful in the treatment of deep mycoses. In clinical studies in Japan,
      micafungin was found to be highly effective against aspergillosis (57.1% overall
      efficacy rate) and candidiasis (78.6%). Micafungin is expected to increase the
      efficacy rate of treatment in patients with severe aspergillosis or candidiasis
      when used in combination with amphotericin B or mold azoles.

PMID- 15482201
TI  - Fluconazole for the treatment of candidiasis: 15 years experience.
AB  - Candidia spp. are responsible for contributing to the increasing global
      prevalence of fungal infections. Fluconazole (Diflucan((R)), Pfizer) is a
      triazole that has established an exceptional therapeutic record for candida
      infections including oropharyngeal and esophageal candidiasis, vulvovaginal
      candidiasis, candidemia and disseminated candidiasis. It is both an oral and
      parenteral fungistatic agent that inhibits ergosterol synthesis in yeasts.
      Extensive clinical studies have demonstrated fluconazole's remarkable efficacy,
      favorable pharmacokinetics and reassuring safety profile, all of which have
      contributed to its widespread use. Fluconazole became the first antifungal with
      worldwide sales exceeding billions of dollars, therefore providing an incentive
      for the pharmaceutical industry to develop new antifungals. This review will
      examine the contributions and limitations of fluconazole in the treatment of
      superficial and invasive candidiasis syndromes.

PMID- 15482202
TI  - Nevirapine in the treatment of HIV.
AB  - Nevirapine (Viramune, Boehringer Ingelheim Ltd) is the first marketed non
      nucleoside reverse transcriptase inhibitor. As with any antiretroviral drug,
      nevirapine should always be used as part of a fully suppressive regimen. Clinical
      studies have shown that nevirapine-containing regimens may accomplish durable
      virological and immunological responses in approximately half of all
      antiretroviral-naive patients. It can also be successfully used as a component of
      salvage therapies and as a part of a strategy to simplify protease inhibitor
      containing regimens. Nevirapine has a beneficial effect on the lipid profile in
      both treatment-naive and -experienced patients. Nevirapine also has an important
      role in preventing mother-to-child transmission of HIV. It is usually well
      tolerated with rash and liver toxicity being the most frequently reported adverse
      events. Nevirapine interacts with cytochrome P450 enzymes both as a substrate and
      as an inducer. For this reason, therapeutic drug monitoring should be recommended
      whenever nevirapine is used with protease inhibitors, methadone (Methadose,
      Rosemont Pharmaceuticals Ltd), oral contraceptives, rifampicin (Rifadin, Aventis
      Pharma) and other potentially interacting drugs. Nevirapine-resistant mutations
      are common to the non-nucleoside reverse transcriptase inhibitor family and they
      include K103N, V106A, Y181C, Y188C and G190A. A better understanding of the
      nevirapine profile will certainly contribute to ensuring that its clinical
      application becomes more effective and beneficial.

PMID- 15482203
TI  - Hepatitis C drug discovery: in vitro and in vivo systems and drugs in the
      pipeline.
AB  - The combination therapy of ribavirin and pegylated interferon-alpha for hepatitis
      C has significant side effects, is often poorly tolerated and is ineffective in
      many patients, despite causing impressive improvement in the sustained
      virological response. Discovery and development of more effective and well
      tolerated antihepatitis C virus drugs are clearly in great demand. During the
      past few years, remarkable advances have been made in the establishment of in
      vitro and in vivo systems. Armed with these systems, a wave of specific
      antihepatitis C virus compounds have been discovered and are moving into the
      clinical phase. More effective combination therapies with specific antivirals are
      predicted to emerge in the near future for the treatment of hepatitis C.

PMID- 15482204
TI  - Overview of congenitally and perinatally acquired cytomegalovirus infections:
      recent advances in antiviral therapy.
AB  - Congenital and perinatal infection with human cytomegalovirus (CMV) are commonly
      encountered in newborns. In recent years there has been increased awareness of
      the disabilities that result from congenital CMV infection, which in turn has
      prompted interest in examining the potential efficacy of antiviral agents to
      prevent or ameliorate neurodevelopmental injury. Currently, there are three
      licensed systemic antivirals for the treatment of CMV: ganciclovir (Cytovene,
      Roche] and its prodrug valganciclovir [Valcyte, Roche); foscarnet (Foscavir,
      AstraZeneca); and cidofovir (Vistide, Pharmacia). A CMV-specific immunoglobulin
      is also available. Experience with these agents in the setting of congenital and
      perinatal CMV infection is very limited, but there are encouraging data from a
      controlled clinical trial indicating that ganciclovir therapy may be of value in
      limiting one form of neurodevelopmental injury caused by congenital infection,
      that of sensorineural hearing loss. Licensed antivirals for the treatment of CMV
      all share the common mechanism of targeting the viral DNA polymerase, but novel
      therapies that employ alternative modes of action are in development. Ultimately,
      the problem of perinatal CMV infection may be best controlled by the development
      of CMV vaccines, which could be administered to young women of childbearing age
      to help control this important public health problem.

PMID- 15482205
TI  - Novel and re-emerging respiratory infections.
AB  - Over the last decade a number of novel viral respiratory pathogens have appeared
      or been recognized. Most of these are zoonoses, which have the capacity to infect
      humans directly or via an intermediate host. All but metapneumovirus are known to
      have caused epidemics of severe disease and at least two (the severe acute
      respiratory syndrome-coronavirus and influenza H5N1) have the potential to cause
      global pandemics. Possible preventive measures and treatment options against
      these new diseases are discussed in this review.

PMID- 15482206
TI  - Manipulation of immunity to and pathology of respiratory infections.
AB  - Respiratory infections are the third leading cause of death worldwide and are a
      priority for vaccine development. Immune defence mechanisms are critical in
      recovery from most respiratory infections but the role of the immune system in
      causing bystander lung injury is not as well understood, and will be the focus of
      this review. Immune-mediated injury results from physical occlusion of the
      airways or the ensuing 'cytokine storm', which may spill over into the systemic
      circulation and cause devastating consequences. Respiratory pathogens employ
      numerous strategies to avoid detection by the immune system. One of these, the
      alteration of key surface determinants, makes the design of rational vaccines
      problematic. In the following review the immune compartments responsible for
      clinical lung disease are discussed, and current and novel strategies to reduce
      their potency are overviewed.

PMID- 15482207
TI  - Significance, management and prevention of Streptococcus agalactiae infection
      during the perinatal period.
AB  - The highest annual death rate during the first five decades of life occurs in the
      first year, particularly during the perinatal period between the onset of labor
      and 72 h after birth. Invasive bacterial disease evoking the severe inflammatory
      response syndrome is a leading cause of perinatal morbidity and mortality. Group
      B streptococcus (Streptococcus agalactiae) is the most important pathogen in this
      period of life, although the concept of intrapartum antimicrobial prophylaxis has
      impressively reduced the rate of culture-proven invasive infection in neonates.
      This strategy, however, has considerable limitations since group B streptococcus
      related stillbirths or prematurity and late-onset sepsis cannot be prevented.
      Moreover, the use of intrapartum antimicrobial prophylaxis has significantly
      increased the use of antibiotics during labor and therefore may select for
      intrapartum infections caused by other bacteria, including those resistant to
      antibiotics. Several advances in the development of vaccines and research on
      virulence factors and pathways involved in the immune response to group B
      streptococcus have been accomplished within the last years, including complete
      sequencing of the group B streptococcus genome. Development of effective vaccines
      and implementation of vaccination strategies will be one of the key challenges in
      the future for prevention of neonatal group B Streptococcus infections.

PMID- 15482208
TI  - Treatment of bullous impetigo and the staphylococcal scalded skin syndrome in
      infants.
AB  - Impetigo is a common, superficial, bacterial infection of the skin characterized
      by an inflamed and infected epidermis. The rarer variant, bullous impetigo, is
      characterized by fragile fluid-filled vesicles and flaccid blisters and is
      invariably caused by pathogenic strains of Staphylococcus aureus. Bullous
      impetigo is at the mild end of a spectrum of blistering skin diseases caused by a
      staphylococcal exfoliative toxin that, at the other extreme, is represented by
      widespread painful blistering and superficial denudation (the staphylococcal
      scalded skin syndrome). In bullous impetigo, the exfoliative toxins are
      restricted to the area of infection, and bacteria can be cultured from the
      blister contents. In staphylococcal scalded skin syndrome the exfoliative toxins
      are spread hematogenously from a localized source causing widespread epidermal
      damage at distant sites. Both occur more commonly in children under 5 years of
      age and particularly in neonates. It is important to swab the skin for
      bacteriological confirmation and antibiotic sensitivities and, in the case of
      staphylococcal scalded skin syndrome, to identify the primary focus of infection.
      Topical therapy should constitute either fusidic acid (Fucidin, Leo Pharma Ltd)
      as a first-line treatment, or mupirocin (Bactroban, GlaxoSmithKline) in proven
      cases of bacterial resistance. First-line systemic therapy is oral or intravenous
      flucloxacillin (Floxapen, GlaxoSmithKline). Nasal swabs from the patient and
      immediate relatives should be performed to identify asymptomatic nasal carriers
      of Staphylococcus aureus. In the case of outbreaks on wards and in nurseries,
      healthcare professionals should also be swabbed.

PMID- 15482209
TI  - Whooping cough due to Bordetella parapertussis: an unresolved problem.
AB  - Bordetella parapertussis is one of the bacteria that causes whooping cough.
      However, little attention has been paid to this bacterium because it causes a
      milder illness than Bordetella pertussis and the rate of detection is low, even
      though research suggests that pertussis vaccines have limited efficacy against B.
      parapertussis infection. However, recent studies have revealed high rates of
      detection in patients with whooping cough in some field studies. In this review,
      the relevant studies of B. parapertussis are summarized and it is demonstrated
      that it is now necessary to pay greater attention to infections by this
      bacterium.

PMID- 15482211
TI  - Mycobacterium tuberculosis: new tricks for an old bug.

PMID- 15482210
TI  - T-cell based vaccines: where are we?

PMID- 15482214
TI  - Adefovir dipivoxil in the treatment of chronic hepatitis B virus infection.
AB  - Adefovir dipivoxil (Hepsera, Gilead Sciences) is a prodrug of adefovir, with
      potent antiviral activity against hepatitis B virus. Adefovir dipivoxil therapy,
      10 mg daily for 48 weeks, is effective in hepatitis B e antigen-positive and 
      negative chronic hepatitis B. In hepatitis B e antigen-negative chronic hepatitis
      B, adefovir dipivoxil was recently found to maintain its efficacy even after 3
      years of therapy. Adefovir dipivoxil is effective in patients with compensated or
      decompensated chronic viral B liver disease, and in pre- and post-transplant
      hepatitis B virus patients who develop resistance to lamivudine (Epivir,
      GlaxoSmithKline). It is well-tolerated and safe even after the third year of long
      term therapy, and is associated with low rates of viral resistance. All these
      characteristics make adefovir dipivoxil an important drug for the treatment of
      hepatitis B virus infection and an excellent candidate for long-term maintenance
      therapy in chronic viral B liver disease.

PMID- 15482215
TI  - Voriconazole: therapeutic review of a new azole antifungal.
AB  - The new triazole antifungal, voriconazole (Vfend, Pfizer Ltd), was developed for
      the treatment of life-threatening fungal infections in immunocompromised
      patients. The drug, which is available for both oral and intravenous
      administration, has broad-spectrum activity against pathogenic yeasts, dimorphic
      fungi and opportunistic moulds. Unlike fluconazole (Diflucan, Pfizer Ltd),
      voriconazole has potent in vitro activity against Aspergillus spp., Fusarium spp.
      and Scedosporium apiospermum. In Phase II/III trials, voriconazole was well
      tolerated and had excellent clinical efficacy in patients with fluconazole
      sensitive and -resistant candida infection, aspergillosis, and various refractory
      fungal infections. The US Food and Drug Administration approved voriconazole in
      May 2002 for the treatment of invasive aspergillosis, and serious infections
      caused by Fusarium and S. apiospermum in patients who are intolerant of, or
      refractory to, other antifungal agents. In Europe, voriconazole is approved by
      the European Medicines Agency for the treatment of invasive aspergillosis,
      serious infections caused by Fusarium and S. apiospermum, and fluconazole
      resistant serious invasive candida infections (including C. krusei).

PMID- 15482216
TI  - Anidulafungin: review of a new echinocandin antifungal agent.
AB  - Anidulafungin (Vicuron Pharmaceuticals) is a new echinocandin antifungal with
      potent activity against Aspergillus and Candida spp. Anidulafungin is a
      noncompetitive inhibitor of (1,3)-beta-D-glucan synthase within fungal cells. The
      drug is rapidly distributed and steady-state concentrations are achieved after
      the first dose, when a loading dose of twice the daily maintenance dose is given
      on day 1. Drug biotransformation occurs via chemical degradation, with no hepatic
      metabolism or renal elimination. A favorable pharmacokinetic profile and lack of
      significant drug interactions suggest that patients can receive anidulafungin
      without dosage adjustments. These characteristics, in addition to comparable
      efficacy to fluconazole (Diflucan, Pfizer Ltd) in the treatment of esophageal
      candidiasis, support further investigation of its use in the treatment of
      systemic fungal infections caused by Candida and Aspergillus spp.

PMID- 15482217
TI  - A pathophysiological approach to antiretroviral therapy.
AB  - A discussion of the pathophysiology of HIV infection is important not only to
      understand both routine and novel therapeutic approaches, but also to appreciate
      the challenges of long-term control and viral eradication. This article will
      first briefly review certain pathophysiologic principles of HIV infection that
      have particular therapeutic implications, and then discuss general tenets of
      antiretroviral therapy, followed by new developments in the field.

PMID- 15482218
TI  - Prevention of HIV-associated opportunistic infections and diseases in the age of
      highly active antiretroviral therapy.
AB  - Since the introduction of highly active antiretroviral therapy (HAART), the rates
      of opportunistic infections have decreased markedly as has overall morbidity and
      mortality from HIV infection in developed countries. However, opportunistic
      infections remain the most important cause of death in HIV-infected people due to
      both late presentation of HIV infections and failure of HAART to adequately
      restore cell-mediated immunity in all individuals. While prophylaxis may be
      discontinued in patients who have responded to HAART with sustained increases of
      their CD4 counts above risk thresholds, for those patients who fail HAART, those
      who are unable to tolerate it, or whose treatments are interrupted, opportunistic
      infection prophylaxis remains essential. Some HIV-associated diseases, such as
      anogenital human papilloma virus-induced neoplasia and hepatitis C infection,
      have not decreased in frequency with the advent of HAART. For these conditions,
      effective screening and treatment programs will be necessary to prevent ongoing
      morbidity. This review will provide an update on HIV-associated opportunistic
      infections and their prevention in the age of HAART, as well as discuss novel
      presentations of opportunistic illnesses, such as immune restoration syndromes.

PMID- 15482219
TI  - Treatment of Lyme disease: a medicolegal assessment.
AB  - Lyme disease is the most common tick-borne disease in the world today. Despite
      extensive research into the complex nature of Borrelia burgdorferi, the
      spirochetal agent of Lyme disease, controversy continues over the diagnosis and
      treatment of this protean illness. This report will focus on two aspects of the
      treatment of Lyme disease. First, the medical basis for diagnostic and
      therapeutic uncertainty in Lyme disease, including variability in clinical
      presentation, shortcomings in laboratory testing procedures, and design defects
      in therapeutic trials. Second, the standard of care and legal issues that have
      resulted from the clinical uncertainty of Lyme disease diagnosis and treatment.
      Specifically, the divergent therapeutic standards for Lyme disease are addressed,
      and the difficult process of creating treatment guidelines for this complex
      infection is explored. Consideration by healthcare providers of the medicolegal
      issues outlined in this review will support a more rational approach to the
      diagnosis and treatment of Lyme disease and related tick-borne illnesses.

PMID- 15482220
TI  - Cytomegalovirus following stem cell transplantation: from pharmacologic to
      immunologic therapy.
AB  - Human cytomegalovirus is a large DNA virus that is well-equipped to evade both
      innate and adaptive host immune responses and to establish lifelong latency. It
      is a major opportunistic pathogen in immunocompromised hosts. Following
      allogeneic transplantation, immune responses are often inadequate to inhibit
      viral reactivation, resulting in progressive tissue damage, manifesting as overt
      human cytomegalovirus disease that usually presents as pneumonitis, colitis or
      hepatitis. Currently available antiviral pharmacotherapies are limited by
      toxicities if used prophylactically, and by a lack of efficacy in established
      human cytomegalovirus disease. Efforts have therefore focused on molecular
      diagnostic surveillance protocols that allow earlier intervention and the
      development of adoptive immunotherapeutic strategies to hasten host immune
      reconstitution.

PMID- 15482221
TI  - Treatment of staphylococcal scalded skin syndrome.
AB  - Humans are a natural reservoir for Staphylococcal aureus. Colonization begins
      soon after birth and predisposes to infection. S. aureus is one of the most
      common causes of skin infection, giving rise to folliculitis, furunculosis,
      carbuncles, ecthyma, impetigo, cellulitis and abscesses. In addition, S. aureus
      may cause a number of toxin-mediated life-threatening diseases, including
      staphylococcal scalded skin syndrome (SSSS). Epidermolytic toxins released by
      certain S. aureus strains cause SSSS by cleaving the epidermal cell adhesion
      molecule, desmogelin-1, resulting in superficial skin erosion. Recent experiments
      have revealed similarities in the pathophysiology of SSSS and pemphigus
      foliaceus, an autoimmune disorder that is characterized by antibodies targeting
      the same epidermal attachment protein. SSSS typically affects neonates and
      infants but may also occur in predisposed adults. It is painful and distressing
      for the patient and parents, although most cases respond to antibiotic treatment.
      Mortality is low in infants but can be as high as 67% in adults, and is dependent
      on the extent of skin involvement and the comorbid state. Thus, the management of
      adults who develop SSSS remains a major therapeutic challenge. The antibody
      response against the toxins neutralizes their effect and prevents recurrence or
      limits the effects to the area of infection, which is known as bullous impetigo.

PMID- 15482222
TI  - Tuberculosis in pregnancy: current recommendations for screening and treatment in
      the USA.
AB  - The main focus of this review is the management of active and latent tuberculosis
      in pregnancy in industrialized countries. The review is geared towards the
      healthcare professional taking care of the obstetric patient. The epidemiology of
      active and latent tuberculosis in the USA and recommendations for the screening
      of tuberculosis in pregnancy are considered. The history of treatment methodology
      and its relationship to the current treatment of active and latent tuberculosis
      in pregnancy is reviewed, and finally, a discussion of the best time to treat
      latent tuberculosis in a pregnant patient is undertaken, along with thoughts on
      future changes and advances in this field.

PMID- 15482223
TI  - Helicobacter pylori infection: diagnosis and treatment.
AB  - Helicobacter pylori is one of the most common infections worldwide. Eradication
      of this important pathogen would lead to virtual elimination of the second most
      common cancer worldwide - gastric cancer. A variety of accurate diagnostic tests
      are available but current therapeutic regimens are generally unsatisfactory, with
      failure rates of between 20 and 40%. Difficulty in curing the infection has led
      to a three-step approach: diagnosis, therapy and confirmation of cure. Better
      studies, including head-to-head comparison of different drugs, drug formulations,
      dosing intervals, dosing in relation to meals, and duration of therapy are
      needed. The high rates of reinfection and the lack of improvements in standards
      of living in developing countries makes the development of a vaccine a high
      priority.

PMID- 15482224
TI  - Chronic Pseudomonas aeruginosa infection in cystic fibrosis airway disease:
      metabolic changes that unravel novel drug targets.
AB  - The cystic fibrosis (CF) airways have an incompletely characterized defect in
      innate defense that eventually leads to bacterial infection and airway
      inflammation. Persistent Pseudomonas aerugionsa infection resulting from
      defective innate immunity and a bacterial phenotypic switch to a more intractable
      mucoid form inside the airway are now well established as important components of
      CF pathogenesis. Broad-based factors leading to chronic infection will be
      discussed with respect to: bacterial virulence in the context of biofilm
      formation, quorum sensing machinery and alginate overproduction, and failure of
      innate lung immunity in CF airways. In addition, a controversial question as to
      whether inflammation or infection comes first during CF airway disease will be
      addressed. Finally, a new hypothesis, that P. aeruginosa thrives as biofilms
      within the thickened anaerobic mucus layers, will be developed.

PMID- 15482226
TI  - Antimicrobial resistance in respiratory tract pathogens.
AB  - Antimicrobial resistance has been a problem ever since the introduction of
      antimicrobial agents 60 years ago. Today, this problem is increasing so rapidly
      that the end of the antimicrobial era is being predicted. The increasing problems
      caused by antimicrobial resistance can be illustrated by those seen in bacterial
      pathogens that cause community acquired respiratory tract infections, which are
      among the most common and important infections seen by clinicians. Bacterial
      pathogens causing community acquired respiratory tract infections have a number
      of resistance mechanisms such as beta-lactamases. Recognition of these resistance
      mechanisms allows them to be targeted, such as with beta-lactamase inhibitors.
      Newly recognized resistance mechanisms such as efflux may also be targeted in the
      future.

PMID- 15482225
TI  - In search of a small-molecule inhibitor for respiratory syncytial virus.
AB  - Respiratory syncytial virus has been an ongoing health problem for 50 years.
      Hospitalization rates due to virus-induced respiratory illness continue to be
      substantial for infants, small children, the elderly and the immunocompromised.
      The only currently available treatments are a broad-spectrum antiviral and two
      immunoprophylactic antibodies, all of which are reserved for high-risk patients.
      The combination of this limited therapeutic repertoire and the lack of a vaccine
      clearly demonstrates the need to continue the search for more efficacious and
      safe agents against respiratory syncytial virus. The following is a review on the
      current progress of that search.

PMID- 15482227
TI  - Areas of uncertainty in the management of human trichinellosis: a clinical
      perspective.
AB  - There is disagreement between authorities on most facets of trichinellosis
      therapy. The most controversial issues are when to use corticosteroids and which
      antihelminthic drug should be administered, for how long and at what dose. These
      issues are particularly important in the treatment of severe, potentially fatal
      infections. A major reason for the lack of consensus regarding trichinellosis
      management is that there have been very few prospective, controlled clinical
      trials of this infection. After a brief review of pertinent epidemiological and
      clinical features of the disease, selected treatment concerns will be discussed
      and areas where more information is urgently required will be highlighted.

PMID- 15482228
TI  - The changing face of virology: will the application of molecular techniques
      inevitably lead to new and better vaccines?

PMID- 15482229
TI  - HIV replication faster than previously thought.

PMID- 15482231
TI  - Efavirenz for HIV-1 infection in adults: an overview.
AB  - Efavirenz (Sustiva), Bristol-Myers Squibb) is a non-nucleoside reverse
      transcriptase inhibitor that has been used successfully since the late 1990s to
      treat HIV-1 infection, and has since become a cornerstone of antiretroviral
      therapy. The efficacy and potency of efavirenz has been established in many
      clinical trials and cohort studies, where it has been compared with unboosted or
      ritonavir (Norvir, Abbott Laboratories Ltd)-boosted protease inhibitors,
      nevirapine (Viramune, Boehringer Ingelheim Ltd); and three nucleoside analog
      based regimens. Pharmacokinetics allowing for a convenient once-daily
      administration make efavirenz one of the first agents to be included in once
      daily regimens. Tolerability of efavirenz is satisfactory, although CNS-related
      toxicity can occur, and is still poorly understood. New insights into the
      pharmacokinetics of efavirenz could help to manage this unwanted toxicity. This
      drug profile will examine the principal data concerning the efficacy,
      pharmacokinetics and safety that have made efavirenz a standard of care in HIV-1
      therapy, and will comment on new data that could change the way efavirenz is used
      in the near future.

PMID- 15482232
TI  - Telithromycin.
AB  - Telithromycin (Ketek), Aventis Pharma), a ketolide, belongs to a new class of
      antibiotics that was developed for the treatment of upper and lower respiratory
      tract infections. The prevalence of penicillin and macrolide resistance among
      respiratory pathogens is increasing in the USA. Telithromycin is highly active
      against beta-lactam, macrolide and fluoroquinolone reduced-susceptibility
      pathogens. Its efficacy has been shown to be equal or superior to comparator
      agents in numerous studies. It has a broad in vitro spectrum versus usual
      respiratory pathogens and oral once-daily dosing that increases patient
      compliance. Telithromycin penetrates rapidly into neutrophils in bronchopulmonary
      tissue, with peak levels obtained in 1 to 2 h. Results of clinical trials show
      clinical-esponse rates similar to comparator agents. The most frequent adverse
      events involve the gastrointestinal system, with mild to moderate diarrhea and
      nausea. A low rate of discontinuation was observed in the studies. Telithromycin
      is an effective first-line treatment for mild to moderate respiratory infections
      in adults.

PMID- 15482233
TI  - Tinidazole: from protozoa to Helicobacter pylori--the past, present and future of
      a nitroimidazole with peculiarities.
AB  - Tinidazole (Fasigyn, Pfizer Ltd), like metronidazole - to which it is
      structurally related - was initially introduced for treating protozoal
      infections. However, both of these nitroimidazole compounds are active against
      most clinically important obligate anaerobes. In the last few years, the
      discovery of Heliobacter pylori and of its susceptibility to nitroimidazoles
      focused new attention on these drugs. Tinidazole, as a part of this class of
      drugs, shares the characteristics and indications of other nitroimidazoles.
      However, it has a number of desirable features that could potentially make it
      very successful: a better pharmacokinetic and pharmacodynamic profile, a better
      safety and tolerability spectrum, and a preserved activity against some bacteria
      that are resistant to metronidazole.

PMID- 15482234
TI  - Inhibition of HIV-1 reverse transcription: basic principles of drug action and
      resistance.
AB  - Nucleoside and non-nucleoside analog inhibitors of HIV Type 1 reverse
      transcriptase are currently used in the clinic to treat infection with this
      retrovirus. Following their intracellular activation, nucleoside analogs act as
      chain terminators, while non-nucleoside analog reverse transcriptase inhibitors
      bind to a hydrophobic pocket in close proximity to the active site and inhibit
      the catalytic step. Compounds that belong to the two different classes of drugs
      are frequently administered in combination to take advantage of the different
      mechanisms of drug action. However, the development of drug resistance may occur
      under conditions of continued, residual viral replication, which is a major cause
      of treatment failure. This review addresses the interaction between different
      inhibitors and resistance-conferring mutations in the context of combination
      therapy with drugs that target the reverse transcriptase enzyme. Focus is placed
      on biochemical mechanisms and the development of future approaches.

PMID- 15482235
TI  - Antiretroviral therapy and mother-to-child transmission of HIV-1.
AB  - The advent of highly active antiretroviral therapy has facilitated the virtual
      elimination of mother-to-child transmission of HIV infection in developed
      countries, reducing transmission rates to approximately 1 to 2%. In these
      settings, highly active antiretroviral therapy has also transformed pediatric HIV
      infection into a chronic disease; although there are associated costs in terms of
      side effects and the heavy pill burden. In less developed settings, easier-to-use
      adaptations of antiretroviral therapy regimens, such as short-course and single
      dose antiretroviral strategies or neonatal postexposure prophylaxis can also
      substantially prevent mother-to-child transmission, although to a lesser degree
      than highly active antiretroviral therapy. However, postnatal transmission of
      infection through breastfeeding significantly reduces the longer-term efficacy of
      these strategies. Ongoing research is focusing on the use of antiretroviral
      therapy in the breastfeeding period.

PMID- 15482236
TI  - Treatment of HIV infection in the older patient.
AB  - The number of HIV patients over the age of 50 years is increasing due to
      increased longevity in patients treated with highly active antiretroviral therapy
      (HAART), in addition to new primary infections in older patients. Numerous
      studies have demonstrated worse HIV disease progression and mortality in older
      HIV patients compared with younger patients. While HAART therapy has been shown
      to be effective at reducing HIV-1 RNA, the immunologic benefits in older patients
      may be reduced compared to younger patients. Older patients are more likely to
      suffer comorbidities requiring concomitant medications than younger patients.
      Toxicities from HAART, particularly dyslipdemia, insulin resistance, and
      pancreatitis may also be worse in older HIV patients. Controlled trials on
      epidemiology, pathogenesis, and therapeutic and clinical outcomes in the elderly
      are needed. As the HIV-infected population ages, there is a growing need to
      better determine the efficacy of HAART in older patients, and to investigate
      factors associated with a more rapid course of HIV infection in patients over the
      age of 50 years.

PMID- 15482237
TI  - Current therapies for chronic hepatitis B virus infection.
AB  - Patients who are chronically infected with the hepatitis B virus are at an
      increased risk of developing cirrhosis, hepatic decompensation and hepatocellular
      carcinoma. Therapeutic intervention offers the only means of interrupting this
      progression. Currently there are three licensed agents for the treatment of
      chronic hepatitis B virus infection. These are interferon-alpha, an
      immunomodulator, and two synthetic nucleos(t)ide analogs, namely lamivudine
      (Epivir, GlaxoSmithKline) and adefovir dipivoxil (Hepsera, Gilead Sciences). This
      review aims to summarize current experience with these drugs in the treatment and
      management of patients with chronic hepatitis B virus infection, their efficacy,
      and current problems of drug resistance. An outline of future treatment
      perspectives is also included.

PMID- 15482238
TI  - Antimicrobial prophylaxis in solid-organ transplantation.
AB  - Solid-organ transplantation has become a widely accepted treatment modality for
      end-stage diseases. With the advent of newer and more potent immunosuppressive
      regimens, graft survival has improved, but at the expense of an increased risk
      for the development of infections secondary to bacterial, fungal, viral and
      parasitic pathogens. Prevention of such infectious complications with effective,
      well-tolerated and cost-effective antimicrobials would be ideal to improve the
      outcome of transplant patients. Cytomegalovirus is the most common cause of viral
      infections. Herpes simplex virus, Varicella-zoster virus, Epstein-Barr virus and
      others are also significant pathogens. Fungal infections are associated with the
      highest mortality rates. This review summarizes the most relevant data pertaining
      to the current understanding of infection prevention for solid-organ transplant
      recipients.

PMID- 15482239
TI  - Approaches to the management of uncomplicated genital Chlamydia trachomatis
      infections.
AB  - Genital chlamydial infection remains a highly prevalent sexually transmitted
      infection in the USA. A multifaceted approach to the management of chlamydial
      infection is essential to ensure cure and prevention of reinfection. This article
      will review current approaches to the management of uncomplicated genital
      chlamydial infection, discussing: the pathogen; antimicrobials that are and are
      not recommended for therapy by the US Centers for Disease Control and Prevention;
      partner treatment; follow-up; antimicrobial resistance; and potential future
      therapies.

PMID- 15482240
TI  - Kingella kingae infections of the skeletal system in children: diagnosis and
      therapy.
AB  - As the result of improved bacteriological techniques, Kingella kingae is emerging
      as an important cause of infections of the skeletal system in children younger
      than 2 years of age. This review details the bacteriological features and
      detection methods of this pathogen, as well as the epidemiology, clinical
      presentation, treatment and prognosis of septic arthritis, osteomyelitis and
      diskitis caused by the organism.

PMID- 15482241
TI  - Infection control in the intensive care unit.
AB  - Nosocomial infections are common in many hospital departments, but particularly
      so on the intensive care unit, where they affect some 20 to 30% of patients.
      While early diagnosis and appropriate treatment are, of course, important,
      perhaps the greatest challenge is in the application of techniques to limit the
      development of such infections. This review will briefly discuss some of the
      background pathophysiology and epidemiology of nosocomial infection, and then
      focus on general and infection-specific preventative strategies individually and
      as part of broader infection-control programs with infection surveillance.

PMID- 15482243
TI  - Is education immune from evidence-based scrutiny?

PMID- 15482244
TI  - Assessment of neurological status in preterm infants in neonatal intensive care
      and prediction of cerebral palsy.
AB  - The purpose of this study was to determine the diagnostic accuracy of a
      neurological assessment performed before discharge from the nursery to predict
      cerebral palsy at three years of age in preterm infants. Infants born < 31 weeks
      gestation between 1992 and 1996 were assessed using the Lacey Assessment of the
      Preterm Infant (LAPI) prior to discharge. Infants were classified as having no
      abnormality, possible abnormality, or definite abnormality. At three years of
      age, the infants had a neurological examination. Infants were stratified into
      those assessed at < or = 33 weeks postmenstrual age and those assessed at least
      once > 33 weeks postmenstrual age. Of the 203 infants, 36 were diagnosed with
      cerebral palsy at three years. Seven were assessed < or = 33 postmenstrual age
      and 29 were assessed > 33 weeks postmenstrual age. For infants assessed < or = 33
      weeks and classified as having any abnormality (possible or definite), the LAPI
      had 86% sensitivity, 83% specificity, and 96% negative predictive value for
      subsequent cerebral palsy. The LAPI was less accurate when applied to infants <
      33 weeks postmenstrual age. The LAPI is an accurate diagnostic tool in the
      preterm period for the prediction of normal motor development or cerebral palsy
      at three years of age. This information may be used to target intervention.

PMID- 15482245
TI  - Ultrasound and laser therapy in the treatment of carpal tunnel syndrome.
AB  - This study was designed to compare the efficacy of ultrasound and laser treatment
      for mild to moderate idiopathic carpal tunnel syndrome. Ninety hands in 50
      consecutive patients with carpal tunnel syndrome confirmed by electromyography
      were allocated randomly in two experimental groups. One group received ultrasound
      therapy and the other group received low level laser therapy. Ultrasound
      treatment (1 MHz, 1.0 W/cm(2), pulse 1:4, 15 min/session) and low level laser
      therapy (9 joules, 830 nm infrared laser at five points) were applied to the
      carpal tunnel for 15 daily treatment sessions (5 sessions/week). Measurements
      were performed before and after treatment and at follow up four weeks later, and
      included pain assessment by visual analogue scale; electroneurographic
      measurement (motor and sensory latency, motor and sensory action potential
      amplitude); and pinch and grip strength. Improvement was significantly more
      pronounced in the ultrasound group than in low level laser therapy group for
      motor latency (mean difference 0.8 m/s, 95% CI 0.6 to 1.0), motor action
      potential amplitude (2.0 mV, 95% CI 0.9 to 3.1), finger pinch strength (6.7 N,
      95% CI 5.0 to 8.2), and pain relief (3.1 points on a 10-point scale, 95% CI 2.5
      to 3.7). Effects were sustained in the follow-up period. Ultrasound treatment was
      more effective than laser therapy for treatment of carpal tunnel syndrome.
      Further study is needed to investigate the combination therapy effects of these
      treatments in carpal tunnel syndrome patients.

PMID- 15482246
TI  - Predisposing factors for occasional and multiple falls in older Australians who
      live at home.
AB  - This study, which was part of a larger study on the Health Status of Older People
      conducted in Melbourne, Australia, aimed to identify factors that discriminate
      between multiple and occasional falls amongst older people living at home. It
      used a survey of 1000 Australians aged 65 years and over. Subjects were
      classified as multiple fallers (two or more falls in the past year), occasional
      fallers (one fall in the past year), or non-fallers. Twenty-nine percent of older
      people who lived at home reported falling once or more in the previous 12 months.
      Nearly 20% of older people fell once in the previous 12 months and just under 10%
      fell more than once. Occasional fallers were more likely to be women (OR 1.75,
      95% CI 1.26 to 2.45), to have reported back pain (OR 1.54, 95% CI 1.10 to 2.16)
      and were nearly twice as likely to have more than three medical conditions
      compared to non-fallers (OR 1.88, 95% CI 1.22 to 2.90). Multiple fallers were
      also more likely to be women (OR 1.61, 95% CI 1.03 to 2.51). More multiple
      fallers (17%) than occasional fallers (9%) reported being very afraid of falling.
      Intervention strategies should take into account these differing predisposing
      factors for multiple and occasional falls.

PMID- 15482247
TI  - A six-week, resource-efficient mobility program after discharge from
      rehabilitation improves standing in people affected by stroke: placebo
      controlled, randomised trial.
AB  - Although intervention is effective in reducing the disability associated with
      stroke, limited resources mean that physiotherapy services often cease by six
      months after stroke. The purpose of this clinical trial was to investigate the
      efficacy of resource-efficient physiotherapy services in improving mobility and
      quality of life after stroke. Twenty-six people with residual walking
      difficulties after stroke were randomised into an experimental or control group
      after discharge from physiotherapy services. The experimental group participated
      in a six-week, home-based mobility program. The control group participated in a
      six-week, home-based program of upper-limb exercises (i.e. 'sham' mobility
      exercises). Subjects met with the therapist for prescription of exercises only
      three times during the six weeks. Strategies used to offset potential problems
      associated with minimal subject-therapist interaction included videotaped
      instructions to encourage correct performance of exercises, modification of the
      environment and involvement of carers to enhance safety, and telephone contact
      and self-monitoring to promote compliance. Standing (Functional Reach), walking
      (MAS Item 5) and quality of life (SA-SIP30) were measured prior to, immediately
      after, and two months after intervention ceased by an assessor who was blinded to
      group allocation. Subjects in the experimental group demonstrated significant
      improvement in standing compared to the control group (p = 0.01) which was
      maintained two months after the cessation of intervention (p = 0.04). There was
      no difference between the groups in walking (p = 0.50) or quality of life (p =
      0.70). The six-week, resource-efficient mobility program was effective in
      improving some of the mobility in people after discharge from stroke
      rehabilitation. The provision of resource-efficient programs is recommended
      wherever possible so that people affected by stroke may continue rehabilitation
      for longer.

PMID- 15482248
TI  - Dyspnoea in COPD: can inspiratory muscle training help?
AB  - Chronic obstructive pulmonary disease (COPD) is a progressive, common and costly
      condition. Dyspnoea frequently limits activity and reduces health-related quality
      of life. In addition to impaired lung function, peripheral muscle deconditioning
      and respiratory muscle dysfunction also contribute to dyspnoea and reduced
      exercise capacity. Pulmonary rehabilitation using whole body exercise training
      improves peripheral muscle function and reduces dyspnoea but does not improve
      respiratory muscle function. Providing that adequate training intensities are
      utilised, specific loading of the inspiratory muscles with commercially available
      hand-held devices can improve inspiratory muscle strength and endurance. Several
      studies have investigated the effects of inspiratory muscle training on dyspnoea
      in COPD subjects. Results of these studies are conflicting, most likely
      reflecting methodological shortcomings including insufficient training load,
      insensitive outcome measures, and inadequate statistical power. This paper
      describes the origin of dyspnoea in COPD, with particular attention given to the
      role of inspiratory muscle dysfunction in its genesis and its possible
      amelioration through inspiratory muscle training.

PMID- 15482249
TI  - Conclusions are compromised by lack of methodological quality. (Comment on Hayes
      et al, Australian Journal of Physiotherapy 50: 77-83).

PMID- 15482250
TI  - WCPT no longer requires 1000 hours clinical experience.

PMID- 15482252
TI  - Regulation of antigen-specific regulatory T-cell induction via nasal and oral
      mucosa.
AB  - With the identification of regulatory T cells (Tr), the hunt for ways to
      specifically intervene in ongoing inflammatory responses has grown exponentially.
      Tr are attractive for therapy because they have the potential to control
      deleterious responses while preserving normal immune function. It has long been
      known that application of soluble antigen via the mucosa induces mucosal Tr that
      preserve systemic tolerance upon challenge with the same antigen. Mucosal Tr
      exhibit three major properties that allow selective control of immune responses.
      They are (1) adaptive-that is, they differentiate from naive T cells in the
      periphery; (2) antigen-specific-that is, specific for the (exogenous) antigen
      applied via the mucosa; and (3) versatile-that is, suppress, irrespective of
      ongoing Th1 or Th2 cytokine polarization. These powerful characteristics provide
      mucosal Tr with all requirements necessary to selectively interfere in an
      unbalanced immune system, as occurs in diseases ranging from autoimmunity to
      transplant rejection and allergy. Until now, however, translation into clinical
      applications has led to moderate success. This is primarily due to limited
      knowledge about the fundamental characteristics of these cells because of the
      lack of a differential marker. The initial stages of mucosal Tr induction, which
      may hold the key to discovering the identity of mucosal Tr and unraveling their
      function, are discussed in this review.

PMID- 15482253
TI  - From pattern recognition receptor to regulator of homeostasis: the double-faced
      macrophage mannose receptor.
AB  - The mannose receptor (MR) is an endocytic and phagocytic receptor belonging to
      the C-type lectin superfamily. A number of functions have been ascribed to this
      receptor, which is involved in innate and adaptive immune responses. The MR binds
      carbohydrate moieties on several pathogens, such as bacteria, fungi, parasites,
      and viruses, and, therefore, is considered a pattern recognition receptor (PRR).
      In addition, MR binds endogenous molecules and was originally described as a
      membrane-associated component binding lysosomal glycosidases in alveolar
      macrophages. Since its identification more than 25 years ago, many other
      endogenous ligands were described, including hormones, enzymes, cell membranes,
      extracellular matrix components, and normal as well as tumoral mucins. The MR is
      preferentially expressed on immune cells of myeloid lineage, especially subsets
      of dendritic cells (DC) and tissue macrophages. In addition to immune cells,
      specialized endothelial cells are also MR-positive. Increasing evidence shows
      that the MR is involved in the silent clearance of inflammatory molecules. In
      this review, we discuss current knowledge about the receptor and show that
      endogenous ligands activate an anti-inflammatory and tolerogenic program in DC
      and macrophages, thus reinforcing the hypothesis that the MR has an important
      role in the maintenance of homeostasis.

PMID- 15482254
TI  - The role of Dectin-1 in antifungal immunity.
AB  - beta-Glucans are structural components of fungal cell walls, which have a
      stimulatory effect on the immune system. Although a number of receptors for these
      carbohydrates have been proposed, the recently identified C-type lectin-like
      receptor, Dectin-1, appears to play a central role. Dectin-1 is expressed on
      phagocytic cells, including macrophages and neutrophils, and mediates both the
      internalization and cellular responses to beta-glucan, through unique mechanisms.
      Dectin-1 can recognize and respond to live fungal pathogens and is being
      increasingly appreciated as having a key role in the innate responses to these
      pathogens. In addition to its exogenous ligands, Dectin-1 can recognize an
      unidentified endogenous ligand on T cells and may act as a co-stimulatory
      molecule, although its function in these responses is less clear. This review
      will highlight the current knowledge of Dectin-1 and its potential role in
      antifungal immunity, as well as deficiencies in our understanding.

PMID- 15482255
TI  - C and CX3C chemokines: cell sources and physiopathological implications.
AB  - Within the fascinating world of chemokines, C and CX3C chemokines have long been
      regarded as two minor components, even though they present unique features and
      show less redundancy than the other chemokine families. Nevertheless, the body of
      data on their expression and role in various inflammatory disorders has grown in
      the past few years. The C chemokine family is represented by two chemokines,
      XCL1/lymphotactin-alpha and XCL2/lymphotactin-beta, whereas the CX3C chemokine
      family contains only one member, called CX3CL1/ fractalkine. In this review, we
      present an overview on the structure, expression and signaling properties of
      these chemokines and their respective receptors and examine how they contribute
      to inflammation and the regulation of leukocyte trafficking, as well as their
      potential role in the pathophysiology of human inflammatory diseases. Taken
      together, these data expand the biological importance of C and CX3C chemokines
      from that of simple immune modulators to a much broader biological role, even
      though their precise commitment within the framework of immune responses has
      still to be determined.

PMID- 15482256
TI  - Examination of mitochondrial protein targeting of haem synthetic enzymes: in vivo
      identification of three functional haem-responsive motifs in 5-aminolaevulinate
      synthase.
AB  - The initial and the terminal three enzymes of the mammalian haem biosynthetic
      pathway are nuclear encoded, cytoplasmically synthesized and post-translationally
      translocated into the mitochondrion. The first enzyme, ALAS (5-aminolaevulinate
      synthase), occurs as an isoenzyme encoded on different chromosomes and is
      synthesized either as a housekeeping protein (ALAS-1) in all non-erythroid cell
      types, or only in differentiating erythroid precursor cells (ALAS-2). Both ALAS
      proteins possess mitochondrial targeting sequences that have putative haem
      binding motifs. In the present study, evidence is presented demonstrating that
      two haem-binding motifs in the leader sequence, as well as one present in the N
      terminus of the mature ALAS-1 function in vivo in the haem-regulated
      translocation of ALAS-1. Coproporphyrinogen oxidase, the antepenultimate pathway
      enzyme, possesses a leader sequence that is approx. 120 residues long. In
      contrast with an earlier report suggesting that only 30 residues were required
      for translocation of the coproporphyrinogen oxidase, we report that the complete
      leader is necessary for translocation and that this process is not haem-sensitive
      in vivo. PPO (protoporphyrinogen oxidase) lacks a typical mitochondrial targeting
      leader sequence and was found to be effectively targeted by just 17 N-terminal
      residues. Bacillus subtilis PPO, which is very similar to human PPO at its N
      terminal end, is not targeted to the mitochondrion when expressed in mammalian
      cells, demonstrating that the translocation is highly specific with regard to
      both the length and spacing of charged residues in this targeting region.
      Ferrochelatase, the terminal enzyme, possesses a typical N-terminal leader
      sequence and no evidence of a role for the C-terminus was found in mitochondrial
      targeting.

PMID- 15482257
TI  - Determination of the minimal functional ligand-binding domain of the GABAB1b
      receptor.
AB  - In the mammalian central nervous system, slow inhibitory neurotransmission is
      largely mediated by metabotropic GABA(B) receptors (where GABA stands for gamma
      aminobutyric acid), which belong to the G-protein-coupled receptor gene family.
      Functional GABA(B) receptors are assembled from two subunits GABA(B1) (GABA(B)
      receptor subtype 1) and GABA(B2). For the GABA(B1) subunit, which binds the
      neurotransmitter GABA, two variants GABA(B1a) (GABA(B) receptor subtype 1 variant
      a) and GABA(B1b) have been identified. They differ at the very N-terminus of
      their large glycosylated ECD (extracellular domain). To simplify the structural
      characterization, we designed truncated GABA(B1) receptors to identify the
      minimal functional domain which still binds a competitive radioligand and leads
      to a functional, GABA-responding receptor when co-expressed with GABA(B2). We
      show that it is necessary to include all the portion of the ECD encoded by exon 6
      to exon 14. Furthermore, we studied mutant GABA(B1b) receptors, in which single
      or all potential N-glycosylation sites are removed. The absence of
      oligosaccharides does not impair receptor function, suggesting that the
      unglycosylated ECD of GABA(B1) can be used for further functional or structural
      investigations.

PMID- 15482258
TI  - Activation of ryanodine receptors induces calcium influx in a neuroblastoma cell
      line lacking calcium influx factor activity.
AB  - We have further characterized the Ca2+ signalling properties of the NG115-401L
      (or 401L) neuroblastoma cell line, which has served as an important cell line for
      investigating SOC (store-operated channel) influx pathways. These cells possess
      an unusual Ca2+ signalling phenotype characterized by the absence of Ca2+ influx
      when Ca2+ stores are depleted by inhibitors of SERCA (sarcoplasmic/endoplasmic
      reticulum Ca2+-ATPase). Previous studies found that Ca2+-store depletion does not
      produce a CIF (Ca2+ influx factor) activity in 401L cells. These observations
      have prompted the question whether 401L cells possess the signalling machinery
      that permits non-voltage-gated Ca2+ influx to occur. We tested the hypothesis
      that ryanodine-sensitive Ca2+ pools and activation of RyRs (ryanodine receptors)
      constitute a signalling pathway capable of inducing Ca2+ influx in 401L cells. We
      found that 401L cells express mRNA for RyR1 and RyR2 and that RyR activators
      induced Ca2+ release. Activation of RyRs robustly couples with Ca2+ influx
      responses in 401L cells, in sharp contrast with absence of Ca2+ influx when cells
      are treated with SERCA inhibitors. Thus it is clear that 401L cells, despite
      lacking depletion-induced Ca2+ influx pathways, express the functional components
      of a Ca2+ influx pathway under the control of RyR function. These findings
      further support the importance of the 401L cell line as an important cell
      phenotype for deciphering Ca2+ influx regulation.

PMID- 15482259
TI  - Calcium-induced tertiary structure modifications of endo-beta-1,3-glucanase from
      Pyrococcus furiosus in 7.9 M guanidinium chloride.
AB  - The family 16 endo-beta-1,3 glucanase from the extremophilic archaeon Pyrococcus
      furiosus is a laminarinase, which in 7.9 M GdmCl (guanidinium chloride) maintains
      a significant amount of tertiary structure without any change of secondary
      structure. The addition of calcium to the enzyme in 7.9 M GdmCl causes
      significant changes to the near-UV CD and fluorescence spectra, suggesting a
      notable increase in the tertiary structure which leads to a state comparable, but
      not identical, to the native state. The capability to interact with calcium in
      7.9 M GdmCl with a consistent recovery of native tertiary structure is a unique
      property of this extremely stable endo-beta-1,3 glucanase. The effect of calcium
      on the thermodynamic parameters relative to the GdmCl-induced equilibrium
      unfolding has been analysed by CD and fluorescence spectroscopy. The interaction
      of calcium with the native form of the enzyme is studied by Fourier-transform
      infrared spectroscopy in the absorption region of carboxylate groups and by
      titration in the presence of a chromophoric chelator. A homology-based model of
      the enzyme is generated and used to predict the putative binding site(s) for
      calcium and the structural interactions potentially responsible for the unusual
      stability of this protein, in comparison with other family 16 glycoside
      hydrolases.

PMID- 15482262
TI  - Coeliac disease: against the grain.

PMID- 15482260
TI  - Linkage and linkage disequilibrium analysis of the lipoprotein lipase gene with
      lipid profiles in Chinese hypertensive families.
AB  - Elevated TG [triacylglycerol (triglyceride)] is a significant independent risk
      factor for cardiovascular disease. LPL (lipoprotein lipase) is one of the key
      enzymes in the metabolism of the TG-rich lipoproteins which hydrolyses TG from
      the chylomicrons and very-LDL (low-density lipoprotein). To investigate the
      relationship between the LPL gene and lipid profiles, especially TG, in 148
      hypertensive families, we have chosen seven flanking microsatellite markers and
      four internal markers of the LPL gene and conducted linkage analysis by SOLAR and
      S.A.G.E. (statistical analysis for genetic epidemiology)/SIBPAL 2 programs, and
      linkage disequilibrium analysis by QTDT (quantitative transmission/disequilibrium
      test) and GOLD (graphical overview of linkage disequilibrium). There were
      statistically significant differences in lipid levels between subjects without
      and with hypertension within families. A maximum LOD score of 1.3 with TG at the
      marker D8S261 was observed by SOLAR. Using S.A.G.E./SIBPAL 2, we identified a
      linkage with TG at the marker 'ATTT' located within intron 6 of the LPL gene
      (P=0.0095). Two SNPs (single nucleotide polymorphisms), HindIII and HinfI, were
      found in linkage disequilibrium with LDL-cholesterol levels (P=0.0178 and
      P=0.0088 respectively). A strong linkage disequilibrium was observed between the
      HindIII in intron 8 and HinfI in the exon 9 (P<0.00001, D'=0.895). Linkage
      disequilibrium was also found between the 'ATTT' polymorphism in intron 6 and two
      SNPs (P=0.0021 and D'=0.611 for HindIII; and P=0.00004, D'=0.459 for HinfI). The
      present study in the Chinese families with hypertension suggested that the LPL
      gene might influence lipid levels, especially TG metabolism. Replication studies
      both in Chinese and other populations are warranted to confirm these results.

PMID- 15482264
TI  - Receiving a hepatitis C-positive diagnosis.
AB  - BACKGROUND: There is a paucity of academic literature that describes patients'
      experiences of receiving a hepatitis C-positive diagnosis, doctors' explanations
      of the infection and referral to support services. AIM: The aim of the present
      study was to report findings on receiving a positive diagnosis from a study of
      people with hepatitis C infection. METHOD: A cross-sectional study of people with
      hepatitis C infection living in New South Wales, Australia, was carried out
      (n=504). RESULTS: Of participants diagnosed with hepatitis C infection from 1989
      to 2001 (n= 17), just under one-third (29.5%, n=123) reported that they had
      received 'no explanation' about their infection from their doctor at diagnosis.
      Women and those diagnosed from 1989 to 1996 were significantly more likely to
      report receiving no explanation than men and those diagnosed later (35.4 vs 23.7%
      and 37.5 vs 23.0%, respectively). Similarly, current injecting drug users and
      those diagnosed from 1989 to 1996 were significantly more likely to report
      receiving no post-test counselling than those who were not currently injecting
      and those diagnosed later (42.9 vs 30.2% and 37.6 vs 25.9%, respectively).
      Participants diagnosed from 1997 to 2001 were significantly more likely to report
      receiving pamphlets about hepatitis C infection (39.2 vs 23.7%), information
      about treatments (24.5 vs 16.2%) and advice regarding natural therapies (9.1 vs
      3.8%) than those diagnosed earlier. CONCLUSIONS: These data provide evidence of
      an increase in the dissemination of hepatitis C information by doctors at
      diagnosis during the late 1990s. Continued effort is needed to improve doctors'
      provision of information and referral to specialists and support agencies for
      people newly diagnosed with hepatitis C.

PMID- 15482265
TI  - Would general practitioners support a population-based colorectal cancer
      screening programme of faecal-occult blood testing?
AB  - BACKGROUND: The success of a population-based screening for colorectal cancer
      (CRC) is determined to a large extent by general practitioner (GP) attitudes,
      beliefs and support. The extent to which GPs support population-based CRC
      screening remains unclear. AIMS: To assess the knowledge, attitudes and practices
      of GPs in relation to CRC screening, and to identify the determinants of GP
      support for population-based faecal-occult blood testing (FOBT). METHODS: A cross
      sectional postal survey was conducted with a random sample of 692 GPs in
      Queensland, -Australia. We assessed GP knowledge, attitudes and practices
      concerning CRC screening in relation to their stance on population-based FOBT
      screening. RESULTS: Although the response rate was low (41%), participants were
      representative of Queensland GPs in general. Of 284 participating GPs, 143
      (50.5%) indicated that they would support a population-based FOBT screening
      programme, 42 (14.8%) would not and 98 (34.6%) were unsure. Belief in FOBT test
      efficacy (P <0.001), possession of CRC guidelines (P <0.05) and belief in earlier
      stage detection (P <0.05) were major determinants of support for population-based
      FOBT screening. No significant association was observed for doctor's sex,
      location of practice, age, year completed medical training, membership of a
      Division of General Practice, number of weekly consultations, number of patients
      investigated for CRC per month, size of practice, own family history of CRC,
      interest in further information on CRC screening or treatment, and current use of
      FOBT with asymptomatic patients aged > or =40 years. CONCLUSIONS: GP support for
      FOBT population-based screening appears to have increased over recent years. The
      knowledge and attitudes/beliefs of GPs are key determinants of their support.

PMID- 15482266
TI  - Telopeptides as markers of bone turnover in rheumatoid arthritis and
      osteoarthritis.
AB  - AIMS: The aim of the present study was to determine if urinary excretion of type
      I collagen N-terminal telopeptides (UrNTx) and deoxypyridinoline (UrDPD) and
      serum levels of type I collagen C-terminal telopeptides (SeCTx) differed in
      patients with rheumatoid arthritis (RA) compared with populations matched for age
      and gender with and without osteoarthritis (OA). The correlation of markers of
      bone turnover with disease activity in patients with RA or radiographic severity
      in patients with OA was also examined. METHODS: Patients with RA aged >50 years
      (men) and >60 years (women) were identified from computer databases at two
      tertiary referral centres for rheumatology. Strict exclusion criteria were
      applied to avoid the effects of factors known to influence markers of bone
      turnover. Patients with RA and OA were matched for age and sex with a control
      population free of known arthritic disease and a population with OA. Bone markers
      were assayed in serum and urine. Urine markers were measured on three consecutive
      days and mean values used to minimize day-to-day variability of these analytes.
      RESULTS: The level of UrNTx was elevated in patients with RA compared with normal
      controls and patients with OA. UrNTx and UrDPD correlated with markers of disease
      activity in patients with RA (erythrocyte -sedimentation rate and C-reactive
      protein), but not with -clinical signs of inflammation (swollen and tender joint
      counts). Patients with OA failed to show any correlation between markers of bone
      turnover and radiographic severity. CONCLUSIONS: These data support a role for
      the use of UrNTx and UrDPD in further studies of the patho-physiology of RA and
      in longitudinal studies designed to modify the course of clinical disease.

PMID- 15482267
TI  - Towards evidence-based use of serum tumour marker requests: an audit of use in a
      tertiary hospital.
AB  - BACKGROUND: Serum tumour markers (TM) are often measured in hospital patients.
      The reasons for their use and their benefits with regards to earlier cancer
      diagnosis and patient management are not known. AIMS: To identify the patterns of
      TM use in a tertiary hospital and to determine the usefulness and appropriateness
      of requests in this setting. METHODS: A cross-sectional, retrospective study of
      TM ordered over a 3-month period was conducted. Data were obtained from patient
      records. CA-125, CA 15-3, CA 19-9, carcinoembryonic antigen (CEA), and alpha
      fetoprotein (AFP) were studied. Prostate specific antigen was not separately
      investigated. The reasons for ordering, usefulness and appropriateness of use
      were defined prior to analysis. RESULTS: A total of 476 TM was ordered in 373
      patients. One hundred and six (22%) of all results were abnormal by laboratory
      criteria. AFP was the most popular test ordered. Forty-seven per cent of patients
      had no cancer diagnosis. Oncological units (ONC) ordered 27% of tests. The most
      popular reasons for TM ordering were for screening (36%) followed by diagnostic
      aid (19%). ONC units ordered TM mainly for monitoring disease status, as opposed
      to non-ONC units who ordered TM usually for diagnostic aid. TM were deemed
      appropriately ordered in 69% of cases. Twenty-nine per cent of TM were helpful in
      patient management. Only four results (<1%) aided in diagnosis. CONCLUSIONS: The
      reasons and appropriateness of TM use varied depending on the specialization of
      the requesting clinician. The current serum TM are most useful as aids in cancer
      patients, rather than for diagnosis (P <0.0001). Apart from AFP, these TM seem to
      have limited use in the general medical, non-oncological patients. Guidelines for
      their use in this setting are needed.

PMID- 15482268
TI  - Prognostic implication of ST-segment resolution following primary percutaneous
      transluminal coronary angioplasty for ST-elevation acute myocardial infarction.
AB  - BACKGROUND: ST-segment changes have been shown to correlate with myocardial
      tissue perfusion. Complete ST-segment resolution after thrombolysis in acute
      myocardial infarction is associated with lower mortality and better left
      ventricular function. Primary percutaneous transluminal coronary angioplasty
      (PTCA) for acute myocardial infarction restores better epicardial coronary flow
      to the infarct-related artery than thrombolysis. However, ST changes may persist
      and flow can remain poor despite a patent vessel. AIM: To examine the prognostic
      implication of ST-segment resolution immediately following primary and rescue
      PTCA for ST-elevation acute myocardial infarction (STEMI). METHODS: Records of
      201 consecutive primary and rescue PTCA performed at Westmead Hospital for STEMI
      from January 2000 to December 2001 were reviewed. ST-segment elevation (taken 20
      ms after the end of the QRS complex) was measured immediately before and after
      the procedure. ST-segment resolution of greater than 70% after the procedure was
      considered as -'complete' ST-segment resolution, whereas ST-segment resolution of
      less than 70% was considered as 'incomplete' ST-segment resolution. RESULTS: Of
      the 201 patients, 117 (58%) had complete ST-elevation resolution and 84 (42%) did
      not. There was a significant difference in survival free of major adverse
      cardiovascular events; 60% of those with complete ST-segment resolution were
      event-free at 2 years compared with 35% of those patients without complete ST
      segment resolution. CONCLUSION: ST-segment resolution after primary and rescue
      PTCA for STEMI is associated with significantly higher event-free survival. The
      goal of primary angio-plasty should be the restoration of normal epicardial flow
      with normalization of ST-segments.

PMID- 15482269
TI  - Assessment and management of falls in older people.
AB  - Falls remain a major cause of mortality and morbidity for older Australians,
      despite considerable growth in falls prevention activity in recent years. Risk
      factors for falls are well defined, and there is a growing evidence base from
      randomized controlled trials in community settings indicating a range of
      effective individual and multiple strategy interventions to reduce falls and
      falls injuries. These range from health promotion approaches, such as group
      exercise programmes, through to multidisciplinary, multifactorial interventions
      for high-risk populations. Practitioners need to utilize a range of strategies to
      enhance uptake and sustained participation in falls prevention activities. Future
      research needs to address important gaps, such as compliance issues, and
      interventions for people with cognitive impairment, dizziness and vision loss.
      Further research is also required in residential care and hospital settings,
      where there is relatively little research evidence to guide practice.

PMID- 15482270
TI  - Molecular medicine: a clinician's primer on microarrays.

PMID- 15482271
TI  - Etanercept treatment of renal amyloidosis complicating rheumatoid arthritis.
AB  - Rheumatoid arthritis and juvenile arthritis represent the commonest diseases
      complicated by AA amyloidosis in developed countries. Up to 5% of patients with
      rheumatoid arthritis will develop AA amyloidosis, with renal failure being the
      commonest cause of mortality. To date, treatment of this condition has focused on
      suppressing the underlying inflammatory condition with drugs such as
      cyclophosphamide and chlorambucil, but both these drugs are associated with
      myelotoxicity, leukaemia and sterility. Tumour necrosis factor-alpha (TNF-alpha)
      is thought to be involved in amyloid deposition. The efficacy of anti-TNF-alpha
      therapy (etanercept) in the treatment of renal amyloidosis complicating
      rheumatoid arthritis is demonstrated here and the current scientific data on this
      subject are presented.

PMID- 15482272
TI  - Hyperprolactinaemia associated with a complex cystic pituitary mass: medical
      versus surgical therapy.
AB  - A 39-year-old woman presented with visual loss and hyperprolactinaemia. Magnetic
      resonance imaging showed an intrasellar and suprasellar mass with a large cystic
      component that was hyperintense on T2-weighted imaging. Prolactin levels were up
      to 5400 mIU/L. Following trans-sphenoidal surgery, histology showed -elements of
      both a Rathke's cleft cyst and prolactinoma. We suggest primary surgical
      management of large cystic pituitary lesions with associated hyperprolactinaemia,
      particularly when there is hyperintensity on T2-weighted imaging.

PMID- 15482273
TI  - Assessment of early paraprotein response to vincristine-doxorubicin-dexamethasone
      chemotherapy may help guide therapy in multiple myeloma.
AB  - Vincristine, doxorubicin and dexamethasone (VAD) are commonly used as the initial
      chemotherapy in myeloma patients prior to high-dose therapy and autologous stem
      cell transplantation. We reviewed monoclonal protein responses and survival of 62
      patients treated in this way. Among patients with IgG paraprotein, achievement of
      at least 50% reduction in paraprotein after the first cycle of VAD correlated
      with significantly better event-free survival at 3 years, compared with those
      having less than 50% response. We postulate that early paraprotein response may
      be used to identify high risk patients.

PMID- 15482274
TI  - Is honesty always the best policy? Ethical aspects of truth telling.
AB  - Physicians have not always believed that patients should be told of their
      diagnosis. Modern, western medical practice places a high value on providing
      accurate, truthful information to patients. This is heavily influenced by the
      commitment to patient autonomy and participation in decision-making. However,
      situations arise where truth telling is difficult to achieve, creating a dilemma
      for the treating doctor. This article discusses aspects of truth telling in a
      multicultural society.

PMID- 15482275
TI  - Images in Medicine. Dural venous sinus thrombosis.

PMID- 15482276
TI  - Acute respiratory failure associated with cladribine pneumonitis.

PMID- 15482277
TI  - Antifungal guidelines.

PMID- 15482278
TI  - Highly active antiretroviral therapy.

PMID- 15482279
TI  - Antifungal guidelines.

PMID- 15482280
TI  - Antifungal guidelines.

PMID- 15482282
TI  - Antifungal guidelines.

PMID- 15482283
TI  - Genetic testing: a round table conversation.

PMID- 15482288
TI  - Vitamin and trace metal levels in recessive dystrophic epidermolysis bullosa.
AB  - BACKGROUND: In recessive dystrophic epidermolysis bullosa (RDEB), a good
      nutritional balance is necessary to obtain healing of the chronic wounds.
      However, involvement of the oral mucosa and oesophagus stenosis may be
      responsible for severe nutritional deficiencies. OBJECTIVE: In order to propose
      an adapted nutritional management, we studied the vitamin and trace metal status
      of 14 RDEB patients. METHODS: Height and weight were measured. Plasma levels of
      albumin, iron, ferritin, calcium, parathyroid hormone (PTH), folates, vitamins C,
      D, B12, A, E, B1, B6, PP and B2, zinc, selenium, carnitine and copper were
      measured. RESULTS: Most patients had a significant growth retardation. We found
      iron, vitamin D, C, B6, PP, zinc and selenium deficiencies in 36-70% of the
      patients, without clinical expression, except in one case. Vitamin B1, 12, B2,
      A/RBP, E/lipids and carnitine were normal. The three patients with gastrostomy
      feeding had better growth but still a protein deficiency and sometimes vitamin C,
      B6, PP, zinc and carnitine deficiencies. CONCLUSION: Vitamin and trace metal
      deficiencies are frequent in RDEB, even in patients receiving gastrostomy
      feeding, and often go unrecognized. Regular nutritional evaluation is necessary.
      Dietary advice and supplements should be given. Enteral feeding by gastrostomy
      should be discussed in early childhood.

PMID- 15482289
TI  - Update on detection, morphology and fragility in pili annulati in three kindreds.
AB  - BACKGROUND: Pili annulati is an inherited hair shaft abnormality with a wide
      range of clinical expression. OBJECTIVE: We have examined closely three kindreds
      to reveal levels and character of expression of the phenotype and supplement
      current literature on the threshold for detection and aspects of hair shaft
      fragility. PATIENTS AND METHODS: Eleven cases of pili annulati from three
      families were included in a clinical and morphological study. All cases were
      assessed clinically and by light and scanning electron microscopy (SEM) of hair
      shafts. In addition, transmission electron microscopy (TEM) (four patients) and
      amino acid analysis (three patients) were undertaken on clinically overt cases.
      Results Examination by light microscopy with a fluid mountant was more sensitive
      than clinical examination, increasing the detection rate by 120%. Microscopic
      examination revealed that the characteristic periodic bands become less frequent
      distally in the hair shaft. Microscopic features of weathering were found in two
      cases, adding pili annulati to the list of structural hair shaft dystrophies that
      may weaken hair and dispose to weathering. Amino acid analysis of the hair of
      three patients with pili annulati showed elevated lysine and decreased cystine
      content compared to 12 normal controls, consistent with the reduced threshold for
      weathering. CONCLUSION: Careful light microscopy with fluid-mounted hair is
      needed to detect subjects mildly affected by pili annulati. Expression of the
      phenotype varies widely between individuals, between hairs and within hairs of
      the same individual, where ageing of the hair diminishes detectable features.

PMID- 15482290
TI  - Clinico-epidemiological features of congenital nonbullous ichthyosiform
      erythroderma in the eastern province of Saudi Arabia.
AB  - BACKGROUND: A total of 10 455 new dermatology patients were seen in the
      dermatology clinics of King Fahd Hospital of the University (KFHU), Al-Khobar,
      Eastern Saudi Arabia, between January 1990 and December 1995. We identified 21
      patients with a histopathologically confirmed diagnosis of congenital nonbullous
      ichthyosiform erythroderma (CNBIE). We have reviewed the epidemiological and
      clinical features of these patients. OBJECTIVE: To document the epidemiological
      and clinical features of patients with CNBIE in eastern Saudi Arabia. METHODS: We
      used the dermatology outpatient department (OPD) logbooks to identify diagnosed
      cases of CNBIE from new patients presenting with different dermatological
      problems over a 6-year period. We used specifically designed data-collection
      protocol forms to extract epidemiological and clinical data from the patients'
      medical records. These were entered into a computer database and analysed using
      standard statistical software. RESULTS: A total of 21 patients (five males, 16
      females) with a male : female ratio of 0.31 : 1 were identified from a total of
      10 455 new patients seen in our dermatology clinics over the study period. The
      occurrence rate of CNBIE in our clinics was 0.2%, or two per 1000 new dermatology
      cases. Nineteen (90%) of 21 CNBIE patients were born with collodion membranes.
      Eighty-one per cent of our patients had a positive family history of CNBIE.
      Consanguinity among the parents of our CNBIE patients was significantly high at
      95%. CONCLUSIONS: To the best of our knowledge, this preliminary study is the
      first report of its kind from Saudi Arabia (documenting the clinico
      epidemiological features of CNBIE patients in the Eastern Province). The high
      rate of parental consanguinity among the parents of our Saudi CNBIE patients may
      account for the high incidence rate of this genodermatosis in eastern Saudi
      Arabia. In comparison with results of other studies that reported a low
      occurrence rate of CNBIE among dermatology patients, our results were of a
      significantly higher rate.

PMID- 15482291
TI  - Value of the clinical history for different users of dermoscopy compared with
      results of digital image analysis.
AB  - BACKGROUND: The clinical history of a given pigmented lesion could influence the
      therapeutic decision. Teledermatology and automated image analysis also hold
      great potential for revolutionizing dermatology services. AIM: The aim of this
      retrospective study was to evaluate the diagnostic accuracy of users with
      different experiences in dermoscopy with and without information about patients
      and their history compared with classification by an automated analysing system.
      SETTING: One hundred and fifty-seven dermoscopic images of pigmented lesions,
      taken and proved by histopathology at the Pigmented Lesions Clinic of the
      Department of Dermatology of the University Tuebingen, Germany, were included.
      METHODS: All images were viewed by three investigators with different experience:
      excellent (A), average (B) and beginner (C). In the first dermoscopic
      classification, no information was available. After 3 months the same images were
      once more classified by the three investigators, now with the information about
      the patients and their history. The melanocytic lesions were tested by the
      Tuebinger Mole Analyser. RESULTS: For user A the sensitivity, specificity and
      diagnostic accuracy revealed no improvement on including the history (81.3% to
      84.4%, 94.6% to 92.3% and 92.0% to 90.7%), whereas user B clearly improved his
      results (75.0% to 87.5%, 76.9% to 88.5% and 76.5% to 88.3%). No change in the
      sensitivity was seen by user C (84.4%), but there was a clear improvement in the
      specificity (69.2% to 87.7%) and diagnostic accuracy (72.2% to 87.0%). Using the
      computer algorithm, a sensitivity of 100%, a specificity of 76.9% and a
      diagnostic accuracy of 81.9% were achieved. CONCLUSIONS: The study revealed
      results relevant to the use of dermoscopy: (1) continuing dermoscopic education
      influences the diagnostic accuracy; (2) the history is helpful for averaged users
      and beginners in dermoscopy; (3) digital image analysis has the highest
      sensitivity, but a lower specificity compared to the clinicians; and (4) digital
      dermoscopy could be used for store-and-forward systems in teledermoscopy.

PMID- 15482292
TI  - Sun awareness in Maltese secondary school students.
AB  - BACKGROUND: Studies indicate that reducing exposure to ultraviolet light during
      childhood and adolescence decreases the risk of skin cancer. From a young age,
      children need to be educated about the sun's harmful effects on the skin and how
      best to protect themselves. OBJECTIVE: To help in the design of school-based
      interventions to raise sun awareness, a school survey was carried out to identify
      students' stereotypes and misconceptions. STUDY DESIGN: A total of 965 students
      attending Maltese secondary schools in forms 1, 2 and 3 were surveyed in May
      2002, using a structured questionnaire designed to examine students' sun-related
      attitudes and knowledge. RESULTS: A high level of sun awareness among students
      was demonstrated, with high scores on knowledge of the effects of the sun on the
      skin, knowledge of skin cancer and knowledge of sun protection. Girls were
      clearly more knowledgeable than boys. However, of all the students surveyed, 55%
      thought that a suntan made them look better and 70% thought that their friends
      would desire a tan. These views were commoner among the older students. Skin type
      and hair or eye colour had no bearing on attitudes towards tanning or sun-related
      knowledge. The commonest misconceptions were that 'the sun is bad for your skin
      only when you get sunburnt' and that 'you cannot get too much sun on a cloudy
      day'. Deliberate suntanning was more frequently reported by girls than by boys
      and by students in the higher forms. CONCLUSION: Attitude change lags behind
      knowledge. Future school sun awareness interventions need to take into account
      gender and age differences in students' attitudes and perspectives. They should
      aim at motivating attitude change and preventive behaviour through consistent and
      repeated sun-education messages that are supported by a sun-conscious school
      environment.

PMID- 15482293
TI  - Burning mouth syndrome: the efficacy of lipoic acid on subgroups.
AB  - OBJECTIVE: We have examined the effect of alpha-lipoic acid (ALA, tioctic acid;
      Tiobec), a free radical scavenger, on the discomfort of burning mouth syndrome
      (BMS) in patients who had used tranquillizers previously, compared with those who
      had not. METHODS: In this study we gave lipoic acid for 2 months to two groups of
      20 BMS patients, one of which had previously been treated with tranquillizers.
      RESULTS: The results showed greater effectiveness of lipoic acid in BMS patients
      who had not previously used tranquillizers. CONCLUSIONS: The patients with BMS
      who had previously been treated with tranquillizers responded poorly to therapy
      with lipoic acid compared with those who had not received previous psychotropic
      therapy.

PMID- 15482294
TI  - Photopatch testing: a consensus methodology for Europe.
AB  - A group of interested European Contact Dermatologists/Photobiologists met to
      produce a consensus statement on methodology, test materials and interpretation
      of photopatch testing. While it is recognized that a range of local variables
      operate throughout Europe, the underlying purpose of the work is to act as an
      essential preamble to a Pan European Photopatch Test Study focusing particularly
      on sunscreen chemicals.

PMID- 15482295
TI  - The role of oxidants and antioxidants in generalized vitiligo at tissue level.
AB  - BACKGROUND: The role of oxidative stress has not been fully understood in the
      aetiopathogenesis of vitiligo in different studies. AIM: We aimed to investigate
      the role of the oxidative stress in the pathogenesis of vitiligo. METHODS: In
      this study, we examined levels of superoxide dismutase, glutathione peroxidase,
      malondialdehyde and nitric oxide in tissue of 25 patients with generalized
      vitiligo and 25 healthy controls. RESULTS: Our results revealed that levels of
      superoxide dismutase, glutathione peroxidase and malondialdehyde in tissue were
      significantly increased in patients with generalized vitiligo (P < 0.05).
      However, there was no statistically significantly difference between two groups
      at tissue level of nitric oxide (P > 0.05). CONCLUSION: Our results demonstrate
      the presence of an imbalance in the oxidant-antioxidant system in vitiligo at
      tissue level and provide further support for a free radical-mediated damage as an
      initial pathogenic event in melanocyte degeneration in vitiligo.

PMID- 15482296
TI  - The importance of serum creatine phosphokinase level in the early diagnosis and
      microbiological evaluation of necrotizing fasciitis.
AB  - BACKGROUND: Necrotizing fasciitis (NF) due to group A beta-haemolytic
      streptococci (GAS) is a rare but still life-threatening soft-tissue infection
      characterized by rapidly spreading necrosis of the muscle fascia and of the
      surrounding tissues. NF other than that due to GAS involves the participation of
      one or more anaerobes and/or of non-group A streptococci, Staphylococcus aureus,
      enteric organisms, and may be associated with a better outcome. Early diagnosis
      and treatment, consisting of surgical debridement along with appropriate
      antibiotic therapy, are required to reduce morbidity and mortality rates.
      OBJECTIVES: The aim of the study was to analyse the clinical and laboratory
      findings of patients with GAS NF and with non-GAS NF, and to identify which
      characteristics could help to diagnose NF in the early stages of infection.
      METHODS: We retrospectively analysed the clinical and laboratory findings of 43
      cases of GAS and non-GAS NF that occurred in Belgium (n = 32) and at Saga Medical
      School (Japan) (n = 11) between May 1984 and December 2001. RESULTS: GAS NF more
      frequently occurred in previously healthy individuals than NF due to other
      pathogens (P < 0.05) but was associated with a poorer prognosis. Both for
      patients with GAS NF and with non-GAS NF, the first clinical manifestations often
      suggested a diagnosis of erysipelas or cellulitis and rarely evoked the correct
      diagnosis (12% and 15% of the cases, respectively). However, we found that
      creatine phosphokinase (CPK) values were far higher in patients with GAS NF than
      in those with non-GAS NF. CONCLUSIONS: Our data suggest that GAS may exert
      particular tropism and/or toxicity for muscle, responsible for early muscle
      necrosis. This indicates that elevated levels of CPK in a patient with erysipelas
      or cellulitis-like symptoms should clearly prompt the clinician to exclude the
      diagnosis of GAS NF.

PMID- 15482297
TI  - Lichen amyloidosus treated by hydrocolloid dressings.
AB  - We hereby report a case of lichen amyloidosus in a 69-year-old man unresponsive
      to various treatments. The patient was treated by occlusion with hydrocolloid
      dressings. Considerable subjective and objective improvement was observed with
      respect to the pruritus and cosmetic appearance. We suggest this convenient and
      efficacious treatment as first line therapy.

PMID- 15482298
TI  - Lymphomatoid papulosis associated with parathyroid nodular hyperplasia: report of
      a case.
AB  - The association of cutaneous lymphoproliferative diseases and primary
      hyperparathyroidism (PHP) is infrequent, with only three cases reported to date.
      We present a patient with lymphomatoid papulosis (LyP) who developed
      hypercalcaemia secondary to parathyroid nodular hyperplasia. A review of the
      literature has revealed no similar cases; we therefore believe this to be the
      first description of the association between LyP and PHP.

PMID- 15482299
TI  - Pyoderma gangrenosum with spleen involvement and monoclonal IgA gammopathy.
AB  - A 46-year-old man with a 3-year history of pyoderma gangrenosum was admitted with
      ulceration (6 x 5 cm), on the right leg. Previously he had been treated with
      tapering doses of prednisone (maximum dose 1 mg/kg per day); however, he had had
      a few exacerbations following each taper of prednisone dose.
      Immunoelectrophoresis demonstrated monoclonal IgA gammopathy of lambda light
      chains. Abdominal echography and abdominal computed tomographic scan revealed
      multiple splenic abscesses. Treatment was started with oral prednisone (1 mg/kg
      per day) and cyclosporin (5 mg/kg per day) and 6 weeks later complete remission
      was achieved. Systemic involvement in pyoderma gangrenosum is very rare, and
      according to our knowledge there are only a few cases with spleen involvement.

PMID- 15482300
TI  - Cutaneous sarcoidosis and polycythemia vera.
AB  - Polycythemia vera is classified with myelogenous leukaemia, agnogenic myeloid
      metaplasia and primary thrombocythemia as a myeloproliferative syndrome.
      Cutaneous symptoms have been reported with polycythemia vera, including facial
      plethora, aquagenic pruritus, urticaria, purpura, Sweet's syndrome and pyoderma
      gangrenosum. However, polycythemia vera associated with systemic sarcoidosis has
      been rarely reported. An unusual case of polycythemia vera associated with
      cutaneous sarcoidosis is described.

PMID- 15482301
TI  - Dowling-Degos disease with dyschromatosis universalis hereditaria-like
      pigmentation in a family.
AB  - Dowling-Degos disease is a rare autosomal dominant inherited pigmentary disorder
      characterized by reticulate pigmentation of the flexures, prominent comedone like
      lesions and pitted scars. Dyschromatosis universalis hereditaria is characterized
      by the presence of hypopigmented as well as hyperpigmented macules. We report a
      family showing features of both these diseases.

PMID- 15482302
TI  - Circumscribed juvenile pityriasis rubra pilaris.
AB  - We report the case of a 20-year-old woman with a 10-year history of circumscribed
      juvenile-onset pityriasis rubra pilaris (PRP, type IV). Our patient had well
      defined keratotic follicular papules on an erythematous base located on the
      extensor aspects of the extremities and dorsal aspects of the feet but no
      involvement of the palms and soles. Although most cases of type IV PRP follow a
      favourable course with spontaneous resolution of the lesions, this case
      demonstrates that circumscribed juvenile PRP can be more persistent and lasts
      several years.

PMID- 15482303
TI  - Alopecia neoplastica due to metastatic breast carcinoma vs. extramammary Paget's
      disease: mimicry in epidermotropic carcinoma.
AB  - Clinically similar skin diseases can exhibit phenotypic mimicry as demonstrated
      here for alopecia neoplastica. An 89-year-old female patient had been treated for
      scalp eczema for several years until biopsy revealed pagetoid carcinoma. Her
      clinical history showed a mastectomy 20 years ago. For that reason the
      differential diagnosis was extramammary Paget's disease or epidermotropic
      metastasis of the breast carcinoma. Immunohistochemistry revealed positivity of
      MUC1, indicating that the latter is the case.

PMID- 15482304
TI  - Kaposi's varicelliform eruption in an HIV-positive patient after laser
      resurfacing.
AB  - Kaposi's varicelliform eruption (KVE) is an infection produced by the cutaneous
      dissemination of herpes virus type 1 or 2. Usually this disease has been
      described in atopic patients. In this report we present an HIV-positive woman
      with a Kaposi's varicelliform eruption that started after skin resurfacing with a
      laser. This is the first report, to the best of our knowledge, of Kaposi's
      varicelliform eruption after laser resurfacing. The immunodepressed status of the
      patient may have played a role in her infection.

PMID- 15482305
TI  - A case of subcutaneous panniculitis-like T-cell lymphoma with haemophagocytosis
      developing secondary to chemotherapy.
AB  - A 45-year-old woman presented with fever, generalized skin lesions and multiple
      lymphadenopathies. In her past history she had had six courses of
      cyclophosphamide and cisplatin combination chemotherapy 7 years ago because of an
      ovarian carcinoma. We found pancytopenia in the peripheral blood examination.
      Skin biopsy showed diffuse subcutaneous infiltration reminiscent of panniculitis
      but composed of malignant lymphoid cells that were of T lineage. Bone marrow
      biopsy showed normocellular myeloid tissue with abundant haemophagocytic
      macrophages. Subcutaneous panniculitis-like T-cell lymphoma with haemophagocytic
      syndrome was diagnosed. This is the first case reported of subcutaneous
      panniculitis-like lymphoma occurring secondary to chemotherapy.

PMID- 15482306
TI  - Neutrophilic dermatosis of the dorsal hands in a farmer.
AB  - Neutrophilic dermatosis of the dorsal hands is a recently described disorder,
      which is similar to Sweet's syndrome. It is characterized by erythematous
      plaques, pustules and haemorrhagic bullae located solely on the dorsal surface of
      the hands. We describe a 57-year-old man with neutrophilic dermatosis of the
      dorsal hands that occurred following exposure to a chemical fertilizer. There are
      few cases reported in the literature regarding neutrophilic dermatosis and the
      aetiology remains unclear. For the present case, we propose that neutrophilic
      dermatosis of the dorsal hands might have been induced by the chemical
      fertilizer.

PMID- 15482307
TI  - Oral isotretinoin and haemophilia A.
AB  - The effects of oral isotretinoin on the coagulation system are still not well
      known: some case reports describe thrombocytopenia or thrombocytosis, others
      present different effects on fibrinolysis. We report a case of severe acne
      treated with oral isotretinoin in a patient affected with haemophilia A. In this
      case, which differs from the only other case reported in the literature, oral
      isotretinoin did not appear to influence the haemophilic patient's need of factor
      VIII.

PMID- 15482308
TI  - Linear IgA dermatosis in an immunosuppressed patient after allogenic bone marrow
      transplantation.
AB  - Linear IgA dermatosis (LAD) is a well-recognized acquired subepidermal bullous
      autoimmune disease. LAD is characterized by clinical, histopathological and
      immunopathological findings. We report the case of a 38-year-old man who suffered
      from a chronic myeloic leukaemia. Although he received immunosuppressive therapy
      he developed LAD after an allogenic bone marrow transplantation. After diagnosis
      of LAD was established we started a successful systemic therapy with dapsone,
      while continuing the preliminary medication. Here we report for the first time on
      a possible relationship between LAD and bone marrow transplantation in an
      immunosuppressed patient.

PMID- 15482309
TI  - Linear naevoid psoriasis along lines of Blaschko.
AB  - Congenital linear naevoid psoriasis along Blaschko's lines on the thigh of a 3
      year-old girl is reported. The history of asymptomatic, erythematous scaly
      lesions since birth, the peculiar distribution and the histopathology confirmed
      the diagnosis.

PMID- 15482310
TI  - Hyperkeratotic nail discoid lupus erythematosus evolving towards systemic lupus
      erythematosus: therapeutic difficulties.
AB  - Nail changes occur in about 25% of systemic lupus erythematosus (SLE) cases.
      Onycholysis has been reported as the most frequent abnormality in SLE. Nailbed
      hyperkeratosis may be observed in both SLE and discoid lupus erythematosus (DLE).
      Involvement of the nail apparatus in DLE is extremely uncommon and never
      restricted to it. We report on a patient in whom the clinical features on the
      proximal nailfold were similar to those observed on the skin of a patient with
      typical DLE. This has, to the best of our knowledge, not yet been reported. The
      patient also exhibited a very distinctive prominent subungual hyperkeratosis.
      Interestingly, the patient developed biological alterations suggesting a
      systematization of the disease. Only a combination of systemic corticoids,
      retinoids and antimalarials was able to achieve nail improvement and this partial
      resistance to therapy may be explained by the very unusual subungual
      hyperkeratosis.

PMID- 15482311
TI  - Paraneoplastic vasculitis associated with multiple myeloma.
AB  - The association between vasculitis and cancer has been widely reviewed in recent
      decades. The existence of malignancies in patients with vasculitis has been
      estimated at about 4.5-8%, haematological neoplasms being the most frequently
      observed. The haematological malignancies most frequently described are
      lymphoproliferative diseases such as hairy cell leukaemia and lymphomas. On the
      contrary, the incidence of paraneoplastic vasculitis in patients with myeloma is
      low; up to now, we have found nine cases reported on this subject. We report the
      case of a 73-year-old woman who in 1 year showed three outbreaks of acutely
      painful, purpuric and ulceronecrotic lesions, localized on the lower extremities.
      Histopathological study demonstrated thrombosis in the arterioles and
      leucocytoclastic vasculitis. Complementary tests revealed the presence of
      multiple myeloma.

PMID- 15482312
TI  - Androgen receptor status in lesional and normal skin of patients with rosacea.

PMID- 15482313
TI  - Painful geographic tongue (benign migratory glossitis) in a child.

PMID- 15482314
TI  - Avidity of antibodies to human herpesvirus 7 suggests primary infection in young
      adults with pityriasis rosea.

PMID- 15482315
TI  - Areolar and periareolar pityriasis versicolor.

PMID- 15482316
TI  - Treatment of vitiligo with topical imiquimod.

PMID- 15482317
TI  - Psoriasis of the glans penis in a child successfully treated with Elidel
      (pimecrolimus) cream.

PMID- 15482318
TI  - 'Pityriasis rosea-like' adverse reaction to lisinopril.

PMID- 15482319
TI  - A case of Sweet's syndrome and pemphigus vulgaris.

PMID- 15482320
TI  - Prophylactic short-term use of cyclosporin in refractory polymorphic light
      eruption.

PMID- 15482324
TI  - Elevated serum levels of a c-erbB-2 oncogene product in oral squamous cell
      carcinoma patients.
AB  - OBJECTIVES: Amplification of the proto-oncogene c-erbB-2 (HER-2/neu) has been
      shown to be a prognostic marker in many kinds of cancer including oral squamous
      cell carcinoma (OSCC). In order to obtain further information on the c-erbB-2
      gene product p185, it is necessary to quantify expression levels. In this study
      we used an enzyme-linked immunosorbent assay (ELISA) for the extracellular domain
      of p185 to determine whether a soluble oncoprotein fragment can be detected in
      the serum of OSCC patients. METHOD: Sera from 84 OSCC patients, 51 breast cancer
      patients (as positive controls), and 15 healthy controls were assayed in an
      ELISA. To study c-erbB-2 overexpression in OSCC, and breast cancer tissue samples
      we used an immunohistochemical technique. RESULTS: The mean serum value (ng/ml,
      mean/SD) for the normal controls was 8.46/1.29. We chose the 95% level of normal
      controls as a cut-off to distinguish individuals with elevated levels. The breast
      cancer patients' and OSCC patients' serum values were 13.83/6.82 and 13.1/4.56,
      respectively. Significant differences (P < 0.0001) were observed between normal
      control and OSCC, normal control and the breast cancer group.
      Immunohistochemically detectable p185 (intermediate to high) was noted in 30 of
      61 OSCC, and 24 of 51 breast cancer patients. There was a trend of association of
      serum oncoprotein fragment levels with tumor stages, but not with tumor sizes,
      nodal stages, metastases, and oral habits including betel quid chewing, alcohol
      drinking and smoking in the OSCC group. CONCLUSION: The results of the present
      study raise the possibility that soluble c-erbB-2 protein levels in serum is a
      useful parameter for monitoring the disease status as well as the effect of
      therapy on patients with OSCC.

PMID- 15482325
TI  - The expression of the c-erbB-2 receptor protein in glandular salivary secretions.
AB  - BACKGROUND: As the maintenance medium of the oral cavity, saliva is secreted from
      exocrine glands that include the parotid, submandibular, sublingual, and minor
      salivary glands. Considering that saliva is a fluid suffused with protein, it is
      possible that the solubilized by-products of oncogenic expression may be present
      in saliva. Recent studies suggest the presence of solubilized extracellular
      domain portion of the c-erbB-2 protein in serum, nipple aspirates, and saliva. As
      a consequence, the purpose of this study was to determine the presence and
      concentration of c-erbB-2 in major salivary gland secretions. METHODS: Fifteen
      healthy women had serum, stimulated whole (SWS), parotid (SP), and
      submandibular/sublingual (SS) salivary secretions collected. The specimens were
      analyzed for c-erbB-2 using enzyme linked immunosorbent assays (ELISAs). Western
      blots using c-erbB-2 were also performed on these specimens. RESULTS: The ELISAs
      revealed the presence of c-erbB-2 in SWS (24.50 Units/ml), SP (19.66 Units/ml),
      SS (15.59 Units/ml) and serum (1472.15 Units/ml). Western blots confirmed the
      presence of these 185 kDa proteins. CONCLUSIONS: These results suggest that the
      protein, c-erbB-2, is present in relatively equal amounts in both SP and SS
      glandular secretions. Elevated glandular salivary c-erbB-2 concentrations could
      be useful as a preliminary, non-invasive test in clinical decision making when
      diagnosing salivary gland carcinomas. Additionally, this marker may have utility
      in distinguishing between oral lesions that are benign, pre-malignant and
      malignant in the oral cavity. Further research is required to determine if these
      findings have clinical utility.

PMID- 15482326
TI  - Role of angiogenic and non-angiogenic mechanisms in oral squamous cell carcinoma:
      correlation with histologic differentiation and tumor progression.
AB  - BACKGROUND: Angiogenesis has been demonstrated to associate with various measures
      of tumor aggressiveness in many human malignancies. However, studies of tumor
      angiogenesis in oral squamous cell carcinoma (SCC) are still unclear. Recent
      studies indicate non-angiogenesis mechanism (tumor-lined vessel) may exist in
      certain tumors. Therefore, we investigate microvessel density (MVD) and tumor
      lined vessel in oral SCC. METHODS: Peritumoral and intratumoral MVD were measured
      by immunohistochemical staining. Tumor-lined vessels were identified by double
      staining. Statistical analysis of peritumoral and intratumoral MVD and presence
      of tumor-lined vessels with clinicopathologic parameters was performed. RESULTS:
      The results showed peritumoral MVD increased with disease progression and further
      increases of intratumoral MVD was detected by CD31 and CD34. Non-angiogenesis,
      tumor-lined vessel, presented in oral SCC and correlated significantly with tumor
      size, stage, and histologic differentiation. CONCLUSION: Our results suggest at
      the initiation of oral SCC, increasing vascularity is observed at the periphery
      of the tumor. As the tumor continues to grow, further increases of intratumoral
      vascularity and the presence of tumor-lined vessels are associated with cancer
      progression.

PMID- 15482327
TI  - Nimesulide and indomethacin induce apoptosis in head and neck cancer cells.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to inhibit
      the enzyme cyclooxygenase (COX). There are two isoforms of the enzyme. Recent
      investigations indicate that both isoforms, COX-1 and COX-2, are involved in
      carcinogenesis. METHODS: We investigated the effects of nimesulide, a COX-2
      selective and indomethacin, a non-selective NSAID on the head and neck squamous
      cell carcinoma (HNSCC) cell lines SCC-9 and SCC-25. Effects on cell numbers and
      apoptosis were assayed by cell counting, immunofluorescence and fluorescence
      activated cell sorting (FACS). COX expression was examined by Western blotting.
      RESULTS: The investigated cell lines express COX-1 and COX-2. Nimesulide and
      indomethacin induce apoptosis and cause a reduction of cell number. Incubation
      with NSAIDs upregulated COX-2 expression. CONCLUSION: The results of our study on
      HNSCC cells together with data from different studies showing anti-cancer
      activity of NSAIDs suggest that COX inhibitors could play a role in HNSCC
      treatment and prevention.

PMID- 15482328
TI  - Increased expression of cyclooxygenase (COX)-2 in DMBA-induced hamster cheek
      pouch carcinogenesis and chemopreventive effect of a selective COX-2 inhibitor
      celecoxib.
AB  - BACKGROUND: In recent years, overexpression of cyclooxygenase (COX)-2 protein and
      mRNA has been reported in various cancer tissues. Therefore, it has been
      suggested that COX-2 is related to carcinogenesis. METHODS: Hamsters were treated
      by painting a buccal pouch with a 0.5% DMBA solution dissolved in acetone. Basal
      diet or diets containing 150, 500 and 1500 ppm of celecoxib, a selective COX-2
      inhibitor, were given ad libitum to hamsters, and tumor development was observed.
      RESULTS: Immunohistochemical and Western blot analyses revealed that COX-2
      expression was increased toward the carcinogenesis. Although all hamsters
      developed squamous cell carcinoma, the onset of tumor formation was delayed in a
      dose-dependent manner. Also, tumor growth was retarded and survived animals were
      increased in the group of celecoxib treatment. Histologically, administration of
      celecoxib increased the apoptotic cells in the tumor parenchyma and significantly
      inhibited the angiogenesis in the stroma. CONCLUSIONS: The COX-2 expression was
      increased during hamster cheek pouch chemical carcinogenesis. Administration of
      celecoxib demonstrated the chemopreventive potential against the carcinogenesis.

PMID- 15482329
TI  - Retinoic acid disintegrated desmosomes and hemidesmosomes in stratified oral
      keratinocytes.
AB  - BACKGROUND: Although it is known that retinoic acid (RA) regulates the cellular
      differentiation of skin keratinocytes, the effects of RA on the anchoring
      junction have not been clarified. The effects of all-trans RA on cell-cell and
      cell-matrix connections of gingival epithelial (GE)1 cells in a multilayered
      culture were investigated. METHODS: Ultrastructures of GE1 cells were observed
      and immunohistochemistry was used to detect keratin 4, keratin 13, and desmoglein
      expression. Reverse transcription-polymerase chain reaction was performed to
      detect expression of desmosome and hemidesmosome-associating adhesion molecules,
      keratin 13, and keratin14. RESULTS: Retinoic acid caused immunohistochemical
      diminution of keratin 4, keratin 13, and desmoglein. Ultrastructurally, RA
      induced drastic loss of typical desmosomes and complete loss of hemidesmosomes.
      RA significantly decreased the transcript levels of keratin 13, keratin 14,
      desmoglein 1, and desmocollin 1 in a dose-dependent manner. The 230-kD bullous
      pemphigoid antigen (BPAG1) gene expression was also reduced by RA, whereas
      transcript levels of integrin alpha6, integrin beta4, the 180-kD bullous
      pemphigoid antigen (BPAG2), and laminin 5 were not affected. CONCLUSION: These
      results indicated that RA disintegrated not only desmosomes by depriving the
      cells of desmoglein 1, desmocollin 1, keratin 13, and keratin 4, but also
      hemidesmosomes by reducing the expression of BPAG1 and keratin 14 in basal
      keratinocytes.

PMID- 15482330
TI  - Interleukin-1beta increases RANTES gene expression and production in synovial
      fibroblasts from human temporomandibular joint.
AB  - BACKGROUND: Synovial fibroblasts of temporomandibular joint (TMJ) are poorly
      characterized, although they have important roles in progression of
      temporomandibular disorders (TMD). In this study, we investigated responses of
      synovial fibroblasts to interleukin (IL)-1beta. METHODS: We examined gene
      expression profiles of synovial fibroblasts in response to IL-1beta, using
      Affymetrix GeneChip. Regulated upon activation normal T-cell expressed and
      secreted (RANTES) gene expression was confirmed by polymerase chain reaction
      (PCR) and real-time PCR. RANTES protein levels were measured by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: The RANTES was preferentially up-regulated
      in synovial fibroblasts by IL-1beta. The increase in RANTES gene expression in
      response to IL-1beta was confirmed by PCR and real-time PCR. Protein level of
      RANTES in synovial fibroblasts was also increased by IL-1beta. CONCLUSIONS: The
      RANTES, a cc-type chemokine, has chemotactic effects on lymphocytes and
      monocytes. Increased gene expression and protein production of RANTES in synovial
      fibroblasts, in response to IL-1beta, may play an important role in recruitment
      of inflammatory cells into synovium and progression of synovitis in TMD.

PMID- 15482331
TI  - Aplasia of submandibular salivary glands associated with ectodermal dysplasia.
AB  - We describe a 28-year-old white Caucasian man displaying many of the physical
      signs of ectodermal dysplasia (ED). An unusual finding was his presentation with
      xerostomia. Salivary gland imaging techniques revealed aplasia of both
      submandibular salivary glands and relatively small parotids. The case highlights
      that hypoplasia and aplasia of exocrine glands could be rare features of ED. In
      the management of ED, early detection of xerostomia is important to limit any
      potential damage to the already hypodontic dentition.

PMID- 15482332
TI  - Lichen sclerosus et atrophicus of the oral mucosa.
AB  - Lichen sclerosus et atrophicus (LSA) is a chronic, benign, depigmenting disease
      of the skin and mucous membranes most frequently affecting the female genitalia.
      Involvement of the oral mucosa without concurrent genital or skin lesions has
      been reported only occasionally in the literature. In view of the rarity of
      reported cases, one lesion affecting only the labial mucocutaneous area is
      presented along with a description of the disease's clinical and
      histopathological findings.

PMID- 15482333
TI  - Hepatopulmonary syndrome.
AB  - The hepatopulmonary syndrom occurs when pulmonary microvacular dilatation causes
      hypoxemia in cirrhosis. It is found in between 15-20% of patients with chronic
      liver diseases and should be considered in the differential diagnosis of dyspnea
      or abnormal arterial oxygenation in this group. The presence of HPS appears to
      significantly increase mortality in affected patients with cirrhosis. The
      mediators of intrapulmonary vasodilatation and HPS are not fully characterized
      although pulmonary nitric oxide overproduction appears to be a key event in human
      and experimental models. Contrast echocardiography is the best screening test for
      pulmonary vasodilatation. Currently there are no effective medical therapies for
      HPS, although liver transplantation results in reversal of HPS in most cases.
      However, mortality is higher in patients with HPS undergoing transplantation
      relative to those without HPS.

PMID- 15482334
TI  - Calcineurin inhibition and disease recurrence in the hepatitis C virus-positive
      liver transplant recipient.
AB  - Development of hepatitis C virus (HCV)-related disease following liver
      transplantation is more aggressive than in non-transplant individuals, and
      accounts for approximately 10% of liver allograft failures. HCV disease
      progression appears to have accelerated in recent years, possibly due to the
      aging donor population and/or changing immunosuppression regimens, and survival
      among HCV-negative patients is falling. Various risk factors have been proposed
      for HCV disease recurrence, but choice of calcineurin inhibitor is one of the few
      that can potentially be modified by the physician. Cyclosporine (CsA) has been
      shown in vitro to suppress HCV replication as effectively as interferon alpha
      (IFN-alpha), an effect that is separate from the immunosuppressive activity of
      CsA. Data from bone marrow patients and non-transplant patient populations
      confirm that CsA inhibits HCV replication. This anti-HCV effect is not seen with
      tacrolimus. Histologically, there is evidence that progression of fibrosis in HCV
      positive liver transplant patients may be slower with CsA than tacrolimus. The
      clinical implications of the anti-HCV effect of CsA require evaluation versus
      tacrolimus in a large-scale multicenter study.

PMID- 15482335
TI  - Psychoneurological symptoms during interferon therapy in patients with chronic
      hepatitis: prospective study on predictive use of Cornell Medical Index and
      electroencephalogram.
AB  - BACKGROUND/AIMS: We assessed the usefulness of the Cornell Medical Index (CMI)
      and electroencephalogram (EEG) in the prediction and early detection of
      psychoneurological symptoms associated with interferon (IFN) therapy for chronic
      viral hepatitis. METHODS: Forty-eight consecutive patients received IFN for
      chronic viral hepatitis for 8-24 weeks. CMI was measured before IFN therapy.
      Serial EEGs were recorded before IFN therapy, 2, 4 weeks, and thereafter every 4
      weeks in the therapy. RESULTS: Psychoneurological symptoms including insomnia,
      depression, and restlessness were seen in 11 (23%) of 48 patients. Five (13%) of
      40 patients with CMI I and II and six (75%) of eight with CMI III developed
      psychoneurological symptoms (P<0.001). Sensitivity, specificity, and predictive
      accuracy of CMI III were 55%, 95%, and 75%, respectively. Abnormal EEG such as
      slow basic rhythm, appeared in 13 patients (27%) during IFN therapy.
      Psychoneurological symptoms were seen in six (46%) of the 13 patients with
      abnormal EEG, and in five (14%) of 35 in whom EEG remained normal (P<0.05).
      CONCLUSIONS: CMI is useful for the prediction of IFN-induced psychoneurological
      symptoms in patients with chronic viral hepatitis. Serial EEGs contribute to the
      screening and auxiliarily assessing the adverse effects of IFN on the central
      nervous system.

PMID- 15482336
TI  - Lymphocyte T helper-specific reactivity in sustained responders to interferon and
      ribavirin with negativation (seroreversion) of anti-hepatitis C virus.
AB  - BACKGROUND: Seroreversion, negativation of anti-hepatitis C virus previously
      positive, is sometimes found in some chronic hepatitis C-sustained responders
      (SRs) to antiviral therapy. AIMS: To determine the probability of seroreversion
      in SR treatment with Interferon and Ribavirin, and lymphocyte T helper (CD4+)
      reactivity to HCV antigens. METHODS: Thirty SR were followed on average for 54.8
      months. Anti-HCV was tested by third generation test. Peripheral blood
      mononuclear cells (PBMCs) were isolated from venous blood and cultured to
      evaluate CD4+ proliferation in response to 2 microg/ml of eight HCV recombinant
      antigens from core, NS3, NS4, NS5 regions. RESULTS: Seroreversion was verified in
      23% of patients (7/30), appearing at 47.5+/-24.0 months. The probability of anti
      HCV loss in this group was 25% at 56 months after ending therapy. In 57% (4/7),
      anti-HCV returned to positive. These 7 SR patients with seroreversion also showed
      weaker CD4+ reactivity in 5% of tests (3/56) than the remaining 23 anti-HCV
      positive SRs who showed stronger reactivity in 18% of tests (33/184), P=0.036.
      CONCLUSIONS: One-quarter of the SR showed seroreversion of anti-HCV and weaker
      CD4+ specific HCV proliferation than those who remained anti-HCV positive. The
      data suggest that complete viral eradication is a possible and achievable
      clinical objective.

PMID- 15482337
TI  - The role of transcatheter arterial embolization in patients with resectable
      hepatocellular carcinoma: a nation-wide, multicenter study.
AB  - PURPOSE: The role of transcatheter arterial embolization (TAE) for patients with
      resectable hepatocellular carcinoma (HCC) is controversial. Analyzing a cohort of
      nation-wide data can delineate the beneficial effect of TAE for those patients.
      METHODS: From 1991 to 1995, 818 patients who had potentially resectable HCC from
      four medical centers in Taiwan were enrolled. Among them, 599 underwent curative
      resection, 157 received TAE and 62 received supportive treatment alone. The
      survivals among the three groups were compared. RESULTS: The 5-year survival
      rates for patients who underwent surgery, TAE and supportive treatment were
      43.6%, 25.6% and 3.7%, respectively. Surgery offered the best survival for those
      patients. TAE could also prolong survival as compared with supportive treatment
      (P=0.0001). However, among patients who were in advanced tumor stage (Cancer and
      the Liver Italian Program (CLIP) score > or =2), no statistical difference in
      survival was noted between patients who underwent TAE or supportive treatment. In
      multivariate analysis, single tumor, serum albumin > or =3.5 g/dl, tumor size
      less than 5 cm, early-stage tumor (CLIP score=0-1) and aggressive treatment
      including surgery and TAE were independent factors associated with a better
      survival. CONCLUSIONS: Surgery is superior to TAE for patients with resectable
      HCC. In patients who refuse surgery, TAE can be considered for selected patients
      whose tumors are in early stage.

PMID- 15482338
TI  - Assessment of tumor hemodynamics in small hepatocellular carcinoma: comparison of
      Doppler ultrasonography, angiography-assisted computed tomography, and
      pathological findings.
AB  - AIM: We evaluated the usefulness of Doppler ultrasonography (DUS) for the
      analysis of tumor hemodynamics in small hepatocellular carcinoma (HCC). METHODS:
      We compared Doppler ultrasound (DUS) findings with angiography-assisted computed
      tomography (Angio-CT) such as CT during arterial portography and during hepatic
      arteriography in the evaluation of the intratumoral hemodynamics, and with
      pathologic findings in 45 small HCC nodules (< or =3.0 cm in diameter) of 43
      patients. DUS flow pattern of each nodule was categorized into three types:
      afferent continuous flow (Type 1), afferent pulsatile flow with afferent
      continuous flow (Type 2), and afferent pulsatile flow without afferent continuous
      flow (Type 3). Intratumoral blood supply was determined by Angio-CT, and
      pathologic findings were evaluated on resected or biopsied specimen. RESULTS:
      Based on Angio-CT findings, Type 1 nodules showed decreased arterial blood supply
      (ABS) without decreased portal blood supply (PBS). Type 2 nodules showed
      unchanged ABS but decreased PBS. Type 3 nodules showed both increased ABS and
      decreased PBS. DUS findings well represented blood supply of HCC evaluated by
      Angio-CT. In addition, all Type 1 and 2 nodules were well-differentiated HCC, and
      all Type 3 nodules were moderately or poorly differentiated HCC; DUS findings
      well reflected differentiation of HCC. CONCLUSIONS: DUS is a non-invasive imaging
      method and can be used for the evaluation of the stage of malignancy of small
      HCC.

PMID- 15482339
TI  - Overexpression of extracellular signal-regulated protein kinase and its
      correlation with proliferation in human hepatocellular carcinoma.
AB  - BACKGROUND: Dysregulation of cell proliferation is one of the most important
      features of human cancers including hepatocellular carcinoma (HCC). However, the
      molecular basis underlying the proliferation of HCC has not been fully clarified.
      Because a previous study reported that overexpression of extracellular signal
      regulated protein kinase (ERK), which transduces extracellular growth stimuli to
      the nuclei, was frequently observed in several human cancers, this study was
      performed to analyze the expression of ERK in human HCC and its correlation with
      HCC proliferation. METHODS: Twenty-four paired samples of primary HCCs and
      corresponding noncancerous liver tissues, and six samples of histologically
      normal liver tissue were obtained from surgically resected materials. The
      expression of ERK was examined by immunoblotting and immunohistochemical
      analysis. Proliferative activity of each HCC was examined by immunohistochemical
      demonstration of proliferative cell nuclear antigen (PCNA). RESULTS: The ERK1 and
      ERK2 expression in HCCs was significantly higher than that in noncancerous liver
      tissues, and the ERK1 expression in noncancerous liver tissues from patients with
      HCC was higher than that in tissue from normal liver. Immunohistochemical
      examination revealed enhanced accumulation of ERK1 in the nuclei of HCC cells.
      Regression analysis revealed a significant correlation between ERK expression and
      PCNA labeling index in HCC. CONCLUSIONS: Our findings suggest that ERK
      overexpression contributes to the proliferation of HCC.

PMID- 15482340
TI  - Implication of inflammation-related cytokines in the natural history of liver
      cirrhosis.
AB  - BACKGROUND/AIMS: Increased serum concentrations of pro-inflammatory cytokines
      have been detected in patients with liver cirrhosis. However, their role in the
      natural history of cirrhosis and portal hypertension, in the absence of
      infection, and the prognostic significance of inflammation-related cytokines have
      not been reported. Our objective was the analysis of the prognostic value of
      inflammation-related cytokines in cirrhotic patients. PATIENTS AND METHODS: Serum
      concentrations of tumor necrosis factor (TNF-alpha) and its soluble receptors I
      and II and interleukin 6 (IL-6), as well as mean blood pressure, plasma renin
      activity, aldosterone, vasopressin and norepinephrine concentrations were
      determined in 72 cirrhotic patients (Child-Pugh score: A 50%, B 33.3%, C 16.7%),
      without any evidence of infection, and in 25 healthy controls. Patients were
      followed up for a median of 35.9 (range 6-60) months. RESULTS: Increased
      concentrations of soluble TNF receptors were detected in cirrhotic patients when
      compared with healthy controls. TNF receptors and IL-6 concentrations were both
      significantly more elevated in advanced phases of cirrhosis (Child-Pugh score C
      vs B and vs A). Sixteen patients died as a related consequence of liver
      cirrhosis. Multivariant analysis demonstrated that Child-Pugh score, mean blood
      pressure and serum levels of TNF receptor I were associated with mortality.
      CONCLUSIONS: In addition to the classic factors implicated in mortality (Child
      Pugh score and hemodynamic parameters), alterations in inflammation-related
      components are of prognostic significance in cirrhotic patients.

PMID- 15482341
TI  - CD14-positive hepatic monocytes/macrophages increase in hereditary
      hemochromatosis.
AB  - BACKGROUND/AIMS: Iron overload in hereditary hemochromatosis (HH) may result in
      hepatic fibrosis and cirrhosis, primarily due to collagen production by hepatic
      stellate cells that become activated to myofibroblasts. Endotoxin-responsive
      monocytes/macrophages (CD14-positive) are potential sources of profibrogenic
      factors. The aims of this study were to determine (1) whether CD14-positive
      monocytes/macrophages are present in the livers of patients with HH and (2) the
      potential relationship between CD14-positive cells and hepatic fibrosis in HH.
      METHODS: HH was diagnosed using standard clinical, biochemical and genotypic
      parameters. Liver specimens from HH patients and control subjects were
      immunostained for CD14, CD68 and alpha-smooth muscle actin (alpha-SMA) and the
      number of cells expressing these antigens was determined. Fibrosis was assessed
      by routine histological methods. RESULTS: The total number of hepatic CD68
      positive monocytes/macrophages was similar in HH patients and control subjects;
      however, there was a nine-fold increase in the number of CD14-positive
      monocytes/macrophages in HH patients. Control subjects had very low levels of
      hepatic CD14 expression. In HH livers with advanced fibrosis, CD14-positive
      monocytes/macrophages were often associated with fibrous septa containing
      myofibroblasts expressing alpha-SMA. CONCLUSIONS: There was a substantial
      increase in hepatic CD14-positive monocytes/macrophages in HH and, in livers with
      advanced fibrosis, these cells were often associated with fibrous septa and
      septal myofibroblasts. The total number of monocytes/macrophages was similar in
      HH and control livers. In control human liver, Kupffer cells had a very low
      expression of CD14. These findings suggest that CD14-positive
      monocytes/macrophages may contribute to the process of hepatic fibrogenesis in
      HH.

PMID- 15482342
TI  - Incomplete septal cirrhosis: an enigmatic disease.
AB  - Incomplete septal cirrhosis is a form of macronodular cirrhosis characterized by
      fine and incomplete septa, which delimit rudimentary regeneration nodules. Its
      etiopathogeny is uncertain and is associated with various diseases such as
      regenerative nodular hyperplasia, idiopathic portal hypertension, and partial non
      cirrhotic nodular transformation, as well as with progression and regression of
      cirrhosis of any etiology. Few studies are available in the literature describing
      the clinical and biological characteristics of incomplete septal cirrhosis. GOAL:
      The objective of the present descriptive study was to study this entity in the
      city of Salvador, Bahia, Brazil, and to compare the histopathological, biological
      and clinical data obtained with those reported in the specialized literature.
      MATERIALS AND METHODS: We reviewed eight cases of incomplete septal cirrhois of
      varieties etiologies. Hepatitis C, autoimmune hepatitis, alcoholic liver disease
      and criptogenic liver disease were present in our cases. Fibrosis progression as
      well as cirrhosis regression could be identified in these patients. CONCLUSIONS:
      We concluded that Incomplete septal cirrhosis is not a disease itself but it
      could be considered as a stage of progression and regression of liver fibrosis.

PMID- 15482343
TI  - Clinical characteristics and outcome of patients with cirrhosis and refractory
      ascites.
AB  - BACKGROUND: In patients with cirrhosis, refractory ascites is associated with a
      poor prognosis and is an indication for liver transplantation. However, factors
      that determine prognosis remain unclear. AIMS: To investigate the predictive
      factors of prognosis in patients with refractory ascites. METHODS: Seventy-five
      patients with refractory ascites were followed-up for 18+/-13 months (mean+/-SD)
      and survival was analyzed. RESULTS: The 1-year probability of survival was 52%.
      Univariate analyses showed that older patients, hepatocellular carcinoma and
      diabetes, all assessed at entry, were associated with significantly increased
      risk ratios of death. The risk ratio of death was significantly lower in
      abstinent alcoholics than in patients with nonalcoholic cirrhosis. The risk ratio
      of death did not significantly differ between patients with nonalcoholic
      cirrhosis and nonabstinent alcoholics. Child-Pugh score at entry had no
      prognostic value. Multivariate analysis showed that older age, hepatocellular
      carcinoma, diabetes and abstinence were independent prognostic factors.
      CONCLUSIONS: In patients with cirrhosis and refractory ascites, older age,
      hepatocellular carcinoma and diabetes, but not Child-Pugh score at entry, were
      independent predictive factors of poor survival while abstinence was an
      independent predictive factor of good survival. These findings should be taken
      into account when deciding on liver transplantation in patients with refractory
      ascites.

PMID- 15482344
TI  - Can inclusion of serum creatinine values improve the Child-Turcotte-Pugh score
      and challenge the prognostic yield of the model for end-stage liver disease score
      in the short-term prognostic assessment of cirrhotic patients?
AB  - BACKGROUND: The model for end-stage liver disease (MELD) score is a useful tool
      to assess prognosis in critically ill cirrhotic patients. However, its short-term
      prognostic superiority over the traditional Child-Turcotte-Pugh (CTP) score has
      not been definitely confirmed. The creatinine serum level is an important
      predictor of survival in patients with liver cirrhosis. AIMS: To evaluate and
      compare the short-term prognostic accuracy of the CTP, the creatinine-modified
      CTP, and the MELD scores in patients with liver cirrhosis. METHODS: CTP,
      creatinine-modified CTP, and MELD scores were calculated in a cohort of 145
      cirrhotic patients. The creatinine-modified CTP was calculated as follows: we
      assessed the mean creatinine serum level and standard deviation (SD) of the 145
      study patients, then assigned a score of 1 to patients with creatinine serum
      levels < or = to the mean, a score of 2 to patients with creatinine levels
      between the mean and the mean+1 SD, and a score of 3 to patients with creatinine
      levels above the mean+1 SD. The creatinine-modified CTP was then calculated by
      simply adding each patients' creatinine score to their traditional CTP scores. We
      calculated and compared the accuracy (c-index) of the three parameters in
      predicting 3-month survival. RESULTS: The creatinine-modified CTP score showed
      better prognostic accuracy as compared with the traditional CTP (P=0.049).
      However, the MELD score proved to be better at defining patients' prognosis in
      the short-term as compared with both the traditional CTP score (P=0.012) and the
      creatinine-modified CTP (P=0.047). The excellent short-term prognostic accuracy
      of the MELD score was confirmed even when patients with abnormal creatinine serum
      levels were excluded from the analysis (c-index=0.935). CONCLUSIONS: Adding
      creatinine values to the CTP slightly improves the prognostic usefulness of the
      traditional CTP score alone. The MELD score has a short-term prognostic yield
      that is better than what is provided by both the CTP and CTP creatinine-modified
      scores, even in cirrhotic patients who are not critically ill. The positive
      results obtained by using the MELD score were confirmed even after excluding
      patients with impaired renal function.

PMID- 15482345
TI  - Effects of venesections and restricted diet in patients with the insulin
      resistance hepatic iron overload syndrome.
AB  - GOAL: We evaluated the effect of venesections and restricted diet on iron and
      metabolic indices and liver function tests in patients with insulin-resistance
      hepatic iron overload (IR-HIO). MATERIALS AND METHODS: Patients were divided in
      three groups: (a) patients without any therapy who were followed-up for 36+28
      months; (b) patients venesected; and (c) patients on dietary treatment. In each
      group baseline and end-point levels of serum iron and metabolic indices, and
      liver function tests were compared by Student's paired t-test and the
      relationship between serum ferritin and the other variables during treatment was
      evaluated by linear regression analysis. FINDINGS AND CONCLUSIONS: In the follow
      up group, iron and metabolic indices did not change over time. Serum alanine
      aminotransferase, gamma-glutamyl transferase, cholesterol and triglycerides
      significantly decreased after iron depletion. Serum glucose, cholesterol,
      triglyceride, ferritin and liver function tests significantly decreased after
      dietary treatment. Transferrin saturation decreased below 20% during phlebotomy
      treatment in 52% of the patients. In conclusion, our results show that IR-HIO
      patients had relatively low amount of iron overload that seems not to increase
      even after a long follow-up period. Both venesections and diet improved iron,
      metabolic and hepatic indices. Data suggest a relationship between hepatic iron
      overload and insulin resistance, and a role for both iron overload and insulin
      resistance in hepatocellular damage. The behaviour of iron indices during
      venesections suggests an impaired iron release from hepatic cells.

PMID- 15482346
TI  - Circulating endogenous cannabinoid anandamide and portal, systemic and renal
      hemodynamics in cirrhosis.
AB  - BACKGROUND: Endocannabinoids may participate in the homeostasis of arterial
      pressure. Recently, anandamide, the most extensively studied endocannabinoid, has
      been proposed as a key mediator in the peripheral arterial vasodilation of
      cirrhosis. OBJECTIVES: To determine if circulating levels of anandamide are
      related to the extent of the peripheral arterial vasodilation, the severity of
      portal hypertension and the degree of liver and renal dysfunction of patients
      with cirrhosis. METHODS: Plasma levels of anandamide and several systemic, portal
      and renal hemodynamic parameters were determined in 18 patients with cirrhosis
      and eight healthy subjects (control group). RESULTS: Plasma levels of anandamide
      were elevated in patients compared to the control group (P<0.05), nevertheless,
      no differences between patients with ascites and well-compensated patients were
      found. There was no correlation between anandamide concentration and arterial
      pressure, cardiac output and systemic vascular resistance, Child-Pugh's score,
      portal pressure, renal vascular resistance, plasma renin activity or plasma
      aldosterone concentration. CONCLUSIONS: Circulating levels of anandamide are
      increased in cirrhotic patients. However, this elevation was unrelated to the
      extent of arterial vasodilation, the severity of portal hypertension or the
      degree of hepatic and renal dysfunction. Although a local hormonal action cannot
      be excluded, our results do not support a relevant contribution of this system in
      the hemodynamic disturbance of cirrhosis.

PMID- 15482348
TI  - Expression of matrix metalloproteinase-2 and -14 persists during early resolution
      of experimental liver fibrosis and might contribute to fibrolysis.
AB  - BACKGROUND/AIMS: Resolution of liver fibrosis is possible but the identity of the
      matrix metalloproteinases (MMPs) which degrade the accumulated collagens is
      uncertain. We examined MMP-2 and MMP-14 expression in established and resolving
      fibrosis to assess their role in resolution of liver fibrosis. METHODS: MMP and
      tissue inhibitor of metalloproteinase (TIMP)-2 expression in liver extracts was
      examined by ribonuclease protection assay, Western blotting and gelatin
      zymography. MMP activity was examined by (14)C gelatin degradation. RESULTS: In
      human cirrhotic liver, MMP-14 mRNA was increased to 230-330% of normal liver
      expression. Both 63 kDa proenzyme and 60 kDa activated form were present.
      Cirrhotic livers had 270-320% of normal liver expression of MMP-2 protein with 20
      25% being the 62 Da activated form. Protein and mRNA for MMP-2 and MMP-14
      progressively increased during 8 weeks of CCl(4) treatment in rats. Between 3 and
      7 days of resolution from CCl(4) liver fibrosis, MMP-2 and MMP-14 persisted at
      elevated levels. Gelatinolytic activity in liver homogenates peaked at 7 days of
      recovery, being 140% above that in livers at peak fibrosis. CONCLUSIONS:
      Increased expression and activation of MMP-2 and -14 occurs even under conditions
      of elevated TIMPs during liver fibrogenesis. During liver fibrosis resolution, as
      TIMP expression decays, the persistence of MMP-2 and MMP-14 may permit collagen
      degradation.

PMID- 15482347
TI  - The role of midkine and pleiotrophin in liver regeneration.
AB  - BACKGROUND/PURPOSE: We studied roles of two closely related heparin-binding
      growth factors, midkine (MK) and plieotrophin (PTN) in the processes of liver
      regeneration after partial hepatectomy. METHODS: Liver regeneration was
      comparatively analyzed using mice deficient in the MK gene (Mdk), mice deficient
      in the pleiotrophin gene (Ptn) and wild-type mice. RESULTS: Migration of
      neutrophils and macrophages to the liver 1-5 days after partial hepatectomy was
      suppressed in Mdk (-/-) mice. Liver damage as assessed by serum aspartate
      aminotransferase was also less severe in the deficient mice. On the other hand,
      cell growth in the liver was generally suppressed in the deficient mice 3-14 days
      after partial hepatectomy. The weight of the liver 7 and 14 days after partial
      hepatectomy was significantly less in Mdk (-/-) mice than wild-type mice. Very
      similar results were obtained using Ptn (-/-) mice except that a significant
      difference in the repaired liver weight was not observed between Ptn (-/-) mice
      and wild-type mice. CONCLUSIONS: MK and PTN are involved both in the inflammatory
      and reparative processes after partial hepatectomy, and as a whole are beneficial
      for liver regeneration.

PMID- 15482349
TI  - Halofuginone can worsen liver fibrosis in bile duct obstructed rats.
AB  - BACKGROUND/AIMS: Halofuginone (HF) is an antifibrotic agent in rat models of
      liver fibrosis caused by repetitive intoxications. A beneficial effect of HF on a
      biliary type of liver fibrosis has not been proven yet. METHODS: Bile duct
      obstructed rats were given HF from the moment of obstruction onwards and compared
      with no treatment. After 3 weeks, respectively, 6 weeks, aminopyrine breath test
      (ABT) and haemodynamic measurements including of portal pressure were carried
      out. Liver pieces were taken for Sirius red quantitative scoring, as well as for
      semiquantitative determinations of collagen type I and III RNA levels. RESULTS:
      ABT was significantly worse in HF-treated rats as compared with no treatment
      (P=0.02). Haemodynamic data and collagen type I and III determinations were not
      significantly different between groups. Biliary fibrosis scores were
      significantly higher in HF-treated rats as compared with no treatment (P=0.03).
      More Sirius red staining was associated with more proliferation of bile ductules.
      CONCLUSIONS: HF may worsen biliary fibrosis. This contrasts sharply with
      antifibrotic effects in other models of liver fibrosis. Distinctive cellular
      mechanisms in biliary fibrosis may explain this discrepancy. One should be
      cautious for chronic application of HF in man with cholestasis.

PMID- 15482350
TI  - Gut and liver handling of asymmetric and symmetric dimethylarginine in the rat
      under basal conditions and during endotoxemia.
AB  - INTRODUCTION/AIM: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor
      of nitric oxide (NO) synthase enzymes, whereas symmetric dimethylarginine (SDMA)
      competes with arginine transport. Although both dimethylarginines may be
      important regulators of the arginine-NO pathway, their metabolism is largely
      unknown. In previous studies, evidence was found for the liver in the metabolism
      of dimethylarginines. We aimed to investigate dimethylarginine handling of the
      gut and the liver in detail under basal conditions and during endotoxemia.
      METHODS: Twenty-one male Wistar rats were used for this study. Endotoxemia was
      induced by lipopolysaccharide (LPS) infusion (8 mg/kg). Blood flow was measured
      using radiolabeled microspheres according to the reference sample method.
      Concentration of dimethylarginines were measured by high-performance liquid
      chromatography. The combination of arteriovenous concentration difference and
      organ blood flow allowed calculation of net organ fluxes and fractional
      extraction (FE) rates. RESULTS: Arterial plasma concentration of ADMA was lower
      in LPS rats, in contrast to a higher SDMA concentration. For the gut, net release
      of ADMA was found, which was higher in LPS rats. In contrast, for the gut, net
      uptake of SDMA was found, which was lower in LPS rats. For the liver, a high net
      uptake of ADMA was found in both groups, while FE was significantly increased in
      LPS rats. Hepatic handling of SDMA was negligible. CONCLUSION: The liver plays an
      important role in eliminating ADMA from the circulation and endotoxemia
      stimulates this capacity. In contrast to the liver, the gut releases ADMA.
      Endotoxemia results in a reduced systemic ADMA concentration.

PMID- 15482351
TI  - Should we advise patients to treat migraine attacks early?

PMID- 15482352
TI  - Benefits of treating highly disabled migraine patients with zolmitriptan while
      pain is mild.
AB  - Clinical trials of migraine therapy often require treatment when migraine pain
      intensity is moderate or severe, but many physicians find this practice
      artificial and patients often prefer to treat while pain is mild. This
      randomized, placebo-controlled study assessed the efficacy of zolmitriptan 2.5 mg
      in treating migraine while pain is mild, in patients who typically experience
      migraine attacks that are initially mild, but progress to moderate or severe. The
      intent-to-treat population comprised 280 patients (138 zolmitriptan; 148
      placebo), with mean MIDAS grades of 29.6 (zolmitriptan) and 27.6 (placebo).
      Zolmitriptan 2.5 mg provided a significantly higher pain-free rate at 2 h (43.4%
      vs. 18.4% placebo; P < 0.0001). Significantly fewer zolmitriptan patients
      reported progression of headache pain to moderate or severe intensity 2 h
      postdose (53.7% vs. 70.4% placebo; P < 0.01), or required further medication
      within 24 h (46.4% vs. 71.1% placebo; P < 0.0001). The efficacy of zolmitriptan
      was more pronounced in patients treating during the first 15 min following pain
      onset. Adverse events were reported in 31.2% of patients treated with
      zolmitriptan (vs. 11.3% for placebo), and the incidence was lower in patients who
      treated early after attack onset. Zolmitriptan provides high efficacy when
      treating migraine while pain is mild, with the clinical benefits being more
      pronounced when treating early after migraine onset.

PMID- 15482354
TI  - Deep brain stimulation for intractable chronic cluster headache: proposals for
      patient selection.
AB  - Cluster headache is the most severe of the primary headaches. Positron emission
      tomography and functional MRI studies have shown that the ipsilateral posterior
      hypothalamus is activated during cluster headache attacks and is structurally
      asymmetric in these patients. These changes are highly specific for the condition
      and suggest that the cluster headache generator may be located in that brain
      area; they further suggest that electrical stimulation of that region might
      produce clinical improvement in chronic cluster headache sufferers refractory to
      medical therapy. In five patients with severe intractable chronic cluster
      headache, hypothalamic electrical stimulation produced complete and long-term
      pain relief with no relevant side-effects. We therefore consider it essential to
      propose criteria for selecting chronic cluster headache patients for hypothalamic
      deep brain stimulation before this procedure is undertaken at other academic
      medical centres.

PMID- 15482353
TI  - Early treatment of a migraine attack while pain is still mild increases the
      efficacy of sumatriptan.
AB  - To investigate the hypothesis that early treatment of a migraine attack with
      sumatriptan, while pain is still mild, results in higher pain free rates in
      comparison to delayed treatment, when pain is at least moderate, we performed a
      prospective, controlled and open label study. Migraineurs with or without aura
      who fulfilled the diagnostic criteria recommended by the International Headache
      Society were enrolled in the study and randomly assigned to either 'early' or
      'late' treatment with sumatriptan 100 mg tablets. In the early treatment group
      significantly more patients were pain free at all times measured during two hours
      after dosing than in the late treatment group. Furthermore, patients in the early
      treatment group became pain free significantly sooner after dosing than patients
      who delayed treatment. It is concluded that migraineurs, who are able to
      differentiate between a migraine attack and other forms of headache, benefit from
      early intervention with sumatriptan 100 mg tablets.

PMID- 15482355
TI  - Selective vs. complete family interview for detecting those affected by familial
      cluster headache.
AB  - This study validates the method of interviewing only the first-degree relatives
      indicated by the proband as possible cluster headache sufferers. We interviewed
      essentially all the first-degree relatives (93%) of 87 probands with cluster
      headache. We found only one new first-degree relative with cluster headache (1/40
      = 2.5%). The selective interview may be used with confidence as a means of
      investigating the hereditary component of cluster headache.

PMID- 15482356
TI  - The place of osmophobia and taste abnormalities in migraine classification: a
      tertiary care study of 1237 patients.
AB  - This study evaluates osmophobia and taste abnormalities in relationship to
      sensitivity and specificity in the classification of migraine. Consecutive
      International Headache Society (IHS) classified patients (n = 1237) were
      evaluated. Symptoms were graded from 0 to 3. Osmophobia and taste abnormalities
      were tested for sensitivity and specificity in migraine diagnosis. The patients
      were 85.4% female and their mean age was 38.1 years. Of 673 patients 24.7%
      complained of osmophobia, and 24.6% of 505 complained of taste abnormalities. In
      the absence of nausea and vomiting the combinations of two symptoms gave the
      following sensitivity and specificity percentages, respectively: photophobia and
      phonophobia, 10.6 and 84.9; photophobia and osmophobia, 1.1 and 99.0; phonophobia
      and osmophobia, 1.1 and 98.6; photophobia and taste abnormality, 9.6 and 99.0;
      phonophobia and taste abnormality, 9.6 and 98.8; and osmophobia and taste
      abnormality, 4.2 and 99.4. Osmophobia and taste abnormalities were demonstrated
      to be very specific in diagnosing migraine IHS 1.1-1.6, but very insensitive.

PMID- 15482357
TI  - Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan
      and ibuprofen in the treatment of migraine attacks.
AB  - Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently
      used in clinical trials in the acute treatment of migraine attacks. Recently the
      efficacy of a new high buffered formulation of 1000 mg effervescent ASA without
      metoclopramide compared to placebo has been shown. To further confirm the
      efficacy of this new formulation in comparison with a triptan and a nonsteroidal
      anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind,
      randomized trial with 312 patients was conducted in Germany, Italy and Spain.
      Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg),
      ibuprofen (400 mg) and placebo. The percentage of patients with reduction in
      headache severity from moderate or severe to mild or no pain (primary endpoint)
      was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for
      placebo. All active treatments were superior to placebo (P < 0.0001), whereas
      active treatments were not statistically different. The number of patients who
      were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with
      ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA
      and sumatriptan was statistically significant (P = 0.025). With respect to other
      secondary efficacy criteria and accompanying symptoms no statistically
      significant differences between ASA and ibuprofen or sumatriptan were found. Drug
      related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients
      treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000
      mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in
      the treatment of migraine attacks regarding headache relief from moderate/severe
      to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most
      effective.

PMID- 15482358
TI  - Clinical features, effectiveness of drug-based treatment, and prognosis of new
      daily persistent headache (NDPH): 30 cases in Japan.
AB  - Although new daily persistent headache (NDPH) is considered to be one of the most
      refractory headaches to pharmacological treatment, the effectiveness of drug
      based treatment, and the prognosis of NDPH have not been well studied. The
      purpose of this study is to evaluate the effectiveness of pharmacological
      treatment of NDPH. Seventeen men and 13 women who met the IHS diagnostic criteria
      for NDPH, were treated for five years from November 1997 to October 2002, and
      whose headache conditions were entirely available for reference as of October
      2003 were investigated in Toyonaka Municipal Hospital. Mean age at onset 35.0
      years (range 13-73 years). The onset of headache occurred in relation to a
      stressful life event in six (20%) patients and any precipitating events could not
      be identified in 24 (80%) patients. For treatment, muscle relaxants were first
      administered and if no effect was observed, tricyclic antidepressants, selective
      serotonin reuptake inhibitors, and antiepleptic drugs were subsequently
      administered. Results of the drug-based treatments in the 30 cases were 'very
      effective' for eight (27%) cases, 'moderately effective' for one (3%) case,
      'mildly effective' for six (20%) cases, and 'not effective' for 15 (50%) cases.
      According to the survey on the phone for the patients who did not improve to the
      level of 'mildly effective' or better and did not come back to our institution as
      of October 2003, there were no cases found to have spontaneously improved to the
      level of 'mildly effective' or better. These results suggest that NDPH is highly
      recalcitrant to the treatments with poor prognosis and better treatments are
      needed.

PMID- 15482359
TI  - Prevalence of migraine in a rural area in South Tanzania: a door-to-door survey.
AB  - We set out to assess the prevalence during the previous year of migraine in a
      rural area surrounding the Mnero Diocesan Hospital in Southern-Tanzania. A door
      to-door survey from August until December 1999 using a questionnaire based on the
      criteria of the International Headache Society (IHS), including 1047 households
      with 3351 persons, was done, consisting of a screening dialogue with a
      representative family member followed by a face-to-face interview with the
      affected subject. Of the 3351 participants (female 1876; male 1475; age > 10
      years), 23.1% had suffered from headache during the past year; overall prevalence
      of migraine was 5.0% (female 7.0%; male 2.6%); 1.4% reported migraine without
      aura (female 1.8%; male 0.9%); and 3.6% reported migraine with aura (female 5.2%,
      male 1.6%). The peak prevalence was found in female persons in the fourth
      (11.1%), in male persons in the third decade of life (3.8%). Compared with other
      African surveys, the prevalence rate of migraine headache in South Tanzania is
      slightly higher than among Ethiopian and Zimbabwean Africans.

PMID- 15482360
TI  - Glyceryl trinitrate may trigger endogenous nitric oxide production in patients
      with chronic tension-type headache.
AB  - Experimental studies in humans have shown that nitric oxide (NO) may play an
      important role in initiation of primary headaches. It has been proposed that
      activation of L-arginine-NO pathway and increased endogenous production of NO may
      be responsible for NO induced headache. NO is synthesized from L-arginine and
      that reaction also yields citrulline. In the present study we aimed to
      investigate plasma levels of citrulline and arginine as markers of NO production
      after infusion of the NO donor, glyceryl trinitrate (GTN). We recruited 16
      patients with chronic tension-type headache and 16 healthy controls. The subjects
      were randomly allocated to receive 0.5 microg/kg/min GTN or placebo over 20 min.
      Patients were examined on headache free days. Blood samples were collected at
      baseline and 60 min after start of infusion. Both patients and controls developed
      stronger immediate headache on the GTN day than on the placebo day (P = 0.008).
      The headache was more pronounced in patients than in controls (P = 0.02). Plasma
      levels of citrulline increased significantly 60 min after start of GTN infusion
      compared to placebo infusion in patients (P = 0.01) but not in controls (P =
      0.50). Plasma levels of arginine were unchanged in both patients (P = 0.12) and
      controls (P = 0.18). We suggest that GTN administration may trigger endogenous
      production of NO in patients with chronic tension-type headache resulting in
      activation of perivascular sensory afferents.

PMID- 15482361
TI  - Cephalic venous congestion aggravates only migraine-type headaches.
AB  - We performed the Queckenstedt's (Q)-test (compression over bilateral internal
      jugular veins) and a sham test on 33 patients with migraine attacks (coded as 1.1
      based on headache classification proposed by International Headache Society
      (IHS)), 15 with migrainous attacks (IHS code 1.7), and 15 with tension-type
      headache (IHS code 2.1) in both supine and sitting positions. 'Migrainous
      headache' (code 1.7) was defined if the headache characteristics fulfilled all
      but one criteria for 'migraine without aura'. Migraine sufferers reported a
      marked increase in headache intensity after a 30-second Q-test in both supine and
      sitting positions. Aggravation was greater in the supine position. The intensity
      increase was not demonstrated in the sham test, or in patients with migrainous
      attacks or tension-type headaches after the Q-test. Patients with acute migraine
      thus appear more sensitive to increased cerebral venous pressure or intracranial
      pressure. The discrepancy of intensity changes between supine and sitting
      positions may reflect different amount of venous return through the internal
      jugular veins.

PMID- 15482362
TI  - Prevalence of primary headaches in people with multiple sclerosis.
AB  - The aim was to investigate the lifetime prevalence of headache and primary
      headache (diagnoses according to International Headache Society criteria) in
      multiple sclerosis (MS). The relationships between headache and clinical features
      of MS and MS therapy were also investigated. We studied 137 patients with
      clinically definite MS; 88 reported headache, 21 of whom developed headache after
      the initiation of interferon. The prevalence of all headaches in the remaining
      116 patients was 57.7%. Migraine was found in 25.0%, tension-type headache in
      31.9%, and cluster headache in one patient. A significant correlation (P = 0.007,
      Fisher's exact test) between migraine and relapsing-remitting MS was found.
      Primary headaches are common in MS patients. Further studies are needed to
      clarify the mechanisms underlying this association, particularly the association
      between migraine and relapsing-remitting MS, and the role of interferon in the
      development of new headache.

PMID- 15482363
TI  - SUNCT syndrome responsive to intravenous lidocaine.
AB  - Short-lasting unilateral neuralgiform headache with conjunctival injection and
      tearing (SUNCT) is a primary headache syndrome that has been reported to be
      resistant to treatment with intravenous lidocaine. We report four cases of SUNCT
      in whom intravenous lidocaine (1.3-3.3 mg kg(-1) h(-1)) completely suppressed the
      headaches for the duration of the infusion. The headache returned after cessation
      of treatment. Two patients went on to have their symptoms controlled on
      topiramate (50-300 mg daily). One patient had typical migrainous aura in
      association with some of the attacks of pain but never migrainous headaches.
      These cases suggest that treatment with lidocaine can be considered when acute
      intervention is required to suppress a severe exacerbation of SUNCT, and further
      broaden the therapeutic and clinical background of this syndrome.

PMID- 15482364
TI  - Gabapentin-responsive idiopathic stabbing headache.
AB  - Idiopathic stabbing headache (ISH) is defined as the occurrence of short-lasting,
      painful jabs, restricted to the ophthalmic division of the trigeminal nerve. It
      is closely related to other forms of headache (such as migraine and tension-type
      headache) and has been reported among all age groups, including children and
      adolescents. As pathogenic mechanisms of the disease remain unclear, management
      decisions are empirical and limited to few options. Classically, indomethacin has
      been considered the first option, but therapeutic failure occurs in up to 35% of
      cases. In this setting, we report four patients with young-onset indomethacin
      resistant ISH which had good responses to gabapentin and discuss the use of this
      drug in the presenting situation.

PMID- 15482365
TI  - Indomethacin-responsive hemicrania associated with an extracranial vascular
      malformation: report of two cases.

PMID- 15482366
TI  - Headache in Sturge-Weber syndrome: a case report and review of the literature.

PMID- 15482367
TI  - Periodic autonomic dysfunction without pain in a patient with cluster headache.

PMID- 15482368
TI  - Hemicrania continua evolving from migraine with aura: clinical evidence of a
      possible correlation between two forms of primary headache.

PMID- 15482369
TI  - In memory of Professor Virgilio Gallai.

PMID- 15482371
TI  - Current guidelines applicable for the approval of topically applied
      dermatological drugs in the EU.
AB  - Dermatologicals as well as other medicinal products are submitted to the rules
      governing medicinal products in the European Union (EU) (Directive 2001/83/EC).
      With appreciation of the EU enlargement those regulatories deserve a recent
      consideration with special regard to the peculiarities of external dermatological
      therapy, recently passed novel and future guidelines. As regards the criteria for
      authorization of a medicinal product it is set out in Regulation (EEC) 2309/93
      Article 11(1) that a marketing authorization shall be refused if it appears that
      the quality, the safety or efficacy of the medicinal product have not been
      adequately or sufficiently demonstrated by the applicant. Article 26(1) of
      Council Directive 2001/83/EC is worded a little differently but the criteria are
      the same irrespective of the procedure for the marketing authorization. For the
      final evaluation of the benefit/risk profile of a topically applied
      dermatological medicinal product not only the active agent but the whole galenic
      formulation as well has to be taken into account as the extent of penetration of
      the active compound might be influenced by changing the non-active substances.
      Furthermore the vehicle itself - independent of the active agent - influence the
      dermatological disorder, often in dependence on the stage of the dermatopathy.
      With special concern to safety/tolerability the (photo)toxic and (photo)allergic
      potential of the dermatological drug have to be taken into consideration too. In
      case of total body therapy in children the differing percutaneous resorption due
      to another body surface/body weight relation deserves special concern. The
      following review gives a survey of the current most important EU-guidelines for
      the evaluation of the benefit/risk profile of topically applied dermatological
      medicinal drugs and an outlook on further developments. As systemically applied
      dermatological medicinal products are assessed like other systemically applied
      drugs they are not treated in the following contribution.

PMID- 15482372
TI  - CDP-choline increases plasma ACTH and potentiates the stimulated release of GH,
      TSH and LH: the cholinergic involvement.
AB  - In the present study, we investigated the effect of intracerebroventricular
      (i.c.v.) administration of cytidine-5'-diphosphate (CDP) choline on plasma
      adrenocorticotropin (ACTH), serum growth hormone (GH), thyroid stimulating
      hormone (TSH), follicle stimulating hormone (FSH) and luteinizing hormone (LH)
      levels in conscious rats. The involvement of cholinergic mechanisms in these
      effects was also determined. In basal conditions, CDP-choline (0.5, 1.0 and 2.0
      micromol, i.c.v.) increased plasma ACTH levels dose- and time-dependently, but it
      did not affect the TSH, GH, FSH and LH levels. In stimulated conditions, i.c.v.
      administration of CDP-choline (1 micromol, i.c.v.) produced an increase in
      clonidine-stimulated GH, thyrotyropin-releasing hormone (TRH)-stimulated TSH, LH
      releasing hormone (LHRH)-stimulated LH, but not FSH levels. Injection of
      equimolar dose of choline (1 micromol, i.c.v.) produced similar effects on
      hormone levels, but cytidine (1 micromol, i.c.v.) failed to alter plasma levels
      of these hormones. Pretreatment with hemicholinium-3, a neuronal high affinity
      choline uptake inhibitor, (20 microg, i.c.v.) completely blocked the observed
      hormone responses to CDP-choline. The increase in plasma ACTH levels induced by
      CDP-choline (1 micromol, i.c.v.) was abolished by pretreatment with mecamylamine,
      a nicotinic receptor antagonist, (50 microg, i.c.v.) but not atropine, a
      muscarinic receptor antagonist, (10 microg, i.c.v.). The increase in stimulated
      levels of serum TSH by CDP-choline (1 micromol, i.c.v.) was blocked by atropine
      but not by mecamylamine pretreatment. However, CDP-choline induced increases in
      serum GH and LH levels were greatly attenuated by both atropine and mecamylamine
      pretreatments. The results show that CDP-choline can increase plasma ACTH and
      produce additional increases in serum levels of TSH, GH and LH stimulated by TRH,
      clonidine and LHRH, respectively. The activation of central cholinergic system,
      mainly through the presynaptic mechanisms, was involved in these effects. Central
      nicotinic receptors solely mediated the increase in plasma ACTH levels while the
      activation of central muscarinic receptors was involved in the increase in TSH
      levels. Both muscarinic and nicotinic receptor activations, separately, mediated
      the increases in serum GH and LH levels after CDP-choline.

PMID- 15482373
TI  - Nigella sativa seed extracts enhance glucose-induced insulin release from rat
      isolated Langerhans islets.
AB  - Nigella sativa L. 'Black cumin' (Ranunculaceae) is one of the plants commonly
      used in Moroccan folk medicine for treatment of various ailments including
      diabetes mellitus. The present study was undertaken to investigate the effect of
      different N. sativa seed extracts on insulin secretion. Different fractions of
      the seed were prepared: the defatted fraction (HR II), which was divided into two
      subfractions: the first (HR III) containing acidic and neutral compounds and the
      second (HR IV) containing basic compounds. The insulin secretory effects of these
      extracts were evaluated individually at different concentrations (0.01, 0.1, 1
      and 5 mg/mL), in vitro in isolated rat pancreatic islets in the presence of 8.3
      mmol/L glucose. The results show that addition of the defatted whole extract or
      of the basic subfraction of the seed in the incubation medium significantly
      increased glucose-induced insulin release from the islets. In the case of the
      acidic and neutral subfraction, the stimulatory effect was observed only for the
      higher concentration (5 mg/mL). However, a clear concentration-dependent increase
      in insulin release from isolated pancreatic islets was observed for the basic
      subfraction. Our data show that the antidiabetic properties of N. sativa seeds
      may be, at least partly, mediated by stimulated insulin release, and that the
      basic subfraction largely contributes to this stimulatory effect. Further
      phytochemical studies are underway in order to isolate the pharmacological
      compound(s) responsible for the insulinotropic effect of N. sativa seeds.

PMID- 15482374
TI  - Volume-sensitive chloride channels (ICl,vol) mediate doxorubicin-induced
      apoptosis through apoptotic volume decrease in cardiomyocytes.
AB  - Apoptosis is associated with early changes in cell volume through a mechanism
      called apoptotic volume decrease (AVD). As volume-sensitive chloride channels
      (I(Cl,vol)) are known to play a key role in the regulation of cell volume, this
      study investigated the role of I(Cl,vol) and AVD in doxorubicin-induced apoptotic
      cell death in adult rabbit ventricular cardiomyocytes. Exposure of cardiomyocytes
      to 1 microm doxorubicin induced a rapid and significant reduction in cell volume
      of cardiomyocytes (average of 15%), i.e. AVD as well as increases in the early
      markers of apoptosis, annexin V labeling and caspase-3 activity. Doxorubicin also
      induced the activation of a current characterized as I(Cl,vol) on the basis of
      the external chloride sensitivity and pharmacological properties with the patch
      clamp technique. Doxorubicin-induced AVD and apoptosis were both abolished when
      cardiomyocytes were exposed to the I(Cl,vol) inhibitors 5-nitro-2-(3
      phenylpropylamino) benzoic acid (NPPB) (0.1 mM) or indanyloxyacetic acid 94 (IAA
      94) (10 microM). The crucial role of I(Cl,vol) during AVD and apoptosis was
      confirmed using C(2)-ceramide, another pro-apoptotic compound. These results
      demonstrate that activation of I(Cl,vol) plays a major role in the mechanism
      leading to cell shrinkage and apoptosis-induced AVD by agents such as doxorubicin
      or C(2)-ceramide in adult cardiomyocytes.

PMID- 15482375
TI  - Antispasmodic effects of the essential oil of Croton nepetaefolius on guinea-pig
      ileum: a myogenic activity.
AB  - The effects of essential oil of Croton nepetaefolius (EOCN) on guinea-pig
      isolated ileum were studied. We previously demonstrated that EOCN induced
      reversible relaxation of ileal tone artificially increased by high [K(+)]
      nutrient solution. This study aimed to elucidate whether these effects were
      caused by indirect, neural, or primarily by myogenic effect. EOCN (40 microg/mL)
      induced a relaxation of basal tone corresponding to approximately 38% of the
      reference contraction (K(+) 60 mM), and was unaltered by 0.5 mM hexamethonium,
      0.5 microM tetrodotoxin, 1 microM indomethacin, and 100 microM L-nitroarginine
      methyl ester (L-NAME). Epinephrine- (100 microM) and EOCN-induced maximal
      relaxation of ileum pre-contracted with 60 mM KCl represented 16.8 +/- 2.3% (n =
      10) and 95.0 +/- 6.4% (n = 6) of KCl-induced contraction, respectively. EOCN (200
      micro/mL) had no effect on the transmembrane resting potential (E(m)) of ileum in
      nutrient solutions with normal (5 mM) and high (80 mM) [K(+)]. EOCN similarly
      inhibited the contractions induced by KCl, acetylcholine (ACh) and histamine
      (IC(50) values of approximately 18, 28 and 21 microg/mL, respectively). EOCN also
      inhibited both the nifedipine-insensitive component of ACh-induced contraction
      and the contraction induced by ACh in Ca(2+)-free solution. EOCN accelerated the
      reversal of a KCl-induced tonic contraction upon withdrawal of Ca(2+) from the
      extracellular medium. Our results suggest that EOCN induces relaxation of guinea
      pig ileum by a direct action on smooth muscle via a mechanism largely independent
      of alterations of E(m) and Ca(2+) influx, possibly at the level of the
      contractile apparatus.

PMID- 15482376
TI  - 17 Beta-estradiol prevents focal cerebral ischemic damages via activation of Akt
      and CREB in association with reduced PTEN phosphorylation in rats.
AB  - This study aimed to assess the signaling pathway of the neuroprotective action of
      estrogen in the cerebral ischemic injury evoked by subjecting rats to 2-h
      occlusion of the middle cerebral artery (MCA) followed by 24-h reperfusion. Rats
      received 17 beta-estradiol (1, 4 and 10 mg/kg, i.p.) 24 h before and 5 min after
      the completion of 2-h MCA occlusion. The cerebral infarct area was consistently
      observed in the cortex and striatum of the left hemisphere. Increased terminal
      deoxynucleotidyl transferase-mediated deoxyuridine-biotin nick-end labeling
      (TUNEL)-positive cells and DNA fragmentation in the penumbral zone were
      significantly reduced by 17 beta-estradiol. In line with these results, 17 beta
      estradiol significantly increased Akt and cyclic AMP response element binding
      protein (CREB) with increased Bcl-2 protein in the ischemic area, whereas the
      elevated the phosphatase and tensin homolog deleted from chromosome10 (PTEN)
      phosphorylation was significantly reduced with decreased Bax protein and
      cytochrome c release. Inhibition of DNA fragmentation, PTEN phosphorylation, and
      Akt activation by 17 beta-estradiol were antagonized by iberiotoxin, a maxi-K
      channel blocker. Taken together, it is suggested that suppression of cerebral
      ischemic injury by 17 beta-estradiol may be ascribed to the maxi-K channel
      opening-coupled downregulation of PTEN phosphorylation and upregulation of Akt
      and CREB phosphorylation with resultant increase in Bcl-2 protein and decrease in
      Bax protein and cytochrome c release.

PMID- 15482377
TI  - Interactions between aspirin and COX-2 inhibitors or NSAIDs in a rat thrombosis
      model.
AB  - Recent in vitro studies, clinical trials and epidemiological studies have
      suggested possible interactions between aspirin and other cyclo-oxygenase (COX)
      inhibitors, such as ibuprofen of the COX-2 inhibitors celecoxib and rofecoxib.
      The objective of this study was to test the effects of aspirin (1, 2.5 and 5
      mg/kg), and ibuprofen (4 and 15 mg/kg), diclofenac (2.5 mg/kg), flurbiprofen (2
      mg/kg), celecoxib (7.5 mg/kg), and rofecoxib (1 mg/kg), alone or combined on a
      rat model of arterial thrombosis. Drugs were given orally daily for 7 days,
      before insertion of an arterio-venous shunt thrombosis system, left in place for
      15 min. Main parameter was thrombus weight. Five to 12 rats were used per
      experiment, and 35 controls overall. Aspirin inhibited thrombus formation in a
      dose-dependent manner. All NSAIDS given alone also inhibited thrombus formation
      to approximately the same level as aspirin 1 mg/kg/day. Ibuprofen, celecoxib and
      rofecoxib inhibited the effects of aspirin, but not diclofenac or flurbiprofen.
      The interactions with aspirin do not seem to affect all NSAIDs to equal levels.
      The clinical impact of this needs to be confirmed in adequately powered clinical
      trials or pharmaco-epidemiological studies.

PMID- 15482378
TI  - Influence of a thiazole derivative on ethanol and thermally oxidized sunflower
      oil-induced oxidative stress.
AB  - The present work describes the protective influence of the dendrodoine analogue
      (DA) [4-amino-5-benzoyl-2-(4-methoxy phenylamino) thiazole] on thermally oxidized
      sunflower oil and ethanol-induced oxidative stress. Ethanol was fed to animals at
      a level of 20% [(7.9 g/kg body weight (bw)] and thermally oxidized sunflower oil
      at a level of 15% (15 mL/100 g feed). Hepatotoxicity was assessed by measuring
      the activity of plasma aspartate transaminase (AST), alkaline phosphatase (ALP)
      and gamma-glutamyl transferase (GGT), which were elevated in thermally oxidized
      oil, and ethanol fed rats when compared with normal control rats. Tissue damage
      was associated with increased lipid peroxidation and disruption in the
      antioxidant defence mechanism in thermally oxidized oil- and ethanol-fed groups
      when compared with normal control group. The activity of liver marker enzymes
      (AST, ALP and GGT) and the level of lipid peroxidation decreased when DA was
      administered along with ethanol and thermally oxidized oil. The antioxidant
      status was near normal in DA-administered groups. Thus we propose that DA exerts
      antioxidant properties by modulating the activity of hepatic marker enzymes,
      level of lipid peroxidation and antioxidant status.

PMID- 15482380
TI  - Fish oils in the care of coronary heart disease patients: a meta-analysis of
      randomized controlled trials.
AB  - What is the place of fish oils in the care of coronary heart disease (CHD)
      patients? As several clinical trials have already addressed this question without
      giving definitive answers, we did a meta-analysis of trials regarding the
      efficacy of omega-3 fatty acids in preventing cardiovascular mortality and
      morbidity. We searched the MEDLINE (1966-2003), EMBASE databases, proceedings
      abstracts and references of reviewed articles. Randomized controlled trials
      (RCTs) of the efficacy of omega-3 fatty acids among adults with recent or acute
      myocardial infarction (MI), or angina were selected. Two reviewers abstracted
      data independently. Five relevant outcomes, mortality from all causes, fatal and
      non-fatal MI, non-fatal stroke and angina, were measured. Data were synthesized
      using a fixed effect model. Ten RCTs with 14,727 patients were included. No
      significant heterogeneity was detected. Daily intake of omega-3 fatty acids for a
      mean duration of 37 months decreased all causes of mortality by 16% (relative
      risk 0.84, 95% confidence interval [0.76; 0.94]) and the incidence of death due
      to MI by 24% (0.76, [0.66; 0.88]). No significant effect was found for the other
      outcomes. Because of the suboptimal quality of the studies included into the meta
      analysis and the absence of data in patients receiving statins, these results do
      not justify adding fish oils systematically to the heavy pharmaceutical
      assortment already recommended in CHD patients.

PMID- 15482379
TI  - Fertility and outcomes of pregnancy after chemotherapy in a sample of
      childbearing aged women.
AB  - The aim of the study was to review the characteristics and outcomes of
      pregnancies occurring in women of childbearing age after chemotherapy for
      malignant disease. Between November 1998 and October 1999, a total of 16 patients
      who were treated for ovary (three), mole (one), vaginal (one), breast (four),
      Hodgkin's disease (four), lung (one), melanoma (one) and osteosarcoma (one)
      carcinoma were identified and retrospectively questioned about their fertility
      status. All the 16 women included in this study received at least one alkylating
      agent. Five patients (31%) experienced anomalies of hormonal cycle during and
      after the treatment. All of them recovered normal cycle without consequence of
      fertility. Caesarean section was performed in seven of 20 (35%) pregnancies with
      known outcomes. No obstetrical events were reported. The 16 women had 21
      pregnancies resulting in 18 normal infants, one newborn with a minor abnormality
      (tallus foot), one spontaneous abortion and one lost of follow-up to 6 months of
      pregnancy. The present survey suggests that cytotoxic drug exposure had no
      deleterious effects on subsequent pregnancies. A prospective and systemic survey
      would be the only means able to clarify the actual cancer therapy on reproductive
      outcome and to investigate the long-term effects in the progeny.

PMID- 15482382
TI  - RNA-mediated gene silencing: mechanisms and its therapeutic applications.
AB  - RNA interference, part of a complicated network of interconnected pathways for
      cellular defence, RNA surveillance and development, has become a powerful tool
      for the experimental manipulation of gene expression. It is the process by which
      double-stranded (dsRNA) silences specific gene expression through homology
      dependent degradation of cognate mRNA. The dsRNA is converted into 21nt small
      interfering RNAs (siRNAs), which directs a complex ribonuclease system to
      substrate mRNA targets. The degradation of the target mRNA is initiated with the
      cleavage at a position corresponding to the centre of the siRNA. Dissecting
      individual cellular pathways to reveal the function of numerous proteins is an
      approach to drug discovery. Interfering RNA (RNAi) serves as a rapid and
      convenient tool, which works in various organisms. RNAi technology has the
      potential to facilitate our understanding of biological processes and potentially
      lead to exciting new drugs. Here we review various experimental approaches
      adopted with RNAi and possible therapeutic applications.

PMID- 15482383
TI  - Quality of life and attitudes towards psychotropics and dependency: consumers vs.
      non-consumers aged 50 and over.
AB  - AIM: To assess the relationships between socio-demographic factors, quality of
      life and attitudes towards psychotropic drugs and dependency and to compare those
      relationships in continuous consumers (CC), occasional consumers (OC) and non
      consumers (NC) of those drugs. METHODS: Quality of life (SF36) and attitudes (14
      statements) were measured in 601 subjects (45-60 years old) from the SUVIMAX
      cohort (SUpplementation en VItamines et en sels Mineraux AntioXydants). Data were
      obtained on 334 NC, 142 CC, 125 OC from the inclusion questionnaire and the
      monthly consumption report notebooks kept by subjects between 1994 and 1998.
      Dichotomous and polychotomous logistic regressions were used for the analysis.
      RESULTS: The lower the quality of life score the more frequent was consumption.
      NC tended to be men, with high quality of life scores. They entertained negative
      attitudes towards psychotropics and dependency. OC tended to be women reporting a
      chronic pathology, with fairly high social status. They had intermediate quality
      of life and denied dependency. CC tended to be men with no professional activity
      and low quality of life scores in particular for mental health and perceived
      health. They had positive attitudes towards psychotropics and accept dependency.
      DISCUSSION: Assessment of patients' quality of life and understanding of their
      attitudes towards psychotropics can provide essential information for those in
      charge of health promotion programmes and may help in identifying new
      intervention strategies. Preventive education and follow-up of therapy may be
      better suited to the needs of patients.

PMID- 15482384
TI  - Beliefs of chronically ill Japanese patients that lead to intentional non
      adherence to medication.
AB  - OBJECTIVE: To identify factors, associated with personal beliefs, involved in
      intentional non-adherence to prescribed medication of Japanese patients with
      chronic diseases. METHODS: A cross-sectional study of Japanese subjects with
      chronic, primarily liver, gastrointestinal, or nervous system diseases who had
      been prescribed oral medicines for regular use, was performed. The subjects were
      admitted to a university hospital and were interviewed face-to-face on admission.
      Intentional non-adherence was defined as experience of deliberate adjustment of
      self-managed prescription medicines during the few months prior to hospital
      admission. Patients' beliefs about taking medicines were assessed from the
      perspective of what the patient valued in order to take medicines without
      anxiety; whether the patient valued information about the medication such as its
      function and side-effects and/or mutual reliance on doctors. Using logistic
      multivariate regression analyses, factors associated with intentional non
      adherence were identified. RESULTS: Among 154 subjects, 51 showed intentional non
      adherence. Intentional non-adherence was associated with the following three
      factors: (a) the patients' beliefs with respect to taking medicines without
      anxiety, especially putting no value on mutual reliance on the patient-doctor
      relationship (P < 0.001) and putting great value on knowing the drug's side
      effects (P < 0.001), (b) poor comprehension of general aspects of medication (P
      for trend < 0.001), and (c) being in the prime of life (40-59 years) (P = 0.011).
      Comprehension of the function of each medicine, experience of side-effects,
      anxiety about taking medicines, and the number of types of medicines taken, were
      not associated with non-adherence. CONCLUSIONS: Beliefs on which individual
      Japanese patients with chronic diseases attach value in order to take medicines
      without anxiety were potential factors for intentional non-adherence. This
      emphasizes the necessity of a patient-oriented approach to take account of
      patients' personal beliefs about medicines to increase adherence rate in Japan.

PMID- 15482385
TI  - Diltiazem use in tacrolimus-treated renal transplant recipients.
AB  - BACKGROUND: Calcium channel blockers are widely used in the treatment of post
      transplant hypertension but have the potential for drug interaction with
      calcineurin inhibitors. Renal allograft outcomes when diltiazem is used with
      cyclosporine have been reported, but similar data with tacrolimus are not
      available. METHODS: We performed a retrospective analysis of all our renal
      transplant recipients from March 1997 to March 2002 who were given tacrolimus,
      mycophenolate mofetil and prednisone. Patients were divided into two groups based
      on whether diltiazem was started in the first postoperative week. Outcome
      measures included renal function up to 2 years post-transplant, blood pressure
      (BP) control, tacrolimus exposure, and costs related to tacrolimus monitoring.
      RESULTS: Sixty-four patients constituted the diltiazem group and 32 the control
      group. Their baseline characteristics were similar. The mean average daily dose
      of diltiazem used was 213.95 mg/day. There was no difference in renal function,
      graft survival, or patient survival over 2 years. BP control was similar although
      the diltiazem group required more medication. Diltiazem was discontinued in four
      patients due to side-effects. There was no difference in tacrolimus-related side
      effects between the two groups. There was also no difference in tacrolimus
      exposure, cost related to tacrolimus monitoring, or combined costs when the
      expense of diltiazem was added. CONCLUSION: Diltiazem use is acceptably safe and
      efficacious in renal transplant recipients treated with tacrolimus-based
      immunosuppressive therapy. It can be considered as a first-line antihypertensive
      in these patients and is cost neutral for tacrolimus use.

PMID- 15482386
TI  - Pamidronate increases bone mineral density in women with postmenopausal or
      steroid-induced osteoporosis.
AB  - INTRODUCTION: We aimed to determine the efficacy and safety of a cyclic
      intravenous therapy with pamidronate in patients with postmenopausal or
      glucocorticoid-induced osteoporosis. METHODS: We enrolled 86 Austrian female
      patients with postmenopausal (n = 69, mean age 68.13 +/- 1.14) or glucocorticoid
      induced (n = 17, mean age 66.89 +/- 2.03) osteoporosis defined as a T-score of < 
      2.5 for bone mineral density (BMD) of the lumbar spine L1-L4. Patients received a
      single intravenous dose of 30 mg pamidronate at 3 months intervals. The per cent
      change in BMD was primary, whereas the safety and the biological response were
      secondary endpoints. RESULTS: Seventy-six female patients (88%) completed study.
      Sixty patients received pamidronate therapy for the treatment of late
      postmenopausal osteoporosis and 16 patients received the same treatment for
      glucocorticoid-induced osteoporosis. At the end of the trial, lumbar spine (L1
      L4) BMD increased significantly in patients with postmenopausal osteoporosis (P =
      0.000067), whereas in patients with glucocorticoid-induced osteoporosis no
      significant change was observed (P = 0.724). The increase in the Ward's triangle
      BMD did not reach significance level in postmenopausal women receiving
      pamidronate (P = 0.0740). However, pamidronate treatment for glucocorticoid
      induced osteoporosis resulted in a significant increase in Ward's triangle BMD (P
      = 0.0029). The efficacy of pamidronate treatment for postmenopausal osteoporosis
      was also reflected in a decrease in circulating biochemical markers for bone
      formation, including alkaline phosphatase and osteocalcin. In addition,
      pamidronate was well tolerated with no incidence of severe gastrointestinal
      events. CONCLUSION: Cyclic intravenous administration of pamidronate is well
      tolerated therapy in postmenopausal osteoporosis, and increases spinal BMD.
      Randomized controlled studies with adequate number of patients are needed to test
      the efficacy of the compound in the treatment of glucocorticoid-induced
      osteoporosis.

PMID- 15482387
TI  - Empiric treatment of uncomplicated UTI in women: wasting money when more is not
      better.
AB  - CONTEXT: Trimethoprim-sulfamethoxazole (TMP-SMX) and nitrofurantoin were until
      recently the two drugs recommended in clinical guidelines in Israel for empiric
      treatment of uncomplicated urinary tract infection (UTI) in women. OBJECTIVES:
      The objective of this study is to evaluate the economic impact of physician non
      adherence to these recommendations. DESIGN SETTING AND PATIENTS: Data were
      derived from the electronic patient records of the Leumit Health Fund. Cases of
      women aged 18 to 75 with a diagnosis of acute cystitis or UTI that were
      empirically treated with antibiotics from January 2001 to June 2002 were
      identified. The final sample comprised 7738 physician-patient encounters. The
      proportion of cases treated with each individual drug was calculated, and the
      excess expenditure because of non-adherence to guidelines from the perspective of
      the Health Maintenance Organization (HMO) was evaluated using 5 days of therapy
      with nitrofurantoin as the reference treatment. RESULTS: TMP-SMX was the most
      frequently prescribed drug (25.81%), followed by nitrofurantoin (14.71%)
      representing a 40.52% rate of adherence to the guidelines. Drugs from the
      fluoroquinolone family were prescribed in 22.82% of cases. Cost of treatment in
      approximately 70% of the cases exceeded the expected cost of the guideline
      therapy. CONCLUSIONS: Suboptimal adherence to the guidelines resulted in a
      significant and avoidable waste of the health plan's resources in both drugs and
      money.

PMID- 15482388
TI  - Isoniazid acetylation phenotyping in Saudi Arabs.
AB  - AIMS: The present study is designed to investigate the acetylator status in Saudi
      Arabs. METHODS: Isoniazid (INH) acetylation phenotyping was studied in 136 Saudi
      Arabs in Riyadh, Saudi Arabia, using a single plasma sample taken 3 h post-INH
      oral dose of 200 mg. Metabolic ratio (MR) of plasma acetyl-INH (Ac-INH) to INH
      was used to determine the acetylation phenotype. RESULTS: The MR had a bimodal
      distribution with an antimode of 1.0. The frequency distribution of slow
      acetylators (MR < 1.0) was 94.9% (n = 129). Using Hardy-Weinberg Law, the gene
      frequency (q) of the recessive allele determining slow acetylator phenotype was
      found to be 0.97. CONCLUSION: INH phenotyping suggests a high frequency of slow
      acetylators among Saudi Arabs. There was no association between the MR of plasma
      Ac-INH/INH and age or gender.

PMID- 15482389
TI  - Do risk factors for lactic acidosis influence dosing of metformin?
AB  - BACKGROUND: Metformin is commonly prescribed to treat type 2 diabetes mellitus,
      however it is associated with the potentially lethal condition of lactic
      acidosis. Prescribing guidelines have been developed to minimize the risk of
      lactic acidosis development, although some suggest they are inappropriate and
      have created confusion amongst prescribers. The aim of this study was to
      investigate whether metformin dose was influenced by the presence of risk factors
      for lactic acidosis. METHODS: The study was prospective, and retrieved
      information from patients admitted to hospital who were prescribed metformin at
      their time of admission. RESULTS: Eighty-three patients were included in the
      study, 60 of whom had a least one risk factor for lactic acidosis. Of those 60
      patients, 78.3% had a dose adjustment, with renal impairment, hepatic impairment,
      surgery and use of radiological contrast media--the risk factors most likely to
      result in a dose adjustment. When dose adjustments did occur, metformin was
      withheld on 88.7% of occasions. CONCLUSION: Metformin dose was influenced by the
      presence of risk factors for lactic acidosis, although it was dependent upon the
      number and particular risk factor/s present.

PMID- 15482390
TI  - Population pharmacokinetic modelling of tramadol with application of the NPEM
      algorithms.
AB  - BACKGROUND AND OBJECTIVE: Although the kinetic behaviour of tramadol has been
      described, the present study is the first to our knowledge, to report
      specifically on the population pharmacokinetic modelling of tramadol
      hydrochloride. METHODS: The parametric Iterative Two-stage Bayesian Population
      Model (IT2B) program followed by the Non-parametric Expectation Maximization
      Population Model (NPEM2) program was used to determine population pharmacokinetic
      parameter values of tramadol in 138 postoperative orthopaedic Malaysian patients.
      All patients had received a 100 mg intravenous dose of tramadol, infused over 2-3
      min, as their first postoperative analgesic. Blood was sampled at 0 min and
      subsequently at 15, 30 min, 1, 2, 4, 8, 16, 20 and 24 h for serum tramadol high
      performance liquid chromatography analysis. RESULTS AND DISCUSSION: The one
      compartmental model pharmacokinetic parameters--volume of distribution (Vd),
      elimination rate constant (kel) and the total clearance rates (ClT)--found were:
      mean Vd = 167.6 +/- 63.84 L; median Vd = 161.48 L; mean kel = 0.1241 +/- 0.056 h(
      1); median kel = 0.1138 h(-1); ClT = 19.57 +/- 9.51 L/h; median ClT =18.12 L/h.
      The interindividual coefficient of variation of ClT (48.56%) was higher than that
      of Vd (38.09%), indicating the presence of other possible influencing factors on
      tramadol's ClT such as CYP2D6 polymorphism, gender and age. Overall, NPEM2
      suggested more diversity in the population than did IT2B.

PMID- 15482391
TI  - Community pharmacy treatment of minor ailments in refugees.
AB  - OBJECTIVE: To evaluate a scheme offering pharmacy referrals for minor ailments in
      a refugee community. To determine if minor ailments could be managed by
      pharmacists offering over-the-counter (OTC) medication, free of charge, to
      refugees exempt from prescription charges. DESIGN: Refugees presenting with minor
      illnesses were offered a voucher. This voucher could be taken to the pharmacist,
      who, after a consultation, could exchange the voucher for appropriate OTC
      medication. SETTING: A refugee community in south London. OUTCOME MEASURES: The
      presenting minor ailment and corresponding medication as recorded by the
      pharmacist. RESULTS: A total of 200 vouchers were distributed to 184 refugees
      over a 5-month period resulting in the dispensing of 264 items. The five most
      frequent minor ailments were: upper respiratory tract infections (37%), headache
      (14%), musculo-skeletal pains (7%), allergy including hay fever (6%), indigestion
      (6%). The five most frequently dispensed items were: paracetamol (28%), sudafed
      (16%), ibuprofen (11%), aspirin (10%) and simple linctus (8%). Only two clients
      were referred directly to the GP and two advised to attend if symptoms persisted.
      CONCLUSIONS: Minor ailment schemes elsewhere have demonstrated the potential to
      divert about one-third of patients with minor illnesses out of general practice
      and to care in the pharmacy. Such a scheme is being widely adopted in Scotland
      this year. Our results are the first to demonstrate the feasibility and
      acceptability of such a scheme in the refugee community.

PMID- 15482392
TI  - Initiation of atypical antipsychotic agents and health outcomes in patients with
      schizophrenia.
AB  - BACKGROUND: Although pharmacological treatments are available for patients with
      schizophrenia, there is a lack of systematic and comprehensive evaluation of
      health outcomes following the initiation of atypical antipsychotic agents.
      OBJECTIVE: To assess the effects of the initiation of olanzapine or risperidone,
      the two most widely prescribed atypical antipsychotics, on patients' health
      outcomes, as measured by changes in patient clinical characteristics between 6
      months prior to and post-initiation. METHOD: We identified patients with
      schizophrenia by >1 inpatient or > or = 2 outpatient ICD-9-CM codes (> or = 7
      days apart) between 1 July 1998 and 30 June 1999, and those who were initiated on
      olanzepine or risperidone during the period 1 April 1999 to 31 March 2000
      inclusive. We then subdivided these patients into three groups: (i) those who
      were not on olanzapine or risperidone, (ii) those who were not on any atypical
      agents, and (iii) those who were not on any antipsychotic agents, for 6 months
      prior to being issued with the new prescription. Using test of means or chi
      square tests, we examined whether the initiation of olanzapine or risperidone is
      related to different changes in patient clinical indicators, such as number of
      drugs for psychiatric conditions, use of psychiatric services, and use of non
      psychiatric services. RESULTS: Between pre- and post-initiation, olanzapine
      initiators had a greater decrease in the number of psychiatric hospitalizations
      and use of psychotropic agents, whereas risperidone initiators had a greater
      reduction in the number of non-psychiatric hospitalizations. The initiation of
      olanzapine and risperidone appear to be associated with different patient health
      outcomes. Compared with olanzapine initiators, risperidone initiators had a
      greater increase in the use of treatments related to mental health, but had
      greater decrease in the use of treatments related to physical health. CONCLUSION:
      Despite olanzapine and risperidone being often perceived as similar antipsychotic
      agents, our results suggest that the clinical outcomes associated with their use
      are different. Outcome data from routine clinical practice are required to
      provide a more comprehensive assessment of these drugs.

PMID- 15482393
TI  - Vardenafil-induced generalized urticaria.
AB  - Vardenafil is a potent selective and reversible inhibitor of the cGMP
      phosphodiesterase type 5 that has been shown to improve erectile function in men.
      Vardenafil is usually well tolerated; the most common adverse events are
      headache, flushing, rhinitis, sinusitis and dyspepsia. We report a case of a 48
      year-old man with an acute episode of widespread urticaria following vardenafil
      consumption and in absence of other identifiable causative factors. The patient
      had no previous episodes of urticaria. This appears to be the first report of
      urticaria associated with vardenafil.

PMID- 15482394
TI  - Unusual hypersensitivity to warfarin in a critically ill patient.
AB  - A patient was admitted to the intensive care unit because of respiratory failure,
      and warfarin therapy was started at 2 mg/day for the treatment of pulmonary
      embolism, together with other medications. Despite the low dosage of warfarin,
      international normalized ratio (INR) was markedly elevated from 1.15 to 11.28 for
      only 4 days, and bleeding symptoms concurrently developed. Vitamin K2 was infused
      along with discontinuation of warfarin. One day later, the INR was found to have
      decreased, and bleeding was also improved. An objective causality assessment
      indicated a probable relationship between clotting abnormality and warfarin
      administration, although the degree of elevation of the INR was unusual in the
      light of the daily warfarin dose and duration of its exposure. Based on the
      clinical status of the patient, it was suspected that several conditions
      contributed to the abnormal hypersensitivity to warfarin. Contributory factors
      probably included pharmacokinetic interactions with co-administrated drugs,
      vitamin K deficiency caused by decreased dietary intake, reduced gut bacterial
      production, impaired intestinal absorption and hepatic synthetic capacity, and
      increased consumption of clotting factors. In view of our experience in the
      present case, it should be stressed that close monitoring of coagulation capacity
      is necessary in critically ill patients in order to avoid fatal haemorrhage after
      initiating warfarin therapy regardless of the dosage.

PMID- 15482395
TI  - Editorial: Community health insurance (CHI) in sub-Saharan Africa: researching
      the context.

PMID- 15482396
TI  - EPI vaccines-induced antibody prevalence in 8-9 year-olds in The Gambia.
AB  - OBJECTIVES: We evaluated antibody prevalence to measles, polio 1 and 3, and
      tetanus toxoid antibodies in 8-9 year-old children in The Gambia within the
      framework of the Gambia Hepatitis Intervention Study (GHIS), a large vaccine
      trial aimed at evaluating vaccine efficacy against hepatitis B virus (HBV)
      infection, chronic carriage and primary liver cancer in a high risk population.
      The results of the present survey were compared with a previous survey performed
      with the same objectives and same methodology but in different children at 3-4
      years of age. METHODS: Four clusters of 200 children each were sampled as
      representative of the whole country. Children would have received BCG, diphtheria
      pertussis-tetanus vaccine (DPT), poliovirus vaccine (OPV), measles and yellow
      fever immunization. The measles haemoagglutination inhibition test (HAI) was used
      to detect measles antibody. Antibodies to polioviruses 1 and 3 were tested using
      the standard polio neutralization assay described in the EPI manual (WHO 1990).
      An enzyme-linked immuno-sorbent assay (ELISA) was used to measure tetanus toxoid
      antibodies. RESULTS: A high proportion of children were fully vaccinated in both
      age groups. Measles antibody concentrations were < or =1 : 8 in 8.2% of 8-9 year
      old vaccinated children. In the previous survey of 3-4 year-old children this was
      11.3%. In the present survey, GMC was lower than in the 3-4 year-old children;
      88% of 3-4 year-olds and 89% of 8-9 year-olds had detectable antibody levels
      against poliovirus type 1. Fewer children at 8-9 years of age had antibodies
      against poliovirus type 3 than 3-4 year-olds (78%vs. 89% P < 0.001). A
      significant overall lower proportion of 8-9 year-old children had detectable
      tetanus toxoid antibodies compared to 3-4 year-old children (87%vs. 95% P <
      0.001), as well as those who received four doses of DPT (90%vs. 97% P < 0.001).
      Conclusions High vaccine coverage is achieved in The Gambia with EPI. With time
      the number of vaccinated children who are not protected against measles,
      poliovirus 3 and tetanus increases. Besides the maintenance of high vaccine
      coverage in infants and young children, booster doses of some of the EPI vaccines
      in adolescents should be considered.

PMID- 15482397
TI  - Impact of malaria control on childhood anaemia in Africa -- a quantitative
      review.
AB  - OBJECTIVE: To review the impact of malaria control on haemoglobin (Hb)
      distributions and anaemia prevalences in children under 5 in malaria-endemic
      Africa. METHODS: Literature review of community-based studies of insecticide
      treated bednets, antimalarial chemoprophylaxis and insecticide residual spraying
      that reported the impact on childhood anaemia. Anaemia outcomes were standardized
      by conversion of packed cell volumes into Hb values assuming a fixed threefold
      difference, and by estimation of anaemia prevalences from mean Hb values by
      applying normal distributions. Determinants of impact were assessed in
      multivariate analysis. RESULTS: Across 29 studies, malaria control increased Hb
      among children by, on average, 0.76 g/dl [95% confidence interval (CI): 0.61
      0.91], from a mean baseline level of 10.5 g/dl, after a mean of 1-2 years of
      intervention. This response corresponded to a relative risk for Hb < 11 g/dl of
      0.73 (95% CI: 0.64-0.81) and for Hb < 8 g/dl of 0.40 (95% CI: 0.25-0.55). The
      anaemia response was positively correlated with the impact on parasitaemia (P =
      0.005, P = 0.008 and P = 0.01 for the three outcome measures), but no
      relationship with the type or duration of malaria intervention was apparent.
      Impact on the prevalence of Hb < 11 g/dl was larger in sites with a higher
      baseline parasite prevalence. Although no age pattern in impact was apparent
      across the studies, some individual trials found larger impacts on anaemia in
      children aged 6-35 months than in older children. CONCLUSION: In malaria-endemic
      Africa, malaria control reduces childhood anaemia. Childhood anaemia may be a
      useful indicator of the burden of malaria and of the progress in malaria control.

PMID- 15482398
TI  - Impact of a double dose of sulphadoxine-pyrimethamine to reduce prevalence of
      pregnancy malaria in southern Mozambique.
AB  - Malarial infection during pregnancy increases the risks of severe sequelae for
      the pregnant woman and the risk of delivering a low birthweight baby. The aim of
      this intervention study was to reduce significantly the prevalence of malaria
      parasitaemia in adolescent parturients in Matola and Boane in Mozambique. The
      study was focused upon the most malaria-vulnerable group, adolescent nulliparous
      and primiparous women. After completing the usual antenatal clinic and giving
      informed consent, 600 pregnant women were randomly chosen in a double blind
      manner to one of two regimens comparing the prevailing routine (placebo) for
      malaria prevention with a two dose regimen of sulphadoxine-pyrimethamine (SP).
      The first dose was given at enrollment with a second dose at the beginning of the
      third trimester. At delivery maternal and placental malaria parasitaemia as well
      as birthweight and gestational duration were analysed. At booking the prevalence
      of malaria parasitaemia was 35.3% in the placebo group and 30.6% in the SP group.
      At the second dose, the prevalence of malaria parasitaemia in the placebo group
      and SP group was 19.7% and 8.7%, respectively. This implies a relative risk (RR)
      of 2.24 with 95% CI (1.34, 3.75). The corresponding figures at delivery were
      13.6% and 6.3% with an RR of 2.22 (1.07, 4.60) and in placenta 13.3% and 2.4%
      with an RR of 4.87 (1.58, 15.0). Newborns with malaria within 7 days were
      significantly more frequent in the placebo group, 6.4% and 0.7% respectively,
      with an RR of 6.55 (1.20, 35.7). Almost all (approximately 98%) of the women
      studied had Plasmodium falciparum, the remainder had P. malariae and P. ovale.
      The mean birthweight in the SP group was 3077 g and in the placebo group 2926 g.
      The estimated mean difference between the two groups was 151 g with 95% CI (51,
      252). The mean placental weight in the placebo group was 596 and 645 g in the SP
      group, implying a difference of 49 g with a 95% CI (11, 88). The mean gestational
      duration was 6.1 days longer in the SP group, 95% CI (1.5, 10.6). In the placebo
      group there were two cases of urticaria and one case of nausea; in the SP group
      there was one case of vomiting. No newborn showed any sign of serious SP side
      effect. Two doses of SP were enough to significantly reduce the prevalence of
      peripheral and placental malaria parasitaemia among young nulliparous and
      primiparous pregnant women in Matola and Boane.

PMID- 15482399
TI  - iNOS promoter variants and severe malaria in Ghanaian children.
AB  - Nitric oxide is an important mediator in the host defence against Plasmodium
      falciparum malaria. It has antiparasitic effects in vitro. However, its role in
      clinical disease remains controversial. Polymorphisms in the inducible nitric
      oxide synthase promoter (iNOS; -954G-->C, -1173C-->T, -2.6 kb CCTTT(n)
      microsatellite) may influence susceptibility to and severity of malaria. We
      tested this hypothesis in a case-control study among Ghanaian children with
      severe malaria (SM) and asymptomatic parasitaemia, respectively, and in healthy
      controls. In this study, the respective frequencies of iNOS-954G-->C and -1173C-
      >T did not differ between groups but > or =13 microsatellite copies were
      associated with SM. -954G-->C and -1173C-->T were in linkage disequilibrium with
      CCTTT(8) and CCTTT(13), respectively. -954G-->C/CCTTT(8) protected against
      hyperparasitaemia whereas -1173C-->T/CCTTT(13) increased fatality. These findings
      suggest that iNOS promoter haplotypes rather than single nucleotide polymorphisms
      are associated with malaria in Ghanaian children.

PMID- 15482400
TI  - Malaria epidemiology in a rural area of the Mekong Delta: a prospective community
      based study.
AB  - Over the past 10 years, the Mekong Delta region in Vietnam has experienced fast
      socio-economic development with subsequent changes in malaria vectors ecology. We
      conducted a 2-year prospective community-based study in a coastal rural area in
      the southern Mekong Delta to re-assess the malaria epidemiological situation and
      the dynamics of transmission. The incidence rate of clinical malaria, established
      on 558 individuals followed for 23 months by active case detection and biannual
      cross-sectional surveys, was 2.6/100 person-years. Over the 2-year study period,
      the parasite rate and malaria seroprevalence (Plasmodium falciparum and P. vivax)
      decreased significantly from 2.4% to almost 0%. Passive case detection (PCD) of
      clinical cases and serological follow-up of newborns carried out in a larger
      population confirmed the low and decreasing trend of malaria transmission. The
      majority of fever cases were seen in the private sector and most were
      unnecessarily treated with antimalarials. Training and involvement of the private
      sector in detection of malaria cases would greatly improve the quality of health
      care and health information system.

PMID- 15482401
TI  - Is amodiaquine failing in Rwanda? Efficacy of amodiaquine alone and combined with
      artesunate in children with uncomplicated malaria.
AB  - We investigated the safety and efficacy of amodiaquine alone (AQ) and combined
      with artesunate (AQ + AS) in 308 Rwandan children 6-59 months old with
      uncomplicated Plasmodium falciparum malaria attending three sentinel sites. The
      two treatment regimes were well tolerated and no serious adverse events were
      recorded. After excluding new infections, children treated with AQ + AS had fewer
      clinical failures at day 28 after treatment than those treated with AQ alone: OR
      = 0.20 [95% CI: 0.06-0.57 (P = 0.001)]. Total (parasitological and clinical)
      failure was also significantly less frequent in the AQ + AS group: OR = 0.34 [95%
      CI: 0.17-0.67 (P = 0.001)]. When adjusting for study site, the hazard ratio for
      treatment failure was 0.37 [95% CI: 0.20-0.68 (P = 0.001)]. Combining AQ with AS
      increases the efficacy of the treatment but the apparent increase of AQ
      resistance observed in just a 1-year period is worrying and casts doubts on the
      suitability of implementing AQ + AS as first-line treatment in Rwanda.
      Alternative treatments should be identified and tested.

PMID- 15482402
TI  - Circulating concentrations of cardiac proteins in complicated and uncomplicated
      Plasmodium falciparum malaria.
AB  - In an unmatched case-control study of 63 non-immune European patients with
      uncomplicated (n = 52) and complicated (n = 11) falciparum malaria, serum levels
      of N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid
      binding protein (H-FABP), myoglobin, troponin T and creatin kinase-muscle brain
      were compared. Elevated levels of NT-proBNP and H-FABP indicated myocardial
      impairment in complicated but not in uncomplicated falciparum malaria. The
      clinical impact of these findings remains to be evaluated. The pathophysiology of
      cardiac impairment in complicated falciparum malaria warrants further
      investigation.

PMID- 15482403
TI  - Antibodies directed against nitrosylated neoepitopes in sera of patients with
      human African trypanosomiasis.
AB  - Antibodies directed against nitrosylated epitopes have been found in sera from
      patients suffering from human African trypanosomiasis (HAT) but not in sera from
      control subjects living in the same endemic area or African control subjects
      living in France. We conjugated amino acids to albumin by glutaraldehyde
      (conjugates) and then nitrosylated the conjugates. Both conjugates and
      nitrosylated conjugates were analysed by enzyme-linked immunosorbent assay
      (ELISA). We detected antibodies directed against nitrosylated L-cysteine and L
      tyrosine conjugates; antibody levels were higher in stage II patients than in
      stage I. Patients with severe clinical signs had higher antibody levels, and
      antibody levels were highest in patients with major neurological signs. Antibody
      response was only associated with the IgM isotype. We evaluated antibody
      specificity and avidity by competition experiments using conjugates and
      nitrosylated conjugates. Avidity was around 2 x10(-6) m for the S-nitroso
      cysteine epitope and 2 x 10(-8) m for the S-nitroso-tyrosine epitope. Detection
      of circulating antibodies to S-nitroso-cysteine and S-nitroso-tyrosine epitopes
      provides indirect evidence for nitric oxide (NO) involvement in HAT and their
      levels are correlated with disease severity.

PMID- 15482404
TI  - Reliable and frequent detection of adult Wuchereria bancrofti in Ghanaian women
      by ultrasonography.
AB  - Detection of adult Wuchereria bancrofti by ultrasonography of the scrotal region
      in men is a suitable diagnostic tool for lymphatic filariasis, whereas there are
      only a few case reports of adult filariae observed by ultrasonography in women.
      We examined 35 microfilaraemic women ultrasonographically in sites of the body
      suspected as locations for worm nests. In 15 women the 'filaria dance sign' (FDS)
      was detected in various locations, some being novel, such as adult worms within
      lymphatic vessels between muscular fibres of the thighs. The surprisingly high
      number of worm nests detectable in microfilaraemic women recommends
      ultrasonography for diagnosis and treatment efficacy monitoring of female
      patients infected with W. bancrofti.

PMID- 15482405
TI  - Assessment of disease and infection of lymphatic filariasis in Northeastern
      Cambodia.
AB  - We assessed the filariasis disease burden in four northeastern provinces of
      Cambodia by using and validating a key-informant questionnaire, consisting of
      four questions, with pictures of patients with leg elephantiasis and hydrocoele.
      The questionnaire was distributed and collected through the school, health and
      administrative systems. Validation surveys included clinical examination, a card
      test for W. bancrofti (ICT Filariasis card test, AMRAD) and night blood finger
      prick examination of patients reported with clinical elephantiasis. Only 48.0% of
      questionnaires were returned. A total of 220 patients were reported, mostly from
      Stung Treng (36.8%) and Rattanakiri provinces (35.0%). Key-informants reported
      patients with lymphatic filariasis with a sensitivity of 85.7% for leg and 97.0%
      for scrotum morbidity, and with a specificity of 95.6%. However, substantial over
      reporting resulted in very low positive predictive values for elephantiasis of
      19.4% for legs and of 23.7% for the scrotum. As 97.4% of patients with clinical
      lymphatic filariasis were older than 40 years, the diagnostic performance of the
      questionnaire would be improved by restricting its use to that age group. About
      0.7% of 3490 W. bancrofti card tests were positive; the prevalence was 1.94%
      (12/618) in Rattanakiri, 0.38% (4/1055) in Stung Treng and 0.22% (2/919) in Preah
      Vihear. W. bancrofti microfilaria were identified in blood from two patients in
      Rattanakiri (0.32%) and from one patient in Stung Treng (0.09%). Brugia malayi
      microfilaria were identified in blood from five patients in Rattanakiri (0.81%)
      only. No patients with microfilariaemia were identified in Preah Vehear. In
      Mondulkiri province all investigations (card test, night blood examination,
      clinical examination) for lymphatic filariasis were negative. Our findings
      confirm the usefulness of key-informant questionnaire for the identification of
      filariasis patients provided that high adherence can be achieved. Lymphatic
      filariasis infection and disease is present in northern Cambodian provinces but
      the burdens of disease and infection are relatively low. These results are being
      used in the implementation of the national control programme for lymphatic
      filariasis.

PMID- 15482406
TI  - Mosquito nets and the poor: can social marketing redress inequities in access?
AB  - Treated mosquito nets are a practical malaria control tool. However,
      implementation of efficient delivery mechanisms remains a challenge. We
      investigated whether social marketing of treated mosquito nets results in
      decreased equity in rural Tanzania, through household surveys before the start of
      a social marketing programme and 3 years later. About 12,000 household heads were
      asked about ownership of nets and other assets including a tin roof, radio, or
      bicycle. A socio-economic status score was developed for each household. Net
      ownership was calculated for households in each quintile of this score, from
      poorest to least poor. In 1997, about 20% of the poorest households and over 60%
      of the least poor households owned a mosquito net. Three years later, more than
      half of the poorest households owned a net, as did over 90% of the least poor:
      the ratio of net ownership among the poorest to least poor increased from 0.3 in
      1997 to 0.6 in 2000. Social marketing in the presence of an active private sector
      for nets was associated with increased equity.

PMID- 15482407
TI  - Evaluation of the direct agglutination test based on freeze-dried Leishmania
      donovani promastigotes for the serodiagnosis of visceral leishmaniasis in
      Sudanese patients.
AB  - The direct agglutination test (DAT) based on freeze-dried (FD) Leishmania
      donovani antigen was evaluated for the serodiagnosis of kala-azar in a rural
      setting in eastern Sudan. The performance of the FD-DAT was compared with
      standard liquid antigen (LQ) by testing serum samples and blood samples collected
      on filter paper of microscopically and PCR-confirmed VL patients, apparently
      healthy endemic controls and patients with other relevant infectious diseases for
      the region. In the present study, the FD-DAT had a sensitivity of 96.8% and a
      specificity of 96.2%. The LQ-DAT had a sensitivity of 91.0% and a specificity of
      96.6%. A high degree of agreement (97.3%; r-value 0.94) was observed between the
      FD-DAT and the LQ-DAT, as well as between the FD-DAT performed on serum samples
      and corresponding blood samples collected on filter paper (agreement 97.8%; r
      value 0.79). The FD-DAT is very suitable as diagnostic test for kala-azar in
      remote rural conditions as it is sensitive, specific and stable. The antigen is
      affordable, reproducible and available, which contributes to the sustainability
      of the DAT as a diagnostic test for VL.

PMID- 15482408
TI  - Diarrhoea, vomiting and the role of milk consumption: perceived and identified
      risk in Bamako (Mali).
AB  - OBJECTIVES: To evaluate the public health impact of milk contamination in Bamako,
      Mali. METHODS: A case-control study assessed the risk-factors for food-borne toxi
      infections with diarrhoea and vomiting as main clinical picture. A total of 131
      schoolchildren between 5 and 20 years of age were interviewed by trained
      interviewers in schools in Bamako. A structured questionnaire was used to record
      health problems, food and particularly milk consumption habits and socio-economic
      indicators. RESULTS: Final multivariate logistic regression analysis identified
      regular consumption of boiled milk [odds ratio(OR) = 4.38; 95% CI = 1.15-16.71],
      age between 5 and 10 years (OR vs. age group 11-15 years = 3.28; 95% CI = 1.09
      9.85) and the existence of dry latrines in the household (OR = 7.65; 95% CI =
      1.92-30.55) as risk factors for diarrhoea and vomiting. Other milk products and
      the socio-economic level of the household were not significantly associated with
      the outcome. Many people were unaware of the potential risks of milk consumption.
      CONCLUSIONS: Milk products may be a risk factor for food-borne toxi-infections.
      Attention has to be paid to products considered 'safe', such as boiled or
      pasteurized milk. The low awareness of potential risks of many people may
      increase the risk of milk consumption. To achieve a sustainable increase in local
      milk production in Africa, milk quantity and production and transformation
      quality should be improved simultaneously.

PMID- 15482410
TI  - Factors that influence spontaneous reporting of adverse drug reactions: a model
      centralized in the medical professional.
AB  - RATIONALE, AIMS AND OBJECTIVES: The spontaneous reporting of adverse drug
      reactions (ADRs) through the yellow card and made concrete by the knowledge and
      attitudes of doctors, has been rousing a great deal of bibliographical interest
      in recent years. However, there does not seem to be any actual revision in the
      theme on which the theoretical models that explain the process of decision in
      reporting are proposed. In this work an explanatory model of the factors that
      condition reporting is proposed and a revision of the literature on the subject
      has also been carried out. METHODS: The proposed model is centralized in the
      medical professional and it considers the habit of reporting as the result of the
      doctor's formation and his interaction with the environment. The combination of
      knowledge-attitudes-practices and the theory of the satisfaction of needs seemed
      very adequate for ADR systematization. RESULTS AND CONCLUSIONS: The results also
      indicate that, to improve the participation of health professionals in
      surveillance systems through spontaneous reporting, it might be necessary to
      design combined strategies that modify both intrinsic (knowledge, attitudes) and
      extrinsic (relationship between health professionals and their patients, the
      national health system and pharmaceutical companies) factors.

PMID- 15482411
TI  - Prescription-related illness--a scandalous pandemic.
AB  - Prescribed drugs are now a major cause of morbidity and mortality, particularly
      in the elderly. The extent of this pandemic is described and its likely causes in
      primary care are identified: unnecessary prescribing, imprecise diagnosis,
      inadequate undergraduate and postgraduate education in pharmacology and
      therapeutics, the uncritical application of evidence-based medicine, the
      outstanding development of new drugs and their sometimes unjustified promotion.
      Urgent action is recommended under seven headings, by health administration,
      epidemiologists, medical educators and prescribing doctors.

PMID- 15482412
TI  - An evaluation of risk factors for adverse drug events associated with angiotensin
      converting enzyme inhibitors.
AB  - RATIONALE, AIMS AND OBJECTIVES: To identify potential factors leading to
      discontinuation of angiotensin-converting enzyme (ACE) inhibitors because of
      adverse drug events. METHODS: Retrospective cohort study was conducted at
      outpatient clinics affiliated with an urban tertiary care hospital. ACE
      inhibitors were administered to 2225 consecutive outpatients. RESULTS: In 19% of
      the total cohort, ACE inhibitors were discontinued because of adverse drug
      events. Cox proportional hazard model identified the following independent risk
      factors for discontinuation because of adverse drug events: age, female gender,
      ethnicity other than African American or Latino, no history of previous ACE
      inhibitor use, history of cough caused by another ACE inhibitor, hypertension,
      anxiety or depression, no hemodialysis, and elevated creatinine. History of
      smoking was shown to be a risk factor for cough [hazard ratio (HR): 2.5; 95%
      confidence interval (CI): 1.1-5.7], angioedema (HR: 2.7; 95% CI: 1.1-7.0), and
      hyperkalaemia (HR: 5.4; 95% CI: 1.3-23.2). History of ACE inhibitor-induced cough
      was not only a risk factor for cough (HR: 12.9; 95% CI: 7.5-22.3) but also for
      angioedema (HR: 9.1; 95% CI: 2.1-39.9). Patients with creatinine > or = 1.6 mg
      dL(-1) were likely to discontinue ACE inhibitors because of renal dysfunction
      (HR: 4.7; 95% CI: 1.5-12.7) and hyperkalaemia (HR: 10.9; 95% CI: 3.1-39.0). East
      Asians were more likely to develop cough (HR: 2.5; 95% CI: 1.1-5.7) and
      hyperkalaemia (HR: 80.3; 95% CI: 5.4-1190) and African Americans to develop
      angioedema (HR: 3.5; 95% CI: 1.3-8.9). CONCLUSIONS: Although further validation
      is necessary, these risk factors should help doctors identify patients with
      elevated risk for adverse drug events because of ACE inhibitors.

PMID- 15482413
TI  - Effectiveness of interferon beta treatment in relapsing-remitting multiple
      sclerosis: an Italian cohort study.
AB  - RATIONALE, AIMS AND OBJECTIVES: Randomized clinical trials (RCTs) have provided
      evidence for the efficacy of interferon beta (IFNbeta) in the treatment of
      relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to
      evaluate the effectiveness of IFNbeta treatment in clinical practice. METHODS:
      This was a national, multicentre, observational study of patients with confirmed
      RRMS. Demographic, clinical and therapeutic data were retrospectively collected
      for each patient enrolled in the study. RESULTS: The study cohort consisted of
      427 patients exposed to and 245 never exposed to IFNbeta treatment during the
      study period (for a total 2297 patient-years of follow-up). Among the exposed
      patients, 215 were initially untreated and then began IFNbeta later in the follow
      up period; 137 of these patients were exposed to IFNbeta for more than 2 years.
      In these patients, IFNbeta treatment reduced the mean relapse rate by 24.2%[95%
      confidence interval (CI): 5.8-42.5%]. For 640 of the 672 patients enrolled in the
      study, it was possible to calculate the area under the disability/time curve
      compared to that present at baseline. A total of 117 (18.3%) patients displayed
      disability progression. Adjustment of the disability progression rates for
      potential confounders and/or for propensity scores by Poisson regression model
      resulted in relative risks for patients exposed to IFNbeta treatment compared to
      those never exposed to IFNbeta of 0.87 (95% CI: 0.56-1.34) after an exposure of <
      or = 2 years, and of 0.35 (95% CI: 0.21-0.60) after an exposure of >2 years.
      CONCLUSIONS: These findings suggest that the evidence from RCTs on the treatment
      of RRMS with IFNbeta has been effectively translated into routine clinical
      practice.

PMID- 15482414
TI  - Application of hepatitis serology testing algorithms to assess inappropriate
      laboratory utilization.
AB  - RATIONALE, AIMS AND OBJECTIVES: Many studies pointed out inappropriate
      utilization of laboratory caused by excessive amounts of tests ordered by
      doctors. To prevent and to eliminate the ordering of unhelpful tests, introducing
      diagnostic algorithms, which are also a suitable practice for application to
      hepatitis serology, have been suggested. This study aimed to determine
      inappropriate test ordering rates with respect to the commonly approved
      algorithms for serological diagnosis of viral hepatitis. METHODS: To assess the
      number of inappropriate test orders, laboratory records of samples sent for
      hepatitis A, B, and D serology were reviewed and evaluated retrospectively with
      respect to algorithms for serological diagnosis of viral hepatitis. Orders
      including serological marker groups with inadequate clinical information to
      determine whether or not the order was inappropriate were excluded from the
      analysis. RESULTS: Application of diagnostic algorithms showed that 50% of anti
      HAV IgM and anti-HAV total; 12.7% of anti-HBs, 12.7% of anti-HBc total, 78.5% of
      anti-HBc IgM, 87.3% of HBe Ag, 78.8% of anti-HBe, 58.7% of anti-HD total orders
      were made inappropriately. CONCLUSIONS: Our study provides information for
      inappropriate laboratory utilization for hepatitis serology testing and we
      suggest to use diagnostic algorithms applied by the serology laboratory to
      decrease the rate of unhelpful test orders.

PMID- 15482415
TI  - An evaluation of the adequacy of outpatient monitoring of thyroid replacement
      therapy.
AB  - OBJECTIVES: Hypothyroid patients managed with excessive or insufficient thyroid
      replacement therapy are often difficult to clinically recognize. Monitoring may
      prevent or minimize the consequences of adverse drug events (ADEs). We sought to
      develop an explicit model of medication monitoring and to evaluate monitoring
      processes and ADEs in patients taking levothyroxine. METHODS: A retrospective
      chart review of 400 outpatients receiving levothyroxine therapy between 1 January
      2000 and 1 January 2001 at a large North American tertiary care hospital. We
      measured the proportion of patients satisfying minimum monitoring criteria,
      experiencing specific monitoring errors and having levothyroxine-related ADEs.
      Explicit monitoring criteria were derived from the literature and through expert
      opinion. Adverse drug events were identified using structured implicit reviews.
      RESULTS: Overall, only 56% (95% confidence interval [95% CI] 51-62%) of the
      patients prescribed levothyroxine received the minimal recommended monitoring.
      Errors were identified at all stages of the monitoring model. Patients who
      received the recommended monitoring had fewer levothyroxine-related ADEs (1% vs.
      6%, P=0.013) than those who did not. Minority status (white people 2% vs. black
      people 4% vs. Hispanics 14%, P=0.023) and primary language (English 3% vs. Non
      English 20%, P=0.002) were the patient characteristics associated with
      levothyroxine-related ADEs. CONCLUSION: Only half of outpatients taking
      levothyroxine at one tertiary care hospital received the recommended monitoring
      during one year of follow-up. Levothyroxine-related ADEs were more frequent in
      patients with lower-quality monitoring and in minorities and non-English
      speakers.

PMID- 15482416
TI  - Gender bias in cardiovascular advertisements.
AB  - RATIONALE: Women with cardiovascular disease are treated less aggressively than
      men. The reasons for this disparity are unclear. Pharmaceutical advertisements
      may influence physician practices and patient care. AIMS AND OBJECTIVE: To
      determine if female and male patients are equally likely to be featured in
      cardiovascular advertisements. METHODS: We examined all cardiovascular
      advertisements from US editions of general medical and cardiovascular journals
      published between 1 January 1996 and 30 June 1998. For each unique advertisement,
      we recorded the total number of journal appearances and the number of appearances
      in journals' premium positions. We noted the gender, age, race and role of both
      the primary figure and the majority of people featured in the advertisement.
      RESULTS: Nine hundred and nineteen unique cardiovascular advertisements were
      identified of which 254 depicted a patient as the primary figure. A total of
      20%[95% confidence interval (CI) 15.3-25.5%] of these advertisements portrayed a
      female patient, while 80% (95% CI 74.5-84.7%) depicted a male patient, P <0.0001.
      Female patient advertisements appeared 249 times (13.3%; 95% CI 8.6-18.9%) while
      male patient advertisements appeared 1618 times (86.7%; 95% CI 81.1-91.4%), P
      <0.0001. Female patient advertisements also had significantly fewer mean
      appearances than male patient advertisements in journals' premium positions (0.82
      vs. 1.99, P=0.02). Similar results were seen when the advertisements were
      analysed according to predominant gender. CONCLUSIONS: Despite increasing
      emphasis on cardiovascular disease in women, significant under-representation of
      female patients exists in cardiovascular advertisements. Physicians should be
      cognizant of this gender bias.

PMID- 15482417
TI  - First episode psychosis: a novel methodology reveals higher than expected
      incidence; a reality-based population profile in Northumberland, UK.
AB  - RATIONALE, AIMS AND OBJECTIVES: To document the natural history/clinical course
      of an unselected population presenting with first episode psychosis across a
      Mental Health Trust. METHOD: An observational database was set up covering all
      patients over 15 years of age. Data were collected at presentation and annual
      follow-up intervals. RESULTS: A total of 227 patients presented during the 3
      years initial study period with a first episode psychosis. The commonest
      diagnoses were psychotic depression 19%, paranoid schizophrenia 11%, persistent
      delusional disorder 7% and bipolar affective disorder 7.5% giving an annual
      incidence of 30.36 per 100 000 population. At presentation, half had been
      admitted to hospital, nearly half of whom were detained under the Mental Health
      Act, and only a quarter were currently employed. Twenty-six per cent had an
      episode of deliberate self-harm and 14% had harmed others. A recurring pattern
      emerged of over half the patients being no longer in contact with mental health
      services 1 year after presentation. Data collection is ongoing. CONCLUSIONS:
      Clinical and managerial cooperation achieved a practical framework for data
      collection. This approach in an unselected population of patients yielded new
      insights into the course of first episode psychosis. The higher incidence than
      expected from the literature has implications for local strategic planning and
      provides a framework for detailed evaluation of a complex patient group.

PMID- 15482418
TI  - An audit of clinical outcomes and client and referrer satisfaction with a Mood
      and Anxiety Disorders Unit.
AB  - OBJECTIVE: To evaluate outcome and client and referrer satisfaction with the
      service provided by a Mood and Anxiety Disorders Unit (MADU). METHOD: MADU was a
      specialized clinical service for the assessment and management of individuals
      suffering with affective and anxiety disorders. Clients were referred to MADU
      from a variety of health service providers. A telephone survey of 30 clients and
      20 referrers who have used the services of MADU was conducted, investigating
      outcome satisfaction with the service provided by MADU. RESULTS: Clients and
      referrers reported a high level of satisfaction with the service provided by
      MADU. There was a high degree of adherence to treatment recommendations. The mean
      Patient Global Impression of Improvement (PGI) rating by the clients before the
      MADU assessment was 2.74 (SD=1.27). In comparison the mean PGI rat-ing at the
      time of follow-up was 6.64 (SD=1.91). CONCLUSIONS: Specialist mood disorders
      units are a useful and potentially cost-effective additional service included as
      a part of a mental health service.

PMID- 15482419
TI  - Patient satisfaction profiling of individual physicians: impact of panel status.
AB  - RATIONALE, AIMS AND OBJECTIVES: Evaluation of physician performance is
      increasingly based on patient satisfaction. However, few data are available
      regarding the extent to which individual physician profiles might be influenced
      by factors such as whether a physician's practice is open or closed. We evaluated
      whether panel status (whether or not a physician is accepting new patients) is
      associated with patient satisfaction with their primary care physician (PCP).
      METHODS: Cross-sectional analysis of patient satisfaction surveys. Surveys were
      available for 1,750 patients cared for by 69 PCPs. Patient satisfaction with
      their PCP was determined based on a composite of six questions derived from the
      Medical Outcomes Study. We used Generalized Estimating Equations to adjust for
      physician level variation. RESULTS: Patients of closed-panel physicians were more
      likely to rate their satisfaction with the provider as 'Excellent' or 'Very Good'
      compared to patients of open-panel physicians (78% vs. 69%, P <0.0001). After
      adjusting for satisfaction with the practice site, provider years in practice,
      managed care coverage, provider productivity, and patient race, the association
      between a closed panel and satisfaction remained significant (odds ratio 1.60,
      95% confidence interval 1.10-2.31). CONCLUSIONS: Individual physicians' patient
      satisfaction data are confounded by factors not likely to be adjusted for in
      available profiles. After adjusting for other variables, physicians with closed
      panels still had better patient satisfaction compared to physicians with open
      panels. Further research is necessary to determine if panel status might also
      confound patient satisfaction.

PMID- 15482420
TI  - The selection of doctors.

PMID- 15482421
TI  - Environmental risk factors associated with amoebic gill disease in cultured
      salmon, Salmo salar L., smolts in Ireland.
AB  - A 2-year study was carried out on amoebic gill disease (AGD) involving monthly
      samples of 1+ Atlantic salmon, Salmo salar L., smolts, histological assessment of
      the gills and analysis of environmental data. Gill pathology was seen before
      amoebae could be detected microscopically. These changes in gill integrity were
      associated with marine environmental conditions, particularly elevated ammonium,
      nitrite and chlorophyll levels. The results suggest that the environmental
      changes predispose salmon to colonization by amoebae and ciliates. High densities
      of histophagous scuticociliates were observed in the gills during periods of
      advanced gill pathology. A number of different amoebae were observed in close
      association with gill pathology. Neoparamoeba was not seen in high densities, nor
      was it associated with gill pathology, indicating that Neoparamoeba may not be
      the primary agent of the AGD in Irish salmonid culture.

PMID- 15482422
TI  - Systemic and mucosal antibody response in tilapia, Oreochromis niloticus (L.),
      following immunization with Flavobacterium columnare.
AB  - Specific antibody responses to Flavobacterium columnare (isolate ATCC 23463T)
      were characterized in plasma and mucus of tilapia following intraperitoneal
      (i.p.) injection or immersion immunization with formalin-killed sonicated or
      whole cell preparations. Fish (30 per treatment) received a primary immunization
      and were booster immunized 4 weeks later. An enzyme-linked immunosorbent assay
      was developed for detection and quantification of specific anti-F. columnare
      antibody, and it was found that formalin-killed sonicated cells in Freund's
      complete adjuvant (FCA) injected i.p. stimulated a significant systemic antibody
      response within 2 weeks (mean titre 11,200) which increased to 30,600 following
      secondary immunization. At 10 weeks post-immunization, the mean titre remained
      significantly elevated above the controls. Antibodies were also observed in
      cutaneous mucus of fish immunized i.p. with formalin-killed sonicated cells in
      FCA at 6 and 8 weeks post-immunization (mean titres 67 and 33, respectively).
      Although some individual fish responded, mean plasma and cutaneous mucus antibody
      titres were not significantly greater than controls in any of the other treatment
      groups. The results of this study demonstrate that tilapia can mount a
      significant humoral response in plasma and cutaneous mucus to F. columnare, but
      i.p. immunization with FCA is required to elicit this response.

PMID- 15482423
TI  - Detection of koi herpesvirus in common carp, Cyprinus carpio L., by loop-mediated
      isothermal amplification.
AB  - Loop-mediated isothermal amplification (LAMP) is a novel method that amplifies
      DNA with high specificity and rapidity under isothermal conditions. In this
      study, using the LAMP method, a protocol for koi herpes virus (KHV) detection in
      common carp was designed. A set of four primers, two inner and two outer, were
      designed based on the sequence of the thymidine kinase (tk) gene of KHV. Time and
      temperature conditions for detection of KHV were optimized for 60 min at 65
      degrees C. The detection limit using LAMP was found to be similar to that by
      polymerase chain reaction. In this study, we have developed a highly sensitive
      and rapid diagnostic procedure for detection of KHV infection in common carp.

PMID- 15482425
TI  - PCR-based detection of betanodaviruses from cultured and wild marine fish with no
      clinical signs.
AB  - Betanodaviruses are the causative agents of viral nervous necrosis (VNN) or viral
      encephalopathy and retinopathy (VER) in cultured marine fish. A total of 131
      apparently healthy fish from 30 species were collected in two geographically
      remote aquaculture areas, Yashima Bay (Kagawa Prefecture) and Tamanoura Bay
      (Nagasaki Prefecture), in Japan. The brains of fish were examined by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and nested PCR to detect the
      coat protein gene of betanodavirus. In Yashima Bay, two and 13 of 20 cultured
      fish were positive for nodavirus in RT-PCR and nested PCR, respectively, and four
      of five wild fish were positive only in nested PCR. In Tamanoura Bay, 28 and 99
      of 106 wild fish were positive for the virus in RT-PCR and nested PCR,
      respectively. All the sequences of the nested PCR products (177 nt) from 27 fish
      species (10 cultured and 17 wild) were highly homologous to each other (99-100%)
      and were closely related to that of the known betanodavirus, redspotted grouper
      nervous necrosis virus (RGNNV). These results illustrate that large populations
      of cultured and wild marine fish in aquaculture areas are subclinically infected
      with genetically closely related betanodaviruses, suggesting an importance of
      such infected fish as a carrier or reservoir of betanodaviruses.

PMID- 15482424
TI  - Characterization of nodavirus and viral encephalopathy and retinopathy in farmed
      turbot, Scophthalmus maximus (L.).
AB  - An outbreak of nodavirus infection in turbot larvae is described with respect to
      histopathology, immunohistochemistry, cell culture cultivation, RT-PCR
      amplification and sequence analysis of the capsid protein gene RNA2. Affected
      turbot developed classical signs of viral encephalopathy and retinopathy (VER)
      with abnormal swimming behaviour and high mortality levels. In the acute stage of
      infection, light microscopy revealed vacuolation of the central nervous system
      (CNS), with positive immunohistochemical staining for nodavirus. Later in the
      infection, CNS lesions appeared more chronic and contained clusters of cells
      immunopositive for nodavirus. Bacterial overgrowth in the intestines of the fish
      may have provoked or influenced the course of the nodavirus infection. We were
      unable to propagate the virus in cell culture. While RT-PCR using primers
      designed to detect Atlantic halibut nodavirus gave negative results, further
      testing with primers complementary to a more conserved region of RNA2 resulted in
      amplification of a product of the expected size. The entire RNA2 segment was
      cloned and sequenced. Sequence alignment showed that the turbot nodavirus (TNV)
      was different from previously described fish nodaviruses. In addition,
      phylogenetic analysis based on an 823 nt region of the sequence indicated that
      TNV clustered outside the four established fish nodavirus genotypes, suggesting a
      fifth genotype within the betanodaviruses.

PMID- 15482426
TI  - Morphological characterization and notes on the life cycle of a newly discovered
      variant of Loma salmonae (Putz, Hoffman & Dunbar) from a natural infection of
      chinook salmon, Oncorhynchus tshawytscha (Walbaum).
AB  - Two variants of Loma salmonae occur in net-pen reared chinook salmon,
      Oncorhynchus tshawytscha. The typical variant (OA) has a host specificity for
      salmonids of the genus Oncorhynchus whereas the atypical variant (SV) has a host
      specificity for brook trout, Salvelinus fontinalis, and in this study, the
      ultrastructure of the two are compared. In fish at 8 weeks post-exposure xenomas
      of the SV variant have a very high proportion of mature spores compared with
      other developmental stages, while in xenomas of the OA variant there are fewer
      spores and many other developmental stages. Spores of the SV variant had up to 20
      turns of their polar tube whereas those of the OA variant only had 17.
      Furthermore, the spores of the SV variant were significantly larger than those of
      the OA variant. The sporophorous vesicle for both variants appears to form around
      a sporogonial plasmodia, which results in many spores developing within the
      vesicle.

PMID- 15482427
TI  - Investigation of shiga toxin-producing Escherichia coli in avian species in
      India.
AB  - AIMS: To investigate the presence or absence of shiga toxin-producing Escherichia
      coli (STEC) in avian species in India. METHODS AND RESULTS: Faecal samples
      originating from 500 chicken and 25 free flying pigeons were screened for the
      presence of E. coli. A total of 426 (chicken, 401; pigeons, 25) E. coli strains
      were isolated. Of 426 E. coli strains, 387 were grouped into 77 serogroups, while
      70 and 59 strains were untypable and rough, respectively. All isolates were
      subjected to multiplex polymerase chain reaction (m-PCR) for the detection of
      stx(1), stx(2), eaeA, hlyA and saa genes. None of the E. coli strains studied
      showed the presence of stx(1), stx(2) or their variants and saa genes. Overall 11
      (2.74%) and seven (1.74%) strains from chickens possessed eaeA and hlyA genes,
      respectively, while as only six (1.49%) strains from chickens possessed both eaeA
      and hlyA genes. O9, O8, O60 and O25 serogroups were most predominant of which
      there were 24 (5.63%), 23 (5.39%), 23 (5.39%) and 20 (4.69%) strains,
      respectively. None of the isolates from pigeons showed the presence of any of the
      virulence genes studied. CONCLUSIONS: STEC are absent in chickens and pigeons.
      However, further studies are required in this direction to confirm or contradict
      our findings. E. coli strains originating from birds are carrying a low
      percentage eaeA or hlyA genes. SIGNIFICANCE AND IMPACT OF THE STUDY: The present
      study is the first attempt to investigate STEC in chickens and free flying
      pigeons in India. The chickens and pigeons cannot be considered as important
      carrier of STEC in India.

PMID- 15482428
TI  - Five essential oils from aromatic plants of Cameroon: their antibacterial
      activity and ability to permeabilize the cytoplasmic membrane of Listeria innocua
      examined by flow cytometry.
AB  - AIMS: To investigate the antibacterial effect of five essential oils (EO)
      extracted from aromatic plants (Cymbopogon citratus, Ocimumbasilicum, Ocimum
      gratissimum, Thymus vulgaris and Zingiber officinale) of Cameroon against strains
      of Listeria monocytogenes, L. innocua and Staphylococcus aureus. The ability of
      selected EO to permeabilize the cytoplasmic membrane of L. innocua was also
      examined. METHODS AND RESULTS: The antibacterial activity of the EO determined by
      the agar diffusion method showed that T. vulgaris had the highest activity
      followed by O. gratissimum and C. citratus. Lowest activity was recorded from Z.
      officinale and O. basilicum. Significant differences in sensitivity between
      strains of Listeria and S. aureus were observed. Flow cytometry of L. innocua
      stained with carboxy-fluorescein diacetate showed that the fluorescence intensity
      of cells exposed to EO decreased faster than nonexposed cells, indicating that EO
      permeabilized the cytoplasmic membrane with the leakage of carboxy-fluorescein.
      CONCLUSIONS: Almost all the EO tested showed antibacterial activity to a
      different extent. The antibacterial effect was due to permeabilization of the
      cytoplasmic membrane. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has
      identified the preservative potential of the EO examined. The use of sensitive
      method, such as flow cytometry, is advantageous for quick generation of data on
      the antibacterial effect of EO.

PMID- 15482429
TI  - Antimicrobial activity of ultrasound-assisted solvent-extracted spices.
AB  - AIMS: The objective of this research was to determine the antimicrobial activity
      of conventional and high-intensity ultrasound-assisted (HI-US) solvent-extracted
      Thai spices, including ginger (Zingiber officinale Rose), fingerroot (Bosenbergia
      pandurata Holtt) and turmeric (Curouma longa Linn). METHODS AND RESULTS: Extracts
      were obtained using hexane, isopropanol and a 7 : 3 isopropanol : hexane mixture
      as solvents with and without HI-US. The antimicrobial activity of the extracts
      was assayed against four strains each of Listeria monocytogenes and Salmonella
      Typhimurium DT 104 using an agar dilution assay. Application of HI-US did not
      alter antibacterial activity against S. Typhimurium, but antilisterial activity
      of some HI-US spice extracts decreased. Solvent type affected antimicrobial
      efficacy of extracts with hexane producing the least antimicrobial activity.
      Fingerroot extracted with isopropanol-hexane and without HI-US had the best
      antilisterial effect while HI-US-isopropanol fingerroot extract had the greatest
      antimicrobial efficacy against S. Typhimurium. CONCLUSIONS: Application of HI-US
      reduced time of extraction to 5 min, compared with the 24 h required for
      conventional extraction and maintained antimicrobial activity against Salmonella
      but slightly reduced activity against Listeria. SIGNIFICANCE AND IMPACT OF THE
      STUDY: HI-US in combination with proper solvent selection may offer a new tool to
      optimize extraction of spice essential oil for use as antimicrobial agents, and
      reduce processing time and costs.

PMID- 15482430
TI  - A heat inducible tyrosinase with distinct properties from Bacillus thuringiensis.
AB  - AIMS: The objective of this work was to purify the tyrosinase from
      Bacillusthuringiensis subsp. kurstaki (Bt) (CCTCC AB 90010) and study its
      enzymatic properties. METHODS AND RESULTS: A 'one-step' purification method was
      used in this work, which was an easy, high-yield purification method. Tyrosinase
      activity of this purity was measured under different conditions to study its
      kinetic characterizations. The optimum pH and thermal stability of this enzyme
      were also determined. The results revealed that the tyrosinase from Bt has
      distinct properties compared with those from other sources. CONCLUSIONS: A heat
      inducible tyrosinase of a wild strain of Bt was identified and partially
      characterized. SIGNIFICANCE AND IMPACT OF THE STUDY: The distinct properties of
      Bt tyrosinase are important to the application of Bt as a biology pesticide.

PMID- 15482431
TI  - PCR-based identification and characterization of Burkholderia cepacia complex
      bacteria from clinical and environmental sources.
AB  - AIMS: To study the genotypic identification and characterization of the 119
      Burkholderia cepacia complex (Bcc) strains recovered from clinical and
      environmental sources in Japan and Thailand. METHODS AND RESULTS: Based on the
      results of analysis by 16S rDNA RFLP generated after digestion with DdeI, the Bcc
      strains were differentiated into two patterns: pattern 1 (including Burkholderia
      vietnamiensis) and pattern 2 (including B. cepacia genomovar I, Burkholderia
      cenocepacia and Burkholderia stabilis). All strains belonged to pattern 2 except
      for one strain. In the RFLP analysis of the recA gene using HaeIII, strains were
      separated into eight patterns designated as A, D, E, G, H, I, J and K, of which
      pattern K was new. Burkholderia cepacia epidemic strain marker (BCESM) encoded by
      esmR [corrected] and the pyrrolnitrin biosynthetic locus encoded by prnC were
      present in 22 strains (18%) and 88 strains (74%) from all sources, respectively.
      All esmR-positive [corrected] strains belonged to B. cenocepacia, whereas most
      prnC-positive strains belonged to B. cepacia genomovar I. CONCLUSIONS: Strains
      derived from clinical sources were assigned to B. cepacia genomovar I, B.
      cenocepacia, B. stabilis and B. vietnamiensis. The majority of Bcc strains from
      environmental sources (77 of a total 95 strains) belonged to B. cepacia genomovar
      I, whereas the rest belonged to B. cenocepacia. On the basis of genomovar
      specific PCR and prnC RFLP analysis, strains belonging to recA pattern K were
      identified as B. cepacia genomovar I. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      work provides the genotypic identification of a collection of the Bcc strains
      from Japan and Thailand. RFLP analysis of the prnC gene promises to be a useful
      method for differentiating Burkholderia pyrrocinia from B. cepacia genomovar I
      strains.

PMID- 15482432
TI  - Influence of batch or fed-batch growth on Staphylococcus epidermidis biofilm
      formation.
AB  - AIMS: To make a quantitative evaluation of the differences in biofilm formation
      by Staphylococcus epidermidis using batch and fed-batch growth systems and to
      correlate this with production of the major biofilm polysaccharide, poly-N-acetyl
      glucosamine (PNAG). METHODS AND RESULTS: Dry weight measurements of biofilms
      formed in batch and fed-batch conditions were compared with haemagglutination
      titres, which measure the amount of PNAG produced. Strains grown in batch systems
      developed less biofilm than when grown in fed-batch systems. A good correlation
      was found between the amount of biofilm formed in fed-batch systems and the
      haemagglutination titres. CONCLUSIONS: Differences in biofilm formation and PNAG
      production by S. epidermidis are dependent on the availability of nutrients, with
      higher availability correlating with more biofilm and PNAG production.
      SIGNIFICANCE OF AND IMPACT OF THE STUDY: Comparisons of the formation of biofilms
      by S. epidermidis are dependent on choosing an appropriate biofilm growth system.
      Comparability or disparity of conclusions among different investigations will be
      strongly influenced by which mode S. epidermidis biofilms are formed.

PMID- 15482433
TI  - Isolation and characterization of endophytic Streptomyces strains from surface
      sterilized tomato (Lycopersicon esculentum) roots.
AB  - AIMS: To isolate endophytic Streptomyces strains from tomato and examine their
      antimicrobial activity. METHODS: Endophytic Streptomyces strains were isolated
      using surface-sterilization methods and identified by morphological
      characteristics. Antimicrobial activities were measured by the agar plate
      sensitivity method. Antifungal activity in vivo was measured by seedling
      mortality in infested soils. RESULTS: Twenty-one per cent of endophytic
      streptomycete isolates produced antibacterial metabolites and 41% produced
      antifungal metabolites in S medium. Sixty-five per cent of the most frequently
      isolated strains inhibited the growth of Rhizoctonia solani by the antibiosis
      assay but only 32% produced metabolites active against R. solani in S medium.
      Growth promotion and enhanced disease resistance of seedlings inoculated with
      Streptomyces sp. strain S30 were observed in tomato but not in cucumber
      seedlings. CONCLUSIONS: Endophytic Streptomyces spp. strains were successfully
      isolated using stringent methods and strain S30 promoted growth and enhanced
      resistance to R. solani in tomato seedlings. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Endophytic streptomycetes showing antifungal activity in vitro and in vivo
      may indicate the potential for their use as biocontrol agents particularly of R.
      solani disease of tomato seedlings.

PMID- 15482434
TI  - Isolation and characterization of anti-Salmonella lactic acid bacteria from the
      porcine gastrointestinal tract.
AB  - AIMS: To identify lactic acid bacteria (LAB) of porcine intestinal origin with
      anti-Salmonella activity. METHODS AND RESULTS: Samples were obtained from pig
      faeces and caeca and screened for the presence of anti-Salmonella LAB. The 11
      most promising isolates were identified as belonging to the genera Lactobacillus
      and Pediococcus. The LAB exhibited large variation in their ability to survive in
      simulated gastric juice at pH 1.85. While Lactobacillus johnsonii species
      survived at levels of 80% for up to 30 min, Lactobacillus pentosus species
      declined to <0.001% in that time. All isolates tolerated porcine bile at a
      concentration of 0.3% (w/v), with some isolates capable of growth in the presence
      of up to 5% (w/v) bile. The ability of the LAB isolates to prevent Salmonella
      invasion of intestinal epithelial HT-29 cells varied, with reductions of between
      30% (Lact. pentosus) and 80% (Lactobacillus murinus spp.) observed. CONCLUSIONS:
      LAB of porcine origin were observed to survive simulated passage through the GIT
      and inhibit growth of Salmonella and its invasion of the intestinal epithelium.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The data demonstrate that some porcine
      intestinal LAB isolates may offer potential as probiotics for the reduction of
      Salmonella carriage in pigs.

PMID- 15482435
TI  - Screening of lactic acid bacteria from fermented vegetables by carbohydrate
      profiling and PCR-ELISA.
AB  - AIMS: The aim of this study was to identify potential souring agents, isolated
      from fermented plant material, by API 50 CHL assay and a molecular method based
      on polymerase chain reaction and colorimetric hybridization (PCR-ELISA). METHODS
      AND RESULTS: Forty-two strains of lactic acid bacteria derived from plant
      material were screened by taking advantage of API 50 CHL and PCR-ELISA.
      Oligonucleotide probes used for hybridization in PCR-ELISA were specific for
      lactobacilli, the Leuconostoc family, Lactobacillus pentosus/plantarum and
      Lactobacillus brevis. The hybrides were detected by a colour-developing reaction.
      Bacteria isolated from fermented cucumbers were identified as Lact. plantarum
      related (Lact. plantarum and Lact. pentosus) and Leuconostoc species. Most of the
      strains isolated from sauerkraut were identified as Lact. pentosus/plantarum.
      CONCLUSIONS: Complementary results were obtained in the identification of
      bacterial strains, isolated from fermented cucumbers and sauerkraut, by API 50
      CHL and PCR-ELISA. SIGNIFICANCE AND IMPACT OF THE STUDY: PCR-ELISA proved to be
      suitable for the screening of large numbers of bacterial isolates from fermented
      vegetables. This will be useful for the identification of strains suitable for
      the design of starter cultures for the fermentation of plant material.

PMID- 15482437
TI  - Characterization of a bacteriocin produced by Prevotella nigrescens ATCC 25261.
AB  - AIMS: To characterize the antimicrobial activity produced by Prevotella
      nigrescens ATCC 25261, and to evaluate its safety on cultured gingival
      fibroblasts. METHODS AND RESULTS: An antimicrobial activity was obtained from
      purifying the culture supernatant of Pr. nigrescens ATCC 25261. Purification of
      the active compound was achieved with ammonium sulphate precipitation followed by
      anion-exchange and gel filtration chromatography. As revealed by SDS-PAGE, the
      active fraction was relatively homogeneous, showing a protein with an approximate
      molecular weight of 41 kDa. The antimicrobial compound, named nigrescin,
      exhibited a bactericidal mode of action against Porphyromonas gingivalis,
      Prevotella intermedia, Tannerella forsythensis, and Actinomyces spp. Nigrescin
      was stable in a pH range between 6.5 and 9.5, at 100 degrees C for 10 min, and
      resistant to lyophilization. But its activity was lost after proteinase K
      treatment. Despite at very high concentrations beyond the minimum inhibitory
      concentration (MIC), nigrescin was not toxic to the gingival fibroblasts.
      CONCLUSION: Nigrescin is a novel bacteriocin produced by Pr. nigrescens ATCC
      25261. It exhibits antimicrobial activity against species that are implicated in
      periodontal diseases. The absence of toxicity on the gingival fibroblasts
      suggests the possibility in using of nigrescin for an application in periodontal
      treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Novel evidence on nigrescin
      would make Pr. nigrescens ATCC 25261 attractive in biotechnological applications
      as an antimicrobial agent in clinical dentistry.

PMID- 15482436
TI  - Incidence of antibiotic-resistant Klebsiella pneumoniae and Enterobacter species
      in freshwater wetlands.
AB  - AIMS: The aim of this study was to assess the incidence of Enterobacteriaceae
      (potential human and animal pathogens) in wetlands. METHODS: Enterobacteriaceae,
      selected from the sediments and rhizosphere of wetland plant Juncus effusus L.,
      were analysed using classical microbiological methods, API20E, API20NE, fatty
      acid analyses, and 16S rRNA sequencing. Assessed virulence factors include
      antibiotic resistance, presence of plasmids and capsules. RESULTS: Klebsiella
      pneumoniae, Enterobacter cloacae and Enterobacter asburiae, known human
      pathogens, were identified. K. pneumoniae 16S rRNA gene sequence showed the
      significant hit (E < 0.001) with the unculturable bacteria obtained from faeces
      of elderly individuals (accession number AB099804) when Genbank database was
      used. Ent. asburiae 16S rRNA gene sequence showed the significant hit with (E <
      0.001) with the unculturable bacteria obtained from the pig gastrointestinal
      tract (accession number AF371852). The rate of antibiotic resistance (<50 microg
      ml(-1)) was high for ampicillin and cephalosporins for the most strains (75.7%)
      yet low (>10 to 20 microg ml(-1)) for kanamycin, tetracycline and chloramphenicol
      for all strains tested. Capsules were detected in all investigated strains. PCR
      detected membrane protein but not chromosomally encoded beta-lactamase.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The antibiotic resistance of tested strains
      and presence of capsules (protect micro-organisms from phagocytosis) suggest that
      wetland sediments and rhizosphere present a potential reservoirs for enteric
      human and animal pathogens.

PMID- 15482438
TI  - Effects of Magnolol and Honokiol on the activities of streptococcal
      glucosyltransferases both in solution and adsorbed on an experimental pellicle.
AB  - AIMS: To investigate the inhibitory effects of Magnolol and Honokiol on the
      activity of streptococcal glucosyltransferases (Gtfs). METHODS AND RESULTS: The
      effect of Magnolol and Honokiol that inhibits the activities of streptococcal
      GtfB, GtfC, GtfD and GtfS was explored with standard assays. The results showed
      that both samples can efficiently inhibit the activity of all Gtfs in solution
      (66.4-96.3%) and adsorbed on the surface of saliva-coated hydroxyapatite (sHA)
      beads (65.5-92.7%) at concentrations between 1.25 and 5.0 mg ml(-1). Furthermore,
      Magnolol had a stronger inhibition of four kinds of Gtfs than Honokiol both in
      solution and adsorbed on the surface of sHA beads at concentrations between 0.04
      and 0.63 mg ml(-1) (P < 0.05). CONCLUSIONS: Magnolol had significant effects on
      the activities of streptococcal Gtfs. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Magnolol as a natural herb can be developed into a new oral hygiene product to
      prevent plaque formation.

PMID- 15482439
TI  - The outer membrane cytochromes of Shewanella oneidensis MR-1 are lipoproteins.
AB  - AIM: To determine if the outer membrane (OM) cytochromes OmcA and OmcB of the
      metal-reducing bacterium Shewanella oneidensis MR-1 are lipoproteins, and to
      assess cell surface exposure of the cytochromes by radioiodination. METHODS AND
      RESULTS: In anaerobic MR-1 cells grown with (3)H-palmitoleic acid, both OmcA and
      OmcB were radiolabelled. The identities of these bands were confirmed by the
      absence of each radiolabelled band in the respective mutants lacking individual
      OM cytochromes. Radioiodination of cell surface proteins in anaerobic cells
      resulted in (125)I-labelled OmcA. The identity of this band was confirmed by its
      absence in an OmcA-minus mutant. A ubiquitous radioiodinated band that migrates
      similarly to OmcB precluded the ability to determine the potential cell surface
      exposure of OmcB by this method. CONCLUSIONS: Both OmcA and OmcB are
      lipoproteins, and OmcA is cell surface exposed. SIGNIFICANCE: The lipoprotein
      modification of these OM cytochromes could be important for their localization or
      incorporation into the OM. The cell surface exposure of OmcA could allow it to
      directly transfer electrons to extracellular electron acceptors (e.g. manganese
      oxides) and is consistent with its in vivo role.

PMID- 15482440
TI  - Inhibitory activity of 2-nitropropanol against select food-borne pathogens in
      vitro.
AB  - AIMS: To test the inhibitory activity of 2-nitro-1-propanol (2NPOH) against
      Salmonella Typhimurium, Escherichia coli O157:H7 and Enterococcus faecalis.
      METHODS AND RESULTS: Specific growth rates (h(-1)) of S. Typhimurium, E. coli
      O157:H7 and Ent. faecalis were determined during culture in tryptic soya broth
      (TSB) supplemented with 0-10 mm 2NPOH. Growth rates were inhibited by 2NPOH, with
      nearly complete inhibition observed with 10 mm. Studies with S. Typhimurium
      revealed that its survivability during culture in TSB containing 5 or 10 mm 2NPOH
      was lower (P < 0.05) under aerobic than anaerobic conditions. The survivability
      of Salmonella during anaerobic culture in TSB containing 2.5 mm 2NPOH was less at
      pH 5.6 than at pH 7.0 and 8.0. No Salmonella survived anaerobic incubation in TSB
      supplemented with 10 mm 2NPOH regardless of pH. When incubated in suspensions of
      freshly collected populations of ruminal and faecal bacteria, Salmonella
      concentrations were lower (P < 0.05) in suspensions containing 10 mm 2NPOH than
      in suspensions containing no 2NPOH. CONCLUSIONS: 2NPOH inhibited S. Typhimurium,
      E. coli O157:H7 and Ent. faecalis. SIGNIFICANCE AND IMPACT OF THE STUDY: Results
      suggest that 2NPOH may be a useful antimicrobial supplement to reduce carriage of
      certain food-borne pathogens in food animals.

PMID- 15482441
TI  - Racial discrimination by low-prejudiced whites. Facial movements as implicit
      measures of attitudes related to behavior.
AB  - We investigated the relationship of implicit racial prejudice to discriminatory
      behavior. White university students chose the best of three applicants (two were
      White and one was Black) for a prestigious teaching fellowship. They then
      completed the Implicit Association Test (IAT), a measure of implicit racial bias.
      Three weeks later, participants completed a second implicit measure of racial
      bias by viewing photos of Whites and Blacks while facial electromyography (EMG)
      was recorded from sites corresponding to the muscles used in smiling and
      frowning. Analyses revealed that bias in cheek EMG activity was related to the
      race of the chosen applicant, whereas bias on the IAT was not. Motivations to
      control prejudiced reactions were not related to EMG activity or the race of the
      applicant chosen, but were related to IAT bias. The findings indicate that facial
      EMG can be used as an implicit measure of prejudice related to discrimination.

PMID- 15482442
TI  - Skimming the surface. Verbal overshadowing of analogical retrieval.
AB  - It has become almost a maxim that "talking through" a problem is advantageous.
      Contrary to this wisdom, studies from numerous domains have demonstrated that
      describing one's thought processes or analyzing a judgment may, in some
      circumstances, actually impair performance. The two experiments reported here
      built upon prior work by examining the effect of verbalization on the retrieval
      of analogies. Participants read a series of 16 short stories. Later, they were
      presented with 8 test stories and indicated whether these stories were analogies
      of the stories they had read previously. Each test story shared the same deep
      structure with one prior story and only surface characteristics with another
      prior story. Half of the participants completed the test while thinking aloud,
      and half did not think aloud. In both experiments, participants who thought aloud
      were more likely to retrieve surface matches and less likely to retrieve true
      analogies than participants who did not verbalize their thoughts during the test.

PMID- 15482443
TI  - Is consciousness a gradual phenomenon? Evidence for an all-or-none bifurcation
      during the attentional blink.
AB  - Several theories of the neural correlates of consciousness assume that there is a
      continuum of perception, associated with a gradual change in the intensity of
      brain activation. But some models, considering reverberation of neural activity
      as necessary for conscious perception, predict a sharp nonlinear transition
      between unconscious and conscious processing. We asked participants to evaluate
      the visibility of target words on a continuous scale during the attentional
      blink, which is known to impede explicit reports. Participants used this
      continuous scale in an all-or-none fashion: Targets presented during the blink
      were either identified as well as targets presented outside the blink period or
      not detected at all. We suggest that a stochastic nonlinear bifurcation in neural
      activity underlies the all-or-none perception observed during the attentional
      blink.

PMID- 15482444
TI  - Which route to recovery? Controlled retrieval and accessibility bias in
      retroactive interference.
AB  - New learning often interferes with the production of older, previously learned
      responses. However, the original responses usually appear to spontaneously
      recover and regain their dominance after a delay. This article takes a new
      approach to questions of interference and recovery by examining performance on
      immediate and delayed tests using direct or indirect instructions. Direct
      instructions asked participants to deliberately retrieve the original responses,
      and indirect instructions allowed them to respond on a more automatic basis,
      using whatever response came to mind first. Results suggest that interference and
      recovery may have their largest effects via relatively automatic influences on
      memory, such as the accessibility of new versus original information. This
      finding adds a new perspective to classic theories of interference and recovery,
      and may also inform current understanding of performance in populations (e.g.,
      older adults) that often rely predominantly on automatic memory processing.

PMID- 15482445
TI  - A sex difference in the specificity of sexual arousal.
AB  - Sexual arousal is category-specific in men; heterosexual men are more aroused by
      female than by male sexual stimuli, whereas homosexual men show the opposite
      pattern. There is reason to believe that female sexual arousal is organized
      differently. We assessed genital and subjective sexual arousal to male and female
      sexual stimuli in women, men, and postoperative male-to-female transsexuals. In
      contrast to men, women showed little category specificity on either the genital
      or the subjective measure. Both heterosexual and homosexual women experienced
      strong genital arousal to both male and female sexual stimuli. Transsexuals
      showed a category-specific pattern, demonstrating that category specificity can
      be detected in the neovagina using a photoplethysmographic measure of female
      genital sexual arousal. In a second study, we showed that our results for females
      are unlikely to be explained by ascertainment biases. These findings suggest that
      sexual arousal patterns play fundamentally different roles in male and female
      sexuality.

PMID- 15482446
TI  - Reasoning about emotional and neutral materials. Is logic affected by emotion?
AB  - In two experiments, we investigated whether people reason differently when they
      reason about emotional and neutral contents. We gave participants a conditional
      reasoning task ("If p, then q") and varied the emotionality of the items used as
      p and q. Participants were asked to draw inferences based on these statements. In
      Experiment 1, we compared statements including preexisting emotional and neutral
      words. In Experiment 2, we experimentally manipulated the emotionality of
      initially neutral words using classical conditioning. In both experiments,
      emotionality affected participants' responses. They were more likely to draw
      invalid inferences in response to emotional compared with neutral statements.

PMID- 15482447
TI  - Receptive fields for flexible face categorizations.
AB  - Abstract-Examining the receptive fields of brain signals can elucidate how
      information impinging on the former modulates the latter. We applied this time
      honored approach in early vision to the higher-level brain processes underlying
      face categorizations. Electroencephalograms in response to face-information
      samples were recorded while observers resolved two different categorizations
      (gender, expressive or not). Using a method with low bias and low variance, we
      compared, in a common space of information states, the information determining
      behavior (accuracy and reaction time) with the information that modulates
      emergent brain signals associated with early face encoding and later category
      decision. Our results provide a time line for face processing in which selective
      attention to diagnostic information for categorizing stimuli (the eyes and their
      second-order relationships in gender categorization; the mouth in expressive-or
      not categorization) correlates with late electrophysiological (P300) activity,
      whereas early face-sensitive occipito-temporal (N170) activity is mainly driven
      by the contralateral eye, irrespective of the categorization task.

PMID- 15482448
TI  - Impairment in holistic face processing following early visual deprivation.
AB  - Unlike most objects, faces are processed holistically: They are processed as a
      whole rather than as a collection of independent features. We examined the role
      of early visual experience in the development of this type of processing of faces
      by using the composite-face task, a measure of holistic processing, to test
      patients deprived of visual experience during infancy. Visually normal control
      subjects showed the expected composite-face effect: They had difficulty
      perceiving that the top halves of two faces were the same when the top halves
      were aligned with different bottom halves. Performance improved when holistic
      processing was disrupted by misaligning the top and bottom halves. Deprived
      patients, in contrast, showed no evidence of holistic processing, and in fact
      performed significantly better than control subjects when top and bottom halves
      were aligned. These findings suggest that early visual experience is necessary to
      set up or maintain the neural substrate that leads to holistic processing of
      faces.

PMID- 15482449
TI  - Development of perceptual completion in infancy.
AB  - Perceptual completion consists of bridging the gaps imposed by occlusion, such as
      perceiving the unity of center-occluded objects. It is unknown at present what
      developmental mechanisms underlie the emergence of functional perceptual
      completion in infancy. One current debate centers on the role of visible surface
      motion. According to a core-principles account, perceptual completion emerges
      simultaneously with the onset of motion discrimination, the sole determinant of
      unity percepts in infants. According to a contrasting constructivist account,
      motion discrimination is but one of several independent inputs to perceptual
      completion. In the present study, 2-month-old infants were tested for both unity
      perception and motion discrimination in partial-occlusion displays. Motion
      discrimination obtained under all conditions, even under circumstances in which
      infants were unable to perceive completion. Four-month-olds showed marked
      improvements in perceptual completion, most likely because of improvements in
      information integration. Taken together, these findings support a constructivist
      view of early perceptual and cognitive development.

PMID- 15482450
TI  - Large-number addition and subtraction by 9-month-old infants.
AB  - Do genuinely numerical computational abilities exist in infancy? It has recently
      been argued that previous studies putatively illustrating infants' ability to add
      and subtract tapped into specialized object-tracking processes that apply only
      with small numbers. This argument contrasts with the original interpretation that
      successful performance was achieved via a numerical system for estimating and
      calculating magnitudes. Here, we report that when continuous variables (such as
      area and contour length) are controlled, 9-month-old infants successfully add and
      subtract over numbers of items that exceed object-tracking limits. These results
      support the theory that infants possess a magnitude-based estimation system for
      representing numerosities that also supports procedures for numerical
      computation.

PMID- 15482451
TI  - False memories in children. Evidence for a shift from phonological to semantic
      associations.
AB  - Memory illusions in children of three age groups (5-, 8-, and 11-year-olds) were
      investigated using a modified version of the Deese-Roediger-McDermott (DRM)
      procedure. Children from each age group falsely recalled nonpresented items
      related to the study lists. However, the nature of the intrusions varied across
      the different groups. The 5-year-olds were more likely to falsely recall words
      that rhymed with the studied items than to recall unrelated items, whereas the 11
      year-olds were more likely to falsely recall words that were semantically related
      to the list theme than to produce either rhyming or unrelated intrusions.
      Intrusions made by the 8-year-olds were equally likely to be semantic, rhyming,
      or unrelated to study items. The results are consistent with the notion of a
      developmental shift from phonological to semantic associations, leading to
      qualitatively different memory distortions in children of different ages.

PMID- 15482452
TI  - Effort for payment. A tale of two markets.
AB  - The standard model of labor is one in which individuals trade their time and
      energy in return for monetary rewards. Building on Fiske's relational theory
      (1992), we propose that there are two types of markets that determine
      relationships between effort and payment: monetary and social. We hypothesize
      that monetary markets are highly sensitive to the magnitude of compensation,
      whereas social markets are not. This perspective can shed light on the well
      established observation that people sometimes expend more effort in exchange for
      no payment (a social market) than they expend when they receive low payment (a
      monetary market). Three experiments support these ideas. The experimental
      evidence also demonstrates that mixed markets (markets that include aspects of
      both social and monetary markets) more closely resemble monetary than social
      markets.

PMID- 15482454
TI  - Cooled ablation.
AB  - Research on cooled ablation has been evolving for the last 10 years. Findings and
      current applications are reviewed. A cooled ablation catheter is approved by the
      FDA for use in idiopathic ventricular tachycardia (VT) patients, based on data
      originally submitted by Cardiac Pathways, Inc. This technology has subsequently
      been used by the clinicians in atrial flutter cases, nonischemic VT, epicardial
      accessory pathways, and atrial fibrillation. The experience at Johns Hopkins
      suggests that cooled radiofrequency ablation has utility in a variety of
      situations and in some instances has come to be the ablation system of choice.

PMID- 15482455
TI  - Radiofrequency ablation of atrial flutter using large-tip electrode catheters.
AB  - The use of large-tip ablation catheters in both animal and clinical studies has
      been documented in work conducted over the last 10 years. These studies have
      demonstrated the safety and efficacy of the use of 8- and 10-mm tip ablation
      catheters in the treatment of type I isthmus-dependent atrial flutter. Shorter
      procedure times are reported with the larger-tip ablation catheters compared to
      standard 4- or 5-mm tip ablation catheters, with comparable or greater efficacy,
      no significant increase in complications, and an improved quality of life. Larger
      tip ablation electrodes do require the use of higher-power radiofrequency
      generators up to 100 W. The benefits of large-tip ablation catheters are thus
      well documented for the treatment of type I isthmus-dependent atrial flutter.

PMID- 15482456
TI  - Biophysics of ablation: application to technology.
AB  - INTRODUCTION: The question of what happens to tissue during radiofrequency (RF)
      catheter ablation continues to be asked as we evolve into the use of newer
      delivery systems. METHODS AND RESULTS: Three assumptions are made about RF
      ablation. (1) Tissue injury is thermally mediated; (2) heat transfer in tissue
      should be a predictable biophysical phenomenon; and (3) large lesion technologies
      have more or less equivalent efficacies. Based on these assumptions, predictions
      are made and discussed. Many of the predictors were proven to be true while some
      surprisingly were not. CONCLUSION: In conclusion, tissue-area injury occurs
      reproducibly at a temperature of about 50 degrees C. Heat transfer in tissue is a
      predictable phenomenon. And finally, new technologies for large lesions are all
      effective, but greater surface area of ablation was achieved with a 10-mm tip and
      greater depth was achieved with a Chilli cooled ablation catheter.

PMID- 15482457
TI  - Optimizing RF output for cooled RF ablation.
AB  - Cooled RF ablation catheters increase lesion size and facilitate ablation
      compared to standard RF ablation catheters. Cooling the ablation electrode
      increases the disparity between tissue temperature and electrode temperature,
      making use of temperature for guiding power application during ablation of less
      certain value. Appropriate energy titration is important, however, to produce
      large lesions, while avoiding overheating of tissue with steam formation leading
      to "pops." In addition to power, the rate of irrigant flow can be controlled.
      Electrode-tissue contact and orientation and the cooling effect of blood flow
      around the electrode and within the tissue are not as easily adjusted and also
      influence tissue heating. In addition to electrode temperature, a decrease in
      impedance, bubble formation detected by intracardiac ultrasound, and evidence of
      tissue heating from an effect on recorded electrograms or the arrhythmia can be
      used to guide ablation energy. Guidelines for adjusting power delivery and
      avoiding "pops" and coagulum formation are suggested.

PMID- 15482458
TI  - Cryoablation: potentials and pitfalls.
AB  - The use of cryoablation in the electrophysiology lab provides some distinct
      advantages not seen with conventional radiofrequency ablation. Ice mapping allows
      a functional assessment of a putative ablation site prior to the formation of a
      permanent lesion. This provides a distinct advantage adjacent to the AV node for
      para-hisian pathways and difficult cases of AVNRT. Cryoablation also produces
      minimal endothelial disruption and thrombus formation and causes no collagen
      shrinkage. This is likely advantageous when ablation is required within venous
      structures. There is also mounting experimental evidence that cryoablation is
      safe adjacent to the arterial system, especially within the middle cardiac vein
      or distal coronary sinus. As the technology evolves and further iterations of the
      catheter proceed, the role for this new but well-established technology is likely
      to grow.

PMID- 15482463
TI  - In locus minoris resistentiae--or not?

PMID- 15482464
TI  - The role of keratins in epidermal development and homeostasis--going beyond the
      obvious.

PMID- 15482465
TI  - Cutaneous oncology in organ transplant recipients: meeting the challenge of
      squamous cell carcinoma.

PMID- 15482466
TI  - Desmogleins 1 and 3 in the companion layer anchor mouse anagen hair to the
      follicle.
AB  - Anchorage of the hair to its follicle is of paramount importance for survival of
      rodents in the wild, and is aberrant in some human alopecias. Little is
      understood about the mechanisms responsible for hair shaft anchorage. Desmoglein
      (Dsg)3-/- (knockout) mice lose hair during telogen, but their anagen hairs remain
      anchored to the follicle. We hypothesized that Dsg1 compensates for the loss of
      Dsg3 in the anagen hair follicles of these Dsg3-/- mice. Consistent with this
      hypothesis, we found Dsg1 and Dsg3 expression overlapping in the companion layer.
      To functionally address this hypothesis, we used exfoliative toxin A (ETA) to
      inactivate Dsg1 in Dsg3-/- mice. Four hours after injection of ETA, Dsg3-/- mice,
      but not Dsg3+/+ or Dsg3+/- mice, showed striking loss of anagen hair, which was
      confirmed and quantitated by gentle tape stripping. Histology of the skin of
      these mice as well as of the tape-stripped hair showed separation between the
      outer root sheath and inner root sheath of the hair follicle, at the plane of the
      companion layer. Immunostaining for trichohyalin and K6, which highlights the
      companion layer, in skin and stripped hair confirmed the plane of separation.
      Labeling of proliferating cells with bromodeoxyuridine demonstrated that the
      matrix keratinocytes responsible for producing the hair shaft were below the
      split and remained in the follicle after loss of the anagen hair. These findings
      demonstrate the importance of the companion layer, and particularly the Dsg1 and
      Dsg3 in this layer, in anchoring the anagen hair to the follicle.

PMID- 15482467
TI  - Infrared radiation affects the mitochondrial pathway of apoptosis in human
      fibroblasts.
AB  - We have previously observed that near-infrared (IR) pre-irradiation protects
      normal human dermal fibroblasts from ultraviolet (UV) cytotoxicity in vitro.
      Here, we show that IR pre-irradiation of human fibroblasts inhibited UVB
      activation of caspase-9 and -3, leading us to study early events in the
      mitochondrial apoptotic pathway after IR irradiation. IR irradiation led to a
      partial release of cytochrome c and Smac/Diablo but not apoptosis-inducing factor
      (AIF). This was accompanied by a slight but transient decrease in the
      mitochondrial membrane potential (Deltapsim) and by the insertion of Bax into
      mitochondrial membrane. Early apoptotic events in the mitochondrial pathway thus
      occurred after IR irradiation despite a lack of caspase-9 and -3 activation. This
      could be explained by the induction by IR of the expression of heat shock protein
      Hsp27, which is known to prevent apoptosome assembly. Furthermore, the balance
      between pro-apoptotic (i.e., Bax) and anti-apoptotic (i.e., Bcl-2 or Bcl-xL)
      proteins, which was rather pro-apoptotic after IR exposure, became anti-apoptotic
      24 h later, suggesting a protective effect. Together, these actions could also
      contribute to prepare the cell to resist UVB-triggered apoptosis. Finally,
      isolated rat liver mitochondria-released cytochrome c in response to IR,
      demonstrating that mitochondria were a primary target of IR radiation.

PMID- 15482468
TI  - Protease-activated receptor-2 (PAR-2) expression in human fibroblasts is
      regulated by growth factors and extracellular matrix.
AB  - Many cell types express a membrane receptor, activated by trypsin-like proteases,
      termed protease-activated receptor-2 (PAR-2). Previous studies describing PAR-2
      expression on fibroblasts have been conflicting. In this report, we investigated
      in vitro PAR-2 expression on several fibroblast cell lines using flow cytometry,
      immunohistology, and immunoblots of cell lysates. Consistent PAR-2 expression was
      detected in cultured fibroblasts, although we observed heterogeneity of cellular
      expression among the cell lines. Some fibroblast lines expressed PAR-2
      predominantly as an intracellular protein with differing cytoplasmic staining
      patterns, whereas other fibroblast lines displayed PAR-2 primarily as a cell
      surface receptor. Immunoblots of cell lysates with polyclonal anti-PAR-2
      demonstrated a 44 kDa band, the predicted molecular weight for the PAR-2 core
      protein. Furthermore, we noted that expression of PAR-2 was subject to
      regulation. Fibroblasts grown within a collagen matrix downregulated receptor
      expression whereas increased PAR-2 expression was observed by the addition of
      fibroblast growth factors PDGF-BB and TGF-beta. This study may explain the
      previous inconsistencies in PAR-2 expression observed on tissue fibroblasts.
      Results indicate that the degree of fibroblast proliferation, attenuated by
      extracellular matrix and upregulated by growth factors, influences whether
      fibroblasts express PAR-2 and, thus, would be responsive to protease signaling.

PMID- 15482469
TI  - Lysophosphatidic acid interacts with transforming growth factor-beta signaling to
      mediate keratinocyte growth arrest and chemotaxis.
AB  - Lysophosphatidic acid (LPA, 1-acyl-glycerol-3-phosphate) plays an important role
      in diverse biological responses including cell proliferation, differentiation,
      survival, migration, and tumor cell invasion. The most prominent source of LPA is
      platelets from which it is released after thrombin activation and is assumed to
      be an essential function of this lysophospholipid in cutaneous wound closure.
      Therefore, we examined the role of LPA on biological responses of keratinocytes.
      Although LPA potently enhances keratinocyte migration, it strongly induces growth
      arrest of proliferating epidermal cells. Thus, LPA possesses analogous actions to
      transforming growth factor-beta (TGF-beta), which is also released from
      degranulating platelets at wounded sites. In contrast to LPA, the intracellular
      signaling events of TGF-beta have been clearly identified and indicate that Smad3
      is involved in chemotaxis and cell growth arrest of keratinocytes induced by this
      cytokine. Here we show that LPA, although it does not alter TGF-beta release is
      capable to activate Smad3 and results in a heteromerization with Smad4 and
      binding of the complex to its specific DNA-promoter elements. LPA completely
      fails to induce chemotaxis in Smad3-deficient cells, whereas growth inhibition is
      at least in part reduced. These findings indicate an essential role of Smad3 in
      diverse biological properties of LPA-stimulated keratinocytes.

PMID- 15482470
TI  - Evaluation of the potential role of cytokines in toxic epidermal necrolysis.
AB  - Toxic epidermal necrolysis is a rare disease observed as a consequence of adverse
      reactions to drugs. It results in the widespread apoptosis of epidermal cells and
      has a high mortality rate. The mechanisms leading to this apoptosis are not yet
      elucidated. We investigated whether the cytokines present in the blister fluid,
      which accumulates under necrotic epidermis, originated from T lymphocytes and may
      play a role in the propagation of keratinocyte apoptosis. Interferon gamma (IFN
      gamma), soluble tumor necrosis factor alpha (TNF-alpha), soluble Fas ligand (sFas
      L) were present in much higher concentration in the blister fluids of 13 toxic
      epidermal necrolysis (TEN) patients than in control fluids from burns. The
      results of RT-PCR studies, however, indicated that only IFN-gamma and to a lesser
      extent interleukin (IL)-18 were produced by mononuclear cells present in the
      fluid. That suggests that the other cytokines also present (TNF-alpha, sFas-L, IL
      10) rather originated from activated keratinocytes. Fas-L was indeed
      overexpressed on the membranes of keratinocytes in lesional skin in situ. The Th1
      profile of T lymphocyte activation found in the blister fluid of patients with
      TEN is consistent with a key role for drug-specific cytotoxic T lymphocytes (CTL)
      as previously reported, the activation of keratinocytes by IFN-gamma making them
      sensitive to cell-mediated cytolysis. We propose the hypothesis that the
      production of Fas-L, TNF-alpha, and IL-10 by keratinocytes could be a defense
      mechanism against CTL rather than a way of propagating apoptosis among epidermal
      cells.

PMID- 15482471
TI  - Expanding the phenotypic spectrum of Cx26 disorders: Bart-Pumphrey syndrome is
      caused by a novel missense mutation in GJB2.
AB  - Bart-Pumphrey syndrome (BPS) is an autosomal dominant disorder characterized by
      sensorineural hearing loss, palmoplantar keratoderma, knuckle pads, and
      leukonychia, which show considerable phenotypic variability. The clinical
      features partially overlap with Vohwinkel syndrome and Keratitis-Ichthyosis
      Deafness syndrome, both disorders caused by dominant mutations in the GJB2 gene
      encoding the gap junction protein connexin-26, suggesting an etiological
      relationship. We report here a novel GJB2 mutation N54K segregating in a family
      with BPS, which was not detected in 110 control individuals of Northern European
      ancestry. This non-conservative missense mutation lies within a cluster of
      pathogenic GJB2 mutations affecting the evolutionary conserved first
      extracellular loop of Cx26 important for docking of connexin hemichannels and
      voltage gating. Immunostaining of Cx26 in lesional palmar and knuckle skin was
      weak or absent, although its adnexal expression appeared normal and the punctate
      membrane staining of Cx26 and other epidermal connexins was not altered.
      Nevertheless, the widespread immunostaining of Cx30 throughout the spinous cell
      layers suggested a compensatory overexpression. Our results emphasize that
      pleiotropic GJB2 mutations are responsible for at least 5 overlapping
      dermatological disorders associated with syndromic hearing loss and cover a wide
      range of severity and organ involvement.

PMID- 15482472
TI  - Progressive hair loss and myocardial degeneration in rough coat mice: reduced
      lysyl oxidase-like (LOXL) in the skin and heart.
AB  - The rough coat (rc) is a spontaneous recessive mutation in mice. To identify the
      mutated gene, we have characterized the rc phenotype and initiated linkage
      mapping. The rc mice show growth retardation, cyclic and progressive hair loss,
      hyperplastic epidermis, abnormal hair follicles, cardiac muscle degeneration, and
      reduced amount of collagen and elastin in the skin and heart. The rc locus was
      mapped at 32.0 cM on chromosome 9, close to the loxl gene. Lysyl oxidase-like
      (LOXL) protein is a novel copper-containing amine oxidase that is required for
      the cross-linking of elastin and collagen in vitro. LOXL is expressed at high
      levels in the skin and heart, where the rc mice show strong phenotype. The
      expression pattern and the genetic proximity to rc suggested loxl as a potential
      candidate gene. In rc mice, the loxl mRNA was reduced in the skin and the LOXL
      protein in the heart, dermis, atrophic hair follicles, and sebaceous glands. No
      mutations, however, were identified within the coding region of loxl, and
      offspring from rc/rc and loxl null mice crossing were phenotypically normal.
      Based on these results, loxl appears non-allelic to rc. Heart- and skin-specific
      downregulation of LOXL in rc mice, however, may contribute to the extracellular
      matrix alterations and the rc phenotype.

PMID- 15482473
TI  - A novel locus for disseminated superficial porokeratosis maps to chromosome
      18p11.3.
AB  - Disseminated superficial porokeratosis (DSP) is a rare autosomal dominant
      epidermal keratinization disorder of lesions characterized by cornoid lamella
      with parakeratosis, hyperkeratosis, and loss of granular layers. The genetic
      basis for this disease is unknown. Through a proband with a diagnosis of DSP, we
      identified a large four-generation Chinese family with multiple DSP-affected
      members from Anhui province in China. After excluding the linkage of the disease
      phenotype to two known loci for disseminated superficial actinic porokeratosis in
      this family, we performed a genome-wide linkage analysis using 387 microsatellite
      markers and identified a novel disease locus for DSP at 18p11.3. Our subsequent
      fine mapping and haplotype analyses further narrowed down the disease locus into
      an 18.7 cM region between the telomere and D18S391 with a maximum two-point LOD
      (logarithm of the odds) score of 4.82 (theta =0.00) at D18S1138. Therefore, this
      study provides strong linkage evidence for a DSP locus at 18p11.3.

PMID- 15482474
TI  - Macrophages and dendritic cells constitute a major subpopulation of cells in the
      mouse dermis.
AB  - Macrophages and dendritic cells (DC) in tissues with close contact to the
      environment are of essential importance in host defense and are therefore present
      in sizeable numbers. Therefore, it is surprising that mononuclear phagocyte
      populations of the dermis have rarely been investigated in a quantitative manner.
      In this study, we examined mouse dermal skin immunophenotypically and related the
      observed numbers of observed cells to the total number of nucleated cells. These
      analyses show that about 70% of all dermal cells represent CD45+ leukocytes. The
      vast majority of these cells (approximately 60% of total) expresses the
      mononuclear phagocyte markers mMGL (ER-MP23), F4/80 and CD11b. In addition, these
      cells show avid phagocytic capacity and thus are identified as dermal
      macrophages. Different subpopulations can be defined using markers such as
      sialoadhesin, ER-HR3 and mSIGN-R1 (ER-TR9). Interestingly, MHC class II
      expression differs significantly between dermal cells from ear versus back skin.
      Moreover, we have identified small populations of dermal DC and migrating
      Langerhans cells (together approximately 10% of total). In summary, our findings
      show that mononuclear phagocyte populations form the majority of dermal cells and
      thus have been clearly underestimated so far.

PMID- 15482475
TI  - Expression of CD200 on epithelial cells of the murine hair follicle: a role in
      tissue-specific immune tolerance?
AB  - CD200 (OX-2) is a transmembrane glycoprotein that transmits an immunoregulatory
      signal through the CD200 receptor (CD200R) to attenuate inflammatory reactions
      and promote immune tolerance. CD200 expression in the skin has not been described
      previously. We now report that freshly isolated cells of the murine epidermis
      contain a subpopulation of major histocompatibility complex (MHC) class II
      negative, CD3-negative keratinocytes that are CD200-positive. CD200 expression
      was accentuated in keratinocytes comprising the outer root sheath of the murine
      hair follicle (HF). When syngeneic skin grafts were exchanged between gender
      matched wild-type (WT) and CD200-deficient C57BL/6 mice, significant
      perifollicular and intrafollicular inflammation was observed, eventually leading
      to the destruction of virtually all HF (alopecia) without significant loss of the
      CD200-negative grafts. Minimal and transient inflammation was observed in WT
      grafts, which persisted long term with hair. There was a 2-fold increase in graft
      infiltrating T cells in CD200-deficient skin at 14 d. Alopecia and skin lesions
      were induced in CD200-deficient hosts by adoptive transfer of splenocytes from WT
      mice previously grafted with CD200-negative skin, but not from mice grafted with
      WT skin. Collectively, these results suggest that the expression of CD200 in
      follicular epithelium attenuates inflammatory reactions and may play a role in
      maintaining immune tolerance to HF-associated autoantigens.

PMID- 15482476
TI  - Non-invasive visualization of epidermal responses to injury using a fluorescent
      transgenic reporter.
AB  - We describe transgenic mice in which expression of a reporter, the yellow
      fluorescent protein (YFP), is locally activated in epidermal cells at sites of
      injury. YFP is detectable a day after injury; its levels peak within 3 d, and
      then decline over the subsequent week. Expression is also activated by a chemical
      irritant, and is suppressed by topical administration of hydrocortisone. These
      mice permit non-invasive time-lapse monitoring of responses to injury in vivo.
      They can be used to detect epidermal activation and to test agents that may
      provoke or attenuate epidermal responses.

PMID- 15482477
TI  - The development and characterization of an in vitro model of psoriasis.
AB  - In this study, the phenotype of psoriatic keratinocytes and fibroblasts in
      reconstructed skin models was compared to those constructed from normal cells.
      Characterization of this model by immunohistochemistry showed that classical
      markers of keratinocyte differentiation exhibited similar patterns of
      distribution in the psoriatic models to those derived from normal cells and
      generally reflected in vivo observations. Some crucial differences, however, were
      observed between normal and psoriatic models when pro-inflammatory gene
      expression and keratinocyte proliferation were investigated. Notably, the
      chemokine receptor CXCR2 was overexpressed in the psoriatic models, and,
      moreover, was localized to the granular layer of keratinocytes as seen in
      psoriasis in vivo. Pro-inflammatory genes (tumor necrosis factor alpha [TNF
      alpha], interferon gamma [IFN-gamma], and interleukin 8 [IL-8]) were expressed at
      high levels in the psoriatic models, but were only minimally expressed in the
      normal models. Models derived from uninvolved psoriatic skin showed the same gene
      expression profile as those derived from involved skin along with an increased
      proliferation rate when compared to normal models. These results suggest that
      psoriatic individuals possess an inherent predisposition to develop the disease
      phenotype even in the absence of T cells. This study represents a comprehensive
      characterization of psoriatic human skin reconstructed in vitro, and demonstrates
      the potential of this model as a valuable tool in drug discovery.

PMID- 15482478
TI  - Quantitative assessment of the transport of elastic and rigid vesicle components
      and a model drug from these vesicle formulations into human skin in vivo.
AB  - The aim of this study was to quantitatively assess the distribution profiles of
      elastic and rigid vesicle material in human skin in vivo. Furthermore, the
      distribution profiles of the model drug ketorolac applied in these vesicle
      formulations was investigated. A deuterium-labelled phospholipid was incorporated
      into these vesicles to serve as a marker for the vesicle material. The vesicles
      were loaded with ketorolac at saturated concentrations. Vesicle solutions were
      applied non-occlusively onto the skin and the treated site was sequentially tape
      stripped. Tape-strips were analyzed for vesicle material using attenuated total
      reflectance-Fourier transform infrared spectroscopy and for ketorolac by
      extraction of the tape-strips followed by high pressure liquid chromatography.
      Distribution profiles in the stratum corneum (SC) were obtained for the elastic
      and rigid vesicle material and for the ketorolac. These profiles have suggested
      that elastic vesicle material can rapidly enter the deeper layers of the SC and
      can reach almost the SC-viable epidermal junction. Rigid vesicle material,
      however, did not penetrate deep into the SC. Furthermore, the elastic vesicles
      were better than the rigid vesicles in the enhancement of ketorolac transport
      into human SC. The distribution profile of ketorolac in the deeper SC layers was,
      however, different from that of the vesicle material. This suggests that once the
      elastic vesicles partition into the SC, the ketorolac is released from the
      vesicles. The elastic vesicles are superior to the rigid vesicles both in terms
      of vesicular transport into the SC and in terms of therapeutic potential as a
      skin delivery vehicle.

PMID- 15482479
TI  - Acylceramide head group architecture affects lipid organization in synthetic
      ceramide mixtures.
AB  - The lipid organization in the upper layer of the skin, the stratum corneum (SC),
      is important for the skin barrier function. This lipid organization, including
      the characteristic 13 nm lamellar phase, can be reproduced in vitro with mixtures
      based on cholesterol, free fatty acids and natural as well as synthetic ceramides
      (CER). In human SC, nine CER classes have been identified (CER1-CER9). Detailed
      studies on the effect of molecular structure of individual ceramides on the SC
      lipid organization are only possible with synthetic lipid mixtures, as their
      composition can be accurately chosen and systematically modified. In the present
      study, small-angle X-ray diffraction was used to examine the organization in
      synthetic lipid mixtures of which the synthetic ceramide fraction was prepared
      with sphingosine-based CER1 or phytosphingosine-based CER9. The latter
      acylceramide contains an additional hydroxyl group at the sphingoid backbone. The
      results show that a gradual increase in CER1 level consistently promotes the
      formation of the 13 nm lamellar phase and that partial replacement of CER1 by
      CER9 does not affect the phase behavior. Interestingly, complete substitution of
      CER1 with CER9 reduces the formation of the long periodicity phase and results in
      phase separation of CER9.

PMID- 15482480
TI  - Pharmacological characterization of loss of function mutations of the human
      melanocortin 1 receptor that are associated with red hair.
AB  - Variation in skin color is the major host risk factor for melanoma and other
      forms of skin cancer. Individuals with red hair show an increased ratio of
      phaeomelanin to eumelanin in both hair and skin. This ratio is regulated by the
      melanocortin (MC) 1 receptor. There are several common point mutations in the
      human MC1 receptor that are overrepresented in North European red-heads, and in
      individuals with pale skin. In order to determine the functional significance of
      these mutations, we expressed the Asp84Glu, Val92Met, Arg163Gln, and Asp294His
      variants of the human MC1 receptors in eukaryotic cells and determined their
      ability to bind alpha-melanocyte stimulating hormone (MSH) peptides and increase
      intracellular cAMP. The mutants Asp84Glu and Asp294His showed a much lower
      response to alpha-MSH in cAMP and a slightly impaired ability to bind alpha-MSH,
      and the Val92Met mutant bound alpha-MSH with 100-fold lower affinity as compared
      with the wild-type. The Arg163Gln variant, widely found in some Asian
      populations, reached normal level of cAMP response but had just slightly lower
      potency for alpha-MSH in binding and second messenger studies. The results
      provide important pharmacological characterization of common MC1 receptor
      variants in various world populations.

PMID- 15482481
TI  - Larval melanocyte regeneration following laser ablation in zebrafish.
AB  - A method to specifically ablate melanocytes in a genetically tractable organism
      would facilitate the analysis of melanocyte regeneration and regulation. We have
      demonstrated that a Q-switched neodymium:yttrium-aluminum-garnet dermatology
      laser kills larval melanocytes in zebrafish. Following melanocyte ablation, new
      melanocytes regenerate from unpigmented precursors. We show that melanocyte
      regeneration following laser ablation requires kit receptor tyrosine kinase.

PMID- 15482483
TI  - Phenotypical and molecular profiling of the extraneuronal cholinergic system of
      the skin.
AB  - We present molecular and protein profiling of all acetylcholine receptors (ACh-R)
      in human scalp skin using PCR, in situ hybridization and double-labeling
      immunofluorescence. Within the epidermis, the nicotinic (n)ACh-R subunits,
      alpha3, alpha5, beta2, and beta4 were expressed in the basal cell layer (BCL) and
      in a single cell layer in the stratum granulosum; alpha9 was expressed in the
      basal and lower spinous layers. alpha7, alpha10, and beta1 were preferentially
      detected in the upper spinous and granular layers. Of the muscarinic (m)ACh-R, m1
      and m4 were found in the suprabasal layers, whereas m2, m3, and m5 remained
      restricted to the lower layers. In the outer root sheath of the hair follicle,
      all ACh-R except alpha9, beta1, and m4 were found in the BCL whereas the alpha9,
      m4, and m5 ACh-R were restricted to the central cell layer. The alpha5, beta1,
      beta2, m1-m4 chains were strongly expressed in the inner root sheath.
      Undifferentiated sebocytes expressed the alpha3, alpha9, beta4, m3-m5 ACh-R
      whereas alpha7, beta2, beta4, m2, and m4 were found in mature sebocytes. In sweat
      glands, the alpha3*, alpha7, and m2-m5 ACh-R were most prominent in the
      myoepithelial cells whereas alpha9, beta2, m1, m3, and m4 ACh-R were present in
      the acinar cells. Taken together, our data result in a complete molecular map of
      the extraneuronal cholinergic system of the skin that may be translated into
      distinct functional reaction patterns.

PMID- 15482482
TI  - Phosphatidylinositol 3-kinase/Akt-dependent and -independent protection against
      apoptosis in normal human melanocytes.
AB  - Normal human melanocytes require the synergistic action of several growth
      promoting agents for their growth in serum-free medium. The ability of four
      representative growth promoting agents including insulin, 12-O
      tetradecanoylphorbol-13-acetate (TPA), basic fibroblast growth factor (bFGF), and
      3-isobutyl-1-methylxanthine (IBMX), (iTbI) to protect melanocytes against
      apoptosis was examined. Also, the involvement of phosphatidylinositol (PI) 3
      kinase and Akt, one of the downstream targets of PI 3-kinase, in the survival
      signaling pathway was examined. The percentage of apoptotic cells was negligible
      when the cells were grown in the presence of iTbI. Deprivation of iTbI from the
      culture medium for 72 h caused approximately 30% of melanocytes to undergo
      apoptosis and this was suppressed to variable extents by the addition of one of
      the iTbI to the medium. Insulin and TPA protected against apoptosis almost
      completely, whereas bFGF and IBMX rescued melanocytes from apoptosis to a lesser
      extent. Wortmannin, an inhibitor of PI 3-kinase, potently inhibited the
      protective effect of insulin on melanocytes, whereas it did not block the ability
      of TPA, bFGF, or IBMX to rescue the cells from apoptosis. Furthermore, apoptosis
      of melanocytes induced by deprivation of iTbI was prevented almost completely by
      infection with an adenovirus vector encoding a constitutively active mutant of
      either PI 3-kinase or Akt. These results indicate that melanocytes can operate
      both PI 3-kinase/Akt-dependent and -independent mechanisms for protection against
      apoptosis and that activation of the PI 3-kinase/Akt pathway is sufficient for
      protection against apoptosis induced by deprivation of growth-promoting agents.

PMID- 15482484
TI  - UVB radiation-mediated expression of inducible nitric oxide synthase activity and
      the augmenting role of co-induced TNF-alpha in human skin endothelial cells.
AB  - Nitric oxide (NO) plays a pivotal role in ultraviolet radiation-induced
      inflammation in human skin. We had earlier reported on the inducible nitric oxide
      synthase (iNOS) inducing activity of UVA radiation. We now demonstrate that UVB
      exposure induces expression of the iNOS in vessel endothelia of normal human skin
      and in cultured human dermal endothelial cells (HUDEC), although by a molecular
      mechanism different from UVA-mediated induction. With HUDEC, UVB induces iNOS
      expression and leads to significant enzyme activities, although at app. 5-fold
      lower levels than can be achieved with proinflammatory cytokines. In contrast to
      our earlier observation with UVA, cytokine-challenge combined with simultaneous
      UVB-exposure had no additive effects on iNOS expression nor activity.
      Interestingly, a time-delay between UVB-irradiation and cytokine-challenge
      enhances endothelial iNOS enzyme activity 2.5-fold over cytokines activation
      only. This time-dependent effect strongly correlates with UVB-induced endothelial
      TNF-alpha expression. In HUDEC addition of TNF-alpha results in enhanced
      expression of the inducible arginine transporter system CAT-2 essential for
      substrate supply and thus iNOS activity. In summary, UVB induces iNOS mRNA and
      enzyme activity in HUDEC. Moreover, UVB augments CAT-2 expression through a TNF
      alpha- dependent mechanism which essentially contributes to increased iNOS
      activity.

PMID- 15482485
TI  - Physiological variation in the erythemal response to ultraviolet radiation and
      photoadaptation.
AB  - We have studied the cutaneous response to ultraviolet radiation, measured
      objectively as erythema in a sample of 12 body sites on 15 Northern European
      subjects with multiple doses of ultraviolet B (UVB). Skin pigmentation and the
      development of photoadaptation in response to five repeated doses of irradiation
      at three body sites was also measured. We report striking differences of up to 5
      fold at different body sites to the same challenge dose (p < 0.001) and
      demonstrate that for this population, site variation is just as important as
      between-person variation. Skin color at each body site is a strong predictor of
      response (p < 0.001) and that this cannot be attributed to vascular differences,
      but instead we believe it reflects site-specific variations in melanin
      pigmentation. We also observed similar but smaller within-person effects for
      responses to another inflammatory agent, dithranol (p < 0.01). Despite this, we
      did not find evidence for differences in the development of photoadaptation by
      body site. These results have clear clinical implications for the practice of
      phototesting prior to commencing phototherapy, for therapeutic failure in sites
      such as the legs in patients with psoriasis, and perhaps for melanoma body-site
      distribution.

PMID- 15482486
TI  - The time course of photoadaptation and pigmentation studied using a novel method
      to distinguish pigmentation from erythema.
AB  - The dynamics of human pigmentation in response to ultraviolet radiation (UVR)
      remain poorly characterized. In part, this is attributable to methodological
      issues relating to the overlap in spectra of hemoglobin and melanin. We describe
      a new method, based on the recording of reflectance properties following
      iontophoresis of a potent vasoconstrictor, noradrenaline. This removes the
      influence of blood, allowing measurement of pigmentation, represented as L* on
      the L*a*b* scale. Blood flow was separately assessed using laser Doppler
      flowmetry. We show that there is a clear dose response with the dose of UVR
      administered, that pigmentation peaks at 1 wk and declines over the following 10
      wk, but does not return to baseline within this period. We show clear differences
      in the degree, but not the temporal pattern of pigmentation between different
      pigmentary groups. We also report that the relation between facultative pigment
      and constitutive pigment is incomplete, with a wide scatter of responses for the
      development of pigmentation irrespective of constitutive levels. For comparison
      we also document overall photoadaptation and relate changes in pigmentation to
      the overall changes in photoadaptation.

PMID- 15482487
TI  - Loss of keratin 10 leads to mitogen-activated protein kinase (MAPK) activation,
      increased keratinocyte turnover, and decreased tumor formation in mice.
AB  - Keratin 10 (K10) is the major protein in the upper epidermis where it maintains
      keratinocyte integrity. Others have reported that K10 may act as a tumor
      suppressor upon ectopic expression in mice. Although K10(-/-) mice show
      significant epidermal hyperproliferation, accompanied by an activation of the
      mitogen-activated protein kinase (MAPK) pathway, they formed no spontaneous
      tumors. Here, we report that K10(-/-) mice treated with 7,12
      dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)
      developed far less papillomas than wild-type mice. BrdU(5-bromo-2'-deoxyuridine)
      labeling revealed a strongly accelerated keratinocyte turnover in K10(-/-)
      epidermis suggesting an increased elimination of initiated keratinocytes at early
      stages of developing tumors. This is further supported by the absence of label
      retaining cells 18 d after the pulse whereas in wild-type mice label-retaining
      cells were still present. The concomitant increase in K6, K16, and K17 in K10
      null epidermis and the increased motility of keratinocytes is in agreement with
      the pliability versus resilience hypothesis, stating that K10 and K1 render cells
      more stable and static. The K10(-/-) knockout represent the first mouse model
      showing that loss of a keratin, a cytoskeletal protein, reduces tumor formation.
      This is probably caused by an accelerated turnover of keratinocytes, possibly
      mediated by activation of MAPK pathways.

PMID- 15482488
TI  - EGFR enhances early healing after cutaneous incisional wounding.
AB  - The epidermal growth factor receptor (EGFR) has been implicated in the regulation
      of wound healing. In order to directly evaluate the role of endogenous EGFR in
      cutaneous incisional wound healing, we examined EGFR null- and wild-type skin
      after injury. By 5 d after wounding, re-epithelialization was complete in all
      EGFR wild-type wounds, but in only 40% of EGFR null wounds. Delayed wound closure
      in EGFR null skin was accompanied by an increase in edema, longer lasting and
      more prominent eschar, and increased distance between apposing wound edges. EGFR
      altered neutrophil and mast cell infiltration, and enhanced angiogenesis. EGFR
      enhanced epithelial proliferation during the first 3 d following injury, although
      proliferation was greater in EGFR null wounds at 5 d. Although migration was
      decreased in EGFR null keratinocytes cultured with standard medium or in medium
      supplemented with transforming growth factor-alpha when compared with controls,
      the addition of the wound-associated motogen keratinocyte growth factor
      eliminated the differences between genotypes. Epithelial migration into the wound
      was decreased in EGFR null skin, suggesting that both EGFR-dependent and 
      independent mechanisms regulate migration during wound healing. These data
      demonstrate that EGFR regulates multiple facets of cutaneous wound healing,
      including inflammation, wound contraction, proliferation, migration, and
      angiogenesis.

PMID- 15482489
TI  - Method of mutation analysis may contribute to discrepancies in reports of
      (V599E)BRAF mutation frequencies in melanocytic neoplasms.

PMID- 15482490
TI  - An in vivo competitive repopulation assay system to evaluate human keratinocyte
      stem cells.

PMID- 15482491
TI  - Alpha-lipoic acid is ineffective as a topical antioxidant for photoprotection of
      skin.

PMID- 15482492
TI  - An association between ulcerative colitis and atopic dermatitis, diseases of
      impaired superficial barriers.

PMID- 15482494
TI  - Annotation: understanding the development of psychopathy.
AB  - BACKGROUND: Psychopaths are not only antisocial, but also have a callous and
      unemotional personality profile. This article selectively reviews evidence that
      psychopathic personality traits are an important factor in understanding and
      predicting the development of persistent antisocial conduct. Cognitive
      neuroscience research and more tentative genetic work on psychopathy will be
      discussed, especially as they relate to possible developmental trajectories to
      psychopathy. RESULTS: A personality-based approach has been successful in
      clarifying the conceptual boundaries of psychopathy and delineating a group of
      antisocial individuals with a distinct profile of offending and clear
      neurocognitive markers indicating problems in processing distress in others and
      punishment directed to oneself. These markers are also present in children with
      psychopathic tendencies, suggesting that psychopathy may be a developmental
      disorder. The neurocognitive profile relates to the callous and unemotional
      personality traits at the core of psychopathy and may index particular
      vulnerability to persistent antisocial conduct. Preliminary twin studies suggest
      that personality traits at the core of psychopathy are much more highly heritable
      than other personality traits. There are as yet no molecular genetic studies of
      psychopathy. CONCLUSIONS: It is argued that an interdisciplinary approach that
      integrates cognitive neuroscience and genetics will enhance understanding of the
      development of psychopathy.

PMID- 15482495
TI  - Practitioner review: stress intervention for parents of children with
      intellectual disabilities.
AB  - BACKGROUND: Parents of children with intellectual disabilities are at increased
      risk for stress and other mental health problems. The purpose of the present
      review is to consider the evidence base for psychological intervention to
      remediate stress in these parents. METHODS: A selective review of interventions
      designed to reduce stress in parents of children with intellectual disabilities,
      with a focus on group interventions that incorporate various cognitive
      behavioural techniques. RESULTS: Research evidence suggests that standard service
      models (e.g., respite care, case management) probably help to reduce parental
      stress. The strongest evidence base is for cognitive behavioural group
      interventions, especially for the reduction of stress in mothers. Some data also
      indicate the potential value of parent-led support networks. CONCLUSIONS: More
      research and clinical development are needed to establish a firmer evidence base
      for stress interventions with parents of children with intellectual disabilities.
      There are also a number of potential practical implications of reducing parental
      stress for maximising the efficacy of general parent training interventions and
      also behavioural programmes for children's challenging behaviours.

PMID- 15482496
TI  - Time trends in adolescent mental health.
AB  - BACKGROUND: Existing evidence points to a substantial rise in psychosocial
      disorders affecting young people over the past 50 years (Rutter & Smith, 1995).
      However, there are major methodological challenges in providing conclusive
      answers about secular changes in disorder. Comparisons of rates of disorder at
      different time points are often affected by changes in diagnostic criteria,
      differences in assessment methods, and changes in official reporting practices.
      Few studies have examined this issue using the same instruments at each time
      point. METHODS: The current study assessed the extent to which conduct,
      hyperactive and emotional problems have become more common over a 25-year period
      in three general population samples of UK adolescents. The samples used in this
      study were the adolescent sweeps of the National Child Development Study and the
      1970 Birth Cohort Study, and the 1999 British Child and Adolescent Mental Health
      Survey. Comparable questionnaires were completed by parents of 15-16-year-olds at
      each time point (1974, 1986, and 1999). RESULTS AND CONCLUSIONS: Results showed a
      substantial increase in adolescent conduct problems over the 25-year study period
      that has affected males and females, all social classes and all family types.
      There was also evidence for a recent rise in emotional problems, but mixed
      evidence in relation to rates of hyperactive behaviour. Further analyses using
      longitudinal data from the first two cohorts showed that long-term outcomes for
      adolescents with conduct problems were closely similar. This provided evidence
      that observed trends were unaffected by possible changes in reporting thresholds.

PMID- 15482497
TI  - Behavioral and emotional adjustment, family functioning, academic performance,
      and social relationships in children with selective mutism.
AB  - This study addressed four questions which parents of children with selective
      mutism (SM) frequently ask: (1) Is SM associated with anxiety or oppositional
      behavior? (2) Is SM associated with parenting and family dysfunction? (3) Will my
      child fail at school? and (4) Will my child make friends or be teased and
      bullied? In comparison to a sample of 52 community controls, 52 children with SM
      were more anxious, obsessive, and prone to somatic complaints. In contrast,
      children with SM were less oppositional and evidenced fewer attentional
      difficulties at school. We found no group differences in family structure,
      economic resources, family functioning, maternal mood difficulties, recreational
      activities, or social networks. While parents reported no differences in
      parenting strategies, children with SM were described as less cooperative in
      disciplinary situations. The academic (e.g., reading and math) and classroom
      cooperative skills of children with SM did not differ from controls. Parents and
      teachers reported that children with SM had significant deficits in social
      skills. Though teachers and parents rated children with SM as less socially
      assertive, neither teachers nor parents reported that children with SM were
      victimized more frequently by peers.

PMID- 15482499
TI  - Perceived support in sibling relationships and adolescent adjustment.
AB  - BACKGROUND: Siblings may support each other, but also reveal fierce rivalry and
      mutual aggression. Supportive sibling relationships have been linked to the
      development of psychosocial competence of children. In the present longitudinal
      study, we will focus on the development of perceived support in sibling dyads and
      on the influence of sibling support and sibling problem behavior on psychosocial
      adjustment in adolescence. METHOD: In a three-wave longitudinal sample of 285
      Dutch families with two adolescent children (11- to 15-year-olds), these two
      siblings judged the support perceived from each other. In addition, they
      themselves and their parents judged their internalizing and externalizing problem
      behaviors. The relation of sibling support and sibling problem behavior with
      internalizing and externalizing problem behaviors was examined while controlling
      for support from parents and friends and, over time, controlling for the
      autoregressive effects of problem behavior. RESULTS: Support perceived from a
      sibling is mostly negatively related to externalizing problems; sibling problem
      behavior is strongly related to internalizing problems. Differential
      developmental trajectories of adolescents' adjustment are associated with
      siblings' support and problem behavior. CONCLUSION: The results indicate that
      adolescents' relationships with both older and younger siblings are characterized
      by modeling processes.

PMID- 15482498
TI  - Loneliness and social adaptation in Brazilian, Canadian, Chinese and Italian
      children: a multi-national comparative study.
AB  - BACKGROUND: Research on children's loneliness has been conducted mostly in
      Western, especially North American, cultures. The purpose of the study was to
      examine relations between loneliness and social adaptation among children and
      adolescents in four different societies. METHODS: A total of 2263 children from
      grade 3 to grade 6, aged 9 to 12 years, in Brazil, Canada, P. R. China, and
      Southern Italy participated in the study. The participants completed a self
      report measure of loneliness. Information about social behaviors and peer
      relationships was obtained from peer assessments. RESULTS: Multi-group analyses
      revealed that the overall patterns of relations among social behaviors, peer
      relationships and loneliness differed across the samples. Specifically,
      sociability was positively associated with peer relationships and made negative
      indirect contributions to loneliness through peer relationships in all four
      samples. Aggression made significant indirect contributions to the prediction of
      loneliness in Chinese children, but not in other samples. Shyness-sensitivity was
      associated with loneliness directly in Brazilian and Italian children and
      indirectly through peer relationships in Canadian children, but not associated
      with loneliness in Chinese children. CONCLUSIONS: The results suggest that the
      nature of children's loneliness may be affected by the broad socio-cultural
      context.

PMID- 15482500
TI  - The relation between the absolute level of parenting and differential parental
      treatment with adolescent siblings' adjustment.
AB  - BACKGROUND: The present study extends existing studies on the role of
      differential parental treatment in explaining individual differences in
      adolescent problem behaviors above the absolute level of parenting and clarifies
      the function of gender of the child, birth rank and gender constellation of the
      sibling dyads. METHOD: The absolute level of parenting practices and differential
      treatment were examined in a sample of 288 Dutch families consisting of two
      parents and two adolescents. Parents reported on adolescent internalizing and
      externalizing problem behavior and adolescents reported on parental warmth and
      coercive control. RESULTS: Parenting dimensions were related to problem behavior
      for same- and mixed-gender sibling pairs, with coercive control as the strongest
      predictor. No direct association was found between differential parental
      treatment and child outcomes above the absolute levels of parenting in same
      gender sibling pairs. However, differential maternal and paternal control was
      related to internalizing behavior of girls and differential paternal warmth was
      linked to externalizing behavior of the older siblings in mixed-gender sibling
      pairs. CONCLUSION: Differential parental treatment is uniquely associated with
      child problem behavior above the absolute level of parenting for girls and early
      born children in mixed-gender sibling pairs. Any examination of the effects of
      differential treatment should not be undertaken without considering the gender
      and birth rank of the sibling pairs.

PMID- 15482501
TI  - Children raised in fatherless families from infancy: a follow-up of children of
      lesbian and single heterosexual mothers at early adolescence.
AB  - BACKGROUND: An increasing number of lesbian women and single heterosexual women
      are bringing up children with no male involvement. This study follows up to
      adolescence a sample of children raised in fatherless families from birth or
      early infancy. METHODS: Twenty-five lesbian mother families and 38 families
      headed by a single heterosexual mother were compared with 38 two-parent
      heterosexual families. The quality of parenting by the mother, and the social and
      emotional development of the child, were assessed using standardised interview
      and questionnaire measures administered to mothers, children and teachers.
      RESULTS: Children in fatherless families experienced more interaction with their
      mother, and perceived her as more available and dependable than their peers from
      father-present homes. However, there were no group differences in maternal warmth
      towards the children. Mothers raising their child without a father reported more
      severe disputes with their child than did mothers in father-present families. The
      children's social and emotional development was not negatively affected by the
      absence of a father, although boys in father-absent families showed more feminine
      but no less masculine characteristics of gender role behaviour. No major
      differences in parenting or child development were identified between families
      headed by lesbian and single heterosexual mothers. CONCLUSIONS: The presence or
      absence of a father in the home from the outset does appear to have some
      influence on adolescents' relationships with their mothers. However, being
      without a resident father from infancy does not seem to have negative
      consequences for children. In addition, there is no evidence that the sexual
      orientation of the mother influences parent-child interaction or the
      socioemotional development of the child.

PMID- 15482502
TI  - A new social communication intervention for children with autism: pilot
      randomised controlled treatment study suggesting effectiveness.
AB  - BACKGROUND: Psychosocial treatments are the mainstay of management of autism in
      the UK but there is a notable lack of a systematic evidence base for their
      effectiveness. Randomised controlled trial (RCT) studies in this area have been
      rare but are essential because of the developmental heterogeneity of the
      disorder. We aimed to test a new theoretically based social communication
      intervention targeting parental communication in a randomised design against
      routine care alone. METHODS: The intervention was given in addition to existing
      care and involved regular monthly therapist contact for 6 months with a further 6
      months of 2-monthly consolidation sessions. It aimed to educate parents and train
      them in adapted communication tailored to their child's individual competencies.
      Twenty-eight children with autism were randomised between this treatment and
      routine care alone, stratified for age and baseline severity. Outcome was
      measured at 12 months from commencement of intervention, using standardised
      instruments. RESULTS: All cases studied met full Autism Diagnostic Interview
      (ADI) criteria for classical autism. Treatment and controls had similar routine
      care during the study period and there were no study dropouts after treatment had
      started. The active treatment group showed significant improvement compared with
      controls on the primary outcome measure--Autism Diagnostic Observation Schedule
      (ADOS) total score, particularly in reciprocal social interaction--and on
      secondary measures of expressive language, communicative initiation and parent
      child interaction. Suggestive but non-significant results were found in Vineland
      Adaptive Behaviour Scales (Communication Sub-domain) and ADOS stereotyped and
      restricted behaviour domain. CONCLUSIONS: A Randomised Treatment Trial design of
      this kind in classical autism is feasible and acceptable to patients. This pilot
      study suggests significant additional treatment benefits following a targeted
      (but relatively non-intensive) dyadic social communication treatment, when
      compared with routine care. The study needs replication on larger and independent
      samples. It should encourage further RCT designs in this area.

PMID- 15482503
TI  - Using self-report to identify the broad phenotype in parents of children with
      autistic spectrum disorders: a study using the Autism-Spectrum Quotient.
AB  - BACKGROUND: The concept of the 'broad phenotype' of autism refers to the finding
      that relatives of people with autism often have mild forms of autistic-like
      characteristics, such as social and communicative difficulties. This study used
      the Autism Spectrum Quotient (AQ), a questionnaire devised to assess features of
      the broad phenotype in adults, with parents of people with autism, to see whether
      they would be more likely to obtain extreme scores than a control group. METHODS:
      The AQ was administered to parents of 69 people with an autism spectrum disorder
      and parents of 52 controls. RESULTS: On two of the five subscales of the AQ,
      social skills and communication, parents of people with autism obtained higher
      scores than control parents. The other three scales, attention to detail,
      attention switching, and imagination, did not differentiate groups. The
      correlation between social skills and communication scales was .663. The scales
      can be combined to give an index of broad phenotype. CONCLUSIONS: The AQ appears
      to be sensitive to the broad phenotype, provided attention is restricted to the
      social skills and communication scales.

PMID- 15482504
TI  - Can the Children's Communication Checklist differentiate between children with
      autism, children with ADHD, and normal controls?
AB  - BACKGROUND: The Children's Communication Checklist (CCC; Bishop, 1998) is a
      questionnaire that was developed to measure pragmatic language use and may be
      completed by parents and teachers. Two studies are reported, which were designed
      to investigate: (1) whether children with Attention Deficit Hyperactivity
      Disorder (ADHD) encounter pragmatic language problems in comparison with normal
      controls (NC), (2) whether children with ADHD and children with High Functioning
      Autism (HFA) can be differentiated using the CCC, (3) the usefulness of the CCC
      for parents and teachers in a clinical and in a research setting, and (4) the
      role of age in pragmatic language use in ADHD and HFA. METHOD: In the first study
      (clinical sample) 50 children with ADHD, 50 children with HFA, and 50 NC were
      compared to each other using the CCC. In the second study (research sample) CCC
      data was gathered on 23 children with ADHD (without co-morbid disorders), 42
      children with HFA, and 35 NC. RESULTS: Compared to NC, children with HFA showed
      pragmatic deficits on all CCC scales. Children with ADHD demonstrated deficits
      compared to NC as well. Moreover, the ADHD and HFA groups differed from each
      other on most of the scales. Discriminant analyses showed that CCC scales were
      relevant for case identification in these samples. Furthermore, profiles of
      impairment seen in children with HFA and ADHD did not vary with age. CONCLUSION:
      Pragmatic difficulties do occur in both HFA and ADHD. The present studies
      indicate that the CCC is a useful instrument to obtain information concerning
      pragmatic language use in both a clinical and a research setting. Although the
      information of parents is more tightly linked to the diagnosis, combining the
      information of both parent and teacher slightly improves case identification.

PMID- 15482505
TI  - Associations among adolescent risk behaviours and self-esteem in six domains.
AB  - BACKGROUND: This study investigated associations among adolescents' self-esteem
      in 6 domains (peers, school, family, sports/athletics, body image and global self
      worth) and risk behaviours related to substance use, bullying, suicidality and
      sexuality. METHOD: A multistage stratified sampling strategy was used to select a
      representative sample of 939 English-, Afrikaans- and Xhosa-speaking students in
      Grades 8 and 11 at public high schools in Cape Town, South Africa. Participants
      completed the multidimensional Self-Esteem Questionnaire (SEQ; DuBois, Felner,
      Brand, Phillips, & Lease, 1996) and a self-report questionnaire containing items
      about demographic characteristics and participation in a range of risk
      behaviours. It included questions about their use of tobacco, alcohol, cannabis,
      solvents and other substances, bullying, suicidal ideation and attempts, and
      risky sexual behaviour. Data was analysed using a series of logistic regression
      models, with the estimation of model parameters being done through generalised
      estimation equations. RESULTS: Scores on each self-esteem scale were
      significantly associated with at least one risk behaviour in male and female
      adolescents after controlling for the sampling strategy, grade and race. However,
      specific self-esteem domains were differentially related to particular risk
      behaviours. After taking the correlations between the self-esteem scales into
      account, low self-esteem in the family and school contexts and high self-esteem
      in the peer domain were significantly independently associated with multiple risk
      behaviours in adolescents of both sexes. Low body-image self-esteem and global
      self-worth were also uniquely associated with risk behaviours in girls, but not
      in boys. CONCLUSIONS: Overall, the findings suggest that interventions that aim
      to protect adolescents from engaging in risk behaviours by increasing their self
      esteem are likely to be most effective and cost-efficient if they are aimed at
      the family and school domains.

PMID- 15482512
TI  - Cough, wheezing and asthma in children: lesson from the past.
AB  - Recurrent cough is an important medical and sometimes frustrating problem
      encountered by pediatricians, especially if it is not associated with wheeze or
      other evidence of systemic disease. In the past, many children with chronic cough
      have been diagnosed as asthmatic. However, epidemiological, clinical and
      laboratory studies conducted over the last ten years elucidated many aspects of
      the relationship between cough and bronchoconstriction. It is difficult to make a
      diagnosis of asthma on cough alone, but the setting in which the patient is seen
      (i.e., in a primary care setting or ain a specialistic clinic) may address
      doctors to the right diagnosis. A prudent ''wait and see'' approach may be useful
      in many occasions.

PMID- 15482513
TI  - Coughing in pre-school children in general practice: when are RAST's for
      inhalation allergy indicated?
AB  - To identify patterns of clinical history associated with extreme (high or low)
      probabilities of allergic sensitization in coughing children so as to restrict
      allergy testing to those with an intermediate probability of sensitization. A
      total of 752 children, aged 1-4, visiting their GPs for coughing (>or=5 days),
      were tested for IgE-antibodies to house dust mite, cat and dog
      [RadioAllergoSorbent Test (RAST)]. Parents completed a questionnaire on family
      history of atopy, breastfeeding, smoking, pets, and floor covering. Data of 640
      children could be analyzed, 83 (13%) were IgE-positive. In a logistic regression
      analysis, a scoring formula for the prediction of being IgE-positive was
      constructed using variables from the patient's history. Significant contributors
      for sensitization were: age (3-4 yr), infantile eczema, positive family history
      of mite-allergy, sibling(s) with pollen-allergy, and smoking by parents. If only
      one of these characteristics is present, the probability of sensitization is <
      25%. In such cases watchful waiting may be preferred over allergy testing. In
      other cases, a negative RAST may help to exclude sensitization, whereas a
      positive RAST helps to establish the diagnosis. Thus, acting on clinical history
      alone may save approximately 80% of RAST's. Patient history-derived information
      contributes to distinguishing children who are at low risk for sensitization to
      house dust mite, cat, and dog. The scoring formula may help GPs to identify
      children with a low probability of being sensitized. This may form the basis for
      watchful waiting. In others, allergy testing may be useful to gain more
      diagnostic certainty.

PMID- 15482514
TI  - Influence of MMR-vaccinations and diseases on atopic sensitization and allergic
      symptoms in Swiss schoolchildren.
AB  - The prevalence of asthma and allergic disease has increased in many countries. It
      has been proposed that vaccinations may contribute to the development of allergic
      disease by reducing clinical infections in infancy or through the direct IgE
      inducing effects of the vaccines. Evidence for a potential role of immunizations
      in the development of allergic disease is scarce. Therefore the objective was to
      study the associations between vaccinations against measles, mumps and rubella
      (MMR), natural infections of these diseases and atopic sensitization to indoor
      and outdoor allergens and allergic symptoms in schoolchildren. The cross
      sectional study including 1537 8(th) grade school children aged 13-15 years
      living in 10 communities across Switzerland was organized in the framework of an
      environmental health surveillance program within the School Health Services
      (Swiss Surveillance Program of Childhood Asthma and Allergies with respect to Air
      Pollution and Climate, SCARPOL). Main outcome measures were asthma and sneezing
      during pollen season assessed by parental questionnaires and atopic sensitization
      determined by IgE concentrations to various allergens. It was found that parents'
      reported history of measles or mumps was associated with a stronger immune
      response than two or more vaccinations against the respective infection (measles:
      geometric mean IgG titers (GMT) lU/ml (95% Cl) 2.8 (2.0-3.9) vs. 1.2 (1.0-1.4),
      mumps: GMT PE/ml (95% Cl) 16.3 (13.9-19.1) vs. 8.5 (6.1-11.7). With respect to
      atopic sensitization similar associations for exposure by natural MMR-infections
      or MMR-vaccinations were found: measles: OR (95% Cl) 1.02 (0.53-1.96) vs. 1.22
      (0.69-2.16), mumps: 0.59 (0.38-0.93) vs. 0.79 (0.49-1.27), rubella: 0.93 (0.61
      1.43) vs. 0.95 (0.66-1.37), respectively. Inverse relationships were found
      between the risk of asthma and a positive disease history or vaccination of
      measles 0.36 (0.14-0.91) vs. 0.45 (0.21-0.98) or a positive serum titer against
      measles 0.65 (0.35-1.20). From the present study can be concluded that exposure
      by MMR-vaccinations or natural MMR-infections in childhood does not increase the
      risk of sensitization to common allergens as well as to allergic respiratory
      diseases. MMR-vaccinations or natural MMR-infections are therefore an unlikely
      factor contributing to the increase in atopic disease in developed countries.

PMID- 15482515
TI  - BCG vaccine modulates intestinal and systemic response to beta-lactoglobulin.
AB  - Beta-Lactoglobulin (BLG) is a clinically important antigen in cow's milk and one
      of the major allergens causing cow's milk allergy. Bacillus Calmette-Guerin (BCG)
      vaccination has been suggested to modify immune response possibly decreasing the
      risk of allergy to some antigens in both human and experimental animals. In the
      present study, we have analyzed whether the early BCG vaccination has any effect
      on the markers of systemic and gastrointestinal (GI) sensitization to BLG. We
      immunized two groups of Hooded-Lister rat puppets with intraperitoneal injections
      of native BLG at 43 and 62 days with pertussis vaccine as adjuvant, one group
      receiving additionally BCG. The animals were then fed native and denatured milk
      products twice weekly from 73 to 131 days of age, when they were killed. Control
      group was not vaccinated and received normal rat forage. Total immunoglobulin E
      (IgE) levels and BLG-specific IgG(1) and IgG(2a) concentrations were determined
      in serum samples. Spontaneous interleukin (IL)-4 and interferon (IFN)-gamma
      production from duodenal specimens were measured, and the inflammatory cells were
      quantitated in specimens from different sections of the GI tract. Administration
      of BCG simultaneously with BLG resulted in reduced IgE concentration in serum,
      while the specific IgG(1) and IgG(2a) antibody responses and the spontaneous
      secretion of IL-4 and IFN-gamma were not affected. Furthermore, BCG-induced
      eosinophilic infiltration and increase of intraepithelial lymphocytes (IEL) in
      the GI mucosa, and a trend toward increased number of lamina propria mononuclear
      inflammatory cells in the colon (BCG compared with BLG, p = 0.09; BCG compared
      with controls, p = 0.02). Controls showed increment of IgG(1) response in
      comparison with the BLG group (p = 0.04) and increase of mucosal eosinophilic
      infiltration. The BCG modified the response to BLG both at the systemic level as
      shown by decrease of total IgE and at GI mucosa where increase of eosinophilic
      infiltration and increased number of IEL were seen. Increment of IgG(1) level and
      eosinophils in the controls might be related with the lack of modulatory effect
      of pertussis vaccination. A shift of response toward the lower GI tract after BCG
      immunization as shown by a trend for increase of mononuclear inflammatory cells
      in colon lamina propria mimics disease development in some cases of clinical food
      allergy, and emphasizes the need for evaluation of the changes in the whole GI
      tract in food allergy models.

PMID- 15482516
TI  - Effect of BCG vaccination in asthmatic schoolchildren.
AB  - Recent studies have explored the effect of Bacilli Calmette-Guerin (BCG) or
      Mycobacterium vaccae vaccination in asthmatic patients, yielding conflicting
      results. We investigated the effect of BCG vaccination in asthmatic
      schoolchildren, especially focusing on the cytokine pattern released by
      mononuclear cells. After a 1-yr run-in period, 67 asthmatic schoolchildren
      received intradermal immunization with BCG (33 patients) or placebo (34
      patients). Both groups were followed during 1 yr. Serum immunoglobulin E (IgE)
      levels did not change after BCG (407.1 +/- 86.6 vs. 415.1 +/- 86.7 IU/ml, mean +/
      s.e.m.), but increased after placebo (406.7 +/- 67.0 vs. 619.7 +/- 90.7 IU/ml, p
      = 0.001) administration. Interleukin (IL)-4 and interferon (IFN)-gamma measured
      in the supernatant of stimulated cultured blood mononuclear cells did not change
      in the BCG group (10.8 +/- 2.3 vs. 17.9 +/- 5.7 pg/ml, and 348.6 +/- 118.0 vs.
      354.8 +/- 139.0 pg/ml, respectively), while in the control group IL-4 increased
      (from 6.7 +/- 1.3 to 16.1 +/- 6.0 pg/ml, p < 0.05), and IFN-gamma decreased (from
      279.9 +/- 82.1 to 232.1 +/- 109.6 pg/ml, p = 0.01). In comparison with their
      initial status, most patients maintained the same asthma severity and the same
      proportion of emergency room visits at the end of the study. The proportion of
      those in whom asthma improved or worsened was the same in both groups. We
      concluded that, contrary to the common hypothesis, BCG vaccination in asthmatic
      children was unable to cause a long-term reinforcement of Th(1) response,
      although it could avoid the increased Th(2) response observed in control
      patients.

PMID- 15482517
TI  - Food allergy and atopic dermatitis in infancy: an epidemiologic study.
AB  - Atopic dermatitis is common in infancy. The role of food allergy in atopic
      dermatitis of infancy is unclear. We examined the relationship between atopic
      dermatitis and immunoglobulin E (IgE)-mediated food allergy in infancy. A birth
      cohort of 620 infants with a family history of eczema, asthma, hayfever or
      immediate food allergy in a parent or sibling: 487 children had complete data
      including skin prick tests (SPTs) to evaluate IgE-mediated food allergy to cow
      milk, egg and peanut. Participants were grouped as no atopic dermatitis (Gp 0) or
      in quartiles of increasing severity of atopic dermatitis (Gps 1-4) quantified by
      days of topical steroid use as reported monthly. Adverse reactions to foods were
      recorded. The cumulative prevalence of atopic dermatitis was 28.9% to 12 months
      (10.3% of the cohort of moderate severity). As atopic dermatitis severity
      increased so did the prevalence of IgE-mediated food allergy (Gp 0, 40/346 vs. Gp
      1, 6/36 vs. Gp 2, 8/35 vs. Gp 3, 12/35 vs. Gp 4, 24/35; chi(2) = 76; p < 10(-6)),
      and the frequency of reported adverse food allergy reactions (Gp 0, 43/346 vs. Gp
      1, 4/36 vs. Gp 2, 8/35, vs. Gp 3, 5/35, vs. Gp 4, 13/35; chi(2) = 17; p = 0.002).
      The relative risk of an infant with atopic dermatitis having IgE-mediated food
      allergy is 5.9 for the most severely affected group. Atopic dermatitis is common
      in infancy. There is a strong association between IgE-mediated food allergy and
      atopic dermatitis in this age group.

PMID- 15482518
TI  - An evaluation of the diagnostic value of different skin tests with egg in
      clinically egg-allergic children having atopic dermatitis.
AB  - Skin testing is a common diagnostic procedure in food allergy, but the final
      diagnosis of food allergy is based on the clinical response to food challenge. We
      studied the value of the skin prick-prick test (SPT), skin application food test
      (SAFT) and atopy patch test (APT) with fresh egg extract in diagnosing egg
      allergy. Ten clinically egg-allergic children with atopic dermatitis (AD; age 10
      months to 8.4 yr, mean 3.4 yr) and 10 egg-tolerant children with and 10 without
      AD (age 2.4-11 yr, mean 5.5 yr) participated. In SAFT several false-negative
      reactions were seen, whereas all clinically egg-allergic children were positive
      in SPT and 40-60% in APT. In APT and in SPT false-positive reactions to egg were
      observed. In this study comprising a small number of patients including control
      subjects, neither SAFT nor APT with fresh whole egg extract were able to increase
      the diagnostic accuracy in detecting egg-allergic children with AD compared with
      SPT.

PMID- 15482519
TI  - The diagnostic value of skin prick testing in children with food allergy.
AB  - The diagnostic accuracy of the skin prick test (SPT) in food allergy is
      controversial. We have developed diagnostic cut-off levels for SPT in children
      with allergy to cow milk, egg and peanut. Based on 555 open food challenges in
      467 children (median age 3.0 yr) we defined food-specific SPT weal diameters that
      were '100% diagnostic' for allergy to cow milk (>or=8 mm), egg (>or=7 mm) and
      peanut (>or=8 mm). In children < 2 yr of age, the corresponding weal diameters
      were >or=6 mm, >or=5 mm and >or=4 mm, respectively. These SPT cut-off levels were
      prospectively validated in 90 consecutive children <or=2 yr with challenge-proven
      food allergy. In young infants under 6 months of age who have not previously been
      exposed to a particular food item, the SPT were often negative or below the
      diagnostic cut-off but reached the diagnostic cut-off at the time of challenge in
      the second year of life. We assessed the diagnostic agreement between food
      specific immunoglobulin E (IgE) antibody levels and SPT in a cohort of 820
      infants and children under 2 yr of age (median age 13.1 months) with suspected
      allergy to cow milk, egg or peanut. When applying published 95%-positive
      predictive CAP values, the diagnostic accuracy of SPT and IgE antibody levels was
      similar for cow milk, but SPT was more sensitive in diagnosing allergy to egg (p
      < 0.0001) and peanut (p < 0.0001). Further studies are required to define age
      specific diagnostic IgE antibody and SPT cut-off levels use in infants under 2 yr
      of age with suspected food allergies.

PMID- 15482520
TI  - Specific immunoglobulin E antibodies to peanut over time in relation to peanut
      intake, symptoms and age.
AB  - The clinical outcome of peanut allergy and some factors associated with
      development of peanut allergy remain unsolved. It has not been clarified to what
      extent peanut intake affects immunoglobulin (IgE) antibody formation in peanut
      sensitized individuals. The aim of the study was to investigate the development
      of peanut hypersensitivity in children and adolescents with specific IgE
      antibodies to peanut, using questionnaires and current serum tests and comparing
      it to information obtained 5-6 yr earlier, to investigate how peanut intake
      during this period related to subject age, IgE antibody levels and symptoms and
      to investigate what information this patient group was given at the time of
      diagnosis regarding avoidance of peanut related food. All patients with
      detectable peanut-specific IgE antibodies investigated during 1994-1996 deriving
      from two allergy laboratories in the western region of Sweden were traced and
      reinvestigated (n=132). A total of 111 subjects (63 with peanut allergy and 48
      peanut sensitized) participated in the questionnaire. Eighty-six of them
      consented to be enrolled in a further interview and renewed testing of specific
      IgE antibody to peanut 5 yr later. All tests were done using the Pharmacia CAP
      system. Increased IgE antibody levels during follow-up was related to age;
      subjects 0-6 yr at initial test occasion were more likely to have higher IgE
      antibody class than the older individuals (p=0.018). Exposure to peanut during
      the study, i.e. 5-6 yr since diagnosis, did not seem to affect the result. During
      the follow-up period, 29 out of 86 (34%) increased their IgE antibody class. At
      the second test occasion the remaining subjects had similar (28%) or lowered
      (38%) levels of IgE antibodies. Exposure to peanut during follow-up was more
      common in subjects with IgE antibody class 1-3 compared to subjects with high
      value (> 3) at the initial test (p=0.003). Reported symptoms during follow-up
      were also more common in subjects with initially high IgE antibody value.
      Individuals with initially high IgE antibodies to peanut had been given more
      information about peanut allergy and cross-reacting allergens than other
      individuals. The subjects over 6 yr of age showed a decrease in peanut-specific
      IgE class over a 5-yr period. Together with the literature, our result suggest
      that follow-up and renewed testing is recommended, since there may be a change in
      IgE antibody classes and clinical sensitivity over time. Even in Sweden, with a
      low consumption of peanuts, the youngest individuals with peanut sensitization
      experienced a similar course of events that has been reported in other countries.

PMID- 15482521
TI  - General paediatricians and the case of resolving peanut allergy.
AB  - Children with peanut allergy are almost always advised to avoid nuts for life.
      There have been recent reports from academic centres that in some cases the
      allergy might resolve and thus these dietary restrictions can be lifted. To
      evaluate resolution of peanut allergy in a selected group of children in a
      general paediatric setting. Children 4-16 yr old with a clear history of an
      allergic reaction to peanuts who had not had any reaction in the previous 2 yr
      were eligible. Specific immunoglobulin E (IgE) or skin prick test (SPT) at the
      time of diagnosis was sought. A SPT and specific IgE was then done and if this
      was <or= 8 mm and <or= 17.5 kU[A]/l respectively, a double-blind placebo
      controlled food challenge was undertaken. A negative challenge consisted of
      tolerance to a cumulative dose of 15.8 g peanuts followed by an open challenge.
      From the 82 case notes reviewed 54 children were eligible to participate. Twenty
      nine agreed to participate and underwent SPT (29) and specific IgE (28). Of these
      children eight were eligible for food challenge. Four challenges were negative
      and four positive. Peanut allergy may resolve in approximately 15% of selected
      children attending an allergy clinic run by general paediatricians in a district
      general hospital. Food challenge constitutes the appropriate way of removing the
      burden that comes with a diagnosis of peanut allergy and enables dietary
      restriction to cease.

PMID- 15482522
TI  - Tolerance of heat-treated kiwi by children with kiwifruit allergy.
AB  - Kiwifruit allergy is increasing among children but whether heating affects
      clinical tolerance to kiwifruit is unknown. To assess tolerance to heated
      kiwifruit in children allergic to fresh kiwifruit. In this prospective trial, 20
      children (median age 9.4 yr) with a history of immediate allergic reactions to
      fresh kiwifruit underwent double-blind placebo-controlled food challenges with
      steam-cooked (100 degrees C for 5') and industrially homogenised kiwifruit. Skin
      prick tests with a commercial kiwifruit allergen, raw kiwifruit and double-blind
      placebo-controlled food challenge with 25 g of fresh kiwifruit were used to
      confirm the history. Specific kiwifruit IgE to native and homogenized fruit were
      identified by immunoblotting. Fresh kiwifruit induced positive skin prick wheals
      in all children (confirmed during challenge in 19 patients). Commercial skin
      prick test elicited a positive response in five children, steam-cooked kiwifruit
      in five, and the homogenised kiwifruit preparation in none. UniCAP determinations
      were positive for kiwifruit in three patients. All children's sera showed
      specific IgE at immunoblotting with raw kiwifruit and one with the homogenised
      preparation (major allergens identified: Act c 1 and Act c 2). There was no
      clinical reactivity following challenge with homogenised kiwifruit but one child
      reacted to cooked kiwifruit challenge. Industrial heat treatment and
      homogenisation can make kiwifruit safe for children who are allergic to this
      increasingly popular fruit. This has dietary implications for children who are
      allergic to several fruit and vegetable proteins.

PMID- 15482523
TI  - Dermatophagoides-induced interleukin-10 production by peripheral blood
      lymphocytes from patients with asthma in remission.
AB  - Interleukin (IL)-10 is a cytokine that regulates inflammatory responses. We
      studied the role of IL-10 in the development of tolerance to Dermatophagoides
      farinae in asthma patients in remission, since asthma improves in most children
      during adolescence. The spontaneous production of IL-10 by cultured peripheral
      blood mononuclear cells (PBMC) was higher in patients with active asthma than in
      normal subjects. IL-10 production decreased when 1 microg/ml D. farinae was added
      to cultures, but increased again in a dose-dependent manner when higher
      concentrations of D. farinae were added. In patients with remission of asthma, IL
      10 production was lower than in patients with active asthma. However, production
      of IL-10 showed a reciprocal increase in the presence of 1 microg/ml D. farinae,
      and decreased again at 10 and 50 microg/ml D. farinae. Such alterations were not
      observed in normal subjects. Cell lines established from patients asthma in
      remission showed higher IL-10 production when compared with that by cell lines
      from normal subjects or patients with active asthma when the cells were
      stimulated by D. farinae at 1 or 10 microg/ml. Neutralization of IL-10 led to
      revival of the D. farinae-specific proliferative response of PBMC from patients
      in remission, which was otherwise decreased. The increase of IL-10 production
      stimulated by D. farinae was inhibited by addition of an anti-IL-10 antibody. In
      contrast, antigen-induced interferon (IFN)-gamma production, which was increased
      by D. farinae stimulation when patients were in remission, did not increase after
      treatment with anti-IL-10, although spontaneous IFN-gamma production increased to
      the level seen after D. farinae stimulation. The reduced IL-4 production by cells
      from patients in remission after stimulation with D. farinae antigen, which was
      significantly higher in active patients, was not reversed by neutralization of IL
      10. The D. farinae-induced IL-10/IL-4 production ratio, but not the IL-10/IL-5
      production ratio, may be a significant indicator for evaluation of whether a
      patient has been in remission. In conclusion, D. farinae-specific anergy of T
      cells is likely to be induced by increased levels of IL-10 and IFN-gamma that are
      initially produced by specific T cells after exposure to relevant mite allergen
      in patients in remission.

PMID- 15482524
TI  - The occurrence of mite-containing wheat flour.
AB  - Anaphylaxis after eating mite-infested wheat flour has been recently reported.
      This paper is to describe two cases and examine the occurrence of mite
      contamination in wheat flour in Japan. Packages of wheat flour from retail
      outlets and homes were examined microscopically for the presence of mites. Three
      of 176 packages from retail outlets and seven of 127 from homes were infested
      with mites, and it seems likely that the mite contamination takes place in most
      cases at homes after the packages have been opened. No mites were found in
      packages stored in a refrigerator, therefore, mite-sensitive patients must be
      advised to store wheat flour products in a refrigerator.

PMID- 15482525
TI  - Montelukast and airway remodeling in children with chronic persistent asthma: an
      open study.
AB  - We report a 4 yr follow up study of seven asthmatic children with chronic
      persistent asthma, high-residual volume and low-density areas at high-resolution
      computerized tomography after treatment with salmeterol and fluticasone.
      Improvement of lung function with disappearance of low-density areas in six
      patients after treatment with fluticasone and montelukast was obtained.

PMID- 15482526
TI  - Antimicrobial susceptibility of skin-colonizing S. aureus strains in children
      with atopic dermatitis.
AB  - Children with atopic dermatitis (AD) are prone to recurrent cutaneous and
      occasional systemic infections caused by Staphylococcus aureus. Antibiotic
      therapy represents an important component of the overall management of AD,
      especially during exacerbations of disease. Erythromycin is still widely used as
      a first-line antibiotic for this indication. We studied 115 consecutive children
      (mean age: 2.7 yr, range: 0.2-15) with moderate to severe AD (mean SCORAD: 43.2,
      range: 16-77) presenting to our outpatient department. Staphylococcus aureus was
      isolated from 100 of 115 (87%). Antimicrobial susceptibility testing revealed
      resistance against erythromycin in 18 and against roxithromycin in 19%,
      respectively. Six percentage of the strains were resistant or only intermediately
      susceptible to fusidic acid, 13% to amoxicillin and 1% to clindamycin. All
      strains isolated were susceptible to oxacillin, amoxicillin/clavulanic acid,
      cefadroxil and cefuroxim. The high rate of primary resistance to macrolides
      should be born in mind when starting antibiotic therapy in children with AD.
      Since Gram-positive cocci represent the only relevant microbial agents in AD,
      first generation cephalosporins such as cefadroxil, whose antimicrobial spectrum
      is basically restricted to Gram-positive bacteria, would appear to be the ideal
      first-line antibiotics for the treatment of bacterial superinfections.

PMID- 15482527
TI  - Many staging systems for hepatocellular carcinoma: evolution from Child-Pugh,
      Okuda to SLiDe.

PMID- 15482528
TI  - Management of hepatitis C virus genotype 4.
AB  - Hepatitis C virus (HCV) genotype 4 is predominantly found in the Middle East and
      North Africa. Because most of the large randomized controlled trials of antiviral
      therapy for chronic hepatitis C were conducted in North America and Europe,
      little is known about management of patients with this particular genotype. Based
      on the available data, sustained virological response rates to interferon-based
      therapies appear to be intermediate between the relatively resistant HCV genotype
      1 and the readily responsive genotypes 2 and 3. Several large prospective studies
      of pegylated interferon plus ribavirin combination therapy, the current gold
      standard treatment, have recently been completed and will be reviewed.

PMID- 15482529
TI  - Gastrointestinal luminal tuberculosis: establishing the diagnosis.
AB  - BACKGROUND AND AIM: To study the profile of gastrointestinal luminal tuberculosis
      (GITB) patients who have been treated on a confirmed and a presumptive diagnosis.
      METHODS: A total of 260 patients who had an initial diagnosis of GITB were
      included in this retrospective analysis. Clinical, radiologic, endoscopic,
      histopathologic and microbiologic features of these patients were studied in
      detail. RESULTS: GITB was confirmed in 66.5% patients (cGITB), while 29.5% had
      presumed GITB (pGITB). In 3.9% patients, Crohn's disease (CD) was misdiagnosed
      initially as GITB. There was no significant difference in the clinical and
      radiologic features except a higher incidence of a radiologically abnormal
      ileocecal region in cGITB patients. Endoscopic biopsies from ulcerated masses and
      ulcers had the highest yield of confirmation (100% and 68%, respectively) when
      subjected to histopathology, acid-fast bacilli smear and culture studies.
      Confirmed diagnosis was obtained in 100% of cases occurring in the upper
      gastrointestinal tract, 66% of cases in the ileocecal region/colon and 40% of
      cases that had small bowel involvement. In 21% of cases, extraluminal sites
      helped to confirm the diagnosis. As the presence of diarrhea, bleeding, fistulae,
      perianal disease and extraintestinal manifestations favored a diagnosis of CD,
      the presence of these features initially or on subsequent follow up helped to
      minimize the misdiagnosis of GITB. CONCLUSIONS: As a differential diagnosis, CD
      must be ruled out before starting treatment for GITB. In our study, an intense
      search for histologic and microbiologic proof of the presence of TB from luminal
      and extraluminal sites established the diagnosis in 66.5% of cases. Surgery for
      establishing the diagnosis should be reserved for complicated cases.

PMID- 15482530
TI  - Severe ulcerative colitis: prospective study of parameters determining outcome.
AB  - BACKGROUND: One-third of patients with exacerbations of ulcerative colitis (UC)
      require colectomy and 1% die. Although several studies have reported parameters
      associated with failure of medical treatment, studies using multivariate analysis
      of various predictors are scanty. METHODS: Demographic, clinical and laboratory
      parameters within 48 h of admission of 50 consecutive patients (55 episodes) were
      prospectively recorded. Each episode was treated with intravenous hydrocortisone,
      antibiotics and fluid administration. The data of patients who failed to respond,
      deteriorated, developed complications requiring emergency surgery or died within
      7 days of hospitalization, were compared with the data of those who responded
      during this period using Mann-Whitney U-test or chi-squared tests. Variables
      found to be significant on univariate analysis were entered into a multivariate
      model. RESULTS: Medical treatment failed in 10 of 55 episodes; eight had surgery
      (one died), another died with bowel perforation and peritonitis and one left
      hospital in a moribund state. Younger age, pedal edema, transverse colonic
      diameter >5 cm on abdominal radiograph, low hemoglobin, low serum albumin, high C
      reactive protein, presence of fibrin degradation product (FDP) in serum, low
      serum fibrinogen, prolonged prothrombin time, Truelove-Witt's fulminant disease,
      and high clinical activity index were associated with failure of medical
      treatment on univariate analysis. All the above variables were significant by
      multivariate analysis except age, serum albumin level and presence of FDP.
      CONCLUSION: It may be possible to predict the failure of medical treatment in
      exacerbations of UC using a scoring system based on clinical parameters and
      simple laboratory tests.

PMID- 15482531
TI  - Frequency of gastropathy and gastric varices in children with extrahepatic portal
      venous obstruction treated with sclerotherapy.
AB  - BACKGROUND: There are limited reports of the effect of endoscopic sclerotherapy
      (EST) on portal hypertensive gastropathy (PHG) and gastric varices (GV) in
      children with extrahepatic portal venous obstruction (EHPVO). We have studied the
      prevalence of PHG and GV in children with EHPVO and assessed the effect of EST on
      them on long-term follow-up. METHODS: From January 1992 to June 2002, consecutive
      children presenting with variceal bleeding due to EHPVO were included in this
      study. All children underwent EST at presentation and at 2-3 week intervals
      thereafter. During each session of endoscopy, gastric mucosa and fundus of the
      stomach was screened carefully to detect PHG and GV. Gastric varices were
      classified as gastroesophageal (GOV) and isolated gastric varices (IGV). RESULTS:
      In total, 274 cases of EHPVO were managed during the study period. The mean age
      was 7.4 +/- 3.5 years with a male to female ratio of 2.3:1. Of these 274 cases,
      186 completed the EST program (study population), 60 were lost to follow-up, five
      died and 23 underwent surgery. At presentation (n = 274) 27% cases had PHG (3.6%
      severe) and 68.6% had GV (GOV 66.8%, IGV 1.8%). Following EST (n = 186) there was
      a significant (P < 0.001) decrease in GOV (45% from 64%) but an increase in IGV
      (14% from 1%) and PHG (51.6% from 24.7%). There was also a significant increase
      in severe PHG (15.6% from 3.2%, P < 0.05). On follow-up (mean follow-up 38 +/- 30
      months) 19% children with IGV bled while none with PHG bled. CONCLUSIONS: Portal
      hypertensive gastropathy and gastric varices are quite common in children with
      EHPVO. Following EST, there is a chance of developing isolated gastric varices.

PMID- 15482532
TI  - Antralization of gastric incisura is topographically associated with increased
      gastric epithelial apoptosis and proliferation, but not with CagA seropositivity.
AB  - BACKGROUND AND AIMS: Helicobacter pylori infection is linked with increased
      antralization at the gastric incisura. The present study aimed to determine if
      antralization is associated with altered gastric epithelial apoptosis and
      proliferation and with seropositivity of the cytotoxin-associated gene product A
      (CagA) of H. pylori. METHODS: Gastric biopsies taken from the antrum, incisura,
      body and fundus of 75 patients (34 male, 41 female; mean age 59.5 years) were
      used for diagnosis of H. pylori infection and assessments of histological
      changes. Apoptosis and Ki-67 expression in epithelial cells were determined for
      the antral, incisura and body biopsies by immunohistochemistry. Serum samples
      were tested by enzyme-linked immunosorbent assays for anti-H. pylori and anti
      CagA IgG antibodies. RESULTS: Apoptotic index (AI) and Ki-67 proliferation index
      (PI) were greater in the presence (vs absence) of H. pylori infection at the
      antrum, incisura and body (all P < 0.001), and topographically associated with
      chronic gastritis and gastric atrophy/intestinal metaplasia at the antrum and
      incisura (all P < 0.001). Moreover, AI and PI were greater in the presence (vs
      absence) of antralization at the incisura (20.2 +/- 0.9 vs 11.4 +/- 0.1.1 and
      48.9 +/- 2.5 vs 29.9 +/- 2.5, both P < 0.001). CagA seroprevalence was 41% in the
      39 infected patients. CagA seropositivity was associated with gastric
      atrophy/intestinal metaplasia at the antrum (chi(2) = 4.67, P = 0.03) and
      incisura (chi(2) = 4.88, P = 0.03), but not associated with gastric epithelial
      apoptosis and Ki-67 expression, nor with antralization at the incisura.
      CONCLUSIONS: Antralization of gastric incisura is topographically associated with
      increased gastric epithelial apoptosis and proliferation, but not with CagA
      seropositivity.

PMID- 15482533
TI  - Gene expression analysis in the stomachs of water immersion-restraint stress rats
      using high-density oligonucleotide array.
AB  - BACKGROUND AND AIM: Research on gastric lesions developing in response to stress
      is essential to elucidating the pathogenesis of these lesions as well as the
      interplay with other factors, including Helicobacter pylori infection and non
      steroidal anti-inflammatory drug use. Genes expressed individually or in sets,
      such as heat shock proteins, growth factors, proto-oncogenes and cyclooxygenases,
      have been investigated in the stomach. However, gene expression in the stomach
      after stress exposure have not yet been comprehensively examined. We investigated
      the gastric gene expression profile in response to stress. METHODS: A high
      density oligonucleotide array, representing approximately 850 genes, was used to
      determine gene expression changes in the stomachs of water immersion-restraint
      stress (WIRS) rats. RESULTS: Fifty-eight genes including expressed sequence tag
      (EST) genes were upregulated more than twofold in the 30 min-WIRS rat stomach as
      compared with the control. Concomitantly, five genes were downregulated. Numbers
      of up- or downregulated genes decreased rapidly at 1 and 2 h of WIRS. Altered
      gene expression of heat shock proteins, cell cycle regulators, proto-oncogenes
      and metabolic enzymes were recognized. Several of these genes, including p38
      mitogen-activated protein kinase, did not reportedly show gastric expression
      changes in response to stress. CONCLUSION: These results suggest that, in
      addition to the previously identified stress-induced genes, expression of a
      number of other genes in the stomach is also involved in stress response.

PMID- 15482534
TI  - Normal colon transit time in healthy Chinese adults in Hong Kong.
AB  - BACKGROUND AND AIM: Colon transit study with radio-opaque markers is helpful in
      the evaluation of chronic constipation. Normal reference values, based on radio
      opaque markers, have not been reported from Chinese adults in Hong Kong. METHODS:
      Fifty-one healthy Chinese (27 men, age 42 +/- 12 years) were enrolled through a
      newspaper advertisement. They were requested to fill in detailed dietary records
      and a gastrointestinal symptom questionnaire. Each subject swallowed, under
      supervision, a total of three Sitzmarks capsules, one capsule at the same time on
      each of day 1, 2 and 3. Abdominal films were taken on days 4 and 7, also at the
      same time of the day. Total and segmental transit times were calculated using
      Metcalf's method. RESULTS: The upper limit of normal total colonic transit time
      (CTT) was 62 h, while right, left and rectosigmoid CTT were 16 h, 31 h and 32 h,
      respectively. Women of age 18-35 years had a longer rectosigmoid and total CTT
      compared with their male counterparts (mean total CTT: 39 h vs 18 h, P = 0.05).
      The CTT appeared to be unaffected by the usual dietary components. CONCLUSION: A
      single normal reference value for CTT appeared to be applicable to Chinese adults
      in Hong Kong, irrespective of age, sex and dietary content. However, young
      Chinese women (age 18-35 years) appeared to have longer total and rectosigmoid
      CTT.

PMID- 15482535
TI  - Four years of lamivudine treatment in Chinese patients with chronic hepatitis B.
AB  - BACKGROUND AND AIMS: This study assessed the efficacy and safety of up to 4 years
      of lamivudine treatment and the clinical relevance of the emergence of YMDD
      variant hepatitis B virus (HBV). METHODS: Fifty-eight Chinese adult patients with
      chronic hepatitis B (CHB) were randomized to lamivudine 100 mg/day for up to 5
      years and were monitored for YMDD-variant HBV, hepatitis B e antigen (HBeAg)
      seroconversion (loss of HBeAg and detectable antibody to HBeAg) and serum alanine
      aminotransferase (ALT) concentrations. Four-year data are reported here. RESULTS:
      The rate of HBeAg seroconversion increased with extended therapy and also with
      higher baseline ALT concentrations. YMDD-variant HBV was detected in 67% (39/58)
      of patients at some point during treatment. After 4 years, a total of 47% (27/58)
      of patients achieved HBeAg seroconversion. Thirty-three per cent (13/39) of
      patients with YMDD-variant HBV achieved HBeAg seroconversion; this increased to
      57% (8/14) in patients with moderately elevated (>2-5 x upper limit of normal)
      pre-treatment ALT concentrations. The proportion of patients that achieved normal
      serum ALT increased from 29% (17/58) at baseline to 69% (31/45) following 4 years
      of treatment. That included 68% (23/34) of patients with YMDD-variant HBV and 73%
      (8/11) of those without the variant. All patients receiving lamivudine had
      reduced serum concentrations of HBV-DNA compared with baseline, despite the
      emergence of YMDD-variant HBV in 39 patients. Lamivudine was generally well
      tolerated; there was little change in the number or type of drug-related adverse
      events in the fourth year of the study. CONCLUSIONS: Despite the emergence of
      YMDD-variant HBV, Chinese patients showed increased HBeAg seroconversion and
      improvement in ALT levels with an increased duration of treatment with
      lamivudine.

PMID- 15482536
TI  - Liver cell transplantation leads to repopulation and functional correction in a
      mouse model of Wilson's disease.
AB  - BACKGROUND AND AIM: The toxic milk (tx) mouse is a non-fatal animal model for the
      metabolic liver disorder, Wilson's disease. The tx mouse has a mutated gene for a
      copper-transporting protein, causing early copper accumulation in the liver and
      late accumulation in other tissues. The present study investigated the efficacy
      of liver cell transplantation (LCT) to correct the tx mouse phenotype. METHODS:
      Congenic hepatocytes were isolated and intrasplenically transplanted into 3-4
      month-old tx mice, which were then placed on various copper-loaded diets to
      examine its influence on repopulation by transplanted cells. The control animals
      were age-matched untransplanted tx mice. Liver repopulation was determined by
      comparisons of restriction fragment length polymorphism ratios (DNA and mRNA),
      and copper levels were measured by atomic absorption spectroscopy. RESULTS:
      Repopulation in recipient tx mice was detected in 11 of 25 animals (44%) at 4
      months after LCT. Dietary copper loading (whether given before or after LCT, or
      both) provided no growth advantage for donor cells, with similar repopulation
      incidences in all copper treatment groups. Overall, liver copper levels were
      significantly lower in repopulated animals (538 +/- 68 microg/g, n = 11) compared
      to non-repopulated animals (866 +/- 62 microg/g, n = 14) and untreated controls
      (910 +/- 103 microg/g, n = 6; P < 0.05). This effect was also seen in the kidney
      and spleen. Brain copper levels remained unchanged. CONCLUSION: Transplanted
      liver cells can proliferate and correct a non-fatal metabolic liver disease, with
      some restoration of hepatic copper homeostasis after 4 months leading to reduced
      copper levels in the liver and extrahepatic tissues, but not in the brain.

PMID- 15482537
TI  - Role of polymerase chain reaction and liver biopsy in the evaluation of patients
      with asymptomatic transaminitis: implications in diagnostic approach.
AB  - BACKGROUND AND AIM: Detection of an asymptomatic rise in the hepatic
      aminotransferase (ARHA) value has become a distinct and frequent clinical
      problem. We evaluated a three-step diagnostic algorithm in such patients for
      maximum yield. METHODS: Consecutive patients with an ARHA value 1.5-fold the
      upper limit of normal for at least 4 weeks and who were apparently healthy were
      included in the study. Each patient underwent standard biochemical investigations
      and a stepwise investigative protocol. In the first step, serological markers for
      hepatitis viruses, serum ferritin, 24-h urinary copper, alpha-1-antitrypsin
      phenotyping, and autoimmune markers were carried out. In step two, patients who
      tested negative for all the above markers had polymerase chain reaction (PCR)
      analysis for hepatitis B virus (HBV)-DNA and hepatitis C virus (HCV)-RNA.
      Patients without a diagnosis despite the above investigations underwent a liver
      biopsy as part of step three. RESULTS: Of 105 patients with ARHA, 38 were
      excluded for various reasons and 67 were included for the final analysis. The
      mean age was 35.11 +/- 11.96 years and 56 patients were men. The mean body mass
      index was 24.17 +/- 3.2 kg/m(2). The stepwise diagnostic algorithm achieved a
      diagnosis in 65/67 (97%) patients. Non-alcoholic steatohepatitis (NASH) and
      chronic viral hepatitis were the most common diagnoses, in 24 (36%) patients
      each. Using the diagnostic algorithm a diagnosis was reached in 34% of patients
      with only serological and biochemical investigations, whereas PCR for HBV and HCV
      could further detect the presence of active HBV or HCV viremia in 21% (14/97) and
      a liver biopsy was necessary to establish the diagnosis in 28/67 (42%) patients.
      CONCLUSIONS: A stepwise diagnostic algorithm in patients with ARHA resulted in an
      optimal use of PCR and invasive tests such as liver biopsy. Cryptic HBV and HCV
      infection was frequent among these patients and PCR was necessary in such cases.
      NASH and chronic viral hepatitis were the most frequent causes of ARHA.

PMID- 15482538
TI  - Telomerase reverse transcriptase gene amplification in hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Telomerase activation is essential for the immortality of
      cancer cells. The expression of telomerase reverse transcriptase (hTERT), the
      catalytic component of the telomerase complex, regulates telomerase activity in
      human cancers. Amplification of the hTERT gene, located at chromosome 5p, is
      thought to be a potential genetic event contributing to telomerase activation in
      sporadic tumors. METHODS: The amplification of the hTERT gene was examined in 46
      surgically resected hepatocellular carcinomas (HCC) by real-time polymerase chain
      reaction and the status was compared with the expression of hTERT mRNA and
      clinicopathological parameters. RESULTS: Amplified hTERT genes were found in
      21.7% (10/46) of HCC. The incidence of amplified hTERT genes in poorly
      differentiated HCC (6/12, 50%) was significantly higher than that in highly to
      moderately differentiated HCC (4/34, 11.8%; P = 0.012). Tumor size in those cases
      with hTERT gene amplification was larger compared to those cases with no
      amplification (P = 0.047). Amplification of the hTERT gene was not observed in
      non-cancerous tissues. The hTERT mRNA level did not correlate with the number of
      hTERT genes. CONCLUSIONS: Based on these results, it is thought that hTERT gene
      amplification is a cancer-specific event, and may furthermore contribute to the
      dedifferentiation and development of HCC. However, hTERT gene overexpression was
      rarely due to an increased hTERT gene copy number in HCC.

PMID- 15482539
TI  - Molecular epidemiologic analysis of hepatitis C virus infection in injecting drug
      users with acute hepatitis C in Japan.
AB  - BACKGROUND AND AIM: The aim of this study was to examine whether particular
      hepatitis C virus (HCV) subtypes are spreading among injecting drug users (IDUs)
      in Yamaguchi prefecture, on the south-western tip of the island of Honshu in
      Japan, as found in European countries. METHODS: We prospectively enrolled acute
      hepatitis C patients from January 2001 to March 2003. E2 gene sequences of HCV
      isolates from IDUs with acute hepatitis C were phylogenetically compared to those
      from 30 chronic hepatitis C patients with the same HCV subtypes who had or did
      not have a history of intravenous drug use. RESULTS: Nine of 11 patients (82%)
      with acute hepatitis C were IDUs. The HCV subtypes were 2a in four and 2b in
      five, which contrasted with the high prevalence of subtype 1b in patients with
      chronic liver diseases in Japan. IDUs with acute hepatitis C (22.0 +/- 2.4 years
      old) were significantly younger than those with chronic hepatitis C (49.5 +/- 9.5
      years old) for subtype 2a (P = 0.0005), but not for subtype 2b (25.6 +/- 5.4 vs
      28.1 +/- 2.4 years old). Some HCV isolates of subtype 2b from IDUs with acute
      hepatitis C were phylogenetically related to those from IDUs with chronic
      hepatitis C. By contrast, there was no phylogenetic segregation of HCV in IDUs
      with subtype 2a. HCV isolates from non-IDUs were genetically divergent from each
      other and those from IDUs, irrespective of the HCV subtype. CONCLUSION: Hepatitis
      C virus of the non-1b subtype, particularly subtype 2b, seemed to be transmitted
      between IDUs very recently in Yamaguchi prefecture, Japan.

PMID- 15482541
TI  - Images of interest. Gastrointestinal: ischemic enteritis and sickle cell disease.

PMID- 15482540
TI  - Factors contributing to ribavirin-induced anemia.
AB  - BACKGROUND AND AIM: Interferon and ribavirin combination therapy for chronic
      hepatitis C produces hemolytic anemia. This study was conducted to identify the
      factors contributing to ribavirin-induced anemia. METHODS: Eighty-eight patients
      with chronic hepatitis C who received interferon-alpha-2b at a dose of 6 MU
      administered intramuscularly for 24 weeks in combination with ribavirin
      administered orally at a dose of 600 mg or 800 mg participated in the study. A
      hemoglobin concentration of <10 g/dL was defined as ribavirin-induced anemia.
      RESULTS: Ribavirin-induced anemia occurred in 18 (20.5%) patients during
      treatment. A 2 g/dL decrease in hemoglobin concentrations in patients with anemia
      was observed at week 2 after the start of treatment. The hemoglobin concentration
      in patients with > or =2 g/dL decrease at week 2 was observed to be significantly
      lower even after week 2 than in patients with <2 g/dL decrease (P < 0.01). A
      significant relationship was observed between the rate of reduction of hemoglobin
      concentrations at week 2 and the severity of anemia (P < 0.01). Such factors as
      sex (female), age (> or =60 years old), and the ribavirin dose by body weight (12
      mg/kg or more) were significant by univariate analysis. CONCLUSIONS: Careful
      administration is necessary in patients > or =60 years old, in female patients,
      and in patients receiving a ribavirin dose of 12 mg/kg or more. Patients who
      experience a fall in hemoglobin concentrations of 2 g/dL or more at week 2 after
      the start of treatment should be monitored with particular care.

PMID- 15482542
TI  - Images of interest. Hepatobiliary and pancreatic: alveolar hydatid disease.

PMID- 15482543
TI  - Images of interest. Hepatobiliary and pancreatic: hepatic hydatid disease.

PMID- 15482544
TI  - Images of interest. Hepatobiliary and pancreatic: complications of hydatid
      disease.

PMID- 15482545
TI  - Polymorphism and addiction to alcohol.

PMID- 15482546
TI  - Autoimmune cholangitis in a patient with thymoma.
AB  - Autoimmune cholangitis is characterized biochemically by chronic cholestasis and
      histopathologically by chronic non-suppurative destructive cholangitis. It is
      associated with positive antinuclear antibody test and negative antimitochondrial
      antibody test results. Recently, we experienced a case of a 35-year-old woman
      with autoimmune cholangitis associated with thymoma who presented with pruritus,
      jaundice, chronic fatigue and anterior chest discomfort. Her laboratory
      examinations revealed marked increases in levels of serum alkaline phosphatase
      and gamma-glutamyl transpeptidase. In serological tests, antinuclear antibody was
      found, but antimitochondrial antibody was not. Liver biopsy findings were
      compatible with chronic non-suppurative destructive cholangitis. On computed
      tomography (CT) of the chest, a large anterior mediastinal mass was found. The
      mass was totally resected and the patient was treated with ursodeoxy cholic acid.
      Thereafter, her clinical symptoms improved and liver functions completely
      returned to the normal range. We describe here an uncommon association of
      autoimmune cholangitis with thymoma, which has not been reported previously in
      the English-written literature.

PMID- 15482547
TI  - Growth of hepatic angiomyolipoma indicating malignant potential.

PMID- 15482548
TI  - Remission of ulcerative colitis after anaphylaxis.

PMID- 15482549
TI  - Infliximab in the management of the extra-intestinal manifestations of Crohn's
      disease.

PMID- 15482550
TI  - Primary care experiences of medicare beneficiaries, 1998 to 2000.
AB  - OBJECTIVE: To examine changes in the quality of primary care experienced and
      reported by Medicare beneficiaries from 1998 to 2000. DESIGN: Longitudinal
      observational study. SETTING: Thirteen states with large, mature Medicare HMO
      markets. PARTICIPANTS: Probability sample of noninstitutionalized Medicare
      beneficiaries aged 65 and older enrolled in traditional Medicare (FFS) or a
      Medicare HMO. MEASUREMENTS AND MAIN RESULTS: We examined 2-year changes in 9
      measures derived from the Primary Care Assessment Survey (PCAS). The measures
      covered 2 broad areas of primary care performance: quality of physician-patient
      interactions (5 measures) and structural/organizational features of care (4
      measures). For each measure, we computed the change in each beneficiary's score
      (1998 vs 2000) and standardized effect sizes (ES). Results revealed significant
      declines in 3 measures of physician-patient interaction quality (communication,
      interpersonal treatment, and thoroughness of physical exams; P < or = .0001).
      Physicians' knowledge of patients increased significantly over the 2-year period
      (P < or = .001). Patient trust did not change (P = .10). With regard to
      structural/organizational features of care, there were significant declines in
      financial access (P < or = .001), visit-based continuity (P < .001), and
      integration of care (P < or = .05), while organizational access increased (P < or
      = .05). With the exception of financial access, observed changes did not differ
      by system (FFS, HMO). CONCLUSIONS: Over a 2-year period, the quality of seniors'
      interactions with their primary physicians declined significantly, as did other
      hallmarks of primary care such as continuity, integration of care, and financial
      access. This decline is in sharp contrast to the marked improvements in technical
      quality that have been measured over this period. In an era marked by substantial
      national investment in quality monitoring, measures of these elements of care are
      notably absent from the nation's portfolio of quality indicators.

PMID- 15482551
TI  - Changes in rates of beta-blocker use in community hospital patients with acute
      myocardial infarction.
AB  - OBJECTIVE: To examine changes in the rate of beta-blocker (BB) use at admission,
      in hospital, and at discharge between 1994 and 1995 (MICH I) and 1997 (MICH II)
      in patients with acute myocardial infarction (AMI). DESIGN: Comparison of two
      prospectively enrolled cohorts. SETTING: Five mid-Michigan community hospitals.
      PATIENTS: We studied 287 MICH I patients and 121 MICH II patients with AMI who
      had no contraindications to BB use from cohorts of consecutively admitted cases
      of AMI (814 in MICH I; 500 in MICH II). RESULTS: Prescription of BBs to ideal
      patients with AMI increased in patients with previous history of myocardial
      infarction on arrival at the hospital (12.5% vs 36.0%; P= .01), in hospital
      (47.0% vs 76%; P < .01), and at discharge (34.0% vs 61.9%; P < .01). Neither race
      nor gender was a predictor of BB use. Younger age predicted BB prescription at
      discharge (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.32 to 3.23).
      Later study cohort was the most important predictor of BB use in hospital (OR,
      3.4; 95% CI, 2.09 to 5.25). CONCLUSION: BB use improved dramatically over the
      study period, but additional work is needed to improve use of BB after discharge
      and among elderly patients with AMI.

PMID- 15482552
TI  - The medical care utilization and costs associated with migraine headache.
AB  - OBJECTIVE: To describe the medical care use and costs associated with migraine.
      DESIGN: Retrospective case-control design in which migraine case status was
      ascertained via validated telephone interview and linked with comprehensive
      claims data. Unadjusted and adjusted use and cost differences by migraine status
      were evaluated using exponential score tests and generalized estimating
      equations. SETTING AND PATIENTS: We interviewed 8,579 individuals to identify
      migraine cases (N = 1,265) and a random sample of nonmigraine controls (N =
      1,178) among eligible health plan enrollees aged 18 to 55. MEASURES: Survey
      responses were used to categorize individuals meeting the International Headache
      Society's diagnostic criteria for migraine with or without aura as migraine cases
      and to collect information on comorbid psychiatric symptoms. Claims data were
      used to compile annual medical and pharmaceutical use and costs, presence of
      migraine diagnosis, and other diagnosed comorbidities. RESULTS: Interview
      ascertained migraine cases used more outpatient visits (9.1 vs 6.8; P < .01),
      were more likely to be seen in the emergency department (20.7% vs 17.6%; P <
      .05), and were admitted to the hospital more (4.5% vs 2.8%; P < .05) compared to
      nonmigraine controls. Cases incurred significantly higher medical care costs
      ($2,761 vs $2,064; P < .01). Multivariable model results indicate that much of
      this increase in costs is due to the presence of major depressive symptoms as
      well as other diagnosed comorbidities that are more common among those with
      migraine. CONCLUSIONS: By combining validated telephone survey information to
      identify migraine cases and controls with comprehensive claims data, we found
      migraine cases incur higher medical care costs compared to controls. These
      increased costs are associated with the presence of psychiatric symptoms and
      other comorbidities.

PMID- 15482553
TI  - An evaluation of vignettes for predicting variation in the quality of preventive
      care.
AB  - OBJECTIVE: Clinical vignettes offer an inexpensive and convenient alternative to
      the benchmark method of chart audits for assessing quality of care. We examined
      whether vignettes accurately measure and predict variation in the quality of
      preventive care. DESIGN: We developed scoring criteria based on national
      guidelines for 11 prevention items, categorized as vaccine, vascular-related,
      cancer screening, and personal behaviors. Three measurement methods were used to
      ascertain the quality of care provided by clinicians seeing trained actors
      (standardized patients; SPs) presenting with common outpatient conditions: 1) the
      abstracted medical record from an SP visit; 2) SP reports of physician practice
      during those visits; and 3) physician responses to matching computerized case
      scenarios (clinical vignettes). SETTING: Three university-affiliated (including 2
      VA) and one community general internal medicine clinics. PATIENTS/PARTICIPANTS:
      Seventy-one randomly selected physicians from among eligible general internal
      medicine residents and attending physicians. MEASUREMENTS AND MAIN RESULTS:
      Physicians saw 480 SPs (120 at each site) and completed 480 vignettes. We
      calculated the proportion of prevention items for each visit reported or recorded
      by the 3 measurement methods. We developed a multiple regression model to
      determine whether site, training level, or clinical condition predicted
      prevention performance for each measurement method. We found that overall
      prevention scores ranged from 57% (SP) to 54% (vignettes) to 46% (chart
      abstraction). Vignettes matched or exceeded SP scores for 3 prevention categories
      (vaccine, vascular-related, and personal behavior). Prevention quality varied by
      site (from 40% to 67%) and was predicted similarly by vignettes and SPs.
      CONCLUSIONS: Vignettes can measure and predict prevention performance. Vignettes
      may be a less costly way to assess prevention performance that also controls for
      patient case-mix.

PMID- 15482554
TI  - Does patient-centered care improve provision of preventive services?
AB  - OBJECTIVES: While patient-centered care (PCC) is desirable for many reasons, its
      relationship to treatment outcomes is controversial. We evaluated the
      relationship between PCC and the provision of preventive services. METHODS: We
      obtained facility-level estimates of how well each VA hospital provided PCC from
      the 1999 ambulatory Veterans Satisfaction Survey. PCC delivery was measured by
      the average percentage of responses per facility indicating satisfactory
      performance from items in 8 PCC domains: access, incorporating patient
      preferences, patient education, emotional support, visit coordination, overall
      coordination of care, continuity, and courtesy. Additional predictors included
      patient population and facility characteristics. Our outcome was a previously
      validated hospital-level benchmarking score describing facility-level performance
      across 12 U.S. Preventive Services Task Force-recommended interventions, using
      the 1999 Veterans Health Survey. RESULTS: Facility-level delivery of preventive
      services ranged from an overall mean of 90% compliance for influenza vaccinations
      to 18% for screening for seat belt use. Mean overall PCC scores ranged from
      excellent (>90% for the continuity of care and courtesy of care PCC domains) to
      modest (<70% for patient education). Correlates of better preventive service
      delivery included how often patients were able to discuss their concerns with
      their provider, the percent of visits at which patients saw their usual provider,
      and the percent of patients receiving >90% of care from a VA hospital.
      CONCLUSION: Improved communication between patients and providers, and continuity
      of care are associated with increased provision of preventive services, while
      other aspects of PCC are not strongly related to delivery of preventive services.

PMID- 15482555
TI  - Development and validation of a functional morbidity index to predict mortality
      in community-dwelling elders.
AB  - OBJECTIVE: Functional measures have a great appeal for prognostic instruments
      because they are associated with mortality, they represent the end-impact of
      disease on the patient, and information about them can be obtained directly from
      the patient. However, there are no prognostic indices that have been developed
      for community-dwelling elders based primarily on functional measures. Our
      objective in this study was to develop and validate a prognostic index for 2-year
      mortality in community-dwelling elders, based on self-reported functional status,
      age, and gender. DESIGN: Population-based cohort study from 1993 to 1995.
      SETTING: Community-dwelling elders within the United States. PARTICIPANTS:
      Subjects, age > or =70 (N = 7,393), from the Asset and Health Dynamics Among the
      Oldest Old study. We developed the index in 4,516 participants (mean age 78, 84%
      white, 61% female), and validated it in 2,877 different participants (mean age
      78, 73% white, 61% female). MAIN OUTCOME MEASURES: Prediction of 2-year mortality
      using risk factors such as activities of daily living, instrumental activities of
      daily living, additional measures of physical function, age, and gender. RESULTS:
      Overall mortality was 10% in the development cohort and 12% in the validation
      cohort. In the development cohort, 6 independent predictors of mortality were
      identified and weighted, using logistic regression models, to create a point
      scale: male gender, 2 points; age (76 to 80, 1 point; >80, 2 points); dependence
      in bathing, 1 point; dependence in shopping, 2 points; difficulty walking several
      blocks, 2 points; and difficulty pulling or pushing heavy objects, 1 point. We
      calculated risk scores for each patient by adding the points of each independent
      risk factor present. In the development cohort, 2-year mortality was 3% in the
      lowest risk group (0 to 2 points), 11% in the middle risk group (3 to 6 points),
      and 34% in the highest risk group (>7 points). In the validation cohort, 2-year
      mortality was 5% in the lowest risk group, 12% in the middle risk group, and 36%
      in the highest risk group. The c-statistics for the point system were 0.76 and
      0.74 in the development and validation cohorts, respectively. CONCLUSIONS: This
      prognostic index, which relies solely on self-reported functional status, age,
      and gender, provides a simple and accurate method of stratifying community
      dwelling elders into groups at varying risk of mortality.

PMID- 15482556
TI  - Trends in the use of feeding tubes in North Carolina hospitals.
AB  - OBJECTIVE: National data describing the placement of feeding tubes demonstrated a
      rapid increase in use in the early and mid-1990s. In the past several years,
      substantial concerns have arisen regarding the appropriateness of the procedure
      in many chronically ill patients. The purpose of this study is to determine
      whether the use of feeding tubes has continued to increase through the 1990s
      despite these widely publicized concerns. DESIGN: Repeated measure cross
      sectional study of the North Carolina Discharge Database. SETTING: Analyses of
      all nonfederal hospital inpatient admissions in North Carolina. MEASUREMENTS AND
      MAIN RESULTS: We examined the absolute numbers and rates of feeding tube
      placements from 1989 to 2000. The rate of feeding tube placement increased from
      59/100,000 persons in 1989 to 94/100,000 persons in 2000, an overall 60% increase
      with slowing in the rate of increase in the late 1990s. However, when outpatient
      procedures were included, the increase in tube feeding continued throughout the
      11-year period of observation. The increase was due to an increase in utilization
      within all hospitals over the time period. Utilization did not differ between
      profit and not for profit hospitals. The relative growth rate of inpatient
      feeding tube placement did not differ by age group but the absolute increase was
      greatest in those age 75 years and over. CONCLUSIONS: Our study demonstrates that
      the use of feeding tubes has continued to increase through the 1990s. This
      increase occurred despite ongoing controversy in the medical literature about
      feeding tube placement in chronically ill patients.

PMID- 15482557
TI  - Validity of a self-reported history of a positive tuberculin skin test. A
      prospective study of drug users.
AB  - OBJECTIVE: To define the prevalence of and factors associated with having a
      negative purified protein derivative (PPD) among persons who self-report a prior
      positive PPD and to define the safety of repeat testing in such persons. DESIGN:
      Observational cohort study. SETTING: Methadone maintenance program with onsite
      primary care. PATIENTS/PARTICIPANTS: Current or former drug users enrolled in
      methadone maintenance treatment. INTERVENTIONS: Structured interview, tuberculin
      skin testing regardless of self-reported PPD status, and anergy testing.
      MEASUREMENTS AND MAIN RESULTS: Nearly one third (31%) of participants who self
      reported a prior positive PPD had a negative measured PPD, despite receipt of a
      "booster" PPD. A single participant (0.5%) blistered in response to the PPD
      without lasting ill effect. Participants with PPD results discordant from their
      history were more likely to be HIV-seropositive and nonreactive to the anergy
      panel. The discordance rate among HIV-infected participants was 43%, and was
      largely attributable to immune dysfunction. Among HIV-seronegative participants,
      the discordance rate was 27%. Recent crack-cocaine use was independently
      associated with discordance in the absence of HIV infection. CONCLUSIONS: We
      confirmed that planting a PPD in patients who self-report a positive PPD history
      confers minimal risk. Substantial rates of discordance exist between self
      reported history of a positive PPD and measured PPD status. Further research is
      needed to define the optimal management of PPD-negative patients who self-report
      a prior positive PPD and who have not received prior treatment for latent
      tuberculosis.

PMID- 15482558
TI  - Managing dyslipidemia in chronic kidney disease.
AB  - OBJECTIVE: Patients with chronic kidney disease (CKD) are at higher risk for
      cardiovascular disease (CVD) than patients in the general population. One
      potentially modifiable risk factor for CVD in patients with CKD is dyslipidemia.
      In the current manuscript we review observational and trial data assessing
      dyslipidemia and its treatment in this patient population. RESULTS: Observational
      studies have noted a "reverse epidemiology" in patients with CKD such that low
      total cholesterol levels are associated with a higher mortality rate. The complex
      lipid profile of patients with CKD also raises questions as to whether lipid
      lowering therapy will be beneficial in this patient population. Although there
      are only a few trials assessing the relationship between lipid-lowering therapy
      and CVD outcomes in CKD patients, many lipid-lowering medications are both safe
      and effective. In addition, there is suggestive evidence that statin therapy, in
      particular, also may reduce inflammation and slow the decline in glomerular
      filtration rate (GFR) in patients during the earlier stages of CKD. CONCLUSION:
      Because of the high rate of CVD in patients with CKD and the overall safety of
      most medical therapies for dyslipidemia in CKD, current guidelines from the
      National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommend
      aggressive therapy of dyslipidemia. These guidelines do, however, acknowledge the
      paucity of trial data in this patient population. There are 3 ongoing randomized
      controlled trials that are assessing the effect of statin therapy on CVD
      outcomes. These studies will hopefully provide definitive answers as to the
      appropriate treatment of dyslipidemia in CKD.

PMID- 15482559
TI  - When is medical treatment futile? A guide for students, residents, and
      physicians.
AB  - A difficult ethical conundrum in clinical medicine is determining when to
      withdraw or withhold treatments deemed medically futile. These decisions are
      particularly complex when physicians have less experience with these discussions,
      when families and providers disagree about benefits from treatment, and when
      cultural disparities are involved in misunderstandings. This paper elucidates the
      concept of "medical futility," demonstrates the application of futility to
      practical patient care decisions, and suggests means for physicians to negotiate
      transitions from aggressive treatment to comfort care with patients and their
      families. Ultimately, respect of persons and beneficent approaches can lead to
      ethically and morally viable solutions.

PMID- 15482560
TI  - Barriers to excellent end-of-life care for patients with dementia.
AB  - While great strides have been made recently in improving end-of-life care in the
      United States, people with dementia often die with inadequate pain control, with
      feeding tubes in place, and without the benefits of hospice care. In this paper,
      we discuss the most important and persistent challenges to providing excellent
      end-of-life care for patients with dementia, including dementia not being viewed
      as a terminal illness; the nature of the course and treatment decisions in
      advanced dementia; assessment and management of symptoms; the caregiver
      experience and bereavement; and health systems issues. We suggest approaches for
      overcoming these barriers in the domains of education, clinical practice, and
      public policy. As the population ages, general internists increasingly will be
      called upon to provide primary care for a growing number of patients dying with
      dementia. There are great opportunities to improve end-of-life care for this
      vulnerable and underserved population.

PMID- 15482561
TI  - Primary care experience.

PMID- 15482562
TI  - Death and primary care.

PMID- 15482563
TI  - Immunohistochemical expression of 14-3-3 sigma protein in various histological
      subtypes of uterine cervical cancers.
AB  - 14-3-3 sigma (sigma) has been a major G2/M checkpoint control gene and has
      demonstrated that its inactivation in various cancers occurs mostly by epigenetic
      hypermethylation, not by genetic change. In order to confirm 14-3-3sigma protein
      expression together with p16 and p53 in cervical cancers, immunohistochemistry
      was performed using various histological subtypes of cervical cancers and
      dysplasia. Strong and diffuse immunoreactivity for 14-3-3sigma was uniformly
      observed in all the cervical dysplasia (17/17) and squamous cell carcinomas
      (29/29) including human papillomavirus (HPV)-negative cases. Even in
      adenosquamous carcinomas and adenocarcinomas of the cervix, immunohistochemical
      expression of 14-3-3sigma was shown with relatively high frequency (13/15, 87%
      and 22/27, 81%). In the in situ hybridization study, mRNA of 14-3-3sigma was
      expressed in six of eight immunohistochemical-negative cases. Therefore, the
      undetectable expression of 14-3-3sigma protein in cervical cancers might, at
      least in part, be due to a proteolysis not epigenetic hypermethylation. It is of
      interest that cancers without 14-3-3sigma expression were predominantly those
      lacking HPV DNA, and that there were no cases with concomitant inactivation of 14
      3-3sigma and p16 in the present study. These observations are consistent with the
      hypothesis that inactivation of either 14-3-3sigma or p16 has an effect
      equivalent to the expression of E6 and E7 oncoproteins of HPV.

PMID- 15482564
TI  - Uterine lipoleiomyoma: a histopathological review of 17 cases.
AB  - Lipoleiomyoma is a rare uterine tumor. The exact frequency and proliferation
      activity are not yet known. This study aims to know the frequency and evaluate
      the relation with renal angiomyolipoma. Lipoleiomyoma cases were
      immunohistochemically stained by antibodies for Ki-67, melanoma specific antigen
      HMB45, S-100 protein, and alpha smooth muscle actin (alpha-SMA). Frequency of
      uterine lipoleiomyoma among uterine myomatous tumor was 17/4904 (0.35%) in the
      Department of Human Pathology, Field of Oncology, Kagoshima University Graduate
      School database (1983-2003). Patients ranged from 45 to 74 years of age, and 10
      cases were associated with leiomyoma. Six of 17 (35%) cases showed areas with
      renal angiomyolipoma-like vessels and atypical cellular features. Immunostaining
      was available in 12 cases. By Ki-67 labeling index, both muscle (average 1.38%)
      and fat (average 1.17%) portions of the tumor had greater proliferation than
      normal myometrium (average 0.76%), which suggests that fat portions of the tumor
      are proliferating adipose tissue rather than fatty degeneration of muscular
      counterpart. HMB45 antigen, which is positive in renal angiomyolipoma, was
      negative in three uterine cases having angiomyolipoma-like vessels (3/12).
      However, HMB45 antigen was positive in spindle-shaped tumor cells of three cases
      (3/12) which lacked angiomyolipoma-like vessels. Presence of angiomyolipoma-like
      blood vessels in these tumors is not an uncommon feature. However, the diagnosis
      of uterine angiomyolipoma should not be based on the result of HMB45 antigen
      immunoreactivity alone.

PMID- 15482565
TI  - Histopathological changes of cervical tissue in women with systemic sclerosis.
AB  - Systemic sclerosis is a connective tissue disease that can affect almost any
      organ of the body. The clinical aspects of systemic sclerosis on the reproductive
      system have been studied in large series, and an increased rate of cesarean
      section has been reported. For this reason, in the present study the
      histopathological features of cervical specimens of hysterectomyzed women with
      systemic sclerosis were evaluated. An increased frequency of vascular and stromal
      abnormalities in cervical specimens of women with systemic sclerosis were
      observed. Vascular medial hypertrophy, intimal thickening, and fibrosis were more
      often encountered in the cervical specimens of the patients with systemic
      sclerosis. Some of the histopathological features also showed correlation with
      the clinical profile of the disease. The patients with vascular medial
      hypertrophy in their cervical specimens were older, had a higher Rodnan score,
      and had longer duration of the disease. In contrast to vascular medial
      hypertrophy, periadventitial edema was found in the cervical specimens of the
      patients who were younger, had a lower Rodnan score, and had shorter duration of
      the disease. It was concluded that the problems that are seen in common obstetric
      and gynecological practices in patients with systemic sclerosis may be explained
      by these tissue abnormalities.

PMID- 15482567
TI  - Decreased expression of aquaporin-5 in bleomycin-induced lung fibrosis in the
      mouse.
AB  - The expression of aquaporin-5, the major water channel expressed in alveolar,
      tracheal, and upper bronchial epithelium, is significantly down-regulated during
      acute lung injury. In the present study, the expression of aquaporin-5 in two
      different mouse models of lung fibrosis was evaluated. Lung fibrosis was induced
      by intratracheal and by subcutaneous infusion of bleomycin. The expression of
      aquaporin-5 was investigated by immunohistochemical studies and by polymerase
      chain reaction. There were many cells with loss of aquaporin-5 immunoreactivity
      in type I alveolar epithelial cells in the mouse models of lung fibrosis.
      Immunohistochemistry of lung tissue in aquaporin-5 knockout mice revealed a
      fibrotic phenotype with increased deposition of extracellular collagen type I in
      thickened alveolar walls. Semiquantitative analysis of aquaporin-5 mRNA
      expression showed more abundant content of aquaporin-5 in the lung of the normal
      mouse compared to the mouse with lung fibrosis. The results of this study showed,
      for the first time, that chronic lung injury and lung fibrosis is associated with
      decreased protein and mRNA expression of aquaporin-5 in the lung.

PMID- 15482566
TI  - Differential analysis of two-dimension gel electrophoresis profiles from the
      normal-metaplasia-dysplasia-carcinoma tissue of human bronchial epithelium.
AB  - Processes involved in malignant transformation of the lung from preneoplasia are
      poorly understood. To better understand this process, two-dimensional
      polyacrylamide gel electrophoresis (2-D PAGE) profiles of proteins from the
      normal, metaplasia, dysplasia and carcinoma tissues of human bronchial epithelia
      were examined by differential proteomic analysis. The selected differential
      protein-spots were identified by peptide mass fingerprint based on matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry and
      database searching. The average spots for normal epithelium, metaplasia,
      dysplasia and invasive carcinoma were 1189.50 +/- 39.89, 1227.00 +/- 37.90,
      1273.00 +/- 43.31 and 1326.00 +/- 66.63, respectively. Well-resolved,
      reproducible 2-D PAGE patterns of the normal-metaplasia-dysplasia-carcinoma
      tissues of bronchial epithelia were obtained. After matching, the number of spots
      of differential proteins between normal tissue and metaplasia, metaplasia and
      dysplasia, and dysplasia and invasive cancer tissues were 31.50 +/- 7.67, 41.00
      +/- 9.07 and 56.00 +/- 8.96, respectively. In total, 35 differential proteins,
      expressed only at the later stage of a two-stage comparison, were identified,
      some of which are known to be involved in regulating the processes of
      proliferation, differentiation and signal transduction. Current data in this
      study, for the first time, provide the basis for identification of potential
      tumor markers of human lung squamous carcinoma and their involvement in the
      progression of malignant transformation of bronchial epithelium.

PMID- 15482568
TI  - Mucinous cystadenocarcinoma of the breast coexisting with infiltrating ductal
      carcinoma.
AB  - A recently described and rare variant of breast carcinoma, mucinous
      cystadenocarcinoma (MCA), is reported in a 65-year-old post-menopausal woman. She
      presented with a gradually enlarged breast tumor. A well-circumscribed tumor
      measuring about 3 cm in diameter was noted in the mammographic and
      ultrasonographic examinations. The mammographic and ultrasonographic findings
      were indistinguishable from more common mucinous carcinoma (colloid carcinoma) of
      the breast. The gross appearance of the tumor was well-defined and cystic,
      consisting of abundant transparent to bloody mucin, as well as whitish solid
      parts. Microscopically, the tumor was characterized by abundant extracellular and
      intracellular mucin. It looked like a mucinous cystic neoplasm of the ovary and
      pancreas. Particularly, few microscopic foci of ordinary intermediate-grade
      infiltrating ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) were
      observed around the main lesion in this case. A transition from ordinary DCIS to
      MCA in situ was found. It might indicate MCA derives from a metaplasia process of
      ordinary DCIS. MCA can be easily differentiated from mucinous carcinoma by quite
      different histologic and immunohistochemical findings. According to the
      previously reported and present cases, MCA of the breast more commonly affects
      elderly women and has a relatively favorable prognosis.

PMID- 15482569
TI  - Combined signet ring cell and glassy cell carcinoma of the uterine cervix arising
      in a young Japanese woman: a case report with immunohistochemical and
      histochemical analyses.
AB  - Signet ring cell carcinoma and glassy cell carcinoma are both rare histological
      subtypes of uterine cervical cancer. This report is of a case of uterine cervical
      carcinoma arising in a 29-year-old woman who had major components of signet ring
      cell carcinoma and glassy cell carcinoma within the same tumor. Histochemical and
      immunohistochemical analyses, including high and low molecular weight
      cytokeratins, p63 and MUC5AC, additionally demonstrated the squamous and
      adenocarcinomatous differentiation in the neoplastic cells, which showed
      otherwise unclassifiable morphology on the haematoxylin-eosin sections. A wide
      range of differentiation described above supports the speculation that glassy
      cell carcinoma may arise from the multipotential immature cells that can
      differentiate into both squamous and glandular cells. It would be precise to
      classify this tumor as adenosquamous carcinoma. Although adenosquamous carcinoma
      is not a rare histological subtype in the uterine cervix, it should be necessary
      to report the presence of glassy cells and signet ring cells when present because
      the presence of both components is associated with an unfavorable clinical
      behavior.

PMID- 15482570
TI  - Coexisting Brenner tumor and struma ovarii in the right ovary: case report and
      review of the literature.
AB  - A bilateral ovarian tumor composed of mixed Brenner tumor and struma ovarii in
      the right ovary and mature cystic teratoma in the left ovary, is described. Mixed
      Brenner tumor and struma ovarii is rare; eight cases are reviewed. In this case,
      in addition to the typical Brenner tumor and struma ovarii, some nests composed
      of both Brenner tumor and struma ovarii in one nest were found in the right
      ovarian tumor. Immunohistochemically, the struma ovarii is stained for
      thyroglobulin, and Brenner nests showed various degrees of positive stain for
      thyroglobulin, which is a specific finding. Brenner tumor, in this case, may
      produce thyroglobulin or have a receptor to thyroglobulin or analog of
      thyroglobulin. The origin of mixed Brenner tumor and struma ovarii may be germ
      cell, as described in some literature, or the Brenner tumor may be of a
      metaplastic nature, although the Brenner tumor is fourfold the size of struma
      ovarii in the case presented.

PMID- 15482571
TI  - Rheumatoid arthritis with diffuse pulmonary rheumatoid nodules.
AB  - Rheumatoid nodules in dermal or subcutaneous tissues, while indicative of
      rheumatoid arthritis, are very rare. It is even less common to identify these
      rheumatoid nodules by biopsy as well as in autopsy materials from lung tissue.
      These nodules may be single or multiple, which seldom cause respiratory symptoms.
      Here, a patient with diffuse pulmonary rheumatoid nodules and interstitial
      fibrosis throughout both lungs, is described. The patient, with articular
      symptoms and seropositivity, exhibited a rapid clinical course and died of
      respiratory failure 3 months after the appearance of dyspnea. Chest radiography
      indicated interstitial pneumonitis with bilateral diffuse peripheral shadows. At
      autopsy, numerous rheumatoid nodules and interstitial fibrosis had destroyed both
      lungs, such that no residual normal pulmonary tissue remained. It is believed
      that this was an extremely rare case exhibiting large numbers of rheumatoid
      nodules throughout the lungs. Findings with this patient indicate that, in
      patients with rheumatoid arthritis, clinical interstitial pneumonitis confirmed
      radiologically does not exclude the existence of rheumatoid lung nodules.

PMID- 15482572
TI  - Esophageal carcinosarcoma with basaloid squamous carcinoma and rhabdomyosarcoma
      components with TP53 mutation.
AB  - Carcinosarcoma of the esophagus is a rare tumor with a distinct pathological
      entity having squamous cell carcinoma as the most described carcinomatous
      component. This paper reports the first case of carcinosarcoma of the esophagus
      that showed predominant basaloid squamous carcinoma component in addition to
      squamous cell carcinoma and poorly differentiated carcinoma and sarcoma
      component. A 64-year-old male patient consulted for dysphasia and chest pain was
      examined and found to have gastrointestinal fiber-endoscope and a polypoid growth
      in the lower third of the esophagus. Partial esophagectomy was performed and the
      excised tumor showed histological features of carcinosarcoma with heterogeneous
      carcinomatous components with dominance of basaloid squamous carcinoma and
      minority of squamous cell carcinoma, poorly differentiated carcinoma, and
      sarcomatous component, immunohistochemically proven to be rhabdomyosarcoma.
      Immunohistochemical study and TP53 mutation analysis was carried out to explain
      the histogenesis of this rare tumor. The distinct immunohistochemical profiles of
      the carcinomatous and sarcomatous components suggested the possibility of
      transition from a carcinomatous to a sarcomatous component. The similar TP53
      mutation in the carcinomatous and sarcomatous component suggested each of these
      components had the same origin, that is, the tumor was monoclonal in origin.

PMID- 15482574
TI  - Exploring the effects of psychosocial and acculturation factors on drinking
      behavior among aboriginal adolescents in Taiwan.
AB  - The purpose of this study was to examine the effects of psychosocial and
      acculturation factors on drinking behavior among Taiwanese aboriginal teenagers.
      Stratified random sampling was used to select six of the 19 aboriginal schools in
      Taipei, Pingtung, Hualien, and Taitung counties. A total of 495 student subjects
      were enrolled in the study, including 290 boys and 205 girls, with classification
      by tribe of 206 Amis, 97 Atayal, 94 Paiwan, 47 Bunun, 19 Rukai, 15 Yami, 10
      Puyuma, two Saisiyat, one Tsou, and four unknown. The analysis indicated that the
      psychosocial and acculturation factors that directly influenced drinking
      behaviors of aboriginal teenagers were: self-efficacy, drinking behaviors of
      parents, peer alcohol use, social assimilation, social attitude, and territorial
      attitude. In this model, peer alcohol use had the most prominent impact on
      drinking behavior among aboriginal teenagers. The findings suggest that parents'
      behaviors play a significant role in the development of problematic drinking
      behavior in the aboriginal teenager through observation and imitation, and also
      that self-efficacy and the level of acculturation influences drinking behavior in
      aboriginal teenagers.

PMID- 15482575
TI  - The possible factors affecting suicide attempts in the different phases of the
      menstrual cycle.
AB  - This study was designed to investigate whether there is a relationship between
      the menstrual cycle and suicide attempts, and to determine the factors affecting
      suicide attempts in different phases of the menstrual cycle. The study sample
      included 52 women who were admitted to the emergency room because of a suicide
      attempt. The incidence of suicide attempts in menstrual follicular phase (MFP)
      was significantly higher than in other phases. No significant difference of socio
      demographic and clinical characteristics was observed between MFP and the other
      phases. Also, hormone levels of patients who attempted suicide were not different
      from those of healthy control subjects. In spite of the fact that suicide
      attempts were often made in MFP, there was substantial difficulty in explaining
      why this frequency was different than other phases. Furthermore, the event may be
      linked to low estrogen and progesterone levels in this phase. It has, however,
      been thought that hormonal effects cannot be responsible alone for suicide
      attempts.

PMID- 15482576
TI  - Impairment of recognition memory in schizophrenia: event-related potential study
      using a continuous recognition task.
AB  - Recognition memory and the dissociation of immediate and delayed repetition in
      schizophrenic patients were investigated using event-related potential (ERP) and
      a continuous word recognition task. In total, 14 schizophrenic patients and 14
      age and gender-matched control subjects, were recruited. Among 240 stimulus words
      used, 40 words were not repeated, 100 were repeated immediately, and 100 were
      repeated after five intervening words. Both schizophrenic and control groups
      responded faster to words repeated immediately than to words repeated after a
      delay and to new words. However, schizophrenic patients responded less accurately
      to words repeated immediately and to words repeated after a delay than the
      controls. In terms of ERP, schizophrenic patients showed significantly reduced
      N200, late positive component (LPC), and N400 amplitudes, and a more frontally
      distributed N200 topography than the controls. For controls, immediate repetition
      was associated with a large LPC amplitude and the absence of N400, while delayed
      repetition was associated with a small LPC amplitude and the presence of N400.
      However, this dissociation between immediate and delayed repetition was not
      observed in schizophrenic patients. All of these results suggest that
      schizophrenic patients have recognition memory impairment, the cause of which may
      range from early encoding, and memory search to late retrieval.

PMID- 15482577
TI  - Autochthonous experience, heightened awareness, and perception distortion in
      patients with schizophrenia: a symptomatological study.
AB  - Early symptoms of schizophrenia' (ESS) proposed by Nakayasu, are present during
      schizophrenic prodromal periods. Some of these symptoms can continue after the
      florid manifestation of the disease and the patients often experience them with
      ego-alien feelings. Autochthonous experience, heightened awareness, and
      perception distortion (AHP) were selected from the list of ESS. The aim of this
      study was to confirm both prevalence and specificity of AHP in patients with
      schizophrenia as well as the relevance of the presence of AHP to symptomatology
      of schizophrenia. A structured interview was conducted to identify the presence
      of AHP in three groups of subjects; a schizophrenia group (Sc) with 37 patients,
      an affective disorder group (AD) with 27 patients, and a control group (NC) with
      39 people. The prevalence of AHP was compared among the groups. Within the Sc,
      the relevance of AHP to Brief Psychiatric Rating Scale (BPRS) was assessed. AHP
      were present significantly more frequently in the Sc. The total scores for BPRS
      in the schizophrenic patients with AHP were significantly higher than in the
      patients without AHP. There was close correlation between AHP and BPRS items,
      with the degree of relevance depending on the form or perceptual domain. In
      conclusion, AHP were characteristic of patients with frank schizophrenia. To
      judge whether AHP were adequately specific to frank schizophrenia, further
      research of larger subjects is needed. Understanding the characteristics of AHP
      in patients with frank schizophrenia is important in the symptomatological
      evaluation of schizophrenia.

PMID- 15482578
TI  - Inter-episode mood lability in mood disorders: residual symptom or natural course
      of illness?
AB  - Residual depressive symptoms are common in mood disorders. Inter-episode mood
      lability (IML; i.e. frequent ups and downs of mood) is understudied as a possible
      residual symptom. The study aim was to find the frequency of IML, and to find if
      it was more likely to be a residual symptom or if it was instead part of the
      natural course of mood disorders. Consecutive 89 bipolar-II (BP-II) and 89 major
      depressive disorder (MDD) outpatients who were not on psychoactive drugs, were
      interviewed by the Structured Clinical Interview for the 4th edition of the
      Diagnostic and Statistical Manual of Mental Disorders as modified by Benazzi and
      Akiskal. Kraepelin's basic definition of IML (i.e. frequent up and down
      fluctuations of mood between episodes) was followed. IML was present in 48.3% of
      the patients, significantly more common in BP-II than in MDD (62.9% vs. 33.7%, P=
      0.000). The sample of BP-II and MDD plus IML, versus the sample BP-II and MDD
      without IML, had significantly more BP-II, lower age at onset, longer illness
      duration, more depressive recurrences, more depressions with atypical features,
      more depressive mixed states, and more family history of mood disorders. Logistic
      regression of IML versus recurrences, controlled for duration of illness, found
      odds ratio = 1.8, z= 1.6, P= 0.103. Forward stepwise multiple logistic regression
      of IML versus the variables found significant in the univariate analysis, showed
      that only BP-II (P = 0.002) and duration of illness (P = 0.015) were significant
      predictors of IML. IML was common in mood disorder outpatients. Its association
      with BP-II (an unstable disorder by definition) and duration of illness (but not
      with recurrences when controlled for illness duration), suggest that IML may be
      more likely to be part of the natural course of illness than the result of
      kindling induced by recurrences. Its association with depressive mixed state (a
      depression reported to be more difficult to treat) and the possibility that it
      may induce/facilitate recurrences (to be shown by prospective studies), support
      the need to better study IML for its possible important impact on treatment.

PMID- 15482579
TI  - Attention deficit hyperactivity symptoms and internet addiction.
AB  - The objective of this study was to evaluate the relationship between attention
      deficit-hyperactivity/impulsivity symptoms and Internet addiction. In total, 535
      elementary school students (264 boys, 271 girls; mean age, 11.0 +/- 1.0 years)
      were recruited. The presence or severity of Internet addiction was assessed by
      the Young's Internet Addiction test. Parents and teachers of the children
      completed the DuPaul's attention deficit hyperactivity disorder (ADHD) rating
      scale (ARS; Korean version, K-ARS) and Child Behavior Checklists. Children with
      the highest and lowest quartiles in K-ARS scores were defined to be in ADHD and
      non-ADHD groups, respectively. Five children (0.9%) met criteria for a definite
      Internet addiction and 75 children (14.0%) met criteria for a probable Internet
      addiction. K-ARS scores had significant positive correlations with Young's
      Internet Addiction test scores. The Internet addiction group had higher total
      scores of K-ARS and ADHD-related subcategories in the Child Behavior Checklists
      than the non-addiction group. The ADHD group had higher Internet addiction scores
      compared with the non-ADHD group. Therefore, significant associations have been
      found between the level of ADHD symptoms and the severity of Internet addiction
      in children. In addition, current findings suggest that the presence of ADHD
      symptoms, both in inattention and hyperactivity-impulsivity domains, may be one
      of the important risk factors for Internet addiction.

PMID- 15482580
TI  - Family functioning perceived by patients and their family members in three
      Diagnostic and Statistical Manual-IV diagnostic groups.
AB  - The aim of this study was to clarify the difference in the perception of family
      functioning measured on the Family Assessment Device (FAD) by Diagnostic and
      Statistical Manual-IV diagnoses (i.e. schizophrenia, major depressive disorder
      and bipolar disorder) and by raters (patients and family members). The subjects
      were 70 psychiatric outpatients paired with their family members (i.e. principal
      caretaker), divided into three groups based on the patient's diagnosis of
      schizophrenia (24 pairs), major depressive disorder (28 pairs) or bipolar
      disorder (18 pairs). They rated their perceived family functioning on the FAD.
      There was no significant difference in perceptions of family functioning between
      the three groups of family members, while there were differences between the
      patient groups in some FAD dimensions. Perceptions of family functioning were not
      significantly correlated between the schizophrenic patients and their family
      members. The perceptions of family functioning were correlated more strongly
      between patients and their family members in the bipolar group than between
      patients and family members in the other two diagnostic groups. As for the FAD
      Problem Solving dimension, the schizophrenia patients saw it more negatively than
      did their family members, whereas the depressive patients saw it more positively
      than did their family members. These results might reflect psychopathological
      characteristics of each disorder. When clinicians evaluate the family functioning
      of psychiatric patients, it is important to consider the diagnoses of patients as
      well as who assesses it.

PMID- 15482581
TI  - Quality of life and its correlates in HIV/AIDS male outpatients receiving highly
      active antiretroviral therapy in Taiwan.
AB  - Long-term care of human HIV and AIDS cases has raised quality of life (QoL)
      issues. The aim of this study was to identify QoL in HIV/AIDS male outpatients
      receiving highly active antiretroviral therapy (HAART) and its correlates in
      Taiwan. In total, 41 HIV/AIDS male outpatients receiving HAART yet presenting few
      symptoms of infection, were recruited for the study. Their QoL levels were
      measured with the Taiwan version of the Short Form of the World Health
      Organization Quality of Life questionnaire (WHOQOL-BREF). The relationships
      between QoL and demographic characteristics, social support, negative stressors,
      depression, characteristics of HIV infection, attitude toward HIV infection, and
      adverse effects of HAART, were examined. The results of the analysis reveal that
      multiple factors affect QoL for HIV/AIDS male outpatients receiving HAART,
      including severity of depression, deterioration of work function, inconvenience
      resulting from medication schedules and medical appointments, lack of social
      support, negative stressors, and adverse effects of HAART. The results provide
      screening factors so that clinicians can intervene to improve the QoL for their
      HIV patients.

PMID- 15482582
TI  - Can a less pejorative Chinese translation for schizophrenia reduce stigma? A
      study of adolescents' attitudes toward people with schizophrenia.
AB  - The term jing-shen-fen-lie-zheng (mind-split-disease) has been used to denote
      schizophrenia in Chinese societies. Many Asian countries, where the Chinese
      writing system is used, adopt a similar translation. This study examined whether
      a less pejorative name si-jue-shi-diao (dys-regulation of thought and perception)
      as a diagnostic label for symptoms of schizophrenia could reduce stigma.
      Secondary school students (n = 313) were randomly assigned to read a vignette
      with one of four labels: si-jue-shi-diao, jing-shen-fen-lie-zheng, jing-shen-bin
      (mental illness), and no label. Students expressed their social distance,
      stereotypes held, and attributions toward a young adult who met the Diagnostic
      and Statistical Manual-IV of Mental Health Disorders criteria for schizophrenia.
      It was found that psychiatric labeling did not have a statistically significant
      main effect on attitude measures. However, students with religious beliefs were
      more accepting toward the target individual associated with diagnostic label than
      one with no labeling. The results cast doubts that less pejorative labels can
      reduce the social stigma of schizophrenia. Some potential drawbacks in using
      politically correct terms to describe schizophrenia are highlighted.

PMID- 15482583
TI  - White matter hyperintensities in subjects with bipolar disorder.
AB  - There have been divergent reports on the prevalence and severity of white matter
      hyperintensities (WMH) on brain magnetic resonance (MR) images in subjects with
      bipolar disorder. In the present study, evaluations were made on the prevalence
      and severity of WMH in subjects with bipolar disorder using contiguous 3-mm thick
      MR slices as well as fluid attenuated inversion recovery (FLAIR) images. A
      detailed WMH rating system was employed to assess these WMH. A total of 43
      bipolar patients, as diagnosed by the Structured Clinical Interview from the
      Diagnostic and Statistical Manual-IV (SCID-IV), and 39 healthy comparison
      subjects were scanned using a 1.5-T whole body GE magnetic resonance scanner. WMH
      were assessed with a modified composite version of the Fazekas' and Coffey's
      rating scales to detect less severe WMH. Periventricular and subcortical WMH were
      coded separately. Subjects with bipolar disorder had greater prevalence of WMH
      abnormalities than comparison subjects (Bipolar, grade 1 = 11.6%, grade 2 = 9.3%,
      grade 3 = 7.0%; Comparison, grade 1 = 5.1%, grade 2 = 2.6%, grade 3 = 0%). This
      difference is mainly due to the differences in deep WMH (Bipolar, grade 1 =
      14.0%, grade 2 = 14.0%; Comparison, grade 1 = 7.7%, grade 2 = 0%). The current
      study confirms the higher prevalence of WMH in subjects with bipolar disorder.
      Differences of small-sized WMH abnormalities between groups were successfully
      detected using a large number of bipolar subjects and thinner sliced MR images
      with FLAIR.

PMID- 15482584
TI  - Where is help sought for depression or suicidal ideation in an elderly population
      living in a rural area of Japan?
AB  - Although suicide is increasingly becoming a social problem in Japan, especially
      among the elderly, little early intervention or suicide prevention is done. A
      project was begun which, since 1999, has aimed to detect depression at an early
      stage as a suicide prevention measure in a model area of Town A, which had a high
      suicide rate. In order to promote early intervention and prevention in a
      community, it is important to know where residents seek help if they become
      depressed or have suicidal ideation. Therefore, in the present study, help
      seeking behavior using case vignettes was investigated. Data from 230 residents
      (82 men, 148 women) in the model area of Town A, aged 65 or over, were analyzed
      in the present study. If participants were unable to answer by themselves due to
      physical condition, public health nurses read out each item and wrote in their
      answers. The relationship between help-seeking behavior and demographic
      variables, psychosocial variables, depressive symptoms and so forth, were
      examined. The results show that participation in mental health workshops
      facilitated consultation with specialists (e.g. primary care doctors and nurses).
      The expected effects of psychoeducation on the general public and specialists
      were considered.

PMID- 15482585
TI  - Long-term suppression of methamphetamine-induced c-Fos expression in rat striatum
      by the injection of c-fos antisense oligodeoxynucleotides absorbed in water
      absorbent polymer.
AB  - The use of water-absorbent polymer (WAP) as a hydrogel carrier for the slow
      delivery of antisense oligodeoxynucleotides (ODN) in the brain, was recently
      developed. In this experiment, 15-mer phosphorothioate ODN, complementary to c
      fos gene absorbed in WAP, was injected in the rat striatum. The expression of c
      Fos-immunoreactivity induced by methamphetamine (6 mg/kg, intraperitoneally)
      around the injection site was suppressed until 5 days after injection. Using this
      method, it was observed that unilateral injection with c-fos antisense ODN into
      the rat striatum caused robust ipsilateral rotations after methamphetamine
      challenge 4 days post injection. This method is simple, and the biological and
      behavioral effects of antisense ODN in WAP can be maintained for several days
      even after a single injection into the brain.

PMID- 15482586
TI  - Temperament and character profiles of patients with tension-type headache and
      migraine.
AB  - The aim of this present study was to evaluate the temperament and character
      profiles of persons with tension-type headache (TTH) and migraine, and to compare
      the results with those of healthy controls. The study population consisted of 81
      patients with TTH (60 female, 21 male) and 56 patients with migraine (34 female,
      17 male) aged 18-50 years, according to the criteria of the International
      Headache Society with age and gender - matched healthy control subjects (54
      female, 28 male). All participants were instructed to complete a self
      administered 240-item temperament and character inventory (TCI) questionnaire and
      Beck Depression Inventory (BDI). The TCI assesses four dimensions of temperament,
      namely, novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and
      persistence (P), and three dimensions of character, being self-directedness (SD),
      cooperativeness (C) and self-transcendence (ST). According to the TCI biosocial
      model, the temperament dimension HA is suggested to indicate central serotonergic
      turnover, which is further correlated with depressive state. It was found that
      mean BDI scores were significantly higher in patients with TTH and migraine than
      in those of the controls. The BDI scores were positively correlated with HA
      scores (r = 0.295, P < 0.001) and negatively correlated with SD (r = -0.386, P <
      0.001) and C scores (r = -0.164, P= 0.016). Multivariate analysis showed that BDI
      scores had significant covariation for HA, SD and C. Despite using the BDI score
      as a covariate, TTH patients had higher HA scores (P = 0.01) than did the control
      subjects. No significant differences were found between the groups regarding main
      NS, RD, P, SD, C and ST scores. Based on the main results of this study, it is
      suggested that higher serotonergic activity related to HA scores in TTH patients
      and their relationship with depressive symptomatology supports the role of
      central serotonergic involvement in TTH.

PMID- 15482587
TI  - Mental illness in a general hospital's family medicine clinic in Taiwan.
AB  - There has been a paucity of evidence-based information regarding mental illness
      in general medical settings among the Chinese population. Aims of the present
      study are to investigate the patterns and distribution of mental disorders among
      family medicine clinic attenders, illness behavior of attenders with such
      disorders, and the recognition and management given by family physicians for
      them. A random sample (n = 200) of patients attending a family medicine clinic in
      a medical center in Taiwan, received a standardized psychiatric assessment using
      the semistructured Clinical Interview Schedule (CIS) after they had seen the
      family physician. A total of 12 family physicians, who were blind to the
      psychiatric status of their patients, were then asked to assess the physical and
      psychological condition of the subjects. Of all study subjects, 51% had at least
      one psychiatric diagnosis based on the CIS assessment, and the corresponding
      figure was 21.5% from family physicians. While the specificity of psychiatric
      case identification among family physician was high (91%), the sensitivity was
      very low (30%), especially for depressive disorders and alcohol-related
      disorders. Because the same magnitude of psychiatric morbidity and similarly low
      detection rates by general medical physicians were found in other developing
      countries, the improvement in psychiatric education for medical students and
      family physicians is highly implicated there.

PMID- 15482588
TI  - Self-help groups reduce mortality risk: a 5-year follow-up study of alcoholics in
      the Tokyo metropolitan area.
AB  - The present study aimed to determine whether alcoholics who attend self-help
      groups experience fewer deaths than those who do not. Subjects were patients from
      the Alcoholism Treatment Program (ATP) of Matsuzawa hospital. A cohort of
      alcoholic patients recruited into a prospective study was followed from April
      1994 to March 1999. A total of 469 alcoholic patients met the International
      Classification of Diseases (10th edition) criteria for alcohol dependency. Of
      these, 94 patients refused to participate in the study, leaving a total of 375
      participants. After discharge from the ATP and a complete explanation of the
      present study, subjects decided whether to attend a self-help group (SHG) or not.
      The SHG comprised 208 subjects, and the non-self-help group (NSHG) comprised 167
      subjects. Outcomes were evaluated with regard to death during follow-up for a
      mean of 2.4 years. Death was ascertained through the records of the Setagaya
      Department of Health and Welfare center, Matsuzawa hospital and other hospitals,
      and through personal contact with informants, relatives, and significant others
      of subjects. Deaths were confirmed for 47 NSHG subjects and only five SHG
      subjects. NSHG displayed a significantly decreased cumulative survival compared
      with SHG (P < 0.0001). Cox proportion hazard analysis was used to examine
      variables that may help to predict mortality among alcoholics. Alcoholics who
      attended self-help groups differed from those who did not, with regard to
      mortality experience. Attending a self-help group represented the most important
      predictor of prognosis for alcoholics.

PMID- 15482589
TI  - Evaluating stigma against mental disorder and related factors.
AB  - This study attempted to identify forms of stigma against individuals with mental
      disorders and related factors. The subjects comprised 2632 people living in the
      area covered by the K health center in N prefecture. Factor analysis of the
      Mental Disorder Prejudice Scale (1211 valid responses) identified three factors:
      'rejection', 'peculiarity' and 'human rights alienation'. Regression analysis
      revealed that age, welfare activities, an active problem-solving attitude,
      lecture attendance, and previous contact, exerted independent effects with
      respect to 'rejection'. These results suggest the importance of disseminating
      accurate information and creating more opportunities for people to have
      meaningful interactions with people with mental disorders in order to dispell the
      stigma.

PMID- 15482590
TI  - Psychopathology and outcome of first-admission schizophrenic patients:
      hypochondriac-cenestopathic symptoms as predictors of an unfavorable outcome.
AB  - The outcome of first-admission schizophrenic patients at Jichi Medical School
      Hospital was investigated to identify outcome predictors of schizophrenia among
      the symptoms at the time of the first hospitalization. The subjects were 62
      schizophrenic patients, 29 females and 33 males, consecutively discharged from
      the Department of Psychiatry, Jichi Medical School Hospital, between June 1983
      and May 1988. The mean interval between first admission and follow-up was 13
      years. Eguma's Social Adjustment Scale was used to measure social outcome. The
      subjects were divided into two groups according to their rating on Eguma's Scale;
      a favorable outcome group and an unfavorable outcome group. Information on
      premorbid status and psychopathology at the time of the first hospitalization was
      obtained from clinical records and analyzed by comparing them between the two
      groups. Of the 62 patients, 56 were followed-up. Nine of the 56 patients followed
      up had died. While 47 patients were alive; 39 were receiving psychiatric
      treatment and eight were not. The 47 patients who were still living were divided
      into two groups; a favorable outcome group (n = 22), and an unfavorable outcome
      group (n = 25). No significant differences in premorbid status were found.
      Comparison of psychopathology at the time of the first hospitalization between
      the outcome groups revealed significant differences in lack of spontaneity and
      hypochondriac-cenestopathic symptoms. Lack of spontaneity may reflect negative
      symptomatology, while hypochondriac-cenestopathic symptoms may reflect a serious
      disturbance of ego function. There is a strong possibility that evaluation of
      body-related symptoms in schizophrenia will be helpful in predicting outcome.

PMID- 15482591
TI  - Forecasting the number of inpatients with schizophrenia.
AB  - There has been much discussion in Japan regarding the reduction of psychiatric
      beds. For effective healthcare planning, reliable forecasting is important. The
      purpose of this study was to predict the number of future schizophrenic
      inpatients using quantitative methodology. Data was obtained from a survey of
      schizophrenic inpatients conducted annually at the end of March by the Niigata
      Prefecture from 1974 to 2003. The numbers of schizophrenic inpatients in
      different age groups over a long period of time were used in a precise time
      series analysis to establish trends. Then these past trends were used to forecast
      inpatient numbers for future years. The pattern of ascents and declines of each
      inpatient group stratified by age appeared to be duplicated by the next older age
      group 10 years later. The numbers of inpatients with schizophrenia in 2013 and
      2023 are projected to be 78.5% and 56.7% of the number of patients in 2003,
      respectively. By 2033, the number is forecast to decline to 41.0% of the number
      in 2003. This study forecasts that inpatients with schizophrenia will decrease
      substantially over the next several decades. Policy should be designed to reflect
      this trend.

PMID- 15482592
TI  - Novel missense polymorphism in the regulator of G-protein signaling 10 gene:
      analysis of association with schizophrenia.
AB  - Dysfunction of neuronal signal transduction via G-protein has previously been
      speculated to be involved in the pathophysiology of schizophrenia. Regulator of G
      protein signaling (RGS) is a protein that acts as a GTPase-activator for Galpha
      protein. A total of 33 Japanese patients with schizophrenia were screened for
      mutations in the coding region of the RGS10 gene, and a novel missense
      polymorphism (Val38Met) in the RGS domain was detected. A case-control study did
      not reveal a significant association between this polymorphism and schizophrenia.
      The results do not provide evidence that the RGS10 gene is involved in biological
      vulnerability to schizophrenia.

PMID- 15482593
TI  - Primary alveolar hypoventilation syndrome combined with severe obstructive sleep
      apnea hypopnea syndrome in a post-middle-aged patient.

PMID- 15482594
TI  - Is cumulative frequency of mitochondrial DNA variants a biomarker for colorectal
      tumor progression?
AB  - To examine the relationship between mitochondrial DNA (mtDNA) alterations and
      colorectal tumorigenesis, we used high-resolution restriction endonucleases and
      sequencing to assess the mitochondrial genome from three histologic subtypes of
      colorectal adenomas (tubular = 8; tubulovillous = 9; and villous = 8), colorectal
      cancer (CRC) tissues = 27, and their matched surrounding normal tissue (MSNT) =
      52. The mitochondrial genomes were amplified using 9 pairs of overlapping primers
      and systematically analyzed by means of high-resolution analysis. DNA fragments
      showing a shift in banding patterns between the three adenomas, CRC, in
      comparison to the MSNT were sequenced to identify the mtDNA alterations. A total
      of thirty-eight germ-line mtDNA variants were observed in this study. Twenty-two
      of the thirty-eight were identified as mutations and 59% (13 of 22) were silent
      mutations and one was a 1-bp insertion. Sixteen of thirty-eight were distinct
      SNPs in flanking regions of the restriction sites and, 6 of the 16 (37%) SNPs
      were not previously reported. Most of these mutations/SNPs were homoplasmic and
      distributed in various regions of mitochondrial genes including the 16S and 12S
      rRNA. Based on our results, mtDNA germline variants increased in prevalence with
      adenoma CRC progression. To the best of our knowledge, this is the first report
      to show an increased prevalence of mitochondrial gene variants in CRC
      tumorigenesis.

PMID- 15482595
TI  - Reduction of arsenic content in a complex galena concentrate by Acidithiobacillus
      ferrooxidans.
AB  - BACKGROUND: Bioleaching is a process that has been used in the past in mineral
      pretreatment of refractory sulfides, mainly in the gold, copper and uranium
      benefit. This technology has been proved to be cheaper, more efficient and
      environmentally friendly than roasting and high pressure moisture heating
      processes. So far the most studied microorganism in bioleaching is
      Acidithiobacillus ferrooxidans. There are a few studies about the benefit of
      metals of low value through bioleaching. From all of these, there are almost no
      studies dealing with complex minerals containing arsenopyrite (FeAsS). Reduction
      and/or elimination of arsenic in these ores increase their value and allows the
      exploitation of a vast variety of minerals that today are being underexploited.
      RESULTS: Arsenopyrite was totally oxidized. The sum of arsenic remaining in
      solution and removed by sampling represents from 22 to 33% in weight (yield) of
      the original content in the mineral. The rest of the biooxidized arsenic form
      amorphous compounds that precipitate. Galena (PbS) was totally oxidized too,
      anglesite (PbSO4) formed is virtually insoluble and remains in the solids. The
      influence of seven factors in a batch process was studied. The maximum rate of
      arsenic dissolution in the concentrate was found using the following levels of
      factors: small surface area of particle exposure, low pulp density, injecting air
      and adding 9 K medium to the system. It was also found that ferric chloride and
      carbon dioxide decreased the arsenic dissolution rate. Bioleaching kinetic data
      of arsenic solubilization were used to estimate the dilution rate for a
      continuous culture. Calculated dilution rates were relatively small (0.088-0.103
      day(-1)). CONCLUSION: Proper conditions of solubilization of arsenic during
      bioleaching are key features to improve the percentage (22 to 33% in weight) of
      arsenic removal. Further studies are needed to determine other factors that
      influence specifically the solubilization of arsenic in the bioleaching system
      such as: pH, dissolved oxygen concentration, redox potentials, nature of
      concentrate and temperature among others. At. ferrooxidans was able to completely
      oxidize the minerals present during the arsenic bioleaching. Other elements
      present originally in the concentrate such as Zn, Sb, and Cu were also
      solubilized. The process of bioleaching is expected to be influenced by
      mechanisms that still need to be established due to the diversity of the minerals
      involved and by the presence of traces of metals in the concentrate. The increase
      in pulp density generates a decrease in the dissolved arsenic concentration. This
      decrease is greater in runs where air was not injected to the system. The maximum
      rate of arsenic dissolution in the concentrate was found using; small surface
      area of particle exposure, low pulp density, injecting air and adding 9 K medium
      to the system. The effect of addition of ferric chloride during the arsenic
      bioleaching resulted in a decrease of the solubilized arsenic in the system. The
      presence of CO2 is associated to the decrease in arsenic dissolution.

PMID- 15482596
TI  - Mothers' education but not fathers' education, household assets or land ownership
      is the best predictor of child health inequalities in rural Uganda.
AB  - BACKGROUND: Health and nutrition inequality is a result of a complex web of
      factors that include socio-economic inequalities. Various socio-economic
      indicators exist however some do not accurately predict inequalities in children.
      Others are not intervention feasible. OBJECTIVE: To examine the association of
      four socio-economic indicators namely: mothers' education, fathers' education,
      household asset index, and land ownership with growth stunting, which is used as
      a proxy for health and nutrition inequalities among infants and young children.
      METHODS: This was a cross-sectional survey conducted in the rural district of
      Hoima, Uganda. Two-stage cluster sampling design was used to obtain 720
      child/mother pairs. Information on indicators of household socio-economic status
      and child anthropometry was gathered by administering a structured questionnaire
      to mothers in their home settings. Regression modelling was used to determine the
      association of socio-economic indicators with stunting. RESULTS: One hundred
      seventy two (25%) of the studied children were stunted, of which 105 (61%) were
      boys (p < 0.001). Bivariate analysis indicated a higher prevalence of stunting
      among children of: non-educated mothers compared to mothers educated above
      primary school (odds ratio (OR) 2.5, 95% confidence interval (CI) 1.4-4.4); non
      educated fathers compared to fathers educated above secondary school (OR 1.7, 95%
      CI 0.8-3.5); households belonging in the "poorest" quintile for the asset index
      compared to the "least poor" quintile (OR 2.1, 95% CI 1.2-3.7); Land ownership
      exhibited no differentials with stunting. Simultaneously adjusting all socio
      economic indicators in conditional regression analysis left mothers' education as
      the only independent predictor of stunting with children of non-educated mothers
      significantly more likely to be stunted compared to those of mothers educated
      above primary school (OR 2.1, 95% CI 1.1-3.9). More boys than girls were
      significantly stunted in poorer than wealthier socio-economic strata.
      CONCLUSIONS: Of four socio-economic indicators, mothers' education is the best
      predictor for health and nutrition inequalities among infants and young children
      in rural Uganda. This suggests a need for appropriate formal education of the
      girl child aimed at promoting child health and nutrition. The finding that boys
      are adversely affected by poverty more than their female counterparts
      corroborates evidence from previous studies.

PMID- 15482597
TI  - General practitioners believe that hypnotherapy could be a useful treatment for
      irritable bowel syndrome in primary care.
AB  - BACKGROUND: Irritable bowel syndrome is a common condition in general practice.
      It occurs in 10 to 20% of the population, but less than half seek medical
      assistance with the complaint. METHODS: A questionnaire was sent to the 406 GPs
      listed on the West Sussex Health Authority Medical List to investigate their
      views of this condition and whether they felt hypnotherapy had a place in its
      management RESULTS: 38% of general practitioners responded. The achieved sample
      shared the characteristics of target sample. Nearly half thought that irritable
      bowel syndrome (IBS) was a "nervous complaint" and used a combination of "the
      placebo effect of personal care," therapeutic, and dietary advice. There is
      considerable divergence in the perceived effectiveness of current approaches.
      Over 70% thought that hypnotherapy may have a role in the management of patients
      with IBS; though the majority (68%) felt that this should not be offered by
      general practitioners. 84% felt that this should be offered by qualified
      hypnotherapist, with 40% feeling that this should be offered outside the health
      service. CONCLUSIONS: General practitioners vary in their perceptions of what
      constitutes effective therapy in IBS. They are willing to consider referral to a
      qualified hypnotherapist.

PMID- 15482598
TI  - Activation of the hedgehog pathway in advanced prostate cancer.
AB  - BACKGROUND: The hedgehog pathway plays a critical role in the development of
      prostate. However, the role of the hedgehog pathway in prostate cancer is not
      clear. Prostate cancer is the second most prevalent cause of cancer death in
      American men. Therefore, identification of novel therapeutic targets for prostate
      cancer has significant clinical implications. RESULTS: Here we report that
      activation of the hedgehog pathway occurs frequently in advanced human prostate
      cancer. We find that high levels of hedgehog target genes, PTCH1 and hedgehog
      interacting protein (HIP), are detected in over 70% of prostate tumors with
      Gleason scores 8-10, but in only 22% of tumors with Gleason scores 3-6.
      Furthermore, four available metastatic tumors all have high expression of PTCH1
      and HIP. To identify the mechanism of the hedgehog signaling activation, we
      examine expression of Su(Fu) protein, a negative regulator of the hedgehog
      pathway. We find that Su(Fu) protein is undetectable in 11 of 27 PTCH1 positive
      tumors, two of them contain somatic loss-of-function mutations of Su(Fu).
      Furthermore, expression of sonic hedgehog protein is detected in majority of
      PTCH1 positive tumors (24 out of 27). High levels of hedgehog target genes are
      also detected in four prostate cancer cell lines (TSU, DU145, LN-Cap and PC3). We
      demonstrate that inhibition of hedgehog signaling by smoothened antagonist,
      cyclopamine, suppresses hedgehog signaling, down-regulates cell invasiveness and
      induces apoptosis. In addition, cancer cells expressing Gli1 under the CMV
      promoter are resistant to cyclopamine-mediated apoptosis. All these data suggest
      a significant role of the hedgehog pathway for cellular functions of prostate
      cancer cells. CONCLUSION: Our data indicate that activation of the hedgehog
      pathway, through loss of Su(Fu) or overexpression of sonic hedgehog, may involve
      tumor progression and metastases of prostate cancer. Thus, targeted inhibition of
      hedgehog signaling may have significant implications of prostate cancer
      therapeutics.

PMID- 15482599
TI  - Serum S100B in primary progressive multiple sclerosis patients treated with
      interferon-beta-1a.
AB  - S100B belongs to a family of calcium-binding proteins implicated in intracellular
      and extracellular regulatory activities. This study of serum S100B in primary
      progressive multiple sclerosis (PPMS) is based on data obtained from a
      randomized, controlled trial of Interferon beta-1a in subjects with PPMS. The key
      questions were whether S100B levels were associated with either disability or MRI
      findings in primary progressive MS and whether Interferon beta-1a has an effect
      on their S100B levels. Serial serum S100B levels were measured using an ELISA
      method. The results demonstrated that serum S100B is not related to either
      disease progression or MRI findings in subjects with primary progressive MS given
      Interferon beta-1a. Furthermore there is no correlation between S100B levels and
      the primary and secondary outcome measures.

PMID- 15482600
TI  - Appraising and applying evidence about a diagnostic test during a performance
      based assessment.
AB  - BACKGROUND: The practice of Evidence-based Medicine requires that clinicians
      assess the validity of published research and then apply the results to patient
      care. We wanted to assess whether our soon-to-graduate medical students could
      appraise and apply research about a diagnostic test within a clinical context and
      to compare our students with peers trained at other institutions. METHODS: 4th
      year medical students who previously had demonstrated competency at probability
      revision and just starting first-year Internal Medicine residents were used for
      this research. Following an encounter with a simulated patient, subjects
      critically appraised a paper about an applicable diagnostic test and revised the
      patient's pretest probability given the test result. RESULTS: The medical
      students and residents demonstrated similar skills at critical appraisal,
      correctly answering 4.7 and 4.9, respectively, of 6 questions (p = 0.67). Only
      one out of 28 (3%) medical students and none of the 15 residents were able to
      correctly complete the probability revision task (p = 1.00). CONCLUSIONS: This
      study found that most students completing medical school are able to appraise an
      article about a diagnostic test but few are able to apply the information from
      the article to a patient. These findings raise questions about the clinical
      usefulness of the EBM skills possessed by graduating medical students within the
      area of diagnostic testing.

PMID- 15482601
TI  - Review and standardization of cell phone exposure calculations using the SAM
      phantom and anatomically correct head models.
AB  - We reviewed articles using computational RF dosimetry to compare the Specific
      Anthropomorphic Mannequin (SAM) to anatomically correct models of the human head.
      Published conclusions based on such comparisons have varied widely. We looked for
      reasons that might cause apparently similar comparisons to produce dissimilar
      results. We also looked at the information needed to adequately compare the
      results of computational RF dosimetry studies. We concluded studies were not
      comparable because of differences in definitions, models, and methodology.
      Therefore we propose a protocol, developed by an IEEE standards group, as an
      initial step in alleviating this problem. The protocol calls for a benchmark
      validation study comparing the SAM phantom to two anatomically correct models of
      the human head. It also establishes common definitions and reporting requirements
      that will increase the comparability of all computational RF dosimetry studies of
      the human head.

PMID- 15482602
TI  - Elevated levels of matrix metalloprotein-3 in patients with coronary aneurysm: A
      case control study.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the
      pathogenesis of arterial aneurysms through increased proteolysis of extracellular
      matrix proteins. Increased proteolysis due to elevated matrix degrading enzyme
      activity in the arterial wall may act as a susceptibility factor for the
      development of coronary aneurysms. The aim of this study was to investigate the
      association between MMPs and presence of coronary aneurysms. METHODS: Thirty
      patients with aneurysmal coronary artery disease and stable angina were enrolled
      into study (Group 1). Fourteen coronary artery disease patients with stable
      angina were selected as control group (Group 2). MMP-1, MMP-3 and C-reactive
      protein (CRP) were measured in peripheral venous blood and matched between the
      groups. RESULTS: Serum MMP-3 level was higher in patients with aneurismal
      coronary artery disease compared to the control group (20.23 +/- 14.68 vs 11.45
      +/- 6.55 ng/ml, p = 0.039). Serum MMP-1 (13.63 +/- 7.73 vs 12.15 +/- 6.27 ng/ml,
      p = 0.52) and CRP levels (4.78 +/- 1.47 vs 4.05 +/- 1.53 mg/l, p = 0.13) were not
      significantly different between the groups. CONCLUSION: MMPs can cause arterial
      wall destruction. MMP-3 may play role in the pathogenesis of coronary aneurysm
      development through increased proteolysis of extracellular matrix proteins.

PMID- 15482604
TI  - Selected conference proceedings of the IV Barcelona International Congress on the
      Mediterranean Diet. March 6-7, 2002. Barcelona, Spain.

PMID- 15482603
TI  - Single photon emission computed tomography (SPECT) of anxiety disorders before
      and after treatment with citalopram.
AB  - BACKGROUND: Several studies have now examined the effects of selective serotonin
      reuptake inhibitor (SSRI) treatment on brain function in a variety of anxiety
      disorders including obsessive-compulsive disorder (OCD), posttraumatic stress
      disorder (PTSD), and social anxiety disorder (social phobia) (SAD). Regional
      changes in cerebral perfusion following SSRI treatment have been shown for all
      three disorders. The orbitofrontal cortex (OFC) (OCD), caudate (OCD), medial pre
      frontal/cingulate (OCD, SAD, PTSD), temporal (OCD, SAD, PTSD) and, thalamic
      regions (OCD, SAD) are some of those implicated. Some data also suggests that
      higher perfusion pre-treatment in the anterior cingulate (PTSD), OFC, caudate
      (OCD) and antero-lateral temporal region (SAD) predicts subsequent treatment
      response. This paper further examines the notion of overlap in the neurocircuitry
      of treatment and indeed treatment response across anxiety disorders with SSRI
      treatment. METHODS: Single photon emission computed tomography (SPECT) using Tc
      99 m HMPAO to assess brain perfusion was performed on subjects with OCD, PTSD,
      and SAD before and after 8 weeks (SAD) and 12 weeks (OCD and PTSD) treatment with
      the SSRI citalopram. Statistical parametric mapping (SPM) was used to compare
      scans (pre- vs post-medication, and responders vs non-responders) in the combined
      group of subjects. RESULTS: Citalopram treatment resulted in significant
      deactivation (p = 0.001) for the entire group in the superior (t = 4.78) and
      anterior (t = 4.04) cingulate, right thalamus (t = 4.66) and left hippocampus (t
      = 3.96). Deactivation (p = 0.001) within the left precentral (t = 4.26), right
      mid-frontal (t = 4.03), right inferior frontal (t = 3.99), left prefrontal (3.81)
      and right precuneus (t= 3.85) was more marked in treatment responders. No pattern
      of baseline activation distinguished responders from non-responders to subsequent
      pharmacotherapy. CONCLUSIONS: Although each of the anxiety disorders may be
      mediated by different neurocircuits, there is some overlap in the functional
      neuro-anatomy of their response to SSRI treatment. The current data are
      consistent with previous work demonstrating the importance of limbic circuits in
      this spectrum of disorders. These play a crucial role in cognitive-affective
      processing, are innervated by serotonergic neurons, and changes in their activity
      during serotonergic pharmacotherapy seem crucial.

PMID- 15482605
TI  - Out of the box. Experience of food, from observation and reflection, and with all
      the senses.

PMID- 15482606
TI  - Do childhood growth indicators in developing countries cluster? Implications for
      intervention strategies.
AB  - OBJECTIVE: The effectiveness of geographic targeting in nutrition programmes
      depends largely on the degree to which malnutrition clusters within particular
      areas. This study investigates the extent to which the childhood nutrition
      indicators, stunting (height-for-age Z-score <-2) and wasting (weight-for-height
      Z-score <-2), are spatially clustered; this information is used to determine the
      implications of spatial clustering for the effectiveness of geographic targeting.
      DESIGN: Analysis of data from Demographic and Health Survey (DHS) results.
      Clustering is assessed by calculating intra-cluster correlation coefficients
      (ICCs). Estimating the proportion of malnourished children covered by a programme
      successfully targeting 10% of clusters with the highest malnutrition prevalences
      allows an assessment of the effectiveness of geographic targeting. SETTING: Fifty
      eight DHS III (1992-1997) and DHS IV (1998-2001) reports from 46 developing
      countries. SUBJECTS: Pre-school children of mothers interviewed by DHS. MAIN
      RESULTS: The extent of clustering of nutritional status was surprisingly low
      (median ICC for national samples: stunting=0.054, wasting=0.032) and most
      countries were characterised by having an ICC <0.1--i.e. low clustering--for
      childhood undernutrition (91% of countries for wasting and 78% for stunting). Our
      assessment of the effectiveness of geographic targeting showed that coverage was
      better for wasting than for stunting; for wasting, 23% of countries would achieve
      less than 20% coverage, compared with 76% of countries achieving less than 20%
      coverage for stunting. Coverage is dependent on the overall prevalence of
      malnutrition and the ICC. CONCLUSIONS: Childhood nutritional status is determined
      at the household, or even individual, level; nutrition programmes that are
      geographically targeted may result in high levels of under-coverage and leakage,
      thereby compromising their cost-effectiveness; the lack of clustering questions
      the appropriateness of current nutrition interventions.

PMID- 15482607
TI  - Secular and socio-economic trends in compliance with dietary targets in the north
      Glasgow MONICA population surveys 1986-1995: did social gradients widen?
AB  - OBJECTIVE: To compare trends in the consumption of key foods over 10 years in the
      most deprived and least deprived quarters in north Glasgow, Scotland as defined
      by the Carstairs deprivation index for their postcode of domicile. DESIGN: Four
      random, cross-sectional, age- and gender-stratified population surveys carried
      out in 1986, 1989, 1992 and 1995. After assigning a deprivation score, food
      frequency questionnaires from 2883 men and 3127 women were examined for
      compliance with dietary targets, examining trends by gender and within the most
      and least deprived quarters of the population. SETTING: North Glasgow, Scotland.
      SUBJECTS: Over 600 men and 600 women (aged 25-64 years) in each of the four
      survey years who completed a lifestyle questionnaire including a food frequency
      section. RESULTS: Increasing trends in the reported consumption of fruit and
      vegetables and oil-rich fish were observed over the 10-year period. However, the
      trend to increased fruit and vegetable consumption in the most deprived groups
      was not significant, and in 1995 only 8% of men and 12% of women in this group
      claimed consumption of these foods 4 or more times a day. In general, a higher
      percentage of those in the least deprived group met the targets for the key
      foods. CONCLUSIONS: Trends to increasing consumption of fruit and vegetables and
      fish were in the right direction, but the targets for consumption of certain key
      foods were met by a minority of the population. The progress towards the target
      for fruit and vegetables showed widening social gradients with time.

PMID- 15482608
TI  - Low compliance with recommendations on folic acid use in relation to pregnancy:
      is there a need for fortification?
AB  - OBJECTIVE: As a means to prevent neural tube defects (NTDs), women planning
      pregnancy in Denmark are recommended to take a dietary supplement of 400 microg
      folic acid daily during the periconceptional period. We examined compliance with
      this recommendation in a national survey. DESIGN: Cohort study on pregnant women
      in Denmark. SETTING: The Danish National Birth Cohort (DNBC). SUBJECTS: From
      November 2000 to February 2002, 22,000 pregnant women were recruited for DNBC.
      Use of dietary supplements was recorded at enrollment. Compliance with the
      recommendation was related to an information campaign that took place during the
      second half of 2001, and to lifestyle factors provided in a telephone interview
      by the end of the first trimester of pregnancy. RESULTS: An increase was seen in
      the proportion of women complying with the recommendation in the study period and
      this coincided with the information campaign events. However, even at the end of
      the period, only 22.3% of the women who had planned their pregnancy fully
      complied with the recommendation. No increase at all was seen in periconceptional
      folic acid use among women with unplanned pregnancies. Young age, low education
      and smoking were identified as factors that determined non-compliance.
      CONCLUSIONS: Alternative and more effective strategies are needed if the Danish
      population is to benefit fully from the knowledge that folic acid prevents NTDs.
      Future strategies should not only target vulnerable groups, such as the less
      educated and the young, but also women who get pregnant without planning this.
      The only possible way to reach the last group may be through fortification of
      foods with folic acid.

PMID- 15482609
TI  - Assessment of Turkish women's knowledge concerning folic acid and prevention of
      birth defects.
AB  - OBJECTIVES: In Turkey, the incidence of neural tube defects (NTDs) is 30.1 per
      10,000 births. For this reason it seems an important problem for women of
      childbearing age. Adequate periconceptional consumption of folic acid could
      prevent NTDs. Most women are unaware of this recommendation. The objectives of
      this study were to evaluate women' knowledge and beliefs with regard to folic
      acid, and to estimate the consumption frequency of vitamin supplements
      periconceptionally and during the first trimester of pregnancy. DESIGN: Eight
      hundred and eighteen married women who had delivered a live-born infant within
      the previous 12 months completed the questionnaire. Each subject participated in
      a 20-minute interview, with the questionnaire comprising multiple-choice
      statements. A random sample of 10 public health centres was drawn from 27 in
      three districts in Konya where about 50% of the population lives. RESULTS: Only
      22% of subjects had heard or read about folic acid. Thirteen per cent of women
      indicated knowledge of the direct link between folic acid supplementation and NTD
      prevention. The knowledge was greatest among 26- to 35-year-olds. Women with a
      university degree were more likely to have heard about folic acid than were less
      educated women. CONCLUSION: The results indicate that further government efforts
      are needed to inform the population and promote the optimal use of folic acid
      supplements and folate-enriched foods. It is the responsibility of national
      authorities to increase health education concerning folic acid and the prevention
      of NTDs in their countries.

PMID- 15482610
TI  - Factors associated with the initiation of breast-feeding by Aboriginal mothers in
      Perth.
AB  - OBJECTIVES: To identify the prevalence of breast-feeding at discharge and the
      determinants of breast-feeding initiation amongst Aboriginal women. DESIGN: A
      prospective cohort study using a self-administered baseline questionnaire and
      telephone-administered follow-up interviews. SETTING: Six hospitals with
      maternity wards in Perth, Western Australia. SUBJECTS: Four hundred and twenty
      five Aboriginal mothers of newborn infants. RESULTS: At discharge, 89.4% of
      Aboriginal mothers were breast-feeding. Breast-feeding at discharge was most
      positively associated with perceived paternal support of breast-feeding, with an
      adjusted odds ratio (OR) of 6.65 (95% confidence interval (CI) 2.81-15.74), and
      with maternal age (OR 1.12, 95% CI 1.03-1.22), but negatively associated with
      parity and having delivered vaginally. CONCLUSION: The factors independently
      associated with breast-feeding at discharge were similar to those previously
      identified for a group of non-Aboriginal Perth women, suggesting that separate
      breast-feeding interventions specially targeted at Aboriginal women are not
      warranted. The findings do, however, highlight the importance of including the
      father in the breast-feeding discussions.

PMID- 15482611
TI  - Dietary intake and body mass index in HIV-positive and HIV-negative drug abusers
      of Hispanic ethnicity.
AB  - OBJECTIVE: Malnutrition in drug abusers has been attributed to poor diet.
      However, previous studies are conflicting. Many studies have not considered
      possible concurrent HIV disease. The purpose of this study was to determine the
      relationship between drug abuse and dietary intake in Hispanic Americans with and
      without HIV infection. DESIGN: Dietary intake was measured using 3-day food
      records and 24-hour dietary recalls in three groups: HIV-positive drug abusers,
      HIV-negative drug abusers and HIV-positive persons who do not use drugs ('non
      drug abusers'). SETTING: The baseline data from a prospective cohort study of the
      role of drug abuse in HIV/AIDS weight loss and malnutrition conducted in Boston,
      Massachusetts, USA. SUBJECTS: The first 284 participants to enroll in the study.
      RESULTS: HIV-positive drug abusers had a body mass index (BMI) that was
      significantly lower than that of HIV-positive non-drug abusers. Reported energy,
      fat and fibre intakes did not differ between groups. All groups had median
      reported intakes of vitamin A, vitamin B6, vitamin B12, selenium and zinc that
      were in excess of the dietary reference values (DRI). Intakes of alpha-tocopherol
      were below the DRI, but did not differ from intakes of the general US population.
      However, increasing levels of drug abuse were associated with lower reported
      intakes of vitamin B6, vitamin B12, selenium and zinc. CONCLUSIONS: Overall, this
      study does not support the notion that dietary intake can explain the lower BMI
      of HIV-positive drug abusers. Further studies examining non-dietary determinants
      of nutritional status in drug abusers are warranted.

PMID- 15482612
TI  - The UK Women's Cohort Study: comparison of vegetarians, fish-eaters and meat
      eaters.
AB  - BACKGROUND: This paper describes the development of the UK Women's Cohort Study
      and presents cohort baseline characteristics. METHODS: In total, 35,372 women,
      aged 35-69 years at recruitment, were selected to ensure a wide range of dietary
      intakes. Diet was assessed by a 217-item food-frequency questionnaire (FFQ).
      Detailed lifestyle information was collected by postal questionnaire.
      Vegetarians, fish-eaters and meat-eaters were compared. RESULTS: The cohort women
      are mainly white, well-educated, middle-class and married with children. They are
      health-conscious with only 11% current smokers and 58% taking dietary
      supplements. Twenty-eight per cent of subjects self-report as being vegetarian
      and 1% as vegan. However, only 18% are defined as 'vegetarian' from the FFQ. Fat
      provides 32% of energy; vitamin and mineral intakes are high, with a broad range
      of intakes. Meat-eaters are older, with a higher body mass index (BMI) and the
      lowest intakes of carbohydrate, fibre, vitamin C, folate, iron and calcium. Other
      fish-eaters are similar to vegetarians. Vegetarians have the lowest intakes of
      protein, fat and saturated fat. Oily fish-eaters have the lowest BMI; are the
      least likely to smoke or use full-fat milk; and are the most likely to use
      dietary supplements and consume the most fruit and vegetables. Oily fish-eaters
      have the highest total energy intake and vegetarians the lowest. Semi-skimmed
      milk, bread, potatoes, wine, bananas and muesli are important contributors to
      energy for all groups. CONCLUSION: A large cohort of middle-aged women has been
      created encompassing a wide range of different eating patterns, including diets
      currently of interest to research into protection against cancer and coronary
      heart disease. Participants will be followed up to study the effects of different
      food and nutrient intakes on long-term health outcomes.

PMID- 15482613
TI  - High alcohol consumption in Germany: results of the German National Health
      Interview and Examination Survey 1998.
AB  - OBJECTIVE: To analyse the alcohol consumption behaviour of the German adult
      population, with a focus on the characteristics of persons drinking more than the
      tolerable upper alcohol intake level (TUAL) of 10-12 g day(-1) for healthy adult
      women and 20-24 g day(-1) for healthy adult men. DESIGN AND SETTING: For the
      German National Health Interview and Examination Survey 1998, a representative
      sample of free-living adults was drawn. A total of 7124 participants were
      interviewed comprehensively about their sociodemographic background, lifestyle
      and eating habits including alcohol consumption. SUBJECTS: A sub-sample of 4030
      women and men, 18-79 years old, who were involved in the integrated German
      Nutrition Survey. RESULTS: About 16% of women and 31% of men had mean alcohol
      consumption above the TUAL. Among other factors, the inclination to exceed the
      TUAL was related to middle-age, high socio-economic status, smoking and use of
      soft drugs. Among both women and men, a high proportion of persons drinking above
      the TUAL was observed among those consuming low amounts of soft drinks, fruit,
      poultry, milk products, bread and cake/biscuits. Women preferred to drink wine,
      whereas men preferred to drink beer. CONCLUSIONS: Many Germans have an alcohol
      consumption level above the TUAL and thus are supposed to be at increased risk
      for alcohol-associated diseases.

PMID- 15482614
TI  - The association of diet and other lifestyle factors with the onset of overactive
      bladder: a longitudinal study in men.
AB  - OBJECTIVE: To investigate associations between diet and non-dietary lifestyle
      factors and the onset of overactive bladder (OAB) in men. SUBJECTS: Random sample
      of community-dwelling men aged 40 years plus. DESIGN AND METHODS: Baseline data
      on urinary symptoms and diet were collected from 5454 men using a postal
      questionnaire and a food-frequency questionnaire. Follow-up data on urinary
      symptoms were collected from 4887 men in a postal survey one year later. Logistic
      regression analysis was used to investigate diet and lifestyle factors associated
      with onset of OAB in the men without OAB at baseline. RESULTS: There was a highly
      significant negative association between beer intake at baseline and subsequent
      OAB onset (P=0.001), with reduced risk at all levels of intake compared with
      those who seldom/never drank beer. Adjustment for total alcohol intake (g ethanol
      day(-1)) reduced the significance of the association (P=0.02). None of the food
      groups studied was associated with OAB onset, with the possible exception of
      potatoes (P=0.05), which showed an increased risk of onset at the highest level
      of consumption. Physical activity, smoking and obesity were not significantly
      associated. CONCLUSIONS: While most diet and lifestyle factors were not
      associated with OAB onset, the evidence from this prospective longitudinal study
      suggests that beer may have a protective role in the development of OAB. This
      could be due to a non-alcoholic ingredient as well as the alcohol content.

PMID- 15482615
TI  - A Monte Carlo simulation to validate the EAR cut-point method for assessing the
      prevalence of nutrient inadequacy at the population level.
AB  - OBJECTIVE: The aim of this study was to validate the EAR cut-point method for
      assessing the prevalence of nutrient inadequacy at the population level. DESIGN
      AND SUBJECTS: Different methods for estimating the prevalence of inadequate
      intake were compared: the cut-off point method, with cut-off points at the
      Recommended Dietary Allowance (RDA), 0.66 RDA, 0.50 RDA and the Estimated Average
      Requirement (EAR); the probability approach; and a Monte Carlo simulation. In
      total, 591 men and 674 women, aged 20-55 years, were included in the analyses.
      RESULTS: The prevalence of inadequate intake as estimated by the EAR cut-point
      method was similar to the prevalence of inadequacy estimated by both
      probabilistic methods. The cut-point method with RDA, 0.66 RDA and 0.50 RDA as
      cut-off limits induced an over- or an underestimation of the real prevalence of
      inadequacy. CONCLUSIONS: Probabilistic methods consider both the intake
      variability and the requirement variability, and, as a result, their estimation
      should be closer to the real prevalence of inadequacy. The use of the EAR cut
      point method yields a good estimation of the prevalence of inadequate intake,
      comparable to the probability approach, and limits over- and underestimation of
      the prevalence induced by other cut-off points.

PMID- 15482616
TI  - Effects of revision of Japanese food composition tables on estimation of nutrient
      intakes, with reference to age-dependent differences.
AB  - OBJECTIVE: To identify effects of revision of the Japanese food composition
      tables from the fourth version to the fifth version on nutrient intake
      estimation. DESIGN: A database on 783 samples of 24-hour food duplicate portions
      was re-visited. Nutrients in the duplicate portions were estimated by use of the
      fourth and fifth versions of the Japanese food composition tables in parallel,
      together with supplemental use of other databases. The two sets of estimates were
      subjected to comparison. SETTING: The sample collection was conducted at 31 sites
      all over Japan. SUBJECTS: The sample donors were 783 women aged 20-78 years.
      RESULTS: Compared with the estimates by use of the fourth version of the tables,
      the estimates by the fifth version were substantially higher for intakes of
      energy, carbohydrate, dietary fibre, vitamin A and niacin, and lower for iron
      intake. The increase in carbohydrate intake estimates was more evident in older
      women than in young women, whereas the decrease in the intake estimation of iron
      and the increase in that of dietary fibre were more marked in young women than in
      older women. CONCLUSION: The recent revision of food composition tables in Japan
      induced substantial changes in the estimation of nutrient intakes, i.e. an
      increase in energy, carbohydrate, dietary fibre, vitamin A and niacin, and a
      decrease in iron. The extent of the changes varied depending on age.

PMID- 15482617
TI  - Underreporting of energy intake among Japanese women aged 18-20 years and its
      association with reported nutrient and food group intakes.
AB  - OBJECTIVES: To evaluate the ratio of energy intake to basal metabolic rate
      (EI/BMR) among young female Japanese adults, and to compare the lifestyle and
      dietary characteristics between relatively low and high reporters. DESIGN:
      Dietary intakes were assessed over a 1-month period with a validated, self
      administered, diet history questionnaire, and lifestyle variables were assessed
      by a second questionnaire designed for this survey. The ratio of EI/BMR was
      calculated from reported energy intake and estimated basal metabolic rate.
      SUBJECTS: In total, 1889 female Japanese university students aged 18-20 years who
      were enrolled in dietetics courses. RESULTS: Ninety-five per cent of the subjects
      were classified into a non-obese group (body mass index (BMI) <25 kg m(-2);
      mean+/-standard deviation (SD): 20.8+/-2.6 kg m(-2)). EI/BMR was 1.43+/-0.40
      (mean+/-SD). Sixty-eight per cent of the subjects showed an EI/BMR level below
      the possibly balanced value of 1.56, 37% showed EI/BMR below the minimum survival
      value of 1.27 and 2% of the subjects showed EI/BMR exceeding the maximum value
      for a sustainable lifestyle of 2.4. BMI, body weight and BMR decreased
      significantly with the increase in EI/BMR (P<0.001). The percentage of energy
      from carbohydrate was significantly higher, whereas those from fat and protein
      were significantly lower, among the lower EI/BMR groups. As for food groups, a
      significantly declining trend from the lowest to the highest EI/BMR groups was
      observed for cereals. CONCLUSION: Underreporting, rather than overreporting, of
      energy intake was predominant in this relatively lean Japanese female population.
      BMI was the most important factor affecting the reporting accuracy of energy
      intake.

PMID- 15482618
TI  - Analysis of herbal teas made from the leaves of comfrey (Symphytum officinale):
      reduction of N-oxides results in order of magnitude increases in the measurable
      concentration of pyrrolizidine alkaloids.
AB  - OBJECTIVES: To determine the relative quantities of two hepatotoxic pyrrolizidine
      alkaloids, symphytine and echimidine, in teas prepared from comfrey leaves
      (Symphytum officinale), and to determine the potential contribution of the N
      oxide forms of these alkaloids to levels of the parent alkaloids. DESIGN: Comfrey
      leaves were purchased from three commercial sources and used to prepare tea in a
      manner consistent with the methods used by consumers. An extraction scheme was
      devised for extraction of the alkaloids, and a gas chromatographic method was
      developed to quantify the two major alkaloids, symphytine and echimidine.
      Recognising that the N-oxide derivatives of these alkaloids have also been
      identified in comfrey preparations, chemical reduction was applied to determine
      the total quantities of the alkaloids as free bases and as N-oxide derivatives.
      RESULTS: The concentration of symphytine and echimidine varied considerably
      between teas prepared from leaves purchased from the different vendors of plant
      material. Moreover, a much higher concentration of symphytine was found in the
      tea when steps were included to reduce N-oxides prior to analysis. The treatment
      of pure symphytine with hot water did not generate the N-oxide derivative de
      novo. CONCLUSIONS: Since the pyrrolizidine alkaloids are known to be hepatotoxic,
      consumption of herbal teas made from comfrey leaves may be ill-advised. The
      concentration of pyrrolizidine alkaloids in such teas may be underestimated
      substantially unless the concentration of N-oxides is taken into consideration.

PMID- 15482619
TI  - Does the definition of the Mediterranean diet need to be updated?

PMID- 15482620
TI  - Food, youth and the Mediterranean diet in Spain. Development of KIDMED,
      Mediterranean Diet Quality Index in children and adolescents.
AB  - OBJECTIVE: To evaluate dietary habits in Spanish children and adolescents based
      on a Mediterranean Diet Quality Index tool, which considers certain principles
      sustaining and challenging traditional healthy Mediterranean dietary patterns.
      DESIGN: Observational population-based cross-sectional study. A 16-item
      Mediterranean Diet Quality Index was included in data gathered for the EnKid
      study (in which two 24-hour recalls, a quantitative 169-item food-frequency
      questionnaire and a general questionnaire about socio-economic, demographic and
      lifestyle items were administered). SETTING: Spain. SUBJECTS: In total, 3850
      children and youths aged 2-24 years residing in Spain. RESULTS: Of the sample,
      4.2% showed very low KIDMED index results, 49.4% had intermediate values and
      46.4% had high index results. Important geographical differences were seen, with
      subjects from the Northeast showing the most favourable outcomes (52% with
      elevated scores vs. 37.5% of those from the North). Lower percentages of high
      diet quality were observed in low socio-economic groups, compared with middle and
      upper income cohorts (42.8%, 47.6% and 54.9%, respectively). Large cities had
      more positive results and only slight variations were seen for gender and age.
      CONCLUSIONS: The KIDMED index, the first to evaluate the adequacy of
      Mediterranean dietary patterns in children and youth, confirms that this
      collective is undergoing important changes, which makes them a priority target
      for nutrition interventions. Results challenge certain commonly perceived notions
      tied to income level, population size and diet quality.

PMID- 15482621
TI  - Mediterranean Adequacy Index of Italian diets.
AB  - OBJECTIVE: To assess, particularly in longitudinal studies, how close or far the
      food intakes of population groups are from a reference dietary pattern. DESIGN:
      Computation of an index, called the Mediterranean Adequacy Index (MAI), by
      dividing the sum of the percentage of total energy from typical Mediterranean
      food groups by the sum of the percentage of total energy from non-typical
      Mediterranean food groups. The reference Italian-Mediterranean diet utilised was
      that of subjects from Nicotera in 1960. SETTING: Different areas in Italy.
      SUBJECTS: Men aged 45-65 years at the start of the study from rural areas of
      Italy in the Seven Countries Study followed for 26 years (Crevalcore and
      Montegiorgio), elderly men and women from Perugia followed for 11 years, men and
      women from Pollica (Salerno) followed for 32 years, and families from Rofrano
      (Salerno) followed for 41 years. RESULTS: The median value of MAI among 40-59
      year-old men from Nicotera in 1960 was 7.2; in Crevalcore it was 2.9 in 1965 and
      2.2 in 1991; and in Montegiorgio, 5.6 in 1965 and 3.9 in 1991. In Pollica, the
      values in men ranged from 5.6 to 6.3 in 1967 and from 2.4 to 4.5 in 1999; for
      women, the corresponding ranges were 4.2-7.2 and 2.7-4.1. In elderly men of
      Perugia, median MAI value was 4.9 in 1976 and 3.2 in 1987; for women, the
      corresponding values were 3.1 and 2.6. CONCLUSIONS: The diet of these Italian
      population groups has changed over the last four decades, progressively
      abandoning the nutritional characteristics of the reference Italian-Mediterranean
      diet. The MAI proposed is simple to compute; it has satisfactory discriminating
      power particularly for longitudinal dietary data with only a few limitations.

PMID- 15482622
TI  - Traditional Mediterranean diet and longevity in the elderly: a review.
AB  - OBJECTIVE: To review the evidence that the traditional Mediterranean diet is
      associated with longevity. SETTING: Elderly persons of both genders in Greece,
      Spain, Denmark and Australia studied by different groups of investigators.
      METHODS: Adherence to the principles of the Mediterranean diet was
      operationalised through a score devised a priori, and study participants were
      followed up until death or the end of the study. Proportional hazard models were
      used. RESULTS: Closer adherence to the Mediterranean diet was associated with a
      significant decrease in general mortality among the elderly persons studied.
      CONCLUSION: The Mediterranean diet is positively associated with longevity among
      the elderly. If the assumption holds that there is no interaction between age and
      diet with respect to general mortality, it can be inferred that the traditional
      Mediterranean diet represents a healthy nutritional pattern.

PMID- 15482623
TI  - Mediterranean diet and overall mortality differences in the European Union.
AB  - OBJECTIVE: To assess whether the Mediterranean diet contributes to overall
      mortality differences and trends between Mediterranean and non-Mediterranean
      European Union (EU) countries. DESIGN: Routinely recorded adjusted overall
      mortality and food availability data in Mediterranean and non-Mediterranean EU
      countries. A Mediterranean diet score designed a priori was used as instrument.
      SETTING: Fifteen EU countries in the 1960s and the 1990s. SUBJECTS: The general
      population in the 15 EU countries. RESULTS: The difference between Mediterranean
      and non-Mediterranean EU countries in a 7-point Mediterranean diet score was
      reduced from 2.9 in the 1960s to 1.6 in the 1990s. This reduction may underlie
      the reduction in the difference in general mortality between these countries,
      from about 100 deaths per 100,000 person-years in the early 1970s to about 50
      deaths per 100,000 person-years in the 1990s. CONCLUSIONS: The decline in overall
      mortality in the 15 EU countries over the last 25 years is probably unrelated to
      diet. However, the gradual loss of the survival advantage of Mediterranean EU
      citizens, compared with other EU citizens, may be linked to the gradual
      abandonment by the former of their dietary traditions.

PMID- 15482624
TI  - Ageing and the Mediterranean diet: a review of the role of dietary fats.
AB  - Consumers are becoming increasingly aware of the relationship between food and
      health. Concerns have been raised about dietary fats and their relative
      nutritional advantages or disadvantages. In investigations of the associations
      between health and fat intake, special emphasis has been placed on the benefits
      of virgin olive oil for counteracting certain neurodegenerative diseases and
      ageing. With respect to ageing, accumulating evidence indicates that an
      improvement in quality of life can be reached by modulation of the extrinsic
      factors that influence many ageing processes. Of the modifiable factors,
      nutrition appears to be one of the strongest elements known to influence the rate
      of ageing as well as the incidence of age-associated diseases such as
      atherosclerosis and neurodegenerative pathologies. This paper reviews the theory
      of ageing and the role of fatty acids in the mechanisms affecting its evolution.
      It also confirms that virgin olive oil, an essential component of the
      Mediterranean diet, provides large amounts of stable and not easily oxidizable
      fatty acids as well as remarkable quantities of powerful antioxidant molecules.

PMID- 15482625
TI  - Mediterranean diet and cognitive decline.
AB  - OBJECTIVE: To investigate the possible role of diet in age-related cognitive
      decline (ARCD) and cognitive impairment of both degenerative (Alzheimer's
      disease, AD) and vascular (vascular dementia, VaD) origin. DESIGN: Literature
      review. RESULTS: In an elderly population of southern Italy with a typical
      Mediterranean diet, high energy intake of monounsaturated fatty acids (MUFA)
      appeared to be associated with a high level of protection against ARCD. In
      addition, dietary fat and energy in the elderly seem to be risk factors, while
      fish consumption and cereals are found to reduce the prevalence of AD in European
      and North American countries. Finally, the relative risk of dementia (AD and VaD)
      was lower in the subjects of a French cohort who drank three or four glasses of
      red wine each day compared with total abstainers. CONCLUSION: Essential
      components of the Mediterranean diet--MUFA, cereals and wine--seem to be
      protective against cognitive decline. As such, dietary antioxidants and
      supplements, specific macronutrients of the Mediterranean diet, oestrogens and
      anti-inflammatory drugs may act synergistically with other protective factors,
      opening up new therapeutic interventions for cognitive decline.

PMID- 15482626
TI  - Mediterranean diet and cancer.
AB  - OBJECTIVE: To analyse the role of various aspects of the Mediterranean diet in
      several common epithelial cancers, including digestive and selected non-digestive
      tract neoplasms. DESIGN: Systematic analysis of data from a series of case
      control studies. SETTING: Northern Italy, between 1983 and 1998. SUBJECTS: Over
      12,000 cases of 20 cancer sites and 10,000 controls. RESULTS: For most epithelial
      cancers, the risk decreased with increasing vegetable and fruit consumption, with
      relative risk (RR) between 0.3 and 0.7 for the highest versus the lowest tertile.
      For digestive tract cancers, population-attributable risks for low intake of
      vegetables and fruit ranged between 15 and 40%. A protective effect was observed
      also for breast, female genital tract, urinary tract and a few other epithelial
      neoplasms. A number of antioxidants and other micronutrients showed an inverse
      relationship with cancer risk, but the main components responsible for the
      favourable effect of a diet rich in vegetables and fruit remain undefined. Fish
      tended to be another favourable diet indicator. In contrast, subjects reporting
      frequent red meat intake showed RRs above unity for several common neoplasms.
      Intake of whole-grain foods was related to a reduced risk of several types of
      cancer, particularly of the upper digestive tract. This may be due to a
      favourable role of fibre, but the issue is still open to discussion. In contrast,
      refined grain intake and, consequently, glycaemic load and glycaemic index were
      associated with increased risk of different types of cancer including, among
      others, breast and colorectal. CONCLUSIONS: A low-risk diet for cancer in the
      Mediterranean would imply increasing the consumption of fruit and vegetables, as
      well as avoiding increasing the intakes of meat and refined carbohydrates.
      Further, olive oil and other unsaturated fats, which are also typical aspects of
      the Mediterranean diet, should be preferred to saturated ones.

PMID- 15482627
TI  - Nutrition education and Mediterranean diet: exploring the teaching process of a
      school-based nutrition and media education project in Cretan primary schools.
AB  - BACKGROUND: During the past few decades there has been a gradual abandoning of
      the traditional Mediterranean diet by the population of Crete and especially
      among the younger generations. Since this is related to the rapidly increasing
      morbidity and mortality rates from chronic diseases, the need for educating young
      people on the principles of good nutrition becomes increasingly important. It is
      also acknowledged that the epidemiological field needs to focus on studying the
      implementation process, since this will allow for a deeper understanding of the
      outcomes. OBJECTIVES: The aims of the present study were to explore the process
      of implementing an innovation in Cretan primary schools and to identify best
      teaching practices and principles. DESIGN: In three state primary schools on the
      island of Crete, 107 children took part in a 30-h nutrition and media education
      programme. Classroom observations were used to define attitudes towards the
      programme and teaching methods. Besides baseline and post evaluation, the pupils
      were also interviewed about 11 months after the end of the programme.
      IMPLEMENTATION: During observation of the teaching process, emerging issues were
      the teacher's motivation and interest in the course, his/her preparation before
      each class, teaching ability and communication skills, the respect and discipline
      he/she kept and the innovative teaching methods used. In some cases researcher
      intervention in the classroom could not be avoided. FINDINGS AND CONCLUSIONS:
      Overall, individual teacher willingness and teaching skills were mainly
      responsible for the quality of teaching, the variety of educational methods used
      in classrooms and pupils' interest in the course. Changes in pupils' knowledge
      and recall of the course were related to teacher enthusiasm but also to
      researcher intervention. Exploring the teaching and learning process allowed a
      deeper understanding of the data. It is concluded that attempts to introduce the
      principles of a Mediterranean diet to children through nutrition education
      require innovative, enthusiastic and highly motivated teachers.

PMID- 15482628
TI  - Globalisation and income growth promote the Mediterranean diet.
AB  - OBJECTIVE: To examine global food demand patterns and how changing diets may
      stimulate demand for and trade of Mediterranean diet products. DESIGN: Literature
      review. Trends in global and US food consumption patterns are examined and trade
      data are reviewed to evaluate the impact of changing diets on trade of
      Mediterranean diet products. Market access issues are also addressed briefly to
      highlight the role of policy in the trade of Mediterranean diet products.
      RESULTS: Diets are shifting towards higher-value products such as meats, fruits
      and vegetables, and a wider array of packaged food products. Trade in these
      products has also grown in the past two decades, with several non-traditional
      importers and exporters becoming increasingly active in the global market.
      CONCLUSIONS: Income-driven demands for quality and variety are likely to increase
      the demand for Mediterranean diet products globally. While the middle-income
      countries appear to be the best growth prospects, the USA remains a potential
      growth market if these products can meet the growing consumer demand for variety,
      quality and convenience. Although consumer trends globally indicate growth in
      demand for Mediterranean diet products, the additional demand may not be
      reflected by a corresponding growth in trade. Trade in Mediterranean diet
      products continues to be hampered by higher than average trade barriers and high
      transportation costs for perishables.

PMID- 15482629
TI  - Serotonergic antidepressant effects on aggressive, self-injurious and
      destructive/disruptive behaviours in intellectually disabled adults: a
      retrospective, open-label, naturalistic trial.
AB  - There is a growing body of evidence that serotonergic antidepressants are useful
      in the treatment of maladaptive behaviours in the intellectually disabled.
      However, not all studies have shown positive results due to lack of efficacy,
      tolerance development, and troublesome side-effects. The current study consisted
      of a review of the treatment response to a variety of serotonergic
      antidepressants, consisting of selective serotonin reuptake inhibitors (SSRIs )
      (n = 36) and clomipramine (n = 2) in 38 institutionalized intellectually disabled
      adults (20 males, 18 females; mean age 45.6 yr, age range 18-74 yr). Those
      studied were treated for aggression, self-injurious behaviours,
      destructive/disruptive behaviours, depression/dysphoria, or a combination of
      these or other challenging behaviours. Most were receiving concurrent
      psychotropic and/or anticonvulsant medications. Effectiveness was determined by a
      retrospective review of the summaries of multidisciplinary Neuropsychiatric
      Behavioural Reviews (NBRs) in which global and specific maladaptive behaviours
      were rated on a 1- to 7-point scale, and by psychologists' ratings of target
      behaviours. Overall, statistically significant decreases in the ratings of global
      maladaptive behaviour and aggression, self-injurious behaviour,
      destruction/disruption and depression/dysphoria and in psychologists' ratings
      occurred in the subject group after the initiation of antidepressants. The
      results suggest that serotonergic antidepressants are useful in the treatment of
      challenging/maladaptive behaviours in the intellectually disabled.

PMID- 15482630
TI  - On the simulation of the time-course of dopamine D2 receptor occupancy from the
      pharmacokinetics of antipsychotics.

PMID- 15482631
TI  - Half-life of receptor occupancy--a meaningless concept.

PMID- 15482633
TI  - Can endogenous stem cells be stimulated to repair the degenerating brain?

PMID- 15482632
TI  - The many faces of fatigue in major depressive disorder.
AB  - Fatigue is a common complaint in the community and medical care settings.
      Different studies show a high comorbidity between fatigue and depressive
      disorder. Furthermore, fatigue is an important somatic symptom of depressive
      disorder and one of the main depressive presentations in primary-care medicine.
      Fatigue shows a slow response to antidepressant treatment and psychotherapy.
      Improved work performance is strongly correlated to improvement in energy.
      However, the assessment and treatment of fatigue in depressive disorder remains
      understudied. Different definitions of fatigue in depressive disorder are applied
      in DSM-IV and ICD-10, and depression rating scales all show a different coverage
      of this core depressive symptom, thereby hampering scientific research.
      Serotonin, norepinephrine, dopamine and histamine mediate symptoms of fatigue in
      depressive disorder. Although few data address the effect of antidepressants or
      augmentation strategies on fatigue-related symptoms, there is a pharmacological
      rationale for using antidepressant monotherapies, such as venlafaxine, bupropion,
      sertraline, fluoxetine, or augmentation of first-line treatment with stimulants
      or modafinil.

PMID- 15482634
TI  - Nasal administration of albuterol: an alternative route of delivery.
AB  - The use of metered-dose inhalers for the delivery of albuterol, a beta2-selective
      adrenergic agonist, is associated with drawbacks, especially in children and the
      elderly. This investigation was designed to assess the effectiveness of albuterol
      delivered intranasally and to compare this delivery route with intratracheal and
      intravenous delivery. Three parameters of pulmonary function (peak maximal
      expiratory flow, maximal expiratory flow at 50% vital capacity, and total lung
      capacity) in anaesthetized, artificially ventilated guinea pigs were used to
      determine the degree of protection produced by albuterol against
      bronchoconstrictor responses provoked by acetylcholine. The heart rate was also
      measured. Although intranasal albuterol induced a slower protective action during
      the very initial phase of absorption, the drug was shown to be equally effective
      when administered either intranasally or intratracheally. In contrast, despite a
      significant effect initially in the case of intravenous albuterol, its ability to
      influence pulmonary function faded rather rapidly. No statistically significant
      differences in heart rate could be detected among the different treatment groups.
      In conclusion, intranasal albuterol may offer an alternative to metered-dose
      inhalers for the treatment of acute bronchospasm and for prevention of exercise
      induced asthma, especially for children and the elderly.

PMID- 15482635
TI  - Encapsulation of naturally occurring flavonoids into liposomes: physicochemical
      properties and biological activity against human cancer cell lines.
AB  - Liposomes consisting of egg phosphatidylcholine were prepared by a thin-film
      hydration method followed by sonication and were used to investigate the
      percentage encapsulation of four flavonoids (quercetin, rutin, isoscutellarein
      and isoscutellarein diglycoside). The lipid recovery and the flavonoid-to-lipid
      molar ratio were measured using high-performance thin-layer chromatography/flame
      ionization detection and UV-vis spectroscopy. Differential scanning calorimetry
      was used to study the effect of the flavonoids on the phase transition
      temperature and on the enthalpy of the main phase transition of
      dipalmitoylphosphatidylcholine bilayers, and their ability to influence the
      membrane fluidity. The final liposomal formulation incorporating flavonoids, as
      well as free flavonoids, were tested for their activity against human cancer cell
      lines using the sulforhodamine B assay. The results showed that the encapsulation
      efficiency varied from 95% (0.21 flavonoid-to-lipid molar ratio) to 37.5% (0.09
      flavonoid-to-lipid molar ratio) for isoscutellarein and its glycoside,
      respectively. The differential scanning calorimetry data showed close thermal and
      dynamic effects depending on the structure of the flavonoids, and suggest that
      there is a relationship between flavonoid molecular structure and the interaction
      with model membranes. Liposomal isoscutellarein showed improved growth inhibiting
      activity against all cell lines tested in comparison with that of its free form,
      which was inactive (>100 microM).

PMID- 15482636
TI  - Evaluation of in-vivo topical anti-inflammatory activity of indometacin from
      liposomal vesicles.
AB  - The aim of this study was to evaluate the in-vivo drug release profile of
      indometacin-loaded liposomes into the skin. Large unilamellar vesicles (LUVs),
      composed of dipalmitoyl-L-alpha-phosphatidylcholine and cholesterol (9:1), were
      obtained using the extrusion method and then incorporated in hydrogels (LUV-A and
      LUV-B). The delivery of indometacin from the liposomal system was evaluated by
      determining its in-vivo local anti-inflammatory activity after cutaneous
      application of liposomal gel formulations; the anti-inflammatory activity is
      directly proportional to the amount of drug that actually crosses the skin. UVB
      induced erythema on healthy human volunteers was chosen as the inflammatory model
      and the extent of erythema was monitored by the non-invasive technique of
      reflectance spectrophotometry. The results showed that LUV dispersions containing
      indometacin provided a high percentage of entrapped drug (approximately 84%).
      Furthermore, in-vivo findings revealed that the anti-inflammatory effect was more
      prolonged when indometacin was delivered from a liposomal gel formulation rather
      than from a gel formulation without liposomes. In particular, the indometacin
      loaded gel formulation LUV-A showed a sustained effect, probably related to an
      interaction between LUV lipids and stratum corneum lipid structure. This
      interaction produces a depot in the stratum corneum that ensures sustained
      release of the drug to deeper skin layers.

PMID- 15482637
TI  - Pluronic block copolymers and Pluronic poly(acrylic acid) microgels in oral
      delivery of megestrol acetate.
AB  - Several Pluronic-based formulations were studied in-vitro and in a rat model with
      respect to the release and bioavailability of megestrol acetate (MA) after oral
      administration. It was demonstrated that an aqueous, micellar formulation
      comprising a mixture of a hydrophobic (L61) and a hydrophilic (F127) Pluronic
      copolymer, significantly enhanced the bioavailability of MA administered orally
      at relatively low doses (1-7 mg kg(-1)). Pluronic-based microgels (spherical gel
      particles of sub-millimetre size) were introduced as MA vehicles. The microgels
      comprised a cross-linked network of poly(acrylic acid) onto which the Pluronic
      chains were covalently attached. Microgels of Pluronic L92 and poly(acrylic acid)
      fabricated into tablet dosage forms exhibited dramatically lowered MA initial
      burst release. The MA release was pH-dependent owing to the pH sensitivity of the
      microgel swelling, with the drug retained by the microgel at pH 1.8 and released
      slowly at pH 6.8. In the rat model, a significant increase in MA bioavailability
      was observed when the microgel-formulated MA was administered orally at a high
      dose of 10 mg kg(-1), owing to the enhanced retention of the microgel. The study
      of the microgel passage through the gastrointestinal tract demonstrated the
      microgel retention characteristic of a very high molecular weight polymer and the
      absence of any systemic absorption of the polymer.

PMID- 15482638
TI  - Development of a single-dose stabilized poly(D,L-lactic-co-glycolic acid)
      microspheres-based vaccine against hepatitis B.
AB  - The purpose of this study was to develop a stable single-dose vaccine based on
      recombinant hepatitis B surface antigen (HBsAg) in poly(D,L-lactic-co-glycolic
      acid) (PLGA) microspheres, in which HBsAg was stabilized by a protein stabilizer
      (trehalose) and an antacid (Mg(OH)2). The microspheres were prepared by the
      double emulsion method and characterized by scanning electron microscopy. To
      neutralize the acids liberated by the biodegradable lactic/glycolic acid based
      polymer, we coincorporated into the polymer an antacid, Mg(OH)2, which
      neutralized the acidity during degradation of the polymer and also prevented
      HBsAg structural losses and aggregation. The antigen integrity after
      encapsulation was examined by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis followed by silver staining, isoelectric focusing and Western
      blotting techniques, which confirmed that antigen remained intact after
      encapsulation. In-vitro release experiments were performed in phosphate-buffered
      saline (pH 7.4) and the release of antigen was found to be improved by the
      protein stabilizer (trehalose). In stability studies, performed at 37 degrees C,
      the microspheres were found to be stable for 16 days. The immunogenicity of
      stable microsphere formulations bearing HBsAg was compared with the conventional
      alum-absorbed HBsAg vaccine in a guinea-pig model. The antibody titre indicated
      that a single injection of stabilized HBsAg-PLGA microspheres produced a better
      immune response than two injections of alum-formulated HBsAg vaccine. The
      findings suggest that recombinant HBsAg can be stabilized by use of a protein
      stabilizer and antacid during entrapment, and this stabilized preparation can be
      useful for antigen delivery.

PMID- 15482639
TI  - An ocular drug delivery system containing zinc diethyldithiocarbamate and
      HPbetaCD inclusion complex--corneal permeability, anti-cataract effects and
      mechanism studies.
AB  - Our purpose was to study the formulation and anti-cataract effects of aqueous eye
      drops containing a high concentration of zinc diethyldithiocarbamate (Zn-DDC). A
      possible mechanism of the anti-cataract effect of Zn-DDC was also studied. Zn-DDC
      and hydroxypropyl-beta-cyclodextrin (HPbetaCD) inclusion complex (Zn
      DDC/HPbetaCD) was studied using the saturation solution method and characterized
      by differential scanning calorimetry (DSC) and Fourier transform infrared
      spectroscopy (IR). Suitable formulations for Zn-DDC eye drops were established by
      means of in-vitro trans-corneal penetration experiments. The anti-cataract effect
      of the selected formulation was demonstrated by the delay in lens opacity
      development in hereditary shumuya cataract rats (SCRs). Semiquantitative reverse
      transcription polymerase chain reaction (RT-PCR) was performed to study the
      effect of diethyldithiocarbamate (DDC), a metabolite of Zn-DDC, on the
      transcription inducible nitric oxide synthase (iNOS) mRNA in human lens
      epithelial cells (HLEC). In the presence of 22% (w/v) HPbetaCD, the solubility of
      Zn-DDC in water (0.2 mM) was increased almost 850 fold (to 17 mM), by the
      formation of Zn-DDC/HPbetaCD. The stoichiometry of Zn-DDC inclusion was 1:1. The
      Zn-DDC/HPbetaCD stability constant, Ks (1:1) was estimated to be 3453 M(-1). The
      ophthalmic preparation containing 0.1% HPMC and 0.1% poloxamer 188 (P188)
      exhibited better permeability than the others in-vitro, and significantly delayed
      cataract formation in SCRs compared with non-treated SCRs. DDC inhibits the
      transcription of iNOS mRNA in HLEC. We concluded that this drug delivery system
      increases both the drug solubility in aqueous eye drops and the permeability of
      drug through the rabbit cornea, by the formation of a drug-cyclodextrin inclusion
      complex and the addition of polymers and penetration enhancers. The preparation
      effectively prevented the development of cataracts in SCRs. DDC, the metabolite
      of Zn-DDC, may be one of the factors in the prevention of cataract formation
      because it inhibits the transcription of iNOS mRNA.

PMID- 15482640
TI  - Decrease in oral bioavailability of ciclosporin by intravenous pulse of
      methylprednisolone succinate in rats.
AB  - We examined the effects of high-dose methylprednisolone on the bioavailability of
      orally administered ciclosporin in rats. To emulate the clinical protocol of
      methylprednisolone pulse therapy, methylprednisolone sodium succinate (MPS), a
      prodrug of methylprednisolone, was intravenously administered as repeated doses
      (66.3 mg kg(-1)) for 3 days. The area under the blood ciclosporin concentration
      versus time curve after oral administration was significantly reduced by 60% by
      pulse treatment with MPS. Based on our previous finding that the total body
      clearance of ciclosporin was reduced by about 20% by the same methylprednisolone
      pulse protocol, the extent of reduction in the oral bioavailability of
      ciclosporin was estimated to be approximately 50%, indicating a drug interaction
      between high-dose methylprednisolone and orally administered ciclosporin, which
      affected the absorption process. In rats treated with MPS, an in-situ efflux
      experiment using rhodamine-123 demonstrated that the reverse transport function
      of P-glycoprotein (P-gp) in the small intestine was significantly enhanced,
      although there was no significant increase in the intestinal microsomal activity
      of triazolam alpha- and 4-hydroxylation, metabolic probes for CYP3A. In addition,
      a significant decrease was observed in the amount of secreted bile acids serving
      as an enhancer of gastrointestinal absorption of ciclosporin in MPS treatment. To
      directly estimate the absorptive capacity, an in-situ absorption test was
      conducted using a closed-loop of small intestine in control and MPS-treated rats.
      Intestinal absorption of ciclosporin was significantly decreased, not only in the
      absence of bile flow but also by treatment with MPS, which well reflected the
      change in the in-vivo pharmacokinetic behaviour of ciclosporin after
      methylprednisolone pulsing. These results demonstrate that bioavailability of
      ciclosporin is markedly reduced by MPS pulse treatment, and the mechanism of this
      interaction was confirmed to involve enhancement of small-intestinal P-gp
      function and decrease in bile secretion.

PMID- 15482641
TI  - Cloned human 5-HT1A receptor pharmacology determined using agonist binding and
      measurement of cAMP accumulation.
AB  - Twenty agonists and nine antagonists were evaluated for their ability to compete
      for [3H]-8-hydroxy-2-(di-n-propylamino)tetralin ([3H]-8-OH-DPAT) binding to the
      cloned human serotonin-1A (ch-5-HT1A) receptor expressed in Chinese hamster ovary
      cells and for their ability to alter adenylyl cyclase activity in the same cells.
      The most potent full agonists of high affinity included N,N-dipropyl-5
      carboxamidotryptamine (pEC50=9.6 +/- 0.1), MDL 73005EF (pEC50=9.3 +/- 0.2), 5
      methyl-urapidil (pEC50=9.2 +/- 0.1), 5-carboxamidotryptamine (pEC50=9.1 +/- 0.2),
      R(+)-8-OH-DPAT (pEC50=8.6 +/- 0.1) and BMY-7378 (pEC50=8.6 +/- 0.1). WB-4101
      (pEC50=8.3 +/- 0.2; IA=79%), clozapine (pEC50=8.1 +/- 0.3; IA=29%), (buspirone
      (pEC50=7.6 +/- 0.2; IA=79%), quipazine (pEC50 <5; IA=45%) and R-DOI (pEC50 < 5;
      IA=31%) were weaker agonists with partial agonist properties. The most potent
      antagonists were WAY-100,635 (pKi=10.2 +/- 0.1), methiothepin (pKi=8.8 +/- 0.2),
      spiperone (pKi=8.7 +/- 0.2) and NAN-190 (pKi=8.5 +/- 0.2). The receptor
      affinities and functional potencies were well correlated (r=0.88; P <0.0001). Our
      binding data correlated well with the pharmacology of endogenous 5-HT1A receptors
      in the rabbit iris-ciliary body (r=0.91; P <0.001) and rat hippocampus (r=0.93, P
      <0.0001). Our functional cAMP data correlated well with other cAMP accumulation
      data (r=0.8, P <0.01 vs calf hippocampus) but less so with [35S]-GTPgammaS
      binding to the ch-5-HT(1A) receptor as a functional activity read-out (r=0.58, P
      <0.05). The present study provides a detailed pharmacological characterization of
      the ch-5-HT1A receptor using binding and functional assays.

PMID- 15482642
TI  - Asiatic acid derivatives enhance cognitive performance partly by improving
      acetylcholine synthesis.
AB  - Thirty-six semi-synthesized derivatives of asiatic acid were examined to
      determine if they had cognitive-enhancing activity in a passive avoidance test.
      Among the compounds tested, AS-2, AS-2-9-006 and AS-9-006 significantly
      alleviated scopolamine-induced memory impairment at doses of 1 and 10 mg kg(-1).
      Furthermore, AS-2 and AS-2-9-006 (1 mg kg(-1) administered four times daily)
      enhanced cognitive performance as determined in a water maze test. These three
      asiatic acid derivatives did not show any significant effect on the learning
      process in active avoidance tests. AS-2, AS-2-9-006 and AS-9-006 enhanced
      cholineacetyltransferase activity in a cholinergic neuroblastoma cell line, S
      20Y, in-vitro. Therefore, AS-2, AS-2-9-006 and AS-9-006 may have therapeutic
      value in alleviating certain memory impairment observed in dementia.

PMID- 15482643
TI  - Hyperici herba extract interaction with artificial lipid bilayers.
AB  - Hyperici herba (Hyp) is the aerial part collected during the flowering period
      from the well-known herb, Hypericum perforatum. Black lipid membrane experiments
      were performed to investigate the effect of the ethanolic Hyp extract on the
      electrical properties (capacitance and conductance) of artificial lipid bilayers.
      Hyp extract (1-10 microg mL(-1)) induced a concentration-dependent increase of
      both specific transmembrane capacitance and conductance in phosphatidylcholine
      (PC) membranes. The effect on conductance was enhanced when the Hyp extract (3
      microg mL(-1)) was present on both sides of the membrane (Gm=77.89 +/- 8.81 nS
      cm(-2), n=5) compared with single-sided application (Gm=36.48 +/- 2.41 nS cm(-2),
      n=5). In bilayers containing PC and phosphatidylserine (PS), PC:PS, the Hyp
      extract effect was greater than on pure PC bilayers, although the surface charge
      was not the determining factor of this enhanced activity. Adding cholesterol to
      the PC:PS mixture reverted the conductance increase induced by the Hyp extract in
      a dose-dependent manner. The specific pattern of the Hyp extract interaction with
      lipid bilayers has possible consequences concerning its absorption and
      bioavailability, as well as its pharmacodynamic effects on neuronal excitability.

PMID- 15482644
TI  - Modulatory effect of Morus indica against two-stage skin carcinogenesis in Swiss
      albino mice: possible mechanism by inhibiting aryl hydrocarbon hydroxylase.
AB  - The modulatory effect of the methanolic extract of Morus indica on 12-O
      tetradecanoyl-phorbol-13-acetate (TPA) induced oxidative stress and 7,12
      dimethylbenz(a)anthracene induced and croton oil (0.5% per mouse/0.2 mL acetone,
      v/v) promoted skin tumourigenesis in Swiss albino mice was studied. The efficacy
      of the M. indica extract was also evaluated in-vitro by studying the inhibition
      of the activity and level of aryl hydrocarbon hydroxylase, cytochrome P450, DNA
      sugar damage in calf thymus DNA and Fe(++)/ascorbate-induced lipid peroxidation
      in microsomes of mice. Significant increases in the activity of antioxidant
      enzymes (P <0.001) and a concomitant decrease (P <0.001) in the cutaneous
      malondialdehyde level were observed at three doses of plant extract (2.5, 5.0 and
      7.5 mg kg(-1)). Application of M. indica 1 h before each application of croton
      oil showed inhibitory effects on tumour promotion in terms of a reduction in the
      number of tumours/mouse and percentage of mice with tumours. It was also
      accompanied by an extension of the tumour latency period. TPA, which resulted in
      a rapid and transient stimulation of mouse epidermal ornithine decarboxylase
      activity (P <0.001), was inhibited dose dependently by pre-treatment with M.
      indica extract (P <0.001). The results suggest that M. indica extract may be
      useful as a therapeutic agent for cancer control as it blocks or suppresses
      events associated with chemical carcinogenesis.

PMID- 15482645
TI  - Protective effects of the Chinese prescription Hachimi-jio-gan against diabetic
      oxidative stress.
AB  - We used rats with streptozotocin (STZ)-induced diabetes to investigate the
      effects of Hachimi-jiogan on diabetic oxidative stress. Oral administration of
      Hachimi-jio-gan, at a dose of 50, 100 or 200 mg kg(-1) (body weight) daily, for
      10 days to rats with STZ-induced diabetes resulted in significant dose-dependent
      decreases in serum levels of glucose and glycosylated protein, implying that
      Hachimi-jio-gan improves the abnormal glucose metabolism that leads to oxidative
      stress. Hachimi-jio-gan also showed a tendency to reduce the urine volume and
      significantly reduced the elevated urinary protein level. Moreover, rats with STZ
      induced diabetes had high serum levels of superoxide and nitrite/nitrate.
      However, the administration of Hachimi-jio-gan dose-dependently reduced the
      overproduction of radicals associated with diabetes, suggesting the role of
      Hachimijio-gan as a radical scavenger that could protect against diabetic
      oxidative stress. Furthermore, thiobarbituric acid-reactive substance levels in
      serum and hepatic and renal mitochondria were dose-dependently lower in the
      Hachimi-jio-gan-treated groups than in the control diabetic group, which implies
      that Hachimi-jio-gan would alleviate the oxidative stress associated with
      diabetes through the inhibition of lipid peroxidation. These results indicate
      that Hachimi-jio-gan is a potential therapeutic agent that will reduce the damage
      caused by oxidative stress involved in diabetes.

PMID- 15482646
TI  - Reversal of cancer multidrug resistance by green tea polyphenols.
AB  - The aim of this study was to examine the effect and mechanism of green tea
      polyphenols (TP) on reversal of multidrug resistance (MDR) in a carcinoma cell
      line. Using the MTT assay, TP was examined for its modulating effects on the drug
      resistant KB-A-1 cells and drug-sensitive KB-3-1 cells. When 10 microg mL(-1) (-)
      epigallocatechin gallate (EGCG) or 40 microg mL(-1) TP were present
      simultaneously with doxorubicin (DOX), the IC50 of DOX on KB-A-1 cells decreased
      from 10.3 +/- 0.9 microg mL(-1) to 4.2 +/- 0.2 and 2.0 +/- 0.1 microg mL(-1),
      respectively. TP and EGCG enhanced the DOX cytotoxicity on KB-A-1 cells by 5.2-
      and 2.5-times, respectively, but did not show a modulating effect on KB-3-1
      cells. This indicated that both TP and EGCG had reversal effects on the MDR
      phenotype in-vitro. A KB-A-1 cell xenograft model was established, and the effect
      of TP on reversing MDR in-vivo was determined. Mechanistic experiments were
      conducted to examine the uptake, efflux and accumulation of DOX. Cloning and
      expression of the nucleotide binding domain of the human MDR1 gene in Escherichia
      coli was established, and by using colorimetry to examine the activity of ATPase
      to hydrolyse ATP, the ATPase activity of target nucleotide binding domain protein
      was determined. TP exerted its reversal effects through the inhibition of ATPase
      activity, influencing the function of P-glycoprotein, and causing a decreased
      extrusion of anticancer drug and an increased accumulation of anticancer drug in
      drug resistant cells. Using reverse transcription-polymerase chain reaction, the
      inhibitory effect of TP on MDR1 gene expression was investigated. Down-regulation
      of MDR1 gene expression was the main effect, which resulted in the reversal
      effect of TP on the MDR phenotype. TP is a potent MDR modulator with potential in
      the treatment of P-glycoprotein mediated MDR cancers.

PMID- 15482648
TI  - Inhibition of vascular smooth muscle cell migration by serum from rats treated
      orally with Saiko-ka-Ryukotsu-Borei-To, a traditional Chinese formulation.
AB  - Oral administration of Saiko-ka-Ryukotsu-Borei-To (SRB), a traditional Chinese
      formulation, has been found to prevent intimal thickening of the carotid artery
      after balloon endothelial denudation in cholesterol-fed rats. To clarify the
      mechanism of this effect, the present study investigated if SRB inhibits vascular
      smooth muscle cell (VSMC) migration, which plays an important role in the
      development of intimal thickening after endothelial injury. The serum (SRB serum)
      sampled from cholesterol-fed rats treated orally with SRB for 3 days before and 4
      days after the injury dose-dependently inhibited the migration of cultured VSMCs.
      When added directly to cultured VSMCs, the SRB extract did not inhibit VSMC
      migration. It is remarkable that SRB serum, which may contain a much lower
      concentration of SRB ingredients compared with the SRB extract, inhibited
      cultured VSMC migration. The present testing system using serum obtained from
      animals treated orally with traditional Chinese formulations may be useful for
      clarifying the pharmacological efficacy of such drugs, including many non
      absorbable components. Furthermore, it may be useful in the search for new active
      compounds in serum after oral administration of traditional Chinese formulations,
      the active metabolites of which have not been identified.

PMID- 15482647
TI  - Peroxynitrite scavenging mode of alaternin isolated from Cassia tora.
AB  - Peroxynitrite (ONOO-), formed from the reaction of superoxide (.O2-) and nitric
      oxide (NO), is a potent oxidant that contributes to the oxidation of various
      cellular constituents, including lipids, amino acids, sulfhydryls and
      nucleotides. It can cause cellular injury, such as DNA fragmentation and
      apoptotic cell death. ONOO- toxicity is also reported to be involved in
      inflammatory and neurodegenerative diseases, such as Alzheimer's disease,
      Parkinson's disease and atherosclerosis. Moreover, the necessity for a strong
      ONOO- scavenger is important because of the lack of endogenous enzymes that
      protect against the damage caused by ONOO-. The aim of this study was to evaluate
      the ability of natural products to scavenge ONOO-. We tested various plant
      extracts for their ONOO- scavenging activity. Among them, extract from Cassia
      tora, which is well known as an oriental herb in traditional medicine, showed
      potent ONOO- scavenging activity. Further analysis identified the phenolic active
      components, alaternin and nor-rubrofusarin glucose, as potent ONOO- scavengers.
      Spectrophotometric analysis demonstrated that alaternin and nor-rubrofusarin
      glucose led to a decrease in the ONOO- -mediated nitration of tyrosine through
      electron donation. In bovine serum albumin, alaternin, but not nor-rubrofusarin
      glucose, showed significant inhibition of ONOO- -mediated nitration in a dose
      dependent manner. We believe alaternin can be developed as an effective ONOO-
      scavenger for the prevention of ONOO- -associated diseases.

PMID- 15482649
TI  - Degradation of berenil (diminazene aceturate) in acidic aqueous solution.
AB  - The trypanocide berenil was assessed for chemical stability over the pH range 1-8
      at 37 degrees C and 0.2 M ionic strength. It was found to be sufficiently
      unstable under acid conditions that its therapeutic efficacy is most likely
      severely compromised when administered orally. At pH 3, the half-life was 35 min,
      decreasing to 1.5 min at pH 1.75. Reaction rate constants were corrected for the
      effects of buffer catalysis and were found to range from 2.00 min(-1) at pH 1 to
      6.1 x 10(-6) min(-1) at pH 8. The pH-rate profile displayed a region (pH 1-4)
      where specific acid catalysis was dominant, followed by a transitional region (pH
      5-7), and finally a region (pH >7) where uncatalysed degradation was most
      important. It is recommended that berenil be enteric coated for formulations to
      be used in treating Third World parasitic diseases.

PMID- 15482650
TI  - Structure-activity relationship studies on chalcone derivatives: potent
      inhibition of platelet aggregation.
AB  - In an effort to develop potent antiplatelet agents with anti-inflammatory action,
      a novel series of anti-inflammatory chalcones was screened to evaluate their
      antiplatelet effects. Structure-activity relationships and mode of action were
      investigated and characterized. The antiplatelet effects of the chalcones on
      washed rabbit platelets and human platelet-rich plasma were evaluated.
      Arachidonic acid-induced platelet aggregation was potently inhibited by almost
      all the chalcone derivatives. Collagen-induced platelet aggregation was potently
      inhibited by all the chalcone derivatives at 300 microM, except for compound 4 at
      100 microM. Compounds 6, 7 and 9 significantly inhibited the aggregation of
      washed rabbit platelets induced by platelet-activating factor at 300 microM. Of
      the compounds tested in human platelet-rich plasma, compounds 2, 8 and 9 showed
      significant inhibition of secondary aggregation induced by adrenaline. It is
      concluded that the antiplatelet effect of 2, 8 and 9 is mainly owing to an
      inhibitory effect on thromboxane formation. The inhibitory effect of 6, 7 and 9
      on platelet aggregation induced by platelet-activating factor could be owing to a
      calcium antagonizing effect or inhibition of intracellular calcium mobilization.

PMID- 15482651
TI  - High altitude and blood pressure in children.
AB  - We aimed to evaluate the blood pressure of children who had similar demographic
      characteristics but lived at different altitudes. Blood pressure of the children
      attending primary schools in Izmir (sea level: n = 425) and Van (altitude: 1725
      m, n = 291) were measured by mercurial sphygmomanometer for this study. They were
      similar with respect to age, sex, weight, height, and BMI. Mean age of the
      children was 10.51 +/- 0.87 years (range: 9 to 12 years), and 358 (50 percent) of
      them were female. Mean systolic blood pressure was significantly higher in the
      children living in Van than in the children living in Izmir (104.72 +/- 11.2 vs.
      97.96 +/- 25.5 mmHg, respectively, p < .001). Similarly mean diastolic blood
      pressure was significantly higher in the children living in Van than in the
      children living in Izmir (63.98 +/- 9.3 vs. 59.91 +/- 10.0 mmHg, respectively, p
      < .001). When blood pressure was evaluated with regard to height percentile, the
      number of children with a blood pressure over 90 percentile were 19 (4.5 percent)
      and 48 (16.5 percent) for systolic blood pressure, and 25 (5.9 percent) and 37
      (12.7 percent) for diastolic blood pressure among the children living in Izmir
      and Van, respectively (p < .001). Systolic and diastolic blood pressures were
      found to increase in parallel to the increase in body mass index in children
      living in Van (r = 0.358, p < .001 and r = 0.235, p < .001, respectively).
      However, blood pressures were not correlated to body mass index in children
      living in Izmir. A difference of 1700 m in altitude was associated with higher
      systolic and diastolic blood pressure levels in children with similar demographic
      characteristics, and at this altitude, body mass index and blood pressure showed
      a positive correlation.

PMID- 15482652
TI  - Formulation and roentgenographic studies of naproxen-pectin-based matrix tablets
      for colon drug delivery.
AB  - A study has been carried out to assess the potential use of pectin in combination
      with two added hydrocolloids, i.e., hydroxy-propyl-methyl cellulose and
      hydroxyethyl cellulose in varied concentrations and coated with ethyl cellulose
      and cellulose acetate phthalate. The results of in vitro drug release showed that
      the matrix tablets prepared with pectin, hydroxy ethyl cellulose (20 percent)
      when coated with ethyl cellulose and cellulose acetate phthalate were found to be
      63.0 percent, 8.4 percent, and 4.5 percent, respectively, in after eight hours
      during drug release study period. These results were confirmed with the results
      of roentgenographic studies in nine healthy human volunteers to find the shape
      and integrity of the dosage form. The X-ray photographs revealed that the enteric
      coated tablet was visible only up to 5.5 hours and at the end of eighth hour, the
      photograph has not shown any presence of tablet indicating the loss of shape and
      size by the microflora present in the colon region. So, the results of in vitro
      and roentgenographic studies revealed that pectin, hydroxy ethyl cellulose (20
      percent) base coated with ethyl cellulose and cellulose acetate phthalate was
      found to be a promising carrier for naproxen to colon.

PMID- 15482653
TI  - How ultrasound first came to new England.
AB  - Diagnostic ultrasound came to Yale in the 1960s and was first developed in
      Glasgow and London. This story tells us that ultrasound was well-established in
      the Department of Obstetrics and Gynecology at Yale University School of Medicine
      in the Yale-New Haven Hospital by 1970. By then it had caught up with the
      pioneers in New York, Denver, and even Glasgow.

PMID- 15482654
TI  - Marie Curie Nobel Centenary.

PMID- 15482655
TI  - The public and private personae of women in science.

PMID- 15482656
TI  - The life and legacy of Marie Curie.
AB  - Marie Curie was a remarkable woman whose discoveries broke new ground in physics
      and chemistry and also opened the door for advances in engineering, biology, and
      medicine. She broke new ground for women in science: she was, for example, the
      first woman to receive a doctor of science degree in France, the first woman to
      win Nobel Prize, the first woman to lecture at the Sorbonne, the first person to
      win two Nobel Prizes, and the first Nobel Laureate whose child also won a Nobel
      Prize. Her life offers insights into the changing role of women in science and
      academia over the past century. It also offers examples of many ways in which
      scientists can, and should, work to improve the educational programs and career
      opportunities available to those who follow in their footsteps.

PMID- 15482657
TI  - Interpretation of some results from radiotherapy and an attempt to determine a
      rational treatment technique. 1906.

PMID- 15482659
TI  - [Make efforts to improve the level of rescue and treatment of pediatric patients
      with septic shock].

PMID- 15482658
TI  - Yale project for health action: AIDS education in South Africa.

PMID- 15482660
TI  - [Hypertrophic cardiomyopathy in a premature infant].

PMID- 15482661
TI  - [Effects of different doses of hydrocortisone on acute lung injury in rats with
      early septic shock induced by Escherichia coli].
AB  - OBJECTIVE: To observe the effects of different doses of hydrocortisone (HC) on
      acute lung injury (ALI) and inflammatory response in rats at early stage of
      septic shock induced by Escherichia coli and to investigate the possible
      mechanisms for such differences. METHODS: ALI model of early septic shock was
      induced in rats by two injections of Escherichia coli at 5 hours interval, with
      the first intraperitoneal injection of 6.50 x 10(10) cfu/kg and followed by an
      external jugular vein injection of 2.00 x 10(11) cfu/kg. Forty Wistar rats were
      randomly divided into the following five groups: normal control, ALI without HC
      treatment, high-dose HC (150 mg/kg), medium-dose HC (20 mg/kg) and low-dose HC (6
      mg/kg). Two hours after the treatment, the specimens were collected for
      histopathological examination and the biological indexes of lung injury were
      measured. The expressions of intercellular adhesion molecule-1 (ICAM-1) and
      glucocorticoid receptor (GR) in lung tissues were also investigated by
      immunohistochemical assays. RESULTS: The biological indexes of lung injury
      [wet/dry weight ratio (g/g), total protein concentration in bronchoalveolar
      lavage fluid (mg/L) and lung permeability index (10(-3))] in ALI group (4.76 +/-
      0.10, 278.96 +/- 60.45, 4.73 +/- 0.60) were significantly increased as compared
      to those in normal control group (4.10 +/- 0.07, 67.46 +/- 13.27, 1.12 +/- 0.15)
      (P < 0.05). The grades of ALI pathologic changes in ALI group (11.13 +/- 1.13)
      was significantly higher than that in the normal control group (0.50 +/- 0.53, P
      < 0.05). The ratio of expression area of ICAM-1 in ALI group (0.149 +/- 0.037)
      was significantly increased as compared to that in the normal control group
      (0.051 +/- 0.018) (P < 0.05). The ratio of expression area of GR all group (0.043
      +/- 0.037) was significantly decreased as compared to that in the normal Control
      group (0.124 +/- 9.040) (P < 0.05) After administration of HC, all the lung
      injury indexes, pathological grades and the ratios of expression area of ICAM-1
      and GR were significantly improved, with the most remarkable effects observed in
      the low-dose HC group. The expressions of ICAM-1 and GR showed a significantly
      negative linear correlation (r = 0.55, P < 0.0001). CONCLUSION: These results
      indicated that the low-dose HC treatment had the most remarkable effects of
      improving the biological indexes of lung injury, inflammatory mediators and
      pathological changes. These HC dose dependent therapeutic effects might be
      associated with the level of GR expression.

PMID- 15482662
TI  - [Changes of platelet endothelial cell adhesion molecule-1, tissue type
      plasminogen activator and plasminogen activator inhibitor-1 expression in the
      lung tissue of neonatal rats after intraperitoneal injection with
      lipopolysaccharide].
AB  - OBJECTIVE: To further explore the pathogenesis of neonatal acute lung injury and
      neonatal pulmonary hemorrhage by establishing the animal model of neonatal acute
      lung injury (ALI) and by investigating the changes of platelet endothelial cell
      adhesion molecule-1 (PECAM-1), tissue type plasminogen activator (t-PA) and
      plasminogen activator inhibitor-1 (PAI-1) in ALI. METHODS: Totally 88 neonatal
      rats which were divided into 8 groups randomly including one normal saline
      control group and 30 min, 1 h, 2 h, 4 h, 8 h, 16 h and 24 h post injection
      groups. The changes of lung pathology in newborn rats were observed at different
      time after LPS was injected intraperitoneally. The changes of PECAM-1 protein, t
      PA and PAI-1 mRNA expression were measured by immunohistochemistry and RT-PCR.
      RESULTS: The expression of PECAM-1 protein and mRNA was decreased and the lowest
      level was reached at 8 h and 16 h post injection, respectively. The average
      values were 95.1 +/- 9.76 and 0.861 +/- 0.016, respectively, which were
      significantly lower than those in the control group (129.5 +/- 6.15, 1.192 +/-
      0.035, P < 0.01). The expression of t-PA and PAI-1 mRNA was increased after LPS
      was injected. The highest level of t-PA mRNA expression was observed at 2 h after
      injection. The average value was 1.195 +/- 0.036, which was significantly higher
      than that in the control group (0.781 +/- 0.017, P < 0.01). The highest level of
      PAI-1 mRNA expression was observed at 2 h, 4 h and 8 h post injection. The
      average values were 1.178 +/- 0.069, 1.153 +/- 0.036 and 1.176 +/- 0.044,
      respectively, which was significantly higher than those of the control group
      (0.681 +/- 0.019, P < 0.01). CONCLUSIONS: The expression of PECAM-1 protein and
      mRNA was decreased after LPS injection, suggesting the disruption of the tissue
      protective mechanism; the expression of t-PA and PAI-1 mRNA was increased,
      indicating the presence of a hypercoagulability state. At the same time, the
      expression of t-PA mRNA was increased which caused the extra-cellular matrix
      degradation at the early phase after LPS injection. These three phenomena might
      be the contributory factors to pulmonary hemorrhage.

PMID- 15482663
TI  - [A case with neonatal Mur's hemolysis].

PMID- 15482664
TI  - [Significance of soluble intercellular adhesion molecule-1 and procalcitonin in
      diagnosis of neonatal septicemia].
AB  - OBJECTIVE: Neonatal septicemia is a critical disease in neonatal period. Its
      incidence among live births is between 1 per thousand and 8 per thousand.
      Mortality of neonatal septicemia may be as high as 50% for infants who are not
      treated. The early signs of septicemia in the newborn are generally nonspecific.
      Blood culture and the other clinical diagnostic measures are not sufficiently
      sensitive. The present study aimed at evaluating potential use of soluble
      intercellular adhesion molecule-1 (sICAM-1), procalcitonin (PCT) and C-reactive
      protein (CRP) in diagnosis of septicemia. METHODS: The experimental group
      consisted of 50 newborns with septicemia who were treated in Hebei Provincial
      Children's Hospital from April 1, 2002 to December 30, 2002. Thirty of the 50
      cases had positive blood culture. The control group included 35 healthy newborns.
      Fasting blood samples were taken for bacterial cultures and sICAM-1, CRP, PCT
      determination. PCT and CRP contents were determined immediately after the
      specimens were collected. Analyses of sICAM-1 were done after inclusion of the
      last patient. Serum was separated from each specimen and stored at -20 degrees C
      within 2 hours. The analyses of sICAM-1 were performed by ELISA technique. CRP
      was analyzed by immunoturbidimetry assay (ITA). Immunochromatographic test was
      performed for detection of PCT from 200 ul serum. SPSS 10.0 was used to process
      the data. P values < 0.05 was considered to be statistically significant. One way
      analysis of variance (ANOVA), multiple comparison, chi-square test, paired
      samples T test, linear correlation, Spearman correlation analysis, ROC curve were
      used for statistical analysis. The sensitivity, specificity, positive and
      negative predictive values, accuracy, Youden's index for sICAM-1, PCT, CRP and
      WBC count were calculated. These values were compared with each other. RESULTS:
      (1) The content of sICAM-1 in control group varied widely from 79 to 1252 ng/ml.
      Comparison of the data indicated that there was significant difference among the
      three groups in the content of sICAM-1, CRP and PCT (P < 0.05), but not in WBC
      count. These markers are considered positive if sICAM-1 >or= 300 ng/ml, CRP >or=
      8 mg/l, PCT >or= 2 ng/ml. Their sensitivity was higher than WBC (P < 0.05). Among
      these indices, PCT has the highest specificity (94.3%), positive predictive
      (95.6%), negative predictive (82.5%), accuracy (89.4%), and Youden's index
      (80.3%). (2) No significant difference was found in sICAM-1 between pre- and post
      treatment (P > 0.05); however, there was significant difference in CRP and PCT.
      (3) sICAM-1 was in direct proportion to CRP (r = 0.339,P < 0.01). PCT is
      correlated with sICAM-1, CRP (the spearman correlation coefficient 0.569, 0.482,
      P < 0.01). CONCLUSION: Different individual is in different immune status; The
      level of sICAM-1 is related with neonatal septicemia. sICAM-1 concentration may
      be used as a diagnostic tool with high sensitivity (85%) and moderate specificity
      (54.3%) in neonates suspected of infection. The sensitivity and specificity of
      CRP (>or= 8 mg/l) were accordingly 87.5% and 54.3%. WBC count had low sensitivity
      for diagnosis (30.0%); Among these indices, PCT had the highest specificity
      (94.3%), positive predictive (95.6%), negative predictive (82.5%) Values,
      accuracy (89.4%), Youden's index (80.3%); No correlation was found between sICAM
      1 concentration and their ages in day accordingly. CRP, PCT may be used to
      estimate the effect of therapy. The correlation of the infectious indices
      indicates that the body may mobilize many organs at the same time to resist the
      invasion of organism.

PMID- 15482665
TI  - [Effects of hydrocortisone on oxygen free radicals released by polymorphonuclear
      neutrophils in lipopolysaccharide-induced acute lung injury in mice].
AB  - BACKGROUND: Corticosteroid treatment of acute lung injury (ALI) and acute
      respiratory distress syndrome (ARDS) has been one of the most controversial
      clinical issues in critical care. Although the administration of high-dose
      corticosteroids does not benefit patients with early septic shock and ARDS,
      recent clinical trials have indicated that treatment with relatively low-dose
      corticosteroids (2 to 3 mg/kg/day of methylprednisolone or equivalent) may
      improve outcome when used for late ARDS or persistent septic shock. The
      underlying mechanism was not fully clarified. Whether the administration of
      corticosteroids can arrest neutrophil-driven organ injury once started remains to
      be elucidated. OBJECTIVE: To observe the effects of hydrocortisone (HC, 6 mg/kg)
      on oxygen free radicals (OFR) released by PMN and pulmonary pathological changes
      in rat ALI model induced by lipopolysaccharide (LPS), to investigate the possible
      mechanism through which corticosteroids exert protective effect on ALI. METHODS:
      A rat model of ALI was induced by peritoneal injection of 2 x 10(12) Escherichia
      coli/kg. Fifty-six rats were randomly divided into three groups: normal control
      group, LPS group and HC group (6 mg/kg). Samples were collected 2 h, 4 h and 6 h
      after giving LPS to LPS and HC group (6 h after giving normal saline in normal
      control group) to measure the level of OFR released by PMN using
      chemiluminescence method based on lumino, and to compae of pulmonary pathological
      changes among the three groups. RESULTS: Pathological examination with light
      microscope in LPS group showed thickened pulmonary interstitia, inflammatory cell
      infiltration, edema and hemorrhage, which were in accordance with the features of
      ALI. There were significant differences in the release of OFR by PMN among the
      three groups (P < 0.01). The level of OFR released by PMN in LPS group was
      significantly higher than that of the control group, and continued to increase
      during the observation period (2 - 6 h after LPS). The release of OFR by PMN in
      HC group was significantly suppressed as compared with LPS group, which was
      peaked at 4 h after LPS injection (to 98.2%); there were also significant
      differences in the grades of ALI pathologic changes among the three groups (P <
      0.01). The grades of ALI pathologic changes in LPS group were significantly
      increased when compared with the normal control group (P < 0.05) while
      significantly decreased in HC group as compared with LPS group (P < 0.05).
      CONCLUSION: It was demonstrated in the LPS induced ALI model that OFR might play
      an important role in onset of ALI. Intervening with HC (6 mg/kg) treatment could
      ameliorate the lung injury and exert significant and sustained suppression on the
      release of OFR by PMN, showing that HC has a protective effect on LPS induced ALI
      and its theraputic effect occurs possibly through suppression on the release of
      OFR by PMN.

PMID- 15482666
TI  - [Rapid diagnosis of neonatal sepsis by 16SrRNA genes PCR amplification and
      genechip hybridization].
AB  - OBJECTIVE: To explore a method for rapid diagnosis of sepsis in newborn infants.
      METHODS: (1) The primers and oligonucleotide probes were designed and synthesized
      based on the sequences of bacterial 16SrRNA gene. The gene chip was prepared
      through the probes printed onto special glass slides. The gene chip included 18
      special probes: universal probe 1, universal probe 2, Gram positive bacterial
      probe, Gram negative bacterial probe 1, Gram negative bacterial probe 2,
      Staphylococcus aureus, coagulase negative staphylococcus (CoNS) 1, CoNS 2,
      Escherichia coli, Hemophilus influenzae, Listeria monocytogenes, Streptococcus
      pneumoniae, Streptococcus agalactiae, Bacteroides fragilis, Bacillus,
      Meningococcus, Corynebacterium, Propionibacterium; (2) Blood specimens from 285
      cases of suspected septicemia were cultured and bacterial 16S rRNA gene was
      detected separately; DNA isolated from blood specimens and cerebrospinal fluid
      was amplified by PCR, and PCR products were hybridized with the probes on the
      gene chips. Hybridization results were scanned and read by laser-scanner.
      RESULTS: (1) Of the 285 cases, 17 were positive by PCR and the positive rate
      (5.96%) was significantly higher than that of blood culture (2.81%) (P < 0.01).
      When blood culture was taken as control, the sensitivity of PCR was 100% and
      Specificity was 96.75%, the index of accurate diagnosis was 0.968. (2) The 17
      specimens which showed positive results by PCR were further hybridized on the
      gene chip. All were positive by universal probes. Among all of them, 5 were
      positive by E. coli probe; 4 were positive by Staphylococcus epidermidis; two
      were positive by Bacillus and Propionibacterium probes, separately; 4 were
      positive by CoNS. The 8 specimens which showed positive results by both PCR and
      blood culture, the result of gene chip hybridization coincided with the result of
      blood culture. CONCLUSION: Detection of the bacterial 16SrRNA genes in clinical
      specimens by gene chip hybridization technology can diagnose neonatal septicemia
      rapidly. This method has higher sensitivity and specificity than blood culture or
      other methods and can provide a rapid way for the etiological diagnosis of
      neonatal septicemia. Therefore the genechip method may be valuable and practical
      in early diagnosis of neonatal septicemia.

PMID- 15482667
TI  - [Rapid diagnosis of common pathogenic bacteria infection in newborn infants by
      16SrDNA oligonucleotide array].
AB  - OBJECTIVE: The rapid identification of pathogenic bacteria is important for
      earlier effective patient management and antimicrobial therapy, especially for
      the infant patient, whose immunological system is not fully developed. However
      conventional microbiogical techniques of bacterial identification, culture and
      isolation of pathogenic bacteria, identification by biochemistry and serological
      assay, are time-consuming and require intensive labor. On the basis of special
      gene sequence, PCR provides simple and rapid way to identify bacteria. But it is
      difficult to identify all of bacteria species which are suspicious of pathogenic
      agents. Oligonucleotide arrays provide a powerful tool for parallel detection of
      target genes. The objective of this study was to test a reverse oligonucleotide
      assay, which hybridize with the PCR product of 16SrDNA using a pair of universal
      primers, to rapidly identify common infant pathogenic bacteria. METHODS: By
      comparison and analysis of the 16SrDNA sequences of common pathogenic bacteria, a
      region, which has numerous sequence variations and flanked by highly conserved
      sequences, was found. A pair of universal primers was designed according to its
      flanking conservative sequence, and a set of probes specially targeting to eight
      species of infant pathogenic bacteria, including staphylococcus aureus,
      Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus faecalis, Hemophilus
      influenzae, Enterobacter cloacae, Escherichia coli, and Acinetobacter
      baumannii,according to the variable sequences. The probes were fixed on the nylon
      membrane with positive electricity, and hybridized them with the products of PCR
      using the universal primers. RESULTS: The universal primers could amplify the
      target sequence from bacteria including the eight common infant pathogenic
      bacteria and Staphylococcus epidermidis, Enterobacter aerogenes, Streptococcus
      pneumoniae,beta-hemolytic streptococcus, Neisseria meningitides, Citrobacter
      freundii, Bacillus subtilis, and Salmonella infantis,but could not amplify
      rotavirus and human DNA as control. The results showed that the oligonucleotide
      array could specially hybridize with the eight bacteria to be examined and could
      not hybridize with other bacteria. The lowest concentration of DNA (product of
      PCR) for oligonucleotide array was about 25 ng/ml. The results proved that the
      probes are highly selective and the oligonucleotide arrays could parallelly
      detect the eight common infant pathogenic bacteria. The results suggested that
      the oligonucleotide array system was able to identify the eight common infant
      pathogenic bacteria from clinical specimens and the results were the same as
      identified by automated bacterial detection machine. From the further
      experiments, the oligonucleotide array system could directly diagnose the common
      infant pathogenic bacteria from the broths of samples culture. CONCLUSIONS:
      Despite limited number of identifiable bacteria and lack of information on
      antibiotic susceptibility of bacteria, the reverse oligonucleotide assay system,
      which contains amplification of the segment of 16rDNA from samples using the
      universal primers and parallel detection of PCR products using specific probes,
      is an effective method to rapidly identify the eight common infant pathogenic
      bacteria.

PMID- 15482668
TI  - [Progresses in studies on relative renal dysfunction in patients with severe
      sepsis and septic shock].

PMID- 15482669
TI  - [West Nile virus infection].

PMID- 15482670
TI  - [Role of carbon monoxide and nitric oxide as neurotransmitters in nervous system
      diseases].

PMID- 15482671
TI  - [Evaluation of clinical value of anorectal manometry for diagnosis of
      Hirschsprung's disease in neonate].
AB  - OBJECTIVE: Hirschsprung's disease (HD), one of the most common causes resulting
      in lower intestinal obstruction in children, is prone to be misdiagnosed or to be
      missed from diagnosis because of its atypical clinical symptoms and inconspicuous
      morphological findings by barium enema X-ray. Recently, this situation has been
      largely ameliorated by increased comprehension of anorectal kinetics and
      improvement of instrument for measurement of anorectal pressure. By now,
      anorectal manometry (ARMM) has been regarded as a routine means for functional
      assessment and diagnosis for anorectal disease. Nevertheless, the accuracy rate
      of diagnosis of HD in neonate by ARMM remains to be elucidated. In this study the
      clinical evaluation of anorectal manometry as an early diagnostic method for
      neonates with Hirschsprung's disease was appraised. METHODS: Forty-two HD
      patients defined by pathological study of rectal tissue obtained via rectal
      mucous membrane biopsy or operation were recruited in this study. ARMM was
      performed in liquid transmission using PC polygraph high rate gastrointestinal
      dynamical detection system (PC Polygraf HR, CTD-synectics, Sweden), with 4-lumen
      catheter with which a small 5-cm-long balloon was connected at the terminus. All
      children were positioned on their left side or back during the procedure and the
      pressure transducers were placed in the mid-axillary line level. The results of
      ARMM performed before operation or biopsy were compared with the results of
      barium enema X-ray testing. The decrease of internal anal sphincter pressure as
      rectoanal inhibitory reflex (RAIR) was measured based on the fluctuation curve of
      pressure detected. HD was defined when no decrease of anal catheter pressure was
      detected after insufflation (RAIR positive), and suspected HD state was assessed
      with the presentation of incomplete relaxation or positive/negative results
      coexisted (RAIR abnormal) in canal. RESULTS: Thirty patients (71.43%) were
      diagnosed as HD by ARMM including 18 patients who showed negative response to
      RAIR and 12 patients whose response was abnormal. While barium enema examinations
      were carried out in all the 45 patients, the results showed 5 HD patients and 14
      suspected HD patients, giving an overall diagnostic accuracy of 45.24%. There
      were also 16 patients with positive ARMM response and negative barium enema
      findings together, and 5 patients with negative ARMM results and positive barium
      enema findings at the same time. There was a significant difference between the
      two diagnostic methods (chi(m)(2) = 4.76, P < 0.05). CONCLUSION: Anorectal
      manometry seems to be a more reliable method for diagnosis of Hirschsprung's
      disease in neonate than barium enema X-ray. Because ARMM is a simple, safe and
      non-invasive method, it can be used as a screening test of choice in neonates
      with clinically suspected HD. But for final diagnosis, it is reasonable to
      combine ARMM with other diagnostic methods in HD patients.

PMID- 15482672
TI  - [Effect of chemical modification of grafts on the survival improvement post
      haploidentical bone marrow transplantation in mice].
AB  - OBJECTIVE: Human leukocyte antigen (HLA) haploidentical bone marrow is a
      potential source of donor to children for its availability. The drawback is
      deleterious graft versus host disease (GVHD) reaction post transplantation
      because of the incompatibility of HLA antigen expression between donors and
      recipients, in which donor T lymphocyte is stimulated to proliferate and
      differentiate. The methoxy polyethylene glycol (mPEG) is a kind of amphoteric
      compound without immunogenicity, which was used to modify various proteins
      covalently and to prepare the versatile blood type. If mPEG modification blocks
      the activation of T cells in grafts, GVHD reaction probably would become less
      serious and transplantation might become successful. The aim of this study was to
      verify the improvement of haploidentical bone marrow transplantation (BMT) in a
      murine model by using mPEG of certain concentration to modify the grafts.
      METHODS: Male BALB/c mice were chosen as the donor, and female CB(6)F(1) mice as
      the recipient. There were three groups of mPEG modification, non-modification and
      irradiation control, and 20 mice in each group. The modified and non-modified
      mixture of bone marrow and spleen cells (as T lymphocytes) were transplanted to
      haploidentical lethally irradiated CB(6)F(1) mice via the tail vein. After the
      transplant, the hematopoietic recovery, survival rate, acute graft versus host
      disease (aGVHD) and chromosomal karyotype were analyzed and compared with
      controls. RESULTS: Seventy-five percent (15/20) of mice survived in the group of
      mPEG modification, while only 40% (8/20) survived in the group without the
      modification (chi(2) = 5.01, P = 0.025). And 100% mice died in the group of the
      irradiation control within 2 weeks. The hematopoietic recovery in the group of
      mPEG modification was show n to be faster than that in the group without
      modification (P < 0.05). Histopathological examination of the skin, liver and
      intestine showed typical signs of aGVHD, but the GVHD grading in the group of
      modification was less severe. The recipient mice in both groups of
      transplantation surviving for more than 75 days showed complete donor-type
      implantation by the chimerism examination. CONCLUSION: The modification of grafts
      by mPEG could alleviate aGVHD and improve the survival rate of mice after the
      haploidentical bone marrow transplantation.

PMID- 15482673
TI  - [Changes of P-selectin and E-selectin in children with Kawasaki disease].
AB  - OBJECTIVE: Kawasaki disease (KD) is a kind of febrile disorder without definite
      etiology. The pathologic change of KD is characterized by nonspecific vasculitis,
      which mainly involves the coronary artery. Some patients may have coronary
      angioma formation, and some of them will result in the coronary narrowing or
      embolism. Notwithstanding that KD has been one of the most common causes for
      acquired heart diseases in childhood in addition to the rheumatic fever, the
      pathogenesis of the vascular damage remains unknown. This study was conducted to
      explore the pathophysiological role of cell adhesion molecules (P-selectin and E
      selectin) on the endothelial lesions in KD, and to look for the evidence of
      direct relationship between the plasma levels of soluble cell adhesion molecules
      (P- and E-selectin) and the incidence of the coronary artery lesion (CAL).
      METHODS: Soluble P-selectin (PS), E-selectin (ES), thromboxane-B(2)(TXB(2)), 6
      keto-PGF(1)alpha (6-KPGF(1)alpha) were measured in 36 patients with KD, 20
      patients with febrile disease and 30 healthy children by using double antibody
      sandwich enzyme linked immunosorbent assay (ELISA) and radioimmunoassay. Patients
      with KD were separated into acute phase group, subacute phase group, recovery
      phase group, coronary artery lesion group (CAL), non-coronary artery lesion group
      (NCAL), intravenous immunoglobulin (IVIG) effective group (body temperature back
      to normal after 48 hours of using IVIG), and IVIG ineffective group. RESULTS:
      Plasma PS and ES levels in the acute phase group [(211 +/- 28 and 186 +/- 14)
      ng/ml], subacute phase group [(238 +/- 27 and 151 +/- 13) ng/ml] and recovery
      phase group [(198 +/- 21 and 1008 +/- 9) ng/ml] were significantly higher than
      those in the healthy group [(102 +/- 36 and 72 +/- 10) ng/ml, P < 0.01]. The
      plasma PS levels remained higher after the treatment, but in IVIG effective
      group, the PS and ES levels declined significantly (P < 0.01) compared with those
      in acute phase group. Plasma PS and ES levels of CAL group [(281 +/- 78 and 210
      +/- 52) ng/ml] were significantly higher than those of NCAL group [(217 +/- 15
      and 108 +/- 10) ng/ml, P < 0.01]. In contrast to 1 week after the treatment, the
      PS and ES in IVIG effective group at the time point of 2 weeks after the
      treatment decreased more significantly (P < 0.01). While the PS and ES in IVIG
      ineffective group remained higher at the time point of 2 weeks after the
      treatment, which showed no significant difference compared with those 1 week
      after the treatment (P > 0.05). One week after the treatment, the PS levels of
      IVIG effective and ineffective groups did not descend, and there was no
      significant difference in PS between these two groups at this time point. Two
      weeks after the treatment, the PS and ES in IVIG ineffective group remained
      higher than those in IVIG effective group, and there was a significant difference
      between them. The peak level of PS appeared in the subacute phase. TXB(2) levels
      of KD in acute phase group increased markedly, which were significantly higher
      than those of healthy group [(345 +/- 127 and 190 +/- 69) ng/L, P < 0.01]. There
      was no significant difference between subacute phase group and healthy group. No
      significant difference was found between CAL group and NCAL group (P > 0.05). The
      levels of TXB(2) declined quickly after the treatment. The 6-KPGF(1)alpha level
      in KD of acute phase group, subacute phase group and recovery phase group [(7.1
      +/- 2.8, 10.8 +/- 3.7 and 11.3 +/- 4.0) ng/L, respectively] was significantly
      lower than that of healthy group [(17.7 +/- 5.8) ng/L, P < 0.01], and the levels
      did not recover to normal even 2 weeks after the treatment. There was no
      significant difference 6-KPGF(1)alpha levels between CAL group and NCAL group (P
      > 0.05). In the febrile group, PS and ES levels showed no significant differences
      compared with healthy children (P > 0.05). ES level of KD patients was
      significantly correlated with CRP levels (r = 0.79 P < 0.01). In febrile group,
      there was no significant correlation between ES and CRP. There was a significant
      correlation between PS and PLT levels in KD patients (r = 0.75 P < 0.01), and no
      significant correlation between PS and PLT levels in febrile patients.
      CONCLUSION: The increase of plasma PS and ES levels in KD acute phase and
      subacute phase might play an important role in the pathophysiology of the
      endothelial damage. E- and P-selectin may potentially be a predictor of CAL in
      patients with KD.

PMID- 15482674
TI  - [Clinical phenotype genotype correlation in children with hemoglobin H disease in
      Zhuhai area of China].
AB  - OBJECTIVE: Alpha-thalassemia is one of the most common monogene disorders in the
      world. Most frequently, it is caused by deletions of alpha-globin gene (-alpha or
      --), and less commonly resulted from the non-deletional mutation (alpha(T)alpha).
      Hemoglobin H (HbH) disease is the most severe type among survivors of alpha
      thalassemia. The clinical presentation of children with the disease was highly
      heterogeneous. The aim of this study was to investigate the effect of alpha
      globin genotypes in the children with HbH disease on predicting the phenotypic
      severity and to define the factors involved in the disease progress. METHODS:
      Forty-three children with the disease in Zhuhai area of Guangdong, China were
      examined by using established techniques to detect genotypes of alpha-globin and
      to determine all hematological parameters. All detailed clinical data of the
      cases were recorded. Then clinical and hematological findings, and the
      correlation with genotypes were evaluated. RESULTS: Six alpha-thalassemia
      mutations were detected and interacted to produce 5 HbH disease genotypes. Of
      these genotypes, -alpha(3.7)/--(SEA)(60%), -alpha(4.2)/--(SEA) (19%) and
      alpha(CS)alpha/--(SEA) (12%) HbH diseases were prevalent in the area. Compared
      with -alpha(3.7)/--(SEA) HbH disease, significantly lower red blood cell (RBC)
      count, hemoglobin (Hb), mean corpuscular hemoglobin (MCHC) and HbA(2) (P < 0.05,
      0.01, 0.01 and 0.01, respectively), and significantly higher mean corpuscular
      hemoglobin volume (MCV) and HbH levels (both P < 0.01), and more severe clinical
      phenotypes were found in the HbH disease with alpha(T)alpha/--(SEA) genotype.
      While the differences were much more significant when compared with -alpha(3.7)/-
      (SEA) then compared with -alpha(4.2)/--(SEA) not only in the hematological
      parameters, but also in the severity of clinical phenotypes. In addition, HbH
      levels showed anegatively correlation with the RBC count (r = -0.39, P < 0.01).
      CONCLUSION: The phenotypes of HbH disease may be mainly related to the underlying
      genotypes. The children with alpha(T)alpha/--(SEA) genotype presented with more
      severe hematological and clinical phenotypes followed by the -alpha(4.2)/--(SEA)
      and then -alpha(3.7)/--(SEA) genotypes. But phenotypic severity was not simply
      related to the degree of alpha-globin deficiency. HbH levels were found to
      exacerbate anemia. These data might provide comprehensive and very valuable and
      basic information for the management of HbH disease, genetic counseling and
      prenatal diagnosis.

PMID- 15482675
TI  - [In vitro antibacterial activity of cefdinir against isolates of respiratory
      tract pathogens in children].
AB  - OBJECTIVE: To study the in vitro antibacterial activity of cefdinir against
      clinical isolates of respiratory tract pathogens in Children. METHODS: MIC values
      of cefdinir against 380 strains were determined with E-test method and compared
      with those of cefaclor. RESULTS: All penicillin-susceptible Streptococcus
      pneumoniae (PSSP) strains were also susceptible to cefdinir and cefaclor. Both
      cefdinir and cefaclor were not active against penicillin-resistant SP (PRSP).
      Against penicillin-intermediate SP (PISP) the susceptibility rates of cefdinir
      and cefaclor were 70.1% and 57.4%, respectively. The activity of cefdinir and
      cefaclor against beta-lactamases negative Hemophilus influenzae (HI) was
      excellent, but the susceptibility rates of cefdinir and cefaclor against beta
      lactamases positive HI were 85.0% and 70.0%, respectively with MIC(90) of 1.5
      mg/L vs. 256.0 mg/L. Cefdinir presented higher activities and lower MIC values
      than cefaclor against Moraxella catarrhalis (MC), Group A streptococcus (GAS),
      methicillin susceptible staphylococcus aureus (MSSA), and extended spectrum beta
      lactamases (ESBLs) negative Escherichia coli (E. coli) or Klebsiella pneumoniae
      (K. pn). Both cefdinir and cefaclor were not susceptible to ESBLs positive E.
      coli and K. pn. CONCLUSIONS: Cefdinir exhibits excellent activity against PSSP,
      PISP, HI, as well as MC, GAS, MSSA and ESBLs negative E. coli or K. pn.

PMID- 15482676
TI  - [Role of the B lymphocytes in children with infectious mononucleosis caused by
      Epstein-Barr Virus].
AB  - OBJECTIVE: Infectious mononucleosis (IM) is a lymphoproliferative disease caused
      primarily by the Epstein-Barr virus (EBV) infection. The initial viral infection
      by EBV occurs in B lymphocytes and is followed by an extensive proliferation of T
      lymphocytes. Previous studies on immunity to EBV (including IM) have mainly
      focused on activation of peripheral blood T cells, which are responsible for the
      lymphocytosis in blood during acute IM. B cells, regarding CD23 as their
      activation marker, are the target cells of EBV infection. There are few reports
      on their effect in patients with IM. The role of them during acute IM is not
      known yet. The present study aimed to explore the action of B cells in patients
      with IM. METHODS: In a prospective trial, a group of subjects comprised 22
      patients with IM (14 boys and 8 girls) with mean age of 3.48 +/- 0.81 years
      (range 7 months to 8 years). Clinical diagnosis of IM was confirmed based on
      fever, lymphadenopathy, splenomegaly, lymphocytosis (> 50%), atypical lymphocytes
      (> 10%) in blood smears and the elevated levels of IgM antibody against EBV
      capsid antigen. The day of onset of fever was recognized as day 1 of illness.
      Blood samples taken during acute (3 - 5 days) and convalescent phase (about 15
      days) were analyzed for expressions of CD19, CD19(+)/CD23(+) on PBMC by flow
      cytometry (FCM) and was compared with those of control group. The number of the
      days with fever was recorded. RESULTS: (1) The levels of CD19 and CD19(+)/CD23(+)
      expressions were markedly decreased in acute stage [CD19 (5.63 +/- 2.91)%, (387
      +/- 178)/mm(3), CD19(+)/CD23(+) (2.45 +/- 1.87)%, (160 +/- 99)/mm(3)] and in
      convalescent stage [CD19 (12.49 +/- 5.70)%, (428 +/- 156)/mm(3), CD19(+)/CD23(+)
      (5.05 +/- 2.79)%, (172 +/- 78)/mm(3)] in patients with IM as compared with those
      of the healthy controls [CD19 (16.20 +/- 2.80)%, (545 +/- 150)/mm(3);
      CD19(+)/CD23(+) (7.08 +/- 2.78)%, (249 +/- 136)/mm(3)]. The earlier the specimens
      were taken after onset, the lower the expressed levels were. (2) There was a
      positive correlation of the expressions of CD19 and CD19(+)/CD23(+) between acute
      and convalescent stage (P < 0.01);there was also a positive correlation between
      the expressions of CD19 and CD19(+)/CD23(+) during acute and convalescent stage
      (P < 0.01). (3) A negative correlation was found between the duration of fever
      and the level of CD19 and CD19(+)/CD23(+) in acute stage (P < 0.01). CONCLUSION:
      The results indicate that B cells and CD23(+) B cells were significantly
      inhibited during the onset of IM in the patients, that with the recovery of the
      disease, the condition was gradually improved, and that the more evidently the
      CD19 and CD19(+)/CD23(+) decreased, the more serious the clinical symptoms were
      and the longer time the recovery needed. The levels of CD19 and CD19(+)/CD23(+)
      expressions may be useful in diagnosis and predicting the severity.

PMID- 15482677
TI  - [Neuropsychological characteristics of selective attention in children with
      nonverbal learning disabilities].
AB  - OBJECTIVE: To investigate the neuropsychological characteristics of selective
      attention such as attention control, working memory and attention persistence of
      frontal lobe in children with nonverbal learning disabilities (NLD). METHODS:
      With Auditory Detection Test (ADT), Wisconsin Card Sorting Test (WCST) and C
      WISC, 14 children with NLD and 23 controls were tested and the results of sub
      tests of C-WISC were analyzed with factor analysis. ADT was mainly applied to
      test the ability of auditory discernment and the function of dominance
      lateralization in the cerebra; WCST was employed to test the function of working
      memory which was based on the frontal lobe, and, C-WISC, to test the intelligent
      structure and characteristics. RESULTS: Compared with control group, the correct
      response rate of ADT in NLD group was much lower (P < 0.01), and the number of
      incorrect response was much larger (P < 0.01). Children with NLD had deficits of
      auditory selective attention. Moreover, the number of categories achieved (CA)
      and perseverative error (PE) of WCST were much lower (P < 0.05), which indicated
      that children with NLD had the disorders of selective attention and performance
      function. Factor analysis showed that perceptual organization (PO) related to
      visual space and freedom from distractibility (FD) related to attention
      persistence in NLD group were obviously lower than those in control group (P <
      0.01, P < 0.05). These findings further supported the above-mentioned results.
      CONCLUSIONS: Children with NLD had attention control disorder and working memory
      disorder mainly in frontal lobe; we suppose that the disorder in right frontal
      lobe was distinctive.

PMID- 15482678
TI  - [Influence of intestinal dysbacteriosis on immune and hematopoietec function in
      mice].
AB  - OBJECTIVE: To study the effects of intestinal microflora alteration on specific
      and nonspecific immune function and hematopoietic function of mice. METHODS:
      Sixty BALB/C mice were divided at random into two groups, experimental group and
      control group, with 30 mice in each. The mice in the experimental group were
      given kanamycin 50 mg while those in the control group were given distilled water
      intragastrically everyday for consecutive 10 days. After the 10 day treatment all
      the mice were sacrificed, and the cecal contents were collected for quantitative
      analysis of the intestinal bacterial flora. Certain indexes of immune function,
      including phagocytosis rate of macrophages, number of T lymphocytes positively
      stained by esterase and serum interleukin 2 (IL-2) content, and the weight of the
      spleen, granulocyte-macrophage colony stimulating factor etc. as indexes of
      hematopoietic function were determined. RESULTS: In the group, the quantity of
      Enterobacteriaceae, Enterococcus, Bifidobacterium and Lactobacillus were
      significantly lower than that in the control group (P < 0.01). The number of PFC
      (plaque forming cells), the phagocytosis rate of macrophage, the number of T
      lymphocytes with positive NANE staining, the level of IL-2 significantly
      decreased when compared with that in the control group (P < 0.01). The weight of
      the spleen in the experimental group decreased when compared with that in the
      control group (P < 0.01). Levels of IL-3, GM-CSF, the total number of WBC and the
      proportion of neutrophil remarkably decreased as compared to that in the control
      group (P < 0.01). Analysis of the correlations between normal microflora,
      immunologic and hematopoietic indexes showed that marked positive correlations
      between the quantity of Bifidobacteria and each immune index including the levels
      of IL-3 and GM-CSF. There was a positive correlation between IL-2 and IL-3, IL-2
      and GM-CSF as well. CONCLUSION: The application of antibiotics may cause changes
      in the structure and quantity of intestinal microflora. The dysbacteriosis may
      decrease the immune function of organism. The dysbacteriosis may decrease the
      hemopoietic function. The dysbacteriosis, the decrease in immune and
      hematopoietic function may affect one another. The balance in microecosystem
      should be emphasized and antibiotics should be applied rationally to reduce the
      side effects such as dysbacteriosis.

PMID- 15482679
TI  - [Two questions about "Understanding the hemorrhage due to late onset vitamin K
      deficiency"].

PMID- 15482680
TI  - [Assessment of sleep disorders in children with Tourette's syndrome].

PMID- 15482681
TI  - [Treatment of 64 cases with compound diphenoxylate poisoning with naloxone].

PMID- 15482682
TI  - [A case of allergic purpura with initial symptom of hypertensive encephalopathy].

PMID- 15482683
TI  - [Bilateral renal enlargement as the first symptom in a child with acute
      lymphoblastic leukemia].

PMID- 15482684
TI  - [Current epidemiology of viral hepatitis: who is affected and who can be
      protected?].

PMID- 15482685
TI  - [Seroepidemiologic study of hepatitis A in the community of Madrid during the
      year 2002].
AB  - INTRODUCTION: The aim of this study was to investigate the prevalence and risk
      factors associated with hepatitis A virus (HAV) infection in a representative
      population sample to determine who can benefit from vaccination strategies and to
      investigate the age limit at which previous HAV antibody screening is not
      required. METHODS: From April to September 2002, we studied a total of 557
      patients, 90 children and 467 blood donors, aged 1-65 years. Information on
      demographic variables (age, gender, place of residence and education level) was
      recorded. Patients with history of hepatitis or other liver diseases were
      excluded. Anti-HAV antibodies (IgG) were determined with an automated enzyme
      immunoassay (AxSYM, Abbott Diagnostics). The chi-square and Mantel-Haenszel tests
      were used for the statistical analysis. RESULTS: The overall prevalence of HAV
      infection was 41.5%. There was a significant increase in prevalence with age (chi
      square TL:205, P < .0001), with rates from the youngest to oldest groups of 5.5%,
      23.5%, 28.1%, 64.2% and 93.2%, respectively. Apart from age, the only other risk
      factor independently associated with prevalence was the level of education, with
      higher prevalence at the lower education levels (OR 5 2.7; chi-square = 32.11, P
      < .0001). CONCLUSIONS: The prevalence of anti-HAV antibodies has decreased in
      recent years in the community of Madrid. Among the population less than 35 years
      of age, 75% of individuals are susceptible to the infection and could benefit
      from universal vaccination without previous screening for anti-HAV antibodies.

PMID- 15482686
TI  - Hepatitis B virus genotypes identified by a Line Probe Assay (LiPA) among chronic
      carriers from Spain.
AB  - Genotypes A and D of the hepatitis B virus were found to be prevalent among 278
      chronic carriers residing in Spain, and genotypes B, C, E and F were detected
      with significant frequency (9%). Two genotype E infections corresponded to
      carriers born in Spain who had never traveled to Africa. These results indicate
      that genotype E is beginning to circulate in the Spanish population in the same
      way that genotype F did in the past.

PMID- 15482687
TI  - [Clinical study and analysis of risk factors for mortality in 86 cases of
      infectious endocarditis in children and adolescents in Argentina: 1988-2000].
AB  - INTRODUCTION: IE is a rare infection in children. Scarce reports with large
      number of patients are published. METHODS: Between January 1988 to December 2000
      we analyzed all cases of IE cases admitted to our hospital. RESULTS: 86 cases of
      IE (4.9/10,000 admissions) in 86 children were diagnosed. The median age was 7.6
      years. In 77% of patient previous cardiac disease was detected, interventricular
      defects and Tetralogy of Fallot were the more frequent. Three percent of children
      had rheumatic heart disease. Thirty-six percent of children had previous heart
      surgery. Fifty-seven percent have been received previous antibiotics. Eighty
      seven percent had positive blood cultures, being the S. aureus and S. viridans
      the predominantly. Forty-eight percent of children had complications. The
      metabolic disorders and the nosocomial infections were the most frequent. Twenty
      four percent required surgery, 24% of them in the first week of the diagnosis.
      The mortality in operated children was 19%. In the multivariate analysis we could
      observe that children with more than 7 years and S. aureus isolation in blood
      cultures had more incidence of complications and posterior surgery (p < 0.05).
      Children with S. aureus IE had longer duration of fever, more incidence of
      complications than patients with S. viridans IE (p < 0.05). Ten percent of
      children were treated as outpatients. The global mortality was 12,8%. Previous
      surgery (OR = 6.89; IC 95% 1.54-30.7) and previous antibiotic treatment (OR =
      9.98; IC 95% 1.12-88.8) were the factors related with higher mortality in the
      multivariate analysis. S. aureus was the predominat pathogen and caused more
      morbidity and mortality than S. viridans IE. CONCLUSION: Children with IE with
      previous surgery and previous antibiotic treatment died with more frequency.

PMID- 15482689
TI  - [Extrahepatic manifestations of hepatitis C virus infection].
AB  - Hepatitis C virus predominantly affects the liver, although it may also produce a
      number of extrahepatic manifestations, such as mixed cryoglobulinemia, salivary
      and lacrimal gland dysfunction, and several types of kidney disease. The
      pathogenesis of these conditions is not completely understood, but immunologic
      mechanisms are involved in many cases. In some patients with hepatitis C virus
      infection, the extrahepatic manifestations predominate and their proper diagnosis
      and management is very important.

PMID- 15482688
TI  - [Clinical and microbiological characteristics of neutropenic enterocolitis in
      adults with blood cancer in the National Cancer Institute of Bogota D.C.
      (Colombia)].
AB  - OBJECTIVES: This study describes the clinical, epidemiological and
      microbiological characteristics of adult patients with blood cancer and
      neutropenic enterocolitis treated in the Instituto Nacional de Cancerologia
      (National Cancer Institute) in Bogota, Colombia. METHODS: The clinical histories
      of 692 adult patients hospitalized in the Instituto Nacional de Cancerologia
      between 1997 and 2001 with a diagnosis of leukemia or lymphoma were reviewed.
      Thirty-five of these cases met the criteria for probable or confirmed neutropenic
      enterocolitis. RESULTS: Twenty-two cases were confirmed and the remaining 13 were
      probable neutropenic enterocolitis. All patients were undergoing chemotherapy and
      all presented watery diarrhea and abdominal pain. In addition, 17% had melena and
      25% severe vomiting. Eight of 26 stool cultures (30%) and 17 of 32 (58%) blood
      cultures were positive for potentially pathogenic microorganisms, particularly
      gram-negative bacilli. Three patients with probable neutropenic enterocolitis and
      ten confirmed cases died (37%); mortality was higher among patients who were
      managed surgically. CONCLUSION: Neutropenic colitis presents as a multifactorial
      syndrome in patients with blood cancer undergoing cytotoxic therapy with agents
      such as cytosine arabinoside, etoposide, vincristine, cyclophosphamide and
      corticoids. This highly lethal complication is partly due to infections caused by
      gram-negative bacilli.

PMID- 15482690
TI  - [Recommendations for the treatment of severe in-hospital pneumonia. Spanish
      Society of Critical, Coronary, and Intensive Medicine. Spanish Society for
      Respiratory Tract Pathology. Spanish Society of Infectious Diseases and Clinical
      Microbiology].
AB  - INTRODUCTION: Given the sanitary repercussion of serious intrahospital pneumonia
      (SIP), representatives of three scientific societies (SEMICYUC; SEPAR and SEIMC)
      have developed during 2002 and 2003 a practical guide for its treatment. METHOD:
      A task force was constituted to value five clinical situations related with the
      treatment of SIP: 1) critical revision of the existent guidelines and groups of
      risk definition; 2) entry criteria in ICU for SIP; 3) SIP treatment in function
      of the groups of risk; 4) special situations in SIP treatment, and 5) control
      treatment. After the bibliographical revision drafts were developed and discussed
      until the elaboration of the final document. RESULTS: It is necessary the
      stratification of the patients according to the presence or not of risk factors
      in order to make an appropriate use of treatments. SIP without risk factors can
      be treated with monotherapy with several antibiotics. SIP with risk factors
      specifies therapy combined with betalactamic plus aminoglycoside. Its
      substitution for a quinolon is a topic debate. Infections for multiresistance
      microorganisms require an individualized approach that can end up including the
      use of topical antibiotics. In SIP without microorganism isolation the use of a
      score system can be of utility in the taking of decisions. Revision of the
      therapeutic rule after 72 hours, carrying out the necessary adjustments according
      to the clinical evolution and microbiological results is necessary in all cases.
      CONCLUSIONS: Scientific evidence in the treatment of SIP allows the development
      of different strategies to achieve a higher efficiency both in antibiotic
      handling and in the control of its evolution.

PMID- 15482692
TI  - [Necrotic lesion in a patient with hepatitis C virus liver disease under
      treatment with pegylated interferon].

PMID- 15482691
TI  - [Advances in the immunopathology of HIV infection].
AB  - The progressive and irreversible destruction of the immune system represents the
      hallmark of HIV infection. Even though this process is directly related to the
      infection of CD4 lymphocytes, the destruction of this lymphocyte population
      observed along infection is not solely due to a direct cytopathic effect elicited
      by HIV replication. AIDS immune pathogenesis is an extremely complex phenomenon
      involving different mechanisms which are not fully understood yet. In this
      article the mechanisms involved in HIV infection and destruction of target cells
      and the immune response elicited by HIV are analysed. Finally, viral escape
      mechanisms to host immune response are considered.

PMID- 15482693
TI  - [A girl with fever, swelling and unilateral velopalatine procidentia].

PMID- 15482695
TI  - [Delay in the diagnosis and treatment of hospitalized patients with
      tuberculosis].

PMID- 15482696
TI  - [Bordetella bronchiseptica pneumonia in patients with HIV].

PMID- 15482697
TI  - [Pyomyositis associated with HIV-1 infection].

PMID- 15482698
TI  - [Biomarkers of vascular inflammation and subclinical atherosclerosis in the
      metabolic syndrome].
AB  - BACKGROUND AND OBJECTIVE: The metabolic syndrome (MS) is linked to an increase of
      cardiovascular mortality and morbidity, the pathological substrate of
      cardiovascular events being atherosclerosis. Inflammatory phenomena play a role
      in the genesis of atherosclerosis. The aim of this study was to analyze the
      vascular (adhesins) and systemic [interleukins, amyloid A serum protein (AAS), C
      reactive protein (PCR)] inflammation markers as well as hemodynamic parameters
      and the presence or absence of subclinical atherosclerosis measured by intima
      media thickness (TIM) determination in MS. PATIENTS AND METHOD: In this
      transversal study we enrolled 29 patients (18 men,11 women) with a diagnosis of
      MS. We assessed interleukins (IL-1beta, IL-6, TNF-alpha, TGF-beta, MCP-1),
      intercellular and intervascular adhesions molecules (sICAM-1, sVCAM-1), systemic
      inflammation markers (PCR, AAS), microalbuminuria and, as a lipidic oxidation
      marker, urinary F2 isoprostanes (F2I). TIM was measured by ultrasounds. Ten
      healthy people with a similar age were included as a control group. RESULTS:
      Patients with MS, when compared with the control group, showed higher levels of
      homocysteine (10 [0.5] vs 7.9 [0.5] micromol/l; p < 0.05), sICAM1 (263 [13] vs
      203 [14] ng/ml; p < 0.01), IL-6 (7.1 [0.5] vs 4.6 [0.6] pg/ml; p < 0.05), TGF
      beta (34 [1.7] vs 26 [1.4] ng/ml; p < 0.01), PCR (0.69 [0.07] vs 0.23 [0.03]
      mg/dl; p < 0.001), AAS (9.7 [0.7] vs 6.7 [0.7] microg/ml; p < 0.01),
      microalbuminuria (32 [13] vs 3.2 [0.14] mg/g creatinine; p < 0.05), and F2I (22.4
      [2.5] vs 9.1 [0.69] pg/mg creatinine; p < 0.001). TIM in the MS group was greater
      than in the control group (1.14 [0.14] vs 0.79 [0.02] mm; p < 0.05). F2I values
      were directly correlated with TIM, systolic arterial pressure and pulse pressure.
      CONCLUSIONS: Our results show that in MS there is an increase of vascular
      inflammation and lipooxidation markers and a higher prevalence of subclinical
      atherosclerosis.

PMID- 15482699
TI  - [Long term impact of treatment in alcoholics. Results from a 10-year longitudinal
      follow-up study of 850 patients].
AB  - BACKGROUND AND OBJECTIVE: Alcohol dependence syndrome is defined as a chronic
      disease. Nevertheless, few prospective studies have been conducted in order to
      assess the long term impact of treatment in the course of the disease. Moreover,
      those studies have not included drinkers from wine drinking cultures. This study
      was designed to assess prospectively the long term course of alcoholism and the
      impact of treatment on it, in a sample of Spanish drinkers. PATIENTS AND METHOD:
      850 alcoholics aged 16 to 55 years who entered treatment during 1988-1989 in 8
      specialized centres of the Catalan Drug Addiction Network were included in the
      study (75.6% of eligible patients). Patients had to meet DSM III criteria for
      alcohol dependence, a stable home address and a close relative willing to provide
      collateral information. Evaluation was carried out at 0, 1, 5 and 10 years. 15
      and 20 years assessments are also planned. RESULTS: At 10 years of follow up, 131
      (15.4%; 95% confidence interval [CI], 13-18) patients had died, 656 (77.2%; 95%
      CI, 75-80) were alive and 63 (7.4%; 95% CI, 5-9) could not be located. 54
      patients (6.4%; 95% CI, 5-8) refused to be interviewed. Drinking patterns for the
      last 3 years was evaluated in 588 (70%; 95% CI, 67-73) patients: 311 (37%; 95%
      CI, 34-40) were abstinent, 58 (7%; 95% CI, 5-9) were controlled drinkers and 219
      (26%; 95% CI, 23-29) were heavy drinkers. Abstinent patients had lower morbidity
      and casualties as well as a less tendency to use emergency room services. Also,
      abstinence was significantly related to lower levels of psychosocial stress and
      better global functioning, especially in the sociolaboral area. CONCLUSIONS: Our
      results challenge the popular belief that alcoholics are chronic relapsers. The
      changes induced by treatment appear to be long lasting, with better outcomes in
      the group of abstinent patients. Even though treatment is effective for a high
      percentage of patients, mortality rates are 4 and 6 times higher than expected
      for men and women respectively.

PMID- 15482700
TI  - [Prognostic factors for mortality related to nutritional status in the
      hospitalized elderly].
AB  - BACKGROUND AND OBJECTIVE: The proportion of elderly patients hospitalized in
      acute care wards has progressively increased. Patients with a decreased
      functional status are prone to have malnutrition which negatively affects their
      prognosis and increases mortality. However, it is unclear whether functional and
      nutritional status are independent risk factors of mortality. PATIENTS AND
      METHOD: We investigated the relation between functional status (Katz index) and
      nutritional parameters and the incidence of mortality in a prospective,
      observational study of a cohort of elderly patients who were admitted to an
      internal medicine ward. Prevalence of malnutrition upon admission and cumulative
      incidence rate of in-hospital mortality were computed. Also, potential
      nutritional and functional prognostic factors for in-hospital mortality were
      identified by multiple logistic regression. RESULTS: The prevalence of
      malnutrition in 105 patients included in the cohort was 57.1% (95 percent
      confidence interval, 47.1% to 66.8%). The incidence of in-hospital mortality was
      14.3% (95 percent confidence interval, 8.2% to 22.5%). After adjustment,
      independent prognostic factors for in-hospital mortality were: a high level of
      functional dependence (F and G categories of Katz index, OR 6.1; 95 percent
      confidence interval, 1.4 to 26.3), diminished levels of serum transferrin (each
      decrement of 1g/L, OR 8.3; 95 percent confidence interval, 3.4 to 20.0) and
      lymphocyte cell counts (each decrement of 0.5 x 10(9) cells/L, OR 2.3; 95 percent
      confidence interval, 1.5 to 3.5). CONCLUSIONS: The prevalence of malnutrition and
      the incidence of mortality are very high in the hospitalized elderly. In our
      cohort, decreased serum transferrin and lymphocyte cell count, and an increased
      level of functional status were associated with an increased risk of in-hospital
      mortality. Given the high prevalence of geriatric patients in acute care
      hospitals, strategies to promote an adequate nutrition may reduce the risk of
      death.

PMID- 15482701
TI  - [Evaluation of the diagnostic efficacy of patients with dyspepsia in the
      consulting between internists and general practitioners].
AB  - BACKGROUND AND OBJECTIVE: Our goal was to evaluate the efficacy of internal
      medicine consulting (CIM) in primary care (PC) for the care of patients with
      dyspepsia. PATIENTS AND METHOD: Prospective case-control study of a population of
      87,016 inhabitants during a 2 years period. We included patients with dyspepsia
      (319) jointly attended by a family physician (FP) and consulting internists (CI).
      The CI went weekly to the primary care center (PCC) to attend patients who would
      have been referred to the hospital outpatient clinic for specialized care (SC).
      As control group, 775 patients with dyspepsia were randomly and simultaneously
      chosen among a total of 29,317 first medical referrals during the period of the
      study. RESULTS: 5.36% of the consultations for SC were patients with dyspepsia
      (annual incidence of 183 patients/1,000 inhabitants). We observed a significant
      reduction in: mean time for SC (26.4 days; 22.4-30.4), mean number of tests per
      patient ordered by SC (0.77; 0.42-1.12), mean time for patient information on the
      tests ordered by SC (27.3 days; 18.7-35,9), mean time for the resolution of the
      process (27.3 days; 18.4-36.2) and rate of specialized follow-up visits (25.2%;
      18.5-31.9); p < 0.005 in all cases. The resolution rate of the process (37.2%;
      25.7-48.7) and the discharge rate (38.7%; 28.9-48.5) were significantly higher
      for CIM (p < 0.01 in both cases). The referral rate for SC showed a negative
      correlation (r = -0.97; p < 0.01) with the quality of the management; this rate
      related to the type of training, age and years of medical practice of the GPs.
      Satisfaction of patients with the CIM was very high. CONCLUSIONS: The CIM with PC
      improves the efficacy of the specialized medical care of patients with dyspepsia.

PMID- 15482702
TI  - [Inflammation and metabolic syndrome].

PMID- 15482703
TI  - [Long term evolution of chronic alcoholism: keys for reflection].

PMID- 15482704
TI  - [Ethical and legal considerations on the use of animals with experimental
      purpose].

PMID- 15482705
TI  - [Chronic constipation].

PMID- 15482706
TI  - [Imported malaria: difficulties in the diagnosis and treatment].

PMID- 15482707
TI  - [Seroprevalence of Borrelia burgdorferi infection in the area of Valles
      Occidental (Barcelona, Spain)].

PMID- 15482708
TI  - [Angiogenesis and colorectal cancer: a predictive and prognostic role for the
      vascular endothelial growth factor].

PMID- 15482709
TI  - [The Catholics and organ donations].

PMID- 15482710
TI  - [Dysphagia and constipation as clinical manifestations of anti-Hu paraneoplastic
      syndrome].

PMID- 15482711
TI  - [Epilepticus status and valaciclovir in chronic renal failure].

PMID- 15482712
TI  - [Economic cost of peripheral blood progenitor cell transplantation in Spain].
AB  - BACKGROUND AND OBJECTIVE: Peripheral blood hematopoietic progenitor cell
      transplantation (PCT), both autologous and allogeneic, has been consolidated in
      the last decades as an important tool in the treatment of a number of
      oncohematologic malignancies. Nevertheless, there are scarce data about the real
      cost of the autologous procedure in our setting, and to date the economic impact
      of allogeneic PCT in our health system is unknown. PATIENTS AND METHOD: In the
      present study a comparative analysis of the economic cost of both methods of PCT
      was carried out in a series of 67 consecutive patients who were eligible for
      autologous PCT (n = 48), or allogeneic PCT (n = 19) in a 2 year study period. The
      expenses derived from pretransplant studies, from the collection and processing
      of hematopoietic progenitors, and from the transplantation procedure itself were
      evaluated. RESULTS: The collection of hematopoietic progenitors was significantly
      more expensive in autologous than in allogeneic PCT (p = 0.0001), owing both to
      the difficulty in the mobilization of such cells in patients who have been
      treated for the underlying disease and to the higher costs derived from the
      criopreservation of the collected material. Nevertheless, the costs of the
      pretransplant studies were significantly higher in allogeneic PCT due to the
      expenses of histocompatibility studies (p = 0.0001). Similarly, the costs derived
      from the transplantation procedure itself were significantly higher in allogeneic
      procedures (p = 0.0002) as those patients required a longer hospitalization, and
      also because of the higher number of patients requiring conditioning regimens
      including total body irradiation. CONCLUSIONS: From these data we conclude that
      the real cost of PCT in our setting is 24,000 Euros for the autologous procedure,
      while it is 34,000 Euros in the context of allogeneic transplantation.

PMID- 15482713
TI  - [Validation of the Spanish version of the Palliative Care Outcome Scale].
AB  - BACKGROUND AND OBJECTIVE: The objective of this study was to translate the
      Palliative Care Outcome Scale (POS) into Spanish and to validate it. MATERIAL AND
      METHOD: The translation and adaptation was based on the conceptual equivalence of
      the terms used. In order to study the psychometric properties, 200 patients
      receiving palliative care were asked to fill out the POS questionnaire, the
      European Organization for Research on Cancer Treatment Quality of Life
      Questionnaire (EORCT QLQ C-30), the Barthel Index and the Karnofsky Index on
      their first visit. The Spanish version of the POS questionnaire was given to the
      patients again, a week later, to measure the intra-observer reliability. RESULTS:
      There were no major problems with the translation and adaptation process. The
      Spanish POS adapted very well for both the staff and the patients versions. Inter
      and intra-observer reliability was good, with intraclass correlation
      coefficients of between 0.61 and 0.93 according to the item. Internal consistency
      analysis showed a Cronbach's alpha of 0.62 for the staff version and 0.64 for the
      patients version. Most of the Spanish POS correlated with the EORTC QLQ C-30
      emotional function scale and quality of life scale. CONCLUSIONS: The Spanish POS
      is a valid and reliable instrument for measuring the quality of life of patients
      receiving palliative care. It is useful in research as well as in everyday
      clinical practice.

PMID- 15482714
TI  - [Preoperative erythropoietin as blood conservation technique for elderly patients
      in elective orthopedic surgery].
AB  - BACKGROUND AND OBJECTIVE: Preoperative anemia is a major risk factor for
      perioperative transfusion in orthopedic surgery and aging is associated with an
      increased risk for developing anemia. The aim of this study was to compare the
      efficacy and safety of preoperative epoetin alfa in patients older and younger
      than 65 years in orthopedic surgery. PATIENTS AHD METHOD: This study involved 75
      patients scheduled for total joint arthroplasty who had an hemoglobin level
      between 100 and 130 g/l. Patients were assigned to receive weekly doses of
      subcutaneous epoetin alfa (40000 IU) on days -21, -14, -7, -1 before surgery. We
      tabulated age, weight, gender, baseline analytic parameters, perioperative
      evolution of the mean hemoglobin level, transfusion, side effects and
      complications. RESULTS: Fifty-four patients were included in group A (> or = 65
      years) and 21 in group B (< 65 years). The two study groups did not differ in
      terms of demographic characteristics and baseline analysis but differed in age
      and associated diseases. The preoperative increase in mean hemoglobin level (20
      and 18 g/l) and transfusion rate (15% and 14.3%) were similar in both groups.
      There were no complications associated with the use of epoetin alfa. CONCLUSIONS:
      Preoperative epoetin alfa administration seems to be as effective and safe in
      patients younger as in those older than 65 years.

PMID- 15482715
TI  - [Venous thromboembolism in patients with neurosurgical process or stroke. A
      prospective analysis from the RIETE registry].
AB  - BACKGROUND AND OBJECTIVE: We studied the characteristics of thromboembolic
      disease in patients who have suffered a deep venous thrombosis or a pulmonary
      thromboembolism with the occurrence, two months before, of a neurosurgical
      process or a stroke. PATIENTS AND METHOD: We analyzed the variables of 57
      patients who underwent a neurosurgical operation and those of 86 patients who
      suffered a stroke. These variables were included in the Computerised Records of
      Thromboembolic Disease. RESULTS: The average age was of 62.3 (1.9) for
      neurosurgical and 71.7 (1.5) for stroke patients (p < 0.001). Prophylaxis was
      previously applied to 31.6% of neurosurgical patients and to 37.2% of patients in
      the stroke group. Most patients were treated with low molecular weight heparin
      during the acute phase of the illness. In both groups, 50% of deaths was
      associated with thromboembolic disease. The proportion of deceases was related to
      the associated disease and it was significantly higher in the stroke group (18%
      versus 4.2% in the neurosurgical group, p = 0.028). CONCLUSIONS: In our study,
      thromboembolic disease was responsible of 50% of deaths. Stroke patients make up
      a group with a bad prognosis due to their older age and higher frequency of
      associated pathology; they have a higher risk of death.

PMID- 15482716
TI  - [Outcome evaluation in palliative care].

PMID- 15482717
TI  - [Should erythropoietin be administered to old patients in the preoperative period
      of orthopaedics surgery?].

PMID- 15482718
TI  - [End-of-life sedation].

PMID- 15482719
TI  - [Diagnostic evaluation of pleural effusion].

PMID- 15482720
TI  - [Do non-steroidal anti-inflammatory drugs modify the antiplatelet effects of
      aspirin?].

PMID- 15482721
TI  - [Elevation of troponine I in acute pericarditis: a case report].

PMID- 15482722
TI  - [Bacteremia due to Enterococcus gallinarum in a patient with varicella and late
      sarcoidosis].

PMID- 15482723
TI  - [Secondary hypertension due to Cushing syndrome caused by macronodular adrenal
      hyperplasia, refractory to medical therapy].

PMID- 15482724
TI  - [Radiation leukoencephalopathy. Clinical and radiological evolution].

PMID- 15482725
TI  - [Visceral leishmaniasis and consumption coagulopathy: a case report and review of
      the literature].

PMID- 15482726
TI  - [Web pages citation as bibliographical references].

PMID- 15482727
TI  - [Hepatopulmonary syndrome and HIV infection].

PMID- 15482728
TI  - [Predictive model for community acquired bacteremia in patients from an Internal
      Medicine Unit].
AB  - BACKGROUND AND OBJECTIVE: Clinical suspicion of bacteremia lacks of sensitivity,
      specificity or predictive values enough to be clinically useful. The aim of this
      study was to develop a clinical prediction rule of bacteremia for patients
      hospitalized in an internal medicine department, with community-acquired
      symptoms, who had blood cultures obtained. PATIENTS AND METHOD: A prospective
      study, including all patients who had blood cultures in the first 48 h after
      admission, was performed. A clinical prediction rule of bacteremia was derived
      from a random sample of two thirds of the patients (derivation cohort) and
      validated in the remaining (validation cohort). After bivariate analysis,
      significant variables were included in a stepwise logistic regression analysis.
      In every patient out of the derivation and validation cohorts a score, derived
      from the addition of points for each of the significant predictor variables of
      logistic regression, was obtained; according to this score, 4 groups were formed,
      and the prevalence of bacteremia in each of them was calculated. Calibration and
      discrimination were evaluated by the Hosmer-Lemeshow test and area under the ROC
      curve respectively. RESULTS: Four hundred and forty-eight blood cultures were
      obtained; the prevalence of bacteremia was 25.2%. Independent predictors of
      bacteremia in the bivariate analysis were urinary focus of infection, body
      temperature >= 38.3 degrees C, presence of band forms, ESR >= 70 mm, platelets <
      200 * 103/microl, blood glucose >= 140 mg/dl, urea >= 50 mg/dl, C-reactive
      protein >= 12 mg/dl, and albumin < 3 g/dl. According to the score, in the
      derivation cohort, four groups with increasing prevalence of bacteremia were
      identified; in the group with a score between 0 and 3, the prevalence was 2.4%;
      between 4 and 5: 15.7%; between 6 and 7: 42.9%; and score >= 8: 65%. In the
      validation cohort, the prevalence was 4.1%, 22.6%, 29.3%, and 80%, respectively.
      The model showed good calibration (Hosmer-Lemeshow *2 = 4.91; p = 0.77). Area
      under the ROC curve was 0.81 (95% confidence interval, 0.76-0.86) in the
      derivation cohort, and 0.77 (95% confidence interval, 0.69-0.85) in validation
      cohort. CONCLUSIONS: Our model, constructed with 9 variables and a simple
      additive point system, had good calibration and discrimination, which points at
      its usefulness to estimate the probability of bacteremia in patients admitted in
      an Internal Medicine department. Used in conjunction with clinical judgement, the
      model can be useful in the decision-making process, concerning blood cultures
      obtention, clinical monitoring, and empirical antimicrobial therapy. Before
      application, additional prospective validation in other settings is warranted.

PMID- 15482729
TI  - [Quick and early diagnostic outpatient unit: an effective and efficient
      assistential model. Five years experience].
AB  - BACKGROUND AND OBJECTIVE: To analyze the applicability of an out-patient Quick
      and Early Diagnostic Unit (QEDU) to evaluate patients with a potential life
      threatening disorder on an out-patient basis. PATIENTS AND METHOD: We analyzed
      prospectively all patients attended in the unit for five years (1997-2001). We
      compared patients with lung cancer and colorectal cancer admitted to hospital for
      conventional study versus patients studied at the unit. RESULTS: We attended
      2,748 patients in total Main reasons for consultation were abdominal pain,
      asthenia-anorexia, neurologic symptoms, anemia and palpable tumors. The most
      frequent diagnostic category corresponded to gastroenterological diseases and
      neoplastic diseases. The mean interval (standard error) for the first visit was
      4.9 (3.4) days and for diagnosis it was 5.7 (6.5) days. Some 95% patients
      displayed a high degree of satisfaction by the questionnaire. In patients with
      cancer of the colon studied at the QEDU, we observed a reduction in the average
      interval for diagnosis which was highly significant (p = 0.03). The overall costs
      of final diagnosis were also lower for the QEDU model. CONCLUSIONS: The QEDU unit
      represents an alternative to in hospital admission for diagnostic workouts, which
      is fully feasible in our setting. It can result in the same efficacy and a higher
      efficiency than hospital admission.

PMID- 15482730
TI  - [ACT/AA polymorphism could duplicate the APOE*epsilon4-associated Alzheimer's
      disease risk].
AB  - BACKGROUND AND OBJECTIVE: The association between the presence of the allele
      APOE*epsilon4 (apolipoprotein E) and sporadic Alzheimer disease (AD) has been
      long established. However, the possible influence of other genetic factors is
      still under debate. This study investigated the role of the a 1-antichymotrypsin
      (ACT) gene as a susceptibility factor for developing late-onset AD in the
      population of Navarra. PATIENTS AND METHODS: The study group included 98 patients
      with late-onset AD and 188 control individuals 70-71 years of age.
      APOE*epsilon2,*epsilon3,*epsilon4 and ACT codon -17*A,*T polymorphisms were
      analyzed by PCR-RFLP. Statistical analyses were performed determining the chi
      square test, using 2 x 2 contingency tables and logistic regression to calculate
      odds ratios. RESULTS: APOE*epsilon4 allele frequency was significantly higher in
      AD patients than in controls (odds ratio [OR] = 3.02; 95% confidence interval
      [CI], 1.59-5.73; p < 0.001 in heterozygous carriers, and OR = 9.40; 95% CI, 1.84
      64.43; p = 0.001 in homozygous individuals). We found no significant differences
      in the distribution of ACT polymorphisms between AD cases and controls. However,
      APOE*epsilon4 carriers had a 2.5-fold increased risk of developing AD in the
      presence of the ACT/AA genotype (OR = 10.13; 95% CI, 1.98-97.81; p < 0.001). The
      risk difference, however, did not reach statistical significance (p = 0.271).
      CONCLUSIONS: APOE*epsilon4 heterozygous and homozygous carriers have a 3 and 9
      times higher risk, respectively, of developing AD. We could not demonstrate an
      effect of ACT polymorphisms as a independent risk factor for this disease;
      however, the ACT/AA genotype seems to act as an additional susceptibility factor,
      duplicating the APOE*epsilon4-associated AD risk.

PMID- 15482731
TI  - [Bacteremia: prediction models].

PMID- 15482732
TI  - [Specialized ambulatory care. Present and future].

PMID- 15482733
TI  - [Hemoglobin Korle-Bu [beta73(E17)Asp ->Asn]. First cases described in Spain].
AB  - BACKGROUND AND OBJECTIVE: Hemoblobin Korle-Bu [beta73(E17)Asp->Asn], also known
      as hemoglobin GACCRA, is frequent in African colour population. The interest of
      this work has been confirmed that hemoglobin Korle-Bu is a structural variant
      which mutation is located in the CD73 (GAT->AAT) of the exon 2 of beta gene and
      that this characterises has been made in the first cases found in Spanish
      population. Where to be carrier of African hemoglobins is less frequent. PATIENTS
      AND METHOD: Two unrelated families (4 subjects) from the same geographical area
      were studied because all of them shown an abnormal hemoglobin during a screening
      program of hemoglobinopathies in blood donors. Electrophoretic methods and ion
      exchange HPLC studied this hemoglobin. Globin chains are studied by reverse phase
      HPLC. Automatic sequencing carried out the molecular study. RESULTS: In the
      electrophoretic study and by ion exchange HPLC was observed an abnormal
      hemoglobin. The study of globin chains by reverse phase HPLC revealed the
      presence of three peaks betaX, betaA y alpha. In all the cases, the P50 was
      increased. The molecular study by sequencing revealed the substitution GAT->AAT
      in the codon 73 of beta gene globin. This variant of haemoglobin is named
      hemoglobin Korle-Bu [beta73(E17)Asp->Asn]. CONCLUSIONS: This hemoglobin variant
      becomes important when it is associated with hemoglobin S or C because, although
      it is not associated with a clinical picture severe, when this hemoglobin is
      associated with another kind of alterations of hemoglobin molecule (thalassemias
      or hemoglobinopathies) the clinical could be more severe. So, it is important its
      genetic characterization for the diagnoses of the serious forms.

PMID- 15482734
TI  - [Medical language, ethics and medicine].

PMID- 15482736
TI  - [Sporadic transmission of hepatitis C in dental practice].
AB  - Percutaneous contact with contaminated blood is the principal mode of
      transmission of the hepatitis C virus (HCV). However, the diagnosis of infection
      in patients in whom no parenteral risk factor can be identified allows
      speculation on the existence of other routes of transmission. In the field of
      dentistry, the role of saliva has still not been defined as a potential vehicle
      for infection nor the role of dental treatment as a possible occult factor in the
      sporadic transmission of hepatitis C. HVC-RNA is detectable in the saliva of over
      50% of patients with chronic hepatitis C. The infectivity of the HVC particles
      detected in the saliva has not been determined, though it may be deduced from
      epidemiological studies that their potential for transmission, if it exists, is
      extremely limited. There has been no documented case of HVC transmission in a
      dental clinic. Studies which propose a history of dental treatment as a risk
      factor for HVC infection have not achieved conclusive results. The age
      distribution of the prevalence of HVC could indicate that a risk of iatrogenic
      transmission existed in the past, before the systematic application of universal
      barriers. The transmission of HVC in dental clinics may be considered a very
      infrequent occurrence as long as the norms for the control of cross-infection are
      respected.

PMID- 15482735
TI  - [Burnout and the health of the medical professionals: review and preventive
      options].
AB  - The relevance of stress on health is an increasing interest, as well as the
      growth of job stress in general and specifically of the medical job stress. A
      consequence is the rise of medical burnout. Though burnout rates can change
      depending on organizational contexts and specific samples, all the information
      indicates high rates of prevalence in the medical population. Consequences of the
      syndrome are wide and important, and affect mental health, physical health,
      quality of life and efficiency of physicians. This situation raises the need to
      develop programmes of prevention and intervention that help to control and to
      relieve such effects following the suggestions of the European Union.

PMID- 15482737
TI  - [Tobacco and Parkinson: a pact with the devil?].

PMID- 15482738
TI  - [Gelatinous transformation of bone marrow caused by severe hypothyroidism].

PMID- 15482739
TI  - [Red sea coral sting: a risk associated with tourism].

PMID- 15482741
TI  - [Pneumocephalus in pneumococcal meningitis].

PMID- 15482742
TI  - [Delayed onset progressive cerebral arteriopathy after radiation].

PMID- 15482743
TI  - Assisted reproductive techniques in patients with Klinefelter syndrome: a
      critical review.
AB  - OBJECTIVE: To summarize the existing experience with the use and success rate of
      assisted reproductive techniques (ART), in particular testicular sperm extraction
      (TESE) and intracytoplasmic sperm injection (ICSI), in Klinefelter patients.
      DESIGN: A systematic review of the literature, including all published case
      reports to date. PATIENT(S): Thirty-nine reported successful pregnancies fathered
      by nonmosaic Klinefelter patients. MAIN OUTCOME MEASURE(S): The overall risk of
      transmitting a chromosomal abnormality to the offspring of Klinefelter patients.
      RESULT(S): In nonmosaic and mosaic Klinefelter patients, chromosomally normal
      sperm cells can be extracted from testicular tissue and used for ICSI.
      CONCLUSION(S): The application of ART to Klinefelter patients can be recommended
      as a method to achieve reproduction in this selected infertility patient cohort.

PMID- 15482744
TI  - Infertility practice management. I. Leadership and management style: results from
      the 2002 survey of 374 Society for Assisted Reproductive Technology member
      centers.
AB  - OBJECTIVES: To identify current trends in management and leadership styles in
      Society for Assisted Reproductive Technology (SART) member infertility centers;
      and to understand the similarities and disparities that exist in physicians',
      administrators', and staff perceptions of management and leadership styles in
      these centers. MATERIALS AND METHODS: Questionnaires were developed to collect
      information on the leadership and management styles in place in SART member
      infertility centers. Survey instruments were distributed to the 374 SART centers.
      Survey instruments for one physician, the center administrator, and six staff
      members (two each in nursing, laboratory, and administration) were issued to the
      SART liaison in each of the SART member centers. Respondents included physicians,
      practice administrators, nurses, technicians, patient services, billing, and
      support staff. RESULTS AND DISCUSSION: Analysis of respondents' answers revealed
      that surveyed staff members reported a fairly high degree of job satisfaction.
      Physician and administrator management styles seemed to fall between interactive
      and directive styles; however, physicians and administrators perceived themselves
      as being more interactive than other staff members viewed them. Overall, extreme
      differences were unlikely, given the reported high degree of job satisfaction.
      Finally, survey outcome data were compared with responding centers' ART outcome
      rates as published by the Centers for Disease Control and Prevention (CDC).
      CONCLUSIONS: Overall, although employee job satisfaction seemed to be high, there
      were statistical differences between groups for several questions; the
      disparities in responses for these questions are indicators for potential
      management and leadership consideration. In addition, statistical correlations
      were found between the responses for several questions and the centers'
      respective CDC-published ART outcome rates.

PMID- 15482745
TI  - Impact of detection of bacterial endotoxin in menstrual effluent on the pregnancy
      rate in in vitro fertilization and embryo transfer.
AB  - OBJECTIVE: To examine whether bacterial endotoxin is detectable in menstrual
      effluent and to analyze a possible association between endotoxin levels and a
      pregnancy rate after IVF-ET. DESIGN: Prospective observational study. SETTING:
      University hospital. PATIENT(S): Thirty-eight infertile women undergoing
      endotoxin assay and IVF-ET. INTERVENTION(S): Endotoxin was assayed by the limulus
      amoebocyte lysate test. MAIN OUTCOME MEASURE(S): Levels of bacterial endotoxin
      and a pregnancy rate. RESULT(S): In 38 samples of menstrual effluent taken from
      38 women, bacterial endotoxin was detected with a range of 7.1 to >1,000 pg/mL in
      37 samples and was not detected in 1 sample. After IVF-ET, pregnancy occurred in
      9 of the 38 women. The mean (+/- SD) endotoxin level in these 9 pregnant women
      was 71.3 +/- 52.5 pg/mL and was significantly lower compared with >236.2 +/-
      333.6 pg/mL in the 29 nonpregnant women. All pregnancies occurred in 28 women
      with an endotoxin level of </=200 pg/mL, whereas no pregnancies occurred in 10
      women with an endotoxin level of >200 pg/mL, producing the significantly higher
      pregnancy rate in the former group than in the latter. CONCLUSION(S): Bacterial
      endotoxin was detectable in menstrual effluent from infertile women. The
      pregnancy rate after IVF-ET was significantly higher in women with an endotoxin
      level of </=200 pg/mL than in women with an endotoxin level of >200.0 pg/mL.

PMID- 15482746
TI  - Endometrial endotoxin, assisted reproductive technology, and preterm birth.
AB  - The failure of antibiotic prophylaxis to reduce preterm birth in women at risk
      and the increased rate of preterm birth in singleton pregnancy after ART may have
      a common explanation: persistent bacterial endotoxin in the endometrium, reported
      by Kamiyama et al. as an explanation for reduced fertility.

PMID- 15482747
TI  - So what is the role of menstrual bacterial endotoxin?
AB  - Bacterial infections may adversely affect ART. However, the meaning and risks of
      menstrual endotoxin are not known.

PMID- 15482748
TI  - Microbiology of the endometrium and in vitro fertilization: do we yet understand
      the implications?
AB  - The hypothesis that bacteria in the uterus may be detrimental to an embryo is
      very thought provoking. The data, however, do not yet support that this is a
      clinically relevant issue.

PMID- 15482749
TI  - Can endometrial infection/inflammation explain implantation failure, spontaneous
      abortion, and preterm birth after in vitro fertilization?
AB  - The endometrial cavity is frequently invaded by microorganisms, and subclinical
      endometrial infection or inflammation may play a role in implantation failure
      after IVF, spontaneous abortion, and preterm birth. Microbial products and host
      inflammatory mediators such as cytokines and chemokines can cause trophoblast
      apoptosis and the cascade of events leading to expulsion of the embryo or fetus.

PMID- 15482750
TI  - Bacterial endotoxin in the endometrium and its clinical significance in
      reproduction.
AB  - Bacterial endotoxin was detected in menstrual effluent from infertile women.
      Endometrial endotoxin appears to influence reproductive process because the
      pregnancy rate after IVF-ET was significantly associated with an endotoxin level.

PMID- 15482751
TI  - Fertility treatment when the prognosis is very poor or futile.
AB  - The Ethics Committee makes recommendations about treating or not treating
      patients when clinicians regard the treatment option as futile or having a very
      poor prognosis.

PMID- 15482752
TI  - Prognostic use of mean ovarian volume in in vitro fertilization cycles: a
      prospective assessment.
AB  - OBJECTIVE: To determine the predictive value and to define prognostic threshold
      measurements for mean ovarian volume (MOV) in patients undergoing IVF. DESIGN:
      Prospective cohort analysis. SETTING: Tertiary care center. PATIENT(S): Two
      hundred sixty-seven patients. INTERVENTION(S): Transvaginal ultrasound before
      starting gonadotropins. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved,
      basal hormone levels, and cycle outcomes. RESULT(S): The MOV for the population
      was 4.78 +/- 2.6 cm(3) (range 0.9-21.1 cm(3)). The MOV significantly correlated
      with the majority of prestimulation and poststimulation IVF parameters. Threshold
      analysis demonstrated a lower pregnancy rate associated with a MOV of <2 cm(3)
      (31.6% vs. 55.6%). Threshold analysis revealed a trend toward higher cancellation
      rate associated with a MOV of <2 cm(3) (21.1% vs. 7.3%). CONCLUSION(S): Although
      MOV correlated with IVF stimulation parameters, its use as an adjunct in
      counseling patients during IVF appears to be of limited value. A MOV <2 cm(3) was
      associated clinically with a higher cancellation rate (21.1%) and a lower
      pregnancy rate (31.6%) in those cycles not cancelled. However, these values do
      not deviate far from the mean national IVF outcome rates. There was no absolute
      MOV that was predictive of pregnancy outcome or cycle cancellation.

PMID- 15482753
TI  - Treatment with piroxicam before embryo transfer increases the pregnancy rate
      after in vitro fertilization and embryo transfer.
AB  - OBJECTIVE: To examine the effect of beta-cyclodextrin piroxicam treatment for
      priming of the uterus on the pregnancy outcome of IVF-embryo transfer (ET)
      programs. DESIGN: Prospective, randomized, double-blinded placebo-controlled
      clinical study. SETTING: Large urban medical center. PATIENT(S): One hundred
      eighty-eight consecutive cycles of fresh IVF-ET and 78 cycles of frozen-thawed
      ET. The patients underwent IVF because of tubal, male infertility, unexplained,
      or endometriosis factors. They were randomly divided into treatment and control
      groups. INTERVENTION(S): In the treatment group, 94 cycles in fresh ET and 39
      cycles in frozen-thawed ET the patients received an oral dose of 10 mg of
      piroxicam. In the control group, the same number cycles corresponding to the
      treatment group were treated with placebo. Both groups started piroxicam or
      placebo treatment 1-2 hours before ET. Patients and staff were blinded to the
      treatment. MAIN OUTCOME MEASURE(S): Implantation rate (IR) and pregnancy rate
      (PR). RESULT(S): Piroxicam increased significantly IR (18.7%) and PR (46.8%)
      compared to the control group (8.6% and 27.6%, respectively) in fresh cycles.
      With the exception of an unexplained factor, patients with the tubal, male
      infertility, or endometriosis factor had significantly higher PR in the treatment
      group compared to the control group. The beneficial effect of piroxicam was found
      in patients less than 40 years old, but was not found in patients more than 40
      years. In frozen-thawed cycles, there were statistically significant differences
      between the treatment group and the control group in IR (9.4% vs. 2.3%) and PR
      (25.6% vs. 7.7%), respectively. CONCLUSION(S): Our study showed that piroxicam
      increases IR and PR after IVF-ET in both fresh and frozen-thawed ET cycles. The
      beneficial effect seems to be more remarkable in patients less than 40 years old
      with tubal, male infertility, or endometriosis factors. These results suggest
      that piroxicam treatment before ET is very effective in the priming of a uterus
      suitable for embryo implantation. This is the first study to investigate the
      possible consequence of piroxicam for improving the PR after IVF-ET.

PMID- 15482754
TI  - Postthaw blastomere survival is predictive of the success of frozen-thawed embryo
      transfer cycles.
AB  - OBJECTIVE: To investigate the predictors of postthaw blastomere survival and the
      relationship of blastomere survival to the outcome of frozen-thawed embryo
      transfer (FET) cycles. DESIGN: Retrospective study. SETTING: An IVF unit in a
      tertiary care facility. PATIENT(S): Infertile women undergoing FET cycles with
      embryos cryopreserved on day 3 postinsemination. INTERVENTION(S): FET cycles.
      MAIN OUTCOME MEASURE(S): Embryo survival postthaw, pregnancy (PR), clinical
      pregnancy, and implantation rates. RESULT(S): A significant impact of postthaw
      blastomere survival on the outcome of FET cycles was noted. The thawed embryos in
      the low survival tertile resulted in significantly impaired implantation rate,
      clinical pregnancy rate, and PR compared to embryos in the high survival tertile.
      An inverse association was noted between serum P levels on the day of hCG
      administration and postthaw blastomere survival. CONCLUSION(S): We have
      demonstrated that postthaw blastomere survival is predictive of success of FET
      cycles. The relationship of poor postthaw embryo survival in the setting of
      elevated P is novel and not hitherto described.

PMID- 15482755
TI  - Oocyte quality in patients with severe ovarian hyperstimulation syndrome: a self
      controlled clinical study.
AB  - OBJECTIVE: To investigate the oocyte quality in patients with severe ovarian
      hyperstimulation syndrome (OHSS). DESIGN: Self-controlled clinical study.
      SETTING: University teaching hospital. PATIENT(S): Twenty-two patients from our
      assisted reproductive technology (ART) program who developed severe OHSS during
      their first controlled ovarian hyperstimulation for IVF or intracytoplasmic sperm
      injection (ICSI) (OHSS cycles) during a period of 10 years and had a second ART
      attempt performed in our center in which OHSS did not develop (control cycles).
      INTERVENTION(S): IVF and ICSI. MAIN OUTCOME MEASURE(S): Oocyte yield and quality,
      fertilization rate, embryo yield and quality, implantation rate, and pregnancy
      rate. RESULT(S): The total number of oocytes retrieved and the mean number of
      metaphase II oocytes were significantly higher in patients with OHSS than in
      control cycles. Fertilization rates were similar in both groups of ART cycles,
      and thus the number of viable embryos were significantly higher in OHSS cycles.
      Implantation and pregnancy rates were similar in OHSS and control cycles. Oocyte
      and embryo yield and quality were similar in early and late OHSS. Oocyte yield
      and quality, embryological outcome, and implantation and pregnancy rates were
      similar in patients with and without polycystic ovarian syndrome (PCOS) both in
      cycles developing OHSS and control cycles. CONCLUSION(S): Oocyte quality is not
      compromised in severe OHSS cycles irrespective of whether patients had or did not
      have PCOS.

PMID- 15482756
TI  - Follicle-stimulating hormone and estradiol levels independently predict the
      success of assisted reproductive technology treatment.
AB  - OBJECTIVE: To evaluate the relationship between early follicular phase levels of
      FSH and E(2) and outcomes of therapy with assisted reproductive technologies
      (ART). DESIGN: Retrospective cohort study. SETTING: ART centers in the United
      States. PATIENT(S): Women receiving 19,682 ART procedures performed in 135
      clinics. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates of clinical
      pregnancy, live birth delivery, and high ovarian response (>/=10 oocytes
      retrieved after stimulation). RESULT(S): The ratio of each FSH or E(2) value to
      the respective upper limit of normal value for the clinic was computed. Within
      each age group, rates of pregnancy, live birth, and high ovarian response
      decreased linearly as FSH levels increased. For example, among women 35 years of
      age and younger, pregnancy rates (PR) ranged from 41.1% (FSH ratio 0-0.5) to
      18.5% (FSH ratio >2.0). The three outcomes exhibited a similar downward trend as
      E(2) ratios increased. When both hormone ratios were elevated, outcomes were
      least favorable. These relationships remained statistically significant after we
      adjusted for diagnosis, number of embryos transferred, previous births, previous
      ART therapy, and use of GIFT, zygote intrafallopian transfer (ZIFT),
      intracytoplasmic sperm injection (ICSI), or assisted hatching. CONCLUSION(S): The
      FSH and E(2) ratios predict ART success independent of age and other clinical
      prognostic factors.

PMID- 15482757
TI  - Reducing the dose of human chorionic gonadotropin in high responders does not
      affect the outcomes of in vitro fertilization.
AB  - OBJECTIVE: The lowest effective hCG dose in high responders during IVF-embryo
      transfer (ET) has not been established. This study was performed to confirm that
      a dose of 3,300 IU is sufficient to provide adequate oocyte maturation and
      fertilization. DESIGN: Retrospective review of IVF clinical data. SETTING:
      Infertility center at a tertiary care university. PATIENT(S): Ninety-four IVF
      cycles were analyzed from high responders based on peak E(2) levels. Demographics
      were compared including age, diagnosis, and stimulation protocol.
      INTERVENTION(S): On the day of hCG administration, if E(2) levels were >/=2,500
      but <4,000 pg/mL, patients received 5,000 IU (group A). For levels between 4,000
      pg/mL and 5,500 IU pg/mL, they received 3,300 IU (group B). MAIN OUTCOME
      MEASURE(S): Number of oocytes retrieved, proportion of mature oocytes,
      fertilization rates, chemical and clinical pregnancy rates (PR). The incidence
      and severity of ovarian hyperstimulation syndrome (OHSS) was also analyzed.
      RESULT(S): Mean ages were 35.4 +/- 0.7 and 33.2 +/- 0.7 for groups A and B,
      respectively. Peak E(2) levels differed significantly (2,907 +/- 76 vs. 4,260 +/-
      129 pg/mL), as well as the mean number of eggs retrieved (15.9 +/- 0.9 vs. 20.3
      +/- 1.2). Proportion of mature eggs (81.6% vs. 81.9%), fertilization rate (70.5%
      vs. 68.7%), chemical PR (58.7% vs. 58.7%), and clinical PR (50.0% vs. 43.5%) were
      similar. There was no difference in the incidence of mild, moderate, or severe
      OHSS. CONCLUSION(S): A reduced hCG dose of 3,300 IU results in a similar
      proportion of mature eggs, similar fertilization rates, and similar PRs compared
      to 5,000 IU. Reducing the dose of hCG does not eliminate the risk of OHSS in a
      high-risk group.

PMID- 15482758
TI  - Pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection with
      profound teratospermia.
AB  - OBJECTIVE: To assess the pregnancy outcome of IVF with intracytoplasmic sperm
      injection (ICSI) in couples with profound teratospermia (Kruger's strict criteria
      of zero). DESIGN: Retrospective analysis of 545 consecutive cycles of IVF/ICSI
      performed between January 2000 and January 2003. SETTING: Tertiary care center.
      PATIENT(S): Of 545 IVF/ICSI cycles, 45 patients were identified with a semen
      strict morphology of 0 using Kruger's strict criteria. INTERVENTION(S): Ovarian
      down-regulation (Lupron) was followed by controlled ovarian stimulation
      exclusively with hMG. Embryo transfer was performed 2 days after transvaginal
      aspiration/ICSI. MAIN OUTCOMES MEASURE(S): Pregnancy outcomes and newborn/infant
      status. RESULT(S): Of 45 patients undergoing 54 treatment cycles, 21 patients
      were positive for pregnancy (38.9% pregnancy/cycle). No birth defects were noted
      at time of delivery and all infants had obtained appropriate developmental
      milestones at 1 year of age. CONCLUSION(S): Men with profound teratospermia
      (Kruger's strict criteria of zero) may achieve acceptable pregnancy rates after
      IVF/ICSI thereby alleviating the use of donor sperm in this group. Furthermore,
      no increased risk of birth defects is apparent in this small series.

PMID- 15482759
TI  - Transfer and uterine factors are the major recipient-related determinants of
      success with donor eggs.
AB  - OBJECTIVE: To define the recipient-related determinants of outcome with donor
      eggs. DESIGN: Case-control study. SETTING: Community hospital-based assisted
      reproductive technology (ART) program. PATIENT(S): One hundred thirty-four embryo
      transfers (ETs) in which two recipients were matched to one donor.
      INTERVENTION(S): Controlled ovarian hyperstimulation (COH) and ovum retrieval in
      donors; IVF and ET to recipients. MAIN OUTCOME MEASURE(S): Recipients' age, body
      mass index (BMI), medical conditions, endometriosis, gravidity, uterine
      pathology, endometrial thickness, egg number, total motile sperm count,
      intracytoplasmic sperm injection (ICSI), zygote number, fertilization rate,
      embryos per ET, embryos frozen, embryo quality, difficulty with transfer, and
      ongoing pregnancies per ET. RESULT(S): Forty-one recipient pairs had discordant
      outcomes. Pregnant patients had a lower frequency (9.7% vs. 31.7%, P=.04) and
      lesser severity of uterine pathology. Endometrium <8 mm was found solely in
      failed cycles. Pregnant women had fewer moderate or difficult ETs (9.7% vs.
      31.7%, P=.04) and more good embryos (1.8 vs. 1.3, P=.03) than the nonpregnant
      group. CONCLUSION(S): Analysis of recipient pairs with discordant outcomes
      identifies the recipient-related predictors of success by keeping oocyte quality
      and the laboratory component constant. Uterine pathology, thin endometrium,
      transfer difficulty, and number of high-grade embryos are the principal recipient
      related determinants of outcome with donor eggs.

PMID- 15482760
TI  - Insemination with isolated and virologically tested spermatozoa is a safe way for
      human immunodeficiency type 1 virus-serodiscordant couples with an infected male
      partner to have a child.
AB  - OBJECTIVE: To enable serodiscordant couples to reproduce while minimizing the
      risk of infecting the female partner and to demonstrate the feasibility of
      including these couples in an insemination program. DESIGN: Prospective follow-up
      study. SETTING: Ambulatory IUIs. PATIENT(S): Fifty-six HIV-1-serodiscordant
      couples with a male infected partner. INTERVENTION(S): Sperm cell separation by
      the gradient density method followed by the swim-up method, virological
      detection, and IUI after ovarian stimulation. MAIN OUTCOME MEASURE(S): Pregnancy
      rate, HIV-1 test, and p24 antigenemia in women. RESULT(S): Two hundred thirteen
      IUIs were performed, and 37 pregnancies occurred, resulting in 33 births and 2
      ongoing pregnancies. Fifty percent of couples have a child. No women were
      infected. CONCLUSION(S): Our study demonstrates the efficiency of an IUI program
      with prepared and virologically tested spermatozoa in serodiscordant couples with
      an HIV-1-infected male partner, allowing the couples to have children without
      transmission of the virus to the female partner.

PMID- 15482761
TI  - Body mass index in relation to semen quality and reproductive hormones among
      1,558 Danish men.
AB  - OBJECTIVE: To examine the relationship between body mass index (BMI) and semen
      quality among young men from the general population. DESIGN: Cross-sectional
      study. SETTING: Danish young men were approached when they attended a compulsory
      physical examination to determine their fitness for military service. PATIENT(S):
      From 1996-1998, 1,558 (19%) young men (mean age 19 years) volunteered. MAIN
      OUTCOME MEASURE(S): Semen volume (in milliliters), sperm concentration (in
      million per milliliter), percentage of motile spermatozoa, percentage of
      spermatozoa with normal morphology, total sperm count (in million), and testis
      size (in milliliters). In addition, serum reproductive hormones were measured.
      RESULT(S): Serum T, sex hormone-binding globulin (SHBG), and inhibin B all
      decreased with increasing BMI, whereas free androgen index and E(2) increased
      with increasing BMI. Serum FSH was higher among slim men. After control for
      confounders, men with a BMI <20 kg/m(2) had a reduction in sperm concentration
      and total sperm count of 28.1% (95% confidence interval [CI] 8.3%-47.9%) and
      36.4% (95% CI 14.6%-58.3%), respectively, and men with a BMI >25 kg/m(2) had a
      reduction in sperm concentration and total sperm count of 21.6% (95% CI 4.0%
      39.4%) and 23.9% (95% CI 4.7%-43.2%), respectively, compared to men with BMI
      between 20-25 kg/m(2). Percentages of normal spermatozoa were reduced, although
      not significantly, among men with high or low BMI. Semen volume and percentage of
      motile spermatozoa were not affected by BMI. CONCLUSION(S): High or low BMI was
      associated with reduced semen quality. It remains to be seen whether the
      increasing occurrence of obesity in the Western world may contribute to an
      epidemic of poor semen quality registered in some of the same countries. If so,
      some cases of subfertility may be preventable.

PMID- 15482762
TI  - Human sperm superoxide anion generation and correlation with semen quality in
      patients with male infertility.
AB  - OBJECTIVE: To measure levels of reactive oxygen species (ROS) including H(2)O(2)
      and O(2)(.-) generation in infertile men and determine whether sperm quality is
      correlated with levels of ROS triggered by the exogenous reduced form of beta
      nicotinamide adenine dinucleotide phosphate (NADPH). DESIGN: Prospective study.
      SETTING: Male infertility clinic at a tertiary healthcare center. PATIENT(S):
      Eleven infertile men and six healthy donors. INTERVENTION(S): Chemiluminescence
      assay using luminol and lucigenin as probes before and after incubating sperm
      samples with 5 mM and 10 mM of NADPH. MAIN OUTCOME MEASURE(S): The ROS generation
      (10(6) counted photons per minute/10(6) sperm). RESULT(S): Baseline levels of
      O(2)(.-) generation were significantly higher in the infertile patients than in
      the healthy donors (r = 0.73, 95% confidence interval [median (25th, 75th
      percentiles): 0.73 (0.5, 5.5) vs. 0.2 (0.0, 0.5)] when lucigenin was used as the
      probe. Compared with basal levels, O(2)(.-) generation was significantly higher
      after coincubation with NADPH (5 mM and 10 mM) in the entire combined study
      population, and patients only but not donors. The O(2)(.-) generation was
      negatively correlated with sperm concentration (r = -0.75, 95% CI 0.38-1),
      motility (r = -0.69, 95% CI 0.28-1), and percentage of normal morphology (r = 
      0.78, 95% CI 0.36-1). CONCLUSION(S): Spermatozoa from infertile men produce
      higher levels of O(2)(.-) in the presence of exogenous NADPH compared to healthy
      donors. The ability of spermatozoa to generate O(2)(.-) increases as the semen
      quality declines.

PMID- 15482763
TI  - Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial.
AB  - OBJECTIVE: To examine the effect on pain and quality of life for women with all
      stages of endometriosis undergoing laparoscopic surgery compared with placebo
      surgery. DESIGN: A randomized, blinded, crossover study. SETTING: A tertiary
      referral unit in a district general hospital. PATIENT(S): Thirty-nine women with
      histologically proven endometriosis completed the 12-month study.
      INTERVENTION(S): Women were randomized to receive initially either a diagnostic
      procedure (the delayed surgical group) or full excisional surgery (the immediate
      surgery group). After 6 months, repeat laparoscopy was performed, with removal of
      any pathology present. MAIN OUTCOME MEASURE(S): The end points were changes from
      baseline values of visual analogue pain scores, validated quality-of-life
      instruments (EQ-5D and SF-12), and sexual activity questionnaire scores. Patients
      and assessors of outcomes were blinded to the treatment-group assignment.
      RESULT(S): Significantly more of the 39 women operated on according to protocol
      reported symptomatic improvement after excisional surgery than after placebo: 16
      of 20 (80%) vs. 6 of 19 (32%); chi(2)(1) = 9.3. Other aspects of quality of life
      were also significantly improved 6 months after excisional surgery but not after
      placebo. Progression of disease at second surgery was demonstrated for women
      having only an initial diagnostic procedure in 45% of cases, with disease
      remaining static in 33% and improving in 22% of cases. Nonresponsiveness to
      surgery was reported in 20% of cases. CONCLUSION(S): Laparoscopic excision of
      endometriosis is more effective than placebo at reducing pain and improving
      quality of life. Surgery is associated with a 30% placebo response rate that is
      not dependent on severity of disease. Approximately 20% of women do not report an
      improvement after surgery for endometriosis.

PMID- 15482764
TI  - Efficacy of the new TwoDay Method of family planning.
AB  - OBJECTIVE: To test the efficacy of the TwoDay Method, a new fertility awareness
      based method of family planning that provides women with simple instructions to
      identify the days each cycle when they are most likely to become pregnant. Users
      avoid unprotected intercourse on days when cervical secretions are present on
      that day or on the day before, to prevent pregnancy. DESIGN: Prospective,
      nonrandomized, multicenter study. SETTING: Five culturally diverse sites in
      Guatemala, Peru, and the Philippines. PATIENT(S): Four hundred fifty women, aged
      18-39 years, wishing to use a fertility awareness-based method to prevent or
      delay pregnancy. INTERVENTION(S): Study participants were followed for up to 13
      cycles of method use. MAIN OUTCOME MEASURE(S): Life table pregnancy rate.
      RESULT(S): The first-year pregnancy rate was 3.5 (pregnancies per 100
      women/years) with correct use of the method (pregnancies and cycles with no
      intercourse on identified fertile days), 6.3 with use of a backup method on the
      fertile days, and 13.7 including all cycles and all pregnancies in the analysis.
      CONCLUSION(S): The TwoDay Method offers a valuable addition to the services that
      reproductive health and other programs can offer. Its efficacy compares well with
      that of other coitus-dependent family-planning methods; it is easy to teach,
      learn, and use; and it can address the need of women for simple, accurate
      instructions for identifying their fertile days.

PMID- 15482765
TI  - Effects of metformin and rosiglitazone, alone and in combination, in nonobese
      women with polycystic ovary syndrome and normal indices of insulin sensitivity.
AB  - OBJECTIVE: To determine whether insulin-sensitizing drugs would improve ovulation
      and T levels in women with polycystic ovary syndrome (PCOS), without clinical or
      biochemical criteria indicating insulin resistance and whether the combination of
      two distinct insulin-sensitizing drugs would be of any benefit over either drug
      alone. DESIGN: Randomized controlled double-blind trial. SETTING: A referral
      center in Caracas, Venezuela. PATIENT(S): One hundred twenty-eight nonobese PCOS
      women with normal indices of insulin sensitivity-that is, normal glucose
      tolerance, fasting insulin, peak insulin during an oral glucose tolerance test
      (OGTT), and fasting glucose-to-insulin ratio. Twenty-eight women were lost to
      follow-up initially and did not receive any intervention. INTERVENTION(S): One
      hundred women received twice daily one of the following for 6 months: metformin
      (850 mg), rosiglitazone (4 mg), combination of both drugs, or at least one
      placebo. MAIN OUTCOME MEASURE(S): Frequencies of ovulation and serum free T after
      6 months. RESULT(S): Frequencies of ovulation were higher after treatment with an
      insulin-sensitizing drug (ovulations per subject in 6 months: metformin, 3.3;
      rosiglitazone, 2.4; and combination, 3.4) than with placebo (0.4). Ovulatory
      frequencies increased significantly more with metformin than rosiglitazone, and
      the combination was not more potent. After treatment, serum free-T levels were
      comparable among all active treatment groups (metformin: 2.34 pg/mL,
      rosiglitazone: 3.06 pg/mL, and combination: 2.39 pg/mL) and were significantly
      lower than in the placebo group (7.26 pg/mL). Compared with placebo, fasting
      insulin levels, area under the insulin curve during OGTT, the homeostatic model
      assessment of insulin sensitivity, and OGTT-derived insulin sensitivity index
      improved significantly after metformin or combination therapies but not after
      rosiglitazone. CONCLUSION(S): These findings suggest that insulin-sensitizing
      drugs increase ovulatory frequency and ameliorate hyperandrogenemia, even in
      nonobese women with PCOS who appear to have normal insulin sensitivity.

PMID- 15482766
TI  - Transdermal estradiol treatment suppresses serum gonadotropins during lactation
      without transfer into breast milk.
AB  - OBJECTIVE: To determine which dose of transdermal E(2) could be administered to
      breastfeeding women without significant transfer into breast milk. DESIGN: Single
      center, prospective study. SETTING: University hospital research unit.
      PATIENT(S): Twenty-one healthy breastfeeding women (aged 20-38 years) who had
      delivered 20 weeks earlier. INTERVENTION(S): Treatment with either 50, 75, or 100
      microg/24 hours of transdermal E(2) or placebo for 2 weeks beginning at 20 weeks
      postpartum. Breast milk and blood samples were collected before the treatment and
      2 weeks into the treatment. MAIN OUTCOME MEASURE(S): Serum and milk E(2) were
      measured by RIA after diethyl ether-ethyl acetate extraction. Serum inhibin B
      concentrations were measured by ELISA and serum FSH and LH concentrations were
      measured by fluoroimmunoassay. RESULT(S): None of the breast milk samples
      contained any measurable concentrations of E(2) after E(2) treatment. Serum E(2)
      concentrations were elevated in a dose-dependent manner. Both serum FSH and LH
      concentrations were decreased in all treatment groups with a more pronounced
      suppression in the 75 and 100 microg/24-hour groups. Serum inhibin B
      concentrations were not significantly suppressed during the study. Three of six
      women using the 100 microg/24-hour E(2) dose discontinued the study due to side
      effects. CONCLUSION(S): A dose as high as 100 microg/24 hours of E(2) can be
      administered transdermally without traces appearing in the breast milk. Whether
      the symptoms associated with the hypoestrogenic state of lactation can be
      alleviated by transdermal E(2) treatment (50 or 75 microg/24 hours) can now be
      studied in the early postpartum phase (6 weeks onward).

PMID- 15482768
TI  - Cryopreservation of human spermatozoa: comparison of two cryopreservation methods
      and three cryoprotectants.
AB  - OBJECTIVE: To evaluate the ability of two cryopreservation methods and three
      cryoprotectants to preserve sperm quality. DESIGN: A prospective clinical study.
      SETTING: Male infertility clinic at a tertiary healthcare center. PATIENT(S):
      Twenty infertile men and 10 healthy donors. INTERVENTION(S): In the first
      experiment, semen was cryopreserved by either the Irvine Scientific method (IS)
      or the Cleveland Clinic Foundation (CCF) method. In the second experiment, semen
      was cryopreserved by the IS method and one of three cryoprotectants: TES and Tris
      yolk buffer, Sperm Freezing Medium, or Enhance Sperm Freeze. MAIN OUTCOME
      MEASURE(S): Postthaw sperm motility, cryosurvival, and kinematics. RESULT(S):
      Percentages of postthaw sperm motility and cryosurvival were higher in the IS
      cryopreservation method compared with in the CCF method (15.94 +/- 9.19 vs. 12.07
      +/- 7.31 and 47.42 +/- 17.44 vs. 35.76 +/- 17.56). However, the CCF method
      resulted in significantly better sperm kinematics. Postthaw motility in the
      donors and patients was highest in the samples frozen in TES and Tris yolk buffer
      medium. CONCLUSION(S): The IS method was associated with more flash freezing
      compared with the CCF method and resulted in better preservation of sperm
      motility and a higher cryosurvival rate. TES and Tris yolk buffer was most
      effective at protecting sperm from the negative effects of the cryopreservation
      process. This may be due to the presence of egg yolk along with glycerol.

PMID- 15482767
TI  - Obstetric implications for and identification of women with a normal clomiphene
      citrate challenge test result who have a poor response to gonadotropins.
AB  - OBJECTIVE: To determine the incidence and obstetric implications and to identify
      prospectively women with a poor response to hMG with a normal clomiphene citrate
      challenge test (CCCT) result. DESIGN: Retrospective chart review. SETTING:
      Tertiary fertility center. PATIENT(S): One hundred sixty-three women who
      underwent ovulation induction with hMG for IUI, and 266 women who underwent
      ovulation induction with GnRH analogue and hMG for IVF. All had a CCCT before
      stimulation. Seventy-five percent of IUI patients (123 of 163) and 89% of IVF
      patients (238 of 266) had normal CCCT results. A poor response to hMG was defined
      as a response less than the 90th percentile of women with an abnormal CCCT result
      (peak E(2) [pg/mL] level per ampule hMG used: 90th percentile </=30).
      INTERVENTION(S): Clomiphene citrate challenge test and ovulation induction for
      IUI or IVF. MAIN OUTCOME MEASURE(S): Response to gonadotropins and pregnancy
      outcome after treatment. RESULT(S): Thirty-five percent of IUI patients (43 of
      123) and 52% of IVF patients (123 of 238) with a normal CCCT result had a poor
      response to hMG. Intrauterine insemination patients with a poor response to hMG
      had significantly lower delivery rates than IUI patients with a normal response
      (19% vs. 39%). In vitro fertilization patients with a poor response to hMG had
      similar delivery rates compared with IVF patients with a normal response (32% vs.
      35%). For both groups of patients, an FSH >12 mIU/mL (IMx assay) on either day 3
      or day 10 (normal </=14.5 IMx) was highly predictive of a poor response to hMG,
      the elevated FSH level being a much better predictor than the woman's age.
      CONCLUSION(S): A poor response to hMG with a normal CCCT result (false negative)
      is a common event. A day-3 or day-10 FSH >12 mIU/mL (IMx assay) or 20 mIU/mL
      (converted to the original RIA) will identify approximately 80% (IUI) and
      approximately 94% (IVF) of the women who will experience a poor response to hMG.
      When identified, the data suggest that these patients will benefit significantly
      from the more aggressive IVF.

PMID- 15482769
TI  - Fluorescence in situ hybridization analysis of human oocytes: advantages of a
      double-labeling procedure.
AB  - OBJECTIVE: To improve the fluorescence in situ hybridization (FISH) chromosomal
      analysis of human oocytes and first polar bodies. DESIGN: In situ chromosomal
      identification on isolated cells, with combinations of centromeric (or locus
      specific) probes and whole-chromosome painting probes for chromosomes 9, 13, 16,
      18, 21, and X. SETTING: Montpellier University Hospital. PATIENT(S): Women
      participating in an IVF program. INTERVENTION(S): Fifty-four in vitro
      unfertilized oocytes were fixed on slides, and simple or double FISH labeling
      procedures were performed on preparations. MAIN OUTCOME MEASURE(S): Simultaneous
      in situ visualization of specific domains and chromosome arms of each targeted
      chromosome. RESULT(S): Eight chromosomal abnormalities were identified, including
      two hyperhaploidies, three cases of extra single chromatid, and three cases of
      balanced separation of sister chromatids. Also, the double-labeling procedure
      allowed the avoidance of five interpretation errors, owing to additional
      artefactual signals. CONCLUSION(S): By ensuring precise identification of both
      chromosomes and single chromatids, the FISH double-labeling procedure limits the
      risk of erroneous interpretation and allows a more accurate cytogenetic analysis
      of human oocytes.

PMID- 15482770
TI  - A nonmosaic 45,X karyotype in a mother with Turner's syndrome and in her
      daughter.
AB  - OBJECTIVE: To describe a woman with a nonmosaic (45,X) form of Turner's syndrome
      who gave birth to a girl with 45,X Turner syndrome. DESIGN: Patient report.
      SETTING: Outpatient clinic of a university hospital. PATIENT(S): A woman with
      typical phenotypic features of Turner syndrome and a 45,X karyotype and her
      daughter with the same karyotype. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Routine karyotype analysis on 200 white blood cells on two different occasions,
      on skin fibroblasts (1,000 mitoses) and on ovarian fibroblasts. Translocation of
      X-chromosome material was investigated by a complete X paint and fluorescent in
      situ hybridization analysis. RESULT(S): The patient had a spontaneous puberty and
      became pregnant on three occasions. Her first daughter has a normal karyotype,
      the second pregnancy ended in spontaneous abortion, and after the third
      pregnancy, a girl was born with a 45,X karyotype. Karyotype analysis of a large
      number of mitoses in three different cell types failed to demonstrate any
      mosaicism. Translocation of X-chromosome material was ruled out by fluorescent in
      situ hybridization analysis with an X paint. CONCLUSION(S): This is a rare case
      of pregnancy in a nonmosaic Turner syndrome patient and, to our knowledge, is the
      only one that resulted in a live-born baby with the same karyotype. Cryptic
      mosaicism could not be found despite thorough investigations. Some hypotheses are
      presented that may explain this unique event.

PMID- 15482771
TI  - Preimplantation genetic diagnosis for polycystic kidney disease.
AB  - OBJECTIVE: To use preimplantation genetic diagnosis for achieving a polycystic
      kidney disease (PKD)-free pregnancy for a couple in which the female partner was
      affected by PKD but whose PKD1 or PKD2 carrier status was not established.
      DESIGN: Case report. SETTING: The IVF program of Reproductive Genetics Institute,
      Chicago, Illinois. PATIENT(S): An at-risk couple with the female partner affected
      by PKD, whose PKD1 or PKD2 carrier status was not established. INTERVENTION(S):
      Removal of PB1 and PB2 and testing for three closely linked markers to PKD1 (Kg8,
      D16S664, and SM7) and four closely linked markers to PKD2 (D4S2922, D4S2458,
      D4S423, and D4S1557) after standard IVF. MAIN OUTCOME MEASURE(S):
      Deoxyribonucleic acid analysis of PB1 and PB2 indicating whether corresponding
      oocytes were PKD1 or PKD2 allele free, for the purpose of transferring only
      embryos resulting from mutation-free oocytes. RESULT(S): Of 11 oocytes tested by
      PB1 and PB2 DNA analysis, 7 were predicted to contain PKD1 or PKD2, with the
      remaining 4 free of both mutations. Three embryos resulting from these oocytes
      were transferred, yielding a twin pregnancy and the birth of two unaffected
      children. CONCLUSION(S): This is the first preimplantation genetic diagnosis for
      PKD, which resulted in the birth of healthy twins confirmed to be free of PKD1
      and PKD2. Preimplantation genetic diagnosis based on linked marker analysis
      provides an alternative for avoiding the pregnancy and birth of children with
      PKD, even in at-risk couples without exact PKD1 or PKD2 carrier information.

PMID- 15482772
TI  - Heterotopic autotransplantation of cryobanked human ovarian tissue as a strategy
      to restore ovarian function.
AB  - OBJECTIVE: To investigate ovarian function after heterotopic autotransplantation
      of human ovarian tissue banked at -196 degrees C. DESIGN: A clinical case study.
      SETTING: University medical center. PATIENT(S): A 37-year-old woman with cervical
      cancer (stage Ib). INTERVENTION(S): Frozen-thawed human ovarian tissue was
      transplanted to two different heterotopic sites. MAIN OUTCOME MEASURE(S): Ovarian
      function of the grafts was monitored sequentially by blood sampling for the
      hormonal profiles and by ultrasound. RESULT(S): The hormonal profile remained at
      the postmenopausal level until 10 weeks after transplantation. By 14 weeks, the
      return of ovarian function was evidenced by the elevation of the serum E(2) level
      (57.5 pg/mL). While monitoring hormonal profiles every 2 days for 5 weeks, we
      observed the LH surge (69.8 IU/L) followed by the elevation of the
      P(4)concentration (9.6 ng/mL), suggesting presumptive ovulation. The ultrasound
      revealed a dominant follicle on the rectus muscle in the abdominal site. However,
      there was no sign of follicle development in the breast site. Ovarian function
      ceased around 28 weeks after transplantation. CONCLUSION(S): Heterotopic
      autotransplantation of cryobanked human ovarian tissue can be a practical
      strategy for restoration of ovarian function after cancer treatment. As a site
      for transplantation, a space between the rectus sheath and the rectus muscle
      appeared to be effective.

PMID- 15482773
TI  - Laparoscopic oophoropexy for the treatment of recurrent torsion of the adnexa in
      pregnancy: case report and review.
AB  - OBJECTIVE: To introduce a new surgical approach, oophoropexy to prevent recurrent
      adnexal torsion. DESIGN: Case report and review of the literature. SETTING: The
      obstetrics and gynecology department of a university hospital. PATIENT(S): A 29
      year-old pregnant patient who had three events of torsion of the adnexa after
      stimulation. INTERVENTION(S): Laparoscopic oophoropexy. MAIN OUTCOME MEASURE(S):
      Incidence of torsion. RESULT(S): No more torsion events were registered during
      the ongoing pregnancy. CONCLUSION(S): Laparoscopic oophoropexy is recommended in
      emergency situations to increase adnexal salvage and to prevent a recurrence.

PMID- 15482774
TI  - Predicted value of renin activity in a woman who had severe ovarian
      hyperstimulation syndrome with internal jugular vein thrombosis.
AB  - OBJECTIVE: To assess plasma renin activity in a patient with severe ovarian
      hyperstimulation syndrome (OHSS) and internal jugular vein thrombosis. DESIGN:
      Case report. SETTING: University-affiliated infertility center. PATIENT(S): A 33
      year-old woman with OHSS and internal jugular vein thrombosis. INTERVENTION(S):
      Controlled ovulation hyperstimulation with recombinant FSH induction. MAIN
      OUTCOME MEASURE(S): Plasma renin activity (PRA), color Doppler ultrasound of the
      neck. RESULT(S): The patient had internal jugular vein thrombosis caused by
      severe OHSS. The PRA was significantly elevated during the acute stage and
      subsequently declined after resolution of the OHSS. CONCLUSION(S): In this
      patient elevated PRA appeared to be associated with the development of OHSS and
      thrombosis. The implication of the ovarian renin-angiotensin system in the
      development of OHSS and thrombosis is relevant.

PMID- 15482775
TI  - Maternal complication of cervical heterotopic pregnancy after successful
      potassium chloride fetal reduction.
AB  - OBJECTIVE: To present a case of maternal morbidity encountered in a cervical
      heterotopic pregnancy after successful potassium chloride (KCl) injection for
      transvaginal multifetal pregnancy reduction. DESIGN: Case report. SETTING:
      Tertiary referral care center. PATIENT(S): A woman with heterotopic twin
      gestation after IVF. INTERVENTION(S): Diagnosis of a viable cervical heterotopic
      pregnancy was made at 6 weeks by ultrasound. A transvaginal reduction by KCl
      injection of the cervical pregnancy was performed under sonographic guidance.
      MAIN OUTCOME MEASURE(S): Maternal morbidity and mortality. RESULT(S): Although
      contents of the gestational sac within the cervix resolved, the trophoblastic
      tissue increased in both size and vascularity. The patient continued to have self
      limited vaginal bleeding throughout the pregnancy. However, at 31 weeks, she had
      an acute hemorrhage, resulting in an emergency cesarean hysterectomy secondary to
      profuse bleeding from retained cervical trophoblastic tissue. CONCLUSION(S):
      Although KCl transvaginal multifetal pregnancy reduction might successfully
      terminate a cervical heterotopic pregnancy, the ongoing pregnancy might be
      complicated by persistence and even enlargement of remaining trophoblastic
      tissue, leading to obstetric hemorrhage.

PMID- 15482776
TI  - A mesothelial cyst of the round ligament presenting as an inguinal hernia after
      gonadotropin stimulation for in vitro fertilization.
AB  - OBJECTIVE: To report the case of a round ligament cyst which, as the result of
      gonadotropin stimulation for IVF, simulated an incarcerated inguinal hernia.
      DESIGN: Case report. SETTING: A private infertility center and a university
      hospital. PATIENT(S): A 31-year-old woman who developed left lower quadrant pain
      after gonadotropin stimulation for IUI and a tender left inguinal mass after
      increasing ovarian stimulation for IVF/intracytoplasmic sperm injection.
      INTERVENTION(S): Surgical excision of a mesothelial cyst of the left round
      ligament and exploration of the left inguinal canal. MAIN OUTCOME MEASURE(S):
      Successful surgical excision of left inguinal mass. RESULT(S): Resolution of
      symptoms. CONCLUSION(S): Mesothelial cysts of the round ligament should be
      included in the differential diagnosis of inguinal masses in women. Gonadotropin
      stimulation might cause previously unrecognized cysts to simulate an incarcerated
      inguinal hernia, necessitating surgical repair.

PMID- 15482777
TI  - The necessity of complete CFTR mutational analysis of an infertile couple before
      in vitro fertilization.
AB  - OBJECTIVE: To determine the genotype of a triplet resulted from an IVF procedure,
      with discordant cystic fibrosis (CF) phenotype. DESIGN: Molecular diagnosis of
      CF. SETTING: Affected triplet followed at the CF Clinic Center of Children's
      Hospital Los Angeles was referred to Molecular Genetics Laboratory at Georgetown
      University Medical Center for comprehensive DNA analysis of the cystic fibrosis
      transmembrane regulator (CFTR) gene. PATIENT(S): Three affected children and the
      healthy parents with negative family history of CF. MAIN OUTCOME MEASURE(S):
      Temporal temperature gradient gel electrophoresis and direct DNA sequencing were
      used to detect and to identify the mutations. RESULT(S): The child with classic
      CF had DeltaF508 and R553X mutations. Two children with mild CF symptoms had
      DeltaF508 and R117C. The father carried two mutations, R553X and R117C. The
      mother is a carrier for DeltaF508. CONCLUSION(S): Mutational analysis of the CFTR
      gene should always be recommended to the infertile couples seeking for IVF. The
      CFTR mutation screening would be essential if the man has congenital bilateral
      absence of vas deferens (CBAVD) despite the negative family history of CF. Option
      of complete CFTR gene analysis at a cost of about 1,500-2,000 dollars should be
      made available if one mutation is found in the male partner with congenital
      bilateral absence of vas deferens.

PMID- 15482778
TI  - An unusual anatomic variation of a unicornuate uterus with normal external
      uterine morphology.
AB  - OBJECTIVE: To describe a case of a unicornuate uterus with a normal external
      uterine morphology. DESIGN: Case report. SETTING: University-based fertility
      center. PATIENT(S): A 30-year-old nulligravid woman with a 1-year history of
      infertility found to have a right proximal tubal occlusion on
      hysterosalpingogram. INTERVENTION(S): Laparoscopy, hysteroscopy, and magnetic
      resonance imaging. MAIN OUTCOME MEASURE(S): External and internal morphology of
      the uterus. RESULT(S): Laparoscopy showed a normal external uterine morphology
      and normal fallopian tubes and ovaries, but chromopertubation failed to
      demonstrate a fill and spill from the right fallopian tube. Hysteroscopy showed a
      single tubular uterine cavity projecting to the left with a single left tubal
      ostium, consistent with a unicornuate uterus. Magnetic resonance imaging
      confirmed a normal external uterine fundal contour and an internal uterine
      morphology consistent with a unicornuate uterus. CONCLUSION(S): This is the first
      reported case of a unicornuate uterus presenting with a normal external uterine
      morphology and an internal morphology consistent with a unicornuate uterus, and
      we propose inclusion of this anomaly in the classification of mullerian
      anomalies.

PMID- 15482779
TI  - Fresh autologous transplantation of ovarian cortical strips to the anterior
      abdominal wall at the pfannenstiel incision site.
AB  - OBJECTIVE: To describe an open surgical technique for transplanting fresh ovarion
      tissue to the anterior abdominal wall at the incision site and to determine
      whether ovarian function would be restored after transplantation. DESIGN: Case
      study. SETTING: Academic medical center. PATIENT(S): A 44-year-old patient who
      underwent an operation for uterine fibroids. INTERVENTION(S): Microsurgical
      reconstruction of ovarian cortex and its transplantation to the anterior
      abdominal wall at incision site of Pfannenstiel. MAIN OUTCOME MEASURE(S):
      Follicular development evident by ultrasound examination; restoration of serum
      FSH and LH levels to nonmenopausal range; and disappearance of menopausal
      symptoms. RESULT(S): Early postoperative FSH, LH, and E(2) levels showed that
      menopause was confirmed. Postoperative hormone levels at months 2, 3, and 6 were
      as follows: FSH: 77.86, 79.50, and 13.70 mIU/mL; LH: 34.60, 33.92, and 8.78
      mIU/mL; E(2): 29, 46, and 48 pg/mL. The patient is still followed-up for
      postmenopausal status. CONCLUSION(S): Autotransplantation of cortical strips to
      the anterior abdominal wall at the incision site without further incision can be
      a logical solution for the patients at early climacteric age.

PMID- 15482780
TI  - An interclass nuclear transfer between fowl and mammal: in vitro development of
      chicken-to-cattle interclass embryos and the detection of chicken genetic
      complements.
AB  - An attempt was made to develop an interclass somatic cell nuclear transfer method
      as an alternative means of establishing chicken embryonic stem cells. Chicken-to
      cattle interclass embryos that activated calcium ionophore, cycloheximide, and
      cytochalasin D were developed into blastocysts, and the developing interclass
      embryos had chicken genetic complements.

PMID- 15482781
TI  - An optimized protocol of a human-to-cattle interspecies somatic cell nuclear
      transfer.
AB  - Human somatic cells were transferred into cattle enucleated oocytes, and a
      prospective, randomized study was designed to optimize donor cell preparation,
      fusion medium, and culture method. As a result, improved development of
      interspecies embryos was achieved by employing serum-starved cord fibroblasts,
      with Ca(2+)/Mg(2+)-free fusion medium and a serum-free medium being used for
      bovine embryos.

PMID- 15482782
TI  - Development of a nonmechanical enucleation method using x-ray irradiation in
      somatic cell nuclear transfer.
AB  - Irradiation of in-vitro-matured bovine oocytes with x-rays of different durations
      was performed to develop an alternative to conventional mechanical enucleation
      methods in somatic cell nuclear transfer. No significant difference in embryo
      development to the blastocyst stage was detected between nonmechanical and
      mechanical methods, and cytologic analyses of karyotype and microtubule formation
      showed the potential availability of x-ray irradiation.

PMID- 15482783
TI  - Midluteal matrix metalloproteinase and tissue-inhibiting metalloproteinase plasma
      levels after embryo transfer.
AB  - This study demonstrates significant differences in the midluteal concentrations
      of active matrix metalloproteinase (MMP)-1, MMP-2, and total MMP-3 between
      patients who conceived and those who did not after day 3 ET.

PMID- 15482784
TI  - A pilot study of the relationship between selective serotonin reuptake inhibitors
      and in vitro fertilization outcome.
AB  - In a retrospective chart review study women taking selective serotonin reuptake
      inhibitors antidepressants were compared with a matched comparison group to
      determine whether there were any differences in IVF outcome-related variables.
      There were no significant differences between the groups in peak E(2), number of
      oocytes retrieved, number of oocytes fertilized, percentage of 8-cell or
      blastocysts developed, day of transfer, or initial hCG values; however, 40% of
      women taking selective serotonin reuptake inhibitors had ongoing pregnancies
      compared to 51% of women not taking selective serotonin reuptake inhibitors.

PMID- 15482785
TI  - Mullerian-inhibiting substance in women with polycystic ovary syndrome:
      relationship with hormonal and metabolic characteristics.
AB  - The aim of the present study was to examine the relationship between Mullerian
      inhibiting substance (MIS) levels and metabolic characteristics in women with
      polycystic ovary syndrome. Increased ovarian MIS production may exert a paracrine
      negative control on follicle growth sufficiently to prevent selection of a
      dominant follicle.

PMID- 15482786
TI  - Role of a CYP17 polymorphism in the regulation of circulating
      dehydroepiandrosterone sulfate levels in women with polycystic ovary syndrome.
AB  - We studied 259 consecutive unselected white patients with the polycystic ovary
      syndrome (PCOS) and 161 matched controls for a common polymorphism of CYP17, the
      gene encoding for P450c17alpha, and did not observe an important modulatory
      effect of this variant on circulating DHEAS. It does not appear that this common
      variant of CYP17, a T to C substitution in the 5' promoter region, plays a
      significant role in the adrenal androgen excess of PCOS.

PMID- 15482787
TI  - Reliability and validity of an objective assessment instrument of laparoscopic
      skill.
AB  - A novel objective assessment method in reproductive endoscopic surgery could
      advance surgical education.

PMID- 15482788
TI  - Characteristics of baseline ovarian cysts in clomiphene citrate ovulation cycles.
AB  - To evaluate the incidence and factors associated with ovarian cysts in infertile
      patients receiving clomiphene citrate (CC), we performed a retrospective cohort
      study involving 466 CC treatment cycles. Ovarian cysts are a common finding in
      patients presenting for CC, with approximately one in five patients having a
      baseline ovarian cyst >10 mm.

PMID- 15482789
TI  - Protein Z levels and unexplained fetal losses.
AB  - We evaluated protein Z plasma levels in a group of women with fetal losses (n =
      124) and compared them with those in a group of women (n = 60) with uneventful
      pregnancies. We found that protein Z deficiency is not associated with otherwise
      unexplained fetal losses.

PMID- 15482790
TI  - Expression of platelet endothelial cell adhesion molecule-1 in red and black
      endometriotic lesions.
AB  - This immunohistochemical study shows that platelet endothelial cell adhesion
      molecule-1 (PECAM-1), known to play a role in neoangiogenesis and vascular
      development, is strongly and homogeneously expressed in endothelial cells lining
      blood vessels from red and black pelvic endometriotic lesions. The distribution
      of PECAM-1 within the stroma of the lesions was similar to that found in the
      corresponding eutopic endometrium, regardless of the phase of the cycle.

PMID- 15482792
TI  - "Triple marker" for ectopic pregnancy.

PMID- 15482793
TI  - Units of analysis-matched pairs, single patient, or cycles?

PMID- 15482794
TI  - The guinea pig model for uterine leiomyomata: gene-hormone interaction?

PMID- 15482796
TI  - The guinea pig model for uterine leiomyomata: gene-hormone interaction?

PMID- 15482797
TI  - Ovarian tissue and oocyte cryopreservation.
AB  - Although currently investigational, ovarian tissue cryopreservation and oocyte
      cryopreservation hold promise for future female fertility preservation,
      particularly following aggressive chemotherapy and/or radiotherapy treatment
      protocols.

PMID- 15482798
TI  - Local and non-local deficits in amblyopia: acuity and spatial interactions.
AB  - Amblyopic vision is thought to be limited by abnormal long-range spatial
      interactions, but their exact mode of action and relationship to the main
      amblyopic deficit in visual acuity is largely unknown. We studied this
      relationship in a group (N=59) of anisometropic (N=21) and strabismic (or
      combined, N=38) subjects, using (1) a single and multi-pattern (crowded)
      computerized static Tumbling-E test with scaled spacing of two pattern widths
      (TeVA), in addition to an optotype (ETDRS chart) acuity test (VA) and (2)
      contrast detection of Gabor patches with lateral flankers (lateral masking) along
      the horizontal and vertical axes as well as in collinear and parallel
      configurations. By correlating the different measures of visual acuity and
      contrast suppression, we found that (1) the VA of the strabismic subjects could
      be decomposed into two uncorrelated components measured in TeVA: acuity for
      isolated patterns and acuity reduction due to flanking patterns. The latter
      comprised over 60% of the VA magnitude, on the average and accounted for over 50%
      of its variance. In contrast, a slight reduction in acuity was found in the
      anisometropic subjects, and the acuity for a single pattern could account for 70%
      of the VA variance. (2) The lateral suppression (contrast threshold elevation) in
      a parallel configuration along the horizontal axis was correlated with the VA
      (R2=0.7), as well as with the crowding effect (TeVA elevation, R2=0.5) for the
      strabismic group. Some correlation with the VA was also found for the collinear
      configuration in the anisometropic group, but less suppression and no correlation
      were found for all the vertical configurations in all the groups. The results
      indicate the existence of a specific non-local component of the strabismic
      deficit, in addition to the local acuity deficit in all amblyopia types. This
      deficit might reflect long-range lateral inhibition, or alternatively, an
      inaccurate and scattered top-down attentional selection mechanism.

PMID- 15482799
TI  - Sensitivity to linear-speed-gradient of radial expansion flow in infancy.
AB  - A radial expansion flow having a linear-speed-gradient (linear-grad) creates
      robust perception of a rigid object moving-in-depth [Perception 19 (1990) 21]. It
      has been reported that sensitivity to a linear-grad of radial expansion emerges
      at 2 months of age [Infant Behavior and Development 17 (1994) 165]. In the
      present study, we examined the development of sensitivity to the linear-grad of
      radial expansion after 2 months of age with three experiments. A total of 197 2-
      to 5-month-old infants participated. The results showed that sensitivity to the
      linear-grad improves between 2 and 3 months of age (Experiment 1), and that the
      infants may discriminate between an expansion having linear-grad and that having
      zero-grad based on their perception of motion-in-depth (Experiments 2 and 3).

PMID- 15482800
TI  - Accommodation as a function of age and the linearity of the response dynamics.
AB  - The changes with age in the accommodation responses to dynamic stimuli can reveal
      useful information on the factors underlying presbyopia development. Analysis of
      the monocular accommodation responses of 19 normal observers (ages 18-49 years)
      to stimuli whose vergence varied sinusoidally with time at different temporal
      frequencies (peak-to-peak stimulus 1.33-2.38 D, at 0.05-1.00 Hz) showed that at
      all ages both the gain and phase of the response were essentially linear
      functions of the temporal frequency. Extrapolation of least-squares, regression
      line fits to the gain data for each subject gave the gain at zero frequency, G0,
      and the cut-off frequency, fc, at which the gain fell to zero. G0 reduced with
      age but fc remained essentially constant at about 1.7 Hz, up to at least the age
      of about 40. The magnitude of the response to step stimuli covering the same
      stimulus range was well correlated with the value of G0. The linear changes in
      phase lag with temporal frequency corresponded to simple time delays td. The time
      lag varied from close to zero for the youngest subjects to about 0.5 s for the
      subjects in their late forties. There was substantial variation between the
      responses of subjects of similar age: those subjects with high values of G0 also
      tended to have low values of td, both effects probably being due to the superior
      ability of some individuals to predict the sinusoidal changes in the
      accommodation stimulus. Comparison of theoretical step responses, derived by
      applying linear theory to the parameters obtained from the results for the
      sinusoidal stimuli, with the actual responses to unpredictable steps for the same
      subjects supports the view that prediction effects and other possible factors
      make linear theory inapplicable to this type of data. The results are discussed
      in the context of current ideas on the development of presbyopia: it is suggested
      that the constancy of fc with age is the result of the ciliary body maintaining
      its efficiency, whereas the fall in G0 and increase in td result from increases
      in lens rigidity.

PMID- 15482801
TI  - Valences in contextual vision.
AB  - Elements in the neighborhood of a stimulus can modulate both the subjective
      perception of and the neural responses to this stimulus. Investigations of this
      contextual modulation usually focus on low level features such as the orientation
      difference between the target and its context. Recently, we introduced a paradigm
      in which contextual modulation cannot be explained by orientation differences
      between target and context per se. Instead, the overall structure of the context
      seemed to determine contextual modulation. Here, we show that edges of contextual
      gratings as well as isolated contextual lines are the main source of contextual
      suppression in this effect. Such suppressive contextual elements can be blocked
      by non-suppressive ones. We suggest that contextual elements reveal valences in
      loose analogy to chemical valences.

PMID- 15482802
TI  - Is there opponent-orientation coding in the second-order channels of pattern
      vision?
AB  - Is there opponency between orientation-selective processes in pattern perception,
      analogous to opponency between color mechanisms? Here we concentrate on possible
      opponency in second-order channels. We compare several possible second-order
      structures: SIGN-opponent-only channels in which there is no opponency between
      orientations (also called complex channels or filter-rectify-filter mechanisms);
      three structures we group under the name ORIENTATION-opponent; and finally BOTH
      opponent channels which combine features of both SIGN-opponent-only and
      ORIENTATION-opponent channels but lead to predictions that are distinct from
      either of theirs. We measured observers' ability to segregate textures composed
      of checkerboard and striped arrangements of vertical and horizontal Gabor grating
      patches. The observers' performance was compared to model predictions from the
      alternative opponent structures. The experimental results are consistent with
      SIGN-opponent-only channels. The results rule out the ORIENTATION-opponent and
      BOTH-opponent structures. Further, when the models were expanded to include a
      contrast gain-control (inhibition among channels in a normalization network) the
      SIGN-opponent-only model was also able to explain a contrast-dependent effect we
      found, thus providing another piece of evidence that such normalization is an
      important process in human texture perception.

PMID- 15482803
TI  - Figure-ground segregation can rely on differences in motion direction.
AB  - If the elements within a figure move synchronously while those in the surround
      move at a different time, the figure is easily segregated from the surround and
      thus perceived. Lee and Blake (1999) [Visual form created solely from temporal
      structure. Science, 284, 1165-1168] demonstrated that this figure-ground
      separation may be based not only on time differences between motion onsets, but
      also on the differences between reversals of motion direction. However, Farid and
      Adelson (2001) [Synchrony does not promote grouping in temporally structured
      displays. Nature Neuroscience, 4, 875-876] argued that figure-ground segregation
      in the motion-reversal experiment might have been based on a contrast artefact
      and concluded that (a)synchrony as such was 'not responsible for the perception
      of form in these or earlier displays'. Here, we present experiments that avoid
      contrast artefacts but still produce figure-ground segregation based on purely
      temporal cues. Our results show that subjects can segregate figure from ground
      even though being unable to use motion reversals as such. Subjects detect the
      figure when either (i) motion stops (leading to contrast artefacts), or (ii)
      motion directions differ between figure and ground. Segregation requires minimum
      delays of about 15 ms. We argue that whatever the underlying cues and mechanisms,
      a second stage beyond motion detection is required to globally compare the
      outputs of local motion detectors and to segregate figure from ground. Since
      analogous changes take place in both figure and ground in rapid succession, this
      second stage has to detect the asynchrony with high temporal precision.

PMID- 15482804
TI  - Temporal aspects of spatial interactions affecting stereo-matching solutions.
AB  - Stereo-matching solutions minimize disparity relative to the horopter (minimum
      absolute-disparity or MAD), and differences in disparity between adjacent
      features (minimum-relative-disparity or MRD). When placed in conflict, spatial
      proximity promotes MRD over MAD solutions. How does temporal proximity of
      neighboring features affect strength of these spatial interactions? We quantified
      the inter-stimulus interval (ISI) over which an unambiguous disparity pattern
      influenced stereo-matches for patterns with several possible solutions.
      Likelihood of MRD decreased as ISI increased (48.9 ms time constant) and
      increased as contrast was reduced for short ISIs, suggesting that monocular
      persistence (temporal impulse response) underlies the temporal interaction.

PMID- 15482805
TI  - Facilitation of contrast detection in near-peripheral vision.
AB  - Foveal detection of a Gabor patch (target) is facilitated by collinear, displaced
      high-contrast flankers. Polat and Sagi reported that the same phenomenon occurred
      in the periphery, but no data were presented [Proc. Natl. Acad. Sci. 91 (1994)
      1206]. Others have found no facilitation in a limited number of conditions
      tested. To resolve this apparent conflict, we measured lateral facilitation in
      the near-periphery using a range of stimulus parameters. We found facilitation
      for a range of target-flanker distances for peripheral eccentricities up to 6
      degrees , but the magnitude of the effect was less than found in central vision.
      Facilitation varied across subjects and with spatial frequency. Flanker contrast
      had no effect over the range evaluated (10-80%). Equal facilitation was found for
      two global arrangements of the stimulus pattern. Facilitation was found using a
      temporal, but not a spatial two-alternative forced-choice paradigm, accounting
      for the different results among previous studies. This finding supports previous
      indications of the role of attention in altering such facilitation. The value of
      facilitation from lateral interactions for persons with central vision
      impairment, who have to shift their attention to a peripheral locus constantly,
      needs to be examined.

PMID- 15482806
TI  - Transient lumanopia at high intensities.
AB  - Transient lumanopia is the loss of sensitivity to a flicker burst presented in
      early dark adaptation. We earlier reported that lumanopia with 18 Hz flicker was
      greatest after turning off 400 td adapting fields and progressively disappeared
      as the adapting field was intensified. We now report that lumanopia can occur
      with intense adapting fields, but only with faster flickers (e.g. 40 Hz, 5000 td
      fields). Dimming the field (but not brightening it) can also produce lumanopia.
      The results illustrate frequency-dependent attenuation by a temporal filter whose
      parameters are set by light adaptation and which change abruptly when the field
      is dimmed or extinguished.

PMID- 15482807
TI  - The effects of eye movements, spatial attention, and stimulus features on
      inattentional blindness.
AB  - Observers often fail to detect the appearance of an unexpected visual object
      ("inattentional blindness"). Experiment 1 studied the effects of fixation
      position and spatial attention on inattentional blindness. Eye movements were
      measured. We found strong inattentional blindness to the unexpected stimulus even
      when it was fixated and appeared in one of the expected positions. The results
      suggest that spatial attention is not sufficient for attentional capture and
      awareness. Experiment 2 showed that the stimulus was easier to consciously detect
      when it was colored but the relation of the color to the color of the attended
      objects had no effect on detection. The unexpected stimulus was easiest to
      detect, when it represented the same category as the attended objects.

PMID- 15482808
TI  - A visual mechanism tuned to black.
AB  - Chubb et al. [Journal of the Optical Society of America A 11 (1994) 2350]
      investigated preattentive discrimination of achromatic textures comprising random
      mixtures of 17 Weber contrasts ranging linearly from -1 to 1. They showed that
      only a single mechanism B is used to discriminate between textures whose
      histograms are equated in mean and in variance. Although they provided a partial
      characterization of B, their methods did not allow them to measure the
      sensitivity of B to texture mean and variance. Here, additional measurements are
      performed to complete the functional characterization of B. The results reveal
      that B (i) is strongly activated by texture elements of the lowest contrast (near
      -1), (ii) is slightly activated by texture elements of contrast -0.875, and (iii)
      barely distinguishes the 15 contrasts ranging from -0.75 all the way up to 1. To
      reflect the sharpness of its tuning to very dark, sparse elements in a
      predominantly bright scene, we call B the blackshot mechanism.

PMID- 15482809
TI  - Biomarker discovery using molecular profiling approaches.

PMID- 15482810
TI  - Proteomic analysis of mitochondrial proteins.

PMID- 15482811
TI  - NMDA receptors, neural pathways, and protein interaction databases.

PMID- 15482812
TI  - Dopamine transporter network and pathways.

PMID- 15482813
TI  - Proteomic approaches in drug discovery and development.

PMID- 15482814
TI  - Proteomic informatics.

PMID- 15482815
TI  - Proteomics analysis in Alzheimer's disease: new insights into mechanisms of
      neurodegeneration.

PMID- 15482816
TI  - Proteomics and alcoholism.

PMID- 15482817
TI  - Proteomics studies of traumatic brain injury.

PMID- 15482818
TI  - Influence of Huntington's disease on the human and mouse proteome.

PMID- 15482819
TI  - Proteomics--application to the brain.

PMID- 15482820
TI  - Development of highly reactive mono-(meth)acrylates as reactive diluents for
      dimethacrylate-based dental resin systems.
AB  - Reactive diluents such as triethyleneglycol-dimethacrylate (TEGDMA) have been
      widely used with bisphenol-A-glycidyl-dimethacrylate (Bis-GMA) to achieve
      restorative resins with appropriate viscosity and higher conversion. However,
      additional water sorption and polymerization shrinkage were also introduced. The
      aim of this work is to investigate whether the cure and material properties can
      be improved in dental resins containing novel mono-(meth)acrylates as reactive
      diluents so that these Bis-GMA-based copolymers have reduced polymerization
      shrinkage but higher overall double bond conversion. Several ultra-high
      reactivity mono-(meth)acrylates that contain secondary functionalities have been
      synthesized and investigated. The polymerization rate and double bond conversion
      were monitored using photo-FTIR. Polymerization shrinkage, dynamic mechanical
      analysis, and flexural strength were characterized. Compared with the Bis
      GMA/TEGDMA control, the Bis-GMA/mono-methacrylate systems studied showed higher
      final conversions, faster curing rates, and decreased polymerization shrinkage.
      Our optimum system Bis-GMA/morpholine carbamate methacrylate achieved 86% final
      conversion (vs. 65%), a polymerization rate 3.5 times faster, and a 30% reduction
      in polymerization volumetric shrinkage. These results indicate that certain
      highly reactive, novel mono-(meth)acrylates possess very promising potential to
      replace TEGDMA as reactive diluents and can readily be applied to develop
      superior dental resins.

PMID- 15482821
TI  - Fast setting calcium phosphate-chitosan scaffold: mechanical properties and
      biocompatibility.
AB  - Calcium phosphate cement (CPC) sets in situ to form hydroxyapatite and is highly
      promising for a wide range of clinical applications. However, its low strength
      limits its use to only non-stress applications, and its lack of macroporosity
      hinders cell infiltration, bone ingrowth and implant fixation. The aim of this
      study was to develop strong and macroporous CPC scaffolds by incorporating
      chitosan and water-soluble mannitol, and to examine the biocompatibility of the
      new graft with an osteoblast cell line and an enzymatic assay. Two-way ANOVA
      identified significant effects on mechanical properties from chitosan
      reinforcement and powder:liquid ratio (p<0.001). The flexural strength of CPC
      chitosan composite at a powder:liquid ratio of 2 was (13.6+/-1.2) MPa, which was
      significantly higher than (3.2+/-0.6) MPa for CPC control without chitosan
      (Tukey's at 0.95). At a powder:liquid ratio of 3.5, CPC-chitosan had a strength
      of (25.3+/-2.9) MPa, which was significantly higher than (10.4+/-1.7) MPa for CPC
      control. The scaffolds possessed total pore volume fractions ranging from 42.0%
      to 80.0%, and macroporosity up to 65.5%. At total porosities of 52.2-75.2%, the
      scaffold had strength and elastic modulus values similar to those of sintered
      porous hydroxyapatite and cancellous bone. Osteoblast mouse cells (MC3T3-E1) were
      able to adhere, spread and proliferate on CPC-chitosan specimens. The cells,
      which ranged from about 20 to 50 microm including the cytoplasmic extensions,
      infiltrated into the 165-271 microm macropores of the scaffold. In summary,
      substantial reinforcement and macroporosity were imparted to a moldable, fast
      setting, biocompatible, and resorbable hydroxyapatite graft. The highly porous
      scaffold may facilitate bone ingrowth and implant fixation in vivo. In addition,
      the two to three times increase in strength may help extend the use of CPC to
      larger repairs in moderately stress-bearing locations.

PMID- 15482822
TI  - Enhanced osteoblast adhesion on hydrothermally treated
      hydroxyapatite/titania/poly(lactide-co-glycolide) sol-gel titanium coatings.
AB  - Sol-gel processing was used to coat titanium substrates with hydroxyapatite (HA),
      TiO2, and poly(DL-lactic-glycolic acid). Coating surface characteristics were
      analyzed with XRD, EDS, AFM, SEM, and water contact angle measurements which
      indicated that the coatings had a high degree of crystallinity and good
      resistance to cracking. Coatings were also evaluated by cytocompatibility testing
      with osteoblast-like cells (or bone-forming cells). The cytocompatibility of the
      HA composite coatings prepared in the present in vitro study was compared to that
      of a traditional plasma-sprayed HA coating. Results showed that osteoblast-like
      cell adhesion was promoted on the novel HA sol-gel coating compared to the
      traditional plasma-sprayed HA coating. In addition, hydrothermal treatment of the
      sol-gel coating improved osteoblast-like cell adhesion. Since osteoblast adhesion
      is a necessary prerequisite for subsequent formation of bone, these results
      provided evidence that hydrothermally sol-gel processed HA may improve bonding of
      titanium implants to juxtaposed bone and, thus, warrants further investigation.

PMID- 15482823
TI  - Degradation of poly(lactide-co-glycolide) (PLGA) and poly(L-lactide) (PLLA) by
      electron beam radiation.
AB  - This paper seeks to examine the effects of electron beam (e-beam) radiation on
      biodegradable polymers (PLGA and PLLA), and to understand their radiation-induced
      degradation mechanisms. PLGA (80:20) and PLLA polymer films were e-beam
      irradiated at doses from 2.5 to 50 Mrad and the degradation of these films were
      studied by measuring the changes in their molecular weights, FTIR spectra,
      thermal and morphological properties. The dominant effect of e-beam irradiation
      on both PLGA and PLLA is chain scission. Chain scission occurs first through
      scission of the polymer main chain, followed by hydrogen abstraction. Chain
      scission, though responsible for the reduction in the average molecular weight,
      Tc, Tg and Tm of both polymers, encourages crystallization in PLGA. PLLA also
      undergoes chain scission upon irradiation but to a lesser degree compared to
      PLGA. The higher crystallinity of PLLA is the key factor in its greater stability
      to e-beam radiation compared to PLGA. A linear relationship is also established
      between the decrease in molecular weight with respect to radiation dose.

PMID- 15482824
TI  - Mechanical properties, proteolytic degradability and biological modifications
      affect angiogenic process extension into native and modified fibrin matrices in
      vitro.
AB  - During initial stages of wound healing, fibrin clots provide a three-dimensional
      scaffold that induces cell infiltration and regeneration. Here, L1Ig6, a ligand
      for alphavbeta3 integrin was covalently incorporated within fibrin matrices to
      explore it as a matrix-immobilized angiogenic factor. Incorporation at
      concentrations greater than 1 microg/ml reduced the fibrin crosslink density, as
      reflected by measurements of elastic modulus and swelling. The influence of
      crosslink density on endothelial cell process extension was characterized by
      modulating factor XIII concentrations in the coagulation mixture. At low
      incorporated concentrations of L1Ig6, it was possible to compensate gel elastic
      modulus via increased factor XIII, but not at high concentrations of L1Ig6.
      Similar findings were found when matrix swelling was analyzed. Fibrin crosslink
      density strongly influenced endothelial cell process extension, fewer and shorter
      processes were observed at high crosslink density. Matrix metalloproteinases
      (MMPs) were required for process extension and zymography and Western blots
      identified MMP-2 but not MMP-9. The amount of active MMP-2 increased for
      endothelial cells cultured in native and L1Ig6-modified matrices or when
      stimulated with VEGF-A165. The data indicate that distinct matrix properties can
      be tailored such that they become biologically stimulating and respond to
      cellular proteolytic activities, being a prerequisite for potential use of such
      matrices in biomedical applications.

PMID- 15482825
TI  - Photo-immobilization of a phospholipid polymer for surface modification.
AB  - A photo-reactive polymer having a phospholipid polar group was prepared, and the
      polymer was photo-immobilized on polymeric surfaces, where its interactions with
      biocomponents were investigated. By using a photo-immobilization method, the
      polymer was used for surface modification of polyethylene and polypropylene,
      polymers whose surfaces were not treated in our previous development of the
      phosphorylcholine-derived polymer. The photo-reactive polymer was synthesized by
      a coupling reaction involving copolymer consisting of 2-methacryloyloxyethyl
      phosphorylcholine and methacrylic acid with 4-azidoaniline. When the polymer was
      unpattern immobilized on the surface, X-ray photo-electron spectroscopic analysis
      and static contact angle measurements were performed. It was shown that the
      surface was covered with phospholipid polar groups. Micropattern immobilization
      was carried out using a micropatterned photo-mask. Measurements using atomic
      force microscopy showed that the swelled micropatterned polymer was five times as
      thick as the dried one. Protein adsorption and platelet adhesion were reduced on
      the polymer-immobilized regions. Mammalian cells did not adhere, and formed
      aggregates on the immobilized regions. In conclusion, the photo-reactive
      phospholipid polymer was covalently immobilized on the conventional polymer
      surfaces and it tended to reduce interactions with proteins and cells.

PMID- 15482826
TI  - The tissue response to an alkylene bis(dilactoyl)-methacrylate bone adhesive.
AB  - Gluing is an attractive technique to fix small bone fragments. However, to date
      no bone adhesive could be established successfully for all day clinical use. The
      purpose of this experimental study was to investigate the biocompatibility of a
      new bone glue based on alkylene bis(dilactoyl)-methacrylate in 36 rabbits.
      Monocondylar osteotomy of the distal femur was performed and bone glue was
      applied into the osteotomy gap in 24 rabbits. The remaining 12 animals served as
      controls. In all rabbits the osteotomy was subsequently stabilized by K-wire
      osteosynthesis. Six animals of the glue group and 3 controls were euthanized
      after 7, 21, 42, and 84 days, respectively. Fracture healing and degradation
      pattern of the glue was studied using histological, histomorphometrical, scanning
      electron microscopical, and radiological methods. Good resorption of the glue by
      mononuclear and multinucleated giant cells without prolonged inflammatory
      processes was observed in the glue group. Histomorphometrical analysis did not
      reveal any significant differences in fracture healing between the glue and
      control group at any time. Complete remodelling of the former osteotomy gap was
      found in all rabbits after 84 days. This bioresorbable bone adhesive exhibited
      good biocompatibility and its degradation did not interfere with physiological
      fracture healing.

PMID- 15482827
TI  - Material-specific thrombin generation following contact between metal surfaces
      and whole blood.
AB  - Little is known about the blood compatibility of metals used in various medical
      devices. We have previously shown that titanium and derivatives thereof are among
      the most thrombogenic materials which may explain its outstanding
      osteointegrating properties. The aim of the present study was to characterize the
      thrombogenic and complement-activating properties of various metals used today in
      medical applications. Polyester chips were coated with 50- to 100-nm thick layers
      of aluminium, iridium, indium, nickel, tantalum, tin, titanium, or zirconium
      using magnetron sputtering. The metal-coated chips were then incubated in direct
      contact with whole blood in an in vitro chamber model, and the blood was then
      analyzed for platelet counts, thrombin-antithrombin (AT), fXIIa-AT, fXIa-AT and
      fXIIa-C1INH complexes and the complement parameters C3a and sC5b-9. Titanium,
      tantalum and indium were found to exhibit pronounced thrombogenic properties,
      whereas aluminium, nickel and, in particular, iridium were essentially non
      thrombogenic. Tin and zirconium were intermediate activators. All metals
      activated complement to a similar degree, with the exception of aluminium, which
      had more pronounced activating properties. This study clearly indicates that
      metals indeed have varying thrombogenic and complement activating properties.
      These studies have implications for the selection of metals intended for medical
      applications.

PMID- 15482828
TI  - Mechano-active tissue engineering of vascular smooth muscle using pulsatile
      perfusion bioreactors and elastic PLCL scaffolds.
AB  - Blood vessels are subjected in vivo to mechanical forces in a form of radial
      distention, encompassing cyclic mechanical strain due to the pulsatile nature of
      blood flow. Vascular smooth muscle (VSM) tissues engineered in vitro with a
      conventional tissue engineering technique may not be functional, because vascular
      smooth muscle cells (VSMCs) cultured in vitro typically revert from a contractile
      phenotype to a synthetic phenotype. In this study, we hypothesized that pulsatile
      strain and shear stress stimulate VSM tissue development and induce VSMCs to
      retain the differentiated phenotype in VSM engineering in vitro. To test the
      hypothesis, rabbit aortic smooth muscle cells (SMCs) were seeded onto rubber-like
      elastic, three-dimensional PLCL [poly(lactide-co-caprolactone), 50:50] scaffolds
      and subjected to pulsatile strain and shear stress by culturing them in pulsatile
      perfusion bioreactors for up to 8 weeks. As control experiments, VSMCs were
      cultured on PLCL scaffolds statically. The pulsatile strain and shear stress
      enhanced the VSMCs proliferation and collagen production. In addition, a
      significant cell alignment in a direction radial to the distending direction was
      observed in VSM tissues exposed to radial distention, which is similar to that of
      native VSM tissues in vivo, whereas VSMs in VSM tissues engineered in the static
      condition randomly aligned. Importantly, the expression of SM alpha-actin, a
      differentiated phenotype of SMCs, was upregulated by 2.5-fold in VSM tissues
      engineered under the mechano-active condition, compared to VSM tissues engineered
      in the static condition. This study demonstrates that tissue engineering of VSM
      tissues in vitro by using pulsatile perfusion bioreactors and elastic PLCL
      scaffolds leads to the enhancement of tissue development and the retention of
      differentiated cell phenotype.

PMID- 15482829
TI  - Formation of melanocyte spheroids on the chitosan-coated surface.
AB  - The search for biocompatible materials that can maintain function of melanocytes
      as the cellular patch is a feasible alternative for use in the autologous
      melanocyte transplantation for vitiligo. In this study, we demonstrated that the
      surface of chitosan-coated polystyrene wells supported the growth and phenotype
      expression of melanocytes. Depending on the seeding density and culture time,
      melanocytes were monolayered or spheroidal in morphology. At seeding densities
      above 10 x 10(3) cells/cm2, human melanocytes started to aggregate on the surface
      of chitosan after 2 days in culture. These aggregates grew into compact
      melanocyte spheroids on day 3 and more melanocyte spheroids were observed when a
      higher seeding density was used. Cells remained viable in the spheroids and grew
      into dendritic melanocytes when they were reinoculated on polystyrene wells.
      Conversely, the time for the formation of melanocyte spheroids needed a longer
      period at lower seeding density. For example, melanocytes at as low as 1.25 x
      10(3) cells/cm2 did not aggregate until the 20th day of culture. In order to
      interpret the phenomenon further, we proposed the formation of melanocyte
      spheroids on the chitosan is mediated by a balance between two competing forces:
      the interactions of cell-chitosan and cell-cell.

PMID- 15482830
TI  - Micropatterned polymer substrates control alignment of proliferating Schwann
      cells to direct neuronal regeneration.
AB  - Microcontact printed polymeric substrates were evaluated for their ability to
      control Schwann cell attachment and direct proliferation, as Schwann cell
      guidance is a crucial factor in directing peripheral nerve regeneration.
      Elastomeric stamps of poly(dimethylsiloxane) were "inked" with laminin, a
      permissive protein for Schwann cell adhesion, and stamped onto poly(methyl
      methacrylate) substrates to create patterns of lines and intervals varying from
      10 to 50 microm wide. Schwann cells were seeded onto the substrates in serum-free
      media. After 4h, media was replaced with serum-containing growth media and
      changed daily thereafter. The addition of growth media to stimulate proliferation
      initially caused some loss in cell orientation relative to the laminin pattern,
      but when monolayer formation was complete, a high degree of cell orientation was
      observed. As both cell-cell contacts and surface coverage were maximized, the
      Schwann cells achieved an even higher order of orientation than observed during
      the early stages of proliferation. Significantly, smaller pattern widths
      increased the degree of orientation, regardless of interval width. Our results
      indicate that patterned polymeric substrates may enhance peripheral nerve
      regeneration by creating a highly ordered Schwann cell matrix for guidance of
      neurons.

PMID- 15482831
TI  - Production and characterization of ECM powder: implications for tissue
      engineering applications.
AB  - Two methods to produce a particulate form of extracellular matrix (ECM) from
      porcine urinary bladder were investigated. One method to produce the powder
      involved snap freezing a lyophilized form of the material and then pulverizing it
      in a grinding mill. The second method was similar except that the ECM was
      saturated in a solution of NaCl prior to snap freezing to precipitate salt
      crystals within the matrix before grinding. Several methods were utilized to
      analyze the particle size distribution and ultrastructure including sonic
      sifting, laser diffraction, and scanning electron microscopy (SEM). The salt
      precipitation method yielded a more uniform distribution of particles with a
      smaller mean diameter (158 vs. 191 microm). SEM showed that the particles
      produced by grinding without salt precipitation were irregularly shaped, sheet
      like particles. ECM particles produced by the salt precipitation method were
      round and porous in appearance with many particles in the range of 1 microm which
      tended to agglomerate with the larger particles and with each other. We conclude
      that the production of a comminuted form of ECM is possible and that the
      uniformity of particle size and shape are dependent upon the manufacturing
      methodology.

PMID- 15482832
TI  - Hemocompatibility and anaphylatoxin formation of protein-immobilizing
      polyacrylonitrile hemodialysis membrane.
AB  - Plasma proteins were covalently immobilized onto polyacrylonitrile (PAN) membrane
      to evaluate the hemocompatibility and anaphylatoxin formation. This is used as a
      model to study the effect of protein-adsorption on the blood-contacting response
      of hemodializing membranes. The proteins used were either platelet-adhesion
      promoting collagen (COL) or platelet-adhesion-inhibiting human serum albumin
      (HSA). The microstructure and characterization of the protein-immobilizing PAN
      membranes were evaluated by Coomassie dye assay, atomic force microscopy, X-ray
      photoelectron spectroscopy and water contact angle measurement. PAN-HSA membrane
      improved not only hemocompatibility including less platelet adhesion, longer
      blood coagulation times, and higher thrombin inactivity level, but also induced
      lower complement activation. On the other hand, PAN-COL membrane exhibited blood
      incompatibility, although induced less increase of C3, C4 antigens of serum.
      Overall results of this study demonstrated that the immobilization of HSA onto
      the surface of PAN membrane would be beneficial to improve the hemocompatibility
      and to reduce the anaphylatoxin formation during hemodialysis.

PMID- 15482833
TI  - Localisation of osteogenic and osteoclastic cells in porous beta-tricalcium
      phosphate particles used for human maxillary sinus floor elevation.
AB  - We and others have shown earlier that porous beta-tricalcium phosphate (TCP)
      (Cerasorb) can be used in patients to augment the maxillary sinus floor prior to
      placement of oral dental implants. To better understand the transformation of TCP
      particles into bone tissue, we analyse here the appearance of cells with
      osteogenic or osteoclastic potential in relation to these particles. In biopsies
      taken at 6 months after sinus floor augmentation we observed bone growth into the
      TCP particles but also replacement by soft connective tissue. To identify
      possible osteoprogenitor cells in this tissue, histological sections were
      immunostained with an antibody to Runx2/Cbfa1, an essential and early
      transcription factor for osteoblast differentiation. The osteogenic potential of
      cells was further confirmed by immunostaining for bone sialoprotein (BSP) and
      osteopontin (OPN). Other sections were stained for Tartrate Resistant Acid
      Phosphatase (TRAP) activity to identify cells with osteoclastic capacity.
      Runx2/Cbfa1 positive connective tissue cells were found in abundance throughout
      and around the TCP particles, even at a distance of several millimetres from the
      maxillary bone surface. About 95% of the cells found within TCP particles stained
      positive for Runx2/Cbfa1. Fewer cells stained positive for BSP and OPN,
      suggesting more mature osteoblastic properties. Mono- and binucleate TRAP
      positive cells, but no multinucleate TRAP-positive osteoclasts, were found in the
      soft tissue infiltrating the TCP and at the surface of the TCP particles. Both
      the Runx2/Cbfa1 positive and the TRAP-positive cells decreased apically with
      increasing vertical distance from the maxillary bone surface. This data suggests
      that the TCP particles attract osteoprogenitor cells that migrate into the
      interconnecting micropores of the bone substitute material by 6 months. The lack
      of large multinucleate TRAP positive cells suggests that resorption of the TCP
      material by osteoclasts plays only a minor role in its replacement by bone.
      Chemical dissolution, possibly favoured by a high cell metabolism in the
      particles, seems the predominant cause of TCP degradation. The abundance of
      Runx2/Cbfa1 positive cells would indicate that with a greater time of healing
      there will be further bone deposition into these particles.

PMID- 15482834
TI  - Short-term ecological risks of depositing contaminated sediment on arable soil.
AB  - Sediments act as sinks of suspended material from surface water. Dredging of
      regional waters and subsequent disposal of the sediment on soil may lead to
      contamination of the soil, in some cases resulting in exceedance of soil quality
      standards. Soil quality standards are based on total concentrations. Total
      levels, however, do not always give an indication of adverse effects in soil
      ecosystems. Instead, truly bioavailable concentrations should be used as
      indicators. In this study we aim to test a set of suited indicators. We carried
      out partition and accumulation assays with metals and polycyclic aromatic
      hydrocarbons (PAHs) in soils and mixtures of soil and sediment, as well as a
      limited number of toxicity bioassays. We also investigated the rate of
      disappearance of PAHs from mixtures of sediments and soils. The experiments
      confirm that total levels indeed are not indicative of truly occurring toxic
      effects: mixing of highly contaminated sediments with soil hardly gave rise to
      either additional accumulation of metals and PAHs or excess toxicity. This
      indicates that the bioavailability of the metals and PAHs present in the sediment
      is limited. This general finding is confirmed by the low rate of disappearance of
      PAHs from the mixtures. It is concluded that inclusion of the aspects of
      bioavailability, mixture toxicity, and degradation, in the way described in this
      report, will solve the major limitations of the current methodology of
      classification of contaminated sediments.

PMID- 15482835
TI  - Decreased sperm count and sexual behavior in mosquitofish exposed to water from a
      pesticide-contaminated lake.
AB  - A number of reproductive abnormalities have been observed in wildlife living in
      Lake Apopka, Florida, USA. To test whether these abnormalities can be attributed
      to compounds in the water, we exposed male mosquitofish from Boulware Spring
      (Alachua County, Florida) to water from Lake Apopka and two reference sites,
      Orange Lake and Boulware Spring, for 1 month. Subsequently, sperm counts, sexual
      behavior, and sex hormones (testosterone and 17beta-estradiol) were measured. A
      lower sperm count and disrupted sexual behavior were found in fish exposed for 1
      month to water from Lake Apopka, compared to those at the reference sites.
      Furthermore, sexual behavior and whole-body testosterone concentrations were
      correlated, suggesting androgen influences on the behaviors examined. We
      hypothesize that the presence of contaminants with antiandrogenic and estrogenic
      action in the water from Lake Apopka are the likely cause of the observed
      decrease in sperm count and impaired sexual behavior.

PMID- 15482836
TI  - Diazinon-induced endocrine disruption in bluegill sunfish, Lepomis macrochirus.
AB  - An attempt to reveal endocrine disruption in bluegill fish (Lepomis macrochirus)
      upon exposure to diazinon was made. Fish blood serum was collected and estradiol
      levels were measured following times of exposure to 60 microg/L of diazinon.
      Samples were drawn from the fish during each exposure period of 24, 48, 72 and 96
      h and 1 and 2 weeks. The sample estradiol levels were compared to those of a
      control. Ovarian tissue was examined. As necrosis increased within the ovaries,
      estradiol blood serum levels altered from those of the control sample (101
      pg/mL). Histopathology within the follicles became apparent as exposure time to
      diazinon increased. The changes in the ovarian follicles can be correlated to the
      estradiol levels in the blood. Mean estradiol level for the control group was
      101.53 pg/mL. Estradiol levels from the trial groups varied from those of the
      control (24 h, undetectable; 48 h, 74.04 pg/mL; 72 h, 57.16 pg/mL; 96 h; 39.15
      pg/mL; 1 week, 66.50 pg/mL; 2 weeks, undetectable). It seems that the initial
      shock experienced by the fish after 24 h of exposure resulted in an undetectable
      level of estradiol. The level of estradiol initially ascended, but it began to
      decline and after 1 week of exposure it ascended a little and became undetectable
      after 2 weeks. Nevertheless, throughout the exposure period the level of
      estradiol was lower than normal. Severe damage to the mature oocytes may be the
      reason for undetectable levels of estradiol after 2 weeks of exposure.

PMID- 15482837
TI  - Increased toxicity to Ceriodaphnia dubia in mixtures of atrazine and diazinon at
      environmentally realistic concentrations.
AB  - The acute toxicity of diazinon in combination with atrazine concentrations of 5,
      10, 20, and 40 microg/L was evaluated using Ceriodaphnia dubia. Atrazine
      concentrations as low as 5 microg/L in combination with diazinon significantly
      increased toxicity to C. dubia compared to diazinon alone. Atrazine and diazinon
      residues within water samples collected from 65 subbasins throughout Denton,
      Texas, USA were used to assess the environmental relevance of pesticide
      concentrations. A geographical information system was used to examine the
      relationship between subbasin land uses and pesticide concentrations. Significant
      correlations were observed between in situ atrazine and diazinon concentrations
      and some subbasin land uses. Atrazine was significantly (P < 0.05) correlated to
      diazinon during some months. Of the 276 samples collected, 39% exceeded our
      experimentally derived diazinon LC(50) value, and 39% exceeded our minimum
      atrazine concentration of 5.0 microg/L. Results indicate the potential for
      increased toxicity from mixtures of compounds at environmentally realistic
      concentrations.

PMID- 15482838
TI  - Macroinvertebrate community structure in agricultural streams: impact of runoff
      related pesticide contamination.
AB  - This study aims to assess the runoff-related pesticide contamination, among other
      environmental factors, that contributes to differentiation in the
      macroinvertebrate communities inhabiting six streams in northern Germany
      (Braunschweig, Lower Saxony). A total of 91 macroinvertebrate taxa were sampled
      three times (April, May and June 2000) during the main period of pesticide
      application to cereals and sugar beets in the catchment. Thirteen environmental
      variables (e.g., nutrients, discharge, in-stream structure), including runoff
      related pesticide concentrations expressed as a sum parameter based on toxicity
      units (TU(SUM)), were analyzed using canonical correspondence analysis (CCA) and
      redundancy analysis. CCA based on species-level data and environmental variables
      explained 48% of the variance, with TU(SUM), stream width, percentage of detritus
      in the stream bed, and temperature being the most important variables. The
      sampling dates were of minor importance for the classification. The community
      composition in three streams exposed to maximum total pesticide levels between
      0.2 x and 0.01 x acute toxicity to Daphnia (48-h LC(50)) was clearly distinct
      from that at three control sites. Redundancy analysis using average values of the
      environmental variables and taxonomic orders explained 95% of the variance, with
      TU(SUM) being the only significant variable. The results show that the present
      pesticide levels affect the invertebrate community structure in the field.
      Furthermore, they underline the potential for effects in the field at pesticide
      concentrations greater than 0.01 x acute toxicity to Daphnia and are thus in
      agreement with the assumptions underlying the standards set by the European Union
      uniform principle.

PMID- 15482839
TI  - Quantitative changes in the digestive gland cells of the snail Helix aspersa
      after exposure to the fungicide copper oxychloride.
AB  - This study investigated the relationship between accumulated copper in the
      digestive gland of Helix aspersa, after exposure to the fungicide copper
      oxychloride, and quantitative changes in the digestive gland cells of this snail.
      Snails were exposed to 80 and 240 microg g(-1) copper oxychloride for 6 weeks.
      Histological sections of digestive glands were analyzed by means of computer
      assisted image analysis. Results indicate that copper is strongly accumulated in
      the digestive gland and that this organ is the main site of copper accumulation
      in the snail body. Also, as a result of copper accumulation in the digestive
      gland, measurable changes in epithelium cell height and area of this organ occur.
      In the case of cell height, these changes are dose-related. It is concluded that
      changes in digestive gland cells, as a result of copper oxychloride exposure, may
      possibly serve as biomarkers of exposure to this fungicide.

PMID- 15482840
TI  - Toxicity of cadmium and zinc mixtures to cercarial tail loss in Diplostomum
      spathaceum (Trematoda:Diplostomidae).
AB  - The effects of cadmium and zinc mixtures on tail loss of the free-living
      cercarial stage of the parasitic fluke Diplostomum spathaceum were investigated
      at concentrations ranging from 0.1 to 10,000 microg/L. Cercariae were exposed to
      metal mixtures of equal concentrations, metal mixtures of unequal concentrations,
      and a low-dose pretreatment followed by high-dose exposure mixtures. Under
      control conditions as the cercarial population aged tail loss occurred naturally
      a few hours before death, with an increasing tail loss over time associated with
      a decrease in cercarial survival. Under all mixture exposures the period of tail
      loss was prolonged compared to single-metal exposures. In most test solutions
      this was associated with a similar increase in survival of cercariae. Inhibition
      of tail loss occurred in low concentrations (0.1-100 microg/L) of equal mixed
      exposures. In some unequal, and in all pretreatment mixture exposures, a
      significant stimulation of tail loss occurred compared to the pattern of
      decreasing survival over time within the cercarial population. The importance of
      toxic metal mixtures to cercarial tail loss and potential implications for
      successful parasite transmission are discussed.

PMID- 15482841
TI  - Heavy metal contamination in little owl (Athene noctua) and common buzzard (Buteo
      buteo) from northern Italy.
AB  - In this study, two raptor species, the common buzzard (Buteo buteo) and the
      little owl (Athene noctua), were investigated for lead and cadmium
      concentrations, using liver, kidneys, pectoral muscle, sternum bone, and
      feathers. All the collected birds died at the Centro Recupero Rapaci of Lega
      Italiana Protezione Uccelli in Sala Baganza (Parma, Italy). They arrived alive at
      the Centro between November 1998 and November 1999 but died or were put to death
      as a consequence of injuries or other ailments. The results of the investigation
      do not show an excessive exposure to cadmium, whereas some interesting data have
      emerged in the case of lead. The concentration of the latter in the liver and in
      the bone of two little owls seem to suggest the possibility of chronic exposure.
      The high values found in one common buzzard, on the other hand, suggest an acute
      exposure and, probably, a case of lead shot ingestion.

PMID- 15482842
TI  - Age-specific immunocompetence of the earthworm Eisenia andrei: exposure to
      methylmercury chloride.
AB  - Little information with regard to the sensitivity of the immune system of
      earthworms to toxicants is currently available. To that effect, we evaluated the
      yield of coelomocyte immune cells and their phagocytosis potential for four
      different stages of development of the earthworm Eisenia andrei both for in vitro
      and in vivo exposure. Cell viability was similar among size classes; extruded
      cell yield increased from 0.7 x 10(6) cells/worm in the smallest size class to
      2.9 x 10(6) cells/worm in the largest size class. The proportion of
      phagocytically active cells was lower in the smallest groups but not different
      among the other three groups. Phagocytosis increased incrementally for the first
      three age/weight groups. The absolute phagocytosis level of the hatchling worms
      is significantly lower than that of the adult worms. The in vivo filter paper
      exposure of the mature worms showed a hormetic stimulation of 200-300% of
      phagocytosis and no significant effects on the phagocytosis potential of the
      hatchlings. The absolute response of coelomocytes from younger worms was
      significantly lower and the estimates of lethal mercury concentrations showed the
      hatchling worms to be roughly three times more sensitive than mature worms.

PMID- 15482843
TI  - Cyst-based toxicity tests XVII--prefeeding advantages in short-chronic rotifer
      microbiotests.
AB  - Attempts were made to overcome too-low reproductive output in the 48-h short
      chronic microbiotest with the rotifer Brachionus calyciflorus fed with microalgae
      (Pseudokirchneriella subcapitata) from algal beads older than 4 months
      (Chemosphere 50 (2002a) 365). Prefeeding of freshly hatched rotifers prior to the
      start of the actual growth experiments resulted in a satisfactory reproduction
      (i.e., an intrinsic growth rate r > 0.65), even with subsequent feeding of the
      rotifers with microalgae from beads stored up to 1 year. Rotirich is an
      attractive alternative inert food compared with the mixture of microalgae and
      Spirulina, originally used to prefeed the rotifers. When the rotifers were prefed
      for 2 h with 30 microg/mL Rotirich, it was then not necessary to add Spirulina to
      the microalgal food from beads. The above findings are a substantial
      simplification of the testing procedure of the new short-chronic
      "culture/maintenance-free" Rotoxkit microbiotest.

PMID- 15482844
TI  - Mesopodopsis slabberi (Crustacea: Mysidacea): can it be used in toxicity tests?
AB  - Mesopodopsis slabberi is a euryhaline and suprabenthic mysid with a wide
      geographic distribution and one of the most important mysid species in coastal
      shallow waters. Nevertheless, no references were found to its uses in
      ecotoxicological experiments (TOXNET, AQUIRE, ISI Web of Knowledge). This work is
      part of an ecotoxicological study, representing the first step in establishing a
      description of this species' tolerance to chemical pollutants typical of
      estuarine environments. It is possible to assert that acclimation was achieved,
      for it occurred during a period of time, with a low mortality. Due to the short
      life cycle of M. slabberi it is strongly believed that 12 days of acclimation is
      a far too long time, when experiments are to be made after this period. This
      species is suitable for acclimation in the laboratory, tolerant, and easy of
      handling. Logistics and materials used to maintain the acclimation system as
      described are simple and not costly and could easily be used in other
      laboratories.

PMID- 15482845
TI  - Assessment of anthracene toxicity toward environmental eukaryotic microorganisms:
      Tetrahymena pyriformis and selected micromycetes.
AB  - The toxicity of anthracene, a nonmutagenic, noncarcinogenic, low-molecular-weight
      polycyclic aromatic hydrocarbon present in the environment, was assessed using a
      ciliated protozoan, Tetrahymena pyriformis, and a selection of 10 micromycetes
      from different taxonomic groups living in two environmental compartments, namely
      aquatic and soil ecosystems. With T. pyriformis, a concentration-dependent
      inhibitory effect was shown on the cell proliferation rate, IC(50) = 33.40+/-4.84
      mg/L (kinetic method). Phagocytosis of nonsoluble anthracene was confirmed by the
      presence of digestive vacuoles with photon microscopy. In fungi, anthracene did
      not exhibit a fungicide effect but showed a fungistatic action. Except for
      Absidia fusca and Cladosporium herbarum, the micromycetes showed a concentration
      dependent decrease in growth. From IC(50) values determined by endpoint or
      kinetic methods, Rhodotorula glutinis and all of the Ascomycotina (except for
      Penicillium chrysogenum) were the most sensitive species, while Phanerochaete
      chrysosporium, P. chrysogenum, and the two Deuteromycotina were more resistant to
      anthracene. Our discussion focuses on the evaluation of toxicity by the two
      methods used for the calculation of the IC(50) values (endpoint and kinetic), the
      advantages of studying growth by a kinetic method (the dynamic aspect), and a
      comparison of toxicity to T. pyriformis and the different micromycetes.

PMID- 15482846
TI  - Peroxidation in muscle and liver tissues from fish in a contaminated river due to
      a petroleum refinery industry.
AB  - In this study, we aimed to investigate the possible effects of the wastewater
      water contamination of a petroleum industry on the oxidant/antioxidant status of
      muscle and liver tissues from fish in the Kizilirmak River, Kirikkale, Turkey.
      The antioxidant/oxidant parameters were analyzed in the muscle and liver tissues
      from fish in 10 km of the river above and below the industry. Malondialdehyde
      (MDA) and susceptibility to oxidation (SO) values were measured in the liver and
      muscle tissues as indexes of oxidation, and antioxidant potential (AOP),
      superoxide dismutase (SOD), glutathion peroxidase (GSH-Px), and catalase(CAT)
      activities were measured as indexes of antioxidant status. There was significant
      oxidation in the muscle tissue of the fish obtained in the river downstream of
      the industry compared to those obtained upstream of the industry. Although there
      were no meaningful differences between the SOD and GSH-Px activities, the AOP
      value and CAT activities were found to be reduced in the muscle tissues from the
      fish obtained downstream. In the liver tissues, the SOD and GSH-Px activities
      were found to be increased in the fish obtained downstream but no differences
      were observed in the MDA, SO, AOP, and CAT values. Our results suggest that some
      contaminants from the petrochemical industry cause oxidation in fish muscle
      tissues by impairing the antioxidant system. However, because no peroxidation was
      observed in the liver tissue from the downstream fish, it is possible that liver
      tissues have a stronger antioxidant capacity than muscle.

PMID- 15482847
TI  - Evaluation of sister chromatid exchange and chromosomal aberration frequencies in
      peripheral blood lymphocytes of gasoline station attendants.
AB  - Petroleum derivatives constitute a complex mixture of chemicals which contain
      well-known genotoxicants, such as benzene. Thus, chronic occupational exposure to
      such derivatives may be considered to possess genotoxic risk. In the present
      study, frequencies of sister chromatid exchange (SCE); aberrant cells, including
      numerical and structural chromosomal aberrations; and chromosome aberrations were
      investigated in peripheral blood lymphocytes from 30 exposed workers (15 smokers
      and 15 nonsmokers) and 30 controls (15 smokers and 15 nonsmokers). The exposed
      subjects were employed at 12 different petrol pumping stations in the city of
      Mersin, Turkey. Urinary phenol levels of exposed workers were found to be
      significantly higher than those of control subjects. Benzene exposure and
      cigarette smoking decrease the replication index and mitotic index. There is an
      interaction between benzene exposure and cigarette smoking for replication index
      and mitotic index. There is no interaction between cigarette smoking and benzene
      exposure for chromosomal aberrations. The results indicate that there are
      significant differences in SCE values in the exposed workers compared to the
      control individuals (P < 0.01), but there is no difference between smokers and
      nonsmokers for SCE frequency (P > 0.05). SCE frequency is higher in smokers than
      in nonsmokers.

PMID- 15482848
TI  - Altered B lymphocyte function induces systemic autoimmunity in systemic
      sclerosis.
AB  - Systemic sclerosis (SSc) is a connective tissue disease characterized by
      excessive extracellular matrix deposition in the skin and visceral organs. SSc is
      associated with immune activation characterized by autoantibody production,
      lymphocyte activation, and release of various cytokines. The presence of
      autoantibodies is a central feature of immune activation in SSc. Although
      autoantibodies are thought to be closely linked to the pathogenesis of SSc, the
      pathogenic relationship between systemic autoimmunity and the clinical
      manifestations of SSc, including skin fibrosis, remains unknown. Recent studies
      have revealed that B cells play a critical role in systemic autoimmunity and
      disease expression through various functions, including cytokine production in
      addition to autoantibody production. The B cell signaling thresholds are
      regulated by response regulators that augment or diminish B cell signals during
      responses to self and foreign antigens. Abnormal regulation of the response
      regulator function and expression may result in autoantibody production. Among
      these response regulators, CD19, which is a critical cell-surface signal
      transduction molecule of B cells, is the most potent positive regulator.
      Transgenic mice that overexpress CD19 by approximately 3-fold lose tolerance and
      generate autoantibodies spontaneously. B cells from SSc patients exhibit a 20%
      increase in CD19 expression that induces SSc-specific autoantibody production in
      transgenic mice. Furthermore, SSc patients have intrinsic B cell abnormalities
      characterized by expanded naive B cells, activated but diminished memory B cells,
      and chronic hyper-reactivity of memory B cells, possibly due to CD19
      overexpression. Similarly, B cells from a tight-skin mouse, a model of SSc, show
      augmented CD19 signaling and chronic hyper-reactivity. Remarkably, CD19 loss
      results in inhibition of chronic B cell hyper-reactivity and elimination of
      autoantibody production, which is associated with improvement in skin fibrosis
      and a parallel decrease in IL-6 production by B cells. Thus, chronic B cell
      activation resulting from augmented CD19 signaling leads to skin fibrosis
      possibly through IL-6 overproduction, as well as autoantibody production, in
      tight-skin mice and SSc patients.

PMID- 15482849
TI  - Dual reporter system to dissect cis- and trans-effects influencing the mutation
      rate in a hypermutating cell line.
AB  - Activation induced cytidine deaminase (AID) plays a key role in the induction of
      somatic hypermutation and class switching in the immunoglobulin genes of B
      lymphocytes. AID expression by itself is sufficient to induce a GC-basepair
      biased mutator phenotype in lymphoid and non-lymphoid cell lines. Nevertheless a
      network of cis-regulatory elements and additional trans-factor proteins seems to
      govern the molecular mechanism of somatic hypermutation. To address the nature of
      mutation rate changes observed in the hypermutating pre-B cell line 18-81, we
      extended our previously described green fluorescent protein (GFP) reversion
      system. Introducing an additional mutation reporter transgene enables us to
      discriminate between cis- and trans-factor caused alterations in the mutator
      phenotype. We show here that in cell line 18-81 the mutation rate declines upon
      prolonged periods of cell culture. The gradual loss of the mutator phenotype in
      cell line 18-81 is due to the downregulation of endogenous AID expression and can
      be reconstituted by overexpression of human AID protein. A correlation between
      AID mRNA levels and mutation rates is evident and even small changes in AID
      expression levels cause a significant effect on the mutability of the reporter
      transgenes.

PMID- 15482850
TI  - Identification of an Sp factor-dependent promoter in GCET, a gene expressed at
      high levels in germinal center B cells.
AB  - Antigen-stimulated B lymphocytes undergo genetic and phenotypic changes in
      germinal centers (GCs), including affinity maturation of immunoglobulin (Ig)
      genes and Ig heavy chain isotype switching. Expression of the Germinal Center
      Expressed Transcript (GCET) gene is up-regulated in murine GC B cells. The human
      homolog of GCET, HGAL/GCET2, is an important prognostic marker for staging
      lymphomas derived from GCs. To identify mechanisms that control cell type
      specific transcription of GCET, we localized promoter sequences using S1 nuclease
      protection and functional assays. Sequences comprising a TATA-less promoter were
      localized to a short region upstream of multiple mRNA start sites. In functional
      assays, the promoter is active in cells irrespectively of endogenous GCET gene
      expression. In vitro binding assays identified a non-consensus binding site for
      Sp factors near sites of transcriptional initiation. The site binds Spl and Sp3
      in nuclear extracts and recombinant Spl in vitro, and is required for full
      promoter function in transient promoter assays. Activation of the promoter by Spl
      or Sp3 in Spl/3-deficient cells was largely dependent on the Sp site. Together,
      these data provide the first analysis of regulatory modules necessary for GCET
      expression, a model for GC B cell-specific transcription.

PMID- 15482851
TI  - Differential allele expression of host defense genes, pulmonary surfactant
      protein-A and osteopontin, in rat.
AB  - Differential allele-specific expression has been observed in several genes
      involved in immunity. SP-A and OPN play a role in innate host defense. To
      determine whether SP-A and OPN are subject to differential allele-specific
      regulation, we investigated their gene or allele-specific expression in various
      tissues. The results showed: (1) Tissue-specific expression with high levels in
      lung (SP-A) and kidney (OPN). (2) Differences in allele-specific expression among
      individuals and tissues. SP-A showed an exclusively balanced biallelic expression
      (BB) in lung, but both BB and imbalanced biallelic (IB) expression in colon.
      Allele expression of OPN was more heterogeneous, e.g. in colon BB (22%), IB
      (64%), and monoallelic expression (MO) (14%). (3) Differential allele-specific
      expression was observed in all tissues studied (OPN) or in all extrapulmonary
      tissues (SP-A). (4) Family studies indicated that inheritable factor(s) may be
      involved in the regulation of allele-specific expression. (5) Analysis of co
      expression of gene-specific alleles from double heterozygous rats revealed lack
      of coordinate allele expression among SP-A, SP-D, and OPN. We conclude that
      allele-specific expression occurs among genes of innate host defense. This may
      yet provide another level of regulatory complexity for molecules involved in the
      first line of defense.

PMID- 15482852
TI  - Up-regulation of CD80-CD86 and IgA on mouse peritoneal B-1 cells by porin of
      Shigella dysenteriae is Toll-like receptors 2 and 6 dependent.
AB  - Porin of Shigella dysenteriae type 1 increased the mRNA levels for Toll-like
      receptor (TLR) 2 and TLR6 by 1.5- and 2.9-fold respectively, of peritoneal cavity
      B-1a and B-1b cells, implicating that coexpression of TLR2 and TLR6 is essential
      as a combinatorial repertoire for recognition of porin by the B-1 cells. Among
      the two key TLRs, TLR2 and TLR4, which are primarily responsible for recognizing
      majority of the bacterial products, TLR2 and not TLR4, participates in porin
      recognition. TLR2 got increased on both the B-1 cell populations whereas the TLR4
      expression remained unaffected. Besides TLRs, mRNA for MyD88, an effector
      molecule associated with TLR-mediated response was enhanced by 1.8-fold that
      suggests of its involvement in the activity of porin. Both of the B-1 cell
      populations expressed strongly the mRNA for NF-kappaB in the presence of porin,
      that was 2.4-fold more than untreated control, conforming to the earlier finding
      that coexpression of TLR2 and TLR6, resulted in robust NF-kappaB activation for
      signaling. Porin treatment of B-1 cell populations of C57BL/6 mice, and C3H/HeJ
      mice in particular, selectively up-regulated the expression of the costimulatory
      molecules. CD80 expression got enhanced on the B-1a cells whereas CD86 got solely
      expressed on B-1b cells. Porin-induced cell surface expression of IgM and IgA on
      B-1 cell populations from C57BL/6 mice. The IgA-generating capacity, hallmark of
      mucosal immune response, was confirmed with B-1 cells of C3H/HeJ, the
      lipopolysaccharide non-responder mouse, in response to the protein. The porin
      mediated induction of IgA was augmented by interleukin-6 on B-1a and B-1b cells,
      by 2.4- and 2.6-fold, respectively. The IgA expressed on both B-1a and B-1b cell
      surfaces after 72 h of culture was found to bind to the 38 kDa monomer of porin
      confirming it to be anti-porin IgA antibody.

PMID- 15482853
TI  - Structural implication of the induced immune response by Bacillus thuringiensis
      Cry proteins: role of the N-terminal region.
AB  - The potential role of the regions (carboxil and amino) of the Cry proteins in the
      ability of these proteins to elicit strong immune responses was investigated.
      Intraperitoneal immunization of mice with the homologous Cry1A protoxins (130-133
      kDa), with the long C-terminal half gave rise mostly to similar, strong serum and
      mucosal IgG and IgM antibody response but a lower induction of these Ab by
      intranasal route. Remarkably, Cry3A protoxin, devoid of C-terminal half was able
      to induce a significant mucosal IgG, and IgM Ab as well as Cry1A protoxins,
      suggesting us that immunogenic abilities are not restricted to C-terminal half
      but N-terminal half itself could be involved. In fact, this assumption was
      strengthen by the strong immunogenic abilities of the Cry1A toxins, specially IgG
      and IgA Ab induced by both routes in different mucosal sites. These data indicate
      that immunogenic abilities of the Bt Cry proteins reside and depends of the N
      terminal half.

PMID- 15482854
TI  - Autoimmune regulator induced changes in the gene expression profile of human
      monocyte-dendritic cell-lineage.
AB  - The autoimmune regulator (AIRE) is a transcriptional regulator expressed in the
      thymic medullary epithelial cells and in the cells of the monocyte-dendritic
      lineage both in the thymus and in the secondary lymphoid organs. Mutations in the
      AIRE gene cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy
      (APECED), a recessively inherited disease characterized by loss of immunological
      self-tolerance to multiple endocrine organs. Recent mouse knockout studies
      suggest that AIRE is responsible for ectopic expression of peripheral self
      antigens in the thymus. In the present study, we detected an increased level of
      endogenous AIRE expression during the differentiation process of the human
      monocyte derived dendritic cells (MoDCs). We subsequently identified candidates
      for AIRE-regulated genes by using cDNA microarray technology to analyse the
      changes in the gene expression profile brought about by overexpressing the AIRE
      protein in the monocytic U937 cells. The changes observed resembled those
      previously reported to occur during the maturation of DCs, including up
      regulation of the CCL22, CD25, ICAM-1 and RelB genes. In contrast, increased
      expression of the steroidogenic enzymes P450c17, P450c21 and P450scc, the major
      autoantigens in APECED, was not found either in our cell model or in the
      dendritic cell cultures. We also identified the ERK signal transduction pathway
      as a candidate for mediating the signal that results in the altered expression
      profile. Our findings suggest that the role of AIRE in the DCs differs from its
      function in the thymus.

PMID- 15482855
TI  - Analysis of genes isolated from lipopolysaccharide-stimulated rainbow trout
      (Oncorhynchus mykiss) macrophages.
AB  - A primary cell culture system was used to obtain differentiated rainbow trout
      (Oncorhynchus mykiss) macrophages that were stimulated with Escherichia coli
      lipopolysaccharide (LPS-10 microg/ml) for 12 h in vitro. Messenger RNA from the
      LPS-stimulated cells was used to create two cDNA libraries from which a total of
      1048 sequences were analyzed. A large number of cDNAs were obtained that could be
      related to immune function including structural proteins, proteases and
      antiproteases, regulators of transcription and translation, cell death
      regulators, receptors, lectins and immunoglobulins, cytokines and chemokines,
      cell surface antigens, signal transduction proteins, antimicrobial peptides, and
      enzymes involved in eicosanoid synthesis. Selected genes that were analyzed by RT
      PCR and real time PCR and found to be upregulated by LPS, included vascular cell
      adhesion molecule, the CCAAT/enhancer binding protein beta, the inhibitor of NF
      kB alpha, CD209, a major histocompatibility class II-invariant chain protein,
      cyclin L1, acute phase serum amyloid A, and prostaglandin endoperoxide synthase
      2.

PMID- 15482856
TI  - Temperature-dependent isologous Fab-Fab interaction that mediates
      cryocrystallization of a monoclonal immunoglobulin G.
AB  - Mechanisms of the cryoprecipitation of cryoglobulins have long been studied but
      not fully understood. In the present study, we characterize a monoclonal
      immunoglobulin G1 (IgG1) cryoglobulin that forms sharp needle crystals upon
      cooling and therefore might be an ideal example for the elucidation of a
      mechanism of cryoprecipitation of cryoglobulins. Limited proteolysis by papain of
      this cryoglobulin resulted in disappearance of cryocrystallization. Interactions
      of the proteolytic fragments were examined by surface plasmon resonance
      measurements. A temperature-dependent isologous Fab-Fab interaction was observed
      for this cryoglobulin. Glycosylation profiling by use of the HPLC mapping
      technique revealed that cryoglobulin expresses homogeneous N-glycans in its Fc
      portion. These results suggest that (1) the temperature-dependent crystallization
      of the cryoglobulin was ascribed to its specific Fab-Fab interaction and (2) the
      unusual homogeneity of the Fc glycosylation promote the crystallization of this
      cryoglobulin.

PMID- 15482857
TI  - De-novo design of complementary (antisense) peptide mini-receptor inhibitor of
      interleukin 18 (IL-18).
AB  - Complementary (antisense) peptide mini-receptor inhibitors are complementary
      peptides designed to be receptor-surrogates that act by binding to selected
      surface features of biologically important proteins thereby inhibiting protein
      cognate receptor interactions and subsequent biological effects. Previously, we
      described a complementary peptide mini-receptor inhibitor of interleukin-1beta
      (IL-1beta) that was designed to bind to an external surface loop (beta-bulge) of
      IL-1beta (Boraschi loop) clearly identified in the X-ray crystal structure of
      this cytokine. Here, we report the de-novo design and rational development of a
      complementary peptide mini-receptor inhibitor of cytokine interleukin-18 (IL-18),
      a protein for which there is no known X-ray crystal structure. Using sequence
      homology comparisons with IL-1beta, putative IL-18 surface loops are identified
      and used as a starting point for design, including a loop region 1 thought to be
      equivalent with the Boraschi loop of IL-1beta. Only loop region 1 complementary
      peptides are found to be promising leads as mini-receptor inhibitors of IL-18 but
      these are prevented from being properly successful owing to solubility problems.
      The application of "M-I pair mutagenesis" and inclusion of a C-terminal arginine
      residue are then sufficient to solve this problem and convert one lead peptide
      into a functional complementary peptide mini-receptor inhibitor of IL-18. This
      suggests that the biophysical and biological properties of complementary peptides
      can be improved in a rational and logical manner where appropriate, further
      strengthening the potential importance of complementary peptides as inhibitors of
      protein-protein interactions, even when X-ray crystal structural information is
      not readily available.

PMID- 15482858
TI  - T cell recognition pattern of bovine milk alphaS1-casein and its peptides.
AB  - T cell recognition patterns of CAS1_Bovin, its limited hydrolysis, oxidized,
      reduced/alkylated, cyanogen bromide cleavage fractions and synthetic peptides
      were examined. Thirteen overlapping peptides covering the intact molecule, with
      chain lengths varied between 17 and 20 AA, were prepared by f-moc SPPS. In
      addition, six CNBr-cleavage fragments were obtained and extensively purified
      using RP/HPLC. Likewise, chemically modified derivatives and limited pepsin
      hydrolysate, were performed and the specificities were confirmed. Stimulation of
      PBMC and TCL cultures by the intact CAS1_Bovin molecule, synthetic peptides and
      modified derivatives were screened by [methyl-3H] thymidine incorporations. PBMC
      phenotype was performed by flow cytometry and the mean CD4+/CD8+ ratio of freshly
      prepared PBMC was compared with the ratio following specific CAS1_Bovin
      stimulation. CD4+ phenotypes (TH1/, TH2 and TH0) were assigned by assay of four
      marker cytokines IL-4, IL-6, IL-10 and IFN-gamma. Five CNBr fragments and seven
      of the thirteen tested peptides were recognized by specific TCL. The most
      reactive epitopes of CAS1_Bovin comprised seven motifs namely: peptides Cas 1-18,
      Cas 16-35, Cas 67-85, Cas 91-110, Cas 136-155, Cas 152-169 and Cas 166-183. The
      stimulation range for the seven peptides was 1058-2383 cpm. Stimulation for the
      CNBr fragments were, respectively, 8670, 5808, 3324, 5465, 2255 and 321 cpm.
      Cytokine assay showed that CD4+ TH2 phenotype was dominant for half the number of
      patients, while TH1 solely or combined TH0 were represented in the other four
      cell culture filtrates. The T cell reactive epitopes described and their
      antibodies will be useful tools for methods in progress for the detection of
      masked casein epitopes encompassed in processed food. In conclusion, T cell
      recognition pattern of CAS1_Bovin was examined using extensively purified
      synthetic peptides and CNBr fragments. Five large and seven small peptides were
      clearly recognized. Peptides of chain length less than six AA were left
      unrecognised. CD4+ TH2 phenotype was the most dominant TCL subpopulations found
      in atopic patients while CD4+ TH1 was representative in the non-IgE mediated type
      IV hypersensitivity.

PMID- 15482859
TI  - Genomic organization of peanut allergen gene, Ara h 3.
AB  - Type 1 hypersensitivity to peanut proteins is a well-recognized health problem.
      Several peanut seed storage proteins have been identified as allergens. Ara h 3,
      a glycinin protein, is one of the important peanut allergens. Although amino acid
      and cDNA sequences are available for Ara h 3, there is not information at the
      genomic level. The objectives of this study were to isolate, sequence, and
      characterize the genomic clone of peanut allergen, Ara h 3. A peanut genomic
      library was screened, using two [32P] end-labeled oligonucleotide probes designed
      based on cDNA sequences of Ara h 3 and Ara h 4. Four positives lambda FIX II
      clones were obtained after four rounds of screenings. Digestion with Sac I
      resulted in two fragments of 1.5 and 10 kb hybridizing to the probes. Both
      fragments were subcloned into p-Bluescript vector and sequenced. The Ara h 3 gene
      spans 3.5 kb and consists of four exons, three introns, 5' and 3' flanking
      regions. The open reading frame is 2008 bp long and can encode a polypeptide of
      538 amino acids residues. Sequences analogous to a TATA-box (TATAAAT), CAAT-box
      (AGGA), G-box (TCCTACGTGTCC) and several cis-elements were found in the promoter
      region. In the 3' downstream region, three polyadenylation signals (AATAAA) were
      identified.

PMID- 15482860
TI  - Histone acetyltransferase activity of p300 enhances the activation of IL-12 p40
      promoter.
AB  - Interleukin-12 (IL-12) is a heterodimeric cytokine produced by macrophages in
      response to intracellular pathogens and provides an obligatory signal for the
      differentiation of T-helper-1 cells. p300 is an important histone
      acetyltransferase (HAT) and has been implicated in the regulation of gene
      expression. Whether p300 plays a role in the IL-12 expression has not been
      investigated before. In this study, we analyzed the roles of p300 in the
      regulation of human IL-12 p40. By using RT-PCR and a series of co-transfection
      studies, we found that p300 had a stimulating effect on the expression of
      endogenous IL-12 p40 mRNA and on the activity of IL-12 p40 promoter. We also
      showed that the HAT activity of p300 was essential to its function in regulating
      IL-12 promoter, since the mutant p300 with the HAT domain deleted did not have
      such a stimulation effect. In addition, the adenovirus E1A protein suppressed the
      p300 function, whereas the mutant E1A lacking the p300 interaction domain did
      not. Furthermore, p300 was able to reinforce the c-Rel-mediated activation of IL
      12 p40. Results presented in this paper implicate that p300 is involved in the
      transcriptional regulation of IL-12 p40, and IL-12 p40 is one of the target genes
      of p300.

PMID- 15482861
TI  - Atomic force bio-analytics of polymerization and aggregation of phycoerythrin
      conjugated immunoglobulin G molecules.
AB  - While bio-labeled immunoglobulin (IgG) or antibodies are extensively used in
      imaging studies and therapeutic modality, there have been no reports describing
      atomic force microscopy (AFM) micrographs of these labeled IgG molecules. Here,
      AFM studies of phycoerythrin (PE)-conjugated IgG were undertaken to examine
      whether PE conjugation induced conformational changes or molecular interaction,
      and subsequently resulted in an alteration in nano-structures of PE-conjugated
      IgG complex. Once immobilized on mica, single PE-conjugated IgG molecule
      exhibited globular shape with approximately 60 microns in diameter and 5 microns
      in height. PE-conjugated IgG were able to form monomers, spindle-like trimers,
      and hexamers that developed through an end-end connection of two trimers, after
      they were continuously immobilized on mica. Interestingly, these multimers could
      aggregate in different directions to form circular monolayers with a highly dense
      core of PE-conjugated IgG polymers. The formation of these well-organized
      polymers and aggregates of PE-conjugated IgG may be attributed to the PE
      conjugation as well as the air-liquid tension on subtract. These findings may
      help to understand the nano-structures of bio-labeled IgG or antibodies, and
      facilitate the potential use of PE-conjugated antibodies as markers or
      immunosensers for AFM bio-analytics of biomolecules in cells and membranes.

PMID- 15482862
TI  - A meta-analytic investigation of the relationship between the psychological
      distress of cancer patients and their carers.
AB  - The identification of factors that might affect the relationship between
      patients' and carers' psychological distress has received insufficient attention
      to date. A meta-analysis was conducted with 21 independent samples of cancer
      patients and their carers, to quantify the relationship and difference between
      respective measures of psychological distress. Correlation coefficients and
      standard differences were extracted from 21 studies that met pre-defined
      inclusion criteria. Random effects models were used. Variables that modified this
      relationship were examined with potential causes of heterogeneity explored.
      Analysis confirmed the positive association between patient and carer
      psychological distress (r = 0.35, P<0.0001), and indicated that patients and
      carers did not experience significantly more or less psychological distress than
      one another (P = 0.64). Subgroup analysis was performed to explore potential
      sources of heterogeneity, and initial findings indicated a relationship between
      time since diagnosis and the strength of correlation between patient and carer
      psychological distress. The meta-analysis was limited by the large clinical and
      methodological variability between studies, and further systematic prospective
      research is required. This preliminary evidence suggests that early intervention
      with the patient and their carer could prevent later development of psychological
      distress in both members.

PMID- 15482863
TI  - Chronic illness and depressive symptoms in late life.
AB  - The relationship between illness and depressive symptoms is examined using a
      large, nationally representative, and longitudinal sample of Americans over the
      age of 50. Seven illnesses (cancer, stroke, heart condition, chronic obstructed
      pulmonary disease, diabetes, high blood pressure, and arthritis) and three forms
      of disability (activities in daily living, mobility, and strength) substantially
      increase symptoms. Yet, most of these positive effects diminish with age.
      Multiplicative interactions between age and illness indicate that those who
      develop chronic illnesses earlier in life tend to report more depressive symptoms
      than do those who develop them later. Similarly, disability leads to more
      depressive symptoms when experienced at younger ages. This age-graded effect
      emerges even for illnesses that are known to share a biological substrate with
      depression (e.g. vascular disorders). The results are discussed with respect to
      theories of illness, depression, and aging.

PMID- 15482864
TI  - Impact of depression on disablement in late middle aged and older persons:
      results from the Longitudinal Aging Study Amsterdam.
AB  - The main pathway of the disablement process consists of four consecutive phases:
      Pathology (presence of disease/injury), Impairments (dysfunctions/structural
      abnormalities), Functional Limitations (restrictions in basic physical/mental
      actions), and Disability (difficulty doing activities of daily life, ADL). This
      study determines the presence of the main pathway of disablement in a cohort aged
      55 years and older and examines whether progression of the main pathway of
      disablement is accelerated in the presence of depression. Based on baseline (T1)
      and two three-year follow-up interviews (T2 and T3) from the Longitudinal Aging
      Study Amsterdam (LASA) in a population-based cohort of 1110 Dutch persons, we
      first analysed the intermediate effect of the different consecutive phases of the
      disablement process by means of multiple regression, adjusted for covariates.
      Then, depression was used as interaction term in multiple regression analyses
      linking the consecutive phases of the disablement process. We found that
      Impairments mediated the association between Pathology and Functional
      Limitations, and that Functional Limitations mediated the association between
      Impairments and Disability. Depression significantly modified the associations
      between Pathology and subsequent Impairments, and between Functional Limitations
      and subsequent Disability. In sum, the main pathway of the disablement process
      was identified in our sample. In addition, we found an accelerating effect of
      depression, particularly in the early and late stages of the model. Reduction of
      depression may help slow down the process of disablement for persons who find
      themselves in those stages of the model.

PMID- 15482865
TI  - 'Normal disruption': South Asian and African/Caribbean relatives caring for an
      older family member in the UK.
AB  - Little has been written on informal care of an older relative among minority
      ethnic groups in the UK. This paper examines the meanings of being an informal
      carer of an older family member for South Asian and African/Caribbean carers. The
      analysis presented here is based on qualitative interviews with 21
      African/Caribbean and 15 South Asian carers. Drawing primarily on the notions of
      biographical continuity, biographical reinforcement and biographical disruption,
      the meanings of caring are examined. The findings indicate that the experience of
      informal care has many similarities to the experience of chronic illness. Carers
      generally described the experience of caring as an accepted part of their
      biography, talking about their caring relationship in terms of their pre-caring
      and a continuation of their previous relationship with the person being cared for
      and their roles within the family. However, the participants also described
      highly disruptive elements to this change in the relationships. The paper
      attempts to consider the relationship between individual experiences, cultural
      factors and macro-social structures.

PMID- 15482866
TI  - Women's status and depressive symptoms: a multilevel analysis.
AB  - The effects of state-level women's status and autonomy on individual-level
      women's depressive symptoms were examined. We conducted a multi-level analysis of
      the 1991 longitudinal follow up of the 1988 National Maternal Infant Health
      Survey (NMIHS), with 7789 women nested within the fifty American states. State
      level women's status was assessed by four composite indices measuring women's
      political participation, economic autonomy, employment & earnings, and
      reproductive rights. The main outcome measure was symptoms of depression (Center
      for Epidemiologic Studies Depression Scale, CES-D). The participants were a
      nationally representative stratified random sample of women in the USA aged
      between 17 and 40 years old who gave birth to live babies in 1988, were
      successfully contacted again in 1991 and provided complete information on
      depressive symptoms. Women who were younger, non-white, not currently married,
      less educated or had lower household income tended to report higher levels of
      depressive symptoms. Compared with states ranking low on the employment &
      earnings index, women residing in states that were high on the same index scored
      0.85 points lower on the CES-D (p<0.01). Women who lived in states that were high
      on the economic autonomy index scored 0.83 points lower in depressive symptoms
      (p<0.01), compared with women who lived in states low on the same index. Finally,
      women who resided in states with high reproductive rights scored 0.62 points
      lower on the CES-D (p<0.05) compared with women who lived in states with lower
      reproductive rights. Gender inequality appears to contribute to depressive
      symptoms in women.

PMID- 15482867
TI  - Geographies of inequality: child pedestrian injury and walking school buses in
      Auckland, New Zealand.
AB  - In the face of mounting concern at traffic congestion in the vicinity of schools
      and the associated risks of child pedestrian injury, the 'walking school bus'
      (WSB) idea has been rapidly adopted within metropolitan Auckland. WSBs involve
      volunteers guiding children to and from school in an orderly manner following
      established walking routes. This paper reports on a survey of the 34 Auckland
      primary schools which had adopted the scheme by November 2002. Despite rates of
      child pedestrian injury being highest in areas of socio-economic deprivation, our
      survey found WSB developments highly concentrated in low deprivation
      neighbourhoods. The inequitable socio-spatial distribution of WSBs in Auckland
      suggests that the ability to respond to road safety issues is closely correlated
      with socio-economic privilege. While our respondents identified a number of
      individual and community health benefits accruing from WSBs, we conclude that the
      initiative has a limited ability to address public health challenges originating
      within an inequitable and car-dominated urban political system.

PMID- 15482868
TI  - Neighbourhood life and social capital: the implications for health.
AB  - Social capital has been linked to health outcomes, though there are some
      inconsistencies in the research and the link is dependent on the measures of
      social capital and health used. In this paper, we argue that social capital is
      multifaceted and its relationship with health is complex. We explore the
      relationship between a number of elements of neighbourhood life and neighbourhood
      based social capital, and health, using both qualitative and quantitative
      methods. The paper reports on a study of the Western suburbs of Adelaide and the
      analysis of 2400 questionnaires and 40 in-depth interviews. A partial least
      square path analysis was undertaken with the questionnaire data. It considered
      the impact of perceptions of the physical environment, neighbourhood connections,
      neighbourhood trust, reciprocity, perceived safety and local civic action, and a
      number of demographic variables, on physical and mental health as measured by the
      SF-12. Of the neighbourhood-related variables, only perceived neighbourhood
      safety was related to physical health, with neighbourhood safety and
      neighbourhood connections related to mental health. Of the demographic variables,
      higher-income level and educational achievement were related to better physical
      and mental health. In addition, physical health was lower and mental health
      higher within older age groups. The inter-relationships between the neighbourhood
      variables and demographic differences in experience of neighbourhood were also
      examined. The thematic analysis of the interviews linked a number of social
      aspects of neighbourhood, the physical neighbourhood environment, perceptions of
      safety, civic activities and availability of local services, to health outcomes.
      The paper concludes that there is a need for more complex measures of social
      capital and that socio-economic factors are of relatively greater importance in
      determining health.

PMID- 15482869
TI  - Types of provincial structure and population health.
AB  - This paper explores the potential of using large administrative units for studies
      of population health within a country. The objective is to illustrate a new way
      of defining structural dimensions and to use them in examining variation in life
      expectancy rates. We use data from the 50 provinces of Spain as a case study. A
      factor analysis of organizational items such as schools, hotels and medical
      personnel is employed to define and generate "collective" measures for well-known
      provincial types, in this case: urban, commercial, industrial and tourist
      provinces. The scores derived from the factor analysis are then used in a
      regression model to predict life expectancy. The City-centered and Commercial
      provinces showed positive correlations with life expectancy while those for the
      Tourist provinces were negative. The industrial type was nonsignificant.
      Explanations of these correlations are proposed and the advantages and
      disadvantages of this exploratory technique are reviewed. The use of this
      technique for generating an overview of social organization and population health
      is discussed.

PMID- 15482870
TI  - Cross-national variation in family influences on child health.
AB  - Drawing on the family process literature, child health models, and recent studies
      of macro-level effects on health, we examine the effects of household structure,
      resources, care-giving, reproduction, and communication on child nutritional
      status and infant mortality. Using Demographic and Health Surveys, we analyze the
      influence of these factors across 42 countries in Latin America, Africa, and
      Asia. We also consider country-level including nontraditional family structure,
      level of economic development and expenditures on health care. Our results
      underscore the importance of family resources, decision-making, and health and
      feeding practices on child well-being in less developed countries. Although there
      is cross-national variability, the size of the variability was small relative to
      the overall effect. The country-level measures had modest effects on infant
      mortality and child nutritional status.

PMID- 15482871
TI  - Implications of genetic risk information in families with a high density of
      bipolar disorder: an exploratory study.
AB  - While major susceptibility genes for bipolar disorder are yet to be identified,
      the opportunity exists to systematically ascertain the important issues and
      societal implications of genetic risk determination for bipolar disorder prior to
      these technological advances becoming widely available. This study explores, in a
      sample of families with a high density of bipolar disorder: (i) attitudes to
      predictive genetic and prenatal testing, using different risk frames; (ii)
      attributions for bipolar disorder, in particular the degree to which a genetic
      model is endorsed; and (iii) the impact of these attributions on the perceived
      stigma of bipolar disorder. A qualitative methodology was selected as most
      appropriate as no previous research has examined this issue. Participants were
      ascertained through a molecular genetics study of bipolar disorder. In-depth
      interviews were conducted with 21 members of families with a high density of
      bipolar disorder. Most participants reported being interested in genetic testing
      if it gave a definitive answer, while expressed interest in testing was lower if
      it gave a probable answer only. Almost all stressed that a genetic susceptibility
      and environmental factors interacted. Most participants felt that a genetic
      explanation was likely to decrease the stigma associated with bipolar disorder as
      it shifted the locus of control and responsibility away from the individual
      towards the role of heredity. Findings indicate that expressed interest in
      genetic testing depends on the certainty imparted by the test. Results suggest
      that families with bipolar disorder are likely to benefit psychologically from
      information about the genetic basis of bipolar disorder.

PMID- 15482872
TI  - Changing organisations: a study of the context and processes of mergers of health
      care providers in England.
AB  - This paper presents findings from a study of the context and processes of
      provider mergers in the NHS in England. Mergers are an example of organisational
      restructuring, a key lever for change in the UK health care sector and elsewhere,
      although it is only one strategy for organisational change. The framework for the
      study is key themes from the organisational change literature: the complexity of
      the effects of change; the importance of context; and the role of organisational
      culture. The drivers for health care mergers and the evidence for these are
      analysed. Using documentary analysis and in-depth qualitative interviews with
      internal and external stakeholders, the first part of the paper reports on stated
      and unstated drivers in nine mergers. This provides the context for four in-depth
      case studies of the process of merger in the second and third years post-merger.
      Our study shows that the contexts of mergers, including drivers of change, are
      important. Merger is a process without clear boundaries, and this study shows
      problems persisting into the third year post-merger. Loss of management control
      and focus led to delays in service developments. Difficulties in the merger
      process included perceived differences in organisational culture and perceptions
      of 'takeover' which limited sharing of 'good practice' across newly merged
      organisations. Merger policy was based on simplistic assumptions about processes
      of organisational change that do not take into account the dynamic relationship
      between the organisation and its context and between the organisation and
      individuals within it. Understanding the process of merger better should lead to
      a more cautious approach to the likely gains, provide understanding of the
      problems that are likely in the period of change, and anticipate and avoid
      harmful consequences.

PMID- 15482873
TI  - Effectiveness of a multi-component intervention on dispensing practices at
      private pharmacies in Vietnam and Thailand--a randomized controlled trial.
AB  - Private pharmacies are the first line of health care in many communities,
      commonly selling antibiotics in small doses and prescription-only drugs such as
      steroids without medical supervision. The aim was to study the effectiveness of a
      multi-faceted intervention on the dispensing practices of drug sellers in Hanoi
      and Bangkok. The study was a randomized, controlled trial with 68 Hanoi and 78
      Bangkok pharmacies, randomly selected and assigned for intervention and control.
      Behaviour was assessed by five simulated client visits per pharmacy per
      dispensing practice, at baseline and a month or more after each intervention.
      Three three-month interventions were implemented sequentially with four months in
      between: enforcement of regulations with local inspectors visiting to emphasize
      the importance of prescription-only medicine legislation; education, performed
      face-to-face in Hanoi and by a large group in Bangkok; and peer review, voluntary
      in Bangkok and compulsory in Hanoi. The intervention resulted in significant
      improvements in Hanoi, reducing the dispensing of illegal steroids (29% vs. 62%)
      and low dose antibiotics (69% vs. 90%), sustained by means of the peer review
      (17% vs. 57% steroids and 71% vs. 95% antibiotics), and in fewer dispensers
      asking no questions and giving no advice (11% vs. 30% steroids and 51% vs. 81%
      antibiotics). The only significant improvement in Bangkok was the reduction in
      illegally dispensing steroids (25% vs. 44%) after the regulatory intervention. In
      Bangkok, fewer of those in the group who volunteered for the peer review asked no
      questions and gave no advice for low-dose antibiotics requests after the peer
      review (58% vs. 81%). A multi-component intervention can have a profound effect
      in changing dispensers' behaviour, but the effect is dependant on the context and
      the method of implementation. Possible reasons for differences are discussed.

PMID- 15482874
TI  - Diffusion of breast conserving surgery in medical communities.
AB  - Excluding skin cancers, breast cancer is the most common form of cancer in women.
      Due to an increased focus on early detection, many more cases of breast cancer
      are now diagnosed at an early stage, which makes the use of breast conserving
      surgery (BCS) an efficacious and often more desirable treatment choice than
      mastectomy. An analysis of the variation in the use of BCS in the United States
      was performed using data from the years 1988 and 1994, and stratifying hospitals
      on the basis of teaching status. In both 1988 and 1994, BCS was highest in
      academic teaching hospitals and lowest in community hospitals. This finding is
      interpreted within the framework of classical diffusion theory. Social and
      cultural norms in local medical communities have a strong effect on the degree to
      which innovations diffuse rapidly or not. This analysis is useful in the
      understanding of geographic and hospital-based variations in treatment for early
      stage breast cancer and other illnesses that have long and strongly held
      traditions of treatment.

PMID- 15482875
TI  - A naturalistic inquiry on the impact of interventions aiming to improve health
      and the quality of life in the community.
AB  - The goal of this study is to identify and describe variables contributing to the
      efficiency of health promotion interventions, and to assess whether these
      variables can serve as reliable and early indicators of the success of such
      interventions. The study sample includes 44 interventions selected through a
      network of key informants from five cities--Liverpool, Sandwell, Vienna, Pula,
      and Rijeka--by using a chain technique. Data on each intervention are collected
      through an in-depth interview with a program leader, the collection of project
      related documents, and on-site observation. Qualitative analysis of data
      performed with content analysis and computer-assisted free-text analysis reveals
      different characteristics of interventions depending on whether they are
      initiated by the city government sector, health-care system, or citizens sector
      (independent of the city or country). The assessment of the efficiency of these
      three groups of interventions also differs because of varying features, scope
      (activity potentials) and impact they are able to accomplish. We have identified
      ways in which the efficiency of all three groups of interventions can be
      improved. The efficiency of the interventions within the city sector can be
      increased through an improved process of delegation to other sectors, higher
      involvement of user groups, and higher receptivity and organizational
      flexibility. The efficiency of the interventions within the citizens sector can
      be improved through professional, organizational, and financial support. Support
      from the professional community is important for citizens sector interventions in
      confirming the importance of the problem they address and legitimizing the
      actions they propose and undertake.

PMID- 15482876
TI  - Does economic inequality affect child malnutrition? The case of Ecuador.
AB  - Economic inequality has been hypothesized to be a determinant of population
      health, independent of poverty and household income. We examined the association
      between economic inequality and child malnutrition in Ecuador. Economic
      inequality was measured by the Gini coefficient of household per capita
      consumption, estimated from the 1990 Census. Childhood stunting, assessed from
      height-for-age z scores, was obtained from the 1998 Living Standards Measurement
      Survey (LSMS). We controlled for a range of individual and household covariates,
      including per capita food consumption, education, housing, ethnicity, fertility,
      access to health services, diarrhea morbidity, child care, mother's age and diet
      composition. Stunting still affects 26% of children under five in Ecuador, with
      higher prevalence in the rural Highlands and among indigenous peoples. Maternal
      education, basic housing conditions, access to health services, ethnicity,
      fertility, maternal age and diet composition were independently associated with
      stunting. However, after controlling for relevant covariates, economic inequality
      at the provincial scale had a statistically significant deleterious effect on
      stunting. At municipal or local levels, inequality was not associated with
      stunting.

PMID- 15482877
TI  - Psychosocial distress of Tibetans in exile: integrating western interventions
      with traditional beliefs and practice.
AB  - A psychosocial care project for Tibetan torture survivor's and other Tibetan
      refugees suffering from psychological distress was opened in Dharamsala, North
      India in 1995 by a western non-government organisation (NGO) in collaboration
      with the Tibetan government-in-exile. The clinic explicitly sought to integrate
      western and local traditional approaches to healing. The aim of the present study
      was to examine the views of key stakeholders of the project in the context of
      broader cultural and social issues faced by exiled Tibetans. Twenty individual
      interviews were conducted with 'officials' (members of the Tibetan government-in
      exile, religious leaders, other community leaders, and senior medical staff), the
      staff of the project (Tibetan and western) and the clients themselves. The
      interviews were taped, transcribed, and analysed using a grounded theory
      approach. All interviewees considered that mental health was an important issue
      and that awareness of psychological health in the community had improved since
      the initiation of the project. Clients and staff of the project, and some of the
      'officials', believed that it provided a much-needed service and that it
      effectively and sensitively combined western psychological approaches with local
      cultural and religious beliefs and practices. However, a majority of the
      'officials' felt that mental health issues were not a top priority in the
      competing health needs of the community, and that other ways of dealing with such
      problems (using traditional approaches or local health services) were adequate.
      Given these and other factors, the longer-term sustainability of the project
      appears to be a major challenge. According to the users and providers
      interviewed, the current project has developed an important and beneficial
      psychosocial support service. However, the continuing debate amongst community
      leaders regarding the place and future of the project suggests the importance of
      accommodating the views and priorities of all local stakeholders--and focusing on
      sustainability and capacity building of relevant community members--from the
      outset of such projects. This includes acknowledging the perceived threat to
      traditional beliefs and coping strategies--particularly in the context of wider
      socio-cultural disruption--posed by initiatives seeking to integrate western
      intervention approaches with local healing resources.

PMID- 15482878
TI  - Are racial disparities in health conditional on socioeconomic status?
AB  - Racial health inequality is related to socioeconomic status (SES), but debate
      ensues on the nature of the relationship. Using the US National Health and
      Nutrition Examination Survey I and the subsequent follow-up interviews, this
      research examines health disparities between white and black adults and whether
      the SES/health gradient differs across the two groups in the USA. Two competing
      mechanisms for the conditional or interactive relationship between race and SES
      on health are examined during a 20-year period for black and white Americans.
      Results show that black adults began the study with more serious illnesses and
      poorer self-rated health than white adults and that the disparity continued over
      the 20 years. Significant interactions were found between race and education as
      well as race and employment status on health outcomes. The interaction effect of
      race and education showed that the racial disparity in self-rated health was
      largest at the higher levels of SES, providing some evidence for the "diminishing
      returns" hypothesis; as education levels increased, black adults did not have the
      same improvement in self-rated health as white adults. Overall, the findings
      provide evidence for the continuing significance of both race and SES in
      determining health status over time.

PMID- 15482879
TI  - Business cycles and mortality: results from Swedish microdata.
AB  - We assess the relationship between business cycles and mortality risk using a
      large individual level data set on over 40,000 individuals in Sweden who were
      followed for 10-16 years (leading to over 500,000 person-year observations). We
      test the effect of six alternative business cycle indicators on the mortality
      risk: the unemployment rate, the notification rate, the deviation from the GDP
      trend, the GDP change, the industry capacity utilization, and the industry
      confidence indicator. For men we find a significant countercyclical relationship
      between the business cycle and the mortality risk for four of the indicators and
      a non-significant effect for the other two indicators. For women we cannot reject
      the null hypothesis of no effect for any of the business cycle indicators.

PMID- 15482880
TI  - Molecular fluorescent approach to assessing intraerythrocytic hemoprotozoan
      Babesia canis infection in dogs.
AB  - The development of recent flow cytometry-based protocols for the diagnosis of
      canine babesiosis, Babesia gibsoni in particular, has encouraged us to
      investigate its applicability to detect B. canis-infected erythrocytes as well as
      optimize the hydroethidine-flow cytometry methodology (HE-FC), using peripheral
      blood samples from naturally and experimentally infected dogs. Our data
      demonstrated that HE at 25 microg/ml provided the most outstanding fluorescence
      profile, able to discriminate between infected and uninfected dogs with no
      alterations in cell properties such as forward scatter and unspecific
      fluorescence. The results were expressed as the percentage of positive
      fluorescent erythrocytes (PPFE) for each individual sample, with 1.53% of PPFE as
      the cut-off determined between infected and uninfected animals. B. canis-infected
      erythrocytes during both acute and chronic experimental infection were identified
      through HE-FC, validating its use for diagnosis purposes in endemic areas for
      canine babesiosis. In a clinical trial, 22.8% out of 162 dogs showed to be
      positive to Babesia infection through this approach. Such prevalence was similar
      to that estimated for altered hematological profiles (HT) < or = 30% (29%), but
      highly distinct from the prevalence provided by direct blood smear (BS)
      examination (1.8%) or immunofluorescent assay (IFA) (60.5%). Furthermore, our
      findings indicate that positive PPFE data was associated with HT < or = 30%,
      emphasizing that, in clinical practice, the haematocrit should be used as a
      screening test followed by HE-FC, suitable to confirm hypotheses of canine
      babesiosis.

PMID- 15482881
TI  - Epidemiological study of the prevalence of Babesia divergens in a veterinary
      practice in the mid-east of France.
AB  - To assess the epidemiology of Babesia divergens in a veterinary practice based in
      the mid-east of France ("Monts du Lyonnais"), blood was collected from 254 cattle
      belonging to 24 herds. To assess the dynamics of the carrier state, six carriers
      were identified, treated with flumethrin and sampled once every 3 weeks during 6
      months. Two different DNA extraction methods were compared. Each sample was
      tested for the presence of parasites using a PCR-RFLP test based on the 18S rRNA
      gene. The sensitivity of the test was equivalent to a parasitaemia as low as 10(
      5)% (in "Filter Paper" samples) and 10(-6)% in 1 ml blood (extracted using
      "Matrix"). With the latter method, the rate of detection diminishes in the low
      parasitaemia range but could probably be improved. This test proved to be very
      useful in the detection of B. divergens carriers. Serology using IFAT showed 7%
      of the cattle seropositive, which is suggestive of a disease situation with a low
      clinical risk level. Analysis of the PCR results suggests a 20% prevalence rate
      of carriers in the cattle population. The use of the mean parasitaemia is
      proposed to serve as a babesiosis clinical risk indicator. This approach could
      also be used in other babesia infections provided the lowest detectable
      parasitaemia level (threshold level) could be resolved for each parasite species.

PMID- 15482882
TI  - Comparison of different tissue sampling for PCR-based diagnosis and follow-up of
      canine visceral leishmaniosis.
AB  - In this study, different types of tissue sampling for PCR-based diagnosis and
      follow-up of canine visceral leishmaniosis were compared. Skin, whole blood and
      lymph node samples were collected from 95 naturally infected dogs living in South
      Italy, where the disease is endemic. Twenty-nine of these 95 dogs, treated with
      meglumine administered concurrently with allopurinol for 30 days, and then with
      allopurinol alone, were monitored during a period of 2 years. The DNA extracted
      from the clinical specimens was amplified by PCR using as target DNA a 116-bp
      fragment in the constant region of the kinetoplast DNA minicircle. PCR analysis
      was more sensitive than indirect immunofluorescence antibody test in detecting
      Leishmania infection in symptomatic dogs: 99% of lymph node samples resulted
      positive, whereas 94% of blood samples and 95% of skin samples gave a positive
      result. PCR analysis of samples from dogs followed up 2 years showed that: (1)
      all subjects resulted positive in at least one of the three types of samples; (2)
      all time the dogs had a relapse, PCR resulted positive in all three types of
      samples; (3) when dogs were apparently healthy, PCR analysis was positive on skin
      and lymph node samples, but not always on blood samples. Since lymph node
      sampling is invasive and sometimes difficult in healthy asymptomatic dogs, our
      results suggest that, independently from the presence or not of cutaneous
      lesions, skin biopsy represents a good substratum for PCR-based diagnosis and
      follow-up of canine visceral leishmaniosis.

PMID- 15482883
TI  - Enzootiology of Trypanosoma evansi in Pantanal, Brazil.
AB  - In order to better understand the enzootiology of trypanosomiasis caused by
      Trypanosoma evansi in the Brazilian Pantanal we examined domestic and wild
      mammals by microhematocrit centrifuge technique (MHCT), immunofluorescence
      antibody test (IFAT) and polymerase chain reaction (PCR). T. evansi infection was
      detected in all species sampled with exception of the sheep and the feral pig.
      High parasitemias were observed in capybaras (5/24), coatis (18/115), horses
      (31/321) and dogs (3/112). Among these species, only the capybaras did not
      develop anemia. Low parasitemias, only detected by PCR, were found in buffaloes
      (18/43), bovines (29/331), marsupials (1/4), small rodents (14/67), bats (7/18),
      and one armadillo (1/8). The highest prevalence of T. evansi infection was
      recorded in horses (73%), although no neurological signs in infected horses were
      observed. Diagnosis through standard parasitological tests and IFAT should be
      used with caution since they may overlook comprovedly infected horses. The
      relationship between ranch management and T. evansi infection in horse was
      investigated. The importance of other transmission mechanisms apart from the
      tabanids and reservoir hosts are discussed.

PMID- 15482884
TI  - Prevalence of and risk factors associated with the presence of Sarcocystis
      neurona sporocysts in opossum (Didelphis virginiana) from Michigan: a
      retrospective study.
AB  - From April 1996 to December 2002 the prevalence of Sarcocystis neurona sporocysts
      in North American opossum (Didelphis virginiana) in Southern Michigan was
      estimated. Sporocysts of S. neurona were found in intestinal scrapings from 31
      (15%) of 206 examined opossum. The frequency of infection was higher in adult
      animals (26/206; 12.6%) and females (19/206; 9.2%) than in juveniles (5/206;
      2.4%) and males (12/206; 5.8%). Also, prevalence of S. neurona sporocysts in
      opossums in relation to factors such as age, sex, season, body condition,
      presence of concomitant infection, and presence of young in the pouch of females
      was studied in detail over the course of the year, 2002. Univariate analyses
      identified the following factors as being associated with the presence of S.
      neurona sporocysts in opossums: (i) for age, adult (odd ratio [OR] = 2.074, P =
      0.0005); (ii) for sex, female (OR = 7.016, P = 0.0119); (iii) for season, summer
      (OR = 7.917, P = 0.0032) and spring (OR = 4.071, P = 0.1063); (iv) for body
      condition, poor (OR = 3.50, P = 0.1200) and good (OR = 1.167, P = 0.8637); (v)
      for the presence of concomitant infection (OR = 23.056, P = 0001), and (vi) for
      the presence of young in the pouch of females (OR = 40.083, P = 0.0001).
      Multivariate logistic-regression analyses selected the following factors as being
      significantly associated with presence of S. neurona sporocysts in opossums: (i)
      for the presence of concomitant infection (OR = 8.722, P = 0.0160) and (ii) for
      the presence of young in the pouch of females (OR = 31.915, P = 0.0065). The
      prevalence of S. neurona sporocysts in D. virginiana suggests that this opossum
      may constitute an ample reservoir of infection to other animals in the northern
      United States.

PMID- 15482885
TI  - Expression of anti-apoptotic factors in cells parasitized by second-generation
      schizonts of Eimeria tenella and Eimeria necatrix.
AB  - Intracellular infections by parasites require a functional anti-apoptotic
      mechanism for parasite survival within the host cell. The intracellular cycle of
      Eimeria tenella and Eimeria necatrix in chicken intestinal cells involves the
      maturation of schizonts within the epithelial cells lining the crypt lumen of the
      ceca (E. tenella) and jejunum (E. necatrix). After invasion, these cells detach
      from the epithelial layer and migrate into the underlying connective tissue,
      where maturation of second-generation schizonts takes place. However, the
      detached epithelial cells that harbour the parasite and localize in the lamina
      propia do not undergo apoptosis despite the fact that they are parasitized cells
      and are located in an inappropriate microenvironment. In this study we consider
      the hypothesis that E. tenella and E. necatrix may inhibit the host cell
      apoptosis that accompanies parasite-mediated transformation during late
      schizogony. To that end, the expression of both NF-kappaB, a transcriptional
      factor that blocks parasite-induced apoptosis, and bcl-xL, an anti-apoptotic
      protein induced by NF-kappaB, were studied in the host cell during the maturation
      of second-generation schizonts. In addition, the expression of the phosphorylated
      inhibitor of NF-kappaB, p-IkBalpha, was also studied to further confirm NF-kappaB
      activation. Immunocytochemical techniques, flow cytometric and blott analysis
      were applied by using polyclonal antibodies that specifically react with bcl-xL,
      p-IkBalpha, and NF-kappaB to detect these anti-apoptotic proteins in the
      parasitized cell. Our results offer evidence that both these coccidial species
      first induce NF-kappaB activation to protect the transformed parasitized cells
      from apoptosis, allowing the second-generation schizonts to mature, and later,
      after complete schizonts maturation, cause NF-kappaB inhibition to trigger host
      cell apoptosis in order to facilitate the escape of merozoites. To determine
      whether inhibition of the NF-kappaB pathway would induce apoptosis of the host
      cell, a protease inhibitor (TPCK), which induces apoptosis by mediating
      inhibition of IkB phosphorylation, was administered to parasitized chickens.

PMID- 15482886
TI  - Aspects of the early moments of interaction between tachyzoites of Toxoplasma
      gondii with neutrophils.
AB  - The interaction of the tachyzoite stage of Toxoplasma gondii with neutrophils was
      investigated. Morphological aspects of the initial moments of interaction were
      analyzed by transmission and scanning electron microscopy, revealing at least
      three types of reaction from the leukocytes to the parasite: the projection of
      filopodia, formation of a tunnel-like projection involving the parasite, and
      invagination of the leukocyte surface at the point of entry. The influence on
      infectivity of tyrosine kinase, phosphokinase C and phosphatidylinositol 3 kinase
      cell signaling pathways were studied with the aid of drugs affecting these
      enzymes in these cells.

PMID- 15482887
TI  - Specific IgG antibody response against antigens of Dirofilaria immitis and its
      Wolbachia endosymbiont bacterium in cats with natural and experimental
      infections.
AB  - Sera from three groups of cats under different experimental conditions were
      studied by ELISA to assess the host's immune response against synthetic peptides
      derived from Dirofilaria immitis (Dipp) and against the surface protein of its
      endosymbiont, Wolbachia (WSPr). In experimentally infected cats (Group 1), an
      increase of IgG antibody against both Dipp and WSPr was observed from 2 months
      post-infection until the end of the study, 6 months post-infection. In
      experimentally infected cats, treated against infective larvae (Group 2), anti
      Dipp IgG decreased dramatically from 4 months post-infection (3 months post
      treatment), showing very low values till the end of the study (6.5 months from
      infection, 5.5 months from treatment), while anti-WSP IgG increased constantly
      till the end of the study. Of 49 outdoor, asymptomatic cats exposed to a high
      risk of natural infection (Group 3), 9 were positive for anti-Dipp IgG and for a
      validated, in-clinic commercial antibody diagnostic kit for cats. Two cats were
      also found positive for circulating antigens of adult female worm. Anti-WSPr IgG
      were found in five of nine anti-Dipp IgG-positive sera and from eight ELISADipp
      negative sera. Our results confirm the strong IgG response in heartworm infected
      cats and demonstrate the involvement of the Wolbachia endosymbiont in the immune
      reaction to the parasite both in experimentally infected cats and in cats exposed
      to a high risk of natural infection.

PMID- 15482888
TI  - Toxocara canis in experimentally infected pigs: migratory pattern and tissue
      lesions.
AB  - Fifteen Yorkshire female pigs were inoculated with 100,000 infective T. canis
      eggs. Three animals were used as uninfected controls. Groups of three infected
      pigs were euthanized by accepted methods on days 7, 14, 21, 28 and 126 p.i.,
      respectively. Larvae were recovered from all animals included in each group
      slaughtered on days 7 and 14 p.i.; on day 21 p.i. from two pigs, on day 28 p.i.
      from one, and no larvae were found on day 126 p.i. Differences in the mean number
      of larvae per gram in lymph nodes, liver and lungs between slaughter days, were
      significant for livers on day 7 p.i. and for lungs on day 14 p.i. (P < 0.10). The
      decrease over time was significant in all the organs that previously had larvae.
      Larvae were not found in the other organs and tissues analysed. Macroscopical
      lesions were found in the liver, lungs and lymph nodes on days 7, 14, 21, and 28
      p.i. The entire surface of the liver was covered with small white spots on day 7
      p.i., on days 14 and 21 p.i. the spots were distinctly nodular and, in some
      places, individual lesions were confluent. Lesions had apparently started to heal
      on days 28 and 126 p.i. appearance was normal. Lymph nodes were enlarged and
      oedematous during the first 4 weeks and the lungs had small areas of
      consolidation visible all over the surface, but by day 126 p.i., no visible
      lesions could be seen. Microscopical lesions were observed in the liver on day 7
      p.i., with a largely periportal hepatitis. Numerous eosinophils and lymphocytes
      were present. The typical granulomatous reaction was observed on days 14 and 21
      p.i. with a central necrotic core and a narrow region of fibroblastic tissue. By
      day 28 p.i. lesions had almost disappeared and the number of eosinophils was
      fewer. There were fewer leukocytes and the fibrous tissue had disappeared from
      the liver on day 126 p.i. For the first 3 weeks, pictures of the lymph nodes and
      the lungs were characterised by the formation of a granuloma. In the center of
      the granuloma larvae were observed. The majority of the lesions had healed by day
      126 p.i.

PMID- 15482889
TI  - Trichinella pseudospiralis foci in Sweden.
AB  - In Sweden, the prevalence of Trichinella infection in domestic pigs has greatly
      decreased since the 1970s, with no reports in the past 4 years. However, infected
      wild animals continue to be found. The objective of the present study was to
      identify the species of Trichinella present in animals of Sweden, so as to
      contribute to the knowledge on the distribution area and hosts useful for the
      prevention and control of this zoonosis. In the period 1985-2003, Trichinella
      larvae were detected in the muscles of 81/1800 (4.5%) red foxes (Vulpes vulpes),
      1/6 (16.7%) arctic fox (Alopex lagopus), 1/7 (14.3%) wolf (Canis lupus), 10/200
      (5.0%) lynxes (Lynx lynx), 4/8000 (0.05%) wild boars (Sus scrofa), and 27/66 x
      10(6) (0.000041%) domestic pigs. All four Trichinella species previously found in
      Europe were detected (Trichinella spiralis, T. nativa, T. britovi and T.
      pseudospiralis). The non-encapsulated species T. pseudospiralis was detected in
      three wild boars from Holo (Stockholm area) and in one lynx from Froso (Ostersund
      area), suggesting that this species is widespread in Sweden. These findings are
      consistent with those of a study from Finland, both for the unexpected presence
      of T. pseudospiralis infection and the presence of the same four Trichinella
      species, suggesting that this epidemiological situation is present in the entire
      Scandinavian region. The widespread diffusion of T. pseudospiralis in the
      Scandinavian region is also important in terms of it potential impact on public
      health, given that human infection can occur and the difficulties to detect it by
      the trichinelloscopic examination.

PMID- 15482890
TI  - Seroprevalence of Dictyocaulus viviparus in first grazing season calves in
      Sweden.
AB  - A serological survey was carried out to determine the prevalence and geographical
      distribution of Dictyocaulus viviparus in calves after their first grazing season
      in Sweden. A total of 754 animals from 76 randomly selected herds in seven
      geographical regions were examined between September 24 and December 19, 2001. To
      get an indication about the geographical distribution of the infection 41 herds
      with beef-suckler calves were investigated. On each farm, blood was collected
      from 8 to 10 animals after an average of 26 +/- 24 days post-housing to determine
      specific IgG1 levels against a possible lungworm sperm antigen that is highly
      specific against patent infections of D. viviparus. We also investigated the
      seroprevalence of lungworm infection in relation to cattle management. In one
      region additional samples were analysed from 35 herds either with: (a) beef
      suckling calves that were dewormed at housing, (b) untreated organically raised
      dairy calves, and finally from conventionally raised dairy calves either, (c)
      with or, (d) without a prophylactic anthelmintic treatment programme against
      gastrointestinal parasites on pasture. A questionnaire was used to obtain
      information about herd size and management, including measures to control
      nematode parasites on the farm. A total of 86 (11.8%) out of 754 animals had
      antibodies against D. viviparus, and at least one infected individual was
      detected in 30 (39.5%) of the 76 herds examined. Lungworm infected animals were
      found throughout the country and there was no significant differences between
      regions, although in southern and southwestern Sweden 70.0% of the herds were
      infected. Furthermore, there were no major differences in the seroprevalence in
      relation to management. Between 40.0 and 44.4% of the herds were infected
      irrespective of management, with the exception of calves from organic herds where
      no seropositive samples were found (0%). This result is in contrast to previous
      findings of lungworms in Sweden, and indicates that the parasite status on
      organic farms is diverse.

PMID- 15482891
TI  - Impact of eprinomectin on grazing behaviour and performance in dairy cattle with
      sub-clinical gastrointestinal nematode infections under continuous stocking
      management.
AB  - Forty spring-calving cows and heifers (20 of each) were allowed to acquire
      infection with gastrointestinal (GI) nematodes naturally during grazing. The
      control group (10 cows and 10 heifers) were compared with 20 similar animals
      treated with eprinomectin in order to evaluate the effect of GI nematodes on
      grazing behaviour, milk production, body condition score and live weight. The
      animals were paired according to parity and milk yield during the week prior to
      treatment, then within replicate pair randomly allocated to a different treatment
      group. The grazing area was sub-divided into 20 replicated paddocks of equivalent
      size and topography. Grazing pairs of either control or treated animals were
      randomly assigned to each paddock over the duration of the study (one pair per
      paddock). Grazing behaviour was recorded for both groups over a 10-day period
      commencing 4 days after treatment with eprinomectin. Milk yield was recorded
      daily and milk quality was recorded weekly. Live weight and body condition score
      were recorded on the day of allocation, the day of initial treatment and
      thereafter at weekly intervals until the end of the 4-week trial. Faecal samples
      were collected from each animal prior to, and after, allocation and submitted for
      counts of nematode eggs. Additional faecal samples were taken at the end of the
      study for culture and nematode identification. Individual faecal samples were
      also analysed for residual digestibility. Pasture samples for nematode larval
      counts were taken at the same time as faecal sampling. The parasitological
      results showed low levels of faecal nematode egg output throughout the study,
      with the heifers having higher counts than the cows. Faecal culture yielded
      species of Ostertagia, Cooperia, and Trichostrongylus. Pasture larval levels were
      very low throughout with no value exceeding 68 larvae/kg dry matter (DM) of
      herbage. There were significant (P < 0.05) effects of treatment on grazing time,
      eating time, total bites, total grazing jaw movements (TGJM), idling time and
      mean meal duration. Treated cows and heifers grazed for 47 and 50 min longer per
      day, respectively, than controls (P = 0.016). Mean meal duration was extended as
      a result of anthelmintic treatment by 11 and 38 min, in cows and heifers,
      respectively (P = 0.012). There were no significant (P > 0.05) treatment effects
      on ruminating time or residual faecal digestibility, but idling time was
      significantly reduced in both treated cows and heifers, by 50 and 110 min,
      respectively (P = 0.010). In the treated cattle, there was an increase in solids
      corrected milk yield compared with the control cattle, which was significant (P <
      0.05) in weeks 2 and 3 after treatment. The response was particularly marked in
      heifers, where the difference in yield between treated and controls was up to
      2.35 kg/day. The differences in live weight gain and condition score over 28 days
      post-treatment were significant (P < 0.05) in both cows and heifers, in favour of
      the treated animals.

PMID- 15482892
TI  - First isolation and molecular characterization of Ehrlichia canis in Spain.
AB  - This paper reports the first isolation and culture of Ehrlichia canis in Spain
      from a naturally infected dog using the DH82 cell line. After DNA extraction and
      PCR amplification, a nearly complete (1412bp) sequence of the 16S rRNA gene of
      the new E. canis strain was obtained. The GenBank accession number for the
      nucleotide sequence of this strain is AY394465. This sequence was aligned with
      the 16S rRNA gene sequences of other Ehrlichia strains accessible in GenBank. The
      16S rRNA gene sequence of the E. canis strain reported here showed a high
      percentage of similarity with the 16S rRNA gene sequence of E. canis from
      different geographic areas including Japan, Venezuela and Israel. These data
      confirm the presence of E. canis in Spain.

PMID- 15482893
TI  - Evaluation of the prophylactic effect and curative efficacy of fipronil 1% pour
      on (Topline) on post-castration scrotal myiasis caused by Cochliomyia hominivorax
      in cattle.
AB  - A field trial was carried out during a summer-fall period on a commercial beef
      cattle farm in Minas Gerais State, located in the Southeast of Brazil. In order
      to evaluate the prophylactic effect and the curative efficacy of fipronil in a 1%
      solution, 200 Zebu crossbred bulls, with ages varying from 20 to 30 months and
      weights from 233 to 362 kg, were selected. The bulls were assigned by ranked pair
      to an untreated control group (A) or to a treated group (B), resulting in 100
      animals per group. All experimental animals were surgically castrated on day 0,
      following routine procedures. After castration all animals in the group B were
      treated with 10 mg/kg bw of a 1% fipronil solution, topically on the dorsal mid
      line. The wounds were individually inspected on days: 2, 4, 7, 10, 14, 17, 21, 28
      and 35. After castration the animals were naturally exposed to Cochliomyia
      hominivorax and remained in the same pasture throughout the trial. Among the
      animals in the control group, 83 were observed to harbor C. hominivorax eggs,
      with a total of 97 ovipositions, and among those 73 animals had active myiasis.
      In group B (fipronil 1%), 66 animals showed C. hominivorax eggs, with 92
      ovipositions and five animals with active myiasis. Most ovipositions and active
      myiasis were detected until seven days post-castration for both groups. Wound
      parasite infestation evidenced bleeding, serous purulent exudation and presence
      of active C. hominivorax larvae. Treatment with fipronil 1% had a prophylactic
      effect on scrotal wounds against the development of C. hominivorax larvae in more
      than 95% of the treated animals for up to 17 days after castration. The treatment
      showed partial protection of 66% and 50% on days 21 and 28 post-treatment (pt),
      respectively. Three animals from the control group and one from the treated group
      showed active screwworms on day 21 pt, and one animal from the treated group and
      two from the control group also presented C. hominivorax larvae on scrotal wounds
      on day 28 pt. By the end of the observation period (day 35 pt), the castration
      wound had healed in all animals. All experimental animals presenting scrotal
      wounds infested with C. hominivorax larvae were treated with a 1% pour-on
      formulation of fipronil, on the same day that infestation was observed. Active C.
      hominivorax larvae were not seen during the monitoring period immediately after
      treatment. The curative efficacy of fipronil 1% against C. hominivorax larvae
      infestation in castration wounds was 100%.

PMID- 15482894
TI  - Morphological characterization of the ovary and vitellogenesis dynamics in the
      tick Amblyomma cajennense (Acari: Ixodidae).
AB  - In this work we describe the internal morphology of the female reproductive
      system of the cayenne tick Amblyomma cajennense. This system is represented by a
      panoistic ovary, which lacks nurse cells in the germarium. This ovary consists of
      a single tube, in which a large number of oocytes develop asynchronously, thus
      accompanying the processes of yolk deposition in the oocytes. The oocytes were
      classified into stages that varied from I to V, according to: cytoplasm
      appearance, presence of the germ vesicle, presence of yolk granules, and presence
      of chorion. The study of vitellogenesis dynamics suggest that the yolk elements
      are deposited in the oocyte following a preferencial sequence, in which the
      lipids are the first to appear, followed by proteins an finally by the
      carbohydrates. In this way the yolk of A. cajennense ticks have these three
      elements that may be free in the cytoplasm or chemically bounded forming
      glycoprotein or lipoprotein complexes.

PMID- 15482895
TI  - Efficacy of fipronil/(S)-methoprene combination spot-on for dogs against shed
      eggs, emerging and existing adult cat fleas (Ctenocephalides felis, Bouche).
AB  - The inhibitory activities of fipronil (10% (w/v) solution), (S)-methoprene (9%
      (w/v) solution), and fipronil/(S)-methoprene (10 and 9% (w/v) solution,
      respectively) combination against eggs and emerging adult cat fleas
      (Ctenocephalides felis) and adulticidal activity were tested on experimentally
      infested dogs. Thirty-two Beagle dogs were selected for this study and eight
      replicates of four animals were formed based on body weight within sex. One dog
      in each replicate was randomly allocated to treatment with: (1) untreated
      control; (2) fipronil 10% (w/v) solution, (3) (S)-methoprene 9% (w/v) solution,
      and (4) fipronil 10% (w/v) and (S)-methoprene 9% (w/v) combination solution.
      Treatments were applied once topically on Day 0 at the rate of 0.067 ml/kg. On
      Days -12, -1, 21, and weekly to Day 84 each dog was infested with approximately
      200 fleas and comb counted approximately 24h later, or 2 days (our 48 h) after in
      the case of Day -1 infestation. On Days -11, 1, 22, and weekly to Day 85 each dog
      was again infested with approximately 200 fleas. Flea eggs were collected over
      approximately 24 h beginning 3 days after infestation. Fleas were combed off of
      the dogs and counted at the end of the egg collection period (approximately 96 h
      count). One aliquot of up to about 100 eggs, if available, from each animal at
      each infestation time was incubated for approximately 72 h to determine larval
      hatch and the other for 35 days to determine the number of adults that developed.
      The 10% (w/v) fipronil spot-on provided excellent control (>95%) of adult fleas
      on dogs for 5 weeks. Similarly, the combination spot-on of 10% (w/v) fipronil and
      9% (w/v) (S)-methoprene provided excellent control of adult fleas, i.e., >95% for
      5 weeks. From week 6 post-treatment onward, the relatively low inhibition of
      adult flea emergence substantiated the lack of significant ovicidal/larvicidal
      activity in the fipronil (10%, w/v) treatment group. However, the combination
      product provided excellent (>90%) ovicidal activity for 8 weeks and high (91.4%)
      inhibition of adult flea emergence for 12 weeks. In addition, a synergistic
      effect of the two compounds in combination was demonstrated with fipronil
      enhancing the ovicidal and inhibition of adult flea emergence activity of (S)
      methoprene against cat flea eggs. When all stages of the life cycle of the cat
      flea are considered, the combination spot-on product provided a high level of
      total flea control yielding a curative effect against adult fleas and inhibition
      of flea development stages with little to no potential reinfestation pressure on
      the animal or in the environment for 12 weeks.

PMID- 15482896
TI  - Anti-protozoal efficacy of high performance liquid chromatography fractions of
      Torilis japonica and Sophora flavescens extracts on Neospora caninum and
      Toxoplasma gondii.
AB  - We previously reported that alcoholic extracts of Sophora flavescens and Torilis
      japonica from South Korea demonstrated good efficacy in reducing replication of
      Toxoplasma gondii and Neospora caninum. To characterize the chemical component
      associated with anti-protozoal activity, specific fractions were isolated by high
      performance liquid chromatography (HPLC) and used for in vitro testing. These
      fractions were evaluated in vitro against T. gondii and N. caninum. Fractions of
      the herb extracts were serially diluted to final concentrations of 2.850 to 0.356
      ng/ml in medium and added to wells containing replicating T. gondii and N.
      caninum. To determine the ability of each fraction to inhibit parasite
      proliferation, 3H-uracil incorporation was used to determine parasite
      replication. In cultures infected with T. gondii, a fraction of T. japonica (TJ2)
      inhibited T. gondii proliferation by 99.2, 94.4, 88.6 and 27.0% in the range from
      2.850 to 0.356 ng/ml. Four fractions of S. flavescens (SF1-SF4) inhibited T.
      gondii proliferation by 99.6-60.6, 96.9-48.1, 92.3-68.2 and 95.4-52.9% in the
      range from 2.850 to 0.356 ng/ml. In cultures infected with N. caninum, a fraction
      of T. japonica (TJ2) inhibited N. caninum proliferation by 98.3, 95.5, 79.7 and
      30.6% in the range from 2.850 to 0.356 ng/ml. Four fractions of S. flavescens
      (SF1-SF4) inhibited N. caninum proliferation by 97.1-25.9, 94.8-35.5, 95.9-33.7
      and 95.4-49.4% in the range from 2.850 to 0.356 ng/ml. These fractions of T.
      japonica and S. flavescens extracts are currently undergoing in vivo evaluation
      in experimentally infected mice.

PMID- 15482897
TI  - Duration of activity of topical eprinomectin against experimental infections with
      Teladorsagia circumcincta and Trichostrongylus colubriformis in goats.
AB  - The immediate as well as the persistent anthelmintic efficacies of topically
      applied eprinomectin were evaluated in goats against induced infections with
      Teladorsagia circumcincta (2800 L3) and Trichostrongylus colubriformis (6000 L3).
      Twenty-three culled dairy goats were allocated to the following groups: control
      animals (group 1), animals treated 21 days prior to nematode infection (group 2),
      animals treated 7 days prior to nematode infection (group 3) and animals treated
      21 days after nematode infection (group 4). Eprinomectin was applied at twice the
      cattle dose rate (1.0 mg/kg BW). According to the groups, necropsies were
      undertaken 28 days after nematode infection (groups 1-3) or 14 days after the
      anthelmintic treatment (group 4). Worm counts were determined for abomasum and
      small intestine. The curative anthelmintic efficacy of eprinomectin at 1.0 mg/kg
      BW on existing worm burdens was 100% against T. circumcincta and T.
      colubriformis. Quite similar worm burdens reductions were observed when
      eprinomectin was administered 7 days before infection whereas they were only 52.4
      and 17.8% for T. circumcincta and T. colubriformis, respectively, for an
      administration of the drug 21 days prior to the nematode infection.

PMID- 15482898
TI  - The distribution of m4 muscarinic acetylcholine receptors in the islands of
      Calleja and striatum of rats and cynomolgus monkeys.
AB  - The distribution of m4 muscarinic acetylcholine receptors, and their relation to
      a number other markers, was examined using immunocytochemical techniques.
      Staining in the dorsal striatum tended to be more pronounced in the striosomal
      than the matrix compartment of both rats and cynomolgus monkeys. Within the
      ventral striatum, immunoreactivity was more pronounced within the olfactory
      tubercle and the shell region of the nucleus accumbens than in the nucleus
      accumbens core and was especially marked within the lateral striatal stripe.
      Modest staining was also seen in the external plexiform layer of the olfactory
      bulb. By far, the most intense staining in the forebrain of both rats and
      cynomolgus monkeys was found in islands of Calleja, where it appeared to be a
      selective marker for the core or hilus regions of the islands, or an analogous
      region found adjacent to them. The core regions of different islands appear to be
      continuous with each other so as to form a complex three-dimensional structure,
      which is largely encased by layers of granule cells. The neuronal elements in the
      islands of Calleja, which express m4 receptors, remain to be identified, but it
      is unlikely that cholinergic neurons are a major locus of these receptors.
      Although there are certain similarities between the islands of Calleja and other
      components of the striatal complex, the current studies emphasize the extent to
      which the islands are unique in terms of their architecture and chemical anatomy.

PMID- 15482899
TI  - Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in
      the adult rat brain--an immunohistochemical study.
AB  - The aim of this work was to study the distribution and cellular localization of
      GLUT2 in the rat brain by light and electron microscopic immunohistochemistry,
      whereas our ultrastructural observations will be reported in a second paper.
      Confirming previous results, we show that GLUT2-immunoreactive profiles are
      present throughout the brain, especially in the limbic areas and related nuclei,
      whereas they appear most concentrated in the ventral and medial regions close to
      the midline. Using cresyl violet counterstaining and double immunohistochemical
      staining for glial or neuronal markers (GFAp, CAII and NeuN), we show that two
      limited populations of oligodendrocytes and astrocytes cell bodies and processes
      are immunoreactive for GLUT2, whereas a cross-reaction with GLUT1 cannot be ruled
      out. In addition, we report that the nerve cell bodies clearly immunostained for
      GLUT2 were scarce (although numerous in the dentate gyrus granular layer in
      particular), whereas the periphery of numerous nerve cells appeared labeled for
      this transporter. The latter were clustered in the dorsal endopiriform nucleus
      and neighboring temporal and perirhinal cortex, in the dorsal amygdaloid region,
      and in the paraventricular and reuniens thalamic nuclei, whereas they were only a
      few in the hypothalamus. Moreover, a group of GLUT2-immunoreactive nerve cell
      bodies was localized in the dorsal medulla oblongata while some large multipolar
      nerve cell bodies peripherally labeled for GLUT2 were scattered in the caudal
      ventral reticular formation. This anatomical localization of GLUT2 appears
      characteristic and different from that reported for the neuronal transporter
      GLUT3 and GLUT4. Indeed, the possibility that GLUT2 may be localized in the sub
      plasmalemnal region of neurones and/or in afferent nerve fibres remains to be
      confirmed by ultrastructural observations. Because of the neuronal localization
      of GLUT2, and of its distribution relatively similar to glucokinase, it may be
      hypothesized that this transporter is, at least partially, involved in cerebral
      glucose sensing.

PMID- 15482900
TI  - Immunocytochemical localization of the glucose transporter 2 (GLUT2) in the adult
      rat brain. II. Electron microscopic study.
AB  - Following a former immunohistochemical study in the rat brain [Arluison, M.,
      Quignon, M., Nguyen, P., Thorens, B., Leloup, C., Penicaud, L. Distribution and
      anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat
      brain. I. Immunohistochemical study. J. Chem. Neuroanat., in press], we have
      analyzed the ultrastructural localization of GLUT2 in representative and/or
      critical areas of the forebrain and hindbrain. In agreement with previous
      results, we observe few oligodendrocyte and astrocyte cell bodies discretely
      labeled for GLUT2 in large myelinated fibre bundles and most brain areas
      examined, whereas the reactive glial processes are more numerous and often
      localized in the vicinity of nerve terminals and/or dendrites or dendritic spines
      forming synaptic contacts. Only some of them appear closely bound to unlabeled
      nerve cell bodies and dendrites. Furthermore, the nerve cell bodies prominently
      immunostained for GLUT2 are scarce in the brain nuclei examined, whereas the
      labeled dendrites and dendritic spines are relatively numerous and frequently
      engaged in synaptic junctions. In conformity with the observation of GLUT2
      immunoreactive rings at the periphery of numerous nerve cell bodies in various
      brain areas (see previous paper), we report here that some neuronal perikarya of
      the dorsal endopiriform nucleus/perirhinal cortex exhibit some patches of
      immunostaining just below the plasma membrane. However, the presence of many
      GLUT2-immunoreactive nerve terminals and/or astrocyte processes, some of them
      being occasionally attached to nerve cell bodies and dendrites, could also
      explain the pericellular labeling observed. The results here reported support the
      idea that GLUT2 may be expressed by some cerebral neurones possibly involved in
      glucose sensing, as previously discussed. However, it is also possible that this
      transporter participate in the regulation of neurotransmitter release and,
      perhaps, in the release of glucose by glial cells.

PMID- 15482901
TI  - Chemical divisions in the medial geniculate body and surrounding paralaminar
      nuclei of the rat: quantitative comparison of cell density, NADPH diaphorase,
      acetyl cholin esterase and basal expression of c-fos.
AB  - Quantitative methods of cell density, the intensities of both acetyl
      cholinesterase (AChE) and NADPH diaphorase (NADPHd), as well as the basal
      expression of c-fos, have been carried out in order to study the anatomical
      divisions of the medial geniculate body (MGB) and the group of nuclei located
      ventromedially to the MGB called the paralaminar complex (PL). The MGB was
      composed of the dorsal (MGd), and the ventral (MGv) divisions. We included the
      medial, or the magnocellular division (MGm), in the PL complex. MGd was composed
      of a dorsolateral (DL) core and a belt. The belt was composed of the
      suprageniculate (SG), the deep dorsal (DD), the caudo-medial (CM) and the caudo
      dorsal (CD) nuclei. In the MGv, the basal expression of c-fos was the only way to
      trace a clear boundary between the ovoid (Ov) and the ventrolateral (VL)
      divisions. However, the marginal zone (MZ) was clearly and contrastingly
      different. The PL was considered to be composed of: the MGm, the posterior
      intralaminar nucleus (PIN), the peripeduncular nucleus (PP) and the nucleus
      subparafascicularis lateralis (SPFL). The MGm and the PIN share most of the
      chemical features, meanwhile both SPFL and PP displayed different patterns of
      NADPHd reactivity. The study of cell density on Giemsa stained sections confirmed
      main divisions of the area. AChE and NADPHd methods allowed the main MGB
      divisions to be discriminated. The differences between subdivisions were
      emphasized when cell density and c-fos activity were quantified in each nucleus.
      Each MGB division displayed a different pattern of c-fos activity under basal
      conditions. Thus, c-fos basal expression was a particular feature in each MGB or
      PL nucleus.

PMID- 15482902
TI  - NMDA and AMPA/KA receptors are involved in the c-Fos expression following mustard
      oil activation of C-fibres.
AB  - To examine whether mustard oil application to the skin activated c-Fos via
      glutamate receptors, a competitive NMDA receptor antagonist, 3-(2-carboxpiperazin
      4-yl)propyl-1-phospionic acid (CPP), a selective AMPA/KA receptor antagonist, 6
      cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX), or both, were used intrathecally
      10 min prior to noxious stimulation. Application of mustard oil to left hind foot
      of the vehicle-injected animals produced c-Fos expression mainly in superficial
      laminae (laminae I-II) of the dorsal horn on the side ipsilateral to the
      stimulation. CPP significantly reduced the number of c-Fos-positive nuclei in
      superficial laminae. But significant reduction of c-Fos expression by CNQX was
      seen in deeper laminae (laminae III-X). Administration of both CPP and CNQX
      extensively reduced the number of c-Fos-positive cells in both superficial and
      deeper laminae. However, they did not greatly change the number of c-Fos-positive
      cells in lamina I. This experiment revealed that NMDA and AMPA/KA receptors
      contribute to the mustard oil-induced c-Fos expression in the spinal cord. These
      data also suggest that other neurotransmitter receptors might be involved in the
      activation produced by algesic chemical activation of C-fibre primary afferents.

PMID- 15482903
TI  - Fatty acid amide hydrolase in brain ventricular epithelium: mutually exclusive
      patterns of expression in mouse and rat.
AB  - Fatty acid amides and fatty acid ethanolamides are novel signalling molecules
      exemplified by the sleep-inducing lipid oleamide and the endocannabinoid
      anandamide, respectively. These substances are inactivated by fatty acid amide
      hydrolase (FAAH), an enzyme that is expressed by neurons and non-neuronal cells
      in the brain. In the rat, FAAH-immunoreactivity has been detected in epithelial
      cells of the choroid plexus and, in accordance with this finding, here we report
      FAAH mRNA expression in rat choroid plexus epithelium using in situ hybridisation
      methods. Surprisingly, a comparative analysis of mouse brain did not reveal FAAH
      mRNA expression or FAAH-immunoreactivity in the choroid plexus of this species.
      FAAH-immunoreactivity was, however, detected in non-choroidal ventricular
      ependymal cells in the mouse brain and the specificity of this immunostaining was
      confirmed by analysis of FAAH-knockout mice. FAAH-immunoreactivity was detected
      in ependymal cells throughout the ventricles of the mouse brain but with regional
      variation in the intensity of immunostaining. Intriguingly, in rat brain,
      although FAAH expression is observed in choroid plexus epithelial cells, little
      or no FAAH-immunoreactivity is present in the ventricular ependyma. Thus, there
      are mutually exclusive patterns of FAAH expression in the ventricular epithelium
      of rat and mouse brain. Our observations provide the basis for an experimental
      analysis that exploits differences in FAAH expression in rat and mouse to
      investigate FAAH function in ventricular epithelial cells and, in particular, the
      role of FAAH in regulating the sleep-inducing agent oleamide in cerebrospinal
      fluid.

PMID- 15482904
TI  - Examining the correlations between GSK-3 inhibitory properties and anti
      convulsant efficacy of valproate and valproate-related compounds.
AB  - A family of compounds based upon the chemical structure of valproate were
      synthesized and assayed for their ability to inhibit glycogen synthase kinase
      (GSK)-3 alpha and beta activity in vitro. This data is correlated to the known
      anti-convulsant properties of these compounds in order to determine the potential
      role of GSK-3 inhibition in the therapeutic efficacy of these drugs.

PMID- 15482905
TI  - Determination of the enantiomeric purity of the phytoalexins spirobrassinins by
      1H NMR using chiral solvation.
AB  - A simple and inexpensive method for enantiomeric discrimination of the
      phytoalexins spirobrassinin (1), 1-methoxyspirobrassinin (2) and synthetic analog
      1-methylspirobrassinin (6) using the chiral solvating agent 2,2,2-trifluoro-1-(9
      anthryl)ethanol in C(6)D(6) is described. Using this method the enantiomeric
      composition of each sample can be determined accurately by (1)H NMR and the
      compounds can be recovered readily by chromatography.

PMID- 15482906
TI  - 2-(2-[3-(pyridin-3-yloxy)phenyl]-2H-tetrazol-5-yl) pyridine: a highly potent,
      orally active, metabotropic glutamate subtype 5 (mGlu5) receptor antagonist.
AB  - Structure-activity relationship studies on 3-(5-pyridin-2-yl-2H-tetrazol-2
      yl)benzonitrile 2 led to the discovery of 2-(2-[3-(pyridin-3-yloxy)phenyl]-2H
      tetrazol-5-yl)pyridine (10)-a highly potent and selective mGlu5 receptor
      antagonist with good brain penetration and in vivo receptor occupancy in rat and
      cross-species oral bioavailability.

PMID- 15482907
TI  - 3-[3-Fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)phenyl]-4-methylpyridine: a highly
      potent and orally bioavailable metabotropic glutamate subtype 5 (mGlu5) receptor
      antagonist.
AB  - Structure-activity relationship studies performed around 3-fluoro-5-(5-pyridin-2
      yl-2H-tetrazol-2-yl)benzonitrile for the purpose of developing novel mGlu5
      receptor antagonists are described. Synthesis of a series of four-ring tetrazoles
      led to the discovery of 3-[3-fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)phenyl]-4
      methylpyridine, a highly potent, brain penetrant, azole-based mGlu5 receptor
      antagonist.

PMID- 15482908
TI  - Discovery of highly potent, selective, orally bioavailable, metabotropic
      glutamate subtype 5 (mGlu5) receptor antagonists devoid of cytochrome P450 1A2
      inhibitory activity.
AB  - Structure-activity relationship studies focused on bio-isosteric replacements of
      2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of
      cytochrome P450 1A2. This led to highly potent, selective and orally bioavailable
      2-imidazolyl tetrazoles such as (10) that are devoid of cytochrome P450
      inhibitory activity.

PMID- 15482909
TI  - Expedited SAR study of an mGluR5 antagonists: generation of a focused library
      using a solution-phase Suzuki coupling methodology.
AB  - The SAR of the lead compounds 2a and 2b was rapidly explored. Utilizing a
      parallel solution-phase Suzuki coupling approach, in tandem with strong cation
      exchange resin (SCX) purification afforded the desired focused library. The
      library was evaluated in vitro, a ninefold potency increase was achieved and the
      preference for ortho substitution of moderate steric bulk of the fourth, phenyl
      ring was identified. In addition, dimethylisoxazole, as a heterocyclic
      replacement for the phenylic ring of the lead compound, was also identified by
      this approach.

PMID- 15482910
TI  - Parallel synthesis of acylsemicarbazide libraries: preparation of potent cyclin
      dependent kinase (cdk) inhibitors.
AB  - Potent cyclin dependent kinase inhibitors were prepared using parallel synthesis
      methodology. Treating advanced intermediate 2 with a variety of hydrazides in
      DMSO at 80 degrees C for 30 min gave the desired acylsemicarbazides in good to
      excellent yield. Several compounds were active against cdk4/D1 and cdk2/E in the
      low nanomolar range. The SAR indicates a wide variety of substituents are
      tolerated at the acylsemicarbazide moiety.

PMID- 15482911
TI  - Parallel methods for the preparation and SAR exploration of N-ethyl-4-[(8-alkyl-8
      aza-bicyclo[3.2.1]oct-3-ylidene)-aryl-methyl]-benzamides, powerful mu and delta
      opioid agonists.
AB  - Two parallel synthetic methods were developed to explore the structure-activity
      relationships (SAR) of a series of potent opioid agonists. This series of
      tropanylidene benzamides proved extremely tolerant of structural variation while
      maintaining excellent opioid activity. Evaluation of several representative
      compounds from this series in the mouse hot plate test revealed potent
      antinociceptive effects upon oral administration.

PMID- 15482912
TI  - 1-(2-Aminoethyl)-3-(arylsulfonyl)-1H-indoles as novel 5-HT6 receptor ligands.
AB  - Novel 1-(2-aminoethyl)-3-(arylsulfonyl)-1H-indoles were prepared. Binding assays
      indicated they are 5-HT(6) receptor ligands, among which N,N-dimethyl-N-(2-[3-(1
      naphthylsulfonyl)-1H-indol-1-yl]ethyl)amine 8t and N-methyl-N-(2-[3-(1
      naphthylsulfonyl)-1H-indol-1-yl]ethyl)amine 8u showed high affinity for 5-HT(6)
      receptors with K(i)=3.7 and 5.7 nM, respectively.

PMID- 15482913
TI  - A 13C NMR approach to categorizing potential limitations of alpha,beta
      unsaturated carbonyl systems in drug-like molecules.
AB  - Compounds that contain an alpha,beta-unsaturated carbonyl moiety are often
      flagged as potential Michael acceptors. All alpha,beta-unsaturated carbonyl
      moieties are not equivalent, however, and we sought to better understand this
      system and its potential implications in drug-like molecules. Measurement of the
      (13)C NMR shift of the beta-carbon and correlation to in vitro results allowed
      compounds in our collection to be categorized as potential Michael acceptors,
      potential substrates for NADPH, or as photoisomerizable.

PMID- 15482914
TI  - Azaadamantane benzamide 5-HT4 agonists: gastrointestinal prokinetic SC-54750.
AB  - Azaadamantanone 1 was converted to a series of aminoazaadamantane benzamides 9a
      d, which were profiled for serotonin receptor activity. Aminomethylazaadamantane
      SC-54750 is a potent 5-HT(4) agonist and 5-HT(3) antagonist with in vivo efficacy
      in gastroparesis models and also inhibits cisplatin-induced emesis.

PMID- 15482915
TI  - Synthesis and evaluation of pyridazinylpiperazines as vanilloid receptor 1
      antagonists.
AB  - A structurally biased chemical library of pyridazinylpiperazine analogs was
      prepared in an effort to improve the pharmaceutical and pharmacological profile
      of the lead compound N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2
      yl)tetrahydropyrazine-1(2H)-carboxamide (BCTC). The library was evaluated for VR1
      antagonist activity in capsaicin-induced (CAP) and pH5.5-induced (pH) FLIPR
      assays in a human VR1-expressing HEK293 cell line. The most potent VR1
      antagonists were found to have IC(50) values in the range of 9-200nM with
      improved pharmaceutical and pharmacological profiles versus the lead BCTC. These
      compounds represent possible second-generation BCTC analogs.

PMID- 15482916
TI  - Discovery and SAR of 2-aminothiazole inhibitors of cyclin-dependent kinase 5/p25
      as a potential treatment for Alzheimer's disease.
AB  - High-throughput screening with cyclin-dependent kinase 5 (cdk5)/p25 led to the
      discovery of N-(5-isopropyl-thiazol-2-yl)isobutyramide (1). This compound is an
      equipotent inhibitor of cdk5 and cyclin-dependent kinase 2 (cdk2)/cyclin E
      (IC(50)=ca. 320nM). Parallel and directed synthesis techniques were utilized to
      explore the SAR of this series. Up to 60-fold improvements in potency at cdk5 and
      12-fold selectivity over cdk2 were achieved.

PMID- 15482917
TI  - Synthesis and antitumor activity of 4-hydroxycoumarin derivatives.
AB  - A series of 4-hydroxycoumarin derivatives was prepared and evaluated for
      antitumor activity. The key fragments were 2a-c, 5c, 12b, 13b, 17, and 18 which
      were prepared via dianion ring cyclization, Friedel-Crafts acylation, and
      Reformatsky reaction. Compound 20b showed the most potent antitumor activity
      among the total 12 derivatives and compounds 19a and 19b exhibited efficacy
      comparable to etoposide in vitro antitumor activity.

PMID- 15482918
TI  - Novel fibrinogen receptor antagonists. RGDF mimetics, derivatives of 4
      (isoindoline-5-yl)amino-4-oxobutyric acid.
AB  - The novel RGDF mimetics 9a and 9b were synthesized with the use of 4-(isoindoline
      5-yl)amino-4-oxobutyric acid as a surrogate of Arg-Gly motif. The synthesized
      compounds have demonstrated a high potency to inhibit platelet aggregation in
      vitro and to block FITC-Fg binding to alpha(IIb)beta(3) on washed human
      platelets.

PMID- 15482919
TI  - Racemic and chiral lactams as potent, selective and functionally active CCR4
      antagonists.
AB  - A series of racemic and chiral, nonracemic lactams that display high binding
      affinities, functional chemotaxis antagonism, and selectivity toward CCR4 are
      described. Compound 41, which provides reasonably high blood levels in mice when
      dosed intraperitoneally, was identified as a useful pharmacological tool to
      explore the role of CCR4 antagonism in animal models of allergic disease.

PMID- 15482921
TI  - Structurally simplified macrolactone analogues of halichondrin B.
AB  - A structurally simplified macrolactone analogue of halichondrin B was identified
      that retains the potent cell growth inhibitory activity of the natural product in
      vitro.

PMID- 15482920
TI  - Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors.
AB  - Guided by X-ray crystallography, we have extended the structure-activity
      relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B inhibitor
      (1) and more potent and equally selective (>20-fold selectivity over the highly
      homologous T-cell PTPase, TCPTP) PTP1B inhibitors were identified. Inhibitor 7
      demonstrated good cellular activity against PTP1B in COS 7 cells.

PMID- 15482922
TI  - Macrocyclic ketone analogues of halichondrin B.
AB  - Structurally simplified macrocyclic ketone analogues of halichondrin B were
      prepared by total synthesis and found to retain the potent cell growth inhibitory
      activity in vitro, stability in mouse serum, and in vivo efficacy of the natural
      product.

PMID- 15482923
TI  - An efficient approach to N-acetyl-D-glucosaminuronic acid-based sialylmimetics as
      potential sialidase inhibitors.
AB  - A novel approach to the synthesis of beta-glycosides of N-acetyl-D
      glucosaminuronic acid, in six steps and good overall yield from N-acetyl-d
      glucosamine, has been developed. The key synthetic step was the Lewis acid
      mediated O-glycosidation of methyl 1,3,4-tri-O-pivaloyl-N-acetyl-D
      glucosaminuronate (11). Elaboration of glucosaminuronides 15 and 18 provided
      novel sialylmimetics 21 and 22, which showed inhibition of Vibrio cholerae
      sialidase.

PMID- 15482924
TI  - An effective chromatographic separation of chicken red blood cell
      coproporphyrinogen oxidase and uroporphyrinogen decarboxylase, two enzymes in
      heme biosynthesis.
AB  - Of the heme biosynthetic pathway enzymes, coproporphyrinogen oxidase is one of
      the least understood. Substrate recognition studies [Prepr. Biochem.
      Biotech.1997, 27, 47, J. Org. Chem.1999, 64, 464] have been done using chicken
      blood hemolysates (CBH) as the source of this enzyme. However, the enzyme
      uroporphyrinogen decarboxylase is also present in these preparations and
      separation of these two enzymes from CBH had not yet been achieved. Thus, a
      substrate ligand column was developed by covalently linking coproporphyrin-III to
      a sepharose resin following a similar procedure previously used for the
      purification of uroporphyrinogen decarboxylase [Int. J. Biochem.1992, 24, 105].
      The ligand-resin chromatography step rapidly separates coproporphyrinogen oxidase
      from uroporphyrinogen decarboxylase as well as the majority of the hemoglobin.

PMID- 15482925
TI  - Nitroxyl (HNO) release from new functionalized N-hydroxyurea-derived acyl nitroso
      9,10-dimethylanthracene cycloadducts.
AB  - A thermal retro-Diels-Alder decomposition of N-hydroxyurea-derived acyl nitroso
      compounds and 9,10-dimethylanthracene cycloadducts followed by acyl nitroso
      compound hydrolysis produces nitrous oxide, evidence for the formation of
      nitroxyl, the one-electron reduced form of nitric oxide that has drawn
      considerable attention for its potential roles in biological systems. EPR and NMR
      spectroscopy provide further evidence for nitroxyl formation and kinetic
      information, respectively. Such compounds may prove to be useful alternative
      nitroxyl donors.

PMID- 15482926
TI  - Aryl urea analogs with broad-spectrum antibacterial activity.
AB  - The preparation and evaluation of novel aryl urea analogs as broad-spectrum
      antibacterial agents is described. Numerous compounds showed low micromolar
      minimum inhibitory concentrations (MIC) against both Gram-positive and Gram
      negative bacteria. Selected analogs also exhibited in vivo efficacy in a lethal
      murine model of bacterial septicemia.

PMID- 15482927
TI  - Nocathiacin I analogues: synthesis, in vitro and in vivo biological activity of
      novel semi-synthetic thiazolyl peptide antibiotics.
AB  - Several nocathiacin I analogues (4-35) were synthesized and evaluated for their
      antibacterial activity. Most of these semi-synthetic analogues retained very good
      in vitro and in vivo antibacterial activity of 1.

PMID- 15482928
TI  - Ketopyrrolidines and ketoazetidines as potent dipeptidyl peptidase IV (DPP IV)
      inhibitors.
AB  - In this paper, the synthesis and structure-activity relationships (SAR) of two
      classes of electrophile-based dipeptidyl peptidase IV (DPP IV) inhibitors, the
      ketopyrrolidines and ketoazetidines, is discussed. The SAR of these series
      demonstrate that the 2-thiazole, 2-benzothiazole, and 2-pyridylketones are
      optimal S1' binding groups for potency against DPP IV. In addition, both
      cyclohexyl glycine (CHG) and octahydroindole carboxylate (OIC) serve as the most
      potent S2 binding groups within each series. Stereochemistry at the alpha
      position of the central ring is relevant to potency within the ketopyrrolidines
      series, but not in the ketoazetidine series. Finally, the ketoazetidines display
      enhanced stability over the corresponding ketopyrrolidines, while maintaining
      their potency. In fact, certain stabilized ketoazetidines can maintain their in
      vitro potency and inhibit DPP IV in the plasma for up to 6h.

PMID- 15482929
TI  - Dimethoxybenzo[i]phenanthridine-12-carboxylic acid derivatives and 6H
      dibenzo[c,h][2,6]naphthyridin-5-ones with potent topoisomerase I-targeting
      activity and cytotoxicity.
AB  - The exceptional TOP1-targeting activity and antitumor activity of ARC-111, 1,
      prompted studies on similarly substituted benzo[i]phenanthridine-12-carboxylic
      ester and amide derivatives. These studies were extended to include 6-substituted
      8,9-dimethoxy-2,3-methylenedioxy-dibenzo[c,h][2,6]naphthyridin-5-ones, which
      represent reversed lactam analogues of 1. Several of these analogues retained the
      potent TOP1-targeting activity and cytotoxicity observed for ARC-111.

PMID- 15482930
TI  - Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory
      activity.
AB  - A series of compounds possessing both H(1) histamine receptor antagonist and 5
      lipoxygenase (5-LO) inhibitory activities was synthesized. The H(1)-binding
      scaffolds of cetirizine, efletirizine, and loratadine were linked to a lipophilic
      N-hydroxyurea, the 5-LO inhibiting moiety of zileuton. Both activities were
      observed in vivo, as was increased CYP3A4 inhibition compared to their respective
      single-function drugs. Selected analogs in the series were shown to be orally
      active in guinea pig models.

PMID- 15482931
TI  - Synthesis and HIV-1 integrase inhibitory activity of dimeric and tetrameric
      analogs of indolicidin.
AB  - We found that indolicidin, a natural antimicrobial peptide, has HIV-1 integrase
      inhibitory activity. Subsequently, we also discovered analogs of indolicidin with
      substantially higher inhibitory potency. The dimers and tetramers of the most
      active sequence (ILPWKWPWWPWPP) were prepared by connection of the monomers' C
      terminal ends, using lysine as a linker. The inhibitory potency of the dimeric
      peptide is higher than the monomeric peptide. The tetrameric peptide, prepared by
      connection of two dimers at C-ends using again lysine as the linker, is the most
      potent integrase inhibitor with IC(50) value of 0.6 microM for both 3'-end
      processing and strand transfer.

PMID- 15482932
TI  - Identification of neutral 4-O-alkyl quinolone nonpeptide GnRH receptor
      antagonists.
AB  - A series of neutral, nonbasic quinolone GnRH antagonists were prepared via
      Mitsunobu alkylation of protected and unprotected 4-hydroxy quinolone
      intermediates. The synthetic route was improved by utilization of unique
      reactivity and convergency afforded by the use of mono and bis
      trimethylsilylethyl protected quinolones. Potent neutral GnRH antagonists were
      identified, including ether and lactam derivatives, that show similar in vitro
      binding affinity and functional activity as compared to the earlier basic 4
      aminoalkyl quinolone series of nonpeptide GnRH antagonists.

PMID- 15482933
TI  - Piperazinebenzylamines as potent and selective antagonists of the human
      melanocortin-4 receptor.
AB  - SAR studies of a series of piperazinebenzylamines resulted in the discovery of
      potent antagonists of the human melanocortin-4 receptor. Compounds 11c, 11d, and
      11l, which had K(i) values of 21, 14, and 15 nM, respectively, possessed low
      efficacy in cAMP stimulation ( approximately 15% of alpha-MSH maximal level)
      mediated by MC4R, and functioned as antagonists in inhibition of alpha-MSH
      stimulated cAMP release in a dose-dependent manner (11l, IC(50)=36 nM).

PMID- 15482934
TI  - QSAR modeling of the MAO inhibitory activity of xanthones derivatives.
AB  - This work presents a study QSAR among the MAO A inhibitory activity (IMAO A) of a
      xanthones series correlated with descriptors like the E-state index (S(i)),
      molecular connectivity (chi) and shape (k) descriptors. The xanthones group (9-H
      xanton-9-onas) are of natural or synthetic origin, they present eight positions
      for the substitution and their MAO A inhibitory activity is reported in the work
      from Gnerre et al. The descriptors included in the adjusted model were selected
      to describe the molecular structure of the compounds. The model was selected
      using the leave-one-out method, the cross-validation statistics indicate a model
      useful for prediction: r(2)=0.847 and s=8.069, calculated by multiple linear
      regression.

PMID- 15482935
TI  - Synthesis of 61-bis(1-adamantylcarbamoyl)-1,2-methano[60]fullerene and its
      antagonistic effect on haloperidol-induced catalepsy in mice.
AB  - The 61-bis(1-adamantylcarbamoyl)-1,2-methano[60]fullerene was synthesized from
      N,N'-di(1-adamantyl)malondiamide and C(60) in the presence of 1,8
      diazabicyclo[5,4,0]-7-undecene. The intraperitoneal administration of this
      fullerene derivative (10mg/kg) caused an antagonistic effect on haloperidol
      induced catalepsy in mice.

PMID- 15482936
TI  - Antioxidant activities of a new lignan and a neolignan from Saururus chinensis.
AB  - A new diarylbutane lignan, 2'-hydroxy dihydroguaiaretic acid (4), and a known 8-O
      4'-type neolignan, machilin D (5), were isolated from the ethyl acetate extracts
      of the underground parts of Saururus chinensis. Compounds 4 and 5 exhibited low
      density lipoprotein (LDL)-antioxidant activity in the thiobarbituric acid
      reactive substances (TBARS) assay (4: IC(50)=3.3 microM and 5: IC(50)=3.8
      microM), the lag time of conjugated diene production, the relative
      electrophoretic mobility (REM) of ox-LDL, the apoB-100 fragmentation on copper
      mediated LDL oxidation and the macrophage-mediated LDL oxidation, and radical
      DPPH scavenging activity.

PMID- 15482937
TI  - Quantitative structure-activity relationship analyses of antioxidant and free
      radical scavenging activities for hydroxybenzalacetones.
AB  - Antioxidant activities for a series of hydroxybenzalacetones, OH-BZ, were
      evaluated by measuring inhibitory potencies of OH-BZ against lipid peroxidation
      induced by t-BuOOH or gamma-irradiation. Their quantitative structure-activity
      relationship (QSAR) studies indicated that the activities are mainly governed by
      electronic and steric factors. To rationalize these results, we also performed
      QSAR analyses for DPPH radical scavenging activities of OH-BZ, which indicated
      that antioxidant and radical scavenging activities could be expressed by the same
      physicochemical parameters but the hydrogen bonding behavior of phenolic OH
      varies with the reaction medium.

PMID- 15482938
TI  - Synthesis and amine transporter affinities of novel phenyltropane derivatives as
      potential positron emission tomography (PET) imaging agents.
AB  - A series of novel fluoroalkyl-containing tropane derivatives (6-8, 10-14, 17, and
      18) were synthesized from cocaine. Novel compounds were evaluated for affinity
      and selectivity in competitive radioligand binding assays selective for cerebral
      serotonin (5-HT), dopamine (DA), and norepinephrine (NE) transporters (SERT, DAT,
      and NET). The nortropane-fluoroalkyl esters (7, 10, 11) were most potent for SERT
      (K(i): 0.18, 0.24, and 0.30 nM, respectively). Tosylate esters 17 and 18,
      synthesized as precursors for [(18)F]-labeled, Positron Emission Tomography (PET)
      imaging agents, also showed high affinity for DAT.

PMID- 15482939
TI  - Synthesis of 5'-substituted fluoro-neplanocin A analogues: importance of a
      hydrogen bonding donor at 5'-position for the inhibitory activity of S
      adenosylhomocysteine hydrolase.
AB  - Four 5'-substituted fluoro-neplanocin A analogues 1a-d were designed and
      synthesized, using cyclopentenone derivative 2 as a key intermediate. The
      inhibitory activity against SAH was in the following order: NH(2)>SH>F, N(3),
      indicating a hydrogen bonding donor such as OH or NH(2) was essential for
      inhibitory activity. All the final compounds showed much less decreased
      cytotoxicity in two cancer cell lines (Col2 and A549), implying that
      phosphorylation of the 5'-hydroxyl group of fluoro-neplanocin A is closely
      related to its high cytotoxicity.

PMID- 15482940
TI  - Identification and structure-activity relationship studies of 3-methylene-2
      norbornanone as potent anti-proliferative agents presumably working through p53
      mediated apoptosis.
AB  - We have identified a novel series of alpha-methylene carbonyl compounds through
      structure-activity relationship (SAR) studies with high levels of anti
      proliferative activities. The lead molecule, 3-methylene-2-norbornanone (3)
      showed potent activity (LC(50)=3-8 microM) against mutant p53 cell types and many
      fold selectivity (>13-29) over wild-type p53 cells. Further, compound 3 and its
      analogs showed refolding of mutant p53 protein comparable to their anti
      proliferative activities suggesting possible interaction with mutant p53 protein.

PMID- 15482941
TI  - Synthesis and CYP24 inhibitory activity of 2-substituted-3,4-dihydro-2H
      naphthalen-1-one (tetralone) derivatives.
AB  - The synthesis of novel 2-benzyl- and 2-benzylidene-3,4-dihydro-2H-naphthalen-1
      one (tetralone) derivatives and their inhibitory activity versus kidney
      mitochondrial 25-hydroxyvitamin D(3) 24-hydroxylase (CYP24) is described. The 2
      benzylidenetetralone derivatives were found to be very weak inhibitors (IC(50) 20
      >100 microM), whereas the 2-benzyltetralone derivatives showed promising
      inhibitory activity (IC(50) 0.9 microM for the most active derivative) compared
      with ketoconazole (IC(50) 20 microM).

PMID- 15482942
TI  - Proposal of new modification technique for linear double-stranded DNAs using the
      polysaccharide schizopyllan.
AB  - A natural polysaccharide schizophyllan (SPG) has been known to form a stable
      complex with poly(dA). We attached a poly(dA)(80) tail to the both ends of a
      linear double-stranded DNA, which had been prepared from a plasmid DNA vector.
      The poly(dA) tailed DNA verified to form complex with SPG by gel electrophoresis
      and atomic force microscopy (AFM). AFM images indicated that the complexes
      exhibit a dumbbell-like architecture, that is, quite similar to that of
      adenovirus genome. The complex demonstrated excellent exonuclease resistance,
      probably because of the protection effect by SPG complexation.

PMID- 15482943
TI  - Topological modeling of lipophilicity, diuretic activity, and carbonic inhibition
      activity of benzene sulfonamides: a molecular connectivity approach.
AB  - A large series of distance-based topological indices has been used for modeling
      lipophilicity, diuretic activity, and carbonic anhydrase inhibition activity of a
      library of simple substituted benzene sulfonamides. The results have shown that
      the topological approach used is quite useful for modeling carbonic anhydrase
      inhibition and the use of molecular connectivity is the best for this purpose.
      Excellent results are obtained in multiparametric regressions. The results are
      critically discussed on the basis of statistical parameters.

PMID- 15482944
TI  - Myxopyronin B analogs as inhibitors of RNA polymerase, synthesis and biological
      evaluation.
AB  - A series of myxopyronin B analogs has been prepared via a convergent synthetic
      route and were tested for in vitro inhibitory activity against DNA-dependent RNA
      polymerase and antibacterial activity against E. coli and S. aureus. The parent
      lead compound proved to be very sensitive to even small changes. Only the achiral
      desmethyl myxopyronin B (1a) provided enhanced potency.

PMID- 15482945
TI  - Preparation of a tritiated ginkgolide.
AB  - Ginkgolide B, a constituent of the tree Ginkgo biloba, was radiolabeled with the
      beta-emitter tritium ([(3)H]) in two steps from ginkgolide C. First, a triflate
      precursor was prepared utilizing the selective reactivity of 7-OH in ginkgolide
      C; the triflate was then reduced with sodium borotritide to yield tritiated
      ginkgolide B ([(3)H]GB) in good yield and high specific activity. The tritiated
      ginkgolide will be an important tool for studying neuromodulatory properties of
      ginkgolides.

PMID- 15482946
TI  - Intact glycation end products containing carboxymethyl-lysine and glyoxal lysine
      dimer obtained from synthetic collagen model peptide.
AB  - Advanced glycation end products (AGE) are accumulated in human tissues when long
      lived proteins are glycated due to hyperglycemia and/or aging. In this study, we
      synthesized a collagen model peptide, Ac-(Pro-Hyp-Gly)(5)-Pro-Lys-Gly-(Pro-Hyp
      Gly)(5)-Ala-NH(2) to investigate intact AGEs in peptides. The peptide formed a
      stable triple helix structure, and was subjected to glycation reactions with
      glucose, ribose and glyoxal. Besides carboxymethyl-lysine in the peptide, a
      conjugated form linked with glyoxal lysine dimer (GOLD) was detected upon
      treatment with glyoxal. This is the first example of intact glycation-derived
      dimers of peptides retaining intrinsic protein structures.

PMID- 15482947
TI  - Pyrazolo[1,5-a]pyrimidines as estrogen receptor ligands: defining the orientation
      of a novel heterocyclic core.
AB  - We have examined the pyrazolo[1,5-a]pyrimidine scaffold as a novel core structure
      for estrogen receptor ligands. Attachment of various substituents has helped to
      define the orientation of this heterocycle in the ligand-binding pocket as one in
      which a pendant phenol rather than the hydroxylpyrimidine serves as a mimic of
      the A-ring of estradiol.

PMID- 15482948
TI  - Potent inhibitors of the HIV-1 protease incorporating cyclic urea P1-P2 scaffold.
AB  - We have developed synthetic approaches to novel analogues of 2-imidazolidinone
      scaffold 2, which was found to be an effective P1-P2 mimetic in HIV-1 protease
      inhibitor 4. This enabled a rapid synthesis of analogues of 4 and subsequently
      allowed us to evaluate and rationalize the SAR. Accordingly, trans relationship
      of P1 and P2 substituents in the P1-P2 mimetic, as found in a related 2
      pyrrolidone-based scaffold 1, was found necessary for high potency against HIV-1
      protease. Results of this study provided further rationale towards subsequent
      optimization of 2-pyrrolidone-based lead 3, which led us to potent and drug-like
      HIV-1 protease inhibitors described in a follow-on report (Bioorg. Med. Chem.
      Lett. 2004, 14, in press. ).

PMID- 15482949
TI  - Discovery of potent pyrrolidone-based HIV-1 protease inhibitors with enhanced
      drug-like properties.
AB  - We have developed efficient syntheses of the HIV-1 protease inhibitor 4 and its
      analogues, which incorporate the pyrrolidone scaffold 2 as P1-P2 moiety.
      Evaluation of these analogues in the HIV-1 protease enzyme assay resulted in
      discovery of potent and more water soluble meta-amino- and meta-hydroxy
      inhibitors 17b and 19b. The SAR observed in this class of PIs could be
      rationalized with aid of the X-ray structure of inhibitor 28 co-crystallized with
      the HIV-1 protease, which suggested that the polar meta- (but not para-) benzyl
      substituents in P2 could side-step the hydrophobic S2 enzyme active pocket by
      rotating the P2 moiety around its Cbeta-Cgamma bond. Such reorientation allows to
      engage the unsubstituted, hydrophobic edge of benzyl moiety in P2 in the
      requisite P2/S2 hydrophobic interaction, and projects polar meta-substituent into
      the bound water. It appears that the meta-position can be chemically derivatized
      without potency loss of thus resulting inhibitors, as evidenced by potent 22-26.
      We thus identified pyrrolidone 2-based inhibitors exemplified by 17b and 19b,
      which uniquely accommodate both high enzyme potency and which provide a platform
      for fine-tuning of drug-like properties in this class of PIs by additional
      chemical manipulations on the meta-position.

PMID- 15482950
TI  - Azepinone as a conformational constraint in the design of kappa-opioid receptor
      agonists.
AB  - A new class of kappa-opioid receptor agonists is described. The design of these
      agents was based upon energy minimization and structural overlay studies of the
      generic azepin-2-one structure 3 with the crystal structure of arylacetamide
      kappa agonist 1, ICI 199441. The most active compound identified was ligand 4a
      (K(i)=0.34 nM), which demonstrated potent antinociceptive activity after oral
      administration in rodents.

PMID- 15482951
TI  - Synthesis of fluorinated analogues of SJG-136 and their DNA-binding potential.
AB  - A series of C2-exo-fluorounsaturated pyrrolobenzodiazepines (PBDs) have been
      synthesized. These C2-exo-fluorounsaturated PBD dimers have exhibited remarkable
      DNA-binding affinity.

PMID- 15482952
TI  - Carbonic anhydrase inhibitors: inhibition of human cytosolic isozyme II and
      mitochondrial isozyme V with a series of benzene sulfonamide derivatives.
AB  - Among the 14 human isozymes of carbonic anhydrase (CA, EC 4.2.1.1) presently
      known, the cytosolic hCA II is the most active and plays a host of physiological
      functions, whereas the mitochondrial hCA V is unique due to its role in several
      biosynthetic reactions. An inhibition study of these isozymes with a series of
      sulfonamides is reported here, with the scope to detect lead molecules for the
      design of isozyme-specific CA inhibitors (CAIs) targeting the mitochondrial
      isoform. Indeed, recently it has been shown that CA V is a novel target for the
      drug design of anti-obesity agents among others. Compounds included in this study
      were mainly ortho-, meta-, and para-substituted-benzenesulfonamides, together
      with several halogeno-substituted sulfanilamides and disubstituted-benzene-1,3
      disulfonamide derivatives. Isozyme V showed an inhibition profile with these
      sulfonamides different of that of hCA II. Thus, IC(50) values in the range of 80
      nM to 74 microM against hCA II, and 0.78-63.7 microM against hCA V with these
      derivatives have been obtained. Only one compound, 2-carboxymethyl
      benzenesulfonamide, was more active against hCA V over hCA II (selectivity ratio
      of 1.39), whereas all other derivatives investigated here were much better hCA II
      inhibitors (selectivity ratios CA II/CA V in the range of 0.0008-0.73) than hCA V
      inhibitors.

PMID- 15482953
TI  - Synthesis, radiolabeling, and preliminary biological evaluation of [3H]-1-[(S)
      N,O-bis-(isoquinolinesulfonyl)-N-methyl-tyrosyl]-4-(o-tolyl)-piperazine, a potent
      antagonist radioligand for the P2X7 receptor.
AB  - The design, synthesis, and preliminary biological evaluation of the first potent
      radioligand antagonist for the P2X(7) receptor, named [(3)H]-1-[(S)-N,O-bis
      (isoquinolinesulfonyl)-N-methyl-tyrosyl]-4-(o-tolyl)-piperazine (compound 13),
      are reported. This compound bound to human P2X(7) receptors expressed in HEK
      transfected cells with K(D) and B(max) value of 3.46+/-0.1 nM and 727+/-73
      fmol/mg of protein, respectively. The high affinity and facile labeling makes it
      a promising radioligand for a further characterization of P2X(7) receptor
      subtype.

PMID- 15482954
TI  - Further evidence of genetic heterogeneity in autosomal dominant distal motor
      neuronopathy.
AB  - Distal hereditary motor neuronopathy is a genetically and clinically
      heterogeneous disorder. To date, five loci, and their relative genes, have been
      mapped on chromosomes 7p14, 7q11, 9q34, 11q12 and 12q24, respectively. We
      describe an Italian family with autosomal dominant distal HMN starting at around
      30 years of age with weakness and atrophy of distal leg muscles and pyramidal
      features. We performed genetic linkage analysis on chromosomes 7p14, 9q34, 11q12
      and 12q24. Moreover we sequenced the genes mapped to 7q11 and 12q24. Negative LOD
      scores excluded linkage to 7p14, 9q34, and 11q12 chromosomes in our family. No
      mutations were found in genes mapped to 7q11 and 12q24. In addition, because of
      pyramidal features, we performed the linkage analysis to all the known loci for
      autosomal dominant hereditary spastic paraparesis. The analysis was negative thus
      excluding a complicated form of autosomal dominant hereditary spastic
      paraparesis. These data further confirm a genetic heterogeneity within inherited
      motor neuronopathy.

PMID- 15482955
TI  - Expression profiling in spinal muscular atrophy reveals an RNA binding protein
      deficit.
AB  - Spinal muscular atrophy is a common neuromuscular disorder caused by deletions or
      mutations within the survival motor neuron gene. The reason for specific motor
      neuron loss within the disease is still unclear. Expression profiling has been
      carried out in two models of spinal muscular atrophy; the heterozygote mouse
      model and human primary muscle cultures from a spinal muscular atrophy patient. A
      group of RNA binding proteins are up-regulated in spinal muscular atrophy motor
      neurons. One such protein, BRUNOL3, is highly expressed within spinal cord and
      muscle and also at the same developmental stage as survival motor neuron. The
      differential expression of Brunol3 has been confirmed with real-time RT-PCR in
      spinal cord and muscle of three different models of spinal muscular atrophy.
      BRUNOL3 has been shown to co-localise with survival motor neuron in the nuclei of
      neuronal cells and to co-immunoprecipitate with Smn in mouse brain. This is the
      first time that a link has been established between RNA binding proteins and
      survival motor neuron within motor neurons.

PMID- 15482956
TI  - Monomelic amyotrophy associated with the 7472insC mutation in the mtDNA
      tRNASer(UCN) gene.
AB  - We describe a 49-year-old male patient who experienced progressive amyotrophy
      with no sensorial abnormality in the left arm since 45 years of age. The
      neuromuscular syndrome was identical to that known as Hirayama disease, a rare
      form of focal lower motor neuron disease affecting the C7-C8-T1 metamers of the
      spinal cord. Asymmetric neurosensorial hearing loss was present since age 35 in
      the patient, and was also documented in an elder sister and in the mother. A
      muscle biopsy showed cytochrome c oxidase (COX) negative fibers but no ragged-red
      fibers, and mild reduction of COX was confirmed biochemically. The patient was
      found to have high levels of a known pathogenic mutation of mtDNA, the 7472insC
      in the gene encoding the tRNA(Ser(UCN)). Investigation on several family members
      showed a correlation between mutation load and clinical severity. This is the
      second report documenting the association of lower motor neurone involvement with
      a specific mtDNA.

PMID- 15482957
TI  - Mutation screening in Korean hypokalemic periodic paralysis patients: a novel
      SCN4A Arg672Cys mutation.
AB  - Familial hypokalemic periodic paralysis is an autosomal-dominant disorder with
      features of both genetic and phenotypic heterogeneity. Mutation screening was
      performed on Korean hypokalemic periodic paralysis patients to locate the
      corresponding mutations and to specify the clinical features associated with the
      mutations. Target-exon PCR, direct sequencing, and restriction fragment length
      polymorphism analysis were used. A novel SCN4A Arg672Cys mutation and a known
      CACNL1A3 Arg528His mutation were identified. Incomplete penetrance in women with
      Arg672Cys mutation was evident. A comparison of the present study with previous
      studies raises the possibility that hypokalemic periodic paralysis is an allelic
      specific or mulfactorial, rather than a gene-specific, disorder. Reported herein
      are two Korean hypokalemic periodic paralysis families, one carrying a novel
      SCN4A Arg672Cys mutation with incomplete penetrance in women, and the other
      carrying a CACNL1A3 Arg528His mutation, with the onset of characteristics of
      hypoPP developing at an earlier age, as well as a higher penetrance rate in
      women.

PMID- 15482958
TI  - Characteristics of the increase in plasma brain natriuretic peptide level in left
      ventricular systolic dysfunction, associated with muscular dystrophy in
      comparison with idiopathic dilated cardiomyopathy.
AB  - To determine whether the plasma brain natriuretic peptide level increases
      differentially in muscular dystrophy and idiopathic dilated cardiomyopathy, we
      investigated the plasma brain natriuretic peptide level and echocardiographic
      parameters in patients with similarly low left ventricular ejection fraction. The
      plasma brain natriuretic peptide level was lower, and the left ventricular end
      diastolic diameter was shorter in the patients with muscular dystrophy than in
      those with idiopathic dilated cardiomyopathy. The correlation between the plasma
      brain natriuretic peptide and left ventricular ejection fraction was shifted
      downward in the patients with muscular dystrophy compared with those with
      idiopathic dilated cardiomyopathy. Those between the brain natriuretic peptide
      and left ventricular end-diastolic diameter were superimposable, although the
      data from the muscular dystrophy patients were located at the shorter left
      ventricular end-diastolic diameter side. The plasma brain natriuretic peptide
      level may differentially increase in the two diseases with similar left
      ventricular systolic dysfunction. Differences in the left ventricular distension
      and in the physical activity might explain at least partially the different
      plasma brain natriuretic peptide levels.

PMID- 15482960
TI  - A newly identified chromosomal microdeletion of the rapsyn gene causes a
      congenital myasthenic syndrome.
AB  - The objective is mutation analysis of the RAPSN gene in a patient with sporadic
      congenital myasthenic syndrome (CMS). Mutations in various genes encoding
      proteins expressed at the neuromuscular junction may cause CMS. Most mutations
      affect the epsilon subunit gene of the acetylcholine receptor (AChR) leading to
      endplate AChR deficiency. Recently, mutations in the RAPSN gene have been
      identified in several CMS patients with AChR deficiency. In most patients, RAPSN
      N88K was identified, either homozygously or heteroallelic to a second missense
      mutation. A sporadic CMS patient from Germany was analyzed for RAPSN mutations by
      RFLP, long-range PCR and sequence analysis. Clinically, the patient presents with
      an early onset CMS, associated with arthrogryposis multiplex congenita, recurrent
      episodes of respiratory insufficiency provoked by infections, and a moderate
      general weakness, responsive to anticholinesterase treatment. The mutation RAPSN
      N88K was found heterozygously to a large deletion of about 4.5 kb disrupting the
      RAPSN gene. Interestingly, an Alu-mediated unequal homologous recombination may
      have caused the deletion. We hypothesize that numerous interspersed Alu elements
      may predispose the RAPSN locus for genetic rearrangements.

PMID- 15482959
TI  - Myositis in infiltrative lymphocytosis syndrome: clinicopathological observations
      and treatment.
AB  - Diffuse infiltrative lymphocytosis syndrome (DILS) is characterized by the
      presence of persistent circulating CD8 lymphocytosis and visceral CD8 lymphocytic
      infiltration, predominantly in the salivary glands and lungs in a subset of human
      immunodeficiency virus (HIV) patients. Myositis has been rarely documented in
      DILS. We report here the histopathological abnormalities and treatment response
      of an HIV patient with DILS associated myositis. Muscle biopsy revealed features
      of polymyositis but electron microscopy study showed intranuclear filamentous
      inclusions of 18 nm diameter, without intracytoplasmic inclusion. Treatment with
      intravenous immunoglobuline was useful.

PMID- 15482961
TI  - Two novel mutations in the spastin gene (SPG4) found by DHPLC mutation analysis.
AB  - The most common form of autosomal dominant hereditary spastic paraplegia is
      caused by mutations in the gene encoding spastin (SPG4), a member of the AAA
      family of ATPases. In the current study, we designed a denaturing high
      performance liquid chromatography based protocol for the analysis of the SPG4
      gene. Using this method, we detected two novel missense mutations, 1375A > G
      (R459G) and 1378C > T (R460C), one previously described five bases deletion
      (1215_1219del) and three polymorphic changes. This study suggests that denaturing
      high-performance liquid chromatography would be a fast and reliable tool in the
      investigation of the molecular defects in the SPG4 gene.

PMID- 15482962
TI  - 111th ENMC International Workshop on Multi-minicore Disease. 2nd International
      MmD Workshop, 9-11 November 2002, Naarden, The Netherlands.

PMID- 15482963
TI  - 121st ENMC International Workshop on Desmin and Protein Aggregate Myopathies. 7-9
      November 2003, Naarden, The Netherlands.

PMID- 15482964
TI  - Emergency contraception: do we have the political will to increase access?

PMID- 15482965
TI  - Physical violence against impoverished women: a longitudinal analysis of risk and
      protective factors.
AB  - Violence represents a significant threat to the health of impoverished women. Few
      studies have examined what characteristics might be associated with increased
      risk of violence or protection from physical violence directed at such women,
      although this information is important in informing violence prevention and
      intervention efforts. This is the first study to our knowledge that has
      prospectively examined, in representative probability samples of impoverished
      women, multiple risk and protective factors to understand their relative
      importance to physical victimization. Study participants were 810 women in Los
      Angeles County, 402 in shelters and 408 in Section 8 low-income housing, who
      completed structured interviews at baseline and 6-month follow-up. Significant (p
      < .05) multivariate predictors of physical violence experienced during the 6
      months prior to follow-up interview were physical or sexual violence experienced
      as a child, physical violence experienced during the 6 months prior to baseline
      interview, having multiple sexual partners, psychological distress, and poor
      social support. Results of this study highlight the persistence of physical
      violence in the lives of impoverished women and plausible, prospective risk
      factors for this violence. Findings also highlight opportunities to reduce
      women's risk of experiencing violence through enhancing women's social support
      and mental health.

PMID- 15482966
TI  - Correlates of body mass index and waist-to-hip ratio among Mexican women in the
      United States: implications for intervention development.
AB  - INTRODUCTION: This study contributes to our understanding of acculturation and
      obesity by examining the association between several measures of acculturation,
      including a bidimensional scale of acculturation, body mass index (BMI), and
      waist-to-hip ratio (WHR). METHODS: Exploratory analyses were performed using
      baseline data from 357 Mexican women recruited into a Spanish-language randomized
      community trial. The women were randomly sampled by telephone and interviewed in
      their homes. Women's height, weight, waist, and hip were measured to obtain
      estimates of their BMI and WHR. A face-to-face interview collected data on
      dietary intake, physical activity, acculturation, and other demographic and
      psychosocial variables. RESULTS: Less than a quarter of the women were normal
      weight (39% overweight and 41% obese). Univariate analyses revealed that more
      years living in the United States and less integration into the Anglo culture
      were associated with a larger BMI and WHR. However, in the multivariate analyses,
      significant correlates of a larger BMI were less moderate physical activity and
      unemployment. There were trends linking a larger BMI with older age, no vigorous
      physical activity, more energy intake, and less integration into the Anglo
      culture. These same variables plus less household income were associated with a
      higher WHR. Exploratory analyses on acculturation revealed that bicultural
      Mexican-American women were more educated, more likely to be employed, reported a
      higher household income, and perceived fewer barriers to a healthy diet compared
      with traditional Mexican women. CONCLUSIONS: Intervention designed to prevent
      overweight/obesity should consider promoting maintenance of Mexican cultural
      practices, as well as teach women how to effectively integrate into the Anglo
      culture.

PMID- 15482967
TI  - The use of complementary and alternative medications by menopausal women in South
      East Queensland.
AB  - This study aimed to identify the prevalence and types of complementary and
      alternative medications (CAMs) used by women during menopause and explore
      potential associations between CAM use and menopausal symptoms. Analysis was
      undertaken with 886 randomly selected menopausal women aged 47-67 years who
      participated in a postal questionnaire on the menopause experience. The
      prevalence of CAM use was relatively high (82.5%), with nutrition most commonly
      cited (67%), followed by phytoestrogens (56%), herbal therapies (41%), and CAM
      medications (25%). Multivariate analysis adjusted for confounders revealed that
      women who consumed CAM medications were 17-23% more likely to report anxiety (p =
      .019) or vasomotor symptoms (p = .013). Women who used herbal therapies (p =
      .009) or phytoestrogens (p = .030) were 13-16% more likely to experience
      vasomotor symptoms. Women who used nutrition were 18% more likely to experience
      anxiety (p = .049). These results highlight the importance for health
      professionals to incorporate CAMs into their practice to better inform menopausal
      women of their treatment choices.

PMID- 15482968
TI  - New teen drivers and their parents: what they know and what they expect.
AB  - OBJECTIVES: To assess teens' and parents' knowledge of teen driver safety and to
      compare teens' and parents' expectations about learning to drive and acquiring a
      driver's license. METHODS: A convenience sample of 613 Connecticut teens enrolled
      in commercial driving schools and one of their parents completed self
      administered surveys. RESULTS: Significant differences between teens and parent
      expectations were noted in practice driving with a parent, driving to approved
      destinations, unlimited vehicle access, curfew, and teen passenger limits.
      CONCLUSIONS: The discrepancy between teens' and parents' expectations indicates
      the need to persuade and empower parents to manage their teen's driving
      experience more rigorously.

PMID- 15482969
TI  - Neighborhood, family, and child predictors of childhood injury in Canada.
AB  - OBJECTIVE: To examine independent and combined effects of child, family and
      neighborhood on medically attended childhood injuries. METHODS: Logistic modeling
      of longitudinal data (n=9796) from the Census Linked National Longitudinal Survey
      of Children and Youth. RESULTS: Child age and gender were strong predictors of
      injuries. Smaller effects were found for parenting, neighborhood cohesion among
      difficult children less than 2 years old, and neighborhood disadvantage among
      aggressive children 2-3 years old. CONCLUSION: Neighborhood in addition to
      parenting can affect injury risk. Further research is needed into the influence
      of neighborhood disadvantage and the processes of neighbor's cohesion at
      different childhood stages.

PMID- 15482970
TI  - Correlates of fat intake among urban, low income African Americans.
AB  - OBJECTIVE: To test a dietary intervention for high risk African American adults
      with small children. METHODS: Using telephone data, logistic regression was used
      to identify association of low-fat eating behaviors, fat calories, and frequency
      of sweets/oils/fats with personal and environmental variables. RESULTS: Education
      and income were associated with low-fat eating behaviors, fat calories, and
      frequency of fat/oils/sweets. Availability, price, and policy were related to low
      fat eating behaviors. CONCLUSIONS: Effectiveness of dietary interventions relies
      upon environments that support changes by the individual. Focusing on high-risk
      populations should be a priority in this research.

PMID- 15482971
TI  - Attitudes of young african american fathers toward early childbearing.
AB  - OBJECTIVE: To qualitatively examine the perceptions of young fathers toward
      issues related to early childbearing. METHODS: Focus groups were held with male
      partners of adolescent females who had become pregnant while participating in an
      HIV-prevention trial. RESULTS: Primary domains that emerged included young male's
      desire for pregnancy, their attitudes toward father/child involvement, and their
      perceived social support as young fathers. CONCLUSIONS: Findings may help in
      developing gender-appropriate interventions to delay early childbearing and
      prevent HIV/STD transmission.

PMID- 15482972
TI  - Comparison of social variables for understanding physical activity in adolescent
      girls.
AB  - OBJECTIVE: To evaluate social support and theory of planned behavior (TPB)
      constructs in explaining physical activity in adolescent girls. METHODS: One
      thousand seven hundred ninety-seven 8th-grade girls completed a survey measuring
      social provisions, family support, TPB constructs, moderate-to-vigorous physical
      activity (MVPA), and team sport involvement (TSI). RESULTS: Structural equation
      modeling (SEM) indicated statistically significant direct effects from TPB
      constructs and social provisions to intention; social provisions, family support,
      and intention to MVPA; and social provisions and family support to TSI.
      CONCLUSIONS: Social variables play a greater role in explaining TSI than in
      explaining MVPA in this sample.

PMID- 15482973
TI  - Validity of the body mass index silhouette matching test.
AB  - OBJECTIVE: To determine the construct validity and utility of the Body Mass Index
      Silhouette Matching Test (BMI-SMT). METHODS: One-hundred-seventy undergraduate
      students at a mid-Atlantic university completed the BMI-SMT, the Gardner 2-figure
      Silhouette Matching Test and were measured for height and weight. RESULTS:
      Validity coefficients using Pearson r correlations ranged from 0.69 to 0.84 for
      comparisons between BMI values for the BMI-SMT, and the GSMT and actual BMI
      measures. Coefficients for weight values produced r-values ranging from 0.59 to
      0.84. Analysis of the BMI-SMT ability to accurately assess weight classification
      indicated a tendency toward overestimation. CONCLUSION: The BMI-SMT is a valid
      measure of body image perceptions and estimates of weight and BMI.

PMID- 15482974
TI  - Effects of social support at work on depression and organizational productivity.
AB  - OBJECTIVE: To examine how social support at work affects depression and
      organizational productivity in a work-stress framework. METHODS: A self
      administered survey for 240 workers in a public hospital in the southeastern
      United States. RESULTS: Social support at work was directly related to high job
      control, low depression, and high job performance. Social support did not buffer
      the negative effects of work factors on depression and organizational
      productivity. CONCLUSIONS: Social support at work had a direct and beneficial
      effect on workers' psychological well-being and organizational productivity
      without any interaction effect on the work-stress framework.

PMID- 15482975
TI  - Bupropion SR for relapse prevention: a "slips-allowed" analysis.
AB  - OBJECTIVE: To assess the efficacy of bupropion SR on smoking abstinence using a
      "slips allowed" analysis. METHODS: Retrospective analysis, which did not consider
      brief episodic "slips" as a return to regular smoking, of data from a
      multicenter, randomized, doubleblind, placebo-controlled relapse prevention
      study. RESULTS: Using a slips-allowed analysis, median time to relapse on
      bupropion SR was 65 weeks versus 30 weeks on placebo. This is compared to 32 and
      20 weeks, respectively, using a traditional analysis not allowing for slips.
      CONCLUSION: Bupropion SR is efficacious for the prevention of smoking relapse. A
      slips-allowed analysis may provide a more clinically relevant assessment of
      efficacy.

PMID- 15482976
TI  - Prevalence of CVD risk factors among adults with diabetes by mental distress
      status.
AB  - OBJECTIVE: To determine whether mental distress among diabetic persons is
      associated with various CVD risk factors. METHODS: Behavioral Risk Factors
      Surveillance System, an ongoing, statebased, random-digit-dialed telephone survey
      of the noninstitutionalized US adult population. RESULTS: Diabetic persons with
      mental distress were more likely than those without mental distress to smoke to
      have hypercholesterolemia and hypertension and not to engage in leisure-time
      physical activity. CONCLUSIONS: Mental health professionals need to be involved
      in the care of diabetic persons so they can recognize and treat symptoms of
      mental distress and participate in research to identify interventions that can
      reduce mental distress and reinforce healthy behaviors.

PMID- 15482979
TI  - Raman spectroscopy of graphite.
AB  - We present a review of the Raman spectra of graphite from an experimental and
      theoretical point of view. The disorder-induced Raman bands in this material have
      been a puzzling Raman problem for almost 30 years. Double-resonant Raman
      scattering explains their origin as well as the excitation-energy dependence, the
      overtone spectrum and the difference between Stokes and anti-Stokes scattering.
      We develop the symmetry-imposed selection rules for double-resonant Raman
      scattering in graphite and point out misassignments in previously published
      works. An excellent agreement is found between the graphite phonon dispersion
      from double-resonant Raman scattering and other experimental methods.

PMID- 15482980
TI  - Raman scattering of non-planar graphite: arched edges, polyhedral crystals,
      whiskers and cones.
AB  - Planar graphite has been extensively studied by Raman scattering for years. A
      comparative Raman study of several different and less common non-planar graphitic
      materials is given here. New kinds of graphite whiskers and tubular graphite
      cones (synthetic and natural) have been introduced. Raman spectroscopy has been
      applied to the characterization of natural graphite crystal edge planes, an
      individual graphite whisker, graphite polyhedral crystals and tubular graphite
      cones. Almost all of the observed Raman modes were assigned according to the
      selection rules and the double-resonance Raman mechanism. The polarization
      properties related to the structural features, the line shape of the first-order
      dispersive mode and its combination modes, the frequency variation of some modes
      in different carbon materials and other unique Raman spectral features are
      discussed here in detail.

PMID- 15482981
TI  - Determination of nanotubes properties by Raman spectroscopy.
AB  - The basic concepts and characteristics of Raman spectra from single-wall carbon
      nanotubes (SWNTs, both isolated and bundled) are presented. The physical
      properties of the SWNTs are introduced, followed by the conceptual framework and
      characteristics of their Raman spectra. Each Raman feature, namely the radial
      breathing mode, the tangential G band, combination modes and disorder-induced
      bands are discussed, addressing their physical origin, as well as their
      capability for characterizing SWNT properties.

PMID- 15482982
TI  - Resonant Raman spectroscopy of nanotubes.
AB  - Single and double resonances in Raman scattering are introduced and six criteria
      for the observation and identification of double resonances stated. The
      experimental situation in carbon nanotubes is reviewed in view of these criteria.
      The evidence for the D mode and the high-energy mode is found to be overwhelming
      for a double-resonance process to take place, whereas the nature of the radial
      breathing-mode Raman process remains undecided at this point. Consequences for
      the application of Raman scattering to the characterization of nanotubes are
      discussed.

PMID- 15482983
TI  - Surface-enhanced Raman scattering on single-wall carbon nanotubes.
AB  - Exploiting the effect of surface-enhanced Raman scattering (SERS), the Raman
      signal of single-wall carbon nanotubes (SWNTs) can be enhanced by up to 14 orders
      of magnitude when the tubes are in contact with silver or gold nanostructures and
      Raman scattering takes place predominantly in the enhanced local optical fields
      of the nanostructures. Such a level of enhancement offers exciting opportunities
      for ultrasensitive Raman studies on SWNTs and allows resonant and non-resonant
      Raman experiments to be done on single SWNTs at relatively high signal levels.
      Since the optical fields are highly localized within so-called "hot spots" on
      fractal silver colloidal clusters, lateral confinement of the Raman scattering
      can be as small as 5 nm, allowing spectroscopic selection of a single nanotube
      from a larger population. Moreover, since SWNTs are very stable "artificial
      molecules" with a high aspect ratio and a strong electron-phonon coupling, they
      are unique "test molecules" for investigating the SERS effect itself and for
      probing the "electromagnetic field contribution" and "charge transfer
      contribution" to the effect. SERS is also a powerful tool for monitoring the
      "chemical" interaction between the nanotube and the metal nanostructure.

PMID- 15482984
TI  - Raman spectroscopy of fullerenes and fullerene-nanotube composites.
AB  - The discovery of fullerenes in 1985 opened a completely new field of materials
      research. Together with the single-wall carbon nanotubes (SWCNTs) discovered
      later, these curved carbon networks are a playground for pure as well as applied
      science. We present a review of Raman spectroscopy of fullerenes, SWCNTs and
      composite materials. Beginning with pristine C(60), we discuss intercalated C(60)
      compounds and polymerized C(60), as well as higher and endohedral fullerenes.
      Concerning SWCNTs, we show how the diameter distribution can be obtained from the
      Raman spectra and how doping modifies the spectra. Finally, the Raman response of
      C(60) encapsulated into SWCNTs (C(60) peapods) is discussed.

PMID- 15482985
TI  - Raman spectroscopy of carbon-nanotube-based composites.
AB  - Recent developments in the application of Raman spectroscopy to carbon-nanotube
      based composite materials are reviewed. This technique may be used to identify
      carbon nanotubes, access their dispersion in polymers, evaluate nanotube/matrix
      interactions and detect polymer phase transitions. The Raman spectra of nanotubes
      can also be used to quantify the strain or stress transferred to nanotubes from
      the surrounding environment and to investigate local stresses and strains in
      polymers and composites. A polarized Raman technique was developed to detect the
      stress or strain in a matrix using randomly dispersed single-walled nanotubes.
      This technique has been used to detect and map stress fields in model fibre
      polymer composites. The stress distributions around fibre breaks were mapped and
      compared with classical load transfer models.

PMID- 15482986
TI  - Raman spectroscopy of polyconjugated molecules and materials: confinement effect
      in one and two dimensions.
AB  - The effect of the confinement of pi electrons in one- and two-dimensional domains
      is illustrated with several examples ranging from linear polyene chains to planar
      molecules with honeycomb structure. Theoretical computations and specific Raman
      experiments on molecular materials demonstrate that a molecular approach provides
      a unified key to the interpretation of the Raman response both of linear
      polyconjugated polymers (polyacetylene) and of nanostructured graphitic
      materials.

PMID- 15482987
TI  - UV Raman spectroscopy of hydrocarbons.
AB  - In this paper, the UV Raman spectra of a large number of saturated and alkyl
      substituted monocyclic, bicyclic and polycyclic aromatic hydrocarbons are
      obtained at 220 and 233 nm excitation wavelengths. Also included are nitrogen-
      and sulphur-containing hydrocarbons. The spectra obtained are fluorescence free,
      even for such highly fluorescent compounds as perylene, consistent with earlier
      reports of UV Raman spectra of hydrocarbons. The hydrocarbon UV Raman spectra
      exhibit greatly improved signal-to-noise ratio when in the neat liquid or
      solution state compared with the neat solid state, suggesting that some surface
      degradation occurs under the conditions used here. Assignments are given for most
      of the bands and clear marker bands for the different classes of hydrocarbons are
      readily observable, although their relative intensities vary greatly. These
      results are discussed in the context of structure and symmetry to develop a
      consistent, molecular-based model of vibrational group frequencies.

PMID- 15482988
TI  - Raman spectroscopy of amorphous, nanostructured, diamond-like carbon, and
      nanodiamond.
AB  - Raman spectroscopy is a standard characterization technique for any carbon
      system. Here we review the Raman spectra of amorphous, nanostructured, diamond
      like carbon and nanodiamond. We show how to use resonant Raman spectroscopy to
      determine structure and composition of carbon films with and without nitrogen.
      The measured spectra change with varying excitation energy. By visible and
      ultraviolet excitation measurements, the G peak dispersion can be derived and
      correlated with key parameters, such as density, sp(3) content, elastic constants
      and chemical composition. We then discuss the assignment of the peaks at 1150 and
      1480 cm(-1) often observed in nanodiamond. We review the resonant Raman, isotope
      substitution and annealing experiments, which lead to the assignment of these
      peaks to trans-polyacetylene.

PMID- 15482989
TI  - Low-frequency Raman and Brillouin spectroscopy from graphite, diamond and diamond
      like carbons, fullerenes and nanotubes.
AB  - Inelastic light scattering by acoustic phonons (Brillouin scattering) is a useful
      tool for probing material properties at the submicrometre scale. In media which
      are statistically homogeneous at this scale, it gives access to the acoustic
      properties and the elastic moduli. In nanostructures it probes the vibrational
      properties at the mesoscopic scale. Applications to carbonaceous materials are
      reviewed.

PMID- 15482990
TI  - Raman spectroscopy of diamond and doped diamond.
AB  - The optimization of diamond films as valuable engineering materials for a wide
      variety of applications has required the development of robust methods for their
      characterization. Of the many methods used, Raman microscopy is perhaps the most
      valuable because it provides readily distinguishable signatures of each of the
      different forms of carbon (e.g. diamond, graphite, buckyballs). In addition it is
      non-destructive, requires little or no specimen preparation, is performed in air
      and can produce spatially resolved maps of the different forms of carbon within a
      specimen. This article begins by reviewing the strengths (and some of the
      pitfalls) of the Raman technique for the analysis of diamond and diamond films
      and surveys some of the latest developments (for example, surface-enhanced Raman
      and ultraviolet Raman spectroscopy) which hold the promise of providing a more
      profound understanding of the outstanding properties of these materials. The
      remainder of the article is devoted to the uses of Raman spectroscopy in diamond
      science and technology. Topics covered include using Raman spectroscopy to assess
      stress, crystalline perfection, phase purity, crystallite size, point defects and
      doping in diamond and diamond films.

PMID- 15482991
TI  - Radical treatment of non-small cell lung cancer: a meeting of The British
      Institute of Radiology, held at The Royal Marsden Hospital, Thursday 5th February
      2004.

PMID- 15482992
TI  - Breast cancer: improving outcome following adjuvant radiotherapy.
AB  - In the treatment of early breast cancer adjuvant irradiation improves local
      control following both mastectomy and breast-conserving surgery. For women at
      high risk of relapse it also increases survival. Breast radiotherapy is usually
      given using simple planning techniques and serious morbidity is unusual. The
      greatest concern following adjuvant breast irradiation is of an increase in
      cardiovascular mortality after 15-20 years. New techniques of breast irradiation
      including conformal radiotherapy and intensity-modulated radiotherapy (IMRT) have
      been shown to reduce cardiac and lung irradiation. In addition, improved
      dosimetry within the breast may improve both local control and cosmesis. To
      replace current radiotherapy techniques with those requiring more complex
      planning would demand an increase in resources including both machinery and
      staff. In this review we outline the indications and benefits of breast
      radiotherapy along with the planning process. Technical advances are discussed
      within the context of improving outcome at a time of limited national resources.

PMID- 15482993
TI  - Effect of iodine concentration of contrast media on contrast enhancement in
      multislice CT of the pancreas.
AB  - The purpose of this study was to determine the influence of two different iodine
      concentrations of the non-ionic contrast agent, Iomeprol, on contrast enhancement
      in multislice CT (MSCT) of the pancreas. To achieve this MSCT of the pancreas was
      performed in 50 patients (mean age 57+/-14 years) with suspected or known
      pancreatic tumours. The patients were randomly assigned to group A (n=25
      patients) or group B (n=25 patients). There were no statistically significant
      differences in age, height or weight between the patients of the two groups. The
      contrast agent, Iomeprol, was injected with iodine concentrations of 300 mg ml(
      1) in group A (130 ml, injection rate 5 ml s(-1)) and 400 mg ml(-1) in group B
      (98 ml, injection rate 5 ml s(-1)). Arterial and portal venous phase contrast
      enhancement (HU) of the vessels, organs, and pancreatic masses were measured and
      a qualitative image assessment was performed by two independent readers. In the
      arterial phase, Iomeprol 400 led to a significantly greater enhancement in the
      aorta, superior mesenteric artery, coeliac trunk, pancreas, pancreatic
      carcinomas, kidneys, spleen and wall of the small intestine than Iomeprol 300.
      Portal venous phase enhancement was significantly greater in the pancreas,
      pancreatic carcinomas, wall of the small intestine and portal vein with Iomeprol
      400. The two independent readers considered Iomeprol 400 superior over Iomeprol
      300 concerning technical quality, contribution of the contrast agent to the
      diagnostic value, and evaluability of vessels in the arterial phase. No
      differences were found for tumour delineation and evaluability of infiltration of
      organs adjacent to the pancreas between the two iodine concentrations. In
      conclusion the higher iodine concentration leads to a higher arterial phase
      contrast enhancement of large and small arteries in MSCT of the pancreas and
      therefore improves the evaluability of vessels in the arterial phase.

PMID- 15482994
TI  - Routine transradial access for conventional cerebral angiography: a single
      operator's experience of its feasibility and safety.
AB  - The purpose of this study is to describe a single operator's experience with the
      feasibility and safety of transradial access in conventional cerebral
      angiography. 153 patients were enrolled consecutively. Among them, 20 patients
      were not suitable for transradial access. A Simmons catheter was used.
      Haemostasis was achieved using a compressive dressing of the wrist. We analysed
      the success rates of the arterial puncture and the successful catheterization
      rate for each supra-aortic vessel as well as all complications. The arterial
      access was successful in 96.3%. The supra-aortic vessels were catheterized with
      success rates of 99.2% (127/128) for the left subclavian artery and 100% for the
      other arteries. The mean procedure time was 19.3 min (range 10-55 min).
      Haemostasis was successfully achieved in every case. The most frequent
      complication was arm pain which occurred in 37 patients (28.9%). In conclusion,
      transradial selective cerebral angiography with a reversed-angle catheter is
      technically feasible and safe. It might be helpful in imaging follow-up of
      patients with arterial stenting or coil embolisation of the cerebral aneurysms.
      Modification of the catheter design is required to improve the selectivity of the
      supra-aortic branches.

PMID- 15482995
TI  - Image quality and dose evaluation in spiral chest CT examinations of patients
      with lung carcinoma.
AB  - A study was undertaken to assess the quality of general chest CT examinations for
      indication of lung carcinoma according to the criteria proposed in the European
      Commission (EC) Guidelines, and to investigate their usefulness in the
      optimization of this practice. The criteria were evaluated for a sample of 100
      examinations from five radiology departments in the Madrid area featuring single
      slice helical CT scanners with special emphasis on radiation dose and image
      quality. To determine the degree of compliance with the image criteria
      considered, the examinations were independently evaluated twice by five
      radiologists from the participating centres. A subsequent selection of the
      observers was made according to the consistency and independence of their
      readings. Dose measurements carried out in parallel supplied data to estimate the
      values of the CT dose indices (CTDI), dose-length product (DLP) and effective
      dose (E). The results show good compliance with the image criteria used - between
      93% and 98% on average at the different sites, with variable degrees of internal
      deviation. 10 out of a total of 16 criteria proposed in the EC guidelines were
      met by practically all the examinations in the sample. The average weighted CTDI
      (CTDI(w)) values per site were in the range of 13-19 mGy; those of DLP were
      between 263 mGy cm and 577 mGy cm, and those of effective dose between 4 mSv and
      9 mSv. The highest mean DLP value was below but close to the reference value
      proposed in the EC Document (650 mGy cm). In general, a weak correlation or no
      correlation at all was found between image quality scores and patient dose (DLP).

PMID- 15482996
TI  - Therapeutic external irradiation in women of reproductive age: risk estimation of
      hereditary effects.
AB  - Exposure of women of childbearing age to ionizing radiation may result in
      induction of genetic disorders in future generations. This study aims to estimate
      the risk of hereditary effects attributable to therapeutic external irradiation
      in women. An anthropomorphic phantom was used to simulate radiotherapy in female
      patients and ovarian dose was measured for irradiation of brain, breast and lung
      cancer, and for treatment of Hodgkin's disease. These malignancies are among the
      most common tumours presenting in women of reproductive age. Dose measurements
      were undertaken using thermoluminescent dosemeters and all exposures were made
      with 6 MV X-ray beams. The dose to ovaries was found to be 2-3 cGy, 8-11 cGy and
      11-15 cGy depending on the distance from the primary irradiation field during
      radiotherapy of brain, breast and lung cancer, respectively. The corresponding
      ovarian dose resulting from treatment of supradiaphragmatic and
      infradiaphragmatic Hodgkin's disease was 18-25 cGy and 128-356 cGy, respectively.
      A small excess risk of genetic diseases of (1-15) x 10(-4) was estimated for
      radiotherapy above the diaphragm. Pelvic irradiation resulted in an increased
      risk of hereditary effects of (77-214) x 10(-4).

PMID- 15482997
TI  - Diffusion-weighted MRI in the evaluation of renal lesions: preliminary results.
AB  - The purpose of this study was to evaluate the capability and the reliability of
      diffusion-weighted MRI in the evaluation of normal kidney and different renal
      lesions. 39 patients (10 normal volunteers and 29 patients with known renal
      lesions) underwent MRI of the kidneys by using a 1.5 T superconducting magnet.
      Axial fat suppressed turbo spin echo (TSE) T(2) and coronal fast field echo (FFE)
      T(1) or TSE T(1) weighted images were acquired for each patient. Diffusion
      weighted (DW) images were obtained in the axial plane during breath-hold (17 s)
      with a spin-echo echo planar imaging (SE EPI) single shot sequence (repetition
      time (TR)=2883 ms, echo time (TE)=61 ms, flip angle=90 degrees ), with b value of
      500 s mm(-2). 16 slices were produced with slice thickness of 7 mm and interslice
      gap of 1 mm. An apparent diffusion coefficient (ADC) map was obtained at each
      slice position. The ADC was measured in an approximately 1 cm region of interest
      (ROI) within the normal renal parenchyma, the detected renal lesions and the
      collecting system if dilated. ADC values in normal renal parenchyma ranged from
      1.72 x 10(-3) mm(2) s(-1) to 2.65 x 10(-3) mm(2) s(-1), while ADC values in
      simple cysts (n=13) were higher (2.87 x 10(-3) mm(2) s(-1) to 4.00 x 10(-3) mm(2)
      s(-1)). In hydronephrotic kidneys (n=6) the ADC values of renal pelvis ranged
      from 3.39 x 10(-3) mm(2) s(-1) to 4.00 x 10(-3) mm(2) s(-1). In cases of
      pyonephrosis (n=3) ADC values of the renal pelvis were found to be lower than
      those of renal pelvis of hydronephrotic kidneys (0.77 x 10(-3) mm(2) s(-1) to
      1.07 x 10(-3) mm(2) s(-1)). Solid benign and malignant renal tumours (n=7) showed
      ADC values ranging between 1.28 x 10(-3) mm(2) s(-1) and 1.83 x 10(-3) mm(2) s(
      1). In conclusion diffusion-weighted MR imaging of the kidney seems to be a
      reliable way to differentiate normal renal parenchyma and different renal
      diseases. Clinical experience with this method is still preliminary and further
      studies are required.

PMID- 15482998
TI  - Patient dose optimization in plain radiography based on standard exposure
      factors.
AB  - A computational technique for assessing patient dose in plain radiography is
      described allowing a large number of examinations to be assessed and enabling
      dose optimization to be promoted. Entrance surface dose (ESD) was calculated for
      more than 1500 standard exposure settings in an initial dose assessment.
      Validation of the technique showed good agreement with thermoluminescent
      dosimetry and showed broad agreement between the standard exposures and the
      exposure settings used in practice. The dose assessment was repeated 18 months
      later using the same techniques for almost 2000 standard exposure settings. In
      both cases, calculated doses showed good compliance with national diagnostic
      reference levels where available. Suggested investigation levels were established
      and set at twice the mean dose for each of 47 examinations. Radiology departments
      were encouraged to review and optimize doses exceeding these levels. The computed
      mean ESD in the review study was less than the corresponding value in the initial
      study in 37 of the 47 examinations. The dose reduction was attributable partly to
      equipment replacement, but primarily to optimization of exposure settings. The
      technique employed here provides a valid and cost effective method of complying
      with statutory requirements for the assessment of representative patient dose and
      is useful in assisting the ongoing process of dose optimization.

PMID- 15482999
TI  - A review of factors affecting patient doses for barium enemas and meals.
AB  - A study of patient doses for barium enema and meal examinations has been carried
      out for hospitals in the West of Scotland to assess the impact of dose reduction
      facilities on new X-ray equipment. Dose-area product (DAP) information has been
      collected on examinations for groups of patients at 20 hospitals and results
      reviewed together with data on equipment performance measurements. Median DAPs
      for barium enemas and meals were 15.7 Gy cm(2) and 4.8 Gy cm(2), respectively,
      and effective doses estimated from the results are 3.5+/-0.7 mSv and 1.5+/-0.5
      mSv, respectively. These doses are lower than those reported in earlier studies
      and in previous surveys in the West of Scotland. The reduction in dose is linked
      primarily to the low dose facilities available on newer X-ray equipment, such as
      low dose pulsed fluoroscopy, digital imaging facilities and use of copper
      filtration. Use of the image intensifier for decubitus images on C-arm units
      employed for barium enemas also gives a significantly lower dose. Equipment with
      copper filtration had the lowest doses. The reduction in effective dose will be
      significantly less than the reduction in DAP for units in which a copper filter
      is included and the adoption of lower diagnostic reference levels is proposed for
      units with this facility. It is important that the operators are aware of the low
      dose imaging options on their equipment in order that techniques can be fully
      optimized.

PMID- 15483000
TI  - Extraosseous uptake of metastatic lymph nodes of ureteral cancer on 99Tcm
      hydroxymethylene diphosphonate bone scintigraphy.

PMID- 15483001
TI  - Suitability of resin-coated photographic paper for skin dose measurement during
      fluoroscopically-guided X-ray procedures.
AB  - The need for mapping skin doses during fluoroscopically-guided X-ray procedures
      has been described by a number of institutions and experts. Different large
      photographic or X-ray films placed on the patient's skin have been found to be
      useful for recording doses up to 1.0-2.0 Gy - depending on the film - and up to
      15 Gy using radiochromic films. Though the upper limit of the film sensitivity is
      seldom exceeded during interventional procedures, the main disadvantage of the X
      ray films is still the excessive sensitivity for long, high dose procedures.
      Radiochromic films show poor definition for doses below 0.5 Gy and are expensive.
      The goal of the present paper is to analyse the possibilities of using common
      resin-coated photographic paper for this purpose. Sensitometric curves obtained
      with different paper types processed in conventional X-ray film automatic
      processors demonstrate that some of them can be used with better results than X
      ray films at a very low cost. Doses from about 10 mGy to near 3.0 Gy can be
      measured with good accuracy using a variety of glossy photographic papers.

PMID- 15483002
TI  - Case report: polycythaemia vera presenting as massive splenic infarction and
      liquefaction.

PMID- 15483003
TI  - Case report: lumbar artery bleeding as a complication of percutaneous nephrostomy
      in a patient with coagulopathy.
AB  - A case of severe lumbar artery bleeding as a complication of percutaneous
      nephrostomy (PCN) is presented. A 70-year-old man with coagulation disorder
      (factor VIII deficiency) underwent left PCN because of left hydronephrosis and
      abnormal renal function. The procedure was complicated by a major haemorrhage
      from the left first lumbar artery into the left posterior pararenal space. This
      case illustrates bleeding from the lumbar artery in a patient with coagulation
      disorder resulting in a fatal outcome. CT can provide the diagnosis, while
      angiography with embolisation is an effective means to control the bleeding.
      These examinations should be performed as soon as possible.

PMID- 15483004
TI  - Case report: spontaneous spinal epidural haematoma during pregnancy: case report
      and review of the literature.
AB  - Spontaneous epidural haematoma is rare in pregnancy and only five cases have been
      reported. We present a case of a 31-year-old female G2P1 who at 32 weeks of
      gestation developed progressive ascending paralysis and numbness to a level of
      approximately T4. An urgent MRI of the spine was performed, which demonstrated a
      posterior epidural lesion at T1-T4 level. The lesion showed signal changes
      consistent with an epidural haematoma in the hyperacute stage. An emergency
      cesarean section was performed followed by spinal decompression and removal of an
      epidural haematoma. The patient's neurological function subsequently improved.
      The diagnosis and management of spontaneous epidural haematoma in pregnancy is
      presented with a review of the literature.

PMID- 15483005
TI  - Case report: resolution of symptomatic epidural fibrosis following treatment with
      combined pentoxifylline-tocopherol.
AB  - Epidural fibrosis (EF) is a major cause of failed back surgery syndrome (FBSS),
      which induces disabling radiculopathy for which no effective medical treatment
      exists. Our understanding of the fibrosis mechanisms and our clinical and
      experimental results for the treatment of radiation-induced fibrosis prompted us
      to postulate that EF might respond to treatment with combined pentoxifylline
      (PTX)-tocopherol (Vit.E). 6 weeks after lumbar spine surgery, a 28-year-old man
      presented with recurrent left L5 sciatica without disc herniation on MRI in
      December 1993. From 1993 to 1997, he had unrelieved back and leg pain, which
      became increasingly resistant to intensive medical treatment and to a spinal cord
      stimulator, and confined him to bed as from December 1997. In 1998, a lumbar CT
      scan showed an area of left L4-L5 EF measuring 12 mm x 12 mm, without disc
      herniation. From April 1998, oral PTX (800 mg day(-1)) and Vit.E (1000 IU day(
      1)) were administered daily for 3.5 years and well tolerated. Clinical
      improvement began during the third month of treatment and continued until total
      regression of clinical symptoms April 2001. Lumbar MRI in November 2001 showed a
      surface area of residual EF half the size of the initial area. This is the first
      report to indicate that antifibrotic treatment using combined PTX-Vit.E may be of
      potential benefit in the treatment of post-operative EF. Additional studies are
      required to confirm this potential.

PMID- 15483006
TI  - Case report: internal and external jugular vein thrombosis with marked
      accumulation of FDG.
AB  - We report an unusual case of idiopathic internal and external jugular vein
      thrombosis. Positron emission tomography (PET) using (18)F-fluoro-2-deoxy-D
      glucose (FDG), which was conducted to assess subclinical malignancy, revealed
      intense uptake of FDG, corresponding to thrombus within the left internal and
      external jugular veins. Although FDG-PET is widely used in differentiating
      between malignant and benign diseases, we should bear in mind that this benign
      entity can demonstrate high accumulation of FDG.

PMID- 15483007
TI  - Sacral insufficiency fracture.
AB  - Insufficiency fractures of the sacrum are not uncommon and usually occur in
      osteoporotic bone with minimal or unremembered trauma. However, they appear to be
      relatively under-diagnosed and this pictorial review aims to highlight the
      condition, discuss the expected imaging features and some of the potential
      imaging pitfalls. Owing to its relationship with osteoporosis, the majority occur
      in elderly females and are frequently bilateral, often presenting as low back
      pain. Plain radiographs are generally normal and both clinician and radiologist
      need to consider the possibility of sacral insufficiency fracture to allow prompt
      accurate diagnosis and correct treatment. Lumbar spine MRI is among the first
      investigations performed and can enable the correct diagnosis to be made.
      Occasionally the MR appearances can mimic tumour or osteomyelitis. The "H" sign
      on an isotope bone scan is considered diagnostic in the right clinical setting,
      but this sign is often not present. CT is useful to confirm the diagnosis and
      exclude tumour or infection.

PMID- 15483008
TI  - A pathognomonic MRI finding in a patient with ataxia and hearing loss.

PMID- 15483009
TI  - Demyelination in the brain as a paraneoplastic disorder.

PMID- 15483011
TI  - Phase II studies of modern drugs directed against new targets: if you are fazed,
      too, then resist RECIST.

PMID- 15483010
TI  - Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients.
AB  - PURPOSE: To evaluate the safety, toxicity, in vivo immunologic activation, and
      maximum-tolerated dose (MTD) of EMD 273063 (hu14.18-IL-2) in patients with
      metastatic melanoma. PATIENTS AND METHODS: Thirty-three patients were treated
      with EMD 273063, a humanized anti-GD2 monoclonal antibody (mAb) linked to
      interleukin-2 (IL-2). EMD 273063 was given as a 4-hour intravenous infusion on
      days 1, 2, and 3 of week 1. Patients with stabilization or regression of disease
      could receive a second course of treatment at week 5. Dose levels evaluated were
      0.8, 1.6, 3.2, 4.8, 6.0, and 7.5 mg/m2/d. RESULTS: Nineteen of 33 patients
      completed course 1 with stable disease and went on to receive course 2. Eight
      patients had stable disease on completion of course 2. Grade 3 adverse events
      included hypophosphatemia (11 patients), hyperglycemia (three patients),
      hypotension (two patients), thrombocytopenia (one patient), hypoxia (three
      patients), elevated hepatic transaminases (two patients), and hyperbilirubinemia
      (one patient). Opioids were required for treatment-associated arthralgias and/or
      myalgias during 17 of 52 treatment courses. No grade 4 adverse events were
      observed. Dose-limiting toxicities at the MTD included hypoxia, hypotension, and
      elevations in AST/ALT. Grade 3 toxicities were anticipated based on prior studies
      of IL-2 or anti-GD2 mAbs, and all resolved. Immune activation was induced, as
      measured by lymphocytosis, increased peripheral-blood natural killer activity,
      and cell numbers, and increased serum levels of the soluble alpha chain of the IL
      2 receptor complex. CONCLUSION: Treatment with the immunocytokine EMD 273063
      induced immune activation and was associated with reversible clinical toxicities
      at the MTD of 7.5 mg/m2/d in melanoma patients.

PMID- 15483012
TI  - MSH6 mutations in hereditary nonpolyposis colon cancer: another slice of the pie.

PMID- 15483013
TI  - T-cell chauvinists versus antibody advocates--can't we all just get along?

PMID- 15483014
TI  - Clinical outcome of lymphoma patients after idiotype vaccination is correlated
      with humoral immune response and immunoglobulin G Fc receptor genotype.
AB  - PURPOSE: The unique immunoglobulin idiotype (Id) expressed by each B-cell
      lymphoma is a target for immunotherapy. Vaccination with Id induces humoral
      and/or cellular anti-Id immune responses. However, the clinical impact of these
      anti-Id immune responses is unknown. We and others have previously reported that
      immunoglobulin G Fc receptor (FcgammaR) polymorphisms predict the clinical
      response of lymphoma patients to passive anti-CD20 antibody infusions. In this
      study, we tested whether anti-Id immune responses or FcgammaR polymorphisms
      associate with clinical outcome of patients who received Id vaccination. PATIENTS
      AND METHODS: We analyzed 136 patients with follicular lymphoma who had received
      Id vaccination. The anti-Id immune responses were measured and FcgammaRIIIa and
      FcgammaRIIa polymorphisms were determined and correlated with clinical outcome
      for these patients. RESULTS: Patients who mounted humoral immune responses had a
      longer progression-free survival (PFS) than those who did not (8.21 v 3.38 years;
      P = .018). Patients with FcgammaRIIIa 158 valine/valine (V/V) genotype also had a
      longer PFS than those with valine/phenylalanine (V/F) or
      phenylalanine/phenylalanine (F/F) genotypes (V/V, 8.21 v V/F, 3.38 years; P =
      .004; v F/F, 4.47 years; P = .035). Multivariate analysis using the Cox
      proportional hazards model showed that V/V genotype and humoral immune responses
      were independent positive predictors for PFS. CONCLUSION: This study is the first
      to identify the predictive value of FcgammaR polymorphism on clinical outcome in
      patients who received active immunotherapy with tumor antigen vaccines. Our
      results imply that the antibodies induced against a tumor antigen are beneficial
      and that FcgammaR-bearing cells mediate an antitumor effect by killing antibody
      coated tumor cells.

PMID- 15483015
TI  - Prolonged clinical and molecular remission in patients with low-grade or
      follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy:
      9-year follow-up.
AB  - PURPOSE: Long-term follow-up with updated time to disease progression (TTP) and
      duration of response (DR) data are presented from a multicenter, phase II trial
      of rituximab/cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)
      combination therapy in 40 patients with CD20+, B-cell, non-Hodgkin's lymphoma
      (NHL). Revised response rates based on International Workshop Response Criteria
      are also provided. PATIENTS AND METHODS: Enrollment began in April 1994 and
      consisted of patients with histologically confirmed, low-grade, B-cell lymphoma
      who had received no prior chemotherapy or who had no more than four prior
      standard therapies. Patients received six cycles of CHOP and six infusions of
      rituximab. RESULTS: Eight (21%) of the 38 treated patients were classified as
      International Working Formulation (IWF) A, 16 (42%) were IWF B, 13 (34%) were IWF
      C, and one (3%) was IWF D. Nine (24%) of 38 patients had received prior
      chemotherapy. Nine (24%) of 38 were considered poor risk according to the
      Follicular Lymphoma International Prognostic Index. Overall response rate was
      100%; 87% of patients achieved a complete response or unconfirmed complete
      response. The median TTP and DR were 82.3 months and 83.5 months, respectively.
      Seven of eight patients who were bcl-2 positive at baseline converted to
      negative, and three of the seven patients have sustained the molecular remission.
      CONCLUSION: Although a cure has not been found yet for follicular NHL, the R-CHOP
      combination provides a lengthy response duration in patients with relapsed or
      newly diagnosed indolent NHL.

PMID- 15483016
TI  - Lower incidence of colorectal cancer and later age of disease onset in 27
      families with pathogenic MSH6 germline mutations compared with families with MLH1
      or MSH2 mutations: the German Hereditary Nonpolyposis Colorectal Cancer
      Consortium.
AB  - PURPOSE: The aim of the study was the analysis of the involvement and phenotypic
      manifestations of MSH6 germline mutations in families suspected of hereditary
      nonpolyposis colorectal cancer (HNPCC). PATIENTS AND METHODS: Patients were
      preselected among 706 families by microsatellite instability,
      immunohistochemistry, and/or exclusion of MLH1 or MSH2 mutations and were
      subjected to MSH6 mutation analysis. Clinical and molecular data of MSH6 mutation
      families were compared with data from families with MLH1 and MSH2 mutations.
      RESULTS: We identified 27 families with 24 different pathogenic MSH6 germline
      mutations, representing 3.8% of the total of the families, and 14.7% of all
      families with DNA mismatch repair (MMR) gene mutations (n = 183). The median age
      of onset of colorectal cancer in putative mutation carriers was 10 years higher
      for MSH6 (54 years; 95% CI, 51 to 56) compared with MLH1 and MSH2 (44 years; 95%
      CI, 43 to 45; log-rank test, P = .0038). Relative to other malignant tumors,
      colorectal cancer was less frequent in MSH6 families compared with MLH1 and MSH2
      families (Fisher's exact test, P < .001). In contrast, the frequency of non-HNPCC
      associated tumors was increased (Fisher's exact test, P < .001). CONCLUSION:
      Later age of disease onset and lower incidence of colorectal cancer may
      contribute to a lower proportion of identified MSH6 mutations in families
      suspected of HNPCC. However, in approximately half of these families, at least
      one patient developed colorectal or endometrial cancer in the fourth decade of
      life. Therefore, a surveillance program as stringent as that for families with
      MLH1 or MSH2 mutations is recommended.

PMID- 15483017
TI  - Multicenter phase II study of the oral MEK inhibitor, CI-1040, in patients with
      advanced non-small-cell lung, breast, colon, and pancreatic cancer.
AB  - PURPOSE: This multicenter, open-label, phase II study was undertaken to assess
      the antitumor activity and safety of the oral mitogen-activated extracellular
      signal regulated kinase kinase (MEK) inhibitor, CI-1040, in breast cancer, colon
      cancer, non-small-cell lung cancer (NSCLC), and pancreatic cancer. PATIENTS AND
      METHODS: Patients with advanced colorectal, NSCLC, breast, or pancreatic cancer
      received oral CI-1040 continuously at 800 mg bid. All patients had measurable
      disease at baseline, a performance status of 2 or less, and adequate bone marrow,
      liver, and renal function. Expression of pERK, pAkt, and Ki-67 was assessed in
      archived tumor specimens by quantitative immunohistochemistry. RESULTS: Sixty
      seven patients with breast (n = 14), colon (n = 20), NSCLC (n = 18), and
      pancreatic (n = 15) cancer received a total of 194 courses of treatment (median,
      2.0 courses; range, one to 14 courses). No complete or partial responses were
      observed. Stable disease (SD) lasting a median of 4.4 months (range, 4 to 18
      months) was confirmed in eight patients (one breast, two colon, two pancreas, and
      three NSCLC patients). Treatment was well tolerated, with 81% of patients
      experiencing toxicities of grade 2 or less severity. Most common toxicities
      included diarrhea, nausea, asthenia, and rash. A mild association (P < .055)
      between baseline pERK expression in archived tumor specimens and SD was observed.
      CONCLUSION: CI-1040 was generally well tolerated but demonstrated insufficient
      antitumor activity to warrant further development in the four tumors tested. PD
      0325901, a second generation MEK inhibitor, has recently entered clinical
      development and, with significantly improved pharmacologic and pharmaceutical
      properties compared with CI-1040, it may better test the therapeutic potential of
      MEK inhibition in cancer.

PMID- 15483018
TI  - Long-term follow-up for locally advanced and inflammatory breast cancer patients
      treated with multimodality therapy.
AB  - PURPOSE: To determine long-term event-free (EFS) and overall survival (OS) for
      patients with stage III breast cancer treated with combined-modality therapy.
      PATIENTS AND METHODS: Between 1980 and 1988, 107 patients with stage III breast
      cancer were prospectively enrolled for study at the National Cancer Institute and
      stratified by whether or not they had features of inflammatory breast cancer
      (IBC). Patients were treated to best response with cyclophosphamide, doxorubicin,
      methotrexate, fluorouracil, leucovorin, and hormonal synchronization with
      conjugated estrogens and tamoxifen. Patients with pathologic complete response
      received definitive radiotherapy to the breast and axilla, whereas patients with
      residual disease underwent mastectomy, lymph node dissection, and radiotherapy.
      All patients underwent six additional cycles of adjuvant chemotherapy. RESULTS:
      OS and EFS were obtained with a median live patient follow-up time of 16.8 years.
      The 46 IBC patients had a median OS of 3.8 years and EFS of 2.3 years, compared
      with 12.2 and 9.0 years, respectively, in stage IIIA breast cancer patients.
      Fifteen-year OS survival was 20% for IBC versus 50% for stage IIIA patients and
      23% for stage IIIB non-IBC. Pathologic response was not associated with improved
      survival for stage IIIA or IBC patients. Presence of dermal lymphatic invasion
      did not change the probability of survival in clinical IBC patients. CONCLUSION:
      Fifteen-year follow-up of stage IIIA and inflammatory breast cancer is rarely
      reported; IBC patients have a poor long-term outlook.

PMID- 15483020
TI  - Immediate versus deferred hormonal treatment for patients with prostate cancer
      who are not suitable for curative local treatment: results of the randomized
      trial SAKK 08/88.
AB  - PURPOSE: To determine if immediate hormonal therapy is advantageous compared with
      deferred treatment in newly diagnosed asymptomatic prostate cancer patients who,
      for any reason, were not candidates for curative local treatment. PATIENTS AND
      METHODS: Between February 1988 and February 1992, 197 patients with a median age
      of 76 years (range, 56 to 86 years) were randomly assigned to receive either
      immediate or deferred orchiectomy on symptomatic progression. The two groups did
      not differ significantly in clinical or laboratory parameters; 67% had T3-4
      tumors and 20% had lymph node metastases. Patient accrual was stopped prematurely
      because of a similar competing trial. Therefore, observation time was prolonged
      to achieve the desired number of events and statistical power. RESULTS: Deferred
      orchiectomy was necessary in 58% of the patients. Median time to disease
      progression was 2.8 years less than for patients with immediate orchiectomy.
      However, overall pain-free time from random assignment to symptomatic progression
      after immediate or deferred orchiectomy, and performance status, were identical
      in both groups. Cancer-specific survival tended to be longer in the immediate
      group (P = .09) but there was no difference in overall survival between the two
      groups (P = .96). The median hemoglobin value decreased significantly after
      immediate orchiectomy (P < .001). CONCLUSION: For elderly, asymptomatic patients
      not undergoing curative local treatment, we were unable to show any major
      advantage of immediate compared with deferred hormonal treatment regarding
      quality of life or overall survival in our limited number of patients. Disabling
      complications were prevented in the deferred-treatment arm by careful follow-up;
      42% of these patients never required any tumor-specific treatment.

PMID- 15483019
TI  - Is eligibility for a chemotherapy protocol a good prognostic factor for invasive
      bladder cancer after radical cystectomy?
AB  - PURPOSE: To assess whether eligibility to an adjuvant chemotherapy protocol in
      itself represents a good prognostic factor after radical cystectomy for bladder
      cancer. PATIENTS AND METHODS: Between April 1984 and May 1989, our institution
      entered 35 patients with invasive bladder cancer into the Swiss Group for
      Clinical and Epidemiological Cancer Research (SAKK) study 09/84. They were
      randomly assigned to either observation or three postoperative courses of
      cisplatin monotherapy after cystectomy. This study had a negative result. The
      outcome of these 35 patients (protocol group) was compared with an age- and tumor
      stage-matched cohort (matched group; n = 35) who also underwent cystectomy during
      the same period, but were not entered into the SAKK study, as well as the
      remaining 57 patients treated during the study period for the same indication
      (remaining group). RESULTS: Median overall survival decreased from 76.3 months in
      the protocol group to 52.1 months in the matched group and to 20.3 months in the
      remaining group. The respective times of median recurrence-free survival were
      67.2, 16.0, and 9.4 months. Tumor progression occurred in 46% of the protocol
      group compared with 69% in the matched group and 65% in the remaining group (P <
      .05). Cancer-related death was noted in 40% of the protocol group, 57% in the
      matched group, and 56% in the remaining group. CONCLUSION: These data suggest
      that being willing and fit enough for a chemotherapy protocol is a good
      prognostic factor for invasive bladder cancer. This eligibility bias emphasizes
      the need for prospective, randomized trials, and indicates that single-group
      studies using historical or matched controls have to be interpreted with caution.

PMID- 15483021
TI  - Response to paclitaxel, topotecan, and topotecan-cyclophosphamide in children
      with untreated disseminated neuroblastoma treated in an upfront phase II
      investigational window: a pediatric oncology group study.
AB  - PURPOSE: Most children older than 1 year of age with metastatic neuroblastoma
      (NB) die despite intensive chemotherapy and bone marrow transplantation. The
      Pediatric Oncology Group conducted a study of paclitaxel, topotecan, and
      topotecan-cyclophosphamide (topo-cyclo) in newly diagnosed children with stage IV
      NB. PATIENTS AND METHODS: There were 102 patients enrolled between September 1993
      and October 1995; two of them were later shown to be ineligible. Of the remaining
      100 patients, the first cohort of 33 patients received paclitaxel 350 mg/m(2)
      intravenously (IV) over 24 hours every 14 to 21 days; the next 33 patients
      received topotecan 2 mg/m(2)/d for 5 days IV every 21 days; a third cohort of 34
      patients were treated with IV cyclophosphamide 250 mg/m(2) followed by topotecan
      0.75 mg/m(2) each day for 5 days every 21 days. Patients were re-evaluated after
      two courses and then treated with intensive induction therapy and bone marrow
      transplantation. RESULTS: Objective responses (complete response + partial
      response + mixed response) were documented in 67% of children who received
      topotecan, 76% after topo-cyclo, and 25% after paclitaxel. Four patients had
      grade 3 to 4 allergic reactions to paclitaxel; most patients developed grade 3 to
      4 marrow suppression after topotecan or topo-cyclo. Neither disease-free survival
      nor overall survival differed significantly between children who received a phase
      II agent and those who did not. The 6-year disease-free survival and overall
      survival rates for all 100 children were 18% +/- 5% and 26% +/- 5%, respectively.
      CONCLUSION: Topotecan and topo-cyclo are active in children with NB, are well
      tolerated, and should be evaluated further in combination regimens.

PMID- 15483022
TI  - GABAergic system gene expression predicts clinical outcome in patients with
      neuroblastoma.
AB  - PURPOSE: Neuroblastoma (NB) is a common childhood malignancy characterized by
      heterogeneous clinical behavior. The purpose of this study was to identify
      potential NB biomarkers that may improve outcome prediction. PATIENTS AND
      METHODS: The suppression subtractive hybridization (SSH) technique was used to
      identify the genes differentially expressed between NB and control tissue. RNA
      isolated from 235 primary NB tumor samples obtained from the Children's Cancer
      Group was evaluated for expression of the candidate markers using quantitative
      reverse transcriptase polymerase chain reaction (Taqman assays). The association
      between the mRNA expression levels in the identified candidate genes and clinical
      outcome was evaluated. RESULTS: SSH analysis identified differential expression
      of members of the GABAergic gene family in NB. Lower levels of gamma-aminobutyric
      acid (GABA) receptor-associated protein (GABARAP) gene expression predict
      decreased survival among all patients. GABA(A) delta receptor subunit gene
      expression was predictive of a poor outcome among Evans stage IV-S patients. An
      index of five coexpressed GABA(A) receptor subunits was identified (GABA(A)
      profile [GAP score]). Patients with a higher GAP score (> -1) had a survival
      advantage. Multivariate analysis showed that GABARAP and GABA(A) alpha2 receptor
      subunit gene expression levels and GAP score remained predictors of clinical
      outcome after accounting for current prognostic indicators. CONCLUSION:
      Dysregulation of the GABAergic system may constitute a fundamental event in the
      development of NB, and assessment of GABAergic system gene expression could
      provide improved patient stratification and potential new therapies.

PMID- 15483023
TI  - Midline carcinoma of children and young adults with NUT rearrangement.
AB  - PURPOSE: A balanced chromosomal translocation, t(15;19), resulting in the BRD4
      NUT oncogene, has been identified in a lethal carcinoma of young people, a
      disease described primarily in case reports. We sought to amass a more definitive
      series of tumors with NUT and/or BRD4 gene rearrangements and to determine
      distinct clinicopathologic features. PATIENTS AND METHODS: Carcinomas (N = 98) in
      young individuals (median age, 32.5 years) were screened for NUT and BRD4
      rearrangements using dual-color fluorescence in situ hybridization. Four
      published carcinomas with BRD4 and NUT rearrangements were also evaluated.
      Immunophenotypic analyses were performed. RESULTS: Eleven tumors had NUT gene
      rearrangements, including eight with BRD4-NUT fusions and three with novel
      rearrangements, which were designated as NUT variant. All NUT-rearranged
      carcinomas (NRCs) arose from midline epithelial structures, including the first
      example arising below the diaphragm. Patients were young (median age, 17.6
      years). Squamous differentiation (seen in 82% of NRCs) was particularly striking
      in NUT-variant cases. In this first description of NUT-variant carcinomas, the
      average survival (96 weeks, n = 3) was longer than for BRD4-NUT carcinomas (28
      weeks, n = 8). Strong CD34 expression was found in six of 11 NRCs but in zero of
      45 NUT wild-type carcinomas. CONCLUSION: NRCs arise from midline structures in
      young people, and NRCs with BRD4-NUT are highly lethal, despite intensive
      therapies. NUT-variant carcinomas might have a less fulminant clinical course
      than those with BRD4-NUT fusions. CD34 expression is characteristic in NRCs and,
      therefore, holds promise as a diagnostic test for this distinctive
      clinicopathologic entity.

PMID- 15483024
TI  - Frequency and heritability of WT1 mutations in nonsyndromic Wilms' tumor
      patients: a UK Children's Cancer Study Group Study.
AB  - PURPOSE: Constitutional WT1 mutations in patients with Wilms' tumor (WT) have
      specifically been associated with genitourinary abnormalities, such as
      cryptorchidism and hypospadias. We sought to ascertain the frequency and
      heritability of constitutional WT1 mutations in nonsyndromic WT patients.
      PATIENTS AND METHODS: Constitutional DNA from 282 patients treated at seven
      United Kingdom Children's Cancer Study Group centers was screened for WT1
      mutations using heteroduplex analysis. Bidirectional sequencing was used to
      confirm the mutation and to analyze the corresponding parental DNA samples.
      RESULTS: Five different constitutional WT1 mutations were identified in six
      children. Mutations in four patients were confirmed to be de novo, and all five
      mutations are predicted to produce truncated protein. The WT1 mutation group had
      a young median age at diagnosis of 13.8 months, compared with 34.9 months in the
      group in whom no WT1 mutations were found; four were female and two were male;
      and all tumors were of favorable histology. The three tumors with known
      histologic subtype were stromal-predominant. Contrary to expectation, four of six
      mutations occurred in children with unilateral tumors without any associated
      genitourinary abnormality. CONCLUSION: Constitutional WT1 mutations occur with a
      low frequency (2.1%; 95% CI, 0.8% to 4.6%) in nonsyndromic WT patients. Most
      mutations occurred in children with unilateral WT without associated
      genitourinary abnormalities, creating difficulties in identifying individuals
      with germline mutations on phenotype alone. Two factors that may indicate that an
      individual is carrying a germline WT1 mutation are an early age of onset and
      stromal-predominant histology of the WT.

PMID- 15483025
TI  - Clinical decisions associated with positron emission tomography in a prospective
      cohort of patients with suspected or known cancer at one United States center.
AB  - PURPOSE: In 2001, Medicare approved reimbursement of F-18 fluorodeoxyglucose
      positron emission tomography (PET) for a variety of cancers. PET has been
      observed to be more accurate than other imaging in cancer patients, but the
      impact of PET on management in routine practice is uncertain. PATIENTS AND
      METHODS: We studied a prospective cohort having noninvestigational PET at one
      university center. Before and after PET, a questionnaire was administered to
      solicit information regarding each physician's preceding actions, intended
      management, and probability estimates. RESULTS: Seventy-one physicians provided
      data on 248 patients, of whom 40% had new or suspected cancer and 60% were
      undergoing restaging or had suspected recurrence. Lung, lymphoma, and head/neck
      cancers accounted for two thirds of cases. Sixteen physicians made 64% of
      requests. Physicians changed their intended management in 61% of patients (95%
      CI, 54% to 66%). For individual physicians ordering at least 10 scans, the
      average kappa was 0.16 (range, -0.04 to 0.36), reflecting only slight level of
      agreement between their before and after PET plan. PET was associated with a
      change in 90 (79%) of 114 patients if the pre-PET intended plan involved more
      testing or biopsy. In 32% of cases, physicians changed to a treatment from a
      nontreatment strategy. The therapeutic goal and mode changed in 22 (7%) and 21
      cases (8%), respectively. CONCLUSION: This study confirms that physicians often
      change their decision making based on PET. This impact is likely due to combined
      effects of PET's improved accuracy and reduced physician uncertainty. Physicians
      may also be overconfident in interpreting PET and use it as the final arbiter
      after an extensive evaluation in lieu of tissue biopsy.

PMID- 15483026
TI  - Circulating deoxyribonucleic Acid as prognostic marker in non-small-cell lung
      cancer patients undergoing chemotherapy.
AB  - PURPOSE: Circulating cell-free DNA is present in increased amounts in the blood
      of cancer patients, but the clinical relevance of this phenomenon remains
      unclear. We conducted a clinical study to assess the value of circulating DNA as
      a prognostic marker in patients with non-small-cell lung cancer (NSCLC). PATIENTS
      AND METHODS: A standard protocol for the quantification of circulating DNA by
      real-time polymerase chain reaction was set up and validated at two oncology
      units. One hundred eighty-five informed patients with NSCLC and 46 healthy
      controls were included in the study. DNA concentrations were determined in paired
      plasma and serum samples and analyzed for a relationship with leukocyte counts
      and lactate dehydrogenase (LDH) levels. DNA concentrations in healthy controls
      and in patients were compared, and cutoff levels for plasma and serum DNA were
      determined. Patient survival was analyzed relative to baseline DNA
      concentrations, and the relationship between tumor responses and changes in DNA
      concentrations was assessed in patients receiving chemotherapy. RESULTS: We found
      a significant correlation between increased plasma DNA concentrations and
      elevated LDH levels (P = .009), advanced tumor stage (P < .003), and poor
      survival (P < .001). Tumor progression after chemotherapy was significantly (P =
      .006) associated with increasing plasma DNA concentrations. Serum DNA
      concentrations strongly correlated (P < .001) with leukocyte counts. CONCLUSION:
      Our data demonstrate that quantification of plasma DNA is an accurate technique
      amenable to standardization, which might complement current methods for the
      prediction of patient survival. This approach might be considered for evaluation
      in large prospective studies.

PMID- 15483027
TI  - Regulation of p27 by S-phase kinase-associated protein 2 is associated with
      aggressiveness in non-small-cell lung cancer.
AB  - PURPOSE: The F-box protein S-phase kinase-associated protein 2 (Skp2) is one of
      the positive regulators of the cell cycle that promote ubiquitin-mediated
      proteolysis of the cyclin-dependent kinase inhibitor p27. In this study, we
      investigated the significance of Skp2 expression in human non-small-cell lung
      cancer (NSCLC). PATIENTS AND METHODS: Clinicopathologic features and
      immunohistochemical expression of Skp2 and p27 proteins were studied in 138
      patients with NSCLC. Survival analyses were performed using the Kaplan-Meier
      method and the Cox regression model. To analyze the role of Skp2 in vitro, NSCLC
      cells were transfected with an Skp2-expressing vector or small interfering RNA.
      RESULTS: Skp2 was overexpressed in males, smokers, patients with squamous cell
      carcinomas, and patients with poorly differentiated cancers (P = .034, < .0001, <
      .0001, and .002, respectively). The multivariant analysis revealed that Skp2
      expression is an independent prognostic factor for survival in NSCLC. An inverse
      relationship of Skp2 with p27 expression was observed (P = .012), and patients
      with both a higher expression of Skp2 and a lower expression of p27 showed a
      significantly unfavorable prognosis (P = .0002). In vitro ectopic expression of
      Skp2 in NSCLC cells reduced the protein level of p27. Conversely, induction of
      Skp2 siRNA increased the protein level of p27, leading to growth inhibition in
      NSCLC cells. CONCLUSION: Skp2 overexpression is closely associated with the
      suppression of p27 and the aggressiveness in NSCLC. It also could be a
      therapeutic target in NSCLC.

PMID- 15483028
TI  - Web-based survey of fertility issues in young women with breast cancer.
AB  - PURPOSE: Young women with breast cancer often seek advice about whether treatment
      will affect their fertility. We sought to gain a better understanding of women's
      attitudes about fertility and how these concerns affect decision making. PATIENTS
      AND METHODS: We developed a survey about fertility issues for young women with a
      history of early-stage breast cancer. The survey was e-mailed to all registered
      Young Survival Coalition survivor members (N = 1,702). E-mail reminders were
      used. RESULTS: Six hundred fifty-seven eligible respondents completed the survey.
      Mean age at breast cancer diagnosis was 32.9 years; mean current age was 35.8
      years. Ninety percent of women were white; 62% were married; 76% were college
      graduates. Stages at diagnosis were as follows: 0, 10%; I, 27%; II, 47%; III,
      13%. Sixty-two percent of women were within 2 years of diagnosis. Fifty-seven
      percent recalled substantial concern at diagnosis about becoming infertile with
      treatment. In multivariate logistic regression, greater concern about infertility
      was associated with wish for children/more children (odds ratio [OR], 120; P <
      .0001), number of prior pregnancies (OR, 0.78; P = .01), and prior difficulty
      conceiving (OR, 1.86; P = .08). Twenty-nine percent of women reported that
      infertility concerns influenced treatment decisions. Seventy-two percent of women
      reported discussing fertility concerns with their doctors; 51% felt their
      concerns were addressed adequately. Women seemed to overestimate their risk of
      becoming postmenopausal with treatment. CONCLUSION: Fertility after treatment is
      a major concern for young women with breast cancer. There is a need to
      communicate with and educate young patients regarding fertility issues at
      diagnosis and a need for future research directed at preserving fertility for
      young breast cancer survivors.

PMID- 15483029
TI  - Health-related quality of life and psychosocial status in breast cancer
      prognosis: analysis of multiple variables.
AB  - PURPOSE: Evidence that psychosocial status and health-related quality of life
      (HRQOL) are associated with breast cancer (BC) outcomes is weak and inconsistent.
      We examined prognostic effects of these factors in a prospective cohort study.
      PATIENTS AND METHODS: Three hundred ninety-seven women with surgically resected
      T1 to T3, N0/N1, M0 BC completed the European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire (Core 30 items), Profile of
      Mood States, Psychosocial Adjustment to Illness Scale, Impact of Events Scale,
      Mental Adjustment to Cancer Scale, and the Courtauld Emotional Control Scale 2
      months after diagnosis and 1 year later. Data on tumor-related factors,
      treatment, and outcomes were obtained prospectively from medical records, and Cox
      survival analyses were performed. RESULTS: Mean age was 52.0 +/- 9.9 years. Two
      hundred twenty-five women had T1, 136 women had T2, 16 women had T3, and 20 women
      had TX tumors; 127 were N1. One hundred thirteen women received adjuvant
      chemotherapy, 130 received hormone therapy, 45 received both, and 109 received
      neither. We investigated 140 prognostic associations; four were found to be
      statistically significant at a P value of </= .05 (three fewer than expected by
      chance). Two were in the hypothesized direction of effect, and two were in the
      opposite direction. All arose from measurements 1 year after diagnosis, which
      were most susceptible to confounding by treatment. There was no evidence of
      consistency of associations across outcomes or questionnaires. These results are
      in keeping with chance as the explanation for our statistically significant
      findings. CONCLUSION: HRQOL and psychosocial status at diagnosis and 1 year later
      are not associated with medical outcome in women with early-stage BC.

PMID- 15483030
TI  - Racial/Ethnic differences in functional outcomes in the 5 years after diagnosis
      of localized prostate cancer.
AB  - PURPOSE: We investigated racial/ethnic differences in functional outcomes up to 5
      years after diagnosis among men with aggressively treated localized prostate
      cancer. PATIENTS AND METHODS: Patients were from the Prostate Cancer Outcomes
      Study, a population-based cohort study that surveyed patients at 6, 12, 24, and
      60 months after diagnosis. Analyses were stratified by primary treatment.
      Racial/ethnic differences at each time point were assessed using Generalized
      Estimating Equations, adjusting for pretreatment function, age at diagnosis,
      secondary treatment, and other confounders. An adjusted summary score for each
      functional domain was calculated for each time period. RESULTS: Patients included
      1,475 non-Hispanic white, 321 African-American, and 279 Hispanic prostate cancer
      patients. After 60 months, among prostatectomy patients, African-Americans had
      significantly higher sexual function scores than non-Hispanic whites (43.9 v
      36.1; P = .02), but were more likely to have a moderate to big problem with
      sexual function (50.6% v 44.4%; P = .04). African-Americans also had higher
      urinary function scores at 5 years than non-Hispanic whites (78.5 v 72.4; P =
      .04) and were less likely to have problems with incontinence. Changes in sexual
      and bowel function after radiotherapy showed no significant racial/ethnic
      differences. CONCLUSION: This long-term cohort study found that, among
      prostatectomy patients, African-Americans had better recovery of sexual and
      urinary function at 60 months after diagnosis that was likely to be of mild
      clinical significance, despite reporting more problems with sexual function than
      non-Hispanic whites. More study is necessary to understand reasons for these
      differences. In contrast, no racial/ethnic differences in recovery from
      radiotherapy were found.

PMID- 15483031
TI  - Quality of life after transhiatal compared with extended transthoracic resection
      for adenocarcinoma of the esophagus.
AB  - PURPOSE: To assess 3 years of quality of life in patients with esophageal cancer
      in a randomized trial comparing limited transhiatal resection with extended
      transthoracic resection. PATIENTS AND METHODS: Quality-of-life questionnaires
      were sent at baseline and at 5 weeks; 3, 6, 9, and 12 months; and 1.5, 2, 2.5,
      and 3 years after surgery. Physical and psychological symptoms, activity level,
      and global quality of life were assessed with the disease-specific Rotterdam
      Symptom Checklist. Generic quality of life was measured with the Medical Outcomes
      Study Short Form-20. RESULTS: A total of 199 patients participated. Physical
      symptoms and activity level declined after the operation and gradually returned
      toward baseline within the first year (P < .01). Psychological well-being
      consistently improved after baseline (P < .01), whereas global quality of life
      showed a small initial decline followed by continuous gradual improvement (P <
      .01). Quality of life stabilized in the second and third year. Three months after
      the operation, patients in the transhiatal esophagectomy group (n = 96) reported
      fewer physical symptoms (P = .01) and better activity levels (P < .01) than
      patients in the transthoracic group (n = 103), but no differences were found at
      any other measurement point. For psychological symptoms and global quality of
      life, no differences were found at any follow-up measurement. A similar pattern
      was found for generic quality of life. CONCLUSION: No lasting differences in
      quality of life of patients who underwent either transhiatal or transthoracic
      resection were found. Compared with baseline, quality of life declined after the
      operation but was restored within a year in both groups.

PMID- 15483032
TI  - Suicide risk in cancer patients from 1960 to 1999.
AB  - PURPOSE: Suicide risk is reportedly higher for cancer patients than for the
      general population, but estimates vary and analyses of trends are few. The aim of
      the present study was to determine whether cancer patients had a higher suicide
      risk between 1960 and 1999. PATIENTS AND METHODS: A cohort comprising patients
      from the Cancer Registry of Norway 1960 to 1997 was linked to suicide diagnosis
      in the Register of Deaths at Statistics Norway and observed during 1960 to 1999.
      The cohort consisted of all cancer patients registered in the Cancer Registry of
      Norway 1960 to 1997 (N = 490,245 patients with 520,823 cancer diagnoses). Suicide
      was defined according to death certificates based on the International
      Classification of Diseases (versions 7, 8, 9, and 10). RESULTS: During the
      period, 589 cancer patients (407 males and 182 females) committed suicide. The
      relative risk was elevated for males and females, with standardized mortality
      ratios (SMRs) of 1.55 (95% CI, 1.41 to 1.71) and 1.35 (95% CI, 1.17 to 1.56),
      respectively. Risk was highest in the first months after diagnosis. For both
      sexes, there was a significant decrease in the relative suicide risk over
      decades. The risk was markedly increased among male patients with cancer of
      respiratory organs (SMR, 4.08; 95% CI, 2.96 to 5.47). Otherwise, the SMRs varied
      from 0.76 to 3.67 across cancer types. CONCLUSION: Cancer may be a risk factor
      for suicide, particularly shortly after diagnosis. However, the relative risk
      gradually decreased during the period 1960 to 1999.

PMID- 15483033
TI  - Putting the rap on Akt.
AB  - The protein kinase Akt is activated in a wide variety of cancers, and this
      activation results in enhanced resistance to apoptosis through multiple
      mechanisms. This article reviews the control of Akt activation by the opposing
      actions of the oncogene phosphoinositide 3-kinase (PI3-K) and the tumor
      suppressor phosphatase and tensin homolog deleted on chromosome 10. The
      activation of Akt by transforming mutations, such as the amplification of HER
      2/neu in breast cancer and the formation of the BCR/ABL fusion gene in chronic
      myelogenous leukemia, seems to be essential for the transforming activity of
      these oncogenes. We discuss several of the proposed mechanisms for the
      antiapoptotic effect of activated Akt, including the inhibition of the
      proapoptotic protein Bad, downregulation of death receptors, and enhancement of
      the glycolytic rate. Increased glycolysis is seen in many malignancies and forms
      the basis for the increasing use of positron emission tomography imaging for
      diagnosis and staging. Finally, we discuss rapamycin and its analogs, which are
      now in trials as antineoplastic therapy; these agents show particular promise in
      tumors in which Akt has been activated.

PMID- 15483034
TI  - Unusual sites of Hodgkin's lymphoma: CASE 1. HIV-associated Hodgkin's lymphoma of
      the stomach.

PMID- 15483035
TI  - Unusual sites of Hodgkin's lymphoma: CASE 2. Hodgkin's lymphoma of the CNS
      masquerading as meningioma.

PMID- 15483036
TI  - Unusual sites of Hodgkin's lymphoma: CASE 3. Cholemic nephrosis in Hodgkin's
      lymphoma with liver involvement.

PMID- 15483038
TI  - HER-2 overexpression in breast tumors lacking gene amplification.

PMID- 15483039
TI  - Long-term bisphosphonate treatment of bone metastases from renal cell carcinoma.

PMID- 15483040
TI  - Need for further information on pemetrexed study.

PMID- 15483042
TI  - Subthreshold low-frequency repetitive transcranial magnetic stimulation over the
      premotor cortex modulates writer's cramp.
AB  - Writer's cramp, or focal hand dystonia, is characterized by involuntary
      coactivation of antagonist or unnecessary muscles while writing or performing
      other tasks. Although the mechanism underlying this muscle overactivation is
      unknown, recent studies of changes in cerebral blood flow during writing have
      demonstrated a reduction in the activation of the primary motor cortex (MC) and
      hyperactivity of parts of the frontal non-primary motor areas. Therefore, any
      measures that decrease the activities of non-primary motor areas such as the
      premotor cortex (PMC) and the supplementary motor area (SMA) might improve
      dystonic symptoms. To explore this possibility, we studied nine patients with
      writer's cramp and seven age-matched control subjects, using subthreshold low
      frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS), which
      exerts an inhibitory action on the cortex. Previous studies have demonstrated
      shortened cortical silent periods in dystonia, suggesting deficient cortical
      inhibition in the MC. We compared the silent periods and computer-assisted
      ratings of handwriting before and after rTMS applied to the MC, SMA or PMC. We
      also used the sham coil for control runs. Stimulation of the PMC but not the MC
      significantly improved the rating of handwriting (mean tracking error from the
      target, P = 0.004; pen pressure, P = 0.01) and prolonged the silent period (P =
      0.02) in the patient group. rTMS over the other sites or using a sham coil in the
      patient group or trials in the control group revealed no physiological or
      clinical changes. This increased susceptibility of the PMC in dystonia suggests
      that the lack of inhibition in the MC is secondary to the hyperactivity of PMC
      neurons. Inhibition of the PMC using rTMS could provide a therapeutic measure of
      writer's cramp.

PMID- 15483043
TI  - Neuropathology of white matter disease in Leber's hereditary optic neuropathy.
AB  - Leber's hereditary optic neuropathy (LHON) is associated with point mutations in
      the mitochondrial DNA (mtDNA), coding for a mitochondrial respiratory chain
      complex I subunit. It is characterized by bilateral, usually sequential, optic
      neuropathy and may co-occur with multiple sclerosis-like white matter lesions.
      Despite repeated clinical reports including MRI and histopathological examination
      of the visual system, neuropathological descriptions of LHON associated with
      multiple sclerosis-like syndrome are lacking. We present here the case of a
      female patient with a point mutation at nucleotide position T14484C, who suffered
      from relapsing episodes of visual loss of both eyes and consecutively developed
      Hashimoto thyroiditis as well as widespread demyelinating CNS lesions outside the
      visual system. She died of bronchopneumonia at the age of 44 years, after a
      disease duration of 19 years, with progressive deterioration, epileptic seizures
      and immobility. Immunohistochemical analysis on formalin-fixed and paraffin
      embedded tissue reveals a spectrum of neuropathological changes, including
      actively and inactively demyelinating plaques in the white matter and optic
      nerve, vacuolation and cystic necrosis with CD8-positive T cells in the frontal
      lobe, axonal damage, and vacuolation of white matter. Tissue destruction is
      associated with upregulation of mitochondrial manganese superoxide dismutase
      within the lesions and an increase in the expression of inducible nitric oxide
      synthase within macrophages and microglia. This variable phenotype of extraoptic
      LHON disease suggests that mtDNA mutations may affect the nervous system on a
      common metabolic basis and occasionally may aggravate or initiate autoimmune
      pathology.

PMID- 15483044
TI  - Dysfunction of the brain calcium channel CaV2.1 in absence epilepsy and episodic
      ataxia.
AB  - The molecular basis of idiopathic generalized epilepsy remains poorly understood.
      Absence epilepsy with 3 Hz spike-wave EEG is one of the most common human
      epilepsies, and is associated with significant morbidity. Several spontaneously
      occurring genetic mouse models of absence epilepsy are caused by dysfunction of
      the P/Q-type voltage-gated calcium channel CaV2.1. Such mice exhibit a primary
      generalized spike-wave EEG, with frequencies in the range of 5-7 Hz, often
      associated with ataxia, evidence of cerebellar degeneration and abnormal
      posturing. Previously, we identified a single case of severe primary generalized
      epilepsy with ataxia associated with CaV2.1 dysfunction, suggesting a possible
      link between this channel and human absence epilepsy. We now report a family in
      which absence epilepsy segregates in an autosomal dominant fashion through three
      generations. Five members exhibit a combination of absence epilepsy (with 3 Hz
      spike-wave) and cerebellar ataxia. In patients with the absence epilepsy/ataxia
      phenotype, genetic marker analysis was consistent with linkage to the CACNA1A
      gene on chromosome 19, which encodes the main pore-forming alpha1A subunit of
      CaV2.1 channels (CaV2.1alpha1). DNA sequence analysis identified a novel point
      mutation resulting in a radical amino acid substitution (E147K) in CaV2.1alpha1,
      which segregated with the epilepsy/ataxia phenotype. Functional expression
      studies using human CACNA1A cDNA demonstrated that the E147K mutation results in
      impairment of calcium channel function. Impaired function of the brain calcium
      channel CaV2.1 may have a central role in the pathogenesis of certain cases of
      primary generalized epilepsy, particularly when associated with ataxia, which may
      be wrongly ascribed to anticonvulsant medication.

PMID- 15483045
TI  - The effect of pre-mutation of X chromosome CGG trinucleotide repeats on brain
      anatomy.
AB  - Expanded trinucleotide repeats are associated with several neuropsychiatric
      disorders, including fragile X syndrome (FraX) which is the most common inherited
      form of mental retardation. It is currently thought that FraX results from having
      >200 CGG trinucleotide repeats, with consequent methylation of the fragile X
      mental retardation gene (FMR1) and loss of FMR1 protein (FMRP). Pre-mutation
      carriers of FraX (with 55-200 CGG trinucleotide repeats) were originally
      considered unaffected, although recent studies challenge this view. However,
      there are few studies on the effect of pre-mutation trinucleotide repeat
      expansion on the male human brain using quantitative MRI. Also the results of
      prior investigations may be confounded because people were selected on the basis
      of clinical and neurological features, and not genetic phenotype. We compared the
      brain anatomy of 20 adult male pre-mutation members of known FraX families with
      20 healthy male controls. The two groups did not differ significantly in age,
      intelligence quotient (IQ) or handedness. We also investigated whether any
      observed effects were associated with: (i) ageing; (ii) expansion of pre-mutation
      CGG trinucleotide repeats; (iii) reduction in the percentage of lymphocytes
      staining with anti-FMRP antibodies [%FMRP(+) lymphocytes]; and (iv) elevation of
      FMR1 mRNA levels. Male pre-mutation carriers of FraX, compared with matched
      controls, had significantly less voxel density in several brain regions,
      including the cerebellum, amygdalo-hippocampal complex and thalamus. Within pre
      mutation carriers of FraX, ageing, increases in the number of CGG trinucleotide
      repeats and decreases in %FMRP(+) lymphocytes were associated with decreasing
      voxel density of regions previously identified as decreased relative to controls.
      Regional grey and white matter density is significantly affected in male pre
      mutation carriers of FraX recruited on the basis of genetic, not clinical,
      phenotype. The association of voxel density reduction and ageing is consistent
      with observations of a subgroup of older pre-mutation males who present with
      cognitive decline. Moreover, our findings suggest, for the first time, an
      association between voxel density reduction and genetic variation in FraX.

PMID- 15483046
TI  - Suppressing versus releasing a habit: frequency-dependent effects of prefrontal
      transcranial magnetic stimulation.
AB  - When subjects are required to generate a random sequence of numbers they
      typically produce too many forward and backward 'counts' (e.g. 5-6, 4-3). This
      counting bias is interpreted as the consequence of an interference by overlearned
      tendencies to arrange numbers according to their natural order. Inhibition of
      such well-learned routines is known to rely on frontal lobe functioning. We
      examined differential effects of slow (1 Hz) and fast (10 Hz) repetitive
      transcranial magnetic stimulation (rTMS) over the left or right dorsolateral
      prefrontal cortex (DLPFC) on random number generation (RNG) performance. Eighteen
      healthy men performed an RNG task. Those subjects stimulated over the left DLPFC
      showed a frequency-dependent rTMS effect: counting bias was significantly reduced
      after the 1 Hz stimulation compared with baseline, but significantly exaggerated
      after the 10 Hz stimulation compared with 1 Hz stimulation. In contrast, the
      sequences of the subjects stimulated over the right DLPFC showed the well-known
      excess of counting in all conditions (i.e. baseline, 1 Hz and 10 Hz). These
      findings confirm the functional importance of specifically the left DLPFC in
      sequential response production and show, for the first time, that rTMS affects
      cognitive processing in a frequency-dependent manner.

PMID- 15483047
TI  - Microglia in the cerebral wall of the human telencephalon at second trimester.
AB  - We have recently begun to gain a clearer understanding of the phasing and
      patterns of colonization of the developing human brain by microglia. In this
      study we investigated the distribution, morphology and phenotype of microglia
      specifically within the wall of the human telencephalon from 12 to 24 gestational
      weeks (gw), a period that corresponds to the development of thalamocortical
      fibres passing through the transient subplate region of the developing cerebral
      wall. Sections from a total of 45 human fetal brains were immunoreacted to detect
      CD68 and MHC class II antigens and histochemically reacted with RCA-1 and tomato
      lectins. These markers were differentially expressed by anatomically discrete
      populations of microglia in the cerebral wall: two cell populations were noted
      during the initial phase of colonization (12-14 gw): (i) CD68++ RCA-1+ MHC II-
      amoeboid cells aligned within the subplate, and (ii) RCA-1++ CD68- MHC II-
      progenitors in the marginal layer and lower cortical plate that progressively
      ramified within the subplate, without seemingly passing through an 'amoeboid'
      state. At this stage microglia were largely absent from the germinal layers and
      the intermediate zone. From 14 to 15 gw, however, MHC class II positive cells
      were also detected within germinal layers and in the corpus callosum, and these
      cells, which coexpressed CD68 antigen (a marker associated with phagocytosis),
      further populated the lower half of the telencephalon from 18 to 24 gw. These
      findings are discussed in relation to developmental events that take place during
      the second trimester within the wall of the telencephalon.

PMID- 15483048
TI  - Involvement of the ventral premotor cortex in controlling image motion of the
      hand during performance of a target-capturing task.
AB  - The ventral premotor cortex (PMv) has been implicated in the visual guidance of
      movement. To examine whether neuronal activity in the PMv is involved in
      controlling the direction of motion of a visual image of the hand or the actual
      movement of the hand, we trained a monkey to capture a target that was presented
      on a video display using the same side of its hand as was displayed on the video
      display. We found that PMv neurons predominantly exhibited premovement activity
      that reflected the image motion to be controlled, rather than the physical motion
      of the hand. We also found that the activity of half of such direction-selective
      PMv neurons depended on which side (left versus right) of the video image of the
      hand was used to capture the target. Furthermore, this selectivity for a portion
      of the hand was not affected by changing the starting position of the hand
      movement. These findings suggest that PMv neurons play a crucial role in
      determining which part of the body moves in which direction, at least under
      conditions in which a visual image of a limb is used to guide limb movements.

PMID- 15483049
TI  - Homeostatic synaptic plasticity can explain post-traumatic epileptogenesis in
      chronically isolated neocortex.
AB  - Chronically isolated neocortex develops chronic hyperexcitability and focal
      epileptogenesis in a period of days to weeks. The mechanisms operating in this
      model of post-traumatic epileptogenesis are not well understood. We hypothesized
      that the spontaneous burst discharges recorded in chronically isolated neocortex
      result from homeostatic plasticity (a mechanism generally assumed to stabilize
      neuronal activity) induced by low neuronal activity after deafferentation. To
      test this hypothesis we constructed computer models of neocortex incorporating a
      biologically based homeostatic plasticity rule that operates to maintain firing
      rates. After deafferentation, homeostatic upregulation of excitatory synapses on
      pyramidal cells, either with or without concurrent downregulation of inhibitory
      synapses or upregulation of intrinsic excitability, initiated slowly repeating
      burst discharges that closely resembled the epileptiform burst discharges
      recorded in chronically isolated neocortex. These burst discharges lasted a few
      hundred ms, propagated at 1-3 cm/s and consisted of large (10-15 mV)
      intracellular depolarizations topped by a small number of action potentials. Our
      results support a role for homeostatic synaptic plasticity as a novel mechanism
      of post-traumatic epileptogenesis.

PMID- 15483050
TI  - Employers' responses to a play-or-pay mandate: an analysis of California's Health
      Insurance Act of 2003.
AB  - California recently enacted a play-or-pay employer mandate (known as SB 2) to
      expand health insurance coverage to a portion of the state's working uninsured
      population. Implementing SB 2 will change the behavior of employers affected by
      the legislation, with consequences for California's labor market and uninsured
      citizens. This paper applies findings from the literature and an economic
      analysis to California data to estimate the potential reduction in wages,
      quantify the dispersion of risk across employers, and discuss other employment
      effects. These employer responses will reduce the number of uninsured people in
      California who gain eligibility for health coverage under SB 2.

PMID- 15483051
TI  - Coregulation of fibronectin signaling and matrix contraction by tenascin-C and
      syndecan-4.
AB  - Syndecan-4 is a ubiquitously expressed heparan sulfate proteoglycan that
      modulates cell interactions with the extracellular matrix. It is transiently up
      regulated during tissue repair by cells that mediate wound healing. Here, we
      report that syndecan-4 is essential for optimal fibroblast response to the three
      dimensional fibrin-fibronectin provisional matrix that is deposited upon tissue
      injury. Interference with syndecan-4 function inhibits matrix contraction by
      preventing cell spreading, actin stress fiber formation, and activation of focal
      adhesion kinase and RhoA mediated-intracellular signaling pathways. Tenascin-C is
      an extracellular matrix protein that regulates cell response to fibronectin
      within the provisional matrix. Syndecan-4 is also required for tenascin-C action.
      Inhibition of syndecan-4 function suppresses tenascin-C activity and
      overexpression of syndecan-4 circumvents the effects of tenascin-C. In this way,
      tenascin-C and syndecan-4 work together to control fibroblast morphology and
      signaling and regulate events such as matrix contraction that are essential for
      efficient tissue repair.

PMID- 15483052
TI  - BAF53/Arp4 homolog Alp5 in fission yeast is required for histone H4 acetylation,
      kinetochore-spindle attachment, and gene silencing at centromere.
AB  - Nuclear actin-related proteins play vital roles in transcriptional regulation;
      however, their biological roles remain elusive. Here, we characterize Alp5,
      fission yeast homolog of Arp4/BAF53. The temperature-sensitive mutant alp5-1134
      contains a single amino acid substitution in the conserved C-terminal domain
      (S402N) and displays mitotic phenotypes, including chromosome condensation and
      missegregation. Alp5 forms a complex with Mst1-HAT (histone acetyltransferase).
      Consistently, inhibition of histone deacetylases (HDACs), by either addition of a
      specific inhibitor or a mutation in HDAC-encoding clr6+ gene, rescues alp5-1134.
      Immunoblotting with specific antibodies against acetylated histones shows that
      Alp5 is required for histone H4 acetylation at lysines 5, 8, and 12, but not
      histone H3 lysines 9 or 14, and furthermore Clr6 plays an opposing role. Mitotic
      arrest is ascribable to activation of the Mad2/Bub1 spindle checkpoint, in which
      both proteins localize to the mitotic kinetochores in alp5-1134. Intriguingly,
      alp5-1134 displays transcriptional desilencing at the core centromere without
      altering the overall chromatin structure, which also is suppressed by a
      simultaneous mutation in clr6+. This result shows that Alp5 is essential for
      histone H4 acetylation, and its crucial role lies in the establishment of bipolar
      attachment of the kinetochore to the spindle and transcriptional silencing at the
      centromere.

PMID- 15483053
TI  - Intracellular mechanics of migrating fibroblasts.
AB  - Cell migration is a highly coordinated process that occurs through the
      translation of biochemical signals into specific biomechanical events. The
      biochemical and structural properties of the proteins involved in cell motility,
      as well as their subcellular localization, have been studied extensively.
      However, how these proteins work in concert to generate the mechanical properties
      required to produce global motility is not well understood. Using intracellular
      microrheology and a fibroblast scratch-wound assay, we show that cytoskeleton
      reorganization produced by motility results in mechanical stiffening of both the
      leading lamella and the perinuclear region of motile cells. This effect is
      significantly more pronounced in the leading edge, suggesting that the mechanical
      properties of migrating fibroblasts are spatially coordinated. Disruption of the
      microtubule network by nocodazole treatment results in the arrest of cell
      migration and a loss of subcellular mechanical polarization; however, the overall
      mechanical properties of the cell remain mostly unchanged. Furthermore, we find
      that activation of Rac and Cdc42 in quiescent fibroblasts elicits mechanical
      behavior similar to that of migrating cells. We conclude that a polarized
      mechanics of the cytoskeleton is essential for directed cell migration and is
      coordinated through microtubules.

PMID- 15483054
TI  - Role of Unc104/KIF1-related motor proteins in mitochondrial transport in
      Neurospora crassa.
AB  - Eukaryotic cells use diverse cytoskeleton-dependent machineries to control
      inheritance and intracellular positioning of mitochondria. In particular,
      microtubules play a major role in mitochondrial motility in the filamentous
      fungus Neurospora crassa and in mammalian cells. We examined the role of two
      novel Unc104/KIF1-related members of the kinesin family, Nkin2 and Nkin3, in
      mitochondrial motility in Neurospora. The Nkin2 protein is required for
      mitochondrial interactions with microtubules in vitro. Mutant hyphae lacking
      Nkin2 show mitochondrial motility defects in vivo early after germination of
      conidiospores. Nkin3, a member of a unique fungal-specific subgroup of small
      Unc104/KIF1-related proteins, is not associated with mitochondria in wild-type
      cells. However, it is highly expressed and recruited to mitochondria in Deltankin
      2 mutants. Mitochondria lacking Nkin2 require Nkin3 for binding to microtubules
      in vitro, and mitochondrial motility defects in Deltankin-2 mutants disappear
      with up-regulation of Nkin3 in vivo. We propose that mitochondrial transport is
      mediated by Nkin2 in Neurospora, and organelle motility defects in Deltankin-2
      mutants are rescued by Nkin3. Apparently, a highly versatile complement of
      organelle motors allows the cell to efficiently respond to exogenous challenges,
      a process that might also account for the great variety of different
      mitochondrial transport systems that have evolved in eukaryotic cells.

PMID- 15483055
TI  - Dictyostelium PAKc is required for proper chemotaxis.
AB  - We have identified a new Dictyostelium p21-activated protein kinase, PAKc, that
      we demonstrate to be required for proper chemotaxis. PAKc contains a Rac-GTPase
      binding (CRIB) and autoinhibitory domain, a PAK-related kinase domain, an N
      terminal phosphatidylinositol binding domain, and a C-terminal extension related
      to the Gbetagamma binding domain of Saccharomyces cerevisiae Ste20, the latter
      two domains being required for PAKc transient localization to the plasma
      membrane. In response to chemoattractant stimulation, PAKc kinase activity is
      rapidly and transiently activated, with activity levels peaking at approximately
      10 s. pakc null cells exhibit a loss of polarity and produce multiple lateral
      pseudopodia when placed in a chemoattractant gradient. PAKc preferentially binds
      the Dictyostelium Rac protein RacB, and point mutations in the conserved CRIB
      that abrogate this binding result in misregulated kinase activation and
      chemotaxis defects. We also demonstrate that a null mutation lacking the PAK
      family member myosin I heavy chain kinase (MIHCK) shows mild chemotaxis defects,
      including the formation of lateral pseudopodia. A null strain lacking both PAKc
      and the PAK family member MIHCK exhibits severe loss of cell movement, suggesting
      that PAKc and MIHCK may cooperate to regulate a common chemotaxis pathway.

PMID- 15483056
TI  - Regulation of microtubule-dependent recycling at the trans-Golgi network by Rab6A
      and Rab6A'.
AB  - The small GTPase rab6A but not the isoform rab6A' has previously been identified
      as a regulator of the COPI-independent recycling route that carries Golgi
      resident proteins and certain toxins from the Golgi to the endoplasmic reticulum
      (ER). The isoform rab6A' has been implicated in Golgi-to-endosomal recycling.
      Because rab6A but not A', binds rabkinesin6, this motor protein is proposed to
      mediate COPI-independent recycling. We show here that both rab6A and rab6A' GTP
      restricted mutants promote, with similar efficiency, a microtubule-dependent
      recycling of Golgi resident glycosylation enzymes upon overexpression. Moreover,
      we used small interfering RNA mediated down-regulation of rab6A and A' expression
      and found that reduced levels of rab6 perturbs organization of the Golgi
      apparatus and delays Golgi-to-ER recycling. Rab6-directed Golgi-to-ER recycling
      seems to require functional dynactin, as overexpression of p50/dynamitin, or a C
      terminal fragment of Bicaudal-D, both known to interact with dynactin inhibit
      recycling. We further present evidence that rab6-mediated recycling seems to be
      initiated from the trans-Golgi network. Together, this suggests that a recycling
      pathway operates at the level of the trans-Golgi linking directly to the ER. This
      pathway would be the preferred route for both toxins and resident Golgi proteins.

PMID- 15483057
TI  - Cold adaptation in budding yeast.
AB  - We have determined the transcriptional response of the budding yeast
      Saccharomyces cerevisiae to cold. Yeast cells were exposed to 10 degrees C for
      different lengths of time, and DNA microarrays were used to characterize the
      changes in transcript abundance. Two distinct groups of transcriptionally
      modulated genes were identified and defined as the early cold response and the
      late cold response. A detailed comparison of the cold response with various
      environmental stress responses revealed a substantial overlap between
      environmental stress response genes and late cold response genes. In addition,
      the accumulation of the carbohydrate reserves trehalose and glycogen is induced
      during late cold response. These observations suggest that the environmental
      stress response (ESR) occurs during the late cold response. The transcriptional
      activators Msn2p and Msn4p are involved in the induction of genes common to many
      stress responses, and we show that they mediate the stress response pattern
      observed during the late cold response. In contrast, classical markers of the ESR
      were absent during the early cold response, and the transcriptional response of
      the early cold response genes was Msn2p/Msn4p independent. This implies that the
      cold-specific early response is mediated by a different and as yet
      uncharacterized regulatory mechanism.

PMID- 15483058
TI  - Voltage-gated channels and calcium homeostasis in mammalian rod photoreceptors.
AB  - Recent reports on rod photoreceptor neuroprotection by Ca2+ channel blockers have
      pointed out the need to assess the effect of these blockers on mammalian rods.
      However, in mammals, rod electrophysiological characterization has been hampered
      by the small size of these photoreceptors, which were instead extensively studied
      in nonmammalian vertebrates. To further characterize ionic conductances and to
      assess the pharmacology of Ca2+ channels in mammalian rods, freshly dissociated
      pig rod photoreceptors were recorded with the whole cell patch-clamp technique.
      Rod cells expressed 1) a hyperpolarization-activated inward-rectifying
      conductance (I(h)) sensitive to external Cs+; 2) a sustained outward K+ current
      (I(K)) sensitive to tetraethylammonium; 3) a sustained voltage-gated Ca2+ current
      (I(Ca)) sensitive to benzothiazepine (diltiazem) and phenylalkylamine (verapamil)
      derivatives; 4) a Ca(2+)-activated Cl- current (I(Cl(Ca))); and 5) a plasma
      membrane Ca(2+)-ATPase. The Ca2+ current showed a range of activation from
      positive potentials to -60 mV with a maximum between -30 and -20 mV. In contrast
      to other L-type Ca2+ channels, rod Ca2+ channels were blocked at similar and
      relatively high concentrations by the diltiazem isomers and verapamil. The
      biphasic dose-response for D-diltiazem confirmed the low sensitivity of Ca2+
      channels for the molecule. The ATPase, which was localized at the axon terminal,
      was found to contribute to Ca2+ extrusion. These results suggest that the
      electrophysiological features of rod photoreceptors had been preserved during
      evolution from nonmammalian vertebrates to mammals. This work indicates further
      that mammalian rods express nonclassic L-type Ca2+ channels, showing a low
      sensitivity to the diltiazem isomers used in neuroprotective studies.

PMID- 15483059
TI  - Motor-unit activity differs with load type during a fatiguing contraction.
AB  - Despite a similar rate of change in average electromyographic (EMG) activity,
      previous studies have observed different rates of change in mean arterial
      pressure, heart rate, perceived exertion, and fluctuations in motor output during
      the performance of fatiguing contractions that involved different types of loads.
      To obtain a more direct measure of the motor output from the spinal cord, the
      purpose of this study was to compare the discharge characteristics of the same
      motor unit in biceps brachii during the performance of two types of fatiguing
      contractions. In separate tests with the upper arm vertical and the elbow flexed
      to 1.57 rad, the seated subjects maintained either a constant upward force at the
      wrist (force task) or a constant elbow angle (position task) for a prescribed
      duration. The force and position tasks were performed in random order at a target
      force equal to 3.5 +/- 2.1% (mean +/- SD) of the maximal voluntary contraction
      (MVC) force above the recruitment threshold of the isolated motor unit. Each
      subject maintained the two tasks for an identical duration (161 +/- 96 s) at a
      mean target force of 22.2 +/- 13.4% MVC (range: 3-49% MVC). The dependent
      variables included the discharge characteristics of the same motor unit in biceps
      brachii, fluctuations in motor output (force or acceleration), mean arterial
      pressure, heart rate, and rating of perceived exertion. Despite similar increases
      in the amplitude of the averaged EMG (% MVC) for the elbow flexor muscles during
      both tasks (P = 0.60), the rates of increase in mean arterial pressure (P <
      0.001), rating of perceived exertion (P = 0.023), and fluctuations in motor
      output (P = 0.003) were greater during the position task compared with the force
      task. Consistent with these differences, mean discharge rate declined at a
      greater rate during the position task (P = 0.03), and the coefficient of
      variation for discharge rate increased only during the position task (P = 0.02).
      Furthermore, more motor units were recruited during the position task compared
      with the force task (P = 0.01). These findings indicate that despite a comparable
      net muscle torque, the rate of increase in the motor output from the spinal cord
      was greater during the position task.

PMID- 15483060
TI  - Modulation of parabrachial taste neurons by electrical and chemical stimulation
      of the lateral hypothalamus and amygdala.
AB  - The lateral hypothalamus (LH) and the central nucleus of the amygdala (CeA) exert
      an influence on ingestive behavior and are reciprocally connected to gustatory
      and viscerosensory areas, including the nucleus of the solitary tract (NST) and
      the parabrachial nuclei (PbN). We investigated the effects of LH and CeA
      stimulation on the activity of 101 taste-responsive neurons in the hamster PbN.
      Eighty three of these neurons were antidromically activated by stimulation of
      these sites; 57 were antidromically driven by both. Of these 83 neurons, 21 were
      also orthodromically activated--8 by the CeA and 3 by the LH. Additional neurons
      were excited (n = 5) or inhibited (n = 8) by these forebrain nuclei but not
      antidromically activated. Taste stimuli were: 0.032 M sucrose, 0.032 M sodium
      chloride (NaCl), 0.032 M quinine hydrochloride (QHCl), and 0.0032 M citric acid.
      Among the 34 orthodromically activated neurons, more sucrose-best neurons were
      excited than inhibited, whereas the opposite occurred for citric-acid- and QHCl
      best cells. Neurons inhibited by the forebrain responded significantly more
      strongly to citric acid and QHCl than cells excited by these sites. The effects
      of electrical stimulation were mimicked by microinjection of DL-homocysteic acid,
      indicating that cells at these forebrain sites were responsible for these
      effects. These data demonstrate that many individual PbN gustatory neurons
      project to both the LH and CeA and that these areas modulate the gustatory
      activity of a subset of PbN neurons. This neural substrate is likely involved in
      the modulation of taste activity by physiological and experiential factors.

PMID- 15483061
TI  - Spatiotemporal tuning of optic flow inputs to the vestibulocerebellum in pigeons:
      differences between mossy and climbing fiber pathways.
AB  - The pretectum, accessory optic system (AOS), and vestibulocerebellum (VbC) have
      been implicated in the analysis of optic flow and generation of the optokinetic
      response. Recently, using drifting sine-wave gratings as stimuli, it has been
      shown that pretectal and AOS neurons exhibit spatiotemporal tuning. In this
      respect, there are two groups: fast neurons, which prefer low spatial frequency
      (SF) and high temporal frequency (TF) gratings, and slow neurons, which prefer
      high SF-low TF gratings. In pigeons, there are two pathways from the pretectum
      and AOS to the VbC: a climbing fiber (CF) pathway to Purkinje cells (P cells) via
      the inferior olive and a direct mossy fiber (MF) pathway to the granular layer
      (GL). In the present study, we assessed spatiotemporal tuning in the VbC of
      ketamine-anesthetized pigeons using standard extracellular techniques. Recordings
      were made from 17 optic-flow-sensitive units in the GL, presumably granule cells
      or MF rosettes, and the complex spike activity (CSA) of 39 P-cells, which
      reflects CF input. Based on spatiotemporal tuning to gratings moving in the
      preferred direction, eight GL units were classified as fast units, with a primary
      response to low SF-high TF gratings (mean = 0.13 cpd/8.24 Hz), whereas nine were
      slow units preferring high SF-low TF gratings (mean = 0.68 cpd/0.30 Hz). CSA was
      almost exclusively tuned to slow gratings (mean = 0.67 cpd/0.35 Hz). We conclude
      that MF input to the VbC is from both fast and slow cells in the AOS and
      pretectum, whereas the CF input is primarily tuned to slow gratings.

PMID- 15483062
TI  - Dendritic sodium spikelets and low-threshold calcium spikes in turtle olfactory
      bulb granule cells.
AB  - Active dendritic membrane properties were investigated by whole cell recordings
      from adult turtle olfactory bulb granule cells. The laminar structure of the
      olfactory bulb allowed differential polarization of the distal apical dendrites
      versus the somatic part of the cells by an external electric field. Dendritic
      depolarization evoked small (approximately 10 mV) all-or-none depolarizing events
      of approximately 10-ms duration. These spikelets often occurred in bursts at high
      frequency (< or = 250 Hz); they were present despite the application of synaptic
      and gap junction antagonists, but were abolished by TTX and intracellularly
      applied QX314. The spikelets were interpreted as attenuated sodium spikes
      initiated in different branches of the granule cells dendrites. They occurred
      spontaneously, but could also be evoked by excitatory postsynaptic potentials
      (EPSPs) to the distal dendrites. Spikelets initiated by distal excitation could
      function as prepotentials for full sodium spikes, in part depending on the level
      of proximal depolarization. Somatic depolarization by the electric field evoked
      full sodium spikes as well as low-threshold calcium spikes (LTSs). Calcium
      imaging revealed that the electrophysiologically identified LTS evoked from the
      soma was associated with calcium transients in the proximal and the distal
      dendrites. Our data suggest that the LTS in the soma/proximal dendrites plays a
      major role in boosting excitability, thus contributing to the initiation of
      sodium spiking in this compartment. The results furthermore suggest that the LTS
      and the sodium spikes may act independently or cooperatively to regulate
      dendritic calcium influx.

PMID- 15483063
TI  - GABA(B) receptor activation modulates GABA(A) receptor-mediated inhibition in
      chicken nucleus magnocellularis neurons.
AB  - Neurons of nucleus magnocellularis (NM), a division of avian cochlear nucleus
      that performs precise temporal encoding, receive glutamatergic excitatory input
      solely from the eighth nerve and GABAergic inhibitory input primarily from the
      ipsilateral superior olivary nucleus. GABA activates both ligand-gated Cl-
      channels [GABA(A) receptors (GABA(A)Rs)] and G protein-coupled receptors (GABA(B)
      receptors). The net effect of GABA(A)R-mediated input to NM is inhibitory,
      although depolarizing. Several studies have shown that this shunting, inhibitory
      GABAergic input can evoke action potentials in postsynaptic NM neurons, which
      could interfere with their temporal encoding. While this GABA-mediated firing is
      limited by a low-voltage-activated K+ conductance, we have found evidence for a
      second mechanism. We investigated modulation of GABA(A)R-mediated responses by
      GABA(B)Rs using whole cell recording techniques. Bath-applied baclofen, a
      GABA(B)R agonist, produced dose-dependent suppression of evoked inhibitory
      postsynaptic currents (eIPSCs). This suppression was blocked by CGP52432, a
      potent and selective GABA(B)R antagonist. Baclofen reduced the frequency but not
      the amplitude of miniature IPSCs (mIPSCs) and did not affect postsynaptic
      currents elicited by puff application of a specific GABA(A)R agonist muscimol,
      suggesting a presynaptic mechanism for the GABA(B)R-mediated modulation. Firing
      of NM neurons by synaptic stimulation of GABAergic inputs to NM was eliminated by
      baclofen. However, endogenous GABA(B)R activity in the presynaptic inhibitory
      terminals was not observed. We propose that presynaptic GABA(B)Rs function as
      autoreceptors, regulating synaptic strength of GABA(A)R-mediated inhibition, and
      prevent NM neurons from generating firing during activation of the inhibitory
      inputs.

PMID- 15483064
TI  - Comparison of the spatial limits on direction selectivity in visual areas MT and
      V1.
AB  - We recorded responses to apparent motion from directionally selective neurons in
      primary visual cortex (V1) of anesthetized monkeys and middle temporal area (MT)
      of awake monkeys. Apparent motion consisted of multiple stationary stimulus
      flashes presented in sequence, characterized by their temporal separation (delta
      t) and spatial separation (delta x). Stimuli were 8 degrees square patterns of
      100% correlated random dots that moved at apparent speeds of 16 or 32 degrees/s.
      For both V1 and MT, the difference between the response to the preferred and null
      directions declined with increasing flash separation. For each neuron, we
      estimated the maximum flash separation for which directionally selective
      responses were observed. For the range of speeds we used, delta x provided a
      better description of the limitation on directional responses than did delta t.
      When comparing MT and V1 neurons of similar preferred speed, there was no
      difference in the maximum delta x between our samples from the two areas. In both
      V1 and MT, the great majority of neurons had maximal values of delta x in the
      0.25-1 degrees range. Mean values were almost identical between the two areas.
      For most neurons, larger flash separations led to both weaker responses to the
      preferred direction and increased responses to the opposite direction. The former
      mechanism was slightly more dominant in MT and the latter slightly more dominant
      in V1. We conclude that V1 and MT neurons lose direction selectivity for similar
      values of delta x, supporting the hypothesis that basic direction selectivity in
      MT is inherited from V1, at least over the range of stimulus speeds represented
      by both areas.

PMID- 15483065
TI  - Sound-localization performance in the cat: the effect of restraining the head.
AB  - In oculomotor research, there are two common methods by which the apparent
      location of visual and/or auditory targets are measured, saccadic eye movements
      with the head restrained and gaze shifts (combined saccades and head movements)
      with the head unrestrained. Because cats have a small oculomotor range
      (approximately +/-25 degrees), head movements are necessary when orienting to
      targets at the extremes of or outside this range. Here we tested the hypothesis
      that the accuracy of localizing auditory and visual targets using more
      ethologically natural head-unrestrained gaze shifts would be superior to head
      restrained eye saccades. The effect of stimulus duration on localization accuracy
      was also investigated. Three cats were trained using operant conditioning with
      their heads initially restrained to indicate the location of auditory and visual
      targets via eye position. Long-duration visual targets were localized accurately
      with little error, but the locations of short-duration visual and both long- and
      short-duration auditory targets were markedly underestimated. With the head
      unrestrained, localization accuracy improved substantially for all stimuli and
      all durations. While the improvement for long-duration stimuli with the head
      unrestrained might be expected given that dynamic sensory cues were available
      during the gaze shifts and the lack of a memory component, surprisingly, the
      improvement was greatest for the auditory and visual stimuli with the shortest
      durations, where the stimuli were extinguished prior to the onset of the eye or
      head movement. The underestimation of auditory targets with the head restrained
      is explained in terms of the unnatural sensorimotor conditions that likely result
      during head restraint.

PMID- 15483066
TI  - In vivo demonstration of a late depolarizing postsynaptic potential in CA1
      pyramidal neurons.
AB  - Previous studies have shown that GABA can have a depolarizing and excitatory
      action through GABA(A) receptors in mature CNS neurons in vitro. However, it
      remains unknown whether this occurs under physiological conditions. In this
      study, using intracellular recording and staining in vivo technique, we show a
      late depolarizing postsynaptic potential (L-PSP) in CA1 pyramidal neurons of
      adult Wistar rats under halothane anesthesia. This L-PSP was elicited in
      approximately 70% of the recorded neurons on stimulation of the Schaffer
      collaterals or the contralateral commissural path. The size of L-PSP was linearly
      correlated to the decay time constant but not the rising slope of the initial
      excitatory PSP (EPSP). Intravenous administration of the N-methyl-D-aspartate
      (NMDA) receptor blocker MK-801 and the GABA(A) receptor blocker picrotoxin
      significantly reduced the size of the L-PSP. The spine density and apical
      dendritic branching length of the neurons that displayed L-PSPs was significantly
      greater than those that do not. These results indicate that NMDA receptor and
      GABA(A) receptor-mediated depolarizing postsynaptic potentials can be revealed in
      CA1 pyramidal neurons of adult rats in vivo, supporting the physiological
      relevance of GABA(A)-mediated depolarization in normal neuronal information
      processing. The difference in electrophysiological properties and morphological
      features between neurons that display the L-PSP and the other neurons suggest
      that they might represent two different subtypes of CA1 pyramidal neurons.

PMID- 15483068
TI  - Contrast dependence of suppressive influences in cortical area MT of alert
      macaque.
AB  - Visual neurons are often characterized in terms of their tuning for various
      stimulus properties, such as shape, color, and velocity. Generally, these tuning
      curves are further modulated by the overall intensity of the stimulus, such that
      increasing the contrast increases the firing rate, up to some maximum. In this
      paper, we describe the tuning of neurons in the middle temporal area (MT or V5)
      of macaque visual cortex for moving stimuli of varying contrast. We find that,
      for some MT neurons, tuning curves for stimulus direction, speed, and size are
      shaped in part by suppressive influences that are present at high stimulus
      contrast but weak or nonexistent at low contrast. For most neurons, the
      suppression is direction-specific and strongest for large, slow-moving stimuli.
      The surprising consequence of this phenomenon is that some MT neurons actually
      fire more vigorously to a large low-contrast stimulus than to one of high
      contrast. These results are consistent with recent perceptual observations, as
      well as with information-theoretic models, which hypothesize that the visual
      system seeks to reduce redundancy at high contrast while maintaining sensitivity
      at low contrast.

PMID- 15483067
TI  - Early alcohol exposure induces persistent alteration of cortical columnar
      organization and reduced orientation selectivity in the visual cortex.
AB  - Fetal alcohol syndrome (FAS) is a major cause of learning and sensory deficits in
      children. The visual system in particular is markedly affected, with an elevated
      prevalence of poor visual perceptual skills. Developmental problems involving the
      neocortex are likely to make a major contribution to some of these abnormalities.
      Neuronal selectivity to stimulus orientation, a functional property thought to be
      crucial for normal vision, may be especially vulnerable to alcohol exposure
      because it starts developing even before eye opening. To address this issue, we
      examined the effects of early alcohol exposure on development of cortical neuron
      orientation selectivity and organization of cortical orientation columns. Ferrets
      were exposed to ethanol starting at postnatal day (P) 10, when the functional
      properties and connectivity of neocortical neurons start to develop. Alcohol
      exposure ended at P30, just before eye opening at P32. Following a prolonged
      alcohol-free period (15-35 days), long-term effects of early alcohol exposure on
      cortical orientation selectivity were examined at P48-P65, when orientation
      selectivity in normal ferret cortex has reached a mature state. Optical imaging
      of intrinsic signals revealed decreased contrast of orientation maps in alcohol-
      but not saline-treated animals. Moreover, single-unit recordings revealed that
      early alcohol treatment weakened neuronal orientation selectivity while
      preserving robust visual responses. These findings indicate that alcohol exposure
      during a brief period of development disrupts cortical processing of sensory
      information at a later age and suggest a neurobiological substrate for some types
      of sensory deficits in FAS.

PMID- 15483069
TI  - Nicotinic AChR in subclassified capsaicin-sensitive and -insensitive nociceptors
      of the rat DRG.
AB  - Nociceptive cells of the dorsal root ganglion (DRG) were subclassified, in vitro,
      according to patterns of voltage-activated currents. The distribution and form of
      nicotinic ACh receptors (nAChRs) were determined. nAChRs were present on both
      capsaicin-sensitive and -insensitive nociceptors but were not universally present
      in unmyelinated nociceptors. In contrast, all A delta nociceptors (types 4, 6,
      and 9) expressed slowly decaying nAChR. Three major forms of nicotinic currents
      were identified. Specific agonists and antagonists were used to demonstrate the
      presence of alpha7 in two classes of capsaicin-sensitive, unmyelinated
      nociceptors (types 2 and 8). In type 2 cells, alpha7-mediated currents were found
      in isolation. Whereas alpha7 was co-expressed with other nAChR in type 8 cells.
      These were the only classes in which alpha7 was identified. Other nociceptive
      classes expressed slowly decaying currents with beta4 pharmacology. Based on
      concentration response curves formed by nicotinic agonists [ACh, nicotine,
      dimethyl phenyl piperazinium (DMPP), cytisine] evidence emerged of two distinct
      nAChR differentially expressed in type 4 (alpha3beta4) and types 5 and 8
      (alpha3beta4 alpha5). Although identification could not be made with absolute
      certainty, patterns of potency (type 4: DMPP > cytisine > nicotine = ACh; type 5
      and type 8: DMPP = cytisine > nicotine = ACh) and efficacy provided strong
      support for the presence of two distinct channels based on an alpha3beta4
      platform. Studies conducted on one nonnociceptive class (type 3) failed to reveal
      any nAChR. After multiple injections of Di-I (1,1'-dilinoleyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate) into the hairy skin of the hindlimb, we
      identified cell types 2, 4, 6, 8, and 9 as skin nociceptors that expressed
      nicotinic receptors. We conclude that at least three nicotinic AChR are diversely
      distributed into discrete subclasses of nociceptors that innervate hairy skin.

PMID- 15483070
TI  - Processing of retinal and extraretinal signals for memory-guided saccades during
      smooth pursuit.
AB  - It is an essential feature for the visual system to keep track of self-motion to
      maintain space constancy. Therefore the saccadic system uses extraretinal
      information about previous saccades to update the internal representation of
      memorized targets, an ability that has been identified in behavioral and
      electrophysiological studies. However, a smooth eye movement induced in the
      latency period of a memory-guided saccade yielded contradictory results. Indeed
      some studies described spatially accurate saccades, whereas others reported
      retinal coding of saccades. Today, it is still unclear how the saccadic system
      keeps track of smooth eye movements in the absence of vision. Here, we developed
      an original two-dimensional behavioral paradigm to further investigate how smooth
      eye displacements could be compensated to ensure space constancy. Human subjects
      were required to pursue a moving target and to orient their eyes toward the
      memorized position of a briefly presented second target (flash) once it appeared.
      The analysis of the first orientation saccade revealed a bimodal latency
      distribution related to two different saccade programming strategies. Short
      latency (<175 ms) saccades were coded using the only available retinal
      information, i.e., position error. In addition to position error, longer-latency
      (>175 ms) saccades used extraretinal information about the smooth eye
      displacement during the latency period to program spatially more accurate
      saccades. Sensory parameters at the moment of the flash (retinal position error
      and eye velocity) influenced the choice between both strategies. We hypothesize
      that this tradeoff between speed and accuracy of the saccadic response reveals
      the presence of two coupled neural pathways for saccadic programming. A fast
      striatal-collicular pathway might only use retinal information about the flash
      location to program the first saccade. The slower pathway could involve the
      posterior parietal cortex to update the internal representation of the flash once
      extraretinal smooth eye displacement information becomes available to the system.

PMID- 15483071
TI  - Controlled substitution of soy protein for meat protein: effects on calcium
      retention, bone, and cardiovascular health indices in postmenopausal women.
AB  - In a controlled feeding study, the effects of substituting 25 g soy protein for
      meat on calcium retention and bone biomarkers were determined. Postmenopausal
      women (n = 13) ate two diets that were similar, except that, in one diet, 25 g
      high-isoflavone soy protein (SOY) was substituted for an equivalent amount of
      meat protein (control diet), for 7 wk each in a randomized crossover design.
      After 3 wk of equilibration, calcium retention was measured by labeling the 2-d
      menu with (47)Ca, followed by whole-body counting for 28 d. Urinary calcium and
      renal acid excretion were measured at wk 3, 5, and 7. Biomarkers of bone and
      cardiovascular health were measured at the beginning and end of each diet.
      Calcium was similarly retained during the control and SOY diets (d 28, percent
      dose, mean +/- pooled sd: 14.1 and 14.0 +/- 1.6, respectively). Despite a 15-20%
      lower renal acid excretion during the SOY diet, urinary calcium loss was
      unaffected by diet. Diet also did not affect any of the indicators of bone or
      cardiovascular health. Substitution of 25 g high isoflavone soy protein for meat,
      in the presence of typical calcium intakes, did not improve or impair calcium
      retention or indicators of bone and cardiovascular health in postmenopausal
      women.

PMID- 15483072
TI  - Separate measurement of plasma levels of acylated and desacyl ghrelin in healthy
      subjects using a new direct ELISA assay.
AB  - Two forms of ghrelin, acylated and desacyl, circulate in plasma. Although
      acylation is thought to be essential for ghrelin biological activities, recent
      studies have suggested that desacyl ghrelin may also possess biological activity.
      A new commercial ELISA system has now enabled us to measure plasma levels of each
      of these two ghrelin forms separately. This assay system directly measures levels
      using small amounts of plasma. To evaluate the utility of this assay system, we
      measured the plasma levels of the two forms of ghrelin in healthy volunteers.
      Although acylated ghrelin levels were equivalent to those measured previously by
      RIA, desacyl ghrelin levels were lower than those expected from the total ghrelin
      levels previously determined by RIA. The ratios of acylated to desacyl ghrelin
      significantly correlated with previously determined acylated, but not desacyl,
      ghrelin levels. After BMI adjustment, the levels of acylated, but not desacyl,
      ghrelin plasma levels were higher in female subjects than those in males. Several
      metabolic and hormonal parameters significantly correlated with either plasma
      acylated or desacyl ghrelin levels. These findings indicate that separate
      measurements of the two ghrelin form levels may provide valuable information on
      their structure, gender differences, and physiological implications.

PMID- 15483073
TI  - Growth hormone (GH) responses to GH-releasing hormone-arginine testing in human
      immunodeficiency virus lipodystrophy.
AB  - Prior studies suggest reduced overnight GH secretion in association with excess
      visceral adiposity among patients with HIV lipodystrophy (LIPO, i.e. with fat
      redistribution). We now investigate GH responses to standardized GHRH-arginine in
      LIPO patients (n = 39) in comparison with body mass index- and age-matched
      control groups [HIV patients without fat distribution (NONLIPO, n = 17)] and
      healthy subjects (C, n = 16). IGF-I [242 +/- 17; 345 +/- 38; 291 +/- 27 ng/ml (P
      < 0.05 vs. NONLIPO)] was lowest in the LIPO group. Our data demonstrate failure
      rates of 18% for the LIPO group vs. 5.9% for the NONLIPO group and 0% for the C
      group, using a stringent criterion of 3.3 ng/ml for peak GH response to GHRH
      arginine (P < 0.05 LIPO vs. C). Using less stringent cutoffs, the failure rate in
      the LIPO group rises to 38.5% at 7.5 ng/ml. Among the LIPO patients, the peak GH
      response to GHRH-arginine was significantly predicted by visceral adipose tissue
      (P = 0.008), free fatty acid (P = 0.04), and insulin level (P = 0.007) in
      regression modeling controlling for age, body mass index, sc fat area, and
      triglyceride level. These data demonstrate increased failure rates to
      standardized stimulation testing with GHRH-arginine in LIPO patients, in
      association with increased visceral adiposity. The effects of low-dose GH should
      be assessed in the large subset of LIPO patients with abnormal GH stimulation
      testing.

PMID- 15483074
TI  - Lean body mass is a major determinant of levothyroxine dosage in the treatment of
      thyroid diseases.
AB  - Total body weight is usually employed to calculate the amount of l-T(4) to be
      administered in patients with thyroid diseases. The aim of this study was to
      evaluate the effect of body composition on l-T(4) requirements. Body composition
      was assessed by dual energy x-ray absorptiometry in 75 patients on TSH
      suppressive l-T(4) therapy after conventional thyroid ablation for differentiated
      cancer. The mean daily dose of l-T(4) was lower in normal-weight (127.5 +/- 21.3
      mug/d) vs. overweight (139.4 +/- 24.5) and obese (151.3 +/- 29.1) subjects. There
      was a much stronger association between the l-T(4) dosage and lean body mass (P <
      0.001, r = 0.667) compared with fat mass (P = 0.023, r = 0.26). Measurement of
      regional tissue composition showed peripheral lean mass as the best correlate
      with the dose of l-T(4) (r = 0.679, P < 0.001) whereas no correlation was
      observed with peripheral fat mass. In conclusion, individual l-T(4) requirements
      are dependent on lean body mass. Age- and gender-related differences in l-T(4)
      needs reflect different proportions of lean mass over the total body weight. An
      estimate of lean mass may be helpful to shorten the time required to attain a
      stable dose of l-T(4), particularly in subjects with high body mass index values
      that may be due either to increased muscular mass or to obesity.

PMID- 15483075
TI  - A polymorphism in type I deiodinase is associated with circulating free insulin
      like growth factor I levels and body composition in humans.
AB  - The interaction between the GH-IGF-I axis and thyroid hormone metabolism is
      complex and not fully understood. T(4) stimulates IGF-I activity in animals in
      the absence of GH. On the other hand, GH replacement therapy results in an
      increase in serum T(3) and a decrease in T(4) and rT(3) levels, suggesting a
      stimulation of type I deiodinase (D1) activity. Recently, we demonstrated the
      association of two polymorphisms in D1 (D1a-C/T; T = 34%, and D1b-A/G; G = 10%)
      with serum iodothyronine levels. Haplotype alleles were constructed, suggesting a
      lower activity of the D1 haplotype 2 allele (aT-bA) and a higher activity of the
      haplotype allele 3 (aC-bG). In this study, we investigated whether genetic
      variations in D1 are associated with the IGF-I system. In 156 blood donors and
      350 elderly men, the association of the D1 haplotype alleles with circulating IGF
      I and free IGF-I levels was studied. In addition, potential associations with
      muscle strength and body composition were investigated in the elderly population.
      Finally, the relation between serum iodothyronine levels and IGF-I levels was
      studied. In blood donors, haplotype allele 2 was associated with higher levels of
      free IGF-I (302.9 +/- 22.9 vs. 376.3 +/- 19.1 pg/ml, P = 0.02). In elderly men,
      haplotype allele 2 also showed an allele dose increase in free IGF-I levels
      (P(trend) = 0.01) and an allele dose decrease in serum T(3) levels (P(trend) =
      0.01), independent of age. Carriers of the D1a-T variant also had a higher
      isometric grip strength (P = 0.047) and maximum leg extensor strength (P = 0.07)
      as well as a higher lean body mass (P = 0.03). In blood donors, T(4) and free
      T(4) were negatively correlated with total IGF-I levels (R = -0.18, P = 0.03 and
      R = -0.24, P = 0.003), whereas T(3) to T(4) and T(3) to reverse T(3) ratios were
      positively correlated with total IGF-I (R = 0.31, P < 0.001 and R = 0.18, P =
      0.03). Free IGF-I showed a negative correlation with T(4) (R = -0.26, P = 0.001)
      and T(4)-binding globulin (R = -0.31, P < 0.001) and a positive correlation with
      T(3) to T(4) ratio (R = 0.21, P = 0.01). In conclusion, a polymorphism that
      results in a decreased D1 activity is associated with an increase in free IGF-I
      levels. The pathophysiological significance of this association with IGF-I is
      supported by an increased muscle strength and muscle mass in carriers of the D1
      haplotype 2 allele in a population of elderly men. The association of D1
      haplotype allele 2 with serum T(3) levels in the elderly population suggests a
      relative increase in its contribution to circulating T(3) in old age.

PMID- 15483076
TI  - PPARgamma staining as a surrogate for PAX8/PPARgamma fusion oncogene expression
      in follicular neoplasms: clinicopathological correlation and histopathological
      diagnostic value.
AB  - The PAX8/PPARgamma (PPFP) fusion-oncogene is moderately specific for follicular
      thyroid carcinomas (FTC). It remains unknown whether this can be translated into
      improved diagnosis, classification, or outcome prediction. We studied a cohort of
      well-characterized follicular adenomas (FA), FTC, and Hurthle cell carcinomas
      (HCC) from patients with complete clinical follow-up, to determine whether
      PPARgamma immunohistochemistry (as a surrogate of PAX8/PPARgamma expression)
      helps to distinguish FA from FTC and to assess its diagnostic accuracy as an
      adjunct to frozen section. We also correlated PPARgamma staining with clinical
      outcomes to assess its role as a prognostic marker.PPARgamma staining was more
      common in FTC (31 of 54; 57%) than in HCC (one of 23; 4%) or FA (four of 31; 13%)
      (P < 0.000001). Adjunctive use of PPARgamma immunohistochemistry improved
      diagnostic sensitivity of intraoperative frozen section from 84% to 96% (P <
      0.05) but reduced specificity from 100% to 90% (P < 0.05). PPARgamma staining was
      associated with favorable prognostic indicators (female gender, better tumor
      differentiation, and lesser risk of metastases).PPARgamma staining may be helpful
      in the differential diagnosis of FA, FTC, and HCC, particularly when diagnostic
      sensitivity of histomorphology is reduced (e.g. during intraoperative frozen
      section). PPARgamma staining also shows an association with favorable prognosis
      and may have a role in risk stratification.

PMID- 15483077
TI  - The use of aldosterone-renin ratio as a diagnostic test for primary
      hyperaldosteronism and its test characteristics under different conditions of
      blood sampling.
AB  - Recent reviews recommended the use of the aldosterone/renin ratio (ARR) to screen
      for primary hyperaldosteronism. However, widely different cutoff levels have been
      proposed, and test characteristics of ARR under different conditions of sampling
      are not known. We conducted a retrospective review among 45 subjects with
      carefully validated diagnoses of primary hyperaldosteronism and 17 subjects with
      essential hypertension to study the utility of ARR. Sixty-two patients with 75
      sets of plasma renin activity (PRA), aldosterone, and ARR values from a postural
      study and 48 sets of values from a saline suppression test were analyzed. Ninety
      four percent of these subjects underwent investigations because of hypokalemic
      hypertension.ARR yielded larger areas under the curve in the receiver-operating
      characteristics curve than PRA or aldosterone under all conditions of testing.
      Our results confirmed the superiority of ARR to either aldosterone or PRA alone
      as a diagnostic test for primary hyperaldosteronism.ARR cutoff levels were
      significantly affected by the condition of testing. Depending on posture and time
      of day, it varied from 13.1-35.0 ng/dl per ng/ml.h in our study population. When
      using ARR for screening primary hyperaldosteronism, posture and time of sampling
      should be standardized both within and between centers to minimize variability in
      cutoff levels.

PMID- 15483078
TI  - Liddle's syndrome caused by a novel mutation in the proline-rich PY motif of the
      epithelial sodium channel beta-subunit.
AB  - Liddle's syndrome is an autosomal dominant form of salt-sensitive hypertension
      and has been shown to be caused by missense or frameshift mutations in the
      amiloride-sensitive epithelial sodium channel (ENaC), which is composed of three
      subunits: alpha, beta, and gamma. All disease mutations either remove or alter
      amino acids of the target proline-rich PPPxY sequence (PY motif) of beta- or
      gamma-ENaC and result in increased channel activity. In this report, we present a
      family with Liddle's syndrome whose abnormality is caused by a novel missense
      mutation, P616R, in the PY motif of the betaENaC. Functional studies using the
      P616R mutant expressed in Xenopus oocytes showed an approximately 6-fold increase
      in the amiloride-sensitive sodium channel activity compared with that of the wild
      type. These findings provide additional clinical evidence that a conserved PY
      motif is critically important for the regulation of ENaC activity.

PMID- 15483080
TI  - Variation of the McKusick-Kaufman gene and studies of relationships with common
      forms of obesity.
AB  - Obesity is a prominent feature of the Bardet-Biedl syndrome (BBS), one subset of
      which, BBS6, is due to mutations in the chaperonin-like gene termed the McKusick
      Kaufman syndrome (MKKS) gene. We tested whether variation in MKKS contributes to
      common and probably polygenic forms of obesity by performing mutation analysis of
      the coding region in 60 Danish white men with juvenile-onset obesity. Five
      variants were identified, including two synonymous mutations (Pro(39)Pro and
      Ile(178)Ile) and three nonsynonymous variants (Ala(242)Ser, Arg(517)Cys, and
      Gly(532)Val). Furthermore, the rare Ala(242)Ser was identified in two families
      and showed partial cosegregation with obesity. The Pro(39)Pro, Ile(178)Ile, and
      Arg(517)Cys variants are in complete linkage disequilibrium and defined a
      prevalent haplotype. In a case-control study, the Arg(517)Cys polymorphism allele
      prevalence was 11.4% [95% confidence interval (CI), 9.7-13.0] among 744 men with
      juvenile-onset obesity and 9.3% (CI, 7.9-10.7) among 867 control subjects (P =
      0.048). However, among middle-aged men the allelic prevalence was 9.7% (CI, 7.9
      11.4) among 523 obese men and 12.2% (CI, 10.8-13.6) among 1051 lean men (P =
      0.037). In conclusion, it is unlikely that MKKS variants play a major role in the
      pathogenesis of nonsyndromic obesity, although in rare cases the A242S allele may
      contribute to obesity.

PMID- 15483079
TI  - Short-term aromatase-enzyme blockade unmasks impaired feedback adaptations in
      luteinizing hormone and testosterone secretion in older men.
AB  - The mechanisms subserving hypoandrogenemia and relative hypogonadotropism in
      older men are not known. The present study tests the clinical hypothesis that
      aging impairs hypothalamopituitary adaptations to feedback withdrawal induced by
      antagonism of estrogen biosynthesis. To this end, we appraised gonadal axis
      responses to estrogen depletion induced by anastrozole (a potent and selective
      aromatase inhibitor) in nine older and 11 young men vs. placebo in 17 other older
      and eight young men. The study design comprised a prospectively randomized,
      double-blind, parallel-cohort intervention. To monitor LH release, blood was
      sampled every 10 min for 24 h; LH concentrations were assayed by two-site
      monoclonal immunoradiometric assay; pulsatile LH release quantitated by a model
      free discrete peak-detection technique (Cluster); feedback-dependent orderliness
      of LH secretion via the approximate entropy statistic; and 24-h rhythmicity of LH
      concentrations by cosine analysis. At baseline, older men had comparable
      estradiol and testosterone but lower LH concentrations than young controls.
      Exposure to anastrozole reduced (24-h pooled) serum estradiol concentrations by
      50% (P < 0.001) and elevated mean LH concentrations by 2.1-fold (P < 0.001) in
      both the young and older cohorts. However, older men failed to achieve young
      adult augmentation of the following: 1) total testosterone concentrations (P <
      0.01) or molar testosterone to SHBG ratios (P < 0.01); 2) incremental LH pulse
      amplitude (P < 0.001) and LH peak area (P < 0.01); 3) mean LH pulse frequency (P
      = 0.0044); and 4) quantifiable irregularity (approximate entropy) of LH release
      patterns (P < 0.001). FSH concentrations became comparable in the two age
      cohorts. In summary, administration of a potent and selective aromatase
      antagonist reduces estradiol and elevates mean LH concentrations equivalently in
      young and older men. The low estrogen-feedback state in elderly men unmasks
      diminished incremental LH pulse amplitude and area; absence of further
      acceleration of LH pulse frequency; impaired regulation of the orderliness of LH
      release; and reduced testosterone to SHBG ratios. Thus, aging alters expected
      hypothalamopituitary-gonadal adaptations to short-term partial estrogen depletion
      in healthy men.

PMID- 15483081
TI  - Resting metabolic rate and respiratory quotient in human longevity.
AB  - Significant changes in body composition, body fat distribution, and resting
      metabolic rate (RMR) occur with aging. Interestingly, studies on human longevity
      pointed out that long-lived subjects are less prone to the anthropometrics and
      metabolic derangement normally observed in the elderly. Indeed, the relationship
      between energy expenditure and longevity has been poorly investigated. Thus,
      energy expenditure parameters of 28 long-lived subjects were assessed and
      compared with those of 26 adults and 27 younger elderly. All subjects enrolled
      were female. In the whole population, RMR was negatively correlated with age (P <
      0.05), waist to hip ratio (WHR) (P < 0.001), fat mass (P < 0.001), and percent
      body fat (P < 0.03); respiratory quotient (Rq) displayed an age-related decrease
      (P < 0.001) and was negatively correlated with WHR (P < 0.001) and fat-free mass
      (FFM) (P < 0.006). In multivariate analysis, both RMR and Rq had FFM, WHR, but
      not body mass index as significant and independent determinants. Splitting the
      whole study group into subgroups according to age, long-lived subjects had oxygen
      volume, carbon dioxide volume, and Rq significantly higher than aged subjects but
      lower than adult subjects. In addition, long-lived subjects had total volume of
      expired air and RMR greater than aged subjects but not different from ones found
      in adults. In long-lived subjects, Rq was negatively correlated with percent body
      fat (P < 0.02), plasma glucose (P < 0.05), free fatty acid (P < 0.05), and WHR (P
      < 0.05), whereas RMR was negatively correlated with WHR (P < 0.05). No
      significant associations of RMR and Rq with FFM were found. In conclusion, our
      data demonstrate that human longevity seems protected toward an age-related
      decline. It is likely that the lack of the anthropometrics derangement may
      preserve long-lived subjects from the age-related decrease in energy metabolism.

PMID- 15483082
TI  - Insulin sensitivity and beta-cell function in protease inhibitor-treated and 
      naive human immunodeficiency virus-infected children.
AB  - Previous pediatric studies have failed to demonstrate a clear association between
      protease inhibitor (PI) therapy and abnormal glucose homeostasis in HIV-infected
      children. To define more precisely the impact of PI therapy on glucose
      homeostasis in this population, we performed the insulin-modified frequent
      sampling iv glucose tolerance test on 33 PI-treated and 15 PI-naive HIV-infected
      children. Other investigations included fasting serum lipids; glucose, insulin,
      and C-peptide; single-slice abdominal computed tomography; and, in a subset of PI
      treated children, an oral glucose tolerance test. There were no differences
      between the two groups with respect to fasting serum insulin or C-peptide,
      homeostatic model assessment insulin resistance, or quantitative insulin
      sensitivity check index. The mean insulin sensitivity index of PI-treated and PI
      naive children was 6.93 +/- 6.37 and 10.58 +/- 12.93 x 10(-4)min(-1) [microU/ml](
      1), respectively (P = 0.17). The mean disposition index for the two groups was
      1840 +/- 1575 and 3708 +/- 3005 x 10(-4)min(-1) (P = 0.013), respectively. After
      adjusting for potential confounding variables using multiple regression analysis,
      the insulin sensitivity index and disposition index of PI-treated children were
      significantly lower than that of PI-naive children (P = 0.01 for both). In PI
      treated but not PI-naive children, insulin sensitivity correlated inversely with
      visceral adipose tissue area (r = -0.43, P = 0.01) and visceral to sc adipose
      tissue ratio (r = -0.49, P = 0.004). Mildly impaired glucose tolerance was noted
      in four of 21 PI-treated subjects tested. Our results demonstrate not only that
      PI therapy reduces insulin sensitivity in HIV-infected children but also that it
      impairs the beta-cell response to this reduction in insulin sensitivity and, in a
      subset of children, leads to the development of impaired glucose tolerance. The
      presence of insulin resistance, dyslipidemia, and the significant correlation of
      reduced insulin sensitivity with increased visceral adipose tissue content
      suggest that PI-containing highly active antiretroviral therapy is associated
      with the emergence of early features of a metabolic syndrome-like phenotype.

PMID- 15483083
TI  - Adenoviral gene transfer allows Smad-responsive gene promoter analyses and
      delineation of type I receptor usage of transforming growth factor-beta family
      ligands in cultured human granulosa luteal cells.
AB  - In the human ovary, cell growth and differentiation are regulated by members of
      the TGF-beta superfamily, including growth differentiation factor-9 (GDF9), TGF
      beta, and activin. TGF-beta and activin are known to signal via Smad3 activation,
      and we have recently shown the involvement of Smad3 in cellular responses to
      GDF9. Recent studies with Smad3-deficient mice have also indicated a key role for
      this signaling mediator in ovarian folliculogenesis. We now demonstrate the use
      of a Smad3 reporter (CAGA-luciferase) adenovirus in primary cultures of human
      granulosa-luteal (hGL) cells to detect GDF9, TGF-beta, and activin responses. In
      rodent granulosa cells, TGF-beta and GDF9 signal through the TGF-beta type I
      receptor or activin receptor-like kinase 5 (Alk5), whereas the effect of activin
      is mediated though the activin type IB receptor, also known as Alk4. We now show
      that the GDF9 response in hGL cells is markedly potentiated upon overexpression
      of Alk5 by adenoviral gene transduction, as measured by the CAGA-luciferase
      reporter activity. A similar response to Alk5 overexpression was observed for TGF
      beta, but not for activin. Adenoviral overexpression of the activin type IB
      receptor Alk4 in hGL cells specifically potentiated activin signaling, but not
      GDF9 or TGF-beta signaling. Alk5 overexpression in hGL cells also potentiated the
      GDF9 response when inhibin B production was used as the read-out. These results
      indicate that the CAGA-luciferase adenovirus can be used to study Smad3 signaling
      in primary cultures of human cells, and that adenoviral overexpression of wild
      type receptors of the TGF-beta superfamily can be used to amplify the cellular
      response to ligands such as GDF9, TGF-beta, and activin. Furthermore, these
      studies indicate the involvement of Alk5 in GDF9 signaling in human cells and
      therefore, along with other recent studies, highlight how a limited number of
      type I and II receptors cooperate to generate specificity of action within the
      TGF-beta superfamily.

PMID- 15483084
TI  - Aging and estrogen effects on transcervical-transvaginal epithelial permeability.
AB  - The objective of the study was to understand age-related contributions of the
      resistance of the intercellular tight junctions (R(TJ)) and the resistance of the
      lateral intercellular space (R(LIS)) to the transcervical-transvaginal
      permeability. The experiments used normal human ectocervical epithelial cells
      obtained from women aged 36-65 yr. Twenty-four hours of treatment of cells with
      10 nm 17beta-estradiol decreased the R(LIS), whereas longer treatments were
      required to decrease The R(TJ). Aging had no effect on baseline or estrogen
      decrease in R(TJ), but it blocked both baseline and the estrogen decrease in
      R(LIS). Actin assays showed age-related decrease in the fraction of monomeric G
      actin and attenuation of sodium-nitroprusside-induced increase in G-actin. These
      results suggest that the aging-related diminished capacity of human ectocervical
      epithelial cells to remodel cellular actin from polymerized actin toward
      monomeric G-actin confers increased cell rigidity and therefore increased R(LIS).
      Therefore, the hypoestrogenism-related decrease in R(TJ) and the hypoestrogenism-
      and aging-related increase in R(LIS) could be the cellular mechanisms of
      decreased permeability that lead to decreased fluid transport and decreased
      lubrication of the lower genital tract in older postmenopausal women.

PMID- 15483085
TI  - Mifepristone is an effective oral alternative for the prevention of premature
      luteinizing hormone surges and/or premature luteinization in women undergoing
      controlled ovarian hyperstimulation for in vitro fertilization.
AB  - The present clinical study was conducted to investigate the effectiveness of a
      daily dose of 40 mg mifepristone in preventing premature LH surges in women
      undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization
      and to study the effect of this antiprogestin cotreatment on endometrial
      receptivity. This was a prospective, open-label, randomized, exploratory study in
      15 healthy volunteer oocyte donors who were randomly allocated to the
      experimental COH group, including mifepristone (group 1), or the control group,
      using a long protocol with GnRH agonists (group 2), in a ratio of 2:1, i.e. 10
      and five subjects, respectively. In group 1, human chorionic gonadotropin (hCG)
      was randomly administered (group 1A) or was withheld (group 1B) at the end of
      stimulation, so that two subgroups of five subjects each were formed, differing
      in the final oocyte maturation trigger. In all patients receiving mifepristone,
      50 mg progesterone were administered im at the time of hCG administration to
      counteract residual antiprogestogenic activity of mifepristone. Serum estradiol,
      progesterone (P), LH, and FSH levels were monitored in each patient on d 3 and 6
      and every 48 h thereafter. Endometrial biopsies were taken 2 and 7 d after hCG or
      P administration. Endometrial tissue was processed and evaluated in a blinded
      fashion for endometrial dating and quantitative PCR of at least four genes known
      to be up-regulated in receptive endometrium. The total FSH dose and duration of
      treatment in the two arms of the study were similar. The mean LH levels on d 6 of
      stimulation and the day of hCG/P treatment in the mifepristone group were 0.8 +/-
      0.7 and 0.5 +/- 0.6 mIU/ml, and those in control subjects were 2.4 +/- 3.8 and
      2.0 +/- 1.7 mIU/ml, respectively. No LH surges were observed in any subject
      treated with mifepristone. Serum P levels on the day of hCG/P were below the cut
      off level (1.2 ng/ml) in all subjects of the mifepristone group (range, <0.5 to
      1.05 ng/ml). The mean numbers of cumulus-oocyte complexes retrieved were 11.6 +/-
      6.6 and 19.6 +/- 11.8 in the subgroup treated with mifepristone and hCG and in
      the control group, respectively. The mean percentages of metaphase II, metaphase
      I, and germinal vesicle stage oocytes were 86.2, 6.9, and 3.4% in the
      mifepristone group and 68.4, 6.1, and 11.2% in the control group. In the
      mifepristone group that did not receive hCG and received P only at the end of
      stimulation, an endogenous LH surge was not observed nor were oocytes obtained.
      Histological evaluation of endometrial samples in patients treated with
      mifepristone and hCG (group 1A) confirmed normal development, whereas in patients
      treated with mifepristone only (group 1B), there was a complete arrest of the
      endometrial maturation. The expression patterns of glycodelin, IGF-binding
      protein-7, glutathione peroxidase-3, and solute carrier family 1 member 1 show a
      striking absence of up-regulation in patients treated with mifepristone (groups
      1A and 1B) compared with controls (group 2). The results of this exploratory
      study provide evidence that mifepristone is effective for the prevention of
      premature LH surges and/or premature luteinization in women undergoing COH for in
      vitro fertilization. However, endometrial receptivity status requires additional
      evaluation after decreasing RU-486 doses before this strategy can be considered
      as a new alternative to GnRH agonist/antagonist treatment.

PMID- 15483086
TI  - beta-Cell function in subjects spanning the range from normal glucose tolerance
      to overt diabetes: a new analysis.
AB  - The nature of the progressive beta-cell failure occurring as normal glucose
      tolerant (NGT) individuals progress to type 2 diabetes (T2DM) is incompletely
      understood. We measured insulin sensitivity (by a euglycemic insulin clamp) and
      insulin secretion rate (by deconvolution of plasma C-peptide levels during an
      oral glucose tolerance test) in 188 subjects [19 lean NGT (body mass index [BMI]
      </= 25 kg/m(2)), 42 obese NGT, 22 BMI-matched impaired glucose tolerance [IGT],
      and 105 BMI-matched T2DM]. Main determinants of beta-cell function on the oral
      glucose tolerance test were derived from a mathematical model featuring the
      following: 1) glucose concentration-insulin secretion dose response (glucose
      sensitivity), 2) a secretion component proportional to the derivative of plasma
      glucose concentration (rate sensitivity); and 3) a potentiation factor. When NGT
      and T2DM were subgrouped by 2-h plasma glucose concentrations, insulin secretion
      rate revealed an inverted U-shaped pattern, rising through NGT up to IGT and
      falling off thereafter. In contrast, beta-cell glucose sensitivity dropped in a
      monophasic, curvilinear fashion throughout the range of 2-h plasma glucose.
      Within the NGT range (2-h glucose of 4.1-7.7 mmol/liter), beta-cell glucose
      sensitivity declined by 50-70% (P < 0.02). Insulin sensitivity decreased sharply
      in the transition from lean to obese NGT and then declined further in IGT and
      mild T2DM to level off in the higher three quartiles of diabetic hyperglycemia.
      In T2DM, defective beta-cell potentiation and rate sensitivity also emerged (P
      </= 0.05). In the whole data set, insulin sensitivity and the dynamic parameters
      of beta-cell function explained 89% of the variability of 2-h plasma glucose
      levels. The following conclusions were reached: 1) beta-cell glucose sensitivity
      falls already within the NGT range in association with rising 2-h plasma glucose
      concentrations, although absolute insulin secretion rates increase; and 2)
      throughout the glucose tolerance range, dynamic parameters of beta-cell function
      (glucose sensitivity, rate sensitivity, and potentiation) and insulin sensitivity
      are independent determinants of 2-h plasma glucose levels.

PMID- 15483087
TI  - Increased cerebrospinal fluid levels of 3,3',5'-triiodothyronine in patients with
      Alzheimer's disease.
AB  - Cerebrospinal fluid (CSF) levels of rT(3) were evaluated in 21 euthyroid patients
      with overt Alzheimer's disease (AD) and 18 matched healthy controls. The
      assessment also included transthyretin and total T(3) and T(4) CSF
      concentrations. Despite normal circulating thyroid hormone levels, AD subjects
      showed significantly increased rT(3) levels and an increased rT(3) to T(4) ratio
      in the face of unchanged CSF total T(4) and transthyretin levels. These results
      suggest an abnormal intracerebral thyroid hormone metabolism and possibly the
      occurrence of brain hypothyroidism, either as a secondary consequence of the
      ongoing process or as a cofactor in the progression of the disease.

PMID- 15483088
TI  - Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial
      concentrations of plasma ghrelin, peptide YY, and insulin.
AB  - To help understand the mechanisms by which weight loss is maintained after Roux
      en-Y gastric bypass (RYGBP), we measured circulating concentrations of total and
      bioactive octanoylated ghrelin, peptide YY (PYY), glucose, and insulin in the
      fasted state and in response to a liquid test meal in three groups of adult
      women: lean (n = 8); weight-stable 35 +/- 5 months after RYGBP (n = 12; mean body
      mass index, 33 kg/m(2)); and matched to the surgical group for body mass index
      and age (n = 12). Fasting plasma total ghrelin levels were nearly identical
      between RYGBP (425 +/- 54 pg/ml) and the matched controls (424 +/- 28 pg/ml) and
      highest in lean controls (564 +/- 103 pg/ml). The response to the test meal was
      comparable between lean and RYGBP groups, with 27% and 20% maximal suppression,
      respectively, whereas the magnitude of suppression was significantly diminished
      in the matched controls (17%) compared with the lean group. Fasting levels of
      octanoylated ghrelin were highest in the lean controls, 220 +/- 36 pg/ml vs. 143
      +/- 27 in the RYGBP group (P = 0.05) and 127 +/- 12 pg/ml in the matched controls
      (P < 0.05). The magnitude of maximal postmeal suppression of octanoylated ghrelin
      was more marked than with total ghrelin, but similar among groups, ranging from
      44-47%. In response to the test meal, there was an early exaggerated rise in PYY
      in the RYGBP group, such that the peak PYY concentration was 163 +/- 24 pg/ml
      compared with 58 +/- 17 (P < 0.01) and 77 +/- 23 (P < 0.05) in the matched and
      lean controls, respectively; area under the curve at 90 min was significantly
      greater compared with both control groups. Leptin and fasting insulin
      concentrations and homeostasis model of assessment insulin resistance indices
      were nearly identical between lean and RYGBP subjects and significantly higher in
      the body mass index-matched controls. In summary, the absence of a compensatory
      increase in ghrelin concentrations that usually occurs with diet-induced weight
      loss, and the exaggerated postprandial PYY response after RYGBP, may contribute
      to weight loss and to the ability of an individual to maintain weight loss after
      this surgical procedure.

PMID- 15483089
TI  - Endocrine changes in full-term pregnancies and pregnancy loss due to energy
      restriction in the common marmoset (Callithrix jacchus).
AB  - Common marmosets, a New World primate, respond to a modest energy restriction
      with early termination of the pregnancy. Within female marmosets, comparisons (n
      = 6) between a normal, term pregnancy and a restriction-induced aborted pregnancy
      were used to establish cortisol, free estradiol, and chorionic gonadotropin (CG)
      as urinary markers of placental and fetal function under these two conditions.
      Abortions occurred 11-47 d after a 25% energy reduction during midpregnancy for
      all females. Cortisol concentrations were significantly lower in the last 2 wk
      for the restricted pregnancy than for matched samples in the normal term
      pregnancy. Both estradiol and estrone were examined in free and conjugated forms.
      Only free estradiol showed a significant reduction in mean concentrations during
      midpregnancy for the restricted females compared with their normal, term
      pregnancies. Mean CG levels from each female served as an independent marker of
      placental differentiation and function. CG levels were significantly lower during
      the 2 wk before abortion compared with matched days from a normal, term
      pregnancy. These data provide evidence that estradiol and cortisol are useful
      markers of placental and fetal viability in the common marmoset, and their
      reduced concentration following energy restriction suggests that restriction is
      not acting as a classical stressor by increasing cortisol and, subsequently,
      estradiol concentration.

PMID- 15483090
TI  - Interleukin-13 gene polymorphisms confer the susceptibility of Japanese
      populations to Graves' disease.
AB  - Graves' disease (GD) is an autoimmune disorder with genetic predisposition. IL-13
      is an important mediator of antiinflammatory immune responses and is expressed in
      the thyroid and orbit. The aim of the present study was to investigate whether IL
      13 gene polymorphisms are associated with the development of GD. IL-13 gene
      polymorphisms were studied in Japanese GD patients (n = 310) and healthy control
      subjects without antithyroid autoantibodies or a family history of autoimmune
      disorders (n = 244). A C/T polymorphism at position -1112 of the promoter region
      was measured using the direct sequencing method, and an Arg(130)Gln (G2044A)
      polymorphism in exon 4 was examined using the PCR-restriction fragment length
      polymorphism method. There was a significant decrease in -1112T allele frequency
      in GD patients compared with controls (16% vs. 23%; P = 0.0019). The frequency of
      the 2044A allele on exon 4 also appeared lower in GD patients compared with
      controls. Haplotype analysis showed a significant decrease in the -1112T/2044A
      haplotype in GD patients. There was no association between IL-13 gene
      polymorphisms and ophthalmopathy, severity, or serum IgE levels. In conclusion,
      IL-13 gene polymorphisms are associated with GD susceptibility in Japan.

PMID- 15483091
TI  - Plasma testosterone and sexual function in men receiving buprenorphine
      maintenance for opioid dependence.
AB  - High-dose methadone is well known to cause testosterone deficiency and sexual
      dysfunction in opioid-dependent men. Buprenorphine is a new drug for the
      pharmacotherapy of opioid dependence. Its influence on the gonadal axis has not
      been investigated to date. We therefore assayed testosterone, free testosterone,
      estradiol, SHBG, LH, FSH, and prolactin in 17 men treated with buprenorphine.
      Thirty-seven men treated with high-dose methadone and 51 healthy blood donors
      served as controls. Sexual function and depression were assessed using a self
      rating sexual function questionnaire and the Beck Depression Inventory. Patients
      treated with buprenorphine had a significantly higher testosterone level [5.1 +/-
      1.2 ng/ml (17.7 +/- 4.2 nmol/liter) vs. 2.8 +/- 1.2 ng/ml (9.7 +/- 4.2
      nmol/liter); P < 0.0001] and a significantly lower frequency of sexual
      dysfunction (P < 0.0001) compared with patients treated with methadone. The
      testosterone level of buprenorphine-treated patients did not differ from that of
      healthy controls. In conclusion, we demonstrated for the first time that
      buprenorphine, in contrast with high-dose methadone, seems not to suppress plasma
      testosterone in heroin-addicted men. To this effect, buprenorphine was less
      frequently related to sexual side effects. Buprenorphine might therefore be
      favored in the treatment of opioid dependence to prevent patients from the
      clinical consequences of methadone-induced hypogonadism.

PMID- 15483093
TI  - Localization and quantification of cyclic changes in the expression of endocrine
      gland vascular endothelial growth factor in the human corpus luteum.
AB  - Angiogenesis is essential for normal growth and function of the corpus luteum.
      The roles of various angiogenic factors in these events are being elucidated.
      Endocrine gland vascular endothelial growth factor (EG-VEGF) has recently been
      described in the human ovary. To define the localization of EG-VEGF mRNA in the
      corpus luteum and determine changes in its expression, dated human corpora lutea
      were studied at the early, mid-, and late luteal phases. Quantitative RT-PCR was
      employed to determine changes in EG-VEGF mRNA and compare expression to its
      related factor prokineticin-2 and the established angiogenic factor, VEGF. In
      situ hybridization was used to localize sites of production of EG-VEGF. To
      investigate whether expression of EG-VEGF was under the influence of LH or
      progesterone, luteinized granulosa cells were stimulated with human chorionic
      gonadotropin in the presence or absence of a progesterone synthesis inhibitor. EG
      VEGF mRNA increased throughout the luteal phase, whereas there was no change in
      VEGF mRNA. The relative abundance of RNAs based upon PCR signal intensity showed
      that VEGF and EG-VEGF were highly expressed, whereas expression of prokineticin-2
      was low. EG-VEGF mRNA was localized predominantly to granulosa-derived cells of
      the corpus luteum. Human chorionic gonadotropin stimulated both VEGF and EG-VEGF
      mRNA in vitro, but the level of expression was not influenced by progesterone.
      These results establish that in the human corpus luteum EG-VEGF is principally
      derived from granulosa lutein cells and that its synthesis is highest during the
      mid- to late luteal phase.

PMID- 15483092
TI  - Endocrine and immunogenetic testing in individuals with type 1 diabetes and 21
      hydroxylase autoantibodies: Addison's disease in a high-risk population.
AB  - Individuals with type 1 diabetes mellitus (T1D) at risk for Addison's disease
      (AD) can be identified with RIAs for autoantibodies to the adrenal antigen 21
      hydroxylase (21-OHAA). Screening individuals with T1D for 21OH-AA shows a
      relatively high prevalence of positive autoantibodies (1.4%, 38 of 2696
      subjects). After detection of 21-OHAA, individuals were evaluated with endocrine
      testing, including baseline cortisol, ACTH, and plasma renin activity and low (1
      mug) and high (250 mug) dose cortrosyn stimulation. Typing for DR and DQ alleles
      and for the major histocompatibility complex class I-related chain A (MICA) gene
      polymorphisms was performed. Six individuals were diagnosed with AD; five were
      identified on initial endocrine evaluation. Follow-up over 2.9 yr yielded one
      additional diagnosis of AD. Endocrine testing showed a correlation between
      baseline ACTH and peak cortisol (r = -0.61; P < 0.0001), baseline and peak
      cortisol (r = 0.70; P < 0.0001), and stimulated cortisol after low- and high-dose
      testing (r = 0.92; P < 0.0001). DR3-DQ2/DR4-DQ8 with DRB1* 0404 was associated
      with expression of 21-OHAA. At 2 yr, individuals homozygous for MICA5.1 had AD
      free survival of 60% compared with 100% AD-free survival in those who were not
      homozygous for MICA5.1. Homozygosity for MICA5.1 may increase progression to
      overt AD among 21-OHAA-positive individuals.

PMID- 15483094
TI  - Functional characterization of two novel point mutations in the CYP21 gene
      causing simple virilizing forms of congenital adrenal hyperplasia due to 21
      hydroxylase deficiency.
AB  - Congenital adrenal hyperplasia is a group of autosomal recessive disorders most
      often caused by deficiency of steroid 21-hydroxylase due to mutations in the
      CYP21 gene. We studied the functional and structural consequences of two novel
      missense mutations in the CYP21 gene, detected in two simple virilizing
      congenital adrenal hyperplasia patients. Both the male and female patient were
      compound heterozygous for the novel I77T and A434V point mutations, respectively.
      The in vitro expression analysis in COS-7 cells revealed a reduced 21-hydroxylase
      activity in the I77T mutant of 3 +/- 2% (sd) for the conversion of 17
      hydroxyprogesterone to 11-deoxycortisol and of 5 +/- 3% for the conversion of
      progesterone to 11-deoxycorticosterone. The A434V mutant had a residual enzyme
      activity of 14 +/- 2% for 17-hydroxyprogesterone and 12 +/- 6% for progesterone.
      Substrate affinity was similar in the mutants as in the CYP21 wild-type protein,
      whereas reaction velocity was markedly decreased in both mutants. These effects
      could be readily explained by structural changes induced by the mutations, which
      were rationalized by a three-dimensional-model structure of the CYP21 protein. We
      hypothesize that the I77T mutation markedly decreases the reaction product
      release and/or substrate entrance to the enzyme's active site, whereas the A434V
      mutant reduces both the catalytic capacity and reaction velocity. Studying the
      enzyme function in vitro helps to understand the phenotypical expression and
      disease severity of 21-hydroxylase deficiency and also provides new insights into
      cytochrome P450 structure-function relationships.

PMID- 15483095
TI  - Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with
      abnormal genitalia and/or impaired steroidogenesis: molecular and clinical
      studies in 10 patients.
AB  - We report on molecular and clinical findings in 10 Japanese patients (four males
      and six females) from eight families (two pairs of siblings and six isolated
      cases) with Antley-Bixler syndrome accompanied by abnormal genitalia and/or
      impaired steroidogenesis. Direct sequencing was performed for all the 15 exons of
      cytochrome P450 oxidoreductase gene (POR), showing two missense mutations (R457H
      and Y578C), a 24-bp deletion mutation resulting in loss of nine amino acids and
      creation of one amino acid (L612_W620delinsR), a single bp insertion mutation
      leading to frameshift (I444fsX449), and a silent mutation (G5G). R457H has
      previously been shown to be a pathologic mutation, and computerized modeling
      analyses indicated that the 15A>G for G5G could disturb an exonic splicing
      enhancer motif, and the remaining three mutations should affect protein
      conformations. Six patients were compound heterozygotes, and three patients were
      R457H homozygotes; no mutation was identified on one allele of the remaining one
      patient. Clinical findings included various degrees of skeletal features, such as
      brachycephaly, radiohumeral synostosis, and digital joint contractures in
      patients of both sexes, normal-to-poor masculinization during fetal and pubertal
      periods in male patients, virilization during fetal life and poor pubertal
      development without worsening of virilization in female patients, and relatively
      large height gain and delayed bone age from the pubertal period in patients of
      both sexes, together with maternal virilization during pregnancy. Blood
      cholesterol was grossly normal, and endocrine studies revealed defective CYP17A1
      and CYP21A2 activities. The results suggest that Antley-Bixler syndrome with
      abnormal genitalia and/or impaired steroidogenesis is caused by POR mutations,
      and that clinical features are variable and primarily explained by impaired
      activities of POR-dependent CYP51A1, CYP17A1, CYP21A2, and CYP19A1.

PMID- 15483096
TI  - Nutrient oxidation during moderately intense exercise in obese prepubertal boys.
AB  - The aim of this study was to measure the nutrient oxidation rate during walking
      at different speeds and to identify the walking speed associated with the highest
      fat oxidation rate in a group of prepubertal boys with different levels of
      adiposity. Twenty-four prepubertal boys (age, 10 +/- 1 yr) with different levels
      of overweight (body mass index, 25.5 +/- 3.5 kg/m(2); sd score of body mass
      index, 3.4 +/- 1.1) performed a treadmill test. We measured by indirect
      calorimetry their respiratory exchange while they walked at speeds of 4, 5, and 6
      km/h as well as their maximal oxygen uptake. The fat oxidation rate did not
      change significantly when the speed of walking was increased, whereas
      carbohydrate oxidation increased significantly (P < 0.001). A significant (P <
      0.05) association was found between adiposity (percent fat mass) and the fat to
      carbohydrate oxidation ratio during walking at 4, 5, and 6 km/h (r = 0.37, r =
      0.37, and r = 0.36, respectively), adjusting for exercise intensity (maximal
      oxygen uptake, percentage). The lowest fat to carbohydrate oxidation ratio, i.e.
      the highest fat oxidation/carbohydrate oxidation rate, was found at a walking
      speed of 4 km/h. Moderately intense exercise promoted the highest fat to
      carbohydrate oxidation ratio. Increasing the exercise intensity did not promote
      fat oxidation. Therefore, walking at a speed of 4 km/h is recommended as
      practicable exercise for obese boys and, consequently, for the treatment of
      childhood obesity.

PMID- 15483097
TI  - Sulfonylurea induced beta-cell apoptosis in cultured human islets.
AB  - Loss of beta-cell mass and function raises a concern regarding the application of
      sulfonylureas for the treatment of type 2 diabetes because previous studies have
      shown that agents that cause closure of inwardly rectifying K(+) sulfonylurea
      receptor subtype of ATP-sensitive potassium channels, such as tolbutamide and
      glibenclamide, induce apoptosis in beta-cell lines and rodent islets. Therefore,
      we investigated the effect of the new insulin secretagogues, repaglinide and
      nateglinide, and the sulfonylurea, glibenclamide, on beta-cell apoptosis in human
      islets. Human islets from six organ donors were cultured onto extracellular
      matrix-coated plates and exposed to glibenclamide, repaglinide, or nateglinide.
      The doses of the three compounds were chosen according to detected maximal
      effects, i.e. efficacy. Exposure of human islets for 4 h to 0.1 and 10 microm
      glibenclamide induced a 2.09- and 2.46-fold increase in beta-cell apoptosis,
      respectively, whereas repaglinide (0.01 and 1 microm) did not change the number
      of apoptotic beta-cells. At low concentration (10 microm), nateglinide did not
      induce beta-cell apoptosis. However, at high concentration of 1000 microm, it
      induced a 1.49-fold increase in the number of apoptotic beta-cells. Prolonged
      exposure for 4 d of the islets to the secretagogues induced beta-cell apoptosis.
      The increase was of 3.71- and 4.4-fold at 0.1 and 10 microm glibenclamide, 2.37-
      and 3.8-fold at 0.01 and 1 microm repaglinide, and of 3.2- and 4.6-fold at 10 and
      1000 microm nateglinide, respectively. Glibenclamide at 0.1-10 nm (doses that
      were less efficient on insulin secretion) did not induce beta-cell apoptosis
      after 4 h incubation as well as 0.1 nm after 4 d incubation. However, 1 and 10 nm
      glibenclamide for 4 d induced a 2.24- and 2.53-fold increase in beta-cell
      apoptosis, respectively. Taken together, closure of the inwardly rectifying K(+)
      sulfonylurea receptor subtype of ATP-sensitive potassium channels induces beta
      cell apoptosis in human islets and may precipitate the decrease in beta-cell mass
      observed in patients with type 2 diabetes.

PMID- 15483098
TI  - The increase of leukocytes as a new putative marker of low-grade chronic
      inflammation and early cardiovascular risk in polycystic ovary syndrome.
AB  - White blood cell (WBC) count is a known risk factor for atherosclerotic vascular
      disease in adult women. Polycystic ovary syndrome (PCOS) is potentially a risk
      factor for atherosclerosis and cardiovascular disease. The aim of the present
      study was to investigate leukocyte count in PCOS. One hundred and fifty PCOS
      women matched for age and body mass index with 150 healthy women were enrolled.
      WBC count, C-reactive protein, and a complete anthropometrical, metabolic, and
      hormonal evaluation were performed in both groups. Serum insulin, glucose level,
      and lipid profile were also measured in each subject. WBC count was significantly
      higher (P < 0.0001) in PCOS with (interquartile range in parentheses) 7260 (393)
      cells/mm(3), compared with controls with 5220 (210) cells/mm(3). C-reactive
      protein levels were significantly increased (P < 0.0001) in PCOS with 2 (1)
      mg/liter compared with healthy women with 0.7 (0.8) mg/liter. In both groups,
      there was a significant (P < 0.0001) linear correlation between WBC count and
      homeostasis model assessment score (PCOS, r = 0.94; controls, r = 0.91). Multiple
      linear regression analysis showed that other hormone levels are not predictors of
      leukocyte count both in PCOS and control women. In conclusion, our data
      demonstrate that PCOS women have an increased WBC count that correlates with
      homeostasis model assessment values.

PMID- 15483099
TI  - Skeletal muscle GLUT1 transporter protein expression and basal leg glucose uptake
      are reduced in type 2 diabetes.
AB  - To investigate the role of skeletal muscle tissue expression of the glucose
      transporter protein GLUT1 in mediating glucose disposal in the basal (fasting)
      state, skeletal muscle biopsies (vastus lateralis) were obtained from lean and
      obese nondiabetics and type 2 diabetic subjects. Basal and insulin-stimulated
      glucose uptakes were measured. Basal whole body glucose uptake was measured using
      isotope dilution, and arteriovenous catheterization limb balance was used to
      determine leg muscle glucose uptake. Basal (noninsulin-stimulated) whole body
      glucose uptake was higher in the type 2 group compared with the controls (2.26 +/
      0.17 vs. 1.83 +/- 0.15 mg/kg.min; P < 0.05). However, basal leg muscle glucose
      uptake was reduced in diabetic subjects (1.53 +/- 0.56 vs. 3.89 +/- 0.83 mg/100
      ml.min; P < 0.025) despite basal hyperglycemia (230 +/- 13 vs. 94 +/- 2 mg/dl; P
      < 0.0005). Skeletal muscle GLUT1 protein expression was lower in the type 2
      subjects (57 +/- 12 vs. 91 +/- 11 arbitrary units/10 microg protein; P < 0.05),
      although GLUT1 mRNA levels did not differ. In summary, 1) skeletal muscle tissue
      GLUT1 protein expression is reduced in type 2 diabetes and could contribute to
      impaired basal leg glucose uptake; and 2) elevated rates of basal whole body
      glucose uptake in type 2 diabetes are due to uptake in tissues other than
      skeletal muscle.

PMID- 15483100
TI  - P2Y12 receptors play a significant role in the development of platelet
      microaggregation in patients with diabetes.
AB  - Ninety-eight diabetic patients (type 2) were studied together with 24 healthy
      normotensive controls. Microaggregates (particle scale, <25 microm) of platelets
      were detected by a laser scattering system. Microaggregates in the control group
      showed a time-dependent reversible change; however, they existed continuously in
      82 of 98 diabetic patients. When platelets of diabetics were stimulated by a
      shear stress alone without ADP, 74 also showed spontaneous and irreversible
      microaggregates even though they were not observed in all control subjects. In
      control subjects, microaggregates were inhibited by MRS2279 (a P2Y1 antagonist),
      but not AR-C69931MX (a P2Y12 antagonist). However, AR-C69931MX prevented
      irreversible microaggregates in diabetic patients. When either aspirin or
      ticlopidine was administered to diabetic patients with irreversible
      microaggregates, both drugs significantly decreased microaggregates induced by a
      low dose of ADP. Ticlopidine additionally reduced the microaggregates induced by
      shear stress alone. In conclusion, microaggregates of platelets via P2Y12
      receptors could play a key role in the hypersensitivity of platelets in diabetic
      patients, and the measurement of microaggregation could be a useful marker to
      estimate of thrombogenesis. These findings present a possible new means for
      patients with diabetes to prevent ischemic events.

PMID- 15483101
TI  - Early human preantral follicles have relaxin and relaxin receptor (LGR7), and
      relaxin promotes their development.
AB  - The regulatory mechanisms of early follicle development are not clearly
      understood. Although relaxin is a peptide that controls cell proliferation and
      differentiation in many tissues, its role in human follicular development is
      unclear. In this study we cultured slices of human ovarian cortical tissue in the
      presence and absence of recombinant human relaxin. Ovarian tissue was obtained by
      biopsy during gynecological laparotomy or laparoscopy (14 women; mean age +/-
      sem, 29.0 +/- 6.1 yr; range, 17-37 yr). A significantly higher proportion of
      secondary follicles (14.5% vs. 5.0% in the control group; P < 0.01) and a
      significantly decreased proportion of primordial follicles (30.1% vs. 47.4% in
      the control group; P < 0.05) were found in tissues cultured with relaxin for 7 d.
      Immunocytochemical studies with the anti-C-peptide of prorelaxin and antirelaxin
      antibodies revealed the localization of relaxin in the oocyte and in flat
      pregranulosa and granulosa cells of primordial, primary, and secondary follicles.
      The presence of the relaxin receptor LGR7 was observed in flat pregranulosa and
      granulosa cells of primordial, primary, and secondary follicles by
      immunocytochemical and in situ hybridization analyses. These results suggest that
      relaxin plays a role through its receptor during the early stage of follicle
      development.

PMID- 15483102
TI  - Management of the nontoxic multinodular goiter in Latin America: comparison with
      North America and Europe, an electronic survey.
AB  - To assess diagnostic and therapeutic approaches to nontoxic multinodular goiter
      and to compare them with previously reported American Thyroid Association (ATA)
      and European Thyroid Association (ETA) surveys, an online questionnaire was
      distributed to Latin American Thyroid Society (LATS) members. An index case was
      presented (42-yr-old woman with an enlarged, irregular, nontender, 50- to 80-g
      thyroid and no clinical suspicion of malignancy or dysfunction), and 11
      variations were proposed to evaluate how each alteration would affect management.
      We obtained 148 responses (response rate, 50%). In the index case, the most used
      blood tests were TSH (96%), antithyroid peroxidase antibodies (76%), and free
      T(4) (64%); 5% included a calcitonin assay. Nearly 90% would perform ultrasound,
      and only 16% used scintigraphy. Fine needle biopsy was indicated by 88%, with
      ultrasound guidance in 75% of times. For treatment, observation was preferred by
      39%, surgery by 28%, levothyroxine by 21%, and radioiodine by 7% (60% with
      recombinant TSH prestimulation). A suppressed TSH level prompted 45% of the
      respondents to recommend radioiodine, whereas 70-78% indicated surgery in the
      presence of a large goiter or suspicion of malignancy. In conclusion, no
      consensus exists concerning the ideal management of nontoxic goiter among LATS
      members, in agreement with previous ATA and ETA surveys. Levothyroxine therapy is
      less used by LATS than by ATA or ETA members, and a more aggressive therapeutic
      strategy is generally preferred by members of LATS and ETA compared with ATA.

PMID- 15483103
TI  - Distinct regulation of cyclooxygenase-2 by interleukin-1beta in normal and
      endometriotic stromal cells.
AB  - Aberrant production of cyclooxygenase-2 (COX-2) plays pivotal roles in many
      pathological processes including tumorigenesis and endometriosis, although the
      underlying mechanism remains obscure. Herein we report evidence to demonstrate
      that COX-2 is distinctly regulated by IL-1beta in normal and endometriotic
      stroma. Ectopic endometriotic stromal cell is at least 100 times more sensitive
      to IL-1beta treatment, compared with its eutopic counterpart. Induction of COX-2
      expression in normal endometrial stroma by IL-1beta is primary due to enhancement
      of COX-2 mRNA stability. In contrast, IL-1beta not only increases COX-2 mRNA
      stability but also up-regulates COX-2 promoter activity in ectopic endometriotic
      stroma. Induction of COX-2 promoter activity by IL-1beta is mediated via MAPK
      dependent phosphorylation of cAMP-responding element binding protein. Promoter
      activity and EMSAs demonstrate that a cAMP response element site located at -571/
      564 of COX-2 promoter is critical for IL-1beta-induced COX-2 gene expression. Our
      results indicate that elevation of COX-2 expression in endometriotic tissues may
      result from increased sensitivity to proinflammatory cytokines such as IL-1beta,
      which is consistently present in the peritoneal fluid of endometriosis patients.
      Distinct regulation of COX-2 gene by IL-1beta may play a critical role in
      pathophysiological processes such as cancer formation and endometriosis.

PMID- 15483104
TI  - Dominant transmission of prepubertal gynecomastia due to serum estrone excess:
      hormonal, biochemical, and genetic analysis in a large kindred.
AB  - Increased extraglandular aromatization has been reported to cause the rare entity
      of familial gynecomastia. Recently heterozygous inversions at the p450 aromatase
      gene promotor locus were detected in two different families with this syndrome.
      We studied a family in which seven affected males over three generations had
      inherited prepubertal gynecomastia in an autosomal dominant manner. The proband
      developed gynecomastia at 11.5 yr, entered puberty at 12.5 yr, but was
      incompletely virilized at 19 yr. A similar development was observed in his
      affected stepbrother and one first-degree cousin. All three boys had acceleration
      of prepubertal growth and bone age. The older two had a diminished pubertal
      growth spurt and precocious growth arrest, but their final heights were within
      the range of their target height. In addition, the maternal grandfather and three
      maternal uncles were affected, who all had been mastectomized. The mother of the
      proband had normal age at menarche and no macromastia. Estrone levels of the
      proband and the other affected boys were elevated, 17beta-estradiol levels were
      high-normal, and testosterone levels were low. Hormonal analyses of the affected
      adults, who had all fathered children, revealed pathologically low serum
      testosterone levels but normal to high-normal levels of estradiol and estrone.
      The mother of the proband had elevated estrone levels. Treatment of the proband
      was more effective with anastrozole than with testolactone and increased the
      initially reduced testes volume to normal size, promoted virilization, and
      normalized serum estrone and testosterone levels. Neither preadipocytes from
      breast fat tissue of the affected stepbrother nor peripheral lymphocytes of the
      affected boys exhibited increased aromatase activity in culture. Therefore, these
      cells can be excluded from being the source of estrone excess. In addition, serum
      of the proband and his stepbrother did not contain factors promoting aromatase
      activity as assayed using preadipocytes from control individuals.A repeat
      polymorphism of the p450 aromatase gene cosegregated with the disease phenotype
      in the family, making a mutation of the p450 aromatase gene likely. Single-strand
      conformational polymorphism analysis of the known alternative untranslated exons
      and all coding exons of the p450 aromatase gene did not indicate any mutation. In
      addition, fluorescent in situ hybridization analysis using four probes covering
      the promotor region did not reveal the presence of any major inversion at this
      locus. In conclusion, preadipocytes and blood cells were excluded as the cell
      source of increased aromatization. Fluorescent in situ hybridization and single
      strand conformational polymorphism analyses did not reveal any mutation of the
      p450 aromatase gene, but an intragenic polymorphic marker cosegregated with the
      disease phenotype. Excess of serum estrone in the presence of normal 17beta
      estradiol levels may be the only indicative serum parameter of this mild
      manifestation of aromatase excess syndrome, which includes prepubertal
      gynecomastia and moderate hypogonadism in men but not necessarily short stature.
      In women, this mode of aromatase excess may remain clinically inapparent.

PMID- 15483105
TI  - Flutamide-metformin plus ethinylestradiol-drospirenone for lipolysis and
      antiatherogenesis in young women with ovarian hyperandrogenism: the key role of
      metformin at the start and after more than one year of therapy.
AB  - Flutamide (Flu)-metformin (Met) with ethinylestradiol-drospirenone is a
      combination therapy that reduces the total and abdominal fat excess, diminishes
      the lean mass deficit, and attenuates the dysadipocytokinemia of young and
      nonobese women with ovarian hyperandrogenism, a variant of polycystic ovary
      syndrome. We have now questioned the need: 1) to add Met at the start of Flu plus
      ethinylestradiol-drospirenone; and 2) to maintain Met after more than 1 yr on
      full combination therapy. The additive effects of Met (850 mg/d) were assessed in
      studies A and B, over 3 months, in young patients with hyperinsulinemic
      hyperandrogenism. In study A, all participants [n = 31; age approximately 16 yr;
      body mass index approximately 22 kg/m(2)] started on Flu (62.5 mg/d) and an oral
      contraceptive (ethinyl-estradiol + drospirenone), and they were randomized to
      receive Met in addition or not. In study B, all participants (n = 42; age
      approximately 19 yr; body mass index approximately 22 kg/m(2)) had been treated
      with Flu-Met plus the same contraceptive for a mean duration of 17 months, and
      they were randomized for discontinuation of Met or not. Fasting blood glucose,
      serum insulin, testosterone, lipid profile, adiponectin, and IL-6 were determined
      at the start and after 3 months, together with body composition, by dual energy x
      ray absorptiometry. The results of studies A and B complemented each other; the
      addition of Met was found to have consistently (more) normalizing effects on IL-6
      and adiponectin, on lean mass (mean Met benefit of +1.2 kg in study A and +0.6 kg
      in study B), and in particular on abdominal fat excess [Met benefit of -0.7 kg
      (A) and -0.3 kg (B)]. In conclusion, Met proved to be a pivotal component of a
      prime combination therapy that attenuates the dysadipocytokinemia, the lean mass
      deficit, and the central adiposity of young patients with polycystic ovary
      syndrome.

PMID- 15483106
TI  - Effects of rosiglitazone in obese women with polycystic ovary syndrome and severe
      insulin resistance.
AB  - Our objective was to evaluate the effectiveness of the insulin-sensitizing agent
      rosiglitazone in obese women with polycystic ovary syndrome (PCOS) and severe
      insulin resistance. Twelve obese women with PCOS were recruited. All were hirsute
      and anovulatory with acanthosis nigricans indicating severe insulin resistance.
      All women were treated with 4 mg of rosiglitazone daily for 6 months. A standard
      75-g oral glucose tolerance test with insulin levels was performed before and
      after the women were treated with rosiglitazone. Glucose and insulin areas under
      the curve (AUC) were calculated. Serum levels of total and free testosterone,
      dehydroepiandrosterone sulfate, LH, and 17-hydroxyprogesterone were also measured
      before and after treatment. The body mass index was determined before and after
      treatment. There was a highly significant (r = 0.881, P < 0.0001) positive
      correlation between insulin response during oral glucose tolerance test and basal
      total testosterone levels. After treatment with rosiglitazone, there were
      significant decreases in fasting insulin levels (46.0 +/- 6.5 vs. 16.9 +/- 2.0
      microU/ml; P < 0.001), insulin AUC (749.3 +/- 136.3 vs. 225.0 +/- 15.7 microU/ml;
      P = 0.003), fasting glucose levels (90.8 +/- 3.0 vs. 81.8 +/- 1.9 mg/dl; P =
      0.003), and glucose AUC (437.9 +/- 25.0 vs. 322.5 +/- 14.7 mg/dl; P < 0.001).
      Both total testosterone (96.3 +/- 17.3 vs. 56.1 +/- 5.8 ng/dl; P = 0.01) and free
      testosterone (5.8 +/- 0.6 vs. 3.4 +/- 0.5 pg/ml; P < 0.001) decreased
      significantly after treatment, although there was no significant change in LH
      levels. Levels of SHBG increased significantly (18.3 +/- 3.4 vs. 25.8 +/- 6.6
      nmol/liter; P = 0.009) after treatment, and dehydroepiandrosterone sulfate levels
      decreased significantly (P = 0.04). There was no significant change in body mass
      index (40.4 +/- 2.4 vs. 41.1 +/- 2.7 kg/m(2)). Eleven of the women reverted to
      regular ovulatory cycles during the treatment period. We conclude that 1)
      rosiglitazone therapy improves insulin resistance and glucose tolerance in obese
      women with PCOS; 2) rosiglitazone decreases ovarian androgen production, which
      appears to be independent of any changes in LH levels; 3) hyperinsulinemia
      appears to play a key role in the overproduction of ovarian androgens in these
      women because attenuation of insulin levels is associated with decreased
      testosterone levels; and 4) short-term rosiglitazone therapy helps restore
      spontaneous ovulation.

PMID- 15483107
TI  - Impaired production of gastric ghrelin in chronic gastritis associated with
      Helicobacter pylori.
AB  - Ghrelin is primarily secreted from the stomach and has been implicated in the
      coordination of eating behavior and weight regulation. The effects of
      Helicobacter pylori infection on plasma ghrelin concentration and gastric ghrelin
      production still have not been well known. We determined plasma ghrelin
      concentration in a total of 160 consecutive individuals with normal body mass
      index including 110 H. pylori-infected and 50 H. pylori-negative subjects. The
      expression levels of ghrelin mRNA and ghrelin-producing cells in the gastric
      mucosa were quantified with real-time quantitative RT-PCR and
      immunohistochemistry, respectively. The severity of gastric atrophy was evaluated
      by serum pepsinogen concentrations. Plasma ghrelin concentration, gastric ghrelin
      mRNA, and ghrelin-positive cell numbers in gastric mucosa were significantly
      lower in H. pylori-infected subjects. The decrease in plasma ghrelin
      concentration in H. pylori-positive subjects was accompanied by an attenuation of
      ghrelin mRNA expression and a reduction of ghrelin-positive cell numbers in the
      gastric mucosa. Moreover, lower serum pepsinogen I concentrations and I/II ratio
      were significantly associated with lower plasma ghrelin concentrations in H.
      pylori-positive subjects. These findings suggest that impaired gastric ghrelin
      production in association with atrophic gastritis induced by H. pylori infection
      accounts for the decrease in plasma ghrelin concentration.

PMID- 15483109
TI  - Preserving properties of object shape by computations in primary visual cortex.
AB  - Although our visual system is extremely good at extracting objects from the
      visual scene, this process involves complicated computations that are thought to
      require image processing by many successive cortical areas. Thus, intermediate
      stages in object extraction should not eliminate essential properties of the
      objects that are still required by later stages. A particularly important
      characteristic of an object is its shape, and shape has the property that it is
      unchanged by translations, rotations, and magnifications of the image. I show
      that the requirement for this property of shape to be preserved in the image, as
      represented by the firing of neurons in the primary visual cortex (V1), is
      equivalent to a particular type of computation, known as a wavelet transform,
      determining the firing rate of V1 neurons in response to an image on the retina.
      Experimental data support the conclusion that the neural representation of images
      in V1 is described by a wavelet transform and, therefore, that the properties of
      shape are preserved.

PMID- 15483108
TI  - Dysregulation of the fibroblast growth factor system in major depression.
AB  - In this report we describe findings that imply dysregulation of several
      fibroblast growth factor (FGF) system transcripts in frontal cortical regions of
      brains from human subjects with major depressive disorder (MDD). This altered
      gene expression was discovered by microarray analysis of frontal cortical tissue
      from MDD, bipolar, and nonpsychiatric control subjects and was verified by
      quantitative real-time PCR analysis and, importantly, in a separate cohort of MDD
      subjects. Furthermore, we show, through a separate analysis of specific serotonin
      reuptake inhibitor (SSRI)-treated and non-SSRI-treated MDD subjects that the
      observed changes in expression of FGF transcripts are not secondary to drug
      treatment. Rather, changes in specific FGF transcripts are attenuated by SSRIs
      and may thus be partially responsible for the mechanism of action of these drugs.
      We also make available the gene-expression profile of all of the other growth
      factors and growth factor receptors detected in these postmortem samples.

PMID- 15483110
TI  - Fgf8 regulates the development of intra-neocortical projections.
AB  - The process of generating functionally distinct neocortical areas requires the
      formation of an intra-neocortical connectivity map. Here, we explore the early
      development of murine intra-neocortical projections and find that axons from
      rostral and caudal neurons remain, respectively, within large rostral and caudal
      domains of the neonatal neocortex. Despite evidence that thalamic input can
      regulate neocortical areal properties, we found that the neonatal intra
      neocortical projection pattern was not perturbed when thalamic input was absent
      in Gbx2 mutants. On the contrary, in Fgf8 hypomorphic mutants, the rostral
      neocortex of which acquires more caudal molecular properties, caudally located
      neurons ectopically project axons into the rostral cortex. Therefore, neocortical
      patterning by Fgf8 also contributes to arealization through mediating early
      development of intra-neocortical connectivity.

PMID- 15483111
TI  - Intrastriatal transforming growth factor alpha delivery to a model of Parkinson's
      disease induces proliferation and migration of endogenous adult neural progenitor
      cells without differentiation into dopaminergic neurons.
AB  - We examined the cell proliferative, neurogenic, and behavioral effects of
      transforming growth factor alpha (TGFalpha) in a 6-OHDA Parkinson's disease model
      when compared with naive rats. Intrastriatal TGFalpha infusion induced
      significant proliferation, hyperplastic nodules, and substantial migratory waves
      of nestin-positive progenitor cells from the adult subventricular zone (SVZ) of
      dopamine-denervated rats. Interestingly, SVZ cells in naive rats displayed
      proliferation but minimal migration in response to the TGFalpha infusion. The
      cells in the expanded SVZ accumulated cytoplasmic beta-catenin, indicating
      activation of classical Wnt signaling. However, no evidence of any neuronal
      differentiation was found of these recruited progenitor cells anywhere examined
      in the brain. Consequently, no evidence of dopaminergic (DA) neurogenesis was
      found in the striatum or substantia nigra in any experimental group, and
      amphetamine-induced behavioral rotations did not improve. In summary, the cells
      in the TGFalpha-induced migratory cellular wave remain undifferentiated and do
      not differentiate into midbrain-like DA neurons.

PMID- 15483112
TI  - Differential control of synaptic and ectopic vesicular release of glutamate.
AB  - Exocytosis of synaptic vesicles occurs not only at synaptic active zones but also
      at ectopic sites. Ectopic exocytosis provides a direct and rapid mechanism for
      neurons to communicate with glia that does not rely on transmitter spillover from
      the synaptic cleft. In the cerebellar cortex the processes of Bergmann glia cells
      encase synapses between presynaptic climbing fiber varicosities and postsynaptic
      Purkinje cell spines and express both AMPA receptors and electrogenic glutamate
      transporters. AMPA receptors expressed by Purkinje cells and Bergmann glia cells
      are activated predominantly by synaptic and ectopic release, respectively, and
      therefore can be used to compare the properties of the two release mechanisms. We
      report that vesicular release differs at synaptic and ectopic sites in the
      magnitude of short-term plasticity and the proportions of Ca2+ channel subtypes
      that trigger glutamate release. High-affinity glutamate transporter-mediated
      currents in Bergmann glia cells follow the rules of synaptic release more closely
      than the rules of ectopic release, indicating that the majority of glutamate is
      released from conventional synapses. On the other hand, ectopic release produces
      high-concentration glutamate transients at Bergmann glia cell membranes that are
      necessary to activate low-affinity AMPA receptors rapidly. Ectopic release may
      provide a geographical cue to guide Bergmann glia cell membranes to surround
      active synapses and ensure efficient uptake of glutamate that diffuses out of the
      synaptic cleft.

PMID- 15483114
TI  - Excessive expression of acetylcholinesterase impairs glutamatergic synaptogenesis
      in hippocampal neurons.
AB  - Acetylcholinesterase (AChE) exerts noncatalytic activities on neural cell
      differentiation, adhesion, and neuritogenesis independently of its catalytic
      function. The noncatalytic functions of AChE have been attributed to its
      peripheral anionic site (PAS)-mediated protein-protein interactions.
      Structurally, AChE is highly homologous to the extracellular domain of
      neuroligin, a postsynaptic transmembrane molecule that interacts with presynaptic
      beta-neurexins, thus facilitating synaptic formation and maturation. Potential
      effects of AChE expression on synaptic transmission, however, remain unknown.
      Using electrophysiology, immunocytochemistry, and molecular biological
      approaches, this study investigated the role of AChE in the regulation of
      synaptic formation and functions. We found that AChE was highly expressed in
      cultured embryonic hippocampal neurons at early culture days, particularly in
      dendritic compartments including the growth cone. Subsequently, the expression
      level of AChE declined, whereas synaptic activity and synaptic proteins
      progressively increased. Chronic blockade of the PAS of AChE with specific
      inhibitors selectively impaired glutamatergic functions and excitatory synaptic
      structures independently of cholinergic activation, while inducing AChE
      overexpression. Moreover, the PAS blockade-induced glutamatergic impairments were
      associated with a depressed expression of beta-neurexins and an accumulation of
      other synaptic proteins, including neuroligins, and were mostly preventable by
      antisense suppression of AChE expression. Our findings demonstrate that
      interference with the nonenzymatic features of AChE alters AChE expression, which
      impairs excitatory synaptic structure and functions.

PMID- 15483113
TI  - Cortical GABA interneurons in neurovascular coupling: relays for subcortical
      vasoactive pathways.
AB  - The role of interneurons in neurovascular coupling was investigated by patch
      clamp recordings in acute rat cortical slices, followed by single-cell reverse
      transcriptase-multiplex PCR (RT-mPCR) and confocal observation of biocytin-filled
      neurons, laminin-stained microvessels, and immunodetection of their afferents by
      vasoactive subcortical cholinergic (ACh) and serotonergic (5-HT) pathways. The
      evoked firing of single interneurons in whole-cell recordings was sufficient to
      either dilate or constrict neighboring microvessels. Identification of vasomotor
      interneurons by single-cell RT-mPCR revealed expression of vasoactive intestinal
      peptide (VIP) or nitric oxide synthase (NOS) in interneurons inducing dilatation
      and somatostatin (SOM) in those eliciting contraction. Constrictions appeared
      spatially restricted, maximal at the level of neurite apposition, and were
      associated with contraction of surrounding smooth muscle cells, providing the
      first evidence for neural regulation of vascular sphincters. Direct perfusion of
      VIP and NO donor onto the slices dilated microvessels, whereas neuropeptide Y
      (NPY) and SOM induced vasoconstriction. RT-PCR analyses revealed expression of
      specific subtypes of neuropeptide receptors in smooth muscle cells from
      intracortical microvessels, compatible with the vasomotor responses they
      elicited. By triple and quadruple immunofluorescence, the identified vasomotor
      interneurons established contacts with local microvessels and received, albeit to
      a different extent depending on interneuron subtypes, somatic and dendritic
      afferents from ACh and 5-HT pathways. Our results demonstrate the ability of
      specific subsets of cortical GABA interneurons to transmute neuronal signals into
      vascular responses and further suggest that they could act as local integrators
      of neurovascular coupling for subcortical vasoactive pathways.

PMID- 15483115
TI  - Presynaptic glycine receptors on GABAergic terminals facilitate discharge of
      dopaminergic neurons in ventral tegmental area.
AB  - GABA-mediated postsynaptic currents (IPSCs) were recorded from dopaminergic (DA)
      neurons of the ventral tegmental area (VTA) of rats, in acute brain slices, and
      from enzymatically or mechanically dissociated neurons. In young rats (3-10 d of
      age), where GABA is excitatory, glycine (1-3 microm) and taurine (10-30 microm)
      increased the amplitude of evoked IPSCs (eIPSCs) and the frequency of spontaneous
      IPSCs (sIPSCs) but had minimal postsynaptic effects. Strychnine (1 microm)
      blocked the action of glycine; when applied alone, it reduced the amplitude of
      eIPSCs and the frequency of sIPSCs, indicating a tonic facilitation of GABAergic
      excitation by some endogenous glycine agonist(s). In medium containing no Ca2+,
      or with Cd2+ or tetrodotoxin added, the amplitude and especially the frequency of
      sIPSCs greatly diminished. In many cells, glycine had no effect on remaining
      miniature IPSCs, suggesting a preterminal site of glycine receptors (GlyRs). Fura
      2 fluorescent imaging showed a glycine-induced increase of [Ca2+] in nerve
      terminals (on DA neurons), which was suppressed by strychnine or 3 microm omega
      conotoxin MVIIA. Therefore, the presynaptic GlyR-mediated facilitation of
      GABAergic transmission seems to be mediated by N- and/or P/Q-type Ca2+ channels.
      In older rats (22-30 d of age), where GABA causes inhibition, the effect of
      strychnine on GABAergic IPSCs was reversed to facilitation, indicating a tonic
      glycinergic inhibition of GABA release. Furthermore, glycine (1-3 microm) reduced
      the amplitude of eIPSCs and the frequency of sIPSCs. Hence, the overall effect of
      the presynaptic action of glycine is to enhance the firing of DA cells, both in
      very young and older rats.

PMID- 15483116
TI  - Retinotopic organization and functional subdivisions of the human lateral
      geniculate nucleus: a high-resolution functional magnetic resonance imaging
      study.
AB  - Functional magnetic resonance imaging (fMRI) has provided intriguing insights
      into the topography and functional organization of visual cortical areas in the
      human brain. However, little is known about the functional anatomy of subcortical
      nuclei. Here, we used high-resolution fMRI (1.5 x 1.5 x 2 mm3) at 3 tesla to
      investigate the retinotopic organization of the human lateral geniculate nucleus
      (LGN). The central 15 degrees of the visual field were mapped using periodic
      flickering checkerboard stimuli that evoked a traveling wave of activity. The
      contralateral visual hemifield was represented with the lower field in the medial
      superior portion and the upper field in the lateral-inferior portion of each LGN.
      The horizontal meridian was significantly overrepresented relative to the
      vertical meridian. The fovea was represented in posterior and superior portions,
      with increasing eccentricities represented more anteriorly. The magnification of
      the fovea relative to the periphery was similar to that described for human
      primary visual cortex. The magnocellular regions of the LGN were distinguished
      based on their sensitivity to low stimulus contrast and tended to be located in
      its inferior and medial portions. Our results demonstrate striking similarities
      in the topographic organization of the macaque and human LGN and support accounts
      of a constant magnification from the retina through the cortex in both species.

PMID- 15483117
TI  - A mosaic of functional kainate receptors in hippocampal interneurons.
AB  - Although some physiological functions of kainate receptors (KARs) still remain
      unclear, recent advances have highlighted a role in synaptic physiology. In
      hippocampal slices, kainate depresses GABA-mediated synaptic inhibition and
      increases the firing rate of interneurons. However, the sensitivity to agonists
      of these responses differs, suggesting that the presynaptic and somatic KARs have
      a distinct molecular composition. Hippocampal interneurons express several
      distinct KAR subunits that can assemble into heteromeric receptors with a variety
      of pharmacological properties and that, in principle, could fulfill different
      roles. To address which receptor types mediate each of the effects of kainate in
      interneurons, we used new compounds and mice deficient for specific KAR subunits.
      In a recombinant assay, 5-carboxyl-2,4-di-benzamido-benzoic acid (NS3763) acted
      exclusively on homomeric glutamate receptor subunit 5 (GluR5), whereas
      3S,4aR,6S,8aR-6-((4-carboxyphenyl)methyl) 1,2,3,4,4a,5,6,7,8,8a
      decahydroisoquinoline-3-carboxylic acid (LY382884) antagonized homomeric GluR5
      and any heteromeric combination containing GluR5 subunits. In hippocampal slices,
      LY382884, but not NS3763, was able to prevent kainate-induced depression of
      evoked IPSC. In contrast, neither prevented the concomitant increase in
      spontaneous IPSC frequency. The selectivity of these compounds was seen
      additionally in knock-out mice, such that they were inactive in GluR5-/- mice but
      completely effective in GluR6-/- mice. Our data indicate that in wild-type mice,
      CA1 interneurons express heteromeric GluR6 -KA2 receptors in their somatic
      compartments and GluR5-GluR6 or GluR5-KA2 at presynaptic terminals. However,
      functional compensation appears to take place in the null mutants, a new
      pharmacological profile emerging more compatible with the activity of homomeric
      receptors in both compartments: GluR5 in GluR6-/- mice and GluR6 in GluR5-/-
      mice.

PMID- 15483118
TI  - Alpha2-chimaerin, cyclin-dependent Kinase 5/p35, and its target collapsin
      response mediator protein-2 are essential components in semaphorin 3A-induced
      growth-cone collapse.
AB  - Neurite outgrowth is influenced by positive and negative signals that include the
      semaphorins, an important family of axonal outgrowth inhibitors. Here we report
      that the Rac GTPase activating protein (GAP)alpha2-chimaerin is involved in
      Semaphorin 3A (Sema 3A) signaling. In dorsal root ganglion neurons, Sema 3A
      induced growth cone collapse was inhibited by alpha2-chimaerin mutated to
      eliminate GAP activity or interaction with phosphotyrosine. Activation of alpha2
      chimaerin by phorbol ester caused growth cone collapse. Active alpha2-chimaerin
      interacts with collapsin response mediator protein-2 (CRMP-2) and cyclin
      dependent kinase (Cdk) 5/p35 kinase through its SH2 and GAP domains,
      respectively. Cdk5 phosphorylates CRMP-2 at serine 522, possibly facilitating
      phosphorylation of serine 518 and threonine 514 by glycogen synthase kinase 3beta
      (GSK3beta), a kinase previously implicated in Sema 3A signaling. Phosphorylation
      of CRMP-2 serine 522 was essential for Sema 3A-induced growth cone collapse,
      which is dependent on Cdk5 but not Rho kinase activity. alpha2-chimaerin, like
      CRMP-2, can associate with the Sema 3A receptor. These results indicate that
      active alpha2-chimaerin Rac GAP, Cdk5/p35, and its substrate CRMP-2, are
      implicated in the dynamics of growth cone guidance initiated through Sema 3A
      signaling.

PMID- 15483119
TI  - Physiological and morphological characterization of dentate granule cells in the
      p35 knock-out mouse hippocampus: evidence for an epileptic circuit.
AB  - There is a high correlation between pediatric epilepsies and neuronal migration
      disorders. What remains unclear is whether there are intrinsic features of the
      individual dysplastic cells that give rise to heightened seizure susceptibility,
      or whether these dysplastic cells contribute to seizure activity by establishing
      abnormal circuits that alter the balance of inhibition and excitation. Mice
      lacking a functional p35 gene provide an ideal model in which to address these
      questions, because these knock-out animals not only exhibit aberrant neuronal
      migration but also demonstrate spontaneous seizures. Extracellular field
      recordings from hippocampal slices, characterizing the input-output relationship
      in the dentate, revealed little difference between wild-type and knock-out mice
      under both normal and elevated extracellular potassium conditions. However, in
      the presence of the GABA(A) antagonist bicuculline, p35 knock-out slices, but not
      wild-type slices, exhibited prolonged depolarizations in response to stimulation
      of the perforant path. There were no significant differences in the intrinsic
      properties of dentate granule cells (i.e., input resistance, time constant,
      action potential generation) from wild-type versus knock-out mice. However,
      antidromic activation (mossy fiber stimulation) evoked an excitatory synaptic
      response in over 65% of granule cells from p35 knock-out slices that was never
      observed in wild-type slices. Ultrastructural analyses identified morphological
      substrates for this aberrant excitation: recurrent axon collaterals, abnormal
      basal dendrites, and mossy fiber terminals forming synapses onto the spines of
      neighboring granule cells. These studies suggest that granule cells in p35 knock
      out mice contribute to seizure activity by forming an abnormal excitatory
      feedback circuit.

PMID- 15483120
TI  - Caenorhabditis elegans VEM-1, a novel membrane protein, regulates the guidance of
      ventral nerve cord-associated axons.
AB  - In the developing CNS, pathfinding growth cones use intermediate target- and
      pioneer axon-associated guidance cues to navigate along stereotypical
      trajectories. We previously showed that the novel membrane-associated protein
      Vema is localized to the floor plate and the optic chiasm, intermediate targets
      located at the ventral midline of the spinal cord and diencephalon in the
      developing rodent CNS, respectively. Here, we report that the Caenorhabditis
      elegans ortholog of vema, vem-1, is expressed by the AVG pioneer midline neuron
      and by several neurons that extend longitudinally projecting axons into the
      ventral nerve cord (VNC). In vem-1 mutants and vem-1 (RNAi) animals, a subset of
      posteriorly projecting interneuron axons either fail to extend ventrally to the
      VNC and, instead, assume aberrant lateral positions or are inappropriately
      located in the left tract of the VNC. In addition, ventral motor neuron axons
      exhibit pathfinding errors within the VNC and along the dorsoventral body axis.
      The conserved UNC-40/DCC and SAX-3-/Robo receptors mediate signaling events that
      regulate axon guidance in a wide variety of systems. Double-mutant analyses
      reveal that vem-1 genetically interacts with unc-40 and is likely to function in
      parallel with sax-3 to regulate the guidance of a subset of VNC-associated
      interneuron and motor neuron axons. Consistent with these genetic data, we also
      show that VEM-1 is capable of physically interacting with UNC-40 but not SAX-3.

PMID- 15483121
TI  - In vivo trafficking and targeting of N-cadherin to nascent presynaptic terminals.
AB  - N-cadherin is a prominent component of developing and mature synapses, yet very
      little is known about its trafficking within neurons. To investigate N-cadherin
      dynamics in developing axons, we used in vivo two-photon time-lapse microscopy of
      N-cadherin--green fluorescent protein (Ncad-GFP), which was expressed in Rohon
      Beard neurons of the embryonic zebrafish spinal cord. Ncad-GFP was present as
      either stable accumulations or highly mobile transport packets. The mobile
      transport packets were of two types: tubulovesicular structures that moved
      preferentially in the anterograde direction and discrete-punctate structures that
      exhibited bidirectional movement. Stable puncta of Ncad-GFP accumulated in the
      wake of the growth cone with a time course. Colocalization of Ncad-GFP puncta
      with synaptic markers suggests that N-cadherin is a very early component of
      nascent synapses. Expression of deletion mutants revealed a potential role of the
      extracellular domain in appropriate N-cadherin trafficking and targeting. These
      results are the first to characterize the trafficking of a synaptic cell-adhesion
      molecule in developing axons in vivo. In addition, we have begun to investigate
      the cell biology of N-cadherin trafficking and targeting in the context of an
      intact vertebrate embryo.

PMID- 15483122
TI  - A population decoding framework for motion aftereffects on smooth pursuit eye
      movements.
AB  - Both perceptual and motor systems must decode visual information from the
      distributed activity of large populations of cortical neurons. We have sought a
      common framework for understanding decoding strategies for visually guided
      movement and perception by asking whether the strong motion aftereffects seen in
      the perceptual domain lead to similar expressions in motor output. We found that
      motion adaptation indeed has strong sequelae in the direction and speed of smooth
      pursuit eye movements. After adaptation with a stimulus that moves in a given
      direction for 7 sec, the direction of pursuit is repelled from the direction of
      pursuit targets that move within 90 degrees of the adapting direction. The speed
      of pursuit decreases for targets that move at the direction and speed of the
      adapting stimulus and is repelled from the adapting speed in the sense that the
      decrease either becomes greater or smaller (eventually turning to an increase)
      when tracking targets move slower or faster than the adapting speed. The effects
      of adaptation are spatially specific and fixed to the retinal location of the
      adapting stimulus. The magnitude of adaptation of pursuit speed and direction is
      uncorrelated, suggesting that the two parameters are decoded independently.
      Computer simulation of motion adaptation in the middle temporal visual area (MT)
      shows that vector-averaging decoding of the population response in MT can account
      for the effects of adaptation on the direction of pursuit. Our results suggest a
      unified framework for thinking, in terms of population decoding, about motion
      adaptation for both perception and action.

PMID- 15483123
TI  - Requirement for the RIIbeta isoform of PKA, but not calcium-stimulated adenylyl
      cyclase, in visual cortical plasticity.
AB  - The cAMP-dependent protein kinase (PKA) signaling pathway plays a key role in
      visual cortical plasticity. Inhibitors that block activation of all PKA
      regulatory subunits (RIalpha,RIbeta, RIIalpha, RIIbeta) abolish long-term
      potentiation (LTP) and long-term depression (LTD) in vitro and ocular dominance
      plasticity (ODP) in vivo. The details of this signaling cascade, however,
      including the source of PKA signals and which PKA subunits are involved, are
      unknown. To investigate these issues we have examined LTP, LTD, and ODP in knock
      out mice lacking either the two cortically expressed Ca2+-stimulated adenylyl
      cyclases (AC1 and AC8) or the predominant neocortical subunit of PKA (RIIbeta).
      Here we show that plasticity remains intact in AC1/AC8-/- mice, whereas ODP and
      LTD, but not LTP, are absent in RIIbeta-/- mice. We conclude that (1) plasticity
      in the visual cortex does not require the activity of known Ca2+-stimulated
      adenylyl cyclases, (2) the PKA dependence of ODP and LTD, but not LTP, is
      mediated by RIIbeta-PKA, and (3) multiple isoforms of PKA contribute to LTD.

PMID- 15483124
TI  - Two interdependent TRPV channel subunits, inactive and Nanchung, mediate hearing
      in Drosophila.
AB  - Hearing in Drosophila depends on the transduction of antennal vibration into
      receptor potentials by ciliated sensory neurons in Johnston's organ, the antennal
      chordotonal organ. We previously found that a Drosophila protein in the vanilloid
      receptor subfamily (TRPV) channel subunit, Nanchung (NAN), is localized to the
      chordotonal cilia and required to generate sound-evoked potentials (Kim et al.,
      2003). Here, we show that the only other Drosophila TRPV protein is mutated in
      the behavioral mutant inactive (iav). The IAV protein forms a hypotonically
      activated channel when expressed in cultured cells; in flies, it is specifically
      expressed in the chordotonal neurons, localized to their cilia and required for
      hearing. IAV and NAN are each undetectable in cilia of mutants lacking the other
      protein, indicating that they both contribute to a heteromultimeric transduction
      channel in vivo. A functional green fluorescence protein-IAV fusion protein shows
      that the channel is restricted to the proximal cilium, constraining models for
      channel activation.

PMID- 15483125
TI  - Phase sensitivity of synaptic modifications in oscillating cells of rat visual
      cortex.
AB  - Synaptic modifications depend on the amplitude and temporal relations of
      presynaptic and postsynaptic activation. The interactions among these variables
      are complex and hard to predict when neurons engage in synchronized high
      frequency oscillations in the beta and gamma frequency range, as is often
      observed during signal processing in the cerebral cortex. Here we investigate in
      layer II/III pyramidal cells of rat visual cortex slices how synapses change when
      synchronized, oscillatory multifiber activity impinges on postsynaptic neurons
      during membrane potential (V(m)) oscillations at 20 and 40 Hz. Synapses underwent
      long-term potentiation (LTP) when EPSPs coincided with the peaks of the V(m)
      oscillations but exhibited long-term depression (LTD) when EPSPs coincided with
      the troughs. The induction of LTP but not of LTD was NMDA receptor dependent,
      required additional activation of muscarinic receptors in older animals, and
      persisted in a kainate-driven increased conductance state. Thus, even when
      neuronal networks engage in high-frequency oscillations, synaptic plasticity
      remains exquisitely sensitive to the timing of discharges. This is an essential
      prerequisite for theories which assume that precise synchronization of discharges
      serves as signature of relatedness in distributed processing.

PMID- 15483126
TI  - Optical postsynaptic measurement of vesicle release rates for hippocampal
      synapses undergoing asynchronous release during train stimulation.
AB  - Developing hippocampal neurons in microisland culture were found to undergo rapid
      depression of excitatory synaptic activity caused by consumption of their readily
      releasable pool (RRP) of vesicles in response to 20 Hz trains of stimulation.
      Associated with depression was a switch to an asynchronous release mode that
      maintained transmission at a high steady-state rate equivalent to approximately
      2.1 RRPs per second. We have applied postsynaptic Ca2+ imaging to directly
      monitor these asynchronous release events to estimate both the steady rate of
      transmitter release and the number of quanta within the RRP at individual
      hippocampal synapses. Based on the frequency of asynchronous release measured at
      individual synapses postsynaptically using Ca2+ imaging (5-17 sec after train
      stimulation) and with knowledge of the time course by which asynchronous release
      rates decay, we estimate that individual hippocampal synapses exhibit (in
      response to train stimulation) peak release rates of up to 21 quanta per second
      from an RRP that contains, on average, 10 quanta. Use-dependent block of evoked
      synaptic activity by MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo
      [a,d]cyclohepten-5,10-imine maleate] confirmed that synapses undergoing
      asynchronous release are not significantly different from the general population
      with regard to their composition of NMDA receptor and/or release probability.
      Given that high-frequency trains deplete the synapse of readily releasable quanta
      (and that these release rates can only be maintained for a few seconds), these
      high rates of asynchronous release likely reflect refilling of vesicles from a
      reserve pool and not necessarily the continuous action of a relatively slow
      clathrin- and endosome-dependent process.

PMID- 15483127
TI  - Differential requirements for semaphorin 3F and Slit-1 in axonal targeting,
      fasciculation, and segregation of olfactory sensory neuron projections.
AB  - The formation of precise stereotypic connections in sensory systems is critical
      for defining accurate internal representations of the external world; however,
      the molecular mechanisms underlying the formation of sensory maps are poorly
      understood. Here, we examine the roles of two structurally unrelated repulsive
      guidance cues, semaphorin 3F (Sema3F) and Slit-1, in olfactory sensory axon
      fasciculation, targeting, and segregation. Using sema3F-/- mice, we show that
      Sema3F is critical for vomeronasal sensory neuron axonal fasciculation and for
      segregation of these sensory afferents from the main olfactory system; however,
      Sema3F plays only a minor role in targeting of apical vomeronasal neuron axons to
      the anterior accessory olfactory bulb (AOB). In addition, we show that Sema3F is
      required for lamina-specific targeting of olfactory sensory axons within the main
      olfactory system. In contrast to Sema3F, Slit-1 is dispensable for fasciculation
      of basal vomeronasal neuron axons but is critical for targeting these axons to
      the posterior AOB. These results reveal discrete and complementary roles for
      secreted semaphorins and slits in axonal targeting, fasciculation, and
      segregation of olfactory sensory neuron projections.

PMID- 15483128
TI  - Tyrosine residues that control binding and gating in the 5-hydroxytryptamine3
      receptor revealed by unnatural amino acid mutagenesis.
AB  - The mechanism by which agonist binding triggers pore opening in ligand-gated ion
      channels is poorly understood. Here, we used unnatural amino acid mutagenesis to
      introduce subtle changes to the side chains of tyrosine residues (Tyr141, Tyr143,
      Tyr153, and Tyr234), which dominate the 5-HT3 receptor binding site. Heterologous
      expression in oocytes, combined with radioligand binding data and a model of 5-HT
      (serotonin) computationally docked into the binding site, has allowed us to
      determine which of these residues are responsible for binding and/or gating. We
      have shown that Tyr 143 forms a hydrogen bond that is essential for receptor
      gating but does not affect binding, whereas a hydrogen bond formed by Tyr153 is
      involved in both binding and gating of the receptor. The aromatic group of Tyr234
      is essential for binding and gating, whereas its hydroxyl does not affect binding
      but plays a steric role in receptor gating. Tyr141 is not involved in agonist
      binding or receptor gating but is important for antagonist interactions. These
      data, combined with a new model of the nonliganded 5-HT3 receptor, lead to a
      mechanistic explanation of the interactions that initiate the conformational
      change leading to channel opening. Thus, we suggest that agonist entry into the
      binding pocket may displace Tyr143 and Tyr153 and results in their forming new
      hydrogen bonds. These bonds may form part of the network of bond rearrangements
      that trigger the conformational change leading to channel opening. Similar
      rearrangements may initiate gating in all Cys-loop receptors.

PMID- 15483129
TI  - The Drosophila metabotropic glutamate receptor DmGluRA regulates activity
      dependent synaptic facilitation and fine synaptic morphology.
AB  - In vertebrates, several groups of metabotropic glutamate receptors (mGluRs) are
      known to modulate synaptic properties. In contrast, the Drosophila genome encodes
      a single functional mGluR (DmGluRA), an ortholog of vertebrate group II mGluRs,
      greatly expediting the functional characterization of mGluR-mediated signaling in
      the nervous system. We show here that DmGluRA is expressed at the glutamatergic
      neuromuscular junction (NMJ), localized in periactive zones of presynaptic
      boutons but excluded from active sites. Null DmGluRA mutants are completely
      viable, and all of the basal NMJ synaptic transmission properties are normal. In
      contrast, DmGluRA mutants display approximately a threefold increase in synaptic
      facilitation during short stimulus trains. Prolonged stimulus trains result in
      very strongly increased ( approximately 10-fold) augmentation, including the
      appearance of asynchronous, bursting excitatory currents never observed in wild
      type. Both defects are rescued by expression of DmGluRA only in the neurons,
      indicating a specific presynaptic requirement. These phenotypes are reminiscent
      of hyperexcitable mutants, suggesting a role of DmGluRA signaling in the
      regulation of presynaptic excitability properties. The mutant phenotypes could
      not be replicated by acute application of mGluR antagonists, suggesting that
      DmGluRA regulates the development of presynaptic properties rather than directly
      controlling short-term modulation. DmGluRA mutants also display mild defects in
      NMJ architecture: a decreased number of synaptic boutons accompanied by an
      increase in mean bouton size. These morphological changes bidirectionally
      correlate with DmGluRA levels in the presynaptic terminal. These data reveal the
      following two roles for DmGluRA in presynaptic mechanisms: (1) modulation of
      presynaptic excitability properties important for the control of activity
      dependent neurotransmitter release and (2) modulation of synaptic architecture.

PMID- 15483131
TI  - Spike timing of distinct types of GABAergic interneuron during hippocampal gamma
      oscillations in vitro.
AB  - Gamma frequency (30-100 Hz) network oscillations occur in the intact hippocampus
      during awake, attentive behavior. Here, we explored the underlying cellular
      mechanisms in an in vitro model of persistent gamma-frequency oscillations,
      induced by bath application of 20 microm carbachol in submerged hippocampal
      slices at 30 +/- 1 degrees C. Current-source density analysis of the field
      oscillation revealed a prominent alternating sink-source pair in the perisomatic
      and apical dendritic regions of CA3. To elucidate the active events generating
      these extracellular dipoles, we examined the firing properties of distinct neuron
      types. Visually guided unit recordings were obtained from individual CA3 neurons
      followed by intracellular labeling for anatomical identification. Pyramidal cells
      fired at 2.82 +/- 0.7 Hz, close to the negative peak of the oscillation (0.03 +/-
      0.65 msec), and often in conjunction with a negative spike-like component of the
      field potential. In contrast, all phase-coupled interneurons fired after this
      negative peak. Perisomatic inhibitory interneurons fired at high frequency (18.1
      +/- 2.7 Hz), shortly after the negative peak (1.97 +/- 0.95 msec) and were
      strongly phase-coupled. Dendritic inhibitory interneurons fired at lower
      frequency (8.4 +/- 2.4 Hz) and with less fidelity and a longer delay after the
      negative peak (4.3 +/- 1.1 msec), whereas interneurons with cell body in the
      stratum radiatum often showed no phase relationship with the field oscillation.
      The phase and spike time data of individual neurons, together with the current
      source density analysis, support a synaptic feedback model of gamma oscillations
      primarily involving pyramidal cells and inhibitory cells targeting their
      perisomatic region.

PMID- 15483130
TI  - A mouse model of classical late-infantile neuronal ceroid lipofuscinosis based on
      targeted disruption of the CLN2 gene results in a loss of tripeptidyl-peptidase I
      activity and progressive neurodegeneration.
AB  - Mutations in the CLN2 gene, which encodes a lysosomal serine protease,
      tripeptidyl-peptidase I (TPP I), result in an autosomal recessive
      neurodegenerative disease of children, classical late-infantile neuronal ceroid
      lipofuscinosis (cLINCL). cLINCL is inevitably fatal, and there currently exists
      no cure or effective treatment. In this report, we provide the characterization
      of the first CLN2-targeted mouse model for cLINCL. CLN2-targeted mice were
      fertile and apparently healthy at birth despite an absence of detectable TPP I
      activity. At approximately 7 weeks of age, neurological deficiencies became
      evident with the onset of a tremor that became progressively more severe and was
      eventually accompanied by ataxia. Lifespan of the affected mice was greatly
      reduced (median survival, 138 d), and extensive neuronal pathology was observed
      including a prominent accumulation of cytoplasmic storage material within the
      lysosomal-endosomal compartment, a loss of cerebellar Purkinje cells, and
      widespread axonal degeneration. The CLN2-targeted mouse therefore recapitulates
      much of the pathology and clinical features of cLINCL and represents an animal
      model that should provide clues to the normal cellular function of TPP I and the
      pathogenic processes that underlie neuronal death in its absence. In addition,
      the CLN2-targeted mouse also represents a valuable model for the evaluation of
      different therapeutic strategies.

PMID- 15483132
TI  - Role of cerebellar interpositus nucleus in the genesis and control of reflex and
      conditioned eyelid responses.
AB  - The role of cerebellar circuits in the acquisition of new motor abilities is
      still a matter of intensive debate. To establish the contribution of posterior
      interpositus nucleus (PIN) to the performance and/or acquisition of reflex and
      classically conditioned responses (CRs) of the eyelid, the effects of
      microstimulation and/or pharmacological inhibition by muscimol of the nucleus
      were investigated in conscious cats. Microstimulation of the PIN in naive animals
      evoked ramp-like eyelid responses with a wavy appearance, without producing any
      noticeable plastic functional change in the cerebellar and brainstem circuits
      involved. Muscimol microinjections decreased the amplitude of reflex eyeblinks
      evoked by air puffs, both when presented alone or when paired with a tone as
      conditioned stimulus (CS). In half-conditioned animals, muscimol injections also
      decreased the amplitude and damped the typical wavy profile of CRs, whereas
      microstimulation of the same sites increased both parameters. However, neither
      muscimol injections nor microstimulation modified the expected percentage of CRs,
      suggesting a major role of the PIN in the performance of eyelid responses rather
      than in the learning process. Moreover, the simultaneous presentation of CS and
      microstimulation in well trained animals evoked CRs similar in amplitude to the
      added value of those evoked by the two stimuli presented separately. In contrast,
      muscimol-injected animals developed CRs to paired CS and microstimulation
      presentations, larger than those evoked by the two stimuli when presented alone.
      It is concluded that the PIN contributes to the enhancement of both reflex and
      conditioned eyelid responses and to the damping of resonant properties of
      neuromuscular elements controlling eyelid kinematics.

PMID- 15483133
TI  - Three mechanisms underlie KCNQ2/3 heteromeric potassium M-channel potentiation.
AB  - The non-inactivating potassium M-current exerts a strong influence on neuronal
      excitability. The channels responsible for this current are made up of KCNQ
      subunits, and mutations in most of these produce human pathologies. Notably, in
      terms of excitation, mutations in either KCNQ2 or KCNQ3 lead to benign neonatal
      familial convulsions. Although a mere reduction of 25% in KCNQ2/3 function can
      increase excitability to epileptogenic levels, the potentiation of these subunits
      has anti-epileptogenic effects. After KCNQ2/3 heteromerization, current levels
      can augment as much as 10-fold, and we have discovered that there are three
      processes underlying this potentiation. First, there is an increase in the number
      of channels inserted in the membrane after heteromerization of the C-terminal
      region. Second, the N-terminal domain from KCNQ2 exerts a negative influence on
      the current level. Finally, Ala 315 of KCNQ3, a residue located in the inner
      vestibule after the selectivity filter, plays a critical role in preventing
      current flow in KCNQ3 homomeric channels, whereas it is permissive in heteromers
      in combination with Thr at the equivalent 276 position of KCNQ2.

PMID- 15483134
TI  - The role of the insular cortex in pitch pattern perception: the effect of
      linguistic contexts.
AB  - Auditory pitch patterns are significant ecological features to which nervous
      systems have exquisitely adapted. Pitch patterns are found embedded in many
      contexts, enabling different information-processing goals. Do the psychological
      functions of pitch patterns determine the neural mechanisms supporting their
      perception, or do all pitch patterns, regardless of function, engage the same
      mechanisms? This issue is pursued in the present study by using 150-water
      positron emission tomography to study brain activations when two subject groups
      discriminate pitch patterns in their respective native languages, one of which is
      a tonal language and the other of which is not. In a tonal language, pitch
      patterns signal lexical meaning. Native Mandarin-speaking and English-speaking
      listeners discriminated pitch patterns embedded in Mandarin and English words and
      also passively listened to the same stimuli. When Mandarin listeners
      discriminated pitch embedded in Mandarin lexical tones, the left anterior insular
      cortex was the most active. When they discriminated pitch patterns embedded in
      English words, the homologous area in the right hemisphere activated as it did in
      English-speaking listeners discriminating pitch patterns embedded in either
      Mandarin or English words. These results support the view that neural responses
      to physical acoustic stimuli depend on the function of those stimuli and
      implicate anterior insular cortex in auditory processing, with the left insular
      cortex especially responsive to linguistic stimuli.

PMID- 15483135
TI  - Group I metabotropic glutamate receptor NMDA receptor coupling and signaling
      cascade mediate spinal dorsal horn NMDA receptor 2B tyrosine phosphorylation
      associated with inflammatory hyperalgesia.
AB  - Hindpaw inflammation induces tyrosine phosphorylation (tyr-P) of the NMDA
      receptor (NMDAR) 2B (NR2B) subunit in the rat spinal dorsal horn that is closely
      related to the initiation and development of hyperalgesia. Here, we show that in
      rats with Freund's adjuvant-induced inflammation, the increased dorsal horn NR2B
      tyr-P is blocked by group I metabotropic glutamate receptor (mGluR) antagonists
      [7-(hydroxyimino)cyclopropa[b] chromen-1a-carboxylate ethyl ester (CPCCOEt) and 2
      methyl-6-(phenylethynyl)-pyridine (MPEP), by the Src inhibitor CGP 77675, but not
      by the MAP kinase inhibitor 2'-amino-3'-methoxyflavone. Analysis of the calcium
      pathways shows that the in vivo NR2B tyr-P is blocked by an IP3 receptor
      antagonist 2-aminoethoxydiphenylborate (2APB) but not by antagonists of
      ionotropic glutamate receptors and voltage-dependent calcium channels, suggesting
      that the NR2B tyr-P is dependent on intracellular calcium release. In a dorsal
      horn slice preparation, the group I (dihydroxyphenylglycine), but not group II
      [(2R,4R)-4-aminopyrrolidine-2,3-dicarboxylate] and III [L-AP 4 (L-(+)-2-amino-4
      phosphonobutyric acid)], mGluR agonists, an IP3 receptor (D-IP3) agonist, and a
      PKC (PMA) activator, induces NR2B tyr-P similar to that seen in vivo after
      inflammation. Coimmunoprecipitation indicates that Shank, a postsynaptic density
      protein associated with mGluRs, formed a complex involving PSD-95 (postsynaptic
      density-95), NR2B, and Src in the spinal dorsal horn. Double immunofluorescence
      studies indicated that NR1 is colocalized with mGluR5 in dorsal horn neurons.
      mGluR5 also coimmunoprecipitates with NR2B. Finally, intrathecal pretreatment of
      CPCCOEt, MPEP, and 2APB attenuates inflammatory hyperalgesia. Thus, inflammation
      and mGluR-induced NR2B tyr-P share similar mechanisms. The group ImGluR-NMDAR
      coupling cascade leads to phosphorylation of the NMDAR and appears necessary for
      the initiation of spinal dorsal horn sensitization and behavioral hyperalgesia
      after inflammation.

PMID- 15483136
TI  - Evidence that DeltaNp73 promotes neuronal survival by p53-dependent and p53
      independent mechanisms.
AB  - The p53 family member, p73, is essential for the survival of sympathetic neurons
      during the developmental period of naturally occurring neuronal death. Here, we
      have asked whether DeltaNp73, which is the only p73 isoform expressed in
      sympathetic neurons, mediates this survival by p53-dependent and/or p53
      independent mechanisms. Initially, we used a genetic approach and crossed p53+/-
      and p73+/- mice. Quantitation of neurons in the sympathetic superior cervical
      ganglion during the period of naturally occurring cell death revealed that the
      loss of p53 partially rescued the death of neurons seen in p73-/- animals.
      Moreover, exogenous expression of DeltaNp73 in cultured p53-/- sympathetic
      neurons rescued these neurons from apoptosis after NGF withdrawal. Biochemical
      studies asking how DeltaNp73 inhibited NGF withdrawal-induced apoptosis in wild
      type neurons demonstrated that it prevented the upregulation of the direct p53
      targets p21 and Apaf-1 as well as cleavage of caspase-3. It also inhibited events
      at the mitochondrial apoptotic checkpoint, suppressing the induction of BimEL and
      the release of mitochondrial cytochrome c. Interestingly, DeltaNp73 expression
      also inhibited one very early event in the apoptotic cascade, the activation of c
      Jun N-terminal protein kinase (JNK), likely by binding directly to JNK. Finally,
      we show that neuronal cell size is decreased in p73-/- mice, and that this
      decrease is not rescued by the lack of p53, suggesting a role for p73 in
      regulating cell size that does not involve interactions with p53. Thus, DeltaNp73
      promotes neuronal survival via p53-dependent and -independent mechanisms, and it
      does so at multiple points, including some of the most proximal events that occur
      after NGF withdrawal.

PMID- 15483137
TI  - The integration of multiple stimulus features by V1 neurons.
AB  - We investigated how V1 neurons integrate two stimulus features by presenting
      stimuli from a stimulus set made up of all combinations of eight different
      directions of motion and nine binocular disparities. We investigated the
      occurrence and shape of the resulting joint tuning function. Among V1 neurons,
      approximately 80% were jointly tuned for disparity with orientation or direction.
      The joint tuning function of all jointly tuned neurons was separable into
      distinct tuning for disparity on the one hand, and orientation or direction
      tuning on the other. The degree of separability and the mutual information
      between the stimulus and the firing rates were strongly correlated. The mutual
      information of jointly tuned neurons when both features were decoded together was
      highly correlated with the mutual information when the two features were decoded
      separately, and the information was then summed. Jointly tuned neurons were just
      as good at representing information about single features as neurons tuned for
      only a single feature. The tuning properties of most jointly tuned neurons did
      not dynamically evolve over time, nor did jointly tuned neurons respond earlier
      than neurons tuned for only a single feature. The response selectivity of V1
      neurons is low and decreases the information that a neuron represents about a
      stimulus. Together these results suggest that distinct stimulus features are
      integrated very early in visual processing. Furthermore, V1 generates a
      distributed representation through low response selectivity that avoids the curse
      of dimensionality by using separable joint tuning functions.

PMID- 15483138
TI  - Olfaction in olfactory bulbectomized rats.
AB  - Experimental rats had their right olfactory bulb removed on postnatal day 2 (P2)
      and their left olfactory bulb removed on P90. Control rats had one or both
      olfactory bulbs removed on P90. Before and after their adult-stage surgery, rats
      were trained using olfactometry and operant conditioning to detect and
      discriminate odors. Anterograde transport of horseradish peroxidase applied to
      the olfactory epithelium revealed numerous axons of olfactory sensory neurons in
      the right hemisphere of 27 experimental rats. These axons terminated in
      glomerular-like clusters within the frontal neocortex (n = 5) or anterior
      olfactory nucleus with some axons extending into the subventricular epithelium (n
      = 22). Seventeen of the experimental rats were able to detect a variety of odors
      and to discriminate between odors. Performance accuracy was related to the
      location and density of these anomalous inputs; experimental rats with inputs
      confined to frontal neocortex and those lacking any inputs to the forebrain were
      anosmic, as were adult-operated bilaterally bulbectomized rats. Our results
      provide strong support for the contention that, in the absence of the olfactory
      bulbs, olfactory connections to novel forebrain sites can support both odor
      detection and odor discrimination.

PMID- 15483139
TI  - Modulation power and phase spectrum of natural sounds enhance neural encoding
      performed by single auditory neurons.
AB  - We examined the neural encoding of synthetic and natural sounds by single neurons
      in the auditory system of male zebra finches by estimating the mutual information
      in the time-varying mean firing rate of the neuronal response. Using a novel
      parametric method for estimating mutual information with limited data, we tested
      the hypothesis that song and song-like synthetic sounds would be preferentially
      encoded relative to other complex, but non-song-like synthetic sounds. To test
      this hypothesis, we designed two synthetic stimuli: synthetic songs that matched
      the power of spectral-temporal modulations but lacked the modulation phase
      structure of zebra finch song and noise with uniform band-limited spectral
      temporal modulations. By defining neural selectivity as relative mutual
      information, we found that the auditory system of songbirds showed selectivity
      for song-like sounds. This selectivity increased in a hierarchical manner along
      ascending processing stages in the auditory system. Midbrain neurons responded
      with highest information rates and efficiency to synthetic songs and thus were
      selective for the spectral-temporal modulations of song. Primary forebrain
      neurons showed increased information to zebra finch song and synthetic song
      equally over noise stimuli. Secondary forebrain neurons responded with the
      highest information to zebra finch song relative to other stimuli and thus were
      selective for its specific modulation phase relationships. We also assessed the
      relative contribution of three response properties to this selectivity: (1)
      spiking reliability, (2) rate distribution entropy, and (3) bandwidth. We found
      that rate distribution and bandwidth but not reliability were responsible for the
      higher average information rates found for song-like sounds.

PMID- 15483140
TI  - Invited review: guidelines for measuring and reporting calf and heifer
      experimental data.
AB  - Based on a 5-yr review of published reports, reporting of materials, methods, and
      data for calf and heifer studies is often not very complete. The number of calves
      or heifers per treatment was often inadequate to detect meaningful and
      statistically significant differences with observed variability. A set of
      guidelines is provided to assist in designing and planning experiments,
      collection of data, and summation and reporting. The guidelines may also be
      useful to reviewers as a checkpoint of information needed or desired.

PMID- 15483141
TI  - Impact of milk preacidification with CO2 on cheddar cheese composition and yield.
AB  - Preacidification of milk for cheese making may have a beneficial impact on
      increasing proteolysis during cheese aging. Unlike other acids, CO(2) can easily
      be removed from whey. The objectives of this work were to determine the effect of
      milk preacidification on Cheddar cheese composition, the recovery of individual
      milk components, and yield. Carbon dioxide was injected inline after the cooling
      section of the pasteurizer. Cheeses with and without added CO(2) were made
      simultaneously from the same batch of milk. This procedure was replicated 3
      times. Carbon dioxide in the cheese milk was about 1600 ppm, which resulted in a
      milk pH of about 5.9 at 31 degrees C. The starter culture and coagulant addition
      rates were the same for both the CO(2) treatment and the control. The whey pH at
      draining of the CO(2) treatment was lower than the control. Total make time was
      shorter for the CO(2) treatment compared with the control. Cheese manufactured
      from milk acidified with CO(2) retained less of the total calcium and fat than
      the control cheese. The higher fat loss was primarily in the whey at draining.
      Preacidification with CO(2) did not alter the crude protein recovery in the
      cheese. The CO(2) treatment resulted in a higher added salt recovery in the
      cheese and produced a cheese that contained too much salt. Considering the higher
      added salt retention, the salt application rate could be lowered to achieve a
      typical cheese salt content. Cheese yield efficiency of the CO(2) treated milk
      was 4.4% lower than the control due to fat loss. Future work will focus on
      modifying the make procedure to achieve a normal fat loss into the whey when
      CO(2) is added to milk.

PMID- 15483142
TI  - Impact of milk preacidification with CO2 on the aging and proteolysis of cheddar
      cheese.
AB  - To determine the influence of milk preacidification with CO(2) on Cheddar cheese
      aging and proteolysis, cheese was manufactured from milk with and without added
      CO(2). The experiment was replicated 3 times. Carbon dioxide (approximately 1600
      ppm) was added to the cold milk, resulting in a milk pH of 5.9 at 31 degrees C in
      the cheese vat. The starter and coagulant usage rates were equal for the control
      and CO(2) treatment cheeses. The calcium content of the CO(2) treatment cheese
      was lower, but no difference in moisture content was detected. The higher CO(2)
      content of the treatment cheeses (337 vs. 124 ppm) was maintained throughout 6 mo
      of aging. In spite of having almost one and a half times the salt-in-moisture,
      proteolysis as measured by pH 4.6 and 12% trichloroacetic acid soluble nitrogen
      expressed as percentages of total nitrogen, was higher in the CO(2) treatment
      cheeses throughout aging. The ratio of alpha(s)-casein (CN) to para-kappa-CN
      decreased faster in the CO(2) treatment cheeses than in the control cheeses,
      especially before refrigerated storage. No difference was detected in the ratio
      of beta-CN to para-kappa-CN between the control and CO(2) treatment cheeses.
      Intact alpha(s)- and beta-CN were found in the expressible serum (ES) from the
      CO(2) treatment cheese as well as alpha(s1)-I-CN, but they were not detected in
      the ES from the control cheese. No CN was detected in the ES from the curd before
      the salting of either the control or CO(2) treatment cheese. Higher proteolysis
      in the cheese made from milk preacidified with CO(2) may have been due to
      increased substrate availability in the water phase or increased chymosin
      activity or retention in the cheese.

PMID- 15483143
TI  - Vatless manufacturing of low-moisture part-skim mozzarella cheese from highly
      concentrated skim milk microfiltration retentates.
AB  - Low-moisture, part-skim (LMPS) Mozzarella cheeses were made from concentration
      factor (CF) 6, 7, 8, and 9, pH 6.0 skim milk microfiltration (MF) retentates
      using a vatless cheese-making process. The compositional and proteolytic effects
      of cheese made from 4 CF retentates were evaluated as well as their functional
      properties (meltability and stretchability). Pasteurized skim milk was
      microfiltered using a 0.1-microm ceramic membrane at 50 degrees C to a retentate
      CF of 6, 7, 8, and 9. An appropriate amount of cream was added to achieve a
      constant casein:fat ratio in the 4 cheesemilks. The ratio of rennet to casein was
      also kept constant in the 4 cheesemilks. The compositional characteristics of the
      cheeses made from MF retentates did not vary with retentate CF and were within
      the legal range for LMPS Mozzarella cheese. The observed reduction in whey
      drained was greater than 90% in the cheese making from the 4 CF retentates
      studied. The development of proteolytic and functional characteristics was slower
      in the MF cheeses than in the commercial samples that were used for comparison
      due to the absence of starter culture, the lower level of rennet used, and the
      inhibition of cheese proteolysis due to the inhibitory effect of residual whey
      proteins retained in the MF retentates, particularly high molecular weight
      fractions.

PMID- 15483144
TI  - Isolation and characterization of copolymers of beta-lactoglobulin, alpha
      lactalbumin, kappa-casein, and alphas1-casein generated by pressurization and
      thermal treatment of raw milk.
AB  - Raw skim milk was submitted to high pressure (300 to 600 MPa) and temperature (4
      to 70 degrees C) treatments for 2 or 5 min. The combined effects of pressure and
      temperature on milk proteins induced structural changes and polymer and copolymer
      formation characterized by anion-exchange and size-exclusion fast protein liquid
      chromatography and electrophoretic techniques. Approximately half of the beta
      lactoglobulin formed polymers, and the other half formed large copolymers, mainly
      with kappa-casein, alpha-lactalbumin via intermolecular disulfide bond exchange,
      and alpha(s1)-casein via physicochemical interactions, in proportions of
      1.0:0.7:0.3:0.1, respectively. Minor whey proteins (serum albumin,
      immunoglobulins, and lactoferrin) also participated in the formation of the
      copolymers but to a lesser extent. Two populations of the copolymers were found
      with apparent molecular masses ranging from 440 to 2000 kDa for the first and
      more than 2000 kDa for the second. On the contrary, for heated milks the
      aggregation kinetics obtained by combination of high pressure and thermal
      treatment were very fast, as no intermediates such as dimers and small size
      oligomers were observed after pressurization, whatever the temperature studied.
      Lactosylation of proteins as well as proteolysis were very limited. A beta-casein
      amino-terminal peptide of 22 kDa was specifically recovered in milk samples
      treated under the more drastic conditions (500 MPa/55 degrees C per 5 min and 600
      MPa/70 degrees C per 5 min) and might have been generated by neutral proteases
      such as elastase released from somatic cells present in milk. No casein was
      released from the micelle whatever the combination of high pressure and
      temperature studied.

PMID- 15483145
TI  - Evaluation of rapid somatic cell counters under different analytical conditions
      in ovine milk.
AB  - A total of 31 individual ovine milk samples, ranging between 30 and 2600 x 10(3)
      cells/mL, were divided into 8 aliquots/milk with the objective of studying the
      overall accuracy of 2 rapid somatic cell count (SCC) counters, one based on
      cytometry on disk (Fossomatic 360) and the other on flow cytometry (Fossomatic
      5000), under 4 types of preservation (without preservation, bronopol, sodium
      azide, and potassium dichromate) and 2 analytical temperatures (40 and 60 degrees
      C). All analyses were carried out in duplicate. In addition, each sample was
      analyzed in quadruplicate by reference microscopic method using Pyronin Y-methyl
      green as a stain. A second experiment using 13 samples divided into 20 aliquots/
      sample, enabled repeatability to be studied depending on the values obtained in
      the SCC and on the SCC equipment used. Comparison of the methods was based on
      repeatability and accuracy studies (means comparison and regression studies vs.
      reference method). Both counters gave adequate repeatability and accuracy values
      in ovine milk, though the SCC obtained by Fossomatic 5000 was closer to the
      reference method and was somewhat more repeatable than Fossomatic 360. In the
      regression study, slope and intercept values were statistically different from
      their theoretical values (1.00 and 0.00, respectively) in the unpreserved samples
      but not in the preserved ones. In all cases, correlation coefficients very close
      to 1.00 were obtained. The preserved milk analyzed by flow cytometry gave optimal
      repeatability values (s(r) = 16.3 to 19.7 and s(r)% = 1.9 to 2.4), and their
      logSCC means (5.62 to 5.64) were not different from the reference value (5.63).
      Bronopol was the optimal preservative for the Fossomatic method. Analytical
      temperature did not contribute significantly to SCC variation, although disk
      cytometry gave slightly more repeatable SCC at 40 degrees than at 60 degrees C.

PMID- 15483147
TI  - A study of beta-casein tertiary structure by intramolecular crosslinking and mass
      spectrometry.
AB  - The objective of this study was to obtain experimental evidence to extend the
      discussion on the 3-D structure of beta-casein (beta-CN). The approach involved
      the preparation of homobifunctional crosslinkers, bis(sulfosuccinimidyl)
      derivatives of dicarboxylic acids of several lengths, which specifically react
      with primary amines of lysinyl residues or the N-terminal in the protein. The
      intramolecular crosslinks formed were determined by enzymatic digestion and by
      matrix-assisted laser desorption and ionization time-of-flight mass spectrometry
      combined with comparison against the theoretical digestion patterns. This
      procedure allowed the measurement of distances between the crosslinked residues.
      Ten different masses arising from 8 different specific intramolecular crosslinks
      were identified. Of these, 5 crosslinks were in good agreement with a published
      model (Kumosinski et al., 1993). Two other crosslinks each connected 2 residues
      that are much closer together, according to the model, than the maximum length of
      the crosslink. However, one of the crosslinks apparently connected 2 residues
      that are predicted by the model to be 16.7 A farther apart than the crosslink's
      stretched length. This disparity might be explained by structural flexibility.
      The structure expressed by the model is probably one of several energetically
      favorable conformations of the beta-CN molecule, whose structure is best
      described as rheomorphic rather than either a fixed structure or a random coil.

PMID- 15483146
TI  - Calcium, zinc, and iron bioavailabilities from a commercial human milk fortifier:
      a comparison study.
AB  - Adding human milk fortifiers (HMF) to human milk (HM) is one way of overcoming
      the nutrient deficits found in the latter. In this study, the bioavailabilities
      of calcium, zinc, and iron in S-26/SMA HMF added to HM were compared with those
      in HM fortified with various bovine milk proteins: alpha-lactalbumin, colostrum,
      caseinate, casein phosphopeptides, and whey protein concentrate. The
      bioavailability of each mineral was assessed using an in vitro digestion/Caco-2
      cell culture model. Calcium and zinc uptake by the cells was traced with
      radioisotopes; iron uptake was assessed via cell ferritin levels. Samples were
      prepared on an equal protein content basis and with added calcium, but no zinc or
      iron was added. Results revealed that calcium uptake from HM + S-26/SMA was not
      different from any of the HM fortified with the bovine milk proteins, except for
      unfortified HM and HM + colostrum in which calcium uptake was significantly lower
      (-89 and -38%, respectively). Uptake of zinc and iron were significantly higher
      for HM + S-26/SMA than for the other HM + fortifiers.

PMID- 15483148
TI  - Influence of brine concentration, brine temperature, and presalting on early gas
      defects in raw milk pasta filata cheese.
AB  - Thirty-one 3.8-kg blocks of Ragusano cheese were made on each of 6 d starting
      with a different batch of raw milk on each day. On d 1, 3, and 5, cheeses were
      not presalted and on d 2, 4, and 6, all cheeses were presalted. Before brine
      salting, one of the 31 blocks of cheese was selected at random for analysis
      (i.e., at d 0). The remaining 30 blocks were randomly divided into 2 batches of
      15 blocks each, one group was placed in 18% brine, and the other group was placed
      in saturated brine. For the 15 blocks within each of the 2 brine concentrations,
      5 blocks each were placed in brine tanks at 12, 15, and 18 degrees C. Cheese
      blocks were sampled immediately before brine salting (d 0) and after 1, 4, 8, 16,
      and 24 d of brine salting. Presalting the curd with 2% added salt before
      stretching reduced the coliform count in the cheese by 1.41 log and resulted in a
      major reduction in early gas formation. Across all treatments in the present
      study, the average reduction in gas formation due to presalting was 75%. Reducing
      brine temperature had the second largest impact on reducing gas production, but
      did not reduce the coliform count in the cheese. Reducing brine temperature from
      18 to 12 degrees C made a larger reduction in early gas formation in cheeses that
      were not presalted (from 6.8 to 1.8% gas holes, respectively) than in cheeses
      that were presalted (from 1.9 to 0.5% gas holes, respectively). To achieve the
      same absolute level of gas production in the nonpre-salted cheese as was achieved
      in presalted cheese in combination with 18 degrees C brine, the brine temperature
      for the nonpresalted cheese had to be lowered from 18 to 12 degrees C. Reducing
      brine concentration, although effective at increasing the rate of salt
      penetration into the block, did not have any impact on coliform count and had
      minimal impact on reducing gas production. The condition where reducing brine
      concentration was able to make a reduction in gas production was for cheeses that
      were not presalted and brined at 18 degrees C. Presalting is a very simple and
      practical approach to reducing the problem of early gas formation in combination
      with strategies to improve milk quality and cheese making conditions. Further
      work is needed to understand the impact of different levels of presalting on
      death of coliforms and gas production in the cheese.

PMID- 15483149
TI  - Resynchronizing estrus and ovulation after not-pregnant diagnosis and various
      ovarian states including cysts.
AB  - We compared outcomes of 2 protocols used to resynchronize estrus and ovulation in
      dairy females after a not-pregnant diagnosis. Nulliparous heifers and lactating
      cows in which artificial insemination (AI) occurred 41 +/- 1 d earlier were
      presented every 2 to 3 wk for pregnancy diagnosis by using ultrasonography.
      Ovaries were scanned, follicles were mapped and sized, presence of corpus luteum
      was noted, and GnRH was injected (d 0). Females were assigned randomly to receive
      PGF(2alpha) 7 d later (d 7) and then either received estradiol cypionate (ECP) 24
      h after PGF(2alpha) (d 8; Heatsynch; n = 230) or a second GnRH injection 48 h
      after PGF(2alpha) (d 9; Ovsynch; n = 224). Those detected in estrus since their
      not-pregnant diagnosis were inseminated, whereas the remainder received a timed
      AI (TAI) between 65 and 74 h after PGF(2alpha). Ovarian scans and blood collected
      before injections for progesterone analysis were used to classify 4 ovarian
      status groups: anestrus, follicular cysts, luteal cysts, and cycling, plus an
      unknown group of females in which no blood sampling or ovarian scans were made.
      Few females (5.1%) were inseminated between not-pregnant diagnosis and d 8. On d
      10, more ECP- than GnRH-treated females were inseminated after detected estrus
      (24 vs. 6%). Overall, more Ovsynch than Heatsynch females received a TAI (82 vs.
      62%). Conception rates tended to be greater for females inseminated after estrus
      (37%) than after TAI (29%), particularly for those treated with Heatsynch (41 vs.
      27%) than with Ovsynch (33 vs. 31%). Those inseminated after estrus conceived 31
      +/- 8 d sooner than those receiving the TAI. Conception rates for females having
      elevated progesterone 7 d after the not-pregnant diagnosis were greater than
      those having low progesterone in Heatsynch (42%; n = 133 vs. 25%; n = 55) and
      Ovsynch protocols (33%; n = 142 vs. 15%; n = 45), respectively. Conception rates
      were greater in nulliparous heifers than in lactating cows (43 vs. 28%)
      regardless of protocol used. Although overall pregnancy outcomes after a not
      pregnant diagnosis were similar in response to either the Ovsynch and Heatsynch
      protocols, inseminations performed after detected estrus before the scheduled TAI
      reduced days to eventual conception and tended to increase conception rates,
      particularly after Heatsynch.

PMID- 15483150
TI  - Effects of an injectable trace mineral supplement on first-service conception
      rate of dairy cows.
AB  - A total of 825 dairy cows from a commercial dairy farm in central California were
      used to evaluate effects of one or 2 doses of an injectable trace mineral
      supplement containing 20 mg/mL of zinc, 20 mg/mL of manganese, 5 mg/mL of
      selenium, and 10 mg/mL of copper on first-service conception rate. Cows were
      randomly allocated into treatment or control group to either a single dose
      (experiment 1) or a double dose (experiment 2) of injected supplement. Allocation
      was based on days in lactation for experiment 1 and the length of gestation
      periods for experiment 2. In experiment 1, cows 38 to 45 d in lactation (n = 190)
      received a single dose of 5 mL of injected supplement. Similar cows were used as
      controls (n = 227). In experiment 2, cows and pregnant heifers received an
      initial injection of 5 mL of the mineral supplement from 2 to 3 wk precalving (n
      = 186). An equal dose was repeated 38 to 45 d in lactation. A similar group of
      cows and pregnant heifers served as controls for experiment 2 (n = 222). Health
      and reproductive events postcalving were recorded. In experiment 1, the odds of
      first-service conception were not significantly different for cows receiving a
      one-dose regimen of minerals compared with untreated control cows; conception
      rates were 26.8 and 27.5% for experiment 1 treatment and control groups,
      respectively. In experiment 1, the odds of first-service conception were
      significantly lower (odds ratio = 0.66) for cows and heifers given the 2-dose
      regimen of minerals compared with untreated controls; overall conception rates
      were 21.5 and 31.5% for experiment 2 treatment and control groups, respectively.
      In this intensively managed dairy herd, a single dose of injected trace minerals
      before breeding had no beneficial effects on first-service conception rate.
      However, dairy cows receiving a dose of trace minerals before calving and another
      dose before breeding had lower conception at first service.

PMID- 15483151
TI  - Impact of early lactation somatic cell count in heifers on somatic cell counts
      over the first lactation.
AB  - The objective of this study was to estimate the impact of somatic cell count in
      early lactation (SCCel) from Belgian dairy heifers on test-day somatic cell count
      (SCC) in first lactation. Geometric mean SCCel [5 to 14 d in milk (DIM)] of the
      14,766 available samples was 104,000 cells/mL, and decreased from 178,000 at 5
      DIM to 74,000 cells/mL at 14 DIM. Proportion of SCCel >200,000 cells/mL was 27.5.
      Heifers calving in the period April-June had highest SCCel. In total, 117,496
      monthly SCC were measured. A multilevel regression analysis revealed that an
      increase of the natural log-transformed SCCel (LnSCCel) by one unit on average
      resulted in an increase of test-day natural log-transformed SCC (LnSCC) by 0.22
      unit. The impact of LnSCCel on LnSCC depended on when LnSCCel was measured; an
      elevated LnSCCel at 14 DIM was more consequential than an equally elevated
      LnSCCel at 5 DIM. The probability of having a test-day SCC >200,000 cells/mL
      during the first lactation, also increased with an increasing LnSCCel. The
      negative effect of an elevated LnSCCel was still present, although to a lesser
      extent, in heifers with a second test-day SCC <or=50,000 cells/mL. This study
      indicates that udder health problems in heifers in early lactation have a high
      prevalence and stresses that heifers should have a low SCCel, because an elevated
      SCCel will negatively influence test-day SCC during the whole first lactation.

PMID- 15483152
TI  - Effects of photoperiod during the dry period on cellular immune function of dairy
      cows.
AB  - Recent studies suggest that exposure of cattle to photoperiod can influence
      immune function. The objective of this study was to determine whether treatment
      of cows with short day photoperiod (SDPP; 8 h light: 16 h darkness) during the
      dry period alters immune function, relative to cows subjected to a long day
      photoperiod (LDPP; 16 h light: 8 h darkness). Multiparous Holstein cows (n = 39)
      were dried 62 d before calving and exposed to photoperiod treatment until
      parturition; thereafter, cows were exposed to natural photoperiod. General health
      was monitored weekly during the dry period and cellular immune function was
      examined monthly during the dry period and at calving. Concentrations of
      prolactin and cortisol were measured from 10 d before calving to 2 d after
      calving. The periparturient prolactin surge in plasma was greater in LDPP cows
      (54.6 ng/ mL) than SDPP (22.4 ng/mL). Relative to LDPP cows, neutrophil
      chemotaxis and lymphocyte proliferation were enhanced in SDPP cows during the dry
      period. Neutrophil chemotaxis averaged 142.5 and 178.8 cells/ well during the dry
      period for LDPP and SDPP, respectively. Lymphocyte proliferation during the dry
      period averaged 197.6 and 326.5% for LDPP and SDPP cows, respectively.
      Physiological characteristics of the cows were not affected by treatment during
      the dry period. However, differences between treatments were observed within 2 d
      of parturition. Potential implications of photoperiod management for cow health
      and well-being merit further investigation.

PMID- 15483153
TI  - Reproductive performance and milk production of Assaf sheep in an intensive
      management system.
AB  - The Assaf breed of dairy sheep, a stabilized cross of the Awassi and East
      Friesian breeds, has replaced the Awassi as the breed of choice in its country of
      origin, Israel, and has spread to other Mediterranean countries. In Israel the
      Assaf breed is managed under an intensive production system involving weaning
      lambs at birth, rearing them artificially, and milking ewes after parturition.
      There are several breeding periods in the year when ewes are mated following
      hormonally synchronized estrus. Records of 18,976 lactations from 5 farms were
      analyzed to investigate factors that influenced Assaf milk and reproductive
      performance. Lactation curves were fitted to each lactation, and a range of
      parameters and calculated values were analyzed. Daily milk yield records also
      were analyzed to describe a typical Assaf lactation and compared with those of
      the Awassi breed. Factors affecting age at first lambing also were studied. An
      average Assaf ewe kept under this intensive management regimen was found to
      produce 334 L of milk during a 173-d lactation. Mean litter size was 1.57
      lambs/ewe lambing, and lambing interval was 272 d. Milk production was affected
      by litter size, with twin- and triplet-bearing ewes producing approximately 20 L
      more milk per lactation than single-bearing ewes. Day length was the major
      environmental variable influencing milk yield. The difference between midsummer
      and midwinter day lengths accounted for a difference in daily milk yield of 0.44
      L in favor of summer. Ewe lambs that were mated for the first time at later ages
      produced more lambs and more milk due to greater early lactation characteristics.
      Milk production was found to be negatively associated with subsequent
      reproductive performance. Comparing these results with those from an earlier
      study in the Awassi breed, the Assaf was found to produce less milk during a
      shorter lactation than the Awassi, but its greater litter size made it a more
      profitable breed.

PMID- 15483154
TI  - Timed artificial insemination with estradiol cypionate or insemination at estrus
      in high-producing dairy cows.
AB  - A total of 799 Holstein cows from 3 herds were randomly assigned at 37 +/- 3 d in
      milk (DIM) to timed artificial insemination (AI) or insemination at detected
      estrus. Cows were presynchronized with injections of PGF(2alpha) at 37 and 51
      DIM. At 65 DIM, cows received an injection of GnRH, followed 7 d later by
      PGF(2alpha). Cows in the estrus-detected group were inseminated after being
      observed in estrus during the 7 d after the last PGF(2alpha). Cows in the timed
      AI group received an injection of 1 mg of estradiol cypionate (ECP) 24 h after
      the last PGF(2alpha). If detected in estrus <or= 24 h after ECP, cows were
      inseminated then or at a fixed time 48 h after ECP. Pregnancy was diagnosed by
      ultrasonography at 30 d and by palpation at 44 and 58 d after AI. Plasma
      progesterone was measured in 4 samples per cow collected on days of 1) second
      PGF(2alpha), 2) GnRH, 3) third PGF(2alpha), and 4) 48 h after third PGF(2alpha).
      Cows were classified as cyclic or anovulatory based on progesterone
      concentrations in samples 1 and 2. Similarly, cows were classified according to
      progesterone concentrations in samples 2, 3, and 4 (H = >or=1 ng/mL; L = <1
      ng/mL), resulting in 8 combinations (LLL, LHL, LLH, LHH, HHH, HHL, HLH, and HLL).
      Conception rates and pregnancy rates were higher for cows in the timed AI group
      than in the estrus-detected group at 30, 44, and 58 d (e.g., at 58 d, pregnancy
      rates were 42.2% for multiparous cows or 34.4% for primiparous cows in the group
      receiving ECP and timed AI compared with only 20.8 or 18.8% for respective parity
      subgroups for the treatment group inseminated only at detected estrus). Pregnancy
      losses were 11.5% from 30 to 58 d and did not differ between treatments. Cyclic
      cows within both treatments had higher estrous responses, conception rates, and
      pregnancy rates. Cows that responded to presynchronization and to luteolysis
      (HHL) had the highest conception and pregnancy rates, followed by cows classified
      as LHL. Use of 1 mg of ECP to induce ovulation as part of a synchrony regimen
      improved reproduction at first postpartum insemination in dairy cows.

PMID- 15483155
TI  - Neutrophils in the war against Staphylococcus aureus: predator-prey models to the
      rescue.
AB  - To address the question of whether a minimum concentration of blood neutrophils
      is necessary to decrease Staphylococcus aureus concentration in mastitic milk,
      literature was searched for studies in which neutrophils were incubated with
      Staph. aureus. Different mathematical models that describe the changes in Staph.
      aureus population as a function of neutrophilic concentrations were applied to
      the collected data. The best fitted model established (1) that the rate of
      bacterial killing depended on the ratio of neutrophils to bacteria with
      neutrophilic attack rate accelerating at first before decelerating as the ratio
      increases, and (2) that neutrophil concentration should be within a limited range
      to trigger a decline in the bacterial population. Outcomes of this model are
      supported by what is known about neutrophilic functions and laboratory findings
      in bovine and human neutrophils. These results may be of assistance in setting
      selection goals for a better resilience to Staph. aureus mastitis in dairy
      cattle. Indeed, an optimal neutrophilic concentration appears to exist for
      successful clearance of Staph. aureus infection, which is neither the lowest nor
      the highest one.

PMID- 15483156
TI  - Evaluation and use of three cowside tests for detection of subclinical ketosis in
      early postpartum cows.
AB  - The objective was to evaluate the performance of 3 cowside diagnostic tests for
      detection of subclinical ketosis, defined as a serum beta-hydroxybutyrate (BHBA)
      concentration >or=1400 micromol/L. On 16 d over a 5-mo period, samples of serum,
      milk, and urine were collected on a large dairy facility from cows of all
      parities between 2 and 15 DIM. The sample proportion of subclinical ketosis was
      7.6% (n = 859 samples from 545 cows). The KetoCheck powder (Great States Animal
      Health, St. Joseph, MO) detecting acetoacetate in milk samples was very specific
      (99%) but poorly sensitive (41%). Respective sensitivities and specificities of
      the Ketostix strip detecting acetoacetate in urine samples (Bayer Corporation,
      Elkhart, IN) were 78 and 96% with a cut-off point of "small", or 49 and 99% with
      a cut-off of "moderate." The KetoTest strip (Sanwa Kagaku Kenkyusho Co. Ltd.,
      Nagoya, Japan) using milk samples had a sensitivity and specificity of 73 and 96%
      with a cut-off of 100 micromol of BHBA/L or 27 and 99% with a cut-off of 200
      micromol of BHBA/L. On average, use of the Ketostix at the "small" cut-off point
      or the KetoTest at 100 micromol/L would result in no more than 3 or 4 false
      positives per 100 cows screened, with prevalence levels ranging from 5 to 30%,
      whereas the number of false negatives would range from one false negative at 5%
      prevalence to 7 or 8 false negatives at 30% prevalence. Either the Ketostix or
      KetoTest strips would provide acceptable results for screening individual cows on
      commercial dairies to detect subclinical ketosis. Over this prevalence range, the
      KetoCheck powder test would have limited application as a screening test. Despite
      only one false positive per 100 animals screened, false negatives resulting from
      screening with the KetoCheck test would be too frequent, ranging from 3 false
      negatives at 5% prevalence to 18 at 30% prevalence in a population of 100 tested
      cows. Finally, given their relative imprecision, use of any of these individual
      cowside tests to estimate herd prevalence must be done cautiously, especially
      when only a small number of animals are sampled.

PMID- 15483157
TI  - Growth performance and health of dairy calves bedded with different types of
      materials.
AB  - Granite fines, sand, rice hulls, long wheat straw, and wood shavings were
      compared as bedding for 60 female dairy calves. Growth, health, stress indices,
      and behavior of newly born calves, along with physical characteristics and
      bacterial counts of bedding, were evaluated for 42 d during August to October,
      2002. Overall average daily gain and dry matter intake of calves did not differ
      due to bedding type, although during wk 2 calves housed on rice hulls had the
      greatest dry matter intake and those housed on wood shavings had the lowest.
      During wk 2, calves housed on granite fines and sand were treated more often for
      scours, and calves housed on long wheat straw received the fewest antibiotic
      treatments (week by bedding material interaction). Granite fines formed a harder
      surface than other bedding, and calves housed on granite fines scored the
      dirtiest. When bedding materials were evaluated, sand was scored to be the
      dirtiest, while pens bedded with rice hulls, long wheat straw, and wood shavings
      scored cleaner. Long wheat straw had the warmest surface temperature, and rice
      hulls and wood shavings were warmer than granite fines and sand. Serum cortisol,
      alpha(1)-acid glycoprotein, immunoglobulin G concentrations, and the
      neutrophil:lymphocyte ratio were not affected by bedding type. On d 0, coliform
      counts were greatest in rice hulls. After use, coliform counts were greatest in
      long wheat straw (week by bedding material interaction). On d 42, the
      concentration of ammonia at 10 cm above the bedding was lowest for long wheat
      straw. Growth performance of calves bedded for 42 d with 5 bedding types did not
      differ; however, the number of antibiotic treatments given for scours was
      greatest on granite fines and sand; coliform counts in the bedding were highest
      in rice hulls before use and in long wheat straw after 42 d of use.

PMID- 15483158
TI  - Effect of modified dry period lengths and bovine somatotropin on yield and
      composition of milk from dairy cows.
AB  - Dry periods of 40 to 60 d have been an industry standard because dry periods <40
      d have resulted in reduced milk yields in the subsequent lactation by 10 to 30%.
      However, recent research has demonstrated no production losses for cows given a
      30-d dry period. The current study evaluated milk production effects of shortened
      or omitted dry periods for cows at mature-equivalent production >12,000 kg of
      milk and treated with bovine somatotropin (bST). The study used 2 commercial
      dairies and one university dairy and included 4 treatments. Five multiparous and
      5 primiparous cows from each farm were assigned to each treatment: 1) 60-d dry
      period, label use of bST (60DD); 2) 30-d dry period, label use of bST (30DD); 3)
      continuous milking, label use of bST (CMLST); and 4) continuous milking with
      continuous use of bST (CMCST). Per label, bST use started at 57 to 70 d in milk
      and ended 14 d before drying (60DD and 30DD) or expected calving date (CMLST). In
      primiparous cows, average milk yields during the first 17 wk of lactation were
      reduced for cows on treatments 30DD, CMLST, and CMCST vs. the 60DD treatment.
      (38.3, 35.1, and 37.5 vs. 44.1 +/- 1.3 kg/d, respectively). For multiparous cows,
      respective milk yields did not differ (46.6, 43.4, 46.5, and 47.7 +/- 2.1 kg/d).
      Shortened or omitted dry periods may impede mammary growth in primiparous cows,
      resulting in reduced milk yield in the subsequent lactation. In contrast, a
      shortened or omitted dry period with either bST protocol did not alter production
      in multiparous cows treated with bST. Quality aspects of prepartum milk and
      colostrum require additional characterization. For multiparous cows, milk income
      generated for short dry periods or for continuous milking might increase their
      profitability. At 17 wk of the subsequent lactation, estimates of the cumulative
      net margins of multiparous cows on the 30DD treatment and continuous milking
      treatments exceeded those of cows on the 60DD treatment by 40 dollars to 60
      dollars per cow.

PMID- 15483159
TI  - Effect of bovine somatotropin and rumen-undegradable protein on mammary growth of
      prepubertal dairy heifers and subsequent milk production.
AB  - Rapid body growth during the prepubertal period may be associated with reductions
      in mammary parenchymal growth and subsequent milk yield. The objective of this
      study was to test effects of dietary rumen-undegradable protein (RUP) and
      administration of recombinant bovine somatotropin (bST) during the prepubertal
      period on mammary growth and milk yield of dairy heifers. Seventy-two Holstein
      heifers were used in the experiment. At 90 d of age, 8 heifers were slaughtered
      before initiation of treatment. Remaining heifers were assigned randomly to 1 of
      4 treatments. Treatments consisted of a control diet (5.9% RUP, 14.9% CP, DM
      basis) or RUP-supplemented diet (control diet plus 2% added RUP) with or without
      0.1 mg of bST/kg of BW per day applied in a 2 x 2 factorial design. A total of 6
      heifers per treatment (3 each at 5 and 10 mo of age) were slaughtered for mammary
      tissue analysis. Remaining heifers were bred to evaluate impact of treatment on
      subsequent milk yield and composition. Mammary parenchymal growth was not
      affected by RUP or bST treatment. Total parenchymal mass increased from 16 to 364
      g, and parenchymal DNA from 58 to 1022 mg from 3 to 10 mo of age, respectively.
      Furthermore, number of mammary epithelial cells likely was not affected by diet
      or bST because the epithelial cell proliferation index, assessed by Ki-67
      labeling, was not affected by treatment, nor was total parenchymal DNA and lipid
      content. Neither deleterious effects of increased rates of gain nor positive
      effects of bST were evident in prepubertal mammary growth. Subsequent milk
      production and composition was not different among treatments.

PMID- 15483160
TI  - Cow-level prevalence of paratuberculosis in culled dairy cows in Atlantic Canada
      and Maine.
AB  - The prevalence of Mycobacterium avium ssp. paratuberculosis (Mptb) in culled
      dairy cattle in Eastern Canada and Maine was determined to be 16.1% (95%
      confidence interval 13.8 to 18.3%) based on a systematic random sample of
      abattoir cattle. Mesenteric lymph nodes and ileum from 984 cows were examined by
      histologic and bacteriologic methods. Histological testing was far less sensitive
      than bacteriologic methods for detecting infected cattle. A seasonal pattern of
      positive cows was also detected, with the highest proportion of cows being Mptb
      positive in June (42.5%). Overall, body condition score was not associated with
      prevalence of Mptb isolation.

PMID- 15483161
TI  - Haptoglobin concentrations in blood and milk after endotoxin challenge and
      quantification of mammary Hp mRNA expression.
AB  - Haptoglobin (Hp), an acute phase protein mostly secreted by the liver, is an
      inflammatory marker. To use the full diagnostic potential of Hp measurements for
      mastitis, we developed and validated an ELISA sensitive to quantify even basal
      and subclinical concentrations in both blood and milk. Bovine Hp was purified
      from serum and was used as a standard and to generate polyclonal antiserum. The
      limit of detection was 0.07 microg of Hp/mL. From 6 cows challenged by
      intracisternal injection of lipopolysaccharide (LPS) into one quarter, blood
      samples were collected 0, 3, 6, 9, and 12 h after LPS administration. Milk
      samples from the treated and from the contralateral quarters were collected 0, 3,
      6, 9, 12, 24, 36, 48, and 60 h after LPS administration. Haptoglobin
      concentrations in blood were increased above basal at 9 h, whereas milk Hp
      concentration increased 3 h after LPS administration. We therefore evaluated Hp
      mRNA synthesis within the mammary gland and specifically demonstrated Hp mRNA
      expression in parenchymal tissue, in tissue around the cisternal milk ducts and
      also in teat tissue by RT-PCR. Haptoglobin mRNA expression was then
      quantitatively evaluated by real-time RT-PCR in mammary biopsies collected from
      the treated and the control quarter before, and 3, 6, 9, and 12 h after LPS
      challenge from 6 other cows. Haptoglobin mRNA expression in the treated vs. the
      control quarters was different. The relation between mammary Hp expression and
      milk Hp concentrations needs further investigation, but the results suggest good
      diagnostic potential of this parameter for mastitis.

PMID- 15483162
TI  - Technical note: a rapid lipid separation method for determining fatty acid
      composition of milk.
AB  - A rapid method for milk lipid separation followed by transmethylation to produce
      fatty acid methyl esters from bovine milk samples is presented. Fat is separated
      by a nonsolvent method using centrifugation. The method was compared with the
      popular hexane:isopropanol solvent extraction method, and fatty acid proportions
      were statistically identical for both methods. In 108 replicates, variance
      accounted for by using the 2 methods was of a similar magnitude to variance due
      to repeat separations or repeat injections onto the gas chromatography column. It
      is concluded that the proposed method is accurate, simple, rapid, safe,
      economical, and especially suitable for large numbers of samples.

PMID- 15483163
TI  - Study of the lactation curve in dairy cattle on farms in central Mexico.
AB  - Accurate knowledge of lactation curves has an important relevance to management
      and research of dairy production systems. A number of equations have been
      proposed to describe the lactation curve, the most widely applied being the gamma
      equation. The objective of this work was to compare and evaluate candidate
      functions for their predictive ability in describing lactation curves from
      central Mexican dairy cows reared under 2 contrasting management systems. Five
      equations were considered: Gaines (exponential decay), Wood (gamma equation),
      Rook (Michaelis-Menten xexponential), and 2 more mechanistic ones (Dijkstra and
      Pollott). A database consisting of 701 and 1283 records of cows in small-scale
      and intensive systems, respectively, was used in the analysis. Before analysis,
      the database was divided into 6 groups representing first, second, and third and
      higher parity cows in both systems. In all cases except second and above parity
      cows in small-scale systems, all models improved on the Gaines equation. The Wood
      equation explained much of the variation, but its parameters do not have direct
      biological interpretation. Although the Rook equation fitted the data well, some
      of the parameter estimates were not significant. The Dijkstra equation
      consistently gave better predictions, and its parameters were usually
      statistically significant and lend themselves to physiological interpretation. As
      such, the differences between systems and parity could be explained due to
      variations in theoretical initial milk production at parturition, specific rates
      of secretory cell proliferation and death, and rate of decay, all of which are
      parameters in the model. The Pollott equation, although containing the most
      biology, was found to be over-parameterized and resulted in nonsignificant
      parameter estimates. For central Mexican dairy cows, the Dijkstra equation was
      the best option to use in describing the lactation curve.

PMID- 15483164
TI  - Milk fat responses to a change in diet fermentability vary by production level in
      dairy cattle.
AB  - The effects of dietary starch fermentability on plasma metabolites and hormones,
      milk production, and milk fatty acid profile were evaluated in a crossover study.
      Thirty-two multiparous Holstein cows (121 +/- 48 d in milk, 41 +/- 9 kg/d 3.5%
      fat-corrected milk [FCM]; mean +/- SD) were randomly assigned to treatment
      sequence and were fed a diet intermediate to the treatments during an initial 21
      d period. Treatments were dry ground corn grain (DG) and high moisture corn (HM)
      harvested from the same field. Treatment periods were 14 d, with the final 4 d
      used for data and sample collection. Diets included corn silage and alfalfa
      haylage at a 2:1 ratio and were ~26% neutral detergent fiber, 16.5% crude
      protein, 32% starch, and 3.5% fatty acids. High moisture corn increased plasma
      glucose, nonesterified fatty acid, and triglyceride concentrations, but treatment
      had no consistent effect on yield of milk or FCM. High moisture corn increased
      trans C(18:1) concentrations at an increasing rate as production level decreased
      across cows, and milk fat depression was evident in cows below approximately 40
      kg/d FCM yield. In contrast, production level had little influence on milk trans
      C(18:1) concentration for DG. Milk trans C(18:1) concentration was negatively
      correlated with milk fat concentration, as was trans-9 C(18:1), trans-10 C(18:1),
      and cis-9, trans-11 C(18:2). Concentration of trans-10, cis-12 C(18:2) was not
      correlated with milk fat concentration. Production level may influence
      biohydrogenation patterns and trans C(18:1) production because of differences in
      rumen environment; rumen pH and dilution rate can alter metabolism and
      populations of rumen microbes. Diets with highly fermentable starch sources and
      without supplemental dietary polyunsaturated fatty acids can induce milk fat
      depression in lower-producing cows, likely because of increased production of
      trans C(18:1) fatty acids.

PMID- 15483165
TI  - Lactation performance and feeding behavior of dairy cows supplemented via
      automatic feeders with soy hulls or barley based pellets.
AB  - The potential of soy hulls to replace barley grain in pellets supplemented to
      lactating cows was measured in automatic concentrate feeders (ACF). Thirty-six
      cows were divided into 2 equal groups and fed 1 of the 2 experimental pellet
      supplements individually for 7 wk. All cows were group-fed a basic mixture along
      the feeding lane (~64% of dietary DM) plus a pelleted additive containing 50%
      barley or soy hulls as barley replacer, fed individually to each cow via the ACF
      in 6 feeding windows. Extent and rate of in vitro DM digestibility were similar
      for both types of pellets; however, NDF content and digestibility were higher in
      the soy hulls pellets. Average number of rewarded cow visits at the ACF, pellets
      intake per meal, and accumulated intake of pellets (8.64 kg/d DM) were similar in
      the 2 experimental groups. Most pellets were consumed during day and night in the
      first 2 h after feeding windows were opened. Total visits per day in the ACF and
      the maximal interval between visits were similar for the 2 pellets, indicating
      similar attractiveness to the cow. Predicted intake of the basic mixture was
      similar in both groups (14.8 to 15.1 kg of DM/d). Higher milk fat content was
      observed in the soy hulls-fed cows, whereas higher milk protein content was found
      in the barley-fed cows. Milk yield was similar in both groups. Data suggest that
      replacement of barley pellets with soy hulls pellets may slightly enhance milk
      fat while reducing milk protein production for dairy herds using automatic
      milking systems.

PMID- 15483166
TI  - Measures of bone mineral content in mature dairy cows.
AB  - The objectives of this investigation were to assess the relationship between
      chemical measures and imaging estimates (radiographic photometry and dual-energy
      x-ray absorptiometry) of bone mineral content in dairy cows and to evaluate the
      effects of parity, stage of lactation, and site of measurement (fused third and
      fourth metacarpal bone vs. caudal vertebrae 14 and 15) on bone mineral content.
      In a preliminary study, the caudal vertebrae were excised from 33 cows following
      slaughter. Samples were analyzed by radiographic photometry and then analyzed for
      mineral content chemically. In a second experiment, the caudal vertebrae and
      right front metacarpal (sample pairs) were excised from 107 Holstein cull cows
      following slaughter. Parity and days in milk (DIM) of the donor animals were
      obtained for 43 pairs of samples. Samples were grouped by parity (1, 2, 3, and
      >or=4) stage of lactation (Stage 1: <90 DIM, Stage 2: 90 to 150 DIM, Stage 3: 151
      to 250 DIM, and Stage 4: >250 DIM). Samples were analyzed by radiographic
      photometry and dual-energy x-ray absorptiometry and then analyzed for mineral
      content chemically. In both experiments, the relationship between mineral content
      estimated via the imaging techniques and mineral content measured chemically was
      poor, likely because of the relative maturity of animals in the sample set and
      lack of variation in mineral content. Ash content was higher in the metacarpal
      than in the caudal vertebrae, as were concentrations of Mg (expressed as a
      proportion of bone ash). No effects of stage of lactation were observed on bone
      mineral in the caudal vertebrae, but in the metacarpal, P content (proportion of
      total mineral) was highest in second lactation cows. Total bone mineral content
      (ash) was not affected by parity in the metacarpal or caudal vertebra, but Ca and
      P content of the metacarpal increased with parity. Noninvasive imaging techniques
      are not sufficiently sensitive to detect changes in mineral content or
      composition of mature cows, and only modest changes in bone mineral were observed
      with stage of lactation and parity.

PMID- 15483167
TI  - Prediction of fermentation parameters in grass and corn silage by near infrared
      spectroscopy.
AB  - Prediction models were developed for determination of lactic acid (Lac), acetic
      acid (HAc), pH, NH(3) N, and ethanol (EtOH) in grass and corn silages by near
      infrared (NIR) spectroscopy. Generally, Lac, pH, and NH(3) N concentrations in
      original sample material could be determined with a better accuracy when NIR
      measurements were performed on dried material rather than on wet material. The
      difference could only partly be explained by the repeatability error of NIR
      measurements for compounds stable with respect to drying. The HAc concentration
      was determined slightly more accurately when measurements were performed on wet
      material. The respective ratios between analytical concentration range expressed
      as standard deviation and the root mean square error of cross validation (RMSECV)
      were 4.9, 2.0, 3.7, and 3.1 for Lac, HAc, pH, and NH(3) N measured on dried grass
      silage, and 3.3 for EtOH measured on wet grass silage. The corresponding standard
      deviation:RMSECV for corn silage were 4.7, 1.9, 2.4, 2.9, and 4.0. The content of
      Lac was affected only slightly by drying at 80 degrees C, whereas the effects on
      NH(3) N and HAc were more pronounced, depending on silage type.

PMID- 15483168
TI  - Changes in milk fat in response to dietary supplementation with calcium salts of
      trans-18:1 or conjugated linoleic fatty acids in lactating dairy cows.
AB  - Milk fat was investigated in lactating dairy cows fed diets supplemented with Ca
      salts of trans fatty acids (Ca-tFA) or Ca salts of conjugated linoleic acids (Ca
      CLA). Forty-five Holstein cows (115 days in milk) were fed a control diet (51%
      forage; dry matter basis) supplemented with 400 g of EnerG II (Ca salts of palm
      oil fatty acids) for 2 wk; subsequently, 5 groups of 9 cows each were assigned
      for 4 wk to the control diet or diets containing 100 g of Ca-CLA or 100, 200, or
      400 g of Ca-tFA in a randomized block design. Treatments had no effect on dry
      matter intake, milk production, protein, lactose, or somatic cell count. Milk fat
      percentage was reduced from 3.39% in controls to 3.30, 3.04, and 2.98%,
      respectively, by the Ca-tFA diets and to 2.54% by the Ca-CLA diet. Milk fat yield
      (1.24 kg/d in controls) was decreased by 60, 130, and 190 g/d with increasing
      dose of Ca-tFA and by 290 g/d with the Ca-CLA supplement. Consistent with
      increased endogenous synthesis of cis-9-containing CLA from precursors provided
      by the Ca-tFA diets, total CLA were similar in milk of cows fed Ca-CLA or Ca-tFA.
      Compared with controls, the Ca-CLA diet increased trans-10, cis-12-18:2 yield in
      milk, without altering levels of trans-18:1 isomers. In contrast, yields of most
      trans-18:1 isomers were elevated in milk of cows fed Ca-tFA diets, whereas yields
      of trans-10, cis-12-18:2 remained similar to control values. We conclude that
      milk fat depression can occur without an increase in trans-10, cis-12-18:2 in
      milk and that other components, perhaps the trans-10-18:1 isomer, may be
      involved.

PMID- 15483169
TI  - In vitro generation and stability of the lactokinin beta-lactoglobulin fragment
      (142-148).
AB  - The objectives of this study were to investigate the generation of beta
      lactoglobulin fragment (142-148) (beta-LG f(142-148) during the hydrolysis of
      whey proteins, and the in vitro stability of this fragment upon incubation with
      gastrointestinal and serum proteinases and peptidases. An enzyme immunoassay
      (EIA) protocol was developed for the quantification of beta-LG f(142-148) in whey
      protein hydrolysates and in human blood serum. The minimum detection limit was 3
      ng/mL. The level of the peptide in whey protein hydrolysates was influenced by
      the degree of hydrolysis (DH). As expected, highest levels of this peptide were
      found in hydrolysates generated with trypsin. Sequential incubation of
      hydrolysates at different DH values with pepsin and Corolase PP, to simulate
      gastrointestinal digestion, generally resulted in the degradation of beta-LG
      f(142-148) as determined by EIA. Reversed-phase HPLC and angiotensin-I-converting
      enzyme (ACE) activity assays demonstrated that synthetic beta-LG f(142-148) was
      rapidly degraded upon incubation with human serum. Furthermore, beta-LG f(142
      148) could not be detected by EIA in the sera of 2 human volunteers following its
      oral ingestion or in sera from these volunteers subsequently spiked with beta-LG
      f(142-148). These in vitro results indicate that beta-LG f(142-148) is probably
      not sufficiently stable to gastrointestinal and serum proteinases and peptidases
      to act as an hypotensive agent in humans following oral ingestion. The in vitro
      methodology described herein has general application in evaluating the
      hypotensive potential of food protein-derived ACE inhibitory peptides.

PMID- 15483170
TI  - Small intestine and liver microsomal triacylglycerol transfer protein in the
      bovine and rat: effects of dietary coconut oil.
AB  - The bovine liver is characterized by a chronic low capacity to secrete
      triacylglycerols (TAG). In situations favoring their hepatic synthesis, such as
      coconut oil feeding, TAG accumulate, leading to a lipid infiltration in the liver
      of preruminant calves. To assess the possible role of the microsomal TAG transfer
      protein (MTP) in this phenomenon and to put into evidence a tissue-specific
      regulation in the bovine species, we compared by Western blot the content in both
      MTP subunits in the liver and in different portions of the small intestine in
      preruminant calves and in growing rats receiving coconut oil or beef tallow as
      the sole source of fat in the diet. The pattern of MTP distribution was similar
      between calf and rat tissues, the jejunum being the major site for both MTP
      expression and intestinal absorption of dietary lipid endproducts. Concentrations
      of the MTP large and small subunits were 10- to 20-fold lower and 2- to 3-fold
      lower, respectively, in calf than in rat tissues, including the liver. Coconut
      oil in the diets of calves and rats did not significantly affect the expression
      of MTP large subunits even though TAG content was strongly increased 12-fold in
      the calf liver. These results clearly indicated that calf liver handled fat
      metabolically in a manner different from rat liver. However, present experimental
      conditions did not allow proof that MTP was directly related to the accumulation
      of fat in calf liver.

PMID- 15483171
TI  - Bovine somatotropin and rumen-undegradable protein effects in prepubertal dairy
      heifers: effects on body composition and organ and tissue weights.
AB  - The objectives of this study were to determine the effect of recombinant bovine
      somatotropin (bST) and added dietary rumen undegradable protein (RUP) on organ
      and tissue weights and body composition in growing dairy heifers. Thirty-two
      Holstein heifers were in the experiment, 8 killed initially at 3 mo of age, with
      the remaining 24 Holstein heifers randomly assigned to treatments (n = 6)
      consisting of 0.1 mg/kg of body weight per day of bST and 2% added dietary RUP
      (dry matter basis) applied in a 2 x2 factorial design. A total of 6 heifers per
      treatment group (3 each at 5 and 10 mo of age), were slaughtered to determine
      body composition and organ masses. Feed intake measured from group intakes were
      increased by 0.25 and 0.35 kg/d with bST and RUP, respectively. Administration of
      bST tended to increase the weights of visceral organs including heart, kidney,
      and spleen by 16, 16, and 38%, respectively. At 10 mo of age, there was a trend
      for increased empty body weights (EBW) and non-carcass components for heifers
      treated with bST, but there were no effects of RUP. Body components and organ
      weights, expressed as a percentage of BW were not affected by RUP or bST.
      Somatotropin increased ash weight at 10 mo without affecting amounts of protein,
      fat, and energy. Rates of ash deposition between 3 and 10 mo of age were
      increased 7 and 4 g/d by bST and RUP, respectively. There were no treatment
      effects on rates of body fat, protein, and energy deposition. Bovine somatotropin
      and RUP altered the metabolism of growing heifers in a manner that was consistent
      with increased rates of skeletal growth. This suggests that nutritional and
      endocrine manipulations could increase growth rates of skeletal tissues without
      increasing fat deposition in prepubertal dairy heifers.

PMID- 15483172
TI  - Bovine somatotropin and rumen-undegradable protein effects on skeletal growth in
      prepubertal dairy heifers.
AB  - The objectives of this study were to determine the effects of dietary rumen
      undegradable protein (RUP) and bovine somatotropin (bST) during the period from
      weaning until puberty on body weight (BW) and skeletal growth rates and age at
      puberty. Fifty-one Holstein heifers at 90 d of age were randomly assigned to 4
      treatment groups consisting of 0.1 mg/kg BW per day of bST and 2% added dietary
      RUP (dry matter basis) applied in a 2 x 2 factorial design (n = 13 per group,
      except bST with no RUP group, n = 12). From 90 to 314 d, bST increased average
      daily gain (ADG) by 0.07 kg/d and BW by 16.2 kg, while added RUP increased ADG by
      0.10 kg/d and BW by 21.4 kg. Both bST and added RUP effects on BW and ADG were
      additive. Skeletal growth rates, as measured by withers height (WH) and hip
      height (HH) were increased by both bST and added RUP. Somatotropin and RUP
      increased WH by 1.8 and 2.7 cm and hip height by 2.5 and 4.0 cm, respectively, at
      314 d of age. Growth curves showed that added RUP effects on rates of BW, WH, and
      HH growth were greatest from 90 to 150 d age and diminished thereafter,
      suggesting that protein was limiting during this time period. Conversely, bST
      effects tended to be greater as the heifers approached puberty, but only in the
      presence of added RUP. Age at puberty was not affected by treatment, averaging
      314 d of age across treatments. From 314 to 644 d of age, rates of BW, WH, and HH
      growth were similar among treatment groups. However, treatment differences
      present at 314 d of age persisted through 644 d of age, more than 10 mo after
      treatments ceased. These results suggest that protein during the early
      postweaning period and bST during the 200 to 300 d of age period just prior to
      puberty could be used to accelerate simultaneous increases in both BW and
      skeletal growth rates in dairy heifers without reducing age at puberty.

PMID- 15483173
TI  - Effect of feeding whole, unprocessed sunflower seeds and flaxseed on milk
      production, milk composition, and prostaglandin secretion in dairy cows.
AB  - Four multiparous Holstein cows were used in a 4 x 4 Latin-square design
      experiment to study the effects of different fat sources on milk production and
      composition, N utilization, follicular development, and prostaglandin secretion.
      Cows were fed 4 total mixed rations (TMR) based either on calcium salts of palm
      oil (Megalac), whole flaxseed, whole sunflower seed, or no supplementary fat
      (control). Feed intake and digestibilities were generally similar among
      treatments, except that ether extract digestibility was the lowest for cows fed
      the control diet. Milk yields were greater for cows fed whole flaxseed and
      Megalac (32.1 and 31.5 kg/d, respectively) than for those fed sunflower seed and
      control (25.9 and 24.8 kg/d, respectively). Milk protein concentration was
      significantly lower for cows fed Megalac (3.68%) compared with those fed flaxseed
      (3.87%) or control (3.92%). Concentrations of n-3 fatty acids and the n-6 to n-3
      fatty acids ratio in milk were the highest and lowest, respectively, for cows fed
      whole flaxseed. There was an interaction between treatment and time for levels of
      13,14-dihydro-15-keto-PGF(2alpha) in plasma; they were greater 30 and 45 min
      after the oxytocin challenge for cows that were fed sunflower seed compared with
      those fed either Megalac, flaxseed, or control. Moreover, when concentrations of
      13,14-dihydro-15-keto-PGF(2alpha) in plasma were expressed as the area under the
      overall response curve from 0 to 120 min after the oxytocin injection, it tended
      to be greater for cows that were fed the sunflower diet compared with those fed
      either Megalac or flaxseed. In general, follicle dynamics were similar among
      treatments. These results suggest that feeding diets with high proportions of n-6
      fatty acids (61% of total fatty acids for the sunflower seed diet) tended to
      increase the secretion of series 2 prostaglandins in blood.

PMID- 15483174
TI  - Response of lactating dairy cows to diets containing wet corn gluten feed or a
      raw soybean hull-corn steep liquor pellet.
AB  - We evaluated effects of wet corn gluten feed (WCGF) and a novel product (SHSL)
      containing raw soybean hulls and corn steep liquor on performance and digestion
      in lactating dairy cows. In Experiment 1, 46 multiparous Holstein cows were
      assigned to control (C), WCGF (20% of diet DM), or SHSL (20% of diet DM). Diets
      were fed as a total mixed ration beginning after calving. The C diet contained
      (dry matter [DM] basis) 30% alfalfa hay, 15% corn silage, 32% corn, 9.3% whole
      cottonseed, 4.4% solvent soybean meal (SBM), and 3.3% expeller SBM. The WCGF
      replaced 10% alfalfa hay, 5% corn silage, and 5% corn grain, while expeller SBM
      replaced solvent SBM to maintain diet rumen undegradable protein. The SHSL
      replaced 10% alfalfa hay, 5% corn silage, 3% solvent SBM, and 2% corn. Dietary
      crude protein averaged 18.4%. Milk, energy-corrected milk (ECM), DM intake (DMI),
      and ECM/DMI were similar among diets during the first 13 wk of lactation. During
      wk 14 through 30 postpartum, WCGF and SHSL improved milk, ECM, milk component
      yield, and ECM/DMI. In Experiment 2, 6 cows were used to evaluate digestibility
      and rumen traits. Dry matter intake and total tract digestibilities of DM, fiber,
      and crude protein were not different among diets. Diets did not affect ruminal
      liquid dilution rate, pH, or concentrations of total volatile fatty acids or
      ammonia, but acetate:propionate was higher for C (3.38) than for WCGF (2.79) or
      SHSL (2.89). The WCGF and SHSL products can serve as alternative feedstuffs in
      diets fed to lactating dairy cattle.

PMID- 15483175
TI  - Effects of alfalfa particle size and specific gravity on chewing activity,
      digestibility, and performance of Holstein dairy cows.
AB  - Two experiments were carried out to test the effects of alfalfa particle size and
      functional specific gravity (FSG) on chewing activity, digestibility, rumen
      kinetics, and production of lactating dairy cows fed corn silage based rations.
      In experiment 1, water-holding capacity (WHC), insoluble dry matter, hydration
      rate, and FSG changes were determined in alfalfa hay (varying in particle size)
      and corn silage. Reduction of particle size increased bulk density, FSG, and the
      rate of hydration, and decreased WHC of alfalfa. In experiment 2, 9 midlactation
      Holstein dairy cows fed total mixed rations containing 3 sizes of alfalfa hay
      (with geometric mean 7.83, 4.04, and 1.14 mm) were used in a replicated 3 x 3
      Latin square design. The diets contained 20, 20, 35, 7, 7.5, 10, 0.3, 0.1, and
      0.1% of DM alfalfa, corn silage, barley, soybean meal, beet pulp, wheat bran,
      dicalcium phosphate, vitamin premix, and salt, respectively. The geometric means
      (GM) of rations were 3.34, 2.47, and 1.66 mm in long, medium, and fine alfalfa
      treatments, respectively. Reduction of particle size increased daily NDF intake
      (kg), but decreased the proportion of physically effective factor (pef) and
      physically effective NDF (peNDF) in the ingested rations. Reduction of particle
      size increased the FSG of rations and intake of DM but reduced digestibility of
      NDF and ash. Reduction of particle size decreased ruminal mean retention time
      (RMRT), but increased the ruminal particulate passage rate. Milk and FCM yield
      were not affected by treatments. The rumen pH, total chewing activity,
      rumination, eating time, and milk fat were reduced as particle size decreased,
      but milk protein increased. This study showed that reduction of forage particle
      size increased bulk density, FSG, and hydration rate of alfalfa and was the most
      influential factor affecting DMI, milk composition, and chewing behavior.
      Reduction of forage particle size had minimal impact on digestibility and milk
      production.

PMID- 15483176
TI  - Short communication: effect of leptin gene polymorphisms on breeding value for
      milk production traits.
AB  - New molecular techniques focused on genome analysis open new possibilities for
      complex evaluation of economically important traits in farm animals. Milk
      production traits are typical quantitative characteristics controlled by a number
      of genes. Mutations in their sequences may alter animal performance as well as
      their breeding values. In this study, we investigated the effect of 3 restriction
      fragment length polymorphisms (RFLP): HphI, Kpn2I, and Sau3AI in the leptin gene,
      on bull breeding values for milk, fat, and protein yield, and fat and protein
      content. One hundred seventeen Polish Black and White AI bulls were genotyped.
      Pedigree analysis indicated a relatively close relationship between the bulls.
      Statistical analysis indicated that the HphI polymorphism has a significant
      effect on milk and protein yield. Animals with the TT genotype had approximately
      2x higher estimated breeding values for milk and protein yields. No effect was
      found for the other 2 polymorphisms.

PMID- 15483177
TI  - Genetic variation in bovine mononuclear leukocyte responses to dexamethasone.
AB  - The objective of this study was to determine whether bovine mononuclear
      leukocytes exhibit genetic variability prior to and after a glucocorticoid
      hormone challenge in vivo. Test animals included 60 pedigreed Holstein bulls
      treated on 3 consecutive days with dexamethasone and 5 untreated control bulls.
      Eight indicator traits of leukocyte responsiveness to dexamethasone included the
      percentages of circulating B cells, T cells (CD4, CD8, and workshop cluster 1
      molecule expressed by bovine gammadelta T cell), major histocompatibility complex
      (MHC) I and II expressing cells, and mean expressions of surface MHC I and MHC II
      on circulating cells. Blood for this work was collected from each test bull 10
      times before, during, and after dexamethasone administration, with corresponding
      samples taken for control bulls. Random regression models with treatment-specific
      serial correlation were applied to the leukocyte data sets to estimate genetic
      and nongenetic sources of variation in baseline and recovery aspects of the
      traits. All traits responded predictably to glucocorticoid challenge. Genetic
      variation was observed in baseline measurements of all traits, with heritability
      estimates ranging from 0.21 +/- 0.03 to 0.60 +/- 0.06. Genetic variation in
      linear recovery from nadir values following dexamethasone administration was
      significant only for percentage CD4, percentage CD8, and for surface expression
      of MHC II. The genetic covariance between basal and linear recovery was positive
      and significant for percentage CD4, percentage CD8, and MHC II expression. The
      bovine lymphocyte antigen DRB3.2 locus accounted for significant proportions of
      total variation in percentage MHC II cells and MHC I expression. These results
      suggest that genetic variability exists for important basal and glucocorticoid
      modified phenotypes of bovine mononuclear leukocytes, implying that
      immunocompetence traits impacted by this stress hormone may be enhanced by
      genetic selection.

PMID- 15483178
TI  - Analysis of the relationship between type traits and functional survival in
      Canadian Holsteins using a Weibull proportional hazards model.
AB  - The aim of this study was to explore the impact of type traits on the functional
      survival of Canadian Holstein cows using a Weibull proportional hazards model.
      The data set consisted of 1,130,616 registered cows from 13,606 herds calving
      from 1985 to 2003. Functional survival was defined as the number of days from
      first calving to culling, death, or censoring. Type information consisted of
      phenotypic type scores for 8 composite traits (with 18 classes of each) and 23
      linear descriptive traits (with 9 classes of each). The statistical model
      included the effects of stage of lactation, season of production, the annual
      change in herd size, type of milk recording supervision, age at first calving,
      effects of milk, fat and protein yields calculated within herd-year-parity
      deviations, herd-year-season of calving, each type trait, and the sire. Analysis
      was done one at a time for each of 31 type traits. The relative culling risk was
      calculated for animals in each class after accounting for the previously
      mentioned effects. Among the composite type traits with the greatest contribution
      to the likelihood function were final score, mammary system, and feet and legs,
      all having a strong relationship with functional survival. Cows with low scores
      for these traits had higher risk of culling compared with higher scores. For
      instance, cows classified as poor plus 1 vs. excellent plus 1 have a relative
      risk of culling 3.66 and 0.28, respectively. The corresponding figures for
      mammary system are 4.19 and 0.46 and for feet and legs are 2.34 and 0.50. Linear
      type traits with the greatest contribution to the likelihood function were fore
      udder attachment, udder texture, udder depth, rear udder attachment height, and
      rear udder attachment width. Stature and size had no strong relationship with
      functional survival.

PMID- 15483179
TI  - Genetic analysis of male and female fertility using longitudinal binary data.
AB  - A longitudinal Bayesian threshold analysis of insemination events during the
      first 250 d after calving of first-parity Holsteins was carried out. The outcome
      of an insemination event was treated as a binary response of either a success (1)
      or a failure (0). Thus, all breeding information for a cow, including all service
      sires, was included, thereby allowing for a joint evaluation of male and female
      fertility. An edited data set of 297,823 insemination records from 151,758 first
      lactation cows was used. On the liability scale, the model included the
      systematic effects of herd-year of insemination, technician, month of
      insemination, and regressions on age of service sire, 3 test days in the first
      100 d of lactation (early milk yield), and days in milk at insemination. The
      random effects in the model were the additive breeding value, the permanent
      effect of the cow, and the service sire effect. Posterior mean (standard
      deviation) of the dispersion parameters in the model were 0.034 (0.006), 0.009
      (0.001), and 0.171 (0.013) for the additive, service sire, and permanent
      environmental variances, respectively. The residual variance was fixed at 1, as a
      result of the nonidentifiability of the threshold model. The posterior mean
      (standard deviation) of heritability was 0.028 (0.005). This point estimate of
      heritability is well within the range of available estimates for the trait. Thus,
      these estimates suggest that some genetic variation exists that can potentially
      be used to improve reproductive performance or at least avoid its further
      deterioration. The estimate of the regression coefficient on age of service sire
      was 0.001, indicating better fertility among older bulls. However, this result
      has to be interpreted with caution given the preferential use of proven bulls on
      well-managed cows (as opposed to problem breeders). The estimate of the
      regression coefficient was negative (-0.005) for early milk yield, as expected,
      and positive (0.003) for days in milk at insemination. This suggests that high
      producing cows are less likely to conceive at the beginning of lactation.

PMID- 15483180
TI  - Infrequent milk progesterone measurements in daughters enable bull selection for
      cow fertility.
AB  - The interval from calving to first luteal activity (CLA) has been suggested as an
      unbiased and, therefore, preferable measure for selection on female fertility in
      dairy cattle. However, measurement of this interval for individual cows is not
      feasible for reasons of cost and labor associated with the necessary frequent
      (milk) progesterone measurements. The objective of this study was to test the
      hypothesis that mean sire progesterone profiles based on individual progesterone
      measurements of daughters at 3- to 6-wk intervals have prospects as a measure for
      female fertility when selecting sires in a progeny testing scheme. In this study,
      progesterone concentrations were measured in milk samples collected at routinely
      performed milk recordings during the first 100 d of lactation of daughters of 20
      test bulls. It is demonstrated that a) mean progesterone profiles can be used to
      calculate the earliest stage of lactation at which at least 50% of the daughters
      of a test bull has a milk progesterone level >3 ng/mL (indicating luteal
      activity) and that b) this stage, at which 50% of the daughters of a bull have an
      active corpus luteum (CLA50%), varies largely between test bulls. We conclude
      that selecting sires based on daughter CLA50% may improve female fertility.

PMID- 15483181
TI  - Noncoagulation of milk in Finnish Ayrshire and Holstein-Friesian cows and effect
      of herds on milk coagulation ability.
AB  - The objectives of this study were to compare milk coagulation ability (MCA) and
      the prevalence of noncoagulation of milk within the main Finnish dairy breeds,
      Finnish Ayrshire (FA) and Holstein-Friesian (HOL), as well as to study the herd
      effect on MCA. Data used in the statistical analyses consisted of individual milk
      samples of 959 FA, 399 HOL, and 50 crossbred cows from 84 herds. Data were
      collected before the grazing season in the spring 1999. Milk samples were
      analyzed for the milk coagulation traits (milk renneting time, R and curd
      firmness, E(30)) and pH. In addition, information on the 305-d milk production
      traits from the year 1999, and background information about feeding and
      management regimes of the herds were obtained. Variance components for the random
      herd and animal effects were estimated using REML methodology and an animal
      model. Breed, parity, lactation stage (for R, E(30) and pH only), and a measuring
      unit (for R and E(30) only) were included as fixed effects in the model. When the
      effects of concentrate feeding frequency and type of concentrate were studied,
      the random effect of herd was excluded from the model. A relationship matrix
      included parents, grandparents, and great grandparents of the cows with
      observations. The HOL cows were superior to FA cows in MCA when both the
      proportion of poorly coagulating (PC) and noncoagulating (NC) milk, and the
      differences in curd firmness were considered. About 30% of the FA cows and 12% of
      the HOL cows produced PC milk. Only 1.3% of the HOL cows and 8.6% of the FA cows
      produced NC milk. Herd effect explained only a minor part of the variation in MCA
      (8%) compared with that in 305-d milk production traits (about 43%). Frequent
      feeding of the concentrate was associated with good MCA as well as for the high
      milk, protein and fat yields, but it was not associated with the prevalence of
      the NC milk.

PMID- 15483182
TI  - Genetic susceptibility to Neospora caninum infection in Holstein cattle in
      Ontario.
AB  - Neospora caninum has been reported to be an important cause of endemic fetal loss
      and occasional abortion epidemics in cattle around the world. This study examined
      12,016 sera collected from 9723 Holstein cows on 125 herds across Ontario in
      1998, 1999, and 2000. An enzyme-linked immunosorbent assay was used to examine
      the sera for antibodies to N. caninum. The overall prevalence of N. caninum
      antibodies in the cattle was 11.2% and the prevalence in individual herds varied
      from 0 to 70.4%. Among 3109 daughter-dam pairs, 619 positive dams had 252
      positive daughters, giving a detected vertical transmission rate of 40.7%. In
      contrast, there were only 6.7% positive daughters from negative dams (167 of
      2490). Pedigree edits left 8031 cows with 1463 sires for estimation of
      heritability. Five genetic models (sire model, animal model, sire-dam model, a
      sire-maternal grandsire model, and a maternal effects model) with fixed effects
      of bleeding year-month, age of the animals, and herd were fitted to the data. The
      estimated heritability of susceptibility to N. caninum ranged between 0.084 and
      0.124. The sire-maternal grandsire model and the maternal effects model provided
      better fit than the other models because the maternal genetic variance was much
      greater than the direct genetic variance. To reduce the incidence of N. caninum
      infection, more emphasis should be placed on management practices than on genetic
      selection.

PMID- 15483183
TI  - Deacidification by Debaryomyces hansenii of smear soft cheeses ripened under
      controlled conditions: relative humidity and temperature influences.
AB  - Model smear soft cheeses were prepared from pasteurized milk inoculated with
      Debaryomyces hansenii (304, GMPA) and Brevibacterium aurantiacum (ATCC 9175)
      under aseptic conditions. Debaryomyces hansenii growth and curd deacidification
      were studied in relation to ripening chamber temperature and relative humidity
      (RH). A total of 9 descriptors, mainly based on kinetic data, were defined to
      represent D. hansenii growth (2 descriptors), cheese deacidification (5
      descriptors), and cheese ripening (2 descriptors). Regardless of the temperature,
      when the RH was 85%, D. hansenii growth was inhibited due to limitation of carbon
      substrate diffusions; consequently, cheese deacidification did not take place.
      Debaryomyces hansenii growth was most prolific when the temperature was 16
      degrees C, and the RH was 95%. Kinetic descriptors of lactate consumption and pH
      increase were maximal at 16 degrees C and 100% RH. Under these 2 ripening
      conditions, on d 14 (packaging) the creamy underrind represented a third of the
      cheese; however, at the end of ripening (d 42), cheese was too liquid to be sold.
      Statistical analysis showed that the best ripening conditions to achieve an
      optimum between deacidification and appearance of cheeses (thickness of the
      creamy underrind) were 12 degrees C and 95 +/- 1% RH.

PMID- 15483184
TI  - Management practices from questionnaire surveys in herds with very low somatic
      cell score through a national mastitis program in France.
AB  - French dairy herds (n = 534) were enrolled in the National 'Zero Mastitis
      Objective' Program to highlight management practices characterizing very low
      somatic cell score (SCS) herds. The herds studied were stratified into 2 groups.
      The first group (LOW) included herds within the first 5 percentiles and the
      second group (MED) herds within the 50 to 55 percentiles of herds on the basis of
      mean SCS for the 36 mo preceding the program. Potential explanatory variables,
      collected through questionnaire surveys, were analyzed using multistep logistic
      regression models. Twenty-six variables were significant factors in the final
      models, in which 18 were considered as primary factors for very low SCS. The
      probability for a herd belonging to the LOW group was associated with: (1)
      regular use of teat spraying; (2) herdsman precise in his techniques; (3) less
      than 1 person-year used at activities other than dairy herd; (4) teat dipping
      after mammary infusion at dry off; (5) heifers kept in a calving pen around
      parturition; (6) cows locked in feed-line lockups after milking; (7) dry cows
      with prepartum Ca restriction; (8) heifers on a nondamp pasture; (9) cows culled
      when at least one damaged teat; (10) heifers at pasture not drinking water from a
      river; and (11) disinfecting teat ends with alcohol before intramammary infusion
      at dry off. The probability for a herd belonging to the MED group was associated
      with: (1) milking cows housed in a straw yard; (2) checking heifers for mastitis
      only beginning at 2-wk prepartum; (3) no mastitis treatment when at least one
      clot was observed in milk at successive milkings; (4) distance of herdsman's
      house to cowshed >300 m; (5) only dirty teats washed before milking; (6) free
      access of cows from pasture to cowshed during bad weather; and (7) more than 18%
      of spring calvings. The variables associated with very low SCS should be applied
      as part of a thorough mastitis-control program adapted to each herd.

PMID- 15483185
TI  - Aryl hydrocarbon receptor-activating polychlorinated biphenyls and their
      hydroxylated metabolites induce cell proliferation in contact-inhibited rat liver
      epithelial cells.
AB  - Polychlorinated biphenyls (PCBs) exhibit tumor-promoting effects in experimental
      animals. We investigated effects of six model PCB congeners and hydroxylated PCB
      metabolites on proliferation of contact-inhibited rat liver epithelial WB-F344
      cells. The 'dioxin-like' PCB congeners, PCB 126, PCB 105, and 4'-OH-PCB 79, a
      metabolite of the planar PCB 77 congener, induced cell proliferation in a
      concentration-dependent manner. In contrast, the 'non-dioxin-like' compounds that
      are not aryl hydrocarbon receptor (AhR) agonists, PCB 47, PCB 153, and 4-OH-PCB
      187, an abundant noncoplanar PCB metabolite, had no effect on cell proliferation
      at concentrations up to 10 muM. The concentrations of dioxin-like PCBs leading to
      cell proliferation corresponded with the levels inducing the expression of
      cytochrome P450 1A1 mRNA, suggesting that the release from contact inhibition was
      associated with AhR activation. The effects of PCB 126 and PCB 153 on expression
      of proteins controlling G0/G1-S-phase transition and S-phase progression were
      compared. Only PCB 126 was found to upregulate cyclin A and D2 protein levels,
      and to increase both total cyclin-dependent kinase 2 (cdk2) and cyclin A/cdk2
      complex activities. Despite the observed upregulation of cyclin D2, no increase
      in cdk4 activity was observed. The expression of cdk inhibitor p27Kip1 was not
      affected by either PCB 126 or PCB 153. These results suggest that dioxin-like
      PCBs can induce cell proliferation of contact-inhibited rat liver epithelial
      cells by increasing cyclin A protein levels, a process that then leads to
      upregulation of cyclin A/cdk2 activity and initiation of DNA replication. This
      mechanism could be involved in tumor-promoting effects of dioxin-like PCBs.

PMID- 15483186
TI  - Characterization of the N-methoxyindole-3-carbinol (NI3C)--induced cell cycle
      arrest in human colon cancer cell lines.
AB  - Recent results have shown that indole-3-carbinol (I3C) inhibits the cellular
      growth of human cancer cell lines. In some cruciferous vegetables, another
      indole, N-methoxyindole-3-carbinol (NI3C), is found beside I3C. Knowledge about
      the biological effects of NI3C is limited. The aim of the present study was to
      show the effect of NI3C on cell growth of two human colon cancer cell lines, DLD
      1 and HCT-116. For the first time it is shown that NI3C inhibits cellular growth
      of DLD-1 and HCT-116 and that NI3C is a more potent inhibitor of cell
      proliferation than I3C. In addition to the inhibition of cellular proliferation,
      NI3C caused an accumulation of HCT-116 cells in the G2/M phase, in contrast to
      I3C, which led to an accumulation of the colon cells in G0/G1 phase. Furthermore,
      NI3C delays the G1-S phase transition of synchronized HCT-116 cells. The indole
      mediated cell-cycle arrest may be related to the increased levels of the CDK
      inhibitors p21 and p27 (only induced by NI3C). Only an initial increase of cdc2
      protein was observed, whereas prolonged treatment with NI3C or I3C downregulates
      the mRNA and proteins of cyclin-dependent kinases and cyclins. These results
      indicate that both NI3C and I3C inhibit the proliferation of human colon cells
      but via different mechanisms.

PMID- 15483187
TI  - Inhaled diesel engine emissions reduce bacterial clearance and exacerbate lung
      disease to Pseudomonas aeruginosa infection in vivo.
AB  - Despite experimental evidence supporting an adverse role for air pollution in
      models of human disease, little has been done in the way of assessing the health
      effects of inhalation of whole mixtures from defined sources at exposure levels
      relevant to ambient environmental exposures. The current study assessed the
      impact of inhaled diesel engine emissions (DEE) in modulating clearance of
      Pseudomonas aeruginosa (P.a.) and the adverse effects of infection to the
      pulmonary epithelium. At DEE concentrations representing from high ambient to
      high occupational exposures, mice were exposed to DEE continuously for one week
      or six months (6 h/day), and subsequently infected with P.a. by intratracheal
      instillation. At 18 h following P.a. infection, prior exposure to DEE impaired
      bacterial clearance and exacerbated lung histopathology during infection. To
      assess the airway epithelial cell changes indicative of lung pathogenesis,
      markers of specific lung epithelial cell populations were analyzed by
      immunohistochemistry. Both ciliated and non-ciliated airway epithelial cell
      numbers were decreased during P.a. infection by DEE exposure in a concentration
      dependent manner. Furthermore, the lung transcription regulator, thyroid
      transcription factor 1 (TTF-1), was also decreased during P.a. infection by prior
      exposure to DEE concordant with changes in airway populations. These findings are
      consistent with the notion that environmental levels of DEE can decrease the
      clearance of P.a. and increase lung pathogenesis during pulmonary bacterial
      infection.

PMID- 15483188
TI  - Propylene oxide in blood and soluble nonprotein thiols in nasal mucosa and other
      tissues of male Fischer 344/N rats exposed to propylene oxide vapors--relevance
      of glutathione depletion for propylene oxide-induced rat nasal tumors.
AB  - High concentrations of propylene oxide (PO) induced inflammation in the
      respiratory nasal mucosa (RNM) of rodents. Concentrations > or =300 ppm caused
      nasal tumors. In order to investigate if glutathione depletion could be relevant
      for these effects, we determined in PO exposed male Fischer 344/N rats PO in
      blood and soluble nonprotein SH-groups (NPSH) in RNM and other tissues. Rats were
      exposed once (6 h) to PO concentrations between 0 and 750 ppm, and repeatedly for
      up to 20 days (6 h, 5 days/week) to concentrations between 0 and 500 ppm. At the
      end of the exposures, PO in blood and NPSH in tissues were determined. PO in
      blood was dependent on concentration and duration of exposure. After the 1-day
      exposures, NPSH depletion was most distinctive (RNM > liver > lung). Compared to
      controls, NPSH levels were 43% at 50 ppm PO in RNM and 16% at > or =300 ppm in
      both RNM and liver. Lung NPSH fell linearly to 20% at 750 ppm. After repeated
      exposures over 3 and 20 days to 5, 25, 50, 300, and 500 ppm, NPSH losses were
      less pronounced. At both time points, NPSH were 90%, 70%, 50%, 30%, and 30% of
      the control values in RNM. Liver NPSH decreased to 80% and 50% at 300 and 500
      ppm, respectively. After 20 days, lung NPSH declined to 70% (300 ppm) and 50%
      (500 ppm). We conclude that continuous, severe perturbation of GSH in RNM
      following repeated high PO exposures may lead to inflammatory lesions and cell
      proliferation, critical steps on the path towards tumorigenicity.

PMID- 15483189
TI  - Development of androgen- and estrogen-responsive bioassays, members of a panel of
      human cell line-based highly selective steroid-responsive bioassays.
AB  - We have established highly sensitive and specific androgen and estrogen reporter
      cell lines which we have named AR (androgen receptor) and ERalpha (estrogen
      receptor alpha) CALUX (Chemically Activated LUciferase eXpression), respectively.
      Both bioassays are member of a panel of CALUX reporter cell lines derived from
      the human U2-OS osteosarcoma cell line, all using highly selective reporter
      constructs based with a basal promoter element linked to multimerized response
      elements, allowing efficient and specific measurement of compounds interfering
      with androgen, estrogen, progesterone, and glucocorticoid receptors. The AR CALUX
      bioassay contains the human androgen receptor and a luciferase reporter construct
      containing three androgen-responsive elements coupled to a minimal TATA promoter.
      This cell line was characterized by its stable expression of AR protein, its
      highly selective response to low levels of different natural and synthetic
      androgens, and its insignificant response to other nuclear hormone receptor
      ligands such as estrogens, progestins, and glucocorticoids. The EC50 of
      dihydrotestosterone (DHT) was found to be 0.13 nM, consistent with the high
      affinity of this ligand to the human AR. Flutamide, cyproterone acetate, and the
      environmental contaminants vinclozolin, DDT, methoxychlor, its metabolite HPTE,
      and penta-BFR showed clear antagonistic activity in the AR CALUX bioassay,
      competitively inhibiting DHT-mediated transactivation. The established AR CALUX
      bioassay proved to excel in terms of easy cell line maintenance, high fold
      induction range (typical 30 times over solvent control), low minimal detection
      limit (3.6 pM), and high androgen selectivity. Potential applications such as
      testing the androgenic or estrogenic activity of pure chemicals and
      pharmaceuticals and complex mixtures (environmental, food, feed, and clinical)
      are discussed.

PMID- 15483190
TI  - A statistical evaluation of toxicity study designs for the estimation of the
      benchmark dose in continuous endpoints.
AB  - The benchmark approach is gaining attention as an alternative to the No-Observed
      Adverse-Effect-Level (NOAEL) approach. However, current guidelines for the design
      of toxicity tests are based on assessing a NOAEL. It has been suggested that the
      current study design may not be optimal for assessing a Benchmark Dose (BMD). To
      further investigate this we performed three simulation studies in which a large
      number of designs were compared, focusing on continuous endpoints. Four
      fictitious endpoints were considered, their underlying dose-response curves
      having a linear, sublinear, supralinear, or sigmoidal shape. In each simulation
      run the BMD was derived from a model fitted to the generated data, where the
      selection of the model was based on that particular data set (according to a
      formal likelihood ratio test procedure). Thus, the model used for deriving the
      BMD in a single generated data set may not be the same as the one used for
      generating the data. In this way, model uncertainty is taken into account as
      well. The results show that the performance of a design is, first of all,
      determined by the total number of animals used. Distributing them over more dose
      groups does not result in a poorer performance of the study, despite the smaller
      number of animals per dose group. Dose placement is another crucial factor, and
      to minimize the risk of inadequate dose placement, the use of multiple dose
      studies is favorable. As a concomitant advantage, the use of multiple doses
      mitigates the disturbing effect of potential systematic errors in single dose
      groups. However, for endpoints with large residual variation (CV > or = 18%)
      there is a substantial probability of not detecting the overall dose-response,
      and this probability increases in designs with increasing number of dose groups.
      In such situations, six dose groups may be used as a compromise. Designs with
      high dose levels (i.e., associated with relatively high effects) are helpful in
      estimating doses with smaller effects (such as the benchmark dose), and it
      appears bad practice to omit higher dose groups to improve the fit at lower
      doses. The typical 28-day study design of four dose groups with five animals (per
      sex) may not be adequate to assess endpoints with large residual variation (CV >
      or = 18%), both in assessing a benchmark dose and in assessing a NOAEL.

PMID- 15483191
TI  - Lipopolysaccharide-induced down-regulation of organic anion transporting
      polypeptide 4 (Oatp4; Slc21a10) is independent of tumor necrosis factor-alpha,
      Interleukin-1beta, interleukin-6, or inducible nitric oxide synthase.
AB  - Organic anion transporting polypeptide 4 (Oatp4; Slc21a10) is expressed almost
      exclusively in liver, where it mediates uptake of a variety of compounds,
      including bile acids, as well as other endo- and xenobiotics, across hepatic
      sinusoidal membranes in a Na+-independent manner. Lipopolysaccharide (LPS) has
      been shown to decrease Oatp4 mRNA levels in a dose- and time-dependent manner in
      Toll-like receptor 4 (TLR4)-normal (C3H/OuJ) mice, but not in TLR4-mutant
      (C3H/HeJ) mice. Moreover, after LPS administration, serum concentrations of tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin
      6 (IL-6) are markedly lower in TLR4-mutant mice than in TLR4-normal mice. Thus,
      TLR4 is considered an upstream mediator of LPS-induced decrease in mouse Oatp4
      mRNA. LPS is thought to alter liver gene expression through LPS-induced cytokines
      or nitric oxide (NO). TNF receptor p55 (TNFRp55) and type I IL-1 receptor (IL
      1RI) mediate the biological functions of TNF-alpha and IL-1beta, respectively.
      Therefore, to determine whether endogenous cytokines or NO are mediators of LPS
      induced down-regulation of Oatp4, Oatp4 mRNA levels were determined in mice
      deficient in the TNFRp55, IL-1RI, IL-6, or inducible nitric oxide synthase (iNOS)
      after LPS administration. Mice homozygous for a targeted deletion of genes for
      TNFRp55, IL-1RI, IL-6, or iNOS exhibited similar decreases in Oatp4 mRNA levels
      as wild-type mice after LPS administration. Moreover, in mouse hepatoma cells,
      treatment with TNF-alpha, IL-1beta, or IL-6 individually or in combination did
      not suppress activity of mouse Oatp4 promoter (-4.8 kb to +30). Therefore, LPS
      induced down-regulation of Oatp4 appears to be independent of TNF-alpha, IL
      1beta, IL-6, or iNOS.

PMID- 15483192
TI  - Structural analysis of CYP2C9 and CYP2C5 and an evaluation of commonly used
      molecular modeling techniques.
AB  - This work had two separate aims: to evaluate different modeling techniques and to
      make a detailed structural characterization of CYP2C9. To achieve these goals,
      the consensus principal component analysis (CPCA) technique and distance
      measurements were used to explore available crystal structures, newly built
      homology models, and repeated molecular dynamics simulations. The CPCA was based
      on molecular interaction fields focused on the active site regions of the
      proteins and include detailed amino acid analysis. The comparison of the CYP2C9
      and CYP2C5 crystal structures revealed differences in the flexible regions such
      as the B-C and F-G loop and the N and C termini. Cross homology models of CYP2C9
      and CYP2C5, using their respective crystal structures as templates, indicated
      that such models were more similar to their templates than to their target
      proteins. Inclusion of multiple templates slightly improved the similarity to the
      crystal target in some cases and could be recommended even though it requires a
      careful manual alignment process. The application of molecular dynamics
      simulations to highly flexible proteins such as cytochromes P450 is also explored
      and the information is extracted by the CPCA. Advantages and drawbacks are
      presented for the different modeling techniques. Despite the varying modeling
      success, the models give insight and understanding by the mutual forming and
      discarding of hypotheses. This is a dynamic process since the crystal structures
      are improving with time and, therefore, the answers to the models are also
      changing accordingly.

PMID- 15483193
TI  - Heterotropic modulation of sulfotransferase 2A1 activity by celecoxib: product
      ratio switching of ethynylestradiol sulfation.
AB  - The major sulfated product of 17alpha-ethynylestradiol (EE) after incubations
      with 3'-phosphoadenosine-5'-phosphosulfate and recombinant human sulfotransferase
      2A1 (SULT2A1), or liver cytosol, is the 3-O-sulfate of EE. However, when
      celecoxib is also present in the incubation, sulfation is switched (in a
      concentration-dependent manner) from the 3-O-position to the 17beta-O-position of
      ethynylestradiol. In incubations with recombinant SULT2A1, increasing
      concentrations of celecoxib decreased the Vmax of 3-O-sulfate product formation
      by 3- to 4-fold, with no major change in the Km value. For 17beta-O-sulfate
      formation, increasing concentrations of celecoxib resulted in an 8-fold decrease
      in the Km and a 7-fold increase in Vmax. Celecoxib not only modulated the
      regioselectivity of the enzyme, but also activated the enzyme such that total
      sulfated product exceeded product formation by the native enzyme, 3- to 4-fold
      (at 250 microM celecoxib). Finally, IC50 values obtained by varying celecoxib
      concentrations (0-250 microM) at fixed concentrations of EE showed that 3-O
      sulfation was inhibited by celecoxib to the same extent, independent of the
      concentration of EE. In addition, the apparent kinetic constant for celecoxib (as
      measured by EE 17beta-O-sulfation) decreased 2-fold in the presence of high
      concentrations of EE, consistent with the potential for celecoxib to bind to
      either the enzyme-EE complex or to free enzyme. Taken as a whole, these data
      suggest that celecoxib is acting as a heterotropic modulator of SULT2A1 activity,
      most likely involving a separate noncompetitive binding site.

PMID- 15483194
TI  - Down-regulation of mouse organic anion-transporting polypeptide 4 (Oatp4;
      Oatp1b2; Slc21a10) mRNA by lipopolysaccharide through the toll-like receptor 4
      (TLR4).
AB  - Lipopolysaccharide (LPS) causes a systemic reaction known as sepsis, which is
      frequently associated with cholestasis. Many biological effects produced by LPS
      are thought to be mediated by Toll-like receptor 4 (TLR4). Organic anion
      transporting polypeptide 4 (Oatp4; Slc21a10) mediates hepatic uptake of bile
      acids and other organic anions. The purpose of this study was to determine 1)
      whether LPS decreases Oatp4 mRNA levels; 2) the role of TLR4 in the LPS-induced
      down-regulation of Oatp4; and 3) the time course of serum concentrations of tumor
      necrosis factor alpha, interleukin (IL) 1beta, and IL-6 after LPS administration.
      For the dose-response study, LPS (1 mg/kg i.p.) produced a significant decrease
      in Oatp4 mRNA levels in TLR4-normal C3H/OuJ mice, and higher doses produced
      slightly greater decreases. However, none of the doses of LPS examined
      significantly decreased Oatp4 mRNA levels in TLR4-mutant C3H/HeJ mice. For the
      time-response study, LPS (5 mg/kg i.p.) produced a rapid decrease in Oatp4 mRNA
      levels in TLR4-normal C3H/OuJ mice. The maximal decrease in Oatp4 mRNA levels
      (80%) was observed 12 h after LPS administration and returned to control levels
      thereafter. In contrast, LPS did not produce a significant decrease in Oatp4 mRNA
      levels at any time in TLR4-mutant C3H/HeJ mice. These findings demonstrate that
      LPS decreases Oatp4 mRNA levels in mice, and the decrease is mediated through
      TLR4.

PMID- 15483195
TI  - In vitro characterization of clobazam metabolism by recombinant cytochrome P450
      enzymes: importance of CYP2C19.
AB  - The specific cytochrome P450 (P450) isoforms mediating the biotransformations of
      clobazam (CLB) and those of its major metabolites, N-desmethylclobazam (NCLB) and
      4'-hydroxyclobazam were identified using cDNA-expressed P450 and P450-specific
      chemical inhibitors. Among the 13 cDNA-expressed P450 isoforms tested, CLB was
      mainly demethylated by CYP3A4, CYP2C19, and CYP2B6 and 4'-hydroxylated by CYP2C19
      and CYP2C18. CYP2C19 and CYP2C18 catalyzed the 4'-hydroxylation of NCLB. The
      kinetics of the major biotransformations were studied: CYP3A4, CYP2C19, and
      CYP2B6 mediated the formation of NCLB with Km = 29.0, 31.9, and 289 microM, Vmax
      = 6.20, 1.15, and 5.70 nmol/min/nmol P450, and intrinsic clearance (CLint) = 214,
      36.1, and 19.7 microl/min/nmol P450, respectively. NCLB was hydroxylated to 4'
      hydroxydesmethylclobazam by CYP2C19 with Km = 5.74 microM, Vmax = 0.219
      nmol/min/nmol P450, and CLint = 38.2 microl/min/nmol P450 (Hill coefficient =
      1.54). These findings were supported by chemical inhibition studies in human
      liver microsomes. Indeed, ketoconazole (1 microM) inhibited the demethylation of
      CLB by 70% and omeprazole (10 microM) by 19%; omeprazole inhibited the
      hydroxylation of NCLB by 26%. Twenty-two epileptic patients treated with CLB were
      genotyped for CYP2C19. The NCLB/CLB plasma metabolic ratio was significantly
      higher in the subjects carrying one CYP2C19*2 mutated allele than in those
      carrying the wild-type genotype. CYP3A4 and CYP2C19 are the main P450s involved
      in clobazam metabolism. Interactions with other drugs metabolized by these P450s
      can occur; moreover, the CYP2C19 genetic polymorphism could be responsible for
      interindividual variations of plasma concentrations of N-desmethylclobazam and
      thus for occurrence of adverse events.

PMID- 15483196
TI  - Sulfotransferase 1E1 is a low km isoform mediating the 3-O-sulfation of ethinyl
      estradiol.
AB  - Sulfation of ethinyl estradiol (EE) is a major pathway of first pass metabolism
      in both the intestine and liver. Consequently, we sought to identify the human
      sulfotransferases (SULTs) involved in the 3-O-sulfation of EE (EE-SULT). Based on
      the results described herein, cDNA-expressed human cytosolic SULT1A3 and SULT1E1
      were identified as low Km isoforms (18.9 and 6.7 nM, respectively) mediating the
      sulfation of EE. In contrast, the EE-SULT catalyzed by other recombinant SULTs
      (SULT1A1 and 2A1) was a relatively high Km process (Km > or = 230 nM). The
      kinetics of EE-SULT in human intestine (Km1 = 24 nM; Km2 = 1206 nM) and liver
      (Km1 = 8 nM; Km2 = 2407 nM) cytosol was biphasic and conformed to a two-Km model
      with both low and high Km components. At a low EE concentration (3 nM),
      inhibition of EE-SULT activity (intestinal) was characterized with 2,6-dichloro p
      nitrophenol (DCNP) (IC50 = 15.6 microM) and quercetin (IC50 = 0.4 microM). When
      these IC50 values were compared with those derived from expressed enzyme,
      inhibition of EE-SULT was consistent with the SULT1E1 (DCNP, IC50 = 20 microM;
      quercetin, IC50 = 0.6 microM), but not SULT1A3 (DCNP, IC50 = 12.4; quercetin,
      IC50 = 7 microM). Moreover, when estrone (which selectively inhibits expressed
      SULT1E1 and SULT1A3) was included in intestinal incubations, the high-affinity
      component of the Eadie-Hofstee plot for EE sulfation was inhibited, converting
      the plot from biphasic to monophasic. Collectively, these data are consistent
      with SULT1E1 as the primary sulfotransferase involved in EE sulfation at
      clinically relevant concentrations (<10 nM).

PMID- 15483197
TI  - Valproyl-dephosphoCoA: a novel metabolite of valproate formed in vitro in rat
      liver mitochondria.
AB  - The mitochondrial metabolism of valproic acid (VPA) was investigated in vitro to
      elucidate its beta-oxidation pathway since the characterization of VPA
      intermediates in the acyl-CoA thioester form, and not just in their free acid
      form, has not been fully achieved. Intact rat liver mitochondria were incubated
      with [4,5-3H2]VPA and [2-3H]VPA. The respective intermediates, valproyl-CoA,
      Delta2(E)-valproyl-CoA, 3-hydroxyvalproyl-CoA, and 3-oxovalproyl-CoA were
      analyzed by reverse phase high performance liquid chromatography (HPLC) with
      radioisotope and UV detection. An unknown metabolite, originating from both
      labeled substrates, was detected. It was identified as valproyl-dephosphoCoA
      (valproyl-dephCoA) by fast atom bombardment mass spectrometry (FAB-MS) analysis
      of the corresponding HPLC peak fraction. The FAB-MS spectrum of the authentic
      chemically synthesized valproyl-dephCoA proved to be consistent with that of the
      unknown compound. Valproyl-dephCoA is produced from valproyl-CoA in mitochondria,
      probably via a phosphatase-catalyzed reaction. This conversion was shown to be
      more dependent on the energy state involving [AXP] ([AXP] = [ATP] + [ADP] +
      [AMP]) and [phosphate] concentrations rather than the strict mitochondrial
      [ATP]/[ADP] ratio. The results indicate that higher concentrations of AXP and
      phosphate inhibit the dephosphorylation of valproyl-CoA. A complete understanding
      of the toxic significance of valproyl-dephCoA formation in vivo as a potential
      inhibitor of fatty acid beta-oxidation is important to clarify the pathogenesis
      of VPA-associated hepatotoxicity.

PMID- 15483198
TI  - Hepatic microsome studies are insufficient to characterize in vivo hepatic
      metabolic clearance and metabolic drug-drug interactions: studies of digoxin
      metabolism in primary rat hepatocytes versus microsomes.
AB  - The effects of hepatic uptake and efflux transporters on metabolism of digoxin
      were examined in isolated rat hepatocytes versus microsomes. The metabolic
      clearance estimated from microsomes was 4.59 +/- 0.69 ml/min/kg. However, the
      metabolic clearance estimated from hepatocytes was 15.9 +/- 3.0 ml/min/kg. The
      former did not correlate with in vivo clearance (12.9 ml/min/kg) for digoxin.
      Rifampin (an organic anion-transporting peptide 2 inhibitor) or GG918 [GF120918
      (N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10
      dihydro-5-methoxy-9-oxo-4-acridine carboxamide)] (a potent P-glycoprotein
      inhibitor) were used to estimate effects of uptake or efflux transporters on
      digoxin metabolism. Whereas both inhibitors exerted minimal effects on metabolism
      in microsomes, rifampin and GG918 significantly decreased and increased digoxin
      metabolism in hepatocytes, respectively. Concentration-time course studies
      further demonstrated that, compared with the area under the curve (AUC) of
      control (15.6 +/- 0.1 microM . min), an increase of AUC (20.1 +/- 0.5 microM .
      min, p < 0.005) was observed when digoxin was coincubated with rifampin and a
      decrease of AUC (14.1 +/- 0.1 microM . min, p < 0.01) when GG918 was also
      present. Digoxin primary metabolite concentrations changed directionally in an
      inverse manner with parent drug concentrations, as would be expected. These
      results strongly suggest that the hepatic uptake and efflux transporters that are
      found in hepatocytes, but not in microsomes, modulate intracellular concentration
      of digoxin and thus affect metabolism. We conclude that the interplay of
      transporters and enzymes must be considered in defining the intrinsic metabolic
      clearance of the liver and in evaluating potential drug-drug interactions.

PMID- 15483199
TI  - Eating disorder or disordered eating? Non-normative eating patterns in obese
      individuals.
AB  - Binge eating disorder (BED) and night eating syndrome (NES) are putative eating
      disorders frequently seen in obese individuals. Data suggest that BED fulfills
      criteria for a mental disorder. Criteria for NES are evolving but at present do
      not require distress or functional impairment. It remains unclear whether BED and
      NES, as they are currently defined, are optimally useful for characterizing
      distinct patient subgroups. We propose that a distinction be made between "eating
      disorders" and "non-normative" eating patterns without associated distress or
      impairment. Although non-normative eating patterns may not be considered mental
      disorders, they may be very important in terms of their impact on body weight and
      health. More precise behavioral and metabolic characterization of subgroups with
      eating disorders and non-normative eating behaviors has important implications
      for understanding the etiology, pathophysiology, and treatment of obesity.
      Ultimately, better understanding of the many pathways to increased energy intake
      may lead to targeted strategies for prevention of overweight and obesity in at
      risk individuals and populations.

PMID- 15483200
TI  - Characteristics of men with persistent thinness.
AB  - OBJECTIVE: Although Western society is increasingly obesogenic, some individuals
      maintain low weights. Thin women manifest fewer eating disorders and higher self
      esteem. However, little is known about persistently thin men. RESEARCH METHODS
      AND PROCEDURES: Participants completed measures of demographics, psychiatric
      history, body size, eating behavior, and personality. RESULTS: Thinness was
      associated with less eating pathology. Thin men were more likely to meet criteria
      for generalized anxiety disorder (odds ratio = 2.46). DISCUSSION: Persistent
      thinness may protect men from eating disorders.

PMID- 15483201
TI  - Independent association of hip circumference with metabolic profile in different
      ethnic groups.
AB  - OBJECTIVE: In whites, a larger hip circumference has been shown to be associated
      with a better metabolic profile, after adjustment for BMI and waist
      circumference. Our aim was to investigate this association in a variety of ethnic
      groups, some highly susceptible to type 2 diabetes. RESEARCH METHODS AND
      PROCEDURES: We measured weight, height, waist and hip circumferences, systolic
      and diastolic blood pressure, fasting and 2-hour postload glucose, triglycerides,
      and high-density lipoprotein-cholesterol in 1020 Melanesians, 767 Micronesians,
      3697 Indians, and 2710 Creoles from Pacific and Indian Ocean islands. Leptin and
      body fat percentage were determined in Indian and Creole Mauritians only.
      RESULTS: In all ethnic groups, larger hip circumference was associated with lower
      glucose and triglyceride levels in both sexes and higher high-density lipoprotein
      levels in women only, after adjustment for waist circumference, BMI, and age.
      Adjustment for height or leptin did not materially change the results.
      DISCUSSION: In conclusion, we confirmed the protective association of relatively
      larger hips in four nonwhite ethnic groups. Leptin does not seem to play a
      mediating role in this association.

PMID- 15483202
TI  - Alcohol consumption and metabolic syndrome: does the type of beverage matter?
AB  - OBJECTIVE: To examine the association between total and beverage-specific alcohol
      consumption and the prevalence odds of metabolic syndrome (MS). RESEARCH METHODS
      AND PROCEDURES: Using a cross-sectional design, we studied 4510 white
      participants of the National Heart, Lung, and Blood Institute Family Heart Study.
      We used generalized estimating equations adjusting for age, education, risk
      group, smoking, physical activity, diabetes mellitus, coronary heart disease,
      energy intake, energy from fat, fruits, and vegetables, dietary cholesterol,
      dietary fiber, and use of multivitamins to estimate the prevalence odds of MS by
      alcohol intake. RESULTS: Compared with never-drinkers, multivariate odds ratios
      (95% confidence interval) for MS were 1.12 (0.85 to 1.49), 0.68 (0.36 to 1.28),
      0.72 (0.50 to 1.03), 0.66 (0.44 to 0.99), and 0.80 (0.55 to 1.16) among men who
      were former drinkers and who were current drinkers of 0.1 to 2.5, 2.6 to 12.0,
      12.1 to 24.0, and >24.0 g/d of alcohol, respectively (p for linear trend 0.018).
      Corresponding values for women were 0.86 (0.69 to 1.09), 0.80 (0.43 to 1.34),
      0.47 (0.33 to 0.66), 0.47 (0.30 to 0.74), and 0.39 (0.21 to 0.74), respectively
      (p for trend < 0.0001). The reduced prevalence odds of MS was observed across all
      beverage types: compared with never-drinkers, multivariate adjusted odds ratios
      (95% confidence interval) of MS were 0.32 (0.14 to 0.73), 0.42 (0.23 to 0.77),
      0.57 (0.30 to 1.09), and 0.56 (0.36 to 0.88) for subjects who consumed >7
      drinks/wk of wine only, beer only, spirits only, and more than one type of
      beverage, respectively. DISCUSSION: Our data indicate that alcohol consumption is
      associated with a lower prevalence of MS irrespective of the type of beverage
      consumed. Prospective studies are needed to confirm these findings and to assess
      the influence of drinking patterns on the alcohol-MS association.

PMID- 15483203
TI  - Alcohol intake and 8-year weight gain in women: a prospective study.
AB  - OBJECTIVE: To examine prospectively the relationship between alcohol and 8-year
      weight gain in women. RESEARCH METHODS AND PROCEDURES: A prospective study of
      49,324 women 27 to 44 years old who did not have a history of cardiovascular
      disease, cancer, or diabetes, who were not pregnant during the study period, and
      who reported weights in 1991 and 1999. RESULTS: In cross-sectional analyses,
      there was a significant inverse relationship between alcohol and BMI even after
      adjustment for dietary factors and a wide range of confounders. In multivariate
      prospective analyses, a nonlinear relationship was seen between alcohol and
      weight gain (>or=5 kg) in all women. Compared with nondrinkers, the adjusted
      relative odds [95% confidence interval (CI)] of weight gain according to grams
      per day were 0.94 (0.89, 0.99) for those consuming 0.1 to 4.9 g/d, 0.92
      (0.85,0.99) for 5 to 14.9 g/d, 0.86 (0.76, 0.78) for 15 to 29.9 g/d, and 1.07
      (0.89,1.28) for those consuming 30+ g/d (p < 0.0001 for quadratic trend). Women
      who continued to drink heavily and those who became heavy drinkers showed similar
      increased odds of weight gain. The increased odds of weight gain associated with
      heavy drinking (30+ g/d) were most marked in the younger women (<35 years) (odds
      ratio 1.64; 5% CI 1.03 to 2.61). In African-American women, light drinking was
      associated with increased odds of weight gain compared with nondrinkers (odds
      ratio = 2.43; 95% CI 1.22 to 4.82). DISCUSSION: Our data suggest that light to
      moderate drinking (up to 30 g/d) is not associated with weight gain in women
      except possibly in African-American women. Heavier drinking may promote weight
      gain in women.

PMID- 15483204
TI  - The M16 mouse: an outbred animal model of early onset polygenic obesity and
      diabesity.
AB  - OBJECTIVE: To characterize the phenotypic consequences of long-term selective
      breeding for rapid weight gain, with an emphasis on obesity and obesity-induced
      diabetes (diabesity). RESEARCH METHODS AND PROCEDURES: M16 is the result of long
      term selection for 3- to 6-week weight gain from an ICR base population.
      Experiment 1 characterized males from both lines for body weights (3, 6, and 8
      weeks), feed (4 to 8 weeks) and H(2)O (6 to 8 weeks) consumption, and heat loss,
      body composition, and levels of several plasma proteins at 8 weeks of age.
      Experiment 2 characterized differences between lines for both sexes at three ages
      (6, 8, and 16 weeks) and fed two diets (high and normal fat). Body weight,
      composition, blood glucose, and plasma insulin and leptin levels were evaluated
      after an 8-hour fast. RESULTS: At all ages measured, M16 mice were heavier,
      fatter, hyperphagic, hyperinsulinemic, and hyperleptinemic relative to ICR. M16
      males and females were hyperglycemic relative to ICR, with 56% and 22% higher
      fasted blood glucose levels at 8 weeks of age. DISCUSSION: M16 mice represent an
      outbred animal model to facilitate gene discovery and pathway regulation
      controlling early onset polygenic obesity and type 2 diabetic phenotypes.
      Phenotypes prevalent in the M16 model, with obesity and diabesity exhibited at a
      young age, closely mirror current trends in human populations.

PMID- 15483205
TI  - Characterization of QTL with major effects on fatness and growth on mouse
      chromosome 2.
AB  - OBJECTIVE: To isolate and characterize a region on mouse chromosome 2 harboring
      quantitative trait loci with large influences on growth and fatness. RESEARCH
      METHODS AND PROCEDURES: A congenic line [M16i.B6-(D2Mit306-D2Mit52); MB2] was
      created using the polygenic obese M16i selection line as the recipient for an
      approximately 38-centimorgan region from C57BL/6J. Males and females from M16i
      and MB2 were compared for body weight, body composition, feed consumption, and
      additional traits at 6, 15, and 24 weeks. Interactions of genotype and
      environment (low and high dietary fat) were investigated. Males (8 weeks) were
      evaluated for fatty acid profiles in liver and for transcriptional profiles in
      liver and adipose. RESULTS: Consequences of replacing M16i alleles with C57BL/6J
      alleles in MB2 were maximized at 15 weeks. MB2 mice were up to 15% lighter than
      M16i at this age, with no differences in feed consumption. As a percentage of
      body weight, MB2 had dramatically less epididymal (males) or perimetrial
      (females) fat (1.17% vs. 2.79% pooled across sex) and lower total lipids (16.1%
      vs. 23.3%) than M16i. Decreased adiposity in MB2 was not dependent on gender or
      diet. MB2 mice also had significant decreases in levels of leptin, insulin, and
      glucose, decreased de novo synthesis of hepatic fatty acid, and transcriptional
      changes for many genes both within, and external to, the congenic region.
      DISCUSSION: Results confirm the presence and large effects of mouse chromosome 2
      quantitative trait loci and further define their phenotypic consequences related
      to energy balance. The MB2 congenic line is a powerful resource for eventual
      identification of pathways and mutations within genes regulating predisposition
      to growth and obesity.

PMID- 15483206
TI  - Production rates of cortisol in obesity.
AB  - OBJECTIVE: To determine the metabolic clearance rates (MCRs) and endogenous
      production rates (PRs) of cortisol (F) in grades 2 and 3 obese men (n = 9) and
      women (n = 6). RESEARCH METHODS AND PROCEDURES: The MCRs and the endogenous PRs
      of cortisol (F) were determined in grades 2 and 3 obese men (n = 9) and women (n
      = 6) using the stable isotope dilution technique and mass spectrometry. RESULTS:
      In obese women, endogenous PRs of F (0.6 +/- 0.4 mg/h) were similar to those of
      nonobese women, but MCRs of F were higher in obese women (9 +/- 4 L/h) compared
      with nonobese women (5 + 2 L/h; p < 0.05). The MCR of F was correlated with the
      ratio of excreted cortisone to F metabolites. Furthermore, obese women were
      characterized by an increased ratio of androsterone to etiocholanolone (p <
      0.01). In obese men, the MCRs (11 +/- 6 L/h) and the endogenous PRs of F (0.6 +/-
      0.3 mg/h) were both similar to those of nonobese men, but the MCR of F was
      directly correlated with the ratio of excreted cortisone to F metabolites (r =
      0.7833, p = 0.012). DISCUSSION: These data demonstrate sex-specific differences
      in F metabolism in obesity. The rise in MCRs of F is more pronounced in obese
      women than in men. However, the increase in the MCR of F is moderate in both
      genders and exceeds the normal range only in a subgroup of obese individuals.

PMID- 15483207
TI  - Achieving weight and activity goals among diabetes prevention program lifestyle
      participants.
AB  - OBJECTIVE: The Diabetes Prevention Program (DPP) showed that intensive lifestyle
      intervention reduced the risk of diabetes by 58%. This paper examines
      demographic, psychosocial, and behavioral factors related to achieving weight
      loss and physical activity goals in the DPP lifestyle participants. RESEARCH
      METHODS AND PROCEDURES: Lifestyle participants (n = 1079; mean age = 50.6, BMI =
      33.9, 68% female, and 46% from minority groups) had goals of 7% weight loss and
      150 min/wk of physical activity. Goal achievement was assessed at the end of the
      16-session core curriculum (approximately week 24) and the final intervention
      visit (mean = 3.2 years) as a function of demographic, psychosocial, and
      behavioral variables. RESULTS: Forty-nine percent met the weight loss goal and
      74% met the activity goal initially, while 37% and 67%, respectively, met these
      goals long-term. Men and those with lower initial BMI were more likely to meet
      activity but not weight loss goals. Hispanic, Asian, and Native Americans were
      more likely to meet the long-term activity goals, and whites were more likely to
      meet the initial weight loss goal. In multivariate analyses, meeting the long
      term weight loss goal and both activity goals increased with age, while
      psychosocial and depression measures were unrelated to goal achievement. Dietary
      self-monitoring was positively related to meeting both weight loss and activity
      goals, and meeting the activity goal was positively related to meeting the weight
      loss goal. Participants who met initial goals were 1.5 to 3.0 times more likely
      to meet these goals long-term. DISCUSSION: Success at meeting the weight loss and
      activity goals increased with age. Initial success predicted long-term success.
      Self-monitoring and meeting activity goals were related to achieving and
      sustaining weight loss.

PMID- 15483208
TI  - Influence of dietary conjugated linoleic Acid and fat source on body fat and
      apoptosis in mice.
AB  - OBJECTIVE: To determine whether altered dietary essential fatty acid (linoleic
      and arachidonic acid) concentrations alter sensitivity to conjugated linoleic
      acid (CLA)-induced body fat loss or DNA fragmentation. RESEARCH METHODS AND
      PROCEDURES: Mice were fed diets containing soy oil (control), coconut oil
      [essential fatty acid deficient (EFAD)], or fish oil (FO) for 42 days, and then
      diets were supplemented with a mixture of CLA isomers (0.5% of the diet) for 14
      days. Body fat index, fat pad and liver weights, DNA fragmentation in adipose
      tissue, and fatty acid profiles of adipose tissue were determined. RESULTS: The
      EFAD diet decreased (p < 0.05) linoleic and arachidonic acid in mouse adipose
      tissue but did not affect body fat. Dietary CLA caused a reduction (p < 0.05) in
      body fat. Mice fed the EFAD diet and then supplemented with CLA exhibited a
      greater reduction (p < 0.001) in body fat (20.21% vs. 6.94% in EFAD and EFAD +
      CLA-fed mice, respectively) compared with mice fed soy oil. Dietary FO decreased
      linoleic acid and increased arachidonic acid in mouse adipose tissue. Mice fed FO
      or CLA were leaner (p < 0.05) than control mice. FO + CLA-fed mice did not differ
      in body fat compared with FO-fed mice. Adipose tissue apoptosis was increased (p
      < 0.001) in CLA-supplemented mice and was not affected by fat source. DISCUSSION:
      Reductions in linoleic acid concentration made mice more sensitive to CLA-induced
      body fat loss only when arachidonic acid concentrations were also reduced.
      Dietary essential fatty acids did not affect CLA-induced DNA fragmentation.

PMID- 15483209
TI  - Psychiatric and medical symptoms in binge eating in the absence of compensatory
      behaviors.
AB  - OBJECTIVE: To explore the extent to which binge eating in the absence of
      compensatory behaviors (BE) is associated with psychiatric and medical symptoms
      in men and women and to control for the independent effects of BMI. RESEARCH
      METHODS AND PROCEDURES: A series of regression models was applied to
      questionnaire data on 8045 twins, 18 to 31 years old, from a population-based
      Norwegian registry. RESULTS: BE was significantly associated with elevated
      obesity, overweight, symptoms of eating disorders, symptoms of anxiety and
      depression, panic attacks, depressive episodes, and reduced life satisfaction in
      both men and women. In women, BE was independently associated with insomnia and
      early menarche. In men, BE was independently associated with specific phobia,
      daily smoking, alcohol use, use of pain medication, impairment due to mental
      health, neck-shoulder, lower back, and chronic muscular pain, and impairment due
      to physical health. Both men and women with BE reported higher rates of
      psychiatric treatment. DISCUSSION: Our results indicate that there is substantial
      comorbidity between BE and psychiatric symptoms independently of BMI for both men
      and women. Medical symptoms co-occur less frequently than previously reported
      from treatment-seeking populations in women. Across all domains, the array of
      symptoms exhibited by men with BE was broader than that observed in women with
      BE. This observation suggests the importance of considering gender differences in
      future studies of psychiatric and medical morbidity, binge eating, and obesity.

PMID- 15483210
TI  - PPAR-gamma2 expression in response to cafeteria diet: gender- and depot-specific
      effects.
AB  - OBJECTIVE: To investigate the effects of short-term cafeteria (CAF) diet feeding
      on the expression of adipogenic transcription factors and their association with
      adiposity. RESEARCH METHODS AND PROCEDURES: Four-week-old male and female Wistar
      rats were fed CAF diet or standard chow for 2 weeks. Body weight, energy intake,
      tissue weights, and serum parameters were determined. Peroxisome proliferator
      activated receptor (PPAR)-gamma2, PPARalpha, CCAAT enhancer-binding protein
      alpha, and adipocyte differentiation and determination factor 1 mRNAs in gonadal
      white adipose tissue (gWAT) (visceral depot) and inguinal white adipose tissue
      (iWAT) (subcutaneous depot) and in interscapular brown adipose tissue were
      measured by reverse transcription-polymerase chain reaction. RESULTS: Short-term
      CAF diet feeding resulted in increases in body weight, adipose tissue weights,
      and lipid serum levels. Increased adiposity was more related to an increase in
      visceral fat than an increase in subcutaneous fat. This difference was associated
      with a higher expression of key adipogenic transcription factors (mainly
      PPARgamma2 and CCAAT enhancer-binding protein-alpha) in gWAT when compared with
      iWAT. Higher hypertrophy of gWAT was found in females, whereas males showed a
      higher hypertrophy of iWAT. Differential gender and depot response to CAF diet
      could be explained by depot and gender differential expression of key adipogenic
      transcription factors, especially PPARgamma2. Hence, reduced hypertrophy of
      female iWAT and defective thermogenesis in interscapular brown adipose tissue in
      response to CAF diet were related to decreased PPARgamma2 mRNA levels, whereas
      increased hypertrophy in male iWAT and gWAT and in female gWAT was related to a
      tendency toward increased PPARgamma2 mRNA levels in response to overfeeding.
      DISCUSSION: Our results suggest the involvement of PPARgamma2 in gender- and
      depot-specific effects of CAF diet on development and function in adipose
      tissues.

PMID- 15483211
TI  - Major increase in prevalence of overweight and obesity between 1987 and 2001
      among Danish adults.
AB  - OBJECTIVE: The aim of the study was to examine the secular trends in the
      prevalence of obesity (BMI >or= 30.0 kg/m(2)) and overweight (25.0 <or= BMI <
      30.0 kg/m(2)) in Danish adults between 1987 and 2001. RESEARCH METHODS AND
      PROCEDURES: The study included self-reported weight and height of 10,094 men and
      9897 women 16 to 98 years old, collected in a series of seven independent cross
      sectional surveys. Prevalence and changes in prevalence of obesity and overweight
      stratified by sex and age groups were determined. RESULTS: The prevalence of
      obesity more than doubled between 1987 and 2001, in men from 5.6% to 11.8% [odds
      ratio (OR) = 2.3, 95% confidence interval (CI) = 1.9 to 2.8, p < 0.0001] and in
      women from 5.4% to 12.5% (OR = 2.6, 95% CI = 2.1 to 3.2, p < 0.0001), with the
      largest increase among the 16- to 29-year-old subjects (men, from 0.8% to 7.5%,
      OR = 10.2, 95% CI = 4.1 to 25.3, p < 0.0001; women, from 1.4% to 9.0% OR = 7.0,
      95% CI = 3.5 to 14.1, p < 0.0001). Between 1987 and 2001, the prevalence of
      overweight increased from 34% to 40% in men and from 17% to 27% in women.
      DISCUSSION: The prevalence of overweight and obesity in Denmark has increased
      substantially between 1987 and 2001, particularly among young adults, a
      development that resembles that of other countries. There is clearly a need for
      early preventive efforts in childhood to limit the number of obesity-related
      complications in young adults.

PMID- 15483212
TI  - The relationship between body weight and health care among German women.
AB  - OBJECTIVE: To investigate the relationship between body weight and the use of
      health care services among women from southern Germany. RESEARCH METHODS AND
      PROCEDURES: Data were drawn from the 1994 to 1995 Monitoring of Trends and
      Determinants in Cardiovascular Disease Augsburg survey, covering a population
      representative sample of women 25 to 74 years old (n = 2301). Logistic regression
      models were used to calculate odds ratios (ORs) for the use of medical services
      by women with overweight (BMI 25.0 to 29.9 kg/m(2)) or obesity (BMI >or= 30
      kg/m(2)) in comparison with normal-weight women (BMI < 25.0 kg/m(2)). RESULTS: In
      multivariable analysis, obese women 50 to 74 years old were more likely than
      normal-weight women to delay cancer screening procedures, such as manual breast
      examination and Papanicolaou smear (OR 0.52, 95% confidence interval 0.37 to
      0.74) in the previous 12 months. However, the relationship between obesity and
      cancer screening was not found to be significant in 25- to 49-year-old women (OR
      0.92, 95% confidence interval 0.62 to 1.36). Neither in the 25- to 49-year-old
      age group nor in the 50- to 74-year-old age group were independent relationships
      between higher body weight and total physician visits, hospitalizations, or
      medication use observed. DISCUSSION: Obese women tended to use medical services
      with greater frequency due to obesity-related diseases. However, postmenopausal
      women with a BMI >or= 30 kg/m(2) were more likely to delay routine cancer
      screening, putting them at a greater risk for death from breast, cervical, and
      endometrial cancer. Thus, obese postmenopausal women should be targeted for
      increased screening.

PMID- 15483213
TI  - Sexual dimorphism and regulation of resistin, adiponectin, and leptin expression
      in the mouse.
AB  - OBJECTIVE: To examine gender differences and hormonal regulation of resistin,
      adiponectin, and leptin. RESEARCH METHODS AND PROCEDURES: Plasma levels were
      measured, and mRNA expression in perigonadal fat was quantified by RNase
      protection assays. RESULTS: Plasma resistin declined with age despite an increase
      in adiposity in both genders. In male mice, plasma leptin increased, whereas
      adiponectin levels were constant. In females, both adiponectin and leptin levels
      increased with age. Resistin mRNA levels were significantly higher in female than
      male mice at all ages, whereas leptin and adiponectin mRNA levels were similar in
      fat from 6-week-old male and female mice, and sexual dimorphism was apparent only
      in the older mice, with higher levels apparent in females. Castration did not
      abolish gender differences in plasma levels or resistin, adiponectin, or leptin
      mRNAs. Castration of male mice did not significantly change adipokine mRNA levels
      or plasma levels of resistin or leptin; however, adiponectin was significantly
      increased. Dihydrotestosterone treatment had no effect on adipokine mRNA
      expression or resistin and adiponectin levels but increased leptin levels. In
      contrast, ovariectomy significantly increased resistin mRNA abundance and
      decreased leptin and adiponectin mRNAs. Plasma leptin levels were also increased
      by ovariectomy, whereas resistin and adiponectin levels were unchanged. Estrogen
      replacement significantly reduced resistin mRNA and increased leptin and
      adiponectin mRNA levels but had no effect on plasma adipokine levels. DISCUSSION:
      The gender differences in adipokine mRNA expression and plasma levels were not
      ablated by castration and seem to be dependent on other factors in addition to
      gonadal steroids.

PMID- 15483214
TI  - Leptin and altitude in the cardiovascular diseases.
AB  - OBJECTIVE: The lower mortality from coronary ischemic disease in populations
      living at high altitude has been related to an increase of high-density
      lipoprotein (HDL)-cholesterol at altitude. Leptin has been proposed as a
      cardiovascular risk factor. We investigated whether leptin varies according to
      the altitude at which people live. RESEARCH METHODS AND PROCEDURES: This was a
      cross-sectional study of the first 889 people enrolled in a cohort study in the
      Canary Islands, Spain. The relationship among serum leptin, altitude, obesity,
      and other cardiovascular risk factors was analyzed by bivariate and multivariate
      tests. RESULTS: Leptin levels showed an inverse correlation to altitude expressed
      in meters (r = -0.10). Obese subjects had this leptin-altitude association (r = 
      0.19), but they also had a direct correlation of leptin to HDL-cholesterol (r =
      0.27) and an inverse correlation of leptin to the total cholesterol-to-HDL
      cholesterol ratio (r = -0.34), triglycerides (r = -0.29), apolipoprotein B (r = 
      0.21), and glycemia (r = -0.19). Nonobese subjects had only the leptin-altitude
      association (r = -0.11). The final regression model included altitude as
      predictor. Other associated variables were gender, physical activity, BMI, age,
      smoking (reducing leptin independently of BMI), alcohol, heart rate, and income.
      DISCUSSION: Serum leptin level decreases when altitude increases, and this
      association could help to explain the lower cardiovascular mortality rate at high
      altitude. However, because in obese subjects there is a direct association of
      leptin with HDL-cholesterol and an inverse association with the lipid atherogenic
      fractions, we suggest the hypothesis of different roles for bound and free
      leptin, with free leptin being a cardiovascular protective factor in obese
      people.

PMID- 15483215
TI  - Longitudinal relationship between elapsed time in the action stages of change and
      weight loss.
AB  - OBJECTIVE: The objective of this study was to examine the longitudinal
      relationship between the elapsed time in the action and maintenance stages of
      change for multiple target behaviors and weight loss or gain. RESEARCH METHODS
      AND PROCEDURES: The research design was a prospective cohort study of overweight
      and obese primary care patients randomized to an obesity management intervention
      based on the Transtheoretical Model and a chronic disease paradigm. The target
      behaviors included increased planned exercise and usual physical activity,
      decreased dietary fat, increased fruit and vegetable consumption, and increased
      dietary portion control. The participants were 329 middle-aged men and women with
      elevated body mass indices recruited from 15 primary care practices in
      Northeastern Ohio; 28% of the participants were African Americans. The main
      outcomes were weight loss (5% or more) or weight gain (5% or more) after 18 or 24
      months of follow-up. RESULTS: There were significant (p < 0.05) longitudinal
      relationships between the number of periods (0 to 4) in action or maintenance for
      each of the five target behaviors, or a composite score taken across the five
      target behaviors, and weight loss. In all cases, there was a significant (p <
      0.05) stepped (graded) relationship between the time in action or maintenance and
      weight loss (or gain). DISCUSSION: The data support the concept of applying the
      Transtheoretical Model to the problem of managing obesity in primary care
      settings. The remaining challenge is to identify those factors that reliably move
      patients into the action and maintenance stages for long periods.

PMID- 15483216
TI  - Gene or size: metabolic rate and body temperature in obese growth hormone
      deficient dwarf mice.
AB  - OBJECTIVE: SMA1 mice carry a missense mutation in the growth hormone gene that
      leads to semidominant dwarfism and obesity. In this study, the basic thermal and
      metabolic properties of SMA1 mice were examined to detect metabolic alterations
      that can support the accretion of excess fat. RESEARCH METHODS AND PROCEDURES:
      Basal and resting metabolic rates (RMRs) in wild-type and SMA1 (sma1/+ and
      sma1/sma1) mice were determined by indirect calorimetry. Body temperature (T(b))
      was recorded using intraperitoneally implanted temperature-sensitive
      transmitters, and body composition was determined by DXA. RESULTS: SMA1 mice have
      proportionally lower basal and resting metabolic rates, higher body mass (BM)
      specific RMRs, and a higher lower critical temperature, and display a decrease in
      T(b) by 0.4 degrees C in sma1/+ and 0.9 degrees C in sma1/sma1. DISCUSSION: The
      analysis of gene effects on BM and energy expenditure in mouse mutants must
      consider the appropriate allometric relationship between BM and metabolic rate.
      With the exception of T(b), all metabolic alterations observed in SMA1 reflect
      reduced size.

PMID- 15483217
TI  - The implications of body fat mass and fat distribution for cognitive function in
      elderly women.
AB  - OBJECTIVE: To investigate how body fat mass, an established source of endogenous
      estrogen after menopause, influences cognitive impairment in elderly women.
      RESEARCH METHODS AND PROCEDURES: Study participants were 5607 generally healthy
      postmenopausal women with mean age of 63.8 years at baseline followed for an
      average of 7.3 years. Cognitive function assessed at follow-up using the short
      Blessed test was related to baseline body weight, the yearly change in weight,
      and follow-up measures of body fat depots assessed by DXA. Cognitive function was
      also related to various surrogates of lifetime estrogen exposure. RESULTS: Women
      with the worst cognitive performance (score >or= 9) at follow-up were the ones
      who lost the most body weight and revealed the lowest central fat mass (CFM). The
      association of weight loss with worse cognitive performance was apparent across
      all age groups except for those more than 80 years old. In the multivariate
      logistic model, the risk of cognitive impairment was 18% lower in women in the
      second quartile of CFM (p = 0.14), 32% lower in the third (p = 0.01), and 48%
      lower in the fourth (p < 0.001) compared with those in the first quartile. CFM
      showed significant correlation with the simultaneously measured serum estradiol
      (r = 0.25; p < 0.001). Cognitive score showed an inverse linear relationship with
      the duration of reproductive period and bone mineral density assessed at follow
      up. DISCUSSION: These findings argue for a protective association of body fat
      mass with cognitive impairment in elderly women. This association seems to
      involve a more prominent exposure to endogenous estrogens.

PMID- 15483218
TI  - The effect of breast-feeding with and without formula use on the risk of obesity
      at 4 years of age.
AB  - OBJECTIVE: To determine the minimal duration of breast-feeding required to
      protect against later obesity, whether the concurrent use of formula lessened any
      protective effect of breast-feeding, and what maternal or child characteristics
      might modify the association between breast-feeding and child obesity. RESEARCH
      METHODS AND PROCEDURES: This was a retrospective cohort study. Participants were
      73,458 white and black low-income children followed from birth through 4 years of
      age. Obesity at age 4 years was defined as measured BMI >or= 95th percentile.
      Feeding exposure was based on breast-feeding duration and the age of formula
      initiation. Covariates were obtained from the children's birth certificates.
      RESULTS: At age 4 years, the prevalence of obesity was 11.5%. Only 16% of
      children were breast-fed 8 weeks or longer. Breast-feeding was associated with a
      reduced risk of obesity only in white children whose mothers had not smoked in
      pregnancy. In this subgroup, the reduction in obesity risk (adjusted odds ratio,
      95% confidence interval), compared with those never breast-fed, occurred only for
      children who were breast-fed at least 16 weeks without formula (0.71, 0.56 to
      0.92) or at least 26 weeks with concurrent formula (0.70, 0.61 to 0.81). Among
      whites whose mothers smoked in pregnancy and among blacks, breast-feeding was not
      associated with a reduced risk of obesity at age 4 years. DISCUSSION: In a
      population of low-income children, breast-feeding was associated with a reduced
      risk of obesity at age 4 years only among whites whose mothers did not smoke in
      pregnancy and only when breast-feeding continued for at least 16 weeks without
      formula or at least 26 weeks with formula.

PMID- 15483219
TI  - Other pathways to the manifestations of the metabolic syndrome in males.

PMID- 15483220
TI  - Recapitulation of the ovum mutant (Om) phenotype and loss of Om locus polarity in
      cloned mouse embryos.
AB  - The ovum mutant (Om) locus in mice affects early interactions between sperm and
      egg that in turn affect viability of embryos beyond the morula stage. Crosses of
      DDK females to males of many other inbred strains are 95% lethal around the
      morula stage, whereas reciprocal crosses are fully viable. Available data
      indicate that the early lethality is the result of an interaction between a
      factor in the ooplasm and the paternal genome. In this study, we examined whether
      this lethal interaction would likewise occur in cloned embryos produced by
      somatic cell nuclear transfer. We find that the Om effect is recapitulated but
      that the parental origin effect at the Om locus is no longer evident in cloned
      embryos.

PMID- 15483221
TI  - New preservation method for mouse spermatozoa without freezing.
AB  - The objective of this study was to investigate the preservation of spermatozoa in
      a simple medium without freezing and to examine the effects of the preserved
      sperm on fertilization and development after injection into mature mouse oocytes.
      Mouse spermatozoa were collected from two caudae epididymides of mature B6D2F1
      males and stored under various conditions: 1) in KSOMaa medium (potassium simplex
      optimized medium with amino acids) supplemented with 0, 1, or 4 mg/ml BSA and
      held at room temperature (RT, 27 degrees C); 2) in KSOMaa medium containing 4
      mg/ml BSA (KSOM-BSA) and held at 4 degrees C, RT, or 37 degrees C (CO2
      incubator); 3) in KSOM-BSA with osmolarity ranging from 271 to 2000 mOsmol,
      adjusted by addition of NaCl and held at 4 degrees C; and 4) a two-step
      preservation system consisting of storage in 800 mOsmol KSOM-BSA for 1 wk at RT
      followed by storage at -20 degrees C. Preservation of mouse spermatozoa at 4
      degrees C in a medium with high osmolarity (700-1000 mOsmol) resulted in the
      highest frequency of live births after intracytoplasmic sperm injection (ICSI)
      into mature oocytes. The optimal conditions for preservation of mouse spermatozoa
      were 800 mOsmol KSOM containing 4 mg/ml BSA and a holding temperature of 4
      degrees C. More than 40% of oocytes injected with sperm heads stored under these
      conditions for 2 mo developed to the morula/blastocyst stage in vitro and 39% of
      the embryos developed to term after transfer to recipient mice. Our results also
      indicate that mouse spermatozoa can be stored in 800 mOsmol KSOM-BSA medium at RT
      for 1 wk and then at -20 degrees C for up to 3 mo and retain their competence for
      ICSI. These new preservation methods permit extended conservation of viable
      spermatozoa that are capable of supporting normal embryonic development and the
      live birth of healthy offspring after ICSI.

PMID- 15483222
TI  - Effects of PNU157706, a dual 5alpha-reductase inhibitor, on rat epididymal sperm
      maturation and fertility.
AB  - Sperm entering the epididymis gain progressive motility and fertilizing ability
      in a process termed maturation. The functional dependence of the epididymis on
      dihydrotestosterone (DHT) is well established, yet few studies have examined the
      consequences on the epididymis of inhibiting DHT formation. We have shown that
      inhibition of both isoforms of 5alpha-reductase (types 1 and 2), the enzyme that
      converts testosterone to DHT, has pronounced effects on epididymal gene
      expression. In the present study, we investigate whether inhibiting 5alpha
      reductase has consequences on epididymal sperm maturation. Rats were treated with
      vehicle or 10 mg/kg/day PNU157706, a dual-type inhibitor, for 28 days. Fertility
      and several key facets of sperm maturation were analyzed. Changes in sperm
      motility were assessed by computer-assisted sperm analysis (CASA). Changes in
      sperm morphology were assessed by CASA and electron microscopy. The motility of
      spermatozoa from the cauda epididymidis of treated animals showed a significant
      decrease in both the percentage of motile and progressively motile sperm as well
      as altered motion parameters. The morphology of cauda epididymal spermatozoa was
      also adversely affected by the treatment; the most prominent effect was a
      markedly elevated proportion of sperm that retained their cytoplasmic droplet.
      Matings with treated males resulted in fewer successful pregnancies and a higher
      rate of preimplantation loss. Progeny outcome was unaffected. The compromised
      sperm motility and morphology likely contribute to the subfertility of inhibitor
      treated rats. Our results indicate a role for dual 5alpha-reductase inhibitors in
      further studies of epididymal physiology and as a potential component of a male
      contraceptive.

PMID- 15483223
TI  - Identification of differentially expressed genes in individual bovine
      preimplantation embryos produced by nuclear transfer: improper reprogramming of
      genes required for development.
AB  - Using an interwoven-loop experimental design in conjunction with highly
      conservative linear mixed model methodology using estimated variance components,
      18 genes differentially expressed between nuclear transfer (NT)- and in vitro
      fertilization (IVF)-produced embryos were identified. The set is comprised of
      three intermediate-filament protein genes (cytokeratin 8, cytokeratin 19, and
      vimentin), three metabolic genes (phosphoribosyl pyrophosphate synthetase 1,
      mitochondrial acetoacetyl-coenzyme A thiolase, and alpha-glucosidase), two
      lysosomal-related genes (prosaposin and lysosomal-associated membrane protein 2),
      and a gene associated with stress responses (heat shock protein 27) along with
      major histocompatibility complex class I, nidogen 2, a putative transport
      protein, heterogeneous nuclear ribonuclear protein K, mitochondrial 16S rRNA, and
      ES1 (a zebrafish orthologue of unknown function). The three remaining genes are
      novel. To our knowledge, this is the first report comparing individual embryos
      produced by NT and IVF using cDNA microarray technology for any species, and it
      uses a rigorous experimental design that emphasizes statistical significance to
      identify differentially expressed genes between NT and IVF embryos in cattle.

PMID- 15483224
TI  - Mechanisms of MAdCAM-1 gene expression in human intestinal microvascular
      endothelial cells.
AB  - Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is a homing receptor
      preferentially expressed on gut-associated endothelial cells that plays a central
      role in leukocyte traffic into the mucosal immune compartment. Although the
      molecular mechanisms underlying endothelial ICAM-1 or E-selectin expression have
      been intensively investigated, the mechanisms that regulate human MAdCAM-1
      expression have not been defined. We report MAdCAM-1 gene and protein expression
      in primary cultures of human intestinal microvascular endothelial cells (HIMEC)
      that was not demonstrated in human umbilical vein endothelial cells. Similar to
      ICAM-1 and E-selectin expression, MAdCAM-1 gene expression in HIMEC was inducible
      with TNF-alpha, IL-1beta, or LPS activation. However, in striking contrast to
      ICAM-1 and E-selectin expression, MAdCAM-1 mRNA and protein expression in HIMEC
      was heavily dependent on culture duration and/or cellular density, suggesting a
      prominent role for cell-cell interaction among these endothelial cells in the
      expression of the mucosal addressin. MAdCAM-1 expression was inhibited by both SN
      50 (NF-kappaB inhibitor) and LY-294002 [phosphatidylinositol 3-kinase (PI3-K)
      inhibitor], whereas ICAM-1 and E-selectin expression was inhibited by SN-50 but
      not by LY-294002. The Akt phosphorylation by TNF-alpha or LPS was greater at
      higher cell density, demonstrating a pattern similar to that of MAdCAM-1
      expression. NF-kappaB activation was not affected by cellular density in HIMEC.
      MAdCAM-1 expression in human gut endothelial cells is regulated by distinct
      signaling mechanisms involving both NF-kappaB and PI3-K/Akt. These data also
      suggest that PI3-K/Akt is involved in the gut-specific differentiation of HIMEC,
      which results in expression of the mucosal addressin MAdCAM-1.

PMID- 15483225
TI  - Static stretch promotes MEF2A nuclear translocation and expression of neonatal
      myosin heavy chain in C2C12 myocytes in a calcineurin- and p38-dependent manner.
AB  - Although the effects of mechanical stimuli have been studied extensively in fully
      differentiated skeletal muscle and have been shown to promote changes in
      phenotype, including altered myosin heavy chain isoform expression, the effects
      of a change in mechanical environment have been poorly studied at earlier stages
      of skeletal muscle differentiation. In particular, the early events elicited by
      mechanical stimuli upon differentiating myocytes have not been investigated. In
      the present study, the effect of static stretch on the activation of
      transcriptional factors MEF2A and NFATc1, which have been shown to be involved in
      the differentiation and phenotype regulation of skeletal muscle, have been
      examined. Furthermore, putative second messenger signaling pathways that could be
      involved in the dephosphorylation and hence activation of these factors were also
      examined. We have demonstrated that static stretch application produces a robust
      increase in p38 phosphorylation preceding MEF2A, but not NFATc1, nuclear
      translocation as well as deactivation of GSK-3beta via its phosphorylation. Using
      SB-203580 and cyclosporine A drugs to inhibit both p38- or/and calcineurin
      dependent signals, respectively, we have shown that MEF2A phosphorylation and
      subsequent nuclear translocation are regulated by p38 and calcineurin in a
      biphasic, time-dependent manner. Moreover, we also present evidence for another
      kinase that is involved in the stretch-related signal triggering MEF2A
      hyperphosphorylation, impairing its nuclear translocation, and that is related to
      p38. Finally, we have shown that static stretch application overnight promotes
      neonatal myosin heavy chain expression, which is inhibited by an inactivation of
      both p38 and calcineurin.

PMID- 15483226
TI  - Aging influences cellular and molecular responses of apoptosis to skeletal muscle
      unloading.
AB  - The influence of aging on skeletal myocyte apoptosis is not well understood. In
      this study we examined apoptosis and apoptotic regulatory factor responses to
      muscle atrophy induced via limb unloading following loading-induced hypertrophy.
      Muscle hypertrophy was induced by attaching a weight to one wing of young and
      aged Japanese quails for 14 days. Removing the weight for 7 or 14 days after the
      initial 14 days of loading induced muscle atrophy. The contralateral wing served
      as the intra-animal control. A time-released bromodeoxyuridine (BrdU) pellet was
      implanted subcutaneously with wing weighting to identify activated satellite
      cells/muscle precursor cells throughout the experimental period. Bcl-2 mRNA and
      protein levels decreased after 7 days of unloading, but they were unchanged after
      14 days of unloading in young muscles. Bcl-2 protein level but not mRNA level
      decreased after 7 days of unloading in muscles of aged birds. Seven days of
      unloading increased the mRNA level of Bax in muscles from both young and aged
      birds. Fourteen days of unloading increased mRNA and protein levels of Bcl-2,
      decreased protein levels of Bax, and decreased nuclear apoptosis-inducing factor
      (AIF) protein level in muscles of aged birds. BrdU-positive nuclei were found in
      all unloaded muscles from both age groups, but the number of BrdU-positive nuclei
      relative to the total nuclei decreased after 14 days of unloading compared with 7
      days of unloading. The TdT-mediated dUTP nick end labeling (TUNEL) index was
      higher after 7 days of unloading in both young and aged muscles and after 14 days
      of unloading in aged muscles. Immunofluorescent staining revealed that almost all
      of the TUNEL-positive nuclei were also BrdU immunopositive, suggesting that
      activated satellite cell nuclei (both fused and nonfused) underwent nuclear
      apoptosis during unloading. There were significant correlations among levels of
      Bcl-2, Bax, and AIF and TUNEL index. Our data are consistent with the hypothesis
      that apoptosis regulates, at least in part, unloading-induced muscle atrophy and
      loss of activated satellite cell nuclei in previously loaded muscles. Moreover,
      these data suggest that aging influences the apoptotic responses to prolonged
      unloading following hypertrophy in skeletal myocytes.

PMID- 15483227
TI  - Chemokine receptor CCR6 transduces signals that activate p130Cas and alter cAMP
      stimulated ion transport in human intestinal epithelial cells.
AB  - Human colon epithelial cells express the G protein-coupled receptor CCR6, the
      sole receptor for the chemokine CCL20 (also termed MIP-3alpha). CCL20 produced by
      intestinal epithelial cells is upregulated in response to proinflammatory stimuli
      and microbial infection, and it chemoattracts leukocytes, including CCR6
      expressing immature myeloid dendritic cells, into sites of inflammation. The aim
      of this study was to determine whether CCR6 expressed by intestinal epithelial
      cells acts as a functional receptor for CCL20 and whether stimulation with CCL20
      alters intestinal epithelial cell functions. The human colon epithelial cell
      lines T84, Caco-2, HT-29, and HCA-7 were used to model colonic epithelium.
      Polarized intestinal epithelial cells constitutively expressed CCR6,
      predominantly on the apical side. Consistent with this, apical stimulation of
      polarized intestinal epithelial cells resulted in tyrosine phosphorylation of the
      p130 Crk-associated substrate (Cas), an adaptor/scaffolding protein that
      localizes in focal adhesions and has a role in regulating cytoskeletal elements
      important for cell attachment and migration. In addition, CCL20 stimulation
      inhibited agonist-stimulated production of the second messenger cAMP and cAMP
      mediated chloride secretory responses by intestinal epithelial cells. Inhibition
      was abrogated by pertussis toxin, consistent with signaling through Galphai
      proteins that negatively regulate adenylyl cyclases and cAMP production. These
      data indicate that signaling events, occurring via the activation of the apically
      expressed chemokine receptor CCR6 on polarized intestinal epithelial cells, alter
      specialized intestinal epithelial cell functions, including electrogenic ion
      secretion and possibly epithelial cell adhesion and migration.

PMID- 15483228
TI  - Disruption of microtubular network attenuates histamine-induced dilation in rat
      mesenteric vessels.
AB  - Cytoplasmic microtubules are important in many cellular homeostatic processes in
      the cell. They regulate cell shape and movement as well as serving as a network
      by which vesicles and membrane-bound organelles can travel. Lately, there have
      been many studies demonstrating that microtubules are involved in regulation of
      intracellular signaling and, therefore, affect vascular reactivity. In this
      study, we tested the hypothesis that microtubule disruption attenuates agonist
      induced endothelium-dependent vasodilation. Isolated mesenteric arterial bed from
      normotensive rats was preconstricted with phenylephrine, and dose-response curves
      for histamine, acetylcholine (ACh), sodium nitroprusside (SNP), and pinacidil
      were performed before and after incubation with nocodazole or colchicine.
      Treatment of the vascular beds with nocodazole or colchicine significantly
      attenuated histamine relaxation but did not change the ACh-, SNP-, or pinacidil
      induced vasorelaxation. Nocodazole did not cause an additional attenuation of the
      histamine-mediated dilation in mesenteric vessels in the presence of Nomega-nitro
      L-arginine methyl ester, high extracellular K+, or K+ channel blockers. These
      data suggest that disruption of microtubules affects an essential endothelial
      component of histamine-mediated vasodilation in the mesenteric arterial bed. The
      mechanism(s) involved in this effect might be related to an impairment of
      endothelial NO synthesis, which might not be as important for the ACh as for the
      histamine vasodilator response in rat mesenteric vessels. These results
      demonstrate the importance of the microtubular system for endothelium-dependent
      NO-mediated smooth muscle relaxation.

PMID- 15483229
TI  - Multiple pathways for cationic amino acid transport in rat thyroid epithelial
      cell line PC Cl3.
AB  - Information regarding cationic amino acid transport systems in thyroid is limited
      to Northern blot detection of y(+)LAT1 mRNA in the mouse. This study investigated
      cationic amino acid transport in PC cell line clone 3 (PC Cl3 cells), a thyroid
      follicular cell line derived from a normal Fisher rat retaining many features of
      normal differentiated follicular thyroid cells. We provide evidence that in PC
      Cl3 cells plasmalemmal transport of cationic amino acids is Na+ independent and
      occurs, besides diffusion, with the contribution of high-affinity, carrier
      mediated processes. Carrier-mediated transport is via y+, y(+)L, and b(0,+)
      systems, as assessed by L-arginine uptake and kinetics, inhibition of L-arginine
      transport by N-ethylmaleimide and neutral amino acids, and L-cystine transport
      studies. y(+)L and y(+) systems account for the highest transport rate (with
      y(+)L > y+) and b(0,+) for a residual fraction of the transport. Uptake data
      correlate to expression of the genes encoding for CAT-1, CAT-2B, 4F2hc, y(+)LAT1,
      y(+)LAT2, rBAT, and b(0,+)AT, an expression profile that is also shown by the rat
      thyroid gland. In PC Cl3 cells cationic amino acid uptake is under TSH and/or
      cAMP control (with transport increasing with increasing TSH concentration), and
      upregulation of CAT-1, CAT-2B, 4F2hc/y(+)LAT1, and rBAT/b(0,+)AT occurs at the
      mRNA level under TSH stimulation. Our results provide the first description of an
      expression pattern of cationic amino acid transport systems in thyroid cells.
      Furthermore, we provide evidence that extracellular L-arginine is a crucial
      requirement for normal PC Cl3 cell growth and that long-term L-arginine
      deprivation negatively influences CAT-2B expression, as it correlates to
      reduction of CAT-2B mRNA levels.

PMID- 15483230
TI  - Genetic diversity and evolution of hepatitis C virus--15 years on.
AB  - In the 15 years since the discovery of hepatitis C virus (HCV), much has been
      learned about its role as a major causative agent of human liver disease and its
      ability to persist in the face of host-cell defences and the immune system. This
      review describes what is known about the diversity of HCV, the current
      classification of HCV genotypes within the family Flaviviridae and how this
      genetic diversity contributes to its pathogenesis. On one hand, diversification
      of HCV has been constrained by its intimate adaptation to its host. Despite the
      >30 % nucleotide sequence divergence between genotypes, HCV variants nevertheless
      remain remarkably similar in their transmission dynamics, persistence and disease
      development. Nowhere is this more evident than in the evolutionary conservation
      of numerous evasion methods to counteract the cell's innate antiviral defence
      pathways; this series of highly complex virus-host interactions may represent key
      components in establishing its 'ecological niche' in the human liver. On the
      other hand, the mutability and large population size of HCV enables it to respond
      very rapidly to new selection pressures, manifested by immune-driven changes in T
      and B-cell epitopes that are encountered on transmission between individuals
      with different antigen-recognition repertoires. If human immunodeficiency virus
      type 1 is a precedent, future therapies that target virus protease or polymerase
      enzymes may also select very rapidly for antiviral-resistant mutants. These
      contrasting aspects of conservatism and adaptability provide a fascinating
      paradigm in which to explore the complex selection pressures that underlie the
      evolution of HCV and other persistent viruses.

PMID- 15483231
TI  - Evidence for hepatitis E virus quasispecies.
AB  - The genetic diversity of hepatitis E virus (HEV) has been extensively analysed
      during the last decade. Most sporadic and epidemic HEV strains are distributed
      into genotypes or groups. Nevertheless, few studies have looked at the
      polymorphism of HEV strains isolated from a given outbreak. A serum bank
      collected in Tanefdour, Algeria, during an acute hepatitis epidemic (1986-1987),
      retrospectively confirmed as hepatitis E, was analysed. Of the 69 serum samples
      collected within an 8-week period, 23 were positive for both partial ORF1
      (replicase gene) and ORF2 (capsid gene) sequences. Inter- and intra-patient
      diversities were assessed by RFLP, and by sequencing a 448 bp sequence
      corresponding to ORF2. RFLP analysis distinguished three profiles: A (18/23), B
      (3/23) and C (2/23). Most isolates (18/23) shared 99.7-100 % sequence identity
      and the remainder showed 1-1.3 % divergence. HEV intra-patient diversity was
      studied using 12 isolates (seven displaying the major RFLP profile and five
      displaying minor RFLP profiles). For 9 of 12 isolates, additional intra-patient
      heterogeneity was revealed by RFLP analysis of 100 clones from each isolate and
      sequence diversity ranging from 0.11 to 3.4 %. These data strongly support the
      quasispecies organization of HEV during epidemics and could explain the adaptable
      behaviour of the virus in the host-pathogen interrelations.

PMID- 15483232
TI  - Bovine enterovirus 2: complete genomic sequence and molecular modelling of a
      reference strain and a wild-type isolate from endemically infected US cattle.
AB  - Bovine enteroviruses are members of the family Picornaviridae, genus Enterovirus.
      Whilst little is known about their pathogenic potential, they are apparently
      endemic in some cattle and cattle environments. Only one of the two current
      serotypes has been sequenced completely. In this report, the entire genome
      sequences of bovine enterovirus 2 (BEV-2) strain PS87 and a recent isolate from
      an endemically infected herd in Maryland, USA (Wye3A) are presented. The recent
      isolate clearly segregated phylogenetically with sequences representing the BEV-2
      serotype, as did other isolates from the endemic herd. The Wye3A isolate shared
      82 % nucleotide sequence identity with the PS87 strain and 68 % identity with a
      BEV-1 strain (VG5-27). Comparison of BEV-2 and BEV-1 deduced protein sequences
      revealed 72-73 % identity and showed that most differences were single amino acid
      changes or single deletions, with the exception of the VP1 protein, where both
      BEV-2 sequences were 7 aa shorter than that of BEV-1. Homology modelling of the
      capsid proteins of BEV-2 against protein database entries for picornaviruses
      indicated six significant differences among bovine enteroviruses and other
      members of the family Picornaviridae. Five of these were on the 'rim' of the
      proposed enterovirus receptor-binding site or 'canyon' (VP1) and one was near the
      base of the canyon (VP3). Two of these regions varied enough to distinguish BEV-2
      from BEV-1 strains. This is the first report and analysis of full-length
      sequences for BEV-2. Continued analysis of these wild-type strains should yield
      useful information for genotyping enteroviruses and modelling enterovirus capsid
      structure.

PMID- 15483234
TI  - Inhibition of foot-and-mouth disease virus replication by small interfering RNA.
AB  - Foot-and-mouth disease, caused by foot-and-mouth disease virus (FMDV), is one of
      the most dangerous diseases of cloven-hoofed animals and is a constant threat to
      the dairy and beef industries in the Middle East and other regions of the world,
      despite intensive vaccination programmes. In this work, the ability of specific
      small interfering (si)RNAs to inhibit virus replication in BHK-21 cells was
      examined. By using bioinformatic computer programs, all FMDV sequences in public
      domain databases were analysed. The analysis revealed three regions of at least
      22 bp with 100 % identity in all FMDV entries. From these sequences, three
      specific siRNA molecules were prepared and used to test the ability of siRNAs to
      inhibit virus replication. By using real-time quantitative PCR to measure the
      amount of viral RNA in infected cells, it was shown that virus replication was
      inhibited in cells that were transfected with siRNAs. When viral titres were
      examined, 100 % inhibition of growth could be demonstrated in cells transfected
      with a mixture of all three anti-FMDV siRNAs, compared with control cells
      transfected with anti-LacZ siRNA.

PMID- 15483233
TI  - Molecular identification and characterization of two proposed new enterovirus
      serotypes, EV74 and EV75.
AB  - Sequencing of the gene that encodes the capsid protein VP1 has been used as a
      surrogate for antigenic typing in order to distinguish enterovirus serotypes;
      three new serotypes were identified recently by this method. In this study, 14
      enterovirus isolates from six countries were characterized as members of two new
      types within the species Human enterovirus B, based on sequencing of the complete
      capsid-encoding (P1) region. Isolates within each of these two types differed
      significantly from one another and from all other known enterovirus serotypes on
      the basis of sequences that encode either VP1 alone or the entire P1 region.
      Members of each type were > or =77.2 % identical to one another (89.5 % amino
      acid identity) in VP1, but members of the two different types differed from one
      another and from other enteroviruses by > or =31 % in nucleotide sequence (25 %
      amino acid sequence difference), indicating that the two groups represent
      separate new candidate enterovirus types. The complete P1 sequences differed from
      those of all other enterovirus serotypes by > or =31 % (26 % amino acid sequence
      difference), but were highly conserved within a serotype (<8 % amino acid
      sequence difference). Phylogenetic analyses demonstrated that isolates of the
      same serotype were monophyletic in both VP1 and the capsid as a whole, as shown
      previously for other enterovirus serotypes. This paper proposes that these 14
      isolates should be classified as members of two new human enterovirus types,
      enteroviruses 74 and 75 (EV74 and EV75).

PMID- 15483235
TI  - Development of a reverse-genetics system for Avian pneumovirus demonstrates that
      the small hydrophobic (SH) and attachment (G) genes are not essential for virus
      viability.
AB  - Avian pneumovirus (APV) is a member of the genus Metapneumovirus of the subfamily
      Pneumovirinae. This study describes the development of a reverse-genetics system
      for APV. A minigenome system was used to optimize the expression of the
      nucleoprotein, phosphoprotein, M2 and large polymerase proteins when transfected
      into Vero cells under the control of the bacteriophage T7 promoter. Subsequently,
      cDNA was transcribed from the virion RNA to make a full-length antigenome, which
      was also cloned under the control of the T7 promoter. Transfection of the full
      length genome plasmid, together with the plasmids expressing the functional
      proteins in the transcription and replication complex, generated APV in the
      transfected cells. The recombinant virus was passaged and was identified by
      cytopathic effect (CPE) that was typical of APV, the presence of a unique
      restriction-endonuclease site in the cDNA copy of the genome and
      immunofluorescence staining with anti-APV antibodies. Replacement of the full
      length wild-type antigenome with one lacking the small hydrophobic (SH) protein
      and the attachment (G) genes generated a virus that grew more slowly and produced
      atypical CPE with syncytia much larger than those seen with wild-type virus.

PMID- 15483236
TI  - Shifting immunodominance pattern of two cytotoxic T-lymphocyte epitopes in the F
      glycoprotein of the Long strain of respiratory syncytial virus.
AB  - Human respiratory syncytial virus (RSV) is a major cause of respiratory infection
      in children and in the elderly. The RSV fusion (F) glycoprotein has long been
      recognized as a vaccine candidate as it elicits cytotoxic T-lymphocyte (CTL) and
      antibody responses. Two murine H-2K(d)-restricted CTL epitopes (F85-93 and F92
      106) are known in the F protein of the A2 strain of RSV. F-specific CTL lines
      using BCH4 fibroblasts that are persistently infected with the Long strain of
      human RSV as stimulators were generated, and it was found that in this strain
      only the F85-93 epitope is conserved. Motif based epitope prediction programs and
      an F2 chain deleted F protein encoded in a recombinant vaccinia virus enabled
      identification of a new epitope in the Long strain, F249-258, which is presented
      by K(d) as a 9-mer (TYMLTNSEL) or a 10-mer (TYMLTNSELL) peptide. The results
      suggest that the 10-mer might be a naturally processed endogenous K(d) ligand.
      The CD8(+) T-lymphocyte responses to epitopes F85-93 and F249-258 present in the
      F protein of RSV Long were found to be strongly skewed to F85-93 in in vitro
      multispecific CTL lines and in vivo during a secondary response to a recombinant
      vaccinia virus that expresses the entire F protein. However, no hierarchy in
      CD8(+) T-lymphocyte responses to F85-93 and F249-258 epitopes was observed in
      vivo during a primary response.

PMID- 15483237
TI  - Impact of measles virus dendritic-cell infection on Th-cell polarization in
      vitro.
AB  - Interference of measles virus (MV) with dendritic-cell (DC) functions and
      deregulation of T-cell differentiation have been proposed to be central to the
      profound suppression of immune responses to secondary infections up to several
      weeks after the acute disease. To address the impact of MV infection on the
      ability of DCs to promote Th-cell differentiation, an in vitro system was used
      where uninfected, tumour necrosis factor alpha/interleukin (IL) 1 beta-primed DCs
      were co-cultured with CD45RO(-) T cells in the presence of conditioned media from
      MV-infected DCs primed under neutral or DC-polarizing conditions. It was found
      that supernatants of DCs infected with an MV vaccine strain strongly promoted Th1
      differentation, whereas those obtained from wild-type MV-infected DCs generated a
      mixed Th1/Th0 response, irrespective of the conditions used for DC priming. Th
      cell commitment in this system did not correlate with the production of IL12 p70,
      IL18 or IL23. Thus, a combination of these or other, as yet undefined, soluble
      factors is produced upon MV infection of DCs that strongly promotes Th1/Th0
      differentiation.

PMID- 15483238
TI  - Homology model of the structure of influenza B virus HA1.
AB  - Influenza B virus is one of two types of influenza virus that cause substantial
      morbidity and mortality in humans, the other being influenza A virus. The
      inability to provide lasting protection to humans against influenza B virus
      infection is due, in part, to antigenic drift of the viral surface glycoprotein,
      haemagglutinin (HA). Studies of the antigenicity of the HA of influenza B virus
      have been hampered by lack of knowledge of its structure. To address this gap,
      two possible models have been inferred for this structure, based on two known
      structures of the homologous HA of the influenza A virus (subtypes H3 and H9).
      Statistical, structural and functional analyses of these models suggested that
      they matched important details of experimental observations and did not differ
      from each other in any substantive way. These models were used to investigate two
      HA sites at which viral variants appeared to carry a selective advantage. It was
      found that each of these sites coevolved with nearby sites to compensate for
      either size or charge changes.

PMID- 15483239
TI  - Tula hantavirus infection of Vero E6 cells induces apoptosis involving caspase 8
      activation.
AB  - Hantaviruses are known to cause two severe human diseases: haemorrhagic fever
      with renal syndrome and hantavirus pulmonary syndrome. The mechanisms of
      pathogenesis of these two diseases are progressively becoming understood.
      Recently, two hantaviruses, Hantaan and Prospect Hill were reported to cause
      programmed cell death of Vero E6 cells. This study shows that Tula hantavirus
      (TULV) infection efficiently triggers an apoptotic programme in infected Vero E6
      cells, and that the replication of TULV is required for the activation of caspase
      3 and the cleavage of poly (ADP-ribose) polymerase, two molecular hallmarks of
      apoptosis. The enforced treatment of infected Vero E6 cells with tumour necrosis
      factor alpha (TNF-alpha), but not interferon alpha (IFN-alpha), advanced the time
      course of apoptosis. Furthermore, caspase 8 was activated on day 4 post
      infection, the same day when caspase 3 was activated. TNF receptor 1 was induced
      during a late stage of TULV infection. These data suggest that, unlike during
      influenza A virus infection, TNF-alpha, but not type I IFN-alpha/beta, may
      contribute significantly to apoptosis in a synergistic manner with TULV
      propagation. Interestingly, pretreatment with a broad-spectrum caspase inhibitor,
      z-VAD-fmk, efficiently inhibited apoptosis of TULV-infected Vero E6 cells. Taken
      together, these results suggest that TULV replication initiates a typical
      apoptotic programme involving caspase 8 activation.

PMID- 15483240
TI  - Complementarity, sequence and structural elements within the 3' and 5' non-coding
      regions of the Bunyamwera orthobunyavirus S segment determine promoter strength.
AB  - The genome of Bunyamwera virus (BUN; family Bunyaviridae) consists of three
      segments of negative-sense, single-stranded RNA that are called L (large), M
      (medium) and S (small), according to their size. The genomic RNAs are
      encapsidated by the viral nucleocapsid protein to form ribonucleoprotein
      complexes (RNPs). The terminal 3' and 5' non-coding sequences are complementary
      and interact to give a panhandle-like structure to the RNP. Located within these
      non-coding sequences are elements that control replication and transcription. The
      sequences of the terminal 11 nt are conserved among the genome segments and are
      followed by shorter, complementary nucleotide motifs that are conserved on a
      segment-specific basis. Here, a detailed analysis of the 3' and 5' non-coding
      regions of the BUN S segment is presented. By using a mini-replicon system, it
      was shown that a functional BUN S promoter requires complementarity, as well as
      defined sequences, within the terminal 15 nt of either end. It was also shown
      that the minimal requirement for transcription is localized within the terminal
      32 nt of the S segment. A comparison of known strong BUN promoters led to the
      prediction of a structural element outside the terminal 15 nt; introduction of
      this motif into the BUN S sequence resulted in increased antigenome and mRNA
      levels and increased expression of S segment proteins, as shown by mini-replicon
      assays, as well as recovery of a recombinant virus.

PMID- 15483241
TI  - Identification of a conserved linear epitope at the N terminus of the rabies
      virus glycoprotein.
AB  - A novel, linear B-cell epitope has been identified at the N terminus of the
      rabies virus (RABV) glycoprotein. Screening of a phage-display library
      demonstrated that two glycoprotein-specific mAbs recognized a conserved sequence,
      WxxxDI, which aligned between aa 14 and 19 of the mature glycoprotein. Screening
      of truncated glycoprotein fragments with both mAbs confirmed the location of the
      epitope in the N-terminal region. Alignment of amino acid sequences from a range
      of RABV isolates indicated that the site was conserved in most viruses. Alignment
      with representatives of other lyssaviruses suggested that it is conserved within
      phylogroup I, which includes the European bat lyssaviruses, but not phylogroup
      II. A 12 aa synthetic peptide of this epitope was recognized by both mAbs and
      sera from a subset of rabies-vaccinated dogs. In a multimeric form, the peptide
      could induce an epitope-specific response following immunization in rabbits and
      mice.

PMID- 15483242
TI  - Effects of intrabodies specific for rotavirus NSP5 during the virus replicative
      cycle.
AB  - Intracellular antibodies or intrabodies (ICAbs) have great potential in protein
      knockout strategies for intracellular antigens. In this study, they have been
      used to investigate the role of the rotavirus non-structural protein NSP5 in the
      virus replication cycle. Intracellular antibody-capture technology was used to
      select single-chain Fv format (scFv) ICAbs against an NSP5 mutant. Five different
      specific ICAbs were selected and expressed in MA104 cells, in the scFv format, as
      cytoplasmic- and nuclear-tagged forms. By confocal microscopy, it was found that
      three of these ICAbs recognized the full-length wild-type NSP5 specifically,
      forming antigen-specific aggresomes in the cytoplasm of cotransfected cells.
      Expression of the ICAbs in rotavirus-infected cells largely reduced the assembly
      of viroplasms and cellular cytopathic effect. Replication of dsRNA was partially
      inhibited, despite there being no reduction in virus titre. These results
      demonstrate for the first time a key role for NSP5 during the virus replicative
      cycle.

PMID- 15483243
TI  - Vpx proteins of SIVmac239 and HIV-2ROD interact with the cytoskeletal protein
      alpha-actinin 1.
AB  - vpx genes of human immunodeficiency virus type 2 (HIV-2) and immunodeficiency
      viruses from macaques (SIVmac), sooty mangabeys (SIVsm) and red-capped mangabeys
      (SIVrcm) encode a 112 aa protein that is packed into virion particles via
      interaction with the p6 domain of p55(gag). Vpx localizes to the nucleus when
      expressed in the absence of other viral proteins. Moreover, Vpx is necessary for
      efficient nuclear import of the pre-integration complex (PIC) and critical for
      virus replication in quiescent cells, such as terminally differentiated
      macrophages and memory T cells. Vpx does not contain sequence elements that are
      homologous to previously characterized nuclear localization signals (NLSs).
      Therefore, it is likely that Vpx-dependent import of the PIC is mediated by
      interaction of Vpx with cellular proteins that do not belong to the classical
      import pathways. By using a yeast two-hybrid screen, alpha-actinin 1, a
      cytoskeletal protein, was identified to interact with SIVmac239 Vpx.
      Interestingly, deletion of the proline-rich C-terminal domain (aa 101-112) of
      Vpx, which is important for nuclear localization, resulted in loss of interaction
      with alpha-actinin 1. These findings suggest that the interaction with alpha
      actinin 1 may play an important role in the transport of Vpx to the nucleus and
      in Vpx-mediated nuclear import of the PIC.

PMID- 15483244
TI  - Non-invasive testing reveals a high prevalence of simian T-lymphotropic virus
      type 1 antibodies in wild adult chimpanzees of the Tai National Park, Cote
      d'Ivoire.
AB  - Little information is available on the prevalence of retrovirus infections in
      populations of non-human primates living in their natural habitats. To gain such
      information, methods were developed to detect antibodies to simian T-lymphotropic
      virus type 1 (STLV-1) in urine from wild chimpanzees. Samples from more than 74
      chimpanzees living in three communities in the Tai National Park, Cote d'Ivoire,
      were analysed. The prevalence of STLV-1 antibodies in adults and adolescents was
      significantly higher (35/49, 71.4 %) than that in infant and juvenile chimpanzees
      (3/31, 9.7 %).

PMID- 15483246
TI  - Successful induction of ovine pulmonary adenocarcinoma in lambs of different ages
      and detection of viraemia during the preclinical period.
AB  - Ovine pulmonary adenocarcinoma (OPA) can be reproduced consistently in neonatal
      lambs by intratracheal injection of inocula containing jaagsiekte sheep
      retrovirus (JSRV). In this study, clinical disease, confirmed pathologically as
      OPA, was induced in a high proportion of lambs that had been inoculated
      intratracheally with infectious lung fluid at 1, 3 and 6 months of age. The
      incubation periods, however, were longer in these three age groups than in 1-week
      old lambs that were used as controls. Viraemia was detected in all age groups
      before onset of clinical signs, but occurred later in older animals. These
      results suggest an age-dependent susceptibility to OPA that could be determined
      by the availability of JSRV target cells in the ovine lung. The feasibility of
      inducing OPA in older lambs and detecting JSRV viraemia in preclinical stages
      enables improved studies on the pathogenesis, assessment of vaccines, diagnosis
      and control of the disease.

PMID- 15483245
TI  - Natural simian foamy virus infection in wild-caught gorillas, mandrills and
      drills from Cameroon and Gabon.
AB  - A survey for the presence of simian foamy retroviruses (SFVs) was performed in 44
      wild-caught apes and monkeys, including 27 gorillas, 11 mandrills and six drills,
      originating from south Cameroon or Gabon. Combined serological and/or nested-PCR
      assays indicated SFV infection among five Gorilla gorilla gorilla, seven
      Mandrillus sphinx and two Mandrillus leucophaeus. Sequences of a 425 bp fragment
      of the integrase gene were obtained for 11 animals. Phylogenetic studies
      indicated that strains from gorillas, mandrills and drills each formed a highly
      supported phylogenetic clade with, moreover, the existence of two different
      gorilla SFVs. This study demonstrates for the first time that these animals are
      naturally infected with specific SFVs. In the context of simian-to-human
      interspecies transmission, the results confirm that such viruses can also infect
      humans, as the SFVs identified in wild-caught animals were the same as those
      recently reported as infecting hunters living in the same geographical areas.

PMID- 15483247
TI  - Analysis of the Drosophila gypsy endogenous retrovirus envelope glycoprotein.
AB  - gypsy is the only endogenous retrovirus of Drosophila whose infectious properties
      have been reported. Previous studies have shown an unexpected relationship
      between the gene encoding the putative envelope glycoprotein (Env) of gypsy and
      genes encoding the fusion protein of several baculoviruses. The fact that fusion
      proteins mediate membrane fusion suggests that Env of insect retroviruses might
      also have fusogenic properties. The results reported here indicate that gypsy Env
      mediates cell-to-cell fusion. Cleavage of the Env precursor was also studied; it
      is shown that this polypeptide is cleaved at a furin-like cleavage site. This is
      the first report that the env-like gene of insect retroviruses encodes a fusion
      protein.

PMID- 15483248
TI  - Reactivation of human herpesvirus 6 during ex vivo expansion of circulating CD34+
      haematopoietic stem cells.
AB  - Human herpesvirus 6 (HHV-6) replication was evaluated during in vitro expansion
      of CD34-positive cells that were selected from 11 peripheral blood progenitor
      cell (PBPC) samples. In order to permit cellular differentiation towards the
      myeloid lineage, PBPCs were cultured for 14-21 days in a liquid, serum-free
      medium supplemented with interleukin 1 (IL1), IL3, IL6, granulocyte-macrophage
      colony-stimulating factor, granulocyte colony-stimulating factor and stem-cell
      factor. Among the 10 cultures from HHV-6-seropositive patients, the late,
      alternatively spliced U100 viral mRNA was detected in five of them after PBPC
      culture for 14 or 21 days. Recovery of infectious virus from one of the
      expansions, associated with an increase of HHV-6 viral load and detection of the
      U100 spliced messenger, confirmed the occurrence of a complete replicative cycle.
      These data thus demonstrate for the first time that haematopoietic
      differentiation can lead to HHV-6 reactivation.

PMID- 15483249
TI  - Vascular endothelial and smooth muscle cells are unlikely to be major sites of
      latency of human cytomegalovirus in vivo.
AB  - Human cytomegalovirus (HCMV) is a frequent cause of major disease following
      primary infection or reactivation from latency in immunocompromised patients. It
      has also been suggested that there may be a link between HCMV and vascular
      disease. Both smooth muscle and endothelial cells are targets for primary
      infection with HCMV and have also been postulated as potential sites of HCMV
      latency. One of the most intensely studied sites of HCMV latency is the cells of
      the myeloid lineage; there is increasing evidence that the myeloid and
      endothelial lineages arise from a common precursor in the bone marrow, suggesting
      that endothelial cells could be another route of HCMV dissemination. However,
      using a highly sensitive PCR capable of detecting endogenous HCMV in myeloid
      cells, the HCMV genome in endothelial and smooth muscle cells isolated from the
      saphenous veins of seropositive patients was not detected. These data suggest
      that vascular endothelial and smooth muscle cells are unlikely to be important
      sites of HCMV latency in vivo.

PMID- 15483250
TI  - Translation of hepatitis B virus (HBV) surface proteins from the HBV pregenome
      and precore RNAs in Semliki Forest virus-driven expression.
AB  - Hepatitis B virus (HBV) pregenome RNA (pgRNA) serves as a translation template
      for the HBV core (HBc) protein and viral polymerase (Pol). HBV precore RNA
      (pcRNA) directs the synthesis of the precore (preC) protein, a precursor of the
      hepatitis B e antigen (HBeAg). pgRNA and pcRNA were expressed in the Semliki
      Forest virus (SFV) expression system. Besides the HBc and preC proteins, there
      was revealed the synthesis of all three forms of HBV surface (HBs) proteins: long
      (LHBs), middle (MHBs) and short (SHBs), the start codons of which are located
      more than 1000 nt downstream of the HBc and preC start codons. Moreover, other
      HBV templates, such as 3'-truncated pgRNA lacking 3' direct repeat and Pol mRNA,
      both carrying internally the HBs sequences, provided the synthesis of three HBs
      protein forms in the SFV-driven expression system. Maximal production of the HBs
      was provided by Pol mRNA, while HBc- and preC-producing templates showed
      relatively low internal translation of the HBs. These data allow the proposal of
      a ribosome leaky scanning model of internal translation initiation for HBs
      proteins. The putative functional role of such exceptional synthesis of the HBs
      proteins from the pgRNA and pcRNA templates in the natural HBV infection process
      needs further evaluation.

PMID- 15483251
TI  - Detection and characterization of cytoplasmic hepatitis B virus reverse
      transcriptase.
AB  - It was recently found that the Duck hepatitis B virus (DHBV) reverse
      transcriptase is primarily a non-encapsidated cytoplasmic molecule that is
      rapidly translated and has a very short half-life. Here, a non-encapsidated
      reverse transcriptase from the human Hepatitis B virus (HBV) was characterized.
      HBV polymerase accumulated in the cytoplasm in a manner similar to non
      encapsidated DHBV polymerase. However, the HBV polymerase accumulated at an
      apparently lower concentration and had a longer half-life than the DHBV enzyme,
      and it displayed no evidence of the post-translational modifications observed for
      DHBV. Unlike the DHBV polymerase, immunofluorescence detection of the HBV
      polymerase in cells was suppressed by the core protein, and this suppression
      occurred independently of encapsidation. This implies an interaction between the
      polymerase and core in addition to encapsidation, but the polymerase and core did
      not co-immunoprecipitate, so the interaction might not be direct. These data
      indicate that production of cytoplasmic, non-encapsidated polymerase is conserved
      among the hepadnaviral genera. Furthermore, conservation of the cytoplasmic form
      of the polymerase suggests that it might have function(s) in virus replication or
      pathology beyond copying the viral genome.

PMID- 15483252
TI  - Characterization and manipulation of the human adenovirus 4 genome.
AB  - Human adenovirus 4 (HAdV-4), the only serotype of the species HAdV-E to be
      isolated from man, was first identified by its association with outbreaks of
      acute respiratory disease in military recruits. To combat such outbreaks, a live,
      oral HAdV-4 vaccine that is delivered via an enteric-coated capsule was
      developed. This vaccine has been used for nearly 40 years and has been shown to
      be safe and efficacious. In this study, the complete DNA sequence (35 994 bp) of
      the vaccine strain is described and its genetic content is analysed. Phylogenetic
      comparisons confirmed that the closest sequenced relative of HAdV-4 is another
      serotype of HAdV-E that infects chimpanzees (SAdV-25) and that the great majority
      of genes in HAdV-E are related most closely to HAdV-B genes. By using the
      sequence data, a system was constructed to facilitate production of replication
      competent HAdV-4 recombinants.

PMID- 15483253
TI  - Dual role of the adenovirus pVI C terminus as a nuclear localization signal and
      activator of the viral protease.
AB  - Adenain, the protease produced by adenovirus, is regulated by formation of a
      heterodimer with an 11 aa peptide derived from the C terminus of another
      adenoviral protein, pVI. Here, the role of the basic motif KRRR, which is
      conserved in pVI sequences from human adenovirus serotypes, was investigated. It
      was shown that this motif is less important than the N- or C-terminal regions in
      the formation of the adenain-peptide heterodimer and in the activity of the
      subsequent complex. This motif, however, acted as a nuclear localization signal
      that was capable of targeting heterologous proteins to the nucleus, resulting in
      a distinctive intranuclear distribution consisting of discrete foci, which is
      similar to that found for pVI during adenovirus infection.

PMID- 15483254
TI  - Detection and in vitro and in vivo characterization of porcine circovirus DNA
      from a porcine-derived commercial pepsin product.
AB  - Non-pathogenic porcine circovirus type 1 (PCV1) and pathogenic PCV2 are
      widespread in swine herds. In this study, the detection and characterization of
      PCV1 and PCV2 DNA from porcine-derived commercial pepsin are reported. The
      complete genomic sequences of the pepsin-derived PCV1 and PCV2 share 76 %
      nucleotide sequence identity with each other and 95-99 % identity with respective
      North American PCV1 and PCV2 isolates. However, the PCV-contaminated pepsin lacks
      infectivity in PK-15 cells. To further assess the infectivity of the
      contaminating pepsin in vivo, 16 5-week-old, specific-pathogen-free pigs were
      divided randomly into three groups: pigs in group 1 (n=5) were each inoculated
      intramuscularly and intranasally with 4 ml PBS buffer as negative controls, those
      in group 2 (n=6) were each inoculated with 400 mg contaminated pepsin dissolved
      in 4 ml PBS and those in group 3 (n=5) were each inoculated with 4 x 10(4.3)
      TCID(50) PCV2 as positive controls. PCV2 viraemia, seroconversion and
      pathological lesions were detected in group 3 pigs, but not in group 1 or 2 pigs,
      confirming that the contaminating PCVs were non-infectious. Nevertheless, the
      detection of PCV DNA in a porcine-derived commercial product raises concern for
      potential human infection through xenotransplantation.

PMID- 15483255
TI  - Constraints imposed by supercoiling on in vitro amplification of polyomavirus
      DNA.
AB  - Previous attempts to identify oncogenic polyomaviruses in human cancers have
      yielded conflicting results, even with the application of PCR technology. Here,
      it was considered whether the topological features of the polyomavirus genome
      interfere with efficient PCR amplification. Plasmid and SV40 DNAs were used as a
      model system for comparing the amplification efficiency of supercoiled, circular
      relaxed and linear templates. It was found that detection of circular templates
      required 10 times more molecules than detection of identical but linear
      templates. Supercoiling hindered the in vitro amplification of SV40 circles by a
      factor of 10, and erratic amplification of supercoiled SV40 occurred with
      subpicogram amounts of template. Accordingly, topoisomerase I treatment of DNA
      improved the PCR detection of supercoiled SV40, significantly decreasing the
      number of false-negative samples. Previously described, yet controversial,
      polyomavirus presence in human tissues should be reconsidered and topoisomerase I
      sensitive polyomavirus amplification might help to detect polyomavirus genomes in
      mammalian tissues.

PMID- 15483256
TI  - Cherry chlorotic rusty spot and Amasya cherry diseases are associated with a
      complex pattern of mycoviral-like double-stranded RNAs. I. Characterization of a
      new species in the genus Chrysovirus.
AB  - Cherry chlorotic rusty spot (CCRS) and Amasya cherry disease (ACD) display
      similar symptoms and are associated with a series of dsRNAs. However, a direct
      comparison has been lacking. Here, a side-by-side analysis confirmed that both
      diseases were symptomatologically very similar, as were the number (10-12) and
      size of their associated dsRNAs. Sequence determination of four of these dsRNAs
      revealed that they were essentially identical for CCRS and ACD. The largest (3399
      bp), which potentially encoded a protein of 1087 aa with the eight motifs
      conserved in RNA-dependent RNA polymerases of dsRNA mycoviruses, had the highest
      similarity to those coded by dsRNA 1 of viruses belonging to the genus
      Chrysovirus and was termed CCRS or ACD chrys-dsRNA 1. The three closely migrating
      dsRNAs had the properties of the other components of a chrysovirus and in CCRS
      and ACD versions, respectively, were chrys-dsRNA 2 (3125 and 3128 bp), chrys
      dsRNA 3 (2833 bp) and chrys-dsRNA 4 (2499 and 2498 bp), potentially encoding the
      major capsid protein (993 and 994 aa) and two proteins (884 and 677 aa,
      respectively) of unknown function. The four 5'- and 3'-UTRs shared internal
      similarities and had conserved GAAAAUUAUGG and AUAUGC termini, respectively. The
      5'-UTRs contained the 'Box 1' motif followed by a stretch rich in CAA, CAAA and
      CAAAA repeats, characteristic of chrysovirus dsRNAs. Because species of the genus
      Chrysovirus have only been described as infecting fungi, this suggests a fungal
      aetiology for CCRS and ACD, a proposal supported by the properties of two other
      CCRS- and ACD-associated dsRNAs (see accompanying paper by Coutts et al., 2004,
      in this issue).

PMID- 15483257
TI  - Cherry chlorotic rusty spot and Amasya cherry diseases are associated with a
      complex pattern of mycoviral-like double-stranded RNAs. II. Characterization of a
      new species in the genus Partitivirus.
AB  - Two dsRNAs from cherry trees affected with cherry chlorotic rusty spot (CCRS) in
      Italy and Amasya cherry disease (ACD) in Turkey were sequenced and found to be
      essentially identical. The larger dsRNA 1 (2021 or 2006 bp, respectively)
      potentially encoded a protein of 621 aa containing the conserved motifs of the
      RNA-dependent RNA polymerases (RdRp) of dsRNA mycoviruses, having highest
      similarity with those in the genus Partitivirus. The smaller dsRNA 2 (1841 or
      1839 bp, respectively) had properties consistent with the second genomic
      component of a partitivirus and potentially encoded the coat protein (CP) of 504
      aa. Phylogenetic analysis based on the RdRp and CP was coincidental and indicated
      that species in the genus Partitivirus could be separated into two subgroups.
      Because species of this genus only infect fungi, these observations suggest a
      fungal aetiology for CCRS and ACD, further substantiating a previous proposal
      (see accompanying paper by Covelli et al., 2004, in this issue).

PMID- 15483258
TI  - Cucumber mosaic virus 2b protein compensates for restricted systemic spread of
      Potato virus Y in doubly infected tobacco.
AB  - Tobacco plants (Nicotiana tabacum cv. Xanthi-nc) inoculated with a necrotic
      strain of Potato virus Y (PVY, T01 isolate) developed necrotic symptoms in some
      systemically infected leaves, but not in younger leaves. However, PVY expressed
      distinct symptoms not only in the older leaves, but also in the younger leaves,
      of plants that had been doubly inoculated with PVY and with Cucumber mosaic virus
      (CMV, strain Pepo). A tissue blot immunoassay of tissues from various positions
      of the stem detected PVY weakly in each stem, but not in the shoot apex, of
      singly infected plants, whereas PVY was detected at high levels in almost all
      sections of doubly infected plants. CMV was also detected at high levels in
      sections of singly and doubly infected plants. Immunohistochemistry of stem
      tissues showed that in singly infected plants, PVY was confined to external
      phloem cells and was not detected in internal phloem cells. However, in doubly
      infected plants, PVY was distributed uniformly throughout whole tissues,
      including the external phloem, xylem parenchyma and internal phloem cells. In
      plants that were doubly infected with PVY and Pepo Delta 2b, a modified CMV that
      cannot translate the 2b protein, the spread of PVY was restricted as in singly
      infected plants. These results suggested that the plant host has a counterdefence
      mechanism that restricts systemic spread of PVY T01, and that the 2b protein of
      CMV strain Pepo negates this restriction.

PMID- 15483259
TI  - RNA silencing-suppressor function of Turnip crinkle virus coat protein cannot be
      attributed to its interaction with the Arabidopsis protein TIP.
AB  - The interaction of the coat protein (CP) of Turnip crinkle virus (TCV) with a
      host protein, TCV-interacting protein (TIP), from Arabidopsis thaliana has been
      reported previously. This interaction correlates with the ability of TCV CP to
      elicit the resistance response that is mediated by the resistance gene HRT in
      Arabidopsis ecotype Di-17. It has also been established that TCV CP is a
      suppressor of RNA silencing, a process by which the host plant targets viral RNA
      for degradation. These results have led to the speculation that TIP might be a
      component of the RNA-silencing pathway and that TCV CP suppresses RNA silencing
      through its interaction with TIP. In the current report, a number of TCV CP
      mutants have been investigated for their ability to suppress RNA silencing. These
      mutants include single amino acid substitution mutants that are known to have
      lost their ability to interact with TIP, as well as deletion mutants of TCV CP
      that are of different sizes and from different regions of the protein. Results
      showed that each of the single amino acid substitution mutants tested retained
      high levels of RNA silencing-suppressor activity. In addition, a mutant
      containing a 5 aa deletion in the region that is known to be critical for TIP
      interaction retained the ability to suppress RNA silencing significantly. Larger
      deletions in all regions of TCV CP abolished silencing-suppressor activity. It
      can be concluded from these results that the RNA silencing-suppressor activity of
      TCV CP cannot be attributed to its ability to interact directly with TIP.

PMID- 15483260
TI  - Maintenance of coat protein N-terminal net charge and not primary sequence is
      essential for zucchini yellow mosaic virus systemic infectivity.
AB  - Zucchini yellow mosaic virus (ZYMV) surface exposed coat protein (CP) N-terminal
      domain (Nt) is 43 aa long and contains an equal number of positively and
      negatively charged amino acid residues (CP-Nt net charge = 0). A ZYMV-AGII
      truncation mutant lacking the first 20 aa of its CP-Nt (AGII-CP Delta 20; CP-Nt
      net charge = +2) was found to be systemically non-infectious even though AGII
      mutants harbouring larger CP-Nt deletions were previously demonstrated to be
      fully infectious. Nevertheless, AGII-CP Delta 20 infectivity was restored by
      fusion to its CP-Nt two Asp residues or a negatively charged Myc peptide, both
      predicted to neutralize CP-Nt net positive charge. To evaluate further the
      significance of CP-Nt net charge for AGII infectivity, a series of CP-Nt net
      charge mutants was generated and analysed for systemic infectivity of squash
      plants. AGII-CP(KKK) harbouring a CP-Nt amino fusion of three Lys residues (CP-Nt
      net charge = +3) was not systemically infectious. Addition of up to four Asp
      residues to CP-Nt did not abolish virus infectivity, although certain mutants
      were genetically unstable and had delayed infectivity. Addition of five
      negatively charged residues abolished infectivity (AGII-CP(DDDDD); CP-Nt net
      charge = -5) even though a recombinant CP(DDDDD) could assemble into potyviral
      like particle in bacteria. Neutralization of CP-Nt net charge by fusing Asp or
      Lys residues recovered infectivity of AGII-CP(KKK) and AGII-CP(DDDDD). GFP
      tagging of these mutants has demonstrated that both viruses have defective cell
      to-cell movement. Together, these findings suggest that maintenance of CP-Nt net
      charge and not primary sequence is essential for ZYMV infectivity.

PMID- 15483261
TI  - Surface-exposed C-terminal amino acids of the small coat protein of Cowpea mosaic
      virus are required for suppression of silencing.
AB  - The small (S) coat protein of Cowpea mosaic virus (CPMV) has been identified
      previously as a virus-encoded suppressor of post-transcriptional gene silencing
      (PTGS). Deletions within the C-terminal 24 aa of this protein affect the yield
      and systemic spread of the virus, suggesting that the C-terminal amino acids of
      the S protein, which are exposed on the surface of assembled virus particles, may
      be responsible for the suppressor activity. To investigate this, versions of CPMV
      RNA-2 with deletions at the C terminus of the S protein were tested for their
      ability to counteract PTGS in leaf-patch tests. The results showed that the C
      terminal 16 aa of the S protein are particularly important for suppressing PTGS
      and that these amino acids are virus-specific and cannot be substituted by the
      equivalent sequence from the related virus Bean pod mottle virus.

PMID- 15483262
TI  - Complete genome sequence of Mycoreovirus-1/Cp9B21, a member of a novel genus
      within the family Reoviridae, isolated from the chestnut blight fungus
      Cryphonectria parasitica.
AB  - Mycoreovirus 1 (MYRV-1) is the type species of the newly described genus
      Mycoreovirus of the large virus family Reoviridae. The virus was isolated from a
      hypovirulent strain (9B21) of the chestnut blight fungus, Cryphonectria
      parasitica. A previous study showed that double-shelled particles introduced to
      fungal spheroplasts resulted in stably infected colonies. Of the 11 double
      stranded RNA genomic segments (S1-S11), the three largest (S1-S3) were sequenced
      previously and shown to have moderate levels of similarity to the homologous
      segments of mammal-pathogenic coltiviruses (Eyach virus and Colorado tick fever
      virus) and another fungus-infecting reovirus, Mycoreovirus 3 of Rosellinia
      necatrix strain W370 (MYRV-3/RnW370). The sequences of the remaining segments (S4
      S11) are reported here. All of the segments have single ORFs on their positive
      strands and the terminal sequences 5'-GAUCA----GCAGUCA-3' are conserved among
      currently and previously sequenced segments. Oligo-cap analysis showed that the
      positive strands of the genomic segments are capped, whereas the negative strands
      are not. Similarities among the four evolutionarily related viruses include low
      or moderate levels of amino acid sequence identity (14.7-34.2 %) and isoelectric
      points among equivalent polypeptides, e.g. proteins encoded by segments S4 and S5
      of the four viruses. Phylogenetic analysis indicated that MYRV-1/Cp9B21 is
      related more closely to MYRV-3/RnW370 than to the coltiviruses. An interesting
      dissimilarity is found in codon-choice pattern among the four viruses, i.e. MYRV
      1/Cp9B21 segments have a lower frequency of [XYG+XYC] than corresponding segments
      of the other viruses, suggesting a possible adjustment of virus codon usage to
      their host environments.

PMID- 15483263
TI  - Propagation of a protease-resistant form of prion protein in long-term cultured
      human glioblastoma cell line T98G.
AB  - Human prion diseases, such as Creutzfeldt-Jakob disease (CJD), a lethal,
      neurodegenerative condition, occur in sporadic, genetic and transmitted forms.
      CJD is associated with the conversion of normal cellular prion protein (PrP(C))
      into a protease-resistant isoform (PrP(res)). The mechanism of the conversion has
      not been studied in human cell cultures, due to the lack of a model system. In
      this study, such a system has been developed by culturing cell lines. Human
      glioblastoma cell line T98G had no coding-region mutations of the prion protein
      gene, which was of the 129 M/V genotype, and expressed endogenous PrP(C)
      constitutively. T98G cells produced a form of proteinase K (PK)-resistant prion
      protein fragment following long-term culture and high passage number; its
      deglycosylated form was approximately 18 kDa. The PK-treated PrP(res) was
      detected by immunoblotting with the mAb 6H4, which recognizes residues 144-152,
      and a polyclonal anti-C-terminal antibody, but not by the mAb 3F4, which
      recognizes residues 109-112, or the anti-N-terminal mAb HUC2-13. These results
      suggest that PrP(C) was converted into a proteinase-resistant form of PrP(res) in
      T98G cells.

PMID- 15483264
TI  - Identification of central nervous system genes involved in the host response to
      the scrapie agent during preclinical and clinical infection.
AB  - Genes that are expressed differentially in the central nervous system of mice
      during infection with mouse-adapted scrapie agents were identified in this study.
      cDNA microarrays were used to examine gene-expression profiles at early, middle
      (preclinical) and late (clinical) time points after inoculation. A number of
      genes that showed significant changes in expression during the clinical stage of
      disease were identified. Of these, 138 were upregulated and 20 were
      downregulated. A smaller number of genes showed differential expression at the
      early and middle stages of the disease time course. These genes are interesting,
      as they may reflect biological processes that are involved in the molecular
      pathogenesis of the prion agent. At present, little is known about the early
      events in the disease process that trigger neurodegeneration. Perhaps most
      interestingly, one group of genes that exhibited decreased expression in all
      tested stages of the disease was identified in this study. This cluster included
      four transcripts representing haematopoietic system-related genes, which suggests
      that the haematopoietic system is involved in the disease process from an early
      stage.

PMID- 15483265
TI  - Cell-surface retention of PrPC by anti-PrP antibody prevents protease-resistant
      PrP formation.
AB  - The C-terminal portion of the prion protein (PrP), corresponding to a protease
      resistant core fragment of the abnormal isoform of the prion protein (PrP(Sc)),
      is essential for prion propagation. Antibodies to the C-terminal portion of PrP
      are known to inhibit PrP(Sc) accumulation in cells persistently infected with
      prions. Here it was shown that, in addition to monoclonal antibodies (mAbs) to
      the C-terminal portion of PrP, a mAb recognizing the octapeptide repeat region in
      the N-terminal part of PrP that is dispensable for PrP(Sc) formation reduced
      PrP(Sc) accumulation in cells persistently infected with prions. The 50%
      effective dose was as low as approximately 1 nM, and, regardless of their epitope
      specificity, the inhibitory mAbs shared the ability to bind cellular prion
      protein (PrP(C)) expressed on the cell surface. Flow cytometric analysis revealed
      that mAbs that bound to the cell surface during cell culture were not
      internalized even after their withdrawal from the growth medium. Retention of the
      mAb-PrP(C) complex on the cell surface was also confirmed by the fact that
      internalization was enhanced by treatment of cells with dextran sulfate. These
      results suggested that anti-PrP mAb antagonizes PrP(Sc) formation by interfering
      with the regular PrP(C) degradation pathway.

PMID- 15483266
TI  - Abnormal prion protein in genetically resistant sheep from a scrapie-infected
      flock.
AB  - The central molecular event in transmissible spongiform encephalopathies, such as
      scrapie in sheep, is the accumulation in tissues of an abnormal isoform of the
      cellular prion protein. A previous investigation of 26 sheep showed that the
      accumulation of PrP(res) in brain correlated more with the prnp genotype than
      with the severity of the clinical disease. Here, the ability of a sandwich ELISA
      to detect PrP(res) distribution in the brain was demonstrated.
      Immunohistochemistry also strongly supported the hypothesis that the dorsal motor
      nucleus of the vagus nerve is the possible entry site in the brain for the
      scrapie agent. Remarkably, three asymptomatic (or possibly asymptomatic for
      scrapie) sheep carrying an allele known to be associated with clinical scrapie
      resistance (ARR), which were negative for the detection of PrP(res) by Western
      blotting and immunohistochemistry, were positive for the presence of PrP(res) by
      ELISA, raising the possibility of carriers resistant to the disease and possibly
      contributing to the persistence of scrapie in certain flocks.

PMID- 15483267
TI  - Identification of putative atypical scrapie in sheep in Portugal.
AB  - Experimental transmission of bovine spongiform encephalopathy to sheep has
      prompted the implementation of a surveillance plan of scrapie in small ruminants
      by the European Union in all member states. Since its start over 30,000 animals
      have been tested, and the first seven cases of sheep with detectable PrP(res)
      deposition in the central nervous system have been identified in Portugal.
      Notably, the pattern of PrP(res) distribution in the brainstem was different from
      that previously described for scrapie and consistent in all seven animals.
      Moreover, the profile of the electrophoretic mobility of PrP(res) after
      proteinase K treatment was equivalent in all cases analysed but distinct from
      that observed for scrapie. Notably, four animals had genotypes rarely associated
      with scrapie, including one animal homozygous for A(136)R(154)R(171). There were
      no cases found to exhibit vacuolation, a pattern of PrP(res) distribution or
      PrP(res) electrophoretic mobility corresponding to scrapie. These data reveal a
      putative atypical scrapie strain in Portugal not linked to specific Prnp
      genotypes.

PMID- 15483268
TI  - Sequencing, expression, and enzymatic characterization of beta-hexosaminidase in
      rabbit lacrimal gland and primary cultured acinar cells.
AB  - The lysosomal enzyme, beta-hexosaminidase, exists as two major isoforms; HexA and
      HexB. HexA is an alpha beta-subunit heterodimer and HexB a beta-subunit
      homodimer. Both isoforms can remove nonreducing beta-N-acetyl-D-glucosamine
      residues, whereas HexA hydrolyzes charged substrates as G(M2) gangliosides as
      well. beta-Hexosaminidase is present in both human and rabbit tear fluid and is
      secreted from rabbit lacrimal gland acinar cells in primary culture on
      stimulation with secretagogs. To further characterize the enzyme, the alpha- and
      beta-subunit mRNA expression was explored in rabbit lacrimal gland tissue as well
      as in cultured cells. Possible correlation between mRNA expression and HexA
      specific enzymatic activity was also investigated. Because existing beta
      hexosaminidase antibodies are unable to recognize the rabbit enzyme, cloning and
      sequencing of the alpha- and beta-subunits were performed. Sequencing of the
      these subunits indicate that both are highly conserved between human, mouse, and
      rabbit. In contrast to the beta-subunit, showing an even mRNA expression between
      tissue and cultured cells, the level of alpha-subunit expression was higher in
      cultured acinar cells compared to tissue, with no alteration after cell
      stimulation. A minor but significant increase in total beta-hexosaminidase as
      well as HexA activity was observed in cultured cells compared to tissue.
      Enzymatic activity assays also revealed that HexA is the dominating isoform of
      beta-hexosaminidase in lacrimal gland and cultured acinar cells.

PMID- 15483269
TI  - Not core 2 beta 1,6-N-acetylglucosaminyltransferase-2 or -3 but -1 regulates
      sialyl-Lewis x expression in human precursor B cells.
AB  - Sialyl-Lewis x (sLeX), one of the major selectin ligands, is expressed on T and B
      cells in a differentiation or activation stage-specific manner. We have
      demonstrated before that sLeX expression and core 2 beta 1,6-N
      acetylglucosaminyltransferase (C2GnT) were simultaneously regulated during
      precursor B (pre-B) cell differentiation. Three C2GnT family genes, designated
      C2GnT-1, -2, and -3, were previously identified, but their roles have not been
      fully examined. In this study, we have investigated the roles of C2GnTs in the
      regulation of sLeX expression level during pre-B cell differentiation comparing
      with alpha 1,3fucosyltransferase-VII (FucT-VII) and alpha 2,3sialyltransferase-IV
      (ST3Gal-IV). Overexpression of not FucT-VII and ST3Gal-IV but C2GnT-1 blocked the
      down-regulation of sLeX expression by differentiation induction. Neither C2GnT-2
      nor -3 but C2GnT-1 transcript was mainly expressed in B lineage cell lines and
      bone marrow-derived B lineage cells. Significant down-regulation of C2GnT-1 of
      the three C2GnTs was observed in KM3 cells during differentiation. The expression
      of C2GnT-1 correlated well to sLeX expression and differentiation stage.
      Furthermore, introduction of short interfering RNA against C2GnT-1 markedly
      reduced C2GnT-1 expression and resulted in down-regulation of sLeX expression.
      These results suggest that not the other glycosyltransferases but C2GnT-1
      regulates sLeX expression level during differentiation of pre-B cells, providing
      the cells with substrate of sLeX structure biosynthesis.

PMID- 15483270
TI  - Regulation of intestinal ontogeny: effect of glucocorticoids and luminal microbes
      on galactosyltransferase and trehalase induction in mice.
AB  - Intestinal maturation can be influenced by intrinsic factors (glucocorticoid
      hormones) and by extrinsic factors (resident microflora); their relative roles in
      ontogeny of mouse intestinal trehalase expression, a marker of general gut
      development, and of beta1,4-galactosyltransferase (beta GT), a marker of
      glycosyltransferase development, were investigated. In conventional (CONV) mice,
      beta GT and trehalase gene expression rapidly increased to adult levels by the
      fourth postnatal week. In germ-free (GF) mice, beta GT expression remained at
      initial low levels and was rapidly induced on reintroduction of luminal microbes
      of the adult gut but not of microbes characteristic of the suckling gut. Similar
      developmental patterns were observed for colonic galactosyl beta1,4-linked
      glycoconjugates, products of beta GT activity. These results indicate an
      essential role for microbes in the ontogeny of beta GT. In both CONV and GF mice,
      cartisone acetate (CA) precociously accelerated the ontogeny of beta GT and
      trehalase until maturation of the gut occurred (day 22). In the mature gut of
      CONV mice, both beta GT and trehalase are elevated and insensitive to CA; in GF
      mature mice, the expression of beta GT remains low, whereas the expression of
      trehalase was at mature levels, regardless of CA treatment. These changes in
      enzyme activity were accompanied by parallel changes in mRNA, implying
      transcriptional regulation. Thus both microbes and cortisone regulate gut
      ontogeny, but only suckling gut responds to CA, an intrinsic factor, whereas
      adult gut beta GT expression remains sensitive to microflora, an extrinsic
      factor. However, induction of the adult pattern of glycosyltransferase expression
      in mature gut requires colonization by microflora typical of adult gut,
      suggesting an essential role for intestinal colonization in the ontogeny of
      normal intestinal mucosal cell surface glycoconjugate receptors.

PMID- 15483271
TI  - Dimannosyldiacylglycerol serves as a lipid anchor precursor in the assembly of
      the membrane-associated lipomannan in Micrococcus luteus.
AB  - Based on recent analytical and enzymological studies, a topological model for the
      role of alpha-D-mannosyl-(1-->3)-alpha-D-mannosyl-(1-->3)-diacylglycerol (Man(2)
      DAG) as a lipid anchor precursor and mannosylphosphorylundecaprenol (Man-P-Und)
      as a mannosyl donor in the assembly of a membrane-associated lipomannan (LM) in
      Micrococcus luteus has been proposed. In this study, a [(3)H]mannose-suicide
      selection procedure has been used to identify temperature-sensitive (ts) mutants
      defective in LM assembly. Two micrococcal mutants with abnormal levels of Man(2)
      DAG and LM at the nonpermissive temperature (37 degrees C), mms1 and mms2, have
      been isolated and characterized. In vivo and in vitro biochemical assays indicate
      that mms1 cells have a defect in the mannosyltransferase catalyzing the
      conversion of Man-DAG to Man(2)-DAG, and mms2 has a temperature-sensitive defect
      in the synthesis of Man-P-Und. Because mms1 cells are depleted of endogenous
      Man(2)-DAG, membranes from this mutant efficiently converted purified, exogenous
      [(3)H]Man(2)-DAG to [(3)H]LM by a Man-P-Und-dependent process. An obligatory role
      for Man-P-Und as a mannosyl donor in the elongation process was also demonstrated
      by showing that the conversion of exogenous [(3)H]Man(2)-DAG to [(3)H]LM by
      membranes from mms1 cells in the presence of GDP-Man was inhibited by amphomycin.
      In addition, consistent with Man(2)-DAG serving as a lipid anchor precursor for
      LM assembly, endogenous, prelabeled [(3)H]Man(2)-DAG was converted to [(3)H]LM
      when membranes from mms2 cells were incubated with purified, exogenous Man-P-Und.
      These studies provide the first direct proof for the role of Man(2)-DAG as the
      lipid anchor precursor for LM, and suggest that Man(2)-DAG may be essential for
      the normal growth of M. luteus cells.

PMID- 15483272
TI  - Images in clinical medicine. Ureteral obstruction in pregnancy.

PMID- 15483274
TI  - Problems with drug-eluting coronary stents--the FDA perspective.

PMID- 15483273
TI  - Controlling health care costs.

PMID- 15483275
TI  - A black-box warning for antidepressants in children?

PMID- 15483277
TI  - Corporate treatment for the ills of academic medicine.

PMID- 15483276
TI  - Antidepressants and pediatric depression--the risk of doing nothing.

PMID- 15483278
TI  - Cardiopulmonary bypass after 50 years.

PMID- 15483279
TI  - A randomized trial comparing conventional and endovascular repair of abdominal
      aortic aneurysms.
AB  - BACKGROUND: Although the initial results of endovascular repair of abdominal
      aortic aneurysms were promising, current evidence from controlled studies does
      not convincingly show a reduction in 30-day mortality relative to that achieved
      with open repair. METHODS: We conducted a multicenter, randomized trial comparing
      open repair with endovascular repair in 345 patients who had received a diagnosis
      of abdominal aortic aneurysm of at least 5 cm in diameter and who were considered
      suitable candidates for both techniques. The outcome events analyzed were
      operative (30-day) mortality and two composite end points of operative mortality
      and severe complications and operative mortality and moderate or severe
      complications. RESULTS: The operative mortality rate was 4.6 percent in the open
      repair group (8 of 174 patients; 95 percent confidence interval, 2.0 to 8.9
      percent) and 1.2 percent in the endovascular-repair group (2 of 171 patients; 95
      percent confidence interval, 0.1 to 4.2 percent), resulting in a risk ratio of
      3.9 (95 percent confidence interval, 0.9 to 32.9). The combined rate of operative
      mortality and severe complications was 9.8 percent in the open-repair group (17
      of 174 patients; 95 percent confidence interval, 5.8 to 15.2 percent) and 4.7
      percent in the endovascular-repair group (8 of 171 patients; 95 percent
      confidence interval, 2.0 to 9.0 percent), resulting in a risk ratio of 2.1 (95
      percent confidence interval, 0.9 to 5.4). CONCLUSIONS: On the basis of the
      overall results of this trial, endovascular repair is preferable to open repair
      in patients who have an abdominal aortic aneurysm that is at least 5 cm in
      diameter. Long-term follow-up is needed to determine whether this advantage is
      sustained.

PMID- 15483280
TI  - Growth patterns and the risk of breast cancer in women.
AB  - BACKGROUND: Adult height and body-mass index influence the risk of breast cancer
      in women. Whether these associations reflect growth patterns of the fetus or
      growth during childhood and adolescence is unknown. METHODS: We investigated the
      association between growth during childhood and the risk of breast cancer in a
      cohort of 117,415 Danish women. Birth weight, age at menarche, and annual
      measurements of height and weight were obtained from school health records. We
      used the data to model individual growth curves. Information on vital status, age
      at first childbirth, parity, and diagnosis of breast cancer was obtained through
      linkages to national registries. RESULTS: During 3,333,359 person-years of follow
      up, 3340 cases of breast cancer were diagnosed. High birth weight, high stature
      at 14 years of age, low body-mass index (BMI) at 14 years of age, and peak growth
      at an early age were independent risk factors for breast cancer. Height at 8
      years of age and the increase in height during puberty (8 to 14 years of age)
      were also associated with breast cancer. The attributable risks of birth weight,
      height at 14 years of age, BMI at 14 years of age, and age at peak growth were 7
      percent, 15 percent, 15 percent, and 9 percent, respectively. No effect of
      adjusting for age at menarche, age at first childbirth, and parity was observed.
      CONCLUSIONS: Birth weight and growth during childhood and adolescence influence
      the risk of breast cancer.

PMID- 15483281
TI  - The role of ischemic mitral regurgitation in the pathogenesis of acute pulmonary
      edema.
AB  - BACKGROUND: Acute mitral regurgitation may cause pulmonary edema, but the
      pathogenetic role of chronic ischemic mitral regurgitation, a dynamic condition,
      has not yet been characterized. METHODS: We prospectively studied 28 patients
      (mean [+/-SD] age, 65+/-11 years) with acute pulmonary edema and left ventricular
      systolic dysfunction and 46 patients without a history of acute pulmonary edema.
      The two groups were matched for all baseline characteristics. Patients underwent
      quantitative Doppler echocardiography during exercise. Exercise-induced changes
      in the left ventricular volume, the ejection fraction, the mitral regurgitant
      volume, the effective regurgitant orifice area, and the transtricuspid pressure
      gradient were compared in patients with and without acute pulmonary edema.
      RESULTS: The two groups had similar clinical and baseline echocardiographic
      characteristics. They also had similar exercise-induced changes in heart rate,
      systolic blood pressure, and left ventricular volumes. In the univariate
      analysis, patients with recent pulmonary edema had a much higher increase than
      did the patients without pulmonary edema in mitral regurgitant volume (26+/-14 ml
      vs. 5+/-14 ml, P<0.001), the effective regurgitant orifice area (16+/-10 mm2 vs.
      2+/-9 mm2, P<0.001), and the transtricuspid pressure gradient (29+/-10 mm Hg vs.
      13+/-11 mm Hg, P<0.001). In the multivariate analysis, exercise-induced changes
      in the effective regurgitant orifice area (P<0.001), in the transtricuspid
      pressure gradient (P=0.001), and in the left ventricular ejection fraction
      (P=0.02) were independently associated with a history of recent pulmonary edema.
      CONCLUSIONS: In patients with left ventricular systolic dysfunction, acute
      pulmonary edema is associated with the dynamic changes in ischemic mitral
      regurgitation and the resulting increase in pulmonary vascular pressure.

PMID- 15483282
TI  - Fresh whole blood versus reconstituted blood for pump priming in heart surgery in
      infants.
AB  - BACKGROUND: In an attempt to reduce the coagulopathic and inflammatory responses
      seen after cardiopulmonary bypass, the use of fresh whole blood during heart
      operations has become the standard of care for neonates and infants at many
      institutions. We compared the use of fresh whole blood with the use of a
      combination of packed red cells and fresh-frozen plasma (reconstituted blood) for
      priming of the cardiopulmonary bypass circuit. METHODS: We conducted a single
      center, randomized, double-blind, controlled trial involving children less than
      one year of age who underwent open-heart surgery. Patients were assigned to
      receive either fresh whole blood that had been collected not more than 48 hours
      previously (96 patients) or reconstituted blood (104 patients) for bypass-circuit
      priming. Clinical outcomes and serologic measures of systemic inflammation and
      myocardial injury were compared between the groups. RESULTS: The group that
      received reconstituted blood had a shorter stay in the intensive care unit than
      the group that received fresh whole blood (70.5 hours vs. 97.0 hours, P=0.04).
      The group that received reconstituted blood also had a smaller cumulative fluid
      balance at 48 hours (-6.9 ml per kilogram of body weight vs. 28.8 ml per
      kilogram, P=0.003). Early postoperative chest-tube output, blood-product
      transfusion requirements, and levels of serum mediators of inflammation and
      cardiac troponin I were similar in the two groups. CONCLUSIONS: The use of fresh
      whole blood for cardiopulmonary bypass priming has no advantage over the use of a
      combination of packed red cells and fresh-frozen plasma during surgery for
      congenital heart disease. Moreover, circuit priming with fresh whole blood is
      associated with an increased length of stay in the intensive care unit and
      increased perioperative fluid overload.

PMID- 15483284
TI  - Pulmonary arterial hypertension.

PMID- 15483283
TI  - Prosthetic-joint infections.

PMID- 15483285
TI  - Images in clinical medicine. A brilliant case of erythrasma.

PMID- 15483286
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 31-2004. A four-year-old boy with hypoxemia.

PMID- 15483287
TI  - Abdominal aortic aneurysm--open versus endovascular repair.

PMID- 15483288
TI  - Breast cancer--early life matters.

PMID- 15483289
TI  - Dynamic mitral regurgitation--more than meets the eye.

PMID- 15483290
TI  - Building an intestine--architectural contributions of commensal bacteria.

PMID- 15483291
TI  - Ethics of embryonic stem cells.

PMID- 15483292
TI  - Bevacizumab in colorectal cancer.

PMID- 15483293
TI  - Oxaliplatin in colon cancer.

PMID- 15483294
TI  - Treatment of warts.

PMID- 15483295
TI  - Chronic thromboembolic pulmonary hypertension.

PMID- 15483296
TI  - Neuropathic diabetic foot ulcers.

PMID- 15483298
TI  - What community? What lifestyle?

PMID- 15483297
TI  - Spectrophotometry for xanthochromia.

PMID- 15483299
TI  - Psychosocial work environment and health: new evidence.

PMID- 15483300
TI  - The promiscuous 10%?

PMID- 15483301
TI  - Rebuilding health care in Iraq.

PMID- 15483304
TI  - Measures of health inequalities: part 2.
AB  - This is the second part of a two part glossary on measures of health
      inequalities.

PMID- 15483303
TI  - Genetics and public health--evolution, or revolution?
AB  - During the 19th and early 20th century, public health and genetics shared common
      ground through similar approaches to health promotion in the population. By the
      mid-20th century there was a division between public health and genetics, with
      eugenicists estranged and clinical genetics focused on single gene disorders,
      usually only relevant to small numbers of people. Now through a common interest
      in the aetiology of complex diseases such as heart disease and cancer, there is a
      need for people working in public health and genetics to collaborate. This is not
      a comfortable convergence for many, particularly those in public health. Nine
      main concerns are reviewed: fear of eugenics; genetic reductionism; predictive
      power of genes; non-modifiable risk factors; rights of individuals compared with
      populations; resource allocation; commercial imperative; discrimination; and
      understanding and education. This paper aims to contribute to the thinking and
      discussion about an evolutionary, multidisciplinary approach to understanding,
      preventing, and treating complex diseases.

PMID- 15483305
TI  - Influence of sociodemographic and neighbourhood factors on self rated health and
      quality of life in rural communities: findings from the Agriproject in the
      Republic of Ireland.
AB  - OBJECTIVE: To examine the influence of sociodemographic and neighbourhood factors
      on self rated health, quality of life, and perceived opportunities for change (as
      one measure of empowerment) in rural Irish communities. DESIGN: Pooled data from
      cross sectional surveys two years apart. SETTING: Respondents in four randomly
      selected rural district electoral divisions with a population size of between 750
      and 2000. PARTICIPANTS: 1738 rural dwellers aged 15-93, 40.5% men, interviewed at
      two time points. MAIN OUTCOME MEASURES: Determinants of self rated health (SRH),
      quality of life (QOL), and perceived opportunities for change, rated on a closed
      option Likert scale and assessed in multivariate logistic regression models. MAIN
      RESULTS: Overall 23.8% of the sample reported poor SRH, 22.2% poor QOL, and 50.1%
      low perceived opportunities for change. Low financial security and
      dissatisfaction with work were each significantly associated with poor SRH (OR =
      1.96 (1.50 to 2.56) and 1.54 (1.11 to 2.14)), with poor QOL (OR = 2.04 (1.56 to
      2.68) and 1.87 (1.34 to 2.61). Concern about access to public services was
      significantly predictive of SRH (OR = 1.47 (1.11 to 1.94)) rather than access to
      health care (that is, hospital and GP services). There were distinct sex specific
      patterns and a generational effect for educational status in men. Variables
      associated with social networks and social support were less strongly predictive
      of SRH and QOL when economic measures were accounted for. CONCLUSION: Inter
      relations between indicators of health status, wellbeing, and deprivation are not
      well studied in rural communities. Material deprivation has a direct influence on
      both health status and quality of life, although immediate sources of support are
      relatively well preserved.

PMID- 15483306
TI  - Seasonal variation of sudden infant death syndrome in Hawaii.
AB  - OBJECTIVE: To test whether the sudden infant death syndrome (SIDS) rate displays
      the universal winter maximum and summer minimum in Hawaii where there is no
      appreciable seasonal variation of temperature. DESIGN: The null hypothesis is
      tested that there is no seasonal variation of necropsied SIDS in Hawaii. The
      numbers of live births and SIDS cases by month for the years 1979 to 2002 were
      collected and the monthly SIDS distribution is predicted based on the age at
      death distribution. SETTING: The state of Hawaii, located in the midst of the
      Pacific Ocean, has a semi-tropical climate with temperatures fluctuating
      diurnally as 25 +/- 5 degrees C throughout the year. Therefore homes are unheated
      and infants are not excessively swaddled. The Hawaii State Department of Health
      maintains vital statistics of all infant births and deaths. MAIN RESULTS: The
      results reject the null hypothesis of no seasonal variation of SIDS (p = 0.026).
      An explanation for the seasonal effect of the winter maximum and summer minimum
      for Hawaiian SIDS is that it arises from the cycle of the school session and
      summer vacation periods that represent variable intensity of a possible viral
      infection vector. SIDS rates in both Hawaii and the United States increase with
      parity, also indicating a possible role of school age siblings as carriers.
      CONCLUSIONS: The winter peak of the SIDS in Hawaii is support for the hypothesis
      that a low grade viral infection, insufficient by itself to be a visible cause of
      death at necropsy, may be implicated as contributing to SIDS in vulnerable
      infants.

PMID- 15483308
TI  - Environmental perceptions and walking in English adults.
AB  - STUDY OBJECTIVE: To examine the relation between adults' perceptions of the
      social and physical environment and their self reported walking behaviour.
      DESIGN: Cross sectional survey. SETTING: England. PARTICIPANTS: A national sample
      of 4265 adults aged 16-74 years. MAIN OUTCOME MEASURES: Self reported walking
      behaviour was categorised into two dichotomous variables: (a) any reported
      walking in past four weeks, (b) reported walking > or =150 minutes per week in
      the past four weeks. Perceptions of the social environment covered safety of
      walking alone and social support for walking. Perceptions of the physical
      environment covered attractiveness of local area for walking, access to shops,
      leisure centres, parks, cycle paths, and traffic density. MAIN RESULTS: In women,
      perceived safety of walking during the day (OR = 0.53; 95% CI: 0.31 to 0.88), and
      no shop within walking distance (OR = 0.72; 95% CI: 0.52 to 0.99) were associated
      with any reported walking occasions. Perceptions of the environment were not
      related to women walking > or =150 min/week. In men, having a park within walking
      distance was associated with walking > or =150 min/week (OR = 2.22; 95% CI: 1.18
      to 4.35). No other significant associations were found. CONCLUSIONS: Women seem
      to be more concerned about walking for utility and in safety. Men are more likely
      to walk > or =150 min/week if they have access to a local park but their walking
      is not influenced by concerns about safety. Future research should focus on the
      relation between objective measures rather than perceptions of the environment
      and physical activity.

PMID- 15483307
TI  - Neighbourhood environments and mortality in an elderly cohort: results from the
      cardiovascular health study.
AB  - BACKGROUND: It has been postulated that neighbourhood conditions are related to
      the health of the elderly population but longitudinal studies are rare and
      confounding by individual level variables remains a possibility. METHODS: Data
      were obtained from the cardiovascular health study, a population based study of
      adults aged 65 years and older. Census block groups were used as proxies for
      neighbourhoods. A summary score was used to characterise the neighbourhood
      socioeconomic environment. Information on personal socioeconomic indicators,
      cardiovascular disease prevalence, and cardiovascular risk factors was obtained
      from the baseline examination. Proportional hazards regression and propensity
      score matching were used to control for individual level variables. RESULTS: Over
      the eight year follow up there were 1346 deaths among the 5074 participants, of
      which 43% were attributable to cardiovascular disease. Among white participants,
      living in the most disadvantaged neighbourhood group was associated with higher
      rates of cardiovascular death, after adjustment for income, education, and
      occupation (hazard ratio (HR) 1.5, 95% confidence intervals (CI) 1.2 to 1.9). No
      neighbourhood differences were observed for non-cardiovascular deaths. Estimates
      for black participants were 1.3 (95% CI 0.7 to 2.3) for cardiovascular deaths and
      1.4 (95% CI 0.8 to 2.4) for non-cardiovascular deaths, but sample size was small.
      In white participants, associations of neighbourhood characteristics with
      cardiovascular mortality persisted after adjustment for prevalent baseline
      disease and cardiovascular risk factors. The use of propensity score matching led
      to similar results (HR for the lowest compared with the highest neighbourhood
      score group: 1.6 95% CI 1.1 to 2.5, controlling for personal socioeconomic
      indicators). CONCLUSION: Neighbourhood disadvantage is related to rates of
      cardiovascular death in elderly white adults.

PMID- 15483309
TI  - Does rear seat belt use vary according to socioeconomic status?

PMID- 15483310
TI  - Organisational justice and change in justice as predictors of employee health:
      the Whitehall II study.
AB  - OBJECTIVE: Organisational justice has been proposed as a new way to examine the
      impact of psychosocial work environment on employee health. This article studied
      the justice of interpersonal treatment by supervisors (the relational component
      of organisational justice) as a predictor of health. DESIGN: Prospective cohort
      study. Phase 1 (1985-88) measured relational justice, job demands, job control,
      social support at work, effort-reward imbalance, and self rated health.
      Relational justice was assessed again at phase 2 (1989-90) and self rated health
      at phase 2 and phase 3 (1991-93). SETTING: 20 civil service departments
      originally located in London. PARTICIPANTS: 10 308 civil servants (6895 men, 3413
      women) aged 35-55. OUTCOME MEASURE: Self rated health. MAIN RESULTS: Men exposed
      to low justice at phase 1 or adverse change in justice between phase 1 and phase
      2 were at higher risk of poor health at phase 2 and phase 3. A favourable change
      in justice was associated with reduced risk. Adjustment for other stress
      indicators had little effect on results. In women, low justice at phase 1
      predicted poor health at phase 2 and phase 3 before but not after adjustment for
      other stress indicators. Adverse change in justice was associated with worse
      health prospects irrespective of adjustments. CONCLUSIONS: The extent to which
      people are treated with justice in workplaces seems to predict their health
      independently of established stressors at work. Evidence on reduced health risk
      after favourable change in organisational justice implies a promising area for
      health interventions at workplace.

PMID- 15483311
TI  - Longitudinal study of the inception of perimenopause in relation to lifetime
      history of sexual or physical violence.
AB  - STUDY OBJECTIVE: To investigate of the extent to which violence over the life
      course accelerates the onset of perimenopause, as measured by menstrual changes.
      DESIGN: Prospective cohort study. SETTING: Boston, Massachusetts. PARTICIPANTS:
      603 premenopausal women aged 36-45 years at baseline who completed a cross
      sectional survey on childhood and adult violence history. MAIN OUTCOME MEASURE:
      Time to perimenopause, defined as time in months from baseline interview to a
      woman's report of (1) an absolute change of at least seven days in menstrual
      cycle length from baseline or subjective report of menstrual irregularity; (2) a
      change in menstrual flow amount or duration; or (3) cessation of periods for at
      least three months, whichever came first. MAIN RESULTS: Experience of abuse was
      associated with delayed onset of menstrual changes indicative of onset of
      perimenopause. Women reporting childhood or adolescent abuse entered
      perimenopause about 35% slower than women who reported no abuse (IRR(adj) = 0.65,
      95% CI 0.45 to 0.95) after adjusting for age, age at menarche, ever live birth,
      ability to maintain living standard, smoking, BMI, and depression. There was a
      similar association among women who reported first abuse during adulthood
      (IRR(adj) = 0.72, 95% CI 0.28 to 1.80). These findings persisted when the cohort
      was restricted to non-depressed women (childhood/adolescent IRR(adj) = 0.57, 95%
      CI 0.36 to 0.90; adulthood IRR(adj) = 0.63, 95% CI 0.23 to 1.77). CONCLUSIONS:
      This study is the first longitudinal analysis of the timing of perimenopause to
      show an association with a history of physical or sexual abuse. Further study of
      the relation between violence and reproductive aging is needed.

PMID- 15483312
TI  - Gender differences in progression to AIDS and death from HIV seroconversion in a
      cohort of injecting drug users from 1986 to 2001.
AB  - BACKGROUND: Although the consensus is that gender does not influence HIV
      progression, its relevance may depend on the setting. AIM: To study gender
      differences in HIV progression to AIDS and death from 1986 to 2001 in a cohort of
      injecting drug user (IDU) seroconverters in Spain. METHODS: Risk of AIDS and
      death in persons infected for the same length of time were compared through
      Kaplan-Meier, allowing for late entry, and Cox regression adjusting for gender,
      age, and calendar period (before 1992, 1992-1995, 1996-1998, 1999-2001) fitted as
      time dependent covariates. RESULTS: Of 929 IDU, 24.7% were women. Median
      seroconversion year was 1993.3 for men and women. 44% of women and 34% of men
      received antiretroviral therapy. Risk of AIDS was lower in women in univariate
      (hazard ratio (HR) 0.72; 95%CI:0.51 to 1.01) and multivariate analyses (HR 0.73
      95%CI:0.52 to 1.03). A 46% reduction in risk of AIDS for period 1999-2001
      compared with 1992-1995 was seen in both men and women (HR: 0.56 (95%CI:0.36 to
      0.87). As for mortality, women's risk of death was lower univariately (HR 0.67
      95%CI:0.45 to 0.99) although compared with 1992-95, men experienced a 34%
      reduction in mortality during 1999-2001 (HR 0.66 95%CI:0.40 to 1.01), which was
      not statistically significant in women. CONCLUSIONS: HIV progression was lower in
      female IDU before and after 1997 and their uptake of antiretroviral therapy was
      higher than male IDU. The inability to detect a reduction in mortality for women
      during 1999-2001 is probably attributable to lack of power. Differences in
      severity of addiction, drug using patterns, and competing causes of death may
      explain these findings.

PMID- 15483313
TI  - Risk factors for asthma prevalence and chronic respiratory illnesses among
      residents of different neighbourhoods in Buffalo, New York.
AB  - STUDY OBJECTIVE: The aim of this study is to identify risk factors for asthma
      prevalence and chronic respiratory illnesses in Buffalo's neighbourhoods after
      previous studies reported increased levels of asthma among residents on Buffalo's
      west side. DESIGN: Cross sectional surveys. SETTING: Buffalo neighbourhoods along
      a US-Canada border crossing point. SUBJECTS: A systematic random survey of 82% of
      the 2000 targeted households was conducted between January and August 2002. MAIN
      RESULTS: A multivariate logistic regression model shows that the risk of persons
      with asthma and chronic respiratory illnesses is significantly (p< or =0.05) high
      among children and young adults living in Buffalo's west side, newer housing
      units, and of Latino ethnicity. In a separate analysis of the nine risk factors,
      it was observed that location, gender, age, and race were significant risk
      factors even after adjusting for age of housing, pets, moulds, animal trigger,
      and smoking. CONCLUSIONS: These findings confirm the hypothesis that a
      considerable risk of asthma and chronic respiratory illnesses exists particularly
      among Buffalo's west side residents. Further evaluation of these risk factors is
      warranted to determine the severity of asthma and the reasons for such a
      significant disease burden.

PMID- 15483314
TI  - Impact of nursing home deaths on life expectancy calculations in small areas.
AB  - STUDY OBJECTIVE: The drive to tackle health inequalities at the local level has
      increased interest in mortality data for small populations. There is some concern
      that nursing homes may affect measures of mortality for small populations, but
      there has been little in depth analysis of this. DESIGN AND SETTING: Deaths
      between 1997 and 2001 and population figures from the GP register (Exeter)
      database and census 2001 were used to produce life expectancy (LE) figures for
      all electoral wards in West Sussex. The proportion of those dying within each
      ward that had been residents of nursing homes was calculated and the relation
      between these variables and deprivation investigated. RESULTS: There was a
      significant linear relation between nursing home deaths and LE (p<0.0001), which
      explained 36% of variation in LE between wards. Deprivation accounted for around
      35% of the variation in LE (p<0.0001) but was not correlated with nursing home
      deaths (p> or =0.0982). Multiple linear regression shows that over 60% of the
      variation in LE at ward level can be explained by both nursing home deaths and
      deprivation (p<0.0001) and that the two variables explain similar proportions of
      this variation. The relation between LE and nursing home deaths within wards
      grouped by deprivation suggests that the impact of nursing homes is strongest in
      deprived wards. CONCLUSIONS: This finding has important implications for LE
      calculations in small populations. Further investigation is now needed to examine
      the impact of nursing homes in other areas, on other mortality measures, and in
      larger populations.

PMID- 15483315
TI  - Ubiquitin-protein ligases.

PMID- 15483316
TI  - Julia Polak.

PMID- 15483317
TI  - Linking JNK signaling to NF-kappaB: a key to survival.
AB  - In addition to marshalling immune and inflammatory responses, transcription
      factors of the NF-kappaB family control cell survival. This control is crucial to
      a wide range of biological processes, including B and T lymphopoiesis, adaptive
      immunity, oncogenesis and cancer chemoresistance. During an inflammatory
      response, NF-kappaB activation antagonizes apoptosis induced by tumor necrosis
      factor (TNF)-alpha, a protective activity that involves suppression of the Jun N
      terminal kinase (JNK) cascade. This suppression can involve upregulation of the
      Gadd45-family member Gadd45beta/Myd118, which associates with the JNK kinase
      MKK7/JNKK2 and blocks its catalytic activity. Upregulation of XIAP, A20 and
      blockers of reactive oxygen species (ROS) appear to be important additional means
      by which NF-kappaB blunts JNK signaling. These recent findings might open up
      entirely new avenues for therapeutic intervention in chronic inflammatory
      diseases and certain cancers; indeed, the Gadd45beta-MKK7 interaction might be a
      key target for such intervention.

PMID- 15483318
TI  - A functional screen identifies lateral transfer of beta-glucuronidase (gus) from
      bacteria to fungi.
AB  - Lateral gene transfer (LGT) from prokaryotes to microbial eukaryotes is usually
      detected by chance through genome-sequencing projects. Here, we explore a
      different, hypothesis-driven approach. We show that the fitness advantage
      associated with the transferred gene, typically invoked only in retrospect, can
      be used to design a functional screen capable of identifying postulated LGT
      cases. We hypothesized that beta-glucuronidase (gus) genes may be prone to LGT
      from bacteria to fungi (thought to lack gus) because this would enable fungi to
      utilize glucuronides in vertebrate urine as a carbon source. Using an enrichment
      procedure based on a glucose-releasing glucuronide analog (cellobiouronic acid),
      we isolated two gus(+) ascomycete fungi from soils (Penicillium canescens and
      Scopulariopsis sp.). A phylogenetic analysis suggested that their gus genes, as
      well as the gus genes identified in genomic sequences of the ascomycetes
      Aspergillus nidulans and Gibberella zeae, had been introgressed laterally from
      high-GC gram(+) bacteria. Two such bacteria (Arthrobacter spp.), isolated
      together with the gus(+) fungi, appeared to be the descendants of a bacterial
      donor organism from which gus had been transferred to fungi. This scenario was
      independently supported by similar substrate affinities of the encoded beta
      glucuronidases, the absence of introns from fungal gus genes, and the similarity
      between the signal peptide-encoding 5' extensions of some fungal gus genes and
      the Arthrobacter sequences upstream of gus. Differences in the sequences of the
      fungal 5' extensions suggested at least two separate introgression events after
      the divergence of the two main Euascomycete classes. We suggest that deposition
      of glucuronides on soils as a result of the colonization of land by vertebrates
      may have favored LGT of gus from bacteria to fungi in soils.

PMID- 15483319
TI  - Divergence population genetics of chimpanzees.
AB  - The divergence of two subspecies of common chimpanzees (Pan troglodytes
      troglodytes and P. t. verus) and the bonobo (P. paniscus) was studied using a
      recently developed method for analyzing population divergence. Under the
      isolation with migration model, the posterior probability distributions of
      divergence time, migration rates, and effective population sizes were estimated
      for large multilocus DNA sequence data sets drawn from the literature. The bonobo
      and the common chimpanzee are estimated to have diverged approximately 0.86 to
      0.89 MYA, and the divergence of the two common chimpanzee subspecies is estimated
      to have occurred 0.42 MYA. P. t. troglodytes appears to have had a larger
      effective population size (22,400 to 27,900) compared with P. paniscus, P. t.
      verus, and the ancestral populations of these species. No evidence of gene flow
      was found in the comparisons involving P. paniscus; however a clear signal of
      unidirectional gene flow was found from P. t. verus to P. t. troglodytes (2Nm =
      0.51).

PMID- 15483320
TI  - Nonuniform concerted evolution and chloroplast capture: heterogeneity of observed
      introgression patterns in three molecular data partition phylogenies of Asian
      Mitella (saxifragaceae).
AB  - Interspecific hybridization is one of the major factors leading to phylogenetic
      incongruence among loci, but the knowledge is still limited about the potential
      of each locus to introgress between species. By directly sequencing three DNA
      regions: chloroplast DNAs (matK gene and trnL-F noncoding region), the nuclear
      ribosomal external transcribed spacer (ETS) region, and internal transcribed
      spacer (ITS) regions, we construct three phylogenetic trees of Asian species of
      Mitella (Saxifragaceae), a genus of perennials in which natural hybrids are
      commonly observed. Within this genus, there is a significant topological conflict
      between chloroplast and nuclear phylogenies and also between the ETS and the ITS,
      which can be attributed to frequent hybridization within the lineage. Chloroplast
      DNAs show the most extensive introgression pattern, ITS regions show a moderate
      pattern, and the ETS region shows no evidence of introgression. Nonuniform
      concerted evolution best explains the difference in the introgression patterns
      between the ETS region and ITS regions, as the sequence heterogeneity of the ITS
      region within an individual genome is estimated to be twice that of an ETS in
      this lineage. Significant gene conversion patterns between two hybridizing taxa
      were observed in contiguous arrays of cloned ETS-ITS sequences, further
      confirming that only ITS regions have introgressed bidirectionally. The
      relatively slow concerted evolution in the ITS regions probably allows the
      coexistence of multiple alleles within a genome, whereas the strong concerted
      evolution in the ETS region rapidly eliminates heterogeneous alleles derived from
      other species, resulting in species delimitations highly concordant with those
      based on morphology. This finding indicates that the use of multiple molecular
      tools has the potential to reveal detailed organismal evolution processes
      involving interspecific hybridization, as an individual locus varies greatly in
      its potential to introgress between species.

PMID- 15483321
TI  - Excess of amino acid substitutions relative to polymorphism between X-linked
      duplications in Drosophila melanogaster.
AB  - We have obtained sequence polymorphism data from 13 genes belonging to 5 gene
      families in Drosophila melanogaster where the K(a)/K(s) between copies is greater
      than 1. Twelve of these 13 loci are X-linked. In general, there is evidence of
      purifying selection in all families, as inferred both from levels of silent and
      replacement variation and insertion/deletion variation, suggesting that the loci
      are likely functional. Shared polymorphisms indicative of gene conversion between
      paralogs are rare among the X-linked families, in contrast to available data from
      autosomal duplicates. McDonald-Kreitman tests between duplicates reveal an excess
      of amino-acid fixations between copies in the X-linked families, suggesting that
      the divergence between these loci was driven by positive selection. In contrast,
      available data from autosomal duplicates show a deficit of fixations, consistent
      with gene conversion being a strong homogenizing force.

PMID- 15483322
TI  - Non-African origin of a local beneficial mutation in D. melanogaster.
AB  - It is well understood that the out-of-Africa habitat expansion of D. melanogaster
      was associated with the fixation of many beneficial mutations. Nevertheless, it
      is not clear yet whether these beneficial mutations segregated already in Africa
      or originated outside of Africa. In this article, we describe an ongoing
      selective sweep specific to one European population. One microsatellite allele
      has increased in a population from The Netherlands to a frequency of 18%, whereas
      it is virtually absent in 12 other European populations. The selective sweep
      resulted in a genomic region of more than 600 kb that is identical by descent.
      This is probably the first evidence of a beneficial mutation that has arisen
      outside of Africa and has resulted in a selective sweep localized in a population
      from The Netherlands.

PMID- 15483323
TI  - Evidence for archaic Asian ancestry on the human X chromosome.
AB  - The human RRM2P4 pseudogene has a pattern of nucleotide polymorphism that is
      unlike any locus published to date. A gene tree constructed from a 2.4-kb
      fragment of the RRM2P4 locus sequenced in a sample of 41 worldwide humans clearly
      roots in East Asia and has a most-recent common ancestor approximately 2 Myr
      before present. The presence of this basal lineage exclusively in Asia results in
      higher nucleotide diversity among non-Africans than among Africans. A global
      survey of a single-nucleotide polymorphism that is diagnostic for the basal,
      Asian lineage in 570 individuals shows that it occurs at frequencies up to 53% in
      south China, whereas only one of 177 surveyed Africans carries this archaic
      lineage. We suggest that this ancient lineage is a remnant of introgressive
      hybridization between expanding anatomically modern humans emerging from Africa
      and archaic populations in Eurasia.

PMID- 15483324
TI  - A comprehensive analysis of mammalian mitochondrial genome base composition and
      improved phylogenetic methods.
AB  - Phylogenetic analysis of mammalian species using mitochondrial protein genes has
      proved to be problematic in many previous studies. The high mutation rate of
      mitochondrial DNA and unusual base composition of several species has prompted us
      to conduct a detailed study of the composition of 69 mammalian mitochondrial
      genomes. Most major changes in base composition between lineages can be
      attributed to shifts between the proportions of C and T on the L-strand. These
      changes are significant at all codon positions and are shown to affect amino acid
      composition. Correlated changes in the base composition of the RNA loops and
      stems are also observed. Following up from previous studies, we investigate
      changes in the base composition of all 12 H-strand proteins and find that
      variability in proportions of C and T is correlated with location on the genome.
      Variation in base composition across genes and species is known to adversely
      affect the performance of phylogenetic inference methods. We have, therefore,
      developed a customized three-state general time-reversible DNA substitution
      model, implemented in the PHASE phylogenetic inference package, which lumps C and
      T into a composite pyrimidine state. We compare the phylogenetic tree obtained
      using the new three-state model with that obtained using a standard four-state
      model. Results using the three-state model are more congruent with recent studies
      using large sets of nuclear genes and help resolve some of the apparent conflicts
      between studies using nuclear and mitochondrial proteins.

PMID- 15483325
TI  - Evolution of vitamin B6 (pyridoxine) metabolism by gain and loss of genes.
AB  - Vitamin B(6) (VB6) functions as a cofactor of many diverse enzymes in amino acid
      metabolism. Three metabolic pathways for pyridoxal 5'-phosphate (PLP; the active
      form of VB6) are known: the de novo pathway, the salvage pathway, and the fungal
      type pathway. Most unicellular organisms and plants biosynthesize VB6 using one
      or two of these three biosynthetic pathways. However, animals such as insects and
      mammals do not possess any of the pathways and, thus, need to intake VB6 in their
      diet to survive. It is conceivable that breakdowns of these pathways occurred in
      the evolutionary lineages of insects and mammals, and one of the major reasons
      for this would be the loss of pertinent genes. We studied the evolution of VB6
      biosynthesis from the view of the gain and loss of 10 pertinent genes in 122
      species whose genome sequences were completely determined. The results revealed
      that each gene in the pathways was lost more than once in the entire evolutionary
      lineages of the 122 species. We also found the following three points regarding
      the evolution of PLP biosynthesis: (1) the breakdown of the PLP biosynthetic
      pathways occurred independently at least three times in animal lineages, (2) the
      de novo pathway was formed by the generation of pdxB in gamma-proteobacteria, and
      (3) the order of the gene loss in VB6 metabolism was conserved among different
      evolutionary lineages. These results suggest that the evolution of VB6 metabolism
      was subject to gains and frequent losses of related genes in the 122 species
      examined. This dynamic nature of the evolutionary changes must have been
      responsible for the breakdowns of the pathways, resulting in profound
      differentiation of heterotrophy among the species.

PMID- 15483326
TI  - The MinMax Squeeze: guaranteeing a minimal tree for population data.
AB  - We report that for population data, where sequences are very similar to one
      another, it is often possible to use a two-pronged (MinMax Squeeze) approach to
      prove that a tree is the shortest possible under the parsimony criterion. Such
      population data can be in a range where parsimony is a maximum likelihood
      estimator. This is in sharp contrast to the case with species data, where
      sequences are much further apart and the problem of guaranteeing an optimal
      phylogenetic tree is known to be computationally prohibitive for realistic
      numbers of species, irrespective of whether likelihood or parsimony is the
      optimality criterion. The Squeeze uses both an upper bound (the length of the
      shortest tree known) and a lower bound derived from partitions of the columns
      (the length of the shortest tree possible). If the two bounds meet, the shortest
      known tree is thus proven to be a shortest possible tree. The implementation is
      first tested on simulated data sets and then applied to 53 complete human
      mitochondrial genomes. The shortest possible trees for those data have several
      significant improvements from the published tree. Namely, a pair of Australian
      lineages comes deeper in the tree (in agreement with archaeological data), and
      the non-African part of the tree shows greater agreement with the geographical
      distribution of lineages.

PMID- 15483327
TI  - A simple hierarchical approach to modeling distributions of substitution rates.
AB  - Genetic sequence data typically exhibit variability in substitution rates across
      sites. In practice, there is often too little variation to fit a different rate
      for each site in the alignment, but the distribution of rates across sites may
      not be well modeled using simple parametric families. Mixtures of different
      distributions can capture more complex patterns of rate variation, but are often
      parameter-rich and difficult to fit. We present a simple hierarchical model in
      which a baseline rate distribution, such as a gamma distribution, is discretized
      into several categories, the quantiles of which are estimated using a discretized
      beta distribution. Although this approach involves adding only two extra
      parameters to a standard distribution, a wide range of rate distributions can be
      captured. Using simulated data, we demonstrate that a "beta-" model can reproduce
      the moments of the rate distribution more accurately than the distribution used
      to simulate the data, even when the baseline rate distribution is misspecified.
      Using hepatitis C virus and mammalian mitochondrial sequences, we show that a
      beta- model can fit as well or better than a model with multiple discrete rate
      categories, and compares favorably with a model which fits a separate rate
      category to each site. We also demonstrate this discretization scheme in the
      context of codon models specifically aimed at identifying individual sites
      undergoing adaptive or purifying evolution.

PMID- 15483328
TI  - Mitochondrial genomes of Clymenella torquata (Maldanidae) and Riftia pachyptila
      (Siboglinidae): evidence for conserved gene order in annelida.
AB  - Mitochondrial genomes are useful tools for inferring evolutionary history.
      However, many taxa are poorly represented by available data. Thus, to further
      understand the phylogenetic potential of complete mitochondrial genome sequence
      data in Annelida (segmented worms), we examined the complete mitochondrial
      sequence for Clymenella torquata (Maldanidae) and an estimated 80% of the
      sequence of Riftia pachyptila (Siboglinidae). These genomes have remarkably
      similar gene orders to previously published annelid genomes, suggesting that gene
      order is conserved across annelids. This result is interesting, given the high
      variation seen in the closely related Mollusca and Brachiopoda. Phylogenetic
      analyses of DNA sequence, amino acid sequence, and gene order all support the
      recent hypothesis that Sipuncula and Annelida are closely related. Our findings
      suggest that gene order data is of limited utility in annelids but that sequence
      data holds promise. Additionally, these genomes show AT bias (approximately 66%)
      and codon usage biases but have a typical gene complement for bilaterian
      mitochondrial genomes.

PMID- 15483329
TI  - Selenoproteins and the metabolic features of the archaeal ancestor of eukaryotes.
AB  - In all three branches of life, some organisms incorporate the rare amino acid
      selenocysteine. Selenoproteins are relevant to the controversy over the metabolic
      features of the archaeal ancestor of eukaryotes because among archaea, several
      known selenoproteins are involved in methanogenesis and autotrophic growth.
      Although the eukaryotic selenocysteine-specific translation apparatus and at
      least one selenoprotein appear to be of archaeal origin, selenoproteins have not
      been identified among sulfur-metabolizing crenarchaeotes. In this regard, both
      the phylogeny and function of archaeal selenoproteins are consistent with the
      argument that the archaeal ancestor was a methanogen. Selenium, however, is
      abundant in sulfur-rich environments, and some anaerobic bacteria reduce sulfur
      and have selenoproteins similar to those in archaea. As additional archaeal
      sequence data becomes available, it will be important to determine whether
      selenoproteins are present in nonmethanogenic archaea, especially the sulfur
      metabolizing crenarchaeotes.

PMID- 15483330
TI  - Determinants of adaptive evolution at the molecular level: the extended
      complexity hypothesis.
AB  - To explain why informational genes (i.e., those involved in transcription,
      translation, and related processes) are less likely than housekeeping genes to be
      horizontally transferred, Jain and coworkers proposed the complexity hypothesis.
      The underlying idea is that informational genes belong to large, complex systems
      of coevolving genes. Consequently, the likelihood of the successful horizontal
      transfer of a single gene from such an integrated system is expected to be low.
      Here, this hypothesis is extended to explain some of the determinants of the mode
      of evolution of coding sequences. It is proposed that genes belonging to complex
      systems are relatively less likely to be under adaptive evolution. To evaluate
      this "extended complexity hypothesis," 2,428 families and protein domains were
      analyzed. This analysis found that genes whose products are highly connected,
      located in intracellular components, and involved in complex processes and
      functions were more conserved and less likely to be under adaptive evolution than
      are other gene products. The extended complexity hypothesis suggests that both
      the mode and the rate of evolution of a protein are influenced by its gene
      ontology (localization, biological process, and molecular function) and by its
      connectivity.

PMID- 15483331
TI  - Different versions of the Dayhoff rate matrix.
AB  - Many phylogenetic inference methods are based on Markov models of sequence
      evolution. These are usually expressed in terms of a matrix (Q) of instantaneous
      rates of change but some models of amino acid replacement, most notably the PAM
      model of Dayhoff and colleagues, were originally published only in terms of time
      dependent probability matrices (P(t)). Previously published methods for deriving
      Q have used eigen-decomposition of an approximation to P(t). We show that the
      commonly used value of t is too large to ensure convergence of the estimates of
      elements of Q. We describe two simpler alternative methods for deriving Q from
      information such as that published by Dayhoff and colleagues. Neither of these
      methods requires approximation or eigen-decomposition. We identify the methods
      used to derive various different versions of the Dayhoff model in current
      software, perform a comparison of existing and new implementations, and, to
      facilitate agreement among scientists using supposedly identical models,
      recommend that one of the new methods be used as a standard.

PMID- 15483332
TI  - Wayward sisters. Progestin siblings exert opposite effects on monkey hearts.

PMID- 15483333
TI  - Homing in on a hormone.Fat-based molecules divert nematodes from survival mode.

PMID- 15483334
TI  - Nuns and monkeys: investigating the behavior of our oldest old.
AB  - The use of nonhuman primates, particularly rhesus macaques (Macaca mulatta), as
      the best model for human physiological and cognitive aging is broadly accepted.
      Studies employing nonhuman primates to investigate behavioral changes that may
      occur with increasing age, however, are not common mostly because of the
      unavailability of appropriate subjects. Recent longitudinal human studies suggest
      that individual personality might play a large role in aging "successfully" and
      in the retention of high levels of cognition into old age. As a result of the
      demographic trend of increasing numbers of aged monkeys and apes in captivity, an
      opportunity exists to further investigate behavioral aging using the monkey
      model.

PMID- 15483335
TI  - Stem cells expressing homing receptors could be expanded from cryopreserved and
      unselected cord blood.
AB  - We assessed the cytokine combinations that are best for ex vivo expansion of cord
      blood (CB) and the increment for cell numbers of nucleated cells, as well as stem
      cells expressing homing receptors, by an ex vivo expansion of cryopreserved and
      unselected CB. Frozen leukocyte concentrates (LC) from CB were thawed and
      cultured at a concentration of 1 x 10(5)/mL in media supplemented with a
      combination of SCF (20 ng/mL)+TPO (50 ng/mL)+FL (50 ng/mL)+/-IL-6 (20 ng/mL)+/-G
      CSF (20 ng/mL). After culturing for 14 days, the expansion folds of cell numbers
      were as follows: TNC 22.3+/-7.8 approximately 26.3+/-4.9, CFU-GM 4.7+/-5.1
      approximately 11.7+/-2.6, CD34+CD38- cell 214.0+/-251.9 approximately 464.1+/
      566.1, CD34+CXCR4+ cell 4384.5+/-1664.7 approximately 7087.2+/-4669.3, CD34+VLA4+
      cell 1444.3+/-1264.0 approximately 2074.9+/-1537.0, CD34+VLA5+ cell 86.2+/-50.9
      approximately 113.2+/-57.1. These results revealed that the number of stem cells
      expressing homing receptors could be increased by an ex vivo expansion of
      cryopreserved and unselected CB using 3 cytokines (SCF, TPO, FL) only. Further in
      vivo studies regarding the engraftment after expansion of the nucleated cells, as
      well as the stem cells expressing homing receptors will be required.

PMID- 15483336
TI  - Effects of cytokine milieu secreted by BCG-treated dendritic cells on allergen
      specific Th immune response.
AB  - Bacillus Calmette-Guerin (BCG) is reported to suppress Th2 response and asthmatic
      reaction. Dendritic cells (DCs), the major antigen-presenting cells, infections
      with BCG are known to result in inducing various cytokines. Thus, DCs are likely
      to play a role in the effects of BCG on asthma. This study aims at investigating
      that cytokine milieu secreted by BCG-treated DCs directly enhances allergen
      specific Th1 response and/or suppresses Th2 response in allergic asthma. DCs and
      CD3+ T cells were generated from Dermatophagoides farinae-sensitive asthmatics.
      DCs were cultured with and without BCG and subjected to flow cytometric analysis.
      IL-12 and IL-10 were determined from the culture supernatants. Some DCs were
      cocultured with T cells in the presence of D. farinae extracts after adding the
      culture supernatants from BCG-treated DCs, and IL-5 and IFN-gamma were
      determined. BCG-treated DCs enhanced significantly the expressions of CD80, CD86,
      and CD40, and the productions of IL-12 and IL-10. Addition of culture
      supernatants from BCG-treated DCs up-regulated production of IFN-gamma by T cells
      stimulated by DCs and D. farinae extracts (p<0.05), but did not down-regulate
      production of IL-5 (p>0.05). The cytokine milieu secreted by BCG-treated DCs
      directly enhanced allergen-specific Th1 response, although did not suppress Th2
      response.

PMID- 15483337
TI  - Intratumoral injection of 188Re labeled cationic polyethylenimine conjugates: a
      preliminary report.
AB  - 188Re (Rhenium) is easily obtained from an in-house 188W/188Re generator that is
      similar to the current 99Mo/99mTc generator, making it very convenient for
      clinical use. This characteristic makes this radionuclide a promising candidate
      as a therapeutic agent. Polyethylenimine (PEI) is a cationic polymer and has been
      used as a gene delivery vector. Positively charged materials interact with
      cellular blood components, vascular endothelium, and plasma proteins. In this
      study, the authors investigated whether intratumoral injection of 188Re labeled
      transferrin (Tf)-PEI conjugates exert the effect of radionuclide therapy against
      the tumor cells. When the diameters of the Ramos lymphoma (human Burkitt's
      lymphoma) xenografted tumors reached approximately 1 cm, 3 kinds of 188Re bound
      compounds (HYNIC-PEI-Tf, HYNIC-PEI, 188Re perrhenate) were injected directly into
      the tumors. There were increases in the retention of 188Re inside the tumor when
      PEI was incorporated with 188Re compared to the use of free 188Re. The 188Re
      HYNIC-Tf-PEI showed the most retention inside the tumor (retention
      rate=approximately 97%). H&E stain of isolated tumor tissues showed that 188Re
      labeled HYNIC-PEI-Tf caused extensive tumor necrosis. These results support 188Re
      HYNIC-PEI-Tf as being a useful radiopharmaceutical agent to treat tumors when
      delivered by intratumoral injection.

PMID- 15483338
TI  - The usefulness of surface electrocardiogram as a prognostic predictor in children
      with idiopathic dilated cardiomyopathy.
AB  - We investigated the interrelations between surface electrocardiographic changes
      and clinical outcomes in children with idiopathic dilated cardiomyopathy (DCMP).
      33 patients (19 boys, 14 girls) were classified into two groups; group I (15) who
      were in poor clinical status or dead; and group II (18) who showed good clinical
      status. Group I had larger LV dimensions compared to group II (Gr I vs. Gr II;
      LVEDD, 52 +/-11 vs. 42+/-7 (mm); LVESD, 43+/-12 vs. 30+/-5 (mm); p<0.05). QRS
      duration was prolonged in Gr I compared to Gr II and normal (Gr I, 84+/-28; Gr
      II, 66+/-12; normal control, 67+/-9). The QRS duration was correlated with the
      dimensions of left ventricle (LV). Corrected QT and JT interval and dispersions
      of QT in the DCMP group showed a significant difference compared to the normal
      control, however there was no significant difference between Gr I and II. In
      conclusion, QRS duration was correlated with ventricular dimension and clinical
      outcome in children with idiopathic dilated cardiomyopathy. Irrespective of
      increased ventricular inhomogeneity, QT dispersion could not be used to predict
      long-term prognosis.

PMID- 15483339
TI  - Genistein supplementation inhibits atherosclerosis with stabilization of the
      lesions in hypercholesterolemic rabbits.
AB  - The effect of genistein on aortic atherosclerosis was studied by
      immunohistochemistry with RAM-11 and HHF-35 antibodies and western blotting for
      matrix metalloproteinase-3 (MMP-3) in New Zealand White rabbits. After
      provocation of atherosclerosis with hyperlipidemic diet, the rabbits were divided
      as hyperlipidemic diet group (HD), normal diet group (ND) and hyperlipidemic plus
      genistein diet group (HD+genistein) for 4 and half months. The average cross
      sectional area of atherosclerotic lesion was 0.269 mm2 after provocation. The
      lesion was progressed by continuous hyperlipidemic diet (10.06 mm2) but was
      increased mildly by genistein (0.997 mm2), and decreased by normal diet (0.228
      mm2). The ratio of macrophages to smooth muscle cells in the lesion was not
      changed by genistein supplementation. The western blotting showed reduction of
      MMP-3 expression in HD+genistein and ND groups than HD group. The inhibition of
      atherogenesis by genistein was might be due to improve the endothelial
      dysfunction rather than direct action on macrophages and/or smooth muscle cells
      in the lesion, since endothelial dysfunction by lipid peroxidation was the main
      atherogenic factor in the hypercholesterolemic rabbits. The genistein
      supplementation also suggests that it helps the stabilization of the
      atherosclerotic lesion by inhibition of MMP-3 expression.

PMID- 15483340
TI  - Predictive value of Kushida index and acoustic pharyngometry for the evaluation
      of upper airway in subjects with or without obstructive sleep apnea.
AB  - Acoustic pharyngometry is a relatively new noninvasive method that quantifies
      geometrically complexed pharyngeal dimensions. Our study aimed to investigate the
      predictability and usefulness of acoustic pharyngometry in diagnosis of
      obstructive sleep apnea (OSA), and we developed a prospective clinical trial in
      16 subjects without apnea and 54 subjects with apnea. All seventy subjects
      received polysomnography (PSG) to assess the sleep architecture, including
      breathing and the degree of apnea hypopnea index. Acoustic pharyngometry was
      performed in four body positions (sitting, supine, right and left lateral) while
      awake with tidal breathing in addition to morphometric measurements (Kushida
      index) of oral cavity. This study shows that the cross-sectional area and volume
      of the upper airway is smaller in the supine position than any other positions.
      As well, the oropharyngeal junction area of the supine position is the most
      predictive parameter to discriminate between subjects with or without OSA.
      Acoustic pharyngometry can be a clinically useful tool for localizing the
      narrowed portion of the upper airway and predicting obstructive sleep apnea.

PMID- 15483341
TI  - Clinical role of interstitial pneumonia in patients with scrub typhus: a possible
      marker of disease severity.
AB  - Interstitial pneumonia (IP) frequently occurs in patients with scrub typhus, but
      its clinical significance is not well known. This study was designed to evaluate
      interstitial pneumonia as a marker of severity of the disease for patients with
      scrub typhus. We investigated clinical parameters representing the severity of
      the disease, and the chest radiographic findings for 101 patients with scrub
      typhus. We then compared these clinical factors between patients with and without
      IP. We also studied the relationship between IP and other chest radiographic
      findings. The chest radiography showed IP (51.4%), pleural effusion (42.6%),
      cardiomegaly (14.9%), pulmonary alveolar edema (20.8%), hilar lymphadenopathy
      (13.8%) and focal atelectasis (11.8%), respectively. The patients with IP (n=52)
      had higher incidences in episode of hypoxia (p=0.030), hypotension (p=0.024),
      severe thrombocytopenia (p=0.036) and hypoalbuminemia (p=0.013) than the patients
      without IP (n=49). The patients with IP also had higher incidences of pleural
      effusion (p<0.001), focal atelectasis (p=0.019), cardiomegaly (p<0.001),
      pulmonary alveolar edema (p=0.011) and hilar lymphadenopathy (p<0.001) than the
      patients without IP. Our data suggest that IP frequently occurs for patients with
      scrub typhus and its presence is closely associated with the disease severity of
      scrub typhus.

PMID- 15483342
TI  - Pattern of recurrence after curative resection of local (stage I and II) non
      small cell lung cancer: difference according to the histologic type.
AB  - The aim of the present study was to evaluate the pattern of recurrence after
      complete resection of pathological stage I, II non-small cell lung cancer,
      especially according to the cell type. We reviewed the clinical records of 525
      patients operated on for pathologic stage I and II lung cancer. The histologic
      type was found to be squamous in 253 and non-squamous in 229 patients. Median
      follow-up period was 40 months. Recurrences were identified in 173 (36%) of 482
      enrolled patients; distant metastasis in 70%, distant and local recurrence in
      11%, and local recurrence in 19%. Distant metastasis was more common in non
      squamous than in squamous cell carcinoma (p=0.044). Brain metastasis was more
      frequently identified in non-squamous than in squamous cell carcinoma (24.2% vs.
      7.3%. p=0.005). Multivariate analyses showed that cell type is the significant
      risk factor for recurrence-free survival in stage I and stage II non-small cell
      lung cancer. Recurrence-free survival curves showed that non-squamous cell
      carcinoma had similar risks during early periods of follow-up and more risks
      after 2 yr from the operation compared to squamous cell carcinoma. Pathological
      stage and histologic type significantly influence recurrence-free survival.

PMID- 15483343
TI  - Comparison of hospital charge prediction models for colorectal cancer patients:
      neural network vs. decision tree models.
AB  - Analysis and prediction of the care charges related to colorectal cancer in Korea
      are important for the allocation of medical resources and the establishment of
      medical policies because the incidence and the hospital charges for colorectal
      cancer are rapidly increasing. But the previous studies based on statistical
      analysis to predict the hospital charges for patients did not show satisfactory
      results. Recently, data mining emerges as a new technique to extract knowledge
      from the huge and diverse medical data. Thus, we built models using data mining
      techniques to predict hospital charge for the patients. A total of 1,022
      admission records with 154 variables of 492 patients were used to build
      prediction models who had been treated from 1999 to 2002 in the Kyung Hee
      University Hospital. We built an artificial neural network (ANN) model and a
      classification and regression tree (CART) model, and compared their prediction
      accuracy. Linear correlation coefficients were high in both models and the mean
      absolute errors were similar. But ANN models showed a better linear correlation
      than CART model (0.813 vs. 0.713 for the hospital charge paid by insurance and
      0.746 vs. 0.720 for the hospital charge paid by patients). We suggest that ANN
      model has a better performance to predict charges of colorectal cancer patients.

PMID- 15483344
TI  - Genetic alterations in intrahepatic cholangiocarcinoma as revealed by degenerate
      oligonucleotide primed PCR-comparative genomic hybridization.
AB  - Intrahepatic cholangiocarcinoma (ICC), a malignant neoplasm of the biliary
      epithelium,is usually fatal because of difficulty in early diagnosis and lack of
      availability of effective therapy. The genetic mechanisms involved in the
      development of ICC are not well understood and only a few cytogenetic studies of
      ICC have been published. Recently, technique of degenerate oligonucleotide primed
      (DOP)-PCR comparative genomic hybridization (CGH) permits genetic imbalances
      screening of the entire genome using only small amounts of tumor DNA. In this
      study chromosomal aberrations in 33 Korean ICC were investigated by DOP-PCR CGH.
      The common sites of copy number increases were 20q (67%), 17 (61%), 11q11-q13
      (42%), 8p12- qter (39%), 18p (39%), 15q22-qter (36%), 16p (36%), 6p21 (30%), 3q25
      qter (27%), 1q41-qter (24%), and 5p14-q11.2 (24%). DNA amplification was
      identified in 16 carcinomas (48%). The frequent sites of amplification were 20q,
      17p, 17q23-qter, and 7p. The most frequent sites of copy number decreases were
      1p32-pter (21%) and 4q (21%). The recurrent chromosomal aberrations identified in
      this study provide candidate regions involved in the tumorigenesis and
      progression of ICC.

PMID- 15483345
TI  - Maternal serum levels of VCAM-1, ICAM-1 and E-selectin in preeclampsia.
AB  - Endothelial dysfunction is thought to be a central pathogenic feature in
      preeclampsia on the basis of elevated adhesion molecules. The aim of the present
      study was to compare the levels of soluble vascular cell adhesion molecule-1
      (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1) and E-selectin (sE
      selectin) in sera of normal and preeclamptic pregnancies. We studied the serum
      levels of sVCAM-1, sICAM-1 and sE-selectin in normal pregnant women (n=63), mild
      preeclampsia (n=33) and severe preeclampsia (n=82). Concentrations of soluble
      adhesion molecules were determined with enzyme-linked immunoassay (ELISA). Serum
      concentrations of sVCAM-1 were significantly higher in both mild (p=0.004) and
      severe preeclampsia (p=0.000) than normal pregnancy. There were also significant
      differences in sVCAM- 1 levels between mild and severe preeclampsia (p=0.002).
      sICAM-1 levels of severe preeclampsia were statistically different from those of
      normal pregnancy (p=0.038). Levels of sE-selectin were elevated in both mild
      (p=0.011) and severe preeclampsia (p=0.000) compared to normal pregnancy, but no
      statistical difference between the mild and severe preeclampsia (p=0.345). These
      results suggest that all three soluble adhesion molecules are increased in severe
      preeclampsia, and sVCAM-1 among them may be useful in predicting the severity of
      preeclampsia.

PMID- 15483346
TI  - The prognostic effect of VEGF expression in squamous cell carcinoma of the cervix
      treated with radiation therapy alone.
AB  - We investigated the relationship between vascular endothelial growth factor
      (VEGF) expression and clinical outcome in squamous cell carcinoma of the cervix
      treated with radiotherapy alone. The immunohistochemical study was performed for
      forty-two paraffin embedded specimens with anti-VEGF mouse monoclonal antibody.
      Staining was defined as positive for VEGF when more than 10% of the tumor cells
      were stained from 500 cells counted. Positive VEGF expression was observed in
      twenty-one among forty-two patients. VEGF expression according to stage
      (p=0.101), lymph node status (p=0.621), parametrial invasion (p=0.268), and age
      (p=0.5) revealed no significant difference. But the VEGF expression was
      significantly higher in tumors larger than 4 cm (p=0.031). Five year survival
      rates according to VEGF expression status were 89% for VEGF negative group and
      47% for VEGF positive group (p=0.02). FIGO stage (p=0.007), tumor size (p=0.025)
      and the duration of external beam radiation therapy (p=0.006) were also
      significant prognostic factors for overall survival. We suggest that VEGF
      expression may be a prognotic factor of the cervix cancer patients treated with
      radiation therapy alone.

PMID- 15483347
TI  - The role of microsatellite instability at chromosome 11p15.5 in the progression
      of breast ductal carcinoma.
AB  - The study of microsatellite instability (MSI) has provided the evidence to
      support a sequential, progressive pathway for the development of cancer. In this
      study, we analyzed the role of MSI at chromosome 11p15.5 using microdissection of
      paraffin-embedded tissue from 68 matched normal and breast tumor samples.
      Components of intraductal, invasive and metastatic foci in lymph node were
      assessed for MSI using the polymorphic markers D11S922, tyrosine hydroxylase (TH)
      and D11S988. We found that MSI at D11S922 was relatively high incidence than
      other two markers and increased during breast cancer progression. The overall
      frequency of MSI at D11S922 was 26.7% in pure intraductal carcinoma, 36.4% in
      invasive carcinoma, and 40.0% in invasive carcinoma with metastases. We observed
      no significant correlation between MSI at chromosome 11p15.5 and the patient's
      age, tumor size, histological grade, or lymph node metastasis. We compared the
      MSI incidence with the expression of prognostic markers, such as p53, c-erb B2,
      estrogen receptor, and progesterone receptor, and found no significant
      correlation. We suggest that the MSI of chromosome 11p15.5 is increased during
      breast cancer progression, but long-term follow-up study would establish whether
      MSI at chromosome 11p15.5 could be useful as a potential prognostic marker for
      breast cancer.

PMID- 15483348
TI  - Theophylline increases the uptake of radioiodine by mouse thyroid.
AB  - Diagnostic and therapeutic use of radioiodine in the management of thyroid
      disorders depends on the ability of thyroid cells to concentrate radioiodine, a
      process that is regulated by the intracellular increase in cAMP. We hypothesized
      that theophylline, a drug known to increase intracellular cAMP via inhibition of
      phosphodiesterase, could increase thyroidal radioiodine uptake. We tested this
      effect in vivo, using C57BL/6j mice, and in vitro, using Fisher rat thyroid (FRTL
      5) cells. One mouse received 2.5mg theophylline i.p., whereas a control mouse
      received only saline. Twenty-hours after theophylline, mice were injected with 10
      microCi Na125I in 0.1 mL saline through the tail vein. Mean thyroidal 125I
      activity was 3.3-fold higher in theophylline-treated mice than in their
      respective controls. Radioiodine uptake and intracellular cAMP production of FRTL
      5 cells were increased by a relatively low concentration of theophylline (1
      microM). Intracellular cAMP increased up to 30 min and then declined in response
      to 1 microM theophylline. Sera from theophylline-treated mice stimulated 125I
      uptake and intracellular cAMP production by FRTL-5 cells. These findings show
      that theophylline can enhance radioiodine uptake by thyrocytes in vivo and in
      vitro. The in vitro effects of theophylline on both radioiodine uptake and cAMP
      production in a dose-dependent manner are consistent with an action mediated by
      phosphodiesterase inhibition.

PMID- 15483349
TI  - Increased expression of focal adhesion kinase in thyroid cancer:
      immunohistochemical study.
AB  - Focal adhesion kinase (FAK) is a tyrosine kinase that is found in cellular
      structures called focal adhesions. FAK appears to be a key element in signal
      transduction pathways involved in cell adhesion and locomotion. FAK is
      overexpressed in various tumors, including tumors derived from regions of the
      head and neck, colon, breast, prostate, and liver. In this study, we investigated
      immunohistochemically whether FAK expression was increased in thyroid cancers.
      FAK staining was not seen in any of the 20 normal thyroid tissues or the 6
      nodular hyperplasia specimens. In contrast, FAK staining was observed in all of
      17 papillary carcinomas, 9 follicular carcinomas, 8 medullary carcinomas, and 2
      anaplastic carcinomas. Nine of 17 follicular adenomas showed FAK
      immunoreactivity. FAK was not expressed in normal tissue and nodular hyperplasia,
      but was expressed in some of the follicular adenoma, and all of the follicular,
      papillary, medullary and anaplastic thyroid carcinoma. This result indicates that
      the up-regulation of FAK may play a role in the development of thyroid
      carcinogenesis.

PMID- 15483350
TI  - Epidemiological change of atopic dermatitis and food allergy in school-aged
      children in Korea between 1995 and 2000.
AB  - Little is known about the prevalence of atopic dermatitis and food allergy
      outside North America and Europe. We evaluated the prevalence of atopic
      dermatitis and food allergy with the comparison of prevalence between 1995 and
      2000 in Korea and evaluated the correlation of prevalence between atopic
      dermatitis and food allergy. A cross-sectional questionnaire survey was conducted
      on random samples of schoolchildren 6 to 14 yr at two time points, 1995 and 2000
      throughout Korea. The last twelve months prevalence of atopic dermatitis in
      Korean school-aged children was increased from 1995 to 2000. The twelve-month
      prevalence of atopic dermatitis and food allergy were higher in Seoul than in any
      other provincial cities in 1995, but the prevalence of both diseases in Seoul and
      Provincial Centers became to be similar in 2000. The rate responded to food
      allergy of children with atopic dermatitis (9.5%) was lower than that of the
      western countries (60%). And our data demonstrated paternal and maternal allergy
      history is very significantly correlated to developing atopic dermatitis in their
      offspring. The further objective evaluations are required to confirm these
      outcomes because the environmental and risk factors may be different among the
      countries according to their living cultures.

PMID- 15483351
TI  - Increased releasability of skin mast cells after exercise in patients with
      exercise-induced asthma.
AB  - The role of lung mast cells in exercise-induced asthma (EIA) is controversial. To
      investigate whether the skin mast cell releasability is increased after exercise
      in EIA, 49 young atopic men with or without asthma took part in a free-running
      test for 6 min and were given skin prick tests using morphine, a mast cell
      secretagogue, before and after the exercise. The mean diameters of the wheal
      induced by morphine in patients with EIA were not significantly different from
      those in patients without EIA before exercise, although the baseline lung
      function was significantly lower and the airway hyperresponsiveness, the
      peripheral blood eosinophil count, and the size of the wheal in response to
      Dermatophagoides pteronyssinus were significantly higher in patients with EIA.
      However, the differences of the morphine-induced wheal diameter between patients
      with EIA and those without EIA became significant at 120 min after exercise
      (p<0.05), while the responses to histamine were not significantly different.
      These results suggest that exercise increases the releasability of skin mast
      cells in EIA patients whose asthma/allergy are relatively severe.

PMID- 15483352
TI  - Endovascular management of iliofemoral deep venous thrombosis due to iliac vein
      compression syndrome in patients with protein C and/or S deficiency.
AB  - The purpose of this study was to evaluate the early outcome of endovascular
      management in patients with iliofemoral deep venous thrombosis (DVT) due to iliac
      vein compression syndrome (IVCS) and protein C and/or S deficiency. Between
      September 2000 and January 2003, catheter-directed thrombolysis was performed in
      11 patients with a diagnosis of acute iliofemoral DVT: 7 with protein C and/or S
      deficiency and 4 without protein C and/or S deficiency. After thrombolysis, the
      diagnosis of IVCS was confirmed in 6 patients: 4 with protein C and/or S
      deficiency and 2 without protein C and/or S deficiency. Further intervention
      consisted of angioplasty and stent placement was performed. Four patients with
      IVCS and protein C and/or S deficiency were included in this study. The immediate
      technical and clinical success rates were 100% in all 4 patients. There were no
      complications or clinically detectable pulmonary emboli. This initial experience
      suggests that endovascular management of iliofemoral DVT due to IVCS in patients
      with protein C and/or S deficiency is safe and effective.

PMID- 15483353
TI  - Detection rates of bacteria in chronic otitis media with effusion in children.
AB  - This study was performed to investigate polymerase chain reaction-based detection
      of bacterial DNA in middle ear fluid and assess the correlation between the PCR
      positive rate with several factors associated with middle ear effusion. The
      purpose was to gain a further understanding of bacterial infection as a major
      cause of otitis media with effusion. Of the 278 specimens of middle ear fluid, 39
      (14%) tested positive by ordinary culture. The overall detection rate of
      bacterial DNA using the PCR method was 36.7% for middle ear effusion, and
      bacterial DNA detection rates of Hemophilus influenzae, Streptococcus pneumoniae,
      Moraxella catarrhalis in the middle ear effusion were 29.1%, 4.7% and 10.8%,
      respectively. The bacterial DNA detection rate was higher in ears with a history
      of acute otitis media than those without the history. High detection rates were
      observed in patients younger than 48 months who have had a higher tendency to
      present with acute otitis media. We concluded that PCR is a more sensitive method
      for the detection of bacteria in middle ear effusion than ordinary culture, and
      acute otitis media is a major contributor to the pathogenesis of otitis media
      with effusion.

PMID- 15483354
TI  - Clinical diagnostic accuracy of otitis media with effusion in children, and
      significance of myringotomy: diagnostic or therapeutic?
AB  - The specific aims of this prospective survey were to determine the accuracy of
      traditional diagnostic tools, such as pneumatic otoscopy, otomicroscopy, and
      tympanometry, and evaluate the usefulness of myringotomy as a diagnostic method;
      also to determine the significance of myringotomy in treating otitis media with
      effusion (OME). The status of middle ear of 51 children (85 ears) from November
      2002 to February 2003 was examined using pneumatic otoscopy, otomicroscopy, and
      tympanometry, and the presence/absence of middle ear effusion was confirmed by
      myringotomy. The otomicroscopy was the most sensitive and specific one among
      three diagnostic tools. But, it had some false positive cases. This study failed
      to show the therapeutic efficacy of myringotomy. Otomicroscopy seems to have the
      potential to become the standard for diagnosis of OME and for validation of
      pneumatic otoscopy in children. However, when otoscopic, otomicroscopic findings
      and tympanogram of suspected ear show poor correlation, myringotomy can be used
      to confirm the presence of OME, as the diagnostic modality. As the therapeutic
      modality, we think that it is proper to limit indications of myringotomy to some
      selected cases.

PMID- 15483355
TI  - Proton magnetic resonance spectroscopic changes of the primary motor cortex and
      supplementary motor area in hemiparetic patients with corticospinal tract injury
      due to deep intracerebral hematoma.
AB  - This study was conducted to investigate the metabolic changes in the motor and
      motor association cortices following axonal injury in the internal capsule that
      was caused by deep intracerebral hematoma. Using proton magnetic resonance
      spectroscopy (1H MRS), the authors studied the primary motor cortices (M-1) and
      supplementary motor areas (SMA) of 9 hemiparetic patients with documentable
      hemiparesis of varying severity, and we studied 10 normal volunteers as controls.
      To measure the M-1 and SMA biochemical changes, 4 separate single volumes of
      interest (VOIs) were located bilaterally in the affected and unaffected
      hemisphere (AH and UH). 1H MRS provided a neuronal and axonal viability index by
      measuring levels of N-acetylaspartate (NAA) and creatine/phosphocreatine (Cr).
      The M-1/SMA NAA/Cr ratios of the AH and UH in patients, and the AH and normal
      volunteers were compared. The NAA/Cr ratios of the M-1 and SMA in AH, and the SMA
      in UH were significantly lower than those of normal volunteers. These 1H MRS
      findings indicate that axonal injury in the descending motor pathway at the level
      of internal capsule could induce metabolic changes in the higher centers of the
      motor pathway.

PMID- 15483356
TI  - A case report of a poor metabolizer of CYP2D6 presented with unusual responses to
      nortriptyline medication.
AB  - We present a case with decreased metabolic activity of CYP2D6, a cytochrome P450
      enzyme catalyzing the metabolism of nortriptyline (NT). Conventional dosage
      regimen led to toxic plasma concentration of NT and adverse effects such as dry
      mouth, constipation, and dizziness in this case with genotype CYP2D6*5/*10B. This
      case suggests the clinical usefulness of pharmacogenetic testing in
      individualized dosage adjustments of NT.

PMID- 15483357
TI  - A case of Lambert-Eaton myasthenic syndrome associated with atypical
      bronchopulmonary carcinoid tumor.
AB  - The Lambert-Eaton myasthenic syndrome (LEMS) is typically recognized as a
      paraneoplastic syndrome associated with a small cell lung carcinoma (SCLC),
      whereas LEMS with other neuroendocrine lung tumors, including carcinoids or large
      cell lung carcinoma, are highly unusual. Here, we report a rare case of LEMS with
      atypical bronchopulmonary carcinoid tumor: a 65-yr-old man presented with
      progressive leg weakness and a diagnosis of LEMS was made by serial repetitive
      nerve stimulation test. Chest CT revealed a lung nodule with enlargement of
      paratracheal lymph nodes, and surgically resected lesion showed pathological
      features of atypical carcinoid tumor. We concluded that LEMS could be associated
      with rare pulmonary neuroendocrine tumor other than SCLC, which necessitates
      pathologic confirmation followed by aggressive treatment for optimal management
      in these rare cases.

PMID- 15483358
TI  - Subcutaneous emphysema mimicking gas gangrene following perforation of the
      rectum: a case report.
AB  - We report a case of extensive subcutaneous emphysema of the lower extremity
      mimicking gas gangrene following perforation of the rectum in a 38-yr-old man.
      Subcutaneous emphysema of the leg may rarely occur secondary to perforation of
      the gastrointestinal tract and has often created serious diagnostic problems and
      high mortality rates. Therefore, prompt diagnosis and aggressive treatment is
      imperative.

PMID- 15483359
TI  - Imaging findings of hepatic paragonimiasis : a case report.
AB  - Hepatic paragonimiasis is a rare form of ectopic infestation caused by
      Paragonimus. We experienced a case of hepatic paragonimiasis that showed
      characteristic imaging findings. CT and MR images showed a cluster of small cysts
      with rim enhancement in the subcapsular area of the liver. This finding seems to
      be characteristic for hepatic paragonimiasis, considering imaging findings in
      paragonimiasis involving other organs.

PMID- 15483360
TI  - Malignant gastrointestinal stromal tumor of the gallbladder.
AB  - Gastrointestinal stromal tumors (GISTs) of the gallbladder are representative of
      an extremely rare group of tumors. We have encountered a patient with a malignant
      GIST of the gallbladder and presented it with a review of some articles. A 72-yr
      old woman initially presented with right upper quadrant abdominal pain, fever and
      chills. Emergency cholecystectomy was performed under the impression of
      gallbladder empyema. Liver metastasis was found at 7 months postoperatively and
      the patient expired 9 months after the surgery. At the time of cholecystectomy,
      the gallbladder showed a necrotic serosal surface with an irregular thickened
      wall. A mass, 6 cm in length and 3 cm in width, encircled the whole wall of the
      neck and upper body of the gallbladder. Microscopic findings revealed frequent
      mitotic figures (more than 20/50 HPF) and tumor necrosis. Hyperchromatic,
      pleomorphic and spindle shaped neoplastic cells that were arranged in a pattern
      of short fascicles infiltrated the entire layer of the gallbladder. The tumor
      cells were immunoreactive for CD117 antigen (c-kit protein) and vimentin. They
      were negative for desmin, smooth muscle actin and S-100 protein. Mutations of the
      c-kit proto-oncogene were not found in this case. These findings were sufficient
      to provide enough clinical, histopathological and immunohistochemical evidence in
      diagnosing our case as a malignant GIST.

PMID- 15483361
TI  - A Korean case of juvenile muscular atrophy of distal upper extremity (Hirayama
      disease) with dynamic cervical cord compression.
AB  - We present a Korean case of Hirayama disease with its typical neuroradiological
      findings of forward displacement of cervical dural sac and compression of the
      lower cervical cord during neck flexion. A 15-yr-old boy was presented with a one
      year history of progressive weakness and atrophy affecting bilateral hands and
      forearms. The electrodiagnostic findings were compatible with the lesion of the
      anterior horn cells at the C7, C8, and T1 spinal segments. With neck flexion,
      cervical magnetic resonance imaging (MRI) showed the anterior shifting of the
      lower cervical dural sac resulting in the cord compression of those segments.
      Presumably, this disease might have been prevalent in Korea frequently under the
      diagnosis of "benign focal amyotrophy". In this regard, we discuss the clinical
      importance of cervical MRI with neck flexion and anticipate the increasing
      reports of the case substantiated by its characteristic radiological features.

PMID- 15483362
TI  - Astroblastoma: a case report.
AB  - Astroblastoma is one of the very unusual type of tumors, whose histogenesis has
      not been clarified. It occurs mainly among children or young adults.
      Astroblastoma is grossly well-demarcated, and shows histologically characteristic
      perivascular pseudorosettes with frequent vascular hyalinization. Perivascular
      pseudorosettes in astroblastoma have short and thick cytoplasmic processes and
      blunt-ended foot plates. A 15-yr-old girl presented with headache and diplopia
      for one and a half year. A well-demarcated mass, 9.7 cm in diameter, was found in
      the right frontal lobe in brain MRI, and it was a well-enhanced inhomogenous
      mass. Cystic changes of various sizes were observed inside the tumor mass as well
      as in the posterior part of the mass, but no peritumoral edema was found.
      Histologically, this mass belongs to a typical astroblastoma, and no sign of
      anaplastic astrocytoma, gemistocytic astrocytoma or glioblastoma was found in any
      part of the tumor. Immunohistochemically, the tumor cells showed diffuse strong
      positivity for glial fibrillary acidic protein, S-100 protein, vimentin and
      neuron specific enolase, and focal positivity for epithelial membrane antigen and
      CAM 5.2, while showing negativity for synaptophysin, neurofilament protein, pan
      cytokeratin and high molecular weight keratin.

PMID- 15483364
TI  - The first case of intraperitoneal bronchogenic cyst in Korea.

PMID- 15483366
TI  - Acute hyperventilation syndromes induced by sexual intercourse: evidence of a
      psychophysical mechanism to intensify sexual experience?

PMID- 15483367
TI  - Turning on and turning off: a focus group study of the factors that affect
      women's sexual arousal.
AB  - The aim of this study was to inform the development of a questionnaire to assess
      a woman's tendency to respond with sexual excitation/inhibition in different
      situations. Nine focus groups, involving 80 women (M age = 34.3 years; range, 18
      84), were conducted. Women described a wide range of physical (genital and
      nongenital), cognitive/emotional, and behavioral cues to arousal. The
      relationship between sexual interest (desire) and sexual arousal was complex;
      sexual interest was reported as sometimes preceding arousal, but at other times
      following it. Many women did not clearly differentiate between arousal and
      interest. Qualitative data on the factors that women perceived as "enhancers" and
      "inhibitors" of sexual arousal are presented, with a focus on the following
      themes: feelings about one's body; concern about reputation; unwanted
      pregnancy/contraception; feeling desired versus feeling used by a partner;
      feeling accepted by a partner; style of approach/initiation; and negative mood.
      The findings can help inform conceptualizations of sexual arousal in women.

PMID- 15483368
TI  - Lifetime depression history and sexual function in women at midlife.
AB  - We examined the association between lifetime depression history and sexual
      function in a community-based sample of midlife women. Specifically, 914 women
      aged 42-52 who were participants in the Study of Women's Health Across the Nation
      completed a self-report assessment of their sexual behaviors, sexual desire,
      sexual arousal, and sexual satisfaction over the past 6 months. On the basis of
      the Structured Clinical Interview for the DSM-IV , participants were categorized
      into 1 of 3 lifetime major depressive disorder (MDD) history groups: no MDD
      history, single episode MDD, and recurrent MDD. In line with previous reports,
      women with a history of recurrent MDD reported experiencing less frequent sexual
      arousal, less physical pleasure, and less emotional satisfaction within their
      current sexual relationships. Although the groups did not differ in their
      reported frequency of sexual desire or partnered sexual behaviors, lifetime
      depression history was associated with increased rates of self-stimulation
      (masturbation). Associations between lifetime depression history and lower levels
      of physical pleasure within partnered sexual relationships and higher rates of
      masturbation remained significant following control for current depressive
      symptoms, study site, marital status, psychotropic medication use, and lifetime
      history of anxiety or substance abuse/dependence disorder. Future research is
      needed to characterize the temporal and etiologic relationships among lifetime
      depressive disorder, current mood state, and sexual function in women across the
      lifespan.

PMID- 15483369
TI  - Increasing neutral distraction inhibits genital but not subjective sexual arousal
      of sexually functional and dysfunctional men.
AB  - To assess the effects of distraction and level of erotic stimulation on
      physiological and subjective sexual arousal, sexually dysfunctional (n = 23) and
      functional (n = 26) men were studied. It was hypothesized from previous
      investigations that men with erectile dysfunction would show a different genital
      response pattern to distraction during sexual stimulation when compared with
      sexually functional men. Distraction load was manipulated through different
      verbal instructions about how to deal with pairs of random digits. Erotic
      stimulation level was manipulated through the selection of erotic video content.
      In both groups, increasing distraction was found to increasingly inhibit genital
      responding, but not to affect subjective arousal. Both physiological and
      subjective arousal were higher when erotic stimulation level was high. An
      interaction effect of distraction and erotic stimulation level was observed: the
      linear dose-response association that was found during high erotic stimulation
      was not found under low stimulation conditions, which may reflect a floor effect.
      The implications of the findings for the cognitive theory of sexual arousal
      disorder are discussed.

PMID- 15483370
TI  - Attributions for sexual situations in men with and without erectile disorder:
      evidence from a sex-specific attributional style measure.
AB  - This study investigated the attributional styles of men with and without sexual
      dysfunction for both positive and negative sexual and general events using a sex
      specific version of the Attributional Style Questionnaire (Sex-ASQ), and
      ascertained the preliminary psychometric properties of the measure. The Sex-ASQ
      was created by embedding 8 hypothetical sexual events (4 positive, 4 negative)
      among the original 12 events in the Attributional Style Questionnaire (ASQ; C.
      Peterson, A. Semmel, C. von Baeyer, L. Y. Abramson, G. I. Metalsky, & M. E.
      Seligman, 1982). The Sex-ASQ was completed by 21 men with a principal DSM-IV
      diagnosis of Male Erectile Disorder (MED) and 32 male control participants. The
      psychometrics of the Sex-ASQ were satisfactory, but with the positive sexual
      event scales found to be less stable and internally consistent than the negative
      sexual event scales. Reasons for modest reliability of the positive event scales
      are discussed in terms of the original ASQ. As expected, men with MED did not
      differ significantly from men without sexual dysfunction in their causal
      attributions for general events, indicating that both groups exhibited an
      optimistic attributional style in general. Also as predicted, men with MED made
      more internal and stable causal attributions for negative sexual events than men
      without sexual dysfunction, and also rated negative sexual events as more
      important. For positive sexual events, the 2 groups did not differ in
      attributional style, with both groups making more external/unstable/specific
      causal attributions than for positive general events. Differences between
      explanatory style for sexual versus nonsexual events found in both sexually
      functional and dysfunctional men lend support for explanatory style models that
      propose both cross-situational consistency and situational specificity.

PMID- 15483372
TI  - Sex with men before coming-out: relation to sexual activity and sexual risk
      taking behavior.
AB  - This study examined the difference in sequence of coming-out and first same-sex
      experience in relation to risk-taking behavior in a sample of Dutch gay and
      bisexual men. A questionnaire assessed age of disclosure (coming-out) and age of
      first same-sex experience, and information on sexual history, sexual
      relationships, and sexual behavior. It was found that 68% of respondents engaged
      in their first same-sex experience before coming-out. This proportion increased
      with age. Men who had sex with men before coming-out reported more lifetime sex
      partners and more casual sex partners in the past 6 months than men in which this
      sequence was reversed. In addition, among this group a higher proportion of men
      reported STDs, engaging in anal intercourse with casual partners in the previous
      6 months, and unprotected anal sex with casual sex partners in the recent past,
      compared to men who came out before having their first same-sex experience. The
      extent to which external factors (such as tolerance toward homosexuals) or
      internal factors (such as personality factors) can account for the difference in
      sexual behaviors in general and sexual risk-taking behavior in particular could
      be subject of further study.

PMID- 15483371
TI  - The relationship between alcohol and individual differences variables on
      attitudes and behavioral skills relevant to sexual health among heterosexual
      young adult men.
AB  - The purpose of this experiment was to investigate the effects of alcohol, alcohol
      sex expectancies, and sexual sensation seeking on determinants of sexual health
      behavior according to the Information-Motivation-Behavioral Skills (IMB) model.
      The participants were 48 heterosexual young adult males who attended 2 laboratory
      sessions. During Session 1, participants completed a set of screening and
      individual differences measures, and during Session 2 they were randomly assigned
      to 1 of 3 beverage conditions: control, alcohol (0.65 g alcohol/kg body weight),
      or placebo. Following the experimental manipulation, all participants completed
      measures regarding attitudes toward condom use, intention to engage in risky sex,
      and condom use negotiation skills. The results showed that participants who
      consumed alcohol had poorer negotiation skills and greater intention to engage in
      risky sex compared to participants who did not drink alcohol. Although alcohol
      did not affect any dimension of attitude regarding condom use, attitude about
      condoms' effects on sex, as well as sexual sensation seeking, were correlated
      with both intention ratings and skills. Multiple regression models, including
      both attitudes and sensation seeking, showed that attitudes accounted for 20-25%
      of variance independent of beverage condition in predicting intention ratings and
      skills. The findings were consistent with past research showing that alcohol
      consumption can have detrimental effects on determinants of sexual health
      behavior and that individual differences factors can enhance the power of models
      like the IMB to predict such behavior.

PMID- 15483373
TI  - Exacerbation of symptoms among people with multiple sclerosis: impact on
      sexuality and relationships over time.
AB  - This study was designed to evaluate the impact of an exacerbation in symptoms
      among men and women with multiple sclerosis (MS) on sexuality and relationship
      satisfaction. A total of 321 people with MS (120 men, M age = 48.10 years; 201
      women, M age = 45.78 years), and 239 people from the general population (79 men,
      M age = 53.93 years; 160 women, M age = 45.89 years) completed measures of
      relationship satisfaction and sexuality, and then completed these measures again
      18 months later. The results demonstrated that both men and women with MS
      reported significantly higher levels of sexual dysfunction than did the general
      population. The no exacerbation group also reported significantly lower levels of
      sexual activity and of relationship satisfaction than the general population
      group over the 18-month period. Women in all groups reported significantly higher
      levels of sexual dysfunction but also higher levels of sexual activity than did
      men at each time period. They also reported significantly higher levels of sexual
      satisfaction at the 18-month follow up. These results suggest that men and women
      respond in similar ways to MS, and that people with MS do not necessarily
      experience poorer levels of sexual interaction or relationship quality when they
      experience an increase in their physical symptoms.

PMID- 15483375
TI  - Studies of the carbohydrate-carbohydrate interaction between lactose and GM(3)
      using Langmuir monolayers and glycolipid micelles.
AB  - This paper describes studies of the carbohydrate-carbohydrate interaction (CCI)
      between micelles of a lactosyl lipid and monolayers of the glycosphingolipid
      GM(3). The lactose Lac.GM(3) interaction is involved in B16 melanoma cell
      adhesion and signaling processes, and a thorough understanding of the molecular
      details of this CCI is important for the design of new anti-adhesive and anti
      metastatic agents. In this paper, we examine the influence of variations in
      divalent cations and subphase ionic strength on the Lac.GM(3) interaction. Our
      results indicate that, in the absence of divalent cations, the Lac.GM(3) CCI is
      strengthened at higher sodium chloride concentrations in the subphase. In
      contrast, when divalent cations are present in solution, the CCI is not as
      sensitive to ionic strength. These results suggest a role for both cation
      dependent as well as independent interactions in the Lac.GM(3) CCI.

PMID- 15483376
TI  - A glycosynapse in myelin?
AB  - Myelin, the multilayered membrane which surrounds nerve axons, is the only
      example of a membranous structure where contact between extracellular surfaces of
      membrane from the same cell occurs. The two major glycosphingolipids (GSLs) of
      myelin, galactosylceramide (GalC) and its sulfated form, galactosylceramide I(3)
      sulfate (SGC), can interact with each other by trans carbohydrate-carbohydrate
      interactions across apposed membranes. They occur in detergent-insoluble lipid
      rafts containing kinases and thus may be located in membrane signaling domains.
      These signaling domains may contact each other across apposed extracellular
      membranes, thus forming glycosynapses in myelin. Multivalent forms of these
      carbohydrates, GalC/SGC-containing liposomes, or galactose conjugated to albumin,
      have been added to cultured oligodendrocytes (OLs) to mimic interactions which
      might occur between these signaling domains when OL membranes or the
      extracellular surfaces of myelin come into contact. These interactions between
      multivalent carbohydrate and the OL membrane cause co-clustering or
      redistribution of myelin GSLs, GPI-linked proteins, several transmembrane
      proteins, and signaling proteins to the same membrane domains. They also cause
      depolymerization of the cytoskeleton, indicating that they cause transmission of
      a signal across the membrane. Their effects have similarities to those of anti
      GSL antibodies on OLs, shown by others, suggesting that the multivalent
      carbohydrate interacts with GalC/SGC in the OL membrane. Communication between
      the myelin sheath and the axon regulates both axonal and myelin function and is
      necessary to prevent neurodegeneration. Participation of transient GalC and SGC
      interactions in glycosynapses between the apposed extracellular surfaces of
      mature compact internodal myelin might allow transmission of signals throughout
      the myelin sheath and thus facilitate myelin-axonal communication.

PMID- 15483377
TI  - Carbohydrate-carbohydrate interaction as a major force initiating cell-cell
      recognition.
AB  - Sponges were the earliest multicellular organisms to evolve through the
      development of cell recognition and adhesion processes mediated by cell surface
      proteoglycans. Information on sponges has an extra added value because, as a
      group, they are the oldest Metazoans alive and contribute more to our
      understanding of life on earth than knowledge of other animal groups. Although
      the proteoglycans are emerging as key players in various physiological and
      pathophysiological cellular events, little is known about the carbohydrate moiety
      of the proteoglycan molecule. Until recently there was no evidence provided for
      the existence of specific and biologically significant carbohydrate-carbohydrate
      interaction. We show here that the interaction between single oligosaccharides of
      surface proteoglycans is relatively strong (in the 200-300 piconewtons range) and
      in the same range as other relevant biological interactions, like those between
      antibodies and antigens. This carbohydrate-carbohydrate recognition is highly
      species-specific and perfectly mimics specific cell-cell recognition. Both the
      strength and the species-specificity of the carbohydrate-carbohydrate interaction
      are guaranteed by polyvalency, by compositional and architectural differences
      between carbohydrates, and by the arrangement of the carbohydrate chain in a
      three-dimensional context. Ca(2+)-ions are essential and probably provide
      coordinating forces. Our findings confirm the existence and character of species
      specific carbohydrate-carbohydrate recognition fundamental to cell recognition
      and adhesion events.

PMID- 15483378
TI  - Carbohydrate-to-carbohydrate interaction, through glycosynapse, as a basis of
      cell recognition and membrane organization.
AB  - Cell adhesion mediated by carbohydrate-to-carbohydrate interaction (CCI), or cell
      adhesion with concurrent signal transduction, are discussed in three contexts.1.
      Types of cell adhesion based on interaction of several combinations of
      glycosphingolipids (GSLs) at the surface of interfacing cells (" trans
      interactio") are reviewed critically, to exclude the possible involvement of GSL
      binding proteins. Special emphasis is on: (i) autoaggregation of mouse
      teratocarcinoma F9 cells mediated by Le( x )-to-Le( x ) interaction, in which
      presence of Le( x )-binding protein is ruled out; (ii) adhesion of GM3-expressing
      cells to Gg3-expressing cells, in which involvement of GM3- or Gg3-binding
      protein is ruled out.2. Characteristic features and requirements of CCI, as
      compared with carbohydrate-to-protein interaction (CPI) and protein-to-protein
      interaction (PPI), are summarized, including: (i) specificity and requirement of
      bivalent cation; (ii) reaction velocity of CCI as compared to PPI; (iii) negative
      (repulsive) interaction; (iv) synergistic or cooperative effect of CCI and PPI,
      particularly GM3-to-Gg3 or GM3-to-LacCer interaction in synergy with integrin
      dependent adhesion, or Le( x )-to-Le( x ) interaction in cooperation with E
      cadherin-dependent adhesion.3. Microdomains at the cell surface are formed based
      on clustering of GSLs or glycoproteins organized with signal transducers. Among
      such microdomains, those involved in adhesion coupled with signal transduction to
      alter cellular phenotype are termed "glycosynaps". In some glycosynapses, growth
      factor receptors or integrin receptors are also involved, and their function is
      modulated by GSLs only when the receptor is N -glycosylated. This modulation may
      occur in part via interaction of GSLs with N -linked glycans of the receptor,
      termed " cis interactio".

PMID- 15483379
TI  - Analysis of GM3-Gg3 interaction using clustered gycoconjugate models constructed
      from glycolipid monolayers and artificial glycoconjugate polymers.
AB  - Carbohydrate-carbohydrate interactions between clustered GM3 on the Langmuir
      monolayer and clustered Gg3 trisaccharide along a polystyrene chain were
      investigated using surface pressure-area (pi-A) isotherms and surface plasmon
      resonance (SPR). The pi-A isotherm of the GM3 monolayer was expanded
      substantially and specifically by the Gg3-trisaccharide-bearing glycoconjugate
      polystyrene [PN(Gg3)] even at 10(-12) M. The PN(Gg3)-induced expansion of the GM3
      monolayer required no calcium ion, and the expansion was strongly inhibited in
      the presence of urea and acetamido sugars. SPR studies of the GM3-Gg3 interaction
      were carried out to estimate the affinity constant and specificity of the
      interaction quantitatively. PN(Gg3) was adsorbed onto the GM3 monolayer strongly
      and specifically with an apparent affinity constant of Ka = 2.5 x 10(6) M(-1).
      The mechanism of the GM3-Gg3 interaction was discussed on the basis of the
      relationship between affinity and structure. We found that the NHAc groups of N 
      acetylneuraminic acid in GM3 and of GalNAc in Gg3 play an important role in the
      GM3-Gg3 interaction and that PN(Gg3) recognizes not only some specified portions
      of GM3 but also the trisaccharide as a whole. Published in 2003.

PMID- 15483380
TI  - Understanding carbohydrate-carbohydrate interactions by means of
      glyconanotechnology.
AB  - Carbohydrate-carbohydrate interaction is a reliable and versatile mechanism for
      cell adhesion and recognition. Glycosphingolipid (GSL) clusters at the cell
      membrane are mainly involved in this interaction. To investigate carbohydrate
      carbohydrate interaction an integrated strategy (Glyconanotechnology) was
      developed. This strategy includes polyvalent tools (gold glyconanoparticles)
      mimicking GSL clustering at the cell membrane as well as analytical techniques
      such as AFM, TEM, and SPR to evaluate the interactions. The results obtained by
      means of this strategy and current status are presented.

PMID- 15483381
TI  - Specific and non specific interactions involving Le( X ) determinant quantified
      by lipid vesicle micromanipulation.
AB  - Carbohydrate-carbohydrate recognition is emerging today as an important type of
      interaction in cell adhesion. One Ca(2+)mediated homotypic interaction between
      two Lewis( X ) determinants (Le( X )) has been proposed to drive cell adhesion in
      murine embryogenesis. Here, the adhesion energies of lipid vesicles
      functionalized with glycolipids bearing monomeric or dimeric Le( X ) determinants
      were measured in NaCl or CaCl(2) media with the micropipette aspiration
      technique. These experiments on Le( X ) with an environment akin to that provided
      by biological membrane confirmed the existence of this specific calcium dependent
      interaction of monomeric Le( X ). In contrast, dimeric Le( X ) produced a
      repulsive contribution. By using a simple model involving the various
      contributions to the adhesion free energy, specific and non specific interactions
      could be separated and quantified. The involvement of calcium ions has been
      discussed in the monomeric and dimeric Le( X ) lipids.

PMID- 15483382
TI  - Transformation of 2-aminoacetophenone to ( S) -2-amino-1-phenylethanol by
      Arthrobacter sulfureus.
AB  - A new isolate of Arthrobacter sulfureus , when incubated at 50 g resting cells
      (dry cell wt) l(-1) with 50 g glucose l(-1) and 1 g 2-aminoacetophenone l(-1) in
      50 mm potassium buffer (pH 7, 4 ml) at 30 degrees C, produced ( S )-2-amino-1
      phenylethanol (e.e. >99%) with 75% yield in 6 h.

PMID- 15483383
TI  - Enzymatic transesterification of purine nucleoside having a low solubility in
      organic medium.
AB  - Enzymatic transesterification of guanosine having low solubility against organic
      solvent was examined. For the transesterification between guanosine and divinyl
      adipate catalyzed by alkaline protease from Bacillus (Bioprase), DMSO was added
      to DMF to increase the solublility of the nucleoside, and the conversion rate of
      guanosine to the vinyl guanosine ester was less than 30%. To overcome the
      reversible inactivation of enzyme by hydrophilic organic solvents, the reaction
      was carried out with 10% (v/v) water. The transesterification reaction was
      effectively catalyzed in DMF/DMSO in the presence of water and the conversion
      rate increased ca. 70% after 7 d reaction. The result shows that the water effect
      of Bioprase would be a useful method for the synthesis of low solublility
      nucleoside esters.

PMID- 15483384
TI  - Fractionation of the naringinase complex from Aspergillus terreus by dye affinity
      chromatography.
AB  - Affinity chromatography with immobilised triazine dyes was used to separate the
      main enzymes present in the naringinase complex produced by Aspergillus terreus
      CECT 2663. One alpha-L-rhamnosidase and two beta-D-glucosidases (beta G1 and beta
      G2) were separated by a simple two-step procedure involving chromatography with
      Red HE-3B immobilised on Sepharose 4B first at pH 5.5 and then at pH 4.7. Maximum
      activity of the beta-D-glucosidases was from pH 4 to 6 and at 65 degrees C. Both
      glucosidases were active on p -nitrophenol glucoside and prunin with respective
      Km values of 1.9 mm and 1.6 mm for beta G1 and 2.1 mm and 0.25 mm for beta G2.
      Only beta G1 hydrolysed cellobiose (Km = 5.7 mm).

PMID- 15483385
TI  - Improving the expression of mini-proinsulin in Pichia pastoris.
AB  - Increased expression of recombinant mini-proinsulin in Pichia pastoris in 2.5 l
      bioreactors was achieved by increasing the cultivation pH from 5.1 to 6.3, by
      decreasing the temperature from 28 to 22 degrees C, and by periodical addition of
      ammonium sulfate and EDTA to the culture broth. Using this procedure, mini
      proinsulin reached nearly 0.3 g l(-1) in the culture supernatant after 160 h of
      growth.

PMID- 15483386
TI  - Coupled-enzyme system for the determination of lipase activity.
AB  - A new method for lipase activity determination is described, in which liberation
      of fatty acids by lipase-catalyzed hydrolysis is coupled to lipoxygenation. The
      second reaction forms hydroperoxy-fatty acids containing a conjugated double bond
      that are detected at 234 nm. The method is sensitive, cheap and easy to use when
      compared to a titration method.

PMID- 15483387
TI  - Detection of foot-and-mouth virus antibodies using a purified protein from the
      high-level expression of codon-optimized, foot-and-mouth disease virus complex
      epitopes in Escherichia coli.
AB  - A codon optimized DNA sequence coding for foot-and-mouth disease virus (FMDV)
      capsid protein complex epitopes of VP1 amino acid residues 21-40, 135-160, and
      200-213 was genetically fused to the C-terminal end of a glutathione-S
      transferase (GST) gene in pGEX-6P-1 vector with the synonymous codons preferred
      by Escherichia coli . The gene was synthesized using PCR and subsequently
      expressed in E. coli producing an intracellular, soluble fusion protein that
      retained antigenicity associated with FMDV antibodies by western blot analysis.
      The chimera was purified from bacterial lysates by affinity chromatography and
      could be used in ELISA tests for antibodies against FMDV.

PMID- 15483388
TI  - Purification and characterization of a low molecular weight endoxylanase from
      solid-state cultures of alkali-tolerant Aspergillus fischeri.
AB  - A low molecular weight, alkaline-stable endoxylanase (XylB) was purified to
      homogeneity from solid-state culture of Aspergillus fischeri Fxn1. XylB had a
      molecular mass of 13 kDa which is the lowest of reported xylanases. Optimal
      activity was at pH 6 and 55 degrees C. XylB was stable from pH 4.5 to 10 and up
      to 60 degrees C. It was non-glycosylated. The apparent K(m) and V(max) values of
      XylB on birch wood xylan were 0.53 mg ml(-1) and 0.2 mmol min-1 mg-1,
      respectively. The activity of XylB was not inhibited by Cd2+, Zn2+, Co2+, EDTA,
      iodoacetamide, beta-mercaptoethanol and acetic anhydride but strongly inhibited
      by 10 mm of N-bromosuccinimide, Hg2+, Pb2+ and p-hydroxymercuric benzoate. XylB
      is an endoxylanase since it hydrolysed xylan resulting the formation of xylo
      oligomers but not of xylose residues.

PMID- 15483389
TI  - Quantitative detection of methylated SOCS-1 , a tumor suppressor gene, by a
      modified protocol of quantitative real time methylation-specific PCR using SYBR
      green and its use in early gastric cancer detection.
AB  - Although methylation-specific PCR (MSP) is a sensitive technique in the detection
      of DNA hypermethylation, it is not quantitative. Here we described a modified PCR
      protocol to quantify methylated SOCS-1 gene by real time MSP using SYBR green,
      which involves an additional PCR step after the 72 degrees C extension step. This
      modified protocol is also useful in the quantitative detection of methylated SOCS
      1 gene in serum samples of gastric cancer patients.

PMID- 15483390
TI  - Inter-simple sequence repeat markers and flow cytometry for the characterization
      of closely related Citrus limon germplasms.
AB  - The genetic relationship among commercial cultivars of Citrus limon (lemon) was
      analysed by inter-simple sequence repeats (ISSR) and flow cytometry techniques.
      Two cultivars with a close germplasm were distinguished by screening 10 SSR
      primers and by measuring DNA content of prestained nuclei.

PMID- 15483391
TI  - Improved process for exopolysaccharide production by Klebsiella pneumoniae sp.
      pneumoniae by a fed-batch strategy.
AB  - Exopolysaccharide (EPS) was produced by Klebsiella pneumoniae K63 grown in fed
      batch cultures using different procedures of the supply of carbon or nitrogen (N)
      source, or both. Cultures grown with excess of glucose and limitation or
      exhaustion of N produced 54.8 and 47.4 g(EPS) l(-1), respectively. These cultures
      also led to an accumulation of 'overflow' metabolites representing more than 16%
      of carbon conversion. The consistency indexes ( K ) obtained to the end of the
      cultures, characteristic of the rheological property of the biopolymer, were 16.4
      Pa s(n) for N deficiency and 5.2 Pa s(n) for N limitation conditions. The
      simultaneous limitation of glucose and N decreased the excretion of co
      metabolites (6.4% of carbon conversion) and the EPS production (18.1 g(EPS) l(
      1)), while improving the quality of the polysaccharide, characterized by the
      highest K of 126.2 Pa s(n) and the highest pseudoplasticity degree (flow
      behaviour index, n=0.2).

PMID- 15483392
TI  - Buffering capacity of whole corn mash alters concentrations of organic acids
      required to inhibit growth of Saccharomyces cerevisiae and ethanol production.
AB  - Growth of Saccharomyces cerevisiae and fermentative ethanol production in the
      presence of acetic and lactic acids was measured in whole corn mash. In this
      industrial medium, as compared to glucose minimal medium, the yeast had increased
      tolerance to organic acid stress. It was concluded that the increased buffering
      capacity of whole corn mash, resulting in decreased concentration of
      undissociated acid, was responsible for this phenomenon.

PMID- 15483393
TI  - Using an Hebbian learning rule for multi-class SVM classifiers.
AB  - Regarding biological visual classification, recent series of experiments have
      enlighten the fact that data classification can be realized in the human visual
      cortex with latencies of about 100-150 ms, which, considering the visual pathways
      latencies, is only compatible with a very specific processing architecture,
      described by models from Thorpe et al. Surprisingly enough, this experimental
      evidence is in coherence with algorithms derived from the statistical learning
      theory. More precisely, there is a double link: on one hand, the so-called Vapnik
      theory offers tools to evaluate and analyze the biological model performances and
      on the other hand, this model is an interesting front-end for algorithms derived
      from the Vapnik theory. The present contribution develops this idea, introducing
      a model derived from the statistical learning theory and using the biological
      model of Thorpe et al. We experiment its performances using a restrained sign
      language recognition experiment. This paper intends to be read by biologist as
      well as statistician, as a consequence basic material in both fields have been
      reviewed.

PMID- 15483394
TI  - A nonlinear model of the behavior of simple cells in visual cortex.
AB  - Despite their structured receptive fields (RFs) and the strong linear components
      in their responses, most simple cells in mammalian visual cortex exhibit
      nonlinear behaviors. Besides the contrast-response function, nonlinearities are
      evident in various types of failure at superposition tasks, in the disagreement
      between direction indices computed from drifting and counterphase flickering
      gratings, in various forms of response suppression (including end- and side
      stopping, spatial-frequency-specific inhibition and cross-orientation
      inhibition), in the advance of phase with increasing contrast, and in phase
      insensitive and frequency-doubled responses to counterphase flickering gratings.
      These behaviors suggest that nonlinearities are involved in the operation of
      simple cells, but current models fail to explain them. A quantitative model is
      presented here that purports to describe basic and common principles of operation
      for all visual cortical cells. Simple cells are described as receiving afferents
      from multiple subunits that differ in their individual RFs and temporal impulse
      responses (TIRs). Subunits are independent and perform a spatial integration
      across their RFs followed by halfwave rectification and temporal convolution with
      their TIRs. This parallel operation yields a set of temporal functions
      representing each subunit's contribution to the membrane potential of the host
      cell, whose final form is given by the weighted sum of all subunits'
      contributions. By varying the number of subunits and their particular
      characteristics, different instances of the model are obtained each of which
      displays a different set of behaviors. Extensive simulation results are presented
      that illustrate how all of the reported nonlinear behaviors of simple cells arise
      from these multi-subunit organizations.

PMID- 15483395
TI  - Extracting information from the power spectrum of synaptic noise.
AB  - In cortical neurons, synaptic "noise" is caused by the nearly random release of
      thousands of synapses. Few methods are presently available to analyze synaptic
      noise and deduce properties of the underlying synaptic inputs. We focus here on
      the power spectral density (PSD) of several models of synaptic noise. We examine
      different classes of analytically solvable kinetic models for synaptic currents,
      such as the "delta kinetic models," which use Dirac delta functions to represent
      the activation of the ion channel. We first show that, for this class of kinetic
      models, one can obtain an analytic expression for the PSD of the total synaptic
      conductance and derive equivalent stochastic models with only a few variables.
      This yields a method for constraining models of synaptic currents by analyzing
      voltage-clamp recordings of synaptic noise. Second, we show that a similar
      approach can be followed for the PSD of the the membrane potential (Vm) through
      an effective-leak approximation. Third, we show that this approach is also valid
      for inputs distributed in dendrites. In this case, the frequency scaling of the
      Vm PSD is preserved, suggesting that this approach may be applied to
      intracellular recordings of real neurons. In conclusion, using simple
      mathematical tools, we show that Vm recordings can be used to constrain kinetic
      models of synaptic currents, as well as to estimate equivalent stochastic models.
      This approach, therefore, provides a direct link between intracellular recordings
      in vivo and the design of models consistent with the dynamics and spectral
      structure of synaptic noise.

PMID- 15483396
TI  - Model of the early development of thalamo-cortical connections and area
      patterning via signaling molecules.
AB  - The mammalian cortex is divided into architectonic and functionally distinct
      areas. There is growing experimental evidence that their emergence and
      development is controlled by both epigenetic and genetic factors. The latter were
      recently implicated as dominating the early cortical area specification. In this
      paper, we present a theoretical model that explicitly considers the genetic
      factors and that is able to explain several sets of experiments on cortical area
      regulation involving transcription factors Emx2 and Pax6, and fibroblast growth
      factor FGF8. The model consists of the dynamics of thalamo-cortical connections
      modulated by signaling molecules that are regulated genetically, and by axonal
      competition for neocortical space. The model can make predictions and provides a
      basic mathematical framework for the early development of the thalamo-cortical
      connections and area patterning that can be further refined as more experimental
      facts become known.

PMID- 15483398
TI  - Distinct dynamics of Aurora B and Survivin during mitosis.
AB  - We have studied the dynamics of Aurora B and Survivin during mitosis in living
      cells, using C-terminal GFP chimeras of the two proteins. These chimeras showed
      identical localization and behave as bona fide wild type proteins. The mobility
      of Aurora B-GFP and Survivin-GFP was analyzed by FRAP. The data show that
      Survivin-GFP, in contrast to Aurora B-GFP, is highly mobile at prometaphase and
      metaphase. At telophase and cell cleavage, both chimeras are found to be fully
      immobile. The ablation of Aurora B by siRNA results in a dramatic decrease of the
      Survivin-GFP mobility. These results demonstrate that Survivin, but not Aurora B,
      is weakly associated with the centromeric chromatin at prometaphase and
      metaphase. The weak association of Survivin with centromeric chromatin is
      dependent on the presence of Aurora B and is not affected by treatment with
      either nocodazole or taxol. The rapid and conditional interchange between
      passenger proteins that we show by live imaging indicates that the high affinity
      interactions demonstrated with in vitro analysis of passenger protein binding
      are, in fact, static "snapshots" of highly dynamic and regulated in vivo
      interactions in mitotic cells.

PMID- 15483399
TI  - Structure-forming CAG/CTG repeat sequences are sensitive to breakage in the
      absence of Mrc1 checkpoint function and S-phase checkpoint signaling:
      implications for trinucleotide repeat expansion diseases.
AB  - Expansion of trinucleotide repeat sequences is the cause of multiple inherited
      human genetic diseases including Huntington's disease and myotonic dystrophy. CTG
      and CAG repeats have been shown to form stable secondary structures that can
      impair Okazaki fragment processing and may impede replication fork progression.
      We recently showed that mutation of DNA damage checkpoint proteins results in
      increased chromosome breaks at expanded CAG/CTG repeats and in increased repeat
      instability (expansions and contractions).(1) Here we report that long CAG
      approximately 155 tracts are especially sensitive to the absence of Mrc1
      (Claspin) checkpoint function, implicating the S-phase checkpoint in maintenance
      of trinucleotide repeats and other secondary-structure forming sequences. Based
      on all of our results, we propose a model for the detection of different types of
      structures by different checkpoint signaling pathways.

PMID- 15483397
TI  - Model for transition from waves to synchrony in the olfactory lobe of Limax.
AB  - A biophysical model for the interactions between bursting (B) cells and
      nonbursting (NB) cells in the procerebral lobe of Limax is developed and tested.
      Phase-sensitivity of the NB cells is exhibited due to the strong inhibition from
      the rhythmically bursting B cells. Electrical and chemical junctions coupled with
      a parameter gradient lead to sustained periodic waves in the lobe. Excitatory
      interactions between the NB cells, which rarely fire, lead to stimulus evoked
      synchrony in the lobe oscillations. A novel calcium current is suggested to
      explain the effects of nitric oxide (NO) on the lobe. Gap junctions are shown
      both experimentally and through simulations to be required for the oscillating
      field potentials.

PMID- 15483400
TI  - Genome wide expression profiling of angiogenic signaling and the Heisenberg
      uncertainty principle.
AB  - Genome wide DNA expression profiling coupled with antibody array experiments
      using endostatin to probe the angiogenic signaling network in human endothelial
      cells were performed. The results reveal constraints on the measuring process
      that are of a similar kind as those implied by the uncertainty principle of
      quantum mechanics as described by Werner Heisenberg. We describe this analogy and
      argue for its heuristic utility in the conceptualization of angiogenesis as an
      important step in tumor formation.

PMID- 15483401
TI  - Novel predicted peptidases with a potential role in the ubiquitin signaling
      pathway.
AB  - A multi-pronged strategy including extensive sequence searches, structural
      modeling, and analysis of contextual information extracted from domain
      architectures, genetic screens, and large-scale protein-protein interaction
      analyses was employed to predict previously undetected components of the
      eukaryotic ubiquitin (Ub) signaling system. Two novel groups of proteins that are
      likely to function as de-ubiquitinating and de-SUMOylating peptidases (DUBs) were
      identified. The first group of putative DUBs, designated PPPDE superfamily (after
      Permuted Papain fold Peptidases of DsRNA viruses and Eukaryotes), consists of
      predicted thiol peptidases with a circularly permuted papain-like fold. The
      inference of the likely DUB function of the PPPDE superfamily proteins is based
      on the fusions of the catalytic domain to Ub-binding PUG (PUB)/UBA domains and a
      novel alpha-helical Ub-associated domain (the PUL domain, after PLAP, Ufd3p and
      Lub1p). The presence of the PPPDE superfamily proteins in most eukaryotic
      lineages, including basal ones, such as Giardia, suggests a role in
      deubiquitination of highly conserved proteins involved in key cellular functions,
      such as cell cycle control. In addition to eukaryotic proteins, the PPPDE
      superfamily includes predicted proteases from several groups of double-stranded
      RNA viruses and one single-stranded DNA virus. The apparent recruitment of DUBs
      for viral polyprotein processing seems to represent a common theme in evolution
      of viruses. The second group of putative DUBs identified in this study is the WLM
      (Wss1p-like metalloproteases) family of the Zincin-like superfamily of Zn
      dependent peptidases, which are linked to the Ub-system by virtue of fusions with
      the UB-binding PUG (PUB), Ub-like, and Little Finger domains. More specifically,
      genetic evidence implicates the WLM family in de-SUMOylation. If validated
      experimentally, the WLM family proteins will represent the first case of a Zincin
      like metalloprotease involvement in Ub-signaling.

PMID- 15483402
TI  - Checking out the centrosome.
AB  - Centrosomes consist of a pair of barrel-shaped microtubule assemblies called
      centrioles, surrounded by a pericentriolar matrix. The only well-characterized
      functions of centrosomes is to recognize both interphase microtubule arrays
      responsible for cell polarity and the mitotic spindle, which mediates the
      strictly bipolar separations of chromosomes. In addition to these established
      functions it has been speculated that centrosomes might be involved in several
      different cell cycle regulatory events like entry into mitosis, cytokinesis,
      G(1)/S transition and monitoring of DNA damage. These assumptions are mainly
      based on a rapidly growing list of centrosome-associated regulatory proteins such
      as p53, Brca1, Chk1, Chk2, TopBP1, Aurora-A, Plk1, cyclin B1, and Cdk1. However,
      only very few direct links between their localization to the centrosome and
      specific cellular functions have been unraveled until recently. This review will
      focus on recent advances in the understanding of the role of centrosomes as
      integrators of positive and negative pathways for mitotic entry.

PMID- 15483403
TI  - Chk1 versus Cdc25: chking one's levels of cellular proliferation.
AB  - This review summarizes recent studies which have provided new insight into the
      mechanisms by which the DNA damage response kinase, Chk1 inhibits the dual
      specificity phosphatase, Cdc25, and thereby regulates cell cycle progression.
      Recently, Chk1 has been shown to not only regulate Cdc25A degradation but also
      its ability to interact with various Cdk complexes through phosphorylation of the
      carboxy-terminus of the phosphatase. Surprisingly, these effects appear to be
      specific for Chk1, but not Chk2, which may explain the recently reported in vivo
      haploinsufficiency phenotype observed in the mammary gland using a Chk1
      conditional mouse model.

PMID- 15483405
TI  - Recombinant urokinase is safe and effective in restoring patency to occluded
      central venous access devices: a multiple-center, international trial.
AB  - BACKGROUND: The treatment of choice for central venous access device (CVAD)
      occlusion is intracatheter thrombolysis, which has been reported to reestablish
      patency in up to 80% of cases. However, these salient results have only been
      achieved in highly selected CVAD subgroups such as nontunneled devices in adult
      patients, devices with recent occlusion, and in partially occluded devices
      through which fluid can still be infused (withdrawal occlusions). Less is known
      about the success of intracatheter thrombolysis in the broader range of CVAD
      malfunction encountered in clinical practice, especially in those devices that
      are totally occluded. OBJECTIVE: This multiple-center, open-label study was
      performed to test the hypothesis that a new recombinant urokinase (r-UK,
      urokinase alfa) is safe and effective in reestablishing patency in a large
      unselected cohort of occluded CVADs. METHODS: Pediatric and adult patients with
      any type of CVAD occlusion of any duration were treated with 5000 IU/mL
      intracatheter r-UK. Lumen patency was assessed after 5, 15, and 30 mins; a second
      dose of r-UK was instilled if the catheter remained occluded after 30 mins.
      RESULTS: A total of 903 r-UK instillations were performed in 878 patients (age
      range, 16 days to 96 yrs). Overall, instillation of r-UK successfully restored
      total catheter patency (all treated lumens) to 75% of CVADs (681 of 902). Patency
      was restored to at least one occluded lumen in 79% of devices (712 of 902).
      Patency was restored equally in catheters with total occlusion (76%) as in
      catheters with only withdrawal occlusion (75%). The median +/- sd time to patency
      was 15 +/- 20.8 mins (range, 5-203 mins). CONCLUSION: The use of a new r-UK, 5000
      IU/mL, is safe and effective for the restoration of patency to occluded CVADs.

PMID- 15483406
TI  - Acute pancreatitis in mice impairs bacterial clearance from the lungs, whereas
      concurrent pneumonia prolongs the course of pancreatitis.
AB  - OBJECTIVE: Nosocomial pneumonia is a feared complication in the critically ill
      patient. Serious acute pancreatitis is frequently complicated by infections. The
      objectives of this study were to determine the influence of acute pancreatitis on
      host defense against Pseudomonas pneumonia and to determine the influence of
      Pseudomonas pneumonia on the severity of concurrent pancreatitis. DESIGN: A
      controlled, in vivo laboratory study. SETTING: Research laboratory of a health
      sciences university. SUBJECTS: Female C57Bl/6 mice. INTERVENTIONS: Pancreatitis
      was induced by 12 hourly intraperitoneal injections of cerulein (pancreatitis) or
      saline (sham) immediately followed by intranasal administration of Pseudomonas
      aeruginosa (to induce pneumonia) or saline (controls). Mice were killed 24 hrs
      later. Hence, four groups were studied: sham/control, pancreatitis/control,
      sham/pneumonia, and pancreatitis/pneumonia mice. MEASUREMENTS AND MAIN RESULTS:
      When compared with sham/pneumonia mice, pancreatitis/pneumonia mice demonstrated
      exaggerated lung inflammation, higher bacterial counts in lungs and pancreas, and
      enhanced dissemination of the infection. Concurrently, pneumonia prolonged the
      course of pancreatitis, as reflected by histopathology and higher plasma amylase
      and relative pancreas weights (all p < .05 for the difference between
      pancreatitis/pneumonia and pancreatitis/control mice), which was associated with
      the localization of Pseudomonas in the pancreas. CONCLUSIONS: Acute pancreatitis
      impairs host defense against Pseudomonas pneumonia, whereas pneumonia prolongs
      the course of pancreatitis.

PMID- 15483407
TI  - Outcomes of patients with do-not-intubate orders treated with noninvasive
      ventilation.
AB  - OBJECTIVE: To determine whether diagnosis and bedside observations predict
      outcomes of patients who have declined intubation but accept noninvasive positive
      pressure ventilation (NPPV) to treat their respiratory failure. DESIGN:
      Prospective multiple-center cohort trial. SETTING: Two teaching hospitals and two
      community-based hospitals in southeastern New England from January through
      October 1999. PATIENTS: All patients receiving NPPV for acute respiratory failure
      were screened and enrolled if they had a written do-not-intubate (DNI) order.
      INTERVENTIONS: Patients were begun on NPPV with mean inspiratory and expiratory
      pressures of 13.4 +/- 0.3 and 5.0 +/- 1 cm H2O, respectively. Respiratory
      therapists recorded demographic information, blood gases, and ventilator type and
      settings, and they made bedside assessments of cough strength, presence of airway
      secretions, awake state, and agitation. Patients were followed until discharge
      for duration of NPPV, survival status, and disposition. MEASUREMENTS AND MAIN
      RESULTS: Of 1,211 screened patients, 114 had a DNI status and were enrolled into
      the study. Of these, 49 (43%) survived to discharge. Age, gender, location in a
      community vs. teaching hospital, and initial pH and PaO2 did not affect survival,
      but a higher baseline PaCO2 was associated with a favorable odds ratios for
      survival to discharge. Diagnosis was an important determinant of survival, with
      congestive heart failure patients having significantly better survival rates than
      those with chronic obstructive pulmonary disease, cancer, pneumonia, or other
      diagnoses. A stronger cough and being awake were also associated with increased
      probability of survival. CONCLUSION: Patients with respiratory failure and a DNI
      status have a high overall mortality rate when treated with NPPV, but those with
      diagnoses such as congestive heart failure or chronic obstructive pulmonary
      disease, who have a strong cough, or who are awake have better prognoses. These
      data should be useful when counseling DNI patients and their families on use of
      NPPV.

PMID- 15483409
TI  - Eliminating catheter-related bloodstream infections in the intensive care unit.
AB  - OBJECTIVE: To determine whether a multifaceted systems intervention would
      eliminate catheter-related bloodstream infections (CR-BSIs). DESIGN: Prospective
      cohort study in a surgical intensive care unit (ICU) with a concurrent control
      ICU. SETTING: The Johns Hopkins Hospital. PATIENTS: All patients with a central
      venous catheter in the ICU. INTERVENTION: To eliminate CR-BSIs, a quality
      improvement team implemented five interventions: educating the staff; creating a
      catheter insertion cart; asking providers daily whether catheters could be
      removed; implementing a checklist to ensure adherence to evidence-based
      guidelines for preventing CR-BSIs; and empowering nurses to stop the catheter
      insertion procedure if a violation of the guidelines was observed. MEASUREMENT:
      The primary outcome variable was the rate of CR-BSIs per 1,000 catheter days from
      January 1, 1998, through December 31, 2002. Secondary outcome variables included
      adherence to evidence-based infection control guidelines during catheter
      insertion. MAIN RESULTS: Before the intervention, we found that physicians
      followed infection control guidelines during 62% of the procedures. During the
      intervention time period, the CR-BSI rate in the study ICU decreased from
      11.3/1,000 catheter days in the first quarter of 1998 to 0/1,000 catheter days in
      the fourth quarter of 2002. The CR-BSI rate in the control ICU was 5.7/1,000
      catheter days in the first quarter of 1998 and 1.6/1,000 catheter days in the
      fourth quarter of 2002 (p = .56). We estimate that these interventions may have
      prevented 43 CR-BSIs, eight deaths, and 1,945,922 dollars in additional costs per
      year in the study ICU. CONCLUSIONS: Multifaceted interventions that helped to
      ensure adherence with evidence-based infection control guidelines nearly
      eliminated CR-BSIs in our surgical ICU.

PMID- 15483408
TI  - Prevention of stress ulceration: current trends in critical care.
AB  - OBJECTIVE: To identify the level of current intensivist's knowledge regarding
      risk assessment and intensive care unit (ICU) clinical practice pertaining to
      stress-related mucosal bleeding, including pharmacologic approaches for stress
      ulcer prevention. DESIGN: A nationwide survey of critical care physicians. STUDY
      POPULATION: Two thousand random physician members of the Society of Critical Care
      Medicine. MEASUREMENTS AND MAIN RESULTS: The response rate was 519 (26%) of 2000,
      with data analysis from 501 (25.1%) usable surveys. Respondents were affiliated
      with internal medicine (44.3%), surgery (42.3%), and anesthesiology (12.6%). Gut
      ischemia was indicated as the perceived major cause of stress ulceration (59.7%).
      The estimated incidence of clinically important bleeding was 2% or less by 62% of
      respondents; however, 28.6% of physicians surveyed initiate stress ulcer
      prophylaxis in all ICU patients, regardless of bleeding risk. Respiratory failure
      was most frequently indicated as a reason for stress ulcer prophylaxis (68.6%),
      followed by shock/hypotension (49.4%), sepsis (39.4%), and head injury/major
      neurologic insult (35.2%). The first-line agents selected for stress ulcer
      prophylaxis include histamine-2 receptor antagonists (63.9%), followed by proton
      pump inhibitors (23.1%), and sucralfate (12.2%). Concern for nosocomial pneumonia
      was regarded as more prevalent with antisecretory therapies in those who chose
      sucralfate (61%) as initial therapy compared with overall respondents (26.9%) (p
      < .001). CONCLUSIONS: The majority of intensivists surveyed recognize stress
      related mucosal bleeding as a relatively infrequent event; however,
      implementation of a stress ulcer prophylaxis risk stratification scheme for ICU
      patients is necessary. Histamine-2 receptor antagonists are consistently
      perceived as appropriate initial agents, although proton pump inhibitors have
      become first-line therapy in an increasing percentage of critical care patients,
      despite limited data regarding their use in this population.

PMID- 15483410
TI  - The effect of anti-L-selectin (aselizumab) in multiple traumatized patients-
      results of a phase II clinical trial.
AB  - OBJECTIVE: The objectives of this study were to evaluate safety (primary) and
      clinical efficacy (secondary) of the humanized monoclonal anti-L-selectin
      antibody aselizumab in severely injured patients. DESIGN: Prospective phase II,
      parallel group, double-blind, randomized, placebo-controlled clinical trial.
      SETTING: Fourteen medical intensive care units or trauma units in level I trauma
      centers in Belgium, Germany, and Poland. PATIENTS: Eighty-four patients with a
      sustained trauma due to a blunt or penetrating injury and a total Injury Severity
      Scale score of > or =25. INTERVENTIONS: Patients received either aselizumab at
      dosages of 0.5, 1, or 2 mg/kg or placebo within 6 hrs of the traumatic event and
      were followed for 6 wks. MEASUREMENTS AND MAIN RESULTS: The number of expeditable
      adverse events increased dose dependently over the aselizumab groups compared
      with placebo. There were no statistically significant differences between all
      groups regarding leukopenia and risk of infection. No immunologic response
      following infusion of aselizumab was noted. The number of patients with multiple
      organ failure, defined as a median value of the total Goris Multiple Organ
      Failure score of > or =5 on > or =2 consecutive days within 14 days, was not
      significantly different for the 0.5 mg/kg, 1 mg/kg, 2 mg/kg, and placebo groups.
      There were no statistically significant differences in time of mechanical
      ventilation, length of stay in an intensive care unit, and total duration of
      hospitalization between treatment groups. CONCLUSIONS: Aselizumab was associated
      with a higher rate of infections and leucopenia; however, this difference was not
      significantly different compared with placebo. For all efficacy variables,
      aselizumab presented no significant trends but only a few scattered statistically
      significant differences between groups.

PMID- 15483411
TI  - Morbidity in hospitalized patients receiving human albumin: a meta-analysis of
      randomized, controlled trials.
AB  - OBJECTIVE: To determine the effect of albumin administration on morbidity in
      acutely ill hospitalized patients. DATA SOURCE: Computer searches of MEDLINE,
      EMBASE, and the Cochrane Library; hand searches of journals and Index Medicus;
      inquiries with investigators and fluid product suppliers; and examination of
      reference lists. No language or time period restrictions were adopted. STUDY
      SELECTION: Randomized, controlled trials comparing the administration of albumin
      with that of crystalloid, no albumin, or lower-dose albumin. DATA EXTRACTION: Two
      investigators independently extracted data. The primary endpoint for the meta
      analysis was morbidity, defined as the incidence of complications, including
      death. Trial quality was evaluated by blinding, allocation concealment, presence
      of morbidity as a study endpoint, and individual patient crossover. DATA
      SYNTHESIS: Seventy-one trials were included in the categories of surgery or
      trauma, burns, hypoalbuminemia, high-risk neonates, ascites, and other
      indications. The 3,782 randomized patients in the included trials experienced a
      total of 3,287 complications, including 515 deaths and 2,772 cardiovascular,
      gastrointestinal, hepatic, infectious, renal, respiratory, and other
      complications. Albumin significantly reduced overall morbidity, with a risk ratio
      of 0.92 (confidence interval [CI], 0.86-0.98). Control group albumin dose
      significantly affected the incidence of complications (p = .002). In 32 trials
      with no albumin administered to the control group, the risk ratio was 0.77 (CI,
      0.67-0.88) compared with 0.89 (CI, 0.80-1.00) in 20 trials with control patients
      receiving low-dose albumin and 1.07 (CI, 0.96-1.20) in 19 trials with moderate
      dose control group albumin. CONCLUSIONS: Albumin reduces morbidity in acutely ill
      hospitalized patients. Concomitant administration of albumin in the control group
      can obscure the effects of albumin on clinical outcome in randomized trials.

PMID- 15483412
TI  - Positive end-expiratory pressure affects regional redistribution of ventilation
      differently in prone and supine sheep.
AB  - OBJECTIVE: To examine interactions between positive end-expiratory pressure
      (PEEP) and posture on regional distribution of ventilation and to compare
      measurements of regional ventilation with two aerosols: a wet fluorescent
      microsphere aerosol (FMS, median mass aerodynamic diameter 1.1 microm) and a dry
      Tc-labeled carbon particle aerosol (Technegas, TG, median mass aerodynamic
      diameter approximately 0.1 microm). DESIGN: Experimental study. SETTING: Academic
      laboratory. SUBJECTS: : Anesthetized and mechanically ventilated sheep (n = 16).
      INTERVENTIONS: Four conditions were studied: prone or supine posture with or
      without 10 cm H2O PEEP. MEASUREMENTS AND MAIN RESULTS: Comparisons of FMS and TG
      were made in five animals. The median correlation coefficient of the two
      ventilation tracers was .95 (range, .91-.96). The mean ventilation per unit
      weight of dry lung for horizontal planes was almost identical whether measured
      with TG or FMS. The distribution of ventilation was assessed by analyzing
      deposition of aerosol in about 1,000 lung regions per animal. Distribution of
      ventilation down the vertical axis was linear in prone (the slope indicated a
      dorsal-to-ventral three-fold difference in ventilation) but unimodal in supine
      animals with the mode in the center of the lung. Redistribution of ventilation
      with 10 PEEP differed between posture, shifting the mode in supine toward
      dependent lung regions while eliminating the dorsal-to-ventral gradient in prone.
      The regional heterogeneity in ventilation was greater in supine sheep at both
      levels of PEEP, and this was due mostly to greater isogravitational heterogeneity
      in supine than in prone position. CONCLUSIONS: The wet fluorescent microsphere
      aerosol was as reliable as Technegas for high-resolution measurements of regional
      ventilation. The markedly different effects of 10 PEEP in supine and prone sheep
      may have important implications for gas exchange both in noninjured and injured
      lungs.

PMID- 15483413
TI  - Suppressive oligodeoxynucleotides inhibit CpG-induced inflammation of the mouse
      lung.
AB  - OBJECTIVE: To examine the effect of suppressive oligodeoxynucleotides (ODNs) on
      the pulmonary inflammation induced by immunostimulatory CpG DNA. DESIGN:
      Prospective, randomized, controlled study. SETTING: Research laboratories.
      SUBJECTS: RAW 264.7 murine macrophage-like cell line and BALB/c mice.
      INTERVENTIONS: RAW 264.7 cells were incubated with bacterial DNA or CpG ODN,
      alone or combined with suppressive ODN. The in vivo effect of suppressive ODN was
      determined using an acute lung injury model. CpG ODN alone or combined with
      suppressive ODN was instilled into the mouse lung. MEASUREMENTS AND MAIN RESULTS:
      Production of tumor necrosis factor (TNF)-alpha and macrophage inflammatory
      protein (MIP)-2 by RAW 264.7 cells were measured by enzyme-linked immunosorbent
      assay (ELISA), whereas their messenger RNA levels were determined by reverse
      transcriptase-polymerase chain reaction. Synthetic ODN containing CpG motifs (CpG
      ODN) mimicked the ability of bacterial DNA to stimulate the production of TNF
      alpha and MIP-2. Suppressive ODN significantly inhibited the activation of RAW
      264.7 cells by both bacterial DNA and CpG ODN. In the lung injury model,
      production of proinflammatory cytokines (TNF-alpha and IL-6) and chemokines (MIP
      2 and KC) in bronchoalveolar lavage (BAL) fluids was measured by ELISA.
      Neutrophil accumulation in the alveolar spaces was also evaluated. Instillation
      of CpG ODN into the lungs of normal mice triggered the synthesis of TNF-alpha, IL
      6, MIP-2, and KC. Suppressive ODN significantly blocked the production of these
      proinflammatory cytokines and chemokines and also reduced neutrophil mobilization
      into the alveolar spaces by CpG DNA. CONCLUSIONS: Proinflammatory cytokines and
      chemokines are up-regulated by CpG motifs in bacterial DNA. Suppressive ODN
      significantly inhibits the inflammatory response induced by CpG DNA in murine
      macrophages and the lung. This study supports the use of suppressive ODN to
      reduce the deleterious inflammatory responses induced by bacterial DNA.

PMID- 15483414
TI  - In silico experiments of existing and hypothetical cytokine-directed clinical
      trials using agent-based modeling.
AB  - OBJECTIVES: To introduce a form of mathematical modeling, agent-based modeling
      (ABM), and demonstrate its potential uses in the evaluation of the dynamics of
      the innate immune response (IIR) and the development of possible treatments for
      systemic inflammatory response syndrome (SIRS)/multiple organ failure (MOF).
      RATIONALE: The IIR can be categorized as a complex system that responds to
      interventions in a nonintuitive fashion, leading to difficulty in translating
      basic science knowledge into effective treatments for SIRS/MOF. It is proposed
      that ABM is particularly well suited to examining the complex interactions of the
      IIR and its disordered states of SIRS/MOF. STUDY DESIGN: Computer simulation and
      mathematical modeling. DATA SOURCE: Review articles on components and mechanisms
      involved in the IIR. Published results from phase III anticytokine/mediator
      trials. Published results from smaller clinical trials and animal studies. MAIN
      RESULTS: An abstract ABM of the IIR was created. The model reproduces the general
      behavior of the IIR with respect to outcome and cause of system "death." Patterns
      of levels of individual cytokines matched patterns of measured cytokines reported
      in the existing literature. Clinical trials of anticytokine therapy were
      simulated and produced outcomes qualitatively similar to those reported in the
      literature. A series of hypothetical treatment regimes (variation of dose and
      length of treatment [anti-tumor necrosis factor and anti-interleukin-1], anti-CD
      18, and multiple-drug regimes [combination of anti-tumor necrosis factor, anti
      interleukin-1, and anti-CD-18]) were formulated and implemented in the ABM. None
      of the simulated therapies showed a statistically significant improvement in
      system mortality. CONCLUSIONS: Presented herein is an abstracted ABM of the IIR.
      This model is intended primarily as an introduction to and demonstration of this
      technique. However, even this relatively simple model demonstrates
      counterintuitive system responses and the difficulty of effectively manipulating
      a complex system like the IIR. ABM may provide a synthetic, analytical platform
      to integrate basic science data on the IIR, thus eventually aiding in formulating
      and testing future mediator-directed therapies for SIRS/MOF before clinical
      trials, and it may provide insights into directions of future research.

PMID- 15483415
TI  - In silico design of clinical trials: a method coming of age.
AB  - OBJECTIVE: To determine the feasibility and potential usefulness of mathematical
      models in evaluating immunomodulatory strategies in clinical trials of severe
      sepsis. DESIGN: Mathematical modeling of immunomodulation in simulated patients.
      SETTING: Computer laboratory. MEASUREMENTS AND MAIN RESULTS: We introduce and
      evaluate the concept of conducting a randomized clinical trial in silico based on
      simulated patients generated from a mechanistic mathematical model of bacterial
      infection, the acute inflammatory response, global tissue dysfunction, and a
      therapeutic intervention. Trial populations are constructed to reflect
      heterogeneity in bacterial load and virulence as well as propensity to mount and
      modulate an inflammatory response. We constructed a cohort of 1,000 trial
      patients submitted to therapy with one of three different doses of a neutralizing
      antibody directed against tumor necrosis factor (anti-TNF) for 6, 24, or 48 hrs.
      We present cytokine profiles over time and expected outcome for each cohort. We
      identify subgroups with high propensity for being helped or harmed by the
      proposed intervention and identify early serum markers for each of those
      subgroups. The mathematical simulation confirms the inability of simple markers
      to predict outcome of sepsis. The simulation clearly separates cases with
      favorable and unfavorable outcome on the basis of global tissue dysfunction.
      Control survival was 62.9% at 1 wk. Depending on dose and duration of treatment,
      survival ranged from 57.1% to 80.8%. Higher doses of anti-TNF, although
      effective, also result in considerable harm to patients. A statistical analysis
      based on a simulated cohort identified markers of favorable or adverse response
      to anti-TNF treatment. CONCLUSIONS: A mathematical simulation of anti-TNF therapy
      identified clear windows of opportunity for this intervention as well as
      populations that can be harmed by anti-TNF therapy. The construction of an in
      silico clinical trial could provide profound insight into the design of clinical
      trials of immunomodulatory therapies, ranging from optimal patient selection to
      individualized dosage and duration of proposed therapeutic interventions.

PMID- 15483417
TI  - Protective effect of N-acetylcysteine and deferoxamine on carbon tetrachloride
      induced acute hepatic failure in rats.
AB  - OBJECTIVE: Carbon tetrachloride (CCl4) is a lipid-soluble potent hepatotoxic;
      thus, it widely is used as an animal model of severe hepatic failure. Treatment
      with antioxidants may modulate the toxic effects of CCl4 on liver, generally with
      drug administration before CCl4, which can restrict its use in the clinical
      setting. We here describe the effects of N-acetylcysteine, deferoxamine, or both
      in the treatment of CCl4-induced hepatic failure. DESIGN: Prospective,
      randomized, controlled experiment. SETTING: Animal basic science laboratory.
      SUBJECTS: Male Wistar rats, weighing 200-250 g. INTERVENTIONS: Rats exposed to
      CCl4 were treated with N-acetylcysteine and/or deferoxamine or vehicle.
      MEASUREMENTS AND MAIN RESULTS: N-acetylcysteine plus deferoxamine treatment
      significantly attenuated hepatic and central nervous system oxidative damage
      after acute hepatic failure induced by CCl4. In addition, the serum levels of
      alanine aminotransferase, total bilirubin, and prothrombin time in the N
      acetylcysteine plus deferoxamine group were significantly lower than those in the
      N-acetylcysteine or deferoxamine and saline groups. After N-acetylcysteine plus
      deferoxamine treatment, hepatocellular necrosis and inflammatory infiltration
      induced by carbon tetrachloride were greatly decreased. Survival in untreated
      rats was 5%. Survival increased to 25% and 35%, respectively, with N
      acetylcysteine and deferoxamine treatment. In rats treated with N-acetylcysteine
      plus deferoxamine, survival was 80%. CONCLUSIONS: Our data provide the first
      experimental demonstration that N-acetylcysteine plus deferoxamine reduces
      mortality rate, decreases oxidative stress, and limits inflammatory infiltration
      and hepatocyte necrosis induced by CCl4 in the rat.

PMID- 15483416
TI  - Evaluation of continuous aspiration of subglottic secretion in an in vivo study.
AB  - OBJECTIVE: Continuous aspiration of subglottic secretions (CASS) is believed to
      lower the incidence of ventilator-associated pneumonia. Animal studies to
      establish safety and efficacy of CASS have not been conducted. DESIGN:
      Prospective randomized animal study. SETTING: Animal-research facility at the
      U.S. National Institutes of Health. SUBJECTS: Twenty-two sheep. INTERVENTIONS:
      Sheep were randomized into three groups. In group C (control), eight sheep were
      kept prone, intubated with a standard endotracheal tube (ETT), and mechanically
      ventilated for 72 hrs with head and ETT elevated at an angle of 30 degrees. In
      group CASS-HU (CASS, head up), seven sheep were managed as group C and intubated
      with a Hi-Lo Evac, Mallinckrodt ETT (CASS suction kept at < or =20 mm Hg). In
      group CASS-HD (CASS, head down), seven sheep were kept prone with CASS, and the
      ETT and trachea were horizontal to promote spontaneous drainage of mucus from the
      ETT. MEASUREMENTS AND RESULTS: The lower respiratory tract in the CASS-HU group
      was heavily colonized in all seven sheep (median 4.6 x 10(9), range, 1.5 x 10(8)
      to 7.9 x 10(9) colony-forming units/g), with a reduction of lung bacterial
      colonization compared with the C group (p = .05). In group CASS-HD, the lower
      respiratory tract was not colonized in six of seven sheep. One sheep showed low
      levels of bacterial growth (median, 0; range, 0-2.2 x 10(5)). At autopsy, in all
      14 sheep with CASS, we found tracheal mucosal injury of different degrees of
      severity at the level of the suction port of the ETT. CONCLUSIONS: In group CASS
      HU, regardless of finding a marginal decrease of the bacterial colonization of
      the lower airways, there was pervasive trachea-bronchial-lung bacterial
      colonization. Second, there was minimal, or absent, bacterial colonization when
      the orientation of the CASS ETT was at, or just below, horizontal. Third, there
      was widespread injury to tracheal mucosa/submucosa from the use of CASS. Note
      that results of studies conducted in an animal model are always difficult to
      extrapolate to the clinical practice due to anatomical and functional
      differences.

PMID- 15483418
TI  - Partial liquid ventilation with FC-77 suppresses the release of lipid mediators
      in rat acute lung injury model.
AB  - OBJECTIVE: To investigate whether the release of lipid mediators is suppressed in
      rats with experimentally induced acute lung injury managed with partial liquid
      ventilation (PLV) using FC-77. DESIGN: Prospective, randomized controlled study.
      SETTING: Research laboratory in a university. SUBJECTS: Male Sprague-Dawley rats.
      INTERVENTIONS: After tracheostomy was performed under general anesthesia, lung
      injury was induced by intratracheal instillation of HCl. The PLV group was then
      subjected to conventional gas ventilation for 30 mins, followed by PLV using FC
      77. The control group was subjected to conventional gas ventilation throughout
      the study period. MEASUREMENTS AND MAIN RESULTS: In the PLV group the following
      results were obtained: a) impaired oxygenation was markedly improved; b) the
      increase in the serum levels of lipid mediators such as leukotriene B4,
      thromboxane A2, and 6-keto-prostaglandin F1alpha was suppressed; and c) the
      increase in the concentrations of leukotriene B4, thromboxane A2, and 6-keto
      prostaglandin F1alpha in the total lung homogenate at 180 mins after lung injury
      was also suppressed. CONCLUSION: This study indicates that PLV using FC-77
      suppresses the release of lipid mediators in our rat model of acute lung injury.
      However, further investigation is needed to clarify the precise mechanism of this
      effect.

PMID- 15483419
TI  - Continuous positive airway pressure delivered with a "helmet": effects on carbon
      dioxide rebreathing.
AB  - OBJECTIVE: The "helmet" has been used as a novel interface to deliver noninvasive
      ventilation without applying direct pressure on the face. However, due to its
      large volume, the helmet may predispose to CO2 rebreathing. We hypothesized that
      breathing with the helmet is similar to breathing in a semiclosed environment,
      and therefore the PCO2 inside the helmet is primarily a function of the subject's
      CO2 production and the flow of fresh gas through the helmet. DESIGN: Human
      volunteer study. SETTING: Laboratory in a university teaching hospital. SUBJECTS:
      Eight healthy volunteers. INTERVENTIONS: We delivered continuous positive airway
      pressure (CPAP) with the helmet under a variety of ventilatory conditions in a
      lung model and in volunteers. MEASUREMENTS AND MAIN RESULTS: Gas flow and CO2
      concentration at the airway were measured continuously. End-tidal PCO2, CO2
      production, and ventilatory variables were subsequently computed. We found that
      a) when CPAP was delivered with a ventilator, the inspired CO2 of the volunteers
      was high (12.4 +/- 3.2 torr [1.7 +/- 0.4 kPa]); b) when CPAP was delivered with a
      continuous high flow system, inspired CO2 of the volunteers was low (2.5 +/- 1.2
      torr [0.3 +/- 0.2 kPa]); and c) the inspired CO2 calculated mathematically for a
      semiclosed system model of CO2 rebreathing was highly correlated with the values
      measured in a lung model (r = .97, slope = 0.92, intercept = -1.17, p < .001) and
      in the volunteers (r = .94, slope = 0.96, intercept = 0.90, p < .001).
      CONCLUSIONS: a) The helmet predisposes to CO2 rebreathing and should not be used
      to deliver CPAP with a ventilator; b) continuous high flow minimizes CO2
      rebreathing during CPAP with the helmet; and c) minute ventilation and Pco2
      should be monitored during CPAP with the helmet.

PMID- 15483421
TI  - A prototype of a liquid ventilator using a novel hollow-fiber oxygenator in a
      rabbit model.
AB  - OBJECTIVE: A functional total liquid ventilator should be simple in design to
      minimize operating errors and have a low priming volume to minimize the amount of
      perfluorocarbon needed. Closed system circuits using a membrane oxygenator have
      partially met these requirements but have high resistance to perfluorocarbon flow
      and high priming volume. To further this goal, a single piston prototype
      ventilator with a low priming volume and a new high-efficiency hollow-fiber
      oxygenator in a circuit with a check valve flow control system was developed.
      DESIGN: Prospective, controlled animal laboratory study. SETTING: Research
      facility at a university medical center. SUBJECTS: Seven anesthetized, paralyzed,
      normal New Zealand rabbits INTERVENTIONS: The prototype oxygenator, consisting of
      cross-wound silicone hollow fibers with a surface area of 1.5 m2 with a priming
      volume of 190 mL, was tested in a bench-top model followed by an in vivo rabbit
      model. Total liquid ventilation was performed for 3 hrs with 20 mL.kg(-1) initial
      fill volume, 17.5-20 mL.kg(-1) tidal volume, respiratory rate of 5 breaths/min,
      inspiratory/expiratory ratio 1:2, and countercurrent sweep gas of 100% oxygen.
      MEASUREMENTS AND MAIN RESULTS: Bench top experiments demonstrated 66-81%
      elimination of CO2 and 0.64-0.76 mL.min(-1) loss of perfluorocarbon across the
      fibers. No significant changes in PaCO2 and PaO2 were observed. Dynamic airway
      pressures were in a safe range in which ventilator lung injury or airway closure
      was unlikely (3.6 +/- 0.5 and -7.8 +/- 0.3 cm H2O, respectively, for mean peak
      inspiratory pressure and mean end expiratory pressure). No leakage of
      perfluorocarbon was noted in the new silicone fiber gas exchange device.
      Estimated in vivo perfluorocarbon loss from the device was 1.2 mL.min(-1).
      CONCLUSIONS: These data demonstrate the ability of this novel single-piston,
      nonporous hollow silicone fiber oxygenator to adequately support gas exchange,
      allowing successful performance of total liquid ventilation.

PMID- 15483420
TI  - Theaflavin, a black tea extract, is a novel anti-inflammatory compound.
AB  - OBJECTIVE: Tea has been around for centuries, and its medicinal properties have
      been purported in the literature but never fully confirmed. Interleukin-8 is a
      principle neutrophil chemoattractant and activator in humans. We determined the
      effects of theaflavin, a black tea-derived polyphenol, on tumor necrosis factor
      alpha-mediated expression of the interleukin-8 gene in A549 cells. DESIGN:
      Prospective laboratory study. SETTING: University laboratory. SUBJECTS: A549
      cells. INTERVENTIONS: A549 cells were exposed to varying concentrations of
      theaflavin and analyzed for tumor necrosis factor-alpha-mediated interleukin-8
      gene expression. MEASUREMENTS AND MAIN RESULTS: Theaflavin inhibited tumor
      necrosis factor-alpha-mediated interleukin-8 gene expression, as measured by
      luciferase assay and Northern blot analysis, at concentrations of 10 and 30
      microg/mL. This effect appears to primarily involve inhibition of interleukin-8
      transcription because theaflavin inhibited tumor necrosis factor-alpha-mediated
      activation of the interleukin-8 promoter in cells transiently transfected with an
      interleukin-8 promoter-luciferase reporter plasmid. In addition, theaflavin
      inhibited tumor necrosis factor-alpha-mediated activation of IkappaB kinase and
      subsequent activation of the IkappaB-alpha/nuclear factor-kappaB pathway.
      Theaflavin also significantly reduced tumor necrosis factor-alpha-mediated DNA
      binding of activator protein-1. CONCLUSIONS: We conclude that theaflavin is a
      potent inhibitor of interleukin-8 gene expression in vitro. The proximal
      mechanism of this effect involves, in part, inhibition of IkappaB kinase
      activation and activator protein-1 pathway.

PMID- 15483423
TI  - Guidelines and levels of care for pediatric intensive care units.
AB  - The practice of pediatric critical care medicine has matured dramatically during
      the past decade. These guidelines are presented to update the existing guidelines
      published in 1993. Pediatric critical care services are provided in level I and
      level II units. Within these guidelines, the scope of pediatric critical care
      services is discussed, including organizational and administrative structure,
      hospital facilities and services, personnel, drugs and equipment, quality
      monitoring, and training and continuing education.

PMID- 15483422
TI  - Mild hypothermia during prolonged cardiopulmonary cerebral resuscitation
      increases conscious survival in dogs.
AB  - OBJECTIVE: Therapeutic hypothermia during cardiac arrest and after restoration of
      spontaneous circulation enables intact survival after prolonged cardiopulmonary
      cerebral resuscitation (CPCR). The effect of cooling during CPCR is not known. We
      hypothesized that mild to moderate hypothermia during CPCR would increase the
      rate of neurologically intact survival after prolonged cardiac arrest in dogs.
      DESIGN: Randomized, controlled study using a clinically relevant cardiac arrest
      outcome model in dogs. SETTING: University research laboratory. SUBJECTS: Twenty
      seven custom-bred hunting dogs (19-29 kg; three were excluded from outcome
      evaluation). INTERVENTIONS: Dogs were subjected to cardiac arrest no-flow of 3
      mins, followed by 7 mins of basic life support and 10 mins of simulated
      unsuccessful advanced life support attempts. Another 20 mins of advanced life
      support continued with four treatments: In control group 1 (n = 7), CPCR was with
      normothermia; in group 2 (n = 6, 1 of 7 excluded), with moderate hypothermia via
      venovenous extracorporeal shunt cooling to tympanic temperature 27 degrees C; in
      group 3 (n = 6, 2 of 8 excluded), the same as group 2 but with mild hypothermia,
      that is, tympanic temperature 34 degrees C; and in group 4 (n = 5), with
      normothermic venovenous shunt. After 40 mins of ventricular fibrillation,
      reperfusion was with cardiopulmonary bypass for 4 hrs, including defibrillation
      to achieve spontaneous circulation. All dogs were maintained at mild hypothermia
      (tympanic temperature 34 degrees C) to 12 hrs. Intensive care was to 96 hrs.
      MEASUREMENTS AND MAIN RESULTS: Overall performance categories and neurologic
      deficit scores were assessed from 24 to 96 hrs. Regional and total brain
      histologic damage scores and extracerebral organ damage were assessed at 96 hrs.
      In normothermic groups 1 and 4, all 12 dogs achieved spontaneous circulation but
      remained comatose and (except one) died within 58 hrs with multiple organ
      failure. In hypothermia groups 2 and 3, all 12 dogs survived to 96 hrs without
      gross extracerebral organ damage (p < .0001). In group 2, all but one dog
      achieved overall performance category 1 (normal); four of six dogs had no
      neurologic deficit and normal brain histology. In group 3, all dogs achieved good
      functional outcome with normal or near-normal brain histology. Myocardial damage
      scores were worse in the normothermic groups compared with both hypothermic
      groups (p < .01). CONCLUSION: Mild or moderate hypothermia during prolonged CPCR
      in dogs preserves viability of extracerebral organs and improves outcome.

PMID- 15483424
TI  - Prognostic value of S100B protein in carbon monoxide-poisoned rats.
AB  - OBJECTIVE: To assess the possible role of S100B, a structural protein of
      astroglial cells, as a biochemical marker in acute carbon monoxide-poisoned rats
      and to compare its prognostic value with consciousness level, which is one of the
      major parameters for treatment decision in acute carbon monoxide poisoning.
      DESIGN: Nonrandomized, controlled interventional trial. SETTING: University
      laboratory. SUBJECTS: Male Wistar rats weighing 263 +/- 18 g. INTERVENTIONS: The
      rats were exposed to a mixture of 3000 ppm carbon monoxide in air for 60 mins
      (group 1) and a mixture of 5000 ppm carbon monoxide in air for 30 mins (group 2).
      Blood samples were taken from the jugular vein just before and immediately after
      the carbon monoxide poisoning. The level of consciousness was evaluated at the
      end of the exposure, and the survival rate was monitored for 7 days. The S100B
      concentrations were measured with a commercial immunoluminometric assay.
      MEASUREMENTS AND MAIN RESULTS: In the first group, the unconscious rats after
      carbon monoxide exposure had significantly higher S100B levels compared with the
      rats without loss of consciousness. In the second group, the unconscious rats
      that later died had significantly higher S100B levels compared with the
      unconscious rats that survived. The S100B levels of all conscious and unconscious
      surviving rats were not significantly different. The serum level of S100B below
      0.44 microg/L predicted survival of carbon monoxide-poisoned rats, with a
      sensitivity of 100% and a specificity of 86%. CONCLUSIONS: Acute carbon monoxide
      poisoning is associated with elevated S100B levels. S100B is a better predictor
      of final outcome than the consciousness level, so it could be used as a
      prognostic parameter for acute carbon monoxide poisoning in rats.

PMID- 15483425
TI  - Lipopolysaccharide challenge causes exaggerated fever and increased hepatic
      lipopolysaccharide uptake in vinblastine-induced leukopenic guinea pigs.
AB  - OBJECTIVE: To better understand the pathophysiology of the fever often manifested
      by immunocompromised patients undergoing chemotherapy that become neutropenic and
      suffer a bacterial infection. DESIGN: Prospective animal study. SETTING: A
      physiology laboratory in a medical school setting. MEASUREMENTS AND MAIN RESULTS:
      We induced leukopenia in guinea pigs with vinblastine (0.7 mg/kg, intravenously,
      4 days before) and measured the animals' febrile response to 2 microg of
      lipopolysaccharide/kg and the uptake of 75 microg of fluorescein isothiocyanate
      labeled lipopolysaccharide/kg by Kupffer cells. The leukopenic animals exhibited
      significantly higher fevers and greater hepatic fluorescein isothiocyanate
      lipopolysaccharide uptake than their controls. CONCLUSION: Lipopolysaccharide
      challenged, vinblastine-induced leukopenic guinea pigs exhibit hyperpyrexia and
      significantly elevated uptake of lipopolysaccharide by Kupffer cells, the major
      source of pyrogenic mediators. This could explain "febrile neutropenia."

PMID- 15483426
TI  - Sepsis: an arginine deficiency state?
AB  - OBJECTIVE: Sepsis is a major health problem considering its significant morbidity
      and mortality rate. The amino acid L-arginine has recently received substantial
      attention in relation to human sepsis. However, knowledge of arginine metabolism
      during sepsis is limited. Therefore, we reviewed the current knowledge about
      arginine metabolism in sepsis. DATA SOURCE: This review summarizes the literature
      on arginine metabolism both in general and in relation to sepsis. Moreover,
      arginine-related therapies are reviewed and discussed, which includes therapies
      of both nitric oxide (NO) and arginine administration and therapies directed
      toward inhibition of NO. DATA: In sepsis, protein breakdown is increased, which
      is a key process to maintain arginine delivery, because both endogenous de novo
      production from citrulline and food intake are reduced. Arginine catabolism, on
      the other hand, is markedly increased by enhanced use of arginine in the arginase
      and NO pathways. As a result, lowered plasma arginine levels are usually found.
      Clinical symptoms of sepsis that are related to changes in arginine metabolism
      are mainly related to hemodynamic alterations and diminished microcirculation. NO
      administration and arginine supplementation as a monotherapy demonstrated
      beneficial effects, whereas nonselective NO synthase inhibition seemed not to be
      beneficial, and selective NO synthase 2 inhibition was not beneficial overall.
      CONCLUSIONS: Because sepsis has all the characteristics of an arginine-deficiency
      state, we hypothesise that arginine supplementation is a logical option in the
      treatment of sepsis. This is supported by substantial experimental and clinical
      data on NO donors and NO inhibitors. However, further evidence is required to
      prove our hypothesis.

PMID- 15483427
TI  - Thrombolytics for occluded catheters.

PMID- 15483428
TI  - Do not get sick when you are sick: the impact of comorbid conditions.

PMID- 15483429
TI  - Which patient with a do-not-intubate order is a candidate for noninvasive
      ventilation?

PMID- 15483430
TI  - Eliminating catheter-related bloodstream infections: fairy tale or new reality?

PMID- 15483431
TI  - Targeting leukocyte trafficking in the treatment of severe trauma.

PMID- 15483432
TI  - Albumin versus crystalloid solutions for the critically ill and injured.

PMID- 15483433
TI  - The deceptive complexity of "simple" proning.

PMID- 15483434
TI  - Through a glass darkly: the brave new world of in silico modeling.

PMID- 15483435
TI  - In vivo, in vitro, in silico...

PMID- 15483436
TI  - Do not suction above the cuff.

PMID- 15483437
TI  - Noninvasive interfaces: should we go to helmets?

PMID- 15483438
TI  - Hypothermia during cardiac arrest: moving from defense to offense.

PMID- 15483439
TI  - A more appropriate critical appraisal of the available evidence?

PMID- 15483441
TI  - DES, not always the best!

PMID- 15483442
TI  - No argument for not accepting a single, well-performed trial for the highest
      level of recommendation.

PMID- 15483448
TI  - Cardiovascular disease in chronic kidney disease from a cardiologist's
      perspective.
AB  - PURPOSE OF REVIEW: Cardiovascular disease accounts for the majority of morbidity
      and mortality in patients with chronic kidney disease (CKD). This review
      therefore concentrates on CKD from the viewpoint of the cardiologist. RECENT
      FINDINGS: Studies have identified several explanations for this observation,
      including high rates of risk factors for cardiovascular disease, lesser use of
      cardioprotective strategies, adverse outcomes with cardiovascular drugs and
      procedures, and accelerated atherosclerosis and myocardial disease in CKD.
      Because recent studies have rigorously controlled for confounding factors, there
      is an emerging recognition that CKD is an independent cardiovascular risk state.
      Conversely, CKD appears to be the result of systemic atherosclerosis. The
      relative under-utilization of cardioprotective therapies has been an increasingly
      reported finding in the literature. It appears that conventional cardiovascular
      risk factor reduction in both the chronic and acute care settings has a greater
      relative benefit in those patients with CKD than in those with normal renal
      function. SUMMARY: CKD is an independent cardiovascular risk state. Hence, there
      is a strong rationale for research in CKD patients into the pathogenesis of CVD.
      In addition, there are multiple opportunities for improving cardiovascular
      outcomes in patients with CKD, including both chronic and acute cardiovascular
      risk reduction.

PMID- 15483449
TI  - Statin therapy in kidney disease populations: potential benefits beyond lipid
      lowering and the need for clinical trials.
AB  - PURPOSE OF REVIEW: This review outlines the limited information currently
      available on the effects of statins among patients with chronic kidney disease,
      and summarizes the ongoing randomized trials designed to address this question.
      RECENT FINDINGS: The effects of fluvastatin on major coronary events among renal
      transplant patients, and the effects of pravastatin and simvastatin in small
      subgroups of coronary patients with minor degrees of renal impairment, appear
      broadly compatible with those observed in trials conducted in non-renal
      populations. In addition, recent evidence from trials among patients with
      vascular disease or diabetes suggests that statin therapy may delay progressive
      loss of renal function. However, there remains substantial uncertainty regarding
      the effects of statin therapy among patients with established chronic kidney
      disease (pre-dialysis or dialysis patients). In particular, there does not appear
      to be a strongly positive relationship between blood cholesterol and
      cardiovascular events in such patients. This may be because uraemic
      cardiomyopathy and arteriosclerosis, which cause the majority of these events in
      chronic kidney disease patients, do not depend strongly on blood cholesterol.
      SUMMARY: Statins appear effective for the prevention of vascular events in people
      with established vascular disease and mild renal impairment, and may delay renal
      disease progression in such individuals. However, the effects of statins in
      patients with established chronic kidney disease are unknown, and we await the
      results of ongoing large-scale randomized trials of statin therapy among such
      patients.

PMID- 15483450
TI  - Chronic kidney disease progression in native and transplant kidneys.
AB  - PURPOSE OF REVIEW: The present review addresses the recent literature
      demonstrating important differences in the rate of progression of kidney function
      decline between transplant recipients and patients with native kidney disease. It
      also highlights the need for prospective studies to determine the importance of
      nonimmune factors that are established risk factors for progression of native
      kidney disease in the transplant setting. RECENT FINDINGS: Transplant recipients
      establish modest levels of kidney function but have rates of kidney function
      decline that are slower than those in patients with native kidney disease.
      Continued improvements in long-term graft survival have not been achieved despite
      significant advances in immunosuppression. There is increasing observational
      evidence that nonimmune factors that play a causal role in progression of native
      kidney disease may also be important determinants of allograft decline. There are
      fundamental differences between transplant recipients and patients with native
      kidney disease that preclude extrapolation of evidence from native kidney disease
      to the transplant setting. SUMMARY: Transplant recipients are a unique group of
      chronic kidney disease patients. Prospective studies to determine the importance
      of nonimmune factors such as hypertension, proteinuria, dyslipidemia, diabetes,
      and anemia in the transplant setting are needed.

PMID- 15483451
TI  - Atherosclerotic renal artery stenosis: current status and future directions.
AB  - PURPOSE OF REVIEW: Atherosclerotic renal artery stenosis is a common, progressive
      problem that increases in prevalence with age. It can have important clinical
      consequences such as hypertension, pulmonary edema, and renal failure. In
      addition, it is associated with increased cardiovascular mortality. The purpose
      of this review is to describe the current status of knowledge and future
      directions for this evolving field. RECENT FINDINGS: In patients who are
      suspected of having the disease, duplex Doppler ultrasound and magnetic resonance
      angiography remain the most promising noninvasive screening tests. Percutaneous
      revascularization continues to advance, and technical success is possible in the
      vast majority of patients. Revascularization for hypertension is of modest
      clinical benefit. Limited information is available on the effect of
      revascularization on preservation of renal function or cardiovascular events and
      mortality. SUMMARY: Further studies are still needed focusing on the
      identification of which patients will derive benefit from percutaneous
      revascularization and whether intervention provides an advantage over medical
      therapy, particularly with respect to preservation of renal function and
      reduction in cardiovascular morbidity and mortality.

PMID- 15483452
TI  - Vascular access for hemodialysis: 2004 and beyond.
AB  - PURPOSE OF REVIEW: Developments in vascular access are accruing rapidly. The last
      systematic Kidney Disease Outcomes Quality Initiative guidelines review took
      place in 2000. The purpose of this review is to update several major areas in
      which clear progress has been made. A major 'Fistula First Initiative' in the USA
      is an attempt to increase markedly the fraction of patients receiving an
      autologous arteriovenous fistula as opposed to a graft. Preoperative mapping to
      evaluate veins and artery may permit construction of arteriovenous fistula in up
      to 70% of all patients, thereby reducing access thrombosis, infection, and
      perhaps increasing survival of patients. RECENT FINDINGS: Although a number of
      different synthetic materials have been tried, none seems to have any definite
      advantage over plain expanded polytetrafluoroethylene for constructing synthetic
      bridge grafts. Two developments may influence practice: use of composite self
      sealing grafts that can be used within hours may eliminate the need for temporary
      catheters; and use of nitinol surgical clips may reduce endothelial trauma and
      improve patency. Large-bore catheters can deliver blood flows of over 400 ml/min
      initially, but they are prone to progressive occlusion. Optimal means of using a
      fibrinolytic to preserve flow must be evaluated. Surveillance techniques are
      undergoing rapid re-evaluation. Finally, a variety of antibiotic lock techniques
      are being evaluated for their ability to prevent catheter-related infections.
      SUMMARY: Greater efforts must be made to establish pre-end-stage renal disease
      programs to educate and prepare patients for hemodialysis and improve
      arteriovenous fistula placement rates, and to encourage clinicians to re-examine
      their current clinical practices and dedicate themselves to improving vascular
      access outcomes.

PMID- 15483453
TI  - Is more frequent hemodialysis beneficial and what is the evidence?
AB  - PURPOSE OF REVIEW: The HEMO study results have shown that increasing dialysis
      dose in conventional thrice weekly hemodialysis does not improve patient
      outcomes. Interest has therefore turned to more frequent (daily) hemodialysis
      treatments. This review covers the rationale for such an approach together with a
      current review of the published study data. RECENT FINDINGS: Recent studies have
      suggested improvements in a number of intermediate patient outcomes such as
      cardiovascular (blood pressure control, left ventricular hypertrophy), anemia,
      phosphate control, nutritional status and quality of life. Some of these outcomes
      are associated with increased survival in the dialysis population. SUMMARY: The
      inference from these studies is that more frequent hemodialysis will indeed
      reduce mortality and morbidity. To date, however, the studies have all been small
      and underpowered to detect such primary outcomes. No randomized controlled trials
      are yet reported. The US National Institutes of Health have sponsored larger
      scale North American based studies and an International Registry of Daily
      Dialysis patients has been created to attain further information of the possible
      benefits of such therapy. In spite of the paucity of hard evidence the studies to
      date have been enough to convince some jurisdictions to recognize and fund daily
      hemodialysis treatments.

PMID- 15483454
TI  - Imaging and assessment of vascular calcification in chronic kidney disease
      patients.

PMID- 15483455
TI  - The use of extracellular matrix probes and extracellular matrix-related probes
      for assessing diagnosis and prognosis in renal diseases.
AB  - PURPOSE OF REVIEW: Scarring in the kidney results from excessive local synthesis
      and exogenous accumulation of extracellular matrix components. Once chronic
      damage is present in the biopsy, therapeutic intervention for the renal patient
      encounters severe limitations. It is therefore essential to determine clinical
      outcome preferably at a time point before the development of overt scarring.
      Clinical parameters and morphologic alterations in the biopsy are currently used
      as tools for the diagnosis of the renal disease entity and for assessment of the
      patient's prognosis. Expression levels of extracellular matrix and matrix-related
      components may serve as additive and even superior prognostic indicators to
      conventional parameters. We will elaborate on studies supporting this concept.
      RECENT FINDINGS: Several investigators have shown in experimental models for
      renal disease that extracellular matrix probes and related probes reflect disease
      progression and predict outcome. In this review, we will provide an update on the
      most recent studies of human renal biopsies showing that expression of
      extracellular matrix components, regulators of matrix degradation, and cytokines
      affecting matrix deposition may be employed for discrimination of diagnostic
      groups and predicting prognosis. SUMMARY: Molecular techniques are expected to be
      used more and more for diagnostic and prognostic purposes in nephrological
      practice to supplement the histopathological analysis of the renal biopsy.
      Assessment of expression of matrix molecules, matrix-regulating cytokines, and
      metalloproteinases in renal kidney biopsies is helpful to distinguish patients
      who are at risk of developing progressive renal failure from patients who are
      likely to recover from renal tissue injury by natural remodeling mechanisms.

PMID- 15483456
TI  - N-Acetylcysteine in nephrology; contrast nephropathy and beyond.
AB  - PURPOSE OF REVIEW: Since the first publication appeared in 2000 showing that
      prophylactic oral administration of the antioxidant acetylcysteine, along with
      adequate hydration, can prevent the reduction in renal function induced by non
      ionic, low-osmolality contrast agents, acetylcysteine has rapidly become widely
      used in clinical practice. Meanwhile, other applications of acetylcysteine in
      nephrology have been reported. This review analyses recent literature on the
      effects of acetylcysteine on radiocontrast-induced nephropathy, on plasma
      homocysteine concentrations, and on cardiovascular events in patients with end
      stage renal failure. RECENT FINDINGS: At least 19 randomized trials evaluating
      acetylcysteine for the prevention of radiocontrast-induced nephropathy, at least
      five meta-analyses, and several reviews on that topic have been published within
      the past 4 years. The studies on radiocontrast-induced nephropathy showed
      remarkably mixed results, probably as a result of study heterogeneity. One study
      recently indicated that the administration of acetylcysteine during a
      haemodialysis session significantly lowered plasma homocysteine concentrations.
      Another study indicated that long-term antioxidative treatment with
      acetylcysteine significantly reduced cardiovascular events in patients with end
      stage renal failure. SUMMARY: Although there are controversies on dosing and
      timing, the use of acetylcysteine together with hydration should be considered to
      protect patients from radiographic contrast media-induced nephropathy. Long-term
      antioxidative treatment with acetylcysteine in patients with end-stage renal
      failure may also be useful to prevent adverse cardiovascular events.

PMID- 15483457
TI  - Monitoring and maintenance of arteriovenous fistulae and graft function in
      haemodialysis patients.
AB  - PURPOSE OF REVIEW: Several options exist for detecting and preventing stenosis in
      polytetrafluoroethylene grafts and arteriovenous fistulae for haemodialysis.
      Although observational studies show a significant benefit of such strategies,
      data from randomized trials are limited. This review describes recently published
      information that has helped to advance this field during the past year. RECENT
      FINDINGS: A new method for the measurement of access blood flow is discussed.
      This technique does not require special apparatus, which may facilitate its use
      in settings where resources are limited. The utility and potential shortcomings
      of access blood flow monitoring in grafts and fistulae are discussed, focusing on
      three key controlled studies published during the past year. Although much
      additional research is needed, regular access blood flow monitoring may improve
      outcomes in fistulae. Although there is less evidence that access blood flow
      monitoring is beneficial in grafts, regular dynamic venous pressure monitoring
      seems reasonable, because it can detect stenosis at a low capital cost. Neither
      radiotherapy nor combination therapy with aspirin and clopidogrel are useful for
      the prevention of stenosis in grafts. SUMMARY: Large randomized trials of
      screening appear feasible for both types of permanent vascular access. Given the
      adverse patient outcomes associated with access failure, as well as the high
      costs attributable to the implementation of ineffective screening strategies,
      such trials should be a high priority for nephrology researchers.

PMID- 15483458
TI  - Renal biopsy: update.
AB  - PURPOSE OF REVIEW: The renal biopsy is an invaluable tool in the diagnosis,
      prognosis, and management of patients with kidney disease. As the success of the
      procedure is defined not only by the ability to obtain adequate tissue but also
      by the safety profile, significant advances which define risk factors and
      determine the optimal timing of observation after the percutaneous native renal
      biopsy merit discussion. Alternative methods of obtaining tissue, such as
      transvenous renal biopsies, have also been described, especially in patients with
      contraindications to the percutaneous method. RECENT FINDINGS: The percutaneous
      renal biopsy has been established as a safe and effective method of obtaining
      renal parenchyma. Complications, although rare, may occur and the majority of
      these are related to bleeding. The optimal timing of observation after the biopsy
      should be determined by when most complications occur, and, as over 33% of
      complications occur after 8 h, an observation period of at least 24 h is
      recommended. In patients with contraindications to the percutaneous approach,
      such as failure of adequate radiologic visualization or a bleeding diathesis,
      alternative methods of obtaining tissue have been attempted. These include open,
      laparascopic, transurethral, or transvenous renal biopsy. SUMMARY: Without
      contraindications, the percutaneous renal biopsy remains the standard method of
      acquiring renal tissue. At least 24 h of observation is recommended after the
      percutaneous native kidney biopsy for the development of potential complications.
      When a contraindication to the procedure exists, other methods of renal biopsy by
      experienced physicians may be attempted.

PMID- 15483459
TI  - Renal magnetic resonance imaging.
AB  - PURPOSE OF REVIEW: Current magnetic resonance imaging systems allow the
      visualization of normal and diseased kidney, with exquisite resolution of renal
      structures. Dynamic contrast magnetic resonance imaging has the potential, unique
      among all noninvasive modalities, to differentiate diseases that affect different
      portions of the vascular-nephron system. This article reviews the most important
      recently published studies in selected topics chosen because of their clinical
      relevance or potential for technical developments. RECENT FINDINGS: Magnetic
      resonance imaging is used increasingly to evaluate renal masses, the prenatal
      genitourinary system, urinary obstruction and infection, renal vasculature, and
      the kidneys of transplant donors and recipients. Dynamic contrast magnetic
      resonance renography based on gadolinium chelated to diethylenetriamine
      pentaacetic acid, a safe (non-nephrotoxic) paramagnetic agent, emerges as the
      functional renal imaging modality of choice. Both perfusion and filtration rates
      can be assessed in individual kidney. SUMMARY: Magnetic resonance imaging has the
      potential to provide a complete anatomic, physiologic, kidney-specific
      evaluation. With future advances in automated image analysis methods we can
      expect functional renal magnetic resonance imaging to play an influential role in
      management of renal disease.

PMID- 15483460
TI  - Sodium-phosphate cotransporters, nephrolithiasis and bone demineralization.
AB  - PURPOSE OF REVIEW: We discuss how recent findings obtained in disorders of
      phosphate metabolism in humans and in animal models have provided insights into
      the pathogenesis of renal stone formation and bone demineralization. RECENT
      FINDINGS: Mice that are null for the sodium-phosphate cotransporter (NPT)2a gene
      (NPT2a(-/-) mice) exhibit hypophosphataemia, increased urinary phosphate
      excretion, hypercalciuria and nephrolithiasis, but no bone demineralization. Mice
      null for the sodium-hydrogen exchanger regulatory factor (NHERF)1 (NHERF1(-/-)
      mice) also exhibit hypophosphataemia and increased renal phosphate excretion with
      decreased renal NPT2a expression, but they present with a severe sex-dependent
      bone demineralization. Heterozygous loss-of-function mutations in the NPT2a gene
      in humans induce hypophosphataemia, increased urinary phosphate excretion,
      hypercalciuria, nephrolithiasis in males (to date) and bone demineralization of
      variable severity in both sexes. Patients and experimental animals with increased
      circulating levels of fibroblast growth factor 23 present with hypophosphataemia,
      increased urinary phosphate excretion, inappropriate calcitriol synthesis and
      rickets/osteomalacia, but no nephrolithiasis except when treated. Low-phosphate
      diet in spontaneously hypercalciuric rats and disruption of the 1-alpha
      hydroxylase gene in NPT2a mice prevent renal stone formation. SUMMARY: Increased
      urinary phosphate excretion is a risk factor for renal calcium stone formation
      when it is associated with hypercalciuria. As yet undefined interplay between
      NPT2a, NHERF1 and possibly other cotransporters or associated proteins in bone
      cells may account for the diversity of bone phenotypes observed in disorders of
      phosphate metabolism with impaired renal phosphate reabsorption. The pathogenesis
      of both renal stone and bone demineralization appear to be affected by species,
      sex and mutation type, among other factors.

PMID- 15483461
TI  - Bibliography. Current world literature. Dialysis and transplantation.

PMID- 15483462
TI  - Protective efficacy of multiepitope human leukocyte antigen-A*0201 restricted
      cytotoxic T-lymphocyte peptide construct against challenge with human T-cell
      lymphotropic virus type 1 Tax recombinant vaccinia virus.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T
      cell leukemia. Multiepitope T-cell vaccines are more likely to generate a broad
      long-lasting immune response than those composed of single epitopes. We recently
      reported a novel multivalent cytotoxic T-lymphocyte peptide construct derived
      from the Tax protein of HTLV-1 separated by arginine spacers that elicited high
      cellular responses against individual epitopes simultaneously in human leukocyte
      antigen (HLA)-A*0201 transgenic mice. We now report the effect of epitope
      orientation on the processing of the multiepitope construct by 20s proteasomes
      and the effect of the processing rates on the immunogenicity of the intended
      epitopes. A positive correlation was found between processing rates and the
      immunogenicity of the intended epitopes. The construct with the highest
      immunogenicity for each epitope was tested for protective efficacy in a
      preclinical model of infection using HTLV-1 Tax recombinant vaccinia virus and
      HLA-A*0201 transgenic mice. Mice vaccinated with the multiepitope construct
      displayed a statistically significant reduction in viral replication that was
      dependent on CD8 T cells. Reduction in viral replication was also confirmed to be
      specific to Tax-vaccinia virus. These results demonstrate the activation of Tax
      specific CD8+ T cells by vaccination and are supportive of a multivalent peptide
      vaccine approach against HTLV-1 infections.

PMID- 15483463
TI  - Patterns of resistance emerging in HIV-1 from antiretroviral-experienced patients
      undergoing intensification therapy with tenofovir disoproxil fumarate.
AB  - Study GS-99-907 was a 48-week, phase 3, double-blind, placebo-controlled
      intensification trial of tenofovir disoproxil fumarate (tenofovir DF).
      Antiretroviral-experienced patients added tenofovir DF 300 mg once daily to their
      existing regimen. The patterns of HIV-1 resistance development and the
      corresponding virologic responses were evaluated in a virology substudy at week
      48. Although 94% of these treatment-experienced patients had nucleoside
      associated resistance mutations (NAMs) at baseline, addition of tenofovir DF
      resulted in a mean reduction in viral load of -0.59 log10 copies/mL after 24
      weeks that was durable through 48 weeks. Relative to the placebo-controlled arm,
      patients in the tenofovir DF arm had a reduced frequency of development of
      resistance mutations to all classes of HIV-1 inhibitors, with reduction in new
      protease inhibitor (PI)-associated mutations achieving statistical significance.
      The K65R mutation, which occurred in 8 patients (3%), was the only emergent
      mutation directly associated with tenofovir DF therapy. New thymidine analogue
      associated mutations (TAMs) emerged in 19% of patients by week 48. Other than
      K65R, the patterns of mutations that developed were not significantly different
      between the tenofovir DF and placebo control arms, suggesting that the background
      therapies caused their development. The K65R mutation emerged only in patients
      with no detectable TAMs at baseline, whereas new TAMs developed similarly between
      patients with or without TAMs at baseline. Development of K65R was associated
      with mostly low-level changes in phenotypic susceptibility to tenofovir DF and
      other nucleoside reverse transcriptase inhibitors and was not associated with
      viral load rebound. No novel patterns of genotypic or phenotypic resistance to
      tenofovir were identified. Therefore, intensification with once-daily tenofovir
      DF therapy resulted in a sustained reduction in HIV-1 viral load and a low risk
      for development of the K65R mutation in this treatment-experienced patient
      population.

PMID- 15483464
TI  - It is safe to stop antiretroviral therapy in patients with preantiretroviral CD4
      cell counts >250 cells/microL.
AB  - OBJECTIVE: To study clinical, immunologic, and virologic outcomes in patients who
      stop antiretroviral therapy (ART) with relatively preserved CD4 cell counts.
      DESIGN AND METHODS: Patients with a documented CD4 cell count >250 cells/microL
      who stopped ART for any reason for at least 5 weeks were studied. Relevant
      clinical and laboratory data were collected using a standardized data collection
      form. MAIN OUTCOME MEASURES: Patients were monitored for outcomes including
      Centers for Disease Control (CDC) category B or C events, time to restarting ART,
      and time to reaching a CD4 cell count of < or = 250 cells/microL. RESULTS: A
      total of 107 patients were included. The median time on ART was 45 months and
      median number of antiretroviral medications was 4. The median pre-ART CD4 cell
      count and HIV viral load were 463 cells/microL and 4.35 log copies/mL,
      respectively. The median CD4 cell at time of ART stop was 739 cell/microL. The
      slope of the CD4 decrease was 65 cells/mo in the first 2 months, which was
      greater than the subsequent decline of 8 cells/mo thereafter (P < 0.01).
      Similarly the median viral load increase was 2.54 log copies/mL in the first 2
      months after stopping and was unchanged after that point. Two patients
      experienced the retroviral rebound syndrome after ART cessation but no CDC
      category B or C events were observed during 10 months of follow-up. The median
      time from stopping ART to reaching the combined endpoint of CD4 <250 or
      restarting ART was 8.9 months. In multivariate analysis, pre-ART CD4 cell count
      >250 was protective of reaching the combined endpoint (odds ratio = 0.156, P =
      0.03). Other predictors of reaching the combined endpoint in multivariate
      analysis were older age and number of prior ART agents. Patients who restarted
      ART had a favorable virologic and immunologic response. CONCLUSIONS: Patients
      with relatively high CD4 cell counts prior to starting ART did well after
      stopping ART. Pre-ART CD4 cell count can be used to predict outcomes after ART
      cessation.

PMID- 15483465
TI  - Comparison of two indinavir/ritonavir regimens in the treatment of HIV-infected
      individuals.
AB  - BACKGROUND: Pharmacokinetic enhancement of protease inhibitors (PIs) with low
      dose ritonavir (RTV) for salvage therapy is increasingly common. The purpose of
      this study was to compare the pharmacokinetics, safety, and tolerability of
      indinavir (IDV)/RTV at 800/200 mg (arm A) and 400/400 mg (arm B) administered
      twice daily in HIV-infected subjects failing their first PI-based regimen.
      METHODS: A phase I/II, randomized, open-label, 24-week study was conducted.
      Formal 12-hour pharmacokinetic evaluations were performed, and study visits
      occurred at baseline; at weeks 1, 2, and 4; and every 4 week thereafter for 24
      weeks. Clinical symptoms and laboratory assessments were collected. Subjects were
      allowed to switch arms because of toxicity. RESULTS: Forty-four subjects were
      enrolled (22 per arm). IDV predose concentration, maximum plasma concentration
      and area under the curve were significantly higher in arm A. Fifty-five percent
      and 45% of subjects in arms A and B responded (<200 copies/mL at week 24; P =
      0.76), respectively. CD4 cell responses were similar. All subjects had IDV
      sensitive virus at baseline and at virologic failure. Tolerability was
      comparable, but all grade 3 or higher triglyceride increases occurred in arm B
      and more subjects in arm B switched because of toxicity (5 vs. 1 triglyceride
      increases). CONCLUSIONS: This is the largest formal pharmacokinetic evaluation of
      2 dosage combinations of IDV/RTV in HIV-infected individuals. Pharmacokinetic
      parameters were consistent with previous results in patients but lower than in
      seronegative controls. Both regimens exhibited similar tolerability and response
      rates. High toxicity with a low response suggests that the optimum IDV/RTV
      combination would include an RTV dose <400 mg and an IDV dose <800 mg in this
      population.

PMID- 15483466
TI  - Factors associated with successful referral for clinical care of drug users with
      chronic hepatitis C who have or are at risk for HIV infection.
AB  - The objective of this study was to determine outcomes of referring drug users
      (DUs) with chronic hepatitis C for clinical evaluation and care. Two hundred
      twenty-eight persons with detectable hepatitis C virus RNA were given expedited
      referrals for evaluation and possible treatment of hepatitis C from a prospective
      study cohort of current and former opiate-addicted DUs. Four outcomes were
      analyzed: accepted referral, arrived for clinical evaluation, had liver biopsy,
      and received treatment. One hundred twenty-seven participants (56%) accepted
      referral, of whom 54 (43%) arrived for evaluation. Of these participants, 12
      (22%) had liver biopsy, and 4 (7%) were treated. Multivariate logistic regression
      revealed that HIV-infected DUs were significantly less likely to accept referral
      (adjusted odds ratio [O(Radj)], 0.51; 95% confidence interval [CI], 0.30-0.88),
      and older participants were more likely to keep an appointment (O(Radj), 1.06/y;
      95% CI, 1.00-1.12). Of HIV-seropositive participants, those with a history of
      injection were more likely to accept referral (O(Radj), 3.60; 95% CI, 1.08
      11.96), and those with higher HIV load (O(Radj), 0.50/log10; 95% CI, 0.26-0.94)
      and Hispanic ethnicity (O(Radj), 0.26; 95% CI, 0.07-0.89) were less likely to
      keep an appointment. Despite expedited referrals for hepatitis C care, only a few
      participants received an evaluation, and even far fewer were treated. Because
      increasingly effective treatment is available, better methods are urgently needed
      to improve evaluation and treatment of HCV-infected DUs, including those
      coinfected with HIV.

PMID- 15483467
TI  - Steady-State pharmacokinetics of saquinavir hard-gel/ritonavir/fosamprenavir in
      HIV-1-infected patients.
AB  - BACKGROUND: In vitro synergy and complementary resistance profiles provide a
      strong rationale for combining fosamprenavir with saquinavir as part of a potent
      double-boosted protease inhibitor regimen. This study evaluated the steady-state
      pharmacokinetics of saquinavir 1000 mg twice daily (bid) and fosamprenavir 700 mg
      bid administered with 2 different doses of ritonavir (100 and 200 mg bid) in HIV
      1-infected subjects. METHODS: On day 1, 12-hour pharmacokinetic profiles for
      saquinavir/ritonavir (1000/100 mg bid) were obtained for 18 subjects. All
      subjects were receiving ongoing treatment with a saquinavir/ritonavir-containing
      regimen. Fosamprenavir 700 mg bid was then added to the regimen, and
      pharmacokinetic sampling was repeated for all 3 agents at day 11. The ritonavir
      daily dose was then increased to 200 mg bid, and a 3rd pharmacokinetic profile
      was obtained at day 22. RESULTS: The coadministration of fosamprenavir 700 mg bid
      with saquinavir/ritonavir 1000/100 mg bid resulted in a statistically
      nonsignificant decrease in saquinavir concentrations (by 14, 9, and 24%, for
      saquinavir area under the concentration-time curve [AUC]0-12, C(max), and
      C(trough), respectively). This was compensated for by an increased ritonavir dose
      of 200 mg bid, which resulted in a statistically nonsignificant increase in
      saquinavir exposure compared with baseline. Amprenavir levels did not appear to
      be significantly influenced by coadministration of saquinavir with fosamprenavir.
      Fosamprenavir significantly reduced ritonavir exposure, but the increased
      ritonavir dose compensated for this interaction. CONCLUSIONS: Our findings showed
      that saquinavir/ritonavir/fosamprenavir was well tolerated over the study period.
      Saquinavir plasma concentrations were slightly lowered by the addition of
      fosamprenavir to the regimen. However, the addition of a further 100 mg ritonavir
      bid restored the small and insignificant decrease.

PMID- 15483468
TI  - Recruitment and baseline epidemiologic profile of participants in the first phase
      3 HIV vaccine efficacy trial.
AB  - OBJECTIVE: To describe recruitment and baseline epidemiologic characteristics of
      volunteers in the first phase 3 placebo-controlled trial of a recombinant gp120
      HIV vaccine (AIDSVAX B/B). METHODS: Volunteers were gay/bisexual men or women at
      risk for sexually transmitted HIV infection. Recruitment strategies,
      demographics, and risk factors were assessed. HIV status was determined by
      standard HIV-1 antibody assays. Seronegative/viremic HIV infection at enrollment
      was determined using the HIV-1 nucleic acid test. RESULTS: From June 1998 through
      October 1999, 5417 of 7185 volunteers screened were enrolled at 61 sites in the
      United States, Canada, and The Netherlands. Successful recruitment methods
      included distribution of study information at gay venues, advertising and media
      coverage, and referrals from volunteers. Most volunteers were altruistically
      motivated, men (98%), young (median, 36 years), white (83%), well educated (61%
      college education or more), and at high risk for HIV during the 6 months before
      enrollment. At baseline, 14 were HIV infected (12 were seronegative but viremic;
      2 were seropositive and viremic). CONCLUSION: Men and women at high risk for
      sexually transmitted HIV infection were successfully recruited for the first
      phase 3 HIV vaccine efficacy trial. Knowledge of recruitment and baseline
      epidemiologic characteristics of participants in this trial will provide valuable
      guidance for designing and conducting future trials.

PMID- 15483469
TI  - Posttrial HIV vaccine adoption: concerns, motivators, and intentions among
      persons at risk for HIV.
AB  - BACKGROUND: Suboptimal uptake of existing vaccines, potential obstacles specific
      to HIV/AIDS stigma and mistrust, and marked health disparities suggest that it is
      vital to investigate consumer concerns, motivations, and adoption intentions
      regarding posttrial HIV vaccines before a vaccine is publicly available. METHOD:
      Nine focus groups were conducted with participants (n = 99; median age, 33 years;
      48% female; 22% African American, 44% Latino, and 28% white) recruited from 7
      high-risk venues in Los Angeles using purposive venue-based sampling. A
      semistructured interview guide elicited concerns, motivators, and adoption
      intentions regarding hypothetical U.S. Food and Drug Administration-approved HIV
      vaccines. Data were analyzed using narrative thematic analysis and Ethnograph
      qualitative software. RESULTS: Concerns included vaccine efficacy, vaccine
      induced infection, vaccine-induced HIV seropositivity, side effects, cost/access,
      trustworthiness, and relationship issues. Motivators included protection against
      HIV infection and the ability to safely engage in unprotected sex. Participants
      expressed reluctance to adopt partial efficacy vaccines and likelihood of
      increased sexual risk behaviors in response to vaccine availability. CONCLUSION:
      Tailored interventions to facilitate uptake of future U.S. Food and Drug
      Administration-approved HIV vaccines and to prevent risk behavior increases may
      be vital to the effectiveness of vaccines in controlling the AIDS pandemic.

PMID- 15483470
TI  - Comparing the cost-effectiveness of HIV prevention interventions.
AB  - OBJECTIVE: Communities need to identify cost-effective interventions for HIV
      prevention to optimize limited resources. METHODS: The authors developed a
      spreadsheet tool using Bernoulli and proportionate change models to estimate the
      relative cost-effectiveness for 26 HIV prevention interventions including
      biomedical interventions, structural interventions, and interventions designed to
      change risk behaviors of individuals. They also conducted sensitivity analyses to
      assess patterns of the cost-effectiveness across different populations using
      various assumptions. RESULTS: The 2 factors most strongly determining the cost
      effectiveness of the different interventions were the HIV prevalence of the
      population at risk and the cost per person reached. In low-prevalence populations
      (eg, heterosexuals) the most cost-effective interventions were structural
      interventions (eg, mass media, condom distribution), whereas in high-prevalence
      populations (eg, men who have sex with men) individually focused interventions to
      change risk behavior were also relatively cost-effective. Among the most cost
      effective interventions overall were showing videos in STD clinics and raising
      alcohol taxes. School-based HIV prevention programs appeared to be the least cost
      effective. Needle exchange and needle deregulation programs were relatively cost
      effective only when injection drug users have a high HIV prevalence. CONCLUSIONS:
      Comparing estimates of the cost-effectiveness of HIV interventions provides
      insight that can help local communities maximize the impact of their HIV
      prevention resources.

PMID- 15483471
TI  - Association of complementary and alternative medicines with HIV clinical disease
      among a cohort of women living with HIV/AIDS.
AB  - To assess the association between the use of complementary and alternative
      medicine (CAM) and HIV clinical disease indicators, CD4+ T-cell counts, viral
      load, number of HIV-related infections, Centers for Disease Control and
      Prevention categories, and Karnofsky scores. Data were collected from 391 HIV
      positive women aged 18 to 50 years in Alabama and Georgia. A survey examining CAM
      use and other sociodemographic variables was used. Multiple logistic regression
      analyses were used to identify predictors of CAM use. Approximately 60% of study
      participants used 1 or more type of CAM. Predictors of CAM use included higher
      educational level (odds ratio [OR] = 2.4; P = 0.0008), absence of health
      insurance (OR = 0.49; P = 0.0055), longer disease duration (OR = 2.21; P =
      0.0006), and higher number of infections (OR = 0.58; P = 0.017). Vitamins were
      the most commonly used CAM ( approximately 36%). Sociodemographic variables
      associated with vitamin use included higher educational level (OR = 2.34; P =
      0.0055), longer disease duration (OR = 1.87; P = 0.026), and higher use among
      white women than among African-American women (OR = 0.41; P = 0.017). The use of
      CAM is prevalent among HIV-positive women, and vitamins are the most commonly
      used CAM among our study population. Several sociodemographic and clinical
      factors predicted CAM use. These findings have implications for improvement of
      care for HIV-positive women.

PMID- 15483472
TI  - Effect of hard-drug use on CD4 cell percentage, HIV RNA level, and progression to
      AIDS-defining class C events among HIV-infected women.
AB  - In vitro and animal studies suggest that cocaine and heroin increase HIV
      replication and suppress immune function, whereas epidemiologic studies are
      inconclusive regarding their effect on HIV infection progression. The authors
      prospectively examined the association between illicit-drug use and 4 outcome
      measures (CD4 cell percentage, HIV RNA level, survival to class C diagnosis of
      HIV infection, and death) in a national cohort of HIV-infected women. Women
      enrolled between 1989 and 1995 were followed for 5 years and repeatedly
      interviewed about illicit ("hard")--drug use. Up to 3 periodic urine screens
      validated self-reported use. Outcomes were compared between hard-drug users
      (women using cocaine, heroin, methadone, or injecting drugs) and nonusers,
      adjusting for age, antiretroviral therapy, number of pregnancies, smoking, and
      baseline CD4 cell percentage. Of 1148 women, 40% reported baseline hard-drug use
      during pregnancy. In multivariate analyses, hard-drug use was not associated with
      change in CD4 cell percentage (P = 0.84), HIV RNA level (P = 0.48), or all-cause
      mortality (relative hazard = 1.10; 95% confidence interval, 0.61-1.98). Hard-drug
      users did, however, exhibit a higher risk of developing class C diagnoses
      (relative hazard = 1.65; 95% confidence interval, 1.00-2.72), especially herpes,
      pulmonary tuberculosis, and recurrent pneumonia. Hard-drug-using women may have a
      higher risk for nonfatal opportunistic infections.

PMID- 15483473
TI  - Dexamethasone downregulates Cryptococcus neoformans-induced vascular endothelial
      growth factor production: a role for corticosteroids in cryptococcal meningitis?

PMID- 15483474
TI  - Platelets may affect detection and quantitation of HIV RNA in plasma samples with
      low viral loads.

PMID- 15483476
TI  - Evolving guidelines for intravitreous injections.
AB  - Intravitreous (i.v.t.) injection is increasingly being incorporated into the
      management of ocular diseases. While only fomivirsen sodium (Vitravene) is
      currently approved by the Food and Drug Administration as an i.v.t. injection,
      the number of approved i.v.t. injections indications is anticipated to grow on
      the basis of promising results from ongoing clinical studies. Despite the
      potential benefits that may be derived from intraocular injections of different
      agents, no guidelines have been published previously for i.v.t. injection. The
      purpose of this document is to identify specific strategies for the delivery of
      i.v.t. injection that may reduce risks and improve outcomes. Consensus was sought
      among a panel of investigators, surgeons experienced with this technique, and
      industry representatives. Objective evidence was sought for all guidelines, but
      consensus was accepted where evidence remains incomplete. In the absence of
      either evidence or consensus, the current manuscript identifies outstanding
      issues in need of further investigation. It is anticipated that more complete
      guidelines will evolve over time, potentially altering some of the guidelines
      included here, based on new applications of i.v.t. injection, additional clinical
      experience, and results of clinical trials.

PMID- 15483477
TI  - Providing optimal preoperative localization for recurrent parathyroid carcinoma:
      a combined parathyroid scintigraphy and computed tomography approach.
AB  - PURPOSE: The incidence of parathyroid carcinoma is approximately 0.5% to 5% in
      patients with primary hyperparathyroidism. Recurrent parathyroid carcinoma is
      treated with surgical resection of all sites of disease to ameliorate systemic
      manifestations of hyperparathyroidism, primarily hypercalcemia. This study
      investigates the role of parathyroid scintigraphy and computed tomography (CT)
      imaging in recurrent parathyroid carcinoma. MATERIALS AND METHODS: A
      retrospective chart review was performed on 8 patients diagnosed with recurrent
      parathyroid carcinoma at our tertiary care institution between 1975 and 2001.
      Surgical reports, histopathology, parathyroid scintigraphy, and CT findings were
      recorded. Surgical reports and radiologic studies were compared for concordance
      of recurrence sites. RESULTS: There were 32 imaging studies before reoperation:
      15 parathyroid scintigraphy and 17 CTs. Of 15 sites of recurrence potentially
      seen on scintigraphy, 10 were true-positive (67%). Of 17 sites of recurrence
      potentially seen on CT, 9 were true-positive (53%). Of the 8 false-negatives on
      CT, 7 of these recurrences were in the surgical bed (88%). There were 9 instances
      in which CT and scintigraphy were performed preoperatively for comparison and
      correlation. CT and scintigraphic findings were incongruent in 7 of 9 of these
      cases (78%). CONCLUSION: Successful surgical intervention for recurrent
      parathyroid carcinoma requires accurate preoperative localization studies and
      complete excision of metastases. Our data supports combined analysis of
      parathyroid scintigraphy and CT for patients with recurrent disease before
      reoperation. Additionally, our review suggests that sensitivity may be optimized
      with SPECT parathyroid scintigraphy and close correlation with CT.

PMID- 15483478
TI  - Spontaneous regression of follicular, mantle cell, and diffuse large B-cell non
      Hodgkin's lymphomas detected by FDG-PET imaging.
AB  - Spontaneous regression of non-Hodgkin lymphoma (NHL) has been reported in low
      grade tumors but is an extremely rare event in intermediate- and high-grade
      disease. Documentation of spontaneous regression by serial fluorodeoxyglucose
      positron emission tomography (FDG-PET) imaging has not been reported in the
      literature. We present 3 cases of spontaneous regression, 1 each of follicular
      lymphoma (FL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma
      (DLBCL), which showed spontaneous regression on serial FDG-PET imaging. All
      patients underwent serial whole-body FDG-PET scans 60 minutes after intravenous
      injection of 9-11 mCi of this radiotracer. None of them had any chemotherapy,
      radiotherapy, or surgery after the baseline PET scan. Spontaneous regression of
      disease in all 3 cases was correlated with conventional imaging and clinical
      course. All 3 patients had positive FDG-PET results on their baseline scan. There
      was complete disappearance of FDG uptake on a follow-up PET scan for the patient
      with follicular lymphoma. These results suggest complete regression. The patients
      with MCL and DLBCL both showed a significant reduction in FDG uptake on serial
      whole-body PET scans, suggesting partial regression in both cases. Although
      spontaneous regression of lymphoma is uncommon, this phenomenon can be
      successfully demonstrated by FDG-PET imaging. Therefore, serial PET imaging may
      play an important role in detecting this unusual event and may further enhance
      our understanding of the biologic behavior of this malignancy.

PMID- 15483479
TI  - Young athletes with low back pain: skeletal scintigraphy of conditions other than
      pars interarticularis stress.
AB  - PURPOSE: Skeletal scintigraphy is an important method for showing evidence of
      stress injuries affecting the partes interarticulares of young athletes with low
      back pain. Other etiologies of low back pain may also cause uptake abnormalities
      in these patients. How often do the results of skeletal scintigraphy support
      diagnoses other than stress injuries to the partes interarticulares and what are
      these diagnoses? MATERIALS AND METHODS: We retrospectively reviewed the records
      of 209 young patients (149 females, 60 males; age range: 8-21 years, mean: 15.7
      years) with low back pain and no previously treated vertebral condition who were
      consecutively referred from a sports medicine clinic to skeletal scintigraphy.
      RESULTS: Sites of high uptake supportive of diagnoses other than pars
      interarticularis stress were shown in 36 (17%) of the 209 patients. Other
      diagnoses supported by skeletal scintigraphy included stress at the articulation
      between a transitional vertebra and the sacrum, injuries to the vertebral body
      ring apophysis, sacral fracture, spinous process injury, and sacroiliac joint
      stress. CONCLUSION: Skeletal scintigraphy shows uptake abnormalities supportive
      of diagnoses other than pars interarticularis stress in a significant number of
      young patients with low back pain. The uptake abnormalities shown are usually
      stress-related in this select population.

PMID- 15483480
TI  - Two patients with abnormal skeletal muscle uptake of Tc-99m hydroxymethylene
      diphosphonate following liver transplant: nephrogenic fibrosing dermopathy and
      graft vs host disease.
AB  - Tc-99m hydroxymethylene disphosphonate administered for skeletal scintigraphy may
      be seen in the extraosseous tissues for various etiologies. This report presents
      similar abnormal lower extremity skeletal muscle uptake in 2 patients status
      postorthotopic liver transplant. Although the history and scintigraphic
      appearance of the 2 were similar, subtle differences in cutaneous lesions and
      histology led to disparate diagnoses.

PMID- 15483481
TI  - Alternative lymphatic pathway after previous axillary node dissection in
      recurrent/primary breast cancer.
AB  - OBJECTIVES: The sentinel lymph node approach has almost become the standard
      procedure of choice in the management of patients with early breast cancer. The
      status of sentinel nodes, whether or not pathologically involved by cancer cells,
      represents those of the axillary nodes with a negative predictive value of almost
      100%. If the axillary lymphatic nodal drainage is altered, alternative lymphatic
      pathways and accordingly sentinel node location will be changed. METHODS: In this
      article, 4 patients are presented, 3 with recurrent breast cancer who had already
      undergone lumpectomy, axillary node dissection, and radiotherapy in the past and
      1 with primary breast cancer after surgical removal of a malignant melanoma on
      her back and had axillary node dissection on the same side as the breast cancer.
      These patients underwent lymphoscintigraphy followed by sentinel node
      localization using the gamma probe and also blue dye injection during surgery.
      RESULTS: All patients showed alternate lymphatic pathways, 1 had an ipsilateral
      internal mammary node and crossed lymphatics to a contralateral axillary node, 2
      had intramammary sentinel nodes, and 1 had an internal mammary on the same side.
      Pathologic examination of the intramammary and contralateral sentinel nodes were
      negative for metastases. Internal mammary sentinel nodes were not biopsied.
      CONCLUSION: We feel that sentinel node lymphoscintigraphy should be done even in
      patients who have altered lymphatic pathways resulting from previous axillary
      node dissection. It allows identifying and biopsy of the sentinel node at its new
      unpredicted location.

PMID- 15483482
TI  - Periostitis and localized myositis in polyarteritis nodosa.

PMID- 15483483
TI  - Unusual bone scintigraphic findings of secondary myelofibrosis associated with
      disseminated tuberculosis before and after therapy.

PMID- 15483484
TI  - Vanishing bone disease of the pelvis.

PMID- 15483485
TI  - Long-term follow-up of a patient with McCune-Albright syndrome by whole-body bone
      scan and SPECT.

PMID- 15483486
TI  - Multimodality imaging in characterizing the metastases of multiple endocrine
      neoplasia type 2a.

PMID- 15483487
TI  - Perineural spread of skin carcinoma to the base of the skull: detection with FDG
      PET and CT fusion.

PMID- 15483488
TI  - Interesting presentation of renal and adjacent rib infection on bone
      scintigraphy: the additive value of tissue phase images.

PMID- 15483489
TI  - Tc-99m methylene diphosphonate uptake in a primary lung cancer.

PMID- 15483490
TI  - Myopathy associated with primary biliary cirrhosis demonstrating muscle
      involvement on bone scanning.

PMID- 15483491
TI  - Utility of very delayed parathyroid MIBI SPECT for localization of parathyroid
      adenoma.

PMID- 15483492
TI  - Enhanced detection of a parathyroid adenoma following radioiodine treatment of
      concurrent, toxic multinodular goiter.

PMID- 15483493
TI  - Incidental detection of an autonomous nodule in a retrosternal goiter on F-18 FDG
      positron emission tomography.

PMID- 15483494
TI  - "Disappearing" mediastinal parathyroid adenoma: retention at the tip of an
      intrathoracic catheter.

PMID- 15483495
TI  - Central line injection artifact simulating paratracheal adenopathy on FDG PET
      imaging.

PMID- 15483496
TI  - Unusual patterns of I-131 accumulation.

PMID- 15483497
TI  - Pericardial lymph node involvement in lymphoma as identified on PET.

PMID- 15483498
TI  - Pleomorphic adenoma simulating metastatic squamous cell carcinoma on f-18
      fluorodeoxyglucose positron emission tomography.

PMID- 15483499
TI  - Segmental contour mapping pattern in a patient with breast carcinoma.

PMID- 15483500
TI  - Identification of pelvic varices on gated cardiac imaging and hepatobiliary
      scans.

PMID- 15483501
TI  - F-18 FDG PET imaging features of a perigraft leak and thrombus in a patient with
      dissecting descending thoracic aortic aneurysm.

PMID- 15483502
TI  - Typical and atypical bronchopulmonary carcinoid tumors on FDG PET/CT imaging.

PMID- 15483503
TI  - Progressive massive fibrosis secondary to pulmonary silicosis appearance on F-18
      fluorodeoxyglucose PET/CT.

PMID- 15483504
TI  - Inhalation of crack cocaine can mimic pulmonary embolism.

PMID- 15483505
TI  - Detection of a pulmonary epithelioid hemangioendothelioma by FDG PET scan.

PMID- 15483507
TI  - Left-to-right cardiac shunt diagnosed on Tc-99m MAG-3 renal study.

PMID- 15483506
TI  - Acute pulmonary embolism due to hydatid cyst.

PMID- 15483508
TI  - Crossed fused renal ectopia with metastatic renal cell carcinoma.

PMID- 15483509
TI  - Bladder hernia simulating metastatic lesion on FDG PET study.

PMID- 15483510
TI  - Esophageal motor disorder diagnosed by esophageal transit scintigraphy.

PMID- 15483512
TI  - Current readings in nuclear medicine.

PMID- 15483511
TI  - Virchow's node on F-18 FDG PET/CT.

PMID- 15483524
TI  - Newborn screening for cystic fibrosis: evaluation of benefits and risks and
      recommendations for state newborn screening programs.
AB  - In November 2003, CDC and the Cystic Fibrosis Foundation cosponsored a workshop
      to review the benefits and risks associated with newborn screening for cystic
      fibrosis (CF). This report describes new research findings and outlines the
      recommendations of the workshop. The peer-reviewed evidence presented at the
      workshop supports the clinical utility of newborn screening for CF. Demonstrated
      long-term benefits from early nutritional treatment as a result of newborn
      screening for CF include improved growth and, in one study, cognitive
      development. Other benefits might include reduced hospitalizations and improved
      survival. Mixed evidence has been reported for pulmonary outcomes. Newborn
      screening in the United States is associated with diagnosis of CF a median of 1
      year earlier than symptomatic detection, which might reduce the expense and
      anxiety associated with workup for failure to thrive or other symptoms. Certain
      psychosocial risks for carrier children and their families (e.g., anxiety and
      misunderstanding) are associated with newborn screening. Exposure of young
      children to infectious agents through person-to-person transmission in clinical
      settings, although not an inherent risk of newborn screening, is a potential
      cause of harm from early detection. Involving specialists in CF care and
      infection control, genetic counseling, and communication can minimize these
      potential harms. Although screening decisions depend on a state's individual
      resources and priorities, on the basis of evidence of moderate benefits and low
      risk of harm, CDC believes that newborn screening for CF is justified. States
      should consider the magnitude of benefits and costs and the need to minimize
      risks through careful planning and implementation, including ongoing collection
      and evaluation of outcome data.

PMID- 15483525
TI  - Health disparities experienced by Hispanics--United States.
AB  - In the 2000 census, 35.3 million persons in the United States and 3.8 million
      persons in the Commonwealth of Puerto Rico identified themselves as Hispanic
      (i.e., Hispanic, Spanish, or Latino; of all races). Hispanics constituted 12.5%
      of the U.S. population in the 50 states; by subpopulation, they identified as
      Mexican (7.3%), Puerto Rican (1.2%), Cuban (0.4%), and other Hispanic (3.6%). For
      certain health conditions, Hispanics bear a disproportionate burden of disease,
      injury, death, and disability when compared with non-Hispanic whites, the largest
      racial/ethnic population in the United States. The leading causes of death among
      Hispanics vary from those for non-Hispanic whites. This week's MMWR is the second
      in a series focusing on racial/ethnic health disparities; eliminating these
      disparities will require culturally appropriate public health initiatives,
      community support, and equitable access to quality health care.

PMID- 15483526
TI  - Access to health-care and preventive services among Hispanics and non-Hispanics-
      United States, 2001-2002.
AB  - Although Hispanics are the largest ethnic minority population in the United
      States, they are underserved by the health-care system. Hispanics are less likely
      to seek and receive health-care services, which might contribute to their poorer
      health status and higher rates of morbidity and mortality. To assess differences
      in access to health-care and preventive services between Hispanics and non
      Hispanics, CDC analyzed 2001-2002 data from the Behavioral Risk Factor
      Surveillance System (BRFSS) surveys. This report summarizes the results of that
      analysis, which indicated that disparities exist in access to health-care and
      preventive services among Hispanics versus non-Hispanics. Public health
      authorities and health-care providers should implement strategies to reduce
      barriers to health-care and preventive services among Hispanics.

PMID- 15483527
TI  - Prevalence of diabetes among Hispanics--selected areas, 1998-2002.
AB  - Diabetes disproportionately affects Hispanics in the United States. However, the
      Hispanic population is composed of culturally distinct subpopulations that tend
      to be regionally concentrated, and the prevalence of diabetes can differ in these
      subpopulations. CDC analyzed data from Behavioral Risk Factor Surveillance System
      (BRFSS) surveys to estimate the prevalence of diabetes among Hispanic and non
      Hispanic white adults residing in six states and among Hispanics in Puerto Rico,
      assessing disparities by geographic location. This report summarizes the findings
      of that analysis, which indicated that Hispanics continued to have a higher
      prevalence of diabetes than non-Hispanic whites and that disparities in diabetes
      between these two populations varied by area of residence. These findings
      underscore the need to target Hispanics and other populations with higher
      prevalence of diabetes to eliminate racial/ethnic disparities.

PMID- 15483528
TI  - Assessment of increase in perinatal exposure to HIV among Hispanics--20 counties,
      Georgia, 1994-2002.
AB  - CDC recently received reports from clinicians in a specialized pediatric human
      immunodeficiency virus (HIV) care clinic (clinic A) suggesting that the number of
      perinatally HIV-exposed Hispanic infants in the Atlanta metropolitan area had
      increased disproportionately to the growth of Hispanics in the area's population.
      To assess this increase and characterize trends in perinatal HIV exposure in this
      population, CDC collaborated with health-care providers at clinic A, which serves
      residents in 20 Georgia counties, including the Atlanta metropolitan area. This
      report summarizes the results of that assessment, which suggest that the increase
      in the number of perinatally HIV-exposed Hispanic infants was associated with
      multiple factors, including the growth of the Hispanic population, increasing HIV
      prevalence and fertility among Hispanics, and lower preconception awareness of
      HIV serostatus among those with HIV. The findings suggest a need for improved
      access to voluntary HIV counseling and testing and increased opportunities for
      reducing the risk for unintended pregnancy among Hispanics in these counties.

PMID- 15483529
TI  - Effect of revised population counts on county-level Hispanic teen birthrates-
      United States, 1999.
AB  - In 2002, teen birthrates for Hispanics were higher than for all other
      racial/ethnic populations. Because of the health and social risks associated with
      teen births, pregnancy prevention programs and accurate surveillance of teen
      birthrates are critical. To assess the effect of using revised population
      estimates for the 1990s (intercensal estimates) that take into account both the
      1990 and 2000 U.S. Census counts, CDC analyzed county-level estimates of Hispanic
      teen birthrates for 1999. This report summarizes the results of that analysis,
      which indicated that Hispanic teen birthrates for 1999, when calculated on the
      basis of the 2000 census, were lower than birthrates based on the 1990 census for
      the majority of counties with substantial Hispanic populations. Population
      estimates for 1999 based on the 1990 census (postcensal estimates) had failed to
      capture the unprecedented and unanticipated migration of Hispanics, thereby
      overestimating the Hispanic teen birthrate. However, the increase in the Hispanic
      teen population and the corresponding decrease in Hispanic teen birthrates for
      1999 were not experienced by all counties. This county-level variation provides
      essential information for programs targeting Hispanic teens at the county level.

PMID- 15483530
TI  - West Nile virus activity--United States, October 6-12, 2004.
AB  - During October 6-12, a total of 86 cases of human West Nile virus (WNV) illness
      were reported from 18 states (Arizona, Florida, Illinois, Kansas, Louisiana,
      Michigan, Minnesota, Missouri, Nevada, New Jersey, New Mexico, North Dakota,
      Ohio, Oklahoma, Pennsylvania, Tennessee, Texas, and Utah).

PMID- 15483531
TI  - A new technique of graft harvest for anterior cruciate ligament reconstruction
      with quadruple semitendinosus tendon autograft.
AB  - A new technique of graft harvesting was used in 8 cases for arthroscopic anterior
      cruciate ligament reconstruction with quadruple semitendinosus tendon autograft.
      The graft is acquired through a small incision on the posteromedial aspect of the
      knee at the flexor crease instead of the standard anteromedial approach through a
      paramedian incision. Compared with the standard technique of graft harvesting,
      this new method of graft harvest facilitates easier identification of the
      semitendinosus and avoids inadvertent amputation of the semitendinosus tendon
      during graft harvest, disinsertion of the pes anserinus, or injury to the
      infrapatellar branch of saphenous nerve. The surgical scars, in addition to the
      standard portal scars, include a small scar on the posteromedial aspect, which
      merges into the flexor crease and a 1-cm anteromedial scar. This provides
      improved cosmesis and better patient compliance for early rehabilitation with
      less pain in the immediate postoperative period. There is no compromise on the
      intraoperative ligament reconstruction with good postoperative results. No
      intraoperative or postoperative complications were encountered. It would be
      advisable to follow this technique of graft harvesting for all individuals
      undergoing arthroscopic anterior cruciate ligament reconstruction using
      quadrupled semitendinosus tendon to avoid the problems encountered with the
      standard technique, and also to achieve an excellent cosmetic and functional
      outcome.

PMID- 15483532
TI  - Bursoscopic evaluation for degree of rotator cuff tear using an air-infusion
      method.
AB  - This article presents a method of bursoscopic examination with use of a
      glenohumeral air-infusion technique for the detection of full-thickness tears
      hidden by bursal tissue. We inflated the glenohumeral joint with 50 to 60 mL of
      air while simultaneously observing the joint with bursoscopy for the detection of
      air bubble leakage. The air-infusion technique is valuable in detecting full
      thickness tears and useful for evaluating the patency of repair.

PMID- 15483533
TI  - Fixation of greater tuberosity fractures.
AB  - The authors describe arthroscopic reduction and percutaneous fixation of greater
      tuberosity fractures of the humerus with displacement of more than 0.5 cm.
      Arthroscopy for reduction and fixation of this fracture presents the same
      difficulties and advantages as arthroscopic repair of rotator cuff tears.

PMID- 15483534
TI  - Multiple loose bodies in the joints: from snowstorm to hailstones.
AB  - We report the cases of 2 young-adult patients with multiple loose bodies, one in
      the knee and the other in the elbow joint. Loose bodies were composed of hundreds
      of brilliant white particles up to 5 mm in the first patient, who had a history
      of pain and swelling. From the right elbow joint of the second patient,
      arthroscopic removal of about 25 osteocartilaginous loose bodies, ranging from 5
      to 14 mm in diameter, was performed. This patient also had the effects of
      poliomyelitis, which had required him to use a crutch since childhood for right
      lower limb length discrepancy. Arthroscopic removal provided elimination of
      symptoms in both patients. Histopathologic examination of the specimens and
      clinical evidence supported the previously proposed pathogenic mechanisms on
      development of loose bodies. Mechanisms that could affect the natural history of
      loose bodies in these particular patients are discussed and speculated on in this
      report. We suggest that some of the numerous cartilaginous multiple loose bodies
      in the joints (snowstorm appearance) are attached and incorporated into synovium
      and the total number decreases with time, while the remaining grow with
      nutritional effects of synovial fluid medium, resulting in larger loose bodies
      with osteocartilaginous characteristics. The term "hailstone" is used to describe
      the ultimate situation of the previous arthroscopically defined snowstorm loose
      bodies.

PMID- 15483535
TI  - A simple device for inside-out meniscal suture.
AB  - In view of the negative consequences of the meniscectomy of the knee joint, there
      is a general consensus regarding the importance of conserving the menisci,
      especially when the injury occurs in the peripheral vascular zone, where the
      chances of healing are greater. In this report, we present a simple inside-out
      meniscal suture device in which a braided Nylon thread is inserted using a 2-mm
      needle with 1 or 2 holes in the tip (to accommodate 1 or 2 threads), piercing the
      soft tissue to carry out either a single or double suture, depending on the size
      of the meniscal lesion. The advantage of this device over other methods is that
      it facilitates access to the joint from any location, removing the need for
      accessory arthroscopic portals and thus enabling the injury to be approached more
      easily.

PMID- 15483536
TI  - Bilateral absence of the patella in nail-patella syndrome: delayed presentation
      with anterior knee instability.
AB  - A 27-year-old man, while serving in the armed forces, presented with complaints
      of right knee pain of 3 months duration. The patient reported pain localized on
      the lateral side of the right knee, especially during long-distance walking and
      stair climbing, and a feeling of giving way. There was no history of recent or
      remote trauma to the knee joint. At that time, he presented with knee pain and
      instability consistent with anterior cruciate ligament (ACL) insufficiency.
      During physical examination, the diagnosis of nail-patella syndrome (NPS) was
      made, but magnetic resonance imaging (MRI) of both knees revealed intact ACLs.
      The reported case presents NPS as a potential nontraumatic cause of anterior knee
      instability. In our patient, a discrepancy between the clinical and imaging
      findings was present. The initial clinical examination was consistent with ACL
      rupture or aplasia and this led to MRI evaluation of the knee, which showed an
      intact ACL, contrary to the initial diagnosis. It should be noted that anterior
      instability has been described after patellectomy and could be attributed to
      complete absence of the patella, which is rare in NPS.

PMID- 15483537
TI  - Lipoma arborescens of the knee.
AB  - Lipoma arborescens are rare lesions, typically located in the knee. They have a
      predilection for the suprapatellar pouch in the knee joint, but can also occur in
      any area of the knee joint. Magnetic resonance imaging of lipoma arborescens
      often reveals subchondral bone cyst and/or bone erosions, and there may appear to
      be a correlation between lipoma arborescens and osteoarthritis. We describe a
      case of histologically proven lipoma arborescens in the suprapatellar pouch and
      infrapatellar area of the knee with no damage to the posterior compartment and
      bone erosion in the proximal tibia without osteoarthritis.

PMID- 15483538
TI  - Revision anterior cruciate ligament reconstruction with nonirradiated fresh
      frozen patellar tendon allograft.
AB  - PURPOSE: To evaluate the effectiveness of a revision anterior cruciate ligament
      reconstruction with nonirradiated patellar tendon allograft used to salvage a
      failed index patellar tendon autograft procedure. TYPE OF STUDY: Retrospective
      case series with minimum 2-year follow-up. METHODS: Between 1993 and 1999, 39
      patients underwent a revision reconstruction. Clinical, radiographic,
      arthrometric, and functional evaluations were performed. The Tegner, Lysholm,
      Noyes, Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee
      Documentation Committee (IKDC), and SF-12 rating scales were used. Statistical
      analysis was conducted with our Biostatistics Department. RESULTS: Thirty-two of
      38 patients (84%) were personally evaluated. The mean patient age was 28 years
      (range, 16 to 57 years); the mean follow-up was 4.8 years (range, 2.1 to 12.1
      years). After revision, there were significant improvements in the Lachman and
      pivot-shift test results: 87% had a grade 0/1+ Lachman and a 0/1+ pivot-shift.
      However, 25% had a grade 1+ pivot-shift. Postoperatively, KT-1000 testing
      revealed that 84% had a maximum manual side-to-side difference of < or =3 mm and
      6% had >5 mm. Functional testing revealed a mean 4% difference in side-to-side
      comparisons for a single-leg hop for distance and time, as well as vertical jump.
      The mean results of Noyes sports function (72), Lysholm (75), Tegner (6.3), KOOS
      sports activity scale (67), SF-12 physical component (48), SF-12 mental component
      (55), and IKDC (71) were obtained. The Noyes sports activity score showed a
      significant improvement from 55 preoperatively to 70 at follow-up. Subjectively,
      87% of patients indicated that they were completely or mostly satisfied with the
      surgical outcome. One patient required another revision. CONCLUSIONS: The 2- to
      11-year follow-up showed that the results of revision ACL reconstruction with a
      nonirradiated patellar tendon allograft were less favorable than those of a
      primary anterior cruciate ligament reconstruction, with a lower subjective
      satisfaction level and a higher percentage of patients with grade 1+ or higher
      pivot-shift results. However, when compared with previously published reports,
      our results were comparable and underscore that revision anterior cruciate
      ligament surgery should be approached with tempered enthusiasm and careful
      preoperative counseling, and considered as a salvage procedure. LEVEL OF
      EVIDENCE: Level IV.

PMID- 15483539
TI  - Outcome of anterior cruciate ligament reconstruction using quadriceps tendon
      autograft.
AB  - PURPOSE: The purpose of this study was to determine the outcome of anterior
      cruciate ligament (ACL) reconstruction using a quadriceps tendon autograft. TYPE
      OF STUDY: A case series of patients who had received arthroscopic ACL
      reconstructions using quadriceps tendon autograft was retrospectively evaluated.
      METHODS: Sixty-seven ACL reconstructions were evaluated at a mean of 41 months
      (range, 27 to 49 months). Clinical assessment was made using a modified Lysholm
      score, documentation of International Knee Documentation Committee (IKDC), the
      anterior knee pain questionnaire of Shelbourne and Trumper, and by KT-2000
      arthrometric analysis. Isokinetic strength testing and radiographic assessments
      were also performed. RESULTS: Arthrometric analysis showed that 63 knees (94%)
      were graded A or B with a median laxity of 2 mm postoperatively. The Lysholm
      score improved postoperatively from 71 to 90 ( P < or = .05). Extension peak
      torque of the quadriceps muscle recovered to 82% and 89% of that of the
      contralateral knee at 180 degrees/second at 1 year and 2 years after surgery,
      respectively. The patellar position in terms of congruence angle and Insall
      Salvati ratio did not show any significant change. Only 4 patients complained of
      moderate pain on kneeling and 1 patient complained of harvest-site tenderness.
      CONCLUSIONS: ACL reconstruction using a quadriceps tendon autograft showed
      satisfactory results with reduced donor-site morbidities. The quadriceps tendon
      can be a reliable source of graft, and is comparable to bone-patellar tendon-bone
      or hamstring tendon in ACL reconstruction. LEVEL OF EVIDENCE: Level IV, Case
      Series (no, or historical, control group).

PMID- 15483540
TI  - Cruciate ligament avulsion fractures.
AB  - PURPOSE: The objective of this study was to assess the variability of cruciate
      avulsion fractures. TYPE OF STUDY: Retrospective observational study. METHODS:
      Standardized radiographs and computed tomography (CT) examinations were performed
      in 40 patients (31 male, 9 female; age range, 10 to 77 years) with cruciate
      avulsion fractures. RESULTS: The average age of patients with anterior cruciate
      ligament (ACL) avulsion fractures was 21.5 years and that of patients with
      posterior cruciate ligament (PCL) avulsion fractures was 42.9 years. Two basic
      patterns of avulsion fracture emerged. ACL fractures were either partial (62%)
      (with avulsion of anteromedial bundle) or extended (38%) and were comminuted in
      25%. PCL fractures were either complete (47%) or extended (53%) and were
      comminuted in 50%. CT helped delineate fracture margins, comminution and extent.
      CONCLUSIONS: Although there is considerable variability in fracture type, 2 basic
      patterns of ACL and PCL avulsion fractures exist. CT helps delineate these
      features as a prelude to surgical fixation. LEVEL OF EVIDENCE: Level III.

PMID- 15483541
TI  - Efficacy of rofecoxib for pain control after knee arthroscopy: a prospective,
      randomized, double-blinded clinical trial.
AB  - PURPOSE: To determine if rofecoxib 50 mg administered 1 hour preoperatively to
      patients undergoing arthroscopic knee surgery reduces postoperative pain,
      provides a narcotic-sparing effect, and reduces time spent in recovery. TYPE OF
      STUDY: Prospective, randomized, double-blinded clinical trial. METHODS: Fifty
      patients (age range, 30 to 60 years) undergoing knee arthroscopy under spinal
      anesthesia were randomized to receive either 50 mg of rofecoxib or placebo 1 hour
      preoperatively. Postoperatively, pain was assessed in recovery, 8 hours
      postoperatively, and 24 hours postoperatively, using a 100-mm visual analog
      scale. Pain medication usage was monitored for 24 hours and time in recovery room
      was determined. Mann-Whitney tests determined significance between groups.
      RESULTS: Patients in the rofecoxib group showed significantly lower pain scores
      at 8 and 24 hours postoperatively. They also showed a significant reduction in
      postoperative narcotic consumption. CONCLUSIONS: Rofecoxib 50 mg as a single
      preoperative dose should be considered as part of a perioperative analgesic plan
      in arthroscopic knee surgery. LEVEL OF EVIDENCE: Level I, Therapeutic Study
      (randomized controlled trial).

PMID- 15483542
TI  - Italian version of the International Knee Documentation Committee Subjective Knee
      Form: cross-cultural adaptation and validation.
AB  - PURPOSE: Patient-oriented measures, represented by self-administered
      questionnaires, have become an important aspect of clinical outcome assessment.
      To be used with different language groups and in different countries,
      questionnaires must be translated and adapted to new cultural characteristics,
      and then validated by a widely accepted process to evaluate reliability and
      validity, fundamental characteristics for each measure. The aim of the study was
      to perform the cross-cultural adaptation and to assess the reliability and
      validity of the Italian version of the International Knee Documentation Committee
      (IKDC) Subjective Knee Form. TYPE OF STUDY: A cross-cultural adaptation and cross
      sectional study of a sample of patients undergoing anterior cruciate ligament
      (ACL) reconstruction with a subsample followed up prospectively for retest
      reliability. METHODS: The IKDC Subjective Knee Form was culturally adapted for
      Italian-speaking people, following the simplified Guillemin criteria. Reliability
      and validity were assessed in a cross-sectional study of 50 consecutive patients
      undergoing ACL reconstruction. A subsample of 20 patients was followed up
      prospectively for retest reliability. RESULTS: The results were compared with
      other validated patient-oriented measures. The principal IKDC scale showed a high
      correlation with other patient-oriented measures as hypothesized, and it also
      showed good values with regard to reproducibility, consistency, and validity,
      compared with the versions of IKDC published in other languages. CONCLUSIONS:
      These findings suggest that the evaluation capacities of the IKDC Italian version
      are equivalent to those of other language versions of the IKDC. LEVEL OF
      EVIDENCE: Level II.

PMID- 15483543
TI  - Sutureless avascular meniscal repair with a photoactive naphthalimide compound: a
      preliminary animal study.
AB  - PURPOSE: The purpose of this study was to evaluate the ability of 2 new
      photoactive naphthalimide compounds to repair a lesion in the avascular zone of
      the meniscus. TYPE OF STUDY: In vivo animal study. METHODS: Ten Barbados sheep
      were used as the animal model. Under anesthesia, the left knee joint was opened
      and 2 identical lesions were produced in the avascular zone of the medial
      meniscus. The posterior horn lesion was left alone and used as the control and
      the lesion in the anterior horn was repaired using the photoactive laser
      technique. The photoactive laser technique involved placing small amounts of a
      naphthalimide compound into the lesion and then irradiating the site with a laser
      (457 nm and 1.8 W/cm2) for 6 minutes. Two different versions of the naphthalimide
      compound were produced and divided between the 10 animals. The joint was then
      flushed with normal saline and closed in layers with resorbable sutures. Four
      animals were euthanized at the end of 1 month and 6 animals were euthanized at
      the end of 3 months. After death, the medial meniscus was exposed, dissected
      free, and then placed in 10% buffered formalin for histologic preparation and
      staining. RESULTS: At 1 month, the control lesions grossly showed no repair and
      the photochemically repaired lesions appeared to be bonded. The photochemically
      repaired lesions showed some bridging by an eosinophilic amorphous-appearing
      substance. The previous cleft within the fibrocartilaginous structure had
      disappeared, and early formation of connective tissue fibers was identified.
      However, some reduction in cellularity was seen in these tissue sections. At 3
      months, again the control lesions did not show any repair response, while the
      photochemically repaired lesions showed results similar to the animals at 1
      month, but with a less consistent pattern of tissue bonding and remodeling. The
      reduced tissue cellularity was still noted. There was no discernible difference
      between the naphthalimide compounds. CONCLUSIONS: These preliminary results
      demonstrate the potential usefulness of this photochemical bonding for the
      treatment of avascular meniscal lesions. Additional research will be necessary to
      fully understand the mechanism of this repair and optimize its use before any
      human trials. CLINICAL RELEVANCE: This is a preliminary animal study
      investigating the short-term in vivo effects of a novel photochemical compound
      for the repair of meniscal lesions. This repair may someday be valuable in the
      repair of avascular meniscal lesions.

PMID- 15483544
TI  - Arthroscopic treatment of 105 lateral meniscal cysts with 5-year average follow
      up.
AB  - PURPOSE: To evaluate meniscal damage and the midterm clinical outcome, we
      performed a retrospective review of 105 lateral meniscal cysts that were treated
      arthroscopically at our institution. TYPE OF STUDY: Retrospective review.
      METHODS: From a series of 8,100 knee arthroscopies, 122 patients (1.5%) with 124
      lateral meniscal cysts were selected. Eight of the patients were lost to follow
      up and 11 patients had associated pathology; therefore, 105 lateral meniscal
      cysts on stable knees were included in this study. Average follow-up was 5 years
      (range, 1 to 12.5 years). The mean age was 33 years (range, 12 to 69 years). All
      patients had presented with tenderness over the joint line with a palpable mass.
      All cases were treated arthroscopically and all patients underwent a complete
      physical examination before surgery and at last follow-up. Radiographic
      evaluation was available at final follow-up for 68 cases. RESULTS: All patients
      had a meniscal tear at the time of surgery and 60 (57%) had a horizontal cleavage
      component. For meniscal tears, arthroscopic partial lateral meniscectomy was
      performed in 104 cases and meniscal repair in 1 case. For cysts, intra-articular
      debridement was performed in 91 cases and open cystectomy in 14. Eleven cysts
      recurred and a second arthroscopy was required. The clinical results, including
      those cases with recurrent cysts, were excellent or good in 87% of cases.
      Osteoarthritis following treatment for meniscal cysts occurred in 9% of cases.
      CONCLUSIONS: When there was a cyst and no other intra-articular damage, the
      prognosis was excellent. For lateral meniscal cysts, arthroscopic partial
      meniscectomy with intra-articular debridement yields predictable results. LEVEL
      OF EVIDENCE: Level IV.

PMID- 15483545
TI  - The effect of graft sizing on osteochondral transplantation.
AB  - PURPOSE: The goal of this study was to analyze the effect of graft sizing on the
      histologic property of articular cartilage in autologous osteochondral
      transplantation. TYPE OF STUDY: Histologic analysis using an animal model.
      METHODS: Eighteen skeletally mature female Japanese white rabbits were used in
      this study and divided into 2 groups based on the surgical procedure. Group I: A
      cylindrical fragment (7 mm in diameter and 5 mm in depth) was harvested at the
      femoral condyle using the Osteochondral Autograft Transfer System (Arthrex,
      Naples, FL), then precisely returned to the defect from which the fragment was
      originally harvested. This surgical model supposes that the articular surface
      geometry of the osteochondral graft exactly matches that of the cartilage lesion;
      however, the osteochondral graft is not the same size as the defect in this model
      because of the surrounding gap that corresponds to the blade thickness of the
      chisel used to take the graft. Group II: A 1-mm larger osteochondral fragment (8
      mm in diameter and 5 mm in depth) taken from the contralateral femoral condyle
      was transplanted to the osteochondral defect made as in group I, achieving a
      tight fit. Specimens were stained with Safranin-O fast green and analyzed
      microscopically at 4, 12, and 24 weeks after surgery. RESULTS: In group I,
      histologic examination revealed an increase in cartilage thickness and cell
      density during the implantation period. Round and polygonal hypertrophic clusters
      of chondrocytes with cytoplasmic vacuoles were observed. By contrast, in group
      II, the thickness of the articular cartilage was almost the same as that of the
      normal adjacent cartilage with no significant change observed. CONCLUSIONS: It is
      suggested that sizing of the implanted osteochondral fragment plays an important
      role in preserving the histologic properties of cartilage. CLINICAL RELEVANCE:
      This study suggests that osteochondral graft stability may influence the
      histologic properties of the repaired cartilage. It is preferable to implant the
      slightly oversized graft into the cartilage lesion in autologous osteochondral
      transplantation to preserve the histologic properties of cartilage.

PMID- 15483546
TI  - Endoscopic carpal tunnel release using a new median nerve protector.
AB  - PURPOSE: We designed a reusable median nerve protector for endoscopic carpal
      tunnel release (ECTR) and prospectively evaluated its safety and efficacy. TYPE
      OF STUDY: Therapeutic study--Investigating the results of treatment. METHODS:
      Seventy-two patients (97 palms) with carpal tunnel syndrome were operated on
      endoscopically with the new median nerve protector. Patients were followed-up at
      1, 3, 6, 12, and 24 weeks postoperatively. Evaluation included the symptom
      severity scale, functional status scale, wound pain and scar tenderness,
      monofilament sensory mapping, grip strength measurement, and pin strength gauge.
      RESULTS: No patients sustained iatrogenic neurovascular injury or hematoma, but 3
      developed superficial wound infections postoperatively. The symptom severity
      score decreased from 3.8 points preoperatively to 2.3 at 1 week, 1.9 at 3 weeks,
      and 1.3 at 6 weeks, and remained at 1 point at 12 and 24 weeks postoperatively.
      The functional status score dropped from 3.8 points to 2.8 at 1 week, 2 at 3
      weeks, 1.5 at 6 weeks, and 1 at 12 weeks and thereafter. Semmes Weinstein
      monofilament mapping improved in all operated hands (59) of the 44 patients not
      lost to follow-up by 24 weeks. Tip pinch testing and grip strength showed gradual
      improvement as early as 3 weeks postoperatively. The mean value of the
      postoperative scar tenderness score dropped from 2.4 points at 1 week to 1.7
      points at 3 weeks, 1.3 at 6 weeks, 1.2 at 12 weeks, and 1 point after 12 weeks.
      CONCLUSIONS: This new median nerve protector provides clear visualization of
      neurovascular structures and is a safe and reliable tool for single-portal ECTR.
      LEVEL OF EVIDENCE: Level IV.

PMID- 15483547
TI  - Endoscopic release for carpal tunnel syndrome accompanied by thenar muscle
      atrophy.
AB  - PURPOSE: The objective of this study was to ascertain whether endoscopic carpal
      tunnel release (ECTR) is indicated for treatment of carpal tunnel syndrome
      accompanied by thenar muscle atrophy. TYPE OF STUDY: Prospective cohort study.
      METHODS: Two-portal ECTR was performed on 67 hands in 52 patients with carpal
      tunnel syndrome accompanied by thenar muscle atrophy. RESULTS: Preoperative
      severity of thenar muscle atrophy was severe in 24 hands, moderate in 23 hands,
      and mild in 20 hands. Postoperative severity of thenar muscle atrophy was severe
      in 6 hands, moderate in 2 hands, mild in 23 hands, and none in 36 hands.
      CONCLUSIONS: Improvements with thenar muscle function in most cases of carpal
      tunnel syndrome can be expected with 2-portal ECTR. LEVEL OF EVIDENCE: Level IV.

PMID- 15483548
TI  - Meniscal allograft transplantation--part II: alternative treatments, effects on
      articular cartilage, and future directions.
AB  - Abstract Meniscal allograft transplantation in clinical practice has progressed
      to a point where short-term relief of pain may be expected. However, it remains
      to be established whether a transplanted meniscus can prevent degenerative
      changes in the knee joint in the long term. In part II of this Current Concepts
      review, meniscus regeneration and alternative treatments to meniscal allograft
      transplantation are evaluated as well as the effect of meniscal allograft
      transplantation on articular cartilage. Remaining questions and future directions
      are considered in a final discussion. It can be concluded that considerably more
      data and evaluations of results are needed to determine whether meniscal
      allograft transplantation in humans will be successful in protecting and
      preserving articular cartilage after meniscectomy in the long term.

PMID- 15483549
TI  - Spontaneous rupture of the popliteus tendon in a 74-year-old woman and review of
      the literature.
AB  - Spontaneous rupture of the popliteus tendon has not previously been reported. We
      report the case of a 74-year-old patient, discuss its diagnosis and management,
      and review the current literature on isolated popliteus lesions. A multi-database
      electronic literature review suggests that the injury is invariably traumatic and
      has essentially been reported only in young, active individuals. It should be
      suspected in a patient with acute lateral knee pain who, on examination, has a
      hemarthrosis and a stable, possibly locked knee. The diagnosis is readily made
      using arthroscopy. While both conservative treatment with physiotherapy and open
      repair have been advocated, we describe a successful outcome of arthroscopic
      resection in an elderly patient and propose that popliteus injury is not confined
      to a younger age group. The balance of opinion in the current literature is that
      acute traumatic rupture in the young patient is managed by primary surgical
      repair, but successful outcome is also reported with nonoperative treatment.

PMID- 15483550
TI  - Monarthritis of the pediatric knee joint: differential diagnosis after a thorn
      injury.
AB  - Foreign-body injury of the juvenile knee is frequently seen in the outpatient
      department. Arthroscopy is the most important diagnostic and therapeutic
      procedure along with radiographic examination in a case of typical history and
      clinical symptoms. In this case, an intra-articular thorn in a juvenile knee was
      not diagnosed at arthroscopy despite typical injury. Five months later, the boy
      developed knee pain and joint swelling. Bacterial infection of the knee and
      rheumatoid causes were excluded by serologic blood analysis several times at the
      children's hospital. Magnetic resonance imaging of the knee revealed an intra
      articular foreign body. At a second arthroscopy, the thorn was removed and a
      hypertrophic plica with dependent cartilage damage of the medial femoral condyle
      was resected. At follow-up after 4 weeks, the boy was free of pain and swelling.
      After the first arthroscopy, persistent knee swelling and pain had to be taken as
      a hint of an intra-articular irritation. All arthroscopic surgeons should do a
      complete diagnostic examination of the affected joint in case of a foreign-body
      injury.

PMID- 15483551
TI  - Generation of meniscal cyst after arthroscopic meniscal repair.
AB  - Meniscal cyst is a common condition and it has been suggested that the
      degeneration of the meniscus may be largely associated with the occurrence of a
      meniscal cyst. However, meniscal cysts forming after meniscal repair are
      exceedingly rare. Previous reports have suggested that meniscal cyst after
      meniscal repair can be attributed to the cystic degeneration of the meniscus and
      the thread used for the meniscal suture. In this report, the developmental
      mechanism of a meniscal cyst after meniscal repair suturing is discussed.

PMID- 15483552
TI  - Avulsion of the superior labrum.
AB  - Snyder et al. coined the term superior labral anterior and posterior (SLAP)
      lesion and classified SLAP lesion into 4 types. Morgan et al. developed a
      secondary classification of Snyder type II lesions based on the anatomic
      location. Maffet et al. found that some lesions could not be classified according
      to classification of Snyder et al.; types V to VII were added to the 4-part
      classification. In this study, we present the case of a patient with a superior
      labral tear that could not be classified to any of the reported classification.
      The superior labrum was detached with cartilage exposing the underlying bone of
      the glenoid.

PMID- 15483553
TI  - Mattress double anchor footprint repair: a novel, arthroscopic rotator cuff
      repair technique.
AB  - In an effort to increase the immediate strength of a rotator cuff repair and to
      simulate the standard open reconstruction with its effective suture fixation, we
      have developed a novel technique for suture anchor reconstruction of the rotator
      cuff. The technique, termed mattress double anchor (MDA), is simple and
      adaptable. It makes use of 2 suture anchors that are placed independently and
      then connected by a suture loop. The technique produces a repair construct that
      distributes the stress across 2 anchors. The method also restores a large surface
      area for healing between the rotator cuff and the tuberosity.

PMID- 15483554
TI  - A new soft transglenoidal suture anchor for arthroscopic labrum fixation.
AB  - Inherent in most transglenoidal suture stabilization techniques of unstable
      shoulders is the unreliable fixation of posterior knots on the fascia. The
      transglenoidal suture anchor (TSA) technique overcomes this disadvantage. The TSA
      is a 1.5-cm loop of a No. 3 braided polyester thread with 5 knots. The loop is
      loaded with 1 or 2 sutures. Using a transglenoidal shuttle suture, it is pulled
      into a transglenoidal drill hole from the back in a retrograde fashion. The
      anchor is stopped at the posterior cortex of the glenoid by the knot. Using an
      arthroscopic suture passer technique (Bird Beak; Arthrex, Naples, FL) sutures are
      applied in the anterior-inferior part of the capsule, tied with a self-locking
      sliding knot, and secured with 2 or 3 additional throws. Two or 3 TSAs with 1 or
      2 threads per anchor are used in most cases. The ultimate failure load of 10
      samples of the anchor was tested with porcine scapulae. It was more than 156 N in
      every case. This technique enables the surgeon to use up to 4 anchors in the
      unstable shoulder with 1 or 2 sutures per anchor. The anchors are inexpensive. No
      problems are encountered in case of revision. There is no abrasion in the eyelet
      of the anchor as with metallic anchors and no synovitis as with some absorbable
      anchors.

PMID- 15483555
TI  - Minimally invasive surgery-total knee arthroplasty.
AB  - Minimally invasive surgery-total knee arthroplasty (MIS-TKA) requires a skin
      incision of < or =5 inches (measured with the knee in full extension). A mini
      midvastus approach limits surgical dissection and resultant soft tissue trauma.
      The patella is subluxated laterally but not everted . MIS-TKA is technically
      challenging and instrument dependent. The design of cutting guides, sizers, and
      retractors must continue to evolve. Prospective, randomized controlled trials are
      required to test the hypothesis that MIS-TKA results in decreased patient
      morbidity and outcome equal to or better than traditional TKA. The purpose of
      this article is to describe the MIS-TKA technique.

PMID- 15483556
TI  - Double-stranded hamstring graft for anterior cruciate ligament reconstruction.
AB  - Current techniques for anterior cruciate ligament (ACL) reconstruction do not
      completely reproduce the anatomy and function of the ACL. They address only the
      anteromedial bundle and do not fully restore ACL function throughout the range of
      motion. Current grafts control anterior tibial subluxation near extension, but
      are less efficacious in providing rotatory stability. Recently, several authors
      have suggested reconstructing not just the anteromedial bundle but also the
      posterolateral bundle. This technical note describes a double-bundle ACL
      reconstruction using hamstring tendons routed through 2 tibial and 2 femoral
      independent tunnels.

PMID- 15483557
TI  - Spontaneous osteonecrosis of the knee (SONK) developing as a possible consequence
      of the use of radiofrequency is misleading and illogical.

PMID- 15483558
TI  - TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate
      hair cells.
AB  - Mechanical deflection of the sensory hair bundles of receptor cells in the inner
      ear causes ion channels located at the tips of the bundle to open, thereby
      initiating the perception of sound. Although some protein constituents of the
      transduction apparatus are known, the mechanically gated transduction channels
      have not been identified in higher vertebrates. Here, we investigate TRP
      (transient receptor potential) ion channels as candidates and find one, TRPA1
      (also known as ANKTM1), that meets criteria for the transduction channel. The
      appearance of TRPA1 messenger RNA expression in hair cell epithelia coincides
      developmentally with the onset of mechanosensitivity. Antibodies to TRPA1 label
      hair bundles, especially at their tips, and tip labelling disappears when the
      transduction apparatus is chemically disrupted. Inhibition of TRPA1 protein
      expression in zebrafish and mouse inner ears inhibits receptor cell function, as
      assessed with electrical recording and with accumulation of a channel-permeant
      fluorescent dye. TRPA1 is probably a component of the transduction channel
      itself.

PMID- 15483559
TI  - The role of the dorsomedial prefrontal cortex, basolateral amygdala, and dorsal
      hippocampus in contextual reinstatement of cocaine seeking in rats.
AB  - The present study tested the hypothesis that separate neural substrates mediate
      cocaine relapse elicited by drug-associated contextual stimuli vs explicit
      conditioned stimuli (CSs) and cocaine. Specifically, we investigated the
      involvement of the dorsal hippocampus (DH), basolateral amygdala (BLA), and
      dorsomedial prefrontal cortex (dmPFC) in contextual reinstatement of cocaine
      seeking behavior and the involvement of the DH in explicit CS- and cocaine
      induced reinstatement. Rats were trained to self-administer cocaine in a distinct
      context or in the presence of CSs paired explicitly with cocaine infusions.
      Responding of context-trained rats was then extinguished in the previously
      cocaine-paired or an alternate context, whereas responding of explicit CS-trained
      rats was extinguished in the absence of the CSs. Subsequently, the target brain
      regions or anatomical control regions were functionally inactivated using
      tetrodotoxin (0 or 5 ng/side), and cocaine-seeking behavior (ie, nonreinforced
      responses) was assessed in the cocaine-paired context, in the alternate context,
      in the presence of the explicit CSs, or following cocaine priming (10 mg/kg,
      i.p.). DH inactivation abolished contextual, but failed to alter explicit CS- or
      cocaine-induced, reinstatement of cocaine-seeking behavior. BLA or dmPFC
      inactivation also abolished contextual reinstatement. Conversely, inactivation of
      the control brain regions failed to alter contextual reinstatement. In
      conclusion, the DH, BLA, and dmPFC play critical roles in contextual
      reinstatement. Previous findings suggest that the BLA is critical for explicit CS
      induced, but not cocaine-primed, reinstatement and the dmPFC is critical for both
      explicit CS-induced and cocaine-primed reinstatement. Thus, distinct but
      partially overlapping neural substrates mediate context-induced, explicit CS
      induced, and cocaine-primed reinstatement of extinguished cocaine-seeking
      behavior.

PMID- 15483560
TI  - Association of serotonin 5-HT2A receptor binding and the T102C polymorphism in
      depressed and healthy Caucasian subjects.
AB  - Serotonin 5-HT2A receptor (5-HT2A) binding is reported to be altered in
      individuals with suicidal behavior, mood disorders, and aggressive-impulsive
      traits. Genetic association with major depression, suicidal behavior, and
      aggressive-impulsive traits has not been established. This study examines the
      possible association of the 5-HT2A gene C102T polymorphism with the receptor
      binding kinetics, and clinical overt phenotypes. The study population included 63
      healthy volunteers and 152 subjects with mood disorders, 56 of whom had a history
      of suicide attempts. All were Caucasian. Platelet 5-HT2A binding kinetics (Bmax
      and KD) were assayed and adjusted for seasonal variation. All subjects were
      genotyped for the T102C polymorphism. Clinical phenotype was determined by
      structured clinical interview. The TT genotype was associated with higher Bmax in
      all subjects (F=3.53, df=2,211; p=0.03), controlling for diagnosis. Bonferroni
      adjusted post hoc testing showed higher binding in the TT compared with TC
      genotype in the control group (F=7.56, df=2,60, p=0.001), but not in the mood
      disordered subjects. No difference was found in genotype and allele distribution
      between the mood-disordered subjects, with and without suicide attempt history,
      and controls. Bmax was not related to a diagnosis of mood disorders. The TT
      genotype appears associated with higher platelet 5-HT2A Bmax in the healthy
      population, but this genotypic effect appears absent in mood disorders and
      unrelated to psychopathology.

PMID- 15483561
TI  - Modeling human methamphetamine exposure in nonhuman primates: chronic dosing in
      the rhesus macaque leads to behavioral and physiological abnormalities.
AB  - Acute high dose methamphetamine (METH) dosing regimens are frequently used in
      animal studies, however, these regimens can lead to considerable toxicity and
      even death in experimental animals. Acute high dosing regimens are quite distinct
      from the chronic usage patterns found in many human METH abusers. Furthermore,
      such doses, especially in nonhuman primates, can result in unexpected death,
      which is unacceptable, especially when such deaths fail to accurately model
      effects of human usage. As a model of chronic human METH abuse we have developed
      a nonlethal chronic METH administration procedure for the rhesus macaque that
      utilizes an escalating dose protocol. This protocol slowly increases the METH
      dosage from 0.1 to 0.7 mg/kg b.i.d. over a period of 4 weeks, followed by a
      period of chronic METH administration at 0.75 mg/kg b.i.d. (= total daily METH
      administration of 1.5 mg/kg). In parallel to human usage patterns, METH
      injections were given 20-23 times a month. This regimen produced a number of
      behavioral and physiological effects including decreased food intake and a
      significant increase in urinary cortisol excretion.

PMID- 15483562
TI  - Specific effects of an amnesic drug: effect of lorazepam on study time allocation
      and on judgment of learning.
AB  - We investigated the effects of lorazepam, a benzodiazepine, on the allocation of
      study time, memory, and judgment of learning, in a cognitive task where the
      repetition of word presentation was manipulated. The aim was to assess whether
      lorazepam would affect the learning processes and/or whether the participants
      would be aware of the amnesic difficulty. A total of 30 healthy volunteers
      participated in the study, 15 of whom received a capsule containing the lorazepam
      drug (0.038 mg/kg) and 15 a placebo capsule. First, the accuracy of delayed
      judgments of learning (JOL) was measured in both groups. For the JOL ratings,
      results showed that all the participants benefited from word repetition. Although
      the overall performance was lower in the lorazepam than in the placebo group, the
      accuracy of the JOL ratings was preserved by the drug. Second, all the
      participants benefited from the repetition of learning, although the performances
      of the lorazepam-treated subjects remained lower than those of the placebo
      participants. The repetition of learning had an effect on JOL in both groups.
      Finally, the time spent learning each (allocation study time) pair of words was
      measured. For the placebo group, results revealed that study time decreased
      significantly with the frequency of presentation. For the lorazepam group, no
      effect of presentation frequency was found. Overall, our findings suggest that
      the lorazepam drug has a differential effect on the monitoring and the control
      processes involved in a learning task. The implications of these findings are
      discussed within the theoretical framework of metacognition.

PMID- 15483564
TI  - Against grade inflation.

PMID- 15483563
TI  - Serotonin 1A receptor binding and treatment response in late-life depression.
AB  - Depression in late life carries an increased risk of dementia and brittle
      response to treatment. There is growing evidence to support a key role of the
      serotonin type 1A (5-HT(1A)) receptor as a regulator of treatment response,
      particularly the 5-HT(1A) autoreceptor in the dorsal raphe nucleus (DRN). We used
      [11C]WAY 100635 and positron emission tomography (PET) to test our hypothesis
      that 5-HT(1A) receptor binding in the DRN and prefrontal cortex is altered in
      elderly depressives and that these measures relate to treatment responsivity. We
      studied 17 elderly subjects with untreated (nonpsychotic, nonbipolar) major
      depression (four men, 13 women; mean age: 71.4+/-5.9) and 17 healthy control
      subjects (eight men, nine women; mean age: 70.0+/-6.7). Patients were
      subsequently treated with paroxetine as part of a clinical trial of maintenance
      therapies in geriatric depression. [11C]WAY 100635 PET imaging was acquired and
      binding potential (BP) values derived using compartmental modeling. We observed
      significantly diminished [11C]WAY 100635 binding in the DRN in depressed (BP =
      2.31+/-0.90) relative to control (BP = 3.69+/-1.56) subjects (p = 0.0016).
      Further, the DRN BP was correlated with pretreatment Hamilton Depression Rating
      Scores (r = 0.60, p = 0.014) in the depressed cohort. A trend level correlation
      between DRN binding and time to remission (r = 0.52, p = 0.067) was observed in
      the 14 depressed patients for whom these data were available. Our finding of
      decreased [11C]WAY 100635 binding in the brainstem region of the DRN in elderly
      depressed patients supports evidence of altered 5-HT(1A) autoreceptor function in
      depression. Further, this work indicates that dysfunction in autoreceptor
      activity may play a central role in the mechanisms underlying treatment response
      to selective serotonin reuptake inhibitors in late-life depression.

PMID- 15483565
TI  - California dreaming.

PMID- 15483566
TI  - Universities fear repercussions as NIH tunes conflicts policy.

PMID- 15483567
TI  - Californians up in arms over water assessment.

PMID- 15483568
TI  - US lacks back-up for flu vaccine shortfall.

PMID- 15483569
TI  - Canada to join 'big league' with its own science academy.

PMID- 15483570
TI  - Ukraine deluged by protests over plans for Danube delta.

PMID- 15483571
TI  - Paris collections snubbed in spending review.

PMID- 15483572
TI  - Advisers rebel over choice of museum chief.

PMID- 15483573
TI  - 'Memory of water' biologist dies after heart surgery.

PMID- 15483574
TI  - Chemistry Nobel for trio who revealed molecular death-tag.

PMID- 15483576
TI  - Antarctic stations: cold comfort.

PMID- 15483577
TI  - Formula 1 racing: science in the fast lane.

PMID- 15483578
TI  - Passion and politics cloud the climate debate.

PMID- 15483579
TI  - Climate: Russians face another disappointment.

PMID- 15483580
TI  - Best scientific advice is to read the climate report.

PMID- 15483585
TI  - Before the word.

PMID- 15483586
TI  - Neurodegenerative disease: neuron protection agency.

PMID- 15483587
TI  - Neutron halo slips.

PMID- 15483588
TI  - Optical fibres: a light fabric.

PMID- 15483589
TI  - Sunrise and sunset in fly brains.

PMID- 15483590
TI  - Accessing a transporter structure.

PMID- 15483592
TI  - Obituary: Jacques H. van Boom (1937-2004).

PMID- 15483594
TI  - Neurolinguistics: structural plasticity in the bilingual brain.
AB  - Humans have a unique ability to learn more than one language--a skill that is
      thought to be mediated by functional (rather than structural) plastic changes in
      the brain. Here we show that learning a second language increases the density of
      grey matter in the left inferior parietal cortex and that the degree of
      structural reorganization in this region is modulated by the proficiency attained
      and the age at acquisition. This relation between grey-matter density and
      performance may represent a general principle of brain organization.

PMID- 15483596
TI  - Computational roles for dopamine in behavioural control.
AB  - Neuromodulators such as dopamine have a central role in cognitive disorders. In
      the past decade, biological findings on dopamine function have been infused with
      concepts taken from computational theories of reinforcement learning. These more
      abstract approaches have now been applied to describe the biological algorithms
      at play in our brains when we form value judgements and make choices. The
      application of such quantitative models has opened up new fields, ripe for attack
      by young synthesizers and theoreticians.

PMID- 15483597
TI  - Generalization in vision and motor control.
AB  - Learning is more than memory. It is not simply the building of a look-up table of
      labelled images, or a phone-directory-like list of motor acts and the
      corresponding sequences of muscle activation. Central to learning and
      intelligence is the ability to predict, that is, to generalize to new situations,
      beyond the memory of specific examples. The key to generalization, in turn, is
      the architecture of the system, more than the rules of synaptic plasticity. We
      propose a specific architecture for generalization for both the motor and the
      visual systems, and argue for a canonical microcircuit underlying visual and
      motor learning.

PMID- 15483598
TI  - Neural networks and perceptual learning.
AB  - Sensory perception is a learned trait. The brain strategies we use to perceive
      the world are constantly modified by experience. With practice, we subconsciously
      become better at identifying familiar objects or distinguishing fine details in
      our environment. Current theoretical models simulate some properties of
      perceptual learning, but neglect the underlying cortical circuits. Future neural
      network models must incorporate the top-down alteration of cortical function by
      expectation or perceptual tasks. These newly found dynamic processes are
      challenging earlier views of static and feedforward processing of sensory
      information.

PMID- 15483599
TI  - Cortical rewiring and information storage.
AB  - Current thinking about long-term memory in the cortex is focused on changes in
      the strengths of connections between neurons. But ongoing structural plasticity
      in the adult brain, including synapse formation/elimination and remodelling of
      axons and dendrites, suggests that memory could also depend on learning-induced
      changes in the cortical 'wiring diagram'. Given that the cortex is sparsely
      connected, wiring plasticity could provide a substantial boost in storage
      capacity, although at a cost of more elaborate biological machinery and slower
      learning.

PMID- 15483600
TI  - Plasticity in single neuron and circuit computations.
AB  - Plasticity in neural circuits can result from alterations in synaptic strength or
      connectivity, as well as from changes in the excitability of the neurons
      themselves. To better understand the role of plasticity in the brain, we need to
      establish how brain circuits work and the kinds of computations that different
      circuit structures achieve. By linking theoretical and experimental studies, we
      are beginning to reveal the consequences of plasticity mechanisms for network
      dynamics, in both simple invertebrate circuits and the complex circuits of
      mammalian cerebral cortex.

PMID- 15483601
TI  - Synaptic computation.
AB  - Neurons are often considered to be the computational engines of the brain, with
      synapses acting solely as conveyers of information. But the diverse types of
      synaptic plasticity and the range of timescales over which they operate suggest
      that synapses have a more active role in information processing. Long-term
      changes in the transmission properties of synapses provide a physiological
      substrate for learning and memory, whereas short-term changes support a variety
      of computations. By expressing several forms of synaptic plasticity, a single
      neuron can convey an array of different signals to the neural circuit in which it
      operates.

PMID- 15483602
TI  - Inclusion body formation reduces levels of mutant huntingtin and the risk of
      neuronal death.
AB  - Huntington's disease is caused by an abnormal polyglutamine expansion within the
      protein huntingtin and is characterized by microscopic inclusion bodies of
      aggregated huntingtin and by the death of selected types of neuron. Whether
      inclusion bodies are pathogenic, incidental or a beneficial coping response is
      controversial. To resolve this issue we have developed an automated microscope
      that returns to precisely the same neuron after arbitrary intervals, even after
      cells have been removed from the microscope stage. Here we show, by survival
      analysis, that neurons die in a time-independent fashion but one that is
      dependent on mutant huntingtin dose and polyglutamine expansion; many neurons die
      without forming an inclusion body. Rather, the amount of diffuse intracellular
      huntingtin predicts whether and when inclusion body formation or death will
      occur. Surprisingly, inclusion body formation predicts improved survival and
      leads to decreased levels of mutant huntingtin elsewhere in a neuron. Thus,
      inclusion body formation can function as a coping response to toxic mutant
      huntingtin.

PMID- 15483603
TI  - Structure of a glutamate transporter homologue from Pyrococcus horikoshii.
AB  - Glutamate transporters are integral membrane proteins that catalyse the
      concentrative uptake of glutamate from the synapse to intracellular spaces by
      harnessing pre-existing ion gradients. In the central nervous system glutamate
      transporters are essential for normal development and function, and are
      implicated in stroke, epilepsy and neurodegenerative diseases. Here we present
      the crystal structure of a eukaryotic glutamate transporter homologue from
      Pyrococcus horikoshii. The transporter is a bowl-shaped trimer with a solvent
      filled extracellular basin extending halfway across the membrane bilayer. At the
      bottom of the basin are three independent binding sites, each cradled by two
      helical hairpins, reaching from opposite sides of the membrane. We propose that
      transport of glutamate is achieved by movements of the hairpins that allow
      alternating access to either side of the membrane.

PMID- 15483604
TI  - A fossil origin for the magnetic field in A stars and white dwarfs.
AB  - Some main-sequence stars of spectral type A are observed to have a strong (0.03-3
      tesla), static, large-scale magnetic field, of a chiefly dipolar shape: they are
      known as 'Ap stars', such as Alioth, the fifth star in the Big Dipper. Following
      the discovery of these fields, it was proposed that they are remnants of the
      star's formation, a 'fossil' field. An alternative suggestion is that they could
      be generated by a dynamo process in the star's convective core. The dynamo
      hypothesis, however, has difficulty explaining high field strengths and the
      observed lack of a correlation with rotation. The weakness of the fossil-field
      theory has been the absence of field configurations stable enough to survive in a
      star over its lifetime. Here we report numerical simulations that show that
      stable magnetic field configurations, with properties agreeing with those
      observed, can develop through evolution from arbitrary, unstable initial fields.
      The results are applicable equally to Ap stars, magnetic white dwarfs and some
      highly magnetized neutron stars known as magnetars. This establishes fossil
      fields as the natural, unifying explanation for the magnetism of all these stars.

PMID- 15483605
TI  - Jarosite as an indicator of water-limited chemical weathering on Mars.
AB  - The Mars Exploration Rover Opportunity identified the ferric sulphate mineral
      jarosite and possible relicts of gypsum at the Meridiani Planum landing site. On
      Earth, jarosite has been found to form in acid mine drainage environments, during
      the oxidation of sulphide minerals, and during alteration of volcanic rocks by
      acidic, sulphur-rich fluids near volcanic vents. Jarosite formation is thus
      thought to require a wet, oxidizing and acidic environment. But jarosite on Earth
      only persists over geologically relevant time periods in arid environments
      because it rapidly decomposes to produce ferric oxyhydroxides in more humid
      climates. Here we present equilibrium thermodynamic reaction-path simulations
      that constrain the range of possible conditions under which such aqueous
      alteration phases are likely to have formed on Mars. These calculations simulate
      the chemical weathering of basalt at relevant martian conditions. We conclude
      that the presence of jarosite combined with residual basalt at Meridiani Planum
      indicates that the alteration process did not proceed to completion, and that
      following jarosite formation, arid conditions must have prevailed.

PMID- 15483606
TI  - No enhancement of fusion probability by the neutron halo of 6He.
AB  - Quantum tunnelling through a potential barrier (such as occurs in nuclear fusion)
      is very sensitive to the detailed structure of the system and its intrinsic
      degrees of freedom. A strong increase of the fusion probability has been observed
      for heavy deformed nuclei. In light exotic nuclei such as 6He, 11Li and 11Be
      (termed 'halo' nuclei), the neutron matter extends much further than the usual
      nuclear interaction scale. However, understanding the effect of the neutron halo
      on fusion has been controversial--it could induce a large enhancement of fusion,
      but alternatively the weak binding energy of the nuclei could inhibit the
      process. Other reaction channels known as direct processes (usually negligible
      for ordinary nuclei) are also important: for example, a fragment of the halo
      nucleus could transfer to the target nucleus through a diminished potential
      barrier. Here we study the reactions of the halo nucleus 6He with a 238U target,
      at energies near the fusion barrier. Most of these reactions lead to fission of
      the system, which we use as an experimental signature to identify the
      contribution of the fusion and transfer channels to the total cross-section. At
      energies below the fusion barrier, we find no evidence for a substantial
      enhancement of fusion. Rather, the (large) fission yield is due to a two-neutron
      transfer reaction, with other direct processes possibly also involved.

PMID- 15483607
TI  - Metal-insulator-semiconductor optoelectronic fibres.
AB  - The combination of conductors, semiconductors and insulators with well-defined
      geometries and at prescribed length scales, while forming intimate interfaces, is
      essential in most functional electronic and optoelectronic devices. These are
      typically produced using a variety of elaborate wafer-based processes, which
      allow for small features, but are restricted to planar geometries and limited
      coverage area. In contrast, the technique of fibre drawing from a preformed reel
      or tube is simpler and yields extended lengths of highly uniform fibres with well
      controlled geometries and good optical transport characteristics. So far, this
      technique has been restricted to particular materials and larger features. Here
      we report on the design, fabrication and characterization of fibres made of
      conducting, semiconducting and insulating materials in intimate contact and in a
      variety of geometries. We demonstrate that this approach can be used to construct
      a tunable fibre photodetector comprising an amorphous semiconductor core
      contacted by metallic microwires, and surrounded by a cylindrical-shell resonant
      optical cavity. Such a fibre is sensitive to illumination along its entire length
      (tens of meters), thus forming a photodetecting element of dimensionality one. We
      also construct a grid of such fibres that can identify the location of an
      illumination point. The advantage of this type of photodetector array is that it
      needs a number of elements of only order N, in contrast to the conventional order
      N2 for detector arrays made of photodetecting elements of dimensionality zero.

PMID- 15483608
TI  - Control of ion selectivity in potassium channels by electrostatic and dynamic
      properties of carbonyl ligands.
AB  - Potassium channels are essential for maintaining a normal ionic balance across
      cell membranes. Central to this function is the ability of such channels to
      support transmembrane ion conduction at nearly diffusion-limited rates while
      discriminating for K+ over Na+ by more than a thousand-fold. This selectivity
      arises because the transfer of the K+ ion into the channel pore is energetically
      favoured, a feature commonly attributed to a structurally precise fit between the
      K+ ion and carbonyl groups lining the rigid and narrow pore. But proteins are
      relatively flexible structures that undergo rapid thermal atomic fluctuations
      larger than the small difference in ionic radius between K+ and Na+. Here we
      present molecular dynamics simulations for the potassium channel KcsA, which show
      that the carbonyl groups coordinating the ion in the narrow pore are indeed very
      dynamic ('liquid-like') and that their intrinsic electrostatic properties control
      ion selectivity. This finding highlights the importance of the classical concept
      of field strength. Selectivity for K+ is seen to emerge as a robust feature of a
      flexible fluctuating pore lined by carbonyl groups.

PMID- 15483609
TI  - Low marine sulphate and protracted oxygenation of the Proterozoic biosphere.
AB  - Progressive oxygenation of the Earth's early biosphere is thought to have
      resulted in increased sulphide oxidation during continental weathering, leading
      to a corresponding increase in marine sulphate concentration. Accurate
      reconstruction of marine sulphate reservoir size is therefore important for
      interpreting the oxygenation history of early Earth environments. Few data,
      however, specifically constrain how sulphate concentrations may have changed
      during the Proterozoic era (2.5-0.54 Gyr ago). Prior to 2.2 Gyr ago, when oxygen
      began to accumulate in the Earth's atmosphere, sulphate concentrations are
      inferred to have been <1 mM and possibly <200 microM, on the basis of limited
      isotopic variability preserved in sedimentary sulphides and experimental data
      showing suppressed isotopic fractionation at extremely low sulphate
      concentrations. By 0.8 Gyr ago, oxygen and thus sulphate levels may have risen
      significantly. Here we report large stratigraphic variations in the sulphur
      isotope composition of marine carbonate-associated sulphate, and use a rate
      dependent model for sulphur isotope change that allows us to track changes in
      marine sulphate concentrations throughout the Proterozoic. Our calculations
      indicate sulphate levels between 1.5 and 4.5 mM, or 5-15 per cent of modern
      values, for more than 1 Gyr after initial oxygenation of the Earth's biosphere.
      Persistence of low oceanic sulphate demonstrates the protracted nature of Earth's
      oxygenation. It links biospheric evolution to temporal patterns in the
      depositional behaviour of marine iron- and sulphur-bearing minerals, biological
      cycling of redox-sensitive elements and availability of trace metals essential to
      eukaryotic development.

PMID- 15483610
TI  - A new troodontid dinosaur from China with avian-like sleeping posture.
AB  - Discovering evidence of behaviour in fossilized vertebrates is rare. Even rarer
      is evidence of behaviour in non-avialan dinosaurs that directly relates to
      stereotypical behaviour seen in extant birds (avians) and not previously
      predicted in non-avialan dinosaurs. Here we report the discovery of a new
      troodontid taxon from the Early Cretaceous Yixian Formation of western Liaoning,
      China. Numerous other three-dimensionally preserved vertebrate fossils have been
      recovered recently at this locality, including some specimens preserving
      behavioural information. The new troodontid preserves several features that have
      been implicated in avialan origins. Notably, the specimen is preserved in the
      stereotypical sleeping or resting posture found in extant Aves. Evidence of this
      behaviour outside of the crown group Aves further demonstrates that many bird
      features occurred early in dinosaurian evolution.

PMID- 15483611
TI  - Adaptation varies through space and time in a coevolving host-parasitoid
      interaction.
AB  - One of the central challenges of evolutionary biology is to understand how
      coevolution organizes biodiversity over complex geographic landscapes. Most
      species are collections of genetically differentiated populations, and these
      populations have the potential to become adapted to their local environments in
      different ways. The geographic mosaic theory of coevolution incorporates this
      idea by proposing that spatial variation in natural selection and gene flow
      across a landscape can shape local coevolutionary dynamics. These effects may be
      particularly strong when populations differ across productivity gradients, where
      gene flow will often be asymmetric among populations. Conclusive empirical tests
      of this theory have been particularly difficult to perform because they require
      knowledge of patterns of gene flow, historical population relationships and local
      selection pressures. We have tested these predictions empirically using a model
      community of bacteria and bacteriophage (viral parasitoids of bacteria). We show
      that gene flow across a spatially structured landscape alters coevolution of
      parasitoids and their hosts and that the resulting patterns of adaptation can
      fluctuate in both space and time.

PMID- 15483612
TI  - Hedgehog signalling controls eye degeneration in blind cavefish.
AB  - Hedgehog (Hh) proteins are responsible for critical signalling events during
      development but their evolutionary roles remain to be determined. Here we show
      that hh gene expression at the embryonic midline controls eye degeneration in
      blind cavefish. We use the teleost Astyanax mexicanus, a single species with an
      eyed surface-dwelling form (surface fish) and many blind cave forms (cavefish),
      to study the evolution of eye degeneration. Small eye primordia are formed during
      cavefish embryogenesis, which later arrest in development, degenerate and sink
      into the orbits. Eye degeneration is caused by apoptosis of the embryonic lens,
      and transplanting a surface fish embryonic lens into a cavefish optic cup can
      restore a complete eye. Here we show that sonic hedgehog (shh) and tiggy-winkle
      hedgehog (twhh) gene expression is expanded along the anterior embryonic midline
      in several different cavefish populations. The expansion of hh signalling results
      in hyperactivation of downstream genes, lens apoptosis and arrested eye growth
      and development. These features can be mimicked in surface fish by twhh and/or
      shh overexpression, supporting the role of hh signalling in the evolution of
      cavefish eye regression.

PMID- 15483613
TI  - A relative signalling model for the formation of a topographic neural map.
AB  - The highly ordered wiring of retinal ganglion cell (RGC) neurons in the eye to
      their synaptic targets in the superior colliculus of the midbrain has long served
      as the dominant experimental system for the analysis of topographic neural maps.
      Here we describe a quantitative model for the development of one arm of this map-
      the wiring of the nasal-temporal axis of the retina to the caudal-rostral axis of
      the superior colliculus. The model is based on RGC-RGC competition that is
      governed by comparisons of EphA receptor signalling intensity, which are made
      using ratios of, rather than absolute differences in, EphA signalling between
      RGCs. Molecular genetic experiments, exploiting a combinatorial series of EphA
      receptor knock-in and knockout mice, confirm the salient predictions of the
      model, and show that it both describes and predicts topographic mapping.

PMID- 15483614
TI  - A general mechanism for perceptual decision-making in the human brain.
AB  - Findings from single-cell recording studies suggest that a comparison of the
      outputs of different pools of selectively tuned lower-level sensory neurons may
      be a general mechanism by which higher-level brain regions compute perceptual
      decisions. For example, when monkeys must decide whether a noisy field of dots is
      moving upward or downward, a decision can be formed by computing the difference
      in responses between lower-level neurons sensitive to upward motion and those
      sensitive to downward motion. Here we use functional magnetic resonance imaging
      and a categorization task in which subjects decide whether an image presented is
      a face or a house to test whether a similar mechanism is also at work for more
      complex decisions in the human brain and, if so, where in the brain this
      computation might be performed. Activity within the left dorsolateral prefrontal
      cortex is greater during easy decisions than during difficult decisions, covaries
      with the difference signal between face- and house-selective regions in the
      ventral temporal cortex, and predicts behavioural performance in the
      categorization task. These findings show that even for complex object categories,
      the comparison of the outputs of different pools of selectively tuned neurons
      could be a general mechanism by which the human brain computes perceptual
      decisions.

PMID- 15483615
TI  - Coupled oscillators control morning and evening locomotor behaviour of
      Drosophila.
AB  - Daily rhythms of physiology and behaviour are precisely timed by an endogenous
      circadian clock. These include separate bouts of morning and evening activity,
      characteristic of Drosophila melanogaster and many other taxa, including mammals.
      Whereas multiple oscillators have long been proposed to orchestrate such complex
      behavioural programmes, their nature and interplay have remained elusive. By
      using cell-specific ablation, we show that the timing of morning and evening
      activity in Drosophila derives from two distinct groups of circadian neurons:
      morning activity from the ventral lateral neurons that express the neuropeptide
      PDF, and evening activity from another group of cells, including the dorsal
      lateral neurons. Although the two oscillators can function autonomously, cell
      specific rescue experiments with circadian clock mutants indicate that they are
      functionally coupled.

PMID- 15483616
TI  - Morning and evening peaks of activity rely on different clock neurons of the
      Drosophila brain.
AB  - In Drosophila, a 'clock' situated in the brain controls circadian rhythms of
      locomotor activity. This clock relies on several groups of neurons that express
      the Period (PER) protein, including the ventral lateral neurons (LN(v)s), which
      express the Pigment-dispersing factor (PDF) neuropeptide, and the PDF-negative
      dorsal lateral neurons (LN(d)s). In normal cycles of day and night, adult flies
      exhibit morning and evening peaks of activity; however, the contribution of the
      different clock neurons to the rest-activity pattern remains unknown. Here, we
      have used targeted expression of PER to restore the clock function of specific
      subsets of lateral neurons in arrhythmic per(0) mutant flies. We show that PER
      expression restricted to the LN(v)s only restores the morning activity, whereas
      expression of PER in both the LN(v)s and LN(d)s also restores the evening
      activity. This provides the first neuronal bases for 'morning' and 'evening'
      oscillators in the Drosophila brain. Furthermore, we show that the LN(v)s alone
      can generate 24 h activity rhythms in constant darkness, indicating that the
      morning oscillator is sufficient to drive the circadian system.

PMID- 15483619
TI  - Key words.

PMID- 15483620
TI  - Analyse this.

PMID- 15483622
TI  - Bricks and mortar. Rensselaer Polytechnic Institute.

PMID- 15483624
TI  - Latrophilin fragments behave as independent proteins that associate and signal on
      binding of LTX(N4C).
AB  - Heptahelical, or G-protein-coupled, receptors control many cellular functions and
      normally consist of one polypeptide chain. In contrast, heptahelical receptors
      that belong to the long N-terminus, group B (LNB) family are cleaved
      constitutively into two fragments. The N-terminal fragments (NTFs) resemble cell
      adhesion proteins and the C-terminal fragments (CTFs) are typical G-protein
      coupled receptors (GPCRs) with seven transmembrane regions. However, the
      functional roles of this cleavage and of any subsequent NTF-CTF interactions
      remain to be identified. Using latrophilin, a well-studied member of the LNB
      family, we now demonstrate that cleavage is critical for delivery of this
      receptor to the cell surface. On the plasma membrane, NTF and CTF behave as
      separate membrane proteins involved, respectively, in cell-surface reception and
      signalling. The two fragments can also internalise independently. However,
      separated NTF and CTF can re-associate on solubilisation. Agonist binding to NTF
      on the cell surface also induces re-association of fragments and provokes signal
      transduction via CTF. These findings define a novel principle of structural and
      functional organisation of the cleaved, two-subunit GPCRs.

PMID- 15483625
TI  - Regulation of Bin1 SH3 domain binding by phosphoinositides.
AB  - Bin1/M-amphiphysin-II is an amphiphysin-II isoform highly expressed in transverse
      tubules of adult striated muscle and is implicated in their biogenesis. Bin1
      contains a basic unique amino-acid sequence, Exon10, which interacts with certain
      phosphoinositides such as phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)), to
      localize to membranes. Here we found that Exon10 also binds to the src homology 3
      (SH3) domain of Bin1 itself, and hence blocks the binding of the SH3 domain to
      its canonical PxxP ligands, including dynamin. This blockage was released by
      addition of PI(4,5)P(2) in vitro or in cells overexpressing phosphatidylinositol
      4-phosphate 5-kinase. The Exon10-binding interface of the Bin1 SH3 domain largely
      overlapped with its PxxP-binding interface. We also show that the PLCdelta
      pleckstrin homology domain, another PI(4,5)P(2)-binding module, cannot substitute
      for Exon10 in Bin1 function in transverse tubule formation, and suggest the
      importance of the dual biochemical properties of Exon10 in myogenesis. Our
      results exemplify a novel mechanism of SH3 domain regulation, and suggest that
      the SH3-mediated protein-protein interactions of Bin1 are regulated by Exon10 so
      that it may only occur when Bin1 localizes to certain submembrane areas.

PMID- 15483626
TI  - IRAG is essential for relaxation of receptor-triggered smooth muscle contraction
      by cGMP kinase.
AB  - Signalling by cGMP-dependent protein kinase type I (cGKI) relaxes various smooth
      muscles modulating thereby vascular tone and gastrointestinal motility. cGKI
      dependent relaxation is possibly mediated by phosphorylation of the inositol
      1,4,5-trisphosphate receptor I (IP(3)RI)-associated protein (IRAG), which
      decreases hormone-induced IP(3)-dependent Ca(2+) release. We show now that the
      targeted deletion of exon 12 of IRAG coding for the N-terminus of the coiled-coil
      domain disrupted in vivo the IRAG-IP(3)RI interaction and resulted in hypomorphic
      IRAG(Delta12/Delta12) mice. These mice had a dilated gastrointestinal tract and a
      disturbed gastrointestinal motility. Carbachol- and phenylephrine-contracted
      smooth muscle strips from colon and aorta, respectively, of IRAG(Delta12/Delta12)
      mice were not relaxed by cGMP, while cAMP-mediated relaxation was unperturbed.
      Norepinephrine-induced increases in [Ca(2+)](i) were not decreased by cGMP in
      aortic smooth muscle cells from IRAG(Delta12/Delta12) mice. In contrast, cGMP
      induced relaxation of potassium-induced smooth muscle contraction was not
      abolished in IRAG(Delta12/Delta12) mice. We conclude that cGMP-dependent
      relaxation of hormone receptor-triggered smooth muscle contraction essentially
      depends on the interaction of cGKI-IRAG with IP(3)RI.

PMID- 15483627
TI  - Regulation of nicotinic receptor expression by the ubiquitin-proteasome system.
AB  - Control of ligand-gated ion channel (LGIC) expression is essential for the
      formation, maintenance and plasticity of synapses. Treatment of mouse myotubes
      with proteasome inhibitors increased the number of surface nicotinic
      acetylcholine receptors (AChRs), indicating LGIC expression is regulated by the
      ubiquitin-proteasome system (UPS). Elevated surface expression resulted from
      increased AChR delivery to the plasma membrane and not from decreased turnover
      from the surface. The rise in AChR trafficking was the direct result of increased
      assembly of subunits in the endoplasmic reticulum (ER). Because proteasome
      inhibitors also blocked ER-associated degradation (ERAD) of unassembled AChR
      subunits, the data indicate that the additional AChRs were assembled from
      subunits normally targeted for ERAD. Our data show that AChR surface expression
      is regulated by the UPS through ERAD, whose activity determines oligomeric
      receptor assembly efficiency.

PMID- 15483628
TI  - HSF4 is required for normal cell growth and differentiation during mouse lens
      development.
AB  - The heat shock transcription factor (HSF) family consists of three members in
      mammals and regulates expression of heat shock genes via a heat shock element.
      HSF1 and HSF2 are required for some developmental processes, but it is unclear
      how they regulate these processes. To elucidate the mechanisms of developmental
      regulation by HSFs, we generated mice in which the HSF4 gene is mutated. HSF4
      null mice had cataract with abnormal lens fiber cells containing inclusion-like
      structures, probably due to decreased expression of gamma-crystallin, which
      maintains protein stability. Furthermore, we found increased proliferation and
      premature differentiation of the mutant lens epithelial cells, which is
      associated with increased expression of growth factors, FGF-1, FGF-4, and FGF-7.
      Unexpectedly, HSF1 competed with HSF4 for the expression of FGFs not only in the
      lens but also in other tissues. These findings reveal the lens-specific role of
      HSF4, which activates gamma-crystallin genes, and also indicate that HSF1 and
      HSF4 are involved in regulating expression of growth factor genes, which are
      essential for cell growth and differentiation.

PMID- 15483630
TI  - School food policy at primary and secondary schools in Belgium-Flanders: does it
      influence young people's food habits?
AB  - OBJECTIVE: To describe the availability of food items at primary and secondary
      schools in Belgium-Flanders and to examine the influence of school food policy
      (availability of food items, school food rules, nutrition education programmes)
      and aggregated school socioeconomical status (AGG SES) on the consumption of
      fruit, soft drinks, crisps and sweets, using multilevel modelling. DESIGN,
      SETTING AND SUBJECTS: In spring 2002, 360 schools were invited to participate in
      the Health Behaviour in School-aged Children survey. In January 2003, the same
      schools were asked to complete a short school policy questionnaire. Pupils of 197
      schools participated in the pupil survey (n=16560); 247 school principals
      completed the school questionnaire; for 157 schools data were available for both
      (n=12 360). RESULTS: Mineral water, fruit juice, chocolate milk, and soup were
      available in most schools. Whole fat milk was available in most primary schools;
      soft drinks, diet soft drinks and biscuits were available in most secondary
      schools. Fruit was available in 14% of primary and 26% of secondary schools.
      Assessment of the variation in the outcome variables revealed no significant
      between-school variation in primary schools, but considerable variation between
      secondary schools in the consumption of soft drinks, sweets and crisps (but not
      fruit). School characteristics explaining some of this school variance
      independent of pupil level characteristics were: for soft drinks: availability at
      the school, rules regarding the consumption of sweets and AGG SES; for sweets:
      AGG SES; and for crisps: rules regarding the consumption of savoury snacks and
      AGG SES. CONCLUSION: The results indicate that school food policy can have an
      impact on adolescents' food habits.

PMID- 15483629
TI  - Epigenetic silencing of the c-fms locus during B-lymphopoiesis occurs in discrete
      steps and is reversible.
AB  - The murine c-fms (Csf1r) gene encodes the macrophage colony-stimulating factor
      receptor, which is essential for macrophage development. It is expressed at a low
      level in haematopoietic stem cells and is switched off in all non-macrophage cell
      types. To examine the role of chromatin structure in this process we studied
      epigenetic silencing of c-fms during B-lymphopoiesis. c-fms chromatin in stem
      cells and multipotent progenitors is in the active conformation and bound by
      transcription factors. A similar result was obtained with specified common
      myeloid and lymphoid progenitor cells. In developing B cells, c-fms chromatin is
      silenced in distinct steps, whereby first the binding of transcription factors
      and RNA expression is lost, followed by a loss of nuclease accessibility.
      Interestingly, regions of de novo DNA methylation in B cells overlap with an
      intronic antisense transcription unit that is differently regulated during
      lymphopoiesis. However, even at mature B cell stages, c-fms chromatin is still in
      a poised conformation and c-fms expression can be re-activated by conditional
      deletion of the transcription factor Pax5.

PMID- 15483631
TI  - Nutritional status, well-being and functional ability in frail elderly service
      flat residents.
AB  - OBJECTIVE: To investigate nutritional status and its relationship to cognition,
      well-being, functional ability and energy intake in frail elderly service flat
      residents. DESIGN: Cross-sectional and prospective study. SETTING: Two municipal
      service flat complexes. SUBJECTS: A total of 80 residents (median age 85.5 (79
      90) y) with regular home care assistance participated. A subgroup of 35 residents
      took part in a re-examination 1 y later. METHODS: Mini Nutritional Assessment
      (MNA), Short Portable Mental Status Questionnaire, Barthel Index and Health Index
      were used for the evaluation of nutritional, cognitive and ADL function and well
      being, respectively. RESULTS: In all, 30% of the frail and chronically ill
      service flat residents were assessed as malnourished and 59% were at risk of
      malnutrition. The malnourished residents had worse cognitive conditions (P<0.001)
      and well-being (P<0.05), lower functional ability (P<0.01) and they had a greater
      need for daily assistance (P<0.05) than the other residents. The median night
      fast period was 14.0 (12.5-15.0) h. Five subjects classified as malnourished at
      baseline had lost a median of -9.6 kg (range -11.0 to +7.3 kg) (P<0.05) in body
      weight at the 1-y follow-up, which contrasted significantly from the weight
      stability in residents classified as at risk for malnutrition or well-nourished.
      CONCLUSION: Out of 10 residents, nine were assessed to have impending nutritional
      problems that related to impaired well-being, cognition, and functional ability.
      Malnourished residents had a significant weight loss over one year. Studies are
      needed to determine whether weight loss and nutrition-related dysfunction in
      service flat residents are preventable or treatable.

PMID- 15483632
TI  - Folate intake estimated with an updated database and its association to blood
      folate and homocysteine in Korean college students.
AB  - OBJECTIVE: To measure folate content in cooked foods commonly consumed in Korea
      for evaluating its relation to folate nutriture of college students. DESIGN:
      Folate content in 32 raw and cooked foods was measured by microbiological assay
      after trienzyme extraction. These values and the previously published values of
      110 raw foods commonly consumed in Korea were used to update the currently
      available food tables to estimate dietary folate intake of 106 students based on
      a 3-day 24-h recall. The association of folate intake with blood folate and
      homocysteine concentrations was evaluated. SETTING: Cheongju, Korea. SUBJECTS:
      Healthy college students aged 18 to 27 y old (44 males and 62 females). RESULTS:
      The average folate loss in 32 foods caused by cooking was 29%. The mean daily
      dietary folate intakes estimated with an updated database were 406 and 305 mug in
      males and females, respectively. About 10% of both male and female students
      showed low serum folate (<6.8 nmol/l). Folate intake was positively correlated
      with serum and erythrocyte folate concentrations in female students (r=0.27 and
      0.29, respectively, P<0.05), and negatively correlated with serum homocysteine in
      male students (r=-0.41, P<0.05). CONCLUSIONS: Mean dietary folate intake was
      higher than those of previous studies since the database was updated using values
      obtained with trienzyme extraction. Folate intake for the general population
      should be re-evaluated using reliable food folate values obtained with trienzyme
      extraction.

PMID- 15483633
TI  - Validity of reported energy expenditure and reported intake of energy, protein,
      sodium and potassium in rheumatoid arthritis patients in a dietary intervention
      study.
AB  - OBJECTIVES: The aim of the study was to validate a diet history interview (DHI)
      method and a 3-day activity registration (AR) with biological markers. SUBJECTS
      AND STUDY DESIGN: The reported dietary intake of 33 rheumatoid arthritis patients
      (17 patients on a Mediterranean-type diet and 16 patients on a control diet)
      participating in a dietary intervention study was assessed using the DHI method.
      The total energy expenditure (TEE), estimated by a 3-day AR, was used to validate
      the energy intake (EI). For nine subjects the activity registration was also
      validated by means of the doubly labelled water (DLW) method. The excretion of
      nitrogen, sodium and potassium in 24-h urine samples was used to validate the
      intake of protein, sodium and potassium. RESULTS: There was no significant
      difference between the EI and the TEE estimated by the activity registration or
      between the intake of protein, sodium and potassium and their respective
      biological markers. However, in general, the AR underestimated the TEE compared
      to the DLW method. No significant differences were found between the subjects in
      the Mediterranean diet group and the control diet group regarding the
      relationship between the reported intakes and the biological markers. CONCLUSION:
      The DHI could capture the dietary intake fairly well, and the dietary assessment
      was not biased by the dietary intervention. The AR showed a bias towards
      underestimation when compared to the DLW method. This illustrates the importance
      of valid biological markers.

PMID- 15483634
TI  - Participatory nutrition education and adoption of new feeding practices are
      associated with improved adequacy of complementary diets among rural Malawian
      children: a pilot study.
AB  - OBJECTIVE: To introduce practices for improving complementary feeding and
      evaluate their adoption and association with improved dietary intakes. DESIGN: A
      quasiexperimental pilot study comparing dietary intakes from complementary foods
      among three intervention communities and one control community before and after
      the intervention, and adoption of new complementary feeding practices among
      intervention communities following the intervention. SETTING: Rural subsistence
      communities in southern Malawi, Central Africa. SUBJECTS: Mothers and their
      children aged 6 to 23 months receiving complementary foods. INTERVENTIONS: A
      participatory, nutrition education intervention based on four locally adapted
      lessons for complementary feeding practices designed to increase: (i) total
      complementary food intake; (ii) energy and nutrient density of the complementary
      diet, and; (iii) iron and zinc bioavailability of the complementary diet.
      RESULTS: Adoption rates for the four practices ranged from 25% for preparation of
      enriched porridges, to 10% for preparing soaked, pounded maize. The amount of
      complementary foods (g/day) and intakes of energy, animal protein, niacin,
      riboflavin, calcium, iron, and zinc, but not vitamin A, were significantly
      greater (P<0.05) in the intervention compared to control group, as were the
      energy, iron, and riboflavin density, and the estimated amount of bioavailable
      iron and zinc. CONCLUSIONS: Several intervention practices were well accepted and
      adopted and were associated with improved adequacy of energy and nutrient intakes
      from the complementary diet. Such improvements were attributed mainly to greater
      total intakes and, to a lesser extent, enhanced dietary quality of the
      complementary foods.

PMID- 15483635
TI  - Validation of a food-frequency questionnaire assessment of carotenoid and vitamin
      E intake using weighed food records and plasma biomarkers: the method of triads
      model.
AB  - BACKGROUND: Reliability or validity studies are important for the evaluation of
      measurement error in dietary assessment methods. An approach to validation known
      as the method of triads uses triangulation techniques to calculate the validity
      coefficient of a food-frequency questionnaire (FFQ). OBJECTIVE: To assess the
      validity of an FFQ estimates of carotenoid and vitamin E intake against serum
      biomarker measurements and weighed food records (WFRs), by applying the method of
      triads. DESIGN: The study population was a sub-sample of adult participants in a
      randomised controlled trial of beta-carotene and sunscreen in the prevention of
      skin cancer. Dietary intake was assessed by a self-administered FFQ and a WFR.
      Nonfasting blood samples were collected and plasma analysed for five carotenoids
      (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene) and vitamin
      E. Correlation coefficients were calculated between each of the dietary methods
      and the validity coefficient was calculated using the method of triads. The 95%
      confidence intervals for the validity coefficients were estimated using bootstrap
      sampling. RESULTS: The validity coefficients of the FFQ were highest for alpha
      carotene (0.85) and lycopene (0.62), followed by beta-carotene (0.55) and total
      carotenoids (0.55), while the lowest validity coefficient was for lutein (0.19).
      The method of triads could not be used for beta-cryptoxanthin and vitamin E, as
      one of the three underlying correlations was negative. CONCLUSIONS: Results were
      similar to other studies of validity using biomarkers and the method of triads.
      For many dietary factors, the upper limit of the validity coefficients was less
      than 0.5 and therefore only strong relationships between dietary exposure and
      disease will be detected.

PMID- 15483636
TI  - Serum vitamin B12 concentrations and atrophic gastritis in older New Zealanders.
AB  - OBJECTIVE: To determine the serum vitamin B(12) status of older New Zealanders
      and to assess the impact of atrophic gastritis on vitamin B(12) status. DESIGN: A
      cross-sectional nationally representative population-based survey. METHOD: Serum
      vitamin B(12) concentrations were used to assess vitamin B(12) status. The
      presence and severity of atrophic gastritis was classified using serum pepsinogen
      I and II. SUBJECTS: A total of 466 noninstitutionalized urban and rural dwelling
      New Zealanders aged 65 y or older who participated in the 1997 National Nutrition
      Survey. RESULTS: The prevalence of deficient (<148 pmol/l) and marginal (148-221
      pmol/l) serum vitamin B(12) concentrations was 12 and 28%, respectively. The
      prevalence of atrophic gastritis was 6.7% (severe 3.1%, mild-moderate 3.6%).
      While atrophic gastritis increased the relative risk (RR, 95% CI) of having a
      deficient or marginal serum vitamin B(12) concentration by 21-fold (6-67) and
      five-fold (1-17), respectively, those who had atrophic gastritis made up only 33
      and 6% of the participants with deficient or marginal serum vitamin B(12)
      concentrations. An intake of vitamin B(12) from food that exceeded the
      recommended dietary allowance (2.4 mug/day) did not protect against deficient (RR
      0.5; 95% CI: 0.2, 1.2) or marginal (RR 0.9; 95% CI: 0.5, 1.7) serum vitamin B(12)
      status. Vitamin B(12) supplement users had a reduced risk of having deficient and
      marginal vitamin B(12) status (RR 0.3; 95% CI: 0.1, 0.8). CONCLUSIONS: There is a
      relatively high prevalence of deficient and marginal serum vitamin B(12)
      concentrations among older New Zealanders. However, the prevalence of atrophic
      gastritis was low in the New Zealand elderly compared with other surveys.
      Although atrophic gastritis was a risk factor for low vitamin B(12) status, it
      did not fully explain the prevalence of low serum vitamin B(12).

PMID- 15483638
TI  - Low calcium and vitamin D intake in healthy children and adolescents and their
      correlates.
AB  - BACKGROUND: Optimal dietary calcium and possibly vitamin D intake throughout
      childhood and adolescence may enhance bone mineral accrual. Little data on the
      intake of these nutrients in Mediterranean countries exist, and predictors of
      their suboptimal intake are not well defined. OBJECTIVE: To evaluate
      systematically the effect of gender, lifestyle factors, and socioeconomic status
      on mean calcium and vitamin D intake in healthy school children and adolescents
      from Lebanon. DESIGN: A total of 385 students aged 10-16 y were selected from
      four public and four private schools between Fall 1999 and Spring 2000.
      Information on calcium and vitamin D intake, through a semiquantitative food
      frequency questionnaire that was validated against a 7-day daily record, and on
      socioeconomic and lifestyle factors were obtained. RESULTS: Only 12% of the
      students met the adequate intake (AI) recommendation of 1300 mg of calcium/day,
      and only 16% met the AI recommendation of 200 IU of vitamin D/day. Boys had a
      significantly higher mean daily calcium intake than girls. Socioeconomic status
      as assessed by children's pocket money was a predictor of higher calcium and
      vitamin D intake. Eating breakfast and physical activity were other correlates of
      daily calcium and vitamin D intake. CONCLUSIONS: Only a minority of students in
      our study met the AI for calcium and vitamin D. Gender, lifestyle factors, and
      socioeconomic status were significant predictors of calcium and vitamin D intake.
      Our findings have important implications regarding the institution of dietary
      public health strategies to promote skeletal health in Mediterranean countries
      during a critical time for bone mass accrual.

PMID- 15483637
TI  - Socio-demographic inequalities in the diets of mid-aged Australian women.
AB  - OBJECTIVES: This study reports on the distributions of food and nutrient intakes
      by socio-demographic factors for a large population sample of mid-aged Australian
      women participating in the Australian Longitudinal Study on Women's Health.
      DESIGN: This cross-sectional population-based study used the Cancer Council of
      Victoria food frequency questionnaires to derive estimates of food and nutrient
      intakes. SETTING: Nationwide community-based survey. SUBJECTS: A total of 10561
      women aged 50-55 y, at the time of the survey in 2001. RESULTS: Analysis showed
      favourable patterns of food intake, with frequent consumption of many foods that
      are promoted as components of a healthy diet (eg, fresh fruit, leafy green and
      other vegetables, bread, cereals, milk and meat). Intakes of both foods and
      nutrients varied significantly across socio-demographic groups, with unmarried
      women, and women in 'labouring' occupations (eg, cleaner, factory worker,
      kitchenhand) having poorer nutrient intake. CONCLUSIONS: Although many mid-aged
      women in this sample had generally healthful diets, women in certain socio
      demographic groups (particularly unmarried women and those in labouring
      occupations) had nutrient intakes of concern. As well as helping to address the
      dearth of current data on dietary intakes in the Australian population, the
      results highlight the need for continued targeted public health strategies aimed
      at improving diet of women from the various socio-economic backgrounds.

PMID- 15483639
TI  - Palatability and glucose, insulin and satiety responses of chickpea flour and
      extruded chickpea flour bread eaten as part of a breakfast.
AB  - OBJECTIVE: To determine the effect of adding chickpea flour or extruded chickpea
      flour to white bread on palatability and postprandial glycaemia, insulinaemia and
      satiety. DESIGN: A randomised, single-blind, cross-over study of four 50 g
      available carbohydrate breakfasts. SETTING: School of Exercise and Nutrition
      Sciences, Deakin University. SUBJECTS: In all, 12 healthy subjects were recruited
      through posted notices. Totally, 11 (nine male, two female) completed the study
      (mean+/-s.e.m.; age 32+/-2 y; body mass index, 24.7+/-0.8 kg/m(2)). INTERVENTION:
      After overnight fasting, subjects consumed a control (white) bread (WB) breakfast
      twice, a chickpea bread (CHB) breakfast once and an extruded chickpea bread (EXB)
      breakfast once. Palatability and postprandial blood glucose, insulin and satiety
      responses were determined. Following this, food intakes from an ad libitum buffet
      and for the remainder of the day were assessed. RESULTS: A trend towards a lower
      incremental area under the curve (IAUC) of glucose for the CHB breakfast compared
      to the WB breakfast was observed (P=0.087). The IAUC of insulin and insulinaemic
      index (II) of the CHB breakfast were higher (P<0.05) than for the WB breakfast.
      No differences in glycaemic index (GI), satiety response, food intake or
      palatability were observed. CONCLUSIONS: CHB and EXB demonstrated acceptable
      palatability. CHB demonstrated some hypoglycaemic effect compared to WB, but
      neither CHB nor EXB demonstrated effects on satiety or food intake. The
      hyperinsulinaemic effect of CHB observed in this study requires further
      investigation.

PMID- 15483640
TI  - Screening for FMR-1 premutations in 122 older Flemish males presenting with
      ataxia.
AB  - Recently, Hagerman et al described the occurrence of a late-onset neurological
      disorder in five male carriers of the fragile-X (FMR-1) premutation. The major
      characteristics of this disorder, designated the Fragile-X Tremor Ataxia Syndrome
      (FXTAS), are progressive intention tremor, cerebellar ataxia and cognitive
      decline. Most cases of FXTAS published thus far were ascertained through families
      with a known fragile-X proband. Since cerebellar ataxia is one of the main
      cardinal features, we performed FMR-1 premutation screening in 122 male patients,
      older than 50 years, who were referred to us for testing of the spinocerebellar
      ataxia (SCA 1, 2, 3, 6, 7) genes and who were found to be negative. In this group
      of patients, we found five patients with an FMR-1 premutation. In four of them, a
      definite diagnosis of FXTAS could be made, based on the proposed diagnostic
      clinical and radiological criteria for FXTAS. In light of these figures, we
      recommend that FMR-1 analysis should be included in the molecular diagnostic work
      up in the group of male ataxia patients older than 50 years.

PMID- 15483641
TI  - One third of Danish hypertrophic cardiomyopathy patients with MYH7 mutations have
      mutations [corrected] in MYH7 rod region.
AB  - Familial hypertrophic cardiomyopathy (FHC) is, in most cases, a disease of the
      sarcomere, caused by a mutation in one of 10 known sarcomere disease genes. More
      than 266 mutations have been identified since 1989. The FHC disease gene first
      characterized MYH7, encodes the cardiac beta-myosin heavy chain, and contains
      more than 115 of these mutations. However, in most studies, only the region
      encoding the globular head and the hinge region of the mature cardiac beta-myosin
      heavy chain have been investigated. Furthermore, most studies carries out
      screening for mutations in the most prevalent disease genes, and discontinues
      screening when an apparent disease-associated mutation has been identified. The
      aim of the present study was to screen for mutations in the rod region of the
      MYH7 gene in all probands of the cohort, regardless of the known genetic status
      of the proband. Three disease-causing mutations were identified in the rod region
      in four probands using capillary electrophoresis single-strand conformation
      polymorphism as a screening method. All mutations were novel: N1327K, R1712W, and
      E1753K. Two of the probands had already been shown to carry other FHC-associated
      mutations. In conclusion, we show that in the Danish cohort we find one third of
      all MYH7 mutations in the rod-encoding region and we find that two of the
      patients carrying these mutations also carry mutations in other FHC disease genes
      stressing the need for a complete screening of all known disease genes in FHC
      patients.

PMID- 15483642
TI  - A combination of three common inherited mitochondrial DNA polymorphisms promotes
      longevity in Finnish and Japanese subjects.
AB  - Mitochondrial DNA (mtDNA) coding region polymorphisms, as well as the 150T
      polymorphism in the noncoding region, have been associated with longevity. We
      have studied here the association of 150T with longevity further and assessed
      differences in this association between various mtDNA haplogroups. We analysed a
      sample of 321 very old subjects and 489 middle-aged controls from Finland and
      Japan. 150T was more frequent among the very old than among the controls in both
      the Finnish and Japanese subjects. Interestingly, the association was not similar
      in all haplogroups, and a stratified analysis revealed that two additional common
      polymorphisms, 489C and 10398G, modified the association between 150T and
      longevity. These findings suggest that longevity is partly determined by
      epistatic interactions involving these three mtDNA loci.

PMID- 15483643
TI  - Computer-assisted prenatal aneuploidy screening for chromosome 13, 18, 21, X and
      Y based on multiplex ligation-dependent probe amplification (MLPA).
AB  - In routine prenatal diagnostics we used a commercial multiplex ligation-dependent
      probe amplification (MLPA) kit for aneuploidy screening for chromosomes 13, 18,
      21, X and Y. We present the results of 1593 consecutive prenatal samples analysed
      and diagnosed prior to knowledge of the G-banding analysis during 8-month routine
      use of computer-assisted MLPA aneuploidy screening. In total, 27 aneuploidies
      were detected. There were no false positive results while two false negative
      results could be explained by a placental mosaicism and a partial monosomy,
      respectively. In total, 3.2% of the samples were inconclusive. We conclude that
      automatic computer assisted MLPA is a rapid, simple and reliable method for
      detection of aneuploidies in prenatal diagnostics.

PMID- 15483644
TI  - Complex segregation analysis of nasopharyngeal carcinoma in Guangdong, China:
      evidence for a multifactorial mode of inheritance (complex segregation analysis
      of NPC in China).
AB  - The striking geographical and ethnic distribution of nasopharyngeal carcinoma
      (NPC) suggests the involvement of genetic and environmental factors in NPC
      development. The purpose of this study is to investigate the fit of single gene,
      polygenic and multifactorial models to the observed pattern of transmission of
      NPC in a hospital-based family history study conducted by the Cancer Center of
      Sun Yat-Sen University (CCSYU) in Guangzhou, China. Complex segregation analysis
      of a total of 1903 Cantonese pedigrees ascertained at CCSYU was conducted using a
      unified mixed model after the pedigrees were partitioned into 3737 nuclear
      families. The mixed model assumes that a phenotype is influenced by the additive
      and independent effect of a major gene, together with multifactorial components
      (genetic and environmental) and a random environmental effect. The current
      results do not provide evidence for a major gene and the observed data are best
      explained by a multifactorial mode of inheritance for NPC.

PMID- 15483645
TI  - Duchenne muscular dystrophy: stalled at the junction?

PMID- 15483646
TI  - Delineation of mechanisms and regions of dosage imbalance in complex
      rearrangements of 1p36 leads to a putative gene for regulation of cranial suture
      closure.
AB  - Structural chromosome abnormalities have aided in gene identification for over
      three decades. Delineation of the deletion sizes and rearrangements allows for
      phenotype/genotype correlations and ultimately assists in gene identification. In
      this report, we have delineated the precise rearrangements in four subjects with
      deletions, duplications, and/or triplications of 1p36 and compared the regions of
      imbalance to two cases recently published. Fluorescence in situ hybridization
      (FISH) analysis revealed the size, order, and orientation of the
      duplicated/triplicated segments in each subject. We propose a premeiotic model
      for the formation of these complex rearrangements in the four newly ascertained
      subjects, whereby a deleted chromosome 1 undergoes a combination of multiple
      breakage-fusion-bridge (BFB) cycles and inversions to produce a chromosome arm
      with a complex rearrangement of deleted, duplicated and triplicated segments. In
      addition, comparing the six subjects' rearrangements revealed a region of overlap
      that when triplicated is associated with craniosynostosis and when deleted is
      associated with large, late-closing anterior fontanels. Within this region are
      the MMP23A and -B genes. We show MMP23 gene expression at the cranial sutures and
      we propose that haploinsufficiency results in large, late-closing anterior
      fontanels and overexpression results in craniosynostosis. These data emphasize
      the important role of cytogenetics in investigating and uncovering the etiologies
      of human genetic disease, particularly cytogenetic imbalances that reveal
      potentially dosage-sensitive genes.

PMID- 15483647
TI  - Pedigree linkage disequilibrium mapping of quantitative trait loci.
AB  - In this paper, we propose to use pedigrees of any size and any types of relatives
      in joint high-resolution linkage disequilibrium (LD) and linkage mapping of
      quantitative trait loci (QTL) by variance component models. Two or multiple
      markers can be simultaneously used in modeling association with the trait locus,
      instead of using one marker a time in the analysis. The proposed method can
      provide a unified result by using two or multiple markers in the modeling. This
      may avoid the complications of different results obtained from the separate
      analysis of marker by marker. The models simultaneously incorporate both linkage
      and LD information. The measures of LD are modeled by mean coefficients, and
      linkage information is modeled by variance-covariance matrix. Using analytical
      formulas to calculate the regression coefficients, the genetic effects are shown
      to be decomposed into additive and dominance components. The noncentrality
      parameter approximations of test statistics of LD are provided to make power
      calculations. Power and type I error rates are explored to investigate the merit
      of the proposed method by both the analytical formulas and simulations. Comparing
      with the association between-family and association within-family ('AbAw')
      approach of Fulker and Abecasis et al, it is evident that the method proposed in
      this article is more powerful. The method is applied to investigate the relation
      between polymorphisms in the angiotensin 1-converting enzyme (ACE) genes and
      circulating ACE levels, with a better result than that of the 'AbAw' approach.
      Moreover, two markers I/D and 4656(CT)3/2 can fully interpret association with
      the trait locus at a 0.01 significance level, which provides a unique result for
      the ACE data.

PMID- 15483648
TI  - Loss of lysosomal association of cystatin B proteins representing progressive
      myoclonus epilepsy, EPM1, mutations.
AB  - Loss-of-function mutations in the cystatin B (CSTB), a cysteine protease
      inhibitor, gene underlie progressive myoclonus epilepsy of Unverricht-Lundborg
      type (EPM1), characterized by myoclonic and tonic-clonic seizures, ataxia and a
      progressive course. A minisatellite repeat expansion in the promoter region of
      the CSTB gene is the most common mutation in EPM1 patients and leads to reduced
      mRNA levels. Seven other mutations altering the structure of CSTB, or predicting
      altered splicing, have been described. Using a novel monoclonal CSTB antibody and
      organelle-specific markers in human primary myoblasts, we show here that
      endogenous CSTB localizes not only to the nucleus and cytoplasm but also
      associates with lysosomes. Upon differentiation to myotubes, CSTB becomes
      excluded from the nucleus and lysosomes, suggesting that the subcellular
      distribution of CSTB is dependent on the differentiation status of the cell. Four
      patient mutations altering the CSTB polypeptide were transiently expressed in BHK
      21 cells. The p.Lys73fsX2-truncated mutant protein shows diffuse cytoplasmic and
      nuclear distribution, whereas p.Arg68X is rapidly degraded. Two missense
      mutations, the previously described p.Gly4Arg affecting the highly conserved
      glycine, critical for cathepsin binding, and a novel mutation, p.Gln71Pro, fail
      to associate with lysosomes. These data imply an important lysosome-associated
      physiological function for CSTB and suggest that loss of this association
      contributes to the molecular pathogenesis of EPM1.

PMID- 15483649
TI  - Mutations including the promoter region of myocilin/TIGR gene.
AB  - Mutations in the MYOC/TIGR gene are responsible for autosomal dominant primary
      open angle glaucoma (POAG). Almost all mutations responsible for POAG have been
      detected in the coding region (in particular at exon 3). By using the techniques
      of PCR, SSCP, automated sequencing and restriction analysis, we have studied 79
      patients suffering from glaucoma. We have found five patients with sequence
      variants in the consensus region of the promoter. These sequence variants might
      be involved in the altered association between the consensus region and the
      corresponding transcription factor. This possibility might be favouring the
      association of other transcription factors, which would operate as activators or
      inhibitors of the transcription, altering the MYOC/TIGR expression.

PMID- 15483650
TI  - Evaluation of NSD2 and NSD3 in overgrowth syndromes.
AB  - Sotos syndrome is an overgrowth condition predominantly caused by truncating
      mutations, missense mutations restricted to functional domains, or deletions of
      NSD1. NSD1 is a member of a protein family that includes NSD2 and NSD3, both of
      which show 70-75% sequence identity with NSD1. This strong sequence similarity
      suggests that abrogation of NSD2 or NSD3 function may cause non-NSD1 Sotos cases
      or other overgrowth phenotypes. To evaluate this hypothesis, we mutationally
      screened NSD2 and NSD3 in 78 overgrowth syndrome cases in which NSD1 mutations
      and deletions had been excluded. Additionally, we used microsatellite markers
      within the vicinity of the genes to look for whole gene deletions. No truncating
      mutations or gene deletions were identified in either gene. We identified two
      conservative missense NSD2 alterations in two non-Sotos overgrowth cases but
      neither was within a functional domain. We identified three synonymous and two
      intronic variants in NSD2 and two synonymous base substitutions in NSD3. Our
      results suggest that despite strong sequence similarity between NSD1, NSD2 and
      NSD3, the latter genes are unlikely to be making a substantial contribution to
      overgrowth phenotypes and thus may operate in distinct functional pathways from
      NSD1.

PMID- 15483651
TI  - Genotype-based screening for hereditary haemochromatosis. I: Technical
      performance, costs and clinical relevance of a German pilot study.
AB  - In 2001, we initiated a pilot study on DNA-based screening of hereditary
      haemochromatosis (HH) in Germany. A total of 5882 insurants of the German
      sickness fund Kaufmannische Krankenkasse-KKH requested information on this
      project, and 3961 of these individuals provided blood samples for testing of the
      HFE mutation C282Y. Of these, 3930 samples were successfully tested with two
      independent test methods, and the results were communicated to the referring
      doctors. In all, 67 of the tested individuals were homozygous for C282Y.
      Partially, this high rate (1.7%) can be explained by the fact that 42.6% of the
      homozygotes already knew their clinical diagnosis HH before sending the blood
      sample. Iron accumulation with further signs or symptoms of HH was present in
      eight of 34 newly diagnosed C282Y homozygous individuals. Two major aspects of
      our study were the analytic validity and the direct laboratory costs of different
      test methods. Of 7860 tests performed, 7841 (99.6%) gave correct results. The
      overall error rate was 0.24% (95% CI: 0.15-0.38%). The analytic specificity of
      the tests methods with respect to the detection of homozygosity for C282Y was
      100% (7726 of 7726 nonhomozygous test challenges, 95% CI: 99.95-100%), while the
      analytic sensitivity was 97% (130 of 134 homozygous test challenges, 95% CI: 92.5
      99.2%). The direct costs ranged from 11.20-16.35 ?[euro] per test method. We
      conclude that the test methods for C282Y are robust, highly sensitive and
      specific, and that a DNA-based HH-screening program can be performed at
      reasonable laboratory costs.

PMID- 15483653
TI  - Inheritance of spontaneous mutant homostyles in Turnera subulata x krapovickasii
      and in autotetraploid T. scabra (Turneraceae).
AB  - To explore the genetic architecture of distyly in Turnera spp., we determined the
      inheritance and compatibility behaviour of two spontaneous homostyled mutants. A
      long-homostyled mutant shoot arose on an otherwise short-styled plant that was an
      artificial hybrid (Turnera subulata x T. krapovickasii) between two diploid
      distylous species. The mutation appears to be an allele, SH, of the distyly locus
      with the dominance relationships, S>SH>s, where S confers the short-styled
      phenotype, SH confers homostyly in SHSH and SHs genotypes, and ss genotypes are
      long-styled. Aberrant segregation ratios were observed among some crosses and
      might be the result of pollen competition. Compatibility relationships are
      consistent with the hypothesis that a gene complex determines distyly.
      Infrequently, revertant short-styled flowers have appeared on cuttings of the T.
      subulata x T. krapovickasii mutant and on occasion, short-styled progeny have
      appeared in crosses where none were expected. A second mutant homostyle was
      discovered in autotetraploid T. scabra. The mutation is inherited as above,
      however, tetrasomic inheritance occurs at the locus. This homostyled mutant
      carries two copies of the SH allele and has the duplex genotype SHSHss.
      Compatibility relationships were as observed above. The occurrence of homostyled
      mutants is consistent with the hypothesis that a linked gene complex underlies
      the inheritance of distyly in Turnera but we cannot discount the hypothesis that
      an allelic series is responsible.

PMID- 15483652
TI  - Distinct effects of single amino-acid changes to tuberin on the function of the
      tuberin-hamartin complex.
AB  - Tuberous sclerosis is an autosomal dominant human disorder caused by inactivating
      mutations to either the TSC1 or TSC2 tumour suppressor gene. Hamartin and
      tuberin, the TSC1 and TSC2 gene products, interact and the tuberin-hamartin
      complex inhibits cell growth by antagonising signal transduction to downstream
      effectors of the mammalian target of rapamycin (mTOR) through the small GTPase
      rheb. Previously, we showed that pathogenic tuberin amino-acid substitutions
      disrupt the tuberin-hamartin complex. Here, we investigate how these mutations
      affect the role of tuberin in the control of signal transduction through mTOR.
      Our data indicate that specific amino-acid substitutions have distinct effects on
      tuberin function.

PMID- 15483654
TI  - QTL for body weight and condition factor in Atlantic salmon (Salmo salar):
      comparative analysis with rainbow trout (Oncorhynchus mykiss) and Arctic charr
      (Salvelinus alpinus).
AB  - Genotypes at 91 microsatellite loci in three full-sib families were used to
      search for QTL affecting body weight (BW) and condition factor in North American
      Atlantic salmon (Salmo salar). More than one informative marker was identified on
      16-18 linkage groups in each family, allowing at least one chromosomal interval
      to be analyzed per linkage group. Two significant QTL for BW on linkage groups AS
      8 and AS-11, and four significant QTL for condition factor on linkage groups AS
      2, AS-5, AS-11, and AS-14 were identified. QTL for both BW and condition factor
      were located on linkage groups AS-1, 6, 8, 11, and 14 when considering both
      significant and suggestive QTL effects. The largest QTL effects for BW (AS-8) and
      for condition factor (AS-14) accounted for 20.1 and 24.9% of the trait variation,
      respectively. Three of the QTL for BW occur on linkage groups where similar
      effects have been detected on the homologous regions in either rainbow trout
      (Oncorhynchus mykiss) or Arctic charr (Salvelinus alpinus).

PMID- 15483655
TI  - Phylogeography of the threatened crayfish (genus Austropotamobius) in Italy:
      implications for its taxonomy and conservation.
AB  - A nucleotide sequence analysis of a portion of the mitochondrial large ribosomal
      subunit was performed to define the phylogeography of the threatened crayfish
      Austropotamobius (Decapoda; Astacidae) in Italy. We collected 61 specimens from
      31 localities across the Italian peninsula. For the phylogenetic inference, we
      combined the 61 Austropotamobius spp sequences obtained from this study with 18
      sequences deposited in GenBank and corresponding to Italian, French, Irish,
      Swiss, and Slovenian locations. Among the analysed sequences, 34 distinct
      haplotypes were detected. Our results confirmed the presence of both A. pallipes
      and A. italicus in the Italian peninsula and the existence within the latter
      species of a strong intraspecific genetic variation, due to the occurrence of
      four subspecies with a well-defined geographic distribution. From a conservation
      viewpoint, Italy, with its high haplotype variability, may be considered a 'hot
      spot' for the genetic diversity of the European native crayfish Austropotamobius.
      We suggest that re-introduction programs should be conducted with extreme caution
      in Italy, since not only the two Austropotamobius species but also the four A.
      italicus subspecies are genetically and taxonomically separate units and require
      independent conservation plans.

PMID- 15483656
TI  - Adaptive basis of codon usage in the haploid moss Physcomitrella patens.
AB  - Patterns of codon usage bias were studied in the moss model species
      Physcomitrella patens. A total of 92 nuclear, protein coding genes were employed,
      and estimated levels of gene expression were tested for association with two
      measures of codon usage bias and other variables hypothesized to be associated
      with gene expression. Codon bias was found to be positively associated both with
      estimated levels of gene expression and GC content in the coding parts of studied
      genes. However, GC content in noncoding parts, that is, introns and 5' and 3'
      untranslated regions (UTRs), was not associated with estimated levels of gene
      expression. It is argued that codon bias is not shaped by mutational bias, but
      rather by weak natural selection for translational efficiency in P. patens. The
      possible role of life history characteristics in shaping patterns of codon usage
      in this species is discussed.

PMID- 15483657
TI  - Mitochondrial COI-NC-COII sequences in talitrid amphipods (Crustacea).
AB  - Mitochondrial (mt) sequences from cytochrome oxidase subunit I to the subunit II
      gene (COI, COII) were analysed in crustacean talitrid amphipods. Species of the
      genera Orchestia, Talitrus and Talorchestia from the Mediterranean-East Atlantic
      area were examined. The expected tRNALeu-UUR gene was not revealed between COI
      and COII. Instead, a short (35-48 bp) noncoding (NC) AT-rich (ca. 90%) region
      with putative stem loops was found. Here, we discuss briefly the NC region and
      explore its potential involvement in generating this novel rearrangement. The COI
      NC-COII organization, as well as preliminary phylogenetic results, based on both
      COI-COII nucleotide and amino-acid sequence indicate monophyly of these talitrid
      taxa.

PMID- 15483658
TI  - Importance of patient selection when determining the significance of the CYP3A5
      polymorphism in clinical trials.

PMID- 15483659
TI  - Availability of pharmacogenomics-based prescribing information in drug package
      inserts for currently approved drugs.

PMID- 15483660
TI  - Evolution of the mannose-binding lectin gene in primates.
AB  - The mannose-binding lectin MBL2 plays an important role in the innate immune
      system. It binds carbohydrates surface, acts as an opsonin and activates the
      complement system. With the aim of studying the evolution of the MBL2 gene in
      primates, we sequenced its coding region in 12 non-human primate species and
      compared them with the human sequence. We demonstrated that nucleotide and amino
      acidic sequences of the MBL2 among primates are highly homologous, underlining
      the importance of this molecule in the defense system against pathogen invasions.
      In particular, in the collagen-like domain that confers the characteristic
      structure to MBL2 protein, the identity among primates is really high. In the
      carbohydrate recognition domain, we evidenced some primates' group-specific amino
      acidic mutations not resulting in changes of the structure or function of this
      MBL2 domain. Phylogenetic analysis did not evidence any positive selective
      pressure in MBL2 gene among non-human primates. Our findings indicate that MBL2
      is well conserved in agreement with its important role in the immune system: in
      non-human primates, we did not observe the same 'plasticity' of the MBL2 human
      gene, where a frequency of more than 1% of nucleotide variations was described in
      the coding and promoter regions.

PMID- 15483661
TI  - The EIF2AK3 gene region and type I diabetes in subjects from South India.
AB  - Mutations in the EIF2AK3 gene underlie susceptibility to the Wolcott-Rallison
      syndrome, which is a monogenic disease associated with insulin-deficient neonatal
      diabetes. Furthermore, suggestive evidence of linkage between type 1 diabetes
      (T1DM) and the EIF2KA3 chromosomal region has been reported in Scandinavian
      families. We have investigated the hypothesis that polymorphic variants in and
      around the EIF2AK3 gene might partially account for susceptibility to T1DM in
      South Indian subjects. Excess transmission of the common alleles of two
      polymorphic markers (D2S1786 and 15INDEL, located within the gene) downstream of
      EIF2AK3, either singly (D2S1786, P = 0.01) and 15INDEL (P = 0.02) or as a
      combination (P < 0.001), were found in 234 families with a T1DM proband. There
      was also a clear paternal effect for the 15INDEL marker (P = 0.005) on disease
      susceptibility. The presence of the common allele of both markers was found in
      decreased frequency in the subjects with normal glucose tolerance compared to
      probands with T1DM (both P <or= 0.0001). Major common mutations of the EIF2AK3
      gene in T1DM were excluded. In conclusion, this pilot study demonstrates an
      association between the region around the EIF2AK3 locus and T1DM susceptibility.

PMID- 15483662
TI  - Definition of polymorphisms and haplotypes in the interleukin-12B gene:
      association with IL-12 production but not with Crohn's disease.
AB  - Interleukin-12 (IL-12) is a key cytokine for the induction of Th1 immune
      responses. Recently, functional polymorphisms in IL-12p40 (IL12B) were found to
      be associated with susceptibility to several autoimmune diseases. Similarly,
      variation in IL12B might be involved in susceptibility to Crohn's disease (CD), a
      chronic inflammatory bowel disorder associated with high IL-12 expression. We
      searched for additional polymorphism in IL12B and genotyped a large cohort of CD
      patients. Differential in vitro secretors of IL-12 were tested for polymorphism.
      Polymorphisms were analyzed using the intrafamilial transmission disequilibrium
      test (TDT) and by case-control analysis. A novel polymorphism was strongly
      associated with differential expression of IL-12. However, no association with
      susceptibility to CD was seen for this and other polymorphisms. The high level of
      conservation is consistent with the key regulatory role of IL-12. The lack of
      association with IL12B makes it unlikely that this gene is directly involved in
      the susceptibility to CD.

PMID- 15483663
TI  - Context-dependency of the relation between left ventricular mass and AGT gene
      variants.
AB  - In the European Project on Genes in Hypertension (EPOGH), we investigated in
      three populations to what extent in a family-based study, left ventricular mass
      (LVM) was associated with the C-532T and G-6A polymorphisms in the
      angiotensinogen (AGT) gene. We randomly recruited 221 nuclear families (384
      parents and 440 offspring) in Cracow (Poland), Novosibirsk (Russia), and Mirano
      (Italy). Echocardiographic LVM was indexed to body surface area, adjusted for
      covariables, and subjected to multivariate analyses, using generalized estimating
      equations and quantitative transmission disequilibrium tests in a population
      based and family-based approach, respectively. We found significant differences
      between the two Slavic centres and Mirano in left ventricular mass index (LVMI)
      (94.9 vs 80.4 g/m2), sodium excretion (229 vs 186 mmol/day), and the prevalence
      of the AGT -6A (55.7 vs 40.6%) and -532T (16.8 vs 9.4%) alleles. In population
      based as well as in family-based analyses, we observed positive associations of
      LVMI and mean wall thickness (MWT) with the -532T allele in Slavic, but not in
      Italian male offspring. Furthermore, in Slavic male offspring, LVMI and MWT were
      significantly higher in carriers of the -532T/-6A haplotype than in those with
      the -532C/-6G or -532C/-6A allele combinations. In women, LVMI was neither
      associated with single AGT gene variants nor with the haplotypes (0.19 < P
      <0.98). In Slavic offspring carrying the AGT -532C/-6G or -532C/-6A haplotypes,
      LVMI significantly increased with higher sodium excretion (+3.5 g/m2/100 mmol;
      P=0.003), whereas such association was not present in -532T/-6A haplotype
      carriers (P-value for interaction 0.04). We found a positive association between
      LVMI and the AGT -532T allele due to increased MWT. This relation was observed in
      Slavic male offspring. It was therefore dependent on gender, age and ecogenetic
      context, and in addition it appeared to be modulated by the trophic effects of
      salt intake on LVM.

PMID- 15483665
TI  - Efficient and stable Sendai virus-mediated gene transfer into primate embryonic
      stem cells with pluripotency preserved.
AB  - Efficient gene transfer and regulated transgene expression in primate embryonic
      stem (ES) cells are highly desirable for future applications of the cells. In the
      present study, we have examined using the nonintegrating Sendai virus (SeV)
      vector to introduce the green fluorescent protein (GFP) gene into non-human
      primate cynomolgus ES cells. The GFP gene was vigorously and stably expressed in
      the cynomolgus ES cells for a year. The cells were able to form fluorescent
      teratomas when transplanted into immunodeficient mice. They were also able to
      differentiate into fluorescent embryoid bodies, neurons, and mature blood cells.
      In addition, the GFP expression levels were reduced dose-dependently by the
      addition of an anti-RNA virus drug, ribavirin, to the culture. Thus, SeV vector
      will be a useful tool for efficient gene transfer into primate ES cells and the
      method of using antiviral drugs should allow further investigation for regulated
      SeV-mediated gene expression.

PMID- 15483666
TI  - The Ad5 fiber mediates nonviral gene transfer in the absence of the whole virus,
      utilizing a novel cell entry pathway.
AB  - The interesting discovery reported here that soluble adenovirus serotype 5 (Ad5)
      fiber proteins enter cells without the virus was a serendipitous result during
      our development of Ad5 capsid proteins as nonviral gene transfer vectors. The Ad5
      capsid fiber and penton proteins mediate infection. The fiber docks to a
      noninternalizing cell surface protein called the coxsackievirus-Ad receptor
      (CAR), followed by penton binding to integrins, triggering integrin-mediated
      endocytosis of the virus. In our previous work, we assembled the nonviral
      complex, 3PO, which utilized the penton to mediate gene transfer through integrin
      binding and endocytosis. Here, we tested whether incorporating the fiber targets
      3PO to CAR, thus recapitulating the Ad5 infection pathway. As CAR is not an
      endocytic receptor, we were surprised to find that the fiber alone, without the
      penton, enabled gene transfer by binding CAR, but internalizing through an
      unknown mechanism. We show here that the fiber distributes to the nucleus and
      cytoplasm after temperature-independent uptake, whereas the penton accumulates
      around the nucleus after temperature-dependent uptake. Fiber uptake by HeLa cells
      is also actin-dependent, requires the fiber tail/shaft region, and is largely
      inhibited by heparin. This study raises the possibility that alternative pathways
      may enable both viral and nonviral cell entry.

PMID- 15483667
TI  - Direct evidence for the absence of intercellular trafficking of VP22 fused to GFP
      or to the herpes simplex virus thymidine kinase.
AB  - The treatment of solid tumors by retroviral delivery of the herpes simplex virus
      thymidine kinase (TK) followed by ganciclovir (GCV) treatment has so far shown
      only limited success in patients. One major drawback in this approach is the lack
      of efficient in vivo gene delivery to cancer cells. Although, the transduction of
      every single tumor cell is not a requirement since the bystander effect (BE)
      mediated by gap junctions allows the diffusion of the toxic GCV metabolites from
      TK-expressing cells toward untransduced cells. To render the TK/GCV approach more
      potent, and independent of the level of gap junctions, we have tested the
      efficiency of a TK mutant (TK30) fused to VP22, a herpes simplex protein that
      seems to be capable of intercellular trafficking. We failed to detect an increase
      in the BE with cells expressing VP22 fused to TK30 versus cells containing TK30
      alone, and this result forced us to reinvestigate the trafficking properties of
      VP22. Using very sensitive Western blot and fluorescence assays, we were not able
      to detect the spread of VP22 fused either to TK30 or GFP. These results indicate
      that VP22 cannot be used as a cargo to translocate TK30 or GFP.

PMID- 15483668
TI  - Comparison of high-capacity and first-generation adenoviral vector gene delivery
      to murine muscle in utero.
AB  - In utero gene delivery could offer the advantage of treatment at an early stage
      for genetic disorders such as Duchenne muscular dystrophy (DMD) in which the
      inevitable process of muscle degeneration is already initiated at birth.
      Furthermore, treatment of fetal muscle with adenoviral (Ad) vectors is attractive
      because of a high density of Ad receptors, easy vector accessibility due to
      immaturity of the basal lamina and the possibility of treating stem cells.
      Previously, we demonstrated the efficient transduction of fetal muscle by high
      capacity Ad (HC-Ad) vectors. In this study, we compared HC-Ad and first
      generation Ad (FG-Ad) vectors for longevity of lacZ transgene expression,
      toxicity and induction of immunity after direct vector-mediated in utero gene
      delivery to fetal C57BL/6 mice muscle 16 days after conception (E-16). The total
      amount of beta-galactosidase (betagal) expressed from the HC-Ad vector remained
      stable for the 5 months of the study, although the concentration of betagal
      decreased due to muscle growth. Higher survival rates that reflect lower levels
      of toxicity were observed in those mice transduced with an HC-Ad vector as
      compared to an FG-Ad vector. The toxicity induced by FG-Ad vector gene delivery
      was dependent on mouse strain and vector dose. Animals treated with either HC-Ad
      and FG-Ad vectors developed non-neutralizing antibodies against Ad capsid and
      antibodies against betagal, but these antibodies did not cause loss of vector
      genomes from transduced muscle. In a mouse model of DMD, dystrophin gene transfer
      to muscle in utero using an HC-Ad vector restored the dystrophin-associated
      glycoproteins. Our results demonstrate that long-term transgene expression can be
      achieved by HC-Ad vector-mediated gene delivery to fetal muscle, although
      strategies of vector integration may need to be considered to accommodate muscle
      growth.

PMID- 15483669
TI  - Augmentation of the migratory ability of DC-based vaccine into regional lymph
      nodes by efficient CCR7 gene transduction.
AB  - Although dendritic cell (DC)-based immunotherapy is considered a promising
      approach for cancer treatment, a large quantity of DC vaccine is required for
      effective sensitization/activation of immune cells because of the poor migratory
      ability of administered DCs into regional lymphoid tissue. In this study, we
      created a DC vaccine sufficiently transduced with CC chemokine receptor-7 gene
      (CCR7/DCs) by applying RGD fiber-mutant adenovirus vector (AdRGD), and
      investigated its immunological characteristics and therapeutic efficacy. CCR7/DCs
      acquired strong chemotactic activity for CC chemokine ligand-21 (CCL21) and
      exhibited an immunophenotype similar to mature DCs but not immature DCs with
      regard to major histocompatibility complex/costimulatory molecule-expression
      levels and allogenic T cell proliferation-stimulating ability, while maintaining
      inherent endocytotic activity. Importantly, CCR7/DCs injected intradermally into
      mice could accumulate in draining lymph nodes about 5.5-fold more efficiently
      than control AdRGD-applied DCs. Reflecting these properties of CCR7/DCs, DC
      vaccine genetically engineered to simultaneously express endogenous antigen and
      CCR7 could elicit more effective antigen-specific immune response in vivo using a
      lower dosage than DC vaccine transduced with antigen alone. Therefore, the
      application of CCR7/DCs having positive migratory ability to lymphoid tissues may
      contribute to reduction of efforts and costs associated with DC vaccine
      preparation by considerably reducing the DC vaccine dosage needed to achieve
      effective treatment by DC-based immunotherapy.

PMID- 15483670
TI  - An antiaggregation gene therapy strategy for Lewy body disease utilizing beta
      synuclein lentivirus in a transgenic model.
AB  - Current experimental gene therapy approaches for Parkinson's disease (PD) and
      dementia with Lewy bodies (DLB) include the use of viral vectors expressing
      antiapoptosis genes, neurotrophic factors and dopaminergic system enzymes.
      However, since increasing evidence favors a role for alpha-synuclein accumulation
      in the pathogenesis of these disorders, an alternative therapy might require the
      transfer of genes that might block alpha-synuclein accumulation. beta-Synuclein,
      the nonamyloidogenic homologue of alpha-synuclein, has recently been identified
      as a potential candidate. Thus, in vivo transfer of genes encoding beta-synuclein
      might provide a novel approach to the development of experimental treatments for
      PD and DLB. To assess this possibility and to better understand the mechanisms
      involved, a lentiviral vector expressing human (h) beta-synuclein (lenti-beta
      synuclein) was tested in a transgenic (tg) mouse model of halpha-synuclein
      aggregation. This study showed that unilateral intracerebral injection of lenti
      beta-synuclein reduced the formation of halpha-synuclein inclusions and the
      accumulation of halpha-synuclein in synapses and ameliorated the
      neurodegenerative alterations in the tg mice. Both in vivo and in vitro
      coimmunoprecipitation and immunoblot experiments show that the mechanisms of beta
      synuclein neuroprotection involve binding of this molecule to halpha-synuclein
      and Akt, resulting in the decreased aggregation and accumulation of halpha
      synuclein in the synaptic membrane. Together, these data further support a role
      for beta-synuclein in regulating the conformational state of alpha-synuclein and
      suggest that this gene transfer approach might have potential for the development
      of alternative therapies for PD and DLB.

PMID- 15483671
TI  - Philadelphia (Ph1)-negative myeloid/natural killer cell precursor leukemia
      evolving during Ph1-positive chronic myelogenous leukemia: report of two cases.

PMID- 15483672
TI  - Increased mitochondrial biogenesis in primary leukemia cells: the role of
      endogenous nitric oxide and impact on sensitivity to fludarabine.
AB  - B cell chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in
      the Western hemisphere, yet many biological and molecular features of the disease
      remain undefined. CLL cells generate increased levels of radical species such as
      superoxide and nitric oxide (NO), which is associated with mitochondrial DNA
      mutations. Considering that NO levels can affect mitochondrial biogenesis, we
      hypothesized that the inherent nitrosative stress in CLL cells may lead to
      hyperactive mitochondrial biogenesis. Here we report that primary CLL cells
      contained significantly more mitochondria than normal lymphocytes and that their
      mitochondrial mass was significantly related to endogenous NO levels. Expression
      of the mitochondrial biogenesis factors nuclear respiratory factor-1 and
      mitochondrial transcription factor A was elevated in most CLL specimens examined
      and appeared to be related to cellular NO levels. Treatment of B cells with
      exogenous NO caused a substantial increase in mitochondrial mass. In vitro
      sensitivity of CLL cells to fludarabine was highly related to mitochondrial mass
      in that cells with greater mitochondrial mass were less sensitive to the drug.
      Taken together, our results suggest that NO is a key mediator of mitochondrial
      biogenesis in CLL and that modulation of mitochondrial biogenesis by NO may alter
      cellular sensitivity to fludarabine.

PMID- 15483673
TI  - Constitutive activation of the MAPkinase p38 is critical for MMP-9 production and
      survival of B-CLL cells on bone marrow stromal cells.
AB  - In the present work we investigated the role and biological significance of
      mitogen activated protein kinases (MAPK) in B-cell chronic lymphocytic leukaemia
      (B-CLL). The MAPK p38 was constitutively activated in B-CLL, but not in normal
      peripheral B cells. In addition, we demonstrated that the upstream kinases of
      p38, MKK3/6 were also constitutively activated in B-CLL cells. Furthermore, we
      determined by EMSA that the p38 MAP kinase pathway was not linked to the
      constitutive high expression of NF-kappaB, a critical survival factor of B-CLL
      cells. Recently, it has been shown that serum levels of angiogenic factors like
      VEGF, bFGF and MMP-9 are elevated in the serum of CLL patients and correlate with
      an unfavorable prognosis. We showed that the constitutive expression of MMP-9 was
      dependent on p38-activity and inhibition of p38 strongly downregulated MMP-9
      expression. Coculture of B-CLL cells and stromal cells can protect spontaneous
      apoptosis of leukemic B cells. To determine the role of permanently activated p38
      and MMP-9 expression, we cocultured B-CLL cells with bone marrow stromal cells.
      Survival of B-CLL cells on stroma was severely impaired when p38 was inhibited.
      Furthermore, blockade of MMP-9 activity also antagonized the antiapoptotic effect
      of stromal cells.

PMID- 15483674
TI  - Significant difference in outcome for adolescents with acute lymphoblastic
      leukemia treated on pediatric vs adult protocols in the Netherlands.

PMID- 15483675
TI  - Evidence of biased immunoglobulin variable gene usage in highly stable B-cell
      chronic lymphocytic leukemia.
AB  - Recognition of biased immunoglobulin variable (IgV) gene usage in B-cell chronic
      lymphocytic leukemia (B-CLL) may yield insight into leukemogenesis and may help
      to refine prognostic categories. We explored Ig variable heavy (VH) and light
      (VL) chain gene usage in highly stable and indolent B-CLL (n=25) who never
      required treatment over 10 or more years. We observed an unexpectedly high usage
      of mutated VH3-72 (6/25; 24.0%), a gene that was otherwise rare in B-CLL (7/805;
      0.87%; P<0.01), including mutated cases (6/432; 1.39%; P<0.01) and was
      exceptional among indolent (1/230, 0.435%; P<0.01), and aggressive B-cell
      lymphomas (0/105; P<0.01). Three of six VH3-72 B-CLL cases utilized the same VL
      Vkappa4-1 gene. Two V(H)3-72 B-CLL cases had highly homologous VH complementarity
      determining regions 3 (CDR3s), encoding Cys-XXXX-Cys domains, and utilized
      Vkappa4-1 genes with homologous IgVL CDR3s. An identical threonine to isoleucine
      change at codon 84 of V(H)3-72 framework region 3 (FR3) recurred in four cases of
      highly stable VH3-72 B-CLL. This mutation is expected to cause a conformational
      change of FR3 proximal to CDR3 that might critically affect high-affinity antigen
      binding. B-cell receptors encoded by VH3-72 may identify a specific B-CLL group
      and be implicated in leukemogenesis through an antigen-driven expansion of B
      cells.

PMID- 15483676
TI  - Cryptic ins(2;11) with clonal evolution showing amplification of 11q23-q25 either
      on hsr(11) or on dmin, in a patient with AML-M2.

PMID- 15483677
TI  - IgH DJ rearrangements within T-ALL correlate with cCD79a expression, an
      immature/TCRgammadelta phenotype and absence of IL7Ralpha/CD127 expression.
AB  - cCD79a and IgH VDJ/DJ rearrangements are considered to be relatively specific for
      B lymphoid precursors. We looked for both in cCD3+, CD7+, CD19- T-ALLs classified
      by TCR status into alphabeta or gammadelta/immature (IM) lineages, with
      individualization of HOX11L2+ T-ALLs since they represent an intermediate
      alphabeta/gammadelta category. cCD79a was expressed at low levels in 47% of T-ALL
      and was most frequent in IMgamma T-ALLs. IgH rearrangements were common in
      gammadelta/IM (45%) and HOX11L2+ (35%) T-ALLs compared to HOX11L2-negative cases
      (3%; P<0.001). CD127 (IL7Ralpha) expression was also more common in the
      gammadelta/IM lineage but its expression was virtually mutually exclusive of IgH
      rearrangement. Low-level cCD79a expression alone should therefore not be
      interpreted as evidence of B lineage affiliation in immature leukemias.
      gammadelta/IM lineage T-ALLs potentially include two distinct categories:
      predominantly IgH+, cCD79a+, CD127- cases which retain gammadelta and B lymphoid
      potential and IgH-, cCD79a-, CD127+ cases with restricted T lineage potential.

PMID- 15483678
TI  - Strategies for overcoming p-glycoprotein-mediated drug resistance in acute
      myeloblastic leukaemia.

PMID- 15483679
TI  - Caspase-dependent, geldanamycin-enhanced cleavage of co-chaperone p23 in leukemic
      apoptosis.
AB  - Co-chaperone p23 is a component of the heat-shock protein (Hsp)90 multiprotein
      complex and is an important modulator of Hsp90 activity. Hsp90 client proteins
      involved in oncogenic survival signaling are frequently mutated in leukemia, and
      the integrity of the Hsp90 complex could therefore be important for leukemic cell
      survival. We demonstrate here that p23 is cleaved to a stable 17 kDa fragment in
      leukemic cell lines treated with commonly used chemotherapeutic drugs. The
      cleavage of p23 paralleled the activation of procaspase-7 and -3 and was
      suppressed by the caspase-3/-7 inhibitor DEVD-FMK. In vitro translated 35S-p23
      (in reticulocyte lysate) was cleaved at D142 and D145 by caspase-7 and -3.
      Cleavage of p23 occurred in caspase-3-deficient MCF-7 cells, suggesting a role
      for caspase-7 in intact cells. The Hsp90 inhibitor geldanamycin enhanced caspase
      dependent p23 cleavage both in vitro and in intact cells. Geldanamycin also
      enhanced anthracycline-induced caspase activation and apoptosis. We conclude that
      p23 is a prominent target in leukemic cell apoptosis. Geldanamycin enhanced p23
      cleavage both by rendering p23 more susceptible to caspases and by enhancing
      chemotherapy-induced caspase activation. These findings underscore the importance
      of the Hsp90-complex in antileukemic treatment, and suggest that p23 may have a
      role in survival signaling.

PMID- 15483680
TI  - [5th Peruvian Congress of Hepatology].

PMID- 15483681
TI  - [Postoperative morbidity and in-hospital mortality of gastrectomy due to gastric
      adenocarcinoma: a report of 50 years].
AB  - OBJECTIVE: Determine the postoperative morbidity and in-hospital mortality of
      gastrectomy due to gastric cancer. METHOD: The study involved the review of the
      clinical records of all patients with histologically confirmed diagnostic of
      gastric adenocarcinoma, which underwent a gastrectomy at the Peruvian Institute
      of Neoplastic Diseases between January 1950 and December 1999. During that
      period, 2,033 gastrectomies were performed, 503 of which were total gastrectomies
      and 1,447 were distal subtotal gastrectomies. Postoperative morbidity of total
      and distal subtotal gastrectomy dropped from 23.7% and 14.3% during the 1950
      decade, to 19.8% and 7.4% during the 1990 decade, respectively, while the in
      hospital mortality of total and subtotal gastrectomy dropped from 28.9% and 19.4%
      during the 50s to 4.4% and 2.2% during the 90's. The most common complications
      were the esophagojejunal, gastrojejunal and duodenal fistulas, respiratory
      infections, intra-abdominal abscesses, pancreatic fistula, early intestinal
      obstruction, hemorrhage from the anastomosis site and surgical site infection.
      RESULTS: Multivariate logistics regression analysis showed that the risk factors
      for in-hospital mortality of total gastrectomy were hypoalbuminemia,
      intraoperative blood transfusion and re-resection (OR: 2.4, 5.9 and 1.7,
      respectively). For distal subtotal gastrectomy, the risk factors for in-hospital
      mortality were hypoalbuminemia, intraoperative blood transfusion, splenectomy and
      re-resection (OR: 2.6, 2.46, 2.42 and 6.3, respectively). CONCLUSIONS: Based on
      our results, the in-hospital mortality risk depends on the postoperative
      variables (hypoalbuminemia, intraoperative blood transfusion, splenectomy and re
      resection) more than on the pre-operative variables, beyond the surgeon's control
      (age, sex, clinical stage, etc.).

PMID- 15483682
TI  - [Factors associated with postoperative mortality following gastric adenocarcinoma
      surgery at the Edgardo Rebagliati Martins Hospital].
AB  - OBJECTIVES: This study is a retrospective, descriptive and observational
      evaluation aimed at defining the factors associated with postoperative mortality
      due to gastric adenocarcinoma and evaluating postoperative morbidity at the
      Edgardo Rebagliati Martins Hospital. METHODS: The study included 282 patients,
      which had undergone surgery between January 1, 1996 and December 31, 1999 and the
      evaluation involved filiation, background, tumor location, Bormann and Early
      Cancer classifications, histological classification, number of resected lymphatic
      nodes, extragastric compromise, type of surgery and reconstruction, TNM
      classification, clinical stage and medical and surgical complications. RESULTS:
      Patients were divided in two groups: Survivors (n=251) and deceased (n=31)
      evidencing 31.56% morbidity and 10.99% mortality. The factors associated with
      mortality were: age, hypertension (AHT), cardiopathy, tumor location in the
      stomach, extragastric compromise of the liver, T3 and T4 tumors, N1, distant
      metastases, clinical stage IV, pneumonia and other surgical complications.
      CONCLUSIONS: These results lead us to conclude that proper preoperative staging
      of the disease is necessary and so is special care with patients suffering of
      hypertension, diabetes and cardiopathy.Finally, we consider it pertinent to bear
      in mind the postoperative complications, for proper management of them.

PMID- 15483683
TI  - [Variation of Helicobacter pylori prevalence and its relation with the level of
      chlorine in the water at the "Atarjea" plant, Lima, Peru. Period 1985-2002].
AB  - OBJECTIVES: Relate the variation in the prevalence of Helicobacter pylori in
      patients from medium and high socio-economic levels, suffering from chronic
      active gastritis (CAG) and peptic ulcer, from 1985 to 2002, in Lima, Peru with
      the content levels of chlorine in the water at the "Atarjea" Water Treatment
      Plant. MATERIALS AND METHODS: A total of 1,815 patients showing upper
      gastrointestinal tract symptoms were examined by esophago-gastro-duodenoscopy,
      excluding those patients who during the past four weeks had been treated with
      antibiotics, H2 receptor blockers and proton pump inhibitors. The variation of
      the H. pylori infection prevalence was compared to the content levels of chlorine
      in the water at the "Atarjea" plant. RESULTS: A total of 1,290 patients with CAG
      were identified; 178 with duodenal ulcer; 55 with gastric ulcer and 292 with
      histologically normal gastric mucose (HNGM). The prevalence of H. pylori in
      patients with CAG dropped from 83.3% to 58.7% (p<0.001). In patients with
      duodenal ulcer, it decreased from 89.5% to 71.9% (p=0.004) and in those with
      gastric ulcer, from 84.8% to 77.3% (p=0.36). In patients with HNGM prevalence
      remained the same (from 2.7% to 0.0%) (p=0.15). The chlorine content levels at
      the water of "Atarjea" plant remained relatively stable from 1991 to 2000. No
      correlation was found with the prevalence of Helicobacter pylori (p>0.05).
      CONCLUSIONS: Between 1985 and 2002, prevalence of Helicobacter pylori with
      chronic active gastritis (CAG) and/or peptic ulcer in patients from the medium
      and upper socio-economic strata, diminished. No correlation was found between the
      chlorine content levels in the water treated at the "Atarjea" plant and the
      decrease of this prevalence.

PMID- 15483684
TI  - [Seroprevalence of Helicobacter pylori among the child population of Ecuador].
AB  - OBJECTIVES: To determine the prevalence of anti-Helicobacter pylori IgG
      antibodies among the children population of Ecuador and the possible relation
      with the presence of recurring gastrointestinal symptoms. MATERIALS AND METHODS:
      Children randomly selected from different geographical areas were included and
      the presence of serum antibodies was tested using the enzyme-linked immunosorbent
      assay (ELISA). The gastrointestinal symptoms between patients with serum
      antibodies and those without serum antibodies were analyzed, excluding children
      who had not been treated for intestinal parasites before. RESULTS: A total of 257
      children was studied, with a mean age of 8.3 years (age range between 6 months
      and 16 years). A seroprevalence of 63.03% was found, the most affected being the
      children from the Andes mountains, in the range 0 to 4 years old. A significant
      relation was found between the presence of anti-Hp antibodies and symptoms
      (p=0.001). CONCLUSIONS: There is a high prevalence of anti-Helicobacter pylori
      IgG antibodies among the Ecuadorian children, related with the presence of
      recurring gastrointestinal symptoms.

PMID- 15483685
TI  - [Colon and rectum signet-ring cell carcinoma in the National Institute of
      Neoplastic Diseases].
AB  - OBJECTIVE: Primary signet ring cell carcinoma of the colon and rectum is a rare
      form of adenocarcinoma of the large intestine. The purpose of this study was
      define the incidence, natural history and relation with hereditary nonpolyposis
      colorectal cancer (HNPCC). METHODS: We reviewed the medical records and pathology
      of 28 patients with primary signet ring cell carcinoma of the colon and rectum
      seen at the Instituto de Enfermedades Neoplasicas (INEN), between 1991 and 2002.
      RESULTS: In the present study the incidence was 5.09% of large bowel
      adenocarcinoma. Most patients present with late stage disease (Dukes stage C and
      D). In most cases the signet ring cells diffusely infiltrated through all layers
      of the intestinal wall (Borrmann IV). Male to female ratio was of 1 : 1.5, mean
      age was 55.5 and median age was 57 years (range 11 - 83 years). CONCLUSIONS:
      Comparison of our data with the literature showed some differences that could be
      related with biological characteristics of our people and different applied
      inclusion criteria. We couldn't define the relation between HNPCC and primary
      signet ring cell carcinoma of the colon and rectum.

PMID- 15483686
TI  - [Primary gastric lymphoma].
AB  - INTRODUCTION: Primary Gastric Lymphoma is an uncommon malignancy among gastric
      malignancies. Histology of the Primary Gastric Lymphoma is varied and the
      extranodal marginal zone B-cells lymphoma is specially significant on account of
      its potential remission with antibiotic therapy. OBJECTIVES: Observe the clinical
      characteristics of patients with Primary Gastric Lymphoma, assess the most
      relevant endoscopic findings, identify the factors that influence survival and
      evaluate the effects of therapy. MATERIALS AND METHODS: The study is an
      observational, analytical, cross evaluation including 169 patients with
      histological diagnosis of Gastric Lymphoma, treated at the National Institute for
      Neoplastic Diseases, Lima, Peru, from January 1995 to December 2000. Staging was
      based on the Ann Arbor system, modified by Musshoff and histology, on the REAL
      WHO classification. The statistical analysis included the student-t and the chi
      square tests. Survival data were entered using the Kaplan Meier curves and
      prognosis factors, using the Cox regression test. RESULTS: The sample represents
      patients from the Peruvian Coast, with a mean age of 55 years old and slight
      predominance of female patients (54.4%). Signs and symptoms are unspecific.
      Clinical stage I-II corresponds to 75% of the patients. The endoscopic pattern of
      multiple ulcerated lesions is characteristic of the Gastric Lymphoma. A total of
      71% of the patients with extranodal marginal zone B-cells lymphoma showed total
      remission of the disease with antibiotic therapy (5/7). The histological type of
      the Gastric Lymphoma in the 169 patients was as follows: Large, diffuse, B-cells
      Lymphoma, 137 patients, extranodal marginal zone B-cells lymphoma, 16 patients,
      peripheral T-cell Lymphoma, 6 patients, anaplastic large T-cell Lymphoma, 3
      patients, undetermined Lymphoma, 3 patients, mantle cell Lymphoma, 2 patients,
      adult T-cell Lymphoma, 1 patient and follicular Lymphoma, 1 patient. Global
      survival after 36 months was of 61.34%, survival according to the histological
      type was of 92.31% for extranodal marginal zone B-cells Lymphomas, 62.21% for
      large, diffuse B-cells Lymphomas and 29.63% for T-cell Lymphomas. Survival after
      36 months in patients in clinical stage I-II treated with chemotherapy, was of
      82.16%, with surgery, 71.89% and with surgery and chemotherapy, 70.39, with
      similar results in all three groups (p: 0.6530). The groups classified according
      to the international index, showed a clear difference between them (p:0.0000).
      The univariate analysis revealed that Zubrod (p:0.0000) DHL (p:0.0073) disease
      remission (p:0.0000) stage (p:0.0000) treatment (p:0.0000) and location
      (p:0.0000) had statistical significance. Multivariate analysis showed that in the
      Cox regression model, remission (OR:13,342, p:0.0000) and location (OR:2.375,
      p:0.041) fall within the equation of such function. CONCLUSIONS: The multiple
      ulcerated lesions are characteristic of the Gastric Lymphoma. Remission of the
      disease in the extranodal marginal zone B-cells Lymphoma is evidenced with the
      use of antibiotic therapy (5/7). Chemotherapy in patients with EC I-II achieves
      survival results similar to those treated with surgery and with a combination of
      both. Validity of the international index is confirmed and the multivariate
      analysis proved that remission and location of the disease have statistical
      significance.

PMID- 15483687
TI  - Basic and clinical aspects of Clostridium difficile colitis.
AB  - Clostridium difficile, a gram-positive anaerobic bacillus dubbed as the difficult
      clostridium because it resisted early attempts of isolation and culture. After
      some decades in the darkness, it became famous, when in 1978, a cytotoxin of the
      C. difficile was found the responsible of the pseudomembranous colitis. We review
      in this paper aspects of the epidemiology of the C. difficile in health and
      disease. Also the importance of C. difficile as a cause of nosocomial infections.
      We review the characteristics of the toxins A and B produced by the pathogenic
      strains of C. difficile. Finally, clinical aspects of infection with C. difficile
      in special in the pseudomembranous colitis. The diagnosis, medical therapy,
      complications and surgical indications are briefly described.

PMID- 15483688
TI  - [Argon laser endoscopy therapy in refractory bleeding post sphynterotomy: report
      of two cases].
AB  - We report two cases of successfully endoscopy therapy with argon plasma in upper
      gastrointestinal bleeding secondary a complication of endoscopic sphynterotomy,
      who fails to previous injectotherapy attempts. The bleeding control was complete
      and without complications.

PMID- 15483689
TI  - [Mixed cryoglobulinemia and related immunological disorders after hepatic
      transplantation for hepatitis C cirrhosis. Case report].
AB  - Cryoglobulinemia may be found in up to 30% of patients that had received liver
      transplants after hepatitis C virus (HCV) cirrhosis. Three types of
      cryoglobulinemia are recognized: type I, composed of monoclonal immunoglobulins
      associated with lymphoproliferative diseases and myeloma; type II
      cryoglobulinemia are comprised of a monoclonal component which has rheumatoid
      factor activity and hence binds to polyclonal immunoglobulins (in certain parts
      of the world have been found to be associated with hepatitis C infection); and
      type III cryoglobulinemia consist exclusively of polyclonal immunoglobulins with
      rheumatoid factor activity (associated with connective tissue diseases and
      chronic infections including hepatitis C). Immunocompetence, autoimmunity and
      clonal expansion of B cell lymphocytes have not been analysed simultaneously in
      previous reports of patients with cryoglobulinemia after liver transplantation.
      We here describe immunological abnormalities associated with cryoglobulinemia in
      a patient who had received liver transplant for HCV cirrhosis. In addition, in
      the present work HCV RNA determination was performed directly in the cryocrit and
      not only in peripheral blood. We have observed enrichment of HCV RNA in the
      cryoprecipitates which might be a better demonstration of the possible role of
      HCV in the pathogenesis of the cryoglobulinemia.

PMID- 15483690
TI  - Quantum chemical studies of dioxygen activation by mononuclear non-heme iron
      enzymes with the 2-His-1-carboxylate facial triad.
AB  - Density functional theory with the B3LYP hybrid functional has been used to study
      the mechanisms for dioxygen activation by four families of mononuclear non-heme
      iron enzymes: alpha-ketoacid-dependent dioxygenases, tetrahydrobiopterin
      dependent hydroxylases, extradiol dioxygenases, and Rieske dioxygenases. These
      enzymes have a common active site with a ferrous ion coordinated to two
      histidines and one carboxylate group (aspartate or glutamate). In contrast to the
      heme case, this type of weak field environment always leads to a high-spin ground
      state. With the exception of the Rieske dioxygenases, which have an electron
      source outside the active site, the dioxygen activation process passes through
      the formation of a bridging-peroxide species, which then undergoes O-O bond
      cleavage finally leading to the four electron reduction of O(2). In the case of
      tetrahydrobiopterin- and alpha-ketoacid-dependent enzymes, the O-O heterolysis
      yields a high-valent iron-oxo species, which is capable of performing a two
      electron oxidation chemistry on various organic substrates. For the other two
      families of enzymes (extradiol dioxygenases and Rieske dioxygenases) the
      substrate oxidation and the O-O bond cleavage are found to be coupled. In the
      extradiol dioxygenases the product of the O-O bond cleavage is a ferric iron with
      an oxy-substrate with a mixture of radical and anionic character, which is
      essential for the selectivity of the catechol cleavage.

PMID- 15483691
TI  - Rare and unexpected coordination to copper(II) by a tertiary amide in a
      macrocyclic ligand.
AB  - Incorporation of a tertiary amide donor within the framework of a C(2)-symmetric
      analogue of 1,4,7-triazacyclononane derived from L-valine results in the
      isolation of a very rare example of a classical Werner copper(II) complex in
      which tertiary amide coordination occurs; despite the monomeric nature of the
      complex in the solid state, frozen solution EPR studies reveal the presence of a
      triplet ground state consistent with a dimeric species.

PMID- 15483692
TI  - Solution- and solid-state characterisation of a configurationally-stable beta
      diketiminato-supported calcium primary amide.
AB  - 'Selective' protonolysis of the beta-diketiminato calcium derivative
      [Ca[(NDippCMe)(2)CH][N(SiMe(3))(2)](THF)] Dipp = C(6)H(3)(i)Pr(2)-2,6) with
      H(2)N(CH(2))(2)OCH(3) produced the dimeric species [Ca[(NDippCMe)(2)CH][mu
      NH(CH(2))(2)OMe]](2), which has been fully characterised in solution and in the
      solid state.

PMID- 15483693
TI  - A new synthetic route to metal trithiophosphonates: syntheses and structures of
      [(C6H11)PS3Li2).THF.TMEDA]2 and [(C6H11))PS3Mg.2THF]2.
AB  - A new synthesis for trithiophosphonates from primary phosphines, nBuLi (or
      nBu(2)Mg) and elemental sulfur is presented and its mechanism investigated; the
      lithium and magnesium salts of cyclohexyltrithiophosphonate have been fully
      characterised to reveal dimers in the solid state in which all three of the
      trithiophosphonate sulfurs are involved in metal bonding.

PMID- 15483694
TI  - The reaction of RhCp*(CH3)2(L)(L = pyridine, dmso) with GaCp* and AlCp*: a new
      type of carbon-carbon bond activation reaction.
AB  - Reaction of RhCp*(L)(CH(3))(2)(L = pyridine, dmso) with equimolar amounts of
      GaCp* at 60 degrees C quantitatively leads to the zwitterionic species
      [Cp*Rh(CpMe(4)GaMe(3))]. [Cp*Rh(CH(3))(2)(GaCp*)] could be isolated and
      identified as an intermediate in this reaction.

PMID- 15483695
TI  - Anomalous structure-luminescence relationship in phosphorescent gold(I)
      isonitrile neutral complexes.
AB  - A new compound that exhibits the shortest intermolecular Au...Au distance ever
      reported for neutral RNCAuX complexes is found to exhibit a counterintuitive
      higher-energy Au-centered phosphorescence than that in an analogous compound with
      a much longer Au...Au distance, presumably due to a different extent of excited
      state distortion in dimers vs. extended chains.

PMID- 15483696
TI  - Metal-induced formation of a new chiral bidentate N,O ligand and the synthesis of
      novel monomeric germylenes.
AB  - Lithiation of the N-benzyl substituted diketoamine ligand PhCH(2)
      N[CH(2)C(tBu=O](2) with lithium diisopropylamide (LDA) affords a novel chiral
      anionic N,O-ligand L; LiL reacts with GeCl(2).dioxane to give the corresponding
      new monomeric germylenes LGeCl and L(2)Ge.

PMID- 15483697
TI  - Intramolecular reduction of the nitro group into phosphoraneimine mediated by a
      rhenium(v) complex. Synthesis and structure of the novel phosphoraneimine
      oxorhenium(v) complex [ReOCl[o-(PPh3=N)C6H4(NCH2CH2N(CH2CO2H)CH2CO2]].
AB  - The title compound was synthesised via an unexpected intramolecular reduction of
      a nitro group in the oxo-Re(v) coordination sphere.

PMID- 15483698
TI  - New route to a face-to-face biscorrole free-base and the corresponding
      heterobimetallic copper(III)-silver(III) complex.
AB  - A meso-aryl-substituted face-to-face biscorrole was synthesised in a two-step
      reaction and the corresponding homo- and heterobimetallic complexes were obtained
      and fully characterised.

PMID- 15483699
TI  - The ruthenium(II)-supported heteropolytungstates [Ru(dmso)3(H2O)-XW11O39]6- (X =
      Ge, Si).
AB  - The novel Ru(II)-supported heteropolytungstates [Ru(dmso)(3)(H(2)O)XW(11)O(39)](6
      )(X = Ge, Si) have been synthesized and characterized by single-crystal X-ray
      diffraction, multinuclear NMR ((183)W, (13)C, (1)H, (29)Si) and IR spectroscopy,
      elemental analysis and electrochemistry. The novel polyanion structure consists
      of a Ru(dmso)(3)(H(2)O) unit linked to a monolacunary [XW(11)O(39)](8-) Keggin
      fragment via two Ru-O-W bonds resulting in an assembly with C(1) symmetry.
      Polyanions 1 and 2 were synthesized by reaction of cis-Ru(dmso)(4)Cl(2) with [A
      alpha-XW(9)O(34)](10-) in aqueous, acidic medium (pH 4.8). Tungsten-183 NMR of 1
      leads to a spectrum with 11 peaks of equal intensity, indicating that the solid
      state structure is preserved in solution. Electrochemistry studies revealed that
      1 and 2 are stable in solution at least from pH 0 to 7, even in the presence of
      dioxygen. Their cyclic voltammetry patterns show mainly two two-electron
      reversible W-waves, those of the Si derivative 2 being located at slightly more
      negative potentials than those of the Ge derivative 1. The observed stability of
      1 and 2 might be attributed to a stabilization of the Ru-center both by the
      strongly bound dmso ligands and the Keggin moiety. This stabilization drives the
      redox waves of Ru outside the accessible potential range. However, conditions
      were found to reveal, at least partially, the redox behavior of Ru in 1 and 2.

PMID- 15483700
TI  - XAS characterization of end-on and side-on peroxoiron(III) complexes of the
      neutral pentadentate N-donor ligand N-methyl-N,N',N'-tris(2-pyridylmethyl)ethane
      1,2-diamine.
AB  - Peroxo intermediates are implicated in the catalytic cycles of iron enzymes
      involved in dioxygen metabolism. X-ray absorption spectroscopy has been used to
      gain insight into the iron coordination environments of the low-spin complex
      [Fe(III)(Me-TPEN)(eta(1)-OOH)](2+)(1) and the high-spin complex [Fe(III)(Me
      TPEN)(eta(2)-O(2))](+)(2)(the neutral pentadentate N-donor ligand Me-TPEN =N
      methyl-N,N',N'-tris(2-pyridylmethyl)ethane-1,2-diamine) and obtain metrical
      parameters unavailable from X-ray crystallography. The complexes exhibit
      relatively large pre-edge peak areas of approximately 15 units, indicative of
      iron centers with significant distortions from centrosymmetry. These distortions
      result from the binding of peroxide, either end-on hydroperoxo for 1 (r(Fe-O)=
      1.81A) or side-on peroxo for 2 (r(Fe-O)= 1.99 A). The XAS analyses of 1 strongly
      support a six-coordinate low-spin iron(III) center coordinated to five nitrogen
      atoms from Me-TPEN and one oxygen atom from an end-on hydroperoxide ligand.
      However, the XAS analyses of 2 are not conclusive: Me-TPEN can act either as a
      pentadentate ligand to form a seven-coordinate peroxo complex, which has
      precedence in the DFT geometry optimization of [Fe(III)(N4Py)(eta(2)
      O(2))](+)(the neutral pentadentate N-donor ligand N4Py =N,N-bis(2-pyridylmethyl)
      N-bis(2-pyridyl)methylamine), or as a tetradentate ligand with a dangling
      pyridylmethyl arm to form a six-coordinate peroxo complex, which is precedented
      by the crystal structure of [Fe(2)(III)(Me-TPEN)(2)(Cl)(2)(mu-O)](2+).

PMID- 15483701
TI  - Designing copper(II) ternary complexes to generate radical cations of peptides in
      the gas phase: role of the auxiliary ligand.
AB  - A series of ternary copper(II) complexes of the type [Cu(II)(L)(M)](2+), where M
      represents the hexapeptides GGGFLR, YGGFLR and WGGFLR and L a set of 12 nitrogen
      donor ligands have been evaluated for their ability to form cationic peptide
      radicals, M(+)*, in the gas phase. Although the fragmentation chemistry of these
      ions is complex, two main conclusions emerge: (i) Complexes containing a tri- or
      tetra-dentate ligand were found to be more effective at producing the peptide
      radical because in these instances competitive loss of the ligand from the
      complex is inhibited; (ii) The ligands ought not possess any acidic protons in
      order to prevent competitive loss of the protonated peptide, [M + H](+). There is
      significant interaction of the N-terminal aromatic residues in YGGFLR and WGGLFR
      with the copper(ii) ion in several of the complexes as revealed by the formation
      of [Cu(I)(L)(p-quinomethide)](+) and [Cu(I)(L)(3-methyleneindoline)](+) fragment
      ions. Following its dissociation from the ternary complex, CID of the YGGFLR(+)*
      radical cation shows a dependence on the ligand in the complex from which it was
      formed. This 'memory effect' most likely reflects differences in the coordinated
      peptide structure induced by the ligand in the precursor complex which are
      maintained following dissociation.

PMID- 15483702
TI  - Influence of the coordination geometry on the physicochemical properties of a
      copper(II) complex with a tailor-made calixarene-based ligand bearing dipyridyl
      pendants. An ESR, UV-Vis and CV study.
AB  - Dipyridyl pendants, suitably attached onto a calix[4]arene fixed in its 1,3
      alternate conformation, form stable complexes with copper(ii) in acetonitrile.
      Both the mononuclear and the homobinuclear species ([Cu(1)](2+) and
      [Cu(2)(1)](4+)), previously detected through a UV-Vis investigation, have been
      studied by ESR, UV-Vis and cyclic voltammetry. ESR and UV-Vis data clearly
      indicate that in the [Cu(1)](2+) species the nitrogen atoms of dipyridyl pendants
      are tetrahedrally arranged around copper(II). Computer models, optimised through
      molecular mechanics methods, further support these spectroscopic findings. The
      tetrahedral arrangement, achieved thanks to the anchoring of the dipyridyl
      moieties onto the calixarene platform, accounts for the easy reversible reduction
      of this species. The aspects associated with the reduction-oxidation of the
      homobinuclear species are also discussed.

PMID- 15483703
TI  - Silver cages with encapsulated acetylenediide as building blocks for hydrothermal
      synthesis of supramolecular complexes with n-cyanopyridine and pyridine-n
      carboxamide (n=3, 4).
AB  - New silver(i) double salts (Ag(2)C(2))(AgCF(3)CO(2))(8)(3-pyCONH(2))(2)(H(2)O)(4)
      (1), [(Ag(2)C(2))(AgCF(3)CO(2))(4)(4-pyCONH(2))(H(2)O)].H(2)O (2),
      (Ag(2)C(2))(AgCF(3)CO(2))(6)(3-pyCONH(2))(4) (3), (Ag(2)C(2))(AgCF(3)CO(2))(6)(3
      pyCN)(2) (4) and (Ag(2)C(2))(AgCF(3)CO(2))(4)(4-pyCN)(2) (5) (n-pyCONH(2) is
      pyridine-n-carboxamide, n-pyCN is n-cyanopyridine; n=3, 4) have been synthesized
      by the hydrothermal method. All five compounds contain polyhedral silver(i) cages
      each encapsulating a C(2)(2-) dianion. Compounds 1, 3 ,4 and 5 exhibit three
      dimensional structures, whereas compound 2 is a two-dimensional network. The
      structure of 1 is constructed from the linkage of a branched-tree architecture
      via hydrogen bonds. Unlike 4 and 5, which involve the connection of n
      cyanopyridine (n=3, 4) with silver columns, 3 results from the linkage of
      discrete silver cages via pyridine-3-carboxamide.

PMID- 15483704
TI  - The reaction of M(CO)3(Ph2PCH2CH2PPh2)(M = Fe, Ru) with parahydrogen: probing the
      electronic structure of reaction intermediates and the internal rearrangement
      mechanism for the dihydride products.
AB  - The photochemical reaction of Ru(CO)(3)(dppe) and Fe(CO)(3)(dppe)(dppe =
      Ph(2)PCH(2)CH(2)PPh(2)) with parahydrogen has been studied by in situ
      photochemistry resulting in NMR spectra of Ru(CO)(2)(dppe)(H)(2) that show
      significant enhancement of the hydride resonances while normal signals are seen
      in Fe(CO)(2)(dppe)(H)(2). This effect is associated with a singlet electronic
      state for the key intermediate Ru(CO)(2)(dppe) while Fe(CO)(2)(dppe) is a
      triplet. DFT calculations reveal electronic ground states consistent with this
      picture. The fluxionality of Ru(CO)(2)(dppe)(H)(2) and Fe(CO)(2)(dppe)(H)(2) has
      been examined by NMR spectroscopy and rationalised by theoretical methods which
      show that two pathways for ligand exchange exist. In the first, the phosphorus
      and carbonyl centres interchange positions while the two hydride ligands are
      unaffected. A second pathway involving interchange of all three ligand sets was
      found at slightly higher energy. The H-H distances in the transition states are
      consistent with metal-bonded dihydrogen ligands. However, no local minimum
      (intermediate) was found along the rearrangement pathways.

PMID- 15483705
TI  - Acetylene to vinylidene rearrangements on electron rich d6 metal centers: a
      density functional study.
AB  - The acetylene to vinylidene isomerization on several Ru(II) d(6) metal fragments
      with different electron richness of the metal center has been investigated by
      means of density functional theory calculations. We considered the [(eta(5)
      C(5)Me(5))Ru(dippe)](+), [(eta(5)-C(5)Me(5))Ru(dmpe)](+), [(eta(5)
      C(5)H(5))Ru(PMe(3))(2)](+), [(eta(6)-C(6)Me(6))(PMe(3))ClRu](+), [(eta(5)
      C(5)H(5))Ru(CO)(PPh(3))](+) and [eta(6)-C(6)H(6))(PMe(3))ClRu](+), species which
      are quite common in the chemistry of cationic Ru(II) complexes and span a wide
      range of electron-richness. For each of the considered fragments, the minima on
      the potential energy surfaces for the two possible isomerization mechanisms, i.e.
      through a direct 1,2-hydrogen shift or through a hydrido-alkynyl intermediate,
      have been localized. A linear correlation has been found between the C=C
      stretching frequencies of the vinylidene complexes, as an estimate of the
      electron richness, and the stability of the corresponding hydrido-alkynyl
      intermediates. For the most electron-rich among the considered fragments,
      [(Cp*)(dippe)Ru(HCCH)](+), the hydrido-alkynyl species has been found essentially
      isoenergetic with the alkyne complex (only 1.9 kcal mol(-1) higher), in agreement
      with the experimental evidence showing for this system an equilibrium between
      these two species. For the same [(Cp*)(dippe)Ru](+) fragment, a detailed analysis
      of the reaction profiles for the two possible acetylene rearrangement pathways
      has been performed. Our results show that once the eta(2)-C-H coordinated
      acetylene intermediate is accessed, the system can easily evolve towards a
      hydrido-alkynyl intermediate, this process being kinetically favored with respect
      to the direct 1,2-shift leading to the vinylidene product.

PMID- 15483706
TI  - Flexible N,N,N-chelates as supports for iron and cobalt chloride complexes;
      synthesis, structures, DFT calculations and ethylene oligomerisation studies.
AB  - The aryl-substituted N-picolylethylenediamine and diethylenetriamine ligands,
      (ArNHCH(2)CH(2))[(2-C(5)H(4)N)CH(2)]NH and (ArNHCH(2)CH(2))(2)NH (Ar = 2,6
      Me(2)C(6)H(3), 2,4,6-Me(3)C(6)H(2)), have been prepared by employing palladium
      catalysed N-C(aryl) coupling reactions of the corresponding primary amines with
      aryl bromide. Treatment of MCl(2) with (ArNHCH(2)CH(2))[(2-C(5)H(4)N)CH(2)]NH
      affords [[(ArNHCH(2)CH(2))((2-C(5)H(4)N)CH(2))NH]CoCl(2)](Ar = 2,6-Me(2)C(6)H(3)
      1a; 2,4,6-Me(3)C(6)H(2)) 1b and [[(ArNHCH(2)CH(2))((2
      C(5)H(4)N)CH(2))NH]FeCl(2)](n)(n= 1, Ar = 2,6-Me(2)C(6)H(3) 2a; n= 2, 2,4,6
      Me(3)C(6)H(2) 2b) in high yield. The X-ray structures of 1a and 1b are
      isostructural and reveal the metal centres to adopt distorted trigonal
      bipyramidal geometries with the N,N,N-chelates adopting fac-structures. A facial
      coordination mode of the ligand is also observed in bimetallic 2b, however, in 2a
      the N,N,N-chelate adopts a mer-configuration with the metal centre adopting a
      geometry best described as square pyramidal. Solution studies indicate that mer
      fac isomerisation is a facile process for these systems at room temperature.
      Quantum mechanical calculations (DFT) have been performed on 1a and 2a, in which
      the ligands employed are identical, and show the fac- to be marginally more
      stable than the mer-configuration for cobalt (1a) while for iron (2a) the
      converse is evident. Reaction of (ArNHCH(2)CH(2))(2)NH with CoCl(2) gave the five
      coordinate complexes [[(ArNHCH(2)CH(2))(2)NH]CoCl(2)](Ar = 2,6-Me(2)C(6)H(3) 3a,
      2,4,6-Me(3)C(6)H(2) 3b), in which the ligand adopts a mer-configuration; no
      reaction occurred with FeCl(2). All complexes 1-3 act as modest ethylene
      oligomerisation catalysts on activation with excess methylaluminoxane (MAO); the
      iron systems giving linear alpha-olefins while the cobalt systems give mixtures
      of linear and branched products.

PMID- 15483707
TI  - The structure of aqueous pentaoxo silicon complexes with cis-1,2
      dihydroxycyclopentane and furanoidic vicinal cis-diols.
AB  - Addition of cis-1,2-dihydroxycyclopentane to aqueous alkaline silicate solutions
      results in the spontaneous formation of three organosilicate species, each with a
      2:1 ligand to Si ratio and a pentacoordinated silicon centre. By using a mixture
      of both cis-1,2-dihydroxycyclopentane and 1,4-anhydroerythritol we show
      unambiguously that all three species are diastereomers of the monomeric
      bis(diolato)-hydroxo complex, [(L=)(2)SiOH](-)(where L represents the cis-diol
      ligand), thus clarifying the general assignment of (29)Si NMR spectra reported
      for silicate solutions containing furanoidic sugars with vicinal cis-diol
      functionality, such as ribose.

PMID- 15483708
TI  - A family of oxorhenium(v) complexes incorporating chelated monoanionic ONN
      reduced Schiff base and dianionic ONNO tetradentate ligands: synthesis,
      spectroscopic and electrochemical studies.
AB  - The green colored complexes of the type Re(V)O(L(SB))Cl(2), 1, have been
      synthesised by reacting NBu(4)[ReOCl(4)] with HL(SB) in dry ethanol. Here, L(SB)(
      ) are the deprotonated forms of N-(2-hydroxybenzyl)-2-picolylamine (HL(SB)(1)); N
      (2-hydroxybenzyl)-N',N'-dimethylethylenediamine (HL(SB)(2)) and N-(2
      hydroxybenzyl)-N',N'-diethylethylenediamine (HL(SB)(3)). Similarly,
      NBu(4)[ReOCl(4)] reacted with N,N-bis(2-hydroxybenzyl)-2-picolylamine (H(2)L(1));
      N,N-bis(2-hydroxybenzyl)-N',N'-dimethylethylenediamine (H(2)L(2)); N,N-bis(2
      hydroxybenzyl)-N',N'-diethylethylenediamine (H(2)L(3)); [N-(2-hydroxybenzyl)-N-(2
      pyridylmethyl)]-2-aminoethanol (H(2)L(4)); [N-(2-hydroxybenzyl)-N-(2
      pyridylmethyl)]-2-methyl-2-amino-1-propanol (H(2)L(5)); N,N-bis(1-hydroxyethyl)-2
      picolylamine (H(2)L(6)), to give the monochloro complexes Re(V)O(L)Cl, 2. The X
      ray structures of the complexes are reported. The molecular structures observed
      in the solid state are preserved in solution ((1)H NMR). In acetonitrile solution
      the Re(V)O(L)Cl, 2, display a one-electron couple, Re(VI)O(L)Cl(+)-Re(V)O(L)Cl,
      near 1.0 V vs SCE. The electrogenerated hexavalent complexes
      [Re(VI)O(L)Cl]ClO(4), 3, are paramagnetic and display sextet EPR spectra in
      solution at room temperature (A(av) approximately 417 (G), g approximately
      1.914).

PMID- 15483709
TI  - Palladium(II) complexes of new OPN phosphine ligands and their application in
      homogeneously catalysed reactions of CO with alkenes or alkynes.
AB  - Palladium complexes of a series of functionalised phosphines bearing the OPN
      donor set [2-pyCH(2)P(Ph)CH(2)(CHOCH(2)CH(2)CH(2)), 1; 2-py CH(2)P(Ph)
      CH(2)CH(2)(CHOCH(2)CH(2)O), 2; 2-pyCH(2)P(Ph)CH(2)CH(2)CO(2)Me, 3; 2
      pyP(Ph)CH(2)(CHOCH(2)CH(2)CH(2)), 4; 2-py = 2-pyridyl] have been prepared and
      characterised. Ligands 1-3 form five membered P-N chelates which is confirmed for
      PdCl(2) complexes of and by X-ray crystallography. O-coordination appears to be
      generally disfavoured although there is evidence of transient O-coordination for
      selected Pd complexes of 4. Palladium methyl and acetate complexes of all four
      ligands have been tested for catalytic activity in ethene/CO copolymerisation as
      well as alkoxy-carbonylation of propyne. Complexes of 1 and 4 show some activity
      in the copolymerisation reaction and complexes of 4 are active in the methoxy
      carbonylation of propyne. Unlike related pyridyl(diaryl)phosphines, 4 produces a
      much more stable catalyst system that does not require large excesses of ligand
      to maintain activity.

PMID- 15483710
TI  - Spectroscopic characterization of the oxo-transfer reaction from a bis(mu
      oxo)dicopper(III) complex to triphenylphosphine.
AB  - The oxygen-atom transfer reaction from the bis(mu-oxo)dicopper(III) complex
      [Cu(III)(2)(mu-O)(2)(L)(2)](2+), where L =N,N,N',N' -tetraethylethylenediamine,
      to PPh(3) has been studied by UV-vis, EPR, (1)H NMR and Cu K-edge X-ray
      absorption spectroscopy in parallel at low temperatures (193 K) and above. Under
      aerobic conditions (excess dioxygen), 1 reacted with PPh(3), giving O=Ph(3) and a
      diamagnetic species that has been assigned to an oxo-bridged dicopper(II) complex
      on the basis of EPR and Cu K-edge X-ray absorption spectroscopic data. Isotope
      labeling experiments ((18)O(2)) established that the oxygen atom incorporated
      into the triphenylphosphine oxide came from both complex 1 and exogenous
      dioxygen. Detailed kinetic studies revealed that the process is a third-order
      reaction; the rate law is first order in both complex 1 and triphenylphosphine,
      as well as in dioxygen. At temperatures above 233 K, reaction of 1 with PPh(3)
      was accompanied by ligand degradation, leading to oxidative N-dealkylation of one
      of the ethyl groups. By contrast, when the reaction was performed in the absence
      of excess dioxygen, negligible substrate (PPh(3)) oxidation was observed.
      Instead, highly symmetrical copper complexes with a characteristic isotropic EPR
      signal at g= 2.11 were formed. These results are discussed in terms of parallel
      reaction channels that are activated under various conditions of temperature and
      dioxygen.

PMID- 15483711
TI  - Pyrrolyl substituted allenylidene complexes of ruthenium.
AB  - Pyrrolyl and indolyl substituted allenylidene complexes of ruthenium have been
      prepared from the trapping of cationic trans-[Cl(dppm)(2)Ru=C=C=C=CH(2)](+) with
      various pyrroles or N-methylindole. The reaction is rationalized as involving
      regioselective attack of the organometallic electrophile on the electron-rich
      heterocycle followed by proton migration to the terminal =CH(2) entity of the
      intermediate butenynyl substituted sigma-complex. Pyrrolyl substituted
      allenylidene complexes have spectroscopic and electrochemical properties
      intermediate between those of amino and aryl substituted congeners and can thus
      be regarded as vinylogous aminoallenylidene complexes. We present spectroscopic
      evidence that the pyrrole pi-system is efficiently incorporated into the
      metallabutatriene chromophore including resonance Raman spectroscopy. According
      to our results, the respective frontier orbitals are delocalized across the
      entire ClRuC(3)(pyrrolyl) entity which defies any classification of the
      individual redox events as metal or ligand centered redox processes. This issue
      has been specifically addressed by spectroelectrochemistry. The structure of the
      1-methylindole-3-yl complex has been determined by X-ray crystallography. Bond
      parameters along the ruthenium-allenylidene chain are intermediate between those
      of amino and aryl substituted congeners and support our conclusions drawn from
      the spectroscopic results. While still electron rich, pyrrolyl substituted
      allenylidene complexes are easily deprotonated to their conjugate bases, which
      are substituted butenynyl complexes. This has been exemplified with the
      tetrahydroindole derived complex 3f.

PMID- 15483712
TI  - Electro- and photochemical properties of a (mu-alkoxo)bis(mu
      carboxylato)diruthenium complex having two tetraphenylporphinato zinc(II)
      moieties.
AB  - The novel (mu-alkoxo)bis(mu-carboxylato)diruthenium complex K[Ru(2)(dhpta)(mu
      O(2)C-p-ZnTPP)(2)] 3 was prepared by simple ligand substitution reaction. Strong
      antiferromagnetic interaction between two Ru(III) ions of 3 was observed with a
      coupling constant of -425 approximately -404 cm(-1). The cyclic voltammogram of 3
      can be explained in terms of superposition of those of ZnTPP-p-CO(2)H and
      K[Ru(2)(dhpta)(mu-O(2)CPh)(2)] 2, indicating no significant electrochemical
      interaction. The large conproportionation constant estimated from the reduction
      potentials for Ru(III)Ru(III) and Ru(II)Ru(III) indicates great stability of the
      mixed-valence state. The mixed-valence species [Ru(II)Ru(III)(dhpta)(mu-O(2)C-p
      ZnTPP)(2)](2-) 4 was prepared by controlled potential electrolysis. The
      electronic absorption spectrum of 4 was quite similar to that of
      [Ru(II)Ru(III)(dhpta)(mu-O(2)CCH(3))(2)](2-) which is a typical Class II complex.
      The fluorescence from the S(2) state of the ZnTPP unit of 3 was significantly
      (78%) quenched. The electron transfer from the ZnTPP unit to Ru(III) ions in 3 is
      a plausible mechanism, even though energy transfer could not be ruled out
      completely. The free energy change for electron transfer, Delta G(CS), was
      estimated to be ca.-1.1 eV, which is similar to typical values for the
      reorganization energy lambda in polar solvents. Hence, the electron transfer
      scheme is situated almost at the top of the Marcus parabola, enabling ultrafast
      electron transfer.

PMID- 15483713
TI  - Reaction of the silylene Si[(NCH2But)2C6H4-1,2] with the alkali metal silylamides
      M[N(SiMe3)R](M = Li, Na or K; R = SiMe3 or SiMe2Ph).
AB  - The thermally stable silylene Si[(NCH(2)Bu(t))(2)C(6)H(4)-1,2] 1 undergoes
      oxidative addition reactions with the alkali metal silylamides MN(SiMe(3))(2)(M =
      Li, Na or K) to afford the new alkali metal amides MN(SiMe(3))[(1)SiMe(3)][M = Li
      (2), Na (3) or K (4)]. Reaction of two equivalents of 1 with LiN(R)(SiMe(3))
      leads in a two-step process to the compound LiN[(1)R][(1)SiMe(3)][R = SiMe(2)Ph
      (5) or SiMe(3) (6)]. Alternatively, 1 reacts with 3 to afford NaN[(1)SiMe(3)](2)
      (7). The structures of 2-5 and are presented and the formation of 2-7 is
      discussed.

PMID- 15483714
TI  - Pentaaza macrocyclic ytterbium(III) complex and solvent controlled supramolecular
      self-assembly of its dimeric mu-eta 2:eta 2 peroxo-bridged derivatives.
AB  - The unprecedented template action of ytterbium ion in the synthesis of pentaaza
      macrocyclic Schiff bases is exemplified by isolation and definitive
      identification of the seven-coordinate pentagonal bipyramidal complex with the
      formula of [YbLCl(2)]ClO(4) (1), where L is 2,14-dimethyl-3,6,10,13,19
      pentaazabicyclo[13.3.1]nonadeca-1(19),2,13,15,17-pentaene, providing the first
      example of crystallographically characterized pentaaza macrocyclic ytterbium
      complex. For the first time the spectrum of the (2)F(7/2) --> (2)F(5/2)
      transition has been obtained for a molecular complex of ytterbium with organic
      ligands in which all ligand-field components of the ground and excited state are
      well displayed at room temperature. This complex is capable of forming a dimeric
      peroxo Yb(2)(mu-eta(2):eta(2)-O(2))L(2)(4+) (2) derivative containing the
      biologically significant planar side-on doubly bidentate coordination mode of the
      peroxide. Inclusion of the appropriate solvent molecule into the crystal
      structure generates supramolecular architectures (2a-d) in which the solvent
      controlled self-assembly is observed. Spectral properties of these complexes were
      found to be very important and promising in the area of ytterbium
      physicochemistry.

PMID- 15483715
TI  - Synthesis, properties and structures of eight-coordinate zirconium(IV) and
      hafnium(IV) halide complexes with phosphorus and arsenic ligands.
AB  - Eight-coordinate [MX(4)(L-L)(2)] (M = Zr or Hf; X = Cl or Br; L-L = o
      C(6)H(4)(PMe(2))(2) or o-C(6)H(4)(AsMe(2))(2)) were made by displacement of
      Me(2)S from [MX(4)(Me(2)S)(2)] by three equivalents of L-L in CH(2)Cl(2)
      solution, or from MX(4) and L-L in anhydrous thf solution. The [MI(4)(L-L)(2)]
      were made directly from reaction of MI(4) with the ligand in CH(2)Cl(2) solution.
      The very moisture-sensitive complexes were characterised by IR, UV/Vis, and (1)H
      and (31)P NMR spectroscopy and microanalysis. Crystal structures of [ZrCl(4)[o
      C(6)H(4)(AsMe(2))(2)](2)], [ZrBr(4)[-C(6)H(4)(PMe(2))(2)](2)], [ZrI(4)[o
      C(6)H(4)(AsMe(2))(2)](2)] and [HfI(4)[o-C(6)H(4)(AsMe(2))(2)](2)] all show
      distorted dodecahedral structures. Surprisingly, unlike the corresponding Ti(iv)
      systems, only the eight-coordinate complex was found in each system. In contrast,
      the ligand o-C(6)H(4)(PPh(2))(2) forms only six-coordinate complexes [MX(4)[
      C(6)H(4)(PPh(2))(2)]] which were fully characterised spectroscopically and
      analytically. Surprisingly the tripodal triarsine, MeC(CH(2)AsMe(2))(3), also
      produces eight-coordinate [MX(4)[MeC(CH(2)AsMe(2))(3)](2)] in which the
      triarsines bind as bidentates in a distorted dodecahedral structure. There is no
      evidence for seven-coordination as found in some thioether systems.

PMID- 15483716
TI  - Molecular, supramolecular and solution structures of peroxovanadium complexes
      with ON and O3N donor set ligands: two new types of cationic-anionic
      peroxovanadium(V) peroxovanadates(V).
AB  - The complexes, [VO(O(2))(pa)(2)]ClO(4).3H(2)O (1),
      [VO(O(2))(pa)(2)][VO(O(2))(2)(pa)].3H(2)O (2),
      [VO(O(2))(pa)(2)][VO(O(2))(ada)].2H(2)O (3) and [VO(O(2))(pa)(pca)].H(2)O (4)[pa
      = picolinamide, ada = carbamoylmethyliminodiacetate(2-) and pca = 2
      pyrazinecarboxylate(1-)], were synthesized. 2 and 3 are new types of
      peroxovanadium complexes: monoperoxovanadium diperoxovanadate (2) and
      monoperoxovanadium monoperoxovanadate (3). The complexes were characterized by
      chemical analysis and IR spectroscopy, and 1, 3 and 4 also by X-ray analysis. The
      structure of 1 is disordered, with alternating positions of the oxo and peroxo
      ligands. The peroxo oxygen atoms, O(p), in 1 are involved in weak hydrogen bonds
      with water molecules and close intramolecular C-HO...(p) bonds [d(HO(p))
      approximately 2.0 A]. The supramolecular structure of 1 is formed by a network of
      hydrogen bonds and strong attractive intermolecular pi-pi interactions between
      the pyridine rings. The supramolecular architecture in 4 is constructed by (N,O)
      H...O hydrogen bonds between the neutral complex molecules and water of
      crystallization. The peroxo oxygen atoms in 4 form intramolecular C-H...O(p)
      bonds [d(H...O(p))= 2.303 A]. The pa and pca ligands are ON coordinated via the
      oxygen atoms of the C(NH(2))=O and COO(-) groups, respectively, and nitrogen
      atoms of the heterocyclic rings, and ada as a tetradentate O(3)N ligand. The
      thermal analysis of 4 showed that the loss of water of crystallization and the
      active oxygen release (T(min)/ degrees C 82, T(max)/degrees C 165) are, under
      given conditions, individual processes separated by the temperature interval 90
      132 degrees C. The solution structures and stability were studied by UV-VIS and
      (51)V NMR spectroscopies.

PMID- 15483717
TI  - Sterically hindered electron-withdrawing ligands: the reactions of N-carbazolyl
      phosphines with rhodium and palladium centres.
AB  - The series of N-carbazolyl phosphines PPh(3-n)(NC(12)H(8))(n)(n= 1, L1; n= 2, L2;
      n= 3, L3) has been synthesised using BuLi to generate the N-carbazolyl lithium
      salt, followed by reaction with the appropriate chlorophosphine. The reactions
      between [Rh(mu-Cl)(CO)(2)](2) and four equivalents of L1 or L2 gave
      [RhCl(CO)(L1)(2)] 1 and [RhCl(CO)(L2)(2)] 2, though attempts to synthesise the
      analogous complex using L3 resulted in the formation of [Rh(mu-Cl)(CO)(L3)](2) 3
      instead. The inability of L3 to cleave the chloride bridges can be related to its
      considerable steric requirements. The electronic properties of L1-3 were assessed
      by comparison of the nu(CO) values of the [Rh(acac)(CO)(L1-3)] complexes 4-6. The
      increase in number of N-carbazolyl substituents at the phosphorus atom results in
      a decrease of the sigma-donor and increase in the pi-acceptor character in the
      order L1 < L2 < L3. In the reactions of L1-3 with [PdCl(2)(cod)] only L1 was able
      to displace cod from the metal centre and form [PdCl(2)(L1)(2)] 7. The use of
      [PdCl(2)(NCMe)(2)] instead of [PdCl(2)(cod)] resulted in the formation of the
      complexes [PdCl(2)(L1)(2)] 7 from L1, the cyclometallated complex [Pd(mu
      Cl)[P(NC(12)H(8))(2)(NC(12)H(7))-kappa(2)P,C]](2) 8 from L3 , and a mixture of
      [PdCl(2)(L2)(2)] 9 and [Pd(mu-Cl)[PPh(NC(12)H(8))(NC(12)H(7))-kappa(2)P,C]](2) 10
      from L2 . The reaction of L3 with [Pd(OAc)(2)] produced the cyclometallated
      complex [Pd(mu-O(2)CCH(3))[P(NC(12)H(8))(2)(NC(12)H(7))-kappa(2)P,C]](2) 11. The
      reaction of L3 with [Pd(2)(dba)(3)].CHCl(3) produced the 14-electron complex
      [Pd(L3)(2)] 12. The X-ray crystal structures of six complexes are reported, all
      of which show the presence of C-H...Pd hydrogen bonding.

PMID- 15483718
TI  - Photochemical reactions of (eta 5-cyclopentadienyl)bis(t-butylacrylate) rhodium
      with silanes: dynamics of isomer interconversion via Rh(eta 2-silane) species.
AB  - The compound CpRh(C(2)H(3)CO(2)(t)Bu)(2) 1 has been synthesised as a mixture of
      two pairs of interconverting isomers which differ in the relative orientations of
      the alkene substituents. The four isomers have been fully characterised by NMR
      spectroscopy. When complex 1 is photolysed in the presence of a silane,
      HSiR(2)R'R(2)R'= Et(3), Me(3), HEt(2), (OMe)(3) and Me(2)Cl] the corresponding Si
      H oxidative addition products CpRh(SiR(2)R')(H)(C(2)H(3)CO(2)(t)Bu) and
      CpRh(H)(2)(SiR(2)R')(2) are formed. The Rh(III) complexes
      CpRh(SiR(2)R')(H)(C(2)H(3)CO(2)(t)Bu) exist in two isomeric forms of comparable
      energy which interconvert in an intramolecular process that does not involve a
      reversible [1,3] hydride or [1,3] silyl migration. The hydride (1)H NMR
      resonances for these species consequently broaden before coalescing into a single
      peak. For R(2)R'= Et(3), the activation parameters for interchange from the major
      to minor isomer were Delta H++= 60.2 +/- 2 kJ mol(-1) and Delta S++= 8 +/- 9 J
      mol(-1) K(-1), while for R(2)R'= Me(3) and Et(2)H, Delta H++= 61.5 +/- 1 kJ mol(
      1), Delta S++= 6 +/- 5 J mol(-1) K(-1), and Delta H++= 61.8 +/- 3 kJ mol(-1),
      Delta S++= 12 +/- 9 J mol(-1) K(-1) respectively for conversion from the major
      isomer to the minor. For these complexes an eta(2)-Rh-H-Si transition state or
      intermediate is consistent with the evidence. When R(2)R'=(OMe)(3) and Me(2)Cl
      the change in appearance of the hydride resonances is more complex, with the
      activation parameters for interchange from the major to minor isomer for the
      former species being Delta H++= 78.3 +/- 2 kJ mol(-1) and Delta S++= 30 +/- 7 J
      mol(-1) K(-1) while for Me(2)Cl the barrier proved too high to measure before
      decomposition occurred. The complex spectral changes could be simulated when a
      discrete eta(2)-Rh-H-Si intermediate was involved in the isomer interconversion
      process and hence silane rotation in all these systems is proposed to involve two
      isomers of CpRh(eta(2)-HSiR(2)R')(C(2)H(3)CO(2)(t)Bu).

PMID- 15483719
TI  - Heterogenisation of CpMo(CO)3Cl on mesoporous materials and its application as
      olefin epoxidation catalyst.
AB  - CpMo(CO)(3)Cl reacts with the hydroxyl (Si-OH or Si-OH-Al) functionalities of
      mesoporous molecular sieves such as MCM-41, MCM-48 and its aluminium analogues
      during grafting. XRD, N(2) adsorption-desorption, BET surface area analysis and
      TEM show the resulting samples as being well ordered and maintaining a uniform
      pore size. FT-IR spectra, elemental analysis, (13)C and (29)Si CP MAS NMR spectra
      confirm the successful grafting. In the presence of excess TBHP the materials
      show high activity in cyclooctene epoxidation and good stability.

PMID- 15483720
TI  - Iron catalysed assembly of an asymmetric mixed-ligand triple helicate.
AB  - The 2-pyridinecarbaldehyde isonicotinoyl hydrazone (HPCIH) family of ligands are
      typically tridentate N,N,O chelators that exhibit very high in vitro activity in
      mobilizing intracellular Fe and are promising candidates for the treatment of Fe
      overload diseases. Complexation of ferrous perchlorate with HPCIH in MeCN
      solution gives the expected six-coordinate complex Fe(II)(PCIH)(2). However,
      complexation of Fe(II) with 2-pyridinecarbaldehyde picolinoyl hydrazone (HPCPH,
      an isomer of HPCIH) under the same conditions leads to spontaneous assembly of an
      unprecedented asymmetric, mixed-ligand dinuclear triple helical complex
      Fe(II)(2)(PCPH)(2)(PPH), where PPH(2-) is the dianion of
      bis(picolinoyl)hydrazine. The X-ray crystal structure of this complex shows that
      each ligand binds simultaneously to both metal centres in a bidentate fashion.
      The dinuclear complex exhibits two well separated and totally reversible
      Fe(III/II) redox couples as shown by cyclic voltammetry in MeCN solution.

PMID- 15483721
TI  - The preparation and characterisation of bimetallic iridium(II) complexes
      containing derivatised bridging naphthalene-1,8-disulfur or 4,5-dithiolato
      acephenanthrylene ligands.
AB  - Oxidative addition of the disulfide compounds naphtho[1,8-cd][1,2]dithiole, 2
      tert-butylnaptho[1,8-cd][1,2]dithiole, 2,7-di-tert-butylnaphtho[1,8
      cd][1,2]dithiole, 4,5-dithiaacephenanthrylene and the thio/sulfinyl and
      thio/sulfonyl compounds naphtho[1,8-cd][1,2]dithiole 1-oxide, and naphtho[1,8
      cd][1,2]dithiole 1,1-dioxide respectively to [[Ir(mu-Cl)(cod)](2)] give dinuclear
      Ir-Ir bonded Ir(II) compounds [[IrCl(cod)](2)(mu(2)-1,8-S(2)-nap)] 1,
      [[IrCl(cod)](2)(mu(2)-1,8-S(2)-2-(t)Bu-nap)] 2, [[IrCl(cod)](2)(mu(2)-1,8-S(2)
      2,7-di-(t)Bu-nap)]] 3, [[IrCl(cod)](2)(mu(2)-4,5-S(2)-phenan)] 4,
      [[IrCl(cod)](2)(mu(2)-1-S,8-[S(O)]-nap)] 5 and [[IrCl(cod)](2)(mu(2)-1-S,8
      [S(O)(2)]-nap)] 6 where the di-sulfur ligands act as bridges between the two
      Ir(II) metal centres. The compounds were obtained in moderate to good yields as
      orange or deep red powders or crystalline solids. Five of the new complexes have
      been structurally characterised and were found to have Ir-Ir bond lengths in the
      range 2.7630(8) to 2.8113(11) A.

PMID- 15483722
TI  - M...HNR interactions in imino-bound diaryltriazene complexes: structure and
      fluxionality.
AB  - The nominally square-planar coordination of the d(8) complexes [MClL(1)L(2)(p
      XC(6)H(4)NNNHC(6)H(4)X-p)](M = Rh, L(1)= L(2)= CO, X = H, Me, Et or F; M = Ir,
      L(1)= L(2)= CO, X = Me; M = Pd or Pt, L(1)= Cl, L(2)= PPh(3), X = Me; M = Pd,
      L(1)L(2)=eta(3)-C(3)H(5), X = Me), with the triazene N-bonded via the imine
      group, is supplemented by an axial M...H-N interaction involving the terminal
      amino group.

PMID- 15483723
TI  - Azido- or hydroxyl-capped half-cubanes containing Cp*Rh fragments: [Cp*3Rh3(mu
      X)3(mu3-X)]2+ (X-=OH- or N3-).
AB  - Treatment of [Cp*Rh(H(2)O)(3)](OTf)(2) (1) with Me(3)SiNH-t-Bu in acetone gave a
      hydroxyl-capped half-cubane [Cp*(3)Rh(3)(mu-OH)(3)(mu(3)-OH)](OTf)(3)(t-BuNH(3))
      (2). Slow diffusion of Me(3)SiN(3) in diethyl ether into compound in acetone
      produced an azido-capped half-cubane [Cp*(3)Rh(3)(mu-N(3))(3)(mu(3)
      N(3))](OTf)(2) (3). On the other hand, treating 1 with Me(3)SiN(3) in acetone
      gave an azido-bridged, dinuclear rhodium(III) complex [Cp*Rh(mu
      N(3))(OH(2))](2)(OTf)(2) (4). Complexes 2 and 3 represent the first azido- or
      hydroxyl-capped, incomplete cubane-type Rh clusters. Under appropriate
      conditions, complexes 2 and 3 could be converted to complex 4. The structures of
      all products were determined by X-ray diffraction.

PMID- 15483724
TI  - Metal-oxygen-metal arrays in lamellar hybrid materials: cobalt and manganese 4
      cyclohexene-1,2-dicarboxylates.
AB  - We have obtained three layered hybrid materials from the hydrothermal reaction of
      4-cyclohexene-1,2-dicarboxylic acid with Co and Mn salts: Co(C(8)H(8)O(4))[1],
      Mn(H(2)O)(C(8)H(8)O(4))[2], and Mn(4)(H(2)O)(C(8)H(8)O(4))(4).0.3(H(2)O)[3]. The
      structures for all materials were solved by single-crystal XRD ([1]P1, a=4.805(2)
      A, b=6.650(3) A, c=12.960(6) A, alpha=98.285(7) degrees, beta=98.986(7) degrees,
      gamma=95.689(7) degrees, V= 401.6(3) A(3), R(1)= 0.0438; [2] P2(1)/c, a=11.151(2)
      A, b=11.330(2) A, c=7.6560(15) A, beta=108.813(3) degrees , V=915.6(3) A(3),
      R(1)=0.0412; [3] P1, a= 11.412(3) A, b=12.136(4) A, c=13.809(4) A,
      alpha=104.703(6) degrees, beta=103.207(6) degrees, gamma=92.468(5) degrees,
      V=1790.6(9) A(3), R(1)=0.1056). While all three structures are two-dimensional
      overall, the metal-oxygen-metal dimensionality within the layers varies from
      isolated metal atoms in the case of [1] to 1D ribbons of vertex sharing MnO(6)
      octahedra [2] and 2D arrays of edge- and vertex-sharing polyhedra in [3].

PMID- 15483725
TI  - Designing dinuclear iron(II) spin crossover complexes. Structure and magnetism of
      dinitrile-, dicyanamido-, tricyanomethanide-, bipyrimidine- and tetrazine-bridged
      compounds.
AB  - In order to expand the few known examples of dinuclear iron(II) compounds
      displaying (weak) intradinuclear exchange coupling and spin-crossover on one or
      both of the iron(II) centres, various dinuclear compounds have been synthesised
      and assessed for their spin-crossover and exchange coupling behaviour. The key
      aim of the work was to prepare and structurally characterise 'weakly linked' and
      'covalently bridged' systems incorporating bridging ligands such as
      alkyldinitriles (e.g.NC(CH(2))(4)CN), bipyrimidine (bpym), dicyanamide (dca(-)),
      tricyanomethanide (tcm(-)), 3,6-bis(2-pyridyl)tetrazine (bptz) and 3,6-bis(2
      pyridyl)2,5-dihydrotetrazine (H(2)bptz). The 'end groups', which complete the
      Fe(ii)N(6) chromophores, include tris(2-pyridylmethyl)amine (tpa), di(2
      pyridylethyl)(2-pyridylmethyl)amine (tpa'), 3-(2-pyridyl)pyrazole (pypzH), 1,10
      phenanthroline (1,10-phen), tris(pyrazolyl)methane (tpm) and NCX(-)(X = S, Se).
      It was quite difficult to achieve the spin-crossover condition, many ligand
      combinations yielding high-spin/high-spin (HS-HS) Fe(II)Fe(II) spin states at all
      temperatures (300-2 K) with very weak antiferromagnetic coupling (J < -1 cm(-1)),
      two such being the crystallographically characterised [(dca)(tpm)Fe(mu(1,5)
      dca)(2)Fe(tpm)(dca)], 5, and [(tpa')Fe(mu(1,5)
      tcm)(2)Fe(tpa')](tcm)(2)(H(2)O)(2), 6. In contrast, a strong field was created
      around the Fe(II) centres in [(tpa)Fe(mu
      (NC(CH(2))(4)CN))(2)Fe(tpa)](ClO(4))(4).NC(CH(2))(4)CN, 1, and the Fe-N bond
      distances, at 173 K, reflected this. This weakly-linked dinitrile example showed
      a spin-crossover beginning above 300 K. 'Half crossover' examples, yielding HS-LS
      states below the spin transition, similar to those noted by Real and coworkers in
      some mu-bpym systems, were noted for [(1,10-phen)(NCS)(2)Fe(mu
      bpym)Fe(NCS)(2)(1,10-phen)], 2, [(pypzH)(NCSe)(2)Fe(mu-bpym)Fe(NCSe)(2)(pypzH)],
      4, and [(tpa)Fe(mu-H(2)bptz)Fe(tpa)](ClO(4))(4), 8. Interestingly, the mu-bptz
      analogue, 7, remained LS-LS at all temperatures with the start of a broad spin
      crossover evident above 300 K. No thermal hysteresis was evident in the spin
      transitions of these new dinuclear crossover species indicating a lack of intra-
      or interdinuclear cooperativity.

PMID- 15483726
TI  - Synthesis of mixed Ar,Ar'-BIAN ligands (Ar,Ar'-BIAN =
      bis(aryl)acenaphthenequinonediimine). Measurement of the coordination strength of
      hemilabile ligands with respect to their symmetric counterparts.
AB  - The synthesis of Ar,Ar'-BIAN ligands (Ar,Ar'-BIAN =
      bis(aryl)acenaphthenequinonediimine) having different aryl groups bound to the
      two nitrogen atoms is reported for the first time. The ligands were obtained by
      two different strategies: (i) by a transimination reaction starting from a
      symmetric Ar,Ar-BIAN ligand having aryl groups bearing strongly electron
      withdrawing substituents or (ii) by a two-step-one-pot sequence. The ligands
      synthesized have been chosen so that the electronic difference between the two
      aryl groups is very large, but the steric difference is variable and, in one
      case, the ligand is almost sterically symmetric. The coordination strength of the
      new ligands towards three palladium complexes has been measured by a competition
      experiment following a protocol previously described by us. The coordination
      strength of the mixed ligands is the mean of those of the corresponding symmetric
      counterparts. The X-ray crystal structure of a palladium pi-allyl complex of the
      electronically asymmetric-sterically symmetric ligand (3,5
      (CF(3))(2)C(6)H(3)),(3,5-Me(2)C(6)H(3))-BIAN has been solved, together with those
      of the two symmetric analogues to allow a comparison. Despite the fact that the
      dodecafluorinated ligand has a K(eq) value about three orders of magnitude lower
      than the non-fluorinated counterpart, no notable difference is observed in the N
      Pd and Pd-C(allyl) distances in the three complexes. Calculations at the density
      functional level confirm that Pd-BIAN distances are not strictly correlated to
      the coordination energies, which are in qualitative agreement with the
      spectroscopic evidence. The bond length is thus not a good indication of the bond
      strength in these cases.

PMID- 15483727
TI  - Reactions of 2-indolylphosphines with Ru3(CO)12: cluster capping with mu 3,eta 2
      indolylphosphine as an anionic six-electron P,N-donor ligand.
AB  - Stepwise bidentate coordination of the novel indolylphosphine ligands HL (1, HL =
      P(C(6)H(5))(2)(C(9)H(8)N)(diphenyl-2-(3-methylindolyl)phosphine); 2, HL =
      P(C(6)H(5))(C(9)H(8)N)(2)(phenyldi-2-(3-methylindolyl)phosphine); and 3, HL =
      P(C(6)H(5))(C(17)H(12)N(2))(di(1H-3-indolyl)methane-(2,12)-phenylphosphine)) to
      the ruthenium cluster Ru(3)(CO)(12) is demonstrated. Reactions of 1-3 with
      Ru(3)(CO)(12) led to the formation of Ru(3)(CO)(11)(HL) (4-6), in which HL is
      mono-coordinated through the phosphorus atom. The X-ray structures of 4-6 show
      that the phosphorus atom is equatorially coordinated to the triruthenium core. In
      all cases, gentle heating of Ru(3)(CO)(11)(HL) resulted in the formation of
      Ru(3)(CO)(9)(mu-H)(mu(3),eta(2)-L)(7-9) in which the NH proton of the indolyl
      substituent had migrated to the ruthenium core to form a bridging hydride ligand.
      The X-ray structure of Ru(3)(CO)(9)(mu-H)[mu(3),eta(2)-P(C(6)H(5))(2)(C(9)H(7)N)]
      (7) shows the deprotonated nitrogen atom of the indolyl moiety bridging over the
      face of the triruthenium core, bonding to the two ruthenium metal centers to
      which the phosphorus atom is not bound. The phosphorus atom is forced to adopt an
      axial bonding mode due to the geometry of the indolylphosphine ligand. Cluster
      electron counting and X-ray data suggest that the indolylphosphine behaves as a
      six-electron ligand in this mode of coordination. Compounds 4-9 have been
      characterized by IR, (1)H, (13)C and (31)P NMR spectroscopy.

PMID- 15483728
TI  - Constructing homo- and hetero-metallic molecular topologies using
      pyridylcarboxylates as spacers: preparation of a half-ring complex with active
      coordination sites.
AB  - Addition of isonicotinic acid NC(5)H(4)CO(2)H (or isonicH) to
      [Pt(dppf)(MeCN)(2)](2+)2OTf(-)(dppf = 1,1'-bis(diphenylphosphino)ferrocene, OTf =
      triflate) affords a mixture of the homometallic molecular square
      [Pt(4)(dppf)(4)(mu-O(2)CC(5)H(4)N)(4)](4+)4OTf(-), 1 and its precursor
      intermediate [Pt(dppf)(eta(1)-NC(5)H(4)CO(2)H)(2)](2+)2OTf(-), 2. The latter
      captures [Pd(dppf)(MeCN)(2)](2+)2OTf(-) to give a heterometallic square,
      [Pt(2)Pd(2)(dppf)(4)(mu-O(2)CC(5)H(4)N)(4)](4+)4OTf(-), 3. Slight skeletal
      modification of the ligand leads to different assemblies. This is illustrated by
      the addition of NC(5)H(4)CH(2)CO(2)H.HCl to [Pt(dppf)(MeCN)(2)](2+)2OTf(-) to
      give [PtCl(dppf)(NC(5)H(4)CH(2)CO(2)H)](+)OTf(-), 4, which reacts with another
      equivalent of AgOTf to yield the dibridged complex [Pt(2)(dppf)(2)(mu
      NC(5)H(4)CH(2)CO(2))(2)](2+)2OTf(-), 5. All complexes, with the exception of ,
      have been structurally characterized by single-crystal X-ray crystallography.
      Complexes 2 and 4 are potential precursors to further molecular topologies.

PMID- 15483729
TI  - Aggregation control by homologous tripodal tetradentate amino acid ligands in oxo
      bridged diiron(III) aquo complexes.
AB  - Isoelectronic oxo-bridged diiron(III) aquo complexes of the homologous tripodal
      tetradentate amino acid ligands, N,N'-bis(2-pyridylmethyl)-3-aminoacetate (bpg(
      )) and N,N'-bis(2-pyridylmethyl)-3-aminopropionate (bpp(-)), containing
      [(H(2)O)Fe(III)-(mu-O)-Fe(III)(H(2)O)](4+) cores, oligomerise, respectively, by
      dehydration and deprotonation, or by dehydration only, in reversible reactions.
      In the solid state, [Fe(2)(O)(bpp)(2)(H(2)O)(2)](ClO(4))(2) (1(ClO(4))(2))
      exhibits stereochemistry identical to that of
      [Fe(2)(O)(bpg)(2)(H(2)O)(2)](ClO(4))(2) (2(ClO(4))(2)), with the ligand
      carboxylate donor oxygen atoms and the water molecules located cis to the oxo
      bridge and the tertiary amine group trans to it. Despite their structural
      similarity, 1(2+) and 2(2+) display markedly different aggregation behaviour in
      solution. In the absence of significant water, 1(2+) dehydrates and dimerises to
      give the tetranuclear complex, [Fe(4)(O)(2)(bpp)(4)](ClO(4))(4) (3(ClO(4))(4)),
      in which the carboxylate groups of the four bpp(-) ligands act as bridging groups
      between two [Fe(2)(O)(bpp)(2)](2+) units. Under similar conditions, 2(2+)
      dehydrates and deprotonates to form dinuclear and trinuclear oligomers,
      [Fe(2)(O)(OH)(bpg)(2)](ClO(4)) (4ClO(4)) and [Fe(3)(O)(2)(OH)(bpg)(3)](ClO(4))
      (5(ClO(4))), related by addition of 'Fe(O)(bpg)' units. The trinuclear 5(ClO(4)),
      characterised crystallographically as two solvates 5(ClO(4)).3H(2)O and
      5(ClO(4)).2MeOH, is based on a hexagonal [Fe(3)(O)(2)(OH)(bpg)(3)](+) unit,
      formally containing one hydroxo and two oxo bridges. The different aggregation
      behaviour of 1(ClO(4))(2) and 2(ClO(4))(2) results from the difference of one
      methylene group in the pendant carboxylate arms of the amino acid ligands.

PMID- 15483730
TI  - Stoichiometric reactions of methylparathion with a palladium aryl oxime
      metallacycle.
AB  - The reaction of [Pd(3)(OAc)(6)] with (E)-acetophenone oxime and pyridine in
      CHCl(3) under reflux affords the metallacycle [Pd(OAc)[C,N-(C(6)H(4)C(CH(3))=NOH)
      2](py)] (1) as a yellow air-stable complex. The same reaction carried out at room
      temperature in the absence of pyridine affords the trinuclear oximato complex
      [Pd(mu-(E)-ON=C(CH(3))Ph)(mu-OAc)](3) (2), which can be converted into 1 upon
      heating in the presence of pyridine. As indicated by (1)H and (31)P NMR
      spectroscopy, complex 1 reacts with methylparathion in acetone-d(6)-D(2)O
      solutions to afford [Pd(SP(=O)(OCH(3))(2))[C,N-(C(6)H(4)C(CH(3))=NOH)-2](py)] (3)
      and [Pd(mu-SP(=O)(OCH(3))(2))[C,N-(C(6)H(4)C(CH(3))=NOH)-2]](2) (4) as well as
      free p-nitrophenol. Compounds 1-4 have been characterized by single-crystal X-ray
      analysis, NMR and EA. Compounds 1 and 3 are mononuclear complexes with the
      acetate and dimethylthiophosphate ligand, respectively, trans from the phenyl
      group. Compound 2 is a trinuclear complex whose structure can be derived from
      that of [Pd(3)(OAc)(6)] by replacing three of the acetate ligands on one side of
      Pd(3) plane by three N,O-coordinated oximate ligands. Complex 4 is a dinuclear
      complex in which the two square-planar palladium moieties are linked by the
      sulfur atoms of the bridging dimethylthiophosphate ligands.

PMID- 15483731
TI  - Cellular injury in ischaemia.

PMID- 15483732
TI  - Hyperhomocyst(e)inemia is an important risk factor for vascular disease in
      subjects with high-molecular weight apo(a) isoforms.
AB  - BACKGROUND: Homocyst(e)ine is reported to increase the binding of lipoprotein(a)
      [Lp(a)] to fibrin, which may increase the thrombogenic effects of Lp(a) in vivo.
      The aim of this study was to investigate whether there is a relationship between
      homocyst(e)ine and Lp(a) levels and vascular disease risk, and if the
      relationship depends on the apo(a) isoforms. METHODS: A case-control study was
      performed in 91 Caucasian male subjects with vascular disease due to
      athersclerosis, and in 100 healthy age- and sex-matched control subjects.
      RESULTS: Both hyperhomocyst(e)inemia and elevated Lp(a) were significantly more
      prevalent in patients. Concordant elevated Lp(a) and hyperhomocyst(e)inemia were
      not associated with increased vascular disease risk (relative odds 2.96; 95% CI:
      0.90-9.80), while hyperhomocyst(e)inemia in the absence of elevated Lp(a) was
      associated with increased vascular disease risk (relative odds 7.20; 95% CI: 2.37
      21.91). Hyperhomocyst(e)inemia in individuals with high-molecular weight apo(a)
      isoforms [smaller apo(a) isoform > S3] was observed to be associated with
      increased vascular disease risk (relative odds 11.02; 95% CI: 3.54-34.30), while
      vascular disease risk in subjects with low-molecular weight apo(a) isoforms
      [smaller apo(a) isoform < S3] was not significantly increased, the relative odds
      being 1.92; 95% CI: 0.51-7.24. CONCLUSIONS: We conclude that
      hyperhomocyst(e)inemia is an important risk factor in individuals with high
      molecular weight apo(a) isoforms.

PMID- 15483733
TI  - Risk factors and complications of hypertension in Yaounde, Cameroon.
AB  - AIM: To determine the risk factors and complications of hypertension, isolated
      systolic hypertension (ISH) and isolated diastolic hypertension (IDH) in Yaounde.
      METHODS AND RESULTS: Between January and September 1998 we examined 813
      consecutive adult patients (46.5% men) in the Yaounde University Teaching
      Hospital, with special focus on risk factors of hypertension and clinical
      findings in the cardiovascular system. We measured systolic blood pressure,
      diastolic blood pressure, body mass index and plasma glucose, and recorded chest
      X-ray, electrocardiogram and echocardiogram. Hypertension, ISH and IDH were
      defined using the WHO-ISH 1999 criteria. After controlling for the confounding
      effects of age and sex, hypertension was significantly associated with obesity,
      family history of hypertension, alcohol intake, heart failure, stroke and left
      ventricular hypertrophy (p < 0.01); smoking was significantly associated with ISH
      (p = 0.04), and no factor was independently associated with IDH. CONCLUSIONS: A
      prevention strategy for hypertension and its resultant complications in Cameroon
      should include measures aimed at obesity and alcohol consumption, as well as
      early diagnosis with the institution of effective and affordable therapy.

PMID- 15483735
TI  - SA Heart Association National Congress, 6-8 October 2004, Durban, South Africa.
      Abstracts.

PMID- 15483736
TI  - New pathophysiological insights explain life-saving benefits of perindopril in
      coronary artery disease patients.

PMID- 15483737
TI  - ACTION with nifedipine GITS (Adalat XL) provides evidence for safety and improved
      outcome in angina patients.

PMID- 15483738
TI  - CHARM study in CHF patients with impaired LV function reinforces benefits of
      candesartan cilexetil (Atacand).

PMID- 15483739
TI  - Fixed-combination therapy for hypertension increases success rate.

PMID- 15483740
TI  - Teveten (eprosartan) reduces future risk in hypertensive stroke patients.

PMID- 15483741
TI  - Significant reduction in heart attacks in patients taking Pfizer's Lipitor.

PMID- 15483743
TI  - Immunosuppression in human peripheral blood T lymphocytes by fluvastatin.
AB  - To investigate the immunosuppressive effect of fluvastatin on the PHA-activated T
      lymphocytes. T lymphocytes were isolated from the blood of healthy volunteers,
      cell proliferation and the activation markers expression were examined by flow
      cytometric analysis. Cytokine secretion was assayed by ELISA. LDH-release assay
      was used to detect activity of killer cells. NFAT activation was evaluated by
      TransAM ELISA kit. Results were as following. (1) Whereas no modification in CD25
      expression was seen, fluvastatin at 5 microM caused a lower level of CD69
      expression, accompanied by an essential suppression on proliferation, IL-2
      production and cytotoxicity development in PHA-stimulated T cells. However, the
      level of secreted IL-10 had no change, and the level of IL-4 even experienced a
      significant increase. (2) Combined with cyclosporine A (CsA), fluvastatin would
      further repress CD69 expression, cells proliferation and activity of killer
      cells, meanwhile significantly induced the secretion of IL-4 and IL-10. (3)
      Fluvastatin treatment also resulted in a strong inhibition of NFAT activation. In
      conclusion, partly involving the blockage of activation of NFAT, fluvastatin
      exhibited an immunosuppressive effect in vitro.

PMID- 15483744
TI  - The cDNA and genomic DNA organization of a novel toxin SHT-I from spider
      Ornithoctonus huwena.
AB  - In present study the full-length cDNA of a novel toxin from the venom gland of
      spider Ornithoctonus huwena, named as SHT-I, has been cloned using the strategy
      of rapid amplification of cDNA ends, and then the whole genomic sequence of SHT-I
      (Selenocosmia huwena toxin-I) was determined using sequence-specific primers
      synthesized based on the acquired 3' and 5' ends of SHT-I cDNA sequence. It is
      unexpectedly found that intron was lacking in the genomic sequence of SHT-I. The
      result might evoke an interesting question whether the gene code of inhibitor
      cystine-knot peptides from spider venom is distinct from that of those known
      toxic peptides of scorpion and cone snail.

PMID- 15483745
TI  - NO level and endothelial NO synthase gene polymorphism (Glu298Asp) in the
      patients with coronary artery disease from the Turkish population.
AB  - Nitric oxide is synthesized from L-arginine by endothelial nitric oxide synthase
      encoded by eNOS gene. This study was performed to investigate the relationship
      between the serum nitric oxide level and eNOS gene polymorphism in the Turkish
      population with angiographically diagnosed coronary artery disease (63.47 +/-
      9.10 years old, n=250) and control subjects without any history and/or risk
      factors of coronary artery disease (60.71 +/- 9.14 years old, n=150). Griess
      assay and PCR-RFLP analysis were used to measure the serum nitric oxide
      metabolites and genotypes, respectively. It was found that Glu/Glu, Glu/Asp and
      Asp/Asp genotype frequencies of the eNOS were 49.3%, 41.3% and 9.3% respectively
      in the control group, and 45.6%, 41.2% and 13.2% in the patient group. Serum
      nitric oxide levels were (32.56 +/- 17.26) microM in controls and (29.84 +/-
      11.88) microM in patients. Neither the frequencies of the Glu298Asp genotypes nor
      the serum nitricoxide levels showed a significant difference between the groups.
      There was also no correlation between serum nitric oxide levels and the
      frequencies of the eNOS genotypes. Result showed that the coronary artery disease
      of the Turkish population seemed to develop without any alterations in eNOS
      Glu298Asp genotype frequency and the serum nitric oxide level.

PMID- 15483746
TI  - Novel cellulase profile of Trichoderma reesei strains constructed by cbh1 gene
      replacement with eg3 gene expression cassette.
AB  - To construct strains of the filamentous fungus Trichoderma reesei with low
      cellobiohydrolases while high endoglucanase activity, the P(cbh1)-eg3-T(cbh1)
      cassette was constructed and the coding sequence of the cellobiohydrolase I
      (CBHI) gene was replaced with the coding sequence of the eg3 gene by homologous
      recombination. Disruption of the cbh1 gene was confirmed by PCR, Southern dot
      blot and Western hybridization analysis in two transformants denoted as L13 and
      L29. The filter paper-hydrolyzing activity of strain L29 was 60% of the parent
      strain Rut C30, and the CMCase activity was increased by 33%. This relatively
      modest increase suggested that the eg3 cDNA under the control of the cbh1
      promoter was not efficiently transcribed as the wild type cbhl gene. However our
      results confirmed that homologous recombination could be used to construct
      strains of the filamentous fungus Trichoderma reesei with novel cellulase
      profile. Such strains are of interest from the basic science perspective and also
      have potential in ustrial applications.

PMID- 15483747
TI  - Functional analysis of multiple transcription factor sites in a regulatory
      element of human epsilon-globin gene.
AB  - The developmental control of the human epsilon-globin gene expression is mediated
      by transcriptional regulatory elements in the 5' flanking DNA of this gene. A
      previously identified negative regulatory element (-3028 to -2902 bp, termed
      epsilon-NRAII) was analyzed and one putative NF-kappaB site and two GATA sites
      locate at -3004 bp, -2975 bp and -2948 bp were characterized. Electrophoresis
      mobility shift assay (EMSA) showed that the putative NF-kappaB site was
      specifically bound by nuclear proteins of K562 cells. Data obtained from
      transient transfection showed that the expression of reporter gene could be
      upregulated about 50% or 100% respectively when epsilon-NRAII was inserted
      upstream of the SV40 promoter or epsilon-globin gene proximal promoter (-177 bp
      to +1 bp), suggesting that epsilon-NRAII might not be a classic silencer.
      Mutation in the putative NF-kappaB site or in the GATA site (at -2975 bp)
      slightly reduced the expression of reporter gene driven by SV40 promoter or
      epsilon-globin gene proximal promoter. However, the mutation of GATA site at 
      2948 bp remarkably reduced the reporter gene activity driven by SV40 promoter,
      but not by epsilon-globin gene proximal promoter. Further mutation analysis
      showed that the negative effect of mutation in GATA site at -2948 bp on SV40
      promoter was not affected by the mutation of the putative NF-kappaB site, whereas
      it could be abolished by the mutation of GATA site at -2975 bp. Furthermore, the
      mutation of both GATA sites could synergistically reduce the reporter gene
      activity driven by epsilon-globin gene proximal promoter. Those results suggested
      that epsilon-NRAII might function differently on the SV40 promoter and epsilon
      globin gene proximal promoter.

PMID- 15483748
TI  - Detection of tumor marker CA125 in ovarian carcinoma using quantum dots.
AB  - Semiconductor quantum dots (QDs) offer several advantages over organic dyes in
      fluorescence-imaging applications, such as higher quantum yield, exceptional
      photostability, and a narrow, tunable, and symmetric emission spectrum. To
      explore whether QDs could specifically and effectively label tumor markers and be
      used in immunohistochemistry as a novel type of fluorescent probe, we used
      quantum dots with maximum emission wavelength 605 nm (QD605) to detect the
      ovarian carcinoma marker CA125 in specimens of different types (fixed cells,
      tissue sections, and xenograft piece). Additionally, we compared the
      photostability of QD signals with that of a conventional organic dye, FITC. All
      labeling signals of QDs were found to be more specific and brighter than those of
      FITC. Moreover, the QDs exhibited exceptional photostability during continuous
      illumination for 1 h by a high-intensity laser (Ar laser power 100 mW) at 488 nm,
      while the FITC signals faded very quickly and became undetectable after 24 min of
      illumination. These results indicate that QD-based probes can offer substantial
      advantages over existing fluorophores in many applications, and can be used
      effectively in immunohistochemistry as a novel class of fluorescent probes.

PMID- 15483749
TI  - Temporal and tight hepatitis C virus gene activation in cultured human hepatoma
      cells mediated by a cell-permeable Cre recombinase.
AB  - Conditional gene expression has greatly facilitated the examination of the
      functions of particular gene products. Using the Cre/lox P switching expression
      system, we plan to develop efficient conditional transgene activation of
      hepatitis C virus core protein (HCV-C) cDNA (nucleotide 342-914) in the
      transgenic mice to overcome "immune tolerance" formed during the embryonic period
      and "immune escape" against hepatitis virus antigen in our project. To use this
      system in vivo, the dormant transgenic construct, i.e., pApoE-SCS-EGFP-HCV-C, was
      generated using techniques of standard molecular biology. The liverspecific human
      apoE promoter was here used to target expression of genes of interest (EGFP and
      HCV-C) to murine liver. Prior to generating the transgenic mice, the availability
      of Cre/lox P system and construct functionality were successfully verified by a
      cell-free recombination system and via checking the expression of EGFP and HCV-C
      in the human hepatoma cells at the mRNA and protein levels. These results suggest
      that the Cre/lox P system could tightly control expression of EGFP and HCV-C in
      vitro, which laid a solid foundation to conditionally activate expression of
      target gene(s) in transgenic mice by Cre-mediated site-specific recombination.

PMID- 15483750
TI  - Construction of the seed-coat cDNA microarray and screening of differentially
      expressed genes in barley.
AB  - Some barley mutants can synthesize neither anthocyanins nor proanthocyanidins in
      the seed coat, which is related to several genes in locus Ant13, but the exact
      model of action remains unknown. We used the cDNA microarray technology with
      barley transcription-deficient mutant (ant13-152) that does not synthesize
      proanthocyanidins as the tester, and its wild type genotype (Triumph) as the
      driver, to study this question. Six-thousand and forty-eight clones from the wild
      type Morex testa+pericarp cDNA library were amplified using PCR, and the DNA
      fragments were spotted on commercial amino-modified glass slide as microarray.
      The mRNAs from the developing seed coat (8-15 days) of both the mutant and the
      wild-type barley plants were isolated, and labeled respectively with Cy3-dUTP and
      Cy5-dUTP when reversely transcribed to cDNAs. The labeled cDNAs were used as
      probes, mixed at the same molar concentration, and hybridized with the DNA
      fragments on the slide. Seventy clones exhibiting marked differential expression
      (ratio>4) were identified from the microarray. All the 25 cDNA clones that showed
      an over-expression in wild type in comparison to the mutant ant13-152 were
      sequenced. It was found that most of these overexpressing clones were
      transcription/translation and hordein-associated genes. These results have laid a
      solid material basis for further elucidation of the metabolic pathway in
      proanthocyanidin synthesis in barley and likely other plants.

PMID- 15483751
TI  - The effect of bovine IFN-alpha on the immune response in guinea pigs vaccinated
      with DNA vaccine of foot-and-mouth disease virus.
AB  - In this study, we constructed recombinant plasmid pcDNA3.1/P12X3C3D including P1,
      2A, 3C, 3D and part of 2B gene of FMDV and pcDNA3.1/IFN containing the gene
      encoding bovine IFN-alpha. We inoculated the DNA vaccine pcDNA3.1/P12X3C3D with
      or without pcDNA3.1/IFN to evaluate the efficiency of this DNA vaccine and the
      immunogenicity of DNA vaccine enhanced by the co-delivery with pcDNA3.1/IFN.
      After two times of vaccination with DNA vaccine, all of guinea pigs were
      challenged with 103 ID50 FMDV type O. Anti-FMDV antibody levels were detected by
      ELISA and T lymphocyte proliferation response was tested by MTT assay. The result
      shows that guinea pigs inoculated by pcDNA3.1/P12X3C3D alone or with pcDNA3.1/IFN
      generated specific antibodies and induced an FMDV-specific T lymphocyte
      proliferation response. FMDV challenge tests showed that one in four guinea pigs
      immunized by pcDNA3.1/P12X3C3D with pcDNA3.1/IFN was protected from the FMDV
      serotype O infection. This result indicated that the efficiency of the DNA
      vaccine was enhanced by co-delivery with pcDNA3.1/IFN. However, the protection
      rate was considerably lower than that immunized with conventional FMD vaccine.

PMID- 15483752
TI  - Rapid purification of a new humanized single-chain Fv antibody/human interleukin
      2 fusion protein reactive against HER2 receptor.
AB  - Human embryonic kidney 293 cells were transfected with plasmid pcDNA-H520C9scFv
      rhIL-2 containing a chimeric cDNA encoding the humanized 520C9 scFv/recombinant
      human IL-2 fusion protein (H520C9scFv-rhIL-2). The transfected cells in plateau
      growing phase were cultured in serum-free medium for three days. The supernatant
      was collected, concentrated and purified using an affinity column packed with
      CNBr-activated Sepharose 4B coupled with anti-rhIL-2 mouse monoclonal antibody.
      The purified fusion protein was analyzed by ELISA, SDS-PAGE and Western blot. The
      fusion protein showed only one band in both silver stained electrophoresis gel
      and Western blot developed by ECL chemiluminescence system. Its molecular weight
      was confirmed to be about 45 kD. This fusion protein possessed binding
      specificity against p185 positive SKOV3 and B16/neu cells, and it might stimulate
      IL-2-dependent CTLL-2 cell proliferation as well.

PMID- 15483753
TI  - Comparative analysis of the hspA mutant and wild-type Synechocystis sp. strain
      PCC 6803 under salt stress: evaluation of the role of hspA in salt-stress
      management.
AB  - DNA microarray analysis has previously revealed that hspA, which encodes a small
      heat-shock protein, is the second most highly expressed gene under salt stress in
      Synechocystis sp. strain PCC 6803. Consequently, an hspA deletion mutant was
      studied under various salt stresses in order to identify a potential role of HspA
      in salt stress management. The mutant had a growth disadvantage under moderate
      salt stress. It lost the ability to develop tolerance to a lethal salt treatment
      by a moderate salt pre-treatment when the tolerance was evaluated by cell
      survival and the level of major soluble proteins, phycocyanins, while the wild
      type acquired tolerance. Under various salt stresses, the mutant failed to
      undergo the ultrastructural changes characteristic of wild-type cells. The
      mutant, which showed higher survival than the wild-type after a direct shift to
      lethal salt conditions, accumulated higher levels of groESL1 and groEL2
      transcripts and the corresponding proteins, GroES, GroEL1, and GroEL2, suggesting
      a role for these heat-shock proteins in conferring basal salt tolerance. Under
      salt stress, heat-shock genes, such as hspA, groEL2, and dnaK2, were
      transcriptionally induced and greatly stabilized, indicating a transcriptional
      and post-transcriptional mechanism of acclimation to salt stress involving these
      heat-shock genes.

PMID- 15483754
TI  - Carbon-11-methionine positron emission tomography imaging of chordoma.
AB  - OBJECTIVE: Chordoma is a rare malignant bone tumor that arises from notochord
      remnants. This is the first trial to investigate the utility of (11)C-methionine
      (MET) positron emission tomography (PET) in the imaging of chordoma before and
      after carbon-ion radiotherapy (CIRT). DESIGN AND PATIENTS: Fifteen patients with
      chordoma were investigated with MET-PET before and after CIRT and the findings
      analyzed visually and quantitatively. Tumor MET uptake was evaluated by tumor-to
      nontumor ratio (T/N ratio). RESULTS: In 12 (80%) patients chordoma was clearly
      visible in the baseline MET-PET study with a mean T/N ratio of 3.3+/-1.7. The MET
      uptake decreased significantly to 2.3+/-1.4 after CIRT ( P<0.05). A significant
      reduction in tumor MET uptake of 24% was observed after CIRT. Fourteen (93%)
      patients showed no local recurrence after CIRT with a median follow-up time of 20
      months. CONCLUSION: This study has demonstrated that MET-PET is feasible for
      imaging of chordoma. MET-PET could provide important tumor metabolic information
      for the therapeutic monitoring of chordoma after CIRT.

PMID- 15483755
TI  - Multiple rice body formation in the subacromial-subdeltoid bursa and knee joint.
AB  - Multiple rice body formation is an uncommon disorder which resembles synovial
      chondromatosis both radiologically and clinically. The clinical symptoms are
      usually non-specific. We report on a pathologically proven multiple rice body
      formation in both the left subacromial-subdeltoid bursa and knee joint in a 4
      year-old girl.

PMID- 15483756
TI  - [Clinical utility of EUS-FNA in upper gastrointestinal and mediastinal disease].
AB  - BACKGROUND: Endoscopic ultrasound (EUS)-guided fine-needle aspiration biopsy (EUS
      FNA) is increasingly used for the diagnosis of malignant and benign disease in
      the region of the upper GI tract. We prospectively investigated the clinical
      accuracy and safety of this method in unselected patients under routine
      conditions. PATIENTS AND METHODS: 101 consecutive patients (median 61.5 years; 56
      female) were enrolled in the study, in whom a total of 106 tissue biopsies were
      obtained by using EUS-FNA. Major indications for EUS-FNA were suspicious lesions
      located in the mediastinum, esophagus, stomach, pancreas, liver, biliary system,
      adrenals or retroperitoneum. A longitudinal echoendoscope (HITACHI FG-34UX)
      equipped with a standard 22G -aspiration needle was used. The aspirated specimens
      were analyzed further by using standard cytology and/or histology. Lymph-node
      biopsies were additionally subjected to flow-cytometry (FACS-light-chain
      restriction). Surgery was used for reference (where available). In the remaining
      cases the final diagnosis obtained by the clinical course and all available
      imaging and histologic informations (ultrasound, CT, MRT) was used for reference.
      RESULTS: EUS-FNA caused no serious complications. In 6/106 specimen (5.6 %) no
      sufficient cell material could be aspirated. In the remaining 100 specimens EUS
      FNA reached an overall sensitivity of 78 % and a specificity of 100 %, while the
      accuracy was 89 % and the positive and negative predictive values were 100 % and
      81 %, respectively. The greatest diagnostic accuracy was achieved in mediastinal
      and retroperitoneal lesions, while the accuracy of EUS-FNA in pancreatic lesions
      and perigastric lymph nodes was distinctly smaller (<80 %). Addition of FACS
      studies in patients with suspected malignant lymphoma increased the diagnostic
      accuracy in the small number of patients included in the study. CONCLUSION: EUS
      FNA improves the tissue-based diagnosis of suspicious lesions in locations that
      are difficult to access (e. g., posterior mediastinum). EUS-FNA is safe, while
      its diagnostic accuracy is relatively high. Our preliminary data suggest that
      flow-cytometry may improve the fine-needle based diagnosis of non-Hodgkin s
      lymphoma, which should be further investigated.

PMID- 15483757
TI  - [Tsutusgamushi fever after travel to Southeast Asia].
AB  - HISTORY AND CLINICAL FINDINGS: A 49-year-old travel guide fell ill during his
      return from a 6-week-stay in Vietnam, Myanmar and Thailand. He developed high
      fever and severe headache. On admission, the body temperature was at 39.5 degrees
      C with relative bradycardia. A black, crusted skin lesion of approximately 5 mm
      diameter was noted on the chest wall and was interpreted as an insect bite.
      INVESTIGATIONS: CRP and liver enzymes were elevated. Total leucocyte count was
      normal but the differential count showed a left shift and aneosinophilia. Imaging
      procedures revealed splenomegaly and small pleural effusions on both sides.
      TREATMENT AND COURSE: The patient was treated with a parenteral quinolone based
      on the initial suspicion of typhoid fever. Failure of this treatment and negative
      blood cultures raised concerns about the possibility of Tsutsugamushi fever,
      based on travel history and a re-evaluation of the skin lesion as an eschar.
      Tsutsugamushi fever was suspected on epidemiological and clinical grounds and was
      confirmed by the detection of specific IgM to Orienta tsutsugamushi and by
      seroconversion of IgG antibodies during follow-up. Even before immunodiagnostic
      confirmation was available, a course of doxycycline was started. This led to
      rapid improvement of the patient's condition. CONCLUSION: In febrile travellers
      returning from Southeast Asia, Tsutsugamushi fever has to be considered in the
      differential diagnosis. The causative agent, Orienta tsutsugamushi is transmitted
      by larvae of trombiculid mites (chiggers). Leading symptoms are fever continua,
      cephalgia, and a primary lesion (eschar) at the site of cutaneous inoculation.
      The Eschar is easily overlooked and has to be searched carefully. Diagnosis is
      confirmed by the detection of specific antibodies. However, serology may be
      negative in the beginning. Therefore, treatment with doxycycline should be
      initiated on clinical grounds.

PMID- 15483758
TI  - [Strychnine poisoning].
AB  - HISTORY AND ADMISSION FINDINGS: A 46-year-old man presented two hours after
      ingestion of about 250 mg strychnine with severe violent, generalized
      convulsions, triggered by external stimuli. During the convulsion-free periods
      there were no abnormal signs in the physical examination. INVESTIGATION: The
      presence of strychnine was confirmed by urine analysis with gas chromatography
      mass spectrometry. TREATMENT AND COURSE: Because diazepam as anticonvulsant of
      choice was not effective in abating the convulsions the patient was intubated. A
      combination with midazolam, fentanyl and pancuronium was effective in controlling
      the convulsions. The patient was discharged from ICU on day three. CONCLUSION:
      Fatal outcome of strychnine poisoning demands an aggressive management with early
      intubation, control of muscle tremors and prevention of rhabdomyolisis and renal
      failure.

PMID- 15483764
TI  - [Basal cell carcinoma -- An overview].

PMID- 15483765
TI  - [Change of burden of proof in severe treatment error--decision of the Federal
      Court on 4/27/2004].

PMID- 15483766
TI  - [Prevalence of functional pain of the back, the hip and the knee in adolescents.
      Results of a cross-sectional study].
AB  - OBJECTIVE: To determine the prevalence of functional back, hip and knee pain in
      adolescents. Risk factors which are associated with these complaints also should
      be detected. METHODS: A total of 2368 adolescents were included (1137 male, 1231
      female, age 14.5 +/- 0.7 years). The persons were interviewed in a self-reported
      questionnaire about episodes of back, hip and knee pain, furthermore
      sociodemographic information, activity in sports and consumption of legal drugs
      (tobacco and alcoholic beverages). All adolescents were examined by school
      doctors to determine back, hip and knee pathologies. RESULTS: A total of 62.4 %
      of the adolescents were suffering from musculo-skeletal pain (back 45.4 %, hip
      6.4 % and knee 33.6 %). The prevalence of pathological findings was: back 18.0 %,
      hip 2.7 % and knee 28.5 %. Summarized the prevalence of functional pain was 34.5
      % for back pain, 5.7 % for hip pain and 28.5 % for knee pain. There were
      significantly with functional pain associated factors. Male sex was significantly
      associated with functional back and hip pain. Knee pain was associated with
      sports activity. Adolescents who were visiting a high school and adolescents who
      were smoker had a significant higher prevalence of functional pain. CONCLUSION:
      The majority of functional back, hip and knee pain in adolescents must be
      classified as functional complaints. There is a significant association with
      female sex, visiting a high school and the consumption of legal drugs.

PMID- 15483767
TI  - [Clinical significance of stress reactivity for frequency of electric shock
      discharges in patients with implanted cardioverter-defibrillators].
AB  - BACKGROUND AND OBJECTIVE: Recent research indicates that discharges of implanted
      cardioverter-defibrillators (ICD) are triggered by psychosocial stress. This
      study examined the presence of patterns of psychophysiological stress reactivity
      in ICD-patients. Further more potential relationship between factors of stress
      reactivity and the frequency of implantable cardioverter-defibrillators
      discharges was investigated. PATIENTS AND METHODS: In 46 consecutive patients (38
      male, 8 female; age: 26-80 years) with implantable cardioverter-defibrillators
      the following parameters of physiological reactivity were measured in a
      standardised experimental stress test: Heart rate, skin conductance, muscle
      tension and respiratory activity. In a standardised interview anxiety
      sensitivity, depression, desire for control, stress load, and attitude towards
      the defibrillator were evaluated and quantified. The relationship between the
      mentioned parameters were examined with factor analysis to reveal patterns of
      psychophysiological reactivity. Potential relationship between
      psychophysiological factors and frequency of shock delivery was verified with
      linear regression analysis. RESULTS: Factor analysis revealed four independent
      psychophysiological traits. The factors were named "Play Dead Reflex", "Heart
      Phobia", "Negativism" and "Irritability". Linear regression model showed
      significant correlation between "Play Dead Reflex" and discharge frequency.
      CONCLUSIONS: Results confirm the presence of specific psychophysiological stress
      reaction patterns in ICD-patients. The stress reaction pattern "Play Dead Reflex"
      could be discussed as a potential risk factor in developing life-threatening
      tachyarrhythmias leading to an increase in defibrillator discharges in patients
      with ICD. This hypothesis should be considered in prospective studies and
      psychosomatic treatment of concerned patients.

PMID- 15483768
TI  - [Mucocele of the appendix. Incidental sonographic discovery and laparoscopic
      resection].
AB  - HISTORY AND ADMISSION FINDINGS: A 76-year-old currently asymptomatic man was
      admitted for routine sonography of the abdomen. 15 years he had had
      intermittently symptomatic cholecystolithiasis. 25 years before a colon contrast
      showed a normal coecum but no filling of the appendix. SUBSEQUENT INVESTIGATION:
      Sonographic examination showed the known cholecystolithisasis but additionally
      revealed as an incidental finding a tubular-cystic structure with a thin,
      echogenic wall and a hypoechogenic lumen. The lesion was located in the right
      upper quadrant, not compressible and arising from the coecum. Computed tomography
      confirmed a mucocele of the appendix without ascites and no inflammatory changes,
      peritoneal thickening or nodules. TREATMENT AND COURSE: Laparoscopic resection of
      the unruptured appendiceal mucocele together with cholestectomy was performed. On
      gross examination, the resected mucocele proved to be macroscopally an intact
      mass with a thin wall and full of white gelatinous material measuring 3 cm in
      diameter and 8 cm long. The histologic diagnosis was mucinous cystadenoma. The
      patient was discharged on the second postoperative day and recovered
      uneventfully. Because of the clear association of appendiceal cystadenoma with
      colorectal tumor a colonoscopy was performed which showed a normal colon.
      CONCLUSION: The differential diagnosis of a cystic mass in the right lower
      quadrant without previous appendectomy should include an appendiceal mucocele. If
      preoperatively there are no signs of malignancy, laparoscopic resection can be
      performed. In patients with histologic diagnosis of appendiceal cystadenoma: the
      colon should be examined to exclude synchronous colon tumors.

PMID- 15483770
TI  - [Disease modelling in diabetes mellitus].
AB  - Disease modelling increasingly plays an important role in planning and
      implementing medical decision making in diabetes care. For a general practitioner
      it is difficult to find access to application, benefit, arithmetic background and
      quality criteria of modelling. This review provides a comprehensive overview
      about the current methods in disease modelling in order to access quality
      criteria for disease modelling and modelling studies in diabetes care. The
      following criteria are essential for good quality in disease modelling: adequate
      choice of data sources, assessment of medical and economic data according to
      criteria of evidence-based medicine, reasonable time horizons, realistic use of
      discounting and inflation rates, representative target populations and a
      realistic perspective of the cost-benefit analysis. Furthermore, validation of
      disease models and the adequate use of those instruments are of importance.

PMID- 15483769
TI  - [Rational diagnosis of urolithiasis in daily practice].
AB  - Patients with renal colic are usually treated in emergency care units or by their
      family doctors and require immediate diagnosis and treatment. The life-time risk
      is up to 10 %. The prevalence amounts to 4.7 % in Germany. In addition to
      confirming the diagnosis and inducing an adequate pain therapy it is very
      important for patients to be directed correctly and, above all, prevention is
      important, too. Without treatment the recurrence rate ranges between 50 and 100
      %. Particularly, these principals should give useful advice, wherever patients
      are treated without urological department.

PMID- 15483771
TI  - [Anxiety and anxiety management in patients with implanted cardioverter
      defibrillators].

PMID- 15483772
TI  - [Cloning with therapeutic objectives].

PMID- 15483773
TI  - [Should a patient temporarily leave the hospital?].

PMID- 15483778
TI  - Subjective Global Assessment in chronic kidney disease: a review.
AB  - Nutritional assessment of patients with chronic kidney disease is a vital
      function of health care providers. Subjective Global Assessment (SGA) is a tool
      that uses 5 components of a medical history (weight change, dietary intake,
      gastrointestinal symptoms, functional capacity, disease and its relation to
      nutritional requirements) and 3 components of a brief physical examination (signs
      of fat and muscle wasting, nutrition-associated alternations in fluid balance) to
      assess nutritional status. SGA was originally used to predict outcomes in
      surgical patients; however, its use has gone beyond this function and population.
      In chronic kidney disease patients, SGA is incorporated into the complete
      nutritional assessment. Validation of SGA as a screening tool for surgical
      patients was done by Detsky et al in 1984. Since that time, SGA has been altered
      by different researchers and clinicians to better meet the needs of the patients
      they served. Validation of the altered SGA formats has not been thoroughly done.
      Further work in establishing validity and reliability of each version of SGA in
      different patient populations should be done to enable clinicians and researchers
      to properly use this nutritional assessment tool.

PMID- 15483779
TI  - Association of obesity with inflammation in chronic kidney disease: a cross
      sectional study.
AB  - OBJECTIVE: As adipose tissue releases inflammatory cytokines, obesity is
      associated with elevated C-reactive protein (CRP) levels in the general
      population. We examined the cross-sectional association of body mass index (BMI)
      with CRP in patients with chronic kidney disease (CKD). DESIGN: Cross-sectional
      study. SETTING AND PARTICIPANTS: Ninety-four CKD patients with varying levels of
      renal function seen at the University of Utah outpatient renal clinic were
      studied. METHODS: Data on demographics (age, gender, race), comorbidity (diabetes
      mellitus, hypertension, myocardial infarction/angina, cerebrovascular disease,
      peripheral vascular disease, and smoking) and anthropometry (height and weight)
      were obtained by patient interview and chart reviews. High-sensitivity CRP was
      measured by the N-latex assay on a BN II nephelometer. MAIN OUTCOME MEASURE: Risk
      factors of high CRP. RESULTS: In a multivariable logistic regression model, when
      compared with patients with a BMI < 25, the odds of CRP > 3.0 mg/L were 2.5-fold
      (95% CI, 1.02 to 5.99) higher in patients with BMI > or = 30. In a stepwise
      multiple linear regression model, BMI (regression coefficient [beta] = 0.06; 95%
      CI, 0.03 to 0.1; P < .01), serum creatinine (beta = 0.16; 95% CI, 0.04 to 0.3; P
      = .01) and age (beta = 0.01; 95% CI, -0.001 to 0.03; P = .05) were significantly
      associated with log transformed CRP. CONCLUSION: These data suggest that as in
      the general population, in CKD patients, obesity, a traditional risk factor for
      atherosclerosis, is associated with inflammation, a novel risk factor for
      atherosclerosis.

PMID- 15483781
TI  - In vitro clearance of trace elements via continuous renal replacement therapy.
AB  - OBJECTIVE: Trace element loss during continuous renal replacement therapy in
      patients with acute renal failure has not been quantified sufficiently. DESIGN:
      Trace element loss was quantified using an in vitro model of continuous
      venovenous hemofiltration. Bovine blood was used for the experiment, and the
      plasma was analyzed for its chromium, copper, selenium, manganese, and zinc
      content. Two different polysulfone hemodiafilters, a low-flux F8 and high-flux
      F70 were used, and tested at two different ultrafiltrate flow rates of 1 L/hr and
      2 L/hr, respectively. Trace element concentrations in the plasma and
      ultrafiltrate were analyzed using inductively coupled plasma mass spectrometry.
      The sieving coefficient and clearance of each trace element were calculated and
      compared between the two hemodiafilters. SETTING: In vitro bovine model of
      continuous venovenous hemofiltration. PATIENTS OR OTHER PARTICIPANTS: Not
      applicable. RESULTS: Mean sieving coefficients of both F8 and F70 hemodiafilters
      were similar for each trace element. Copper, chromium, manganese, selenium, and
      zinc all were detected in the ultrafiltrate. Estimated trace element loss using
      typical trace element blood concentrations and study-derived sieving coefficients
      suggest that daily losses of selenium are greater than what is replenished with a
      standard daily trace element supplement in total parenteral nutrition.
      CONCLUSION: These data suggest that the degree of continuous venovenous
      hemofiltration clearance chromium, copper, selenium, manganese, and zinc differ
      between elements and that selenium and copper might need to be replaced with
      doses that exceed typical supplementation guidelines.

PMID- 15483780
TI  - Adequate protein dietary restriction in diabetic and nondiabetic patients with
      chronic renal failure.
AB  - OBJECTIVE: To evaluate whether a dietary protein restriction is useful for
      slowing the progression of chronic renal failure (CRF) in diabetic and
      nondiabetic patients and to analyze the possible risk of malnutrition after such
      a dietary regimen. DESIGN: Prospective, randomized case-control clinical trial.
      SETTING: Nephrology outpatients. PATIENTS AND OTHER PARTICIPANTS: A total of 169
      patients, 89 affected with CRF and chronic hypertension and 80 affected with
      overt diabetic nephropathy (24 suffering from type 1 and 56 from type 2 diabetes)
      and chronic hypertension. INTERVENTION: Diabetic patients and nondiabetic
      patients were randomly divided into 2 groups: 40 diabetic patients received a low
      protein diet (0.8 g/kg/day) and 40 were maintained on a free protein diet;
      similarly, 44 nondiabetic patients received a low-protein diet (0.6 g/kg/day) and
      45 were maintained on a free protein diet. The investigation lasted 1 year. MAIN
      OUTCOME MEASURE: Renal function and nutritional status. RESULTS: At the end of
      the study, there were no statistically significant differences in renal function
      between treated and nontreated diabetic patients, whereas treated nondiabetic
      patients showed a lower decrease in renal function compared with the nontreated
      group. In both diabetic and nondiabetic patients, the mean body weight and
      obesity index decreased significantly in treated patients compared with
      nontreated ones. Serum albumin and prealbumin were stable in all patients during
      the whole study time, and there were no other signs of malnutrition. CONCLUSION:
      An adequate dietary protein restriction is accepted by patients, and it is well
      tolerated during a 12-month follow-up. Without any sign of malnutrition, it is
      possible to get near the ideal body weight and to reduce the obesity index and
      the body mass index, which are both well-established risk factors for developing
      cardiovascular pathology. In nondiabetic patients only, we observed a significant
      slowing of the progression of renal damage.

PMID- 15483782
TI  - Dietary habits and counseling focused on phosphate intake in hemodialysis
      patients with hyperphosphatemia.
AB  - OBJECTIVE: To evaluate the dietary habits of hemodialysis patients with
      hyperphosphatemia and the effects of a dietetic intervention focused on limiting
      dietary phosphate load. DESIGN: Cross-sectional dietary evaluation and
      prospective intervention study. SETTING: Hospital hemodialysis units of Pisa and
      Pistoia, Italy. Subjects Forty-three stable adult hemodialysis patients, 20 of
      whom had phosphorus serum levels >5.5 mg/dL. INTERVENTION: Analysis of dietary
      composition and of the effects of individual dietetic counseling in an attempt to
      reduce phosphorus intake while preserving the same protein intake. MAIN OUTCOME
      MEASURES: Differences in nutrient intake between normophosphatemic and
      hyperphosphatemic patients, and changes in dietary phosphorus and phosphorus
      protein ratio, serum phosphate, and calcium-phosphate product after dietetic
      intervention. RESULTS: No major differences in nutrient intake were detected
      between hyperphosphatemia and normophosphatemia patients, apart from a lower
      phosphorus-protein ratio (13.1 +/- 1.7 versus 14.1 +/- 2.1 mg/g, P < .05) in the
      former. After dietetic intervention in the hyperphosphatemia patients, phosphate
      and calcium intake decreased significantly (by 100 mg on average), whereas
      dietary protein did not change. A further decrease of the dietary phosphate
      protein ratio (12.5 +/- 1.8 mg/g, P < .05) also occurred. Serum phosphate showed
      a trend to decrease in the intervention group, whereas the serum calcium
      phosphate product decreased significantly (from 66.8 +/- 13.1 to 61.0 +/- 13.8
      mg2 /dL2 , P < .05). CONCLUSIONS: In compliant and motivated patients, individual
      dietetic counseling may be useful in reducing phosphate load and in limiting the
      phosphate burden related to an adequate protein intake, with a potentially
      favorable impact on calcium-phosphate retention. A phosphate-controlled diet has
      a role in an integrated therapeutic approach to hyperphosphatemia and positive
      calcium-phosphorus balance in hemodialysis patients.

PMID- 15483783
TI  - Cyclosporine enhances salt sensitivity of body water composition as assessed by
      impedance among psoriatic patients with normal renal function.
AB  - OBJECTIVE: Cyclosporine (CsA) therapy may be accompanied by a significant
      increase in blood pressure, either sodium (Na+) independent or Na+ dependent. The
      relationship between Na+ intake and body water distribution among patients
      treated with CsA has not been evaluated. We report the study, by bioelectrical
      impedance analysis (BIA), of water composition changes after dietary salt
      manipulations both before and during CsA treatment of psoriatic patients.
      METHODS: Ten normotensive psoriatic patients, ages 37 +/- 12 years (range, 19 to
      54), with normal renal function were included. Each patient was assessed by BIA
      in 2 phases, before (phase 1) and during (phase 2) CsA therapy (3 mg/kg/day). In
      both phases, each patient was assessed in basal conditions (basal1 and basal2),
      on day 7 of a low-sodium diet (LS1 and LS2; 20 mEq/day) and on day 7 of a high
      sodium diet (HS1 and HS2; 350 mEq/day). Plasma creatinine (Pcr), urinary volume
      excretion (Uv), urinary sodium (UNa+), urinary potassium (UK+), urinary
      osmolality (UOsmo), weight (Wt), resistance (R), reactance (Xc), total body water
      (TBW), extracellular water (ECW), intracellular water (ICW), Na:K exchangeable
      (Nae:Ke), phase angle (PA), and body cell mass (BCM) were evaluated. Blood
      pressure was monitored during 24 hours on the last day of each diet. Paired
      Student's t-test was used to analyze the different phases. RESULTS: Before CsA
      treatment, Wt, TBW and Nae:Ke were lower during LS1 than during basal1, whereas
      TBW was higher during HS1 than during LS1. During CsA, Wt, TBW, ECW, and Nae:Ke
      were lower during LS2 than during basal2, whereas ICW and PA were higher during
      LS2 than during basal2. HS2 showed higher TBW, ECW, and Nae:Ke and lower ICW, PA,
      and BCM than during LS2. Systolic blood pressure was higher during HS2 than
      during LS2 or HS1. In addition, diastolic blood pressure was higher during HS2
      than during HS1. CONCLUSION: Body hydration status was more sensitive to dietary
      salt fluctuations during CsA treatment than without CsA, and a high-sodium diet
      seemed to enhance the CsA-induced hypertension side effect. Moreover, patients on
      low sodium intake under CsA treatment displayed neither any disturbance of body
      water composition nor any blood pressure change. Our data suggest that a low
      sodium intake might be very useful in preventing undesirable pressure and volume
      changes brought about by CsA treatment.

PMID- 15483784
TI  - Supplementation with n-3 and n-6 polyunsaturated fatty acids: effects on
      lipoxygenase activity and clinical symptoms of pruritus in hemodialysis patients.
AB  - OBJECTIVE: To investigate the effect of supplementation with different sources of
      oils rich in long chain fatty acids, ie, fish oil (FO) and safflower oil (SO), on
      the production of leukotriene B4 (LTB4) by polymorphonuclear leukocytes (PMNLs)
      in hemodialysis patients and the consequent effects on the symptoms of pruritus.
      DESIGN: Randomized, prospective, double-blind study for 2 treatment groups.
      SETTING: Three Medical Center-affiliated units. PATIENTS: Twenty-two patients on
      maintenance hemodialysis, of both sexes, age > or = 20 years with complaint of
      dry and/or itchy skin. INTERVENTION: Two groups of patients receiving daily
      supplements of 6 g ethyl ester of FO or SO for 16 weeks. MAIN OUTCOME MEASURES:
      Red blood cell (RBC) fatty acid profile, LTB 4 production by PMNLs, and pruritus
      symptoms at baseline and after supplementation. RESULTS: After supplementation,
      the FO group had a higher RBC 22:6n3, total n-3 fatty acids, and ratio of total n
      3 to total n-6 fatty acids (P < .05) than the SO group. The change in LTB4
      production (pg/mL) from baseline to week 16 was 240.7 +/- 200.2 to 29.2 +/- 14.6
      in the FO group and from 171.1 +/- 121.7 to 31.9 +/- 14.7 in the SO group. The
      overall pruritus score change was 16.7 +/- 11.4 to 8.9 +/- 9.2 in the FO group
      and from 17.5 +/- 8.8 to 13.1 +/- 5.6 in the SO group. FO supplementation did not
      result in a significant specific effect on LTB4 production by the PMNLs. There
      was a nonsignificant decrease in the pruritus scores that could be clinically
      significant and important to patients suffering with this condition. CONCLUSION:
      Supplementation with FO results in significant incorporation of n-3 fatty acids
      in the RBCs. Intervention with both FO and SO resulted in a nonsignificant
      improvement of clinical symptoms of pruritus and a nonsignificant reduction in
      LTB 4 production by PMNLs in the hemodialysis patients. The percent decrease in
      total puritus score was greater for the FO group compared with the SO group.

PMID- 15483785
TI  - Nutritional status and oxidative processes in diabetic and nondiabetic peritoneal
      dialysis patients.
AB  - OBJECTIVE: The purpose of our study was to compare the level of malonyldialdehyde
      (MDA) and carbonyl groups (GC) in diabetic and nondiabetic peritoneal dialysis
      patients. DESIGN/SETTING: Prospective, observational study on peritoneal dialysis
      patients in a teaching hospital dialysis unit. PATIENTS: A total of 21 diabetic
      and 66 nondiabetic patients treated with peritoneal dialysis were examined in the
      study. Main outcome measures The assessment of nutritional status was determined
      by clinical, anthropometric, and biochemical methods. The GC content was
      determined by the 2,4-dinitrophenylohydrazine assay using the Garibaldi method.
      The MDA was measured using the colorimetric method (LPO-586). RESULTS: The plasma
      content of the GC and the MDA of peritoneal dialysis patients was significantly
      higher than in the healthy group (2.0 +/- 1.3 versus 1.3 +/- 0.4 nmol/mg protein
      and 3.8 +/- 1.4 versus 3.0 +/- 1.2 micromol/L). Moreover, the tendency toward
      increased levels of MDA and GC in the diabetic group in comparison with the
      nondiabetic group was noticed. Also, the highest values of GC and MDA were
      observed in severely malnourished patients. CONCLUSION: The increase in oxidative
      stress may be related to a degree of malnutrition.

PMID- 15483786
TI  - Muscle insulin-like growth factor status, body composition, and functional
      capacity in hemodialysis patients.
AB  - BACKGROUND: Hemodialysis (HD) patients typically have reduced muscle mass and
      diminished functional capacity. The role of the muscle insulin-like growth
      factors (IGFs), a principal anabolic system that is involved in protein synthesis
      and that has downregulation that is implicated in muscle loss in animal models of
      uremia, has previously not been assessed in vivo in HD patients. METHODS:
      Seventeen HD patients were compared cross-sectionally with 17 age-, sex-, and
      body mass index-matched healthy controls. Body composition was assessed by dual
      energy x-ray absorptiometry and bioelectrical impedance spectrometry; functional
      capacity by hand grip strength, quadriceps strength, and 30-second sit-to-stand
      test; systemic inflammation by tumor necrosis factor-alpha (TNF-alpha) and TNF
      receptor 1 (TNFR1); serum and muscle IGF-I and IGFBP-3 by radioimmunoassay; and
      fragmentation of serum IGFBP-3 by Western immunoblotting. RESULTS: Appendicular
      lean mass was significantly decreased in HD patients compared with controls (17.6
      +/- 0.9 versus 21.5 +/- 1.5 kg, P < .05), as were all measures of functional
      capacity (P < .01 to .001), and highly significant positive correlations between
      appendicular lean mass and functional capacity were evident (appendicular lean
      mass and hand-grip strength, quadriceps strength, 30-second sit-to-stand test,
      all P < .001). TNF-alpha and TNFR1 were elevated in patients (P < .001). Although
      serum IGF-I and IGFBP-3 levels did not differ between the groups (P = .295 and
      .379 respectively), fragmented IGFBP-3 levels were increased (53.1 +/- 16.0
      versus 29.81 +/- 15.3%, P < .005). In contrast, muscle IGF-I was substantially
      diminished in the patient group (n = 7) relative to control (n = 5) levels (0.84
      +/- 0.06 versus 2.78 +/- 1.80 pg/microg, P < .05). CONCLUSIONS: We provide
      evidence of reduced IGF-I in HD patients' skeletal muscle that may be a causal
      factor in the muscle wasting characteristic of this population. Future research
      should determine the exact consequences and causes of alterations to the muscle
      IGF system in HD patients.

PMID- 15483787
TI  - Patient education. Practical strategies for enhancing patient education in
      hemodialysis clinics.

PMID- 15483794
TI  - 2003 Hap Paul Award Paper of the International Society for Technology in
      Arthroplasty. Design and activity dependence of kinematics in fixed and mobile
      bearing knee arthroplasties.
AB  - Knee arthroplasty implants are designed with features that provide varying
      articular constraint over the range of flexion such that the pattern of knee
      motion may also vary. Because the motions of total knee implants have a direct
      influence on patient function and device longevity, it is important to understand
      how knee implants based on a variety of design philosophies perform in vivo.
      Fifty-nine knees in patients with 5 designs of implants were studied with
      fluoroscopic imaging during gait and stair-climbing activities. Many knees showed
      significantly different kinematics between the gait and stair activities, as well
      as differences from knees having other implant designs. The measured motions were
      consistent with the intrinsic constraint provided by the implant components and
      the variation in constraint over the flexion range.

PMID- 15483795
TI  - Total knee arthroplasty in obese patients: a comparison with a matched control
      group.
AB  - Thirty knees in 27 obese patients were matched to 30 knees in 27 nonobese
      patients, with both cohorts followed for a mean of approximately 15 years. Nine
      of 30 obese knees were revised, whereas 3 of 30 nonobese knees were revised, with
      Knee Society objective scores being higher in the nonobese group. There were more
      polyethylene insert revisions in the nonobese group, which may have been
      accounted for by a trend of higher activity levels in this group. The authors
      concluded that at long-term follow-up, although not statistically significant,
      there was a trend for obesity to influence the rate of aseptic loosening. This
      may occur because of increasing stress at the bone-prosthesis interface, whereas
      increased activity levels in the nonobese patients may adversely affect the
      longevity of the polyethylene insert.

PMID- 15483796
TI  - Preoperative demand matching is a valid indicator of patient activity after total
      hip arthroplasty.
AB  - The validity of preoperative demand matching as an indicator of patient activity
      following total hip arthroplasty (THA) was evaluated by studying 518 patients
      (mean age, 67 years; range, 26-92 years) who were assigned to 4 categories of
      decreasing demand: I (high demand), 68 patients (13%); II, 144 patients (28%);
      III, 281 patients (54%); and IV (low demand), 25 patients (5%). Preoperative
      Lahey Clinic Demand Category (as defined by age, weight, expected activity,
      health, and bone stock) was significantly correlated with self-reported,
      postoperative patient activity (P = .0038, R2 = .2024) and was much more
      predictive than any individual variable. Because patient activity is related to
      hip joint bearing surface wear, implant selection and resource allocation could
      be influenced by using demand matching to identify patients with high
      postoperative demand who may benefit from improvements in implant technology.
      Demand matching may also be used to stratify patient activity in long-term
      outcomes studies of THA.

PMID- 15483797
TI  - Early results with a total patellofemoral joint replacement arthroplasty
      prosthesis.
AB  - This report concerns a new prosthesis for total patellofemoral joint replacement.
      Patients severely disabled due to isolated patellofemoral arthritis in whom all
      other treatment options had been tried and failed, or were not indicated, became
      candidates for this surgery. Fifteen patients met these criteria and were
      followed an average of 3.75 years (range: 2.25-5.5 years). Using the Activities
      of Daily Living Scale, 14 of 15 patients (93%) had excellent (85%-100%) or good
      (75%-84%) results, and 1 was fair (65%-74%).

PMID- 15483798
TI  - The porous-coated anatomic total hip prosthesis: 11- to 13-year results.
AB  - Of 137 consecutive primary porous-coated anatomic (PCA) arthroplasties performed,
      complete data was available on 107 hips in 93 patients at an average of 12.4
      years (range, 11-13 years). The average Harris Hip Score improved from 44 to 85
      at final follow-up, with 78% good or excellent result. Thirteen percent (14 of
      107) of acetabular components and 4 porous ingrowth stems were deemed failures.
      Osteolytic lesions were seen in 7.5% (8 of 107) of acetabular components.
      Survivorship of the PCA prosthesis as a whole was 83% at 12.4 years. This first
      generation femoral stem performed well, with only 4 failures, all of which
      occurred in patients with avascular necrosis in which unrecognized pathologic
      changes in the proximal femur may have inhibited bone ingrowth. The majority of
      the failures can be attributed to aseptic loosening of the acetabular component.

PMID- 15483799
TI  - Proximal femoral allografts for bone deficiencies in revision hip arthroplasty: a
      medium-term follow-up study.
AB  - Fifteen patients who had undergone hip reconstruction using a proximal femoral
      allograft-prosthesis composite because of failed total hip arthroplasty were
      reviewed retrospectively. The average length of allograft was 11 cm. The average
      follow-up period was 7.6 years. Ten patients retained the allograft-prosthesis
      construct, yielding a success rate of 67% for the procedure. The average
      preoperative Harris Hip Score of all patients was 21.7 points. At the latest
      follow-up, the average hip score for 10 patients with retained allograft
      prosthesis composite was 81 points. Complications included junction nonunion
      (13%), allograft fracture (6.7%), loosening of acetabular component (6.7%),
      trochanteric escape (26.7%), allograft infection (20%), and allograft resorption
      (20%). Although proximal femoral allograft-prosthesis composite achieved good
      clinical results in most of the patients at medium-term follow-up, the late
      development of infection and resorption of the allograft warranted continued
      observation of patients who had undergone such procedures.

PMID- 15483800
TI  - Clinical and radiologic outcome of total hip arthroplasty performed by trainee
      compared with consultant orthopedic surgeons.
AB  - Data were prospectively collected on 139 total hip arthroplasties (THAs)
      performed by supervised specialist registrars (residents) and 397 THAs performed
      by consultants. The Harris Hip Score and data on comorbidity, blood loss,
      transfusion requirements, re-operation, dislocation, and death were recorded.
      Radiologic assessment of acetabular and femoral component alignment and
      cementation was made using 114 trainee radiographs that were available for review
      at 6 months. These were compared with 114 matched consultant radiographs. At 18
      months, there was no significant difference in clinical outcome. Acetabular
      anteversion was significantly less in trainee-performed THA. This article reveals
      no difference in the short-term clinical results of THA performed by consultants
      and supervised trainees. There is radiographic evidence of decreased anteversion
      of the acetabulum by trainees, although the dislocation rates are not different.
      Our results show that quality can be maintained while training juniors to perform
      surgery.

PMID- 15483801
TI  - Reliability of common knee injection sites with low-volume injections.
AB  - This study's purpose was to evaluate the reliability of knee injection sites with
      low-volume (2-3 cc) injection typical of viscosupplementation. This was a
      prospective study of 131 knees randomly assigned to 3 injection groups before to
      knee arthroscopy: SM-superomedial, superolateral, and lateral joint line (LJL).
      Needles were inserted to the hub, and aspiration was attempted before injection
      with 3 cc diluted methylene blue (MB). Injections then were graded at the time of
      arthroscopy as good, fair, or poor, depending on the intra-articular staining of
      MB. We conclude that a lateral joint line injection site may not be reliable for
      routine injections of low volumes into knees, because it results in good intra-
      articular delivery less than half of the time, with a high incidence of soft
      tissue infiltration.

PMID- 15483802
TI  - Total knee arthroplasty in patients with angular varus or valgus deformities of >
      or = 20 degrees.
AB  - Of 8,014 surgeries between January 1986 and August 2000, 82 primary total knee
      arthroplasties (TKAs) were performed on 75 patients with severe preoperative
      varus or valgus deformity of greater than or equal to 20 degrees with a minimum 2
      year follow-up time and a posterior cruciate retaining prosthesis. This study was
      designed to determine whether these patients (group A) could be as successful,
      using a Knee Society score (KSS) and alignment, as a matched control group (group
      B). There was no statistical difference in knee score, alignment, or revision.
      One revision was performed among the severely deformed. Knees that had severe
      angular deformities performed as well as deformity-free TKAs. Patients with
      excessive deformity should not be excluded from surgical correction solely based
      on this deformity.

PMID- 15483803
TI  - The use of bilobed porous-coated acetabular components without structural bone
      graft for type III acetabular defects in revision total hip arthroplasty: a
      prospective study with a minimum 2-year follow-up.
AB  - A prospective analysis was undertaken of 11 hips (in 11 patients) that underwent
      revision acetabuloplasties with bilobed, porous-coated, acetabular implants
      without the use of structural bone graft for type III acetabular defects. The
      average patient age was 66.3 years, with an average follow-up of 38 months
      (range, 24-49 months). No acetabular components required or are pending revision
      surgery. Average pain and hip scores improved from 8 and 36 preoperatively to 42
      and 89 postoperatively, respectively. Average leg-length differences decreased
      from 34 mm preoperatively to 7 mm postoperatively. The use of bilobed acetabular
      components without structural bone graft is a feasible alternative for
      reconstructing type III acetabular defects, and can provide good short-term
      clinical results, while reconstructing the hip center and maximizing host-implant
      contact.

PMID- 15483804
TI  - Patient satisfaction and functional status after aseptic versus septic revision
      total knee arthroplasty using the PROSTALAC articulating spacer.
AB  - This study compared the functional results of an articulating antibiotic spacer
      for 2-stage revision knee arthroplasty for infection, to the functional results
      of aseptic revision. One hundred twenty-five patients who underwent revision of
      total knee arthroplasty for infection and aseptic loosening were identified. All
      of the patients with infection were treated with the PROSTALAC system (DePuy). At
      a minimum 2-year follow-up, WOMAC, Oxford-12, SF-12, patient satisfaction data,
      Harris Hip Score knee scores, and range of motion were assessed. The 2 cohorts (4
      deaths in total, leaving 54 septic, 57 aseptic) were equivalent for age, gender,
      and comorbidity scores. At a mean of 41 months, none of the outcomes were
      significantly worse for the septic group, which had 2 recurrences of infection
      (4%). The satisfactory functional results of the PROSTALAC system may be related
      to the design features.

PMID- 15483805
TI  - Isolated patellar revisions for failed metal-backed components: 2- to 9-year
      follow-up.
AB  - Results of isolated patellar revisions for failed metal-backed patellae remain
      controversial. Isolated patellar revisions from April 1993 to April 2000 were
      assessed for complication rates, the Knee Society score (KSS), implant survival,
      and radiological loosening. Twenty-nine knees were revised in patients aged 71.0
      years (range, 61-87; SD, 6.2). At 67.0 months (range, 24-98 months; SD, 22.0), no
      patient underwent further revision. Knee scores improved by 26.5 (range, 9.0
      44.0; SD, 10.9) while function scores improved by 25.0 (range, 0-50.0; SD,14.5)
      over prerevision values. Early complications included 3 superficial wound
      infections, 1 hematoma, and a urinary tract infection in 1 patient. One patient
      had a subluxed patella. One patient had asymptomatic femoral osteolysis on
      radiological evaluation. Isolated patellar revisions can be performed in low
      demand, elderly patients with minimal patellar maltracking.

PMID- 15483806
TI  - Knee-simulator testing of conventional and cross-linked polyethylene tibial
      inserts.
AB  - We compared the resistance to delamination and to adhesive/abrasive wear of
      conventional and highly cross-linked polyethylene tibial inserts of a cruciate
      retaining total knee design using a knee simulator. Both groups were tested after
      aggressive, accelerated aging, and 1 set of conventional inserts was studied
      without aging. Aging oxidized the conventional, but not the highly cross-linked,
      inserts. The simulated normal gait testing lasted for 5 and 10 million cycles for
      the conventional and highly cross-linked inserts, respectively. Aged conventional
      inserts showed delaminations, whereas none were observed in the unaged
      conventional and aged cross-linked inserts. Wear rates measured by the
      gravimetric method were 9 +/- 2 mm3, 10 +/- 4 mm3, and 1 +/- 0 mm3 per million
      cycles; by the metrologic method, they were 8 +/- 1 mm3, 9 +/- 2 mm3, and 3 +/- 0
      mm3 for the unaged conventional, aged conventional, and aged highly crosslinked
      inserts, respectively. In the test model used, oxidation led to delamination,
      whereas increased cross-link density resulted in reduced adhesive/abrasive wear
      of tibial inserts.

PMID- 15483807
TI  - Zirconia femoral head fractures: a clinical and retrieval analysis.
AB  - Zirconia femoral heads provide increased fracture strength, but 343 zirconia head
      failures have been documented since 2000. Retrieval analysis of 6 fractured
      heads, 4 suspect heads, 4 control zirconia heads, and 2 failed alumina heads was
      performed. Zirconia failures have been isolated to heads sintered in a "tunnel"
      furnace introduced in 1998. The monoclinic composition at the taper surface of
      fractured and nonfractured heads was significantly elevated (21% to 68%) compared
      to that of control zirconia heads (less than 5%). Electron microscopy identified
      circular fracture footprints unique to the zirconia heads produced in the tunnel
      furnace. Cobalt chrome heads were used in the urgent revision setting due to
      Morse taper damage. Partial capsulectomy was performed in an effort to reduce
      future third body wear. Monoclinic phase transformation following implantation
      remains a potential mechanism of ceramic head failure. We recommend that patients
      with recalled zirconia heads be advised of a potential fracture risk.

PMID- 15483808
TI  - Tibiofemoral kinematic analysis of kneeling after total knee arthroplasty.
AB  - Some surgeons warn against kneeling after total knee arthroplasty (TKA), because
      limited clinical data exist. We describe the tibiofemoral contact position of TKA
      components during kneeling in vivo. Ten posterior-substituting (PS) and 10
      cruciate-retaining (CR) designs were examined using a radiographic image-matching
      technique. Movement from standing to kneeling at 90 degrees produced different
      responses. CR knees translated anteriorly (medial, 4 +/- 4 mm; lateral, 2 +/- 6
      mm). PS knees underwent little posterior translation (medial, 0.2 +/- 3 mm;
      lateral, 1 +/- 4 mm). Movement from 90 degrees to maximum flexion produced
      femoral posterior translation (CR medial, 5 +/- 4 mm; CR lateral, 5 +/- 4 mm; PS
      medial, 6 +/- 4 mm; PS lateral, 6 +/- 3 mm). The relationship between
      tibiofemoral contact position and flexion angle was more variable for CR (r2=.38)
      than for PS (r2=.64). Knee kinematics was similar to other deep-flexion weight
      bearing activities.

PMID- 15483809
TI  - Improved acetabular pressurization gives better cement penetration: in vivo
      measurements during total hip arthroplasty.
AB  - During total hip arthroplasty, the intraoperative cementation pressure was
      measured inside one of the acetabular anchorage holes. Patients were randomized
      to pressurization of cement with either a conventional pressurizer or a
      sequential method including individual pressurization of each anchorage hole. The
      pressure was correlated to the cement penetration measured on digital
      radiographs. The early peak pressures were higher for the sequential method,
      resulting in a significantly better penetration of 2.8 mm compared with 0.7 mm
      with the conventional pressurizer. We found a strong correlation between early
      peak cementation pressures and cement penetration into the cancellous bone of the
      anchoring holes, indicating a cause-effect relationship at this early stage. The
      highest peak pressures were achieved during the later cup insertion, but these
      pressures did not correlate with the cement penetration. We conclude that
      conventional methods for cement pressurization in the acetabulum may not be
      optimal.

PMID- 15483810
TI  - Applying the ASRA guidelines to the use of low-molecular-weight heparin
      thromboprophylaxis in major orthopedic surgery.
AB  - Although low-molecular-weight heparin (LMWH) is a widely used form of
      thromboprophylaxis in orthopedic surgery, concerns remain over the concomitant
      use of regional anesthesia (RA)/postoperative regional analgesia (PRA) stemming
      from reports in the 1990s of spinal hematoma associated with this combination.
      One of the objectives of the Second American Society of Regional Anesthesia
      (ASRA) Consensus Conference was to address the safety of LMWH in combination with
      neuraxial anesthesia. The guidelines are designed in part to help orthopedic
      surgeons already using or contemplating the use of LMWH prophylaxis to avoid or
      minimize potential complications arising from its use with RA/PRA. Clinicians
      should consult the ASRA guidelines for recommendations on total daily dose,
      timing of the first postoperative dose, and dose schedule for anticoagulants used
      in conjunction with RA/PRA.

PMID- 15483811
TI  - Stem fracture of conserve hemiarthroplasty.
AB  - Resurfacing hemiarthroplasty of the femoral head has been recommended as a bone
      preserving alternative to total hip arthroplasty for the management of
      osteonecrosis of the femoral head in the young patient. This case report
      describes failure of a cemented resurfacing hemiarthroplasty resulting from a
      fracture through the stem of the implant.

PMID- 15483812
TI  - Candida glabrata periprosthetic infection: a case report and literature review.
AB  - We present a case of an immunocompromised host who developed a Candida glabrata
      infection 20 years after her total knee arthroplasty. She was treated with
      extensive irrigation and debridement, followed by placement of an amphotericin B
      cement spacer supplemented with 2 months of oral variconazole. She ultimately
      underwent an above-knee amputation.

PMID- 15483813
TI  - Total knee arthroplasty in Meier-Gorlin syndrome.
AB  - This report documents the case of severe knee arthritis in a 33-year-old man with
      a rare genetic disorder, Meier-Gorlin syndrome. The purpose of this report is to
      present the first case of which we are aware consisting of a patient with this
      syndrome requiring total knee arthroplasty, illustrating the technical
      difficulties associated with knee arthroplasty in this syndrome, as well as to
      increase awareness of the orthopedic manifestations of this uncommon genetic
      syndrome.

PMID- 15483814
TI  - Reconstruction of the medial femoral condyle and medial collateral ligament in
      total knee arthroplasty using tendoachilles allograft with a calcaneal bone
      block.
AB  - Absence or compromise of the medial collateral ligament (MCL) in conjunction with
      osseous defects of the medial femoral condyle in total knee arthroplasty (TKA) is
      a challenging reconstructive problem. Treatment usually requires a highly
      constrained TKA with or without ligamentous reconstruction. To restore the medial
      femoral condylar bone and to provide ligamentous stability on the medial side of
      the knee, the authors present a technique for reconstruction of the medial
      femoral condyle and MCL using a tendoachilles allograft with a calcaneal bone
      block. The construct also can be augmented with a semitendinosus tendon
      autograft. Two illustrative cases and a review of the literature are presented.

PMID- 15483815
TI  - Secondary knee instability caused by fracture of the stabilizing insert in a dual
      articular total knee.
AB  - A case of a fractured polyethylene stabilizing insert causing secondary knee
      instability in a Dual-articular total knee arthroplasty (TKA) is presented. A 65
      year-old woman who underwent surgery with a Dual-articular TKA 4 years earlier
      had a well-functioning prosthesis until a fall, after which she began complaining
      of an intermittent, audible clicking; pain; and instability. At surgery, a
      fractured polyethylene peg was discovered, and the tibial insert was replaced. At
      follow-up, she remains asymptomatic. This is the first description of a fractured
      stabilizing insert in a Dual-articular knee.

PMID- 15484152
TI  - How to use ECG for decision support in the catheterization laboratory. Cases with
      ST-segment depression acute coronary syndrome.
AB  - Compared to ST-elevation myocardial infarction the ability of electrocardiography
      (ECG) to predict coronary anatomy in cases with acute coronary syndrome without
      ST-segment elevation is rather limited. However, certain sub-groups with distinct
      ECG patterns and varying risk profile can be defined. Differentiating ischaemic
      ECG patterns may help in clinical decision making for the individual patient.
      Modern technology makes it possible to get an interpretation of the ECG findings
      within minutes from an expert situated even in another country. Based on our
      experience an old method, 12-lead ECG, is still an important tool in clinical
      decision-making in patients with acute coronary syndrome in the catheterization
      laboratory.

PMID- 15484153
TI  - How to use ECG for decision support in the catheterization laboratory. Cases with
      inferior ST elevation myocardial infarction.
AB  - Treatment of acute myocardial infarction has changed considerably during the last
      few years with the introduction of primary coronary angioplasty. In the acute
      phase risk stratification is largely based on simple clinical parameters,
      laboratory markers of myocardial injury and 12-lead electrocardiography. The
      electrocardiogram is of crucial importance especially during the first few hours
      after initiation of chest pain when important therapeutic decisions are made.
      Biochemical markers of myocardial injury are usually not elevated at that time
      point. Cases with inferior ST-elevation myocardial infarction from our hospital
      are presented to show how anatomical interpretation of ECG recorded during chest
      pain helps to risk stratify patients.

PMID- 15484154
TI  - Abnormal QT prolongation and psychotropic drug therapy in psychiatric patients:
      significance of bradycardia-dependent QT prolongation.
AB  - Because many psychotropic drugs have electrophysiological properties similar to
      antiarrhythmic drugs, they might lengthen QT interval and cause torsades de
      pointes. Electrocardiograms were obtained in 688 psychiatric patients receiving
      psychotropic drugs. A QTc interval >460 ms was observed in 96 (14%) patients. To
      elucidate the heart rate dependence of QT prolongation, we measured QT intervals
      and the preceding R-R intervals at various heart rates by 24-hour Holter
      electrocardiogram in 97 patients. We estimated the QT intervals at the heart
      rates of 80 beats/min and 50 beats/min by the regression curve. A QT interval at
      the heart rate of 80 beats/min exceeded 400 ms in 14 (15%) patients and that at
      the heart rate of 50 beats/min exceeded 480 ms in additional 12 (12%) patients.
      Therefore, additional attention is needed for bradycardia-dependent QT
      prolongation even when the QT interval was not prolonged at usual heart rates.

PMID- 15484155
TI  - ST-recovery loop of exercise-induced ST deviation in the identification of
      coronary artery disease: which parameters should we measure?
AB  - This study aimed to characterize the ST-recovery loop and assess which range of
      heart rates (HRs) best discriminates between patients with and without
      significant coronary artery stenosis. Bicycle exercise tests were undertaken in
      44 men and 18 women with coronary artery disease (CAD) and in 59 controls (26
      men, 33 women) in the same age range with no signs of CAD. The ST level and the
      ST-segment slope were continuously monitored, and changes from rest to peak
      exercise and to 4 min after exercise, respectively, were calculated. Plotting the
      ST level against HR gives the STHR loop, characterized by the normalized area
      (NA(alpha)) circumscribed by the ST level during and after exercise from alpha%
      to 100% of the HR range. Eight values of alpha between 20% and 90% were
      investigated, and chest and extremity leads were investigated separately. Optimal
      alpha was found to be < or =70% in men and < or =30% in women. Change in ST
      segment slope was the only parameter that gave significant additional
      discriminating power in both men and women once the area had been taken into
      account. We conclude that NA(alpha) for extremity and chest leads have similar
      weights, and that a substantial part of the STHR loop should be taken into
      consideration, especially in women. NA(30) was superior to end-exercise ST
      depression and STHR loop orientation (as defined by the sign of NA(90)) in both
      men and women, and to ST/HR index in men, in identifying CAD.

PMID- 15484156
TI  - The 13th multiuse ECG lead: shouldn't we use it more often, and on the same hard
      copy or computer screen, as the other 12 leads?
AB  - Although the ECG diagnosis of cardiac pathology is well served by the employment
      of the standard 12 ECG leads, an occasional need arises that additional leads
      might provide a diagnostic advantage. To this effect it is proposed that a space
      is provided in the standard 12-lead ECG printed report for a "13th multiuse ECG
      lead"; such a lead, which will be referenced to the "central Wilson's terminal,"
      would provide additional information from various chest wall locations (V3R-V6R,
      posterior [left parascapular]) or other regions. Also such a lead could provide
      intracardiac electrograms via intracardiac recording wires or metallic or normal
      saline-filled catheters.

PMID- 15484157
TI  - Month-to-month and year-to-year reproducibility of high frequency QRS ECG
      signals.
AB  - High frequency electrocardiography analyzing the entire QRS complex in the
      frequency range of 150 to 250 Hz may prove useful in the detection of coronary
      artery disease, yet the long-term stability of these waveforms has not been fully
      characterized. Therefore, we prospectively investigated the reproducibility of
      the root mean squared voltage, kurtosis, and the presence versus absence of
      reduced amplitude zones in signal averaged 12-lead high frequency QRS recordings
      acquired in the supine position one month apart in 16 subjects and one year apart
      in 27 subjects. Reproducibility of root mean squared voltage and kurtosis was
      excellent over these time intervals in the limb leads, and acceptable in the
      precordial leads using both the V-lead and CR-lead derivations. The relative
      error of root mean squared voltage was 12% month-to-month and 16% year-to-year in
      the serial recordings when averaged over all 12 leads. Reduced amplitude zones
      were also reproducible up to a rate of 87% and 81%, respectively, for the month
      to-month and year-to-year recordings. We conclude that 12-lead high frequency QRS
      electrocardiograms are sufficiently reproducible for clinical use.

PMID- 15484158
TI  - Circadian changes in heart rate turbulence parameters.
AB  - Heart rate turbulence is a novel method to identify patients at risk of cardiac
      death, and to date, there are no data concerning its circadian changes. In 46
      coronary patients (mean age 63 +/- 8 years) with at least 100 ventricular
      premature beats in 24-hour Holter monitoring, turbulence onset, turbulence slope,
      and heart rate variability parameters were calculated in 3 equal 4-hour periods
      during morning, afternoon, and night. No circadian changes in turbulence onset
      values were found, while TS displayed significantly lower values during afternoon
      than during morning or night hours (5.08, vs. 7.08 and 7.99 ms/RR, respectively).
      Some heart rate variability parameters also showed lower values in the afternoon,
      not in the morning hours. In conclusion, in hospitalized patients with stable
      coronary artery disease, turbulence slope shows circadian pattern with lowest
      values observed in the afternoon when compared to morning and night hours.

PMID- 15484159
TI  - Sinus slowing caused by adenosine-5'-triphosphate in patients with and without
      sick sinus syndrome under various autonomic states.
AB  - Adenosine infusion can potentially be used as a diagnostic test for sick sinus
      syndrome (SSS) based on its negative chronotropic effects. Whether autonomic tone
      underlies adenosine's negative chronotropic effects remains unknown. This study
      was to investigate the bradycardiac response of sinus node to ATP in patients
      with and without clinical SSS by measuring atrial cycle length (ACL) before and
      after bolus of ATP in different states of autonomic tone. The negative
      chronotropic effect of ATP was assessed by comparing the mean ACL before ATP
      administration with the longest ACL after a bolus of ATP infusion (Delta ACL).
      Our results showed that Delta ACL in patients with SSS were significantly greater
      than that without SSS (P<.001) in all 4 states, and IHR in patients with SSS were
      significantly lower than calculated IHR (P<.0001). Moreover, there was no
      significant difference in Delta ACL between the 4 states in patients with SSS (P
      = .99). However, Delta ACL was significantly greater during isoproterenol
      infusion and after propranolol administration in patients without sinus node
      dysfunction, comparing with baseline state (P<.01), but not after combination of
      atropine (P = .33). Our results indicate that the negative chronotropic effect of
      ATP on sinus node is much more dramatic in patients with SSS, in which the
      intrinsic disease of sinus node is responsible for the abnormal adenosine
      mediated sinus arrest, and this effect is influenced by autonomic tone in
      patients without sinus node dysfunction but not in patients with SSS.

PMID- 15484160
TI  - Presence of intermittent J waves in multiple leads in relation to episode of
      atrial and ventricular fibrillation.
AB  - Brugada syndrome is characterized by J wave and ST-segment elevation of right
      precordial leads and causes idiopathic ventricular fibrillation. We experienced a
      patient of Brugada syndrome with prominent J wave and ST-segment elevation not
      only in V(1) to V(3) but also in many leads. He suffered spontaneous ventricular
      fibrillation and resuscitated by direct current. He has no structural heart
      disease.

PMID- 15484161
TI  - Radiofrequency catheter ablation for incessant atrioventricular nodal reentrant
      tachycardia normalized H-V block associated with tachycardia-induced
      cardiomyopathy.
AB  - A 30-year-old man was admitted for treatment of tachycardia-induced
      cardiomyopathy caused by incessant atrioventricular nodal reentrant tachycardia
      (AVNRT). An echocardiogram revealed dilatation of all cardiac chambers with
      severe globally depressed biventricular systolic function. During an
      electrophysiologic study, HV interval was prolonged to 118 ms by atrial
      extrastimulus and 2:1 HV block was documented during AVNRT. Four weeks after
      catheter ablation for AVNRT, an echocardiogram demonstrated regression of the
      wall motion abnormality of both ventricles and of their dimensions. In the
      electrophysiologic study, the HV conduction disturbance disappeared. So far, this
      is the first case in which tachycardia-induced cardiomyopathy was accompanied by
      transient His-Purkinje conduction abnormality.

PMID- 15484162
TI  - Right ventricle bipolar pacing may prevent appropriate biventricular pacing from
      two pacemakers. Case report.
AB  - This article reports on practical problems and possible solutions that may occur
      in case of upgrading a dual-chamber pacemaker by implanting a second left
      ventricular ventricular pacing, ventricular sensing, ventricular triggering (VVT)
      pacemaker. This therapeutic strategy was considered appropriate in the case of a
      73-year-old patient with severe heart failure, who was scheduled to undergo
      coronary artery bypass surgery. A right-sided, dual-chamber pacemaker had been
      already implanted to the patient. The duration of the paced QRS complex was 220
      ms and inter- and intraventricular dyssynchrony was documented in the
      echocardiographic study. We describe the methodological problems and possible
      solutions related to biventricular pacing following the abovementioned strategy.

PMID- 15484163
TI  - Exercise-induced left bundle branch block accompanied by chest pain. Correlation
      with coronary artery disease.
AB  - A case of a 25-year-old woman with familiar hypercholesterolemia, who was
      admitted complaining for chest pain on exertion, is presented. She underwent a
      treadmill stress test and during the exercise left bundle branch block with
      concomitant chest pain in low heart rate (105/min) was demonstrated. After these
      findings TL-201 scintigraphy with dipyridamole infusion was performed: Chest pain
      and left bundle branch block appeared again during the test, and the stress TL
      201 tomographic images showed reversible defect in the anterior wall. Finally,
      the young woman underwent coronary arteriography, which showed normal coronary
      vessels. The ergonovine test for coronary spasm was negative.

PMID- 15484171
TI  - Partnering for quality.
AB  - This article discusses efforts being made by multiple stakeholders to improve
      quality and safety in intensive care units (ICUs). The Leapfrog Group
      (Washington, DC), a consortium of purchasers, is reaching for quality by
      implementing safety standards. One standard, staffing ICUs with intensivists, is
      associated with a 30% reduction in hospital mortality and a 40% reduction in ICU
      mortality. While Leapfrog is addressing quality improvements on a structural
      level, JCAHO is developing empiric measures for ICU quality, which are being beta
      tested, to complement Leapfrogs' efforts. JCAHO used rigorously defined processes
      to develop and refine these measures. These measures include deep venous
      thrombosis prophylaxis, peptic ulcer disease prophylaxis, catheter-related blood
      stream infections, mortality and length of stay-APACHE III risk adjustment.
      Finally, ICU providers at Hopkins implemented an 8-step unit-based safety
      program. This comprehensive program is run at the unit level, works to improve
      safety culture, addresses staff safety concerns, partners hospital leaders with
      unit workers, helps staff implement improvement initiatives, uses rigorous data
      collection methods, and easily disseminated in other clinical areas. Providers
      can frame their efforts after 3 fundamental concepts from these initiatives:
      create a culture that supports quality and safety, standardize work processes by
      reducing complexity and using independent redundancy, and automate. The take home
      message is, when we come to work every day, we must be committed to quality and
      safety, and lead our teams to do the same.

PMID- 15484172
TI  - The effect of a managerial-based intervention on the occurrence of out-of-range
      measurements and mortality in intensive care units.
AB  - PURPOSE: To evaluate the effect of an organization-based managerial intervention
      on performance of intensive care units (ICUs). METHODS AND PARTICIPANTS:
      Prospective multicentre cluster-randomized study with an intervention at the
      level of ICU staff was carried out. The intervention comprised a set of
      managerial changes, concerning the nurses' level of skill discretion and
      participation in decision-making introduced during a period of six months. The
      ICU-performance was monitored before, during and after the intervention, in terms
      of mortality and occurrence of out-of-range-measurements (ORMs). The ORMs were
      defined as a derangement of systolic blood pressure (BP), heart rate (HR), oxygen
      saturation (SaO2) and urine output (Diur). Data were statistically analyzed by
      logistic regression with random effects due to ICUs. RESULTS: The overall ICU and
      hospital mortalities were 14% and 20%, the incidence of BP, HR, O2 and Diur ORM
      was respectively 46%, 38%, 28% and 48%. After adjusting for SAPSII, admission
      type and age the regression analyses revealed a positive effect of the
      intervention for all the six outcome variables. CONCLUSIONS: The intervention
      reduced both the ICU and hospital mortalities and the incidences of the out-of
      range measurements. Registering ORMs provides a feasible method for evaluating
      ICU performance and could help to optimize individual patient care.

PMID- 15484173
TI  - An empirical analysis of the decision-making of limiting life-sustaining
      treatment for patients with advanced chronic obstructive pulmonary disease in
      Hong Kong, China.
AB  - OBJECTIVES: To understand the prognostic and quality-of-life considerations
      surrounding life-sustaining treatment decisions for patients with advanced
      chronic obstructive pulmonary disease (COPD) in Hong Kong China. METHODS: A
      documentary review of 49 COPD patients and 19 patient case studies from the
      medical departments of 2 hospitals were undertaken to examine the practices of
      DNI decision-making (do not perform mechanical ventilation and cardiopulmonary
      resuscitation). Statistical, event, and thematic analyses were conducted to
      delineate the prognostic and quality-of-life factors that shaped the not for
      intubation and mechanical ventilation (DNI) decisions. RESULTS: Three major
      treatment-limiting decision-making patterns existed in practice: 1) Patient
      initiated and shared decision-making with physician (n = 14); 2) Physician
      initiated and shared decision-making with the patient/family members (n = 24);
      and 3) Physician-initiated DNI decision-making with patient family, but without
      patient participation due to mental incapacity (n = 11). Prognostic
      considerations include physiological parameters, performance status, concomitant
      diseases, therapeutic regimens, and the utilization of medical services. Three
      major themes were delineated regarding the way in which the patients evaluated
      their life quality in the context of DNI status. They are prognostic awareness,
      illness burdens, and existential concerns. DISCUSSION: A decision-making
      framework used by patients/families/physicians to limit life-sustaining
      treatments in patients with advanced COPD is delineated. Observations regarding
      how treatment limiting decision-making for patients with advanced chronic
      illnesses can be improved in Hong Kong are discussed.

PMID- 15484174
TI  - Patterns of chest physiotherapy in Australian Intensive Care Units.
AB  - PURPOSE: The aim of this study was to identify the availability of physiotherapy
      services in Australian Intensive Care Units (ICUs) and articulate the roles that
      physiotherapists and nursing staff play in the provision of chest physiotherapy.
      MATERIALS AND METHODS: Telephone interviews with 71 clinical nurse managers and 6
      physiotherapists of adult public Australian ICUs were undertaken. A structured
      interview schedule was developed from a review of the literature and a panel of
      experienced ICU clinicians and researchers to establish the frequency, components
      and personnel involved in the provision of chest physiotherapy. RESULTS: Almost
      90% (n = 67) of ICUs had physiotherapists available during the week but over 25%
      (n = 22) had "on-call" service only on weekends. Less than 10% had weekday (n =
      7) or weekend (n = 6) evening physiotherapy coverage. While nurses were involved
      in the provision of all aspects of chest physiotherapy, physiotherapists were
      primarily involved in airway suctioning, percussions, vibrations, positioning,
      and mobilization. CONCLUSIONS: The provision of chest physiotherapy services is
      often shared between physiotherapists and nurses, however, the actual therapies
      provided appears to vary depending on the provider. While strong evidence for
      chest physiotherapy procedures is lacking, the widespread use in the ICU suggests
      that it is an ideal setting for undertaking clinical research.

PMID- 15484175
TI  - Should procalcitonin be introduced in the diagnostic criteria for the systemic
      inflammatory response syndrome and sepsis?
AB  - PURPOSE: To define whether procalcitonin should be introduced in the diagnostic
      criteria of sepsis. METHODS: Procalcitonin was estimated in sera of 105
      critically ill patients by an immunochemiluminometric assay. Diagnosis was
      settled by 3 types of criteria: A, the American College of Chest
      Physicians/Society of Critical Care Medicine (ACCP/SCCM) 1992 criteria; B, the
      ACCP/SCCM criteria and concentrations of procalcitonin above 1.0 ng/mL as
      indicative of SIRS/sepsis; and C, the ACCP/SCCM criteria and concentrations of
      procalcitonin 0.5 to 1.1 ng/mL for SIRS and above 1.1 ng/mL for sepsis. RESULTS:
      Criteria A identified 50.5% of patients with SIRS, 18.1% with sepsis, 0.9% with
      severe sepsis and 22.9% with septic shock; respective diagnosis by criteria B
      were 26.7%, 9.5%, 10.5% and 25.7%; and respective diagnosis by criteria C were
      19.0%, 25.7%, 9.5%, and 25.7%. Sensitivity of concentrations between 0.5 ng/mL
      and 1.1 ng/mL was 25.6% for Systemic Inflammatory Response Syndrome (SIRS); and
      above 1.1 ng/mL 92.8% for sepsis. Sepsis-related death was associated with
      elevated procalcitonin upon presentation of a clinical syndrome. CONCLUSIONS:
      Despite the limited diagnostic value of procalcitonin for SIRS, concentrations of
      procalcitonin above 1.1 ng/mL are highly indicative for sepsis without, however,
      excluding the presence of SIRS.

PMID- 15484176
TI  - Interventions to reduce mortality among patients treated in intensive care units.
AB  - PURPOSE: Using sensitivity analysis to estimate the impact, in terms of patient
      lives, of the failure to use proven therapies known to reduce mortality in
      critically ill intensive care unit patients. MATERIALS AND METHODS: We identified
      high-impact interventions published in the last 5 years in the Journal of the
      American Medical Association or New England Journal of Medicine, extracted the
      absolute risk reduction associated with each intervention and gleaned the
      national incidence of each condition and the percent of the population not
      receiving the cited therapy from the literature. From this information, we
      calculated national estimates of the excess deaths from failure to use these
      therapies. RESULTS: With consistent and appropriate implementation of the 5 cited
      evidence-based interventions, we found a total of 167,819 lives could be saved
      per year, with a range of 137,670 to 197,965 lives saved per year. CONCLUSIONS:
      Mistakes of omission are common in the critical care setting and lead to
      significant preventable mortality. There is a significant gap between the
      discovery of effective interventions and their use in clinical practice. By
      viewing the delivery of healthcare as a science and increasing funding for health
      services research, we may be able to increase the use of effective therapies and,
      as a result, reduce patient mortality.

PMID- 15484177
TI  - Management of infections in critically ill neutropenic cancer patients.
AB  - Because of improving antineoplastic treatment options with increasing cure rates,
      prolonging survival, and improving quality of life, the reluctance to admit
      patients with malignant disease to an intensive care unit is not justified; thus,
      the number of patients with malignancies treated in intensive care units rises.
      The use of more aggressive anticancer regimens leads to an increase of attendant
      infections, which are the most frequent and often life-threatening complications
      in cancer patients. A multidisciplinary practical approach to evaluation and
      treatment is needed to optimize treatment results and to meet the various
      diagnostic and therapeutic challenges in this subset of patients on an intensive
      care unit.

PMID- 15484178
TI  - Continuous pentobarbital infusion in children is associated with high rates of
      complications.
AB  - PURPOSE: To evaluate the incidence and severity of complications related to
      continuous pentobarbital (PB) infusion for sedation in the Pediatric Intensive
      Care Unit (PICU). MATERIALS AND METHODS: We conducted a retrospective, chart
      review study. All patients admitted to the PICU from January 1997 through June
      1998 who received continuous IV PB infusion for sedation (n = 8) were included.
      RESULTS: All patients were intubated and mechanically ventilated prior to PB
      infusion. PB was used only as a second line sedative after a combination of an
      opioid and benzodiazepine failed to achieve adequate sedation. After initiation
      of PB, we were able to decrease or discontinue benzodiazepines and/or opioid
      doses and discontinue neuromuscular blocking drugs in all patients. We observed a
      high incidence of complications (62.5%) related to PB or the phenobarbital
      treatment used for barbiturate weaning, including blood pressure instability
      (25%), oversedation (12.5%), drug reaction (12.5%) and neurologic sequelae
      (12.5%). Discontinuation of the drug was required in 25% of the cases.
      CONCLUSIONS: We found continuous PB infusion to be an effective sedative for
      children when other drugs fail. However, we observed a high rate of clinically
      significant complications requiring discontinuation of the drug.

PMID- 15484179
TI  - Prestorage leukocyte reduction prevents the formation of microaggregates that
      occlude artificial capillary vessels.
AB  - PURPOSE: The passage behavior of stored blood through an artificial microchannel
      system, as a model of capillary vessels, was examined. MATERIALS AND METHODS:
      Using blood obtained from a total of 17 healthy volunteers, untreated and
      prestorage leukocyte reduced blood, or untreated and prestorage microfiltered (35
      microm-pore size) blood were stored, and then the passage behavior through the
      microchannels was evaluated. Also, using blood from 16 patients stored for about
      2 weeks, the effect of a leukocyte reduction filter, microfilter or mesh filter
      (175-210 microm-pore size) on the passage through the microchannels was examined.
      RESULTS: Untreated blood passed through the microchannels immediately after blood
      collection, but after 1 week occlusion of the microchannels occurred. Prestorage
      leukocyte reduced blood, however, passed through the microchannels for up to 6
      weeks. Occlusion of the microchannels occurred with both the untreated and
      prestorage microfiltered blood. Although filtration through a leukocyte reduction
      filter provided blood that can pass through the microchannels, occlusion occurred
      with blood filtered in other way. CONCLUSIONS: The present results show that
      stored blood produces abundant microaggregates, potentially occluding capillary
      vessels. These microaggregates are not formed after prestorage leukocyte
      reduction or can be removed by use of a leukocyte reduction filter.

PMID- 15484180
TI  - Transesophageal Pulsed Doppler echocardiography of pulmonary venous flow to
      assess left ventricular filling pressure in ventilated patients with acute
      respiratory distress syndrome.
AB  - OBJECTIVE: To determine whether the systolic fraction (SF) of the pulmonary
      venous flow (PVF), measured by transesophageal echocardiography (TEE) could be
      used to estimate the pulmonary artery occlusion pressure (PAOP). DESIGN:
      Prospective clinical investigation. PATIENTS: Nineteen intubated patients with
      ARDS. INTERVENTIONS: Doppler examinations with measurement of the SF of the PVF
      (ie, the systolic velocity-time integral expressed as a fraction of the sum of
      systolic and early diastolic velocity-time integrals) were performed
      simultaneously with measurements of PAOP via a right heart catheter at 0 cmH2O
      PEEP (ZEEP), at PEEP = 8 cmH20 and at PEEP = 16 cmH2O. MEASUREMENTS AND MAIN
      RESULTS: At ZEEP, PAOP was inversely correlated with the SF of the PVF (r = 
      .89). The difference of SF between the group with PAOP <18 mm Hg and the group
      with PAOP > or = 18 mm Hg was statistically significant (P < .05). A SF > or =
      55% predicted a PAOP < 15 mm Hg with a positive predictive value of 100% (95% CI
      = 63-100%). A SF < or = 40% predicted a PAOP > or =18 mm Hg with a positive
      predictive value of 100% (95% CI = 52-100%). At PEEP = 8 cm H20 (12 patients
      studied) and at PEEP = 16 cmH2O (10 patients studied), PAOP was inversely
      correlated with the SF of the PVF: r = -.84, and r = -.85, respectively.
      CONCLUSION: The SF of the PVF measured by Pulsed Doppler TEE seems to be a
      valuable index to estimate the left ventricular filling pressure in mechanically
      ventilated patients with ARDS.

PMID- 15484181
TI  - An unusual cause of renal failure in a liver transplant recipient.

PMID- 15484182
TI  - A new class of non-racemic chiral macrocycles: a conformational and synthetic
      study.
AB  - Amino alcohols have been used to introduce non-racemic chirality into macrocycles
      using a modular approach that relies on a Heck macrocyclisation reaction. A wide
      variety of macrocycles have been synthesised, and their structures studied using
      X-ray crystallography and molecular modelling. A fragmentation reaction
      encountered during the use of (S)-1,1-dimethylvalinol revealed that carboxylic
      acids generate acylals under reaction conditions often used for Heck reactions.

PMID- 15484183
TI  - Solids modeled by ab initio crystal field methods, part 22: the Fock matrix
      transformed supermolecule model and the structure determination of D-erythronic
      acid-3,4-carbonate.
AB  - To eliminate the cutoff effects in the supermolecule model (SM), the Fock matrix
      transformed supermolecule model (FTSM) is developed. In this model a cyclization
      of the cluster is performed by means of transformations of elements of the Fock
      matrix, thereby restoring the translational symmetry. Besides this fundamental
      enhancement, significant CPU time savings are realized because, in this new
      procedure, not all Fock matrix elements need to be calculated. The method is
      applied in a study of the structure of D-erythronic acid-3,4-carbonate in the
      crystal phase, where the new model is compared to the supermolecule model as well
      as the XRD experiment. The results are found to be in good agreement with
      experimental data.

PMID- 15484184
TI  - Prediction of physicochemical properties of organic molecules using van der Waals
      surface electrostatic potentials.
AB  - The generalized interaction properties function (GIPF) methodology developed by
      Politzer and coworkers, which calculated molecular surface electrostatic
      potential (MSESP) on a density envelope surface, was modified by calculating the
      MSESP on a much simpler van der Waals (vdW) surface of a molecule. In this work,
      vdW molecular surfaces were obtained from the fully optimized structures
      confirmed by frequency calculations at B3LYP/6-31G(d) level of theory. Multiple
      linear regressions for normal boiling point, heats of vaporization, heats of
      sublimation, heats of fusion, liquid density, and solid density were performed
      using GIPF variables from vdW model surface. Results from our model are compared
      with those from Politzer and coworkers. The surface-dependent beta (and gamma)
      values are dependent on the surface models but the surface-independent alpha and
      regression coefficients (r) are constant when vdW surface and density surface
      with 0.001 a.u. contour value are compared. This interesting phenomenon is
      explained by linear dependencies of GIPF variables.

PMID- 15484185
TI  - Characterization of isolated Ga2 molecules by resonance Raman spectroscopy and
      variations of Ga-Ga bonding.
AB  - Isolated Ga2 dimers were characterized in an argon matrix with the aid of
      resonance Raman and UV/Vis spectroscopy. The resonance Raman spectra gave
      evidence of not only the nu(Ga-Ga) fundamental, but also four overtones. Each of
      the signals exhibits 69Ga/71Ga isotopic splitting leading to the triplet pattern
      characteristic of two equivalent Ga atoms. On the basis of the experimental data,
      a harmonic frequency and anharmonicity constant have been determined for Ga2. An
      estimate of the dissociation energy on the assumption of a Morse-type potential
      energy curve results in a De value (upper limit) of about 145 kJ mol(-1). The
      force constant (64.8+/-0.3 N m(-1)) and dissociation energy of Ga2 are compared
      with those of other diatomics and those of molecules featuring Ga-Ga bonds.

PMID- 15484186
TI  - Global distribution of rotavirus serotypes/genotypes and its implication for the
      development and implementation of an effective rotavirus vaccine.
AB  - A safe and effective rotavirus vaccine is urgently needed, particularly in
      developing countries. Critical to vaccine development and implementation is a
      knowledge base concerning the epidemiology of rotavirus G and P
      serotypes/genotypes throughout the world. The temporal and geographical
      distribution of human rotavirus G and P types was reviewed by analysing a total
      of 45571 strains collected globally from 124 studies reported from 52 countries
      on five continents published between 1989 and 2004. Four common G types (G1, G2,
      G3 and G4) in conjunction with P[8] or P[4] represented over 88% of the strains
      analysed worldwide. In addition, serotype G9 viruses associated with P[8] or P[6]
      were shown to have emerged as the fourth globally important G type with the
      relative frequency of 4.1%. When the global G and/or P type distributions were
      divided into five continents/subcontinents, several characteristic features
      emerged. For example, the P[8]G1 represented over 70% of rotavirus infections in
      North America, Europe and Australia, but only about 30% of the infections in
      South America and Asia, and 23% in Africa. In addition, in Africa (i) the
      relative frequency of G8 was as high as that of the globally common G3 or G4,
      (ii) P[6] represented almost one-third of all P types identified and (iii) 27% of
      the infections were associated with rotavirus strains bearing unusual
      combinations such as P[6]G8 or P[4]G8. Furthermore, in South America, uncommon G5
      virus appeared to increase its epidemiological importance among children with
      diarrhea. Such findings have (i) confirmed the importance of continued active
      rotavirus strain surveillance in a variety of geographical settings and (ii)
      provided important considerations for the development and implementation of an
      effective rotavirus vaccine (e.g. a geographical P-G type adjustment in the
      formulation of next generation multivalent vaccines).

PMID- 15484187
TI  - Suppressive properties of human CD4+CD25+ regulatory T cells are dependent on
      CTLA-4 expression.
AB  - It has been demonstrated that T cells with regulatory properties are present
      within the peripheral blood CD4(+)CD25(+) T cell compartment. Here, we describe
      an original method to purify human CD4(+)CD25(+)CD152(+) T lymphocytes as living
      cells by forcing the exportation of CTLA-4 molecules stored in intracellular
      vesicules at the cell surface. By doing so, we demonstrate that CD4(+)CD25(+) T
      cells contain a smaller and more homogeneous population enriched in cells with in
      vitro regulatory activity. Moreover, we show that this enrichment in regulatory T
      cells is associated with an increased expression of Foxp3 and that
      CD4(+)CD25(+)CD152(+) T lymphocytes display a much stronger suppressive activity
      in controlling in vitro proliferation of alloantigen-specific T cells than
      CD4(+)CD25(+)CD152(-) T lymphocytes purified in parallel. Lastly, by purifying
      such cells expressing CTLA-4, we demonstrate that indeed CTLA-4 is involved in
      CD4(+)CD25(+)CD152(+) T cell regulatory activity, while suppressive cytokines are
      not.

PMID- 15484188
TI  - Paradoxical role of programmed death-1 ligand 2 in Th2 immune responses in vitro
      and in a mouse asthma model in vivo.
AB  - Programmed death-1 ligand 2 (PD-L2) is a ligand for programmed death-1 (PD-1), a
      receptor that plays an inhibitory role in T cell activation. Since previous
      studies have shown up-regulation of PD-L2 expression by Th2 cytokines, and asthma
      is driven by a Th2 response, we hypothesized that PD-L2 might be involved in
      regulation of the immune response in this disease. We have found that lungs from
      asthmatic mice had sustained up-regulation of PD-1 and PD-L2, with PD-L2
      primarily on dendritic cells. Although addition of PD-L2-Fc in vitro led to
      decreased T cell proliferation and cytokine production, administration of PD-L2
      Fc in vivo in a mouse asthma model resulted in elevated serum IgE levels,
      increased eosinophilic and lymphocytic infiltration into bronchoalveolar lavage
      fluid, higher number of cells in the draining lymph nodes, and production of IL-5
      and IL-13 from these cells. Although PD-1 was expressed on regulatory T cells, PD
      L2-Fc did not affect regulatory T cell activity in vitro. This study provides in
      vivo evidence of an exacerbated inflammatory response following PD-L2-Fc
      administration and indicates a potential role for this molecule in Th2-mediated
      diseases such as asthma.

PMID- 15484189
TI  - Functional involvement of P-selectin and MAdCAM-1 in the recruitment of
      alpha4beta7-integrin-expressing monocyte-like cells to the pregnant mouse uterus.
AB  - Leukocyte recruitment to the pregnant mouse uterus has been suggested to be
      associated with highly regulated expression of distinct patterns of vascular
      adhesion receptors. One of the most striking observations is the combined
      expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and P
      selectin by maternal vessels of the vascular zone during the critical period of
      initial placenta development. The predominant cell population within these
      vessels is of the monocyte/macrophage lineage and expresses the mucosal integrin
      alpha4beta7, which represents the ligand for MAdCAM-1; neutrophils and
      lymphocytes are rare. To directly assess the importance of identified adhesion
      receptors, we undertook long-term in vivo inhibition studies using monoclonal
      antibodies to inhibit the contribution of MAdCAM-1 in leukocyte trafficking to
      the decidua or to deplete alpha4beta7(+) leukocytes. In addition, implantation
      sites of mouse strains genetically deficient in specific adhesion receptors were
      investigated. Our results underline the importance of predicted adhesion pathways
      in the recruitment of monocyte-like cells, especially those expressing
      alpha4beta7. Interestingly, maternal/fetal units with inhibited recruitment of
      alpha4beta7(+) leukocytes or the absence of these cells are characterized by
      reduced size and frequency of uterine NK cells.

PMID- 15484190
TI  - Prostaglandin E2 modulates the functional responsiveness of human monocytes to
      chemokines.
AB  - Prostaglandin E(2) (PGE(2)) plays an important role in the immune response by
      modulating the complex interactions between leukocytes and tissue cells under
      inflammatory conditions. PGE(2) may possibly influence pro-inflammatory effects
      of chemokines and chemokine receptors that are among the main regulators of
      directional leukocyte migration. We analyzed whether PGE(2) affects chemokine
      receptor expression on human monocytes and their functional responsiveness to
      inflammatory chemokines. Expression of CCR5 on monocytes was significantly
      reduced, whereas CCR2 and CXCR4 expression were not affected by PGE(2). However,
      PGE(2 )treatment significantly increased the chemotactic response of monocytes to
      monocyte-chemoattractant protein-1 (MCP-1), RANTES and stromal cell-derived
      factor-1 (SDF-1). In addition, PGE(2) induced a higher calcium mobilization and
      actin polymerization upon chemokine stimulation. To better characterize PGE(2)
      effects, we used specific agonists for the PGE(2) receptors (EP(1) - EP(4))
      characterized so far. The 11-deoxy PGE(1), an EP(2) /EP(4 )ligand, could mimic
      the effects observed using PGE(2). In contrast, the EP(1 )agonist, sulprostone,
      had not effects on monocytes, indicating that the effects of PGE(2) are mediated
      by EP(2)/EP(4 )receptors. Monocytes acquire a higher functional responsiveness to
      MCP-1, RANTES and SDF-1 after exposure to PGE(2), independently of the level of
      chemokine receptor expression. This mechanism might enhance the local monocyte
      recruitment under inflammatory conditions, and suggests specific PGE(2) receptor
      EP(2)/EP(4) antagonists as novel agents for the treatment of inflammatory
      diseases.

PMID- 15484191
TI  - Homing of immature thymocytes to the subcapsular microenvironment within the
      thymus is not an absolute requirement for T cell development.
AB  - T cell development is thought to occur in distinct microenvironments within the
      thymus. Namely, the subcapsular zone, the cortex and the medulla have been
      described to support expansion of the immature thymocyte pool, positive selection
      of useful specificities and elimination of potentially self-reactive
      specificities, respectively. Consistent with this model, thymocytes show a highly
      ordered migration pattern and move into these niches in the expected sequence.
      Here we show that the chemokine receptor CCR9 plays a nonredundant role in the
      homing of immature thymocytes to the subcapsular zone. In CCR9-deficient mice, T
      cells in early stages of development do not accumulate in their physiological
      microenvironment underneath the thymic capsule and are instead homogeneously
      distributed across the thymic cortex. Remarkably, this abnormality does not
      result in a detectable defect in T cell development in CCR9-deficient mice,
      suggesting that the transit of immature thymocytes through the subcapsular
      microenvironment is not an absolute requirement for proper T cell development.

PMID- 15484192
TI  - Frontline: Peripheral priming of alloreactive T cells by the direct pathway of
      allorecognition.
AB  - Recent studies, though controversial, have suggested that secondary lymphoid
      organs may not constitute an essential site for the initiation of immune
      responses to transplant antigens. However, this issue has never been examined in
      the context of direct and indirect allorecognition. Here, we characterized immune
      responses arising in draining lymph nodes and skin allografts, in a murine model
      based on a single T cell clonotype where these two pathways can be independently
      studied. In this model, graft rejection by the direct or the indirect pathway
      occurred with similar kinetics, although initiation of the alloreactive responses
      was clearly different. During indirect responses, expansion and activation of
      alloreactive T cells were first observed in draining lymph nodes, at day 7 post
      transplant, and graft-infiltrating T cells were observed later, at day 11. In
      striking contrast, directly activated alloreactive T cells were detected at an
      early stage inside the graft, and only later in the draining lymph nodes, after
      skin allograft rejection was almost completed. These results suggest that
      sensitization of naive T cells through the direct pathway could take place
      outside secondary lymphoid organs.

PMID- 15484193
TI  - Phenotypic heterogeneity of antigen-specific CD4 T cells under different
      conditions of antigen persistence and antigen load.
AB  - The factors responsible for the phenotypic heterogeneity of memory CD4 T cells
      are unclear. In the present study, we have identified a third population of
      memory CD4 T cells characterized as CD45RA(+)CCR7(-) that, based on its
      replication history and the homeostatic proliferative capacity, was at an
      advanced stage of differentiation. Three different phenotypic patterns of memory
      CD4 T cell responses were delineated under different conditions of antigen (Ag)
      persistence and load using CD45RA and CCR7 as markers of memory T cells. Mono
      phenotypic CD45RA(-)CCR7(+) or CD45RA(-)CCR7(-) CD4 T cell responses were
      associated with conditions of Ag clearance (tetanus toxoid-specific CD4 T cell
      response) or Ag persistence and high load (chronic HIV-1 and primary CMV
      infections), respectively. Multi-phenotypic CD45RA(-)CCR7(+), CD45RA(-)CCR7(-)
      and CD45RA(+)CCR7(-) CD4 T cell responses were associated with protracted Ag
      exposure and low load (chronic CMV, EBV and HSV infections and HIV-1 infection in
      long-term nonprogressors). The mono-phenotypic CD45RA(-)CCR7(+) response was
      typical of central memory (T(CM)) IL-2-secreting CD4 T cells, the mono-phenotypic
      CD45RA(-)CCR7(-) response of effector memory (T(EM)) IFN-gamma-secreting CD4 T
      cells and the multi-phenotypic response of both IL-2- and IFN-gamma-secreting
      cells. The present results indicate that the heterogeneity of different Ag
      specific CD4 T cell responses is regulated by Ag exposure and Ag load.

PMID- 15484194
TI  - Nuclear repositioning marks the selective exclusion of lineage-inappropriate
      transcription factor loci during T helper cell differentiation.
AB  - To address how heritable patterns of gene expression are acquired during the
      differentiation of Th1 and Th2 cells, we analyzed the nuclear position of lineage
      restricted cytokine genes and their upstream regulators by 3-dimensional
      fluorescence in situ hybridization. During Th1 differentiation, GATA-3 and c-maf
      loci, which encode upstream regulators of Th2 cytokines, were progressively
      repositioned to centromeric heterochromatin as defined by a gamma-satellite
      repeat probe and/or the nuclear periphery, compartments that have been associated
      with transcriptional repression. A third transcription factor locus, T-bet, which
      controls Th1-specific programs, was subject to de novo CpG methylation in a Th2
      cell clone. In contrast, we did not find repositioning of the cytokine gene loci
      IL-2, IL-3, IL-4 or IFN-gamma during T helper cell differentiation. Instead, IFN
      gamma was constitutively associated with the nuclear periphery, even when primed
      for expression in Th1 cells. Our results suggest that Th1/Th2 lineage commitment
      and differentiation involve repositioning of the regulators of cytokine
      expression, rather than the cytokine genes themselves.

PMID- 15484195
TI  - Commentary: Priming of alloreactive T cells--where does it happen?
AB  - Host lymphocytes can recognize alloantigens directly on transplanted donor tissue
      or indirectly after these antigens are processed and presented on host APC. Here,
      we outline the features of alloresponses that distinguish them from responses to
      conventional antigens, then we discuss various study systems that have examined
      where the priming of alloreactive CD4(+) and CD8(+) T cells occurs. Finally, we
      discuss the implications of recent data which suggest that direct responses
      originate in the graft itself whereas indirect responses are initiated in the
      draining lymph nodes.

PMID- 15484196
TI  - Illuminating zinc in biological systems.
AB  - Zinc is the second most abundant transition metal in the human body, fulfilling a
      multitude of biological roles, but the mechanisms underlying its physiology are
      poorly understood. The lack of knowledge is, in part, due to the hitherto limited
      techniques available to track zinc in biological systems. The recent emergence of
      a number of zinc-specific molecular sensors has provided a new tool to image zinc
      in live cells and tissue samples. This contribution highlights the concepts
      behind using zinc-specific fluorescent molecular sensors to gain information
      about zinc action in biological samples, and provides representative examples of
      images recorded.

PMID- 15484197
TI  - Hydrogen-bonded polyrotaxane-like structure containing cyclic (H2O)4 in
      [Zn(OAc)2(mu-bpe)]2.H2O: X-ray and neutron diffraction studies.
AB  - The reaction of 4,4'-bipyridylethane (bpe) and 4,4'-dipyridyl disulfide (dpds)
      with Zn(OAc)2.2H2O has led to the formation of two coordination polymers,
      [Zn(OAc)2(mu-bpe)].2H2O (1) and [Zn(OAc)2(mu-dpds)] (2). Both the compounds have
      zigzag coordination polymeric structures as revealed by X-ray crystallography.
      However, the presence of two lattice water molecules in 1 results in an
      interesting difference between the crystal structures. In 1, the carboxylate
      carbonyl oxygen atoms of the Zn(OAc)2 groups from two different adjacent zigzag
      polymers and four lattice water molecules form 24-membered hydrogen-bonded rings
      (graph set notation, R6 (6)(24)). One of the two bpe ligands associated with each
      Zn(II) center passes through the center of this ring to form a two-dimensional
      hydrogen-bonded coordination polymeric structure. In the solid state, the
      adjacent 24-membered hydrogen-bonded rings further fuse together through O-H...O
      hydrogen bonds among four waters to form cyclic (H2O)4. This results in a one
      dimensional hydrogen-bonded ribbon-like polymer comprising fused alternating 24-
      and eight-membered O-H...O hydrogen-bonded rings. One of the bpe ligands passes
      through the center of the larger ring to produce an unexpected single self
      penetrating three-dimensional hydrogen-bonded network with polyrotaxane-like
      association. A neutron diffraction study provides a detailed description of the
      hydrogen bonds involved.

PMID- 15484198
TI  - By what mechanisms are metal cyclobutadiene complexes formed from alkynes?
AB  - The mechanism of formation of an eta4-cyclobutadiene complex from a metallacycle,
      generated by oxidative coupling of two acetylenes with the fragments CpRuCl,
      [CpRu(PH3)]+, CpCo, and CpRh, was investigated by means of DFT/B3LYP
      calculations. Two distinct pathways can be envisaged. 1) A multistep reaction,
      which can be denoted the Vollhardt mechanism, proceeding via a cyclopropenyl
      carbene and a tetrahedrane-type intermediate. 2) A one-step transformation
      involving the formation of a third M-C bond with rearrangement of the
      metallacyclic ring. Although path 2 is definitely favored over path 1, both
      pathways are energetically prohibitive unless substituents are present on the
      acetylene. For the CpRuCl system with HC triple bond CR the barrier varies with R
      in the series H approximately Ph>Me>>SiMe3. On going from H to SiMe3, the barrier
      for path 2 drops from 41.1 to 26.8 kcal mol(-1). This latter value is already
      reachable, in agreement with experiment. Whereas the reaction mechanisms
      involving the fragments CpCo, CpRh, and CpRuCl are very similar (but not
      identical owing to the additional ligand in CpRuCl), those of [CpRu(PH3)]+ reveal
      a modification with serious consequences. In both paths 1 and 2, the originally
      planar metallacycle experiences first a bending distortion induced by the sigma
      donor strength of P (in contrast to Cl), which compensates the loss of electrons
      from the ring brought about by bending. The bent metallacycle is already
      electronically asymmetric and thus the further course of the reaction is
      facilitated.

PMID- 15484199
TI  - Structure and dynamics of homoleptic beryllocenes: a solid-state 9Be and 13C NMR
      study.
AB  - The correlation between anisotropic 9Be NMR (quadrupolar and chemical shielding)
      interactions and the structure and dynamics in [Cp2Be], [Cp2*Be], and
      [(C5Me4H)2Be] is examined by solid-state 9Be NMR spectroscopy, as well as by ab
      initio and hybrid density functional theory calculations. The 9Be quadrupole
      coupling constants in the three compounds correspond well to the relative degrees
      of spherical ground-state electronic symmetry of the environment about beryllium.
      Theoretical computations of NMR interaction tensors are in excellent agreement
      with experimental values and aid in understanding the origins of NMR interaction
      tensors and their correlation to molecular symmetry. Variable-temperature (VT)
      9Be and 13C NMR experiments reveal a highly fluxional structure in the condensed
      phase of [Cp2Be]. In particular, the pathway by which the Cp rings of [Cp2Be]
      'invert' coordination modes is examined in detail using hybrid density functional
      theory in order to inspect variations of the 9Be NMR interaction tensors. The
      activation energy for the 'inversion' process is found to be 36.9 kJ mol(-1) from
      chemical exchange analysis of 13C VT CP/MAS NMR spectra. The low-temperature (ca.
      -100 degrees C) X-ray crystal structures of all three compounds have been
      collected and refined, and are in agreement with previously reported structures.
      In addition, the structure of the same Cp2Be crystal was determined at 20 degrees
      C and displays features consistent with increased intramolecular motion,
      supporting observations by 9Be VT NMR spectroscopy.

PMID- 15484200
TI  - In search of ultrastrong Bronsted neutral organic superacids: a DFT study on some
      cyclopentadiene derivatives.
AB  - An efficient but reasonably accurate B3LYP/6-311+G(d,p)//B3LYP/6-31G(d)
      computational procedure showed that pentasubstituted cyclopentadienes such as
      (CN)5C5H, (NO2)5C5H, and (NC)5C5H containing strongly electron-withdrawing groups
      are neutral organic superacids of unprecedented strength. The boldface denotes
      the atom attached to the cyclopentadiene framework. All of them exhibit
      prototropic tautomerism by forming somewhat more stable structures with C=NH,
      NO2H, and N=CH exocyclic fragments, respectively. The acidity (DeltaH(acid)) of
      these is lower, but only to a rather small extent. The DeltaH(acid) enthalpies of
      these last three tautomers are estimated to be 271, 276, and 282 kcal mol(-1),
      respectively. Hence, the most stable tautomers of (CN)5C5H and (NC)5C5H represent
      a legitimate target for synthetic chemists. On the other hand, (NO2)5C5H is less
      suitable for practical applications, because of its high energy density. The
      origin of the highly pronounced acidity of these compounds was analyzed by using
      the recently developed triadic formula. It is found that very high Koopmans'
      ionization energy (IE)n(Koop) of conjugate bases exerts a decisive influence on
      acidity. It follows as a corollary that the overwhelming effect leading to very
      high acidity is due to the properties of the final state. An alternative picture
      is offered by homodesmotic reactions, wherein the cyclic systems are compared
      with their linear counterparts. It is found that the acidity of cyclopentadiene
      (CP) is a consequence of aromatic stabilization in the CP- anion. The extreme
      acidity of pentacyanocyclopentadiene (CN)5C5H is due to aromatization of the five
      membered ring and a strong anionic resonance effect in the resultant conjugate
      base. The neutral organic superacids predicted by the present calculations may
      help to bridge the gap between existing very strong acids and bases.

PMID- 15484201
TI  - High-temperature synthesis of stable ordered mesoporous silica materials by using
      fluorocarbon-hydrocarbon surfactant mixtures.
AB  - Highly ordered hexagonal mesoporous silica materials (JLU-20) with uniform pore
      sizes have been successfully synthesized at high temperature (150-220 degrees C)
      by using fluorocarbon-hydrocarbon surfactant mixtures. The fluorocarbon
      hydrocarbon surfactant mixtures combine the advantages of both stable
      fluorocarbon surfactants and ordered hydrocarbon surfactants, giving ordered and
      stable mixed micelles at high temperature (150-220 degrees C). Mesoporous JLU-20
      shows extraordinary stability towards hydrothermal treatment (100 % steam at 800
      degrees C for 2 h or boiling water for 80 h), thermal treatment (calcination at
      1000 degrees C for 4 h), and toward mechanical treatment (compressed at 740 MPa).
      Transmission electron microscopy images of JLU-20 show well-ordered hexagonal
      arrays of mesopores with one-dimensional (1D) channels and further confirm that
      JLU-20 has a two-dimensional (2D) hexagonal (P6 mm) mesostructure. 29Si HR MAS
      NMR spectra of as-synthesized JLU-20 shows that JLU-20 is primarily made up of
      fully condensed Q4 silica units (delta=-112 ppm) with a small contribution from
      incompletely cross-linked Q3 (delta=-102 ppm) as deduced from the very high Q4/Q3
      ratio of 6.5, indicating that the mesoporous walls of JLU-20 are fully condensed.
      Such unique structural features should be directly attributed to the high
      temperature synthesis, which is responsible for the observed high thermal,
      hydrothermal, and mechanical stability of the mesoporous silica materials with
      well-ordered hexagonal symmetry. Furthermore, the concept of "high-temperature
      synthesis" is successfully extended to the preparation of three-dimensional (3D)
      cubic mesoporous silica materials by the assistance of a fluorocarbon surfactant
      as a co-template. The obtained material, designated JLU-21, has a well-ordered
      cubic Im3m mesostructure with fully condensed pore walls and shows unusually high
      hydrothermal stability, as compared with conventional cubic mesoporous silica
      materials such as SBA-16.

PMID- 15484202
TI  - Exercise manages fatigue during breast cancer treatment: a randomized controlled
      trial.
AB  - Fatigue is the most prevalent and debilitating symptom experienced by breast
      cancer patients receiving adjuvant chemotherapy or radiation therapy and few
      evidence-based treatments are available to manage this distressing side-effect.
      The purpose of this multi-institutional randomized controlled trial was to
      determine the effects of exercise on fatigue levels during treatment for breast
      cancer. Sedentary women (N=119) with Stage 0-III breast cancer receiving
      outpatient adjuvant chemotherapy or radiation therapy were randomized to a home
      based moderate-intensity walking exercise program or to usual care for the
      duration of their cancer treatment. Of participants randomized to exercise, 72%
      adhered to the exercise prescription; 61% of the usual care group adhered. The
      intention-to-treat analysis revealed no group differences in part because of a
      dilution of treatment effect as 39% of the usual care group exercised and 28% of
      the exercise group did not. When exercise participation was considered using the
      data analysis method of instrumental variables with principal stratification, a
      clinically important and statistically significant (p=0.03) effect of exercise on
      pretest-to-posttest change in fatigue levels was demonstrated. Adherence to a
      home-based moderate-intensity walking exercise program may effectively mitigate
      the high levels of fatigue prevalent during cancer treatment.

PMID- 15484203
TI  - Computational evidence for the enamine mechanism of intramolecular aldol
      reactions catalyzed by proline.

PMID- 15484204
TI  - Virus-like particles as HIV-1 vaccines.
AB  - Traditional successful antiviral vaccines have relied mostly on live-attenuated
      viruses. Live-attenuated HIV vaccine candidates are not ideal as they pose risks
      of reversion, recombination or mutations. Other current HIV vaccine candidates
      have difficulties generating broadly effective neutralising antibodies and
      cytotoxic T cell immune responses to primary HIV isolates. Virus-like-particles
      (VLPs) have been demonstrated to be safe to administer to animals and human
      patients as well as being potent and efficient stimulators of cellular and
      humoral immune responses. Therefore, VLPs are being considered as possible HIV
      vaccines. Chimeric HIV-1 VLPs constructed with either HIV or SIV capsid protein
      plus HIV immune epitopes and immuno-stimulatory molecules have further improved
      on early VLP designs, leading to enhanced immune stimulation. The administration
      of VLP vaccines via mucosal surfaces has also emerged as a promising strategy
      with which to elicit mucosal and systemic humoral and cellular immune responses.
      Additionally, new information on antigen processing and the presentation of
      particulate antigens by dendritic cells (DCs) has created new strategies for
      improved VLP vaccine candidates. This paper reviews the field of HIV-1 VLP
      vaccine development, focusing on recent studies that will likely uncover
      promising prospects for new HIV vaccines.

PMID- 15484205
TI  - Rate effects on the microindentation-based mechanical properties of oxidized,
      crosslinked, and highly crystalline ultrahigh-molecular-weight polyethylene.
AB  - The surface micromechanical properties of ultrahigh-molecular-weight polyethylene
      (UHMWPE) are critical in determining the wear, deformation, and fracture in the
      surface region. These properties have not been accessible to simple mechanical
      testing on a spatial scale relevant to these mechanical processes until recently.
      The structural factors associated with surface mechanical properties
      (crosslinking, oxidation state, local orientation of polymer, crystallinity,
      etc.) can be highly variable and localized and may vary on micron spatial scales
      or smaller. Furthermore, time/frequency-dependent behavior of the surface may
      have an important role in the overall surface mechanical behavior. Recent work
      has shown the utility of depth sensing microindentation/nanoindentation testing
      to interrogate local surface mechanical properties. The goal of the present study
      was to measure the effect of loading rate on the depth-sensing microindentation
      testing of UHMWPE. Three different UHMWPE materials (Hylamer, a large crystal
      material; GUR 1020, a standard medical-grade material; and Marathon, a
      crosslinked material) were tested using a microindentation method at loading
      rates ranging from 0.01 to 1 Hz. Similarly, a gamma-irradiated in air and 15-year
      shelf-aged tibial component was tested through its cross-section to assess the
      variations in mechanical properties with location and to compare the
      micromechanical profile with the oxidation profile. It was found that rate of
      testing affected the microhardness of each material, however, only GUR 1020 and
      Hylamer showed rate-dependent behavior for modulus and energy dissipation factor.
      Micromechanical profiles through oxidized regions of the tibial component showed
      a high correlation with the oxidation profile. Increases in modulus, hardness,
      and energy dissipation factor were seen with increasing oxidation and each
      property was loading-rate dependent. These results show that depth-sensing
      microindentation/nanoindentation testing on the micron scale provides highly
      consistent and reproducible measurements of surface mechanical properties. This
      scale of testing minimizes the potential variations caused by local heterogeneity
      in crystallinity, surface orientation, and other submicron structural features.

PMID- 15484207
TI  - Peroxynitrite decomposition catalyst, iron metalloporphyrin, reduces quinolinate
      induced neurotoxicity in rats.

PMID- 15484208
TI  - Metyrapone attenuates the sequential learning deficits but not monoamine
      depletions following d,l-fenfluramine administration to adult rats.
AB  - Fenfluramine (FEN) is a substituted amphetamine known for its anorectic effects,
      without the stimulatory or abuse potential associated with other amphetamine
      derivatives. FEN is a potent serotonin (5-HT) releaser and reuptake inhibitor and
      has been shown to cause depletions of 5-HT that can last days and even weeks
      after administration. Administration of FEN four times on a single day also
      causes a prolonged increase of corticosterone (CORT) that lasts approximately 72
      h following the first FEN dose. This dosing regimen also produces deficits in
      sequential learning as measured in the Cincinnati water maze (CWM). Adrenalectomy
      blocks this effect but removes more than CORT. Accordingly, the purpose of this
      study was to determine whether inhibiting glucocorticoid production, by
      administration of the 11 beta-hydroxylase inhibitor metyrapone (MET), will
      similarly attenuate or eliminate the sequential learning deficits seen with FEN
      exposure. MET (50 mg/kg) injections were administered 90 min prior to and for 3
      days after FEN (four doses given at 2-h intervals). Animals pretreated with MET
      and treated with FEN showed no sequential learning deficits when tested 1 week
      following FEN administration compared to FEN alone. The depletions of monoamines
      were similar following FEN administration, regardless of MET treatment. Taken
      together, this suggests that a potential mechanism for the sequential learning
      deficits in FEN-treated animals is a result of prolonged increases in CORT
      output.

PMID- 15484209
TI  - Fibroblast adhesion to micro- and nano-heterogeneous topography using diblock
      copolymers and homopolymers.
AB  - Polymeric substrates of different surface chemistry and length scales were found
      to have profound influence on cell adhesion. The adhesion of fibroblasts on
      surfaces of oxidized polystyrene (PS), on surfaces modified with random
      copolymers of PS and poly(methyl methacrylate) [P(S-r-MMA)] with topographic
      features, and chemically patterned surfaces that varied in lateral length scales
      from nanometers to microns were studied. Surfaces with heterogeneous topographies
      were generated from thin film mixtures of a block copolymer, PS-b-MMA, with
      homopolymers of PS and PMMA. The two homopolymers macroscopically phase separated
      and, with the addition of diblock copolymer, the size scales of the phases
      decreased to nanometer dimensions. Cell spreading area analysis showed that a
      thin film of oxidized PS surface promoted adhesion whereas a thin film of P(S-r
      MMA) surface did not. Fibroblast adhesion was examined on surfaces in which the
      lateral length scale varied from 60 nm to 6 microm. It was found that, as the
      lateral length scale between the oxidized PS surfaces decreased, cell spreading
      area and degree of actin stress fiber formation increased. In addition, scanning
      electron microscopy was used to evaluate the location of filopodia and
      lamellipodia. It was found that most of the filopodia and lamellipodia interacted
      with the oxidized PS surfaces. This can be attributed to both chemical and
      topographic surface interactions that prevent cells from interacting with the P(S
      r-MMA) at the base of the topographic features.

PMID- 15484210
TI  - Effect of neonatal isolation on the noradrenergic transduction system in the rat
      hippocampal slice.
AB  - Numerous studies suggest that early adverse experiences induce neurochemical,
      morphological, and functional changes in the hippocampus in adolescence and
      adulthood. The aim of this study was to identify the influence of neonatal
      isolation (NI) on noradrenaline (NA)-mediated intracellular calcium ([Ca(2+)](i))
      mobilization. To measure [Ca(2+)](i), we used the Ca(2+)-sensitive dye fura-2 and
      analysis by fluorescence microscopy. First, we examined the contributions of
      adrenergic receptor subtypes to the NA-stimulated increase in [Ca(2+)](i) in the
      granule cell layers of the dentate gyrus (DG) and in the pyramidal cell layers of
      the CA3 in the hippocampus. Second, we found that the NA-stimulated [Ca(2+)](i)
      increment was significantly decreased in response to NI in these hippocampal
      regions. In addition, we examined the influence of environmental enrichment (EE)
      after weaning on the decrease in the NA-stimulated [Ca(2+)](i) increment induced
      by NI. The administration of EE reversed the influence of NI on the NA-stimulated
      [Ca(2+)](i) increment in the CA3 pyramidal cell layer but not in the DG granular
      cell layer in the hippocampus. These findings suggest that NI and EE after
      weaning may modulate hippocampal function by altering adrenergic receptor
      mediated signal transduction during adolescence.

PMID- 15484211
TI  - Short-term morbidity of the upper limb after sentinel lymph node biopsy or
      axillary lymph node dissection for Stage I or II breast carcinoma.

PMID- 15484213
TI  - Measuring circulating neuroblastoma cells by quantitative reverse transcriptase
      polymerase chain reaction analysis.
AB  - BACKGROUND: Histologic examination of bone marrow (BM) is an accepted clinical
      standard for the detection of metastatic neuroblastoma (NB). Circulating tumor
      cells in peripheral blood (PB) derive from depots other than BM, and its
      measurement may provide additional information in the management of patients with
      NB. METHODS: One hundred twenty patients with Stage 4 NB were evaluated for tumor
      cell content in PB by quantitative reverse transcriptase-polymerase chain
      reaction (qRT-PCR) analysis of GD2 synthase mRNA with a sensitivity of 1 NB cell
      in 10(6) normal cells. These findings were correlated with qRT-PCR analysis of
      their simultaneously sampled BM aspirates and 5 standard modalities of disease
      detection (histology, computed tomography/magnetic resonance imaging, bone scan,
      metaiodobenzylguanidine scan, and urinary homovanillic acid/vanillylmandelic acid
      levels). RESULTS: Detection of GD2 synthase transcript was found in 62 patients:
      Eleven patients had positive (+) samples in their BM and PB (BM+PB+), 38 patients
      had BM+PB-negative (BM+PB-) specimens, and 13 patients had BM-PB+ samples. BM+PB+
      paired samples had the highest transcript levels. When the extent of disease was
      scored (from 0 to 5) according to the number of positive disease detection
      modalities, the magnitude of the transcript level correlated with disease score.
      Ninety-one percent of patients with BM+PB+ samples had evidence of disease in >/=
      3 modalities, whereas 97% of patients with BM-PB- samples and 100% of patients
      with BM-PB+ samples had low disease scores </= 2. Marker positivity in BM
      correlated with disease score. Patients who had positive marker in BM or PB had
      higher rates of relapse and death compared with patients who had negative marker.
      Kaplan-Meier analysis demonstrated a significantly greater risk of death for
      patients who had BM+PB+ specimens compared with patients who had BM-PB- samples
      (P = 0.03). CONCLUSIONS: BM monitoring should continue to be an integral part of
      disease follow-up for patients with Stage 4 NB. PB monitoring to complement tumor
      surveillance in the BM can be informative.

PMID- 15484214
TI  - Validation of the postoperative nomogram for 12-year sarcoma-specific mortality.
AB  - BACKGROUND: On the basis of a prospectively followed cohort of adult patients
      with primary soft tissue sarcoma (STS) who were treated at Memorial Sloan
      Kettering Cancer Center (MSKCC; New York, NY), a nomogram for predicting sarcoma
      specific mortality was developed. Although this nomogram was found to be accurate
      by internal validation tests, it had not been validated in an external patient
      cohort, and thus its universal applicability remained unproven. METHODS: Between
      1975 and 2002, 1167 adult patients (age > or = 16 years) underwent treatment for
      primary STS at the University of California-Los Angeles (UCLA; Los Angeles, CA).
      All patients treated with an ifosfamide-based chemotherapy protocol (n = 238)
      were excluded from the current analysis. The remaining 929 patients constituted
      the population on which the validation study was performed. The nomogram
      validation process comprised two activities. First, the extent of discrimination
      was quantified using the concordance index. Second, the level of calibration was
      assessed by grouping patients with respect to their nomogram-predicted mortality
      probabilities and then comparing group means with observed Kaplan-Meier estimates
      of disease-specific survival. RESULTS: With median follow-up intervals of 48
      months for all patients and 60 months for surviving patients, the 5-year and 10
      year disease-specific survival rates were 77% (95% confidence interval [CI], 74
      80%) and 71% (95% CI, 67-75%), respectively. Application of the nomogram to the
      UCLA data set yielded a concordance index of 0.76, and the observed
      correspondence between predicted and actual outcomes suggested a high level of
      calibration. CONCLUSIONS: In the current study, the MSKCC Sarcoma Nomogram was
      found to provide accurate survival predictions when it was applied to an external
      cohort of patients who were treated at UCLA.

PMID- 15484215
TI  - Neoadjuvant etoposide, ifosfamide, and cisplatin for the treatment of olfactory
      neuroblastoma.
AB  - BACKGROUND: The optimal chemotherapy regimen for the treatment of olfactory
      neuroblastoma has not been clearly defined. The purpose of the current study was
      to evaluate the efficacy of neoadjuvant chemotherapy with the combination of
      etoposide, ifosfamide, and cisplatin (VIP) for patients with olfactory
      neuroblastoma. METHODS: Eleven consecutive patients with newly diagnosed
      olfactory neuroblastoma were treated with etoposide (75 mg/m2), ifosfamide (1000
      mg/m2), and cisplatin (20 mg/m2) all administered intravenously on Days 1-5.
      Cycles were repeated every 21 days. Patients were excluded from analysis if they
      had previously received surgery or radiotherapy. RESULTS: Nine patients achieved
      objective responses (objective response rate, 82%; 95% confidence interval, 52
      95%), which included 2 complete responses and 7 partial responses. The major side
      effect was hematologic toxicity, with Grade 3/4 neutropenia observed after the
      receipt of 37% of all cycles and febrile neutropenia observed after the receipt
      of 2 cycles. All toxic events were reversible, and no chemotherapy-related deaths
      were documented. The median survival period was 18 months (range, 3-45 months).
      CONCLUSIONS: Neoadjuvant VIP chemotherapy was active in the treatment of
      olfactory neuroblastoma.

PMID- 15484216
TI  - Phase I clinical trial of fixed-dose rate infusional gemcitabine and dacarbazine
      in the treatment of advanced soft tissue sarcoma, with assessment of gemcitabine
      triphosphate accumulation.
AB  - BACKGROUND: In the current study, the authors set out to determine the dose
      limiting toxicity (DLT) and maximum tolerated dose (MTD) associated with a
      combination of gemcitabine and dacarbazine (DTIC) in patients with advanced soft
      tissue sarcoma (ASTS), to obtain preliminary information on the activity of this
      combination, and to explore possible pharmacodynamic interactions between
      gemcitabine and DTIC. METHODS: Every 2 weeks, 22 patients with refractory ASTS
      received fixed-dose rate gemcitabine (10 mg/m2/min) at escalating doses, which
      ranged from 800 mg/m2 to 2160 mg/m2, plus 500 mg/m2 DTIC. Plasma concentrations
      of gemcitabine and 2',2'-difluorodeoxyuridine, along with gemcitabine
      triphosphate (dFdCTP) levels in peripheral blood mononuclear cells (PBMCs), were
      evaluated during the course of treatment. RESULTS: Grade 3 elevation of
      transaminase and gamma-glutamyltransferase levels represented the DLT associated
      with the administration of 2160 mg/m2 gemcitabine plus 500 mg/m2 DTIC. This side
      effect was reversible, rather than cumulative, and did not exceed Grade 3 in its
      severity. The doses recommended for use in subsequent Phase II studies are 1800
      mg/m2 gemcitabine (administered over the course of 3 hours) and 500 mg/m2 DTIC.
      Hematologic toxicity was moderate, and nonhematologic side effects that did not
      exceed Grade 2 in severity included the following: asthenia (75% of patients),
      fever (59%), nausea (52%), stomatitis (48%), anorexia (44%), emesis (40%),
      flulike syndrome (37%), and erythematous rash (26%). Alopecia was common.
      Intracellular dFdCTP levels, which were evaluated in 6 patients, reached a mean
      maximum value of 209 pmol per 10(6) cells (standard deviation, 59 pmol per 10(6)
      cells) at the conclusion of gemcitabine administration. DTIC had a limited effect
      on the elimination of dFdCTP from PBMCs. Objective responses were observed in 5
      of the 19 patients who were evaluable for treatment efficacy. CONCLUSIONS: The
      combination of gemcitabine and DTIC possesses an acceptable toxicity profile and
      may warrant further investigation in patients with ASTS.

PMID- 15484218
TI  - Hematopoietic stem cell transplantation among patients with leukemia of all ages
      in Texas.
AB  - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an effective but
      expensive medical procedure to which some ethnic minorities, the elderly, and
      those without insurance have been shown to have limited access. The purpose of
      the current study was to determine whether socioeconomic factors were associated
      with HSCT usage rates in patients with leukemia. METHODS: The authors identified
      6574 patients with acute lymphocytic leukemia, chronic lymphocytic leukemia,
      acute myelogenous leukemia, chronic myelogenous leukemia, or other leukemias from
      the 1999 Texas Hospital Inpatient Discharge Public Use Data File. Of these
      patients, 1604 received an autologous or allogeneic HSCT. The authors assessed
      patients' ethnicity, payer status, age, gender, and comorbid medical conditions.
      Logistic regression was used to control for patient characteristics and to
      evaluate associations among payer status, ethnicity, and HSCT use. P < or = 0.05
      indicated statistical significance. RESULTS: Patients who self-paid had the
      highest rate of HSCT use in all age groups (32%; P < or = 0.01) and in the adult
      group (36%; P = 0.11). Elderly patients with Medicare had a low rate of HSCT use
      (17%; P = 0.13). Logistic regression showed no statistically significant
      associations between payer status or ethnicity and HSCT use. However, elderly
      women were significantly less likely to undergo HSCT than elderly men (odds
      ratio, 0.34; P < or = 0.01). CONCLUSIONS: The lack of statistically significant
      differences in HSCT use among adult patients with leukemia was surprising because
      previous studies had shown differences in HSCT by ethnicity and insurance.

PMID- 15484217
TI  - Quality of life impact of three different doses of suramin in patients with
      metastatic hormone-refractory prostate carcinoma: results of Intergroup
      O159/Cancer and Leukemia Group B 9480.
AB  - BACKGROUND: Research has suggested that men with hormone-refractory prostate
      carcinoma have a lower quality of life (QOL) compared with men who have hormone
      sensitive prostate carcinoma and that quality of life (QOL) steadily declines
      over the last year of life for men with prostate carcinoma. The primary purpose
      of the current study was to evaluate whether there was evidence of palliative
      effects associated with suramin at any of the three doses administered in the
      original clinical trial. METHODS: Patients with histologically confirmed advanced
      hormone-refractory adenocarcinoma of the prostate were randomized to receive
      suramin at a low dose (n = 129; median age, 69 years), an intermediate dose (n =
      129; median age, 71 years), or a high dose (n = 127; median age, 70 years) as
      part of the Intergroup 0159/Cancer and Leukemia Group B 9480 trial. Patients
      completed a battery of assessment tools, including the Functional Assessment of
      Cancer Therapy (FACT)-Prostate, the Center for Epidemiological Studies-Depression
      Scale (CES-D), the Brief Pain Inventory, and an opioid medication log, at
      baseline, on Day 1 of the sixth week of active therapy, during the second week
      after treatment termination, and 3 months after administration of the final
      suramin dose. RESULTS: Patients who received low-dose suramin reported
      improvement in QOL (FACT-General: P < 0.01; FACT-Treatment Outcome Index: P <
      0.01) and decreased levels of depression (CES-D: P < 0.0006) during treatment
      compared with patients in the intermediate- and high-dose arms. After treatment,
      all groups experienced equal decreases in FACT and CES-D scores. CONCLUSIONS: The
      pattern of results suggests that the lowest dose of suramin administered had a
      palliative effect in terms of improvement in QOL and decreased levels of
      depression and that this effect was lost once suramin was discontinued.

PMID- 15484219
TI  - Identification and phenotypic characterization of a subpopulation of T84 human
      colon cancer cells, after selection on activated endothelial cells.
AB  - The extravasation of metastatic cells is regulated by molecular events involving
      the initial adhesion of tumor cells to the endothelium and subsequently the
      migration of the cells in the host connective tissue. The differences in
      metastatic ability could be attributed to properties intrinsic of the various
      primary tumor types. Thus, the clonal selection of neoplastic cells during cancer
      progression results in cells better equipped for survival and formation of
      colonies in secondary sites. A cell line (T84SF) exhibiting an altered phenotypic
      appearance was selected from a colon cancer cell line (T84) by repetitive plating
      on TNFalpha-activated human endothelial cells and subsequent selection for
      adherent cells. Cell growth, motility, chemoinvasive abilities, tyrosine
      phosphorylation signaling, and the metastasis formation in nude mice of the two
      cell lines was compared. T84SF cells displayed in vitro an higher proliferation
      rate and a more invasive behavior compared to the parental cells while formed in
      vivo a greater number of metastatic colonies in nude mice. As concerns the
      signaling underlying the phenotypes of the selected cells, we examined the
      general tyrosine phosphorylation levels in both cell lines. Our results indicate
      that T84SF have an increased basal tyrosine phosphorylation of several proteins
      among which src kinase was identified. Treatment of cells with a specific
      inhibitor of src activity caused a greater in vitro inhibition of proliferation
      and invasive properties of T84 parental cells with respect to T84SF cells and
      diminished metastasis formation in vivo. Altogether, these data provide evidences
      that this new cell line may be valuable for identifying molecular mechanisms
      involved in the metastatic progression of colon cancer.

PMID- 15484220
TI  - Intraductal biopsy for diagnosis and treatment of intraductal lesions of the
      breast.
AB  - BACKGROUND: Bloody nipple discharge is a significant clue in the detection of
      ductal carcinoma of the breast. In the past, pathologic diagnoses were obtained
      exclusively via excision, but recently developed mammoscopic techniques have been
      found to yield valuable information relating to the diagnosis of intraductal
      lesions. METHODS: Mammary duct endoscopy (i.e., mammoscopy) was performed a
      combined total of 407 times for 295 patients who experienced nipple discharge.
      Intraductal breast biopsy (IDBB) under mammoscopic observation was performed in
      193 intraductal papillomas (from a total of 107 patients) and 30 ductal
      carcinomas (from a total of 27 patients); IDBB was performed a combined total of
      36 times in the 27 patients who had breast carcinoma and yielded 21 diagnostic
      specimens (58.3%). In addition, the therapeutic value of IDBB was assessed in 70
      patients with intraductal papilloma who had undergone more than 3 years of follow
      up; these 70 patients harbored a combined total of 75 intraductal papillomas.
      RESULTS: IDBB correctly identified the presence of carcinoma in 9 of 27 patients
      (33.3%); 7 other lesions (25.9%) were placed in the suspected carcinoma (i.e.,
      atypical papillary lesion) category, and 5 (18.5%) were identified as intraductal
      papillomas. Using IDBB, it was difficult to collect diagnostic specimens from
      patients with breast carcinoma, because of the location and weak tissue
      cohesiveness of these lesions compared with intraductal papillomas. The 193
      intraductal biopsies performed on intraductal papillomas yielded only 20
      specimens that were insufficient for diagnosis. IDBB exhibited therapeutic
      efficacy in 54 of 70 patients with intraductal papilloma (77.6%) who had more
      than 3 years of clinical follow-up. Therapeutic results tended to be less
      favorable for patients who had intraductal lesions in multiple duct lobular
      units. CONCLUSIONS: Mammoscopy can contribute not only to the diagnosis of cases
      of nipple discharge but also to the treatment of intraductal papilloma.

PMID- 15484221
TI  - HPLC quantification of metoprolol with solid-phase extraction for the drug
      monitoring of pediatric patients.
AB  - Although the analytical literature seems abundant for the determination of
      metoprolol in human plasma, a method using standard equipment providing a
      sensitive and simple high-performance liquid chromatographic (HPLC) method for
      limited blood volume, e.g. where 1 mL of blood in a 1 kg infant equals 70 mL of
      adult blood volume, has rarely been addressed. Therefore, in 500 microL of
      plasma, metoprolol was extracted using an internal standard and solid-phase
      extraction columns. Chromatographic analysis was performed on a Spherisorb C(6)
      column (5 microm particle size) at ambient temperature and fluorimetric detection
      with an excitation wavelength of 225 nm, and emission wavelength of 310 nm. The
      mobile phase [30% acetonitrile and 70% 0.25 m potassium acetate buffer (pH 4)]
      was pumped with 1 mL/min. Metoprolol recovery was determined at 73.0 +/- 20.5%,
      and the limit of quantitation was 2.4 ng/mL. Precision values of intra- and inter
      assay were below 15.5% and those for accuracy were between 90 and 110%. This
      method was developed for monitoring and determination of pharmacokinetic
      parameters of metoprolol in pediatric patients and therefore metoprolol plasma
      concentrations in a 2-year-old child with ventricular tachycardia are reported. .

PMID- 15484222
TI  - Social anxiety disorder in callers to the Anxiety Disorders Association of
      America.
AB  - Social anxiety disorder (SAD) is among the most common anxiety disorders with a
      lifetime prevalence of up to 16%. Among callers to the Anxiety Disorders
      Association of America (ADAA), we surveyed 1,000 participants using a 97-item
      questionnaire to understand the characteristics of participants with SAD and
      subthreshold SAD (SSAD). Current prevalence rates of SAD (n=295) and SSAD (n=41)
      were 29.5% and 4.1%, respectively. SAD and SSAD participants were more likely to
      be younger, single, with less education and lower income than their no axis-I
      psychiatric-disorder controls (NAC). In addition, they presented with more
      psychiatric comorbidity, lifetime numbers of trauma, recent psychotropic use and
      side effects. Increased medical comorbidity, health service utilization, as well
      as reduced work productivity were also found, particularly among SAD
      participants. SSAD participants were comparable to SAD participants for most of
      the measures with a few exceptions, mainly less psychiatric comorbidity, less
      medication use for panic attack and social fear, and fewer visits to the health
      professionals. In conclusion, SAD was highly prevalent among callers to the ADAA.
      SAD participants were particularly impaired and tended to use the health care
      system extensively. Although SSAD participants were less impaired than those with
      SAD, they were disadvantaged in many ways. Early diagnosis and better treatment
      are urged for reducing costs and improving life. An organization such as ADAA can
      play a vital role in bringing this about.

PMID- 15484223
TI  - Simultaneous analysis of piperacillin and tazobactam in rabbits: application to
      pharmacokinetic study.
AB  - A simple and rapid assay is developed for the simultaneous analysis of
      piperacillin and tazobactam in rabbit serum and tissue cage fluid (TCF). To
      eliminate endogenous interferences, a wavelength switch technique was applied, in
      which the programmable UV detector changed the monitoring wavelength from 218 to
      254 nm at 10 min. After liquid-liquid extraction, sample analyses were performed
      on a C(18) column by gradient elution; the mobile phase consisted of acetonitrile
      and phosphate buffer (0.014 m, pH 2.4). Owing to the limited amount of rabbit TCF
      available, a cross-validation of a proxy matrix was evaluated. The relative
      standard deviation of the between- and within-batch precision of both compounds
      was less than 5.1%; the relative error of the between- and within-batch accuracy
      was less than 7.3%. The recoveries of both compounds in serum and TCF were larger
      than 80%. This assay was successfully applied to simultaneously analyze
      piperacillin and tazobactam in rabbit serum and TCF samples.

PMID- 15484224
TI  - Determination of zolmitriptan enantiomers in rat liver microsomes by chiral high
      performance liquid chromatography with fl uorescence detection.
AB  - A selective chiral high performance liquid chromatographic method was developed
      and validated to separate and quantify the enantiomers of a new potent selective
      5-HT(1B/1D) receptor partial agonist, S-zolmitriptan, and its antipode in rat
      liver microsomes induced with beta-naphtho flavone. S- and R-zolmitriptan were
      extracted from rat hepatic microsomal incubates with chloroform/isopropanol
      (75:25, v/v), and were separated on a narrow-bore enantioselective normal phase
      Chiralpak AD-H column (250 x 0.46 mm) with hexane-isopropanol-triethylamine
      (72/28/0.25, v/v/v) as mobile phase and fluorescence detection with emission at
      350 nm and excitation at 291 nm. The calibration curves were linear for R- and S
      zolmitriptan concentration over the range 0.1-5.0 microg/mL (r = 0.9996 and
      0.9999), and the limits of quantitation were 0.1 microg/mL. The metabolism and
      interaction of the enantiomers of zolmitriptan in treated hepatic microsomes were
      investigated using chiral HPLC. There was significant difference between the
      disposition of the S- and R-zolmitriptan when racemic zolmitriptan or single
      enantiomers of zolmitriptan were incubated for 5, 10 and 20 min, suggesting that
      the metabolism of zolmitriptan in rat liver microsomes is enantioselective. In
      addition, there was also a significant difference between the IC(50) of R- to S
      zolmitriptan and S- to R-zolmitriptan (IC(50S/R)/IC(50R/S) = 45.2). This
      indicated that the disposition process favored the S-form of zolmitriptan.

PMID- 15484225
TI  - Validation study of a method for assaying DE-310, a macromolecular carrier
      conjugate containing an anti-tumor camptothecin derivative, and the free drug in
      tumor tissue by high performance liquid chromatography/atmospheric pressure
      chemical ionization tandem mass spectrometry.
AB  - DE-310 is a macromolecular carrier conjugate containing an anti-tumor
      camptothecin derivative, DX-8951, which is conjugated to a water-soluble polymer
      via a peptide spacer. Assay methods have been developed for the determination of
      a polymer-bonded DX-8951 conjugate, DX-8951, and Glycyl-DX-8951 concentrations in
      murine Meth A tumor tissue. Free DX-8951 and Glycyl-DX-8951 were extracted from
      tumor tissue homogenates by protein precipitation and analyzed by LC/MS/MS
      (method I). Conjugated DX-8951 was isolated by solid-phase extraction after
      digestion with a thermolysin. The productive phenylalanyl-glycyl-DX-8951 was
      analyzed by LC/MS/MS (method II). The lower limits of quantitation of DX-8951,
      Glycyl-DX-8951, and conjugated DX-8951 were 1.36, 1.34 and 73.7 ng/g (as DX-8951
      equivalent). These two methods showed satisfactory sensitivity, precision and
      accuracy. To study the pharmacokinetics of DE-310, it would be of great help to
      assay the polymer-bonded DX-8951 and its released drugs in tumor tissue.

PMID- 15484226
TI  - High-performance liquid chromatographic method for simultaneous determination of
      sophoridine and matrine in rat plasma.
AB  - A high-performance liquid chromatographic (HPLC) method is described for the
      simultaneous determination of sophoridine and matrine in rat plasma. Sophoridine
      and matrine in the resulting supernatant of the plasma deproteinized with
      acetonitrile containing an internal standard (acetanilide) were directly
      determined by reversed-phase HPLC and ultraviolet detection. The result of limits
      of quantitation for matrine and sophoridine were 200 and 350 ng/mL in plasma,
      respectively, and recovery of both analytes was greater than 98%. The assay was
      linear from 250 to 4000 ng/mL for matrine and from 500 to 8000 ng/mL for
      sophoridine. Variation over the range of the standard curve was less than 15%.
      The method was used to determine the concentration-time profiles of matrine and
      sophoridine in the plasma following oral administration of Kexieling tablets,
      which is one of the preparations of Kudouzi at a dose equivalent to 30 and 60
      mg/kg of matrine and sophoridine, respectively.

PMID- 15484227
TI  - The role of salivary peptides in dental caries.
AB  - Dental caries is a complex disease, characterized by demineralization of tooth
      structure. With a protective role, several salivary phosphopeptides appear to be
      involved in remineralization processes, delaying the loss of tooth structure. In
      this work we have correlated peptide saliva composition with dental caries
      susceptibility through the analysis of saliva and hydroxyapatite-adsorbed
      salivary peptides samples. Saliva samples were obtained from two groups, a caries
      free and a cariessusceptible group, and were analysed using HPLC-MS and a
      sequential extraction with 6 m of guanidine followed by tri fluoroacetate. Data
      analysis has allowed us to verify a strong correlation between large amounts
      phosphopeptides (PRP1/3, histatin 1 and statherin), and the absence of dental
      caries, which reinforces the importance of these peptides in the maintenance of
      tooth integrity. In addition, in the caries-susceptible group a high number of
      peptide fragments was observed, suggesting a high proteolytic activity.

PMID- 15484228
TI  - HPLC determination and pharmacokinetic studies of salvianolic acid B in rat
      plasma after oral administration of Radix Salviae Miltiorrhizae extract.
AB  - A precise and reproducible HPLC method has been established and validated for
      determination of salvianolic acid B (SalB) in rat plasma after oral
      administration of Radix Salviae Miltiorrhizae extract. Liquid-liquid extraction
      was adopted for the sample preparation. Separation was accomplished on a C(18)
      column with a linear gradient elution consisting of acetonitrile and aqueous
      phosphoric acid. Ultraviolet detection was at 280 nm. The method was validated
      over the concentration range 10.8-259.4 microg/mL using 1 mL of plasma. The assay
      was linear over this concentration range with a coefficient of variation less
      than 7%. The extraction recovery of SalB was within the range 71-83% with RSD
      11%. The mean recovery of the internal standard was 84% (n = 6) with RSD of 5.6%.
      This method is suitable to determine SalB in plasma and to investigate the
      pharmacokinetics of SalB.

PMID- 15484229
TI  - An IkappaB-beta COOH terminal region protein is essential for the proliferation
      of CHO cells under acidic stress.
AB  - CHO-K1 cells were able to proliferate and maintain pHi homeostasis at pH 6.3. A
      novel acidic sensitive mutant, AS-5B, which proliferated at pH 7.4 but failed to
      either proliferate or maintain pHi homeostasis at pH 6.3, was derived from CHO-K1
      using a replica method. The acidic-sensitivity of AS-5B was not due to
      deficiencies in sodium proton exchangers, HCO3- (co)transporters or H+-ATPases. A
      cDNA clone encoding a COOH terminal region of IkappaB-beta conferred partial
      acidic-resistance on AS-5B, and the encoded protein was present in CHO-K1, but
      was nearly absent from AS-5B. Our data demonstrated that the expression of this
      small protein was essential for the proliferation of CHO cells under acidic
      stress.

PMID- 15484230
TI  - HPLC determination of four active saponins from Panax notoginseng in rat serum
      and its application to pharmacokinetic studies.
AB  - Four main active saponins (ginsenosides Rg1, Rb1, Rd and notoginsenoside R1) in
      Panax notoginseng in rat serum after oral and intravenous administration of total
      saponins of P. notoginseng (PNS) to rats were determined using a simple and
      sensitive high-performance chromatographic method. The serum samples were
      pretreated with solid-phase extraction before analysis. The calibration curves
      for the four saponins were linear in the given concentration ranges. The intra
      day and inter-day assay coefficients in serum were less than 10.0% and the
      recoveries of the method were higher than 80.0% in the high, middle and low
      concentrations. This method was applied to study the pharmacokinetics following
      oral and intravenous administration of PNS.

PMID- 15484231
TI  - Thermodynamically controlled self-assembly of two-dimensional oxide
      nanostructures.

PMID- 15484233
TI  - Gas-phase reactions of the [(PHOX)IrL(2)](+) ion olefin-hydrogenation catalyst
      support an Ir(I)/Ir(III) cycle.

PMID- 15484234
TI  - Expanding the LnZ(3)/alkali-metal reduction system to organometallic and
      heteroleptic precursors: formation of dinitrogen derivatives of lanthanum.

PMID- 15484235
TI  - Biotransformations in low-boiling hydrofluorocarbon solvents.

PMID- 15484236
TI  - Methacrylate polymerization using a dinuclear zirconocene initiator: a new
      approach for the controlled synthesis of methacrylate polymers.

PMID- 15484237
TI  - Integrating single-wall carbon nanotubes into donor-acceptor nanohybrids.

PMID- 15484238
TI  - Ansa-cycloheptatrienyl-cyclopentadienyl complexes.

PMID- 15484239
TI  - Germacarboxylic acid: an organic-acid analogue based on a heavier group 14
      element.

PMID- 15484240
TI  - Ca[Si(2)O(2)N(2)]--a novel layer silicate.

PMID- 15484241
TI  - Hydroamination/cyclization of aminoalkenes using cationic zirconocene and
      titanocene catalysts.

PMID- 15484242
TI  - Hemibuckminsterfullerene C(30)H(12): X-ray crystal structures of the parent
      hydrocarbon and of the two-dimensional organometallic network
      [[Rh(2)(O(2)CCF(3))(4)](3)x(C(30)H(12))].

PMID- 15484243
TI  - Rationalization of supramolecular chirality in a bisporphyrin system.

PMID- 15484244
TI  - Mono- and multidecker sandwich-like complexes of the tetraazacyclobutadiene
      aromatic ring.

PMID- 15484245
TI  - The lone-pair cation I(5+) in a hexagonal tungsten oxide-like framework:
      synthesis, structure, and second-harmonic generating properties of
      Cs(2)I(4)O(11).

PMID- 15484246
TI  - Supramolecular assemblies of starlike and V-shaped PB-PEO amphiphiles.

PMID- 15484247
TI  - Cucurbit[8]uril-mediated redox-controlled self-assembly of viologen-containing
      dendrimers.

PMID- 15484248
TI  - Control of nanoparticle assembly by using DNA-modified diatom templates.

PMID- 15484249
TI  - Reversibly addressing an allosteric catalyst in situ: catalytic molecular
      tweezers.

PMID- 15484250
TI  - Highly enantioselective direct organocatalytic alpha-chlorination of ketones.

PMID- 15484254
TI  - Alan R. Fersht receives Bader Award / Corey Award to David W. C. MacMillan /
      Breslow Award to Peter B. Dervan.

PMID- 15484251
TI  - Diastereoselective synthesis of cycloheptadienol derivatives by a formal [5+2]
      carbocyclization reaction of alpha,beta,gamma,delta-diunsaturated
      (methoxy)carbene complexes with methyl ketone lithium enolates.

PMID- 15484255
TI  - Electrophilic double-sandwiches formed by interaction of [Cp(2)Fe] and [Cp(2)Ni]
      with the tridentate lewis acid [(o-C(6)F(4)Hg)(3)].

PMID- 15484256
TI  - Rhodium silyl boryl hydride complexes: comparison of bonding and the rates of
      elimination of borane, silane, and dihydrogen.

PMID- 15484257
TI  - Diversity of G proteins in Lepidopteran cell lines: partial sequences of six G
      protein alpha subunits.
AB  - The aim of this work was to sample the diversity of G protein alpha subunits in
      lepidopteran insect cell lines. Here we report the amplification by degenerate
      PCR of partial sequences representing six G protein alpha subunits from three
      different lepidopteran insect cell lines. Sequence comparisons with known G
      protein alpha subunits indicate that the Sf9, Ld and High Five cell lines each
      contain (at least) one Galpha(q)-like and one Galpha(i)-like Galpha subunit. All
      six PCR products are unique at the nucleotide level, but the translation products
      of the three Galpha q-like partial clones (Sf9-Galpha 1, Ld-Galpha 1, and Hi5
      Galpha 1) are identical, as are the translation products of the three Galpha i
      like partial clones (Sf9-Galpha 2, Ld-Galpha 2, and Hi5-Galpha 2). Both the
      Galpha(q)-like and Galpha(i)-like translation products are identical to known
      Galpha subunits from other Lepidoptera, are highly similar (88-98%) to Galpha
      subunits from other invertebrates including mosquitoes, fruit flies, lobsters,
      crabs, and snails, and are also highly similar (88-90%) to known mammalian Galpha
      subunits. Identification of G protein alpha subunits in lepidopteran cell lines
      will assist in host cell line selection when insect cell lines are used for the
      pharmacological analysis of human GPCRs.

PMID- 15484258
TI  - Effect of the hydrophilic nanofiller loading on the mechanical properties and the
      microtensile bond strength of an ethanol-based one-bottle dentin adhesive.
AB  - This study evaluated the hypothesis that if hydrophilic nanofillers were
      dispersed evenly within the adhesive layer under moist conditions, adding them to
      a one-bottle dentin adhesive might improve the mechanical properties of the
      adhesive layer, and accordingly increase the bond strength. The flexural strength
      (FS), the degree of conversion (DC), and the microtensile bond strength (MTBS) to
      the dentin of four experimental ethanol-based one-bottle dentin adhesives
      containing 0, 0.5, 1.0, and 3.0 wt % of 12-nm hydrophilic fumed silica were
      evaluated, and the distribution of the nanofillers were compared using
      transmission electron microscopy (TEM). Although the nanofiller content did not
      affect the DC, the FS tended to increase with increasing nanofiller content. The
      MTBS appeared to increase when up to 1.0 wt % of the nanofillers were added, but
      they were statistically not significant. However, when 3.0 wt % of the
      nanofillers were added, the MTBS decreased significantly comparing to the
      adhesive containing 0.5 wt % nanofillers (p < 0.05). The TEM image suggested that
      if the nanofillers within the adhesive were 3.0 wt % and applied to a wet dentin
      surface, they aggregated easily into large clusters and would decrease the MTBS.

PMID- 15484259
TI  - Comparative larvicidal toxicities of three ecdysone agonists on the mosquitoes
      Aedes aegypti, Culex quinquefasciatus, and Anopheles gambiae.
AB  - Ecdysone agonists are hormonally active insect growth regulators that disrupt
      development of pest insects and have potential for development as insecticides.
      Their effects have been particularly well-studied in Lepidoptera and Coleoptera,
      but significantly less is known about their effects on dipterans, particularly
      aquatic species. The potency of three ecdysone agonists on larvae of 3 mosquito
      species, Aedes aegypti, Anopheles gambiae, and Culex quinquefasciatus, was
      examined. Anopheles gambiae was the most susceptible species and Ae. aegypti was
      the most resistant species to the effects of the three compounds tested. Potency,
      in descending order, was RH-2485 > RH-5992 > RH-5849. Dose-response relationships
      were determined for the three agonists; RH-2485 was found to be the most
      effective endocrine disruptor against all three species. The observed biological
      effects of these compounds were similar to those reported for other insects, and
      mosquitoes initiated molting and apolysis but did not complete a molt. In some
      cases, mosquito larvae synthesized a new cuticle that appeared to be normally
      sclerotized but the larvae failed to ecdyse and shed the exuvium. These compounds
      may prove to be valuable insect growth regulators for control of mosquitoes to
      decrease the frequency of pathogen transmission to humans. Prospects for using
      these compounds to control mosquitoes in the field are discussed, along with
      possible impacts on non-target arthropods in mosquito habitats.

PMID- 15484260
TI  - The angiotensin converting enzyme inhibitor captopril reduces oviposition and
      ecdysteroid levels in Lepidoptera.
AB  - The role of angiotensin converting enzyme (ACE, peptidyl dipeptidase A) in
      metamorphic- and reproductive-related events in the Egyptian cotton leafworm,
      Spodoptera littoralis (Lepidoptera, Noctuidae) was studied by using the selective
      ACE inhibitor captopril. Although oral administration of captopril had no effect
      on larval growth, topical administration to new pupae resulted in a large
      decrease of successful adult formation. Oviposition and overall appearance of
      adults emerging from treated larvae did not differ significantly from those
      emerging from non-treated larvae. In contrast, topical or oral administration of
      captopril to newly emerged adults caused a reduction in oviposition. By
      evaluating the effect of captopril on ecdysteroid titers and trypsin activity, we
      revealed an additional physiological role for ACE. Captopril exerted an
      inhibitory effect on ecdysteroid levels in female but not in male adults. Larvae
      fed a diet containing captopril exhibited increased trypsin activity. A similar
      captopril-induced increase in trypsin activity was observed in female adults. In
      male adults, however, captopril elicited reduced levels of trypsin activity. Our
      results suggest that captopril downregulates oviposition by two independent
      pathways, one through ecdysteroid biosynthesis regulation, and the other through
      regulation of trypsin activity. Apparently, fecundity is influenced by a complex
      interaction of ACE, trypsin activity, and ecdysteroid levels.

PMID- 15484261
TI  - Apolipophorin-III-like protein expressed in the antenna of the red imported fire
      ant, Solenopsis invicta Buren (Hymenoptera: Formicidae).
AB  - Antennal proteins of the male fire ant (Solenopsis invicta) were analyzed by two
      dimensional gel electrophoresis, with the objective of identifying pheromone
      binding proteins, which have not previously been found in ant antennae. The major
      low-molecular weight protein found in the male fire ant antenna was subjected to
      Edman degradation to determine the N-terminal amino acid sequence. Degenerate PCR
      primers based on this sequence were used to obtain a cDNA sequence corresponding
      to the full-length protein sequence. In-gel trypsin digestion followed by MALDI
      TOF mass spectrometry and HPLC-ESI/MS/MS demonstrated that the protein gel spot
      contained only the protein corresponding to the cDNA sequence obtained by PCR.
      The sequence is similar to apolipophorin-III, an exchangeable lipid-binding
      protein. Fire ant apolipophorin-III is expressed in the antenna as well as the
      head, thorax and abdomen.

PMID- 15484262
TI  - Rhodnius prolixus Malpighian tubule's aquaporin expression is modulated by 5
      hydroxytryptamine.
AB  - The purpose of the present study was to detect the presence of an aquaporin-like
      water channel, a member of the major intrinsic protein (MIP) family, in the
      Malpighian tubule (MT) of the hematophagous insect Rhodnius prolixus, which
      excrete a large bulk of fluid after a massive blood meal, and its possible
      regulation by 5-hydroxytryptamine (5-HT). Reverse transcription polymerase chain
      reaction (RT-PCR) and Southern blots of cDNA was obtained from adult R. prolixus
      MT poly (A)+ RNA. Employing degenerate primers corresponding to the NPA (amino
      acid sequence motifs repeats Asn-Pro-Ala) highly conserved domain of amino acids
      sequences of all members of the MIP gene family, we were able to identify a 365
      base pair PCR product. The R. prolixus MT mRNA expression of this water
      transporter is increased in the animal after blood meal and in tubules treated
      with 5-hydroxytryptamine or cAMP. The up-regulated expression of MT MIP mRNA
      after a blood meal is probably due to the action of 5-hydroxytryptamine via a
      cyclic AMP dependent pathway.

PMID- 15484263
TI  - Evidence of rotavirus AU32 like G9 strains from nontypeable fecal specimens of
      Indian children hospitalized during 1993-1994.
AB  - Serotyping of 432 rotavirus positive fecal specimens collected from hospitalized
      children during 1990-1997 was carried out at National Institute of Virology
      (NIV), Pune, India, using monoclonal antibodies (MAbs) directed against VP7
      determinant of serotypes G1-G4, G6, G8, and G10. However, significant number of
      specimens, that is, 47.92% remained nontypeable. The aim of the present study was
      to culture adapt the nontypeable specimens and to characterize them further.
      Since the fecal specimens were not tested by MAb to G9 serotype, which has
      emerged as an important serotype infecting humans recently, presence of G9
      serotype was expected in nontypeable specimens. Therefore, we selected specimens
      from those children, who showed higher neutralizing antibody (NAb) titer in their
      convalescent serum samples to G9 serotype than their mothers. Out of six isolates
      having long electropherotype, five isolates showed subgroup II, and one showed
      subgroup I, II. The isolates were confirmed as G9 by MAb based ELISA,
      neutralization assay, and PCR. The G9 specific nested PCR products of four
      isolates showed 96-99% identities to AU32 G9 strain reported from Japan. P type
      of four isolates was determined as P8. Besides isolates, four additional
      nontypeable fecal specimens were confirmed as G9 by MAb based ELISA. Thus, 10
      (28.57%) out of 35 nontypeable specimens were identified as rotavirus serotype
      G9. The results indicate that serotype G9 may represent significant proportion of
      specimens, which were previously nontypeable.

PMID- 15484264
TI  - Rapid detection of varicella-zoster virus infection by a loop-mediated isothermal
      amplification method.
AB  - The reliability of varicella-zoster virus (VZV) loop-mediated isothermal
      amplification (LAMP) was evaluated for rapid diagnosis of viral infection. VZV
      specific primers only amplified VZV DNA; no LAMP products were observed in
      reactions performed with other viral DNA templates. The specificity of this
      method was confirmed by two independent determinations, agarose gel
      electrophoresis and a turbidity assay. The sensitivity of VZV LAMP, determined by
      agarose gel electrophoresis, were 500 copies/tube. Detection using the turbidity
      assay, however, gave a sensitivity of 1,000 copies/tube. After these initial
      validation studies, reliability of VZV LAMP was evaluated for the detection of
      viral DNA in clinical specimens. Thirty-two swab samples collected from patients
      with vesicular skin eruptions were tested for VZV DNA. VZV was confirmed in
      sample numbers 10-32 by VZV real-time PCR, a previously established technique.
      VZV LAMP products were detected using turbidity from samples 13 to 32
      (sensitivity; 87.0%, specificity; 100%, positive predictive value; 100%, negative
      predictive value; 75%). Although low levels of VZV DNA could be detected in the
      three samples exhibiting divergent results (samples numbers 10-12), no VZV LAMP
      product was detected in these samples, indicating a higher detection limit for
      this assay. Requirement of a DNA extraction step in the VZV LAMP method was
      examined in next experiment. The turbidity assay detected a VZV LAMP product in
      all of the 20 positive swab samples (samples numbers 13-32), regardless of DNA
      extraction.

PMID- 15484265
TI  - Change in hepatitis C virus genotype in injecting drug users.
AB  - Six major genotypes of the hepatitis C virus (HCV) have been described; it is
      assumed to be uncommon for genotypes to change in chronically infected
      individuals. Venous blood samples obtained from Vietnamese-Australian injecting
      drug users who participated in successive studies conducted in Melbourne,
      Australia, were genotyped using the Bayer line probe assay and genotype confirmed
      by sequencing whenever possible. Three changes of HCV genotype were observed, and
      one infection in an individual not exposed previously. The rate of change of
      genotype was 3 in 11.4 person-years (py), or 26.4 per 100 py (95% CI: 8.5, 81.6).
      Traditionally-calculated HCV incidence was 1 in 4.3 py, or 23.3 per 100 py (95%
      CI: 3.3, 165.1). These data imply that HCV genotype change in injecting drug
      users occurs at least as frequently as infections in naive individuals, and that
      traditionally-calculated HCV incidence rates represent a minority of actual HCV
      transmission among practicing injecting drug users.

PMID- 15484266
TI  - Human endothelial cell activation and apoptosis induced by enterovirus 71
      infection.
AB  - Enterovirus 71 (EV71), a neurotropic virus, its infection is transmitted mainly
      by the oral-fecal route. However, it is unclear how EV71 is disseminated/spread
      from initial replication sites to the central nervous system. Since endothelial
      cells form the interface between blood and tissues throughout the body, it is
      likely that EV71 can infect and then exit endothelial cells to establish
      infection. In this study, human endothelial cells were examined for
      susceptibility to EV71 infection using human microvascular endothelial cell line
      (HMEC-1 cell). Immunofluorescence assay confirmed EV71 infection of HMEC-1.
      Viable viruses were cultured from both the culture supernatant and the cell
      lysate. Live but not UV-inactivated EV71 induced HMEC-1 to secrete IL-6,
      macrophage migration inhibition factor, and macrophage chemo-attractant protein
      1, and to express toll-like receptor 4. In addition, EV71 decreased the viability
      and increased the apoptosis of HMEC-1 cells after 36-48 hr of infection. These
      results demonstrate that EV71 is able to infect, activate, and induce apoptosis
      of endothelial cells, which may play a role in the pathogenesis of EV71
      infection.

PMID- 15484267
TI  - High prevalence of mixed genotype infections in hepatitis B virus infected
      intravenous drug users.
AB  - The clinical relevance of hepatitis B virus (HBV) genotypes has been documented;
      however, the prevalence of mixed HBV genotype infections in at-risk groups
      remains controversial. The HBV genotypes were determined in 325 HBV-infected
      intravenous drug users (IVDU) who were at a greater risk of multiple exposures to
      different HBV genotypes by using a newly developed line probe assay. The
      distribution of HBV genotype was as follows: genotype A alone in 2 (0.6%);
      genotype B alone in 256 (78.8%); genotype C alone in 10 (3.1%); mixed genotype A
      and B in 18 (5.5%); genotype B and C in 30 (9.2%); genotype B and D in 1 (0.3%);
      genotype A and C in 1 (0.3%); and mixed infections of genotype A, B, and C in 3
      (0.9%). Clonal analysis confirmed further the existence of mixed genotype
      infection and recombination between different genotypes. Compared with our
      previous data, the line probe assay seemed more sensitive than polymerase chain
      reaction (PCR)-restriction fragment length polymorphism (RFLP) assay in
      identifying HBV genotype (98.8% vs. 65.0%) and detecting mixed genotype
      infections (16.3% vs. 0%). In conclusion, the prevalence of mixed HBV infections
      is substantially higher in IVDU in endemic areas, and the line probe assay is a
      useful method for rapid genotyping of HBV, with particular reference to the
      detection of mixed genotype infections.

PMID- 15484268
TI  - Effects of mutations in an HIV-1 gag gene containing a 107-codon tandem repeat in
      the matrix region on assembly and processing of the protein product.
AB  - It has been demonstrated previously that a human immunodeficiency virus (HIV)
      type 1 Gag mutant (MA2) with a tandem repeat of 107-matrix codons in the matrix
      domain could direct virus particle assembly and budding [Wang et al. (2000c): J
      Med Virol 61:423-432]. Since the regions involved functionally in HIV Gag
      assembly and transport have been mapped to the matrix domain, it was interesting
      to test the effects of the duplicated matrix-coding sequence on Gag assembly,
      transport, and virus processing of some assembly-defective HIV matrix mutants. In
      this study, a number of HIV matrix mutations were introduced into either the
      proximal or distal copy of the duplicated matrix-coding sequence. Assembly,
      release, processing, and subcellular localization of the Gag mutants were
      analyzed by transient expression in 293T cells. The result indicates that the
      budding defect of HIV matrix mutants could be moderately or significantly
      reversed when the additional 107-matrix codons were present; however, these
      matrix double mutations affected significantly the virus particle processing.
      Mislocalized matrix mutants could also be redistributed to a certain degree in
      the presence of the duplicated matrix copy. Although the subcellular distribution
      patterns of the matrix mutants did not correlate completely with the budding
      efficiency, the data suggest that the budding defect caused by the matrix
      mutations could be masked to some extent by the duplicated matrix coding
      sequence.

PMID- 15484269
TI  - Investigation of simian virus 40 large T antigen in 18 autopsied malignant
      mesothelioma patients in Japan.
AB  - It has been reported that Simian virus 40 (SV40) is linked to human beings by
      inoculation of contaminated poliovaccines and may have a role in the etiology of
      malignant mesothelioma. However, there have been no reports describing the
      relationship between SV40 and malignant mesothelioma in Japan. A study was
      undertaken to investigate whether SV40 was related to patients of malignant
      mesothelioma in Japan by the polymerase chain reaction (PCR) assay, DNA sequence
      analysis, and immunohistochemical methods. Paraffin-embedded samples of the 18
      autopsied patients with pleural malignant mesothelioma were collected from five
      hospitals in Japan. After isolation of DNA from paraffin blocks, PCR analyses
      followed by sequencing were performed using three different sets of primers for
      detection of SV40 large T antigen (TAg) gene. All 18 malignant mesothelioma
      samples were also immunohistochemically evaluated for expression of SV40 TAg
      protein with two different anti-SV40 TAg antibodies. SV40 TAg genome was detected
      in eight malignant mesothelioma cases. Only one of three primer pairs
      successfully amplified SV40 genome in the samples, whereas all pairs yielded a
      PCR product in the controls, suggesting a low content of virus DNA. No
      immunopositive staining for SV40 TAg was found in any of the samples. This study
      shows that SV40 genome was present in a subset of Japanese malignant mesothelioma
      patients who were unlikely to have received a contaminated polio vaccine based on
      their age.

PMID- 15484270
TI  - Prevalence of HIV-1 non-B subtypes, syphilis, HTLV, and hepatitis B and C viruses
      among immigrant sex workers in Madrid, Spain.
AB  - Sexually transmitted disease (STD) remains a major public health challenge in
      developed countries, exacerbated by the advent of the HIV epidemic. The
      objectives of this study were to assess the prevalence of serological markers of
      syphilis, HIV-1/2, HTLV-I/II, HBV, and HCV infections among immigrant sex workers
      in Madrid, Spain and to characterize the HIV-1 variants in seropositive
      individuals. Sera from 762 immigrant commercial sex workers (75.3% from sub
      Saharan Africa, 18.2% from South America, and 6.4% from Eastern Europe) were
      collected between 1998 and 2003 in Madrid and examined. Antibody detection was
      performed by screening assays (RPR, ELISAs) and confirmed by FTA-Abs, LIAs and
      Western-blot tests. HIV-1 subtyping was carried out by phylogenetic analyses of
      the protease and envelope genes. Antibodies to HIV-1 were found in 5.2%, while
      3.5% tested positive for HBsAg, 3% for syphilis antibodies, 0.8% for HCV
      antibodies, and 0.2% for HTLV-I antibodies. None were reactive for HIV-2 or HTLV
      II antibodies. HIV-1 seroprevalence among Africans and Ecuadorians was 4.5 and
      10.9%, respectively. All HIV-1 seropositive Ecuadorians were transsexual men, and
      28.6% had active syphilis infection. Up to 80% of HIV-1 positive specimens were
      characterized as non-B subtypes, with subtypes G, A, and G/A recombinants being
      the most frequent among African individuals. In contrast, South Americans with
      HIV-1 infection carried exclusively subtype B variants. A relatively high
      proportion of immigrant sex workers in Madrid were infected with HIV-1 and
      syphilis, whereas infections with hepatitis viruses or HTLV were uncommon.

PMID- 15484271
TI  - Culture adaptation of serotype G6 human rotavirus strains from hospitalized
      diarrhea patients in India.
AB  - During serotyping of fecal specimens positive for rotavirus from hospitalized
      diarrhea patients in Pune, India, about 10% showed multireactivity in enzyme
      immunoassay with monoclonal antibodies specific for serotypes G1-4, 6, 8, and 10.
      In order to characterize some of these, three fecal specimens from children and
      one from adult were culture adapted. All the isolates showed long RNA pattern,
      but three out of four isolates belonged to subgroup I and II and one, to subgroup
      I. The isolates were confirmed as G6 by neutralization assay and polymerase chain
      reaction. Nucleotide sequences of cDNA derived from the gene encoding the outer
      capsid protein, VP7 of two strains indicated >94% identity with G6, the serotype,
      generally associated with cattle. The isolates were more close to G6 RF strain,
      which is a bovine rotavirus, reported from France. This is a first report of
      isolation of bovine serotype, G6 from children as well as adults from India.

PMID- 15484272
TI  - Phylogenetic analysis of a human group B rotavirus WH-1 detected in China in
      2002.
AB  - A human group B rotavirus strain WH-1 was detected in an adult sporadic case of
      diarrhea in Wuhan, China in 2002. In this study, the gene sequences of WH-1 were
      determined in order to examine the phylogenetic relatedness to other human group
      B rotaviruses found previously in China (ADRV, in 1982), India (CAL-1, in 1998),
      and Bangladesh (Bang373, in 2000), as well as animal viruses, and to estimate the
      mutation rate of group B rotavirus. VP7 (major outer capsid protein) gene of WH-1
      showed extremely high sequence identity (98.6%) to ADRV and showed relatively
      high sequence identities to CAL-1 (92.5%) and Bang373 (92.4%). In contrast,
      identities to animal (bovine and murine) group B rotaviruses were considerably
      lower (61-64%). Other gene segments of WH-1 encoding VP2, VP4, VP6, NSP1-NSP3,
      and NSP5 also showed high sequence identities to ADRV genes (98-99%), which were
      generally higher than those to CAL-1 genes and Bang373 genes (90-95%). However,
      amino acid sequence identities between WH-1 and ADRV were almost the same (VP2,
      VP6, and NSP3), or lower (NSP2) than those between WH-1 and CAL-1 (or Bang373).
      Since rates of synonymous substitution and transition between WH-1 and ADRV were
      similar for all the segments analyzed, genetic evolution was considered to have
      occurred neutrally and at a similar speed in most of the RNA segments. Based on
      the sequence divergence between WH-1 and ADRV, the mutation rate in natural
      condition of human group B rotavirus was estimated as 7.9 x 10(-4)
      substitution/site per year. The frequency of synonymous substitution between ADRV
      and Bang373 was 5.7 times higher than that between ADRV and WH-1, suggesting that
      the group B rotaviruses of Indian-Bangladeshi lineage diverged from that of
      Chinese lineage several decades ago.

PMID- 15484273
TI  - Quantitation of Epstein-Barr virus mRNA using reverse transcription and real-time
      PCR.
AB  - Monitoring of Epstein-Barr virus (EBV) infection and reactivation in
      immunocompromized patients (e.g., after organ or bone-marrow transplantation) is
      based mainly on serological assays and detection of viral DNA. For further
      characterization of virus reactivation and monitoring of viral transcription we
      established real-time RT-PCR assays using TaqMan technology to sensitively
      quantify viral transcripts expressed at different times of the lytic cycle: for
      BZLF1, an immediate early transactivator initiating the transition from latency
      to lytic replication, for the DNA-polymerase BALF5 and for the major viral
      glycoprotein gp350/220 (BLLF1). RNA-isolation was optimized to eliminate
      contaminating DNA. Preparations were shown to be virtually DNA-free for up to
      10(6) copies of RNA. With our PCR systems, it is possible to detect 10 copies of
      DNA or 100 copies of RNA per reaction as shown with serial dilutions of DNA
      plasmids or in vitro transcribed RNA, respectively. This corresponds to a
      detection limit of 8 x 10(2) copies/10(6) peripheral blood mononuclear cells
      (PBMCs). Evaluation of this system showed that even in healthy carriers
      borderline levels of BLLF1 mRNA were sometimes detectable. In patients with acute
      infectious mononucleosis (IM) viral transcripts were regularly found in varying
      concentrations. Extremely high levels of all three mRNA species could be seen in
      a patient after bone-marrow transplantation monitored during an episode of
      lymphoproliferation which regressed during treatment with acyclovir and
      transfusion of donor T-cells. This sensitive and reproducible method to detect
      and quantify different transcripts of EBV can be used to closely monitor
      reactivation of EBV, e.g., in immunocompromized patients.

PMID- 15484274
TI  - E. coli-expressed recombinant norovirus capsid proteins maintain authentic
      antigenicity and receptor binding capability.
AB  - The baculovirus expression system has been widely used to produce the capsid
      proteins of Norovirus (NV) and the proteins form virus-like particles (VLPs) that
      are useful in many studies, such as immunology, diagnosis, and host-receptor
      interaction. We report here the application of the E. coli expression system in
      the production of recombinant NV capsid proteins. In a direct comparison of a
      previous well-characterized NV strain (VA387), we have demonstrated that the E.
      coli-expressed capsid proteins maintain the same antigenicity and receptor
      binding specificity as that of the baculovirus-expressed capsid, although the E.
      coli-expressed VA387 proteins did not form VLPs. Using the E. coli-expression
      system, we characterized the receptor-binding patterns of three additional NV
      strains (OIF1998, Parris Island and VA115), in which OIF1998 binds to HBGA of
      nonsecretors but did not bind or binds weakly to the HBGA of secretors, as seen
      in strain VA207. Parris Island binds to HBGA of types A and B but not type O
      secretors and nonsecretors. VA115 did not show specific binding to any A, B, O
      secretor nor nonsecretor, which is also observed when the capsid protein of this
      strain was expressed in baculovirus. Our data indicate that VLP formation is not
      required for receptor binding, and that the bacteria expression system offers a
      simple alternative for large production of NV capsid protein for various research
      purposes, particularly for strains generating low yields in the insect cells.

PMID- 15484275
TI  - Characterization of tick-borne encephalitis virus from Estonia.
AB  - Tick-borne encephalitis virus (TBEV) is a severe problem in Estonia. In the
      present article the first genetic analysis of Estonian TBEV strains is described.
      In total, seven TBEV strains were isolated from ticks (Ixodes ricinus and I.
      persulcaus), rodents (Apodemus agrarius and Cletrionomys glareolus), and serum
      from a tick-borne encephalitis (TBE) patient. The nucleic acid sequences of the
      viral genome encoding almost the complete E protein (nt 41-1250) and the 3'-NCR
      termini of the Estonian TBEV strains were determined by direct sequencing of RT
      PCR products. The results showed that all three known TBEV subtypes, Western TBEV
      (W-TBEV), Far-Eastern TBEV (FE-TBEV), and Siberian TBEV (S-TBEV), co-circulate in
      Estonia. The Estonian TBEV strains of the S-TBEV and W-TBEV subtypes clustered
      with the previously reported strains from Latvia and Lithuania. Within the FE
      TBEV subtype, however, the Estonian strain Est2546 clustered together with the
      strain Sofjin, originating from the Far-East of Russia, but not with the strain
      RK1424, isolated in the neighboring Latvia. This suggests a different
      evolutionary history for the Estonian and the Latvian strains in the FE-TBEV
      subtype. The Estonian TBEV strain (Est3535), which belonged to the S-TBEV
      subtype, had an organization of the 3'-NCR similar to that of strains from the
      Far-East of Russia (Irkutsk). The 3'-NCRs of Estonian strains of the W-TBEV
      subtype (Est3051, Est3053, Est3476, and Est3509) were very similar to those of
      the strain Ljubljana I from the Balkans. In the 3'-NCR sequence of the Estonian
      strain Est2546, which belonged to the FE-TBEV subtype, a deletion from position
      10461 to 10810 extending approximately 10 nucleotides into the core element, was
      detected.

PMID- 15484276
TI  - Improved diagnosis on a daily basis of enterovirus meningitis using a one-step
      real-time RT-PCR assay.
AB  - The detection of the enterovirus genome in cerebrospinal fluid (CSF) by PCR
      techniques has proved to be more sensitive than traditional cell culture for the
      diagnosis of enterovirus meningitis. However, PCR assays are time consuming and
      labor intensive, particularly if separate hybridization steps are used to confirm
      the specificity of positive findings. The aim of this study was to develop a one
      step real-time RT-PCR assay with LightCycler (LC) technology that was sensitive,
      rapid, and easy to perform in routine practice. The enterovirus detection limit
      was determined by testing 10-fold limiting dilution series of cell culture stocks
      with the echovirus 25 (E-25) prototype strain and with the third European Union
      Quality Control Concerted Action (EU-QCCA) enterovirus proficiency panel. A total
      of 100 CSF specimens were investigated in a comparative study. With the E-25
      strain, the detection limit of the real-time assay was 286 TCID50/ml (50% tissue
      culture infective dose). When samples of the EU-QCCA panel were tested, our assay
      gave identical results (detection limit down to 3.6 TCID50/ml) to those of the
      reference laboratory, which used one-step RT-PCR assay. When CSF specimens were
      tested, there was a correlation between the real-time assay and the conventional
      in-house assay in 96 of 100 CSFs tested. This one-step real-time assay allows
      rapid enterovirus detection in CSF since results are obtained in 3 hr as against
      36 hr with the "in-house" RT-PCR assay. This new assay is now being used in
      routine practice, and allows diagnosis on a daily basis.

PMID- 15484277
TI  - A highly hydrophobic domain within hypervariable region 1 may be related to the
      entry of hepatitis C virus into cultured human hepatoma cells.
AB  - Interaction of the envelope glycoprotein of hepatitis C virus (HCV) with a
      cellular receptor(s) is thought to be essential for the initial steps of HCV
      infection. However, the mechanisms of HCV infection remain unclear. The aim of
      the present study was to determine the features of HCV that enable efficient
      entry of the virus into human hepatocytes. Variations of hypervariable region 1
      (HVR1) sequences in HCV inocula and in infected human hepatoblastoma HepG2 cells
      were examined. Immunofluorescence of inoculated HepG2 cells with anti-HCV core
      antibodies demonstrated that HCV structural proteins were expressed in the
      cytoplasm, and their entry into HepG2 cells was confirmed. When the HVR1 amino
      acid sequences were compared, HVR1 quasispecies in the inoculated cells showed
      more uniformity than those of the inocula. Although there were no statistically
      significant differences between the two groups, hydrophobic residues were
      observed more frequently in the HVR1 amino acids from inoculated cells than in
      the HVR1 amino acids from the inocula. Results of hydropathy analysis revealed
      that highly hydrophobic domains exist in the middle of HVR1 in the inoculated
      cells in 7 of 10 patients. The results suggest that limited HCV populations are
      able to enter HepG2 cells and that the highly hydrophobic domain existing within
      the HVR1 may play an important role in the entry of HCV into cells.

PMID- 15484278
TI  - Prevalence of hepatitis E virus infection among hemodialysis patients in Japan:
      evidence for infection with a genotype 3 HEV by blood transfusion.
AB  - To investigate the prevalence of hepatitis E virus (HEV) infection among patients
      on maintenance hemodialysis, serum samples collected in January 2003 from 416
      patients who had been undergoing hemodialysis for 7.6 +/- 6.3 (mean +/- standard
      deviation) (range, 0.3-26.0) years in a dialysis unit in Japan and serum samples
      that had been collected from these patients at the start of hemodialysis were
      tested for IgG antibodies to HEV (anti-HEV IgG) by an "in-house" enzyme-linked
      immunosorbent assay (ELISA). Overall, 39 patients (9.4%) had anti-HEV IgG in
      January 2003, and included 35 patients (8.4%) who had already been positive for
      anti-HEV IgG at the start of hemodialysis and 4 patients (1%) who seroconverted
      after initiation of hemodialysis. Periodic serum samples that had been collected
      from the four seroconverted patients were tested for HEV antibodies and HEV RNA.
      The four patients became positive for anti-HEV IgG in 1979, 1980, 1988, or 2003,
      and continued to be seropositive until the end of the observation period.
      Although anti-HEV IgM was not detectable in the four patients, three were
      infected transiently with apparently Japanese indigenous HEV strains of genotype
      3. The patient who contracted HEV infection in 1979 had been transfused with 2 U
      of blood 21 days before the transient viremia: one of the two stored pilot serum
      samples had detectable HEV RNA with 100% identity to that recovered from the
      patient. Our study provides evidence of transfusion-transmitted HEV infection in
      Japan in 1979, and that the prevalence of de novo HEV infection during
      hemodialysis was low (1.1% or 4/374).

PMID- 15484279
TI  - Development and evaluation of a real-time nucleic acid sequence based
      amplification assay for rapid detection of influenza A.
AB  - The development and introduction of effective treatment for influenza A in the
      form of neuraminidase inhibitors have made the rapid diagnosis of infection
      important especially in high-risk populations. The aim of this study was to
      develop a real-time nucleic acid sequenced based amplification (NASBA) using a
      molecular beacon that could detect a wide range of influenza A subtypes and
      strains in a single reaction by targeting a conserved region of the influenza
      genome, and to evaluate its sensitivity and specificity against traditional
      laboratory techniques on a range of clinical samples usefulness during the
      2003/2004 influenza season. The results demonstrated the assay to be highly
      sensitive and specific, detecting <0.1 TCID50 of virus stock. Three hundred
      eighty-nine clinical samples were tested in total from two patient groups.
      Overall, the real-time NASBA assay detected 64% (66/103) more influenza positive
      samples than cell culture and direct immunofluorescence (IF) and, therefore, was
      shown to be more sensitive in detecting influenza A in a wide range of
      respiratory samples than traditional methods. In conclusion, the real-time
      influenza A assay demonstrated clinical usefulness in both hospital and community
      populations.

PMID- 15484280
TI  - Changes in the hemagglutinins and neuraminidases of human influenza B viruses
      isolated in Italy during the 2001-02, 2002-03, and 2003-04 seasons.
AB  - Throughout most of the last decade, B/Yamagata/16/88-lineage influenza viruses
      were predominant among the B isolates circulating worldwide, whereas
      B/Victoria/2/87-lineage viruses were isolated infrequently and restricted
      geographically to eastern Asia. During the 2001-02 influenza season,
      B/Victoria/2/87-lineage viruses re-emerged in North America and Europe and spread
      worldwide. Virological surveillance in Italy during that season showed wide
      circulation of influenza B viruses, of which most were antigenically related to
      the B/Sichuan/379/99 (Yamagata-lineage) vaccine strain, together with a smaller
      number of B viruses antigenically similar to B/HongKong/330/01, a recent
      B/Victoria/2/87-lineage antigenic variant. In the subsequent 2002-03 epidemic
      season, B viruses with a Victoria-lineage hemagglutinin (HA), more closely
      related to that of B/Shandong/7/97, were isolated exclusively. Similar strains
      have continued to predominate among the few B viruses isolated in Italy during
      last season (2003-04), although most influenza B viruses, isolated sporadically
      elsewhere in Europe, again belong to the Yamagata-lineage. In the present study,
      phylogenetic analyses of the HA and neuraminidase (NA) genes of representative B
      strains, isolated throughout Italy during 2001-04, showed that during the first
      influenza season the NA genes, as well as the HA genes, separated into the two
      distinct clades, the Yamagata- and Victoria-lineages, and showed no evidence of
      genetic reassortment. On the contrary, all the B viruses isolated in the 2002-03
      and most of those isolated in the 2003-04 epidemic season were "Victoria HA
      Yamagata NA" reassortants similar to those isolated in other parts of the world,
      showing that these reassortants became established in the human population. The
      frequency of reassortment between HA and NA of distinct lineages and sublineages
      highlights again the importance of detailed molecular analyses of both surface
      glycoproteins in understanding the evolution of influenza B viruses.

PMID- 15484281
TI  - Sequence variability of the alpha-chemokine UL146 from clinical strains of human
      cytomegalovirus.
AB  - Human cytomegalovirus (HCMV) is a ubiquitous pathogen that infects a variety of
      cell types in vivo. A region (referred to as UL/b') present in the Toledo strain
      of HCMV and low passage clinical isolates contains 22 additional genes, which are
      absent in the highly passaged laboratory strain AD169. One of these genes, UL146,
      encodes an alpha-chemokine. PCR amplification and sequencing of this gene from
      serial samples obtained from transplant recipients and samples from infants with
      suspected congenital HCMV infection, revealed that UL146 is a hypervariable gene
      in vivo. However, genetic changes were highly conserved in individuals and in
      renal transplant recipients multiple genotypes of UL146 were present. The
      majority of strains characterized maintained the conserved ELRCXC motif present
      in the Toledo strain of HCMV. These results provide further evidence that AD169
      does not represent the authentic virus in vivo and although Towne and Toledo are
      more representative, major genetic differences still exist. Mixed populations of
      HCMV strains occur in vivo so cloning of these strains is essential if an
      authentic genotype is to be defined.

PMID- 15484282
TI  - Sensitive and specific detection of strains of Japanese encephalitis virus using
      a one-step TaqMan RT-PCR technique.
AB  - A rapid, sensitive, and accurate laboratory diagnostic test is needed for
      distinguishing Japanese encephalitis virus (JEV) from other diseases featuring
      similar clinical symptoms and also for preventing potential outbreaks. In this
      study, a TaqMan reverse transcription (RT)-polymerase chain reaction (PCR) assay
      was developed for rapid detection and quantification of the viral RNA of various
      JEV strains. A consensus JEV NS3 region was chosen to design the primers and the
      TaqMan probe. The JEV TaqMan assay used the EZ-rTtH RT-PCR system featuring
      advantages such as a one-step, high-temperature RT reaction modality and
      preventing carry-over contamination. The sensitivity of the JEV TaqMan assay for
      detecting in vitro-transcribed JEV NS3 RNA was estimated to be one to five copies
      of RNA per reaction. For cultured JE virions, less than 40 plaque forming unit
      (PFU)/ml of virus load (corresponding to 0.07 PFU/test) could be detected. In
      addition, the JEV TaqMan assay could detect all seven strains of JEV tested, but
      provided negative results for nine other flaviviruses and encephalitis viruses
      tested. The JEV TaqMan assay demonstrated greater sensitivity and specificity
      than traditional RT-PCR methods as has been previously reported. The application
      of the JEV TaqMan assay herein has been shown to the sensitive detection of the
      JEV from both mosquito pools and also JEV-spiking human blood. The assay should
      be of use in diagnostic laboratory conduct and could be used to replace or
      complement time-consuming viral-culture methods, thus achieving more rapid,
      sensitive, and highly specific identification of JEV infection.

PMID- 15484283
TI  - Evaluation of a peptide-based enzyme immunoassay for anti-SARS coronavirus IgG
      antibody.
AB  - High throughput assays for anti-SARS-CoV IgG antibody detection are need for
      large-scale epidemiologic studies. The performance of a microplate enzyme
      immunoassay, DETECT-SARS was evaluated for the detection of anti-SARS-CoV IgG
      antibody. This assay is based on synthetic peptides derived from the nucleocapsid
      and spike proteins. The results showed that the assay provided a high degree of
      sensitivity (95.9%) for convalescent serum samples. The level of specificity was
      close to 90%, and did not show significant variation among different control
      groups. The high degree of sensitivity together with the high-throughput nature
      makes it advantageous as a screening assay for studies where handling of a large
      number of specimens is required.

PMID- 15484284
TI  - Complete sequence of a Kyrgyzstan swine hepatitis E virus (HEV) isolated from a
      piglet thought to be experimentally infected with human HEV.
AB  - Hepatitis E virus (HEV) was identified by RT-PCR amplification with degenerate
      ORF2 primers in the stool of a piglet experimentally inoculated with a stool
      suspension from a patient with acute hepatitis during an outbreak of non-A, non-B
      hepatitis in Kyrgyzstan. Further characterization by sequencing of the complete
      genome and phylogenetic analysis showed that the piglet isolate was most closely
      related to HEV genotype 3. Because the original human stool specimen used to
      inoculate the piglet was no longer available, stool samples from three patients
      obtained during the same outbreak were sequenced and found to be HEV genotype 1.
      These findings suggest that the HEV isolated from the swine stool was probably an
      HEV enzootic in Kyrgyzstan and not the virus inoculated from the human stool.

PMID- 15484285
TI  - Limitations of codon adaptation index and other coding DNA-based features for
      prediction of protein expression in Saccharomyces cerevisiae.
AB  - The relationship between codon usage and protein/mRNA expression in S. cerevisiae
      has been extensively studied. Recently, protein expression data for the whole
      yeast genome was published. We investigate which properties of coding DNA
      sequences can be used to predict expression levels. The new algorithm by Carbone
      et al. for computing dominating codon bias in a genome is evaluated. It is
      concluded that it works at least as well as existing methods, and eliminates the
      need to arbitrarily choose a set of highly expressed genes. Also, the hypothesis
      that information on codon pair frequencies can be used to predict expression is
      investigated. Our conclusion is that codon pairs do not contribute more
      information than do single codon frequencies. Overall correlation between
      predicted and actual expression data using properties of coding DNA sequences is
      around 0.65. Hence, while being a useful source of information, the expression
      levels predicted by these methods should only be used as a rule of thumb.

PMID- 15484286
TI  - Mycosporine-glutaminol-glucoside, a UV-absorbing compound of two Rhodotorula
      yeast species.
AB  - High-performance liquid chromatography (HPLC), alone or in combination with mass
      spectrometry (MS), was used to screen the basidiomycetous yeasts Rhodotorula
      minuta and R. slooffiae isolated from lakes for the presence of UV-absorbing
      compounds. Mycosporine-glutaminol-glucoside (maximum absorption, 310 nm), a UV
      photoprotective mycosporine known in terrestrial fungi, was the major UV
      absorbing compound found in these species. This is the first identification of a
      mycosporine in yeasts. The presence of this compound seems to be a promising
      chemotaxonomical marker for yeast systematics.

PMID- 15484287
TI  - An in vitro assay for (1 --> 6)-beta-D-glucan synthesis in Saccharomyces
      cerevisiae.
AB  - (1 --> 6)-beta-D-glucan is a key cell wall component of Saccharomyces cerevisiae
      and Candida albicans. Many genes are known to affect the levels or structure of
      this glucan, but their roles and a molecular description of the synthesis of (1 -
      > 6)-beta-D-glucan remain to be established and a method to measure (1 --> 6)
      beta-D-glucan synthase activity in vitro would provide an enabling tool. Here,
      conditions for the detection of in vitro synthesis of this polymer are described.
      Crude membrane preparations from S. cerevisiae were isolated, and incubated in
      the presence of UDP-glucose and GTP. With anti-(1 --> 6)-beta-D-glucan-specific
      antibodies, a time-dependent increase in the amount of this glucan was
      demonstrated in a dot-blot assay, or through an inhibition enzyme immunoassay.
      Antibody specificity was validated by competition experiments using pustulan, a
      (1 --> 6)-beta-D-glucan, laminarin, a (1 --> 3)-beta-D-glucan, yeast mannan and
      glycogen. The identity of the reaction product was also demonstrated by its
      sensitivity to a recombinant (1 --> 6)-beta-D-glucanase. Extracts from mutants in
      10 genes with a wide range of altered cell wall (1 --> 6)-beta-D-glucan levels
      were assayed for in vitro synthesis of the polymer. A strong correlation of in
      vitro synthase activity with in vivo glucan levels was found, providing genetic
      support for the specificity of the assay. The basis for the GTP-dependence of the
      synthase reaction was studied. Extracts from rho2, rho3, rho4 and rho5 null
      mutants had wild-type in vitro activity. In contrast, Rho1p overproduction led to
      increased in vitro synthesis, implicating Rho1p in the regulation of (1 --> 6)
      beta-D-glucan synthesis.

PMID- 15484288
TI  - The cell wall sensor Wsc1p is involved in reorganization of actin cytoskeleton in
      response to hypo-osmotic shock in Saccharomyces cerevisiae.
AB  - The cell wall is essential to preserve osmotic integrity of yeast cells. Some
      phenotypic traits of cell wall mutants suggest that, as a result of a weakening
      of the cell wall, hypo-osmotic stress-like conditions are created. Consequent
      expansion of the cell wall and stretching of the plasma membrane trigger a
      complex response to prevent cell lysis. In this work we examined two conditions
      that generate a cell wall and membrane stress: one is represented by the cell
      wall mutant gas1Delta and the other by a hypo-osmotic shock. We examined the
      actin cytoskeleton and the role of the cell wall sensors Wsc1p and Mid2p in these
      stress conditions. In the gas1 null mutant cells, which lack a beta(1,3)
      glucanosyltransferase activity required for cell wall assembly, a constitutive
      marked depolarization of actin cytoskeleton was found. In a hypo-osmotic shock
      wild-type cells showed a transient depolarization of actin cytoskeleton. The
      percentage of depolarized cells was maximal at 30 min after the shift and then
      progressively decreased until cells reached a new steady-state condition. The
      maximal response was proportional to the magnitude of the difference in the
      external osmolarity before and after the shift within a given range of
      osmolarities. Loss of Wsc1p specifically delayed the repolarization of the actin
      cytoskeleton, whereas Wsc1p and Mid2p were essential for the maintenance of cell
      integrity in gas1Delta cells. The control of actin cytoskeleton is an important
      element in the context of the compensatory response to cell wall weakening. Wsc1p
      appears to be an important regulator of the actin network rearrangements in
      conditions of cell wall expansion and membrane stretching.

PMID- 15484289
TI  - Characterization of a gene similar to BIK1 in the yeast Kluyveromyces lactis.
AB  - In Saccharomyces cerevisiae, Bik1p is a microtubule plus-end-tracking protein
      that plays several roles in mitosis and ploidy. KlBik1p (from Kluyveromyces
      lactis) maintains the same structural-domain organization as does S. cerevisiae
      Bik1p. As part of its characterization, we constructed a stable klbik1 mutant
      which is sensitive to benomyl only at 14 degrees C and has a higher frequency of
      crescent-shaped nuclei than S. cerevisiae bik1 mutants. This phenotype is
      partially rescued by S. cerevisiae BIK1. Other phenotypes associated with bik1
      are not present in the K. lactis mutant. By fusion to GFP we were able to show
      the functionality of the KlBik1p CAP-Gly domain and found that the fusion protein
      changes its cellular location during the cell cycle.

PMID- 15484290
TI  - Mating-induced mating-type cassette conversion in Saccharomyces cerevisiae.
AB  - We have previously reported that the HMRa-bearing restriction fragment of a rho
      degrees sir4-11 strain (HMLalpha-MATalpha-HMRa), which acts as an alpha-mater
      because of being rho degrees , changes its electrophoretic mobility when the
      strain mates with a certain group of a-mating strains (HMLalpha-MATa-HMRa). In
      this study, we found that the sir4-11 strain being rho degrees was not essential
      for this phenomenon and also that the altered form of the fragment contained
      HMRalpha in place of HMRa. Furthermore, we observed conversion of HMLa to
      HMLalpha in the cross in which a sir4-11 HMLa-MATalpha-HMRalpha strain was mated
      with a representative of the above-mentioned a-mating strain. In addition, when
      this a-mating strain was mated with a SIR(+) HMLalpha-MATa-HMRalpha strain, the
      resultant diploid was found to be HMLalpha/HMLalpha MATa/MATalphaHMRa/HMRalpha,
      indicating that conversion of MATa to MATalpha had taken place in the course of
      mating. From all these observations, we conclude that there is a group of S.
      cerevisiae strains that carries factor(s) that induces conversion of a mating
      type cassette of the mating partner to alpha mating-type cassette and that this
      mating type cassette conversion takes place in all three mating type loci, HML,
      MAT and HMR, if the loci are in the non-silenced condition.

PMID- 15484291
TI  - Prognostic and clinicopathological features of E-cadherin, alpha-catenin, beta
      catenin, gamma-catenin and cyclin D1 expression in human esophageal squamous cell
      carcinoma.
AB  - AIM: To investigate the expression of E-cadherin, alpha-catenin, beta-catenin,
      gamma-catenin and cyclin D(1) in patients with esophageal squamous cell carcinoma
      (ESCC), and analyze their interrelationship with clinicopathological variables
      and their effects on prognosis. METHODS: Expression of E-cadherin, alpha-catenin,
      beta-catenin, gamma-catenin and cyclin D(1) was determined by EnVision or SABC
      immunohistochemical technique in patients with ESCC consecutively, their
      correlation with clinical characteristics was evaluated and analyzed by
      univariate analysis. RESULTS: The reduced expression rate of E-cadherin, alpha
      catenin, beta-catenin and gamma-catenin was 88.7%, 69.4%, 35.5% and 53.2%,
      respectively. Cyclin D1 positive expression rate was 56.5%. Expression of gamma
      catenin was inversely correlated with the degree of tumor differentiation and
      lymph node metastasis (chi(2) = 4.183 and chi(2) = 5.035, respectively, P<0.05),
      whereas the expression of E-cadherin was correlated only with the degree of
      differentiation (chi(2) = 5.769, P<0.05). Reduced expression of E-cadherin and
      gamma-catenin was associated with poor differentiation of tumor, reduced
      expression of gamma-catenin was also associated with lymph node metastasis. There
      obviously existed an inverse correlation between level of E-cadherin and gamma
      catenin protein and survival. The 3-year survival rates were 100% and 56% in E
      cadherin preserved expression group and in reduced expression one and were 78%
      and 48% in gamma-catenin preserved expression group and in reduced expression
      one, respectively. The differences were both statistically significant.
      Correlation analysis showed the expression level of alpha-catenin correlated with
      that of E-cadherin and beta-catenin (P<0.05). CONCLUSION: The reduced expression
      of E-cadherin and gamma-catenin, but not alpha-catenin, beta-catenin and cyclin
      D1, implies more aggressive malignant behaviors of esophageal carcinoma cells and
      predicts the poor prognosis of patients.

PMID- 15484292
TI  - Elevated level of spindle checkprotein MAD2 correlates with cellular mitotic
      arrest, but not with aneuploidy and clinicopathological characteristics in
      gastric cancer.
AB  - AIM: To study the relevance of spindle assembly checkprotein MAD2 to cellular
      mitotic status, aneuploidy and other clinicopathological characteristics in
      gastric cancer. METHODS: Western blot analyses were performed to analyze the
      protein levels of MAD2 and cyclin B1 in the tumorous and adjacent nontumorous
      tissues of 34 gastric cancer patients. Cell cycle distribution and DNA ploidy of
      cancer tissues were also determined by flow cytometry. Conventional statistical
      methods were adopted to determine the relevance of abnormal MAD2 level to mitotic
      status, aneuploidy and clinicopathological parameters. RESULTS: Out of 34 gastric
      cancer patients 25 (74%) exhibited elevated MAD2 levels in their tumorous tissues
      compared with the corresponding nontumorous tissues. Elevation of MAD2 levels
      significantly correlated with the increased levels of cyclin B1 expression and
      G(2)/M-phase distribution (P = 0.038 and P = 0.033, respectively), but was not
      relevant to aneuploidy. The gastric cancer patients with elevated MAD2 levels
      showed a tendency toward better disease-free and overall survival (P>0.05).
      However, no association was found between elevated MAD2 levels and patients'
      clinicopathological characteristics. CONCLUSION: Elevation of MAD2 level is
      present in 74% of gastric cancer patients, and correlates with increased mitotic
      checkpoint activity. However, elevation of MAD2 level is not associated with
      patients' aneuploidy and any of the clinicopathological characteristics.

PMID- 15484293
TI  - Expression level of wild-type survivin in gastric cancer is an independent
      predictor of survival.
AB  - AIM: Survivin is a novel antiapoptotic gene in which three splicing variants have
      been recently cloned and characterized. Survivin has been found to be abundantly
      expressed in a wide variety of human malignancies, whereas it is undetectable in
      normal adult tissues. We aimed to study the expression of three survivin splicing
      variants in gastric cancer, and to evaluate the prognostic significance of the
      expression of survivin variants in gastric cancer. METHODS: Real time
      quantitative RT-PCR was performed to analyze the expression of survivin variants
      in 79 paired tumors and normal gastric mucosa samples at the mRNA level.
      Proliferative and apoptotic activity was measured using Ki-67 immunohistochemical
      analysis and the TUNEL method, respectively. RESULTS: All the cases tested
      expressed wild-type survivin mRNA, which was not only the dominant transcript,
      but also a poor prognostic biomarker (P = 0.003). Non-antiapoptostic survivin-2B
      mRNA was correlated with tumor stage (P = 0.001), histological type (P = 0.004),
      and depth of tumor invasion (P = 0.041), while survivin-DeltaEx3 mRNA showed a
      significant association with apoptosis (P = 0.02). CONCLUSION: Wild-type survivin
      mRNA expression levels are of important prognostic value and significant
      participation of survivin-2B and survivin-DeltaEx3 is suggested in gastric cancer
      development.

PMID- 15484294
TI  - Detection of bcl-2 and bax expression and bcl-2/JH fusion gene in intrahepatic
      cholangiocarcinoma.
AB  - AIM: To investigate the relationship between bcl-2 gene and its related protein
      bax and intrahepatic cholangiocellular carcinoma (CCC). METHODS: Semi-nested in
      situ PCR (SNISPCR) and immunohistochemistry were performed to detect bcl-2/JH
      fusion gene and bcl-2, bax protein expression in 29 cases of CCC. RESULTS: No bcl
      2/JH fusion gene was found in all cases of CCC, 72.4% of 29 cases expressed bcl-2
      protein. Bcl-2 protein expression was related to histopathological grades
      (P<0.05). There was no corresponding relationship between bcl-2/JH fusion gene
      formation and bcl-2 protein expression in CCC (P<0.05). Bax was expressed in
      10.3% of 29 cases. The ratio of bcl-2 to bax in normal liver tissues (3.5 to 1)
      was different from that in tumor tissues (7.0 to 1). CONCLUSION: It is suggested
      that bcl-2/JH fusion gene formation is not a frequent event and may not play an
      important role in the pathogenesis of CCC. However, aberrant ratio of bcl-2 to
      bax protein expression may be involved in the course of tumorigenesis of CCC.
      Abnormal bcl-2 protein expression may not be solely resulted from bcl-2/JH fusion
      gene.

PMID- 15484295
TI  - Nuclear factor-kappaB p65 (RelA) transcription factor is constitutively activated
      in human colorectal carcinoma tissue.
AB  - AIM: Activation of transcription factor nuclear factor-kappaB (NF-kappaB) has
      been shown to play a role in cell proliferation, apoptosis, cytokine production,
      and oncogenesis. The purpose of this study was to determine whether NF-kappaB was
      constitutively activated in human colorectal tumor tissues and, if so, to
      determine the role of NF-kappaB in colorectal tumorigenesis, and furthermore, to
      determine the association of RelA expression with tumor cell apoptosis and the
      expression of Bcl-2 and Bcl-x(L). METHODS: Paraffin sections of normal
      epithelial, adenomatous and adenocarcinoma tissues were analysed
      immunohistochemically for expression of RelA, Bcl-2 and Bcl-x(L) proteins.
      Electrophoretic mobility shift assay (EMSA) was used to confirm the increased
      nuclear translocation of RelA in colorectal tumor tissues. The mRNA expressions
      of Bcl-2 and Bcl-x(L) were determined by reverse transcription polymerase chain
      reaction (RT-PCR) analysis. Apoptotic cells were detected by terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick
      end labeling (TUNEL) method. RESULTS: The activity of NF-kappaB was significantly
      higher in adenocarcinoma tissue in comparison with that in adenomatous and normal
      epithelial tissues. The apoptotic index (AI) significantly decreased in the
      transition from adenoma to adenocarcinoma. Meanwhile, the expressions of Bcl-2
      and Bcl-x(L) protein and their mRNAs were significantly higher in adenocarcinoma
      tissues than that in adenomatous and normal epithelial tissues. CONCLUSION: NF
      kappaB may inhibit apoptosis via enhancing the expression of the apoptosis genes
      Bcl-2 and Bcl-x(L). And the increased expression of RelA/nuclear factor-kappaB
      plays an important role in the pathogenesis of colorectal carcinoma.

PMID- 15484296
TI  - Expression of vascular endothelial growth factor-C and the relationship between
      lymphangiogenesis and lymphatic metastasis in colorectal cancer.
AB  - AIM: To investigate the expression of vascular endothelial growth factor-C (VEGF
      C) and the relationship between VEGF-C and lymphangiogenesis, lymph node
      metastasis in colorectal cancer. METHODS: Fifty six cases of colorectal cancer
      were selected randomly. Expression of VEGF-C was detected by
      immunohistochemistry, and lymphatic vessels were stained by enzyme histochemical
      method. RESULTS: VEGF-C expression was found in 66.7% (37/56) patients. In VEGF-C
      positive and negative patients, the lymphatic vessel density was 25.16+/-7.52 and
      17.14+/-7.22, respectively (P<0.05). The rate of lymph node metastasis in VEGF-C
      positive patients (81.1%) was significantly higher than that in the negative
      group (42.1%). CONCLUSION: VEGF-C expression may induce lymphangiogenesis in
      colorectal cancer, as a result, tumor cells can entry the lymphatic vessels
      easily. VEGF-C may serve as a useful prognotic factor in colorectal carcinoma.

PMID- 15484297
TI  - Hepatitis B virus genotypes, phylogeny and occult infection in a region with a
      high incidence of hepatocellular carcinoma in China.
AB  - AIM: To determine the genotypes and phylogeny of hepatitis B viruses (HBVs) in
      asymptomatic HBV carriers, and the prevalence of occult HBV infection in Long An
      County, Guangxi Zhuang Autonomous Region, an area with a high incidence of
      hepatocellular carcinoma. METHODS: A nested polymerase chain reaction (nPCR) was
      used for detection of HBV DNA in serum samples from 36 blood donors with
      asympmatic HBV infection, and in serum samples from 52 HBsAg negative family
      members of the children who did not receive hepatitis B vaccination in Long An
      County. PCR products were sequenced, and the genotype of each HBV sequence was
      determined by comparison with sequences of known genotypes in the GenBank and
      EMBL nucleotide databases using the BLAST programme. Phylogenetic trees were
      constructed by the quartet maximum likelihood analysis using the TreePuzzle
      software. RESULTS: Twenty (55.56%) of 36 HBV asymptomatic carriers were positive
      for HBV DNA. They were all genotype C by comparison with sequences of known
      genotypes in the GenBank and EMBL nucleotide databases. The full-length HBV DNA
      sequence isolated from the sample No. 624 contained 3 215 bases. No interesting
      mutations were found in this isolate. The homology analysis showed that this
      strain was closer to the Vietnamese HBV genotype C strain, with a homology of
      97%, compared its relation to the same genotype of HBV isolated in Shanghai. Six
      (11.5%) of the 52 HBsAg negative family members were positive for HBV DNA. A
      point mutation was found in the sample No. 37, resulting in the substitution of
      amino acid glycine to arginine in the "a" determinant. Other samples with
      positive HBV DNA did not have any unusual amino acid substitutions in or around
      the "a" determinant, and were attributed to the wild-type HBV. CONCLUSION: The
      HBVs isolated from asymptomatic carriers of Long An County were all identified as
      genotype C, and the prevalence of occult HBV infection in the population of the
      county is as high as 11.5%. It is suggested that genotype C and persistent occult
      HBV infection may play an important role in the development of HCC in the county.

PMID- 15484298
TI  - Capsule oxymatrine in treatment of hepatic fibrosis due to chronic viral
      hepatitis: a randomized, double blind, placebo-controlled, multicenter clinical
      study.
AB  - AIM: To evaluate the efficacy and safety of oxymatrine capsule in treatment of
      hepatic fibrosis in patients with chronic viral hepatitis. METHODS: It was a
      randomized, double blind, placebo-controlled, multicenter clinical study. One
      hundred and forty-four patients were divided into oxymatrine capsule group(group
      A) and placebo group (group B). The course was 52 wk. Patients were visited once
      every 12 wk and the last visit was at 12 wk after cessation of the treatment. All
      patients had liver biopsy before treatment. part of them had a second biopsy at
      the end of therapy. Clinical symptoms, liver function test, serum markers of
      hepatic fibrosis were tested. Ultrasound evaluation was performed before, during
      and at the end of therapy. RESULTS: One hundred and forty-four patients enrolled
      in the study. Of them 132 patients completed the study according to the
      protocol,49 patients had liver biopsy twice (25 patients in group A and 24 in
      group B). At the end of therapy, significant improvements in hepatic fibrosis and
      inflammatory activity based on Semi-quantitative scoring system (SSS) were
      achieved in group A. The total effective rate of the treatment was 48.00%, much
      higher than that of 4.17% in group B (P<0.05). Significant improvement in serum
      markers of hepatic fibrosis such as hyaluronic acid (HA) and type III
      procollagenic peptide (P III P) in group A was seen (P<0.05). The total effective
      rate of serum markers at the end of therapy in group A was 68.19%, much higher
      than that of 34.85% in group B (P<0.05). The total effective rate of noninvasive
      markers at the end of therapy in group A was 66.67%, much higher than that of
      30.30% in group B (P<0.05). The rate of adverse events was similar in two groups.
      CONCLUSION: Oxymatrine capsule is effective and safe in treatment of hepatic
      fibrosis due to chronic viral hepatitis.

PMID- 15484299
TI  - Neither gastric topological distribution nor principle virulence genes of
      Helicobacter pylori contributes to clinical outcomes.
AB  - AIM: Studies on Helicobacter pylori (H pylori) and gastroduodenal diseases have
      focused mainly on the distal sites of the stomach, but relationship with the
      gastric cardia is lacking. The aim of this study is to determine if the gastric
      topology and genotypic distribution of H pylori were associated with different
      upper gastrointestinal pathologies in a multiethnic Asian population. METHODS:
      Gastric biopsies from the cardia, body/corpus and antrum were endoscoped from a
      total of 155 patients with dyspepsia and/or reflux symptoms, with informed
      consent. H pylori isolates obtained were tested for the presence of 26 kDa, ureC,
      cagA, vacA, iceA1, iceA2 and babA2 genes using PCR while DNA fingerprints were
      generated using random amplification polymorphic DNA (RAPD). RESULTS: H pylori
      was present in 51/155 (33%) of patients studied. Of these, 16, 15 and 20 were
      isolated from patients with peptic ulcer diseases, gastroesophageal reflux
      diseases and non-ulcer dyspepsia, respectively. Of the H pylori positive
      patients, 75% (38/51) had H pylori in all three gastric sites. The prevalence of
      various genes in the H pylori isolates was shown to be similar irrespective of
      their colonization sites as well as among the same site of different patients.
      The RAPD profiles of H pylori isolates from different gastric sites were highly
      similar among intra-patients but varied greatly between different patients.
      CONCLUSION: Topographic colonization of H pylori and the virulence genes
      harboured by these isolates have no direct bearing to the clinical state of the
      patients. In multi-ethnic Singapore, the stomach of each patient is colonized by
      a predominant strain of H pylori, irrespective of the clinical diagnosis.

PMID- 15484300
TI  - A novel genetic polymorphism of inducible nitric oxide synthase is associated
      with an increased risk of gastric cancer.
AB  - AIM: Inducible nitric oxide synthase (iNOS) plays a central role in the pathway
      of reactive oxygen and nitrogen species metabolism when Helicobacter pylori (H
      pylori) infection occurs in humans. iNOS Ser(608)Leu allele, a novel genetic
      polymorphism (C/T) occurring within exon 16 of the iNOS reductase domain, may
      have a dramatic effect on the enzymatic activity. The aim of this study was to
      determine whether iNOS C/T polymorphism was associated with increased
      susceptibility to gastric cancer. METHODS: We conducted a population based case
      control study in a high gastric cancer incidence area, Yangzhong, China.
      Questionnaires from 93 patients with intestinal type gastric cancer (IGC), 50
      with gastric cardia cancer (GCC) and 246 healthy controls were obtained between
      1997 and 1998, and iNOS genotyping was carried out. Odds ratios (ORs),
      interaction index (gamma), and 95% confidence intervals for the combined effects
      of iNOS genotype and H pylori infection, cigarette smoking or alcohol drinking
      were estimated. RESULTS: The frequency of (CT+TT) genotypes was higher in cases
      than in control group (24.48% vs 23.17%), but the difference was not
      statistically significant. After adjusting for age and gender, past cigarette
      smokers with (CT+TT) genotypes had a significantly increased risk of IGC (OR =
      3.62, 95% CI: 1.23-10.64), while past alcohol drinkers with (CT+TT) genotypes had
      a significantly increased risk of GCC (OR = 3.33, 95% CI: 1.14-9.67). H pylori
      CagA negative subjects with (CT+TT) genotypes had a significantly increased risk
      of both IGC and GCC (OR = 2.19 and 3.52, respectively). CONCLUSION: iNOS
      Ser(608)Leu allele may be a potential determinant of susceptibility to cigarette 
      alcohol induced gastric cancer, but larger studies are needed to confirm the
      observations.

PMID- 15484301
TI  - A new subtype of 3' region of cagA gene in Helicobacter pylori strains isolated
      from Zhejiang Province in China.
AB  - AIM: To isolate the subtypes of 3' region of cagA gene in Helicobacter pylori (H
      pylori) strains from Zhejiang Province in China and to investigate their
      relations to H pylori-associated gastroduodenal diseases. METHODS: One hundred
      and thirty-seven H pylori clinical strains were isolated from the gastric mucosa
      specimens of 74 patients with chronic gastritis, 61 with peptic ulceration, and 2
      with gastric cancer. Bacterial genomic DNA was extracted and 3' region of cagA
      gene was amplified by polymerase chain reaction (PCR). Subtypes of 3' region of
      cagA gene were determined by the size of PCR amplified segments. The sequences of
      the subtypes were analyzed by PCR-based sequencing. RESULTS: Of the 137 H pylori
      isolates from Zhejiang Province, 132 (96.4%) yielded PCR products that could be
      classified into three groups of subtypes, named as subtypes I, II, and III
      according to their sizes. The sizes of subtypes I, II, and III were 648-650 bp,
      705-707 bp, and 815 bp, respectively. Among the 132 cagA-positive H pylori
      strains, 123 (93.2%) belonged to the group of subtype I, 6 (4.5%) presented
      subtype II, 1 (0.8%) was subtype III, and 2 (1.5%) presented subtypes I and III
      both. The primary structure of subtype I was composed of 3 repeats of R1, 1
      repeat of R2 and 1 repeat of R3. Subtype II possessing 4 repeats of R1, 2 repeats
      of R2 and 1 repeat of R3 was a newly found type of 3' region of cagA gene which
      had not been reported before. The primary structure of subtype III consisted of 4
      repeats of R1, 1 repeat of R2 and 2 repeats of R3. Comparison of the sequences of
      subtype I strains with the corresponding sequences deposited in GenBank, showed a
      similarity of 95.0% (94.0-96.1%) for nucleotide sequences and 95.9% (94.9-97.4%)
      for deduced amino acid sequences. Comparison of the sequences of subtype III
      strains with the corresponding sequences deposited in GenBank, showed a
      similarity of 93.9% (90.8-96.9%) for nucleotide sequences and 93.2% (90.2-96.2%)
      for deduced amino acid sequences. Among subtype II strains, the nucleotide and
      deduced amino acid sequences showed a similarity of 95.2% (94.1-96.5%) and 96.4%
      (93.8-97.9%), respectively. There were no statistical differences in the
      distribution of subtypes of 3' region of cagA gene among different H pylori
      associated gastroduodenal diseases (chi(2) = 11.544, P>0.05). CONCLUSION: There
      are three subtypes (I, II, and III) of 3' region of cagA gene in H pylori strains
      isolated from Zhejiang Province, and subtypeIis predominant. Subtype II is a
      newly found subtype of 3' region of cagA gene. The result of this study does not
      support the view that the subtypes of 3' region of cagA gene in H pylori isolated
      from Zhejiang Province are correlated with the clinical outcomes of H pylori
      infection.

PMID- 15484302
TI  - Pathogenicty and immune prophylaxis of cag pathogenicity island gene knockout
      homogenic mutants.
AB  - AIM: To clarify the role of cag pathogenicity island (cagPAI) of Helicobacter
      pylori (H pylori ) in the pathogenicity and immune prophylaxis of H pylori
      infection. METHODS: Three pairs of H pylori including 3 strains of cagPAI
      positive wildtype bacteria and their cagPAI knockout homogenic mutants were
      utilized. H pylori binding to the gastric epithelial cells was analyzed by flow
      cytometry assays. Apoptosis of gastric epithelial cells induced by H pylori was
      determined by ELISA assay. Prophylaxis effect of the wildtype and mutant strains
      was compared by immunization with the sonicate of the bacteria into mice model.
      RESULTS: No difference was found in the apoptasis between cagPAI positive and
      knockout H pylori strains in respective of the ability in the binding to gastric
      epithelial cells as well as the induction of apoptosis. Both types of the
      bacteria were able to protect the mice from the infection of H pylori after
      immunization, with no difference between them regarding to the protection rate as
      well as the stimulation of the proliferation of splenocytes of the mice.
      CONCLUSION: The role of cagPAI in the pathogenicity and prophylaxis of H pylori
      infection remains to be cleared.

PMID- 15484304
TI  - Coxsackievirus B3 infection and its mutation in Keshan disease.
AB  - AIM: To investigate coxsackievirus B(3) infection and its gene mutation in Keshan
      disease. METHODS: The expression of Coxsackievirus B(3) RNA was detected in
      autopsy specimens of acute (12 cases), sub-acute (27 cases) and chronic (15
      cases) Keshan disease by in situ hybridization. In sub-acute Keshan disease
      specimens, 3 cases with positive result by in situ hybridization were selected RT
      PCR analysis. The DNA segments were then sequenced. RESULTS: Coxsackievirus B(3)
      RNA was detected in the cytoplasm of myocardiocyte. The positive rate was 83% in
      acute, 67% in sub-acute and 80% in chronic Keshan disease. In the conservative
      region of Coxsackievirus B(3) genome, there was a mutation in 234 (C-T) compared
      to the non-cardiovirulent strain, CVB(3/0). CONCLUSION: Coxsackievirus B(3) RNA
      can survive and replicate in heart muscle of Keshan disease, which may play an
      important role in the occurrence of Keshan disease. The possible mechanism of
      occurrence of Keshan disease is associated with point a mutation in
      Coxsackievirus B(3) genome.

PMID- 15484303
TI  - Mechanisms mediating cholinergic antral circular smooth muscle contraction in
      rats.
AB  - AIM: To investigate the pathway (s) mediating rat antral circular smooth muscle
      contractile responses to the cholinomimetic agent, bethanechol and the subtypes
      of muscarinic receptors mediating the cholinergic contraction. METHODS: Circular
      smooth muscle strips from the antrum of Sprague-Dawley rats were mounted in
      muscle baths in Krebs buffer. Isometric tension was recorded. Cumulative
      concentration-response curves were obtained for (+)-cis-dioxolane (cD), a
      nonspecific muscarinic agonist, at 10(-8)-10(-4) mol/L, in the presence of
      tetrodotoxin (TTX, 10(-7) mol/L). Results were normalized to cross sectional
      area. A repeat concentration-response curve was obtained after incubation of the
      muscle for 90 min with antagonists for M1 (pirenzepine), M2 (methoctramine) and
      M3 (darifenacin) muscarinic receptor subtypes. The sensitivity to PTX was tested
      by the ip injection of 100 mg/kg of PTX 5 d before the experiment. The antral
      circular smooth muscles were removed from PTX-treated and non-treated rats as
      strips and dispersed smooth muscle cells to identify whether PTX-linked pathway
      mediated the contractility to bethanechol. RESULTS: A dose-dependent contractile
      response observed with bethanechol, was not affected by TTX. The pretreatment of
      rats with pertussis toxin decreased the contraction induced by bethanechol. Lack
      of calcium as well as the presence of the L-type calcium channel blocker,
      nifedipine, also inhibited the cholinergic contraction, with a reduction in
      response from 2.5+/-0.4 g/mm2 to 1.2+/-0.4 g/mm(2) (P<0.05). The dose-response
      curves were shifted to the right by muscarinic antagonists in the following order
      of affinity: darifenacin (M(3))>methocramine (M(2)) >pirenzepine (M(1)).
      CONCLUSION: The muscarinic receptors-dependent contraction of rat antral circular
      smooth muscles was linked to the signal transduction pathway(s) involving
      pertussis-toxin sensitive GTP-binding proteins and to extracellular calcium via L
      type voltage gated calcium channels. The presence of the residual contractile
      response after the treatment with nifedipine, suggests that an additional pathway
      could mediate the cholinergic contraction. The involvement of more than one
      muscarinic receptor (functionally predominant type 3 over type 2) also suggests
      more than one pathway mediating the cholinergic contraction in rat antrum.

PMID- 15484305
TI  - Effect of actin microfilament on potassium current in guinea pig gastric
      myocytes.
AB  - AIM: To investigate the effect of actin microfilament on potassium current and
      hyposmotic membrane stretch-induced increase of potassium current in gastric
      antral circular myocytes of guinea pig. METHODS: Whole-cell patch clamp technique
      was used to record potassium current in isolated gastric myocyes. RESULTS: When
      the membrane potential was clamped at -60 mV, an actin microfilament disruptor,
      cytochanlasin-B(Cyt-B, 20 micromol/L in pipette) increased calcium-activated
      potassium current (I(K(Ca))) and delayed rectifier potassium current (I(K(V))) to
      138.4+/-14.3% and 142.1+/-13.1% respectively at +60 mV. In the same condition, an
      actin microfilament stabilizer phalloidin (20 micromol/L in pipette) inhibited
      I(K(Ca)) and I(K(V)) to 74.2+/-7.1% and 75.4+/-9.9% respectively. At the holding
      potential of -60 mV, hyposmotic membrane stretch increased I(K(Ca)) and I(K(V))
      by 50.6+/-9.7% and 24.9+/-3.3% at +60 mV respectively. In the presence of
      cytochalasin-B and phalloidin (20 micromol/L, in the pipette) condition,
      hyposmotic membrane stretch also increased I(K(Ca)) by 44.5+/-7.9% and 55.7+/
      9.8% at +60 mV respectively. In the same condition, cytochalasin-B and phalloidin
      also increased I(K(V)) by 23.0+/-5.5% and 30.3+/-4.5% respectively. However, Cyt
      B and phalloidin did not affect the amplitude of hyposmotic membrane stretch
      induced increase of I(K(Ca)) and I(K(V)). CONCLUSION: Actin microfilaments
      regulate the activities of potassium channels, but they are not involved in the
      process of hyposmotic membrane stretch-induced increase of potassium currents in
      gastric antral circular myocytes of guinea pig.

PMID- 15484306
TI  - Selection, proliferation and differentiation of bone marrow-derived liver stem
      cells with a culture system containing cholestatic serum in vitro.
AB  - AIM: To explore the feasibility of direct separation, selective proliferation and
      differentiation of the bone marrow-derived liver stem cells (BDLSC) from bone
      marrow cells with a culture system containing cholestatic serum in vitro.
      METHODS: Whole bone marrow cells of rats cultured in routine medium were replaced
      with conditioning selection media containing 20 mL/L, 50 mL/L, 70 mL/L, and 100
      mL/L cholestatic sera, respectively, after they attached to the plates. The
      optimal concentration of cholestatic serum was determined according to the
      outcome of the selected cultures. Then the selected BDLSC were induced to
      proliferate and differentiate with the addition of hepatocyte growth factor
      (HGF). The morphology and phenotypic markers of BDLSC were characterized using
      immunohistochemistry, RT-PCR and electron microscopy. The metabolic functions of
      differentiated cells were also determined by glycogen staining and urea assay.
      RESULTS: Bone marrow cells formed fibroblast-like but not hepatocyte-like
      colonies in the presence of 20 mL/L cholestatic serum. In 70 mL/L cholestatic
      serum, BDLSC colonies could be selected but could not maintain good growth
      status. In 100 mL/L cholestatic serum, all of the bone marrow cells were unable
      to survive. A 50 mL/L cholestatic serum was the optimal concentration for the
      selection of BDLSC at which BDLSC could survive while the other populations of
      the bone marrow cells could not. The selected BDLSC proliferated and
      differentiated after HGF was added. Hepatocyte-like colony-forming units (H-CFU)
      then were formed. H-CFU expressed markers of embryonic hepatocytes (AFP, albumin
      and cytokeratin 8/18), biliary cells (cytokeratin 19), hepatocyte functional
      proteins (transthyretin and cytochrome P450-2b1), and hepatocyte nuclear factors
      (HNF-1alpha and HNF-3beta). They also had glycogen storage and urea synthesis
      functions, two of the critical features of hepatocytes. CONCLUSION: The selected
      medium containing cholestatic serum can select BDLSC from whole bone marrow
      cells. It will be a new way to provide a readily available alternate source of
      cells for clinical hepatocyte therapy.

PMID- 15484307
TI  - Upper gastrointestinal endoscopy: are preparatory interventions or conscious
      sedation effective? A randomized trial.
AB  - AIM: The fears and concerns are associated with gastroscopy (EGD) decrease
      patient compliance. Conscious sedation (CS) and non-pharmacological interventions
      have been proposed to reduce anxiety and allow better execution of EGD. The aim
      of this study was to assess whether CS, supplementary information with a
      videotape, or presence of a relative during the examination could improve the
      tolerance to EGD. METHODS: Two hundred and twenty-six outpatients (pts),
      scheduled for a first-time non-emergency EGD were randomly assigned to 4 groups:
      Co-group (62 pts): throat anaesthesia only; Mi-group (52 pts): CS with i.v.
      midazolam; Re-group (58 pts): presence of a relative throughout the procedure; Vi
      group (54 pts): additional information with a videotape. Anxiety was measured
      using the "Spielberger State and Trait Anxiety Scales". The patients assessed the
      overall discomfort during the procedure on an 100-mm visual analogue scale, and
      their tolerance to EGD answering a questionnaire. The endoscopist evaluated the
      technical difficulty of the examination and the tolerance of the patients on an
      100-mm visual analogue scale and answering a questionnaire. RESULTS: Pre
      endoscopy anxiety levels were higher in the Mi-group than in the other groups
      (P<0.001). On the basis of the patients' evaluation, EGD was well tolerated by
      80.7% of patients in Mi-group, 43.5% in Co-group, 58.6% in Re-group, and 50% in
      Vi-group (P<0.01). The discomfort caused by EGD, evaluated by either the
      endoscopist or the patients, was lower in Mi-group than in the other groups. The
      discomfort was correlated with "age" (P<0.001) and "groups of patients" (P<0.05)
      in the patients' evaluation, and with "gender" (females tolerated better than
      males, P<0.001) and "groups of patients" (P<0.05) in the endoscopist's
      evaluation. CONCLUSION: Conscious sedation can improve the tolerance to EGD. Male
      gender and young age are predictive factors of bad tolerance to the procedure.

PMID- 15484308
TI  - Opisthorchiasis-associated biliary stones: light and scanning electron
      microscopic study.
AB  - AIM: Biliary stones are frequently encountered in areas endemic for
      opisthorchiasis in Thailand. The present study was to describe the prevalence and
      pathogenesis of these stones. METHODS: Gallstones and/or common bile duct stones
      and bile specimens from 113 consecutive cholecystectomies were included. Bile
      samples, including sludge and/or microcalculi, were examined for Opisthorchis
      viverrini eggs, calcium and bilirubin. The stones were also processed for
      scanning electron microscopic (SEM) study. RESULTS: Of the 113 cases, 82 had
      pigment stones, while one had cholesterol stones. The other 30 cases had no
      stones. Most of the stone cases (76%, 63/83) had multiple stones, while the
      remainder had a single stone. Stones were more frequently observed in females.
      Bile examination was positive for O. viverrini eggs in 50% of the cases studied.
      Aggregates of calcium bilirubinate precipitates were observed in all cases with
      sludge. Deposition of calcium bilirubinate on the eggshell was visualized by
      special staining. A SEM study demonstrated the presence of the parasite eggs in
      the stones. Numerous crystals, morphologically consistent with calcium
      derivatives and cholesterol precipitates, were seen. CONCLUSION: Northeast
      Thailand has a high prevalence of pigment stones, as observed at the
      cholecystectomy, and liver fluke infestation seems involved in the pathogenesis
      of stone formation.

PMID- 15484309
TI  - Long-term results of graded pneumatic dilatation under endoscopic guidance in
      patients with primary esophageal achalasia.
AB  - AIM: Achalasia is the best known primary motor disorder of the esophagus in which
      the lower esophageal sphincter (LES) has abnormally high resting pressure and
      incomplete relaxation with swallowing. Pneumatic dilatation remains the first
      choice of treatment. The aims of this study were to determine the long term
      clinical outcome of treating achalasia initially with pneumatic dilatation and
      usefulness of pneumatic dilatation technique under endoscopic observation without
      fluoroscopy. METHODS: A total of 65 dilatations were performed in 43 patients
      with achalasia [23 males and 20 females, the mean age was 43 years (range, 19
      73)]. All patients underwent an initial dilatation by inflating a 30 mm balloon
      to 15 psi under endoscopic control. The need for subsequent dilatation was based
      on symptom assessment. A 3.5 cm balloon was used for repeat procedures. RESULTS:
      The 30 mm balloon achieved a satisfactory result in 24 patients (54%) and the 35
      mm ballon in 78% of the remainder (14/18). Esophageal perforation as a short-term
      complication was observed in one patient (2.3%). The only late complication
      encountered was gastroesophageal reflux in 2 (4%) patients with a good response
      to dilatation. The mean follow-up period was 2.4 years (6 mo - 5 years). Of the
      patients studied, 38 (88%) were relieved of their symptoms after only one or two
      sessions. Five patients were referred for surgery (one for esophageal perforation
      and four for persistent or recurrent symptoms). Among the patients whose follow
      up information was available, the percentage of patients in remission was 79%
      (19/24) at 1 year and 54% (7/13) at 5 years. CONCLUSION: Performing balloon
      dilatation under endoscopic observation as an outpatient procedure is simple,
      safe and efficacious for treating patients with achalasia and referral of
      surgical myotomy should be considered for patients who do not respond to medical
      therapy or individuals that do not desire pneumatic dilatations.

PMID- 15484310
TI  - Seasonal variation in the onset of acute pancreatitis.
AB  - AIM: A circannual variation in the onset of several acute diseases, mostly
      dealing with cardiovascular system, has been reported. The present study was to
      verify the possible existence of a seasonal variability in the onset of acute
      pancreatitis. METHODS: All patients consecutively admitted to the Hospital of
      Ferrara, Italy, between January 1998 to December 2002, whose discharge diagnosis
      was acute pancreatitis, were considered. According to the time of admission,
      cases were categorized into twelve 1-mo intervals and in four periods by season.
      chi (2) test for goodness of fit and partial Fourier series were used for
      statistical analysis. RESULTS: During the study period, 549 cases of acute
      pancreatitis were observed. A significant peak of higher incidence was found in
      March-May, both for total population, males and subgroups with and without
      cholelithiasis or alcoholism. Fourier analysis showed the existence of a
      circannual rhythmic pattern with its main peak in March (95% C.L.: February
      April, P = 0.005), and a secondary one in September. Death occurred more
      frequently in December-February, compared to the other periods (P = 0.029), and
      chronobiologic analysis yielded a seasonal peak in November-December (P<0.001).
      CONCLUSION: This study shows the existence of a circannual variation in the onset
      of acute pancreatitis, with a significantly higher frequency of events in the
      spring, especially for patients with cholelithiasis or alcoholism. Moreover,
      events occurring during the colder months seem to be characterized by a higher
      mortality rate.

PMID- 15484311
TI  - Composite score of reflux symptoms in diagnosis of gastroesophageal reflux
      disease.
AB  - AIM: To evaluate the significance of the composite score of reflux symptoms in
      the diagnosis of gastroesophageal reflux disease (GERD), and to determine the
      relationship of the composite score with reflux esophagitis (RE) and pathological
      gastroesophageal reflux (PGER). METHODS: Upper digestive endoscopy and /or 24-h
      esophageal pH monitoring were performed in 244 subjects. Of these, 54 were
      consecutive patients attending our clinic with symptoms suggestive of GERD, and
      190 were randomly selected from 2532 respondents who participated in our previous
      general population-based study on GERD. A standardized questionnaire was used to
      classify both the frequency and severity of typical symptoms of GERD (heartburn,
      acid and food regurgitation) using a 4-score scale, and the composite score of
      main reflux symptoms (score index: SI, range from 0 to 18) were calculated for
      every subject. RE was diagnosed according to the Savary-Miller criteria. Subjects
      with abnormal pH-metry (DeMeester score more than 14.7) were considered to have
      PGER. GERD patients were defined as the subjects with RE and/or PGER. RESULTS:
      The sensitivity of SI in the diagnosis of GERD was inversely associated with SI,
      but the specificity tended to increase with increased SI. With the cut-off of 8,
      the SI achieved the highest accuracy of 70.0%, with a sensitivity of 78.6% and a
      specificity of 69.2% in diagnosing GERD, followed by the cut-off of 3, which had
      an accuracy of 62.1%, a sensitivity of 96.4% and a specificity of 34.6%. The
      prevalence of RE, PGER and GERD was strongly associated with increased SI
      (P<0.01), but there was no significant association between the severity of RE and
      SI (P>0.05). Among patients with RE, 69.2% had PGER, and 30.8% were confirmed to
      have negative findings of pH monitoring. Among patients with PGER, 52.9% were
      identified to have RE and 47.1% had negative endscopic findings in esophagus.
      CONCLUSION: According to the composite score of main reflux symptoms, the
      diagnosis of GERD can be made without further tests in most cases. However, 24-h
      esophageal pH monitoring and upper digestive endoscopy are still indicated in
      patients with mild and atypical symptoms.

PMID- 15484313
TI  - A double stapled technique for oesophago-enteric anastomosis.
AB  - AIM: Leakage from oesophageal anastomosis is associated with substantial
      morbidity and mortality. This study presented a novel, safe and effective double
      stapled technique for oesophago-enteric anastomosis. METHODS: The data were
      obtained prospectively from hospital held clinical database. Thirty nine patients
      (26 males, 13 females) underwent upper-gastrointestinal resection between 1996
      and 2000 for carcinoma (n = 36), gastric lymphoma (n = 1), and benign pathology
      (n = 2). Double stapled oesophago-enteric anastomosis was performed in all cases.
      RESULTS: No anastomotic leak was reported. In cases of malignancy, the resected
      margins were free of neoplasm. Three deaths occurred, which were not related to
      anastomotic complications. CONCLUSION: Even though the reported study is an
      uncontrolled one, the technique described is reliable, and effective for
      oesophago-enteric anastomosis.

PMID- 15484312
TI  - Clinical characteristics and prognostic factors of severe acute pancreatitis.
AB  - AIM: To investigate the clinical characteristics and prognostic factors of a
      consecutive series of patients with severe acute pancreatitis (SAP). METHODS:
      Clinical data of SAP patients admitted to our hospital from January 2003 to
      January 2004 were retrospectively reviewed. Collected data included the age,
      gender, etiology, length of hospitalization, APACHE II score at admission, local
      and organ/systemic complications of the patients. RESULTS: Of the 268 acute
      pancreatitis patients, 94 developed SAP. The mean age of SAP patients was 52
      years, the commonest etiology was cholelithiasis (45.7%), the mean length of
      hospitalization was 70 d, the mean score of APACHE II was 7.7. Fifty-four percent
      of the patients developed necrosis, 25% abscess, 58% organ/systemic failure. A
      total of 23.4% (22/94) of the SAP patients died. Respiratory failure was the most
      common organ dysfunction (90.9%) in deceased SAP patients, followed by
      cardiovascular failure (86.4%), renal failure (50.0%). In the SAP patients, 90.9%
      (20/22) developed multiple organ/systemic failures. There were significant
      differences in age, length of hospitalization, APACHE II score and incidences of
      respiratory failure, renal failure, cardiovascular failure and hematological
      failure between deceased SAP patients and survived SAP patients. By multivariate
      logistic regression analysis, independent prognostic factors for mortality were
      respiratory failure, cardiovascular failure and renal failure. CONCLUSION: SAP
      patients are characterized by advanced age, high APACHE II score, organ failure
      and their death is mainly due to multiple organ/systemic failures. In patients
      with SAP, respiratory, cardiovascular and renal failures can predict the fatal
      outcome and more attention should be paid to their clinical evaluation.

PMID- 15484314
TI  - Helicobacter pylori seroprevalence in patients with lung cancer.
AB  - AIM: To assess Helicobacter pylori (H pylori) seroprevalence in a cohort of Greek
      patients with lung cancer. METHODS: Seventy-two lung cancer patients (55 males
      and 17 females, aged 58.2+/-11.7 years) and 68, age and gender-matched, control
      subjects were enrolled. All subjects underwent an enzyme-linked immunosorbent
      assay IgG serologic test for H pylori diagnosis. RESULTS: A correlation between
      age and H pylori IgG level was detected for both lung cancer patients (r = 0.42,
      P = 0.004) and controls (r = 0.44, P = 0.004). Seropositivity for H pylori did
      not differ significantly between patients with lung cancer and controls (61.1% vs
      55.9%, P>0.05). Concerning the mean serum concentration of IgG antibodies against
      H pylori, no significant difference between the two groups was detected (32.6+/
      19.1 vs 27.4+/-18.3 U/mL, P>0.05). CONCLUSION: No significant association between
      H pylori infection and lung cancer was found.

PMID- 15484315
TI  - Patients with brain metastases from gastrointestinal tract cancer treated with
      whole brain radiation therapy: prognostic factors and survival.
AB  - AIM: To identify the prognostic factors with regard to survival for patients with
      brain metastasis from primary tumors of the gastrointestinal tract. METHODS: Nine
      hundred and sixteen patients with brain metastases, treated with whole brain
      radiation therapy (WBRT) between January 1985 and December 2000 at the Department
      of Radiation Oncology, University Hospital Freiburg, were analyzed
      retrospectively. RESULTS: Fifty-seven patients presented with a primary tumor of
      the gastrointestinal tract (esophagus: n = 0, stomach: n = 10, colorectal: n =
      47). Twenty-six patients had a solitary brain metastasis, 31 patients presented
      with multiple brain metastases. Surgical resection was performed in 25 patients.
      WBRT was applied with daily fractions of 2 Gray (Gy) or 3 Gy to a total dose of
      50 Gy or 30 Gy, respectively. The interval between diagnoses of the primary
      tumors and brain metastases was 22.6 mo vs 8.0 mo for patients with primary
      tumors of the colon/rectum vs other primary tumors, respectively (P<0.01, log
      rank). Median overall survival for all patients with brain metastases (n = 916)
      was 3.4 mo and 3.2 mo for patients with gastrointestinal neoplasms. Patients with
      gastrointestinal primary tumors presented significantly more often with a
      solitary brain metastasis than patients with other primary tumors (P<0.05, log
      rank). In patients with gastrointestinal neoplasms (n = 57), the median overall
      survival was 5.8 mo for patients with solitary brain metastasis vs 2.7 mo for
      patients with multiple brain metastases (P<0.01, log-rank). The median overall
      survival for patients with a Karnofsky performance status (KPS) >=70 was 5.5 mo
      vs 2.1 mo for patients with KPS <70 (P<0.01, log-rank). At multivariate analysis
      (Cox Model) the performance status and the number of brain metastases were
      identified as independent prognostic factors for overall survival. CONCLUSION:
      Brain metastases occur late in the course of gastrointestinal tumors.
      Pretherapeutic variables like KPS and the number of brain metastases have a
      profound influence on treatment outcome.

PMID- 15484316
TI  - Development and distribution of mast cells and neuropeptides in human fetus
      duodenum.
AB  - AIM: To study the developmental regularities and heterogeneity of mast cells (MC)
      in human fetus duodenum and the distribution and developmental regularities of
      substance P(SP), calcitonin gene-related peptide (CGRP)-immunoreactive (IR)
      peptidergic nerves in fetus duodenum, as well as the relationship between MC, SP
      and CGRP- IR peptidergic nerves. METHODS: Duodena from 21 cases of human fetus
      and one term infant were stained by hematoxylin-eosin (HE), toluidine blue (TB)
      and immunohistochemical avidin-biotinylated peroxidase complex (ABC) method.
      RESULTS: Lobe-shape intestinal villi in duodenum were already developed at the
      twelfth week. At the 21st wk, muscular mucosa appeared gradually, and four layers
      were observed in the wall of duodenum. TB staining showed that the granules in
      the immature MC were pale violet, while the mature MC were strong violet in color
      by TB staining. Connective tissue MC (CTMC) appeared occasionally in submucosa
      and muscular layer of duodenum at the 16th wk. While the mucosa MC (MMC) appeared
      at the 18th wk. At the 22nd wk, both CTMC and MMC were activated, and distributed
      in the surrounding blood vessels and ganglions. The verge of some MC were
      unclear, and showed degranular phenomena. At the 14th wk, SP and CGRP-IR nerve
      fibers and cells appeared in the myenteric and submucous plexuses in small
      intestine, and the responses were turn strongly. Neurons were light to deep
      brown, and nerve fibers were present as varicose and liner profiles. On the
      corresponding site of serial sections, SP and CGRP immunohistochemical reactions
      were coexisted in one nerve fiber or cell. Some of MC showed SP and CGRP-IR
      positive staining. CONCLUSION: There are two heterogeneous kinds of MC in
      duodenum, MMC and CTMC. MC might play an important role in regulating blood
      circulation and sensation.

PMID- 15484317
TI  - Protective effect of rhIL-1beta on pancreatic islets of alloxan-induced diabetic
      rats.
AB  - AIM: To observe the protective effect of rhIL-1beta on pancreatic islets of
      alloxan-induced diabetic rats. METHODS: Protection of rhIL-1beta on pancreatic
      islets of alloxan-induced diabetic rats (n = 5) was demonstrated with methods of
      immunohistochemistry and stereology. The concentration of serum glucose was
      measured by GOD method and that of serum insulin by RIA. RESULTS: The
      concentration of serum glucose increased but that of insulin decreased after
      administration of alloxan(150 mg/kg), and the volume density and numerical
      density of the islets were zero. In rhIL-1beta pretreated rats, although the
      concentration of serum insulin decreased (from 11.9+/-3.0 mIU/L to 6.1+/-1.6
      mIU/L, P<0.05), that of glucose was at normal level compared with the control
      group. As compared with alloxan group, the concentration of serum glucose in rhIL
      1beta pretreated rats decreased (from 19.4+/-8.9 mmol/L to 12.0+/-4.0 mmol/L,
      P<0.05) and the volume density increased(0/L to. 1/L, P<0.05). CONCLUSION: rhIL
      1beta pretreatment may have protective effect on the islets of alloxan-induced
      diabetic rats.

PMID- 15484318
TI  - Three new alternative splicing variants of human cytochrome P450 2D6 mRNA in
      human extratumoral liver tissue.
AB  - AIM: To identify the new alternative splicing variants of human CYP2D6 in human
      extratumoral liver tissue with RT-PCR and sequencing. METHODS: Full length of
      human CYP2D6 cDNAs was amplificated by reverse transcription-polymerase chain
      reaction (RT-PCR) from a human extratumoral liver tissue and cloned into pGEM-T
      vector. The cDNA was sequenced. Exons from 1 to 4 of human CYP2D6 cDNAs were also
      amplificated by RT-PCR from extratumoral liver tissues of 17 human hepatocellular
      carcinomas. Some RT-PCR products were sequenced. Exons 1 to 4 of CYP2D6 gene were
      amplified by PCR from extratumoral liver tissue DNA. Two PCR products from
      extratumoral liver tissues expressing skipped mRNA were partially sequenced.
      RESULTS: One of the CYP2D6 cDNAs had 470 nucleotides from 79 to 548 (3' portion
      of exons 1 to 5' portion of exon 4), and was skipped. Exons 1 to 4 of CYP2D6 cDNA
      were assayed with RT-PCR in 17 extratumoral liver tissues. Both wild type and
      skipped mRNAs were expressed in 4 samples, only wild type mRNA was expressed in 5
      samples, and only skipped mRNA was expressed in 8 samples. Two more variants were
      identified by sequencing the RT-PCR products of exons 1 to 4 of CYP2D6 cDNA. The
      second variant skipped 411 nucleotides from 175 to 585. This variant was
      identified in 4 different liver tissues by sequencing the RT-PCR products. We
      sequenced partially 2 of the PCR products amplified of CYP2D6 exon 1 to exon 4
      from extratumoral liver tissue genomic DNA that only expressed skipped mRNA by RT
      PCR. No point mutations around exon 1, intron 1, and exon 4, and no deletion in
      CYP2D6 gene were detected. The third variant was the skipped exon 3 , and 153 bp
      was lost. CONCLUSION: Three new alternative splicing variants of CYP2D6 mRNA have
      been identified. They may not be caused by gene mutation and may lose CYP2D6
      activity and act as a down-regulator of CYP2D6.

PMID- 15484319
TI  - Effects of endostatin on expression of vascular endothelial growth factor and its
      receptors and neovascularization in colonic carcinoma implanted in nude mice.
AB  - AIM: To investigate the antiangiogenic effects of endostatin on colonic carcinoma
      cell line implanted in nude mice and its mechanism. METHODS: Nude mice underwent
      subcutaneous injection with LS-174t colonic carcinoma cell line to generate
      carcinoma and were randomly separated into two groups. Mice received injection of
      vehicle or endostatin every day for two weeks. After the tumor was harvested, the
      tumor volumes were determined, and the expressions of CD34, VEGF and Flk-1 were
      examined by immunohistochemical method. RESULTS: Tumor volume was significantly
      inhibited in the endostatin group (84.17%) and tumor weight was significantly
      inhibited in the endostatin group (0.197+/-0.049) compared to the control group
      (1.198+/-0.105) (F = 22.56, P = 0.001), microvessel density (MVD) was
      significantly decreased in the treated group (31.857+/-3.515) compared to the
      control group (100.143+/-4.290) (F = 151.62, P<0.001). Furthermore, the
      expression of Flk-1 was significantly inhibited in the treated group (34.29%)
      compared to the control group (8.57%) (chi(2) = 13.745, P = 0.001). However no
      significant decrease was observed in the expression of vascular endothelial
      growth factor (VEGF) between these two groups (chi(2) = 0.119,P = 0.730).
      CONCLUSION: Endostatin can inhibit tumor growth and angiogenesis by blocking
      Vegf/Flk-1 pathway. This experiment provides the theory basis for developing a
      new anti-carcinoma drug through studying the properties of anti-angiogenesis
      inhibitors.

PMID- 15484320
TI  - Proteomic analysis of blood level of proteins before and after operation in
      patients with esophageal squamous cell carcinoma at high-incidence area in Henan
      Province.
AB  - AIM: To characterize the protein files in blood from same patients with
      esophageal squamous cell carcinoma (ESCC) before and after operation at the high
      incidence area for ESCC in Henan Province, China. METHODS: Two-dimensional
      electrophoresis, silver staining and ImageMaster 2-DE analysis software were
      applied to the determination of protein files in the blood obtained from normal
      controls and ESCC patients before and after operation. RESULTS: A total of 655,
      662 and 677 protein spots were identified, respectively, from the normal controls
      and ESCC patients before and after operation. No significant difference in the
      number of protein spots was observed between the normal group and ESCC patients.
      A total of seven protein spots were identified with a dramatic difference among
      the samples before and after operation. Six protein spots were up-regulated and
      one protein spot was down-regulated in the group after operation compared with
      those in normal and before operation. Three protein spots were further
      characterized by matrix-assisted laser desorption/ionization time of flying mass
      spectrometry (MALDI-TOF-MS). The proteins from these three spots were identified
      as serum amyloid A (SAA), amyloid related serum protein and haptoglobin.
      CONCLUSION: Serum amyloid A, amyloid related serum protein and haptoglobin may be
      related with ESCC and/or surgery. The significance of these proteins needs to be
      further characterized. The present study provides informative data for the
      establishment of serum protein profiles related with ESCC.

PMID- 15484321
TI  - Tumor micrometastases in mesorectal lymph nodes and their clinical significance
      in patients with rectal caner.
AB  - AIM: To investigate the number, size, and status of lymph nodes within the
      mesorectum and to explore the prognostic significance of lymph node
      micrometastases in patients with rectal cancer. METHODS: Thirty-one patients with
      rectal cancer undergone total mesorectal excision between October 2001 and
      October 2002 were included. Mesorectal nodes retrieved from the resected
      specimens were detected with a combination of haematoxylin and eosin (HE)
      staining and immunohistochemistry (IHC). The relations between lymph node
      metastases, micrometastases and postoperative recurrence were analyzed. RESULTS:
      A total of 548 lymph nodes were harvested, with 17.7+/-8.2 nodes per case. The
      average number of metastatic nodes in HE-positive patients and micrometastatic
      nodes in IHC-positive patients was 5.2+/-5.1 per case and 2.2+/-1.3 per case,
      respectively. The mean size of all nodes and metastatic nodes was 4.1+/-1.8 mm
      and 5.2+/-1.7 mm in diameter, respectively. The mean size of micrometastatic
      nodes was 3.9+/-1.4 mm in diameter. The size of the majority of mesorectal nodes
      (66.8%), metastatic nodes (52.6%), and micrometastatic nodes (79.5%) was less
      than 5 mm in diameter. During a median follow-up period of 24.6+/-4.7 mo, 5
      patients (16.7%) had recurrence, of them 2 died and 3 survived. Another case died
      of tumor unrelated cause and was excluded. All 5 recurrent cases had 3 or more
      nodes involved, and one of them developed only lymph node micrometastases. The
      mean number of both metastatic and micrometastatic nodes per case differed
      significantly between the recurrent and non-recurrent groups (P<0.01 and P =
      0.01, respectively). CONCLUSION: The majority of lymph nodes, metastatic, and
      micrometastatic lymph nodes within the mesorectum are smaller than 5 mm in
      diameter. The nodal status and the number of lymph nodes involved with tumor
      metastases and micrometastases are related to the rapid postoperative recurrence.

PMID- 15484322
TI  - Possible stem cell origin of human cholangiocarcinoma.
AB  - AIM: To investigate the expression of CD34 and c-kit (receptor of stem cell
      factor) in cholangiocarcinoma. METHODS: Fifteen cases of intrahepatic
      cholangiocarcinoma and 17 cases of extrahepatic cholangiocarcinoma were studied
      in this experiment. Using Envision detection system, paraffin-embedded sections
      of the resected cholangiocarcinoma tissue were stained with antibodies against
      CD34 and c-kit, respectively. The sections were counterstained with hematoxylin,
      and the results were examined under light microscope. Normal tonsil and mammary
      tissues were used as positive controls for CD34 and c-kit, respectively. RESULTS:
      CD34 was positive in all sections, but only in capillary endothelial cells of
      tumor tissue. No cholangiocarcinoma cells were positive for CD34. In one case of
      extrahepatic cholangiocarcinoma, a few tumor cells (about 5%) were immunoreactive
      with c-kit. CONCLUSION: CD34 or c-kit positive cells in liver tissue may
      represent liver stem cells, as they can differentiate into mature biliary cells
      in vitro. The expression of c-kit by some cholangiocarcinoma cells suggests that
      cholangiocarcinoma might originate from liver stem cells. However, other
      mechanisms of hepatocarcinogenesis, such as de-differentiation of mature
      cholangiocytes, may also exist.

PMID- 15484323
TI  - Epidemiology of peptic ulcer disease in Wuhan area of China from 1997 to 2002.
AB  - AIM: To describe the epidemiological features of peptic ulcer disease in Wuhan
      area during 1997-2002, to analyze the sex, age and occupation characteristics, as
      well as the geographic distribution of peptic ulcer disease, and to determine the
      effective methods of preventing and controlling peptic ulcer disease. METHODS: In
      the early 1980s, the peptic ulcer disease registry system was established to
      collect the data of peptic ulcer disease in Wuhan area. Here we performed a
      statistically detailed analysis of 4876 cases of peptic ulcer disease during 1997
      2002. RESULTS: The morbidity of peptic ulcer disease between males and females
      was significantly different (chi(2) = 337.9, P<0.001). The majority of peptic
      ulcer diseases were found at the age of 20 to 50 years. Because of different
      occupations, the incidence of peptic ulcer disease was different in different
      areas. CONCLUSION: The incidence of peptic ulcer disease is highly associated
      with sex, age, occupation and geographic environmental factors. By analyzing the
      epidemiological features of peptic ulcer disease, we can provide the scientific
      data for prevention and control of peptic ulcer disease.

PMID- 15484324
TI  - Effect of 2-(3-carboxy-1-oxopropyl) amino-2-deoxy-D-glucose on human esophageal
      cancer cell line.
AB  - AIM: To determine whether 2-(3-carboxy-1-oxopropy1) amino-2-deoxy-D-glucose
      (COPADG), a derivative of D-amino-glucose, inhibited the growth of human
      esophageal cancer cell line Eca-109. METHODS: Effects of COPADG on Eca-109 cells
      cultured in RPMI 1640 medium were examined by a tetrazolium-based colorimetric
      assay (MTT assay). RESULTS: COPADG inhibited the growth of Eca-109 cells in a
      dose- and time-dependent manner; the maximum inhibition rate was 83.75%.
      CONCLUSION: COPADG can directly inhibit the proliferation of Eca-109 cells, which
      may serve as the experimental evidence for development of new drugs for
      esophageal cancer therapy.

PMID- 15484325
TI  - A case of atypical caudate lobe hemangioma mimicking hepatocellular carcinoma: CT
      and angiographic manifestations.
AB  - We report a case of caudate lobe hemangioma with an atypical CT enhancement
      pattern. In the present case, hemangioma exhibited a very subtle discontinuous
      peripheral rim enhancement at the post-enhanced arterial phase, and the
      peripheral enhanced zone had a moderately increased enhancement degree and with
      widened enhancement thickness during the portal-phase and delayed-phase. The slow
      enhancement rate for this caudate lobe hemangioma was due to sluggish perfusion
      by the small feeding arteries of caudate lobe branches as demonstrated by
      angiography.

PMID- 15484326
TI  - Recurrence of hepatocellular carcinoma with rapid growth after spontaneous
      regression.
AB  - We report an 80-year-old man who presented with spontaneous regression of
      hepatocellular carcinoma (HCC). He complained of sudden right flank pain and low
      grade fever. The level of protein induced by vitamin K antagonist (PIVKA)-II was
      1 137 mAU/mL. A computed tomography scan in November 2000 demonstrated a low
      density mass located in liver S4 with marginal enhancement and a cystic mass of
      68 mmX55 mm in liver S6, with slightly high density content and without marginal
      enhancement. Angiography revealed that the tumor in S4 with a size of 25 mmX20 mm
      was a typical hypervascular HCC, and transarterial chemoembolization was
      performed. However, the tumor in S6 was hypovascular and atypical of HCC, and
      thus no therapy was given. In December 2000, the cystic mass regressed
      spontaneously to 57 mmX44 mm, and aspiration cytology revealed bloody fluid, and
      the mass was diagnosed cytologically as class I. The tumor in S4 was treated
      successfully with a 5 mm margin of safety around it. The PIVKA-II level
      normalized in February 2001. In July 2001, the tumor regressed further but
      presented with an enhanced area at the posterior margin. In November 2001, the
      enhanced area extended, and a biopsy revealed well-differentiated HCC, although
      the previous tumor in S4 disappeared. Angiography demonstrated two tumor stains,
      one was in S6, which was previously hypovascular, and the other was in S8.
      Subsequently, the PIVKA-II level started to rise with the doubling time of 2-3
      wk, and the tumor grew rapidly despite repeated transarterial embolization with
      gel foam. In February 2003, the patient died of bleeding into the peritoneal
      cavity from the tumor that occupied almost the entire right lobe. Considering the
      acute onset of the symptoms, we speculate that local ischemia possibly due to
      rapid tumor growth, resulted in intratumoral bleeding and/or hemorrhagic
      necrosis, and finally spontaneous regression of the initial tumor in S6.

PMID- 15484328
TI  - Redox cycling of coenzyme Q9 as a new measure of plasma reducing power.

PMID- 15484327
TI  - Neuroimaging in stroke recovery: a position paper from the First International
      Workshop on Neuroimaging and Stroke Recovery.

PMID- 15484329
TI  - Demonstration of an alternative approach to immuno-PCR.

PMID- 15484330
TI  - Quantitative, rapid europium(III) nanoparticle-label-based all-in-one dry-reagent
      immunoassay for thyroid-stimulating hormone.

PMID- 15484331
TI  - Photo-removable protecting groups for in situ DNA microarray synthesis.

PMID- 15484332
TI  - Mass spectrometric analysis of protein markers for ovarian cancer.

PMID- 15484333
TI  - Nucleic acid testing using surface plasmon resonance fluorescence detection.

PMID- 15484334
TI  - Homogeneous time-resolved fluorescence quenching assay (TruPoint) for nucleic
      acid detection.

PMID- 15484335
TI  - Clinical evaluation of an algorithm for short sample detection on a multi-analyte
      panel using a point-of-care analyzer.

PMID- 15484336
TI  - Use of computer simulation to study impact of increasing routine test volume on
      turnaround times of STAT samples on ci8200 integrated chemistry and immunoassay
      analyzer.

PMID- 15484338
TI  - Useful estimates of assay performance from small data sets.

PMID- 15484337
TI  - Microarray-based approach for high-throughput genotyping of single-nucleotide
      polymorphisms with layer-by-layer dual-color fluorescence hybridization.

PMID- 15484339
TI  - [Diagnosis and treatment of hypogonadism in adult males].
AB  - Hypogonadism in men is defined as endocrine dysfunction of the testes, and due to
      reduced serum testosterone levels leads to symptoms of testosterone deficiency.
      Depending on the location of disruption in the endocrinological cycle,
      hypogonadism is classified as primary, secondary, or tertiary. In primary
      hypogonadism, the production of testosterone in the Leydig's cells of the testes
      does not function properly. Serum LH concentrations are elevated in the sense of
      counterregulation (hypergonadotropic hypogonadism). In secondary hypogonadism, LH
      secretion (and usually also FSH) from the hypophysis is impaired so that Leydig's
      cells are not stimulated, while in tertiary hypogonadism the hypothalamus is
      damaged. The clinical course in cases of reduced serum testosterone levels is
      determined essentially by the point in time when hypogonadism becomes manifest.
      Delayed puberty, eunuchoid stature, and underdeveloped secondary sex
      characteristics suggest prepubertal onset of hypogonadism.

PMID- 15484340
TI  - Practice parameters for colon cancer.

PMID- 15484341
TI  - Stapled transanal rectal resection for outlet obstruction: a prospective,
      multicenter trial.
AB  - PURPOSE: This prospective, multicenter trial was designed to assess the safety
      and effectiveness of a novel technique in the treatment of outlet obstruction
      caused by the combination of intussusception and rectocele by using a double
      transanal, 33-mm circular stapler. METHODS: From January to October 2001, 90
      patients with outlet obstruction were operated on and followed (mean, 16.3 +/-
      2.9 months) by the validated Constipation Scoring and Continence Grading Systems,
      clinical examination, defecography, and anorectal manometry. Anal ultrasound also
      was performed in 58 multiparous patients. RESULTS: Operative time and hospital
      stay were short (mean, 43.3 +/- 8.7 minutes and 2.1 +/- 0.8 days, respectively),
      and postoperative pain was minimal. The mean time to resume normal activity was
      10.2 +/- 4.5 days. Complications were 17.8 percent fecal urgency, 8.9 percent
      incontinence to flatus, 5.5 percent urinary retention, 4.4 percent bleeding, 3.3
      percent anastomotic stenosis, and 1.1 percent pneumonia. All constipation
      symptoms significantly improved (P < 0.001) without worsening of anal continence.
      No patient complained of dyspareunia. At postoperative defecography, all patients
      had a double incisure of the lower rectal outline in the site of anastomosis,
      with the disappearance of both intussusception and rectocele. Anal pressure was
      not significantly modified, whereas rectal compliance was restored (P < 0.05). No
      lesions of anal sphincters caused by the operation were found in multiparous
      patients. The outcome at one year was excellent in 48 of 90 patients, good in 33,
      fairly good in 5, and poor in 4. CONCLUSIONS: This novel technique seems to be
      safe and effective in the treatment of outlet obstruction caused by the
      combination of intussusception and rectocele. Randomized trials are required to
      confirm these findings.

PMID- 15484342
TI  - Perineal descent and levator ani hernia: a dynamic magnetic resonance imaging
      study.
AB  - PURPOSE: Patients with symptomatic pelvic organ prolapse often have multifocal
      pelvic floor defects that are not always evident of physical examination. In this
      study, dynamic magnetic resonance imaging of symptomatic patients with pelvic
      floor prolapse demonstrated unsuspected levator ani hernia. This study was
      designed to identify any specific symptoms and/or physical findings associated
      with these hernias. METHODS: Eighty consecutive patients with pelvic organ
      prolapse, fecal and/or urinary incontinence, or chronic constipation received
      standardized questionnaires, physical examination, and dynamic magnetic resonance
      imaging. Fisher's exact test was used to compare symptoms and examination
      findings between patients with or without levator ani hernia. RESULTS: Twelve
      patients (15 percent) were found to have unilateral (n = 8) or bilateral (n = 4)
      levator ani hernias on dynamic magnetic resonance imaging. No one specific
      symptom was directly associated with the presence of a levator ani hernia.
      Furthermore, levator ani hernias were not found more frequently in patients with
      previous pelvic floor surgery. Perineal descent on physical examination was
      associated with the finding of a levator ani hernia in nine patients (P = 0.02).
      Although not statistically significant, there was a trend toward a lower
      incidence of levator ani hernia in females using estrogen replacement therapy (P
      = 0.06). CONCLUSIONS: Patients with symptomatic pelvic organ prolapse and
      perineal descent on physical examination may have a levator ani hernia. Although
      the significance of levator ani hernia needs to be determined, the recurrence
      rate after the surgical management of pelvic organ prolapse remains unacceptably
      high, and ongoing investigation of all associated abnormalities is warranted.

PMID- 15484343
TI  - Outcome of HIV-infected patients with invasive squamous-cell carcinoma of the
      anal canal in the era of highly active antiretroviral therapy.
AB  - PURPOSE: Before the development of highly active antiretroviral therapy for the
      treatment of HIV infection, HIV patients diagnosed with invasive squamous-cell
      carcinoma of the anal canal carried a very poor prognosis. This study was
      designed to determine the outcome in a similar group of patients in the era of
      highly active antiretroviral therapy. METHODS: HIV-positive patients treated for
      invasive squamous-cell carcinoma of the anal canal at the University of Texas
      Medical Center affiliated hospitals from 1980 to 2001 were identified from
      operative data and cancer registries. We reviewed these records and collected
      data regarding age, CD4 count, highly active antiretroviral therapy, cancer
      treatment, complications, and survival. The patients were divided into two groups
      based on the presence or absence of highly active antiretroviral therapy and
      compared using a Kaplan-Meier approach. RESULTS: Fourteen patients with HIV and
      invasive squamous-cell carcinoma of the anal canal were identified. Six were in
      the prehighly active antiretroviral therapy group and eight in the highly active
      antiretroviral therapy group. All were considered for treatment with chemotherapy
      and radiation. In the prehighly active antiretroviral therapy group, one patient
      refused therapy and three were unable to complete the squamous-cell carcinoma
      therapy as planned because of complications. Four of eight highly active
      antiretroviral therapy patients were unable to complete the squamous-cell
      carcinoma therapy as planned. The prehighly active antiretroviral therapy
      patients had a mean age of 40 years and a mean CD4 count of 190 at the time of
      diagnosis. The highly active antiretroviral therapy patients had a mean age of 44
      years and a mean CD4 count of 255 at the time of diagnosis. The 24-month survival
      was 17 percent in the prehighly active antiretroviral therapy group and 67
      percent in the highly active antiretroviral therapy group (P = 0.0524). All six
      patients in the prehighly active antiretroviral therapy group died with active
      squamous-cell carcinoma vs. two in the highly active antiretroviral therapy
      group. Four of the remaining six patients had no evidence of active squamous-cell
      carcinoma at the last follow-up visit. CONCLUSIONS: A review of patients with HIV
      and invasive squamous-cell carcinoma of the anal canal suggests a trend toward a
      higher CD4 count at the time of diagnosis and improved survival in patients
      receiving highly active antiretroviral therapy. In this new era, HIV-positive
      patients should be on highly active antiretroviral therapy. If not, highly active
      antiretroviral therapy should be initiated, and standard multimodality therapies
      for invasive squamous-cell carcinoma of the anal canal are recommended.

PMID- 15484344
TI  - Concurrent vs. staged colectomy and hepatectomy for primary colorectal cancer
      with synchronous hepatic metastases.
AB  - PURPOSE: Resection of hepatic metastases is the preferred treatment for selected
      patients after resection of primary colorectal carcinoma, but timing is
      controversial. This study was designed to compare outcomes of patients receiving
      concurrent resection of hepatic metastases and the primary colorectal tumor with
      those of patients receiving staged resection (within 6 months). METHODS: We
      retrospectively analyzed medical records (1986-1999) of 96 consecutive patients
      with synchronously recognized primary carcinoma and hepatic metastases who
      underwent concurrent (64 patients) or staged (32 patients) colonic and hepatic
      resections performed at our institution. RESULTS: Concurrent and staged groups
      were similar in demographics, tumor grade, stage, preoperative comorbidity
      (cardiac and respiratory), characteristics of hepatic metastases, and single vs.
      multiple lesions. No significant differences were observed between groups
      (concurrent vs. staged) in type of colon resection (P = 0.45) or hepatic
      resection (P = 0.09), overall operative duration (mean, 430 vs. 427 minutes; P =
      0.39), blood loss (mean, 890 vs. 889 ml; P = 0.87), volume of blood products
      transfused (mean, 326 vs. 185 ml; P = 0.08), perioperative morbidity (53 vs. 41
      percent; P = 0.25), disease-free survival from date of hepatectomy (median, 13
      vs. 13 months; P = 0.53), or overall survival from date of hepatectomy (median,
      27 vs. 34 months; P = 0.52). There was no operative mortality. Overall duration
      of hospitalization was significantly shorter for concurrent than for staged
      resection (mean, 11 vs. 22 days; P < or = 0.001). CONCLUSIONS: Concurrent
      colectomy and hepatectomy is safe and more efficient than staged resection and
      should be the procedure of choice for selected patients in medical centers with
      appropriate capacity and experience.

PMID- 15484345
TI  - Can magnetic resonance imaging predict circumferential margins and TNM stage in
      rectal cancer?
AB  - INTRODUCTION: This study was designed to assess whether preoperative magnetic
      resonance imaging scans were able to predict 1) pathologic tumor and node stage,
      and 2) those patients with a pathologically clear circumferential resection
      margin. METHODS: Patients with histologically proven carcinoma of the rectum were
      staged preoperatively using magnetic resonance imaging. Histologic specimens from
      patients undergoing mesorectal excision were reported according to the Royal
      College of Pathologists minimum dataset. Agreement between radiologic staging of
      tumor, local lymph nodes and circumferential resection margin involvement, and
      pathologic reporting was assessed by means of the Kappa statistic. RESULTS: After
      exclusions (10 radiotherapy, 3 failed scans, 10 no surgery, 9 local surgery), 40
      patients remained. Magnetic resonance imaging correctly staged the tumor in 20
      patients, understaged in 12, and overstaged in 8. Statistically, there was poor
      correlation between pathologic and radiologic tumor staging (Kappa, 0.18; 95
      percent confidence interval, -0.13 to 0.42). Magnetic resonance imaging correctly
      staged node status in 27 patients, overstaged in 9, and understaged in 4.
      Statistically, there was poor correlation between pathologic and radiologic node
      staging (Kappa, 0.38; 95 percent confidence interval, 0.08-0.64). Magnetic
      resonance imaging correctly reported the status of the circumferential resection
      margin in 39 patients and understaged 1. Statistically, there was good
      correlation between pathologic and radiologic reporting of circumferential
      resection margin involvement (Kappa, 0.66; 95 percent confidence interval, 0.03
      1). CONCLUSIONS: Preoperative magnetic resonance imaging scans provide poor
      predictive data as to subsequent pathologic tumor and node stage. Preoperative
      magnetic resonance imaging does produce reliable prediction of clear
      circumferential resection margins and provides valuable information in assessing
      whether patients can proceed to surgery without the need for preoperative
      radiotherapy.

PMID- 15484346
TI  - Value of rectal ultrasound in predicting staging and outcome in patients with
      rectal adenocarcinoma.
AB  - PURPOSE: Transrectal ultrasonography is considered the best method to stage
      rectal cancer, and thus the need for preoperative radiotherapy. This
      retrospective study was designed to determine the prognostic value of uTN
      classification on survival of patients treated by preoperative radiotherapy and
      surgery. METHODS: A total of 218 patients with proven rectal adenocarcinoma were
      staged by transrectal ultrasonography before treatment. Transrectal
      ultrasonography reports were reviewed for TN classification, quality of
      examinations, and downstaging (pT < uT). RESULTS: Transrectal ultrasonography
      stages were as follows: uT1, n = 2; uT2, n = 61; uT3, n = 145; uT4, n = 10; uN0,
      n = 94; uN+, n = 124. After radiotherapy, based on operative specimen, lesions
      were staged as pT0, n = 27; pT1, n = 20; pT2, n = 60; pT3/4, n = 111; pN0, n =
      160; pN+, n = 58; pM+, n = 10. Downstaging (measured as a reduction in TN level
      determined by transrectal ultrasonography and pathology of resected specimen)
      occurred in 42.6 percent for T and 38.1 percent for N. Five-year overall and
      disease-free survivals were 71.3 and 62.7 percent, respectively (median follow
      up, 62 months). In univariate or multivariate analysis including parameters
      available before treatment, uT and age but not uN were statistically significant
      prognosis factor for overall survival. Patients with TN downstaging had
      significantly better overall survival. In multivariate analysis, including all
      parameters, only age, gender, pT, and pN+ status predicted poor outcome.
      CONCLUSIONS: In patients with rectal adenocarcinoma treated by preoperative
      radiotherapy, uT classification determined by transrectal ultrasonography before
      radiotherapy, pT and pN classification determined after radiotherapy, and tumor
      downstaging were predictors of survival contrary to uN. Only pTN classification,
      age, and gender were independent predictors in multivariate analysis.

PMID- 15484347
TI  - Predicting proximal advanced neoplasms at screening sigmoidoscopy.
AB  - PURPOSE: This study was designed to assess the predictive value for advanced
      proximal neoplasms (cancer, adenoma > or = 10 mm, or villous component > 20
      percent, or severe dysplasia) of the characteristics of distal polyps. METHODS:
      The study was conducted among patients, aged 55 to 64 years, referred for
      colonoscopy in the Italian trial of sigmoidoscopy screening for colorectal
      cancer. Patients reporting a history of colorectal cancer, adenomas, inflammatory
      bowel disease, recent colorectal endoscopy, or two first-degree relatives with
      colorectal cancer were excluded. We compared the prevalence of advanced proximal
      neoplasia in patients with "low-risk" (1-2 tubular adenomas, < 10 mm, with low
      grade dysplasia, or hyperplastic polyp) and in those with "high-risk" (size, > or
      = 10 mm, or > or = 3 adenomas, or villous component > 20 percent, or severe
      dysplasia) polyps in the distal colon. RESULTS: Of 426 patients with polyps > 5
      mm, 29 (6.9 percent) were detected with an advanced proximal neoplasm (including
      4 colorectal cancers). The prevalence of proximal advanced neoplasia was 9.4
      percent among patients with high-risk distal polyps and 2.5 percent among those
      with low-risk lesions (adjusted odds ratio, 3.19; 95 percent confidence interval,
      1.06-9.59). Approximately 40 people with low-risk distal polyps 6 to 9 mm should
      undergo colonoscopy to detect one proximal advanced neoplasm; the corresponding
      number for patients with high-risk distal polyps is 10. CONCLUSIONS: The 2.5
      percent prevalence of proximal advanced neoplasms among people with low-risk 6-mm
      to 9-mm distal polyps is similar to the prevalence observed among people without
      distal polyps. Restricting colonoscopy referral to patients with high-risk distal
      polyps might represent a cost-effective strategy in a screening context.

PMID- 15484348
TI  - The prevalence of fecal incontinence in community-dwelling adults: a systematic
      review of the literature.
AB  - PURPOSE: Reported prevalence estimates for fecal incontinence among community
      dwelling adults vary widely. A systematic review was undertaken to investigate
      the studied prevalence of fecal incontinence in the community and explore the
      heterogeneity of study designs and sources of bias that may explain variability
      in estimates. METHODS: A predetermined search strategy was used to locate all
      studies published that reported the prevalence of fecal incontinence in a
      community-based sample of adults. Data were extracted onto a proforma for
      sampling frame and method, sample size, response rate, definition of fecal
      incontinence used, data-collection method, and prevalence rates. Included studies
      were critically appraised for possible sources of selection bias, information
      bias, and imprecision. RESULTS: A total of 16 studies met the inclusion criteria.
      These could be grouped into definitions of incontinence that included or excluded
      incontinence of flatus. The estimated prevalence of anal incontinence (including
      flatus incontinence) varied from 2 to 24 percent, and the estimated prevalence of
      fecal incontinence (excluding flatus incontinence) varied from 0.4 to 18 percent.
      Only three studies were found to have a study design that minimized significant
      sources of bias, and only one of these used a validated instrument for data
      collection. The prevalence estimate of fecal incontinence from these studies was
      11 to 15 percent. No pooling of estimates was undertaken because there was wide
      variation in study design. CONCLUSIONS: A consensus definition of fecal
      incontinence is needed that accounts for alterations in quality of life. Further
      cross-sectional studies are required that minimize bias in their design and use
      validated self-administered questionnaires.

PMID- 15484349
TI  - Sacral neuromodulation in patients with fecal incontinence: a single-center
      study.
AB  - PURPOSE: Fecal incontinence is a psychologically devastating and socially
      incapacitating condition. Conventional treatment is likely to improve continence
      in many patients; however, there remains a group with persisting symptoms who are
      not amenable for a simple surgical repair. We evaluated the effect of sacral
      neuromodulation in patients with structurally intact sphincters after failure of
      conventional treatment. METHODS: Patients aged 18 to 75 years were evaluated.
      Incontinence was defined as involuntary loss of stool at least once per week,
      which was objectified by completion of a three-week bowel-habits diary during
      ambulatory electrode stimulation at the S3 or S4 foramen. Patients were qualified
      for permanent stimulation when showing a reduction of at least 50 percent in
      incontinence episodes or days. RESULTS: Seventy-five patients (66 females; mean
      age, 52 (range, 26-75) years) were treated. Three patients had partial spinal
      cord injury, two patients a previous low-anterior resection, and nine patients
      had a previous sphincter repair. Evaluation after trial screening showed that 62
      patients (83 percent) had improved continence. Median incontinence episodes per
      week decreased from 7.5 to 0.67 (P < 0.01), median incontinence days per week
      from 4 to 0.5 (P < 0.01). The symptomatic response stayed unchanged after
      implantation of a permanent electrode and pacemaker in 50 patients. After a
      median follow-up of 12 months, this effect could be sustained in 48 patients.
      Anal manometry during stimulation showed no increase of sphincter pressures.
      CONCLUSIONS: Sacral neuromodulation is a feasible treatment option for fecal
      incontinence in patients with structurally intact sphincters.

PMID- 15484350
TI  - Immediate repair of obstetric anal sphincter rupture: medium-term outcome of the
      overlap technique.
AB  - PURPOSE: Overlap sphincteroplasty is gaining popularity in the primary repair of
      obstetric sphincter ruptures. This study was designed to evaluate the medium-term
      outcome of the overlap technique. METHODS: Between August 1997 and October 2001,
      31 consecutive females who were diagnosed with a complete third-degree or fourth
      degree anal sphincter rupture underwent overlap sphincteroplasty immediately
      after delivery. Thirty of the females were followed-up for a median of 24 months.
      The outcome was assessed by clinical examination, anal endosonography, Wexner
      score, and pelvic floor electromyography. RESULTS: Median 24 (range, 12-63)
      months after delivery, 23 females (77 percent) were free of symptoms of anal
      incontinence. Occasional incontinence to flatus and liquid stool occurred in 17
      and 7 percent of patients, respectively. Seven percent of patients had a Wexner
      incontinence score of > 9. The maximum mean resting pressure was 55 (range, 20
      90) mmHg, and the maximum mean incremental squeeze pressure was 37 (range, 14-95)
      mmHg. On anal endosonography, an unrecognized internal sphincter rupture was
      found in one and a failed repair in two females. Overlap of the external
      sphincter was demonstrated in 29 patients (97 percent). One female with anal
      incontinence and persisting external sphincter rupture underwent redo
      sphincteroplasty. CONCLUSIONS: The median-term outcome of primary overlap repair
      for obstetric sphincter rupture is good; however, larger, randomized studies with
      a longer follow-up are needed to evaluate the advantage of this technique over
      the end-to-end technique.

PMID- 15484351
TI  - Long-term outcome of rubber band ligation for symptomatic primary and recurrent
      internal hemorrhoids.
AB  - PURPOSE: Rubber band ligation therapy for symptomatic hemorrhoidal disease has
      been used for many years and is a well-accepted treatment modality, but
      information on long-term outcome is limited. Our goals were to determine safety
      and long-term efficacy of this treatment. METHODS: A retrospective chart review
      of patients undergoing rubber band ligatures for symptomatic internal hemorrhoids
      in a single practice was conducted. Information on presenting symptoms, number of
      bands applied, response to therapy, complications encountered, length of follow
      up, interval to recurrent symptoms when applicable, and subsequent therapy were
      documented. Supplemental information was obtained from telephone follow-up.
      Outcome was categorized as success or failure, in which success was defined as:
      permanent relief of symptoms for follow-up period; marked improvement in
      symptomatology with rare manifestation of bleeding (< or = 1/month); symptom
      relief for a limited period of time (> or = 100 days), and failure was defined
      as: modest improvement (decreased but not relief of symptoms); or no improvement
      in symptoms. RESULTS: A total of 805 patients underwent 2,114 rubber band
      ligatures. Most common presenting symptoms were bleeding in 731 patients (90.8
      percent) and prolapsing in 382 patients (47.5 percent). The median number of
      bands placed was two (range, 1-17). The median time between bandings was 4.7
      (range, 1.1-35.6) weeks. Median follow-up time was 1,204 (range, 14-9,571) days.
      Excluding 104 patients lost to follow-up (never returned after initial
      treatment), success was obtained in 70.5 percent (494/701) and failure in 29.5
      percent (207/701) of patients. Success rates were similar for all degrees of
      hemorrhoids. Hemorrhoidal disease requiring the placement of four or more bands
      was associated with a trend in higher failure rates and greater need for
      subsequent hemorrhoidectomy. Complications per treatment series included bleeding
      (2.8 percent), thrombosed external hemorrhoids (1.5 percent), and bacteremia
      (0.09 percent). Higher bleeding rates were encountered with the use of
      acetylsalicylic acid/nonsteroidal anti-inflammatory drugs and warfarin. Time to
      recurrence was less with subsequent treatment courses. Treatment of recurrent
      symptoms with rubber band ligation resulted in success rates of 73.6, 61.4, and
      65 percent for first, second, and third recurrences respectively. This resulted
      in a cumulative success rate of 80.2 percent for this method of treatment.
      CONCLUSIONS: Rubber band ligatures are safe and effective therapy for symptomatic
      internal hemorrhoids. It can be used to treat all degrees of hemorrhoids with
      similar effectiveness. The likelihood of success is lower if more than four bands
      are needed to eliminate symptoms. The use of acetylsalicylic acid/nonsteroidal
      anti-inflammatory drugs and warfarin is associated with higher bleeding rates.
      Rubber band ligatures for recurrence of symptoms is effective; however, time to
      recurrence is less with subsequent treatments.

PMID- 15484352
TI  - Benefits of hand-assisted laparoscopic restorative proctocolectomy: a comparative
      study.
AB  - PURPOSE: Hand-assisted laparoscopic colectomy is thought to facilitate colonic
      mobilization while maintaining the benefits of laparoscopic surgery. Although
      previous studies of hand-assisted colectomy have focused on segmental colonic
      resection, the use of hand-assisted laparoscopic restorative proctocolectomy has
      not been investigated. This study evaluated the effectiveness of hand-assisted
      laparoscopic approach compared with a conventional laparoscopic method in
      patients undergoing restorative proctocolectomy. METHODS: From a prospective
      database, a consecutive series of patients were identified undergoing
      conventional and hand-assisted laparoscopic restorative proctocolectomy and
      results were compared. Twenty-three patients, comprising 10 hand-assisted and 13
      conventional laparoscopic patients, were identified. Patient characteristics,
      perioperative parameters, and outcomes were assessed. RESULTS: Both groups were
      well matched with no differences in age, gender, body mass index, operative
      indication, diagnosis, comorbidity, or steroid usage. There were no differences
      among incision size between the hand-assisted (8 (range, 8-20) cm) and
      conventional laparoscopic cases (8 (range, 5-10) cm). The median operative time
      was significantly shorter in the hand-assisted group (247 (range, 210-390)
      minutes) compared with the conventional laparoscopic group (300 (range, 240-400)
      minutes; P < 0.01). The length of stay was similar between groups (hand-assisted:
      4 (range, 3-13) days vs. conventional: 6 (range, 4-17) days). Complications
      occurred in four hand-assisted patients (40 percent; 2 ileus, mechanical
      obstruction, and dehydration) and in four patients undergoing conventional
      laparoscopic method (31 percent; 2 anastomotic leak, ileus, and mechanical
      obstruction). CONCLUSIONS: Compared with conventional laparoscopic restorative
      proctocolectomy, the hand-assisted method resulted in a significant reduction in
      operative time without detriment to bowel function, length of stay, or patient
      outcome. The hand-assisted approach to restorative proctocolectomy is likely to
      replace conventional laparoscopic methods as the preferred laparoscopic approach
      for this technically challenging procedure.

PMID- 15484353
TI  - Restorative proctocolectomy for ulcerative colitis complicated by colorectal
      cancer.
AB  - PURPOSE: Restorative proctocolectomy with ileal pouch-anal anastomosis is widely
      accepted as the procedure of choice for patients requiring surgery for chronic
      ulcerative colitis. The role of restorative proctocolectomy in the setting of
      chronic ulcerative colitis complicated by colorectal carcinoma is not clear. This
      study was undertaken to explore the clinical outcomes of chronic ulcerative
      colitis patients with coexisting colorectal carcinoma who underwent restorative
      proctocolectomy. METHODS: A total of 756 patients with chronic ulcerative colitis
      were followed prospectively after restorative proctocolectomy. Forty-five (5.9
      percent) were found to have invasive carcinoma of the colon (n = 31) or rectum (n
      = 14). These patients were followed with special attention to cancer stage,
      adjuvant therapy, oncologic outcome, and functional results after restorative
      proctocolectomy. RESULTS: Twenty-one patients (45.6 percent) had staged surgery
      (colon, 14; rectum, 7). Twenty-seven patients received adjuvant chemotherapy
      (colon, 22; rectum, 5). Fourteen patients (51.8 percent) who received
      chemotherapy were not diverted during this treatment. Two node-positive rectal
      cancer patients had pelvic radiotherapy: one before restorative proctocolectomy
      and one after restorative proctocolectomy. Mean time to restoration of intestinal
      continuity among staged patients did not differ between cancer and noncancer
      patients. Six patients died of metastatic disease (colon, 3; rectum, 3). Five
      deaths occurred among patients with Stage III disease (colon, 3/13, 23.1 percent;
      rectum, 2/3, 66.7 percent). One patient with Stage I cancer at the time of
      restorative proctocolectomy died. Thirty-nine patients are alive without evidence
      of disease at a mean interval from surgery of 76.5 months. Thirty-six patients
      have functioning pelvic pouches. Bowel frequency, continence, and complication
      rates are similar among restorative proctocolectomy patients with and without
      cancer. CONCLUSIONS: Restorative proctocolectomy as a single or staged procedure
      is a viable therapeutic option for selected chronic ulcerative colitis patients
      with associated colorectal cancers. Prognosis seems to be related to cancer
      stage. Adjuvant chemotherapy can safely be given to nondiverted patients.
      Appropriate use of preoperative and postoperative radiotherapy for rectal cancer
      patients who are otherwise candidates for restorative proctocolectomy is unknown.
      Long-term functional results for cancer patients are similar to those seen in
      chronic ulcerative colitis patients without cancer.

PMID- 15484354
TI  - Functional assessment of bacterial colonization in patients with ileal pouch-anal
      anastomosis and Brooke ileostomy.
AB  - PURPOSE: This study was designed to determine whether patients with an ileal
      pouch-anal anastomosis have increased gastrointestinal bacterial colonization as
      assessed functionally compared with patients with Brooke ileostomy and to
      determine the effect of pouch bacterial colonization on pouch function. METHODS:
      Gastrointestinal bacterial colonization in 27 patients with an ileal pouch-anal
      anastomosis and 20 patients with a Brooke ileostomy was assessed using the 14C
      glycocholate and glucose-hydrogen breath tests. Bacterial colonization was
      correlated with pouch function and pouch satisfaction. RESULTS: Patients with
      ileal pouch-anal anastomosis had increased levels of gastrointestinal bacterial
      colonization as measured using the 14C-glycocholate method compared with patients
      with Brooke ileostomy (P = 0.03). Only three patients had a positive result on
      the glucose hydrogen breath test, two patients with ileal pouch-anal anastomosis,
      and one with ileostomy; however, the ileal pouch-anal anastomosis patients did
      have higher levels on this test. Pouch satisfaction and pouch symptoms of urgency
      were not correlated with levels of bacterial colonization, whereas there was a
      nonsignificant trend with continence. CONCLUSIONS: We showed increased levels of
      gastrointestinal bacterial colonization with ileal pouch-anal anastomosis
      compared with Brooke ileostomy. The increase in bacteria is not limited to the
      pouch but also are found in the proximal small bowel. There was no correlation
      between bacterial colonization and urgency, continence, and pouch satisfaction.
      Reasons for this are discussed.

PMID- 15484355
TI  - Intraperitoneal administration of adenosine inhibits formation of abdominal
      adhesions.
AB  - PURPOSE: Previously we demonstrated that peritoneal lavage with high
      concentrations of adenosine (1 mM) provides pharmacologic levels of adenosine in
      the intestines without elevating adenosine levels in the systemic circulation and
      without causing systemic hemodynamic effects (Alimentary Pharmacology &
      Therapeutics 2000; 14:1371-80). Because adenosine can be safely administered into
      the peritoneal cavity, and because it inhibits fibroblast proliferation and
      collagen production and inflammation and enhances angiogenesis, we tested the
      hypothesis that adenosine applied into the abdominal cavity safely and
      effectively reduces formation of abdominal adhesions. METHODS: To test this
      hypothesis, in Sprague-Dawley rats, a window of right parietal peritoneum was
      removed and the cecum was brushed and placed next to the damaged peritoneum.
      After injury, rats received in the abdominal cavity either 20 ml of saline (n =
      12, Saline Group) or 20 ml of 1 mM adenosine (n = 12, Adenosine 1X Group; and n =
      12, Adenosine 4X Group). At 24, 48, and 72 hours after surgery, rats received by
      intraperitoneal injection either 10 ml of saline (Saline Group and Adenosine 1X
      Group) or 10 ml of 1 mM adenosine (Adenosine 4X Group). RESULTS: After 14 days,
      the degree of adhesion formation was scored (0 to 4) by a blinded observer.
      Animals tolerated the adenosine treatments without signs of discomfort or
      distress. The adhesion scores were 2.6 +/- 0.34, 1.7 +/- 0.40, and 0.74 +/- 0.29
      in the Saline, Adenosine 1X, and Adenosine 4X groups, respectively (P = 0.0035,
      Kruskal-Wallis analysis of variance). CONCLUSION: Peritoneal administration of 1
      mM adenosine safely and effectively reduces adhesion formation.

PMID- 15484356
TI  - Physiologic effects of bowel preparation.
AB  - PURPOSE: Despite the universal use of bowel preparation before colonoscopy and
      colorectal surgery, the physiologic effects have not been described in a
      standardized setting. This study was designed to investigate the physiologic
      effects of bowel preparation. METHODS: In a prospective study, 12 healthy
      volunteers (median age, 63 years) underwent bowel preparation with bisacodyl and
      sodium phosphate. Fluid and food intake were standardized according to weight,
      providing adequate calorie and oral fluid intake. Before and after bowel
      preparation, weight, exercise capacity, orthostatic tolerance, plasma and
      extracellular volume, balance function, and biochemical parameters were measured.
      RESULTS: Bowel preparation led to a significant decrease in exercise capacity
      (median, 9 percent) and weight (median, 1.2 kg). Plasma osmolality was
      significantly increased from 287 to 290 mmol kg(-1), as well as increased
      phosphate and urea concentrations, whereas calcium and potassium concentrations
      decreased significantly after bowel preparation. No differences in plasma or
      extracellular volumes were seen. Orthostatic tolerance and balance function did
      not change after bowel preparation. CONCLUSIONS: Bowel preparation has
      significant adverse physiologic effects, which may be attributed to dehydration.
      The majority of these findings is small and may not be of clinical relevance in
      otherwise healthy patients undergoing bowel preparation and following
      recommendations for oral fluid intake.

PMID- 15484357
TI  - Use of vacuum-assisted closure for healing of a persistent perineal sinus
      following panproctocolectomy: report of a case.
AB  - Perineal sinus is a troublesome complication after proctectomy for inflammatory
      bowel disease or rectal cancer. The results from treatment with simple dressings
      with or without surgical debridement are suboptimal. Definitive management may
      require complex operations with muscular or musculocutaneous flaps. Vacuum
      assisted dressings have been used successfully for management of chronic wounds
      and soft tissue defects. This technique was successfully used in the management
      of a perineal sinus, which occurred after proctectomy for rectal cancer
      developing on a background of inflammatory bowel disease and preoperative
      radiotherapy.

PMID- 15484358
TI  - Mucinous cystadenoma of colonic mesentery: report of a case.
AB  - Cystic tumors of the retroperitoneum, omentum, and mesentery are extremely rare
      lesions. We report a case of one such lesion in the mesentery of the left
      hemicolon that was mistaken on imaging to be an ovarian tumor. Development of
      this tumor at this site has been described only twice before in the literature.

PMID- 15484359
TI  - Full-thickness pouch prolapse after restorative proctocolectomy: a potential
      future problem treated by the new technique of external pelvic neorectal
      suspension (the Express procedure).
AB  - Full thickness pouch prolapse following restroative proctocolectomy is an
      uncommon complication but likely to become more frequent as this population of
      patients grows older. Conventional procedures to correct the prolapse may be
      impossible or significantly risk permanent ileostomy formation. The Express
      technique which is relatively minimally invasive, is a perineal procedure which
      elevates and suspends the antero-lateral walls of the prolapsing pouch to the
      external surface of the pelvis, utilizing strips of long lasting collagen.

PMID- 15484360
TI  - Transanal excision of a large rectal polyp assisted by transsacral manipulation
      of the rectum.
AB  - Standard transanal excision of the rectal polyps is curative and is less invasive
      than transsacral resection or low anterior resction, but it is difficult to
      resect tumors that are distant from the anal verge. Moreover, in the case of
      large polyps, the risks of complications, such as hemorrhage or perforation,
      increase because exposure on the oral side of the tumor is poor. If exposure can
      be improved, transanal excision can be performed safely and completely when the
      polyp is large and distant from the anal verge. We used transsacral manual
      assistance to achieve transanal resection of a large tubulovillous adenoma of the
      rectum that was hard to be resected using the traditional transanal approach.

PMID- 15484361
TI  - Ultrasound study of anal fistulas with hydrogen peroxide enhancement.

PMID- 15484363
TI  - ACT UP: enormous worldwide attention to New York demos.
AB  - Hundreds of major newspapers and broadcast media worldwide covered AIDS and debt
      demonstrations around the Republican National Convention in New York.

PMID- 15484362
TI  - ADAP activists needed in all U.S. states and territories.
AB  - Despite recent short-term improvement, the AIDS Drug Assistance Program needs
      activist attention nationally to prevent thousands of Americans from going
      without the treatment they need.

PMID- 15484364
TI  - Medical information from Bangkok conference: clinical care options site.
AB  - An excellent Web site, primarily for medical professionals but freely available
      to anyone, summarizes what doctors need to know from the International AIDS
      Conference in Bangkok, Thailand.

PMID- 15484365
TI  - AIDSVote: election information and activism.
AB  - A coalition of over 200 AIDS organizations is supporting a platform of policies
      for controlling the AIDS epidemic both in the U.S. and globally. It is
      encouraging voter registration, including absentee registration of people with
      AIDS when necessary, so that they will not miss voting due to illness.

PMID- 15484366
TI  - Elections: widespread misinformation on who can vote.
AB  - Due to persistent misinformation about voter qualifications in Pennsylvania, we
      looked up the facts on the official state Web site. Other states face similar
      problems.

PMID- 15484368
TI  - Clinical trials: Philadelphia hospitals combine to form "supersite" and reduce
      delays.
AB  - Major medical research institutions in Philadelphia are working together to allow
      pharmaceutical companies to conduct clinical trials in multiple institutions with
      a single contract and single approval, reducing paperwork and preventing
      unnecessary research delays.

PMID- 15484367
TI  - Empty antibiotic pipeline critically endangers public: IDSA report.
AB  - A huge decrease in the number of fundamentally new antibiotics--driven by
      commercial not scientific problems--seriously threatens public health in the near
      future, as bacteria develop resistance to the existing drugs, and previously
      treatable infections will often be fatal.

PMID- 15484369
TI  - RTV patent under fire.

PMID- 15484370
TI  - NIH: weekly cycles of once-daily ARVs feasible.

PMID- 15484371
TI  - ART effective in prisoners, benefit lost upon release.

PMID- 15484372
TI  - Prevention, planning, resistance, toxicity.  IAPAC sessions--USA. May 20-21,
      2004, Chicago.

PMID- 15484373
TI  - DDW advances HCV knowledge.

PMID- 15484374
TI  - HIV/HCV coinfection cases require special attention. Experts discuss current
      treatments, concerns.
AB  - Patients with both HIV and HCV have more complicated medical issues, including
      screening for liver problems, drug-drug interactions, depression, and potential
      immune suppression, experts say. Although fewer coinfected patients are dying
      since better HIV and HCV treatments have come on the market, coinfection
      continues to cause patients to die prematurely, according to recent research.

PMID- 15484375
TI  - One size doesn't fit all in Hispanic population. Funding changes may cut off some
      programs.
AB  - Organizations targeting Latino populations for HIV services and prevention
      programs have developed strategies specific to very different groups within that
      community. Experts advise providers to be aware of the large amount of variation
      among Hispanics.

PMID- 15484376
TI  - Program finds success reaching crack addicts. Improvements seen on all fronts.
AB  - A new study reports success in reducing risk and improving women's housing and
      employment status after enrollment in a woman-focused HIV intervention program.

PMID- 15484377
TI  - Physicians counsel new patients more effectively. CDC-funded survey highlights
      problem areas.
AB  - The Centers for Disease Control and Prevention is focusing on the role of
      physicians in it prevention for positives initiative, but one survey found the
      available prevention counseling is less than optimal.

PMID- 15484378
TI  - FDA approves treatment for facial fat loss.

PMID- 15484379
TI  - FDA notifications. New web page launched for HIV drug deliberations.
AB  - The FDA now is making it easier to access consolidated records of advisory
      committee meetings.

PMID- 15484380
TI  - Motivational interviewing seeks specific solutions. Interventions shift
      responsibility to the clients.
AB  - Organizers of a four-session HIV prevention for positives program targeting
      Latinos are finding success with motivational interviewing, which allows clients
      to make a decision based on his or her own motivations.

PMID- 15484382
TI  - [Geographic information system, remote sensing technic and epidemiology].

PMID- 15484383
TI  - [About surgical treatment of Crush syndrome].

PMID- 15484384
TI  - [Uses of epidemiological methods in the study of reproductive health].

PMID- 15484385
TI  - Natural or artificial? Cavitating tuberculous disease.

PMID- 15484386
TI  - Poisoned food, poisoned uniforms, and anthrax: or, how guerillas die in war.
AB  - Many people believe that Rhodesia, struggling to maintain minority rule in
      Africa, used chemical and biological weapons against African guerilla armies in
      the liberation war. Clothes and food were routinely poisoned, and Rhodesian
      agents, perhaps in concert with global forces of reaction, caused the largest
      single outbreak of anthrax in modern times. Oral interviews with traditional
      healers and Rhodesians' confessional memoirs of the war suggest that deaths by
      poisoning or disease were not so straightforward, that guerillas and healers and
      doctors struggled to understand not only what caused death but also what kind of
      death a poisoned uniform or poisoned boot was.

PMID- 15484387
TI  - Oral history, subjectivity, and environmental reality: occupational health
      histories in twentieth-century Scotland.
AB  - This essay uses oral histories of dust disease in twentieth-century Scotland to
      illustrate the ways in which such history can illuminate how the working
      environment and work cultures affect workers' bodies and how workers come to
      terms with the ill-health caused by their employment. It emphasizes the agency of
      the interpreter but argues further that oral histories of dust disease in
      twentieth-century Scotland are simultaneously influenced by, and evidence for,
      material conditions. The essay explores the notion that the bodies, not just the
      voices of interviewees, are material testament to health-corroding work
      practices, cultures, and habitat. The focus is the problems caused by the
      inhalation of coal and asbestos dust.

PMID- 15484389
TI  - The 18th Annual North American Cystic Fibrosis Conference. St. Louis, Missouri,
      USA, October 14-17, 2004. Proceedings and abstracts.

PMID- 15484388
TI  - Biological citizenship: the science and politics of Chernobyl-exposed
      populations.
AB  - In the transition out of socialism to market capitalism, bodies, populations, and
      categories of citizenship have been reordered. The rational-technical management
      of group affected by the Chernobyl disaster in Ukraine is a window into this
      contested process. Chernobyl exemplifies a moment when scientific knowability
      collapsed and new maps and categories of entitlement emerged. Older models of
      welfare rely on precise definitions situating citizens and their attributes on a
      cross-mesh of known categories upon which claims rights are based. Here one
      observes how ambiguities related to categorizing suffering created a political
      field in which a state, forms of citizenship, and informal economies were remade.

PMID- 15484390
TI  - ASRM 2004. Abstracts of the 60th Annual Meeting of the American Society for
      Reproductive Medicine. October 16-20, 2004, Philadelphia, Pennsylvania, USA.

PMID- 15484392
TI  - [Ultrasound 2004. Abstracts of the 28th Three-country meeting of the German,
      Austrian, and Swiss Societies of Ultrasound in Medicine. 6-9 October 2004 in
      Hannover].

PMID- 15484391
TI  - Uncertain exposures and the privilege of imperception: activist scientists and
      race at the U.S. Environmental Protection Agency.
AB  - This paper locates the EPA national headquarters within the racialized local
      geography of southwest Washington, D.C. By focusing on the formation of a
      scientist union and the union's struggle to make visible an episode of chemical
      exposure in its own offices, the paper connects the work of racialized privilege
      with the difficulty of proving chemical exposures in the 1980s.

PMID- 15484393
TI  - From Bhopal to the informating of environmentalism: risk communication in
      historical perspective.
AB  - This essay describes the development of information technology and culture in the
      environmental field since the 1980s and how this has led to new understandings of
      risk communication. The essay also describes how environmental information
      systems operate as instruments of power, in the way they configure and provide
      access to knowledge, in the way they manage uncertainty, and in the way they
      build in and project particular modes of subjectivity. The goal is to provide a
      brief yet compelling glimpse into the "informating of environmentalism."

PMID- 15484394
TI  - Medical image. Pneumoconiosis and a pulsatile mass.

PMID- 15484395
TI  - [Abstracts of the 53rd Meeting of the Association of Ophthalmologists of Northern
      Germany. Braunschweig, Germany, 11-12 June 2004].

PMID- 15484396
TI  - The oriental tradition of Paul of Aegina's Pragmateia.

PMID- 15484397
TI  - Are thoracic surgeons ethically obligated to serve as expert witnesses for the
      plaintiff? Con.

PMID- 15484398
TI  - Polonius' effect defective.

PMID- 15484399
TI  - Lavatory humour: two epigrams addressed to sir John Harington.

PMID- 15484400
TI  - Malaria chemotherapy and the "kaleidoscopic" organisation of biomedical research
      during world war II.
AB  - The paper describes the organisational and scientific evolution of the US
      antimalarial program during World War II. This program screened some 14,000
      compounds for antimalarial activity, selected atabrine as the drug of choice in
      1943, and later identified chloroquine as a superior compound. It became,
      arguably, the largest biomedical research effort of the first half of the
      twentieth century, involving chemical and pharmaceutical companies, diverse
      university researchers, and non-profit and government laboratories. Beyond
      scientific research, the innovations of the wartime antimalarial program were
      chiefly in three areas, communication, scale and administration. The program drew
      on resources - intellectual, material and organisational - created in Germany by
      researchers at Bayer, and in the US by the Rockefeller Foundation and Institutes.
      The paper examines the antimalarial program as one of the formative models for
      later programs such as the National Institutes of Health. This account supports
      the claim that wartime work was essential to the development of NIH, if only
      because the confused and faltering structures of the early war years, 1939-1943,
      do not suggest that all the organisational infrastructure for large scale, multi
      centre co-operative research was in place prior to World War II.

PMID- 15484402
TI  - Abstracts from the 8th Scientific Conference of the Charles University Faculty of
      Medicine and University Hospital. 28 January 2004, Hradec Kralove.

PMID- 15484401
TI  - Biology in the chemical industry: scientific approaches to the problem of
      insecticide resistance, 1920s - 1960s.
AB  - This paper examines the intensification of research and development into organic
      and inorganic insecticidal compounds during the first half of the twentieth
      century, and the involvement of biologists within the insecticide industry. It
      attempts to trace the history of resistance research, while highlighting the role
      of the biologist within the chemical industry prior to the biotechnology
      era.Specifically, this paper looks at the reaction of two private companies on
      the finding of resistance to insecticides: Geigy and Bayer. Geigy, who discovered
      the insecticidal properties of DDT, initially attributed resistance to
      ineffective application of insecticides or variable external factors. Only after
      doubling of the amount of DDT had failed to achieve the desired result, did the
      company undertake a biological research programme in an effort to understand
      resistance from a biological - as opposed to chemical - perspective. Ultimately,
      scientists both inside and outside the industry accepted the biological fact of
      resistance and the realisation that chemical control by itself would not be able
      to circumvent an insect population's ability to tolerate lethal dosages of
      chemical insecticides. The shift in the insecticide industry's approach to
      biological research is instructive in understanding how industry can approach
      complex issues.

PMID- 15484403
TI  - Overexpression of cyclin D1 correlates with sensitivity to cisplatin in squamous
      cell carcinoma cell lines of the head and neck.
AB  - OBJECTIVE: Treatment strategies for squamous cell carcinoma of the head and neck
      (SCCHN) are based on the TNM classification. Biological markers that can predict
      the response to therapy have so far not been introduced. The objective of this
      study was to investigate cyclin D1 deregulation relative to sensitivity to
      cisplatin. MATERIAL AND METHODS: This was a laboratory study of 23 established
      University of Michigan SCC cell lines. Chemosensitivity was assessed by means of
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The
      cyclin D1 amplification status was evaluated by real-time polymerase chain
      reaction (PCR; data were verified by differential and conventional PCR) using a
      chromosome 18q microsatellite marker probe (D18S70) as an internal control.
      Cyclin D1 protein expression was tested using Western blotting. RESULTS: Cyclin
      D1 amplification was seen in 9/23 (39%) and cyclin D1 overexpression in 12/19
      (63%) of the cell lines. As expected, all cell lines showing amplification also
      showed overexpression of cyclin D1 (p=0.004; Fisher's exact test). The mean
      cisplatin concentration inhibiting growth of 50% of the cells (ID50) was 9.8
      microM in all cell lines (range 2.7-36.7 microM). Five of nine cell lines showing
      cyclin D1 amplification were highly sensitive to cisplatin (ID50 3-4.8 microM)
      and the remaining four revealed intermediate sensitivity. Five cell lines that
      strongly overexpressed cyclin D1 protein responded better to cisplatin than cell
      lines that showed any other expression (ID50 5.1 vs 11.2 microM; p=0.025;
      Student's t-test). CONCLUSIONS: This in vitro study suggests that overexpression
      of cyclin D1 is associated with a good response to cisplatin in SCC cell lines.
      Our results support the hypothesis that overexpression of cyclin D1 is one of the
      molecular factors that can be used to predict sensitivity to chemotherapy, thus
      enabling individualization of treatment of head and neck cancer.

PMID- 15484404
TI  - Proceedings of the 16th Internordic Symposium of the Nordic Committee for
      Veterinary Scientific Cooperation (NKVet) on Animal Organs to Save Human Lives.
      Gardermoen, Norway, 11-12 October 2002.

PMID- 15484405
TI  - Networks of innovation or networks of opportunity? The making of the Spanish
      antibiotics industry.
AB  - The pharmaceutical industry is a typically research-intensive, first world
      industry. This article seeks to explain why it has been so difficult for late
      industrialised nations to reproduce the networks of innovation on which the
      design and manufacturing of new drugs has historically based, and why alternative
      concepts are needed in order to understand the dynamics of science-based
      industries in emerging countries. The article analyses the development of the
      Spanish antibiotics industry, build after the World War II under the strong
      influence of the new international order and Spain's political framework,
      academic traditions and business groups. Focusing on the long-term relationships
      established between two Spanish companies (Antibioticos SA and Compania Espanola
      de Penicilina y Antibioticos, CEPA), their American technological partners
      (Schenley and Merck), and their social and scientific environment, the article
      identifies networks of opportunity as the key institutional arrangement of this
      new industry in Spain. Opportunity (as opposed to innovation) networks are thus
      proposed to conceptualise the development of technologically complex industries
      in the European periphery.

PMID- 15484406
TI  - Dynamics of pharmacy regulation in Denmark, 1932-1994: a study of profession
      state relations.

PMID- 15484407
TI  - Chemistry and medicine: the NIH division of chemistry, 1905-1947.

PMID- 15484408
TI  - Civil war pharmacy and medicine: comparisons and contexts.

PMID- 15484409
TI  - Was phrenology a reform science? Towards a new generalization for phrenology.

PMID- 15484410
TI  - Genetic components of lactose intolerance and community frequency.

PMID- 15484411
TI  - Infarction induced ventricular remodeling.

PMID- 15484412
TI  - The ideal human heart valve substitute: 50 years between perceptions and
      realities. September 2003, Naples, Italy. Meeting proceedings.

PMID- 15484413
TI  - Coccygodynia: evaluation and management.

PMID- 15484414
TI  - [Incidentaloma of the adrenal gland: disputable points of diagnosis and surgical
      policy].

PMID- 15484415
TI  - [Multiple chondromatous hamartomas of the lungs].

PMID- 15484416
TI  - H.A. Barker.

PMID- 15484418
TI  - David Ezra Green.

PMID- 15484417
TI  - Robert M. Berne.

PMID- 15484419
TI  - James Gerald Hirsch.

PMID- 15484420
TI  - Horace Winchell Magoun.

PMID- 15484421
TI  - Sanford Louis Palay.

PMID- 15484422
TI  - [Johanniskraut. Hypericum perforatum L.].

PMID- 15484423
TI  - Neointimal vascularization and intimal thickening in response to self-expanding
      stents: a swine model.
AB  - BACKGROUND: Neovascularization has been suggested as a biological response to
      vessel injury and associated with restenosis. Self-expanding (SE) stents generate
      a lasting force on the arterial wall and may lead to an increased arterial
      response with time. OBJECTIVES: To characterize the process of neovascularization
      with SE stents, and to correlate it with vascular injury, inflammation and
      intimal proliferation. METHODS: Sixty-nine SE stents were im-planted in 37 non
      atherosclerotic pigs.Detailed, multisection histological examination was
      performed at 15 days, 1, 3 and 6 months post-deployment. Neo-vascularization in
      addition to other histologic parameters where determined and scored. RESULTS:
      Intravascular-ultrasound-based average vessel diameter was 3.3 +/- 0.04 mm; stent
      size was 3.75 +/- 0.35 mm leading to an oversizing ratio of 1.14 +/- 0.15.
      Intimal thickness (IT), inflammatory score (IFS) and vascularization score(VAS)
      reached peak values at three months (IT = 344 +/- 202 1m, IFS = 0.91 +/- 0.5, and
      VAS = 1.56 +/- 0.8). In contrast,the injury score (INS) continued to increase at
      all time-points, with maximum value at six months (INS = 1.6 +/- 0.7). Both
      vascularization and inflammation indices increased with an increase in the injury
      score (p < 0.01). When vessels were divided according to vascularization score
      (VAS <1.5 and >1.5) there was a significant difference in IT. CONCLUSION:
      Neovascularization in response to SE stents is a time-dependent phenomenon and
      interacts with injury and inflammation. The remodeling of the vessel wall caused
      by the sustained force of the SE stent on the arterial wall enhances the
      formation of neovascularization. Neointimal formation is related to the degree of
      neovascularization.

PMID- 15484424
TI  - Extrahepatic biliary atresia.

PMID- 15484425
TI  - Pseudolesion in left lobe of the liver due to superior vena cava syndrome.

PMID- 15484426
TI  - Guest editorial: Introduction to the special section on pervasive healthcare.

PMID- 15484427
TI  - A new research challenge: persuasive technology to motivate healthy aging.
AB  - Healthcare systems in developed countries are experiencing severe financial
      stress as age demographics shift upward, leading to a larger percentage of older
      adults needing care. One way to potentially reduce or slow spiraling medical
      costs is to use technology, not only to cure sickness, but also to promote
      wellness throughout all stages of life, thereby avoiding or deferring expensive
      medical treatments. Ubiquitous computing and context-aware algorithms offer a new
      healthcare opportunity and a new set of research challenges: exploiting emerging
      consumer electronic devices to motivate healthy behavior as people age by
      presenting "just-in-time" information at points of decision and behavior.

PMID- 15484428
TI  - The use of computer vision in an intelligent environment to support aging-in
      place, safety, and independence in the home.
AB  - This paper discusses the use of computer vision in pervasive healthcare systems,
      specifically in the design of a sensing agent for an intelligent environment that
      assists older adults with dementia during an activity of daily living. An
      overview of the techniques applied in this particular example is provided, along
      with results from preliminary trials completed using the new sensing agent. A
      discussion of the results obtained to date is presented, including technical and
      social issues that remain for the advancement and acceptance of this type of
      technology within pervasive healthcare.

PMID- 15484429
TI  - Unobtrusive monitoring of computer interactions to detect cognitive status in
      elders.
AB  - The U.S. has experienced a rapid growth in the use of computers by elders. E
      mail, Web browsing, and computer games are among the most common routine
      activities for this group of users. In this paper, we describe techniques for
      unobtrusively monitoring naturally occurring computer interactions to detect
      sustained changes in cognitive performance. Researchers have demonstrated the
      importance of the early detection of cognitive decline. Users over the age of 75
      are at risk for medically related cognitive problems and confusion, and early
      detection allows for more effective clinical intervention. In this paper, we
      present algorithms for inferring a user's cognitive performance using monitoring
      data from computer games and psychomotor measurements associated with keyboard
      entry and mouse movement. The inferences are then used to classify significant
      performance changes, and additionally, to adapt computer interfaces with tailored
      hints and assistance when needed. These methods were tested in a group of elders
      in a residential facility.

PMID- 15484430
TI  - The installation and support of internationally distributed equipment for people
      with dementia.
AB  - This paper describes the evaluation and support of assistive technology designed
      to increase the independence of people with dementia. Devices were evaluated by
      people with dementia in their own homes. Working with and supporting people with
      dementia requires relational skills not normally needed by installers and
      technical supporters.

PMID- 15484431
TI  - Multimodal and ubiquitous computing systems: supporting independent-living older
      users.
AB  - We document the rationale and design of a multimodal interface to a
      pervasive/ubiquitous computing system that supports independent living by older
      people in their own homes. The Millennium Home system involves fitting a
      resident's home with sensors--these sensors can be used to trigger sequences of
      interaction with the resident to warn them about dangerous events, or to check if
      they need external help. We draw lessons from the design process and conclude the
      paper with implications for the design of multimodal interfaces to ubiquitous
      systems developed for the elderly and in healthcare, as well as for more general
      ubiquitous computing applications.

PMID- 15484432
TI  - An implantable telemetry platform system for in vivo monitoring of physiological
      parameters.
AB  - This paper describes a microcontroller-based multichannel telemetry system,
      suitable for in vivo monitoring of physiological parameters. The device can
      digitalize and transmit up to three analog signals coming from different sensors.
      The telemetry transmission is obtained by using a carrier frequency of 433.92 MHz
      and an amplitude-shift keying modulation. The signal data rate is 13 kb/s per
      channel. The digital microcontroller provides good flexibility and interesting
      performance, such as the threshold monitoring, the transmission error detection,
      and a low power consumption, thanks to the implementation of a sleep mode. The
      small overall size (less than 1 cm3), the power density compatible with current
      regulations for the design of implantable devices, and the dedicated packaging
      make the system suitable for in vivo monitoring in humans. The design,
      fabrication, operation, packaging, and performance of the system are described in
      this paper. An in vivo pressure monitoring case study is described as well.

PMID- 15484433
TI  - Integrating context-aware public displays into a mobile hospital information
      system.
AB  - Hospitals are convenient settings for deployment of ubiquitous computing
      technology. Not only are they technology-rich environments, but their workers
      experience a high level of mobility resulting in information infrastructures with
      artifacts distributed throughout the premises. Hospital information systems
      (HISs) that provide access to electronic patient records are a step in the
      direction of providing accurate and timely information to hospital staff in
      support of adequate decision-making. This has motivated the introduction of
      mobile computing technology in hospitals based on designs which respond to their
      particular conditions and demands. Among those conditions is the fact that worker
      mobility does not exclude the need for having shared information artifacts
      particular locations. In this paper, we extend a handheld-based mobile HIS with
      ubiquitous computing technology and describe how public displays are integrated
      with handheld and the services offered by these devices. Public displays become
      aware of the presence of physicians and nurses in their vicinity and adapt to
      provide users with personalized, relevant information. An agent-based
      architecture allows the integration of proactive components that offer
      information relevant to the case at hand, either from medical guidelines or
      previous similar cases.

PMID- 15484434
TI  - Personal health information management system and its application in referral
      management.
AB  - We developed a web-based personal health record (PHR) that can be used by
      patients to collect and manage their health information (e.g., medical history,
      past surgeries, medications, and allergies), to request self-referrals, and to
      store a record of their consultations. The PHR also includes a messaging system
      that can be structured into the workflow of referral management as well as
      allowing more general communications. A preliminary study was conducted with 61
      patients. Thirty-two patients completed a survey in which 85% of respondents were
      satisfied with the usability and 94% were satisfied with the overall online
      referral process. The consulting physicians were satisfied with the content of
      subjects' personal health information and referral problem descriptions and found
      the information detailed enough to triage all requested referrals. Patients,
      physicians, and patient care coordinators reported that their communications were
      enhanced by the system and found the messaging component convenient to use.

PMID- 15484435
TI  - A dynamic clinical dental relational database.
AB  - The traditional approach to relational database design is based on the logical
      organization of data into a number of related normalized tables. One assumption
      is that the nature and structure of the data is known at the design stage. In the
      case of designing a relational database to store historical dental
      epidemiological data from individual clinical surveys, the structure of the data
      is not known until the data is presented for inclusion into the database. This
      paper addresses the issues concerned with the theoretical design of a clinical
      dynamic database capable of adapting the internal table structure to accommodate
      clinical survey data, and presents a prototype database application capable of
      processing, displaying, and querying the dental data.

PMID- 15484436
TI  - Multidimensional text classification for drug information.
AB  - This paper proposes a multidimensional model for classifying drug information
      text documents. The concept of multidimensional category model is introduced for
      representing classes. In contrast with traditional flat and hierarchical category
      models, the multidimensional category model classifies each document using
      multiple predefined sets of categories, where each set corresponds to a
      dimension. Since a multidimensional model can be converted to flat and
      hierarchical models, three classification approaches are possible, i.e.,
      classifying directly based on the multidimensional model and classifying with the
      equivalent flat or hierarchical models. The efficiency of these three approaches
      is investigated using drug information collection with two different dimensions:
      1) drug topics and 2) primary therapeutic classes. In the experiments, k-nearest
      neighbor, naive Bayes, and two centroid-based methods are selected as
      classifiers. The comparisons among three approaches of classification are done
      using two-way analysis of variance, followed by the Scheffe's test for post hoc
      comparison. The experimental results show that multidimensional-based
      classification performs better than the others, especially in the presence of a
      relatively small training set. As one application, a category-based search engine
      using the multidimensional category concept was developed to help users retrieve
      drug information.

PMID- 15484437
TI  - Perceptually tuned JPEG coder for echocardiac image compression.
AB  - In this work, we propose an efficient framework for compressing and displaying
      medical images. Image compression for medical applications, due to available
      Digital Imaging and Communications in Medicine requirements, is limited to the
      standard discrete cosine transform-based joint picture expert group. The
      objective of this work is to develop a set of quantization tables (Q tables) for
      compression of a specific class of medical image sequences, namely echocardiac.
      The main issue of concern is to achieve a Q table that matches the specific
      application and can linearly change the compression rate by adjusting the gain
      factor. This goal is achieved by considering the region of interest, optimum bit
      allocation, human visual system constraint, and optimum coding technique. These
      parameters are jointly optimized to design a Q table that works robustly for a
      category of medical images. Application of this approach to echocardiac images
      shows high subjective and quantitative performance. The proposed approach
      exhibits objectively a 2.16-dB improvement in the peak signal-to-noise ratio and
      subjectively 25% improvement over the most useable compression techniques.

PMID- 15484438
TI  - A database for therapy evaluation in neurological disorders: application in
      epilepsy.
AB  - Due to the high diversity of cases and the variety of treatment modalities, the
      information to be managed and processed in therapy evaluation is excessive in
      many neurological diseases. Additionally, in order to gain more insight into, not
      only the disorders, but also the applied therapies, more objectivity is requested
      in clinical practice. Therefore, in this study, a database system is designed for
      assisting therapy evaluation in neurological diseases. A sample implementation is
      accomplished for structuring and managing the information accessible for
      different treatment modalities available for epilepsy. The first application of
      the developed database system for clinical use in epilepsy is tested with
      selected quantitative parameters extracted from electrophysiological signals of
      epilepsy patients who receive neurotherapy as a complementary treatment to the
      pharmacological therapy, as well as of voluntary control subjects. The system
      contributes to the automation of statistical analysis for therapy planning,
      monitoring, and evaluation. It is extendible for other disorders such as
      attention deficit hyperactivity disorder, depression, and sleep disorders.

PMID- 15484439
TI  - A novel algorithm for computer-assisted measurement of cervical length from
      transvaginal ultrasound images.
AB  - The cervical length measured by transvaginal ultrasound is a proven clinical tool
      for predicting premature birth. The standard manual measurement of the cervix is
      limited by variability in the technique. In this research, we develop the first
      computer algorithm that is able to identify the anatomic landmarks of the cervix
      on a transvaginal ultrasound image and determine the standard cervical length.
      The system is composed of four stages: The first stage is adaptive speckle
      suppression using variable length sticks algorithm. The second stage is the
      location of the internal cervical opening or "os" using a region-based
      segmentation. The third stage is delineation of the cervical canal. The fourth
      stage uses gray level summation patterns and prior knowledge to first localize
      the tissue boundary of the external cervix, and then use a template to determine
      the specific location of the external os. The cervical length is determined and
      calculated to image scale. To validate the proposed algorithm, 101 cervical
      ultrasound images were selected from a series of 37 examinations performed on 17
      patients over an eight-month period. Repeated measurements of cervical length
      using the computer-assisted method were compared with those carried out by two
      experienced sonographers. The median intraobserver variability for the 101 images
      using the computer-assisted method was significantly smaller than that of the
      manual method by either sonographer. In a pairwise comparison, the mean cervical
      length for the computer method matches with the mean manual cervical length.

PMID- 15484440
TI  - DBMap: a space-conscious data visualization and knowledge discovery framework for
      biomedical data warehouse.
AB  - Advances in digital imaging modalities as well as other diagnosis and therapeutic
      techniques have generated a massive amount of diverse data for clinical research.
      The purpose of this study is to investigate and implement a new intuitive and
      space-conscious visualization framework, called DBMap, to facilitate efficient
      multidimensional data visualization and knowledge discovery against the large
      scale data warehouses of integrated image and nonimage data. The DBMap framework
      is built upon the TreeMap concept. TreeMap is a space constrained graphical
      representation of large hierarchical data sets, mapped to a matrix of rectangles,
      whose size and color represent interested database fields. It allows the display
      of a large amount of numerical and categorical information in limited real estate
      of the computer screen with an intuitive user interface. DBMap has been
      implemented and integrated into a large brain research data warehouse to support
      neurologic and neuroradiologic research at the University of California, San
      Francisco Medical Center. For imaging specialists and clinical researchers, this
      novel DBMap framework facilitates another way to better explore and classify the
      hidden knowledge embedded in medical image data warehouses.

PMID- 15484441
TI  - A scalable mediator approach to process large biomedical 3-D images.
AB  - The Edinburgh Mouse Atlas is a spatial-temporal framework to store and analyze
      biological data including three-dimensional (3-D) images that relate to mouse
      embryo development. The purpose of the system is the analysis and querying of
      complex spatial patterns, in particular the patterns of gene activity during
      embryo development. The framework holds large 3-D gray level images and is
      implemented in part as an object-oriented database. In this paper, we propose a
      dynamic layered architecture, based on the mediator approach, for the design of a
      transparent and scalable distributed system which can process objects that can
      exceed 1 GB in size. The system's data are distributed and/or declustered across
      a number of image servers and are processed by specialized mediators.

PMID- 15484442
TI  - Robust model-based vasculature detection in noisy biomedical images.
AB  - This paper presents a set of algorithms for robust detection of vasculature in
      noisy retinal video images. Three methods are studied for effective handling of
      outliers. The first method is based on Huber's censored likelihood ratio test.
      The second is based on the use of a alpha-trimmed test statistic. The third is
      based on robust model selection algorithms. All of these algorithms rely on a
      mathematical model for the vasculature that accounts for the expected variations
      in intensity/texture profile, width, orientation, scale, and imaging noise. These
      unknown parameters are estimated implicitly within a robust detection and
      estimation framework. The proposed algorithms are also useful as nonlinear vessel
      enhancement filters. The proposed algorithms were evaluated over carefully
      constructed phantom images, where the ground truth is known a priori, as well as
      clinically recorded images for which the ground truth was manually compiled. A
      comparative evaluation of the proposed approaches is presented. Collectively,
      these methods outperformed prior approaches based on Chaudhuri et al. (1989)
      matched filtering, as well as the verification methods used by prior exploratory
      tracing algorithms, such as the work of Can et aL (1999). The Huber censored
      likelihood test yielded the best overall improvement, with a 145.7% improvement
      over the exploratory tracing algorithm, and a 43.7% improvement in detection
      rates over the matched filter.

PMID- 15484443
TI  - Reconstruction of 3-D head geometry from digitized point sets: an evaluation
      study.
AB  - In this paper, we evaluate different methods to estimate patient-specific scalp,
      skull, and brain surfaces from a set of digitized points from the target's scalp
      surface. The reconstruction problem is treated as a registration problem: An a
      priori surface model, consisting of the scalp, skull, and brain surfaces, is
      registered to the digitized surface points. The surface model is generated from
      segmented magnetic resonance (MR) volume images. We study both affine and free
      form deformation (FFD) registration, the use of average models, the averaging of
      individual registration results, a model selection procedure, and statistical
      deformation models. The registration algorithms are mainly previously published,
      and the objective of this paper is to evaluate these methods in this particular
      application with sparse data. The main interest of this paper is to generate
      geometric head models for biomedical applications, such as electroencephalography
      and magnetoencephalographic. However, the methods can also be applied to other
      anatomical regions and to other application areas. The methods were validated
      using 15 MR volume images, from which the scalp, skull, and brain were manually
      segmented. The best results were achieved by averaging the results of the FFD
      registrations of the database: the mean distance from the manually segmented
      target surface to a deformed a priori model surface for the studied anatomical
      objects was 1.68-2.08 mm, depending on the point set used. The results support
      the use of the evaluated methods for the reconstruction of geometric models in
      applications with sparse data.

PMID- 15484444
TI  - Comparison of two exploratory data analysis methods for fMRI: unsupervised
      clustering versus independent component analysis.
AB  - Exploratory data-driven methods such as unsupervised clustering and independent
      component analysis (ICA) are considered to be hypothesis-generating procedures,
      and are complementary to the hypothesis-led statistical inferential methods in
      functional magnetic resonance imaging (fMRI). In this paper, we present a
      comparison between unsupervised clustering and ICA in a systematic fMRI study.
      The comparative results were evaluated by 1) task-related activation maps, 2)
      associated time-courses, and 3) receiver operating characteristic analysis. For
      the fMRI data, a comparative quantitative evaluation between the three clustering
      techniques, self-organizing map, "neural gas" network, and fuzzy clustering based
      on deterministic annealing, and the three ICA methods, FastICA, Infomax and
      topographic ICA was performed. The ICA methods proved to extract features
      relatively well for a small number of independent components but are limited to
      the linear mixture assumption. The unsupervised Clustering outperforms ICA in
      terms of classification results but requires a longer processing time than the
      ICA methods.

PMID- 15484445
TI  - A digital video system for the automated measurement of repetitive joint motion.
AB  - Automated measurement and analysis of human motion during performance of
      workplace tasks are desirable for ergonomic studies. While numerous technologies
      exist for accurate measurement of biomechanical data, their use is often not
      feasible in the workplace environment. We present a digital-video based system
      suitable for measuring human motion of repetitive workplace tasks. Due to
      practical considerations, a single-camera solution is exploited by adding some
      control over the environment. We present an analysis of experiments demonstrating
      the accuracy of our system.

PMID- 15484446
TI  - Children's needs must be met now.

PMID- 15484447
TI  - Article explains the reality of nursing.

PMID- 15484448
TI  - MECA voting should have been delayed after floods.

PMID- 15484449
TI  - Supporting nurses affected by floods.

PMID- 15484450
TI  - Exposing double standards over prayers.

PMID- 15484451
TI  - Support needed for Nurses' Memorial Fund.

PMID- 15484453
TI  - Nursing intakes vary around the country.

PMID- 15484452
TI  - Identifying New Zealand nurses' uniforms.

PMID- 15484454
TI  - Oral history records nursing stories.

PMID- 15484455
TI  - Listening to children's views.

PMID- 15484456
TI  - ICN leader prepares for another demanding year.

PMID- 15484457
TI  - The role of overseas nurses in our health system.

PMID- 15484458
TI  - Cultural safety training should be compulsory.

PMID- 15484459
TI  - A journey to an unknown land.

PMID- 15484460
TI  - A different language and a different culture.

PMID- 15484461
TI  - The dangers of alcohol and pregnancy.

PMID- 15484462
TI  - Dental health is a key child health issue.

PMID- 15484463
TI  - Nursing on the foreshore.

PMID- 15484464
TI  - Children must be supported to grieve.

PMID- 15484465
TI  - Dealing with ethical challenges in practice.

PMID- 15484466
TI  - Research on nurse practitioner role underway.

PMID- 15484467
TI  - New bargaining criteria recommended.

PMID- 15484468
TI  - Targeting the aging and voting population.

PMID- 15484469
TI  - Government support for new graduate programmes vital.

PMID- 15484470
TI  - Funding shortages threaten graduate nurse programmes.

PMID- 15484471
TI  - Enrolled nurses can provide best care for acute patients.

PMID- 15484472
TI  - Treatment of enrolled nurses shocks mental health nurse.

PMID- 15484475
TI  - Clarifying Wintec's Tihei Mauri Ora focus.

PMID- 15484474
TI  - Honouring the psychopaedic nurse title.

PMID- 15484473
TI  - Fair Pay Campaign should unite all nurses.

PMID- 15484476
TI  - The unique challenges of outback nursing. Interview by Anne Manchester.

PMID- 15484477
TI  - Nursing abroad broadens horizons.

PMID- 15484478
TI  - Hand washing--rituals and regimes in practice.

PMID- 15484479
TI  - Assessment skills vital to sound nursing practice.

PMID- 15484480
TI  - Loss of NP title causes demoralisation.

PMID- 15484481
TI  - Fund will bring changes for nursing research.

PMID- 15484482
TI  - A cultural safety journey.

PMID- 15484483
TI  - Discovering the heart and soul of nursing.

PMID- 15484484
TI  - Celebrating 50 or more years of nursing.

PMID- 15484485
TI  - Reinforcing the patient safety message.

PMID- 15484486
TI  - Developing a model of professional maturity.

PMID- 15484499
TI  - Developing effective interdisciplinary teams.

PMID- 15484501
TI  - Challenging doctors' orders.

PMID- 15484500
TI  - How to say no to the bully at work.

PMID- 15484502
TI  - Witnessing resuscitation.

PMID- 15484503
TI  - MECA vote shows nurses' anger is rising.

PMID- 15484504
TI  - The world of nursing education funding.

PMID- 15484505
TI  - Men's health paper provided formative knowledge.

PMID- 15484506
TI  - Male nurse reflects back on his nursing career.

PMID- 15484507
TI  - Appreciating the diversity and complexity of humanity.

PMID- 15484508
TI  - Masters qualification fails to win financial recognition.

PMID- 15484509
TI  - Plea to Nursing Council to look after qualified nurses.

PMID- 15484511
TI  - NZNO called on to help build the anti-war movement.

PMID- 15484512
TI  - Employer's priorities criticised.

PMID- 15484513
TI  - New Zealanders all responsible for children who live on the streets.

PMID- 15484514
TI  - Hospital in the home innovation recognised.

PMID- 15484515
TI  - Celebrating International Nurses Day.

PMID- 15484516
TI  - Student debt is profoundly affecting nursing.

PMID- 15484517
TI  - Integrating research into daily practice.

PMID- 15484518
TI  - Taking education to the periphery.

PMID- 15484519
TI  - Coaching nurses to improved patient safety.

PMID- 15484520
TI  - Applying yourself.

PMID- 15484521
TI  - Understanding motor neurone disease.

PMID- 15484522
TI  - Coping with the diseases's progression.

PMID- 15484524
TI  - How students understand cultural safety.

PMID- 15484523
TI  - Introducing sociology to nursing students.

PMID- 15484525
TI  - Funding available for smear-taker training.

PMID- 15484526
TI  - Getting the most out of NZNO's library.

PMID- 15484527
TI  - Working upstream for those working downstream.

PMID- 15484528
TI  - Nurse shares 'essential ingredients' for independent practice.

PMID- 15484537
TI  - Encouraging healing through touch.

PMID- 15484538
TI  - Seeking an alternative way of providing health care.

PMID- 15484539
TI  - A young woman's triumph over violence.

PMID- 15484540
TI  - Plunket faces up to family violence.

PMID- 15484541
TI  - Using aromatherapy within nursing.

PMID- 15484543
TI  - Learning not to cross the boundaries.

PMID- 15484542
TI  - Helping children with enuresis and encopresis. Interview by Teresa O'Connor.

PMID- 15484544
TI  - Building better workplace relations.

PMID- 15484545
TI  - Looking at barriers to practice nurse development.

PMID- 15484546
TI  - Confronting prejudice and AIDS stigma.

PMID- 15484547
TI  - Providing a 'fast track' for nurse practitioners.

PMID- 15484548
TI  - 'Drawing a line in the sand' over nurse practitioners.

PMID- 15484549
TI  - Education trust criticises union campaign.

PMID- 15484550
TI  - Suggested cuts to education funding deplored.

PMID- 15484551
TI  - NZNO praised for taking anti-war stance.

PMID- 15484552
TI  - Free Internet cancer nursing course launched.

PMID- 15484553
TI  - Caregiver gatherings break new ground.

PMID- 15484554
TI  - Discovering the essence of caring.

PMID- 15484555
TI  - Giving hope and care to those living with HIV. Interview by Anne Manchester.

PMID- 15484556
TI  - Supporting people with HIV in the community. Interview by Anne Manchester.

PMID- 15484557
TI  - Challenging ignorance and prejudice. Interview by Anne Manchester.

PMID- 15484558
TI  - Fighting the HIV epidemic in the Pacific.

PMID- 15484559
TI  - NZNO makes the case for higher pay for nurses and midwives.

PMID- 15484560
TI  - Raising nurses' awareness of primary immune deficiency.

PMID- 15484561
TI  - Family health nursing in the Scottish Highlands.

PMID- 15484562
TI  - Collaboration is essential to improve health outcomes for children.

PMID- 15484563
TI  - Caring for those with HIV/AIDS.

PMID- 15484564
TI  - Good faith included in changes to holiday law.

PMID- 15484565
TI  - Sharing a passion for gerontology nursing.

PMID- 15484566
TI  - Direct communication among women must be encouraged.

PMID- 15484567
TI  - Nurses and pharmacists must work together for patients.

PMID- 15484568
TI  - Many health professionals involved in medications.

PMID- 15484569
TI  - Uncovering the art of gerontology nursing.

PMID- 15484570
TI  - Is caring for the elderly a valued role? Interview by Teresa O'Connor.

PMID- 15484571
TI  - Valuing older people and their carers. Interview by Teresa O'Connor.

PMID- 15484572
TI  - The demands of nursing a parent.

PMID- 15484573
TI  - Coping with the death of a staff member.

PMID- 15484574
TI  - A new voice for nursing students. Interview by Teresa O'Connor.

PMID- 15484575
TI  - Gerontology section paves the research pathway.

PMID- 15484576
TI  - NZNO's pay strategy on track.

PMID- 15484577
TI  - Seeing results. Building value into every visit to support patient loyalty and
      compliance.

PMID- 15484578
TI  - When getting soft is a good thing. A review of today's soft lens options.

PMID- 15484579
TI  - Jumping jacks. Kids, teens, and contact lenses.

PMID- 15484580
TI  - Getting off the treadmill. Tinted contact lenses.

PMID- 15484581
TI  - Contact lens cross training. Why contact lens wearers need spectacles. Why
      spectacle wearers need contact lenses.

PMID- 15484582
TI  - Tipping the scales in your favor. The importance of compliance in preventing
      problems.

PMID- 15484583
TI  - Let's not get physical. Handling contact lens Rx releases.

PMID- 15484584
TI  - Deep breath in and out. Handling contact lens emergencies.

PMID- 15484585
TI  - Immature cortical responses to auditory stimuli in specific language impairment:
      evidence from ERPs to rapid tone sequences.
AB  - Event-related potentials (ERPs) to tone pairs and single tones were measured for
      16 participants with specific language impairment (SLI) and 16 age-matched
      controls aged from 10 to 19 years The tone pairs were separated by an inter
      stimulus interval (ISI) of 20, 50 or 150 ms. The intraclass correlation (ICC) was
      computed for each participant between the ERP to a single tone and the ERP to the
      tone pair. A high ICC indicates that the brain response to a tone pair is similar
      to that for a single tone. ICCs were significantly higher at short than at long
      ISIs. At 50-ms ISI, ICCs were higher for younger than older participants. Age and
      ISI interacted with SLI status: ERPs of older participants with SLI differed from
      age-matched controls, and resembled ERPs of younger controls, consistent with a
      theory of immature auditory processing in SLI.

PMID- 15484586
TI  - Infants' reasoning about hidden objects: evidence for event-general and event
      specific expectations.
AB  - Research over the past 20 years has revealed that even very young infants possess
      expectations about physical events, and that these expectations undergo
      significant developments during the first year of life. In this article, I first
      review some of this research, focusing on infants' expectations about occlusion,
      containment, and covering events, all of which involve hidden objects. Next, I
      present an account of infants' physical reasoning that integrates these various
      findings, and describe new experiments that test predictions from this account.
      Finally, because all of the research I discuss uses the violation-of-expectation
      method, I address recent concerns about this method and summarize new findings
      that help alleviate these concerns.

PMID- 15484587
TI  - Is looking good enough or does it beggar belief?

PMID- 15484588
TI  - Who's for learning?

PMID- 15484589
TI  - Reasoning...what reasoning?

PMID- 15484590
TI  - Infants' attribution of a goal to a morphologically unfamiliar agent.
AB  - How do infants identify the psychological actors in their environments? Three
      groups of 12-month-old infants were tested for their willingness to encode a
      simple approach behavior as goal-directed as a function of whether it was
      performed by (1) a human hand, (2) a morphologically unfamiliar green object that
      interacted with a confederate and behaved intentionally, or (3) the same
      unfamiliar green object that behaved in a matched, but apparently random manner.
      Using a visual habituation technique, only infants in the first two conditions
      were found to encode the approach behavior as goal-directed Thus infants appear
      able to attribute goals to non-human, even unfamiliar agents. These results imply
      that by the end of the first year of life infants have a broad notion of what
      counts as an agent that cannot easily be reduced to humans, objects that are
      perceptually similar to humans, or objects that display self-propulsion.

PMID- 15484591
TI  - The Thatcher illusion and face processing in infancy.
AB  - Adults readily detect changes in face patterns brought about by the inversion of
      eyes and mouth when the faces are viewed upright but not when they are viewed
      upside down. Research suggests that this illusion (the Thatcher illusion) is
      caused by the interfering effects of face inversion on the processing of second
      order relational information (fine spatial information such as the distance
      between the eyes). In the current study, 6-month-olds discriminated
      'thatcherized' faces when they were viewed upright but not when they were viewed
      upside down. These results are consistent with the notion that 6-month-olds are
      sensitive to second-order relational information while processing faces.

PMID- 15484592
TI  - Imitation in neonatal chimpanzees (Pan troglodytes).
AB  - This paper provides evidence for imitative abilities in neonatal chimpanzees (Pan
      troglodytes), our closest relatives. Two chimpanzees were reared from birth by
      their biological mothers. At less than 7 days of age the chimpanzees could
      discriminate between, and imitate, human facial gestures (tongue protrusion and
      mouth opening). By the time they were 2 months old, however, the chimpanzees no
      longer imitated the gestures. They began to perform mouth opening frequently in
      response to any of the three facial gestures presented to them. These findings
      suggest that neonatal facial imitation is most likely an innate ability,
      developed through natural selection in humans and in chimpanzees. The
      relationship between the disappearance of neonatal imitation and the development
      of social communicative behavior is discussed from an evolutionary perspective.

PMID- 15484593
TI  - Switching between spatial stimulus-response mappings: a developmental study of
      cognitive flexibility.
AB  - Four different age groups (8-9-year-olds, 11-12-year-olds, 13-15-year-olds and
      young adults) performed a spatial rule-switch task in which the sorting rule had
      to be detected on the basis of feedback or on the basis of switch cues.
      Performance errors were examined on the basis of a recently introduced method of
      error scoring for the Wisconsin Card Sorting Task (WCST; Barcelo & Knight, 2002).
      This method allowed us to differentiate between errors due to failure-to-maintain
      set (distraction errors) and errors due to failure-to-switch-set (perseverative
      errors). The anticipated age differences in performance errors were most
      pronounced for perseverative errors between 8-9 years and 11-12 years, but for
      distraction errors adult levels were not reached until 13-15 years. These
      findings were interpreted to support the notion that set switching and set
      maintenance follow distinct developmental trajectories.

PMID- 15484594
TI  - A visit from the Candy Witch: factors influencing young children's belief in a
      novel fantastical being.
AB  - Factors hypothesized to affect beliefs in fantastical beings were examined by
      introducing children to a novel fantastical entity, the Candy Witch. Results
      revealed that among older preschoolers, children who were visited by the Candy
      Witch exhibited stronger beliefs in the Candy Witch than did those who were not.
      Among children who were visited, older children had stronger beliefs than did
      younger children. Among children who were not visited, those with a high Fantasy
      Orientation believed more strongly than did those with a low Fantasy Orientation.
      Belief remained high one year later. At both time points, the number of other
      fantastical beings in which a child believed was significantly related to belief
      in the Candy Witch.

PMID- 15484595
TI  - Effects of repetition and configural changes on the development of face
      recognition processes.
AB  - We investigated the effect of repetition on recognition of upright, inverted and
      contrast-reversed target faces in children from 8 to 15 years when engaged in a
      learning phase/test phase paradigm with target and distractor faces. Early (P1,
      N170) and late ERP components were analysed Children across age groups performed
      equally well, and were better at recognizing upright faces. However, teenagers
      and adults were equally accurate for all three face types. The neurophysiological
      responses to upright, inverted and negative faces matured until adulthood and
      showed different effects at different ages. P1 and N170 components were affected
      by face type at all ages, suggesting early configural disruption on encoding
      processes regardless of age. Frontal ERPs reflected the difficulty of processing
      these stimuli. Distinct repetition effects were seen at frontal, temporal frontal
      and parietal sites, suggesting differential involvement of these brain regions
      underlying working memory and recognition processes. Thus, a learning phase was
      sufficient (a) for 8-year-olds to perform as accurately as 15-year-olds and (b)
      to eliminate face type effects in teenagers and adults, but not in younger
      children.

PMID- 15484596
TI  - 'Unwilling' versus 'unable': chimpanzees' understanding of human intentional
      action.
AB  - Understanding the intentional actions of others is a fundamental part of human
      social cognition and behavior. An important question is therefore whether other
      animal species, especially our nearest relatives the chimpanzees, also understand
      the intentional actions of others. Here we show that chimpanzees spontaneously
      (without training) behave differently depending on whether a human is unwilling
      or unable to give them food Chimpanzees produced more behaviors and left the
      testing station earlier with an unwilling compared to an unable (but willing)
      experimenter These data together with other recent studies on chimpanzees'
      knowledge about others' visual perception show that chimpanzees know more about
      the intentional actions and perceptions of others than previously demonstrated

PMID- 15484597
TI  - Subtitled videos and mismatch negativity (MMN) investigations of spoken word
      processing.
AB  - The purpose of this study was to determine whether the presence of subtitles on a
      distracting, silent video affects the automatic mismatch negativity (MMN)
      response to simple tones, consonant-vowel (CV) nonwords, or CV words. Two
      experiments were conducted in this study, each including ten healthy young adult
      subjects. Experiment 1 investigated the effects of subtitles on the MMN response
      to simple tones (differing in frequency, duration, and intensity) and speech
      stimuli (CV nonwords and CV words with a /d/-/g/ contrast). Experiment 2
      investigated the effects of subtitles on the MMN response to a variety of CV
      nonword and word contrasts that incorporated both small (e.g., /d/ vs. /g/)
      and/or large (e.g., /e:/ vs. /el/) acoustic deviances. The results indicated that
      the presence or absence of subtitles on the distracting silent video had no
      effect on the amplitude of the MMN or P3a responses to simple tones, CV nonwords,
      or CV words. In addition, the results also indicated that movement artifacts may
      be statistically reduced by the presence of subtitles on a distracting silent
      video. The implications of these results are that more "engaging" (i.e.,
      subtitled) silent videos can be used as a distraction task for investigations
      into MMN responses to speech and nonspeech stimuli in young adult subjects,
      without affecting the amplitude of the responses.

PMID- 15484599
TI  - Limiting high-frequency hearing aid gain in listeners with and without suspected
      cochlear dead regions.
AB  - The purpose of this study was to compare threshold-matched ears with and without
      suspected cochlear dead regions in terms of the speech perception benefit from
      high-frequency amplification. The Threshold Equalizing Noise Test (TEN) was used
      to assess the presence of dead regions. Speech perception was measured while
      participants were wearing a hearing aid fit to approximate DSL[i/o] targets.
      Consonant identification of nonsense vowel-consonant-vowel combinations was
      measured in quiet using a forced-choice procedure. Phoneme recognition was
      measured at signal-to-noise ratios ranging from 0 to +15 dB using the Computer
      Assisted Speech Perception Assessment test (CASPA). Recognition scores were
      obtained for unfiltered stimuli and stimuli that were low-pass filtered at the
      estimated boundary of the suspected dead regions, 1/2 octave above and 1 octave
      above the boundary. Filter settings for the ears without suspected dead regions
      were the same as settings of the threshold-matched counterpart. In quiet and in
      low levels of noise, speech perception scores were significantly higher for the
      wide-band (unfiltered) condition than for the filtered conditions, and
      performance was similar for the ears with and without suspected dead regions. In
      high levels of noise, mean scores were highest in the wide-band condition for the
      ears without suspected dead regions, but performance reached an asymptote for the
      ears with suspected dead regions. These results suggest that patients with
      cochlear dead regions may experience speech perception benefit from wide-band
      high-frequency gain in quiet and low levels of noise, but not in high levels of
      noise.

PMID- 15484598
TI  - Revisiting loudness measures in children using a computer method of cross
      modality matching (CMM).
AB  - The test efficiency and reliability of loudness assessment using a computer
      controlled method of cross-modality matching (CMM) between line length and
      loudness was investigated in children 4 to 12 years with normal hearing or mild
      to severe degrees of sensorineural hearing loss. Adult listeners with normal
      hearing served as a comparison group. Computer-generated visual and acoustic
      stimuli were used to derive individual loudness data. Children and adults with
      normal hearing presented with similar loudness functions, while children with
      sensorineural hearing loss had steeper functions than their normal-hearing
      counterparts. Retest data supported reliability of the CMM method with children
      within the current study and between previous studies performed with a similar,
      but manual, method. The computer CMM approach proved more time efficient than the
      manual one, halving the test time. The CMM loudness task in a computerized
      version may have potential in a research or clinical setting, in particular for
      individualizing hearing aid fittings with children.

PMID- 15484600
TI  - Speech intelligibility of young school-aged children in the presence of real-life
      classroom noise.
AB  - We examined the ability of 40 young children (aged five to eight) to understand
      speech (monosyllables, spondees, trochees, and trisyllables) when listening in a
      background of real-life classroom noise. All children had some difficulty
      understanding speech when the noise was at levels found in many classrooms (i.e.,
      65 dBA). However, at an intermediate (-6 dB SNR) level, kindergarten and grade 1
      children had much more difficulty than did older children. All children performed
      well in quiet, with results being comparable to or slightly better than those
      reported in previous studies, suggesting that the task was age appropriate and
      well understood. These results suggest that the youngest children in the school
      system, whose classrooms also tend to be among the noisiest, are the most
      susceptible to the effects of noise.

PMID- 15484601
TI  - ERP evidence of a dichotic left-ear deficit in some dyslexic children.
AB  - Children with and without behavioral dichotic left-ear deficits participated in
      an event-related potential study with quasidichotic presentations of familiar
      fairy tale segments. Electrical activity was recorded from the scalp while the
      children listened for semantically and/or syntactically anomalous words from
      either the right side or the left side while competing segments of the fairy tale
      were simultaneously presented from the opposite side. Latencies and amplitudes
      were averaged for each target condition within the group with dichotic left-ear
      deficits (LED) and the group with normal dichotic listening performance (WNL).
      Individual global field power waveforms and topographic brain maps were generated
      for the average response in each of the two listening conditions, target right
      and target left. Cross-correlations were performed on the grand averaged global
      field power waveforms to measure the degree of synchrony between target right and
      target left responses in both groups. Integration functions were performed to
      compare the accumulated sum of voltages during target (right and left) and
      control (right and left) conditions. WNL children produced typical ERP responses
      to the target words in both target right and target left conditions. Responses
      from LED children were at delayed latencies in the target left condition and were
      at reduced amplitudes in both target conditions. Topographic brain maps revealed
      more lateralized scalp distributions and greater activation of frontal regions in
      LED children in the target left condition. Cross-correlational and integration
      function results demonstrated interaural asymmetries in responses from the LED
      children. Overall results suggest that slowed neural conduction times, poor
      interhemispheric transfer of neural activity, and a failure to suppress competing
      information arriving at the right ear may be involved in poor left-sided
      processing in children with behavioral left-ear dichotic deficits.

PMID- 15484602
TI  - Setting priorities for research.
AB  - Setting priorities for research should be conducted in order to make the most
      efficient use of scarce resources. Yet the uptake in practice of such methods by
      researchers and commissioners of research alike has been slow, in part because
      the methodologies available to do so have not been widely disseminated. This
      paper argues that an appropriate priority-setting methodology should meet the
      objectives of the health system, that is to provide the most health benefits to
      the population that it serves within the budget constraint and while respecting
      equity considerations. A condition for these criteria to be met is to construct
      and operationalise an appropriate definition of the value of research. Five
      different ways that have been used in practice to value research and set
      priorities were reviewed. Shortcomings in the ways research is valued make it
      unlikely that the application of subjective methods, burden of disease methods,
      and clinical variations and payback methods meet the objectives of the health
      system. Using the fifth method, value of information, priority-setting can meet
      the objectives of the health system because it expresses the value of research
      using the same overall cost-effectiveness framework that is employed for
      decisions on service provision. However, this method still requires further work
      to evaluate how research outcomes can then be communicated to clinical
      practitioners and how practitioners can be encouraged to implement them.

PMID- 15484603
TI  - Association of hospital ownership with patient transfers to outpatient care under
      a prospective payment system in Taiwan.
AB  - Case payment, a prospective payment system akin to diagnosis-related groups
      (DRGs) has in-built incentives for hospitals to transfer inpatients to their own
      ambulatory care units following early discharge. This study used nation-wide
      inpatient claims data on a total of 100,730 patients treated in 2000 in (Taiwan):
      cesarean section (59,364 cases), femoral/inguinal hernia operation (18,675
      cases), and hemorrhoidectomy (22,691 cases), all reimbursed by case payment, to
      explore the relationship between hospital ownership and patient transfers to
      outpatient treatment. For all three diagnoses, for-profit (FP) hospitals not only
      had lower lengths of stay (LOS) compared to public hospitals, but also showed
      very high odds of patient transfer to their own outpatient units, after
      controlling for institutional variables, (hospital level, teaching status, and
      geographic location), hospital competitive environment (the Herfindal-Hirschman
      index), and patient variables (gender, age, length of stay, and number of
      secondary diagnoses, a proxy for severity of illness). Similar, though slightly
      lower odds were observed with not-for-profit (NFP) hospitals relative to public
      hospitals. The findings support the property rights theory, suggesting that in
      Taiwan, institutional profit maximization motives may be driving patient
      transfers under the case payment diagnoses, rather than medical care needs. In
      NFP hospitals, their physician compensation mechanism, driven largely by care
      volumes provided by each physician, appears to be driving the disproportionately
      greater likelihood of patient transfer to outpatient care.

PMID- 15484604
TI  - Contracting for health services in a public health system: the New Zealand
      experience.
AB  - This paper reports on the process and outcomes of contracting for health services
      in New Zealand between 1993 and 2000 when a purchaser-provider split was in
      place. Key factors that shaped the contracting environment were the legal
      framework, funding constraints, and the cultural and professional norms of
      contracting personnel. A lack of good information-especially on costs, volumes
      and quality-increased the costs of contracting and made monitoring and
      accountability difficult. Over time, however, the contracting process became
      simpler and less costly. Overall, the introduction of contracting generally
      improved the focus of providers on costs and volumes; led to greater clarity
      through specification of services; encouraged providers to focus on methods to
      improve quality; and enabled new styles of service provision from providers that
      had not traditionally received public funds for health services. Good
      relationships between purchasers and providers were seen as the key to successful
      contracting.

PMID- 15484605
TI  - Networks for integrated care provision: an economic approach based on opportunism
      and trust.
AB  - In this paper, we provide the economic rationale for an important issue in the
      health care sector, namely the network formation, e.g., in The Netherlands. The
      presence of such cooperation structures is hard to explain using the basic
      concept of the economic organization (EO) theory, i.e., the dichotomy of
      hierarchy versus market. However, acknowledging the aspect of trust renders the
      clan concept to be a powerful tool in understanding the viability of intra- and
      inter-organizational cooperation in the health sector. The main reason for this
      is the manner in which the professionals involved perform, as well as the
      importance of the tacit knowledge of the actors employed in the various health
      institutions. First, we address the conversion from supply towards demand
      orientation and the resulting pressure on multi-professional cooperation between
      health care providers. Then, relevant EO concepts will be reviewed, while
      introducing theory on knowledge, learning, and trust. Moreover, we offer
      conclusions for the health care sector on a concept-by-concept basis. Finally, we
      propose the notion of interclan, a clan-inspired notion for inter-organizational
      cooperation, and analyse the observed network formation.

PMID- 15484606
TI  - The feasibility of community-based health insurance in Burkina Faso.
AB  - To ensure the acceptability of community-based insurance (CBI) by the community
      and its sustainability, a feasibility study of CBI was conducted in Burkina Faso,
      including preference for benefit package of CBI, costing of health services,
      costing of the benefit package and willingness-to-pay (WTP) for the package.
      Qualitative methods were used to collect information about preferences for the
      benefit package. Cost per unit health services, health demand obtained from
      household survey and physician-judged health needs were used to estimate the cost
      of the benefit package. The bidding game method was used to elicit household
      head's WTP for the package. We found that there were strong preferences for
      inclusion of high-cost healthservices such as operation, essential drugs and
      consultation fees in the benefit package. It is estimated that the cost of the
      package per capita was 1673 CFA (demand-based) and 9630 CFA (need-based),
      including 58% government subsidies (euro 1 = 655 CFA). The average household head
      with eight household members agreed to pay from 7500 (median) to 9769 CFA (mean)
      to join the CBI for his/her household. The WTP results were influenced by
      household characteristics, such as location, household size and age composition.
      Under certain assumptions (household as the enrolment unit, median household
      head's WTP as premium for the average household, 50% enrolment rate), it would be
      feasible to run CBI in Nouna, Burkina Faso if enrolees' health demand did not
      increase by more than 28% or if the underwriting of the initial losses was
      covered by extra funds.

PMID- 15484607
TI  - Technical efficiency in the use of health care resources: a comparison of OECD
      countries.
AB  - Our paper analyzes technical efficiency in the production of aggregate health
      outcomes of reduced infant mortality and increased life expectancy, using
      Organization for Economic Cooperation and Development (OECD) health data.
      Application of data envelopment analysis (DEA) reveals that some countries
      achieve relative efficiency advantages, including those with good health outcomes
      (Japan, Sweden, Norway, and Canada) and those with modest health outcomes (Mexico
      and Turkey). We conclude the USA may learn from countries more economical in
      their allocation of healthcare resources that more is not necessarily better.
      Specifically, we find that the USA can substantially reduce inputs while
      maintaining the current level of life expectancy.

PMID- 15484608
TI  - The relative importance of leadership and payment system. Effects on quality of
      care and work environment.
AB  - The key question addressed in this study is whether the introduction of stronger
      financial incentives in health care give rise to such a restrictive context that
      leadership has only a minor influence? Or is good leadership, on the contrary,
      important to the achievement of both financial and other goals, regardless of
      contextual factors? Physicians in one Swedish County Council with performance
      based reimbursement and in 10 councils without such a system were studied in a
      cross-sectional questionnaire study. The result of this study indicates that
      although contextual factors were of substantial importance there is scope for
      leaders to act, and their actions make a considerable difference, both for the
      experience of the work process and for the outcome in terms of work environment
      and quality of care. A good leadership may be able to shield the health care
      organisation from unwanted side effects of increased financial pressure.

PMID- 15484609
TI  - Shifting the burden of health care finance: a case study of public-private
      partnership in Singapore.
AB  - Since becoming independent in 1965, Singapore has attained high standards in
      health care provision while successfully transferring a substantial portion of
      the health care burden to the private sector. The government's share of total
      health care expenditure contracted from 50% in 1965 to 25% in 2000. At first
      glance, the efficiency-driven health care financing reforms which emphasize
      individual over state responsibility appear to have been implemented at the
      expense of equity. On closer examination, however, Singaporeans themselves seem
      unconcerned about any perceived inequity of the system. Indeed, they appear
      content to pay part of their medical expenses, plus additional monies if they
      demand a higher level of services. In fact, access to needed care for the poor is
      explicitly guaranteed. Mechanisms also exist to protect against financial
      impoverishment resulting from catastrophic illness. Singapore's experience
      provides an interesting case study in public-private partnership, illustrating
      how a hard-headed approach to health policy can achieve national health goals
      while balancing efficiency and equity concerns.

PMID- 15484610
TI  - Describing Chinese hospital activity with diagnosis related groups (DRGs). A case
      study in Chengdu.
AB  - OBJECTIVE: To examine the applicability of an Australian casemix classification
      system to the description of Chinese hospital activity. DESIGN: A total of
      161,478 inpatient episodes from three Chengdu hospitals with demographic,
      diagnosis, procedure and billing data for the year 1998/1999, 1999/2000 and
      2000/2001 were grouped using the Australian refined-diagnosis related groups (AR
      DRGs) (version 4.0) grouper. MAIN OUTCOME MEASURES: Reduction in variance (R2)
      and coefficient of variation (CV). RESULTS: Untrimmed reduction in variance (R2)
      was 0.12 and 0.17 for length of stay (LOS) and cost respectively. After trimming,
      R2 values were 0.45 and 0.59 for length of stay and cost respectively.
      CONCLUSIONS: The Australian refined DRGs provide a good basis for developing a
      Chinese grouper.

PMID- 15484611
TI  - The healthcare experiences of Arab Israeli women in a reformed healthcare system.
AB  - Arab Israeli women are subject to unique social stresses deriving from their
      status as part of an ethno-political minority and from their position as women in
      a patriarchal community. Collectively, their health profiles rate poorly in
      comparison to Jewish Israeli women or to women in the vast majority of developed
      countries. OBJECTIVES: To examine the experiences of Arab Israeli women in the
      contemporary Israeli healthcare system, following implementation of the National
      Health Insurance Law (NHIL). METHODS: The study combined quantitative and
      qualitative research methodologies. A telephone survey utilizing a structured
      questionnaire was conducted during August-September 1998 among a random national
      sample of 849 women, with a response rate of 83%. Between the months of January
      and July of 2000, qualitative data was attained via participant-observation, long
      and short semi-structured interviews, and focus groups in one large Muslim Arab
      Israeli village. FINDINGS: Arab Israeli women in the national survey reported
      poorer self-assessed health, lower rates of care by a woman primary care
      physician, lower satisfaction ratings for primary care physicians and more
      frequently foregoing medical care than did native or immigrant Jewish Israeli
      women. Three major factors contributing to Arab Israeli women's healthcare
      experiences were elucidated by the qualitative study: (1) the threat of physical
      and social exposure (2) difficulties in communicating with male physicians and
      (3) the stifling effect of family politics and surveillance on healthcare.
      DISCUSSION: We discuss our findings in relation to structural changes associated
      with the recent reform of the Israeli health care system. We conclude by
      suggesting policy measures for better adapting primary care services to the needs
      of Arab Israeli women, and note the relevance to other systems that aim to
      provide service to cultural and ethno-political minorities, in which healthcare
      delivery is shaped by unique local circumstances.

PMID- 15484612
TI  - Pakistan's maternal and child health policy: analysis, lessons and the way
      forward.
AB  - An estimated 400,000 infant and 16,500 maternal deaths occur annually in
      Pakistan. These translate into an infant mortality rate and maternal mortality
      ratio that should be unacceptable to any state. Disease states including
      communicable diseases and reproductive health (RH) problems, which are largely
      preventable account for over 50% of the disease burden. The analysis of
      Pakistan's maternal and child health (MCH) and family planning (FP) policy covers
      the period 1990-2002, and focuses on macroeconomic influences, priority programs
      and gaps, adequacy of resources, equity and organizational aspects, and the
      process of policy formulation. The overall MCH/FP policy is well directed. MCH/FP
      has been a priority in all policies; resource allocation, although unacceptably
      low, has substantially increased during the last decade; and there is a
      progressive shift from MCH to the reproductive health (RH) agenda. Areas in need
      of improvement include greater use of evidence as a basis for policy; increased
      priority to nutrition programs, measures to reduce neonatal and perinatal
      mortality, provision of emergency obstetric care, availability of skilled birth
      attendants, and a clear policy on integrated management of childhood illnesses.
      Enhanced planning capacity, development of a balanced human resource, improved
      governance to reduce staff absenteeism and frequent transfers, and a greater role
      of the private sector in the provision of services are some organizational
      aspects that need the governments' consideration. There are several lessons to be
      learnt: (i) Ministries of Health need sustained stewardship and well-documented
      evidence to protect cuts in resource allocation; (ii) frequent policy
      announcement sends inappropriate signals to managers and weakens on-going
      implementation; (iii) MCH/FP policies unless informed by evidence and
      participation of interest groups are unlikely to address gaps in programs; (iv)
      distributional and equity objectives of MCH/FP be addressed while setting overall
      national goals; (v) institutional capacity is a vital ingredient in translating
      MCH/FP policies into effective services. The suggested strategic directions
      emphasize, among others, the need for a comprehensive MCH/FP framework;
      strengthened stewardship in ministry of health, cost-effective strategies to
      address the gaps identified and doubling of the public sector resource allocation
      to MCH/FP over the next 5 years. The ability to ensure delivery of quality health
      services remains the biggest challenge in the Pakistani health sector. Unless
      sound policies are backed by well-functioning programs they are likely to become
      a victim of poor implementation.

PMID- 15484613
TI  - Contemporary trends.

PMID- 15484614
TI  - Professional regulation: determinants and strategies.
AB  - This paper discusses the nature of nursing's social contract, in particular the
      way in which nursing practice is or should be regulated in order to contribute to
      quality health care. Given that professional autonomy is linked to regulation,
      registration, education requirements and institutional policy and procedure,
      setting the limitations of the current model of regulation of entry to practice
      and disciplinary action for default, are questioned. The concept of personal
      responsibility for practice is introduced along with possible strategies for the
      ongoing validation of professional practice.

PMID- 15484615
TI  - Living with difference: caring for a premature baby at home.
AB  - This grounded theory study explores the experience of caring for a premature baby
      following discharge from hospital. The idea for the study arose from our nursing
      practice with new parents. Seven participants from one region contributed to the
      development of a substantive theory, which we named "Living with Difference:
      Caring for a premature baby at home". The participants were convinced that their
      experience was different from that of mothers of full-term babies. The women
      articulated the areas of difference as being: needing and receiving support;
      developing confidence; feeling guilty, and experiencing smallness. The results
      from this study will contribute to a body of knowledge which will inform future
      family and child health practice.

PMID- 15484616
TI  - Computerised clinical pathway management systems and the implications.
AB  - This is the second paper of the two-part series. Part 1 of the series
      (Reconceptualising Clinical Pathway System Design) reported defects existed in
      the paper clinical pathways and proposed a set of design premises to guide the
      development of a computerised clinical pathway management system (CCPMS). This
      paper provides an overview of a robust CCPMS that was designed to accurately map
      patients' changing clinical states and support dynamic modification of the
      clinical pathway structure and associated interventions. This electronic system
      provides clinicians with real time outcome feedback on care delivered and
      generates alerts on out of range assessment results, deteriorating trends and
      potential problems such as drug interactions. It has been rated by clinicians who
      participated in an evaluative study as a highly useful information management and
      decision support tool. However, the introduction of a power tool like the
      clinical pathway management system has raised very important issues such as the
      need for work practice redesign, education of clinicians and more research to
      maximise the benefits of the tool and achieve better process quality improvement.
      It also generates serious concerns about legal liabilities and the potential
      threat of the cost cutting strategies taken by senior management in search of
      paybacks after their implementation. These issues and their implications are also
      explored in this paper.

PMID- 15484617
TI  - Work related trauma.

PMID- 15484618
TI  - The Greenwood et al article.

PMID- 15484619
TI  - An outline of consumer participation in health.
AB  - Awareness about the importance of consumers' participating in decision making in
      health is being increasingly advocated as a way of improving the safety and
      quality of health care. This article briefly describes some of the key
      international and national health directions and research that support a more
      active role for consumers in decision making in health. In addition, it proposes
      four key dimensions of consumer participation as a framework to describe the
      scope for consumers to participate in decision-making in individual care
      processes, health services and the broader health system. Finally, a new
      Commonwealth Government funded initiative, the National Resource Centre for
      Consumer Participation in Health, is described which aims to increase the access
      of service providers and consumer organisations to information about the various
      methods and models of consumer feedback and participation and provide support to
      enhance their application of the methods and models to practice.

PMID- 15484620
TI  - Hairdressing and nursing: presentation of self and professional formation in
      colonial Australia.
AB  - When Lucy Osburn led her team of Nightingale sisters to the Sydney Infirmary in
      1868 she knew that a challenge awaited her. Her goal was to transform the
      colony's only public hospital into a respectable, ordered environment where,
      according to the Sanitarian view of the universe espoused by Miss Nightingale,
      the patient would find the resources to heal himself (sic). The prime difficulty
      was not the filth and disorder of the institution, it was the calibre of the
      nurses. This paper offers a case study into the issues of presentation of self,
      institutional shaping and the professional formation of nurses in the late
      nineteenth and early twentieth century. The aesthetics of bodily grooming and the
      class and ethnic issues embedded in the professionalisation of nursing will be
      discussed. The story of nursing provides an exemplar of the disaggregation of a
      domain of female expertise. The translation of this expertise to a mass
      occupation embodied significant difficulties. Not the least of these difficulties
      was the problem nursing leaders encountered when attempting to instil certain
      personal attributes and vocational values in non pious common women. It will be
      argued here that it was the inculcation of a specific set of attributes that
      created the nurse. It is this persona of the nurse, and the challenge that it
      presented for colonial nurses in the late nineteenth and early twentieth
      centuries, that this paper explores.

PMID- 15484621
TI  - Nursing and health care in Iceland.

PMID- 15484623
TI  - Nausea and vomiting in the patient with advanced cancer: an overview of
      pharmacological and non-pharmacological management.

PMID- 15484622
TI  - The impact of work-related trauma on the well-being of perioperative nurses.
AB  - Perioperative nurses are confronted daily with the reality of trauma, of
      experiencing abuse and conflict in the workplace, dealing with practice issues
      such as gruesome motor vehicle accidents, as well as the heartbreaking tragedy of
      death (Michael 1999, Michael & Jenkins 2000). This study explored the reported
      impact of traumatic events upon the well-being of perioperative nurses, using
      both qualitative and quantitative methods of inquiry. Of the 233 respondents in
      this study, 161 (69%) reported being exposed to traumatic events. The types of
      described reactions following trauma were predominantly negative and included
      negative feelings, negative team member relationship issues, negative behaviour
      from others, physical concerns and negative working conditions. Intrusion and
      avoidance behaviour was reported to a significant degree. Performance distress,
      somatic distress, general feelings of distress and self-related health were
      significantly poorer in perioperative nurses who had experienced trauma, than
      their colleagues without such experiences. Conversely, some respondents were able
      to construe positive outcomes from trauma and grow from the experience. Positive
      outcomes included gains from the experience, team building, positive feelings and
      action taken. The current study contributes to understanding of the role of
      environmental factors, associated work-related trauma and recovery following such
      events. The outcomes have implications for effective trauma stress management
      interventions and continuing education of nurses.

PMID- 15484624
TI  - Regulating ethics.

PMID- 15484625
TI  - Mission impossible?
AB  - In 1999 the authors submitted to the local Health Research Ethics Committee
      (HREC) for approval a research proposal to investigate Institutional Ethics
      Committee (IEC) policies and practices in Greater Sydney, Australia. The
      submission to the HREC followed previous successful submissions to the Scientific
      Advisory Committee, which is a sub-committee of the HREC and the IEC of the
      University of Western Sydney, Nepean. The local HREC refused to approve the
      proposal. In this paper we describe the study's background, its aims, expected
      outcomes and its design. We also describe the scientific and ethical review
      process to which the research proposal was subjected. Finally, we speculate upon
      the reasons the proposal's progress has been, in our view, inappropriately
      impeded. These illustrate with pressing irony precisely those issues the proposed
      research sought to explore and address.

PMID- 15484626
TI  - On the fast track.
AB  - It has been suggested in nursing literature that a bachelor's degree should be
      the pre-requisite to professional nursing education and registration. The
      perceived advantages of graduates entering the nursing profession led faculty in
      the School of Nursing La Trobe University to introduce in 1997 an innovative two
      year Bachelor of Nursing (BN) program, believed to be the first in Australia, for
      graduates of other disciplines. A problem-based learning (PBL) approach was
      selected to facilitate the teaching learning process. Data to evaluate the
      progress of the accelerated students were collected by examining their previous
      degree background, conducting a focus group discussion mid year and comparing the
      students' academic results with those completing the traditional three-year
      course. Findings indicate that students in the accelerated course were highly
      motivated but experienced significant stress. In part the stress emanated from
      the need to identify their own learning needs. However, despite their concerns
      most accelerated students scored at least as well both clinically and
      academically as traditional students. Moreover, in six of the seven final year
      subjects each group studied the accelerated students performed better.

PMID- 15484627
TI  - Work-related trauma: the experiences of perioperative nurses.
AB  - Traumatic experiences in the workplace are an integral part of the role of the
      perioperative nurse. The atypical nature and characteristics of these experiences
      is such that perioperative nurses may suddenly encounter reactions and feelings
      that are very different and more intense than anything they will have encountered
      previously. Furthermore, these events may increase the risk of them experiencing
      subsequent trauma stress reactions and place them at risk of profound distress
      and significantly impaired functioning. A survey of 233 nurses working in rural
      and metropolitan operating theatres assessed the range and types of traumatic
      work experiences. Results showed that exposure to traumatic events was reported
      by 161 (69%) of all respondents and a wide range of traumatic experiences were
      reported to have affected their well-being. The findings have implications for
      the formulation of trauma management strategies, both at individual and
      organisational levels and suggest new directions for education and research in
      promoting a recovery environment in which perioperative nurses can work.

PMID- 15484628
TI  - Aspects of caring in Australian nursing.
AB  - In January 1998 an article appeared in Collegian that examined the contested
      workplace between degreed and non-degreed nurses and reported that many non
      degree nurses think that study at tertiary level symbolises that caring has gone
      out of nursing. Around the same time in Western Australia a political argument
      was put forward that voiced similar views about tertiary-educated nurses. In
      order to illustrate that caring is central to nursing practice, this article
      presents some findings derived from a larger phenomenological study. Despite the
      fact that descriptions of caring were not sought in this study, the data included
      many descriptions of health-focused care that were undeniably caring in nature.
      Caring showed in the descriptions of health-focused care as a preoccupation, an
      almost total involvement for the nurses in the task at hand, even if only for a
      limited period of time. It involved a considerable investment of self on the part
      of the nurse and a lack of comfort with self because of feelings of
      responsibility for another. Caring involved the act of taking another's wellbeing
      temporarily into the nurse's domain and the giving of devoted attention to
      another. It required the nurse to engage in rapport building so that she or he
      might support the other with consideration and respect and be concerned about the
      dignity of the other. This article explores the literature on caring in relation
      to these data in an attempt to generate ongoing discussion and further research
      about the nature of caring in Australian nursing so that doubts about the
      existence of caring in nursing may be put to rest.

PMID- 15484629
TI  - Reconceptualising clinical pathway system design.
AB  - Increased patient throughput and patient acuity resulting from the introduction
      of prospective funding mechanisms, such as Case Mix (based on the Diagnosis
      Related Groups) for in-patient acute care, raised serious concerns about
      compromising quality of care delivered to patients. The paper clinical pathway
      has been introduced as a tool to streamline documentation, implement standardised
      clinical management protocols and improve quality of care provided to patients.
      However, the checklist format and its lack of connection to clinical data
      reflecting changes in patient status have imposed severe limitations on the
      ability of clinical pathway to be used as an effective information management and
      decision support tool. This is the first of two papers reporting on a research
      effort that was undertaken to identify, validate and address the limitations of
      paper clinical pathways. A set of functional specifications and a functional
      model were developed following the initial exploratory study. The work led to a
      set of reconceptualised system (CCPMS) design guidelines for the development of a
      robust computerised clinical pathway management system that could provide dynamic
      information management and decision support to clinicians in response to changing
      patient clinical status. The second paper will report on the features and
      benefits demonstrated by the CCPMS prototype. Implications to nursing brought
      about by the introduction of such a tool will also be explored.

PMID- 15484631
TI  - Clinical information systems.

PMID- 15484630
TI  - Response and reflections on Bruni's 1988 critique of Leininger's theory.

PMID- 15484632
TI  - Nausea and vomiting in the patient with advanced cancer: an overview of
      prevalence, causes and assessment.

PMID- 15484633
TI  - Management of the child with neurofibromatosis Type I, von Recklinghausen
      Disease.

PMID- 15484634
TI  - Analysis of the human periodontal ligament fibroblast response to the cytolethal
      distending toxin produced by actinobacillus actinomycetemcomitans.
AB  - A small number of diverse bacterial pathogens have been found to produce
      cytolethal distending toxin (CDT). Much evidence has been obtained to show that
      CDTs cause a variety of eukaryotic cells to become irreversibly blocked in the G2
      phase of the cell cycle. Cells which are sensitive to CDT, such as Chinese
      hamster ovary (CHO) cells, die within a few days after exposure to the toxin.
      Recent research has shown that CDT is a potential virulence factor for
      Actinobacillus actinomycetemcomitans, a bacterial species associated with
      juvenile periodontitis (JP). This research investigates the effects A.
      actinomycetemcomitans CDT has on human periodontal ligament fibroblasts (HPDLFs).
      After HPDLFs were exposed to physiologic levels of CDT, cell viability was
      assessed utilizing an assay that measured the conversion of a tetrazolium
      compound into a soluble formazan product, which could be read on a
      spectrophotometer. Cell viability was also measured after exposure to CDT through
      trypan blue staining and the use of a hemocytometer. CHO cells were utilized as a
      parallel control to show that the CDT obtained from A. actinomycetemcomitans was
      active. The results obtained indicate that the HPDLFs are resistant to the
      cytolethal distending toxin. The possible resistance the HPDLFs have to the CDT
      may stem from the low turnover rate of the fibroblasts. However, further research
      must be completed on this topic.

PMID- 15484635
TI  - Expression of cytolethal distending toxin genes from actinobacillus
      actinomycetemcomitans in escherichia coli.

PMID- 15484636
TI  - Reliability of CCD and CMOS (APS) digital sensors compared with D and E-plus
      speed films in the detection of dental pathology: an in vitro study.

PMID- 15484637
TI  - The new F-speed films in dentistry: a brief review.

PMID- 15484638
TI  - Search for an endogenous collagenase in chicken endochondral bone matrix
      vesicles.
AB  - While isolating matrix vesicles from avian endochondral bone, collagenase
      activity was discovered unexpectedly. The question was raised whether this
      collagenase activity was endogenous or if it was due to the bacterial collagenase
      used to release the matrix vesicles from bone. In related experiments done,
      collagen partially degraded by collagenase mineralized better than undegraded
      collagen. This study would then attempt to show if an endogenous collagenase is
      found, whether it facilitates collagen mineralization by allowing better access
      for matrix vesicles by the "nicking" of collagen. From this two-month study
      evidence was found that an endogenous collagenase as well as a gelatinase was
      present on matrix vesicles. SDS gel electrophoresis and zymography were used to
      determine the presence of collagenases in purified matrix vesicle fractions.
      Western blots with antibodies to bacterial collagenase, matrix metallo
      proteinases 13 (MMP-13), an endogenous collagenase, and MMP-2, an endogenous
      gelatinase, were also done to determine the presence of an endogenous
      collagenase. Another facet was added to this study to determine if contamination
      by exogenous collagenase during matrix vesicle isolation could be removed. From
      the final Western blots done, it was verified that even after exhaustive washings
      of the column and centrifugation, purified matrix vesicles contained
      contaminating bacterial collagenase. Due to the research completed, the matrix
      vesicle isolation protocol was changed from using bacterial collagenase to a
      trypsin isolation method to prevent any exogenous collagenase contamination.

PMID- 15484639
TI  - Interleukin 4 in primary Sjoren's syndrome.

PMID- 15484640
TI  - Spatial organization and biofilm colonization of viridans streptococci.

PMID- 15484641
TI  - Alumni profile: life is.

PMID- 15484643
TI  - Debate needed.

PMID- 15484642
TI  - Speaking of nursing...

PMID- 15484644
TI  - Recovery from work-related trauma by perioperative nurses: the effects of social
      and personal resources.
AB  - The complexities of the recovery process following a traumatic event suggest a
      need to provide support resources that sustain or promote positive perceptions of
      the events. The availability and effectiveness of social support is a function of
      both its content and its capability of responding appropriately to the influence
      of the recovery dynamics in a contingent manner. Further, the quality of recovery
      from work-related trauma is suggested to be a function of the interactive
      processes of the individuals, the organisational environment they work in, and
      the social support provided. Using methodological triangulaton, 213 nurses
      working in rural and metropolitan operating suites were surveyed to assess the
      types, amount and effectiveness of social and personal resources that were used
      following exposure to traumatic work experiences. The findings demonstrate the
      significance of personal and social support resources in assisting perioperative
      nurses to recover from traumatic experiences. A personal sense of coherence and
      emotional support received through disclosure to work colleagues and supervisors
      were the most salutary aspects of support following trauma. The results suggest
      that opportunities should be made available through peer support programs,
      educational programs and professional meetings to better prepare nurses for
      traumatic situations and their aftermath. Furthermore, the work organisation
      needs to be educated in the need for and process of creating sanctuary and
      providing a holistic approach to management. This will then allow individuals,
      such as perioperative nurses, to continue to function at an acceptable level
      during the mitigation of the traumatic incident.

PMID- 15484645
TI  - Challenging the handover ritual. Recommendations for research and practice.
AB  - Communicating nursing care during the patient's total hospital stay is a
      difficult task to achieve within the context of high patient turnover, a lack of
      overlap time between shifts, and time constraints. Clear and accurate
      communication is pivotal to delivering high quality care and should be the gold
      standard in any clinical setting. Handover is a commonly used communication
      medium that requires review and critique. This study was conducted in five acute
      care settings at a major teaching hospital. Using a grounded theory approach, it
      explored the use of three types of handover techniques (verbal in the office,
      tape-recorded, and bedside handovers). Data were obtained from semistructured
      interviews with nurses and participant field observations. Textual data were
      managed using NUD*IST. Transcripts were critically reviewed and major themes
      identified from the three types of handovers that illustrated their strengths and
      weaknesses. The findings of this study revealed that handover is more than just a
      forum for communicating patient care. It is also used as a place where nurses can
      debrief, clarify information and update knowledge. Overall, each type of handover
      had particular strengths and limitations; however, no one type of handover was
      appraised as being more effective. Achieving the multiple goals of handover
      presents researchers and clinicians with a challenging task. It is necessary to
      explore more creative ways of conducting the handover of patient care, so that an
      important aspect of nursing practice does not get classified as just another
      ritual.

PMID- 15484646
TI  - The use of seclusion in the year 2000: what has changed?
AB  - This study was undertaken to examine the perceptions of nurses working in three
      psychiatric settings regarding the effect and use of seclusion. It also aimed to
      identify current practices at these sites in the metropolitan area of Western
      Australia. A total of 78 nurses specialising in mental health care participated
      in the study by completing the 'Attitude towards seclusion survey'. The findings
      of this study indicate that nurses perceive seclusion as an accepted patient
      management strategy. The results also showed that the decision to seclude the
      patient was made by a senior mental health practitioner and that one hour was the
      average time a patient spent in seclusion. It is important to ensure that
      punishment, paternalistic attitudes or punitive actions are not part of clinical
      judgment regarding the use of seclusion. The study has provided evidence of
      nurses' perceptions concerning seclusion and the results highlight the need for
      staff to continue to explore and evaluate issues that lead to seclusion in order
      to facilitate the use of other management strategies that encourage a less
      restrictive environment.

PMID- 15484647
TI  - Analysis of medication incidents and development of a Medication Incident Rate
      Clinical Indicator.
AB  - Most health service organisations depend solely upon spontaneous voluntary
      reporting of medication incidents and a wide variety of available denominators
      are used in order to calculate the Medication Incident Rate (MIR). This paper
      describes how nursing staff and clinical pharmacists reviewed medication incident
      data, revised and established new systems of reporting and developed a clinically
      useful, rate-based MIR Clinical Indicator. In order to make the MIR more
      meaningful, the frequency of occurrence of incidents was considered within the
      context of the total number of medications given to patients. This was achieved
      by undertaking a point prevalence audit of all inpatient medication charts
      (n=372) to determine the total number of doses of medication given to patients
      during a 24 hour period (n=3211). This value was then used as the denominator for
      the MIR indicator. During 1998, a total of 475 medication incidents were
      reported; the average number of incidents was 1.3 per 24 hours. The MIR per 1000
      doses was calculated to be 0.4. In most cases (77%) the incident caused no harm
      to the patient and no change in treatment was required, and the most 'severe'
      category for any incident was that active treatment was required (3% of reported
      incidents). The most common type of incident was the omission of a dose of
      medication (50%). A wide range of drugs were involved in the incidents, most
      commonly morphine (3.4%). The authors consider that the development and use of
      the MIR Clinical Indicator has positively influenced clinical practice in some
      areas at the authors' hospital.

PMID- 15484648
TI  - 'Don't call me sweetie!' Patients differ from nurses in their perceptions of
      caring.
AB  - Effective nursing care relies on congruent nurse-patient perception of needs.
      This study used Q methodology to compare nurses' and patients' perceptions of
      important nursing care behaviour. Q methodology applies statistical analysis to
      qualitative data through a technique of comparative rating using a forced choice
      format. The Care Q Sort, comprising fifty statements of nursing behaviour, was
      administered to nurses and patients from medical wards. Participants ranked the
      nursing behaviours from most to least important. Analysis was completed on 74
      rankings. There was agreement for many behaviours but bimodal distributions for
      nurses' scores for some statements which may be attributable to different
      professional levels. An additional open comments section provided an experiential
      dimension to the research results. The findings will inform nursing practice and
      patient care planning.

PMID- 15484649
TI  - Saving lives with early defibrillation: an overview of automatic external
      defibrillators.

PMID- 15484650
TI  - Nursing informatics: what all nurses need to know and what an expert needs to
      know.

PMID- 15484651
TI  - Modifications to the Periodic Performance Review Acreditation Participation
      Requirement.

PMID- 15484652
TI  - 2005 National Patient Safety Goals matrix.

PMID- 15484653
TI  - Change in the process for organizations in which their survey reports meet a rule
      for conditional accreditation or preliminary denial of accreditation decision.

PMID- 15484654
TI  - Comparison of the full Periodic Performance Review (PPR), Option 1, Option 2, and
      Option 3.

PMID- 15484655
TI  - Standards approved for health care staffing services program.

PMID- 15484656
TI  - Security enhancements made to the Joint Commission Extranet site.

PMID- 15484657
TI  - Compliance data for the Joint Commission's 2003 National Patient Safety Goals.

PMID- 15484658
TI  - Preventing infant death and injury during delivery.

PMID- 15484659
TI  - American Paraplegia Society 1954-2004; our legacy, our future.
AB  - This article chronicles the 50-year history of the American Paraplegia Society
      (APS), the oldest professional organization serving clinicians and researchers in
      the field of spinal cord injury. Formed following World War II by physicians
      striving to provide optimal care to soldiers paralyzed as a result of combat
      injuries, APS continues to serve more than 500 of these professionals today. Its
      support of education and research has helped to position spinal cord medicine in
      the forefront of rapidly advancing fields. The accomplishments of the APS, and
      the individuals whose dedicated efforts were essential to these accomplishments,
      are detailed in this article.

PMID- 15484660
TI  - Gifts from the molecular revolution: protection and repair of the injured spinal
      cord.
AB  - Progress in molecular neurobiology is occurring at an accelerating rate, and the
      newer results carry with them an almost unprecedented degree of specificity.
      This, together with the development of techniques that permit, at least in
      principle, the targeting of DNA, RNA, and proteins in vivo, opens up a spectrum
      of possible new interventions, which almost certainly will have significant
      impact on the search for new therapies, and ultimately cures, for spinal cord
      injury and its consequences. This article outlines several areas of progress,
      based on progress in the author's laboratory, which supports the suggestion that,
      in the foreseeable future, it will be possible to protect and repair the injured
      spinal cord. In particular, this article focuses on progress in 3 interrelated
      areas: (a) neuroprotection (ie, the search for treatments that will protect
      vulnerable axons within the descending and ascending tracts within the spinal
      cord, so that they do not die after the initial traumatic insult); (b)
      restoration of conduction in spinal cord axons that survive the traumatic insult
      but fail to conduct impulses due to damage to their myelin; and (c) the targeting
      of molecules along the pain-signaling pathway, so as to reduce neuronal
      hyperexcitability that produces pain following SCI. Although much work remains to
      be done, we are coming much closer to our goals in each of these areas, and the
      overall objective--of protecting and repairing the injured spinal cord--appears
      achievable.

PMID- 15484661
TI  - Keeping promises: translating basic research into new spinal cord injury
      therapies.
AB  - Centuries of medical wisdom-namely that spinal cord injury (SCI) treatment was
      limited to caretaking until the patients inevitably succumbed to complications
      has given way to tremendous medical and research advancements. The prognosis for
      survival after SCI improved significantly after World War II, leading to the
      largest population of people aging with chronic SCI in history. Despite the
      general lack of optimism for functional recovery after SCI, the spinal cord has
      proven to be one of the most attractive systems for studying central nervous
      system plasticity. Predictions of clinical applications derived from basic
      findings now routinely accompany reports of evidence for spinal axon
      regeneration. This has led to great debate in the SCI research community about
      the level and quality of evidence needed to select truly promising candidate
      therapies. This article reviews the basis for optimism in the new understanding
      of the processes of degeneration after SCI and the mechanisms of regeneration.
      The emphasis is on neuroprotective and reparative strategies emerging from the
      animal literature, and on the steps remaining to be taken to translate these into
      effective clinical trials of new therapies. Examples of the translational process
      in related areas of brain injury and stroke are cited, as well as the specific
      issues relating to the needs of individuals with SCI.

PMID- 15484662
TI  - Update on pharmaceutical trials in acute spinal cord injury.
AB  - OBJECTIVE: To review the major pharmacological trials in acute spinal cord injury
      (SCI) that have been conducted over the past 25 years. METHODS: Review article.
      RESULTS: The publication of the first National Acute Spinal Cord Injury (NASCIS)
      trial in 1984 ushered in the era of pharmacological trials of therapies intended
      to improve neurologic outcome in acute SCI. Subsequent trials of
      methylprednisolone sodium succinate (MPSS) and GM-1 have added to the evidence
      basis that informs the current management practices for acute SCI. CONCLUSION:
      The last 50 years have seen a conceptual shift from the pessimism of the past to
      a cautious optimism that the meager prognosis for neurologic recovery in acute
      SCI will yield to the progress of medical science. Major advances in the
      understanding of primary and secondary injury mechanisms have led to the
      preclinical study of many promising pharmacological therapies, all with the goal
      of improving neurologic outcome. A few of these drugs have stood the test of
      animal model experiments and have made it to the forum of human clinical trials.
      The NASCIS trials of methylprednisolone have been acknowledged widely as the
      first human studies to claim improved neurologic outcome. Although the results of
      these trials remain controversial, the MPSS therapy that they reported has been
      adopted widely by clinicians around the world as the best currently available,
      even if not a consensus "standard of care." Clearly, the challenge for medical
      science remains. The search for effective treatment has only begun.

PMID- 15484663
TI  - SCI clinical research and the American Paraplegia Society at 50 years.

PMID- 15484664
TI  - Fatal spinal cord injury of the 20th president of the United States: day-by-day
      review of his clinical course, with comments.
AB  - BACKGROUND: This article presents the medical history of the 20th president of
      the United States, James A. Garfield, with an emphasis on his spinal cord injury
      (SCI). Numerous references debate the care he received from the medical and
      surgical perspectives, but little has been written about the essential aspect of
      his gunshot wound-namely, the damage to his spinal cord. President Garfield was
      shot in the lumbar spine and was bedridden until he died 80 days following his
      injury. This article contrasts state-of-the-art care in 1881 to today's standards
      of care for SCI. METHOD: Literature review. A record of daily reports of the
      president's condition was analyzed. Comparisons were made between the president's
      care and what is now available. FINDINGS: Although the president had access to
      the best physicians, the chronicle of his course underscores the deficiencies in
      basic medical care, the controversies concerning surgical intervention, and the
      problems inherent in the care of a prominent patient. Press releases did not
      overtly address spinal cord trauma and its complications so as to avoid conveying
      the president's degree of incapacity. Garfield's SCI was documented on autopsy.
      The bullet entered the 10th intercostal space, 3 1/2 inches to the right of the
      spinous processes, fracturing the 11th and 12th vertebrae and nicking the T1 2-L1
      disc. The bullet then passed through the right side of the body of L1 and exited
      the vertebra anteriorly and to the left and lodged behind the pancreas, where it
      was found encased by a firm cyst. CONCLUSION: Deficiencies in general medical
      care and surgical technique at the time contributed to the president's demise.
      This case was marked by controversies that still are debated today-for example,
      whether the bullet should have been removed surgically. Examination of available
      evidence suggests that with today's advances in medical, surgical, and SCI
      medicine, a person with this type of injury would likely survive and be a
      candidate for rehabilitation.

PMID- 15484665
TI  - New rehabilitation interventions in spinal cord injury.
AB  - Progress in the care of people with spinal cord injury (SCI) spans every aspect,
      from research in neuroregeneration to pharmacologic interventions. This article
      focuses on advances in rehabilitation interventions, which have employed
      bioengineering, computerization, and advanced therapeutic techniques. These
      interventions are being applied to functional deficits of the bladder, bowel,
      upper extremities, and respiratory system, as well as to improvements in
      ambulation and mobility. Functional electrical stimulation (FES) is being used to
      augment the function of the lower extremities, the upper extremities (Freehand
      System), and the bowel and bladder (Vocare System). Tendon transfer is a
      reconstructive technique used to improve upper extremity function; it is
      sometimes combined with FES. Body weight-supported treadmill training is being
      used to improve ambulation in people with incomplete SCI, and advances in
      wheelchair technology are expanding options for mobility. Cushion design and
      pressure mapping are modalities being used to reduce the high risk for pressure
      ulcers in the SCI population. Research on shoulder stressors is being applied to
      transfer techniques, exercise regimens, adaptive equipment and wheelchair
      mechanics to minimize shoulder pain, another common complication. The
      effectiveness of rehabilitation interventions needs to be documented by evidence
      based research. Researchers are focusing on the identification of outcomes
      measures that will form the basis for established standards of care for
      individuals with SCI. Perhaps the combination of conventional and newer therapies
      may enhance neurological recovery. Well-designed studies are needed before we can
      make this determination.

PMID- 15484666
TI  - Bioengineering and spinal cord injury: a perspective on the state of the science.
AB  - There is little doubt that as technologic advances become available, people with
      spinal cord injuries (SCIs) are living healthier, more productive, and longer
      lives. Federally and privately funded research, foreign competition, and
      globalization appear to be factors that will drive bioengineering advances within
      the assistive technology (AT) industry. The seeds of bioengineering research are
      likely to contribute to improvements in universal design and the mainstreaming of
      products. The aims of AT have changed tremendously in the past 50 years. Most of
      the federal agencies supporting assistive and rehabilitative technology research
      and development did not exist 50 years ago. Indeed, the leading AT companies all
      were established within the past 50 years. Bioengineering has the potential to be
      to the 21 st century what electronic engineering was to the 20th century.
      Advances in power electronics, telecommunications, controls, sensors, and
      instrumentation have really only just begun to be applied for devices to assist
      people with SCI. Advancing technology for people with SCI represents a
      significant career and business opportunity for engineers who want to serve the
      public good in a meaningful and tangible way.

PMID- 15484667
TI  - Clinical applications of electrical stimulation after spinal cord injury.
AB  - During the last one-half century, electrical stimulation has become clinically
      significant for improving health and restoring useful function after spinal cord
      injury. Short-term stimulation can be provided by electrodes on the skin or
      percutaneous fine wires, but implanted systems are preferable for long-term use.
      Electrical stimulation of intact lower motor neurons can exercise paralyzed
      muscles and reverse wasting; improve strength, endurance, and cardiovascular
      fitness; and may reduce the progression of osteoporosis. Other potential
      therapeutic uses being investigated include reduction of spasticity, prevention
      of deep vein thrombosis, and improvement of tissue health. Pacing of intact
      phrenic nerves in high tetraplegia can produce effective respiration without
      mechanical ventilation, allowing improved speech, increased mobility, and
      increased sense of well-being. Improvement of cough has also been demonstrated.
      Stimulation of intact sacral nerves can produce effective micturition and reduce
      urinary tract infection; it can also improve bowel function and erection. It is
      usually combined with posterior sacral rhizotomy to improve continence and
      bladder capacity, and the combination has been shown to reduce costs of care.
      Electroejaculation can now produce semen in most men with spinal cord injury.
      Significant achievements have also been made in restoring limb function. Useful
      hand grasp can be provided in C5 and C6 tetraplegia, reducing dependence on
      adapted equipment and assistants. Standing, assistance with transfers, and
      walking for short distances can be provided to selected persons with paraplegia,
      improving their access to objects, places, and opportunities that are
      inaccessible from a wheelchair. This review summarizes the current state of
      therapeutic and neuroprosthetic applications of electrical stimulation after
      spinal cord injury and identifies some future directions of research and clinical
      and commercial development.

PMID- 15484668
TI  - Prevention and treatment of heterotopic ossification after spinal cord injury.
AB  - BACKGROUND/OBJECTIVES: Heterotopic ossification (HO) is a frequent, irreversible
      complication after spinal cord injury (SCI). The objective of this article is to
      explain the etiology of HO; present new advances in prevention, diagnosis, and
      management of this complication; and provide a suggested algorithm for clinical
      management. ETIOLOGY: Although still hypothetical, trauma and overexpression of
      bone morphogenic protein(s) in traumatized soft tissue appear to play important
      roles as initiating factors of HO. PREVENTION: Preventive use of nonsteroidal
      antiinflammatory agents (NSAIDs) reduces the incidence of HO by a magnitude of 2
      to 3. MANAGEMENT: Early determination of serum creatine phosphokinase may have a
      diagnostic value in predicting the onset and severity of HO, and an NSAID may be
      added to etidronate therapy in the initial inflammatory phase of HO formation
      until C-reactive protein levels return to normal range. Surgery is indicated in a
      subset of patients, and a regimen that includes radiation therapy may prevent
      postoperative recurrence. CONCLUSION: Significant progress has been made in the
      early prevention and management of HO. Further studies are needed to elucidate
      the etiology.

PMID- 15484669
TI  - Donald Munro Lecture 2003. Neurogenic bladder: past, present, and future.
AB  - The foundation of the management of neurogenic bladder can be attributed to a
      pioneer in spinal cord injury medicine. Dr. Donald Munro, a neurosurgeon, who
      also had experience in urologic surgery, established the first Spinal Cord Injury
      Service of 10 beds in the Boston City hospital in the 1930s. He later became
      adviser to the US Army and the Veterans Administration (VA). On his
      recommendation, paraplegic centers were created in US army hospitals and later in
      the VA hospitals from 1943 to 1945. This article reviews the evolution of the
      management of neurogenic bladder in patients with spinal cord injuries from the
      past century to the present. The role of urodynamics in defining neurologic
      lesions is critical to the appropriate management of the voiding dysfunction. Key
      advances, such as the diagnosis of detrusor sphincter dyssynergia (DSD),
      recognition of its association with autonomic dysreflexia, and its definitive
      management, have been emphasized. The role of transrectal linear array sonography
      using a rectal probe was found useful for defining bladder outlet dysfunction
      during urodynamics. It also helped to recognize secondary bladder neck
      obstruction and diagnose false passages in the urethra. Clean technique
      intermittent catheterization (IC) was evaluated and recommended. In about 28%
      patients with DSD that led to secondary bladder neck obstruction, a consequence
      of IC was reported. Transurethral laser sphincterotomy (TURS) was first reported
      by me in 1991, and later, durable 7-year follow-up results were reported in 78%
      of the first 99 patients. We reported a surgical technique to lengthen the penis.
      We also reported the long-term success with semirigid implants in 92% of patients
      with SCI. This technique helped maintain external condom drainage on a small
      phallus and improved the sex life of patients, as well as their quality of life.
      The author's pertinent areas of interest in the past one-half century were aimed
      at recognizing specific urologic problems associated with neurologic impairment.
      Management was aimed at preventive care, early recognition, and timely management
      to reduce secondary complications and enhance quality of life.

PMID- 15484670
TI  - What should Medicaid look like in 2010?

PMID- 15484671
TI  - The challenges Medicaid faces: funding and its role.

PMID- 15484672
TI  - We ask a lot of Medicaid but don't fund it accordingly.

PMID- 15484673
TI  - Realigning Medicaid means realigning incentives.

PMID- 15484674
TI  - Primary policy considerations: funding and flexibility.

PMID- 15484675
TI  - An optimistic perspective: Medicaid as Cinderella.

PMID- 15484676
TI  - [Antibioprophylaxy in hand surgery: toward a professional consensus].
AB  - Antibioprophylaxy in surgery follows, in France, the guidelines published by the
      French Society of Anesthesia [Societe francaise d'Anesthesie et reanimation
      (SFAR)]. However these guidelines were mostly made for prosthetic and
      traumatologic surgery of the lower limb and guidelines for upper limb and hand
      surgery have been made by extrapolation. The French Society for Surgery of the
      hand has made multiples studies including: a survey to precise the infection rate
      for hand surgery which has been estimated to be around 0.1%. A search in the
      international literature, according to the classification criteria proposed by
      the "Agence Nationale D'accreditation et d'Evaluation Sanitaire (ANAES)" to
      better define correct antibioprophylaxy that should be used in hand surgery.
      Results of those surveys have been presented by national experts at the French
      Society Meeting of 2003. The attendance was given the opportunity to answer
      questions from the experts. A jury was present and its conclusion are reported
      here. Except for total wrist prosthesis and for surgical procedures that last
      more than 2 hours, there are very few indications for an antibioprophylaxy in
      hand surgery. In cases where an antibioprophylaxy is needed, the jury recommends
      that the guidelines proposed by the SFAR, regarding the choice of antibiotics,
      should be followed.

PMID- 15484677
TI  - [Radiological and clinical study of the ulna's end instability after Sauve
      Kapandji procedure].
AB  - The aim of the study was to analyse the ulnar proximal stump's behaviour after
      Sauve-Kapandji procedure. The procedure was performed for post-traumatic
      disorders of the distal radio-ulnar joint. This is a retrospective study of 14
      patients. The mean age of patients at the operation was 49 years. Most of them
      began immediate mobilisation into pronation and supination. After a 5 year follow
      up period, the clinical examination was centred on the ulnar proximal stump. An
      original radiologic study was made with static and dynamic X-Ray. Seven patients
      indicated pain on the ulnar stump during pronosupination. A clunk on the ulnar
      side of the wrist was noticed by three patients and an instability of the ulnar
      stump was observed two times. Clinically, there were a sagittal instability in
      all patients and a frontal instability four times. The sagittal instability was
      confirmed by dynamic X-Ray on each occasion, but the frontal instability was
      never confirmed. Every patient had instability of the ulnar stump; however, it
      was well tolerated. In practice, 12 patients were satisfied or very satisfied
      (86%). Instability of the proximal ulnar stump remains a problem, because it
      occurs despite a strict technique.

PMID- 15484678
TI  - [Desmoid tumors of the shoulder-girdle (report of three cases)].
AB  - The authors report three cases of desmoid tumors of the shoulder-girdle. Through
      these observations and a review of the literature, they underline the specific
      characteristics of the desmoid tumors: the frequency and the seriousness of the
      localisations at the member roots and the great difficulties of the exeresis.

PMID- 15484679
TI  - [The "necktie lasso": a new technique for the simultaneous treatment of
      Wartenberg's sign and claw deformities in the hand due to ulnar nerve palsy].
AB  - The "necktie lasso" is a new technique that allows the simultaneous active
      treatment, of both Wartenberg's sign and claw deformity of the fifth and the
      fourth digits in the hand with ulnar nerve palsy. The flexor sublimis of the
      fourth digit is taken by a palmar approach. It is then divided into two strips up
      to the proximal part of the palm; The radial strip is used as a classical "direct
      lasso" to treat the claw deformity of the fourth digit; The ulnar strip is wound
      around the base of the fifth digit by a palmar and dorsal approaches at the level
      of the proximal phalanx, like a necktie, being medial to its radial pedicle,
      dorsal and superficial to its extensor apparatus, then lateral to its ulnar
      pedicle; It is then recovered in the palm and sutured to itself. From September
      1998 to April 2003, this technique has been used in eight patients aged between
      21 and 35 years old and suffering from post traumatic low ulnar nerve palsy. It
      was always very effective in dealing with Wartenberg's sign: the active adduction
      of the fifth digit appearing at the start of flexion. The claw deformity of the
      fourth and fifth digits was equally actively corrected. No complications are
      reported in this series. With a mean follow-up of 3 years there was no recurrence
      of any of the deformities.

PMID- 15484680
TI  - Deforming chondrosarcoma of the fingers secondary to a long-term enchondromatosis
      of 28 years.
AB  - Enchondromatosis of the hand in the context of the Oilier disease is an
      infrequent pathologie associated with a high rate of malignancy. In this work, we
      present a case with multiple enchondromas affecting mainly the fourth and fifth
      rays of the hand, and with multiple ipsilateral lesions in the foot, sacroiliac
      joint and iliac bone. This patient is, in addition, an unusual case for a long
      term progression (28 years), serious deforming appearance and for the double
      malignant degeneration to chondrosarcoma of the affected fingers. Clinical
      features, tumor factors, criterion of diagnosis and prognosis, surgical strategy
      and follow-up evaluation are analysed, as well as a review of the literature.

PMID- 15484681
TI  - [Semiconstrained total elbow arthroplasty for severe post traumatic ankylosis of
      the elbow: a case-report].
AB  - Post traumatic stiffness in young subjects has been long considered a bad
      indication for total elbow arthroplasty. We present the case of a 48 year old
      woman with an elbow fracture, operated in childhood who developed progressive
      painful stiffness. After treatment with a cemented semi constrained Coonrad
      Morrey total arthroplasty, we have obtained a good result at over 4 years follow
      up. The gain of ROM is 40 degrees, the analogue scale for pain is 2.5/10 and the
      Mayo Clinic Performance Index for the Elbow is 80/100. The subjective impression
      is excellent and there were no complications.

PMID- 15484682
TI  - [Pachydermodactyly: a report of two cases].
AB  - Pachydermodactyly is a superficial benign, symmetrical and painless fibromatosis,
      characterized by a swelling of the proximal interphalangeal joints of the
      fingers. Histological examination shows epidermal hyperplasia increase of dermal
      collagen bundles and an increased number of fibroblasts. We report two cases of
      pachydermodactyly in male teenagers. The aetiology remains unknown.
      Pachydermodactyly has to be distinguished from knuckle pads.

PMID- 15484684
TI  - Leading from within.

PMID- 15484683
TI  - Intracarpal synovitis related to Dacron interposition after trapeziectomy: a
      report of three cases.
AB  - To prevent the mechanical consequences of trapeziectomy, interposition devices
      are promoted, such a Dacron spacer. We report three cases of osteolysis and
      synovitis related to the use of such a device. This phenomenon occurred 4 months
      after insertion and required revision surgery after 9 months of follow-up because
      of pain and extensive osteolysis of the carpal bones. Revision consisted of an
      extended synovectomy, removal of the broken Dacron followed by a ligamentoplasty
      using the Flexor Carpi Radialis. Two years after revision surgery the result was
      satisfactory, with no recurrence of pain or osteolysis. The Dacron device did not
      demonstrate improvement in clinical results after short-term follow-up when
      compared to conventional ligamentoplasty. We recommend cautious use of the Dacron
      device at trapeziectomy and attention must be paid to follow up of the patient.

PMID- 15484685
TI  - The value of the PhD for nursing/midwifery career advancement.

PMID- 15484686
TI  - Computerised Clinical Path Management Systems (CCPMS) in acute settings.

PMID- 15484687
TI  - Assessing Australian undergraduate clinical learning.
AB  - Determining the clinical preparedness of undergraduate nursing students is vital
      in developing graduates who are ready to assume the roles of registered nurses.
      This paper reports findings relating to clinical assessment in Australian
      undergraduate nursing programs. Using data collected in a national survey and
      selected case studies, current assessment practices are described. Although
      students were increasingly exposed to a narrower range of clinical experiences,
      claims to comprehensive preparation of nurses remain prominent. Issues in the
      congruity between assessment methods and purported outcomes of clinical learning
      programs are discussed.

PMID- 15484688
TI  - Circadian rhythm, shiftwork and you!
AB  - Chronobiological knowledge is increasing and the relationship between this
      knowledge and shiftwork is becoming clearer. This, in turn, is highlighting a
      need to facilitate a mix of permanent (day, evening and night) and rotational
      shift systems within individual wards or units. Is it perhaps time to allow
      greater flexibility in how individual nurses deal with the profession's need to
      care for patients throughout the 24 hour period? This review will focus on the 24
      hour day-night or circadian rhythms and the consequences of the disruption of
      these rhythms as nurses undertake shiftwork and other activities which demand
      efficient functioning at times when an individual's circadian rhythms are
      expecting them to be at rest. As disruption of these rhythms is essentially
      unavoidable when 24 hour care is required, the choice becomes one of determining
      a preference for tolerable rhythm desynchrony and shorter more frequently
      occurring episodes of night work, or some degree of rhythm synchrony and
      adaptation during slightly longer but less frequent episodes of rhythm
      disruption.

PMID- 15484689
TI  - National drug policy: implications of the 'tough on drugs' ideology.
AB  - Australia has emerged over the last decade as a world leader in drug policy.
      According to Single and Rohl (1997 pvii) Australia's National Drug Strategy 'has
      been characterised by a unique combination of features which have brought it
      international attention and acclaim'. The strength of Australia's policy has been
      its emphasis on both licit and illicit drugs, and also its clear articulation of
      harm minimisation as a guiding principle in all areas of action. The key policy
      goals recognised the harm associated with all substances and sought results in
      key areas of alcohol-related problems, tobacco-related problems, under-age
      consumption, prescription medication problems and illicit drug use. However,
      Australia has a new drug policy document for the new millennium, The National
      Drug Strategic Framework 1998 - 2002. As a result of a conservative influence in
      national politics, this framework has moved from the harm minimisation philosophy
      to a moralistic 'tough on drugs' philosophy that stresses zero tolerance, law
      enforcement and abstinence. There is a risk that Australia will experience an
      increase in adverse health, social and economic consequences as a result of this
      new policy direction. Nurses need to think critically about the 'tough on drugs'
      ideology. There is a risk that significant adverse affects may occur for their
      drug-using patients as a result of this policy change. In their practice, nurses
      need to challenge the validity of a punitive response, and to commit themselves
      to improving the health and safety of the illicit drug-using community.

PMID- 15484690
TI  - A practice-research model for collaborative partnership.
AB  - The ability to integrate education, practice and research initiatives is well
      documented and the nursing literature presents several collaborative models that
      have emerged between educational institutions and service agencies to achieve
      this aim. However, a collaborative partnership agreement does more than integrate
      these initiatives; it is a vehicle by which the theory-clinical practice gap is
      bridged and best practice outcomes are achieved. This paper outlines an
      innovative collaborative partnership agreement between Fremantle Hospital and
      Health Service and Curtin University of Technology in Perth, Western Australia.
      The partnership engages academics in the clinical setting in two formalised
      collaborative appointments. This partnership not only enhances communication
      between educational and health services, but fosters the development of nursing
      research and knowledge. The process of the collaborative partnership agreement
      involved the development of a Practice-Research Model (PRM) of collaboration.
      This model encourages a close working relationship between registered nurses and
      academics, and has also facilitated strong links at the health service with the
      Nursing Research and Evaluation Unit, medical staff and other allied health
      professionals. Links have also been established with other health services and
      agencies in the metropolitan area. The key concepts exemplified in the
      application of the model include practice-driven research development, collegial
      partnership, collaborative ownership and best practice. Many specific outcomes
      have been achieved through implementation of the model, but overall the
      partnership between registered nurses and academics in the pursuit of research to
      support clinical practice has been the highlight. This has resulted in changes
      and innovations in current nursing practice and, importantly, dissemination of
      best practice outcomes.

PMID- 15484691
TI  - Nurse researcher: always a researcher, sometimes a nurse.
AB  - A number of theoretical papers have highlighted the concept of the duality and
      dichotomy of roles when nurses are carrying out research in the clinical arena.
      The conflicts that can occur are between the roles of researcher and nurse and in
      the balance between research integrity and the welfare of the individual. There
      are various personal accounts in the literature of nurse researchers' experiences
      of unclear role expectations when doing research. There appears to be no
      consensus on how nurse researchers should handle these varying expectations. No
      comparative analysis of the reflections of a collective of nurse researchers on
      role expectations in different clinical contexts was found in an extensive
      literature search. This paper attempts to do this by analysing stories of a small
      group of nurse researchers in different clinical contexts. Data were analysed
      from written stories and audio-taped interviews with nurse researchers about
      moving from the researcher to the nurse role in doing clinical research. Thematic
      analysis indicated that the participants' reactions could be classified as either
      those of a nurse researcher, always the researcher, or as the nurse researcher,
      sometimes the nurse. There were no distinct differences in relation to research
      topic, methodology or context. The study highlights the fact that nurses need
      better research education, team and management support when conducting research
      and opportunities to debrief after encountering mixed role expectations in the
      field. Open debate amongst nurse researchers about role delineation is essential
      to both novices and experts for them to share their experiences and their
      solutions.

PMID- 15484692
TI  - Pressure ulcers: how do we reduce the incidence?

PMID- 15484693
TI  - The World Wide Web and consumer health information.

PMID- 15484694
TI  - Human neural stem cells genetically modified for brain repair in neurological
      disorders.
AB  - Existence of multipotent neural stem cells (NSC) has been known in developing or
      adult mammalian CNS, including humans. NSC have the capacity to grow indefinitely
      and have multipotent potential to differentiate into three major cell types of
      CNS, neurons, astrocytes and oligodendrocytes. Stable clonal lines of human NSC
      have recently been generated from the human fetal telencephalon using a
      retroviral vector encoding v-myc. One of the NSC lines, HB1.F3, carries normal
      human karyotype of 46XX and has the ability to self-renew, differentiate into
      cells of neuronal and glial lineages, and integrate into the damaged CNS loci
      upon transplantation into the brain of animal models of Parkinson disease, HD,
      stroke and mucopolysaccharidosis. F3 human NSC were genetically engineered to
      produce L-dihydroxyphenylalanine (L-DOPA) by double transfection with cDNA for
      tyrosine hydroxylase and guanosine triphosphate cylohydrolase-1, and
      transplantation of these cells in the brain of Parkinson disease model rats led
      to L-DOPA production and functional recovery. Proactively transplanted F3 human
      NSC in rat striatum, supported the survival of host striatal neurons against
      neuronal injury caused by 3-nitropro-pionic acid in rat model of HD.
      Intravenously introduced through the tail vein, F3 human NSC were found to
      migrate into ischemic lesion sites, differentiate into neurons and glial cells,
      and improve functional deficits in rat stroke models. These results indicate that
      human NSC should be an ideal vehicle for cell replacement and gene transfer
      therapy for patients with neurological diseases. In addition to immortalized
      human NSC, immortalized human bone marrow mesenchymal stem cell lines have been
      generated from human embryonic bone marrow issues with retroviral vectors
      encording v-myc or teromerase gene. These immortalized cell lines of human bone
      marrow mesenchymal stem cells differentiated into neurons/glial cells, bone,
      cartilage and adipose tissue when they were grown in selective inducing media.
      There is further need for investigation into the neurogenic potential of the
      human bone marrow stem cell lines and their utility in animal models of
      neurological diseases.

PMID- 15484695
TI  - Morphology of proliferating and non-proliferating tumor cell nuclei in
      glioblastomas correlates with preoperative data from proton-MR-spectroscopy.
AB  - In contrast to the growing interest in proton-MR-spectroscopy (1HMRS) for
      preoperative examination of patients with brain tumors, there is nearly no
      knowledge about a correlation between data from 1HMRS and histomorphology as
      confirmed by quantitative morphological methods. Whether a correlation can be
      confirmed between data from 1HMRS and quantitative histomorphology of
      glioblastomas representing the most frequent type of brain tumors was
      investigated in the present study. Furthermore, it was of interest, whether
      correlations between spectroscopic data and histomorphology can be confirmed for
      proliferating and non-proliferating tumor cell nuclei independently. Using
      stringent inclusion criteria for this study, 24 patients were investigated by
      means of preoperative 1HMRS and by means of digital image analysis of paraffin
      sections from the surgical specimen. Proliferating and non-proliferating tumor
      cell nuclei were investigated separately in the region with the highest
      proliferative activity in each tumor using immunohistological staining for the
      proliferation marker Ki67. Main results showed highly significant correlations
      between total creatine and variables of nuclear size, as well as correlations
      between choline and variables of nuclear shape. These results were confirmed for
      both proliferating and non-proliferating tumor cell nuclei. A significant
      correlation between N-acetyl-aspartate level and topometric variables (number of
      neighbors per nucleus, variables describing distances between tumor cell nuclei)
      was confirmed for proliferating tumor cell nuclei. Discriminant analysis provided
      a good separation of cases with high and with low values for these spectroscopic
      variables based on histomorphometric data. In conclusion, the results confirm a
      direct correlation between data from preoperative 1HMRS and histomorphological
      characteristics of glioblastomas supporting the biological relevance of
      spectroscopic data for the examination of brain tumor patients.

PMID- 15484696
TI  - Conditional entropy as an indicator of pleomorphism in astrocytic tumors.
AB  - The entropies of nuclear arrangements as an indicator of pleomorphism are
      assessed using a morphometric method. Sixty astrocytic tumors (grades I, II, III
      and IV; 15 cases each) were reviewed and analyzed. All slides were stained with
      HE and MIB-1 antibody. The MIB-1 labeling index (LI) was assessed by counting
      nuclei under a microscope. Images of HE-stained slides were digitized and
      segmented using the watershed algorithm. Then, six nuclear parameters were
      measured automatically: (i) the number of total nuclei in the image, (ii)
      percentage of total nuclear area in the image, (iii) the mean area of the
      nucleus, (iv) the standard deviation of the area of the nucleus, (v) the entropy
      of nuclear arrangement (Entropysimple), and (vi) conditional entropy of nuclear
      arrangement (Entropyconditional). Entropysimple was defined according to the area
      of the nucleus and Entropyconditional was defined according to both the area of
      the nucleus and the area of its neighboring nuclei. Image processing and image
      analysis were performed with public domain software developed in the laboratory.
      Segmentation of the images resulted in inappropriate segmentation in a few
      percent of the images. The measurements obtained for each parameter were
      classified using discriminant analysis. The percentage of correct classification
      with Entropyconditional was 62%, which was the highest value among all the
      measurements. Classification based on the combination of all measurements
      resulted in a rate of correct classification of 88%. Thus, conditional entropy of
      nuclear arrangement is useful for grading of astrocytic tumors and it is proposed
      as an indicator of pleomorphism.

PMID- 15484697
TI  - Active clearance of human amyloid beta 1-42 peptide aggregates from the rat
      ventricular system.
AB  - A major constituent of SP in the brains of Alzheimer's disease is 39-43 amino
      acid peptide called beta-amyloid peptide (Abeta). Recent data have demonstrated
      that Abeta has a strong tendency to form insoluble aggregates and that toxic
      effects of Abeta is based on its aggregation. In the current study, 100 microg of
      human synthetic Abeta 1-42 (sAbeta 1-42) was infused into the lateral ventricle
      of rat brain using a short-term infusion model. At 2 or 7 days following the
      infusion, sAbeta 1-42 was found to form insoluble aggregates, scattering
      throughout the entire ventricular systems. The sAbeta 1-42 aggregates were
      partially engulfed by phagocytic cells and deposited at the meningeal vessels or
      the choroid plexuses. However, these deposits mostly disappeared from the
      ventricles by 28 days post-infusion. Here, it is reported for the first time that
      considerable amounts of sAbeta 1-42 are almost cleared from the rat ventricular
      system by the mononuclear phagocytic system.

PMID- 15484698
TI  - Cyclooxygenase-2 in oligodendroglioma: possible prognostic significance.
AB  - Cyclooxygenase-2 (COX-2) is the inducible form of the enzyme involved in the
      first two steps of the prostaglandins and thromboxane synthesis. Up-regulation of
      COX-2 is demonstrated in tumors where it can modulate tumoral progression,
      metastasis, multidrug resistance and angiogenesis. Selective COX-2 inhibitors are
      seen with growing interest in the tumors treatment. This present study reviews
      the COX-2 expression in 32 primary oligodendrogliomas (24 WHO II; eight WHO III)
      and two glioblastomas with prominent oligodendroglial features (WHO IV).
      Immunohistochemical results were compared with survival in order to verify the
      COX-2 prognostic significance. COX-2 positivity was found in 44% tumors. Median
      survival of the patients with a COX-2 positive lesion was 37 months; median
      survival of the patients with a COX-2 negative lesion was 93 months (P =0.010).
      Twenty-nine percent WHO grade II tumors, 87% WHO grade III, 50% WHO grade IV
      resulted COX-2 positive (P =0.016). In patients affected by WHO grade II
      oligodendroglioma, median survival was 24 and 96 months, respectively, in COX-2
      positive and negative lesions (P =0.012). In conclusion, even if further studies
      on different, homogeneous and larger series in vivo are certainly necessary, it
      is believed that COX-2 could really have a prognostic value and can be considered
      as a possible therapeutic opportunity.

PMID- 15484699
TI  - Expression of insulin-like growth factors in remyelination following ethidium
      bromide-induced demyelination in the mouse spinal cord.
AB  - Insulin-like growth factors, IGF-I and IGF-II, play important roles in
      development and myelination in the CNS, but little is known about the response of
      IGF after demyelination. The present study investigated the expression of IGF and
      their cognitive receptors in the process of remyelination following ethidium
      bromide (EBr)-induced demyelination in the adult mouse spinal cord. The present
      results, in a quantitative real-time PCR, showed significant increases in the
      levels of the mRNA for both IGF-I and IGF-II during both the demyelination and
      remyelination stages. The levels of IGF-I receptor (IGF-IR) mRNA increased from
      10 days to 4 weeks after the EBr injection. The levels of IGF-II receptor (IGF
      IIR) mRNA decreased for 6 days and then increased 10 days after the EBr
      injection. In situ hybridization studies showed the cells expressing IGF-I mRNA
      to be mainly macrophage-like cells, while those expressing IGF-II mRNA were
      predominantly Schwann cell-like cells invading the demyelinating lesion. The
      immunoreactivity for the IGF-IR and IGF-IIR increased in various kinds of cells
      within and around the demyelinating lesions from 6 days to 4 weeks after the EBr
      injection. These results suggest that locally produced IGF could partly be
      involved in some mechanisms underlying remyelination processes following the EBr
      induced demyelination in the mouse spinal cord.

PMID- 15484700
TI  - Three-dimensional structural changes in cerebral microvessels after transient
      focal cerebral ischemia in rats: scanning electron microscopic study of corrosion
      casts.
AB  - Pathological changes of cerebral microvessels in transient ischemia were
      investigated by scanning electron microscopy of vascular corrosion casts. Wistar
      rats were treated with middle cerebral artery (MCA) occlusion for 30 min, 1 h, 3
      h, 4 h, 5 h or 7 h and subsequent reperfusion for 2 h. The ultrastructures of the
      cast were observed and computer-aided montage micrographs were obtained for
      visualization of the whole microvasculature in the ischemic brain hemisphere.
      Avascular areas representing ischemic areas were detected in the frontotemporal
      cortex and caudate putamen in the groups from 30 min to 5 h occlusion.
      Extravasation of the resin, which probably corresponded to the leakage of plasma
      or hemorrhage, was seen as spheroidal, conglomerative, large massive and worm
      like types. The spheroidal type, which probably indicated a small leakage or
      minor hemorrhage, began to appear in the 30-min occlusion group. The
      conglomerative type, which probably indicated a larger leakage or moderate
      hemorrhage, appeared in the 3- to 5-h occlusion groups. The large massive and
      worm-like types, which probably indicated a significant hemorrhage, appeared in
      the 4- and 5-h occlusion groups. The number of these extravasations increased
      significantly in the 4-h occlusion group. Arterioles near the avascular area
      frequently showed vasospastic appearances, such as corrugations, fusiform
      indentations of endothelial nuclei, continuous circulatory constrictions and
      severe narrowing with interrupted branches. Arteriolar vasospasm possibly caused
      prolonged hypoperfusion even if reperfusion was achieved. The capillaries had a
      thin stringy appearance in the 4- and 5-h occlusion groups. These changes seemed
      to relate closely with increased intracranial pressure by brain edema or
      hemorrhage. The present study suggested that the risk of brain edema or
      hemorrhagic infarction increased beyond 3 h of MCA occlusion, and vasospasm of
      the arterioles might participate in stroke pathophysiology.

PMID- 15484701
TI  - Sporadic amyotrophic lateral sclerosis of long duration mimicking spinal
      progressive muscular atrophy exists: additional autopsy case with a clinical
      course of 19 years.
AB  - This report concerns an autopsy case of sporadic amyotrophic lateral sclerosis
      (ALS) clinically diagnosed as having spinal progressive muscular atrophy (SPMA).
      The patient was a Japanese woman without hereditary burden. She developed muscle
      weakness in the distal part of the right upper extremity at age 52, followed by
      muscle weakness in the left upper extremity and lower extremities at age 54 and
      64, respectively. At age 66 she could not walk, even with assistance.
      Fasciculation and atrophy of the tongue appeared at age 68, followed by dysphagia
      and dysarthria at age 70. She died of respiratory disturbance at age 71. During
      the clinical course, neurological examination revealed neither Babinski sign nor
      hyperreflexia. No respirator administration was performed throughout the clinical
      course. Neuropathological examination disclosed not only neuronal loss with
      gliosis in the hypoglossal nucleus and anterior horns of the spinal cord, but
      also loss of Betz cells and degeneration of the pyramidal tract. Based on these
      clinicopathological findings and a literature review of sporadic autopsy cases of
      ALS with long clinical course (10 years or more), including four cases without
      pyramidal signs, we believe that sporadic ALS of long clinical course mimicking
      SPMA exists.

PMID- 15484702
TI  - Pathological and immunohistochemical findings of an autopsy case of adult
      moyamoya disease.
AB  - Moyamoya disease is vaso-occlusive disease involving the arteries of the circle
      of Willis that is accompanied by a compensatory recruitment of a vascular
      network. The pathological and immunohistochemical findings of an autopsy case of
      hemorrhagic moyamoya disease in a 69-year-old woman are described in the present
      report. The autopsy findings of the brain revealed cerebral and intraventricular
      hemorrhage with edema. The left anterior cerebral artery, bilateral middle
      cerebral arteries and left posterior cerebral artery were marked narrowing, and
      the other arteries revealed mild narrowing. Microscopically, the arteries of the
      circle of Willis showed narrowed lumen, fibrocellular intimal thickening, marked
      tortuousness of internal elastic lamina and attenuation of media. The thickened
      intima was composed of smooth muscle cells. The vessels with dilated or irregular
      shaped lumen suggested abnormal vascular networks demonstrated by angiography. In
      this case, no correlation between the abnormal vascular network and expression of
      VEGF or VEGF receptor was disclosed. It was hypothesized that abnormal vascular
      networks might be composed of collateral vessels in relation to various
      pathological changes of the arteries, such as occlusion and stenosis, and
      intracranial hemorrhage in patients with moyamoya disease might occur as a result
      of rupture of arteries including abnormal vascular networks.

PMID- 15484703
TI  - Chordoid meningioma: rare variant of meningioma.
AB  - Chordoid meningioma is a rare variant of meningioma that bears a striking
      histological resemblance to chordoma and has greater likelihood of recurrence.
      Although most meningiomas occur in the intracranial, orbital and intravertebral
      cavities, rare meningiomas have been reported in extracranial organs; thus, it is
      important to be able to distinguish them from other neoplasms that have similar
      histology but different biological behavior and therapies. A case of chordoid
      meningioma in a 48-year-old woman who did not have Castleman's syndrome is
      described in the present report. The patient presented with a mass in her left
      frontoparietal region, and had been suffering from headaches for many years.
      Magnetic resonance imaging of the brain demonstrated an expansive lytic lesion in
      the squamous portion of the left temporal bone. The lesion extended in both
      directions. Histological examination of the surgical specimen revealed a tumor
      composed of cords and nests of eosinophilic vacuolated cells embedded in a myxoid
      matrix. A typical meningiomatous pattern was observed focally, and positive
      staining of the tumor cells for vimentin and epithelial membrane antigen
      confirmed the diagnosis of chordoid meningioma.

PMID- 15484704
TI  - Multinucleated astrocytes in old demyelinated plaques in a patient with multiple
      sclerosis.
AB  - A 51-year-old woman with MS of 26 years duration is reported. The patient's MS
      history began at the age of 25 years with an initial relapsing-remitting course,
      followed by slow progression without distinct relapses. She became bed-ridden at
      the age of 40 years. A post-mortem examination revealed numerous demyelinated
      plaques that exhibited fibrillary gliosis with Rosenthal fibers, but without
      lymphocytic cuffing or foamy macrophages. Activated microglia were found mainly
      in the marginal portion of the plaques. These plaques were consistent with so
      called 'slowly expanding plaques'. Interestingly, multinucleated astrocytes were
      observed within the plaques, being more numerous in the area where microglial
      infiltration had occurred. These findings suggest that mild persistent
      inflammatory processes are present even in old plaques and that certain
      inflammatory stimuli cause multinucleation of astrocytes. This might explain the
      gradual deterioration without definite relapses observed in the late stage of MS.

PMID- 15484705
TI  - Neuropathological diagnostic criteria for Alzheimer's disease.
AB  - Neuropathological diagnostic criteria for Alzheimer's disease (AD) are based on
      tau-related pathology: NFT or neuritic plaques (NP). The Consortium to Establish
      a Registry for Alzheimer's disease (CERAD) criterion evaluates the highest
      density of neocortical NP from 0 (none) to C (abundant). Clinical documentation
      of dementia and NP stage A in younger cases, B in young old cases and C in older
      cases fulfils the criterion of AD. The CERAD criterion is most frequently used in
      clinical outcome studies because of its inclusion of clinical information. Braak
      and Braak's criterion evaluates the density and distribution of NFT and
      classifies them into: I/II, entorhinal; III/IV, limbic; and V/VI, neocortical
      stage. These three stages correspond to normal cognition, cognitive impairment
      and dementia, respectively. As Braak's criterion is based on morphological
      evaluation of the brain alone, this criterion is usually adopted in the research
      setting. The National Institute for Aging and Ronald and Nancy Reagan Institute
      of the Alzheimer's Association criterion combines these two criteria and
      categorizes cases into NFT V/VI and NP C, NFT III/IV and NP B, and NFT I/II and
      NP A, corresponding to high, middle and low probability of AD, respectively. As
      most AD cases in the aged population are categorized into Braak tangle stage IV
      and CERAD stage C, the usefulness of this criterion has not yet been determined.
      The combination of Braak's NFT stage equal to or above IV and Braak's senile
      plaque Stage C provides, arguably, the highest sensitivity and specificity. In
      future, the criteria should include in vivo dynamic neuropathological data,
      including 3D MRI, PET scan and CSF biomarkers, as well as more sensitive and
      specific immunohistochemical and immunochemical grading of AD.

PMID- 15484706
TI  - A 32-year-old man with left temporal lobe tumor.

PMID- 15484707
TI  - A 58-year-old woman presents with paraplegia of three years duration.

PMID- 15484708
TI  - Heterotopic cingulum.

PMID- 15484709
TI  - Depolarization-activated K+ currents of the bushy neurones of the rat cochlear
      nucleus in a thin brain slice preparation.
AB  - Depolarization-activated outward currents of bushy neurones of 6-14-day-old
      Wistar rats have been investigated in a brain slice preparation. Under current
      clamp, the cells produced a single action potential at the beginning of
      suprathreshold depolarizing current steps. On voltage-clamp depolarizations, the
      cells produced a mixed outward K+ current that included a component with rapid
      activation and rapid inactivation, little TEA+ sensitivity, a half-inactivation
      voltage of -77 +/- 2 mV (T = 25 degrees C; n = 7; Mean +/- S.E.M.) and single
      exponential recovery from inactivation (taurecovery= 12 +/- 1 ms at -100 mV;
      n=3). This transient component was identified as an A-type K+ current. Bushy
      cells developed a high-threshold TEA-sensitive K+ current that exhibited less
      prominent inactivation. These characteristics suggested that this current was
      associated with the activation of delayed rectifier K+ channels. Bushy neurones
      also possessed a low-threshold outward K+ current that showed partial
      inactivation and high 4-aminopyridine sensitivity. Part of this current component
      was blocked by 200 nmol/l dendrotoxin-I. Application of 100 micromol/l 4
      aminopyridine changed the firing behaviour of the bushy neurones from the primary
      like pattern to a much less rapidly adapting one, suggesting that the low
      threshold current might have important roles in maintaining the physiological
      function of the cells.

PMID- 15484710
TI  - Echocardiographic characteristics in adolescent junior male athletes of different
      sport events.
AB  - The purpose of this study was to examine the effects of different sport
      activities on cardiac adaptation. Echocardiographic data of 137 athletes and 21
      non-athletes were measured and compared in two age groups 15-16 and 17-18 years
      of age. Athletes belonged into three groups according to their sports activity
      (endurance events, power athletes, ball game players). The observed variables
      were related to body size by indices in which the exponents of the numerator and
      the denominator were matched. Left ventricular hypertrophy was manifest in all
      athletic groups. Power athletes had the largest mean left ventricular wall
      thickness (LVWTd) in both age groups. In the older age group differences between
      the athletic groups were smaller, but the endurance and power athletes had
      significantly higher wall thickness. Left ventricular internal diameter (LVIDd)
      was the largest in the endurance athletes, while mean relative muscle mass (LVMM)
      was the largest in the power athletes. LVMM of the older endurance athletes was
      significantly larger. Muscular quotient (MQ) was the highest in the endurance
      athletes; in the 17-18-year group there was no inter-event difference.
      Bradycardia was most manifest in the endurance athletes and ball game players,
      power athletes had higher resting heart rates than non-athletic subjects. It can
      be inferred that endurance training induces firstly an enlargement of the left
      ventricle what is then followed by an increase of muscle mass. In the studied
      functional and regulatory parameters no difference was found between the athletic
      and non-athletic groups.

PMID- 15484711
TI  - Effects of mebudipine and dibudipine, two new calcium channel blockers, on guinea
      pig isolated common bile duct.
AB  - The inhibitory effects of calcium channel blockers; nifedipine and two new
      compounds, mebudipine and dibudipine, on contractions of isolated guinea-pig
      common bile duct were investigated. All the compounds tested induced a
      concentration-dependent reduction of the amplitude of contractile response to
      electrical stimulation and all the compounds displaced concentration-response
      curve of calcium chloride to the right in a concentration-dependent manner. The
      pIC50 values for these compounds acting on electrically stimulated common bile
      duct were calculated as: dibudipine: 8.50 +/- 0.17; mebudipine: 8.27 +/- 0.20;
      nifedipine: 7.96 +/- 0.07. The compounds also antagonized the contractile
      response of K+-depolarized guinea-pig common bile duct to cumulative
      concentration of calcium. However the inhibitory effect of these compounds were
      not significantly different.

PMID- 15484712
TI  - Scanning laser polarimetry of retinal nerve fibre layer thickness after laser
      assisted in situ keratomileusis (LASIK): stability of the values after the third
      post-LASIK month.
AB  - BACKGROUND: Monitoring the retinal nerve fibre layer thickness (RNFLT) is
      essential in the diagnosis and treatment of glaucoma. In a previous study we
      found that a decrease of the polarimetric RNFLT observed in the early period
      after laser-assisted in situ keratomileusis (LASIK) disappears or tends to
      disappear by the third post-LASIK month. PURPOSE: To study the stability of the
      "recovered" polarimetric retardation values between the third and twelfth month
      after LASIK. METHODS: Scanning laser polarimetry (SLP) with the classic GDx Nerve
      Fiber Analyzer was performed on 13 consecutive healthy subjects with no eye
      disease who underwent LASIK for ametropia correction. Measurements were performed
      preoperatively, then at 3 and 12 months postoperatively. RESULTS: Inferior,
      temporal and nasal average thickness as well as ellipse average thickness and
      average thickness showed no difference among the three time points (ANOVA, p >
      0.05). Superior average thickness was significantly smaller both at three months
      (Sheffe test, p =0.008) and 12 months (p =0.006) than before LASIK. However, no
      difference was seen between the values measured at three months and at 12 months
      after LASIK (p =0.997). A statistically significant interaction between treatment
      type (myopic or hyperopic correction) and the change of retardation was found for
      the superior average thickness (two-way ANOVA, p =0.016). In this quadrant the
      RNFLT values of the myopic eyes decreased between the baseline and the month 3
      measurements but became stable after that; the retardation of the hyperopic eyes
      remained unchanged throughout. CONCLUSION: RNFLT measured with the classic GDx
      device after LASIK shows transient changes probably due to the LASIK-induced
      alteration of the polarization and the healing process. The polarimetric RNFLT
      values, however, become stable by the third post-LASIK month, and show no further
      change until the end of the first year after LASIK. Baseline SLP measurements for
      long-term glaucoma follow-up can be obtained from the third post-LASIK month
      onwards.

PMID- 15484713
TI  - Pathomechanism of chronic venous insufficiency and leg ulcer.
AB  - Uniform view of chronic venous diseases has been formed in the last 3 decades.
      Chronic venous insufficiency (CVI) is a functional disorder of the venous system
      of the lower limb. The basis of the pathology is always the venous hypertension
      caused by valvular insufficiency and reflux with or without venous outflow
      obstruction. Epifascial, subfascial and transfascial forms of CVI can be
      distinguished. In the practice these forms are almost always combined. The
      consistent venous hypertension is the initiating factor in alterations in the
      microcirculation which leads to skin changes and venous ulceration. The precise
      mechanism of the development of venous leg ulcer is still uncertain. A recent
      hypothesis suggests that leukocytes are trapped in the capillaries and attaching
      to the endothel they become activated and release proteolytic enzymes, free
      radicals which have destructive effects on lipid membranes, proteins as well as
      on many connective tissue compounds. The endothelium plays active role in the
      complex mechanism. Increased expression of tissue metalloproteinases has been
      observed in the periulcer skin. The presence of perivascular leukocyte
      infiltration and fibrin cuff is a reflexion of an inflammatory process. The
      clinical stages of CVI are likely to be the results of a systemic inflammatory
      response to a period of venous hypertension.

PMID- 15484715
TI  - Promoting physical activity in medical education. Mini-review.
AB  - The challenges in public health associated with sedentary lifestyle underline the
      need to prepare physicians to give appropriate medical counselling and exercise
      prescription. In addition, the medical students' lifestyle and physical fitness
      suggest changes in medical education. Physical education as a criterion subject
      in our medical school curriculum serves to direct students' attitude toward
      regular physical activity. The knowledge of exercise counselling is promoted by a
      credit course of human movement sciences.

PMID- 15484714
TI  - A fully symbolic design and modeling of nonlinear glucose control with Control
      System Professional Suite (CSPS) of Mathematica.
AB  - In this case study a fully symbolic design and modeling method are presented for
      blood glucose control of diabetic patients under intensive care using
      Mathematica. The analysis is based on a modified two-compartment model proposed
      by Bergman et al. The applied feedback control law decoupling even the nonlinear
      model leads to a fully symbolic solution of the closed loop equations. The
      effectivity of the applied symbolic procedures being mostly built-in the new
      version of Control System Professional Suite (CSPS) Application of Mathematica
      have been demonstrated for controller design in case of a glucose control for
      treatment of diabetes mellitus and also presented for a numerical situation
      described in Juhasz. The results are in good agreement with the earlier presented
      symbolic-numeric analysis by Benyo et al.

PMID- 15484716
TI  - A historical chronology of teaching physiological sciences to medical students in
      Hungary.
AB  - Starting from the second half of the 18th century, a brief chronology of teaching
      medical physiology and pathophysiology in Hungary is given in this article. Even
      when the major milestones of this history are only identified, one can recognize
      several significant achivements that may inspire the present and coming
      generations to develope and enrich this inheritance of high values. These
      achivements involve--inter alia--influential scientific "schools" founded by
      eminent professors, outstanding institutions of basic medicine, recognition of
      the relevance of the integrative approach in medical education, close
      relationship between teaching and scientific research, high-standard theoretical
      and practical training, teaching based on excellent domestic and foreign
      textbooks, extensive international relationships and experience.

PMID- 15484717
TI  - Effects of body weight at, and lighting regimen and growth curve to, 20 weeks on
      laying performance in broiler breeders.
AB  - 1. A total of 4000 Ross broiler breeders were reared to a 20-week target body
      weight of 1.55, 2.16 (standard), 2.50 or 2.84 kg, using either a convex or
      concave growth curve. Each treatment group was either exposed to a conventional
      broiler breeder lighting regimen, with a series of weekly one-hour increments in
      photoperiod from 8h at 19 weeks to a 16-h maximum, or maintained from 4d on a 17
      h photoperiod. 2. Each 100 g increment in body weight at 20 weeks was associated
      with a significant increase of 0.55 kg in cumulative food intake, and a 1.5-d
      advance in sexual maturity. However, leaner body weights at 20 weeks resulted in
      smaller body weight gains between 20 and 60 weeks (-2.4 g/d/kg body weight at 20
      weeks), and an increased production of double-yolked eggs. Neither egg production
      nor mean egg weight was affected by 20-week body weight. 3. Birds fed to produce
      more rapid early growth had higher feed intakes to 20 weeks, but reached sexual
      maturity 7 d later than birds permitted accelerated growth from 15 weeks. Growth
      curve did not influence body weight gain in lay, egg production or mean egg
      weight. 4. Birds maintained on 17-h photoperiods reached sexual maturity 27 d
      later, produced 7 fewer eggs to 60 weeks, and had a mean egg weight 1.2 g heavier
      than birds photostimulated at 19 weeks. Lighting treatment did not affect food
      intake to 20 weeks, the proportion of double-yolked eggs or body weight gain
      between 20 and 60 weeks. 5. Birds fed to have a faster growth early in the
      rearing phase and maintained on 17-h photoperiods produced 11 fewer eggs than
      those fed to have accelerated growth at the end of the rearing phase, yet there
      was only one egg difference between the growth-curve groups for the
      conventionally lighted birds, which was not significant. 6. The earlier sexual
      maturity of the conventionally lighted birds compared with those maintained on 17
      h photoperiods either indicates that broiler breeders require an increment in
      photoperiod to stimulate rapid gonadal development or that broiler breeders
      exhibit juvenile photorefractoriness that takes longer to be dissipated when
      birds are not given a period of short days. 7. The findings suggest that a
      nutritional stimulus late in rearing is only necessary for satisfactory egg
      production if birds have not received a concurrent increment in photoperiod.

PMID- 15484718
TI  - Individual production differences do not explain cannibalistic behaviour in
      laying hens.
AB  - 1. Sixty-three laying hens were collected from 5 commercial farms experiencing
      outbreaks of cannibalism. It is known that cannibalistic behaviour varies
      strongly between hybrids and between individuals of the same hybrid. The aim of
      this study was to test specific hypotheses about the causation of cannibalism by
      comparing matched individuals varying in their cannibalistic behaviour. 2. To
      investigate feed efficiency, egg production and feed consumption, data were
      collected over 30 d. Nutrient deficiencies have been associated with outbreaks of
      cannibalism and we hypothesised that cannibals are more feed efficient than their
      flock mates and, therefore, more susceptible to transient nutrient deficiencies
      or imbalances that trigger cannibalistic behaviour. 3. Video recordings were made
      of victims of cloacal cannibalism and their matched controls during oviposition.
      Victims were expected to have longer oviposition durations and a higher incidence
      of short-term cloacal prolapses than controls, because the starting point for
      cannibalism is often suggested to be pecking at the red mucosa of the victim
      during, or just after, oviposition. 4. Oviduct swab samples were taken from
      surviving victims of cloacal cannibalism and their matched controls 4 weeks after
      the cannibalistic attack. If peck wounds provide a route for subsequent bacterial
      invasion of the reproductive tract, victims would be expected to have greater
      bacterial colonisation of the oviduct. 5. Mortality within each matched trio was
      recorded over a 23-month period after the cannibalistic attack. Victims that
      survived a cannibalistic attack were expected to have reduced longevity compared
      to controls and cannibals. This could occur if they developed secondary
      infections as a result of the cannibalistic attack, or if they had poorer health
      even before the attack. 6. No significant differences were found between
      cannibals, victims and controls in feed efficiency or any of the production
      variables measured. Victims of cloacal cannibalism did not expose their cloacal
      mucosa more, or for longer, than matched control hens during oviposition, and had
      no more bacteria in their oviduct. Victims tended to die sooner than their
      matched cannibals or cannibals during a 23-month period after a cannibalistic
      attack.

PMID- 15484719
TI  - Comparative assessment of bone among wild-type, restricted ovulator and out-of
      production hens.
AB  - 1. The aim of this study was to assess bone characteristics in restricted
      ovulator (RO) hens. These hens generally are unable to ovulate due to a point
      mutation in the oocyte VLDL receptor gene whose protein product mediates the
      uptake of yolk precursors. Because these hens do not have the cyclic calcium (Ca)
      metabolism associated with egg formation, they could be a useful model for
      studying bone metabolism. 2. RO hens had greater humerus, femur and tibia ash
      concentrations than wild-type (WT) and out-of-production (OP) hens. Bone mineral
      content and density obtained with dual-energy X-ray absorptiometry (DXA) were
      highly correlated with the results of conventional bone assays. 3. Gross and
      histological examination of the femurs confirmed the presence of extremely dense
      medullary bone deposition in the RO hens. However, the composition of non
      collagenous protein extracts of medullary bone was similar for the two genotypes.
      4. Analysis of medullary bone extracts for glycosaminoglycans (GAG) confirmed the
      presence of large amounts of keratan sulphate (KS) in the matrix of medullary
      bone. 5. Plasma Ca, total GAG and KS concentrations of RO hens were markedly
      higher than WT and OP hens. The changes in plasma calcium and keratan sulphate
      are probably a reflection of elevated Ca-binding yolk precursor molecules and
      intensive medullary bone formation in response to increased plasma oestrogen
      observed by others in RO hens.

PMID- 15484720
TI  - Hatching success and embryonic mortality on lesser rhea (Pterocnemia pennata)
      farms in northern Patagonia, Argentina.
AB  - 1. The hatching success and embryonic mortality of 724 lesser rhea eggs from 12
      farms in northern Patagonia, Argentina were monitored during the 2000 breeding
      season. 2. Average infertility was 24.5%, embryonic mortality was 33.5%,
      hatchability of fertile eggs was 66.5% and the neonatal mortality was 57.0%.
      There were large variations between different farms. 3. Bacterial contamination
      was high and egg hatchability was also affected by the occurrence of oedematous
      and malformed embryos. 4. No significant relationships were found between
      embryonic loss, duration of egg storage, initial egg weight or weight loss of
      hatched and failed eggs. 5. The low productivity on lesser rhea farms is caused
      not only by embryonic mortality but also by a high incidence of infertile eggs
      and neonatal mortality. 6. Bacterial infection may not have been the most
      important cause of incubation failure, indicating that nutritional deficiencies
      and inbreeding may play an important role in the productivity of these farms.

PMID- 15484721
TI  - New approach of testing the effect of heat stress on eggshell quality: mechanical
      and material properties of eggshell and membrane.
AB  - 1. The effect of high temperature on eggshell quality was investigated by
      measuring the mechanical and material properties of shell and membranes. 2. Heat
      exposure resulted in a decrease in zootechnical performance and eggshell
      thickness, increase in egg breakage, and unchanged egg shape index. 3. The static
      stiffness (Kstat), dynamic stiffness (Kdyn) and modulus of elasticity of the
      eggshell were not significantly affected by high temperature. Membrane
      prolongation increased significantly while membrane attachment strength and
      breakage strength tended to decrease and increase, respectively. The
      relationships between these variables were changed by high temperature. 4.
      Neither Kstat nor Kdyn could give a reasonable explanation for the changed
      eggshell quality induced by heat stress. The decreased eggshell thickness and
      changed properties of shell membrane may be responsible, at least partially, for
      the decreased shell quality of eggs from heat-stressed hens.

PMID- 15484722
TI  - Identification of the major proteins of the organic matrix of emu (Dromaius
      novaehollandiae) and rhea (Rhea americana) eggshell calcified layer.
AB  - 1. The eggshell is a composite consisting of 95% calcite and an organic matrix.
      2. While many proteins of the chicken eggshell matrix have already been
      identified, little is known about the matrix of other birds. 3. Isolation of the
      emu and rhea eggshell matrix and analysis of its major constituents showed that
      the predominant components were C-type lectin-like proteins related to those of
      ostrich, chicken and goose. 4. Serum albumin, vitelline membrane outer layer
      protein I (VMO-I) and the turpentine-induced acute phase serum protein 18-B were
      identified as minor components of the emu shell matrix. Both eggshell matrices
      also contained a novel proline- and alanine-rich protein. 5. Like ostrich, and
      unlike chicken and goose, both emu and rhea eggshell matrix contained two
      different C-type lectin-like proteins as major components, indicating that the
      occurrence of two proteins of this family may be widespread among ratites.

PMID- 15484723
TI  - In ovo temperature manipulation influences post-hatch muscle growth in the
      turkey.
AB  - 1. The effect of manipulating egg incubation temperature for short periods on
      turkey muscle development was determined using the M. semitendinosus, a thigh
      muscle, as the model. 2. Experiment 1. Eggs were incubated at a control
      temperature of 37.5 degrees C. For a 4-d period of 0 to 4, 5 to 8, 9 to 12, 13 to
      16, 17 to 20 or 21 to 24 embryonic days (ED) eggs were transferred to either 38.5
      or 35.5 degrees C. A regime of 38.5 degrees C at 5 to 8 and 9 to 12 ED caused an
      increased myonuclei number and muscle fibre number, respectively. 3. Experiment
      2. Eggs were incubated at a control temperature of 37.5 degrees C. At 5 to 8 ED
      eggs were transferred to 38.5 or 35.5 degrees C. Temperature-manipulated embryos
      showed a delay in differentiation (myogenin expression) of the semitendinosus
      muscle compared to controls. 4. Manipulating the incubation temperature for 4 d
      in early incubation alters muscle development in the turkey with no observation
      of deformities or reduction in hatchability. We speculate that this increase in
      temperature may result in an improved muscle growth in the post-hatch bird.

PMID- 15484724
TI  - Effects of supplementary iodine on the performance and egg traits of laying hens.
AB  - 1. This experiment was carried out to determine the effects of dietary iodine
      supplementation on the performance and egg traits of laying hens. A total of 600
      SHSY type brown layers aged 21 weeks of age were chosen at random from a large
      flock. They were randomly distributed into 30 pens at 20 hens per pen. Each
      treatment comprised 6 replicates of 20 layers in groups of 5 birds. The diets
      were supplemented with 0, 3, 6, 12 and 24 mg/kg iodine as calcium iodate. The
      experimental period lasted 30 weeks. 2. There were no significant differences
      among the groups in body weight, food consumption, egg production, food
      consumption per kg eggs, eggshell index, eggshell breaking strength, shell
      thickness or egg yolk index. 3. Supplementation of the diet with 12 mg/kg iodine
      increased food consumption per dozen eggs compared to the groups fed on diets
      supplemented with 0 and 6 mg/kg iodine. 4. Egg weight was less in groups fed on
      diets supplemented with 12 and 24 mg/kg iodine than in the group receiving no
      iodine supplementation. 5. Iodine supplementation to provide 12 and 24 mg/kg
      reduced egg albumen index and egg Haugh units. 6. There were no significant
      differences among the groups in egg cholesterol and egg yolk cholesterol
      contents. 7. The iodine concentrations in egg yolk, egg albumen and whole egg
      increased with increased iodine supplementation. 8. As a result, the 3 and 6
      mg/kg iodine supplementation of diet could be used to enrich the eggs with iodine
      without any adverse effect on performance and egg traits.

PMID- 15484725
TI  - Effect of different dietary ideal protein concentrations on broiler performance.
AB  - 1. The aim of the study was to examine the response of male broilers of different
      age categories to different dietary ideal protein (IP) concentrations and to
      compare the effects to IP recommendations based on single lysine (Lys)
      requirement studies from the literature. 2. Two experiments were carried out, in
      which diets containing different IP concentrations (9.0 to 14.4g apparent faecal
      digestible (AFD) Lys/kg) were fed to male broilers from 14 to 34 (Exp. 1) and 28
      to 41 d of age (Exp. 2). The diets (12.88MJ AMEN/kg) were prepared by the
      dilution technique. The effect of dietary IP concentrations on weight gain, feed
      intake, feed conversion efficiency (FCE) and slaughter characteristics were
      studied in both experiments. 3. In Exp. 1, weight gain and FCE increased linearly
      and fat concentration in the carcase decreased with increasing IP concentration.
      In Exp. 2, weight gain and FCE improved exponentially, whereas breast meat yield
      improved linearly with increasing dietary IP concentration. On the basis of these
      results, it was concluded that the weight gain and FCE of male broilers respond
      to higher dietary IP levels than would be expected from single lysine requirement
      studies in the literature.

PMID- 15484726
TI  - Effect of graded levels of aflatoxin, ochratoxin and their combinations on the
      performance and immune response of broilers.
AB  - 1. The effects of dietary aflatoxin (AF, 0.5, 1.0 and 2.0 mg/kg), ochratoxin (OA,
      1.0, 2.0 and 4.0 mg/kg) or combinations of these on body weight gain, feed
      efficiency, organ weights and immune response were studied in broilers. 2.
      Significant growth depression, reduced food consumption and poor food conversion
      efficiency were recorded in broilers fed a diet containing the greater
      concentrations of AF (1 and 2 mg/kg) and OA (2 and 4 mg/kg). 3. The combination
      of 2 mg/kg AF and 4 mg/kg OA exerted the maximum adverse effect on growth, feed
      intake and feed efficiency, indicating a synergistic effect on performance. 4. AF
      at 2 mg/kg in the diet caused a significant increase in the relative weight of
      liver, whereas the relative weight of kidney was significantly increased at 4
      mg/kg of OA. A significant decrease in the relative weight of the bursa of
      Fabricius was noted at the highest concentration of AF (2 mg/kg) and combinations
      of 1 and 2 mg/kg AF and 2 and 4 mg/kg OA. 5. Cell mediated immunity (CMI), in
      terms of mean skin thickness (MST) sensitive to dinitrochlorobenzene (DNCB), was
      significantly reduced in chicks given the combination of 2 mg/kg AF and 4 mg/kg
      OA. Haemagglutination (HA) titre against sheep red blood cells (SRBCs) peaked at
      42 d of age. At 42 and 47 d of age, a significant decrease in HA titres was
      recorded in chicks given 4 mg/kg OA or a combination of AF (1 or 2 mg/kg) and OA
      (2 or 4 mg/kg). 6. AF at a dietary concentration of 1 mg/kg or more and OA at 2
      mg/kg or more, either alone or in combination, caused severe reductions in growth
      and immune response.

PMID- 15484727
TI  - Food intake, growth rate, food conversion and food choice in broilers fed on
      diets high in rapeseed meal and pea meal, with observations on sensory evaluation
      of the resulting poultry meat.
AB  - 1. Experiments were done to measure the effects of 100 and 200 g/kg of either pea
      meal or low glucosinolate, low erucic acid rapeseed meal on food intake and
      growth, food choice and meat organoleptic quality in broiler chickens. 2. The
      test diets were formulated to be iso-energetic and iso-nitrogenous with a soy
      wheat control diet. In all diets, lysine was fixed at 11.0 g/kg and all other
      indispensable amino acids were present in excess of requirements. 3. Food intake
      was little affected by the inclusion of 100 g/kg of pea meal in the diet but 200
      g/kg of peas caused a decrease. Rapeseed produced a decrease in food intake at
      both dietary concentrations. 4. Weight gain was similarly affected, but food
      conversion from d 0 to d 42 was little affected by the inclusion of either peas
      or rapeseed. 5. Absolute breast muscle weight was affected by diet but there was
      no significant difference in breast weight as a proportion of total body weight.
      6. From d 7 onwards, selection against the pea-containing diet approached
      statistical significance. Between d 7 and d 14, birds ate almost twice as much of
      the control as of the pea-containing diet. Birds offered a rapeseed meal diet ate
      similar amounts of that and the control diet. 7. The breast meat from birds given
      200 g rapeseed/kg was the only meat identified as different but no strong
      aversion was expressed by the tasting panel.

PMID- 15484728
TI  - Effects of dietary conjugated linoleic acid and fish oil supplementation on
      performance and egg quality in laying hens.
AB  - 1. Laying hen performance, yolk fat fatty acid concentrations and firmness of
      eggs were evaluated with respect to the inclusion in the diet of conjugated
      linoleic acid (CLA) and fish oil. 2. Nine diets were arranged factorially, with
      three levels of supplementation of CLA (1, 3 and 5 g/kg) and fish oil (0, 14 and
      20 g/kg). 3. Type of diet did not affect egg production traits. 4. CLA addition
      increased yolk weight and yolk fat concentrations of CLA, saturated and total
      long-chain n-3 fatty acids, but decreased those of monounsaturated and total long
      chain n-6 fatty acids. 5. Fish oil addition increased long-chain n-3 fatty acids
      yolk fat concentrations but decreased those of CLA, saturated and long-chain n-6
      fatty acids. 6. Effects of CLA addition on yolk fat concentrations of C22:4 n-6
      and C20:5 n-3 were greater when no fish oil was added to the diet. 7. CLA
      supplementation increased linearly yolk moisture and firmness and altered albumen
      and yolk pH.

PMID- 15484729
TI  - Effects of dietary copper on production and egg cholesterol content in laying
      hens.
AB  - 1. This experiment was carried out to determine the effects of diets supplemented
      with different amounts of copper on egg production, food intake, food conversion
      ratio, egg weight, damaged egg ratio, specific gravity, mortality and cholesterol
      concentration in yolk. The experiment lasted 90 d and 400 Hisex-Brown hens, aged
      27 weeks at the start of the study, were used. 2. There were no statistically
      significant effects of supplementary copper on egg production, food intake or
      food conversion efficiency. 3. There were no statistically significant
      differences between the groups in terms of damaged eggs, egg weight, specific
      gravity and live weight. 4. At the end of the experiment, the lowest yolk
      cholesterol concentrations were obtained in the 150 kg/kg copper group and the
      greatest concentrations were in the control group. 5. Consequently, the use of
      supplementary copper to provide 150 kg/kg in poultry diets was concluded to
      decrease yolk cholesterol concentrations without any effect on production
      performance.

PMID- 15484730
TI  - Effects of supplemental copper and chromium on the serum and egg traits of laying
      hens.
AB  - 1. This study investigated the effects of supplemental copper and chromium on the
      serum and egg traits of laying hens using 144 forty-five-week-old White Leghorn
      layers. The hens were randomly assigned into 9 groups to conduct this 3 copper
      (0, 125 and 250 mg/kg as copper sulphate) x 3 chromium (0, 800 and 1600 microg/kg
      as chromium picolinate) factorial trial. 2. Egg yolk cholesterol was
      significantly reduced by supplementary copper (Cu) and chromium (Cr) and there
      was an interaction between Cu and Cr supplementation. Egg production, egg weight,
      eggshell strength and eggshell thickness were not influenced by Cu or Cr
      supplementation. 3. Serum cholesterol concentration was decreased by Cu
      supplementation and very low-density lipoprotein (VLDL) was reduced markedly by
      both Cu and Cr. On the other hand, high-density lipoprotein (HDL) was
      significantly increased by Cu and Cr. Interaction occurred between Cu and Cr in
      the VLDL and HDL parameters. Supplmentary Cu also reduced VLDL-cholesterol (VLDL
      C) and enhanced HDL-cholesterol (HDL-C), while supplemental Cr had a contrary
      effect on these two parameters. 4. If minimum egg cholesterol content is the
      criterion, this study suggests that 125 mg/kg of Cu together with 800 to 1600
      microg/kg of Cr provide adequate supplementary concentrations for laying hens.

PMID- 15484731
TI  - Distribution and depletion of flubendazole and its metabolites in edible tissues
      of guinea fowl.
AB  - 1. We measured the distribution and depletion of residues of flubendazole and its
      major metabolites in breast muscle, thigh muscle and liver of guinea fowls during
      and after oral administration of the veterinary medicine Flubenol 5% at two
      doses. 2. The guinea fowls were treated orally with normal feed, medicated at
      doses of 56 and 86 mg per kg feed for 7 successive days. Afterwards, depletion
      was observed for 8 d. Just before slaughter, body weights were measured. Thigh
      muscle, breast muscle and liver of three female and three male birds were
      sampled. The concentrations of the flubendazole-derived residues were determined
      by a liquid chromatographic-mass spectrometric method. 3. The highest residue
      concentrations were obtained for the reduced metabolite. With the therapeutic
      dose, the maximum mean residue concentrations obtained for this compound in thigh
      muscle, breast muscle and liver were 312, 288 and 1043 microg/kg, respectively.
      The values for flubendazole, the parent molecule, were 114, 108 and 108
      microg/kg, respectively. The residues of the hydrolysed metabolite were
      negligible in the sampled muscle tissues. After 24 h of depletion, the sum of the
      residues of parent and metabolites in muscle tissue still exceeded 50 microg/kg.
      After 8 d of depletion, flubendazole-derived residues at low concentrations could
      still be measured in both muscle tissues and liver. Generally, the disposition of
      residues in breast and thigh muscle was comparable. 4. The European Union has not
      established a maximum residue limit (MRL) for flubendazole in edible tissues of
      guinea fowl. In contrast, the existing MRLs for other bird species are expressed
      as the sum of parent flubendazole and its hydrolysed metabolites. An estimated
      withdrawal period of three days will assure residue safety in the edible tissues
      of guinea fowl treated with flubendazole at therapeutic dose. After this
      withdrawal period following treatment of the guinea fowl, the residues were
      approximately constant, very low and far below the established safe MRL level for
      other bird species.

PMID- 15484732
TI  - Disposition kinetics of doxycycline in chickens naturally infected with
      Mycoplasma gallisepticum.
AB  - 1. The pharmacokinetic properties of doxycycline were determined in healthy
      chickens and chickens naturally infected with Mycoplasma gallisepticum after a
      single intravenous (i.v.) and oral administration of the drug at 20 mg/kg body
      weight. Tissue residues of the tested drug after an oral dose of 20 mg/kg given
      twice daily for 5 consecutive days were also estimated in diseased chickens. 2.
      The plasma concentrations of doxycycline following single i.v. and oral
      administration were higher in healthy chickens than in diseased ones. Following
      i.v. injection, the elimination half-life (t1/2beta), distribution half-life and
      mean residence time (MRT) were longer in healthy chickens than in diseased birds.
      The values of total body clearance (ClB) and volume of distribution (Vdss) were
      larger in healthy chickens than in diseased birds. 3. After single oral
      administration, the absorption half-life (tl/2ab) and the elimination half-life
      were longer in normal birds than in diseased ones. The maximum plasma
      concentration of the drug was higher in normal chickens than in diseased ones. 4.
      Following repeated oral administration, the concentration of doxycycline in all
      tissues except muscle was higher than the corresponding concentrations in plasma.
      Concentrations of doxycycline in different tissues were in the following order:
      kidney > liver > lung > muscle. The drug was detected in liver and kidney in
      substantial concentrations on d 5 post administration of the last dose whereas,
      on d 7, its concentration in all tissues was below the lower limit of the
      sensitivity of the assay method used. Because of the low sensitivity of the
      microbiological assay method used in this study, a safe withdrawal time for
      doxycycline in diseased birds could not be estimated for the meanwhile.

PMID- 15484733
TI  - Constant photoperiods and sexual maturity in broiler breeder pullets.
AB  - 1. Broiler breeder pullets were maintained on 10-, 11-, 12-, 13-, 14- or 16-h
      photoperiods to determine the effect of constant photoperiods on sexual
      development in broiler breeders. The birds were fed to achieve a 2100 g body
      weight at approximately 17 or 20 weeks to see if the photosexual response was
      modified by rate of growth. 2. In both body weight groups, pullets maintained on
      10h were the first to reach sexual maturity (50 eggs/100 bird-d), and these and
      the 11-h pullets matured significantly earlier than any of the other photoperiod
      groups. Pullets maintained on 13 or 14 h matured latest, at about 3 weeks after
      the 10-h pullets, though both were only marginally later than the 12- or 16-h
      birds. These differences in maturation probably reflect the different rates at
      which photorefractoriness is dissipated in broiler breeders reared on
      photoperiods that vary in their degree of stimulatory competence. 3. There were
      no significant interactions among the photoperiods and the ages at 2100 g; faster
      growing birds consistently matured about 10 d earlier than conventionally grown
      pullets.

PMID- 15484734
TI  - Photoperiod and oviposition time in broiler breeders.
AB  - 1. Oviposition times were recorded for broiler breeder hens under 8-, 10-, 11-,
      12-, 13-, 14- and 16-h photoperiods. 2. Mean oviposition time (MOT) was delayed
      relative to dawn by approximately 0.5 h for each 1-h increase in photoperiod up
      to 14 h, but was similar for 14- and 16-h photoperiods. However, the 0.5 h/h
      regression for the time when half the eggs were laid continued through to 16 h.
      3. The rate of change in MOT for each 1-h increase in < or = 14-h photoperiod was
      similar to that reported for early and modern egg-type hybrids, but, compared
      with modern genotypes, time of lay itself was 1 h later than white-egg and 2.5 h
      later than brown-egg hybrids. 4. At photoperiods < or = 12.25 h, the number of
      eggs laid before dawn increased by 4-5% for each 1-h reduction in daylength.

PMID- 15484735
TI  - Plasma chemistry reference values from captive red-legged partridges (Alectoris
      rufa).
AB  - 1. Haematological and plasma biochemical parameters of 66 captive red-legged
      partridges (Alectoris rufa) of both sexes were analysed in order to determine
      reference values, taking sex and age into account. 2. There were no statistically
      significant differences in haematocrit, plasma glucose content or creatine kinase
      activity either with age or between sexes. 3. Plasma cholesterol concentrations
      showed differences between sexes, whereas the plasma concentrations of urea, uric
      acid and creatinine were significantly affected by age. 4. Plasma triglyceride
      and total protein concentrations were affected by both sex and age. 5. A peak at
      6 months old in those parameters related to protein metabolism, such as urea,
      uric acid and creatinine may be related to the end of the growing period and the
      start of ovulation after moulting.

PMID- 15484736
TI  - Odour management tools--filling the gaps.
AB  - In many countries the approach to odour management and regulation is increasingly
      based on quantitative techniques and criteria for acceptable exposure to odours
      in the living environment. A range of tools exists for implementing this
      approach, from emission measurement to assessment of effects. Some of these tools
      are well developed and validated, such as the use of olfactometry in laboratories
      operating according to international standards (EN13725:2003) and applying
      quality control and assessment systems under strict supervision by accreditation
      bodies. But other tools, while widely used, which are really still in the
      development stage, without standardisation or adequate validation. And then there
      are those that are still on the "wish list" of methods we would like to have in
      our toolbox. This paper contains a gap analysis that aims to provoke discussion
      on the needs for concerted R&D, standardisation and validation.

PMID- 15484737
TI  - Water Environment Research Foundation (WERF) anaerobic digestion and related
      processes, odour and health effects study.
AB  - Biosolids odour emissions can affect the ability of wastewater utilities to
      implement beneficial biosolids processing and reuse programs. Communities often
      become more sensitised and vocal about biosolids issues, once they experience
      odours emanating from a nearby site. Odour impacts from biosolids, including
      potential human health effects, have been targeted recently by many national and
      local newspapers, citizens' groups, and regulatory agencies, who have raised
      significant concerns, ranging from viable disposal methods/sites to outright
      bans. Many national and local regulatory agencies in the United States are
      considering biosolids disposal bans in their communities because of
      misinformation, poor science, and citizen pressure, but primarily because of
      odour impact concerns. The wastewater industry has a relatively poor
      understanding of the operations and treatment parameters that influence biosolids
      odour emissions. Thus, wastewater treatment plants are often unable to control
      the odour quality of the biosolids that are delivered into communities. A
      research study to demonstrate the influence of anaerobic digestion, mechanical
      dewatering, and storage design and operating parameters on the odour quality of
      the final product was performed and is the subject of this paper. Established and
      new sampling and analytical methods were used to measure biosolids odour
      emissions from 11 test sites in North America. By determining the impacts of
      these control variables on biosolids odour quality, design and operations of
      anaerobic digestion systems might be enhanced. This paper also summarises a
      corollary study performed as part of the WERF research study that addresses the
      health effects of biosolids odours.

PMID- 15484738
TI  - Odour management plans: a risk-based approach using stakeholder data.
AB  - Annoyance is a familiar reaction to odours arising from wastewater treatment
      sites, a reaction which can result in complaints and prosecutions. Odour
      management plans can be used to assess the extent of nuisance caused and
      prioritise mitigation measures. Often, these plans have been developed purely on
      the basis of technical assessments of emission and dispersion, with the general
      aim of limiting odour concentrations to a specific threshold at some distance
      from the works. They have often been prepared with inconsistent communication
      between the site staff and consultant during the development process, and may not
      directly refer to the affected population. This paper describes a risk-based
      approach to developing odour management plans, in which mitigation measures are
      assessed and prioritised on the basis of the likely frequency and intensity of
      odour exposure. A key element of the approach is the use of knowledge from data
      gained from key stakeholder groups: customers, staff, and regulators. Emphasis is
      placed on the development of clear communications between these groups, which
      helps both in terms of raising awareness amongst operators as to the significance
      of odour problems, and also in managing the expectations of customers and
      regulators. The practical application of this approach is demonstrated by the
      development of odour management plans for wastewater treatment sites by Yorkshire
      Water Services Ltd. These have used data from staff, customers and regulators to
      develop risk grids, which are then used to prioritise remediation measures.
      Involving staff in the data collection operations has been successful in raising
      awareness of the significance of odours, and has in turn led to low-cost emission
      reductions through improved housekeeping. Improved communications between
      operators, customers and regulators has led to more realistic expectations with
      regard to odour problems, a situation which can reduce conflict and prevent the
      imposition of stringent and sometimes unrealistic odour standards.

PMID- 15484739
TI  - The value of an odor-quality-wheel classification scheme for wastewater treatment
      plants.
AB  - Each odorant possesses a unique odor signature (i.e. odor character or quality,
      odor threshold and chemical concentration). This paper develops an initial
      understanding of how the volatile odorous chemicals and their relative
      concentrations produced are related to the total odor quality from the process by
      their odor threshold concentrations and odor signatures.

PMID- 15484740
TI  - Ecological assessment of waste air treatment systems in the case of biological
      waste treatment.
AB  - In this paper, the authors present a technique aimed at increasing the efficiency
      of biological waste air treatment. The objective is to modify the existing
      biological waste air treatment systems (i.e. biofilters) to reduce the emitted
      substances and their potential environmental impacts. The principle of the
      ionization system is described, along with the first experiences of applying
      those methods during the rotting process. The investigated system is evaluated by
      means of life cycle impact assessment, with a focus on odour. It is demonstrated
      which of the measured substances (i.e. VOC) can potentially contribute to the
      odorant concentration. Further, it is shown which odour-intensive substances can
      be reduced by deploying ionization. Finally, the authors respond to the fact that
      the cleaning efficiency of ionization strongly depends on the humidity of the
      treated waste gas stream.

PMID- 15484741
TI  - Identification of the odour and chemical composition of alumina refinery air
      emissions.
AB  - Alcoa World Alumina Australia has undertaken comprehensive air emissions
      monitoring aimed at characterising and quantifying the complete range of
      emissions to the atmosphere from Bayer refining of alumina at its Western
      Australian refineries. To the best of our knowledge, this project represents the
      most complete air emissions inventory of a Bayer refinery conducted in the
      worldwide alumina industry. It adds considerably to knowledge of air emission
      factors available for use in emissions estimation required under national
      pollutant release and transfer registers (NPRTs), such as the Toxic Releases
      Inventory, USA, and the National Pollutant Inventory, Australia. It also allows
      the preliminary identification of the key chemical components responsible for
      characteristic alumina refinery odours and the contribution of these components
      to the quality, or hedonic tone, of the odours. The strength and acceptability of
      refinery odours to employees and neighbours appears to be dependent upon where
      and in what proportion the odorous gases have been emitted from the refineries.
      This paper presents the results of the programme and develops a basis for
      classifying the odour properties of the key emission sources in the alumina
      refining process.

PMID- 15484742
TI  - Evaluation of a novel wind tunnel for the measurement of the kinetics of odour
      emissions from piggery effluent.
AB  - A novel laboratory wind tunnel, with the capability to control factors such as
      air flow-rate, was developed to measure the kinetics of odour emissions from
      liquid effluent. The tunnel allows the emission of odours and other volatiles
      under an atmospheric transport system similar to ambient conditions. Sensors for
      wind speed, temperature and humidity were installed and calibrated. To calibrate
      the wind tunnel, trials were performed to determine the gas recovery efficiency
      under different air flow-rates (ranging from 0.001 to 0.028m3/s) and gas supply
      rates (ranging from 2.5 to 10.0 L/min) using a standard CO gas mixture. The
      results have shown gas recovery efficiencies ranging from 61.7 to 106.8%, while
      the average result from the trials was 81.14%. From statistical analysis, it was
      observed that the highest, most reliable gas recovery efficiency of the tunnel
      was 88.9%. The values of air flow-rate and gas supply rate corresponding to the
      highest gas recovery efficiency were 0.028 m3/s and 10.0 L/min respectively. This
      study suggested that the wind tunnel would provide precise estimates of odour
      emission rate. However, the wind tunnel needs to be calibrated to compensate for
      errors caused by different air flow-rates.

PMID- 15484743
TI  - Aerodynamic performance of a low-speed wind tunnel.
AB  - The determination of the odour mass flow emitted from a source is a very
      important step and forms the basis for all subsequent considerations and
      calculations. Wastewater treatment plants, as well as waste treatment facilities,
      consist of different kinds of odour sources. Unfortunately, most of the sources
      are passive sources, where no outward air flow-rate can be measured, but where
      odorants are obviously emitted. Thus, a type of sampling is required that allows
      to measure the emitted odour flow-rate (OFR). To achieve this, different methods
      are in use worldwide. Besides indirect methods, such as micrometeorological
      atmospheric dispersion models, which have not been used in Germany (in other
      countries due to different problems, direct methods are also used). Direct
      measurements include hood methods, commonly divided into static flux chambers,
      dynamic flux chambers and wind tunnels. The wind tunnel that we have been
      operating in principle since 1983 is different from all subsequent presented wind
      tunnels, in that we operate it at a considerably lower wind speed than the
      others. To describe the behaviour of this wind tunnel, measurement of the flow
      pattern in this low-speed tunnel are under way, and some initial results are
      presented here.

PMID- 15484744
TI  - Variability and repeatability of olfactometric results of n-butanol, pig odour
      and a synthetic gas mixture.
AB  - For the purposes of a research project for the Flemish authorities, olfactometric
      measurements were carried out at six closed pig farms and six fattener farms. The
      results of these olfactometric measurements were compared with the olfactometric
      results of n-butanol samples and samples of a synthetic gas mixture of
      ethanethiol, methylacetate and 2-propanol in nitrogen, both analysed on the same
      days as the air samples from the pig farms. The results of the n-butanol tests
      for all panellists showed that nobody was qualified according to the CEN
      criteria, and that, consequently, these criteria are rather stringent. Comparing
      the variability of the results for the three different odours showed that the
      mean and standard deviation of the mean variance were not significantly different
      for the three odour types, which means that the repeatability of the panellist
      results was equal for the examined odour types. The principle of traceability was
      checked by comparing the variance of the n-butanol, pig odour and synthetic
      mixture ratio. For the complete dataset, the principle of traceability could not
      been proven for n-butanol. For the restricted dataset, the principle of
      traceability was more valid for n-butanol than for the mixture, but differences
      were small. Finally, normalization was looked for with regard to olfactometric
      measurements of air samples from pig arms based either on n-butanol or on the
      synthetic mixture. Both models had low determination coefficients, but the model
      based on the synthetic mixture gave better results than the one based on n
      butanol.

PMID- 15484745
TI  - Comparison of field olfactometers in a controlled chamber using hydrogen sulfide
      as the test odorant.
AB  - A standard method for measuring and quantifying odour in the ambient air utilizes
      a portable odour detecting and measuring device known as a field olfactometer (US
      Public Health Service Project Grant A-58-541). The field olfactometer dynamically
      dilutes the ambient air with carbon-filtered air in distinct ratios known as
      "Dilutions-to-Threshold" dilution factors (D/Ts), i.e. 2, 4, 7, 15, etc. Thirteen
      US states and several cities in North America currently utilize field
      olfactometry as a key component of determining compliance to odour regulations
      and ordinances. A controlled environmental chamber was utilized, with hydrogen
      sulfide as the known test odorant. A hydrogen sulfide environment was created in
      this controlled chamber using an Advanced Calibration Designs, Inc. Cal2000
      Hydrogen Sulfide Generator. The hydrogen sulfide concentration inside the chamber
      was monitored using an Arizona Instruments, Inc. Jerome Model 631 H2S Analyzer.
      When the environmental chamber reached a desired test concentration, test
      operators entered the chamber. The dilution-to-threshold odour concentration was
      measured using a Nasal Ranger Field Olfactometer (St Croix Sensory, Inc.) and a
      Barnebey Sutcliffe Corp. Scentometer. The actual hydrogen sulfide concentration
      was also measured at the location in the room where the operators were standing
      while using the two types of field olfactometers. This paper presents a
      correlation between dilution-to-threshold values (D/T) and hydrogen sulfide
      ambient concentration. For example, a D/T of 7 corresponds to ambient H2S
      concentrations of 5.7-15.6 microg/m3 (4-11 ppbv). During this study, no
      significant difference was found between results obtained using the Scentometer
      or the Nasal Ranger (r = 0.82). Also, no significant difference was found between
      results of multiple Nasal Ranger users (p = 0.309). The field olfactometers
      yielded hydrogen sulfide thresholds of 0.7-3.0 microg/m3 (0.5-2.0 ppbv).
      Laboratory olfactometry yielded comparable thresholds of 0.64-1.3 microg/m3 (0.45
      0.9 ppbv). These thresholds are consistent with published values.

PMID- 15484746
TI  - Odour intensity and hedonic tone--important parameters to describe odour
      annoyance to residents?
AB  - The Guideline on Odour in Ambient Air has been in use for many years for odour
      regulation in Germany. The main parameter that the odour regulation authority has
      to take into account is the odour frequency expressed as odour hours per year. In
      the guideline, limit values are given for the maximum odour frequency per year.
      These limit values are based on field investigations in which significant
      relationships between odour impact and odour annoyance was found. In these
      investigations, odour intensity did not yield a better description of the degree
      of annoyance caused to the residents. The hedonic tone was not mentioned. In a
      new research project finished in 2003, the influence of odour intensity and
      hedonic tone, in addition to odour frequency, has been assessed. Two
      installations emitting pleasant odours, two emitting neutral and two emitting
      unpleasant odours, have been selected. In each case grid field measurements by a
      panel were carried out, and the annoyance of the residents was assessed using a
      special questionnaire. The results of this project are: (1) A new method to
      measure odour intensity and hedonic tone in the field with data record forms was
      developed and validated. With this method, reliable and reproducible results are
      obtained. (2) The parameter odour frequency based on the system of "odour hours"
      is suitable and sufficient to predict the odour annoyance caused by
      unpleasant/neutral odours. (3) In the case of pleasant odours, hedonic tone has
      an abundantly clear effect on the dose-response relationship between odour
      frequency and annoyance. Pleasant odours have a significant lower annoyance
      potential than unpleasant/neutral odours. (4) The odour intensity has no
      additional influence on this relationship. If odours are recognisable then they
      can cause annoyance.

PMID- 15484747
TI  - Monitoring of biological odour filtration in closed environments with
      olfactometry and an electronic nose.
AB  - Air treatment with a compact biological membrane filter, and air quality
      monitoring with an electronic nose were tested in the laboratory on air from a
      cage containing six mice. Additional analyses of air to and from the filter were
      performed using olfactometry and ammonia and hydrogen sulphide gas detection
      tubes. The biological air filter is a module containing biofilm-coated membrane
      fibres that separate a closed liquid loop from a gas phase. Odour compounds and
      oxygen diffuse through the membranes from the gas phase to the biofilm, where
      they are degraded to carbon dioxide and water. The prototype "ENQBE" electronic
      nose is based on an array of eight thickness shear mode resonators (TSMR), also
      known in the literature as quartz microbalance sensors. The chemical sensitivity
      is given by molecular films of metalloporphyrins and similar compounds. Chemical
      interaction of compounds in the air with the vibrating sensors induces a
      frequency change of the vibration that can be measured as a signal. The air from
      the mouse cage had a strong odour (3490 OUE/m3). The biological membrane filter
      performed well, achieving over 80% odour and ammonia reduction. The electronic
      nose signal could be correlated with the inlet and outlet air-quality of the
      biological filter, making it a promising method for monitoring air quality in
      closed environments.

PMID- 15484748
TI  - Determination of the dynamics of the odour release from a pig house, using an
      electronic odour sensor.
AB  - The widely fluctuating operating conditions in pig husbandry, due to climatic and
      biological changes (changes in temperature and air flowrate between day and
      night, as well as between summer and winter, increasing animal mass during the
      fattening process, etc.) exert a significant influence on the amount of actual
      odour emission. The project presented here comprised the measurement of seasonal
      (fattening course), daytime-related, and short-term (feeding) dynamic effects of
      odour release, as well as the identification of potential factors which influence
      the amount of odour emitted. In parallel with "classic" olfactometry, an
      electronic odour sensor with a chemosensor array of ten metal oxide sensors was
      employed. The highest odour emissions are measured on hot summer days, while the
      lowest emissions were determined on cold winter days. On the one hand, the sensor
      signals of the electronic odour sensor exhibited considerable differences on days
      with large volume flow alterations. On the other hand, continuous measurement
      with the electronic odour sensor allowed changes in the gas- and odorant
      composition of the exhaust air during feeding times to be shown. From the
      measurement results, recommendations for odour sampling, the consideration of
      seasonal odour emission fluctuations, and the use of electronic odour sensors for
      the evaluation of odour emissions have been derived.

PMID- 15484749
TI  - Ambient odour testing of concentrated animal feeding operations using field and
      laboratory olfactometers.
AB  - The Missouri Air Conservation Commission regulations include regulations that
      limit the amount of acceptable odor from confined animal feeding operations
      (CAFOs). The regulations concerning odor designate the use of a scentometer as a
      screening tool. The rules dictate that if an odor is detectable by an
      investigator at a dilution ratio of 5.4 using a scentometer then an air sample
      should be collected and sent to an olfactometry laboratory for an odor panel to
      determine the detection threshold and the intensity of the odor sample. The
      detection thresholds are determined following ASTM E679-91 and EN13725. The
      intensity is determined following ASTM E544-99. If the olfactometry laboratory
      determined the detection threshold of the sample to be above seven, then the CAFO
      would be in violation. If the olfactometry laboratory determined the intensity
      level to be above a level equivalent to 225 ppm of n-butanol, then the source of
      odor would be in violation. The CAFO odor rules came under scrutiny by
      representatives of the largest hog producer in the State of Missouri.
      Specifically, they argued that the detection threshold limit of seven in the CAFO
      portion of the rule was too low for the rule to realistically identify a
      violation. This paper presents the results of a study to find the appropriate
      regulatory level of odor as determined by laboratory olfactometry. The study took
      place from November 2001 to October 2002. Samples were collected from field
      locations that exhibited odor produced by confined animal feeding operations and
      from areas exhibiting no apparent odor. The odors were categorized based upon the
      scentometer level at which the odors were detectable, and then samples were sent
      to an odor evaluation laboratory for analysis by olfactometry.

PMID- 15484750
TI  - Analysis of sulfur and nitrogen odorants using solid-phase microextraction and GC
      MS.
AB  - An analytical method involving solid-phase micro-extraction (SPME) and gas
      chromatography-mass spectrometry (GC-MS) was applied to analyze biosolids odors.
      A selective ion monitoring (SIM)-based MS method was developed, using SPME
      injections of odorant standards under the full-scan mode to select the
      quantification and confirmation ions for each odorant. The odorants analyzed in
      this study include: dimethylsulfide, dimethyldisulfide, methyl mercaptan,
      hydrogen sulfide, carbon disulfide, trimethylamine and dimethylamine. We have
      used this method to quantify parts-per-billion levels of odorant vapors produced
      during anaerobic incubation of digested wastewater sludge. Important
      considerations for expedient and accurate calibration under static and dynamic
      flow conditions are discussed. The SPME-GC-MS method may give a positive
      intercept in the calibration curve, especially under static sampling conditions,
      which sets a practical detection limit for odor analysis.

PMID- 15484751
TI  - Cryogenic trapping for determination of odor concentration.
AB  - The sensory testing method applied under Japanese law to measure odor
      concentration has a lower detection limit of 10 in the specified Odor Index. To
      measure odor below the limit, a condensing procedure using solid sorbents (Tenax
      TA, Unicarbon B and Carbosieve SIII) has been developed and used in Japan. This
      procedure however cannot condense all odorous substances, and is specifically
      unsuited to hydrogen sulfide, methyl mercaptan, dimethyl sulfide, ammonia, and
      other typical odorous substances. In the present study, cryogenic trapping was
      tested to improve recovery rate. As water in sample air causes choking of the
      trap tube, vacant pre-columns to condense the water were connected to the Tenax
      TA-packed column. The columns were chilled with liquid oxygen before passage of
      100 L of sample air. The columns were then heated to 200 degrees C under passage
      of 50 mL/min of nitrogen carrier gas to desorb odors. The desorbed gases were
      captured in sampling bags made of polyethylene terephthalate film. The total
      volume of desorbed gases was approximately 1 L. The method showed good recovery
      rates for hydrogen sulfide, methyl mercaptan, dimethyl sulfide and ammonia, and
      was useful for determining low-level odor concentrations during measurement of
      odor in ambient air at various sites in Osaka City.

PMID- 15484752
TI  - Effect of back-pressure on absorption efficiency of impingers used for air
      sampling.
AB  - The gas-liquid absorption method, using an impinger as an extracting device, is
      the most common method for quantifying most gaseous pollutants. The performance
      of conventional impingers was studied, and several modified impingers were
      tested. It was found that the sampling efficiency varied from impinger to
      impinger, which resulted from back-pressure differences between impingers. The
      back-pressure of ten tested impingers ranged between 160 mm to 520 mm water gage
      when a 50 mL absorbing solution was used, which caused the ammonia concentration
      coefficients of variations to be up to 15%. It was also verified that an open
      bubble distribution tube could be used to eliminate back-pressure variations
      between impingers. Nearly identical back-pressure (44 +/- 4 mm water gage) could
      be obtained. This modification can improve measurement repeatability
      significantly and reduce the coefficient of variation of measurements to 1.2%.
      With this modification to the impingers, greater accuracy, repeatability and
      comparison of results can be achieved in the measurement of gaseous pollutants in
      air.

PMID- 15484753
TI  - Evaluating odour impacts from a landfilling and composting site: involving
      citizens in the monitoring.
AB  - The City of Montreal operates a large sanitary landfill site within a densely
      populated urban area. Adjacent to the landfill site is a yard waste composting
      facility that processes 10,000 metric tons per year using the windrow technique.
      Over the years, numerous complaints have been received from citizens in the
      surrounding area regarding odours, particularly during the fall period. Aware of
      this nuisance, the City of Montreal wanted to identify odour sources, management
      operations leading to odours, and weather conditions accentuating odours, as well
      as to quantify actual odour impact. Forty-three (43) citizens living adjacent to
      this site were recruited and trained to make odour observations during the fall
      of 2000. This paper presents the methodology used to select and train the
      citizens chosen to make odour observations, to quantify and to identify odours.
      It also presents the main results of the study.

PMID- 15484754
TI  - Odour emission inventory of German wastewater treatment plants--odour flow rates
      and odour emission capacity.
AB  - Wastewater Treatment plants can cause odour emissions that may lead to
      significant odour annoyance in their vicinity. Thus, over the past 20 years,
      several measurements were taken of the odour emissions that occur at WWTPs of
      different sizes, treatment technology, plant design and under different operating
      conditions. The specific aspects of odour sampling and measurement have to be
      considered. I presented some of the results of my odour emission measurements 11
      years ago. However, it is now necessary to update the figures by evaluating newer
      measurement results obtained from measurements taken from 1994 to 2003. These are
      presented in this paper. Also, the paper highlights the odour emission capacity
      (OEC) measurement technique which characterises liquids and can be used to assess
      the results achieved by different types of treatment in the liquid phase, e.g. in
      a sewerage system. In addition, the OEC is a suitable parameter to set standards
      for the odorant content of industrial wastewaters that are discharged into the
      publicly owned sewerage system.

PMID- 15484755
TI  - Interlaboratory comparison of olfactometry in Japan.
AB  - In 2000, 2001, and 2002, interlaboratory comparison of olfactometry was carried
      out in order to collect basic data for the establishment of a quality control
      procedure and the determination of quality criteria for the triangular odour bag
      method. In 2000, interlaboratory comparison was conducted by using a measurement
      method for samples taken at smoke stacks. On the other hand, the measurement
      method for samples taken at boundary lines was used for interlaboratory
      comparison in 2001. A total of seven olfactometry laboratories in Japan
      participated in each test, and mean values, repeatability standard deviations,
      reproducibility standard deviations, and standard deviations under intermediate
      conditions of detection threshold of ethyl acetate were calculated from the
      results. These values can be used in a quality control process of olfactometry.
      In 2002, interlaboratory comparison was carried out by using a measurement method
      for samples taken at smoke stacks. A total of 137 olfactometry laboratories in
      Japan participated in the test, and 69% of them lay within the permissible range
      of the odour index.

PMID- 15484756
TI  - Mass-producible and wireless wide-area networks of electronic noses: problems and
      solutions.
AB  - This paper focuses on the development of a wide-area network of wireless
      electronic noses and the solutions found to the problems encountered, both of a
      technical nature and the management involved when employing large amounts of
      field units. Examples of field test results are given, to illustrate the
      abilities of such a system.

PMID- 15484757
TI  - Hydrogen sulfide emission in sewer networks: a two-phase modeling approach to the
      sulfur cycle.
AB  - Wherever transport of anaerobic wastewater occurs, potential problems associated
      with hydrogen sulfide in relation to odor nuisance, health risk and corrosion
      exist. Improved understanding of prediction of hydrogen sulfide emission into the
      sewer atmosphere is needed for better evaluation of such problems in sewer
      networks. A two-phase model for emission of hydrogen sulfide along stretches of
      gravity sewers is presented to estimate the occurrence of both sulfide in the
      water phase and hydrogen sulfide in the sewer atmosphere. The model takes into
      account air-water mass transfer of hydrogen sulfide and interactions with other
      processes in the sulfur cycle. Various emission scenarios are simulated to
      illustrate the release characteristics of hydrogen sulfide.

PMID- 15484758
TI  - Integrated odour modelling for sewage treatment works.
AB  - Odours from sewage treatment works are a significant source of environmental
      annoyance. There is a need for tools to assess the degree of annoyance caused,
      and to assess strategies for mitigation of the problem. This is the role of odour
      modelling. Four main stages are important in the development of an odour problem.
      Firstly, the odorous molecules must be formed in the liquid phase. They must then
      transfer from the liquid to the gaseous phase. They are then transported through
      the atmosphere to the population surrounding the odour source, and are then
      perceived and assessed by that population. Odour modelling as currently practised
      tends to concentrate on the transportation of odorants through the atmosphere,
      with the other areas receiving less attention. Instead, odour modelling should
      consider each stage in an integrated manner. This paper describes the development
      of integrated odour models for annoyance prediction. The models describe the
      liquid-phase transformations and emission of hydrogen sulphide from sewage
      treatment processes. Model output is in a form suitable for integration with
      dispersion models, the predictions of which can in turn be used to indicate the
      probability of annoyance. The models have been applied to both hypothetical and
      real sewage treatment works cases. Simulation results have highlighted the
      potential variability of emission rates from sewage treatment works, resulting
      from flow, quality and meteorological variations. Emission rate variations can
      have significant effects on annoyance predictions, which is an important finding,
      as they are usually considered to be fixed and only meteorological variations are
      considered in predicting the odour footprint. Areas for further development of
      integrated odour modelling are discussed, in particular the search for improved
      links between analytical and sensory measurements, and a better understanding of
      dose/response relationships for odour annoyance.

PMID- 15484759
TI  - Modelling to assist in wastewater collection system odour and corrosion potential
      evaluations.
AB  - Odour emissions and corrosion concerns can be a constant focus for many
      wastewater treatment and collection system owners, usually from the first day
      that their collection systems begin operation. Many sewer systems are reaching
      the end of their useful life, or have experienced either odour or corrosion
      issues. This paper shows a link between odour generation and corrosion potential,
      and how modelling can be used to assist in odour/corrosion assessments of
      existing wastewater collection systems. A model has been developed that is
      capable of predicting liquid-phase sulphide generation and subsequent release to
      overlying sewer headspace as hydrogen sulphide (H2S), where it can be the source
      of either odour or corrosion problems. This paper presents an overview of the
      model, and uses a case study involving both odour and corrosion issues to
      demonstrate the utility in modelling. The model was used to identify potential
      locations within the system where odour/corrosion may be problematic, as well as
      assisting in the evaluation of potential odour control alternatives.

PMID- 15484760
TI  - Chemical sulfide oxidation of wastewater--effects of pH and temperature.
AB  - In this study, the kinetics and stoichiometry of chemical sulfide oxidation of
      wastewater from sewer networks were investigated. Based on experiments, it was
      shown that the stoichiometry could be considered identical for wastewater from
      two sampling sites. However, the kinetics differed significantly among the
      wastewaters from the two sites. Effects of pH and temperature were investigated
      in the pH and temperature ranges 5-9 and 5-25 degrees C, respectively. The rate
      of chemical sulfide oxidation could be related to the dissociation of H2S to HS-,
      with HS- being oxidized at a higher rate than H2S. The temperature dependency of
      the chemical sulfide oxidation rate was described using an Arrhenius
      relationship. The oxidation rate was found to double with a temperature increase
      of 12 degrees C. The stoichiometry of the chemical oxidation was not
      significantly affected by varying pH and temperature. Based on the experiments, a
      general rate equation, including a stoichiometric coefficient describing chemical
      sulfide oxidation in wastewater was proposed, enabling the process to be
      incorporated into sewer process models that can predict odor and corrosion
      problems.

PMID- 15484761
TI  - Removal of target odorous molecules on to activated carbon cloths.
AB  - Activated carbon materials are adsorbents whose physico-chemical properties are
      interesting for the treatment of odorous compounds like hydrogen sulfide. Indeed,
      their structural parameters (pore structure) and surface chemistry (presence of
      heteroatoms such as oxygen, hydrogen, nitrogen, sulfur, phosphorus) play an
      important role in H2S removal. The cloth texture of these adsorbents (activated
      carbon cloths) is particularly adapted for dealing with high flows, often found
      in the treatment of odor emissions. Thus, this paper first presents the influence
      of these parameters through adsorption isothermal curves performed on several
      materials. Secondly, tests in a dynamic system are described. They highlight the
      low critical thickness of the fabric compared to granular activated carbon.

PMID- 15484762
TI  - Hydrogen sulphide removal by activated sludge diffusion.
AB  - Odours from wastewater treatment plants comprise a mixture of various gases, of
      which hydrogen sulphide (H2S) is the main constituent. Microorganisms commonly
      found in wastewater can degrade sulphurous compounds. Therefore, the use of
      activated sludge (AS) for odour control offers an alternative to traditional
      waste gas treatment processes, such as biofilters, bioscrubbers and biotrickling
      filters, both in practical terms (use of existing facilities) and economically
      (minimal capital cost). The performance of AS diffusion as a bioscrubber for
      removing H2S at concentrations at 25, 75 and 150 ppmv was evaluated. Pilot-scale
      trials were undertaken using parallel 60-L aeration tanks and 20-L clarifier
      reactors at the Bedford Sewage Treatment Works, Carington, UK. Olfactometry
      measurements were also carried out to determine whether there was any increase in
      odour concentration owing to H2S diffusion. Hydrogen sulphide removal rates of
      100% were obtained, with no noticeable increase in odour concentration throughout
      the trials as measured by olfactometry. Odour concentration was highest at the
      beginning of the trials and lowest during the high H2S dosing period, with
      similar values being obtained for test and control. It was concluded that AS
      diffusion is an effective bioscrubber for the removal of H2S odour.

PMID- 15484763
TI  - Plant oils thymol and eugenol affect cattle and swine waste emissions
      differently.
AB  - Wastes generated from the production of cattle and swine in confined facilities
      create the potential for surface and groundwater pollution, emission of
      greenhouse gases, transmission of pathogens to food and water sources, and odor.
      It is our hypothesis that something which inhibits microbial fermentation in
      livestock wastes will be beneficial to solving some of the environmental
      problems. Our work has concentrated on the use of antimicrobial plant oils,
      thymol, thyme oil, carvacrol, eugenol and clove oil. Anaerobic one-litre flasks
      with a working volume of 0.5 L cattle or swine manure were used to evaluate the
      effect of thymol and eugenol on production of fermentation gas, short-chain
      volatile fatty acids, lactate, and bacterial populations. Either oil at 0.2% in
      both wastes essentially stopped all production of gas and volatile fatty acids,
      and eliminated all fecal coliform bacteria. In cattle but not swine waste, thymol
      prevented the accumulation of lactate. However, eugenol stimulated lactate
      formation in cattle and swine wastes. Thus, eugenol may offer a distinct
      advantage over thymol, because lactate accumulation in the wastes causes the pH
      to drop more rapidly, further inhibiting microbial activity and nutrient
      emissions. We conclude that plant oils may offer solutions to controlling various
      environmental problems associated with livestock wastes, assuming that they are
      cost-effective.

PMID- 15484764
TI  - A membrane bioreactor for the removal of dimethyl sulphide and toluene from waste
      air.
AB  - In biotrickling filters, mass transfer of hydrophobic compounds is the limiting
      factor. Biofilters are static systems, and so control and regulation of
      operational parameters such as pH and nutrient supply can be a problem. In
      membrane bioreactors, these drawbacks can be avoided. The hydrophobic membrane
      separates the waste air from the aqueous phase, thus avoiding mass-transfer
      limitation, while pH and nutrient supply can be directly controlled. In this
      contribution, an overview will be given of results obtained during a four-year
      project. First, the physical chemical characteristics (solubility, permeability,
      diffusivity) and microbial adhesion of different membranes were tested. This led
      to the selection of a composite membrane consisting of a porous
      polyvinylidenefluoride (PVDF) support layer coated with a thin (1 or 2.5 microm)
      dense polydimethylsiloxane (PDMS) top layer. This membrane was mounted into a
      module provided with four parallel rectangular channels for gas flow (in contact
      with the porous layer) and nutrient solution (in contact with the dense layer)
      respectively. After inoculation, a biofilm developed on the dense layer.
      Experiments were performed with dimethyl sulphide and toluene as target VOCs.
      Operational characteristics such as elimination capacity as a function of the
      volumetric load and residence time, effect of nutrient supply, long-term
      performance) were determined. Mass transfer was studied by measuring
      concentration profiles along the channels of the module in different conditions.

PMID- 15484765
TI  - Developing methods to evaluate odour control products.
AB  - An economical and practical alternative to the standard end-of-pipe odour control
      methods is the application of liquid odour control products. Currently, there are
      no established product-testing methods. The data that are available are often of
      questionable quality and may have limited relevance to waste management. Waste
      facilities receive differing streams of waste at varying loading volumes. Whilst
      in operation this exposes control products to a wide variety of environmental
      conditions, further increasing the difficulty of selecting an effective means of
      control. The current study initially identifies commercially available odour
      control products applicable for solid and liquid waste management operations.
      Bench-scale batch absorption tests have been carried out to investigate odorous
      gas abatement for a range of selected commercial products and water at a range of
      pH values. Hydrogen sulphide was the test odorous gas, as it is commonly
      associated with waste processes. Gas-phase volumetric mass-transfer coefficients
      (KGa) have been calculated to determine mass-transfer performance. The
      development of a pilot-scale spray tower is then presented as the testing
      apparatus for future work. This is an attempt to construct a repeatable testing
      method for evaluating abatement performance of odour control products, and
      control the problems encountered when applying odour control products to open
      sites. KGa values and data collected from tests in this study will be considered
      in future work as design parameters for the rig.

PMID- 15484766
TI  - Volatile organic compound adsorption in a gas-solid fluidized bed.
AB  - Fluidization finds many process applications in the areas of catalytic reactions,
      drying, coating, combustion, gasification and microbial culturing. This work aims
      to compare the dynamic adsorption characteristics and adsorption rates in a
      bubbling fluidized bed and a fixed bed at the same gas flow-rate, gas residence
      time and bed height. Adsorption with 520 ppm methanol and 489 ppm isobutane by
      the ZSM-5 zeolite of different particle size in the two beds enabled the
      differentiation of the adsorption characteristics and rates due to bed type,
      intraparticle mass transfer and adsorbate-adsorbent interaction. Adsorption of
      isobutane by the more commonly used activated carbon provided the comparison of
      adsorption between the two adsorbent types. With the same gas residence time of
      0.79 seconds in both the bubbling bed and fixed bed of the same bed size of 40 mm
      diameter and 48 mm height, the experimental results showed a higher rate of
      adsorption in the bubbling bed as compared to the fixed bed. Intraparticle mass
      transfer and adsorbent-adsorbate interaction played significant roles in
      affecting the rate of adsorption, with intraparticle mass transfer being more
      dominant. The bubbling bed was observed to have a steeper decline in adsorption
      rate with respect to increasing outlet concentration compared to the fixed bed.
      The adsorption capacities of zeolite for the adsorbates studied were
      comparatively similar in both beds; fluidizing, and using smaller particles in
      the bubbling bed did not increase the adsorption capacity of the ZSM-5 zeolite.
      The adsorption capacity of activated carbon for isobutane was much higher than
      the ZSM-5 zeolite for isobutane, although at a lower adsorption rate. Fourier
      transform infra-red (FTIR) spectroscopy was used as an analytical tool for the
      quantification of gas concentration. Calibration was done using a series of
      standards prepared by in situ dilution with nitrogen gas, based on the ideal gas
      law and relating partial pressure to gas concentration. Concentrations up to 220
      ppm for methanol and 75 ppm for isobutane were prepared using this method.

PMID- 15484767
TI  - Comparison of different TiO2 photocatalysts for the gas phase oxidation of
      volatile organic compounds.
AB  - Gas-solid photocatalyzed oxidation of air contaminants is being explored more and
      more for possible application to decontamination, purification and deodorization
      of enclosed atmospheres. Indoor air is characterized by a huge number of
      pollutants at low concentrations. Volatile organic compounds (VOC) represent the
      main indoor air pollutants category, and are of great concern since some of them
      can act negatively on human health. Several treatments exist to reduce VOC
      concentrations in gaseous effluents, but photocatalytic oxidation appears to be
      the most appropriate regarding indoor air specific constraints. It is then
      necessary to develop photocatalysts, which can possibly be used in an application
      such as indoor air-quality improvement. In the present work, three different TiO2
      based materials were studied and compared for the photocatalytic oxidation of a
      typical pollutant of indoor air: methyl ethyl ketone. Kinetic studies were
      performed for each material in dry and humid air conditions, and the Langmuir
      Hinshelwood model was satisfactorily applied in almost every case. A second
      approach consisted of determining methyl ethyl ketone degradation by-products.
      Acetaldehyde was found to be the main gaseous intermediate, and could be taken
      into account in the general Langmuir-Hinshelwood modeling.

PMID- 15484768
TI  - Photocatalytic degradation of toluene by platinized titanium dioxide
      photocatalysts.
AB  - A photoreactor has been set up to study the photodegradation of volatile organic
      compound (VOC) in situ. In the reactor, TiO2 and Pt/TiO2 photocatalysts were
      immobilized on to UV-transparent quartz support. Scanning electron microscope
      (SEM) studies and Brunauer-Emmett-Teller (BET) surface area measurements revealed
      that the quartz fiber support was mostly coated with catalyst with a total
      surface area of 4.0 +/- 0.3 m2/g. The photocatalytic activity of the
      photocatalysts was evaluated for the photodegradation of 160 ppm toluene-laden
      air. It was found that 50-70% of toluene was degraded within the first 5 min of
      UV illumination. Both TiO2 and Pt/TiO2 photocatalysts suffered from deactivation
      after 18 hours of continuous operation, and the photocatalysts' activity was
      significantly reduced. However, platinization doubled the photocatalyst life and
      delayed the onset of de-activation. The presence of moisture was found to shift
      the onset of catalyst de-activation to an earlier time. It is concluded that the
      de-activation of the photocatalyst was due to the accumulation of intermediates
      on the photocatalysts surface preventing the toluene being adsorbed on the
      photocatalyst surface for degradation.

PMID- 15484769
TI  - The development of experimental procedures for the evaluation of additives to
      attenuate manure odour, and the impact of these additives on workers, animals and
      the environment.
AB  - The objective of this project was to develop a laboratory research protocol to
      evaluate the effect of additives on manure odour and physico-chemical
      characteristics, and establish conditions that are representative of those found
      in farm storage structures (temperature, solids content, pH, ventilation above
      the manure surface, storage period). The results suggested that system
      configuration might have an impact on additive effect. An open system should be
      used when it is recommended that additives be applied in the animal diet or the
      gutters. Additionally, the surface/depth ratio of the gutter should be respected,
      since it will impact on the relative importance of the aerobic layer and on
      ammonia volatilization. On the other hand, a closed system should be used when
      the additive is applied to the manure storage tank, especially if the tank has a
      cover. Odour analysis still requires fundamental research to establish reliable
      procedures and protocols, especially in the area sample collection and dilution
      levels required to decrease H2S concentration to safe levels for the panellists.
      Odour analysis should also be conducted in triplicate, because of the possible
      large experimental error due to dilution, the human factors, and also
      instrumental error.

PMID- 15484770
TI  - Use of hydrogen peroxide in scrubbing towers for odor removal in wastewater
      treatment plants.
AB  - The aim of this work was to replace sodium hypochlorite (NaCIO) with hydrogen
      peroxide (H202) in chemical scrubbing towers, in order to avoid the formation of
      chlorinated species, harmful for human health. Some previous studies have already
      shown the ability of H2O2 to treat the hydrogen sulfide (H2S) pollution. However,
      an important decomposition of the oxidant was observed in the scrubbing solution
      (carbonates, transition metal and high pH are responsible for this decomposition)
      leading to high reactant consumption. Consequently, this study first focused on
      research into a compound able to reduce the hydrogen peroxide degradation.
      Experiments were conducted on a pilot unit (3,000 m3 h(-1)) in a wastewater
      treatment plant. The sodium silicate (Na2SiO3) proved to be a good scrubbing
      solution stabilizer. A very good removal of hydrogen sulfide (up to 98%) was also
      obtained. Finally, the study resulted in the determination of the best operating
      conditions to achieve both an efficient and economical process.

PMID- 15484771
TI  - Odour and ammonia removal from pig house exhaust air using a biotrickling filter.
AB  - Odour from agricultural activities, such as the spreading of manure and the
      housing of animals, is increasingly being considered a nuisance in densely
      populated countries like the Netherlands. The objective of this research was to
      study the odour removal from pig house exhaust air by a biotrickling filter that
      had been implemented for ammonia abatement. At a regular pig production farm, the
      performance of a running full-scale biotrickling filter was studied for 72 days.
      Ammonia and odour removal efficiency were on average 79% and 49% respectively.
      Ammonia removal appeared to be based on an unintended accumulation of ammonium
      and nitrite in the system, instead of on production and discharge of nitrate. The
      odour removal efficiency showed a large variation that, for a major part, about
      80%, could be attributed to actual changes in the performance of the biotrickling
      filter. These changes were probably caused by variations in the composition of
      the air that were not completely reflected by the olfactometrically measured
      odour concentration, as the many different components that make up the odour each
      have different removal characteristics. It seemed that the biotrickling filter
      was operated below its maximum absolute odour removal capacity [OUE/(m3
      filter)/s], which means that the absolute odour removal will probably rise at
      increasing load. It was, however, not possible to distinguish between the
      influence of either the odour load or the odour concentration on the odour
      removal, because of a positive correlation between the odour concentration and
      the air flow. To increase the odour removal efficiency (%), the design of the
      filter probably needs to be optimised for both well and poorly water-soluble
      odour components.

PMID- 15484772
TI  - Biological treatment of ammonia gas at high loading.
AB  - The exhaust gas from compost processing plants contains a large amount of
      ammonia. To treat ammonia gas at high loads, bench-scale experiments were carried
      out. First, nitrifying bacteria were enriched from soil and immobilized on porous
      ceramics. The ceramics were packed in an acrylic cylinder (diameter, 100 mm;
      packed height, 190 mm) and ammonia gas was introduced to the top of the cylinder.
      The concentration and flow rate of ammonia gas were gradually increased and
      finally 85 ppm was introduced at a space velocity of 800 h(-1) (empty bed
      residence time (EBRT), 4.5 sec). The ammonia load was 1.0 kg N/m3 day(-1). The
      exhaust contained 1.5-2 ppm of ammonia. Then the packed ceramics were transferred
      to another acrylic cylinder (diameter, 50 mm; packed height, 800 mm). A high
      concentration of ammonia gas (1,000 ppm) was introduced at a space velocity of 96
      h(-1) (ammonia loading, 1.44 kg N/m3 day(-1); EBRT, 37.5 sec). The exhaust
      contained 2 ppm of ammonia (removal rate, 99.8%). The packed bed was washed with
      water intermittently or continuously, and the wastewater from the cylinder
      contained a large amount of ammonium and nitrate ions of at a 1:1 ratio.
      Stoichiometric analysis showed that half of the introduced ammonia was oxidized
      to nitrate, and the rest was converted to ammonium ion. Thus, ammonia gas was
      effectively treated at a high load by biofiltration with nitrifying bacteria.

PMID- 15484773
TI  - Removal of odorous sulphur-containing gases by a new isolate from activated
      sludge.
AB  - Biological treatment of odorous sulphur-containing compounds is attracting
      attention due to its benign eco-friendliness, energy-savings and low operating
      costs. As the biological treatment efficiency of dimethylsulphide (DMS) reported
      was often low and variable, selection of useful DMS-degrading microorganisms is
      of importance for the enhancement of the biological deodorizing process. This
      paper reports the successful isolation of a DMS-degrading bacterium from
      activated sludge, using the enrichment isolation technique. The isolate was
      identified by 16S rRNA gene sequencing, and found to belong to the alpha group of
      Proteobacteria, with an identity of 99.4% and 99.1% to the 16S rRNA gene
      sequences of Afipia felis and Pseudomonas carboxydohydrogena, respectively. The
      isolate was able to metabolize DMS as well as hydrogen sulphide (H2S). A batch
      experiment was performed to assess the removal characteristics of DMS by the
      isolate. The results showed that over half of DMS could be removed by the isolate
      in 3 hours when the initial DMS amount was approximately 10 micromol and 25
      micromol. Removal of H2S by the isolate was evaluated by a continuous test in a 2
      L gas-bubbling bottle. Although part of the H2S removal by the mineral medium
      itself was observed in the control test, the majority of H2S removal was believed
      to be attributed to the metabolic activity of the isolate. In conclusion, the
      isolate might be potentially useful for the enhancement of the biological
      deodorizing processes.

PMID- 15484774
TI  - Batch experiment on H2S degradation by bacteria immobilised on activated carbons.
AB  - Biological treatments of odorous compounds, as compared to chemical or physical
      technologies, are in general ecologically and environmentally favourable.
      However, there are some inefficiencies relative to the media used in
      biofiltration processes, such as the need for an adequate residence time; the
      limited lifetime, and pore blockage of media, which at present render the
      technology economically non-viable. The aim of the study is to develop novel
      active media to be used in performance-enhanced biofiltration processes, by
      achieving an optimum balance and combination of the media adsorption capacity
      with the biodegradation of H2S through the bacteria immobilised on the media. An
      enrichment culture was obtained from activated sludges in order to metabolise
      thiosulphate. Batch-wise experiments were conducted to optimise the bacteria
      immobilisation on activated carbon, so as to develop a novel "biocarbon". Biofilm
      was mostly developed through culturing the bacteria with the presence of carbons
      in mineral media. SEM and BET tests of the carbon along with the culturing
      process were used to identify, respectively, the biofilm development and
      biocarbon porosity. Breakthrough tests evaluated the biocarbon performance with
      varying gas resistance time, inlet H2S concentration, and type of support
      materials. Fundamental issues were discussed, including type of support material,
      mode of bacteria immobilisation, pore blockages, and biodegradation kinetics,
      etc. This batch-wise study provides a basis for our future research on
      optimisation of the biofiltration process using a bio-trickling reactor.

PMID- 15484775
TI  - Technical and economical analysis of the conversion of a full-scale scrubber to a
      biotrickling filter for odor control.
AB  - The present paper evaluates the technical and economical feasibility of
      converting wet chemical scrubbers to biotrickling filters for H2S control at the
      Orange County Sanitation District (OCSD), California. Results of 8 months of
      continuous operation of a biotrickling filter treating 16,000 m3 h(-1) of foul
      air are analyzed. The reactor was operated at a gas contact time of 1.6 to 2.2
      seconds reaching H2S elimination capacities up to 105-110 g H2S m3 h(-1),
      consistently maintaining outlet concentrations well below the regulatory limits
      (24 h average of 1 ppmv) and demonstrating to be very robust against temporary
      changes. Also, a cost-benefit analysis of the conversion was performed. Savings
      from chemicals, energy and water usage compared to a chemical scrubber operated
      in parallel to the biotrickling filter throughout the project indicated that the
      payback time of the conversion was about 1.3 years. Cost savings ranged between
      40,000 US dollars per year, per scrubber. While the above number may be specific
      to OCSD conditions, the cost analysis suggests that there is a significant
      benefit of converting chemical scrubbers to biotrickling filters over a wide
      range of operating conditions.

PMID- 15484776
TI  - Biotechnology-based odour control: design criteria and performance data.
AB  - As neighbouring areas continue to encroach upon wastewater treatment plants,
      there is an increasing need for odour control to mitigate potential negative
      offsite odorous impacts. One technology that is gaining widespread acceptance is
      biotechnology, which utilises the inherent ability of certain microorganisms to
      biodegrade offensive odorous compounds. Two main advantages of this form of
      treatment over other odour control technologies include the absence of hazardous
      chemicals and relatively low operation and maintenance requirements. The purpose
      of this paper is to provide information related to odour control design criteria
      used in sizing/selecting biotechnology-based odour control technologies, and to
      provide odour removal performance data obtained from several different
      biotechnology-based odour control systems. CH2M HILL has collected biotechnology
      based odour control performance data over the last several years in order to
      track the continued performance of various biofilters and biotowers over time.
      Specifically, odour removal performance data have been collected from soil-,
      organic- and inorganic-media biofilters and inert inorganic media biotowers.
      Results indicate that biotechnology-based odour control is a viable and
      consistent technology capable of achieving high removal performance for odour and
      hydrogen sulphide. It is anticipated that the information presented in this paper
      will be of interest to anyone involved with odour control technology
      evaluation/selection or design review.

PMID- 15484777
TI  - Odour abatement in the integrated reactor concept for simultaneous treatment of
      liquid and solid pig manure fractions.
AB  - New technologies are needed for manure treatment that can capture nutrients,
      reduce emissions of ammonia and nuisance odours, and kill harmful pathogens. A
      reactor concept was developed for simultaneous treatment of separately collected
      liquid and solid fractions of pig manure. The liquid fraction is concentrated by
      evaporating the water using energy from the composting system and at the same
      time scrubbing ammonia from the composting off-gas by acidifying the urine to pH
      4 with nitric acid. This results in two marketable products, a concentrated
      liquid nitrogen fertiliser (NH4NO3) without phosphorus, and a stabilised, solid
      organic fertiliser, which is free of pathogens and weeds. By connecting the two
      reactor systems, emissions of ammonia and odours are abated as ammonia emitted
      from the composting is trapped in the liquid fraction and odorous compounds
      emitted from the liquid are degraded in the composting reactor. The concept was
      physically simulated by coupling a 80-L compost reactor to a 10-L bubble column.
      Operation of the bench-scale system showed that the concept is very promising.
      All nutrients were captured, and emissions of ammonia and odours were almost
      completely abated.

PMID- 15484779
TI  - Anoxic control of odour and corrosion from sewer networks.
AB  - Anoxic processes can effectively control odour and corrosion in sewer networks.
      However, the absence of fundamental knowledge on the kinetics of anoxic
      transformation of sewage prevents the engineering applications of anoxic control
      in sewers. This paper focuss on a basic understanding of the anoxic
      transformations needed for a conceptual simulation of the water phase processes.
      Experiments conducted in batch reactors have shown that nitrite builds up in
      wastewater during denitrification. Part of the nitrate-reducing biomass is
      capable of utilizing nitrite after nitrate is depleted. Compared with aerobic
      transformation, anoxic processes have low values of maximum growth rate of the
      biomass and also a low endogenous respiration rate. Heterotrophic yield
      determined under anoxic conditions, at level of 0.25 mmol e-eq (mmol e-eq)(-1),
      accounted for less than 40% of the corresponding aerobic values.

PMID- 15484778
TI  - The effect of two ammonia-emission-reducing pig housing systems on odour
      emission.
AB  - Odour nuisance from agricultural activities is increasing in densely populated
      countries like the Netherlands. To develop adequate regulations, a large-scale,
      government-financed monitoring programme was started in the mid-1990s to
      establish odour emission levels for both conventional and low ammonia emission
      housing systems for cattle, pigs and poultry. The results indicate that high- and
      low-odour emission housing are difficult to distinguish because of the large
      variation within housing systems. Measurements on different farm locations within
      the same housing system show both a large variation between locations and within
      one location (in time). The latter, however, is significantly smaller, which
      suggests that farm management is an important determinant in odour emission that
      interferes with the effects of housing systems. The current research was aimed at
      determining the effect of two common ammonia-reducing pig-housing systems on
      odour emissions compared to conventional housing systems under similar management
      conditions. The respective reduction principles of these systems are reducing the
      emitting surface of the manure pit and cooling of manure in the manure pit (both
      pits beneath slatted floor). Five farms that combined conventional housing with
      one low-ammonia system (three reduced emitting surface and two manure cooling)
      were selected for a direct, pair-wise comparison of (olfactometric) odour
      emission measurements. The results show a highly significant effect (p < 0.01)
      for two of the three reduced emitting surface systems and for one of the two
      manure cooling system. The average odour reduction percentages of these systems
      are 35% (from 24.9 to 16.0 OUE/s per animal) and 23% (from 30.1 to 24.0 OUE/s per
      animal) respectively. Although odour emission reduction through the type of
      housing system is possible, management factors interact with the system and
      thereby determine whether the system reduces odour emission or not.

PMID- 15484780
TI  - Legal concerns with concierge practices.

PMID- 15484781
TI  - Leadership strategy: engage the key players in health care. Ideas and challeges
      from the MSMS leadership summit.

PMID- 15484782
TI  - Profile in practice success: Henry Ford blends research flair with patient care.

PMID- 15484783
TI  - Recognizing patients with drug seeking behavior.

PMID- 15484784
TI  - What is the prescription for a healthier Michigan? Annual scientific meeting
      explores answers.

PMID- 15484785
TI  - CDC issues new influenza recommendations for 2004-2005 flu season.

PMID- 15484786
TI  - Influenza Sentinel Provider Surveillance in Michigan.

PMID- 15484787
TI  - Influenza vaccination strategies.

PMID- 15484788
TI  - Using reminder/recall as an immunization intervention strategy works.

PMID- 15484789
TI  - Influenza vaccination of health care workers "first, do no harm"....

PMID- 15484790
TI  - Let's get the gang together!

PMID- 15484791
TI  - Use of pulsed-field gel electrophoresis for a pseudoepidemic of Clostridium
      difficile infections in a pediatric oncology and hematology department.

PMID- 15484792
TI  - Infections due to group B streptococci in neonates are not associated with higher
      mortality than infections due to other organisms.

PMID- 15484793
TI  - Large infection problems in small patients merit a renewed emphasis on
      prevention.

PMID- 15484794
TI  - Molecular epidemiology of Serratia marcescens outbreaks in two neonatal intensive
      care units.
AB  - OBJECTIVE: Serratia marcescens can cause serious infections in patients in
      neonatal intensive care units (NICUs), including sepsis, pneumonia, urinary tract
      infection, and conjunctivitis. We report the utility of genetic fingerprinting to
      identify, investigate, and control two distinct outbreaks of S. marcescens.
      DESIGN: An epidemiologic investigation was performed to control two clusters of
      S. marcescens infections and to determine possible routes of transmission.
      Molecular typing by pulsed-field gel electrophoresis determined the relatedness
      of S. marcescens strains recovered from neonates, the environment, and the hands
      of healthcare workers (HCWs). SETTING: Two geographically distinct level III-IV
      NICUs (NICU A and NICU B) in two university-affiliated teaching hospitals in New
      York City. RESULTS: In NICU A, one major clone, "F," was detected among isolates
      recovered from four neonates and the hands of one HCW. A second predominant
      clone, "A," was recovered from four sink drains and one rectal surveillance
      culture from an asymptomatic neonate. In NICU B, four neonates were infected with
      clone "D," and three sink drains harbored clone "H." The attributable mortality
      rate from bloodstream infections was 60% (3 of 5 infants). The antimicrobial
      susceptibilities of clone F strains varied for amikacin, cefepime, and
      piperacillin/tazobactam. CONCLUSIONS: S. marcescens causes significant morbidity
      and mortality in preterm neonates. Cross-transmission via transient hand carriage
      of a HCW appeared to be the probable route of transmission in NICU A. Sinks did
      not harbor the outbreak strains. Antimicrobial susceptibility patterns did not
      prove to be an accurate predictor of strain relatedness for S. marcescens.

PMID- 15484795
TI  - Clustering of Serratia marcescens infections in a neonatal intensive care unit.
AB  - OBJECTIVES: To study clusters of infections caused by Serratia marcescens in a
      neonatal intensive care unit (NICU) and to determine risk factors for S.
      marcescens infection or colonization. DESIGN: Genotyping of S. marcescens
      isolates was performed by pulsed-field gel electrophoresis (PFGE). A
      retrospective case-control study was conducted. SETTING: A tertiary-care
      pediatric hospital with a 16-bed NICU. PATIENTS: All neonates with at least one
      culture positive for S. marcescens in the NICU during December 1999 to July 2002.
      Case-patients (n = 11) treated in the NICU during December 1999 to February 2000
      were included in the case-control study. Neonates treated in the NICU for at
      least 72 hours during the same period with cultures negative for S. marcescens
      were used as control-patients (n = 27). RESULTS: S. marcescens was cultured from
      19 neonates; 9 were infected and 10 were colonized. PFGE analysis identified
      three epidemic strains; each cluster consisted of identical isolates, except one
      isolate in the first cluster that was different. The risk factors identified were
      low birth weight, prematurity, prolonged respiratory therapy, prolonged use of
      antibiotics, and maternal infection prior to delivery. Overcrowding and
      understaffing were recorded simultaneously with the clusters. CONCLUSIONS: PFGE
      analysis showed three independent clusters. Several factors contributed to spread
      of the epidemic strains: (1) there were many severely premature and susceptible
      neonates, (2) the NICU was overcrowded during the clusters, and (3) transmission
      was likely to occur via the hands of staff. Cohorting and improvement of routine
      infection control measures led to the cessation of each cluster.

PMID- 15484796
TI  - Rapid eradication of a cluster of Serratia marcescens in a neonatal intensive
      care unit: use of epidemiologic chromosome profiling by pulsed-field gel
      electrophoresis.
AB  - OBJECTIVE: To investigate a cluster of patients infected and colonized with
      Serratia marcescens in a neonatal intensive care unit (NICU). METHODS: In June
      2001, two neonates in the NICU had clinical infections with S. marcescens and one
      died. Infection control surveillance data for the NICU revealed that S.
      marcescens was rarely isolated from clinical specimens. Surveillance and
      environmental cultures were performed and isolates were typed using pulsed-field
      gel electrophoresis. Staff and neonates were cohorted and a waterless, alcohol
      based handwashing agent was introduced. A case-control study was performed.
      RESULTS: From June 2 through August 20, 2001, 11 neonates with S. marcescens
      infection and colonization were identified. The incidence of S. marcescens
      infections increased from 0.19 per 1,000 patient-days in 2000 to 0.52 per 1,000
      patient-days in 2001 (P < .0001). In the first 3 weeks of the investigation,
      there were 2 sets of patients and sinks with indistinguishable strains; however,
      in subsequent weeks, all isolates were of unique strains, signifying no further
      transmission of the two initial predominant strains. Neonates with S. marcescens
      were more likely to have a lower gestational age and birth weight. There was no
      association between cases and healthcare workers (HCWs). CONCLUSIONS: A cluster
      of S. marcescens was quickly terminated after the introduction of preventive
      measures including cohorting of infected and colonized neonates and HCWs, contact
      precautions, surveillance cultures, and a waterless, alcohol-based hand
      antiseptic. Chromosomal typing determined that strains with an indistinguishable
      pattern were no longer present in the unit after control measures were
      implemented.

PMID- 15484797
TI  - Antimicrobial use and the influence of inadequate empiric antimicrobial therapy
      on the outcomes of nosocomial bloodstream infections in a neonatal intensive care
      unit.
AB  - OBJECTIVE: To evaluate antimicrobial use and the influence of inadequate empiric
      antimicrobial therapy on the outcomes of nosocomial bloodstream infections
      (BSIs). DESIGN: Prospective cohort study with nested case-control analysis.
      SETTING: Neonatal intensive care unit (NICU). METHODS: All patients weighing
      2,000 g or less were enrolled. Data collection included risk factors for
      nosocomial BSI, admission severity of illness, microbiology, antimicrobial
      therapy, and outcomes. Inadequate empiric antimicrobial therapy was defined as
      the use of antibiotics for more than 48 hours after the day that blood cultures
      were performed that did not cover the microorganisms causing the bacteremia or
      administration of antibiotics that failed to cover resistant microorganisms.
      RESULTS: Two hundred twenty-nine patients were enrolled. Forty-five developed
      nosocomial BSIs. The BSI rates were 11.2, 2.8, and 0 per 1,000 catheter-days for
      patients weighing 1,000 g or less, between 1,001 and 1,500 g, and between 1,501
      and 2,000 g, respectively. After adjustment for severity of illness, the
      mortality in patients with nosocomial BSI receiving inadequate empiric
      antimicrobial therapy was higher than in those receiving adequate therapy
      (adjusted odds ratio [AOR], 5.3; 95% confidence interval [CI95], 1.2-23.2). By
      multivariate analysis, nosocomial BSI attributed to Candida species (AOR, 6.3;
      CI95, 1.4-28.0) and invasive procedure prior to onset of BSI (AOR, 6.4; CI95, 1.0
      39.0) were associated with administration of inadequate empiric antimicrobial
      therapy. CONCLUSIONS: Administration of inadequate empiric antimicrobial therapy
      among NICU patients with nosocomial BSI was associated with higher mortality.
      Additional studies on the role of inadequate empiric antimicrobial therapy and
      the outcomes of BSIs among NICU patients are needed.

PMID- 15484798
TI  - Handwashing program for the prevention of nosocomial infections in a neonatal
      intensive care unit.
AB  - OBJECTIVE: To evaluate the effects of a hand hygiene program on compliance with
      hand hygiene and the rate of nosocomial infections in a neonatal intensive care
      unit (NICU). DESIGN: Open trial. SETTING: A level-III NICU in a teaching
      hospital. PARTICIPANTS: Nurses, physicians, and other healthcare workers in the
      NICU. INTERVENTIONS: A multimodal campaign for hand hygiene promotion was
      conducted beginning in September 1998. This program consisted of formal lectures,
      written instructions and posted reminders regarding hand hygiene and proper
      handwashing techniques, covert observation, financial incentives, and regular
      group feedback on compliance. Surveillance of handwashing compliance and
      nosocomial infections before and during the program was analyzed. RESULTS:
      Overall compliance with hand hygiene improved from 43% at baseline to 80% during
      the promotion program. The rate of nosocomial infections decreased from 15.13 to
      10.69 per 1,000 patient-days (P = .003) with improved handwashing compliance. In
      particular, respiratory tract infections decreased from 3.35 to 1.06 per 1,000
      patient-days during the handwashing campaign (P = .002). Furthermore, the
      correlation between nosocomial infection of the respiratory tract and handwashing
      compliance also reached statistical significance (r = -0.385; P = .014).
      CONCLUSIONS: Improved compliance with handwashing was associated with a
      significant decrease in overall rates of nosocomial infection and respiratory
      infections in particular. Washing hands is a simple, economical, and effective
      method for preventing nosocomial infections in the NICU.

PMID- 15484799
TI  - Survey of knowledge, beliefs, and practices of neonatal intensive care unit
      healthcare workers regarding nosocomial infections, central venous catheter care,
      and hand hygiene.
AB  - OBJECTIVE: To assess the knowledge, beliefs, and practices of neonatal intensive
      care unit (NICU) healthcare workers (HCWs). DESIGN: Self-administered survey.
      SETTING: A 55-bed NICU. PARTICIPANTS: NICU HCWs (N = 215). RESULTS: The response
      rate was 68%. Ninety-two percent knew central venous catheters (CVCs) should be
      capped, clamped, or connected to running fluids at all times. Ninety-five percent
      knew when to change gloves. Thirty-one percent knew the recommended duration for
      handwashing. Most HCWs believed sterile technique in CVC care (96%), gloves
      (91%), and handwashing (99%) prevent nosocomial infection (NI). Sixty-seven
      percent used sterile barriers to insert CVCs, 76% reported wearing gloves, 81%
      reported routine handwashing, 35% knew that bacterial hand counts are higher with
      rings, 30% knew that long fingernails are associated with higher gram-negative
      bacterial hand contamination, and 35% knew that artificial fingernails are
      associated with higher gram-negative bacterial hand contamination. Most (93%)
      believed HCWs can affect outcomes of patients with NIs. Fewer believed rings
      (40%), artificial fingernails (61%), and long fingernails (48%) play a role in
      NIs, or that policies concerning number of rings (50%), cutting fingernails
      (35%), or prohibiting artificial fingernails (47%) would prevent NIs. Sixty-one
      percent of HCWs regularly wore at least one ring to work, 56% wore their
      fingernails shorter than the fingertip, and 8% wore artificial fingernails.
      CONCLUSIONS: A disconnect existed between CVC knowledge and beliefs and practice.
      HCWs did not know the relationship between bacterial hand counts and rings and
      fingernails, and did not believe rings or long or artificial fingernails
      increased the risk of NIs.

PMID- 15484800
TI  - Ventilator-associated pneumonia in a pediatric intensive care unit in Saudi
      Arabia: a 30-month prospective surveillance.
AB  - OBJECTIVE: To describe the rate, risk factors, and outcome of ventilator
      associated pneumonia (VAP) in pediatric patients. METHODS: This prospective
      surveillance study of VAP among all patients receiving mechanical ventilation for
      48 hours or more admitted to a pediatric intensive care unit (PICU) in Saudi
      Arabia from May 2000 to November 2002 used National Nosocomial Infections
      Surveillance (NNIS) System definitions. RESULTS: Three hundred sixty-one eligible
      patients were enrolled. Most were Saudi with a mean age of 28.6 months. Thirty
      seven developed VAP. The mean VAP rate was 8.87 per 1,000 ventilation-days with a
      ventilation utilization rate of 47%. The mean duration of mechanical ventilation
      was 21 days for VAP patients and 10 days for non-VAP patients. The mean PICU stay
      was 34 days for VAP patients and 15 days for non-VAP patients. Among VAP
      patients, Pseudomonas aeruginosa was the most common organism, followed by
      Staphylococcus aureus. Other gram-negative organisms were also encountered. There
      was no significant difference between VAP and non-VAP patients regarding
      mortality rate. Witnessed aspiration, reintubation, prior antibiotic therapy,
      continuous enteral feeding, and bronchoscopy were associated with VAP. On
      multiple logistic regression analysis, only prior antibiotic therapy, continuous
      enteral feeding, and bronchoscopy were independent predictors of VAP.
      CONCLUSIONS: The mean VAP rate in this hospital was higher than that reported by
      NNIS System surveillance of PICUs. This study has established a benchmark for
      future studies of VAP in the pediatric intensive care population in Saudi Arabia.
      Additional studies from the region are necessary for comparison and development
      of preventive measures.

PMID- 15484801
TI  - Pattern of culture-proven neonatal sepsis in a district general hospital in the
      United Kingdom.
AB  - OBJECTIVE: To determine the incidence, clinical characteristics, and risk factors
      associated with the first culture-proven episode of sepsis among neonates in a
      neonatal intensive care unit (NICU). SETTING: Level-II NICU in the United
      Kingdom. PATIENTS: Neonates with their first culture-proven sepsis between
      January 1, 1996, and December 31, 2000. METHODS: Demographic data were obtained
      from the NICU database and chart review. Sepsis was considered early (EOS; < 72
      hours old) or late (LOS; > 72 hours old). Data were also collected on potential
      risk factors. RESULTS: Among 14,767 live births, 1,612 (11%) neonates were
      admitted to the NICU during the study period. Nine hundred eight were screened
      for sepsis. One hundred twenty-four had at least one positive culture (overall
      sepsis rate of 8.4 per 1,000 live births [1%] or 77 per 1,000 NICU admissions).
      Twenty-four neonates had EOS and 100 had LOS. Coagulase-negative staphylococci
      (CoNS) and group B Streptococcus were the most frequent organisms causing EOS,
      whereas CoNS and Escherichia coli most frequently caused LOS. Birth before 30
      weeks' gestation and birth weight less than 1,500 g were risk factors for sepsis.
      Resuscitation at birth was the leading risk factor for EOS and respiratory
      support prior to sepsis, presence of a central or peripheral catheter, and total
      parenteral nutrition were leading risk factors for LOS. CONCLUSIONS: A strong
      inverse relationship existed between gestational age of 30 weeks or younger and
      birth weight of 1,500 g or less and LOS. Resuscitation and indwelling intravenous
      catheters were also risk factors.

PMID- 15484802
TI  - Prevalence of nosocomial infections in Swiss children's hospitals.
AB  - OBJECTIVE: To acquire data on pediatric nosocomial infections (NIs), which are
      associated with substantial morbidity and mortality and for which data are
      scarce. DESIGN: Prevalence survey and evaluation of a new comorbidity index.
      SETTING: Seven Swiss pediatric hospitals. PATIENTS: Those hospitalized for at
      least 24 hours in a medical, surgical, intensive care, or intermediate care ward.
      RESULTS: Thirty-five NIs were observed among 520 patients (6.7%; range per
      hospital, 1.4% to 11.8%). Bacteremia was most frequent (2.5 per 100 patients),
      followed by urinary tract infection (1.3 per 100 patients) and surgical-site
      infection (1.1 per 100 patients; 3.2 per 100 patients undergoing surgery). The
      median duration until the onset of infection was 19 days. Independent risk
      factors for NI were age between 1 and 12 months, a comorbidity score of 2 or
      greater, and a urinary catheter. Among surgical patients, an American Society of
      Anesthesiologists (ASA) score of 2 or greater was associated with any type of NI
      (P = .03). Enterobacteriaceae were the most frequent cause of NI, followed by
      coagulase-negative staphylococci; viruses were rarely the cause. CONCLUSIONS:
      This national prevalence survey yielded valuable information about the rate and
      risk factors of pediatric NI. A new comorbidity score showed promising
      performance. ASA score may be a predictor of NI. The season in which a prevalence
      survey is conducted must be considered, as this determines whether seasonal viral
      infections are observed. Periodic prevalence surveys are a simple and cost
      effective method for assessing NI and comparing rates among pediatric hospitals.

PMID- 15484803
TI  - Healthcare-associated infections among neonates in Brazil.
AB  - OBJECTIVE: To describe the epidemiology of healthcare-associated infections
      (HAIs) among neonates. DESIGN: Prospective surveillance of HAIs was conducted
      during 2 years. Infections beginning within 48 hours of birth were defined as
      HAIs of maternal origin. Death occurring during an active episode of HAI was
      considered related to HAI. SETTING: Seven neonatal units located in three
      Brazilian cities. PATIENTS: All admitted neonates were included and observed
      until discharge. RESULTS: Twenty-two percent of 4,878 neonates had at least one
      HAI. The overall incidence density was 24.9 per 1,000 patient-days, and 28.1% of
      all HAIs were maternally acquired. HAI rates ranged from 12.3% in the group with
      a birth weight (BW) of more than 2,500 g to 51.9% in the group with a BW of 1,000
      g or less. The main HAIs were bloodstream infection (BSI) and pneumonia.
      Coagulase-negative staphylococci, Enterobacter species, Staphylococcus aureus,
      and Klebsiella pneumoniae were the main pathogens. Forty percent of all deaths
      were related to HAI. Central venous catheter (CVC)-associated BSIs per 1,000 CVC
      days ranged from 17.3 (BW, 1,501 to 2,500 g; device utilization [DU], 0.11) to
      34.9 (BW, < or = 1,000 g; DU, 34.92). Ventilator-associated pneumonia per 1,000
      ventilator-days ranged from 7.0 (BW, < or = 1,000 g; DU, 0.34) to 9.2 (BW, 1,001
      to 1,500 g; DU, 0.14). CONCLUSIONS: The high proportion of HAIs of maternal
      origin highlights perinatal care issues in Brazil and the need to improve the
      diagnosis of neonatal HAIs. The very low BW group and device-associated
      infections should be priorities for prevention strategies in this population.

PMID- 15484804
TI  - Transmission of methicillin-resistant Staphylococcus aureus to preterm infants
      through breast milk.
AB  - OBJECTIVE: To determine a potential source of MRSA colonization and infection
      among preterm infants in a neonatal intensive care unit (NICU) using molecular
      analysis of breast milk samples. DESIGN: Case report, outbreak investigation.
      RESULTS: Preterm triplets were delivered at 26 weeks' gestation via cesarean
      section when routine active surveillance for MRSA was performed for all infants
      in a NICU. Surveillance consisted of swabbing the throat, nose, and umbilicus
      (TNU) weekly. Although infants A and B initially had negative TNU swabs, repeat
      cultures were positive for MRSA on day of life (DOL) 10 and DOL 18, respectively.
      Surveillance and clinical cultures for infant C were negative. Infant A developed
      sepsis, and multiple blood cultures were positive for MRSA beginning on DOL 14.
      Infant B developed conjunctivitis and a conjunctival exudate culture was positive
      for MRSA on DOL 70. Both infants were fed breast milk via nasogastric tube.
      Cultures of breast milk samples for infants A and B dated prior to either
      infant's first positive surveillance culture were positive for MRSA. All MRSA
      isolates had identical results on antibiotic susceptibility testing. PFGE
      demonstrated identical banding patterns for the MRSA isolates from the blood
      culture of infant A, breast milk for infants A and B, and a surveillance swab
      from infant B. At no time did the mother develop evidence of mastitis or other
      local breast infection. CONCLUSIONS: MRSA can be passed from mother to preterm
      infant through contaminated breast milk, even in the absence of maternal
      infection. Colonization and clinical disease can result.

PMID- 15484805
TI  - Risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae in
      a neonatal intensive care unit.
AB  - Risk factors for colonization or infection with extended-spectrum beta-lactamase
      (ESBL)-producing Enterobacteriaceae during an outbreak in a neonatal intensive
      care unit (NICU) included low gestational age and exposure to third-generation
      cephalosporins. We also reviewed the existing medical literature regarding the
      clinical epidemiology of ESBLs in NICUs .

PMID- 15484806
TI  - Pediatric risk of mortality and hospital infection.
AB  - We studied the association of Pediatric Risk of Mortality scores with nosocomial
      infections among 341 critically ill patients admitted to a pediatric intensive
      care unit between June 1998 and December 2000. Through stepwise logistic
      regression analysis, the best predictors for nosocomial infections were device
      utilization ratio, antimicrobial therapy, and length of stay.

PMID- 15484807
TI  - Impact of surveillance rounds on adherence to infection control policies and
      procedures at a children's hospital.
AB  - Adherence to written infection control policies and procedures was studied and on
      site education was provided for 1 year at a children's hospital. There was
      significant improvement in sharp objects disposal, hazardous waste handling,
      availability of personal protective equipment, isolation precautions, and staff
      knowledge regarding location of the exposure control plan.

PMID- 15484808
TI  - Survey of tuberculin skin test positivity among Israeli pediatric hospital
      workers.
AB  - Tuberculin skin test (TST) was performed in 374 healthcare workers. TST results
      of induration of 10 mm or more and 20 mm or more were noted in 44.9% and 10.4%,
      respectively. Positive TST (> 10 mm) was found to be significantly associated
      with age, country of origin, and duration of employment.

PMID- 15484809
TI  - [Genomic diversity of Escherichia coli].

PMID- 15484810
TI  - [Pathogenicity and genome of Vibrio parahaemolyticus].

PMID- 15484811
TI  - [Internalization and intracellular replication of Brucella in macrophages].

PMID- 15484812
TI  - [Virulence of outer membrane proteins of periodontopathogenic bacteria].

PMID- 15484813
TI  - [Bacteria/host interaction mediated by Nod proteins].

PMID- 15484814
TI  - [Methodological consideration in studying the exocytosis mechanisms using
      microdialysis].
AB  - Microdialysis has become an effective and frequently used technique to study the
      extracellular levels of monoamine, i.e. dopamine, serotonin and norepinephrine in
      the central nervous system. However, the detailed exocytosis mechanisms of
      monoamine using microdialysis has remained to be clarified. The present report
      introduces methods for administration of voltage-sensitive calcium channel (VSCC)
      inhibitors and soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor (SNARE) inhibitors to clarify the mechanisms of monoamine exocytosis
      using in vivo microdialysis. The N-type and P-type VSCCs are inhibited by
      perfusion with omega-conotoxin GVIA and omega-agatoxin IVA, respectively;
      however, their diffusion rate from internal to external spaces of the
      microdialysis probe is lower than 1%. Unlike VSCC inhibitors, SNAP-25,
      synaptobrevin and syntaxin can be cleavaed with botulinum toxin type A, B and C,
      respectively. These toxins (with molecular weights over 500,000) bind
      specifically to the presynaptic membrane via the heavy chain, while the light
      chain enters the cytosol, where it displays zinc-endopeptidase activity directed
      to proteins of the neuroexocytosis apparatus. Therefore, to prevent SNARE
      activity, botulinum toxins are microinjected. These two methods, perfusion with
      VSCC inhibitors and microinjection with botulinum toxins, can contribute to the
      clarification of the mechanisms of monoaminergic exocytosis.

PMID- 15484815
TI  - [Microglial cell death induced by polyamines].
AB  - Pathological activation of microglia, which quiescently reside in physiological
      CNS, causes various neurodegenerative diseases. Endogenous polyamines, spermidine
      (SPD) and spermine (SPM) are known to be activators of cell proliferation and
      differentiation. We examined the effect of polyamines on microglial activation in
      culture. Cultured microglia prepared from the whole brains of newborn rats
      produced nitric oxide (NO) by the stimulation with lipopolysaccharide (LPS). LPS
      induced NO production was remarkably inhibited by SPD and SPM. Cell viability
      assessed by total mitochondrial activity decreased by the incubation with SPD and
      SPM for 24 h. In astrocyte culture, on the other hand, polyamines showed no
      significant effect on either LPS-induced NO production or cell viability. After
      the treatment with SPM for 24 h, the cells changed into small round shapes, and
      were markedly stained with propidium iodide. By the staining with Hoechst33342,
      condensation and fragmentation of the nucleus were often observed.
      Semiquantitative analysis of fragmented DNA with the ELISA technique revealed
      that a large amount of fragmented DNA appeared in cytosol prior to disruption of
      the cell membrane, suggesting that polyamines induced apoptosis. Fragmented DNA
      in cytosol increased dose dependently with SPM. These results suggest that
      particular polyamines induce cell death through apoptosis at low concentrations
      in cultured microglia

PMID- 15484816
TI  - [Specification of dorsal interneurons by Wnt signaling].
AB  - During development of the vertebrate central nervous system (CNS), highly
      proliferative cells in the ventricular zone of the neural tube serve themselves
      as progenitors of the various types of neurons, such as interneurons and motor
      neurons. In the dorsal half of the spinal cord, signals from the roof plate are
      required for the development of three classes of dorsal interneuron; D1, D2 and
      D3, listed from dorsal to ventral. This study demonstrates that mouse embryos
      lacking both Wnt-1 and Wnt-3a are indeed defective in determination of dorsal
      interneurons. Generation of D1 and D2 classes of dorsal interneurons is impaired;
      this loss of the dorsal interneurons is compensated by a dorsal expansion of D3
      interneuron populations. Most importantly, expression of BMP family proteins,
      which have been reported to be able to induce dorsal interneurons, is not
      significantly affected in these mutant embryos. Moreover, the induction of D1 and
      D2 class interneurons by Wnt-3a protein in the isolated medial region of chick
      neural plate is demonstrated. Together, these observations clearly indicate that
      Wnt signaling has a critical role in the generation of D1 and D2 dorsal
      interneurons.

PMID- 15484817
TI  - [Priming of neuronal differentiation of cultured neural stem cells by
      neutrophins].
AB  - Neurogenesis is promoted by basic helix-loop-helix (bHLH) transcription factors
      Mash1, Math1 and/or NeuroD but suppressed by another set, Hes1 and Hes5. It is
      still unknown what kinds of extracellular signals are involved in their
      regulation. Therefore, the effects of neurotrophins on the expression of bHLH
      factors and neuronal differentiation were investigated by the use of cultured
      mouse neural stem cells. Each neurotrophin increased Mash1 and Math1 mRNAs of the
      stem cells growing in the presence of fibroblast growth factor-2 (FGF-2), but did
      not alter Hes1, Hes5 or NeuroD mRNA levels. Simultaneously, most of the cells
      expressed nestin, but not microtubule-associated protein 2 (MAP2), and still
      remained undifferentiated. FGF-2 removal from the medium reduced the levels of
      Hes1 and Hes5 mRNAs and increased those of Mash1, Math1, and NeuroD mRNAs,
      resulting in substantial neuronal differentiation. However, when the cells were
      pretreated with a neurotrophin, brain-derived neurotrophic factor, FGF-2 removal
      enhanced earlier NeuroD expression and generated many more MAP2-positive cells.
      The high level of Mash1 and Math1 that had been elevated at FGF-2 withdrawal
      accelerated NeuroD expression in cooperation with the reduced Hes1 and Hes5
      expression. Our present results suggest that neurotrophins stimulate neuronal
      differentiation via altering the balance of expression of various bHLH
      transcription factors.

PMID- 15484818
TI  - [Roles of semaphorins in neuron network formation].
AB  - A secreted semaphorin, Sema3A, is an axon guidance molecule that induces collapse
      of growth cones and repels axons in vitro. Neuropilin-1 (Nrp-1) is a receptor for
      Sema3A. To clarify the function of the semaphorin in vivo, we generated Sema3A
      mutant mice and Nrp-1 mutant mice by targeted disruption of the Sema3A and Nrp-1
      genes, respectively. These mutant mouse embryos showed a severe defect in the
      trajectory and projection of PNS efferent, suggesting that the Nrp-1-mediated
      Sema3A signals play crucial roles in the directional guidance of nerve fibers and
      the establishment of PNS networks. The deprivation of Nrp-1-mediated Sema3A
      signals also induced disorganization of the sympathetic nervous system. In the
      Nrp-1 and Sema3A mutant mouse embryos, more than half of the TH-positive SG
      neurons were distributed at ectopic positions. As a whole, the sympathetic trunk
      was severely disorganized. Sema3 A recombinant proteins inhibited migration of
      the wild-type (Nrp-1-expressing) but not Nrp-1-deficient SG neurons in culture,
      suggesting that Nrp-1-mediated Sema3A inhibitory signals are essential in precise
      migration of SG neurons, as well as directional guidance of axons.

PMID- 15484819
TI  - [Molecular mechanisms for the development and aging of the primate central
      nervous system].
AB  - The central nervous system (CNS) of primates, including humans, is more complex
      than the CNS of other mammals. In particular, the cerebral cortex expands during
      evolution and this has resulted in the emergence of higher cognitive abilities in
      primates. Recent neurochemical and neuroanatomical methods have clarified the
      presence of various neuroactive substances including neuropeptides, neurotrophic
      factors and growth associated proteins in the developing mammalian cerebral
      cortex. Among these signal molecules, we have focused on somatostatin (SRIF),
      neurotrophins (BDNF, NT-4/5 and NT-3) and their receptors (Trk), growth
      associated proteins such as GAP-43 and SCG-10 during the development and aging of
      primate CNS. We found that although full-length TrkB, a high affinity receptor
      for BDNF and NT4/5, was detected from the embryonic stage to adulthood, the level
      of truncated TrkB which lacks tyrosine kinase domain, only increased after birth.
      This development of truncated TrkB correlated well with down-regulation in the
      gene expression of GAP-43 and SCG-10. The reductions of GAP-43 and SCG-10 may
      result in the elimination of callosal axons in the monkey cerebral cortex after
      birth. The highest levels of BDNF protein in the various cerebral cortices
      occurred between postnatal 1 and 6 when the number of synapses is highest. In
      contrast, there was no transient increase in the levels of NT4/5 or NT3 after
      birth. These findings suggest that BDNF is one of the candidates for the synaptic
      development of the primate cerebral cortex. During aging processes, we observed
      decreases in the levels of SRIF and BDNF mRNAs in the cerebral cortex. Since BDNF
      is an upstream gene expression molecule of SRIF, the decline of SRIF mRNA during
      aging may be due to the decrease in the gene expression of BDNF. Similar
      reductions of gene expressions of SRIF and BDNF in the brains of the patients
      with Alzheimer's disease, suggest that aged monkeys are good model animals for
      these neuro-degenerative diseases.

PMID- 15484820
TI  - [Signal transduction mechanisms for the survival and death of neurons and muscle
      cells: modulation by membrane lipid rafts and their abnormality in the disorders
      of the nervous system].
AB  - Recent advances have accumulated evidence that membrane lipid rafts or caveola
      play an essential role in cell-cell communications and signal transduction across
      membranes. The main constituents of lipid rafts include cholesterol,
      sphingomyelin, and glycosphingolipids such GM1 ganglioside. Many receptor-type
      tyrosine kinases and GPI-anchored proteins are now known to be the residents of
      lipid rafts. Therefore, it has been postulated that there are some direct or
      indirect interactions between these signaling molecules and lipids within lipid
      rafts, but no definite evidence has been available. In this study, we explored
      the molecular interactions of receptor-type tyrosine kinase, Trk, which essential
      for the neuronal survival and differentiation and for lipids, especially
      gangliosides. We also examined how the chemical depletion of another main lipid,
      cholesterol, affects the cellular function of muscle cells and its outcome. The
      data clearly indicate that 1) chemical and genetical depletion of gangliosides
      resulted in the impairment of the Trk-dependent protein kinase cascade. 2)
      depletion of intracellular cholesterol induced tyrosine phosphorylations of
      several cellular proteins including the p110 catalytic subunit of
      phosphatidylinositol-3 kinase and phospholipase C-gamma and the destruction of
      lipid rafts resulting in the development of apoptotic cell death of muscle cells.

PMID- 15484822
TI  - [Bridging the genomic approach and the neurodevelopmental and neurodenerative
      hypothesis of schizophrenia].
AB  - Schizophrenia is hypothesized as a neurodevelopmental and neurodegenerative
      disorder based on the following findings. 1. MRI studies have revealed brain
      structural abnormalities from the onset of schizophrenia and the progress of
      these structural abnormalities. 2. Histopathological studies have elucidated
      cytoarchitectural abnormalities in schizophrenic brains without gliosis. 3.
      Obstetric complications are one of the risk factors for schizophrenia. 4. Relapse
      of schizophrenia results in a deteriorating progress of the disorder.
      Furthermore, data from family, twin and adoption studies show evidence of a
      substantial genetic component in schizophrenia, Thus, a molecular genetic study
      combined with a neurodevelopmental and neurodegenerative hypothesis is required
      to elucidate the pathophysiology of schizophrenia. The positive association
      between neuregulin 1 and Icelandic schizophrenia that has been reproduced in
      Scottish and North European schizophrenia is one of the intriguing examples of
      this type of research. Neuregulin 1 regulates the cytoarchitecture of brain. Mice
      mutated for neuregulin 1 show a behavioral phenotype that overlaps with mouse
      models for schizophrenia. Furthermore, the behavioral phenotypes of the
      neuregulin 1 hypomorphs are reversible with clozapine. We also demonstrated a
      positive association between schizophrenia and a 5-HT5A receptor polymorphism,
      Pro15Ser, that may have role in cell differentiation in the brain.

PMID- 15484821
TI  - [Identification of novel PSD proteins and their possible functions].
AB  - There are a number of mRNA species localizing to dendrites of neuronal cells, and
      a postsynaptic local translation system may allow local and rapid synthesis of
      key postsynaptic proteins required for expression of synaptic plasticity. Most
      mRNAs localizing in the postsynaptic region may be translated into postsynaptic
      proteins, localizing in the postsynaptic subcompartments, such as PSD, the
      synaptic plasma membrane (SPM), or the cytoplasmic region of the spines or
      dendrites. However, there appears to be a number of dendritic mRNAs (Dems) and
      postsynaptic proteins still to be found. Recently, we developed a method to
      identify a large number of mRNA species associated with PSD fraction (Tian et al
      (1999) Mol Brain Res, 72: 147-157). During the identification process of these
      mRNAs, we cloned several full-length cDNAs, such as a synaptic short form LDL
      receptor-related protein (ssLRP) (Tian et al (2002) Soc Neurosci Abst, 28: 405),
      synaptic ubiquitin-specific protease (synUSP), TANC (a protein containing
      tetratricopeptide repeat [TPR], ankyrin repeat, and coiled-coil domain) (Suzuki
      et al (2003) Soc Neurosci Abst, 29), and so forth. In situ hybridization and
      immunochemical studies confirmed dendritic localization of mRNAs for these
      proteins in dendrites, and the localization of these proteins in postsynaptic
      regions, respectively. Some proteins contained signals for targeting the PSD and
      interacted with various PSD proteins. We present properties and possible
      physiological functions of these proteins and report the recent progress in our
      project to identify a large number of postsynaptic proteins based on the
      identification of dendritically localizing mRNAs.

PMID- 15484823
TI  - [Cortical plasticity revealed by functional neuroimaging].

PMID- 15484824
TI  - [Designed molecular probes in brain research: molecular imaging of IP2 receptor
      in the human brain].
AB  - The study of the role of prostaglandins in living human brain requires a highly
      designed non-invasive molecular probe with a specific function in the central
      nervous system and high stability in an in vivo system in addition to the ability
      of blood-brain-barrier penetration. We succeeded in designing 15R-TIC, which
      binds with a novel prostacyclin receptor subtype (IP2) expressed specifically in
      the central nervous system. 15R-TIC exhibited a distinct nerve-protecting effect
      in both high oxygen and in vivo ischemic conditions. In addition, a rapid C
      methylation reaction, developed in order to incorporate a short-lived 11C
      positron nuclide into the molecule, realized the synthesis of 15R-[11C]TIC methyl
      ester with the radioactivity of 2.5 GBq. The molecular imaging was established
      for both monkey and human brains by intravenous injection of this positron
      emission tomography (PET) probe.

PMID- 15484825
TI  - [Identification of the memory component that decays with age in Drosophila].
AB  - No one can escape from memory decay with advancing age. Understanding molecular
      mechanisms underlying age-related memory impairment (AMI) is important not only
      from the scientific viewpoint but also for elucidating novel targets that may
      eventually lead to developing therapeutics for combating memory loss. AMI had
      been generally considered to be an overall or nonspecific decay of memory
      processes that results from dysfunction of neural networks. However, behavioral
      genetic tests of this hypothesis have not been carried out. Using Drosophila, we
      have demonstrated the first extensive behavioral-genetic characterization of AMI.
      We discovered that AMI results from the specific decay of only one memory
      component, amnesiac-dependent middle-term memory, and not other components. In
      support of this finding, we show that memory in aged flies is identical to that
      of amnesiac mutants, and while other memory mutants show a further decrease in
      memory upon aging, amnesiac flies do not. These results provide the first
      identification of a specific gene pathway underlying AMI.

PMID- 15484826
TI  - [Molecular neurogenetics of sensory behaviors in the hematode C. elgans].
AB  - The molecular mechanisms of neural plasticity, learning and memory are still
      poorly understood. The nematode Caenorhabditis elegans is capable of responding
      to a variety of environmental changes through its nervous system, consisting of
      only 302 neurons. C. elegans is an ideal model organism to elucidate neural
      plasticity, learning and memory at molecular, cellular and neuronal network
      levels. Thermotaxis behavior is particularly amenable to dissect learning and
      memory at all these levels. After cultivation at a certain temperature with food,
      C. elegans migrates to the cultivation temperature on a temperature gradient. By
      contrast, cultivation in food-deprived condition induces cultivation temperature
      avoidance behavior on a temperature gradient. We have been conducting forward as
      well as reverse genetic approaches to identify molecules, neurons and neuronal
      networks that are responsible for aspects of learning and memory in thermotaxis
      behavior.

PMID- 15484827
TI  - [Functional analysis of acid sensing ion channels].
AB  - Acid-sensing ion channel-2a (ASIC2a) is a proton-gated cation channel, probably
      contributing to sour-taste detection in rat taste cells. We found the transcripts
      of ASIC2b in the circumvallate, foliate and fungiform papillae.
      Immunohistochemical analyses also revealed that ASIC2b, as well as ASIC2a, was
      expressed in a subpopulation of taste cells, and some of the cells displayed both
      ASIC2a and ASIC2b immunoreactivities. Coimmunoprecipitation studies with
      circumvallate papillae extracts indicated that ASIC2b associated with ASIC2a to
      form assemblies. Oocyte electrophysiology demonstrated that the ASIC2a/ASIC2b
      channel generated amiloride-insensitive currents at pH 2.0. These findings
      provide persuasive explanations for the amiloride insensitivity of acid-induced
      responses of rat taste cells. Acid-sensing ion channels (ASICs) also mediate acid
      induced nociception in mammals. In our psychophysical experiments, direct
      infusion of acidic solutions (pH > or = 6.0) into human skin caused localized
      pain, which was blocked by amiloride, an inhibitor of ASICs, but not by
      capsazepine, an inhibitor of TRPV1. Under more severe acidification (pH 5.0)
      amiloride was less effective in reducing acid-evoked pain. In addition,
      capsazepine had a partial blocking effect under these conditions. Amiloride
      itself did not block capsaicin-evoked localized pain. Our results suggest that
      ASICs (ASIC1a and ASIC3) are leading acid sensors in human nociceptors and that
      TRPV1 participates in the nociception mainly under extremely acidic conditions.

PMID- 15484828
TI  - [Synaptic development and abnormality at protein level].
AB  - A pyramidal neuron in the adult brain has numerous dendritic spines, which are
      typical postsynaptic structures. The shapes of spines are abnormal in the case of
      mental retardation, epilepsy, or Fragile X syndrome. Since the spine is thought
      to be a fundamental element in synaptic function, the abnormal shape of the spine
      is thought to be directly associated with brain dysfunction in the above
      diseases. Spine shape is regulated by each cytoskeletal protein. Over-expression
      of drebrin, a major actin-binding protein in the spine, elongates the spine. In
      the brain of Alzheimer's disease and Down syndrome, drebrin is greatly reduced.
      This indicates the structural abnormality of the spine as pathogenesis in the
      dementia. Now the spine morphogenesis comes into the spotlight. Although spines
      are thought to be formed from dendritic filopodia, the conversion mechanism of
      filopodia to spines has not been fully elucidated. We have recently demonstrated
      that cluster formation of drebrin-actin complex in filopodia is a key step for
      this conversion. When the cluster formation is inhibited, PSD-95 is not
      accumulated at postsynaptic sites. Since the drebrin-A isoform is necessary for
      the cluster formation, the regulation of drebrin A expression is now a focus in
      the field of spine formation.

PMID- 15484829
TI  - [Drug resistance in recurrent cases of tuberculosis].
AB  - PURPOSE: Investigate drug resistant rate in recurrent cases after cure, or after
      drop-out from treatment, and the analysis of the risk factors for acquired drug
      resistance in these cases. OBJECT: Patients who were previously treated for
      tuberculosis that was drug sensitive or unknown about previous drug sensitivity,
      and were hospitalized to Fukujuji Hospital to start treatment for recurrent
      tuberculosis from Jan. 1, 1993 to Dec. 31, 2003. Primary drug resistant cases
      were excluded and cases were further divided into full sensitive cases and cases
      with drug sensitivity test results were unknown. METHOD: Chart review. RESULT:
      Drug resistant rate (any resistance to INH, RFP, SM, EB) in all recurrent cases
      (N=200) was 16.5%. Availability of previous drug sensitivity results affected on
      the drug resistant rate in recurrent cases. In previously pan-sensitive cases,
      drug resistant rate was 4.3% and it was lower than the rate in primary treated
      cases. No significant risk factor for acquired drug resistance was not found,
      including poor adherence to medication. CONCLUSION: Every effort should be made
      to know the previous drug sensitivity results because these results have a major
      impact on drug resistance rate at recurrence. Doctor's mismanagements of
      tuberculosis patients might be the major factor for acquired drug resistance in
      recurrent cases, and it is needed for the improvement of tuberculosis control
      program to implement the measures to control these mismanagements.

PMID- 15484830
TI  - [Acute onset of somnolence and amnesia due to cerebral infarction of bilateral
      thalamus accompanied with tuberculous meningitis: a case report].
AB  - A 55-year-old man was admitted to our hospital because of somnolence and
      aspontaneity. He was hospitalized in the psychopathic ward under the initial
      diagnosis of depression. Chest X-ray showed infiltration in both upper lobe.
      Twelve days later, Mycobacterium tuberculosis was detected from his sputum and
      was confirmed by RT-PCR. Cerebrospinal fluid findings showed elevated ADA and
      mononuclear cells, suggesting the presence of tuberculous meningitis. However,
      the brain CT revealed no abnormal findings. By applying antituberculous treatment
      the pulmonary lesion improved but psychological symptoms remained. Three months
      later follow-up brain MRI was examined. Contrast enhanced granuloma was detected
      in the ambiens, suprasellar and quadrigeminal cisterns. A strong signal was seen
      in the left frontal thalamus and a weak enhanced lesion was detected in the right
      frontal thalamus on a T2 enhanced image. These lesions showed low intensity on a
      T1 enhanced image, suggesting cerebral infarction affecting the bilateral
      thalamus. Somnolence and memory disorder was due to cerebral infarction of the
      bilateral thalamus and tuberculous meningitis contributed to form the
      intracranial lesion. From the experience of this case, it is needed to consider
      cerebral infarction (especially the thalamus) due to tuberculous meningitis when
      we examine the patients with acute onset of psychological symptoms.

PMID- 15484831
TI  - [Pulmonary tuberculosis case with consistant findings of endobronchial spread in
      chest roentogenography for about three years: a case report].
AB  - We reported a case of pulmonary infection by Mycobacterium tuberculosis
      complicated by endobronchial spread. Chest roentogenography and CT for an 85-year
      old male complaining of cough showed endobronchial spread in right upper lung
      field. His sputum culture for eight weeks showed 10-20 colonies of Mycobacterium
      tuberculosis. Transbronchial lung biopsy revealed granulomas with caseous
      necrosis. Findings in chest XP and CT after the therapy with INH, RFP and EB for
      six months showed much improvement.

PMID- 15484832
TI  - [Tuberculosis in the elderly].
AB  - Recently, the proportion of the elderly in the newly registered TB patients has
      increased. Not only the relative increase, but the newly registered TB patients
      older than 70 years is leveling off, and the number of smear positive TB patients
      among the elderly is obviously on the increase. The rapid aging of the population
      and the blunting of the decreasing speed of the TB patients percentage in the
      elderly may be accountable for the increase in the elderly TB patients. Elderly
      TB patients often have complications. Particularly noticeable is the high
      percentage of complications by cardiovascular diseases, malignant tumor, central
      nervous diseases and digestive tract diseases. However, the proportion of
      complications by diabetes was higher in the non-elderly persons (younger than 64
      years). The frequency of pyrazinamide being used was extremely low in the
      elderly, particularly in the late cases of the elderly. In elderly TB patients,
      there were many cases of death and moving out, and the clinical results were
      poor. Of the female elderly TB patients, many were the late cases of the elderly
      and cases of moving out after discharge. Of the male elderly TB patients, there
      were many cases of death, which was conspicuous particularly in the late cases of
      the elderly. As the measures to counter the elderly TB patients who continue to
      increase in number, mention can be made of the early discovery of elderly TB
      patient, measures to prevent the development of TB in the elderly and support to
      hospital treatment of elderly TB patients. In the future, taking measures is
      needed so that the development of TB in the elderly be suppressed and that TB
      treatment of the elderly be carried out smoothly.

PMID- 15484833
TI  - An audit a day keeps the agency at bay: OIG's evolving view of hospital
      compliance programs (part 2).

PMID- 15484834
TI  - Crossing borders: drugs bought from Canada can save your money but may also risk
      your life. here's how to save both.

PMID- 15484835
TI  - Fake drugs, real worries: high prices and the Internet are making U.S. patients
      easy prey.

PMID- 15484836
TI  - Savings in the cards: picking the best Medicare drug discount card is tougher
      than ever.

PMID- 15484837
TI  - Shopping around: prices at nearby drugstores vary by huge amounts.

PMID- 15484838
TI  - Lessons from a first patient.

PMID- 15484839
TI  - The testing of America.

PMID- 15484840
TI  - Counsel's "reasonable investigation" of mental health evidence in capital
      litigation: implications for post-conviction proceedings.

PMID- 15484841
TI  - You are a moral compass for your practice.

PMID- 15484842
TI  - Fee schedule highlights include implementation of Medicare prescription drug
      bill.

PMID- 15484843
TI  - Expanding to cyberspace. What one practice learned in developing a web site for a
      large multispecialty group practice.

PMID- 15484844
TI  - Medical melting pot. Immigration rules for international physicians.

PMID- 15484845
TI  - The doings are in the details. Tracking productivity through detailed job
      descriptions.

PMID- 15484846
TI  - The proper care and feeding of administrators. How to bridge individual
      performance and organizational effectiveness? Start by caring for your
      professional self.
AB  - As many medical practice administrators focus on the proper care and feeding of
      their organizations, they've developed the same ailment as other "caregivers"-
      they tend to their own professional development and needs as an afterthought. But
      as any self-preserving caregiver can tell you, nurturing yourself actually helps
      those you serve. How should administrators balance and respond to their own goals
      and preferences and their organization's needs--while anticipating changes in the
      broader environment?

PMID- 15484847
TI  - Be sure to cover your REER: leader-manager models in health care integration of
      theory and practice.
AB  - Good daily management combines the prioritization tools of health care management
      with tested leadership visions that create a symbiosis for success. We introduce
      the concept of REER--revenues, expenses, efficiencies and risk--as daily
      benchmarks to guide managers and blend REER with other leadership premises. A
      complete REER model includes leadership elements that define the tools and when
      to use them. A vision for the business requires a broad spectrum of tools to
      succeed: integrity, persistence, energy, insight into people and the instinct to
      know when to focus on revenue and when to allocate for risk.

PMID- 15484848
TI  - Entity matters. Financial consequences of entity selection for the physician
      owned practice.
AB  - When a physician-owned medical practice selects a legal structure, it also opts
      for a set of tax attributes that can have a significant impact on operations and
      financial decision-making. Whether forming a new practice, contemplating a merger
      or simply dealing with the tax and operational issues of their current situation,
      practice executives and physician owners need to understand the tax and financial
      implications of the different entities.

PMID- 15484849
TI  - [Cataloging of medical publications today].

PMID- 15484851
TI  - [ABO blood groups and haemolytic disease of newborns--population-genetic
      analysis].
AB  - Classical works dealing with the possibility of mother-child incompatibility with
      regard to basic ABO blood groups give contradictory conclusions (e.g.--Matsunaga
      et al. 1962, Thompson et al. 1991). Bioreproductive and population-genetic
      indicators have been studied in a sample of live births and in two pregnancy
      samples characterised by different "a priori" and "a posteriori" risk assessment.
      The analysis points out that ABO blood groups can influence fertility of
      different parental pairs, with a possible impact on the assessment of the
      individual pregnancy risc.

PMID- 15484850
TI  - [The effect of acetylcholine, dopamine, histamine and serotonin in the tracheal
      smooth muscle in the response with desquamative and non-desquamative epithelium
      of respiratory pathways in vitro].
AB  - In this paper we have examined the receptor bronchial system in newly born
      children with desquamative and with preserved epithelium of aerial pathways. The
      response was followed in: acetylcholine, dopamine, histamine and scrotonin in
      various concentrations (10(-4), 10(-3), 10(-2), 10(-1)). The tonus of the
      tracheal smooth muscle was examined in 29 tracheal preparations, taken by autopsy
      after excitation from various factors. On the basis of functional investigation
      it has been established as follows: acetylcholine had caused the response of the
      bronchial smooth muscle with desquamative epithelium in a significant way (p <
      0.01), in contrast to cases which were treated with unimpaired epithelium (p >
      0.1). The effect of dopamine was significant in cases with desquamative
      epithelium (p < 0.05), in contrast to cases where epithelium was preserved (p >
      0.1). The effect of histamine was also significant in cases with desquamative
      epithelium of respiratory pathways (p < 0.01), in contrast to cases where
      epithelium was preserved. Cases with desquamative epithelium in serotonin have
      reacted significantly (p < 0.01), despite cases which had no impaired epithelium
      of respiratory pathways (p > 0.1). Obtained results show that the response of the
      tracheal discs with desquamative epithelium of respiratory pathways was
      significant (p < 0.01), despite cases which had preserved the epithelium of
      respiratory pathways (p > 0.1). This suggest that various mediators with local
      effect are released during desquamation of epithelium which increase thus the
      bronchial reactibility of respiratory pathways.

PMID- 15484852
TI  - [Detection of Chlamydia trachomatis in cervical smear samples with determined
      HPV].
AB  - OBJECTIVE: Chlamydia trachomatis (CT) causes infertility, ectopyc pregnancy,
      pelvic inflammatory disease (PID) and conjunctivitis. Human Papilloma Virus (HPV)
      is a virus with broad spectrum effects. This particularly refers to HPV of high
      oncogenic potential (HPV - HR) because of its participation in cervical
      oncogenesis. The authors wanted to determine correlation between cervical HPV
      infection and detection of CT taken from female patient's smear of different
      levels of cervical intraepithelial neoplasm (CIN I - III) and ASCUS (Atypical
      Squamous Cells of Uncertain Significance) modifications. METHODS: Cytological
      analysis was used for 94 cervical samples--Papanicolaou method. The samples were
      presented in accordance with valid Bethesda Classification. The samples were
      treated by HPV DNA assay (Digene Hybrid Capture II). RESULTS: Out of 64 HPV
      positive samples, detected CT was found in 24 (37.5%) samples. Out of 50 HPV
      positive group samples with high degree risk ( HPV - HR), 18 (36%) contained CT.
      Frequency of CT was registered in ASCUS modifications in 55.6%, CIN I 16.7%, CIN
      II 16.7% and CIN III 11.0% samples. We found 3 (10.0%) of detected CT in HPV
      negative control group. CONCLUSION: Research results showed correlation between
      HPV cervical infection and CT. The higher the level of cell dedifferentiation
      (ASCUS CIN I - III) is, the higher number of cervical infections with CT is.

PMID- 15484853
TI  - [Dysfunction of the left chamber after myocardial infarct].
AB  - Dysfunction of the left chamber of the heart happens when the function is not
      sufficient to supply all organs with needed quantity of blood, oxygen and
      nourishing materials. Consequence is an exhaustion of the heart compensatory and
      peripheral mechanisms. The research is based on the results of the analysis of
      residual changes that remained since acute myocardium infarct got over (scar,
      contracture changes, conductivity) and analysis of the remained functional part
      of the left chamber myocardium. Electrocardiogram, echocardiography and exercise
      test were used. 60 patients were examined. 6 varieties of chronic myocardium
      infarcts were found: anteroseptal, inferior, anterolateral and anterior-broaden,
      high-lateral and posterior localisation. Wagner's method QRS-scoring system and
      scores for wall motion by the American of ehocardiography were found the damage
      size of the myocardium mass. Correlative coefficient is full (r = 1.0). In chi2
      test there is no significant difference (Wagner, echocardiography) in dimensions
      of old infarct (p < 0.05). Dyastolic dysfunction was set by echocardiographic
      method for 75%, systolic 41.11% examinees, remodelling in 80%, extended
      isovolumetric relaxation time and time of deceleration in 100% cases, speed ratio
      E-wave and A-wave below 1.0 in 82.66% cases. Exercise test was made for 85%
      examinees. Dysfunction was registered in 84.37%, diastolic in 80.39%, systolic in
      43.17% cases. On the base of coronarographie results (23.33% examinees) the
      sensitivity was set for: exercise test in systolic dysfunction is 42.86%, in
      dyastolic is 71.43% and echocardiography in systolic disfunction is 57.14%, in
      dyastolic 100%. According to echocardiographic analysis of parameters the
      greatest influence has reduction of ejection fraction with 36.67% in systolic and
      extension of the period of deceleration with 38.79% in diastolic dysfunction.
      There is a good complement of the tested methods (p < 0.05). There is
      possibility, with these methods to appraise dysfunction of the left chamber in
      old myocardium infarct with conclusion that echocardiography is more sensitive
      since gives more data and direct visualization of changes.

PMID- 15484854
TI  - [Correlation of preoperative and postoperative functional status of the liver in
      hepatic resection].
AB  - Preoperative liver function have singificant influence on the morbidity and
      mortality, by performing liver resections. In addition to, intraoperative factors
      may contribute appearance, undesirable postoperative complications. Functional
      parameters, which we analized in this study (ALT, AST, albumins, bilirubin and
      prothrombin time), was measured preoperative and in the postoperative course.
      Study include 60 patients which are divided in two groups, at the basis Child
      Pugh score, for the estimate operative risks. Results showes that, after liver
      resections frequently complications were in the group of patients with impaired
      liver functions, specially if the extensivity resections of the liver parenchyma,
      was the greatest.

PMID- 15484855
TI  - [Analysis of doxazosin efficacy in the treatment of the benign prostatic
      enlargement].
AB  - OBJECTIVE: to analyze doxazosin efficacy in the treatment of patients with proved
      benign prostatic enlargement (BPE), according to the reduction of the level of
      symptoms and urodynamic obstruction as well as reduction in detrusor contraction
      duration (DCD). SAMPLE AND METHODOLOGY: 31 BPE patients after fulfilling
      International Prostatic Symptom score, undergone complete urodynamic measurement
      (uroflowmetry, cystometry and pressure/flow studies). All methodology of
      urodynamic measurement and definitions were based on the definitions of the
      International Continence Society. Three months therapy with doxazosin (4 mg
      daily) was prescribed to each patient, and the same control examinations were
      done after the treatment with analysis of all relevant data. RESULTS: A reduction
      of the symptoms (T-paired test) (I-PSS from average of 12.6 decreased to 6.2; p <
      0.0001), has been noticed, improvement of quality of life (from average 2.5
      decreased to 1.5; p < 0.0001), as well as increasing of the maximal flow (average
      Q(max) grew for 1.9 ml/sec; p < 0.05). URA dropped from 39,6 cmH2O to 34,1 cmH2O
      (p < 0.01), remaining in the obstructive region, although 32% of the patients
      experienced absolute reduction of obstruction (URA < 29 cmH2O). The most
      prominent result was a drastic reduction in the duration of the detrusor
      contraction (average DCD from 105 sec. dropped to average 73.4 sec. with p <
      0.0001). Other urodynamic parameters, as well as post void residual urine, were
      not changed significantly. Than patients were allocated in the two groups based
      on the pre treatment detrusor contraction duration with cut-off point of 90 sec.
      and the post treatment characteristics were examined (Wilcoxon test). Both groups
      were shown reduction regarding I-PSS, (its irritative and obstructive domain),
      but reduction of 54% for DCD > 90 sec group is better than for the 46% for the
      other group. Further, there is a difference among groups regarding several
      important characteristics. DCD > 90 sec. group showed increasing in urinary flow
      for 21% (p < 0.05), decreasing of URA for 13% (p < 0.05), improvement in the
      quality of life for the 46% (p < 0.001) as well as reduction in DCD for 32% (p <
      0.001), what was not shown in the pretreatment DCD < 90 sec. group. CONCLUSION:
      Doxazosin is a potent reducer of the symptoms in the treatment of the BPE,
      enhancing urinary flow and reducing DCD in the first place. Albeit, possibility
      of urodynamic obstruction reduction and influence to the volume of post void
      residual urine is limited, thus doxazosin is recommended to the patient with
      moderate obstruction, prolonged detrusor contraction duration and moderate levels
      of the symptoms. Patients with pretreatment prolonged DCD will be better
      responders to the therapy. This finding implicates necessity ofurodynamic
      measurements before treatment in order to optimize therapeutic effect of drug for
      individual patient.

PMID- 15484856
TI  - [Complications in anterior eye segment after Nd-YAG laser capsulotomy].
AB  - This study was to examine the frequency of complications in the anterior eye
      segment, following the Nd-YAG laser posterior capsulotomy. Next objective was to
      examine the influence of pulse energy to the appearance of complications. Most
      often we registered increase in eye pressure in the first hour following the
      intervention.

PMID- 15484857
TI  - [Detection of antibodies against cytomegalovirus in donors and recipients of
      kidney transplants].
AB  - The paper analyzed the values and titer of IgM and IgG antibodies on CMV in
      donors and recipients of kidney transplntats. The objective was to investigate
      the presence of CMV in donors and recipients. SUBJECT AND METHODS: Test enzignost
      anti CMV/IgM was used. Detection of antibodies in 15 donors before
      transplantation and in 22 patients-recipients before and after the
      transplantation was done. RESULTS: From total of 15 donors, the values of IgM
      ranged from 0,002 I.U. do 0,080 I.U. One case was positive. Four patients were
      seropositive and treated by Gancyclovirom 10 mg/kg/b.w (body weight) in period of
      3 month. IgM values ranged from 0.88399 to 25978. The control finding 3 patients
      was negative, in 1 patient positive (IgM 0.569). In 18 patients the finding was
      negative. Refererent value for IgM is < 0.10 the result is negative. For IgG four
      times greater value comparing to the basic value was found. CONCLUSION: The most
      significant factor for reactivation of CMV infection is iatrogenic
      Immunosuppressive therapy. Exclusion of CMV infection in donors and negative
      finding in recipient decrease.

PMID- 15484858
TI  - [Prognostic significance of juvenile chronic arthritis onset types].
AB  - Juvenile chronic arthritis (JCA) is a disease or a group of diseases with chronic
      nonsuportive connective tissue inflammation. Depending of the onset of the
      disease and its course in the first six months there are three major types:
      systemic, poliyarticular and pauciarticular disease. Indicators of bad prognosis
      were: systemic form with signs of inflammation in the first six months,
      poliarticular onset and course, RF positivity, positive ANA and eye involvement.
      In the period from 1996 to 2002 at the Cardiology-Rheumatology Department in
      Sarajevo Pediatric Clinic 63 patients were addmited. Out of this 49 (78%) were
      new cases JCA was more frequent among school age girls 35 (57%). Systemic--onset
      JCA 9 patients (14%), polyarticular onset 19 patients (30%), pauciarticular onset
      35 (55%). 15 (23.8%) was RF (rheumatoid factor) negative, 4 (6.3%) RF positive.
      Pauciarticular forms type 1 were 20 (31.7%), type II were 15 (23.8%). In 11
      (17.5%) patients laboratory tests and clinical signs indicated poor prognosis.
      All patients with indicators of poor prognosis needed more aggressive therapy.
      Although JCA is the most frequent rheumatic disease and the leading cause of
      invalidity, and one of the most frequent chronic disease in children, we still do
      not know enough. The optimal treatment is still a challenge especially onset of
      JCA with poor prognosis.

PMID- 15484859
TI  - [Respiratory risk factors in development of postoperative complications after
      lung resection].
AB  - The objectives of the study were to identify possible associated respiratory risk
      factors and to assess incidence of overall postoperative complications after lung
      resection. We reviewed 110 patients undergoing lung resections because of
      malignant neoplasms or benign lung diseases. The risk of postoperative
      complications was evaluated using unuvariate analysis. Results confirmed that low
      FEV1, postoperative high PaCO2, ASA-status and advanced age were factors
      associated with development of postoperative complications.

PMID- 15484860
TI  - [Treatment of migraine].
AB  - The epidemiological parameters of the migraene headaches with the occurrence in
      the most productive life age with the subjective intensive experience of the
      characteristic pain in migraene headaches are the reason of interest for migraene
      as the headache "sui generis" from the pathological and therapeutic aspect. The
      diagnosis of migraene is put according the criteria for migraene headaches. In
      persons who suffer from migraene it is certainly, that besides the family
      anamnesis and the solalled precipiting factors there are also the tresh hold for
      migraene attack to which the basic change in serotonin generator in the brain
      branch. In the therapeutic approach are used the profilacted and therapeutic
      measures. The agents which act as agonists 5-HT 1 receptors have simptomatic
      effects in migraena, while antagonists of 5-HT 2 recetors are-successful in the
      prophilaxis. Selective agonist 5-HT 1 receptor is sumatrypane and has broken the
      more year sterotipy in the treatment of the migraene, while the more recent
      agonists receptors 5-HT 1D alfa and 5-HT D1berta receptor rizatriptan,
      zolmitriptan, naratriptan show clearly the therapeutic aim of the treatment or
      migraene influence on the serotoenergic generator of the brain branch and the
      consecutive change of the cerebral circulation.

PMID- 15484861
TI  - [Follow-up of the structure of patients treated at the Out-patient Department for
      Clinical Psychotherapy and Psychosomatic Disorders at the Psychiatric Clinic in
      Sarajevo].
AB  - Researches in the field of psychiatric disorders epidemilogy have shown that
      difference in the psychiatric morbidity between males and females exists within
      the categories of non-psychotic disorders. Findings of numerous researches
      regarding use of the various forms of community mental health services indicated
      that females are more present in the out-patient and in-patient community mental
      health treatment, as well as their higher number in community mental health
      treatment. Research which has been done in 2002 at the Department for Clinical
      Psychotherapy and Psychosomatic Disorders at the Psychiatric Clinic in Sarajevo,
      which has been focused on years 1990, 1993, 2000 has, for peacefull 1990, shown
      identical results comparing with the findings of similar studies which have been
      conducted in USA and Wester Europe countries. War and psychotraumatization caused
      by war, especially for the male population, led to changes in psychiatric
      morbidity structure, as well as in the structure of services which were realized
      by male and female patients. War effects in all examined parameters, especially
      on male patients, are visible continiously including even the last examined year,
      2002, that is the seventh post-war year.

PMID- 15484863
TI  - [Unusual therapeutic approach in treatment of pulmonary tuberculosis in six year
      old girl].
AB  - We report about interesting case of treatment of pulmonary tuberculosis in 6-year
      old girl. Antituberculotic therapy induced toxic hepatitis (rise of
      transaminases, indirect hiperbilirubinemia). She was treated with streptomycin,
      etambutol, ciprofloxacyn and systemic corticosteroides. Two gallbladder stones
      and high-density sediment were diagnosed after ultrasound examination which could
      be a side effect of the therapy or previous findings.

PMID- 15484862
TI  - Psychic disorders in former prisoners of war.
AB  - AIM: To analyze the kind and the representation of psychic disorders in former
      prisoners of war and war veterans who were not detained in camps. METHODS: The
      analyzed sample consisted of 160 respondents divided into two groups. A group of
      100 former prisoners of war and a group of 60 war veterans who had not been
      detained in camps. All the respondents are males and were psychically in healthy
      condition prior to the war. The modified Harvard Trauma Questionnaire was used to
      diagnose traumatic experience, and a questionnaire according to the DSM IV
      criteria was used to diagnose posttraumatic stress disorder. The Depressiveness
      Scale D-92 was used to diagnose depressiveness; the questionnaire STAI was used
      to diagnose anxiety; CAGE Questionnaire was used to diagnose alcoholism. RESULTS:
      The former prisoners of war had traumatic experience at a higher level as
      compared to the war veterans who had not been detained in camps (P < 0.05). The
      symptoms of PTSD were manifested by 55% of camp inmates as compared to 33.3% of
      war veterans (P < 0.05). Depressive disorder was diagnosed in 52% of camp inmates
      and 31.7% of war veterans (P < 0.05). No statistically significant difference was
      found among the analyzed groups relating to anxiety and alcohol drinking.
      CONCLUSIONS: The former prisoners of war were living through a severer stage and
      had a more sundry traumatic experience. Severer stage of traumatic experience
      conditioned statistically higher representation of psychic disorders (PTSD and
      depressiveness) in the former prisoners of war as compared to the war veterans.

PMID- 15484864
TI  - [Drug abuse as social-medical problem].
AB  - Drug abuse in the region of Sarajevo is in the worrying increase. It is not only
      about the increase of number of the dependents and death cases because of the
      overdosage, lowering of the age limit of the dependents to younger age groups and
      similar, but also about the absence of the severe long-term senseful and
      efficient collection of society in the solving of this problem. The aim of the
      research was to examine the attitudes and practice connected for abuse of drug in
      Sarajevo region. In connection with this was questionnaired 987 young people:
      students, middle age pupils of the eighth classes. We had also the controlled
      group of the examinees selected according the system of accidental sample (102).
      Also were performed the interviews with the experts for this problem: to
      psychologists, doctors, paedagogists, social workers, teachers, including also
      one number of the earlier and present dependents.

PMID- 15484865
TI  - [Infant walkers: the prevalence of use].
AB  - Infant walkers are mobile wheeled seats that allow infants to move around with
      their feet on the floor. They enable precocious locomotion in very young,
      otherwise prelocomotor infants. Prelocomotor walker experience prevents visual
      access to the moving limbs. Infant walker use can be associated with delay in
      achievement of normal locomotor milestones. Besides delayed motor development,
      contractures of the calf muscles and motor development mimicking spastic
      diparesis may appear. In the case of infant walker's use for the infants at risk
      for development of cerebral palsy, multiple side effects can be produced: the
      persistence of positive support reflex, heel cord contractures, subluxation and
      dislocation of the hips or pronation contractures of the upper extremities. The
      use of infant walkers increases the risk of injuries. The study has enrolled 150
      children and their mothers, from three big cities in Bosnia and Herzegovina
      (Sarajevo, Bihac, Zenica). All relevant data have been collected through the
      questionnaires. 130 children (86.6%) have used infant walkers. The mean age when
      the use of infant walker has started was 7 months. The mean time of daily use of
      infant walker was 1 hour 49 minutes. Twenty three children had various motor
      disturbances, 13 out of them (56.5%) have used infant walker. The mild injuries
      caused by using the infant walkers have been registered in 17 cases (11.3%). 83
      mothers (55.3%) were aware of infant walker's nocuous effects. CONCLUSION: The
      use of infant walkers has been spread widely under our circumstances. There is
      significant discrepancy between mothers' knowledge about nocuous effects of
      infant walkers and their practice. The use of infant walkers for infants with
      motor disturbances is especially harmful. The main reason for using infant
      walker, despite of its harmfulness, was mother's preoccupation with everyday
      household activities. It is necessary to engage health professionals to support
      antiwalker campaign (warning labels on the infant walkers, public education
      programs, etc). We recommend safer alternatives for child daycare, like
      stationary activity centers (so called "fenced play gardens".

PMID- 15484866
TI  - [One hundred thirty years of organizing health care system in Tuzla region].
AB  - The organized health care in Tuzla region begins by the establishment of
      hastahana in Tuzla 1874 year, when thanks the first graduated physician Dr.
      Mehmed Serbic Sami was opened the Vakuf's hospital in Tuzla, which he success
      fully lead to his death 1918 year. The great role in the treatment of the become
      ill inhabitants played the general hosptals, established during Australia
      Hungarian period (Tuzla - 1886, Brcko - 1886...) whose capacities later were
      enlarged, and their health staff enabled at the universitets in the surrounding
      countries, later also in B&H, during the past period. The significant role in
      this played also the series of the health educators from which some will become
      the names in the segment of the health-care in this region and wider. About them
      and the institutions in this region, which merited not to be overlet to for
      fulness, the authors write in this paper.

PMID- 15484868
TI  - Transitive responding in hooded crows requires linearly ordered stimuli.
AB  - Eight crows were taught to discriminate overlapping pairs of visual stimuli (A+ B
      , B+ C-, C+ D-, and D+ E-). For 4 birds, the stimuli were colored cards with a
      circle of the same color on the reverse side whose diameter decreased from A to E
      (ordered feedback group). These circles were made available for comparison to
      potentially help the crows order the stimuli along a physical dimension. For the
      other 4 birds, the circles corresponding to the colored cards had the same
      diameter (constant feedback group). In later testing, a novel choice pair (BD)
      was presented. Reinforcement history involving stimuli B and D was controlled so
      that the reinforcement/nonreinforcement ratios for the latter would be greater
      than for the former. If, during the BD test, the crows chose between stimuli
      according to these reinforcement/nonreinforcement ratios, then they should prefer
      D; if they chose according to the diameter of the feedback stimuli, then they
      should prefer B. In the ordered feedback group, the crows strongly preferred B
      over D; in the constant feedback group, the crows' choice did not differ
      significantly from chance. These results, plus simulations using associative
      models, suggest that the orderability of the postchoice feedback stimuli is
      important for crows' transitive responding.

PMID- 15484869
TI  - Within-session delay-of-reinforcement gradients.
AB  - Within-session delay-of-reinforcement gradients were generated with pigeons by
      progressively increasing delays to reinforcement within each session. In
      Experiment 1, the effects of imposing progressive delays on variable-interval and
      fixed-interval schedules were investigated while controlling for simultaneous
      decreases in reinforcer rate across the session via a within-subject yoked
      control procedure. Rate of key pecking decreased as a negatively decelerated
      function of delay of reinforcement within a session. These rate decreases were
      greater than those during a yoked-interval session in which the rate of immediate
      reinforcement decreased at the same rate as it did under the progressive-delay
      procedure. In Experiment 2, delay-of-reinforcement gradients were shallower when
      the progressive delay intervals were signaled by a blackout than when they were
      unsignaled. The delay gradients obtained in each experiment were similar to those
      generated under conditions in which different delays of reinforcement are imposed
      across blocks of sessions. The present procedure offers a technique for rapidly
      generating delay-of-reinforcement gradients that might serve as baselines for
      assessing the effects of other behavioral and pharmacological variables.

PMID- 15484870
TI  - Effects of GABA modulators on the repeated acquisition of response sequences in
      squirrel monkeys.
AB  - The present study investigated the effects of positive and negative GABA(A)
      modulators under three different baselines of repeated acquisition in squirrel
      monkeys in which the monkeys acquired a three-response sequence on three keys
      under a second-order fixed-ratio (FR) schedule of food reinforcement. In two of
      these baselines, the second-order FR schedule and the discriminative stimuli for
      the response sequence were manipulated ("chain-strained" and "tandem-strained").
      In the third baseline condition, response-independent tail shock was presented
      during acquisition of the response sequence. All of these baselines maintained
      high error levels and produced slow rates of acquisition. Under both the chain
      strained and tandem-strained conditions, the positive GABA(A) modulator triazolam
      (0.0032-0.1 mg/kg) and the negative GABA(A) modulators beta-CCE (ethyl-beta
      carboline-3-carboxylate; 0.01-1 mg/kg), beta-CCM (methyl-beta-carboline-3
      carboxylate; 0.0032-0.1 mg/kg), and FG-7142 (methyl-beta-carboline-3-carboxamide;
      0.18-10 mg/kg) dose-dependently decreased overall response rate compared to
      administration of saline (control). Under the same two conditions, triazolam and
      the negative GABA(A) modulators also increased the percentage of errors; however,
      the effects on accuracy frequently depended on the baseline condition and the
      particular modulator. In contrast, triazolam only decreased errors and enhanced
      acquisition in the presence of concurrent response-independent tail shock when
      compared to saline administration under this condition. The neutral GABA(A)
      modulator, flumazenil (1 mg/kg), had no effect on rate or accuracy of responding
      when administered alone, but antagonized the rate-decreasing and error-increasing
      effects produced by the negative GABA(A) modulators. Together, these data suggest
      that the effects of both the positive and negative GABAA modulators on
      acquisition can be similar in squirrel monkeys (i.e., both types of modulator may
      produce rate-decreasing and error-increasing effects) and that their effects on
      acquisition depend, in part, on the environmental conditions maintaining
      acquisition.

PMID- 15484871
TI  - Signal-detection analyses of conditional discrimination and delayed matching-to
      sample performance.
AB  - Quantitative analyses of stimulus control and reinforcer control in conditional
      discriminations and delayed matching-to-sample procedures often encounter a
      problem; it is not clear how to analyze data when subjects have not made errors.
      The present article examines two common methods for overcoming this problem.
      Monte Carlo simulations of performance demonstrated that both methods introduced
      systematic deviations into the results, and that there were genuine risks of
      drawing misleading conclusions concerning behavioral models of signal detection
      and animal short-term memory.

PMID- 15484872
TI  - Correlated inhibitory and excitatory inputs to the coincidence detector:
      analytical solution.
AB  - We present a solution for the steady-state output rate of an ideal coincidence
      detector receiving an arbitrary number of excitatory and inhibitory inputspike
      trains. All excitatory spike trains have identical binomial count distributions
      (which includes Poisson statistics as a special case) and arbitrary pairwise
      cross correlations between them. The same applies to the inhibitory inputs, and
      the rates and correlation functions of excitatory and inhibitory populations may
      be the same or different from each other. Thus, for each population
      independently, the correlation may range from complete independence to perfect
      correlation (identical processes). We find that inhibition, if made sufficiently
      strong, will result in an inverted U-shaped curve for the output rate of a
      coincidence detector as a function of input rates for the case of identical
      inhibitory and excitory input rates. This leads to the prediction that higher
      presynaptic (input) rates may lead to lower postsynaptic (output) rates where the
      output rate may fall faster than the inverse of the input rate, and shows some
      qualitative similarities to the case of purely excitatory inputs with synaptic
      depression. In general, we find that including inhibition invariably and
      significantly increases the behavioral repertoire of the coincidence detector
      over the case of pure excitatory input.

PMID- 15484873
TI  - An instance of coincidence detection architecture relying on temporal coding.
AB  - Although time and space are interrelated in every occurrence of real-world
      events, only spatial codes are used at the basic level of most computational
      architectures. Inspired by neurobiological facts and hypotheses that assign a
      primordial coding role to the temporal dimension, and developed to address both
      cognitive and engineering applications, guided propagation networks (GPNs) are
      aimed at a generic real-time machine, based on time-space coincidence testing.
      The involved temporal parameters are gradually introduced, in relation with
      complementary applications in the field of human-machine communication: sensori
      motor modeling, pattern recognition and natural language processing.

PMID- 15484874
TI  - A network of coincidence detector neurons with periodic and chaotic dynamics.
AB  - We propose a simple neural network model to understand the dynamics of temporal
      pulse coding. The model is composed of coincidence-detector neurons with uniform
      synaptic efficacies and random pulse propagation delays. We also assume a global
      negative feedback mechanism which controls the network activity, leading to a
      fixed number of neurons firing within a certain time window. Due to this
      constraint, the network state becomes well defined and the dynamics equivalent to
      a piecewise nonlinear map. Numerical simulations of the model indicate that the
      latency of neuronal firing is crucial to the global network dynamics; when the
      timing of postsynaptic firing is less sensitive to perturbations in timing of
      presynaptic spikes, the network dynamics become stable and periodic, whereas
      increased sensitivity leads to instability and chaotic dynamics. Furthermore, we
      introduce a learning rule which decreases the Lyapunov exponent of an attractor
      and enlarges the basin of attraction.

PMID- 15484875
TI  - Dynamics and the single spike.
AB  - Responses of vestibular primary afferent neurons to head rotation exhibit
      fractional-order dynamics. As a consequence, the head tends to be in a localized
      region of its state-space at spike times of a particular neuron during arbitrary
      head movements, and single spikes can be interpreted as state measurements. We
      are developing a model of neural computations underlying trajectory prediction
      and control tasks, based on this experimental observation. This is a step toward
      a formal neural calculus in which single spikes are modeled realistically as the
      operands of neural computation.

PMID- 15484876
TI  - On the sample complexity of learning for networks of spiking neurons with
      nonlinear synaptic interactions.
AB  - We study networks of spiking neurons that use the timing of pulses to encode
      information. Nonlinear interactions model the spatial groupings of synapses on
      the neural dendrites and describe the computations performed at local branches.
      Within a theoretical framework of learning we analyze the question of how many
      training examples these networks must receive to be able to generalize well.
      Bounds for this sample complexity of learning can be obtained in terms of a
      combinatorial parameter known as the pseudodimension. This dimension
      characterizes the computational richness of a neural network and is given in
      terms of the number of network parameters. Two types of feedforward architectures
      are considered: constant-depth networks and networks of unconstrained depth. We
      derive asymptotically tight bounds for each of these network types. Constant
      depth networks are shown to have an almost linear pseudodimension, whereas the
      pseudodimension of general networks is quadratic. Networks of spiking neurons
      that use temporal coding are becoming increasingly more important in practical
      tasks such as computer vision, speech recognition, and motor control. The
      question of how well these networks generalize from a given set of training
      examples is a central issue for their successful application as adaptive systems.
      The results show that, although coding and computation in these networks is quite
      different and in many cases more powerful, their generalization capabilities are
      at least as good as those of traditional neural network models.

PMID- 15484877
TI  - Dynamic proximity of spatio-temporal sequences.
AB  - Recurrent networks can generate spatio-temporal neural sequences of very large
      cycles, having an apparent random behavior. Nonetheless a proximity measure
      between these sequences may be defined through comparison of the synaptic weight
      matrices that generate them. Following the dynamic neural filter (DNF) formalism
      we demonstrate this concept by comparing teacher and student recurrent networks
      of binary neurons. We show that large sequences, providing a training set well
      exceeding the Cover limit, allow for good determination of the synaptic matrices.
      Alternatively, assuming the matrices to be known, very fast determination of the
      biases can be achieved. Thus, a spatio-temporal sequence may be regarded as
      spatio-temporal encoding of the bias vector. We introduce a linear support vector
      machine (SVM) variant of the DNF in order to specify an optimal weight matrix.
      This approach allows us to deal with noise. Spatio-temporal sequences generated
      by different DNFs with the same number of neurons may be compared by calculating
      correlations of the synaptic matrices of the reconstructed DNFs. Other types of
      spatio-temporal sequences need the introduction of hidden neurons, and/or the use
      of a kernel variant of the SVM approach. The latter is being defined as a
      recurrent support vector network (RSVN).

PMID- 15484878
TI  - An analysis of globally connected active rotators with excitatory and inhibitory
      connections having different time constants using the nonlinear Fokker-Planck
      equations.
AB  - The globally connected active rotators with excitatory and inhibitory connections
      having different time constants under noise are analyzed using the nonlinear
      Fokker-Planck equation, and their oscillatory phenomena are investigated. Based
      on numerically calculated bifurcation diagrams, both periodic solutions and
      chaotic solutions are found. The periodic firings are classified based on the
      firing period, the coefficient of variation, and the correlation coefficient, and
      weakly synchronized periodic firings which are often observed in physiological
      experiments are found.

PMID- 15484881
TI  - Different types of signal coupling in the visual cortex related to neural
      mechanisms of associative processing and perception.
AB  - The hypothesis of object representation by synchronization in the visual cortex
      has been supported by our recent experiments in monkeys. They demonstrated local
      synchrony among gamma activities (30-90 Hz) and their perceptual modulation,
      according to the rules of figure-ground segregation. However, gamma-synchrony in
      primary visual cortex is restricted to few mm, challenging the synchronization
      hypothesis for larger cortical object representations. The restriction is due to
      randomly changing phase relations among locally synchronized patches which,
      however, form continuous waves of gamma-activity, traveling across object
      representations. The phase continuity of these waves may support coding of object
      continuity. Interactions across still larger distances, measured among cortical
      areas in human data, involve amplitude envelopes of gamma signals. Based on
      models with spiking neurons we discuss potentially underlying mechanisms. Most
      important for gamma synchronization are local facilitatory connections with
      distance-dependent delays. They also explain the occurrence of gamma waves and
      the restriction of gamma-synchrony. Fast local feedback inhibition generates
      gamma oscillations and supports local synchrony, while slow shunting inhibitory
      feedback supports figure-ground segregation. Finally, dispersion in inter-areal
      far projections destroys coherence of gamma signals, but preserves their
      amplitude modulations. In conclusion, we propose that the hypothesis of
      associative processing by gamma synchronization be extended to more general forms
      of signal coupling.

PMID- 15484882
TI  - Dynamical analysis of neural oscillators in an olfactory cortex model.
AB  - This paper presents a theoretical approach to understand the basic dynamics of a
      hierarchical and realistic computational model of the olfactory system proposed
      by W. J. Freeman. While the system's parameter space could be scanned to obtain
      the desired dynamical behavior, our approach exploits the hierarchical
      organization and focuses on understanding the simplest building block of this
      highly connected network. Based on bifurcation analysis, we obtain analytical
      solutions of how to control the qualitative behavior of a reduced KII set taking
      into consideration both the internal coupling coefficients and the external
      stimulus. This also provides useful insights for investigating higher level
      structures that are composed of the same basic structure. Experimental results
      are presented to verify our theoretical analysis.

PMID- 15484883
TI  - Which model to use for cortical spiking neurons?
AB  - We discuss the biological plausibility and computational efficiency of some of
      the most useful models of spiking and bursting neurons. We compare their
      applicability to large-scale simulations of cortical neural networks.

PMID- 15484884
TI  - The role of temporal parameters in a thalamocortical model of analogy.
AB  - How multiple specialized cortical areas in the brain interact with each other to
      give rise to an integrated behavior is a largely unanswered question. This paper
      proposes that such an integration can be understood under the framework of
      analogy and that part of the thalamus and the thalamic reticular nucleus (TRN)
      may be playing a key role in this respect. The proposed thalamocortical model of
      analogy heavily depends on a diverse set of temporal parameters including axonal
      delay and membrane time constant, each of which is critical for the proper
      functioning of the model. The model requires a specific set of conditions derived
      from the need of the model to process analogies. Computational results with a
      network of integrate and fire (IF) neurons suggest that these conditions are
      indeed necessary, and furthermore, data found in the experimental literature also
      support these conditions. The model suggests that there is a very good reason for
      each temporal parameter in the thalamocortical network having a particular value,
      and that to understand the integrated behavior of the brain, we need to study
      these parameters simultaneously, not separately.

PMID- 15484885
TI  - Stimulus-specific oscillations in a retinal model.
AB  - High-frequency oscillatory potentials (HFOPs) in the vertebrate retina are
      stimulus specific. The phases of HFOPs recorded at any given retinal location
      drift randomly over time, but regions activated by the same stimulus tend to
      remain phase locked with approximately zero lag, whereas regions activated by
      spatially separate stimuli are typically uncorrelated. Based on retinal anatomy,
      we previously postulated that HFOPs are mediated by feedback from a class of axon
      bearing amacrine cells that receive excitation from neighboring ganglion cells
      via gap junctions-and make inhibitory synapses back onto the surrounding ganglion
      cells. Using a computer model, we show here that such circuitry can account for
      the stimulus specificity of HFOPs in response to both high- and low-contrast
      features. Phase locking between pairs of model ganglion cells did not depend
      critically on their separation distance, but on whether the applied stimulus
      created a continuous path between them. The degree of phase locking between
      spatially separate stimuli was reduced by lateral inhibition, which created a
      buffer zone around strongly activated regions. Stimulating the inhibited region
      between spatially separate stimuli increased their degree of phase locking
      proportionately. Our results suggest several experimental strategies for testing
      the hypothesis that stimulus-specific HFOPs arise from axon-mediated feedback in
      the inner retina.

PMID- 15484886
TI  - Theta-modulated feedforward network generates rate and phase coded firing in the
      entorhino-hippocampal system.
AB  - Principal cells of the hippocampus and of its only cortical input region, the
      entorhinal cortex exhibit place specific activity in the freely moving rat. While
      entorhinal cells have widely tuned place fields, hippocampal place fields are
      more localized and determine not only the rate but also the timing of place cell
      spikes. Several models have successfully attempted to explain this fine tuning
      making use of intrahippocampal attractor network dynamics provided by the
      recurrent collaterals of hippocampal area CA3. Recent experimental evidence shows
      that CA1 place cells preserve their tuning curves even in the absence of input
      from CA3. We propose a model in which entorhinal and hippocampal pyramidal cell
      populations are only connected via feedforward connections. Synaptic transmission
      in our sytem is gated by a class of interneurons inhibiting specifically the
      entorhino-hippocampal pathway. Theta rhythm modulates the activity of each
      component. Our results show that rhythmic shunting inhibition endows entorhinal
      cells with a novel type of temporal code conveyed by the phase jitter of
      individual spikes. This converts coarsely tuned place-specific activity in the
      entorhinal cortex to velocity-dependent postsynaptic excitation and, thus,
      provides hippocampal place cells with an input that has recently been proposed to
      account for their rate and phase coded firing. Hippocampal place fields are
      generated through this mechanism and also shown to be robust against variations
      in the level of tonic inhibition.

PMID- 15484887
TI  - Temporal codes and computations for sensory representation and scene analysis.
AB  - This paper considers a space of possible temporal codes, surveys
      neurophysiological and psychological evidence for their use in nervous systems,
      and presents examples of neural timing networks that operate in the time-domain.
      Sensory qualities can be encoded temporally by means of two broad strategies:
      stimulus-driven temporal correlations (phase-locking) and stimulus-triggering of
      endogenous temporal response patterns. Evidence for stimulus-related spike timing
      patterns exists in nearly every sensory modality, and such information can be
      potentially utilized for representation of stimulus qualities, localization of
      sources, and perceptual grouping. Multiple strategies for temporal (time,
      frequency, and code-division) multiplexing of information for transmission and
      grouping are outlined. Using delays and multiplications (coincidences), neural
      timing networks perform time-domain signal processing operations to compare,
      extract and separate temporal patterns. Separation of synthetic double vowels by
      a recurrent neural timing network is used to illustrate how coherences in
      temporal fine structure can be exploited to build up and separate periodic
      signals with different fundamentals. Timing nets constitute a time-domain scene
      analysis strategy based on temporal pattern invariance rather than feature-based
      labeling, segregation and binding of channels. Further potential implications of
      temporal codes and computations for new kinds of neural networks are explored.

PMID- 15484889
TI  - Robust sound onset detection using leaky integrate-and-fire neurons with
      depressing synapses.
AB  - A biologically inspired technique for detecting onsets in sound is presented.
      Outputs from a cochlea-like filter are spike coded, in a way similar to the
      auditory nerve (AN). These AN-like spikes are presented to a leaky integrate-and
      fire neuron through a depressing synapse. Onsets are detected with essentially
      zero latency relative to these AN spikes. Onset detection results for a tone
      burst, musical sounds and the DARPA/NIST TIMIT speech corpus are presented.

PMID- 15484891
TI  - A computational model of auditory selective attention.
AB  - The human auditory system is able to separate acoustic mixtures in order to
      create a perceptual description of each sound source. It has been proposed that
      this is achieved by an auditory scene analysis (ASA) in which a mixture of sounds
      is parsed to give a number of perceptual streams, each of which describes a
      single sound source. It is widely assumed that ASA is a precursor of attentional
      mechanisms, which select a stream for attentional focus. However, recent studies
      suggest that attention plays a key role in the formation of auditory streams.
      Motivated by these findings, this paper presents a conceptual framework for
      auditory selective attention in which the formation of groups and streams is
      heavily influenced by conscious and subconscious attention. This framework is
      implemented as a computational model comprising a network of neural oscillators,
      which perform stream segregation on the basis of oscillatory correlation. Within
      the network, attentional interest is modeled as a Gaussian distribution in
      frequency. This determines the connection weights between oscillators and the
      attentional process, which is modeled as an attentional leaky integrator (ALI).
      Acoustic features are held to be the subject of attention if their oscillatory
      activity coincides temporally with a peak in the ALI activity. The output of the
      model is an "attentional stream," which encodes the frequency bands in the
      attentional focus at each epoch. The model successfully simulates a range of
      psychophysical phenomena.

PMID- 15484892
TI  - Coding static natural images using spiking event times: do neurons cooperate?
AB  - To understand possible strategies of temporal spike coding in the central nervous
      system, we study functional neuromimetic models of visual processing for static
      images. We will first present the retinal model which was introduced by Van
      Rullen and Thorpe and which represents the multiscale contrast values of the
      image using an orthonormal wavelet transform. These analog values activate a set
      of spiking neurons which each fire once to produce an asynchronous wave of
      spikes. According to this model, the image may be progressively reconstructed
      from this spike wave thanks to regularities in the statistics of the coefficients
      determined with natural images. Here, we study mathematically how the quality of
      information transmission carried by this temporal representation varies over
      time. In particular, we study how these regularities can be used to optimize
      information transmission by using a form of temporal cooperation of neurons to
      code analog values. The original model used wavelet transforms that are close to
      orthogonal. However, the selectivity of realistic neurons overlap, and we propose
      an extension of the previous model by adding a spatial cooperation between
      filters. This model extends the previous scheme for arbitrary--and possibly
      nonorthogonal--representations of features in the images. In particular, we
      compared the performance of increasingly over-complete representations in the
      retina. Results show that this algorithm provides an efficient spike coding
      strategy for low-level visual processing which may adapt to the complexity of the
      visual input.

PMID- 15484894
TI  - Pulse-coupled neural networks for contour and motion matchings.
AB  - Two neural networks based on temporal coding are proposed in this paper to
      perform contour and motion matchings. Both of the proposed networks are three
      dimensional (3-D) pulse-coupled neural networks (PCNNs). They are composed of
      simplified Eckhorn neurons and mimic the structure of the primary visual cortex.
      The PCNN for contour matching can segment from the background the object with a
      particular contour, which has been stored as prior knowledge and controls the
      network activity in the form of spike series; The PCNN for motion matching not
      only detects the motion in the visual field, but also extracts the object moving
      in an arbitrarily specified direction. The basic idea of these two models is to
      encode information into the timing of spikes and later to decode this information
      through coincidence detectors and synapse delays to realize the knowledge
      controlled object matchings. The simulation results demonstrate that the temporal
      coding and the decoding mechanisms are powerful enough to perform the contour and
      motion matchings.

PMID- 15484896
TI  - Storage capacity diverges with synaptic efficiency in an associative memory model
      with synaptic delay and pruning.
AB  - It is known that storage capacity per synapse increases by synaptic pruning in
      the case of a correlation-type associative memory model. However, the storage
      capacity of the entire network then decreases. To overcome this difficulty, we
      propose decreasing the connectivity while keeping the total number of synapses
      constant by introducing delayed synapses. In this paper, a discrete synchronous
      type model with both delayed synapses and their prunings is discussed as a
      concrete example of the proposal. First, we explain the Yanai-Kim theory by
      employing statistical neurodynamics. This theory involves macrodynamical
      equations for the dynamics of a network with serial delay elements. Next,
      considering the translational symmetry of the explained equations, we rederive
      macroscopic steady-state equations of the model by using the discrete Fourier
      transformation. The storage capacities are analyzed quantitatively. Furthermore,
      two types of synaptic prunings are treated analytically: random pruning and
      systematic pruning. As a result, it becomes clear that in both prunings, the
      storage capacity increases as the length of delay increases and the connectivity
      of the synapses decreases when the total number of synapses is constant.
      Moreover, an interesting fact becomes clear: the storage capacity asymptotically
      approaches 2/pi due to random pruning. In contrast, the storage capacity diverges
      in proportion to the logarithm of the length of delay by systematic pruning and
      the proportion constant is 4/pi. These results theoretically support the
      significance of pruning following an overgrowth of synapses in the brain and may
      suggest that the brain prefers to store dynamic attractors such as sequences and
      limit cycles rather than equilibrium states.

PMID- 15484899
TI  - Temporal processing in primate motor control: relation between cortical and EMG
      activity.
AB  - We investigated spatio-temporal information processing in the primate motor
      system. Corticomotoneuronal (CM) cells provide monosynaptic excitatory
      connections from motor cortex to spinal motoneurons and contribute causally to
      the time-varying electromyogram (EMG) of their target muscle. A multilayer
      perceptron (MLP) was used to evaluate the transfer function between neural
      activity of single CM cells and their target muscle EMG, using data from in-vivo
      recordings in primate motor cortex. For an optimal MLP performance, i.e., minimal
      error between recorded target EMG and MLP-derived EMG, the CM cell input period
      had to span the latency observed between CM cell peak activity and EMG peak
      activity. We argue that the same spike train may code two types of information:
      1) rate coding within the input window accounted for large-amplitude variations
      in the EMG signal and 2) temporal coding within a window of 40 ms just prior to
      the EMG output signal accounted for EMG variations of small amplitude. The
      transfer function of the MLP, thus, combines rate and temporal coding and
      suggests that CM cell output may also combine these two forms of coding. We
      predict that mutual constraints of rate and temporal coding would, however, would
      limit the CM output to code for particular temporal profiles of EMG, possibly
      adapted to bio-mechanical constraints.

PMID- 15484900
TI  - Signal processing with temporal sequences in olfactory systems.
AB  - The olfactory system is a very efficient biological setup capable of odor
      information processing with neural signals. The nature of neural signals
      restricts the information representation to multidimensional temporal sequences
      of spikes. The information is contained in the interspike intervals within each
      individual neural signal and interspike intervals between multiple signals. A
      mechanism of interactions between random excitations evoked by odorants in the
      olfactory receptors of the epithelium and deterministic operation of the
      olfactory bulb is proposed in this paper. Inverse Frobenius-Perron models of the
      bulb's temporal sequences are fitted to the interspike distributions of
      temporally modulated receptor signals. Ultimately, such pattern matching results
      in ability to recognize odors and offer a hypothetic model for signal processing
      occurring in the primary stage of the olfactory system.

PMID- 15484902
TI  - Synchrony detection and amplification by silicon neurons with STDP synapses.
AB  - Spike-timing dependent synaptic plasticity (STDP) is a form of plasticity driven
      by precise spike-timing differences between presynaptic and postsynaptic spikes.
      Thus, the learning rules underlying STDP are suitable for learning neuronal
      temporal phenomena such as spike-timing synchrony. It is well known that weight
      independent STDP creates unstable learning processes resulting in balanced
      bimodal weight distributions. In this paper, we present a neuromorphic analog
      very large scale integration (VLSI) circuit that contains a feedforward network
      of silicon neurons with STDP synapses. The learning rule implemented can be tuned
      to have a moderate level of weight dependence. This helps stabilise the learning
      process and still generates binary weight distributions. From on-chip learning
      experiments we show that the chip can detect and amplify hierarchical spike
      timing synchrony structures embedded in noisy spike trains. The weight
      distributions of the network emerging from learning are bimodal.

PMID- 15484903
TI  - Temporal coding in a silicon network of integrate-and-fire neurons.
AB  - Spatio-temporal processing of spike trains by neuronal networks depends on a
      variety of mechanisms distributed across synapses, dendrites, and somata. In
      natural systems, the spike trains and the processing mechanisms cohere though
      their common physical instantiation. This coherence is lost when the natural
      system is encoded for simulation on a general purpose computer. By contrast,
      analog VLSI circuits are, like neurons, inherently related by their real-time
      physics, and so, could provide a useful substrate for exploring neuronlike event
      based processing. Here, we describe a hybrid analog-digital VLSI chip comprising
      a set of integrate-and-fire neurons and short-term dynamical synapses that can be
      configured into simple network architectures with some properties of neocortical
      neuronal circuits. We show that, despite considerable fabrication variance in the
      properties of individual neurons, the chip offers a viable substrate for
      exploring real-time spike-based processing in networks of neurons.

PMID- 15484905
TI  - Hardware implementation of fuzzy Petri net as a controller.
AB  - The paper presents a new approach to fuzzy Petri net (FPN) and its hardware
      implementation. The authors' motivation is as follows. Complex industrial
      processes can be often decomposed into many parallelly working subprocesses,
      which can, in turn, be modeled using Petri nets. If all the process variables (or
      events) are assumed to be two-valued signals, then it is possible to obtain a
      hardware or software control device, which works according to the algorithm
      described by conventional Petri net. However, the values of real signals are
      contained in some bounded interval and can be interpreted as events which are not
      only true or false, but rather true in some degree from the interval [0, 1]. Such
      a natural interpretation from multivalued logic (fuzzy logic) point of view,
      concerns sensor outputs, control signals, time expiration, etc. It leads to the
      idea of FPN as a controller, which one can rather simply obtain, and which would
      be able to process both analog, and binary signals. In the paper both graphical,
      and algebraic representations of the proposed FPN are given. The conditions under
      which transitions can be fired are described. The algebraic description of the
      net and a theorem which enables computation of new marking in the net, based on
      current marking, are formulated. Hardware implementation of the FPN, which uses
      fuzzy JK flip-flops and fuzzy gates, are proposed. An example illustrating
      usefulness of the proposed FPN for control algorithm description and its
      synthesis as a controller device for the concrete production process are
      presented.

PMID- 15484906
TI  - Incremental multiple objective genetic algorithms.
AB  - This paper presents a new genetic algorithm approach to multiobjective
      optimization problems--incremental multiple objective genetic algorithms (IMOGA).
      Different from conventional MOGA methods, it takes each objective into
      consideration incrementally. The whole evolution is divided into as many phases
      as the number of objectives, and one more objective is considered in each phase.
      Each phase is composed of two stages. First, an independent population is evolved
      to optimize one specific objective. Second, the better-performing individuals
      from the single-objecive population evolved in the above stage and the
      multiobjective population evolved in the last phase are joined together by the
      operation of integration. The resulting population then becomes an initial
      multiobjective population, to which a multiobjective evolution based on the
      incremented objective set is applied. The experiment results show that, in most
      problems, the performance of IMOGA is better than that of three other MOGAs, NSGA
      II, SPEA, and PAES. IMOGA can find more solutions during the same time span, and
      the quality of solutions is better.

PMID- 15484907
TI  - Characterization of palmprints by wavelet signatures via directional context
      modeling.
AB  - The palmprint is one of the most reliable physiological characteristics that can
      be used to distinguish between individuals. Current palmprint-based systems are
      more user friendly, more cost effective, and require fewer data signatures than
      traditional fingerprint-based identification systems. The principal lines and
      wrinkles captured in a low-resolution palmprint image provide more than enough
      information to uniquely identify an individual. This paper presents a palmprint
      identification scheme that characterizes a palmprint using a set of statistical
      signatures. The palmprint is first transformed into the wavelet domain, and the
      directional context of each wavelet subband is defined and computed in order to
      collect the predominant coefficients of its principal lines and wrinkles. A set
      of statistical signatures, which includes gravity center, density, spatial
      dispersivity and energy, is then defined to characterize the palmprint with the
      selected directional context values. A classification and identification scheme
      based on these signatures is subsequently developed. This scheme exploits the
      features of principal lines and prominent wrinkles sufficiently and achieves
      satisfactory results. Compared with the line-segments-matching or interesting
      points-matching based palmprint verification schemes, the proposed scheme uses a
      much smaller amount of data signatures. It also provides a convenient
      classification strategy and more accurate identification.

PMID- 15484908
TI  - Direct adaptive iterative learning control of nonlinear systems using an output
      recurrent fuzzy neural network.
AB  - In this paper, a direct adaptive iterative learning control (DAILC) based on a
      new output-recurrent fuzzy neural network (ORFNN) is presented for a class of
      repeatable nonlinear systems with unknown nonlinearities and variable initial
      resetting errors. In order to overcome the design difficulty due to initial state
      errors at the beginning of each iteration, a concept of time-varying boundary
      layer is employed to construct an error equation. The learning controller is then
      designed by using the given ORFNN to approximate an optimal equivalent
      controller. Some auxiliary control components are applied to eliminate
      approximation error and ensure learning convergence. Since the optimal ORFNN
      parameters for a best approximation are generally unavailable, an adaptive
      algorithm with projection mechanism is derived to update all the consequent,
      premise, and recurrent parameters during iteration processes. Only one network is
      required to design the ORFNN-based DAILC and the plant nonlinearities, especially
      the nonlinear input gain, are allowed to be totally unknown. Based on a Lyapunov
      like analysis, we show that all adjustable parameters and internal signals remain
      bounded for all iterations. Furthermore, the norm of state tracking error vector
      will asymptotically converge to a tunable residual set as iteration goes to
      infinity. Finally, iterative learning control of two nonlinear systems, inverted
      pendulum system and Chua's chaotic circuit, are performed to verify the tracking
      performance of the proposed learning scheme.

PMID- 15484909
TI  - Approaching the Ocean Color problem using fuzzy rules.
AB  - In this paper, we propose a fuzzy logic-based approach which exploits remotely
      sensed multispectral measurements of the reflected sunlight to estimate the
      concentration of optically active constituents of the sea water. The relation
      between the concentrations of interest and the subsurface reflectances is modeled
      by a set of fuzzy rules extracted automatically from the data through a two-step
      procedure. First, a compact initial rule base is generated by projecting onto the
      input variables the clusters produced by a fuzzy clustering algorithm. Then, a
      genetic algorithm is applied to optimize the rules. Appropriate constraints
      maintain the semantic properties of the initial model during the genetic
      evolution. Results of the application of the fuzzy model obtained from data
      simulated with an ocean color model over the channels of the Medium Resolution
      Imaging Spectrometer are shown and discussed.

PMID- 15484910
TI  - Mental imagery for a conversational robot.
AB  - To build robots that engage in fluid face-to-face spoken conversations with
      people, robots must have ways to connect what they say to what they see. A
      critical aspect of how language connects to vision is that language encodes
      points of view. The meaning of my left and your left differs due to an implied
      shift of visual perspective. The connection of language to vision also relies on
      object permanence. We can talk about things that are not in view. For a robot to
      participate in situated spoken dialog, it must have the capacity to imagine
      shifts of perspective, and it must maintain object permanence. We present a set
      of representations and procedures that enable a robotic manipulator to maintain a
      "mental model" of its physical environment by coupling active vision to physical
      simulation. Within this model, "imagined" views can be generated from arbitrary
      perspectives, providing the basis for situated language comprehension and
      production. An initial application of mental imagery for spatial language
      understanding for an interactive robot is described.

PMID- 15484911
TI  - Enhancing prototype reduction schemes with recursion: a method applicable for
      "large" data sets.
AB  - Most of the prototype reduction schemes (PRS), which have been reported in the
      literature, process the data in its entirety to yield a subset of prototypes that
      are useful in nearest-neighbor-like classification. Foremost among these are the
      prototypes for nearest neighbor classifiers, the vector quantization technique,
      and the support vector machines. These methods suffer from a major disadvantage,
      namely, that of the excessive computational burden encountered by processing all
      the data. In this paper, we suggest a recursive and computationally superior
      mechanism referred to as adaptive recursive partitioning (ARP)_PRS. Rather than
      process all the data using a PRS, we propose that the data be recursively
      subdivided into smaller subsets. This recursive subdivision can be arbitrary, and
      need not utilize any underlying clustering philosophy. The advantage of ARP_PRS
      is that the PRS processes subsets of data points that effectively sample the
      entire space to yield smaller subsets of prototypes. These prototypes are then,
      in turn, gathered and processed by the PRS to yield more refined prototypes. In
      this manner, prototypes which are in the interior of the Voronoi spaces, and thus
      ineffective in the classification, are eliminated at the subsequent invocations
      of the PRS. We are unaware of any PRS that employs such a recursive philosophy.
      Although we marginally forfeit accuracy in return for computational efficiency,
      our experimental results demonstrate that the proposed recursive mechanism yields
      classification comparable to the best reported prototype condensation schemes
      reported to-date. Indeed, this is true for both artificial data sets and for
      samples involving real-life data sets. The results especially demonstrate that a
      fair computational advantage can be obtained by using such a recursive strategy
      for "large" data sets, such as those involved in data mining and text
      categorization applications.

PMID- 15484912
TI  - Providing QoS through machine-learning-driven adaptive multimedia applications.
AB  - We investigate the optimization of the quality of service (QoS) offered by real
      time multimedia adaptive applications through machine learning algorithms. These
      applications are able to adapt in real time their internal settings (i.e., video
      sizes, audio and video codecs, among others) to the unpredictably changing
      capacity of the network. Traditional adaptive applications just select a set of
      settings to consume less than the available bandwidth. We propose a novel
      approach in which the selected set of settings is the one which offers a better
      user-perceived QoS among all those combinations which satisfy the bandwidth
      restrictions. We use a genetic algorithm to decide when to trigger the adaptation
      process depending on the network conditions (i.e., loss-rate, jitter, etc.).
      Additionally, the selection of the new set of settings is done according to a set
      of rules which model the user-perceived QoS. These rules are learned using the
      SLIPPER rule induction algorithm over a set of examples extracted from scores
      provided by real users. We will demonstrate that the proposed approach guarantees
      a good user-perceived QoS even when the network conditions are constantly
      changing.

PMID- 15484913
TI  - Articulated pose identification with sparse point features.
AB  - We propose a general algorithm for identifying an arbitrary pose of an
      articulated subject with sparse point features. The algorithm aims to identify a
      one-to-one correspondence between a model point-set and an observed point-set
      taken from freeform motion of the articulated subject. We avoid common
      assumptions such as pose similarity or small motions with respect to the model,
      and assume no prior knowledge from which to infer an initial or partial
      correspondence between the two point-sets. The algorithm integrates local segment
      based correspondences under a set of affine transformations, and a global
      hierarchical search strategy. Experimental results, based on synthetic pose and
      real-world human motion data demonstrate the ability of the algorithm to perform
      the identification task. Reliability is increasingly compromised with increasing
      data noise and segmental distortion, but the algorithm can tolerate moderate
      levels. This work contributes to establishing a crucial self-initializing
      identification in model-based point-feature tracking for articulated motion.

PMID- 15484914
TI  - Intelligent automated control of life support systems using proportional
      representations.
AB  - Effective automatic control of Advanced Life Support Systems (ALSS) is a crucial
      component of space exploration. An ALSS is a coupled dynamical system which can
      be extremely sensitive and difficult to predict. As a result, such systems can be
      difficult to control using deliberative and deterministic methods. We investigate
      the performance of two machine learning algorithms, a genetic algorithm (GA) and
      a stochastic hill-climber (SH), on the problem of learning how to control an
      ALSS, and compare the impact of two different types of problem representations on
      the performance of both algorithms. We perform experiments on three ALSS
      optimization problems using five strategies with multiple variations of a
      proportional representation for a total of 120 experiments. Results indicate that
      although a proportional representation can effectively boost GA performance, it
      does not necessarily have the same effect on other algorithms such as SH. Results
      also support previous conclusions that multivector control strategies are an
      effective method for control of coupled dynamical systems.

PMID- 15484915
TI  - Modeling admissible behavior using event signals.
AB  - We describe here how to obtain a model for the admissible behavior of a discrete
      event system that is represented by a safe Petri net (PN) model. The transitions
      of this PN model may be controllable or uncontrollable. Also given is a
      sequential specification which is modeled with a special state machine. Then,
      using the condition and event arcs of net condition/event systems, a combined
      model of plant and specification is obtained. We use only the structure of this
      combined model to develop a method which gives the admissible behavior of the
      system. Thus, we avoid the complexity of a complete state enumeration.

PMID- 15484916
TI  - Facial action recognition for facial expression analysis from static face images.
AB  - Automatic recognition of facial gestures (i.e., facial muscle activity) is
      rapidly becoming an area of intense interest in the research field of machine
      vision. In this paper, we present an automated system that we developed to
      recognize facial gestures in static, frontal- and/or profile-view color face
      images. A multidetector approach to facial feature localization is utilized to
      spatially sample the profile contour and the contours of the facial components
      such as the eyes and the mouth. From the extracted contours of the facial
      features, we extract ten profile-contour fiducial points and 19 fiducial points
      of the contours of the facial components. Based on these, 32 individual facial
      muscle actions (AUs) occurring alone or in combination are recognized using rule
      based reasoning. With each scored AU, the utilized algorithm associates a factor
      denoting the certainty with which the pertinent AU has been scored. A recognition
      rate of 86% is achieved.

PMID- 15484917
TI  - Dynamical optimal training for interval type-2 fuzzy neural network (T2FNN).
AB  - Type-2 fuzzy logic system (FLS) cascaded with neural network, type-2 fuzzy neural
      network (T2FNN), is presented in this paper to handle uncertainty with dynamical
      optimal learning. A T2FNN consists of a type-2 fuzzy linguistic process as the
      antecedent part, and the two-layer interval neural network as the consequent
      part. A general T2FNN is computational-intensive due to the complexity of type 2
      to type 1 reduction. Therefore, the interval T2FNN is adopted in this paper to
      simplify the computational process. The dynamical optimal training algorithm for
      the two-layer consequent part of interval T2FNN is first developed. The stable
      and optimal left and right learning rates for the interval neural network, in the
      sense of maximum error reduction, can be derived for each iteration in the
      training process (back propagation). It can also be shown both learning rates
      cannot be both negative. Further, due to variation of the initial MF parameters,
      i.e., the spread level of uncertain means or deviations of interval Gaussian MFs,
      the performance of back propagation training process may be affected. To achieve
      better total performance, a genetic algorithm (GA) is designed to search optimal
      spread rate for uncertain means and optimal learning for the antecedent part.
      Several examples are fully illustrated. Excellent results are obtained for the
      truck backing-up control and the identification of nonlinear system, which yield
      more improved performance than those using type-1 FNN.

PMID- 15484918
TI  - Online tuning of fuzzy inference systems using dynamic fuzzy Q-learning.
AB  - This paper presents a dynamic fuzzy Q-learning (DFQL) method that is capable of
      tuning fuzzy inference systems (FIS) online. A novel online self-organizing
      learning algorithm is developed so that structure and parameters identification
      are accomplished automatically and simultaneously based only on Q-learning. Self
      organizing fuzzy inference is introduced to calculate actions and Q-functions so
      as to enable us to deal with continuous-valued states and actions. Fuzzy rules
      provide a natural mean of incorporating the bias components for rapid
      reinforcement learning. Experimental results and comparative studies with the
      fuzzy Q-learning (FQL) and continuous-action Q-learning in the wall-following
      task of mobile robots demonstrate that the proposed DFQL method is superior.

PMID- 15484919
TI  - On a multimode test sequencing problem.
AB  - Test sequencing is a binary identification problem wherein one needs to develop a
      minimal expected cost test procedure to determine which one of a finite number of
      possible failure states, if any, is present. In this paper, we consider a
      multimode test sequencing (MMTS) problem, in which tests are distributed among
      multiple modes and additional transition costs will be incurred if a test
      sequence involves mode changes. The multimode test sequencing problem can be
      solved optimally via dynamic programming or AND/OR graph search methods. However,
      for large systems, the associated computation with dynamic programming or AND/OR
      graph search methods is substantial due to the rapidly increasing number of OR
      nodes (denoting ambiguity states and current modes) and AND nodes (denoting next
      modes and tests) in the search graph. In order to overcome the computational
      explosion, we propose to apply three heuristic algorithms based on information
      gain: information gain heuristic (IG), mode capability evaluation (MC), and mode
      capability evaluation with limited exploration of depth and degree of mode
      Isolation (MCLEI). We also propose to apply rollout strategies, which are
      guaranteed to improve the performance of heuristics, as long as the heuristics
      are sequentially improving. We show computational results, which suggest that the
      information-heuristic based rollout policies are significantly better than
      traditional information gain heuristic. We also show that among the three
      information heuristics proposed, MCLEI achieves the best tradeoff between
      optimality and computational complexity.

PMID- 15484920
TI  - Edge detection revisited.
AB  - The present manuscript aims at solving four problems of edge detection: the
      simultaneous detection of all step edges from a fine to a coarse scale; the
      detection of thin bars with a width of very few pixels; the detection of
      trihedral junctions; the development of an algorithm with image-independent
      parameters. The proposed solution of these problems combines an extensive spatial
      filtering with classical methods of computer vision and newly developed
      algorithms. Step edges are computed by extracting local maxima from the energy
      summed over a large bank of directional odd filters with a different scale. Thin
      roof edges are computed by considering maxima of the energy summed over narrow
      odd and even filters along the direction providing maximal response. Junctions
      are precisely detected and recovered using the output of directional filters. The
      proposed algorithm has a threshold for the minimum contrast of detected edges:
      for the large number of tested images this threshold was fixed equal to three
      times the standard deviation of the noise present in usual acquisition system
      (estimated to be between 1 and 1.3 gray levels out of 256), therefore, the
      proposed scheme is in fact parameter free. This scheme for edge detection
      performs better than the classical Canny edge detector in two quantitative
      comparisons: the recovery of the original image from the edge map and the
      structure from motion task. As the Canny detector in previous comparisons was
      shown to be the best or among the best detectors, the proposed scheme represents
      a significant improvement over previous approaches.

PMID- 15484921
TI  - Annealing by two sets of interactive dynamics.
AB  - This work derives the mean field approximation to the mean configuration of a
      stochastic Hopfield neural network under the Boltzmann assumption. The new
      approximation is realized by two sets of interactive mean field equations,
      respectively estimating mean activations subject to mean correlations and mean
      correlations subject to mean activations. The two sets of interactive dynamics
      are derived based on two dual mathematical frameworks. Each aims to optimize the
      objective quantified by a combiation of the Kullback-Leibler (KL) divergence and
      the correlation strength between any two distinct fluctuated variables subject to
      fixed mean correlations or activations. The new method is applied to the graph
      bisection problem. By numerical simulations, we show that the new method
      effectively improves in both performance and relaxation efficiency against the
      naive mean field equation

PMID- 15484922
TI  - Enhanced sound localization.
AB  - A new approach to sound localization, known as enhanced sound localization, is
      introduced, offering two major benefits over state-of-the-art algorithms. First,
      higher localization accuracy can be achieved compared to existing methods.
      Second, an estimate of the source orientation is obtained jointly, as a
      consequence of the proposed sound localization technique. The orientation
      estimates and improved localizations are a result of explicitly modeling the
      various factors that affect a microphone's level of access to different spatial
      positions and orientations in an acoustic environment. Three primary factors are
      accounted for, namely the source directivity, microphone directivity, and source
      microphone distances. Using this model of the acoustic environment, several
      different enhanced sound localization algorithms are derived. Experiments are
      carried out in a real environment whose reverberation time is 0.1 seconds, with
      the average microphone SNR ranging between 10-20 dB. Using a 24-element
      microphone array, a weighted version of the SRP-PHAT algorithm is found to give
      an average localization error of 13.7 cm with 3.7% anomalies, compared to 14.7 cm
      and 7.8% anomalies with the standard SRP-PHAT technique.

PMID- 15484923
TI  - Constrained motion control of flexible robot manipulators based on recurrent
      neural networks.
AB  - In this paper, a neural network approach is presented for the motion control of
      constrained flexible manipulators, where both the contact force everted by the
      flexible manipulator and the position of the end-effector contacting with a
      surface are controlled. The dynamic equations for vibration of flexible link and
      constrained force are derived. The developed control, scheme can adaptively
      estimate the underlying dynamics of the manipulator using recurrent neural
      networks (RNNs). Based on the error dynamics of a feedback controller, a learning
      rule for updating the connection weights of the adaptive RNN model is obtained.
      Local stability properties of the control system are discussed. Simulation
      results are elaborated on for both position and force trajectory tracking tasks
      in the presence of varying parameters and unknown dynamics, which show that the
      designed controller performs remarkably well.

PMID- 15484924
TI  - A real-time architecture for time-aware agents.
AB  - This paper describes the specification and implementation of a new three-layer
      time-aware agent architecture. This architecture is designed for applications and
      environments where societies of humans and agents play equally active roles, but
      interact and operate in completely different time frames. The architecture
      consists of three layers: the April real-time run-time (ART) layer, the time
      aware layer (TAL), and the application agents layer (AAL). The ART layer forms
      the underlying real-time agent platform. An original online, real-time, dynamic
      priority-based scheduling algorithm is described for scheduling the computation
      time of agent processes, and it is shown that the algorithm's O(n) complexity and
      scalable performance are sufficient for application in real-time domains. The TAL
      layer forms an abstraction layer through which human and agent interactions are
      temporally unified, that is, handled in a common way irrespective of their
      temporal representation and scale. A novel O(n2) interaction scheduling algorithm
      is described for predicting and guaranteeing interactions' initiation and
      completion times. The time-aware predicting component of a workflow management
      system is also presented as an instance of the AAL layer. The described time
      aware architecture addresses two key challenges in enabling agents to be
      effectively configured and applied in environments where humans and agents play
      equally active roles. It provides flexibility and adaptability in its real-time
      mechanisms while placing them under direct agent control, and it temporally
      unifies human and agent interactions.

PMID- 15484925
TI  - Comments on "A computational evolutionary approach to evolving game strategies
      and cooperation".

PMID- 15484926
TI  - Fuzzy disturbance observer approach to robust tracking control of nonlinear
      sampled systems with the guaranteed suboptimal H infinity performance.

PMID- 15484927
TI  - Perception control with improved expectation learning through multilayered neural
      networks.

PMID- 15484928
TI  - Facial expression recognition using constructive feedforward neural networks.

PMID- 15484929
TI  - Adaptive robust fuzzy control of nonlinear systems.

PMID- 15484930
TI  - Flexible negotiation agent with relaxed decision rules.

PMID- 15484931
TI  - Design of optimal controller for interval plant from signal energy point of view
      via evolutionary approaches.

PMID- 15484932
TI  - Learning activity patterns using fuzzy self-organizing neural network.

PMID- 15484933
TI  - New alleles in calpastatin gene are associated with meat quality traits in pigs.
AB  - Suggestive QTL affecting raw firmness scores and average Instron force,
      tenderness, juiciness, and chewiness on cooked meat were mapped to pig chromosome
      2 using a three-generation intercross between Berkshire and Yorkshire pigs. Based
      on its function and location, the calpastatin (CAST) gene was considered to be a
      good candidate for the observed effects. Several missense and silent mutations
      were identified in CAST and haplotypes covering most of the coding region were
      constructed and used for association analyses with meat quality traits. Results
      demonstrated that one CAST haplotype was significantly associated with lower
      Instron force and cooking loss and higher juiciness and, therefore, this
      haplotype is associated with higher eating quality. Some of the sequence
      variation identified may be associated with differences in phosphorylation of
      CAST by adenosine cyclic 3', 5'-monophosphate-dependent protein kinase and may in
      turn explain the meat quality phenotypic differences. The beneficial haplotype
      was present in all the commercial breeds tested and may provide significant
      improvements for the pig industry and consumers because it can be used in marker
      assisted selection to produce naturally tender and juicy pork without additional
      processing steps.

PMID- 15484934
TI  - Genotype x environment interactions and genetic parameters for fecal egg count
      and production traits of Merino sheep.
AB  - Breeding for host resistance to parasites has become an imperative in many sheep
      industries. Because of the widespread use of AI in sheep breeding schemes, it is
      important to understand how the performance of offspring from rams varies in
      different flock environments, both for resistance to parasites and key production
      traits. This study used both variance component and reaction norm models to
      investigate the level of genotype x environment interaction for fecal egg count
      (FEC) and important Merino production traits in a range of flock environments in
      Australia. These flocks were linked by the use of common rams in a sire
      referencing scheme. Both linear and quadratic polynomial reaction norm models
      were used. The heritability of these traits and the genetic correlation between
      them and FEC also was investigated using the reaction norm model. A contemporary
      group (CG) was defined by a flock, year, age class, sex, and paddock combination.
      Each CG environment was characterized by the mean value of any given trait for
      that CG. The recorded data used in the study were analyzed in a standardized
      form. Standardization for each trait was achieved within a CG by subtracting the
      CG mean from each observation and dividing by the CG SD. The genotype x
      environment effect accounted for <0.05 of the phenotypic variance for all traits.
      In most traits the heritability varied little across environments. The exceptions
      were FEC, BW, and both greasy and clean fleece weights, which had a higher
      heritability at the lower end of the environmental range. Fecal egg count also
      had a higher heritability in high-FEC environments. Genetic correlations between
      FEC and several key production traits were similar in the flock environments
      studied. Quadratic polynomial models and models with a variable residual fitted
      the data better than linear models. The genotype x environment effect for FEC and
      the genetic correlations between FEC and production traits were effectively zero;
      thus, sheep breeding programs for increased parasite resistance can be run
      effectively by ignoring these factors. Some account should be taken of the high
      heritabilities of FEC and fleece and BW in different flock environments.

PMID- 15484935
TI  - Genetic parameters for indicators of host resistance to parasites from weaning to
      hogget age in Merino sheep.
AB  - Fecal egg count (FEC) has been widely used as an indicator of host resistance to
      gastrointestinal parasites in sheep and has been shown to be a heritable trait.
      Two other possible indicators of parasites, dag score (DS; accumulated fecal
      material) and fecal consistency score (FCS), were investigated in this study,
      along with BW. All four traits were studied to see how heritability and genetic
      correlations varied with age from weaning (4 mo) to hogget age (approximately 400
      d). More than 1,100 lambs, the offspring of 37 rams, were recorded eight times
      between weaning (3 to 5 mo of age) and hogget age (13 to 18 mo of age) on two
      farms. Sire models were fitted to the data from each trait at each recording and
      in a repeatability model involving the whole data set. Overall, the
      heritabilities were 0.28+/-0.072 (FEC), 0.11+/-0.036 (DS), 0.12+/-0.036 (FCS),
      and 0.23+/-0.070 (BW). By fitting random regression models to the time-series
      data, it was possible to see how these heritability values varied as the lambs
      aged, from weaning to hogget age. The heritability of FEC rose from 0.2 at
      weaning to 0.65 at 400 d. Dag score had a higher heritability (0.25) in the
      middle of the age range and a low value at weaning (<0.1) and hogget age (0.16).
      The heritability of FCS was low, with a value of 0.2 at weaning reducing to 0.05
      as the animals aged. Body weight had zero heritability at weaning, which rose to
      greater than 0.6 at hogget age. Most traits had low genetic correlations between
      them, the only exception being that between FCS and DS (0.63). Most genetic
      correlations varied little over the age range with the exception of FEC and BW,
      which fell from 0 at weaning to -0.63 at hogget age. Whereas FCS and DS may be
      good indicators of scouring, they are very different from FEC as an indicator of
      host resistance to gastrointestinal parasites.

PMID- 15484936
TI  - Selection for growth in brown trout increases feed intake capacity without
      affecting maintenance and growth requirements.
AB  - The correlated responses in feed intake and G:F ratio with selection for
      increased growth rate were evaluated by comparing selected (S) and control (C)
      brown trout (Salmo trutta) reared under conditions known to affect feed
      efficiency: feed restriction and periods of compensatory growth. Nitrogen and
      energy requirements for maintenance and growth were also measured. Trout were
      allotted at comparable BW (3.7+/-0.06 and 3.8+/-0.04 g, for C and S respectively)
      to triplicate groups per treatment. The experiment lasted a total of 198 d,
      during which animals were successively submitted to a 116-d feeding phase and fed
      10, 30, 50, 70, 100, and 140% of their usual daily ration (UDR), a 35-d phase of
      food deprivation, and a 47-d refeeding phase. The G:F of C and S were comparable
      in all experimental conditions tested. During the feeding phase, S grew better
      than C only when fed 100 and 140% UDR (P < 0.001). This was explained by a higher
      feed intake capacity. The requirements for growth and maintenance were similar
      among the lines, which is in agreement with their comparable loss of weight (mean
      energy loss of -53 and -55 kJ/(kg x d) for C and S, respectively; P > 0.38)
      observed during the feed deprivation phase and the lack of differences in carcass
      composition (fat, P > 0.35; protein, P > 0.54). During the refeeding phase,
      growth performance and G:F were high in all groups. The daily growth coefficient
      was higher in S than in C (P < 0.001) because of a higher feed intake (P <
      0.001). An increase in absolute individual variability in final BW and length was
      associated with the level of food restriction in both lines; however, it always
      remained lower in S than in C. In conclusion, fish selected for growth under ad
      libitum conditions will only exhibit growth superiority when fed diets close to
      ad libitum, and there was no evidence that selection was associated with an
      improvement in efficiency of maintenance nor in retention of body tissues.

PMID- 15484937
TI  - Performance of mouse lines divergently selected for heat loss when exposed to
      different environmental temperatures. I. Reproductive performance, pup survival,
      and metabolic hormones.
AB  - Mouse populations differing in metabolic rate have been developed through
      selection for high (MH) and low (ML) heat loss, along with the unselected
      controls (MC). Objectives of the study were to compare the MH, ML, and MC lines
      for reproductive performance, pup survival, and metabolic hormones when reared at
      12, 22, and 31 degrees C, and to search for line x environment interactions.
      Conception and litter size were recorded on the parent generation mice introduced
      to the environments at 11 wk of age and bred after a 3-wk acclimatization period.
      Survival of pups (preweaning to 3 wk; postweaning from 3 to 9 wk of age) was
      measured with continuous exposure in the designated environment from birth to the
      time of measurement. Corticosterone, triiodothyronine (T3), and thyroxine (T4)
      serum concentrations were measured on the parent generation after producing
      litters and on the pup generation at 9 wk. No line x environment interaction was
      detected for conception rate, preweaning mortality, postweaning survival, pup
      weaning weight, or body temperature. There were no differences in conception rate
      among lines and environments. Environments affected survival of pups, but there
      were no line differences. Rectal body temperatures were greater for MH than ML
      mice, and MC mice were intermediate; body temperature of mice did not differ
      among the environments. Lines differed significantly in litter size only in the
      22 degrees C environment. No significant line differences were found for serum
      corticosterone or serum T3 or T4. Line x environment interaction was detected
      only for litter size and for serum corticosterone concentration in dams. Contrary
      to the other two lines, ML dam performance relative to MH and MC was not affected
      negatively by either of the thermal environments. Results from this study do not
      raise concern that selection to decrease maintenance requirements will produce
      livestock with any greater liability to cope and perform under an array of
      environmental temperatures.

PMID- 15484938
TI  - Performance of mouse lines divergently selected for heat loss when exposed to
      different environmental temperatures. II. Feed intake, growth, fatness, and body
      organs.
AB  - Mouse populations differing in metabolic rate have been developed through
      selection for high (MH) and low (ML) heat loss, along with the unselected
      controls (MC). Objectives of the study were to compare the MH, ML, and MC lines
      for feed intake, growth, body fatness, and organ weights when reared at 12, 22,
      and 31 degrees C, and investigate potential line x environment interactions. Feed
      intake was recorded weekly from 3 to 9 wk of age, and BW at 3, 6, and 9 wk of
      age. Body fat percent and organ weights were measured at 9 wk of age. No line x
      environment interactions were detected for any of the traits measured. The MH
      mice consumed more feed than ML mice from 5 to 9 wk of age. Between 8 and 9 wk of
      age, MH mice consumed 13% more feed than the ML mice, but they were relatively
      leaner (14.45 vs. 16.32% body fat); MC mice were intermediate for both traits.
      Mice in the cold environment consumed the greatest amount of feed, and those in
      the hot environment consumed the least. Males consumed more feed than females,
      and the difference was greater in the cold than in the hot environment. No
      differences in BW were found between the lines. Mice in the 22 degrees C
      environment were heavier than their age-matched counterparts in the other two
      environments, and males were heavier than females at all ages. Relative to BW,
      the three lines had similar tail length, body length, and liver weight. Mice in
      the cold environment had heavier spleens and livers than those in the hot
      environment but relatively shorter bodies and tails; the normal environment was
      intermediate for these traits. Results from this study indicate that selection to
      decrease maintenance requirements did not produce mice with any less ability to
      grow and perform under an array of environmental temperatures.

PMID- 15484939
TI  - Competing risks analysis of lamb mortality in a terminal sire composite
      population.
AB  - Mortality records from birth to weaning of 8,301 lambs from a composite
      population at the U.S. Meat Animal Research Center were analyzed using a
      competing risks model. The advantage of the competing risks model over
      traditional survival analyses is that different hazards of mortality can be
      assigned to different causes, such as disease, dystocia, and starvation. In this
      study, specific causes of mortality were grouped into dam-related (DAMR; e.g.,
      dystocia and starvation), pneumonia (PNEU), disease (DIS; excluding pneumonia),
      and other (OTHER) categories. The hazard of mortality was analyzed using a
      competing risk approach, where each mortality category was assumed to be
      independent. Continuous- and discrete-time survival analyses were implemented
      using sire, animal, and maternal effects mixed models. The continuous-time
      survival analysis used the Weibull model to describe the hazard of mortality for
      each category of mortality. Under the discrete-time survival analysis, a
      complementary log-log link function was used to analyze animal-time data sets
      using weekly intervals for each category of mortality. Explanatory variables were
      sex, type of birth, contemporary group, and age of dam. The significant
      influences of type of birth and age of dam effects were consistent across
      category of mortality, and the sex effect was significant for all categories
      except the OTHER category. Estimates of variance components indicated strong
      maternal effects for all categories except for PNEU. Estimates of additive
      genetic heritabilities from the discrete maternal effects models were 0.08+/
      0.04, 0.09+/-0.18, 0.16+/-0.12, 0.19+/-0.09, and 0.14+/-0.10 for OVERALL (all
      causes combined), DIS, DAMR, PNEU, and OTHER categories, respectively. Ignoring
      the cause of the defining event in mortality and longevity studies may hide
      important genetic differences. Therefore, the effectiveness of breeding programs
      relying on models that ignore multiple causes of an event in time-to-event data,
      such as mortality and longevity, could be affected.

PMID- 15484940
TI  - Genetic diversity in and conservation strategy considerations for Navajo Churro
      sheep.
AB  - The objectives of this study were to 1) evaluate the genetic diversity of Navajo
      Churro sheep using pedigree information; 2) examine the distribution of the
      Navajo-Churro population; and 3) evaluate the effect of breeder dynamics on
      genetic conservation of the breed. Pedigree data and breeder information (city
      and state) were obtained from the Navajo-Churro Sheep Breed Association.
      Inbreeding coefficients were calculated for each individual animal using pedigree
      information. A geographic information system program was used to divide the
      United States into four regions and overlay breeder locations, flock size, and
      flock inbreeding level. The small correlation between level of inbreeding and
      flock size (r = -0.07, P = 0.07) indicated that inbreeding levels are not
      different across flock sizes. The mean flock inbreeding levels ranged from 0 to
      11% across regions. The level of inbreeding did not differ among regions (P =
      0.15), except for Region 4 (Kansas and Missouri; P = 0.001). The number of
      breeders registering sheep averaged 34 per year. Most of the breeders were
      transient, with only eight breeders maintaining ownership for more than 7 yr.
      Average inbreeding level for 2000 was found to be 1.2%, with a linear increase in
      inbreeding of 0.1%/yr over the period studied, suggesting a minimal loss of
      genetic diversity for the Navajo-Churro. However, given the relatively small
      effective population size (92) and the transient nature of the breeders,
      development of an ex situ cryo-preserved germplasm bank may be the best long-term
      strategy for maintaining this breed's genetic diversity.

PMID- 15484941
TI  - Population structure of a colony of dog guides.
AB  - The objective of this study was to describe changes in genetic diversity in a
      colony of dog guides since its founding. Two breeds, German Shepherds (GS) and
      Labrador Retrievers (LR), were evaluated. Data were pedigrees of 4,699 GS and
      3,573 LR dogs bred for use as guides by The Seeing Eye, Inc., Morristown, NJ.
      Rapid increases in average pairwise numerator relationships occurred in both
      breeds, although the average was approximately one-third higher in the GS
      population than in the LR population. A similar trend was observed for average
      inbreeding. The rate of increase in inbreeding has slowed in recent generations.
      In the current generation, relationship and inbreeding for all animals averaged
      25.3 and 26.2% in GS, and 15.5 and 22.0% in LR, respectively. Effective founder
      numbers initially decreased in GS until Generation 3, and then increased
      steadily. Effective founder number in LR constantly increased. There was a
      constant increase in effective founder number in LR. A similar pattern was noted
      for effective ancestor number as well. Founder genome equivalents were initially
      higher in GS but decreased over time in both breeds. Generation intervals
      averaged 23.7 mo in GS and 23.2 mo in LR. Sires had average service lives of 2.7
      and 2.2 generations in GS and LR, respectively. Dams had average service lives of
      2.1 generations in both breeds. Litter sizes averaged 5.1 and 7.4 pups per litter
      for GS and LR, respectively. Effective founder and ancestor numbers have slowly
      increased over time, and heterozygosity as measured by the number of founder
      genome equivalents in the population has increased. Limitations on the number of
      matings permitted for sires and service life of dams has led to a plateau for
      inbreeding and relationships. The importation of germplasm from other working dog
      colonies is desirable.

PMID- 15484942
TI  - Association of myostatin on early calf mortality, growth, and carcass composition
      traits in crossbred cattle.
AB  - The objective of this study was to investigate a potential association of an
      inactive myostatin allele with early calf mortality, and evaluate its effect on
      growth and carcass traits in a crossbred population. Animals were obtained by
      mating F1 cows to F1 (Belgian Blue x British Breed) or Charolais sires. Cows were
      obtained from mating Hereford, Angus, and MARC III (1/4 Hereford, 1/4 Angus, 1/4
      Pinzgauer, and 1/4 Red Poll) dams to Hereford, Angus, Tuli, Boran, Brahman, or
      Belgian Blue sires. Belgian Blue was the source of the inactive myostatin allele.
      Myostatin genotypes were determined for all animals including those that died
      before weaning. Early calf mortality was examined in the F2 subpopulation (n =
      154), derived from the F1 sires mated to F1 cows from Belgian Blue sires, to
      evaluate animals with zero, one, or two copies of inactive myostatin allele. An
      overall 1:2:1 ratio (homozygous active myostatin allele:heterozygous:homozygous
      inactive myostatin allele) was observed in the population; however, a comparison
      between calves dying before weaning and those alive at slaughter showed an
      unequal distribution across genotypes (P < 0.01). Calves with two copies of the
      inactive allele were more likely (P < 0.01) to die before weaning. Postweaning
      growth traits were evaluated in the surviving animals (n = 1,370), including
      birth, weaning, and live weight at slaughter, and postweaning ADG. Carcass
      composition traits analyzed were hot carcass weight, fat thickness, LM area,
      marbling score, USDA yield grade, estimated kidney, pelvic, and heart fat, retail
      product yield and weight, fat yield and weight, bone yield and weight, and
      percentage of carcasses classified as Choice. Charolais lack the inactive
      myostatin allele segregating in Belgian Blue; thus, in the population sired by
      Charolais (n = 645), only animals with zero or one copy of the inactive myostatin
      allele were evaluated. Animals carrying one copy were heavier at birth and at
      weaning, and their carcasses were leaner and more muscled. In the population
      sired by Belgian Blue x British Breed (n = 725), animals with two copies of
      inactive myostatin allele were heavier at birth, leaner, and had a higher
      proportion of muscle mass than animals with zero or one copies. Heterozygous
      animals were heaviest at weaning and had the highest live weight, whereas animals
      with zero copies had the highest fat content. The use of the inactive myostatin
      allele is an option to increase retail product yield, but considerations of
      conditions at calving are important to prevent mortality.

PMID- 15484943
TI  - Effects of short-term early gestational exposure to endophyte-infected tall
      fescue diets on plasma 3,4-dihydroxyphenyl acetic acid and fetal development in
      mares.
AB  - Consumption of wild-type (toxic) endophyte-infected tall fescue (E+) by horses
      during late gestation is known to adversely affect pregnancy outcome; however,
      little is known of the potential disruptive consequences of E+ consumption by
      mares during the critical phases of placentation and fetal development in early
      pregnancy. The objective of this study was to evaluate the detrimental effects of
      feeding E+ to mares during early gestation. Mares (n = 12) paired by stage of
      gestation (d 65 to 100) were assigned to diets (six per diet) consisting of
      endophyte-free (E-) or E+ tall fescue seed (50% E- or E+ tall fescue seed, 45%
      sweet feed, and 10% molasses fed at 1.0% of BW/d). Mares also had ad libitum
      access to E+ or E- annual ryegrass hay, and were fed diets for 10 d. Following
      removal from the tall fescue diet on d 11, mares were placed on common
      bermudagrass pasture and monitored until d 21. Morning and evening rectal
      temperatures were recorded and daily blood samples were collected for
      progesterone and prolactin (PRL) analyses, whereas samples for 3,4
      dihydroxyphenyl acetic acid (a catecholamine metabolite) analysis were collected
      on alternate days. For clinical chemistry analysis, blood samples were collected
      on d 0, 5, 10 and 21. Daily urine samples were collected for ergot alkaloid
      analysis, and ultrasonography was performed for presence of echogenic material in
      fetal fluids. Rectal temperatures (E+ 37.76+/-0.03; E- 37.84+/-0.03 degrees C)
      and serum PRL concentrations (E+ 14.06< or =0.76; E- 12.11+/-0.76 ng/mL) did not
      differ (P = 0.96) between treatments. Measuring the change in basal serum
      concentration from d 0 over time, progesterone concentrations did not differ (
      0.64 +/-1.49 and -0.55+/-1.47 ng/mL for E+ and E- mares, respectively). There was
      no negative pregnancy outcome, and ultrasonography indicated no increase in
      echogenic material in fetal fluids. Plasma 3,4-dihydroxyphenyl acetic acid
      concentrations decreased (P < 0.05) in E+ compared with E- mares (2.1+/-0.14 and
      4.4+/0.43 ng/mL, respectively). Urinary ergot alkaloid concentration was greater
      (P < 0.01) in mares consuming E+ compared with E- (532.12+/- 52.51 and 13.36+/
      2.67 ng/mg of creatinine, respectively). Although no fetal loss was observed
      during the current study, elevated concentrations of urinary ergot alkaloid were
      consistent with depressed endogenous catecholamine activity, suggestive of an
      endocrine disruptive effect of hypothalamic origin.

PMID- 15484944
TI  - Chronic administration of recombinant ovine leptin in growing beef heifers:
      effects on secretion of LH, metabolic hormones, and timing of puberty.
AB  - Serum concentrations of leptin increase linearly from approximately 16 wk before
      until the week of pubertal ovulation in beef heifers. To test the hypothesis that
      exogenous leptin can hasten the onset of puberty in heifers, we examined the
      effects of chronic administration of recombinant ovine leptin (oleptin) on timing
      of puberty, pulsatile and GnRH-mediated release of LH, and plasma concentrations
      of GH, IGF-I, and insulin. Fourteen fall-born, prepubertal heifers (Brahman x
      Hereford, 12 to 13 mo; 304.7+/-4.12 kg) were used. Heifers were stratified by age
      and BW and assigned randomly to one of two groups (seven animals per group): 1)
      Control; heifers received s.c. injections of saline twice daily (0700 and 1900)
      for 40 d; and 2) Leptin; heifers received s.c. injections of oleptin (19.2
      microg/kg) twice daily at 0700 and 1900 for 40 d. Blood samples were collected at
      10-min intervals for 5 h on. d 0, 5, 10, 20, 30, and 40, and twice daily, just
      before each treatment injection, throughout the study. On d 41, heifers received
      i.v. injections of GnRH at 0 (0.0011 microg/kg) and 90 min (0.22 microg/kg), with
      additional sampling for 5.5 h to examine releasable pools of LH. Diets promoted a
      gain of 0.32+/-0.09 kg/d, which did not differ between groups. Plasma
      concentrations of leptin increased markedly in leptin-treated heifers and were
      greater (P < 0.001) than controls throughout (27.8+/-0.8 vs. 4.9+/-0.12 ng/mL).
      None of the heifers reached puberty during the experiment, but did so within 45 d
      of its termination. Mean concentrations of plasma LH, GH, IGF-I, and insulin were
      not affected by treatment, nor was there an overall effect on the frequency of LH
      pulses. However, a treatment x day interaction (P = 0.02) revealed that the
      frequency of LH pulses (pulses/ 5 h) was greater (P = 0.03) in controls (3.6+/
      0.36) than in leptin-treated heifers (1.7+/- 0.28) on d 10. Characteristics of
      GnRH-induced release of LH were not affected by treatment. In summary,
      chronically administered leptin failed to induce puberty or alter endocrine
      characteristics in beef heifers nearing the time of expected puberty.

PMID- 15484945
TI  - Effects of rancidity and free fatty acids in choice white grease on growth
      performance and nutrient digestibility in weanling pigs.
AB  - Two experiments were conducted to determine the effects of rancidity and FFA in
      choice white grease (CWG) on growth performance and nutrient digestibility in
      nursery pigs. In Exp. 1,150 crossbred pigs (average initial BW of 6.8 kg and
      average initial age of 21 d) were used. Treatments (as-fed basis) were a corn
      soybean meal-based control with no added fat, 6% CWG, and 6% CWG heated at 80
      degrees C, with oxygen gas bubbled through it at 849 mL/min for 5, 7, 9, or 11 d.
      Peroxide value for the CWG increased as oxidative exposure was increased from 0
      to 7 d (i.e., peroxide values of 1, 40, and 105 mEq/kg for d 0, 5, and 7,
      respectively), but decreased to 1 mEq/kg as the hydroperoxides decomposed after 9
      and 11 d of oxidation. Pigs fed the control diet (no added fat) had the same (P =
      0.91) overall ADG (d 0 to 35) but lower G:F (P < 0.04) than pigs fed diets with
      added fat. As for the effects of fat quality, ADG (linear effect, P < 0.01) and
      ADFI (linear effect, P < 0.001) decreased as the fat was made more rancid.
      However, there were no changes in digestibility of fatty acids as the rancidity
      of the fat was increased (P = 0.16), suggesting that the negative effects of
      rancidity were from decreased food intake and not decreased nutrient utilization.
      In Exp. 2, 125 crossbred pigs (average initial BW of 6.2 kg and average initial
      age of 21 d) were used to determine the effects of FFA in CWG on the growth
      performance and nutrient digestibility in nursery pigs. Treatments (as-fed basis)
      were a corn-soybean meal-based control with no added fat, 6% CWG, and 6% CWG that
      had been treated with 872, 1,752 or 2,248 lipase units/g of fat. The FFA
      concentrations in the CWG were increased from 2% with no lipase added to 18, 35,
      and 53% as lipase additions were increased. Pigs fed the control diet (no added
      fat) had the same (P = 0.30) overall ADG (d 0 to 33) but lower G:F (P < 0.01)
      than pigs fed diets with added fat. There were no effects of FFA concentration on
      ADG (P = 0.18), and ADFI increased (linear effect, P < 0.04) as FFA concentration
      in the CWG increased. Fatty acid digestibility was not affected (P = 0.17) by FFA
      in the diet. In conclusion, our data suggest that as fat is oxidized (especially
      to peroxide values greater than 40 mEq/kg), ADG and ADFI in nursery pigs will
      decrease; however, FFA concentrations of at least 53% do not adversely affect
      utilization of CWG in nursery pigs.

PMID- 15484946
TI  - Phosphorus requirements of growing-finishing pigs reared in a commercial
      environment.
AB  - The objective of this study was to identify available phosphorus (aP)
      requirements of pigs reared in commercial facilities. In a preliminary study, 600
      gilts (PIC) were allotted randomly to low (0.30%) or high (0.37%) dietary aP from
      43 to 48 kg BW, and later to 0.19 or 0.27% aP from 111 to 121 kg BW. No
      differences were observed (P = 0.42 to 0.88) in ADG, but G:F from 43 to 48 kg
      tended to improve (P = 0.07) for pigs fed low aP. Results suggested that the aP
      requirement was at or below 0.30 and 0.19%. These concentrations were used to
      titrate aP requirements in Exp. 1 and 2. In Exp. 1, 1,260 gilts (initially 33.8
      kg) were allotted randomly to one of five dietary treatments containing 0.18,
      0.22, 0.25, 0.29, or 0.32% aP, corresponding to 0.5, 0.6, 0.7, 0.8, or 0.9 g of
      aP/Mcal of ME. There were 28 pigs per pen and nine pens per treatment. From d 0
      to 14, increasing aP increased ADG (linear, P = 0.03) and G:F (quadratic, P =
      0.07), with the greatest response observed as aP increased from 0.18 to 0.22%
      (G:F breakpoint = 0.22%). However, from d 0 to 26, no differences (P = 0.12 to
      0.81) were observed for any growth traits. Pooled bending moment of the femur,
      sixth rib, and third and fourth metatarsals increased (linear, P = 0.007) with
      increasing aP. In Exp. 2, 1,239 gilts (initially 88.5 kg BW) were randomly
      allotted to one of five dietary treatments containing 0.05, 0.10, 0.14, 0.19, or
      0.23% aP, equivalent to 0.14, 0.28, 0.39, 0.53, or 0.64 g of aP/Mcal of ME. The
      diet with 0.05% aP contained no added inorganic P. From d 0 to 14, increasing aP
      increased (linear, P = 0.008 to 0.02) ADG and G:F; however, from d 0 to 28,
      increasing aP had no effect (P = 0.17 to 0.74) on growth performance. Increasing
      aP increased (linear, P < 0.001 to 0.04) metacarpal bone ash percent and bending
      moment. Results suggest that 33- to 55-kg pigs require approximately 0.22% aP,
      which corresponds to 0.60 g of aP/Mcal of ME or 3.30 g of aP/d to maximize ADG
      and G:F compared with NRC (1998) estimates of 0.23%, 0.70 g of aP/Mcal of ME, and
      4.27 g of aP/d for 20- to 50-kg pigs. Finishing pigs (88 to 109 kg) require at
      least 0.19% aP, corresponding to 0.53 g of aP/Mcal of ME or 4.07 g aP/d compared
      with NRC (1998) estimates of 0.15%, 0.46 g of aP/Mcal of ME and 4.61 g of aP/d
      for 80- to 120-kg pigs. However, the percentage of bone ash and bending moment
      continued to increase with increasing aP. These data also suggest that complete
      removal of supplemental P in diets for finishing pigs (>88 kg) will decrease ADG
      and G:F.

PMID- 15484947
TI  - Dietary protein concentration affects plasma arteriovenous difference of amino
      acids across the porcine mammary gland.
AB  - The objective of this study was to determine whether the porcine mammary gland
      responds to increasing dietary CP concentration through changes in AA
      arteriovenous difference (a-v). Sixteen Landrace x Yorkshire lactating sows were
      provided ad libitum access to one of four isocaloric diets varying in CP
      concentration (7.8, 13.0, 18.2, and 23.5 %; as-fed basis). Litters were adjusted
      to 11 pigs within 48 h of birth. Sows were fitted with catheters in the carotid
      artery and main mammary vein on d 4. On d 10, 14, 18, and 22 of lactation,
      arterial and venous blood samples were obtained every 30 min over 6 h. Milk yield
      was estimated on d 11 and 21 using the D2O dilution technique. Final litter sizes
      on d 21 were 10.3, 11, 9.5, and 11 piglets for sows fed the 7.8, 13.0, 18.2, and
      23.5% CP diets, respectively. Piglet ADG tended (P = 0.088) to increase with
      increasing dietary CP concentration and were 186, 221, 220, and 202 g for sows
      fed the 7.8, 13.0, 18.2, and 23.5% CP diet, respectively. Daily total milk yield
      on d 21 (kg milk/d) tended (P = 0.099) to increase, and average milk yield per
      nursed piglet (kg of milk-pig(-1)d(-1)) increased (P < 0.05) with increasing CP
      concentration and were, on a per-piglet basis, 0.95, 1.19, 1.14 and 1.13 kg of
      milk/d for the 7.8, 13.0, 18.2, and 23.5% CP diets, respectively. As dietary CP
      increased from 7.8 to 23.5%, isoleucine and leucine a-v increased linearly only
      (linear, P < 0.01); all other AA a-v increased, reached a maximum in sows fed
      18.2% CP, and decreased thereafter in sows fed 23.5% CP (quadratic, from P = 0.10
      to P < 0.05). Amino acid uptake by the entire udder and by each gland increased
      (linear, P < 0.05) with increasing dietary CP. Arteriovenous differences response
      to increasing day of lactation varied among AA, from no change for histidine,
      isoleucine, lysine, methionine, tryptophan, and valine, to a linear trend
      increase for arginine (P = 0.055), leucine (P = 0.064), phenylalanine (P =
      0.101), and threonine (P = 0.057). In summary, for the majority of AA, a-v
      increased with increasing dietary CP concentration from 7.8 to 18.2%, but
      decreased when CP concentration exceeded 18.2%. In contrast, mammary AA uptake,
      piglet ADG and milk yield per pig increased linearly with increasing dietary CP,
      suggesting a coordinated regulation between AA delivery and transport to meet the
      demand for milk yield.

PMID- 15484948
TI  - Effects of additional starch or fat in late-gestating high nonstarch
      polysaccharide diets on litter performance and glucose tolerance in sows.
AB  - The effects of feeding additional starch or fat from d 85 of gestation until
      parturition on litter performance and on glucose tolerance in sows that were fed
      a diet with a high level of fermentable nonstarch polysaccharides (NSP) were
      studied. The day after breeding, 141 multiparous sows were assigned to the
      experiment. At d 85 of gestation, sows were assigned to the treatments. Sows were
      fed 3.4 kg/d (as-fed basis) of a high-NSP diet or the same quantity of the high
      NSP diet and an additional 360 g of starch (from wheat starch) daily, or the same
      quantity of the high-NSP diet and an additional 164 g of fat (from soybean oil)
      daily. During lactation, all sows were given free access to the same lactation
      diet. Approximately 1 wk before the expected time of parturition, an oral glucose
      tolerance test was performed in 38 randomly chosen sows by feeding pelleted
      glucose (3 g/kg BW0.75). Blood samples for glucose analyses were taken at -10,
      10, 20, 30, 40, 50, 60, 70, 80, 90, 105, and 120 min after glucose was fed. The
      supply of additional dietary starch or fat did not increase piglet birth weight
      or total litter weight at birth. Sows that were fed the high-NSP diet had more (P
      = 0.097) live-born piglets and fewer (P = 0.084) stillborn piglets than did sows
      that were fed additional fat, whereas sows that were fed additional starch were
      intermediate for these variables. Piglet mortality after birth was not affected
      by dietary treatment. Body weight and backfat gains in the last month of
      gestation were higher for sows fed additional starch or fat than for sows fed the
      high-NSP diet (P < 0.001 and P = 0.017, respectively). Feed intake in lactation
      was greatest by sows fed the high-NSP diet, least by sows fed additional starch
      at the end of gestation, and intermediate by sows fed additional fat (P = 0.099).
      The differences in lactation feed intake did not result in differences in BW and
      backfat losses during lactation. Sows that were fed additional fat had the
      greatest glucose area under the curve (P = 0.044), indicating that these sows
      were less tolerant to glucose. In conclusion, feeding additional energy (starch
      or fat) in late-gestating sows that are fed a high-NSP diet did not increase
      litter weight at birth or piglet survival, but did increase maternal gain.
      Feeding sows additional energy from fat might induce glucose intolerance, whereas
      feeding sows additional energy from starch did not induce glucose intolerance.

PMID- 15484949
TI  - A regional evaluation of chromium tripicolinate supplementation of diets fed to
      reproducing sows.
AB  - A cooperative research study involving 353 litters was conducted at three
      stations to determine the effects of graded levels of supplemental Cr from
      chromium tripicolinate (CrPic) on reproductive performance of sows and preweaning
      performance of their pigs. Primiparous and multiparous sows were fed fortified
      corn-soybean meal diets with supplemental levels of 0, 200, 600, or 1,000 ppb Cr
      (as-fed basis). Each station used at least three of the supplemental Cr levels,
      with two of those levels being 0 and 200 ppb. Station effects were observed for
      sow gestation weight gain, lactation weight change, lactation feed intake, litter
      size at birth and weaning, and pig weight at birth and weaning (P = 0.001 to
      0.087). Supplemental Cr increased the number of pigs born live per litter (9.49,
      9.82, 10.94, and 10.07; quadratic, P = 0.05) and sow lactation weight change (
      0.2, 0.8, -4.1, and -3.9 kg; linear, P = 0.01) but decreased individual birth
      weight of total pigs born (1.61, 1.57, 1.47, and 1.56 kg; quadratic, P = 0.10).
      Tissues were obtained from a subset of sows from one station after they had
      completed three parities on the study. The content of Cr in the adrenal gland
      (16.4, 20.0, 34.0, and 48.4 ppb), kidney (35.8, 56.4, 132.6, and 176.0 ppb), and
      liver (22.8, 37.4, 87.6, and 92.2 ppb) was increased linearly (P = 0.001 to
      0.005) by increasing CrPic supplementation. The results suggest that the
      supplementation level that maximizes the biological response is above that
      currently allowed. Additionally, supplementation of Cr at 1,000 ppb (five times
      currently permitted supplementation levels) was not detrimental to sow
      performance, even when fed continuously for three parities. There may be merit to
      continued research to evaluate higher supplementation rates.

PMID- 15484950
TI  - The effect of dietary fish oil supplementation on exercising horses.
AB  - Ten horses of Thoroughbred or Standardbred breeding were used to study the
      effects of dietary fish oil supplementation on the metabolic response to a high
      intensity incremental exercise test. Horses were assigned to either a fish oil (n
      = 6) or corn oil (n = 4) treatment. The fish oil (Omega Protein, Hammond, LA)
      contained 10.6% eicosapentaenoic acid and 8% docosahexaenoic acid. Each horse
      received timothy hay and a textured concentrate at a rate necessary to meet its
      energy needs. The supplemental oil was top-dressed on the concentrate daily at a
      rate of 324 mg/kg BW. Horses received their assigned diet for 63 d, during which
      time they were exercised 5 d/wk in a round pen or on a treadmill. During wk 1,
      horses exercised for 10 min at a trot. After wk 1, exercise time and intensity
      were increased so that at wk 5, exercise time in the round pen increased to 30
      min (10 min of cantering and 20 min of trotting) per day. Starting at wk 6,
      horses were exercised 3 d/wk in the round pen for 30 min and 2 d/wk on a
      treadmill for 20 min. After 63 d, all horses performed an exercise test
      consisting of a 5-min warm-up at 1.9 m/s, 0% grade, followed by a step test on a
      10% grade at incremental speeds of 2 to 8 m/s. Blood samples were taken
      throughout exercise. During exercise, horses receiving fish oil had a lower heart
      rate (treatment x time interaction; P < 0.05) and tended to have lower packed
      cell volume (treatment effect; P = 0.087). Plasma lactate concentrations were not
      affected by treatment. Plasma glucose concentrations were not different between
      groups during exercise but were lower (treatment x time interaction; P < 0.01)
      for the fish oil group during recovery. Serum insulin tended to be lower in fish
      oil horses throughout exercise (treatment effect; P = 0.064). There was a
      tendency for glucose:insulin ratios to be higher for fish oil-treated horses
      throughout exercise (treatment effect; P = 0.065). Plasma FFA were lower
      (treatment x time interaction; P < 0.01) in horses receiving fish oil than in
      horses receiving corn oil during the initial stages of the exercise test. Serum
      glycerol concentrations also were lower in fish oil-treated horses (P < 0.05).
      Serum cholesterol concentrations were lower in horses receiving fish oil
      (treatment effect; P < 0.05), but serum triglycerides were not affected by
      treatment (P = 0.55). These data suggest that addition of fish oil to the diet
      alters exercise metabolism in conditioned horses.

PMID- 15484951
TI  - Soybean oil supplementation of a high-concentrate diet does not affect site and
      extent of organic matter, starch, neutral detergent fiber, or nitrogen digestion,
      but influences both ruminal metabolism and intestinal flow of fatty acids in
      limit-fed lambs.
AB  - Our objective was to measure ruminal fermentation characteristics and site and
      extent of nutrient digestion in sheep limit-fed an 81.6% (DM basis) concentrate
      diet supplemented with increasing levels of soybean oil. Eight white-faced wether
      lambs (39.9+/-3.0 kg BW) fitted with ruminal, duodenal, and ileal cannulas were
      used in a replicated 4 x 4 Latin square experiment. Diets were formulated to
      contain 15.0% CP (DM basis) and included bromegrass hay (18.4%), cracked corn,
      soybean oil, corn gluten meal, urea, and limestone. Soybean oil was added to
      diets at 0, 3.2, 6.3, and 9.4% of dietary DM. The diet was limit-fed at 1.4% of
      BW. After 14 d of dietary adaptation, Cr2O3 (2.5 g) was dosed at each feeding for
      7 d followed by ruminal, duodenal, ileal, and fecal sample collections for 3 d.
      Digestibilities of OM, starch, NDF, and N were not affected (P = 0.13 to 0.95) by
      increasing dietary soybean oil level. Means for true ruminal (percentage of
      intake), lower-tract (percentage entering the duodenum), and total-tract
      (percentage of intake) digestibility for each nutrient were (mean+/-SEM): OM =
      50.7+/-4.66%, 71.6+/-2.58%, and 82.7+/-0.93%; starch = 92.0+/-1.94%, 96.1+/
      0.70%, and 99.8+/-0.05%; NDF = 36.7+/-6.75%, 50.9+/-7.58%, and 71.7+/-1.93%; and
      N = 31.6+/-9.93%, 84.1+/-1.50%, and 81.0+/-1.10%, respectively. Total VFA
      concentration was greatest in sheep fed 6.3% soybean oil and least in sheep fed
      9.4% soybean oil (cubic, P = 0.01). Duodenal flow of fatty acids from the diet
      and those metabolized within the rumen increased (linear, P < 0.001) with
      increasing dietary soybean oil level. Ileal flow of 16:0, 17:0, 18:0, 18:1trans,
      and 18:1cis-9 fatty acids increased (P < or = 0.04) with increasing dietary
      soybean oil level. Apparent small intestinal disappearance of 18:0 decreased
      (linear, P = 0.004) as dietary soybean oil increased, and with 9.4% dietary
      soybean oil, nearly half the duodenal 18:0 was observed at the ileum; thus, the
      true energy value of the soybean oil decreased with increasing oil
      supplementation. We conclude that supplementation of a high-concentrate diet with
      increasing amounts of soybean oil in limit-fed sheep resulted in a trade off
      between loss of potential dietary energy from the fat and gain of important PUFA
      and biohydrogenation intermediates, but without a marked influence on
      digestibility of other important macronutrients.

PMID- 15484952
TI  - Effect of Se on selenoprotein activity and thyroid hormone metabolism in beef and
      dairy cows and calves.
AB  - Although Se is essential for antioxidant and thyroid hormone function, factors
      influencing its requirement are not well understood. A survey and two experiments
      were conducted to determine the influence of cattle breed and age on
      selenoprotein activity and the effect of maternal Se supplementation on cow and
      calf selenoprotein activity and neonatal thyroid hormone production. In our
      survey, four cowherds of different ages representing three breeds were bled to
      determine the influence of breed and age on erythrocyte glutathione peroxidase
      activity (RBC GPX-1). All females were nonlactating, pregnant, and consumed total
      mixed diets (Holstein) or grazed pasture (Angus and Hereford). In our survey of
      beef breeds, yearlings had greater average RBC GPX-1 activity than mature cows.
      In Exp. 1, neonatal Holstein heifers (n = 8) were bled daily from 0 to 6 d of age
      to determine thyroid hormone profile. An injection of Se and vitamin E (BO-SE)
      was given after the initial bleeding. Thyroxine (T4) and triiodothyronine (T3)
      concentrations were greatest on d 0 and decreased (P < 0.05) continuously until d
      5 postpartum (156.13 to 65.88 and 6.69 to 1.95 nmol/L, d 0 to 5 for T4 and T3,
      respectively). Reverse T3 concentrations were 3.1 nmol/L on d 0 and decreased (P
      < 0.05) to 0.52 nmol/ L by d 5. In Exp. 2, multiparous Hereford cows were
      drenched weekly with either a placebo containing 10 mL of double-deionized H2O (n
      = 14) or 20 mg of Se as sodium selenite (n = 13). After 2 mo of treatment, Se
      drenched cows had greater (P < 0.01) plasma concentrations than control cows
      (84.92 vs. 67.08 ng/mL), and at parturition, they had plasma Se concentrations
      twofold greater than (P < 0.05) control cows (95.51 vs. 47.14 ng Se/mL). After 4
      mo, cows receiving Se had greater (P < 0.05) RBC GPX-1 activity than controls;
      this trend continued until parturition. Colostrum Se concentration was twofold
      greater (P < 0.05) in Se-drenched cows than control cows (169.97 vs. 87.00
      ng/mL). Calves born to cows drenched with Se had greater (P < 0.05) plasma Se
      concentration, RBC GPX-1, and plasma glutathione peroxidase activity on d 0
      compared with calves born to control cows. By d 7, no differences in plasma
      glutathione peroxidase activity in calves were observed. Maternal Se
      supplementation did not influence calf thyroid hormone concentrations. Selenium
      provided by salt and forages is not adequate for cattle in Se-deficient states.

PMID- 15484953
TI  - Ruminal fermentation and degradation patterns, protozoa population and urinary
      purine derivatives excretion in goats and wethers fed diets based on olive
      leaves.
AB  - Olives leaves, accrued during the processing of olive harvests for oil
      extraction, are poor in N, rich in crude fat and ADF (1.19, 8.03 and 28.2 g/100 g
      of DM, respectively), and relatively low in condensed tannins (11.1 mg/g of DM).
      Three experiments were conducted in a 2 x 3 (two animal species: goats vs.
      wethers; and three experimental diets: olive leaves without or with polyethylene
      glycol supply and olive leaves supplemented with barley and faba beans) factorial
      design to evaluate ruminal degradation and passage kinetics (Exp. 1),
      fermentation pattern and protozoa population (Exp. 2), and urinary purine
      derivatives excretion (Exp. 3). Polyethylene glycol was supplied to evaluate the
      effects of condensed tannins contained in olive leaves. Ruminal degradability of
      CP was low in both goats and wethers, although goats showed higher (P < 0.05)
      values than wethers. Supplementation of olive leaves with barley and faba beans
      increased (P < 0.001) ruminal degradability of DM and CP. Both goats and wethers
      fed olive leaves showed similarly low particulate fractional passage rates (0.021
      and 0.023/h, respectively). Ingestion of olive leaves promoted low NH3-N and VFA
      concentrations, which reflect poor microbial activity. These concentrations,
      especially that of VFA, increased when barley and faba beans were added.
      Ingestion of olive leaves affected ruminal protozoa: Entodiniomorphida showed low
      concentrations and Holotricha completely disappeared. When animals received a
      diet based on olive leaves, barley, and faba beans, Holotricha appeared in the
      ruminal liquor and Entodiniomorphida increased (P < 0.001). In goats and wethers
      fed olive leaves alone, urinary allantoin excretion was very low (163 and 164
      micromol/kg BW0.75 in goats and wethers, respectively), and moderate values (352
      and 389 micromol/kg BW0.75 in goats and wethers, respectively) were observed when
      a diet of olive leaves, barley, and faba beans was fed. The polyethylene glycol
      supply did not have an effect in goats or in wethers, indicating the lack of an
      effect of condensed tannins in olive leaves. Ingestion of olive leaves promotes a
      low microbial activity, although its supplementation with readily degraded
      carbohydrates and protein improves microbial activity and, as a consequence,
      increases its ruminal degradation. In general, for most of the measured
      variables, there were no animal species x diet interactions. Thus, goats and
      wethers had similar ruminal activities when fed diets based on olive leaves.

PMID- 15484954
TI  - Influence of abomasal carbohydrates on small intestinal sodium-dependent glucose
      cotransporter activity and abundance in steers.
AB  - Most animals adapt readily to increased supplies of carbohydrate in the
      intestinal lumen by increasing enzymes for degradation and increasing glucose
      transporter activity. However, the extent of upregulation of Na+-dependent
      glucose cotransporter 1 (SGLT1) activity and content in response to increased
      delivery of carbohydrate to the small intestinal lumen of ruminants is unclear.
      Therefore, an experiment was conducted to determine the effect of glucose and
      starch hydrolysate on the activity and abundance of SGLT1 in the small intestine
      of steers. In a randomized complete block design, 40 crossbred beef steers (243+/
      2 kg BW) were fed 0.163 Mcal of ME/(kg BW0.75(d; W), 0.215 Mcal of ME/(kg BW0.75
      x d; 2M), or 0.163 Mcal ME/(kg BW0.75 x d) and infused for 35 d into the rumen
      (R) or abomasum (A) with 12.6 g/(kg BW0.75 x d) of starch hydrolysate (S) or into
      the abomasum with 14.4 g/(kg BW0.75 x d) of glucose (G). Steers were slaughtered,
      and brush-border membrane vesicles were prepared from the small intestinal
      samples obtained from five equidistant sites along the intestine. Maltase
      activity in vesicles and homogenates differed with intestinal sampling site
      (quadratic, P < 0.001). Steers on the AG treatment yielded a greater intestinal
      maltase activity (38 nmol glucose x mg protein(-1) x min(-1)) compared with the
      AS, RS, W, or 2M treatments (34, 26, 23, and 23 nmol glucose x mg protein(-1) x
      min(-1) respectively [SEM = 3; P = 0.02]). Sodium-dependent glucose uptake
      averaged 18.4+/-3.94 pmol glucose/(mg protein x s) and was not affected by
      treatment, but uptake decreased distally along the intestine (P < 0.001). There
      was no effect of treatment on SGLT1 protein abundance, but SGLT1 protein
      abundance increased linearly from the duodenum to the ileum (P = 0.05). The
      inverse relationship between glucose uptake and SGLT1 abundance suggests that the
      regulation of brush border Na+-dependent glucose transport capacity is complex,
      involving factors other than the presence of luminal carbohydrate.

PMID- 15484955
TI  - Effect of dietary restriction, pregnancy, and fetal type on intestinal
      cellularity and vascularity in Columbia and Romanov ewes.
AB  - The objectives of this study were to evaluate intestinal cellularity and
      vascularity in mature ewes in response to dietary restriction and pregnancy
      status and to quantify the response of these variables to increased nutrient
      demand of fetal growth. In Exp. 1, 28 mature Dorset x crossbred white-faced ewes
      (61.6+/-1.8 kg initial BW) were fed a pelleted, forage-based diet. Treatments
      were arranged in a 2 x 3 factorial, with dietary restriction (60% restriction vs.
      100% maintenance for respective states of pregnancy) and pregnancy status
      (nonpregnant, NP; d 90 and 130) as main effects. Dietary treatments were
      initiated on d 50 of gestation and remained at 60 or 100% maintenance throughout
      the experiment. Nonpregnant ewes were fed dietary treatments for 40 d. In Exp. 2,
      four Romanov ewes were naturally serviced (Romanov fetus and Romanov dam; R/R);
      two Romanov embryos per recipient were transferred to four Columbia recipients
      (Romanov fetus and Columbia recipient; R/C), and three Columbia ewes were
      naturally serviced (Columbia fetus and Columbia dam; C/C). In Exp. 1, dietary
      restriction and pregnancy status interacted with regard to maternal jejunal DNA
      concentration (P < 0.01), with restricted ewes having a greater DNA concentration
      (mg/g; fresh basis) at d 130. Vascularity (percentage of total tissue area) in
      the jejunum was increased (P < 0.06) as a result of dietary restriction and
      pregnancy status. Total microvascular volume ofjejunal tissue was not altered by
      dietary restriction and increased (P < 0.01) at d 130 of pregnancy. In Exp. 2,
      R/R ewes had less (P < 0.09) DNA (g) in the jejunum compared with R/C and C/C
      ewes. Jejunal vascularity (%) was increased (P < 0.05) in R/R ewes compared with
      R/C or C/C ewes, whereas total jejunal microvascular volume remained unchanged.
      These data demonstrate intestinal vascular density responds to changes in diet
      and physiological state. In addition, pregnancy increased total jejunal
      microvascular volume.

PMID- 15484956
TI  - The effects of the antioxidant lipoic acid on beef longissimus bloom time.
AB  - The objective of this study was to evaluate the influence of lipoic acid (LA) on
      beef LM steak bloom time, as well-as to characterize bloom time in the CIE L*,
      a*, and b* color space over a 93-min period. Thirty-two Simmental steers were
      supplemented with LA for 21 d immediately before slaughter at levels of 0, 8, 16,
      or 24 mg of LA/kg BW (eight steers per treatment). Lipoic acid was mixed with
      liquid paraffin, allowed to solidify, prilled, and top-dressed over a standard
      finishing diet. Steers were slaughtered at the University of Missouri abattoir in
      four groups of eight (two steers per treatment) over a 2-wk period. After a 24-h
      chill at 4 degrees C, the right LM was removed from each carcass. One 2.54cm
      steak was removed from the anterior portion of the LM, and its color
      characteristics (CIE L*, a*, and b*) were measured immediately with a
      standardized spectrocolorimeter. Color measurements were taken every 3 min
      thereafter for a total of 93-min. Hue angle (true red) and chroma (color
      saturation) were calculated from the color measurements. Addition of LA to the
      diet had no effect on bloom time (P = 0.67). When treatment means were analyzed,
      the addition of 24 mg of LA/kg BW to the diet resulted in higher (lighter) L*
      values (P < 0.05) compared with other treatments, whereas the addition of 16 mg
      of LA/kg BW to the diet caused lower hue angles (more true red; P < 0.05) when
      compared with other treatments. Addition of LA to the diet did not affect a* (P =
      0.13) and b* (P = 0.18) values or chroma (P = 0.62). In the absence of treatment
      effects, bloom times for all treatments were pooled, and L* values did not change
      (P > 0.05) during the 93-min bloom time; however, a* and chroma values increased
      for 9 min and plateaued after 12 min (P < 0.01). Similarly, b* values increased
      (P < 0.01) for the first 6 min, and after 9 min, no further increase in
      yellowness was detected. Bloom time had little effect on hue angle, which
      stabilized after 3 min. Supplementing steers with the antioxidant LA for 21 d had
      no effect on the bloom time of beef LM; however, higher levels of supplemental LA
      affected L* values and hue angles of beef.

PMID- 15484957
TI  - Growing and finishing performance of steers when fed recycled poultry bedding
      during the growing period.
AB  - Sixty Angus-cross steers were used to compare the effects of recycled poultry
      bedding (RPB) stacking method and the inclusion of monensin in growing diets on
      performance. Steers were individually fed balanced, growing diets for a period of
      84 d. The diets were control (CON), CON + monensin (CON+M), deep-stacked RPB
      (DS), DS+M, shallow-stacked RPB (SS), and SS+M. The CON diets contained corn,
      soybean meal, corn silage, and cottonseed hulls. In the RPB diets, 35% of the
      silage, cottonseed hulls, and soybean meal was replaced with RPB (as-fed basis).
      At the end of the growing period, 30 steers, representing all treatment groups,
      had liver biopsies for trace mineral analysis and ruminal fluid samples to assess
      pH, VFA, and ammonia concentrations. All steers had blood samples drawn at the
      end of the growing period for analysis of Se and urea N. Steers were transported
      466.6 km to simulate shipping stress and started on a finishing diet for a 120-d
      period. Intake, ADG, and G:F were monitored throughout the trial. Steers fed CON
      diets had higher ADG, DMI, and G:F than SS, and higher ADG and G:F than DS (P <
      0.05) during the growing period. Steers fed DS diets had higher DMI than SS (P <
      0.05) during the growing period. Inclusion of monensin in the growing diets
      increased G:F and decreased DMI (P < 0.05). Steers from the RPB treatments
      started the finishing period at lighter BW than steers fed CON diets (P < 0.05).
      During the finishing period, steers fed SS diets had higher DMI than steers fed
      CON diets (P < 0.06), whereas steers fed DS diets were intermediate. At
      slaughter, steers fed CON diets had higher hot carcass weights and quality grades
      than steers fed SS diets (P < 0.07), whereas steers fed DS diets were
      intermediate. Results indicate that steers fed RPB consumed it better when
      processed by deep stacking before consumption, that carryover effects of RPB into
      the finishing phase were minimal, and inclusion of monensin did not affect
      consumption of RPB diets.

PMID- 15484958
TI  - Use of pet food-grade poultry by-product meal as an alternate protein source in
      weanling pig diets.
AB  - Three experiments were conducted to evaluate pet food-grade poultry by-product
      meal (PBM) as a replacement protein source for fish meal (FM), blood meal (BM),
      and spray-dried plasma protein (SDPP) in weanling pig diets. In the first study,
      200 crossbred pigs (initial BW = 6.5 kg) were weaned (21 d) and randomly allotted
      to one of four dietary treatments, which included a control and three test diets
      where PBM was substituted for FM, blood products, or both. Experimental diets
      were fed during Phase I (d 0 to 5 postweaning) and Phase II (d 5 to 19), and a
      common Phase III diet was fed from d 19 to 26. Overall (d 0 to 26), there was no
      difference in performance of pigs fed PBM in place of the other ingredients.
      However, during Phase I, BW (P < 0.05), ADG (P < 0.02), and intake (P < 0.001) in
      pigs fed diets containing SDPP were greater than those fed diets with PBM. In
      Exp. 2, the performance of pigs (n = 100, initial BW = 6.5 kg) fed diets
      containing 20% PBM (as-fed basis, replacing SDPP, BM, FM, and a portion of the
      soybean meal) in all phases of the nursery diet was compared with a group fed
      conventional diets without PBM. There were no differences in overall performance
      (d 0 to 26); however, ADG (P < 0.10) and feed intake were higher (P < 0.01) for
      pigs fed the conventional diet than for pigs fed the 20% PBM diet during Phase I
      (d 0 to 5). Experiment 3 was a slope-ratio assay to determine the ability of PBM
      to replace SDPP. A total of 320 pigs (initial BW = 7.32 kg) was weaned (21 d) and
      allotted to five treatment groups in three trials in a blocked design with
      product (SDPP or PBM) as the first factor, and lysine level (1.08, 1.28, 1.49%;
      as-fed basis) as the second factor. Growth rate increased with increasing lysine
      (P < 0.05), regardless of the source. These results indicate that PBM can be used
      in nursery diets in place of blood meal and fish meal without affecting
      performance. Furthermore, although feeding PBM in Phase I diets was not
      equivalent to SDPP during the first week, there was no overall difference in
      performance at the end of the nursery phase.

PMID- 15484959
TI  - Comparison of three methods of feeding sows in gestation and the subsequent
      effects on lactation performance.
AB  - A total of 684 sows from breeding groups over 6 wk was used to compare three
      methods of feeding during gestation on gestation and lactation performance.
      Control gilts and sows were fed according to body condition based on a scale of 1
      to 5 (1 = thin, 5 = fat). Sows were visually assessed for body condition at
      breeding and were assigned a daily feed allowance to achieve a BCS of 3 at
      farrowing. Treatment 2 used feeding levels based on backfat thickness (measured
      between d 0 and 5 after breeding) and weight at weaning for sows or service for
      gilts. Feed allowance was calculated to achieve a target backfat of 19 mm at
      farrowing, and remained constant from d 0 to 101 of gestation. Feed allowances
      were based on modeled calculations of energy and nutrient requirements to achieve
      target sow maternal weight and backfat gains. Treatment 3 was identical to
      Treatment 2, except that feeding pattern was altered for thin sows and gilts (<15
      mm at service) in an attempt to reach 19 mm by d 36 of gestation. Sows were
      weighed at the previous weaning, and gilts were weighed at service, with both
      weighed again between d 112 and 114 of gestation. Backfat was measured between d
      0 and 5, and again between d 108 and 113 of gestation. At farrowing, sows on
      Treatments 2 and 3 had 19 and 19.1 mm of backfat, respectively, whereas control
      sows tended to have greater (P < 0.07) backfat (20 mm). On average, sows targeted
      to gain 6 to 9 mm of backfat failed to reach target gains regardless of feeding
      method. Feeding sows in gestation based on backfat (Treatments 2 and 3) resulted
      in a numerically higher proportion of sows in the target backfat range of 17 to
      21 mm (40.2, 53.3, and 52.6% for control and Treatments 2 and 3, respectively) at
      farrowing and a numerically lower percentage of fat sows (>21 mm), but no
      difference in the percentage of thin sows (<17 mm) compared with feeding based on
      body condition. In conjunction with this observation, sows fed based on BCS were
      fed higher (P < 0.05) feeding levels in gestation than were sows fed based on
      backfat depth. Gestation feeding method had no effect on performance during
      lactation. Feed intake in lactation was lower (P < 0.05) for high backfat sows
      (>21 mm) at farrowing compared with sows with <21 mm. The high proportion of sows
      in the optimal backfat category demonstrates that feeding based on backfat and BW
      has potential for facilitating more precise feeding during gestation.

PMID- 15484960
TI  - Methods to reduce or eliminate detection of estrus in a melengestrol acetate
      PGF2alpha protocol for synchronization of estrus in beef heifers.
AB  - Three experiments were conducted to evaluate methods to decrease or eliminate the
      detection of estrus inherent to a melengestrol acetate (MGA)-PGF2alpha (PGF)
      protocol for synchronization of estrus in heifers. In each experiment, all
      heifers received 0.5 mg of MGA x animal(-1) x d(-1) for 14 d (d -32 to -19) and
      PGF (25 mg, i.m.; d 0, 0 h) 19 d after the last feeding of MGA (MGA-PGF
      protocol). In Exp. 1, heifers (n = 709) were assigned to each of the following
      protocols: 1) the MGA-PGF protocol with AI 6 to 12 h after detection of estrus
      (estrus AI; MGA-PGF); 2) MGA-PGF plus 100 microg, i.m. of GnRH on d -7 (1x GnRH)
      and estrus AI; or 3) MGA-PGF, GnRH on d -7, and GnRH (100 microg, i.m.) at 48 h
      after PGF, coincident with insemination (2x GnRH-TB48). In Exp. 2, heifers (n =
      559) received the MGA-PGF protocol and were inseminated by either estrus AI or
      fixed-time AI (TAI) at 60 h, coincident with an injection of GnRH (GnRH-TB60). In
      Exp. 3, all heifers (n = 460) received the MGA-PGF protocol and were inseminated
      by estrus AI when detected up to 73 h. Heifers not observed in estrus by 73 h
      received TAI between 76 and 80 h. Half the heifers inseminated by TAI received no
      further treatment (TB80), and the remaining half was injected with GnRH at
      insemination (GnRH-TB80). Variance associated with the interval to estrus and the
      proportion in estrus from d 0 to 5 was similar for 1x GnRH and MGA-PGF treatments
      in Exp. 1. Pregnancy rate (d 0 to 5) did not differ for the MGA-PGF and 1x GnRH
      treatments (62.5 and 60.4%, respectively), and both were greater (P < 0.05) than
      TAI pregnancy rate in the 2x GnRH-TB48 treatment (42.3%). In Exp. 2, the peak
      estrous response occurred 60 h after PGF. Pregnancy rate during the synchrony
      period was greater (P < 0.05) for the MGA-PGF (255/401; 63.6%) than the GnRH-TB60
      (74/158; 46.6%) treatment. In Exp. 3, 75.7% of heifers (348/460) were detected in
      estrus by 73 h and were inseminated, with a conception rate of 74.4%. Pregnancy
      rates after TAI did not differ between TB80 and GnRH-TB80 (14/56 = 25% and 19/ 56
      = 33.9%, respectively). Total pregnancy rate was 63.5% for heifers inseminated
      after detected estrus and by TAI. Collectively, these data indicate that the
      exclusive use of TAI for heifers treated with the MGA-PGF protocol resulted in
      lower pregnancy rates than when AI was performed after detection of estrus.
      However, estrus AI for 3 d and TAI at the end of d 3 could result in pregnancy
      rates similar to those achieved after a 5-d period of detecting estrus.

PMID- 15484961
TI  - Effect of management strategies on reducing heat stress of feedlot cattle: feed
      and water intake.
AB  - Three experiments were conducted to evaluate management strategies designed to
      decrease heat stress of cattle finished during the summer. In Exp. 1, 144 Angus
      crossbred yearling steers were assigned to three treatments: 1) ad libitum access
      to feed at 0800 (ADLIB); 2) fed at 1600 with feed amount adjusted so that no feed
      was available at 0800 (BKMGT); and 3) fed at 1600 at 85% of predicted ad libitum
      levels (LIMFD). Treatments were imposed for 23 d of an 82-d study, after which
      all steers were fed ad libitum at 0800. Treatment did not affect (P > 0.10)
      overall DMI, although ADLIB cattle tended to consume less feed. Overall water
      intake was decreased (P < 0.05) by 6.8 L x animal(-1) x d(-1) for LIMFD vs. ADLIB
      steers. In Exp. 2, 96 Angus crossbred yearling steers were assigned to three
      treatments: 1) control, no water application; 2) water applied to the pen
      surfaces between 1000 and 1200 (AM); and 3) water applied to pen surfaces between
      1400 and 1600 (PM). Water intake and DMI did not differ among treatments;
      however, feed efficiency of AM steers was superior (P = 0.06) to that of PM
      steers. Conversely, marbling scores of PM steers were higher (P = 0.06) than
      those of AM steers. In Exp. 3, 192 crossbred steers were used to determine the
      effects of feeding time (0800 [AMF] vs. 1400 [PMF]), with (WET) and without (DRY)
      sprinkling (20 min every 1.5 h between 1000 and 1750). Feed DMI did not differ
      among treatments; however, water intake and marbling scores were highest (P <
      0.05) for AMF/DRY steers. During these experiments, bunk scores (0 = <10% of feed
      delivered remaining; 1 = 10 to 50% of feed remaining; 2 = >50% of feed remaining)
      were assigned to each pen at various times during the day. In Exp. 1, bunk scores
      of BKMGT pens remained similar (P > 0.20) under varying environmental conditions,
      whereas LIMFD steers had lower scores (P < 0.05) as days on feed increased, even
      under hot environmental conditions. In Exp. 3, bunk scores of PMF/WET steers
      tended to be lower (P < 0.10) at 1700 and 2000 compared with PMF/ DRY pens under
      mild heat stress but not under severe heat stress. Alternative feeding regimens
      and sprinkling can alter the feed intake pattern of steers. Heat stress
      management strategies imposed in these experiments had minimal effects on cattle
      performance. Such strategies would be most useful for decreasing the
      susceptibility of cattle to hyperthermia and reducing related feedlot cattle
      deaths without adversely affecting performance.

PMID- 15484962
TI  - Effect of housing system and boar exposure on estrus expression in weaned sows.
AB  - Reproductive efficiency depends on detection of estrus, which may be influenced
      by housing and boar exposure. This experiment investigated the effects of housing
      system and boar contact on measures of estrus in weaned sows. Mixed-parity sows
      were randomly assigned to be weaned into gestation crates away from boars (AWC, n
      = 45), into pens away from boars (AWP, n = 42), or into pens adjacent to a mature
      boar (ADJ, n = 46). Estrus detection was initiated at approximately 0700 (0 h)
      and again at 0.25-, 0.5-, 1-, 2-, 4-, and 8-h intervals beginning on d 4 and
      continuing through d 7 following weaning. Estrus detection involved observation
      of the standing response after application of nose-to-nose boar exposure,
      backpressure, and side rubbing. For the AWC sows, a mature boar was moved to the
      front of the crates for a 10-min period and then removed. Sows housed in AWP were
      moved approximately 15 m to an empty pen adjacent to a mature boar for a 10-min
      period, and then returned to their pen. Sows housed ADJ were not moved and estrus
      detection was performed in their home pen for a 10-min period. The proportion of
      sows expressing estrus within 7 d from weaning was lowest for ADJ (80%, 37/46)
      compared with AWP (98%, 41/42) and AWC (96%, 43/45; P < 0.05). There was an
      effect of interval from weaning to estrus on the percentage of sows expressing
      estrus, but there was no interaction with treatment. Sows in AWC and AWP (4.7 d)
      had decreased (P = 0.01) intervals from weaning to estrus compared with ADJ (5.2
      d). The duration of estrus was also shorter (P < 0.001) for ADJ (45 h) compared
      with AWC (58 h) or AWP (62 h). There was a treatment x interval x day of estrus
      effect for the percentage of sows expressing estrus. After detection of the first
      standing response on the first day of estrus, only 62 to 82% of sows were
      detected standing over the next 2 h for all treatments. However, at 4 to 8 h,
      this increased to 85 to 98% for the AWC and AWP sows, but <73% of the ADJ sows
      were detected during this period. On the second day of estrus, estrus expression
      was not influenced by interval for the AWC and AWP sows and was between 90 to
      100% during the 8-h period, whereas ADJ sow detection rates were between 68 to
      88%. These data suggest that housing sows adjacent to boars negatively affects
      estrus expression and detection. In addition, refractory behavior occurs in
      approximately 30 to 40% of sows and is influenced by housing relative to the
      boar, day of estrus, and interval from last boar exposure.

PMID- 15484963
TI  - Comparison of target breeding weight and breeding date for replacement beef
      heifers and effects on subsequent reproduction and calf performance.
AB  - A 3-yr study was conducted with spring-born heifers (n = 240) to determine the
      effects of developing heifers to either 55 or 60% of mature BW at breeding on
      reproduction and calf production responses. A concurrent study was also conducted
      with summer-born heifers (n = 146) to examine effects of breeding heifers with
      the mature cow herd or 1 mo earlier on reproduction and calf production
      variables. Spring-born crossbred heifer calves were weaned and developed on two
      different levels of nutrition to achieve the desired prebreeding BW. Summer-born
      heifers were developed to similar target breeding BW (60% of mature BW) to begin
      calving either 1 mo before (May) or at the same time as the mature cowherd
      (June). Blood samples were taken before breeding to determine differences in
      estrous cyclicity. Pregnancy rates through the fourth pregnancy were determined.
      Cow and calf production variables were evaluated through the third gestation.
      Spring-born heifers reached 53 or 58% of mature BW at breeding and had similar
      reproduction and first calf production traits between the two, groups. Calving
      difficulty with the second calf was greater (P < 0.05) for heifers developed to
      58% of mature BW at breeding. Subsequent second calf weaning weight and ADG were
      decreased (P < 0.05) for heifers developed to 58% of mature BW at breeding. Feed
      costs were $22/heifer less for heifers developed to 53% of mature BW. Summer-born
      first-calf heifers calving in June had less (P < 0.01) calving difficulty than
      did heifers calving in May; however, calf birth weights were similar. Breeding
      summer-born heifers 1 mo before the cowherd did not influence pregnancy rates
      over three calf crops; however, first calf adjusted weaning weights and ADG were
      greater for calves born earlier. Development costs were $11/heifer more for
      heifers developed to calve in May vs. June. Developing spring-born heifers to 53%
      of mature BW did not adversely affect reproduction or calf production traits
      compared with developing heifers to 58% of mature BW, and it decreased
      development costs. Breeding summer-born heifers before the cowherd increased
      heifer development costs, increased calving difficulty, and improved calf
      performance, but had no effect on pregnancy rates.

PMID- 15484964
TI  - Conditioning cattle to graze broom snakeweed (Gutierrezia sarothrae).
AB  - Broom snakeweed (Gutierrezia sarothrae) is the most widespread range weed in
      North America. We attempted to positively condition cattle to graze broom
      snakeweed to create a biological tool to decrease the competitive ability of
      snakeweed in a plant community. Fifteen yearling heifers were divided into three
      treatment groups receiving different supplements: 1) cornstarch, 2) starch with
      ground snakeweed, and 3) a control (no supplements). Heifers were fed fresh
      snakeweed, and then were gavaged with the respective supplements to provide
      positive feedback to enhance their acceptance of snakeweed. The starch group
      consumed more snakeweed in the pen conditioning trial (P = 0.02). The starch and
      control groups were then taken to the field for two grazing trials. In the spring
      grazing trial, there was no snakeweed consumed in the free-ranging part of the
      trial; however, when the pasture size was decreased, the heifers started to
      consume snakeweed as alternative forages became less abundant. In the second
      small pasture trial, heifers in the positively conditioned group consumed more
      snake-weed than those in the control group (16 vs. 5% of bites, P < 0.001). In
      the fall grazing trial, little snakeweed was consumed in the free-ranging part of
      the trial. When the pasture size was decreased, both positively conditioned and
      control groups increased snakeweed consumption up to 35% of bites. In the small
      pastures of both the spring and fall grazing trials, 36 to 59% of snakeweed
      plants were grazed. Cattle can be forced to graze snake-weed in a short-duration,
      high-intensity grazing strategy.

PMID- 15484965
TI  - "Change yourself and the whole world will become kinder": Russian activists for
      reproductive health and the limits of claims making for women.
AB  - This article views reproductive health activism as a fruitful site for analyzing
      the cultural logics through which legitimate claims for women's needs become
      expressed and circumscribed. It begins from the observation that in the United
      States and Britain, reproductive health has been a key arena for feminist
      political claims and struggles for women's rights, bodily integrity, access to
      health care, and demands for authority in relations with experts. These concerns
      and struggles have not, however, emerged in all postsocialist contexts, and new
      activism in Russia reveals strikingly different agendas. Innovative groups of
      health providers seeking to increase women's access to birth control methods and
      safe sex, home birth opportunities, and improved health services work outside of
      feminist perspectives and reject political paths for change. By examining the
      ideological inspirations, cultural logics, and political-economic constraints
      shaping the outreach work of Russian health practitioners, the article explains
      how and why health activism became a site for personal "spiritual" revival and
      the strengthening of nuclear families. It also explores how conditions following
      the collapse of socialism have further legitimized activists' rejection of
      political agendas for change.

PMID- 15484966
TI  - Smoking as a weight-control strategy among adolescent girls and young women: a
      reconsideration.
AB  - Many studies have reported that adolescent girls and young women smoke to control
      their weight. The majority of these studies are cross-sectional and report on
      correlational data from quantitative surveys. This article presents data from
      ethnographic interviews with 60 smokers, interviewed in high school and in follow
      up interviews at age 21. Contrary to previous research, this study found little
      evidence for the sustained use of smoking as a weight-control strategy. In high
      school, smokers were no more likely than nonsmokers to be trying to lose weight.
      In the follow-up study, 85 percent of informants replied that they had never
      smoked as a way to control their weight. One-half of informants at age 21
      believed that smoking as a weight-control strategy would be ineffective, while
      the other one-half had no idea whether it would work or not. Researchers need to
      exert caution in propagating the idea that smoking is commonly used as a
      conscious and sustained weight-control strategy among adolescent females and
      young women.

PMID- 15484967
TI  - Thick prescriptions: toward an interpretation of pharmaceutical sales practices.
AB  - Anthropologists of medicine and science are increasingly studying all aspects of
      pharmaceutical industry practices--from research and development to the marketing
      of prescription drugs. This article ethnographically explores one particular
      stage in the life cycle of pharmaceuticals: sales and marketing. Drawing on a
      range of sources-investigative journalism, medical ethics, and autoethnography-
      the author examines the day-to-day activities of pharmaceutical salespersons, or
      drug reps, during the 1990s. He describes in detail the pharmaceutical gift
      cycle, a three-way exchange network between doctors, salespersons, and patients
      and how this process of exchange is currently in a state of involution. This gift
      economy exists to generate prescriptions (scripts) and can mask and/or perpetuate
      risks and side effects for patients. With implications of pharmaceutical industry
      practices impacting everything from the personal-psychological to the global
      political economy, medical anthropologists can play a lead role in the emerging
      scholarly discourse concerned with critical pharmaceutical studies.

PMID- 15484968
TI  - Madness, fear, and control in Bangladesh: clashing bodies of power/knowledge.
AB  - This article presents an understanding of how Bangladeshis cope with madness in
      relation to two assumptions: that systems of knowledge and of power are
      coterminous, and that actors in medical encounters draw on incompatible and
      unequal bodies of knowledge-power I first offer a perspective on psychiatry,
      emotion, and discourse in Bangladesh as a society increasingly caught up in
      globalizing modernity. Then I present two types of data to illumine tensions
      between various attempts to control the fears associated with schizophrenia. The
      first is a set of exchanges in the advice column of a new popular psychiatry
      magazine in Bangladesh that inculcate new perspectives on self Those who write to
      the editors signal their fears of what might, in the end, be impossible to
      control. Answers from the psychiatrists who edit the magazine reflect discourses
      circulating on the web, at international conferences, and at the institutions in
      the United Kingdom and the United States where one of them received his training.
      The second data set consists of video recordings of persons diagnosed with
      schizophrenia interacting with families and/or psychiatrists. In part because of
      knowledge-power asymmetries, attempts at controlling fears surrounding
      schizophrenia in these four cases fail to address the depths, tacitness,
      embodiment, and narrative embedding of anxieties experienced by all parties. I
      close with an argument about the implications for theories of culture and of
      medical pluralism that arise from cases in which the local Self is experienced
      from the perspective of powerful Others.

PMID- 15484969
TI  - Embodied changes and the search for gynecological cancer diagnosis.
AB  - The detection and successful treatment of cancers is dependent on timely
      presentation with abnormal and often subtle symptoms. In this article, we draw on
      research conducted with Australian immigrant women in 2001-02 who experienced
      delays in diagnosis of gynecological cancer. Data from in-depth interviews with
      women with gynecological cancer indicated a common trajectory of an "illness
      career" whereby the search for diagnosis was often painful and lengthy, either
      because women normalized the abnormal signs or because their experiences of
      bodily abnormality, pain, and dysfunction contrasted with medical explanations.
      This delay was sometimes exacerbated by structural barriers. As a result,
      diagnosis was often protracted, during which time women presented with symptoms
      that were dismissed or resulted in the misdiagnosis, with a resultant loss of
      confidence in clinical services.

PMID- 15484971
TI  - [Fatal tropical malaria in Russian citizens who traveled to countries with a
      tropical climate].

PMID- 15484970
TI  - [Water and intestinal parasitic diseases].
AB  - The paper presents data on the rates of Lamblia cyst dissemination of surface
      water sources in foreign countries, the Russian Federation, Moscow, and the
      Moscow Region. It shows a role of drinking water in the spread of intestinal
      parasitic diseases. In accordance with parasitological parameters, specific data
      on improvement of methodological control of water quality are presented. The
      dosages of ultraviolet radiation are given in relation to water decontamination
      of parasitic disease germs.

PMID- 15484972
TI  - [European region program--"Roll Back Malaria": its results and prospects for its
      control].
AB  - The WHO has committed itself to an intensive response to the burden of malaria
      and, by 1999, had developed a regional strategy as to Roll Back Malaria (RBM)
      program in the affected countries of the European Region. This strategy is
      presently being implemented on the ground. Malaria was on the agenda of the
      recent 52nd Session of the Regional Committee for Europe; and the regional
      resolution "Scaling up the response to malaria in the WHO European Region" was
      endorsed by all member states. This paper discusses the progress with RBM in the
      region and the results achieved and challenges to be addressed in the years
      ahead.

PMID- 15484973
TI  - [Supplement to the list of Anopheles (Diptera, Culicidae) mosquitoes of
      Tadjikistan and the predominant types of vectors in the current foci of malaria
      in the republic].
AB  - The species composition of and the indices of predominance of Anopheles
      mosquitoes were determined in the current foci of malaria in the Republic of
      Tadjikistan. The predominant types of malaria mosquitoes were An. superpictus,
      An. pulcherrimus, and An. hypcanus were found to be in the Khatlon Region of
      Tadjikistan and in the contiguous areas of Uzbekistan. An. superpictus prevailed
      in the study foci of malaria and, as An. pulcherrimus, were the most dangerous
      vectors of malaria in the south of the republic. The main vectors of malaria were
      shown to be An. maculipennis sensu stricto and An. superpictus in the environs of
      the town of Khudjand, Sogdi Region (Tadjikistan). An. maculipennis was first
      recorded for Tadjikistan and should be included into the list of malaria
      mosquitoes of the republic. It is suggested that An. pulcherrimus plays an
      important role in the spread of malaria in the north of Tadjikistan.

PMID- 15484974
TI  - [Peter-the-Great Gulf fishes are a source of human invasion of the nematode
      Anisakis simplex (the family Anisakidae)].
AB  - The paper presents the results of the rate of infection with the nematode
      Anisakis simplex in Peter-the-Great gulf fishes that are a source of human
      invasion. Five of 19 fish types were found to be nematode-free, and the
      extensiveness and intensity of invasion were observed in Siberian salmons
      (Oncorhynchus keta) (61% and 2-700 worms, respectively), Alaska pollacks
      (Theragra chalcogramma) (75.7% and 1-31 worms), and brown rock trouts
      (Hexagrammos octogrammus) (100% and 1-60 worms). Autopsy showed that the
      distribution of larvae was ambiguous in different fish species. Data on the
      survival of Anisakis were also obtained under experimental conditions. The
      nematodes were ascertained to die at -8 degrees C at the moment of complete fish
      freezing. Anisakis may be alive in the unfrozen fish for more than 40 days. The
      death of worms in the salted fish occurs within 3-8 days only when 6-10/1000
      concentrations of NaCl salts are achieved at the sites of worms.

PMID- 15484975
TI  - [Evaluation of the occurrence of borreliae in the ticks].
AB  - The paper shows it necessary to estimate the average number of borreliae in the
      infected ticks, by using the geometric mean of a sign rather than the arithmetic
      mean.

PMID- 15484976
TI  - [Cardiac syndrome in opisthorchiasis].
AB  - According to the intensity and duration of invasion, superinvasion
      opisthorchiasis in laboratory animals and human beings involves all cardiac
      layers; the myocardium is mostly damaged. In its early phase, vascular
      inflammation of the microcirculatory bed, dystrophy, necrosis of striated muscle
      fibers progressing to diffuse cardiosclerosis result from abnormal immunological
      processes; due to reflex exposures (Botkin's syndrome), there may be persistent
      cardialgias that may progress to the clinical manifestations of chronic ischemic
      heart disease. Unpredictable dissipative clusters of metabolic Opistorchis may
      predispose to different forms of myocarditis progressing to focal and diffuse
      cardiosclerosis. In these cases, the death of patients with superinvasion
      opisthorchiasis results from acute or chronic heart failure. Dehelmintization in
      these patients fails to eliminate myocardial changes (cardiosclerosis) that
      further determine the clinical presentation of cardiac pathology.

PMID- 15484977
TI  - [Duodenogastroesophageal reflux disease as a complication of superinvasion
      opisthorchiasis].
AB  - In patients with superinvasion opisthorchiasis of prolonged invasion, 84% develop
      duodenal hypertension, 94% of the patients are found to have gastric
      hypertension; duodenogastric reflux with formation of chronic gastritis and
      reorganization is revealed in 75%. Reflux of gastric contents into the esophagus
      gives rise to chronic eosophagitis, regurgitation of intestinal contents into the
      pancreatic duct is a cause of chronic indurative pancreatitis of the head of the
      gland. In cases of duodenal hypertension, the rates of pancreatic O. felineus
      invasion are as high as 93.7%.

PMID- 15484978
TI  - [Colonic involvement in chronic opisthorchiasis].
AB  - OBJECTIVE: To provide clinical, functional, and morphological characteristics of
      colonic involvement in chronic opisthorchiasis and to evaluate the efficiency of
      dehelmintization. SUBJECTS AND METHODS: 96 patients with chronic non-ulcerative
      colitis, including 56 patients who had chronic opisthorchiasis (Group 1) and 40
      patients who had no parasitic diseases (Group 2). The biocenosis of the large
      bowel, the motor function and morphological status of its distal and proximal
      parts were evaluated in all the patients. Biopsy specimens were histologically
      studied. RESULTS AND DISCUSSION: There was an association of impaired colonic
      motor activity and morphological colonic mucosal changes with the intensity and
      duration of Opisthorchis invasion. A marked eosinophilic infiltration of the
      colonic mucosa was noted in all morphological types of chronic non-ulcerative
      colitis in patients with chronic opisthorchiasis. Effective dehelmintization
      caused positive functional and morphological changes in the large bowel. All the
      above facts support the likelihood of parasitic colitis in chronic
      opisthorchiasis and the expediency of dehelmintization.

PMID- 15484979
TI  - [Tropic malaria in a patient with HIV infection].

PMID- 15484980
TI  - [Investigation of the trichinellocidal activity of the agents from a series of
      benzthiazole and benzoxazole].

PMID- 15484981
TI  - [Population dynamics of Ixodes persulcatus in a subzone of the south taiga of the
      Middle Urals].
AB  - The results of a 27-year follow-up of the size of the taiga tick in a subarea of
      the south taiga of the Middle Urals are summarized. The author has established
      the period of its activity, the change in the parameter of the activity by years,
      and the rise in the size of the vector in the past decade.

PMID- 15484982
TI  - [Seroepidemiology of toxoplasmosis in pregnant women and neonatal infants].
AB  - A serological screening among pregnant females for toxoplasmosis in the Belgorod
      Region has shown a rise in the incidence of this infection in them during seven
      years (1996-2002). There is also a more than 2-fold increase in the rate of
      Toxoplasma infection by the second trimester. This increases a risk for fetal
      congenital malformations and the severity of neonatal congenital malformations.
      Different awareness levels are shown in fertile-age females from different
      administrative areas of the region.

PMID- 15484983
TI  - [A combination of natural foci of zoonoses (Review)].

PMID- 15484984
TI  - [Helminthoses in the Ivano-Frankovsk region].

PMID- 15484985
TI  - [Prevalence of the geohelminthoses in the Rovno region].

PMID- 15484986
TI  - [Human fascioliasis: status of the problem].

PMID- 15484987
TI  - [Present-day governmental policy in prevention of parasitic diseases in the
      population of Russia].

PMID- 15484988
TI  - More than "just a nurse".

PMID- 15484989
TI  - Will emergency contraception increase sexually transmitted infections?

PMID- 15484991
TI  - Influencing adolescent behaviors: a need for comprehensive sex education.

PMID- 15484992
TI  - A librarians' perspective on nursing practices. Baby organizing.

PMID- 15484993
TI  - Becoming a midwife teacher.

PMID- 15484995
TI  - Human trafficking. A health care perspective.

PMID- 15484996
TI  - Combating obesity. The health care providers' role.

PMID- 15484997
TI  - Evaluation and management. Female urinary incontinence.

PMID- 15484998
TI  - Do you ever leak urine? Tips for staying dry & healthy!

PMID- 15484999
TI  - Providing comprehensive services in a hospital outpatient center. After the
      birth.

PMID- 15485000
TI  - Do men have a role in maternal-newborn nursing? The male student nurse
      experience.

PMID- 15485001
TI  - The Dionne quintuplets. Perinatal care a la 1930s style.

PMID- 15485002
TI  - Silent lullabies. Helping parents cope with early pregnancy loss.

PMID- 15485003
TI  - Women encouraged to nurse their infants for six months or more. Promoting
      breastfeeding.

PMID- 15485004
TI  - Uterusectomy and my sexual response. Gauging its impact on holistic health.

PMID- 15485005
TI  - Cyclophosphamide in systemic sclerosis: light and shadows.

PMID- 15485006
TI  - Calcaneal quantitative ultrasound as a reliable tool in assessing osteoporosis
      and its risk factors in a large cohort of the Italian population.

PMID- 15485007
TI  - The Fibromyalgia Impact Questionnaire: a validated Spanish version to assess the
      health status in women with fibromyalgia.
AB  - OBJECTIVE: To translate, adapt, validate and assess the sensitivity to change of
      a Spanish version of the Fibromyalgia Impact Questionnaire (FIQ-S). METHODS: The
      FIQ-S was adapted following the translation and back-translation methodology.
      Female patients with fibromyalgia (FM) were invited to participate. Reliability
      was analyzed by the Spearman correlation coefficient between test and retest.
      Internal consistency was checked by the Cronbach's alpha coefficient. Construct
      validity was analyzed comparing FIQ-S with: HAQ, FHAQ, SF-36, SCL90-R, and the
      visual analogue scale for pain. Sensitivity to change was assessed in an 8-week
      randomized trial of exercise therapy. Feasibility was analyzed by the time taken
      in completing the FIQ-S and the proportion of patients able to complete the
      questionnaire. RESULTS: Translation was concordant. Adaptation affected at 4 sub
      items of physical function. One-hundred and two FM patients completed the
      protocol. Mean age was 48.7 years with a mean of 9.2 years of evolution. Test
      retest correlations were between 0.61-0.85 (p < 0.0001). Internal consistency
      showed alpha = 0.82 for all items and alpha = 0.86 for the sub-items of physical
      function. Significant correlations (p < 0.0001) were found between the FIQ-S
      items and HAQ, FHAQ, SF-36 and SCL90-R. For patients treated with the exercise
      program, the pre-treatment FIQ-S score was 52.0 +/- 11.5 and the post-treatment
      score was 40.8 +/- 13.7 (p < 0.003). Mean time for completing FIQ-S was 3.3
      minutes. In 4% of the patients external help was needed. CONCLUSION: The FIQ-S is
      a reliable, valid and responsive to changes questionnaire for measuring health
      status and physical function in Spanish speaking FM patients.

PMID- 15485008
TI  - Magnetic resonance imaging and proton magnetic resonance spectroscopy in neuro
      Behcet's disease.
AB  - OBJECTIVE: Neuro-Behcet's disease (NBD) is one of the most serious complications
      of Behcet's disease (BD). Proton magnetic resonance spectroscopy (1H MRS) has
      been proved to be useful in detecting neuro-metabolic abnormalities in various
      diseases affecting the brain. In this study, we attempted to characterize the
      magnetic resonance imaging (MRI) findings in Korean patients with NBD and then
      examined the usefulness of 1HMRS in evaluating the MRI-negative brain area of NBD
      patients. METHODS: We performed brain MRI in 18 BD patients with neurologic
      symptoms and signs. Seven NBD patients without thalamic lesions and 8 healthy
      controls underwent brain 1H MRS, in which an 8 ml voxel was placed in the left
      thalamus and the N-acetylaspartate (NAA)/creatine (Cr) ratio was measured.
      RESULTS: Fourteen of 18 BD patients were diagnosed as having NBD and 12 NBD
      patients (86%) had brain lesions on MRI. Most lesions were of high signal
      intensity on T2-weighted images and located in the midbrain, pons, basal ganglia,
      and white matter. On 1H MRS, the thalamic area without gross abnormalities on MRI
      showed a significantly lower NAA/Cr ratio in NBD patients compared to healthy
      controls (1.07 +/- 0.08 versus 1.54 +/- 0.27, P < 0.01). In 2 NBD patients, the
      NAA/Cr ratios, monitored serially, were normalized along with clinical
      improvement 6 months after treatment with prednisolone and immune suppressive
      agents. CONCLUSION: MRI is a very sensitive diagnostic method for NBD, and 1H MRS
      may be useful for the early detection and follow-up of MRI-negative NBD.

PMID- 15485009
TI  - Efficacy and safety of a musically modulated electromagnetic field (TAMMEF) in
      patients affected by knee osteoarthritis.
AB  - OBJECTIVE: Numerous studies have demonstrated the utility of extremely low
      frequencies (ELF) electromagnetic fields in clinical practice. Moreover, the
      effects of these fields seems to depend on their respective codes (frequency,
      intensity, waveform). In our study we want to value the effects of the TAMMEF
      (Therapeutic Application of a Musically Modulated Electromagnetic Field) system,
      which field is piloted by a musical signal. METHODS: Ninety subjects, affected by
      primary osteoarthritis of the knee, were enrolled in the study and randomly
      divided into three groups of 30 patients each: A exposed to TAMMEF, B exposed to
      ELF, C exposed to a simulated field. All subjects underwent a cycle of 15 daily
      sessions of 30 minutes each and a clinical examination upon enrolment, after 7
      days of therapy, at the end of the cycle and at a follow-up 30 days later:
      RESULTS: All the patients of groups A and B completed the therapy without the
      appearance of side effects: they presented a significant improvement of the
      subjective pain and the functional limitation, which remained stable at the
      follow-up examination. In group C, there was no improvement of the pain symptoms
      or articular functionality. CONCLUSIONS: This study suggests that the TAMMEF
      system is efficacious in the control of pain symptoms and in the reduction of
      functional limitation in patients with knee osteoarthritis. Moreover, the effects
      of the TAMMEF system cover those produced by the ELF field.

PMID- 15485010
TI  - Intravenous cyclophosphamide therapy for systemic sclerosis. A single-center
      experience and review of the literature with pooled analysis of lung function
      test results.
AB  - OBJECTIVE: Oral cyclophosphamide (CYC) is a promising therapy for Systemic
      Sclerosis (SSc)-related interstitial lung disease (ILD). The use of intravenous
      (i.v.) pulses has been considered as an alternative route of drug administration,
      possibly associated with reduced toxicity. Our objectives were to re-evaluate our
      experience with i.v. CYC, to review the literature, and to pool our results with
      those available from other groups, improving the statistical power of the
      analysis. METHODS: 1) Retrospective analysis of our center experience on 16
      patients with SSc and active alveolitis, treated with i.v. CYC 750 mg + 6
      methylprednisolone 125 mg every 3 weeks. 2) Pooled analysis of papers published
      in peer-reviewed journals reporting detailed data on each patient treated with
      i.v. CYC. The end-point was modification in the results of lung function tests
      (LFT) after 6 months. Piecewise regression analysis was performed using a linear
      mixed-effects model adjusted for baseline values to evaluate the changes in LFT.
      RESULTS: Retrospective analysis. In the period before therapy there was a
      significant deterioration in FVC (in 6 months: -4.3%; p=0.0009) and DLCO (-2.1%;
      p=0.018). After 6 months of treatment there was a modest improvement in the FVC
      (+2.7% p=0.08) and DLCO (+2.2%; p=0.08). Pooled analysis. In 53 evaluable
      patients, the improvement in LFT reached conventional statistical significance
      (FVC: +2.85%; 95% confidence intervals: +0.04, +5.66%; p=0.04. DLCO: +4.4%; 95%
      confidence intervals: +1.2%, +7.5%; p<0.001). CONCLUSION: i.v. CYC for 6 months
      can achieve a small, but significant improvement of LFT in patients with SSc and
      active alveolitis.

PMID- 15485011
TI  - Clinical optimization and multicenter validation of antigen-specific cut-off
      values on the INNO-LIA ANA update for the detection of autoantibodies in
      connective tissue disorders.
AB  - OBJECTIVES: The INNO-LIA ANA Update is a qualitative multiparameter line
      immunoassay for detection of autoantibodies to several different antigens
      associated with connective tissue disorders. We sought to optimize and validate
      the cut-off values for its antigen-specific components: SmB, SmD, RNP-70k, RNP-A,
      RNP-C, SSA/Ro52, SSA/Ro60, SSB/La, Cenp-B, Topo-I, Jo-1, ribosomal P, and
      histones. Our aim was to achieve 98% specificity for each of the markers, with
      respect to differential disease controls, while maintaining sensitivity. METHODS:
      For optimization, the cut-off value of the different antigen lines was fixed to
      achieve this specificity using an in-house set of 955 patient samples.
      Specificity was validated at multiple sites using a different set of 330 samples
      obtained from 158 apparently healthy blood donors, 100 patients with a variety of
      infections, 20 each with Wegener's granulomatosis, inflammatory bowel disease,
      and primary antiphospholipid syndrome, and 12 with psoriatic arthritis.
      Sensitivity was evaluated, using this optimized cut-off control, in 147 patients
      with scleroderma, 93 with Sjogren's disease, 40 with systemic lupus
      erythematosus, 40 with rheumatoid arthritis, 39 with mixed connective tissue
      disease, and 19 with polymyositis. Sensitivity and specificity of the INNO-LIA
      ANA Update were determined using the clinical diagnosis as reference. RESULTS:
      The optimized cut-off values resulted in a specificity 98% or more for all LIA
      markers except one (histones 97.8%) in the validation set of 330 samples. The
      sensitivity for each marker tested in 378 samples from the target patient groups
      was comparable to that reported in the literature. CONCLUSION: The INNO-LIA ANA
      Update shows uniformly high specificities combined with sensitivities very
      similar to those of reference assays, in a single test format.

PMID- 15485012
TI  - Efficacy and tolerability of lumiracoxib versus placebo in patients with
      osteoarthritis of the hand.
AB  - OBJECTIVE: This multicentre, randomized, double-blind, placebo-controlled
      parallel-group study was undertaken to investigate the efficacy, safety and
      tolerability of lumiracoxib (Prexige), a cyclooxygenase-2 selective inhibitor, in
      patients with primary osteoarthritis (OA) of the hand. METHODS: The study
      randomized 594 patients aged > or = 18 years with symptomatic OA of the hand.
      Patients underwent a 3 to 7-day washout for previous nonsteroidal anti
      inflammatory drugs and those with pain intensity > or = 40 mm on a 100 mm Visual
      Analogue Scale (VAS) in the target hand during the 24 hours prior to baseline and
      an increase in pain intensity of either > or = 20% or > or = 10 mm VAS since
      screening (whichever was greater) were randomized to lumiracoxib 200 mg once
      daily (od) (n=205), lumiracoxib 400 mg od (n=193) or placebo (n=196). The primary
      efficacy variable was overall OA pain intensity (VAS mm) in the target hand after
      4 weeks of treatment. Safety and tolerability assessments were performed.
      RESULTS: After 4 weeks of treatment, overall OA pain intensity in the target hand
      was significantly lower for patients treated with lumiracoxib compared with
      patients treated with placebo (both doses p<0.001). There was no significant
      difference between lumiracoxib doses in terms of the reduction in overall OA pain
      intensity. Lumiracoxib was well tolerated. The incidence of adverse events was
      similar for active treatment groups and placebo. CONCLUSIONS: Lumiracoxib 200 and
      400 mg od were effective and well tolerated treatments for OA of the hand.
      Lumiracoxib significantly improved overall OA pain intensity in the target hand
      versus placebo, with a tolerability profile similar to placebo.

PMID- 15485013
TI  - Matrix metalloproteinase-8 in sera and from polymorphonuclear leucocytes in
      rheumatoid arthritis: in vitro characterization and correlation with disease
      activity.
AB  - OBJECTIVES: To determine matrix metalloproteinase-8 (MMP-8) secretion from
      rheumatoid arthritis (RA) peripheral blood polymorphonuclear leucocytes (PMNs),
      in response to immune complexes (IC), cytokines and their combinations, and to
      study correlation of serum MMP-8 with disease activity. METHODS: PMNs from RA
      patients and controls were stimulated in vitro with interleukin-15 (IL-15), IL
      18, adherent immune complexes, rabbit anti-human immunoglobulin G (anti-HIgG),
      human immunoglobulin G (HIgG), and their F (ab') 2 prongs, phorbol myristate
      acetate (PMA) or combinations of above. Supernatants from these experiments and
      sera from both groups were assayed for MMP-8 using ELISA and correlated with
      disease activity measures in patients. RESULTS: MMP-8 secretion from stimulated
      PMNs was compared to unstimulated PMNs. Immune complexes elicited significant MMP
      8 secretion (p = 0.006 and 0.001, control and RA respectively). Unlike HIgG and
      its F (ab')2 fragment, very high secretion was elicited by anti-HIgG (242.37 +/-
      10.85 ng/ml) and its F (ab')2 prong (195.85 +/- 28.67 ng/ml). IL-15 did not
      elicit any secretion. IL-18 with PMA increased secretion significantly only from
      RA PMNs (p = 0.003). Serum MMP-8 correlated positively with serum CRP (p = 0.017)
      and not with disease activity score (p = 0.199). CONCLUSIONS: We for the first
      time demonstrate that immune complexes elicit MMP-8 secretion from PMNs. Except
      for higher secretion from RA PMNs in response to combination of IL-18 and PMA,
      both control and RA PMNs respond similarly to various stimuli. Secretion by anti
      HIgG occurs by a mechanism independent of Fc receptor. Correlation with CRP
      suggest that serum MMP-8 may be an indicator of acute inflammatory activity.

PMID- 15485014
TI  - MMP-2/gelatinase A is a gene product of human adult articular chondrocytes and is
      increased in osteoarthritic cartilage.
AB  - OBJECTIVE: Collagen fibril degeneration involves initially the cleavage within
      the triple helix by the collagenases (1 and 3), but then mainly involves also the
      gelatinases, of which gelatinase A (MMP-2) appears to play a central role in many
      tissues. The objective of this study was to determine the quantitative expression
      levels as well as the distribution in normal and osteoarthritic cartilage of
      gelatinase A and in cultured articular chondrocytes with and without stimulation
      by Il-1beta. METHODS: Conventional and online PCR technology and
      immunohistochemistry were used to determine MMP-2 expression levels on the mRNA
      and protein level. RESULTS: Conventional PCR analysis could demonstrate the
      presence of MMP-2 mRNA in normal and osteoarthritic chondrocytes. Online
      quantitative PCR confirmed the presence of MMP-2 mRNA expression in normal
      articular chondrocytes in vivo (and in vitro). An increase of 5x (p < 0.001) was
      observed in osteoarthritic cartilage in vivo. Of note, no significant up
      regulation of gelatinase A was observed by Il-1beta in vitro. Immunostaining for
      gelatinase A confirmed the presence of MMP-2 with mono- and polyclonal antibodies
      in normal and osteoarthritic chondrocytes with somewhat higher levels observed in
      the latter. CONCLUSIONS: The presented results confirm the increased expression
      of gelatinase A by osteoarthritic articular chondrocytes as previously described.
      Of note, also normal adult articular chondrocytes expressed significant amounts
      of gelatinase A in vivo and in vitro suggesting gelatinase A as being also
      involved in physiological collagen turnover in human adult articular cartilage.

PMID- 15485015
TI  - Better results with rhenium-186 radiosynoviorthesis than with cortivazol in
      rheumatoid arthritis (RA): a two-year follow-up randomized controlled multicentre
      study.
AB  - OBJECTIVE: The aim of this international multicentric randomized phase 3 clinical
      trial was to compare prospectively radiosynoviorthesis (RSO) with rhenium-186
      sulfide (186Re) to intra-articular corticotherapy in patients with clinically
      controlled rheumatoid arthritis (RA), but in whom one or a few medium-sized
      joints remained painful or swollen. METHODS: One hundred and twenty-nine joints
      in 81 RA patients [stratified into 2 groups: wrists (group 1, n = 78) and all the
      other joints (group 2, n = 51, including 18 elbows, 21 shoulders and 12 ankles)]
      were randomized to receive intra-articular injections of either 186Re-sulfide (64
      +/- 4 MBq), or cortivazol (Altim) 3.75 mg. Clinical assessment was performed
      before and then at 3, 6, 12, 18 and 24 months after local therapy, using a 4-step
      verbal rating scale (VRS) and a 100 mm visual analog scale for pain, a 4-step VRS
      for joint swelling and mobility and a 2-step VRS for the radiological stage. The
      Mantel-Haenszel test was used for qualitative variables, analysis of variance
      (ANOVA) for quantitative pain analysis and Kaplan-Meyer survival test for relapse
      analysis. RESULTS: 186Re was observed to be statistically superior to cortivazol
      at 18 and 24 months while no statistical difference was seen for any criterion at
      3, 6 and 12 months post injection. At 24 months, the difference in favor of 186Re
      was significant for pain (p = 0.024), joint swelling (p = 0.01), mobility (p =
      0.05, non-wrists only), pain and swelling (p = 0.03) and pain or swelling (p =
      0.02). "Survival" studies (Kaplan-Meyer) demonstrated a greater relative risk of
      relapse in corticoid treated joints, but only from the second year of follow-up.
      No serious side effect was observed in any patient, with only light and transient
      local pain and/or swelling occurring in 24% of cases, regardless of the treatment
      used. CONCLUSION: 186Re-sulfide and cortivazol had similar efficacy up to 12
      months post-injection, but 186Re became clearly more effective at 18 and 24
      months, for all criteria monitored and for RA outcome. Therefore, 186Re RSO can
      be recommended for routine clinical use.

PMID- 15485016
TI  - Increased dermal elastic fibers in the tight skin mouse.
AB  - OBJECTIVE: The tight skin (Tsk-1) mouse has been proposed as a model for systemic
      sclerosis on the basis of increased accumulation of collagen and
      glycosaminoglycans in the skin, and by the presence of serum autoantibodies. The
      genetic basis of the mutation has been identified as a genomic duplication within
      the fibrillin-1 (Fbn-1) gene that results in a larger than normal Fbn-1
      transcript, but the mechanism that leads to dermal fibrosis is unclear Fibrillin
      molecules associate into a polymer that is coated with elastin molecules to form
      elastic fibers. To further evaluate the Tsk-1 mouse model of scleroderma, we have
      studied elastic fibers in the skin of these mice. METHODS: Skin sections obtained
      from C57BL/6-TSK+ (Tsk-1) and C57BL6-pa/+ (control) mice were stained with
      Masson's trichrome for evaluation of collagen and Gomori's aldehyde fuchsin stain
      for elastic tissue. Computer assisted image analysis was performed to quantify
      differences in histologic sections. RESULTS: Tsk-1 mice had a highly significant
      increase in the percentage of elastic fibers (19.6%) in the dermis compared to
      control mice (7.9%) [p < 0.001]. This correlates with the findings in the skin of
      systemic sclerosis patients where increased elastic fibers have been observed. In
      addition, an increased level of dermal collagen staining was also observed in the
      Tsk-1 dermis (82.9%) compared with the level in normal sections (73.7%) [p <
      0.01]. CONCLUSION: These data support the use of the Tsk-1 mouse as a model for
      the connective tissue abnormalities of human scleroderma.

PMID- 15485017
TI  - Wrist joint involvement in systemic lupus erythematosus. An ultrasonographic
      study.
AB  - OBJECTIVE: To define joint alterations in the wrists of patients with systemic
      lupus erythematosus (SLE) by ultrasonography (US). METHODS: Fifty-two wrists of
      26 SLE patients and 30 wrists of 15 healthy controls were evaluated using US by
      two different experienced operators, blinded to the clinical data. A 14 MHz
      linear probe was used. Power Doppler (PD) was applied to evaluate the presence of
      synovial neoangiogenesis as a parameter of active local synovitis. The findings
      were correlated to the clinical evaluation, serological systemic disease activity
      parameters (ESR, C3 levels) and the SLE-disease activity score (SLEDAI).
      Statistical analysis was performed by the EPISTAT program. RESULTS: Signs of
      synovitis were found in 22 wrists (42.3%). Synovial proliferation was present in
      10 joints (19.2%), PD positivity in 5 (9.6%) and joint effusion in 13 (25%).
      Erosions were present in both wrists (3.8%) of one patient. Signs of
      tenosynovitis of one or more tendons were shown in 23 cases (44.2%). Ganglia were
      found in 2 joints (3.8%). Changes of the median nerve, joint dislocations,
      tendons' ruptures, cysts and nodules were never detected. In 14 wrists (26.9%) no
      alterations were found. There was no correlation between sonographic findings and
      clinical, laboratory and indexes signs of disease activity. In the control group
      the only alteration found was tenosynovitis in 1 joint (p < 0.0001). CONCLUSION:
      US proved to be an useful technique to detect wrist joint alterations in SLE.
      These findings may help the physician to modulate treatment strategies and to
      perform a low cost monitoring of joint disease activity.

PMID- 15485018
TI  - Systemic sclerosis developing in association with the use of interferon alpha
      therapy for chronic viral hepatitis.
AB  - In 1992 interferon alpha (IFNalpha) was approved by the FDA for the treatment of
      chronic viral hepatitis B and C. Since then IFNalpha has been implicated in the
      development of several autoantibodies as well as in the development or
      exacerbation of various autoimmune disorders. Herein, we describe a 47-year-old
      female who developed a limited form of systemic sclerosis (SSc) with lung
      involvement 6 months after the institution of IFNalpha therapy for chronic active
      hepatitis C. There was no family or personal history of autoimmune diseases. We
      speculate that the immunomodulatory effects of IFNalpha triggered the clinical
      manifestations of SSc in this patient. To our knowledge, this is the second case
      of SSc developing after therapy with IFNalpha and the first in a patient treated
      for chronic viral hepatitis C.

PMID- 15485019
TI  - Successful treatment of relapsing polychondritis with infliximab.
AB  - Relapsing polychondritis (RP) is a rare and potentially fatal autoimmune disease
      in which an inappropriate immune response destroys the cartilage of the ears,
      larynx and nose. Many therapeutic approaches have been reported. We describe the
      results obtained with infliximab in a patient with RP unresponsive to
      conventional therapy. This therapy could be a new weapon to treat refractory RP.

PMID- 15485020
TI  - Cutaneous manifestations of primary Sjogren's syndrome are underestimated.
AB  - The association of kerato-conjunctivitis sicca and xerostomia has been termed
      Sjogren's syndrome (SS). Although this disease is referred to as a non-organ
      specific autoimmune condition, the vast majority of the deleterious effects of
      primary SS are restricted to the exocrine glands. Among them, the lacrymal and
      salivary glands are at the foreground, owing to the severity of the objective
      consequences and the importance of the subjective manifestations. As a result,
      cutaneous manifestations are minimized, albeit relatively common. We have
      carefully analyzed the literature to draw up an inventory of the possible skin
      complications of this syndrome. In addition to xerosis and epidermal IgG
      deposits, they include vasculitis and cutaneous B cell lymphoma. Alopecia,
      vitiligo and papular lesions have also been reported to be associated with
      primary SS.

PMID- 15485021
TI  - Unilateral destructive wrist synovitis in juvenile idiopathic arthritis.
AB  - OBJECTIVE: To describe the clinical and radiographic features of a group of
      juvenile idiopathic arthritis (JIA) patients who developed unilateral destructive
      wrist synovitis. METHODS: All wrist radiographs performed yearly between 1986 and
      2002 in JIA patients who had wrist involvement were retrospectively reviewed to
      identify patients who had unilateral erosive wrist synovitis, defined as a
      difference of at least -3 units in the Poznanski score between the affected wrist
      and the unaffected wrist, with the Poznanski score in the unaffected wrist being
      > -2 units throughout the follow-up period. Clinical and radiographic data
      obtained during follow-up were recorded for all patients. RESULTS: Of a total of
      250 patients for whom we had approximately 900 wrist radiographs, 6 patients were
      found to have unilateral erosive wrist synovitis. The JIA onset subtype was
      oligoarticular in 5 patients and polyarticular in 1 patient and the disease
      duration from presentation to the last follow-up visit ranged from 2 to 16 years.
      The arthritis course was polyarticular in all patients. Five patients had
      positive antinuclear antibodies (ANA) and 1 had positive rheumatoid factor (RF).
      At the last follow-up visit, all patients had some impairment of wrist function
      and 2 patients had wrist subluxation. There was a marked radiographic damage in
      all affected wrist, with the Poznanski ranging from -8.0 to -8.50 units in 3
      patients and being -5.5, -3.1 and -2.4 units, respectively, in 3 patients. The
      severity of radiographic damage in the ANA-positive patients with the longest
      disease duration was comparable to that observed in the RF-positive patient.
      CONCLUSION: Unilateral erosive wrist synovitis seems to be uncommon in JIA.
      Patients with unilateral wrist synovitis may be at risk of a destructive course
      irrespective of the JIA onset subtype.

PMID- 15485022
TI  - Intra-articular steroids in radiologically confirmed tarsal and hip synovitis of
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: To estimate the value of MRI or US imaging in the diagnosis of
      synovitis and the response to local steroid therapy in tarsal and hip synovitis.
      METHODS: 32 patients with juvenile idiopathic arthritis (JIA), 19 of them with 22
      tarsal and 13 of them with 20 hip synovitis, were followed up for 12 months after
      intra-articular corticosteroid treatment (IAST). MRI was taken from swollen
      ankles/feet to target the inflamed area before IAST. The synovitis in hip joints
      was assessed by both clinical and ultrasonographic examination. RESULTS: MRI
      showed that in the swollen tarsal area the inflammation was distributed widely in
      the joints and tendon sheaths. In 13/22 (59%) ankles/feet, synovitis was observed
      in multiple joint spaces. In 17/22 (77%) ankles/feet, tenosynovitis was present.
      In 32% of cases, the IAST induced clinical remission for up to 12 months. In hip
      synovitis, ultrasound supplemented clinical assessment. At 12 months after IAST a
      successful treatment response was seen in 10/20 (50%) hips. CONCLUSION: In
      unresponsive tarsal arthritis, the synovitic sites should be targeted by
      radiological imaging to improve the efficacy of corticosteroid injections. For
      pediatric rheumatologists, easy access to US is preferable to optimize the
      treatment of hip and tarsal synovitis in JIA.

PMID- 15485023
TI  - Lymphoproliferative disorders in paediatric rheumatic diseases. A report of two
      cases.
AB  - Lymphoproliferative disorders (LPD) are reported with a much lower frequency in
      children with rheumatic diseases than in their adult counterparts. We describe 2
      patients who developed a lymphoma during the course of the disease. The first is
      a 16-year-old girl diagnosed with systemic juvenile idiopathic arthritis 6 years
      before who developed a mucosa-associated lymphoid tissue (MALT) lymphoma. The
      second report involves a boy diagnosed with systemic lupus erythematosus at 9
      years of age who developed a Hodgkin's lymphoma 9 years after the disease onset.
      In spite of the low frequency of LPD in children with rheumatic diseases, these
      processes do occur.

PMID- 15485024
TI  - Benzbromarone withdrawn from the European market: another case of "absence of
      evidence is evidence of absence"?

PMID- 15485025
TI  - Polymyositis associated with HIV infection during immune restoration induced by
      highly active anti-retroviral therapy.

PMID- 15485026
TI  - Multiple sclerosis and the antiphospholipid (Hughes) syndrome: a common
      differential diagnosis?

PMID- 15485027
TI  - Sensorineural hearing impairment in systemic lupus erythematosus: sudden or
      progressive?

PMID- 15485028
TI  - Are you asking the right questions.

PMID- 15485029
TI  - Speakers tackle controversy surrounding swine welfare assessments.

PMID- 15485030
TI  - Emerging animal welfare ethic transcends borders.

PMID- 15485031
TI  - Sentient property: a novel animal law proposal.

PMID- 15485032
TI  - Controversy, confusion continue to surround vaccine guidelines.

PMID- 15485033
TI  - Pursue your passion for the ecosystem.

PMID- 15485034
TI  - Runoff contributes to emergence of disease in marine mammals.

PMID- 15485035
TI  - Changes on the horizon for National Veterinary Accreditation Program.

PMID- 15485036
TI  - Controlling health care costs.

PMID- 15485037
TI  - A disabling injury or long-term illness.

PMID- 15485038
TI  - Thoughts on veterinarian-client communications.

PMID- 15485039
TI  - Concurs with findings on heart murmurs in cats.

PMID- 15485040
TI  - What is your diagnosis? Urethral trauma.

PMID- 15485041
TI  - ECG of the month. Complete AV block, and lack of capture (pacing) of the
      ventricles by the single-lead atrial-sensing VDD system.

PMID- 15485042
TI  - Theriogenology question of the month. How would you confirm a diagnosis of
      mycotic infection in an aborted fetus?

PMID- 15485043
TI  - Search-and-rescue dogs: an overview for veterinarians.

PMID- 15485044
TI  - Medical and behavioral surveillance of dogs deployed to the World Trade Center
      and the Pentagon from October 2001 to June 2002.
AB  - OBJECTIVE: To evaluate early medical and behavioral effects of deployment to the
      World Trade Center, Fresh Kills Landfill, or the Pentagon on responding search
      and-rescue (SAR) dogs. DESIGN: Prospective double cohort study. ANIMALS: The
      first cohort included SAR dogs responding to the September 11, 2001, terrorist
      attacks (deployed), and the second cohort included SAR dogs trained in a similar
      manner but not deployed (controls). Enrollment occurred from October 2001 to June
      2002. PROCEDURE: Dogs were examined by their local veterinarians; thoracic
      radiographs and blood samples were shipped to the University of Pennsylvania for
      analysis. Handlers completed medical and training histories and a canine
      behavioral survey. RESULTS: Deployed dogs were older and had more search
      experience than control dogs. Serum concentrations of globulin and bilirubin and
      activity of alkaline phosphatase were significantly higher in deployed dogs,
      independent of age and training. Despite significant differences in several blood
      parameters, values for both groups were within reference ranges. No pulmonary
      abnormalities were detected on radiographs, and no significant differences in
      behavior or medical history were detected between groups. CONCLUSIONS AND
      CLINICAL RELEVANCE: Within the first year following the September 11 attacks,
      there was no evidence that responding dogs developed adverse effects related to
      their work. Mild but significantly higher serum concentrations of globulin and
      bilirubin and activity of alkaline phosphatase in deployed dogs suggested higher
      antigen or toxin exposure. These dogs will be monitored for delayed effects for
      at least 3 years.

PMID- 15485045
TI  - Deployment morbidity among search-and-rescue dogs used after the September 11,
      2001, terrorist attacks.
AB  - OBJECTIVES: To determine characteristics, variables associated with deployment
      morbidity, and injuries and illnesses of search-and-rescue dogs associated with
      the Sept 11, 2001, terrorist attacks. DESIGN: Historical cohort study. ANIMALS:
      96 dogs. PROCEDURE: Data collected included previous medical or surgical history,
      physical attributes of dogs, type and number of years of training, site of
      deployment, shift and hours worked, and number of days deployed. Combined
      morbidity was defined as 1 or more abnormalities of body systems, including
      traumatic injuries. RESULTS: Handlers of 96 of the 212 dogs responded to the
      surveys. Fifty-nine dogs were deployed by the Federal Emergency Management
      Agency, 10 by police forces, and 27 as members of other search-and-rescue teams.
      Sixty-five dogs (incidence rate, 17 events/1,000 dog search hours) had combined
      morbidity during deployment. System-specific morbidity rates included
      gastrointestinal tract signs (5 events/1,000 dog search hours), cuts and
      abrasions mostly on the feet (5 events/1,000 dog search hours), fatigue (6
      events/1,000 dog search hours), change in appetite (6 events/1,000 dogs search
      hours), dehydration (5 events/1,000 dog search hours), respiratory tract problems
      (2 events/1,000 dog search hours), heat exhaustion (2 events/1,000 dog search
      hours), and orthopedic or back problems (2 events/1,000 dog search hours). Dogs
      deployed to the World Trade Center were 6.6 times more likely to have combined
      morbidity, compared with dogs at the Pentagon. CONCLUSIONS AND CLINICAL
      RELEVANCE: Injury and illnesses occurred in most dogs and affected several organ
      systems, but all were minor.

PMID- 15485046
TI  - Employment and age of male and female AVMA members, 2003.

PMID- 15485047
TI  - Determination of the dosage of clomipramine for the treatment of urine spraying
      in cats.
AB  - OBJECTIVE: To determine the optimal dosage of clomipramine for the treatment of
      urine spraying in cats. DESIGN: Randomized controlled multicenter clinical trial.
      ANIMALS: 67 neutered cats. PROCEDURE: Cats with a minimum 1-month history of
      spraying urine against vertical surfaces at least twice per week were randomly
      assigned to be treated with a placebo or with clomipramine at a dosage of 0.125
      to 0.25 mg/kg (0.057 to 0.11 mg/lb), 0.25 to 0.5 mg/kg (0.11 to 0.23 mg/lb), or
      0.5 to 1 mg/kg (0.23 to 0.45 mg/lb), p.o., every 24 hours for up to 12 weeks.
      Owners of all cats were given information on behavioral treatment and
      environmental modification. RESULTS: Prior to treatment, mean number of urine
      spraying events ranged from 0.9 to 1.3 urine spraying events/d for the 4 groups,
      and mean percentage of days with urine spraying events ranged from 62% to 69%.
      All 3 dosages of clomipramine were associated with significant reductions in
      frequency of urine spraying. Sedation was the most common adverse effect and was
      identified in 27 of the 50 cats treated with clomipramine; however, treatment was
      not discontinued in any cat because of sedation. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results of the present study suggest that compared with a placebo,
      clomipramine significantly reduces the frequency of urine spraying in cats in
      terms of the number of urine spraying events per day and the number of days with
      urine spraying events. For cats with urine spraying, the recommended initial
      dosage of clomipramine is 0.25 to 0.5 mg/kg, p.o., every 24 hours.

PMID- 15485048
TI  - Outcome of cats with diarrhea and Tritrichomonas foetus infection.
AB  - OBJECTIVE: To determine the long-term outcome of cats infected with
      Tritrichomonas foetus and identify treatment and management strategies
      influencing resolution of infection or associated diarrhea. DESIGN: Prospective
      study. SAMPLE POPULATION: 26 cats with T. foetus-associated diarrhea at least 22
      months prior to the study. PROCEDURE: A standardized survey regarding clinical
      course and management was administered to owners of cats with T. foetus infection
      and associated diarrhea. Fecal samples were obtained from each cat; the presence
      of T. foetus was assessed via microscopic examination of smears, culture in
      commercial media, and polymerase chain reaction amplification of T. foetus rDNA
      involving species-specific primers. RESULTS: Survey responses were obtained from
      owners of all 26 cats. Twenty-three cats had complete resolution of diarrhea a
      median of 9 months after onset. Analysis of fecal samples obtained from 22 cats
      revealed persistent T. foetus infection in 12, with a median of 39 months after
      resolution of diarrhea. History of implementation of a dietary change, treatment
      with paromomycin, or higher numbers of cats in the household was associated with
      significantly longer duration of time to resolution of diarrhea. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested chronic T. foetus-associated diarrhea in
      most cats is likely to resolve spontaneously within 2 years of onset. Chronic
      infection with T. foetus (without clinical signs) after resolution of diarrhea
      appears to be common. Although often temporarily effective in decreasing severity
      of diarrhea, attempts to treat cats with T. foetus infection may result in
      prolongation of time to resolution of diarrhea.

PMID- 15485050
TI  - Underlying cause, pathophysiologic abnormalities, and response to treatment in
      cats with septic peritonitis: 51 cases (1990-2001).
AB  - OBJECTIVE: To determine the underlying cause, pathophysiologic abnormalities, and
      response to treatment in cats with septic peritonitis and identify differences
      between cats that survived following treatment and cats that did not survive
      despite treatment. DESIGN: Retrospective study. ANIMALS: 51 cats with septic
      peritonitis. PROCEDURE: Medical records were reviewed for clinical findings;
      results of clinicopathologic testing, microbial culture, and radiography;
      diagnosis; treatment; and outcome. RESULTS: Signs of pain during palpation of the
      abdomen were reported for only 29 of 47 (62%) cats. Eight (16%) cats had relative
      bradycardia (heart rate < 140 beats/min). The most commonly isolated organisms
      included Escherichia coli, Enterococcus spp, and Clostridium spp. The most common
      cause of peritonitis was gastrointestinal tract leakage (24 cats). No definitive
      source could be identified in 7 cats. Treatment, including exploratory surgery,
      was pursued in 23 cats, of which 16 (70%) survived and were discharged. There
      were no significant differences between survivors and nonsurvivors in regard to
      heart rate, age, rectal temperature, serum lactate concentration, WBC count, PCV,
      blood glucose concentration, or serum albumin concentration. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggest that clinicopathologic abnormalities and
      outcome in cats with septic peritonitis are similar to those reported for dogs.
      However, certain features may be unique, including an absence of signs of pain
      during abdominal palpation, relative bradycardia, and apparent spontaneous
      peritonitis in some cats.

PMID- 15485049
TI  - Molecular and serologic evidence of Anaplasma phagocytophilum infection in cats
      in North America.
AB  - Anaplasma phagocytophilum DNA was detected in blood of clinically ill cats from
      Massachusetts (n = 4) and Connecticut (1) by use of polymerase chain reaction
      assay and DNA sequencing. All 5 cats were allowed outdoors, and Ixodes scapularis
      were found on 3 cats. Clinical signs of fever, anorexia, and lethargy resolved
      quickly after treatment with doxycycline or tetracycline. Serum samples from each
      cat reacted with A. phagocytophilum morulae via an indirect fluorescent antibody
      assay; positive antibody titers persisted even after 21 to 30 days of treatment
      with tetracycline. To the authors' knowledge, this is the first report of A.
      phagocytophilum infection of domestic cats in North America. Results suggest that
      infection with the organism may be associated with clinical illness in some cats.

PMID- 15485051
TI  - Prevalence of anthelmintic resistant cyathostomes on horse farms.
AB  - OBJECTIVE: To determine prevalence of anthelmintic resistance in cyathostome
      nematodes of horses in the southern United States. DESIGN: Cross-sectional study.
      ANIMALS: 786 horses on 44 farms and stables in Georgia, South Carolina, Florida,
      Kentucky, and Louisiana. PROCEDURE: Fecal egg count (FEC) reduction tests were
      performed on 44 large farms and stables. Horses on each farm were treated with an
      oral paste formulation of fenbendazole, oxibendazole, pyrantel pamoate, or
      ivermectin at recommended label dosages. A mixed linear model was fitted to the
      percentage reduction in FEC, accounting for differences among farms, states,
      ages, treatments, and treatment by state interactions. RESULTS: By use of a
      conservative measure of resistance (< 80% reduction), the percentage of farms
      with anthelmintic-resistant cyathostomes was 97.7%, 0%, 53.5%, and 40.5% for
      fenbendazole, ivermectin, oxibendazole, and pyrantel pamoate, respectively. Mean
      percentage reductions in FEC for all farms were 24.8%, 99.9%, 73.8%, and 78.6%
      for fenbendazole, ivermectin, oxibendazole, and pyrantel pamoate, respectively.
      Pairwise contrasts between states for each treatment revealed that in almost all
      instances, there were no significant differences in results between states.
      CONCLUSIONS AND CLINICAL RELEVANCE: The prevalence of resistance found in this
      study was higher than that reported previously, suggesting that anthelmintic
      resistance in equine cyathostomes is becoming a major problem. Furthermore, data
      from these 5 southern states, which are geographically and physiographically
      distinct, were remarkably similar. This suggests that drug resistance in
      cyathostomes is highly prevalent throughout the entire southern United States and
      probably nationwide.

PMID- 15485052
TI  - Use of a hand-assisted laparoscopic technique for removal of a uterine leiomyoma
      in a standing mare.
AB  - A 20-year-old Thoroughbred mare was evaluated because of a 2-year history of
      infertility. The mare had normal estrous cycles and had been bred 7 times by
      different stallions. Ultrasonographic examination revealed a homogeneous
      hyperechoic intramural mass in the tip of the right uterine horn; the mass was
      also detected via hysteroscopy Unilateral ovariectomy and partial hysterectomy
      were performed by use of a hand-assisted laparoscopic technique. Leiomyoma was
      diagnosed via histologic examination of the mass. Unilateral ovariectomy and
      partial hysterectomy are recommended in mares with leiomyoma in a uterine horn,
      especially if the tumor is associated with infertility. The hand-assisted
      laparoscopic technique allows direct visualization of abdominal structures and
      accurate placement of ligatures without applying tension on the broad ligament,
      and eliminates the risks and costs of general anesthesia.

PMID- 15485053
TI  - Evaluation of rumen transfaunation after surgical correction of left-sided
      displacement of the abomasum in cows.
AB  - OBJECTIVE: To evaluate rumen transfaunation after surgical correction of left
      sided displacement of the abomasum (LDA) in cows. DESIGN: Prospective clinical
      trial. ANIMALS: 20 multiparous cows with LDA. PROCEDURES: Cows with LDA were
      treated surgically (day 0). On days 0 (immediately after surgery) and 1, 10 cows
      each received 10 L of rumen fluid (transfaunated group) or 10 L of water (control
      group) via a stomach tube. Postoperative dietary dry-matter intake and milk yield
      of each cow were recorded daily for 5 days, beginning immediately after surgery.
      Blood and rumen fluid samples were collected prior to surgery and on days 1, 3,
      and 5 after surgery. Serum nonesterified fatty acid and beta-hydroxybutyrate
      concentrations were measured. Volatile fatty acid and ammonia concentrations and
      pH of rumen fluid were determined. Urine specimens were collected and tested for
      ketones at 8 AM and 4 PM. Cows with ketonuria were treated with 50% dextrose
      solution administered i.v. at the time ketonuria was first detected. Cows with
      ketonuria were treated twice daily until ketonuria resolved. RESULTS: All cows
      survived and completed their lactation. Daily and cumulative dry-matter intake
      and milk yield of cows in the transfaunated group were significantly greater than
      those of cows in the control group. Cows in the transfaunated group had
      significantly lower serum concentrations of beta-hydroxybutyrate and
      significantly lower acetate-to-propionate ratios in rumen fluid on day 1 after
      surgery, compared with cows in the control group. Cows that received transfaunate
      required a significantly lower total volume of dextrose administered i.v. than
      control cows. CONCLUSIONS AND CLINICAL RELEVANCE: Benefits of rumen
      transfaunation of cows after surgical correction of LDA included a lesser degree
      of ketonuria, greater feed intake, and higher milk yield, compared with
      nontransfaunated cows.

PMID- 15485055
TI  - Surgical advances in tonsillectomy: report of a roundtable discussion.

PMID- 15485054
TI  - West Nile virus infection in two alpacas.
AB  - A male alpaca acutely developed signs of anorexia and fever. Within 2 days,
      neurologic signs (head tremors and asymmetric ataxia) developed. West Nile virus
      (WNV) infection was considered a primary differential diagnosis on the basis of 6
      previous cases on nearby alpaca farms on which animals had similar clinical
      signs. Four days after the male alpaca became ill, a female alpaca from the same
      farm developed similar neurologic signs. In addition to anti-inflammatory and
      supportive treatments, both alpacas received a transfusion of llama plasma with
      antibodies against WNV Seven days after the onset of clinical signs, the female
      alpaca had made a full recovery; however, the more severely affected male died.
      West Nile virus infection was confirmed post mortem by use of reverse
      transcriptase-polymerase chain reaction assay and immunohistochemical staining.

PMID- 15485056
TI  - Getting better?

PMID- 15485057
TI  - What chance choice?

PMID- 15485058
TI  - Watching the Wakefields.

PMID- 15485059
TI  - Different Options.

PMID- 15485060
TI  - Prisoners are among the most vulnerable and least well-served of all people using
      mental health services.

PMID- 15485061
TI  - All it requires is for politicians to say: 'OK, it's been wrong--but we're going
      to put it right'.

PMID- 15485062
TI  - Psychiatry is all about stories--stories about our stories about the stories our
      clients tell us.

PMID- 15485063
TI  - Limiting the damage.

PMID- 15485064
TI  - Right, wrong and respect.

PMID- 15485065
TI  - Putting training into practice.

PMID- 15485066
TI  - Body, mind, spirit and soul.

PMID- 15485068
TI  - A quarter of service users can't use services because they can't afford the
      transport to get there.

PMID- 15485067
TI  - NICE guidelines.

PMID- 15485069
TI  - This life.

PMID- 15485070
TI  - Oslerisms.

PMID- 15485071
TI  - The ubiquitous urushiols Contact dermatitis from mango, poison ivy, and other
      "poison" plants. 1968.

PMID- 15485072
TI  - Mango: Hawaii's forbidden fruit.

PMID- 15485073
TI  - Rates for specific birth defects among native Hawaiians compared to whites,
      Hawaii 1986-2000.
AB  - Rates for many birth defects have not been identified for native Hawaiians. Using
      birth defects regstry data, the total major birth defect rate for whites was
      found to be 4.70% and for native Hawaiians was 4.75%. After adjusting for
      maternalage, the rates were lower among native Hawaiians for 40 (74.1%) of 54
      selected birth defects.

PMID- 15485074
TI  - The JABSOM Willed Body Donation Program, a unique medical educational experience.

PMID- 15485075
TI  - Your family history can save your life.

PMID- 15485076
TI  - A mini-forum on air breaks and O2 toxicity in clinical HBO2 therapy.

PMID- 15485077
TI  - Two differences in hyperbaric exposure.

PMID- 15485078
TI  - Central nervous system oxygen toxicity during routine hyperbaric oxygen therapy.

PMID- 15485079
TI  - How the Davis 2.36 ATA wound healing enhancement treatment table was established.

PMID- 15485080
TI  - Extension of oxygen tolerance by interrupted exposure.

PMID- 15485081
TI  - Incidence of oxygen toxicity during the treatment of dysbarism.
AB  - Oxygen (O2) toxicity may result from exposure to partial pressures of O2 above
      0.6ATA. Potential toxic exposure for divers occurs during the treatment of
      dysbarism. In the recompression chamber, PO2 may range from 0.9ATA to 3.3ATA
      depending upon the treatment table employed. This retrospective study examines
      the nature and incidence of O2 toxicity in 998 patients who underwent
      recompression treatment at our facility from 1983 through 2001. Only patients
      evaluated for diving related injury were considered for this study. Of 1189
      charts reviewed, 998 patients received recompression and were entered into this
      study. The total number of treatment exposures was determined as was the total
      number of O2 toxicity events characterized as either pulmonary or CNS, and
      patients were divided into male/female analysis. Overall incidence as well as the
      incidence for both toxicity types was determined, and their occurrence in both
      male and female patients was ascertained. 2166 recompressions were undertaken,
      449 female and 1717 male. The peak PO2 for these treatments ranged from 2.6ATA to
      2.9ATA. 155 O2 toxicity events occurred in 152 patients, 49 females and 103
      males. Three patients, 2 females and 1 male, had mixed events. Incidence of an O2
      toxic event = 7.0 per 100 recompressions. Incidence of pulmonary toxicity overall
      = 5.0 per 100 recompressions, while CNS events = 2.0 per 100 recompressions with
      overall seizure rate = 0.6 per 100 recompressions. In females, pulmonary toxicity
      rate = 6.9 per 100 recompressions, CNS toxicity rate = 4.4 per 100 recompressions
      with seizures occurring at 1.3 per 100 recompressions. In males, pulmonary
      toxicity rate = 4.6 per 100 recompressions, CNS toxicity rate = 1.4 per 100
      recompressions, and seizures at 0.4 per 100 recompressions.

PMID- 15485082
TI  - Short-term vasomotor adjustments to post immersion dehydration are hindered by
      natriuretic peptides.
AB  - Many studies have described the physiology of water immersion (WI), whereas few
      have focused on post WI physiology, which faces the global water loss of the
      large WI diuresis. Therefore, we compared hemodynamics and vasomotor tone in 10
      trained supine divers before and after two 6h sessions in dry (DY) and head out
      WI environments. During each exposure (DY and WI) two exercise periods (each one
      hour 75W ergometer cycling) started after the 3rd and 5th hours. Weight losses
      were significant (-2.24 +/- 0.13 kg and -2.38 +/- 0.19 kg, after DY and WI,
      respectively), but not different between the two conditions. Plasma volume was
      reduced at the end of the two conditions (-9.7 +/- 1.6% and -14.7 +/- 1.6%,
      respectively; p < 0.05). This post-WI decrease was deeper than post DY (p <
      0.05). Cardiac output (CO) and mean arterial blood pressure were maintained after
      the two exposures. Plasma levels of noradrenaline, antidiuretic hormone and ANP
      were twofold higher after WI than after DY (p < 0.05). After DY total peripheral
      resistances (TPR) were increased (p < 0.05) and heart rate (HR) was reduced (p <
      0.05). After WI there was a trend for a decrease in stroke volume (p = 0.07) with
      unchanged TPR and HR, despite more sizeable increases in plasma noradrenaline and
      vasopressin than after DY. We hypothesized that the higher levels of plasma
      natriuretic peptides after WI were likely counteracting the dehydration-required
      vasomotor adjustments.

PMID- 15485083
TI  - Hyperbaric oxygen treatment time for cyclophosphamide induced cystitis in rats.
AB  - The aim of this study was to evaluate the prophylactic potential of hyperbaric
      oxygenation treatment and the timing of hyperbaric oxygen (HBO2) therapy for
      cyclophosphamide-(CYP) induced cystitis in rats. Forty male Sprague-Dawley rats
      were divided into 5 groups. Four groups received a single dose of CYP (100
      mg/kg.) intraperitoneally (i.p.) at the same time (group 1 served as the
      control). Group 2 received CYP only; group 3 received HBO2 treatment (2.8
      atmospheres absolute, 90 minutes, twice daily) before and the day after CYP.
      Group 4 received HBO2 before and on the day of CYP administration. Group 5
      received HBO2 on the day of and the day after CYP. CYP injection resulted in
      severe cystitis. Prophylactic HBO2 treatment did not prevent the severe cystitis.
      After CYP injection, however, HBO2 treatment attenuated CYP-induced hemorrhagic
      cystitis in rats. Hyperbaric oxygen has a beneficial effect on repairing and
      healing bladder damage, though it does not function to prevent CYP-induced
      hemorrhagic cystitis.

PMID- 15485084
TI  - Leukotriene-B4 concentrations in breathing condensate before and after simulated
      deep dives.
AB  - During diving the respiratory tract is exposed to occupational hazards (increased
      oxygen partial pressure, pulmonary vessel engorgement during submersion, inert
      gas micro embolism during decompression). Leukotriene-B4 [LTB4] concentrations in
      the exhaled breath mirrors the inflammatory activity of the airways if the
      respiratory tract has been exposed to occupational hazards. In this study LTB4
      concentrations in the exhaled breath and spirometry data obtained before and
      after simulated dives helped to elucidate any contributions by hyperbaric
      exposure to impaired lung function and to separate effects of ambient pressure
      from those of submersion and increased oxygen partial pressure. Thirty two
      healthy subjects carried out dives in a hyperbaric chamber using a cross over
      design to 600 kPa ambient pressure with and without submersion and a dry exposure
      to pure oxygen at 120 kPa ambient pressure (durations: 43 min). Pre-dive and four
      hours after surfacing the exhaled breath was collected non-invasively. Condensate
      was measured by a standard enzyme immuno-assay for LTB4 in parallel with lung
      function values (FVC, FEV1, MEF 25-75). Pre-exposure baseline values of LTB4
      concentrations and lung function values were in the normal range. Post-exposure
      values did not differ significantly from the baseline values. The data gave no
      evidence of any inflammatory activity in the subjects' airways after hyperbaric
      exposure.

PMID- 15485085
TI  - Superoxide dismutase responds to hyperoxia in rat hippocampus.
AB  - The brain's anti-oxidant response to highly elevated oxygen (O2) partial
      pressures is poorly understood. In this study we hypothesized that hyperbaric O2
      (HBO2) would stimulate superoxide dismutase (SOD) transcription in the oxidative
      stress-sensitive rat hippocampus and measured the time course and extent of the
      changes in hippocampal mRNA for all three SOD isoforms and total SOD enzyme
      activity. Comparisons were made between exposures to 2 hours of 1 atmosphere
      pressure normobaric oxygen (NBO); 2 hours of 3 atmospheres HBO2; and room air.
      Hyperoxia (HBO2 > NBO) was associated with statistically significant increases in
      transcript levels of the antioxidant enzymes SOD2 (MnSOD) and SOD3 (EC-SOD) at 6
      and 18 hours but not SOD1 (Cu, Zn SOD) respectively. Hyperoxia, however, did not
      affect total hippocampal SOD activity measured at 6 and 24 hours, indicating that
      the mRNA responses were necessary to maintain the anti-oxidant enzyme activity
      after oxidative stress.

PMID- 15485086
TI  - A deep stop during decompression from 82 fsw (25 m) significantly reduces bubbles
      and fast tissue gas tensions.
AB  - In spite of many modifications to decompression algorithms, the incidence of
      decompression sickness (DCS) in scuba divers has changed very little. The success
      of stage, compared to linear ascents, is well described yet theoretical changes
      in decompression ratios have diminished the importance of fast tissue gas
      tensions as critical for bubble generation. The most serious signs and symptoms
      of DCS involve the spinal cord, with a tissue half time of only 12.5 minutes. It
      is proposed that present decompression schedules do not permit sufficient gas
      elimination from such fast tissues, resulting in bubble formation. Further, it is
      hypothesized that introduction of a deep stop will significantly reduce fast
      tissue bubble formation and neurological DCS risk. A total of 181 dives were made
      to 82 fsw (25 m) by 22 volunteers. Two dives of 25 min and 20 min were made, with
      a 3 hr 30 min surface interval and according to 8 different ascent protocols.
      Ascent rates of 10, 33 or 60 fsw/min (3, 10, 18 m/min) were combined with no
      stops or a shallow stop at 20 fsw (6 m) or a deep stop at 50 fsw (15 m) and a
      shallow at 20 fsw (6 m). The highest bubbles scores (8.78/9.97), using the
      Spencer Scale (SS) and Extended Spencer Scale (ESS) respectively, were with the
      slowest ascent rate. This also showed the highest 5 min and 10 min tissue loads
      of 48% and 75%. The lowest bubble scores (1.79/2.50) were with an ascent rate of
      33 fsw (10 m/min) and stops for 5 min at 50 fsw (15 m) and 20 fsw (6 m). This
      also showed the lowest 5 and 10 min tissue loads at 25% and 52% respectively.
      Thus, introduction of a deep stop significantly reduced Doppler detected bubbles
      together with tissue gas tensions in the 5 and 10 min tissues, which has
      implications for reducing the incidence of neurological DCS in divers.

PMID- 15485087
TI  - Report of the use of hyperbaric oxygen therapy (HBO2) in an unusual case of
      secondary infertility.
AB  - We report the use of hyperbaric oxygen therapy (HBO2) in the treatment of an
      unusual case of secondary infertility. The patient had failed to conceive after a
      1-year period of in-vitro fertilization, during which oral sildenafil had also
      been administered. However she became pregnant after an IVF cycle and the use of
      adjunctive HBO2 and sildenafil, which was administered intravaginally on this
      occasion. There is currently very little evidence to support the use of HBO2 in
      this context. The possible mechanisms of action of HBO2 in this case are
      discussed.

PMID- 15485088
TI  - The effect of hyperbaric oxygen on human oral cancer cells.
AB  - Discoveries of the beneficial cellular and biochemical effects have strengthened
      the rationale for the administration of hyperbaric oxygen therapy (HBO2) as an
      adjunctive therapy for the treatment of osteoradionecrosis (ORN). Malignancies,
      however, are considered a contraindication for HBO2 because of the possible tumor
      promoting effects. The aim of this study was to examine the effects of HBO2
      therapy on tumor weight, and to measure the progression of apoptosis and tumor
      cell proliferating activity in a cultured human oral cancer cell line. Twenty 5
      week-old male NODscid mice underwent daily HBO2 of 2.5 atm abs, 90 minutes for 20
      treatments. The control group, n = 20, did not undergo HBO2 and tumor weight,
      apoptosis index, and proliferating activity parameters were compared between the
      two groups. The results showed no significant differences (p < 0.05) in the whole
      body weights, tumor weights, apoptotic index or proliferating activity index
      between the two groups. By using the apoptosis and proliferating activity assays
      which were better indicators of tumor cell growth than tumor weight alone, our
      results suggest that the clinical application of HBO2 does not promote the growth
      or proliferation of human oral cancer cells.

PMID- 15485089
TI  - Incidence of abnormal cerebral findings in the MRI of clinically healthy divers:
      role of a patent foramen ovale.
AB  - BACKGROUND: To investigate incidence and number of abnormal cerebral
      hyperintensities (ACFs) in Magnet Resonance Imaging (MRI) and its relation to a
      patent foramen ovale (PFO) in divers with no history of decompression illness.
      METHODS: Cohort study on 50 divers (21-5500 dives). MAIN OUTCOME MEASURES:
      Incidence and number of ACFs visualized by cranial MRI and presence and size of a
      PFO as documented by echocardiography and transcranial Doppler ultrasound (TCD)
      with echocontrast. RESULTS: A total of 137 ACFs was found in the 50 subjects,
      with a significant correlation between the number of dives and number of ACFs (r
      = 0.28; p < 0.05); but after correction for age, the remaining correlation (r =
      0.15) did not reach significance. In 18 divers, a PFO was present by either the
      application of echocardiography or TCD; in 12 divers, the PFO was of high
      hemodynamic relevance. Ten of 18 divers with a PFO had at least one ACF, while in
      the remaining 32 divers, only 14 had at least one ACF (56% versus 44%, p = NS).
      Seven of 14 divers (50%) with 4 ACFs had a PFO, compared to 11 of 36 (31%) with
      less than 4 ACFs (p = NS). CONCLUSION: In this cohort of healthy divers, in
      contrast to an earlier report, no significant association was found between PFO
      presence and incidence or number of ACFs.

PMID- 15485090
TI  - Feto-maternal immune interaction at the placental level.
AB  - A special interaction is established during pregnancy between the maternal immune
      system and fetal cells to allow the survival and the normal growth of the fetus.
      Fetal cells expressing paternal alloantigens are not recognized as foreign by the
      mother because of an efficient anatomic barrier and a local immunosuppression
      determined by the interplay of locally produced cytokines, biologically active
      molecules and hormones. A special balance between TH1 and TH2 lymphocytes has
      also been observed at the feto-maternal barrier that contribute to control the
      immune response at this level. An important role is played by trophoblast cells
      that act as a physical barrier forming a continuous layer and exert
      immunomodulatory function. Trophoblast cells have also been shown to express
      regulators of the complement system and to downregulate the expression of HLA
      antigens. Dysfunction of these cells leads to morphological and functional
      alterations of the feto-maternal barrier as well as to hormonal and immune
      imbalance and may contribute to the development of pathologic conditions of
      pregnancy, such as recurrent spontaneous abortions. Efforts are still needed to
      better understand the physiology of the feto-maternal interaction and the
      pathogenetic mechanisms responsible for tissue damage in pathologic conditions of
      pregnancy.

PMID- 15485091
TI  - Cytokines in recurrent miscarriage.
AB  - Cytokines act at all stages of pregnancy from implantation to parturition. This
      review examines their relevance in recurrent miscarriage. However, recurrent
      miscarriage may be due to an inherently abnormal embryo (e.g., chromosomal
      abberations) or maternal factors (e.g., uterine anomalies or antiphospholipid
      antibodies). In the former, cytokines are not causative, but may be part of the
      mechanism of abortion. In the antiphospholipid syndrome, cytokines such as
      TNFalpha and IL-6 may be responsible for the associated thrombosis. Hence, an
      appropriate cytokine milieu could be responsible for whether the antibodies are
      pathogenic or merely an epiphenomenon. Natural killer cells seem to have a key
      role in immunosurveillance of the invading trophoblast. However, if activated by
      TNFalpha, natural killer cells may induce apoptosis in the trophoblast possibly
      leading to miscarriage. This action is inhibited by TGFbeta. Early ultrasound
      scanning and embryoscopy have revealed structural anomalies in karyotypically
      normal embryos which have terminated in first trimester missed abortion.
      Teratogens such as cyclophosphamide cause fetal demise by excessive apoptosis.
      Excessive apoptosis may be mediated by TNFalpha, TGFbeta and other cytokines. GM
      CSF has been reported to prevent teratogenesis in laboratory animals. Both
      immunomodulation and hormonal support (progesterone or hCG supplements) have been
      used to improve the live birth rate in recurrently aborting women. Each may
      modulate the balance between various cytokines. Although neither hormonal support
      or immunopotentiation have been proven to be beneficial, the results and the role
      of cytokines themselves can only be assessed in trials of karyotypically normal
      embryos.

PMID- 15485092
TI  - Sex hormones influence on the immune system: basic and clinical aspects in
      autoimmunity.
AB  - Sex hormones seem to play an important role as modulators of the autoimmune
      disease onset/perpetuation. Generally, steroid hormones are implicated in the
      immune response, with estrogens as enhancers at least of the humoral immunity and
      androgens and progesterone (and glucocorticoids) as natural immunosuppressors.
      Synovial fluid levels (SF) of proinflammatory estrogens relative to androgens are
      significantly elevated in both male and female rheumatoid arthritis (RA)
      patients, as compared to controls, which is most probably due to increase of
      local enzymatic aromatase activity. Serum levels of estrogens have been found
      altered in RA patients, particularly estradiol in man. Thus, available steroid
      prehormones are rapidly converted to proinflammatory estrogens in the synovial
      tissue in the presence of inflammatory cytokines (i.e., TNFalpha, IL-1, IL-6).
      The increased estrogen concentrations observed in RA SF of both sexes are
      characterized mainly by the hydroxylated forms, in particular, 16alpha
      hydroxyestrone, showing a mitogenic tumor growth stimulating role. Altered serum
      hydroxylated estrogens have been found also in serum of systemic lupus
      erythematosus (SLE) patients. As a matter of fact, our recent studies indicate
      that 17-beta estradiol (E2) clearly enhanced the expression of markers of cell
      growth and proliferation, whereas testosterone (T) induced an increase of markers
      indicating DNA damage and apoptosis. In particular, our data further shows that
      the enhancing role of estrogens on immune/inflammatory response is exerted by
      activating the NFkB complex pathway. In conclusion, locally increased estrogens
      (i.e., synovial tissue in RA or skin in SLE) might exert activating effects on
      cell proliferation, including macrophages and fibroblasts, suggesting new roles
      for estrogens in autoimmunity.

PMID- 15485093
TI  - Progesterone supplement in pregnancy: an immunologic therapy?
AB  - One of the most interesting functions of the placenta is the regulation of the
      maternal immune response such that the fetal semi-allograft is tolerated during
      pregnancy. Trophoblasts are presumed to be essential to this phenomenon because
      they lie at the maternal-fetal interface, where they are in direct contact with
      cells of the maternal immune system. Trophoblasts do not express classic major
      histocompatibility complex (MHC) class II molecules. Surprisingly,
      cytotrophoblasts express more HLA-G, a MHC class Ib molecule, as they invade the
      uterus. Progesterone plays an important role in postovulatory regulation of the
      menstrual cycle. If fertilization occurs, progesterone supports implantation of
      the ovum and maintains the pregnancy. Progesterone has been named the 'hormone of
      pregnancy', because in preparing the endometrium for embryo implantation and
      facilitating endometrial development, it is critical to the very survival of a
      pregnancy. In addition, this key hormone inhibits the rejection of T cell
      mediated tissue and also decreases myometrial activity and sensitivity throughout
      pregnancy. The cellular actions of progesterone are mediated through
      intracellular progesterone receptors (PRs), which are well studied gene
      regulators, not express classic major histocompatibility complex. The more used
      paradigm is relative to the alteration of relationship TH1/TH2, but the
      complexity of the respective distributions of cytokines at the materno-fetal
      interface, strongly suggest that, as useful as it certainly was for a while, the
      Th1/Th2 paradigm must now be considered as an oversimplification. Rather, the
      existing data point to sequential windows and are suggestive of a system where an
      extreme complexity is allied to very precise timing and tuning. They also suggest
      that the materno-fetal relationship is not simply maternal tolerance of a foreign
      tissue, but a series of intricate mutual cytokine interactions governing
      selective immune regulation and also control of the adhesion and vascularization
      processes during this dialogue. However, as shifting the immune response toward
      the Th2 pattern (IL-4, IL-5, IL-6) may benefit the fetus, whereas development of
      proinflammatory Th1 cells (secreting IL-2, IFN g, TNF a) may be harmful. Now we
      are working to open comprise the precise behaviour of NK populations, with the
      hope of obtaining a diagnostic test of the condition of abortion from
      'immunological causes'.

PMID- 15485094
TI  - Autoantibodies associated with reproductive failure.
AB  - Autoimmune factors are involved in some of the cases of reproductive failure.
      These factors entail several autoantibodies, especially in patients having
      systemic lupus erythematosus (SLE) or the antiphospholipid syndrome (APS). These
      autoantibodies include mainly antibodies directed to phospholipid such as
      cardiolipin, phosphatidylserine, phosphatidylethanolamine or phospholipids
      binding glycoproteins such as beta2glycoprotein-I, annexin V, prothrombin and
      protein-Z. There are also some other autoantibodies directed to laminin-I,
      thromboplastin, mitochondrial antibodies of the M5 type, corpus luteum,
      prolactin, poly (ADP-ribose), thyroglobulin and more, which were also found in
      SLE or APS patients with reproductive failure. Moreover, the presence of
      additional autoantibodies directed to actin, enolase, cubilin and others, needs
      further investigation to support a firm association to reproductive failure in
      women. Future studies are likely to help to determine and expand the number of
      autoantibodies screened in these patients, as well as by the use of proteomics
      technology, to determine peptides resembling the epitope specificities associated
      with the specific clinical manifestations.

PMID- 15485095
TI  - Antiphospholipid antibodies as cause of pregnancy loss.
AB  - Antiphospholipid antibodies detected by lupus anticoagulant, anticardiolipin or
      anti-beta2 glycoprotein I assays were associated with fetal loss. Rather than
      being diagnostic tools only, antiphospholipid antibodies are thought to be
      pathogenic. The strongest demonstration of their pathogenic role lies in the
      ability to induce fetal resorptions--the experimental equivalents of the human
      fetal losses--when passively infused in pregnant naive animals. However, still
      debated is how the antibodies might induce the obstetrical manifestations.
      Thrombotic events at the placental levels might be related to endothelial cell
      activation, inhibition of protein C/S system and fibrinolysis as well as to
      Annexin V displacement. However, the thrombophilic state apparently cannot
      explain all the miscarriages and a direct antibody-mediated damage on the
      trophoblast has been suggested. During differentiation to syncytium, trophoblasts
      express cell membrane anionic phospholipids that can bind beta2 glycoprotein I,
      the main cationic phospholipid binding protein recognized by the antiphospholipid
      antibodies. Adhered beta2-glycoprotein I might be recognized by the antibodies
      that, once bound, strongly interfere with in vitro trophoblast cell maturation so
      resulting in a defective placentation. These mechanisms have been suggested to
      play a role in early fetal loss, while thrombotic events would be responsible for
      miscarriages late in the pregnancy.

PMID- 15485096
TI  - Celiac disease and inflammatory bowel disease in pregnancy.
AB  - An adverse influence on reproductive life and obstetric complications are known
      to occur in women with celiac disease (clinical and subclinical disease) or
      inflammatory bowel diseases. Treatment can improve the pregnancy outcome;
      therefore, it is advisable that a clinical evaluation is performed by a joint
      team of obstetricians, internists and surgeons. The preconception clinical
      evaluation of the affected women is useful to focus on the different clinical
      aspects of the disease and to indicate specific therapeutic strategies. In this
      study a review of the literature regard to celiac disease and inflammatory bowel
      disease in pregnancy is presented.

PMID- 15485097
TI  - Pregnancy, microchimerism and autoimmunity: an update.
AB  - The presence of a small population of cells or DNA in one individual that derives
      from another genetically distinct person is referred to as microchimerism; this
      process may occur in course of pregnancy from mother to fetus, and vice versa.
      The clinical similarities between some features of autoimmune diseases and the
      chronic graft versus host disease, the increased incidence of autoimmune diseases
      observed in women after childbearing age, and the long-term persistence of
      microchimerism have raised the hypothesis that microchimerism could be involved
      in the pathogenesis of autoimmune diseases. To assess the possible relationship
      between pregnancy and the incidence of systemic sclerosis we performed a hospital
      based case-control study. Our results, indicating a reduced risk for systemic
      sclerosis in women who had been pregnant in comparison with women who had not,
      seem to indicate that pregnancy is not a risk factor for systemic sclerosis.

PMID- 15485098
TI  - Antiphosphatidylserine antibodies and reproductive failure.
AB  - Some cases of reproductive failure with autoimmune background are characterized
      by the involvement of autoantibodies. This occurs mainly in patients having
      systemic lupus erythematosus or antiphospholipid syndrome. The autoantibodies
      associated with reproductive failure include: a) antibodies which directly bind
      phospholipid (e.g., cardiolipin, phosphatidylserine, phosphatidylethanolamine);
      b) antiphospholipid Abs which bind the phospholipid via phospholipid-binding
      glycoproteins such as beta2glycoprotein-I, annexin V and prothrombin; c)
      autoantibodies directed to laminin-I, actin, thromboplastin, the corpus luteum,
      prolactin, poly (ADP-ribose), thyroglobulin and mitochondrial antibodies of the
      M5 type. This paper will focus on the association of antiphosphatidylserine
      autoantibodies and reproductive failure. Future studies are likely to help to
      identify peptides resembling the epitope specificities associated with the
      specific clinical manifestations.

PMID- 15485099
TI  - Pregnancy in patients with rheumatic diseases: psychological implication of a
      chronic disease and neuropsychological evaluation of the children.
AB  - As a consequence of the general improvement in the diagnosis and management of
      rheumatic diseases, patients achieve a better quality of life, with the
      possibility of a normal family life including one or more pregnancies. It is
      important, therefore, to consider the psychological aspects of these mothers'
      life and the influence of their chronic disease on their children is development.
      Several papers have reported the impact of systemic lupus erythematosus (SLE) on
      the quality of life. They found higher incidence of anxiety (from 15 to 45%) and
      depression (from 25 to 47%) compared to the general population. We have
      investigated the psychological influence of SLE on family planning, and we
      observed that it can interfere with physiological phenomena such as parenthood
      and the upbringing of children. The children of lupus mothers have a normal
      intelligence level for their age. What is emerging, however, is an increased
      incidence of learning disabilities compared to the general population. This
      observation suggests the importance of an early neuropsychological examination,
      in order to identify the children needing particular care. Therefore,
      psychological support seems to be an important help in the counseling of patients
      with rheumatic disease and in the future life of their children.

PMID- 15485100
TI  - Autoimmunity, infertility and assisted reproductive technologies.
AB  - Despite strongly held opinions, a trustworthy scientific basis for most
      statements about autoimmunity, autoimmune diseases and assisted reproductive
      technologies (ART) does not exist. It is not likely that autoimmunity causes
      infertility, nor that patients with autoimmune diseases are unusually infertile.
      When carefully monitored in selected patients, ART does not appear to harm
      patients who have pre-existing autoimmune diseases, but the ovarian
      hyperstimulation syndrome and multiple gestation pregnancies impart independent
      risks. Stable autoimmune diseases without major organ damage probably do not
      affect the outcomes of ART pregnancies. Children born of ART pregnancies are
      apparently normal at birth, whether or not the genetic or birth mother has
      autoimmune disease, but long-term follow-up is not available. Male fertility is
      probably not altered by autoimmune disease. Fiscal, ethical and moral issues
      related to ART in patients with autoimmune diseases are beyond the scope of this
      discussion but remain important.

PMID- 15485101
TI  - Ovarian failure in systemic lupus erythematosus patients treated with pulsed
      intravenous cyclophosphamide.
AB  - Pulsed intravenous cyclophosphamide is considered as standard therapy for lupus
      nephritis and several other severe manifestations of systemic lupus erythematosus
      (SLE). While the response rate to intravenous cyclophosphamide is substantial,
      concern has arisen about its toxicity. In addition to increased susceptibility to
      infection, bone marrow suppression, alopecia, hemorrhagic cystitis and
      malignancy, ovarian failure is an important side effect associated with the use
      of cyclophosphamide. Prior research on cyclophosphamide-treated women has
      consistently demonstrated that the risk of sustained amenorrhea depends on the
      age of the patient and the cumulative dose received. Sustained amenorrhea is
      difficult to avoid in women 32 years or older, even with very short intravenous
      cyclophosphamide courses. Younger women seem to have a substantially lower
      incidence of ovarian failure, but this side effect may be far more problematic
      for these patients. In these young women the risk may be modulated by the prior
      SLE disease duration, the presence of anti-U1RNP antibodies and anti-Ro
      antibodies. Co-treatment with gonadotropin-releasing hormone agonists may
      preseserve the future fertility and ovarian function in young women. Ovarian
      banking before administration of cyclophosphamide should be considered in
      selected patients.

PMID- 15485102
TI  - Evaluation of systemic lupus erythematosus activity during pregnancy.
AB  - Due to our increasing knowledge on the pathophysiological basis of autoimmunity
      and the development of combined medical-obstetric clinics, pregnancy is becoming
      common among women with systemic lupus erythematosus (SLE). However, whether
      lupus worsens during pregnancy continues to be a controversial issue. SLE
      assessment during pregnancy is sometimes difficult due to physiological changes
      during this period, and common tools for measuring lupus activity during
      pregnancy were not available until recently. Several lupus activity scales in
      common use have been adapted for pregnancy [systemic lupus erythematosus in
      pregnancy activity index (SLEPDAI), modified lupus activity measurement (m-SLAM)
      and lupus activity index in pregnancy (LAI-P)]. All of them take into account the
      influence of pregnancy on clinical manifestation and common biochemical tests.
      LAI-P also accounts for specific manifestations of antiphospholipid syndrome in
      order not to score them as due to SLE activity. LAI-P has recently been validated
      for use in SLE pregnancy and could be used in future studies. However, daily
      assessment and management of individual pregnant women with lupus still relies on
      the clinical skills of attending physicians.

PMID- 15485103
TI  - The management of pregnant patients with antiphospholipid syndrome.
AB  - Recurrent pregnancy loss is now considered a treatable clinical condition
      associated with antiphospholipid antibodies. The management of pregnant patients
      with antiphospholipid syndrome is mainly based on the use of
      antiaggregant/anticoagulant agents (with aspirin and heparin) to prevent
      thrombosis in the uteroplacental circulation. Interventions with these drug
      therapies and monitored pregnancy have increased fetal survival.

PMID- 15485104
TI  - Prospective study of systemic lupus erythematosus pregnancies.
AB  - Different study designs have yielded different results on the effect of pregnancy
      on systemic lupus erythematosus (SLE) disease activity. Using the patient as her
      own control, and using nonpregnant SLE patients as controls, we have found flares
      to be more common in pregnancy. In SLE pregnancies followed prospectively at one
      center, we have found that preterm birth is the most frequent adverse event.
      Pregnancy loss occurred in 14%. Active SLE contributes to both preterm birth and
      to pregnancy loss. In addition, even in a first pregnancy, the presence of the
      lupus anticoagulant is associated with an increased risk of pregnancy loss.

PMID- 15485105
TI  - Pregnancy in rare autoimmune rheumatic diseases: UCTD, MCTD, myositis, systemic
      vasculitis and Bechet disease.
AB  - The physiological adaptation of the immune system to pregnancy can potentially
      affect the course of all autoimmune rheumatic diseases (ARD), conversely the
      autoimmune processes characteristic of these conditions may compromise the foetal
      outcome. Unfortunately, very few reports on pregnancy outcome in patients with
      rare ARD are available. In this paper, we briefly review the data published until
      now on these disorders. Some general guidelines which were elaborated for more
      prevalent ARD seem to be valid also for such rare conditions: 1) patients should
      be correctly informed on the risk of becoming pregnant; 2) pregnancies should be
      planned when the disease is in remission since it increases the probability of
      successful maternal and foetal outcome; 3) patients should be regularly monitored
      during gestation and postpartum by a multidisciplinary team including
      rheumatologist, obstetrician, and neonatologist; 4) in the case of disease
      relapse an adequate treatment, even aggressive if necessary, should be
      recommended since active disease can be more detrimental for foetus than drugs;
      5) pregnancies complicated by the onset of rare ARD have a particularly severe
      prognosis; in these cases a prompt treatment and very close clinical surveillance
      are indicated.

PMID- 15485106
TI  - Pregnancy in patients with rheumatic diseases: obstetric management and
      monitoring.
AB  - The obstetric management of the pregnant rheumatic patient is largely dictated by
      the specific disease and the degree to which it is associated with recognizable
      and treatable adverse obstetric outcomes, maternal or fetal. This review will
      cover the obstetric management of women with systemic lupus erythematosus (SLE),
      antiphospholipid syndrome (APS), rheumatoid arthritis (RA) and systemic sclerosis
      (SSc). Most experts agree that a co-ordinated management effort on the part of
      obstetricians and rheumatologists will likely yield the optimal achievable
      results.

PMID- 15485107
TI  - Anaesthesiological aspects of pregnancy in patients with rheumatic diseases.
AB  - The anaesthesiologist facing a pregnant woman with rheumatic disease is caught
      between a rock (the problems of general anaesthesia, i.e., the difficult airway
      and/or the cardiopulmonary dysfunctions that can worsen the response to general
      anaesthetics or to mechanical ventilation) and a hard place (the problems of loco
      regional anaesthesia, i.e., intrinsic or iatrogenic haemostatic dysfunctions,
      potentially causing spinal haematoma, the most threatening complication).
      However, the term lupus anticoagulant is a misnomer and in the absence of an
      underlying coagulation deficit or anticoagulant therapy, the anaesthesiologist
      can usually guarantee epidural analgesia for vaginal delivery to parturients
      affected by rheumatic diseases (so contributing to the decrease of the caesarean
      section rate) and, in case of a caesarean section for medical or obstetrical
      indications, often he can perform a loco-regional anaesthesia, which determines a
      substantially lower maternal mortality rate. It is very important to adopt a
      multidisciplinary approach comprising an antepartum team evaluation (to be
      performed at 36th gestational week) of the basal condition of the parturient:
      together, the obstetrician, the rheumatologist and the anaesthesiologist should
      define the type of delivery. We will also try to define the haemostatic safety
      criteria to be fulfilled for administration of an epidural analgesia to a
      parturient affected by rheumatic disease.

PMID- 15485108
TI  - Short and long-term maternal outcomes in patients with phospholipid antibodies.
AB  - By definition patients with phospholipid antibody (aPL) syndrome develop clinical
      thrombotic events and frequently fail to complete pregnancy successfully.
      Pregnancy is a physiological state known to trigger clinical thrombosis in aPL
      syndrome patients. This paper will review the short-term effects of pregnancy on
      aPL patients as well as the long-term outcome of aPL women who have attempted
      pregnancy.

PMID- 15485109
TI  - Neonatal lupus syndromes.
AB  - The neonatal lupus syndromes (NLS), while quite rare, carry significant mortality
      and morbidity in cases of cardiac manifestations. Although anti-SSA/Ro-SSB/La
      antibodies are detected in > 85% of mothers whose fetuses are identified with
      congenital heart block (CHB) in a structurally normal heart, when clinicians
      applied this testing to their pregnant patients, the risk for a woman with the
      candidate antibodies to have a child with CHB was at or below 1 in 50. While the
      precise pathogenic mechanism of antibody-mediated injury remains unknown, it is
      clear that the antibodies alone are insufficient to cause disease and fetal
      factors are likely contributory. In vivo and in vitro evidence supports a
      pathologic cascade involving apoptosis of cardiocytes, surface translocation of
      Ro and La antigens, binding of maternal autoantibodies, secretion of profibrosing
      factors (e.g., TGFbeta) from the scavenging macrophages and modulation of cardiac
      fibroblasts to a myofibroflast scarring phenotype. The spectrum of cardiac
      abnormalities continues to expand, with varying degrees of block identified in
      utero and reports of late onset cardiomyopathy (some of which display endocardial
      fibroelastosis). Moreover, there is now clear documentation that incomplete
      blocks (including those improving in utero with dexamethasone) can progress
      postnatally, despite the clearance of the maternal antibodies from the neonatal
      circulation. Better echocardiographic measurements which identify first degree
      block in utero may be the optimal means of approaching pregnant women at risk.
      Prophylactic therapies, including treatment with intravenous immunoglobulin,
      await larger trials. In order to achieve advances at both the bench and bedside,
      national research registries established in the US and Canada are critical.

PMID- 15485110
TI  - European register of babies born to mothers with antiphospholipid syndrome.
AB  - This prospective multicentric register was initiated by the European Forum of
      Antiphospholipid Antibodies (APL) in 2003 after approval by local ethic
      committees. This register allows the investigation of infants after written
      informed parental consent. It collects mothers' clinical pattern of
      antiphospholipid syndrome (APS), course and outcome of pregnancy, treatment and
      immunological status. For the babies, clinical and immunological examinations are
      performed at birth; neurodevelopmental conditions followed up to five years. A re
      evaluation of lupus anticoagulant (LA), anticardiolipin (ACL) or other antibodies
      will be done if they are positive at birth to follow their kinetics. A
      descriptive and a case control study of babies with versus without APL at birth
      will be possible after the inclusion of 300 cases.

PMID- 15485111
TI  - Neonatal outcome in patients with rheumatic disease.
AB  - Rheumatic autoimmune diseases have a higher prevalence in women, particularly
      during their childbearing age. Due to improved management, an increasing number
      of patients plan and carry out one or more pregnancies. Therefore, a growing
      interest is being paid to the possible consequences of maternal disease and
      associated treatment on the fetus and newborn infant. If maternal disease is
      characterized by the presence of IgG isotype autoantibodies, these can cross the
      placenta with possible antibody-mediated damage to the fetus. This is typically
      the case of the so called neonatal lupus erythematosus (NLE); a similar mechanism
      has been shown in infants of patients with immune thrombocytopenic purpura (ITP)
      and, less frequently, in those from mothers with antiphospholipid syndrome (APS).
      Indeed, this last condition is often responsible for placental, rather than
      neonatal, pathology. In addition, immunosuppressive and other drugs administered
      to the mothers during pregnancy and lactation might affect the fetal and neonatal
      immune system development. Finally, mothers disease and/or treatment could be
      related to neuropsychological alteration reported in some of their children.

PMID- 15485112
TI  - Risk factors for osteoporosis in female patients with systemic lupus
      erythematosus.
AB  - In the last years it has been recognized that patients with systemic lupus
      erythematosus (SLE) are at high risk of osteoporosis (OP) and fractures, both
      occurring through disease-specific (chronic arthritis, reduced physical activity,
      induction of cytokines promoting bone resorption, renal impairment, endocrine
      factors) and nondisease-specific mechanisms (sunshine avoidance with consequent
      vitamin D deficiency, glucocorticoids, immunosuppressants and chronic
      anticoagulants). Regarding anticoagulants, subcutaneous heparin is crucial
      against the risk of recurrent thromboembolism or pregnancy loss, specifically in
      patients with SLE and anti-phospholipid syndrome (APS). Thus heparin-induced OP
      represents one of the hazards of this treatment, first because heparin must be
      used long-term and secondly because pregnancy and lactation themselves may
      predispose to OP and fractures. Current data suggest the use of prophylaxis with
      calcium and vitamin D in all patients treated with heparin during pregnancy.
      Nevertheless glucocorticoid-induced OP (GIOP) is considered the most serious risk
      factor for OP and fractures in SLE patients. All guidelines recommend general
      measures and supplementation with calcium and vitamin D in all patients. However
      when considering premenopausal patients, there is no generally recommended
      treatment. Bisphosphonates, which are considered the first choice therapy for the
      prevention and treatment of GIOP, should be used 'cautiously' in these patients.
      Therefore the potential risks and lack of efficacy data on fracture risk
      reduction in premenopausal patients must be weighed against their proven efficacy
      in postmenopausal patients.

PMID- 15485113
TI  - IVIG in APS pregnancy.
AB  - For more than two decades, the intravenous administration of high doses of IgG
      pooled from the plasma of healthy donors (immune globulin therapy, also known as
      'IVIG') has benefited patients with a variety of autoimmune disorders. A
      potential therapeutic role of IVIG in the prevention of thrombosis and of
      miscarriages in antiphospholipid syndrome (APS) has been postulated. Multicenter
      randomized controlled trials attempted to define the role of IVIG in preventing
      pregnancy complications in APS indicate that simple anticoagulation could not be
      completely satisfactory, and certain patient subgroups might take advantage of
      IVIG therapy alone or in combination with heparin.

PMID- 15485114
TI  - Any increased risk of autoimmune disease?
AB  - Autoimmune diseases such as systemic lupus erythematosus (SLE) are known to have
      a strong genetic component, therefore the risk of autoimmune disease might be
      increased in family members of patients with SLE. However, there are currently no
      data that support a higher incidence of autoimmune disorders in the offspring of
      SLE patients. Babies with neonatal lupus are not at increased risk to develop SLE
      in later life, but a continued follow-up is suggested, especially prior to
      adolescence and if the mother herself has an autoimmune disease.

PMID- 15485115
TI  - Drug exposure in pregnant women.
AB  - The objectives of this paper are to describe the Hungarian case-control
      surveillance system of congenital abnormalities (HCCSCA), to summarize the
      principles of this activity and our main experiences. Among the main principles,
      the importance of the time factor (the first trimester concept is outdated), the
      differentiation of isolated and multiple manifestations of the seemingly same
      congenital abnormalities, noxa specificity, the separation of drugs and pregnancy
      supplements within medicinal products (or medicines) are stressed. After some
      methodological problems (recall bias, chance effect), the main experiences
      regarding the risk and benefit of medicines are summarized. The conclusion is
      that the results of our studies based on the data set of the HCCSCA showed that
      at present the exaggerated teratogenic risk of drugs is much more harmful for the
      fetus than the real teratogenic effect of some drugs themselves. Medical doctors
      and other experts therefore need more education to know the principles and
      findings of modern human teratology because it may help us to have a better
      balance between the risk and benefit of drug use during pregnancy.

PMID- 15485116
TI  - Disease specific problems related to drug therapy in pregnancy.
AB  - Rheumatic diseases occur frequently in women of childbearing years necessitating
      drug treatment also during a concurrent pregnancy in order to control maternal
      disease activity and to ensure a successful pregnancy outcome. This survey
      reviews maternal and fetal side effects of nonsteroidal anti-inflammatory drugs
      (NSAID) and immunosuppressive agents in pregnant patients. The classic
      nonselective nonsteroidal anti-inflammatory drugs are not teratogenic, but given
      in late pregnancy they can induce renal and cardiac side effects in the fetus.
      Similar effects must be expected of the new, selective Cox2-inhibitors. NSAID
      should therefore be stopped by gestational week 32. Corticosteroids are
      frequently necessary to control rheumatic disease flares and for prevention of
      serious organ manifestations. However, due to an increased risk of oral clefts,
      high doses (1-2 mg/kg) should be avoided in the first trimester. Among disease
      modifying drugs, sulfasalazine and antimalarials have the safest record.
      Cyclosporine and azathioprine can be given throughout pregnancy if disease
      control requires it. Insufficient data exist for treatment of pregnant patients
      with TNF-inhibitors and mycophenolate mofetil. The severity of the disease under
      treatment decides if continuation of one of these drugs is justified.
      Prophylactic withdrawal of drugs before pregnancy is mandatory for leflunomide
      and the cytotoxic agents methotrexate and cyclophosphamide. Prepregnancy
      counselling and careful monitoring during pregnancy help to tailor necessary drug
      treatment for the benefit of mother and child.

PMID- 15485117
TI  - Leadership for dentists.

PMID- 15485118
TI  - Management of dental patients on warfarin therapy in a primary care setting.
AB  - The surgical management of patients on anticoagulant therapy is often poorly
      understood in all fields of medicine (not just dentistry). Until now there has
      been no uniform approach to managing these patients and much of the advice
      routinely given by medical practitioners and haematologists has fallen behind the
      recent evidence. Many medical conditions from atrial fibrillation to prosthetic
      heart valves predispose patients to venous thrombosis and pulmonary embolism
      (Table 1). In order to prevent these complications, these patients are normally
      placed on an anticoagulant. By far the most common one in use is Warfarin, which
      is a derivative of 4 hydroxycoumarin.

PMID- 15485119
TI  - Digital imaging for the general dental practitioner: 3. Extra-oral imaging.
AB  - Images of patients, x-rays, study models, and general views of the practice and
      staff were often left to the more experienced photographer. Digital imaging has
      rendered the majority of photography possible for the General Dental
      Practitioner. Difficult lighting conditions were often a problem in the past, but
      these can largely be overcome with the facilities built into the latest digital
      technology.

PMID- 15485120
TI  - The Dycal try-in technique for Resin-bonded bridges.
AB  - The resin-bonded bridge (RBB) is a predictable technique that has a useful place
      in modern day dentistry. Practitioners' main concerns, regarding this technique,
      are a lower survival rate when compared with conventional prostheses, and
      unpredictable aesthetics. Unfortunately, the minimal preparation and adhesive
      concepts used with RBBs complicates provisional cementation. Ideally, the RBB
      should be assessed as if it were the definitively bonded prosthesis. It is
      possible to achieve a good final aesthetic result as the grey shine-through of
      the metal wing can be eliminated by the use of opaque resin cements such as
      Panavia 21 OP. Ideally, the restoration should be assessed with an identical
      opaque try-in paste but, unfortunately, such a proprietary paste is not
      available. This paper describes the use of Dycal as a try-in paste for
      provisionally cementing a resin-bonded bridge and the benefits this offers.

PMID- 15485121
TI  - Keeping your eye on the ball.
AB  - Dentigerous cysts develop from unerupted and impacted permanent teeth. Very
      rarely, supernumerary teeth are associated with dentigerous cysts and constitute
      about 5-6% of all dentigerous cysts. Although these cysts are not common in the
      first decade of life, regular thorough inspection of radiographs is of
      importance, as indicated by this case report. This case shows how an impacted
      supernumerary canine developed a dentigerous cyst, engulfing the whole of the
      maxillary antrum.

PMID- 15485122
TI  - Diffuse sclerosing osteomyelitis in the maxilla: case report.
AB  - A case of diffuse sclerosing osteomyelitis (DSO) in the maxilla of a 25-year-old
      male is presented. His chief complaint was recurrent painless swelling in the
      maxillary right molar region over a 3-year-period. The periapical and panoramic
      radiographs of the right maxilla showed diffuse sclerotic areas. Computed
      tomography (CT) indicated a high density area in the right maxilla. Although the
      tentative diagnosis was fibrous dysplasia on the basis of history, clinical
      symptoms and radiologic examination, the biopsy results supported chronic diffuse
      sclerosing osteomyelitis. The maxillary location and the painless course of the
      lesion in a male patient is a rare occurrence.

PMID- 15485123
TI  - The 'combination syndrome' revisited.
AB  - The 'combination syndrome' may present a considerable clinical and technical
      challenge to the dental practitioner. This clinical scenario classically relates
      to changes found in the mouth following use of a maxillary complete denture that
      has opposed natural mandibular anterior teeth. While this condition was first
      recognized over 30 years ago, the associated difficulties still pervade the
      practice of prosthetic dentistry today. The purpose of this article is to
      describe treatment of two patients who exhibited clinical features of this
      condition, and review some of the relevant literature on this condition.

PMID- 15485124
TI  - Oral piercing and associated complications: two case reports.
AB  - These two cases, which presented in a three-month period to a Maxillofacial
      Surgery Department of a District General Hospital, demonstrate problems that can
      occur following oral piercing.

PMID- 15485125
TI  - Research in a dental practice setting.
AB  - There is a shortage of research from dental practice. The aim of this article is
      to stimulate more interest in dental research. This is done by explaining the
      basic principles of doing research in a dental practice setting. Examples are
      taken from the author's own practice. Emphasis is placed on the following points:
      how to develop and research ideas; factors specific to dental practice; how
      articles and journals are rated; making a protocol for the study; examiners'
      reliability and statistical analysis.

PMID- 15485126
TI  - Cochlear activation at low sound intensities by a fluid pathway.
AB  - In order to assess the mechanisms responsible for cochlear activation at low
      sound intensities, a semi-circular canal was fenestrated in fat sand rats, and in
      other experiments a hole was made in the bone over the scala vestibuli of the
      first turn of the guinea-pig cochlea. Such holes, which expose the cochlear
      fluids to air, provide a sound pathway out of the cochlea which is of lower
      impedance than that through the round window. This should attenuate the pressure
      difference across the cochlear partition and thereby reduce the driving force for
      the base-to-apex traveling wave along the basilar membrane. The thresholds of the
      auditory nerve brainstem evoked responses (ABR) and of the cochlear microphonic
      potentials were not affected in the fenestration experiments. In addition, holes
      in the scala vestibuli of the first turn did not cause ABR threshold elevations.
      These results contribute further evidence that at low sound intensities the outer
      hair cells are probably not activated by a base-to-apex traveling wave along the
      basilar membrane. Instead it is possible that they are excited directly by the
      alternating condensation/rarefaction fluid pressures induced by the vibrations of
      the stapes footplate. The activated outer hair cells would then cause the
      localized basilar membrane movement.

PMID- 15485127
TI  - Frequency discrimination training: is there ear symmetry?
AB  - While it is well documented that significant improvements in a frequency
      discrimination task occur following training of normal-hearing adult subjects,
      less is known about the symmetry between the ears. The objectives of the present
      study were (1) to compare the first obtained DLF thresholds between left and
      right ears, (2) to determine whether single-session training would result in
      similar improvements in those subjects trained in the right ear versus those
      trained in the left ear, and (3) to evaluate the generalization of learning to
      the untrained ear and compare its extent between the left and right ears. Two
      groups of 10 normal-hearing subjects participated in a single-session training.
      One group of 10 subjects was trained in the left ear and the second group of 10
      additional subjects was trained in the right ear. Single-session training
      consisted of 10 difference limen frequency (DLF) thresholds for 1 kHz using a two
      interval, two-alternative forced choice paradigm. Generalization to the untrained
      ear was tested 24 hours post-training. Our results show that: (1) No significant
      differences were found in the first obtained DLF thresholds between left and
      right ears; (2) Similar improvement in DLF thresholds occurred in both ears for
      single-session training; and (3) Twenty-four hours post-training, learning
      generalized to the untrained ear with similar generalization to both ears. Future
      studies are required in order to establish whether this symmetry is maintained
      with verbal stimuli and/or after multi-session training.

PMID- 15485128
TI  - Frequency discrimination thresholds: the effect of increment versus decrement
      detection of frequency.
AB  - Difference limen for frequency (DLF) is traditionally tested using a frequency
      increment detection paradigm in which listeners are requested to distinguish
      between a reference tone and a series of comparison tones of higher frequency.
      Sporadic findings indicated that an increment paradigm is not necessarily
      comparable to a decrement paradigm, in which the comparison tones are lower than
      the reference tone. The purpose of the present study was to test whether the
      ability to detect frequency increments is different from that of frequency
      decrements. DLFs of 16 young women were measured at 200 Hz and 1,000 Hz, using
      detection of both frequency increment and decrement paradigms. Results indicated
      that: (1) the frequency increment detection paradigm was significantly smaller
      (i.e., superior) to the decrement paradigm for the DLF task at 200 Hz, (2) for
      both frequencies, the number of participants who exhibited better DLF using the
      frequency increment detection paradigm was significantly larger than the number
      of those who had better DLFs using the frequency decrement paradigm, and (3) for
      both frequencies, strong correlations were found between DLFs obtained in the
      increment versus the decrement paradigms. These results have implications: (1) to
      studies whose subjects may have reduced sensitivities at frequencies higher than
      the reference tone (such as the hearing impaired), and (2) to models related to
      the role of auditory feedback on voice accuracy and to the underlying processes
      of frequency discrimination.

PMID- 15485129
TI  - Are the perceptual effects of spectral smearing influenced by speaker gender?
AB  - The purpose of this study was to determine whether the effect of loss of spectral
      detail on speech perception is influenced by the gender of the speaker. Spectral
      smearing was carried out by multiplying the speech signal by a series of low
      passed white noise samples, causing tonal components in the signal to be replaced
      by noise. Smearing bandwidths of 0 Hz (no smearing), 250 Hz, 500 Hz, 1,000 Hz,
      2,000 Hz, 4,000 Hz, 8,000 Hz and full bandwidth were used. Smearing was applied
      to 15 isophonemic lists, each with 10 one-syllable CVC Hebrew words. The words
      were recorded using two speakers, a male and a female, both native speakers of
      Hebrew. A total of 23 subjects participated in the study: eight listened to the
      male speaker and 15 to the female. The results show no significant differences in
      the effect of speaker on recognition of words, phonemes, vowels and consonants at
      the different smearing bandwidths. The results also show that regardless of the
      speaker's gender, vowels were adversely affected by spectral smearing, as
      compared to consonants. Interpolation of the results shows that smearing
      bandwidths of 1,080 Hz, 1,950 Hz, 1,590 Hz and 2,150 Hz are required to reduce
      word, phoneme, vowel and consonant recognition to 50%, respectively. Several
      tentative explanations are offered for the fact that the results were independent
      of gender: all smearing bandwidths were larger than the average interharmonic
      spacing for both speakers, and the difference between male and female formant
      frequencies is typically smaller then the difference in formant frequencies of
      the different vowels.

PMID- 15485130
TI  - NRT-based versus behavioral-based MAP: a comparison of parameters and speech
      perception in young children.
AB  - The present study was designed to evaluate the effect of neural response
      telemetry (NRT)-based cochlear implant (CI) programming versus behavioral-based
      programming on electrical stimulation parameters (MAP) threshold (T) and
      comfortable (C) levels and speech perception abilities in young children, during
      the first year of implant use. Ten congenitally deaf children at the age of 12-39
      months (mean age: 25.2 months) implanted with the Nucleus 24R(CS) CI participated
      in the study. The group was randomly divided into two: (1) NRT-based MAP group (n
      = 5) consisted of children who were programmed using intra-operative NRT
      measurements; (2) behavioral-based MAP group (n = 5) consisted of children who
      were programmed using the behavioral responses of the patients. MAP parameters as
      well as sound-field aided thresholds and speech perception abilities were
      compared between the two groups at consecutive programming sessions: 1, 3, 6, and
      12 months post initial stimulation. Results indicated no significant differences
      among NRT-based MAPs and behavioral-based MAPs. Although MAP profiles at initial
      stimulation differed in the apical region, these differences decreased with time.
      In addition, a gradual increase of T and C levels of NRT-based MAPs as well as
      those of behavioral-based MAPs was evident until the 1-month time point,
      thereafter stabilization occurred. Sound-field aided thresholds improved with
      time for both groups; however, they were found to be significantly better for the
      NRT-based MAP group. Despite these differences, speech perception abilities were
      comparable among groups at 12 months post initial stimulation. NRT-based
      programming was found to be significantly shorter than behavioral-based
      programming. In conclusion, for this small group of children, our findings
      support the use of NRT for programming of young children during the initial
      period after implantation.

PMID- 15485131
TI  - The contribution of the time locking of EEG waves to the generation of the
      auditory P300.
AB  - OBJECTIVES: To study the time locking of the 'natural' (delta, theta, slow alpha,
      fast alpha and beta) EEG waves during the generation of the P300 in passive
      (P300a) and active (P300b) auditory oddball paradigms in order to obtain insights
      into the generation of the P300 and into the transitions between background and
      evoked activity. METHODS: Tone burst stimuli (standard and deviant) were
      delivered to normal young adult subjects in passive and active oddball paradigms.
      The time distributions of EEG waves were analyzed in several frequency bands
      during background and post-stimulus periods. RESULTS: The ongoing background
      activity was modified by the deviant stimulus, producing the time locking of the
      positive delta, theta and alpha EEG deflections in the time range of the P300.
      This involved prolongation of the positive component of negative-positive wave
      complexes so that the positive wave was delayed into the time period of the P300.
      The time locking effects were more prominent in the delta and theta ranges, and
      differed in frequency components and scalp topography between the two paradigms.
      Not all deviant stimulus trials contributed deflections to the P300. The
      contributing trials can be selected, providing the basis for single trial
      analysis. CONCLUSIONS: The study of the time locking of the EEG waves in
      different frequency bands provides improved analysis of the P300 and an approach
      to single deviant stimulus trial analysis, that in turn can enhance signal-to
      noise ratios. The results show that the time reorganization of EEG can be
      considered in the generation of P300 separately from the amplitude factor.
      SIGNIFICANCE: This can lead to improved analysis of normal and abnormal brain
      function in individual subjects.

PMID- 15485132
TI  - Role of genetic factors in the etiopathogenesis of cerebrovascular accidents:
      from an animal model to the human disease.
AB  - 1. The present work summarizes current knowledge on the genetic susceptibility to
      stroke, a complex cardiovascular phenotypic trait due to both gene/environment
      and gene/ gene interactions. 2. Evidence for the existence of genes directly
      contributing to stroke occurrence was first obtained in the animal model of the
      stroke-prone (sp) spontaneously hypertensive rat (SHR) through a linkage analysis
      approach in F2 segregating hybrid populations. In fact, several Quantitative
      Trait Loci (QTLs) were detected in different chromosomes of the rat. Candidate
      genes were identified (ANP, BNP, Adrenomedullin) and subsequently analyzed to
      obtain information on the fine disease mechanisms possibly dependent from
      specific sequence mutations. 3. The most important achievement was represented by
      the fact that the gene encoding ANP appeared to play a role in the disease of
      both rats and humans, thus providing a suggestive parallelism between the animal
      model and the human cerebrovascular disease. A more extensive analysis is
      required to identify the potential pathogenic role of genetic factors involved in
      human stroke.

PMID- 15485133
TI  - Substrain differences, gender, and age of spontaneously hypertensive rats
      critically determine infarct size produced by distal middle cerebral artery
      occlusion.
AB  - 1. The present work discussed the effects of substrain or genetic differences,
      gender, and age of the rat on infarct size produced by distal middle cerebral
      artery occlusion (MCAO) in spontaneously hypertensive rats (SHR). 2. In
      SHR/Kyushu, infarct volume was significantly larger than that of SHR/Izm, while
      blood pressure levels were essentially the same between the two substrains.
      Although SHR-SP/Izm had a higher blood pressure than SHR/Kyushu, infarct volumes
      were the same between SHR/Kyushu and SHR-SP/Izm. These results suggest the
      presence of blood pressure-independent factors which affect the infarct size
      after MCAO. 3. Estrogen accounted the large part of greater tolerability against
      focal brain ischemic injury in female compared with male SHR. 4. We found age
      related vulnerability to focal cerebral ischemia in female SHR. This age-related
      vulnerability in aged female SHR was unrelated to the blood levels of sex
      hormones such as estrogens and progesterone. 5. Finally, we emphasized the
      importance of reproducible and least invasive focal ischemia models in stroke
      research.

PMID- 15485135
TI  - The stroke-prone spontaneously hypertensive rat: how good is it as a model for
      cerebrovascular diseases?
AB  - 1. Cerebrovascular diseases (CVDs) in humans are a mixture of diseases with
      different etiologies. 2. Although the stroke-prone spontaneously hypertensive rat
      (SHRSP) cannot represent all types of CVDs, it is probably a good genetic model
      for particular types such as lacunar infarction and intracerebral hemorrhage. 3.
      Genetic studies suggested that SHRSP has genetic susceptibility to stroke
      independent of its severe hypertension. Studies on SHRSP may provide useful
      information with which to dissect genetic susceptibility to particular types of
      CVDs.

PMID- 15485134
TI  - Nutritional prevention on hypertension, cerebral hemodynamics and thrombosis in
      stroke-prone spontaneously hypertensive rats.
AB  - 1. Stroke-prone spontaneously hypertensive rats (SHRSP/Izm), which become
      severely hypertensive and exhibit a very high incidence of stroke (cerebral
      hemorrhage and/or infarction), are used widely for the study of the hypertension
      and stroke. In the previous study, we indicated that high thrombotic tendency of
      cerebral microvessels in SHRSP/Izm compared with stroke-resistant SHR (SHR/Izm)
      and normotensive Wistar Kyoto rats (WKY/Izm) at aged period. 2. L-arginine, a
      substrate of nitric oxide (NO), and voluntary exercise reduced blood pressure and
      thrombotic tendency in cerebral microvessels caused by highly production of NO in
      vivo. Furthermore, antioxidants show that the effects of antihypertensive and
      antithrombosis in SHRSP/Izm. 3. Although SHRSP/Izm become genetically
      hypertensive and exhibit stroke, a number of nutritional factors, particularly
      antioxydative nutrient, have preventive effects on hypertension, cerebral blood
      flow dysfunction, thrombus formation, and neuronal cell death in SHRSP/Izm. Our
      results indicate that those treatments are beneficial in the prevention of
      hypertension and stroke and that the nutritional science is very important for
      "prediction and prevention medicine."

PMID- 15485136
TI  - Properties of connexin26 hemichannels expressed in Xenopus oocytes.
AB  - 1. Hemichannels formed by connexin26 (Cx26) on the horizontal cell dendrites that
      invaginate cone terminals in the vertebrate retina have been implicated in the
      feedback mechanism by which horizontal cells regulate transmitter release from
      cone photoreceptors. However, their membrane properties had not been studied
      previously, and it was unclear whether they could subserve their purported
      function at the membrane potentials over which horizontal cells operate. 2. We
      used the two-electrode voltage clamp technique to record the membrane currents
      and pharmacological properties of Cx26 hemichannels formed in the Xenopus oocyte
      expression system. 3. Oocytes expressing Cx26 exhibited large membrane
      conductances over a broad range of hyperpolarizing and depolarizing membrane
      potentials, and displayed little evidence of voltage-dependent gating, indicating
      that the hemichannels are constitutively open. The Cx26-mediated nonjunctional
      currents were relatively insensitive to quinine, a cinchona alkaloid that opens
      hemichannels formed by several other connexins. However, the hemichannel currents
      were blocked by carbenoxolone, a rise in extracellular calcium, or lowering
      intracellular pH. The currents could also be suppressed by reducing extracellular
      pH, and by the chloride channel blocker NPPB through its direct interaction with
      Cx26 hemichannels. 4. These findings provide a basis with which to evaluate the
      in situ pharmacological studies that attempt to assess the putative role of Cx26
      hemichannels in the feedback pathway in the distal retina.

PMID- 15485137
TI  - Distribution of neuropeptide Y-immunoreactive neurons in the human brainstem,
      cerebellum, and cortex during development.
AB  - 1. Neuropeptide Y is found throughout the central nervous system where it appears
      to play a wide range of often poorly understood functions. In this study, the
      distribution of neuropeptide Y immunoreactive (NPY-ir) neurons in the brainstem,
      cerebellum, and cerebral cortex of human fetuses ranging in age from 11
      gestational weeks to term was investigated by immunohistochemistry. 2. The NPY-ir
      cells were detected in the dorsal and ventral rostral midbrain and the
      interpeduncular nucleus by 21 weeks and 32 weeks of gestation, respectively.
      Although no positive cells were found in the pons, the NPY-ir fibers were
      detected there at 32 gestational weeks. 3. The vagal, hypoglossal, and olivary
      nuclei of the medulla oblongata contained immunoreactive cells by week 21 and the
      medullary reticular formation by week 25 of gestation. In most of these
      locations, both the number and size of neuropeptide Y positive cells were greater
      at birth and reached maximal values of 100-400 cells per 1 mm2 and 2-5 microm in
      diameter, respectively. 4. In the cerebellum, numerous NPY-ir horizontal and
      granule cells, as well as the cells within the dentate nucleus were observed as
      early as 21 weeks of gestation. 5. The NPY-ir cells were also detected in the
      developing cerebral cortex, with the earliest activity observed within the
      temporal cortex at 14 weeks of gestation. By week 21, positive cells appeared in
      the visual, frontal, sensory, and motor cortices. Most of these cells were
      bipolar or multipolar in morphology but their numbers at birth were relatively
      low. 6. Our results show a wide distribution of the NPY-ir cells in the
      developing human brain and offer supporting evidence for the important modulatory
      role of NPY in both the fetus and adult.

PMID- 15485138
TI  - Hypoxic excitability changes and sodium currents in hippocampus CA1 neurons.
AB  - 1. The objective of the present study was to distinguish if inhibition of
      neuronal activity by hypoxia is related to a block of voltage-gated Na+ channels.
      2. The effect of chemical hypoxia induced by cyanide (0.5 mM, 10 min perfusion)
      was studied with patch-clamp technique in visualized intact CA1 pyramidal neurons
      in rat brain slices. Action potentials were elicited in whole cell current-clamp
      recordings and the threshold was estimated by current pulses of 50-ms duration
      and incremental amplitudes (n = 31). The effect of cyanide on the Na+ current and
      conductance was studied in voltage clamp recordings from cell-attached patches (n
      = 13). 3. Cyanide perfusion during 10 min increased the threshold for excitation
      by 73 +/- 79 pA (p = 0.001), which differed from the effect in control cells (11
      +/- 41 pA, ns). The change in current threshold was correlated to a change in
      membrane potential (r = -0.88, p < 0.0001). Cyanide had no significant effect on
      the peak amplitude, duration, or rate of rise of the action potential. 4. Cyanide
      perfusion did not change the Na+ current size, but caused a small decrease in ENa
      (-17 +/- 22 mV, ns) and a slight increase in Na+ conductance (+14 +/- 26%, ns),
      which differed (p = 0.045) from controls (-19 +/- 23 %, ns). 5. In conclusion,
      chemical hypoxia does not cause a decrease in Na+ conductance. The decreased
      excitability during hypoxia can be explained by an increase in the current
      threshold, which is correlated with the effect on the membrane potential.

PMID- 15485140
TI  - Do new mental health plans put patients first?

PMID- 15485139
TI  - Tacrolimus-induced neurotoxicity and nephrotoxicity is ameliorated by
      administration in the dark phase in rats.
AB  - 1. Tacrolimus, a potent immunosuppressant, induces impaired renal function and
      neurological complications. We investigated the influence of dosing time on the
      neurotoxicity, nephrotoxicity, and immunosuppressive effect of tacrolimus in
      rats. 2. The repeated injection of tacrolimus in the light phase (8:00) produced
      a significantly greater increase than that in the dark phase (20:00) in the
      duration of harmine-induced tremors and in the blood urea nitrogen (BUN)
      concentration in rats. An immunosuppressive effect of tacrolimus on the
      xenotransplantation of mouse-to-rat skin grafts was apparent in the dark phase
      but not in the light phase. 3. The dosing time-dependent pharmacokinetic results
      were not observed when tacrolimus concentrations in rat whole blood were measured
      after a single or repeated injection in the light or dark phase. 4. These
      findings suggest that treatment in the active phase of the diurnal cycle
      ameliorates neurotoxicity and nephrotoxicity while maintaining the
      immunosuppressive effect of tacrolimus. The present findings have important
      implications for therapeutic approaches to avoid tacrolimus-induced neurotoxicity
      and nephrotoxicity.

PMID- 15485141
TI  - Is intuition as valid as evidence-based practice? Yes.

PMID- 15485142
TI  - Is intuition as valid as evidence-based practice? No.

PMID- 15485143
TI  - Updating practice in pressure area care.

PMID- 15485144
TI  - Exchanging expertise in COPD care.

PMID- 15485145
TI  - Why is verbal abuse getting worse?

PMID- 15485146
TI  - Making nurse-led discharge work to improve patient care.
AB  - This article discusses nurse-led discharge and provides guidance. Robust
      implementation of nurse-led discharge requires a thorough understanding of the
      'discharge planning' process, and also requires educational support, training and
      achievement of discharge competencies. Without these, nurse-led discharges are at
      risk of becoming yet another quick-fix remedy for freeing up hospital beds.

PMID- 15485147
TI  - What you need to know about amenorrhoea.

PMID- 15485148
TI  - Understanding the importance of effective diabetes management.

PMID- 15485149
TI  - Understanding the role of exercise in health promotion.
AB  - An inactive lifestyle is associated with poor health. Exercise is an important
      part of preventative strategies for many chronic conditions. This guided
      reflection article examines evidence on the role of exercise in preventing weight
      gain, osteoporosis, diabetes, cardiovascular disease and mental health problems.
      It aims to enable nurses to make informed recommendations to their patients about
      the ways in which appropriate exercise can bring health-related benefits.

PMID- 15485150
TI  - Setting up a project to improve care of older people in Scotland.
AB  - This is the first of two articles which describe the 'Developing as a centre of
      excellence project' at the School of Health, Nursing and Midwifery at the
      University of Paisley. The aim of the project was to enhance good gerontological
      care by creating a partnership between clinicians and academic staff.

PMID- 15485151
TI  - Implications of and treatment options for retinal detachment.
AB  - The retina is a complex structure that turns light falling onto it via a chemical
      reaction into nerve impulses, which then travel to the brain for interpretation
      into images. If the retina is damaged or moved from its correct location, a
      person's ability to interpret the world is compromised with all the physical,
      social and psychological effects this implies. Nurses have a key role in the
      recognition of signs and symptoms of retinal compromise as well as the care and
      treatment of patients who undergo therapy for retinal detachment, so that the
      best possible vision is achieved for each patient.

PMID- 15485152
TI  - Making your job application stand out.

PMID- 15485153
TI  - Who put the US in charge of global morality?

PMID- 15485154
TI  - [Early diagnosis and surgical management of prostate cancer].
AB  - Prostate cancer is a significant cause of morbidity and mortality in the United
      States and Europe. The natural ageing of the population as well as the continued
      and widespread use of diagnostic tests such as prostate specific antigen (PSA),
      has led to an increase in the numbers of men diagnosed with localised prostate
      cancer. Screening to identify organ-confined disease has provoked much public and
      scientific attention, but remains controversial. Radical prostatectomy is one of
      the most challenging urological procedures performed. Improvements in technique
      due to better understanding of pelvic anatomy have reduced complications, with
      acceptable standards and excellent results in high-volume institutions. Continual
      refinements in technique and the recent introduction of laparoscopic radical
      prostatectomy are likely to improve functional outcome further. However the
      effectiveness of surgery in improving survival and quality of life, in men with
      early prostate cancer remains to be determined. The results from large randomised
      controlled trials are eagerly awaited.

PMID- 15485155
TI  - [Adrenocortical secretory tumors].
AB  - Adrenocortical tumors are rare and mostly non-secreting; their discovery is
      incidental. When secreting, they produce steroid excess and result in a clinical
      presentation such as the Cushing syndrome, primary aldosteronism, virilization or
      feminization syndrome. Such tumors are mostly sporadic but can belong to
      hereditary syndromes predisposing to tumors. The diagnosis of secreting
      adrenocortical tumors is based upon clinical presentation and biological data
      associated with specific biological assessments. Adrenal imaging has been
      considerably improved with the development of CT scan, which can be completed by
      MRI if necessary. Most of adrenocortical tumors are adenoma, nevertheless some of
      them can be malignant and the prognosis of such carcinomas is poor. Management of
      secreting adrenocortical tumors requires surgery in most of the cases and
      laparoscopic access is now widely used and provides good results in the treatment
      of benign tumors.

PMID- 15485157
TI  - [Treatment of adult hydrocele].
AB  - Surgery is the gold standard of hydrocele treatment; it is indicated in case of
      functional disorders. The two principal techniques are Lord's plication
      procedure, and excision. Main complications consist in potential haematoma and
      injury to epididymis, vas deferens or cord structures. Two other techniques
      exist, but with limited indications: fenestration which puts in contact the sac
      with lymph-rich subcutaneous tissues, and sclerotherapy.

PMID- 15485156
TI  - [Fetal renal impairment syndrome].
AB  - Some anomalies of the kidney and urinary tract evolving in utero may compromise
      the renal function in the newborn. Early therapeutic options do exist, especially
      in obstructive nephropathies. The decision depends on a correct evaluation of the
      foetal enal function and prognosis, which is based on a range of methods:
      ultrasound echography, biochemical analysis of foetal urine, and, more recently,
      foetal serum markers such a beta-2 micro globulin. These methods are reviewed.

PMID- 15485158
TI  - Preparation or excessive reduction.

PMID- 15485159
TI  - Computerized image capture, storage, retrieval, and enhancement in digital
      radiography.

PMID- 15485160
TI  - Restoring tetracycline-stained teeth with a conservative preparation for
      porcelain veneers: case presentation.
AB  - Tetracycline exposure in utero and in early childhood often results in intrinsic
      tooth staining that varies in severity based upon timing, duration, and form of
      tetracycline administered. Traditionally, dental aesthetics compromised by
      tetracycline staining have been restored with modalities requiring aggressive
      tooth preparation. In this case involving a patient with extremely severe
      staining of healthy and aesthetically shaped dentition, a conservative tooth
      preparation strategy and porcelain veneers were utilized to preserve tooth shape
      and arch form while restoring natural color.

PMID- 15485161
TI  - Controlled light polymerization: does it work?

PMID- 15485162
TI  - Achieving optimal aesthetics using contemporary porcelain materials: a case
      report.
AB  - While the selection of an appropriate material contributes to restorative
      success, a thorough treatment plan with enhanced clinician/technician
      communication is required to ensure an appropriate and aesthetic result. A
      concise understanding of the patient's existing condition, desires, and
      expectations is critical to ensure restorative success. This case presentation
      demonstrates the clinical and laboratory protocols for the development of
      predictable, functional, and aesthetic porcelain restorations in treating
      severely compromised maxillary anterior dentition.

PMID- 15485163
TI  - The use of two porcelain materials in the development of optimal aesthetics: the
      role of shade matching on restorative success.

PMID- 15485164
TI  - Detecting and diagnosing caries: past to present.

PMID- 15485165
TI  - Biologically driven prosthetic options in implant dentistry.

PMID- 15485166
TI  - Diabetes mellitus: a clinical update of terminology, prevalence, and economics.

PMID- 15485167
TI  - Current trends in implantology: Part 1--Biological response, implant stability,
      and implant design.
AB  - In implant dentistry, the loss of bone is generally caused by infection or trauma
      but can also be attributed to other involved factors. Innovative surgical
      techniques and implant components have been developed in an effort to overcome
      the challenges (eg, bone topography and density, primary and secondary stability,
      aesthetics) traditionally associated with implant-supported restorations.

PMID- 15485168
TI  - [When should liver biopsy be considered? Slightly increased ALAT can indicate
      steatosis--but a histological test is necessary for prognosis].

PMID- 15485169
TI  - [Cochlear implantation in children should be bilateral and preferably performed
      before the age of 1 year].

PMID- 15485170
TI  - [Intestinal transplantation--an experimental therapy which has become a realistic
      alternative].
AB  - Outcome after intestinal transplantation has improved dramatically since the
      introduction of novel immunosuppressive agents and refined surgical techniques.
      Small bowel transplantation is now considered to be the best treatment modality
      for patients with life threatening complications of intestinal failure and
      parenteral nutrition. We hereby review the international experience as well as
      the first ten cases of intestinal transplantation performed in Sweden.

PMID- 15485171
TI  - [A case report of systemic capillary leak syndrome. Effective treatment with
      immunoadsorption and leukotriene antagonist].
AB  - Systemic capillary leak syndrome (SCLS) is an unusual condition characterized by
      periodic leakage of plasma proteins through the capillary wall, leading to
      hypoalbuminaemia, hypovolaemia, haemoconcentration and shock. The pathogenesis is
      unknown and the mortality high. Various prophylactic treatments have been tried
      but are difficult to evaluate because of the unpredictable course of the disease.
      We describe one patient with frequent attacks of SCLS, that did not respond to
      any kind of treatment regimens over a period of nine years. Subsequently, therapy
      with regular immunoadsorption of plasma proteins and a leukotriene receptor
      antagonist was attempted. This treatment has now been given for six years and
      only one episode of capillary leakage has occurred. The effect may be due to
      removal of pathogenic immunoglobulins or immune complexes and/or inhibition of
      leukotriene-induced capillary leakage.

PMID- 15485173
TI  - [Weather change--a cause of myocardial infarction. Barometric pressure over the
      Arctic region affects the number of sudden cardiac death cases].
AB  - Previous studies have reached different conclusions as to whether geomagnetic
      activity, or weather and weather changes are related to the risk of having or
      dying from an acute myocardial infarction (AMI). We linked the Northern Sweden
      MONICA AMI registry to databases on temperature, barometric pressure, relative
      humidity, the Arctic Oscillation (AO), and geomagnetic activity and found that a
      temperature rise increased the number of non-fatal AMIs, an increase in the AO
      increased fatal as well as non-fatal AMIs, but there was no relation between the
      geomagnetic activity and AMI incidence or case fatality.

PMID- 15485172
TI  - [New reference interval for ALAT does not identify subclinical liver disease.
      Lower limit than the proposed should be used for medical considerations!].
AB  - Recently a new reference interval for serum ALT, based on samples from up to 3000
      healthy adult reference persons, was proposed. In the present study we performed
      a retrospective analysis of biochemical and histological data from 178
      asymptomatic patients currently considered to have increased ALT. Forty-five
      patients (25%) had serum ALT levels within the new proposed reference interval.
      Of those, only one had normal liver histology. Of the remaining 44 patients with
      abnormal liver histology, 34 exhibited fatty infiltration. It is concluded that
      if the new proposed reference interval for serum ALT is used as "healthy" ranges,
      the sensitivity of this test in identifying subclinical liver disease will be
      decreased.

PMID- 15485174
TI  - [Current plastic surgery in abnormalities of female genitalia].

PMID- 15485175
TI  - [Vulvovaginal surgery for esthetic and functional problems. Satisfied patients
      according to a questionnaire from a private clinic].

PMID- 15485176
TI  - [Health care in the USA depends more and more on drug industry].

PMID- 15485177
TI  - "The dental cripple": a new approach to severe mandibular atrophy.
AB  - We have found this use of the composite graft of the severely atrophic mandible
      to offer a very predictable successful technique for the "severe dental cripple".
      It is only with the advent of the osseointegrated implants that this technique
      really can be fully utilized. The inferior border grafting certainly addresses
      the issue of pathologic fracture, but without the use of implants, it would not
      enhance the prosthetic environment intraorally. By combining these grafting and
      implant techniques, we feel that this is not only a predictable surgical
      technique, but it also offers the advantages of less resorption, cleaner surgical
      incisions, and less interruption of prosthesis use during the healing phases
      (Figs. 7 & 8). We are continuing to follow the initial group of patients who have
      undergone this therapy, and the lack of resorption to date has been extremely
      encouraging.

PMID- 15485179
TI  - A century celebration: Harold D. Bowman, D.D.S.

PMID- 15485178
TI  - Long term analysis of conservative therapy for TMJ dysfunction: a patient
      evaluation.

PMID- 15485180
TI  - Beyond the classroom.

PMID- 15485181
TI  - An overview of implant imaging.

PMID- 15485182
TI  - The Fiji School of Medicine: a volunteer's experience.

PMID- 15485184
TI  - Dentistry: changing with the ages.

PMID- 15485183
TI  - The role of iron in periodontal disease.

PMID- 15485185
TI  - Dentistry hits the road.

PMID- 15485186
TI  - Gastroscopy (a preliminary communication). 1969.

PMID- 15485187
TI  - Fibergastroscopy--a report of 122 examinations. 1973.

PMID- 15485188
TI  - A review of rectal biopsies. 1974.

PMID- 15485189
TI  - Hepatitis B antigen in blood donors in Karachi. 1974.

PMID- 15485190
TI  - Plasma vitamin 'A' levels in hepatitis and cirrhosis. 1974.

PMID- 15485191
TI  - Liver disease in hepatitis B antigen (HBAg) positive blood donors. 1976.

PMID- 15485192
TI  - Clinical and biochemical study of 114 cases of cholelithiasis. 1976.

PMID- 15485193
TI  - Gall-stone composition and biochemical alterations in the serum of patients with
      cholelithiasis. 1976.

PMID- 15485194
TI  - Aflatoxin and liver cancer in Karachi--a preliminary survey. 1977.

PMID- 15485195
TI  - Hepatitis and hepatitis B surface antigen in health-care personnel. 1977.

PMID- 15485196
TI  - A study of the bacteriological pattern in gall bladder disease. 1986.

PMID- 15485197
TI  - Serum aspartate amino transferase and alanine amino transferase levels in
      apparently healthy population in Karachi. 1988.

PMID- 15485198
TI  - Immunogenicity of yeast-derived hepatitis B vaccine in Pakistani adults. 1990.

PMID- 15485199
TI  - Helicobacter pylori clearance and eradication with triple therapy in duodenal
      ulcer patients. 1995.

PMID- 15485200
TI  - Goodbye to the binge: the recovery house.

PMID- 15485201
TI  - Bill Clinton's big test: when he felt chest pains, he finally got an angiogram.
      Should you get one too?

PMID- 15485202
TI  - Advice from a bypass buddy: a heart-surgery veteran offers Bill Clinton a sneak
      preview of his new life.

PMID- 15485203
TI  - [CME-Radiology 1/Analysis. Dyspnea].

PMID- 15485204
TI  - [Assalix convinces in the daily practice in over 4700 patients. Long-term
      effective and tolerable in back and joint aches].

PMID- 15485205
TI  - [Does a reduction of drugs yield a higher quality of life in geriatric
      patients?].
AB  - Considering the constant increase of medication costs in medical institutions we
      analysed in a Swiss municipal nursing home whether medication in geriatric long
      term patients can be reduced without compromising quality of life. To document
      these effects we applied two established questionnaires on different issues of
      quality of life; the interviews with the patients and with the nursing staff were
      performed as a pre-post-comparison of the 3-month intervention. The new geriatric
      medication concept allowed a decreased daily medication as well as a 23%
      reduction of the medication costs at an average. In comparison to a previous
      group of control this study showed no reduction in quality of life for nursing
      home residents but even a stabilisation yielding to an actual improvement of
      quality of life.

PMID- 15485206
TI  - [Drug therapy knowledge in ambulatory cardiovascular patients].
AB  - To analyse drug therapy knowledge of prescribed drugs and self-administered
      medicinal products we interviewed 222 ambulatory cardiovascular patients.
      Spontaneous mentions of drugs (at least 3 preparations on average) were completed
      later on specific questioning. 40% of patients once interrupted their therapy due
      to adverse drug reactions. Most patients knew the labels of their medicaments but
      the effects and indications only in 50%. Nevertheless 70% were satisfied with the
      informations of the physician. Drugs available over the counter were consumed in
      many of the respondents: 50% consumed analgetics, and--mainly female patients-
      25% sedatives and 15% laxatives or diuretics. We conclude that specific
      questioning on self-administation of OTC preparations or formerly prescribed
      drugs results in an improved overview of medication and a better handling of
      polymedication and drug compliance.

PMID- 15485208
TI  - [Can falls in nursing homes be avoided?].
AB  - Fall-related injuries in nursing homes for the aged are frequent and cost
      intensive. Their iatrogenic causes are well known and avoided in modern geriatric
      institutions. We examined all falls in an institution during the period of 19
      months. Patients who carry out daily tasks on a semi-independent level were most
      at risk. The main risk-factor was dementia. Medication did not prove a major risk
      factor. At 37% p. a. the risk of falling was lower than in previous studies. This
      was due to a restriction on benzodiazepines with short term effects, minimising
      of neuroleptics, diuretics and other types of antihypertensives as well as
      avoidance of polypharmacy. Unavoidable risks need to be identified and should
      result in use of a hip protector.

PMID- 15485209
TI  - [Cost analysis for ambulatory patients in internal medicine].
AB  - We analyzed the diagnostical and therapeutical costs of 300 ambulatory patients
      over a two year period in a Swiss university policlinic of internal medicine. The
      calculations were based on the catalogue of hospital services
      (Spitalleistungskatalog) and the drugstore prices for pharmaceuticals
      (Apothekenpreise). The overall costs for the 300 patients were about 238,400 CHF.
      The refund by the health insurances represented 56% (excluding specific services
      such as radiological examinations). The main costs concerned analytical
      laboratory services (32%), physicians services (27%), technical services (26%),
      and pharmaceuticals (15%). Some analytical and technical services were prescribed
      unexpectedly frequently. Prevalent among the emitted pharmaceuticals were protone
      pump inhibitors, modern cardiovascular drugs and statins. Presumed reasons may be
      a minor cost awareness of the physicians and a trend towards modern but expensive
      therapies. An adequate cost awareness can only emerge from precise data of
      effective costs.

PMID- 15485210
TI  - [Acupuncture: great need of research].

PMID- 15485211
TI  - On the influence of the water electrostatic field on the amide group vibrational
      frequencies.
AB  - For clusters of N-methylacetamide and water molecules the performance of the
      fixed-charged approximation was tested against continuum and explicit ab initio
      models. The dispersion of the vibrational frequencies when constant electrostatic
      potential was maintained at the solute atoms was compared to the distribution
      caused by geometry fluctuations.

PMID- 15485212
TI  - Bound state spectroscopy of NH-He.
AB  - The NH-He van der Waals complex was characterized via laser excitation of bands
      associated with the NH A (3)Pi-X (3)Sigma(-) transition. It was demonstrated that
      the ground state supports a bound level with a rotational constant of B"=0.334(2)
      cm(-1). These results are in agreement with the predictions of recent high-level
      theoretical calculations. Spin-orbit predissociation of the excited complex was
      observed, and the spectra yield insights regarding the NH(A)+He potential energy
      surfaces.

PMID- 15485213
TI  - Coexistence of two different anion states in polyacene nanocluster anions.
AB  - Two types of anion states are shown to coexist in nanometer-scale polyacene
      cluster anions. Naphthalene and anthracene nanoclusters having a single excess
      electron were produced in the gas-phase. Photoelectron spectra of size-selected
      cluster anions containing 2 to 100 molecules revealed that rigid "crystal-like"
      cluster anions emerge, greater than approximately 2 nanometers in size, and
      coexist with the "disordered" cluster anion in which the surrounding neutral
      molecules are reorganizing around the charge core. These two anion states appear
      to be correlated to negative polaronic states formed in the corresponding
      crystals.

PMID- 15485214
TI  - Optimal linearized Poisson-Boltzmann theory applied to the simulation of flexible
      polyelectrolytes in solution.
AB  - Optimal linearized Poisson-Boltzmann (OLPB) theory is applied to the simulation
      of flexible polyelectrolytes in solution. As previously demonstrated in the
      contexts of the cell model [H. H. von Grunberg, R. van Roij, and G. Klein,
      Europhys. Lett. 55, 580 (2001)] and a particle-based model [B. Beresfordsmith, D.
      Y. C. Chan, and D. J. Mitchell, J. Colloid Interface Sci. 105, 216 (1985)] of
      charged colloids, OLPB theory is applicable to thermodynamic states at which
      conventional, Debye-Huckel (DH) linearization of the Poisson-Boltzmann equation
      is rendered invalid by violation of the condition that the electrostatic coupling
      energy of a mobile ion be much smaller than its thermal energy throughout space,
      |nu(alpha)e psi(r)|<<k(B)T. As a demonstration of its applicability to flexible
      polyelectrolytes, OLPB theory is applied to a concentrated solution of freely
      jointed chains. The osmotic pressure is computed at various reservoir ionic
      strengths and compared with results from the conventional DH model for
      polyelectrolytes. Through comparison with the cylindrical cell model for
      polyelectrolytes, it is demonstrated that the OLPB model yields the correct
      osmotic pressure behavior with respect to nonlinear theory where conventional DH
      theory fails, namely at large ratios of mean counterion density to reservoir salt
      density, when the Donnan potential is large.

PMID- 15485215
TI  - Hydrogen bond mediated rotor-ring coupling in acetic acid-benzoic acid mixed
      dimer.
AB  - In this work we demonstrate that a doubly hydrogen-bonded interface of two
      carboxylic acid groups behaves as efficient conduit to transmit the rotor effects
      for IVR acceleration in a phenyl ring. The phenomenon has been demonstrated by
      measuring the resolved emission spectra following SVL excitations in S(1) of a
      1:1 mixed dimer between acetic acid and benzoic acid. The role of the methyl
      rotor has been ascertained by comparing the results with those obtained for an
      analogous dimeric system between formic acid and benzoic acid.

PMID- 15485216
TI  - Quantum-classical limit of quantum correlation functions.
AB  - A quantum-classical limit of the canonical equilibrium time correlation function
      for a quantum system is derived. The quantum-classical limit for the dynamics is
      obtained for quantum systems comprising a subsystem of light particles in a bath
      of heavy quantum particles. In this limit the time evolution of operators is
      determined by a quantum-classical Liouville operator, but the full equilibrium
      canonical statistical description of the initial condition is retained. The
      quantum-classical correlation function expressions derived here provide a way to
      simulate the transport properties of quantum systems using quantum-classical
      surface-hopping dynamics combined with sampling schemes for the quantum
      equilibrium structure of both the subsystem of interest and its environment

PMID- 15485217
TI  - Accuracy of gates in a quantum computer based on vibrational eigenstates.
AB  - A model is developed to study the properties of a quantum computer that uses
      vibrational eigenstates of molecules to implement the quantum information bits
      and shaped laser pulses to apply the quantum logic gates. Particular emphasis of
      this study is on understanding how the different factors, such as properties of
      the molecule and of the pulse, can be used to affect the accuracy of quantum
      gates in such a system. Optimal control theory and numerical time-propagation of
      vibrational wave packets are employed to obtain the shaped pulses for the gates
      NOT and Hadamard transform. The effects of the anharmonicity parameter of the
      molecule, the target time of the pulse and of the penalty function are
      investigated. Influence of all these parameters on the accuracy of qubit
      transformations is observed and explained. It is shown that when all these
      parameters are carefully chosen the accuracy of quantum gates reaches 99.9%.

PMID- 15485218
TI  - Accurate calculation of core-electron binding energies: multireference
      perturbation treatment.
AB  - Multireference perturbation theory (MRPT) with multiconfigurational self
      consistent field (MCSCF) reference functions is applied to the calculations of
      core-electron binding energies (CEBEs) of atoms and molecules. Orbital
      relaxations in a core-ionized state and electron correlation are both taken into
      account in a conventional MCSCF-MRPT procedure. In the MCSCF calculation, the
      target core ionized state is directly optimized as an excited state and this
      treatment can completely prevent a variational collapse. Multireference Moller
      Plesset perturbation theory and multiconfigurational self-consistent field
      reference quasidegenerated perturbation theory were used to treat electron
      correlation. The present method quite accurately reproduced the 1s CEBEs of CH4,
      NH3, H2O, and FH; the average deviation from the experimental data is 0.11 eV
      using Ahlrichs' VTZ basis set. The C 1s and O 1s CEBEs of formic acid and acetic
      acid were calculated and the results are consistent with the bonding characters
      of the atoms in these molecules. The present procedure can also be applied to
      CEBEs of higher angular momentum orbitals by including spin-orbit coupling. The
      calculated CEBEs of Ar 2p, HCl 2p, Kr 3d, and HBr 3d are in reasonable agreement
      with the available experimental values. In the calculation of the 3d CEBEs, a
      relativistic correction significantly improves the agreements. The effect of
      polarization functions is also discussed.

PMID- 15485219
TI  - Calculations of static and dynamic polarizabilities of excited states by means of
      density functional theory.
AB  - We present density functional theory and calculations for excited state second
      order, static or dynamic, properties. The excited state properties are identified
      from a double residue of a cubic response function. The performance of various
      functionals, including the generalized gradient approximation and fractional
      exact Hartree-Fock exchange, is compared to coupled cluster calculations.
      Applications on excited state polarizabilities of s-tetrazine and pyrimidine show
      a good agreement with ab initio correlated, coupled cluster, results.

PMID- 15485220
TI  - Spectral implementation of some quantum algorithms by one- and two-dimensional
      nuclear magnetic resonance.
AB  - Quantum information processing has been effectively demonstrated on a small
      number of qubits by nuclear magnetic resonance. An important subroutine in any
      computing is the readout of the output. "Spectral implementation" originally
      suggested by Z. L. Madi, R. Bruschweiler, and R. R. Ernst [J. Chem. Phys. 109,
      10603 (1999)], provides an elegant method of readout with the use of an extra
      "observer" qubit. At the end of computation, detection of the observer qubit
      provides the output via the multiplet structure of its spectrum. In spectral
      implementation by two-dimensional experiment the observer qubit retains the
      memory of input state during computation, thereby providing correlated
      information on input and output, in the same spectrum. Spectral implementation of
      Grover's search algorithm, approximate quantum counting, a modified version of
      Berstein-Vazirani problem, and Hogg's algorithm are demonstrated here in three-
      and four-qubit systems.

PMID- 15485221
TI  - Density functional theory for hyperfine coupling constants with the restricted
      unrestricted approach.
AB  - This work presents derivation, implementation, and the first applications of the
      restricted-unrestricted approach based on restricted Kohn-Sham formalism for
      evaluation of hyperfine coupling constants. By using the spin-restricted Kohn
      Sham method the well-known spin contamination problem existing in the
      unrestricted Kohn-Sham formalism is avoided and a proper description of spin
      polarization is achieved via the restricted-unrestricted approach without
      introducing spin contamination into the evaluation of the hyperfine coupling
      constants. The performance of the proposed formalism is evaluated for a set of
      organic radicals and transition metal compounds. The results of this
      investigation indicate promising accuracy of the restricted-unrestricted approach
      for calculation of the isotropic hyperfine coupling constants in organic radicals
      as well as transition metal compounds.

PMID- 15485222
TI  - Triplet instability in doublet systems.
AB  - Some problems associated with unrestricted wave functions for open-shell
      molecules are discussed in the contest of coupled-cluster calculation of
      molecular properties. Particular attention is given to a phenomenon akin to the
      "triplet instability" of closed-shell molecules, where the approximate spin
      pairing of a nominal pair of electrons in the unrestricted Hartree-Fock wave
      function begins to give way to significant spin polarization. This problem-which
      gives rise to pronounced spin contamination-is discussed from the point of view
      of orbital instability and occupation numbers of the charge density matrix. The
      onset, rather than the magnitude of the spin contamination is analyzed in detail
      for diatomics, especially heteronuclear cases where the transition to significant
      spin contamination does not occur discontinuously. It is shown that the
      qualitative description of this phenomenon satisfactorily explains anomalous
      results for NO and PO, although the magnitude of spin contamination in these
      molecules is significantly less than in other cases where anomalous results are
      not observed. It appears that calculations of equilibrium molecular properties
      using coupled-cluster methods based on unrestricted Hartree-Fock reference should
      be monitored carefully for any molecule containing a multiple bond, especially
      when the bonded pair of atoms appear in different rows of the periodic table.

PMID- 15485223
TI  - The behavior of density functionals with respect to basis set. I. The correlation
      consistent basis sets.
AB  - The accuracy of density functional theory in the description of geometries and
      atomization energies has been assessed by comparison to experimental data for a
      series of first-row closed-shell molecules. Six commonly used functionals (B3LYP,
      B3PW91, B3P86, BLYP, BPW91, BP86) were investigated in combination with the
      correlation-consistent basis sets [cc-pVxZ and aug-cc-pVxZ where x=D(2), T(3),
      Q(4), 5]. The convergence of molecular properties with respect to increasing
      basis set size has been examined. A full statistical error analysis has been
      performed, assessing the success of each functional with respect to each basis
      set in terms of both accuracy and precision. Overall, there is smooth convergence
      towards the Kohn-Sham limit for the hybrid functionals B3LYP and B3PW91, whereas
      the nonlocal functionals are relatively insensitive to basis set choice.

PMID- 15485224
TI  - Multiscale quantum propagation using compact-support wavelets in space and time.
AB  - Orthogonal compact-support Daubechies wavelets are employed as bases for both
      space and time variables in the solution of the time-dependent Schrodinger
      equation. Initial value conditions are enforced using special early-time wavelets
      analogous to edge wavelets used in boundary-value problems. It is shown that the
      quantum equations may be solved directly and accurately in the discrete wavelet
      representation, an important finding for the eventual goal of highly adaptive
      multiresolution Schrodinger equation solvers. While the temporal part of the
      basis is not sharp in either time or frequency, the Chebyshev method used for
      pure time-domain propagations is adapted to use in the mixed domain and is able
      to take advantage of Hamiltonian matrix sparseness. The orthogonal separation
      into different time scales is determined theoretically to persist throughout the
      evolution and is demonstrated numerically in a partially adaptive treatment of
      scattering from an asymmetric Eckart barrier.

PMID- 15485225
TI  - Coherent switching with decay of mixing: an improved treatment of electronic
      coherence for non-Born-Oppenheimer trajectories.
AB  - The self-consistent decay-of-mixing (SCDM) semiclassical trajectory method for
      electronically nonadiabatic dynamics is improved by modifying the switching
      probability that determines the instantaneous electronic state toward which the
      system decoheres. This method is called coherent switching with decay of mixing
      (CSDM), and it differs from the previously presented SCDM method in that the
      electronic amplitudes controlling the switching of the decoherent state are
      treated fully coherently in the electronic equations of motion for each complete
      passage through a strong interaction region. It is tested against accurate
      quantum mechanical calculations for 12 atom-diatom scattering test cases. Also
      tested are the SCDM method and the trajectory surface hopping method of Parlant
      and Gislason that requires coherent passages through each strong interaction
      region, and which we call the "exact complete passage" trajectory surface hopping
      (ECP-TSH) method. The results are compared with previously presented results for
      the fewest switches with time uncertainty and Tully's fewest switches (TFS)
      surface hopping methods and the semiclassical Ehrenfest method. We find that the
      CSDM method is the most accurate of the semiclassical trajectory methods tested.
      Including coherent passages improves the accuracy of the SCDM method (i.e., the
      CSDM method is more accurate than the SCDM method) but not of the trajectory
      surface hopping method (i.e., the ECP-TSH method is not more accurate on average
      than the TFS method).

PMID- 15485227
TI  - Quantum wave-packet dynamics of H+HLi scattering: reaction cross section and
      thermal rate constant.
AB  - The channel specific and initial state-selected reaction cross section and
      temperature-dependent rate constant for the title system is calculated with the
      aid of a time-dependent wave-packet approach and using the ab initio potential
      energy surface of Dunne et al. [Chem. Phys. Lett. 336, 1 (2001)]. All partial
      wave contributions up to the total angular momentum J=74 are explicitly
      calculated within the coupled states (CS) approximation. Companion calculations
      are also carried out employing the standard as well as the uniform J-shifting
      (JS) approximation. The overall variation of reaction cross sections corresponds
      well to the behavior of a barrierless reaction. The hydrogen exchange channel
      yielding HLi+H products is seen to be more favored over the HLi depletion channel
      yielding Li+H(2) products at low and moderate collision energies. Sharp resonance
      features are observed in the cross-section results for the HLi depletion channel
      at low energies. Resonance features in the reaction cross sections average out
      with various partial-wave contributions, when compared to the same observed in
      the individual reaction probability curve. Except near the onset of the reaction,
      the vibrational and rotational excitation of the reagent HLi, in general, does
      not dramatically influence the reactivity of either channel. The thermal rate
      constants calculated up to 4000 K show nearly Arrhenius type behavior. The rate
      constant decreases with vibrational excitation of the reagent HLi, indicating
      that the cold HLi molecules are efficiently depleted in the reactive encounter
      with H at relatively low temperatures. The results obtained from the JS
      approximation are found to agree well qualitatively with the CS results.

PMID- 15485226
TI  - Correlation energy of many-electron systems: a modified Colle-Salvetti approach.
AB  - The Colle and Salvetti approach [Theo. Chim. Acta 37, 329 (1975)] to the
      calculation of the correlation energy of a system is modified in order to
      explicitly include into the theory the kinetic contribution to the correlation
      energy. This is achieved by deducing from a many electrons wave function,
      including the correlation effects via a Jastrow factor, an approximate expression
      of the one-electron reduced density matrix. Applying the latter to the
      homogeneous electron gas, an analytic expression of the correlation kinetic
      energy is derived. The total correlation energy of such a system is then deduced
      from its kinetic contribution inverting a standard procedure. At variance of the
      original Colle-Salvetti theory, the parameters entering in both the kinetic
      correlation and the total correlation energies are determined analytically,
      leading to a satisfactory agreement with the results of Perdew and Wang [Phys.
      Rev. B 45, 13244 (1992)]. The resulting (parameter-free) expressions give rise to
      a modified-local-density approximation that can be used in self-consistent
      density-functional calculations. We have performed such calculations for a large
      set of atoms and ions and we have found results for the correlation energies and
      for the ionization potentials which improve those of the standard local-density
      approximation.

PMID- 15485228
TI  - Photoelectron spectroscopy and density functional theory of puckered ring
      structures of Group 13 metal-ethylenediamine.
AB  - The ethylenediamine (en) complexes of Al, Ga, and In atoms were prepared in laser
      vaporization supersonic molecular beams and studied with pulsed field ionization
      zero electron kinetic energy photoelectron spectroscopy and density functional
      theory. Several conformers of each metal complex are obtained by B3LYP
      calculations, and a five-membered cyclic structure is identified by combining the
      experimental measurements and theoretical calculations. Adiabatic ionization
      potentials, vibrational frequencies, and bond dissociation energies are
      determined for the ring structure. The ionization potentials of the Al, Ga, and
      In species are measured to be 32 784 (5), 33 324 (5), and 33 637 (7) cm(-1),
      respectively, and metal-ligand dissociation energies of the ionic and neutral
      complexes are calculated to be 60.2/16.2 (Al(+)/Al), 55.5/13.0 (Ga(+)/Ga), and
      50.0/11.4 (In(+)/In) kcal mol(-1). Metal-ligand stretch and bend as well as a
      number of ligand-based vibrations are measured. Harmonic frequencies and
      anharmonicities of the M(+)-N (M=Al,Ga,In) stretch are determined for all three
      M(+)-en ions and the C-C-N bend of Ga(+)-en and In(+)-en. In comparison to
      monodentate methylamine, the bidentate binding of ethylenediamine leads to a
      significantly lower ionization potential and higher metal-ligand bond strength of
      the metal complexes.

PMID- 15485229
TI  - Evolution spectrum of C60 isomers in buffer gas.
AB  - The energy spectrum of C60 nonclassic fullerenes with single heptagon defects
      calculated by Brenner empirical potential is found to submerge into the spectrum
      of classic fullerenes. Geometry analysis indicates that these nonclassic
      fullerene isomers can be more attainable than classic fullerenes at higher Stone
      Wales (SW) stacks. Molecular dynamic simulations of the C60 isomer evolution in
      He buffer gas at 2500 K demonstrate that nonclassic fullerenes, especially those
      with heptagon defects, play an important role in the dynamics of C60 annealing,
      and that the Stone-Wales stack-by-stack transition mainly occurs at lower SW
      stacks. A non-SW multistep rearrangement is first observed in the simulation with
      its transition sequence and intermediate state presented in detail.

PMID- 15485230
TI  - Radial subshell splittings and double-zeta functions in many-electron atoms.
AB  - When the electron-electron interaction is explicitly considered in many-electron
      atoms, the average subshell radius<r>nl splits into two different radii, inner
      radius <r< >nl and outer radius <r> >nl, where n and l are the principal and
      azimuthal quantum numbers. For the 102 atoms He through Lr in their ground
      states, the radii <r< >nl and <r< >nl are systematically examined at the Hartree
      Fock limit level. For a subshell nl, two exponents zeta<nl(est) and zeta>nl(est)
      estimated from these radii have good linear correlations with variationally
      determined exponents zeta<nl(var) and zeta>nl(var) of double-zeta Slater-type
      functions.

PMID- 15485231
TI  - New approximations for calculating dispersion coefficients.
AB  - Improved approaches for finding approximate values of dispersion coefficients are
      proposed. They are based on scaling the values of time-dependent Hartree-Fock
      (TDHF) dispersion coefficients by factors that use the ratio of the estimated
      true value and the TDHF value of static dipole polarizabilities. It is shown that
      for a set of 14 atoms and molecules the average absolute-value deviation of the
      estimated two-body isotropic dispersion coefficients with respect to the dipole
      oscillator strength distribution results is smaller than 1.0% for two of our
      approaches. For three-body isotropic dispersion coefficients the corresponding
      deviations are smaller than 1.2%. Our approximations work particularly well
      compared to approximations proposed by other researchers in cases where the TDHF
      results differ from the reference values by more than 10%.

PMID- 15485232
TI  - The nonmetallicity of molybdenum clusters.
AB  - Molybdenum clusters consisting of 2-55 atoms were investigated using density
      functional theory calculations with a plane-wave basis set. The results show that
      the linear and planar molybdenum clusters have a strong tendency to form dimers.
      This tendency results in the formation of alternate short and long bonds within a
      linear cluster, in which the strength of these short bonds is covalent.
      Therefore, the linear and planar Mo clusters exhibit significant nonmetallic
      characteristics. Furthermore, the linear and planar Mo clusters show a strong
      even-odd effect in binding energy with the even-numbered clusters being more
      stable than their neighboring odd-numbered clusters. On the other hand, the even
      odd effect in the energy gap between the highest occupied and the lowest
      unoccupied molecular orbitals, i.e., the HOMO-LUMO energy gap, for the linear and
      the planar clusters is different. The odd-numbered linear clusters and even
      numbered planar clusters have larger HOMO-LUMO energy gaps than their
      corresponding neighboring clusters.

PMID- 15485233
TI  - A three-dimensional He-NaH potential energy surface for rovibrational energy
      transfer studies.
AB  - A three-dimensional potential energy surface for the He-NaH van der Waals complex
      is calculated at the coupled cluster singles-and-doubles with noniterative
      inclusion of connected triples [CCSD(T)] level of theory. Estimates of CCSD(T)
      interaction energies for an infinitely large basis set is obtained using a basis
      set extrapolation scheme. The He-NaH potential energy surface is much different
      than the He-LiH surface. In particular, the He-NaH system has a binding energy of
      De=19.73 cm(-1) in comparison to De=176.7 cm(-1) for He-LiH. These minima are at
      the theta=180 degrees linear geometry where the helium is located at the metal
      end of the metal hydride. The He-NaH and He-LiH potentials are very similar for
      the theta=0 degrees linear geometry. The He-NaH potential energy surface supports
      one vibrational bound state with E=-1.48 cm(-1). Since this energy is smaller
      than the accuracy of the potential energy surface, the existence of a bound He
      NaH complex is questionable.

PMID- 15485234
TI  - Electronic spectra of iron monohydride in the infrared near 1.35 and 1.58 microm.
AB  - The complex, many-line spectrum of FeH, lying in the infrared region between 5500
      and 7500 cm(-1), has been shown to consist of two separate electronic
      transitions: E (4)Pi-X (4)Delta and E (4)Pi-A (4)Pi. High resolution Fourier
      transform spectra from thermal emission have been rotationally analyzed in
      detail. Lambda doubling in both the E (4)Pi and A (4)Pi states is considerable.
      The experimentally determined energies and bond lengths of the newly
      characterized states are in good agreement with theoretical predictions.

PMID- 15485235
TI  - Calculated optical and magnetic properties of hexafluorouranate (V) anion: UF- 6.
AB  - Our ab initio all-electron Dirac-Fock and the corresponding nonrelativistic limit
      calculations performed at four U-F bond distances yield for octahedral UF(6) (-)
      the optimized U-F bond distance of 2.091 and 2.088 A, respectively. We have also
      performed Dirac scattered wave calculations at the optimized U-F bond distances
      using the first-order pertubational procedure to obtain the Zeeman and hyperfine
      magnetic tensors for the octahedral anion UF(6) (-). The calculated isotropic
      Zeeman tensor of Deltag=-2.87 is in fairly good agreement with the value of
      Deltag=-2.78+/-0.10 obtained in electron spin resonance experiments on the
      H(3)O(+)UF(6) (-) adduct and the unpaired electron-spin spends approximately 2.5%
      of its time on the fluorine 2p(3/2) spinors. The calculated relativistic
      transition energies of the near-IR and visible absorption bands are also in good
      agreement with the experimental results. The octahedral uranium hexafluoride
      anion has a simple crystal field f(1) configuration; however, relativistic four
      component wave functions are necessary to interpret correctly the available
      magnetic data, while a relativistic treatment taking into account double group
      symmetrized basis functions should suffice for the interpretation of the optical
      data.

PMID- 15485236
TI  - A mass spectrometric and density functional study of the intermetallic molecules
      AuBe, AuMg, and AuCa.
AB  - The intermetallic molecules AuBe and AuCa were identified by means of the Knudsen
      Effusion Mass Spectrometry technique in the high-temperature vapors produced by
      vaporizing Au-Be-Ca alloys of proper composition. The gaseous equilibria
      AuBe(g)+Au(g)=Au(2)(g)+Be(g) and AuCa(g)+Au(g)=Au(2)(g)+Ca(g) were studied in the
      temperature ranges 1720-1841 K and 1669-1841 K, respectively, by monitoring the
      partial pressures of all the species involved. The equilibrium data were analyzed
      by the third-law method, obtaining for the first time the dissociation energy
      D(0) ( composite function) of the two intermetallic species: D(0) ( composite
      function)(AuBe)=234.0+/-4.0 kJ/mol; D(0) ( composite function)(AuCa)=246.7+/-4.0
      kJ/mol. These values are significantly higher than the recently published D(0) (
      composite function) of the species AuMg (175.4+/-2.7 kJ/mol). Furthermore, the
      ionization energies (IE) of AuBe, AuMg, and AuCa were obtained by measuring the
      electron impact ionization efficiency curves, IE(AuBe)=7.5+/-0.3 eV,
      IE(AuMg)=6.7+/-0.3 eV, and IE(AuCa)=5.5+/-0.3 eV. Theoretical calculations were
      also carried out for these species by density functional theory methods (PW91 and
      BP86) used in conjunction with Stuttgart relativistic effective core potentials.
      Both functionals were found to perform very well in reproducing experimental D(0)
      ( composite function), IE, and molecular parameters.

PMID- 15485237
TI  - Structural and electronic properties of Si n, Si n+, and AlSi n-1 (n=2-13)
      clusters: theoretical investigation based on ab initio molecular orbital theory.
AB  - The geometric and electronic structures of Si(n), Si(n) (+), and AlSi(n-1)
      clusters (2< or =n< or =13) have been investigated using the ab initio molecular
      orbital theory under the density functional theory formalism. The hybrid exchange
      correlation energy function (B3LYP) and a standard split-valence basis set with
      polarization functions [6-31G(d)] were employed for this purpose. Relative
      stabilities of these clusters have been analyzed based on their binding energies,
      second difference in energy (Delta (2)E) and fragmentation behavior. The
      equilibrium geometry of the neutral and charged Si(n) clusters show similar
      structural growth. However, significant differences have been observed in the
      electronic structure leading to their different stability pattern. While for
      neutral clusters, the Si(10) is magic, the extra stability of the Si(11) (+)
      cluster over the Si(10) (+) and Si(12) (+) bears evidence for the magic behavior
      of the Si(11) (+) cluster, which is in excellent agreement with the recent
      experimental observations. Similarly for AlSi(n-1) clusters, which is
      isoelectronic with Si(n) (+) clusters show extra stability of the AlSi(10)
      cluster suggesting the influence of the electronic structures for different
      stabilities between neutral and charged clusters. The ground state geometries of
      the AlSi(n-1) clusters show that the impurity Al atom prefers to substitute for
      the Si atom, that has the highest coordination number in the host Si(n) cluster.
      The fragmentation behavior of all these clusters show that while small clusters
      prefers to evaporate monomer, the larger ones dissociate into two stable clusters
      of smaller size.

PMID- 15485238
TI  - Effect of absolute laser phase on reaction paths in laser-induced chemical
      reactions.
AB  - Potential surfaces, dipole moments, and polarizabilities are calculated by ab
      initio methods [unrestricted MP2(full)/6-311++G(2d,2p)] along the reaction paths
      of the F+CH4 and Cl+CH4 reaction systems. It is found that in general dipole
      moments and polarizabilities exhibit peaks near the transition state. In the case
      of X=F these peaks are on the products side and in the case of X=Cl they are on
      the reactants side indicating an early transition state in the case of fluorine
      and a late transition state in the case of chlorine. An analysis of the geometric
      changes along the reaction paths reveals a one-to-one correspondence between the
      peaks in the electric properties and peaks in the rate of change of certain
      internal geometric coordinates along the reaction path. Interaction with short
      infrared intense laser fields pulses leads to the possibility of interferences
      between the dipole and polarizability laser-molecule interactions as a function
      of laser phase. The larger dipole moment in the Cl+CH4 reaction can lead to the
      creation of deep wells (instead of energy barriers) and new strongly bound states
      in the transition state region. This suggests possible coherent control of the
      reaction path as a function of the absolute phase of the incident field, by
      significant modification of the potential surfaces along the reaction path and,
      in particular, in the transition state region.

PMID- 15485239
TI  - Dissociative multiphoton ionization of NO2 studied by time-resolved imaging.
AB  - We have studied dissociative multiphoton ionization of NO2 by time-resolved
      velocity map imaging in a two-color pump-probe experiment using the 400 and 266
      nm harmonics of a regeneratively amplified titanium-sapphire laser. We observe
      that most of the ion signal appears as NO+ with approximately 0.28 eV peak
      kinetic energy. Approximately 600 fs period oscillations indicative of wave
      packet motion are also observed in the NO+ decay. We attribute the signal to two
      competitive mechanisms. The first involving three-photon 400 nm absorption
      followed by dissociative ionization of the pumped state by a subsequent 266 nm
      photon. The second involving one-photon 400 nm absorption to the 2B2 state of NO2
      followed by two-photon dissociative ionization at 266 nm. This interpretation is
      derived from the observation that the total NO+ ion signal exhibits biexponential
      decay, 0.72 exp(-t/90+/-10)+0.28 exp(-t/4000+/-400), where t is the 266 nm delay
      in femtoseconds. The fast decay of the majority of the NO+ signal suggests a
      direct dissociation via the bending mode of the pumped state. .

PMID- 15485240
TI  - Vibrational dynamics of medium strength hydrogen bonds: Fourier transform
      infrared spectra and band contour analysis of the DF stretching region of (CH2)2S
      DF.
AB  - Fourier transform infrared spectra of the nu(s) band of the (CH2)(2)S-DF complex
      have been recorded at 0.1-0.5 cm(-1) resolution in a cooled cell and in a
      supersonic jet expansion seeded with argon. A sufficient density of (CH(2))(2)S
      DF heterodimers is produced by a double injection nozzle device, which limits the
      possibility of reaction between thiirane and DF before the expansion. The
      observation of partially resolved PQR branch structures at cell temperatures as
      high as 252 K indicates relatively small effective line widths, which allow a
      detailed analysis of the underlying vibrational couplings and of the structural
      properties of the complex. The analysis of cell and free jet spectra in the
      temperature range 50-250 K is performed with a software package for the
      simulation and fitting of multiple hot band progressions in asymmetric rotors.
      The analysis reveals that the three low frequency hydrogen-bond modes are
      strongly coupled to the DF stretch with anharmonic coupling constants, which
      indicates a strengthening of the hydrogen bond upon vibrational excitation of DF.
      Rovibrational parameters and a reliable upper bound for the homogeneous line
      width have been extracted.

PMID- 15485241
TI  - The acidity of tert-butyl alcohol in near- and supercritical water: a polarizable
      continuum approach.
AB  - We use a polarizable continuum approach to study the acidity of tert-butyl
      alcohol in water at ambient, near-critical, and supercritical conditions. In the
      most straightforward calculation, the bare ionic species (the tert-butoxy anion
      and the hydronium cation) are placed in cavities surrounded by a dielectric
      continuum, using a dielectric constant corresponding to the state point. A second
      method is first to solvate these ions with a small number of explicit water
      molecules and then surround this cluster with the dielectric. This is the cluster
      continuum approach. We discuss the advantages and disadvantages of these two
      schemes and we also discuss various ways in which the second method can be
      implemented. No method showed quantitative agreement with all available
      experimental results but the first, straightforward method was the most
      successful in predicting the correct trends. From both a numerical and a
      theoretical point of view, we believe this is the method of choice.

PMID- 15485243
TI  - The effects of connectivity, coherence, and trapping on energy transfer in simple
      light-harvesting systems studied using the Haken-Strobl model with diagonal
      disorder.
AB  - The problem of electronic energy transfer in a network of two-level systems
      coupled to a single trapping site is investigated using a simple Haken-Strobl
      model with diagonal disorder. The goal is to illustrate how the trapping time
      T(trap), coherence time T(d), and molecular topology all affect the overall
      efficiency of a light-harvesting network. Several issues are identified that need
      to be considered in the design of an optimal energy transfer network, including
      the dephasing-induced decoupling the trap from the rest of the network, the
      nonlinear dependence of trapping rate on the coherence time, and the role of
      network size and connectivity in determining the effect of the coherence time on
      efficiency. There are two main conclusions from this work. First, there exists an
      optimum combination of trapping time and coherence time, which will give the most
      rapid population transfer to the trap. These values are not in general the
      shortest trapping time and the longest coherence time, as would be expected based
      on rate equation models and/or simple considerations from previous analytical
      results derived for the Haken-Strobl model in an infinite system. Second, in the
      coherent regime, where T(d) is longer than the other relevant timescales,
      population trapping in a finite system can be suppressed by quantum interference
      effects, whose magnitude is sensitive to the molecular geometry. Suggestions for
      possible methods of observing such effects are discussed. These results provide a
      qualitative framework for quantum coherence and molecular topology into account
      for the design of covalent light-harvesting networks with high energy transfer
      efficiencies.

PMID- 15485242
TI  - Spectroscopic identification of the CO-H2O 2-1 cluster trapped in an argon
      matrix.
AB  - The infrared spectra of the carbon monoxide-water cluster as well as the CO
      monomer and dimer in an argon matrix at cryogenic temperatures have been
      reinvestigated on the basis of the isotope substitution experiment with 12CO and
      13CO. Lines due to the CO-H2O 2-1 cluster in the matrix have been unambiguously
      identified in the CO and OH stretching regions. The isotope effect on the
      vibrational frequency of the cluster is observed in the CO stretching vibration
      but neither in the symmetric nor antisymmetric OH stretching vibrations. Each of
      the two vibrational lines due to the two CO vibrations of the CO-H2O 2-1 cluster
      is examined by comparing the expected spectral features at a 12CO/13CO ratio on a
      simulation with those observed experimentally. The migration of the trapped
      molecules (CO and H2O) in the matrix is discussed, in which the observed spectral
      change with the deposition temperature from 14 K to 30 K is explained.

PMID- 15485244
TI  - Nucleation near the spinodal: limitations of mean field density functional
      theory.
AB  - We investigate the diverging size of the critical nucleus near the spinodal using
      the gradient theory (GT) of van der Waals and Cahn and Hilliard and mean field
      density functional theory (MFDFT). As is well known, GT predicts that at the
      spinodal the free energy barrier to nucleation vanishes while the radius of the
      critical fluctuation diverges. We show numerically that the scaling behavior
      found by Cahn and Hilliard for these quantities holds quantitatively for both GT
      and MFDFT. We also show that the excess number of molecules Deltag satisfies Cahn
      Hilliard scaling near the spinodal and is consistent with the nucleation theorem.
      From the latter result, it is clear that the divergence of Deltag is due to the
      divergence of the mean field isothermal compressibility of the fluid at the
      spinodal. Finally, we develop a Ginzburg criterion for the validity of the mean
      field scaling relations. For real fluids with short-range attractive
      interactions, the near-spinodal scaling behavior occurs in a fluctuation
      dominated regime for which the mean field theory is invalid. Based on the
      nucleation theorem and on Wang's treatment of fluctuations near the spinodal in
      polymer blends, we infer a finite size for the critical nucleus at the
      pseudospinodal identified by Wang.

PMID- 15485245
TI  - Identifiability analysis of models for reversible intermolecular two-state
      excited-state processes coupled with species-dependent rotational diffusion
      monitored by time-resolved fluorescence depolarization.
AB  - A deterministic identifiability analysis of the kinetic model for a reversible
      intermolecular two-state excited-state process with species-dependent rotational
      diffusion described by Brownian reorientation is presented. The cases of both
      spherically and cylindrically symmetric rotors, with no change in the principal
      axes of rotation on interconversion in the latter case, are specifically
      considered. The identifiability analysis is carried out in terms of compartmental
      modeling based on the S(t) identical with I( parallel)(t)+2I( perpendicular)(t)
      and D(t) identical with I( parallel)(t)-I( perpendicular)(t) functions, where I(
      parallel)(t) and I( perpendicular)(t) are the delta-response functions for
      fluorescence, polarized, respectively, parallel and perpendicular to the electric
      vector of linearly polarized excitation. It is shown that, from polarized time
      resolved fluorescence data collected at two concentrations of coreactant and
      three appropriately chosen emission wavelengths, (a) a unique set of rate
      constants for the overall excited-state process is always obtained by making use
      of polarized measurements and (b) the rotational diffusion constants and
      geometrical factors associated with the different anisotropy decay components can
      be uniquely determined and assigned to each species. The geometrical factors are
      determined by the absorption and emission transitions in the two rotating
      species. For spherical rotors, these factors depend directly on the relative
      orientations of the transition moments, while for cylindrically symmetric rotors
      they depend on the orientations with respect to each other and to the symmetry
      axis.

PMID- 15485246
TI  - Ions in water: the microscopic structure of a concentrated HCl solution.
AB  - A neutron diffraction experiment with isotopic H/D substitution on a concentrated
      HCl/H2O solution is presented. The full set of partial structure factors is
      extracted, by combining the diffraction data with a Monte Carlo simulation. This
      allows us to investigate both the changes of the water structure in the presence
      of ions and their solvation shell, overcoming the limitations of standard
      diffraction experiments. It is found that the interaction with the solutes
      affects the tetrahedral network of hydrogen bonded water molecules, in a manner
      similar to the application of an external pressure to pure water, although HCl
      seems less effective than other solutes, such as NaOH, at the same concentration.
      Consistent with experimental and theoretical data, the number of water molecules
      in the solution is not sufficient to completely dissociate the acid molecule. As
      a consequence, both dissociated H+ and Cl- ions and undissociated HCl molecules
      coexist in the sample, and this mixture is correctly reproduced in the simulation
      box. In particular, the hydrated H+ ions, forming a H3O+ complex, participate in
      three strong and short hydrogen bonds, while a well-defined hydration shell is
      found around the chlorine ion. These results are not consistent with the findings
      of early diffraction experiments on the same system and could only be obtained by
      combining high quality experimental data with a proper computer simulation.

PMID- 15485247
TI  - Phonons in suspensions of hard sphere colloids: volume fraction dependence.
AB  - The propagation of sound waves in suspensions of hard sphere colloids is studied
      as a function of their volume fraction up to random close packing using Brillouin
      light scattering. The rich experimental phonon spectra of up to five phonon modes
      are successfully described by theoretical calculations based on the multiple
      scattering method. Two main types of phonon modes are revealed: Type A modes are
      acoustic excitations which set up deformations in both the solid (particles) and
      the liquid (solvent) phases; for type B modes the stress and strain are
      predominantly localized near the interface between the solid particles and the
      surrounding liquid (interface waves). While the former become harder (increase
      their effective sound velocity) as the particle volume fraction increases the
      latter become softer (the corresponding sound velocity decreases).

PMID- 15485248
TI  - Water motion in reverse micelles studied by quasielastic neutron scattering and
      molecular dynamics simulations.
AB  - Motion of water molecules in Aerosol OT [sodium bis(2-ethylhexyl) sulfosuccinate,
      AOT] reverse micelles with water content w(0) ranging from 1 to 5 has been
      explored both experimentally through quasielastic neutron scattering (QENS) and
      with molecular dynamics (MD) simulations. The experiments were performed at the
      energy resolution of 85 microeV over the momentum transfer (Q) range of 0.36-2.53
      A(-1) on samples in which the nonpolar phase (isooctane) and the AOT alkyl chains
      were deuterated, thereby suppressing their contribution to the QENS signal. QENS
      results were analyzed via a jump-diffusion/isotropic rotation model, which fits
      the results reasonably well despite the fact that confinement effects are not
      explicitly taken into account. This analysis indicates that in reverse micelles
      with low-water content (w(0)=1 and 2.5) translational diffusion rate is too slow
      to be detected, while for w(0)=5 the diffusion coefficient is much smaller than
      for bulk water. Rotational diffusion coefficients obtained from this analysis
      increase with w(0) and are smaller than for bulk water, but rotational mobility
      is less drastically reduced than translational mobility. Using the Faeder/Ladanyi
      model [J. Phys. Chem. B 104, 1033 (2000)] of reverse micelle interior, MD
      simulations were performed to calculate the self-intermediate scattering function
      F(S)(Q,t) for water hydrogens. Comparison of the time Fourier transform of this
      F(S)(Q,t) with the QENS dynamic structure factor S(Q,omega), shows good agreement
      between the model and experiment. Separate intermediate scattering functions F(S)
      (R)(Q,t) and F(S) (CM)(Q,t) were determined for rotational and translational
      motion. Consistent with the decoupling approximation used in the analysis of QENS
      data, the product of F(S) (R)(Q,t) and F(S) (CM)(Q,t) is a good approximation to
      the total F(S)(Q,t). We find that the decay of F(S) (CM)(Q,t) is nonexponential
      and our analysis of the MD data indicates that this behavior is due to lower
      water mobility close to the interface and to confinement-induced restrictions on
      the range of translational displacements. Rotational relaxation also exhibits
      nonexponential decay. However, rotational mobility of O-H bond vectors in the
      interfacial region remains fairly high due to the lower density of water-water
      hydrogen bonds in the vicinity of the interface.

PMID- 15485249
TI  - Decay of correlation functions in hard-sphere mixtures: structural crossover.
AB  - We investigate the decay of pair correlation functions in a homogeneous (bulk)
      binary mixture of hard spheres. At a given state point the asymptotic decay r-
      >infinity of all three correlation functions is governed by a common exponential
      decay length and a common wavelength of oscillations. Provided the mixture is
      sufficiently asymmetric, size ratios q less than or approximately 0.7, we find
      that the common wavelength reflects either the size of the small or that of the
      big spheres. By analyzing the (complex) poles of the partial structure factors we
      find a sharp structural crossover line in the phase diagram. On one side of this
      line the common wavelength is approximately the diameter of the smaller sized
      spheres whereas on the other side it is approximately the diameter of the bigger
      ones; the wavelength of the longest ranged oscillations changes discontinuously
      at the structural crossover line. Using density functional theory and Monte Carlo
      simulations we show that structural crossover also manifests itself in the
      intermediate range behavior of the pair correlation functions and we comment on
      the relevance of this observation for real (colloidal) mixtures. In highly
      asymmetric mixtures, q< or =0.1, where there is metastable fluid-fluid
      transition, we find a Fisher-Widom line with two branches. This line separates a
      region of the phase diagram where the decay of pair correlations is oscillatory
      from one in which it is monotonic.

PMID- 15485250
TI  - Theoretical study of the local structure and Raman spectra of CaO-SiO2 binary
      melts.
AB  - A procedure for the Raman spectra calculation of vitreous and molten silicates
      was presented in this paper. It includes molecular dynamics MD simulation for the
      generation of equilibrium configurations, Wilson's GF matrix method for the
      calculations of eigenfrequencies and corresponding vectors, electro-optical
      parameters method (EOPM) for the Raman intensity calculations, and the bond
      polarizability model (BPM) for the determination of polarizability and
      polarizability derivative. One of the most important characteristics of this
      procedure is the achievement of the partial Raman spectra of five tetrahedral
      units, as well as the total spectral envelope. In this paper, the calculation was
      carried out for the vitreous and molten calcium silicates with different
      compositions and at various temperatures. It is worthwhile to note that the
      calculation is based on statistical configurations distribution in the space and
      so it is not needed to artificially adjust the full width at half maximum (FWHM)
      of spectra. It was also tested through the good agreement of the calculated
      spectra with the experimental, including some regularity of spectral properties.
      According to the calculation, the symmetrical stretching of whole tetrahedral
      units, to which the stretching of Si-O(nb) bond gives the main contribution to
      intensity, is proven to be the dominance in the high-frequency range (800-1200
      cm(-1)) and the symmetrical bending of Si-O(b)-Si, to which the stretching of Si
      O(b) bond exhibits the main contribution, is the dominance in the medium
      frequency range (400-700 cm(-1)). As the first theoretical results, the Raman
      scattering coefficient of each Q(i) was found little change along with the
      variation of composition and temperature.

PMID- 15485252
TI  - One-, two-, and three-photon absorption induced fluorescence of a novel
      chromophore in chloroform solution.
AB  - One-, two-, and three-photon absorption induced fluorescence intensities of a
      novel nonlinear optical chromophore have been measured by using a tunable
      femtosecond pulsed laser as the excitation. Four resonance peaks are observed as
      the excitation wavelength is tuned from 600 to 2000 nm. These peaks correspond to
      the one-, two- and three-photon fluorescence resonance. Except for intensity
      difference, the lifetime and the fluorescence spectrum are found to be the same
      for the one-, two-, or three-photon resonance, hence suggesting that the same
      excited energy level is involved in emitting the fluorescence intensity. A three
      level model is developed to account for the incident excitation laser intensity
      dependence of the one-photon and multiphoton fluorescence intensity. The model
      allows the multiphoton absorption cross sections to be extracted; it can also
      account for the deviation observed in the linear, square, and cubic intensity
      dependence of the one-, two-, and three-photon fluorescence intensity,
      respectively. To determine the absorption cross sections, the present method does
      not require the fluorescence quantum efficiency data, needed in the low intensity
      technique.

PMID- 15485251
TI  - Finite concentration effects on diffusion-controlled reactions.
AB  - The algorithm by Northrup, Allison, and McCammon [J. Chem. Phys. 80, 1517 (1984)]
      has been used for two decades for calculating the diffusion-influenced rate
      constants of enzymatic reactions. Although many interesting results have been
      obtained, the algorithm is based on the assumption that substrate-substrate
      interactions can be neglected. This approximation may not be valid when the
      concentration of the ligand is high. In this work, we constructed a simulation
      model that can take substrate-substrate interactions into account. We first
      validated the model by carrying out simulations in ways that could be compared to
      analytical theories. We then carried out simulations to examine the possible
      effects of substrate-substrate interactions on diffusion-controlled reaction
      rates. For a substrate concentration of 0.1 mM, we found that the diffusion
      controlled reaction rates were not sensitive to whether substrate-substrate
      interactions were included. On the other hand, we observed significant influence
      of substrate-substrate interactions on calculated reaction rates at a substrate
      concentration of 0.1M. Therefore, a simulation model that takes substrate
      substrate interactions into account is essential for reliably predicting
      diffusion-controlled reaction rates at high substrate concentrations, and one
      such simulation model is presented here.

PMID- 15485253
TI  - Libration induced stretching mode excitation for pump-probe spectroscopy in pure
      liquid water.
AB  - We developed an experimental approach to study pure liquid water in the infrared
      and avoid thermal effects. This technique is based on libration induced
      stretching excitation of water molecules. A direct correspondence between
      frequencies within the libration and OH stretching bands is demonstrated. Energy
      diffusion is studied in pure liquid water by measuring wave packet dynamics of OH
      stretching vibrator with infrared femtosecond spectroscopy. Wave packet dynamics
      reveals ultrafast energy dynamics and reflects 130 fs intermolecular energy
      transfer between water vibrators. Energy diffusion is almost two orders of
      magnitude faster than self diffusion in water.

PMID- 15485254
TI  - Single molecule photon emission statistics in the slow modulation limit.
AB  - A framework for calculating photon emission statistics for single chromophores
      perturbed by slow environmental fluctuations is introduced. When internal
      chromophore dynamics are significantly faster than time scales for environmental
      modulation it becomes possible to invoke a type of adiabatic approximation,
      allowing for straightforward calculation of photon counting moments including
      explicitly quantum effects. Unlike previous exact treatments, the present
      methodology involves calculation of dynamics reflecting only the modulation
      characteristics of the environment and quantum dynamics of an isolated
      chromophore separately, i.e., the complicated intermingling of chromophore
      quantum dynamics and the environmental modulation are suppressed via the
      adiabatic approximation. This leads to significant conceptual and computational
      simplifications. Within its regime of applicability, the present approximation
      reproduces exact calculations quantitatively. We demonstrate this accuracy
      explicitly for the case of a two-level chromophore modulated by a number of
      different stochastic models.

PMID- 15485255
TI  - Melting points and thermal expansivities of proton-disordered hexagonal ice with
      several model potentials.
AB  - A method of free energy calculation is proposed, which enables to cover a wide
      range of pressure and temperature. The free energies of proton-disordered
      hexagonal ice (ice Ih) and liquid water are calculated for the TIP4P [J. Chem.
      Phys. 79, 926 (1983)] model and the TIP5P [J. Chem. Phys. 112, 8910 (2000)]
      model. From the calculated free energy curves, we determine the melting point of
      the proton-disordered hexagonal ice at 0.1 MPa (atmospheric pressure), 50 MPa,
      100 MPa, and 200 MPa. The melting temperatures at atmospheric pressure for the
      TIP4P ice and the TIP5P ice are found to be about T(m)=229 K and T(m)=268 K,
      respectively. The melting temperatures decrease as the pressure is increased, a
      feature consistent with the pressure dependence of the melting point for
      realistic proton-disordered hexagonal ice. We also calculate the thermal
      expansivity of the model ices. Negative thermal expansivity is observed at the
      low temperature region for the TIP4P ice, but not for the TIP5P ice at the
      ambient pressure.

PMID- 15485256
TI  - Why hyperpolarizabilities fall short of the fundamental quantum limits.
AB  - Quantum sum rules impose limits on the hyperpolarizability, beta. A survey of the
      largest second-order molecular susceptibilities finds what appears to be a
      universal gap between the experimental results and the fundamental limits. In
      this work, we use theory, linear spectroscopy, Raman spectroscopy, and measured
      values of beta (using hyper-Rayleigh scattering and Stark Spectroscopy) to show
      that this gap is due to an unfavorable arrangement of excited state energies. The
      question of whether this result is a universal property of a quantum system or a
      matter of present paradigms for making molecules is discussed.

PMID- 15485257
TI  - Adsorption and dissociation of NO on stepped Pt (533).
AB  - We present an experimental and theoretical investigation of the adsorption,
      desorption, and dissociation of NO on the stepped Pt (533) surface. By combining
      temperature programmed desorption and reflection absorption infrared
      spectroscopy, information about the adsorption sites at different temperatures is
      obtained. Surprisingly, metastable adsorption structures of NO can be produced
      through variation of the dosing temperature. We also show that part of the NO
      molecules adsorbed on the step sites dissociates around 450 K. After dissociation
      the N atoms can desorb either by combining with an O fragment, or with another N
      atom, resulting in NO and N(2). The N(2) production can be enhanced by
      coadsorbing CO on the surface: CO scavenges the oxygen atom, thereby suppressing
      associative recombinative desorption of N and O atoms. Density functional theory
      calculations are used to reveal the adsorption energies and vibrational
      frequencies of adsorbed NO as well as barriers for dissociation of NO and for
      diffusion of N atoms. The combined experimental results and theoretical
      calculations reveal that dissociation of NO is the rate limiting step in the
      formation of N(2).

PMID- 15485258
TI  - Electric field and temperature effects on water in the narrow nonpolar pores of
      carbon nanotubes.
AB  - Water molecules in the narrow cylindrical pore of a (6,6) carbon nanotube form
      single-file chains with their dipoles collectively oriented either up or down
      along the tube axis. We study the interaction of such water chains with
      homogeneous electric fields for finite closed and infinite periodically
      replicated tubes. By evaluating the grand-canonical partition function term-by
      term, we show that homogeneous electric fields favor the filling of previously
      empty nanotubes with water from the bulk phase. A two-state description of the
      collective water dipole orientation in the nanotube provides an excellent
      approximation for the dependence of the water-chain polarization and the filling
      equilibrium on the electric field. The energy and entropy contributions to the
      free energy of filling the nanotube were determined from the temperature
      dependence of the occupancy probabilities. We find that the energy of transfer
      depends sensitively on the water-tube interaction potential, and that the entropy
      of one-dimensionally ordered water chains is comparable to that of bulk water. We
      also discuss implications for proton transfer reactions in biology.

PMID- 15485259
TI  - Competitive interaction between two different spherical sinks.
AB  - Competitive interactions within diverse mixed populations of chemically active
      sites are prevalent throughout nature, science, and engineering. Their effects
      are readily seen in the distribution of dead and surviving aerobic cells within a
      thick biofilm and particle shape changes during the growth and coarsening of
      crystals. Even in the most dilute case, competition for a reactant requires at
      least two spheres/cells, and the solution of the two-spherical sink problem is of
      interest for several reasons. The solution accurately describes lower cell
      concentration behavior (10(8) cells/l), and like the Smoluchowski diffusion
      reaction treatment for a single sphere, the analysis is extremely helpful in
      understanding the fundamental phenomena of the effect on the first spherical sink
      of the presence of a second different spherical sink. In addition these exact
      solutions are required for the systematic extension to higher density behavior by
      rigorous expansions in the spherical sink densities. The method of the twin
      spherical expansion is used with a formal matrix elimination scheme to generate
      an exact solution for two distinct spherical sinks of differing sizes and
      kinetics. The two sinks exist in a medium, which supplies a reactant to the sinks
      via Fickian diffusion. The two sinks compete for the same reactant with different
      first-order reactions occurring at the surface of each sink. Earlier work focused
      on two spherical sinks of the same size with identical surface reaction kinetics.
      This work has been advanced to allow for diversity in the theory of cellular or
      reactive sink competition. A number of interesting higher order interactive
      phenomena are observed in this paper when the different reactive sinks are in
      close proximity. (c) 2004 American Institute of Physics.

PMID- 15485260
TI  - Raman-scattering elucidation of the giant isotope effect in hydrogen-ion
      blistering of silicon.
AB  - In this work, we investigate the origin of a giant isotope effect discovered in
      the blistering of hydrogen-ion-implanted and annealed silicon. Si(001) samples
      were implanted or co-implanted with 5 keV of H and/or D ions to total fluences of
      2 x 10(16) and 6 x 10(16) ion/cm(2). The lower fluence is sufficient for
      blistering by pure H, but the higher one is required for the maximum blister
      coverage whenever D is involved. On these samples, we carried out Raman
      scattering investigations of the evolution of Si-H/D complexes upon a stepwise
      thermal annealing from 200 to 550 degrees C. We have identified the critical
      chemical transformations characterizing the hydrogen-deuterium-induced blistering
      of silicon. The puzzling dependence on ion mass appears to be mainly connected
      with the nature of the radiation damage. We have found that H is more efficient
      in "preparing the ground" for blistering by nucleating platelets parallel to the
      surface, essentially due to its ability to agglomerate in the multihydride
      monovacancy complexes that evolve into hydrogenated extended internal surfaces.
      By contrast, D is preferentially trapped in the surprisingly stable monodeuteride
      multivacancies.

PMID- 15485261
TI  - Lattice-Boltzmann simulation of coalescence-driven island coarsening.
AB  - A two-dimensional lattice-Boltzmann model (LBM) with fluid-fluid interactions was
      used to simulate first-order phase separation in a thin fluid film. The
      intermediate asymptotic time dependence of the mean island size, island number
      concentration, and polydispersity were determined and compared with the
      predictions of the distribution-kinetics model. The comparison revealed that the
      combined effects of growth, coalescence, and Ostwald ripening control the phase
      transition process in the LBM simulations. However, the overall process is
      dominated by coalescence, which is independent of island mass. As the phase
      transition advances, the mean island size increases, the number of islands
      decrease, and the polydispersity approaches unity, which conforms to the
      predictions of the distribution-kinetics model. The effects of the domain size on
      the intermediate asymptotic island size distribution, scaling form of the island
      size distribution, and the crossover to the long-term asymptotic behavior were
      elucidated.

PMID- 15485262
TI  - Equilibrium and kinetics: water confined in carbon nanotubes as one-dimensional
      lattice gas.
AB  - We present a simple one-dimensional lattice gas model, which describes very well
      the equilibrium and kinetic behaviors of water confined in a thin carbon nanotube
      found in an atomistic molecular dynamics simulation [G. Hummer, J. C. Rasaiah,
      and J. P. Noworyta, Nature (London), 414, 188 (2001)]. The model parameters
      correspond to various physical interactions and can be calculated or estimated by
      using statistical mechanics. Then, the roles of all interactions in the water
      filling, emptying, and transporting processes are clearly understood. Our results
      indicate that the interaction from the water molecules outside the nanotube plays
      a key role in these processes and the interaction can be simply treated as an
      average effect of the bulk water.

PMID- 15485263
TI  - Temperature dependence of the structure of Langmuir films of normal-alkanes on
      liquid mercury.
AB  - The temperature dependent phase behavior of Langmuir films of n-alkanes
      [CH3(CH2)(n-2)CH3, denote Cn] on mercury was studied for chain lengths 19< or =n<
      or =22 and temperatures 15< or =T< or =44 degrees C, using surface tensiometry
      and surface x-ray diffraction methods. In contrast with Langmuir films on water,
      where molecules invariably orient roughly surface normal, alkanes on mercury are
      always oriented surface parallel and show no long-range in-plane order at any
      surface pressure. A gas and several condensed phases of single, double, and
      triple layers of lying-down molecules are found, depending on n and T. At high
      coverages, the alkanes studied here show transitions from a triple to a double to
      a single layer with increasing temperature. The transition temperature from a
      double to a single layer is found to be approximately 5 degrees C, lower than the
      bulk rotator-to-liquid melting temperature, while the transition from a triple to
      a double layer is about as much below the double-to-single layer transition. Both
      monolayer and bulk transition temperatures show a linear increase with n with
      identical slopes of approximately 4.5 degrees C/CH2 within the range of n values
      addressed here. It is suggested that the film and bulk transitions are both
      driven by a common cause: the proliferation of gauche defects in the chain with
      increasing temperature.

PMID- 15485264
TI  - Self-directed growth of benzonitrile line on H-terminated Si(001) surface.
AB  - Using first-principles density-functional calculations we predict a self-directed
      growth of benzonitrile molecular line on a H-terminated Si(001) surface. The
      C[triple bond]N bond of benzonitrile reacts with a single Si dangling bond which
      can be generated by the removal of a H atom, forming one Si-N bond and one C
      radical. Subsequently, the produced C radical can be stabilized by abstracting a
      H atom from a neighboring Si dimer, creating another H-empty site. This H
      abstraction process whose activation barrier is 0.65 eV sets off a chain reaction
      to grow one-dimensional benzonitrile line along the Si dimer row. Our calculated
      energy profile for formation of the benzonitrile line shows its relatively easier
      formation compared with previously reported styrene and vinylferrocene lines.

PMID- 15485266
TI  - Nucleation in cylindrical capillaries.
AB  - We use a local density functional theory in the square gradient approximation to
      explore the properties of critical nuclei for the liquid-vapor transition of van
      der Waals fluids in cylindrical capillaries. The proposed model allows us to
      investigate the effect of pore size, surface field, and supersaturation on the
      behavior of the system. Our calculations predict the existence of at least three
      different pathways for the nucleation of droplets and bubbles in these confined
      fluids: axisymmetric annular bumps and lenses, and asymmetric droplets. The
      morphological transition between these different structures is driven by the
      existence of states of zero compressibility in the capillary. We show that the
      classical capillarity theory provides surprisingly accurate predictions for the
      work of formation of critical nuclei in cylindrical pores when line tension
      contributions to the free energy are taken into account.

PMID- 15485265
TI  - Simulations of stable pores in membranes: system size dependence and line
      tension.
AB  - Amphiphilic bilayers with a pore were simulated using a coarse grained model. By
      stretching the bilayer to 70% beyond its equilibrium surface area, we established
      the phase diagram of pores, identifying regions where pores are stable,
      metastable, or unstable. A simple theoretical model is proposed to explain the
      phase diagram, and to calculate the critical and equilibrium relative stretches.
      Interestingly, these are found to scale with the inverse cubic root of the number
      of amphiphiles in the bilayer, thus explaining the order of magnitude difference
      between the simulated and the measured values. Three different methods are used
      to calculate a line tension coefficient of (3.5-4.0) x 10(-11) J/m, in good
      agreement with experimental data.

PMID- 15485267
TI  - Hybrid atomistic-coarse-grained treatment of thin-film lubrication. II.
AB  - A new hybrid atomistic-coarse-grained (HACG) treatment of reversible processes in
      multiple-scale systems involving fluid-solid interfaces was tested through
      isothermal-isobaric Monte Carlo simulations of the quasistatic shearing of a
      model two-dimensional lubricated contact comprising two planar Lennard-Jones
      solid substrates that sandwich a softer Lennard-Jones film. Shear-stress profiles
      (plots of shear stress T(yx) versus lateral displacement of the substrates)
      obtained by the HACG technique, which combines an atomistic description of the
      interfacial region with a continuum description of regions well removed from the
      interface, are compared with "exact" profiles (obtained by treating the whole
      system at the atomic scale) for a selection of thermodynamic states that
      correspond to systematic variations of temperature, load (normal stress), film
      substrate coupling strength, and film thickness. The HACG profiles are in
      excellent agreement overall with the exact ones. The HACG scheme provides a
      reliable description of quasistatic shearing under a wide range of conditions. It
      is demonstrated that the elastic response of the remote regions of the substrates
      can have a significant impact on the static friction profile (plot of maximum
      magnitude of T(yx) versus load).

PMID- 15485268
TI  - Laser pulse control of ultrafast heterogeneous electron transfer: a computational
      study.
AB  - Laser pulse control of the photoinduced 90 fs charge injection from perylene into
      the conduction band of TiO2 is studied theoretically. The approach accounts for
      the electronic-ground state of the dye, the first excited state, the ionized
      state formed after charge injection, and the continuum of the electronic states
      in the conduction band, all defined vs a single reaction coordinate. To address
      different control tasks optimal control theory is combined with a full quantum
      dynamical description of the electron-vibrational motion accompanying the charge
      injection process. First it is proved in which way the charge injection time can
      be changed by tailored laser pulses. In a second step a pump-dump scheme from the
      perylene ground state to the first excited electronic state and back to the
      ground state is discussed. Because of the strong coupling of the excited perylene
      state to the band continuum of TiO2 this control task is more suited to an
      experimental test than the direct control of the charge injection.

PMID- 15485269
TI  - Green's function formalism coupled with Gaussian broadening of discrete states
      for quantum transport: application to atomic and molecular wires.
AB  - A Green's function formalism incorporating broadened density of states (DOS) is
      proposed for the calculation of electrical conductance. In cluster-molecule
      cluster systems, broadened DOS of the clusters are defined as continuous DOS of
      electrodes and used to calculate Green's function of electrodes. This approach
      combined with density functional theory is applied to the electrical transmission
      of gold atomic wires and molecular wires consisting of benzene-1,4-dithiolate,
      benzene-1,4-dimethanethiolate, 4,4(')-bipyridine, hexane dithiolate, and octane
      dithiolate. The B3LYP, B3PW91, MPW1PW91, SVWN, and BPW91 functionals with the
      LANL2DZ, CEP, and SDD basis sets are employed in the calculation of conductance.
      The width parameter was successfully determined to reproduce the quantum unit of
      conductance 2e(2)/h in gold atomic wires. The combination of the B3LYP hybrid
      functional and the CEP-31G basis set is excellent in reproducing measured
      conductances of molecular wires by Tao et al. [Science 301, 1221 (2003); J. Am.
      Chem. Soc. 125, 16164 (2003); Nano Lett. 4, 267 (2004)].

PMID- 15485270
TI  - Molecular beam investigation of hydrogen dissociation on Si(001) and Si(111)
      surfaces.
AB  - The influence of molecular vibrations on the reaction dynamics of H2 on Si(001)
      as well as isotopic effects have been investigated by means of optical second
      harmonic generation and molecular beam techniques. Enhanced dissociation of
      vibrationally excited H2 on Si(001)2 x 1 has been found corresponding to a
      reduction of the mean adsorption barrier to 390 meV and 180 meV for nu=1 and
      nu=2, respectively. The adsorption dynamics of the isotopes H2 and D2 show only
      small differences in the accessible range of beam energies between 50 meV and 350
      meV. They are traced back to different degrees of vibrational excitation and do
      not point to an important influence of quantum tunneling in crossing the
      adsorption barrier. The sticking probability of H2 on the 7 x 7-reconstructed
      Si(111) surface was found to be activated both by H2 kinetic energy and surface
      temperature in a qualitatively similar fashion as H2/Si(001)2 x 1.
      Quantitatively, the overall sticking probabilities of H2 on the Si(111) surface
      are about one order of magnitude lower than on Si(001), the influence of surface
      temperature is generally stronger.

PMID- 15485271
TI  - Tacticity effects on the barriers to rotation of the ester methyl group in poly
      (methyl methacrylate): a deuteron magnetic resonance study.
AB  - In isotactic poly(methyl methacrylate) (PMMA), we investigate the dynamics of the
      ester methyl groups by means of deuteron magnetic resonance (DMR) in a deuterated
      sample. We find that the motion of the CD(3)-group affects the deuteron spin
      lattice relaxation as well as the DMR line shape in a characteristic way.
      Quadrupolar order spin lattice relaxation measurements between T=291 K and T=70 K
      reveal a broad temperature dependent probability distribution of autocorrelation
      times tau(c) for the 2pi/3 reorientation. This broad distribution corresponds to
      a temperature independent Gaussian distribution of activation energies rho(E(a))
      with variance sigma(E(a) )=13.8+/-0.5 meV (1.33 kJ/mol). The line shape
      transition between T=70 K and T=23 K is explained with the freezing in of the
      methyl group reorientation. By comparing our results in an 88% isotactic sample
      with results obtained from a 50% syndiotactic, 30% atactic, and 20% isotactic
      sample of a previous investigation, we demonstrate the higher local order of the
      88% isotactic sample, which corresponds to a ratio of 1.6 in the relative width
      sigma(E(a) )/E(a) of the E(a) distribution. We show that different stereospecific
      forms of PMMA can be easily distinguished by the characteristics of their line
      shape transition between T=70 K and T=23 K.

PMID- 15485272
TI  - Molecular theory of dielectric relaxation in nematic dimers.
AB  - This paper reports a theory for the dielectric relaxation of dimeric mesogenic
      molecules in a nematic liquid crystal phase. Liquid crystal dimers consist of two
      mesogenic groups linked by a flexible chain. Recent experimental studies [D. A.
      Dunmur, G. R. Luckhurst, M. R. de la Fuente, S. Diez, and M. A. Perez Jubindo, J.
      Chem. Phys. 115, 8681 (2001)] of the dielectric properties of polar liquid
      crystal dimers have found unexpected results for both the static (low frequency)
      and variable frequency dielectric response of these materials. The theory
      developed in this paper provides a quantitative model with which to understand
      the observed experimental results. The mean-square dipole moments of alpha,omega
      bis[(4-cyanobiphenyl-4'-yl]alkanes in a nematic phase have been calculated using
      both the rotational isomeric state model and a full torsional potential for the
      carbon-carbon bonds of the flexible chain. The orienting effect of the nematic
      phase is taken into account by a parametrized potential of mean torque acting on
      the mesogenic groups and the segments in the flexible chain. Results of
      calculations using the full torsional potential are in excellent agreement with
      experimental results for comparable systems. The probability density
      p(eq)(beta(A),beta(B)) for the orientation of the mesogenic groups (A,B) along
      the nematic director is also calculated. The resultant potential of mean torque
      is a surface characterized by four deep energy wells or sites equivalent to
      alignment of the terminal groups A and B approximately parallel and antiparallel
      to the director; of course, the reversal of the director leads to equivalent
      sites. This potential energy surface provides the basis for a kinetic model of
      dielectric relaxation in nematic dimers. Solution of the Fokker-Planck equation
      corresponding to this four-site model gives the time dependence of the site
      populations, and hence the time-correlation functions for the total dipole moment
      along the director. In this model the end-over-end rotation of the molecule,
      corresponding to simultaneous reversal of both mesogenic groups, is excluded
      because the activation energy is too large. Results are presented for a number of
      cases, in which a dipole is located on one or both of the mesogenic groups, and
      additionally where the groups differ in size. For the latter, under particular
      conditions, the correlation function exhibits a biexponential decay, which
      corresponds to two low frequency absorptions in the dielectric spectrum. This is
      exactly what has been observed for nonsymmetric nematic dimers having different
      groups terminating a flexible chain. Experimental results over a range of
      temperature for the nonsymmetric dimer alpha-[(4-cyanobiphenyl)-4'-yloxy]-omega
      (4-decylanilinebenzylidene-4'-oxy)nonane can be fitted precisely to the theory,
      which provides new insight into the orientational and conformational dynamics of
      molecules in ordered liquid crystalline phases.

PMID- 15485273
TI  - Kinetics of polymer translocation through a pore.
AB  - We theoretically study kinetics of a polymer threading through a pore embedded in
      a flat membrane. We numerically solve three coupled kinetic equations for the
      number n(1) of polymer segments in one side of the membrane and expansion factors
      of the polymer chain in each side of the membrane. We find the time evolution
      n(1) proportional to t(1/(1+nu)) at late stages and the translocation time tau(t)
      is scaled as tau(t) proportional to 1+nu) for large number n of the polymer
      segments, where nu is the effective size exponent of the radius of gyration of
      the polymer. When the polymer is translocated into a region with a good solvent
      condition (nu=3/5), we obtain n(1) proportional to t(5/8) and tau(t) proportional
      to n(8/5).

PMID- 15485274
TI  - Transcription-driven twin supercoiling of a DNA loop: a Brownian dynamics study.
AB  - The torque generated by RNA polymerase as it tracks along double-stranded DNA can
      potentially induce long-range structural deformations integral to mechanisms of
      biological significance in both prokaryotes and eukaryotes. In this paper, we
      introduce a dynamic computer model for investigating this phenomenon. Duplex DNA
      is represented as a chain of hydrodynamic beads interacting through potentials of
      linearly elastic stretching, bending, and twisting, as well as excluded volume.
      The chain, linear when relaxed, is looped to form two open but topologically
      constrained subdomains. This permits the dynamic introduction of torsional stress
      via a centrally applied torque. We simulate by Brownian dynamics the 100 micros
      response of a 477-base pair B-DNA template to the localized torque generated by
      the prokaryotic transcription ensemble. Following a sharp rise at early times,
      the distributed twist assumes a nearly constant value in both subdomains, and a
      succession of supercoiling deformations occurs as superhelical stress is
      increasingly partitioned to writhe. The magnitude of writhe surpasses that of
      twist before also leveling off when the structure reaches mechanical equilibrium
      with the torsional load. Superhelicity is simultaneously right handed in one
      subdomain and left handed in the other, as predicted by the "transcription
      induced twin-supercoiled-domain" model [L. F. Liu and J. C. Wang, Proc. Natl.
      Acad. Sci. U.S.A. 84, 7024 (1987)]. The properties of the chain at the onset of
      writhing agree well with predictions from theory, and the generated stress is
      ample for driving secondary structural transitions in physiological DNA.

PMID- 15485275
TI  - Importance of chain-chain interactions on the band gap of trans-polyacetylene as
      predicted by second-order perturbation theory.
AB  - We employ the Laplace-transformed second-order Moller-Plesset perturbation theory
      for periodic systems in its atomic orbital basis formulation to determine the
      geometric structure and band gap of interacting polyacetylene chains. We have
      studied single, double, and triple chains, and also two-dimensional crystals. We
      estimate from first principles the equilibrium interchain distance and setting
      angle, along with binding energy between trans-polyacetylene chains due to
      dispersion interactions. The dependence of the correlation corrected
      quasiparticle band gap on the intrachain and interchain geometric parameters is
      studied, obtaining that the gap of the compound structures is substantially
      reduced with respect to the single chain polymer.

PMID- 15485276
TI  - Self-consistent mode-coupling theory for the viscosity of rodlike polyelectrolyte
      solutions.
AB  - A self-consistent mode-coupling theory is presented for the viscosity of
      solutions of charged rodlike polymers. The static structure factor used in the
      theory is obtained from polymer integral equation theory; the Debye-Huckel
      approximation is inadequate even at low concentrations. The theory predicts a
      nonmonotonic dependence of the reduced excess viscosity eta(R) on concentration
      from the behavior of the static structure factor in polyelectrolyte solutions.
      The theory predicts that the peak in eta(R) occurs at concentrations slightly
      lower than the overlap threshold concentration, c*. The peak height increases
      dramatically with increasing molecular weight and decreases with increased
      concentrations of added salt. The position of the peak, as a function of
      concentration divided by c*, is independent of salt concentration or molecular
      weight. The predictions can be tested experimentally.

PMID- 15485277
TI  - Equation of state and liquid-vapor equilibria of one- and two-Yukawa hard-sphere
      chain fluids: theory and simulation.
AB  - The accuracy of several theories for the thermodynamic properties of the Yukawa
      hard-sphere chain fluid are studied. In particular, we consider the polymer mean
      spherical approximation (PMSA), the dimer version of thermodynamic perturbation
      theory (TPTD), and the statistical associating fluid theory for potentials of
      variable attractive range (SAFT-VR). Since the original version of SAFT-VR for
      Yukawa fluids is restricted to the case of one-Yukawa tail, we have extended SAFT
      VR to treat chain fluids with two-Yukawa tails. The predictions of these theories
      are compared with Monte Carlo (MC) simulation data for the pressure and phase
      behavior of the chain fluid of different length with one- and two-Yukawa tails.
      We find that overall the PMSA and TPTD give more accurate predictions than SAFT
      VR, and that the PMSA is slightly more accurate than TPTD.

PMID- 15485278
TI  - Structure and rheological behavior of casein micelle suspensions during
      ultrafiltration process.
AB  - The stability and mechanism underlying the formation of deposits of casein
      micelles during ultrafiltration process were investigated by small-angle and
      ultra small-angle x-ray scattering (SAXS and USAXS). The casein micelle
      dispersions consisted of phospho-caseinate model powders and the measurements
      probed length scales ranging from 1 to 2000 nm. Rheometric and frontal filtration
      measurements were combined with SAXS to establish the relationship between the
      rheological behavior of deposits (shear and/or compression) and the corresponding
      microstructure. The results revealed two characteristic length scales for the
      equilibrium structure with radius of gyrations R(g), about 100 and 5.6 nm
      pertaining to the globular micelles and their non-globular internal structure,
      respectively. The SAXS measurements further indicated that the increase of
      temperature from 20 to 70 degrees C or the decrease of pH from 6.6 to 6 lead to
      agglomeration of the globular micelles. In situ scattering measurements showed
      that the decrease of permeation flows is directly related to the deformation and
      compression of the micelles in the immediate vicinity of the membrane.

PMID- 15485279
TI  - A reactive force field simulation of liquid-liquid phase transitions in
      phosphorus.
AB  - A force field model of phosphorus has been developed based on density functional
      (DF) computations and experimental results, covering low energy forms of local
      tetrahedral symmetry and more compact (simple cubic) structures that arise with
      increasing pressure. Rules tailored to DF data for the addition, deletion, and
      exchange of covalent bonds allow the system to adapt the bonding configuration to
      the thermodynamic state. Monte Carlo simulations in the N-P-T ensemble show that
      the molecular (P(4)) liquid phase, stable at low pressure P and relatively low
      temperature T, transforms to a polymeric (gel) state on increasing either P or T.
      These phase changes are observed in recent experiments at similar thermodynamic
      conditions, as shown by the close agreement of computed and measured structure
      factors in the molecular and polymer phases. The polymeric phase obtained by
      increasing pressure has a dominant simple cubic character, while the polymer
      obtained by raising T at moderate pressure is tetrahedral. Comparison with DF
      results suggests that the latter is a semiconductor, while the cubic form is
      metallic. The simulations show that the T-induced polymerization is due to the
      entropy of the configuration of covalent bonds, as in the polymerization
      transition in sulfur. The transition observed with increasing P is the
      continuation at high T of the black P to arsenic (A17) structure observed in the
      solid state, and also corresponds to a semiconductor to metal transition.

PMID- 15485280
TI  - Chain conformation in two-dimensional dense state.
AB  - In an effort to provide evidence concerning the conformation of many chains in
      strict two-dimensional (2D) dense state, we synthesized polymer chains of
      diameter of nanometers through an anionic polymerization process. The
      conformational characteristics of the long chain molecules in films of thickness
      h corresponding to the chain diameter a were directly obtained from atomic force
      microscopy observations. In 2D dispersed state, the conformations of the long
      chain molecules were typical Gaussian. However, in 2D dense state the long chain
      molecules were strongly interpenetrated. Their conformations were largely
      perturbed by the presence of neighbor chains and were not Gaussian. This result
      was in contradiction with the segregated globule model predicted by de Gennes.
      The central reason is that 2D space cannot be filled to normal density with 2D
      Gaussian globules; either the area must be greatly increased with consequently
      large voids, or the globule conformation must be expanded by allowing chains to
      interpenetrate each other.

PMID- 15485281
TI  - Comment on "Postnucleation droplet growth in supersaturated gas with arbitrary
      vapor concentration" [J. Chem. Phys. 120, 10455 (2004)].
AB  - We provide the overview of the papers dealing with the growth of the liquid
      droplet. The purpose is to put the paper "Postnucleation droplet growth in
      supersaturated gas with arbitrary vapor concentration" [V. Pines, M. Zlatkowski,
      and A. Chait, J. Chem. Phys. 120, 10455 (2004)] in the right historical context.
      The original paper and this comment point the correct condensation formula to the
      atmospheric science community.

PMID- 15485283
TI  - An approach to understanding the transmission of Mycobacterium leprae using
      molecular and immunological methods: results from the MILEP2 study.
AB  - BACKGROUND: The current strategy for leprosy control using case detection and
      treatment has greatly reduced the prevalence of leprosy, but has had no
      demonstrable effect on interrupting transmission. METHODS: Three leprosy endemic
      communities in India were recruited, examined, and followed up sequentially over
      2 yrs using nasal swabs and saliva collections. The nasal swabs were tested by
      polymerase chain reaction for the presence of M. leprae and the saliva was
      assayed for anti-M. leprae IgA. FINDINGS: Only 1.6% of 2552 nasal swabs were PCR
      positive, and 68% of saliva samples were positive for ML-IgA. BCG and household
      contact status was associated with the mucosal immune response, but not with PCR
      positivity. PCR positivity did not persist and most PCR positive results were in
      the wet season. INTERPRETATION: The findings contribute to our understanding of
      the epidemiology of M. leprae and the possible periods of greatest likelihood of
      exposure and transmission.

PMID- 15485284
TI  - Validity of the WHO operational classification and value of other clinical signs
      in the classification of leprosy.
AB  - The objective of this study is to examine the validity of the WHO operational
      classification using skin smear results as the gold standard and explore the
      value of additional clinical signs independently and in combination with the WHO
      classification. Between 1985 and 2000, 5439 new untreated leprosy patients were
      registered at the Schieffelin Leprosy Research and Training Center, Karigiri.
      They were classified according to the Ridley Jopling classification as well as
      WHO operational classification based on the number of skin lesions. The
      sensitivity and specificity of the WHO operational classification tested, using
      skin smear results as the gold standard, was found to be 88.6% and 86.7%
      respectively. The Receiver Operator Characteristic (ROC) curve confirms that the
      best option for sensitivity and specificity is a cut off of 6 and more lesions
      for MB. The validity of the number of enlarged nerves and size of the largest
      skin lesion as independent criteria to classify patients was found to be poor.
      Addition of three enlarged trunk nerves to the WHO classification improved its
      sensitivity to 91.4%, while the specificity remained almost unchanged at 85.3%.
      Addition of the size of the largest skin lesion to the WHO classification reduced
      its validity considerably. The study concludes that the WHO recommendation of
      using six and more lesions for classifying a patient as MB is the best option
      available at the moment, and calls for further research to identify other
      clinical criteria that have a better validity and could be easily applied in the
      field.

PMID- 15485285
TI  - Pure neuritic leprosy in India: an appraisal.
AB  - BACKGROUND: Pure neuritic leprosy (PNL) constitutes a significant proportion of
      all cases in India, however, this form of disease has not been fully recognized
      and investigated and there is little information in the existing literature.
      OBJECTIVE: To study the epidemiological characteristics of PNL in India.
      MATERIALS AND METHODS: A retrospective analysis of leprosy clinic records for the
      period 1993 to 2003 was undertaken. Detailed demographic profiles and clinical
      findings were noted from the predesigned clinic proforma. A slit-skin smear for
      acid-fast baclli (AFB) was done in all cases from the area of sensory loss. A
      skin biopsy was done from the area of sensory impairment to study
      histopathological changes. Further investigations such as nerve conduction
      velocity studies (NCV), fine needle aspiration cytology (FNAC), or nerve biopsy
      (superficial nerve twigs) were done if indicated in patients whenever there was
      difficulty in clinical diagnosis. RESULTS: Of the total 1542 leprosy patients
      seen over this period, 65 (4.2%) had PNL. Males were more commonly affected than
      females (2.6:1.). The majority of patients 40/65(61.5%) were aged between 15 and
      35 yrs. Predominant presenting symptoms were paresthesia, pain, sensory/motor
      deficit, and trophic changes. A majority of the patients 39/65 (60.0%) presented
      with involvement of 2 or more nerves in the same extremity. Mononeuritis was seen
      in 26 (40%) patients. The nerves most often involved were the right ulnar nerve
      in the upper extremity, and the right common peroneal nerve in the lower limb. In
      general, the nerves of the upper extremity were more commonly involved than in
      the lower limbs (67 vs. 55). Motor deformities such as claw hand and foot drop
      were present in 13/75 (20%) and 7/65 (10.8%) patients, respectively. Slit-skin
      smears were negative in all patients, and skin histopathology from the area of
      sensory loss revealed non-specific inflammation in the dermis in a majority of
      patients, with perineural inflammation in a few. All patients were treated with
      multi-drug therapy (MDT); patients with >/=2 peripheral nerve trunk involvements
      were treated with WHO MDT MB regimen, while others were administered WHO MDT PB
      regimen. Follow-up for up to 2 yrs was available in only 32/65 (49.2%) patients,
      none of whom developed any skin lesions during this period. CONCLUSION: PNL is a
      distinct subset of disease frequently seen in India. There is need to pay more
      attention to this form of leprosy and diagnose and treat patients earlier to
      prevent deformities and sequelae of nerve damage.

PMID- 15485286
TI  - "Tap sign" in tuberculoid and borderline tuberculoid leprosy.
AB  - Deep pain upon percussion of lesions over bone in tuberculoid leprosy, in spite
      of superficial sensory impairment, has been described as the "Tap Sign" (TS).
      This study was conducted to identify possible causes for this phenomenon and to
      determine the sensitivity and specificity of this sign in leprosy patients with
      lesions overlying bone. In 37/53 patients with lesions over bone, the sensitivity
      of the TS was 66.7% and the specificity was 100%. The positive predictive value
      was 100%, and the negative predictive value was 75%. The Tap Sign appears to be a
      useful clinical sign in diagnosis of tuberculoid and borderline tuberculoid
      leprosy where a lesion overlies a bone (sensitivity 66.7%). This test could be
      very useful to increase the clinical diagnostic yield, in the global perspective,
      in places where leprosy is diagnosed and treated by healthcare workers and
      primary care physicians without other laboratory facilities. Possible mechanisms
      responsible for the deep pain are discussed.

PMID- 15485287
TI  - In situ hybridization in the histological diagnosis of early and clinically
      suspect leprosy.
AB  - The present study tests the utility of the in situ hybridization procedure for M.
      leprae rRNA in the histological diagnosis of early leprosy and clinically suspect
      leprosy, both diagnostically demanding situations. The histological confirmation
      obtained with routine histopathology (Haematoxylin-Eosin staining for studying
      morphologic alterations and Fite-Faraco staining for demonstration of acid-fast
      bacilli) were 32% for early leprosy and 25% for clinically suspect leprosy. With
      performance of the in situ hybridization on the histologically unconfirmed cases,
      the positivity rates obtained were 58.8% and 55%, respectively. The results of
      the study confirm the utility of the procedure in the diagnostically difficult
      situations of early and suspect leprosy, and it is proposed that the procedure be
      employed in situations of clinical doubt.

PMID- 15485288
TI  - Nineteenth century Indian leper censuses and the doctors.
AB  - This study describes the circumstances under which enumerations of "lepers" were
      conducted in India in the late 19th century, and the ideological biases of the
      respective investigators and the meanings that they read into the statistics.
      This report focuses on the Bombay Presidency leprosy returns of 1867, examined in
      1871 by Henry Vandyke Carter, and the decennial nation-wide population census of
      1871-1872, 1881, and 1891, in which the leprosy-affected, among other infirm
      persons, were also enumerated. The evidence examined includes the investigators'
      reports and other published and unpublished contemporaneous documents. These
      censuses were undertaken at a time when the etiology of leprosy was a major
      controversy, but the evidence here indicates that the efforts to clarify the
      etiology and estimate the virulence of the disease in India by means of
      statistics were animated by the desire to justify and embellish pre-conceptions.
      Despite the claim that they were necessary for leprosy control, the censuses, for
      various reasons, were not utilized towards that end in India.

PMID- 15485289
TI  - Commentary: is it really M. leprae?

PMID- 15485290
TI  - A comparative study between 12 and 24-dose therapeutic regimens for
      multibacillary leprosy patients.
AB  - A comparative study was made of the initial and final bacterial indices (BIs) of
      213 MB leprosy patients who had been administered 12-dose (Group 1/128 patients)
      and 24-dose (Group 2/85 patients) World Health Organization multi-drug therapy to
      measure the effectiveness of both treatment regimens. All patients were evaluated
      at the beginning of treatment, at 12 months, and again after 24 months had
      elapsed. Decline in BI values and average BIs at 24 months were found to be
      similar for both groups. Moreover, no statistical difference between the two
      treatment regimens was found in the frequency rate of reaction.

PMID- 15485291
TI  - False positive reaction of the immunohistochemistry technique using anti-BCG
      polyclonal antibodies to identify Mycobacterium leprae in wild nine-banded
      armadillos.
AB  - The authors studied 66 wild nine-banded armadillos from Brazil. The ear samples
      were collected and Ziehl-Neelsen or Fite-Faraco stains were performed, as well as
      immunostaining using polyclonal BCG antibody, to avaluate the presence of the
      Mycobacterium leprae. The AFB were not detected by the Ziehl-Neelsen or Fite
      Faraco staining, neither immunoexpression of the BCG marker. However, many normal
      structures from the ears of the nine-banded armadillos, such as condrocytes,
      condroblasts, fibroblasts and endothelial cells, and Gram positive bacteria
      cocci, showed false positive reaction by the BCG marker. The authors discuss the
      use of the immunohistochemical studies with the polyclonal BCG antibody to
      identify M. leprae antigens in wild armadillos.

PMID- 15485298
TI  - The endangered health system: a progress report on workforce and work environment
      issues.

PMID- 15485299
TI  - Health care's human crisis - RX for an evolving profession.
AB  - In 2001, the Robert Wood Johnson Foundation commissioned a study on the nursing
      shortage in the United States to gain a better understanding of the drivers and
      inform the Foundation's response. This article discusses the impetus for, and a
      brief summary of, the resulting report, "Health Care's Human Crisis: The American
      Nursing Shortage," published by the Foundation in 2002. It examines the
      historical, social, cultural, and economic factors that drive the nursing
      shortage. A new framework, namely a continuum of responses, is offered for
      understanding the myriad activities being undertaken in response to the problem,
      pointing the way to long-term, sustainable solutions. Recommendations and
      implications for nursing leaders are discussed.

PMID- 15485300
TI  - The American Health Care system at a crossroads: an overview of the American
      Organization of Nurse Executives monograph.
AB  - The current nursing shortage is expected to worsen in the coming decades as the
      average age of working RNs rises and more RNs reach retirement age. The American
      Organization of Nurse Executives (AONE) has published a monograph, "Perspectives
      on the Nursing Shortage: A Blueprint for Action," which discusses factors
      contributing to the current shortage and outlines steps that must be taken to
      ensure a nursing workforce to meet future demand. In this article, the author
      summarizes key elements of the AONE monograph, including the factors that
      contributed to the writing of this monograph, recommendations for resolving the
      current and impending nursing shortfall, and actions that practicing nurses can
      take to help ensure a robust workforce for the future.

PMID- 15485301
TI  - Nursing in the next decade: implications for health care and for patient safety.
AB  - Nursing faces yet another divergence between demand and supply that is evidenced
      in insufficient nurse staffing with significant implications for patient safety.
      Many believe this shortage of registered nurses is entrenched in long-standing
      problems related to the value and image of nursing and the limited role nursing
      has had in identifying priorities within health care delivery systems. "Nursing's
      Agenda for the Future" is a plan resulting from the experience and wisdom of a
      broad representation of general nursing and nursing specialty organizations.
      Efforts to realize the priorities and objectives have evolved over the past two
      years in order to make larger strides, or quantum leaps, toward reaching the
      objectives contained within the plan. This article reviews the activities leading
      up to the development of this plan, presents the key areas of concern addressed
      in this plan, describes what has been accomplished since the publication of this
      plan in 2002, and outlines the work that lies ahead to bring to fruition the
      objectives the plan established.

PMID- 15485302
TI  - Dissipating the perfect storm - responses from nursing and the health care
      industry to protect the public's health.
AB  - This article summarizes the major national workforce reports and references the
      need for a tiered and comprehensive approach to avert the imminent nursing
      shortage crisis. Since 2002, commendable efforts have been made to increase
      supply, respond to current demand, and enhance the working environment to benefit
      recruitment and retention. Four areas are highlighted as exemplars of effort:
      supply and demand; work environment; new partnerships and public/private
      ventures; and patient-centered and essential patient-safe care.

PMID- 15485303
TI  - Health literacy: a key ingredient for managing personal health.

PMID- 15485304
TI  - The digital divide: how wide and how deep?

PMID- 15485305
TI  - Nurse reinvestment act: implications for the nursing profession: discussion with
      Denise Geolot.

PMID- 15485306
TI  - The ODAC chronicles: part 1. My first ODAC experience.

PMID- 15485308
TI  - Aprepitant: a neurokinin-1 receptor antagonist for the treatment of chemotherapy
      induced nausea and vomiting.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant
      deterioration in quality of life, and although the use of 5-hydroxytryptamine-3
      (5-HT3) receptor antagonists plus dexamethasone has significantly improved the
      control of acute CINV, delayed nausea and vomiting remain a significant clinical
      problem. Aprepitant (Emend), Merck) is the first agent available in the new drug
      class of neurokinin-1 receptor antagonists. When added to a standard regimen of a
      5-HT3 receptor antagonist and dexamethasone in patients receiving highly
      emetogenic chemotherapy, it improves the complete response rate of acute CINV.
      Aprepitant also improves the complete response of delayed CINV when used in
      combination with dexamethasone compared with dexamethasone alone. Based on these
      studies, new guidelines for the prevention of CINV have been developed for
      patients receiving highly emetogenic chemotherapy. The use of aprepitant in
      patients receiving moderately emetogenic chemotherapy will await the review and
      analysis of recently completed Phase III trials. Aprepitant is a substrate, a
      moderate inhibitor and an inducer of cytochrome P450 (CYP)3A4 and CYP2C9. Drug
      interactions should be monitored when aprepitant is coadministered with agents
      affected by CYP3A4 and CYP2C9 isoenzymes. The safety and efficacy of aprepitant
      has not been established in pediatric or adolescent patients, and aprepitant has
      not been evaluated in the treatment of patients with established nausea and
      vomiting. Future studies may consider the use of aprepitant with current and
      other new agents in moderately and highly emetogenic chemotherapy, as well in the
      clinical settings of multiple-day chemotherapy and bone marrow transplantation.

PMID- 15485309
TI  - Celecoxib: a novel treatment for lung cancer.
AB  - Lung cancer is by far the leading cause of cancer-related deaths. Overall
      survival is poor and has not improved substantially over the last 50 years.
      Therefore, it is clear that novel and more effective treatments are needed to
      improve the outcome of therapy. Recent attention has been drawn to the role of
      cyclooxygenase (COX)-2 in the pathogenesis of cancer, and it has been considered
      as an attractive target for therapeutic and chemopreventive strategies in lung
      cancer patients. Celecoxib (Celebrex), Pfizer), a selective COX-2 inhibitor and
      potent anti-inflammatory agent, has been approved for the treatment of
      osteoarthritis and rheumatoid arthritis. This orally administered agent is
      generally well tolerated and has almost no gastrointestinal or renal toxicity.
      Phase II clinical trials suggest that COX-2 inhibition by celecoxib would enhance
      response to cytotoxic chemotherapy or radiation therapy through interference with
      cellular proliferation and tumor angiogenic processes, promotion of apoptosis and
      immune surveillance, or other possible mechanisms. Celecoxib has shown promising
      antitumor efficacy in lung cancer and a large variety of solid tumors that rely
      on COX-2-related mechanisms for growth and survival. This article reviews the
      profile of celecoxib and evidence supporting its role in the therapy of lung
      cancer.

PMID- 15485310
TI  - Darbepoetin alfa for the treatment of cancer-related anemia: an update.
AB  - Anemia is a common and potentially debilitating complication of cancer.
      Darbepoetin alfa (Aranesp, Amgen) has been in routine clinical use for the
      treatment of chemotherapy-induced anemia since 2002. The extended half-life of
      darbepoetin alfa permits less frequent and consequently more flexible dosing than
      other erythropoietic therapies. Data suggest that hemoglobin levels can be
      effectively and safely increased with darbepoetin alfa in cancer patients who are
      receiving chemotherapy (patients with treatment-induced anemia), and in those who
      are not receiving chemotherapy (patients with tumor-induced anemia). This review
      provides an overview of clinical trial results, particularly those exploring
      flexible, extended dosing schedules.

PMID- 15485311
TI  - Cladribine: from the bench to the bedside--focus on hairy cell leukemia.
AB  - Cladribine is an adenosine deaminase-resistant deoxyadenosine analog with a
      unique mechanism of action. It is directly toxic towards both resting and
      proliferating human lymphocytes and monocytes. The development of this compound
      into clinical practice best exemplifies rational drug development and the success
      of translational research. Cladribine is well established as first-line treatment
      for hairy cell leukemia, inducing an overall response rate of 75-100%, with the
      majority being complete responses following only a single 7-day treatment course.
      The 9-year overall survival for hairy cell leukemia is currently 97%. Cladribine
      has also proven useful in the treatment of a variety of other hematologic
      malignancies, and its current place in the oncologic therapeutic armamentarium,
      as well as in potential areas of development, are outlined.

PMID- 15485312
TI  - Therapy for recurrent malignant glioma in adults.
AB  - Malignant gliomas are the most common form of primary brain tumors in adults.
      Although the prognosis remains poor, there has been recent progress in the
      treatment of these tumors. Standard therapy for patients with this disease will
      be reviewed, together with more novel approaches such as targeted molecular
      therapies, angiogenesis inhibitors, immunotherapies, gene therapies and
      intratumoral therapies.

PMID- 15485313
TI  - Treatment of brain metastases in uncommon tumors.
AB  - Melanoma spreads to the CNS with an incidence of 4 to 20%. Metastases from cancer
      of the colorectal and genitourinary tract, as well as sarcoma, are less frequent
      (1%). Surgery should be considered for single brain metastases in patients with
      controllable disease. Stereotactic needle biopsy may still be worthwhile to
      confirm diagnosis, and also in patients whose tumors are considered unresectable.
      Whole-brain radiotherapy is the treatment of choice for most brain metastases,
      since more than 70% of patients have multiple metastases at the time of
      diagnosis. Radiosurgery is particularly useful for patients unable to tolerate
      surgery and for patients with lesions inaccessible to surgery. Chemotherapy could
      be useful in patients with asymptomatic brain metastases and uncontrolled
      extracranial disease, depending on performance status and previous chemotherapy
      received.

PMID- 15485314
TI  - Clinical management of medulloblastoma in adults.
AB  - Although medulloblastoma is the most common malignant brain tumor in children,
      30% of cases occur in adults. Recent therapeutic advances in the treatment of
      average-risk childhood medulloblastoma have emphasized the reduction of treatment
      related toxicity while improving progression-free survival. However, lessons
      learned from the pediatric experience have not been widely applied to the adult
      population in Phase II or randomized clinical trials. This review will compare
      adult and pediatric medulloblastoma, highlight case series of adults treated at
      major academic institutions, and suggest directions for the contemporary
      management of adults with medulloblastoma.

PMID- 15485315
TI  - Molecular neuro-oncology and the development of targeted therapeutic strategies
      for brain tumors. Part 3: brain tumor invasiveness.
AB  - Brain tumors are a diverse group of malignancies that remain refractory to
      conventional treatment approaches. Molecular neuro-oncology has now begun to
      clarify the transformed phenotype of brain tumors and identify oncogenic pathways
      that might be amenable to targeted therapy. Cellular invasion of surrounding
      brain is one of the key features of brain tumor behavior and is currently under
      evaluation for potential therapeutic targets. Tumor invasion occurs in the
      context of the extracellular matrix (ECM) of the brain and involves the
      interaction between cell-surface adhesion molecules, such as integrins and
      proteins embedded within the ECM. The overexpression of integrins is often
      associated with invasive behavior and can be inhibited by targeted approaches
      such as antibodies, antisense constructs and cyclic peptides. Tumor cell-secreted
      matrix metalloproteinases and serine proteinases degrade ECM proteins and provide
      space for movement and infiltration. The expression of proteinases positively
      correlates with tumor grade and infiltrative capacity. Proteinase activity can be
      reduced by several methods, including antibodies and small-molecule inhibitors
      such as marimastat. Early clinical trials suggest that marimastat may have
      activity in combination with traditional chemotherapy regimens. Further
      development of targeted therapies designed to inhibit tumor infiltration, and
      evaluation of these new agents in clinical trials, will be needed to improve
      survival and quality of life for patients with brain tumors.

PMID- 15485316
TI  - Adjuvant therapy for malignant melanoma.
AB  - Malignant melanoma is increasing in incidence worldwide, and many patients remain
      at a significant risk of recurrence following surgical resection. Over the past
      30 years, interferon-alpha has been the only agent approved for adjuvant therapy
      of melanoma. This review summarizes the rationale for adjuvant therapy, and
      discusses the roles of interferon, immunotherapy, chemotherapy and radiation
      therapy in the adjuvant setting. New approaches and novel combinations that
      appear promising for the adjuvant therapy of malignant melanoma are also
      outlined.

PMID- 15485317
TI  - Laparoscopic surgery for melanoma metastases to the adrenal gland.
AB  - The probability of developing cutaneous melanoma is now predicted to be one in 55
      for males and one in 88 for females. Although melanoma is relatively uncommon
      compared with other malignancies such as breast (one in seven) or prostate cancer
      (one in six), the incidence is growing at an alarming rate. The development of
      novel strategies for the management of advanced disease will become even more
      urgent and require continued and controlled investigations over the next 10
      years. Surgery is effective for the palliation of isolated resectable metastases.
      However, most patients with Stage IV melanoma have widespread disease and are not
      cured by metastasectomy. For the few individuals with isolated adrenal metastases
      from melanoma, complete resection appears to confer a survival advantage. New
      data are emerging about the efficacy and outcome of laparoscopic adrenalectomy
      for malignant lesions. However, the natural history of laparoscopic surgery for
      these lesions is still unknown. The indications for and limitations of
      laparoscopic adrenalectomy for metastatic melanoma are discussed.

PMID- 15485318
TI  - Role of farnesyltransferase inhibitors in hematologic malignancies.
AB  - The treatment of hematologic malignancies has progressed in the last few years.
      Identification of new pathways and target molecules in leukemia has ushered in a
      promising new era of therapy. Ras mutations have recently been implicated in the
      pathogenesis of acute leukemia, and inhibition of Ras signaling through the use
      of farnesyltransferase inhibitors (FTIs) has shown promise in early trials in
      acute myeloid leukemia (AML). Responses have not correlated with the presence of
      Ras mutations, suggesting that novel pathways are involved. In several early
      trials, FTIs have shown activity as single agents in poor-risk AML, suggesting a
      potential role in combination with standard chemotherapy. FTIs are now being
      tested in other clinical settings, such as myelodysplasia, chronic myelogenous
      leukemia and multiple myeloma, with encouraging preliminary activity.

PMID- 15485319
TI  - Optical imaging of mice in oncologic research.
AB  - Optical imaging is a highly sensitive technique for detecting a variety of
      cellular, molecular and tissue processes in vivo and in vitro. Optical imaging
      systems are well suited to in vivo imaging in the laboratory setting for a
      variety of reasons, including low cost, ease of use and efficiency of imaging.
      Commercial availability of optical imaging detector systems has allowed more
      investigators to explore their use for a variety of applications. The ever
      increasing number of naturally occurring and modified near-infrared probes,
      photoproteins, and fluorescent probes provide opportunities to improve detection
      and labeling. Technical advances in detector systems and imaging software have
      allowed the refinement of established techniques. Furthermore, the availability
      of mice genetically altered to express photo and fluorescent proteins have
      spurred tremendous growth in this area of research.

PMID- 15485320
TI  - Nonmyeloablative transplantation for solid tumors: a new frontier for allogeneic
      immunotherapy.
AB  - The failure of conventional chemotherapy to improve survival in a large
      percentage of patients with advanced solid tumors has prompted the development of
      alternative anticancer approaches. Conventional allogeneic hematopoietic stem
      cell transplantation (HSCT) relies on myeloablative conditioning to eradicate the
      underlying disease, as well as suppress the patient's immune response, allowing
      engraftment of the donor's lymphohematopoietic system. Such preparative regimens
      are frequently associated with serious hematologic and nonhematologic toxicities,
      resulting in substantial morbidity and mortality. A significant curative
      component of allogeneic HSCT is the immune-mediated graft-versus-tumor (GVT)
      effect. Nonmyeloablative preparative regimens were designed to suppress host
      immunity to allow for sufficient engraftment of the donor immune system for the
      subsequent generation of GVT effects. These relatively low-dose preparative
      regimens are generally well tolerated and are associated with a reduction in the
      risk of transplant-related mortality. Nonmyeloablative HSCT provides a safer
      platform to explore the efficacy of allogeneic HSCT in patients with solid
      tumors. Initial reports have demonstrated that GVT may occur against several
      different solid tumors, including renal cell carcinoma, ovarian cancer, breast
      cancer and others. Based on these preliminary encouraging results, further
      exploration of nonmyeloablative HSCT for solid tumors is clearly warranted. The
      development of strategies to decrease graft-versus-host disease while enhancing
      post-transplant antitumor immunity will hopefully be forthcoming in the near
      future.

PMID- 15485321
TI  - Endocrine therapy for early breast cancer.
AB  - Breast cancer is a significant cause of morbidity and mortality. Adjuvant
      tamoxifen therapy for estrogen receptor-positive early breast cancer has had a
      major impact on mortality in clinical trials, and the observation that breast
      cancer mortality started to decline shortly after widespread tamoxifen
      prescription was introduced in several countries inevitably leads us to conclude
      that this intervention is responsible. Aromatase inhibitor therapy will
      undoubtedly become part of everyday practice in the future, although the
      optimization of aromatase inhibitor therapy as part of the overall endocrine
      package needs further definition. However, to suppose that a unified optimal
      sequence and duration is applicable to all patients is probably a fallacy, and
      underlying the overall effects of different treatments are individual patients
      with individual but potentially classifiable tumors requiring different
      management strategies. Characterization and individualization of therapies based
      on gene and proteomic expression profiling is a massive research undertaking, but
      could guide us towards a fairly simple set of key gene or protein expression
      profiles to guide adjuvant hormonal, chemotherapeutic or new biologic agent
      strategies that will define optimal treatment packages for women with early
      breast cancer. Within the next 5 years, the clinical reservations regarding
      adjuvant aromatase inhibitors and financial obstacles to access the aromatase
      inhibitors are likely to be overcome and, unless we are able to identify a cohort
      of women who will gain no additional benefit or who have a better outcome with
      tamoxifen, most postmenopausal women will be treated with aromatase inhibitor
      monotherapy or a sequential combination utilizing an aromatase inhibitor.

PMID- 15485322
TI  - Impact and treatment of cancer during pregnancy.
AB  - Cancer is the second most common cause of death in the reproductive years and
      complicates up to one in 1000 pregnancies. When cancer is diagnosed during
      pregnancy, the management strategy must take into account both the mother and
      developing fetus. In this article, the four most common malignancies diagnosed in
      pregnant patients--cervical and breast cancer, malignant melanoma and lymphoma-
      will be reviewed, with an emphasis on the impact of the diagnosis and management
      on the pregnant patient and the developing fetus.

PMID- 15485323
TI  - Sentinel lymph node biopsy for breast cancer: from investigational procedure to
      standard practice.
AB  - Sentinel lymph node biopsy, popularized in melanoma, has revolutionized the
      management of breast cancer. While the morbidity associated with axillary node
      dissection was once thought to be a requisite risk in order to appropriately
      stage the axilla, large validation studies have demonstrated that sentinel lymph
      node biopsy is a minimally invasive technique that can accurately predict nodal
      status. This technique has become an accepted practice in many centers, but there
      remain many controversies surrounding the technique itself, the pathologic
      evaluation of the sentinel node and the optimal management of patients with
      minimal nodal disease. The historic roots of this technique are discussed, along
      with the controversial issues surrounding the technique and the clinical trials
      that are currently ongoing.

PMID- 15485324
TI  - Treatment of laryngeal cancer: the permanent challenge.
AB  - There are many options to treat larynx cancers. Throughout the 20th century,
      surgical research has provided many partial surgery techniques (either open
      surgery or endoscopic CO2 surgery). In parallel, the modification of radiotherapy
      schedules has notably improved the local control with definitive irradiation. The
      appearance of active chemotherapy regimens has also modified the concept of
      treatment for advanced disease, allowing a decrease in the total indications of
      laryngectomy, although this remains the treatment of choice in some cases. The
      selection of the most appropriate treatment is based on a multidisciplinary
      approach. Early diseases may be treated by open surgery, endoscopic laser CO2
      surgery or irradiation. Some advanced diseases may be treated by partial surgery,
      but the majority are theoretically candidates for radical surgery when
      resectable. In many instances, but not in all, chemotherapy-based larynx
      preserving protocols may avoid performing such mutilating surgery. When
      inoperable, larynx cancers are better treated by combined chemotherapy and
      irradiation when the performance status of the patient is compatible with such an
      intensive regimen.

PMID- 15485325
TI  - Serum tumor markers in patients with breast cancer.
AB  - Several serum tumor markers have been investigated in patients with breast cancer
      for assessing outcome, predicting recurrence and monitoring the therapeutic
      response. There is a general consensus concerning their limited application in
      diagnosing malignancy; however, serum tumor markers can be considered for the
      early detection of recurrence. The most effective markers for this indication are
      cancer antigens (CA)15-3 and 27.29, and c-erbB-2, although their efficacy in
      establishing disease progression has not been determined to date. In terms of
      evaluating prognosis and predicting response to therapy, only the expression of c
      erbB-2 has clinical evidence. To conclude, at present, no serum tumor marker is
      cost effective, and none can be used with confidence in the decision making
      regarding breast cancer patients.

PMID- 15485326
TI  - Bioterrorism: what level is the threat and are vaccines the answer?

PMID- 15485327
TI  - Vaccines to remember: managing health in our twilight years.

PMID- 15485328
TI  - More women and adolescents needed in HIV vaccine trials.

PMID- 15485330
TI  - Dengue, one of the great emerging health challenges of the 21st century.

PMID- 15485331
TI  - M-Vax: an autologous, hapten-modified vaccine for human cancer.
AB  - The author has devised a novel approach to the immunotherapy of cancer based on
      modification of autologous tumor cells with the hapten, dinitrophenyl (DNP). This
      technology is being developed by AVAX Technologies (MO, USA) as a treatment for
      melanoma under the brand name, M-Vax. The treatment program consists of multiple
      intradermal injections of DNP-modified autologous tumor cells mixed with bacille
      Calmette-Guerin as an immunological adjuvant. Administration of DNP vaccine to
      patients with metastatic melanoma induces a unique reaction--the development of
      inflammation in metastatic masses. Following DNP-vaccine treatment, almost all
      patients develop delayed-type hypersensitivity (DTH) to autologous, DNP-modified
      melanoma cells and about half also exhibit DTH to autologous, unmodified tumor
      cells. The toxicity of the vaccine is mild, consisting mainly of papules or
      pustules at the injection sites. Clinical trials have been conducted in two
      populations of melanoma patients: Stage IV with measurable metastases, and
      clinical Stage III patients rendered tumor-free by lymphadenectomy. There were 11
      antitumor responses in 83 patients with measurable metastases: two complete, four
      partial and five mixed. In 214 Stage III patients the 5-year overall survival
      rate was 44%, which compares favorably with the reported surgical rate of 20-25%.
      In both populations, the induction of DTH to unmodified autologous tumor cells
      was associated with significantly longer survival. This is a platform technology
      that is adaptable to other human cancers and early trials indicate immunological
      activity in ovarian and renal cell carcinomas.

PMID- 15485332
TI  - Garden-variety vaccines: antigens derived from transgenic plants.
AB  - The discovery of new vaccines can result from deletion of virulence determinants
      from a specific pathogen or from identification of target antigens that stimulate
      a protective immune response. Vaccine development will become less empirical as
      applications of genomics, proteomics and reverse vaccinology are exploited, and
      new protective antigens will emerge for inclusion in the vaccines of the future.
      However, production and purification of these new antigens for oral and
      parenteral use using traditional expression systems, will be expensive and
      unattractive to vaccine manufacturers who see the vaccine market as economically
      uninviting. Cost is one of the persistent barriers to deployment of new vaccines
      to populations that need them most urgently. This factor will inhibit the
      development and distribution of safe and effective new vaccines against high
      priority pathogens.

PMID- 15485333
TI  - Control and lot release of meningococcal group C conjugate vaccines.
AB  - Meningococcal group C conjugate vaccines were first introduced to the UK in 1999.
      To date, the vaccines have been demonstrated to have an efficacy of approximately
      90% and have since been adopted by other countries worldwide. The development of
      control tests used for lot release of meningococcal group C vaccines has been
      based on those used for Haemophilus influenzae type b conjugates, the key
      criteria being measurement of free saccharide and conjugate integrity by
      physicochemical means. In future, meningococcal group C vaccines are likely to be
      replaced by multivalent formulations containing different components in
      combination. This will present a new challenge for regulatory authorities and
      more extensive testing will be required to ensure vaccine safety and efficacy.

PMID- 15485334
TI  - Rickettsial vaccines: the old and the new.
AB  - In the past century vaccine development for prevention of rickettsial diseases
      has been prolific. However, in the past 20 years no new rickettsial vaccine has
      been manufactured and there are currently no new or old rickettsial vaccines
      licensed. Early rickettsial vaccines were difficult, expensive and very hazardous
      to produce. Molecular biology techniques of today are currently being used to
      develop new rickettsial vaccines that are standardized, inexpensive, nonhazardous
      and efficacious.

PMID- 15485335
TI  - Global perspectives on vaccine financing.
AB  - Despite the great promise of immunization and recent progress in immunizing
      children throughout the developing world, a global crisis in vaccine R&D, supply
      and delivery is faced. This article reviews how the global US6 billion dollars
      vaccine market is structured and its attractiveness to vaccine suppliers, the
      international two-tiered pricing system in which high-income countries generate
      about 82% of vaccine revenues but represent only 12% of the doses, the impact of
      schedule divergence as high-income and developing countries introduce different
      vaccines, the role of the US government, and possible approaches to ameliorate
      the crisis.

PMID- 15485336
TI  - T-cell epitope peptide vaccines.
AB  - T-cell immunotherapy is a promising treatment option for cancer. The
      identification of tumor antigens that are recognized by the immune system has
      allowed for the generation of vaccines for various malignancies. Due to the ease
      of manufacturing and characterizating peptide-based vaccines they have been used
      to stimulate antitumor T-cells. This article will review the use of peptide-based
      vaccines for the treatment of cancer by inducing antitumor T-lymphocyte
      responses.

PMID- 15485337
TI  - Vaccines against Coxiella infection.
AB  - Coxiella burnetii is an obligate intracellular bacterium that causes a worldwide
      zoonotic disease, Q fever. Since C. burnetii infection is an occupational hazard
      and could develop into severe chronic disease in humans, vaccination should be
      considered to protect individuals at-risk of contact with naturally infected
      animals or exposure to the agents. Although several vaccines produced from Phase
      I whole-cell C. burnetii are effective in protecting against the infection in
      humans, vaccination of previously sensitized people can induce severe local and
      occasional systemic reactions. Safe use of these vaccines requires screening of
      potential vaccinees by skin tests, serological tests, or in vitro lymphocyte
      proliferation assay. Since these procedures are time-consuming and costly, they
      limit the use of whole-cell vaccines in a mass vaccination program. Efforts have
      been underway to develop a safer, more effective new-generation vaccine that will
      not cause adverse reactions when given to someone with pre-existing immunity.
      This article describes new information relating to the characterization of
      acquired immunity to C. burnetii infection that will provide a fundamental
      understanding of the development of protective immunity against Q fever. Recent
      works focused on development of recombinant vaccines against this pathogen offers
      promise in the pursuit of a new Q fever vaccine.

PMID- 15485338
TI  - Enterotoxigenic Escherichia coli virulence factors and vaccine approaches.
AB  - Enterotoxigenic Escherichia coli (ETEC) is recognized as one of the major causes
      of infectious diarrhea in developing countries. Worldwide, the incidence of ETEC
      infections is estimated to result in 650 million cases of diarrhea and 380,000
      deaths in children under 5 years of age. ETEC is also an important cause of
      travelers' diarrhea in people traveling to endemic regions of the world. Although
      ETEC is an uncommon cause of infections in the USA, there have been 14 reported
      outbreaks of ETEC in the USA and seven on cruise ships over the 20-year period
      between 1975 and 1995. ETEC strains are comprised of a large number of serotypes
      that produce a variety of colonization factors and enterotoxins. On infection,
      ETEC first establishes itself by adhering to the epithelium of the small
      intestine via one or more colonization factor antigens or coli surface proteins.
      Once established, ETEC expresses one or more enterotoxin(s), which results in the
      production of secretory diarrhea. While the need for an efficacious, easily
      administered vaccine is great, there are currently no licensed ETEC vaccines
      available for use in endemic countries or for US travelers.

PMID- 15485339
TI  - Pneumococcal vaccine development.
AB  - A 7-valent pneumococcal conjugate vaccine has demonstrated an impact on
      pneumococcal bacteremia in the immunized pediatric population, extending to
      nonimmunized adults via herd immunity. A considerable reduction of all-cause
      pediatric pneumonia has also been found. The impact on all-cause pediatric otitis
      is limited, but postlicensure data suggests stronger reductions. Higher valency
      conjugate vaccines are now under development (11V or more). Licensed 23-valent
      pneumococcal polysaccharide vaccines have been available since 1983 with a
      demonstrated impact on adult pneumococcal bacteremia. The burden of adult
      nonbacteremic pneumococcal pneumonia has remained high and efforts to develop
      improved adult pneumococcal vaccines have been initiated that include conjugates
      and pneumococcal proteins.

PMID- 15485340
TI  - Antigen-tailored therapy based on the inflammatory theory of atherosclerosis.
AB  - In recent years, considerable data has been provided to support the role of the
      immune system in atherosclerosis. These reports came from studies involving
      knockout murine models of atherosclerosis and human subjects. The notion that
      inflammatory mechanisms are operable in atherogenesis has fueled a series of
      studies demonstrating that autoimmune responses are also evident in the
      atherosclerotic lesions and appear to influence the initiation and progression of
      the plaque. The principal autoantigens that have been suggested as potential
      triggers of autoimmune responses in atherosclerosis are modified forms of low
      density lipoproteins, heat shock proteins and beta2 glycoprotein I. Immunization
      against these antigens influenced the generation of lesions and adoptive transfer
      studies of lymphocytes reactive to some of these antigens have also been
      demonstrated to enhance the growth of the plaques. The realization that
      autoimmune-like responses may play a role in the progression of atherosclerotic
      lesions has paved the way for exciting modes of manipulating lesions,
      irrespective of the effect on the lipid profile. Thus, recent studies indicate
      that oral tolerance with antigens or derivatives could suppress the respective
      immune responses and reduce the extent of the lesions in transgenic
      atherosclerosis-prone mice. These observations should be further explored and if
      validated, could represent novel modalities for influencing atherogenessis in
      humans.

PMID- 15485341
TI  - Genetic testing in primary care.
AB  - Rapid advances in genetic research are leading to an expanding array of genetic
      tests. Primary care providers will increasingly be challenged to identify
      patients whose symptoms, physical findings, or family history indicate the need
      for genetic testing, and to determine how to use genetic information most
      effectively to improve disease prevention. In addressing these challenges,
      practitioners will need to consider the range of different uses of genetic
      testing, including diagnosis in symptomatic and asymptomatic people, risk
      assessment, reproductive decision-making, and population screening. They will
      need a set of core skills and knowledge to evaluate family history and to
      recognize clinical findings that indicate genetic risk. At the same time, the
      primary care perspective will contribute to the evaluation of appropriate uses of
      genetic testing. A partnership between medical genetics and primary care will
      help to ensure the development of effective policies, educational tools, and
      practice guidelines for the coming era of genomic health care.

PMID- 15485342
TI  - Comparative genomics.
AB  - The genomes from three mammals (human, mouse, and rat), two worms, and several
      yeasts have been sequenced, and more genomes will be completed in the near future
      for comparison with those of the major model organisms. Scientists have used
      various methods to align and compare the sequenced genomes to address critical
      issues in genome function and evolution. This review covers some of the major new
      insights about gene content, gene regulation, and the fraction of mammalian
      genomes that are under purifying selection and presumed functional. We review the
      evolutionary processes that shape genomes, with particular attention to variation
      in rates within genomes and along different lineages. Internet resources for
      accessing and analyzing the treasure trove of sequence alignments and annotations
      are reviewed, and we discuss critical problems to address in new bioinformatic
      developments in comparative genomics.

PMID- 15485343
TI  - Genetic screening: carriers and affected individuals.
AB  - Genetic screening utilizes analytical approaches adapted for high throughput to
      identify carrier and affected individuals in a targeted population. Currently,
      genetic screening focuses on carrier screening, prenatal screening, and newborn
      screening. Newborn screening should serve as a model for all genetic screening,
      with more than forty years of experience and numerous lessons learned. As with
      all genetic screening, there are policy concerns in newborn screening regarding
      which disorders and technologies should be selected, and how centralized or
      decentralized the process to set policy should be. The need to share experiences
      and develop databases transcends all other policy considerations in genetic
      screening. The future will see population-based screening for adult-onset
      disorders. However, there needs to be extensive research to define predictive
      risk for various ethnocultural groups and to determine effective interventions.
      Ethical concerns regarding the timing of population screening, as well as the
      scope of use of information, will need to be resolved if genomic medicine will
      achieve its promise of a predictive, preventive, and personalized medicine.

PMID- 15485344
TI  - Nutritional genomics.
AB  - Nutritional genomics has tremendous potential to change the future of dietary
      guidelines and personal recommendations. Nutrigenetics will provide the basis for
      personalized dietary recommendations based on the individual's genetic make up.
      This approach has been used for decades for certain monogenic diseases; however,
      the challenge is to implement a similar concept for common multifactorial
      disorders and to develop tools to detect genetic predisposition and to prevent
      common disorders decades before their manifestation. The preliminary results
      involving gene-diet interactions for cardiovascular diseases and cancer are
      promising, but mostly inconclusive. Success in this area will require the
      integration of different disciplines and investigators working on large
      population studies designed to adequately investigate gene-environment
      interactions. Despite the current difficulties, preliminary evidence strongly
      suggests that the concept should work and that we will be able to harness the
      information contained in our genomes to achieve successful aging using behavioral
      changes; nutrition will be the cornerstone of this endeavor.

PMID- 15485345
TI  - Africans and Asians abroad: genetic diversity in Europe.
AB  - Besides its obvious intrinsic value, knowledge of population history, and of the
      demographic and evolutionary changes that accompany it, has proven fundamental to
      address applied research in human genetics. In this review we place current
      European genetic diversity in the context of the global human genome diversity
      and review the evidence supporting a recent African origin of the Europeans. We
      then discuss the results and the interpretation of genetic studies attempting to
      quantify the relative importance of various gene flow processes, both within
      Europe and from Asia into Europe, focusing especially on the initial, Paleolithic
      colonization of the continent, and on later, Paleolithic postglacial and
      Neolithic dispersals. Finally, we discuss how knowledge of the patterns of
      genetic diversity in Europe, and of their inferred generating processes, can be
      extremely useful in planning health care and in biomedical research.

PMID- 15485346
TI  - Finding prostate cancer susceptibility genes.
AB  - Prostate cancer is a heterogeneous disease with multiple loci contributing to
      susceptibility. Traditionally, genome-wide scans using high-risk families have
      utilized stratification by number of affected individuals, family history of
      other cancers, or family age at diagnosis to improve genetic homogeneity. In
      addition to locus heterogeneity, for later onset diseases such as prostate
      cancer, a major limitation to mapping efforts is that key parental DNA samples
      are rarely available. The lack of available samples from upper generations
      reduces inheritance information, and as a result, the standard 10-cM genome scan
      does not provide full power to detect linkage. To increase the ability to find
      disease-associated loci, much denser genome-wide scans must be undertaken in
      multiple ethnic groups. In addition, new ways of defining homogenous subsets of
      families need to be developed.

PMID- 15485347
TI  - Molecular networks in model systems.
AB  - Model organisms, especially the budding yeast, are leading systems in the
      transformation of biology into an information science. With the availability of
      genome sequences and genome-scale data generation technologies, the extraction of
      biological insight from complex integrated molecular networks has become a major
      area of research. Here I examine key concepts and review research developments. I
      propose specific areas of research effort to drive network analysis in directions
      that will promote modeling with increasing predictive power.

PMID- 15485348
TI  - Genetics of atherosclerosis.
AB  - Atherosclerosis, the primary cause of coronary artery disease (CAD) and stroke,
      is a disorder with multiple genetic and environmental contributions. Genetic
      epidemiologic studies have identified a surprisingly long list of genetic and
      nongenetic risk factors for CAD. However, such studies indicate that family
      history is the most significant independent risk factor (15, 52, 77). Many
      Mendelian disorders associated with atherosclerosis, such as familial
      hypercholesterolemia (FH), have been characterized, but they explain only a small
      percentage of disease susceptibility (although a substantial fraction of early
      CAD). Most cases of myocardial infarction (MI) and stroke result from the
      interactions of multiple genetic and environmental factors, none of which can
      cause disease by itself. Successful discovery of these genetic factors will
      require using complementary approaches with animal models, large-scale human
      genetic studies, and functional experiments. This review emphasizes the common,
      complex forms of CAD.

PMID- 15485349
TI  - Medical genetics in developing countries.
AB  - Since Watson & Crick's 1953 description of the structure of DNA, significant
      progress has been achieved in the control of congenital disorders, most of which
      has benefited industrialized countries. Little advantage accrued to developing
      nations, most of which in the same time frame achieved a significant
      epidemiological transition, resulting in congenital disorders attaining public
      health significance. The burden of congenital disorders in these lower-resource
      countries is high and they need to develop medical genetic services. We present a
      new pragmatic approach for the care and prevention of congenital disorders in
      these countries, pioneered initially by the World Health Organization.

PMID- 15485350
TI  - Proteomics.
AB  - The genome sequences of important model systems are available and the focus is
      now shifting to large-scale experiments enabled by this data. Following in the
      footsteps of genomics, we have functional genomics, proteomics, and even
      metabolomics, roughly paralleling the biological hierarchy of the transcription,
      translation, and production of small molecules. Proteomics is initially concerned
      with determining the structure, expression, localization, biochemical activity,
      interactions, and cellular roles of as many proteins as possible. There has been
      great progress owing to novel instrumentation, experimental strategies, and
      bioinformatics methods. The area of protein-protein interactions has been
      especially fruitful. First pass interaction maps of some model organisms exist,
      and the proteins in many important organelles are about to be determined.
      Researchers are also beginning to integrate large-scale data sets from various
      "omics" disciplines in targeted investigations of specific biomedical areas and
      in pursuit of a general framework for systems biology.

PMID- 15485351
TI  - Population genetics, history, and health patterns in native americans.
AB  - Over the past two decades, detailed studies of mitochondrial DNA and the Y
      chromosome have increased our understanding of the history and population
      genetics of Native American populations. Variation in autosomal DNA has also been
      investigated, but to a more limited extent. A low level of genetic diversity in
      Native American populations is a robust finding from all lines of evidence. In
      contrast to the previous multiple migration scenarios for the Pleistocene
      peopling of the Americas, it now seems that a single migration satisfactorily
      explains the genetic data. Native Americans show greater genetic similarity to
      populations in east central Asia than they do to the current easternmost Siberian
      populations. Recent studies on the Y chromosome indicate a date of entry (about
      17,000 years ago) into the Americas roughly consistent with the archaeological
      record. Native Americans experienced two episodes of reduced population size: one
      with the peopling of the Americas and the other with European contact. The former
      is the more important determinant for the number of gene lineages and founding
      haplotypes seen in populations. It may also be an important determinant of the
      genetic variation underlying common complex diseases, and especially diabetes.
      The tribal structure of contemporary Native American populations is relevant to
      the distribution of rare Mendelian disorders because most tribes constitute
      relatively small, semi-independent gene pools. This leads us to expect that the
      allelic spectrum for Mendelian diseases will be simple within individual tribes
      but complex for Native Americans as a whole.

PMID- 15485352
TI  - Variation in human meiotic recombination.
AB  - As recently as 20 years ago, there was relatively little information about the
      number and distribution of recombinational events in human meiosis, and we knew
      virtually nothing about factors affecting patterns of recombination. However, the
      generation of a variety of linkage-based genetic mapping tools and, more
      recently, cytological approaches that enable us to directly visualize the
      recombinational process in meiocytes, have led to an increased understanding of
      human meiosis. In this review, we discuss the different approaches used to study
      meiotic recombination in humans, our understanding of factors that affect the
      number and location of recombinational events, and clinical consequences of
      variation in the recombinational process.

PMID- 15485353
TI  - Comparative primate genomics.
AB  - With the completion of the human genome sequence and the advent of technologies
      to study functional aspects of genomes, molecular comparisons between humans and
      other primates have gained momentum. The comparison of the human genome to the
      genomes of species closely related to humans allows the identification of genomic
      features that set primates apart from other mammals and of features that set
      certain primates notably humans apart from other primates. In this article, we
      review recent progress in these areas with an emphasis on how comparative
      approaches may be used to identify functionally relevant features unique to the
      human genome.

PMID- 15485354
TI  - Autism as a paradigmatic complex genetic disorder.
AB  - Autism is one of the most heritable complex disorders, with compelling evidence
      for genetic factors and little or no support for environmental influence. The
      estimated prevalence of autism has increased since molecular genetic studies
      began, owing to loosening of diagnostic criteria and, more importantly, to more
      complete ascertainment strategies. This has led to a reduction in the sibling
      relative risk, but strong heritability estimates remain. It is essential to
      recognize that genetics is the only current approach to understanding the
      pathophysiology of autism in which there is not the usual concern about whether
      one is studying a consequence rather than a cause. There are hundreds, if not
      thousands, of patients with autism spectrum disorder with documented single-gene
      mutations or chromosomal abnormalities. Autism may be one of the most complex,
      yet strongly genetic, disorders in which chromosomal disorders, relatively rare
      highly penetrant mutations, and multiplicative effects of common variants all
      have support in different cases and families. The field of complex genetics is
      replete with many researchers and reviewers who want to promote their overly
      focused interest in one method at the exclusion of others. However, it is
      essential that the restricted interests of patients with autism not be reflected
      in overly restrictive genetic approaches if we are to better understand the
      genetics of autism in the most expeditious and thorough manner.

PMID- 15485356
TI  - Plant genomics: the third wave.
AB  - Completing the primary genomic sequence of Arabidopsis thaliana was a major
      milestone, being the first plant genome and only the third high-quality finished
      eukaryotic genome sequence. Understanding how the genome sequence comprehensively
      encodes developmental programs and environmental responses is the next major
      challenge for all plant genome projects. This requires fully characterizing the
      genes, the regulatory sequences, and their functions. We discuss several
      functional genomics approaches to decode the linear sequence of the reference
      plant Arabidopsis thaliana, including full-length cDNA collections, microarrays,
      natural variation, knockout collections, and comparative sequence analysis.
      Genomics provides the essential tools to speed the work of the traditional
      molecular geneticist and is now a scientific discipline in its own right.

PMID- 15485357
TI  - Epigenetics and human disease.
AB  - Epigenetics is comprised of the stable and heritable (or potentially heritable)
      changes in gene expression that do not entail a change in DNA sequence. The role
      of epigenetics in the etiology of human disease is increasingly recognized with
      the most obvious evidence found for genes subject to genomic imprinting.
      Mutations and epimutations in imprinted genes can give rise to genetic and
      epigenetic phenotypes, respectively; uniparental disomy and imprinting defects
      represent epigenetic disease phenotypes. There are also genetic disorders that
      affect chromatin structure and remodeling. These disorders can affect chromatin
      in trans or in cis, as well as expression of both imprinted and nonimprinted
      genes. Data from Angelman and Beckwith-Wiedemann syndromes and other disorders
      indicate that a monogenic or oligogenic phenotype can be caused by a mixed
      epigenetic and genetic and mixed de novo and inherited (MEGDI) model. The MEGDI
      model may apply to some complex disease traits and could explain negative results
      in genome-wide genetic scans.

PMID- 15485355
TI  - Mammalian circadian biology: elucidating genome-wide levels of temporal
      organization.
AB  - During the past decade, the molecular mechanisms underlying the mammalian
      circadian clock have been defined. A core set of circadian clock genes common to
      most cells throughout the body code for proteins that feed back to regulate not
      only their own expression, but also that of clock output genes and pathways
      throughout the genome. The circadian system represents a complex multioscillatory
      temporal network in which an ensemble of coupled neurons comprising the principal
      circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus is
      entrained to the daily light/dark cycle and subsequently transmits synchronizing
      signals to local circadian oscillators in peripheral tissues. Only recently has
      the importance of this system to the regulation of such fundamental biological
      processes as the cell cycle and metabolism become apparent. A convergence of data
      from microarray studies, quantitative trait locus analysis, and mutagenesis
      screens demonstrates the pervasiveness of circadian regulation in biological
      systems. The importance of maintaining the internal temporal homeostasis
      conferred by the circadian system is revealed by animal models in which mutations
      in genes coding for core components of the clock result in disease, including
      cancer and disturbances to the sleep/wake cycle.

PMID- 15485362
TI  - Response from the Australian Medical Association.

PMID- 15485361
TI  - A response to the Australian Health Care Agreements series.

PMID- 15485363
TI  - A private hospitals perspective.

PMID- 15485364
TI  - A comment on the response from Graham Wright.

PMID- 15485365
TI  - A response to the Australian Health Care Agreements series.

PMID- 15485366
TI  - A comment on the response from Graham Wright.

PMID- 15485367
TI  - Lessons from the inquiry into Obstetrics and Gynaecology services at King Edward
      Memorial Hospital 1990-2000.
AB  - The Douglas Inquiry investigated the Obstetrics and Gynaecological services at
      King Edward Memorial Hospital from 1990-2000. Performance deficiencies were
      identified at state, board and hospital level contributing to poor outcomes for
      women, babies and families. The Inquiry raises important issues about clinical
      governance, leadership and culture, accountability and responsibility, safety and
      quality systems, staff support and development, and concern for patients and
      their families. The King Edward, Bristol and Royal Melbourne Hospital inquiries
      reveal important similarities and key lessons for governments, health care
      leaders and providers. The health care industry must ensure effective clinical
      governance supporting a culture of inquiry and open disclosure, and must build
      rigorous systems to monitor and improve health care safety and quality.

PMID- 15485368
TI  - Commentary on the King Edward Inquiry: every defect a treasure.

PMID- 15485369
TI  - Commentary on the King Edward Inquiry: perspectives from the Chair, Australian
      Council for Safety and Quality in Health Care.

PMID- 15485370
TI  - Commentary on the King Edward Inquiry: lessons we fail to learn.

PMID- 15485371
TI  - Commentary on the King Edward Inquiry: coming soon to a theater near you.

PMID- 15485372
TI  - An audit of the use of epidural injections for back pain and sciatica.
AB  - An audit was conducted to determine if epidural injections for back pain and
      sciatica were practised in accordance with guidelines prescribed by the National
      Health and Medical Research Council (NHMRC). More than 80% of injections were
      used for conditions for which they were not indicated, and which the NHMRC
      considers experimental. Most commonly, epidural injections afforded no benefit to
      the patients, yet were often repeated. In no instance was informed consent
      recorded as recommended by the NHMRC. The practice of epidural injections is
      dissonant both with the evidence-based literature and with recommended
      guidelines, and squanders both financial and professional resources.

PMID- 15485373
TI  - Integrated services pathways (ISP): a best practice model.
AB  - Under the National Demonstration Hospitals Program, Phase 3 (NDHP3), Flinders
      Medical Centre (FMC) developed a best practice model for integrating acute care
      services with primary and community services. The project methodology included
      the examination of existing literature, involvement of consumers and other key
      stakeholders and the application of contemporary change and project management
      practices. Common elements were identified from four NDHP3 clinical service
      enhancement projects--aged care, cardiac surgical gastroenterology and
      orthopaedic services. The generic elements were transferred to the model. FMCs
      approach focused on developing a generic model that could be applied to clinical
      programs in a range of acute care settings. Although a number of barriers were
      encountered, the NDHP3 experience has shown that integration can be improved at
      the clinical program level without changing financial and management structures.

PMID- 15485374
TI  - Why outpatients fail to attend their scheduled appointments: a prospective
      comparison of differences between attenders and non-attenders.
AB  - Outpatient departments lie at a critical interface between primary care and acute
      services. Increasing pressure to ensure efficient and effective health care
      delivery has resulted in outpatient departments investigating ways to minimise
      the number of patients failing to attend their scheduled clinic appointments.
      Failure to attend (FTA) is an expensive and persistent problem worldwide with
      rates of between 5-39% reported in the literature. Similar FTA rates have also
      been detected in the Australian context. This study was undertaken to further
      investigate the reasons for FTA by conducting a prospective comparison of 100
      patients who attended their outpatient appointment with 100 patients who did not
      attend. Discriminant function analysis revealed that the major reason for non
      attendance was the patients' opinion about the difficulty in getting to the
      hospital. Previous non-attendance was found to be the strongest predictor of
      future FTA behaviour. A number of operational and system recommendations are made
      that based on the results, which may assist management to develop interventions
      to improve attendance rates.

PMID- 15485375
TI  - The transition from paediatric to adult health care services for young adults
      with a disability: an ethical perspective.
AB  - Young children with disabilities and their carers or parents tend to form a long
      term dependent relationship with a paediatrician throughout childhood. At some
      stage when the young person with a disability reaches early adulthood, the
      relationship is severed. This paper draws upon recent research undertaken by the
      authors that describes the difficulties experienced by young people with
      disabilities as they go through the transition from paediatric care to adult
      mainstream health care services. The purpose of this article is to present the
      argument that the dependent, paternalistic relationship that tends to exist
      between young people with disabilities (and/or their carers) and paediatricians
      throughout childhood does not facilitate the successful negotiation of adult
      mainstream health care services, nor optimally promote the well-being of these
      young people with disabilities. It is proposed that the promotion of autonomy (or
      self-determination) via a well planned transition program will increase the
      likelihood that young adults with disabilities and/or their carers will be
      empowered to successfully negotiate the current mainstream health care system in
      Australia, and will enhance the well-being of young adults with disabilities.

PMID- 15485376
TI  - A comparison of two measures of hospital foodservice satisfaction.
AB  - There are few published papers on patient satisfaction with food or nutrition
      services in either acute or chronic health care settings. The aim of this study
      was to evaluate two questionnaires for measuring patient satisfaction with
      hospital foodservice, the "Parkside Inpatient Questionnaire" and the "Wesley
      Hospital Foodservice Patient Satisfaction Questionnaire". Data were collected
      from 540 patients at a Queensland Public Hospital. Results indicated the Wesley
      Hospital Foodservice Patient Satisfaction Questionnaire obtained more positive
      patient feedback and was more reliable at measuring patient satisfaction (is
      porportional to = 0.89) than the Parkside Inpatient Questionnaire (is
      porportional to = 0.75), thus it is a more effective foodservice quality
      management tool.

PMID- 15485377
TI  - Hospital health care worker (HCW) vaccination coverage after implementation of an
      HCW vaccination policy.
AB  - The purpose of this study was to assess knowledge, attitudes, practices, and self
      reported vaccination status of HCWs at a tertiary Australian hospital, one year
      after implementation of a HCW vaccination policy. Two cross-sectional telephone
      surveys were conducted with HCWs at the hospital prior to and one year after HCW
      vaccination policy implementation. There was a 95% (272/287) response rate from
      eligible HCWs in the follow-up survey. Despite 96% (260/272) of HCWs indicating a
      willingness to update their vaccination status, only 24% (65/272) reported being
      fully vaccinated. Successful policy implementation requires adequate resource
      allocation and organisational commitment. Ongoing evaluation can inform the
      success of this process.

PMID- 15485378
TI  - Violence in the workplace: awareness and prevention.
AB  - Occupational violence is of growing interest to both individuals and
      organisations in the health field. Not surprisingly, staff who work directly on
      the front line are more vulnerable to episodes of physical violence from the
      general public. However, violence manifests in a number of ways, and any person
      in the workplace can experience it at anytime. Occupational violence should be
      viewed as an event to be identified, understood and managed, with a consequent
      need to identify types of violence in order to provide policy direction and
      preventive strategies to enhance workplace safety. Violence cannot be totally
      prevented but the risk of violence and its negative impacts on the individual can
      be reduced with carefully considered planningand swift action following a violent
      event. This paper reports various types of violence, the magnitude of the problem
      and who is at risk. Policy initiatives are suggested and methods of prevention
      discussed.

PMID- 15485379
TI  - Medical students' and GP registrars' accommodation needs in the rural community:
      insight from a Victorian study.
AB  - Medical education in Australia is currently entering a new era, including support
      for the significant extension of medical students and general practitioner (GP)
      registrars' training programs in rural communities. This commitment to rural
      medical student and general practitioner recruitment and retention has made the
      provision of accommodation in rural communities a vital issue. This study has
      found that approximately half of all medical students on placement with rural GPs
      are currently accommodated with their GP supervisor or with other practice staff.
      This is a burden for many GPs and when the anticipated increase in the frequency
      and length of rural placements occurs what is currently a burden will become
      unsustainable. The changing gender and cultural demographics of medical students
      and rural general practitioners will also contribute to stresses on this
      accommodation system. It is important to have a systematic approach towards more
      appropriate and sustainable models of accommodation for both medical students and
      GP registrars.

PMID- 15485380
TI  - A comparison of health insurance in Slovenia and Croatia.
AB  - Before Croatia and Slovenia became independent in 1991, they had similar health
      systems. They have generally taken the same reform path since then, but have also
      travelled in opposite directions on occasions. Of particular relevance here, both
      countries established quasi-government agencies to administer a new national
      scheme of compulsory health insurance in 1993. However, Slovenia's compulsory
      scheme involved much larger copayments, and a parallel voluntary insurance scheme
      was created mainly to cover them. In 2002, Croatia increased copayments and
      introduced a voluntary insurance scheme almost identical to that of Slovenia's.
      To complete the circle, Slovenia has announced it intends to abandon the use of
      voluntary insurance for copayments, and reduce the level of copayments for its
      compulsory scheme. This paper describes and compares the two insurance systems,
      and I argue that there has been considerable success in difficult circumstances.
      However, the experiences reinforce aspects of design that seem to be generally
      relevant: the need to make use of consumers' informed opinions, to recognise and
      then redress a lack of experience of optional approaches among many of those
      making decisions about health insurance, to define and apply a rigorous
      evaluation framework that includes estimating peoples total costs for health
      care, to emphasise the long term, to identify and ensure there is transparency of
      vested interests, and to use the financial power of the dominant government
      insurer to encourage and reward improvements in clinical practice.

PMID- 15485381
TI  - Factors influencing women's use of health services for sexually transmitted
      infections in eastern Nepal.
AB  - This paper explores low levels of women's health service utilization for Sexually
      Transmitted Infections (STIs) in Nepal. We interviewed 120 women individually and
      53 in focus groups. Predictors of lower utilisation were self-medication,
      consultation with faith healers, inadequate knowledge of STIs, belief about
      causes, fear, social taboos and stigmatisation, womens secondary status, and
      presence of male health professionals. Results indicate the importance of peoples
      belief in their decisions about health care. Strategies to improve access to
      health services in Nepal should systematically investigate the role of all these
      factors to improve access to and utilisation of health services for STIs.

PMID- 15485382
TI  - Community involvement in health in Mongolia: hospital boards and other
      participatory structures.
AB  - Under the Soviet central planning model that operated until 1990, the Mongolian
      population had little or no involvement in decision-making about health care. As
      part of overall health sector reform in Mongolia, hospital boards have been
      established, with significant community representation, to guide strategic and
      financial management and to assist in developing services according to community
      needs and expectations. We discuss experiences, and steps taken to resolve
      initial problems. We also describe other more recent participatory models
      including the family group practice initiative which involves the community
      choosing their doctor, community management of revolving drug finds,
      establishment of community health volunteer networks, and the governments
      information campaign strategy on the reforms. The community participation models
      in Mongolia are part of an ongoing process of openness and emphasise the
      commitment to change in that country. We argue that these experiences have the
      potential to guide and inform similar measures in other transitional countries.

PMID- 15485383
TI  - Innovations in aged care: study tours for Japanese health professionals.
AB  - Australian health care management is of increasing interest to Asian
      organisations, and there have been many advances in the conduct of informative
      tours. Points to consider when conducting such tours for Japanese visitors are
      described under the mnemonic STUDY TOURS: Specifications, Translation,
      Understanding culture, Delivering education, Yen, Timing, Organisation, Unique
      needs, Residents' values and Safety.

PMID- 15485384
TI  - Information technology creeps into rural general practice.
AB  - This study looked at the effect of information technology on rural medical
      practice. Eight GPs in rural medical practice in Victoria were interviewed, and
      World Wide Web sites were accessed for information relevant to the rural GPs use
      of information technology. The results indicated that rural GPs are developing
      their use of information technology according to their needs. The use of
      information technology is changing the nature of rural medical practice, and
      bringing more support and information to rural GPs. However, some of the
      technologies now available are of little perceived use to the GPs, and GPs with
      good support staff are better able to take advantage of the technology than GPs
      with little or inadequate support. The findings of this study have implications
      for policies being implemented to increase the availability of information
      technology to support rural health care.

PMID- 15485385
TI  - Accessing health information in a hospital setting: a consumer views study.
AB  - Meeting consumers' needs for health information is an important role for all
      health professionals. A Consumer Views Study was conducted at Flinders Medical
      Centre (FMC) to ensure strategies for improving access to health information for
      staff and consumers were congruent with consumers' views. Semi-structured
      questionnaires were completed by 100 consumers of FMC services. A key finding was
      the strong preference consumers have for accessing health information through
      staff members, which confirms the important part that education plays in
      information provision. A concern was that less than half of the participants were
      provided with written information. This could be indicative of the difficulties
      staff have in accessing health information to provide to consumers. Results also
      showed the important role General Practitioners (GPs) have in providing health
      information to consumers. Findings have helped shape strategies that focus on
      coordinated electronic access to quality health information, which will support
      staff in accessing and providing health information to consumers, and improve
      direct access to health information for consumers.

PMID- 15485386
TI  - Development and evaluation of a consumer's guide to residential aged care.
AB  - This three-phase study aimed to develop and evaluate an information guide for
      potential consumers of residential aged care. Phase 1 consisted of a series of
      six focus groups with 41 seniors to determine the information needs of potential
      consumers. Phase 2 comprised a 2 round Delphi survey in which a panel of 10
      industry stakeholders prioritised the themes identified by the focus groups.
      Phase 3 consisted of a pilot test and evaluation of the prototype information
      booklet by 19 seniors and their families. A feature of the guide is that its
      contents were identified by seniors themselves as information they wanted to know
      about residential care.

PMID- 15485387
TI  - Health care leadership in an age of change.
AB  - This study examined the leadership practices of a sample of network and hospital
      administrators in metropolitan Victoria, Australia. It was undertaken in the mid
      1990s when the State Liberal-National (Coalition) Government in Victoria
      established Melbourne's metropolitan health care networks. I argue that
      leadership, and the process of leading, contributes significantly to the success
      of the hospital in a time of turmoil and change. The sample was taken from the
      seven health care networks and consisted of 15 network and hospital
      administrators. Bolman and Deal's frames of leadership--structural, human
      resource, political and symbolic--were used as a framework to categorize the
      leadership practices of the administrators. The findings suggest a preference for
      the structural frame--an anticipated result, since the hospital environment is
      more conducive to a style of leadership that emphasizes rationality and
      objectivity. The human resource frame was the second preferred frame, followed by
      the political and symbolic. These findings suggest that network and hospital
      administrators focus more on intellectual than spiritual development, and perhaps
      this tendency needs to be addressed when educating present and future hospital
      leaders.

PMID- 15485388
TI  - Community management structures to promote health.
AB  - This article describes key requirements of effective health service management
      that emerge from a review of Australian developments in the respective roles of
      government and the market. From a public interest perspective, community and
      industry ownership and management of funds appear superior to market-driven
      health management approaches. The clear separation of public interest-based
      policy and administrative functions is vital for effective fund management.
      Greater transparency, more community input to broadly planned service delivery,
      casemix funding systems and better outcome data are required to tap the potential
      benefits of this policy-led model. A pooled funding approach to service provision
      may assist regional communities achieve their health aims, and the service
      breadth and flexibility which appear to be necessary to support health and
      related regional goals.

PMID- 15485389
TI  - Beyond organisational design: moving from structure to service enhancement.
AB  - The Australian health care industry prior to the 1990s was notable for its
      relative stability and uniformity in relation to organisational design. Since
      then, new organisational designs have proliferated and a diversity of approaches
      is evident. The new fluidity in organisational design is particularly evident
      amongst the allied health professions. The aim of this paper is two-fold.
      Firstly, to summarise recent changes in organisational design as they relate to
      the allied health professions and secondly, to move beyond design issues to focus
      on service level enhancement in an organisational change context. This later aim
      is achieved by presenting data from an in-depth study of one institutions
      experience with wide-ranging organisational reforms. The recent formation of the
      National Allied Health Organisational Structures Network (NAHOSN) has given
      energy to the impetus of placing a research-based framework around the change
      experiences reported by Allied Health groups. An objective of the network is to
      foster research, rather than rely on commentary and anecdote, in the often highly
      contested arena of organisational design and reform.

PMID- 15485390
TI  - The causes and consequences of nursing shortages: a helicopter view of the
      research.
AB  - In Australia, as in most industrialised countries, there is an acute shortage of
      registered nurses. While there are numerous research reports emanating from
      Canada, the United States and Great Britain that provide insight into reasons for
      this shortage, little comparable work has been undertaken in Australia. This
      paper presents an overview of the complex interlinking set of factors which cause
      or are the consequences of nursing shortages including lifestyle preferences,
      workforce composition, quality of work life and workload and the impact of
      organisational change and altered management practices. It is important that
      managers in Australian health care settings understand these issues in order to
      work towards developing sustainable solutions for retention.

PMID- 15485391
TI  - A study of quality management practices in nursing in universities in Australia.
AB  - In Australia, the traditional Quality Assurance approach used in the hospital
      setting has played an important role in nursing practice. During the past decade,
      nurses have begun making a paradigm shift from Quality Assurance to Total Quality
      Management but scant attention has been paid to quality management practices in
      nursing in the higher education sector. This paper reports on a quantitative
      study examining the perceptions of nurse academics to the applicability of TQM to
      nursing in universities. The findings identified how TQM could be applied to suit
      the nursing culture in the higher education sector.

PMID- 15485392
TI  - Casualisation of the nursing workforce in Australia: driving forces and
      implications.
AB  - This article provides an overview of the extent of casualisation of the nursing
      workforce in Australia, focusing on the impact for those managing the system. The
      implications for nurse managers in particular are considerable in an industry
      where service demand is difficult to control and where individual nurses are
      thought to be increasingly choosing to work casually. While little is known of
      the reasons behind nurses exercising their preference for casual work
      arrangements, some reasons postulated include visa status (overseas trained
      nurses on holiday/working visas); permanent employees taking on additional shifts
      to increase their income levels; and those who elect to work under casual
      contracts for lifestyle reasons. Unknown is the demography of the casual nursing
      workforce, how these groups are distributed within the workforce, and how many
      contracts of employment they have across the health service--either through
      privately managed nursing agencies or hospital managed casual pools. A more
      detailed knowledge of the forces driving the decisions of this group is essential
      if health care organisations are to equip themselves to manage this changing
      workforce and maintain a standard of patient care that is acceptable to the
      community.

PMID- 15485393
TI  - The provision and utilisation of casemix and demographic data by nursing managers
      in seven hospitals.
AB  - The role of the nursing manager has evolved from clinician and bed manager to one
      with greater accountability for evidence based practice, benchmarking and more
      recently, budget liability. Casemix data are widely believed to be a means of
      providing essential information for effective decision making and financial
      management but have not been widely utilised by nursing managers (Diers & Bozzo,
      1999). This paper will report the results of a survey of nursing managers in
      seven hospitals within a metropolitan area health service. The hospitals include
      tertiary referral hospitals, specialist public hospitals and an affiliated public
      hospital for aged care and rehabilitation services. The survey sought to
      establish what casemix and related data were provided to nurse managers, who
      provided these data and how supplied data were utilised by the nurse managers.
      Results demonstrated that the majority of nursing managers surveyed received
      minimal (if any) casemix and/or demographic data on a routine basis. Some were
      provided with data in response to specific requests. The information that was
      provided varied both within and across hospitals, and no consistent methods of
      data distribution were available. Few nursing managers believed that the
      information provided aided their decision-making processes partly due to the
      minimalist nature of provided data while some nursing managers demonstrated a
      lack of understanding of the potential benefit of casemix data as a resource to
      support management decision making.

PMID- 15485394
TI  - Erratum: Waiting time information services: how well do different statistics
      forecast a patient's wait?

PMID- 15485395
TI  - The BIR domain of IAP-like protein 2 is conformationally unstable: implications
      for caspase inhibition.
AB  - Several IAP (inhibitor of apoptosis) proteins regulate cell fate decisions, and
      the X-linked IAP (XIAP) does so in part by inhibiting caspases, proteases that
      execute the apoptotic pathway. A tissue-specific homologue of XIAP, known as ILP2
      (IAP-like protein 2), has previously been implicated in the control of apoptosis
      in the testis by direct inhibition of caspase 9. In examining this protein we
      found that the putative caspase 9 interaction domain is a surprisingly weak
      inhibitor and is also conformationally unstable. Comparison with the equivalent
      domain in XIAP demonstrated that the instability is due to the lack of a linker
      segment N-terminal to the inhibitory BIR (baculovirus IAP repeat) domain. Fusion
      of a 9-residue linker from XIAP to the N-terminus of ILP2 restored tight caspase
      9 inhibition, dramatically increased conformational stability and allowed
      crystallization of the ILP2 BIR domain in a form strikingly similar to the XIAP
      third BIR domain. We conclude that ILP2 is an unstable protein, and cannot
      inhibit caspase 9 in a physiological way on its own. We speculate that ILP2
      requires assistance from unidentified cellular factors to be an effective
      inhibitor of apoptosis in vivo.

PMID- 15485398
TI  - Proteinuria and hypertensive nephrosclerosis in African Americans.
AB  - Proteinuria is a known risk factor for both renal disease progression and
      cardiovascular morbidity and mortality in hypertensive populations. African
      Americans are among the highest risk groups for development of renal disease in
      the setting of hypertension and suffer a disproportionate burden of end-stage
      renal disease attributed to hypertension. Population-based studies indicate that
      African Americans have higher rates of albuminuria compared to non-African
      Americans in part due to higher rates of hypertension and diabetes in African
      Americans as compared to non-Hispanic whites for example. The African American
      Study of Kidney Disease and Hypertension (AASK) Trial was a prospective long-term
      clinical trial that examined the effect of aggressive blood pressure lowering
      versus usual blood pressure lowering in three different classes of
      antihypertensives on renal outcomes in approximately 1200 African Americans with
      hypertensive nephrosclerosis. Two thirds of trial participants had < 300 mg
      protein, and one third had > or = 300 mg of protein in a 24-hour urine specimen
      at baseline. Those with > 300 mg protein excretion compared to those with < 300
      mg protein excretion at baseline had more rapid decline in renal function and
      ESRD events. Moreover, lower levels of proteinuria than previously thought may be
      important for identifying those at higher risk for kidney disease progression.
      The AASK cohort study, a follow-up to the trial, is now underway. The longer term
      follow-up will provide new insights into proteinuria and other risk factors for
      progression of kidney disease in hypertensive nephrosclerosis.

PMID- 15485396
TI  - Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor:
      implications for Smac-dependent anti-apoptotic activity of ML-IAP.
AB  - ML-IAP (melanoma inhibitor of apoptosis) is a potent anti-apoptotic protein that
      is strongly up-regulated in melanoma and confers protection against a variety of
      pro-apoptotic stimuli. The mechanism by which ML-IAP regulates apoptosis is
      unclear, although weak inhibition of caspases 3 and 9 has been reported. Here,
      the binding to and inhibition of caspase 9 by the single BIR (baculovirus IAP
      repeat) domain of ML-IAP has been investigated and found to be significantly less
      potent than the ubiquitously expressed XIAP (X-linked IAP). Engineering of the ML
      IAP-BIR domain, based on comparisons with the third BIR domain of XIAP, resulted
      in a chimeric BIR domain that binds to and inhibits caspase 9 significantly
      better than either ML-IAP-BIR or XIAP-BIR3. Mutational analysis of the ML-IAP-BIR
      domain demonstrated that similar enhancements in caspase 9 affinity can be
      achieved with only three amino acid substitutions. However, none of these
      modifications affected binding of the ML-IAP-BIR domain to the IAP antagonist
      Smac (second mitochondrial activator of caspases). ML-IAP-BIR was found to bind
      mature Smac with low nanomolar affinity, similar to that of XIAP-BIR2-BIR3.
      Correspondingly, increased expression of ML-IAP results in formation of a ML-IAP
      Smac complex and disruption of the endogenous interaction between XIAP and mature
      Smac. These results suggest that ML-IAP might regulate apoptosis by sequestering
      Smac and preventing it from antagonizing XIAP-mediated inhibition of caspases,
      rather than by direct inhibition of caspases.

PMID- 15485399
TI  - The effects of valsartan on the accumulation of circulating and renal advanced
      glycation end products in experimental diabetes.
AB  - BACKGROUND: Blockade of the RAS with the ACE inhibitor ramipril prevents the
      accumulation of advanced glycation end products (AGEs) in experimental diabetes.
      Although AT1 receptor antagonists may inhibit AGE formation in vitro, their
      effect in normotensive animals with type 1 diabetes has not been established.
      METHODS: Streptozotocin-induced diabetic and control animals were randomized
      (N=10/group) to receive the AT1 antagonist valsartan at a dose of 30 mg/kg/day by
      oral gavage for 24 weeks, or no intervention. Renal and plasma AGE accumulation
      was correlated with renal functional parameters. RESULTS: Valsartan reduced the
      albumin excretion rate consistent with its renoprotective effects. Renal and skin
      collagen accumulation of the non-fluorescent AGE carboxymethyllysine (CML) were
      increased in animals with diabetes, but normalized following treatment with
      valsartan. Renal fluorescence and skin collagen pentosidine levels were also
      increased by diabetes. However, valsartan only provided a modest attenuation of
      these parameters. In addition, diabetes was associated with increased plasma
      fluorescence, which was unaffected by AT1 antagonism. CONCLUSION: Renoprotective
      doses of valsartan are associated with a significant reduction in the
      accumulation of tissue and plasma CML. These effects were not the same for all
      AGEs, suggesting combination approaches will be required to optimize
      renoprotection in diabetes.

PMID- 15485400
TI  - Beneficial impact on cardiovascular risk factors by dual blockade of the renin
      angiotensin system in diabetic nephropathy.
AB  - BACKGROUND: Patients with diabetic nephropathy have a high risk of cardiovascular
      disease and end-stage renal disease. Dual blockade of the renin-angiotensin
      system (RAS) with both ACE inhibitors (ACE-I) and angiotensin II receptor
      blockers may offer therapeutic advantages. METHODS: Based on three double-blind
      randomized cross-over trials, we analyzed the short-term effects of dual blockade
      of the RAS on cardiovascular surrogate end points in 51 type 1 diabetic patients
      with diabetic nephropathy. RESULTS: Compared to ACE-I, dual blockade of the RAS
      decreased albuminuria 37% from 558 mg/24 hour, and lowered 24-hour blood pressure
      7/5 mm Hg from 137/76 mm Hg (P < 0.01). In addition, dual blockade lowered total
      and LDL-cholesterol 0.3 from 5.4 mmol/L and 3.1 mmol/L, respectively (P < or =
      0.01). The antialbuminuric response to dual blockade of the RAS was influenced by
      the insertion (I)/deletion (D) polymorphism in the ACE gene. CONCLUSION: Dual
      blockade of the RAS may offer additional cardiovascular and renal protection in
      type 1 diabetic patients with diabetic nephropathy. Determination of the ACE/ID
      genotype may help identify patients particularly sensitive to such therapy.

PMID- 15485401
TI  - Cardiovascular risk in chronic kidney disease.
AB  - National Kidney Foundation guidelines define chronic kidney disease (CKD) as
      persistent kidney damage (confirmed by renal biopsy or markers of kidney damage)
      and/or glomerular filtration rate (GFR) <60 mL/min/1.73m2 for greater than three
      months. Patients with CKD experience higher mortality and adverse cardiovascular
      (CV) event rates, which remains significant after adjustment for conventional
      coronary risk factors. This progressive CV risk associated with worsening renal
      function may be explained by other factors that become increasingly important
      with renal decline. In this regard, more investigation of nonconventional factors
      that have received a lot of attention includes associations with inflammation,
      albuminuria, reduced vascular compliance, and homocysteine. In addition,
      individuals with CKD encounter the problem of "therapeutic nihilism," in which
      there is a lack of appropriate risk factor modification and intervention, despite
      established awareness of their high cardiovascular risk. Several studies suggest
      that these individuals derive as much, if not more, benefit from evidence-based
      cardiovascular therapies and strategies. Greater educational efforts are needed
      to reduce this therapeutic gap.

PMID- 15485402
TI  - Framingham score and microalbuminuria: combined future targets for primary
      prevention?
AB  - BACKGROUND: Risk assessment is the cornerstone of primary prevention of
      cardiovascular disease. Our objective was to evaluate the prognostic value of the
      Framingham score in microalbuminuric subjects without a history of cardiovascular
      disease and whether this risk score can predict the benefit of treatment with
      fosinopril or pravastatin. METHODS: Subjects were randomized to fosinopril 20 mg
      or matching placebo, and to pravastatin 40 mg or matching placebo (mean age 51 +/
      12 years, 65% men, N = 830). Prediction of 10-year risk for coronary heart
      disease by the Framingham score was performed using the risk factor categories
      with LDL cholesterol. RESULTS: Albuminuria was correlated with Framingham score
      at baseline (P < 0.001). In the population with a Framingham risk score <20%,
      both albuminuria and Framingham risk score were independent predictors of the
      primary end point. A two-fold increase of albuminuria or the Framingham risk
      score was associated with a hazard ratio of 1.60 (95% CI 1.10-2.31), P = 0.013
      and 3.00 (95% CI 1.40-6.44), P = 0.005, respectively. In contrast to fosinopril,
      pravastatin showed a significant beneficial effect on Framingham risk score after
      4 years of follow-up (P < 0.001). Furthermore, the observed absolute risk
      reduction in cardiovascular events was greater than calculated by the Framingham
      risk score. CONCLUSION: The Framingham score is useful in microalbuminuric
      subjects as a prognostic tool. In addition, when considering the risk score as a
      target of intervention, the beneficial effects of therapies might be
      underestimated. Combining the Framingham score with the level of urinary albumin
      excretion is suggested as a primary prevention strategy with higher efficiency.

PMID- 15485403
TI  - Losartan and the United States costs of end-stage renal disease by baseline
      albuminuria in patients with type 2 diabetes and nephropathy.
AB  - BACKGROUND: Type 2 diabetes is the leading cause of end-stage renal disease
      (ESRD). The Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist
      Losartan (RENAAL) study provided the opportunity to estimate costs associated
      with ESRD by baseline albuminuria from a United States perspective. METHODS:
      Costs for ESRD in patients with diabetes were estimated by baseline albuminuria
      using the U.S. Renal Data System by using the number of days each patient
      experienced ESRD and the daily estimated U.S. cost of ESRD. RESULTS: The losartan
      based antihypertensive therapy group experienced a 28.6% (P=0.002) reduction in
      the risk of the development of ESRD compared with placebo-based conventional
      antihypertensive therapy. The previously estimated annual ESRD-related cost
      saving in the losartan group was 5,144 dollars (95% CI 1,701-8,586 dollars,
      P=0.003) at 3.5 years. With the cost of losartan, the net savings in the losartan
      group was estimated at 3,522 dollars (143-6,900 dollars, P=0.041) by 3.5 years.
      More ESRD-free days were observed and reduced ESRD costs estimated with losartan
      based treatment over all levels of baseline albuminuria. CONCLUSION: Treatment
      with losartan in patients with type 2 diabetes and nephropathy in the RENAAL
      study not only reduces the incidence of ESRD, but is also estimated from a U.S.
      perspective to result in substantial cost savings over the 3.5-year duration of
      the trial across all levels of baseline albuminuria.

PMID- 15485404
TI  - Health economics studies assessing irbesartan use in patients with hypertension,
      type 2 diabetes, and microalbuminuria.
AB  - Two studies comparing the cost-effectiveness of irbesartan to similar blood
      pressure control with standard antihypertensive medications (excluding
      angiotensin-converting enzyme inhibitors and other angiotensin receptor blockers)
      in treatment of patients with hypertension, type 2 diabetes, and microalbuminuria
      have been published to date; one in a United States setting, the other in a
      Spanish setting. Both studies were based on a Markov-based Monte Carlo simulation
      model, with the effects of irbesartan or standard blood pressure control taken
      from the Irbesartan Reduction of Microalbuminuria-2 (IRMA-2) and the Irbesartan
      in Diabetic Nephropathy Trial (IDNT) clinical trials. In both Spanish and U.S.
      settings, irbesartan was projected to delay the onset of end-stage renal disease
      (ESRD), reduce the cumulative incidence of ESRD, increase life expectancy, and
      reduce overall direct medical costs. Irbesartan treatment of patients with type 2
      diabetes, hypertension, and microalbuminuria may lead to major improvements in
      long-term patient outcomes, with substantial cost savings as an added bonus to
      third party payers.

PMID- 15485405
TI  - Inclusion of albumin as a target in therapy guidelines: guidelines for chronic
      kidney disease.
AB  - Slowing the rate of progression of chronic kidney disease (CKD) as a fundamental
      management goal has been greatly assisted by the development of clinical practice
      guidelines under the aegis of the National Kidney Foundation, through the K/DOQI
      process. Reductions in urinary protein and albumin excretion play important roles
      in these treatment strategies, with numerous studies describing short- and long
      term successes in these endeavors. These approaches may also reduce the risks of
      cardiovascular and cerebrovascular morbidity and mortality, and of developing new
      onset diabetes mellitus. With enhanced sensitivity assays for urinary albumin,
      and the near-term availability of point-of-service testing, we will have the
      opportunity to address reduction of urinary albumin excretion as a defined goal
      and critical element in management of CKD. Carefully conducted clinical trials
      are needed to establish the utility of these assays, and to define optimal
      strategies for reducing urinary albumin excretion. With the successful outcomes
      of these studies, the reduction of urinary albumin excretion will receive its due
      emphasis in the management of patients with CKD.

PMID- 15485406
TI  - Inclusion of albuminuria in hypertension and heart guidelines.
AB  - The current recommendations by all United States guideline committees, including
      the American Diabetes Association and the JNC 7, include screening for
      microalbuminuria in those with diabetes or evidence of kidney disease, but not
      the general population. Internationally, both the Canadian and European
      Guidelines have concurred with this approach. This recommendation is due in part
      to the findings from long-term outcome studies that measurement of
      microalbuminuria, while a strong predictor of cardiovascular risk, fails to shows
      change in CV events if reduced. Unfortunately, this conclusion may be wrong
      because no randomized trial has examined the question of whether a reduction in
      microalbuminuria does correlate with a reduction in CV events. Thus, we don't
      know the answer to this question. Additionally, a recent cost-effective analysis
      was just published, suggesting it is not worth measuring urinary albumin because
      it is too expensive for the information obtained. Unfortunately, these
      conclusions were based on the same faulty logic that relates changes in
      microalbuminuria to cardiovascular events. It is clear that microalbuminuria is a
      cardiovascular risk factor, acknowledged by both the JNC 7 and the European
      Guidelines. Moreover, presence of microalbuminuria correlates strongly with
      elevated levels of C-reactive protein and abnormal vascular responsiveness to
      vasodilating stimuli. Thus, its presence indicates abnormal responses by vascular
      tissue, perhaps due to underlying inflammatory responses. Every clinical trial
      that has assessed changes in albuminuria as a secondary end point with clinical
      outcomes has shown a strongly positive correlation between reduction in
      albuminuria and greater protection of a given end organ; this effect is, in part,
      independent of blood pressure reduction. Thus, what is needed is a clinical trial
      in people at high cardiovascular risk, such as those in the INVEST or ALLHAT
      trials where the primary end point is change in albuminuria and its relationship
      to cardiovascular outcomes. Likewise, a cardiovascular primary end point could
      relate to the secondary end point of changes in microalbuminuria, and the latter
      powered appropriately to make stronger statements about albuminuria and
      cardiovascular outcomes. With this data, guidelines can then make much strong
      statements about intervention on this marker of risk.

PMID- 15485407
TI  - Albuminuria as a surrogate marker for drug development: a European Regulatory
      perspective.
AB  - Clinical trials with surrogate end points generally require smaller sample sizes
      and shorter duration than those with clinical outcomes. However, in practice,
      surrogate end points are likely to result in less comprehensive conclusions than
      'outcome' end points as they sometimes reflect only partial aspects of complex
      phenomena. A number of conditions help to establish the validity of a particular
      variable as predictive of clinical outcome. This article discusses to what extent
      albuminuria fulfills these requisites in two particular clinical scenarios:
      prevention of renal deterioration and prevention of cardiovascular disease.

PMID- 15485408
TI  - Which albumin should we measure?
AB  - Albumin circulates in the blood as a single homogeneous protein. During passage
      to the urine it can undergo configuration and digestive change, producing
      moieties not equally detected by the various methods currently routinely used for
      quantifying albuminuria. In normal urine, albumin is not the most common protein.
      In microalbuminuric states, detection techniques of great sensitively and
      specificity are required, looking for the whole molecule, immunoreactive
      moieties, peptide fragments, or all of these. We are unsure of the most accurate
      technique in terms of patient prognosis; accordingly, we must now ask "Which
      albumin should we measure?"

PMID- 15485409
TI  - An elevated urinary albumin excretion predicts de novo development of renal
      function impairment in the general population.
AB  - BACKGROUND: We questioned which factors determine the risk for developing renal
      function impairment. To that purpose, we studied the incidence of newly diagnosed
      impaired renal function (GFR <60 mL/min/1.73m2) in the PREVEND cohort (N=8592),
      which is enriched for the presence of albuminuria, and which was first studied in
      1997-1998. Of this cohort, 6894 subjects were studied again four years later.
      METHODS: Subjects with known renal disease, GFR <60 mL/min, missing GFR values,
      or sediment abnormalities at the first screening were excluded from the present
      analysis (N=872). We examined whether albuminuria is associated with the de novo
      development of an impaired renal function. GFR was 90.3 (SD 16.3) mL/min/1.73m2
      at baseline, and 11.6% of the subjects had an albuminuria of more than 30 mg/day.
      RESULTS: After a follow-up of four years, 253 subjects (4.2%) were found to have
      a GFR <60 mL/min/1.73m2. The subjects with newly diagnosed impaired GFR were
      older, had a higher blood pressure, serum cholesterol, plasma glucose, and
      urinary albumin excretion at the first examination, and had a lower GFR to start
      with than those with a GFR >60 at the second evaluation. Subjects with de novo
      impaired GFR had a comparable BMI and smoked less frequently compared with
      subjects with GFR >60. In multivariate analysis, urinary albumin excretion was
      independently predictive for the risk of developing an impaired GFR (P=0.001).
      CONCLUSION: Also in the general population, measurement of urinary albumin
      excretion may prove to be a valuable tool to detect subjects at risk for later
      development of renal failure, independent of the presence of other cardiovascular
      risk factors.

PMID- 15485410
TI  - Albuminuria, not only a cardiovascular/renal risk marker, but also a target for
      treatment?
AB  - Albuminuria has been identified as a marker for predicting both cardiovascular
      and renal risk. From normal to overt proteinuria levels, albuminuria shows a
      continuous marked increase in risk. This is independent of other well-known
      cardiovascular and renal risk markers and factors, such as blood pressure,
      cholesterol, smoking, overweight, and others. The predictive power is not only
      present in already diseased populations with either nondiabetic or diabetic renal
      disease, but also in hypertensive and even in otherwise healthy populations. New
      antihypertensive intervention strategies, such as angiotensin-converting enzyme
      (ACE) inhibitors and angiotensin II (Ang II) receptor-antagonists are claimed to
      have cardioprotective and renoprotective benefits that go beyond blood pressure
      control. Interestingly, these new therapeutic classes share the ability to lower
      urinary albumin excretion by an average of 40%, a characteristic that is not
      observed with the other antihypertensive drug classes. This short-term-induced
      antiproteinuric effect appears to predict the long-term cardiovascular and renal
      protection: the more albuminuria is lowered, the more that individual (or group)
      is protected. These data suggest that albumin is not only a risk marker for
      cardiovascular and or renal disease, but it may also be a useful target for
      therapy. Monitoring of albuminuria should be daily practice in subjects at risk
      for cardiovascular and renal disease. In addition to new clinical trials that
      prove that albumin can be targeted to obtain cardiovascular protection,
      guidelines should be made to help the physician in deciding how to measure
      albumin in the urine, what are normal levels, how to target "abnormal" levels,
      and how low we should go.

PMID- 15485411
TI  - Prevalence of albuminuria in Australia: the AusDiab Kidney Study.
AB  - BACKGROUND: Albuminuria is an important predictor of risk of progressive renal
      disease, cardiovascular disease, and mortality; however, the prevalence in the
      general population is not well defined. We determined estimates of the population
      prevalence and associations of microalbuminuria and macroalbuminuria in
      Australian adults; 11,247 Australians aged > or = 25 years living in 42 randomly
      selected population clusters were tested for albuminuria (spot urine
      albumin:creatinine (mg/mmol): normal < 3.4, microalbuminuria 3.4 to 34,
      macroalbuminuria > 34). METHODS: Prevalence of micro- and macroalbuminuria were
      assessed with age, sex, obesity, smoking, hypertension (> or = 140/90 mm Hg or
      known diagnosis on treatment), glucose metabolism status (WHO criteria according
      to fasting glucose and oral glucose tolerance test), ischemic heart and
      cerebrovascular disease, and low glomerular filtration rate (calculated
      glomerular filtration rate < 60 mL/min/1.73m2). RESULTS: Microalbuminuria and
      macroalbuminuria proteinuria were present in 6.0% and 0.6% of the population,
      respectively. The majority of subjects with microalbuminuria (64%) and
      macroalbuminuria (76%) had hypertension, and approximately half of those with
      albuminuria had abnormal glucose metabolism. Of all participants with
      microalbuminuria, 25.9% had normal blood pressure and glucose metabolism, and in
      this group, alternative associations of microalbuminuria included obesity
      (13.5%), smoking (20.7%), and low glomerular filtration rate (12.3%). CONCLUSION:
      Albuminuria is present in a small percentage of the general adult population, but
      is highly prevalent in subjects with hypertension and/or abnormal glucose
      metabolism. The majority of cases of microalbuminuria and macroalbuminuria in the
      general population are among those with hypertension.

PMID- 15485412
TI  - Albuminuria: marker or target in indigenous populations.
AB  - BACKGROUND: Australian Aborigines in remote areas are experiencing an epidemic of
      renal disease, type 2 diabetes, hypertension, and cardiovascular disease. Adult
      deaths are increased 3- to 6-fold, and renal failure more than 20-fold. Renal
      disease is marked by albuminuria. We describe its distributions and correlations
      in two remote communities in the Northern Territory. METHODS: Observations in
      Community 1 included a screen of 939 adult participants (18+ years, 90%
      recruitment), a treatment program, and 8 to 11 years of follow-up. In Community
      2, a screen of 259 people, or 60% of adults, included HbA1c, homocysteine, C
      reactive protein (CRP), CMV serology, and carotid intimal media thickness (CIMT).
      Albumin/creatinine ratio (ACR) was measured by immunoassay in g/mol on random
      urine, with microalbuminuria defined as 3.4 to 33, and overt albuminuria as ACR
      34+. RESULTS: Dipstick urine protein trace+ correctly classified 76% of people
      with ACR 3.4+, and dipstick protein 1+ correctly classified 82% of people with
      ACR 34+. ACR was stable to glucose loading and water diuresis in subsets of
      people in Community 1. ACR levels rose steeply with age. Rates of micro- and
      overt albuminuria in Community 1 were 28% and 21%, and in Community B were 31%
      and 13%. ACR correlated inversely with estimated glomerular filtration rate
      (GFR). ACR also correlated directly with weight, blood pressure, cholesterol,
      triglycerides, random glucose, HbA1c, homocysteine, and GGT levels, and inversely
      with HDL cholesterol. ACR correlated with skin sores, scabies, high titer
      antibodies to Helicobacter pylori, high-titer CMV antibodies, with CRP over a
      greatly elevated range and, inversely, with birth weight. Finally, ACR correlated
      with CIMT. Baseline ACR predicted loss of GFR over time. ACR 3.4+ predicted all
      cause and cardiovascular hospitalization, while ACR 34+ predicted all renal
      failure developing over 11 years and all-cause natural deaths and cardiovascular
      disease deaths. ACEi treatment for people with ACR 34+ reduced renal failure and
      natural deaths, but the hierarchical effect of higher ACRs within that group for
      renal and nonrenal deaths was maintained. CONCLUSION: Random urine ACR is a
      stable and robust marker of renal disease, which is multideterminant. A broad
      base of shared risk factors probably explains the simultaneous emergence of the
      excessive renal and nonrenal chronic disease morbidities from which these
      populations suffer. Thus, albuminuria is a unifying marker for the harmful
      effects of the spectrum of chronic disease, and perhaps beyond. Dipstick urine
      protein is a useful surrogate for ACR when resources are constrained and disease
      burdens high.

PMID- 15485413
TI  - Demographic and epidemiologic transition in the developing world: role of
      albuminuria in the early diagnosis and prevention of renal and cardiovascular
      disease.
AB  - The developing world is facing a real pandemic of renal and cardiovascular
      disease. With the decrease of infectious disease morbidity and mortality, and the
      exposure to more westernized life style, signs of increasing renal and
      cardiovascular disease is particularly shown in the tremendous rise in type 2
      diabetes and its sequelae. A group of doctors and scientists from all over the
      world have convened in Bellagio to halt this dramatic disease change and burden
      to the developing countries. They came to the conclusion that screening and
      treatment should clearly focus on cost-beneficial strategies, among which blood
      pressure and urinary albumin measurement, as well as effective and affordable
      treatment strategies to lower blood pressure and albuminuria, are essential.

PMID- 15485414
TI  - Albuminuria predicting outcome in diabetes: incidence of microalbuminuria in Asia
      Pacific Rim.
AB  - Microalbuminuria is not an unusual finding in the general population, even in
      individuals without diabetes, hypertension, or cardiovascular risk factors.
      Prevalence studies in the United States, such as NHANES III, reported an overall
      incidence of microalbuminuria in 22,244 patients, with and without diabetes, of
      7.8%. In those individuals with diabetes, the prevalence was 28.8%. Even in
      patients without diabetes, cardiovascular disease, or abnormal serum creatinine
      levels, the prevalence of microalbuminuria was still 5.1%. Similarly, a large
      Dutch study of 41,000 participants demonstrated a 7% incidence of
      microalbuminuria. In those individuals with diabetes, the microalbuminuria rate
      was 16%. Thus, in both the United States and Europe, prevalence studies indicate
      that microalbuminuria is not uncommon. In southeast Asia and the western Pacific,
      the incidence of type 2 diabetes is rapidly escalating. It is expected that by
      2025 the major prevalence of type 2 diabetes in the world will not be in North
      America or Europe but in Asia-Pacific Rim. Consequently, there is great interest
      in evaluating the incidence of microalbuminuria in this region. In the
      Microalbuminuria Prevalence Study (MAPS) the prevalence of macroalbuminuria was
      noted to be 18.8% and microalbuminuria 39.8% in a total of 6800 hypertensive
      diabetic adult patients from 10 Asian countries. Thus, there is important
      evidence that the substantial prevalence of microalbuminuria and macroalbuminuria
      in the Pacific region indicates an impending pandemic of diabetic cardiovascular
      and renal disease.

PMID- 15485415
TI  - Microalbuminuria, glycemic control, and blood pressure predicting outcome in
      diabetes type 1 and type 2.

PMID- 15485416
TI  - Microalbuminuria is associated with impaired brachial artery, flow-mediated
      vasodilation in elderly individuals without and with diabetes: further evidence
      for a link between microalbuminuria and endothelial dysfunction--the Hoorn Study.
AB  - BACKGROUND: Extensive endothelial dysfunction (i.e., affecting many aspects of
      endothelial function) has been hypothesized to explain why microalbuminuria (MA)
      is associated with cardiovascular disease risk. However, it is not clear whether
      MA is specifically associated with impaired endothelial nitric oxide (NO)
      synthesis in individuals without and with type 2 diabetes. METHODS: We did a
      population-based study in 645 individuals (mean age 68 years; 248 with normal
      glucose metabolism, 137 with impaired glucose metabolism, and 260 with type 2
      diabetes) and investigated associations of MA [present (urinary albumin
      creatinine ratio > or = 2 mg/mmol) versus absent, and in four categories (< 2, >
      or = 2 to 5, > or = 5 to 10, > or = 10 mg/mmol)] with ultrasonically measured
      brachial artery endothelium-dependent, flow-mediated (FMD; an estimate of
      endothelial NO synthesis) and endothelium-independent, nitroglycerin-induced
      vasodilation (NID). RESULTS: FMD was 0.12 mm in the presence of MA (N=93; 49 with
      diabetes), and 0.18 in its absence (P=0.002). After adjustment for age, sex,
      baseline arterial diameter, and other potential confounders, FMD was 0.038 mm
      (95% CI, 0.001 to 0.075) lower in the presence of MA (P=0.04), and decreased
      linearly across MA categories [by 0.027 mm (0.007 to 0.046) per category increase
      of MA; P=0.007]. NID was similar in individuals with and without MA. Results were
      similar in individuals without and with diabetes. CONCLUSION: Microalbuminuria is
      linearly associated with impaired endothelium-dependent, flow-mediated
      vasodilation in elderly individuals without and with diabetes. These findings
      support the concept that impaired endothelial nitric oxide synthesis plays a role
      in the association of microalbuminuria with cardiovascular disease risk.

PMID- 15485417
TI  - Effect of proteinuria and glomerular filtration rate on cardiovascular risk in
      essential hypertension.
AB  - Changes in renal function related with essential hypertension are associated with
      an elevated cardiovascular morbidity and mortality. Indices of altered renal
      function (e.g., microalbuminuria, increased serum creatinine concentrations,
      decrease in estimated creatinine clearance or GFR, and overt proteinuria) are
      independent predictors of cardiovascular morbidity and mortality. The Framingham
      Heart Study documented the relevance of proteinuria for cardiovascular prognosis
      in the community. The INSIGHT Study assessed the role of proteinuria as a risk
      factor in essential hypertension. The presence of proteinuria at baseline turned
      out to be a very potent predictor for the development of cardiovascular events
      and death in patients with essential hypertension and one or more associated
      cardiovascular risk factors. Recent data indicate that minor derangements of
      renal function, including proteinuria, are associated, both in the community and
      in the hypertensive population, with the clustering of cardiovascular risk
      factors observed in metabolic syndrome that promote progression of
      atherosclerosis. Renal function has to be routinely evaluated in every
      hypertensive patient, and the presence of minor alterations considered in the
      stratification of cardiovascular risk in hypertensive patients.

PMID- 15485418
TI  - Predictors of cardiovascular events in patients with type 2 diabetic nephropathy
      and hypertension: a case for albuminuria.
AB  - Individuals with type 2 diabetes and nephropathy represent a particularly high
      risk group for both adverse cardiac as well as renal events. Using the Irbesartan
      in Diabetic Nephropathy Trial (IDNT) cohort, our objective was to determine
      baseline characteristics of individuals with type 2 diabetic nephropathy and
      hypertension predictive for cardiac events. IDNT identified 1715 individuals with
      type 2 diabetic nephropathy and hypertension having serum creatinine of 1.0 to
      3.0 mg/dL and urinary albumin excretion rates > or = 900 mg/day. A cardiovascular
      (CV) composite was used consisting of CV death, nonfatal MI, hospitalization for
      heart failure, stroke, amputation, and coronary and peripheral revascularization.
      Using multivariable Cox regression analysis, 41 baseline characteristics
      determined a priori were analyzed for their potential relationship to risk of
      experiencing a CV event. Of the 1715 individuals, 518 (30.2%) had at least one of
      the CV composite end points. Older age, male gender, longer duration of diabetes,
      history of cardiovascular disease, history of CHF, high urinary
      albumin:creatinine ratio, and low serum albumin were strong predictors for CV
      events; of these, prior history of CVD (RR 2.00, 95% CI 1.63-2.45; P < 0.0001)
      and high urinary albumin:creatinine ratio (RR 1.29 per natural log unit, 95% CI
      1.13-1.48; P = 0.0002) at baseline were highly predictive for cardiovascular
      events. In conclusion, among individuals with hypertension and diabetic
      nephropathy, both the degree of albuminuria and lower serum albumin levels
      provide additional prognostic information concerning cardiovascular risk, in
      addition to traditional coronary risk factors.

PMID- 15485419
TI  - Albuminuria and cardiovascular risk in hypertensive patients with left
      ventricular hypertrophy: the LIFE Study.
AB  - Studies have shown that albuminuria is associated with increased risk for
      cardiovascular events. We tested the relationship between albuminuria (UACR) and
      cardiovascular risk in 8206 hypertensive patients with left ventricular
      hypertrophy included in the LIFE Study. Follow-up was 39,122 patient years. The
      risk for the primary composite cardiovascular end point increases continuously
      from the lowest to the highest decile of baseline UACR. No specific threshold
      could be identified. In conclusion, albuminuria predicts the outcome in the LIFE
      Study. The risk for cardiovascular morbidity and mortality among hypertensive
      patients with left ventricular hypertrophy increases at much lower UACR than has
      been reported in diabetic patients.

PMID- 15485420
TI  - Albuminuria as a predictor of cardiovascular and renal outcomes in people with
      known atherosclerotic cardiovascular disease.
AB  - BACKGROUND: Microalbuminuria predicts elevated cardiovascular risk in those with
      and without diabetes. In diabetes, microalbuminuria also heralds overt diabetic
      nephropathy. The predictive value of albuminuria below the microalbuminuria
      cutoff, and the development of overt nephropathy in nondiabetics with
      microalbuminuria, have not been well studied. We review findings of the HOPE
      Study. METHODS: The HOPE Study database includes data on first morning urine
      albumin/creatinine ratio (ACR) in 9043 participants at baseline, and in 7674
      participants at baseline and at last follow-up. Inclusion criteria were known
      vascular disease or diabetes, plus one other cardiovascular risk factor;
      exclusion criteria included heart failure or known impaired left ventricular
      function, dipstick-positive proteinuria (> 1+), and serum-creatinine > 2.3 mg/dL
      (200 micromol/L). Microalbuminuria was defined as an ACR > or = 2 mg/mmol.
      RESULTS: Microalbuminuria at baseline approximately doubled the relative risk
      (RR) of the primary outcome (myocardial infarction, stroke, or CV death). For
      every 1 mg/mmol rise of ACR, even below the level of microalbuminuria, the
      adjusted hazard of the primary outcome increased by about 15%. Baseline
      microalbuminuria predicted subsequent clinical proteinuria, RR 17.5, similarly in
      participants without and with diabetes. New microalbuminuria developed in 1542
      participants, and clinical proteinuria in 317. CONCLUSION: Albuminuria is a
      continuous risk factor for CV events even below the level of microalbuminuria.
      Microalbuminuria predicts clinical proteinuria in nondiabetics.

PMID- 15485421
TI  - Glomerular filtration of albumin: how small is the sieving coefficient?
AB  - A model was developed to describe how the concentration of albumin in proximal
      tubule fluid will vary with axial position, including the effects of luminal flow
      and water and albumin reabsorption. The results show that the high albumin
      sieving coefficients proposed recently cannot be reconciled with micropuncture
      data in rats.

PMID- 15485422
TI  - Albumin-like material in urine.
AB  - Recent studies have demonstrated the presence, in both rat and human urine, of a
      modified form of albumin not detected by conventional antibodies. This modified
      albumin behaves physicochemically as intact albumin under nondenaturing
      conditions. We have demonstrated this form of albumin to be disproportionately
      excreted in microalbuminuric states in diabetes. Quantitation of this modified
      form of albumin leads to the prediction of the onset of microalbuminuria in
      diabetic patients on average 3 to 4 years earlier than when measured by
      conventional immunoassays.

PMID- 15485423
TI  - Mechanism of albuminuria associated with cardiovascular disease and kidney
      disease.
AB  - The major underlying factors associated with tissue damage and fibrosis in
      cardiovascular and kidney disease are the up-regulation and action of growth
      factors such as transforming growth factor-beta (TGF-beta) and cytokines produced
      in response to changes in systemic factors, particularly blood pressure or
      hyperglycemia. This study identifies the relationship of elevated levels of TGF
      beta to increased levels of intact albumin in the urine (micro- and
      macroalbuminuria). This mechanism may be directly linked to the effect of TGF
      beta on albumin uptake and the lysosomal breakdown of filtered albumin by
      proximal tubular cells prior to excretion.

PMID- 15485424
TI  - Which method for quantifying urinary albumin excretion gives what outcome? A
      comparison of immunonephelometry with HPLC.
AB  - BACKGROUND: Microalbuminuria has recently been identified as an independent risk
      factor for cardiovascular disease in the general population. Immunochemical
      urinary albumin assays only detect immunoreactive intact albumin. High
      performance liquid chromatography (HPLC) is able to detect both immunoreactive
      and immunounreactive intact albumin. We compared both measurement methods
      respectively in subjects with normo-, micro-, and macroalbuminuria in the general
      population. METHODS: We used 24-hour urine samples that were collected within the
      framework of the second screening for the PREVEND Study, a prospective cohort
      study on albuminuria in the city of Groningen, The Netherlands. RESULTS: With
      nephelometry as immunochemical reference method, we classified 986 subjects as
      normoalbuminuric, 283 as microalbuminuric, and 43 subjects as macroalbuminuric.
      The mean +/- SD albumin concentration was 6.8 +/- 4.3 mg/L for nephelometry in
      the urine samples of the 998 subjects with a concentration <20 mg/L according to
      nephelometry versus 17.6 +/- 10.3 mg/L for HPLC (P < 0.001, HPLC 159% higher).
      These values were 58.9 +/- 40.6 mg/L for nephelometry versus 74.0 +/- 51.8 mg/L
      for HPLC (P < 0.001, N = 280, HPLC 26% higher) in the concentration range between
      20 to 200 mg/L, and 436.3 +/- 371.8 mg/L for nephelometry versus 399.1 +/- 329.2
      mg/L for HPLC above 200 mg/L (P = 0.048, N = 34, HPLC 8.5% lower). Associations
      of 24-hour urinary albumin excretion with cardiovascular risk factors were
      generally somewhat stronger for nephelometry than for HPLC. Logistic regression
      analyses with an abnormal ankle-brachial index as outcome parameter revealed
      adjusted odds ratios of 1.78 (95%CI 1.01-3.12, P < 0.05) and 4.67 (95%CI 1.68
      12.9, P < 0.05) respectively for micro- and macroalbuminuria as determined by
      HPLC, compared to 1.37 (95%CI 0.77-2.41, P = NS) and 3.85 (95%CI 1.53-9.67, P <
      0.05) respectively for nephelometry. The ROC-curve showed similar sensitivity and
      specificity for both methods (P = 0.25). CONCLUSION: The use of HPLC for
      determination of urinary albumin concentrations reveals higher values compared to
      nephelometry, especially in the lower concentration range, resulting in a higher
      prevalence of microalbuminuria. With HPLC compared to nephelometry, we found a
      21% higher independent odds ratio for microalbuminuria with the presence of
      peripheral vascular disease, and a 30% higher independent odds ratio for
      macroalbuminuria. This higher prevalence of microalbuminuria, accompanied with a
      similar absolute risk for peripheral vascular disease compared to patients with
      microalbuminuria detected by nephelometry, suggests HPLC to identify more people
      at risk, which is of great importance, especially when screening in large
      populations is concerned.

PMID- 15485425
TI  - Trends in the incidence of treated end-stage renal failure in The Netherlands:
      hope for the future?
AB  - This study shows that in The Netherlands there is a changing pattern in incidence
      of renal replacement therapy over time when adjusted for age and sex. There has
      been an almost linear increase in crude incidence rates during four decades.
      However, unlike the situation elsewhere in the Western world, a flattening of the
      curve has been observed during the last six years. The growing incidence of end
      stage renal disease (ESRD) due to especially hypertensive renovascular disease
      and diabetes mellitus type 2 has been neutralized by a decrease in ESRD due to
      glomerulonephritis, urologic interstitial nephritis, and diabetes mellitus type
      1. The latter observations suggest that renoprotective interventions can be
      successful on a population level, and thus, provide hope for the future. To
      battle the increase in ESRD due to atherosclerosis and diabetes mellitus type 2
      related renal disease, it is important that screening programs are being
      developed that enable us to identify in an early phase patients at risk for
      development of ESRD who may benefit from preventive strategies. Population
      screening for albuminuria will be helpful in this respect.

PMID- 15485426
TI  - Why is proteinuria an ominous biomarker of progressive kidney disease?
AB  - Progressive tubule injury and interstitial fibrosis frequently accompany
      glomerulopathies associated with proteinuria. Clinical experience indicates that
      higher levels of proteinuria prior to, as well as after initiation of treatment
      predict more rapid decline in renal function and more pronounced
      tubulointerstitial injury. It has been proposed that filtration of potentially
      tubulotoxic plasma proteins is responsible for the observed correlations between
      proteinuria and progression (i.e., proteinuria is a cause and not only a
      consequence of progressive renal injury). Numerous attempts have been made to
      identify the species of putative tubulotoxic proteins in this progressive injury
      process, but much uncertainty persists. These uncertainties stem from
      nonphysiologic exposure of apical cell surfaces to proteins in vitro, the
      extremely high concentrations of various proteins tested in vitro, and the
      nonuniformity of end points measured. Furthermore, there is often a lack of
      correlation between in vitro and in vivo findings, and a lack of uniformity of
      results even for seemingly similar in vitro experiments. Less controversy is
      evident in the potential pathways whereby injured tubules evoke a
      tubulointerstitial inflammatory and fibrotic response, with many in vivo models
      serving to incriminate excessive cytokine and chemokine production, infiltration
      of various inflammatory cells, and the balance between apoptosis and cell
      proliferation. Despite many years of concerted efforts, we believe it is still
      unclear whether proteinuria is a cause (and if so, which species of protein), or
      only a consequence of progressive renal injury. Nevertheless, pending the
      resolution of these uncertainties by more decisive and unambiguous
      experimentation, the strongly predictive inverse relationship between level of
      proteinuria and long-term renal survival currently justifies aggressive
      antiproteinuric treatment strategies, with a goal of reducing protein excretion
      rate to the lowest level possible without the induction of symptoms or undue
      risk.

PMID- 15485427
TI  - Proteinuria predicting outcome in renal disease: nondiabetic nephropathies
      (REIN).
AB  - About two thirds of patients on renal replacement therapy irreversibly lose their
      kidney function because of progressive nephropathies, such as diabetic
      nephropathy and nondiabetic chronic renal disease. Halting the progression of
      these patients to end-stage renal disease (ESRD) is instrumental to substantially
      decrease the need and cost for renal replacement therapy. A large number of
      experimental studies have demonstrated that chronic nephropathies share common
      pathogenic mechanisms that contribute to renal disease progression, even
      independently of the original etiology. Actually, a variety of insults may result
      in a common pathway of systemic hypertension, increased glomerular pressure and
      protein ultrafiltration, glomerular and tubular protein overload, chronic
      inflammation and, ultimately, scarring. Experimental and clinical data converge
      to indicate that in chronic renal disease increased protein traffic is
      nephrotoxic, proteinuria predicts disease progression, and proteinuria reduction
      is renoprotective. Initial clinical trials, mostly in patients with no or mild
      proteinuria, failed to demonstrate that ACE inhibition therapy is renoprotective
      in nondiabetic chronic nephropathies. Consistently, meta-analyses based on data
      generated by these trials failed to detect a specific, blood pressure
      independent, renoprotective effect of ACE inhibition therapy. The Ramipril
      Efficacy In Nephropathy (REIN) study found that ACE inhibitors, by reducing
      urinary proteins, may contribute to improve the outcome of nondiabetic renal
      disease, and reduce the risk of progression to ESRD by about 50%. Cumulative meta
      analyses, including the REIN study results, confirmed and extended these
      findings. Thus, well-designed trials in properly selected and carefully monitored
      study populations continue to be the best approach to test the efficacy of novel
      treatments. The meta-analyses may help confirming the consistency of these
      findings and their generalizability to larger cohorts of patients.

PMID- 15485428
TI  - Detecting and managing patients with type 2 diabetic kidney disease: proteinuria
      and cardiovascular disease.
AB  - BACKGROUND: The increasing prevalence of type 2 diabetes (T2DM) places more
      patients at risk for developing chronic kidney disease (CKD) or cardiovascular
      (CV) events. Effective therapy for CKD or CV disease (CVD) requires a method of
      identifying affected patients and monitoring the effectiveness of therapy.
      METHODS: We tested the predictive value of proteinuria for identifying patients
      at risk for progressive CDK and CVD, and monitoring treatment was determined
      using RENAAL study results. RESULTS: Baseline proteinuria identified patients at
      risk for progressive CKD and CVD. Suppression of proteinuria was associated with
      decreased likelihood of CKD or CVD. CONCLUSION: Proteinuria identifies the risk
      of CKD and CVD, and can be used to monitor the effectiveness of therapy.

PMID- 15485429
TI  - Impact of irbesartan, blood pressure control, and proteinuria on renal outcomes
      in the Irbesartan Diabetic Nephropathy Trial.
AB  - BACKGROUND: It is important to know the reliability of early changes in
      proteinuria in predicting late renal outcomes. The IDNT was a trial in which
      treatment assignment, baseline and follow-up blood pressure determinations, and
      albumin/creatinine ratios (ACR), and renal outcomes were recorded. METHODS: Risk
      of renal outcomes in the IDNT was assessed by proportional hazards modeling as a
      function of treatment assignment, and achieved systolic blood pressure (SBP) both
      without, and then with, inclusion of values for baseline proteinuria and early
      changes in proteinuria. RESULTS: In models without ACR variables, both treatment
      with irbesartan and achieved SBP during follow-up were significantly predictive
      of the risk of renal outcomes. Addition of ACR variables to the models reduced
      the apparent impact of assignment to irbesartan by 52% to 81%, and irbesartan was
      no longer a significant predictor of renal outcomes. Conversely, addition of ACR
      variables to the models attenuated the effect of achieved follow-up SBP by only
      32% to 46%, and follow-up BP remained a highly significant predictor of renal
      outcomes. CONCLUSION: The ability of early changes in proteinuria to predict the
      impact of treatment on renal outcomes is a function of the specific treatment.
      One must use caution in using early changes in proteinuria as a surrogate for
      longer-term renal outcomes.

PMID- 15485430
TI  - High-density mapping of left atrial endocardial activation during sinus rhythm
      and coronary sinus pacing in patients with paroxysmal atrial fibrillation.
AB  - INTRODUCTION: This study was designed to record global high-density maps of left
      atrial endocardial activation during sinus rhythm and coronary sinus pacing.
      METHOD AND RESULTS: Noncontact mapping of the left atrium was performed in nine
      patients with paroxysmal atrial fibrillation undergoing pulmonary vein ablation
      procedures. High-density isopotential and isochronal activation maps were
      superimposed on three-dimensional reconstructions of left atrial geometry.
      Mapping was repeated during pacing from sites within the coronary sinus. Earliest
      left atrial endocardial activation occurred anterior to the right pulmonary veins
      in seven patients and on the anterosuperior septum in two patients. A line of
      conduction block was seen in the posterior wall and inferior septum in all
      patients. The direction of activation in the left atrial myocardium overlying the
      coronary sinus was different from the electrogram sequence in the coronary sinus
      catheter in 6 of 9 patients. During coronary sinus pacing, activation entered the
      left atrium a mean (SD) of 41 (13) ms after the pacing stimulus at a site 12 (10)
      mm from the endocardium overlying the pacing electrode. Lines of conduction block
      were present in the posterior wall and inferior septum. CONCLUSION: In patients
      with paroxysmal atrial fibrillation, lines of conduction block are present in the
      left atrium during sinus rhythm and coronary sinus pacing. Electrograms recorded
      in the coronary sinus infrequently correspond to the direction of activation in
      the overlying left atrial myocardium.

PMID- 15485431
TI  - Prevention of atrial fibrillation: how important is transseptal atrial conduction
      in humans?

PMID- 15485432
TI  - Impact of coronary sinus lead position on biventricular pacing: mortality and
      echocardiographic evaluation during long-term follow-up.
AB  - INTRODUCTION: Biventricular pacing is an established treatment for congestive
      heart failure. Whether the anatomic location of the coronary sinus (CS) lead
      affects outcomes is unknown. The aim of this study was to evaluate the clinical
      response and mortality in patients who had transvenous CS leads placed in
      different anatomic branches for biventricular pacing. METHODS AND RESULTS: We
      evaluated 233 consecutive patients with New York Heart Association (NYHA) class
      III-IV heart failure and ejection fraction <35% who had successful placement of a
      transvenous left ventricular lead through a CS venous branch. Patients were
      divided into two groups based on anatomic lead position. Group 1 (n = 66)
      included leads in the anterior and anterolateral branches. Group 2 (n = 167)
      included leads in the lateral and posterolateral branches. Postimplant,
      functional capacity improved from an average 3.1 to 2.7 in group 1 (P = 0.001)
      and from 3.1 to 2.3 in group 2 (P = 0.001). Left ventricular ejection fraction
      (LVEF) measured by transthoracic echocardiography did not improve significantly
      in group 1 (pre-LVEF 18%, post-LVEF 20%; P = NS) but increased significantly from
      19% to 27% in group 2 (P = 0.008). Despite the difference in ejection fraction
      response, the mortality in the two groups after a mean follow-up of 546 days was
      similar (13.6% group 1 vs 17.9% group 2). CONCLUSION: Placement of the CS lead in
      the lateral and posterolateral branches is associated with significant
      improvement in functional capacity and greater improvement in left ventricular
      function compared with the anterior CS location. This improvement does not appear
      to influence mortality.

PMID- 15485433
TI  - Pattern of isthmus conduction recovery using open cooled and solid large-tip
      catheters for radiofrequency ablation of typical atrial flutter.
AB  - INTRODUCTION: Open cooled-tip and solid 8-mm-tip catheters have demonstrated
      safety and effectiveness for radiofrequency current (RFC) ablation of typical
      atrial flutter (AFL). However, data from prospective and randomized studies in
      this setting are lacking. METHODS AND RESULTS: One hundred thirty consecutive
      patients (104 men; 61 +/- 11 years) with AFL were randomized to undergo RFC
      catheter ablation either using a solid 8-mm-tip catheter (group A, 65 degrees C,
      70 W, 60 s) or an open irrigated-tip catheter (group B, 65 degrees C, 50 W, 60 s,
      17 mL/min flow). Endpoint was bidirectional conduction isthmus block. In cases of
      repeated (two times) transient isthmus block, the catheter was changed (crossed
      over) to the catheter used in the other randomization arm, but patients remained
      in the original group following intention-to-treat analysis. The selected
      endpoint could be achieved in all patients after 12 +/- 6 RFC pulses in group A
      and 10 +/- 7 RFC pulses in group B (P = 0.11). Procedure times were longer (159
      +/- 38 min vs 138 +/- 37 min, P = 0.002) and x-ray exposures higher in group A
      (fluoroscopy time 25 +/- 17 min vs 21 +/- 10 min, P = 0.08; x-ray dosage 3,133 +/
      2,576 cGy.cm2 vs 2,326 +/- 1,405 cGy.cm2, P = 0.03). Transient isthmus block was
      observed in 23 group A patients and 12 group B patients (P = 0.03). Onset time of
      transient isthmus block ranged from 0.5 to 27 minutes. Repeated transient isthmus
      block occurred in 8 of the 23 patients in group A after 19 +/- 3 RFC
      applications. After crossover to the cooled-tip catheter, the endpoint was
      reached another 5 +/- 1 RFC pulses. In group B, all patients could be treated
      without change of ablation catheter. After a follow-up of 14 +/- 2 months, 2
      patients (3%) in group A and 1 patient (1.5%) in group B presented with AFL
      recurrence. CONCLUSION: Open cooled-tip catheters are more effective than solid
      large-tip catheters for AFL ablation. The greater effectiveness is evident in
      cases showing repeated conduction recovery within the cavotricuspid isthmus.
      Primary use of open irrigated-tip catheters should be considered for AFL
      ablation.

PMID- 15485434
TI  - Catheter ablation of atrial flutter: do outcomes of catheter ablation with "large
      tip" versus "cooled-tip" catheters really differ?

PMID- 15485435
TI  - Magnetic resonance imaging findings in patients with Brugada syndrome.
AB  - INTRODUCTION: Cardiac magnetic resonance imaging (CMR) is a powerful diagnostic
      tool for evaluating cardiac structure and function. Recently, right ventricular
      wall-motion abnormalities were described using electron beam tomography in
      patients with Brugada syndrome. In the present study, we prospectively evaluated
      CMR findings in patients with Brugada syndrome compared to matched controls.
      METHODS AND RESULTS: CMR was performed on 20 consecutive patients with proven
      Brugada syndrome. The imaging protocol included breath-hold dark blood prepared
      T1-weighted multislice turbo spin-echo and gradient-echo images. Ventricular
      volumes and dimensions were compared to age- and sex-matched normal volunteers.
      The right ventricular outflow tract area was significantly enlarged in patients
      with Brugada syndrome compared to controls (11 vs 9 cm2, P = 0.018). There was a
      trend to larger right ventricular end-diastolic and end-systolic volumes and
      lower right ventricular ejection fraction in patients with Brugada syndrome
      compared to controls. However, none of the differences reached significance (P =
      0.3, P = 0.08, and P = 0.06, respectively). There was no statistically
      significant difference in the left ventricular parameters between patients and
      controls. High intramyocardial T1 signal similar to fat signal was observed in 4
      (20%) of the 20 patients compared to none of the controls. CONCLUSION: The
      findings support the view that subtle structural changes, such as right
      ventricular outflow tract dilation may point to a localized arrhythmogenic
      substrate in patients with Brugada syndrome.

PMID- 15485436
TI  - Magnetic resonance imaging findings in patients with Brugada syndrome.

PMID- 15485437
TI  - Effects of ablation, digitalis, and beta-blocker on dual atrioventricular nodal
      pathways and conduction during atrial fibrillation.
AB  - INTRODUCTION: Modification of AV nodal conduction by radiofrequency ablation
      (RFA) results in a variable reduction in heart rate during atrial fibrillation
      (AF). Using AF induced in patients with dual AV nodal pathways as a model, we
      tested the effect of additional treatment with digitalis (ouabain) and beta
      blocker (esmolol). METHODS AND RESULTS: Ten patients were randomized to control
      (group I) and studied only before ablation. AF was induced in 30 patients before
      and after slow pathway ablation (group II). Mean ventricular cycle lengths (AF
      CLmean) were recorded. Slow pathway conduction was eliminated after ablation in
      10 patients (group IIA), whereas slow pathway conduction was still present in 20
      patients (group IIB). Compared to pre-RFA there was a 10% increase in AF CLmean
      post-RFA (P < 0.01). During isoproterenol infusion the increase was 8% (P = NS).
      Adding digitalis and beta-blocker during isoproterenol infusion increased AF
      CLmean by 75% (95% in group IIA) compared to 36% in group I (P < 0.001 II vs I).
      CONCLUSION: Slow pathway ablation reduces ventricular rate during AF. Addition of
      digitalis and beta-blocker during isoproterenol infusion significantly decreases
      ventricular rate after ablation compared to the control group. The finding
      suggests that beta-blocker has significant effects on fast AV nodal pathway
      conduction during induced AF with isoproterenol infusion.

PMID- 15485438
TI  - Individual patterns of dynamic QT/RR relationship in survivors of acute
      myocardial infarction and their relationship to antiarrhythmic efficacy of
      amiodarone.
AB  - INTRODUCTION: Amiodarone is an effective antiarrhythmic drug, but it has serious
      side effects and conducted trials did not support its prophylactic use in
      survivors of acute myocardial infarction. It is possible that the prophylactic
      use of the drug has not been tested effectively. To optimize therapy outcome,
      markers of drug efficacy might be developed to identify patients who, although at
      arrhythmic risk, would not benefit from amiodarone treatment. We investigated
      descriptors of QT/RR relationship for their potential value in predicting
      inefficient amiodarone treatment. METHODS AND RESULTS: The study used 866 Holter
      recordings (462 amiodarone, 404 placebo) obtained 1 month after randomization in
      the European Myocardial Infarct Amiodarone Trial (EMIAT). A commercial Holter
      system was used to measure RR and QT intervals. Subject-specific descriptors of
      QT/RR relationship were calculated. Comparison was performed in amiodarone- and
      placebo-treated patients, distinguishing patients who did and did not suffer from
      arrhythmic death. QT/RR relationship and individually corrected QTc interval
      differed significantly, not only between amiodarone- and placebo-treated
      postmyocardial infarction patients but also between patients with and without
      arrhythmic death on amiodarone (QTc with vs without arrhythmic death 426.30 +/-
      33.93 ms vs 444.23 +/- 36.65 ms, P = 6.5 x 10(-3)). In a multivariate analysis,
      reduced optimum regression residuum (14.33 +/- 7.08 vs 20.11 +/- 9.39, P = 4.4 x
      10(-3)) and flatter slope (0.44 +/- 0.19 vs 0.55 +/- 0.24, P = 4.0 x 10(-2)) of
      the QT/RR relationship independently predicted arrhythmic death during follow-up.
      CONCLUSION: Chronic amiodarone treatment markedly affects the QT/RR relationship.
      The lack of treatment-related QT/RR changes predicts arrhythmic death.
      Descriptors of complexity of QT/RR relation seem to be potent markers of
      treatment efficiency.

PMID- 15485439
TI  - Can we predict antiarrhythmic efficacy or inefficacy of amiodarone or any other
      antiarrhythmic? What this patient needs is a doctor!

PMID- 15485440
TI  - Catheter ablation of common-type atrial flutter guided by three-dimensional right
      atrial geometry reconstruction and catheter tracking using cutaneous patches: a
      randomized prospective study.
AB  - INTRODUCTION: EnSite NavX (NavX) is a novel mapping and navigation system that
      allows visualization of conventional catheters for diagnostic and ablative
      purposes and uses them to create a three-dimensional (3D) geometry of the heart.
      NavX is particularly suitable for ablation procedures utilizing an anatomic
      approach, as in the setting of common-type atrial flutter (AFL). The aim of this
      study was to compare NavX-guided and conventional ablation procedures for AFL.
      METHODS AND RESULTS: Forty consecutive patients (32 male, 59 +/- 12 years) with
      documented AFL were randomized to undergo fluoroscopy-guided (group I, 20
      patients) or NavX-guided (group II, 20 patients) ablation, including 3D isthmus
      reconstruction. The same catheter setup was used in both groups. The endpoint of
      bidirectional isthmus block was obtained in all patients. Compared to
      conventional approaches, NavX-guided procedures significantly reduced fluoroscopy
      time (5.1 +/- 1.4 min vs 20 +/- 11 min, P < 0.01) and total x-ray exposure (5.1
      +/- 3.1 Gycm2 vs 24.9 +/- 1.6 Gycm2, P < 0.01). Isthmus geometry reconstruction
      could be performed in all patients of group II. In 4 patients (20%) of group II,
      anatomic isthmus variations were detected by NavX. No significant differences in
      radiofrequency current applications and procedural times were found between the
      two groups. CONCLUSION: NavX technology allows geometry reconstruction of the
      cavotricuspid isthmus. NavX-guided ablation of AFL reduces total x-ray exposure
      compared to the fluoroscopy-guided approach but does not prolong procedure time.

PMID- 15485441
TI  - Interaction of implantable defibrillator therapy with angiotensin-converting
      enzyme deletion/insertion polymorphism.
AB  - INTRODUCTION: The angiotensin-converting enzyme deletion allele (ACE D) decreases
      survival in patients with advanced heart failure. Whether the adverse impact on
      survival reflects an increased risk of pump failure or arrhythmic sudden death
      remains uncertain. If the ACE D genotype increases the risk of sudden death,
      implantable cardioverter defibrillator (ICD) therapy should diminish its negative
      impact. We sought to evaluate the effect of ICD therapy on ACE D genetic risk.
      METHODS AND RESULTS: The Genetic Risk Assessment of Cardiac Events (GRACE) study
      enrolled 479 patients at the University of Pittsburgh between 1996 and 2001.
      Blood was genotyped for the ACE D/I (deletion/insertion) polymorphism. Of the 479
      patients, 82 (77% male, 84% Caucasian, age 56 +/- 11 years, 60% ischemic, left
      ventricular ejection fraction 0.23 +/- 0.08) received an ICD and were selected
      for outcomes analysis (mean follow-up 871 +/- 538 days). Transplant-free survival
      and survival alone were compared in ACE DD patients (n = 24, 29%) versus ACE
      DI/II patients (n = 58, 71%). Survival was significantly improved in ACE DI/II
      patients compared to those without an ICD (1 year: 93% vs 87%; 2 year: 89% vs
      77%; P = 0.02) but not in ACE DD patients. Transplant-free survival among
      patients with an ICD was significantly worse in ACE DD versus ACE DI/II (1 year:
      67% vs 88%, 2 year: 55% vs 80%, P = 0.03). Analysis of survival as a single
      endpoint revealed a similar result (1 year = 78% vs 94%; 2 year: 72% vs 88%; P =
      0.05). ICD telemetry data showed a nonsignificant trend toward fewer individuals
      with arrhythmias in the ACE-DD group (46% vs 65%, P = 0.22) CONCLUSION: ICDs do
      not diminish the adverse influence of the ACE DD genotype on survival. This
      finding suggests that mortality in this high-risk genetic subset of patients is
      due to progression of heart failure rather than arrhythmic sudden death.

PMID- 15485442
TI  - Atrial ultrastructural changes during experimental atrial tachycardia depend on
      high ventricular rate.
AB  - INTRODUCTION: Atrial structural and electrophysiologic changes occur during
      atrial tachycardia. The role of high ventricular rate in these processes remains
      to be established. METHODS AND RESULTS: Six goats were subjected to 4 weeks of
      rapid atrioventricular (AV) pacing at an atrial and ventricular rate of 240
      beats/min, resulting in development of congestive heart failure. In another five
      goats, AV block was created. These goats then were subjected to 4 weeks of atrial
      pacing, also at 240 beats/min while the ventricular rate was kept low and regular
      at 80 beats/min (A-paced). Pacing was interrupted only for measurement of atrial
      effective refractory period and right atrial diameter. The ultrastructure of both
      atria was examined by light and electron microscopy, including quantification of
      the percentage of atrial extracellular matrix (%ECM). A group of six goats served
      as controls. In the AV-paced group, severe structural remodeling occurred in the
      atria, including severe loss of sarcomeres, glycogen accumulation, disruption of
      sarcoplasmic reticulum, and appearance of numerous small mitochondria and nuclei
      with homogeneously distributed chromatin. In contrast, structural changes were
      virtually absent in the atria of A-paced goats. Only a redistribution of nuclear
      chromatin and the appearance of numerous mitochondria were observed. The
      ultrastructure was normal in control animals. The%ECM was increased in AV-paced
      goats (29%) compared to A-paced animals (18%) and controls (17%) (P < 0.05).
      Finally, right atrial diameter increased by 51% in AV-paced goats but was
      unchanged in A-paced goats (P < 0.05). In both experimental groups, atrial
      effective refractory period shortened during pacing. CONCLUSION: Structural
      remodeling during chronic atrial tachycardia is related to the concomitant
      presence of a high ventricular rate and hence the occurrence of congestive heart
      failure rather than a high atrial rate. Electrical remodeling can occur in the
      absence of significant structural changes.

PMID- 15485443
TI  - Altered atrial structure begets atrial fibrillation, but how?

PMID- 15485444
TI  - Adaptive diastolic interval control of cardiac action potential duration
      alternans.
AB  - INTRODUCTION: Recent experimental and computational studies have shown that beat
      to-beat alternation in action potential duration can trigger cardiac reentry,
      suggesting that such "alternans" is a mechanistic precursor to arrhythmias. Given
      such a link, termination of alternans may help prevent the onset of arrhythmias.
      To this end, recent efforts have shown that chaos control methods can modulate
      the timing of electrical stimulation to eliminate alternans. METHODS AND RESULTS:
      We have developed an alternative control method founded entirely in cardiac
      electrophysiology (rather than borrowing techniques from the control of physical
      systems as with existing control techniques). Using computer simulations, we show
      that this method, which exploits the rate-dependent behavior of cardiac tissue,
      can be used to control alternans (and higher-order) rhythms, and is robust to
      drift and noise. When applied to individual model cells exhibiting alternans, the
      algorithm converges to the period-1 rhythm over as wide, and in some cases a
      wider, range of feedback proportionality constant values relative to existing
      methods. Control success comparable to existing methods is achieved when the
      algorithm is applied to a simulated one-dimensional Purkinje fiber exhibiting
      alternans. CONCLUSION: We have developed a method that adaptively controls the
      timing of electrical stimulation to rapidly eliminate action potential duration
      alternans in cardiac tissue. This control method may prove valuable in future
      arrhythmia prevention therapies.

PMID- 15485445
TI  - Nonlinear dynamic control of irregular cardiac rhythms.

PMID- 15485446
TI  - Adaptation of cardiac action potential durations to stimulation history with
      random diastolic intervals.
AB  - INTRODUCTION: The restitution hypothesis proposes that adaptation of cardiac
      action potential duration (APD) to rate changes is a predictor of ventricular
      fibrillation (VF). Conventional restitution kinetics plots the APD of a premature
      beat as a function of the previous diastolic interval (DI), and VF vulnerability
      is related to how rapidly APD shortens with decreasing DI. However, APD depends
      not only on the previous DI but also on the history of previous APDs and DIs. For
      a comprehensive understanding of APD restitution, we developed a random
      stimulation protocol and curve fitted each APD with the previous DIs and APDs
      using multiple autoregressive analyses. METHODS AND RESULTS: Guinea pig hearts (n
      = 5) were perfused and stained with di-4 ANEPPS to record optical APs from 252
      sites. Activation and repolarization times were detected in real time from one
      pixel and hearts were stimulated at random DIs (range 0-50 or 0-100 ms). We found
      that the first, second, and third previous APDs and DIs are required to obtain
      the best curve fit, which provides the most significant feedback control to APD
      and up to six previous beats contributed to curve fits (R > 0.8). The
      coefficients relating the previous DI to APD increased systematically in going
      from apex to base reflecting the intrinsic gradient of APD across the epicardium.
      CONCLUSION: Random restitution is more comprehensive than steady-state
      restitution, being based on random and dynamic DIs, and makes possible
      characterization of restitution in only 32 seconds to track changes in
      restitution during time-varying conditions such as ischemia/reperfusion.

PMID- 15485447
TI  - "Reconstituting" restitution?

PMID- 15485448
TI  - Mechanism for ST depression associated with contiguous subendocardial ischemia.
AB  - INTRODUCTION: A mechanism for ST depression arising on the epicardial surface
      over the border between normal and ischemic tissue is proposed. Depression is
      caused by current flowing in a transmural loop that begins and ends at the
      lateral boundary between healthy and ischemic tissue and passes through the
      transmural boundary between healthy and ischemic tissue. The result is ST
      depression at the epicardium over the lateral boundary. The size and direction of
      current flow are dictated by differences in the magnitude and orientation of
      anisotropic conductivity between those boundaries. METHODS AND RESULTS: Computer
      simulations verified and quantified the relationship between ST depression and
      conductivity differences. We used computer simulations based on an anatomically
      accurate, anisotropic model of canine ventricles and a bidomain representation of
      the effects of ischemia to verify the biophysical basis of this mechanism.
      CONCLUSION: ST depression at the epicardium appears over a lateral boundary
      between healthy and ischemic tissue.

PMID- 15485449
TI  - Immediate termination of fibrillation at 50% probability of overall success
      correlates with defibrillation dose-response curve width.
AB  - INTRODUCTION: Issues in transthoracic defibrillation, including waveform shape,
      fixed versus escalating dose protocol, and low- versus high-energy shocks, can be
      addressed by examining the defibrillation dose-response curve. We tested the
      hypothesis that, for commonly used defibrillation waveforms, the steepness of the
      overall defibrillation dose-response curve, measured as normalized curve width,
      correlates with the probability of a successful defibrillation being immediate at
      the shock intensity producing 50% success. METHODS AND RESULTS: We used 16
      isolated rabbit hearts to determine probability of overall success as a function
      of shock intensity and probability that a successful defibrillation is immediate
      rather than progressive (followed by several extrasystoles) at the shock
      intensity producing 50% overall defibrillation success. Two waveform pairs were
      tested--a monophasic damped sine versus a biphasic truncated exponential waveform
      commonly used for transthoracic defibrillation, and a monophasic/biphasic
      truncated exponential waveform pair similar to those used in internal
      cardioverter defibrillators. There was a close correlation between probability of
      a successful defibrillation being immediate at 150 and normalized curve width for
      the defibrillation dose-response curve. CONCLUSION: Our findings suggest that a
      high probability of successful defibrillation being immediate at low shock
      intensities is correlated with a narrow normalized curve width for the
      defibrillation dose-response curve.

PMID- 15485450
TI  - Dual conduction in a Mahaim fiber.
AB  - The case of an 8-year-old girl with incessant nonsustained left bundle branch
      block-like tachycardia refractory to antiarrhythmic drug therapy is reported.
      Electrophysiologic study revealed the presence of a right-sided accessory
      atriofascicular pathway. Episodes of nonsustained tachycardia were found to be
      based upon a dual response in AV conduction over the Mahaim fiber to one P wave.
      No reentrant tachycardia could be induced. The arrhythmia was cured by catheter
      ablation targeting a Mahaim potential at the right lateral tricuspid annulus. The
      findings can be explained by longitudinal dissociation in a single Mahaim fiber,
      a fiber distally diverging into two fibers with different conduction times, or
      (less likely) two closely located Mahaim fibers with different conduction times.

PMID- 15485451
TI  - Reentrant ventricular tachycardia originating from the aortic sinus cusp: a case
      report.
AB  - We report a case of idiopathic reentrant ventricular tachycardia (VT) originating
      from the left aortic sinus cusp. A prepotential preceding the QRS complex by 58
      ms was recorded from the posterior right ventricular (RV) outflow tract. During
      VT entrainment observed by pacing from the midseptal RV, it initially was
      orthodromically captured with a long conduction time but then antidromically
      captured as the pacing cycle rate was increased. Pacing at that site failed to
      show concealed entrainment despite a postpacing interval similar to the VT cycle
      length. Radiofrequency catheter ablation abolished the VT in the left aortic
      sinus cusp where a prepotential preceding the QRS complex by 78 ms with a
      postpacing interval similar to the VT cycle length was recorded in addition to
      concealed entrainment. The findings suggest that, in this VT, a critical slow
      conduction zone is partially present extending from the left aortic sinus cusp to
      the posterior right ventricular outflow tract. The patient has remained free from
      VT recurrence after 5-month follow-up.

PMID- 15485452
TI  - Two hearts and one defibrillator.
AB  - A patient who had undergone heterotopic heart transplantation and placement of an
      implantable cardioverter defibrillator in his native heart underwent generator
      change. Defibrillation testing induced ventricular fibrillation in his donor
      heart. To prevent this potentially lethal complication, defibrillator shock
      therapy must be synchronized to the donor heart R wave.

PMID- 15485453
TI  - Pulseless atrial fibrillation: a medical mystery?

PMID- 15485454
TI  - Prolongation of tachycardia cycle length during atrial flutter ablation: what is
      the underlying mechanism?

PMID- 15485455
TI  - The who, what, why, and how-to guide for circumferential pulmonary vein ablation.

PMID- 15485456
TI  - Anterior and posterior right middle pulmonary veins in a patient undergoing
      catheter ablation for atrial fibrillation.

PMID- 15485457
TI  - Insertion of an electrophysiologic catheter through a patent foramen ovale
      mimicking a coronary sinus position.

PMID- 15485458
TI  - Report on slide session, British Society for Haematology, 44th Annual Scientific
      Meeting, Cardiff, 2004.

PMID- 15485459
TI  - Bone marrow biopsy morbidity and mortality: 2002 data.
AB  - A survey of morbidity and mortality of bone marrow aspiration and trephine biopsy
      was carried out for the British Society of Haematology, covering the 12 months of
      2002. Fifty-three centres reported 13,506 procedures, comprising 3927 aspiration
      biopsies and 9579 combined procedures. There were 17 adverse events including
      nine instances of haemorrhage, four infections and one haemorrhage complicated by
      infection. Two trephine biopsy needles broke during the procedure. One patient
      suffered considerable pain for 2 weeks. The adverse event may have contributed to
      death in two patients and in a third patient was life-threatening. Risk factors
      for adverse events were identified.

PMID- 15485460
TI  - Determination of neutrophil Fcgamma receptor IIIb antigens (HNA-1a, HNA-1b and
      HNA-1c) by fluorescence-primed allele-specific polymerase chain reaction.
AB  - We evaluate a technique for genotyping HNA-1a, -1b and -1c antigens, resorting to
      fluorescence-primed allele-specific polymerase chain reaction (FPAS-PCR), and
      determine the frequency of the different genotypes in a normal Portuguese
      population. Our results indicate that the FPAS-PCR system is a reliable and
      simple tool for genotyping the neutrophil Fcgamma receptor IIIB antigens. The HNA
      1a, -1b and -1c gene frequencies of 42.98, 84.21 and 6.14%, respectively, found
      in this study are similar to those reported for other white populations.

PMID- 15485461
TI  - The relationship between serum cobalamin concentration and mean red cell volume
      at varying concentrations of serum folate.
AB  - There is concern that exposure of patients to folic acid may prevent the
      development of the macrocytosis of cobalamin deficiency and thus delay the
      detection of the neurological complications. We examined the relationship between
      low cobalamin levels and mean cell volume (MCV) at different serum folate
      concentrations in 63,472 blood samples tested in a community pathology laboratory
      over 2 years. We found no evidence that high serum folate levels masked the
      macrocytosis of cobalamin deficiency in this population with similar increases in
      MCV regardless of whether the serum folate was low, normal or high. Macrocytosis
      appears to retain its value as a marker of cobalamin deficiency in people with
      serum folate concentrations above the population average.

PMID- 15485462
TI  - Fluorouracil induces apoptosis and surface molecule modulation of peripheral
      blood leukocytes.
AB  - Little is known about the direct effect of chemotherapy on normal peripheral
      blood leukocytes (PBL) or its contribution to leukopenia. We examined 5'
      fluorouracil's (5FU) effect on PBL apoptosis and adhesion molecules' expression
      in a single-drug solid-tumor model. Possible apoptosis mediators were examined.
      The study included 32 colorectal cancer patients; apoptosis was determined by
      annexin-V binding and light-scatter morphology before and after drug infusion.
      CD18, CD11a, CD11b, and CD63 membranal levels were assayed by flow cytometry.
      Apoptosis was increased post-5FU administration in neutrophils (PMN), monocytes
      and lymphocytes (P < 0.05). Levels of Fas receptor and activated caspase 3 did
      not vary indicating that the process was not mediated by caspase 3 in the
      timeframe studied. Reduced CD63 on monocytes and decreased CD18 expression on PMN
      and non-apoptotic monocytes were observed (P < or = 0.05). CD11a,b expression did
      not vary. Decreased CD18 and CD63 levels were demonstrated in apoptotic and non
      apoptotic PBL implying a more direct association with the drug itself.

PMID- 15485463
TI  - Anagrelide treatment in 52 patients with chronic myeloproliferative diseases.
AB  - In this retrospective multi-centre study, we report our experience with
      anagrelide in the treatment of thrombocytosis in patients with chronic
      myeloproliferative diseases. Our study included 52 patients (age 20-78 years).
      The initial anagrelide dose was, in general, 0.5 mg once daily and mean
      maintenance dosage was 1.7 mg/day. The overall response rate was 79% including
      75% complete remission and 4% partial remission. Forty-two patients (81%) had
      adverse effects and in 29% of the study population, the adverse effects
      necessitated cessation of anagrelide. The most common adverse effect was moderate
      anaemia (50%). Two patients experienced erectile dysfunction which has been
      described only once previously in association with anagrelide treatment. One
      patient progressed to acute leukaemia. However, this patient had been pre-treated
      with two potentially leukaemogenic drugs and had only been in short-term
      treatment with anagrelide. Furthermore, a total of 13 events were recorded. More
      than 25% of these events occurred in patients with platelet counts between 400
      and 600 x 10(9)/l and almost 40% of all events occurred in patients with platelet
      counts above 400 x 10(9)/l. This observation supports the hypothesis that
      aggressive control of thrombocytosis to a platelet count <400 x 10(9)/l might
      reduce the number of thrombohaemorrhagic events. Anagrelide is safe and effective
      in reducing the platelet counts, but a high proportion of the patients
      discontinue treatment because of the adverse effects of the drug.

PMID- 15485464
TI  - Evaluation of primary haemostasis in people with neurofibromatosis type 1.
AB  - Assessment of haemostasis in people with neurofibromatosis type 1 (NF-1) is
      essentially lacking, despite case reports of an association with von Willebrand
      disorder (VWD) and reported excessive bleeding post-surgery. We assessed routine
      blood haematology, routine coagulation parameters [prothrombin time (PT),
      activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen],
      coagulation factors II, V, VII, VIII, IX, X, XI and XII, von Willebrand (VWF)
      factor antigen and activity, and platelet function [using the platelet function
      analyser (PFA-100)] in a group of individuals with NF-1 (n = 30). Their perceived
      haemorrhagic bleeding risk was also graded by means of a structured clinical
      assessment and physical examination. Routine blood assessments including platelet
      counts were generally normal, as were the routine coagulation tests PT, TT and
      fibrinogen, and most coagulation factors. Elevated APTTs were detected in 11
      individuals, reduced factor XII levels in three, reduced VWF levels in four, and
      elevated PFA closure times (CTs) in 13. Laboratory results correlated with each
      other in some but not all cases. For example, elevated APTTs were identified in
      two of three individuals with a reduced factor XII level and prolonged CTs were
      identified in three individuals who also showed reduced aggregation responses in
      classical platelet function studies. Moreover, all individuals with VWF results
      below the normal reference range showed elevated CTs with both PFA test
      cartridges, and those with VWF results identified as borderline normal (i.e. 50
      65%) also showed elevated CTs with both PFA test cartridges in three of five
      cases. The relationship between VWF and CTs was also identified by linear
      regression analysis (P-values of <0.05, for all comparisons). However, as
      clinically perceived bleeding risk did not appear to be correlated with
      laboratory test results in most cases, blanket screening of NF-1 individuals for
      evaluation of laboratory haemostasis may not be warranted.

PMID- 15485465
TI  - Platelet larger cell ratio (P-LCR) in patients with dyslipidemia.
AB  - We have described preliminary results of platelet larger cell ratio (P-LCR)
      analysis, provided by an automated hematology analyzer in patients with
      hypercholesterolemia and/or hypertriglyceremia. P-LCR values were significantly
      higher in patients (n = 41) than in control normal group (n = 20) (P < 0.0001).
      Larger platelets are more reactive and contribute to vasooclusive events in
      patients with dyslipidemia. P-LCR may be used as an indicator of risk factor for
      thromboembolic ischemic events.

PMID- 15485466
TI  - Subacute immune response to primary EBV infection leading to post-transplant
      lymphoproliferative disease in a renal transplant patient.
AB  - A 23-year-old man sero-negative for Epstein-Barr virus (EBV) developed recurrent
      sore throats 3 and 6 months after a renal transplant from an EBV sero-positive
      donor. Tonsillar biopsy at 9 months post-transplant showed post-transplant
      lymphoproliferative disease (PTLD) caused by EBV. Following reduction of
      immunosuppressive treatment, he developed further signs and symptoms, and
      serological evidence of infectious mononucleosis followed by resolution of
      lymphadenopathy. This case emphasizes the difficulty in interpreting EBV serology
      in immunosuppressed patients and the importance of pre-transplant EBV serology.

PMID- 15485467
TI  - Laboratory diagnosis of a compound heterozygosity for Hb Hekinan [alpha27(B8) Glu
      Asp] and a deletional alpha-thalassaemia 2 in Thailand.
AB  - We report the haematological and molecular characterization of a previously
      undescribed condition of compound heterozygosity for haemoglobin (Hb) Hekinan
      [alpha27(B8) Glu-Asp] and a deletional alpha-thalassaemia 2 detected in a Thai
      individual. Hb analysis demonstrated that although this Hb variant co-migrates
      with Hb A on cellulose acetate electrophoresis and cation-exchange high
      performance liquid chromatography (HPLC), the HPLC procedure using a weak cation
      exchange material with polyaspartic acid could clearly differentiate the two Hb.
      The variant could then be confirmed using the polymerase chain reaction
      restriction fragment-length polymorphism (PCR-RFLP) analysis of the amplified
      alpha1-globin gene.

PMID- 15485468
TI  - Transient atypical monocytosis mimic acute myelomonocytic leukemia in post
      chemotherapy patients receiving G-CSF: report of two cases.
AB  - Granulocyte colony-stimulating factor (G-CSF) is now widely used in patients with
      malignant disorders receiving intensive chemotherapy to increase leukocyte count
      and to upregulate phagocyte function during neutropenia. Monocytosis associated
      with G-CSF has been reported in anecdotal literature. We report two cases of
      pseudoleukemia secondary to G-CSF administration. Both patients initially
      presented with myelodysplastic syndrome with chromosome 7 abnormalities that
      evolved into acute myeloid leukemia. Case one had deletion 7q while case two
      initially had monosomy 7 and subsequently developed a balanced translocation
      between the short (p) arm of chromosome 1 and long (q) arm of chromosome 15.
      Following the induction chemotherapy and G-CSF administration, both of these
      patients developed pseudoleukemia. Patient 1 had white blood cell (WBC) count of
      26 x 10(9)/l with 72% monocytes, while patient two had WBC of 14.1 x 10(9)/l with
      30% monocytes. In both patients the monocytosis resolved after the
      discontinuation of G-CSF therapy. In summary, patients treated with G-CSF should
      be followed closely. In those cases with pseudoleukemia discontinuation of the
      drug with no supplemental chemotherapy is probably enough to control the atypical
      monocytosis.

PMID- 15485469
TI  - Effect of lansoprazole for an idiopathic thrombocytopenic purpura patient with
      Helicobacter pylori infection who did not respond to prednisolone treatment.

PMID- 15485470
TI  - Sedation with intravenous midazolam and intravenous opiate is superior to
      intravenous midazolam alone for bone marrow biopsy procedures.

PMID- 15485471
TI  - Hormone replacement therapy and cardiovascular disease: increased risks of venous
      thromboembolism and stroke, and no protection from coronary heart disease.
AB  - Hormone replacement therapy (HRT) was increasingly promoted over the last 40
      years to improve quality of life, and to reduce the risks of osteoporotic
      fractures and coronary heart disease (CHD). In recent years, observational
      studies, randomized trials and systematic reviews of such trials have shown that
      HRT does not reduce, but actually increases cardiovascular risk. HRT increases
      the relative risks of venous thromboembolism (twofold), and of fatal or disabling
      stroke (by 50%); whilst increasing the early risk of myocardial infarction and
      having no protective effect against CHD on longer term use. Possible mechanisms
      for these increased cardiovascular risks include down-regulation of several
      inhibitory pathways of blood coagulation, resulting in increased coagulation
      activation, which promotes venous and arterial thrombosis. The implications for
      prescription are discussed, as are lessons for future evaluation of health care
      interventions.

PMID- 15485472
TI  - Beyond bone mineral density: can existing clinical risk assessment instruments
      identify women at increased risk of osteoporosis?
AB  - OBJECTIVE: Although osteoporosis and fragility fracture are common amongst
      postmenopausal women, the extent of risk varies, and measurement of bone mineral
      density (BMD) is the standard tool used to diagnose and assess fracture risk.
      Rates of diagnosis remain relatively low, and several groups have developed
      instruments to help identify individuals who would most benefit from BMD testing.
      In this paper, we review and compare the performance of these instruments to
      identify those most useful in the primary care setting. DESIGN: Review of
      screening instruments comprised osteoporosis clinical risk factors and comparison
      of the sensitivity and specificity of these algorithms. RESULTS: Validated
      instruments have varying complexity, but similar sensitivity and specificity for
      identifying individuals who are likely to have low BMD. The area under the
      receiver operating characteristic curve ranges from 0.75 (SOFSURF) to 0.81
      (SCORE). The simplest of the instruments (OST) uses only age and weight and has
      an AUC of 0.79. CONCLUSIONS: The Osteoporosis Self-assessment Tool, the simplest
      of the instruments, performs as well as more complex tools and, because of its
      simplicity, may be the most useful means for the busy clinician to identify
      postmenopausal women who would most benefit from BMD testing.

PMID- 15485473
TI  - Diagnosing heart failure in aortic valve stenosis.
AB  - OBJECTIVE: In aortic valve stenosis (AS), heart failure (HF) omens a high risk of
      death and is an indication for prompt valve replacement. We studied whether its
      detection can be facilitated by measuring plasma N-terminal B-type natriuretic
      peptide (Nt-BNP) or by estimating pulmonary capillary wedge pressure (PCWP) using
      echocardiography. DESIGN AND SETTING: A cross-sectional cohort study in a
      university hospital. SUBJECTS AND METHODS: We studied 137 consecutive adult
      patients referred to our unit for invasive evaluation of isolated AS. All
      patients underwent cardiac catheterization, measurement of plasma Nt-BNP and
      estimation of PCWP by Doppler echocardiography of transmitral and pulmonary
      venous flow velocities. The final diagnosis of HF was based on the combined
      criteria of dyspnoea on ordinary effort and PCWP >14 mmHg at cardiac
      catheterization. The performance of Nt-BNP and the PCWP estimate in the detection
      of HF were studied using receiver operating characteristic (ROC) analysis.
      RESULTS: Totally 42 patients had HF. A cardiologist's clinical diagnosis of HF
      had high specificity (94%) but poor sensitivity (66%). With an optimized cut-off
      point, plasma Nt-BNP had moderate sensitivity (77%) and specificity (79%) for HF;
      the ROC area was 0.83. The echocardiographic PCWP estimate classified 90% of
      patients correctly as having normal or truly elevated (>14 mmHg) PCWP. Its
      sensitivity and specificity for the diagnosis of HF were 80 and 95% respectively;
      the ROC area was 0.88. With a cut-off point of 12 mmHg, the sensitivity of the
      PCWP estimate was 85% and specificity, 88%. CONCLUSION: The recognition of HF in
      patients with AS can be improved by estimating PCWP using Doppler
      echocardiography of transmitral and pulmonary venous flow velocities.

PMID- 15485474
TI  - A randomized trial comparing phosphorylcholine-coated stenting with balloon
      angioplasty as well as abciximab with placebo for restenosis reduction in small
      coronary arteries.
AB  - OBJECTIVE: The objective of this randomized trial was to assess the
      antirestenotic effects of phosphorylcholine (PC)-coated stents as well as of
      abciximab in small coronary arteries when compared with percutaneous transluminal
      coronary angioplasty (PTCA) and placebo respectively. BACKGROUND: Stent coating
      with PC has been shown to reduce protein absorption and platelet activation which
      may reduce the risk of restenosis. Furthermore, on the basis of nondedicated
      studies abciximab is believed to reduce the risk of restenosis after coronary
      interventions. METHODS: A total of 502 patients with lesions situated in small
      coronary arteries (vessel diameter </=2.5 mm) were randomly assigned to be
      treated with either PC-coated stents (n = 253) or PTCA (n = 249) and with either
      abciximab (n = 251) or placebo (n = 251) with the use of a 2 x 2 factorial
      design. All patients were pretreated with 600 mg clopidogrel. The primary end
      point was the incidence of angiographic restenosis (>/=50% diameter stenosis) at
      follow-up; death or myocardial infarction, and target vessel revascularization
      (TVR), were assessed as secondary end-points. RESULTS: Angiographic restenosis
      did not differ between patients treated with PC-coated stents or with PTCA (39.0%
      vs. 34.2%; P = 0.30) and between patients receiving abciximab or placebo (39.3%
      vs. 34.3%; P = 0.29). Similarly, the need for TVR at 1-year follow-up did not
      differ between patients receiving PC-coated stents or PTCA (20.2% vs. 20.5%; P =
      0.98) as well as between patients treated with abciximab or placebo (18.7% vs.
      21.9%; P = 0.44). CONCLUSIONS: PC-coated stents and abciximab failed to reduce
      the incidence of angiographic restenosis after percutaneous coronary intervention
      of small coronary arteries. These data strengthen the belief that future studies
      on prevention of restenosis in small coronary arteries should focus on drug
      eluting stents.

PMID- 15485475
TI  - Impairment of coronary circulation by acute hyperhomocysteinaemia and reversal by
      antioxidant vitamins.
AB  - OBJECTIVE: To evaluate the effect of acute hyperhomocysteinaemia with and without
      antioxidant vitamins pretreatment on coronary circulation and circulating
      chemokine levels. DESIGN: Observer-blinded, randomized crossover study. SETTING:
      This study was conducted at a university hospital and at a general hospital in
      Italy. SUBJECTS: Sixteen healthy hospital staff volunteers (nine men, seven
      women), aged 26-40 years. INTERVENTIONS: Subjects were given each three loads in
      random order at 1-week intervals: oral methionine, 100 mg kg(-1) in fruit juice;
      the same methionine load immediately following ingestion of antioxidant vitamin
      E, 800 IU, and ascorbic acid, 1000 mg; and methionine-free fruit juice (placebo).
      MAIN OUTCOME MEASURES: Coronary flow velocity reserve (CFVR), assessed by
      noninvasive transthoracic Doppler echocardiography, blood pressure, heart rate,
      lipid and glucose, monocyte chemoattractant protein-1 (MCP-1) and interleukin-8
      (IL-8) parameters evaluated at baseline and 4 h following ingestion of the loads.
      RESULTS: The oral methionine load increased plasma homocysteine from 12.8 +/- 1.8
      to 33.3 +/- 3.4 micromol L(-1) at 4 h (P < 0.001). A similar increase was
      observed with same load plus vitamins (P < 0.001) but not with placebo (P =
      0.14). Circulating MCP-1 and IL-8 levels rose after the methionine load (P <
      0.001), but not after placebo or methionine plus vitamins. The methionine load
      significantly reduced CFVR (decrease, 26 +/- 8.2%; P < 0.001). The methionine
      load with ingestion of vitamins partially prevented the impairment of CFVR
      (decrease, 11 +/- 4%; P < 0.001). CONCLUSION: Our data suggest that acute
      hyperhomocysteinaemia reduces CFVR and increases plasma MCP-1 and IL-8 levels in
      healthy subjects. Pretreatment with antioxidant vitamin E and ascorbic acid
      prevents the effects of hyperhomocysteinaemia, suggesting an oxidative mechanism.

PMID- 15485476
TI  - Autosomal recessive hypercholesterolaemia: normalization of plasma LDL
      cholesterol by ezetimibe in combination with statin treatment.
AB  - BACKGROUND: Severe hereditary hypercholesterolaemia is most frequently due to
      familial hypercholesterolaemia (FH), caused by mutations in the LDL receptor
      (LDLR) gene. However, a phenotype very similar to FH may also be caused by
      defects in other genes like the genes for apolipoprotein (apo) B-100 or autosomal
      recessive hypercholesterolaemia (ARH). SUBJECT: An 8-year-old male of Lebanese
      origin was diagnosed with severe hypercholesterolaemia and extensive cutaneous
      and tendon xanthomas. Plasma LDL cholesterol before treatment was 17 mmol L(-1),
      whilst parents and both siblings had normal levels. DIAGNOSIS: Degradation of
      (125)I-labelled LDL in blood lymphocytes was reduced, but not abolished.
      Sequencing analysis of the LDLR and apoB-100 genes were negative, whilst a splice
      acceptor mutation in intron 1 (IVS 1 -1G>C) was detected in the ARH gene. The
      patient was homozygous for the mutation, whilst the parents were heterozygous.
      These findings were in agreement with a diagnosis of ARH. TREATMENT AND CLINICAL
      COURSE: Monthly LDL apheresis and atorvastatin 120 mg daily reduced LDL
      cholesterol preapheresis level to 4.8 mmol L(-1). When ezetimibe was given 10 mg
      day(-1) in combination with rosuvastatin 80 mg day(-1), LDL cholesterol was
      further lowered to 1.6 mmol L(-1), which made apheresis unnecessary. Cutaneous
      and tendon xanthomas disappeared completely and the intima-media thickness of the
      common carotid arteries decreased. At age 23 he developed a small myocardial
      infarction. CONCLUSION: ARH should be considered in cases of severe
      hypercholesterolaemia with a pattern of recessive inheritance. Combination
      therapy with high-dose statin and ezetimibe seems to be the treatment of choice
      in ARH and may reduce or eliminate the need for LDL apheresis treatment.

PMID- 15485477
TI  - Oxidized low-density lipoprotein in plasma is a prognostic marker of subclinical
      atherosclerosis development in clinically healthy men.
AB  - OBJECTIVE: To investigate the association between plasma oxidized low-density
      lipoprotein (OxLDL) and the progress of clinically silent atherosclerosis, as
      measured by ultrasound in the carotid arteries. DESIGN: Prospective,
      observational study with more than 3 years of follow-up. SETTING: One-centre
      study at university hospital. MATERIAL AND METHODS: The subjects (n = 326) were
      obtained by stratified sampling from a population sample of men who were 58 years
      old at baseline. Carotid artery intima-media thickness (IMT) was measured
      bilaterally by high-resolution B-mode ultrasound at baseline and after follow-up.
      Plasma OxLDL cholesterol concentrations and conventional cardiovascular risk
      factors were measured at study entry. Automated measurements of IMT were
      performed. Plaque occurrence and size were assessed (plaque status). Plasma OxLDL
      at entry was measured by a specific monoclonal antibody, mAb-4E6. RESULTS: OxLDL
      at entry, but not LDL cholesterol, was associated with the number and size of
      plaques at follow-up (P = 0.008), also after adjustment for plaque status at
      entry (P = 0.033). The plasma OxLDL concentration at entry was associated with
      change in carotid artery IMT (r = 0.17; P = 0.002) and in a stepwise multiple
      regression analysis this association remained after adjustment for other
      cardiovascular risk factors (P = 0.005). CONCLUSIONS: These results provide new
      information, supporting the concept that circulating OxLDL was associated with
      the silent phase of atherosclerosis progression in clinically healthy men
      independently of conventional risk factors.

PMID- 15485478
TI  - Inflammatory markers and heart rate variability in women with coronary heart
      disease.
AB  - PURPOSE: Both heart rate variability (HRV) and inflammatory markers are carrying
      prognostic information in coronary heart disease (CHD), however, we know of no
      studies examining their relation in CHD. The aim of this study, therefore, was to
      assess the association between HRV and inflammatory activity, as reflected by the
      levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1ra) and C-reactive
      protein (CRP). SUBJECTS AND METHODS: Consecutive women patients who survived
      hospitalization for acute myocardial infarction, and/or underwent a percutaneous
      transluminal coronary angioplasty or a coronary artery bypass grafting were
      included and evaluated in a stable condition 1 year after the index events. An
      ambulatory 24-h ECG was recorded during normal activities. SDNN index (mean of
      the standard deviations of all normal to normal intervals for all 5-min segments
      of the entire recording) and the following frequency domain parameters were
      assessed: total power, high frequency (HF) power, low frequency (LF) power and
      very low frequency (VLF) power. Levels of high-sensitivity CRP were measured by
      nephelometry, IL-6 and IL-1ra concentrations were determined by enzyme
      immunoassay. RESULTS: Levels of IL-6 showed an inverse relation with HRV measures
      even after controlling for potential confounding factors. The P-values were 0.02,
      0.04, 0.01, 0.03, 0.18 for the multivariate association with SDDN index, total
      power, VLF power, LF power and HF power respectively. In contrast, the inverse
      relationship between HRV measures and CRP or IL-1ra levels were weak and
      nonsignificant. Correlation coefficients for the relationship between IL-6 and
      HRV measures were both uni- and multivariately higher than for the relationship
      between HRV measures and any other factors evaluated in this study. CONCLUSION:
      Concentration of IL-6 showed a negative, independent association with HRV in
      women with CHD. Thus, increased inflammatory activity, as reflected by IL-6
      levels, may represent a new auxiliary mechanism linking decreased HRV to poor
      prognosis in CHD.

PMID- 15485479
TI  - Prevalence of macrovascular disease amongst type 2 diabetic patients detected by
      targeted screening and patients newly diagnosed in general practice: the Hoorn
      Screening Study.
AB  - OBJECTIVES: Screening for type 2 diabetes has been recommended and targeted
      screening might be an efficient way to screen. The aim was to investigate whether
      diabetic patients identified by a targeted screening procedure differ from newly
      diagnosed diabetic patients in general practice with regard to the prevalence of
      macrovascular complications. DESIGN: Cross-sectional population-based study.
      SETTING: Population study, primary care. SUBJECTS: Diabetic patients identified
      by a population-based targeted screening procedure (SDM patients), consisting of
      a screening questionnaire and a fasting capillary glucose measurement followed by
      diagnostic testing, were compared with newly diagnosed diabetic patients in
      general practice (GPDM patients). Ischaemic heart disease and prior myocardial
      infarction were assessed by ECG recording. Peripheral arterial disease was
      assessed by the ankle-arm index. Intima-media thickness of the right common
      carotid artery was measured with ultrasound. RESULTS: A total of 195 SDM patients
      and 60 GPDM patients participated in the medical examination. The prevalence of
      MI was 13.3% (95% CI 9.3-18.8%) and 3.4% (1.0-11.7%) in SDM patients and GPDM
      patients respectively. The prevalence of ischaemic heart disease was 39.5% (95%
      CI 32.9-46.5%) in SDM patients and 24.1% (15.0-36.5%) in GPDM patients. The
      prevalence of peripheral arterial disease was similar in both groups: 10.6% (95%
      CI 6.9-15.9%) and 10.2% (4.7-20.5%) respectively. Mean intima-media thickness was
      0.85 mm (+/-0.17) in SDM patients and 0.90 mm (+/-0.20) in GPDM patients. The
      difference in intima-media thickness was not statistically significant.
      CONCLUSIONS: Targeted screening identified patients with a prevalence of
      macrovascular complications similar to that of patients detected in general
      practice, but with a lower degree of hyperglycaemia.

PMID- 15485480
TI  - Hormone therapy and mortality during a 14-year follow-up of 14 324 Norwegian
      women.
AB  - OBJECTIVES: We evaluated mortality from cardiovascular disease (CVD), coronary
      heart disease (CHD) and all causes in relation to use of any hormone therapy (HT)
      and HT with oestradiol and norethisterone or levonorgestrel. DESIGN: Population
      based cohort study. SETTING AND SUBJECTS: Women in three Norwegian counties were
      invited to a health survey in 1985-88 and 82.8% participated. In all 14 324 post-
      or perimenopausal women aged 35-62 years, including 702 HT users with a mean age
      of 48.8 years, were followed for 14 years. RESULTS: Women using HT had mortality
      from all causes and CVD comparable with that of nonusers. The relative risk (RRs)
      for CVD mortality amongst all women were 0.69 (95% CI: 0.35-1.33) for users of
      HT, and 0.96 (95% CI: 0.43-2.17) for users of HT with norethisterone or
      levonorgestrel. Amongst women free of self-reported cardiovascular health
      problems at baseline all-cause, CVD and CHD mortality tended to be lower amongst
      users of HT whilst HT use was linked with increased mortality amongst women with
      cardiovascular health problems. CONCLUSIONS: In this cohort of women around the
      usual age of menopause all-cause or CVD mortality amongst users of HT, most often
      oestradiol combined with norethisterone or levonorgestrel, was not markedly
      different from that of nonusers. Early CHD events amongst HT users prior to the
      baseline survey, together with selective inclusion of healthy subjects, may in
      part explain protective effects of HT on CHD reported from previous observational
      studies.

PMID- 15485481
TI  - A population-based intervention study on elevated serum levels of methylmalonic
      acid and total homocysteine in elderly people: results after 36 months of follow
      up.
AB  - OBJECTIVES: To study the effects of vitamin B12 and folic acid treatment on
      haematological measures, reported symptoms and clinical findings over a 3-year
      period. DESIGN: A longitudinal two-cohort study. SETTING: A mid-Swedish
      community. SUBJECTS: A 20% random sample of persons 70 years or older in a
      defined geographical area were invited to a survey (n = 266). Sixty-nine persons
      who had serum cobalamin <300 pmol L(-1) and serum methylmalonic acid (MMA)
      >/=0.37 micromol L(-1) or serum total homocysteine (tHcy) >/=15 micromol L(-1)
      and who had no vitamin B12 or folic acid substitution were selected for
      treatment. MAIN OUTCOME MEASURES: Serum cobalamin, folate, MMA and tHcy. Presence
      of gastrointestinal, neurological, psychiatric and some other symptoms, obtained
      by questionnaire, and Mini Mental State Examination (MMSE) score, vibration sense
      measurement and findings at a physical examination. RESULTS: After combined
      vitamin B12-folic acid treatment, all persons normalized their serum tHcy and MMA
      levels and the effect remained after 3 years. The study design allowed separation
      of pure vitamin B12 deficiencies from folate and combined deficiencies. There was
      a tendency towards improvement of vibration sense, especially in the long nerve
      paths, and improvement of neurological symptoms and oral mucosa findings. No
      improvement was seen for other symptoms, reflex activity or MMSE score.
      CONCLUSIONS: Vitamin treatment of elderly people in the early phase of the
      condition may reverse damage that otherwise would become irreversible. If
      initiated, the treatment should be combined with vitamin B12 and folic acid.

PMID- 15485482
TI  - Discordant penetrance of the trait for familial amyloidotic polyneuropathy in two
      pairs of monozygotic twins.
AB  - BACKGROUND: Familial amyloidotic polyneuropathy (FAP) is caused by mutated
      transthyretin in which valine at position 30 is substituted by methionine (ATTR
      Val30Met). FAP is inherited as an autosomal dominant trait with variable
      penetrance. CASES: Two pairs of DNA confirmed monozygotic twin brothers, 63 and
      37 years of age respectively, who are heterozygous for the ATTR Val30Met gene,
      have been identified in Sweden. In the first twin pair (A), the onset of typical
      FAP symptoms occurred at the age of 48 for twin A1, whilst his twin brother (A2)
      is still free from FAP symptoms 13 years later. In the second pair of twins (B),
      the onset of polyneuropathy occurred at the age of 34 for the proband (B1),
      whilst his brother (B2) is healthy 3 years after the onset of his brother's
      disease. DISCUSSION: In the following, a detailed description of the clinical
      presentation of the Swedish twin pairs is provided together with a discussion of
      possible environmental factors initiating the onset of the disease.

PMID- 15485483
TI  - A modified beta-amyloid hypothesis: intraneuronal accumulation of the beta
      amyloid peptide--the first step of a fatal cascade.
AB  - Accumulating evidence points to an important role of intraneuronal A beta as a
      trigger of the pathological cascade of events leading to neurodegeneration and
      eventually to Alzheimer's disease (AD) with its typical clinical symptoms, like
      memory impairment and change in personality. In the present article, we review
      recent findings on intracellular monomeric and oligomeric beta-amyloid (A beta)
      generation and its pathological function in cell culture, transgenic AD mouse
      models and post mortem brain tissue of AD and Down syndrome patients, as well as
      its interaction with oxidative stress and its relevance in apoptotic cell death.
      Based on these results, a modified A beta hypothesis is formulated, that
      integrates biochemical, neuropathological and genetic observations with AD
      typical neuron loss and plaque formation.

PMID- 15485484
TI  - Non-steroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease: old and
      new mechanisms of action.
AB  - Alzheimer's disease (AD) is characterized by cerebral deposits of beta-amyloid (A
      beta) peptides and neurofibrillary tangles (NFT) which are surrounded by
      inflammatory cells. Epidemiological studies have shown that prolonged use of non
      steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD and
      delays the onset of the disease. It has been postulated that some NSAIDs target
      pathological hallmarks of AD by interacting with several pathways, including the
      inhibition of cyclooxygenases (COX) and activation of the peroxisome proliferator
      activated receptor gamma. A variety of experimental studies indicate that a
      subset of NSAIDs such as ibuprofen, flurbiprofen, indomethacin and sulindac also
      possess A beta-lowering properties in both AD transgenic mice and cell cultures
      of peripheral, glial and neuronal origin. While COX inhibition occurs at low
      concentrations in vitro (nM-low microm range), the A beta-lowering activity is
      observed at high concentrations (< or = 50 microm). Nonetheless, studies with
      flurbiprofen or ibuprofen in AD transgenic mice show that the effects on A beta
      levels or deposition are attained at plasma levels similar to those achieved in
      humans at therapeutic dosage. Still, it remains to be assessed whether adequate
      concentrations are reached in the brain. This is a crucial aspect that will allow
      defining the dose-window and the length of treatment in future clinical trials.
      Here, we will discuss how the combination of anti-amyloidogenic and anti
      inflammatory activities of certain NSAIDs may produce a profile potentially
      relevant to their clinical use as disease-modifying agents for the treatment of
      AD.

PMID- 15485485
TI  - Functional importance of the C-terminus of the human norepinephrine transporter.
AB  - Three C-terminal variants of the human norepinephrine transporter (hNET) are
      known: the wild-type hNET in which exon 14 encodes the last seven amino acids and
      two variants with either three or 18 amino acids encoded by an alternatively
      spliced exon 15. In transfected HEK293 cells we compared by means of
      [(3)H]norepinephrine ([(3)H]NE) uptake and [(3)H]nisoxetine ([(3)H]NIS) binding
      the functional properties of the wild-type hNET with those of the more abundant
      long splice variant containing exon 15 (hNET-Ex15L) and of two artificial hNET
      mutants lacking either the last three (hNET-Ex14-4) or all seven (hNET-Ex14-0) C
      terminal amino acids of exon 14. No differences among the NET isoforms were
      observed concerning the K(m) for uptake of NE and the K(D) for binding of NIS.
      However, compared with the wild-type hNET, the three isoforms (hNET-Ex15L, hNET
      Ex14-4 and hNET-Ex14-0) showed a pronounced decrease in V(max) of [(3)H]NE uptake
      and B(max) of [(3)H]NIS binding which correlated with strongly reduced surface
      expression of the transporter isoforms. The decrease in surface expression of the
      hNET isoforms is probably a consequence of the lack of the three amino acids
      leucine, alanine and isoleucine at the C-terminal end which may represent a motif
      facilitating cell surface expression of the hNET. Expression of hNET-Ex15L
      exerted a dominant negative effect on plasma membrane expression of the wild-type
      hNET and thus may represent a novel mechanism for regulation of noradrenergic
      neurotransmission.

PMID- 15485486
TI  - Up-regulation of the Kv3.4 potassium channel subunit in early stages of
      Alzheimer's disease.
AB  - Gene expression throughout the different stages of Alzheimer's disease was
      analysed in samples from cerebral cortex. The gene encoding the voltage-gated
      potassium channel Kv3.4 was already overexpressed in early stages of the disease,
      and in advanced stages Kv3.4 was present at high levels in neurodegenerative
      structures. This subunit regulates delayed-rectifier currents, which are primary
      determinants of spike repolarization in neurones. In unique samples from a
      patient with Alzheimer's disease whose amount of amyloid plaques was decreased by
      beta amyloid immunization, Kv3.4 was overexpressed. The channel subunit was
      expressed in the neuropil, in the remaining conventional plaques in the frontal
      cortex and in collapsed plaques in the orbitary cortex. Therefore, amyloid
      deposition in plaques does not seem to be responsible for the increase in Kv3.4
      levels. Nevertheless, Kv3.4 up-regulation is related to amyloid pathology, given
      that transgenic mice with the Swedish mutation of amyloid precursor protein
      showed increased expression of Kv3.4. Up-regulation of voltage-gated potassium
      channel subunits alters potassium currents in neurones and leads to altered
      synaptic activity that may underlie the neurodegeneration observed in Alzheimer's
      disease. Thus, Kv3.4 likely represents a novel therapeutic target for the
      disease.

PMID- 15485487
TI  - Nitric oxide-induced increase of excitatory amino acid levels in the trigeminal
      nucleus caudalis of the rat with tactile hypersensitivity evoked by the loose
      ligation of the inferior alveolar nerves.
AB  - To investigate whether or not N-methyl-D-aspartate (NMDA)/nitric oxide (NO)
      pathway in the trigeminal system is involved in the development and/or
      maintenance of such pathological pain states as the hyperalgesia and allodynia
      observed after dental surgery, we examined the alteration patterns of excitatory
      amino acid (EAA) level in the superficial layer of subnucleus caudalis of the
      brain-stem trigeminal sensory nuclear complex (SpVc-I,II) by in vivo
      microdialysis. A very high EAA release response was observed immediately after
      the start of the perfusion in ligated animals compared with sham-operated rats.
      The EAA level evoked by application of the 40-V tooth pulp-stimulation or 1%
      capsaicin cream was significantly higher in the ligated animals than those in the
      sham-operated animals. This increase of EAA level induced by capsaicin cream was
      inhibited by adding carboxy-PTIO (100 microM) to the perfusate. The applications
      of SNAP (2 mM) into the perfusate enhanced the level of EAAs in ligated animals
      and sham-operated animals. However, SNAP-evoked EAA levels in ligated animals
      were not significantly different compared with those of sham-operated animals.
      These results suggest that alterations in the stimulus-evoked raised EAA levels
      that occur in the site of the first synaptic relay of the dental pain pathway and
      which are expressed via endogenous NO, and which play an important role in
      development and/or maintenance of pathological pain states following dental
      peripheral nerve injury.

PMID- 15485488
TI  - Minocycline inhibits apoptotic cell death via attenuation of TNF-alpha expression
      following iNOS/NO induction by lipopolysaccharide in neuron/glia co-cultures.
AB  - We attempted to ascertain the neuroprotective effects and mechanisms of
      minocycline in inflammatory-mediated neurotoxicity using primary neuron/glia co
      cultures treated with lipopolysaccharide (LPS). Neuronal cell death was induced
      by treatment with LPS for 48 h, and the cell damage was assessed using lactate
      dehydrogenase (LDH) assays and by counting microtubule-associated protein-2 (MAP
      2) positive cells. Through terminal transferase deoxyuridine triphosphate-biotin
      nick end labeling (TUNEL)-staining and by measuring caspase-3 activity, we found
      that LPS-induced neuronal cell death was mediated by apoptosis. We determined
      that pre-treatment with minocycline significantly inhibited LPS-induced neuronal
      cell death. In addition, LPS induced inducible nitric oxide synthase (iNOS)
      expression significantly, resulting in nitric oxide (NO) production within glial
      cells, but not in neurons. Both nitric oxide synthase (NOS) inhibitors (N(G)
      monomethyl-L-arginine monoacetate (L-NMMA) and S-methylisothiourea sulfate (SMT))
      and minocycline inhibited iNOS expression and NO release, and increased neuronal
      survival in neuron/glia co-cultures. Pre-treatment with minocycline significantly
      inhibited the rapid and extensive production of tumor necrosis factor-alpha (TNF
      alpha) mediated by LPS in glial cells. We also determined that the signaling
      cascade of LPS-mediated iNOS induction and NO production was mediated by TNF
      alpha by using neutralizing antibodies to TNF-alpha. Consequently, our results
      show that the neuroprotective effect of minocycline is associated with inhibition
      of iNOS induction and NO production in glial cells, which is mediated by the LPS
      induced production of TNF-alpha.

PMID- 15485489
TI  - Septin 3 (G-septin) is a developmentally regulated phosphoprotein enriched in
      presynaptic nerve terminals.
AB  - The septins are GTPase enzymes with multiple roles in cytokinesis, cell polarity
      or exocytosis. The proteins from the mammalian septin genes are called Sept1-10.
      Most are expressed in multiple tissues, but the mRNA for Sept5 (CDCrel-1) and
      Sept3 (G-septin) appear to be primarily expressed in brain. Sept3 is
      phosphorylated by cGMP-dependent protein kinase I (PKG-I) and the cGMP/PKG
      pathway is involved in presynaptic plasticity. Therefore to determine whether
      Sept3 specifically associates with neurones and nerve terminals we investigated
      its distribution in rat brain and neuronal cultures. Sept3 protein was detected
      only in brain by immunoblot, but not in 12 other tissues examined. Levels were
      high in all adult brain regions, and reduced in those enriched in white matter.
      Expression was developmentally regulated, being absent in the early embryo, low
      in late embryonic rat brain and increasing after birth. Like dynamin I, Sept3 was
      specifically enriched in synaptosomes compared with whole brain, and was only
      found in a peripheral membrane extract and not in the soluble or membrane
      extracts. Sept3 was particularly abundant in mossy fibre nerve terminals in the
      hippocampus. In primary cultured hippocampal neurones Sept3 immunoreactivity was
      punctate in neurites and predominantly localized to presynaptic terminals,
      strongly colocalizing with synaptophysin and dynamin I. The specific nerve
      terminal localization was confirmed by immunogold electron microscopy. Together
      this shows that Sept3 is a neurone-specific protein highly enriched in nerve
      terminals which supports a secretory role in synaptic vesicle recycling.

PMID- 15485491
TI  - Evaluation of 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-(1-methyl-2-(S)
      pyrrolidinylmethoxy)pyridine and its analogues as PET radioligands for imaging
      nicotinic acetylcholine receptors.
AB  - A novel series of compounds derived from the high-affinity nicotinic
      acetylcholine receptor (nAChR) ligand, 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-((1
      methyl-2-(S)-pyrrolidinyl)methoxy)pyridine (Me-p-PVC), originally developed by
      Abbott Laboratories, was characterized in vitro in nAChR binding assays at 37
      degrees C to show K(i) values in the range of 9-611 pm. Several compounds of this
      series were radiolabeled with (11)C and evaluated in vivo in mice and monkeys as
      potential candidates for PET imaging of nAChRs. [(11)C]Me-p-PVC (K(i) =56 pm at
      37 degrees C; logD = 1.6) was identified as a radioligand suitable for the in
      vivo imaging of the alpha 4 beta 2* nAChR subtype. Compared with 2-[(18)F]FA, a
      PET radioligand that has been successfully used in humans and is characterized by
      a slow kinetic of brain distribution, [(11)C]Me-p-PVC is more lipophilic. As a
      result, [(11)C]Me-p-PVC accumulated in the brain more rapidly than 2-[(18)F]FA.
      Pharmacological evaluation of Me-p-PVC in mice demonstrated that the toxicity of
      this compound was comparable with or lower than that of 2-FA. Taken together,
      these results suggest that [(11)C]Me-p-PVC is a promising PET radioligand for
      studying nAChR occupancy by endogenous and exogenous ligands in the brain in
      vivo.

PMID- 15485490
TI  - Modulation of NMDA receptor function by cyclic AMP in cerebellar neurones in
      culture.
AB  - The signal transduction pathways involved in NMDA receptor modulation by other
      receptors remain unclear. cAMP could be involved in this modulation. The aim of
      this work was to analyse the contribution of cAMP to NMDA receptor modulation in
      cerebellar neurones in culture. Forskolin increases cAMP and results in increased
      intracellular calcium and cGMP that are prevented by blocking NMDA receptors.
      Similar effects were induced by two cAMP analogues, indicating that cAMP leads to
      NMDA receptor activation. It has been reported that phosphorylation of Ser897 of
      the NR1 subunit of NMDA receptors by cAMP-dependent protein kinase (PKA)
      activates the receptors. Forskolin increases Ser897 phosphorylation. Neither
      Ser897 phosphorylation nor cGMP increase induced by forskolin are prevented by
      four inhibitors of PKA, suggesting that NMDA receptor activation is dependent on
      cAMP but not on PKA. Inhibition of Akt prevents forskolin-induced phosphorylation
      of Ser897, suggesting a role for Akt in the mediation of the modulation of NMDA
      receptors by cAMP. Pituitary adenylate cyclase-activating polypeptide (PACAP)
      activates its receptors, increasing cAMP and also leading to phosphorylation of
      Ser897 of NR1 and activation of NMDA receptors. These results indicate that cAMP
      modulates NMDA receptor in cerebellar neurones and may play a role in NMDA
      receptor modulation by other receptors.

PMID- 15485492
TI  - HaRas activates the NADPH oxidase complex in human neuroblastoma cells via
      extracellular signal-regulated kinase 1/2 pathway.
AB  - In this study we have investigated the effects of the small GTP-binding-protein
      Ras on the redox signalling of the human neuroblastoma cell line, SK-N-BE stably
      transfected with HaRas(Val12). The levels of reactive oxygen species (ROS) and
      superoxide anions were significantly higher in HaRas(Val12) expressing (SK-HaRas)
      cells than in control cells. The treatment of cells with 4-(2-aminoethyl)
      benzenesulfonylfluoride, a specific inhibitor of the membrane superoxide
      generating system NADPH oxidase, suppressed the rise in ROS and significantly
      reduced superoxide levels produced by SK-HaRas cells. Moreover, HaRas(Val12)
      induced the translocation of the cytosolic components of the NADPH oxidase
      complex p67(phox) and Rac to the plasma membrane. These effects depended on the
      mitogen-activated protein kinase kinase/extracellular signal-regulated kinase
      (MEK/ERK1/2) pathway, as the specific MEK inhibitor, PD98059, prevented HaRas
      mediated increase in ROS and superoxide anions. In contrast, the specific
      phosphoinositide 3-kinase (PI3K) inhibitors LY294002 and wortmannin were unable
      to reverse the effects of HaRas(Val12). Moreover, cholinergic stimulation of
      neuroblastoma cells by carbachol, which activated endogenous Ras/ERK1/2, induced
      a significant increase in ROS levels and elicited membrane translocation of
      p67(phox) and Rac. ROS generation induced by carbachol required the activation of
      ERK1/2 and PI3K. Hence, these data indicate that HaRas-induced ERK1/2 signalling
      selectively activates NADPH oxidase system in neuroblastoma cells.

PMID- 15485493
TI  - Macrophage colony stimulatory factor and interferon-gamma trigger distinct
      mechanisms for augmentation of beta-amyloid-induced microglia-mediated
      neurotoxicity.
AB  - Dysregulated stimulation of microglia, the resident macrophages in the brain, can
      lead to excessive induction of inflammatory agents and subsequently damage to
      neurons. Fibrillar beta-amyloid peptide (fA beta), a major component of senile
      plaques in Alzheimer's disease (AD) brain, is known to induce microglial-mediated
      neurotoxicity under certain conditions. Microglial 'priming' by macrophage colony
      stimulatory factor (MCSF) or interferon-gamma (IFN gamma) appears to be required
      for this fA beta-induced microglia mediated neurotoxicity in vitro. We report
      here that while both MCSF and IFN gamma induce microglial-mediated fA beta
      neurotoxicity, their mechanisms of toxicity differ. The enhancement of
      neurotoxicity by IFN gamma or MCSF is not due to enhanced A beta ingestion by
      microglia or to the direct effect of proinflammatory cytokine production. The
      neurotoxicity resulting from IFN gamma/fA beta treatment was blocked by
      pretreatment with nitric oxide synthase inhibitor L-N-5-(1-iminoethyl) ornithine
      hydrochloride (L-NIO), consistent with a role for nitric oxide in the IFN gamma
      mediated toxicity mechanism. In contrast, no induction of nitric oxide production
      was detected for microglia treated with MCSF/fA beta. Furthermore, inhibiting the
      generation of reactive oxygen species (ROS) using the specific NADPH oxidase
      inhibitor apocynin reversed fA beta/MCSF-induced neurotoxicity while L-NIO had
      little effect. As MCSF is endogenously expressed within the brain, and both its
      level and that of the MCSF receptor are dramatically increased in the AD brain,
      the neurotoxicity resulting from ROS release by fA beta/MCSF coactivated
      microglia may be a more appropriate model for assessing fA beta-induced
      microglial-mediated neuropathology in AD.

PMID- 15485494
TI  - Induction of cyclin-dependent kinase 5 and its activator p35 through the
      extracellular-signal-regulated kinase and protein kinase A pathways during
      retinoic-acid mediated neuronal differentiation in human neuroblastoma SK-N
      BE(2)C cells.
AB  - Cyclin-dependent kinase 5 (Cdk5), a neuronal Cdc2-like kinase, exhibits a variety
      of functions in neuronal differentiation and neurocytoskeleton dynamics, as well
      as neuronal degeneration. However, its role and induction mechanisms in retinoic
      acid (RA)-induced neuronal differentiation have not been well understood. In this
      study we newly found that RA treatment of SK-N-BE(2)C, human neuroblastoma cells,
      increased the expression of Cdk5 and its neuron specific activator p35 through
      the extracellular-signal-regulated kinase1/2 (ERK1/2) and cAMP-dependent protein
      kinase A (PKA) pathway. Inhibition of Cdk5 activity either by an inhibitor,
      roscovitine, or by transfection with a dominant negative form of Cdk5 caused a
      dramatic decrease in RA-induced differentiation, suggesting the requirement of
      Cdk5 kinase activity for the RA-induced neurite outgrowth. Furthermore, Cdk5 and
      p35 expression was decreased by ERK1/2 inhibition with PD98059 and increased by
      overexpression of a constitutive active mitogen-activated protein kinase kinase 1
      (MEK1) mutant, suggesting the critical role of ERK1/2 in the induction of Cdk5
      and p35. In addition, a transcription factor early growth response 1 (Egr-1) was
      induced by RA through the ERK1/2 pathway, suggesting its possible involvement in
      the p35 induction. RA treatment also induced c-fos mediated AP-1 binding, and
      cAMP-responsive element binding protein (CREB) mediated CRE binding via ERK1/2
      and PKA pathway, respectively, in the Cdk5 promoter region, resulting in the
      induction of Cdk5. Our results suggest that ERK1/2 and PKA-induced regulation of
      Cdk5 activity possibly through Egr-1, c-fos, and CREB plays a critical role in
      the RA-induced neuronal differentiation.

PMID- 15485495
TI  - Detecting bioactive amyloid beta peptide species in Alzheimer's disease.
AB  - Amyloid beta peptide (A beta) is believed to play a central role in the
      pathogenesis of Alzheimer's disease (AD). However, the form of A beta that
      induces neurodegeneration in AD, defined here as bioactive A beta, is not clear.
      Preventing the formation of bioactive A beta or inactivating previously formed
      bioactive A beta should be a promising approach to treat AD. We have previously
      developed a cell-based assay for the detection of bioactive A beta species. The
      assay is based upon the correlation between the ability of an A beta sample to
      induce a unique form of cellular MTT [3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide] formazan exocytosis, and its ability to activate
      glia and induce neurotoxicity. Here, we show that this cell-based assay is not
      only useful for a cellular model of A beta amyloidogenesis but is also able to
      detect bioactive A beta species in a transgenic mouse model of AD, as well as in
      post-mortem cortex samples from AD patients. There is a good correlation between
      the extent of glia activation and the level of bioactive A beta species in the
      mouse brain. A promising deuteroporphyrin that can inactivate bioactive A beta
      species was also identified using this assay. These novel insights and findings
      should have important implications for the treatment of AD.

PMID- 15485496
TI  - Differential modulation of evoked and spontaneous glycine release from rat spinal
      cord glycinergic terminals by the cyclic AMP/protein kinase A transduction
      cascade.
AB  - The mechanisms underlying cyclic AMP modulation of action potential-dependent and
      -independent (spontaneous) release of glycine from terminals synapsing onto
      sacral dorsal commissural nucleus neurons of lamina X were studied in spinal cord
      slices using conventional patch-clamp recordings. 3-Isobutyl-1-methylxanthine
      (IBMX), a phosphodiesterase inhibitor, and forskolin increased the amplitude of
      evoked inhibitory postsynaptic currents (eIPSCs) in a sensitive manner to protein
      kinase A (PKA) inhibition (with KT-5720). Direct activation (with adenosine 3',5'
      cyclic-monophosphothioate, Sp-isomer) and inhibition (with adenosine 3',5'-cyclic
      monophosphothioate, Rp-isomer) of PKA increased and decreased the eIPSC
      amplitude, respectively. Paired pulse experiments and direct injection of PKA
      inhibitor fragment 6-22 amide (PKI(6-22)) into the recording neuron revealed that
      these effects on eIPSC amplitude occurred presynaptically, indicating that evoked
      glycine release is regulated by presynaptic cAMP via changes in PKA activity.
      Increasing cAMP also increased spontaneous release of glycine, causing an
      increased frequency of miniature IPSCs (mIPSCs). In contrast to the effects on
      evoked release, this response was not solely mediated via PKA, as it was not
      occluded by PKA inhibition, and both direct inhibition and direct activation of
      PKA actually enhanced mIPSC frequency. Direct inhibition of cAMP (with SQ 22536)
      did, however, reduce mIPSC frequency. These results suggest cAMP modulation of
      evoked and spontaneous release involves different presynaptic mechanisms and
      proteins.

PMID- 15485497
TI  - Role of extracellular signal-regulated protein kinase in neuronal cell death
      induced by glutathione depletion in neuron/glia mesencephalic cultures.
AB  - To date, glutathione (GSH) depletion is the earliest biochemical alteration shown
      in brains of Parkinson's disease patients, but the role of GSH in dopamine cell
      survival is debated. In this study we show that GSH depletion, produced with GSH
      synthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO), induces selectively
      neuronal cell death in neuron/glia, but not in neuronal-enriched midbrain
      cultures and that cell death occurs with characteristics of necrosis and
      apoptosis. BSO produces a dose- and time-dependent generation of reactive oxygen
      species (ROS) in neurons. BSO activates extracellular signal-regulated kinases
      (ERK-1/2), 4 and 6 h after treatment. MEK-1/2 and lipoxygenase (LOX) inhibitors,
      as well as ascorbic acid, prevent ERK-1/2 activation and neuronal loss, but the
      inhibition of nitric oxide sintase (NOS), cyclo-oxygenase (COX), c-Jun N-terminal
      kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) does not have
      protective effects. Co-localization studies show that p-ERK-1/2 expression after
      BSO treatment increased in astrocytes and microglial cells, but not in neurons.
      Selective metabolic impairment of glial cells with fluoroacetate decreased ERK
      activation. However, blockade of microglial activation with minocycline did not.
      Our results indicate that neuronal death induced by GSH depletion is due to ROS
      dependent activation of the ERK-1/2 signalling pathway in glial cells. These data
      may be of relevance in Parkinson's disease, where GSH depletion and glial
      dysfunction have been documented.

PMID- 15485498
TI  - Autoreceptor-mediated inhibition of norepinephrine release in rat medial
      prefrontal cortex is maintained after chronic desipramine treatment.
AB  - Alterations in noradrenergic neurotransmission are important in the mechanism of
      action of many antidepressant drugs, including selective norepinephrine (NA)
      reuptake inhibitors such as desipramine (DMI). It has been suggested that chronic
      NA reuptake blockade induces a desensitization of inhibitory alpha(2)-adrenergic
      autoreceptors. This hypothesis was tested in experiment 1 using in vivo
      microdialysis to examine the degree of alpha(2)-autoreceptor-mediated inhibition
      of NA release in rat medial prefrontal cortex exerted by endogenous NA following
      chronic treatment with vehicle or DMI. This was accomplished by measuring the
      elevation of extracellular NA levels induced by acute administration of the
      alpha(2)-receptor antagonist yohimbine. An 8-fold increase in basal NA levels was
      observed after 21 days of DMI treatment. Further, acute yohimbine administration
      induced a robust elevation in NA levels which was not attenuated, and in fact at
      lower doses was greater in DMI-treated rats compared with vehicle-treated
      controls. In experiment 2, we addressed directly the functional status of
      terminal alpha(2)-autoreceptors in frontal cortex in vitro, in the absence of
      potentially confounding competition from elevated levels of endogenous NA, after
      chronic reuptake blockade. We observed no difference in the degree to which the
      alpha(2)-receptor agonist clonidine inhibited potassium-evoked [(3)H]-NA release
      from cortical slices taken from DMI- or vehicle-treated rats. Together, these
      data suggest that endogenous activation of alpha(2)-autoreceptors persists in
      restraining NA neurotransmission in the face of tonically elevated basal NA
      levels following chronic reuptake blockade.

PMID- 15485499
TI  - ShcA regulates neurite outgrowth stimulated by neural cell adhesion molecule but
      not by fibroblast growth factor 2: evidence for a distinct fibroblast growth
      factor receptor response to neural cell adhesion molecule activation.
AB  - Homophilic binding in trans of the neural cell adhesion molecule (NCAM) mediates
      adhesion between cells and leads, via activation of intracellular signaling
      cascades, to neurite outgrowth in primary neurons as well as in the neuronal cell
      line PC12. NCAM mediates neurite extension in PC12 cells by two principal routes
      of signaling: NCAM/Fyn and NCAM/fibroblast growth factor receptor (FGFR),
      respectively. Previous studies have shown that activation of mitogen-activated
      protein kinases is a pivotal point of convergence in NCAM signaling, but the
      mechanisms behind this activation are not clear. Here, we investigated the
      involvement of adaptor proteins in NCAM and fibroblast growth factor 2 (FGF2)
      mediated neurite outgrowth in the PC12-E2 cell line. We found that both FGFR
      substrate-2 and Grb2 play important roles in NCAM as well as in FGF2-stimulated
      events. In contrast, the docking protein ShcA was pivotal to neurite outgrowth
      induced by NCAM, but not by FGF2, in PC12 cells. Moreover, in rat cerebellar
      granule neurons, phosphorylation of ShcA was stimulated by an NCAM mimicking
      peptide, but not by FGF2. This activation was blocked by inhibitors of both FGFR
      and Fyn, indicating that NCAM activates FGFR signaling in a manner distinct from
      FGF2 stimulation, and regulates ShcA phosphorylation by the concerted efforts of
      the NCAM/FGFR as well as the NCAM/Fyn signaling pathway.

PMID- 15485500
TI  - Distribution and localization of pro-brain-derived neurotrophic factor-like
      immunoreactivity in the peripheral and central nervous system of the adult rat.
AB  - The precursors for neurotrophins are proteolytically cleaved to form biologically
      active mature molecules which activate their receptors p75NTR and trks. A recent
      study showed that the precursor for nerve growth factor (NGF) can bind to p75NTR
      with a high affinity and induces apoptosis of neurons in vitro. Mutation in
      Val66Met of brain-derived neurotrophic factor (BDNF) results in reduction in
      hippocampal function in learning and in the dysfunction of intracellular BDNF
      sorting and secretion. To examine the functions of pro-neurotrophins in vivo, it
      is essential to know where they are expressed in the nervous system. In the
      present study, we have raised and characterized rabbit polyclonal antibodies
      against a peptide coding for the precursor region of the BDNF gene. The antibody
      specifically recognizes the precursor for BDNF by western blot. With the affinity
      purified precursor antibody, we have mapped the distribution and localization of
      the precursor for BDNF. The results showed that, like mature BDNF, pro-BDNF is
      localized to nerve terminals in the superficial layers of dorsal horn, trigeminal
      nuclei, nuclei tractus solitarius, amygdaloid complex, hippocampus, hypothalamus
      and some peripheral tissues. These results suggest that pro-BDNF, like mature
      BDNF, is anterogradely transported to nerve terminals and may have important
      functions in synaptic transmission in the spinal cord and brain.

PMID- 15485501
TI  - A role for semaphorin 3A signaling in the degeneration of hippocampal neurons
      during Alzheimer's disease.
AB  - Among the earliest invariant neuropathological changes in Alzheimer's disease
      (AD) is the degeneration of vulnerable hippocampal CA1 and subicular pyramidal
      neurons. Semaphorin 3A (Sema3A) is a secreted protein that functions in signaling
      growth cone collapse, chemorepulsion and neuronal apoptosis during early
      development of the central nervous system. In this report we show that
      accumulation of an internalized form of Sema3A is associated with degeneration of
      neurons in vulnerable fields of the hippocampus during AD. Accumulation of Sema3A
      overlaps the appearance of phosphorylated MAP1B and tau in many neurons,
      suggesting that Sema3A signaling at some level may be coupled to these previously
      identified cytoskeletal markers of neurodegeneration. Consistent with this, we
      isolated and partially characterized a multiprotein complex from the hippocampus
      of patients with AD that contains phosphorylated MAP1B, collapsin-response
      mediator protein 2 (CRMP-2), Plexins A1 and A2, and a processed form of Sema3A. A
      model is presented in which aberrant release of Sema3A from expressing neurons in
      the subiculum during AD results in the internalization and transport of Sema3A
      from this field to CA1. Within the context of the myriad of potential insults
      that contribute to Alzheimer's and other neurodegenerative diseases, the
      bioactivity of Sema3A may contribute either directly to neurodegeneration by
      inducing neuronal collapse, or indirectly by abrogating the recovery capabilities
      of adult neurons faced with these insults.

PMID- 15485502
TI  - P311 accelerates nerve regeneration of the axotomized facial nerve.
AB  - In axotomized adult neurons, a process of axonal regrowth and re-establishment of
      the neuronal function has to be activated. Developmentally regulated factors may
      be reactivated during neuronal regeneration. Here we identify a gene, previously
      designated P311, that is up-regulated in the axotomized facial motoneurons.
      Ectopically expressed P311 localizes in the cytoplasm and the nucleus. Over
      expression of P311 induces p21(WAF1/Cip1) expression, leading PC12 cells to
      differentiate and to have neuron-like morphologies. Adenovirus-mediated P311 gene
      transfer promotes neurite outgrowth of postnatal dorsal root ganglion neurons and
      embryonic hippocampal neurons in vitro. This effect is abolished by the
      activation of Rho kinase. P311 also facilitates nerve regeneration following
      facial nerve injury in vivo. Our data provide evidence that genes involved in the
      differentiation process contribute to the regeneration of injured mature neurons,
      and may provide a practical molecular target.

PMID- 15485503
TI  - Ca2+/calmodulin-dependent protein kinase II is reversibly autophosphorylated,
      inactivated and made sedimentable by acute neuronal excitation in rats in vivo.
AB  - Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is highly enriched in the
      central nervous system, and is proposed to play important roles in activity
      dependent modifications of neuronal functions. We reported previously on the
      dynamic regulation of the autonomous CaMKII in homogenates from hippocampus and
      parietal cortex by acute neuronal excitation induced by electroconvulsive
      treatment (ECT) in rats in vivo. In the present study, we examined in more detail
      the biochemical changes in CaMKII under such conditions. We unexpectedly found a
      concurrent increase in autophosphorylation at Thr286(alpha)/287(beta) and
      decrease in the specific activity of CaMKII in the particulate fraction in either
      hippocampus or parietal cortex during ECT-induced acute, brief seizure activity.
      On the other hand, the soluble CaMKII showed a marked decrease in
      autophosphorylation with unchanged or rather increased specific activity.
      Increased autophosphorylation and decreased CaMKII activity were associated with
      the detergent-insoluble particulate fraction. All these changes disappeared soon
      after the termination of seizure activity. The reversible formation of such an
      autophosphorylated, inactivated and sedimentable form of CaMKII during acute
      neuronal excitation may indicate the existence of a novel regulatory mechanism of
      CaMKII that may be important for normal functioning of the brain.

PMID- 15485504
TI  - Pyrrolidine dithiocarbamate inhibits translocation of nuclear factor kappa-B in
      neurons and protects against brain ischaemia with a wide therapeutic time window.
AB  - Pyrrolidine dithiocarbamate (PDTC) is an antioxidant and inhibitor of
      transcription factor nuclear factor kappa-B (NF-kappa B). Because the role of NF
      kappa B in brain injury is controversial and another NF-kappa B inhibiting
      thiocarbamate, DDTC, was recently shown to increase ischaemic brain damage, we
      investigated the effect of PDTC on transient brain ischaemia. Ischaemia was
      induced by occlusion of the middle cerebral artery (MCAO). In Wistar rats, the
      PDTC treatment started even 6 h after MCAO reduced the infarction volume by 48%.
      PDTC protected against MCAO also in spontaneously hypertensive rats and against
      forebrain ischaemia in Mongolian gerbils. PDTC prevented NF-kappa B activation in
      the ischaemic brain as determined by reduced DNA binding and nuclear
      translocation of NF-kappa B in neurons. PDTC had anti-inflammatory effect by
      preventing induction of NF-kappa B-regulated pro-inflammatory genes. In ischaemic
      rats, NF-kappa B was localized in cyclo-oxygenase-2-immunoreactive neurons. Blood
      cytokine levels were not altered by ischaemia or PDTC. When cultured neurons were
      exposed to an excitotoxin, no production of reactive oxygen species was detected,
      but PDTC provided protection and prevented nuclear translocation of NF-kappa B.
      The clinically approved PDTC and its analogues may act as anti-inflammatories and
      may be safe therapies in stroke with a wide time window.

PMID- 15485505
TI  - Choline is transported by vesicular acetylcholine transporter.
AB  - Previously published results appeared to show that vesicular acetylcholine
      transporter (VAChT) does not transport choline (Ch). Because it is uniquely
      suited to detect transport of weakly bound substrates, a recently developed assay
      that detects transmembrane reorientation of the substrate binding site was used
      to re-examine transport selectivity. Rat VAChT was expressed in PC12(A1237)
      cells, postnuclear supernatant-containing microvesicles was prepared, and the
      reorientation assay was conducted with unlabeled Ch and tetramethylammonium
      (TMA). Also, [(14)C]Ch and [(3)H]acetylcholine (ACh) were used in an optimized
      accumulation assay. The results demonstrate that Ch is transported at least as
      well as ACh is, but with sevenfold lower affinity. Even TMA is transported, but
      with 26-fold lower affinity. Ch transport by VAChT is of interest in view of the
      possibilities that Ch (i) occurs at higher concentration than ACh does in
      terminal cytoplasm under some conditions, and (ii) is an agonist for alpha 7
      nicotinic receptors.

PMID- 15485506
TI  - Noninvasive electrocardiology has come of age.

PMID- 15485507
TI  - Signal-averaged P wave duration and the dimensions of the atria.
AB  - BACKGROUND: Delay of atrial electrical conduction measured as prolonged signal
      averaged P wave duration (SAPWD) could be due to atrial enlargement. Here, we
      aimed to compare different atrial size parameters obtained from echocardiography
      with the SAPWD measured with a signal-averaged electrocardiogram (SAECG).
      METHODS: In 74 patients scheduled for elective echocardiography, an SAECG was
      recorded directly after the echocardiogram. We measured the SAPWD and registered
      clinical characteristics. The correlation between the SAPWD and the left atrial
      diameter (LAD), left atrial volume (LAV), right atrial volume (RAV), and total
      atrial volume (TAV) was analyzed by linear regression analyses. The effect of
      concomitant risk factors on TAV and the SAPWD was examined. RESULTS: Linear
      regression analysis showed that the correlation between the SAPWD and the LAD was
      significant (R(2)= 0.11, P = 0.03). However, LAV (R(2)= 0.15, P = 0.009), RAV
      (R(2)= 0.27, P = 0.0003), and TAV (R(2)= 0.37, P < 0.0001) were more strongly
      correlated to the SAPWD. The TAV and the SAPWD were not significantly associated
      with coexisting risk factors. CONCLUSIONS: The SAPWD is significantly correlated
      to the atrial size; most strongly to the TAV. The size of the right atrium, with
      the sinus node area, appears to affect the SAPWD.

PMID- 15485508
TI  - Wavelet-based analysis of heart-rate-dependent ECG features.
AB  - BACKGROUND: Wavelet-based methods of analyzing ECG signals have been used to
      identify specific features in cardiac arrhythmias. Since some of these features
      are rate dependent, it is a requirement that they are examined across a range of
      physiological heart rates. The wavelet transform is a signal analysis tool that
      can elucidate spectral and temporal information simultaneously from complex
      signals, including the ECG. The aim of this study was to identify the local
      frequency characteristics of the ECG using a real-time wavelet scalogram and to
      study the rate dependence of these features. METHODS: We examined the spectral
      temporal behavior of the local characteristics of the electrocardiogram (ECG) of
      10 patients, in whom precise control of heart rate was achieved using right
      atrial pacing. Temporary reprogramming was used to adjust the paced atrial rate
      to predetermined values so that a rate-controlled rhythm was produced that
      closely resembled sinus rhythm. RESULTS: Rate-dependent features are seen on time
      frequency scalograms. As the rate increases, the temporal spacing of features
      decrease and the frequency bands shift upward on the plot. Two patients with
      abnormal atrioventricular conduction demonstrate features of Wenckebach
      conduction and fusion. CONCLUSIONS: Characterization of the rate-dependent
      features of the ECG in a paced atrial rhythm by wavelet transform techniques has
      revealed some additional information not readily seen on single lead ECG
      analysis. This model provides a surrogate for changes that might be expected
      during rate changes in physiological sinus rhythm. It is envisaged that this
      method will offer advantages in detecting features of clinical significance that
      may not be readily seen by existing methods.

PMID- 15485509
TI  - Beat-to-beat heart rate and QT variability in patients with congestive cardiac
      failure: blunted response to orthostatic challenge.
AB  - BACKGROUND: Congestive cardiac failure is associated with increased sympathetic
      activity and impaired baroreflex function. We sought to test the hypothesis that
      these patients also have blunted response of beat-to-beat QT interval variability
      during orthostatic challenge. METHODS: We compared beat-to-beat heart rate and QT
      interval data in 17 patients with congestive cardiac failure and 17 age-matched
      normal controls in supine normal breathing, supine controlled breathing, and
      standing controlled breathing conditions. The ECG data were acquired in lead II
      configuration at a sampling rate of 1000 Hz. RESULTS: Supine controlled breathing
      was associated with an increase in spectral HF power (0.15-0.5 Hz) of HR and QT
      interval time series compared to spontaneous breathing condition only in
      controls. While there were significant changes in HR, HR LF power, HR LF/HF
      ratios, and QT variability measures in standing posture in controls, there were
      no such changes in patients. CONCLUSIONS: This impairment of postural changes of
      HR variability is most likely due to an impaired baroreceptor function in
      patients with congestive heart failure. The etiology of this is likely due to an
      increased cardiac sympathetic and a decreased vagal function. However, the
      relationship of postural changes in beat-to-beat QT interval variability and
      baroreflex need further investigation.

PMID- 15485510
TI  - Association of stage of left ventricular diastolic dysfunction with P wave
      dispersion and occurrence of atrial fibrillation after first acute anterior
      myocardial infarction.
AB  - OBJECTIVES: The aim of this study was to investigate the association of stage of
      left ventricular diastolic dysfunction after acute myocardial infarction (AMI)
      with P maximum, P dispersion, and atrial fibrillation (AF) occurrence rate.
      BACKGROUND: The occurrence of AF following AMI is frequently associated with a
      left ventricle restrictive filling pattern. Increased P dispersion is also
      associated with the occurrence of AF after AMI. But, the relation between the
      stage of left ventricular diastolic dysfunction and the P wave measurements after
      AMI has not yet been investigated. METHODS: Electrocardiograms of 90 patients
      with first anterior AMI were recorded on admission, and P wave measurements were
      performed. The left ventricular diastolic functions were evaluated by
      transthoracic echocardiography. On the basis of mitral inflow, subjects were
      stratified into three left ventricular diastolic filling patterns. All patients
      were monitored continuously for the detection of AF in the Coronary Care Unit.
      RESULTS: Thirty patients had a normal filling pattern (33.3%) (NF group), 37 had
      impaired relaxation (41.1%) (IR group), and 23 had pseudonormal/restrictive
      filling pattern (25.6%) (PN/R group). P maximum was longer in the PN/R group (103
      +/- 12 ms) compared with the NF group (94 +/- 9 ms, P = 0.019), but no
      significant difference was found between PN/R and IR (96 +/- 13 ms, P > 0.05)
      groups, and between NF and IR groups (P > 0.05). There was no significant
      difference for P minimum among the groups (P > 0.05). P dispersion was longer in
      the PN/R group (35 +/- 6 ms) than in the NF (26 +/- 7 ms, P < 0.001) and IR
      groups (26 +/- 6 ms, P < 0.001), but not different between the NF and IR groups
      (P > 0.05). Occurrence of AF was significantly more frequent in the PN/R group
      (52.2%) than in the NF (16.7%, P = 0.007) and IR groups (10.8%, P = 0.001).
      Frequency of AF was not different between the NF and IR groups (P > 0.05). In
      multivariate analyses, the stage of diastolic dysfunction was independently
      associated with P maximum, P minimum, P dispersion, and the occurrence of AF (P <
      0.001, P = 0.035, P < 0.001, and P = 0.002, respectively). CONCLUSIONS: P maximum
      and P dispersion are increased, and AF occurrence risk is higher in patients with
      pseudonormal/restrictive filling pattern after first anterior AMI. The stage of
      diastolic dysfunction is an independent predictor of P wave measurements and AF
      occurrence.

PMID- 15485511
TI  - The significance of P wave duration and P wave dispersion for risk assessment of
      atrial tachyarrhythmias in patients with corrected tetralogy of Fallot.
AB  - BACKGROUND: The aim of the present study was to determine the potential role of P
      wave duration and P wave dispersion for risk assessment of atrial
      tachyarrhythmias in patients with corrected tetralogy of Fallot (ToF). METHODS:
      The maximum P wave duration, minimum P wave duration, and the P wave dispersion
      from the 12-lead surface electrocardiogram of the patients and controls were
      measured. Electrophysiological study was performed only in the patient group.
      RESULTS: The study group consisted of 25 patients with corrected ToF with a mean
      age of 16.4 +/- 4.25 years and 25 age-matched healthy control subjects. Patients
      underwent repair at a mean age of 4.6 +/- 3.41 years (range: 1-19), and the mean
      duration of follow-up of 11.8 +/- 1.7 years (range: 9-15) after surgery. On
      electrophysiological study sinus node dysfunction was detected in 3 patients
      (12%), atrial tachyarrythmias-atrial flutter or fibrillation-in 5 patients (20%),
      both sinus node dysfunction and atrial flutter in 1 patient (4%), and AV
      conduction delay in 1 patient (4%). P wave dispersion is significantly higher in
      patients with atrial tachyarrhythmia inducible by electrophysiological study than
      in other patients (P < 0.05). A P wave dispersion value of >35 ms has a high
      predictive accuracy (sensitivity = 83% and specificity = 89%) for inducible
      atrial tachyarrhythmia in patients with corrected tetralogy of Fallot.
      CONCLUSION: P wave dispersion is an easily measured electrocardiographic marker
      with a good sensitivity and specificity for predicting atrial arrhythmias in
      patients after correction of ToF.

PMID- 15485512
TI  - Evaluation of left atrial appendage functions in patients with thrombus and
      spontaneous echo contrast in left atrial appendage by using color Doppler tissue
      imaging.
AB  - OBJECTIVE: Thrombus and spontaneous echo contrast (SEC) develops in the left
      atrial appendage (LAA) when LAA function is disturbed. Decrease of left atrial
      appendage emptying velocity shows LAA dysfunction. The purpose of this study is
      to examine the incidence of SEC and/or thrombus in LAA in patients with acute
      myocardial infarction and to assess the LAA function using color Doppler tissue
      imaging (CDTI) of the patients with detected SEC and/or thrombus. METHOD AND
      RESULTS: Eighty-four patients with acute myocardial infarction were included in
      the study. Spontaneous echo contrast and/or thrombus were observed in 24 (29%) of
      the 84 patients who were categorized as group 1 (mean age 59 +/- 12 years). Sixty
      patients (71%) without thrombus and/or SEC in LAA were categorized as group 2
      (mean age 58 +/- 8 years). Left atrial diameters and left ventricular ejection
      fraction were measured by using transthoracic echocardiography. Left atrial
      appendage emptying and LAA filling velocity were measured by transesophageal
      Doppler echocardiography. Systolic appendage tissue velocities (SaV cm/s) were
      measured at the basal, mid, and tip of medial wall of LAA by transesophageal
      CDTI. Group 1 had significantly decreased LAA emptying velocities, mid SaVs, and
      left ventricular ejection fractions compared to group 2 (37 +/- 9 cm/s vs 55 +/-
      22 cm/s, 3.1 +/- 1.6 cm/s vs 3.7 +/- 1.2 cm/s, and 47 +/- 13% vs 58 +/- 10%,
      respectively, P = 0.002, P = 0.04, P = 0.03). Group 1 had significantly increased
      left atrial diameters compared to group 2 (40 +/- 5 mm vs 36 +/- 6 mm P = 0.001).
      Left atrial appendage-filling velocities, basal SaVs and tip SaVs in group 1 were
      lower than those in group 2 but not significantly. CONCLUSIONS: Mid-SaV of LAA
      medial wall and LAA emptying velocity decrease in patients with thrombus and/or
      SEC were an indication of functional disorder of LAA. Color Doppler tissue
      imaging appears to be a clinically applicable and reliable imaging technique that
      allows quantitative assessment of regional LAA systolic function.

PMID- 15485513
TI  - Sympathetic overactivity in patients with rheumatic mitral stenosis.
AB  - BACKGROUND: Mitral stenosis may increase sympathetic nervous activity by
      increasing left atrial pressure and reducing cardiac output. And elevated
      sympathetic nerve activity may be a risk factor for the development of clinical
      manifestations of mitral stenosis. In this study, we assessed the autonomic
      nervous system activity in patients with mitral stenosis by heart rate
      variability analysis and defined factors affecting autonomic functions. METHODS
      AND RESULTS: Fifty-four patients with rheumatic mitral stenosis were compared
      with an age- and gender-matched control group composed of 42 healthy individuals.
      SDNN, RMSSD, PNN50, and HF were lower; mean heart rate (HR), LF and LF/HF ratio
      were higher in the patients with mitral stenosis compared to the control group.
      SDNN was correlated positively with left ventricle ejection fraction (LVEF),
      negatively with mitral valve area, left atrial (LA) diameter, and duration of
      symptoms. RMSSD was correlated positively with mean transmitral gradient,
      negatively correlated with age; PNN50 was correlated negatively with mitral valve
      area and positively correlated with transmitral gradient. LF was positively and
      HF was negatively correlated with LA diameter; LF was correlated positively, and
      HF was negatively correlated with duration of symptoms. LF/HF ratio was
      positively correlated with LA diameter and duration of symptoms, negatively with
      LVEF and mean valve area. CONCLUSION: As a result, sympathetic nervous system
      activity is increased in patients with mitral stenosis and sympathetic
      overactivity worsens their symptoms. Most significant factors that affect
      autonomic functions in these patients are left atrial dilatation and mitral valve
      area.

PMID- 15485514
TI  - Why a sawtooth? Inferences on the generation of the flutter wave during typical
      atrial flutter drawn from radiofrequency ablation.
AB  - BACKGROUND: Typical atrial flutter (AFL) is a macroreentrant arrhythmia
      characterized by a counterclockwise circuit that passes through the cavotricuspid
      isthmus with passive depolarization of the left atrium. These electrical events
      are thought to be responsible for the classic "sawtooth" wave of atrial flutter
      seen on the surface electrocardiogram characterized by a gradual downward
      deflection followed by a sharp negative deflection. It has been suggested that
      the negative flutter wave is a result of passive depolarization of the left
      atrium. We hypothesized that interruption of the circuit within the isthmus would
      prevent the reentrant wave from depolarizing the left atrium thus eliminating the
      component of the electrocardiogram reflecting left atrial depolarization.
      METHODS: We examined 100 cases of atrial flutter with the typical "sawtooth"
      pattern referred for radiofrequency ablation. Ninety-seven of the 100 were
      successfully ablated. All cases were reviewed for termination of atrial flutter
      with the last intracardiac electrogram just lateral to the site of linear
      ablation and surface flutter wave at the moment of termination not obscured by
      the QRS segment or the T-wave. Seventeen of the 97 met these criteria. RESULTS:
      Seventeen of the 17 cases demonstrated a gradual negative deflection as the last
      discernible wave of atrial activity followed by an isoelectric period and
      resumption of normal sinus rhythm. The last generated wave lacked the sharp
      negative downstroke. CONCLUSION: These results suggest that the sharp negative
      deflection of flutter waves likely correlates with the wavefront's penetration of
      the interatrial septum and passive depolarization of the left atrium.

PMID- 15485515
TI  - Left bundle branch block in type 2 diabetes mellitus: a sign of advanced
      cardiovascular involvement.
AB  - OBJECTIVE: To evaluate left bundle branch block (LBBB) as an indicator of
      advanced cardiovascular involvement in diabetic (DM) patients by examining left
      ventricular systolic function and proteinurea. METHODS: Data of 26 diabetic
      patients with left bundle branch block (DM with LBBB) were compared with data of
      31 diabetic patients without left bundle branch block (DM without LBBB) and 18
      nondiabetic patients with left bundle branch block (non-DM with LBBB). The
      inclusion criteria were age >45 years, and diabetes mellitus type 2 of >5 years.
      RESULTS: Mean ages of patients in DM with LBBB, DM without LBBB, and non-DM with
      LBBB groups were 67 +/- 8, 68 +/- 10, and 65 +/- 10 years, respectively (P = NS).
      Females were 65%, 61%, and 61%, respectively (P = NS). Left ventricular ejection
      fraction in DM with LBBB was significantly lower than in DM without LBBB and non
      DM with LBBB (30 +/- 10% vs 49 +/- 12% and 47 +/- 8%, P < 0.01). Left ventricular
      end-diastolic volume was significantly higher in DM with LBBB than in DM without
      LBBB and non-DM with LBBB (188.6 +/- 16.4 mL vs 147.5 +/- 22.3 mL and 165.3 +/-
      15.2 mL, P < 0.03). Similarly, left ventricular end-systolic volume was
      significantly higher in DM with LBBB than in DM without LBBB and non-DM with LBBB
      (135.4 +/- 14.7 mL vs 83.7 +/- 9.5 mL and 96.6 +/- 18.4 mL, P < 0.02). No
      statistically significant difference was seen in left atrial size. Proteinurea in
      DM with LBBB (79.4 +/- 18.9 mg/dL) was significantly higher than in DM without
      LBBB (35.6 +/- 8.5 mg/dL, P < 0.05) and non-DM with LBBB (12 +/- 3.5 mg/dL, P <
      0.05); however, there was no significant difference in Hb A1c levels in DM with
      LBBB and DM without LBBB (9.01% vs 7.81%, P = NS). CONCLUSIONS: Left bundle
      branch block in diabetic patients indicates advanced cardiovascular involvement
      manifesting with more severe left ventricular systolic dysfunction and
      proteinurea compared to both diabetic patients without left bundle branch block
      and nondiabetic patients with left bundle branch block.

PMID- 15485516
TI  - Estrogen and progestin use and the QT interval in postmenopausal women.
AB  - OBJECTIVE: To determine whether menopausal hormone therapy alters the QT interval
      in primarily healthy postmenopausal women. BACKGROUND: Despite well-known gender
      differences in myocardial repolarization that include a longer heart-rate
      corrected QT interval (QT(C)) in women compared to men, the effects of menopausal
      hormone therapy on myocardial repolarization in women have not been well
      characterized. METHODS: We studied 34,378 postmenopausal women participating in
      the dietary intervention component of the Women's Health Initiative. Cross
      sectional associations were examined to assess possible effects of estrogen +
      progesterone on myocardial repolarization. Women who reported that they were
      never treated with menopausal hormone therapy (n = 12,451) were compared to women
      with a past use of menopausal hormone therapy (n = 3891), currently taking
      unopposed estrogen therapy (n = 9987), or combined current estrogen and
      progesterone therapy (n = 8049). RESULTS: Using analysis of covariance, the mean
      (+/-SEM) QT(C) interval was 423.1 +/- 0.2 milliseconds (ms) in those never
      treated with menopausal hormone therapy, 423.9 +/- 0.3 ms in past menopausal
      hormone therapy users, 425.6 +/- 0.2 ms in those currently on estrogen alone, and
      424.0 +/- 0.2 ms in women currently on combined estrogen-progesterone therapy.
      Differences in mean QT(C) between those on estrogen alone and the other three
      groups were statistically significant. Comparisons of JT intervals, QT intervals,
      and linear corrected QT intervals among the groups yielded similar results.
      CONCLUSION: These results suggest that unopposed estrogen in menopausal women
      mildly prolongs myocardial repolarization, and the effect is reversed by
      progesterone. Whether these findings have clinical significance requires further
      study.

PMID- 15485517
TI  - QT interval dispersion analysis in patients undergoing left partial
      ventriculectomy (Batista operation).
AB  - BACKGROUND: QT interval dispersion (QTd) has been valued as a marker of increased
      vulnerability for cardiac arrhythmias. QTd was analyzed in patients undergoing
      the left partial ventriculectomy (LPV) or Batista operation, a palliative surgery
      for patients in the line for heart transplantation, which is associated with
      complex arrhythmia and death from sustained ventricular tachyarrhythmia (SVT).
      METHODS: Pre- and postoperative R-R, QT, QTc, JT (QT - QRS), and aT (apex to end
      of T wave) intervals were obtained by 87-lead body surface mapping from 24
      patients (18 male), mean age 46.4 +/- 9.15 years. Dispersions of QT, QTc, JT, and
      aT intervals were calculated, and the total number of arrhythmic events were
      assessed, aiming to verify a possible risk predictor for the occurrence of SVTs.
      Subgroups of patients who survived and who died after LPV were also compared,
      aiming to obtain a QTd cutoff value that could be used prognostically. RESULTS:
      No difference between pre- and postoperative mean values were found, but a very
      significant difference was seen when comparing QTd and QTcD values for surviving
      and dead patients: QTd, cutoff value was 95 ms, while QTcD value was 114 ms.
      CONCLUSION: There were no significant differences between pre- and postoperative
      variables or the number of arrhythmic events, but there were significant
      differences between both pre- and postoperative QTd and QTcD data from surviving
      and dead patients; this enabled the determination of cutoff values that we
      believe may be useful for the prognosis of the LPV outcome.

PMID- 15485518
TI  - New criteria based on ST changes in 12-lead surface ECG to detect proximal versus
      distal right coronary artery occlusion in a case of acute inferoposterior
      myocardial infarction.
AB  - BACKGROUND: The outcome of patients with inferoposterior myocardial infarction
      (MI) due to occlusion of right coronary artery (RCA) depends mainly on the
      location of occlusion (distal vs. proximal). The aim of this study was to
      evaluate the value of new ECG criteria: the sum of ST depression in I and VL
      leads and ST changes in V1 lead to predict the location of RCA occlusion in the
      case of an inferoposterior MI. METHODS: The ECG and angiographical findings of 50
      patients with acute inferoposterior MI due to RCA occlusion were analyzed. The
      value of new criteria was studied alone and in combination to predict proximal
      versus distal RCA occlusion and compared with previously described criterion
      based only on ST changes in VL. RESULTS: Isoelectric or elevated ST in V1 allowed
      predicting proximal RCA occlusion with 70% sensitivity and 87% specificity with
      high positive and negative predictive value (87% and 71%, respectively). The new
      criterion of the sum of ST depression in I and VL >or= 5.5 mm compared to the
      criterion based only on ST depression in VL was also more specific (91% vs. 72%)
      for proximal RCA occlusion with better positive and negative predictive values.
      CONCLUSIONS: The new criterion based on the ST changes in V1 lead is highly
      accurate in detecting the location of occlusion in the RCA compared to the
      criteria based only on ST changes in lateral leads. The use of this criterion
      might increase the accuracy of ECG-based identification of myocardial involvement
      in acute inferoposterior MI.

PMID- 15485519
TI  - QRS subtraction and the ECG analysis of atrial ectopics.
AB  - The recognition of the ubiquitous role of short coupled ectopics in the
      initiation of paroxysmal atrial fibrillation has renewed interest in their
      localization with the ultimate aim of facilitating their neutralization by
      catheter ablation. The P-waves resulting from such ectopics are partly or
      completely concealed by the QRST of the preceding beat and therefore their
      morphology has been underutilized for localization purposes. Subtraction has been
      the most commonly used technique for QRST suppression and though an averaged
      template offers a higher signal-to-noise ratio, the immediately preceding QRST
      provides the best match between template and target and allows simple, nearly
      real-time, and accurate subtraction without distorting the underlying P-wave.
      Algorithms derived from clinical tachycardias as well as pacemapping have
      permitted a rational analysis and accurate prediction (81%) of the correct
      pulmonary vein of origin. Other nonpulmonary sources may also be similarly
      localized, particularly with the help of a catalogue of pacemaps from various
      sites. Incessant arrhythmia and frequent aberrancy limit the effectiveness of
      QRST suppression by subtraction. Further improvements in the localizing
      resolution of the P-wave may depend upon knowledge of the relationship between
      recording electrodes and the underlying atria.

PMID- 15485520
TI  - Introductory note to a classic article on the auriculo-ventricular bundle by
      Keith and Flack.

PMID- 15485521
TI  - The auriculo-ventricular bundle of the human heart. 1906.

PMID- 15485522
TI  - Unusual evolution of ST elevation acute myocardial infarction.
AB  - We report a case of acute ST-segment elevation myocardial infarction with an
      unusual evolution of ST-segment elevation. Several possible explanations of this
      progression are discussed with supportive evidence for each explaination. The
      clinical, electrocardiographic, and angiographic features of this case are also
      illustrated.

PMID- 15485523
TI  - Hormones, fluid retention, and ST segment changes.

PMID- 15485524
TI  - Tetracycline and other tetracycline-derivative staining of the teeth and oral
      cavity.
AB  - Tetracyclines (TCN) were introduced in 1948 as broad-spectrum antibiotics that
      may be used in the treatment of many common infections in children and adults.
      One of the side-effects of tetracyclines is incorporation into tissues that are
      calcifying at the time of their administration. They have the ability to chelate
      calcium ions and to be incorporated into teeth, cartilage and bone, resulting in
      discoloration of both the primary and permanent dentitions. This permanent
      discoloration varies from yellow or gray to brown depending on the dose or the
      type of the drug received in relation to body weight. Minocycline hydrochloride,
      a semisynthetic derivative of tetracycline often used for the treatment of acne,
      has been shown to cause pigmentation of a variety of tissues including skin,
      thyroid, nails, sclera, teeth, conjunctiva and bone. Adult-onset tooth
      discoloration following long-term ingestion of tetracycline and minocycline has
      also been reported. The remarkable side-effect of minocycline on the oral cavity
      is the singular occurrence of "black bones", "black or green roots" and blue-gray
      to gray hue darkening of the crowns of permanent teeth. The prevalence of
      tetracycline and minocycline staining is 3-6%. The mechanism of minocycline
      staining is still unknown. Most of the reviewed literature consisted of case
      reports; longitudinal clinical trials are necessary to provide more information
      on the prevalence, severity, etiology and clinical presentation of tetracycline
      and TCN-derivative staining in the adult population.

PMID- 15485525
TI  - Piebaldism: an update.

PMID- 15485526
TI  - Sweet's syndrome revealing relapsing polychondritis.
AB  - Sweet's syndrome is extremely rare in relapsing polychondritis. We report a rare
      case of Sweet's syndrome revealing relapsing polychondritis. A 77-year-old man
      presented with fever, associated with respiratory symptoms and non pruritic,
      painful, erythematous, papules and plaques mainly on the arms and legs. Skin
      biopsy of the arm found a neutrophilic dermal infiltrate consistent with Sweet's
      syndrome. A month and a half after admission, the patient presented with ear
      chondritis and dysphonia. Biopsy of the ear cartilage found a significant
      perichondral inflammatory cells infiltrate. The diagnosis of relapsing
      polychondritis was established and a steroid treatment was instituted with a
      complete regression of the cutaneous signs and chondritis.

PMID- 15485527
TI  - Immunohistochemical study of serotonin in lesions of chronic eczema.
AB  - BACKGROUND: Inflammatory mediators participate in the pathogenesis and
      pathophysiology of skin disease (e.g. eczema). Although some investigators have
      suggested that serotonin may participate in the eczematous process, there has
      been little substantial evidence. Our objective was to study further the
      participation of serotonin in the pathogenesis of chronic eczema. METHODS:
      Immunohistochemical techniques were used to study the expression of serotonin in
      the lesions of patients with chronic eczema. RESULTS: There was a significantly
      stronger expression of serotonin in the prickle cells, sweat gland cells,
      sebaceous gland cells, and hair roots of the lesions in patients with chronic
      eczema. There was no positive expression of serotonin in normal skin.
      CONCLUSIONS: Serotonin is probably important in the pathogenesis of chronic
      eczema. We demonstrated alterations in the expression of serotonin in chronic
      eczema lesions, which may in turn provide new insight into the pathogenesis of
      chronic eczema. Serotonin, along with cytokines, T lymphocytes, B lymphocytes,
      and macrophages, participates in the immune response and influences the
      inflammatory process by means of keratinocytes.

PMID- 15485528
TI  - Epidemiology of cutaneous tuberculosis in Japan: a retrospective study from 1906
      to 2002.
AB  - BACKGROUND: Interest in tuberculosis has recently been revived, especially in
      association with the onset of acquired immunodeficiency syndrome (AIDS). In
      Japan, the incidence of tuberculosis has declined since the 1950s, but has shown
      a tendency to increase in the past 10 years. METHODS: To determine the patterns
      of prevalence of cutaneous tuberculosis in Japan, data for cutaneous tuberculosis
      cases recorded between 1906 and 2002 were obtained from the dermatologic clinic
      of Kyushu University Hospital. The population of tuberculosis-infected patients
      was stratified into groups encompassing 10-year periods. Each patient group was
      then classified as having true tuberculosis or tuberculid, as well as being
      classified by gender. The total number of patients with cutaneous tuberculosis
      analyzed was 1324. RESULTS: The incidence of cutaneous tuberculosis, both true
      tuberculosis and tuberculid, decreased between 1906 and 1935, increased between
      1936 and 1955, and decreased again from 1955. The incidence of true tuberculosis
      was higher than that of tuberculid between 1906 and 1925. The incidence rates of
      true tuberculosis and tuberculid were equal from 1926 to 1945, and since 1946 the
      incidence of tuberculid has been higher than that of true tuberculosis. The
      incidence of tuberculid decreased between 1986 and 1995, but showed a dramatic
      increase between 1996 and 2000. The frequency of cutaneous tuberculosis was
      highest in the 10-49 year age group before 1980, but since 1981 has been highest
      in groups over 40 years of age. CONCLUSIONS: The incidence of cutaneous
      tuberculosis in Japan is decreasing and shows a shift towards older generations.
      However, there is an increase in the incidence of tuberculid, especially in
      elderly female patients.

PMID- 15485529
TI  - Granulocyte adsorptive apheresis for leg ulcers complicated by rheumatoid
      arthritis: a report on three successfully treated cases.
AB  - BACKGROUND: The treatment of inflammatory leg ulcers complicated by rheumatoid
      arthritis (RA), which are unresponsive to conventional care, can be frustrating.
      Furthermore, as granulocytes and monocytes (GM) are major sources of inflammatory
      cytokines, they have the potential to initiate and perpetuate inflammatory skin
      lesions. Accordingly, a recent study reported the remission of pyoderma
      gangrenosum following the reduction of activated peripheral blood GM by
      adsorptive apheresis (GMA). METHODS: In this clinical study, we applied GMA to
      three cases, each with one leg ulcer below the knee and RA. The ulcers had not
      responded to conventional therapy, including disinfection, dressing, and
      antimicrobials, and therefore were thought to represent inflammatory vasculitic
      lesions. GMA was performed using a column with a capacity of 335 mL, filled with
      cellulose acetate beads that selectively adsorb granulocytes and
      monocytes/macrophages (Adacolumn). Each patient received one GMA session/week for
      five consecutive weeks. The duration of one session was 60 min, with a flow rate
      of 30 mL/min. RESULTS: The ulcers began to recede after two GMA sessions and, by
      the end of the fifth session, the ulcers in all three patients had healed. No
      recurrence has been observed up to the time of this report. The treatment was
      well tolerated and no severe side-effects were observed. CONCLUSIONS: GMA, which
      depletes activated neutrophils and monocytes/macrophages, appears to be effective
      for inflammatory skin ulcers which do not respond to conventional medications.

PMID- 15485531
TI  - Current epidemiology of atopic dermatitis in south-eastern Nigeria.
AB  - BACKGROUND: Atopic dermatitis (AD) is a common pruritic, eczematous skin disorder
      that runs a chronic and relapsing course. In Nigeria, it is currently on the
      increase, particularly amongst infants, and has created cost burdens for
      families. It occurs in association with a personal or family history of asthma,
      allergic rhinitis and conjunctivitis. Major and minor criteria exist as
      guidelines for arriving at a diagnosis of AD, and surveys from Western countries
      have shown that these features, in particular the minor features, vary with
      ethnicity and genetic background and can be used to aid diagnosis. African
      dermatologists have also voiced concern that the much used Hanifin criteria for
      diagnosis of AD may need some adaptation for use in Africa. OBJECTIVE: To
      document the features and disease outcomes of AD seen amongst dermatology
      hospital patients in Enugu, south-eastern Nigeria, with a view to reflecting
      current features amongst Nigerian Blacks. METHODS: A prospective study of AD
      patients seen over a 2-year period at a tertiary referral dermatology clinic
      (University of Nigeria Teaching Hospital, Enugu, Nigeria) was carried out. A
      total of 1019 patients aged between 4 weeks and 57 years were included in the
      study. RESULTS: The prevalence of AD was 8.5%, which is much higher than the
      prevalence of AD reported in various parts of Nigeria 15 years ago. AD occurred
      before the age of 10 years in 523 (51.3%) patients, whilst 250 (24.5%) had onset
      after 21 years. The earliest age of onset in infants was in the first 6 weeks of
      life, and this was found in 129 patients (12.7%). Education and occupation of
      household heads were the most significant (P < 0.001) factors associated with
      seeking proper health care for the child's AD. Four hundred and forty-one (43.3%)
      patients presented with subacute atopic eczema and 326 (32%) patients with severe
      impeteginized eczema. Four hundred and twenty-five patients (41.7%) had at least
      one first-degree family member with AD (16.7%), allergic rhinitis (10.3%), asthma
      (14.6%) and allergic conjunctivitis (2.1%), while 55 (13.3%) of controls had a
      positive family history (P < 0.01) of allergy. A personal history of AD only,
      without concomitant respiratory allergies, was seen in 486 (47.7%) patients. The
      face was affected in 431 (42.3%) patients. Inverse distribution of a flexural
      rash was observed over the extensor aspect of the joints: the elbow in 502
      patients (49.3%), the wrist joint in 183 patients (17.9%) and the knee joints in
      354 patients (34.7). The commonly observed minor features included xerosis in 719
      patients (71%), papular lichenoid lesions in 547 patients (54.1%), infraorbital
      folds in 498 patients (49.2%), palmar hyper linearity in 524 patients (51.8%) and
      raised peripheral blood eosinophils in 519 patients (51%), particularly for those
      with severe AD. Fissured heels, forehead lichenification, orbital darkening, nail
      pitting, sand paper-like skin lesions on the elbows/knees/lateral malleolli,
      knuckle dermatitis of the hands, palmar erythema and pitted keratolysis occurred
      more uncommonly as minor features. Infective complications were very common and
      included bacterial infections (folliculitis, impetiginized dermatitis and
      pyodermas) in 425 (41.7%) patients, fungal infections in 377 (37%) patients,
      parasitic infections (scabies) in 90 (8.8%) patients and viral infection (herpes
      simplex and molluscum contagiosum) in 29 (2.9%) patients. Thirteen of these
      atopics were also HIV positive. Aggravating factors most commonly reported
      included heat intolerance, excessive sweating, humidity, grass intolerance, thick
      woollen clothing and drug reactions. Only three patients had food intolerance.
      Three hundred and ten patients (30.4%) recalled their AD being worse in the hot
      humid periods and 383 (37.6%) could not recall any periods of relief or
      remission. CONCLUSIONS: The prevalence of AD amongst south-eastern Nigerian
      Blacks is on the increase, as in other areas, although it is still lower here
      than in other parts of the world. Many conventional minor features were found,
      but some occurred less frequently than in other countries, which may be
      attributed to ethnicity. Further studies will be required to confirm the ethnic
      differences in these features of AD amongst Nigerians and other Africans, to
      clarify the features of AD that are peculiar to Africans.

PMID- 15485530
TI  - Evaluation of CO laser efficacy in the treatment of cutaneous leishmaniasis.
AB  - BACKGROUND: Cutaneous leishmaniasis is a common disease in Iran, especially in
      the north-east, central and southern parts of the country. Many treatments have
      been suggested for this disease but none is completely effective and without side
      effects such as pain, arthralgia and renal or cardiac complications. Lasers have
      been used for treatment of several skin diseases since 1970, and CO(2) lasers are
      now being used for treatment of leishmaniasis. In this study, a CO(2) laser
      (Sonic 500 machine) was used as a source of a continuous CO(2) laser wave.
      METHODS: A total of 123 patients (68 female and 55 male) with 183 lesions were
      treated with the CO(2) laser. The maximum power was 100 W and the pulse width was
      0.5-5 s. For the control group, 110 patients (with 250 lesions) were treated with
      glucantime 50 mg/kg/day for 15 days and, after 15 days of rest, this treatment
      was repeated (Glucantime Amps, 1.5 g in a 50-mL solution, was used). For follow
      up, the patients were visited 1, 3, 4, 8, 12 and 24 weeks after treatment and any
      complications, recurrences or other wound characteristics were recorded. In the
      second group, Finally, all collected data were analyzed statistically. RESULTS:
      Statistical analysis with the chi(2) test showed that treatment with the CO(2)
      laser was more effective than treatment with glucantime (P = 0.0007).
      Complications were also seen less often with the laser treatment than with
      glucantime and were limited to the ulcer site. The CO(2) laser was more effective
      in treating cutaneous leishmaniasis than glucantime (1.12 times), had fewer side
      effects (4.5% vs. 24%) and resulted in a shorter healing time (1 month vs. 3
      months), and treatment could be applied in a single session. CONCLUSIONS: The
      results of this and previous studies suggest that cutaneous leishmaniasis can be
      treated effectively with CO(2) laser if those providing the treatment are
      sufficiently experienced. Laser treatment is more cost-effective than other
      treatments and can be used as first-line therapy for cutaneous leishmaniasis (wet
      and dry types).

PMID- 15485532
TI  - Verrucous hemangioma.
AB  - A 13-year-old female presented complaining of swelling of the skin and purplish
      red papules and nodules on her left leg. These lesions had been present from
      early childhood and had slowly enlarged, increased in number, and become more
      verrucous. At the age of 8 years, one of the nodules had been excised by laser,
      but recurrence was noted within a few months. There was occasional pain and
      bleeding from the lesion. Physical examination revealed a group of several well
      circumscribed, hyperkeratotic, blue-red, vascular plaques arranged linearly along
      the inside aspect of her left lower extremity, ranging in size from 0.5 to 4.0 cm
      in diameter (Fig. 1). Smaller, discrete satellite nodules with a similar
      appearance were noted in the vicinity. Histopathologic examination showed
      hyperproliferation and hyperkeratosis of the epidermis. The superficial dermis
      showed multiple, thin-walled, dilated blood-filled spaces (Fig. 2). Similar
      spaces were present in the lower dermis and subcutaneous tissue. A diagnosis of
      verrucous hemangioma was made.

PMID- 15485533
TI  - Parvovirus B19 infections.
AB  - Abstract Parvovirus B19 infections cause a wide range of clinical findings,
      including erythema infectiosum, "glove-and-socks" syndrome, arthropathies, red
      cell aplasia, and intrauterine infections. The condition can be diagnosed
      serologically. The prognosis is excellent in healthy, immunocompetent
      individuals.

PMID- 15485534
TI  - Primary malignant melanoma of the oral cavity: a case report.
AB  - A 43-year-old white man was referred to the Special Care Dentistry Center of the
      School of Dentistry, University of Sao Paulo, Brazil, for the diagnosis of an
      extensive nodular lesion of the maxillary gingiva. The patient complained that
      his left maxilla had swollen over the last 4 months, with some exudation from the
      gingival crevice, sporadic bleeding, and slight tooth mobility, but no pain. An
      extra-oral examination confirmed expressive swelling of the left side of the face
      (Fig. 1A). Palpation disclosed bilateral enlargement of the submandibular lymph
      nodes. An intra-oral examination showed an extensive, reddish, nodular mass
      (around 11 cm in diameter) that extended from the last left maxillary molar to
      the right maxillary incisor, covered by a mucosa that was ulcerated in some areas
      (Fig. 1B,C). Palpation revealed a painless, soft, bleeding tissue that seemed to
      arise in the periodontal ligaments, extending to the palate and vestibular area.
      A small pigmented spot was found in the palatal mass. Histopathologically, the
      biopsy revealed a proliferation of neoplastic cells that exhibited a wide variety
      of shapes, including spindle, plasmacytoid, and epithelioid forms. The atypical
      cells showed enlarged and pleomorphic nuclei. Mitotic activity and pigmented
      areas were observed (Fig. 2A,B). Immunohistochemistry was used to establish the
      final diagnosis. The tumor cells strongly expressed S100 protein, gp100 (HMB-45),
      melan A, and tyrosine antibodies (Fig. 2C,D). With the diagnosis of malignant
      melanoma, the patient was referred to an oncologist for treatment. As computed
      tomography revealed that the lesion was deeply inserted into the skull surface
      (Fig. 1D), surgical intervention was not possible. The patient underwent
      radiotherapy, but died 14 months later.

PMID- 15485535
TI  - Itching stretch marks and bullous lesions in a pregnant woman.

PMID- 15485536
TI  - Insect bite-like reaction associated with mantle cell lymphoma: a report of two
      cases and review of the literature.
AB  - BACKGROUND: An insect bite-like reaction and exaggerated reactions to insect
      bites are nonspecific phenomena described primarily in association with chronic
      lymphocytic leukemia (CLL), but also with other hematological malignancies. Two
      cases of mantle cell lymphoma (MCL), one associated with an insect bite-like
      reaction and the other with a true hypersensitivity to mosquito bites, have
      previously been reported in the English language literature. The pathogenesis of
      the skin eruption may be related to the release of different cytokines that also
      trigger an IgE elevation and dermal eosinophils. CASE REPORT: We describe two
      additional cases of MCL associated with an insect bite-like reaction. One patient
      had been diagnosed with MCL 4.5 years prior to the appearance of the skin
      eruption, and in the other patient the skin symptoms preceded the diagnosis of
      the MCL by 2 years and led to its diagnosis. CONCLUSIONS: Insect bite-like
      reaction may appear in patients with MCL. It is important to recognize this
      entity because it may be the presenting sign of MCL.

PMID- 15485537
TI  - Formable acrylic treatment for ingrowing nail with gutter splint and sculptured
      nail.
AB  - BACKGROUND: The treatment of choice for an ingrowing nail has been surgical
      rather than nonsurgical. Yet, surgical treatments are far from successful, cause
      pain and patient apprehension, and leave disfigurement. Further, there is
      misunderstanding about the disease pathophysiology. OBJECTIVE: To demonstrate the
      benefits of a noninvasive method of treatment for an ingrowing nail using gutter
      splint and formable acrylics and to present a current understanding of the
      disease pathophysiology. METHODS: From a total of 541 cases of ingrowing nails
      treated, full follow-up data were obtained between January 1979 and March 2002.
      Formable acrylic treatments were carried out in 106 cases treated with acrylic
      affixed gutter splint, 17 cases with sculptured nails, and 28 cases in which the
      two treatments were combined. These were then compared with 233 cases treated
      with adhesive tape-attached gutter splint and the remainder with other
      conservative modalities. RESULTS: Acrylic treatment with gutter splint and
      sculptured nail was found to be vastly superior to the other methods described,
      especially in the ability to firmly affix the gutter splint and sculptured nail
      for the extended period required for treatment. The treatment leads to a complete
      remission with almost instant alleviation of pain, with no disfigurement, while
      allowing for the resumption of daily activities. CONCLUSION: Conservative methods
      utilizing formable acrylics are highly beneficial in the treatment of an
      ingrowing nail and should be viewed as the first treatment option.

PMID- 15485538
TI  - Acne treated successfully with azithromycin.
AB  - AIM: To study the efficacy, safety, and compliance of 500 mg azithromycin thrice
      weekly for 12 weeks in acne vulgaris. METHODS: An open-label, noncomparative
      study was carried out for 12 weeks at the outpatient clinics of Aga Khan
      University Hospital, Abassi Shaheed Hospital, and Burhani Community Hospital in
      Karachi, Pakistan. Thirty-five adolescent and postadolescent patients with
      moderate to severe papulopustular acne vulgaris were enrolled. All patients
      completed the study. Azithromycin, 500 mg orally thrice weekly for 12 weeks, was
      used. After the baseline visit, patients were scheduled to return at four-weekly
      intervals for 12 weeks. Efficacy was gauged by the percentage clearance of
      papulopustular acne lesions. Safety assessments included the monitoring of
      adverse events, and compliance was checked at the four-weekly regular visits up
      to 12 weeks. RESULTS: Twenty-nine patients (82.9%) showed remarkable improvement
      in the first 4 weeks with 60% reduction of their inflammatory papulopustular
      lesions. Maximum clearance (80%) was observed at 12 weeks. Residual
      postinflammatory pigmentation and pitted and linear scarring represented the
      aftermath of the relapsing pattern of acne. Six patients (17.1%) showed slow
      clearance with eruptions of new lesions. Adverse events, such as heartburn and
      nausea, were reported by four patients (11.4%). All patients completed the 12
      week study period. CONCLUSION: Azithromycin, 500 mg thrice weekly for 12 weeks,
      is a safe and effective treatment of acne vulgaris with excellent patient
      compliance.

PMID- 15485539
TI  - Pseudoporphyria as a result of voriconazole use: a case report.
AB  - Voriconazole, a second-generation triazole, has recently been approved by the
      Food and Drug Administration (FDA) to treat invasive aspergillosis and refractory
      infections with Scedosporium apiospermum or Fusarium spp. The reported side
      effects of voriconazole include visual changes, headaches, elevated hepatic
      enzymes, Steven-Johnson syndrome, toxic epidermal necrolysis, chelitis,
      photosensitivity, discoid lupus erythematosus and anaphylactoid infusion
      reactions. Pseudoporphyria was first described in association with nalidixic
      acid. It has the same clinical and histologic features as porphyria cutanea tarda
      (PCT) but is distinguished by normal porphyrin levels in the serum, urine and
      stool. We present the case of a patient who developed pseudoporphyria after
      receiving treatment with voriconazole.

PMID- 15485540
TI  - Sweet's syndrome and relapsing polychondritis: is their appearance in the same
      patient a coincidental occurrence or a bona fide association of these conditions?

PMID- 15485541
TI  - Skin hyperpigmentation induced by olanzapine, a novel antipsychotic agent.

PMID- 15485542
TI  - Herpes zoster and pruritus.

PMID- 15485543
TI  - Key dermatological symptoms in the intensive care unit.

PMID- 15485544
TI  - The impact of human immunodeficiency virus/acquired immunodeficiency syndrome
      (HIV/AIDS) on skin disease in KwaZulu-Natal, South Africa.

PMID- 15485546
TI  - Neuroprotective effects of melatonin against anoxia/aglycemia stress, as assessed
      by synaptic potentials and superoxide production in rat hippocampal slices.
AB  - Melatonin, which plays an important role in circadian rhythm regulation, is
      highly potent endogenous free radical scavenger and antioxidant. To clarify the
      neuroprotective effects of melatonin as a free radical scavenger, we recorded
      changes in synaptic potentials and monitored the generation of superoxide (O)(2)(
      ) (using hydroethidine) in the CA1 pyramidal layers of rat hippocampal slices
      exposed to anoxia/aglycemia ('ischemic') stress. Synaptic responses evoked by
      stimulation of Schaffer collateral/commissural afferents were suppressed by
      ischemic stress. When the duration of the stress was 8 min, the suppression was
      reversible, irrespective of the presence or absence of melatonin treatment, while
      the amount of O(2)(-) generated was reduced by the presence of melatonin. When
      stress duration was 12 min, the suppression of synaptic responses lasted more
      than 90 min, but melatonin significantly improved the recovery. The amount of
      O(2)(-) generated in the 'recirculation' phase after a 12 min ischemic stress was
      less in the ischemic alone group than in the melatonin-treated group. This
      probably reflects that the number of viable cells with the ability to generate
      O(2)(-) had been reduced by the more severe ischemic stress. Other radical
      scavengers (ascorbic acid and alpha-tocopherol) had similar effects. These
      results show that melatonin has the potential to protect the functions of neurons
      against an ischemic insult by reducing O(2)(-) generation.

PMID- 15485547
TI  - The stimulatory effect of mu- and delta-opioid receptors on bovine pinealocyte
      melatonin synthesis.
AB  - Mammalian pinealocytes synthesize and secrete melatonin. The synthesis of
      melatonin is regulated by several biogenic amine, amino acid and peptide
      transmitters. In our previous study, the delta- and mu-opioid receptors have been
      identified and characterized in bovine pinealocytes. In order to elaborate the
      function of different types of opioid receptors in regulating melatonin
      synthesis, we used a selective mu-opioid receptor agonist, Tyr-[D-Ala(2), N
      methyl-phe(4), glycol(5)] (DAMGO), a selective delta-opioid receptor agonist,
      Enkephalin [D-Pen(2), D-Pen(5)], (DPDPE) and a selective kappa-opioid receptor
      agonist, ((+)-(5alpha, 7alpha, 8beta)-N-methyl-N-[7- (1-pyrrolidinyl)-1-oxaspiro
      [4,5] dec-8-yl]-benzene acetamide) (U69593) to investigate the activity of N
      acetyltransferase (NAT) activity and melatonin secretion. The results of the
      present study show that both DAMGO and DPDPE stimulated NAT activity and
      increased the level of melatonin in cultured bovine pinealocytes. These
      stimulatory effects were blocked by naloxone, an opioid receptor antagonist.
      However, the kappa-opioid receptor agonist U69593 was unable to alter either the
      activity of NAT or the level of melatonin. In order to clarify the mechanism of
      how the activation of mu- and delta-opioid receptors in bovine pinealocytes leads
      to an increase in NAT activity, cyclic AMP levels were measured after bovine
      pinealocytes were treated with morphine, DAMGO and DPDPE. The results indicated
      that these stimulatory effects acted via induction of cAMP production. This study
      reveals that the stimulatory effect of opioid receptor on melatonin synthesis is
      mediated via the activation of adenylate cyclase system.

PMID- 15485548
TI  - Comparison of target innervation by sympathetic axons in adult wild type and
      heterozygous mice for nerve growth factor or its receptor trkA.
AB  - Nerve growth factor (NGF), a neurotrophin required for the survival and
      maintenance of postganglionic sympathetic neurons, mediates its trophic effects
      by activation of its high-affinity receptor trkA. Null mutant mice lacking either
      NGF or trkA have profound sympathetic deficits, thus revealing the vital
      importance of NGF synthesis in target tissues and trkA expression by sympathetic
      neurons. In this study, we sought to assess whether sympathetic neurons of the
      superior cervical ganglion (SCG) display alterations in their neurochemical
      phenotype in adult mice carrying one mutated allele for either NGF or trkA, and
      whether such differences result in altered patterns of innervation to the
      submandibular salivary gland and pineal gland. In comparison with adult siblings,
      levels of trkA protein in the SCG were reduced in age-matched NGF(+/-) and
      trkA(+/-) mice. While NGF(+/-) mice also had significantly fewer sympathetic
      axons innervating both the submandibular salivary gland and pineal gland,
      densities of sympathetic axons in both tissues reached normal levels in trkA(+/-)
      mice. These findings reveal that while levels of trkA are reduced in SCG neurons
      of adult NGF(+/-) and trkA(+/-) mice (compared with their wild type
      counterparts), sympathetic axons are capable of achieving normal patterns of
      target innervation in trkA(+/-) mice but not in NGF(+/-) mice. As NGF protein
      levels are not depleted in the submandibular salivary gland and pineal gland of
      NGF(+/-) mice, a loss of sympathetic neurons [Nat Neurosci 1999; 2:699-705], in
      combination with reduced levels of trkA protein, may account for perturbed
      patterns of sympathetic innervation to peripheral tissues.

PMID- 15485549
TI  - Melatonin protects against ionizing radiation-induced oxidative damage in corpus
      cavernosum and urinary bladder in rats.
AB  - The objective of this study was to examine the potential radioprotective
      properties of pharmacological doses of melatonin on corpus cavernosum and bladder
      tissues of whole-body irradiated (IR) rats. A total of 32 male Sprague-Dawley
      rats were exposed to irradiation performed with a LINAC which produced 6 MV
      photons at a focus 100 cm distant from the skin. Under ketamine anesthesia, each
      rat received a single whole-body dose of 800 cGy. Immediately before and after
      IR, rats were treated with either saline or melatonin (20 and 10 mg/kg, i.p.) and
      decapitated at 12 hr after exposure to irradiation. Another group of rats was
      followed for 72 hr after IR, where melatonin injections were repeated once daily.
      Tissue levels of malondialdehyde (MDA), an index of lipid peroxidation, and
      glutathione (GSH), a key antioxidant, were estimated in corpus cavernosum and
      urinary bladder. Tissues were also examined microscopically. The results
      demonstrate that both 12 and 72 hr following IR, tissue levels of MDA were
      elevated (P < 0.001), while GSH levels were reduced (P < 0.01) in both tissues.
      On the other hand, melatonin reversed these changes significantly (P < 0.05
      0.01), concomitant with the improvement in histological appearances. Our results
      show that whole-body irradiation causes oxidative damage in the tissues of the
      genitourinary system. As melatonin administration reversed oxidative organ
      injury, as assessed by biochemical and histopathological findings, it is
      suggested that supplementing cancer patients with adjuvant therapy of melatonin
      may have some benefit for successful radiotherapy.

PMID- 15485550
TI  - Prophylactic use of melatonin protects against focal cerebral ischemia in mice:
      role of endothelin converting enzyme-1.
AB  - Melatonin has previously been shown to be neuroprotective in rodent models of
      ischemic stroke. Herein, we tested whether this antioxidant may also be suitable
      for prophylactic use against stroke. To clarify this issue, melatonin was
      administrated orally for 9 wk (4 mg/kg/day) in mice and its effects on subsequent
      injury development after 90 min of intraluminal middle cerebral artery (MCA)
      occlusion were tested. To evaluate its neuroprotective properties, the protective
      actions of prophylactic melatonin were compared with both acute melatonin (4
      mg/kg, i.p.) administration and with a diluent (sham)-treated control condition.
      MCA occlusion resulted in reproducible ischemia, as revealed by laser Doppler
      flowmetry; this was followed by a rapid restoration of blood flow immediately
      after reperfusion onset. Laser Doppler flow values after reperfusion onset were
      moderately elevated by melatonin, both when the indole was given prophylactically
      and when acutely administrated after stroke. In control animals, reproducible
      brain infarcts were observed 24 hr after reperfusion onset. Treatment with
      melatonin significantly reduced the infarct size by approximately 30-35%,
      independent of whether the indole was given prophylactically before or acutely
      after ischemia. To test whether brain protection involved vascular mechanisms, as
      suggested earlier, the effects of melatonin on endothelin converting enzyme-1
      (ECE-1) levels were studied using Western blots. Interestingly, delivery of
      melatonin was accompanied by a marked inhibition of ECE-1 levels, which was
      similarly seen after both acute and chronic melatonin treatment. Our data suggest
      that melatonin, given at pharmacological doses, may be suitable as a prophylaxis
      against stroke. Tissue protection may involve an inhibition of ECE-1, which
      improves vasodilation, after ischemia.

PMID- 15485551
TI  - Protective effect of melatonin on 3-nitropropionic acid-induced oxidative stress
      in synaptosomes in an animal model of Huntington's disease.
AB  - The effect of melatonin (1 mg/kg BW i.p./day) on the oxidative changes produced
      by 3-nitropropionic acid (20 mg/kg BW/day for 4 days) in rat striatal and
      cortical synaptosomes was investigated. The effects of 3-nitropropionic acid were
      evaluated as changes in the quantity of lipid peroxidation products, protein
      carbonyl groups and superoxide dismutase and succinate dehydrogenase activities.
      3-Nitropropionic acid caused a rise in lipid peroxidation levels and protein
      carbonyls content whereas it induced a reduction in the activity of succinate
      dehydrogenase and triggered an enhancement in superoxide dismutase activity.
      These changes were prevented by previous administration of melatonin. Our results
      reveal: (i) 3-nitropropionic acid induces a status of oxidative stress in some
      brain regions of the Wistar rat; (ii) melatonin prevents the deleterious effects
      induced by the acid. In conclusion, the results show the ability of melatonin to
      modify the neural response to 3-nitropropionic acid with the protective mechanism
      likely involving the antioxidative processes of melatonin.

PMID- 15485552
TI  - Melatonin reduces amyloid beta-induced apoptosis in pheochromocytoma (PC12)
      cells.
AB  - The finding that the amyloid beta protein (Abeta) has neurotoxic properties and
      that such effects are partly mediated by free radicals has provided insights into
      the mechanisms of cell death in Alzheimer's disease (AD) and an avenue to explore
      new therapeutic approaches. Melatonin is a potent antioxidant and free radical
      scavenger. Previously, we showed that long-term application of melatonin
      alleviated the learning and memory deficits in the APP695 transgenic mouse model
      of AD. In this study, the importance of melatonin in the management of Abeta
      induced apoptosis was investigated. Rat pheochromocytoma (PC12) cells treated
      with either Abeta25-35 or Abeta1-42 underwent apoptosis. Melatonin pretreatment
      at 10(-5), 10(-6) and 10(-7) m significantly attenuated Abeta25-35- or Abeta1-42
      induced apoptosis in PC12 cells. The anti-apoptotic effects of melatonin were
      highly reproducible and corroborated by multiple quantitative methods, including
      MTT cell viability assay, Hoechst 33342 nuclei staining, DNA fragmentation
      analysis, and flow cytometric analysis. In addition, melatonin effectively
      suppressed Abeta1-42-induced nitric oxide formation, potently prevented Abeta1-40
      induced intracellular calcium overload and significantly alleviated Abeta1-40
      induced membrane rigidity. These results suggest that the mechanism of Abeta
      neurotoxicity involves oxidative stress, and the neuroprotective effects of
      melatonin are, at least in part, associated with its antioxidant properties. The
      use of melatonin or its derived analogs should be explored as a therapeutic
      approach in AD.

PMID- 15485554
TI  - Maternally administered melatonin protects against ischemia and reperfusion
      induced oxidative mitochondrial damage in premature fetal rat brain.
AB  - We investigated the oxidative susceptibility of the brain and the effect of
      maternally administered melatonin on ischemia/reperfusion-induced cerebral damage
      in premature fetal rat. Fetal brain mitochondria was separated on the 16th and
      19th days of pregnant rats and the respiratory control index (RCI) was measured
      as an indicator of mitochondrial respiratory activity in the presence or absence
      of xanthine and xanthine oxidase. The utero-ovarian arteries were occluded
      bilaterally for 20 min in female rats on day 16 of pregnancy to induce fetal
      ischemia. Reperfusion was achieved by releasing the occlusion and restoring
      circulation for 30 min. A sham operation was performed in control rats. Melatonin
      (10 mg/kg) or vehicle was injected intraperitoneally into the dams 60 min prior
      to occlusion. The RCI and concentration of thiobarbituric acid-reactive
      substances (TBARS) in fetal brain mitochondria were measured. The addition of
      xanthine and xanthine oxidase significantly decreased mitochondrial RCI at both
      the 16- and 19-day-old fetal brain. Xanthine and xanthine oxidase-induced
      reduction in RCI was significantly greater in the 16-day-old fetal brain than
      that in the fetal brain from the 19th day of pregnancy. Ischemia/reperfusion
      significantly reduced RCI and elevated TBARS concentrations in the 16-day-old
      fetal brain mitochondria. Melatonin treatment reversed ischemia/reperfusion
      induced reduction in RCI (2.22 +/- 0.10 to 2.53 +/- 0.08, P < 0.01) and elevation
      in TBARS concentrations (13.50 +/- 1.82 nmol/mg protein to 8.80 +/- 0.78 nmol/mg
      protein, P < 0.01), resulting in values similar to those in untreated, sham
      treated animals. Results indicate that brain mitochondria in the premature fetal
      rats appear to be more susceptible to oxidative damage. Melatonin administration
      to pregnant rats may prevent ischemia/reperfusion-induced oxidative mitochondrial
      damage in premature fetal brain.

PMID- 15485553
TI  - Melatonin protects against pancreaticobiliary inflammation and associated remote
      organ injury in rats: role of neutrophils.
AB  - Although the role of oxidative stress in acute pancreatitis (AP) has been studied
      in several animal models, little data are available regarding AP induced by
      pancreatic duct obstruction. We characterized the protective effects of melatonin
      on pancreaticobiliary inflammation and associated remote organ injury. In Sprague
      Dawley rats, either the common pancreaticobiliary duct (PBDL; n = 28) or bile
      duct (BDL; n = 28) was ligated or a sham operation was applied (n = 14). Either
      melatonin (10 mg/kg) or vehicle (saline; 1 mL/kg) was administered
      intraperitoneally (i.p.) immediately before the surgery and twice a day until the
      rats were decapitated at 6 or 72 h. The pancreas, liver, kidneys and lungs were
      removed and tissue samples were stored for the determination of malondialdehyde
      (MDA) and glutathione (GSH) levels and myelopreoxidase activity. The results
      demonstrate that pathogenesis of acute obstructive pancreatitis involves not only
      the oxidative damage of the pancreatic and hepatic tissues, as assessed by
      increased MDA and reduced GSH levels, but the lungs and kidneys are also
      challenged by oxidant injury. Similarly, hepatic oxidative injury caused by
      cholestasis was also accompanied by pulmonary, renal and even pancreatic damage.
      The biochemical findings were also verified histologically. Melatonin, probably
      because of its free-radical scavenging and antioxidant activity, which involves
      an inhibitory effect on tissue neutrophil infiltration, protected all the
      affected tissues.

PMID- 15485555
TI  - New indolicidin analogues with potent antibacterial activity.
AB  - Indolicidin is a 13-residue antimicrobial peptide amide, ILPWKWPWWPWRR-NH2,
      isolated from the cytoplasmic granules of bovine neutrophils. Indolicidin is
      active against a wide range of microorganisms and has also been shown to be
      haemolytic and cytotoxic towards erythrocytes and human T lymphocytes. The aim of
      the present paper is two-fold. First, we examine the importance of tryptophan in
      the antibacterial activity of indolicidin. We prepared five peptide analogues
      with the format ILPXKXPXXPXRR-NH2 in which Trp-residues 4,6,8,9,11 were replaced
      in all positions with X = a single non-natural building block; N-substituted
      glycine residue or nonproteinogenic amino acid. The analogues were tested for
      antibacterial activity against both Staphylococcus aureus American type culture
      collection (ATCC) 25923 and Escherichia coli ATCC 25922. We found that tryptophan
      is not essential in the antibacterial activity of indolicidin, and even more
      active analogues were obtained by replacing tryptophan with non-natural aromatic
      amino acids. Using this knowledge, we then investigated a new principle for
      improving the antibacterial activity of small peptides. Our approach involves
      changing the hydrophobicity of the peptide by modifying the N-terminus with a
      hydrophobic non-natural building block. We prepared 22 analogues of indolicidin
      and [Phe(4,6,8,9,11)] indolicidin, 11 of each, carrying a hydrophobic non-natural
      building block attached to the N-terminus. Several active antibacterial analogues
      were identified. Finally, the cytotoxicity of the analogues against sheep
      erythrocytes was assessed in a haemolytic activity assay. The results presented
      here suggest that modified analogues of antibacterial peptides, containing non
      natural building blocks, are promising lead structures for developing future
      therapeutics.

PMID- 15485556
TI  - Incorporation of vinylogous scaffolds in the C-terminal tripeptide of substance
      P.
AB  - Glycine-9 and leucine-10 of substance P (SP) are critical for (NK)-1 receptor
      recognition and agonist activity. Propsi(Z)-CH=CH(CH3)-CONH)Leu (or Met) and
      Propsi((E)-CH=CH(CH3)-CONH)Leu (or Met) have been introduced in the sequence of
      SP, in order to restrict the conformational flexibility of the C-terminal
      tripeptide, Gly-Leu-Met-NH2, of SP. Propsi((Z)-CH=C(CH2CH(CH3)2)-CONH)Met-NH2,
      with an isobutyl substituent to mimic the Leu side-chain, was also incorporated
      in place of the C-terminal tripeptide. The substituted-SP analogs were tested for
      their affinity to human NK-1 receptor specific binding sites (NK-1M and NK-1m)
      and their potency to stimulate adenylate cyclase and phospholipase C in Chinese
      Hamster ovary (CHO) cells transfected with the human NK-1 receptor. The most
      potent SP analogs [Pro9psi((Z)CH=C(CH3)CONH)Leu10]SP and [Pro9psi
      ((E)CH=C(CH3)CONH)Leu10]SP, are about 100-fold less potent than SP on both
      binding sites and second messenger pathways. These vinylogous (Z)- or (E)
      CH=C(CH3)- or (Z)-CH=C(CH2CH(CH3)2) moieties hamper the correct positioning of
      the C-terminal tripeptide of SP within both the NK-1M- and NK-1m-specific binding
      sites. The origin of these lower potencies is related either to an incorrect
      peptidic backbone conformation and/or an unfavorable receptor interaction of the
      methyl or isobutyl group.

PMID- 15485557
TI  - Synthesis and AT2 receptor-binding properties of angiotensin II analogues.
AB  - The present study investigates the importance of the amino acid side chains in
      the octapeptide angiotensin II (Ang II) for binding to the AT2 receptor. A Gly
      scan was performed where each amino acid in Ang II was substituted one-by-one
      with glycine. The resulting set of peptides was tested for affinity to the AT2
      receptor (porcine myometrial membranes). For a comparison, the peptides were also
      tested for affinity to the AT1 receptor (rat liver membranes). Only the
      substitution of Arg2 reduced affinity to the AT2 receptor considerably (92-fold
      when compared with Ang II). For the other Gly-substituted analogues the affinity
      to the AT2 receptor was only moderately affected. To further investigate the role
      of the Arg2 side chain for receptor binding, we synthesized some N-terminally
      modified Ang II analogues. According to these studies a positive charge in the N
      terminal end of angiotensin III [Ang II (2-8)] is not required for high AT2
      receptor affinity but seems to be more important in Ang II. With respect to the
      AT1 receptor, [Gly2]Ang II and [Gly8]Ang II lacked binding affinity (Ki > 10
      microM). Replacement of the Val3 or Ile5 residues with Gly produced only a slight
      decrease in affinity. Interestingly, substitution of Tyr4 or His6, which are
      known to be very important for AT1 receptor binding, resulted in only 48 and 14
      times reduction in affinity, respectively.

PMID- 15485558
TI  - A napin-like polypeptide with translation-inhibitory, trypsin-inhibitory,
      antiproliferative and antibacterial activities from kale seeds.
AB  - A heterodimeric napin-like polypeptide with translation-inhibiting and
      antibacterial activities has been isolated from kale seeds. The purification
      procedure entailed ion-exchange chromatography on dielthylaminoethyl (DEAE)
      cellulose, affinity chromatography on Affi-gel blue gel, ion-exchange
      chromatography by fast protein liquid chromatography (FPLC) on Mono S, and gel
      filtration by FPLC on Superdex 75. The napin-like polypeptide was unadsorbed on
      DEAE-cellulose but adsorbed on Affi-gel blue gel and Mono S. Its 7-kDa large
      subunit differs in N-terminal amino acid sequence from the 4-kDa small subunit.
      The polypeptide inhibited translation in the rabbit reticulocyte lysate system
      with an IC50 of 37.5 nM. This activity was preserved between pH 5 and pH 11, and
      between 10 and 40 degrees C. It fell to a low level at pH 3 and pH 13 and at 70
      degrees C. Antibacterial activity against Bacillus, Megabacterium, and
      Pseudomonas species and antiproliferative activity against leukemia L1210 cells
      were observed. However, the polypeptide did not exert antifungal, ribonuclease,
      or protease activity.

PMID- 15485559
TI  - Comparison of the metabolic and antioxidant effects of diltiazem and vitamin E on
      streptozotocin-diabetic rats.
AB  - In this study, solitary and combined effects of vitamin E and the calcium-channel
      blocker diltiazem were investigated in streptozotocin (STZ)-induced diabetic
      rats. Thirty male Wistar albino rats, weighing approximately 200 g were used.
      Diabetes mellitus was induced by a single intravenous injection of STZ at a dose
      of 65 mg/kg body weight. Five experimental groups were established as STZ
      diabetic, STZ-diabetic + vitamin E, STZ-diabetic + diltiazem and STZ-diabetic +
      vitamin E + diltiazem. Vitamin E was injected intraperitoneally three times a
      week at a dose of 500 mg/kg body weight. Diltiazem was given orally every day at
      a dose of 25 mg/kg body weight. At the end of the study (10 weeks) blood glucose
      levels of diabetic rats, which had received vitamin E and diltiazem, had
      significantly decreased when compared with untreated diabetic rats (P < 0.02).
      Similarly, HbA1c levels had significantly decreased in diabetic rats which had
      received vitamin E (P < 0.05), diltiazem (P < 0.01) and vitamin E + diltiazem (P
      < 0.02) when compared with untreated diabetic rats. Liver glutathione levels of
      diabetic rats, which had received vitamin E (P < 0.01) and vitamin E + diltiazem
      (P < 0.05) had significantly increased when compared with untreated diabetic
      rats. Liver lipid peroxide levels had significantly decreased in diabetic rats,
      which had received vitamin E (P < 0.001) and diltiazem (P < 0.01). With respect
      to their metabolic and antioxidant effects, vitamin E proved superior to
      diltiazem.

PMID- 15485560
TI  - The acyclic period postpartum in automatic and conventional milking.
AB  - The acyclic postpartum period in cows is prolonged due to frequent suckling when
      compared with twice daily milking. In conventional milking systems twice daily
      milking is common, while in automatic milking systems (AMS) three or more
      milkings are performed in early lactation. In this study, the hypothesis was
      tested that an increased milking frequency in AMS causes a delay in resumption of
      ovarian cyclicity postpartum and increases days open in German Fleckvieh cows (n
      = 124). Calvings were equally distributed throughout the 1-year experimental
      period. All cows were housed in one barn. Sixty-three cows were milked in an AMS
      (AC) and 61 cows were twice daily milked in a conventional milking parlour (PC).
      Forty-two AC and 36 PC remained in the herd until conception. After parturition,
      milk samples were analysed for progesterone twice weekly to record the ovarian
      activity until pregnancy was diagnosed. The first and the second ovulation were
      determined by the progesterone profile of each individual cow. The mean milking
      frequency during the first 3 weeks after parturition was higher in AC (3.17 +/-
      0.09 milkings/day) than in PC (milked twice daily). The individual mean milking
      frequency of AC for the first 3 weeks of lactation ranged from 2.0 to 5.9 daily
      milkings. The time span from parturition until the first and second ovulation did
      not differ between AC and PC. However, first ovulation was observed earlier in
      primiparous (23 +/- 1 days) than in multiparous cows (29 +/- 1 days, P < 0.05).
      Within AC no relationship between milking frequency and duration of the acyclic
      period was observed. Days open did not significantly differ between AC and PC and
      between primiparous and multiparous cows. In conclusion, the increased milking
      frequency in AMS did neither cause a delay in resumption of ovarian cyclicity
      postpartum nor did it increase days open.

PMID- 15485561
TI  - Tamoxifen decreases level of immunoglobulins in blood of the hen (Gallus
      domesticus) without alteration in non-immunoglobular fractions of plasma
      proteins.
AB  - The effect of tamoxifen (TMX), an anti-estrogen compound, on immunoglobulins (Ig)
      level in blood plasma of laying hens was investigated. TMX (4 mg/hen/day) was
      given per os for seven consecutive days; control hens received placebo. Blood
      samples were collected from the wing vein every day before TMX treatment, and
      plasma Ig levels were measured by means of Rlebodzinski's test. TMX significantly
      decreased plasma Ig levels, maximally by 51% on day 2 of the experiment. The
      observed reduction in Ig level was accompanied by the significant, 37% decrease
      in the ratio of Ig/total protein (Tp). From the third day of TMX treatment, level
      of Ig and the ratio of Ig/Tp gradually increased and on the day 5 of the
      experiment no difference between control and experimental group was found. In non
      immunoglobular (Tp-Ig) fractions of plasma proteins no significant alterations
      after TMX treatment were observed. Therefore, treatment of laying hens with TMX
      transiently decreased plasma Ig levels. Most likely the effect of TMX is
      associated with the antagonistic properties of TMX toward estrogen receptors. On
      the contrary, the transient decrease in plasma Ig levels of TMX-treated hens
      followed by the gradual increase suggests adaptation of the immunological system
      to treatment with the anti-estrogen preparation.

PMID- 15485562
TI  - Cerebellar focal granulomatous meningoencephalitis in a dog: clinical findings
      and MR imaging.
AB  - The authors encountered a dachshund dog, presenting vestibular disorder. On
      magnetic resonance (MR) imaging, a mass showing isointensity on the T1- and T2
      weighted images and enhanced by contrast medium, was observed in the right
      cerebellum. In addition, the periphery of the mass showed isointensity on the T1
      weighted image and hyperintensity on the T2-weighted image, suggesting sever
      oedema. Although the dog underwent surgery, it died. The mass was diagnosed
      pathologically as a granulomatous meningoencephalitis.

PMID- 15485563
TI  - Meningoencephalomyelitis caused by Neospora caninum in a juvenile fallow deer
      (Dama dama).
AB  - Neosporosis, caused by the protozoan parasite Neospora caninum, is a serious
      cause of bovine abortion, stillbirth and perinatal death. This paper reports a
      clinical neosporosis in a 3-week-old fallow deer (Dama dama). The fawn was full
      term and appeared normal at birth. Histological lesions consisted of a multifocal
      necrotizing and granulomatous meningoencephalomyelitis, with intralesional
      protozoal cysts. Positive immunohistochemical staining and characteristic PCR
      products confirmed the diagnosis of N. caninum infection.

PMID- 15485564
TI  - The use of a circular external skeletal fixation device for the management of
      long bone osteotomies in large ruminants: an experimental study.
AB  - The study was undertaken to evaluate the feasibility of a simple, inexpensive
      model of circular external fixator (CEF) for use in large ruminants. A simple
      model of CEF frames consisting of four full rings (13-19 cm diameter, 4 cm wide
      and 4 mm thick with 18-24 holes) connected by threaded rods (8 mm diameter, 10-15
      cm long) and nuts was developed using mild (low carbon) steel and were nickel
      plated. In the first phase of the study, three male cow calves were utilized to
      study the feasibility of application of the fixators in the metatarsus, tibia and
      radius, in reference of adaptation and tolerance by animals. In the second phase,
      the fixators were tested in osteotomized bones. Six bull calves of 1.5-2 years of
      age weighing about 200-250 kg were utilized for this purpose. After preparing the
      area for aseptic surgery, under xylazine (at 0.1 mg/kg, i.m.)-ketamine (i.v. till
      effect) general anaesthesia, the test bone (metatarsus, radius and tibia in two
      animals each) was approached through the medial surface and an osteotomy was
      created with a saw and chisel at the mid-diaphysis. The pre-constructed 4-ring
      CEF was mounted on the limb around the test bone in such a way that it formed a
      cylinder with the axis of the limb at the centre. Each ring was then fixed to the
      bone with a pair of beaded wires (316 SS) of 3.5 mm diameter. During the post
      operative period, the animals were observed for any change in behaviour,
      tolerance of the fixators, the weight bearing on the test limb, the status of the
      fixator, and the level of reduction of the osteotomy, alignment and healing at
      different intervals. The fixation of CEF was easier in the metatarsus and radius
      than in the tibia. The inner ring diameters found adequate for metatarsus, radius
      and tibia were 13-15 cm, 15-17 cm and 17-19 cm, respectively. The fixators
      applied to different bones were well-tolerated, and the animals could lay down,
      stand and walk freely with the fixator without any problems. All the animals
      showed good weight bearing in the immediate post-operative period. Weight
      bearing, however, slightly reduced in the inflammatory period and showed
      improvement after about 4 weeks. Wire tract infection was seen in all the
      animals, which was more on proximal wire tracts on lateral aspect of limbs.
      Circular fixators were well-tolerated by all the animals, and there was no
      breaking/bending of connecting rods, slotted bolts or the rings at any stage of
      observation. Slight bowing of some wires was noticed in cases of tibia and radius
      (in phase II) and bending of some wires was noticed from first week in two
      animals one each in radius and tibia. Bone fragments were well maintained until
      healing occurred (appearance of bridging periosteal callus) at 60-70 days. The
      functional results were good in all but one case of tibia, where a mal-union was
      recorded. From this study, it can be concluded that CEF are well-tolerated by
      large ruminants and can be used to treat long bone fractures. The fixator
      assembly using mild steel is sufficiently strong to maintain fracture fixation
      and is inexpensive. The simple design of the CEF appears to be sufficient to
      treat simple diaphyseal fractures of the metatarsus and radius. Improvement in
      the technique of fixation and design-like coupling of linear and circular fixator
      components into hybrid constructs may help to provide greater rigidity in
      treating tibial and open long bone fractures.

PMID- 15485565
TI  - Survival of dairy cows after surgery to correct abomasal displacement: 1.
      Clinical and laboratory parameters and overall survival.
AB  - The objective of this study was to compare the clinical and laboratory
      consequences of left and right displacement of the abomasum (LDA and RDA), short-
      and long-term survival after surgery and the findings in cows, that could not be
      cured by omentopexy. Data from 564 cases of displaced abomasum (466 LDA, 98 RDA)
      were analysed retrospectively. Clinical and laboratory findings were compared
      between the two manifestations of DA. Survival was assessed after 10 days and
      after 15 months. Necropsy was carried out on cows that died or were killed. On
      arrival at the clinic, left displacement of the abomasum (LDA) cows had been
      recognized as diseased for longer. LDA occurred earlier in lactation, and more
      cows with right displacement of the abomasum (RDA) were pregnant. Overall
      clinical symptoms were more severe in RDA than in LDA cows. Heart rate was
      higher, body temperature was lower, inanition, abnormal faeces and ruminal stasis
      were more frequent in RDA cows. Leucocyte counts were higher, and potassium and
      chloride levels were lower in RDA cows. Acetonuria was more frequent in LDA cows.
      More LDA than RDA cows were released from the clinic as cured (82.0% versus
      74.5%). However, survival after the early post-surgical period was similar for
      RDA and LDA cows. At necropsy, diseases of the gastrointestinal system were the
      predominant finding in RDA cows, while in LDA cows, diseases of the liver and
      other concurrent diseases were more important.

PMID- 15485566
TI  - Survival of dairy cows after surgery to correct abomasal displacement: 2.
      Association of clinical and laboratory parameters with survival in cows with left
      abomasal displacement.
AB  - This study examines the association of pre-surgical clinical parameters in cows
      with left displacement of the abomasum (LDA) with the probability of cure. Data
      from 466 cases of LDA in which omentopexy was performed were analysed. Cows were
      classified in three categories according to the outcome of treatment. Cows in the
      first category were cured, i.e. sent back to the farm for further milk
      production. Cows in the second category were sent for slaughter because of an
      unfavourable prognosis concerning productivity. Cows in the third category either
      died or were salvaged because of poor prognosis concerning survival. Factors were
      examined for their possible influence on the outcome of treatment by comparing
      the values of successfully treated cows to those cows that either died or had to
      be sent for slaughter. Factors that were associated with a favourable prognosis
      were a short duration of disease, an undisturbed general condition, good
      appetite, normal faeces, a higher body weight, lower haematocrit, haemoglobin and
      erythrocyte counts, lower urea, AST and bilirubin, and higher sodium, potassium
      and chloride concentrations compared with cows with an unfavourable prognosis.
      Haemoconcentration was associated with higher AST, bilirubin and urea and with
      low sodium, potassium and chloride. Acetonuria was associated with increased AST
      and bilirubin and low urea. Low sodium and potassium concentrations were
      associated with an impaired general condition. It is concluded that a thorough
      clinical examination with special emphasis on general condition, liver function
      and dehydration status is of great importance in determining the prognosis of
      abdominal surgery in cows with LDA.

PMID- 15485567
TI  - Field evaluation of the effect of a probiotic-containing Bacillus licheniformis
      and Bacillus subtilis spores on the health status, performance, and carcass
      quality of grower and finisher pigs.
AB  - The aim of the study was to assess the efficacy of BioPlus 2B, a probiotic
      containing Bacillus licheniformis and B. subtilis spores, on the health status
      and productivity of pigs, during weaning, growing and finishing stages of growth.
      On a commercial farrow-to-finish farm, five experimental groups were formed, each
      of 54 weaned piglets. The pigs of the first group (double controls) received
      normal feed with no probiotic and the pigs of the second group (untreated
      controls) received BioPlus 2B only during the weaning stage. The pigs of the
      third, the fourth and the fifth group received the same as the second group feed
      but, at the growing and at a part of the finishing stages, supplemented with
      three different doses of Bioplus 2B, a low, medium and high dose, respectively.
      The results have shown that, compared with the double controls, BioPlus 2B
      treated pigs had a lower morbidity and mortality during the whole trial period,
      compared with the double controls (range from 9.26 to 14.81% versus 25.93% and
      from 0.00 to 3.70% versus 11.1%, respectively), as a result of the lower
      incidence of post-weaning diarrhoea due mainly to Escherichia coli. Weight gain,
      feed conversion ratio and carcass quality of the BioPlus 2B-treated pigs were
      significantly improved compared with the double controls, whilst the beneficial
      effects of the probiotic were more pronounced when the medium and high doses were
      used.

PMID- 15485568
TI  - Dual-energy X-ray absorptiometry of birds: an examination of excised skeletal
      specimens.
AB  - The ability of dual-energy X-ray absorptiometry (DXA) to measure bone mineral
      content and density of bird bones has received little attention. This paper
      represents the first comprehensive study of the methods, precision, and
      reproducibility of DXA (GE-Lunar DPX-L) for the uniquely shaped, thin and
      pneumatic bones of birds. Skeletal elements and portions represented by 26
      regions of interest (ROIs) are presented and evaluated for the gallinaceous bird
      species, wild turkey (Meleagris gallopavo), ruffed grouse (Bonasa umbellus) and
      bobwhite quail (Colinus virginianus). Using Lunar small animal software and the
      methods described in this paper, photodensitometry of bird bones is possible and
      opens new opportunities for using birds in clinical models in veterinarian
      science, osteoporosis studies, space biology, and even archaeological and
      paleontological research.

PMID- 15485570
TI  - ISPOR 7th Annual European Congress. 24-26 October, 2004, Hamburg, Germany.
      Abstracts.

PMID- 15485571
TI  - Traumatic deep vein thrombosis in a soccer player: A case study.
AB  - A 42 year-old male former semi-professional soccer player sustained a right lower
      extremity popliteal contusion during a soccer game. He was clinically diagnosed
      with a possible traumatic deep vein thrombosis (DVT), and sent for confirmatory
      tests. A duplex doppler ultrasound was positive for DVT, and the patient was
      admitted to hospital for anticoagulation (unfractionated heparin, warfarin). Upon
      discharge from hospital the patient continued oral warfarin anticoagulation (six
      months), and the use of compression stockings (nine months). He followed up with
      his family doctor at regular intervals for serial coagulation measurements, and
      ultrasound examinations. The patient's only identified major thrombotic risk
      factor was the traumatic injury. One year after the initial deep vein thrombosis
      (DVT) the patient returned to contact sport, however he continued to have
      intermittent symptoms of right lower leg pain and right knee effusion.Athletes
      can develop vascular injuries in a variety of contact and non-contact sports.
      Trauma is one of the most common causes of lower extremity deep vein thrombosis
      (DVT), however athletic injuries involving lower extremity traumatic DVT are
      seldom reported. This diagnosis and the associated risk factors must be
      considered during the initial physical examination. The primary method of
      radiological diagnosis of lower extremity DVT is a complete bilateral duplex
      sonography, which can be augmented by other methods such as evidence-based risk
      factor analysis. Antithrombotic medication is the current standard of treatment
      for DVT. Acute thrombolytic treatment has demonstrated an improved therapeutic
      efficacy, and a decrease in post-DVT symptoms.There is a lack of scientific
      literature concerning the return to sport protocol following a DVT event.
      Athletic individuals who desire to return to sport after a DVT need to be fully
      informed about their treatment and risk of reoccurrence, so that appropriate
      decisions can be made.

PMID- 15485572
TI  - Improved hit criteria for DNA local alignment.
AB  - BACKGROUND: The hit criterion is a key component of heuristic local alignment
      algorithms. It specifies a class of patterns assumed to witness a potential
      similarity, and this choice is decisive for the selectivity and sensitivity of
      the whole method. RESULTS: In this paper, we propose two ways to improve the hit
      criterion. First, we define the group criterion combining the advantages of the
      single-seed and double-seed approaches used in existing algorithms. Second, we
      introduce transition-constrained seeds that extend spaced seeds by the
      possibility of distinguishing transition and transversion mismatches. We provide
      analytical data as well as experimental results, obtained with the YASS software,
      supporting both improvements. CONCLUSIONS: Proposed algorithmic ideas allow to
      obtain a significant gain in sensitivity of similarity search without increase in
      execution time. The method has been implemented in YASS software available at
      http://www.loria.fr/projects/YASS/.

PMID- 15485573
TI  - The effect of chemotherapy combined with recombination mutant human tumor
      necrosis factor on advanced cancer.
AB  - BACKGROUND: Past studies suggested that tumor necrosis factor (TNF) assisted anti
      tumor treatment and intensified the sensitivity of chemotherapy. However its
      clinical application has been curbed because of its low purity, high dosage, and
      strong toxicity. This research, through perspective random clinical control
      experiment, observed the therapeutic effect of the treatment of late malignant
      tumor through the injection of recombinant mutant human tumor necrosis factor
      (rmhTNF) combined with general chemotherapy and its adverse reactions. METHODS:
      105 patients with advanced malignant tumor were randomly divided into trial
      group, 69 patients, and control group, 36 patients. Injection of rmhTNF 4 x
      106u/m2 was given to the trial group, from the 1st to 7th days, the 11th to 17th
      days combined with chemotherapy course. The chemotherapy plan was as follows: CAP
      for patients with the NSCLC; FAM for patients with gastric cancer; FC for
      patients with colorectal cancer. One treatment cycle lasted for 21 days and two
      cycles were scheduled. The control group was given only the same chemotherapy as
      the trial group. RESULTS: In the trial group there was 1 CR case and 12 PR cases,
      and the response rate is 13/69 (18.84%); in the control group 1 PR case, the
      response rate 1/36 (2.78%). The response rate of the trial group was
      significantly higher than that of the control group (P = 0.022). The response
      rate for NSCLC in the trial group was 8/17 (47.06%), and 1/6 (16.67%) in the
      control group. The response rates for gastric cancer and colorectal cancer in the
      trial groups also were higher than those of the control groups. After the
      treatment the KPS is 89.00 +/- 9.92 in the trial group, and 84.17 +/- 8.84 in the
      control group, with a significant difference between the two groups (P = 0.028).
      The adverse reactions of rmhTNF injection included: pain in the injection area,
      chill, hardening and swelling and redness in the injection area, fever, ostealgia
      and myosalgia, and cold-like symptoms. All these adverse reactions were mild and
      bearable. CONCLUSIONS: The administration of rmhTNF injection in combination with
      general chemotherapy is an effective and secure means in treating advanced
      malignant tumor.

PMID- 15485574
TI  - BIOKID: randomized controlled trial comparing bicarbonate and lactate buffer in
      biocompatible peritoneal dialysis solutions in children [ISRCTN81137991].
AB  - BACKGROUND: Peritoneal dialysis (PD) is the preferred dialysis modality in
      children. Its major drawback is the limited technique survival due to infections
      and progressive ultrafiltration failure. Conventional PD solutions exert marked
      acute and chronic toxicity to local tissues. Prolonged exposure is associated
      with severe histopathological alterations including vasculopathy,
      neoangiogenesis, submesothelial fibrosis and a gradual loss of the mesothelial
      cell layer. Recently, more biocompatible PD solutions containing reduced amounts
      of toxic glucose degradation products (GDPs) and buffered at neutral pH have been
      introduced into clinical practice. These solutions contain lactate, bicarbonate
      or a combination of both as buffer substance. Increasing evidence from clinical
      trials in adults and children suggests that the new PD fluids may allow for
      better long-term preservation of peritoneal morphology and function. However, the
      relative importance of the buffer in neutral-pH, low-GDP fluids is still unclear.
      In vitro, lactate is cytotoxic and vasoactive at the concentrations used in PD
      fluids. The BIOKID trial is designed to clarify the clinical significance of the
      buffer choice in biocompatible PD fluids. METHODS/DESIGN: The objective of the
      study is to test the hypothesis that bicarbonate based PD solutions may allow for
      a better preservation of peritoneal transport characteristics in children than
      solutions containing lactate buffer. Secondary objectives are to assess any
      impact of the buffer system on acid-base status, peritoneal tissue integrity and
      the incidence and severity of peritonitis. After a run-in period of 2 months
      during which a targeted cohort of 60 patients is treated with a conventional,
      lactate buffered, acidic, GDP containing PD fluid, patients will be stratified
      according to residual renal function and type of phosphate binding medication and
      randomized to receive either the lactate-containing Balance solution or the
      bicarbonate-buffered Bicavera solution for a period of 10 months. Patients will
      be monitored by monthly physical and laboratory examinations. Peritoneal
      equilibration tests, 24-h dialysate and urine collections will be performed 4
      times. Peritoneal biopsies will be obtained on occasion of intraabdominal
      surgery. Changes in small solute transport rates, markers of peritoneal tissue
      turnover in the effluent, acid-base status and peritonitis rates and severity
      will be analyzed.

PMID- 15485575
TI  - Road-traffic pollution and asthma - using modelled exposure assessment for
      routine public health surveillance.
AB  - Asthma is a common disease and appears to be increasing in prevalence. There is
      evidence linking air pollution, including that from road-traffic, with asthma.
      Road traffic is also on the increase. Routine surveillance of the impact of road
      traffic pollution on asthma, and other diseases, would be useful in informing
      local and national government policy in terms of managing the environmental
      health risk.Several methods for exposure assessment have been used in studies
      examining the association between asthma and road traffic pollution. These
      include comparing asthma prevalence in areas designated as high and low pollution
      areas, using distance from main roads as a proxy for exposure to road traffic
      pollution, using traffic counts to estimate exposure, using vehicular miles
      travelled and using modelling techniques. Although there are limitations to all
      these methods, the modelling approach has the advantage of incorporating several
      variables and may be used for prospective health impact assessment.The modelling
      approach is already in routine use in the United Kingdom in support of the
      government's strategy for air quality management. Combining information from such
      models with routinely collected health data would form the basis of a routine
      public health surveillance system. Such a system would facilitate prospective
      health impact assessment, enabling policy decisions concerned with road-traffic
      to be made with knowledge of the potential implications. It would also allow
      systematic monitoring of the health impacts when the policy decisions and plans
      have been implemented.

PMID- 15485577
TI  - Effects of recombinant adenovirus-mediated expression of IL-2 and IL-12 in human
      B lymphoma cells on co-cultured PBMC.
AB  - BACKGROUND: Modulation of the immune system by genetically modified lymphoma cell
      vaccines is of potential therapeutic value in the treatment of B cell lymphoma.
      However, the anti-tumor effect of any single immunogene transfer has so far been
      limited. Combination treatment of recombinant IL-2 and IL-12 has been reported to
      be synergistic for inducing anti-tumor responses in solid tumors but the
      potential of IL-2/IL-12 gene modified B cell lymphoma cells has not been explored
      yet. METHODS: Using three different human B cell lymphoma cell lines and primary
      samples from patients with B cell neoplasms, expression levels of the coxsackie B
      adenovirus receptor (CAR) and alpha (v) integrins were analyzed by fluorescence
      activated cell sorter (FACS). Adenoviral transduction efficiencies were
      determined by GFP expression analysis and IL-2 and IL-12 cytokine production was
      quantified by enzyme-linked immunosorbent (ELISA) assays. Proliferative
      activities of peripheral blood mononuclear cells (PBMC) stimulated with either
      cytokine derived from supernatants of transduced lymphoma cells were measured by
      cell proliferation (MTT) assays. An EuTDA cytotoxicity assay was used to compare
      cytotoxic activities of IL-2 and/or IL-12 stimulated PBMC against unmodified
      lymphoma cells. RESULTS: We found that B cell lymphoma cell lines could be
      transduced with much higher efficiency than primary tumor samples, which appeared
      to correlate with the expression of CAR. Adenoviral-expressed IL-2 and IL-12
      similarly led to dose-dependent increases in proliferation rates of PBMC obtained
      from healthy donors. IL-2 and/or IL-12 transduced lymphoma cells were co-cultured
      with PBMC, which were assayed for their cytolytic activity against unmodified
      lymphoma cells. We found that IL-2 stimulated PBMC elicited a significant anti
      tumor effect but not the combined effect of IL-2/IL-12 or IL-12 alone.
      CONCLUSION: This study demonstrates that the generation of recombinant adenovirus
      modified lymphoma cell vaccines based on lymphoma cell lines expressing IL-2 and
      IL-12 cytokine genes is technically feasible, induces increases in proliferation
      rates and cytotoxic activity of co-cultured PBMC, and warrants further
      development for the treatment of lymphoma patients in the future.

PMID- 15485576
TI  - Effect of the G-308A polymorphism of the tumor necrosis factor (TNF)-alpha gene
      promoter site on plasma levels of TNF-alpha and C-reactive protein in smokers: a
      cross-sectional study.
AB  - BACKGROUND: Plasma levels of tumor necrosis factor (TNF)-alpha and of C-reactive
      protein (CRP) are elevated in smokers. Previous studies failed to show an
      association between the G-308A polymorphism in the promoter region of the TNF
      alpha gene and coronary artery disease (CAD). We investigated whether smoking
      would interact with the TNF-alpha G-308A polymorphism in determining plasma
      levels of TNF-alpha and CRP. METHODS: Study participants with a complete data set
      in terms of smoking and the TNF-alpha G-308A polymorphism were 300 middle-aged
      male and female industrial employees. After excluding 24 irregular smokers,
      analyses were performed on 198 "non-smokers" (life-long non-smokers or subjects
      who quit smoking >6 months ago) as compared to 78 "regular smokers" (subjects
      currently smoking >3 cigarettes/day). All subjects had a fasting morning blood
      draw to measure plasma levels of TNF-alpha and CRP by high-sensitive enzyme
      linked immunosorbent assays. RESULTS: The cardiovascular risk factor adjusted
      analysis regressing log-transformed CRP levels against smoking status, genotype,
      and smoking-status-genotype interaction revealed a significant main effect for
      smoking status (F1,250 = 5.67, p = .018) but not for genotype (F1,250 = 0.33, p =
      .57). The interaction-term between genotype and smoking status was not
      significant (F1,250 = 0.09, p = .76). The fully adjusted model with plasma TNF
      alpha failed to show significant main effects for smoking and genotype, as well
      as for the smoking-status-genotype interaction. CONCLUSIONS: The findings suggest
      that the TNF-alpha G-308A polymorphism does not mediate the effect of smoking on
      plasma CRP levels. It remains to be seen whether other genetic polymorphisms
      along the inflammatory pathway may modulate vascular risk in smokers.

PMID- 15485578
TI  - A high prevalence of cumulative trauma disorders in Iranian instrumentalists.
AB  - BACKGROUND: Cumulative trauma disorders (CTDs) are common in musicians and their
      prevalence has been the subject of a number of studies in most western countries.
      Such studies are scarce in developing countries despite the possibility that CTDs
      may have a different prevalence in these countries, especially when considering
      traditional musical instruments and different methods of playing. Although not
      formally studied before, according to our experience the prevalence of CTDs
      seemed to be high among Iranian instrumentalists. We proposed this study to
      determine the prevalence of CTDs in amateur music students playing one of the two
      traditional Iranian instruments: Daf and Setar. METHODS: In a prospective cross
      sectional study, we interviewed and examined the students of three music training
      centers in Iran. Seventy eight instrumentalists, who were playing Daf or Setar
      and twelve students who had not started playing yet were regarded as case and
      control groups respectively. Some of them also underwent electrodiagnostic
      studies. RESULTS: Forty-seven percent (17 of 36) of the Setar players and 57% (24
      of 42) of the Daf players and fifty-three percent (41 of 78) of the
      instrumentalists as a whole had CTDs. None of them had carpal tunnel syndrome.
      CONCLUSIONS: Our study revealed that the prevalence of CTDs in Iranian
      instrumentalists was unusually high. In addition to age, other variables may be
      contributory. This needs to be further studied.

PMID- 15485579
TI  - Funding free and universal access to Journal of Neuroinflammation.
AB  - Journal of Neuroinflammation is an Open Access, online journal published by
      BioMed Central. Open Access publishing provides instant and universal
      availability of published work to any potential reader, worldwide, completely
      free of subscriptions, passwords, and charges. Further, authors retain copyright
      for their work, facilitating its dissemination. Open Access publishing is made
      possible by article-processing charges assessed "on the front end" to authors,
      their institutions, or their funding agencies. Beginning November 1, 2004, the
      Journal of Neuroinflammation will introduce article-processing charges of around
      US$525 for accepted articles. This charge will be waived for authors from
      institutions that are BioMed Central members, and in additional cases for reasons
      of genuine financial hardship. These article-processing charges pay for an
      electronic submission process that facilitates efficient and thorough peer
      review, for publication costs involved in providing the article freely and
      universally accessible in various formats online, and for the processes required
      for the article's inclusion in PubMed and its archiving in PubMed Central, e
      Depot, Potsdam and INIST. There is no remuneration of any kind provided to the
      Editors-in-Chief, to any members of the Editorial Board, or to peer reviewers;
      all of whose work is entirely voluntary. Our article-processing charge is less
      than charges frequently levied by traditional journals: the Journal of
      Neuroinflammation does not levy any additional page or color charges on top of
      this fee, and there are no reprint costs as publication-quality pdf files are
      provided, free, for distribution in lieu of reprints. Our article-processing
      charge will enable full, immediate, and continued Open Access for all work
      published in Journal of Neuroinflammation. The benefits from such Open Access
      will accrue to readers, through unrestricted access; to authors, through the
      widest possible dissemination of their work; and to science and society in
      general, through facilitation of information availability and scientific
      advancement.

PMID- 15485580
TI  - Punica granatum (Pomegranate) juice provides an HIV-1 entry inhibitor and
      candidate topical microbicide.
AB  - BACKGROUND: For approximately 24 years the AIDS pandemic has claimed
      approximately 30 million lives, causing approximately 14,000 new HIV-1 infections
      daily worldwide in 2003. About 80% of infections occur by heterosexual
      transmission. In the absence of vaccines, topical microbicides, expected to block
      virus transmission, offer hope for controlling the pandemic. Antiretroviral
      chemotherapeutics have decreased AIDS mortality in industrialized countries, but
      only minimally in developing countries. To prevent an analogous dichotomy,
      microbicides should be: acceptable; accessible; affordable; and accelerative in
      transition from development to marketing. Already marketed pharmaceutical
      excipients or foods, with established safety records and adequate anti-HIV-1
      activity, may provide this option. METHODS: Fruit juices were screened for
      inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors. The
      best juice was tested for inhibition of: (1) infection by HIV-1 BaL, utilizing
      CCR5 as the cellular coreceptor; and (2) binding of gp120 IIIB and gp120 BaL,
      respectively, to CXCR4 and CCR5. To remove most colored juice components, the
      adsorption of the effective ingredient(s) to dispersible excipients and other
      foods was investigated. A selected complex was assayed for inhibition of
      infection by primary HIV-1 isolates. RESULTS: HIV-1 entry inhibitors from
      pomegranate juice adsorb onto corn starch. The resulting complex blocks virus
      binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to
      G and group O. CONCLUSION: These results suggest the possibility of producing an
      anti-HIV-1 microbicide from inexpensive, widely available sources, whose safety
      has been established throughout centuries, provided that its quality is
      adequately standardized and monitored.

PMID- 15485581
TI  - Pimecrolimus 1% cream for anogenital lichen sclerosus in childhood.
AB  - BACKGROUND: Lichen sclerosus is a chronic inflammatory disease with a
      predilection of the anogenital region. Because of the potential side effects of
      repeated local application of potent glucocorticosteroids, equally-effective,
      safer therapeutic options are required, especially in the treatment of children.
      CASE PRESENTATIONS: We report on the efficacy of twice-daily application of
      pimecrolimus 1% cream in four prepubertal girls (range of age: 4 to 9 years) who
      suffered from anogenital lichen sclerosus. After three to four-month treatment,
      all patients had almost complete clinical remission including relief from itch,
      pain and inflammation. Only minor improvement was observed for the white
      sclerotic lesions. No significant side effects have been observed. CONCLUSIONS:
      Topical pimecrolimus appears to be an effective and safe treatment for children
      with anogenital lichen sclerosus. The clinical benefits observed in the four
      patient presented particularly include relief of pruritus, pain and inflammation.
      Vehicle-controlled studies on a larger number of patients are now warranted to
      substantiate our promising findings, and to investigate long-term efficacy and
      safety of topical pimecrolimus in anogenital lichen sclerosus.

PMID- 15485582
TI  - Patterns of use, dosing, and economic impact of biologic agent use in patients
      with rheumatoid arthritis: a retrospective cohort study.
AB  - BACKGROUND: Variability in dosing and costs of biologics among patients with
      rheumatoid arthritis (RA) is of interest to healthcare descision-makers. We
      examined dosing and costs among RA patients newly treated with infliximab or
      etanercept under conditions of typical clinical practice. METHODS: Integrated
      pharmacy and medical claims data were obtained from 61 U.S. health plans. RA
      patients newly treated with infliximab or etanercept between July 1999-June 2002
      were selected. A maintenance number of infliximab vials was determined after the
      "loading period" (2-3 infusions); those with >or= 2 occurrences of an increase in
      vials or an interval between infusions of <49 days were considered to have had
      escalated. For etanercept patients, escalation was based on >or= 2 instances of
      increased average daily dose. Multiple logistic regression analyses were
      conducted to assess variables associated with dose escalation. RA-related costs
      at one year post-initiation also were examined; comparisons were made using
      generalized linear models. RESULTS: A total of 1,548 patients were identified (n
      = 598 and 950 for infliximab and etanercept respectively). Infliximab recipients
      were somewhat older (50.5 vs. 46.6 years for etanercept). Nearly 60% of
      infliximab patients increased their dose at one year, compared to 18% for
      etanercept. Infliximab patients who escalated dose incurred a 25% increase in
      mean one-year costs (20,915 dollars vs. 16,713 dollars for no increase; p <
      0.0001). Costs among etanercept patients did not substantially differ based on
      dose escalation (14,482 dollars vs. 13,866 dollars respectively). CONCLUSIONS:
      Infliximab is associated with higher rates of dose escalation relative to
      etanercept, which contributes to substantially higher one-year medical costs.

PMID- 15485583
TI  - Use of polyethyleneimine polymer in cell culture as attachment factor and
      lipofection enhancer.
AB  - BACKGROUND: Several cell lines and primary cultures benefit from the use of
      positively charged extracellular matrix proteins or polymers that enhance their
      ability to attach to culture plates. Polyethyleneimine is a positively charged
      polymer that has gained recent attention as a transfection reagent. A less known
      use of this cationic polymer as an attachment factor was explored with several
      cell lines. RESULTS: Polyethyleneimine compared favorably to traditional
      attachment factors such as collagen and polylysine. PC-12 and HEK-293 cells
      plated on dishes coated with polyethyleneimine showed a homogeneous distribution
      of cells in the plate, demonstrating strong cell adhesion that survived washing
      procedures. The polymer could also be used to enhance the adherence and allow
      axonal outgrowth from zebrafish retinal explants. The effects of this coating
      agent on the transfection of loosely attaching cell lines were studied. Pre
      coating with polyethyleneimine had the effect of enhancing the transfection yield
      in procedures using lipofection reagents. CONCLUSION: Polyethyleneimine is an
      effective attachment factor for weakly anchoring cell lines and primary cells.
      Its use in lipofection protocols makes the procedures more reliable and increases
      the yield of expressed products with commonly used cell lines such as PC-12 and
      HEK-293 cells.

PMID- 15485584
TI  - Who's driving the centromere?
AB  - Centromere function is remarkably conserved between species, yet the satellite
      sequences that make up centromeric DNA are highly divergent. Proteins that bind
      these sequences appear to be evolving under positive selection, supporting a
      model wherein the interplay between centromeric repeats and the proteins that
      bind them creates an opportunity for an intriguing phenomenon known as centromere
      based meiotic drive.

PMID- 15485585
TI  - Adverse effect of fish oils in patients with angina?

PMID- 15485586
TI  - Whole grain intake and cardiovascular disease: a review.
AB  - Prospective epidemiologic and feeding studies find possible health benefits of
      whole cereal grain foods (which include the bran, germ, and endosperm in their
      naturally occurring proportions), especially for prevention of atherosclerotic
      cardiovascular diseases and type 2 diabetes. We review 17 articles that
      consistently found a 20% to 40% reduction in long-term risk of these diseases
      comparing habitual consumers of whole grains to those who rarely eat these foods.
      Another 12 studies found a similar risk reduction according to amount of cereal
      fiber consumed. Feeding studies show improvements in risk factors for these
      diseases when whole grain foods are consumed. Some authors have tried to explain
      the reduced risk by invoking cereal fiber, with no attention to nonfiber
      constituents. We interpret the data as supportive of a synergy of the whole grain
      constituents, including fiber as only one such constituent.

PMID- 15485587
TI  - Inflammation, insulin resistance, and obesity.
AB  - Obesity, in particular visceral obesity, has strong associations with
      cardiovascular disease and is related to many factors that are constituents of
      the metabolic syndrome. Increasing evidence suggests that features of the
      metabolic syndrome, including visceral obesity, are associated with a low-grade
      inflammatory state. Indeed, visceral fat is a source of several molecules, such
      as leptin, adiponectin, tumor necrosis factor-alpha, and interleukin 6, that are
      collectively called adipokines. All of them may induce a proinflammatory state
      and oxidative damage, leading to initiation and progression of atherosclerosis.
      Reduced-energy diets might represent an effective and healthful approach for long
      term weight loss in patients with metabolic syndrome by reducing the underlying
      inflammatory condition.

PMID- 15485588
TI  - Diet, fatty acids, and regulation of genes important for heart disease.
AB  - Diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), such as alpha
      linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid, are associated
      with decreased incidence and severity of coronary heart disease. Similarly,
      conjugated linoleic acids (CLAs), which are found in meat and dairy products,
      have beneficial effects against atherosclerosis, diabetes, and obesity. The
      effects of n3-PUFAs and CLAs are in contrast to fatty acids with virtually
      identical structures, such as linoleic acid and arachidonic acid (ie, n-6 PUFAs).
      This article discusses the possibility that cognate receptors exist for fatty
      acids or their metabolites that are able to regulate gene expression and
      coordinately affect metabolic or signaling pathways associated with coronary
      heart disease. Three nuclear receptors are emphasized as fatty acid receptors
      that respond to dietary and endogenous ligands: peroxisome proliferator activated
      receptors, retinoid X receptors, and liver X receptors.

PMID- 15485589
TI  - Omega-6 fatty acids and coronary artery disease: the pros and cons.
AB  - Polyunsaturated fatty acids have long been recommended as a beneficial substitute
      for atherogenic saturated fat. The connection between dietary lipids and blood
      cholesterol is still under debate, as is the connection between dietary fat and
      coronary artery disease. Thus, the lipid hypothesis is still a hypothesis. The
      major dietary polyunsaturated fatty acid, linoleic acid of the omega-6 family,
      has several properties that render it hyperinsulinemic and atherogenic. The
      potential benefits of linoleic acid intake regarding coronary artery disease, and
      its possible harms, are discussed.

PMID- 15485590
TI  - Are omega-3 fatty acids the most important nutritional modulators of coronary
      heart disease risk?
AB  - With each passing year, the evidence linking an increased risk for coronary heart
      disease (CHD) death with a chronic dietary deficiency in long-chain omega-3 (n-3)
      fatty acids (FAs) grows stronger. Recently, a federally mandated evidence-based
      review in the United States concluded that n-3 FAs, especially eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA), have clear cardioprotective effects,
      and national and international expert panels and health organizations have begun
      to call for increased EPA and DHA intakes. Consumption of between 450 and 1000
      mg/d is recommended for those without and with known CHD, respectively. Based on
      animal and isolated cell studies, these FAs were presumed to have antiarrhythmic
      effects. The first direct evidence for this in humans was recently published, as
      were new data linking low n-3 FA intakes with risk for developing atrial
      fibrillation. The strength of the n-3 story has now led to a proposal that blood
      levels of EPA plus DHA be considered a new, modifiable, and clinically relevant
      risk factor for death from CHD.

PMID- 15485592
TI  - Omega-3 fatty acids and inflammation.
AB  - Dietary omega-3 (n-3) fatty acids have a variety of anti-inflammatory and immune
      modulating effects that may be of relevance to atherosclerosis and its clinical
      manifestations of myocardial infarction, sudden death, and stroke. The n-3 fatty
      acids that appear to be most potent in this respect are the long-chain
      polyunsaturates derived from marine oils, namely eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), and this review is restricted to these substances. A
      variety of biologic effects of EPA and DHA have been demonstrated from feeding
      studies with fish or fish oil supplements in humans and animals. These include
      effects on triglycerides, high-density lipoprotein cholesterol, platelet
      function, endothelial and vascular function, blood pressure, cardiac
      excitability, measures of oxidative stress, pro- and anti-inflammatory cytokines,
      and immune function. Epidemiologic studies provide evidence for a beneficial
      effect of n-3 fatty acids on manifestations of coronary heart disease and
      ischemic stroke, whereas randomized, controlled, clinical feeding trials support
      this, particularly with respect to sudden cardiac death in patients with
      established disease. Clinically important anti-inflammatory effects in man are
      further suggested by trials demonstrating benefits of n-3 fatty acids in
      rheumatoid arthritis, psoriasis, asthma, and inflammatory bowel disorders. Given
      the evidence relating progression of atherosclerosis to chronic inflammation, the
      n-3 fatty acids may play an important role via modulation of the inflammatory
      processes.

PMID- 15485591
TI  - Diet and low-density lipoprotein particle size.
AB  - Small, dense low-density lipoprotein (LDL) particles are being increasingly
      recognized as an important risk factor for cardiovascular disease. This paper
      provides an overview of how different diets and macronutrients modulate the LDL
      size phenotype. Data reviewed indicated that several components of the LDL size
      phenotype should be measured concurrently in order to fully appreciate the impact
      of diet on this complex trait. Data also suggested that numerous dietary elements
      have a significant impact on several characteristics of the LDL size phenotype,
      thus providing further evidence to the concept that specific dietary
      modifications can beneficially alter cardiovascular disease risk beyond their
      known and demonstrated effects on plasma LDL cholesterol concentrations.

PMID- 15485593
TI  - Dietary fats and oils: technologies for improving cardiovascular health.
AB  - The role of dietary lipids in the etiology of coronary heart disease (CHD)
      continues to evolve as we gain a better understanding of the metabolic effects of
      individual fatty acids and their impact on surrogate markers of risk. A recent
      meta-analysis of 60 human studies suggests that for each 1% energy replacement of
      carbohydrates in the diet with saturated fat or trans fat, serum low-density
      lipoprotein cholesterol concentrations increase by 0.032 (1.23 mg/dL) and 0.04
      mmol/L (1.54 mg/dL), respectively. Current dietary recommendations to keep
      saturated fat and trans fat intake as low as possible, and to increase the intake
      of cis mono-unsaturated and polyunsaturated fatty acids, as well as growing
      recognition of these recommendations by consumers and food regulatory agencies in
      the United States, have been major driving forces for the edible oil industry and
      food manufacturers to develop alternative fats and oils with nutritionally
      improved fatty acid compositions. As solutions for use of trans fatty acids are
      being sought, oilseeds with modified fatty acid compositions are being viewed as
      a means to provide such solutions. Additionally, oilseeds with modified fatty
      acid composition, such as enhanced content of long-chain omega-3 fatty acids or
      conjugated linoleic acid, have been developed as a way to increase delivery of
      these fatty acids directly into the food supply or indirectly as use for feed
      ingredients for livestock. New processing technologies are being utilized around
      the world to create dietary fats and oils with specific physiologic functions
      relevant to risk factors for cardiovascular disease.

PMID- 15485594
TI  - Postprandial lipid oxidation and cardiovascular disease risk.
AB  - A mild pro-oxidative state accompanies meal ingestion, which results in an
      increase in biomarkers of inflammation, adhesion, and endothelial dysfunction,
      all of which are factors in the development of cardiovascular disease. Both fat
      and carbohydrate can cause the effect, which is additive and exacerbated by
      diabetes. The presence of lipid, glucose, and cholesterol oxidation products of
      dietary or endogenous origin may contribute to postprandial oxidative stress.
      However, the generation of excess superoxide due to abundant energy substrate
      after the meal may be a predominate factor resulting in oxidative stress and a
      decrease in nitric oxide, which is important to endothelial function. Remediation
      of postprandial oxidative stress through direct reduction of superoxide
      generation and simultaneous consumption of antioxidants with each meal should be
      a focus of future research.

PMID- 15485595
TI  - Effects of omega-3 fatty acids on cytokines and adhesion molecules.
AB  - The dietary intake of omega-3 (n-3) polyunsaturated fatty acids has emerged, over
      the past 20 years, as an important way to modify cardiovascular risk. This likely
      occurs through beneficial effects at all stages in the natural history of
      vascular disease, from the inception of atherosclerotic lesions, to their growth
      and acute complications (plaque rupture in most instances), up to protection of
      myocardium from the consequences of ensuing acute myocardial ischemia. This
      review specifically focuses on the modulating effects of n-3 fatty acids on
      biologic events involved in early atherogenesis, including important properties
      of these natural substances on endothelial expression of adhesion molecules and
      cytokines, processes collectively denoted as "endothelial activation." By
      decreasing the endothelial responsiveness to proinflammatory and proatherogenic
      stimuli, n-3 fatty acids act on molecular events not targeted by any other drugs
      or interventions, and thereby complementary to those of already implemented
      pharmacologic treatments.

PMID- 15485597
TI  - Restenosis following percutaneous coronary arterial intervention: what should the
      clinician do in order to identify and treat this complication?

PMID- 15485596
TI  - A dietary portfolio: maximal reduction of low-density lipoprotein cholesterol
      with diet.
AB  - Over the past two decades, cholesterol-lowering drugs have proven to be effective
      and have been found to significantly reduce the risk of coronary heart disease
      (CHD). However, diet and lifestyle factors are still recognized as the first line
      of intervention for CHD risk reduction by the National Cholesterol Education
      Program and the American Heart Association, which now advocate use of viscous
      fibers and plant sterols, and soy protein and nuts, respectively. In a series of
      metabolically controlled studies, we have combined these four cholesterol
      lowering dietary components in the same diet (ie, a dietary portfolio of
      cholesterol-lowering foods) in an attempt to maximize low-density lipoprotein
      cholesterol reduction. We have found that the portfolio diet reduced low-density
      lipoprotein cholesterol by approximately 30% and produced clinically significant
      reductions in CHD risk. These reductions were the same as found with a starting
      dose of a first-generation statin drug.

PMID- 15485599
TI  - Antihypertensive drugs and the heart.
AB  - Left ventricular hypertrophy (LVH) and diastolic dysfunction (CHF-D) are early
      signs of cardiac end-organ damage (hypertensive heart disease) in patients with
      arterial hypertension. The presence of LVH or CHF-D confers increased risk of
      cardiovascular morbidity and mortality in patients with hypertension. Regression
      of left ventricular mass with antihypertensive therapy is associated with
      reduction in cardiovascular events. Antihypertensive therapy should be geared to
      both lower blood pressure and specifically reverse the pathophysiologic processes
      that may be independent of actual blood pressure. This review summarizes current
      and emerging approaches to the treatment of individuals with hypertensive heart
      disease.

PMID- 15485598
TI  - Antihypertensive drugs and the kidney.
AB  - In the United States, 50 million Americans are estimated to have hypertension.
      Over the past several decades, it has become clear that hypertension is both a
      cause and a consequence of kidney disease. In contrast to the striking decline in
      mortality rates from both stroke and coronary heart disease, the prevalence of
      hypertension as a cause of end-stage renal disease (ESRD) has increased such that
      it is now the second most common cause of ESRD in the United States. Hypertension
      and proteinuria occur in most patients with chronic kidney disease and are risk
      factors for faster progression of kidney disease. Antihypertensive agents reduce
      blood pressure and urine protein excretion and slow the progression of kidney
      disease. The level of blood pressure achieved and use of renin-angiotensin
      aldosterone system-blocking agents is critical for delaying progression of renal
      disease in all ethnic groups.

PMID- 15485600
TI  - Hypertension in black patients: special issues and considerations.
AB  - The excess risk of hypertension in black Americans continues to be a major health
      concern. Although there is considerable information regarding these disease
      trends, much of the major underpinnings of the etiology of hypertension remain
      unclear. The excess mortality in blacks due to heart disease, renal failure, and
      stroke are clearly directly related to the excess burden of hypertension. Amid
      the recent findings about the pathophysiology of hypertension, some clear
      differences in the effects of overweight, salt sensitivity, and vascular biology
      emerge along ethnic lines. These differences may shed some light on the
      development of more effective treatment strategies. Based on our current
      knowledge, aggressive management of hypertension in blacks is critical. This
      review highlights what is known about various factors affecting hypertension and
      its treatment in black Americans.

PMID- 15485601
TI  - Combination drug treatment of hypertension: have we come full circle?
AB  - Only 30% of hypertensive patients achieved and maintained adequate blood pressure
      control on a single drug in recent clinical trials. For the majority of patients
      who require two or more drugs to lower blood pressure to the currently
      recommended goals of 140/90 mm Hg or to 130/80 if they are diabetic or have
      chronic kidney disease, combinations of two or more drugs in a single pill offers
      an attractive alternative to taking multiple single drugs each day. Research has
      shown that the simpler the drug regimen the more likely patients are to be
      compliant in taking medications. Because a reduction in cardiovascular risk is
      linked to the extent to which elevated blood pressure is reduced, this benefit is
      not realized by patients who either discontinue their medications or are
      noncompliant. Carefully selected low doses of two antihypertensive drugs combined
      in a single pill offers other advantages including greater efficacy compared with
      high-dose monotherapy, a lower incidence of adverse effects, improved persistence
      in taking medications, fewer patient visits, and reduced cost to the health care
      system.

PMID- 15485602
TI  - Hypertension and the metabolic syndrome.
AB  - The metabolic syndrome is a highly prevalent condition in the United States and
      it has been estimated from the Third National Health and Nutrition Examination
      Survey that approximately 40 million individuals fulfill the diagnostic criteria,
      which include a waist circumference greater than 40 inches in men and 35 inches
      in women, triglycerides in excess of 150 mg/dL, and a high-density lipoprotein
      cholesterol under 40 mg/dL in men or under 50 mg/dL in women. Additionally, a
      blood pressure in excess of 130/85 mm Hg and a fasting plasma glucose above 110
      mg/dL is required. The diagnosis of the metabolic syndrome requires at least
      three of the five major criteria for qualification. Hypertension, dyslipidemia,
      and diabetes frequently cluster and share common pathogenetic mechanisms,
      resulting in a complex interplay between these apparently disparate risk factors.
      This review centers on the common metabolic pathways that are common to the major
      conditions seen in the metabolic syndrome, and centers on the central role of
      hypertension and the clinical impact of drug therapy on other metabolic
      parameters.

PMID- 15485603
TI  - Coronary atherosclerosis progression by intravascular ultrasound with intensive
      versus moderate lipid lowering.

PMID- 15485604
TI  - Recombinant apolipoprotein A-I Milano effects on coronary atherosclerosis.

PMID- 15485605
TI  - Ezetimibe: a novel cholesterol-lowering agent that highlights novel physiologic
      pathways.
AB  - Ezetimibe is a US Food and Drug Administration-approved novel drug that targets
      the absorption of cholesterol in the intestine. The identification of this drug
      has also led to the elucidation of the dietary cholesterol receptor. Ezetimibe is
      efficacious as a plasma cholesterol-lowering agent as monotherapy, but its
      greatest utility seems to be as a combination with a low-dose statin, where it
      results in cholesterol lowering that is equivalent to using maximum-dose statins.
      It has a very favorable side-effect profile, as well as a lack of drug-drug
      interactions. In addition, it prevents the absorption of noncholesterol sterols,
      such as plant sterols. In clinical studies, it has been shown to be highly
      efficacious in lowering plant sterols in a rare genetic disorder, sitosterolemia.
      Both the disease, as well as this therapeutic agent, have led to the concept that
      ezetimibe may be also useful in dissecting the role of these noncholesterol
      sterols in the pathogenesis of atherosclerosis.

PMID- 15485606
TI  - Treatment of lipids and type 2 diabetes.
AB  - The development of type 2 diabetes is increasing in epidemic proportions. There
      is a significant risk for cardiovascular disease, which is the most prevalent and
      detrimental complication for the diabetic population. Serum lipid abnormalities
      are common in patients with diabetes, and due to this increased vascular risk, it
      is recommended to aggressively treat the hyperlipidemia. Therefore, intensive
      lipid-lowering therapy should be used for primary and secondary prevention
      against macrovascular complications for patients with type 2 diabetes. In this
      article some of the key studies justifying the need for lipid reduction in
      patients with type 2 diabetes are reviewed and practical guidelines for
      management of the dyslipidemia are suggested.

PMID- 15485607
TI  - Hypothyroidism and dyslipidemia: modern concepts and approaches.
AB  - Subclinical and overt hypothyroidism are relatively common disorders in the
      general population. Thyroid hormone is known to play a role in regulating the
      synthesis, metabolism, and mobilization of lipids. In patients with overt
      hypothyroidism there is an increase in serum total cholesterol, low-density
      lipoprotein (LDL) cholesterol, apolipoprotein B, lipoprotein(a) levels, and
      possibly triglyceride levels. The effects of subclinical hypothyroidism on serum
      lipid values are less clear. The preponderance of evidence suggests that total
      cholesterol, LDL cholesterol, and possibly triglycerides are increased in
      patients with subclinical hypothyroidism, whereas high-density lipoprotein (HDL)
      cholesterol and Lp(a) remain unchanged. Most lipid abnormalities in patients with
      overt hypothyroidism will resolve with thyroid hormone replacement therapy.
      However, clinical trials to date have not shown a beneficial effect of thyroid
      hormone treatment on serum lipid levels in patients with subclinical
      hypothyroidism. The lipid-altering effects of thyroid hormone make it an
      appealing target for drug development. The development of specifically targeted
      thyroid hormone analogues that could potentially treat hyperlipidemia without
      causing systemic thyrotoxicosis is currently ongoing.

PMID- 15485608
TI  - Addressing cardiovascular risk beyond low-density lipoprotein cholesterol: the
      high-density lipoprotein cholesterol story.
AB  - A large body of evidence from numerous, well-controlled, randomized trials
      demonstrates that treatment with statins reduce morbidity and mortality from
      cardiovascular disease (CVD). Although these observations are important and have
      resulted in the adoption of standard of care approaches to the management of CVD
      risk, they do not tell the whole story. When reviewing these landmark trials it
      is clear that on average two thirds of events are not prevented. This leads to
      the evaluation of risk beyond low-density lipoprotein cholesterol. This review
      focuses on the association of low high-density lipoprotein (HDL) cholesterol and
      increased CVD risk, the published trials that study the effect of raising HDL
      cholesterol on CVD outcomes, and the novel approaches toward HDL cholesterol
      raising that are on the horizon.

PMID- 15485610
TI  - Recent reminders of why the gold standard for clinical research in oncology is
      the well-designed and conducted randomized phase III trial.

PMID- 15485609
TI  - Aggressive diets and lipid responses.
AB  - Poor diet and physical inactivity, the two major contributors to the development
      of overweight and obesity, have recently been identified as the second most
      common actual cause of death in the United States. With the increasing awareness
      of the strong link between obesity and chronic disease, in particular
      cardiovascular disease, a myriad of diets have surfaced and many of them claim
      weight loss depends more on the macronutrient composition of the diet than the
      number of calories consumed. Long-term outcome data, particularly cardiovascular
      outcome data, on these diets are sparse. This article summarizes previous and
      recent reports of popular and aggressive diets, such as low-carbohydrate diets,
      low-fat diets, and very low-calorie diets, addressing their effects on weight
      loss and focusing on their effects on lipids and lipoproteins.

PMID- 15485611
TI  - Issues and challenges in palliative care for children with cancer.
AB  - Although the majority of children with cancer are cured of their illness, the
      children who die from their disease or complications require special care at the
      end of life. We present special issues and challenges unique to pediatric
      palliative care and suggest ways in which we can face these issues and address
      the challenges. The care must be family centered and balance the needs of the
      health-care system, the child, and the family. The way in which the care is
      delivered, the services provided, and the place in which that care is given are
      not carved into a simple protocol. Quality of life is an important concept that
      is often overlooked. Educational initiatives for patients, families, health-care
      providers, and third-party payers are essential. Reimbursement for palliative
      care services presents a large barrier to provision of appropriate services to
      all children and families in need. Hypothesis-driven research must be developed
      to help us learn more about how best to deliver end-of-life care to children and
      their families.

PMID- 15485612
TI  - Brain tumors in children.
AB  - Pediatric brain tumors are a challenging group of very divergent diseases.
      Considerable controversy exists concerning the accurate diagnosis and treatment
      of these patients. Aggressive therapy is often needed to cure aggressive and
      potentially lethal disease, yet late effects, especially injury to the developing
      brain, remain a profound problem. The discipline of pediatric neuro-oncology
      remains one of the most productive areas for continued clinical and basic
      research because of these and other challenges.

PMID- 15485614
TI  - First-line chemotherapy trial in advanced endometrial carcinoma.

PMID- 15485613
TI  - Molecular analysis of pediatric brain tumors.
AB  - The identification of molecular genetic abnormalities in specific types of
      pediatric brain tumors is beginning to play a role in the stratification of
      patients into treatment groups. The finding of an INI1 alteration in an atypical
      teratoid/rhabdoid tumor or malignant neoplasm with overlapping histologic
      features will be required for entry onto disease-specific protocols within the
      Children's Oncology Group. Refinement in the classification of medulloblastoma
      and malignant glioma patients will likely depend on the genetic and signaling
      pathways that characterize these tumors. Advances in this area will depend on the
      ability to identify new disease genes, validate prognostic markers, and develop
      biologically based therapeutic strategies to tailor treatment.

PMID- 15485615
TI  - Proteomics in cancer screening and management in gynecologic cancer.
AB  - Biomarkers are used routinely for population screening, disease diagnosis and
      prognosis, monitoring of therapy, and prediction of therapeutic response.
      Unfortunately, most biomarkers have low sensitivity and specificity and little
      predictive value. Novel techniques for better screening and early diagnosis of
      ovarian cancer are urgently needed. Proteomics, the study of the cellular
      proteins and their activation states, integrates some fundamental techniques,
      including high-throughput protein purification and profiling, genomic and
      proteomic databases, and mass spectrometry. In oncology, proteomics will
      contribute greatly to our understanding of gene functions in tumor development
      and provide information in clinical applications. This article reviews proteomic
      techniques and their potential applications in gynecologic cancer screening and
      management.

PMID- 15485616
TI  - A critical overview of concurrent chemoradiotherapy in cervical cancer.
AB  - In February 1999, the National Cancer Institute of the US National Institutes of
      Health issued a communication stating that concurrent chemoradiotherapy should be
      considered as standard treatment for cervical cancer. This statement was based on
      the publication of five randomized prospective trials. On the basis of a critical
      review of these papers and others that identified different results, questions,
      doubts, and concerns have arisen about this therapeutic method. We analyzed the
      quality of the control groups managed with the standard treatment, noting data
      that may have altered these results, as well as analyzing the quality of
      chemotherapy, radiotherapy, and treatment compliance. In light of this analysis,
      we believe that further trials should be carried out with fairly balanced
      prognostic factors to demonstrate beyond a doubt that concurrent
      chemoradiotherapy is superior to radiotherapy alone. In developing countries
      where resources are scarce, this type of tumor is found frequently. Concurrent
      chemoradiotherapy would involve increased costs and supportive care, taking away
      resources from other vital areas.

PMID- 15485617
TI  - Endometrial cancer: the management of high-risk disease.
AB  - Patients with endometrial cancer have an overall good prognosis. Patients with
      tumors invading deep into the myometrium or the cervical stroma or with
      extrauterine spread and patients with uterine papillary serous carcinoma (UPSC)
      or clear cell carcinoma (CCC) are at increased risk of relapse and represent a
      therapeutic challenge. Surgical treatment remains the cornerstone of therapy.
      Hysterectomy with bilateral salpingo-oophorectomy, washings, and careful
      assessment for intra-abdominal tumor should be performed with pelvic and para
      aortic lymph node dissection when indicated based on grade of tumor and depth of
      invasion. All patients with UPSC or CCC should have pelvic and para-aortic lymph
      node dissection and omentectomy performed. Gross extrauterine disease should be
      resected. Radiotherapy has been the traditional adjuvant treatment for all high
      risk patients. For patients with advanced disease (stage III-IV) combination
      chemotherapy with cisplatin and doxorubicin has been found to be superior to
      radiotherapy. For patients with advanced disease, treatment with a three-drug
      combination of cisplatin, doxorubicin, and paclitaxel has been shown to increase
      survival. It remains to be seen whether adjuvant chemotherapy in patients with
      high-risk disease in a lower stage will improve survival and possibly replace
      adjuvant radiotherapy in some patient groups.

PMID- 15485618
TI  - Gestational trophoblastic neoplasia: the management of relapsing patients and
      other recent advances.
AB  - The treatment of gestational trophoblastic neoplasia (GTN) represents one of the
      modern success stories in cancer medicine. Early diagnosis, effective treatments,
      monitoring of response with a series of serum human chorionic gonadotropin
      levels, and centralized care have all contributed to this success. Nevertheless,
      some patients relapse after initial chemotherapy. This review discusses the
      routine management of GTN and how to treat relapsed disease.

PMID- 15485619
TI  - Screening for cancer: valuable or not?
AB  - Screening for cancer has become extremely common. The evidence supporting
      screening for breast, colon, and cervix cancer is strong, but it is unclear for
      skin cancer, problematic for prostate cancer, and ineffective for lung cancer.
      Despite the problems associated with many screening approaches for cancer,
      enthusiasm by the medical profession and the public remains high. The objective
      analysis for the major tumor types is presented in this review, but the ultimate
      decision on whether to be screened lies in the personal and societal arena of
      values.

PMID- 15485620
TI  - Screening and early detection of skin cancer.
AB  - Skin cancer is the most common type of cancer in the United States. US incidence
      of malignant melanoma is increasing faster than any other type of cancer. To
      minimize increasing morbidity and mortality rates, it is imperative that
      appropriate screening and early detection of skin cancer become more widespread.
      All physicians who see patients clinically have the potential for detecting skin
      cancers. The scope of skin cancer as a health-care problem is discussed. Evidence
      for the effectiveness and necessity of skin cancer screening and early detection
      is presented. Costs of screening and detection are discussed in relation to
      impact on treatment costs and overall costs of skin cancer burden. Current
      methods and recommendations for skin cancer screening and detection are reviewed,
      especially with regard to individuals and populations that may require more
      specialized or intensive screening and follow-up. Newer approaches involving
      instrument-assisted screening and detection of skin cancer are under intense
      development, and these exciting emerging technologies are reviewed.

PMID- 15485622
TI  - Id3 knockout mice as a new model for sjogren's syndrome: only a T cell defect or
      more?
AB  - Id3(-/-) mice were found to have autoantibodies, lymphocytic infiltrates in, and
      decreased secretion by exocrine glands. Similar symptoms are found in primary
      Sjogren's Syndrome. In this issue of Immunity, Li and colleagues suggest an
      important role for Id3 function in T cell development and Sjogren's Syndrome.

PMID- 15485621
TI  - Cervical cancer screening.
AB  - Although primary prevention of human papillomavirus (HPV) infections that are
      causally associated with invasive cervical cancer may be within our grasp, it is
      unlikely that these approaches will replace existing cervical cancer screening
      strategies for many years. Experts agree and data support periodic cytology
      screening for young-adult women using one of several technologies. Recent
      analyses of cost-effectiveness suggest that the addition of molecular HPV DNA
      testing for women aged over 30 years may allow the screening interval to be
      lengthened to 3 years for most women. Women at high risk for HPV infection and
      its associated cellular atypias warrant closer monitoring and follow-up. These
      patients would include organ transplant recipients, women exposed to
      diethylstilbestrol (DES), and HIV-infected women.

PMID- 15485623
TI  - Retinoic acid: an educational "vitamin elixir" for gut-seeking T cells.
AB  - T cell priming by dendritic cells (DC) from gut-associated lymphoid tissues gives
      rise to effector cells with pronounced gut tropism. The mechanism for DC
      dependent imprinting of gut specificity has remained unknown. New findings point
      to retinoic acid, which is uniquely produced by intestinal DC, but not by DC from
      other lymphoid organs.

PMID- 15485624
TI  - Life and death decisions: secondary complexes and lipid rafts in TNF receptor
      family signal transduction.
AB  - Signaling by receptors in the TNF receptor (TNFR) superfamily mediate biological
      outcomes ranging from inflammation to apoptosis and other forms of programmed
      cell death. How receptor signaling mediates these divergent responses is just
      beginning to be understood. Here, we discuss how receptor submembrane
      localization and the formation of alternate signaling complexes can alter the
      fate of cells stimulated through TNFRs with a death domain, also known as "death
      receptors."

PMID- 15485625
TI  - Interleukin-17 family members and inflammation.
AB  - IL-17A was cloned more than 10 years ago and six IL-17 family members (IL-17A-F)
      have subsequently been described. IL-17A is largely produced by activated memory
      T lymphocytes but stimulates innate immunity and host defense. IL-17A and IL-17F
      both mobilize neutrophils partly through granulopoeisis and CXC chemokine
      induction, as well as increased survival locally. IL-17A and IL-17F production by
      T lymphocytes is regulated by IL-23 independent of T cell receptor activation.
      Increasing evidence shows that IL-17 family members play an active role in
      inflammatory diseases, autoimmune diseases, and cancer. This places IL-17 family
      members and their receptors as potential targets for future pharmacotherapy.

PMID- 15485626
TI  - Receptor-specific signaling for both the alternative and the canonical NF-kappaB
      activation pathways by NF-kappaB-inducing kinase.
AB  - The NF-kappaB-inducing kinase (NIK) induces proteolytic processing of NF
      kappaB2/p100 and, hence, the generation of NF-kappaB dimers such as p52:RelB but
      was suggested not to signal for the processing of IkappaB. Here, we show that
      although the induction of IkappaB degradation in lymphocytes by TNF is
      independent of NIK, its induction by CD70, CD40 ligand, and BLyS/BAFF, which all
      also induce NF-kappaB2/p100 processing, does depend on NIK function. Both CD70
      and TNF induce recruitment of the IKK kinase complex to their receptors. In the
      case of CD70, but not TNF, this process is associated with NIK recruitment and is
      followed by prolonged receptor association of just IKK1 and NIK. Recruitment of
      the IKK complex to CD27, but not that of NIK, depends on NIK kinase function. Our
      findings indicate that NIK participates in a unique set of proximal signaling
      events initiated by specific inducers, which activate both canonical and
      noncanonical NF-kappaB dimers.

PMID- 15485627
TI  - TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans
      signaling.
AB  - Alterations of TGF-beta signaling have been described in colorectal cancer,
      although the molecular consequences are largely unknown. By using transgenic mice
      overexpressing TGF-beta or a dominant-negative TGF-betaRII, we demonstrate that
      TGF-beta signaling in tumor infiltrating T lymphocytes controls the growth of
      dysplastic epithelial cells in experimental colorectal cancer, as determined by
      histology and a novel system for high-resolution chromoendoscopy. At the
      molecular level, TGF-beta signaling in T cells regulated STAT-3 activation in
      tumor cells via IL-6. IL-6 signaling required tumor cell-derived soluble IL-6R
      rather than membrane bound IL-6R and suppression of such TGF-beta-dependent IL-6
      trans-signaling prevented tumor progression in vivo. Taken together, our data
      provide novel insights into TGF-beta signaling in colorectal cancer and suggest
      novel therapeutic approaches for colorectal cancer based on inhibition of TGF
      beta-dependent IL-6 trans-signaling.

PMID- 15485628
TI  - Role of LAG-3 in regulatory T cells.
AB  - Regulatory T cells (Tregs) limit autoimmunity but also attenuate the magnitude of
      antipathogen and antitumor immunity. Understanding the mechanism of Treg function
      and therapeutic manipulation of Tregs in vivo requires identification of Treg
      selective receptors. A comparative analysis of gene expression arrays from
      antigen-specific CD4(+) T cells differentiating to either an effector/memory or a
      regulatory phenotype revealed Treg-selective expression of LAG-3, a CD4-related
      molecule that binds MHC class II. Antibodies to LAG-3 inhibit suppression by
      induced Tregs both in vitro and in vivo. Natural CD4(+)CD25(+) Tregs express LAG
      3 upon activation, which is significantly enhanced in the presence of effector
      cells, whereas CD4(+)CD25(+) Tregs from LAG-3(-/-) mice exhibit reduced
      regulatory activity. Lastly, ectopic expression of LAG-3 on CD4(+) T cells
      significantly reduces their proliferative capacity and confers on them suppressor
      activity toward effector T cells. We propose that LAG-3 marks regulatory T cell
      populations and contributes to their suppressor activity.

PMID- 15485629
TI  - T cell division and death are segregated by mutation of TCRbeta chain constant
      domains.
AB  - We have studied the role of the T cell receptor (TCR) beta chain transmembrane
      and cytoplasmic domains (betaTM/Cyto) in T cell signaling. Upon antigen
      stimulation, T lymphocytes expressing a TCR with mutant and betaTM and Cyto
      domains accumulate in large numbers and are specifically defective in undergoing
      activation-induced cell death (AICD). The mutant TCR poorly recruits the protein
      adaptor Carma-1 and is subsequently impaired in activating NF-kappaB. This
      signaling defect leads to a reduced expression of Fas ligand (FasL) and to a
      reduction in AICD. These beta chain domains are involved in discriminating cell
      division and apoptosis.

PMID- 15485630
TI  - Retinoic acid imprints gut-homing specificity on T cells.
AB  - For a preferential homing of T cells to the gut, expression of the integrin
      alpha4beta7 and the chemokine receptor CCR9 is essential and is induced by
      antigenic stimulation with dendritic cells from the gut-associated lymphoid
      organs. Here, we show that the vitamin A (retinol) metabolite, retinoic acid,
      enhances the expression of alpha4beta7 and CCR9 on T cells upon activation and
      imprints them with the gut tropism. Dendritic cells from the gut-associated
      lymphoid organs produced retinoic acid from retinol. The enhanced alpha4beta7
      expression on T cells by antigenic stimulation with these dendritic cells was
      suppressed by the retinal dehydrogenase inhibitor citral and the retinoic acid
      receptor antagonist LE135. Accordingly, vitamin A deficiency caused a reduction
      in alpha4beta7(+) memory/activated T cells in lymphoid organs and a depletion of
      T cells from the intestinal lamina propria. These findings revealed a novel role
      for retinoic acid in the imprinting of gut-homing specificity on T cells.

PMID- 15485631
TI  - Osteopontin as a mediator of NKT cell function in T cell-mediated liver diseases.
AB  - Both osteopontin (OPN) and natural killer T (NKT) cells play a role in the
      development of immunological disorders. We examined a functional link between OPN
      and NKT cells. Concanavalin A (Con A)-induced hepatitis is a well-characterized
      murine model of T cell-mediated liver diseases. Here, we show that NKT cells
      secrete OPN, which augments NKT cell activation and triggers neutrophil
      infiltration and activation. Thus, OPN- and NKT cell-deficient mice were
      refractory to Con A-induced hepatitis. In addition, a neutralizing antibody
      specific for a cryptic epitope of OPN, exposed by thrombin cleavage, ameliorated
      hepatitis. These findings identify NKT cell-derived OPN as a novel target for the
      treatment of inflammatory liver diseases.

PMID- 15485632
TI  - A T cell intrinsic role of Id3 in a mouse model for primary Sjogren's syndrome.
AB  - Sjogren's syndrome is an autoimmune disease with clinical hallmarks of
      keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth). The genetic
      basis of this autoimmune disease is poorly understood. Id3 is an immediate early
      response gene in growth regulation and is involved in TCR-mediated T cell
      selection during T cell development. Here, we show that Id3-deficient mice
      develop many disease symptoms found in primary Sjogren's syndrome patients
      including dry eyes and mouth, lymphocyte infiltration in lachrymal and salivary
      glands, and development of anti-Ro and anti-La antibodies. Adoptive transfer
      experiment indicated a T cell intrinsic role for Id3 in the development of
      Sjogren's symptoms. Furthermore, genetic ablation of T cells or neonatal 3 day
      thymectomy in Id3-deficient mice showed a rescue of disease symptoms, suggesting
      a thymic origin of autoimmune T cells. Thus, this study establishes a critical
      connection between Id3-mediated T cell development and autoimmune diseases.

PMID- 15485633
TI  - Dyslipidemia associated with atherosclerotic disease systemically alters
      dendritic cell mobilization.
AB  - High LDL and/or low HDL are risk factors for atherosclerosis and are also a
      common clinical feature in systemic lupus erythematosus, rheumatoid arthritis,
      and psoriasis. Here, we show that changes in lipid profiles that reflect
      atherosclerotic disease led to activation of skin murine dendritic cells (DCs)
      locally, promoted dermal inflammation, and induced lymph node hypertrophy.
      Paradoxically, DC migration to lymph nodes was impaired, suppressing immunologic
      priming. Impaired migration resulted from inhibitory signals generated by
      platelet-activating factor (PAF) or oxidized LDL that acts as a PAF mimetic.
      Normal DC migration and priming was restored by HDL or HDL-associated PAF
      acetylhydrolase (PAFAH), which mediates inactivation of PAF and oxidized LDL.
      Thus, atherosclerotic changes can sequester activated DCs in the periphery where
      they may aggravate local inflammation even as they poorly carry out functions
      that require their migration to lymph nodes. In this context, HDL and PAFAH
      maintain a normally functional DC compartment.

PMID- 15485634
TI  - Act1, a negative regulator in CD40- and BAFF-mediated B cell survival.
AB  - TNF receptor (TNFR) superfamily members, CD40, and BAFFR play critical roles in B
      cell survival and differentiation. Genetic deficiency in a novel adaptor
      molecule, Act1, for CD40 and BAFF results in a dramatic increase in peripheral B
      cells, which culminates in lymphadenopathy and splenomegaly,
      hypergammaglobulinemia, and autoantibodies. While the B cell-specific Act1
      knockout mice displayed a similar phenotype with less severity, the pathology of
      the Act1-deficient mice was mostly blocked in CD40-Act1 and BAFF-Act1 double
      knockout mice. CD40- and BAFF-mediated survival is significantly increased in
      Act1-deficent B cells, with stronger IkappaB phosphorylation, processing of NF
      kappaB2 (p100/p52), and activation of JNK, ERK, and p38 pathways, indicating that
      Act1 negatively regulates CD40- and BAFF-mediated signaling events. These
      findings demonstrate that Act1 plays an important role in the homeostasis of B
      cells by attenuating CD40 and BAFFR signaling.

PMID- 15485635
TI  - Human T regulatory cells can use the perforin pathway to cause autologous target
      cell death.
AB  - Cytotoxic T lymphocytes and natural killer cells use the perforin/granzyme
      pathway to kill virally infected cells and tumor cells. Mutations in genes
      important for this pathway are associated with several human diseases. CD4(+) T
      regulatory (Treg) cells have emerged as important in the control of
      immunopathological processes. We have previously shown that human adaptive Treg
      cells preferentially express granzyme B and can kill allogeneic target cells in a
      perforin-dependent manner. Here, we demonstrate that activated human
      CD4(+)CD25(+) natural Treg cells express granzyme A but very little granzyme B.
      Furthermore, both Treg subtypes display perforin-dependent cytotoxicity against
      autologous target cells, including activated CD4(+) and CD8(+) T cells, CD14(+)
      monocytes, and both immature and mature dendritic cells. This cytotoxicity is
      dependent on CD18 adhesive interactions but is independent of Fas/FasL. Our
      findings suggest that the perforin/granzyme pathway is one of the mechanisms that
      Treg cells can use to control immune responses.

PMID- 15485636
TI  - Comparative proteomic analysis of human whole saliva.
AB  - Human saliva performs a wide variety of biological functions that are critical
      for the maintenance of the oral health. Various functions include lubrication,
      buffering, antimicrobial protection, and the maintenance of mucosal integrity. In
      addition, whole saliva may be analysed for the diagnosis of human systemic
      diseases, since it can be readily collected and contains identifiable serum
      constituents. By using proteomic approach, we have established a reference
      proteome map of human whole saliva allowing for the resolution of greater than
      200 protein spots in a single two-dimensional polyacrylamide gel. Fifty-four
      protein spots, comprised of 26 different proteins, were identifies using N
      terminal sequencing, mass spectrometry, and/or computer matching with protein
      database. Ten proteins, whose levels were significantly different when bleeding
      had occurred in the oral cavity, were discussed in this study. These 10 proteins
      include alpha-1-antrypsin, apolipoprotein A-I, cystatin A, SA, SA-III, and SN,
      enolase I, hemoglobin beta-chain, thioredoxin peroxiredoxin B, as well as a
      prolactin-inducible protein. The proteomic approach identifies candidates from
      human whole saliva that may prove to be of diagnostic and therapeutic
      significance.

PMID- 15485637
TI  - Effect of psychological stress on the salivary cortisol and amylase levels in
      healthy young adults.
AB  - OBJECTIVE: Saliva sampling has the advantage that it is non-invasive, making
      multiple sampling easy and stress free. We examined the effects of psychological
      stressor and soother on the salivary cortisol and amylase levels in young adults,
      and compared the characteristics of these parameters. DESIGN: The subjects
      completed the trait version of State-Trait Anxiety Inventory (STAI) to assess the
      predisposition to personal anxiety. The video of corneal transplant surgery was
      served as the stressor for 15 min. A scenic beauty video viewing was also used as
      the soother. Unstimulated whole saliva was collected every 3 min throughout the
      session. RESULTS: The amylase level was significantly increased just after the
      beginning of the stressful video viewing, and immediately returned to the pre
      stress level just after the end of the video viewing. The cortisol level was also
      increased, but to a lesser extent compared with that of amylase. The latency time
      to the peak level for cortisol was longer than that of amylase. The carry-over
      effect was not observed in the amylase response but was in cortisol. Although the
      correlation between the amylase level and the STAI score was highly significant,
      cortisol level did not. In addition, soothing video viewing significantly
      decreased the amylase level, but did not affect the cortisol level. CONCLUSION:
      Salivary amylase level was more significantly increased and reacted more rapidly
      than cortisol by psychological stressor, suggesting that it is a better index of
      stress. Furthermore, it is suggested that the enzyme is a soothing or relaxation
      index.

PMID- 15485638
TI  - The xerogenic potency and mechanism of action of tramadol inhibition of salivary
      secretion in rats.
AB  - Tramadol is a centrally acting analgesic with weak opioid agonist properties,
      which also has monoaminergic activity, exerted via inhibition of neuronal uptake
      of serotonin and norepinephrine. Tramadol is generally well tolerated and the
      most common adverse events are nausea, dizziness, drowsiness, sweating, vomiting
      and dry mouth. Currently it was examined by which principal mechanism tramadol
      induces oral dryness. The effects of intravenous administration (+/-)-tramadol
      were studied in rats on the flow of saliva in response to a peripheral
      cholinergic stimulus or to reflex activation involving the relay of impulses in
      the central nervous system. In pentobarbitone-anaesthetized rats, the salivary
      secretion to acetylcholine (0.1-10 micromol/kg IV) was increased by up to 110% by
      tramadol (1-5 mg/kg IV) and the protein concentration therein by up to 400%. The
      administration alpha- and beta-adrenoceptor antagonists resulted in almost
      identical acetylcholine-evoked responses as in the absence of tramadol. The
      secretory response to the application of citric acid on the tongue of the rat was
      reduced by 38% and by 64%, respectively, at 5 and 10 mg/kg IV of tramadol (p <
      0.05-0.01). Thus, tramadol exerts its principal xerogenic effect by activating
      inhibitory pathways in the central nervous system and has no anticholinergic
      effect on the salivary glands at dosages that may be clinically relevant.
      Furthermore, the tramadol-induced increase of the acetylcholine-evoked secretion
      occurred at a glandular level and depended most likely on a release of
      noradrenaline from glandular nerve terminals.

PMID- 15485639
TI  - Presence of cytoskeleton proteins in parotid glands and their roles during
      secretion.
AB  - Amylase secretion is induced by the accumulation of cAMP in response to beta
      adrenergic stimulation and by the augmentation of intracellular Ca2+ in response
      to muscarinic-cholinergic stimulation in rat parotid glands. The roles of
      cytoskeleton and motor proteins in the secretory process are not yet known. We
      examined the effects of cytoskeleton-modulating reagents on the amylase release
      induced by isoproterenol (IPR) and carbamylcholine (Cch) in rat parotid acinar
      cells. The amylase release induced by Cch was decreased by the microtubule
      disrupting reagent colchicine (Colch) and the myosin ATPase inhibitor 2,3
      butanediene monoxime (BDM), but the release induced by IPR was not. The actin
      filament-stabilizing reagent jasplakinolide (Jasp) and actin filament-disrupting
      reagent cytochalasin D (CytoD) decreased the amylase release induced by both the
      beta-adrenergic and the muscarinic-cholinergic stimulants. Pretreatment with
      CytoD affected the shape of the acinar cells, which showed an intermediate state
      between the fusion of the secretory granules with the apical membrane and the
      retrieval of the membranes only after stimulation with IPR. Myosin and
      Dynein/dynactin complex were detected in the secretory granule membrane fraction.
      We concluded from this study that the cytoskeleton played different roles in the
      beta-adrenergic and the muscarinic-cholinergic secretory processes.

PMID- 15485640
TI  - Functional influence of masticatory muscles on the fibre characteristics and
      capillary distribution in growing ferrets (Mustela putonusfuro)--a histochemical
      analysis.
AB  - OBJECTIVE: Changes in the masticatory function of ferrets have been shown to
      cause alterations in their craniofacial morphology. The aim of the present study
      was to investigate how the functional changes influence the histochemical
      characteristics of fibres of the masticatory muscles of the animal. DESIGN: Forty
      five-week old male ferrets were divided into two groups: one group was fed a diet
      of hard pellets (HD group), and one group was fed the same diet but softened with
      water (SD group). After 6 months, specimens of temporalis, masseter and
      digastricus were taken from each ferret and prepared for enzyme histochemical
      analysis RESULTS: Type I muscle fibres constituted the majority of the temporalis
      and the masseter, while the digastricus mainly comprised type II muscle fibres.
      The fibre-type composition did not differ significantly between the two groups.
      The mean cross-sectional area of type I and type II fibres in the temporalis and
      the masseter, and type II fibres in the digastricus was significantly greater in
      the HD group than the SD group. Furthermore, the HD group had a significantly
      greater number of capillaries per fibre, but not per surface unit (mm2).
      CONCLUSIONS: The results suggest that the muscle fibre size and the number of
      capillaries per fibre of the masticatory muscles are readily adaptesd to the
      altered masticatory muscle functions.

PMID- 15485641
TI  - Reducing within-subject variation in chewing cycle kinematics--a statistical
      approach.
AB  - OBJECTIVES: High levels of within-subject variability have limited the use of
      chewing cycle kinematics in the experimental and clinical context. The purpose of
      this study was to validate a new strategy for reducing within-subject variability
      in chewing cycle kinematics, based on the 10 most representative cycles from a
      chewing sequence. METHODS: This prospective study included 25 young subjects,
      with normal class I occlusions. An optoelectronic recording system was used to
      track chin movements of subjects chewing gum (2.5 g). Computer programs provided
      estimates for duration and movement as well as the 3D coordinates of the chin
      point. The total output files were further processed for selection of 10
      representative cycles based on standard scores for total duration, excursive
      ranges in the lateral, vertical and antero-posterior directions. Multilevel
      modelling procedures were used to test for significant differences. RESULTS:
      There were no significant differences in cycle duration or excursions between the
      estimates for all cycles versus the 10 most representative cycles. Cycle shapes
      were very similar. There were no statistically significant differences in between
      subject variances. All within-subject variances were smaller when using data from
      the 10 most representative cycles. The reduction of variance was approximately
      33% for total duration and 75% for total 3D excursion. CONCLUSIONS: The results
      validate the pre-processing strategy that selects the 10 most representative
      cycles from a sequence without altering cycle duration, excursions or shape or
      affecting between-subject variation but reducing within-subject variation
      substantially.

PMID- 15485642
TI  - The association between the masseter muscle, the mandibular alveolar bone mass
      and thickness in dentate women.
AB  - OBJECTIVE: Since muscle strength has been demonstrated to affect the bone in the
      long bones and spine, the possibility exists that the bone mass and dimension of
      the alveolar processes could be influenced by the function of the masticatory
      muscles. Therefore, the purpose of this study was to investigate whether two
      local factors (ultrasonographic masseter thickness, and occluding teeth) plus the
      skeletal bone mineral density (BMD) affect the mandibular alveolar bone mass
      (MABM) and the bucco-lingual alveolar thickness of the alveolar process. DESIGN:
      The thickness of the masseter muscle was evaluated by ultrasound imaging in 62
      dentate women (40-75 years) with no periodontal disease and no dental infection
      in the premolar region consecutively selected from the patients in a public
      dental clinic. MABM was evaluated using periapical radiographs. The bucco-lingual
      thickness of the alveolar process was measured on dental casts with a dial
      calliper. BMD of the forearm was determined with dual energy X-ray
      absorptiometry. RESULTS: Multiple regression analyses demonstrated that masseter
      thickness and the number of occluding mandibular teeth in the lateral segment
      were significant determinants of MABM and of the interdental thickness, but BMD
      was not. The number of years after menopause and struma/gastro-intestinal disease
      influenced MABM but not the alveolar thickness. CONCLUSION: The local factors
      played an important role in the posterior mandibular segment and their effect
      might partly explain the low correlation between MABM and skeletal BMD.

PMID- 15485643
TI  - Long-wave cycles in the position of erupting human premolars.
AB  - OBJECTIVE: Unusual long-wave cycles in the position of an erupting human premolar
      were first noted by Trentini et al. [Trentini CJ, Brown WH, Paterson RL, Proffit
      WR. The application of Moire magnification to high precision studies of human
      premolar eruption. Arch Oral Biol 1995;40:623-9]. This report characterises them
      in detail and evaluates their significance relative to human tooth eruption.
      DESIGN: The magnitude and frequency of Trentini cycles were examined in high
      resolution recordings of premolar eruption in patients without and with
      periapical infiltration of a vasoconstrictor or vasodilator, and the possibility
      of artifact due to the natural frequency of vibration of a tooth-PDL system or to
      building vibration was evaluated. RESULTS: The cycles are characterised by a
      magnitude of 1.3 +/- 0.5 microm and a frequency of 1.8 +/- 0.5 cycles per minute,
      with greater variation between than among subjects. They cannot be explained as a
      natural frequency phenomenon, and vibration from microseism is highly unlikely.
      The cycles disappear when blood flow to the periapical area of the tooth is
      interrupted and reappear when blood flow resumes. CONCLUSIONS: The cycles appear
      to reflect a physiologic rhythm, probably related to blood flow in the
      periodontal ligament. Because they are similar whether or not a tooth is erupting
      at a particular time, however, it appears that they are not a direct reflection
      of a blood flow-related eruption mechanism.

PMID- 15485644
TI  - Genetic contribution to dental arch size variation in Australian twins.
AB  - The aim of this study was to quantify the relative contributions of genetic and
      environmental factors to variations in dental arch breadth, length and palatal
      height in a sample of Australian twins, and to estimate heritabilities using
      modern model-fitting methods. Dental casts of 20 male and 24 female monozygous
      (MZ) twin pairs, 17 male and 8 female dizygous (DZ) twin pairs, and 9 opposite
      sexed DZ twin pairs were selected from the collection of records of twins housed
      at the Adelaide Dental School. The mean ages of subjects were 15.8 +/- 3.5 years
      (MZ) and 17.0 +/- 4.7 years (DZ). Dental casts were scanned using a contact-type
      3D scanner, PICZA interfaced to a personal computer running 3D-Rugle3 software.
      Data were subjected to univariate genetic analysis with the structural equation
      modelling package, Mx, using the normal assumptions of the twin model. A model
      incorporating additive genetic (A) and unique environmental (E) variation was
      found to be the most parsimonious for dental arch breadth and length, and palatal
      height. Estimates of heritability for dental arch breadth ranged from 0.49 to
      0.92, those for arch length from 0.86 to 0.94, and those for palatal height were
      0.80 and 0.81, respectively. These results indicate a high genetic contribution
      to the variation in dental arch dimensions in mainly teenage twins.

PMID- 15485645
TI  - Basic fibroblast growth factor up-regulates the expression of vascular
      endothelial growth factor during healing of allogeneic bone graft.
AB  - Recently we reported that basic fibroblast growth factor (bFGF) improved the
      healing of allogeneic bone grafts. However, the mechanism of action of the bFGF
      was not known. Therefore, the present study was designed to identify the
      expression pattern of vascular endothelial growth factor (VEGF) in the presence
      of bFGF reconstituted in demineralized intramembranous bone matrix (DBMIM) during
      the healing of allogeneic bone grafts. Eighteen critical size (15 mm x 10 mm)
      defects were created on rabbit mandibles bilaterally. Three groups of six defects
      each were grafted with allogeneic bone alone, allogeneic bone and DBMIM, and
      allogeneic bone and bFGF reconstituted in DBMIM. Three weeks later, the defects
      were retrieved for immunohistochemistry and in situ hybridization for VEGF. The
      percentage of positive staining area was quantified by using image analyzer. The
      increase (517%) in the expression of VEGF mRNA was accompanied by an increase
      (492%) of immunoreactive VEGF protein in allogeneic bone graft augmented by bFGF
      reconstituted in DBMIM. A close correlation existed between levels of VEGF
      production and the amount of newly formed bone. The results show that bFGF
      reconstituted in DBMIM markedly up-regulated the expression of VEGF in the
      grafted area. Basic FGF augments the healing of allogeneic bone grafts by
      enhancing vascularization through the up-regulation of VEGF.

PMID- 15485646
TI  - Suppression of inferior alveolar nerve-induced vasoconstrictor response by
      ongoing cervical sympathetic nerve activity in cat.
AB  - We examined the effects of ongoing cervical sympathetic trunk (CST) stimulation
      on the vasoconstrictor responses in the lower lip elicited by electrical
      stimulation (ES) of the inferior alveolar nerve (IAN) or CST in anaesthetised
      cats to determine whether (i) the previously reported suppressive effect of
      ongoing CST activity on IAN-induced vasoconstriction occurs during not only
      ipsilateral, but also contralateral CST stimulation; and (ii) a vasoconstriction
      can be elicited by brief CST stimulation during ongoing stimulation of the
      contralateral CST. The central lower lip blood vessels are innervated by both
      left and right CST. The fall in central lip blood flow (LBF) elicited by IAN
      stimulation alone was reduced in a frequency-dependent manner during concurrent
      CST stimulation at 0.2-2 Hz, and at the high end of this frequency range was
      transformed to a rise regardless of whether the CST stimulation was ipsilateral
      or contralateral to the IAN stimulation. The fall in central LBF elicited by
      stimulation of one CST was not transformed to a rise by ongoing stimulation of
      the contralateral CST. Possibly, IAN-evoked orofacial vasoconstriction does not
      occur under physiological conditions (unlike IAN-evoked vasodilatation) because
      it is suppressed by the spontaneous sympathetic discharge in CST.

PMID- 15485647
TI  - Human herpesvirus 6 in oral fluids from healthy individuals.
AB  - BACKGROUND: Human herpesvirus 6 (HHV6) is the etiologic agent of exanthem
      subitum. The virus is latent in salivary glands and saliva is the main form of
      viral transmission. The objective of this study was to assess HHV6 incidence in
      the fluids from healthy individuals using a standardised technique for collecting
      and extracting viral DNA from gingival crevicular fluid, whole saliva and parotid
      gland saliva. DESIGN: Samples of oral fluids and peripheral blood were collected
      from 28 blood donors and HHV6 was detected using PCR assay. Parotid gland saliva
      and gingival crevicular fluid were collected by endodontic paper cones in order
      to not contaminate these fluids with whole saliva. RESULTS: Of the 28 donors, 20
      (71.4%) presented positive results in at least one of the three oral fluids
      researched. Whole saliva was positive in 19 (67.8%) volunteers, while only four
      (14.2%) samples of gingival crevicular fluid and four of parotid gland saliva
      proved to be positive. CONCLUSIONS: The results suggest that HHV6 is present in
      the saliva of a large proportion of the healthy adult population. The use of
      endodontic paper cones for oral fluid collection and viral extraction was
      efficient, simple, cheap and painless. In spite of, the small number of cases
      studied it was possible to demonstrate that neither gingival crevicular fluid nor
      parotid gland saliva were the principal source of HHV6 in whole saliva.

PMID- 15485648
TI  - A technical consideration concerning the removal of oocyte vitelline membranes
      for patch clamp recording.
AB  - We have developed an efficient method for removing the vitelline membrane of
      Xenopus oocytes for patch clamp recording. Functional studies using oocytes as
      models provide insights into the biological profiles and physiological properties
      of ion channels. A methodological modification is described in this paper. The
      important feature of this modification is that protease treatment is used to
      remove the oocyte's vitelline membrane. This method is simple and the oocytes
      produced remain in a healthy state during the recording process.

PMID- 15485649
TI  - ZAK re-programs atrial natriuretic factor expression and induces hypertrophic
      growth in H9c2 cardiomyoblast cells.
AB  - Various intracellular or intercellular stimuli have been associated with the
      development of cardiac cell hypertrophy. However, the mechanisms underlying this
      association are not completely understood. In a previous study we determined that
      ZAK mRNA expression is abundant in heart. ZAK is a mitogen-activated protein
      kinase kinase kinase (MAP3K) that activates the stress-activated protein kinase/c
      jun N-terminal kinase pathway and activates NF-kappaB. We, therefore,
      investigated the potential involvement of ZAK (which in cultured H9c2
      cardiomyoblast cell is a positive mediator of cell hypertrophy). Our results
      showed that the expression of a wild-type form of ZAK induces the characteristic
      hypertrophic growth features, including increased cell size, elevated atrial
      natriuretic factor expression, and increased actin fiber organization.

PMID- 15485650
TI  - Ammodytoxin, a neurotoxic secreted phospholipase A(2), can act in the cytosol of
      the nerve cell.
AB  - Recent identification of intracellular proteins that bind ammodytoxin
      (calmodulin, 14-3-3 proteins, and R25) suggests that this snake venom
      presynaptically active phospholipase A(2) acts intracellularly. As these
      ammodytoxin acceptors are cytosolic and mitochondrial proteins, the toxin should
      be able to enter the cytosol of a target cell and remain stable there to interact
      with them. Using laser scanning confocal microscopy we show here that Alexa
      labelled ammodytoxin entered the cytoplasm of the rat hippocampal neuron and
      subsequently also its nucleus. The transport of proteins into the nucleus
      proceeds via the cytosol of a cell, therefore, ammodytoxin passed the cytosol of
      the neuron on its way to the nucleus. Although it is not yet clear how
      ammodytoxin is translocated into the cytosol of the neuron, our results
      demonstrate that its stability in the cytosol is not in question, providing the
      evidence that the toxin can act in this cellular compartment.

PMID- 15485651
TI  - IGF-1 phosphorylates AMPK-alpha subunit in ATM-dependent and LKB1-independent
      manner.
AB  - Serine/threonine protein kinase AMP-activated protein kinase (AMPK) is a key
      metabolic stress-responsive factor that promotes the adaptation of cells to their
      microenvironment. Elevated concentrations of intracellular AMP, caused by
      metabolic stress, are known to activate AMPK by phosphorylation of the catalytic
      subunit. Recently, the tumor suppressor serine/threonine protein kinase LKB1 was
      identified as an upstream kinases, AMPKKs. In the current study, we found that
      stimulation with growth factors also caused AMPK-alpha subunit phosphorylation.
      Interestingly, even an LKB1-nonexpressing cancer cell line, HeLa, exhibited
      growth factor-stimulated AMPK-alpha subunit phosphorylation, suggesting the
      presence of an LKB1-independent pathway for AMPK-alpha subunit phosphorylation.
      In the human pancreatic cancer cell line PANC-1, AMPK-alpha subunit
      phosphorylation promoted by IGF-1 was suppressed by antisense ataxia
      telangiectasia mutated (ATM) expression. We found that IGF-1 also induced AMPK
      alpha subunit phosphorylation in the human normal fibroblast TIG103 cell line,
      but failed to do so in a human fibroblast AT2-KY cell line lacking ATM.
      Immunoprecipitates of ATM collected from IGF-1-stimulated cells also caused the
      phosphorylation of the AMPK-alpha subunit in vitro. IGF-1-stimulated ATM
      phosphorylation at both threonine and tyrosine residues, and our results
      demonstrated that the phosphorylation of tyrosine in the ATM molecule is
      important for AMPK-alpha subunit phosphorylation during IGF-1 signaling. These
      results suggest that IGF-1 induces AMPK-alpha subunit phosphorylation via an ATM
      dependent and LKB1-independent pathway.

PMID- 15485652
TI  - Organization of functional domains in the docking protein p130Cas.
AB  - The docking protein p130Cas becomes phosphorylated upon cell adhesion to
      extracellular matrix proteins, and is thought to play an essential role in cell
      transformation. Cas transmits signals through interactions with the Src-homology
      3 (SH3) and Src-homology 2 domains of FAK or v-Crk signaling molecules, or with
      14-3-3 protein, as well as phosphatases PTP1B and PTP-PEST. The large (130kDa),
      multi-domain Cas molecule contains an SH3 domain, a Src-binding domain, a serine
      rich protein interaction region, and a C-terminal region that participates in
      protein interactions implicated in antiestrogen resistance in breast cancer. In
      this study, as part of a long-term goal to examine the protein interactions of
      Cas by X-ray crystallography and nuclear magnetic resonance spectroscopy,
      molecular constructs were designed to express two adjacent domains, the serine
      rich domain and the Src-binding domain, that each participate in intermolecular
      contacts dependent on protein phosphorylation. The protein products are soluble,
      homogeneous, monodisperse, and highly suitable for structural studies to define
      the role of Cas in integrin-mediated cell signaling.

PMID- 15485653
TI  - A single nucleotide polymorphism in the matrix metalloproteinase-2 promoter is
      associated with colorectal cancer.
AB  - Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against
      matrix proteins, particularly basement membrane constituents. A single nucleotide
      polymorphism C-->T transition at -1306, which disrupts an Sp1-type promoter site
      (CCACC box), displayed a strikingly lower promoter activity with T allele. Our
      study investigated whether the MMP-2 -1306 C-->T polymorphism contributed to the
      development and progression of colorectal cancer in the Chinese population. One
      hundred twenty-six colorectal cancer patients and 126 age- and sex-matched
      controls were included in this study. PCR-based denaturing high performance
      liquid chromatography analysis and sequencing were used to determine the MMP-2
      genotypes. MMP-2 expression of each genotype was analyzed in four colorectal
      cancer cell lines by semi-quantitative RT-PCR. The correlation between the
      genotypes and clinicopathological parameters among colorectal cancer cases was
      investigated. The results showed that the levels of MMP-2 mRNA expression in cell
      lines containing CC genotype were much higher compared with cell with CT
      genotype. The frequency of MMP-2 CC genotype was significantly higher in
      colorectal cancer patients when compared with controls (OR, 1.959; 95% CI, 1.055
      3.637). Colorectal cancers with CC genotype were more common with
      serosa/adventitia layer involvement compared with CT+TT genotypes. Our data
      suggest that MMP-2 -1306 C-->T polymorphism may be associated with colorectal
      cancer development and invasion in the Chinese population.

PMID- 15485654
TI  - Recycling of the dense-core vesicle membrane protein phogrin in Min6 beta-cells.
AB  - Phogrin (IA2-beta) is an integral membrane protein of dense-core vesicles in
      neuroendocrine cells. We have examined the recycling of endogenous phogrin
      following exocytosis in insulin secreting Min6 beta-cells by monitoring stimulus
      dependent-uptake of antibodies directed against the lumenal domain of the
      protein. While low levels of internalized phogrin accumulated in LAMP1-positive
      lysosomes, more than 35% of internalized phogrin recycled back to an insulin
      positive compartment and could return to the cell surface during a second
      exocytic stimulation. The recycling phogrin transited a syntaxin 6-positive
      compartment but did not appear to go through the TGN38-positive trans Golgi
      network. The results suggest a model in which secretory membrane components can
      recycle from the endosomal system to immature secretory granules without
      interaction with the major portion of the TGN.

PMID- 15485655
TI  - SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to
      EGF stimulation.
AB  - The control of cellular responses with fibroblast growth factors and
      neurotrophins is mediated through membrane-linked docking proteins, SNT (suc1
      binding neurotrophic target)-1/FRS2alpha and SNT-2/FRS2beta. ERK1/2 are members
      of the mitogen-activated protein kinase family that regulate diverse cellular
      activities in response to various stimuli. Here, we demonstrate that SNT-2 does
      not become tyrosine phosphorylated significantly in response to EGF but forms a
      complex with ERK2 via the region of 186-252 amino acid residues, and the complex
      formation is enhanced upon EGF stimulation. SNT-2 downregulates ERK2
      phosphorylation, suppresses and delays ERK2 nuclear accumulation which occurs
      following EGF stimulation. In contrast, the mutant SNT-2 which carries deletion
      of 186-252 amino acids and lacks ERK2 binding does not have these effects. These
      observations suggest that SNT-2 negatively regulates ERK2 signaling activated via
      EGF stimulation through direct binding to ERK2.

PMID- 15485656
TI  - Phosphatidylinositol 3-kinase inhibitors reveal a unique mechanism of enhancing
      insulin secretion in 832/13 rat insulinoma cells.
AB  - Hyperinsulinemia exists before the onset of overt type 2 diabetes mellitus. This
      response is at least partly due to enhanced insulin release from pancreatic beta
      cells. Increased insulin secretion can be mimicked in vitro by acute culture of
      832/13 rat insulinoma cells with phosphatidylinositol 3-kinase (PI-3K)
      inhibitors, a treatment that would theoretically simulate insulin resistance. We
      demonstrate in this study that while the PI-3K inhibitors Wortmannin and LY294002
      both block Akt phosphorylation, only LY29002 significantly augments insulin
      secretion. LY294002 treatment potentiates insulin secretion over both basal and
      stimulatory glucose concentrations. This effect correlates with a significant
      increase in action potential duration. There was no change in resting or peak
      membrane potential under any of the treatment conditions, demonstrating that the
      cells remain healthy under the acute treatments used in this study. By contrast,
      Wortmannin has no effect on action potential duration. A partial explanation for
      these findings is that LY294002 potently inhibits voltage-dependent potassium
      channels, but does not affect voltage-gated calcium currents. We conclude that
      while PI-3K may play a role in regulating insulin secretion, there are diverse
      effects of the established inhibitors of this enzyme on beta-cell insulin
      secretory responses.

PMID- 15485657
TI  - Molecular cloning of Rab5 (ApRab5) in Aiptasia pulchella and its retention in
      phagosomes harboring live zooxanthellae.
AB  - The intracellular association of symbiotic dinoflagellates (zooxanthellae) with
      marine cnidarians is the very foundation of the highly productive and diversified
      coral reef ecosystems. To reveal its underlying molecular mechanisms, we
      previously cloned ApRab7, a Rab7 homologue of the sea anemone Aiptasia pulchella,
      and demonstrated its selective exclusion from phagosomes containing live
      zooxanthellae, but not from those containing either dead or photosynthesis
      impaired algae. In this study, Rab5 was characterized, due to its key role in
      endocytosis and phagocytosis acting upstream of Rab7. The Aiptasia Rab5 homologue
      (ApRab5) is 79.5% identical to human Rab5C and contains all Rab-specific
      signature motifs. Subcellular fractionation study showed that ApRab5 is mainly
      cytosolic. EGFP reporter and phagocytosis studies indicated that membrane
      associated ApRab5 is present in early endocytic and phagocytic compartments, and
      is able to promote their fusion. Significantly, immunofluorescence study showed
      that the majority of phagosomes containing either resident or newly internalized
      live zooxanthellae were labeled with ApRab5, while those containing either heat
      killed or photosynthesis-impaired algae were mostly negative for ApRab5 staining
      whereas the opposite was observed for ApRab7. We propose that active phagosomal
      retention of ApRab5 is part of the mechanisms employed by live zooxanthellae to:
      (1) persist inside their host cells and (2) exclude ApRab7 from their phagosomes,
      thereby, establishing and/or maintaining an endosymbiotic relationship with their
      cnidarian hosts.

PMID- 15485658
TI  - A cloned prokaryotic Cd2+ P-type ATPase increases yeast sensitivity to Cd2+.
AB  - CadA, the P1-type ATPase involved in Listeria monocytogenes resistance to Cd(2+),
      was expressed in Saccharomyces cerevisiae and did just the opposite to what was
      expected, as it strikingly decreased the Cd(2+) tolerance of these cells. Yeast
      cells expressing the non-functional mutant Asp(398)Ala could grow on selective
      medium containing up to 100 microM Cd(2+), whereas those expressing the
      functional protein could not grow in the presence of 1 microM Cd(2+). The CadA
      GFP fusion protein was localized in the endoplasmic reticulum membrane,
      suggesting that yeast hyper-sensitivity was due to Cd(2+) accumulation in the
      reticulum lumen. CadA is also known to transport Zn(2+), but Zn(2+) did not
      protect the cells against Cd(2+) poisoning. In the presence of 10 microM Cd(2+),
      transformed yeasts survived by rapid loss of their expression vector.

PMID- 15485659
TI  - Pleiotrophin is an important regulator of the renin-angiotensin system in mouse
      aorta.
AB  - To better understand the phenotype of pleiotrophin (PTN the protein, Ptn the
      gene) genetically deficient mice (Ptn -/-), we compared the transcriptional
      profiles of aortae obtained from Ptn -/- and wild type (WT, Ptn +/+) mice using a
      14,400 gene microarray chip (Affymetrix) and confirmed the analysis of relevant
      genes by real time RT-PCR. We found striking alterations in expression levels of
      different genes of the renin-angiotensin system of Ptn -/- mice relative to WT
      (Ptn +/+) mice. The mRNA levels of the angiotensin converting enzyme (ACE) were
      significantly decreased in Ptn -/- mice whereas the mRNA levels of the
      angiotensin II type 1 (AT1) and angiotensin II type 2 (AT2) receptors were
      significantly increased in Ptn -/- mice when they were compared with mRNA levels
      in WT (Ptn +/+) mice aortae. These data demonstrate for the first time that the
      levels of expression of the Ptn gene markedly influence expression levels of the
      genes encoding the key proteins of the renin-angiotensin system in mouse aorta
      and suggest the tentative conclusion that levels of Ptn gene expression have the
      potential to critically regulate the downstream activities of angiotensin II,
      through the regulation of its synthesis by ACE and its receptor mediated
      functions through regulation of both the AT1 and AT2 receptors.

PMID- 15485660
TI  - An alpha-subunit loop structure is required for GM2 activator protein binding by
      beta-hexosaminidase A.
AB  - The alpha- and/or beta-subunits of human beta-hexosaminidase A (alphabeta) and B
      (betabeta) are approximately 60% identical. In vivo only beta-hexosaminidase A
      can utilize GM2 ganglioside as a substrate, but requires the GM2 activator
      protein to bind GM2 ganglioside and then interact with the enzyme, placing the
      terminal GalNAc residue in the active site of the alpha-subunit. A model for this
      interaction suggests that two loop structures, present only in the alpha-subunit,
      may be critical to this binding. Three amino acids in one of these loops are not
      encoded in the HEXB gene, while four from the other are removed
      posttranslationally from the pro-beta-subunit. Natural substrate assays with
      forms of hexosaminidase A containing mutant alpha-subunits demonstrate that only
      the site that is removed from the beta-subunit during its maturation is critical
      for the interaction. Our data suggest an unexpected biological role for such
      proteolytic processing events.

PMID- 15485661
TI  - WGEF is a novel RhoGEF expressed in intestine, liver, heart, and kidney.
AB  - Rho family GTPases regulate multiple cellular processes through their downstream
      effectors, where their activities are stimulated by the guanine nucleotide
      exchange factors. Here, we report a new member of RhoGEF, WGEF, which has the
      classical structure of DH-PH domain and a C-terminal SH3 domain. WGEF was shown
      to activate RhoA, Cdc42, and Rac1 by pulldown assay, and forced expression of
      WGEF resulted in marked rearrangement of the actin cytoskeleton, which is
      typically seen by the activation of RhoA, Cdc42, and Rac1. WGEF was highly
      expressed in intestine and also in liver, heart and kidney, which may suggest the
      involvement of WGEF in the development and functions of these organs. The
      expression pattern may also suggest the possible importance of WGEF in the
      understanding of diseases based on metabolic disorder.

PMID- 15485662
TI  - Oxidation of phosphatidylserine: a mechanism for plasma membrane phospholipid
      scrambling during apoptosis?
AB  - Selective oxidation of phosphatidylserine (PS) during apoptosis precedes its
      externalization in plasma membrane and is essential for the engulfment of
      apoptotic cells. To experimentally test whether PS oxidation stimulates its
      externalization via its effects on aminophospholipid translocase (APT) or by
      enhanced PS scrambling, action of oxidized PS (PSox) was studied using leukemia
      HL-60 cells and lymphoma Raji cells. Both PS and PSox were equally well
      recognized by APT. PSox did not inhibit APT. Rate of transmembrane PS diffusion
      was fourfold higher in cells with integrated PSox than with PS. Thus, PSox acts
      as a "non-enzymatic scramblase" likely contributing to PS externalization.

PMID- 15485663
TI  - In Pseudomonas aeruginosa ethidium bromide does not induce its own degradation or
      the assembly of pumps involved in its efflux.
AB  - Xu et al. [Biochem. Biophys. Res. Commun. 305 (2003) 941] reported that, when a
      mutant strain of Pseudomonas aeruginosa lacking its major multidrug efflux pump
      complex, MexAB-OprM, was incubated with 100 microM ethidium bromide, the
      fluorescence, caused by its binding to DNA following its entry into cells,
      decreased gradually. The authors concluded that the intracellular ethidium
      bromide "induced" either its degradation or its efflux through the assembly of
      unknown efflux pumps. We found, through quantitation of ethidium bromide by
      absorption spectroscopy, that the total amount of ethidium bromide in the system
      remained constant under these conditions, indicating the absence of its
      degradation. Furthermore, intracellular ethidium bromide kept increasing during
      the experiment, showing that the decrease of fluorescence was due to self
      quenching, and that ethidium bromide is not pumped out by a newly assembled
      efflux system.

PMID- 15485664
TI  - Similarity in cyst wall protein (CWP) trafficking between encysting Giardia
      duodenalis trophozoites and CWP-expressing human embryonic kidney-293 cells.
AB  - Cyst wall proteins 1 and 2 (CWP1 and CWP2) are major constituents of the giardial
      cyst wall and are expressed with similar kinetics by encysting trophozoites. In
      the present study, we were interested to determine if the expression of giardial
      CWPs as heterologous proteins in a higher eukaryotic cell would result in their
      trafficking across the secretory pathway, as is the case in encysting
      trophozoites. Recombinant (r)CWP1 and rPro-CWP2 were detected in the lysate and
      culture media of transfected HEK-293 cells. We then conducted intracellular
      localization experiments using confocal microscopy and found that the proteins
      were trafficked in membrane enclosed vesicles across the secretory pathway and
      released to the culture medium by transfected HEK-293 cells. We then dissected
      the rCWP1 and rPro-CWP2 molecules to identify the portion(s) responsible for
      their secretion and found that the putative N-terminal signal peptide was
      sufficient for directing the secretion of rCWP1, while both the putative N
      terminal signal peptide and the 13kDa C-terminal regions were necessary for the
      secretion of rPro-CWP2 by transfected HEK-293 cells. Taken together, these
      results demonstrate the degree of conservation of signal peptide recognition
      between lower and higher eukaryotes.

PMID- 15485665
TI  - Protein crystal growth on board Shenzhou 3: a concerted effort improves crystal
      diffraction quality and facilitates structure determination.
AB  - The crystallization of 16 proteins was carried out using 60 wells on board
      Shenzhou 3 in 2002. Although the mission was only 7 days, careful and concerted
      planning at all stages made it possible to obtain crystals of improved quality
      compared to their ground controls for some of the proteins. Significantly
      improved resolutions were obtained from diffracted crystals of 4 proteins. A
      complete data set from a space crystal of the PEP carboxykinase yielded
      significantly higher resolution (1.46A vs. 1.87A), I/sigma (22.4 vs. 15.5), and a
      lower average temperature factor (29.2A(2) vs. 42.9A(2)) than the best ground
      based control crystal. The 3-D structure of the enzyme is well improved with
      significant ligand density. It has been postulated that the reduced convection
      and absence of macromolecule sedimentation under microgravity have
      advantages/benefits for protein crystal growth. Improvements in experimental
      design for protein crystal growth in microgravity are ongoing.

PMID- 15485666
TI  - Nontypeable Haemophilus influenzae lipoprotein P6 induces MUC5AC mucin
      transcription via TLR2-TAK1-dependent p38 MAPK-AP1 and IKKbeta-IkappaBalpha-NF
      kappaB signaling pathways.
AB  - Mucin overproduction is a hallmark of nontypeable Haemophilus influenzae (NTHi)
      infections. The molecular mechanisms underlying up-regulation of mucin in NTHi
      infections especially during the initial phase remain unknown. Here we show that
      P6, a 16-kDa outer membrane lipoprotein well conserved in NTHi, up-regulates
      MUC5AC mucin gene transcription in vitro and in vivo. Moreover, P6 induces MUC5AC
      transcription via TLR2-MyD88-IRAK1-TRAF6-TAK1-dependent p38 MAPK-AP1 and IKKbeta
      IkappaBalpha-NF-kappaB signaling pathways. This study may bring new insights into
      the molecular pathogenesis of NTHi-induced infections and lead to novel
      therapeutic intervention for inhibiting mucin overproduction in patients with
      NTHi infections.

PMID- 15485667
TI  - Steric effects of isoleucine 107 on heme reorientation reaction in human
      myoglobin.
AB  - Structural factors to regulate the heme reorientation reaction in myoglobin were
      examined and we found that the side chain at position 107 (Ile107), which is
      located between the 2-vinyl and 3-methyl groups of heme, forms a kinetic barrier
      for the heme rotation about the alpha-gamma axis. The phenylalanine-substituted
      mutant showed an extremely slow heme reorientation rate, compared to that of the
      wild-type protein, while replacement by the decreased side chain, valine, at
      position 107 accelerated the reorientation reaction. Considering that the
      spectroscopic data show only minor structural changes in the heme environments of
      the Ile107 mutants, the side chain at position 107 sterically interacts with the
      heme peripheral groups in the activation state for the heme reorientation, which
      supports the intramolecular mechanism that the heme rotates about the alpha-gamma
      axis without leaving the "protein cage."

PMID- 15485668
TI  - The herbicide 2,4-dichlorophenoxyacetic acid induces the generation of free
      radicals and associated oxidative stress responses in yeast.
AB  - The pro-oxidant action of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is
      demonstrated in this study using Saccharomyces cerevisiae as a eukaryotic
      experimental model. Evidence is presented for the generation of hydroxyl
      radicals, in yeast cells suddenly exposed to 2,4-D, detected by in vivo electron
      paramagnetic resonance (EPR) spectroscopy using 5,5'-dimethyl-1-pyrroline N-oxide
      and 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide as spin-traps. The
      intensity of the EPR spectra was dependent on the concentration of herbicide
      tested and was consistently higher in a mutant (Deltasod1) devoid of the
      cytosolic CuZn-superoxide dismutase. A time-course-dependent variation of the
      level of free-radical adducts was registered upon sudden exposure of an yeast
      cell population to concentrations of 2,4-D that lead to an initial period of
      viability loss, before resumption of inhibited growth by the viable adapted
      population. The variation pattern of the level of hydroxyl-radical adducts
      correlated with the one determined for the activity of Sod1p, cytosolic catalase
      Ctt1p, and the dithiol glutaredoxins Grx1p and Grx2p.

PMID- 15485669
TI  - Equine papillomavirus type 1: complete nucleotide sequence and characterization
      of recombinant virus-like particles composed of the EcPV-1 L1 major capsid
      protein.
AB  - Equus caballus papillomavirus type 1 (EcPV-1) was isolated from a cutaneous
      papilloma, the most common neoplasm in horses. The complete EcPV-1 nucleotide
      sequence and genomic organization were determined. Phylogenetic analysis showed
      that EcPV-1 is a close-to-root papillomavirus, with only distant relationships to
      the fibropapillomaviruses and the benign cutaneous papillomaviruses. To produce
      EcPV-1 virus-like particles (VLPs), the EcPV-1 L1 major capsid protein was
      expressed in insect cells using a recombinant baculovirus vector. The self
      assembled EcPV-1 VLPs were morphologically indistinguishable from wild type
      papillomavirus virions. Monoclonal antibodies were developed against intact and
      denatured EcPV-1 VLPs. When tested by ELISA, all monoclonal antibodies produced
      against intact (#18) and some against denatured EcPV-1 VLPs (#16) reacted with
      intact EcPV-1 VLPs only, demonstrating that the VLPs carry type-specific
      conformational as well as linear epitopes on their surface. Recombinant EcPV-1
      VLPs offer the potential of a noninfectious vaccine to prevent and eradicate
      equine cutaneous papillomatosis.

PMID- 15485670
TI  - Members of the histone deacetylase superfamily differ in substrate specificity
      towards small synthetic substrates.
AB  - Histone deacetylases (HDACs) are important enzymes for the transcriptional
      regulation of gene expression in eukaryotic cells. Deacetylation of epsilon
      acetyl-lysine residues within the N-terminal tail of core histones mediates
      changes in both histone-DNA and histone-non-histone protein interactions.
      However, surprisingly little is known about the substrate specificities of
      different HDACs. Here, we use the epsilon-acyl moieties of epsilon-modified l
      lysine in peptidic substrates as a probe to examine the active site cavity of
      HDACs and HDAC-like enzymes. Measurements were based on a fluorogenic assay with
      small synthetic substrates. Four different enzyme preparations were used derived
      from rat, human, and bacterial sources. None of the enzymes was able to utilize
      substrates with epsilon-acyl moieties larger than acetyl, except rat liver HDAC,
      which was the only enzyme to convert a substrate containing epsilon-propionyl-l
      lysine. All enzymes exhibited a distinct enantioselectivity toward l-lysine
      containing substrates except FB188 HDAH which also deacetylated Boc-d-Lys(epsilon
      acetyl)-MCA. Moreover, all enzymes also exhibited a distinct specificity for the
      length of the lysine side chain; acetylated ornithine, which comprises one CH(2)
      unit less in the side chain, was not a substrate. In line with these results,
      only acetylcadaverin the metabolic degradation product of lysine but neither
      acetylputrescine (degradation product of ornithine) nor acetylspermidine strongly
      inhibited enzyme activity. Boc-l-Lys(epsilon-trifluoroacetyl)-MCA was observed to
      be a superior substrate for FB188 HDAH, Pseudomonas aeruginosa HDAH (PA3774), and
      particularly HDAC 8 compared to rat liver HDAC, and is the first suitable
      (synthetic) substrate for (human-derived) HDAC 8 reported to date. Altogether,
      the results reveal clear differences in substrate specificity between different
      HDACs as analyzed in the fluorogenic HDAC assay. Finally, we present the first
      candidates for HDAC-type-selective substrates that may be useful as biochemical
      tools to establish the function of particular pathways and to elucidate the role
      of distinct HDAC subtypes in cellular differentiation and cancer.

PMID- 15485671
TI  - Assembly of alpha-hemolysin on A431 cells leads to clustering of Caveolin-1.
AB  - Assembly and penetration of 14-strand beta-barrel of staphylococcal alpha
      hemolysin (alpha-HL) is an intriguing phenomenon due to its water soluble
      property. alpha-HL interacts with the Caveolin-1 of A431 cells for its rapid
      assembly. A nine amino acid, non-hydrophobic peptide derived from alpha-HL has
      been shown to block the interaction of alpha-HL with the scaffolding domain of
      Caveolin-1. alpha-HL's presence was also detected in the Caveolin-1 enriched
      membrane fractions isolated by ultracentrifugation. Moreover, alpha-HL co
      precipitates with Caveolin-1 specifically. In a time-dependent process, alpha-HL
      associates with the Caveolin-1 and co-localizes with Caveolin-1 that results in
      an extensive clustering of Caveolin-1 at cell-cell contacts. Mutants of alpha-HL
      devoid of Caveolin-1 binding motif failed to assemble into heptameric oligomers
      on the surface of A431 cells. Our data suggest that the conformational changes
      required to form the heptameric assembly might be triggered at the Caveolin-1
      binding motif of alpha-HL.

PMID- 15485672
TI  - Functional form of Caveolin-1 is necessary for the assembly of alpha-hemolysin.
AB  - The assembly of alpha-HL was shown to rapidly progress upon its interaction with
      Caveolin-1. Treatment of A431 cells with alpha-HL has resulted in clustering of
      Caveolin-1 at cell-cell contacts. Consistent with this observation, alpha-HL
      mutants devoid of assembly property have not induced the clustering of Caveolin
      1. While cholesterol depletion of A431 cells completely arrests the assembly of
      alpha-HL, chelation of membrane cholesterol results in its retarded assembly.
      Interestingly, HT29 cells, with low Caveolin-1 levels, are resistant to alpha-HL
      attack. Clustering of Caveolin-1, as seen in case of A431 cells, was readily
      observed in case of HT29 cells transfected with Caveolin-1 construct, thus
      overexpressing the full length Caveolin-1, upon alpha-HL treatment. A model was
      constructed to visualize the interactions between alpha-HL and Caveolin-1 which
      suggests that facile penetration of alpha-HL's beta-barrel might occur through
      protein-protein interactions with the surrounding 7 alpha-helices of Caveolin-1.

PMID- 15485673
TI  - Cellular and subcellular localization of the inhibitory glycine receptor in
      hippocampal neurons.
AB  - Inhibitory glycine receptors are most abundant in spinal cord and brainstem, and
      glycinergic synapses have a well-established role in the regulation of locomotor
      behavior. Little is known about the function of glycine receptors in cortex and
      hippocampus, where GABA plays a dominant role in synaptic inhibition. Therefore,
      we have investigated tissue and cellular expression of glycine receptor alpha
      subunits. Western blot and immunohistochemical analyses reveal the presence of
      glycine receptors in hippocampal tissue. Immunocytochemical experiments in
      hippocampal cultures show prominent cellular expression of glycine receptors in
      pyramidal neurons and GAD-positive interneurons similar to the calcium-binding
      protein VILIP-1 with widespread hippocampal distribution. On the subcellular
      level we found co-staining of GlyR and the presynaptic marker synapsin I.
      Furthermore, co-staining with GAD at synaptic terminals indicated partial co
      localization of GABA- and glycine receptors.

PMID- 15485674
TI  - EGF signalling amplification induced by dynamic clustering of EGFR.
AB  - Lateral interaction is an important feature of various types of cell surface
      receptors including the receptor tyrosine kinases (RTKs). Here we report that
      dynamic lateral interaction produces amplification and variation in signalling of
      the EGF receptor, a member of RTKs. Binding of EGF is known to induce
      transphosphorylation inside EGFR dimers. Using single-molecule techniques, the
      relationship between EGF binding and EGFR phosphorylation has been determined.
      The number of phosphorylated EGFR molecules became larger than that of EGF
      binding as unliganded EGFR was phosphorylated, meaning an amplification of EGF
      signalling. EGFR formed clusters continuously exchanging their elements through
      thermal diffusion, and direct and/or indirect lateral interactions. As a result,
      various types of activation sites differing in number of activated receptors were
      generated. Amplification required no cytoplasmic factors and was observed on semi
      intact cells for a wide range of number of EGFR molecules (10(4)-10(6) per cell)
      suggesting generality of this process.

PMID- 15485675
TI  - Caveolae and EDHF production.

PMID- 15485676
TI  - Direct vasoprotection by aspirin: a significant bonus to antiplatelet activity?

PMID- 15485677
TI  - Cardiac cellular heterogeneity and remodelling.

PMID- 15485678
TI  - Regulation of mitochondrial proliferation in the heart: power-plant failure
      contributes to cardiac failure in hypertrophy.
AB  - During hypertrophy, proliferation of mitochondria does not keep pace with the
      increasing energy demand of the heart. This probably contributes importantly to
      cardiac failure, together with other phenotypic changes occurring during the
      growth process. The problem may be even aggravated if defects of mitochondrial
      function itself and not external factors cause the hypertrophic process. Here we
      review the basic mechanisms controlling mitochondrial biogenesis, especially the
      pathways coordinating expression of nuclear encoded mitochondrial genes and the
      small mitochondrial genome, and how these mechanisms may be connected to the
      cardiomyocyte differentiation program during development as well as under
      physiological and pathological circumstances.

PMID- 15485679
TI  - Current status of catheter- and stent-based gene therapy.
AB  - Significant progress has been made in the field of cardiovascular gene therapy
      over the past decade. Animal models of human disease have helped in identifying
      potential therapeutic genes and have also assisted in the evaluation of an ideal
      vector. A number of percutaneous catheter systems have been used in animal models
      with limited success. Stents represent an attractive alternative for localized
      gene delivery, as they provide a platform for prolonged gene elution and
      efficient transduction of opposed arterial walls. This gene delivery strategy has
      the potential to decrease the systemic spread of the viral vectors and hence a
      reduced host immune response. Both synthetic and naturally occurring stent
      coatings have shown potential to allow prolonged gene elution with no significant
      adverse reaction. However, further animal studies are required to evaluate the
      compatibility of stent coatings, vector solutions, and the arterial wall as well
      as assessment of the feasibility of this approach to achieve the full potential
      of gene therapy.

PMID- 15485680
TI  - Does altered glucocorticoid homeostasis increase cardiovascular risk?
AB  - The hypothalamic-pituitary-adrenal (HPA) axis, like the sympathetic nervous
      system and the renin-angiotensin-aldosterone (RAA) system, sustains life in
      stressful situations by increasing vascular tone and ensuring fuel availability.
      It also modulates inflammation and tissue repair processes. Untoward
      cardiovascular effects of chronic sympathetic and RAA activation are well
      recognized, illustrating that the short-term benefit of the physiologic stress
      response can be detrimental in the long term. Similarly, chronic tissue exposure
      to glucocorticoids may lead to metabolic and vascular changes that accelerate
      vascular senescence. Specific situations associated with chronic activation of
      the HPA axis-such as major depression, inflammatory disease and perhaps the
      metabolic syndrome-may derive some of their associated cardiovascular risk from
      untoward glucocorticoid effects. Since there are no definitive clinical studies
      directly addressing the relationship between the HPA axis and cardiovascular
      disease, we present indirect evidence from two types of studies: (1) studies that
      examine the cardiovascular effects of exogenous glucocorticoids, and (2) studies
      demonstrating that endogenous glucocorticoid activity varies between individuals.
      The effects of physiologic increases in endogenous glucocorticoid activity may
      not always mirror the effects of supraphysiologic glucocorticoids. Nevertheless,
      the known effects of exogenous glucocorticoids provide important insights into
      the putative effects of endogenous glucocorticoids.

PMID- 15485681
TI  - Calsequestrin mutant D307H exhibits depressed binding to its protein targets and
      a depressed response to calcium.
AB  - OBJECTIVE: A point mutation in human cardiac calsequestrin (CSQ-D307H) is
      responsible for a form of polymorphic ventricular tachycardia (PVT). When
      overexpressed in heart cells, the mutated CSQ leads to diminished Ca(2+)
      transients, consistent with defective regulation of intralumenal sarcoplasmic
      reticulum (SR) Ca(2+). METHODS: To analyze the D307H mutant and determine whether
      the D307H mutation results in loss of normal protein-protein interactions, we
      prepared recombinant human wild-type (WT) and D307H forms of CSQ in mammalian
      cells. RESULTS: Although we found the two proteins to undergo similar
      glycosylation and phosphorylation, we discovered that Ca(2+)-dependent binding of
      the D307H mutant to both triadin-1 and junctin was reduced by greater than 50%
      compared to WT. Reduced binding of the D307H mutant CSQ to target proteins was
      similar throughout a complete range of Ca(2+) concentrations. To investigate the
      mechanism of reduced Ca(2+)-dependent binding, Ca(2+)-dependent changes in
      intrinsic fluorescence emission for the two protein forms were compared.
      Intrinsic fluorescence of the D307H mutant was highly reduced, reflecting
      significant alteration in the tertiary protein structure. Moreover, the changes
      in fluorescence caused by increasing the Ca(2+) concentration were very
      significantly blunted, indicating that the Ca(2+)-dependent conformational change
      was virtually lost. CONCLUSIONS: We conclude that the point mutation D307H leads
      to a profoundly altered conformation that no longer responds normally to Ca(2+)
      and fails to bind normally to triadin and junctin.

PMID- 15485682
TI  - Cholesterol- and caveolin-rich membrane domains are essential for phospholipase
      A2-dependent EDHF formation.
AB  - OBJECTIVE: Cholesterol-rich membrane domains, which contain the scaffold protein
      caveolin-1 (Cav-1) (caveolae), represent an important structural element involved
      in endothelial signal transduction. The present study was designed to investigate
      the role of these signaling platforms in the generation of endothelial-derived
      hyperpolarizing factor (EDHF). METHODS: Caveolae were disrupted by cholesterol
      depletion with methyl-beta-cyclodextrin (MbetaCD 10 mM). MbetaCD-induced
      modulation of non-nitric oxide-/non-prostanoid-dependent (EDHF)-mediated
      vasorelaxation was studied in pig coronary arteries. Effects of MbetaCD on
      endothelial Ca(2+) signaling and phospholipase A(2) (cPLA(2)) activity were
      determined using fura-2 imaging and measurement of [(3)H]-arachidonate
      mobilization in cultured pig aortic endothelial cells (PAEC). Cellular
      localization of caveolin-1 and phospholipase A(2) was investigated by cell
      fractionation, and interaction of cPLA(2) with caveolin-1 was tested by
      immunoprecipitation experiments. RESULTS: MbetaCD inhibited EDHF-mediated
      relaxations of pig coronary arteries induced by bradykinin (100 nM) or ionomycin
      (300 nM) but not relaxations induced by the NO donor DEA/NO (1 microM). Exposure
      of arteries to cholesterol-saturated MbetaCD failed to affect EDHF-mediated
      relaxations. Cholesterol depletion with MbetaCD did not affect bradykinin or
      ionomycin-induced Ca(2+) signaling in pig aortic endothelial cells, but was
      associated with enhanced basal and reduced Ca(2+)-dependent release of
      arachidonic acid (AA). Cell fractionation experiments indicated targeting of
      cPLA(2) to low density, caveolin-1 rich membranes and immunoprecipitation
      experiments demonstrated association of phospholipase A(2) with the scaffold
      protein of caveolae, caveolin-1. Cholesterol depletion with MbetaCD did not
      disrupt the interaction between cPLA(2) and caveolin-1 but prevented targeting of
      cPLA(2) to low density membranes. Exogenous supplementation of arachidonic acid
      after cholesterol depletion partially restored EHDF responses in pig coronary
      arteries. CONCLUSION: The integrity of caveolin-1-containing membrane
      microdomains is prerequisite for arachidonic acid recruitment and EDHF signaling
      in porcine arteries.

PMID- 15485683
TI  - Aspirin inhibits ox-LDL-mediated LOX-1 expression and metalloproteinase-1 in
      human coronary endothelial cells.
AB  - BACKGROUND: Aspirin is thought to exert salutary effects in vascular disease
      states by inhibiting platelet aggregation. Endothelial activation, accumulation
      of oxidized low-density lipoprotein (ox-LDL) and intense inflammation also
      characterize atherosclerotic plaque in acute myocardial ischemia. Ox-LDL induces
      expression of lectin-like receptors (LOX-1) on endothelial cells and leads to the
      expression of matrix metalloproteinases (MMPs), which destabilize the
      atherosclerotic plaque. We hypothesized that aspirin may interfere with LOX-1
      expression and subsequent MMP activation. METHODS AND RESULTS: Cultured human
      coronary artery endothelial cells (HCAECs) were incubated with aspirin (1-5 mM),
      sodium salicylate (5 mM) or the cyclo-oxygenase inhibitor indomethacin (0.25 mM)
      before treatment with ox-LDL. Aspirin, in a dose- and time-dependent fashion,
      reduced ox-LDL-mediated LOX-1 expression (P<0.01). Ox-LDL also increased MMP-1
      expression and activity, and treatment of HCAECs with aspirin decreased this
      effect (P<0.01). Ox-LDL also enhanced the activity of p38MAPK in HCAECs, and
      aspirin blocked this effect of ox-LDL (P<0.01). Treatment of HCAECs with
      salicylate, but not indomethacin, resulted in a suppression of LOX-1 expression,
      an effect similar to that of aspirin. Importantly, both aspirin and salicylate,
      but not indomethacin, decreased superoxide anion generation in ox-LDL-treated
      HCAECs (P<0.05). CONCLUSION: These observations suggest that aspirin inhibits ox
      LDL-mediated LOX-1 expression and interferes with the effects of ox-LDL in
      intracellular signaling (p38MAPK activation) and subsequent MMP-1 activity. These
      novel effects of aspirin may complement its platelet inhibitory effect in acute
      myocardial ischemia.

PMID- 15485684
TI  - If in left human atrium: a potential contributor to atrial ectopy.
AB  - OBJECTIVE: The left human atrium plays an important role in initiation of atrial
      fibrillation (AF) and the hyperpolarization activated cation current (I(f)) is a
      candidate for contributing to abnormal automaticity. However,
      electrophysiological data concerning I(f) are not available in this cardiac
      region and we therefore investigated I(f) in human left atrial tissue. METHODS:
      Human atrial myocytes were isolated from the left atrial appendage (LAA) and the
      left atrial wall (LAW) obtained from patients undergoing open heart surgery. I(f)
      was measured with the whole-cell patch-clamp technique. RESULTS: I(f) densities
      between -70 and -110 mV were found to be significantly higher in LAA than in LAW
      cells. Furthermore, in the group of LAA cells the half maximal activation
      potential (V(1/2)) was found to be less negative (V(1/2) of -84.3+/-1.9 mV,
      n=14/9) compared to LAW cells (V(1/2) of -97.8+/-2.1 mV, n=28/9). Beta-adrenergic
      receptor stimulation with isoproterenol (1 microM) caused an acceleration of
      current activation and a V(1/2) shift to more positive potentials in cells of
      both regions (LAA: 8.8+/-2.3 mV, n=6/4 and LAW: 8.9+/-2.6 mV, n=6/4). Simulations
      using a mathematical model of the human atrial myocyte demonstrated that I(f) was
      able to induce spontaneous activity in the model at a regular rhythm due to the
      interplay of I(f), Na(+)/Ca(2+) exchange current and Ca(2+) release of the
      sarcoplasmic reticulum (SR). CONCLUSIONS: Our study revealed the presence of I(f)
      in left atrial myocytes and showed that I(f) parameters depend on atrial region.
      I(f) current densities were sufficient to convert the mathematical model of a
      quiescent human atrial cell into a "pacemaker cell". These data support the
      hypothesis of I(f) as a contributor to abnormal automaticity in human atrial
      tissue.

PMID- 15485685
TI  - Can PKA activators rescue Na+ channel function in epicardial border zone cells
      that survive in the infarcted canine heart?
AB  - OBJECTIVE AND METHODS: In this study, we investigated the effects of a PKA
      stimulating cocktail on sodium currents from normal epicardial cells (NZs) and on
      those from cells dispersed from the epicardial zone of the 5-day infarcted canine
      heart (IZs). To do so, we used whole-cell voltage-clamp techniques. RESULTS:
      During superfusion with the PKA activator cocktail, peak sodium current (I(Na))
      density significantly increased by 32+/-5.3% (NZs) and 17+/-5.4% (IZs). However,
      despite this increase, IZ peak I(Na) still was not fully restored to NZ values.
      In both cell types, the density effect was accompanied by a shift in I/I(max)
      curves, as well as a slowing in recovery from inactivation. Inactivation from a
      closed state was accelerated. Furthermore, in the presence of chloroquine, which
      is known to interrupt intracellular vesicular traffic, PKA activator effects to
      augment I(Na) were only partially inhibited in NZs but abolished in IZs. To
      understand whether the phosphorylation status of basal Na(+) channels in the two
      cell groups differed, the effects of okadaic acid and PP2A1 were studied. Results
      suggest that in IZs, Na(+) channels in the basal state are already
      phosphorylated. CONCLUSIONS: PKA stimulation of I(Na) of the remodeled IZ does
      augment current density possibly by augmenting the trafficking of channels to an
      active site on the membrane. However, the resulting I(Na), while partially
      rescued, is not similar to the potentiated I(Na) of NZs. Specific kinetic changes
      also occur with the PKA stimulation of IZs and results with okadaic acid and
      PP2A1 suggest that in their remodeled state, Na(+) channels in IZs are already
      phosphorylated.

PMID- 15485686
TI  - A novel SCN5A mutation manifests as a malignant form of long QT syndrome with
      perinatal onset of tachycardia/bradycardia.
AB  - OBJECTIVE: Congenital long QT syndrome (LQTS) with in utero onset of the rhythm
      disturbances is associated with a poor prognosis. In this study we investigated a
      newborn patient with fetal bradycardia, 2:1 atrioventricular block and
      ventricular tachycardia soon after birth. METHODS: Mutational analysis and DNA
      sequencing were conducted in a newborn. The 2:1 atrioventricular block improved
      to 1:1 conduction only after intravenous lidocaine infusion or a high dose of
      mexiletine, which also controlled the ventricular tachycardia. RESULTS: A novel,
      spontaneous LQTS-3 mutation was identified in the transmembrane segment 6 of
      domain IV of the Na(v)1.5 cardiac sodium channel, with a G-->A substitution at
      codon 1763, which changed a valine (GTG) to a methionine (ATG). The proband was
      heterozygous but the mutation was absent in the parents and the sister.
      Expression of this mutant channel in tsA201 mammalian cells by site-directed
      mutagenesis revealed a persistent tetrodotoxin-sensitive but lidocaine-resistant
      current that was associated with a positive shift of the steady-state
      inactivation curve, steeper activation curve and faster recovery from
      inactivation. We also found a similar electrophysiological profile for the
      neighboring V1764M mutant. But, the other neighboring I1762A mutant had no
      persistent current and was still associated with a positive shift of
      inactivation. CONCLUSIONS: These findings suggest that the Na(v)1.5/V1763M
      channel dysfunction and possible neighboring mutants contribute to a persistent
      inward current due to altered inactivation kinetics and clinically congenital
      LQTS with perinatal onset of arrhythmias that responded to lidocaine and
      mexiletine.

PMID- 15485687
TI  - Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis.
AB  - OBJECTIVE: The responses to bacterial lipopolysaccharide (LPS) damage
      mitochondria by generating oxidative stress within the organelles. We postulated
      that LPS damages heart mitochondrial DNA and protein by oxidation, and that this
      is recovered by oxidative mechanisms of mitochondrial biogenesis. METHODS AND
      RESULTS: Systemic crude E. coli LPS administration decreased mtDNA copy number
      and mtDNA gene transcription in rat heart caused by oxidant deletion of mtDNA.
      The fall in copy number was reflected in proteomic expression of several
      mitochondria-encoded subunits of Complexes I, IV, and V. Recovery of mtDNA copy
      number involved biogenesis as indicated by mitochondrial transcription factor A
      (Tfam) and DNA polymerase-gamma expression. The transcriptional response also
      included nuclear accumulation of peroxisome proliferator-activated receptor-gamma
      co-activator 1 (PGC-1) and mRNA expression for redox-regulated nuclear
      respiratory factors (NRF-1 and -2). CONCLUSIONS: These novel findings disclose a
      duality of reactive oxygen species (ROS) effect in the heart's response to LPS in
      which oxidative mitochondrial damage is opposed by oxidant stimulation of
      biogenesis.

PMID- 15485688
TI  - Attenuation of NF-kappaB signalling in rat cardiomyocytes at birth restricts the
      induction of inflammatory genes.
AB  - OBJECTIVES AND BACKGROUND: The expression of inflammatory genes in the heart
      plays an important role in organ dysfunction. However, the contribution of
      cardiomyocytes to this process, and in particular to the synthesis of high
      concentrations of nitric oxide and prostaglandins, has not been analyzed in
      detail. For this reason, cultured isolated cardiomyocytes were used to evaluate
      the response to pro-inflammatory stimuli. METHODS AND RESULTS: Isolated cultured
      foetal, neonatal, and adult rat cardiomyocytes were stimulated with
      lipopolysaccharide and cytokines, and the expression of nitric oxide synthase-2
      (NOS-2) and cyclooxygenase-2 (COX-2) in these cells was investigated. Only
      cultured foetal cardiomyocytes expressed NOS-2 and COX-2 under these conditions,
      whereas the neonatal counterparts required various days in culture to gain this
      response. Analysis of the NF-kappaB signalling pathway showed an impaired
      activation of IkappaB kinase in response to lipopolysaccharide and cytokines in
      cells maintained in culture for 1 day. These data were confirmed by DNA
      microarray analysis. However, other early signalling pathways, such as the p38
      and Erk MAPKs, were not affected by the time in culture. CONCLUSIONS: Neonatal
      and adult cardiomyocytes are resistant to the expression of pro-inflammatory
      genes due to impairment in the activation of IkappaB kinase, a process that might
      contribute to preventing rapid organ dysfunction in the course of various
      inflammatory pathologies, such as septic shock and myocarditis.

PMID- 15485689
TI  - Inhibition of iNOS augments cardiovascular action of noradrenaline in
      streptozotocin-induced diabetes.
AB  - OBJECTIVE: The aim was to determine if inducible nitric oxide synthase (iNOS)
      contributes to depressed cardiovascular function at the acute phase of
      streptozotocin-induced diabetes. METHODS: Male Wistar rats were injected with
      streptozotocin [60 mg/kg, intravenously (i.v.)] or the vehicle (0.9% NaCl) and
      were studied 3 weeks later. RESULTS: The diabetic and control rats had similar
      mean arterial pressure (MAP) and total peripheral resistance (TPR). Noradrenaline
      (NA) increased in vivo left ventricular contractility (LV +dP/dt), MAP and TPR in
      both groups; however, the responses were markedly less in the diabetic than
      control rats. Acute administration of 1400W (selective inhibitor of iNOS; 3 mg/kg
      followed by 3 mg/kg/h, i.v.) did not alter responses to NA in the control rats,
      but augmented the influence of NA on MAP, TPR and LV +dP/dt in the diabetic rats.
      At this time, reverse transcription-polymerase chain reaction (RT-PCR) products
      (RNA) of iNOS were present in the hearts of the diabetic but not control rats.
      The activity of iNOS was threefold higher in the hearts of the diabetic rats
      relative to the controls, and the increase was inhibited by 1400W. Furthermore,
      immunostaining (proteins) of iNOS and nitrotyrosine (NT; marker of peroxynitrite)
      were identified in the hearts of the diabetic but not control rats. In contrast,
      the RT-PCR products of eNOS, activity of eNOS and immunostaining of eNOS were of
      similar intensity in the hearts of both groups. CONCLUSIONS: Activation of iNOS
      contributes to depressed cardiovascular contractile function to NA at the acute
      phase of streptozotocin-induced diabetes. Selective inhibition of iNOS partially
      restored cardiovascular responses to NA.

PMID- 15485690
TI  - Left ventricular assist device support reverses altered cardiac expression and
      function of natriuretic peptides and receptors in end-stage heart failure.
AB  - OBJECTIVE: Atrial (ANP) and B-type natriuretics peptides (BNP) via their guanylyl
      cyclase-A (GC-A) receptor not only regulate arterial blood pressure and volume
      but also exert local antihypertrophic, antifibrotic and lusitropic effects in the
      heart. To elucidate whether cardiac hypertrophy/insufficiency and reversal is
      associated with changes in the local responsiveness to NPs, we compared the mRNA
      expression of ANP, BNP and receptors and the responsiveness of GC-A to ANP in
      left ventricular tissue obtained from 10 patients with congestive heart failure
      (CHF) before and after hemodynamic unloading by left ventricular assist device
      (LVAD) support. METHODS AND RESULTS: Quantitative "real time" RT-PCR demonstrated
      that the mRNA expression levels of ANP, BNP and the NP-metabolizing NPR-C
      receptor were both markedly increased in human failing hearts. GC-A mRNA
      expression levels were not different from nonfailing hearts, but cGMP production
      by GC-A in response to ANP was nearly abolished. Reversal of cardiomyocyte
      hypertrophy during LVAD support was accompanied by normalization of ANP, BNP and
      NPR-C mRNA levels and a significant recovery of GC-A responsiveness to ANP.
      CONCLUSION: In CHF patients, increased local clearance by NPR-C receptors and
      diminished responsiveness of cardiac GC-A might impair the local antihypertrophic
      effects of natriuretic peptides and contribute to the progression of cardiac
      hypertrophy and insufficiency. Reverse remodeling during LVAD support reverses
      these changes and can thereby recuperate the local protective effects of ANP and
      BNP.

PMID- 15485691
TI  - Protective role of Nd1 in doxorubicin-induced cardiotoxicity.
AB  - OBJECTIVE: The Ndl gene, which encodes a novel kelch family protein, is expressed
      ubiquitously in mouse tissues. In vitro studies suggest that Ndl protein, which
      binds to actin filaments, functions as a cytoskeletal stabilizer. In order to
      elucidate a physiological function of Ndl in vivo, we generated Nd1-deficient
      (Ndl-/-) mice. METHODS: We developed Nd1-/- mice by standard gene targeting
      technique. Cardiac function was studied in wild type and Nd1-/- mice. RESULTS:
      Nd1-/- mice were viable and no gross anatomical abnormality was observed after
      birth. When mouse embryonic fibroblasts were cultured in the presence of
      cytochalasin D or doxorubicin, the number of apoptotic cells in the Nd1-/- cell
      culture was larger that that in the wild-type cell culture. Furthermore, Nd1-/-
      mice were sensitive to doxorubicin-induced cardiotoxicity with increased numbers
      of cardiomyocytes apoptosis. CONCLUSIONS: Although Nd1 is dispensable for normal
      mice development, Nd1 plays a protective role in doxorubicin-induced cardiotoxic
      responses.

PMID- 15485692
TI  - Role of microtubules in ischemic preconditioning against myocardial infarction.
AB  - OBJECTIVE: The role of microtubules in ischemic preconditioning (PC) was
      investigated in isolated perfused rabbit hearts. METHODS: Myocardial infarction
      was induced by 30-min global ischemia and 2-h reperfusion, and infarct size was
      expressed as a percentage of the left ventricle (%IS/LV). Using separate groups
      of rabbits, ventricular biopsies were taken before and after PC for determination
      of protein kinase C (PKC) translocation and p38-mitogen-activated protein kinase
      (p38MAP kinase) activation. To depolymerize microtubules, we used two
      structurally different agents, colchicine (50 microM) and nocodazole (1 microM).
      RESULTS: PC with two cycles of 5-min ischemia/5-min reperfusion significantly
      reduced infarct size from 60.1+/-5.0% to 20.0+/-5.0%. Although neither colchicine
      nor nocodazole modified infarct size in nonpreconditioned hearts, these agents
      abolished the infarct size-limiting effects of PC (%IS/LV=56.1+/-6.0% and 53.5+/
      2.5%, respectively). Colchicine prevented translocation of PKC-epsilon and p38MAP
      kinase activation by PC. PKC translocation by infusion of 1-oleyl-2-acetyl-sn
      glycerol in nonischemic hearts was also prevented by colchicine. CONCLUSION:
      Microtubules play a crucial role in the development of anti-infarct tolerance by
      PC as a mechanism supporting translocation of activated PKC.

PMID- 15485693
TI  - HMG-CoA reductase inhibitors up-regulate anti-aging klotho mRNA via RhoA
      inactivation in IMCD3 cells.
AB  - OBJECTIVE: Klotho is thought to play a critical role in the development of age
      related disorders including arteriosclerosis. Statins may exert vascular
      protective effects, independent of the lowering of plasma cholesterol levels. We
      investigated the impact of statins on mRNA expression of the age-suppressor gene,
      klotho in mIMCD3 cells. METHODS AND RESULTS: Klotho mRNA levels were evaluated
      with real-time RT-PCR. Atorvastatin and pitavastatin increased the expression of
      klotho mRNA in a dose-dependent manner. This stimulatory effect was abolished by
      the addition of mevalonate, GGPP and FPP, essential molecules for isoprenylation
      of the small GTPase Rho. As was the case with the statin treatment, inhibition of
      Rho-kinase by Y27632 up-regulated klotho mRNA. In contrast to the statin
      treatment, stimulation with angiotensin II down-regulated klotho mRNA expression
      without obvious morphological changes. Furthermore, pretreatment with
      atorvastatin blunted the angiotensin II-induced response and ameliorated the
      decrease in klotho mRNA expression towards basal levels. RhoA activity was
      further evaluated by detection of its translocation. Angiotensin II activated
      RhoA, whereas statins potently inactivated RhoA and blocked RhoA activation by
      angiotensin II. CONCLUSION: Statins inactivate the RhoA pathway, resulting in
      over-expression of klotho mRNA, which may contribute to the novel pleiotropic
      effects of statins towards vascular protection.

PMID- 15485694
TI  - Transendothelial exchange of low-density lipoprotein is unaffected by the
      presence of severe atherosclerosis.
AB  - OBJECTIVE: We tested the hypothesis that transendothelial exchange of low-density
      lipoprotein (LDL) is influenced by the presence of severe atherosclerosis; we
      previously found this exchange elevated in diabetes patients. METHODS: By an in
      vivo isotope method, we compared transendothelial LDL exchange in 24 patients
      with angiographically verified coronary atherosclerosis, 11 patients with
      angiographically verified peripheral atherosclerosis, 60 patients with diabetes,
      and in 42 controls. Autologous 131-iodinated LDL ((131)I-LDL) and 125-iodinated
      albumin ((125)I-albumin) were injected intravenously (i.v.), and the 1-h
      fractional escape rates (FER(LDL) and FER(alb)) were taken as indices of
      transendothelial exchange. RESULTS: Patients with coronary or peripheral
      atherosclerosis had FER(LDL) similar to that of controls [4.3 (3.5-5.1) and 3.2
      (2.3-4.1) versus 4.2 (3.7-4.7)%/h; P>0.05], even after adjustment for LDL
      distribution volume (DV(LDL)). In contrast, diabetes patients had significantly
      higher FER(LDL) than controls [5.2 (4.6-5.7) versus 4.2 (3.7-4.7)%/h; P<0.05].
      This difference was even more pronounced after correction for the distribution
      volume of LDL. Compared with controls, FER(alb) was not elevated in patients with
      coronary atherosclerosis, possibly elevated in patients with peripheral
      atherosclerosis, but was elevated in diabetes patients. There was a tight
      positive correlation between FER(LDL) and FER(alb) in all groups of patients and
      controls. CONCLUSION: Transendothelial exchange of low-density lipoprotein is not
      elevated in patients having severe atherosclerosis. This suggests that the
      observed vascular leakiness in diabetes precedes and possibly contributes to
      accelerated atherosclerosis in diabetes.

PMID- 15485695
TI  - Synergistic upregulation of low-density lipoprotein receptor activity by
      tamoxifen and lovastatin.
AB  - OBJECTIVE: To study the mechanism involved in the cholesterol-lowering activity
      of tamoxifen, an estrogen receptor (ER) modulator widely used in breast cancer
      therapy. METHODS AND RESULTS: We used MOLT-4 cells, which do not express estrogen
      receptors and require important amounts of cholesterol for proliferation. We
      firstly confirmed that tamoxifen reduced cholesterol biosynthesis by inhibiting
      sterol Delta(8,7)-isomerase and Delta(24)-reductase activities, which resulted in
      the accumulation of zymosterol. In cells incubated in the presence of low-density
      lipoprotein (LDL) (120 microg cholesterol/ml), tamoxifen stimulated LDL receptor
      activity and expression in a dose-dependent manner, as determined by 1,1'
      dioctadecyl-3,3,3,3'-tetramethylindocarbocyanineperchlorate (DiI)-labeled LDL
      uptake, LDL receptor expression on the cell surface and LDL receptor mRNA levels.
      Furthermore, tamoxifen, but not lovastatin, inhibited the egress of LDL-derived
      cholesterol from lysosomes, as ascertained by filipin staining in both MOLT-4 and
      HepG2 cells. When studied in combination, especially at relatively high LDL
      concentrations in the medium, tamoxifen and lovastatin stimulated LDL receptor
      activity synergistically, which is attributed to the different mechanism of
      action these drugs exhibit. CONCLUSIONS: The present study demonstrates the
      stimulation of the LDL receptor by tamoxifen. These results explain the long
      known hypolipidemic effect of tamoxifen and support its use, or that of other
      intracellular cholesterol trafficking inhibitors, in combination with statins for
      the reduction of plasma LDL cholesterol levels.

PMID- 15485696
TI  - Differential effects of MCP-1 and leptin on collateral flow and arteriogenesis.
AB  - OBJECTIVE: Strategies to therapeutically stimulate collateral artery growth in
      experimental models have been studied intensively in the last decades. However,
      the experimental methods to detect collateral artery growth are discussed
      controversially and vary significantly. We compared different methods in a model
      of arteriogenesis in the rabbit hind limb and determined the effects on
      collateral flow of a known pro-arteriogenic factor, monocyte chemoattractant
      protein-1 (MCP-1), and a cytokine not previously evaluated for its arteriogenic
      efficacy, the adipocytokine leptin. METHODS AND RESULTS: Forty-two New Zealand
      White rabbits received either MCP-1, leptin or PBS after ligation of the right
      femoral artery. The pro-arteriogenic effect of MCP-1 was confirmed by flow
      measurements during reactive hyperemia, as demonstrated by increased flow ratio
      (PBS 0.56+/-0.07 vs. MCP-1 0.77+/-0.06, no unit, p<0.0001), ankle-brachial index
      and microsphere-based conductance measurements (PBS 50.8+/-2.1 vs. MCP-1 225.8+/
      8.8 ml/min/100 mm Hg, p<0.001). Biological activity of leptin on rabbit monocytes
      was shown by a dose dependent increase in Mac-1 expression. In-vivo
      administration of leptin also led to an increase in hyperemic flow and flow ratio
      (leptin 0.69+/-0.03, p<0.05 vs. PBS), but not to an increase in collateral
      conductance (leptin 54.7+/-4.1 ml/min/100 mm Hg, p=ns vs. PBS) or proliferation
      of vascular smooth muscle cells (Ki-67 staining: PBS 24.7+/-3.9%, leptin 22.7%+/
      0.8% (p=ns), MCP-1 32.0+/-1.9% (p<0.01)). Ki-67 mRNA measured by real-time
      polymerase chain reaction increased (8.8+/-3.1-fold, p<0.01) during natural
      arteriogenesis, and was further enhanced (25.5+/-8.1-fold, p<0.005) after
      stimulation with MCP-1. CONCLUSION: MCP-1 and leptin increase collateral flow in
      the rabbit hind limb model. In contrast to MCP-1, leptin does not enhance direct
      markers of vascular proliferation such as collateral conductance under maximal
      vasodilation and proliferation indices. The observed increase in hyperemic
      collateral flow thus most probably can be attributed to the well-documented
      vasodilatory effects of leptin. These data stress the necessity of the use of
      proliferation markers and microsphere-based conductance measurements under
      maximal vasodilation in order to separate effects of substances on vascular
      proliferation from effects on vasodilation.

PMID- 15485697
TI  - Cardiac outflow tract malformations in chick embryos exposed to homocysteine.
AB  - OBJECTIVE: Increased homocysteine concentrations have been associated with
      cardiac outflow tract defects. It has been hypothesized that cardiac neural crest
      cells were the target cells in these malformations. Cardiac neural crest cells
      migrate from the neural tube and contribute to the condensed mesenchyme of the
      aorticopulmonary septum and outflow tract cushions of the heart. The aim of this
      study is to investigate the effects of homocysteine on cardiac neural crest cells
      in relation to heart malformations. METHODS: Homocysteine was injected either
      into the neural tube lumen (30 micromol/l), or into the circulatory system (30 or
      300 micromol/l) of chick embryos. LacZ-retroviral labeling was used to study
      cardiac neural crest cell migratory pathways after exposure to homocysteine.
      RESULTS: Cardiac neural crest cells contributed to the aorticopulmonary septum of
      both control and homocysteine-treated embryos. However, the outflow tract of
      homocysteine-neural tube injected embryos displayed 60% less apoptosis and 25%
      reduced myocardialization. A subarterial ventricular septal defect was observed
      in 83% of the embryos. None of these abnormalities were observed in homcysteine
      circulatory system injected embryos. CONCLUSION: This study demonstrates that
      homocysteine disturbs apoptosis and myocardialization of the outflow tract,
      probably by affecting the cardiac neural crest cells.

PMID- 15485698
TI  - A prospective study of Plasmodium falciparum multiplicity of infection and
      morbidity in Tanzanian children.
AB  - Several studies suggest that in individuals with substantial previous exposure to
      malaria, co-infection with multiple clones of Plasmodium falciparum can protect
      against subsequent clinical malaria attacks. Other studies, mainly of individuals
      with little previous exposure, found the converse relationship. To test whether
      acquisition of such cross-protection tracks the acquisition of clinical immunity
      in general, 610 Tanzanian children aged 0-6 years were enrolled in a nine-month
      prospective study of the risk of morbidity in relation to parasitological status
      and merozoite surface protein 2 genotypes on enrolment. Prevalence of
      parasitaemia and multiplicity of infection increased with age. In the first year
      of life, the incidence of clinical malaria was almost three times higher in
      children with parasites at baseline than in those without. In older children,
      baseline P. falciparum infections appeared to protect against both parasitaemic
      and non-parasitaemic fever episodes. In children aged less than three years,
      baseline multiple infection tended to be associated with higher prospective risk
      of clinical malaria than single infection while in children aged more than three
      years the converse was found, but these effects were not statistically
      significant. These results provide further evidence that relationships between
      asymptomatic malaria infections and clinical malaria change with cumulative
      exposure.

PMID- 15485699
TI  - Monitoring the response to antiretroviral therapy in resource-poor settings: the
      Malawi model.
AB  - With assistance from the Global Fund to Fight AIDS, Tuberculosis and Malaria
      (GFATM), Malawi is scaling-up the delivery of antiretroviral (ARV) therapy to HIV
      positive eligible patients. The country has developed National ARV Treatment
      Guidelines, which emphasize a structured and standardized approach for all
      aspects of ARV delivery, including monitoring and evaluation. Using the
      successful DOTS model adapted by National TB Control Programmes throughout the
      world, Malawi has developed a system of quarterly ARV cohort and cumulative ARV
      quarterly analyses. Thyolo district, in the southern region of Malawi, has been
      using this system since April 2003. This paper describes the standardized ARV
      treatment regimens and the treatment outcomes used in Thyolo to assess the impact
      of treatment, the registration and monitoring systems and how the cohort analyses
      are carried out. Data are presented for case registration and treatment outcome
      for the first quarterly cohort (April to June) and the combined cohorts (April to
      June and July to September). Such quarterly analyses may be useful for districts
      and Ministries of Health in assessing ARV delivery, although the burden of work
      involved in calculating the numbers may become large once ARV delivery systems
      have been established for several years.

PMID- 15485700
TI  - Risk assessment of yellow fever urbanization in Rio de Janeiro, Brazil.
AB  - Yellow fever (YF), an arthropod-borne viral disease, occurs in regions of
      tropical America and Africa. Sylvatic YF is endemic in the north and west of
      Brazil. Urban YF, on the other hand, has not been reported in the country since
      1942. However, the widespread presence of the YF urban vector in Brazil has lead
      to concern about the potential re-emergence of YF in urban centres. Here, we
      assess the risk of YF emergence in the city of Rio de Janeiro, Brazil, by
      estimating the probability of infected individuals arriving from YF-endemic
      areas, and the probability of infective individuals triggering an epidemic. We
      found that the risk of urban YF emergence may reach values as high as 29% during
      the epizootic periods but the precision of the estimate is low.

PMID- 15485701
TI  - Epidemiology and morbidity of Schistosoma mansoni infection in a fishing
      community along Lake Albert in Uganda.
AB  - Schistosoma mansoni infection, associated morbidity and symptoms were studied in
      Piida fishing community at Butiaba, along Lake Albert, Uganda, from November 1996
      to January 1997. The study revealed that S. mansoni is highly endemic with an
      overall prevalence of 72%, a mean intensity of 419.4 eggs per gram (epg) faeces
      (geometric mean for positives only), with 37.8% of males and 33.0% of females
      excreting over 1000 epg. Prevalence and intensity peaked in the 10-14 year old
      age group and decreased with increasing age. Females were less heavily infected
      than males. Differences were also shown between tribes. Diarrhoea and abdominal
      pain were commonly reported in Piida. However, no clear-cut correlation between
      intensity of S. mansoni infection and these conditions could be demonstrated,
      indicating that retrospective questionnaires concerning S. mansoni related
      symptomatology are of limited value. Organomegaly, as assessed by
      ultrasonography, was frequent and hepatomegaly was associated with heavy S.
      mansoni infection. No correlation was demonstrated between splenomegaly and
      infection. This study emphasizes that schistosomiasis mansoni is a major public
      health problem in Piida fishing community and presumably also in many similar
      fishing communities. These observations call for immediate intervention and can
      help in planning long-term strategies for sustainable morbidity control.

PMID- 15485702
TI  - Malaria in camps for internally-displaced persons in Uganda: evaluation of an
      insecticide-treated bednet distribution programme.
AB  - Malaria is a key health problem among displaced populations in malaria-endemic
      areas. Mass distribution of insecticide-treated bednets (ITN) to prevent malaria
      is often carried out in complex emergencies, but there are few data on the
      outcome or operational effectiveness of such programmes. In June 2001, Medecins
      Sans Frontieres completed a mass distribution of ITNs (Permanet) to internally
      displaced persons in Bundibugyo, southwest Uganda, distributing one to four nets
      per household, and aiming to provide coverage for all residents. In July 2002, we
      did a cross-sectional survey using three-stage cluster sampling to evaluate the
      programme. A total of 1245 individuals from 835 households were interviewed. An
      ITN was present in 75.6% (95% CI 72.7-78.5) of the households, but only 56.5%
      (95% CI 52.3-60.4) of individuals were sleeping under an ITN, and nets were often
      damaged. The prevalence of malarial parasitaemia was 11.2% (95% CI 9.4-13.0), and
      was significantly lower in ITN users compared to non-users (9.2% vs. 13.8%,
      relative risk [RR] 0.63, 95% CI 0.46-0.87); ITNs with severe damage remained
      effective (RR for severely damaged net 0.58, 95% CI 0.35-0.98). There was no
      significant difference in haemoglobin concentration between ITN users and non
      users.

PMID- 15485703
TI  - Long-term follow-up of co-infected HIV and Trypanosoma cruzi Brazilian patients.
AB  - Three cases of Trypanosoma cruzi-HIV co-infected haemophiliacs are described.
      Parasitological (xenodiagnosis, haemoculture, PCR) and immunological (CD4+ and
      CD8+ T cell counts, in vitro lymphoproliferative responses) studies were
      performed. Hybridization of isolated parasites with a specific probe confirmed
      the T. cruzi aetiology. We observed that despite the high parasitaemia, no
      clinical or parasitological evidence of T. cruzi reactivation was detected. CD4+
      T cells decreased with time in two patients and the lymphocyte proliferative
      response to T. cruzi was very low in all patients. These data suggest that T.
      cruzi infection may have a long silent course in immunosuppressed HIV patients.
      Therefore, this parasitic infection should be investigated in any AIDS patient
      coming from areas endemic for Chagas' disease.

PMID- 15485704
TI  - Geophagy among pregnant and lactating women in Bondo District, western Kenya.
AB  - Geophagy was studied among 827 pregnant women in western Kenya, during and after
      pregnancy. The women were recruited at a gestational age of 14-24 weeks and
      followed-up to 6 months post-partum. The median age (range) of the women was 23
      years and median parity 2. At recruitment, 378 were eating earth, of which most
      (65%) reported earth-eating before pregnancy. The preferred type of earth eaten
      was soft stone, known locally as odowa (54.2%) and earth from termite mounds
      (42.8%). The prevalence remained high during pregnancy, and then declined to
      34.5% and 29.6% at 3 and 6 months post-partum respectively (P < 0.001). The mean
      daily earth intake was 44.5 g during pregnancy, which declined to 25.5 g during
      lactation (P < 0.001). A random sample of 204 stools was collected from the women
      and analysed for silica content as a tracer for earth-eating. The mean silica
      content was 2.1% of the dry weight of stool. Geophagous women had a higher mean
      silica content than the non-geophagous ones (3.1% vs. 1.4%, P < 0.001). Faecal
      silica and reported geophagy were strongly correlated (P < 0.001).

PMID- 15485705
TI  - Scorpion envenoming in two regions of Colombia: clinical, epidemiological and
      therapeutic aspects.
AB  - To determine clinical and epidemiological features of scorpion stings in two
      departments of Colombia, a descriptive study was performed in the hospitals of 10
      towns from Antioquia (2 256 071 inhabitants) and five from Tolima (630 424
      inhabitants). One hundred and twenty-nine cases were admitted during one year, 51
      in Antioquia, 78 in Tolima and 41 were children less than 15 years old. Most
      stings (70.5%) occurred inside the house; 27.9% were on the hands and 26.4% on
      the feet. The scorpion species involved were Tityus pachyurus (51), Centruroides
      gracilis (31), T. fuehrmanni (29), T. asthenes (7) and Chactas spp. (1). In 10
      cases the scorpion involved was not identified. Systemic envenoming signs (e.g.
      vomiting, tachypnea) were significantly more frequent in children than in adults
      (P < 0.05). Four children had hypertension, but none developed pulmonary oedema.
      One 3-year-old girl, stung by T. asthenes, had acute oedematous pancreatitis.
      Ninety-eight patients had mild envenoming. Moderate (27 patients) and severe
      (four patients) envenoming was significantly more frequent in children than in
      adults (P = 0.003; relative risk = 2.97). A pepsin-digested anti-Centruroides
      spp. antivenom was administered to 19 of 31 patients presenting systemic
      envenoming signs. No adverse reactions to antivenom were observed.

PMID- 15485706
TI  - Case report: Plasmodium ovale infection acquired in Malawi.
AB  - Malaria due to Plasmodium ovale is uncommon outside West Africa. A 37-year-old
      male German who had returned from Malawi four months previously presented in
      September 2003 because of fever recurring every two days. The patient had never
      been to West Africa. Microscopy of stained thick and thin blood films revealed P.
      ovale. This is the first report of a P. ovale infection acquired in Malawi, East
      Africa. Malaria surveillance centres should monitor the possible emergence of
      autochtonous transmission of P. ovale in the area.

PMID- 15485707
TI  - Hepatopathy in complicated falciparum malaria: report from eastern India.
AB  - A prospective study done in 216 children with complicated falciparum malaria
      showed hepatopathy in 33.3% of cases with a higher incidence in children aged
      above five years. Bilirubin and alanine aminotransferase were moderately raised
      in most cases. No significant association with other common complications and no
      higher risk of mortality was observed.

PMID- 15485708
TI  - Comment on: Randomized controlled trial of a traditional preparation of Artemisia
      annua L. (Annual Wormwood) in the treatment of malaria.

PMID- 15485709
TI  - When only the right hemisphere is left: studies in language and communication.
AB  - An adult of above normal intelligence, BL, underwent left hemispherectomy at age
      five, and subsequently graduated from college and has been regularly employed.
      Using standardized neuropsychological instruments, previous extensive testing had
      revealed optimal performance for a hemispherectomized subject. To probe
      communicative abilities in greater detail, and to examine current questions about
      linguistic superiority of the left hemisphere and "crowding" of right hemisphere
      functions, 12 additional protocols were administered. BL performed at normal or
      above on nearly all protocols. However, performance on production of phonemically
      complex words was effortful, and deficits were seen on two tests requiring
      comprehension of linguistic contrasts in prosody (Linguistic Prosody Test) and
      syntax (the Active-Passive Test). These findings support previous claims of
      reduced ability in specific, circumscribed linguistic functions in the left
      hemispherectomized person, and lead to suggestions for further testing of
      communicative competence in individuals with a single intact hemisphere.

PMID- 15485710
TI  - Regular and irregular morphology and its relationship with agrammatism: evidence
      from two Spanish-Catalan bilinguals.
AB  - We report the performance of two aphasic patients in a morphological
      transformation task. Both patients are Spanish-Catalan bilingual speakers who
      were diagnosed with agrammatic Broca's aphasia. In the morphological
      transformation task, the two patients were asked to produce regular and irregular
      verb forms. The patients showed poorer performance with irregular than regular
      morphological transformations in both of their languages. These results are at
      odds with the proposal that agrammatic speech is always or even preponderantly
      associated with poorer performance in processing regular versus irregular verb
      form. Instead, these results support the view that a major component of
      agrammatic production is a deficit in morphosyntactic processing, independently
      of whether this processing ultimately involves regular or irregular forms.

PMID- 15485711
TI  - The role of functional and perceptual attributes: evidence from picture naming in
      dementia.
AB  - We examined the performance of a group of people with moderately severe
      Alzheimer's type dementia on a naming task. We found that functional information
      plays an important role in determining naming performance on both living and non
      living things. Perceptual information may play some role in naming living things.
      We also found some evidence that the semantic category to which an item belongs
      may also have some effect on naming performance. We argue that both the sensory
      functional and domain-specific knowledge hypotheses may be correct: the brain is
      to some organized on taxonomic grounds, while the semantic representations of
      living and non-living things depend differentially on perceptual and functional
      information. These representations can be differentially disrupted by damage to
      modality-specific stores. At a moderate level of severity, dementia causes global
      damage that has the effect of disrupting both the localized taxonomic and the
      modality-specific stores. We discuss the nature of functional information.

PMID- 15485712
TI  - Use of phonological codes for Chinese characters: evidence from processing of
      parafoveal preview when reading sentences.
AB  - The role of phonological coding for character identification was examined with
      the benefit of processing parafoveal characters in eye fixations while reading
      Chinese sentences. In Experiment 1, the orthogonal manipulation of phonological
      and orthographic similarity can separate two types of phonological benefits for
      homophonic previews, according to whether these previews share the same phonetic
      radical with the targets or not. The significant phonological benefits indicate
      that phonological coding is activated early when the character is in the
      parafovea. Experiment 2 manipulated the character's consistency value and found
      that the phonological preview benefits are reliable only when the targets are
      high consistency characters. The results of two experiments suggest that
      phonological computation is rapid and early at both character and radical levels
      for Chinese character identification.

PMID- 15485713
TI  - Functional MRI comparison between reading ideographic and phonographic scripts of
      one language.
AB  - Brain activation during reading of phonographic (Hangul) and ideographic (Hanja)
      words is compared using functional MRI by taking advantage of the bi-scriptal
      system of the Korean language. To examine the psycholinguistic difference, i.e.,
      phonographic vs. ideographic, separately from other differences due to Hanja
      being a secondary script, we made a control comparison between Hangul and the
      English alphabet, another phonographic and secondary script. Interaction analysis
      between the two comparisons revealed that the right fusiform gyrus and adjacent
      temporo-occipital region, among others, seem more specifically involved in
      processing ideographic scripts. On the other hand, regions in bilateral inferior
      parietal lobules were more active with Hangul reading than Hanja. This is
      consistent with the notion that reading the phonographic script may involve the
      assembled phonology route in addition to the addressed lexical route, whereas
      reading the ideographic script may not involve the former.

PMID- 15485714
TI  - Orthographic neighborhood and concreteness effects in the lexical decision task.
AB  - The experiment reported here investigated the sensitivity of concreteness effects
      to orthographic neighborhood density and frequency in the visual lexical decision
      task. The concreteness effect was replicated with a sample of concrete and
      abstract words that were not matched for orthographic neighborhood features and
      in which concrete words turned out to have a higher neighborhood density than
      abstract words. No consistent effect of concreteness was found with a sample of
      concrete and abstract words matched for orthographic neighborhood density and
      frequency and having fewer neighbors and higher-frequency neighbors than the
      words of the first sample. Post hoc analyses of the results showed that
      orthographic neighborhood density was not a nuisance variable producing a
      spurious effect of concreteness but, instead, that the existence of higher
      frequency neighbors constitutes a necessary condition for concreteness effects to
      appear in the lexical decision task. This finding is consistent with the
      hypothesis that semantic information is accessed and used to generate the
      responses in lexical decision when inhibition from orthographic forms delays the
      target word recognition.

PMID- 15485715
TI  - High concentrations of diazepam and nordiazepam in blood of impaired drivers:
      association with age, gender and spectrum of other drugs present.
AB  - A zero-concentration limit for controlled scheduled drugs in the blood of
      motorists was introduced in Sweden in 1999 and the annual number of arrests for
      driving under the influence of drugs (DUID) has since increased eight-fold.
      However, for prescription drugs that might cause impairment (e.g.
      benzodiazepines) additional proof is needed to justify prosecution, such as
      whether the medication was being misused. Over a 2-year period, we found 94 cases
      of DUID in which the concentrations of diazepam in blood was 1.1 microg/g or
      more. Diazepam (D) and nordiazepam (ND) were determined in whole blood by
      capillary gas chromatography with a limit of quantitation of 0.05 microg/g for
      each compound. The mean (median) and maximum concentrations of D were 2.0
      microg/g (1.7 microg/g) and 7.8 microg/g and the corresponding ND concentrations
      were 1.5 microg/g (1.0 microg/g) and 7.6 microg/g, respectively. The
      concentration of D in blood exceeded 2 microg/g in 21% of cases and was over 3.0
      microg/g in 11% of cases. D and ND were the only drugs present in eight cases
      (seven men and one women) and in another five cases ethanol was present at
      concentrations ranging from 0.81 to 1.98 mg/g. Polydrug use was very common in
      these DUID suspects and D and ND coexisted with amphetamine in 20% of cases,
      tetrahydrocannabinol in 18% of cases and with both these illicit drugs in 12% of
      cases. The next most prevalent drug combination was D, ND and morphine (mostly
      derived from heroin), seen in 13% of cases. Other psychoactive prescription drugs
      were identified in blood including alprazolam, flunitrazepam, oxazepam, zolpidem
      and zopiclone. This case series of DUID suspects demonstrate the high frequency
      of polydrug use showing preference for illicit drugs like amphetamine, cannabis
      and heroin, in that order. Furthermore, Swedish traffic delinquents frequently
      overdose with prescription drugs as exemplified here by unusually high
      concentrations of D and its active metabolite ND.

PMID- 15485716
TI  - Forensic analysis of carbohydrate-deficient transferrin (CDT): implementation of
      a screening and confirmatory analysis concept is hampered by the lack of CDT
      isoform standards.
AB  - The aim of the study was to test combinations of commercially available
      carbohydrate-deficient transferrin (CDT) assays for their usefulness as screening
      and confirmatory CDT analysis systems. A set of 292 serum samples from routine
      CDT analysis was analyzed by two assays based on anion-exchanger microcolumn CDT
      and non-CDT fractionation followed by a turbidimetric immunoassay (ChronAlcoI.D.
      and %CDT TIA) and a high-performance liquid chromatography with on-line sample
      preparation (ClinRep CDT on-line). The CDT analysis results were divided into
      four groups based on the test-specific borderlines of the compared methods: NN
      with negative CDT results by both tests, PN with positive screening but negative
      confirmation results, NP with negative screening and positive confirmation
      results, and PP with positive results by both tests. Regardless of the test
      combination and whether applying the lower or upper limits of the borderlines,
      approximately one-third of contradictory (positive screening and negative
      confirmation or vice versa corresponding to groups PN and NP) were obtained. This
      was not due to analytical outliers (only 6 of 292 serum samples). Indeed,
      parametric and non-parametric ANOVA analysis pointed to different calibrations
      and/or recoveries of the three CDT assays. Our data give again evidence for the
      urgent need of an international CDT isoform standard material. At this time, we
      cannot recommend a combination of the three tests for screening and confirmatory
      analysis in forensic CDT testing.

PMID- 15485717
TI  - Ethanol formation in unadulterated postmortem tissues.
AB  - During the investigation of aviation accidents, postmortem samples obtained from
      fatal accident victims are submitted to the FAA's Civil Aerospace Medical
      Institute (CAMI) for toxicological analysis. During toxicological evaluations,
      ethanol analysis is performed on all cases. Many species of bacteria, yeast, and
      fungi have the ability to produce ethanol and other volatile organic compounds in
      postmortem specimens. The potential for postmortem ethanol formation complicates
      the interpretation of ethanol-positive results from accident victims. Therefore,
      the prevention of ethanol formation at all steps following specimen collection is
      a priority. Sodium fluoride is the most commonly used preservative for postmortem
      specimens. Several studies have been published detailing the effectiveness of
      sodium fluoride for the prevention of ethanol formation in blood and urine
      specimens; however, our laboratory receives blood or urine in approximately 70%
      of cases. Thus, we frequently rely on tissue specimens for ethanol analysis. The
      postmortem tissue specimens received by our laboratory have generally been
      subjected to severe trauma and may have been exposed to numerous microbial
      species capable of ethanol production. With this in mind, we designed an
      experiment utilizing unadulterated tissue specimens obtained from aviation
      accident victims to determine the effectiveness of sodium fluoride at various
      storage temperatures for the prevention of microbial ethanol formation. We found
      that without preservative, specimens stored at 4 degrees C for 96 h showed an
      increase in ethanol concentration ranging from 22 to 75 mg/hg (average 42 +/- 15
      mg/hg). At 25 degrees C, these same specimens showed an increase ranging from 19
      to 84 mg/hg (average 45 +/- 22 mg/hg). With the addition of 1.00% sodium
      fluoride, there was no significant increase in ethanol concentration at either
      temperature.

PMID- 15485718
TI  - A study of sexual variation in Indian femur.
AB  - Assessment of sex from femoral dimensions have been tried before in several
      populations. Studies conducted so far have demonstrated that populations differ
      from one another in size and proportion. Therefore, the discriminant formulae
      developed for determining sex for one population group cannot be applied on
      another. As to date no detailed study of femur on the subject has been reported
      from India, an attempt has been made in the present study to examine the sexual
      dimorphism in femur of Indian origin using 124 femora from central India. Eleven
      standard dimensions were measured on the bones. The data were analysed using
      discriminant function procedures and the results of different measurements are
      reported independently and in various combinations. Maximum head diameter alone
      could correctly assign sex to 92.5% of males and 95.5% of females. Evaluation of
      the discriminating ability of the variables selected in stepwise analysis are
      then conducted using cross validation procedure. To understand the population
      variation, the discriminant formula derived from Thai, Chinese, South African
      white, American black and white were applied on the present sample. The
      comparison indicated that Indians have very different dimension from South
      African whites and American whites. Their dimensions are more closer to Thais and
      Chinese but in no way identical to them.

PMID- 15485719
TI  - Deaths due to hunger strike: post-mortem findings.
AB  - Hunger strike is described as voluntary refusal of food and/or fluids. Prolonged
      starvation may produce many adverse events including even death in rare
      circumstances. Here, we present three fatal cases (all males, 25-38 years) died
      from hunger strike. In all corpses, obvious muscle wasting with reduced
      subcutaneous and internal fat deposits, and atrophy in some organs were
      demonstrated at autopsy. The extraordinary long starvation period before death
      could presumably be linked to the thiamine uptake in this period, which had been
      discontinued by all subjects before the death occurred. Prolonged caloric
      deficiency with subsequent complications such as multiple organ failure, severe
      sepsis and ventricular fibrillation could account as major causes of death in
      these subjects. The competence of the physicians working with hunger strikers
      about the processes and potential problems is of great importance since they have
      to acknowledge about them to their patients.

PMID- 15485720
TI  - Hair analysis for fenfluramine and norfenfluramine as biomarkers for N
      nitrosofenfluramine ingestion.
AB  - In this paper, a high performance liquid chromatographic method with fluorescence
      detection (HPLC-FL) for the determination of fenfluramine (Fen) and
      norfenfluramine (Norf) in human hair as biomarker metabolites of N
      nitrosofenfluramine (N-Fen) is described. Washed and cut hair segments were
      extracted by ultrasonication for 1h at room temperature in methanol. The extract
      was evaporated and applied for derivatization with the fluorescent reagent 4-(4,5
      diphenyl-1H-imidazol-2-yl)benzoyl chloride (DIB-Cl). An HPLC-FL analysis was
      performed using an ODS column with mobile phase composition of acetonitrile and
      water (65:35, v/v) and monitored at 430 nm (excitation 325 nm). The method was
      sensitive with detection limits of 36 and 16 pg/mg hair for Fen and Norf,
      respectively. The linearity was assessed in the range 0.036-144 ng/mg for Fen and
      0.016-127 ng/mg for Norf with correlation coefficients larger than 0.999. The
      method was successfully used for the segmental determination of Fen and Norf in
      hair samples obtained from hospitalized patients diagnosed with hepatotoxicity
      and suspected to ingest N-Fen. Both Fen and Norf could be detected in these
      patients' hair samples in the ranges 43-1389 pg/mg for Fen and 18-680 pg/mg for
      Norf and the results showed that the patients might ingest N-Fen for a period of
      not less than 5 months. As well, the method was applied for the determination of
      Fen and Norf in rats that possess pigmented and non-pigmented hair after an
      intraperitoneal administration of Fen. Both compounds were determined in black as
      well as in white hair.

PMID- 15485721
TI  - A fatal overdose of the ergot derivative cabergoline.
AB  - A 79-year-old woman, with Parkinson's disease treated with cabergoline, was
      admitted to a hospital due to jaundice and weakness. She was found confused,
      absent minded, and died after 2 weeks. Autopsy showed an extrahepatic bile duct
      adenocarcinoma with spread to the gall bladder, the liver, and regional
      lymphnodes. While cleaning the hospital bed after her death, the nurses found
      several tablets hidden in the bed. Biological samples obtained at the autopsy
      were screened for common drugs and narcotics. Several drugs such as
      buprenorphine, codeine, paracetamol, and propranolol were detected in the blood
      at therapeutic levels. A method to determine cabergoline in whole blood and other
      forensic matrices was developed, and further investigations determined
      cabergoline concentrations in whole blood and liver tissue of 94 and 3100
      microg/kg, respectively. The blood concentration was 100 times above the
      therapeutic level reported on cabergoline in plasma and in combination with her
      symptoms, suggest she took a fatal overdose of cabergoline.

PMID- 15485722
TI  - Genetic polymorphism at nine STR loci in two ethnic groups of China.
AB  - Genotype polymorphism studies at nine short tandem repeat (STR) loci (D3S1358,
      FGA, TH01, D7S820, VWA, CSF1PO, D5S818, D13S317, TPOX) were carried out in two
      Ethnic Groups (Tu, Sala) living in Qinhai, a North-West province of China. All
      loci were in accordance with Hardy-Weinberg equilibrium (P = 0.05).

PMID- 15485723
TI  - Genetic analysis of 13 STR loci in the population from the State of Pernambuco,
      northeast Brazil.
AB  - Allele frequencies for 13 short tandem repeats (STR) loci obtained from a sample
      of 546 unrelated individuals from the State of Pernambuco, northeast Brazil, were
      studied. This population represents a trihybrid population composed of
      individuals presenting an admixture of Caucasian, African, and Native American.
      In the present study, the distributions of the genotypes in the evaluated loci
      CSF1PO, TH01, TPOX, F13A1, FESFPS, vWA, D16S539, D7S820, D13S317, D18S51, D21S11,
      D8S1179, FGA are in Hardy-Weinberg equilibrium. These loci were studied together
      with the Amel locus to perform the CODIS systems used in the USA. The calculated
      forensic parameters showed that the loci are useful for the solution of forensic
      problems in the Brazilian northeast region.

PMID- 15485724
TI  - Y chromosome haplotypes in Albanian population from Kosovo.
AB  - Eight Y chromosome short tandem repeat (STR) polymorphisms (DYS19, DYS385,
      DYS389I, DYS389II, DYS390, DYS391, DYS392, and DYS393) were analyzed in the
      sample of 117 unrelated Albanian males living in Kosovo. A general STR allelic
      frequency pattern in the Albanian population from Kosovo corresponds to other
      European populations. Fourty six haplotypes were observed in single copy. The
      most frequent haplotypes were (DYS19-DYS385-DYS389I-DYS389II-DYS390-DYS391-DYS392
      DYS393) 14-11/11-13-29-24-11-13-13 (10.26%), 14-14/17-12-28-24-10-11-12 (9.40%),
      13-16/18-13-30-24-10-11-13 (9.40%), and 14-17/17-13-31-24-10-11-13 (9.40%).

PMID- 15485725
TI  - Population data on the X chromosome short tandem repeat loci DXS10011, DXS101,
      DXS6789, DXS7132, DXS8377, and DXS9895 in Taiwan.
AB  - X chromosome linked short tandem repeat (STR) are powerful auxiliary systems to
      genomic STR, they are helpful for differentiating if two women have the same
      father directly, avoiding some of the ambiguity generated from sibship
      estimation. This report contains the results of population studies on the X
      chromosome STR DXS10011, DXS101, DXS6789, DXS7132, DXS8377 and DXS9895 carried
      out in Taiwan. The common alleles of each locus were sequenced and used in a
      control ladder to type unknown samples. The numbers of unrelated individuals were
      273 (female 92 and male 181) for DXS10011 locus, 448 (female 135 and male 313)
      for DXS101 locus, 447 (female 135 and male 312) for DXS6789 locus, 414 (female
      119 and male 295) for DXS7132 locus, 450 (female 135 and male 315) for DXS8377
      locus and 413 (female 120 and male 293) for DXS9895 locus. These STR
      polymorphisms will be a useful marker for parentage testing especially when
      disputed blood relative is female.

PMID- 15485726
TI  - Estrogens and breast cancer: does timing really matter?

PMID- 15485727
TI  - Breast cancer: critical data analysis concludes that estrogens are not the cause,
      however lifestyle changes can alter risk rapidly.
AB  - BACKGROUND: The theory that estrogens are causally associated with increased risk
      of breast cancer and the question of whether lifetime cumulative exposure is
      necessary are critically reviewed. METHODS: Systematic search was made of
      published epidemiological and clinical data relating to estrogen concentrations
      at different times and situations, and of breast cancer incidence with age and
      after lifestyle changes. RESULTS: Breast cancer incidence increases with age,
      although the rate of increase slows. Reproductive factors are known to affect
      risk, but data that do not fit the theory of estrogen causation include low
      estradiol levels and decline of estrogen excretion postmenopausally, rates in HRT
      takers, absence of increased rate during or after pregnancy, and breast cancer in
      men. Breast cancer risk can be altered by external factors within a few years, as
      shown by studies in both Norway and England during World War II, by changing
      rates in migrant populations, and by the effect on rates of recent adiposity.
      CONCLUSIONS: It is probable that estrogens act as promoters rather than being
      directly causal. Even as promoters, lifetime exposure to estrogens is not
      necessary. The cause is most probably a lifestyle factor, changes in which can
      rapidly alter risk. This has important implications in the search for a causative
      factor.

PMID- 15485728
TI  - Telephone reminders are effective in recruiting nonresponding patients to
      randomized controlled trials.
AB  - OBJECTIVE: Studies investigating means of recruiting participants to randomized
      controlled trials (RCTs) are sparse. We investigated the effects of telephone
      reminders as a recruitment strategy. STUDY DESIGN AND SETTING: Sick-listed
      employees received a written invitation to participate in a study comparing
      standard treatments with a solution-focused follow-up and were randomly allocated
      to an intervention or control group (n=703). Those who did not respond within 2
      weeks received either 'no reminder' (n=242) or 'attempted telephone reminder'
      (n=256). Outcome was enrollment to the RCT. RESULTS: An intention to recruit
      analysis revealed no significant differences between the groups (P=.229). An
      intention to phone analysis among nonresponders revealed significant differences
      between 'no reminder' (recruited 4.5%) and 'attempted telephone reminder'
      (recruited 12.1%) (P=.003, odds ratio 2.89, 95% confidence interval [CI] 1.42
      5.90). An analysis of numbers needed to phone showed that to recruit one more
      person in this group of nonresponders, we needed to phone 13 persons (95% CI=8
      33). CONCLUSION: Systematic use of telephone calls can increase the recruitment
      rate among nonresponders in RCTs.

PMID- 15485729
TI  - Prepayment was superior to postpayment cash incentives in a randomized postal
      survey among physicians.
AB  - OBJECTIVE: Improving response rates, particularly among physicians, is important
      to minimize nonresponder bias and increase the effective sample size in
      epidemiologic research. We conducted a randomized trial to examine the impact of
      prepayment vs. postpayment incentives on response rates. STUDY DESIGN AND
      SETTING: Self-completion postal questionnaires were mailed to 949 physicians who
      were respondents to an earlier survey and representative of the general physician
      population in Hong Kong. These physicians were randomly allocated to receive a HK
      dollar 20 cash prepayment incentive that accompanied the survey (n=474) or a
      postpayment reward of the same amount on receipt of the completed questionnaire
      (n=475). RESULTS: The final prepayment response rate was 82.9%, compared with
      72.5% in the postpayment arm (P < .001). Of the eight alternative incentive and
      follow-up strategies evaluated, three lie on the efficiency frontier (i.e., not
      dominated), including postpayment with three mailings at HK dollar 42.7,
      prepayment with three mailings at HK dollar 66.5 and prepayment with three
      mailings and telephone follow-up at HK dollar 112.1 per responder recruited (US
      dollar 1=HK dollar 7.8). CONCLUSION: The findings demonstrate that prepayment
      cash incentives are superior to postpayment of the equivalent amount in improving
      response rates among a representative sample of Hong Kong physicians. Further
      research should concentrate on confirming the generalizability of these findings
      in other health care occupation groups and settings.

PMID- 15485730
TI  - Patterns of intra-cluster correlation from primary care research to inform study
      design and analysis.
AB  - OBJECTIVE: To provide information concerning the magnitude of the intraclass
      correlation coefficient (ICC) for cluster-based studies set in primary care.
      STUDY DESIGN AND SETTING: Reanalysis of data from 31 cluster-based studies in
      primary care to estimate intraclass correlation coefficients from random effects
      models using maximum likelihood estimation. RESULTS: ICCs were estimated for
      1,039 variables. The median ICC was 0.010 (interquartile range [IQR] 0 to 0.032,
      range 0 to 0.840). After adjusting for individual- and cluster-level
      characteristics, the median ICC was 0.005 (IQR 0 to 0.021). A given measure
      showed widely varying ICC estimates in different datasets. In six datasets, the
      ICCs for SF-36 physical functioning scale ranged from 0.001 to 0.055 and for SF
      36 general health from 0 to 0.072. In four datasets, the ICC for systolic blood
      pressure ranged from 0 to 0.052 and for diastolic blood pressure from 0 to 0.108.
      CONCLUSION: The precise magnitude of between-cluster variation for a given
      measure can rarely be estimated in advance. Studies should be designed with
      reference to the overall distribution of ICCs and with attention to features that
      increase efficiency.

PMID- 15485731
TI  - Advances in risk-benefit evaluation using probabilistic simulation methods: an
      application to the prophylaxis of deep vein thrombosis.
AB  - OBJECTIVE: To demonstrate the use of probabilistic simulation modeling to
      estimate the joint density of therapeutic risks and benefits. Published data are
      used to introduce the risk-benefit acceptability curve as a novel method of
      illustrating risk-benefit analysis. STUDY DESIGN AND SETTING: Using published
      data, we performed a second-order Monte Carlo simulation to estimate the joint
      density of major bleeding and deep vein thrombosis (DVT) secondary to enoxaparin
      or unfractionated heparin. Within a Bayesian framework, beta-distributions for
      the probabilities of experiencing a DVT and major bleed were derived from the
      clinical trial, and incremental probabilities were calculated. RESULTS: The
      incremental risk-benefit pairs from 3,000 simulations are presented on a risk
      benefit plane. To accommodate different risk preferences, the results are also
      illustrated using a risk-benefit acceptability curve, which incorporates
      different risk-benefit acceptability thresholds (mu), or the number of major
      bleeds one is willing to accept in order to avert one DVT. Finally, a net-benefit
      curve is used to illustrate the risk-benefit ratio and the derivation of 95%
      confidence intervals around the ratio. CONCLUSION: Modern simulation methods
      permit the estimation of the joint density of risks and benefits with their
      associated uncertainty, and within a Bayesian framework, facilitate the
      estimation of the probability that a therapy is net-beneficial over different
      preference thresholds for risk-benefit trade-offs.

PMID- 15485732
TI  - Tumor measurements on computed tomographic images of non-small cell lung cancer
      were similar among cancer professionals from different specialties.
AB  - OBJECTIVE: In this study, we addressed the influence of the observer's background
      and experience on the accuracy of imaging-based tumor measurements. The
      consistency of measures with Response Evaluation Criteria in Solid Tumors
      (RECIST) vs. WHO criteria is also reported. STUDY DESIGN AND SETTING: Twenty-five
      observers (five radiologists, five thoracic surgeons, five radiotherapists, five
      pulmonologists, and five medical oncologists) were asked to measure three lesions
      on selected serial chest computed tomographic images from three non-small cell
      lung cancer patients treated with chemotherapy. The observers were asked to
      measure the longest diameter (RECIST), along with its perpendicular diameter (WHO
      criteria). Measurements by radiologists were used as reference values. RESULTS:
      There was no significant difference in the accuracy of measurements among the
      different groups. The highest intraobserver consistency was achieved by
      radiologists. Neither familiarity with measuring tumor lesions nor years since
      the MD degree correlated with measurement accuracy. A comparison of RECIST and
      WHO criteria showed consistent response ratings (kappa=.74, CI 95%=.57-.91).
      CONCLUSION: Measurements of selected lesions were consistent among specialists,
      suggesting that assessment of tumor response is reliable even when it is not done
      by radiologists.

PMID- 15485733
TI  - A children's acute respiratory illness scale (CARIFS) predicted functional
      severity and family burden.
AB  - OBJECTIVE: The Canadian Acute Respiratory Illness and Flu Scale (CARIFS) was
      developed to measure illness severity in children with acute respiratory
      infection. The objective of this study was to evaluate its performance in a
      European primary care setting. STUDY DESIGN AND SETTING: 178 children (median age
      3 years) with cough and fever were recruited in UK general practice. Perceived
      severity of illness at recruitment was recorded by parents, doctors, and nurses.
      Parents also completed an illness diary, including the CARIF scale, until their
      child had recovered. In-depth interviews were conducted with 24 parents. RESULTS:
      Parents found CARIFS relatively easy and quick to complete (78% of parents
      returned a fully completed diary covering the duration of the illness), internal
      consistency was high (minimum item correlation with total score 0.22; overall
      Cronbach's alpha statistic 0.85), and responsiveness to improvement in health was
      good (observed effect size of 0.45 at 8 h). At presentation, however, neither the
      overall CARIFS score nor the clinical element of the score correlated with
      physician assessment of clinical severity. CONCLUSION: Of the three recognized
      domains of illness severity, CARIFS appears to be a good and valid measure of
      functional severity and burden of illness to the parent but it may not be a good
      measure of physiological severity.

PMID- 15485734
TI  - Validity of conjoint analysis to study clinical decision making in elderly
      patients with aortic stenosis.
AB  - OBJECTIVE: Written case simulations are increasingly being used to investigate
      clinical decision making. Our study was designed to determine the validity of
      written case simulations within a conjoint analysis approach. STUDY DESIGN AND
      SETTING: We developed a series of 32 written case simulations that differed with
      respect to nine clinical characteristics. These case simulations represented
      elderly patients with aortic stenosis. The clinical characteristics varied
      according to a fractional factorial design. We analyzed retrospectively all
      consecutive patients of 70 years of age or older with an aortic stenosis in three
      university hospitals. RESULTS: 34 cardiologists from three Dutch hospitals gave
      their treatment advice to each of these case simulations on a six-point scale
      (ranging from 'certainly no' to 'certainly yes' to surgical treatment). We
      compared the influence that the clinical characteristics had on the responses to
      these case simulations with their influence on the actual treatment decision for
      147 actual patients in the same three hospitals. We found a strong agreement.
      This agreement was only slightly affected by the cut-off value used to
      dichotomize the treatment advice into a recommendation in favor of or against
      surgical treatment. CONCLUSION: Written case simulations reflect well how
      clinicians are influenced by specific clinical characteristics of their patients.

PMID- 15485735
TI  - Screening mammography was used more, and more frequently, by longer than shorter
      term Medicaid enrollees.
AB  - OBJECTIVE: Recent studies have shown that timing and length of enrollment (LOE)
      in Medicaid in relation to cancer diagnosis are associated with stage of breast
      cancer among Medicaid beneficiaries. Whether LOE in Medicaid is also associated
      with the use of screening mammography (USM) is unclear, however. The objective
      was to determine whether USM among Medicaid beneficiaries is associated with LOE
      in Medicaid. STUDY DESIGN AND SETTING: The study used Ohio Medicaid enrollment
      and claims files, and a cohort approach to estimate USM during the 8-year study
      period. USM was assessed through (a) the proportion of women receiving screening
      mammography, and (b) the frequency of screening mammography exams. This study
      used women 40-64 years of age enrolled in Ohio Medicaid during 1992-1999
      (n=140,592). RESULTS: The proportion of women receiving screening mammography
      increased significantly with each additional year of LOE [adjusted odds ratio
      (AOR): 1.59, 95% confidence interval (95% CI): 1.57-1.60], and was higher among
      women presenting comorbid conditions (AOR: 3.05; 95% CI: 2.90-3.20). The mean
      number of annual mammography exams increased from 0.08 among women with LOE < or
      = 12 months, to 0.26 among women with LOE > or = 7 years. CONCLUSION: Both LOE
      and comorbid conditions are independently, significantly, and positively
      associated with USM, although their interactive effect relative to USM needs to
      be studied further. These findings have important implications in the methods
      employed to study use of cancer screening and other preventive services by
      Medicaid beneficiaries, as well as in Medicaid policy analysis and program
      management.

PMID- 15485736
TI  - A prospective study found impaired left ventricular function predicted job
      retirement after acute myocardial infarction.
AB  - OBJECTIVE: Impaired left ventricular function is associated with poor prognosis
      after acute myocardial infarction (MI). It might be hypothesized that impaired
      left ventricular function would also affect work outcome; however, no existing
      data address this hypothesis. This study examines whether reduced left
      ventricular systolic function had any influence on the 4-year retirement rate
      after acute MI. STUDY DESIGN AND SETTING: We conducted a prospective study
      including 242 working-active patients with MI. Left ventricular ejection fraction
      (LVEF) was estimated by echocardiography during hospital admission. Data about
      work outcome after 4 years were collected by telephone interviews. RESULTS: Fifty
      percent were retired by the end of follow-up. Moderately or severely reduced LVEF
      (35%) increased the risk of retirement almost twofold (risk ratio RR=1.8, 95%
      confidence interval CI=1.3-2.5). After adjusting for confounding factors, reduced
      LVEF was an independent predictor of retirement. Based on a stratified analysis,
      being female (RR=3.90, 95% CI=1.18-12.62) or having heavy physical job demands
      (RR=3.83, 95% CI=1.02-14.30) had a more pronounced impact on retirement for
      patients with LVEF 35%, compared with patients with better left ventricular
      function. CONCLUSION: We conclude that impaired left ventricular systolic
      function is a prognostic determinant of retirement from the job market after
      acute MI.

PMID- 15485737
TI  - Tissue plasminogen activator was cost-effective compared to streptokinase in only
      selected patients with acute myocardial infarction.
AB  - OBJECTIVE: We sought to explore the patient-specific cost-effectiveness in a
      community-based sample for a therapy for which the average cost-effectiveness in
      a clinical trial has been well-described. STUDY DESIGN AND SETTING: Based on a
      validated multivariate model, we generated predictions of the effectiveness and
      cost-effectiveness of t-PA compared to streptokinase on 921 consecutive patients
      who received thrombolytic therapy for acute myocardial infarction. RESULTS: The
      average cost-effectiveness of t-PA was US dollar 40,140 per life-year saved. For
      the quartile of patients most likely to benefit, the incremental cost
      effectiveness of t-PA was US dollar 15,396. However, only 44% of patients who
      received thrombolytic therapy had an estimated cost-effectiveness ratio below US
      dollar 50,000 per year of life saved; the ratio was greater than US dollar
      100,000 in 37% of treated patients. Patients in the lowest quartile of expected
      benefit are, overall, more likely to be harmed than to benefit from t-PA.
      CONCLUSION: Compared to the pattern of thrombolytic agent choice observed,
      targeting t-PA to the half of patients most likely to benefit could save 247
      lives and US dollar 174 million nationally per year.

PMID- 15485738
TI  - A cohort study found racial differences in dental insurance, utilization, and the
      effect of care on quality of life.
AB  - OBJECTIVE: To describe racial differences in receipt of dental services and
      dental insurance; and to determine the effectiveness of specific dental services
      in facilitating recovery in symptom-specific and race-specific subgroups. STUDY
      DESIGN AND SETTING: Using a restricted cohort analytic method, Florida Dental
      Care Study prospective cohort data were used to quantify associations between
      dental service use and the quality of life measure, "recovery" from oral
      disadvantage due to functional limitation. RESULTS: Non-Hispanic Whites (NHW)
      were more likely to have a dental visit [odds ratio (OR); 95% confidence
      interval: 3.5; 2.2-5.3], corrective treatment (OR=2.1; 1.3-3.3), caps (OR=28.8;
      6.6-126.4), and dental insurance coverage for caps (OR=2.9; 1.4-5.9). After
      adjusting for other covariates: (1) among NHW with severe gum disease, those
      receiving extractions were more likely to recover (OR=7.8; 1.0-59.1), but those
      receiving caps were less likely to recover (OR=0.1; 0.01-0.6); (2) among Non
      Hispanic Blacks (NHB) with a sensitive tooth, those receiving corrective
      treatment (OR=3.2; 1.2-8.8) or extractions (OR=3.8; 1.3-11.2) were more likely to
      recover; (3) among NHB with tooth disease, those receiving corrective treatment
      (OR=2.3; 1.0-5.0) and extractions (OR=2.8; 1.2-6.5) were more likely to recover.
      CONCLUSION: There were racial differences in dental insurance, in the receipt of
      dental services and in the effectiveness of dental services in improving oral
      health-related quality of life.

PMID- 15485739
TI  - A prospective study linked both alcohol and tobacco to Dupuytren's disease.
AB  - OBJECTIVE: To address the role of alcohol intake and tobacco smoking and the
      combination of the two on subsequent risk of Dupuytren's disease. STUDY DESIGN
      AND SETTING: Cohort study of 7,254 subjects enrolled in the Copenhagen City Heart
      Study (1981-1983). Both self-reported information on lifestyle and objective
      measures at the baseline examination were linked to presence of Dupuytren's
      disease at a subsequent examination (1991-1994) using multivariate logistic
      regression analysis. RESULTS: A total of 772 subjects had signs of Dupuytren's
      disease at follow-up. After adjustment for age, sex, educational level, diabetes,
      and either alcohol or tobacco consumption, respectively, odds ratios for having
      the disease increased in a dose-dependent manner with increasing levels of
      alcohol or tobacco intake; however, there was no statistical interaction between
      heavy smoking and heavy drinking. CONCLUSION: Alcohol intake and tobacco smoking
      are independently associated with increased risk of Dupuytren's disease, and the
      combination of the two conveys a very large risk.

PMID- 15485740
TI  - The clinical diagnosis of acute rhinosinusitis and its therapeutic consequences.

PMID- 15485742
TI  - Should we consider Embase in Latin America?

PMID- 15485744
TI  - Sample size for diagnostic accuracy studies.

PMID- 15485746
TI  - Reduced sympathoneural responses to the cold pressor test in individuals with
      essential hypertension and in those genetically predisposed to hypertension. No
      support for the "pressor reactor" hypothesis of hypertension development.
AB  - BACKGROUND: The aim of this study was to examine the influences of genetic
      predisposition to hypertension and of age on the sympathetic nervous system
      response to the cold pressor test (CPT). METHODS: A total of 32 young subjects
      (aged 27 +/- 2 years) were studied: 11 normotensive subjects without a family
      history of hypertension (FH), 14 normotensive subjects with a strong family
      history of hypertension (FH+), and eight hypertensive subjects. In addition, 21
      older subjects (aged 53 +/- 2 years) were studied: 13 hypertensive and eight
      normotensive subjects. Blood pressure (BP), heart rate (HR), and muscle
      sympathetic nerve activity (MSNA) were recorded at rest and during a 2-min period
      of a CPT. RESULTS: Both young and older hypertensive subjects had higher resting
      MSNA than did the normotensive ones (47 +/- 7 v 29 +/- 4 bursts per 100
      heartbeats (P < .05) and 66 +/- 4 v 40 +/- 7 bursts per 100 heartbeats (P < .01),
      respectively). The CPT resulted in HR increases of similar magnitude in all
      groups of patients. The FH+ group displayed slightly less increase in systolic BP
      than that of the FH- group (P < .05). The MSNA increased to a far greater degree
      in FH- (103%) than in FH+ (32%) and in young hypertensive patients (12%) (P <
      .05). Similarly, MSNA change with the CPT was greater in older normotensive
      subjects than in older hypertensive patients (61% v 12%, P < .05). CONCLUSIONS:
      Our results show that a CPT induces sympathetic responses that are subnormal in
      hypertensive patients and those with a family history of hypertension,
      highlighting the importance of genetic factors in determining the sympathetic
      nervous reactivity to CPT.

PMID- 15485747
TI  - Out-of-office blood pressure in children and adolescents: disparate findings by
      using home or ambulatory monitoring.
AB  - BACKGROUND: The validity of home blood pressure (HBP) measurements in children
      has not been evaluated, although in clinical practice such measurements are being
      used. This study compares HBP, with clinic (CBP) and daytime ambulatory blood
      pressure (ABP) in children and adolescents. METHODS: Fifty-five children and
      adolescents aged 6 to 18 years were evaluated with CBP (three visits), HBP (6
      days), and daytime ABP. Mean age was 12.3 +/- 2.9 (SD) years, 33 boys. According
      to the Task Force CBP criteria, 26 were hypertensives, 6 had high-normal BP
      (hypertensive group), and 23 were normotensives (normotensive group). RESULTS: In
      the hypertensive group, CBP was 130.8 +/- 7.6/72.5 +/- 8.1 mm Hg
      (systolic/diastolic), HBP 118.9 +/- 6.3/73.7 +/- 6.7, and ABP 130.8 +/- 8.1/75.5
      +/- 8.3. In the normotensive group, CBP was 112.8 +/- 8/63.1 +/- 6.3, HBP 106.7
      +/- 8.4/67.2 +/- 5.2, and ABP 123.9 +/- 7.2/72 +/- 4.3. Strong correlations (P <
      .001) were observed between CBP-HBP (r = 0.73/0.57, systolic/diastolic), CBP-ABP
      (r = 0.59/0.49), and HBP-ABP (r = 0.72/0.66). In normotensive subjects, ABP was
      higher than both CBP and HBP for systolic and diastolic BP (P < .001).
      Furthermore, systolic HBP was lower than CBP (P < .01), whereas the opposite was
      true for diastolic BP (P < .05). In hypertensive subjects systolic HBP was lower
      than both CBP and ABP (P < .001), whereas CBP did not differ from ABP. For
      diastolic BP no differences were found among measurement methods. CONCLUSIONS:
      These data suggest that, in contrast to adults in whom HBP is close to the levels
      of daytime ABP, in children and adolescents HBP appears to be significantly lower
      than daytime ABP. Until more data become available, caution is needed in the
      interpretation of HBP in children and adolescents.

PMID- 15485748
TI  - Cardiovascular and renal events in uncomplicated mild hypertensive patients with
      sustained and white coat hypertension.
AB  - BACKGROUND: The prognostic value of white coat hypertension (WCH) in
      uncomplicated patients with mild hypertension is not yet completely clear. We
      investigated cardiovascular outcomes in patients with mild hypertension and
      without left ventricular hypertrophy, diabetes mellitus, and associated
      cardiovascular and renal disease, with sustained hypertension (SH) and WCH.
      METHODS: The occurrence of fatal and nonfatal cardiovascular events was evaluated
      in 1038 patients with mild hypertension and 241 normotensive subjects. The
      presence of WCH was defined as clinic hypertension and daytime blood pressure
      <135/85 mm Hg. RESULTS: During follow-up (4.5 +/- 2.3 years, range 0.5 to 9.2
      years) the event rates per 100 patient-years in subjects with normotension, WCH,
      and SH were 0.27, 0.38, and 1.39, respectively. After adjustment for other
      covariates, Cox regression analysis showed that SH was an independent predictor
      of cardiovascular events (SH versus WCH, RR 5.17, 95% CI 2.04 to 13.1, P = 0
      .001), whereas there was no significant difference between normotension and WCH
      (normotension versus WCH, RR 0.93, 95% CI 0.22 to 3.98, P = .92). At the end of
      follow-up, drug therapy was less frequent and intensive in WCH than in SH.
      CONCLUSIONS: In this study of individuals with mild hypertension and without left
      ventricular hypertrophy, diabetes mellitus, and associated cardiovascular and
      renal disease, subjects with WCH, despite less frequent and intensive drug
      therapy, had a significantly better prognosis than those with sustained
      hypertension.

PMID- 15485749
TI  - Left ventricular hypertrophy and its regression in essential arterial
      hypertension. A tissue Doppler imaging study.
AB  - The mitral annulus velocities of Doppler transmitral flow and pulsed-wave tissue
      Doppler imaging (TDI) were sampled by echocardiography for the assessment of left
      ventricular (LV) diastolic function in 118 never-treated essential hypertensive
      patients with normal systolic function and compared with those of 59 normotensive
      healthy subjects matched for age and sex. A selected group (n = 26) of the
      hypertensive study population was observed after 1 year of pharmacologic
      antihypertensive treatment to determine the behavior of TDI parameters in
      relation to eventual regression of LV hypertrophy (LVH). We found that the TDI
      early myocardial diastolic wave (E(m)) was significantly lower both in concentric
      and eccentric LVH. In addition, TDI late myocardial diastolic wave (A(m)) was
      significantly higher in concentric remodeling and concentric and eccentric
      hypertrophy. The TDI E(m)/A(m) ratio was significantly lower in all geometric
      remodeling subgroups. The E/A ratio Doppler transmitral flow velocity measured
      showed that of the 118 patients, only 32 (25%) could really be discriminated from
      normal, whereas individual analysis for TDI E(m)/A(m) at the mitral annulus
      septal level showed that of 118 patients 108 (91%) could be discriminated from
      normal P < .001). The LV mass was significantly less after 1 year of treatment
      (LVH regression), and TDI parameters showed a trend toward normalization, in
      particular of TDI E(m)/A(m) at the annular septal level. Pulsed-wave TDI analysis
      could enable not only the early assessment of whether a patient is still in an
      adaptive or compensatory phase before transition to irreversible damage
      (pathologic phase) but also the detection of precocious LV global diastolic
      dysfunction. With regard to this, more extensive randomized studies are needed to
      evaluate the effect of different pharmacologic treatments (calcium antagonists,
      beta-blockers, angiotensin I and II inhibitors) on TDI parameters.

PMID- 15485750
TI  - Cross-sectional relations of urinary sodium excretion to cardiac structure and
      hypertrophy. The Framingham Heart Study.
AB  - BACKGROUND: Increased sodium intake has been positively associated with high
      blood pressure (BP) and hypertensive target organ damage, but associations with
      cardiac structure in nonhypertensive individuals have yielded inconsistent
      results. We tested the hypothesis that sodium intake is associated with left
      ventricular (LV) mass and left ventricular hypertrophy (LVH), independent of BP,
      in the community. METHODS: We analyzed the cross-sectional relationships between
      urinary sodium excretion and LV measurements in a community-based sample of 2660
      Framingham Offspring Study participants (mean age 58 years, 56% women and 44%
      men). Participants with known coronary artery disease, congestive heart failure,
      or renal failure as well as those using diuretics were excluded. Urinary sodium
      excretion was measured on a spot urine sample and was indexed to urinary
      creatinine. RESULTS: In sex-specific, multivariable linear regression models
      adjusting for covariates known to influence LV measurements, log urinary sodium
      was not associated with LV mass, wall thickness, end-diastolic dimensions, or
      left atrial size in either sex. Urinary sodium was not related to LVH defined as
      LV mass >/= sex-specific 80th percentile value. In analyses restricted to
      hypertensive individuals (n = 983, 470 women), urinary sodium was not associated
      with LV mass or LVH. CONCLUSIONS: In our large community-based sample, urinary
      sodium excretion was not related to LV mass, function, or hypertrophy.

PMID- 15485751
TI  - Concealment of electrocardiographically based diagnosis of left ventricular
      hypertrophy by anasarca.
AB  - BACKGROUND: Diagnosis of left ventricular hypertrophy (LVH) is primarily based on
      measurements of R- and S-waves from various electrocardiographic (ECG) leads.
      Recent information has shown that anasarca peripheral edema (AN) (defined as
      fluid accumulation diagnosed by weight gain, positive fluid intake/output
      records, and pitting edema in the lower extremities and rest of the body,
      particularly in the dorsal region) leads to attenuation in the amplitude of QRS
      complexes and consequently could interfere with the diagnosis of LVH. The
      objective of this study was to evaluate whether the diagnosis of LVH is concealed
      by AN. METHODS: Conventional ECG measurements and diagnostic binary
      characterization according to the Cornell, Sokolow-Lyon, and Romhilt-Estes
      systems were carried out in 14 patients with LVH (six patients with AN and eight
      patients admitted contemporaneously who did not gain weight during their
      hospitalization and who served as control subjects). The patients with AN were
      evaluated on admission (before the development of AN), and on the days of half of
      peak weight (HF-W) gain, peak weight (P-W) gain, and the lowest subsequent weight
      (L-W). The control subjects were evaluated on admission and at discharge.
      Analyses included the following: characterization by the three LVH diagnostic
      instruments mentioned previously; QRS amplitude measurements for the assessment
      of LVH before and after development of AN; and comparisons of the AN patients
      with the control subjects. RESULTS: Measurements and binary characterization was
      diagnostic of LVH on admission by design for all 14 patients. However, although
      such characterization remained unaltered for the control subjects, the patients
      with AN revealed statistically significant drops in all ECG measurements on the
      days of HF-W gain (P = .016 to .0005) and P-W gain (P = .02 to .0005), at which
      points the diagnosis of LVH could no longer anymore substantiated. CONCLUSIONS:
      The results of this study indicate that AN interferes with
      electrocardiographically based diagnosis of LVH. This has clinical implications
      because accurate characterization of the presence or absence of LVH is
      unattainable in patients with AN and should await abatement of the edematous
      state. The previously stated can be extrapolated to the patients with congestive
      heart failure who have gone on to develop right heart failure and AN, or to
      patients with end-stage renal failure who also reveal attenuation of the ECG QRS
      potentials at the stage of poor compensation of their edematous state.

PMID- 15485752
TI  - Hypertension in overweight and obese primary care patients is highly prevalent
      and poorly controlled.
AB  - BACKGROUND: Although the relationship between body weight and blood pressure (BP)
      is well established, there is a lack of data regarding the impact of obesity on
      the prevalence of hypertension in primary care practice. The objective of this
      study was to assess the prevalence of hypertension and the diagnosis, treatment
      status, and control rates of hypertension in obese patients as compared to
      patients with normal weight. METHODS: A cross-sectional point prevalence study of
      45,125 unselected consecutive primary care attendees was conducted in a
      representative nationwide sample of 1912 primary care physicians in Germany
      (HYDRA). RESULTS: Blood pressure levels were consistently higher in obese
      patients. Overall prevalence of hypertension (blood pressure >/=140/90 mm Hg or
      on antihypertensive medication) in normal weight patients was 34.3%, in
      overweight participants 60.6%, in grade 1 obesity 72.9%, in grade 2 obesity
      77.1%, and in grade 3 obesity 74.1%. The odds ratio (OR) for good BP control
      (<140/90 mm Hg) in diagnosed and treated patients was 0.8 (95% confidence
      interval [CI] 0.7-0.9) in overweight patients, 0.6 (95% CI 0.6-0.7) in grade 1,
      0.5 (95% CI 0.4-0.6) in grade 2, and 0.7 (95% CI 0.5-0.9) in grade 3 obese
      patients. CONCLUSIONS: The increasing prevalence of hypertension in obese
      patients and the low control rates in overweight and obese patients document the
      challenge that hypertension control in obese patients imposes on the primary care
      physician. These results highlight the need for specific evidence-based
      guidelines for the pharmacologic management of obesity-related hypertension in
      primary practice.

PMID- 15485753
TI  - Insulin receptor number is reduced in healthy offspring of patients with
      essential hypertension.
AB  - BACKGROUND: Epidemiologic studies have shown that healthy offspring of
      hypertensive patients exhibit many features of the metabolic syndrome, such as
      hyperinsulinemia, insulin resistance, and lipid disorders. Patients with
      essential hypertension have reduced numbers of insulin receptors. The aim of this
      study was to examine whether the number of insulin receptors is reduced in the
      erythrocytes of healthy offspring of hypertensive patients in comparison to the
      offspring of healthy normotensive subjects. METHODS: The study population
      consisted of 25 healthy offspring of patients with essential hypertension (group
      A) and 28 healthy offspring of healthy normotensive individuals (group B). The
      two groups were matched for sex, age, and body mass index. Systolic blood
      pressure (SBP) and diastolic blood pressure (DBP), resting heart rate (HR),
      plasma insulin levels, and human insulin receptor (hINR) number in erythrocytes
      were determined in each participant. RESULTS: Mean SBP, DBP, and resting HR were
      significantly higher in group A than in group B (121 +/- 13 v 110 +/- 10 mm Hg,
      78 +/- 6 v 73 +/- 8 mm Hg, and 76 +/- 4 v 72 +/- 6 beats/min; P < .01, P < .05,
      and P < .01, respectively). Plasma insulin levels were significantly higher,
      whereas hINR density was significantly lower, in group A than in group B (21 +/-
      7 v 15 +/- 6 pIU/mL, P < .01, and 5.6 +/- 1.4 v 6.8 +/- 1.3 receptors x 10(3)/red
      cell, P < .01, respectively). CONCLUSIONS: Our findings suggest that increased
      SBP, DBP, HR, plasma insulin levels, and decreased erythrocyte hINR density
      preexist in healthy offspring of patients with essential hypertension.

PMID- 15485754
TI  - Correlates of hypertension control in a primary care setting.
AB  - BACKGROUND: Numerous clinical trials have demonstrated reduction in
      cardiovascular events as a result of lowering blood pressure (BP). Despite these
      findings, BP control rates, especially in primary care settings, remain
      suboptimal. This study describes hypertension control and its predictors, using
      data from a sample of 631 adult patients drawn from an established primary care
      practice. METHODS: Data were obtained through chart review and patient survey
      during a 3-month period. The BP control was the outcome in a logistic regression
      model identifying demographic and clinical predictors of control. RESULTS:
      Compared to patients with low Framingham Risk Scores (FRS), individuals with
      moderate and high scores had reduced odds of achieving control (69% reduction,
      95% confidence interval [CI] 0.19-0.65; 82% reduction, 95% CI 0.10-0.36,
      respectively). Being female reduced the odds of control by 61% (95% CI 0.26
      0.66). Having diabetes mellitus (DM) (95% CI 0.21-0.79) or impaired fasting
      glucose (IFG; fasting glucose >109 but <126 mg/dL) (95% CI 0.10-0.40) reduced the
      odds of control by 64% and 82%, respectively. For each additional point on a
      physician-rated patient knowledge scale, the odds of having controlled BP
      increased 78% (95% CI 1.44-2.56). Each additional co-morbid condition positively
      associated with control (34% increase in odds, 95% CI 1.15-1.86). Age (95% CI
      0.98-1.02) and body mass index (BMI) (95% CI 0.97-1.04) had no effect.
      CONCLUSIONS: Higher FRS, female sex, DM, and IFG negatively correlated with
      control. Patient knowledge and number of co-morbid conditions correlated
      positively. Age and BMI did not correlate with control. The most disturbing
      finding in our study was that higher risk patients who stand to benefit most from
      BP control were least likely to be controlled, despite being on more
      antihypertensive medications. These findings may be helpful to primary care
      providers in reaching patient hypertension control goals.

PMID- 15485755
TI  - Nurse management for hypertension. A systems approach.
AB  - BACKGROUND: Standard office-based approaches to controlling hypertension show
      limited success. Such suboptimal hypertension control reflects in part the
      absence of both an infrastructure for patient education and frequent, regular
      blood pressure (BP) monitoring. We tested the efficacy of a physician-directed,
      nurse-managed, home-based system for hypertension management with standardized
      algorithms to modulate drug therapy, based on patients' reports of home BP.
      METHODS: We randomized outpatients requiring drug therapy for hypertension
      according to the Joint National Committee on Prevention, Detection, Evaluation,
      and Treatment of High Blood Pressure (JNC VI) criteria to receive usual medical
      care only (UC, n = 76) or usual care plus nurse care management intervention
      (INT, n = 74) over a 6-month period. RESULTS: Patients receiving INT achieved
      greater reductions in office BP values at 6 months than those receiving UC: 14.2
      +/- 18.1 versus 5.7 +/- 18.7 mm Hg systolic (P < .01) and 6.5 +/- 10.0 versus 3.4
      +/- 7.9 mm Hg diastolic, respectively (P < .05). At 6 months, we observed one or
      more changes in drug therapy in 97% of INT patients versus 43% of UC patients,
      and 70% of INT patients received two or more drugs versus 46% of UC. Average
      daily adherence to medication, measured by electronic drug event monitors, was
      superior among INT subjects (mean +/- SD, 80.5% +/- 23.0%) than among UC subjects
      (69.2 +/- 31.1%; t(113) = 2.199, P = .03). There were no significant adverse drug
      reactions in either group. CONCLUSIONS: Telephone-mediated nurse management can
      successfully address many of the systems-related and patient-related issues that
      limit pharmacotherapeutic effectiveness for hypertension.

PMID- 15485756
TI  - Antihypertensive and renoprotective efficacy and safety of losartan. A long-term
      study in children with renal disorders.
AB  - BACKGROUND: Hypertension is a major risk factor for progressive renal failure. We
      assessed the long term efficacy and safety of losartan in lowering blood pressure
      (BP) and in preserving renal function in hypertensive children with chronic renal
      disorders. METHODS: Losartan was used in 45 consecutive hypertensive children
      with chronic renal parenchymal disorders and mean glomerular filtration rate
      (GFR) 99.4 mL/min/1.73 m(2). Of the children, 21 had hypertension alone (H) and
      24 had both hypertension and proteinuria (H+P). Assessment was done at baseline
      and at preselected time points: visit I, <0.25 years; visit II, >/=0.25 and <0.5
      year;visit III, 0.5 to 1.0 year; and visit IV >1 year. Both BP control and GFR
      were the principal outcome measures, and proteinuria was a secondary outcome
      measure. RESULTS: The mean age was 12.85 years and follow-up was 2.42 years
      (visit IV). Compared with baseline the systolic, diastolic, and mean arterial BP
      (MABP) fell by 9 to 12 mm Hg (all P < .01) in visit I. Diastolic BP and MABP
      remained significantly lower in all visits (P < .05 to .001), whereas systolic BP
      was not statistically lower in visit II. In visit IV the proportion of
      normotensive children increased significantly compared with baseline (P < .03 for
      systolic BP, P < .0004 for diastolic BP). In the H+P subgroup, optimal reduction
      in proteinuria ranging from 66% to 71% occurred in visits II to IV (all P < .01).
      Mean GFR declined at a rate of 9.3 mL/min/1.73 m(2) /year before starting
      losartan, and 1.4 mL/min/1.73 m(2) /year subsequently (P = NS). On long term
      follow-up, GFR fell by 15.9 mL/min/1.73 m(2) in the H subgroup and by 5.5
      mL/min/1.73 m(2) in the H+P subgroup (P = NS). There was no correlation between
      BP measures and GFR or between the magnitude of BP lowering and proteinuria.
      Adverse effects (one serious) led to discontinuation of losartan in five children
      (11%). CONCLUSIONS: Losartan therapy was associated with prolonged and sustained
      antihypertensive and renoprotective benefits in children with a variety of
      chronic renal parenchymal disorders. Such benefit may be more pronounced in
      children with combined hypertension and proteinuria. The agent was well tolerated
      in the majority of the children.

PMID- 15485757
TI  - Families and the natural history of blood pressure. A 27-year follow-up study.
AB  - BACKGROUND: Previous studies on familial aggregation of blood pressure (BP) have
      reported data on family history of hypertension. Data on actual parental BP
      levels and the subsequent natural history of BP in their offspring are scarce.
      METHODS: In a population-based study with 596 children aged 5 to 19 years,
      cardiovascular risk factors were measured annually from 1975 through 2002.
      Parental data were obtained at baseline. Repeated BP measurements were studied as
      a function of tertiles of age-adjusted BP measured in their parents at baseline.
      RESULTS: Systolic BP during follow-up was higher in offspring whose parents were
      both in the highest tertile compared with children whose parents were not in the
      highest tertile (difference 2.7 mm Hg, 95% confidence interval 0.2 to 5.2).
      Having both parents in the highest tertile of diastolic BP resulted in a
      substantially higher diastolic BP ranging from 1.9 mm Hg at age 15 years to 8.5
      mm Hg at age 45 years. These differences were adjusted for age, sex, body mass
      index, total serum cholesterol, smoking habits, and alcohol consumption.
      CONCLUSIONS: The results of this study indicate that actual parental BP is an
      important predictor of BP development from childhood into young adulthood. This
      is important when constituting cardiovascular risk profiles for children and
      young adults.

PMID- 15485758
TI  - Central hemodynamics of hypertensive disorders in pregnancy.
AB  - BACKGROUND: Preeclampsia is characterized by an increase in peripheral
      vasoconstriction. Studies of central hemodynamics are limited. Noninvasive
      evaluation of aortic stiffness and pressure waveform is possible by applanation
      tonometry. We determined pulse wave velocity (PWV), augmentation index (AI),
      subendocardial viability ratio (SEVR), and the central to brachial pressure
      amplification in normotensive, hypertensive, and preeclamptic pregnancies.
      METHODS: In 51 normotensive, 38 hypertensive, and 33 preeclamptic pregnancies we
      measured carotid-femoral PWV. The AI, SEVR, and central pressures were determined
      by analysis of the aortic pressure waveform derived from the radial artery.
      Measurements were performed in lateral position after 10 min of rest. Linear
      regression models and ANOVA multiple comparisons were used for statistical
      analyses. RESULTS: There were no differences in age or other baseline
      characteristics. The mean PWV for the normotensive, hypertensive, and
      preeclamptic groups was 5.1 m/sec (SD 0.6), 6.2 m/sec (SD 1.0), and 7.0 m/sec (SD
      1.3), respectively. The AI was 6.7% (SD 14.0), 17.7% (SD 15.9), and 31.1% (SD
      12.4), respectively. The SEVR was 1.38 (SD 0.2), 1.50 (0.2), and 1.48 (0.3),
      respectively. Central to brachial pressure amplification was 1.6 (SD 0.2), 1.4
      (SD 0.2), and 1.3 (SD 0.2), respectively. After adjustment for blood pressure, no
      significant differences remained between the groups. CONCLUSIONS: In hypertensive
      and preeclamptic pregnancies, aortic stiffness and augmentation are significantly
      higher as compared to normotensive pregnancy. Amplification of central pulse
      pressure is significantly lower in hypertensive and preeclamptic pregnancies,
      resulting in relatively higher central pressure. Nevertheless, the supply and
      demand ratio of the heart is not impaired in hypertensive and preeclamptic
      pregnancies.

PMID- 15485759
TI  - Treatment by n-acetylcysteine and melatonin increases cardiac baroreflex and
      improves antioxidant reserve.
AB  - BACKGROUND: The aims of this study were to investigate the effects of melatonin
      and n-acetylcysteine on the baroreflex sensitivity and to verify whether those
      effects were correlated with their antioxidant capacity in Wistar-Kyoto and
      spontaneously hypertensive rats (SHR). METHODS: Rats were treated with 30
      mg/kg/day of melatonin or 4 g/kg/day of n-acetylcysteine for 4 weeks. Changes in
      mean arterial pressure, heart rate, plasma norepinephrine, and epinephrine were
      measured in conscious rats after an intravenous injection of phenylephrine or
      sodium nitroprusside. RESULTS: The SHR were characterized by decreased reflex
      chronotropic responses to phenylephrine and sodium nitroprusside (P < .001 and P
      < .001), as well as by an enhanced increase in plasma catecholamine
      concentrations in response to sodium nitroprusside (P < .001). Melatonin and n
      acetylcysteine produced a significant reduction in mean arterial pressure and
      heart rate in SHR (P < .001). Melatonin and n-acetylcysteine improved bradycardic
      (P < .001) and tachycardic (P < .001) baroreflex responses in SHR without
      modifying catecholamine responses. The antioxidant reserve, which was reduced in
      SHR as reflected by the lower glutathione peroxidase activity in plasma (P <
      .05), was normalized by n-acetylcysteine and melatonin (P < .05). n
      acetylcysteine (P < .001) and melatonin (P < .05) increased glutathione
      peroxidase activity in erythrocytes from SHR. CONCLUSIONS: The results of the
      present study suggest that melatonin and n-acetylcysteine improve the baroreflex
      response in SHR in correlation with the antioxidant effects of these substances.

PMID- 15485760
TI  - Prevalence of isolated systolic and isolated diastolic hypertension subtypes in
      China.
AB  - BACKGROUND: Isolated systolic hypertension (ISH), more so than any other
      hypertension subtype, increases the risk for stroke and coronary heart disease.
      The prevalence of ISH versus other hypertension subtypes in the general Chinese
      adult population is not known. METHODS: The prevalence of isolated systolic and
      isolated diastolic hypertension (IDH) was examined in a representative national
      sample of 15,540 Chinese adults aged 35 to 74 years. Three seated blood pressure
      (BP) measurements taken after 5 min of rest were averaged and hypertension
      subtypes were defined among individuals not receiving antihypertensive therapy as
      follows: ISH as systolic BP >/=140 mm Hg and diastolic BP <90 mm Hg; IDH as
      systolic BP <140 mm Hg and diastolic BP >/=90 mm Hg; and combined
      systolic/diastolic hypertension (SDH) as a systolic BP >/=140 mm Hg and diastolic
      BP >/=90 mm Hg. RESULTS: Overall, 7.6% of the Chinese adult population had ISH,
      7.4% had SDH, and 4.4% had IDH. The prevalence of ISH increased with age and was
      more common in older women than in older men. Stage 1 hypertension was much more
      prevalent than stage 2 hypertension among all hypertension subtypes. The
      prevalence of SDH, IDH, and ISH (women, only) were higher in northern China than
      southern. The prevalence of ISH and SDH (women, only) were higher among rural
      residents versus urban residents. CONCLUSIONS: These data document high rates of
      ISH in China. Given the risk of cardiovascular disease associated with ISH, our
      findings underscore the critical need for enhanced hypertension screening and
      treatment programs in China.

PMID- 15485761
TI  - Racial/ethnic differences in hypertension and hypertension treatment and control
      in the multi-ethnic study of atherosclerosis (MESA).
AB  - BACKGROUND: Most previous studies investigating the association between ethnicity
      and hypertension focused on differences between African Americans and whites and
      did not include other racial/ethnic groups such as Chinese or Hispanics. METHODS:
      We used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population
      based study of 6814 adults without clinical cardiovascular disease, to examine
      the association between ethnicity and hypertension and hypertension treatment
      among white, African American, Chinese, and Hispanic ethnic groups. RESULTS: The
      prevalence of hypertension, defined as systolic blood pressure (BP) <140 mm Hg
      and diastolic BP <90 mm Hg or self-reported treatment for hypertension, was
      significantly higher in African Americans compared to whites (60% v 38%; P <
      .0001), whereas prevalence in Hispanic (42%) and Chinese participants (39%) did
      not differ significantly from that in whites. After adjustment for age, body mass
      index, prevalence of diabetes mellitus, and smoking, African American (odds ratio
      [OR] 2.21; 95% confidence interval [95% CI] 1.91-2.56) and Chinese (OR 1.30; 95%
      CI 1.07-1.56) ethnicity were significantly associated with hypertension compared
      to whites. Among hypertensive MESA participants, the percentage of treated but
      uncontrolled hypertension in whites (24%) was significantly lower than in African
      Americans (35%, P < .0001), Chinese (33%, P = .003), and Hispanics (32%, P =
      .0005), but only African-American race/ethnicity remained significantly
      associated with treated but uncontrolled hypertension after controlling for
      socioeconomic factors (OR 1.35; 95% CI 1.07-1.71). Diuretic use was lowest in the
      Chinese (22%) and Hispanic participants (32%) and was significantly lower in
      these groups compared with white participants (47%; P < .0001 for both
      comparisons). CONCLUSIONS: Programs to improve hypertension treatment and control
      should focus on a better understanding of differences in the prevalence of
      hypertension and hypertension control among minority groups in the United States,
      especially African Americans, compared with whites, and on techniques to prevent
      hypertension and improve control in high-risk groups.

PMID- 15485762
TI  - The association of regional fat depots with hypertension in older persons of
      white and African American ethnicity.
AB  - BACKGROUND: Fat distribution has been shown to be a strong correlate of
      hypertension, independent of general obesity. However, population-based studies
      are lacking on the association of regional fat depots with hypertension. METHODS:
      The present study is a cross-sectional analysis of 2969 individuals in the
      Health, Aging and Body Composition Study (915 men of white ethnicity and 535 of
      African American; and 833 women of white ethnicity and 686 of African American)
      who were 70 to 79 years of age. Fat depots were measured by computed tomography.
      RESULTS: The prevalence of hypertension was 57%. Among those with hypertension,
      70% reported antihypertensive treatment. In logistic regression analyses,
      visceral fat was strongly associated with hypertension (odds ratios for each
      standard deviation increase in the area of visceral fat: 1.28, P < .0001) after
      adjustment for age, sex, ethnicity, site, height, smoking status, pack-years of
      smoking, alcohol consumption status, amount of alcohol consumption, and physical
      activity. Moreover, the association was the strongest in individuals with the
      least amount of total body fat. Besides visceral fat, subcutaneous fat and thigh
      intermuscular fat were also associated with hypertension in African Americans.
      CONCLUSIONS: Larger amounts of visceral fat may indicate a high risk of
      hypertension in older adults, especially in lean individuals.

PMID- 15485763
TI  - Association of blunted nighttime blood pressure dipping with coronary artery
      stenosis in men.
AB  - BACKGROUND: The aim of this work was to study the association between blunted
      nighttime dipping of blood pressure (BP) and coronary artery stenosis in men.
      METHODS: Sixty-eight men (aged 52 +/- 11 years) with coronary artery disease
      (CAD) defined as >/=70% diameter stenosis, and a control group of 68 men, matched
      for age and risk factors without angiographic CAD were studied by ambulatory
      blood pressure monitoring. Patients were defined as nondippers when the nighttime
      systolic and diastolic BP decrease was <10%. Medications included beta-blockers
      in 20 (15%), calcium antagonists in 39 (29%), angiotensin-converting enzyme
      inhibitors in 44 (32%), angiotensin receptor blockers in 21 (15%), and diuretics
      in 37 (27%) patients. A logistic regression model was used to define independent
      predictors of angiographic CAD. Covariates were symptoms, total cholesterol,
      daytime BP, and nondipping. RESULTS: A larger proportion of patients with CAD
      were nondippers as compared to control subjects (49 [72%] v 31 [46%], P < .005).
      In a logistic regression model, nondipping was associated with coronary artery
      stenosis independent of other clinical parameters (odds ratio 3.6, 95% confidence
      interval 1.6-8.8). CONCLUSIONS: Blunted nighttime dipping of BP is independently
      associated with angiographic coronary artery stenosis in men.

PMID- 15485764
TI  - Increaseed expression of mRNA for regulator of G protein signaling domain
      containing Rho guanine nucleotide exchange factors in aorta from stroke-prone
      spontaneously hypertensive rats.
AB  - BACKGROUND: Rho guanine nucleotide exchange factors (RhoGEF) link activation of G
      protein-coupled receptors (GPCR) to RhoA/Rho-kinase signaling. This cellular
      signaling pathway regulates vascular tone and is implicated in hypertension. The
      RhoGEF, providing this coupling, contain the regulator of G protein signaling
      (RGS) domain. We hypothesized higher mRNA expression levels for these RhoGEF in
      aorta from stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: We
      measured mRNA expression by semiquantitative reverse transcriptase-polymerase
      chain reaction in the aorta of Wistar-Kyoto rats (WKY) and SHRSP. The protein
      expression level of p115RhoGEF was examined by Western Blot, too. RESULTS: Our
      results showed that mRNA for RGS domain containing RhoGEF is higher in SHRSP.
      CONCLUSION: The results of this study indicate that RhoGEF may contribute to
      increased activation of RhoA/Rho-kinase pathway in hypertension.

PMID- 15485765
TI  - Microalbuminuria and cardiovascular risk.
AB  - Microalbuminuria is a marker for generalized vascular dysfunction. Its prevalence
      in United States and European general population surveys ranges from 6% to 10%.
      Increased risk for cardiovascular morbidity and mortality begins with albumin
      excretion rates that are well within normal limits. Although microalbuminuria
      interacts with the traditional cardiovascular risk factors, it has an independent
      relationship to renal and cardiovascular outcomes. For example, microalbuminuria
      doubles the risk for a cardiovascular event in patients with type 2 diabetes
      mellitus even after adjusting for the usual risk factors. Elevated rates of
      urinary albumin excretion predict target organ damage, notably renal disease, but
      are also related to left ventricular dysfunction, stroke, and myocardial
      infarction. Screening for microalbuminuria, which is recommended by several
      expert committees and associations, has become a readily accessible procedure.
      Screening can give clinicians prognostic information concerning cardiovascular
      risk and assist in guiding therapy. The goal of treatment is to prevent
      progression of, and even to reverse, microalbuminuria. Abundant evidence
      demonstrates that antihypertensive therapy is an important key to the control of
      urinary albumin excretion, and blockade of the renin-angiotensin system (with
      angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers) is
      the treatment of choice. These drugs have successfully halted or delayed the
      progression to nephropathy and have reversed elevated rates of albumin excretion
      to normal values, even when blood pressure reduction has been minimal.

PMID- 15485766
TI  - Female sex hormones, salt, and blood pressure regulation.
AB  - There are gender-associated differences in blood pressure (BP) in humans, with
      men having higher BP than age-matched pre-menopausal women and being at greater
      risk for cardiovascular and renal diseases. The mechanisms responsible for the
      gender differences in BP control and regulation are not clear, although there is
      some evidence that interactions between sex hormones and the kidneys could play a
      role. However, the response to salt in pre- and post-menopausal women, and in
      particular the influence of exogenous and endogenous female sex hormones on renal
      hemodynamics and tubular segmental sodium handling, have been poorly
      investigated. Recently we have shown that both endogenous and exogenous female
      sex hormones markedly influence the systemic and renal hemodynamic response to
      salt. We have found that BP in young normotensive women, regardless of oral
      contraceptive use, is rather insensitive to salt. However, the renal hemodynamic
      and the tubular responses to salt vary significantly during the normal menstrual
      cycle and with the administration of oral contraceptives. Furthermore, after the
      menopause, BP tends to become salt sensitive, a pattern that could be due to
      aging as well as to the modification of the sex hormone profile. These
      observations provide new insights pertaining to potential mechanisms explaining
      the lower incidence of cardiovascular disease and progression of renal disease in
      pre-menopausal women (which tend to disappear with the menopause); these
      observations also emphasize the importance of considering more carefully the
      phase of the menstrual cycle whenever conducting physiologic studies in women and
      enrolling women in clinical studies. Finally, increased salt sensitivity in
      menopausal women strongly encourages the use of diuretics.

PMID- 15485767
TI  - JNC-7 versus renin-based strategies for optimal antihypertensive drug treatment.
      Another look at the evidence.

PMID- 15485768
TI  - Delivery of bioactive molecules into the cell: the Trojan horse approach.
AB  - In recent years, vast amounts of data on the mechanisms of neural de- and
      regeneration have accumulated. However, only in disproportionally few cases has
      this led to efficient therapies for human patients. Part of the problem is to
      deliver cell death-averting genes or gene products across the blood-brain barrier
      (BBB) and cellular membranes. The discovery of Antennapedia (Antp)-mediated
      transduction of heterologous proteins into cells in 1992 and other "Trojan horse
      peptides" raised hopes that often-frustrating attempts to deliver proteins would
      now be history. The demonstration that proteins fused to the Tat protein
      transduction domain (PTD) are capable of crossing the BBB may revolutionize
      molecular research and neurobiological therapy. However, it was only recently
      that PTD-mediated delivery of proteins with therapeutic potential has been
      achieved in models of neural degeneration in nerve trauma and ischemia. Several
      groups have published the first positive results using protein transduction
      domains for the delivery of therapeutic proteins in relevant animal models of
      human neurological disorders. Here, we give an extensive review of peptide
      mediated protein transduction from its early beginnings to new advances, discuss
      their application, with particular focus on a critical evaluation of the
      limitations of the method, as well as alternative approaches. Besides
      applications in neurobiology, a large number of reports using PTD in other
      systems are included as well. Because each protein requires an individual
      purification scheme that yields sufficient quantities of soluble, transducible
      material, the neurobiologist will benefit from the experiences of other
      researchers in the growing field of protein transduction.

PMID- 15485769
TI  - Retrograde propagation of GDNF-mediated signals in sympathetic neurons.
AB  - Glial cell line-derived neurotrophic factor (GDNF) family ligands are target
      derived trophic factors for several neuronal subpopulations. They promote
      survival and neurite outgrowth through binding to specific members of the GDNF
      family receptor alpha (GFR alpha) and subsequent activation of the RET tyrosine
      kinase receptor. Using compartmentalized cultures of sympathetic neurons, we have
      studied the mechanism of GDNF retrograde signaling. Our results demonstrate the
      presence of GDNF receptors RET and GFR alpha 1 in the two cellular compartments,
      cell bodies and distal axons. Addition of GDNF to either compartment initiated
      local signaling, including activation of RET and its downstream effectors AKT and
      ERK1/2. Addition of GDNF to distal axons induced a retrograde signal leading to
      neuronal survival and neurite outgrowth. Retrograde signaling was associated with
      retrograde transport of radiolabeled GDNF and GFR alpha 1, as well as activation
      of RET and AKT, but not of ERK1/2, in cell bodies. No anterograde signal
      propagation or transport was observed. Our results suggest a general mechanism
      for retrograde signaling initiated at distal axons through tyrosine kinase
      receptors.

PMID- 15485770
TI  - Phosphodiesterase-I alpha/autotaxin controls cytoskeletal organization and FAK
      phosphorylation during myelination.
AB  - Myelination within the central nervous system (CNS) involves substantial
      morphogenesis of oligodendrocytes requiring plastic changes in oligodendrocyte
      extracellular matrix (ECM) interactions, that is, adhesion. Our previous studies
      indicated that a regulator of such adhesive plasticity is oligodendrocyte
      released phosphodiesterase-I alpha/autotaxin (PD-I alpha/ATX). We report here,
      that PD-I alpha/ATX's adhesion antagonism is mediated by a protein fragment
      different from the one that stimulates tumor cell motility. Furthermore, PD-I
      alpha/ATX's adhesion-antagonizing fragment causes a reorganized distribution of
      the focal adhesion components vinculin and paxillin and an integrin-dependent
      reduction in focal adhesion kinase (FAK) phosphorylation at tyrosine residue 925
      (pFAK-925). In vivo, a similar reduction in pFAK-925 occurs at the onset of
      myelination when PD-I alpha/ATX expression is significantly upregulated. Most
      importantly, it can also be induced by the application of exogenous PD-I
      alpha/ATX. Our data, therefore, suggest that PD-I alpha/ATX participates in the
      regulation of myelination via a novel signaling pathway leading to changes in
      integrin-dependent focal adhesion assembly and consequently oligodendrocyte-ECM
      interactions.

PMID- 15485771
TI  - Migrating and myelinating potential of neural precursors engineered to
      overexpress PSA-NCAM.
AB  - Polysialic acid (PSA) on NCAM is an important modulator of cell-cell interactions
      during development and regeneration. Here we investigated whether PSA
      overexpression influences neural cell migration and myelination. We stably
      expressed a GFP-tagged polysialytransferase, PSTGFP, in mouse neurospheres and
      induced prolonged PSA synthesis. Using a chick xenograft assay for migration, we
      show that PSA can instruct precursor migration along the ventral pathway. PSA
      persistence did not change neural precursor multipotentiality in vitro but
      induced a delay in oligodendrocyte differentiation. PSTGFP+ precursors showed
      widespread engraftment in shiverer brain, closely similar to that observed with
      control precursors expressing a fluorescent protein. Initially, myelination by
      oligodendrocytes was delayed but, eventually, down-regulation of PSTGFP occurred,
      allowing myelination to proceed. Thus down-regulation of polysialyltransferases
      takes place even in cells where its RNA is under the control of a heterologous
      promoter and engineering PSA overexpression in neural precursors does not cause
      irreversible unphysiological effects.

PMID- 15485773
TI  - Comparison of myelin, axon, lipid, and immunopathology in the central nervous
      system of differentially myelin-compromised mutant mice: a morphological and
      biochemical study.
AB  - The present study was carried out to compare different myelin-compromised mouse
      mutants with regard to myelin morphology in relation to axon-, lipid-, and
      immunopathology as a function of age. Mouse mutants deficient in the myelin
      associated glycoprotein (MAG) and myelin basic protein (MBP) display subtle and
      severe myelin pathologies in the central nervous system (CNS), respectively.
      Animals doubly deficient in MAG and the neural cell adhesion molecule (NCAM) show
      defects similar to those present in MAG single mutants while mice deficient in
      MAG and the nonreceptor type tyrosine kinase Fyn are severely hypomyelinated, in
      addition to the MAG-specific myelin abnormalities. These mutant mice showed
      distinct myelin pathologies in different regions of the central nervous system
      and generally displayed a decrease in axonal integrity with age. Myelin pathology
      did not correlate locally with axon transection and with an involvement of the
      immune system as seen by numbers of CD3-positive lymphocytes and MAC-3-positive
      macrophages. Interestingly, the degree of these cellular abnormalities also did
      not correlate with abnormalities in levels of phospholipids, arachidonic acid,
      cholesterol, and apolipoprotein E (apoE). Moreover, these changes in lipid
      metabolism, including immune system-related arachidonic acid, preceded cellular
      pathology. The combined observations point to differences, but also similarities
      in the relation of myelin, axon, and immunopathology with genotype, and to a
      common aggravation of the phenotype with age.

PMID- 15485772
TI  - Versican V2 and the central inhibitory domain of Nogo-A inhibit neurite growth
      via p75NTR/NgR-independent pathways that converge at RhoA.
AB  - Myelin is a major obstacle for regenerating nerve fibers of the adult mammalian
      central nervous system (CNS). Several proteins including Nogo-A, myelin
      associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp) and the
      chondroitin-sulfate proteoglycan (CSPG) Versican V2 have been identified as
      inhibitory components present in CNS myelin. MAG, OMgp as well as the Nogo
      specific domain Nogo-66 exert their inhibitory activity by binding to a neuronal
      receptor complex containing the Nogo-66 receptor NgR and the neurotrophin
      receptor p75(NTR). While this suggests a converging role of the p75(NTR)/NgR
      receptor complex for myelin-derived neurite growth inhibitors, we show here that
      NgR/p75(NTR) is not required for mediating the inhibitory activity of the two
      myelin components NiG, unlike Nogo-66 a distinct domain of Nogo-A, and Versican
      V2. Primary neurons derived from a complete null mutant of p75(NTR) are still
      sensitive to NiG and Versican V2. In line with this result, neurite growth of
      p75(NTR) deficient neurons is still significantly blocked on total bovine CNS
      myelin. Furthermore, modulation of RhoA and Rac1 in p75(NTR)-/- neurons persists
      with NiG and Versican V2. Finally, we demonstrate that neither NiG nor Versican
      V2 interact with the p75(NTR)/NgR receptor complex and provide evidence that the
      binding sites of NiG and Nogo-66 are physically distinct from each other on
      neural tissue. These results indicate not only the existence of neuronal
      receptors for myelin inhibitors independent from the p75(NTR)/NgR receptor
      complex but also establish Rho GTPases as a common point of signal convergence of
      diverse myelin-induced regeneration inhibitory pathways.

PMID- 15485774
TI  - Axonal responses to cellularly delivered NT-4/5 after spinal cord injury.
AB  - Neurotrophic factors delivered to the injured spinal cord have been shown to
      enhance axonal growth, prevent neuronal degeneration and partially improve
      sensorimotor function. The present study examined the effects of NT-4/5 on growth
      of spinal and supraspinal axons, glia, and functional outcome after spinal cord
      injury. Adult Fischer 344 rats received spinal cord dorsal hemisections or
      complete transections at the midthoracic level. Fibroblasts modified to secrete
      NT-4/5 or green fluorescent protein as controls were immediately grafted to the
      lesion site. Axonal growth responses were determined between 3 and 6 months
      postinjury by retrograde and anterograde tracing and immunohistochemistry. Motor
      axons, coerulospinal, reticulospinal, and propriospinal axons responded to NT-4/5
      delivery after thoracic spinal cord injury with significantly increased axonal
      penetration into NT-4/5 secreting grafts compared to GFP-expressing control
      grafts. Axonal growth beyond NT-4/5-producing grafts and functional recovery were
      not observed. Numerous Schwann cells, but not oligodendrocytes, were present
      within NT-4/5-secreting grafts and remyelinated axons inside the graft. Thus, NT
      4/5 and BDNF appear to be interchangeable to elicit substantial axonal growth in
      the injured spinal cord.

PMID- 15485775
TI  - FLRT3 is expressed in sensory neurons after peripheral nerve injury and regulates
      neurite outgrowth.
AB  - We used a molecular screen to identify genes upregulated in regenerating adult
      rat dorsal root ganglion cells. FLRT3 mRNA and protein characterized by a
      fibronectin type III domain and a leucine-rich repeat motif was upregulated in
      damaged sensory neurons. The protein was then transported into their peripheral
      and central processes where the FLRT3 protein was localized to presynaptic axon
      terminals. In vitro, the FLRT3 protein was expressed at the cell surface,
      regulated neurite outgrowth in sensory neurons, but did not exhibit homophilic
      binding. FLRT3 was widely expressed in the developing embryo, particularly in the
      central nervous system and somites. However, in the adult, we found no evidence
      for accumulation or reexpression of the FLRT3 protein in damaged axons of the
      central nervous system. We conclude that FLRT3 codes for a putative cell surface
      receptor implicated in both the development of the nervous system and in the
      regeneration of the peripheral nervous system (PNS).

PMID- 15485776
TI  - [Differentiation of bone marrow-derived stem cells in injured rat brain tissue].
AB  - OBJECTIVE: To investigate the differentiation of bone marrow-derived stem cells
      (BMDSCs) migrated from blood circulation and resided in the injured brain tissue.
      METHODS: Brain injury model was established by iridectomy in the right cerebral
      cortex of female SD rats. Twenty-four hours after brain injury, the female rats
      received the implantation of green fluorescence protein (GFP)-labeled BMDSCs from
      male SD rats and were sacrificed at 2, 4 and 8 weeks after the implantation.
      Fluorescent immunohistochemistry for CD11b and glial fibrillary acidic protein
      (GFAP) on the brain sections was used to detect the GFP-positive cells. RESULTS:
      One week after the transplantation of the GFP-labeled BMDSCs, 3.53% of the
      peripheral blood white cells were GFP-positive; at 4 weeks and 8 weeks, a
      significant number of GFP-positive cells were found at the injury sites, some of
      which expressed CD11b and others expressed GFAP. CONCLUSION: GFP-labeled BMDSCs
      can migrate to the injured brain tissue and differentiate into cells that express
      microglia- and astrocytes-specific antigens.

PMID- 15485777
TI  - [Association of CTLA-4 promoter -1722 polymorphism with systemic lupus
      erythematosus in Chinese].
AB  - OBJECTIVE: To investigate the possible association of cytotoxic T lymphocyte
      associated antigen 4 (CTLA-4) promoter -1722 polymorphism with systemic lupus
      erythematosus (SLE) in the population in southern China. METHODS: A total of 103
      SLE patients (13 males and 90 females with an average age of 33.63+/-12.58 years)
      diagnosed according to the SLE diagnostic criteria of the American College of
      Rheumatology revised in 1982 and 110 healthy ethnically matched controls (21
      males and 89 females with an average age of 27.49+/-8.60 years), all from
      southern China, were enrolled in the study. DNA was extracted from EDTA-treated
      blood samples according to the standard isolation procedure. The restriction
      fragment length polymorphism-polymerase chain reaction was used to analyze CTLA-4
      promoter-1722 polymorphism in SLE patients and healthy controls. RESULTS:
      Compared with the controls, the SLE patients had higher frequencies of TC
      genotype (42% vs 58%, P<0.05) and lower frequency of CC genotype (25% vs 15%,
      P<0.05). There were no significant differences in the frequencies of TT genotype,
      alleles and phenotypes between SLE patients and controls; however, significant
      differences in the frequencies of TT genotype and alleles of CTLA-4 promoter 
      1722 were found among different races (P<0.05). CONCLUSION: CTLA-4 promoter -1722
      polymorphism appears to be associated with SLE susceptibility in southern Chinese
      population.

PMID- 15485778
TI  - [Effect of total Panax notoginseng saponins on the activity of human endothelial
      nitric oxide synthase gene promoter].
AB  - OBJECTIVE: To study the mechanism of total Panax notoginseng saponin (tPNS) in
      regulating the transcription activity of human endothelial nitric oxide synthase
      (heNOS) gene promoter. METHODS: With gene recombination technique, we subcloned
      the heNOS gene promoter sequence (from -1 to -1 600 bp) into the BglII/HindIII
      sites of the firefly luciferase reporter gene vector, pGL2-Basic (Promega), to
      yield the recombinant plasmid designated as peNOS-Luc. With lipofectamine-
      mediated co-transfection technique, peNOS-Luc, pGL2-Basic and pCMV-beta were
      cotransfected into NIH3T3 cells, which were treated with lipopolysaccharide
      (LPS), tPNS and transforming growth factor beta1 (TGFbeta1) respectively. The
      relative activities (Luc/beta-gal) were subsequently determined in the cell
      lysates to evaluate the effects of these 3 factors on the activity of heNOS gene
      promoter. RESULTS: Double restriction enzyme digestion and sequencing both
      confirmed that the recombinant plasmid, peNOS-Luc, was constructed correctly,
      which could be effectively expressed in NIH3T3 cells. Upon LPS stimulation, the
      luciferase activity was obviously decreased, contrary to the results of tPNS and
      TGFbeta1 treatment, and between the latter two agents, TGFbeta1 produced higher
      transcription activity. CONCLUSIONS: A firefly luciferase reporter gene vector
      containing heNOS gene promoter sequence has been constructed correctly. tPNS can
      up-regulate the activity of heNOS gene promoter in NIH3T3 cells.

PMID- 15485779
TI  - [Effects of allogeneic hematopoietic stem cell transplantation with very-high
      dose conditioning regimen for refractory leukemia].
AB  - OBJECTIVE: To explore the regimen-related toxicity (RRT) and therapeutic effects
      of very-high-dose conditioning regimen combined with induction of graft-versus
      leukemia (GVL) effects in allogeneic hematopoietic stem cell transplantation
      (allo-HSCT) for refractory leukemia with unattainable complete remission (CR)
      before transplantation. METHODS: Eighteen patients who failed to obtain CR before
      transplantation received very-high-dose conditioning regimen protocol
      (experimental group), and 62 patients with acute leukemia with CR or with chronic
      myeloid leukemia in the chronic phase before transplantation received total body
      irradiation plus cyclophosphamide (CTX) or modified BuCY (hydroxyurea, busulfan,
      Ara-C, CTX) protocol (control group). In patients with refractory leukemia who
      did not develop graft-versus-host disease (GVHD) 30 d after the transplantation,
      GVL was induced by rapid reduction of the dosage of cyclosporin A or by donor
      lymphocytic infusion. The incidence and mortality of RRT and the rates of CR,
      GVHD and leukemia relapse after transplantation were investigated. Kaplan-Meier
      survival analysis model was used to estimate the disease-free survival (DFS) rate
      at 3 years post-transplantation. RESULTS: Except for one patient in the
      experimental group and two in the control group who died of transplantation-
      related complications, all the other patients obtained hematopoietic
      reconstitution. The total incidence of RRT was 100% in both groups, involving
      most frequently the stomach and intestines at the rate as high as 83.3% in the
      experimental group and 85.5% in the control group. RRT involving the oral cavity
      occurred in 44.4% and 62.9%, and that involving the bladder in 16.7% and 33.9% of
      the cases in the experimental group and control group, respectively, all similar
      between the groups (P=0.823, 0.172 and 0.244, respectively). The RRT mortality
      was 0 and 5% in the experimental and control groups, respectively (P=0.341). With
      the exception of one patient who died of infection, all the other patients
      treated with very-high-dose conditioning regimen obtained CR. The incidences of
      acute/chronic GVHD were 58.8%/92.6% and 40.0%/55.8%, respectively, in the
      experimental and control groups. The incidence of leukemia relapse was 11.8% and
      18.3%, and DFS at 3 years after transplantation was (61.2+/-12.3)% and (65.0+/
      7.4)% (P=0.6311) in the two groups, respectively. CONCLUSION: Consecutive very
      high-dose conditioning regimen combined with GVL induction after transplantation
      can increase the rate of CR and DFS, without increasing RRT incidence and
      mortality in allo-HSCT for the refractory leukemia with unattainable CR pre
      transplantation.

PMID- 15485780
TI  - [Skin temperature changes in Wistar rats with second-degree scald injury in hot
      and humid environment after cooling therapy].
AB  - OBJECTIVE: To observe the changes in skin temperature after cooling therapy
      immediate following superficial second-degree scald injury in Wistar rats in a
      hot and humid environment, and evaluate the effect of the dressing materials for
      the cooling therapy. METHODS: Twenty-four Wistar rats were randomly divided into
      normal temperature control (NTC), normal temperature cooling therapy (NCT), hot
      and humid control (HHC), and hot and humid cooling therapy (HCT) groups (n=6).
      Different interventions were applied to the scalded rats: dry bulb temperature
      (Tdb) of 26.33+/-1.29 degree with a relative humidity (rh) of 71.05%+/-4.57% for
      the two normal temperature groups, and Tdb 35.33+/-0.35 degree with rh of
      70.81%+/-1.38% for the two hot and humid environment groups. The dressing
      materials for the cooling therapy were applied to the two cooling therapy groups
      but not for the two control groups. The exposure time for the therapy was 125
      min, and the skin temperature was measured every 20 min, starting from 5 min
      after the scald. RESULTS: The skin temperature rose in hot and humid environment
      and decreased when cold therapy was applied (P<0.001). Interactions were found
      between the exposure time and environmental temperature (P<0.002), between the
      exposure time and cooling therapy (P<0.05), and between these 3 factors (P<0.05)
      to influence the skin temperature, which was 1.92+/-2.13 degrees Celsius lower in
      NCT group than in NTC group, and 2.36+/-1.03 degrees Celsius lower in HCT group
      than in HHC group. CONCLUSION: The dressing materials for cooling therapy
      effectively reduce the skin temperature at the site of the scald injury to
      prevent the progression of heat-induced injury and the unfavorable effects of the
      heat remaining on the scalded skin.

PMID- 15485781
TI  - [Neuroprotective effects of Naoxintong against neuronal injury in hippocampal CA1
      region following transient forebrain ischemia in rats].
AB  - OBJECTIVE: To examine the neuroprotective effects of Naoxintong and
      Zhongfenghuichunwan on neuronal injury in CA1 region of rat hippocampus following
      transient forebrain ischemia. METHODS: Transient rat forebrain ischemia for 15
      min was induced by modified four-vessel occlusion method. The density of survived
      pyramidal cells (neurons per 1 mm linear length) in CA1 region of the hippocampus
      was measured under light microscope. RESULTS: In Naoxintong or nimodipine-treated
      rats, the density of survived pyramidal cells in CA1 region was significantly
      greater than that of saline group (P<0.05, P<0.001, respectively), but oral
      administration of Zhongfenghuichunwan had no obvious effect on ischemia-induced
      neuronal damage in CA1 region. CONCLUSION: Naoxintong can protect CA1 neurons
      against ischemic insult in rats.

PMID- 15485782
TI  - [Gene expression profiles in different tissues of human nasopharyngeal
      carcinoma].
AB  - OBJECTIVE: To screen the genes that may play an important role in the
      carcinogenesis of nasopharyngeal carcinoma (NPC). METHODS: Microdissection and
      cDNA genechip hybridization techniques were used to examine the differentially
      expressed genes in NPC tissue, the surrounding and adjacent tissues of NPC, and
      the nasopharyngeal inflammation tissue. The fluorescent signals on cDNA chip were
      scanned and the results of hybridization analyzed by image processing software.
      RESULTS: Many differentially expressed genes were identified between the three
      samples, including many different types of genes, such as those responsible for
      signal and protein transmission, oncogene and tumor suppression genes, immune
      associated genes, apoptosis genes and DNA binding and transcription factor genes.
      CONCLUSION: The carcinogenesis of NPC involves many genes of a variety of types,
      suggesting its complex process.

PMID- 15485783
TI  - [Application of biotin-avidin system in targeted magnetic resonance imaging].
AB  - OBJECTIVE: To improve the sensitivity of magnetic resonance molecular(MR) imaging
      on the basis of the targeting and magnifying effects of biotin-avidin system.
      METHODS: Biotinylated monoclonal antibody HAb18 was prepared, and the number of
      biotin molecules coupled to each antibody molecule was assayed together with the
      binding capacity of the biotinylated antibody. HAb18 was intravenously injected
      into 8 BALB/c nude mice bearing QGY-7723 tumor cells, followed by administration
      of 80 microg avidin as the chaser 24 h later and then Gd-DTAP-streptavidin
      injection after another 30 min. MR imaging was performed before and 10, 30, 60
      min and 3, 6, 12, and 24 h after the injection of the contrast agents. All the
      images were obtained using SE T(1)-weighted imaging sequence. The enhancement
      time course of the tumor, liver and muscles were determined by measuring the
      signal intensity (SI) in the region of interest in the tumor, and the enhancement
      ratio and contrast-to-noise ratio (CNR) of the tumor also calculated. RESULTS: On
      average, 20 biotin molecules conjugated with each monoclonal antibody molecule,
      and the immunoactivity of the biotinylated antibody reached 91%. The SI of the
      tumor increased slowly and peaked at 6 h after injection of Gd-DTPA-streptavidin,
      when the enhancement ratio and CNR of the tumor were significantly higher then
      those measured on other time points. The SI of the liver reached the maximum
      value at 6 h after injection of the contrast agent, and then declined to the non
      enhanced level 12 h after injection. The SI of the muscle exhibited no
      significant difference after enhancement. CONCLUSIONS: In targeted MR of the
      tumor, biotin-avidin system produces specific and prolonged enhancement of the
      signals, but blood pool effect of Gd-DTPA-streptavidin also causes prolonged
      enhancement of the liver.

PMID- 15485784
TI  - [Exogenous mIkappaBalpha gene inhibits the growth of HepG2 heptocellular
      carcinoma cells].
AB  - OBJECTIVE: To observe the expression of mIkappaBalpha, the inhibitor of NFkappaB,
      in HepG2 heptocellular carcinoma cells and the inhibitory effect of mIkappaBalpha
      on HepG2 cell growth. METHODS: The adenovirus containing mIkappaBalpha or the
      packaging vector were harvested from 293 packaging cells to infect HepG2 cells,
      in which the expression of green fluorescence protein (GFP) and mIkappaBalpha
      protein were detected. The plating efficiency and colony-forming ability in soft
      agar were evaluated, cell growth curve was generated and the tumor growth
      observed in nude mice. RESULTS: HepG2 cells infected by the packaged adenovirus
      (HepG2/Adv cells) had positive GFP expression, and those infected by the
      adenovirus containing mIkappaBalpha (HepG2/Ad-mIkappaBalpha cells) showed
      mIkappaBalpha protein expression, as demonstrated by Western blot analysis.
      HepG2/Adv cells exhibited markedly lowered colony-forming ability as compared
      with that of the HepG2/Adv and HepG2 cells, and the latter two cells, but not the
      former cells, could survive in soft agar and form colonies in the shape of
      mulberries. Cell growth curve showed that the Hep G2/Ad-mIkappaBalpha cells had
      also significantly reduced growth rate, but their saturation density in culture
      was comparable with the other two cells. Four weeks after inoculation in nude
      mice, HepG2/Ad-mIkappaBalpha and HepG2/Adv cells showed no significant difference
      in tumorigenicity (80% vs 100%, respectively), but the tumor volume generated by
      the former cells was significantly smaller (P<0.05). CONCLUSION: mIkappaBalpha
      gene can inhibit the growth of HepG2 heptocellular carcinoma cells.

PMID- 15485785
TI  - [Role of pancreatic enzymes in gut injury secondary to trauma/hemorrhagic shock
      in rats].
AB  - OBJECTIVE: To test the hypothesis that pancreatic digestive enzymes are involved
      in trauma/hemorrhagic shock (T/HS)-induced intestinal injury. METHODS: Male
      Sprague-Dawley rats were given pancreatic enzyme inhibitor (6-amidino-2 -naphthyl
      p-guanidinobenzoate dimethanesulfonate, ANGD) intraluminally or intravenously
      after laparotomy (trauma), and then subjected to 90 min of hemorrhagic shock or
      sham shock. Intestinal injury was assessed 3 h after resuscitation with Ringer's
      lactate solution. RESULTS: Histological analysis demonstrated fewer injured villi
      in shock rats with intraluminal ANGD treatment than in those with intravenous
      ANGD administration and control shock rats. Furthermore, intestinal intraluminal
      perfusion of Ringer's lactate solution without ANGD produced a certain degree of
      protection against T/HS-induced intestinal injury, as compared with the rats
      without perfusion. CONCLUSION: Pancreatic proteolytic enzymes in ischemic gut may
      serve as important toxic factors contributing to gut injury following T/HS.

PMID- 15485786
TI  - [Isolation, culture and identification of rat hippocampal neural stem cells].
AB  - OBJECTIVE: To explore the feasibility of the isolation, culture and
      identification of the neural stem cells originated from the hippocampi of
      neonatal rats (1-3 d) and adult rats respectively. METHODS: The neural stem cells
      were isolated from the hippocampi of neonatal and adult rats and cultured in
      serum-free medium containing basic fibroblast growth factor (bFGF), brain-derived
      neurotrophic factor (BDNF) and other growth factors using single-cell cloning
      technique. Immunochemistry was employed to identify the cloned cells and their
      daughter cells as well as mature neural cells differentiated from the cell clone.
      RESULTS: The floating neural spheres obtained by above culture procedures for
      isolated cells from the hippocampi of neonatal and adult rats were positive for
      nestin expression, with the potential for further cloning and capable of
      differentiation into neurons or glial cells, which formed reticular connection
      between the cells and expressed neuron-specific enolase (NSE) and glial
      fibrillary acidic protein (GFAP) respectively. CONCLUSION: The hippocampi of
      neonatal and adult rats contain neural stem cells.

PMID- 15485787
TI  - [A new method for screening mutant yeast strains with green fluorescent protein].
AB  - OBJECTIVE: To establish a fast and simple method for screening mutant yeast
      strains. MATERIALS AND METHODS: Homologous recombination technique was used to
      detect mutant yeast strains in yeast genomic library, with the green fluorescent
      protein gene as the reporter gene in the transposon. RESULTS: The strains that
      emitted green fluorescence were isolated, indicating that the gfp gene was
      inserted into the yeast genome by homologous recombination. CONCLUSION: This
      study established a useful method for functional genome study by homologous
      recombination technique, and provide an alternative for gene therapeutic drug
      development.

PMID- 15485788
TI  - [Bioinformatic analysis of Vibrio parahaemolyticus thermolabile hemolysin gene].
AB  - OBJECTIVE: To carry out bioinformatic analysis of Vibrio parahaemolyticus
      thermolabile hemolysin gene (tlh) obtained by PCR amplification. METHODS: The tlh
      gene amplified by PCR was cloned into the vector pET32a(+) and sequenced,
      followed by analysis of the biological information by with presenting the
      sequences to the websites of bioinformatics on the Internet. RESULTS AND
      CONCLUSIONS: The sequenced tlh gene (named tlh14-90) was entered into GenBank
      with the accession number of AY289609. Tlh14-90 has a length of 1 257 bp with
      both start and stop codons, having 99% homology with the tlh gene of WP1. Tlh14
      90 is predicted to encode a protein containing 418 amino acids (named TLH14-90,
      with the molecular formula of C(2131)H(3184)N(548)O(649)S(16), molecular weight
      of 47 392.9, and the theoretical PI of 4.92). This protein consists of 4 Cys and
      the contents of Ala, Leu and Asn are 11.0%, 7.4% and 7.2%, respectively, having a
      hydrophobic parameter of -34 calculated using kappa-D method. Predicted as a
      alpha/protein for its secondary structure, TLH14-90 has not been identified for
      its tertiary structure.

PMID- 15485789
TI  - [Surgical procedure improvement to produce rat ischemia-reperfusion injury model
      with intraluminal suture].
AB  - OBJECTIVE: To describe a modified surgical approach to produce rat ischemia
      reperfusion injury model with intraluminal suture. METHODS: After exposure and
      ligation of the common carotid artery (CCA), the left external carotid artery and
      pterygopalatine artery were opened in which a 3-0 nylon suture was introduced
      intraluminally from the distal end of the ligature of the CCA using a scalp
      needle. Reperfusion injury was induced by withdrawal of the suture. RESULTS: The
      length of the suture was about 20.0+/-1.8 mm and the success rate of model
      establishment was nearly 70%. The rats developed typical symptoms and
      pathological manifestations after the surgery. CONCLUSION: This modified surgical
      approach is simple for model establishment and does not require special
      microsurgical skills to ensure the high success rate.

PMID- 15485790
TI  - [Apoptosis and regulation of expressions of apoptosis-related gene Bcl-2 and p53
      induced by selenium dioxide in three leukemia cell lines].
AB  - OBJECTIVE: To investigate the mechanisms underlying the effect of selenium
      dioxide (SeO(2)) on the proliferation, apoptosis, and apoptosis-related gene
      expressions of Bcl-2 and p53 in 3 leukemia cell lines NB4, K562 and HL-60.
      METHODS: The three leukemia cell lines were treated with 3, 10 and 30 mmol/L
      SeO(2) and apoptosis detected by flow cytometry and analysis of p53 and Bcl-2
      expressions. RESULTS: SeO(2) at 10 and 30 mmol/L could inhibit the proliferation
      of three leukemia cell lines. SeO(2) treatment at 30 mmol/L for 48 h induced an
      apoptosis rate of 54.0 %, 46.5 %, 49.6 % in NB4, K562, and HL-60 cells
      respectively, and down-regulated Bcl-2 expression in NB4 and K562 but not in HL
      60 cells. CONCLUSION: SeO(2) can induce apoptosis in NB4, K562 and HL-60 leukemia
      cells, involving the down-regulation of Bcl-2 and up-regulation of p53.

PMID- 15485791
TI  - [Construction of a three-dimensional human angiogenesis model in vitro for
      antiangiogenic drug selection].
AB  - OBJECTIVE: To develop a simple human angiogenesis model that simulates all the
      critical steps of the angiogenic process for screening antiangiogenic substances.
      METHODS: Human umbilical vein endothelial cells (HUVECs) were sandwiched into
      three-dimensional collagen gels for culturing to produce the angiogenesis model
      in vitro, on which the antiangiogenic effects of genistein, tyrphostin A23 and
      lavendustin C were assessed. RESULTS: HUVECs had the capacity to repidly form
      highly organized capillary-like structures in this model with uniformity of the
      entire culture, and was easily reproducible. Tyrosine kinase inhibitors,
      genistein, tyrphostin A23 and lavendustin C were found to inhibit the capillary
      tube formation. CONCLUSION: This new human angiogenesis model has proved to be
      simple, responsive, and reproducible for testing potential angiogenic inhibitors,
      and is suitable for screening anti-angiogenic drugs.

PMID- 15485792
TI  - [Association of interleukin-1 gene polymorphism with gastric cancer in a high
      risk area of China].
AB  - OBJECTIVE: To study the difference in the frequencies of interleukin-1B (IL-1)
      +3954, -511, -31 and IL-1RN gene polymorphism between gastric cancer patients and
      normal subjects in Shaanxi Province, a high risk area of gastric cancer of China.
      METHODS: The genomic DNA was extracted from the peripheral blood of 169 normal
      subjects and 86 gastric cancer patients in Shaanxi Province. IL-1 polymorphisms
      were analyzed using PCR-restriction fragment length polymorphism (PCR-RFLP).
      RESULTS: T/T genotype frequencies of IL-1 in +3954, -511, -31 and IL-1RN loci
      were similar between gastric cancer patients and normal subjects (x(2) = 0, 0.04,
      0.3 and 0, P>0.05, respectively). CONCLUSION: IL-1 gene polymorphism may be not
      associated with the risk of gastric cancer in this high-risk area.

PMID- 15485793
TI  - [Brain-derived neurotrophin factor inhibits steroid biosynthesis by human
      granulosa-lutein cells].
AB  - OBJECTIVE: To study the effect of brain-derived neurotrophin factor (BDNF) on the
      synthesis of estradiol and progesterone in human granulose-lutein cells (HGLCs)
      and the expression of steroidogenic acute regulatory factor (STAR) mRNA. METHODS:
      HGLCs were obtained from infertile women undergoing ovulation induction for
      fertilization-embryo transfer (IVF-ET) for male or tubal factors. HGLCs were
      cultured in serum-free media 199 for 24 h and treated by BDNF at 25, 50 and 100
      ng/ml. Radio immunoassay (RIA) was used to examine the concentration of estradiol
      and progesterone, and reverse transcriptional PCR (RT-PCR) employed to detect the
      expression of STAR mRNA after treatment with BDNF at the concentrations of 25, 50
      and 100 ng/ml. RESULTS: BDNF significantly inhibited the production of
      progesterone (P(4)) in the culture media of HGLCs in a dose-dependent manner.
      BDNF did not change the level of 17beta-estradiol (E(2)), but decreased the
      expression of STAR mRNA dose-dependently. CONCLUSIONS: BDNF can inhibit the
      synthesis of P(4) in HGLCs and regulate ovarian steroidogenesis. BDNF may inhibit
      HGLCs from producing P(4) by decreasing the transcription level of STAR gene in
      human ovary, and plays an important role in luteal regression.

PMID- 15485794
TI  - [Endovascular embolization for traumatic carotid-cavernous fistula].
AB  - OBJECTIVE: To evaluate the choice of approaches, surgical techniques and clinical
      outcome of endovascular embolization for treating traumatic carotid cavernous
      fistula (TCCF). METHODS: A retrospective analysis of 119 patients with TCCF was
      conducted, in whom totally 128 embolizations were performed. In these procedures,
      the femoral artery approach was adopted in 112 cases, femoral vein approach in 5
      cases, and superior ophthalmic vein approach in 2 cases. For the embolization
      materials, balloons were used in 101 cases, microcoils in 13 cases, both
      materials in 2 cases, and lyophilized dura mater in 3 cases. After the
      embolization procedures, 110 patients were followed-up for 3 months to 10 years,
      and 29 patients reexamined with angiography. RESULTS: Successful embolization for
      TCCF in a single procedure was achieved in 111 cases, and failure occurred due to
      balloon leakage in 8 cases, all embolized successfully in a second attempt. The
      total success rate was 100% in these cases, with a rate of internal carotid
      artery patency of 90.8% (108/119). No perioperative mortality or complication
      occurred, nor was TCCF recurrence seen during the follow-up. CONCLUSIONS: In
      general, TCCF can be successfully treated by balloon embolization via the femoral
      artery, while microcoil embolization has better performance for small fistula.
      Embolization can be done through venous approach when the internal carotid artery
      is ligated or occluded, and no procedure should be performed at the convenient
      expense of the internal carotid artery. Right choices of the approaches and
      embolization materials are key to the success of the procedure.

PMID- 15485795
TI  - [Evaluation of non-invasive indices for liver histology in patients with chronic
      hepatitis B].
AB  - OBJECTIVE: To assess the correlation of routine blood and serum biochemical
      indices with liver histology, and identify the sensitive non-invasive ones
      indicative of liver inflammation and fibrosis in patients with chronic hepatitis
      B. METHODS: A total of 252 patients were enrolled in this retrospective analysis.
      The indices including the patients' age, gender, serum alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), albumin, globulin, total bilirubin,
      prothrombin time (PT) and its activity (PTA), WBC, and platelet count were
      analyzed statistically. RESULTS: The status of liver inflammation was correlated
      to patients' routine blood indices (P<0.05). Serum AST, total bilirubin, WBC, and
      platelet count was related significantly to the degree of liver inflammation, but
      serum ALT and AST alone did not describe exactly the degree of liver
      inflammation. The status of liver fibrosis was independent of patients' serum
      ALT, but correlated to other routine blood indices (P<0.05). The patients' age,
      serum AST, total bilirubin and platelet count had significant relation to the
      stage of liver fibrosis, and the age, blood PT, total bilirubin and platelet
      count were significant relevant indices for early liver cirrhosis, and their
      sensitivity, specificity, positive predictive value, negative predictive value
      and accuracy were 31.5%, 94.4%, 60.7%, 83.3% and 80.7%, respectively.
      CONCLUSIONS: Single examination of serum ALT and AST does not help much to
      predict the status of liver test in patients with chronic hepatitis B. Serum AST,
      total bilirubin, WBC and platelet count are associated with the degree of liver
      inflammation. The patients' age, serum total bilirubin, AST and platelet count
      are relevant indices for liver fibrosis, and patients' age, serum total
      bilirubin, PT, and platelet count provide valuable assistance in confirmation of
      early liver cirrhosis with high specificity, but not so for screening purpose.

PMID- 15485796
TI  - [Diagnostic value of 99mTc-MIBI brain SPECT for brain glioma].
AB  - OBJECTIVE: To evaluate the value of (99m)Tc-MIBI brain single-photon emission
      computerized tomography (SPECT) in diagnosis of glioma. METHODS: Fifty-nine
      patients with glioma, 6 with brain abscess and 9 healthy controls underwent
      (99m)Tc-MIBI brain SPECT, and the diagnostic indices such as the sensitivity,
      specificity and accuracy were calculated. The tumor to non-tumor (T/NT) ratios
      were calculated according to the region of interest (ROI) and compared between
      the glioma group, healthy control group and brain abscess group by t test.
      RESULTS: Among the 59 cases of glioma, 51 showed positive results in (99m)Tc-MIBI
      SPECT, along with one of the healthy controls and 4 of brain abscess patients.
      The sensitivity, specificity and accuracy of the diagnosis were 86.4%, 66.7% and
      82.4%, respectively. The T/NT ratio of brain glioma group was 2.6+/-1.2,
      significantly higher than that of normal group (t=3.6199, P<0.001) and brain
      abscess group (t=2.1327, P<0.05). CONCLUSION: (99m)Tc-MIBI brain SPECT is
      sensitive for diagnosis of brain glioma, and can distinguish malignant from
      benign lesions effectively.

PMID- 15485797
TI  - [Risk factors of acute rejection in sensitized kidney transplant recipients].
AB  - OBJECTIVE: To identify the risk factors of acute rejection in sensitized
      recipients undergoing kidney transplantation. METHODS: The clinical data of 102
      sensitized kidney transplant recipients were retrospectively analyzed to evaluate
      the incidence of acute rejection in relation to panel reactive antibodies (PRA),
      amino acid residual match, postoperative elevation of PRA level and cytokine
      genotypes. RESULTS: During the follow-up, acute rejection occurred in totally 33
      patients, and the incidence was higher in the recipients with high tumor necrosis
      factor (TNF)-alpha or high interleukin (IL)-10 producer genotype than in those
      with low TNF-alpha or low/intermediate IL-10 producer genotype (53.1%, 55.0% vs
      22.8%, 20.9%, P(18)0.01 respectively). Acute rejection was even more frequent in
      the recipients with both high TNF-alpha and high/intermediate IL-10 producer
      genotypes than in those with low TNF-alpha and IL-10 producer genotype (66.7% vs
      10.2%, P<0.01). No relations were found between TGF-beta1, IL-6, IFN-gamma gene
      polymorphisms and the incidence of acute rejection. The incidence in the
      recipients with PRA level of more than 40% was also higher than those with lower
      PRA level (<20%, 53.3% vs 22.7%, P<0.05), and the amino acid residual mismatch
      with 3-4 MM was responsible for a higher incidence in comparison with a mismatch
      with 0-1 MM (75.0% vs 24.1%, P<0.01). Postoperative elevation of PRA level also
      increased the risk of acute rejection (45.4% vs 22.4%, P<0.01). CONCLUSION: TNF
      alpha, IL-10 gene polymorphism, PRA, amino acid residual mismatch, and increased
      postoperative PRA level may significantly influence acute rejection in sensitized
      kidney transplantation recipient, and preoperative evaluation of these factors
      may benefit the designing of immunosuppressive protocols for these patients.

PMID- 15485798
TI  - [Therapeutic effects of strontium-89 against osseous metastases of lung cancer:
      analysis of 126 cases].
AB  - OBJECTIVE: To investigate the therapeutic effects of strontium-89 against osseous
      metastases of lung cancer. METHODS: A total of 126 patients with osseous
      metastases of lung cancer received strontium-89 treatment ((89)SrCl(2)) at the
      dose of 148 MBq given through a single intravenous injection. The analgesic
      effect was evaluated by the changes in the degree, frequency and scores of the
      pain, and the therapeutic effect assessed by observing the changes in the number
      and volume of osseous lesions after therapy and compared between different
      pathological types of lung cancer by Ka-square test. RESULTS: Within 6 months
      after the injection, the total pain relief rate was 70.6% (89/126), including 25
      (19.8%) cases with pain vanished, suggesting significant alleviation of the pain
      intensity by the treatment (u=5.361, P<0.01). The frequency of pain was reduced
      in 78.6% (99/126) of the cases (u=4.589, P<0.01), and the average score of pain
      decreased significantly from 7.54+/-3.29 to 4.19+/-4.38 (t=6.865, P<0.001). The
      number and size of lesions decreased by more than 25% in 57 cases, showing a
      total efficacy rate of 45.2% (57/126). No significant difference was noted in the
      therapeutic effects among the 4 pathological types of lung cancer (P>0.05).
      CONCLUSIONS: Strontium-89 is effective for pain relief and tumor focus
      confinement in osseous metastases of lung cancer. No significant difference has
      been found in its effect between 4 different pathological types of lung cancer.

PMID- 15485799
TI  - [Survey of psychological health of parents of children with malignant tumor].
AB  - OBJECTIVE: To understand the psychological problems of parents of children with
      malignant tumor so as to provide them with adequate psychological healthcare
      service. METHODS: A questionnaire-based survey was conducted in 68 parents of
      children with malignant tumor using an internationally standard anxiety scale.
      RESULTS: The 68 parents had a mean score of 44.68+/-11.26 for the scale with
      6.42+/-2.25 anxiety symptoms on average. The average anxiety score of the mothers
      was 58.38+/-8.85, and 53.30+/-9.17 for the fathers, showing obviously difference
      (P<0.05). The average anxiety score of the parents with positive attitudes for
      treatment was 55.07+/-8.91, and that for the parents who gave up treatment for
      economic reasons was 66.71+/-4.50, with also significant difference (P<0.001).
      CONCLUSION: The parents of children with malignancies almost invariably show
      anxiety symptom of different degrees, which can be attributed to their gender and
      economic status.

PMID- 15485800
TI  - [Pneumatic lithotripsy under ureteroscope for pyonephrosis due to calculus
      obstruction].
AB  - OBJECTIVE: To summarize the experiences of pneumatic lithotripsy under
      ureteroscope for pyonephrosis due to calculus obstruction. METHODS: Twelve
      patients with pyonephrosis due to calculus obstruction were treated using
      endoscopic manipulation such as ureteroscopy, pneumatic lithotripsy and
      indwelling double J catheter. RESULTS: In the 12 cases, the ureteral calculi were
      cleared after one treatment in 10 cases, and the other 2 cases were cured by
      additional extracorporeal shock-wave lithotomy performed 1 to 2 weeks later.
      CONCLUSION: Ureteroscopic manipulation is safe, minimally invasive and effective
      for the treatment of pyonephrosis due to calculus obstruction.

PMID- 15485801
TI  - [Three-dimensional ultrasound evaluation of the efficacy and safety of single
      dose systemic or local methotrexate injection for tubal pregnancy].
AB  - OBJECTIVE: To compare the efficacy and safety of single-dose systemic and local
      injection of methotrexate (MTX) in the treatment of tubal pregnancy (TP).
      METHODS: The systemic group included 127 women with TP who received a single-dose
      MTX of 50 mg/m(2) given by intramuscular injection, and the local group included
      118 women receiving single-dose MTX of 100 mg via local injection guided by three
      dimensional (3D) ultrasound. The volume of ectopic masses and blood beta-human
      chorionic gonadotropin (beta-HCG) were measured before and after MTX
      administration. The TP was detected by 3D images reconstructed 3 months after MTX
      administration. RESULTS: The success rate of treatment was 100% in the local
      group, significantly higher than that of 91.34% in the systemic group. After the
      first week of MTX injection, the speed of the ectopic mass resolution was 0.85+/
      0.04 cm(3)/d and 0.47+/-0.03 cm(3)/d in systemic group and local group
      respectively (P<0.05), and the time of the ectopic mass resolution was 27.66+/
      12.77 d and 32.62+/-12.75 d, respectively (P<0.01). The rate of tubal deformity
      in the local group was significantly lower than that in the systemic group.
      CONCLUSION: Local injection of MTX under ultrasound guidance is safe, efficient
      and reliable for conservative management of unruptured TP, which is superior to
      systemic injection.

PMID- 15485802
TI  - [Neural stem cell transplantation and postoperative management: report of 70
      cases].
AB  - OBJECTIVE: To review the operations of neural stem cells transplantation in
      patients with brain trauma or spinal cord injury and their postoperative
      management. METHODS: A retrospective analysis was conducted in 70 cases of brain
      trauma or paraplegia treated with neural stem cell transplantation in the recent
      two years. RESULTS: All patients were smoothly discharged except for 3 who
      developed intracranial infection corrected with antibiotics via the vertebral
      canal. Another 3 patients with total loss of sexual function after spinal cord
      injury for over 1 year recovered sexual function after neural stem cell
      transplantation. CONCLUSION: Neural stem cell transplantation can promote the
      functional recovery of the brain and spinal cord in patients with brain trauma or
      spinal cord injury. Proper postoperative management for the patients is crucial
      to ensure favorable prognosis.

PMID- 15485803
TI  - [Intensive care and treatment of severe ovarian hyperstimulation syndrome].
AB  - OBJECTIVE: To investigate the clinical manifestations, pathogenesis and treatment
      of severe ovarian hyperstimulation syndrome (OHSS). METHODS: The clinical data of
      20 OHSS patients were analyzed retrospectively. RESULTS: Severe OHSS occurred
      after controlled ovarian hyperstimulation for superovulation. The major
      manifestations of OHSS included abdominal distension, nausea, ascites,
      hydrothorax, oliguria, concentrated blood, acid-base and electrolytes,
      disturbance, azotemia, thrombosis etc., which could be controlled by volume
      expansion with albumin, low-molecular-weight dextran, 6% Haes, abdominal and
      thoracic drainages or even early pregnancy termination. CONCLUSION: Preventive
      measure of OHSS is very important, and the patients must be treated timely and
      correctly once OHSS occurs.

PMID- 15485804
TI  - Substrate specificity and kinetic mechanism of mammalian G9a histone H3
      methyltransferase.
AB  - Lysine-specific murine histone H3 methyltransferase, G9a, was expressed and
      purified in a baculovirus expression system. The primary structure of the
      recombinant enzyme is identical to the native enzyme. Enzymatic activity was
      favorable at alkaline conditions (>pH 8) and low salt concentration and virtually
      unchanged between 25 and 42 degrees C. Purified G9a was used for substrate
      specificity and steady-state kinetic analysis with peptides representing un- or
      dimethylated lysine 9 histone H3 tails with native lysine 4 or with lysine 4
      changed to alanine (K4AK9). In vitro methylation of the H3 tail peptide resulted
      in trimethylation of Lys-9 and the reaction is processive. The turnover number
      (k(cat)) for methylation was 88 and 32 h(-1) on the wild type and K4AK9 histone
      H3 tail, respectively. The Michaelis constants for wild type and K4AK9
      ((K(m)(pep))) were 0.9 and 1.0 microM and for S-adenosyl-L-methionine
      (K(m)(AdoMet)) were 1.8 and 0.6 microM, respectively. Comparable kinetic
      constants were obtained for recombinant histone H3. The conversion of K4AK9 di-
      to trimethyl-lysine was 7-fold slower than methyl group addition to unmethylated
      peptide. Preincubation studies showed that G9a-AdoMet and G9a-peptide complexes
      are catalytically active. Initial velocity data with peptide and S-adenosyl-L
      methionine (AdoMet) and product inhibition studies with S-adenosyl-L-homocysteine
      were performed to assess the kinetic mechanism of the reaction. Double reciprocal
      plots and preincubation studies revealed S-adenosyl-L-homocysteine as a
      competitive inhibitor to AdoMet and mixed inhibitor to peptide. Trimethylated
      peptides acted as a competitive inhibitor to substrate peptide and mixed
      inhibitor to AdoMet suggesting a random mechanism in a Bi Bi reaction for
      recombinant G9a where either substrate can bind first to the enzyme, and either
      product can release first.

PMID- 15485805
TI  - Endothelial lipase modulates monocyte adhesion to the vessel wall. A potential
      role in inflammation.
AB  - Endothelial lipase (EL), a new member of the lipoprotein lipase gene family,
      plays a central role in high density lipoprotein metabolism. Previous studies
      indicated that EL is expressed in endothelial cells, macrophages, and smooth
      muscle cells in atherosclerotic lesions in human coronary arteries. However, the
      functional role of EL in the local vessel wall remains obscure. In this study, we
      evaluated the ability of EL to modulate monocyte adhesion to the endothelial cell
      surface. EL mRNA and protein levels were markedly increased in tissues of the
      mouse model of inflammation induced by lipopolysaccharide injection. Adhesion
      assays in vitro revealed that overexpression of EL in COS7 or Pro5 cells enhanced
      monocyte bindings to the EL-expression cells. Heparin or heparinase treatment
      inhibited EL-mediated increases of monocyte adhesion in a dose-dependent manner.
      Moreover, ex vivo adhesion assays revealed that the number of adherent monocytes
      on aortic strips was significantly increased in EL transgenic mice and decreased
      in EL knock-out mice as compared with wild-type mice. These results suggest that
      EL on the endothelial cell surface can promote monocyte adhesion to the vascular
      endothelium through the interaction with heparan sulfate proteoglycans. Thus, the
      up-regulation of EL by inflammatory stimuli may be involved in the progression of
      inflammation.

PMID- 15485806
TI  - Recruitment of thyroid hormone receptor/retinoblastoma-interacting protein 230 by
      the aryl hydrocarbon receptor nuclear translocator is required for the
      transcriptional response to both dioxin and hypoxia.
AB  - The aryl hydrocarbon receptor nuclear translocator/hypoxia-inducible factor
      (ARNT/HIF-1 beta) mediates an organism's response to various environmental cues,
      including those to chemical carcinogens, such as 2,3,7,8-tetrachlorodibenzo-rho
      dioxin (TCDD or dioxin), via its formation of a functional transcription factor
      with the ligand activated aryl hydrocarbon receptor (AHR). Similarly, tissue
      responses to hypoxia are largely mediated through the HIF-1 heterodimeric
      transcription factor, comprising hypoxia-inducible factor-1 alpha (HIF-1 alpha)
      and ARNT. The latter response is essential for a metabolic switch from oxidative
      phosphorylation to glycolytic anaerobic metabolism as well as for angiogenesis
      and has been implicated as necessary for growth in many solid tumors. In this
      report, we demonstrate that the thyroid hormone receptor/retinoblastoma
      interacting protein 230 (TRIP230) interacts directly with ARNT and is essential
      for both hypoxic and TCDD-mediated transcriptional responses. We initially
      identified TRIP230 as an ARNT-interacting protein in a yeast two-hybrid assay
      screen. This interaction was confirmed in mammalian cell systems using co
      immunoprecipitation and in mammalian two-hybrid assays. Furthermore, TRIP230
      could be recorded at sites of activated transcription of either TCDD- or hypoxia
      inducible genes in a stimulus-dependent fashion by chromatin immunoprecipitation
      analysis. Finally, using single-cell microinjection and RNA interference assays,
      we demonstrate that TRIP230 is indispensable for TCDD- and hypoxia-dependent gene
      transcription.

PMID- 15485807
TI  - Three-dimensional structure of P-glycoprotein: the transmembrane regions adopt an
      asymmetric configuration in the nucleotide-bound state.
AB  - Multidrug resistance of cancer cells and pathogens is a serious clinical problem.
      A major factor contributing to drug resistance in cancer is the over-expression
      of P-glycoprotein, a plasma membrane ATP-binding cassette (ABC) drug efflux pump.
      Three-dimensional structural data with a resolution limit of approximately 8 A
      have been obtained from two-dimensional crystals of P-glycoprotein trapped in the
      nucleotide-bound state. Each of the two transmembrane domains of P-glycoprotein
      consists of six long alpha-helical segments. Five of the alpha-helices from each
      transmembrane domain are related by a pseudo-2-fold symmetry, whereas the sixth
      breaks the symmetry. The two alpha-helices positioned closest to the (pseudo-)
      symmetry axis at the center of the molecule appear to be kinked. A large loop of
      density at the extracellular surface of the transporter is likely to correspond
      to the glycosylated first extracellular loop, whereas two globular densities at
      the cytoplasmic side correspond to the hydrophilic, nucleotide-binding domains.
      This is the first three-dimensional structure for an intact eukaryotic ABC
      transporter. Comparison with the structures of two prokaryotic ABC transporters
      suggests significant differences in the packing of the transmembrane alpha
      helices within this protein family.

PMID- 15485808
TI  - H3 domain of syntaxin 1A inhibits KATP channels by its actions on the
      sulfonylurea receptor 1 nucleotide-binding folds-1 and -2.
AB  - The ATP-sensitive potassium (K(ATP)) channel in pancreatic islet beta cells
      consists of four pore-forming (Kir6.2) subunits and four regulatory sulfonylurea
      receptor (SUR1) subunits. In beta cells, the K(ATP) channel links intracellular
      metabolism to the dynamic regulation of the cell membrane potential that triggers
      insulin secretion. Syntaxin 1A (Syn-1A) is a SNARE protein that not only plays a
      direct role in exocytosis, but also binds and modulates voltage-gated K(+) and
      Ca(2+) channels to fine tune exocytosis. We recently reported that wild type Syn
      1A inhibits rat islet beta cell K(ATP) channels and binds both nucleotide-binding
      folds (NBF-1 and NBF-2) of SUR1. However, wild type Syn-1A inhibition of rat
      islet beta cell K(ATP) channels seems to be mediated primarily via NBF-1. During
      exocytosis, Syn-1A undergoes a conformational change from a closed form to an
      open form, which would fully expose its active domain, the C-terminal H3 domain.
      Here, we show that the constitutively open form Syn-1A mutant (L165A/E166A) has a
      similar affinity to NBF-1 and NBF-2 as wild type Syn-1A and was equally effective
      in inhibiting the K(ATP) channels of rat pancreatic beta cells and a cell line
      (BA8) stably expressing SUR1/Kir6.2. Although dialysis of NBF-1 into BA8 and
      islet beta cells effectively blocked wild type and open form Syn-1A inhibition of
      the K(ATP) current, NBF-2 was also effective in blocking the open form Syn-1A
      inhibition. This prompted us to examine the specific domains within Syn-1A that
      would mediate its action on the K(ATP) channels. The C-terminal H3 domain of Syn
      1A (Syn-1A-H3), but not the N-terminal H(ABC) domain (Syn-1A-H(ABC)), binds the
      SUR1 protein of BA8 cells, causing an inhibition of K(ATP) currents, and this
      inhibition was mediated via both NBF-1 and NBF-2. It therefore appears that the
      H3 domain of Syn-1A is the putative domain, which binds SUR1, but its distinct
      actions on the NBFs may depend on the conformation of Syn-1A occurring during
      exocytosis.

PMID- 15485809
TI  - Chondroitin synthase 1 is a key molecule in myeloma cell-osteoclast interactions.
AB  - There is a symbiotic relationship between continued growth and proliferation of
      myeloma cells and the bone destructive process. It has been shown in animal
      models that blocking bone destruction can result in decreased myeloma tumor
      burden. Osteoclasts are bone destroying cells found in the bone marrow, and their
      significance in myeloma is supported by recent findings that osteoclasts alone
      can support sustained survival and proliferation of purified primary myeloma
      cells in ex vivo co-cultures. However, molecular mechanisms associated with
      interactions between myeloma cells and osteoclasts remain unclear. Here, we show
      that when myeloma plasma cells are co-cultured with osteoclasts, chondroitin
      synthase 1 (CHSY1) is the most significantly altered soluble, secreted protein
      present in the conditioned medium. RNA interference experiments with CHSY1 small
      interfering RNA (siRNA) reduced the amount of CHSY1 in the co-culture conditioned
      medium, and this was associated with a 6.25-fold increase in apoptotic myeloma
      cells over control co-cultures. CHSY1 contains a Fringe domain, and Fringe is
      well known for its regulation of Notch signaling via its DDD motif. And
      interestingly, Fringe domain in CHSY1 has this DDD motif. Shortly after co
      culture with osteoclasts, we found that the Notch2 receptor was activated in
      myeloma cells but Notch1 was not. Activation of Notch2 was down-regulated by
      CHSY1 siRNA treatment. Modulating Notch signaling by CHSY1 via its DDD motif
      provides new insight into mechanisms of the interactions between myeloma cells
      and their bone marrow microenvironment. Targeting this interaction could shed
      light on treatment of myeloma, which is currently incurable.

PMID- 15485810
TI  - Identification of a new member of the phage shock protein response in Escherichia
      coli, the phage shock protein G (PspG).
AB  - The phage shock protein operon (pspABCDE) of Escherichia coli is strongly up
      regulated in response to overexpression of the filamentous phage secretin protein
      IV (pIV) and by many other stress conditions including defects in protein export.
      PspA has an established role in maintenance of the proton-motive force of the
      cell under stress conditions. Here we present evidence for a new member of the
      phage shock response in E. coli. Using transcriptional profiling, we show that
      the synthesis of pIV in E. coli leads to a highly restricted response limited to
      the up-regulation of the psp operon genes and yjbO. The psp operon and yjbO are
      also up-regulated in response to pIV in Salmonella enterica serovar Typhimurium.
      yjbO is a highly conserved gene found exclusively in bacteria that contain a psp
      operon but is physically unlinked to the psp operon. yjbO encodes a putative
      inner membrane protein that is co-controlled with the psp operon genes and is
      predicted to be an effector of the psp response in E. coli. We present evidence
      that yjbO expression is driven by sigma(54)-RNA polymerase, activated by PspF and
      integration host factor, and negatively regulated by PspA. PspF specifically
      regulates only members of the PspF regulon: pspABCDE and yjbO. We found that
      increased expression of YjbO results in decreased motility of bacteria. Because
      yjbO is co-conserved and co-regulated with the psp operon and is a member of the
      phage shock protein F regulon, we propose that yjbO be renamed pspG.

PMID- 15485811
TI  - Human Zwint-1 specifies localization of Zeste White 10 to kinetochores and is
      essential for mitotic checkpoint signaling.
AB  - Chromosome segregation in mitosis is orchestrated by dynamic interaction between
      spindle microtubules and the kinetochore, a multiprotein complex assembled onto
      centromeric DNA of the chromosome. Here we show that Zwint-1 is required and is
      sufficient for kinetochore localization of Zeste White 10 (ZW10) in HeLa cells.
      Zwint-1 specifies the kinetochore association of ZW10 by interacting with its N
      terminal domain. Suppression of synthesis of Zwint-1 by small interfering RNA
      abolishes the localization of ZW10 to the kinetochore, demonstrating the
      requirement of Zwint-1 for ZW10 kinetochore localization. In addition, depletion
      of Zwint-1 affects no mitotic arrest but causes aberrant premature chromosome
      segregation. These Zwint-1-suppressed cells display chromosome bridge phenotype
      with sister chromatids inter-connected. Moreover, Zwint-1 is required for stable
      association of CENP-F and dynamitin but not BUB1 with the kinetochore. Finally,
      our studies show that Zwint-1 is a new component of the mitotic check-point, as
      cells lacking Zwint-1 fail to arrest in mitosis when exposed to microtubule
      inhibitors, yielding interphase cells with multinuclei. As ZW10 and Zwint-1 are
      absent from yeast, we reasoned that metazoans evolved an elaborate spindle
      checkpoint machinery to ensure faithful chromosome segregation in mitosis.

PMID- 15485812
TI  - The DnaK-DnaJ-GrpE chaperone system activates inert wild type pi initiator
      protein of R6K into a form active in replication initiation.
AB  - The plasmid R6K is an interesting model system for investigating initiation of
      DNA replication, not only near the primary binding sites of the initiator protein
      pi but also at a distance, caused by pi -mediated DNA looping. An important
      milestone in the mechanistic analysis of this replicon was the development of a
      reconstituted replication system consisting of 22 different highly purified
      proteins (Abhyankar, M. A., Zzaman, S., and Bastia, D. (2003) J. Biol. Chem. 278,
      45476-45484). Although the in vitro reconstituted system promotes ori gamma
      specific initiation of replication by a mutant form of the initiator called pi*,
      the wild type (WT) pi is functionally inert in this system. Here we show that the
      chaperone DnaK along with its co-chaperone DnaJ and the nucleotide exchange
      factor GrpE were needed to activate WT pi and caused it to initiate replication
      in vitro at the correct origin. We show further that the reaction was relatively
      chaperone-specific and that other chaperones, such as ClpB and ClpX, were
      incapable of activating WT pi. The molecular mechanism of activation appeared to
      be a chaperone-catalyzed facilitation of dimeric inert WT pi into iteron-bound
      monomers. Protein-protein interaction analysis by enzyme-linked immunosorbent
      assay revealed that, in the absence of ATP, DnaJ directly interacted with pi but
      its binary interactions with DnaK and GrpE and with ClpB and ClpX were at
      background levels, suggesting that pi is recruited by protein-protein interaction
      with DnaJ and then fed into the DnaK chaperone machine to promote initiator
      activation.

PMID- 15485813
TI  - Heterogeneous nuclear ribonucleoprotein K enhances insulin-induced expression of
      mitochondrial UCP2 protein.
AB  - The uncoupling protein 2, UCP2, is a member of a family of inner mitochondrial
      membrane ion carriers involved in a host of metabolic processes. UCP2 protein is
      encoded by nuclear genome, but the protein is found exclusively in the
      mitochondria. The heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA
      binding protein involved in many processes that compose gene expression,
      including mRNA processing and translation. The yeast three-hybrid screen revealed
      K protein bound to ucp2 mRNA through sites located in the 3'-untranslated region
      of the transcript. ucp2 mRNA-K protein complexes were associated with polysome
      coated mitochondria. Expression of exogenous K protein augmented the insulin
      induced mitochondrial level of UCP2 protein that was not accompanied by a
      corresponding increase in ucp2 mRNA. These results suggest the insulin stimulates
      translation of ucp2 mRNA in a process that involves K protein.

PMID- 15485814
TI  - The central acidic domain of MDM2 is critical in inhibition of retinoblastoma
      mediated suppression of E2F and cell growth.
AB  - Retinoblastoma (Rb) protein is a paradigm of tumor suppressors. Inactivation of
      Rb plays a critical role in the development of human malignancies. MDM2, an
      oncogene frequently found amplified and overexpressed in a variety of human
      tumors and cancers, directly interacts and inhibits the p53 tumor suppressor
      protein. In addition, MDM2 has been shown to stimulate E2F transactivation
      activity and promote S-phase entry independent of p53, yet the mechanism of which
      is still not fully understood. In this study, we demonstrate that MDM2
      specifically binds to Rb C-pocket and that the central acidic domain of MDM2 is
      essential for Rb interaction. In addition, we show that overexpression of MDM2
      reduces Rb-E2F complexes in vivo. Moreover, the ectopic expression of the wild
      type MDM2, but not mutant MDM2 defective in Rb interaction, stimulates E2F
      transactivation activity and inhibits Rb growth suppression function. Taken
      together, these results suggest that MDM2-mediated inhibition of Rb likely
      contributes to MDM2 oncogenic activity.

PMID- 15485815
TI  - Interleukin-10 induces uteroglobin-related protein (UGRP) 1 gene expression in
      lung epithelial cells through homeodomain transcription factor T/EBP/NKX2.1.
AB  - UGRP1 is a downstream target gene for homeodomain transcription factor
      T/EBP/NKX2.1, which is predominantly expressed in lung epithelial cells, and may
      play an anti-inflammatory role in lung inflammation. To understand the role of
      UGRP1 in inflammation, its expression was investigated in relation to cytokine
      signaling. In vivo experiments using mouse embryonic lung organ culture and
      intranasal administration of interleukin (IL) 10 revealed that constitutive
      expression of Ugrp1 mRNA is enhanced by IL-10. Increase of protein levels was
      also demonstrated by immunohistochemistry using embryonic lungs. This IL-10
      induction of Ugrp1 gene expression occurs at the transcriptional level when
      examined using mouse embryonic lung primary cultures. In human lung NCI-H441
      cells that in contrast to mouse lung cells, do not exhibit constitutive
      expression of the gene, expression of the UGRP1 gene was induced in a rapid and
      stable fashion. Two T/EBP, but not STAT3, binding sites located in the human
      UGRP1 gene promoter are responsible for IL-10 induction of the UGRP1 gene as
      judged by transfection, gel shift, and chromatin immunoprecipitation analyses.
      The IL-10 receptor chains, IL-10R1 and IL-10R2, are expressed in H441 cells,
      however, STAT3 was only weakly activated upon IL-10 treatment. In contrast, STAT3
      was strongly activated when the cells were treated with other cytokines such as
      IL-22 and interferon-beta but UGRP1 expression was not increased. Together these
      results demonstrate that IL-10 induces UGRP1 gene expression in lung epithelial
      cells through a T/EBP/NKX2.1-dependent pathway. The results further suggest that
      UGRP1 might be a target for IL-10 anti-inflammatory activities in the lung.

PMID- 15485816
TI  - Identification of a prostaglandin-responsive element in the Na,K-ATPase beta 1
      promoter that is regulated by cAMP and Ca2+. Evidence for an interactive role of
      cAMP regulatory element-binding protein and Sp1.
AB  - The Na,K-ATPase is a transmembrane protein responsible for maintaining
      electrochemical gradients across the plasma membrane in all mammalian cells, a
      process that is subject to regulation at the transcriptional as well as post
      transcriptional level. Included among physiologic regulators in the kidney are
      prostaglandins. Previously, we demonstrated that prostaglandin E(1) (PGE(1))
      increases the activity and expression of the Na,K-ATPase in Madin-Darby canine
      kidney cells (Taub, M., Borsick, M., Geisel, J., Matlhagela, K., Rajkhowa, T.,
      and Allen, C. (2004) Exp. Cell Res. 299, 1-14; Taub, M. L., Wang, Y., Yang, I.
      S., Fiorella, P., and Lee, S. M. (1992) J. Cell. Physiol. 151, 337-346). In this
      work, we present evidence that transcription of the Na,K-ATPase beta(1) subunit
      is stimulated by PGE(1), an effect that may be mediated through the cAMP and
      Ca(2+) pathways. Transient transfection studies using 5'-deletion mutants of the
      human beta(1) subunit promoter indicated that region -100 to -92 containing the
      sequence AGTCCCTGC (a prostaglandin-responsive element (PGRE)) is required to
      elicit the stimulatory effects of PGE(1), 8-bromo-cAMP, phorbol 12-myristate 13
      acetate, and okadaic acid. Electrophoretic mobility shift assays indicated that
      both the cAMP regulatory element-binding protein (CREB) and Sp1 bind to the PGRE
      present within this region of the beta(1) subunit promoter. The involvement of
      the PGRE and Sp1 sites in regulation by PGE(1) was further confirmed by the
      increased PGE(1) stimulation that was observed following insertion of the PGRE
      into a promoter/luciferase construct containing a portion of a heterologous
      promoter and the fibronectin promoter with four GC boxes. Further evidence
      suggesting an interaction between Sp1 and CREB was obtained from experiments
      conducted with pLuc-MCS-beta 72-167, which contains region -167 to -72 in the
      human beta(1) subunit promoter. The PGE(1) stimulation observed in Madin-Darby
      canine kidney cells transiently transfected with pLuc-MCS-beta 72-167 was reduced
      when the two GC boxes immediately upstream from the PGRE were translocated
      farther upstream. Also consistent with an interaction between CREB and Sp1 are
      the results of our immunoprecipitation studies indicating that CREB co
      immunoprecipitated with Sp1 when an antibody against CREB, Sp1, or the CREB
      binding protein was used.

PMID- 15485817
TI  - The alpha 1 isoform of Na,K-ATPase regulates cardiac contractility and
      functionally interacts and co-localizes with the Na/Ca exchanger in heart.
AB  - The primary objective of this study was to examine the functional role of the
      Na,K-ATPase alpha 1 isoform in the regulation of cardiac contractility. Previous
      studies using knock-out mice showed that the hearts of animals lacking one copy
      of the alpha 1 or alpha 2 isoform gene exhibit opposite phenotypes. Hearts from
      alpha 2(+/-) animals are hypercontractile, whereas those of the alpha 1(+/-)
      animals are hypocontractile. The cardiac phenotype of the alpha 1(+/-) animals
      was unexpected as other studies suggest that inhibition of either isoform
      increases contraction. To help resolve this difference, we have used genetically
      engineered knock-in mice expressing a ouabain-sensitive alpha 1 isoform and a
      ouabain-resistant alpha 2 isoform of the Na,K-ATPase, and we analyzed cardiac
      contractility following selective inhibition of the alpha1 isoform by ouabain.
      Administration of ouabain to these animals and to isolated heart preparations
      selectively inhibits only the activity of the alpha 1 isoform without affecting
      the activity of the alpha 2 isoform. Low concentrations of ouabain resulted in
      positive cardiac inotropy in both isolated hearts and intact animals expressing
      the modified alpha 1 and alpha 2 isoforms. Pretreatment with 10 microm KB-R7943,
      which inhibits the reverse mode of the Na/Ca exchanger, abolished the cardiotonic
      effects of ouabain in isolated wild type and knock-in hearts. Immunoprecipitation
      analysis demonstrated co-localization of the alpha1 isoform and the Na/Ca
      exchanger in cardiac sarcolemma. The alpha 1 isoform co-immunoprecipitated with
      the Na/Ca exchanger and vice versa. These results demonstrate that the alpha 1
      isoform regulates cardiac contractility, and that both the alpha 1 and alpha 2
      isoforms are functionally and physically coupled with the Na/Ca exchanger in
      heart.

PMID- 15485818
TI  - Charged residues at the 2' position of human GABAC rho 1 receptors invert ion
      selectivity and influence open state probability.
AB  - The ability of members of the nicotinicoid superfamily of ligand-gated ion
      channels to selectively conduct anions or cations is critical to their function
      within the central nervous system. Recent work has demonstrated that residues at
      the intracellular end of the second transmembrane domain, between the -3' and 2'
      positions, form the ion selectivity filter of these receptors. In this study, the
      proline residue at the 2' position (Pro-2') at the intracellular end of the
      second transmembrane domain of the gamma-aminobutyric acid type C rho 1 subunit
      was mutated to glutamate (rho 1P2'E) and arginine (rho 1P2'R). Dilution potential
      experiments indicated that the charge selectivity of the rho 1P2'E receptor
      channels had been inverted, with the channels now becoming predominantly cation
      selective, indicating the ability of negatively charged residues at this 2'
      position to control charge selectivity. The mutation was also seen to have
      significantly decreased agonist potency and intrinsic efficacy. In contrast, the
      rho 1P2'R receptor channels were anion-selective but were now found to be
      constitutively open with high holding currents (inhibited by low gamma
      aminobutyric acid doses and the competitive antagonist, 1,2,5,6
      tetrahydropyridine-4-yl)methylphosphinic acid alone) and increased agonist
      activity. Hill coefficients of both mutants were decreased, but competitive
      antagonist studies indicated that their binding sites were not significantly
      affected.

PMID- 15485819
TI  - The integrin-linked kinase regulates cell morphology and motility in a rho
      associated kinase-dependent manner.
AB  - The integrin-linked kinase (ILK) is a multidomain focal adhesion protein
      implicated in signal transmission from integrin and growth factor receptors. We
      have determined that ILK regulates U2OS osteosarcoma cell spreading and motility
      in a manner requiring both kinase activity and localization. Overexpression of
      wild-type (WT) ILK resulted in suppression of cell spreading, polarization, and
      motility to fibronectin. Cell lines overexpressing kinase-dead (S343A) or
      paxillin binding site mutant ILK proteins display inhibited haptotaxis to
      fibronectin. Conversely, spreading and motility was potentiated in cells
      expressing the "dominant negative," non-targeting, kinase-deficient E359K ILK
      protein. Suppression of cell spreading and motility of WT ILK U2OS cells could be
      rescued by treatment with the Rho-associated kinase (ROCK) inhibitor Y-27632 or
      introduction of dominant negative ROCK or RhoA, suggesting these cells have
      increased RhoA signaling. Activation of focal adhesion kinase (FAK), a negative
      regulator of RhoA, was reduced in WT ILK cells, whereas overexpression of FAK
      rescued the observed defects in spreading and cell polarity. Thus, ILK-dependent
      effects on ROCK and/or RhoA signaling may be mediated through FAK.

PMID- 15485820
TI  - Tandem promoters and developmentally regulated 5'- and 3'-mRNA untranslated
      regions of the mouse Scn5a cardiac sodium channel.
AB  - The SCN5A gene encodes a voltage-sensitive sodium channel expressed in cardiac
      and skeletal muscle. Coding region mutations cause cardiac sudden death syndromes
      and conduction system failure. Polymorphisms in the 5'-sequence adjacent to the
      SCN5A gene have been linked to cardiac arrhythmias. We identified three
      alternative 5'-splice variants (1A, 1B, and 1C) of the untranslated exon 1 and
      two 3'-variants in the murine Scn5a mRNA. Two of the exon 1 isoforms (1B and 1C)
      were novel when compared with the published human and rat SCN5A sequences.
      Quantitative real time PCR results showed that the abundance of the isoforms
      varied during cardiac development. The 1A, 1B, and 1C mRNA splice variants
      increased 7.8 +/- 1.7-fold (E1A), 6.0 +/- 1.0-fold (E1B), and 20.6 +/- 3.7-fold
      (E1C) from fetal to adult heart, respectively. Promoter deletion and luciferase
      reporter gene analysis using cardiac and skeletal muscle cell lines demonstrated
      a pattern of distinct cardiac-specific enhancer elements associated with exons 1A
      and 1C. In the case of exon 1C, the enhancer element appeared to be within the
      exon. A 5'-repressor preceded each cardiac enhancer element. We concluded that
      the murine Na(+) channel has both 5'- and 3'-untranslated region mRNA variants
      that are developmentally regulated and that the promoter region contains two
      distinct cardiac-specific enhancer regions. The presence of homologous human
      splicing suggests that that these regions may be fruitful new areas of study in
      understanding cardiac sodium channel regulation and the genetic susceptibility to
      sudden death.

PMID- 15485821
TI  - Glyceraldehyde-3-phosphate dehydrogenase interacts with Rab2 and plays an
      essential role in endoplasmic reticulum to Golgi transport exclusive of its
      glycolytic activity.
AB  - Rab2 requires atypical protein kinase C iota/lambda (aPKC iota/lambda) to promote
      vesicle formation from vesicular tubular clusters (VTCs). The Rab2-generated
      vesicles are enriched in recycling proteins suggesting that the carriers are
      retrograde-directed and retrieve transport machinery back to the endoplasmic
      reticulum. These vesicles also contained the glycolytic enzyme glyceraldehyde-3
      phosphate dehydrogenase (GAPDH). We have previously established that GAPDH is
      required for membrane transport between the endoplasmic reticulum and the Golgi
      complex. Moreover, GAPDH is phosphorylated by aPKC iota/lambda and binds to the
      aPKC iota/lambda regulatory domain. In this study, we employed a combination of
      in vivo and in vitro assays and determined that GAPDH also interacts with Rab2.
      The site of GAPDH interaction was mapped to Rab2 residues 20-50. In addition to
      its glycolytic function, GAPDH has multiple intracellular roles. However, the
      function of GAPDH in the early secretory pathway is unknown. One possibility is
      that GAPDH ultimately provides energy in the form of ATP. To determine whether
      GAPDH catalytic activity was critical for transport in the early secretory
      pathway, a conservative substitution was made at Cys-149 located at the active
      site, and the mutant was biochemically characterized in a battery of assays.
      Although GAPDH (C149G) has no catalytic activity, Rab2 recruited the mutant
      protein to membranes in a quantitative binding assay. GAPDH (C149G) is
      phosphorylated by aPKC iota/lambda and binds directly to Rab2 when evaluated in
      an overlay binding assay. Importantly, VSV-G transport between the ER and Golgi
      complex is restored when an in vitro trafficking assay is performed with GAPDH
      depleted cytosol and GAPDH (C149G). These data suggest that GAPDH imparts a
      unique function necessary for membrane trafficking from VTCs that does not
      require GAPDH glycolytic activity.

PMID- 15485822
TI  - Toll-like receptor 9 regulates tumor necrosis factor-alpha expression by
      different mechanisms. Implications for osteoclastogenesis.
AB  - CpG oligodeoxynucleotides (CpG-ODNs), mimicking bacterial DNA, stimulate
      osteoclastogenesis via Toll-like receptor 9 (TLR9) in receptor activator of NF
      kappa B ligand (RANKL)-primed osteoclast precursors. This activity is mediated
      via tumor necrosis factor (TNF)-alpha induction by CpG-ODN. To further reveal the
      role of the cytokine in TLR9-mediated osteoclastogenesis, we compared the ability
      of CpG-ODN to induce osteoclastogenesis in two murine strains, BALB/c and
      C57BL/6, expressing different TNF-alpha alleles. The induction of
      osteoclastogenesis and TNF-alpha release by CpG-ODN was by far more noticeable in
      BALB/c-derived than in C57BL/6-derived osteoclast precursors. Unexpectedly, as
      revealed by Northern analysis, CpG-ODN induction of TNF-alpha mRNA increase was
      more efficient in C57BL/6-derived cells. The cytokine transcript abundance was
      increased due to both increased message stability and rate of transcription. The
      difference between the two cell types was the result of a higher transcription
      rate in CpG-ODN-induced C57BL/6-derived cells caused by a single nucleotide
      polymorphism in kappa B2a site within the TNF-alpha promoter sequence. CpG-ODN
      enhanced the rate of the cytokine translation in BALB/c-derived cells. Thus, CpG
      ODN modulated both transcription and translation of TNF-alpha. The induction of
      transcription was more evident in C57BL/6-derived cells, while the induction of
      translation took place only in BALB/c-derived osteoclast precursors. Altogether
      the cytokine was induced to a larger extent in BALB/c-derived osteoclast
      precursors, consistent with the increased CpG-ODN osteoclastogenic effect in
      these cells.

PMID- 15485823
TI  - Cooperative interaction between the basic helix-loop-helix transcription factor
      dHAND and myocyte enhancer factor 2C regulates myocardial gene expression.
AB  - Cardiac-restricted transcription factors dHAND and myocyte enhancer factor 2C are
      expressed in the developing heart and activate several cardiac promoters.
      However, their regulatory mechanisms are still to be understood. To elucidate
      their exact regulatory functions, we have developed an RNA interference strategy
      to specifically inhibit dHAND and myocyte enhancer factor 2C protein production
      in H9c2 cells, which are derived from rat embryonic heart. Expression of
      endogenous cardiac genes atrial natriuretic peptide and alpha-myosin heavy chain
      was down-regulated in H9c2 cells lacking both dHAND and myocyte enhancer factor
      2C, indicating that these factors are required for the maintenance of the cardiac
      genetic program. Consistent with these, expression of atrial natriuretic peptide
      and alpha-myosin heavy chain was up-regulated in H9c2 cells, which overexpressed
      dHAND and myocyte enhancer factor 2C. In addition, dHAND and myocyte enhancer
      factor 2C interact to synergistically activate atrial natriuretic peptide and
      alpha-myosin heavy chain transcription. Furthermore, chromatin
      immunoprecipitation analysis in H9c2 cells treated with phenylephrine showed that
      dHAND and myocyte enhancer factor 2C protein complex bind to the A/T sequence on
      atrial natriuretic peptide promoter. Taken together, these results not only
      suggest that the complex cis-trans interaction of dHAND, myocyte enhancer factor
      2C, and the target gene may fine-tune gene expression in cardiac myocytes but
      also provide a molecular paradigm to elucidate the mechanisms of action of dHAND
      and myocyte enhancer factor 2C in the developing heart.

PMID- 15485824
TI  - Introduction of negative charge mimicking protein kinase C phosphorylation of
      cardiac troponin I. Effects on cardiac troponin C.
AB  - Protein kinase C phosphorylation of cardiac troponin, the Ca(2+)-sensing switch
      in muscle contraction, is capable of modulating the response of cardiac muscle to
      a Ca(2+) ion concentration. The N-domain of cardiac troponin I contains two
      protein kinase C phosphorylation sites. Although the physiological consequences
      of phosphorylation at Ser(43)/Ser(45) are known, the molecular mechanisms
      responsible for these functional changes have yet to be established. In this
      work, NMR was used to identify conformational and dynamic changes in cardiac
      troponin C upon binding a phosphomimetic troponin I, having Ser(43)/Ser(45)
      mutated to Asp. Chemical shift perturbation mapping indicated that residues in
      helix G were most affected. Smaller chemical shift changes were observed in
      residues located in the Ca(2+)/Mg(2+)-binding loops. Amide hydrogen/deuterium
      exchange rates in the C-lobe of troponin C were compared in complexes containing
      either the wild-type or phosphomimetic N-domain of troponin I. In the presence of
      a phosphomimetic domain, exchange rates in helix G increased, whereas a decrease
      in exchange rates for residues mapping to Ca(2+)/Mg(2+)-binding loops III and IV
      was observed. Increased exchange rates are consistent with destabilization of the
      Thr(129)-Asp(132) helix capping box previously characterized in helix G. The
      perturbation of helix G and metal binding loops III and IV suggests that
      phosphorylation alters metal ion affinity and inter-subunit interactions. Our
      studies support a novel mechanism for protein kinase C signal transduction,
      emphasizing the importance of C-lobe Ca(2+)/Mg(2+)-dependent troponin
      interactions.

PMID- 15485825
TI  - The notch ligand Delta1 recruits Dlg1 at cell-cell contacts and regulates cell
      migration.
AB  - Delta1 acts as a membrane-bound ligand that interacts with the Notch receptor and
      plays a critical role in cell fate specification. By using peptide affinity
      chromatography followed by mass spectrometry, we have identified Dlg1 as a
      partner of the Delta1 C-terminal region. Dlg1 is a human homolog of the
      Drosophila Discs large tumor suppressor, a member of the membrane-associated
      guanylate kinase family of molecular scaffolds. We confirmed this interaction by
      co-immunoprecipitation experiments between endogenous Dlg1 and transduced Delta1
      in a 3T3 cell line stably expressing Delta1. Moreover, we showed that deletion of
      a canonical C-terminal PDZ-binding motif (ATEV) in Delta1 abrogated this
      interaction. Delta4 also interacted with Dlg1, whereas Jagged1, another Notch
      ligand, did not. In HeLa cells, transfected Delta1 triggered the accumulation of
      endogenous Dlg1 at sites of cell-cell contact. Expression of Delta1 also reduced
      the motility of 3T3 cells. Finally, deletion of the ATEV motif totally abolished
      these effects but did not interfere with the ability of Delta1 to induce Notch
      signaling and T cell differentiation in co-culture experiments. These results
      point to a new, probably cell-autonomous function of Delta1, which is independent
      of its activity as a Notch ligand.

PMID- 15485826
TI  - The minimal essential unit for cadherin-mediated intercellular adhesion comprises
      extracellular domains 1 and 2.
AB  - N-cadherin comprises five homologous extracellular domains, a transmembrane, and
      a cytoplasmic domain. The extracellular domains of N-cadherin play important
      roles in homophilic cell adhesion, but the contribution of each domain to this
      phenomenon has not been fully evaluated. In particular, the following questions
      remain unanswered: what is the minimal domain combination that can generate cell
      adhesion, how is domain organization related to adhesive strength, and does the
      cytoplasmic domain serve to facilitate extracellular domain interaction? To
      address these issues, we made serial constructs of the extracellular domains of N
      cadherin and produced various cell lines to examine adhesion properties. We show
      that the first domain of N-cadherin alone on the cell surface fails to generate
      adhesive activity and that the first two domains of N-cadherin form the "minimal
      essential unit" to mediate cell adhesion. Cell lines expressing longer
      extracellular domains or N-cadherin wild type cells formed larger cellular
      aggregates than those expressing shorter aggregates. However, adhesion strength,
      as measured by a shearing test, did not reveal any differences among these
      aggregative cell lines, suggesting that the first two domains of N-cadherin cells
      generate the same strength of adhesive activity as longer extracellular domain
      cells. Furthermore, truncations of the first two domains of N-cadherin are also
      sufficient to form cisdimerization at an adhesive junction. Our findings suggest
      that the extracellular domains of N-cadherin have distinct roles in cell
      adhesion, i.e. the first two domains are responsible for homophilic adhesion
      activity, and the other domains promote adhesion efficiency most likely by
      positioning essential domains relatively far out from the cell surface.

PMID- 15485827
TI  - Modulation of the M2 muscarinic acetylcholine receptor activity with monoclonal
      anti-M2 receptor antibody fragments.
AB  - Antibodies directed against the second extracellular loop of G protein-coupled
      receptors are known to have functional activities. From a partial agonist
      monoclonal antibody directed against the M2 muscarinic receptor, we constructed
      and produced a single chain variable fragment with high affinity for its target
      epitope. The fragment is able to recognize its receptor on Chinese hamster ovary
      cells transfected with the M2 muscarinic acetylcholine receptor to block the
      effect of carbachol on this receptor and to exert an inverse agonist activity on
      the basal activity of the receptor. The antibody fragment is also able to
      increase the basal rhythm of cultured neonatal rat cardiomyocytes and to inhibit
      in a non-competitive manner the negative chronotropic effect of carbachol. This
      antibody fragment is able to exert its inverse agonist activity in vivo on mouse
      heart activity. The immunological strategy presented here could be useful to
      develop specific allosteric inverse agonist reagents for G protein-coupled
      receptors.

PMID- 15485828
TI  - Distinct roles for the alpha and beta subunits in the functions of integrin
      alphaMbeta2.
AB  - Integrin alphaMbeta2 (Mac-1, CD11b/CD18) is a noncovalently linked heterodimer of
      alphaM and beta2 subunits on the surface of leukocytes, where it plays a pivotal
      role in the adhesion and migration of these cells. Using HEK293 cells expressing
      alphaMbeta2 or the individual constituent chains on their surface, we analyzed
      the contributions of the alphaM or beta2 subunits to functional responses
      mediated by the integrin. In cells expressing only alphaM or beta2, the
      individual subunits were not associated with the endogenous integrins of the
      cells, and other partners for the subunits were not detected by surface labeling
      and immunoprecipitation under a variety of conditions. The alphaM cells mediated
      adhesion and spreading on a series of alphaMbeta2 ligands (fibrinogen, Factor X,
      iC3b, ICAM-1 (intercellular adhesion molecule-1), and denatured ovalbumin) but
      could not support cell migration to any of these. The spreading of the alphaM
      cells suggested an unanticipated linkage of this subunit to the cytoskeleton. The
      beta2 cells supported migration and attachment but not spreading on a subset of
      the alphaMbeta2 ligands. The heterodimeric receptor and its individual subunits
      were purified from the cells by affinity chromatography and recapitulated the
      ligand binding properties of the corresponding cell lines. These data indicate
      that each subunit of alphaMbeta2 contributes distinct properties to alphaMbeta2
      and that, in most but not all cases, the response of the integrin is a composite
      of the functions of its individual subunits.

PMID- 15485829
TI  - Conversion of mechanical force into biochemical signaling.
AB  - Physical forces play important roles in regulating cell proliferation,
      differentiation, and death by activating intracellular signal transduction
      pathways. How cells sense mechanical stimulation, however, is largely unknown.
      Most studies focus on cellular membrane proteins such as ion channels, integrins,
      and receptors for growth factors as mechanosensory units. Here we show that
      mechanical stretch-induced c-Src protein tyrosine kinase activation is mediated
      through the actin filament-associated protein (AFAP). Distributed along the actin
      filaments, AFAP can directly active c-Src through binding to its Src homology 3
      and/or 2 domains. Mutations at these specific binding sites on AFAP blocked
      mechanical stretch-induced c-Src activation. Therefore, mechanical force can be
      transmitted along the cytoskeleton, and interaction between cytoskeletal
      associated proteins and enzymes related to signal transduction may convert
      physical forces into biochemical reactions. Cytoskeleton deformation-induced
      protein-protein interaction via specific binding sites may represent a novel
      intracellular mechanism for cells to sense mechanical stimulation.

PMID- 15485830
TI  - Regulation of NF-kappa B2 p100 processing by its cis-acting domain.
AB  - Processing of NF-kappa B2 precursor protein p100 to generate p52 is tightly
      regulated. However, this proteolytic event could be actively induced by the NF
      kappa B-inducing kinase and the human T-cell leukemia virus-encoded oncoprotein
      Tax or be constitutively turned on due to the loss of the C-terminal portion of
      p100. Whereas NF-kappa B-inducing kinase-mediated p100 processing requires beta
      transducin repeat-containing protein, constitutive processing of p100 is
      independent of this protein. On the other hand, Tax-induced processing of p100
      appears to be both beta-transducin repeat-containing protein-dependent and 
      independent. We show here that, besides the C-terminal sequences, multiple
      functional regions, including the two alpha-helices, dimerization domain, nuclear
      localization sequence, and glycine-rich region, located in the N terminus of
      p100, also play important roles in both constitutive and inducible processing,
      suggesting a common mechanism for p100 processing. We further demonstrate that
      with the help of the C-terminal death domain and I kappa B kinase alpha-targeting
      serines, the C-terminal ankyrin-repeat domain of p100 strongly interacts with its
      N-terminal dimerization domain and nuclear localization sequence, thereby
      bringing the C- and N-terminal sequences together to form a three-dimensional
      domain. This presumptive domain is not only responsible for suppression of
      constitutive processing but also required for inducible processing of p100. Taken
      together, these studies highlight the mechanism by which the different sequences
      within p100 work in concert to regulate its processing and shed light on the
      mechanisms of how p100 processing is tightly and delicately controlled.

PMID- 15485831
TI  - Osteoclast differentiation is impaired in the absence of inhibitor of kappa B
      kinase alpha.
AB  - Signaling through the receptor activator of nuclear factor kappa B (RANK) is
      required for both osteoclast differentiation and mammary gland development, yet
      the extent to which RANK utilizes similar signaling pathways in these tissues
      remains unclear. Mice expressing a kinase-inactive form of the inhibitor of kappa
      B kinase alpha (IKK alpha) have mammary gland defects similar to those of RANK
      null mice yet have apparently normal osteoclast function. Because mice that
      completely lack IKK alpha have severe skin and skeletal defects that are not
      associated with IKK alpha-kinase activity, we wished to directly examine
      osteoclastogenesis in IKK alpha(-/-) mice. We found that unlike RANK-null mice,
      which completely lack osteoclasts, IKK alpha(-/-) mice did possess normal numbers
      of TRAP(+) osteoclasts. However, only 32% of these cells were multinucleated
      compared with 57% in wild-type littermates. A more profound defect in
      osteoclastogenesis was observed in vitro using IKK alpha(-/-) hematopoietic cells
      treated with colony-stimulating factor 1 and RANK ligand (RANKL), as the cells
      failed to form large, multinucleated osteoclasts. Additionally, overall RANKL
      induced global gene expression was significantly blunted in IKK alpha(-/-) cells,
      including osteoclast-specific genes such as TRAP, MMP-9, and c-Src. IKK alpha was
      not required for RANKL-mediated I kappa B alpha degradation or phosphorylation of
      mitogen-activated protein kinases but was required for RANKL-induced p100
      processing. Treatment of IKK alpha(-/-) cells with tumor necrosis factor alpha
      (TNF alpha) in combination with RANKL led to partial rescue of osteoclastogenesis
      despite a lack of p100 processing. However, the ability of TNF alpha alone or in
      combination with transforming growth factor beta to induce osteoclast
      differentiation was dependent on IKK alpha, suggesting that synergy between RANKL
      and TNFalpha can overcome p100 processing defects in IKK alpha(-/-) cells.

PMID- 15485832
TI  - The junctional adhesion molecule-C promotes neutrophil transendothelial migration
      in vitro and in vivo.
AB  - The third member of the family of junctional adhesion molecules (JAMs), JAM-3,
      also called JAM-C, was recently shown to be a novel counter-receptor on platelets
      for the leukocyte beta(2)-integrin Mac-1 (alphaMbeta(2), CD11b/CD18). Here, new
      functional aspects of the role of endothelial cell JAM-C were investigated.
      Endothelial cells express JAM-C, which is predominantly localized within
      junctions at interendothelial contacts, since it codistributes with a tight
      junction component, zonula occludens-1. Whereas JAM-C does not participate in
      neutrophil adhesion to endothelial cells, it mediates neutrophil transmigration
      in a Mac-1-dependent manner. In particular, inhibition of JAM-C significantly
      reduced neutrophil transendothelial migration, and the combination of JAM-C and
      platelet/endothelial cell adhesion molecule-1 blockade almost completely
      abolished neutrophil transendothelial migration in vitro. In vivo, inhibition of
      JAM-C with soluble mouse JAM-C resulted in a 50% reduction of neutrophil
      emigration in the mouse model of acute thioglycollate-induced peritonitis. Thus,
      JAM-C participates in neutrophil transmigration and thereby provides a novel
      molecular target for antagonizing interactions between vascular cells that
      promote inflammatory vascular pathologies.

PMID- 15485833
TI  - ARPC1/Arc40 mediates the interaction of the actin-related protein 2 and 3 complex
      with Wiskott-Aldrich syndrome protein family activators.
AB  - The actin-related protein 2 and 3 (Arp2/3) complex is a seven-subunit protein
      complex that nucleates actin filaments at the cell cortex. Despite extensive
      cross-linking, crystallography, genetic and biochemical studies, the contribution
      of each subunit to the activity of the complex remains largely unclear. In this
      study we characterized the function of the 40-kDa subunit, ARPC1/Arc40, of the
      yeast Arp2/3 complex. We showed that this subunit is indeed a stable component of
      the Arp2/3 complex, but its highly unusual electrophoretic mobility eluded
      detection in previous studies. Recombinant Arc40 bound the VCA domain of Wiskott
      Aldrich syndrome protein family activators at a K(d) of 0.45 mum, close to that
      of the full complex with VCA (0.30 microm), and this interaction was dependent on
      the conserved tryptophan at the COOH terminus of VCA. Using a newly constructed
      Delta arc40 yeast strain, we showed that loss of Arc40 severely reduced the
      binding affinity of the Arp2/3 complex with VCA as well as the nucleation
      activity of the complex, suggesting that Arc40 contains an important contact site
      of the Arp2/3 complex with VCA. The Delta arc40 cells exhibited reduced growth
      rate, loss of actin patches, and accumulation of cables like actin aggregates,
      phenotypes typical of other subunit nulls, suggesting that Arc40 functions
      exclusively within the Arp2/3 complex.

PMID- 15485834
TI  - Kinetic mechanism and metabolic role of pyruvate phosphate dikinase from
      Entamoeba histolytica.
AB  - The kinetic mechanism and the metabolic role of pyruvate phosphate dikinase from
      Entamoeba histolytica were investigated. The initial velocity patterns in double
      reciprocal plots were parallel for the phosphoenolpyruvate/AMP and
      phosphoenolpyruvate/pyrophosphate substrate pairs and intersecting for the
      AMP/pyrophosphate pair. This suggests a kinetic mechanism with two independent
      reactions. The rate of ATP synthesis at saturating and equimolar concentrations
      of phosphoenolpyruvate, AMP, and pyrophosphate was inhibited by phosphate, which
      is consistent with an ordered steady-state mechanism. Enzyme phosphorylation by
      [(32)P(i)]pyrophosphate depends on the formation of a ternary complex between
      AMP, pyrophosphate, and pyruvate phosphate dikinase. In consequence, the reaction
      that involves the AMP/pyrophosphate pair follows a sequential steady-state
      mechanism. The product inhibition patterns of ATP and phosphate versus
      phosphoenolpyruvate were noncompetitive and uncompetitive, respectively,
      suggesting that these products were released in an ordered process (phosphate
      before ATP). The ordered release of phosphate and ATP and the noncompetitive
      inhibition patterns of pyruvate versus AMP and versus pyrophosphate also
      supported the sequential kinetic mechanism between AMP and pyrophosphate. Taken
      together, our data provide evidence for a uni uni bi bi pingpong mechanism for
      recombinant pyruvate phosphate dikinase from E. histolytica. The Delta G value
      for the reaction catalyzed by pyruvate phosphate dikinase (+2.7 kcal/mol)
      determined under near physiological conditions indicates that the synthesis of
      ATP is not thermodynamically favorable in trophozoites of E. histolytica.

PMID- 15485836
TI  - A fully recombinant system for activator-dependent archaeal transcription.
AB  - The core components of the archaeal transcription apparatus closely resemble
      those of eukaryotic RNA polymerase II, while the DNA-binding transcriptional
      regulators are predominantly of bacterial type. Here we report the construction
      of an entirely recombinant system for positively regulated archaeal
      transcription. By omitting individual subunits, or sets of subunits, from the in
      vitro assembly of the 12-subunit RNA polymerase from the hyperthermophile
      Methanocaldococcus jannaschii, we describe a functional dissection of this RNA
      polymerase II-like enzyme, and its interactions with the general transcription
      factor TFE, as well as with the transcriptional activator Ptr2.

PMID- 15485835
TI  - Fas-associated protein with death domain (FADD)-independent recruitment of c
      FLIPL to death receptor 5.
AB  - Here we show a novel mechanism by which FLICE-like inhibitory protein (c-FLIP)
      regulates apoptosis induced by tumor necrosis factor (TNF)-related apoptosis
      inducing ligand (TRAIL) and one of its receptors, DR5. c-FLIP is a critical
      regulator of the TNF family of cytokine receptor signaling. c-FLIP has been
      postulated to prevent formation of the competent death-inducing signaling complex
      (DISC) in a ligand-dependent manner, through its interaction with FADD and/or
      caspase-8. In order to identify regulators of TRAIL function, we used the
      intracellular death domain (DD) of DR5 as a target to screen a phage-displayed
      combinatorial peptide library. The DD of DR5 selected from the library a peptide
      that showed sequence similarity to a stretch of amino acids in the C terminus of
      c-FLIP(L). The phage-displayed peptide selectively interacted with the DD of DR5
      in in vitro binding assays. Similarly, full-length c-FLIP (c-FLIP(L)) and the C
      terminal p12 domain of c-FLIP interacted with DR5 both in in vitro pull-down
      assays and in mammalian cells. This interaction was independent of TRAIL. To the
      contrary, TRAIL treatment released c-FLIP(L) from DR5, permitting the recruitment
      of FADD to the active DR5 signaling complex. By employing FADD-deficient Jurkat
      cells, we demonstrate that DR5 and c-FLIP(L) interact in a FADD-independent
      manner. Moreover, we show that a cellular membrane permeable version of the
      peptide corresponding to the DR5 binding domain of c-FLIP induces apoptosis in
      mammalian cells. Taken together, these findings indicate that c-FLIP interacts
      with the DD of DR5, thus preventing death (L)signaling by DR5 prior to the
      formation of an active DISC. Because TRAIL and DR5 are ubiquitously expressed,
      the interaction of c-FLIP(L) and DR5 indicates a mechanism by which tumor
      selective apoptosis can be achieved through protecting normal cells from
      undergoing death receptor-induced apoptosis.

PMID- 15485837
TI  - NAK is recruited to the TNFR1 complex in a TNFalpha-dependent manner and mediates
      the production of RANTES: identification of endogenous TNFR-interacting proteins
      by a proteomic approach.
AB  - Tumor necrosis factor alpha (TNFalpha) is a proinflammatory cytokine with
      pleiotropic immunological and biological activities. TNFalpha signaling is
      triggered by the engagement of soluble TNFalpha to two types of cell surface
      receptors, TNFR1 and TNFR2. This recruits cytosolic proteins to the intracellular
      domains of the receptors and initiates signaling to downstream effectors. In this
      study, we used a proteomic approach to identify these cytosolic proteins from
      affinity-purified, endogenous TNFalpha.TNFR complexes in human myelomonocytic
      U937 cells. Seven proteins were identified, including TRADD, TRAP2, and TRAF2,
      which are three proteins known to be recruited to TNFalpha receptors. NAK,
      RasGAP3, TRCP1, and TRCP2 were also identified. We further showed that NAK is
      recruited to TNFR1 in a temporally regulated and TNFalpha-dependent manner and
      that it mediates the TNFalpha-induced production of the chemokine RANTES
      (regulated on activation normal T cell expressed and secreted). These data
      demonstrate that NAK is a component of the TNFalpha.TNFR1 signaling complex and
      confirm the physiological role of NAK in the TNFalpha-mediated response.

PMID- 15485838
TI  - Stimulation of toll-like receptor 2 by Coxiella burnetii is required for
      macrophage production of pro-inflammatory cytokines and resistance to infection.
AB  - Innate and adaptive immune responses are initiated upon recognition of microbial
      molecules by Toll-like receptors (TLRs). We have investigated the importance of
      these receptors in the induction of pro-inflammatory cytokines and macrophage
      resistance to infection with Coxiella burnetii, an obligate intracellular
      bacterium and the etiological agent of Q fever. By using a Chinese hamster
      ovary/CD14 cell line expressing either functional TLR2 or TLR4, we determined
      that C. burnetii phase II activates TLR2 but not TLR4. Macrophages deficient for
      TLR2, but not TLR4, produced less tumor necrosis factor-alpha and interleukin-12
      upon C. burnetii infection. Furthermore, it was found that TLR2 activation
      interfered with C. burnetii intracellular replication, as macrophages from TLR2
      deficient mice were highly permissive for C. burnetii growth compared with
      macrophages from wild type mice or TLR4-deficient mice. Although LPS
      modifications distinguish virulent C. burnetii phase I bacteria from avirulent
      phase II organisms, electrospray ionization-mass spectrometry analysis showed
      that the lipid A moieties isolated from these two phase variants are identical.
      Purified lipid A derived from either phase I or phase II LPS failed to activate
      TLR2 and TLR4. Indeed, the lipid A molecules were able to interfere with TLR4
      signaling in response to purified Escherichia coli LPS. These studies indicate
      that TLR2 is an important host determinant that mediates recognition of C.
      burnetii and a response that limits growth of this intracellular pathogen.

PMID- 15485839
TI  - Regulation of the HscA ATPase reaction cycle by the co-chaperone HscB and the
      iron-sulfur cluster assembly protein IscU.
AB  - The ATPase activity of HscA, a specialized hsp70 molecular chaperone from
      Escherichia coli, is regulated by the iron-sulfur cluster assembly protein IscU
      and the J-type co-chaperone HscB. IscU behaves as a substrate for HscA, and HscB
      enhances the binding of IscU to HscA. To better understand the mechanism by which
      HscB and IscU regulate HscA, we examined binding of HscB to the different
      conformational states of HscA and the effects of HscB and IscU on the kinetics of
      the individual steps of the HscA ATPase reaction cycle. Affinity sensor studies
      revealed that whereas IscU binds both ADP (R-state) and ATP (T-state) HscA
      complexes, HscB interacts only with an ATP-bound state. Studies of ATPase
      activity under single-turnover and rapid mixing conditions showed that both IscU
      and HscB interact with the low peptide affinity T-state of HscA (HscA++.ATP) and
      that both modestly accelerate (3-10-fold) the rate-determining steps in the HscA
      reaction cycle, k(hyd) and k(T-->R). When present together, IscU and HscB
      synergistically stimulate both k(hyd) (approximately = 500-fold) and k(T-->R)
      (approximately = 60-fold), leading to enhanced formation of the HscA.ADP-IscU
      complex (substrate capture). Following ADP/ATP exchange, IscU also stimulates k(R
      ->T) (approximately = 50-fold) and thereby accelerates the rate at which the low
      peptide affinity HscA++.ATP T-state is regenerated. Because HscA nucleotide
      exchange is fast, the overall rate of the chaperone cycle in vivo will be
      determined by the availability of the IscU-HscB substrate-co-chaperone complex.

PMID- 15485840
TI  - Defective mitochondrial protein translocation precludes normal Caenorhabditis
      elegans development.
AB  - We demonstrate biochemically that the genes identified by sequence similarity as
      orthologs of the mitochondrial import machinery are functionally conserved in
      Caenorhabditis elegans. Specifically, tin-9.1 and tin-10 RNA interference (RNAi)
      treatment of nematodes impairs import of the ADP/ATP carrier into isolated
      mitochondria. Developmental phenotypes are associated with gene knock-down of the
      mitochondrial import components. RNAi of tomm-7 and ddp-1 resulted in
      mitochondria with an interconnected morphology in vivo, presumably due to defects
      in the assembly of outer membrane fission/fusion components. RNAi of the small
      Tim proteins TIN-9.1, TIN-9.2, and TIN-10 resulted in a small body size, reduced
      number of progeny produced, and partial embryonic lethality. An additional
      phenotype of the tin-9.2(RNAi) animals is defective formation of the somatic
      gonad. The biochemical demonstration that the protein import activity is reduced,
      under the same conditions that yield the defects in specific tissues and
      lethality in a later generation, suggests that the developmental abnormalities
      observed are a consequence of defects in mitochondrial inner membrane biogenesis.

PMID- 15485841
TI  - Vav2 as a Rac-GDP/GTP exchange factor responsible for the nectin-induced, c-Src-
      and Cdc42-mediated activation of Rac.
AB  - Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules
      that form homo- and hetero-trans-dimers (trans-interactions). Nectins first form
      cell-cell contact and then recruit cadherins to the nectin-based cell-cell
      contact sites to form adherens junctions cooperatively with cadherins. In
      addition, the trans-interactions of nectins induce the activation of Cdc42 and
      Rac small G proteins, which enhances the formation of adherens junctions by
      forming filopodia and lamellipodia, respectively. The trans-interactions of
      nectins first recruit and activate c-Src at the nectin-based cell-cell contact
      sites. c-Src then phosphorylates and activates FRG, a Cdc42-GDP/GTP exchange
      factor (GEF) for Cdc42. The activation of both c-Src and Cdc42 by FRG is
      necessary for the activation of Rac, but the Rac-GEF responsible for this
      activation of Rac remains unknown. We showed here that the nectin-induced
      activation of Rac was inhibited by a dominant negative mutant of Vav2, a Rac-GEF.
      Nectins recruited and tyrosine-phosphorylated Vav2 through c-Src at the nectin
      based cell-cell contact sites, whereas Cdc42 was not necessary for the nectin
      induced recruitment of Vav2 or the nectin-induced, c-Src-mediated tyrosine
      phosphorylation of Vav2. Cdc42 activated through c-Src then enhanced the GEF
      activity of tyrosine-phosphorylated Vav2 on Rac1. These results indicate that
      Vav2 is a GEF responsible for the nectin-induced, c-Src-, and Cdc42-mediated
      activation of Rac.

PMID- 15485842
TI  - The function of mitogen-activated protein kinase phosphatase-1 in peptidoglycan
      stimulated macrophages.
AB  - Mitogen-activated protein (MAP) kinases play a pivotal role in the macrophages in
      the production of proinflammatory cytokines triggered by lipopolysaccharides.
      However, their function in the responses of macrophages to Gram-positive bacteria
      is poorly understood. Even less is known about the attenuation of MAP kinase
      signaling in macrophages exposed to Gram-positive bacteria. In the present study,
      we have investigated the regulation of MAP kinases and the role of MAP kinase
      phosphatase (MKP)-1 in the production of pro-inflammatory cytokines using murine
      RAW264.7 and primary peritoneal macrophages after peptidoglycan stimulation.
      Treatment of macrophages with peptidoglycan resulted in a transient activation of
      JNK, p38, and extracellular signal-regulated kinase. Most interestingly, MKP-1
      expression was potently induced by peptidoglycan, and this induction was
      concurrent with MAP kinase dephosphorylation. Triptolide, a diterpenoid
      triepoxide, potently blocked the induction of MKP-1 by peptidoglycan and
      prolonged the activation of JNK and p38. Overexpression of MKP-1 substantially
      attenuated the production of tumor necrosis factor (TNF)-alpha induced by
      peptidoglycan, whereas knockdown of MKP-1 by small interfering RNA substantially
      increased the production of both TNF-alpha and interleukin-1 beta. Finally, we
      found that in primary murine peritoneal macrophages, MKP-1 induction following
      peptidoglycan stimulation also coincided with inactivation of JNK and p38.
      Blockade of MKP-1 induction resulted in a sustained activation of both JNK and
      p38 in primary macrophages. Our results reveal that MKP-1 critically regulates
      the expression of TNF-alpha and interleukin-1 beta in RAW264.7 cells and further
      suggest a central role for this phosphatase in controlling the inflammatory
      responses of primary macrophages to Gram-positive bacterial infection.

PMID- 15485843
TI  - NF-kappaB family proteins participate in multiple steps of hematopoiesis through
      elimination of reactive oxygen species.
AB  - To examine the roles for NF-kappaB family proteins in hematopoiesis, we first
      expressed dominant negative Rel/NF-kappaB(IkappaBSR) in a factor-dependent cell
      line, Ba/F3. Although IkappaBSR neither affected thrombopoietin-dependent nor
      gp130-mediated growth, it suppressed interleukin-3- and erythropoietin-dependent
      growth at low concentrations. In addition, IkappaBSR enhanced factor-deprived
      apoptosis through the accumulation of reactive oxygen species (ROS). When
      expressed in normal hematopoietic stem/progenitor cells, IkappaBSR induced
      apoptosis even in the presence of appropriate cytokines by accumulating ROS. We
      also expressed IkappaBSR in an inducible fashion at various stages of
      hematopoiesis using the OP9 system, in which hematopoietic cells are induced to
      develop from embryonic stem cells. When IkappaBSR was expressed at the stage of
      Flk-1(+) cells (putative hemangioblasts), IkappaBSR inhibited the development of
      primitive hematopoietic progenitor cells by inducing apoptosis through the ROS
      accumulation. Furthermore, when IkappaBSR was expressed after the development of
      hematopoietic progenitor cells, it inhibited their terminal differentiation
      toward erythrocytes, megakaryocytes, and granulocytes by inducing apoptosis
      through the ROS accumulation. These results indicate that NF-kappaB is required
      for preventing apoptosis at multiple steps of hematopoiesis by eliminating ROS.

PMID- 15485844
TI  - Characterization of the ligand binding site of the bovine IgA Fc receptor (bFc
      alpha R).
AB  - Recently, we identified a bovine IgA Fc receptor (bFc alpha R), which shows high
      homology to the human myeloid Fc alpha R, CD89. IgA binding has previously been
      shown to depend on several specific residues located in the B-C and F-G loops of
      the membrane-distal extracellular domain 1 of CD89. To compare the ligand binding
      properties of these two Fc alpha Rs, we have mapped the IgA binding site of bFc
      alpha R. We show that, in common with CD89, Tyr-35 in the B-C loop is essential
      for IgA binding. However, in contrast to earlier observations on CD89, mutation
      of residues in the F-G loop did not significantly inhibit IgA binding.

PMID- 15485845
TI  - Evidence for glucocorticoid receptor transport on microtubules by dynein.
AB  - Rapid, ligand-dependent movement of glucocorticoid receptors (GR) from cytoplasm
      to the nucleus is hsp90-dependent, and much of the movement system has been
      defined. GR.hsp90 heterocomplexes isolated from cells contain one of several
      hsp90-binding immunophilins that link the complex to cytoplasmic dynein, a
      molecular motor that processes along microtubular tracks to the nucleus. The
      immunophilins link to dynein indirectly via the dynamitin component of the dynein
      associated dynactin complex (Galigniana, M. D., Harrell, J. M., O'Hagen, H. M.,
      Ljungman, M., and Pratt, W. B. (2004) J. Biol. Chem. 279, 22483-22489). Although
      it is known that rapid, hsp90-dependent GR movement requires intact microtubules,
      it has not been shown that the movement is dynein-dependent. Here, we show that
      overexpression of dynamitin, which blocks movement by dissociating the dynein
      motor from its cargo, inhibits ligand-dependent movement of the GR to the
      nucleus. We show that native GR.hsp90.immnunophilin complexes contain dynamitin
      as well as dynein and that GR heterocomplexes isolated from cytosol containing
      paclitaxel and GTP to stabilize microtubules also contain tubulin. The complete
      movement system, including the dynein motor complex and tubulin, can be assembled
      under cell-free conditions by incubating GR immune pellets with paclitaxel/GTP
      stabilized cytosol prepared from GR(-) L cells. This is the first evidence that
      the movement of a steroid receptor is dynein-dependent, and it is the first
      isolation of a steroid receptor bound to the entire system that determines its
      retrograde movement.

PMID- 15485846
TI  - Palmitoylation of inducible nitric-oxide synthase at Cys-3 is required for proper
      intracellular traffic and nitric oxide synthesis.
AB  - A number of cell types express inducible nitric-oxide synthase (NOS2) in response
      to exogenous insults such as bacterial lipopolysaccharide or proinflammatory
      cytokines. Although it has been known for some time that the N-terminal end of
      NOS2 suffers a post-translational modification, its exact identification has
      remained elusive. Using radioactive fatty acids, we show herein that NOS2 becomes
      thioacylated at Cys-3 with palmitic acid. Site-directed mutagenesis of this
      single residue results in the absence of the radiolabel incorporation. Acylation
      of NOS2 is completely indispensable for intracellular sorting and .NO synthesis.
      In fact, a C3S mutant of NOS2 is completely inactive and accumulates to
      intracellular membranes that almost totally co-localize with the Golgi marker
      beta-cop. Likewise, low concentrations of the palmitoylation blocking agents 2-Br
      palmitate or 8-Br-palmitate severely affected the .NO synthesis of both NOS2
      induced in muscular myotubes and transfected NOS2. However, unlike endothelial
      NOS, palmitoylation of inducible NOS is not involved in its targeting to
      caveolae. We have created 16 NOS2-GFP chimeras to inspect the effect of the
      neighboring residues of Cys-3 on the degree of palmitoylation. In this regard,
      the hydrophobic residue Pro-4 and the basic residue Lys-6 seem to be
      indispensable for palmitoylation. In addition, agents that block the endoplasmic
      reticulum to Golgi transit such as brefeldin A and monensin drastically reduced
      NOS2 activity leading to its accumulation in perinuclear areas. In summary,
      palmitoylation of NOS2 at Cys-3 is required for both its activity and proper
      intracellular localization.

PMID- 15485847
TI  - Endothelial cell confluence regulates cyclooxygenase-2 and prostaglandin E2
      production that modulate motility.
AB  - Endothelial cells line the vasculature and, after mechanical denudation during
      invasive procedures or cellular loss from natural causes, migrate to reestablish
      a confluent monolayer. We find confluent monolayers of human umbilical vein
      endothelial cells were quiescent and expressed low levels of cyclooxygenase-2,
      but expressed cyclooxygenase-2 at levels comparable with cytokine-stimulated
      cells when present in a subconfluent culture. Mechanically wounding endothelial
      cell monolayers stimulated rapid cyclooxygenase-2 expression that increased with
      the level of wounding. Cyclooxygenase-2 re-expression occurred throughout the
      culture, suggesting signaling from cells proximal to the wound to distal cells.
      Media from wounded monolayers stimulated cyclooxygenase-2 expression in confluent
      monolayers, which correlated with the level of wounding of the donor monolayer.
      Wounded monolayers and cells in subconfluent cultures secreted enhanced levels of
      prostaglandin (PG) E(2) that depended on cyclooxygenase-2 activity, and PGE(2)
      stimulated cyclooxygenase-2 expression in confluent endothelial cell monolayers.
      Cells from subconfluent monolayers migrated through filters more readily than
      those from confluent monolayers, and the cyclooxygenase-2-selective inhibitor NS
      398 suppressed migration. Adding PGE(2) to NS-398-treated cells augmented
      migration. Endothelial cells also migrated into mechanically denuded areas of
      confluent monolayers, and this too was suppressed by NS-398. We conclude that
      endothelial cells not in contact with neighboring cells express cyclooxygenase-2
      that results in enhanced release of PGE(2), and that this autocrine and paracrine
      loop enhances endothelial cell migration to cover denuded areas of the
      endothelium.

PMID- 15485848
TI  - Site-specific phosphorylation of phosducin in intact retina. Dynamics of
      phosphorylation and effects on G protein beta gamma dimer binding.
AB  - Phosducin (Pdc) is a G protein beta gamma dimer (G beta gamma) binding protein,
      highly expressed in retinal photoreceptor and pineal cells, yet whose
      physiological role remains elusive. Light controls the phosphorylation of Pdc in
      a cAMP and Ca(2+)-dependent manner, and phosphorylation in turn regulates the
      binding of Pdc to G(t)beta gamma or 14-3-3 proteins in vitro. To directly examine
      the phosphorylation of Pdc in intact retina, we prepared antibodies specific to
      the three principal phosphorylation sites (Ser-54, Ser-73, and Ser-106) and
      measured the kinetics of phosphorylation/dephosphorylation during light/dark
      adaptation and the subsequent effects on G(t)beta gamma binding. Ser-54
      phosphorylation increased slowly (t((1/2)) approximately 90 min) during dark
      adaptation to approximately 70% phosphorylated and decreased rapidly (t((1/2))
      approximately 2 min) during light adaptation to less than 20% phosphorylated. Ser
      73 phosphorylation increased much faster during dark adaptation (t((1/2))
      approximately 3 min) to approximately 50% phosphorylated and decreased more
      slowly during light adaptation (t((1/2)) approximately 9 min) to less than 20%
      phosphorylated. The Ca(2+) chelator BAPTA-AM blocked Ser-54 phosphorylation
      during dark adaptation but had no effect on Ser-73 phosphorylation. In contrast,
      Ser-106 was not phosphorylated in either the light or dark. Importantly, G beta
      gamma binding to Pdc was enhanced by Ca(2+) chelation and the binding kinetics
      closely paralleled those of Ser-54 dephosphorylation, indicating that Ser-54
      phosphorylation controls G(t)beta gamma binding in vivo. These results suggest a
      pivotal role of Ser-54 and Ser-73 phosphorylation in determining the interactions
      of Pdc with its binding partners, G(t)beta gamma and 14-3-3 protein, which may
      regulate the light-dependent translocation of the photoreceptor G protein.

PMID- 15485850
TI  - Identification of a new presenilin-dependent zeta-cleavage site within the
      transmembrane domain of amyloid precursor protein.
AB  - Gamma-secretase cleavage of beta-amyloid precursor protein (APP) is crucial in
      the pathogenesis of Alzheimer disease, because it is the decisive step in the
      formation of the C terminus of beta-amyloid protein (Abeta). To better understand
      the molecular events involved in gamma-secretase cleavage of APP, in this study
      we report the identification of a new intracellular long Abeta species containing
      residues 1-46 (Abeta46), which led to the identification of a novel zeta-cleavage
      site between the known gamma- and epsilon-cleavage sites within the transmembrane
      domain of APP. Our data clearly demonstrate that the new zeta-cleavage is a
      presenilin-dependent event. It is also noted that the new zeta-cleavage site at
      Abeta46 is the APP717 mutation site. Furthermore, we show that the new zeta
      cleavage is inhibited by gamma-secretase inhibitors known as transition state
      analogs but less affected by inhibitors known as non-transition state gamma
      secretase inhibitors. Thus, the identification of Abeta46 establishes a system to
      determine the specificity or the preference of the known gamma-secretase
      inhibitors by examining their effects on the formation or turnover of Abeta46.

PMID- 15485849
TI  - The TRK1 potassium transporter is the critical effector for killing of Candida
      albicans by the cationic protein, Histatin 5.
AB  - The principal feature of killing of Candida albicans and other pathogenic fungi
      by the catonic protein Histatin 5 (Hst 5) is loss of cytoplasmic small molecules
      and ions, including ATP and K(+), which can be blocked by the anion channel
      inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. We constructed C.
      albicans strains expressing one, two, or three copies of the TRK1 gene in order
      to investigate possible roles of Trk1p (the organism's principal K(+)
      transporter) in the actions of Hst 5. All measured parameters (Hst 5 killing, Hst
      5-stimulated ATP efflux, normal Trk1p-mediated K(+) ((86)Rb(+)) influx, and Trk1p
      mediated chloride conductance) were similarly reduced (5-7-fold) by removal of a
      single copy of the TRK1 gene from this diploid organism and were fully restored
      by complementation of the missing allele. A TRK1 overexpression strain of C.
      albicans, constructed by integrating an additional TRK1 gene into wild-type
      cells, demonstrated cytoplasmic sequestration of Trk1 protein, along with
      somewhat diminished toxicity of Hst 5. These results could be produced either by
      depletion of intracellular free Hst 5 due to sequestered binding, or to
      cooperativity in Hst 5-protein interactions at the plasma membrane. Furthermore,
      Trk1p-mediated chloride conductance was blocked by 4,4'-diisothiocyanatostilbene
      2,2'-disulfonic acid in all of the tested strains, strongly suggesting that the
      TRK1 protein provides the essential pathway for ATP loss and is the critical
      effector for Hst 5 toxicity in C. albicans.

PMID- 15485851
TI  - T cell antigen receptor peptide-lipid membrane interactions using surface plasmon
      resonance.
AB  - This study examines the binding properties of a new class of immunomodulating
      peptides derived from the transmembrane region of the T cell antigen receptor, on
      model membranes using surface plasmon resonance. The di-basic "core" peptide was
      found to bind to both zwitterionic and anionic model membranes as well as to a T
      cell membrane preparation. By contrast, switching one or both of the basic
      residues to acidic residues led to a complete loss of binding to model membranes.
      In addition, the position of the charged amino acids in the sequence, the number
      of hydrophobic amino acids between the charged residues, and substitution of one
      or both basic to neutral amino acids were found to effect binding. These results
      when compared with in vitro T cell stimulation assays and in vivo adjuvant
      induced arthritis models, showed very close correlation and confirmed the
      findings that amino acid charge and location may have a role in peptide activity.
      These initial biophysical peptide-membrane interactions are critically important
      and correlate well with the subsequent cellular expression and biological effect
      of these hydrophobic peptides. Targeting and understanding the biophysical
      interactions between peptides and membranes at their site of action is paramount
      to the description of cell function and drug design.

PMID- 15485852
TI  - Streptococcus pneumoniae-induced p38 MAPK-dependent phosphorylation of RelA at
      the interleukin-8 promotor.
AB  - Streptococcus pneumoniae is the major cause of community-acquired pneumonia and
      one of the most common causes of death by infectious disease in industrialized
      countries. Little is known concerning the mechanisms of target cell activation in
      this disease. The present study shows that NF-kappaB and p38 MAPK signaling
      pathways contribute to chemokine synthesis by lung epithelial cells in response
      to pneumococci. In infected lungs of mice pneumococci stimulate expression of the
      interleukin (IL)-8 homolog keratinocyte-derived chemokine and granulocyte
      macrophage colony-stimulating factor, as well as activate p38 MAPK. Human
      bronchial epithelium was chosen as a cellular model, because it establishes the
      first barrier against pathogens, and little is known about its function in innate
      immunity. Pneumococci infection induces expression of IL-8 and granulocyte
      macrophage colony-stimulating factor as well as activation of p38 MAPK in human
      bronchial epithelial cells (BEAS-2B). Inhibition of p38 MAPK activity by SB202190
      and SB203580 blocks pneumococci-induced cytokine release. In mouse lungs in vivo
      as well as in cultured cells, pneumococci activate NF-kappaBinanIkappaB kinase
      dependent manner. Inhibition of p38 MAPK by chemical inhibitors or by RNA
      interference targeting p38alpha reduces pneumococci-induced NF-kappaB-dependent
      gene transcription. Blockade of p38 activity did not affect inducible nuclear
      translocation and recruitment of NF-kappaB/RelA to the IL-8 promotor but did
      reduce the level of phosphorylated RelA (serine 536) at IL-8 promotor and
      inhibited pneumococci-mediated recruitment of RNA polymerase II to IL-8 promotor.
      Thus, p38 MAPK contributes to pneumococci-induced chemokine transcription by
      modulating p65 NF-kappaB-mediated transactivation.

PMID- 15485853
TI  - Atypical soluble guanylyl cyclases in Drosophila can function as molecular oxygen
      sensors.
AB  - Conventional soluble guanylyl cyclases are heterodimeric enzymes that synthesize
      cGMP and are activated by nitric oxide. Recently, a separate class of soluble
      guanylyl cyclases has been identified that are only slightly activated by or are
      insensitive to nitric oxide. These atypical guanylyl cyclases include the
      vertebrate beta2 subunit and examples from the invertebrates Manduca sexta,
      Caenorhabditis elegans, and Drosophila melanogaster. A member of this family, GCY
      35 in C. elegans, was recently shown to be required for a behavioral response to
      low oxygen levels and may be directly regulated by oxygen (Gray, J. M., Karow, D.
      S., Lu, H., Chang, A. J., Chang, J. S., Ellis, R. E., Marletta, M. A., and
      Bargmann, C. I. (2004) Nature 430, 317-322). Drosophila contains three genes that
      code for atypical soluble guanylyl cyclases: Gyc-88E, Gyc-89Da, and Gyc-89Db. COS
      7 cells co-transfected with Gyc-88E and Gyc-89Da or Gyc-89Db accumulate low
      levels of cGMP under normal atmospheric oxygen concentrations and are potently
      activated under anoxic conditions. The increase in activity is graded over oxygen
      concentrations of 0-21%, can be detected within 1 min of exposure to anoxic
      conditions and is blocked by the soluble guanylyl cyclase inhibitor, 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ). Gyc-88E and Gyc-89Db are co
      expressed in a subset of sensory neurons where they would be ideally situated to
      act as oxygen sensors. This is the first demonstration of a soluble guanylyl
      cyclase that is activated in response to changing oxygen concentrations.

PMID- 15485854
TI  - The topology of the Lcb1p subunit of yeast serine palmitoyltransferase.
AB  - The structural organization and topology of the Lcb1p subunit of yeast and
      mammalian serine palmitoyltransferases (SPT) were investigated. In the yeast
      protein, three membrane-spanning domains were identified by insertion of
      glycosylation and factor Xa cleavage sites at various positions. The first domain
      of the yeast protein, located between residues 50 and 84, was not required for
      the stability, membrane association, interaction with Lcb2p, or enzymatic
      activity. Deletion of the comparable domain of the mammalian protein SPTLC1 also
      had little effect on its function, demonstrating that this region is not required
      for membrane localization or heterodimerization with SPTLC2. The second and third
      membrane-spanning domains of yeast Lcb1p, located between residues 342 and 371
      and residues 425 and 457, respectively, create a luminal loop of approximately 60
      residues. In contrast to the first membrane-spanning domain, the second and third
      membrane-spanning domains were both required for Lcb1p stability. In addition,
      mutations in the luminal loop destabilized the SPT heterodimer indicating that
      this region of the protein is important for SPT structure and function. Mutations
      in the extreme carboxyl-terminal region of Lcb1p also disrupted heterodimer
      formation. Taken together, these data suggest that in contrast to other members
      of the alpha-oxoamine synthases that are soluble homodimers, the Lcb1p and Lcb2p
      subunits of the SPT heterodimer may interact in the cytosol, as well as within
      the membrane and/or the lumen of the endoplasmic reticulum.

PMID- 15485855
TI  - Diacylglycerol and its formation by phospholipase C regulate Rab- and SNARE
      dependent yeast vacuole fusion.
AB  - Although diacylglycerol (DAG) can trigger liposome fusion, biological membrane
      fusion requires Rab and SNARE proteins. We have investigated whether DAG and
      phosphoinositide-specific phospholipase C (PLC) have a role in the Rab- and SNARE
      dependent homo-typic vacuole fusion in Saccharomyces cerevisiae. Vacuole fusion
      was blocked when DAG was sequestered by a recombinant C1b domain. DAG underwent
      ATP-dependent turnover during vacuole fusion, but was replenished by the
      hydrolysis of phosphatidylinositol 4,5-bisphosphate to DAG by PLC. The PLC
      inhibitors 3-nitrocoumarin and U73122 blocked vacuole fusion in vitro, whereas
      their inactive homologues did not. Plc1p is the only known PLC in yeast. Yeast
      cells lacking the PLC1 gene have many small vacuoles, indicating defects in
      protein trafficking to the vacuole or vacuole fusion, and purified Plc1p
      stimulates vacuole fusion. Docking-dependent Ca(2+) efflux is absent in plc1Delta
      vacuoles and was restored only upon the addition of both Plc1p and the Vam7p
      SNARE. However, vacuoles purified from plc1Delta strains still retain PLC
      activity and significant 3-nitrocoumarin- and U73122-sensitive fusion, suggesting
      that there is another PLC in S. cerevisiae with an important role in vacuole
      fusion.

PMID- 15485856
TI  - Regulation of human beta-cell adhesion, motility, and insulin secretion by
      collagen IV and its receptor alpha1beta1.
AB  - Collagens have been shown to influence the survival and function of cultured beta
      cells; however, the utilization and function of individual collagen receptors in
      beta-cells is largely unknown. The integrin superfamily contains up to five
      collagen receptors, but we have determined that alpha(1)beta(1) is the primary
      receptor utilized by both fetal and adult beta-cells. Cultured beta-cells adhered
      to and migrated on collagen type IV (Col-IV), and these responses were mediated
      almost exclusively by alpha(1)beta(1). The migration of cultured beta-cells to
      Col-IV significantly exceeded that to other matrix components suggesting that
      this substrate is of unique importance for beta-cell motility. The interaction of
      alpha(1)beta(1) with Col-IV also resulted in significant insulin secretion at
      basal glucose concentrations. A subset of beta-cells in developing islets was
      confirmed to express alpha(1)beta(1), and this expression co-localized with Col
      IV in the basal membranes of juxtaposed endothelial cells. Our findings indicate
      that alpha(1)beta(1) and Col-IV contribute to beta-cell functions known to be
      important for islet morphogenesis and glucose homeostasis.

PMID- 15485857
TI  - Tissue transglutaminase is a multifunctional BH3-only protein.
AB  - Tissue transglutaminase (TG2) protein accumulates to high levels in cells during
      early stages of apoptosis both in vivo and in vitro. The analysis of the TG2
      primary sequence showed the presence of an eight amino acid domain, sharing 70%
      identity with the Bcl-2 family BH3 domain. Cell-permeable peptides, mimicking the
      domain sequence, were able to induce Bax conformational change and translocation
      to mitochondria, mitochondrial depolarization, release of cytochrome c, and cell
      death. Moreover, we found that the TG2-BH3 peptides as well as TG2 itself were
      able to interact with the pro-apoptotic Bcl-2 family member Bax, but not with
      anti-apoptotic members Bcl-2 and Bcl-X(L). Mutants in the TG2-BH3 domain failed
      to sensitize cells toward apoptosis. In TG2-overexpressing cells about half of
      the protein is localized on the outer mitochondrial membrane where, upon cell
      death induction, it cross-links many protein substrates including Bax. TG2 is the
      first member of a new subgroup of multifunctional BH3-only proteins showing a
      large mass size (80 kDa) and enzymatic activity.

PMID- 15485858
TI  - The phosphoinositol 3,4-bisphosphate-binding protein TAPP1 interacts with
      syntrophins and regulates actin cytoskeletal organization.
AB  - Syntrophins are scaffold proteins of the dystrophin glycoprotein complex (DGC),
      which target ion channels, receptors, and signaling proteins to specialized
      subcellular domains. A yeast two-hybrid screen of a human brain cDNA library with
      the PSD-95, Discs-large, ZO-1 (PDZ) domain of gamma1-syntrophin yielded
      overlapping clones encoding the C terminus of TAPP1, a pleckstrin homology (PH)
      domain-containing adapter protein that interacts specifically with
      phosphatidylinositol 3,4-bisphosphate (PI(3,4)P(2)). In biochemical assays, the C
      terminus of TAPP1 bound specifically to the PDZ domains of gamma1-, alpha1-, and
      beta2-syntrophin and was required for syntrophin binding and for the correct
      subcellular localization of TAPP1. TAPP1 is recruited to the plasma membrane of
      cells stimulated with platelet-derived growth factor (PDGF), a motogen that
      produces PI(3,4)P(2). Cell migration in response to PDGF stimulation is
      characterized by a rapid reorganization of the actin cytoskeleton, which gives
      rise to plasma membrane specializations including peripheral and dorsal circular
      ruffles. Both TAPP1 and syntrophins were localized to PDGF-induced circular
      membrane ruffles in NIH-3T3 cells. Ectopic expression of TAPP1 potently blocked
      PDGF-induced formation of dorsal circular ruffles, but did not affect peripheral
      ruffling. Interestingly, coexpression of alpha1- or gamma1-syntrophin with TAPP1
      prevented the blockade of circular ruffling. In addition to syntrophins, several
      other proteins of the DGC were enriched in circular ruffles. Collectively, our
      results suggest syntrophins regulate the localization of TAPP1, which may be
      important for remodeling the actin cytoskeleton in response to growth factor
      stimulation.

PMID- 15485859
TI  - Role of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) in
      distinct and overlapping CD40 and TNF receptor 2/CD120b-mediated B lymphocyte
      activation.
AB  - Members of the tumor necrosis factor receptor (TNFR) family play a variety of
      roles in the regulation of lymphocyte activation. An important TNFR family member
      for B cell activation is CD40. CD40 signals stimulate B cell TNF-alpha secretion,
      which subsequently signals via TNFR2 (CD120b) to enhance B cell activation.
      Although the function of the pro-apoptotic and pro-inflammatory receptor TNFR1
      (CD120a) has been the subject of much research, less is understood about the
      distinct contributions of CD120b to cell activation and how it stimulates
      downstream events. Members of the tumor necrosis factor receptor family bind
      various members of the cytoplasmic adapter protein family, the tumor necrosis
      factor receptor-associated factors (TRAFs), during signaling. Both CD40 and
      CD120b bind TNF receptor-associated factor 2 (TRAF2) upon ligand stimulation.
      Wild type and TRAF2-deficient B cells expressing CD40 or the hybrid molecule
      (human) CD40 (mouse)-CD120b were examined. CD40- and CD120b-mediated IgM
      secretion were partly TRAF2-dependent, but only CD40 required TRAF2 for c-Jun N
      terminal kinase activation. CD40 and CD120b used primarily divergent mechanisms
      to activate NF-kappaB, exemplifying how TNFR family members can use diverse
      mechanisms to mediate similar downstream events.

PMID- 15485860
TI  - Characterization of the histone acetyltransferase (HAT) domain of a bifunctional
      protein with activable O-GlcNAcase and HAT activities.
AB  - Histones and transcription factors are regulated by a number of post
      translational modifications that in turn regulate the transcriptional activity of
      genes. These modifications occur in large, multisubunit complexes. We have
      reported previously that mSin3A can recruit O-GlcNAc transferase (OGT) along with
      histone deacetylase into such a corepressor complex. This physical association
      allows OGT to act cooperatively with histone deacetylation in gene repression by
      catalyzing the O-GlcNAc modification on specific transcription factors to inhibit
      their activity. For rapid, reversible gene regulation, the enzymes responsible
      for the converse reactions must be present. Here, we report that O-GlcNAcase,
      which is responsible for the removal of O-GlcNAc additions on nuclear and
      cytosolic proteins, possesses intrinsic histone acetyltransferase (HAT) activity
      in vitro. Free as well as reconstituted nucleosomal histones are substrates of
      this bifunctional enzyme. This protein, now termed NCOAT (nuclear cytoplasmic O
      GlcNAcase and acetyltransferase) has a typical HAT domain that has both active
      and inactive states. This finding demonstrates that NCOAT may be regulated to
      reduce the state of glycosylation of transcriptional activators while increasing
      the acetylation of histones to allow for the concerted activation of eukaryotic
      gene transcription.

PMID- 15485861
TI  - Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through
      the down-regulation of telomerase.
AB  - The maintenance of telomere length is required for continued cell proliferation,
      and approximately 85-90% of human cancers, including ovarian epithelial cancers
      (OCa), show high activity of telomerase. In the present study we report that 1,25
      dihydroxyvitamin D(3) (1,25(OH)(2) VD)(3)induces OCa cell apoptosis by down
      regulating telomerase. Quantitative reverse transcription-PCR analysis shows that
      1,25(OH)(2)VD(3) decreases the level of human telomerase reverse transcriptase
      (hTERT) mRNA, the catalytic subunit of telomerase. The decrease is not due to
      transcriptional repression through the putative vitamin D response element
      present in the 5' regulatory region of hTERT gene. Instead, 1,25(OH)(2) VD(3)
      decreases the stability of the hTERT mRNA. Stable expression of hTERT in OCa
      cells decreases their response to 1,25(OH)(2)VD(3)-induced growth suppression.
      Although the cell cycle progression of these clones stably expressing hTERT is
      inhibited by 1,25(OH)(2)VD(3) to a similar degree as that of the parental cells,
      these clones are more resistant to apoptosis induced by 1,25(OH)(2)VD(3) .In
      contrast to parental cells, which lose proliferation potential after the
      1,25(OH)(2)VD(3) treatment, hTERT-expressing clones resume rapid growth after
      withdrawal of 1,25(OH)(2)VD(3). Overall, the study suggests that the down
      regulation of telomerase activity by 1,25(OH)(2)VD(3) and the resulting cell
      death are important components of the response of OCa cells to 1,25(OH)(2)VD(3)
      induced growth suppression.

PMID- 15485862
TI  - Dimerization of beta-site beta-amyloid precursor protein-cleaving enzyme.
AB  - Cleavage of the beta-amyloid precursor protein (APP) by the aspartyl protease
      beta-site APP-cleaving enzyme (BACE) is the first step in the generation of the
      amyloid beta-peptide, which is deposited in the brain of Alzheimer's disease
      patients. Whereas the subsequent cleavage by gamma-secretase was shown to
      originate from the cooperation of a multicomponent complex, it is currently
      unknown whether in a cellular environment BACE is enzymatically active as a
      monomer or in concert with other proteins. Using blue native gel electrophoresis
      we found that endogenous and overexpressed BACE has a molecular mass of 140 kDa
      instead of the expected mass of 70 kDa under denaturing conditions. This suggests
      that under native conditions BACE exists as a homodimer. Homodimerization was
      confirmed by co-immunoprecipitation of full-length BACE carrying different
      epitope tags. In contrast, the soluble active BACE ectodomain was exclusively
      present as a monomer both under native and denaturing conditions. A domain
      analysis revealed that the BACE ectodomain dimerized as long as it was attached
      to the membrane, whereas the cytoplasmic domain and the transmembrane domain were
      dispensable for dimerization. By adding a KKXX-endoplasmic reticulum retention
      signal to BACE, we demonstrate that dimerization of BACE occurs already before
      full maturation and pro-peptide cleavage. Furthermore, kinetic analysis of the
      purified native BACE dimer revealed a higher affinity and turnover rate in
      comparison to the monomeric soluble BACE. Dimerization of BACE might, thus,
      facilitate binding and cleavage of physiological substrates.

PMID- 15485863
TI  - Many amino acid substitutions in a hypoxia-inducible transcription factor (HIF)
      1alpha-like peptide cause only minor changes in its hydroxylation by the HIF
      prolyl 4-hydroxylases: substitution of 3,4-dehydroproline or azetidine-2
      carboxylic acid for the proline leads to a high rate of uncoupled 2-oxoglutarate
      decarboxylation.
AB  - Three human prolyl 4-hydroxylases (P4Hs) regulate the hypoxia-inducible
      transcription factors (HIFs) by hydroxylating a Leu-Xaa-Xaa-Leu-Ala-Pro motif. We
      report here that the two leucines in the Leu-Glu-Met-Leu-Ala-Pro core motif of a
      20-residue peptide corresponding to the sequence around Pro(564) in HIF-1alpha
      can be replaced by many residues with no or only a modest decrease in its
      substrate properties or in some cases even a slight increase. The glutamate and
      methionine could be substituted by almost any residue, eight amino acids in the
      former position and four in the latter being even better for HIF-P4H-3 than the
      wild-type residues. Alanine was by far the strictest requirement, because no
      residue could fully substitute for it in the case of HIF-P4H-1, and only serine
      or isoleucine, valine, and serine did this in the cases of HIF-P4Hs 2 and 3.
      Peptides with more than one substitution, having the core sequences Trp-Glu-Met
      Val-Ala-Pro, Tyr-Glu-Met-Ile-Ala-Pro, Ile-Glu-Met-Ile-Ala-Pro, Trp-Glu-Met-Val
      Ser-Pro, and Trp-Glu-Ala-Val-Ser-Pro were in most cases equally as good or almost
      as good substrates as the wild-type peptide. The acidic residues present in the
      20-residue peptide also played a distinct role, but alanine substitution for any
      six of them, and in some combinations even three of them, had no negative
      effects. Substitution of the proline by 3,4-dehydroproline or l-azetidine-2
      carboxylic acid, but not any other residue, led to a high rate of uncoupled 2
      oxoglutarate decarboxylation with no hydroxylation. The data obtained for the
      three HIF-P4Hs in various experiments were in most cases similar, but in some
      cases HIF-P4H-3 showed distinctly different properties.

PMID- 15485864
TI  - Functional consequences of alterations to Thr247, Pro248, Glu340, Asp813, Arg819,
      and Arg822 at the interfaces between domain P, M3, and L6-7 of sarcoplasmic
      reticulum Ca2+-ATPase. Roles in Ca2+ interaction and phosphoenzyme processing.
AB  - Point mutants with alterations to amino acid residues Thr(247), Pro(248),
      Glu(340), Asp(813), Arg(819), and Arg(822) of sarcoplasmic reticulum Ca(2+)
      ATPase were analyzed by transient kinetic measurements. In the Ca(2+)-ATPase
      crystal structures, most of these residues participate in a hydrogen-bonding
      network between the phosphorylation domain (domain P), the third transmembrane
      helix (M3), and the cytoplasmic loop connecting the sixth and the seventh
      transmembrane helices (L6-7). In several of the mutants, a pronounced
      phosphorylation "overshoot" was observed upon reaction of the Ca(2+)-bound enzyme
      with ATP, because of accumulation of dephosphoenzyme at steady state. Mutations
      of Glu(340) and its partners, Thr(247) and Arg(822), in the bonding network
      markedly slowed the Ca(2+) binding transition (E2 --> E1 --> Ca(2)E1) as well as
      Ca(2+) dissociation from Ca(2+) site II back toward the cytosol but did not
      affect the apparent affinity for vanadate. These mutations may have caused a
      slowing, in both directions, of the conformational change associated directly
      with Ca(2+) interaction at Ca(2+) site II. Because mutation of Asp(813) inhibited
      the Ca(2+) binding transition, but not Ca(2+) dissociation, and increased the
      apparent affinity for vanadate, the effect on the Ca(2+) binding transition seems
      in this case to be exerted by slowing the E2 --> E1 conformational change.
      Because the rate was not significantly enhanced by a 10-fold increase of the
      Ca(2+) concentration, the slowing is not the consequence of reduced affinity of
      any pre-binding site for Ca(2+). Furthermore, the mutations interfered in
      specific ways with the phosphoenzyme processing steps of the transport cycle; the
      transition from ADP-sensitive phosphoenzyme to ADP-insensitive phosphoenzyme
      (Ca(2)E1P --> E2P) was accelerated by mutations perturbing the interactions
      mediated by Glu(340) and Asp(813) and inhibited by mutation of Pro(248), and
      mutations of Thr(247) induced charge-specific changes of the rate of
      dephosphorylation of E2P.

PMID- 15485865
TI  - G16-mediated activation of nuclear factor kappaB by the adenosine A1 receptor
      involves c-Src, protein kinase C, and ERK signaling.
AB  - The G(i)-linked adenosine A1 receptor has been shown to mediate anti-inflammatory
      actions, possibly via modulation of the transcription factor nuclear factor
      kappaB (NFkappaB). Here we demonstrate that an adenosine A1 agonist, N(6)
      cyclohexyladenosine (CHA), activated IKKalpha/beta phosphorylation through PTX
      insensitive G proteins in human lymphoblastoma Reh cells. To delineate the
      mechanism of action, different PTX-insensitive G proteins were expressed in human
      embryonic kidney 293 cells. Only Galpha(16) supported the CHA-induced IKK
      phosphorylation and NFkappaB-driven luciferase activity in time-dependent, dose
      dependent, and PTX-insensitive manners. Gbetagamma subunits also modulated
      IKK/NFkappaB, as indicated by the stimulatory actions of Gbeta(1)gamma(2) and the
      abrogation of CHA-induced response by transducin. The participation of
      phospholipase Cbeta, protein kinase C, and calmodulin-dependent kinase II in CHA
      induced IKK/NFkappaB activation were demonstrated by employing specific
      inhibitors and dominant-negative mutants. Inhibition of c-Src and numerous
      intermediates along the extracellular signal-regulated (ERK) kinase cascade
      including Ras, Raf-1 kinase, and MEK1/2 abolished the CHA-induced IKK/NFkappaB
      activation. Although c-Jun N-terminal kinase and p38 MAPK were also activated by
      CHA, they were not required for the IKK/NFkappaB regulation. Similar results were
      obtained using Reh cells. These data suggest that the G(16)-mediated activation
      of IKK/NFkappaB by CHA required a complex signaling network composed of multiple
      intermediates.

PMID- 15485866
TI  - Sphingosine kinase 1 (SPHK1) is induced by transforming growth factor-beta and
      mediates TIMP-1 up-regulation.
AB  - Transforming growth factor-beta (TGF-beta) signaling plays a pivotal role in
      extracellular matrix deposition by stimulating collagen production and other
      extracellular matrix proteins and by inhibiting matrix degradation. The present
      study was undertaken to define the role of sphingosine kinase (SphK) in TGF-beta
      signaling. TGF-beta markedly up-regulated SphK1 mRNA and protein amounts and
      caused a prolonged increase in SphK activity in dermal fibroblasts.
      Concomitantly, TGF-beta reduced sphingosine-1-phosphate phosphatase activity.
      Consistent with the changes in enzyme activity, corresponding changes in
      sphingolipid levels were observed such that sphingosine 1-phosphate (S1P) was
      increased (approximately 2-fold), whereas sphingosine and ceramide were reduced
      after 24 h of TGF-beta treatment. Given the relatively early induction of SphK
      gene expression in response to TGF-beta, we examined whether SphK1 may be
      involved in the regulation of TGF-beta-inducible genes that exhibit compatible
      kinetics, e.g. tissue inhibitor of metalloproteinase-1 (TIMP-1). We demonstrate
      that decreasing SphK1 expression by small interfering RNA (siRNA) blocked TGF
      beta-mediated up-regulation of TIMP-1 protein suggesting that up-regulation of
      SphK1 contributes to the induction of TIMP-1 in response to TGF-beta. The role of
      SphK1 as a positive regulator of TIMP-1 gene expression was further corroborated
      by using ectopically expressed SphK1 in the absence of TGF-beta. Adenovirally
      expressed SphK1 led to a 2-fold increase of endogenous S1P and to increased TIMP
      1 mRNA and protein production. In addition, ectopic SphK1 and TGF-beta cooperated
      in TIMP-1 up-regulation. Mechanistically, experiments utilizing TIMP-1 promoter
      constructs demonstrated that the action of SphK1 on the TIMP-1 promoter is
      through the AP1-response element, consistent with the SphK1-mediated up
      regulation of phospho-c-Jun levels, a key component of AP1. Together, these
      experiments demonstrate that SphK/S1P are important components of the TGF-beta
      signaling pathway involved in up-regulation of the TIMP-1 gene.

PMID- 15485867
TI  - Hairy-related transcription factors inhibit GATA-dependent cardiac gene
      expression through a signal-responsive mechanism.
AB  - Combinatorial actions of transcription factors in multiprotein complexes dictate
      gene expression profiles in cardiac development and disease. The Hairy-related
      transcription factor (HRT) family of basic helix-loop-helix proteins is composed
      of transcriptional repressors highly expressed in the cardiovascular system.
      However, it has remained unclear whether HRT proteins modulate gene expression
      driven by cardiac transcriptional activators. Here, we have shown that HRT
      proteins inhibit cardiac gene transcription by interfering with GATA
      transcription factors that are implicated in cardiac development and hypertrophy.
      HRT proteins inhibited GATA-dependent transcriptional activation of cardiac gene
      promoters such as the atrial natriuretic factor (ANF) promoter. Adenovirus
      mediated expression of Hrt2 suppressed mRNA expression of ANF and other cardiac
      specific genes in cultured cardiomyocytes. Among various signaling molecules
      implicated in cardiomyocyte growth, constitutively active Akt1/protein kinase B
      alpha relieved Hrt2-mediated inhibition of GATA-dependent transcription. HRT
      proteins physically interacted with GATA proteins, and the basic domain of HRT
      was critical for physical association as well as transcriptional inhibition.
      These results suggest that HRT proteins may regulate specific sets of cardiac
      genes by modulating the function of GATA proteins and other cardiac
      transcriptional activators in a signal-dependent manner.

PMID- 15485868
TI  - A novel strategy for defining critical amino acid residues involved in
      protein/glycosaminoglycan interactions.
AB  - The binding of proteins to glycosaminoglycans (GAGs) is the prerequisite for a
      large number of cellular processes and regulatory events and is associated to
      many pathologies. However, progress in the understanding of these mechanisms has
      been hampered by the lack of simple and comprehensive analytical tools for the
      identification of the structural attributes involved in protein/saccharide
      interaction. Characterization of GAG binding motifs on proteins has so far relied
      on site-directed mutagenesis studies, protein sequence mapping using synthetic
      peptides, molecular modeling, or structural analysis. Here, we report the
      development of a novel approach for identifying protein residues involved in the
      binding to heparin, the archetypal member of the GAG family. This method, which
      uses native proteins, is based on the formation of cross-linked complexes of the
      protein of interest with heparin beads, the proteolytic digestion of these
      complexes, and the subsequent identification of the heparin binding containing
      peptides by N terminus sequencing. Analysis of the CC chemokine regulated on
      activation, normal T-cell expressed, and secreted (RANTES), the envelope
      glycoprotein gC from pseudorabies virus and the laminin-5 alpha 3LG4/5 domain
      validated the techniques and provided novel information on the heparin binding
      motifs present within these proteins. Our results highlighted this method as a
      fast and valuable alternative to existing approaches. Application of this
      technique should greatly contribute to facilitate the structural study of
      protein/GAG interactions and the understanding of their biological functions.

PMID- 15485869
TI  - Dissociation of human copper-zinc superoxide dismutase dimers using chaotrope and
      reductant. Insights into the molecular basis for dimer stability.
AB  - The dissociation of apo- and metal-bound human copper-zinc superoxide dismutase
      (SOD1) dimers induced by the chaotrope guanidine hydrochloride (GdnHCl) or the
      reductant Tris(2-carboxyethyl)phosphine (TCEP) has been analyzed using analytical
      ultracentrifugation. Global fitting of sedimentation equilibrium data under
      native solution conditions (without GdnHCl or TCEP) demonstrate that both the apo
      and metal-bound forms of SOD1 are stable dimers. Sedimentation velocity
      experiments show that apo-SOD1 dimers dissociate cooperatively over the range 0.5
      1.0 M GdnHCl. In contrast, metal-bound SOD1 dimers possess a more compact shape
      and dissociate at significantly higher GdnHCl concentrations (2.0-3.0 M).
      Reduction of the intrasubunit disulfide bond within each SOD1 subunit by 5-10 mM
      TCEP promotes dissociation of apo-SOD1 dimers, whereas the metal-bound enzyme
      remains a stable dimer under these conditions. The Cys-57 --> Ser mutant of SOD1,
      a protein incapable of forming the intrasubunit disulfide bond, sediments as a
      monomer in the absence of metal ions and as a dimer when metals are bound. Taken
      together, these data indicate that the stability imparted to the human SOD1 dimer
      by metal binding and the formation of the intrasubunit disulfide bond are
      mediated by independent molecular mechanisms. By combining the sedimentation data
      with previous crystallographic results, a molecular explanation is provided for
      the existence of different SOD1 macromolecular shapes and multiple SOD1 dimeric
      species with different stabilities.

PMID- 15485871
TI  - Bcl-2 and Bax exert opposing effects on Ca2+ signaling, which do not depend on
      their putative pore-forming region.
AB  - Recent work has shown that Bcl-2 and other anti-apoptotic proteins partially
      deplete the endoplasmic reticulum (ER) Ca(2+) store and that this alteration of
      Ca(2+) signaling reduces cellular sensitivity to apoptotic stimuli. We expressed
      in HeLa cells Bcl-2, Bax, and Bcl-2/Bax chimeras in which the putative pore
      forming domains of the two proteins (alpha 5-alpha 6) were mutually swapped,
      comparing the effects on Ca(2+) signaling of the two proteins and relating them
      to defined molecular domains. The results showed that only Bcl-2 reduces ER
      Ca(2+) levels and that this effect does not depend on the alpha 5-alpha 6 helices
      of this oncoprotein. Soon after its expression, Bax increased ER Ca(2+) loading,
      with ensuing potentiation of mitochondrial Ca(2+) responses. Then the cells
      progressed into an apoptotic phenotype (which included drastic reductions of
      cytosolic and mitochondrial Ca(2+) responses and alterations of organelle
      morphology). These results provide a coherent scenario that high-lights a primary
      role of Ca(2+) signals in deciphering apoptotic stimuli.

PMID- 15485870
TI  - KChIP3 rescues the functional expression of Shal channel tetramerization mutants.
AB  - KChIP proteins regulate Shal, Kv4.x, channel expression by binding to a conserved
      sequence at the N terminus of the subunit. The binding of KChIP facilitates a
      redistribution of Kv4 protein to the cell surface, producing a large increase in
      current along with significant changes in channel gating kinetics. Recently we
      have shown that mutants of Kv4.2 lacking the ability to bind an intersubunit
      Zn(2+) between their T1 domains fail to form functional channels because they are
      unable to assemble to tetramers and remain trapped in the endoplasmic reticulum.
      Here we find that KChIPs are capable of rescuing the function of Zn(2+) site
      mutants by driving the mutant subunits to assemble to tetramers. Thus, in
      addition to known trafficking effects, KChIPs play a direct role in subunit
      assembly by binding to monomeric subunits within the endoplasmic reticulum and
      promoting tetrameric channel assembly. Zn(2+)-less Kv4.2 channels expressed with
      KChIP3 demonstrate several distinct kinetic changes in channel gating, including
      a reduced time to peak and faster entry into the inactivated state as well as
      extending the time to recover from inactivation by 3-4 fold.

PMID- 15485872
TI  - Nematode chondroitin polymerizing factor showing cell-/organ-specific expression
      is indispensable for chondroitin synthesis and embryonic cell division.
AB  - Chondroitin polymerization was first demonstrated in vitro when human chondroitin
      synthase (ChSy) was coexpressed with human chondroitin polymerizing factor
      (ChPF), which is homologous to ChSy but has little glycosyltransferase activity.
      To analyze the biological function of chondroitin, the Caenorhabditis elegans
      ortholog of human ChSy (sqv-5) was recently cloned, and the expression of its
      product was depleted by RNA-mediated interference (RNAi) and deletion
      mutagenesis. Blocking of chondroitin synthesis resulted in defects of cytokinesis
      in early embryogenesis, and eventually, cell division stopped. Here, we cloned
      the ortholog of human ChPF in C. elegans, PAR2.4. Despite little
      glycosyltransferase activity of the gene product, chondroitin polymerization was
      demonstrated as in the case of mammals when PAR2.4 was coexpressed with cChSy in
      vitro. The worm phenotypes including the reversion of cytokinesis, observed after
      the depletion of PAR2.4 by RNAi, were very similar to the cChSy (sqv-5)-RNAi
      phenotypes. Thus, PAR2.4 in addition to cChSy is indispensable for the
      biosynthesis of chondroitin in C. elegans, and the two cooperate to synthesize
      chondroitin in vivo. The expression of the PAR2.4 protein was observed in seam
      cells, which can act as neural stem cells in early embryonic lineages. The
      expression was also detected in vulva and distal tip cells of the growing gonad
      arms from L3 through to the young adult stage. These findings are consistent with
      the notion that chondroitin is involved in the organogenesis of the vulva and
      maturation of the gonad and also indicative of an involvement in distal tip cell
      migration and neural development.

PMID- 15485873
TI  - Identification and characterization of a gene encoding human LPGAT1, an
      endoplasmic reticulum-associated lysophosphatidylglycerol acyltransferase.
AB  - Phosphatidylglycerol (PG) is an important membrane polyglycerolphospholipid
      required for the activity of a variety of enzymes and is a precursor for
      synthesis of cardiolipin and bis(monoacylglycerol) phosphate. PG is subjected to
      remodeling subsequent to its de novo biosynthesis to incorporate appropriate acyl
      content for its biological functions and to prevent the harmful effect of
      lysophosphatidylglycerol (LPG) accumulation. The enzymes involved in the
      remodeling process have not yet been identified. We report here the
      identification and characterization of a human gene encoding an acyl-CoA:
      lysophosphatidylglycerol acyltransferase (LPGAT1). Expression of the LPGAT1 cDNA
      in Sf9 insect and COS-7 cells led to a significant increase in LPG
      acyltransferase activity. In contrast, no significant acyltransferase activities
      were detected against glycerol 3-phosphate or a variety of lysophospholipids,
      including lysophosphatidylcholine, lysophosphatidylethanolamine,
      lysophosphatidylinositol, and lysophosphatidylserine. The recombinant human
      LPGAT1 enzyme recognized various acyl-CoAs and LPGs as substrates but
      demonstrated clear preference to long chain saturated fatty acyl-CoAs and oleoyl
      CoA as acyl donors, which is consistent with the lipid composition of endogenous
      PGs identified from different tissues. Kinetic analyses of LPGAT1 expressed in
      COS-7 cells showed that oleoyl-LPG was preferred over palmitoyl-LPG as an acyl
      receptor, whereas oleoyl-CoA was preferred over lauroyl-CoA as an acyl donor.
      Consistent with its proposed microsomal origin, LPGAT1 was localized to the
      endoplasmic reticulum by subcellular fractionation and immunohistochemical
      analyses. Northern blot analysis indicated that the human LPGAT1 was widely
      distributed, suggesting a dynamic functional role of the enzyme in different
      tissues.

PMID- 15485874
TI  - Biochemical and cell biological analyses of a mammalian septin complex,
      Sept7/9b/11.
AB  - Septins are members of a conserved family of cytoskeletal GTPases present in
      organisms as diverse as yeast and mammals. Unlike lower eukaryotic cells, the
      physiological significance of mammalian septin complexes is largely unknown.
      Using specific antibodies, we found at least five septins, Sept2, Sept7, Sept8,
      Sept9b, and Sept11, in septin complexes affinity-purified with anti-Sept7
      antibody-conjugated column from rat embryonic fibroblast REF52 cells.
      Immunofluorescence studies revealed co-localization of Sept7, Sept9b, and Sept11
      along stress fibers in REF52 cells. Biochemical and immunoprecipitation analyses
      revealed that the three septins directly bind with each other through their N- or
      C-terminal divergent regions. These septins per se formed distinct and
      characteristic filament structures when transiently expressed in COS7 cells. When
      two of the three septins were co-expressed in COS7 cells, combination-dependent
      filament elongation, bundling, or disruption was observed. Taken together, our
      results suggest that septin filament structures may be affected by interactions
      with other septins included in the complex.

PMID- 15485875
TI  - Nuclear orphan receptor Nurr1 directly transactivates the osteocalcin gene in
      osteoblasts.
AB  - Nurr1, an NGFI-B nuclear orphan receptor, which transactivates promoters through
      an NGFI-B response element (NBRE), is strongly induced by parathyroid hormone
      through the cAMP-protein kinase A signaling pathway in osteoblasts. Here, we
      demonstrate that multiple agents activating diverse signaling pathways in
      osteoblasts induce Nurr1. The strongest Nurr1 inducers were activators of cAMP
      protein kinase A-coupled signaling, followed by protein kinase C- and calcium
      coupled signaling activators. Receptor tyrosine kinase activators had minimal
      effect, whereas serine/threonine kinase activators had no effect on basal Nurr1
      mRNA levels. Computer analysis of osteoblastic promoters indicated two potential
      NBREs in the rat osteocalcin (Ocn) promoter. Intriguingly, the proximal site maps
      to the cAMP-responsive cis-element. We tested whether Nurr1 induces Ocn
      expression through the NBRE-like site. Recombinant and endogenous Nurr1 protein
      from primary mouse osteoblasts bound to a consensus NBRE in EMSAs. Nurr1 induced
      a consensus 3 x NBRE-luciferase reporter construct in mouse osteoblasts.
      Recombinant and endogenous Nurr1 protein bound to the proximal NBRE-like site in
      the Ocn promoter in EMSAs. Endogenous Nurr1 protein bound to this site as a
      monomer, because neither retinoid X receptor alpha nor retinoid X receptor beta
      antibody supershifted the protein-DNA complex. Ocn promoter-luciferase constructs
      lacking or containing a mutated proximal NBRE-like site had markedly blunted
      responses to Nurr1 overexpression. Finally, adenovirally expressed Nurr1 protein
      bound to the proximal NBRE-like site in chromatin immunoprecipitation assays and
      induced Ocn mRNA in primary rat osteoblasts. We conclude that Ocn is a Nurr1
      target gene, which positions Nurr1 in the core of transcriptional factors
      regulating osteoblastic gene expression.

PMID- 15485876
TI  - Adenoviral overexpression of the glutamylcysteine ligase catalytic subunit
      protects pancreatic islets against oxidative stress.
AB  - The catalytic subunit of glutamylcysteine ligase (GCLC) primarily regulates de
      novo synthesis of glutathione (GSH) in mammalian cells and is central to the
      antioxidant capacity of the cell. However, GCLC expression in pancreatic islets
      has not been previously examined. We designed experiments to ascertain whether
      GCLC is normally expressed in islets and whether it is up-regulated by
      interleukin-1 beta (IL-1 beta). GCLC expression levels were intermediate compared
      with other metabolic tissues (kidney, liver, muscle, fat, and lung). IL-1 beta up
      regulated GCLC expression (10 ng/ml IL-1 beta, 3.76 +/- 0.86; 100 ng/ml IL-1
      beta, 4.22 +/- 0.68-fold control) via the p38 form of mitogen-activated protein
      kinase and NF kappa B and also increased reactive oxygen species levels (10 ng/ml
      IL-1 beta, 5.41 +/- 1.8-fold control). This was accompanied by an increase in
      intraislet GSH/GSSG ratio (control, 7.1 +/- 0.1; 10 ng/ml IL-1 beta, 8.0 +/- 0.5;
      100 ng/ml IL-1 beta, 8.2 +/- 0.5-fold control; p < 0.05). To determine whether
      overexpression of GCLC increases the antioxidant capacity of the islet and
      prevents the adverse effects of IL-1 beta on glucose-induced insulin secretion,
      islets were infected with an adenovirus encoding GCLC. IL-1 beta significantly
      decreased glucose-stimulated insulin secretion (control, 123.8 +/- 17.7; IL-1
      beta, 40.2 +/- 3.9 microunits/ml insulin/islet). GCLC overexpression increased
      intraislet GSH levels and partially prevented the decrease in glucose-stimulated
      insulin secretion caused by IL-1 beta. These data provide the first report of
      GCLC expression in the islet and demonstrate that adenoviral overexpression of
      GCLC increases intracellular GSH levels and protects the beta cell from the
      adverse effects of IL-1 beta.

PMID- 15485877
TI  - Molecular mechanisms of low intensity pulsed ultrasound in human skin
      fibroblasts.
AB  - Soluble factors such as polypeptide growth factors, mitogenic lipids,
      inflammatory cytokines, and hormones are known regulators of cell proliferation.
      However, the effect of mechanical stimuli on cell proliferation is less well
      understood. Here we examined the effect of low intensity pulsed ultrasound (US),
      which is used to promote wound healing, on the proliferation of primary human
      foreskin fibroblasts and the underlying signaling mechanisms. We show that a
      single 6-11-min US stimulation increases bromodeoxyuridine incorporation. In
      addition, an increase in the total cell number is observed after sequential US
      stimulation. US induced stress fiber and focal adhesion formation via activation
      of Rho. We further observed that US selectively induced activation of
      extracellular signal-regulated kinase (ERK) 1/2. Inhibition of Rho-associated
      coiled-coil-containing protein kinase (ROCK) prevented US-induced ERK1/2
      activation, demonstrating that the Rho/ROCK pathway is an upstream regulator of
      ERK activation in response to US. Consequently, activation of ROCK and MEK-1 was
      required for US-induced DNA synthesis. Finally, an integrin beta(1) blocking
      antibody as well as a RGD peptide prevented US-induced DNA synthesis. In
      addition, US slightly increased phosphorylation of Src at Tyr(416), and Src
      activity was found to be required for ERK1/2 activation in response to US. In
      conclusion, our data demonstrate for the first time that US promotes cell
      proliferation via activation of integrin receptors and a Rho/ROCK/Src/ERK
      signaling pathway.

PMID- 15485878
TI  - Functional identification of three receptor activator of NF-kappa B cytoplasmic
      motifs mediating osteoclast differentiation and function.
AB  - Receptor activator of NF-kappa B ligand (RANKL) and its receptor activator of NF
      kappa B (RANK) play pivotal roles in osteoclast differentiation and function.
      However, the structural determinants of the RANK that mediate osteoclast
      formation and function have not been definitively identified. To address this
      issue, we developed a chimeric receptor approach that permits a
      structure/function study of the RANK cytoplasmic domain in osteoclasts. Using
      this approach, we examined the role of six RANK putative tumor necrosis factor
      receptor-associated factor-binding motifs (PTM) (PTM1, ILLMT-REE(286-293); PTM2,
      PSQPS(349-353); PTM3, PFQEP(369-373); PTM4, VYVSQTSQE(537-545); PTM5, PVQEET(559
      564); and PTM6, PVQEQG(604-609)) in osteoclast formation and function. Our data
      revealed that the RANK cytoplasmic domain possesses three functional motifs
      (PFQEP(369-373), PVQEET(559-564), and PVQEQG(604-609)) capable of mediating
      osteoclast formation and function. Moreover, we demonstrated that these motifs
      play distinct roles in activating intracellular signaling. PFQEP(369-373)
      initiates NF-kappa B, c-Jun N-terminal kinase, extracellular signal-regulated
      kinase, and p38 signaling pathways and PVQEET(559-564) activates NF-kappa B and
      p38 pathways in osteoclasts, whereas PVQEQG(604-609) is only capable of
      activating NF-kappa B pathway. Significantly, the revelation of these functional
      RANK cytoplasmic motifs has not only laid a foundation for further delineating
      RANK signaling pathways in osteoclasts, but, more importantly, these RANK motifs
      themselves represent potential therapeutic targets for bone disorders such as
      osteoporosis.

PMID- 15485879
TI  - Phosphorylation of annexin I by TRPM7 channel-kinase.
AB  - TRPM7 is an unusual bifunctional molecule consisting of a TRP ion channel fused
      to a protein kinase domain. It has been shown that TRPM7 plays a key role in the
      regulation of intracellular magnesium homeostasis as well as in anoxic neuronal
      death. TRPM7 channel has been characterized using electrophysiological
      techniques; however, the function of the kinase domain is not known and
      endogenous substrates for the kinase have not been reported previously. Here we
      have identified annexin 1 as a substrate for TRPM7 kinase. Phosphorylation of
      annexin 1 by TRPM7 kinase is stimulated by Ca2+ and is dramatically increased in
      extracts from cells overexpressing TRPM7. Phosphorylation of annexin 1 by TRPM7
      kinase occurs at a conserved serine residue (Ser5) located within the N-terminal
      amphipathic alpha-helix of annexin 1. The N-terminal region plays a crucial role
      in interaction of annexin 1 with other proteins and membranes, and therefore,
      phosphorylation of annexin 1 at Ser5 by TRPM7 kinase may modulate function of
      annexin 1.

PMID- 15485880
TI  - Role of N- and C-terminal residues of insulin-like growth factor (IGF)-binding
      protein-3 in regulating IGF complex formation and receptor activation.
AB  - Insulin-like growth factor-binding protein-3 (IGFBP-3), the major IGFBP in the
      circulation, sequesters IGF in a stable ternary complex with the acid-labile
      subunit. The high affinity IGF-binding site is proposed to reside within an N
      terminal hydrophobic domain in IGFBP-3, but C-terminal residues have also been
      implicated in the homologous protein IGFBP-5. We have mutated in various
      combinations Leu(77), Leu(80), and Leu(81) in the N terminus and Gly(217) and
      Gln(223) in the C terminus of IGF-BP-3. All mutants retained immunoreactivity
      toward a polyclonal IGFBP-3 antibody, whereas IGF ligand blotting showed that all
      of the mutants had reduced binding to IGFs. Both solution IGF binding assays and
      BIAcore analysis indicated that mutations to the N-terminal region caused greater
      reduction in IGF binding activity than C-terminal mutations. The combined N- and
      C-terminal mutants showed undetectable binding to IGF-I but retained <10% IGF-II
      binding activity. Reduced ternary complex formation was seen only in mutants that
      had considerably reduced IGF-I binding, consistent with previous studies
      indicating that the binary IGF.IGFBP-3 complex is required for acid-labile
      subunit binding. Decreased IGF binding was also reflected in the inability of the
      mutants to inhibit IGF-I signaling in IGF receptor overexpressing cells. However,
      when present in excess, IGFBP-3 analogs defined as non-IGF-binding by biochemical
      assays could still inhibit IGF signaling. This suggests that residual binding
      activity of IGFBP-3 mutants may still be sufficient to inhibit IGF biological
      activity and questions the use of such analogs to study IGF-independent effects
      of IGFBP-3.

PMID- 15485881
TI  - Impaired recycling of apolipoprotein E4 is associated with intracellular
      cholesterol accumulation.
AB  - After internalization of triglyceride-rich lipoproteins (TRL) in hepatoma cells,
      TRL particles are immediately disintegrated in the early endosomal compartment.
      This involves the targeting of lipids and apoprotein B along the degradative
      pathway and the recycling of TRL-derived apoE through recycling endosomes. Re
      secretion of apoE is accompanied by the concomitant association of apoE and
      cellular cholesterol with high-density lipoproteins (HDL). Since epidemiological
      data showed that apoE3 and apoE4 have differential effects on HDL metabolism, we
      investigated whether the intracellular processing of TRL-derived apoE4 differs
      from apoE3-TRL. In this study, we demonstrated by radioactive and
      immunofluorescence uptake experiments that cell-surface binding and
      internalization of TRL-derived apoE4 are increased compared with apoE3 in
      hepatoma cells. Pulse-chase experiments revealed that HDL-induced recycling, but
      not disintegration and degradation, of apoE4-enriched TRL is strongly reduced in
      these cells. Furthermore, impaired HDL-induced apoE4 recycling is associated with
      reduced cholesterol efflux. Studies performed in Tangier fibroblasts showed that
      apoE recycling does not depend on ATP-binding cassette transporter A1 activity.
      These studies provide initial evidence that impaired recycling of apoE4 could
      interfere with intracellular cholesterol transport and contribute to the
      pathophysiological lipoprotein profile observed in apoE4 homozygotes.

PMID- 15485882
TI  - Cooperation of the N-terminal Helicase and C-terminal endonuclease activities of
      Archaeal Hef protein in processing stalled replication forks.
AB  - Blockage of replication fork progression often occurs during DNA replication, and
      repairing and restarting stalled replication forks are essential events in all
      organisms for the maintenance of genome integrity. The repair system employs
      processing enzymes to restore the stalled fork. In Archaea Hef is a well
      conserved protein that specifically cleaves nicked, flapped, and fork-structured
      DNAs. This enzyme contains two distinct domains that are similar to the DEAH
      helicase family and XPF nuclease superfamily proteins. Analyses of truncated
      mutant proteins consisting of each domain revealed that the C-terminal nuclease
      domain independently recognized and incised fork-structured DNA. The N-terminal
      helicase domain also specifically unwound fork-structured DNA and Holliday
      junction DNA in the presence of ATP. Moreover, the endonuclease activity of the
      whole Hef protein was clearly stimulated by ATP hydrolysis catalyzed by the N
      terminal domain. These enzymatic properties suggest that Hef efficiently resolves
      stalled replication forks by two steps, which are branch point transfer to the 5'
      end of the nascent lagging strand by the N-terminal helicase followed by template
      strand incision for leading strand synthesis by the C-terminal endonuclease.

PMID- 15485883
TI  - Topology of the outer membrane usher PapC determined by site-directed
      fluorescence labeling.
AB  - In contrast to typical membrane proteins that span the lipid bilayer via
      transmembrane alpha-helices, bacterial outer membrane proteins adopt a beta
      barrel architecture composed of antiparallel transmembrane beta-strands. The
      topology of outer membrane proteins is difficult to predict accurately using
      computer algorithms, and topology mapping protocols commonly used for alpha
      helical membrane proteins do not work for beta-barrel proteins. We present here
      the topology of the PapC usher, an outer membrane protein required for assembly
      and secretion of P pili by the chaperone/usher pathway in uropathogenic
      Escherichia coli. An initial attempt to map PapC topology by insertion of
      protease cleavage sites was largely unsuccessful due to lack of cleavage at most
      sites and the requirement to disrupt the outer membrane to identify periplasmic
      sites. We therefore adapted a site-directed fluorescence labeling technique to
      permit topology mapping of outer membrane proteins using small molecule probes in
      intact bacteria. Using this method, we demonstrated that PapC has the potential
      to encode up to 32 transmembrane beta-strands. Based on experimental evidence, we
      propose that the usher consists of an N-terminal beta-barrel domain comprised of
      26 beta-strands and that a distinct C-terminal domain is not inserted into the
      membrane but is located instead within the lumen of the N-terminal beta-barrel
      similar to the plug domains encoded by the outer membrane iron-siderophore uptake
      proteins.

PMID- 15485884
TI  - Characterization of Azotobacter vinelandii nifZ deletion strains. Indication of
      stepwise MoFe protein assembly.
AB  - The nifZ gene product (NifZ) of Azotobacter vinelandii has been implicated in
      MoFe protein maturation. However, its exact function in this process remains
      largely unknown. Here, we report a detailed biochemical/biophysical
      characterization of His-tagged MoFe proteins purified from A. vinelandii nifZ and
      nifZ/nifB deletion strains DJ1182 and YM6A (Delta nifZ and Delta nifZ Delta nifB
      MoFe proteins, respectively). Our data from EPR, metal, activity, and stability
      analyses indicate that one alpha beta subunit pair of the Delta nifZ MoFe protein
      contains a P cluster ([8Fe-7S]) and an iron-molybdenum cofactor (FeMoco) ([Mo-7Fe
      9S-X-homocitrate]), whereas the other contains a presumed P cluster precursor,
      possibly comprising a pair of [4Fe-4S]-like clusters, and a vacant FeMoco site.
      Likewise, the Delta nifZ Delta nifB MoFe protein has the same composition as the
      Delta nifZ MoFe protein except for the absence of FeMoco, an effect caused by the
      deletion of the nifB gene. These results suggest that the MoFe protein is likely
      assembled stepwise, i.e. one alpha beta subunit pair of the tetrameric MoFe
      protein is assembled prior to the other, and that NifZ might act as a chaperone
      in the assembly of the second alpha beta subunit pair by facilitating a
      conformational rearrangement that is required for the formation of the P cluster
      through the condensation of two [4Fe-4S]-like clusters. The possibility of NifZ
      exercising its effect through the Fe protein was ruled out because the Fe
      proteins from nifZ and nifZ/nifB deletion strains are not defective in their
      normal functions. However, the detailed mechanism of how NifZ carries out its
      exact function in MoFe protein maturation awaits further investigation.

PMID- 15485885
TI  - Chemotaxis in Rhodobacter sphaeroides requires an atypical histidine protein
      kinase.
AB  - Rhodobacter sphaeroides has a complex chemosensory system comprising two classic
      CheAs, two atypical CheAs, and eight response regulators (six CheYs and two
      CheBs). The classic CheAs, CheA(1) and CheA(2), have similar domain structures to
      Escherichia coli CheA, whereas the atypical CheAs, CheA(3) and CheA(4), lack some
      of the domains found in E. coli CheA. CheA(2), CheA(3), and CheA(4) are all
      essential for chemotaxis. Here we demonstrate that CheA(3) and CheA(4) are both
      unable to undergo ATP-dependent autophosphorylation, however, CheA(4) is able to
      phosphorylate CheA(3). The in vitro kinetics of this phosphorylation reaction
      were consistent with a reaction mechanism in which CheA(3) associates with a
      CheA(4) dimer forming a complex, CheA(3)A(4). To the best of our knowledge,
      CheA(3)A(4) is the first characterized histidine protein kinase where the
      subunits are encoded by distinct genes. Selective phosphotransfer was observed
      from CheA(3)-P to the response regulators CheY(1), CheY(6), and CheB(2). Using
      phosphorylation site and kinase domain mutants of CheA we show that
      phosphosignaling involving CheA(2), CheA(3), and CheA(4) is essential for
      chemotaxis in R. sphaeroides. Interestingly, CheA(3) was not phosphorylated in
      vitro by CheA(1) or CheA(2), although CheA(1) and CheA(2) mutants with defective
      kinase domains were phosphorylated by CheA(4). Because in vivo CheA(3) and
      CheA(4) localize to the cytoplasmic chemotaxis cluster, while CheA(2) localizes
      to the polar chemotaxis cluster, it is likely that the physical separation of
      CheA(2) and CheA(4) prevents unwanted cross-talk between these CheAs.

PMID- 15485886
TI  - CD98hc (SLC3A2) interaction with beta 1 integrins is required for transformation.
AB  - CD98hc (SLC3A2) constitutively and specifically associates with beta(1) integrins
      and is highly expressed on the surface of human tumor cells irrespective of the
      tissue of origin. We have found here that expression of CD98hc promotes both
      anchorage- and serum-independent growth. This oncogenic activity is dependent on
      beta(1) integrin-mediated phosphoinositol 3-hydroxykinase stimulation and the
      level of surface expression of CD98hc. Using chimeras of CD98hc and the type II
      membrane protein CD69, we show that the transmembrane domain of CD98hc is
      necessary and sufficient for integrin association in cells. Furthermore,
      CD98hc/beta(1) integrin association is required for focal adhesion kinase
      dependent phosphoinositol 3-hydroxykinase activation and cellular transformation.
      Amino acids 82-87 in the putative cytoplasmic/transmembrane region appear to be
      critical for the oncogenic potential of CD98hc and provide a novel mechanism for
      tumor promotion by integrins. These results explain how high expression of CD98hc
      in human cancers contributes to transformation; furthermore, the transmembrane
      association of CD98hc and beta(1) integrins may provide a new target for cancer
      therapy.

PMID- 15485887
TI  - The serine/threonine kinase Akt Promotes Fc gamma receptor-mediated phagocytosis
      in murine macrophages through the activation of p70S6 kinase.
AB  - Fc gamma receptor (Fc gamma R) clustering by immune complexes activates multiple
      signaling pathways leading to phagocytosis. We and others have previously
      reported that Akt is phosphorylated in response to Fc gamma R clustering.
      However, the functional consequence of Akt activation by Fc gamma R is not known.
      Using Raw 264.7 macrophage cells transfected to overexpress either constitutively
      active myristoylated (Myr)-Akt or a dominant-negative CAAX-Akt and bone marrow
      macrophages (BMMs) from wild-type and transgenic mice expressing macrophage
      specific Myr-Akt, we analyzed the function of Akt in phagocytosis. We report that
      overexpression of Myr-Akt resulted in significant increase in phagocytic
      efficiency, whereas CAAX-Akt down-regulated phagocytosis in Raw 264.7 cells.
      Likewise BMMs expressing Myr-Akt displayed enhanced phagocytic ability. Analyzing
      the downstream effectors of Akt, we demonstrate that p70S6 kinase is
      constitutively phosphorylated in Myr-Akt-expressing BMMs. p70S6 kinase is
      reported to influence actin cytoskeleton and cell migration, suggesting that Akt
      may influence phagocytosis through the activation of p70S6 kinase. Consistent
      with this, overexpression of either wild-type or constitutively active but not a
      kinase-inactive p70S6 kinase in Raw 264.7 cells significantly enhanced
      phagocytosis. Likewise suppression of p70S6 kinase with rapamycin down-regulated
      phagocytic efficiency conferred by the expression of constitutively active Akt.
      These findings demonstrate a novel role for Akt in phagocytosis through the
      activation of p70S6 kinase.

PMID- 15485888
TI  - Tachykinin and tachykinin receptor of an ascidian, Ciona intestinalis:
      evolutionary origin of the vertebrate tachykinin family.
AB  - Tachykinins (TKs) are the most prevalent vertebrate brain/gut peptides. In this
      study, we originally identified authentic TKs and their receptor from a
      protochordate, Ciona intestinalis. The Ciona TK (Ci-TK) precursor, like mammalian
      gamma-preprotachykinin A (gamma-PPTA), encodes two TKs, Ci-TK-I and -II,
      including the -FXGLM-NH(2) vertebrate TK consensus. Mass spectrometry of the
      neural extract revealed the production of both Ci-TKs. Ci-TK-I contains several
      Substance P (SP)-typical amino acids, whereas a Thr is exceptionally located at
      position 4 from the C terminus of Ci-TK-II. The Ci-TK gene encodes both Ci-TKs in
      the same exon, indicating no alternative generation of Ci-TKs, unlike the PPTA
      gene. These results suggested that the alternative splicing of the PPTA gene was
      established during evolution of vertebrates. The only Ci-TK receptor, Ci-TK-R,
      was equivalently activated by Ci-TK-I, SP, and neurokinin A at physiological
      concentrations, whereas Ci-TK-II showed 100-fold less potent activity, indicating
      that the ligand selectivity of Ci-TK-R is distinct from those of vertebrate TK
      receptors. Ci-TK-I, like SP, also elicited the typical contraction on the guinea
      pig ileum. The Ci-TK gene was expressed in neurons of the brain ganglion, small
      cells in the intestine, and the zone 7 in the endostyle, which corresponds to the
      vertebrate thyroid gland. Furthermore, the Ci-TK-R mRNA was distributed in these
      three tissues plus the gonad. These results showed that Ci-TKs play major roles
      in sexual behavior and feeding in protochordates as brain/gut peptides and
      endocrine/paracrine molecules. Taken together, our data revealed the biochemical
      and structural origins of vertebrate TKs and their receptors.

PMID- 15485889
TI  - The glucocorticoid-induced gene tdag8 encodes a pro-apoptotic G protein-coupled
      receptor whose activation promotes glucocorticoid-induced apoptosis.
AB  - The apoptotic action of glucocorticoids on lymphocytes makes them effective
      therapeutics for many lymphoid malignancies. Although it is clear that
      glucocorticoid-induced apoptosis requires transcription, the gene products that
      induce apoptosis remain unknown. Using gene expression profiles of lymphoma cell
      lines and primary thymocytes treated with the synthetic glucocorticoid
      dexamethasone, we discovered that induction of tdag8 (T-cell death-associated
      gene 8) was a common event in each model system investigated. Activation of TDAG8
      by its agonist psychosine markedly enhanced dexamethasone-induced apoptosis in a
      TDAG8-dependent manner. Expression of a TDAG8-GFP fusion protein was sufficient
      to induce apoptosis, and repression of endogenous TDAG8 using RNA interference
      partially inhibited dexamethasone-induced apoptosis. Together, these data suggest
      that TDAG8 is a regulator of glucocorticoid-induced apoptosis and that agonists
      of TDAG8 may be promising agents to improve the efficacy of glucocorticoids for
      the treatment of leukemia and lymphoma.

PMID- 15485890
TI  - Interdomain tilt angle determines integrin-dependent function of the ninth and
      tenth FIII domains of human fibronectin.
AB  - Integrins are an important family of signaling receptors that mediate diverse
      cellular processes. The binding of the abundant extracellular matrix ligand
      fibronectin to integrins alpha(5)beta(1) and alpha(v)beta(3) is known to depend
      upon the Arg-Gly-Asp (RGD) motif on the tenth fibronectin FIII domain. The
      adjacent ninth FIII domain provides a synergistic effect on RGD-mediated integrin
      alpha(5)beta(1) binding and downstream function. The precise molecular basis of
      this synergy remains elusive. Here we have dissected further the function of
      FIII9 in integrin binding by analyzing the biological activity of the FIII9-10
      interdomain interface variants and by determining their structural and dynamic
      properties in solution. We demonstrate that the contribution of FIII9 to both
      alpha(5)beta(1) and alpha(v)beta(3) binding and downstream function critically
      depends upon the interdomain tilt between the FIII9 and FIII10 domains. Our data
      suggest that modulation of integrin binding by FIII9 may arise in part from its
      steric properties that determine accessibility of the RGD motif. These findings
      have wider implications for mechanisms of integrin-ligand binding in the
      physiological context.

PMID- 15485891
TI  - Chimeric G alpha i2/G alpha 13 proteins reveal the structural requirements for
      the binding and activation of the RGS-like (RGL)-containing Rho guanine
      nucleotide exchange factors (GEFs) by G alpha 13.
AB  - The alpha-subunit of G proteins of the G(12/13) family stimulate Rho by their
      direct binding to the RGS-like (RGL) domain of a family of Rho guanine nucleotide
      exchange factors (RGL-RhoGEFs) that includes PDZ-RhoGEF (PRG), p115RhoGEF, and
      LARG, thereby regulating cellular functions as diverse as shape and movement,
      gene expression, and normal and aberrant cell growth. The structural features
      determining the ability of G alpha(12/13) to bind RGL domains and the mechanism
      by which this association results in the activation of RGL-RhoGEFs are still
      poorly understood. Here, we explored the structural requirements for the
      functional interaction between G alpha(13) and RGL-RhoGEFs based on the structure
      of RGL domains and their similarity with the area by which RGS4 binds the switch
      region of G alpha(i) proteins. Using G alpha(i2), which does not bind RGL
      domains, as the backbone in which G alpha(13) sequences were swapped or mutated,
      we observed that the switch region of G alpha(13) is strictly necessary to bind
      PRG, and specific residues were identified that are critical for this
      association, likely by contributing to the binding surface. Surprisingly, the
      switch region of G alpha(13) was not sufficient to bind RGL domains, but instead
      most of its GTPase domain is required. Furthermore, membrane localization of G
      alpha(13) and chimeric G alpha(i2) proteins was also necessary for Rho
      activation. These findings revealed the structural features by which G alpha(13)
      interacts with RGL domains and suggest that molecular interactions occurring at
      the level of the plasma membrane are required for the functional activation of
      the RGL-containing family of RhoGEFs.

PMID- 15485892
TI  - Identification of a network involved in thapsigargin-induced apoptosis using a
      library of small interfering RNA expression vectors.
AB  - We describe here the construction of a library of small interfering RNA
      expression vectors targeted to a few hundred apoptosis-related genes and the
      application of this library to an investigation of thapsigargin (TG)-induced
      apoptosis. Thapsigargin triggers endoplasmic reticulum stress, with subsequent
      apoptosis, but the molecular mechanisms underlying this process are incompletely
      understood. Using our library, we identified three anti-apoptotic genes, namely,
      NOXA, E2F1, and MAPK1, in addition to already characterized genes in the
      apoptotic pathway. In contrast to proposals by others, our data revealed (i) that
      TG-induced apoptosis is associated with Apaf1 in a caspase-3- and caspase-9
      independent manner; (ii) that the E2F1-PUMA pathway might be involved; and (iii)
      that the ERK pathway, via MAP3K8 (mitogen-activated protein kinase kinase 8), is
      required for the induction by TG of apoptosis. Our study demonstrates clearly
      that unexpected and novel genes can be identified effectively by our method, and
      it provides evidence for the efficacy and utility of the comprehensive analysis
      of signaling networks and pathways using a library of small interfering RNA
      expression vectors.

PMID- 15485893
TI  - Identification of a region in the vitamin D-binding protein that mediates its C5a
      chemotactic cofactor function.
AB  - The vitamin D-binding protein (DBP), also known as group-specific component or Gc
      globulin, is a multifunctional plasma protein that can significantly enhance the
      leukocyte chemotactic activity to C5a and C5a des-Arg. DBP is a member of the
      albumin gene family and has a triple domain modular structure with extensive
      disulfide bonding that is characteristic of this protein family. The goal of this
      study was to identify a region in DBP that mediates the chemotactic cofactor
      function for C5a. Full-length and truncated versions of DBP (Gc-2 allele) were
      expressed in Escherichia coli using a glutathione S-transferase fusion protein
      expression system. The structure of the expressed proteins was confirmed by SDS
      PAGE and immunoblotting, whereas protein function was verified by quantitating
      the binding of [(3)H]vitamin D. Dibutyryl cAMP-differentiated HL-60 cells were
      utilized to test purified natural DBP and recombinant expressed DBP (reDBP) for
      their ability to enhance chemotaxis and intracellular Ca(2+) flux to C5a. Natural
      and full-length reDBP (458 amino acid residues) as well as truncated reDBPs that
      contained the N-terminal domain I (domains I and II, residues 1-378; domain I,
      residues 1-191) significantly enhanced both cell movement and intracellular
      Ca(2+) concentrations in response to C5a. Progressive truncation of DBP domain I
      localized the chemotactic enhancing region between residues 126-175. Overlapping
      peptides corresponding to this region were synthesized, and results indicate that
      a 20-amino-acid sequence (residues 130-149, 5'-EAFRKDPKEYANQFMWEYST-3') in domain
      I of DBP is essential for its C5a chemotactic cofactor function.

PMID- 15485894
TI  - Two major grapefruit juice components differ in time to onset of intestinal
      CYP3A4 inhibition.
AB  - Grapefruit juice elevates blood levels of some drugs taken orally, primarily by
      inhibiting intestinal CYP3A4-mediated first-pass metabolism. Two prominent
      furanocoumarins in the juice, 6',7'-dihydroxybergamottin (DHB) and bergamottin
      (BG), have been demonstrated as important contributors to grapefruit juice-drug
      interactions. Using CYP3A4-expressing Caco-2 cells and representative probes from
      distinct CYP3A4 substrate subgroups (midazolam, testosterone), we compared the
      time-dependent inhibitory properties of DHB and BG. DHB rapidly inhibited CYP3A4
      activity in a substrate-independent fashion with maximal inhibition (>/=85%)
      generally occurring within 30 min. In contrast, BG had a slower onset and
      exhibited substrate-dependent inhibition. Whereas testosterone 6beta
      hydroxylation was inhibited by >50% with all exposure times (0.5-3 h), midazolam
      1'-hydroxylation was unaffected, or even activated, with short exposure times (<1
      h). After a 3-h exposure, however, BG had begun to "catch up" with DHB, causing
      >/=70% inhibition, independent of substrate. Likewise, loss of CYP3A4 protein,
      believed to reflect rapid intracellular degradation of the enzyme following
      mechanism-based inactivation, was comparable between the furanocoumarins (40
      50%). The time course of BG-mediated inhibition was similar after just a 30-min
      exposure, indicating that the short exposure presumed to occur after juice
      ingestion is sufficient to initiate the events required to cause substantial
      inhibition (>/=50%). These results suggest that after ingestion of a glass of
      grapefruit juice, CYP3A4 is maximally inhibited by DHB before BG has the
      opportunity to act. However, foods containing BG but not DHB (e.g., lime juice)
      could produce a substrate-dependent interaction with drugs consumed
      concomitantly, but a substrate-independent interaction with drugs taken several
      hours after food consumption.

PMID- 15485895
TI  - Design, synthesis, and analysis of a polyethelene glycol-modified (PEGylated)
      small molecule inhibitor of integrin {alpha}4{beta}1 with improved pharmaceutical
      properties.
AB  - Integrin alpha4beta1 plays an important role in inflammatory processes by
      regulating the migration of leukocytes into inflamed tissues. Previously, we
      identified BIO5192 [2(S)-{[1-(3,5-dichloro-benzenesulfonyl)-pyrrolidine-2(S)
      carbonyl]-amino}-4-[4-methyl-2(S)-(methyl-{2-[4-(3-o-tolyl-ureido)-phenyl]
      acetyl}-amino)-pentanoylamino]-butyric acid], a highly selective and potent (K(D)
      of 9 pM) small molecule inhibitor of alpha4beta1. Although BIO5192 is efficacious
      in various animal models of inflammatory disease, high doses and daily treatment
      of the compound are needed to achieve a therapeutic effect because of its
      relatively short serum half-life. To address this issue, polyethylene glycol
      modification (PEGylation) was used as an approach to improve systemic exposure.
      BIO5192 was PEGylated by a targeted approach in which derivatizable amino groups
      were incorporated into the molecule. Two sites were identified that could be
      modified, and from these, five PEGylated compounds were synthesized and
      characterized. One compound, 2a-PEG (K(D) of 19 pM), was selected for in vivo
      studies. The pharmacokinetic and pharmacodynamic properties of 2a-PEG were
      dramatically improved relative to the unmodified compound. The PEGylated compound
      was efficacious in a rat model of experimental autoimmune encephalomyelitis at a
      30-fold lower molar dose than the parent compound and required only a once-a-week
      dosing regimen compared with a daily treatment for BIO5192. Compound 2a-PEG was
      highly selective for alpha4beta1. These studies demonstrate the feasibility of
      PEGylation of alpha4beta1-targeted small molecules with retention of activity in
      vitro and in vivo. 2a-PEG, and related compounds, will be valuable reagents for
      assessing alpha4beta1 biology and may provide a new therapeutic approach to
      treatment of human inflammatory diseases.

PMID- 15485896
TI  - Notch subunit heterodimerization and prevention of ligand-independent proteolytic
      activation depend, respectively, on a novel domain and the LNR repeats.
AB  - Notch proteins are transmembrane receptors that participate in a highly conserved
      signaling pathway that regulates morphogenesis in metazoans. Newly synthesized
      Notch receptors are proteolytically cleaved during transit to the cell surface,
      creating heterodimeric mature receptors comprising noncovalently associated
      extracellular (N(EC)) and transmembrane (N) subunits. Ligand binding activates
      Notch by inducing two successive proteolytic cleavages, catalyzed by
      metalloproteases and gamma-secretase, respectively, that permit the intracellular
      portion of N to translocate to the nucleus and activate transcription of target
      genes. Prior work has shown that the presence of N(EC) prevents ligand
      independent activation of N, but the mechanisms involved are poorly understood.
      Here, we define the roles of two regions at the C-terminal end of N(EC) that
      participate in maintaining the integrity of resting Notch receptors through
      distinct mechanisms. The first region, a hydrophobic, previously uncharacterized
      portion of N(EC), is sufficient to form stable complexes with the extracellular
      portion of N. The second region, consisting of the three Lin12/Notch repeats, is
      not needed for heterodimerization but acts to protect N from ligand-independent
      cleavage by metalloproteases. Together, these two contiguous regions of N(EC)
      impose crucial restraints that prevent premature Notch receptor activation.

PMID- 15485897
TI  - FF domains of CA150 bind transcription and splicing factors through multiple weak
      interactions.
AB  - The human transcription factor CA150 modulates human immunodeficiency virus type
      1 gene transcription and contains numerous signaling elements, including six FF
      domains. Repeated FF domains are present in several transcription and splicing
      factors and can recognize phosphoserine motifs in the C-terminal domain (CTD) of
      RNA polymerase II (RNAPII). Using mass spectrometry, we identify a number of
      nuclear binding partners for the CA150 FF domains and demonstrate a direct
      interaction between CA150 and Tat-SF1, a protein involved in the coupling of
      splicing and transcription. CA150 FF domains recognize multiple sites within the
      Tat-SF1 protein conforming to the consensus motif (D/E)(2/5)-F/W/Y-(D/E)(2/5).
      Individual FF domains are capable of interacting with Tat-SF1 peptide ligands in
      an equivalent and noncooperative manner, with affinities ranging from 150 to 500
      microM. Repeated FF domains therefore appear to bind their targets through
      multiple weak interactions with motifs comprised of negatively charged residues
      flanking aromatic amino acids. The RNAPII CTD represents a consensus FF domain
      binding site, contingent on generation of the requisite negative charges by
      phosphorylation of serines 2 and 5. We propose that CA150, through the dual
      recognition of acidic motifs in proteins such as Tat-SF1 and the phosphorylated
      CTD, could mediate the recruitment of transcription and splicing factors to
      actively transcribing RNAPII.

PMID- 15485898
TI  - Human immunodeficiency virus type 1 Vpr-mediated G2 arrest requires Rad17 and
      Hus1 and induces nuclear BRCA1 and gamma-H2AX focus formation.
AB  - Eukaryotic cells have evolved a complex mechanism for sensing DNA damage during
      genome replication. Activation of this pathway prevents entry into mitosis to
      allow for either DNA repair or, in the event of irreparable damage, commitment to
      apoptosis. Under conditions of replication stress, the damage signal is initiated
      by the ataxia-telangiectasia-mutated and Rad3-related kinase ATR. We recently
      demonstrated that the human immunodeficiency virus type 1 (HIV-1) gene product
      viral protein R (Vpr) arrests infected cells in the G(2) phase via the activation
      of ATR. In the present study, we show that the activation of ATR by Vpr is
      analogous to activation by certain genotoxic agents, both mechanistically and in
      its downstream consequences. Specifically, we show a requirement for Rad17 and
      Hus1 to induce G(2) arrest as well as Vpr-induced phosphorylation of histone 2A
      variant X (H2AX) and formation of nuclear foci containing H2AX and breast cancer
      susceptibility protein 1. These results demonstrate that G(2) arrest mediated by
      the HIV-1 gene product Vpr utilizes the cellular signaling pathway whose
      physiological function is to recognize replication stress. These findings should
      contribute to a greater understanding of how HIV-1 manipulates the CD4(+)
      lymphocyte cell cycle and apoptosis induction in the progressive CD4(+)
      lymphocyte depletion characteristic of HIV-1 pathogenesis.

PMID- 15485899
TI  - Conditional activation of akt in adult skeletal muscle induces rapid hypertrophy.
AB  - Skeletal muscle atrophy is a severe morbidity caused by a variety of conditions,
      including cachexia, cancer, AIDS, prolonged bedrest, and diabetes. One strategy
      in the treatment of atrophy is to induce the pathways normally leading to
      skeletal muscle hypertrophy. The pathways that are sufficient to induce
      hypertrophy in skeletal muscle have been the subject of some controversy. We
      describe here the use of a novel method to produce a transgenic mouse in which a
      constitutively active form of Akt can be inducibly expressed in adult skeletal
      muscle and thereby demonstrate that acute activation of Akt is sufficient to
      induce rapid and significant skeletal muscle hypertrophy in vivo, accompanied by
      activation of the downstream Akt/p70S6 kinase protein synthesis pathway. Upon
      induction of Akt in skeletal muscle, there was also a significant decrease in
      adipose tissue. These findings suggest that pharmacologic approaches directed
      toward activating Akt will be useful in inducing skeletal muscle hypertrophy and
      that an increase in lean muscle mass is sufficient to decrease fat storage.

PMID- 15485900
TI  - Genetic steps of mammalian homologous repair with distinct mutagenic
      consequences.
AB  - Repair of chromosomal breaks is essential for cellular viability, but misrepair
      generates mutations and gross chromosomal rearrangements. We investigated the
      interrelationship between two homologous-repair pathways, i.e., mutagenic single
      strand annealing (SSA) and precise homology-directed repair (HDR). For this, we
      analyzed the efficiency of repair in mammalian cells in which double-strand break
      (DSB) repair components were disrupted. We observed an inverse relationship
      between HDR and SSA when RAD51 or BRCA2 was impaired, i.e., HDR was reduced but
      SSA was increased. In particular, expression of an ATP-binding mutant of RAD51
      led to a >90-fold shift to mutagenic SSA repair. Additionally, we found that
      expression of an ATP hydrolysis mutant of RAD51 resulted in more extensive gene
      conversion, which increases genetic loss during HDR. Disruption of two other DSB
      repair components affected both SSA and HDR, but in opposite directions: SSA and
      HDR were reduced by mutation of Brca1, which, like Brca2, predisposes to breast
      cancer, whereas SSA and HDR were increased by Ku70 mutation, which affects
      nonhomologous end joining. Disruption of the BRCA1-associated protein BARD1 had
      effects similar to those of mutation of BRCA1. Thus, BRCA1/BARD1 has a role in
      homologous repair before the branch point of HDR and SSA. Interestingly, we found
      that Ku70 mutation partially suppresses the homologous-repair defects of BARD1
      disruption. We also examined the role of RAD52 in homologous repair. In contrast
      to yeast, Rad52(-)(/)(-) mouse cells had no detectable HDR defect, although SSA
      was decreased. These results imply that the proper genetic interplay of repair
      factors is essential to limit the mutagenic potential of DSB repair.

PMID- 15485901
TI  - Tumor necrosis factor alpha induction of NF-kappaB requires the novel coactivator
      SIMPL.
AB  - A myriad of stimuli including proinflammatory cytokines, viruses, and chemical
      and mechanical insults activate a kinase complex composed of IkappaB kinase beta
      (IKK-beta), IKK-alpha, and IKK-gamma/N, leading to changes in NF-kappaB-dependent
      gene expression. However, it is not clear how the NF-kappaB response is tailored
      to specific cellular insults. Signaling molecule that interacts with mouse pelle
      like kinase (SIMPL) is a signaling component required for tumor necrosis factor
      alpha (TNF-alpha)-dependent but not interleukin-1-dependent NF-kappaB activation.
      Herein we demonstrate that nuclear localization of SIMPL is required for type I
      TNF receptor-induced NF-kappaB activity. SIMPL interacts with nuclear p65 in a
      TNF-alpha-dependent manner to promote endogenous NF-kappaB-dependent gene
      expression. The interaction between SIMPL and p65 enhances p65 transactivation
      activity. These data support a model in which TNF-alpha activation of NF-kappaB
      dependent-gene expression requires nuclear relocalization of p65 as well as
      nuclear relocalization of SIMPL, generating a TNF-alpha-specific induction of
      gene expression.

PMID- 15485902
TI  - ARF impedes NPM/B23 shuttling in an Mdm2-sensitive tumor suppressor pathway.
AB  - The ARF tumor suppressor is widely regarded as an upstream activator of p53
      dependent growth arrest and apoptosis. However, recent findings indicate that ARF
      can also regulate the cell cycle in the absence of p53. In search of p53
      independent ARF targets, we isolated nucleophosmin (NPM/B23), a protein we show
      is required for proliferation, as a novel ARF binding protein. In response to
      hyperproliferative signals, ARF is upregulated, resulting in the nucleolar
      retention of NPM and concomitant cell cycle arrest. The Mdm2 oncogene outcompetes
      NPM/B23 for ARF binding, and introduction of Mdm2 reverses ARF's p53-independent
      properties: in vitro, NPM is released from ARF-containing protein complexes, and
      in vivo S phase progression ensues. ARF induction by oncogenes or replicative
      senescence does not alter NPM/B23 protein levels but rather prevents its
      nucleocytoplasmic shuttling without inhibiting rRNA processing. By actively
      sequestering NPM in the nucleolus, ARF utilizes an additional mechanism of tumor
      suppression, one that is readily antagonized by Mdm2.

PMID- 15485903
TI  - BRUCE, a giant E2/E3 ubiquitin ligase and inhibitor of apoptosis protein of the
      trans-Golgi network, is required for normal placenta development and mouse
      survival.
AB  - BRUCE is a highly conserved 528-kDa peripheral membrane protein of the trans
      Golgi network. Owing to the presence of an N-terminal single baculovirus
      inhibitor repeat, BRUCE functions as an inhibitor of apoptosis protein and blocks
      apoptosis when overexpressed. In addition, due to the presence of a C-terminal
      ubiquitin-conjugating domain, BRUCE can covalently attach ubiquitin to
      substrates. Here we report the generation and characterization of BRUCE-deficient
      mice. Complete inactivation of the BRUCE gene resulted in perinatal lethality and
      growth retardation discernible after embryonic day 14. The growth defect is
      linked to impaired placental development and may be caused by insufficient oxygen
      and nutrient transfer across the placenta. Chorioallantoic placentation initiated
      normally, but the mutant placenta showed an impaired maturation of the labyrinth
      layer and a significant reduction of the spongiotrophoblast. No evidence for an
      elevated apoptosis rate was detectable in embryonic and extraembryonic tissues
      and in knockout fibroblasts. Thus, although BRUCE is broadly expressed in
      embryonic, extraembryonic, and adult mouse tissues, this bifunctional protein
      might play a unique role in normal trophoblast differentiation and embryonic
      survival.

PMID- 15485904
TI  - The human c-Fes tyrosine kinase binds tubulin and microtubules through separate
      domains and promotes microtubule assembly.
AB  - The c-Fes protein-tyrosine kinase (Fes) has been implicated in the
      differentiation of vascular endothelial, myeloid hematopoietic, and neuronal
      cells, promoting substantial morphological changes in these cell types. The
      mechanism by which Fes promotes morphological aspects of cellular differentiation
      is unknown. Using COS-7 cells as a model system, we observed that Fes strongly
      colocalizes with microtubules in vivo when activated via coiled-coil mutation or
      by coexpression with an active Src family kinase. In contrast, wild-type Fes
      showed a diffuse cytoplasmic localization in this system, which correlated with
      undetectable kinase activity. Coimmunoprecipitation and immunofluorescence
      microscopy showed that the N-terminal Fes/CIP4 homology (FCH) domain is involved
      in Fes interaction with soluble unpolymerized tubulin. However, the FCH domain
      was not required for colocalization with polymerized microtubules in vivo. In
      contrast, a functional SH2 domain was essential for microtubule localization of
      Fes, consistent with the strong tyrosine phosphorylation of purified tubulin by
      Fes in vitro. Using a microtubule nucleation assay, we observed that purified c
      Fes also catalyzed extensive tubulin polymerization in vitro. Taken together,
      these results identify c-Fes as a regulator of the tubulin cytoskeleton that may
      contribute to Fes-induced morphological changes in myeloid hematopoietic and
      neuronal cells.

PMID- 15485905
TI  - Generic features of tertiary chromatin structure as detected in natural
      chromosomes.
AB  - Knowledge of tertiary chromatin structure in mammalian interphase chromosomes is
      largely derived from artificial tandem arrays. In these model systems, light
      microscope images reveal fibers or beaded fibers after high-density targeting of
      transactivators to insertional domains spanning several megabases. These images
      of fibers have lent support to chromonema fiber models of tertiary structure. To
      assess the relevance of these studies to natural mammalian chromatin, we
      identified two different approximately 400-kb regions on human chromosomes 6 and
      22 and then examined light microscope images of interphase tertiary chromatin
      structure when the regions were transcriptionally active and inactive. When
      transcriptionally active, these natural chromosomal regions elongated, yielding
      images characterized by a series of adjacent puncta or "beads", referred to
      hereafter as beaded images. These elongated structures required transcription for
      their maintenance. Thus, despite marked differences in the density and the mode
      of transactivation, the natural and artificial systems showed similarities,
      suggesting that beaded images are generic features of transcriptionally active
      tertiary chromatin. We show here, however, that these images do not necessarily
      favor chromonema fiber models but can also be explained by a radial-loop model or
      even a simple nucleosome affinity, random-chain model. Thus, light microscope
      images of tertiary structure cannot distinguish among competing models, although
      they do impose key constraints: chromatin must be clustered to yield beaded
      images and then packaged within each cluster to enable decondensation into
      adjacent clusters.

PMID- 15485906
TI  - Cofilin 1 is revealed as an inhibitor of glucocorticoid receptor by analysis of
      hormone-resistant cells.
AB  - Significant knowledge about glucocorticoid signaling has accumulated, yet many
      aspects remain unknown. We aimed to discover novel factors involved in
      glucocorticoid receptor regulation that do not necessarily require direct
      receptor interaction. We achieved this by using a functional genetic screen: a
      stable cell line which cannot survive hormone treatment was engineered, randomly
      mutated, and selected in the presence of glucocorticoid. A hormone-resistant
      clone was analyzed by two-dimensional gel electrophoresis. Differentially
      expressed proteins were identified and tested as candidates for regulation of the
      glucocorticoid receptor. An unexpected candidate, cofilin 1, inhibited receptor
      activity. Cofilin is known to promote actin depolymerization and filament
      severing. Several experiments suggest that this feature of cofilin is involved in
      its inhibitory action. Both its actin depolymerization activity and its
      inhibitory action on the receptor are dependent on its phosphorylation state.
      Treatment of cells with a cytoskeleton-disrupting agent decreased receptor
      activity, as did overexpression of actin, particularly a mutant actin that does
      not polymerize. In addition, overexpression of cofilin and actin as well as
      chemical cytoskeleton disruption changed the subcellular receptor distribution
      and upregulated c-Jun, which could constitute the inhibitory mechanism of
      cofilin. In summary, cofilin represents a novel factor that can cause
      glucocorticoid resistance.

PMID- 15485907
TI  - ALK7, a receptor for nodal, is dispensable for embryogenesis and left-right
      patterning in the mouse.
AB  - Mesendoderm formation and left-right patterning during vertebrate development
      depend upon selected members of the transforming growth factor beta superfamily,
      particularly Nodal and Nodal-related ligands. Two type I serine/threonine kinase
      receptors have been identified for Nodal, ALK4 and ALK7. Mouse embryos lacking
      ALK4 fail to produce mesendoderm and die shortly after gastrulation, resembling
      the phenotype of Nodal knockout mice. Whether ALK4 contributes to left-right
      patterning is still unknown. Here we report the generation and initial
      characterization of mice lacking ALK7. Homozygous mutant mice were born at the
      expected frequency and remained viable and fertile. Viability at weaning was not
      different from that of the wild type in ALK7(-/-); Nodal(+/-) and ALK7(-/-);
      ALK4(+/-) compound mutants. ALK7 and ALK4 were highly expressed in interdigital
      regions of the developing limb bud. However, ALK7 mutant mice displayed no
      skeletal abnormalities or limb malformations. None of the left-right patterning
      abnormalities and organogenesis defects identified in mice carrying mutations in
      Nodal or in genes encoding ActRIIA and ActRIIB coreceptors, including heart
      malformations, pulmonary isomerism, right-sided gut, and spleen hypoplasia, were
      observed in mice lacking ALK7. Finally, the histological organization of the
      cerebellum, cortex, and hippocampus, all sites of significant ALK7 expression in
      the rodent brain, appeared normal in ALK7 mutant mice. We conclude that ALK7 is
      not an essential mediator of Nodal signaling during mesendoderm formation and
      left-right patterning in the mouse but may instead mediate other activities of
      Nodal and related ligands in the development or function of particular tissues
      and organs.

PMID- 15485908
TI  - Central role of the threonine residue within the p+1 loop of receptor tyrosine
      kinase in STAT3 constitutive phosphorylation in metastatic cancer cells.
AB  - The receptor tyrosine kinases (RTKs) RET, MET, and RON all carry the Met(p+1loop)
      ->Thr point mutation (i.e., 2B mutation), leading to the formation of tumors with
      high metastatic potential. Utilizing a novel antibody array, we identified
      constitutive phosphorylation of STAT3 in cells expressing the 2B mutation but not
      wild-type RET. MET or RON with the 2B mutation also constitutively phosphorylated
      STAT3. Members of the EPH, the only group of wild-type RTK that carry
      Thr(p+1loop) residue, are often expressed unexpectedly in different types of
      cancers. Ectopic expression of wild-type but not Thr(p+1loop)-->Met substituted
      EPH family members constitutively phosphorylated STAT3. In both RTK(Metp+1loop)
      with 2B mutation and wild-type EPH members the Thr(p+1loop) residue is required
      for constitutive kinase autophosphorylation and STAT3 recruitment. In multiple
      endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nuclear
      enrichment of STAT3 and elevated expression of CXCR4 was detected in metastatic
      thyroid C-cell carcinoma in the liver. In breast adenocarcinoma cell lines
      expressing multiple EPH members, STAT3 constitutively bound to the promoters of
      MUC1, MUC4, and MUC5B genes. Inhibiting STAT3 expression resulted in reduced
      expression of these metastasis-related genes and inhibited mobility. These
      findings provide insight into Thr(p+1loop) residue in RTK autophosphorylation and
      constitutive activation of STAT3 in metastatic cancer cells.

PMID- 15485909
TI  - Rad62 protein functionally and physically associates with the smc5/smc6 protein
      complex and is required for chromosome integrity and recombination repair in
      fission yeast.
AB  - Smc5 and Smc6 proteins form a heterodimeric SMC (structural maintenance of
      chromosome) protein complex like SMC1-SMC3 cohesin and SMC2-SMC4 condensin, and
      they associate with non-SMC proteins Nse1 and Nse2 stably and Rad60 transiently.
      This multiprotein complex plays an essential role in maintaining chromosome
      integrity and repairing DNA double strand breaks (DSBs). This study characterizes
      a Schizosaccharomyces pombe mutant rad62-1, which is hypersensitive to methyl
      methanesulfonate (MMS) and synthetically lethal with rad2 (a feature of
      recombination mutants). rad62-1 is hypersensitive to UV and gamma rays, epistatic
      with rhp51, and defective in repair of DSBs. rad62 is essential for viability and
      genetically interacts with rad60, smc6, and brc1. Rad62 protein physically
      associates with the Smc5-6 complex. rad62-1 is synthetically lethal with
      mutations in the genes promoting recovery from stalled replication, such as rqh1,
      srs2, and mus81, and those involved in nucleotide excision repair like rad13 and
      rad16. These results suggest that Rad62, like Rad60, in conjunction with the Smc5
      6 complex, plays an essential role in maintaining chromosome integrity and
      recovery from stalled replication by recombination.

PMID- 15485910
TI  - Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart
      development, and heart function.
AB  - Oxygen radicals regulate many physiological processes, such as signaling,
      proliferation, and apoptosis, and thus play a pivotal role in pathophysiology and
      disease development. There are at least two thioredoxin
      reductase/thioredoxin/peroxiredoxin systems participating in the cellular defense
      against oxygen radicals. At present, relatively little is known about the
      contribution of individual enzymes to the redox metabolism in different cell
      types. To begin to address this question, we generated and characterized mice
      lacking functional mitochondrial thioredoxin reductase (TrxR2). Ubiquitous Cre
      mediated inactivation of TrxR2 is associated with embryonic death at embryonic
      day 13. TrxR2(TrxR2(-/-)minus;/TrxR2(-/-)minus;) embryos are smaller and severely
      anemic and show increased apoptosis in the liver. The size of hematopoietic
      colonies cultured ex vivo is dramatically reduced. TrxR2-deficient embryonic
      fibroblasts are highly sensitive to endogenous oxygen radicals when glutathione
      synthesis is inhibited. Besides the defect in hematopoiesis, the ventricular
      heart wall of TrxR2(TrxR2(-/-)minus;/TrxR2(-/-)minus;) embryos is thinned and
      proliferation of cardiomyocytes is decreased. Cardiac tissue-restricted ablation
      of TrxR2 results in fatal dilated cardiomyopathy, a condition reminiscent of that
      in Keshan disease and Friedreich's ataxia. We conclude that TrxR2 plays a pivotal
      role in both hematopoiesis and heart function.

PMID- 15485912
TI  - Interactions of eukaryotic translation initiation factor 3 (eIF3) subunit NIP1/c
      with eIF1 and eIF5 promote preinitiation complex assembly and regulate start
      codon selection.
AB  - The N-terminal domain (NTD) of NIP1/eIF3c interacts directly with eIF1 and eIF5
      and indirectly through eIF5 with the eIF2-GTP-Met-tRNA(i)(Met) ternary complex
      (TC) to form the multifactor complex (MFC). We investigated the physiological
      importance of these interactions by mutating 16 segments spanning the NIP1-NTD.
      Mutations in multiple segments reduced the binding of eIF1 or eIF5 to the NIP1
      NTD. Mutating a C-terminal segment of the NIP1-NTD increased utilization of UUG
      start codons (Sui(-) phenotype) and was lethal in cells expressing eIF5-G31R that
      is hyperactive in stimulating GTP hydrolysis by the TC at AUG codons. Both
      effects of this NIP1 mutation were suppressed by eIF1 overexpression, as was the
      Sui(-) phenotype conferred by eIF5-G31R. Mutations in two N-terminal segments of
      the NIP1-NTD suppressed the Sui(-) phenotypes produced by the eIF1-D83G and eIF5
      G31R mutations. From these and other findings, we propose that the NIP1-NTD
      coordinates an interaction between eIF1 and eIF5 that inhibits GTP hydrolysis at
      non-AUG codons. Two NIP1-NTD mutations were found to derepress GCN4 translation
      in a manner suppressed by overexpressing the TC, indicating that MFC formation
      stimulates TC recruitment to 40S ribosomes. Thus, the NIP1-NTD is required for
      efficient assembly of preinitiation complexes and also regulates the selection of
      AUG start codons in vivo.

PMID- 15485911
TI  - The Yaf9 component of the SWR1 and NuA4 complexes is required for proper gene
      expression, histone H4 acetylation, and Htz1 replacement near telomeres.
AB  - Yaf9, Taf14, and Sas5 comprise the YEATS domain family in Saccharomyces
      cerevisiae, which in humans includes proteins involved in acute leukemias. The
      YEATS domain family is essential, as a yaf9Delta taf14Delta sas5Delta triple
      mutant is nonviable. We verify that Yaf9 is a stable component of NuA4, an
      essential histone H4 acetyltransferase complex. Yaf9 is also associated with the
      SWR1 complex, which deposits the histone H2A variant Htz1. However, the
      functional contribution of Yaf9 to these complexes has not been determined.
      Strains lacking YAF9 are sensitive to DNA-damaging agents, cold, and caffeine,
      and the YEATS domain is required for full Yaf9 function. NuA4 lacking Yaf9
      retains histone acetyltransferase activity in vitro, and Yaf9 does not markedly
      reduce bulk H4 acetylation levels, suggesting a role for Yaf9 in the targeting or
      regulation of NuA4. Interestingly, yaf9Delta strains display reduced
      transcription of genes near certain telomeres, and their repression is correlated
      with reduced H4 acetylation, reduced occupancy by Htz1, and increased occupancy
      by the silencing protein Sir3. Additionally, the spectra of phenotypes, genes,
      and telomeres affected in yaf9Delta and htz1Delta strains are significantly
      similar, further supporting a role for Yaf9 in Htz1 deposition. Taken together,
      these data indicate that Yaf9 may function in NuA4 and SWR1 complexes to help
      antagonize silencing near telomeres.

PMID- 15485913
TI  - Characterization of stanniocalcin 2, a novel target of the mammalian unfolded
      protein response with cytoprotective properties.
AB  - Accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces a
      highly conserved homeostatic response in all eukaryotic cells, termed the
      unfolded-protein response (UPR). Here we describe the characterization of
      stanniocalcin 2 (STC2), a mammalian homologue of a calcium- and phosphate
      regulating hormone first identified in fish, as a novel target of the UPR.
      Expression of STC2 gene is rapidly upregulated in cultured cells after exposure
      to tunicamycin and thapsigargin, by ATF4 after activation of the ER-resident
      kinase PERK. In addition, STC2 expression is also activated in neuronal cells by
      oxidative stress and hypoxia but not by several cellular stresses unrelated to
      the UPR. In contrast, expression of another homologue, STC1, is only upregulated
      by hypoxia independent of PERK or ATF4 expression. In vivo studies revealed that
      rat cortical neurons rapidly upregulate STC2 after transient middle cerebral
      artery occlusion. Finally, siRNA-mediated inhibition of STC2 expression renders
      N2a neuroblastoma cells and HeLa cells significantly more vulnerable to apoptotic
      cell death after treatment with thapsigargin, and overexpression of STC2
      attenuated thapsigargin-induced cell death. Consequently, induced STC2 expression
      is an essential feature of survival component of the UPR.

PMID- 15485914
TI  - p53 Deficiency rescues neuronal apoptosis but not differentiation in DNA
      polymerase beta-deficient mice.
AB  - In mammalian cells, DNA polymerase beta (Polbeta) functions in base excision
      repair. We have previously shown that Polbeta-deficient mice exhibit extensive
      neuronal cell death (apoptosis) in the developing nervous system and that the
      mice die immediately after birth. Here, we studied potential roles in the
      phenotype for p53, which has been implicated in DNA damage sensing, cell cycle
      arrest, and apoptosis. We generated Polbeta(-/-) p53(-/-) double-mutant mice and
      found that p53 deficiency dramatically rescued neuronal apoptosis associated with
      Polbeta deficiency, indicating that p53 mediates the apoptotic process in the
      nervous system. Importantly, proliferation and early differentiation of neuronal
      progenitors in Polbeta(-/-) p53(-/-) mice appeared normal, but their brains
      obviously displayed cytoarchitectural abnormalities; moreover, the mice, like
      Polbeta(-/-) p53(+/+) mice, failed to survive after birth. Thus, we strongly
      suggest a crucial role for Polbeta in the differentiation of specific neuronal
      cell types.

PMID- 15485915
TI  - DNA damage-induced cell cycle checkpoint control requires CtIP, a phosphorylation
      dependent binding partner of BRCA1 C-terminal domains.
AB  - The BRCA1 C-terminal (BRCT) domain has recently been implicated as a phospho
      protein binding domain. We demonstrate here that a CTBP-interacting protein CtIP
      interacts with BRCA1 BRCT domains in a phosphorylation-dependent manner. The
      CtIP/BRCA1 complex only exists in G(2) phase and is required for DNA damage
      induced Chk1 phosphorylation and the G(2)/M transition checkpoint. However, the
      CtIP/BRCA1 complex is not required for the damage-induced G(2) accumulation
      checkpoint, which is controlled by a separate BRCA1/BACH1 complex. Taken
      together, these data not only implicate CtIP as a critical player in cell cycle
      checkpoint control but also provide molecular mechanisms by which BRCA1 controls
      multiple cell cycle transitions after DNA damage.

PMID- 15485916
TI  - Identification of the proteins required for biosynthesis of diphthamide, the
      target of bacterial ADP-ribosylating toxins on translation elongation factor 2.
AB  - Diphthamide, a posttranslational modification of translation elongation factor 2
      that is conserved in all eukaryotes and archaebacteria and is the target of
      diphtheria toxin, is formed in yeast by the actions of five proteins, Dph1 to -5,
      and a still unidentified amidating enzyme. Dph2 and Dph5 were previously
      identified. Here, we report the identification of the remaining three yeast
      proteins (Dph1, -3, and -4) and show that all five Dph proteins have either
      functional (Dph1, -2, -3, and -5) or sequence (Dph4) homologs in mammals. We
      propose a unified nomenclature for these proteins (e.g., HsDph1 to -5 for the
      human proteins) and their genes based on the yeast nomenclature. We show that
      Dph1 and Dph2 are homologous in sequence but functionally independent. The human
      tumor suppressor gene OVCA1, previously identified as homologous to yeast DPH2,
      is shown to actually be HsDPH1. We show that HsDPH3 is the previously described
      human diphtheria toxin and Pseudomonas exotoxin A sensitivity required gene 1 and
      that DPH4 encodes a CSL zinc finger-containing DnaJ-like protein. Other features
      of these genes are also discussed. The physiological function of diphthamide and
      the basis of its ubiquity remain a mystery, but evidence is presented that Dph1
      to -3 function in vivo as a protein complex in multiple cellular processes.

PMID- 15485917
TI  - Uterus hyperplasia and increased carcinogen-induced tumorigenesis in mice
      carrying a targeted mutation of the Chk2 phosphorylation site in Brca1.
AB  - The tumor suppressor BRCA1 contains multiple functional domains that interact
      with many proteins. After DNA damage, BRCA1 is phosphorylated by CHK2 at serine
      988, followed by a change in its intracellular location. To study the functions
      of CHK2-dependent phosphorylation of BRCA1, we generated a mouse model carrying
      the mutation S971A (S971 in mouse Brca1 corresponds to S988 in human BRCA1) by
      gene targeting. Brca1(S971A/S971A) mice were born at the expected ratio without a
      developmental defect, unlike previously reported Brca1 mutant mice. However,
      Brca1(S971A/S971A) mice suffered a moderately increased risk of spontaneous tumor
      formation, with a majority of females developing uterus hyperplasia and ovarian
      abnormalities by 2 years of age. After treatment with DNA-damaging agents,
      Brca1(S971A/S971A) mice exhibited several abnormalities, including increased body
      weight, abnormal hair growth pattern, lymphoma, mammary tumors, and endometrial
      tumors. In addition, the onset of tumor formation became accelerated, and 80% of
      the mutant mice had developed tumors by 1 year of age. We demonstrated that the
      Brca1(S971A/S971A) cells displayed reduced ability to activate the G(2)/M cell
      cycle checkpoint upon gamma-irradiation and to stabilize p53 following N-methyl
      N'-nitro-N-nitrosoguanidine treatment. These observations suggest that Chk2
      phosphorylation of S971 is involved in Brca1 function in modulating the DNA
      damage response and repressing tumor formation.

PMID- 15485918
TI  - Disruption of the mouse mTOR gene leads to early postimplantation lethality and
      prohibits embryonic stem cell development.
AB  - The mammalian target of rapamycin (mTOR) is a key component of a signaling
      pathway which integrates inputs from nutrients and growth factors to regulate
      cell growth. Recent studies demonstrated that mice harboring an ethylnitrosourea
      induced mutation in the gene encoding mTOR die at embryonic day 12.5 (E12.5).
      However, others have shown that the treatment of E4.5 blastocysts with rapamycin
      blocks trophoblast outgrowth, suggesting that the absence of mTOR should lead to
      embryonic lethality at an earlier stage. To resolve this discrepancy, we set out
      to disrupt the mTOR gene and analyze the outcome in both heterozygous and
      homozygous settings. Heterozygous mTOR (mTOR(+/-)) mice do not display any overt
      phenotype, although mouse embryonic fibroblasts derived from these mice show a
      50% reduction in mTOR protein levels and phosphorylation of S6 kinase 1 T389, a
      site whose phosphorylation is directly mediated by mTOR. However, S6
      phosphorylation, raptor levels, cell size, and cell cycle transit times are not
      diminished in these cells. In contrast to the situation in mTOR(+/-) mice,
      embryonic development of homozygous mTOR(-/-) mice appears to be arrested at
      E5.5; such embryos are severely runted and display an aberrant developmental
      phenotype. The ability of these embryos to implant corresponds to a limited level
      of trophoblast outgrowth in vitro, reflecting a maternal mRNA contribution, which
      has been shown to persist during preimplantation development. Moreover, mTOR(-/-)
      embryos display a lesion in inner cell mass proliferation, consistent with the
      inability to establish embryonic stem cells from mTOR(-/-) embryos.

PMID- 15485919
TI  - The proneural proteins Atonal and Scute regulate neural target genes through
      different E-box binding sites.
AB  - For a particular functional family of basic helix-loop-helix (bHLH) transcription
      factors, there is ample evidence that different factors regulate different target
      genes but little idea of how these different target genes are distinguished. We
      investigated the contribution of DNA binding site differences to the
      specificities of two functionally related proneural bHLH transcription factors
      required for the genesis of Drosophila sense organ precursors (Atonal and Scute).
      We show that the proneural target gene, Bearded, is regulated by both Scute and
      Atonal via distinct E-box consensus binding sites. By comparing with other Ato
      dependent enhancer sequences, we define an Ato-specific binding consensus that
      differs from the previously defined Scute-specific E-box consensus, thereby
      defining distinct E(Ato) and E(Sc) sites. These E-box variants are crucial for
      function. First, tandem repeats of 20-bp sequences containing E(Ato) and E(Sc)
      sites are sufficient to confer Atonal- and Scute-specific expression patterns,
      respectively, on a reporter gene in vivo. Second, interchanging E(Ato) and E(Sc)
      sites within enhancers almost abolishes enhancer activity. While the latter
      finding shows that enhancer context is also important in defining how proneural
      proteins interact with these sites, it is clear that differential utilization of
      DNA binding sites underlies proneural protein specificity.

PMID- 15485920
TI  - Disruption of the Rb--Raf-1 interaction inhibits tumor growth and angiogenesis.
AB  - The retinoblastoma tumor suppressor protein (Rb) plays a vital role in regulating
      mammalian cell cycle progression and inactivation of Rb is necessary for entry
      into S phase. Rb is inactivated by phosphorylation upon growth factor stimulation
      of quiescent cells, facilitating the transition from G(1) phase to S phase.
      Although the signaling events after growth factor stimulation have been well
      characterized, it is not yet clear how these signals contact the cell cycle
      machinery. We had found previously that growth factor stimulation of quiescent
      cells lead to the direct binding of Raf-1 kinase to Rb, leading to its
      inactivation. Here we show that the Rb-Raf-1 interaction occurs prior to the
      activation of cyclin and/or cyclin-dependent kinases and facilitates normal cell
      cycle progression. Raf-1-mediated inactivation of Rb is independent of the
      mitogen-activated protein kinase cascade, as well as cyclin-dependent kinases.
      Binding of Raf-1 seemed to correlate with the dissociation of the chromatin
      remodeling protein Brg1 from Rb. Disruption of the Rb-Raf-1 interaction by a nine
      amino-acid peptide inhibits Rb phosphorylation, cell proliferation, and vascular
      endothelial growth factor-mediated capillary tubule formation. Delivery of this
      peptide by a carrier molecule led to a 79% reduction in tumor volume and a 57%
      reduction in microvessel formation in nude mice. It appears that Raf-1 links
      mitogenic signaling to Rb and that disruption of this interaction could aid in
      controlling proliferative disorders.

PMID- 15485921
TI  - Recruitment of the Swi/Snf complex by Ste12-Tec1 promotes Flo8-Mss11-mediated
      activation of STA1 expression.
AB  - In the yeast Saccharomyces diastaticus, expression of the STA1 gene, which
      encodes an extracellular glucoamylase, is activated by the specific DNA-binding
      activators Flo8, Mss11, Ste12, and Tec1 and the Swi/Snf chromatin-remodeling
      complex. Here we show that Flo8 interacts physically and functionally with Mss11.
      Flo8 and Mss11 bind cooperatively to the inverted repeat sequence TTTGC-n-GCAAA
      (n = 97) in UAS1-2 of the STA1 promoter. In addition, Flo8 and Mss11 bind
      indirectly to UAS2-1 of the STA1 promoter by interacting with Ste12 and Tec1,
      which bind to the filamentation and invasion response element (FRE) in UAS2-1.
      Furthermore, our findings indicate that the Ste12, Tec1, Flo8, and Mss11
      activators and the Swi/Snf complex bind sequentially to the STA1 promoter, as
      follows: Ste12 and Tec1 bind first to the FRE, whereby they recruit the Swi/Snf
      complex to the STA1 promoter. Next, the Swi/Snf complex enhances Flo8 and Mss11
      binding to UAS1-2. In the final step, Flo8 and Mss11 directly promote association
      of RNA polymerase II with the STA1 promoter to activate STA1 expression. In the
      absence of glucose, the levels of Flo8 and Tec1 are greatly increased, whereas
      the abundances of two repressors, Nrg1 and Sfl1, are reduced, suggesting that the
      balance of transcriptional regulators may be important for determining activation
      or repression of STA1 expression.

PMID- 15485922
TI  - Fission yeast Dna2 is required for generation of the telomeric single-strand
      overhang.
AB  - It has been suggested that the Schizosaccharomyces pombe Rad50 (Rad50-Rad32-Nbs1)
      complex is required for the resection of the C-rich strand at telomere ends in
      taz1-d cells. However, the nuclease-deficient Rad32-D25A mutant can still resect
      the C-rich strand, suggesting the existence of a nuclease that resects the C-rich
      strand. Here, we demonstrate that a taz1-d dna2-2C double mutant lost the G-rich
      overhang at a semipermissive temperature. The amount of G-rich overhang in S
      phase in the dna2-C2 mutant was lower than that in wild-type cells at the
      semipermissive temperature. Dna2 bound to telomere DNA in a chromatin
      immunoprecipitation assay. Moreover, telomere length decreased with each
      generation after shift of the dna2-2C mutant to the semipermissive temperature.
      These results suggest that Dna2 is involved in the generation of G-rich overhangs
      in both wild-type cells and taz1-d cells. The dna2-C2 mutant was not gamma ray
      sensitive at the semipermissive temperature, suggesting that the ability to
      process double-strand break (DSB) ends was not affected in the dna2-C2 mutant.
      Our results reveal that DSB ends and telomere ends are processed by different
      mechanisms.

PMID- 15485923
TI  - A coordinated temporal interplay of nucleosome reorganization factor, sister
      chromatin cohesion factor, and DNA polymerase alpha facilitates DNA replication.
AB  - DNA replication depends critically upon chromatin structure. Little is known
      about how the replication complex overcomes the nucleosome packages in chromatin
      during DNA replication. To address this question, we investigate factors that
      interact in vivo with the principal initiation DNA polymerase, DNA polymerase
      alpha (Polalpha). The catalytic subunit of budding yeast Polalpha (Pol1p) has
      been shown to associate in vitro with the Spt16p-Pob3p complex, a component of
      the nucleosome reorganization system required for both replication and
      transcription, and with a sister chromatid cohesion factor, Ctf4p. Here, we show
      that an N-terminal region of Polalpha (Pol1p) that is evolutionarily conserved
      among different species interacts with Spt16p-Pob3p and Ctf4p in vivo. A mutation
      in a glycine residue in this N-terminal region of POL1 compromises the ability of
      Pol1p to associate with Spt16p and alters the temporal ordered association of
      Ctf4p with Pol1p. The compromised association between the chromatin-reorganizing
      factor Spt16p and the initiating DNA polymerase Pol1p delays the Pol1p assembling
      onto and disassembling from the late-replicating origins and causes a slowdown of
      S-phase progression. Our results thus suggest that a coordinated temporal and
      spatial interplay between the conserved N-terminal region of the Polalpha protein
      and factors that are involved in reorganization of nucleosomes and promoting
      establishment of sister chromatin cohesion is required to facilitate S-phase
      progression.

PMID- 15485924
TI  - CK2 is responsible for phosphorylation of human La protein serine-366 and can
      modulate rpL37 5'-terminal oligopyrimidine mRNA metabolism.
AB  - La protein binds precursors to 5S rRNA, tRNAs, and other transcripts that contain
      3' UUU-OH and also promotes their maturation in the nucleus. Separate from this
      function, human La has been shown to positively modulate the translation of mRNAs
      that contain complex 5' regulatory motifs that direct internal initiation of
      translation. Nonphosphorylated La (npLa) inhibits pre-tRNA processing, while
      phosphorylation of human La serine-366 (S(366)) promotes pre-tRNA processing.
      npLa was found specifically associated with a class of mRNAs that have unusually
      short 5' untranslated regions comprised of terminal oligopyrimidine (5'TOP)
      tracts and that encode ribosomal proteins and translation elongation factors.
      Although La S(366) represents a CK2 phosphorylation site, there was no evidence
      that CK2 phosphorylates it in vivo. We used the CK2-specific inhibitor, 4,5,6,7
      tetrabromo-2-azabenzimidazole (TBB), and antisense-mediated knockdown to
      demonstrate that CK2 is responsible for La S(366) phosphorylation in vivo.
      Hypophosphorylation was not associated with significant change in total La levels
      or proteolytic cleavage. Quantitative reverse transcription-PCR revealed
      increased association of the 5'TOP-mRNA encoding ribosomal protein L37 (rpL37)
      with La after TBB treatment. Transfection revealed more rpL37 mRNA associated
      with nonphosphorylatable La A(366) than with La S(366), concomitant with La
      A(366)-specific shift of a fraction of L37 mRNA off polysomes. The data indicate
      that CK2 phosphorylates La S(366) in vivo, that this limits 5'TOP mRNA binding,
      and that increasing npLa leads to greater association with potentially negative
      effects on TOP mRNA translation. Consistent with data that indicate that
      phosphorylation reverses negative effects of npLa on tRNA production, the present
      data suggest that CK2 phosphorylation of La can affect production of the
      translational machinery.

PMID- 15485925
TI  - Interferon-inducible ubiquitin E2, Ubc8, is a conjugating enzyme for protein
      ISGylation.
AB  - Protein ISGylation is unique among ubiquitin-like conjugation systems in that the
      expression and conjugation processes are induced by specific stimuli, mainly via
      the alpha/beta interferon signaling pathway. It has been suggested that protein
      ISGylation plays a special role in the immune response, because of its interferon
      signal dependency and its appearance only in higher eukaryotic organisms. Here,
      we report the identification of an ISG15-conjugating enzyme, Ubc8. Like other
      components of the protein ISGylation system (ISG15, UBE1L, and UBP43), Ubc8 is an
      interferon-inducible protein. Ubc8 clearly mediates protein ISGylation in
      transfection assays. The reduction of Ubc8 expression by small interfering RNA
      causes a decrease in protein ISGylation in HeLa cells upon interferon treatment.
      Neither UbcH7/UbcM4, the closest homologue of Ubc8 among known ubiquitin E2s, nor
      the small ubiquitin-like modifier E2 Ubc9 supports protein ISGylation. These
      findings strongly suggest that Ubc8 is a major ISG15-conjugating enzyme
      responsible for protein ISGylation upon interferon stimulation. Furthermore, we
      established an assay system to detect ISGylated target proteins by cotransfection
      of ISG15, UBE1L, and Ubc8 together with a target protein to be analyzed. This
      method provides an easy and effective way to identify new targets for the
      ISGylation system and will facilitate related studies.

PMID- 15485926
TI  - FoxA proteins regulate H19 endoderm enhancer E1 and exhibit developmental changes
      in enhancer binding in vivo.
AB  - Multiple enhancers govern developmental and tissue-specific expression of the H19
      Igf2 locus, but factors that bind these elements have not been identified. Using
      chromatin immunoprecipitation, we have found two FoxA binding sites in the H19 E1
      enhancer. Mutating these sites diminishes E1 activity in hepatoma cells.
      Additional chromatin immunoprecipitations show that FoxA binds to E1 in fetal
      liver, where H19 is abundantly expressed, but that binding decreases in adult
      liver, where H19 is no longer transcribed, even though FoxA proteins are present
      at both times. FoxA proteins are induced when F9 embryonal carcinoma cells
      differentiate into visceral endoderm (VE) and parietal endoderm (PE). We show
      that FoxA binds E1 in VE cells, where H19 is expressed, but not in PE cells,
      where H19 is silent. This correlation between FoxA binding and H19 expression
      indicates a role for FoxA in regulating H19, including developmental activation
      in the yolk sac and liver and postnatal repression in the liver. This is the
      first demonstration of a tissue-specific factor involved in developmental control
      of H19 expression. These data also indicate that the presence of FoxA proteins is
      not sufficient for binding but that additional mechanisms must govern the
      accessibility of FoxA proteins to their cognate binding sites within the H19 E1
      enhancer.

PMID- 15485927
TI  - Functional characterization of a Trypanosoma brucei TATA-binding protein-related
      factor points to a universal regulator of transcription in trypanosomes.
AB  - Transcriptional mechanisms remain poorly understood in trypanosomatid protozoa.
      In particular, there is no knowledge about the function of basal transcription
      factors, and there is an apparent rarity of promoters for protein-coding genes
      transcribed by RNA polymerase (Pol) II. Here we describe a Trypanosoma brucei
      factor related to the TATA-binding protein (TBP). Although this TBP-related
      factor (TBP-related factor 4 [TRF4]) has about 31% identity to the TBP core
      domain, several key residues involved in TATA box binding are not conserved.
      Depletion of the T. brucei TRF4 (TbTRF4) by RNA interference revealed an
      essential role in RNA Pol I, II, and III transcription. Using chromatin
      immunoprecipitation, we further showed that TRF4 is recruited to the Pol I
      transcribed procyclic acidic repetitive genes, Pol II-transcribed spliced leader
      RNA genes, and Pol III-transcribed U-snRNA and 7SL RNA genes, thus supporting a
      role for TbTRF4 in transcription performed by all three nuclear RNA polymerases.
      Finally, a search for TRF4 binding sites in the T. brucei genome led to the
      identification of such sites in the 3' portion of certain protein-coding genes,
      indicating a unique aspect of Pol II transcription in these organisms.

PMID- 15485928
TI  - Both BC-box motifs of adenovirus protein E4orf6 are required to efficiently
      assemble an E3 ligase complex that degrades p53.
AB  - Small DNA tumor viruses typically encode proteins that either inactivate or
      degrade p53. Human adenoviruses encode products, including E4orf6 and E1B55K,
      that do both. Each independently binds to p53 and inhibits its ability to
      activate gene expression; however, in combination they induce p53 degradation by
      the ubiquitin pathway. We have shown previously that p53 degradation relies on
      interactions of E4orf6 with the cellular proteins Cul5, Rbx1, and elongins B and
      C to form an E3 ligase similar to the SCF and VBC complexes. Here we show that,
      like other elongin BC-interacting proteins, including elongin A, von Hippel
      Lindau protein, and Muf1, the interaction of E4orf6 is mediated by the BC-box
      motif; however, E4orf6 uniquely utilizes two BC-box motifs for degradation of p53
      and another target, Mre11. In addition, our data suggest that the interaction of
      E1B55K with E4orf6 depends on the ability of E4orf6 to form the E3 ligase complex
      and that such complex formation may be required for all E4orf6-E1B55K functions.

PMID- 15485929
TI  - Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively
      regulates expression of ST7 and NM23 tumor suppressor genes.
AB  - Protein arginine methyltransferases (PRMTs) have been implicated in
      transcriptional activation and repression, but their role in controlling cell
      growth and proliferation remains obscure. We have recently shown that PRMT5 can
      interact with flag-tagged BRG1- and hBRM-based hSWI/SNF chromatin remodelers and
      that both complexes can specifically methylate histones H3 and H4. Here we report
      that PRMT5 can be found in association with endogenous hSWI/SNF complexes, which
      can methylate H3 and H4 N-terminal tails, and show that H3 arginine 8 and H4
      arginine 3 are preferred sites of methylation by recombinant and hSWI/SNF
      associated PRMT5. To elucidate the role played by PRMT5 in gene regulation, we
      have established a PRMT5 antisense cell line and determined by microarray
      analysis that more genes are derepressed when PRMT5 levels are reduced. Among the
      affected genes, we show that suppressor of tumorigenicity 7 (ST7) and
      nonmetastatic 23 (NM23) are direct targets of PRMT5-containing BRG1 and hBRM
      complexes. Furthermore, we demonstrate that expression of ST7 and NM23 is reduced
      in a cell line that overexpresses PRMT5 and that this decrease in expression
      correlates with H3R8 methylation, H3K9 deacetylation, and increased
      transformation of NIH 3T3 cells. These findings suggest that the BRG1- and hBRM
      associated PRMT5 regulates cell growth and proliferation by controlling
      expression of genes involved in tumor suppression.

PMID- 15485930
TI  - Nuclear pre-mRNA decapping and 5' degradation in yeast require the Lsm2-8p
      complex.
AB  - Previous analyses have identified related cytoplasmic Lsm1-7p and nuclear Lsm2-8p
      complexes. Here we report that mature heat shock and MET mRNAs that are trapped
      in the nucleus due to a block in mRNA export were strongly stabilized in strains
      lacking Lsm6p or the nucleus-specific Lsm8p protein but not by the absence of the
      cytoplasmic Lsm1p. These nucleus-restricted mRNAs remain polyadenylated until
      their degradation, indicating that nuclear mRNA degradation does not involve the
      incremental deadenylation that is a key feature of cytoplasmic turnover. Lsm8p
      can be UV cross-linked to nuclear poly(A)(+) RNA, indicating that an Lsm2-8p
      complex interacts directly with nucleus-restricted mRNA. Analysis of pre-mRNAs
      that contain intronic snoRNAs indicates that their 5' degradation is specifically
      inhibited in strains lacking any of the Lsm2-8p proteins but Lsm1p. Nucleus
      restricted mRNAs and pre-mRNA degradation intermediates that accumulate in lsm
      mutants remain 5' capped. We conclude that the Lsm2-8p complex normally targets
      nuclear RNA substrates for decapping.

PMID- 15485931
TI  - Lipopolysaccharide activation of the TPL-2/MEK/extracellular signal-regulated
      kinase mitogen-activated protein kinase cascade is regulated by IkappaB kinase
      induced proteolysis of NF-kappaB1 p105.
AB  - The MEK kinase TPL-2 (also known as Cot) is required for lipopolysaccharide (LPS)
      activation of the extracellular signal-regulated kinase (ERK) mitogen-activated
      protein (MAP) kinase cascade in macrophages and consequent upregulation of genes
      involved in innate immune responses. In resting cells, TPL-2 forms a
      stoichiometric complex with NF-kappaB1 p105, which negatively regulates its MEK
      kinase activity. Here, it is shown that lipopolysaccharide (LPS) stimulation of
      primary macrophages causes the release of both long and short forms of TPL-2 from
      p105 and that TPL-2 MEK kinase activity is restricted to this p105-free pool.
      Activation of TPL-2, MEK, and ERK by LPS is also demonstrated to require
      proteasome-mediated proteolysis. p105 is known to be proteolysed by the
      proteasome following stimulus-induced phosphorylation of two serines in its PEST
      region by the IkappaB kinase (IKK) complex. Expression of a p105 point mutant,
      which is not susceptible to signal-induced proteolysis, in RAW264.7 macrophages
      impairs LPS-induced release of TPL-2 from p105 and its subsequent activation of
      MEK. Furthermore, expression of wild-type but not mutant p105 reconstitutes LPS
      stimulation of MEK and ERK phosphorylation in primary NF-kappaB1-deficient
      macrophages. Consistently, pharmacological blockade of IKK inhibits LPS-induced
      release of TPL-2 from p105 and TPL-2 activation. These data show that IKK-induced
      p105 proteolysis is essential for LPS activation of TPL-2, thus revealing a novel
      function of IKK in the regulation of the ERK MAP kinase cascade.

PMID- 15485932
TI  - Serine phosphorylation proximal to its phosphotyrosine binding domain inhibits
      insulin receptor substrate 1 function and promotes insulin resistance.
AB  - Ser/Thr phosphorylation of insulin receptor substrate (IRS) proteins negatively
      modulates insulin signaling. Therefore, the identification of serine sites whose
      phosphorylation inhibit IRS protein functions is of physiological importance.
      Here we mutated seven Ser sites located proximal to the phosphotyrosine binding
      domain of insulin receptor substrate 1 (IRS-1) (S265, S302, S325, S336, S358,
      S407, and S408) into Ala. When overexpressed in rat hepatoma Fao or CHO cells,
      the mutated IRS-1 protein in which the seven Ser sites were mutated to Ala (IRS
      1(7A)), unlike wild-type IRS-1 (IRS-1(WT)), maintained its Tyr-phosphorylated
      active conformation after prolonged insulin treatment or when the cells were
      challenged with inducers of insulin resistance prior to acute insulin treatment.
      This was due to the ability of IRS-1(7A) to remain complexed with the insulin
      receptor (IR), unlike IRS-1(WT), which underwent Ser phosphorylation, resulting
      in its dissociation from IR. Studies of truncated forms of IRS-1 revealed that
      the region between amino acids 365 to 430 is a main insulin-stimulated Ser
      phosphorylation domain. Indeed, IRS-1 mutated only at S408, which undergoes
      phosphorylation in vivo, partially maintained the properties of IRS-1(7A) and
      conferred protection against selected inducers of insulin resistance. These
      findings suggest that S408 and additional Ser sites among the seven mutated Ser
      sites are targets for IRS-1 kinases that play a key negative regulatory role in
      IRS-1 function and insulin action. These sites presumably serve as points of
      convergence, where physiological feedback control mechanisms, which are triggered
      by insulin-stimulated IRS kinases, overlap with IRS kinases triggered by inducers
      of insulin resistance to terminate insulin signaling.

PMID- 15485933
TI  - The Mre11 nuclease is not required for 5' to 3' resection at multiple HO-induced
      double-strand breaks.
AB  - Current hypotheses suggest the Mre11 nuclease activity could be directly involved
      in double-strand break (DSB) resection in the presence of a large number of DSBs
      or limited to processing abnormal DNA ends. To distinguish between these
      possibilities, we used two methods to create large numbers of DSBs in
      Saccharomyces cerevisiae chromosomes, without introducing other substrates for
      the Mre11 nuclease. Multiple DSBs were created either by expressing the HO
      endonuclease in strains containing several HO cut sites embedded within randomly
      dispersed Ty1 elements or by phleomycin treatment. Analysis of resection by
      single-strand DNA formation in these systems showed no difference between strains
      containing MRE11 or the mre11-D56N nuclease defective allele, suggesting that the
      Mre11 nuclease is not involved in the extensive 5' to 3' resection of DSBs. We
      postulate that the ionizing radiation (IR) sensitivity of mre11 nuclease
      defective mutants results from the accumulation of IR-induced DNA damage that is
      normally processed by the Mre11 nuclease. We also report that the processivity of
      5' to 3' DSB resection and the yield of repaired products are affected by the
      number of DSBs in a dose-dependent manner. Finally, we show that the exonuclease
      Exo1 is involved in the processivity of 5' to 3' resection of an HO-induced DSB
      at the MAT locus.

PMID- 15485936
TI  - Email in clinical care.

PMID- 15485934
TI  - The Lambeth Early Onset (LEO) Team: randomised controlled trial of the
      effectiveness of specialised care for early psychosis.
AB  - OBJECTIVE: To evaluate the effectiveness of a service for early psychosis.
      DESIGN: Randomised controlled clinical trial. SETTING: Community mental health
      teams in one London borough. PARTICIPANTS: 144 people aged 16-40 years presenting
      to mental health services for the first or second time with non-organic, non
      affective psychosis. INTERVENTIONS: Assertive outreach with evidence based
      biopsychosocial interventions (specialised care group) and standard care (control
      group) delivered by community mental health teams. PRIMARY OUTCOME MEASURES:
      Rates of relapse and readmission to hospital. RESULTS: Compared with patients in
      the standard care group, those in the specialised care group were less likely to
      relapse (odds ratio 0.46, 95% confidence interval 0.22 to 0.97), were readmitted
      fewer times (beta 0.39, 0.10 to 0.68), and were less likely to drop out of the
      study (odds ratio 0.35, 0.15 to 0.81). When rates were adjusted for sex, previous
      psychotic episode, and ethnicity, the difference in relapse was no longer
      significant (odds ratio 0.55, 0.24 to 1.26); only total number of readmissions
      (beta 0.36, 0.04 to 0.66) and dropout rates (beta 0.28, 0.12 to 0.73) remained
      significant. CONCLUSIONS: Limited evidence shows that a team delivering
      specialised care for patients with early psychosis is superior to standard care
      for maintaining contact with professionals and for reducing readmissions to
      hospital. No firm conclusions can, however, be drawn owing to the modest sample
      size.

PMID- 15485935
TI  - National cross sectional study of views on sexual violence and risk of HIV
      infection and AIDS among South African school pupils.
AB  - OBJECTIVE: To investigate the views of school pupils on sexual violence and on
      the risk of HIV infection and AIDS and their experiences of sexual violence.
      DESIGN: National cross sectional study. SETTING: 5162 classes in 1418 South
      African schools. PARTICIPANTS: 269,705 school pupils aged 10-19 years in grades 6
      11. MAIN OUTCOME MEASURE: Answers to questions about sexual violence and about
      the risk of HIV infection and AIDS. RESULTS: Misconceptions about sexual violence
      were common among both sexes, but more females held views that would put them at
      high risk of HIV infection. One third of the respondents thought they might be
      HIV positive. This was associated with misconceptions about sexual violence and
      about the risk of HIV infection and AIDS. Around 11% of males and 4% of females
      claimed to have forced someone else to have sex; 66% of these males and 71% of
      these females had themselves been forced to have sex. A history of forced sex was
      a powerful determinant of views on sexual violence and risk of HIV infection.
      CONCLUSIONS: The views of South African youth on sexual violence and on the risk
      of HIV infection and AIDS were compatible with acceptance of sexual coercion and
      "adaptive" attitudes to survival in a violent society. Views differed little
      between the sexes.

PMID- 15485937
TI  - Interview with National Health Information Technology Coordinator David Brailer,
      MD, PhD.

PMID- 15485938
TI  - Lessons from the withdrawal of rofecoxib.

PMID- 15485939
TI  - The scandal of poor epidemiological research.

PMID- 15485941
TI  - Primary care trusts.

PMID- 15485940
TI  - Self monitoring of blood pressure at home.

PMID- 15485942
TI  - Seriously ill elderly patients are subjected to futile endoscopies.

PMID- 15485944
TI  - Patient held informally in hospital had his rights violated.

PMID- 15485945
TI  - Second drug firm found guilty of "switching" patients to new drugs.

PMID- 15485946
TI  - Baby should be allowed to die, UK court rules.

PMID- 15485947
TI  - US experts urge more neonatal screening for genetic disorders.

PMID- 15485948
TI  - South East Asia sets up task force to tackle avian flu.

PMID- 15485949
TI  - Factory's loss of licence halves supply of flu vaccine to US.

PMID- 15485950
TI  - WMA says trial participants must have access to best treatment when a trial ends.

PMID- 15485951
TI  - WMA sets rules on how doctors handle industry sponsorship.

PMID- 15485953
TI  - UK government acts to curb rise in tuberculosis.

PMID- 15485957
TI  - Indian regulators are accused of laxity in not banning drugs.

PMID- 15485959
TI  - Website of patients' experiences launches new module on depression.

PMID- 15485963
TI  - Eight cases of parents convicted of killing their children are referred to
      commission.

PMID- 15485964
TI  - Prescribing of antibiotics and admissions for respiratory tract infections in
      England.

PMID- 15485966
TI  - Introduction of nurse led DC cardioversion service in day surgery unit:
      prospective audit.
AB  - PROBLEM: Atrial fibrillation is the most common persistent arrhythmia in adults
      and carries an increased risk of thromboembolism and stroke. Electrical (DC)
      cardioversion is an effective treatment, but logistical difficulties in many
      institutions lead to problems providing a prompt service. This reduces the rate
      of long term success, delays relief of symptoms, and increases the burden on
      anticoagulation clinics. DESIGN: Prospective audit of introduction of a
      collaborative, nurse led DC cardioversion service in a day surgery unit. SETTING:
      Day surgery unit 5 km from an acute hospital in southeast London. KEY MEASURES
      FOR IMPROVEMENT: Waiting times, success of procedures, and complication rates.
      STRATEGIES FOR CHANGE: Collaborative working across traditional specialty
      boundaries; empowerment of patients within the process; using a nurse consultant
      as a single point of reference to coordinate the service. EFFECTS OF CHANGE:
      Sinus rhythm was restored in 131 (92%) of the first 143 patients treated. Three
      patients needed hospital admission; all were discharged uneventfully within 24
      hours. No important complications occurred. Waiting times were reduced from 27
      weeks to eight weeks for patients eligible for the service. LESSONS LEARNT:
      Elective DC cardioversion under general anaesthesia can be safely done by an
      appropriately trained nurse in a day surgery unit remote from an acute general
      hospital. This model of care is effective and can reduce waiting times and
      relieve pressure on acute beds and junior doctors.

PMID- 15485965
TI  - Familial risk of urinary incontinence in women: population based cross sectional
      study.
AB  - OBJECTIVE: To determine whether there is an increased risk of urinary
      incontinence in daughters and sisters of incontinent women. DESIGN: Population
      based cross sectional study. SETTING: EPINCONT (the epidemiology of incontinence
      in the county of Nord-Trondelag study), a substudy of HUNT 2 (the Norwegian Nord
      Trondelag health survey 2), 1995-7. PARTICIPANTS: 6021 mothers, 7629 daughters,
      332 granddaughters, and 2104 older sisters of 2426 sisters. MAIN OUTCOME
      MEASURES: Adjusted relative risks for urinary incontinence. RESULTS: The
      daughters of mothers with urinary incontinence had an increased risk for urinary
      incontinence (1.3, 95% confidence interval 1.2 to 1.4; absolute risk 23.3%),
      stress incontinence (1.5, 1.3 to 1.8; 14.6%), mixed incontinence (1.6, 1.2 to
      2.0; 8.3%), and urge incontinence (1.8, 0.8 to 3.9; 2.6%). If mothers had severe
      symptoms then their daughters were likely to have such symptoms (1.9, 1.3 to 3.0;
      4.0%). The younger sisters of female siblings with urinary incontinence, stress
      incontinence, or mixed incontinence had increased relative risks of,
      respectively, 1.6 (1.3 to 1.9; absolute risk 29.6%), 1.8 (1.3 to 2.3; 18.3%), and
      1.7 (1.1 to 2.8; 10.8%). CONCLUSION: Women are more likely to develop urinary
      incontinence if their mother or older sisters are incontinent.

PMID- 15485967
TI  - Recent developments: suicide in older people.

PMID- 15485974
TI  - Moving the preterm infant.

PMID- 15485975
TI  - Use of stimulants for attention deficit hyperactivity disorder: FOR.

PMID- 15485976
TI  - Use of stimulants for attention deficit hyperactivity disorder: AGAINST.

PMID- 15485977
TI  - Managing comorbidities in patients at the end of life.

PMID- 15485978
TI  - Classifying kidney problems: can we avoid framing risks as diseases?

PMID- 15485979
TI  - Consent to the publication of patient information: seeking consent is morally
      essential.

PMID- 15485980
TI  - Consent to the publication of patient information: more on confidentiality and
      case material.

PMID- 15485981
TI  - Consent to the publication of patient information: incompetent patients may pose
      a problem.

PMID- 15485982
TI  - Feeding tubes in dementia: is there an effective UK strategy?

PMID- 15485983
TI  - People with intellectual disabilities: people registered disabled with learning
      difficulties tend to fall through the net.

PMID- 15485984
TI  - People with intellectual disabilities: emotional needs of children with
      intellectual disabilities are unidentified.

PMID- 15485985
TI  - Salt tax could reduce population's salt intake.

PMID- 15485986
TI  - Best estimates of coronary risk of passive smoking are needed.

PMID- 15485987
TI  - Liver toxicity and pioglitazone: data are missing.

PMID- 15485992
TI  - High throughput screening of methylation status of genes in prostate cancer using
      an oligonucleotide methylation array.
AB  - Recent work using high-throughput microarray technology has discovered altered
      expression of a large number of genes in prostate cancer. Many of these
      alterations may be the consequence of changes in methylation status in the CpG
      islands of promoter or exon 1 regions of these genes. In order to determine the
      methylation status of a large number of genes and ESTs we combined the principle
      of match/mismatch hybridization with the technique of whole genome labeling to
      develop a highly specific oligonucleotide-based methylation microarray. Using
      this array, we analyzed the methylation status of 105 genes and ESTs in three
      prostate cancer cell lines. Between 32 and 47% of these genes and ESTs were
      methylated in these cell lines. By correlating the methylation status of this
      array with the results of Affymetrix expression arrays of three prostate cancer
      cell lines, we determined that methylation of genes played a significant role
      (37%) in down-regulating the expression of certain genes in prostate cancer. We
      also tested this array on a number of primary prostate tissue samples. Our
      results indicated that a subset of genes in this microarray (25/105) were
      methylated in all prostate cancer samples but not in normal prostate, suggesting
      the potential significance of alterations in the methylation status of certain
      genes in the development of prostate cancer.

PMID- 15485993
TI  - 15-deoxy-Delta-12,14-prostaglandin J2 induces programmed cell death of breast
      cancer cells by a pleiotropic mechanism.
AB  - Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) has
      been found to induce cell death in a variety of cells. In this regard, we
      reported recently that 15-deoxy-Delta-(12,14)-prostaglandin J2 (15dPG-J2), a
      specific ligand of the nuclear receptor PPARgamma, inhibits proliferation and
      induces cellular differentiation and apoptosis in the breast cancer cell line MCF
      7. In addition to PPARgamma activation other proteins, such as NF-kappaB and AP1,
      have been shown to be targets of 15dPG-J2. However, the mechanism by which 15dPG
      J2 triggers cell death is still elusive. Our results demonstrate that 15dPG-J2
      initiates breast cancer cell death via a very rapid and severe impairment of
      mitochondrial function, as revealed by a drop in mitochondrial membrane potential
      (DeltaPsi(m)), generation of reactive oxygen species (ROS) and a decrease in
      oxygen consumption. In addition, 15dPG-J2 can also activate an intrinsic
      apoptotic pathway involving phosphatidyl serine externalization, caspase
      activation and cytochrome c release. Bcl-2 over-expression and zVADfmk, albeit
      preventing caspase activation, have no effect on 15dPG-J2-mediated mytochondrial
      dysfunction and loss of cell viability. In contrast, the addition of radical
      scavengers or rotenone, which prevent 15dPG-J2-induced ROS production, block the
      loss of cell viability induced by this prostaglandin. Finally, 15dPG-J2-induced
      cell death appears to involve disruption of the microtubule cytoskeletal network.
      Together, these results suggest that PG-J2-induced mitochondrial dysfunction and
      ROS production inevitably leads to death, with or without caspases.

PMID- 15485994
TI  - Polymorphism of the p73 gene in relation to colorectal cancer risk and survival.
AB  - The results regarding a GC/AT polymorphism in the p73 gene in relation to cancer
      risk are inconsistent, and the significance of loss of heterozygosity (LOH) of
      the gene is unclear. In the present study, we investigated whether this
      polymorphism was related to the risk of colorectal cancer, and whether there were
      relationships between the polymorphism and LOH, protein expression or
      clinicopathological variables. 179 patients with colorectal cancer and 260
      healthy controls were genotyped for the polymorphism by PCR-restriction fragment
      length polymorphism (RFLP). Fifty informative cases were examined for LOH in
      tumours. Immunohistochemistry was performed on distant (n = 42) and adjacent
      normal mucosa (n = 33), primary tumour (n = 6 9) and lymph node metastasis (n =
      12). The frequencies of the genotypes were 63% for wild-type (GC/GC), 30% for
      heterozygotes (GC/AT) and 7% for variants (AT/AT) in patients, and 62, 36 and 2%
      in controls, respectively. The frequencies of the genotypes in the patients and
      controls were significantly different (P = 0.02). The patients carrying the AT
      allele had a better prognosis than those with the GC/GC genotype (OR = 0.42, 95%
      CI = 1.15-5.02, P = 0.02). No LOH was observed at the p73 locus. Expression of
      p73 protein was increased from normal mucosa to primary tumours (P = 0.02), but
      was not significantly changed between primary tumours and metastases (P = 1.0).
      In conclusion, the AT/AT homozygotes may have a greater risk of developing
      colorectal cancer, while the patients who carried the AT allele had a better
      prognosis.

PMID- 15485995
TI  - Relationship between serum trough infliximab levels, pretreatment C reactive
      protein levels, and clinical response to infliximab treatment in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the relationship between serum trough infliximab levels
      and clinical response to infliximab treatment in patients with rheumatoid
      arthritis (RA). METHODS: Disease activity and serum trough infliximab levels
      before and 2, 6, and 14 weeks after initiation of infliximab treatment at a dose
      of 3 mg/kg in a cohort of 105 patients with RA were assessed. Serum trough
      infliximab levels in responders and non-responders were compared. Additionally,
      the clinical responses of patients with high, intermediate, and low serum trough
      infliximab levels at 14 weeks were compared. RESULTS: After 14 weeks of treatment
      non-responders had lower serum trough levels of infliximab than responders
      (median (interquartile range) 0.5 (0.2-2.2) v 3.6 (1.4-8.2) mg/l; p<0.01)).
      Patients with low serum trough infliximab levels at 14 weeks had significantly
      less improvement in the 28 joint count Disease Activity Score (DAS28) score than
      patients with intermediate or high serum trough infliximab levels at 14 weeks.
      Pretreatment C reactive protein (CRP) levels correlated negatively with serum
      trough infliximab levels at 14 weeks after the start of treatment (Spearman rank
      correlation r(s) = -0.43, p<0.001). CONCLUSION: Serum trough levels of infliximab
      correlate with the clinical response to treatment with infliximab and
      pretreatment CRP levels. This study indicates that patients with high
      pretreatment CRP levels might benefit from higher dosages of infliximab or
      shorter dosing intervals.

PMID- 15485996
TI  - Expression and localisation of the new metalloproteinase inhibitor RECK
      (reversion inducing cysteine-rich protein with Kazal motifs) in inflamed synovial
      membranes of patients with rheumatoid arthritis.
AB  - OBJECTIVE: To assess the expression and localisation of the new metalloproteinase
      inhibitor RECK, an inhibitor of matrix metalloproteinase-14 (MMP-14) secretion
      and activity, in the synovial membrane of patients with rheumatoid arthritis
      (RA). METHODS: RECK expression in synovium samples from patients with RA,
      osteoarthritis (OA), and "trauma" were studied by quantitative real time reverse
      transcription-polymerase chain reaction (Q-PCR). RECK mRNA levels were compared
      with those of the enzyme MMP-14. RECK expression on cryostat sections of synovium
      was disclosed by goat-antihuman RECK monoclonal antibody. RECK protein was
      detected on synovial cryostat sections and measured by western blotting. RECK
      expression on macrophages was investigated by double staining of CD68 and RECK on
      cryostat sections and characterised by confocal microscopy. RECK expression on RA
      monocytes or normal monocytes was further investigated by FACS analysis. RESULTS:
      RECK expression in the synovial membrane of patients with RA was significantly
      lower than in OA and controls. MMP-14 mRNA levels were not significantly
      different between the three groups. In RA synovium, RECK protein was expressed
      mainly in the lining layer but also by macrophages around blood vessels.
      Fibroblasts and about 50% of the CD68 positive macrophages expressed RECK. In
      CD68 positive macrophages, RECK was only expressed in secretory granules and not
      on the membrane. The same pattern was found in M-CSF cultured macrophages of
      patients with RA and controls. In contrast, synovial fibroblasts showed a diffuse
      membrane expression within the synovium similar to cultured RA fibroblasts. RECK
      expression was low on the membrane of monocytes according to FACS analysis.
      CONCLUSION: The new MMP inhibitor RECK is expressed in synovial membranes of RA,
      OA, and controls. RECK mRNA is lowest in RA synovial membranes. In contrast with
      fibroblasts, macrophages in the synovium express RECK only cytoplasmically and
      not on their membrane.

PMID- 15485997
TI  - A family based study shows no association between rheumatoid arthritis and the
      PADI4 gene in a white French population.
AB  - BACKGROUND: Autoantibodies to citrullinated proteins (ACPA) are considered a
      specific marker for rheumatoid arthritis. Peptidylarginine deiminase (PAD) is the
      enzyme that converts arginyl into citrullyl residues; different isoforms of the
      enzyme are expressed in mammals. It has been suggested that the PADI4 gene may
      contribute to genetic susceptibility to rheumatoid arthritis, but conflicting
      results have been obtained in different populations. OBJECTIVE: To test the
      hypothesis that the PADI4 gene may confer susceptibility to rheumatoid arthritis
      in a white French population, using powerful and highly reliable family based
      association tests. METHODS: DNA samples were analysed from 100 families where one
      member was affected by rheumatoid arthritis and both parents were available for
      sampling. Five single nucleotide polymorphisms, located within the PADI4 gene and
      in its close proximity, were genotyped by restriction fragment length
      polymorphism, and haplotypes were constructed. The analysis involved use of the
      transmission disequilibrium test and genotype relative risk. ACPA were detected
      by ELISA on cyclic citrullinated peptides and on human deiminated fibrinogen.
      RESULTS: No single SNP or haplotype was associated with the disease, or was
      preferentially transmitted. No association was found when patients were
      partitioned according to ACPA positivity. CONCLUSIONS: No PADI4 haplotype is
      associated with rheumatoid arthritis in a white French population. The role of
      genes encoding the other PAD isoforms, or modulating tissue expression or enzyme
      activity, remains to be elucidated.

PMID- 15485999
TI  - Fluoroscope-aided retrograde placement of guide wire for tracheal intubation in
      patients with limited mouth opening.
AB  - Passing a retrograde catheter/wire into the pharynx through a cricothyroid
      puncture can facilitate tracheal intubation in difficult situations where either
      a flexible fibre-optic bronchoscope or an expert user of such a device is not
      available. Some mouth opening is essential for the oral and/or nasal retrieval of
      the catheter/wire from the pharynx. Two patients with temporo-mandibular joint
      (TMJ) ankylosis and extremely limited mouth opening required gap arthroplasty of
      the TMJ under general anaesthesia. Because we did not have a flexible fibre-optic
      bronchoscope, we performed fluoroscopy-assisted nasal retrieval of the guide wire
      passed up through a cricothyroid puncture and subsequently accomplished wire
      guided naso-tracheal intubation. In the absence of a flexible fibre-optic
      bronchoscope, this technique is a very useful aid to intubation in patients with
      limited mouth opening.

PMID- 15485998
TI  - Clinical interpretation of antineutrophil cytoplasmic antibodies: parvovirus B19
      infection as a pitfall.
AB  - BACKGROUND: While antibodies directed against proteinase 3 (PR3-ANCA) and
      myeloperoxidase (MPO-ANCA) have a high specificity for the diagnosis of systemic
      vasculitis, they may also be found as an epiphenomenon of acute viral infection.
      OBJECTIVE: To investigate whether positive ANCA test results may be a common
      feature of acute parvovirus B19 infection. METHODS: Sera were analysed from 1242
      patients from a rheumatology outpatient clinic for reactivity with parvovirus B19
      and EBV antibodies. They were tested for the presence of PR3-ANCA and MPO-ANCA,
      along with sera known to contain IgM antibodies to these viruses obtained from
      among 41,366 samples submitted for virological screening. RESULTS: ANCA were
      found in 10% (5/50) of the sera positive for IgM antibodies to parvovirus and in
      3/51 sera containing IgM antibodies to EBV. Three of six patients with arthritis
      and concomitant parvovirus infection were found positive for PR3-ANCA and two
      were found positive for MPO-ANCA. All six patients tested negative for ANCA after
      six months of follow up. CONCLUSIONS: PR3-ANCA and MPO-ANCA may occur transiently
      in patients with acute B19 infection or infectious mononucleosis, highlighting
      the importance of repeated antibody tests in oligosymptomatic clinical conditions
      in which systemic autoimmune disease is suspected.

PMID- 15486000
TI  - Prediction of tracheostomy tube size for paediatric long-term ventilation: an
      audit of children with spinal cord injury.
AB  - BACKGROUND: There are no published data to predict tracheostomy tube size as
      growth proceeds in children requiring long-term ventilation. METHODS: A
      retrospective audit was undertaken of children having long-term ventilation,
      managed from the Southport spinal injuries unit. The dates of step-up in size of
      tracheostomy tube were noted together with the tube inside and outside diameters
      (ID and OD) and the lateral tracheal diameter. The data were aggregated for each
      increment in tube size to calculate the Pearson correlation coefficients for age
      and weight of the children. Linear regression was then used to generate
      predictive equations based on age and weight. RESULTS: Out of 12 children, data
      from seven boys and two girls, with a mean age of 5.9 (range 1.5-13.75) yr, were
      obtained. Average length of follow-up was 7 yr, with an average of 3.5 tube
      changes per patient equating to a larger tube every 2 yr. The inside and outside
      tracheal tube diameters, as well as the lateral tracheal diameter, correlated
      significantly with age and weight (P<0.01). The appropriate tracheostomy tube
      internal diameter is conveniently expressed by the formula: ID mm=age yr/3 + 3.5
      CONCLUSIONS: The step-up in size of the tracheostomy tube as growth proceeds
      should be undertaken as a planned procedure at least every 2 yr to avoid
      nocturnal desaturation. Age appears to be a convenient and reliable predictor.

PMID- 15486001
TI  - Effect of obesity and thoracic epidural analgesia on perioperative spirometry.
AB  - BACKGROUND: Lung volumes in obese patients are reduced significantly in the
      postoperative period. As the effect of different analgesic regimes on
      perioperative spirometric tests in obese patients has not yet been studied, we
      investigated the effect of thoracic epidural analgesia and conventional opioid
      based analgesia on perioperative lung volumes measured by spirometry. METHODS:
      Eighty-four patients having midline laparotomy for gynaecological procedures
      successfully completed the study. Premedication, anaesthesia and analgesia were
      standardized. The patients were given a free choice between epidural analgesia
      (EDA) (n=42) or opioids (n=42) for postoperative analgesia. We performed
      spirometry to measure vital capacity (VC), forced vital capacity, peak expiratory
      flow, mid-expiratory flow and forced expiratory volume in 1 s at preoperative
      assessment, 30-60 min after premedication and 20 min, 1 h, 3 h and 6 h after
      extubation. RESULTS: Baseline values were all within the normal range. All
      perioperative spirometric values decreased significantly with increasing body
      mass index (BMI). The greatest reduction in VC occurred directly after
      extubation, but was less in the EDA group than in the opioid group: mean of 
      23(sd 8)% versus -30(12)% (P<0.001). In obese patients (BMI>30) the difference in
      VC was significantly more pronounced than in patients of normal weight (BMI<25): 
      45(10)% versus -33(4)% (P<0.001). Recovery of spirometric values was
      significantly quicker in patients receiving EDA, particularly in obese patients.
      CONCLUSION: We conclude that EDA should be considered in obese patients
      undergoing midline laparotomy to improve postoperative spirometry.

PMID- 15486002
TI  - Appropriate placement of intubation depth marks in a new cuffed paediatric
      tracheal tube.
AB  - BACKGROUND: The aim of this study was to evaluate the appropriateness of
      intubation depth marks on the new Microcuff paediatric tracheal tube. METHODS:
      With local Institutional Ethics Committee approval and informed parental consent,
      we included patients from birth (weighing > or =3 kg) to 16 yr who were
      undergoing general anaesthesia requiring orotracheal intubation. Tracheal
      intubation was performed using direct laryngoscopy, the intubation depth mark was
      placed between the vocal cords, and the tube was taped to the lateral corner of
      the mouth. The distance between the tube tip and the tracheal carina was assessed
      by flexible bronchoscopy with the patients in supine, and their head in neutral
      positions. Tube sizes were selected according to the formula: internal diameter
      (ID; mm)=(age/4)+3.5 in children > or =2 yr. In full-term newborns (> or =3 kg)
      to less than 1 yr ID 3.0 mm tubes were used and in children from 1 to less than 2
      yr ID 3.5 mm tubes were used. Endoscopic examination was performed in 50 size ID
      3.0 mm tubes, and in 25 tubes of each tube size from ID 3.5 to 7.0 mm. Tracheal
      length and percentage of the trachea to which the tube tip was advanced were
      calculated. RESULTS: 250 patients were studied (105 girls, 145 boys). The
      distance from the tube tip to the carina ranged from 1.4 cm in a 2-month-old
      infant (ID 3.0 mm) to 7.7 cm in a 14-yr-old boy (ID 7.0 mm). Mean tube insertion
      into the trachea was 53.2% (6.3) of tracheal length with a minimum of 40% and a
      maximum of 67.6%. CONCLUSIONS: The insertion depth marks of the new Microcuff
      paediatric tracheal tube allow adequate placing of the tracheal tube with a cuff
      free subglottic zone and without the risk for endobronchial intubation in
      children from birth to adolescence.

PMID- 15486003
TI  - Haemodynamic effects of remifentanil in children with and without intravenous
      atropine. An echocardiographic study.
AB  - BACKGROUND: Remifentanil is known to cause bradycardia and hypotension. We aimed
      to characterize the haemodynamic profile of remifentanil during sevoflurane
      anaesthesia in children with or without atropine. METHODS: Forty children who
      required elective surgery received inhalational induction of anaesthesia using 8%
      sevoflurane. They were allocated randomly to receive either atropine, 20 microg
      kg(-1) (atropine group) or Ringer's lactate (control group) after 10 min of
      steady-state 1 MAC sevoflurane anaesthesia (baseline). Three minutes later (T0),
      all children received remifentanil 1 microg kg(-1) injected over a 60 s period,
      followed by an infusion of 0.25 microg kg(-1) min(-1) for 10 min then 0.5 microg
      kg(-1) min(-1) for 10 min. Haemodynamic variables and echocardiographic data were
      determined at baseline, T0, T5, T10, T15 and T20 min. RESULTS: Remifentanil
      caused a significant decrease in heart rate compared with the T0 value, which was
      greater at T20 than T10 in the two groups: however, the values at T10 and T20
      were not significantly different from baseline in the atropine group. In
      comparison with T0, there was a significant fall in blood pressure in the two
      groups. Remifentanil caused a significant decrease in the cardiac index with or
      without atropine. Remifentanil did not cause variation in stroke volume (SV). In
      both groups, a significant increase in systemic vascular resistance occurred
      after administration of remifentanil. Contractility decreased significantly in
      the two groups, but this decrease remained moderate (between -2 and +2 sd).
      CONCLUSION: Remifentanil produced a fall in blood pressure and cardiac index,
      mainly as a result of a fall in heart rate. Although atropine was able to reduce
      the fall in heart rate, it did not completely prevent the reduction in cardiac
      index.

PMID- 15486004
TI  - Experience with the Arndt paediatric bronchial blocker.
AB  - Previously reported techniques for single lung ventilation in children have
      failed to provide consistent, single lung ventilation with relative ease and
      reliability. We report our experience with the use of a new device, the Arndt 5
      French (Fr) paediatric endobronchial blocker, for single lung ventilation in a
      series of 24 children. We were able to achieve single lung ventilation in 23 of
      the 24 patients (aged 2-16 yr). Placement required approximately 5-15 min.
      Attempts at placement were aborted in one patient who was unable to tolerate even
      short periods of apnoea because of lung pathology. Although it has some
      limitations, our experience suggests that the paediatric bronchial blocker can be
      used as a consistent, safe method of single lung ventilation in most young
      children.

PMID- 15486005
TI  - Effect of excessive environmental heat on core temperature in critically ill
      patients. An observational study during the 2003 European heat wave.
AB  - BACKGROUND: The primary goal of this study was to investigate the relation
      between the core temperature of critically ill patients and hot ambient
      temperatures during a heat wave. The second goal was to evaluate the impact of
      such a heat wave on the number of microbiological tests ordered. METHODS: During
      a heat wave, from August 3 to 22, 2003, we conducted an observational study in
      the surgical intensive care unit (ICU) of a French hospital that had no air
      conditioning at the time. The core temperature of 18 critically ill patients and
      36 health-care workers was measured with a non-contact, infrared tympanic
      membrane thermometer. The association between the core body temperature in
      infected and non-infected critically ill patients and the staff members, and the
      ambient temperature in the ICU was analysed using linear regression. The number
      of microbiological tests ordered was also recorded and compared with the same
      period in the previous year. RESULTS: The equation of the regression line for
      infected critically ill patients was: core temperature=33.5+0.16 x ambient
      temperature (R(2)=0.53; P<0.0001). The regression line was steeper than that for
      the non-infected patients (0.077; P<0.0001). The slopes of the regression lines
      for non-infected and control patients were similar (P=0.20). More blood cultures
      were carried out during the heat wave than at the same period during the year
      2002 (4.80 blood cultures per 1000 patient-days vs 2.47 per 1000 patient-days;
      P=0.0006). CONCLUSION: During a sustained high ambient temperature, hyperthermia
      can occur in critically ill infected patients and to a lesser extent in non
      infected patients and health-care workers. The number of blood cultures requested
      rises substantially, leading to increased costs. Installation of air-conditioning
      is therefore recommended.

PMID- 15486006
TI  - Allogeneic red blood cell transfusions: efficacy, risks, alternatives and
      indications.
AB  - Careful assessment of risks and benefits has to precede each decision on
      allogeneic red blood cell (RBC) transfusion. Currently, a number of key issues in
      transfusion medicine are highly controversial, most importantly the influence of
      different transfusion thresholds on clinical outcome. The aim of this article is
      to review current evidence on blood transfusions, to highlight 'hot topics' with
      respect to efficacy, outcome and risks, and to provide the reader with
      transfusion guidelines. In addition, a brief synopsis of transfusion alternatives
      will be given. Based on up-to-date information of current evidence, together with
      clinical knowledge and experience, the physician will be able to make transfusion
      decisions that bear the lowest risk for the patient.

PMID- 15486007
TI  - Thrombocytosis after trauma: incidence, aetiology, and clinical significance.
AB  - BACKGROUND: Our aim was to assess the occurrence, aetiology, and clinical
      significance of a platelet count greater than 600 x 10(3)/mm(3) in trauma
      patients. METHODS: All trauma patients admitted to the intensive care unit (ICU)
      during a 13-month period were prospectively studied. Platelet counts were
      performed daily. We recorded the patient's age, sex, nature of trauma, severity
      of illness scores, episodes of infections in the ICU, acute lung injury,
      bleeding, and thromboembolic events. Patients with thrombocytosis were also
      followed during their hospital stay and 1 month after hospital discharge.
      RESULTS: A total of 176 patients were included. Thrombocytosis developed in 36
      patients (20.4%) at a mean (sd) time of 14.0 (4.0) days and the platelet count
      normalized 35.0 (13.0) days after admission to the ICU. All patients with
      thrombocytosis had one or more possible predisposing conditions before the
      occurrence of thrombocytosis: nosocomial infection occurred in 30 patients (83%),
      acute lung injury in 17 (47%), bleeding in 27 (75%), and administration of
      cathecholamines in 24 (67%). Three venous thromboembolic complications occurred
      in the ICU (1.7%) and one during follow-up. Only one patient presented
      thrombocytosis at the time of diagnosis. Despite the fact that patients with
      thrombocytosis had a greater severity of illness, the ICU mortality was
      comparable among patients with and without thrombocytosis (8 vs 14%, P=0.34).
      CONCLUSIONS: Reactive thrombocytosis is a common finding after severe trauma and
      was found to be associated with a better survival than predicted by severity of
      illness score. Unless additional risk factors are present, reactive
      thrombocytosis is not associated with an increased risk of thromboembolic events.

PMID- 15486008
TI  - Volume kinetics of glucose 2.5% solution and insulin resistance after abdominal
      hysterectomy.
AB  - BACKGROUND: We hypothesized that volume kinetics can be used to predict the rate
      of infusion of glucose 2.5% solution required to yield any predetermined plasma
      glucose level and degree of plasma dilution during the postoperative period.
      METHODS: In 15 women, mean age 50 yr (range 37-63), 2 days after an abdominal
      hysterectomy, a volume kinetic analysis was performed on an i.v. infusion of 12.5
      ml kg(-1) ( approximately 900 ml) of glucose 2.5% given over 45 min. The insulin
      resistance was measured by a glucose clamp, and it was compared with daily
      bioimpedance analyses, which indicated the hydration of the intra/extracellular
      body fluid spaces. RESULTS: The clearance of glucose was 0.42 litre min(-1) (0.60
      litre min(-1) is normal) while the other five parameters in the kinetic model
      were similar to those obtained in healthy volunteers. Computer simulations
      indicated that in a 70-kg female, at steady state, the rate of infusion (ml min(
      1)) should be three times the allowed increase in plasma glucose (mmol litre(
      1)). To maintain a predetermined plasma dilution the corresponding rate factor
      was 160. The glucose uptake during clamping was 3.9 mg kg(-1) min(-1) (7.0 is
      normal), which, during the second day after hysterectomy, correlated with the
      dehydration of the intracellular space (r=0.77; P<0.002) and with the protein
      catabolism as indicated by the urinary excretion of 3-methylhistidine (r=-0.76,
      P<0.002). CONCLUSION: The anaesthetist can prescribe postoperative administration
      of glucose 2.5% to reach any desired plasma glucose level and dilution by using
      the two presented nomograms. Insulin resistance correlated with intracellular
      dehydration and protein catabolism.

PMID- 15486009
TI  - Preventing surgical deaths: critical care and intensive care outreach services in
      the postoperative period.

PMID- 15486011
TI  - Castrating the respiratory controller.

PMID- 15486010
TI  - Unconscious auditory priming during surgery with propofol and nitrous oxide
      anaesthesia: a replication.
AB  - BACKGROUND: Priming during anaesthesia has been hard to replicate and the
      conditions under which it occurs remain poorly understood. We replicated and
      extended a recent study to determine whether intraoperative priming during
      propofol and nitrous oxide anaesthesia is a reliable phenomenon, whether it
      occurs due to awareness during word presentation and whether it is suppressed by
      a dose of fentanyl at induction. METHODS: Words were played through headphones
      during surgery to 62 patients receiving propofol and nitrous oxide anaesthesia.
      Thirty-two patients received fentanyl 1.5 microg kg(-1) at induction and 30
      received no fentanyl. Neuromuscular blocking drugs were not used. Depth of
      anaesthesia was measured using the bispectral index (BIS). Anaesthetic variables
      were recorded at 1 min intervals during word presentation. On recovery, implicit
      and explicit memory were assessed using an auditory word-stem completion test and
      a yes-no word-recognition test, respectively. RESULTS: BIS, blood pressure, end
      tidal carbon dioxide and heart rate during word presentation did not differ
      between the study groups. The infusion rate of propofol and the patients'
      ventilatory frequency were significantly higher in the group not receiving
      fentanyl. No patient had unprompted explicit recall of surgery, although there
      was above-zero performance in six patients on the yes-no recognition task
      (P<0.05). There was no physiological evidence of awareness during anaesthesia
      (median mean-BIS=38 in the no-fentanyl group and 42 in the fentanyl group). There
      was evidence for priming (mean priming score=0.09, P<0.05 in the no-fentanyl
      study group; mean priming score=0.07, P<0.05 in the fentanyl group) even when
      patients with momentary light anaesthesia (maximum recorded BIS> or =60) and/or
      positive recognition scores were excluded from the analysis. CONCLUSIONS:
      Existing knowledge can be primed by information presented during propofol and
      nitrous oxide anaesthesia. This priming is evidence of unconscious information
      processing and not the result of moments of awareness.

PMID- 15486012
TI  - The effects of hypoxia on the modulation of human TREK-1 potassium channels.
AB  - Two-pore-domain potassium channels are a family of ion channels that are widely
      believed to play an important role in maintaining and regulating neuronal
      excitability. It has been shown that they can be modulated by an extraordinarily
      diverse range of endogenous and exogenous factors. One particular member of the
      family, TREK-1 (also known as KCNK2), is activated by increasing temperature,
      membrane stretch and internal acidosis, but is also sensitive to the presence of
      certain polyunsaturated fatty acids (such as arachidonic acid), neuroprotectants
      (such as riluzole) and volatile and gaseous general anaesthetics (such as
      halothane and nitrous oxide). It has recently been reported that TREK-1 channels
      are also affected by oxygen concentrations, and that at the levels of hypoxia
      that occur in the normal human brain, the channels greatly change their
      properties and, for example, lose their ability to be modulated by arachidonic
      acid and internal acidosis. These reports seriously challenge the idea that TREK
      1 is a target for general anaesthetics and neuroprotectants. However, in this
      report we show that TREK-1 is not oxygen sensitive, and its ability to be
      activated by anaesthetics, arachidonic acid and internal acidosis remains
      unaltered under conditions of hypoxia. We further show that the protocol used by
      previous workers to prepare hypoxic solutions of arachidonic acid results in the
      removal of the compound from solution.

PMID- 15486013
TI  - Chronic decentralization potentiates neurovascular transmission in the isolated
      rat tail artery, mimicking the effects of spinal transection.
AB  - Spinal cord transection produces a marked increase in the response of the
      isolated rat tail artery to sympathetic nerve stimulation, possibly as a result
      of a decrease in ongoing sympathetic activity. We have tested the effects of
      removing ongoing nerve activity on neurovascular transmission by cutting the
      preganglionic input to postganglionic neurones supplying the tail artery
      (decentralization). Isometric contractions to nerve stimulation were compared
      between decentralized arteries and those from age-matched and sham-operated
      controls. Nerve-evoked responses of decentralized arteries were much larger than
      those of control arteries at 2 and 7 weeks post operatively. The extent of
      blockade of nerve-evoked contraction by alpha-adrenoceptor antagonists prazosin
      (10 nM) or idazoxan (0.1 microM) was reduced. Decentralized arteries were
      transiently supersensitive to the alpha1-adrenoceptor agonist phenylephrine and
      the alpha2-adrenoceptor agonist clonidine; the unchanged sensitivity to
      methoxamine and phenylephrine after 2 weeks indicated no effect on the neuronal
      noradrenaline uptake transporter. Decentralized arteries were hypersensitive to
      alpha,beta methylene-ATP, but the P2-purinoceptor antagonist suramin (0.1 mM) did
      not reduce nerve-evoked contractions. Enlarged responses to 60 mM K+ after both 2
      and 7 weeks were correlated with the response of the arteries to nerve
      stimulation, suggesting that increased postjunctional reactivity contributes to
      the enhanced contraction. Comparison between data from decentralized arteries and
      our previous data from spinalized animals showed that the two lesions similarly
      potentiate nerve-evoked contractions and have similar but not identical
      postjunctional effects. The enhanced vascular responses following a reduction in
      tonic nerve activity may contribute to the hypertensive episodes of autonomic
      dysreflexia in spinally injured patients.

PMID- 15486014
TI  - Modulation of cytosolic and intra-sarcoplasmic reticulum calcium waves by
      calsequestrin in rat cardiac myocytes.
AB  - Waves of Ca2+-induced Ca2+ release occur in various cell types and are involved
      in the pathology of certain forms of cardiac arrhythmia. These arrhythmias
      include catecholaminergic polymorphic ventricular tachycardia (CPVT), certain
      cases of which are associated with mutations in the cardiac calsequestrin gene
      (CASQ2). To explore the mechanisms of Ca2+ wave generation and unravel the
      underlying causes of CPVT, we investigated the effects of adenoviral-mediated
      changes in CASQ2 protein levels on the properties of cytosolic and sarcoplasmic
      reticulum (SR) Ca2+ waves in permeabilized rat ventricular myocytes. The free
      [Ca2+] inside the sarcoplasmic reticulum ([Ca2+]SR) was monitored by fluo-5N
      entrapped into the SR, and cytosolic Ca2+ was imaged using fluo-3. Overexpression
      of CASQ2 resulted in significant increases in the amplitude of Ca2+ waves and
      interwave intervals, whereas reduced CASQ2 levels caused drastic reductions in
      the amplitude and period of Ca2+ waves. CASQ2 abundance had no impact on resting
      diastolic [Ca2+]SR or on the amplitude of the [Ca2+]SR depletion signal during
      the Ca2+ wave. However, the recovery dynamics of [Ca2+]SR following Ca2+ release
      were dramatically altered as the rate of [Ca2+]SR recovery increased
      approximately 3-fold in CASQ2-overexpressing myocytes and decreased to 30% of
      control in CASQ2-underexpressing myocytes. There was a direct linear relationship
      between Ca2+ wave period and the half-time of basal [Ca2+]SR recovery following
      Ca2+ release. Loading the SR with the low affinity exogenous Ca2+ buffer citrate
      exerted effects quantitatively similar to those observed on overexpressing CASQ2.
      We conclude that free intra-SR [Ca2+] is a critical determinant of cardiac Ca2+
      wave generation. Our data indicate that reduced intra-SR Ca2+ binding activity
      promotes the generation of Ca2+ waves by accelerating the dynamics of attaining a
      threshold free [Ca2+]SR required for Ca2+ wave initiation, potentially accounting
      for arrhythmogenesis in CPVT linked to mutations in CASQ2.

PMID- 15486015
TI  - Effects of angiotensin II on the pericyte-containing microvasculature of the rat
      retina.
AB  - The aim of this study was to identify the mechanisms by which angiotensin II
      alters the physiology of the pericyte-containing microvasculature of the retina.
      Despite evidence that this vasoactive signal regulates capillary perfusion by
      inducing abluminal pericytes to contract and thereby microvascular lumens to
      constrict, little is known about the events linking angiotensin exposure with
      pericyte contraction. Here, using microvessels freshly isolated from the adult
      rat retina, we monitored pericyte currents via perforated-patch pipettes,
      measured pericyte calcium levels with fura-2 and visualized pericyte contractions
      and lumen constrictions by time-lapse photography. We found that angiotensin
      activates nonspecific cation (NSC) and calcium-activated chloride channels; the
      opening of these channels induces a depolarization that is sufficient to activate
      the voltage-dependent calcium channels (VDCCs) expressed in the retinal
      microvasculature. Associated with these changes in ion channel activity,
      intracellular calcium levels rise, pericytes contract and microvascular lumens
      narrow. Our experiments revealed that an influx of calcium through the NSC
      channels is an essential step linking the activation of AT(1) angiotensin
      receptors with pericyte contraction. Although not required in order for
      angiotensin to induce pericytes to contract, calcium entry via VDCCs serves to
      enhance the contractile response of these cells. In addition to activating
      nonspecific cation, calcium-activated chloride and voltage-dependent calcium
      channels, angiotensin II also causes the functional uncoupling of pericytes from
      their microvascular neighbours. This inhibition of gap junction-mediated
      intercellular communication suggests a previously unappreciated complexity in the
      spatiotemporal dynamics of the microvascular response to angiotensin II.

PMID- 15486016
TI  - Differential involvement of oriens/pyramidale interneurones in hippocampal
      network oscillations in vitro.
AB  - Using whole-cell patch-clamp recordings in conjunction with post hoc anatomy we
      investigated the physiological properties of hippocampal stratum oriens and
      stratum pyramidale inhibitory interneurones, before and following the induction
      of pharmacologically evoked gamma frequency network oscillations. Prior to
      kainate-induced transient epochs of gamma activity, two distinct classes of
      oriens interneurones, oriens lacunosum-moleculare (O-LM) and trilaminar cells,
      showed prominent differences in their membrane and firing properties, as well as
      in the amplitude and kinetics of their excitatory postsynaptic events. In the
      active network both types of neurone received a phasic barrage of gamma frequency
      excitatory inputs but, due to their differential functional integration, showed
      clear differences in their output patterns. While O-LM cells fired intermittently
      at theta frequency, trilaminar interneurones discharged on every gamma cycle and
      showed a propensity to fire spike doublets. Two other classes of fast spiking
      interneurones, perisomatic targeting basket and bistratified cells, in the active
      network discharged predominantly single action potentials on every gamma cycle.
      Thus, within a locally excited network, O-LM cells are likely to provide a theta
      frequency patterned output to distal dendritic segments, whereas basket and
      bistratified cells are involved in the generation of locally synchronous gamma
      band oscillations. The anatomy and output profile of trilaminar cells suggest
      they are involved in the projection of locally generated gamma rhythms to distal
      sites. Therefore a division of labour appears to exist whereby different
      frequencies and spatiotemporal properties of hippocampal rhythms are mediated by
      different interneurone subtypes.

PMID- 15486017
TI  - Prolactin-releasing peptide affects gastric motor function in rat by modulating
      synaptic transmission in the dorsal vagal complex.
AB  - Prolactin-releasing peptide (PrRP) is a recently discovered neuropeptide
      implicated in the central control of feeding behaviour and autonomic homeostasis.
      PrRP-containing neurones and PrRP receptor mRNA are found in abundance in the
      caudal portion of the nucleus tractus solitarius (NTS), an area which together
      with the dorsal motor nucleus of the vagus (DMV) comprises an integrated
      structure, the dorsal vagal complex (DVC) that processes visceral afferent
      signals from and provides parasympathetic motor innervation to the
      gastrointestinal tract. In this study, microinjection experiments were conducted
      in vivo in combination with whole-cell recording from neurones in rat medullary
      slices to test the hypothesis that PrRP plays a role in the central control of
      gastric motor function, acting within the DVC to modulate the activity of
      preganglionic vagal motor neurones that supply the stomach. Microinjection of
      PrRP (0.2 pmol (20 nl)(-1)) into the DMV at the level of the area postrema (+0.2
      to +0.6 mm from the calamus scriptorius, CS) markedly stimulated gastric
      contractions and increased intragastric pressure (IGP). Conversely,
      administration of peptide into the DMV at sites caudal to the obex (0.0 to -0.3
      mm from the CS) decreased IGP and reduced phasic contractions. These effects
      occurred without change in mean arterial pressure and were abolished by
      ipsilateral vagotomy, indicating mediation via a vagal-dependent mechanism(s).
      The pattern of gastric motor responses evoked by PrRP mimicked that produced by
      administration of L-glutamate at the same sites, and both the effects of L
      glutamate and PrRP were abolished following local administration of NMDA and non
      NMDA-type glutamate receptor antagonists. On the other hand, microinjection of
      PrRP into the medial or comissural nucleus of the solitary tract (mNTS and
      comNTS, respectively) resulted in less robust changes in IGP in a smaller
      percentage of animals, accompanied by marked alterations in arterial pressure.
      Superfusion of brain slices with PrRP (100-300 nm) produced a small
      depolarization and increased spontaneous firing in 10 of 30 retrogradely labelled
      gastric-projecting DMV neurones. The excitatory effects were blocked by
      administration of TTX (2 mum) or specific glutamate receptor antagonists,
      indicating that they resulted from interactions of PrRP at a presynaptic site.
      Congruent with this, PrRP increased the amplitude of excitatory postsynaptic
      currents (EPSCs, 154 +/- 33%, 12 of 25 neurones) evoked by electrical stimulation
      in mNTS or comNTS. In addition, administration of PrRP decreased the paired-pulse
      ratio of EPSCs evoked by two identical stimuli delivered 100 ms apart (from 0.95
      +/- 0.08 to 0.71 +/- 0.11, P < 0.05), whereas it did not affect the amplitude of
      inward currents evoked by exogenous application of L-glutamate to the slice. The
      frequency, but not amplitude of spontaneous EPSCs and action potential
      independent miniature EPSCs was also increased by administration of PrRP,
      suggesting that the peptide was acting at least in part at receptors on
      presynaptic nerve terminals to enhance glutamatergic transmission. In recordings
      obtained from a separate group of slices, we did not observe any direct effects
      of PrRP on spontaneous discharge or postsynaptic excitability in either mNTS or
      comNTS neurones (n = 31). These data indicate that PrRP may act within the DVC to
      regulate gastric motor function by modulating the efficacy of conventional
      excitatory synaptic inputs from the NTS onto gastric-projecting vagal motor
      neurones.

PMID- 15486018
TI  - Histidine-stimulated divalent metal uptake in human erythrocytes and in the
      erythroleukaemic cell line HEL.92.1.7.
AB  - The uptake of 65Zn by human erythrocytes was investigated in the presence of high
      (40 mM) and low (5 mM) concentrations of histidine and 0-500 microM cobalt,
      nickel, manganese and zinc. Varying concentrations of metal mono- and bis
      histidine complexes will be formed and the inhibition of 65Zn uptake could be
      correlated with the calculated complex concentrations to investigate competition
      between metals. For each metal, the calculated concentrations of bis-histidine
      complex giving 50% inhibition of 65Zn uptake were similar at both 5 mM and 40 mM
      histidine. Manganese-bis-histidine appeared to have a much higher affinity for
      the binding site than the other metal-bis-histidine complexes, which had similar
      affinities to each other. Studies of the inhibition of histidine-stimulated 54Mn
      uptake by the addition of manganese confirmed that manganese-bis-histidine does
      act as a substrate for the transporter in a similar fashion to the other metals
      studied. In addition, human erythroleukaemic cells (HEL cells) were used as a
      model for erythroid precursor cells. L-histidine, but not D-histidine, stimulated
      65Zn uptake in a saturable fashion. The other metals competed with zinc in a
      similar manner to that seen in erythrocytes, and the affinity for manganese-bis
      histidine was much greater than for the bis-histidine complexes of the other
      three metals. Both the capacity for metal transport per cell, and the affinity of
      the transporter for the metal-bis-histidine complexes, were much greater in the
      HEL cells than in the erythrocyte. It is suggested that histidine-stimulated
      metal transport may play a role in the supply of metals to maturing erythroid
      cells.

PMID- 15486019
TI  - Advanced vaginal opening and precocious activation of the reproductive axis by
      KiSS-1 peptide, the endogenous ligand of GPR54.
AB  - The awakening of the gonadotrophic axis at puberty is the end-point of a complex
      cascade of sex developmental events that leads to the attainment of reproductive
      capacity. Recently, loss-of-function mutations of the gene encoding GPR54, the
      putative receptor for the KiSS-1-derived peptide metastin, have been linked to
      hypogonadotrophic hypogonadism, both in rodents and humans. However, the actual
      role of the KiSS-1/GPR54 system in the timing of puberty onset remains
      unexplored. We report herein that chronic central administration of KiSS-1
      peptide to immature female rats induced the precocious activation of the
      gonadotrophic axis, as estimated by advanced vaginal opening, elevated uterus
      weight, and increased serum levels of luteinizing hormone (LH) and oestrogen. The
      central effect of KiSS-1 upon LH release appeared to be mediated via the
      hypothalamic LH-releasing hormone. In contrast, despite the well-documented
      permissive role of body fat stores and the adipocyte-derived hormone leptin in
      puberty maturation, acute activation of the gonadotrophic axis by KiSS-1 was
      persistently observed in pubertal animals under food deprivation, after central
      immunoneutralization of leptin, and in a model of leptin resistance. Overall, the
      present results, together with our recent data on maximum expression of KiSS-1
      and GPR54 genes in the hypothalamus at puberty, provide novel evidence for a role
      of the KiSS-1 system as a downstream element in the hypothalamic network
      triggering the onset of puberty.

PMID- 15486020
TI  - Histamine innervation and activation of septohippocampal GABAergic neurones:
      involvement of local ACh release.
AB  - Recent studies indicate that the histaminergic system, which is critical for
      wakefulness, also influences learning and memory by interacting with cholinergic
      systems in the brain. Histamine-containing neurones of the tuberomammillary
      nucleus densely innervate the cholinergic and GABAergic nucleus of the medial
      septum/diagonal band of Broca (MSDB) which projects to the hippocampus and
      sustains hippocampal theta rhythm and associated learning and memory functions.
      Here we demonstrate that histamine, acting via H(1) and/or H(2) receptor
      subtypes, utilizes direct and indirect mechanisms to excite septohippocampal GABA
      type neurones in a reversible, reproducible and concentration-dependent manner.
      The indirect mechanism involves local ACh release, is potentiated by
      acetylcholinesterase inhibitors and blocked by atropine methylbromide and 4-DAMP
      mustard, an M(3) muscarinic receptor selective antagonist. This indirect effect,
      presumably, results from a direct histamine-induced activation of
      septohippocampal cholinergic neurones and a subsequent indirect activation of the
      septohippocampal GABAergic neurones. In double-immunolabelling studies, histamine
      fibres were found in the vicinity of both septohippocampal cholinergic and
      GABAergic cell types. These findings have significance for Alzheimer's disease
      and other neurodegenerative disorders involving a loss of septohippocampal
      cholinergic neurones as such a loss would also obtund histamine effects on
      septohippocampal cholinergic and GABAergic functions and further compromise
      hippocampal arousal and associated cognitive functions.

PMID- 15486021
TI  - Charged residue alterations in the inner-core domain and carboxy-terminus of
      alpha-tropomyosin differentially affect mouse cardiac muscle contractility.
AB  - Two important charge differences between the alpha- and beta-tropomyosin (TM)
      isoforms are the exchange of a serine residue in the inner-core region at
      position 229, and a histidine residue at the carboxy-terminal end at position
      276, with glutamic acid and asparagine, respectively. We have recently shown that
      altering these two residues in alpha-TM to their beta-TM counterparts in
      transgenic (TG) mouse hearts causes a depression in both +dP/dt and -dP/dt and a
      decrease in calcium sensitivity. In this study, we address whether independent
      charge changes at these two residues in alpha-TM modulate cardiac function
      differentially. To test this hypothesis we generated two TG lines: alpha
      TMSer229Glu and alpha-TMHis276Asn. Molecular analyses show that 98% of native
      alpha-TM is replaced by mutated protein in alpha-TM229 hearts whereas alpha-TM276
      hearts show 82% replacement with the mutated protein. Isolated working heart data
      show that alpha-TM229 TG hearts exhibit a significant decrease in both +dP/dt
      (7%) and -dP/dt (8%) compared with nontransgenics (NTGs) and time to peak
      pressure (TPP) is also reduced in alpha-TM229 hearts. alpha-TM276 hearts show a
      decrease only in -dP/dt (14%) and TPP is increased. pCa(2+)-tension relationships
      in skinned fibre preparations indicate decreased calcium sensitivity in alpha
      TM229 but no change in alpha-TM276 preparations. Force-[Ca(2+)](IC) measurements
      from intact papillary fibres indicate that alpha-TM276 fibres produce more force
      per given [Ca(2+)](IC) when compared to NTG fibres, while alpha-TM229 fibres
      produce less force per given [Ca(2+)](IC). These data demonstrate that changing
      charged residues at either the inner-core domain or the carboxyl end of TM alters
      sarcomeric performance differently, suggesting that the function of TM is
      compartmentalized along its length.

PMID- 15486022
TI  - The influence of fatigue on damage from eccentric contractions in the
      gastrocnemius muscle of the cat.
AB  - Eccentric exercise is unique in that it can lead to muscle damage and soreness.
      Concentric exercise is not accompanied by evidence of damage. There are reports
      in the literature that muscle fatigue is a factor determining the amount of
      damage from eccentric exercise. Our theory for the damage process predicts that
      susceptibility for damage is independent of fatigue. Experiments were carried out
      to test this prediction as well as to seek other evidence in support of our
      theory. Comparisons were made between the effects of eccentric and concentric
      contractions. The nerve supply to the medial gastrocnemius muscle of the
      anaesthetized cat was divided into three equal portions in terms of the tension
      they generated. In the first experiment a muscle portion was fatigued by giving
      it 200 shortening contractions over 12 mm at a shortening speed of 50 mm s(-1).
      This led to a mean fall in isometric tension (37 +/- 4%) without a significant
      shift in the optimum length for peak active tension. Giving the fatigued muscle
      10 eccentric contractions, active stretches over 6 mm at 50 mm s(-1), beginning
      from the muscle's optimum length led to a further fall in tension (11% +/- 7%)
      and a significant shift in optimum length (3.7 mm +/- 0.6 mm) in the direction of
      longer muscle lengths. The shift in optimum was taken as an indicator of muscle
      damage. This shift was not significantly different from that seen after eccentric
      contractions carried out on an unfatigued muscle. After a series of eccentric or
      concentric contractions, tension at the end of a ramp shortening of 6 mm at 10 mm
      s(-1) fell more than isometric tension, and by near equal amounts for the two
      kinds of contractions. In an unfatigued muscle, if tension was altered by
      changing the rate of stimulation, the fall in shortening tension was greater than
      after either concentric or eccentric contractions. These observations were seen
      to be consistent with predictions of the proposed mechanism for the damage
      process.

PMID- 15486023
TI  - Stabilization of TRAIL, an all-beta-sheet multimeric protein, using computational
      redesign.
AB  - Protein thermal stability is important for therapeutic proteins, both influencing
      the pharmacokinetic and pharmacodynamic properties and for stability during
      production and shelf-life of the final product. In this paper we show the
      redesign of a therapeutically interesting trimeric all-beta-sheet protein, the
      cytokine TRAIL (tumor necrosis factor-related apoptosis-inducing ligand),
      yielding variants with improved thermal stability. A combination of tumor
      necrosis factor (TNF) ligand family alignment information and the computational
      design algorithm PERLA was used to propose several mutants with improved thermal
      stability. The design was focused on non-conserved residues only, thus reducing
      the use of computational resources. Several of the proposed mutants showed a
      significant increase in thermal stability as experimentally monitored by far-UV
      circular dichroism thermal denaturation. Stabilization of the biologically active
      trimer was achieved by monomer subunit or monomer-monomer interface
      modifications. A double mutant showed an increase in apparent T(m) of 8 degrees C
      in comparison with wild-type TRAIL and remained biologically active after
      incubation at 73 degrees C for 1 h. To our knowledge, this is the first study
      that improves the stability of a large multimeric beta-sheet protein structure by
      computational redesign. A similar approach can be used to alter the
      characteristics of other multimeric proteins, including other TNF ligand family
      members.

PMID- 15486024
TI  - Design, synthesis and analysis of novel bicyclic and bifunctional protease
      inhibitors.
AB  - Two novel synthetic inhibitors were designed to combine the advantageous
      properties of Bowman Birk inhibitor (BBI) and sunflower trypsin inhibitor-1 (SFTI
      1). As is the case for BBI, the novel inhibitors have two active sites that give
      dual independent protease inhibition. However, they also possess a small bicyclic
      structure, reminiscent of the single-site SFTI-1. It is found that the synthetic
      inhibitors retain the potent inhibitory properties of the parent structures; they
      are also found to be relatively resistant to proteolysis. Their inhibition
      properties and a comparison of their stability to proteolysis relative to SFTI-1
      are described. It is found that the new inhibitors do indeed allow bifunctional
      inhibition, although, unlike BBI, the small size of the inhibitor prevents the
      simultaneous inhibition of two proteases at the same time.

PMID- 15486025
TI  - Immunoassay to measure ataxia-telangiectasia mutated protein in cellular lysates.
AB  - BACKGROUND: Ataxia-telangiectasia (A-T) is a neurologic disorder caused by
      mutations in the ataxia-telangiectasia mutated (ATM) gene. A clinical diagnosis
      of A-T is confirmed by radiosensitivity testing and immunoblotting for ATM
      protein. Because both of these tests have long turnaround times (> or =3 months),
      we developed a rapid immunoassay to measure ATM protein and determined its
      sensitivity and specificity for diagnosing A-T. METHODS: Recombinant ATM protein
      was used for standardization. Lysates of lymphoblastoid cell lines (LCLs) and
      peripheral blood mononuclear cells (PBMCs) from A-T patients, controls, and A-T
      heterozygotes were tested for ATM protein by immunoassay. RESULTS: Between-run
      imprecision (CV) was < or =13%. Nuclear lysates from control LCLs and PBMCs had
      ATM protein concentrations of 49-610 microg/L and 48-943 microg/L, respectively.
      ATM protein was not detectable in LCL nuclear lysates from 18 of 21 A-T patients.
      The three remaining A-T patients had trace amounts of ATM protein, which was
      confirmed on immuoblots. ATM protein was also detectable in whole-cell lysates
      from 4 x 10(6) cells at concentrations of 64-463 microg/L and 42-444 microg/L for
      control LCLs and PBMCs, respectively. A-T heterozygotes had ATM protein
      concentrations of 52-98 microg/L. ATM protein was stable in PBMCs stored for 1
      month at -70 degrees C, but rapidly decreased after 1 day in unprocessed blood.
      CONCLUSIONS: This ATM protein immunoassay can be used to confirm a diagnosis of A
      T in 2 days on small numbers of PBMCs and can potentially identify A-T carriers
      and individuals at increased risk for cancer.

PMID- 15486026
TI  - Quantitative, highly sensitive liquid chromatography-tandem mass spectrometry
      method for detection of synthetic corticosteroids.
AB  - BACKGROUND: Measurements of serum or urine concentrations of synthetic
      glucocorticoids are useful for assessing suspected iatrogenic hypothalamic
      pituitary-adrenal axis suppression and Cushing syndrome. We have developed a
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the
      simultaneous quantitative analysis of beclomethasone dipropionate, betamethasone,
      budesonide, dexamethasone, fludrocortisone, flunisolide, fluorometholone,
      fluticasone propionate, megestrol acetate, methylprednisolone, prednisolone,
      prednisone, triamcinolone, and triamcinolone acetonide. METHODS: Stable isotopes
      of cortisol-9,11,12,12-d(4) and triamcinolone-d(1) acetonide-d(6) were added as
      internal standards to calibrators, controls, and unknown samples. After
      acetonitrile precipitation, these samples were extracted with methylene chloride,
      and the extracts were washed and dried. Reconstituted extract (15 muL) was
      injected on a reversed-phase column and analyzed by LC-MS/MS in positive-ion
      mode. Assay precision, accuracy, linearity, and sample stability were determined
      by use of enriched samples. Clinical validation included analysis of 8 serum and
      20 urine samples from patients with undetectable cortisol concentrations and
      analysis of different types of tablets. RESULTS: Functional assay sensitivity was
      as low as 0.6-1.6 nmol/L for all compounds except for triamcinolone (7.6 nmol/L).
      Interassay CVs were 3.0-20% for concentrations of 0.6-364 nmol/L for all
      analytes. Recoveries of all analytes (except triamcinolone in serum) were 82-138%
      at 19.2-693 nmol/L. All but one of the serum and urine samples from patients who
      were tested because of suppressed cortisol concentrations contained at least one
      synthetic steroid. Tablet analysis recovered 75% of the synthetic steroids in
      suspected drugs. CONCLUSIONS: LC-MS/MS allows simultaneous quantitative detection
      of various synthetic steroids in serum, plasma, urine, and tablets. This provides
      a valuable tool for evaluating the clinical effects of topical and systemic
      synthetic corticosteroids.

PMID- 15486027
TI  - Interaction between endothelial heme oxygenase-2 and endothelin-1 in altered
      aortic reactivity after hypoxia in rats.
AB  - The aim of this study was to determine whether increased expression of heme
      oxygenase (HO) contributes to impairment of aortic contractile responses after
      hypoxia through effects on reactivity to endothelin-1 (ET-1). Thoracic aortas
      from normoxic rats and rats exposed to hypoxia (10% O2) for 16 or 48 h were
      mounted in organ bath myographs for contractile studies, fixed in
      paraformaldehyde, or frozen in liquid nitrogen for protein extraction. In rings
      from normoxic rats, the HO inhibitor tin protoporphyrin IX (SnPP IX, 10 microM)
      did not alter the response to phenylephrine or ET-1. In rings from rats exposed
      to 16-h hypoxia, maximum tension generated in response to these agonists was
      higher in endothelium-intact but not -denuded rings in the presence of SnPP IX.
      In rings from rats exposed to 48-h hypoxia SnPP IX increased contraction in
      endothelium-intact but not -denuded rings. In endothelium-intact aortic rings
      from rats exposed to 16-h hypoxia incubated with endothelin A receptor-specific
      antagonist BQ-123 (10(-7) M), SnPP IX did not alter phenylephrine-induced
      contraction. Aortic ET-1 protein levels, measured by radioimmunoassay, were
      increased in rats exposed to hypoxia for 16 and 48 h. Western blotting showed
      that HO-1 and HO-2 protein were increased after 16 h of hypoxia and returned to
      near-control levels after 48 h. Increase in HO-1 protein was detected in
      endothelium-intact and -denuded rings. Removal of endothelium abolished the
      increase in HO-2 immunoreactivity. Immunohistochemistry localized expression of
      HO-1 protein to vascular smooth muscle, whereas HO-2 was only detected in
      endothelium. HO-2 is expressed by aortic endothelial cells early during hypoxic
      exposure and impairs ET-1-mediated potentiation of contraction to alpha
      adrenoceptor stimulation.

PMID- 15486028
TI  - Myocardium tolerant to an adenosine-dependent ischemic preconditioning stimulus
      can still be protected by stimuli that employ alternative signaling pathways.
AB  - Clinical studies on cardioprotection by preinfarct angina are ambiguous, which
      may involve development of tolerance to repeated episodes of ischemia. Not all
      preconditioning stimuli use identical signaling pathways, and because patients
      likely experience varying numbers of episodes of preinfarct angina of different
      degrees and durations, it is important to know whether myocardium tolerant to a
      particular preconditioning stimulus can still be protected by stimuli employing
      alternative signaling pathways. We tested the hypothesis that development of
      tolerance to a particular stimulus does not affect cardioprotection by stimuli
      that employ different signaling pathways. Anesthetized rats underwent classical,
      remote or pharmacological preconditioning. Infarct size (IS), produced by a 60
      min coronary artery occlusion (CAO), was determined after 120 min of reperfusion.
      Preconditioning by two 15-min periods of CAO (2CAO15, an adenosine-dependent
      stimulus) limited IS from 69 +/- 2% to 37 +/- 6%, but when 2CAO15 was preceded by
      4CAO15, protection by 2CAO15 was absent (IS = 68 +/- 1%). This development of
      tolerance coincided with a loss of cardiac interstitial adenosine release,
      whereas two 15-min infusions of adenosine (200 microg/min i.v.) still elicited
      cardioprotection (IS = 40 +/- 4%). Furthermore, cardioprotection was produced
      when 4CAO15 was followed by the adenosine-independent stimulus 3CAO3 (IS = 50 +/-
      8%) or the remote preconditioning stimulus of two 15-min periods of mesenteric
      artery occlusion (IS = 49 +/- 6%). In conclusion, development of tolerance to
      cardioprotection by an adenosine-dependent preconditioning stimulus still allows
      protection by pharmacological or ischemic stimuli intervention employing
      different signaling pathways.

PMID- 15486029
TI  - Abnormal cardiac wall motion and early matrix metalloproteinase activity.
AB  - Activation of matrix metalloproteinases (MMPs) in the heart is known to
      facilitate cardiac remodeling and progression to failure. We hypothesized that
      regional dyskinetic wall motion of the left ventricle would stimulate activation
      of MMPs. Abnormal wall motion at a target site on the anterior lateral wall of
      the left ventricle was induced by pacing atrial and ventricular sites of five
      open-chest anesthetized dogs. Changes in shortening at the left ventricular (LV)
      pacing site and at a remote site at the anterior base of the left ventricle were
      monitored with piezoelectric crystals. Simultaneous atrial and ventricular pacing
      resulted in abnormal motion at the LV pacing site, yielding early shortening and
      late systolic lengthening, whereas the shortening pattern at the remote site
      remained unaffected. Assessment of global myocardial MMP activity showed a
      sevenfold increase in substrate cleavage (P < 0.02) at the LV pacing site
      relative to the remote site. Gelatin zymography revealed increases in 92-kDa MMP
      9 activity and 86-kDa MMP-9 activity at the LV pacing site relative to the remote
      site, whereas MMP-2 activity was unaffected. Abnormal wall motion was associated
      with increases in collagen degradation (approximately 2-fold; P < 0.03), plasmin
      activity (approximately 1.5-fold; P < 0.05), nitrotyrosine levels (approximately
      20-fold; P = 0.05), and inflammatory infiltrate (approximately 2-fold; P < 0.02)
      relative to the remote site. Results indicate that regional dyskinesis induced by
      epicardial activation is sufficient to stimulate significant MMP activity in the
      heart, suggesting that abnormal wall motion is a stimulus for MMP activation.

PMID- 15486030
TI  - Salt-induced ANG II suppression impairs the response of cerebral artery smooth
      muscle cells to prostacyclin.
AB  - Recent studies have demonstrated that cerebral arteries from rats fed a high-salt
      (HS) diet exhibit impaired vasodilation and altered electrophysiological response
      to reduction in PO2. The present study examined whether an increase in salt
      intake alters the response of vascular smooth muscle cells (VSMC) to
      prostacyclin, a crucial mediator of hypoxic dilation in cerebral arteries. VSMC
      were isolated from cerebral arteries of male Sprague-Dawley rats maintained on an
      HS (4% NaCl) or a low-salt diet (0.4% NaCl) for 3 days. The stable prostacyclin
      analog iloprost (10 ng/ml) inhibited serotonin (0.1-10 microM)-induced
      contractions and the increase in intracellular Ca2+ concentration ([Ca2+]i) in
      VSMC isolated from arteries of animals fed the low-salt diet. In contrast,
      iloprost had no effect on serotonin-induced contractions and increases in [Ca2+]i
      in VSMC isolated from arteries of rats fed the HS diet. Preventing the fall in
      ANG in rats fed the HS diet by infusion of a low dose of ANG II (5 ng.kg(-1).min(
      1) i.v.) restored the inhibitory effect of iloprost on serotonin-induced
      contractions and increases in [Ca2+]i in VSMC from animals fed the HS diet. These
      effects were reversed by AT1 receptor blockade with losartan. These results
      indicate that ANG II suppression secondary to elevated dietary salt intake
      impairs vascular relaxation and Ca2+ regulation by prostacyclin.

PMID- 15486031
TI  - Regulation of atrial contraction by PKA and PKC during development and regression
      of eccentric cardiac hypertrophy.
AB  - ANG II plays a major role in development of cardiac hypertrophy through its AT1
      receptor subtype, whereas angiotensin-converting enzyme (ACE) inhibitors are
      effective in reversing effects of ANG II on the heart. The objective of this
      study was to investigate the role of PKA and PKC in the contractile response of
      atrial tissue during development and ACE inhibitor-induced regression of
      eccentric hypertrophy induced by aortocaval shunt. At 1 wk after surgery, sham
      and shunt rats were divided into captopril-treated and untreated groups for 2 wk.
      Then isometric contraction was assessed by electrical stimulation of isolated rat
      left atrial preparations superfused with Tyrode solution in the presence or
      absence of specific inhibitors KT-5720 (for PKA) and Ro-32-0432 (for PKC) and
      high Ca2+. Peak tension developed was greater in shunt than in sham hearts.
      However, when expressed relative to tissue mass, hypertrophied muscle showed
      weaker contraction than muscle from sham rats. In sham rats, peak tension
      developed was more affected by PKC than by PKA inhibition, whereas this
      differential effect was reduced in the hypertrophied heart. Treatment of shunt
      rats with captopril regressed left atrial hypertrophy by 67% and restored PKC-PKA
      differential responsiveness toward sham levels. In the hypertrophied left atria,
      there was an increase in the velocity of contraction and relaxation that was not
      evident when expressed in specific relative terms. Treatment with ACE inhibitor
      increased the specific velocity of contraction, as well as its PKC sensitivity,
      in shunt rats. We conclude that ACE inhibition during eccentric cardiac
      hypertrophy produces a negative trophic and a positive inotropic effect, mainly
      through a PKC-dependent mechanism.

PMID- 15486032
TI  - MRI-determined left ventricular "crescent effect": a consequence of the slight
      deviation of contents of the pericardial sack from the constant-volume state.
AB  - During one cardiac cycle, the volume encompassed by the pericardial sack in
      healthy subjects remains nearly constant, with a transient +/-5% decrease in
      volume at end systole. This "constant-volume" attribute defines a constraint that
      the longitudinal versus radial pericardial contour dimension relationship must
      obey. Using cardiac MRI, we determined the extent to which the constant-volume
      attribute is valid from four-chamber slices (two-dimensional) compared with three
      dimensional volumetric data. We also compared the relative percentage of
      longitudinal versus radial (short-axis) change in cross-sectional area
      (dimension) of the pericardial contour, thereby assessing the fate of the +/-5%
      end-systolic volume decrease. We analyzed images from 10 normal volunteers and 1
      subject with congenital absence of the pericardium, obtained using a 1.5-T MR
      scanner. Short-axis cine loop stacks covering the entire heart were acquired, as
      were single four-chamber cine loops. In the short-axis and four-chamber slices,
      relative to midventricular end-diastolic location, end-systolic pericardial (left
      ventricular epicardial) displacement was observed to be radial and maximized at
      end systole. Longitudinal (apex to mediastinum) pericardial contour dimension
      change and pericardial area change on the four-chamber slice were negligible
      throughout the cardiac cycle. We conclude that the +/-5% end-systolic decrease in
      the volume encompassed by the pericardial sack is primarily accounted for by a
      "crescent effect" on short-axis views, manifesting as a nonisotropic radial
      diminution of the pericardial/epicardial contour of the left ventricle. This
      systolic drop in cardiac volume occurs primarily at the ventricular level and is
      made up during the subsequent diastole when blood crosses the pericardium in the
      pulmonary venous Doppler D wave during early rapid left ventricular filling.

PMID- 15486033
TI  - Hypertension attenuates cell-to-cell communication in hamster retractor muscle
      feed arteries.
AB  - This study examined whether hypertension attenuated cell-to-cell communication in
      skeletal muscle resistance arteries. Briefly, arteries feeding the retractor
      muscle of normotensive and hypertensive hamsters were cannulated, pressurized,
      and superfused with a physiological saline solution. Cell-to-cell communication
      was functionally assessed by application of vasoactive stimuli (via micropipette)
      to a small portion of a feed artery while diameter at sites distal to the point
      of agent application was monitored. In keeping with past observations, discrete
      application of a smooth muscle depolarizing agent (phenylephrine or KCl) elicited
      a localized vasoconstriction that conducted poorly along feed arteries from
      normotensive hamsters. In contrast, acetylcholine, an agent known to
      hyperpolarize endothelial cells, elicited a vasodilation in normotensive feed
      arteries that conducted with little decay. Whereas smooth muscle depolarizing
      agents continued to elicit a localized response, conduction of endothelium
      dependent vasodilation was attenuated in hypertensive hamsters. This decrease
      occurred in the absence of changes in vessel reactivity to intravascular pressure
      or to global application of phenylephrine, U-46619, or acetylcholine. We propose,
      on the basis of these physiological observations, quantitative mRNA measurements
      of connexins 37, 40, 43, and 45, and analysis of the literature, that an increase
      in endothelial-to-endothelial or smooth muscle-to-endothelial coupling resistance
      is likely responsible for hypertension-induced impairment in vascular
      communication. We hypothesize that this attenuation could contribute to the rise
      in total peripheral resistance characteristically observed in hypertension.

PMID- 15486034
TI  - Regional timing of myocardial shortening is related to prestretch from atrial
      contraction: assessment by high temporal resolution MRI tagging in humans.
AB  - Earlier studies have shown substantial nonuniformity in normal left ventricular
      (LV) myocardial function concerning both the degree of shortening and timing of
      shortening. We hypothesized that nonuniform LV function may be related to
      nonuniform prestretch induced by atrial contraction. Eleven healthy human
      subjects were studied using MRI myocardial tagging and strain analysis. The
      amount of circumferential prestretch was assessed in 30 LV segments. Prestretch
      was defined as the difference in strain between end diastole (at ECG R wave) and
      diastasis. Furthermore, both the degree of shortening (quantified as peak
      circumferential shortening, peak systolic shortening rate, and amount of
      postsystolic shortening) and timing of shortening (quantified as the onset time
      of shortening and time to peak shortening) were assessed. LV prestretch was found
      to be nonuniform, with the highest values in the lateral wall. The amount of
      segmental prestretch correlated significantly with peak shortening (r = 0.79),
      peak shortening rate (r = 0.50), amount of postsystolic shortening (r = 0.67),
      onset time of shortening (r = -0.57), and time to peak shortening (r = 0.71) (P <
      0.001 for each of these relations). These relations may be explained by regional
      differences in wall stress or by a regional Frank-Starling effect. The
      correlation between timing of shortening and prestretch demonstrates that
      mechanical timing is not determined by electrical phenomena alone. In conclusion,
      regional variation in LV function correlates with the nonuniform prestretch from
      atrial contraction.

PMID- 15486035
TI  - Forearm neurovascular responses during mental stress and vestibular activation.
AB  - Autonomic responses may underlie associations among anxiety, vestibular
      dysfunction, and unexplained syncope. Mental stress (MS), an anxiety-inducing
      stimulus, causes forearm vasodilation, whereas the vestibulosympathetic reflex
      (VSR) causes forearm vasoconstriction. The purpose of this study was to examine
      the combined effects of mental and vestibular stimulation on neurovascular
      control in the forearm. Heart rate, arterial pressure (Finapres), and forearm
      blood flow (Doppler) were measured in 10 healthy volunteers in the prone position
      during 1) head-down rotation (HDR), 2) MS (mental arithmetic), and 3) HDR + MS.
      Forearm vascular resistance (FVR) increased during HDR (from 232 +/- 40 to 319 +/
      53 units) and decreased during MS (from 260 +/- 57 to 154 +/- 22 units). During
      HDR + MS, FVR did not change [change (Delta) = -31 +/- 50 units] and was not
      significantly different from the algebraic sum of each trial performed alone
      (Delta = -20 +/- 42 units). Arm muscle sympathetic nerve activity (MSNA;
      microneurography) was measured in seven additional subjects. MSNA increased
      during HDR (from 13 +/- 2 to 17 +/- 2 bursts/min) and HDR + MS (from 11 +/- 2 to
      16 +/- 2 bursts/min). Increases in MSNA during HDR + MS (Delta = 5 +/- 2
      bursts/min) were not different from the algebraic sum of each trial performed
      alone (Delta = 6 +/- 2 bursts/min). We conclude that an additive neurovascular
      interaction exists between MS and the VSR in the forearm. Activation of the VSR
      prevented forearm vasodilation during MS, suggesting that activation of the VSR
      may help protect against stress-induced syncope.

PMID- 15486036
TI  - Effect of simvastatin on left ventricular mass in hypercholesterolemic rabbits.
AB  - Epidemiological studies showed that hypercholesterolemia is associated with
      higher left ventricular mass. Endothelin signaling is activated in hyperlipidemic
      animals and may contribute to progressive ventricular hypertrophy. Simvastatin
      has been shown to inhibit endothelin-1. However, the behavior of simvastatin on
      ventricular hypertrophy in hyperlipidemic animals is not well understood. In this
      study, we evaluated the hemodynamic, biochemical, and morphological responses to
      simvastatin in cholesterol-fed (1%) rabbits. The left ventricular weight
      increased 8 wk after cholesterol feeding compared with that in
      normocholesterolemic rabbits. Simvastatin at a clinical therapeutic dose (1.2 mg
      x kg(-1) x day(-1)) significantly decreased left ventricular weight by 14% and
      left ventricular myocyte sizes by 14% as isolated by enzymatic dissociation.
      Hypercholesterolemia upregulated ventricular preproendothelin-1 mRNA as assessed
      by real-time quantitative RT-PCR and elevated production of cardiac endothelin-1
      concentration. The increased endothelin-1 responses can be inhibited after
      simvastatin administration. Left ventricular mass indexed by body weight
      positively correlated with tissue endothelin-1 levels (P = 0.0003). In
      Langendorff-perfused rabbit hearts, hyperlipidemia led to significant QT
      prolongation compared with normocholesterolemia, which can be reversed by
      administering simvastatin. In contrast, simvastatin-induced beneficial effects
      were reversed by the addition of mevalonate. The addition of bosentan, a
      nonspecific endothelin receptor blocker, improved the response in
      hypercholesterolemic rabbits and did not have additional beneficial effects in
      simvastatin-treated rabbits. The results of the present study suggest that the
      antihypertropic and electrocardiographic effects of simvastatin at a clinical
      therapeutic dose are mediated through inhibition of tissue endothelin-1
      expression, which is linked to mevalonate metabolism, and result in an
      amelioration of cardiomyocyte hypertrophy development by an atherogenic diet.

PMID- 15486037
TI  - Engineering of fibrin-based functional and implantable small-diameter blood
      vessels.
AB  - We engineered implantable small-diameter blood vessels based on ovine smooth
      muscle and endothelial cells embedded in fibrin gels. Cylindrical tissue
      constructs remodeled the fibrin matrix and exhibited considerable reactivity in
      response to receptor- and nonreceptor-mediated vasoconstrictors and dilators.
      Aprotinin, a protease inhibitor of fibrinolysis, was added at varying
      concentrations and affected the development and functionality of tissue
      engineered blood vessels (TEVs) in a concentration-dependent manner.
      Interestingly, at moderate concentrations, aprotinin increased mechanical
      strength but decreased vascular reactivity, indicating a possible relationship
      between matrix degradation/remodeling, vasoreactivity, and mechanical properties.
      TEVs developed considerable mechanical strength to withstand interpositional
      implantation in jugular veins of lambs. Implanted TEVs integrated well with the
      native vessel and demonstrated patency and similar blood flow rates as the native
      vessels. At 15 wk postimplantation, TEVs exhibited remarkable matrix remodeling
      with production of collagen and elastin fibers and orientation of smooth muscle
      cells perpendicular to the direction of blood flow. Implanted vessels gained
      significant mechanical strength and reactivity that were comparable to those of
      native veins. Our work demonstrates that fibrin-based TEVs hold significant
      promise for treatment of vascular disease and as a biological model for studying
      vascular development and pathophysiology.

PMID- 15486038
TI  - Disruption of growth hormone secretion alters Ca2+ current density and expression
      of Ca2+ channel and insulin-like growth factor genes in rat atria.
AB  - The influence of the growth hormone (GH)-insulin-like growth factor I (IGF-I)
      axis on expression of low-voltage-activated (LVA) Ca2+ current in atrial tissue
      was investigated using spontaneous dwarf (SpDwf) rats, a mutant strain that lacks
      GH. Atrial myocytes from SpDwf rats express LVA and high-voltage-activated (HVA)
      Ca2+ currents and the Ca2+ channel alpha1-subunit genes CaV1.2, CaV2.3, CaV3.1,
      and CaV3.2. LVA current density decreases significantly beginning at, or shortly
      after, birth in normal animals; however, its density is maintained in SpDwf rats
      at 1 pA/pF for > or =12 wk after birth. The abundance of mRNAs encoding CaV2.3
      and CaV3.2 declines with advancing age in normal atrial development, yet
      expression of CaV2.3 mRNA remains significantly elevated in older SpDwf animals.
      Quantitation of local transcript levels for mRNAs encoding IGF-I and IGF-I
      receptor (IGF-IR) also reveals significant differences in expression of these
      transcripts in atrial tissue of SpDwf animals compared with controls. In SpDwf
      rats, the abundance of IGF-IR mRNA remains elevated at many postnatal ages,
      whereas mRNA encoding IGF-I is maintained only in older animals. Physiological
      concentrations of IGF-I cause two- to threefold increases in LVA current density
      in primary cultures of atrial myocytes, and this effect is blocked by an
      antisense oligonucleotide targeting the IGF-IR. Thus disruption of GH production
      in SpDwf animals alters expression of atrial LVA Ca2+ channel and IGF genes as
      well as postnatal regulation of LVA Ca2+ current density, most likely acting
      through compensatory mechanisms via the local IGF-IR.

PMID- 15486039
TI  - Cyclooxygenase inhibition and baroreflex sensitivity in humans.
AB  - Animal studies suggest that prostanoids (i.e., such as prostacyclin) may
      sensitize or impair baroreceptor and/or baroreflex responsiveness depending on
      the site of administration and/or inhibition. We tested the hypothesis that acute
      inhibition of cyclooxygenase (COX), the rate-limiting enzyme in prostanoid
      synthesis, impairs baroreflex regulation of cardiac period (R-R interval) and
      muscle sympathetic nerve activity (MSNA) in humans and augments pressor
      reactivity. Baroreflex sensitivity (BRS) was determined at baseline (preinfusion)
      and 60 min after (postinfusion) intravenous infusion of a COX antagonist
      (ketorolac; 45 mg) (24 +/- 1 yr; n = 12) or saline (25 +/- 1 yr; n = 12). BRS was
      assessed by using the modified Oxford technique (bolus intravenous infusion of
      nitroprusside followed by phenylephrine). BRS was quantified as the slope of the
      linear portion of the 1) R-R interval-systolic blood pressure relation
      (cardiovagal BRS) and 2) MSNA-diastolic blood pressure relation (sympathetic BRS)
      during pharmacological changes in arterial blood pressure. Ketorolac did not
      alter cardiovagal (19.4 +/- 2.1 vs. 18.4 +/- 2.4 ms/mmHg preinfusion and
      postinfusion, respectively) or sympathetic BRS (-2.9 +/- 0.7 vs. -2.6 +/- 0.4
      arbitrary units.beat(-1).mmHg(-1)) but significantly decreased a plasma biomarker
      of prostanoid generation (plasma thromboxane B2) by 53 +/- 11%. Cardiovagal BRS
      (21.3 +/- 3.8 vs. 21.2 +/- 3.0 ms/mmHg), sympathetic BRS (-3.4 +/- 0.3 vs. -3.2
      +/- 0.2 arbitrary units.beat(-1).mmHg(-1)), and thromboxane B2 (change in -1 +/-
      12%) were unchanged in the control (saline infusion) group. Pressor responses to
      steady-state incremental (0.5, 1.0, and 1.5 microg.kg(-1).min(-1)) infusion (5
      min/dose) of phenylephrine were not altered by ketorolac (n = 8). Collectively,
      these data indicate that acute pharmacological antagonism of the COX enzyme does
      not impair BRS (cardiovagal or sympathetic) or augment pressor reactivity in
      healthy young adults.

PMID- 15486040
TI  - Plasma volume restoration with salt tablets and water after bed rest prevents
      orthostatic hypotension and changes in supine hemodynamic and endocrine
      variables.
AB  - Head-down bed rest changes the values of many cardiovascular and endocrine
      variables and also elicits significant hypovolemia. Because previous studies had
      not controlled for hypovolemia, it is unknown whether the reported changes were
      primary effects of bed rest or secondary effects of bed rest-induced hypovolemia.
      We hypothesized that restoring plasma volume with salt tablets and water after 12
      days of head-down bed rest would result in an absence of hemodynamic and
      endocrine changes and a reduced incidence of orthostatic hypotension. In 10 men,
      we measured changes from pre-bed-rest to post-bed-rest in venous and arterial
      pressures; heart rate; stroke volume; cardiac output; vascular resistance; plasma
      norepinephrine, epinephrine, vasopressin, renin activity (PRA), and aldosterone
      responses to different tilt levels (0 degrees, -10 degrees, 20 degrees, 30
      degrees, and 70 degrees); and plasma volume and platelet alpha2- and lymphocyte
      beta2-adrenoreceptor densities and affinities (0 degrees tilt only). Fluid
      loading at the end of bed rest restored plasma volume and resulted in the absence
      of post-bed-rest orthostatic hypotension and changes in supine hemodynamic and
      endocrine variables. Fluid loading did not prevent post-bed-rest increases in
      beta2-adrenoreceptor density or decreases in the aldosterone-to-PRA ratio (P =
      0.05 for each). Heart rate, epinephrine, and PRA responses to upright tilt after
      bed rest were increased (P < 0.05), despite the fluid load. These results suggest
      that incidents of orthostatic hypotension and many of the changes in supine
      hemodynamic and endocrine variables in volume-depleted bed-rested subjects occur
      secondarily to the hypovolemia. Despite normovolemia after bed rest, beta2
      adrenoreceptors were upregulated, and heart rate, epinephrine, and PRA responses
      to tilt were augmented, indicating that these changes are independent of volume
      depletion.

PMID- 15486041
TI  - Levosimendan improves LV systolic and diastolic performance at rest and during
      exercise after heart failure.
AB  - The new myofilament Ca2+ sensitizer levosimendan (LSM) is a positive inotropic
      and vasodilatory agent. Its beneficial effects have been demonstrated at rest in
      congestive heart failure (CHF). However, its effect during exercise (Ex) in CHF
      is unknown. We assessed the effects of LSM on left ventricular (LV) dynamics at
      rest and during Ex in eight conscious, instrumented dogs with pacing-induced CHF.
      After CHF, with dogs at rest, LSM decreased arterial elastance (Ea) and increased
      LV contractile performance as assessed by the slope of LV pressure-volume (P-V)
      relation. LSM caused a >60% increase in the peak rate of mitral flow (dV/dtmax)
      due to decreases in minimal LV pressure and the time constant of LV relaxation
      (tau). LV arterial coupling, quantified as the ratio of end-systolic elastance
      (Ees) to Ea, was increased from 0.47 to 0.85%. LV mechanical efficiency,
      determined as the ratio of stroke work to total P-V area, was improved from 0.54
      +/- 0.09 to 0.61 +/- 0.07. These beneficial effects persisted during Ex after
      CHF. Compared with CHF Ex dogs, treatment with LSM prevented Ex-induced abnormal
      increases in mean left atrial pressure and end-diastolic pressure and decreased
      Ees/Ea. With LSM treatment during CHF Ex, the early diastolic portion of the LV P
      V loop was shifted downward with decreased minimal LV pressure and tau values and
      a further augmented dV/dtmax. Ees/Ea improved, and mechanical efficiency further
      increased from 0.61 +/- 0.07 to 0.67 +/- 0.07, which was close to the value
      reached during normal Ex. After CHF, LSM produced arterial vasodilatation;
      improved LV relaxation and diastolic filling; increased contractility, LV
      arterial coupling, and mechanical efficiency; and normalized the response to Ex.

PMID- 15486042
TI  - OCRE: a novel domain made of imperfect, aromatic-rich octamer repeats.
AB  - SUMMARY: In this study, we describe a novel domain, OCRE, which is shared by the
      recently identified angiogenic factor VG5Q and a specific family of RNA-binding
      motif proteins. The OCRE domain is characterized by a 5-fold, imperfectly
      repeated octameric sequence, which includes a triplet of often-conserved aromatic
      amino acids predicted to form a beta-strand and in which the slightly modified
      fifth repeat might act as a repeat terminator. Although the function of this
      domain remains to be elucidated, the domain architecture of OCRE containing
      proteins and experimental data suggest a role in RNA metabolism and/or in
      signalling pathways activated by the tumor necrosis factor superfamily of
      cytokines.

PMID- 15486043
TI  - Reconstructing biological networks using conditional correlation analysis.
AB  - MOTIVATION: One of the present challenges in biological research is the
      organization of the data originating from high-throughput technologies. One way
      in which this information can be organized is in the form of networks of
      influences, physical or statistical, between cellular components. We propose an
      experimental method for probing biological networks, analyzing the resulting data
      and reconstructing the network architecture. METHODS: We use networks of known
      topology consisting of nodes (genes), directed edges (gene-gene interactions) and
      a dynamics for the genes' mRNA concentrations in terms of the gene-gene
      interactions. We proposed a network reconstruction algorithm based on the
      conditional correlation of the mRNA equilibrium concentration between two genes
      given that one of them was knocked down. Using simulated gene expression data on
      networks of known connectivity, we investigated how the reconstruction error is
      affected by noise, network topology, size, sparseness and dynamic parameters.
      RESULTS: Errors arise from correlation between nodes connected through
      intermediate nodes (false positives) and when the correlation between two
      directly connected nodes is obscured by noise, non-linearity or multiple inputs
      to the target node (false negatives). Two critical components of the method are
      as follows: (1) the choice of an optimal correlation threshold for predicting
      connections and (2) the reduction of errors arising from indirect connections
      (for which a novel algorithm is proposed). With these improvements, we can
      reconstruct networks with the topology of the transcriptional regulatory network
      in Escherichia coli with a reasonably low error rate.

PMID- 15486044
TI  - Activation of nicotinamide N-methyltransferase gene promoter by hepatocyte
      nuclear factor-1beta in human papillary thyroid cancer cells.
AB  - We previously demonstrated that the human nicotinamide N-methytransferase (NNMT)
      gene was highly expressed in many papillary thyroid cancers and cell lines. The
      expression in other papillary and follicular cancers or cell lines and normal
      thyroid cells was low or undetectable. To gain an understanding of the molecular
      mechanism of this cell-specific expression, the NNMT promoter was cloned and
      studied by luciferase reporter gene assay. The promoter construct was expressed
      highly in papillary cancer cell lines, including those with higher (e.g. BHP 2-7)
      and lower (e.g. BHP 14-9) NNMT gene expression, and expressed weakly in
      follicular thyroid cancer cell lines. Further study with 5'-deletion promoter
      construct suggested that the NNMT promoter was regulated differently in BHP 2-7
      and BHP 14-9 cells. In BHP 2-7 cells, promoter activity was dependent on an
      upstream sequence. In BHP 14-9 cells, sequence in the basal promoter region
      contributed notably to the overall promoter activity. RT-PCR or Western blot
      analysis indicated that hepatocyte nuclear factor-1beta (HNF-1beta) was expressed
      in only papillary cancer cell lines with high NNMT gene expression. HNF-1beta was
      not expressed or expressed very weakly in other papillary, follicular, and
      Hurthle cancer cell lines and primary cultures of normal thyroid cells and benign
      thyroid conditions. A HNF-1 binding site was identified in the NNMT basal
      promoter region. Mutations in this site decreased NNMT promoter activity in the
      HNF-1beta-positive BHP 2-7 cells, but not in the HNF-1beta-negative BHP 14-9
      cells. HNF-1beta bound to the HNF-1 site specifically as a homodimer as
      determined by gel retardation assays with HNF-1beta-specific antibody.
      Cotransfection of a HNF-1beta expression plasmid increased NNMT promoter activity
      significantly in both HNF-1beta-positive and -negative thyroid cancer cell lines
      and Hep G2 liver cancer cells. Furthermore, transient expression of HNF-1beta in
      BHP 14-9 cells increased endogenous NNMT protein levels. In summary, HNF-1beta
      functions as a transcription activator for NNMT gene expression in some papillary
      thyroid cancer cells.

PMID- 15486045
TI  - Progesterone receptors induce cell cycle progression via activation of mitogen
      activated protein kinases.
AB  - Progestins induce proliferation of breast cancer cells and are implicated in the
      development of breast cancer. The effects of progestins are mediated by
      progesterone receptors (PRs), although it is unclear whether proliferative
      effects are delivered through activities as ligand-activated transcription
      factors or via activation of cytoplasmic kinases. We report that progestin
      induces S phase entry of T47D cells stably expressing either wild-type (wt) PR-B
      or a transcriptionally impaired PR-B harboring a point mutation at Ser294, a
      ligand-dependent and MAPK consensus phosphorylation site (S294A). Both wt and
      S294A PR are capable of activating p42/p44 MAPKs and promoting proliferation.
      However, cells expressing wt, but not S294A PR, exhibited enhanced proliferation
      in response to combined epidermal growth factor and progestin. S phase
      progression correlated with up-regulation of cyclin D1. The PR antagonist RU486
      also induced MAPK activation, increased cyclin D1 expression, and stimulated S
      phase entry, which was blocked by inhibition of either p42/p44 or p38 MAPKs,
      whereas proliferation induced by R5020 was sensitive only to p42/p44 MAPK
      inhibition. MCF-7 cells stably expressing a mutant PR unable to bind c-Src and
      activate MAPK failed to support progestin-induced proliferation. These data
      suggest that PR mediate cell cycle progression primarily through activation of
      cytoplasmic kinases and independently of direct regulation of transcription,
      whereas the coordinate regulation of both aspects of PR action are required for
      enhanced proliferation in response to progestins in the presence of growth
      factors. Targeting the ability of steroid receptors to activate MAPKs may be
      beneficial for breast cancer patients.

PMID- 15486046
TI  - Mechanism of SHIP-mediated inhibition of insulin- and platelet-derived growth
      factor-stimulated mitogen-activated protein kinase activity in 3T3-L1 adipocytes.
AB  - The Src homology 2-containing 5' inositolphosphatases (SHIP and SHIP2)
      dephosphorylate 3'-phosphorylated PtdIns on the 5' position, decreasing
      intracellular levels of PtdIns 3,4,5-P3. In the current study, we investigated
      the role of SHIP in insulin and platelet-derived growth factor (PDGF) signaling
      by expressing wild-type (WT) and catalytically inactive SHIPDeltaIP in 3T3-L1
      adipocytes, utilizing adenoviral infection. Insulin and PDGF both stimulated
      tyrosine phosphorylation of SHIP-WT and of SHIPDeltaIP, and tyrosine
      phosphorylation of SHIP-associated proteins increased after ligand stimulation.
      Tyrosine-phosphorylated PDGFR, IR, and insulin receptor substrate-1 all
      immunoprecipitated with SHIP. Expression of WT and DeltaIP mutant SHIP did not
      affect tyrosine phosphorylation of either the insulin or the PDGF receptor, or
      the expression of insulin receptor substrate-1 and Shc proteins. Both SHIP-WT and
      SHIPDeltaIP blocked insulin and PDGF-induced MAPK and MAPK kinase phosphorylation
      as well as, GTP-bound Ras activity, suggesting that the catalytic activity of
      SHIP is not necessary for these effects. SHIP associated with Shc upon ligand
      stimulation, indicating that the SHIP-Shc association is phosphorylation
      dependent. This association was primarily between the SHIP-SH2 domain and the
      phosphorylated tyrosine residues of Shc because no association was observed when
      the 3YF-Shc mutant was coexpressed with SHIP. The Shc*Grb2 association was not
      compromised by SHIP expression, despite complete inhibition of the Ras/MAPK
      pathway. Interestingly, son-of-sevenless (SOS) protein normally found in Grb2
      complexes was markedly reduced in SHIP expressing cells, whereas the displaced
      SOS was recovered when the post-Grb2-IP supernatants were blotted with anti-SOS
      antibody. Thus, SHIP competes son-of-sevenless (SOS) away from Shc-Grb2. In
      summary, 1) SHIP-WT and SHIPDeltaIP expression inhibit insulin and PDGF
      stimulated Ras, MAPK kinase, and MAPK activities; 2) SHIP associates with
      tyrosine phosphorylated Shc, and the proline-rich sequences in SHIP associate
      with Grb2 and titrate out SOS to form Shc*Grb2*SHIP complexes; and 3)
      dissociation of SOS from the Shc*Grb2 complex inhibits Ras GTP loading, leading
      to decreased signaling through the MAPK pathway.

PMID- 15486047
TI  - Dissecting the basis of nongenomic activation of endothelial nitric oxide
      synthase by estradiol: role of ERalpha domains with known nuclear functions.
AB  - Estradiol stimulates endothelial nitric oxide synthase (eNOS) via the activation
      of plasma membrane (PM)-associated estrogen receptor (ER) alpha. The process
      requires Src and erk signaling and eNOS phosphorylation by phosphoinositide 3
      kinase (PI3 kinase)-Akt kinase, with Src and PI3 kinase associating with ERalpha
      upon ligand activation. To delineate the basis of nongenomic eNOS stimulation,
      the potential roles of ERalpha domains necessary for classical nuclear function
      were investigated in COS-7 cells. In cross-linking studies, estradiol-17beta (E2)
      caused PM-associated ERalpha to form dimers. However, eNOS activation by E2 was
      unaltered for a dimerization-deficient mutant ERalpha (ERalphaL511R). In
      contrast, ERalpha mutants lacking the nuclear localization signals (NLS), NLS2,3
      (ERalphaDelta250-274) or the DNA binding domain (ERalphaDelta185-251), which
      targeted normally to PM and caveolae/rafts, were incapable of activating eNOS.
      The loss of NLS2/NLS3 prevented Src and erk activation, and it altered ligand
      induced PI3 kinase-ERalpha interaction and prevented eNOS phosphorylation. Loss
      of the DNA binding domain did not change E2 activation of Src or erk, but ligand
      induced PI3 kinase-ERalpha binding and eNOS phosphorylation did not occur. Thus,
      dimerization is not required for ERalpha coupling to eNOS; however, NLS2/NLS3
      plays a role in Src activation, and the DNA binding region is involved in the
      dynamic interaction between ERalpha and PI3 kinase.

PMID- 15486048
TI  - Coimmunoprecipitation of UDP-glucuronosyltransferase isoforms and cytochrome P450
      3A4.
AB  - Coimmunoprecipitation was used to investigate protein-protein interactions
      between several UDP-glucuronosyltransferase (UGT) isoforms and cytochrome P450
      3A4. Solubilized human liver microsomes were incubated with specific antibodies
      to UGT2B7, UGT1A6, UGT1A1, and CYP3A4, and the immunoprecipitates were run on SDS
      polyacrylamide gel electrophoresis. Western blots showed that UGT2B7, UGT1A6,
      UGT1A1, and CYP3A4 were successfully immunoprecipitated with the specific
      antibodies for each enzyme. Upon immunoprecipitating UGT2B7, the corresponding
      immunoblot showed that UGT1A6, UGT1A1, and CYP3A4 were immunoprecipitated.
      Similar studies found that different UGT isoforms or CYP3A4 immunoprecipitated
      along with the original immunoprecipitating enzyme. These data suggest that UGT
      isoforms may form complexes (dimers, tetramers, etc.) with each other in the
      endoplasmic reticulum and nuclear envelope. In addition, the UGT isoforms tested
      here may have interacted with CYP3A4 in the endoplasmic reticulum, suggesting
      that these enzymes may cooperate in the excretion of compounds in a multistep
      metabolic process.

PMID- 15486049
TI  - Proteasomal degradation of human CYP1B1: effect of the Asn453Ser polymorphism on
      the post-translational regulation of CYP1B1 expression.
AB  - Allelic variations in CYP1B1 are reported to modulate the incidence of several
      types of cancer. To provide a mechanistic basis for this association, we
      investigated the impact of nonsilent allelic changes on the intracellular levels
      and post-translational regulation of CYP1B1 protein. When transiently expressed
      in COS-1 cells, either in the presence or absence of recombinant cytochrome P450
      reductase, the cellular level of the CYP1B1.4 allelic variant (containing a Ser
      at the amino acid position 453; Ser453) was 2-fold lower compared with the other
      four allelic CYP1B1 proteins (containing Asn453), as analyzed by both
      immunoblotting and ethoxyresorufin O-deethylase activity. This difference was
      caused by post-translational regulation; as in the presence of cycloheximide, the
      rate of degradation of immunodetectable and enzymatically active CYP1B1.4 was
      distinctly faster than that of CYP1B1.1. Pulse-chase analysis revealed that the
      half-life of CYP1B1.4 was a mere 1.6 h compared with 4.8 h for CYP1B1.1. The
      presence of the proteasome inhibitor MG132 [N-benzoyloxycarbonyl (Z)-Leu
      Leuleucinal] increased the stability not only of immunodetectable CYP1B1, but
      also--unexpectedly given the size of the proteasome access channel--increased the
      stability of enzymatically active CYP1B1. The data presented herein also
      demonstrate that CYP1B1 is targeted for its polymorphism-dependent degradation by
      polyubiquitination but not phosphorylation. Our results importantly provide a
      mechanism to explain the recently reported lower incidence of endometrial cancer
      in individuals carrying the CYP1B1*4 compared with the CYP1B1*1 haplo-type. In
      addition, the mechanistic paradigms revealed herein may explain the strong
      overexpression of CYP1B1 in tumors compared with nondiseased tissues.

PMID- 15486050
TI  - Role of human nucleoside transporters in the cellular uptake of two inhibitors of
      IMP dehydrogenase, tiazofurin and benzamide riboside.
AB  - Benzamide riboside (BR) and tiazofurin (TR) are converted to analogs of NAD that
      inhibit IMP dehydrogenase (IMPDH), resulting in cellular depletion of GTP and
      dGTP and inhibition of proliferation. The current work was undertaken to identify
      the human nucleoside transporters involved in cellular uptake of BR and TR and to
      evaluate their role in cytotoxicity. Transportability was examined in Xenopus
      laevis oocytes and Saccharomyces cerevisiae that produced individual recombinant
      human concentrative nucleoside transporter (CNT) and equilibrative nucleoside
      transporter (ENT) types (hENT1, hENT2, hCNT1, hCNT2, or hCNT3). TR was a better
      permeant than BR with a rank order of transportability in oocytes of hCNT3 >>
      hENT1 > hENT2 > hCNT2 >> hCNT1. The concentration dependence of inhibition of
      [(3)H]uridine transport in S. cerevisiae by TR exhibited lower K(i) values than
      BR: hCNT3 (5.4 versus 226 microM), hENT2 (16 versus 271 microM), hENT1 (57 versus
      168 microM), and hCNT1 (221 versus 220 microM). In cytotoxicity experiments, BR
      was more cytotoxic than TR to cells that were either nucleoside transport
      defective or -competent, and transport-competent cells were more sensitive to
      both drugs. Exposure to nitrobenzylmercaptopurine ribonucleoside conferred
      resistance to BR and TR cytotoxicity to hENT1-containing CEM cells, thereby
      demonstrating the importance of transport capacity for manifestation of
      cytoxicity. A breast cancer cell line with mutant p53 exhibited 9-fold higher
      sensitivity to BR than the otherwise similar cell line with wild-type p53,
      suggesting that cells with mutant p53 may be potential targets for IMPDH
      inhibitors. Further studies are warranted to determine whether this finding can
      be generalized to other cell types.

PMID- 15486051
TI  - Responses to a saline load in gonadotropin-releasing hormone antagonist
      pretreated premenopausal women receiving progesterone or estradiol-progesterone
      therapy.
AB  - The effects of estradiol (E(2)) and progesterone (P(4)) on fluid and sodium
      regulation may have important clinical implications with respect to
      cardiovascular and renal disease as well as reproductive syndromes such as
      preeclampsia and ovarian hyperstimulation syndrome. We tested the hypothesis that
      sodium excretion is reduced in response to a sodium load during combined P(4)
      E(2) treatment, but P(4) administration alone has little effect on sodium
      regulation. Fifteen women (22 +/- 2 yr) used a GnRH antagonist to suppress
      endogenous E(2) and P(4) for 9 d; for d 4-9, eight subjects used P(4) (200 mg/d),
      and seven subjects used P(4) with E(2) (two E(2) patches, 0.1 mg/d each). On d 3
      and 9, isotonic saline (0.9% NaCl) was infused [120 min at 0.1 ml/kg body weight
      (BW).min], followed by 120 min of rest. Compared with GnRH antagonist alone,
      P([P4]) increased from 1.6 +/- 0.8 to 9.4 +/- 2.3 ng/ml (5.1 +/- 2.5 to 29.9 +/-
      7.3 nmol/liter, P < 0.05) in the P(4) treated group, with no change in P([E2]).
      In the P(4)-E(2) treated group P([P4]) increased from 1.6 +/- 0.5 to 6.7 +/- 0.6
      ng/ml (5.1 +/- 1.6 to 21.3 +/- 1.6 nmol/liter, P < 0.05 and P([E2]) increased
      from 17.9 +/- 6.3 to 200 +/- 41 pg/ml (65.7 +/- 23 to 734.6 +/- 150.0 pmol/liter,
      P < 0.05). Before isotonic saline infusion, renal sodium and water excretion were
      similar under all conditions, but during isotonic saline infusion, cumulative
      sodium excretion was lower in the P(4)-E(2) treated women (34.1 +/- 5.1 mEq)
      compared with GnRH antagonist (50.2 +/- 11.4 mEq). Sodium excretion was
      unaffected by P(4) treatment (48.0 +/- 8.2 and 41.2 +/- 5.1 mEq, for GnRH
      antagonist and P(4)). Compared with GnRH antagonist alone, P(4)-E(2) treatment
      increased distal sodium reabsorption and transiently decreased proximal sodium
      reabsorption, whereas P(4) treatment did not alter either distal or proximal
      sodium reabsorption. Before isotonic saline infusion, the plasma aldosterone
      (Ald) concentration was greater during P(4) treatment (153 +/- 25 pg/ml; 3883 +/-
      1102 pmol/liter) and P(4)-E(2) treatment (242 +/- 47 pg/ml; 6373 +/- 1390
      pmol/liter) than during their respective GnRH antagonist alone treatments [96 +/-
      13 and 148 +/- 47 pg/ml (2598 +/- 475 and 3284 +/- 973 pmol/liter) for P(4) and
      combined P(4)-E(2), respectively]. Compared with GnRH antagonist alone
      treatments, preisotonic saline infusion plasma renin activity was greater only
      with P(4)-E(2) treatment, whereas the plasma atrial natriuretic peptide
      concentration was lower only with P(4) treatment. Isotonic saline infusion
      suppressed plasma Ald under all conditions, but decreased plasma renin activity
      only with P(4)-E(2) treatment (average decrease, 1.3 +/- 0.5 ng/ml angiotensin
      I.h; P < 0.05). In summary, we found that P(4)-E(2) treatment decreased sodium
      excretion via either renin-angiotensin-Ald system stimulation or direct effects
      on kidney tubules. P(4) treatment at these plasma concentrations had no
      independent effect on the renal response to acute sodium loading. These data
      suggest that E(2) is the more powerful reproductive hormone involved in sodium
      retention relative to P(4), and that estrogen-induced up-regulation of P(4)
      receptors is required for the effects of P(4) on sodium regulation.

PMID- 15486052
TI  - An inflammation score is better associated with basal than stimulated surrogate
      indexes of insulin resistance.
AB  - Most studies describe the association between one particular inflammatory marker
      and insulin resistance (IR), features of the metabolic syndrome, or progression
      to type 2 diabetes. We aimed to build an Inflammation Score as a tool to measure
      IR-associated inflammatory activity and to evaluate the ability of different
      surrogate indexes of IR to reflect the inflammatory state. We studied 81
      subjects, aged 47.7 +/- 12 yr with a body mass index of 28.3 +/- 4 kg/m(2). The
      Inflammation Score was composed of: white blood cell count, erythrocyte
      sedimentation rate, C-reactive protein, and soluble fraction of TNF-alpha
      receptors 1 and 2. All the subjects underwent a frequently sampled iv glucose
      tolerance test, an oral glucose tolerance test, and surrogate indexes of IR were
      calculated. Each increase in the Inflammation Score was associated with a
      progressive increase in IR. We found significant differences across categories (0
      1, 2, 3, and 4-5 points in the score) in age (P = 0.048), waist circumference (P
      = 0.015), body mass index (P = 0.013), blood pressure (P = 0.005), and uric acid
      (P = 0.031). The Inflammation Score was significantly associated with all but
      three of the surrogate IR indexes [2-h insulin glucose ratio, Gutt's insulin
      sensitivity (SI) index, and Avignon's 2-h SI index]. Surrogate indexes obtained
      from basal values showed a similar correlation with the Inflammation Score than
      the SI from frequently sampled iv glucose tolerance test. In summary, the
      Inflammation Score is a useful tool in the evaluation of IR-associated
      inflammatory activity. The surrogate indexes obtained using fasting glucose and
      insulin appear to better reflect this inflammatory state. Basal rather than
      stimulated indexes should be used in the evaluation of therapeutic measures aimed
      at modifying IR-associated inflammatory activity.

PMID- 15486053
TI  - Prevalence of mutations and functional analyses of melanocortin 4 receptor
      variants identified among 750 men with juvenile-onset obesity.
AB  - Mutations in the gene encoding the melanocortin 4 receptor (MC4R) are associated
      with the most common monogenic form of obesity. We examined 750 Danish men with
      juvenile-onset obesity (body mass index 33.3 +/- 2.4 kg/m(2)) and 706 control
      subjects (body mass index 21.4 +/- 2.1 kg/m(2)) for mutations in MC4R. A total of
      14 different mutations were identified of which two, Ala219Val and Leu325Phe,
      were novel variants. The variant receptor, Leu325Phe, was unable to bind [Nle4,d
      Phe7]-alphaMSH, whereas the Ala219Val variant showed a significantly impaired
      melanotan II induction of cAMP, compared with the wild-type receptor. The
      remaining 11 mutations have previously been reported, but selected MC4R variants
      were further characterized in vitro in the present study. A previously identified
      nonsense mutation, Tyr35stop, had a relatively high allele frequency (0.6%),
      suggesting a possible founder effect in the Danish population. This study shows a
      carrier frequency of 2.5% of pathogenic mutations in the MC4R gene in a
      population-based study of obese men. Thus, variation in this gene is the most
      common known specific genetic cause of obesity among Scandinavian men.

PMID- 15486054
TI  - Early appearance of the metabolic syndrome in socially reared bonnet macaques.
AB  - Among 250 laboratory-born bonnet macaques living in social groups and maintained
      on commercial monkey chow, we measured weight, crown-rump length, sagittal
      abdominal diameter (SAD), and fasting serum insulin, glucose, triglycerides, high
      density lipoproteins, low-density lipoproteins, and total cholesterol. Body mass
      index (BMI = weight/crown-rump length(2)), and insulin resistance determined by
      the insulin/glucose ratio (IGR) and homeostasis model assessment, were measured.
      We defined the metabolic syndrome using a composite score based on morphometry,
      insulin resistance, and serum lipid levels, analogous to clinical criteria.
      Elevated BMI was associated with significantly greater SAD, insulin, IGR,
      homeostasis model assessment, and triglycerides. Among 120 adult monkeys aged 5
      17 yr, males (n = 48) had higher BMI, SAD, insulin, and IGR levels than females,
      independent of age. Sixteen of 113 adult monkeys and five of 36 peripubertal
      subjects, aged 3-4 yr (14%), met our criteria for the metabolic syndrome, as did
      four of 12 monkeys, aged 20-28 yr. Markers of the metabolic syndrome are present
      by 3-4 yr of age in our colony and are observed across the life span in the
      absence of conventional obesifying interventions. Socially reared and housed
      bonnet macaques may provide a useful model for studying the pathogenesis,
      prevention, and treatment of the metabolic syndrome.

PMID- 15486055
TI  - Functional analysis of a novel androgen receptor mutation, Q902K, in an
      individual with partial androgen insensitivity.
AB  - Androgen insensitivity syndrome (AIS) is caused by defects in the androgen
      receptor (AR) that render the AR partially or completely inactive. As a result,
      embryonic sex differentiation is impaired. Here, we describe a novel mutation in
      the AR found in a patient with partial AIS. The mutation results in a
      substitution of a glutamine (Q) by a lysine (K) residue at position 902, Q902K.
      The AR Q902K mutation was investigated in vitro with respect to its functional
      properties. The equilibrium dissociation constants (K(d)s) of AR Q902K in the
      presence of either the synthetic androgen R1881 or the natural ligand DHT were
      slightly elevated. The R1881 dissociation rate (t(1/2)) was increased 3-fold for
      AR Q902K compared with wild type. Transcriptional activity was decreased to 85%
      of wild type, and the dose-response curve revealed that the sensitivity to
      hormone was decreased due to the mutation. Furthermore, the 114-kDa androgen
      induced phosphorylated AR protein band was not detectable in genital skin
      fibroblasts. However, it could be detected in transfected CHO cells expressing
      the mutant receptor in the presence of 10 and 100 nm R1881. Functional
      interaction assays and a GST pull-down assay showed that the interaction between
      the NH2 and COOH terminus of AR Q902K was reduced to 50% of wild type.
      Furthermore, the transactivation by the coactivator TIF2 (transcriptional
      intermediary factor 2) was decreased 2- to 3-fold. The half-maximal response in
      both assays was shifted to a higher hormone concentration compared with wild
      type. These results indicate that residue Q902 is involved in TIF2 and NH2/COOH
      interaction and that the Q to K mutation results in a mild impairment of AR
      function, which can explain the partial AIS phenotype of the patient.

PMID- 15486056
TI  - Neuroactive pregnanolone isomers during pregnancy.
AB  - The pregnanolone isomers (PI) allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20
      one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one), isopregnanolone (3beta
      hydroxy-5alpha-pregnan-20-one), epipregnanolone (3beta-hydroxy-5beta-pregnan-20
      one), progesterone, and estradiol were measured in 138 pregnant women. The
      sampling was carried out from the first through the 10th month of pregnancy. Gas
      chromatography-mass spectrometry analysis and RIA were used for the measurement
      of steroid levels. The ratios of individual PI were similar to those found
      previously around parturition: about 25:10:7:1 for allopregnanolone,
      pregnanolone, isopregnanolone, and epipregnanolone, respectively. All the PI
      showed a significant increase during pregnancy, which was more pronounced in the
      3alpha-steroids. The results indicated changing ratios between 3alpha- and 3beta
      PI and between 5alpha- and 5beta-PI throughout pregnancy. The constant
      allopregnanolone/isopregnanolone ratio found through pregnancy weakened the
      hypothesis of the role of isopregnanolone in the onset of parturition. The ratio
      of estradiol (stimulating uterine activity) to 5alpha-PI and epipregnanolone
      exhibited significant changes during pregnancy in favor of estradiol up to the
      sixth or seventh month, in contrast to the constant estradiol/pregnanolone ratio.
      A pregnancy-stabilizing role of pregnanolone, counterbalancing the stimulating
      effect of estradiol on the onset of parturition, was suggested.

PMID- 15486057
TI  - Generation of purified oligodendrocyte progenitors from embryonic stem cells.
AB  - Demyelination is a key component in the pathogenesis of many neurological
      disorders. Transplantation of myelinating cells may offer a therapeutic approach
      to restore neurological function in these diseases. Recent findings suggest that
      pluripotent embryonic stem (ES) cells can serve as an unlimited donor source for
      neural transplantation. The clinical application of ES cells for myelin repair
      will depend critically on the ability to enrich oligodendroglial progenitors in
      high purity. Combining controlled differentiation in the presence of growth
      factors and genetic lineage selection, we devised a cell culture protocol
      yielding highly purified oligodendrocyte progenitors. Murine ES cell clones
      stably transfected with a construct encoding the beta-galactosidase-neomycine
      phosphotransferase fusion protein (beta(geo)) under control of the 2'3'-cyclic
      nucleotide 3'-phosphodiesterase (CNP) promoter were differentiated into
      bipotential glial precursors. Subsequent induction of a CNP-positive stage and
      selection in neomycine resulted in a homogenous cell population with a pre
      oligodendrocyte phenotype. The selected cells continued to proliferate in the
      presence of FGF-2 and PDGF and, upon growth factor withdrawal, differentiated
      into mature galactocerebroside (GalC)-positive oligodendrocytes. Transplantation
      studies in myelin-deficient (md) rats indicate that ES cell-derived
      oligodendrocyte progenitors generated with this method may serve as an attractive
      donor source for myelin repair.

PMID- 15486058
TI  - Soluble Robo4 receptor inhibits in vivo angiogenesis and endothelial cell
      migration.
AB  - Roundabout receptors are molecular guidance molecules that function by
      interaction with Slit proteins to regulate axon guidance, neuronal migration, and
      leukocyte chemotaxis. We recently isolated a novel roundabout gene, called Robo4,
      which is restricted in expression to the endothelium, notably in areas of
      angiogenesis. The aim of this study was to use the soluble extracellular domain
      of Robo4 as a probe of function in angiogenesis and endothelial biology. Thus,
      the soluble extracellular domain of the receptor (Robo4Fc) showed diverse in vivo
      and in vitro activities including 1) inhibition of angiogenesis in vivo in the
      rodent subcutaneous sponge model, 2) inhibition of tube formation in the rat
      aortic ring assay, 3) inhibition of VEGF- and bFGF-stimulated endothelial cell
      migration, and 4) inhibition of endothelial proliferation. To assess whether
      Robo4Fc was inhibiting Slit-mediated effects, we determined whether Robo4 and
      Slit interact. Recombinant Slits-1, -2, and -3 were shown by immunoprecipitation
      and BiaCore analysis to bind to Robo1 but not Robo4. Further study of the role of
      Robo4 in angiogenesis appears justified.

PMID- 15486059
TI  - Cytosolic phospholipase A2 mediates neuronal apoptosis induced by soluble
      oligomers of the amyloid-beta peptide.
AB  - Recent data have revealed that soluble oligomeric forms of amyloid peptide
      (Abeta) may be the proximate effectors of the neuronal injury and death occurring
      in Alzheimer's disease (AD). However, the molecular mechanisms associated with
      the neuronal cell death induced by the nonfibrillar Abeta remain to be
      elucidated. In this study, we investigated the role of the cytosolic Ca2+
      dependent phospholipase A2 (cPLA2), and its associated metabolic pathway, i.e.,
      the arachidonic acid (AA) cascade, in the apoptotic cell death induced by soluble
      oligomers of Abeta. The treatment of rat cortical neurons with low concentrations
      of soluble Abeta(1-40) or Abeta(1-42) peptide resulted in an early calcium
      dependent release of AA associated with a transient relocalization of cPLA2. Both
      cPLA2 antisense oligonucleotides and a selective inhibitor of cPLA2 activity
      abolished the release of AA from neurons and also protected cells against
      apoptosis induced by Abeta. Furthermore, inhibitors of the PKC, p38, and MEK/ERK
      pathways that are involved in cPLA2 phosphorylation and activation reduced Abeta
      induced cell death. Finally, we demonstrate that inhibitors of cyclooxygenase-2
      reduced the Abeta-induced cell death by 55%. Our studies suggest a novel neuronal
      response of soluble oligomers of Abeta, which occurs through a cPLA2 signaling
      cascade and an AA-dependent death pathway. This may prove to be crucial in AD
      processes and could provide important targets for drug development.

PMID- 15486060
TI  - Notch ligands Delta 1 and Jagged1 transmit distinct signals to T-cell precursors.
AB  - Signaling through the Notch pathway plays an essential role in inducing T-lineage
      commitment and promoting the maturation of immature thymocytes. Using an in vitro
      culture system, we show that 2 different classes of Notch ligands, Jagged1 or
      Delta1, transmit distinct signals to T-cell progenitors. OP9 stromal cells
      expressing either Jagged1 or Delta1 inhibit the differentiation of DN1 thymocytes
      into the B-cell lineage, but only the Delta1-expressing stromal cells promote the
      proliferation and maturation of T-cell progenitors through the early double
      negative (DN) stages of thymocyte development. Whereas the majority of bone
      marrow-derived stem cells do not respond to Jagged1 signals, T-cell progenitors
      respond to Jagged1 signals during a brief window of their development between the
      DN1 and DN3 stages of thymic development. During these stages, Jagged1 signals
      can influence the differentiation of immature thymocytes along the natural killer
      (NK) and gamma delta T-cell lineages.

PMID- 15486061
TI  - Phytosphingosine in combination with ionizing radiation enhances apoptotic cell
      death in radiation-resistant cancer cells through ROS-dependent and -independent
      AIF release.
AB  - The use of chemical modifiers as radiosensitizers in combination with low-dose
      irradiation may increase the therapeutic effect on cancer by overcoming a high
      apoptotic threshold. Here, we showed that phytosphingosine treatment in
      combination with gamma-radiation enhanced apoptotic cell death of radiation
      resistant human T-cell lymphoma in a caspase-independent manner. Combination
      treatment induced an increase in intracellular reactive oxygen species (ROS)
      level, mitochondrial relocalization of B-cell lymphoma-2(Bcl-2)-associated X
      protein (Bax), poly-adenosine diphosphate (ADP)-ribose polymerase 1 (PARP-1)
      activation, and nuclear translocation of apoptosis-inducing factor (AIF). siRNA
      targeting of AIF effectively protected cells from the combination treatment
      induced cell death. An antioxidant, N-acetyl-L-cysteine (NAC), inhibited Bax
      relocalization and AIF translocation but not PARP-1 activation. Moreover,
      transfection of Bax-siRNA significantly inhibited AIF translocation. Pretreatment
      of PARP-1 inhibitor, DPQ (3,4-dihydro-5-[4-(1-piperidinyl)-butoxy]-1(2H)
      isoquinolinone), or PARP-1-siRNA also partially attenuated AIF translocation,
      whereas the same treatment did not affect intracellular ROS level and Bax
      redistribution. Taken together, these results demonstrate that enhancement of
      cell death of radiation-resistant cancer cells by phytosphingosine treatment in
      combination with gamma-radiation is mediated by nuclear translocation of AIF,
      which is in turn mediated both by ROS-dependent Bax relocalization and ROS
      independent PARP-1 activation. The molecular signaling pathways that we
      elucidated in this study may provide potential drug targets for radiation
      sensitization of cancers refractive to radiation therapy.

PMID- 15486062
TI  - Anti-human CTLA-4 monoclonal antibody promotes T-cell expansion and immunity in a
      hu-PBL-SCID model: a new method for preclinical screening of costimulatory
      monoclonal antibodies.
AB  - When adopting basic principles learned in mice to clinical application in humans,
      it is often difficult to distinguish whether a "translation" fails because of an
      invalid target in the human disease or because the therapeutic agents are not
      optimal for the human target. It is, therefore, desirable to develop preclinical
      models to optimize therapies for human targets using in vivo settings. Although
      anti-mouse CTLA-4 antibodies are known to enhance immune responses in vivo, their
      effect on T-cell activation in vitro ranges from enhancement to inhibition. Here
      we use the hu-PBL-SCID mouse model of Epstein-Barr virus (EBV)-associated
      lymphoma development to screen a panel of anti-human CTLA-4 monoclonal antibodies
      (mAbs) for their effect on human lymphocytes in an in vivo "humanized"
      environment. We report significant heterogeneity of anti-human CTLA-4 mAbs in
      enhancing the expansion of human T cells in mice, and this heterogeneity cannot
      be attributed to immunoglobulin isotypes or affinity for CTLA-4. These data
      validate the development of additional screening tools, such as the one
      described, to further characterize functional activity of antihuman antibodies
      before proceeding with clinical translation to human studies.

PMID- 15486063
TI  - Induction of tolerance using Fas ligand: a double-edged immunomodulator.
AB  - Apoptosis mediated by Fas ligand (FasL) interaction with Fas receptor plays a
      pivotal regulatory role in immune homeostasis, immune privilege, and self
      tolerance. FasL, therefore, has been extensively exploited as an immunomodulatory
      agent to induce tolerance to both autoimmune and foreign antigens with
      conflicting results. Difficulties associated with the use of FasL as a
      tolerogenic factor may arise from (1) its complex posttranslational regulation,
      (2) the opposing functions of different forms of FasL, (3) different modes of
      expression, systemic versus localized and transient versus continuous, (4) the
      level and duration of expression, (5) the sensitivity of target tissues to
      Fas/FasL-mediated apoptosis and the efficiency of antigen presentation in these
      tissues, and (6) the types and levels of cytokines, chemokines, and
      metalloproteinases in the extracellular milieu of the target tissues. Thus, the
      effective use of FasL as an immunomodulator to achieve durable antigen-specific
      immune tolerance requires careful consideration of all of these parameters and
      the design of treatment regimens that maximize tolerogenic efficacy, while
      minimizing the non-tolerogenic and toxic functions of this molecule. This review
      summarizes the current status of FasL as a tolerogenic agent, problems associated
      with its use as an immunomodulator, and new strategies to improve its therapeutic
      potential.

PMID- 15486064
TI  - Activated protein C induces the release of microparticle-associated endothelial
      protein C receptor.
AB  - Activated protein C (APC) treatment is now used for patients with severe sepsis.
      We investigated its effect in vitro on primary, physiologically relevant cells
      and demonstrate a novel mechanism of endothelial protein C receptor (EPCR)
      release that is not inhibited by metalloproteinase inhibitors. Exposure of human
      umbilical vein endothelial cells or monocytes to APC (6.25-100 nM) results in the
      release of EPCR-containing microparticles, as demonstrated by confocal microscopy
      and characterized through flow cytometry, enzyme-linked immunosorbent assay
      quantitation of isolated microparticles, and Western blotting. The phenomenon is
      time- and concentration-dependent and requires the APC active site, EPCR, and
      protease activated receptor 1 (PAR1) on endothelial cells. Neither protein C nor
      boiled or D-Phe-Pro-Arg-chloromethylketone-blocked APC can induce microparticle
      formation and antibody blockade of EPCR or PAR1 cleavage and activation abrogates
      this APC action. Coincubation with hirudin does not alter the APC effect. The
      released microparticle bound is full-length EPCR (49 kDa) and APC retains factor
      V-inactivating activity. Although tumor necrosis factor-alpha (10 ng/mL) can also
      induce microparticle-associated EPCR release to a similar extent as APC (100 nM),
      it is only APC-induced microparticles that contain bound APC. This novel
      observation could provide new insights into the consequences of APC therapy in
      the septic patient.

PMID- 15486065
TI  - Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL
      23 expression in human dendritic cells: a novel role for the cAMP pathway.
AB  - The interleukin-12 (IL-12) cytokine family plays important roles in the
      orchestration of innate and adaptive immunity by dendritic cells (DCs). The
      regulation of IL-12 expression has been thoroughly studied, but little is known
      about factors governing the expression of IL-23 and IL-27, 2 novel IL-12 family
      members acting on memory and naive T cells, respectively. We report that the
      expression of these cytokines by DCs was critically dependent on the mode of
      activation. DC activation by CD40L predominantly induced IL-12. Ligands of the
      Toll-like receptor (TLR) 3 and TLR4 induced IL-12 and IL-27, whereas exposure to
      intact Escherichia coli resulted in high expression of IL-12, IL-27, and IL-23.
      The nucleotide adenosine triphosphate (ATP) has been shown to inhibit IL-12
      production by P2 receptors. We found that ATP also inhibited IL-27 expression but
      enhanced IL-23 expression. Interestingly, the reciprocal regulation of IL-12/IL
      27 and IL-23 by ATP was mediated by 2 distinct P2 receptors and was also induced
      by prostaglandin E(2) by cyclic adenosine monophosphate (cAMP)-elevating EP2/EP4
      receptors. As a consequence, DCs were selectively impaired in their ability to
      induce interferon-gamma (IFN-gamma) in naive T cells but continued to promote IFN
      gamma and IL-17 production in memory T cells. These studies identify P2 receptors
      as promising targets for the design of novel strategies to manipulate specific
      stages of T-cell responses and to treat IL-12- and IL-23-mediated disorders.

PMID- 15486066
TI  - The impact of the methotrexate administration schedule and dose in the treatment
      of children and adolescents with B-cell neoplasms: a report of the BFM Group
      Study NHL-BFM95.
AB  - In the Non-Hodgkin Lymphoma-Berlin-Frankfurt-Munster 95 (NHL-BFM95) study, we
      tested by randomization whether for patients with B-cell neoplasms methotrexate
      as intravenous infusion over 4 hours (MTX-4h) is not inferior to, but less toxic
      than, a 24-hour intravenous infusion (MTX-24h). Second, we investigated against
      the historical control of study NHL-BFM90, whether for patients with moderate
      tumor mass MTX can be reduced from 5 g/m(2) to 1 g/m(2). Patients received 2 5
      day therapy courses in risk group R1 (resected), 4 in R2 (lactate dehydrogenase
      [LDH] < 500 U/L), 5 in R3 (LDH > 500 to < 1000 U/L) and 6 in R4 (LDH > 1000 U/L
      and/or central nervous system [CNS] disease). Courses contained MTX 1 g/m(2) in
      R1 + R2 and 5 g/m(2) in R3 + R4. Of 505 patients (April 1996 to March 2001), 364
      were randomized to receive MTX-4h or MTX-24h. Failure-free survival (pFFS, 1
      year) for arm MTX-4h versus MTX-24h, respectively, was 95% +/- 5% (n = 20) versus
      100% (n = 19) in R1, 94% +/- 2% (n = 88) versus 96% +/- 2% (n = 95) in R2, and
      77% +/- 5% (n = 62) versus 93% +/- 3% (n = 69) in R3 +/- R4 (per-protocol
      analysis). Incidence of mucositis grade III/IV was significantly lower with MTX
      4h in all risk groups. For patients in R2, event-free survival (pEFS) was 95% +/-
      2% (n = 222) in NHL-BFM95 (MTX 1 g/m(2)) and 97% +/- 1% (n = 154) in NHL-BFM90
      (MTX 5 g/m(2)). In conclusion, MTX-4h was less toxic than MTX-24h. MTX-4h was
      noninferior to MTX-24h for limited stage B-cell non-Hodgkin lymphoma (B-NHL) but
      not for advanced disease. For limited disease, MTX 1 g/m(2) is noninferior to 5
      g/m(2).

PMID- 15486067
TI  - Activation of the PI3K/mTOR pathway by BCR-ABL contributes to increased
      production of reactive oxygen species.
AB  - BCR-ABL oncoprotein-expressing cells are associated with a relative increase of
      intracellular reactive oxygen species (ROS), which is thought to play a role in
      transformation. Elevated ROS levels in BCR-ABL-transformed cells were found to be
      blocked by the mitochondrial complex I inhibitor rotenone as well as the glucose
      transport inhibitor phloretin, suggesting that the source of increased ROS might
      be related to increased glucose metabolism. The glucose analog 2-deoxyglucose (2
      DOG) reduced ROS to levels found in non-BCR-ABL-transformed cells and inhibited
      cell growth alone or in cooperation with imatinib mesylate (Gleevec). A mutant of
      BCR-ABL that is defective in transformation of myeloid cells, Tyr177Phe, was also
      found to be defective in raising intracellular ROS levels. Glucose metabolism in
      BCR-ABL-transformed cells is likely to be mediated by activation of the
      phosphatidylinositol-3'-kinase (PI3K) pathway, which is regulated through this
      site. Inhibition of PI3K or mTOR led to a significant decrease in ROS levels.
      Overall, our results suggest that elevated levels of ROS in BCR-ABL-transformed
      cells are secondary to a transformation-associated increase in glucose metabolism
      and an overactive mitochondrial electron transport chain and is specifically
      regulated by PI3K. Finally, these results hint at novel targets for drug
      development that may aid traditional therapy.

PMID- 15486068
TI  - Marburg I polymorphism of factor VII-activating protease is associated with
      idiopathic venous thromboembolism.
AB  - The factor VII-activating protease (FSAP) variant Marburg I is known to attenuate
      the profibrinolytic system in vitro and was recently shown to be a significant
      predictor for the evolution and progression of carotid stenosis. The objective of
      this case-control study was to assess FSAP Marburg I's role in the occurrence of
      venous thromboembolism (VTE). The frequency of FSAP Marburg I was significantly
      increased in patients with a history of VTE (17 of 213 patients, 8.0%, P = .014)
      or idiopathic VTE (12 of 103 patients, 11.7%, P = .002) compared to healthy
      controls (5 of 213 controls, 2.3%). Logistic regression analysis confirmed FSAP
      Marburg I to be an independent risk factor for VTE (odds ratio, 3.5; 95%
      confidence interval [CI], 1.2-10.0) and idiopathic VTE (odds ratio, 6.2; 95% CI,
      2.0-18.9).

PMID- 15486069
TI  - Hepcidin is decreased in TFR2 hemochromatosis.
AB  - The hepatic peptide hepcidin is the key regulator of iron metabolism in mammals.
      Recent evidence indicates that certain forms of hereditary hemochromatosis are
      caused by hepcidin deficiency. Juvenile hemochromatosis is associated with
      hepcidin or hemojuvelin mutations, and these patients have low or absent urinary
      hepcidin. Patients with C282Y HFE hemochromatosis also have inappropriately low
      hepcidin levels for the degree of iron loading. The relationship between the
      hemochromatosis due to transferrin receptor 2 (TFR2) mutations and hepcidin was
      unknown. We measured urinary hepcidin levels in 10 patients homozygous for TFR2
      mutations, all with increased transferrin saturation. Urinary hepcidin was low or
      undetectable in 8 of 10 cases irrespective of the previous phlebotomy treatments.
      The only 2 cases with normal hepcidin values had concomitant inflammatory
      conditions. Our data indicate that TFR2 is a modulator of hepcidin production in
      response to iron.

PMID- 15486070
TI  - Binding of beta 2-glycoprotein I to anionic phospholipids facilitates processing
      and presentation of a cryptic epitope that activates pathogenic autoreactive T
      cells.
AB  - Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in
      association with autoantibodies to phospholipid (PL)-binding plasma proteins,
      such as beta(2)-glycoprotein I (beta(2)GPI). We have recently found that CD4(+) T
      cells autoreactive to beta(2)GPI in patients with APS preferentially recognize a
      cryptic peptide encompassing amino acid residues 276-290 (p276-290), which
      contains the major PL-binding site, in the context of DR53. However, it is not
      clear how previously cryptic p276-290 becomes visible to the immune system and
      elicits a pathogenics autoimmune response to beta(2)GPI. Here we show that
      presentation of a disease-relevant cryptic T-cell determinant in beta(2)GPI is
      induced as a direct consequence of antigen processing from beta(2)GPI bound to
      anionic PL. Dendritic cells or macrophages pulsed with PL-bound beta(2)GPI
      induced a response of p276-290-specific CD4(+) T-cell lines generated from the
      patients in an HLA-DR-restricted and antigen-processing-dependent manner but
      those with beta(2)GPI or PL alone did not. In addition, the p276-290-reactive T
      cell response was primed by stimulating peripheral blood T cells from DR53
      carrying healthy individuals with dendritic cells bearing PL-bound beta(2)GPI in
      vitro. Our finding is the first demonstration of an in vitro mechanism eliciting
      pathogenic autoreactive T-cell responses to beta(2)GPI and should be useful in
      clarifying the pathogenesis of APS.

PMID- 15486071
TI  - Comparison of graft-versus-host-disease and survival after HLA-identical sibling
      bone marrow transplantation in ethnic populations.
AB  - The association of ethnicity with the incidence of graft-versus-host disease
      (GVHD) and other clinical outcomes after transplantation is controversial. We
      compared the results of HLA-identical sibling bone marrow transplantations for
      leukemia, performed between 1990 and 1999, among different ethnic populations,
      including 562 Japanese, 829 white Americans, 71 African Americans, 195
      Scandinavians, and 95 Irish. Results for adults and children were analyzed
      separately. Multivariate analyses of adult patients showed that white Americans,
      African Americans, and Irish cohorts were at significantly higher risk for acute
      GVHD than Japanese or Scandinavian cohorts (relative risk [RR] = 1.77, P < .001;
      RR = 1.84, P < .006; RR = 2.22, P < .001, respectively). White Americans, African
      Americans, and Irish, but not Scandinavians, were at significantly higher risk
      for early (within 3 months of transplantation) transplant-related mortality (TRM)
      compared with Japanese (RR = 2.99, P < .001; RR = 5.88, P < .001; RR = 2.66, P <
      .009, respectively). No differences in the risk for chronic GVHD, relapse, and
      overall survival were noted. In the pediatric cohort (limited to Japanese and
      white Americans), white Americans were at significantly higher risk for acute (RR
      = 1.93; P = .04) and chronic (RR = 3.16; P = .002) GVHD. No differences in other
      clinical outcomes were noted. Our findings suggest that ethnicity may influence
      the risk for GVHD, though overall survival rates after transplantation remain
      similar.

PMID- 15486072
TI  - Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara
      C) in relapsed and refractory acute leukemias.
AB  - Clofarabine (2-chloro-2'-fluoro-deoxy-9-beta-D-arabinofuranosyladenine) is a
      second-generation nucleoside analog with activity in acute leukemias. As
      clofarabine is a potent inhibitor of ribonucleotide reductase (RnR), we
      hypothesized that clofarabine will modulate ara-c triphosphate accumulation and
      increase the antileukemic activity of cytarabine (ara-C). We conducted a phase 1
      2 study of clofarabine plus ara-C in 32 patients with relapsed acute leukemia (25
      acute myeloid leukemia [AML], 2 acute lymphoblastic leukemia [ALL]), 4 high-risk
      myelodysplastic syndrome (MDS), and 1 blast-phase chronic myeloid leukemia
      (CML).(1) Clofarabine was given as a 1-hour intravenous infusion for 5 days (days
      2 through 6) followed 4 hours later by ara-C at 1 g/m(2) per day as a 2-hour
      intravenous infusion for 5 days (days 1 through 5). The phase 2 dose of
      clofarabine was 40 mg/m(2) per day for 5 days. Among all patients, 7 (22%)
      achieved complete remission (CR), and 5 (16%) achieved CR with incomplete
      platelet recovery (CRp), for an overall response rate of 38%. No responses
      occurred in 3 patients with ALL and CML. One patient (3%) died during induction.
      Adverse events were mainly less than or equal to grade 2, including transient
      liver test abnormalities, nausea/vomiting, diarrhea, skin rashes, mucositis, and
      palmoplantar erythrodysesthesias. Plasma clofarabine levels generated clofarabine
      triphosphate accumulation, which resulted in an increase in ara-CTP in the
      leukemic blasts. The combination of clofarabine with ara-C is safe and active.
      Cellular pharmacology data support the biochemical modulation strategy.

PMID- 15486073
TI  - Tumor metastasis but not tumor growth is dependent on Src-mediated vascular
      permeability.
AB  - Vascular endothelial growth factor (VEGF)-induced vascular permeability (VP) is a
      hallmark of tumor growth and metastasis. Previous studies have shown a
      requirement for Src kinase in VEGF-mediated VP and signaling in blood vessels. In
      this study, we have examined the effect of Src-mediated reduced VP on tumor
      growth and metastasis. The growth and spontaneous metastasis of VEGF-expressing
      tumor cells were determined in Src-knockout (src(-/-)) or control mice (src(+/+)
      or src(+/-)). In comparison to control mice, src-null mice had a significant
      reduction in tumor-induced VP as well as a subsequent reduction in spontaneous
      metastasis. In contrast, primary tumor weight and vascular density were unchanged
      between src-null and control mice. Consistent with a role for Src in the
      extravasation of tumor cells from the circulation, direct intravenous injection
      of lung carcinoma cells resulted in a more than 2-fold reduction in lung tumor
      burden in src-null mice compared to control mice. The comparison of the results
      from the experimental metastasis and the spontaneous metastasis models suggests
      that there are defects in VP in the primary site of Src-deficient mice and that
      there may be an essential role for Src and Src-mediated VP in tumor metastasis to
      the lung.

PMID- 15486074
TI  - Metabolic activation of fluoropyrrolidine dipeptidyl peptidase-IV inhibitors by
      rat liver microsomes.
AB  - The current study evaluated the potential for two dipeptidyl peptidase-IV (DPP
      IV) inhibitor analogs (1S)-1-(trans-4-([(4
      trifluoromethoxyphenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1
      yl]-2-oxoethanaminium chloride and (1S)-1-(trans-4-([(2,4
      difluorophenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1-yl]-2
      oxoethanaminium chloride (MRL-A and MRL-B), containing a fluoropyrrolidine moiety
      in the structure, to undergo metabolic activation. The irreversible binding of
      these tritium-labeled compounds to rat liver microsomal protein was time- and
      NADPH-dependent and was attenuated by the addition of reduced glutathione (GSH)
      or N-acetylcysteine (NAC) to the incubation, indicating that chemically reactive
      intermediates were formed and trapped by these nucleophiles. Mass spectrometric
      analyses and further trapping experiments with semicarbazide indicated that the
      fluoropyrrolidine ring had undergone sequential oxidation and defluorination
      events resulting in the formation of GSH or NAC conjugates of the pyrrolidine
      moiety. The bioactivation of MRL-A was catalyzed primarily by rat recombinant
      CYP3A1 and CYP3A2. Pretreatment of rats with prototypic CYP3A1 and 3A2 inducers
      (pregnenolone-16alpha-carbonitrile and dexamethasone) enhanced the extent of
      bioactivation which, in turn, led to a higher degree of in vitro irreversible
      binding to microsomal proteins (5- and 9-fold increase, respectively). Herein, we
      describe studies that demonstrate that the fluoropyrrolidine ring is prone to
      metabolic activation and that GSH or NAC can trap the reactive intermediates to
      form adducts that provide insight into the mechanisms of bioactivation.

PMID- 15486075
TI  - Interactions between CYP2C9 and CYP2C19 in reconstituted binary systems influence
      their catalytic activity: possible rationale for the inability of CYP2C19 to
      catalyze methoxychlor demethylation in human liver microsomes.
AB  - Previous studies in our laboratory showed that among cDNA-expressed human
      cytochrome P450 (P450) supersomes, CYP2C19 was the most active in methoxychlor-O
      demethylation. However, based on the lack of inhibition of methoxychlor-O
      demethylation by monoclonal anti-CYP2C19 antibodies in human liver microsomes
      (HLM), CYP2C19 did not seem to catalyze that reaction in HLM. By contrast,
      CYP2C9, much less active than CYP2C19 in supersomes, was the most active in HLM.
      The current study examines whether the lack of methoxychlor-O-demethylation by
      CYP2C19 in HLM was due to CYP2C19 exhibiting inferior competition for the NADPH
      cytochrome P450 reductase (CPR) versus CYP2C9 and explores the interactions
      between CYP2C9 and CYP2C19 in a singular and binary complex of a reconstituted
      system. When reconstituted with CPR, cytochrome b(5), and lipid, purified CYP2C19
      and CYP2C9 catalyzed methoxychlor-O-demethylation. However, whereas equimolar CPR
      to CYP2C9 supported maximal rates of methoxychlor demethylation and diclofenac
      hydroxylation, the rate of methoxychlor demethylation by CYP2C19 was not fully
      saturated, even with a 9-fold molar excess of CPR over CYP2C19. This behavior of
      CYP2C19 was also observed with S-mephenytoin as the substrate. When a binary
      reconstitution system was prepared by mixing CYP2C9 and CYP2C19 enzymes,
      methoxychlor-O-demethylation and S-mephenytoin hydroxylation by CYP2C19 were
      dramatically inhibited. Inhibition depended on the amount of CPR and substrate
      used. By contrast, in the incubation containing CYP2C9, diclofenac hydroxylation
      was activated by the presence of CYP2C19. These results show that interactions
      among P450 enzymes can modulate their catalytic rates, which depend on the
      substrate undergoing metabolism.

PMID- 15486076
TI  - Expression, localization, and function of the carnitine transporter octn2
      (slc22a5) in human placenta.
AB  - L-carnitine is assumed to play an important role in fetal development, and there
      is evidence that carnitine is transported across the placenta. The protein
      involved in this transfer, however, has not been identified on a molecular level.
      We therefore characterized localization and function of the carnitine transporter
      OCTN2 in human placenta. Significant expression of OCTN2 mRNA was detected in
      human placenta applying real-time polymerase chain reaction technology. Confocal
      immunofluorescence microscopy using an antibody directed against the carboxy
      terminus of OCTN2 protein revealed that it is predominantly expressed in the
      apical membrane of syncytiotrophoblasts. This was confirmed by the costaining of
      organic anion-transporting polypeptide B and MRP2, which are known to be
      expressed mainly in the basal and apical syncytiotrophoblasts membrane,
      respectively. To further support this finding, we performed transport studies
      using basal and apical placenta membrane vesicles. We could demonstrate that the
      carnitine uptake into the apical vesicles was about eight times higher compared
      with the basal ones. Moreover, this uptake was sodium- and pH-dependent with an
      apparent K(m) value of 21 muM and inhibited by verapamil, which is in line with
      published data for recombinant OCTN2. Finally, experiments using trophoblasts in
      cell culture revealed that expression of OCTN2 paralleled human
      choriogonadotropin production and thus is modulated by cellular differentiation.
      In summary, we show expression and function of OCTN2 in human placenta. Moreover,
      several lines of evidence indicate that OCTN2 is localized in the apical membrane
      of syncytiotrophoblasts, thereby suggesting a major role in the uptake of
      carnitine during fetal development.

PMID- 15486077
TI  - Metabolism, pharmacokinetics, tissue distribution, and excretion of [14C]CP
      424391 in rats.
AB  - CP-424391, 2-amino-N-[3aR-benzyl-2-methyl-3-oxo-2,3,3a,4,6,7-hexahydro
      pyrazolo[4,3-c]pyridin-5-yl)-1R-benzyloxymethyl-2-oxoethyl]-isobutyramide, is an
      orally active growth hormone secretagogue currently being developed. In this
      study, we investigated the metabolic fate and disposition of radiolabeled CP
      424391 in rats. Following 15 mg/kg single oral administration to Sprague-Dawley
      rats, 91% of the radiolabeled dose was recovered. Feces was the major route of
      excretion: 77% of the dose recovered in feces of the female rat and 84% in the
      male. Excretion in the urine was 15% in the female rat compared with 7% in the
      male. Both fecal and urinary metabolic profiles were consistent in both genders.
      The metabolic pathways of CP-424391 were oxidation at the benzyl group of the O
      benzylserine moiety, N-demethylation of pyrazolidine, and/or O-debenzylation. In
      circulation, CP-424391 was absorbed within the first hour to an average apparent
      C(max) of 1.44 microg/ml. CP-424391 accounts for about 40% of radioactivity area
      under the plasma concentration-time curve and C(max) in circulation. The plasma
      terminal elimination half-life of CP-424391 was 2.4 h and for total radioactivity
      was 2.8 h. The radioactivity was widely distributed in all tissues except for the
      central nervous system. [(14)C]CP-424391 radioactivity was eliminated from most
      tissues by 9 h with the exception of liver, skin, and uvea. By 168 h, [(14)C]CP
      424391 radioactivity remained localized only in the uvea.

PMID- 15486078
TI  - Antimicrobial susceptibility of Haemophilus influenzae strains isolated from
      invasive disease in Italy.
AB  - OBJECTIVES: Haemophilus influenzae invasive disease is potentially life
      threatening and requires prompt antibiotic therapy. The aim of this study was to
      assess the antimicrobial susceptibility of H. influenzae strains isolated from
      invasive disease in Italy and to investigate ampicillin-resistant isolates by
      molecular biology techniques. MATERIALS AND METHODS: One-hundred and seventy-six
      invasive H. influenzae isolates, collected during 1998-2003, were analysed for
      susceptibility to ampicillin, azithromycin, chloramphenicol and ciprofloxacin.
      Ampicillin-resistant isolates were further tested against cefotaxime and
      imipenem. MICs were determined by Etest and interpreted according to NCCLS
      criteria. The ampicillin resistance genes, bla(TEM) and bla(ROB), were searched
      for by PCR. Genetic relatedness among ampicillin-resistant isolates was
      investigated by PFGE. RESULTS: Overall, ampicillin resistance was 10.2% (all beta
      lactamase producer strains). The prevalence of ampicillin-resistant isolates
      increased from 6.9% in 1998/1999 to 19% in 2002/2003. Resistance to azithromycin
      and chloramphenicol was 6.8% and 1.7%, respectively. No strains were resistant to
      ciprofloxacin. Co-resistance between ampicillin and chloramphenicol and between
      ampicillin and azithromycin was observed in three and one isolates, respectively.
      All ampicillin-resistant isolates were susceptible to cefotaxime and imipenem and
      all harboured the bla(TEM) gene. PFGE demonstrated that most of the ampicillin
      resistant isolates showed little genetic homology. CONCLUSIONS: An upward trend
      in resistance to ampicillin due to beta-lactamase production was demonstrated In
      Italy. According to PFGE results, clonal dissemination of ampicillin-resistant
      isolates does not occur. Imipenem may represent an appropriate alternative for
      treatment of H. influenzae invasive disease caused by ampicillin-resistant
      isolates when third-generation cephalosporins cannot be used.

PMID- 15486079
TI  - Treatment of experimental osteomyelitis by liposomal antibiotics.
AB  - OBJECTIVES: Traditional antibiotic therapy of staphylococcal osteomyelitis by a
      single drug or a drug combination is ineffective in producing complete
      sterilization of infected bones. The aim of this study was to develop a non
      traditional delivery system of antibiotics for treatment of chronic experimental
      osteomyelitis. METHODS: In the current work, ciprofloxacin and vancomycin were
      encapsulated in a cationic, anionic or neutral liposomal formulation. For
      prolonged circulation in serum, liposomal dispersions (<100 nm in diameter) were
      sonicated for different times (20, 40, 60 or 80 s), and tested for antibacterial
      activities. RESULTS AND CONCLUSIONS: Liposomes sonicated for 40 s gave the
      highest antibacterial activities in vitro. Since cationic liposomes trapped the
      highest percentage of antibiotics, and enhanced antibacterial activity above that
      of the free drugs, they were used for therapeutic trials to treat chronic
      staphylococcal osteomyelitis induced in rabbits. Therapeutic trials with
      antibiotics given intravenously revealed that, free ciprofloxacin or vancomycin
      given alone for 14 days was ineffective in sterilizing bone. Combination therapy
      with free ciprofloxacin and vancomycin for 14 days was more effective. However,
      this group showed renal dysfunction and severe diarrhoea, which resulted in loss
      of 33.3% of treated animals. Treatment with liposomal forms of either drug for 7
      days was ineffective. Meanwhile, combination therapy in liposomal form for 7 days
      was more effective. Complete sterilization of bone tissues on cultures (100%
      cure) was obtained only in the group treated for 14 days with the combination of
      both drugs in liposomal form. Moreover, liposomal formulations showed much lower
      nephrotoxicity and a lower incidence of severe diarrhoea than that induced by
      free drugs.

PMID- 15486080
TI  - Cefepime and the inoculum effect in tests with Klebsiella pneumoniae producing
      plasmid-mediated AmpC-type beta-lactamase.
AB  - OBJECTIVE: In the past decade, a new problem in Klebsiella pneumoniae strains has
      emerged: plasmid-mediated AmpC enzymes. This study was conducted to investigate
      the activity of cefepime against clinical isolates by determining the activities
      of cefepime and three other parenteral beta-lactam agents in standard and high
      inoculum MIC tests. METHODS: A total of 61 K. pneumoniae blood isolates,
      including 28 isolates producing AmpC-type beta-lactamases (14 isolates of DHA-1
      and 14 isolates of CMY-1-like) and 33 isolates producing extended-spectrum beta
      lactamases (ESBLs) (32 isolates of TEM- or SHV-related and one isolate of CTX-M
      14-like), were included in the study. Antimicrobial susceptibilities were
      determined using broth microdilution MIC tests with standard and 100-fold-higher
      inocula. The inoculum effect was defined as an eight-fold or greater MIC increase
      on testing with the higher inoculum. RESULTS: In tests with AmpC beta-lactamase
      producing K. pneumoniae isolates and their transconjugants, the inoculum effect
      was most consistently detected with cefepime, cefotaxime and ceftazidime, as
      inoculum effects were consistently detected in ESBL-producing isolates. However,
      the inoculum effect was least frequently detected with imipenem. CONCLUSION:
      Although the inoculum effect is an in vitro laboratory phenomenon, these results
      suggest that cefepime may be a less than reliable agent for therapy in cases of
      high inoculum infections caused by AmpC beta-lactamase-producing K. pneumoniae.

PMID- 15486081
TI  - Regulated overexpression of CDR1 in Candida albicans confers multidrug
      resistance.
AB  - OBJECTIVES: Information on the function of Candida albicans ATP-binding cassette
      (ABC) membrane transporter Cdr1p has come from studying the effect of gene
      inactivation in C. albicans and from heterologous Cdr1p expression in the yeast
      Saccharomyces cerevisiae. These approaches, however, give only an indirect
      indication of Cdr1p function in C. albicans itself. The objective of this study
      was to determine Cdr1p function in C. albicans by induced overexpression of Cdr1p
      in a C. albicans CDR1-deleted strain. METHODS: The C. albicans CDR1 open reading
      frame was fused to the C. albicans HEX1 promoter and used to complement a CDR1
      null mutant to create strain FL3. The effect of inducing the FL3 HEX1 promoter,
      by growth on medium containing N-acetylglucosamine (GlcNAc) as the carbon source,
      on CDR1 expression and drug susceptibility was determined. RESULTS: C. albicans
      FL3 cells grown on medium containing GlcNAc overexpressed CDR1 mRNA and a 170 kDa
      plasma membrane protein that reacted with anti-Cdr1p antibodies. Overexpression
      of Cdr1p in C. albicans FL3 conferred resistance to structurally unrelated
      chemicals such as terbinafine, brefeldin A, cerulenin and nigericin as well as to
      azole antifungal agents, but not resistance to polyene antibiotics. FK506,
      ascomycin and ciclosporin A chemosensitized FL3 to fluconazole. FL3 cells grown
      on GlcNAc effluxed 5.3 times as much Cdr1p substrate rhodamine 6G, over a 10 min
      period, as FL3 cells grown on glucose, and this rhodamine 6G efflux was inhibited
      by including fluconazole in the assay. CONCLUSION: This study provides the first
      direct demonstration of Cdr1p pump activity in C. albicans.

PMID- 15486082
TI  - Plasmid-mediated 16S rRNA methylases conferring high-level aminoglycoside
      resistance in Escherichia coli and Klebsiella pneumoniae isolates from two
      Taiwanese hospitals.
AB  - OBJECTIVES: This study was conducted to investigate the occurrence of 16S rRNA
      methylases that confer high-level aminoglycoside resistance in Klebsiella
      pneumoniae and Escherichia coli isolates from two Taiwanese hospitals and the
      characteristics of these isolates. METHODS: A total of 1624 K. pneumoniae and
      2559 E. coli isolates consecutively collected over an 18 month period from a
      university hospital and seven E. coli and eight K. pneumoniae isolates that were
      resistant to amikacin from a district hospital were analysed. Two 16S rRNA
      methylase genes, armA and rmtB, were detected by PCR-based assays. beta-Lactamase
      characteristics were determined by phenotypic and genotypic methods. RESULTS:
      Overall, 28 armA-positive and seven rmtB-positive isolates were identified, and
      extended-spectrum beta-lactamases (ESBLs) were detected in 33 (94.3%) isolates.
      The prevalence rates of armA and rmtB at the university hospital were 0.9% (n=15)
      and 0.3% (n=5) in K. pneumoniae and 0.4% (n=10) and 0.04% (n=1) in E. coli. CTX-M
      3, CTX-M-14, SHV-5-like ESBLs, and CMY-2 were detected alone or in combination in
      21, 6, 11, and 2, respectively, of the 28 armA-positive isolates. CTX-M-14 was
      detected in six of the seven rmtB-positive isolates. Fingerprinting of
      conjugative plasmids revealed the dissemination of closely related plasmids
      containing both armA and bla(CTX-M-3). PFGE suggests that armA and rmtB spread by
      both horizontal transfer and clonal spread. CONCLUSIONS: This is the first report
      of the emergence of 16S rRNA methylases in Enterobacteriaceae in Taiwan. The
      spread of the multidrug-resistant isolates producing both ESBLs and 16S rRNA
      methylases may become a clinical problem.

PMID- 15486083
TI  - Is it safe to use carbapenems in patients with a history of allergy to
      penicillin?
AB  - OBJECTIVES: The purpose of this retrospective study was to ascertain the clinical
      safety of administering carbapenems, namely imipenem/cilastatin and meropenem, in
      patients with a history of penicillin allergy compared with administering
      carbapenems in patients with no reported penicillin allergy. Carbapenems are
      similar in chemical structure to the penicillins and therefore are associated
      with a risk for allergic cross-hypersensitivity. Carbapenems are commonly avoided
      in patients with a reported penicillin allergy on the basis of a potential cross
      hypersensitivity with penicillin, however, very few studies have been conducted
      describing the incidence of cross-hypersensitivity between penicillin and
      carbapenems. METHODS: A retrospective review was conducted in a total of 266
      patients who were administered either imipenem/cilastatin or meropenem. The
      patients were admitted to the Cleveland Clinic Health System--Eastern Region
      Hospitals during the years 2001 and 2002. RESULTS: Fifteen of the 163 patients
      (9.2%) with reported penicillin allergy developed a hypersensitivity reaction to
      meropenem or imipenem/cilastatin whereas 3.9% of the 103 patients without
      penicillin allergy developed a hypersensitivity reaction to meropenem or
      imipenem/cilastatin. These results are not statistically significant.
      CONCLUSIONS: Based on this study and other similar studies, the true incidence of
      cross-hypersensitivity reactions between penicillin and carbapenems may be lower
      than previously reported. Carbapenem use may be reasonable for penicillin
      allergic patients if caution is exercised.

PMID- 15486084
TI  - Pulsatile delivery of amoxicillin against Streptococcus pneumoniae.
AB  - OBJECTIVE: Beta-Lactam antimicrobials are dosed intermittently or continuously
      based on their short half-lives and concentration-independent activity. Based on
      the relationship between antimicrobial killing and bacterial growth cycle, the
      pharmacodynamics of a unique pulsatile strategy was investigated. METHODS: In
      vitro pharmacodynamic models with initial inocula of 6 log(10) cfu/mL were
      utilized to simulate amoxicillin regimens against two Streptococcus pneumoniae
      isolates: 16891 (MIC = 4 mg/L) and ATCC 49150 (MIC = 0.016 mg/L). Time-kill
      profiles of pulsatile dosing of amoxicillin (total daily dose fractionated
      equally and given at 0, 2, 4 and 6 h for each 24 h cycle) were compared with
      regimens of every 8 h and every 12 h with the same 24 h drug exposure. Each
      regimen targeted cumulative peak concentrations of 30, 15 and 5 mg/L for each 24
      h cycle. A t(1/2) of 1 h was simulated for all experiments. Bacterial density was
      quantified over 96 h. RESULTS: Against 16891, every 8 h and every 12 h regimens
      exhibited minimal bacterial kill at all dosing levels. In contrast, pulsatile
      dosing at 30 mg/L/24 h resulted in an initial modest approximately 1 log(10)
      cfu/mL kill with regrowth to growth control levels at 24 h but was immediately
      followed by a rapid approximately 2 log(10) cfu/mL kill by 32 h. This pattern of
      kill and regrowth repeated at the same magnitude for each 24 h cycle for the 96 h
      study duration. Against the susceptible strain (ATCC 49150), both pulse and
      traditional dosing of amoxicillin resulted in rapid and significant kill to our
      detection limits for the entire study duration. A pattern of kill and regrowth
      was only observed at the lowest dose (0.05 mg/L) against ATCC 49150. At
      therapeutic levels, all regimens rapidly achieved undetectable limits against
      this strain for the study duration. No significant alterations in post-exposure
      MICs were noted. Overall bacterial density reduction was similar between the
      regimens for the susceptible isolate and greater with pulsatile regimens against
      the less susceptible strain. CONCLUSION: Pulsatile dosing, which involves
      administration of the total daily dose over the first 6 h of the day, may
      represent a unique and alternative strategy for dosing beta-lactam
      antimicrobials.

PMID- 15486085
TI  - Survival factor-induced extracellular signal-regulated kinase phosphorylates BIM,
      inhibiting its association with BAX and proapoptotic activity.
AB  - The "BH3-only" proapoptotic BCL-2 family members initiate the intrinsic apoptotic
      pathway. A small interfering RNA knockdown of BIM confirms this BH3-only member
      is important for the cytokine-mediated homeostasis of hematopoietic cells. We
      show here that the phosphorylation status of BIM controls its proapoptotic
      activity. IL-3, a hematopoietic survival factor, induces extracellular signal
      regulated kinase/mitogen-activated protein kinase-mediated phosphorylation of BIM
      on three serine sites (S55, S65, and S100). After IL-3 withdrawal, only
      nonphosphorylated BIM interacts with the multidomain proapoptotic effector BAX.
      Phosphorylation of BIM on exposure of cells to IL-3 dramatically reduces the
      BIM/BAX interaction. A nonphosphorylatable BIM molecule (S55A, S65A, and S100A)
      demonstrates enhanced interaction with BAX and enhanced proapoptotic activity.
      Thus, ERK/mitogen-activated protein kinase-dependent phosphorylation of BIM in
      response to survival factor regulates BIM/BAX interaction and the pro-death
      activity of BIM.

PMID- 15486086
TI  - Differential regulation of histone acetylation and generation of mutations in
      switch regions is associated with Ig class switching.
AB  - Class switch recombination (CSR) allows B cells to make effective protective
      antibodies. CSR involves the replacement of the mu constant region with one of
      the downstream constant regions by recombination between the donor and recipient
      switch (S) regions. Although histone H3 hyperacetylation in recipient S regions
      was recently reported to coincide with CSR, the relative histone H3 and H4
      acetylation status of the donor and recipient S regions and the relationship
      between the generation of mutations and histone hyperacetylation in S regions
      have not been addressed. Here we report that histone H3 and H4 were
      constitutively hyperacetylated in the donor Smu region before and after different
      mitogen and cytokine treatments. We observed an increased frequency of mutations
      in hyperacetylated Sgamma DNA segments immunoprecipitated with anti-acetyl
      histone antibodies. Furthermore, time course experiments revealed that the
      pattern of association of RNA polymerase II with S regions was much like that of
      H3 hyperacetylation but not always like that of H4 hyperacetylation.
      Collectively, our data suggest that H3 and H4 histone hyperacetylation in
      different S regions is regulated differently, that RNA polymerase II distribution
      and H3 hyperacetylation reflect the transcriptional activity of a given S region,
      and that transcription, hyperacetylation, and mutation are not sufficient to
      guarantee CSR. These findings support the notion that there are additional
      modifications and/or factors involved in the complex process of CSR.

PMID- 15486087
TI  - Origin of icosahedral symmetry in viruses.
AB  - With few exceptions, the shells (capsids) of sphere-like viruses have the
      symmetry of an icosahedron and are composed of coat proteins (subunits) assembled
      in special motifs, the T-number structures. Although the synthesis of artificial
      protein cages is a rapidly developing area of materials science, the design
      criteria for self-assembled shells that can reproduce the remarkable properties
      of viral capsids are only beginning to be understood. We present here a minimal
      model for equilibrium capsid structure, introducing an explicit interaction
      between protein multimers (capsomers). Using Monte Carlo simulation we show that
      the model reproduces the main structures of viruses in vivo (T-number icosahedra)
      and important nonicosahedral structures (with octahedral and cubic symmetry)
      observed in vitro. Our model can also predict capsid strength and shed light on
      genome release mechanisms.

PMID- 15486088
TI  - The beginnings of mucin biosynthesis: the crystal structure of UDP
      GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferase-T1.
AB  - UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (ppGaNTases)
      initiate the formation of mucin-type, O-linked glycans by catalyzing the transfer
      of alpha-N-acetylgalactosamine from UDP-GalNAc to Ser or Thr residues of core
      proteins to form the Tn antigen (GalNAc-alpha-1-O-Ser/Thr). ppGaNTases are unique
      among glycosyltransferases in containing a C-terminal lectin domain. We present
      the x-ray crystal structure of a ppGaNTase, murine ppGaNTase-T1, and show that it
      folds to form distinct catalytic and lectin domains. The association of the two
      domains forms a large cleft in the surface of the enzyme that contains a Mn2+ ion
      complexed by invariant D209 and H211 of the "DXH" motif and by invariant H344.
      Each of the three potential lectin domain carbohydrate-binding sites (alpha,
      beta, and gamma) is located on the active-site face of the enzyme, suggesting a
      mechanism by which the transferase may accommodate multiple conformations of
      glycosylated acceptor substrates. A model of a mucin 1 glycopeptide substrate
      bound to the enzyme shows that the spatial separation between the lectin alpha
      site and a modeled active site UDP-GalNAc is consistent with the in vitro pattern
      of glycosylation observed for this peptide catalyzed by ppGaNTase-T1. The
      structure also provides a template for the larger ppGaNTase family, and homology
      models of several ppGaNTase isoforms predict dramatically different surface
      chemistries consistent with isoform-selective acceptor substrate recognition.

PMID- 15486089
TI  - Microarray-based rapid cloning of an ion accumulation deletion mutant in
      Arabidopsis thaliana.
AB  - Here we describe the development of a microarray-based mapping strategy to
      rapidly isolate deletion mutant genes. The presented approach is particularly
      useful for mapping mutant genes that are difficult to phenotype. This strategy
      uses masking bulk segregant analysis to mask unrelated deletions, thus allowing
      identification of target deletions by microarray hybridization of pooled genomic
      DNA from both WT and mutant F2 populations. Elemental profiling has proven to be
      a powerful tool for isolation of nutrient and toxic metal accumulation mutants in
      Arabidopsis. Using microarray mapping, a sodium overaccumulation mutant FN1148
      was identified as having a 523-bp genomic deletion within the second exon and
      intron of the AtHKT1 gene. Further cosegregation, complementation, and
      comparative analyses among different salt-sensitive mutants confirmed that the
      deletion within the AtHKT1 gene is responsible for the sodium overaccumulation in
      shoots and leaf sodium sensitivity of the FN1148 mutant. These results
      demonstrate that microarray-based cloning is an efficient and powerful tool to
      rapidly clone ion accumulation or other genetic deletion mutants that are
      otherwise difficult to phenotype for mapping, such as metabolic or cell signaling
      mutants.

PMID- 15486090
TI  - Complete absence of Cockayne syndrome group B gene product gives rise to UV
      sensitive syndrome but not Cockayne syndrome.
AB  - UV-sensitive syndrome (UVsS) is a rare autosomal recessive disorder characterized
      by photosensitivity and mild freckling but without neurological abnormalities or
      skin tumors. UVsS cells show UV hypersensitivity and defective transcription
      coupled DNA repair of UV damage. It was suggested that UVsS does not belong to
      any complementation groups of known photosensitive disorders such as xeroderma
      pigmentosum and Cockayne syndrome (CS). To identify the gene responsible for
      UVsS, we performed a microcell-mediated chromosome transfer based on the
      functional complementation of UV hypersensitivity. We found that one of the UVsS
      cell lines, UVs1KO, acquired UV resistance when human chromosome 10 was
      transferred. Because the gene responsible for CS group B (CSB), which involves
      neurological abnormalities and photosensitivity as well as a defect in
      transcription-coupled DNA repair of UV damage, is located on chromosome 10, we
      sequenced the CSB gene from UVs1KO and detected a homozygous null mutation. Our
      results indicate that previous complementation analysis of UVs1KO was erroneous.
      This finding was surprising because a null mutation of the CSB gene would be
      expected to result in CS features such as severe developmental and neurological
      abnormalities. On the other hand, no mutation in the CSB cDNA and a normal amount
      of CSB protein was detected in Kps3, a UVsS cell line obtained from an unrelated
      patient, indicating genetic heterogeneity in UVsS. Possible explanations for the
      discrepancy in the genotype-phenotype relationship in UVs1KO are presented.

PMID- 15486091
TI  - Neuronal nitric oxide synthase negatively regulates xanthine oxidoreductase
      inhibition of cardiac excitation-contraction coupling.
AB  - Although interactions between superoxide (O(2)(.-)) and nitric oxide underlie
      many physiologic and pathophysiologic processes, regulation of this crosstalk at
      the enzymatic level is poorly understood. Here, we demonstrate that xanthine
      oxidoreductase (XOR), a prototypic superoxide O(2)(.-) -producing enzyme, and
      neuronal nitric oxide synthase (NOS1) coimmunoprecipitate and colocalize in the
      sarcoplasmic reticulum of cardiac myocytes. Deficiency of NOS1 (but not
      endothelial NOS, NOS3) leads to profound increases in XOR-mediated O(2)(.-)
      production, which in turn depresses myocardial excitation-contraction coupling in
      a manner reversible by XOR inhibition with allopurinol. These data demonstrate a
      unique interaction between a nitric oxide and an O(2)(.-) -generating enzyme that
      accounts for crosstalk between these signaling pathways; these findings
      demonstrate a direct antioxidant mechanism for NOS1 and have pathophysiologic
      implications for the growing number of disease states in which increased XOR
      activity plays a role.

PMID- 15486092
TI  - De novo design of defined helical bundles in membrane environments.
AB  - Control of structure and function in membrane proteins remains a formidable
      challenge. We report here a new design paradigm for the self-assembly of protein
      components in the context of nonpolar environments of biological membranes. An
      incrementally staged assembly process relying on the unique properties of
      fluorinated amino acids was used to drive transmembrane helix-helix interactions.
      In the first step, hydrophobic peptides partitioned into micellar lipids.
      Subsequent phase separation of simultaneously hydrophobic and lipophobic
      fluorinated helical surfaces fueled spontaneous self-assembly of higher order
      oligomers. The creation of these ordered transmembrane protein ensembles is
      supported by gel electrophoresis, circular dichroism spectroscopy, equilibrium
      analytical ultracentrifugation, and fluorescence resonance energy transfer.

PMID- 15486093
TI  - Functional coupling of intracellular calcium and inactivation of voltage-gated
      Kv1.1/Kvbeta1.1 A-type K+ channels.
AB  - Voltage-gated Kv1.1/Kvbeta1.1 A-type channels, as a natural complex, can switch
      from fast to slow inactivation under oxidation/reduction conditions. The mode
      switching of inactivation, which is mediated by a cysteine residue in the
      inactivation ball domain of the Kvbeta1.1 N terminus, can regulate membrane
      electrical excitability. In the present study, we identified a mechanism whereby
      inactivation in Kv1.1/Kvbeta1.1 channels is regulated by calcium influx. The rise
      in intracellular calcium, due to either influx from extracellular space or
      release from intracellular stores, eliminates fast inactivation induced by
      Kvbeta1.1, resulting in slower inactivation and increased steady-state current.
      This oxidation-independent calcium effect is mediated through the Kvbeta1.1 N
      terminus, not the C terminus. We propose that a coupling between calcium influx
      and inactivation of voltage-gated A-type K+ channels occurs as a result of
      membrane depolarization and may contribute to afterhyperpolarization as negative
      feedback to control neuronal excitability.

PMID- 15486094
TI  - Brain region-dependent effects of dexamethasone on counterregulatory responses to
      hypoglycemia in conscious rats.
AB  - The aim of this study was to determine whether activation of central type II
      glucocorticoid receptors can blunt autonomic nervous system counterregulatory
      responses to subsequent hypoglycemia. Sixty conscious unrestrained Sprague-Dawley
      rats were studied during 2-day experiments. Day 1 consisted of either two
      episodes of clamped 2-h hyperinsulinemic (30 pmol x kg(-1) x min(-1))
      hypoglycemia (2.8 +/- 0.1 mM; n = 12), hyperinsulinemic euglycemia (6.2 +/- 0.1
      mM; n = 12), hyperinsulinemic euglycemia plus simultaneous lateral
      cerebroventricular infusion of saline (24 microl/h; n = 8), or hyperinsulinemic
      euglycemia plus either lateral cerebral ventricular infusion (n = 8; LV-DEX
      group), fourth cerebral ventricular (n = 10; 4V-DEX group), or peripheral (n =
      10; P-DEX group) infusion of dexamethasone (5 microg/h), a specific type II
      glucocorticoid receptor analog. For all groups, day 2 consisted of a 2-h
      hyperinsulinemic (30 pmol x kg(-1) x min(-1)) or hypoglycemic (2.9 +/- 0.2 mM)
      clamp. The hypoglycemic group had blunted epinephrine, glucagon, and endogenous
      glucose production in response to subsequent hypoglycemia. Consequently, the
      glucose infusion rate to maintain the glucose levels was significantly greater in
      this group vs. all other groups. The LV-DEX group did not have blunted
      counterregulatory responses to subsequent hypoglycemia, but the P-DEX and 4V-DEX
      groups had significantly lower epinephrine and norepinephrine responses to
      hypoglycemia compared with all other groups. In summary, peripheral and fourth
      cerebral ventricular but not lateral cerebral ventricular infusion of
      dexamethasone led to significant blunting of autonomic counterregulatory
      responses to subsequent hypoglycemia. These data suggest that prior activation of
      type II glucocorticoid receptors within the hindbrain plays a major role in
      blunting autonomic nervous system counterregulatory responses to subsequent
      hypoglycemia in the conscious rat.

PMID- 15486095
TI  - Hypoxia accelerates nitric oxide-dependent inhibition of mitochondrial complex I
      in activated macrophages.
AB  - Excess production of nitric oxide (NO) is implicated in the development of
      multiple organ failure, with a putative mechanism involving direct mitochondrial
      inhibition, predominantly affecting complex I. The persistent effects of NO on
      complex I may be mediated through S-nitrosylation and/or nitration. The temporal
      contribution of these chemical modifications to the inhibition of respiration and
      the influence of concurrent hypoxia have not been previously examined. We
      therefore addressed these questions using J774 macrophages activated by endotoxin
      and interferon-gamma over a 24-h period, incubated at 21% and 1% oxygen. Oxygen
      consumption and complex I activity fell progressively over time in the activated
      cells. This was largely prevented by coincubation with the nonspecific NO
      synthase inhibitor L-N5-(1-iminoethyl)-ornithine. Addition of glutathione ethyl
      ester reversed the inhibition at initial time points, suggesting an early
      mechanism involving nitrosylation. Thereafter, the inhibition of complex I became
      more persistent, coinciding with a progressive increase in mitochondrial
      nitration. Hypoxia accelerated the persistent inhibition of complex I, despite a
      reduction in the total amount of NO generated. Our results suggest that hypoxia
      amplified the mitochondrial inhibition induced by NO generated during
      inflammatory disease states.

PMID- 15486096
TI  - Analysis of bidirectional pattern synchrony of concentration-secretion pairs:
      implementation in the human testicular and adrenal axes.
AB  - The hypothalamo-pituitary-testicular and hypothalamo-pituitary-adrenal axes are
      prototypical coupled neuroendocrine systems. In the present study, we contrasted
      in vivo linkages within and between these two axes using methods without
      linearity assumptions. We examined 11 young (21-31 yr) and 8 older (62-74 yr) men
      who underwent frequent (every 2.5 min) blood sampling overnight for paired
      measurement of LH and testosterone and 35 adults (17 women and 18 men; 26-77 yr
      old) who underwent adrenocorticotropic hormone (ACTH) and cortisol measurements
      every 10 min for 24 h. To mirror physiological interactions, hormone secretion
      was first deconvolved from serial concentrations with a waveform-independent
      biexponential elimination model. Feedforward synchrony, feedback synchrony, and
      the difference in feedforward-feedback synchrony were quantified by the cross
      approximate entropy (X-ApEn) statistic. These were applied in a forward (LH
      concentration template, examining pattern recurrence in testosterone secretion),
      reverse (testosterone concentration template, examining pattern recurrence in LH
      secretion), and differential (forward minus reverse) manner, respectively.
      Analogous concentration-secretion X-ApEn estimates were calculated from ACTH
      cortisol pairs. X-ApEn, a scale- and model-independent measure of pattern
      reproducibility, disclosed 1) greater testosterone-LH feedback coordination than
      LH-testosterone feedforward synchrony in healthy men and significant and
      symmetric erosion of both feedforward and feedback linkages with aging; 2) more
      synchronous ACTH concentration-dependent feedforward than feedback drive of
      cortisol secretion, independent of gender and age; and 3) enhanced detection of
      bidirectional physiological regulation by in vivo pairwise concentration
      secretion compared with concentration-concentration analyses. The linking of
      relevant biological input to output signals and vice versa should be useful in
      the dissection of the reciprocal control of neuroendocrine systems or even in the
      analysis of other nonendocrine networks.

PMID- 15486097
TI  - Antisense transcript and RNA processing alterations suppress instability of
      polyadenylated mRNA in chlamydomonas chloroplasts.
AB  - In chloroplasts, the control of mRNA stability is of critical importance for
      proper regulation of gene expression. The Chlamydomonas reinhardtii strain
      Delta26pAtE is engineered such that the atpB mRNA terminates with an mRNA
      destabilizing polyadenylate tract, resulting in this strain being unable to
      conduct photosynthesis. A collection of photosynthetic revertants was obtained
      from Delta26pAtE, and gel blot hybridizations revealed RNA processing alterations
      in the majority of these suppressor of polyadenylation (spa) strains, resulting
      in a failure to expose the atpB mRNA 3' poly(A) tail. Two exceptions were spa19
      and spa23, which maintained unusual heteroplasmic chloroplast genomes. One genome
      type, termed PS+, conferred photosynthetic competence by contributing to the
      stability of atpB mRNA; the other, termed PS-, was required for viability but
      could not produce stable atpB transcripts. Based on strand-specific RT-PCR, S1
      nuclease protection, and RNA gel blots, evidence was obtained that the PS+ genome
      stabilizes atpB mRNA by generating an atpB antisense transcript, which attenuates
      the degradation of the polyadenylated form. The accumulation of double-stranded
      RNA was confirmed by insensitivity of atpB mRNA from PS+ genome-containing cells
      to S1 nuclease digestion. To obtain additional evidence for antisense RNA
      function in chloroplasts, we used strain Delta26, in which atpB mRNA is unstable
      because of the lack of a 3' stem-loop structure. In this context, when a 121
      nucleotide segment of atpB antisense RNA was expressed from an ectopic site, an
      elevated accumulation of atpB mRNA resulted. Finally, when spa19 was placed in a
      genetic background in which expression of the chloroplast exoribonuclease
      polynucleotide phosphorylase was diminished, the PS+ genome and the antisense
      transcript were no longer required for photosynthesis. Taken together, our
      results suggest that antisense RNA in chloroplasts can protect otherwise unstable
      transcripts from 3'-->5' exonuclease activity, a phenomenon that may occur
      naturally in the symmetrically transcribed and densely packed chloroplast genome.

PMID- 15486098
TI  - Novel targeting signals mediate the sorting of different isoforms of the tail
      anchored membrane protein cytochrome b5 to either endoplasmic reticulum or
      mitochondria.
AB  - Tail-anchored membrane proteins are a class of proteins that are targeted
      posttranslationally to various organelles and integrated by a single segment of
      hydrophobic amino acids located near the C terminus. Although the localization of
      tail-anchored proteins in specific subcellular compartments in plant cells is
      essential for their biological function, the molecular targeting signals
      responsible for sorting these proteins are not well defined. Here, we describe
      the biogenesis of four closely related tung (Aleurites fordii) cytochrome b5
      isoforms (Cb5-A, -B, -C, and -D), which are small tail-anchored proteins that
      play an essential role in many cellular processes, including lipid biosynthesis.
      Using a combination of in vivo and in vitro assays, we show that Cb5-A, -B, and 
      C are targeted exclusively to the endoplasmic reticulum (ER), whereas Cb5-D is
      targeted specifically to mitochondrial outer membranes. Comprehensive mutational
      analyses of ER and mitochondrial Cb5s revealed that their C termini, including
      transmembrane domains (TMD) and tail regions, contained several unique
      physicochemical and sequence-specific characteristics that defined organelle
      specific targeting motifs. Mitochondrial targeting of Cb5 was mediated by a
      combination of hydrophilic amino acids along one face of the TMD, an enrichment
      of branched beta-carbon-containing residues in the medial portion of the TMD, and
      a dibasic -R-R/K/H-x motif in the C-terminal tail. By contrast, ER targeting of
      Cb5 depended primarily upon the overall length and hydrophobicity of the TMD,
      although an -R/H-x-Y/F- motif in the tail was also a targeting determinant.
      Collectively, the results presented provide significant insight into the early
      biogenetic events required for entry of tail-anchored proteins into either the ER
      or mitochondrial targeting pathways.

PMID- 15486099
TI  - The Arabidopsis CSN5A and CSN5B subunits are present in distinct COP9 signalosome
      complexes, and mutations in their JAMM domains exhibit differential dominant
      negative effects on development.
AB  - The COP9 signalosome (CSN) is an evolutionarily conserved multisubunit protein
      complex involved in a variety of signaling and developmental processes through
      the regulation of protein ubiquitination and degradation. A known biochemical
      role attributed to CSN is a metalloprotease activity responsible for the
      derubylation of cullins, core components for several types of ubiquitin E3
      ligases. The CSN's derubylation catalytic center resides in its subunit 5, which
      in Arabidopsis thaliana is encoded by two homologous genes, CSN5A and CSN5B.
      Here, we show that CSN5A and CSN5B subunits are assembled into distinct CSN
      complexes in vivo, which are present in drastically different abundances, with
      CSN(CSN5A) appearing to be the dominant one. Transgenic CSN5A and CSN5B proteins
      carrying a collection of single mutations in or surrounding the metalloprotease
      catalytic center are properly assembled into CSN complexes, but only mutations in
      CSN5A result in a pleiotropic dominant negative phenotype. The extent of
      phenotypic effects caused by mutations in CSN5A is reflected at the molecular
      level by impairment in Cullin1 derubylation. These results reveal that three key
      metal binding residues as well as two other amino acids outside the catalytic
      center play important roles in CSN derubylation activity. Taken together, our
      data provide physiological evidence on a positive role of CSN in the regulation
      of Arabidopsis SCF (for Skp1-Cullin-F-box) E3 ligases through RUB (for Related to
      Ubiquitin) deconjugation and highlight the unequal role that CSN(CSN5A) and
      CSN(CSN5B) play in controlling the cellular derubylation of cullins. The initial
      characterization of CSN5A and CSN5B insertion mutants further supports these
      findings and provides genetic evidence on their unequal role in plant
      development.

PMID- 15486100
TI  - A novel molecular recognition motif necessary for targeting photoactivated
      phytochrome signaling to specific basic helix-loop-helix transcription factors.
AB  - The phytochrome (phy) family of sensory photoreceptors (phyA to phyE) in
      Arabidopsis thaliana control plant developmental transitions in response to
      informational light signals throughout the life cycle. The photoactivated
      conformer of the photoreceptor Pfr has been shown to translocate into the nucleus
      where it induces changes in gene expression by an unknown mechanism. Here, we
      have identified two basic helix-loop-helix (bHLH) transcription factors,
      designated PHYTOCHROME-INTERACTING FACTOR5 (PIF5) and PIF6, which interact
      specifically with the Pfr form of phyB. These two factors cluster tightly with
      PIF3 and two other phy-interacting bHLH proteins in a phylogenetic subfamily
      within the large Arabidopsis bHLH (AtbHLH) family. We have identified a novel
      sequence motif (designated the active phytochrome binding [APB] motif) that is
      conserved in these phy-interacting AtbHLHs but not in other noninteractors. Using
      the isolated domain and site-directed mutagenesis, we have shown that this motif
      is both necessary and sufficient for binding to phyB. Transgenic expression of
      the native APB-containing AtbHLH protein, PIF4, in a pif4 null mutant, rescued
      the photoresponse defect in this mutant, whereas mutated PIF4 constructs with
      site-directed substitutions in conserved APB residues did not. These data
      indicate that the APB motif is necessary for PIF4 function in light-regulated
      seedling development and suggest that conformer-specific binding of phyB to PIF4
      via the APB motif is necessary for this function in vivo. Binding assays with the
      isolated APB domain detected interaction with phyB, but none of the other four
      Arabidopsis phys. Collectively, the data suggest that the APB domain provides a
      phyB-specific recognition module within the AtbHLH family, thereby conferring
      photoreceptor target specificity on a subset of these transcription factors and,
      thus, the potential for selective signal channeling to segments of the
      transcriptional network.

PMID- 15486101
TI  - The plant-specific kinase CDKF;1 is involved in activating phosphorylation of
      cyclin-dependent kinase-activating kinases in Arabidopsis.
AB  - Cyclin-dependent kinases (CDKs) play essential roles in coordinate control of
      cell cycle progression. Activation of CDKs requires interaction with specific
      cyclin partners and phosphorylation of their T-loops by CDK-activating kinases
      (CAKs). The Arabidopsis thaliana genome encodes four potential CAKs. CAK2At
      (CDKD;3) and CAK4At (CDKD;2) are closely related to the vertebrate CAK,
      CDK7/p40MO15; they interact with cyclin H and phosphorylate CDKs, as well as the
      C-terminal domain (CTD) of the largest subunit of RNA polymerase II. CAK1At
      (CDKF;1) shows cyclin H-independent CDK-kinase activity and can activate a
      heterologous CAK, Mcs6, in fission yeast. In Arabidopsis, CAK1At is a subunit of
      a protein complex of 130 kD, which phosphorylates the T-loop of CAK2At and CAK4At
      and activates the CTD-kinase activity of CAK4At in vitro and in root protoplasts.
      These results suggest that CAK1At is a novel CAK-activating kinase that modulates
      the activity of CAK2At and CAK4At, thereby controlling CDK activities and basal
      transcription in Arabidopsis.

PMID- 15486102
TI  - PIL5, a phytochrome-interacting basic helix-loop-helix protein, is a key negative
      regulator of seed germination in Arabidopsis thaliana.
AB  - The first decision made by an angiosperm seed, whether to germinate or not, is
      based on integration of various environmental signals such as water and light.
      The phytochromes (Phys) act as red and far-red light (Pfr) photoreceptors to
      mediate light signaling through yet uncharacterized pathways. We report here that
      the PIF3-like 5 (PIL5) protein, a basic helix-loop-helix transcription factor, is
      a key negative regulator of phytochrome-mediated seed germination. PIL5
      preferentially interacts with the Pfr forms of Phytochrome A (PhyA) and
      Phytochrome B (PhyB). Analyses of a pil5 mutant in conjunction with phyA and phyB
      mutants, a pif3 pil5 double mutant, and PIL5 overexpression lines indicate that
      PIL5 is a negative factor in Phy-mediated promotion of seed germination,
      inhibition of hypocotyl negative gravitropism, and inhibition of hypocotyl
      elongation. Our data identify PIL5 as the first Phy-interacting protein that
      regulates seed germination.

PMID- 15486103
TI  - TELOMERASE ACTIVATOR1 induces telomerase activity and potentiates responses to
      auxin in Arabidopsis.
AB  - Telomerase activity is highly regulated, abundant in rapidly dividing cells and
      reproductive organs, but undetectable in most other differentiated tissues.
      Little is known about mechanisms that regulate telomerase. Here, we used a
      biochemical assay to screen activation-tagged lines of Arabidopsis thaliana for
      mutants that ectopically express this enzyme in their leaves. In one such mutant,
      a previously uncharacterized zinc-finger protein we designate TELOMERASE
      ACTIVATOR1 (TAC1) is overexpressed and induces telomerase in fully differentiated
      leaves without stimulating progression through the cell cycle. Reducing
      endogenous concentrations of auxin in the mutant blocks the ability of TAC1 to
      induce telomerase. This result, along with other phenotypes of the mutant, such
      as the ability of cells to grow in culture without exogenous auxin and increased
      sensitivity of primary root growth to exogenous auxin, indicates that TAC1 not
      only is part of the previously reported link between auxin and telomerase
      expression but also potentiates other classic responses to this phytohormone.

PMID- 15486104
TI  - Structure-function analysis of the presumptive Arabidopsis auxin permease AUX1.
AB  - We have investigated the subcellular localization, the domain topology, and the
      amino acid residues that are critical for the function of the presumptive
      Arabidopsis thaliana auxin influx carrier AUX1. Biochemical fractionation
      experiments and confocal studies using an N-terminal yellow fluorescent protein
      (YFP) fusion observed that AUX1 colocalized with plasma membrane (PM) markers.
      Because of its PM localization, we were able to take advantage of the steep pH
      gradient that exists across the plant cell PM to investigate AUX1 topology using
      YFP as a pH-sensitive probe. The YFP-coding sequence was inserted in selected
      AUX1 hydrophilic loops to orient surface domains on either apoplastic or
      cytoplasmic faces of the PM based on the absence or presence of YFP fluorescence,
      respectively. We were able to demonstrate in conjunction with helix prediction
      programs that AUX1 represents a polytopic membrane protein composed of 11
      transmembrane spanning domains. In parallel, a large aux1 allelic series
      containing null, partial-loss-of-function, and conditional mutations was
      characterized to identify the functionally important domains and amino acid
      residues within the AUX1 polypeptide. Whereas almost all partial-loss-of-function
      and null alleles cluster in the core permease region, the sole conditional allele
      aux1-7 modifies the function of the external C-terminal domain.

PMID- 15486105
TI  - Optimization and evolution of light harvesting in photosynthesis: the role of
      antenna chlorophyll conserved between photosystem II and photosystem I.
AB  - The efficiency of oxygenic photosynthesis depends on the presence of core antenna
      chlorophyll closely associated with the photochemical reaction centers of both
      photosystem II (PSII) and photosystem I (PSI). Although the number and overall
      arrangement of these chlorophylls in PSII and PSI differ, structural comparison
      reveals a cluster of 26 conserved chlorophylls in nearly identical positions and
      orientations. To explore the role of these conserved chlorophylls within PSII and
      PSI we studied the influence of their orientation on the efficiency of
      photochemistry in computer simulations. We found that the native orientations of
      the conserved chlorophylls were not optimal for light harvesting in either
      photosystem. However, PSII and PSI each contain two highly orientationally
      optimized antenna chlorophylls, located close to their respective reaction
      centers, in positions unique to each photosystem. In both photosystems the
      orientation of these optimized bridging chlorophylls had a much larger impact on
      photochemical efficiency than the orientation of any of the conserved
      chlorophylls. The differential optimization of antenna chlorophyll is discussed
      in the context of competing selection pressures for the evolution of light
      harvesting in photosynthesis.

PMID- 15486107
TI  - Massive pulmonary artery thrombosis with haemoptysis in adults with Eisenmenger's
      syndrome: a clinical dilemma.
AB  - Although the frequency of haemoptysis in Eisenmenger's syndrome is well
      recognised, the high prevalence of pulmonary artery thrombus has been newly
      appreciated through the growing use of non-invasive imaging. Three patients with
      Eisenmenger's syndrome with haemoptysis are reported who underwent computed
      tomography pulmonary angiography and cardiovascular magnetic resonance. Each
      patient was found to have aneurysmal dilatation of the right pulmonary artery
      with large laminar thrombus. These cases illustrate a rising clinical problem in
      this special population-that is, how to treat and prevent large pulmonary artery
      thrombosis in the setting of haemoptysis. The authors discuss their approach to
      these cases and the known literature.

PMID- 15486106
TI  - A gene regulatory network model for cell-fate determination during Arabidopsis
      thaliana flower development that is robust and recovers experimental gene
      expression profiles.
AB  - Flowers are icons in developmental studies of complex structures. The vast
      majority of 250,000 angiosperm plant species have flowers with a conserved organ
      plan bearing sepals, petals, stamens, and carpels in the center. The
      combinatorial model for the activity of the so-called ABC homeotic floral genes
      has guided extensive experimental studies in Arabidopsis thaliana and many other
      plant species. However, a mechanistic and dynamical explanation for the ABC model
      and prevalence among flowering plants is lacking. Here, we put forward a simple
      discrete model that postulates logical rules that formally summarize published
      ABC and non-ABC gene interaction data for Arabidopsis floral organ cell fate
      determination and integrates this data into a dynamic network model. This model
      shows that all possible initial conditions converge to few steady gene activity
      states that match gene expression profiles observed experimentally in primordial
      floral organ cells of wild-type and mutant plants. Therefore, the network
      proposed here provides a dynamical explanation for the ABC model and shows that
      precise signaling pathways are not required to restrain cell types to those found
      in Arabidopsis, but these are rather determined by the overall gene network
      dynamics. Furthermore, we performed robustness analyses that clearly show that
      the cell types recovered depend on the network architecture rather than on
      specific values of the model's gene interaction parameters. These results support
      the hypothesis that such a network constitutes a developmental module, and hence
      provide a possible explanation for the overall conservation of the ABC model and
      overall floral plan among angiosperms. In addition, we have been able to predict
      the effects of differences in network architecture between Arabidopsis and
      Petunia hybrida.

PMID- 15486108
TI  - Left atrial phaeochromocytoma.
AB  - Phaeochromocytomas of the heart are very rare. This report describes the case of
      a 69 year old woman presenting with persistent hypertension and a left atrial
      phaeochromocytoma diagnosed by 131I-metaiodobenzylguanidine scintigraphy
      scanning. She was successfully treated by surgical excision with the aid of
      cardiopulmonary bypass and perioperative alpha and beta adrenergic blockade.

PMID- 15486109
TI  - Is informed consent possible in acute myocardial infarction?

PMID- 15486110
TI  - Evaluation of hibernating myocardium.

PMID- 15486111
TI  - Safety of cardiovascular magnetic resonance in patients with cardiovascular
      implants and devices.

PMID- 15486112
TI  - How should we assess patent foramen ovale?

PMID- 15486113
TI  - Seagulls flying in the echo lab.

PMID- 15486114
TI  - Autonomic changes in patients with heart failure and in post-myocardial
      infarction patients.
AB  - A range of techniques for the assessment of autonomic tone are described.
      Impaired baroreflex control of heart period, measured in terms of heart rate
      variability or baroreflex sensitivity, is independently associated with adverse
      prognosis in patients with heart failure and following acute myocardial
      infarction. These techniques have not yet entered routine clinical practice.

PMID- 15486115
TI  - Acute type A aortic dissection in a cardiac allograft recipient: case report and
      review of the literature.
AB  - Dissection of the ascending aorta is uncommon in cardiac allograft recipients and
      usually affects the native aorta. The diagnosis is often made at necropsy. The
      first case is reported of a Bentall procedure performed in a heart transplant
      recipient who presented with ascending aortic dissection of the donor aorta and
      concomitant aortic regurgitation seven years after orthotopic transplantation.

PMID- 15486116
TI  - Warfarin for non-rheumatic atrial fibrillation: five year experience in a
      district general hospital.
AB  - OBJECTIVES: To assess the long term efficacy of and risks associated with
      computer aided oral anticoagulation for non-rheumatic atrial fibrillation (NRAF)
      in a district hospital setting. DESIGN: Retrospective, age stratified, event
      driven clinical database analysis. SETTING: District general hospital.
      PARTICIPANTS: 739 patients receiving warfarin for NRAF between 1996 and 2001.
      Patients were selected from an anticoagulation database through appropriate
      filter settings. MAIN OUTCOME MEASURES: Anticoagulation control (international
      normalised ratio (INR)) and hospitalisations for bleeding complications,
      thromboembolic events, and stroke. RESULTS: Over 1484 patient-years, computer
      assisted anticoagulation was uncontrolled in 38.3% of patients (INR < 2.0 or >
      3.0). No significant differences in INR control were observed with respect to
      patient age (< 65, 65-75, and > 75 years), although to achieve adequate control
      of anticoagulation, the frequency of testing increased significantly with age.
      Annual risks of bleeding complications, thromboembolism, and stroke were 0.76%,
      0.35%, and 0.84%, respectively. No significant differences in these events were
      observed between the three age groups studied. Patients who had thromboembolic
      events and haemorrhagic complications were significantly more likely to have been
      under-anticoagulated (INR < 2.0) and over-anticoagulated (INR > 3.0),
      respectively, at the time of their clinical event. CONCLUSIONS: Computerised long
      term oral anticoagulation for NRAF in a community setting of elderly and diverse
      patients is safe and effective. Anticoagulation control, bleeding events,
      thromboembolic episodes, and stroke rates are directly comparable with those
      reported in major clinical trials. The authors therefore support the strategy of
      rate control with long term oral anticoagulation for NRAF in general clinical
      practice.

PMID- 15486117
TI  - Sudden unexpected death in heart failure may be preceded by short term,
      intraindividual increases in inflammation and in autonomic dysfunction: a pilot
      study.
AB  - OBJECTIVE: To see whether sudden unexpected death in chronic heart failure is
      preceded by intraindividual worsening in inflammation and in ECG criteria. DESIGN
      AND SETTING: Prospective cohort study conducted in the community. PATIENTS: 34
      patients with chronic heart failure were studied. Their mean (SD) age was 68 (8)
      years, 29 were men, mean (SD) left ventricular ejection fraction was 29 (9)%, and
      they were in New York Heart Association functional class II (n = 20), III (n =
      11), and IV (n = 3). The patients were examined monthly over 24 months, with
      sequential measurement of C reactive protein and neutrophil counts and 24 hour
      ambulatory ECG monitoring measuring heart rate variability, mean heart rate, and
      arrhythmias. Intraindividual changes in these parameters were related to
      subsequent cardiac deaths. RESULTS: During follow up, nine patients died: five
      patients had a sudden unexpected death (SUD) and four died of progressive heart
      failure (PHF). There were significant intraindividual changes in neutrophil
      counts (p = 0.02), C reactive protein (p = 0.039), and heart rate variability (p
      < or = 0.018) in those who died of SUD and PHF. In contrast no significant
      changes were seen in ventricular extrasystoles, ventricular tachycardia episodes,
      brain natriuretic peptide, or aldosterone in the SUD group, but all of these
      parameters did increase as expected in those who died of PHF. CONCLUSIONS: This
      is preliminary evidence that SUD may be preceded by intraindividual increases in
      both inflammation and autonomic dysfunction. Both may be causal in genesis but,
      even if they are not, intraindividual increases in either may be convenient
      markers to identify patients at high risk of impending SUD. Larger studies are
      needed to confirm the observation from this pilot study.

PMID- 15486118
TI  - Paradox of circulating advanced glycation end product concentrations in patients
      with congestive heart failure and after heart transplantation.
AB  - OBJECTIVES: To analyse circulating concentrations of advanced glycation end
      products (AGEs) in patients with severe congestive heart failure (CHF) and after
      heart transplantation; to identify the potential contribution of kidney function
      to plasma AGE concentrations; and to determine whether AGE concentrations and
      parameters of oxidative stress are interrelated. METHODS AND RESULTS: Circulating
      N(epsilon)-(carboxymethyl)lysine (CML) and AGE associated fluorescence (AGE-Fl),
      lipid peroxidation, and glomerular filtration rate (GFR) were measured in a cross
      sectional study of 22 patients with advanced CHF, 30 heart transplant recipients,
      and 20 healthy controls. Compared with the controls, the CHF patients had
      decreased CML (mean (SEM) 467.8 (20.0) ng/ml v 369.3 (22.3) ng/ml, p < 0.01), AGE
      Fl (mean (SEM) 302.2 (13.3) arbitrary units v 204.9 (15.7) arbitrary units, p <
      0.01), and GFR (p < 0.01). CML was positively related to decreased total protein
      and serum albumin and negatively to body mass index (p < 0.01). In contrast, in
      the heart transplant group, impaired GFR was associated with a notable rise of
      both CML (mean (SEM) 876.1 (53.1) ng/ml, p < 0.01) and AGE-Fl (mean (SEM) 385.6
      (26.1) arbitrary units, p < 0.01). A positive relation between CML and serum
      albumin (r = 0.394, p < 0.05) and lipofuscin (r = 0.651, p < 0.01) was found.
      CONCLUSIONS: The contrasting concentration of CML and AGE-Fl between patients
      with CHF and after heart transplantation in the presence of decreased GFR and
      oxidative stress are explained by lowered plasma proteins in CHF and higher
      concentrations in heart transplant recipients. In heart transplant recipients, in
      addition to myocardial inflammatory processes, immunosuppression may be important
      for enhanced formation of AGEs.

PMID- 15486119
TI  - Early detection of cardiac involvement in patients with sarcoidosis by a non
      invasive method with ultrasonic tissue characterisation.
AB  - OBJECTIVES: To clarify the value of cycle dependent variation of myocardial
      integrated backscatter (CV-IB) analysis, which non-invasively measures acoustic
      properties of the myocardium, for early detection of cardiac involvement in
      patients with sarcoidosis. METHODS: The study population consisted of 22
      consecutive patients with biopsy proven sarcoidosis who did not have any abnormal
      findings on conventional two dimensional echocardiogram. Cardiac sarcoidosis was
      diagnosed by radionuclide testing including thallium-201 scintigraphy, gallium-67
      scintigraphy, and cardiac fluorine-18-deoxyglucose positron emission tomography.
      The magnitude and delay of the CV-IB were analysed in the basal mid septum and
      the basal mid posterior wall of the left ventricle of all patients. RESULTS: The
      patients were divided into two groups: 8 patients with cardiac involvement and 14
      patients without cardiac involvement. In the basal septum, a major reduction in
      the magnitude (mean (SD) 1.8 (4.4) v 6.6 (1.3), p = 0.012) and an increase in the
      time delay (1.3 (0.5) v 1.0 (0.1), p = 0.038) of CV-IB were observed in patients
      with cardiac sarcoidosis even in the absence of two dimensional echocardiographic
      abnormalities. The sensitivity for detecting cardiac involvement was such that
      the magnitude of CV-IB in the basal septum discriminated 75% of patients with
      cardiac sarcoidosis from those with non-cardiac sarcoidosis, whereas two
      dimensional echocardiographic parameters did not discriminate between these two
      groups. CONCLUSIONS: The CV-IB is decreased in the basal septum in patients with
      cardiac sarcoidosis even in the absence of two dimensional echocardiographic
      abnormalities. Analysis of CV-IB may be a useful method to detect early
      myocardial involvement in patients with sarcoidosis.

PMID- 15486120
TI  - Braid-like coronary appearance by coronary angiography in systemic lupus
      erythematosis.

PMID- 15486121
TI  - Increased high sensitivity C reactive protein concentrations and increased
      arterial stiffness in children with a history of Kawasaki disease.
AB  - OBJECTIVES: To test the hypothesis that low grade inflammation persists after the
      acute phase and affects arterial stiffness in children with a history of Kawasaki
      disease. DESIGN AND PATIENTS: A cohort of 106 children was studied, which
      comprised 43 patients with Kawasaki disease with coronary aneurysms (group I), 28
      patients with Kawasaki disease with normal coronary arteries (group II), and 35
      healthy age matched children (group III). Their systemic blood pressure, fasting
      cholesterol concentrations, serum high sensitivity C reactive protein (hs-CRP)
      concentrations, and carotid artery stiffness index were compared. Significant
      determinants of serum hs-CRP concentration and carotid artery stiffness were
      identified and the relation between hs-CRP concentration and arterial stiffness
      was investigated. SETTING: Tertiary paediatric cardiac centre. RESULTS: Serum hs
      CRP concentration of group I patients (median 0.39 mg/l, interquartile range 0.28
      0.65 mg/l) was significantly greater than that of group II (median 0.24 mg/l,
      interquartile range 0.17-0.29 mg/l, p < 0.001) and of group III patients (median
      0.25 mg/l, interquartile range 0.18-0.40 mg/l, p < 0.01). Likewise, carotid
      artery stiffness index of group I patients (mean (SD) 5.07 (1.11)) was
      significantly greater than that of group II (4.27 (0.83), p = 0.002), and of
      group III patients (4.24 (0.86), p = 0.001). For the entire cohort, the carotid
      artery stiffness index correlated positively with log serum hs-CRP concentration
      (r = 0.24, p = 0.013). In multiple linear regression analysis, age (standardised
      beta = 0.22, p = 0.02), systolic blood pressure (standardised beta = 0.28, p =
      0.01), log serum hs-CRP concentration (standardised beta = 0.21, p = 0.017), and
      patient grouping (standardised beta = -0.36, p < 0.001) were all independently
      associated with the carotid artery stiffness index. CONCLUSIONS: These findings
      support the possibility of ongoing low grade inflammation late after the acute
      phase of Kawasaki disease in patients with coronary aneurysms. Furthermore, this
      low grade inflammation may have a role in increasing systemic arterial stiffness.

PMID- 15486122
TI  - Homozygous familial hyperlipidaemia presenting as severe aortic stenosis and
      unstable angina.

PMID- 15486123
TI  - Association of increased carotid intima-media thickness with the extent of
      coronary artery disease.
AB  - OBJECTIVE: To investigate (a) the relation between intima-media thickness (IMT)
      in carotid arteries and the extent of coronary artery disease (CAD); and (b)
      whether IMT is predictive of coronary atherosclerosis. The coexistence of severe
      extracranial atherosclerosis in patients with CAD was also analysed. METHODS:
      Coronary angiography and carotid ultrasound evaluation were performed in 558
      consecutive patients (438 men), with a mean (SD) age of 58.8 (9.2) years and
      suspected CAD. Mean IMT was measured at both carotid arteries and expressed as
      the mean aggregate value. The relation between IMT and severity of CAD was
      determined. RESULTS: A significant correlation between mean IMT and advancing CAD
      (p < 0.0001) was found. Four independent predictors of CAD were found in the
      discriminant analysis: age (p = 0.0193), hyperlipidaemia (p < 0.0001), smoking (p
      = 0.0032), and IMT (p < 0.0001). A significant increase in IMT was observed among
      patients with one, two, and three vessel CAD. A log normal distribution of IMT
      values showed that if mean IMT was over 1.15 mm, patients had a 94% probability
      of having CAD, with sensitivity of 65% and specificity of 80% in the patients
      with a high risk of CAD. The number of critically stenosed extracranial arteries
      increased with advancing CAD. None of the patients with normal coronary arteries
      had severe stenosis of the extracranial arteries. Severe carotid, vertebral, or
      subclavian stenosis was found in 16.6% of patients with three vessel CAD.
      CONCLUSIONS: IMT increases with advancing CAD, patients with mean IMT over 1.15
      mm have a 94% likelihood of having CAD, and the coexistence of CAD with severe
      stenosis of aortic arch arteries is relatively high and was found in 16.6% of
      patients with three vessel CAD.

PMID- 15486124
TI  - Coronary blood flow, metabolism, and function in dysfunctional viable myocardium
      before and early after surgical revascularisation.
AB  - OBJECTIVES: To assess the link between perfusion, metabolism, and function in
      viable myocardium before and early after surgical revascularisation. DESIGN:
      Myocardial blood flow (MBF, thermodilution technique), metabolism (lactate,
      glucose, and free fatty acid extraction and fluxes), and function
      (transoesophageal echocardiography) were assessed in patients with critical
      stenosis of the left anterior descending coronary artery (LAD) before and 30
      minutes after surgical revascularisation. SETTING: Tertiary cardiac centre.
      PATIENTS: 23 patients (mean (SEM) age 57 (1.7) years with LAD stenosis: 17 had
      dysfunctional viable myocardium in the LAD territory, as shown by thallium-201
      rest redistribution and dobutamine stress echocardiography (group 1), and six had
      normally contracting myocardium (group 2). RESULTS: LAD MBF was lower in group 1
      than in group 2 (58 (7) v 113 (21) ml/min, p < 0.001) before revascularisation
      and improved postoperatively in group 1 (129 (133) ml/min, p < 0.001) but not in
      group 2 (105 (20) ml/min, p = 0.26). Group 1 also had functional improvement in
      the LAD territory at intraoperative echocardiography (mean regional wall motion
      score from 2.6 (0.85) to 1.5 (0.98), p < 0.01). Oxidative metabolism, with
      lactate and free fatty acid extraction, was found preoperatively and
      postoperatively in both groups; however, lactate and free fatty acid uptake
      increased after revascularisation only in group 1. CONCLUSIONS: MBF is reduced
      and oxidative metabolism is preserved at rest in dysfunctional but viable
      myocardium. Surgical revascularisation yields immediate perfusion and functional
      improvement, and increases the uptake of lactate and free fatty acids.

PMID- 15486125
TI  - Delayed presentation of right ventricular bullet embolus.

PMID- 15486126
TI  - Lack of association between baseline plasma homocysteine concentrations and
      restenosis rates after a first elective percutaneous coronary intervention
      without stenting.
AB  - OBJECTIVE: To evaluate the association between baseline homocysteine
      concentrations and restenosis rates in patients electively undergoing their first
      percutaneous coronary intervention (PCI) without stenting. DESIGN: Prospective,
      single centre, observational study. SETTING AND PATIENTS: Patients electively
      undergoing their first PCI without stenting at a tertiary referral centre between
      1990 and 1998. METHODS: Blood samples were collected from all patients at
      baseline and assayed to determine the patients' homocysteine concentrations.
      Patients whose PCI was successful underwent repeat angiography at a median of 6.4
      (interquartile range 6-6.8) months. Their baseline and follow up angiograms were
      compared by quantitative coronary angiography to assess the incidence of
      restenosis. For the analysis, the patients were divided into two groups based on
      whether their baseline homocysteine concentrations were above or below the median
      value. These two groups were compared to determine whether there was any
      association between their baseline homocysteine concentrations and the incidence
      of restenosis at six months. RESULTS: 134 patients had a successful first PCI
      without stenting (involving 200 lesions). At six month angiography, restenosis
      was observed in 33 patients (49.3%) with baseline homocysteine concentrations
      above the median value and in 31 patients (46.3%) with concentrations below the
      median value (p = 0.74). There was no difference in the percentage of lesions
      developing restenosis (38 (39.6%) v 40 (38.5%), respectively, p = 0.87) or late
      lumen loss (0.40 mm v 0.31 mm, respectively, p = 0.24). On multivariable
      analysis, there was no association between homocysteine concentrations and late
      lumen loss (r = -0.11, p = 0.11) or the percentage diameter stenosis at follow up
      (r = -0.07, p = 0.32). CONCLUSION: Baseline homocysteine concentrations were not
      associated with six month restenosis rates in patients electively undergoing
      their first PCI without stenting.

PMID- 15486128
TI  - Percutaneous sealing of coronary aneurysm by grafted stent implantation.

PMID- 15486127
TI  - Recovery of impaired microvascular function in collateral dependent myocardium
      after recanalisation of a chronic total coronary occlusion.
AB  - OBJECTIVE: To assess the potential for recovery of impaired microvascular
      function in collateral dependent myocardium after recanalisation of a chronic
      total coronary occlusion and the determinants of this recovery. PATIENTS AND
      DESIGN: 120 patients underwent a successful recanalisation of a chronic total
      coronary occlusion (duration > 2 weeks) and a follow up angiography after a mean
      (SD) of 5.0 (1.2) months. The coronary flow velocity reserve (CFVR) and the
      fractional flow reserve were measured after recanalisation and at follow up.
      Global and regional left ventricular (LV) function were analysed by quantitative
      angiography. RESULTS: Microvascular dysfunction, defined by a CFVR < 2.0 and a
      fractional flow reserve > or = 0.75, was observed in 55 (46%) patients after
      recanalisation. Microvascular function improved during follow up in 24 (20%). The
      CFVR increased during follow up from 2.01 (0.58) to 2.50 (0.79) (p < 0.001), due
      to a decrease in basal average peak velocity from 30.7 (14.9) cm/s to 25.5 (13.3)
      cm/s (p = 0.001). Improved microvascular function was associated with an improved
      regional LV function, shown by a correlation between increased wall motion
      severity index and increased CFVR (r = 0.38, p = 0.003). The major determinant of
      microvascular dysfunction at baseline was the presence of diabetes mellitus (odds
      ratio 4.3, 95% confidence interval 1.8 to 10.2), which remained so at follow up
      (odds ratio 4.1, 95% confidence interval 1.3 to 13.4). Improvement of LV function
      was not impaired by the presence of microvascular dysfunction after
      recanalisation. CONCLUSIONS: The frequently observed microvascular dysfunction
      after recanalisation of a chronic total coronary occlusion is a transient
      phenomenon in most patients and is influenced by the presence of diabetes
      mellitus. It does not impede the recovery of LV function. Improved regional LV
      function is associated with improved microvascular function.

PMID- 15486129
TI  - Idiopathic enlargement of the right atrium: 23 year follow up of a familial
      cluster and their unaffected relatives.
AB  - OBJECTIVE: To evaluate the long term outcome of familial idiopathic enlargement
      of the right atrium (IERA) and the risk of developing this disorder among
      unaffected offspring. DESIGN: 23 year follow up study. PATIENTS: 14 members
      (eight men, mean age 54 years, range 40-78) of a pedigree with familial IERA.
      METHODS: All patients were examined clinically and echocardiographically in 1979
      and 2002. Normal cross sectional dimensions of the right atrium were derived from
      echocardiographic evaluation of 100 people (47% men) with no structural or
      haemodynamic signs of heart disease. The 90th centile was chosen as the upper
      normal limit. IERA was defined as an increased right atrial long axis indexed to
      body surface area (RALAX(i), men > 2.6 cm/m2, women > 2.8 cm/m2) in the absence
      of other cardiac abnormalities. Severe IERA was defined arbitrarily as RALAX(i) >
      or = 4 cm/m2. RESULTS: The course of the two index patients with severe IERA
      diagnosed in 1979 was complicated by atrial fibrillation, systemic embolism, and
      symptoms of heart failure without systolic dysfunction, resulting in the death of
      one man (77 years old). One of two patients with initially mild forms progressed
      to severe IERA. All of the initially unaffected offspring (n = 9) remained
      asymptomatic, although four of them had developed mild IERA. CONCLUSIONS: During
      23 years' follow up, severe IERA induced atrial fibrillation, systemic embolism,
      and symptoms of heart failure without systolic dysfunction in all cases in this
      family. Mild IERA seems to become manifest during middle age and may be followed
      by gradual progression to clinically relevant disease.

PMID- 15486130
TI  - A 38 year old well functioning Starr-Edwards valve prosthesis.

PMID- 15486131
TI  - Inheritance of persistent foramen ovale and atrial septal defects and the
      relation to familial migraine with aura.
AB  - OBJECTIVE: To determine whether smaller atrial shunts (large persistent foramen
      ovale (PFO) and small atrial septal defect (ASD)) are inherited and whether this
      has a role in the inheritance of migraine with aura. METHODS: Contrast
      echocardiography was used to detect atrial shunts in 71 relatives of 20 probands
      with a significantly sized atrial shunt (large PFO or ASD). Four families with
      three generations, 14 families with two generations, and two sibships were
      studied. The contrast echocardiograms were performed blind to history of
      migraine. A consultant neurologist, who was blinded to cardiac findings,
      categorised migraine symptoms in subjects. RESULTS: The occurrence of atrial
      shunts was consistent with autosomal dominant inheritance. Usually shunts were
      large PFOs, but in some cases they were ASDs. There was also evidence that
      inheritance of more complex congenital heart disease may be related to the
      inheritance of PFOs. When the proband had migraine with aura and an atrial shunt,
      15 of the 21(71.4%) first degree relatives with a significant right to left shunt
      also had migraine with aura compared with three of 14 (21.4%) without a
      significant shunt (p < 0.02). CONCLUSIONS: There is dominant inheritance of
      atrial shunts. This is linked to inheritance of migraine with aura in some
      families.

PMID- 15486132
TI  - Left ventricular diverticulum in a neonate with Cantrell syndrome.

PMID- 15486133
TI  - Prevalence and development of additional cardiac abnormalities in 1448 patients
      with congenital ventricular septal defects.
AB  - OBJECTIVE: To determine by modern echocardiographic techniques the prevalence and
      development of cardiac abnormalities associated with ventricular septal defect
      (VSD). METHODS: Consecutive patients referred to a tertiary centre for paediatric
      cardiology and attenders at an adult congenital heart disease clinic had details
      of clinical outcome prospectively recorded. Patients with VSD in association with
      conotruncal abnormalities, atrioventricular septal defects, and univentricular
      heart were not included in the study. RESULTS: 1448 patients with VSD were
      assessed between 1991 and 1998. 1127 (78%) patients had isolated defects; of
      these 862 (76%) were perimembranous and 265 (24%) were muscular. Of the
      remainder, 284 (19.6% of the total population) patients had VSD associated with
      one other significant cardiac abnormality: 35 (2.4%) with two and two (0.1%) with
      three other abnormalities. The most common associated cardiac abnormalities were
      infundibular pulmonary stenosis (5.8%), aortic valve prolapse (3.6%), pulmonary
      valvar stenosis (2.7%), osteum secundum atrial septal defect (2.2%), persistent
      ductus arteriosus (1.9%), and coarctation of the aorta (1.5%). In the cohort of
      743 patients followed up from birth, cumulative mortality was 4% by the age of 8
      years and most deaths occurred within the first year of life in infants with
      associated genetic abnormalities such as trisomy 13 or 18. Of the 594 patients
      attending the adult congenital clinic with VSD, aortic regurgitation due to
      aortic root prolapse developed in 45 (7.6%) patients. Most of these cases were
      detected before the patient was 30 years old. CONCLUSIONS: In 22% of patients
      with congenital VSD there were significant associated cardiac abnormalities. Some
      of these abnormalities, such as aortic prolapse and regurgitation or infundibular
      pulmonary stenosis, may develop or progress subsequently and therefore should be
      sought during the initial assessment and monitored during follow up. Follow up to
      the age of 30 years allows the detection of most cases of aortic regurgitation.
      The prognosis from VSD is excellent and the risk of endocarditis in a population
      informed of the need for antibiotic prophylaxis is small.

PMID- 15486134
TI  - Quadri-leaflet pulmonary valve: unusual cause of unexplained murmur.

PMID- 15486135
TI  - Transarterial aortic valve replacement with a self expanding stent in pigs.
AB  - OBJECTIVES: To evaluate the feasibility of percutaneous aortic valve replacement
      without cardiac arrest in animal experiments. METHODS: A self expanding nitinol
      stent, containing pulmonary valves from pigs in its proximal part, was implanted
      in six pigs (94-118 kg) by means of a 25 French catheter through the left
      subclavian artery under guidance of fluoroscopy and transoesophageal
      echocardiography. During stent deployment the original aortic valve was pushed
      against the aortic wall by the self expanding force of the stent while the new
      valve was expanded. RESULTS: It was possible to replace the aortic valve in the
      beating heart in four pigs (67%) with no complication or relevant drop in blood
      pressure. The procedure failed in two pigs (33%) due to dysfunction of the
      catheter device in one case and to problems with correct positioning in the left
      ventricular outflow tract in the other. After successful stent valve
      implantation, dopamine was infused in doses of 5 microg/kg/min, 10 microg/kg/min,
      and 15 microg/kg/min. Cardiac output increased from 4.4 to 8.8 l/min and the mean
      arterial pressure rose from 79 to 105 mm Hg. The maximum peak to peak pressure
      gradient across the valve carrying stent reached a maximum of 8 mm Hg under
      dopamine infusion. All pigs were killed six hours after transvascular aortic
      valve replacement. The chest was opened, and the left ventricle and the ascending
      aorta were carefully inspected. There were no signs of malfunction of the
      implant, of damage of the aortic vessel wall, or of obstruction of the coronary
      ostia. CONCLUSIONS: Percutaneous aortic valve replacement with a self expanding
      nitinol stent in the beating heart is possible. The device was safe under
      pharmacological stress test. After successful chronic animal experiments, this
      concept may become a feasible option for treating patients with relevant aortic
      valve disease but where open heart surgery would be risky.

PMID- 15486136
TI  - Acute massive pulmonary thromboembolism simulating anterolateral myocardial
      ischaemia.

PMID- 15486137
TI  - Secondary prevention of coronary heart disease in South Wales: a survey following
      myocardial infarction.

PMID- 15486138
TI  - Reduction in plasma concentrations of N terminal pro B type natriuretic peptide
      following percutaneous coronary intervention.

PMID- 15486139
TI  - Association of the ile405val mutation in cholesteryl ester transfer protein gene
      with risk of acute myocardial infarction.

PMID- 15486140
TI  - Echocardiography in differentiating tuberculous from chronic idiopathic
      pericardial effusion.

PMID- 15486141
TI  - Radial approach to day case intervention in coronary artery lesions (RADICAL): a
      single centre safety and feasibility study.

PMID- 15486142
TI  - Incidence and factors influencing left atrial clot in patients with mitral
      stenosis and normal sinus rhythm.

PMID- 15486143
TI  - A trial of early discharge with homecare compared to conventional hospital care
      for patients undergoing coronary artery bypass grafting.

PMID- 15486144
TI  - Thrombolytic treatment in diabetic patients with acute myocardial infarction:
      lower rates of use than in non-diabetic patients are explained by differences in
      presenting ECGs.

PMID- 15486145
TI  - Aortic coarctation: prognostic indicators of survival in the fetus.

PMID- 15486146
TI  - Direct demonstration of coronary collateral growth by physical endurance exercise
      in a healthy marathon runner.

PMID- 15486147
TI  - Should all patients with an acute myocardial infarction be referred for direct
      PTCA?

PMID- 15486148
TI  - Should patients with acute ST elevation MI be transferred for primary PCI?

PMID- 15486149
TI  - Relapsing pericarditis.

PMID- 15486150
TI  - Where is the evidence for holistic nursing care?

PMID- 15486151
TI  - Developing holistic nursing interventions to improve adolescent health.
AB  - Adolescents learn health behaviors in a sociocultural context of community,
      family, and peers. Although many adolescents engage in behaviors that protect and
      promote health, others engage in behaviors that threaten or compromise their
      health. The purpose of this review article is to provide an overview of health
      risk behaviors and the morbidities and mortalities of adolescence that are
      related to these behaviors. Interventions that address these health behaviors and
      outcomes are presented along with suggestions for a holistic nursing response to
      this important public health concern.

PMID- 15486152
TI  - Efficacy of therapeutic touch in treating pregnant inpatients who have a chemical
      dependency.
AB  - Chemical dependency is known to complicate about 3.8% of pregnancies in
      Vancouver, British Columbia, Canada. In this study, 54 English-speaking,
      hospitalized women were randomly assigned to receive either (a) daily Therapeutic
      Touch over a 7-day period for 20 minutes each day, (b) shared activity with a
      registered nurse for 20 minutes over a 7-day period, or (c) standard ward care.
      Anxiety was measured using Spielberger's State-Trait Anxiety Inventory.
      Withdrawal symptoms were measured using a standardized Symptom Checklist. Anxiety
      scores were significantly less on Days 1, 2, and 3 (p<.05) for the group
      receiving Therapeutic Touch. Therapeutic Touch may be of value as an adjunctive
      measure in the treatment of chemical dependency among pregnant women.

PMID- 15486153
TI  - Striving for purity: shared understandings in retired Swedish care providers'
      narratives on nursing care around 1950.
AB  - Caring for the sick has been important throughout all times. Nursing care has
      been illuminated from various perspectives. The aim of this study was to
      illuminate nursing care as narrated by 27 retired care providers in northern
      Sweden. The themes of cleanliness, order, and clear conscience stood out as
      important in the text. The results are interpreted as pointing to purity. Purity
      is a complex phenomenon within the cultural context. Some literature states that
      in the past, physical cleanliness, moral purity, and order were closely
      interrelated. Nurses were expected to be religious, morally pure persons in clean
      and perfect uniforms, always prepared to serve and do their duty. Purity is not
      always readily apparent. It is often revealed through its absence or opposite.
      Purity and conscience are seldom addressed in contemporary nursing research. More
      research is needed to further reflect on purity and its significance for nursing
      care today.

PMID- 15486154
TI  - Qigong as a therapeutic intervention with older adults.
AB  - The use of complementary therapies in the United States is growing. One
      complementary therapy that has received little attention in the nursing
      literature is Qigong. Qigong is the cornerstone of traditional Chinese medicine
      and consists of gentle flowing body movements, breathing, and quieting the mind.
      Qigong facilitates the movement of qi, the vital life energy, throughout the
      body, thereby enhancing health and healing disease. Preliminary research
      indicates that Qigong may be an effective complementary therapy for promoting
      health and wellness in older adults and an effective adjuvant intervention for
      managing chronic conditions in older adults. This article provides an overview of
      Qigong, reviews the English-language research literature on the therapeutic
      effects of Qigong, discusses the implications of Qigong as a complementary
      therapy for older adults, and suggests directions for further research on the use
      of Qigong as a therapeutic approach for older adults.

PMID- 15486155
TI  - A place for aesthetics: aesthetics' place is in life--and in nursing!
AB  - This article explores the relationship between aesthetics and the activities of
      daily life for nurses and for other human beings. The author relates a personal
      experience and describes some definitions and history surrounding our need for
      beauty.

PMID- 15486156
TI  - A narrative study of nursing art in critical care.
AB  - The purpose of this study was to describe nursing art from the perspective of
      patients who had been nursed in a critical care unit. The study pursued two
      objectives: (a) to generate stories of occasions in which nursing was considered
      art in a critical care setting and (b) to describe the meanings made manifest in
      those stories. Using a narrative inquiry, 10 persons were interviewed twice for
      the purpose of answering the research question. Stories were generated in open
      ended interviews, tape recorded, and analyzed by the primary researcher using Van
      Manen's hermeneutic phenomenological framework. Five themes were found to
      represent critically ill persons' experience of nursing art: (a) perpetual
      presence, (b) knowing the other, (c) intimacy and agony, (d) deep detail, and (e)
      honoring the body. The stories cultivated a human face and contextual detail for
      the abstract holistic concept of nursing art.

PMID- 15486158
TI  - Funding collaborative juvenile crime prevention programs: does it make a
      difference?
AB  - Panel data were analyzed to determine whether funding for collaborative juvenile
      crime prevention programs reduced arrests in California counties. Because the
      data were a population (i.e., all 58 counties in the state), regression results
      were summarized descriptively, and special attention was given to the direction
      and magnitude of key coefficients. Funding was associated with little to no
      overall reductions in arrests for felonies, misdemeanors, and status offenses.
      However, estimates of arrests prevented varied across each of the 14 counties
      that received funding.

PMID- 15486159
TI  - Measuring the impacts of community development initiatives: a new application of
      the adjusted interrupted time-series method.
AB  - The authors contribute to the development of empirical methods for measuring the
      impacts of place-based local development strategies by introducing the adjusted
      interrupted time-series (AITS) approach. It estimates a more precise
      counterfactual scenario, thus offering a stronger basis for drawing causal
      inferences about impacts. The authors applied the AITS approach to three
      community development initiatives using single-family home prices as the outcome
      indicator and found that it could measure impacts on both the base level of
      prices and the rate of price appreciation. The authors also found a situation in
      which the method appears unreliable, however. The AITS approach benefits from
      more recurrent data on outcomes during the pre-and post-intervention periods,
      with an intertemporal pattern that avoids great volatility. The AITS approach to
      measuring effects of community development initiatives holds strong promise, with
      caveats.

PMID- 15486160
TI  - The Doubles: a case study on developing a technology-based substance abuse
      education curriculum.
AB  - The Doubles, funded by the National Institute on Drug Abuse, is a seven-episode
      series of media tools designed to teach third and fourth grade students about the
      science of drug addiction. The program's curriculum is delivered via a set of
      videos, interactive CD-ROMs, workbooks, or an Internet site. This article
      examines the process used to develop The Doubles and argues that its success
      stems from the careful balancing of the needs of the funding agency, state and
      national curricular guidelines, and the target audience.

PMID- 15486161
TI  - Passive versus active parental permission in school-based survey research: does
      the type of permission affect prevalence estimates of risk behaviors?
AB  - This study investigates whether the type of parental permission affects
      prevalence estimates for risk behaviors from the national 2001 Youth Risk
      Behavior Survey. Participants were 13,195 students from 143 schools, of which 65%
      used passive permission and 35% active permission. Student participation rates
      were 86.7% in passive permission schools and 77.3% in active permission schools.
      For 24 of 26 behaviors tested, no significant differences were seen in the
      prevalence of risk behavior by type of parental permission. As long as high
      response rates are obtained, type of parental permission does not affect
      prevalence estimates for risk behaviors that are based on self-report.

PMID- 15486162
TI  - Factors influencing middle and high schools' active parental consent return
      rates.
AB  - The authors examined factors influencing the return rates for attempting to
      collect active parental consent forms from 21,123 students in the 7th through
      10th grades in 41 middle and high schools. Overall return rates from middle
      schools were higher than from high schools. Schools that offered high levels of
      staff support for collecting consent forms had higher return rates. Procedures
      where the consent form was attached to a school form that parents had to complete
      and return to the school yielded the highest return rate. Implications for how
      researchers can obtain a high parent consent form return rate are discussed.

PMID- 15486164
TI  - Predictors of neuropsychological test performance after pediatric traumatic brain
      injury.
AB  - The influence of neurological and demographic variables on neuropsychological
      test performance was examined in 100 9-to 16-year-old children with traumatic
      brain injury (TBI). Regression analyses were conducted to determine the relative
      contributions of coma, neuroimaging findings, ethnicity, socioeconomic status,
      and gender to variance in performance on the Wechsler Intelligence Scale for
      Children-Third Edition (WISC-III), California Verbal Learning Test--Children's
      Version (CVLT-C), and the Children's Category Test. Both neurological and
      demographic variables contributed to performance on various WISC-III factor index
      scores as well as the CVLT-C. No evidence for a moderating effect of demographic
      variables was found, but speed of information processing mediated the effect of
      neurological and demographic variables on CLVT-C performance. It is concluded
      that demographic variables have an incremental effect on the neuropsychological
      test performance of children with TBI above and beyond the influence of injury
      severity.

PMID- 15486165
TI  - Test-retest reliability and standard error of measurement for the test of
      variables of attention (T.O.V.A.) with healthy school-age children.
AB  - Test-retest reliability of the Test of Variables of Attention (T.O.V.A.) was
      investigated in two studies using two different time intervals: 90 min and 1 week
      (2 days). To investigate the 90-min reliability, 31 school-age children (M = 10
      years, SD = 2.66) were administered the T.O.V.A. then read ministered the test 90
      min afterward. Significant reliability coefficients were obtained across omission
      (.70), commission (.78), response time (.84), and response time variability
      (.87). For the second study, a different sample of 33 school-age children (M =
      10.01 years, SD = 2.59) were administered the test then read ministered the test
      1 week later. Significant reliability coefficients were obtained for omission
      (.86), commission (.74), response time (.79), and response time variability
      (.87). Standard error of measurement statistics were calculated using the
      obtained coefficients. Commission scores were significantly higher on second
      trials for each retest interval.

PMID- 15486166
TI  - An examination and replication of the psychometric properties of the
      Massachusetts Youth Screening Instrument--second edition (MAYSI-2) among
      adolescents in detention settings.
AB  - There is a high prevalence of psychological disorders among adolescents in
      detention facilities. The need for a simple, effective screening tool led to the
      development of the Massachusetts Youth Screening Instrument (MAYSI) and its
      successor, the MAYSI-2. This study evaluated the MAYSI-2 psychometric properties
      based on the records of 704 youths evaluated at intake to detention facilities.
      In addition to factor structure, the study evaluated test-retest reliability and
      concurrent external validity. Results were generally encouraging in terms of the
      use of MAYSI-2 in detention facilities, and directions for future research are
      discussed.

PMID- 15486167
TI  - Adolescent personality: a five-factor model construct validation.
AB  - The purpose of this study was to investigate convergent and discriminant validity
      of the five-factor model of adolescent personality in a school setting using
      three different raters (methods): self-ratings, peer ratings, and teacher
      ratings. The authors investigated validity through a multitrait-multimethod
      matrix and a confirmatory factor analysis correlated trait, uncorrelated method
      model. With the exception of Emotional Stability, each analysis demonstrated
      similar patterns and together provided support for the convergent and
      discriminant validity of the five-factor model structure of adolescent
      personality. However, among the three raters, self-ratings of personality
      provided a comparatively weaker method for assessing adolescent personality. The
      influences of agreement between self and other raters are discussed in relation
      to contrast, perceiver, and target effects; expert observer effects; the degree
      of acquaintanceship; and the effect of the social context.

PMID- 15486168
TI  - Relative user ratings of MMPI-2 computer-based test interpretations.
AB  - There are eight commercially available computer-based test interpretations
      (CBTIs) for the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), of which
      few have been empirically evaluated. Prospective users of these programs have
      little scientific data to guide choice of a program. This study compared ratings
      of these eight CBTIs. Test users were randomly assigned to rate either a single
      authentic CBTI report on one of their clients or a single CBTI report generated
      from a modal MMPI-2 profile for their clinical setting. In all, 257 authentic and
      modal CBTI reports were rated by 41 clinicians on 10 dimensions. Each of the
      authentic reports received substantially higher ratings than the modal reports,
      with ratings of perceived accuracy and opinion confirmation best differentiating
      between authentic and modal reports. Automated Assessment Associates' report
      received the highest overall ratings; reports published by Western Psychological
      Services, Pearson Assessments, and the Caldwell Report were also distinguished on
      one or more ratings dimensions.

PMID- 15486169
TI  - Psychometric properties of the life events checklist.
AB  - The Life Events Checklist (LEC), a measure of exposure to potentially traumatic
      events, was developed at the National Center for Posttraumatic Stress Disorder
      (PTSD) concurrently with the Clinician Administered PTSD Scale (CAPS) to
      facilitate the diagnosis of PTSD. Although the CAPS is recognized as the gold
      standard in PTSD symptom assessment, the psychometric soundness of the LEC has
      never been formally evaluated. The studies reported here describe the performance
      of the LEC in two samples: college undergraduates and combat veterans. The LEC
      exhibited adequate temporal stability, good convergence with an established
      measure of trauma history -- the Traumatic Life Events Questionnaire (TLEQ) --
      and was comparable to the TLEQ in associations with variables known to be
      correlated with traumatic exposure in a sample of undergraduates. In a clinical
      sample of combat veterans, the LEC was significantly correlated, in the predicted
      directions, with measures of psychological distress and was strongly associated
      with PTSD symptoms.

PMID- 15486170
TI  - The Salient Stressor Impact Questionnaire (SSIQ): a measurement of the intensity
      and chronicity of stress.
AB  - High stress is known to affect health, but stress impact, determined by events
      and responses to them, has not been studied systematically. For the Salient
      Stressor Impact Questionnaire (SSIQ), the impact of events was assumed to depend
      on their salience and chronicity and the impact of responses on their chronicity
      and intensity with greater unfavorable appraisal associated with greater
      response. The SSIQ assessed a person's two most salient stressors. Chronicity
      items discriminated between clinically stressed and nonclinical participants and
      measured the chronicity of stressful feelings (distress) and the event. The
      remaining items measured the degree of distress and unfavorable appraisal. The
      SSIQ showed good test-retest and internal consistency reliability, concurrent
      validity, and stability across diverse populations. Exploratory analyses grouped
      items into distress, chronicity, and appraisal elements, and confirmatory
      analysis revealed a good fit to the hypothesized model. Preliminary data suggest
      that the SSIQ will be useful for studying relationships between stress and
      health.

PMID- 15486171
TI  - Factor structure of the Penn State Worry Questionnaire: examination of a method
      factor.
AB  - The Penn State Worry Questionnaire (PSWQ) was originally designed as a
      unifactorial measure of pathological trait worry. However, recent studies
      supported a two-factor solution with positively worded items loading on the first
      factor and reverse-scored items loading on a second factor. The current study
      compared this two-factor model to a negative wording method factor solution among
      college students. A method factor model with all PSWQ items loading on a single
      worry factor and reverse-scored items loading on a negative wording method factor
      provided as good a fit as the two-factor model. This method factor alone did not
      predict a generalized anxiety disorder diagnosis. Finally, the psychometric
      properties of an abbreviated scale containing only positively worded items were
      examined. The PSWQ appears to measure a single unitary construct, but response
      patterns differ between positively worded and reverse-scored items. Theoretical
      implications for pathological worry and assessment-related issues are discussed.

PMID- 15486173
TI  - Training in occupational medicine: are we as good as we think we are?

PMID- 15486174
TI  - Occupational dermatoses: overview.

PMID- 15486175
TI  - Occupational skin infections.
AB  - A number of skin infections may complicate different occupations depending on the
      working environment and level of exposure to a particular agent. These in turn
      may affect the productivity of an individual worker and ultimately the company as
      a whole. This review aims to highlight some common and important skin infections
      that may be acquired at work. Epidemiology, clinical features, diagnosis,
      treatment and prevention will be covered.

PMID- 15486176
TI  - Strategies for prevention: occupational contact dermatitis.
AB  - The economic consequence of occupational contact dermatitis (OCD) is considerable
      and impacts on an individual's quality of life. There are a range of prevention
      strategies, which include: elimination or substitution of harmful exposures;
      technical control measures; personal protection; identification of susceptible
      individuals; and education, training and health surveillance. Each one has been
      shown to have varying degrees of success in reducing OCD, but further work is
      required to evaluate the effectiveness of preventive measures in the workplace.
      OCD is not considered a high priority in most affected industries and therefore
      the development of health and safety policies to reduce its prevalence should be
      encouraged, although guidance and assistance would be required, because all
      employees are entitled to a safe working environment.

PMID- 15486177
TI  - Occupational skin cancers.
AB  - Skin cancer due to occupation is more common than is generally recognized,
      although it is difficult to obtain an accurate estimate of its prevalence. Over
      the past two centuries, occupational skin cancers have particularly been due to
      industrial exposure of men (it seems more so than women) to chemical carcinogens
      such as polycyclic hydrocarbons (e.g. from coal tar products) or to arsenic.
      Industrial processes have improved in most Western countries to limit this type
      of exposure, but those with outdoor occupations are still exposed to solar
      ultraviolet irradiation without this being widely recognized as an industrial
      hazard. Ionizing radiation such as X-rays can also cause skin cancer.
      Occupational skin cancers often resemble skin tumours found in non-occupational
      subjects, e.g. basal cell carcinoma, squamous cell carcinoma and malignant
      melanoma, but some pre-malignant lesions can be more specific and point to an
      occupational origin, e.g. tar keratoses or arsenical keratoses. An uncommon but
      well-recognized cause of occupational skin cancer is that which results from scar
      formation following an industrial burn. In the future it will be necessary to
      focus on preventative measures, e.g. for outdoor workers, the need to cover up in
      the sun and use sun protective creams and a campaign for earlier recognition of
      skin cancers, which are usually curable if treated in their early stages.

PMID- 15486178
TI  - Report of a system for diagnosis, categorizing and recording occupational mental
      ill-health.
AB  - BACKGROUND: UK statutory systems for occupational disease recording do not
      include mental illness resulting from occupational stress. The issue is included
      within physician reporting systems, but there is no agreed set of criteria for
      diagnosis of occupational causation and no agreed system of categorization in
      terms of type of causation by workplace factors. METHOD: A multidisciplinary
      group of occupational health professionals, in conjunction with human resources
      staff, developed a system for the diagnosis, categorization and recording of
      occupational mental ill-health. RESULTS: The developed system was applied as a
      pilot and the outcome from its first year of use is presented. CONCLUSIONS: The
      system is considered to have operated well in pilot, and has now been adopted as
      a standard operating procedure by the occupational health provider who developed
      it. The system is proposed as a tool in the development of standardized NHS or UK
      national systems for the recording of occupational mental ill-health.

PMID- 15486180
TI  - Respiratory and cardiovascular function at rest and during exercise testing in a
      healthy working population: effects of outdoor traffic air pollution.
AB  - BACKGROUND: There is controversy regarding long-term adverse effects of urban
      pollutants in urban workers. AIM: The aim of this study was to evaluate the
      effects of urban pollutants on respiratory and cardiovascular function in exposed
      traffic policemen compared to a control group. METHODS: Sixty-eight traffic
      policemen and 62 controls (all male) were investigated at rest and during symptom
      limited incremental exercise test (performed with a cycle ergometer). The data
      were statistically evaluated. RESULTS: There were no significant differences in
      the mean values of resting ventilatory capacity, the forced spirometric test, or
      in blood gas parameters between the groups. The traffic exposed group
      demonstrated a number of significant changes in cardiorespiratory measures on
      exercise testing. Twenty-six traffic policemen and none of the controls
      experienced exercise-induced ECG abnormalities, hypertension or oxyhaemoglobin
      desaturation; 80% of the 26 had resting PaO(2) values <80 mmHg. CONCLUSION: The
      findings suggest that chronic occupational exposure to urban pollutants reduces
      resistance to physical effort and increases the risk of cardiovascular and
      respiratory changes including slight hypoxemia.

PMID- 15486179
TI  - Olfactory loss in poly (acrylonitrile-butadiene-styrene) plastic injection
      moulding workers.
AB  - BACKGROUND: Plastics manufacturing factories are the fifth largest category of
      factories in industrial estates in Taiwan. It is known that complex airborne
      compounds and pungent odours are emitted during plastic injection-moulding
      processes. Workers exposed to acrylonitrile-butadiene-styrene (ABS) thermal
      decomposition products (TDP) may have olfactory loss. AIMS: This study examined
      olfactory loss in injection-moulding workers exposed to ABS TDP. METHODS: The
      method recommended by the Connecticut Chemosensory Clinical Research Center
      (CCCRC) was used to test the olfactory function of subjects, including 1-butanol
      threshold and odour identification, both pre- and post-work. The study sample
      included 52 ABS plastic injection-moulding workers (exposed group), as well as 72
      workers from other departments (reference group). RESULTS: The results revealed
      that the exposed group had lower olfactory function after work than the reference
      group. The decrease in olfactory function after 1 workday was statistically
      significant. The prevalence of abnormal olfactory function post-work in the
      exposed group was higher than in the reference group. CONCLUSIONS: The findings
      of this study implied the ABS plastic injection-moulding process may worsen
      olfactory function among workers. Notably, this effect decreased olfactory
      threshold scores, not odour identification scores.

PMID- 15486181
TI  - The history of woolsorters' disease: a Yorkshire beginning with an international
      future?
AB  - Woolsorters' disease was a feared industrial disease associated primarily with
      Yorkshire's textile industry of the nineteenth and early twentieth centuries.
      Early occupational health methods were attempted locally before concerted
      national efforts produced legislative measures. When its link with anthrax was
      established, attention in prevention focused upon chemical disinfection methods.
      Together, these factors were instrumental in decreasing the incidence of
      woolsorters' disease. However, by the beginning of the Second World War, the lack
      of treatment options for anthrax meant that the bacterium was experimented upon
      as a potential war-winning weapon. Today, woolsorters' disease and other
      industrial manifestations of anthrax are extremely rare, but the increasing
      threat of bioterrorism means that the international dread and historical lessons
      of this significant condition should never be forgotten. Consequently, this paper
      reveals the history of woolsorters' disease in order to remind those involved in
      occupational medicine today of the dread it caused both physicians and workers in
      previous generations.

PMID- 15486182
TI  - Rounded atelectasis in an asbestos exposed worker.
AB  - The case history is presented of a 51-year-old electrical power worker with a
      history of asbestos exposure presenting with rounded atelectasis. No other
      radiological markers of asbestos exposure were present. A documented history of
      asbestos exposure and exclusion of other causes of rounded atelectasis led to the
      diagnosis of asbestos related rounded atelectasis. It is important to understand
      that rounded atelectasis can be an isolated finding due to asbestos exposure.
      This facilitates investigation of lung masses of unknown etiology and initiation
      of appropriate follow up of patients at risk for future development of more
      debilitating asbestos related pathology.

PMID- 15486183
TI  - A possible case of pneumoconiosis in a limestone quarry worker.
AB  - BACKGROUND: A 43-year-old man presented with wheeze and shortness of breath. He
      had an occupational history of working in a limestone quarry. Pulmonary function
      testing revealed a mixed obstructive/restrictive defect. Chest X-ray revealed
      nodular shadowing throughout both lung fields. METHODS: Subsequent thoracoscopic
      lung biopsy was performed and histology of the nodules revealed a foreign body
      granulomatous reaction with numerous fluorescent particles seen under polarized
      light. There was no evidence of interstitial fibrosis. RESULTS: Energy dispersive
      X-ray analysis (EDXA) scanning confirmed that these particles contained calcium,
      aluminium and silicon and had a composition consistent with limestone.
      CONCLUSIONS: This case demonstrates a possible unusual reaction to inorganic dust
      particles without resultant fibrosis.

PMID- 15486184
TI  - Novel single-stranded oligonucleotides that inhibit signal transducer and
      activator of transcription 3 induce apoptosis in vitro and in vivo in prostate
      cancer cell lines.
AB  - Signal transducers and activators of transcription (STAT) were originally
      discovered as components of cytokine signal transduction pathways. Persistent
      activation of one of these transcription factors, STAT3, is a feature of many
      malignancies, including hormone-resistant prostate cancer. In this regard,
      malignant cells expressing persistently activated STAT3 become dependent on it
      for survival, thus rendering STAT3 a potential molecular target for therapy of
      hormone-resistant prostate cancer. Previously, we reported that antisense
      oligonucleotides specific for STAT3 were better at inducing apoptosis than
      inhibitors of JAK1 or JAK2, the upstream activating kinases of STAT3. Here, we
      report that novel single-stranded oligonucleotides, which putatively block STAT3
      DNA binding, were better at inducing hormone-resistant prostate cancer apoptosis
      than antisense STAT3 oligonucleotides. We observed that the novel STAT3
      inhibiting oligonucleotides induced apoptosis by a mitochondrial-dependent
      pathway involving the activation of caspase-3. Prostate cell lines not expressing
      persistently activated STAT3 did not become apoptotic after treatment with these
      same oligonucleotides. Scrambled-sequence control oligonucleotides had none of
      the effects of the active sequence oligonucleotides on any variable measured.
      Furthermore, the novel STAT3-inhibiting oligonucleotides, but not scrambled
      sequence control oligonucleotide, significantly reduced the volume of s.c. DU145
      tumors in vivo. Histologic examination of the tumors revealed no infiltrate of
      mononuclear or granulocytic cells, which would be indicative of evocation of a
      nonspecific immune response by the oligonucleotides. We conclude that single
      stranded oligonucleotides based on the binding sequences of STAT3 are an
      additional strategy to design inhibitors for this molecular target and that these
      inhibitors should be useful as experimental therapeutics for hormone-resistant
      prostate cancer.

PMID- 15486185
TI  - Targeting heterogeneous nuclear ribonucleoparticule A1 and A2 proteins by RNA
      interference promotes cell death in transformed but not in normal mouse cell
      lines.
AB  - The heterogeneous nuclear ribonucleoparticule A1 and A2 proteins can bind to
      vertebrate single-stranded telomeric sequences. Moreover, changes in the levels
      of heterogeneous nuclear ribonucleoparticule A1 can influence telomere length in
      mouse and human cells. We have shown previously that the combined knockdown of A1
      and A2 proteins in human transformed cells promotes apoptosis. In contrast, a
      similar reduction in A1 and A2 expression in normal mortal human cell lines does
      not induce cell death. Here, we show that a variety of mouse cell lines display a
      similar behavior on reduction of A1 and A2 protein levels using small interfering
      RNA. In addition, the expression of the mouse A1 cDNA protects human HeLa cells
      from apoptosis when human A1 and A2 proteins are targeted by RNA interference.
      Lastly, we show that knockdown of A1 and A2 expression also impairs the growth of
      a human transformed cell line that does not express telomerase. These results
      firmly establish A1 and A2 as proteins required for the viability of transformed
      murine and human cells, irrespective of the status of telomerase expression or
      the length of the double-stranded telomeric repeat.

PMID- 15486186
TI  - A G-quadruplex telomere targeting agent produces p16-associated senescence and
      chromosomal fusions in human prostate cancer cells.
AB  - The trisubstituted acridine derivative BRACO-19 has been designed to interact
      with and stabilize the quadruplex DNA structures that can be formed by folding of
      the single-stranded repeats at the 3' end of human telomeres. We suggest that the
      BRACO-19 complex inhibits the catalytic function of telomerase in human cancer
      cells and also destabilizes the telomerase-telomere capping complex so that cells
      enter senescence. Here, we present evidence showing that the inhibition of cell
      growth caused by BRACO-19 in DU145 prostate cancer cells occurs more rapidly than
      would be expected solely by the inhibition of the catalytic function of
      telomerase, and that senescence is accompanied by an initial up-regulation of the
      cyclin-dependent kinase inhibitor p21, with subsequent increases in p16(INK4a)
      expression. We also show that treatment with BRACO-19 causes extensive end-to-end
      chromosomal fusions, consistent with telomere uncapping.

PMID- 15486187
TI  - Topoisomerase-II alpha expression as a predictive marker in a population of
      advanced breast cancer patients randomly treated either with single-agent
      doxorubicin or single-agent docetaxel.
AB  - PURPOSE: The predictive value of topoisomerase-II alpha (topo-II) has been
      evaluated in advanced breast cancer patients randomly treated with single-agent
      doxorubicin or docetaxel. EXPERIMENTAL DESIGN: Primary tumor samples from
      patients enrolled in a randomized, phase III clinical trial comparing single
      agent doxorubicin (75 mg/m(2) q3wks) with docetaxel (100 mg/m(2) q3wks) were
      collected and topo-II status was evaluated by immunohistochemistry (clone KiS1).
      RESULTS: Topo-II status was evaluated in 108 samples, 55 (51%) in the doxorubicin
      arm and 53 (49%) in the docetaxel arm. An increment of 10% in cells expressing
      topo-II is associated with a statistically significant odds ratio (OR; 95%
      confidence interval) of 1.09 (1.03-1.15; P = 0.002) for overall response to
      doxorubicin versus 1.002 (0.94-1.07; P = 0.95) in the docetaxel arm. With
      increasing topo-II, the favorable OR for overall response to docetaxel compared
      with doxorubicin decreases to become not significant in patients with topo-II
      tumor content >10%. In a multivariate analysis, (a) HER-2 status seems positively
      correlated with overall response to chemotherapy (OR, 2.34; 95% confidence
      interval, 0.87-6.27; P = 0.09). (b) Overall response to doxorubicin is
      significantly lower than overall response to docetaxel (OR, 0.17; 95% confidence
      interval, 0.04-0.64; P = 0.009) but with a significant interaction term for
      doxorubicin-treated patients with topo-II tumor content >10% (OR, 8.31; 95%
      confidence interval, 1.86-37.03; P = 0.05). CONCLUSIONS: (a) Topo-II
      overexpression confers a higher probability of response in the doxorubicin arm
      only. (b) Despite being a small retrospective study, this study is in line with
      previously reported studies and the hypotheses raised are now being tested in a
      prospective neoadjuvant trial.

PMID- 15486188
TI  - Sensitization of a human ovarian cancer cell line to temozolomide by simultaneous
      attenuation of the Bcl-2 antiapoptotic protein and DNA repair by O6-alkylguanine
      DNA alkyltransferase.
AB  - Temozolomide is an alkylating agent that mediates its cytotoxic effects via O(6)
      methylguanine (O(6)-meG) adducts in DNA. O(6)-alkylguanine-DNA-alkyltransferase
      (MGMT) can repair such adducts and therefore constitutes a major resistance
      mechanism to the drug. MGMT activity can be attenuated in vitro and in vivo by
      the pseudosubstrate O(6)-(4-bromothenyl)guanine (PaTrin-2, Patrin, Lomeguatrib),
      which in clinical trials is in combination with temozolomide. Resistance to
      cytotoxic agents can also be mediated by the Bcl-2 protein, which inhibits
      apoptosis and is frequently up-regulated in tumor cells. Attenuation of Bcl-2
      expression can be affected by treatment of cells with the antisense
      oligonucleotide, oblimersen sodium (Genasense), currently in phase III clinical
      trials in combination with the methylating agent dacarbazine. Using a human
      ovarian cancer cell line (A2780) that expresses both Bcl-2 and MGMT, we show that
      cells treated with active dose levels of either oblimersen (but not control
      reverse sequence or mismatch oligonucleotides) or PaTrin-2 are substantially
      sensitized to temozolomide. Furthermore, the exposure of oblimersen-pretreated
      cells to PaTrin-2 leads to an even greater sensitization of these cells to
      temozolomide. Thus, growth of cells treated only with temozolomide (5 microg/mL)
      was 91% of control growth, whereas additional exposure to PaTrin-2 alone (10
      micromol/L) or oblimersen alone (33 nmol/L) reduced this to 81% and 66%,
      respectively, and the combination of PaTrin-2 (10 micromol/L) and oblimersen (33
      nmol/L) reduced growth to 25% of control. These results suggest that targeting
      both Bcl-2 with oblimersen and MGMT with PaTrin-2 would markedly enhance the
      antitumor activity of temozolomide and merits testing in clinical trials.

PMID- 15486189
TI  - Inhibition of Chk1 by the G2 DNA damage checkpoint inhibitor isogranulatimide.
AB  - Inhibitors of the G(2) DNA damage checkpoint can selectively sensitize cancer
      cells with mutated p53 to killing by DNA-damaging agents. Isogranulatimide is a
      G(2) checkpoint inhibitor containing a unique indole/maleimide/imidazole skeleton
      identified in a phenotypic cell-based screen; however, the mechanism of action of
      isogranulatimide is unknown. Using natural and synthetic isogranulatimide
      analogues, we show that the imide nitrogen and a basic nitrogen at position 14 or
      15 in the imidazole ring are important for checkpoint inhibition.
      Isogranulatimide shows structural resemblance to the aglycon of UCN-01, a potent
      bisindolemaleimide inhibitor of protein kinase C beta (IC(50), 0.001 micromol/L)
      and of the checkpoint kinase Chk1 (IC(50), 0.007 micromol/L). In vitro kinase
      assays show that isogranulatimide inhibits Chk1 (IC(50), 0.1 micromol/L) but not
      protein kinase C beta. Of 13 additional protein kinases tested, isogranulatimide
      significantly inhibits only glycogen synthase kinase-3beta (IC(50), 0.5
      micromol/L). We determined the crystal structure of the Chk1 catalytic domain
      complexed with isogranulatimide. Like UCN-01, isogranulatimide binds in the ATP
      binding pocket of Chk1 and hydrogen bonds with the backbone carbonyl oxygen of
      Glu(85) and the amide nitrogen of Cys(87). Unlike UCN-01, the basic N15 of
      isogranulatimide interacts with Glu(17), causing a conformation change in the
      kinase glycine-rich loop that may contribute importantly to inhibition. The
      mechanism by which isogranulatimide inhibits Chk1 and its favorable kinase
      selectivity profile make it a promising candidate for modulating checkpoint
      responses in tumors for therapeutic benefit.

PMID- 15486190
TI  - G2 cell cycle arrest, down-regulation of cyclin B, and induction of mitotic
      catastrophe by the flavoprotein inhibitor diphenyleneiodonium.
AB  - Because proliferation of eukaryotic cells requires cell cycle-regulated chromatid
      separation by the mitotic spindle, it is subject to regulation by mitotic
      checkpoints. To determine the mechanism of the antiproliferative activity of the
      flavoprotein-specific inhibitor diphenyleneiodonium (DPI), I have examined its
      effect on the cell cycle and mitosis. Similar to paclitaxel, exposure to DPI
      causes an accumulation of cells with a 4N DNA content. However, unlike the
      paclitaxel-mediated mitotic block, DPI-treated cells are arrested in the cell
      cycle prior to mitosis. Although DPI-treated cells can arrest with fully
      separated centrosomes at opposite sides of the nucleus, these centrosomes fail to
      assemble mitotic spindle microtubules and they do not accumulate the Thr(288)
      phosphorylated Aurora-A kinase marker of centrosome maturation. In contrast with
      paclitaxel-arrested cells, DPI impairs cyclin B1 accumulation. Release from DPI
      permits an accumulation of cyclin B1 and progression of the cells into mitosis.
      Conversely, exposure of paclitaxel-arrested mitotic cells to DPI causes a
      precipitous drop in cyclin B and Thr(288) phosphorylated Aurora-A levels and
      leads to mitotic catastrophe in a range of cancerous and noncancerous cells.
      Hence, the antiproliferative activity of DPI reflects a novel inhibitory
      mechanism of cell cycle progression that can reverse spindle checkpoint-mediated
      cell cycle arrest.

PMID- 15486191
TI  - The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle
      arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor
      growth in severe combined immunodeficient mice.
AB  - Anticancer effects of the dietary isothiocyanate sulforaphane were investigated
      in the human pancreatic cancer cell lines MIA PaCa-2 and PANC-1. Sulforaphane
      treated cells accumulated in metaphase as determined by flow cytometry [4C DNA
      content, cyclin A(-), cyclin B1(+), and phospho-histone H3 (Ser(10))(+)]. In
      addition, treated cells showed nuclear apoptotic morphology that coincided with
      an activation of caspase-8, loss of mitochondrial membrane potential, and loss of
      plasma membrane integrity. The initial detection of caspase-3 cleavage occurring
      in G(2)-M arrest was independent of a change in phospho-cdc2 (Tyr(15)) protein;
      consequently, sulforaphane treatment combined with UCN-01 had no significant
      impact on cellular toxicity. Incubations at higher sulforaphane doses (>10
      micromol/L) resulted in cleavage of caspase-3 in the G(1) subpopulation,
      suggesting that the induction of apoptosis and the sulforaphane-induced mitosis
      delay at the lower dose are independently regulated. Cellular toxicity in MIA
      PaCa-2, and to a greater extent in PANC-1, was positively correlated with a
      decrease in cellular glutathione levels, whereas sustained increases in
      glutathione observed in MIA PaCa-2 cells or the simultaneous incubation with N
      acetyl-L-cysteine in PANC-1 cells were associated with resistance to sulforaphane
      induced apoptosis. Daily sulforaphane i.p. injections (375 micromol/kg/d for 3
      weeks) in severe combined immunodeficient mice with PANC-1 s.c. tumors resulted
      in a decrease of mean tumor volume by 40% compared with vehicle-treated controls.
      Our findings suggest that, in addition to the known effects on cancer prevention,
      sulforaphane may have activity in established pancreatic cancer.

PMID- 15486192
TI  - Peroxisome proliferator-activated receptor gamma and retinoid X receptor ligands
      are potent inducers of differentiation and apoptosis in leukemias.
AB  - The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member of
      the nuclear receptor family that forms heterodimers with retinoid X receptor.
      These heterodimers bind to DNA and activate the transcription of target genes.
      Here, we report that the PPAR gamma receptor protein is expressed in primary
      myeloid and lymphoid leukemias and in lymphoma and myeloma cell lines. In this
      study, we compared the activity of several PPAR gamma ligands including BRL49653
      (rosiglitazone), 15-deoxy-Delta 12,14-prostaglandin J(2), and the novel
      triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid on leukemia cells.
      Exposure to these PPAR gamma ligands induced apoptosis in myeloid (U937 and HL
      60) and lymphoid (Su-DHL, Sup-M2, Ramos, Raji, Hodgkin's cell lines, and primary
      chronic lymphocytic leukemia) cells. A similar exposure to these PPAR gamma
      ligands induced the differentiation of myeloid leukemic cells. A combination of
      PPAR gamma ligands with a retinoid X receptor agonist (i.e., LG100268) or a
      retinoic acid receptor agonist (i.e., all trans-retinoic acid) enhanced
      differentiating and growth-inhibitory effects. 2-Cyano-3,12-dioxooleana-1,9-dien
      28-oic acid induced differentiation and apoptosis with much greater potency than
      the other PPAR gamma ligands in established cell lines and primary chronic
      lymphocytic leukemia samples. Exposure to 2-cyano-3,12-dioxooleana-1,9-dien-28
      oic acid induced mitochondrial depolarization and caspase activation, which was
      associated with apoptosis induction. In Bcl-2-overexpressing chronic lymphocytic
      leukemia cells, the small-molecule Bcl-2 inhibitor HA14-1 sensitized these cells
      to 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid-induced apoptosis. These results
      suggest that PPAR gamma ligation alone and in combination with retinoids holds
      promise as novel therapy for leukemias by activating the transcriptional activity
      of target genes that control apoptosis and differentiation in leukemias.

PMID- 15486193
TI  - Bortezomib rapidly suppresses ubiquitin thiolesterification to ubiquitin
      conjugating enzymes and inhibits ubiquitination of histones and type I inositol
      1,4,5-trisphosphate receptor.
AB  - The proteasome inhibitor bortezomib is an emerging anticancer agent. Although the
      proteasome is clearly its locus of action, the early biochemical consequences of
      bortezomib treatment are poorly defined. Here, we show in cultured cells that
      bortezomib and other proteasome inhibitors rapidly inhibit free ubiquitin levels
      and ubiquitin thiolesterification to ubiquitin-conjugating enzymes. Inhibition of
      thiolesterification correlated with a reduction in the ubiquitination of certain
      substrates, exemplified by a dramatic decline in histone monoubiquitination and a
      decrease in the rate of inositol 1,4,5-trisphosphate receptor polyubiquitination.
      Thus, in addition to the expected effect of blocking the degradation of
      polyubiquitinated substrates, bortezomib can also inhibit ubiquitination. The
      effect of bortezomib on histone monoubiquitination may contribute to its
      therapeutic actions.

PMID- 15486194
TI  - Genistein potentiates inhibition of tumor growth by radiation in a prostate
      cancer orthotopic model.
AB  - OBJECTIVE: We have shown previously that pretreatment with genistein potentiated
      cell killing induced by radiation in human PC-3 prostate carcinoma cell line in
      vitro. We tested this approach in vivo using an orthotopic prostate carcinoma
      model of PC-3 cells in nude mice. METHODS: Established prostate tumors were
      pretreated with p.o. genistein at a dose of 5 mg/d for 2 days followed by tumor
      irradiation with 5 Gy photons. One day after radiation, genistein was resumed and
      given every other day for 4 weeks. RESULTS: Genistein combined with radiation
      caused a significantly greater inhibition of primary tumor growth (87%) compared
      with genistein (30%) or radiation (73%) alone. The number of metastatic lymph
      nodes was also significantly decreased following genistein and radiation.
      Paradoxically, genistein alone increased the size of lymph nodes associated with
      heavy tumor infiltration. Genistein-treated prostate tumors were large with
      necrosis, apoptotic cells, and giant cells and have a lower proliferation index
      than in control tumors. Following radiation, areas of tumor destruction replaced
      by fibrotic tissue and inflammatory cells as well as giant cells were observed,
      which are typical of radiation effect. After radiation and genistein treatment,
      an increase in giant cells, apoptosis, inflammatory cells, and fibrosis was
      observed with decreased tumor cell proliferation consistent with increased tumor
      cell destruction. Long-term therapy with genistein after prostate tumor
      irradiation significantly increased survival. CONCLUSIONS: Genistein combined
      with prostate tumor irradiation led to a greater control of the growth of the
      primary tumor and metastasis to lymph nodes than genistein or radiation alone,
      resulting in greater survival.

PMID- 15486195
TI  - BimEL is an important determinant for induction of anoikis sensitivity by mitogen
      activated protein/extracellular signal-regulated kinase kinase inhibitors.
AB  - Loss of contact with substratum triggers apoptosis in many normal cell types, a
      phenomenon termed anoikis. We reported previously that mitogen-activated
      protein/extracellular signal-regulated kinase kinase (MEK) inhibitors induced
      apoptosis in nonanchored MDA-MB231 and HBC4 human breast cancer cells, whereas
      anchored cells remained viable. Here, we report that activation of the BH3-only
      protein BimEL is the major mechanism for induction of anoikis sensitivity by MEK
      inhibitors in MDA-MB231 and HBC4 cells. On treatment with MEK inhibitors, BimEL
      in MDA-MB231 and HBC4 cells rapidly increased, irrespective of the state of
      anchorage. However, it translocated to mitochondria only in nonanchored cells,
      explaining why attached cells remain viable. MDA-MB231 and HBC4 cells had
      exceedingly low basal levels of BimEL compared with other breast cancer cells,
      suggesting that maintenance of low BimEL amount is important for survival of
      these cells. MEK inhibitors also induced the electrophoretic mobility shift of
      BimEL, indicative of reduced phosphorylation. In vitro, BimEL was phosphorylated
      by extracellular signal-regulated kinase on Ser(69), which resides in the BimEL
      specific insert region. Using phosphospecific antibody against this site, we show
      that this residue is actually phosphorylated in cells. We also show that
      phosphorylation of Ser(69) promotes ubiquitination of BimEL. We conclude that MEK
      inhibitors sensitize MDA-MB231 and HBC4 cells to anoikis by blocking
      phosphorylation and hence degradation of BimEL, a mechanism that these cells
      depend on to escape anoikis.

PMID- 15486196
TI  - Inhibition of angiogenesis by growth factor receptor bound protein 2-Src homology
      2 domain bound antagonists.
AB  - Growth factor receptor bound protein 2 (Grb2) is an intracellular adaptor protein
      that participates in the signal transduction cascades of several angiogenic
      factors, including hepatocyte growth factor, basic fibroblast growth factor, and
      vascular endothelial growth factor. We described previously the potent blockade
      of hepatocyte growth factor-stimulated cell motility, matrix invasion, and
      epithelial tubulogenesis by synthetic Grb2-Src homology 2 (SH2) domain binding
      antagonists. Here, we show that these binding antagonists block basic
      morphogenetic events required for angiogenesis, including hepatocyte growth
      factor-, vascular endothelial growth factor-, and basic fibroblast growth factor
      stimulated endothelial cell proliferation and migration, as well as phorbol 12
      myristate 13-acetate-stimulated endothelial cell migration and matrix invasion.
      The Grb2-SH2 domain binding antagonists also impair angiogenesis in vitro, as
      shown by the inhibition of cord formation by macrovascular endothelial cells on
      Matrigel. We further show that a representative compound inhibits angiogenesis in
      vivo as measured using a chick chorioallantoic membrane assay. These results
      suggest that Grb2 is an important mediator of key proangiogenic events, with
      potential application to pathologic conditions where neovascularization
      contributes to disease progression. In particular, the well-characterized role of
      Grb2 in signaling cell cycle progression together with our present findings
      suggests that Grb2-SH2 domain binding antagonists have the potential to act as
      anticancer drugs that target both tumor and vascular cell compartments.

PMID- 15486197
TI  - Antiangiogenic activity of paclitaxel is associated with its cytostatic effect,
      mediated by the initiation but not completion of a mitochondrial apoptotic
      signaling pathway.
AB  - Angiogenesis is a critical event in tumor growth and metastasis, which can be
      inhibited by conventional anticancer drugs such as the microtubule-damaging agent
      paclitaxel (Taxol). In this study, we investigate the mechanism of action of
      paclitaxel on human endothelial cells. We characterize two distinct effects of
      paclitaxel on human umbilical vein endothelial cell and human microvascular
      endothelial cell-1 proliferation according to drug concentration: a cytostatic
      effect at low concentrations and a cytotoxic effect at concentrations > or =10
      nmol/L. The cytotoxic effect involves signaling pathways similar to those
      described in tumor cells (i.e., microtubule network disturbance, G(2)-M arrest,
      increase in Bax/Bcl-2 ratio, and mitochondria permeabilization) that result in
      apoptosis. In sharp contrast, the cytostatic effect involves an inhibition of
      endothelial cell proliferation without apoptosis induction and without any
      structural modification of the microtubule network. This cytostatic effect is due
      to a slowing of the cell cycle rather than to an arrest in a specific phase of
      the cell cycle. In addition, paclitaxel, at cytostatic concentrations, early
      initiates an apoptotic signaling pathway associated with increases in the
      mitochondrial reducing potential, mitochondrial membrane potential, p53
      expression, and Bax/Bcl-2 ratio. However, this apoptotic pathway is stopped
      upstream of mitochondria permeabilization and it does not lead to endothelial
      cell death. Finally, we found that paclitaxel inhibits endothelial cell
      morphogenesis on Matrigel at all tested concentrations. In conclusion, we
      describe the mechanism of action of low concentrations of paclitaxel related to
      the antiangiogenic properties of this drug.

PMID- 15486198
TI  - Targeting tumor microvessels using doxorubicin encapsulated in a novel
      thermosensitive liposome.
AB  - Liposomal drugs accumulate only in perivascular regions in tumors after i.v.
      injection. Thus, they cannot kill tumor cells in deeper tissue layers. To
      circumvent this problem, we investigated effects of doxorubicin (DOX)
      encapsulated in a lysolecithin-containing thermosensitive liposome (LTSL) on
      tumor microcirculation because damaging microvessels would stop nutrient supply
      to deeper tumor cells. We used LTSL-DOX in combination with hyperthermia to treat
      a human squamous carcinoma xenograft (FaDu) implanted in dorsal skinfold chambers
      in nude mice. Before the treatment, the RBC velocity in tumors was 0.428 +/-
      0.037 mm/s and the microvascular density was 3.93 +/- 0.44 mm/mm(2). At 24 hours
      after the treatment, they were reduced to 0.003 +/- 0.003 mm/s and 0.86 +/- 0.27
      mm/mm(2), respectively. The same treatment, however, caused only 32% decrease in
      the RBC velocity and no apparent change in microvascular networks in normal s.c.
      tissues over the same period. LTSL and LTSL-DOX alone had no effect on tumor
      microcirculation, and LTSL plus hyperthermia caused only a transient decrease in
      the RBC velocity in tumors. At 24 hours after treatments, tumor microcirculation
      in all these control experiments was insignificantly different from that before
      the treatments. We also examined apoptosis of cells in tumors at different time
      points after LTSL-DOX plus hyperthermia treatment and observed few apoptotic
      cells in tumor microvessels. In conclusion, the rapid release of DOX during
      hyperthermia could make the drug to shutdown tumor blood flow while have only
      minor effects on normal microcirculation in s.c. tissues.

PMID- 15486200
TI  - Novel peptide ligands for integrin alpha 4 beta 1 overexpressed in cancer cells.
AB  - Using the "one-bead one-peptide" combinatorial technology, a library of random
      cyclic octapeptides and nonapeptides, consisting of natural and unnatural amino
      acids, was synthesized on polystyrene beads. This library was used to screen for
      peptides that promoted attachment and proliferation of bronchioloalveolar
      carcinoma cells (H1650), employing a "cell growth on bead" assay. Consensus
      peptide sequences of cNleDXXXXc and cXNleDXXXXc (where Nle is norleucine) were
      identified. With alanine scanning and site-directed deletion, a typical ligand
      consisted of a motif of -NleDI/V/Nle- with two flanking cysteines. These peptide
      ligands were specific for promoting cell attachment of the H1650 cells and the
      cells of lymphoid cancers (Jurkat and Raji) but not other selected human cell
      lines of lung cancer and fibroblast. In an antibody blocking assay, integrin
      alpha(4)beta(1), which was overexpressed in H1650, Jurkat, and Raji, was
      identified as a putative receptor for these peptide ligands. Using Chinese
      hamster ovary cells transfected with either wild-type or mutant integrin
      alpha(4), a critical binding site for these peptides was localized to the glycine
      residue at position 190 of integrin alpha(4).

PMID- 15486199
TI  - Cells resistant to HTI-286 do not overexpress P-glycoprotein but have reduced
      drug accumulation and a point mutation in alpha-tubulin.
AB  - HTI-286, a synthetic analogue of hemiasterlin, depolymerizes microtubules and is
      proposed to bind at the Vinca peptide site in tubulin. It has excellent in vivo
      antitumor activity in human xenograft models, including tumors that express P
      glycoprotein, and is in phase II clinical evaluation. To identify potential
      mechanisms of resistance induced by HTI-286, KB-3-1 epidermoid carcinoma cells
      were exposed to increasing drug concentrations. When maintained in 4.0 nmol/L HTI
      286, cells had 12-fold resistance to HTI-286. Cross-resistance was observed to
      other Vinca peptide-binding agents, including hemiasterlin A, dolastatin-10, and
      vinblastine (7- to 28-fold), and DNA-damaging drugs, including Adriamycin and
      mitoxantrone (16- to 57-fold), but minimal resistance was seen to taxanes,
      epothilones, or colchicine (1- to 4-fold). Resistance to HTI-286 was retained
      when KB-HTI-resistant cells were grown in athymic mice. Accumulation of [(3)H]HTI
      286 was lower in cells selected in intermediate (2.5 nmol/L) and high (4.0
      nmol/L) concentrations of HTI-286 compared with parental cells, whereas
      accumulation of [(14)C]paclitaxel was unchanged. Sodium azide treatment partially
      reversed low HTI-286 accumulation, suggesting involvement of an ATP-dependent
      drug pump. KB-HTI-resistant cells did not overexpress P-glycoprotein, breast
      cancer resistance protein (BCRP/ABCG2/MXR), MRP1, or MRP3. No mutations were
      found in the major beta-tubulin isoform. However, 4.0 nmol/L HTI-286-selected
      cells had a point mutation in alpha-tubulin that substitutes Ser for Ala(12) near
      the nonexchangeable GTP-binding site of alpha-tubulin. KB-HTI-resistant cells
      removed from drug became less resistant to HTI-286, no longer had low HTI-286
      accumulation, and retained the Ala(12) mutation. These data suggest that HTI-286
      resistance may be partially mediated by mutation of alpha-tubulin and by an ATP
      binding cassette drug pump distinct from P-glycoprotein, ABCG2, MRP1, or MRP3.

PMID- 15486201
TI  - Targeting ErbB receptor signaling: a pan-ErbB approach to cancer.
AB  - The ErbB receptors are localized to the cell membrane where they are activated by
      ligand to trigger a network of signaling pathways. In some cancer cells,
      dysregulation of ErbB-mediated signaling confers a growth advantage, resulting in
      cellular transformation and increased metastatic potential. Several agents that
      inhibit individual ErbB receptors have recently been approved for the treatment
      of human malignancies, validating ErbB receptors as therapeutic targets. One
      strategy to improve the efficacy of ErbB-targeted therapies is to inhibit
      multiple ErbB receptors, thereby interfering with the cooperation that exists
      between receptors. This minireview addresses the approaches being developed to
      concurrently inhibit multiple ErbB receptors.

PMID- 15486202
TI  - Transcriptional control of SV40 T-antigen expression allows a complete reversion
      of immortalization.
AB  - Conditional proliferation of mouse embryo fibroblasts was achieved with a novel
      autoregulatory vector for Tet-dependent expression of the SV40 T-antigen. The
      majority of cell clones that were isolated under induced conditions showed strict
      regulation of cell growth. Status switches were found to be fully reversible and
      highly reproducible with respect to gene expression characteristics. A
      consequence of T-antigen expression is a significant deregulation of >400 genes.
      Deinduced cells turn to rest in G0/G1 phase and exhibit a senescent phenotype.
      The cells are not oncogenic and no evidence for transformation was found after
      several months of cultivation. Conditional immortalization allows diverse studies
      including those on cellular activities without the influence of the immortalizing
      gene(s), senescence as well as secondary effects from T-antigen expression.

PMID- 15486203
TI  - The FunCat, a functional annotation scheme for systematic classification of
      proteins from whole genomes.
AB  - In this paper, we present the Functional Catalogue (FunCat), a hierarchically
      structured, organism-independent, flexible and scalable controlled classification
      system enabling the functional description of proteins from any organism. FunCat
      has been applied for the manual annotation of prokaryotes, fungi, plants and
      animals. We describe how FunCat is implemented as a highly efficient and robust
      tool for the manual and automatic annotation of genomic sequences. Owing to its
      hierarchical architecture, FunCat has also proved to be useful for many
      subsequent downstream bioinformatic applications. This is illustrated by the
      analysis of large-scale experiments from various investigations in
      transcriptomics and proteomics, where FunCat was used to project experimental
      data into functional units, as 'gold standard' for functional classification
      methods, and also served to compare the significance of different experimental
      methods. Over the last decade, the FunCat has been established as a robust and
      stable annotation scheme that offers both, meaningful and manageable functional
      classification as well as ease of perception.

PMID- 15486204
TI  - Differential recognition by the tumor suppressor protein p53 of DNA modified by
      the novel antitumor trinuclear platinum drug BBR3464 and cisplatin.
AB  - The trinuclear platinum agent BBR3464, a representative of a new class of
      anticancer drugs, is more potent than conventional mononuclear cisplatin [cis
      diamminedichloroplatinum(II)]. BBR3464 retains significant activity in human
      tumor cell lines and xenografts that are refractory or poorly responsive to
      cisplatin, and displays a high activity in human tumor cell lines that are
      characterized by both wild-type and mutant p53 gene. In contrast, on average,
      cells with mutant p53 are more resistant to the effect of cisplatin. It has been
      hypothesized that the sensitivity or resistance of tumor cells to cisplatin might
      be also associated with cell cycle control and repair processes that involve p53.
      DNA is a major pharmacological target of platinum compounds and DNA binding
      activity of the p53 protein is crucial for its tumor suppressor function. This
      study, using gel-mobility-shift assays, was undertaken to examine the
      interactions of active and latent p53 protein with DNA fragments and
      oligodeoxyribonucleotide duplexes modified by BBR3464 in a cell free medium and
      to compare these results with those describing the interactions of these proteins
      with DNA modified by cisplatin. The results indicate that structurally different
      DNA adducts of BBR3464 and cisplatin exhibit a different efficiency to affect the
      binding affinity of the modified DNA to p53 protein. It has been suggested that
      different structural perturbations induced in DNA by the adducts of BBR3464 and
      cisplatin produce a differential response to p53 protein activation and
      recognition and that a 'molecular approach' to control of downstream effects such
      as protein recognition and pathways of apoptosis induction may consist in design
      of structurally unique DNA adducts as cell signals.

PMID- 15486205
TI  - Protein kinase CK2 phosphorylation regulates the interaction of Kaposi's sarcoma
      associated herpesvirus regulatory protein ORF57 with its multifunctional partner
      hnRNP K.
AB  - ORF57 protein of Kaposi's sarcoma-associated herpesvirus has a counterpart in all
      herpesvirus of mammals and birds and regulates gene expression at transcriptional
      and post-transcriptional levels. ORF57 was capable of self-interaction and bound
      a rapidly migrating form of heterogeneous nuclear ribonucleoprotein K (hnRNP K),
      a multifunctional cellular protein involved in gene expression. In virus infected
      cell extracts, ORF57 was present in a complex with hnRNP K that had protein
      kinase CK2 activity, and was phosphorylated by CK2. Different regions of ORF57
      bound both catalytic alpha/alpha' and regulatory beta subunits of CK2. CK2
      modification enhanced the ORF57-hnRNP K interaction, and may regulate the
      presence and activities of components in the complex. We suggest that ORF57 and
      hnRNP K interaction may modulate ORF57-mediated regulation of viral gene
      expression. Herpesviral ORF57 (Rhadinovirus) and ICP27 (Simplexvirus) proteins
      both interact with hnRNP K and CK2 implying that adaptation of the ancestral
      hnRNP K and CK2 to associate with viral regulatory ancestor protein likely pre
      dates divergence of these Herpesviridae genera that occurred 200 million years
      ago.

PMID- 15486206
TI  - DNA repair by a Rad22-Mus81-dependent pathway that is independent of Rhp51.
AB  - In budding yeast most Rad51-dependent and -independent recombination depends on
      Rad52. In contrast, its homologue in fission yeast, Rad22, was assumed to play a
      less critical role possibly due to functional redundancy with another Rad52-like
      protein Rti1. We show here that this is not the case. Rad22 like Rad52 plays a
      central role in recombination being required for both Rhp51-dependent and 
      independent events. Having established this we proceed to investigate the
      involvement of the Mus81-Eme1 endonuclease in these pathways. Mus81 plays a
      relatively minor role in the Rhp51-dependent repair of DNA damage induced by
      ultraviolet light. In contrast Mus81 has a key role in the Rad22-dependent (Rhp51
      independent) repair of damage induced by camptothecin, hydroxyurea and methyl
      methanesulfonate. Furthermore, spontaneous intrachromosomal recombination that
      gives rise to deletion recombinants is impaired in a mus81 mutant. From these
      data we propose that a Rad22-Mus81-dependent (Rhp51-independent) pathway is an
      important mechanism for the repair of DNA damage in fission yeast. Consistent
      with this we show that in vitro Rad22 can promote strand invasion to form a D
      loop that can be cleaved by Mus81.

PMID- 15486207
TI  - The sequences and activities of RegB endoribonucleases of T4-related
      bacteriophages.
AB  - The RegB endoribonuclease encoded by bacteriophage T4 is a unique sequence
      specific nuclease that cleaves in the middle of GGAG or, in a few cases, GGAU
      tetranucleotides, preferentially those found in the Shine-Dalgarno regions of
      early phage mRNAs. In this study, we examined the primary structures and
      functional properties of RegB ribonucleases encoded by T4-related bacteriophages.
      We show that all but one of 36 phages tested harbor the regB gene homologues and
      the similar signals for transcriptional and post-transcriptional autogenous
      regulation of regB expression. Phage RB49 in addition to gpRegB utilizes
      Escherichia coli endoribonuclease E for the degradation of its transcripts for
      gene regB. The deduced primary structure of RegB proteins of 32 phages studied is
      almost identical to that of T4, while the sequences of RegB encoded by phages
      RB69, TuIa and RB49 show substantial divergence from their T4 counterpart.
      Functional studies using plasmid-phage systems indicate that RegB nucleases of
      phages T4, RB69, TuIa and RB49 exhibit different activity towards GGAG and GGAU
      motifs in the specific locations. We expect that the availability of the
      different phylogenetic variants of RegB may help to localize the amino acid
      determinants that contribute to the specificity and cleavage efficiency of this
      processing enzyme.

PMID- 15486208
TI  - Venous compression at high-spatial-resolution three-dimensional MR angiography of
      peripheral arteries.
AB  - The aim of this study was to assess a venous compression technique that is
      performed with contrast material-enhanced peripheral magnetic resonance (MR)
      angiography to reduce venous enhancement. Healthy volunteers, as well as patients
      with correlating digital subtraction angiographic (DSA) findings, were examined.
      Venous compression was accomplished by placing a cuff at the midfemoral level
      unilaterally. Arterial signal-to-noise and contrast-to-noise ratios indicated no
      significant differences between compressed and noncompressed legs. Venous overlay
      was substantially reduced in the compressed legs. MR angiography with venous
      compression yielded diagnostic image quality and results that had excellent
      correlation with DSA findings. High-spatial-resolution peripheral MR angiography
      of improved diagnostic quality appears feasible, even with long data acquisition
      times.

PMID- 15486209
TI  - Osteoporotic vertebral collapse: percutaneous vertebroplasty and local kyphosis
      correction.
AB  - Forty-six cases of osteoporotic vertebral collapse (27 thoracic, 19 lumbar) were
      treated by means of percutaneous vertebroplasty in a hyperlordosis position.
      Institutional review board approval and informed consent were obtained. Kyphosis
      reducibility was preprocedurally estimated from the angular difference between
      neutral and hyperlordosis positions. Effective reduction was the angular
      difference in neutral positions before and after vertebroplasty. Reduction (< or
      =14 degrees ; mean, 6.43 degrees) was obtained in cases with estimated
      reducibility greater than 5 degrees (31 cases, 67%), which is a 34% (6.5 degrees
      of 19.1 degrees ) mean reduction. A significantly greater level of kyphosis
      reduction was observed in cases with intravertebral clefts (20 cases, 43%) at
      hyperlordosis than in those without (7.2 degrees vs 4.9 degrees ; P < .01).
      Vertebroplasty may reduce kyphosis due to localized collapsed vertebrae;
      intravertebral mobility and cleft suggest this possibility.

PMID- 15486210
TI  - Electrocardiographically gated 16-section CT of the thorax: cardiac motion
      suppression.
AB  - Thirty patients underwent 16-section multi-detector row computed tomographic (CT)
      angiography of the thorax with retrospective electrocardiographic gating.
      Institutional review board approval was obtained for retrospective analysis of CT
      scan data and records; patient informed consent was not required. Images
      reconstructed at six different time points (0%, 20%, 40%, 50%, 60%, 80%) within
      the R-R interval on the electrocardiogram were analyzed by two radiologists for
      diagnostic quality, to identify suitable reconstruction intervals for optimal
      suppression of cardiac motion. Five regions of interest (left coronary artery,
      aortic root, ascending and descending aorta, pulmonary arteries) were evaluated.
      Best image quality was achieved by referencing image reconstruction to
      middiastole (50%-60%) for the left coronary artery, aortic root, and ascending
      aorta. The pulmonary arteries are best displayed during mid- to late diastole
      (80%).

PMID- 15486211
TI  - Internal carotid artery occlusion assessed at pulsed arterial spin-labeling
      perfusion MR imaging at multiple delay times.
AB  - Magnetic resonance (MR) imaging with pulsed arterial spin labeling (ASL) was
      performed at six different inversion times in nine patients with internal carotid
      artery (ICA) occlusion and in 11 control subjects. The hospital's commission on
      scientific research on human subjects approved the study protocol, and all study
      subjects gave informed consent. Cerebral blood flow (CBF) in the middle cerebral
      artery territories was calculated from the combined signal intensities measured
      with ASL at the multiple inversion times. In the patients with ICA occlusion,
      mean CBF values were decreased in the gray matter of the hemisphere ipsilateral
      to the occlusion, as compared with values in the gray matter of the contralateral
      hemisphere (P < .05) and with values in the gray matter of the control subjects
      (P < .05). Quantification of CBF with ASL at multiple inversion times can
      compensate for the blood transit delays in patients with ICA occlusion.

PMID- 15486212
TI  - Soft-tissue lipomas: accuracy of sonography in diagnosis with pathologic
      correlation.
AB  - PURPOSE: To retrospectively determine the accuracy of sonography in helping to
      distinguish soft-tissue lipomas from other soft-tissue masses by using histologic
      proof as the reference standard. MATERIALS AND METHODS: Institutional review
      board approval was obtained, and informed consent was waived. Thirty-nine
      patients who underwent sonographic evaluation of a soft-tissue mass followed by
      biopsy or resection were retrospectively evaluated. Two musculoskeletal
      radiologists (readers 1 and 2) reviewed the sonographic images, characterized the
      masses, and rated the level of confidence in the diagnosis of lipoma by using a
      five-point scale. A level of confidence was also rated for the prospective
      sonographic report, which was reviewed and designated as reader 3. Receiver
      operating characteristic (ROC) curves, including 95% confidence intervals, were
      generated, and the area under the ROC curve (A(z)) was calculated for each
      reader. Sensitivity, specificity, and accuracy for each reader were calculated by
      using a confidence rating of 4 or 5 as positive for lipoma. Weighted kappa
      analysis was also performed to assess for interobserver variability. RESULTS:
      Histologic examination yielded 25 lipomas and 14 nonlipomas. The echogenicity of
      lipomas ranged from hypoechoic to hyperechoic relative to muscle, although most
      were isoechoic or hyperechoic. A(z) values were 0.79 for reader 1, 0.56 for
      reader 2, and 0.77 for reader 3. There was no significant difference between the
      A(z) for each reader and for chance. Interobserver agreement was fair, with a
      kappa value of 0.35 among the three readers. Sensitivities were 52%, 40%, and
      52%, and accuracies were 64%, 49%, and 64% for readers 1, 2, and 3, respectively.
      CONCLUSION: Sonography demonstrates low accuracy in the diagnosis of soft-tissue
      lipomas.

PMID- 15486213
TI  - Detection of lung cancer on radiographs: receiver operating characteristic
      analyses of radiologists', pulmonologists', and anesthesiologists' performance.
AB  - PURPOSE: To compare and quantify, by means of receiver operating characteristic
      (ROC) and localization ROC analyses, the performance of radiologists,
      pulmonologists, and anesthesiologists (residents and staff) in the detection of
      missed lung cancer. MATERIALS AND METHODS: The study was approved by the
      institutional review board, and informed consent was not required or obtained for
      review of radiographs. A set of 60 posteroanterior chest radiographs was
      presented to 36 observers: 12 radiologists, 12 pulmonologists, and 12
      anesthesiologists. Each of these three observer categories included six residents
      and six staff. Thirty of the radiographs each depicted one lung cancer that was
      overlooked at prospective image interpretation; the other 30 were normal
      radiographs matched for age and smoking history. Observers were asked to rate
      their degree of suspicion concerning the presence of lung cancer by using a
      visual analog scale and to point out the zone of suspicion on a schematic of the
      lung. These data were used to generate combined ROC-localization ROC curves and
      to assess performance. Intraobserver consistency was evaluated by using
      intraclass correlation coefficients and weighted kappa statistics. RESULTS: Areas
      under the ROC curves indicated better performance for radiologists and
      pulmonologists compared with anesthesiologists (P < .002) and for staff compared
      with residents (P < .022). Performance was lower for all categories of observers
      when localization ROC curves were used. Radiologists and staff pulmonologists
      showed a higher degree of confidence in the assessment of normality than did
      other categories of physicians. Intraobserver consistency was poor. CONCLUSION:
      Experienced readers showed better ability to distinguish normality from
      abnormality. Combined ROC and localization ROC analyses gave a more reliable
      quantification of observer performance than did ROC analysis alone.

PMID- 15486214
TI  - Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in
      preoperative assessment of breast cancer.
AB  - PURPOSE: To prospectively assess accuracy of mammography, clinical examination,
      ultrasonography (US), and magnetic resonance (MR) imaging in preoperative
      assessment of local extent of breast cancer. MATERIALS AND METHODS: Institutional
      review board approval and informed patient consent were obtained. Results of
      bilateral mammography, US, and contrast-enhanced MR imaging were analyzed from
      111 consecutive women with known or suspected invasive breast cancer. Results
      were correlated with histopathologic findings. RESULTS: Analysis included 177
      malignant foci in 121 cancerous breasts, of which 89 (50%) foci were palpable.
      Median size of 139 invasive foci was 18 mm (range, 2-107 mm). Mammographic
      sensitivity decreased from 100% in fatty breasts to 45% in extremely dense
      breasts. Mammographic sensitivity was highest for invasive ductal carcinoma (IDC)
      in 89 of 110 (81%) cases versus 10 of 29 (34%) cases of invasive lobular
      carcinoma (ILC) (P < .001) and 21 of 38 (55%) cases of ductal carcinoma in situ
      (DCIS) (P < .01). US showed higher sensitivity than did mammography for IDC,
      depicting 104 of 110 (94%) cases, and for ILC, depicting 25 of 29 (86%) cases (P
      < .01 for each). US showed higher sensitivity for invasive cancer than DCIS (18
      of 38 [47%], P < .001). MR showed higher sensitivity than did mammography for all
      tumor types (P < .01) and higher sensitivity than did US for DCIS (P < .001),
      depicting 105 of 110 (95%) cases of IDC, 28 of 29 (96%) cases of ILC, and 34 of
      38 (89%) cases of DCIS. In anticipation of conservation or no surgery after
      mammography and clinical examination in 96 breasts, additional tumor (which
      altered surgical approach) was present in 30. Additional tumor was depicted in 17
      of 96 (18%) breasts at US and in 29 of 96 (30%) at MR, though extent was now
      overestimated in 12 of 96 (12%) at US and 20 of 96 (21%) at MR imaging. After
      combined mammography, clinical examination, and US, MR depicted additional tumor
      in another 12 of 96 (12%) breasts and led to overestimation of extent in another
      six (6%); US showed no detection benefit after MR imaging. Bilateral cancer was
      present in 10 of 111 (9%) patients; contralateral tumor was depicted
      mammographically in six and with both US and MR in an additional three. One
      contralateral cancer was demonstrated only clinically. CONCLUSION: In nonfatty
      breasts, US and MR imaging were more sensitive than mammography for invasive
      cancer, but both MR imaging and US involved risk of overestimation of tumor
      extent. Combined mammography, clinical examination, and MR imaging were more
      sensitive than any other individual test or combination of tests.

PMID- 15486215
TI  - Moderate versus high concentration of contrast material for aortic and hepatic
      enhancement and tumor-to-liver contrast at multi-detector row CT.
AB  - PURPOSE: To prospectively evaluate aortic and hepatic enhancement and depiction
      of hypervascular hepatocellular carcinoma (HCC) between two contrast materials
      with moderate and high iodine concentrations when administered at same iodine
      dose and injection duration at multi-detector row helical computed tomography
      (CT). MATERIALS AND METHODS: Institutional review board approval and informed
      patient consent were obtained. One hundred eighty-six patients were studied, and
      67 patients with hypervascular HCC were identified. Ninety-four patients were
      assigned to receive iohexol 350 (mg iodine per milliliter) with protocol A; 92,
      iohexol 300 with protocol B. In both protocols, iohexol with same iodine load per
      weight (518 mg/kg) was administered with same injection duration (25 seconds).
      Multiphase CT scanning was started 10, 20, 50, and 180 seconds after the trigger
      (threshold level set at increase of 100 HU over baseline CT number of aorta).
      Enhancement of aorta and liver was measured in 186 patients. Tumor-to-liver
      contrast was measured in 67 patients with hypervascular HCC. Statistical analysis
      was performed with Mann-Whitney U test. RESULTS: Medians of aortic enhancement
      during four phases were 325, 185, 112, and 69 HU with protocol A. Corresponding
      values were 344, 266, 121, and 73 HU with protocol B. During all phases, aortic
      enhancement was significantly higher with protocol B (P = .046, P < .001, P <
      .001, and P = .002). Hepatic enhancement during four phases was 6, 21, 48, and 34
      HU with protocol A. Corresponding values were 3, 17, 47, and 35 HU with protocol
      B. Hepatic enhancement was significantly higher with protocol A during first and
      second phases (P < .001 for both), although there was no significant difference
      between protocols during third and fourth phases (P = .778 and P = .178,
      respectively). Medians of tumor-to-liver contrast during four phases were 22, 34,
      0.5, and -1.1 HU with protocol A. Corresponding values were 23, 45, 0, and -8.6
      HU with protocol B. Tumor-to-liver contrast was significantly higher with
      protocol B during second phase (P = .049), although there was no difference
      between protocols during other phases. CONCLUSION: When total iodine dose was
      adjusted to body weight and injection duration was fixed, rapid administration of
      moderate concentration of contrast material was more effective for depiction of
      hypervascular HCC than was high concentration of contrast material.

PMID- 15486216
TI  - In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal
      stem cells in rat kidney and liver.
AB  - PURPOSE: To evaluate in vivo magnetic resonance (MR) imaging with a conventional
      1.5-T system for depiction and tracking of intravascularly injected
      superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs).
      MATERIALS AND METHODS: This study was conducted in accordance with French law
      governing animal research and met guidelines for animal care and use. Rat MSCs
      were labeled with SPIO and transfection agent. Relaxation rates at 1.5 T, cell
      viability, proliferation, differentiation capacity, and labeling stability were
      assessed in vitro as a function of SPIO concentration. MSCs were injected into
      renal arteries of healthy rats (labeled cells in four, unlabeled cells in two)
      and portal veins of rats treated with carbon tetrachloride to induce
      centrolobular liver necrosis (labeled cells and unlabeled cells in two each).
      Follow-up serial T2*-weighted gradient-echo MR imaging and R2* mapping were
      performed. MR imaging findings were compared histologically. RESULTS: SPIO
      labeling caused a strong R2* effect that increased linearly with iron dose; R2*
      increase for cells labeled for 48 hours with 50 microg of iron per milliliter was
      50 sec(-1) per million cells per milliliter. R2* was proportional to iron load of
      cells. SPIO labeling did not affect cell viability (P > .27). Labeled cells were
      able to differentiate into adipocytes and osteocytes. Proliferation was
      substantially limited for MSCs labeled with 100 microg Fe/mL or greater. Label
      half-life was longer than 11 days. In normal kidneys, labeled MSCs caused signal
      intensity loss in renal cortex. After labeled MSC injection, diseased liver had
      diffuse granular appearance. Cells were detected for up to 7 days in kidney and
      12 days in liver. Signal intensity loss and fading over time were confirmed with
      serial R2* mapping. At histologic analysis, signal intensity loss correlated with
      iron-loaded cells, primarily in renal glomeruli and hepatic sinusoids;
      immunohistochemical analysis results confirmed these cells were MSCs. CONCLUSION:
      MR imaging can aid in monitoring of intravascularly administered SPIO-labeled
      MSCs in vivo in kidney and liver.

PMID- 15486217
TI  - Follow-up of palpable circumscribed noncalcified solid breast masses at
      mammography and US: can biopsy be averted?
AB  - PURPOSE: To determine whether palpable noncalcified solid breast masses with
      benign morphology at mammography and ultrasonography (US) can be managed
      similarly to nonpalpable probably benign lesions (Breast Imaging Reporting and
      Data System [BI-RADS] category 3)-that is, with periodic imaging surveillance-and
      to determine whether biopsy can be averted in these lesions. MATERIALS AND
      METHODS: No institutional review board approval or patient consent was required.
      This retrospective analysis, based on final imaging reports, included 152
      patients (age range, 28-77 years; mean age, 48.3 years) with 157 palpable
      noncalcified solid masses that were classified as probably benign at initial
      mammography and US. Of 152 patients, 108 underwent follow-up with mammography and
      US (6-month intervals for 2 years, then 12-month intervals). The remaining 44
      patients underwent surgical or needle biopsy after initial imaging. Lesions were
      analyzed at initial and follow-up examinations. Statistical analysis included
      Student t test and corresponding exact 95% confidence intervals. RESULTS: In 108
      patients who underwent follow-up only, 112 lesions were palpable. In 102 (94.4%)
      of 108 patients, masses remained stable during follow-up. Lesions were followed
      for at least 2 years (mean, 4.1 years; range, 2-7 years). In six (5.6%) patients,
      palpable lesions increased in size during follow-up; these lesions were benign at
      subsequent open biopsy. No breast carcinoma was diagnosed in the 44 patients with
      45 palpable lesions who underwent biopsy after initial imaging. Of 157 lesions,
      no malignant tumors were observed (exact one-sided 95% confidence interval: 0%,
      1.95%). CONCLUSION: The data strongly suggest that palpable noncalcified solid
      breast masses with benign morphology at mammography and US can be managed
      similarly to nonpalpable BI-RADS category 3 lesions, with short-term follow-up (6
      month intervals for 2 years). More data, based on a larger series, are required
      to determine whether this conclusion is correct.

PMID- 15486218
TI  - Bronchial and nonbronchial systemic arteries at multi-detector row CT
      angiography: comparison with conventional angiography.
AB  - PURPOSE: To retrospectively evaluate bronchial and nonbronchial systemic arteries
      at multi-detector row helical computed tomography (CT) compared with conventional
      angiography in patients undergoing endovascular treatment of hemoptysis.
      MATERIALS AND METHODS: Neither institutional board approval nor informed consent
      was required. Forty-eight consecutive patients (39 men, nine women; mean age,
      55.7 years; range, 20-82 years) with hemoptysis of bronchial and nonbronchial
      systemic artery origin underwent multi-detector row helical CT angiography of the
      thorax with use of a four-detector row (n = 31) or 16-detector row (n = 17)
      scanner prior to embolization. Findings on CT angiograms, including CT scans,
      maximum intensity projections, and three-dimensional volume-rendered images, were
      used to evaluate the depiction of bronchial and nonbronchial systemic arteries.
      Retrospective analysis of the ostium and the course of bronchial and/or
      nonbronchial systemic arteries on CT angiograms enabled evaluation of the
      accuracy of this technique in identification of the relevant vasculature.
      RESULTS: Among the 46 patients initially treated with bronchial artery
      embolization, 58 bronchial arteries were identified at CT and/or angiography. In
      50 (86%) cases, concordant findings were observed with both modalities. In five
      (9%) cases, CT could not be used to identify the ostia of bronchial arteries. In
      three (5%) cases, CT depicted bronchial arteries that could not be selectively
      catheterized. Three-dimensional images were found to be superior to transverse CT
      scans in depicting the ectopic origin of the bronchial arteries, which enabled
      the interventional radiologists to perform successful embolization after direct
      catherization of the ectopic vessel in every case. In five (11%) patients, the
      nonbronchial systemic origin of bronchial bleeding was identified on CT
      angiograms. CONCLUSION: Multi-detector row helical CT angiography provides more
      precise depiction of bronchial and nonbronchial systemic arteries than does
      conventional angiography.

PMID- 15486219
TI  - Live view of gonadotropin-releasing hormone containing neuron migration.
AB  - Neurons that synthesize GnRH control the reproductive axis and migrate over long
      distances and through different environments during development. Prior studies
      provided strong clues for the types of molecules encountered and movements
      expected along the migratory route. However, our studies provide the first real
      time views of the behavior of GnRH neurons in the context of an in vitro
      preparation that maintains conditions comparable to those in vivo. The live views
      provide direct evidence of the changing behavior of GnRH neurons in their
      different environments, showing that GnRH neurons move with greater frequency and
      with more changes in direction after they enter the brain. Perturbations of
      guiding fibers distal to moving GnRH neurons in the nasal compartment influenced
      movement without detectable changes in the fibers in the immediate vicinity of
      moving GnRH neurons. This suggests that the use of fibers by GnRH neurons for
      guidance may entail selective signaling in addition to mechanical guidance. These
      studies establish a model to evaluate the influences of specific molecules that
      are important for their migration.

PMID- 15486220
TI  - The 17alpha and 17beta isomers of estradiol both induce rapid spine synapse
      formation in the CA1 hippocampal subfield of ovariectomized female rats.
AB  - Previous studies have demonstrated that estradiol-17beta and estradiol-17alpha
      both induce short-latency effects on spatial memory in rats, estradiol-17alpha
      being at least as potent as its 17beta isomer. To determine whether the
      mechanisms underlying these behavioral responses might include effects on
      hippocampal synaptic plasticity, CA1 pyramidal spine synapse density (PSSD) was
      measured in ovariectomized rats within the first few hours after s.c. estrogen
      injection. PSSD increased markedly (by 24%) 4.5 h after the administration of 45
      microg/kg estradiol-17beta. The PSSD response was significantly greater (44%
      above control) 30 min after estradiol-17beta injection and was markedly dose
      dependent; a 3-fold lower estradiol-17beta dose (15 microg/kg) did not
      significantly affect CA1 PSSD at either 30 min or 4.5 h. Estradiol-17alpha was a
      more potent inducer of PSSD than estradiol-17beta. Dose-response analysis
      determined an ED50 for the effect of estradiol-17alpha on PSSD of 8.92 +/- 1.99
      microg/kg, with a maximal response at 15 microg/kg. These results demonstrate
      that high doses of estradiol induce rapid changes in CA1 PSSD. CA1 spine synapse
      formation appears to be more sensitive to estradiol-17alpha than to estradiol
      17beta, paralleling previous data on the effects of these two steroids on spatial
      memory. Rapid remodeling of hippocampal synaptic connections may thus contribute
      to the enhancement of spatial mnemonic processing observed within the first few
      hours after estrogen treatment. The potency of estradiol-17alpha suggests that
      hormone replacement therapy using this steroid might be useful clinically in
      ameliorating the impact of low endogenous estrogen production on the development
      and progression of neurodegenerative disorders involving the hippocampus.

PMID- 15486221
TI  - Stimulation of luteinizing hormone-releasing hormone (LHRH) gene expression in
      GT1-7 cells by its metabolite, LHRH-(1-5).
AB  - Given the central role of the decapeptide LHRH in reproduction and reproductive
      behavior, it is important to focus on delineating the possible effects of this
      gene and its products in the regulation of hormone-dependent reproductive
      processes. In the female, ovulation is preceded by a marked increase in LHRH
      release; the increase in LHRH release culminates in a preovulatory LH surge,
      which coincides with a period of sexual receptivity. In contrast to the belief
      that the proteolytic metabolism of LHRH serves only as a degradative process that
      removes excess LHRH and attenuates signal transduction through the LHRH receptor,
      we hypothesized that a metabolite of the decapeptide, LHRH-(1-5), can directly
      regulate LHRH neuronal function. This study demonstrates the ability of LHRH-(1
      5) peptide to regulate LHRH gene expression in the LHRH neuronal cell line, the
      GT(1-7) cell. The results show that LHRH-(1-5) stimulated LHRH gene expression at
      the posttranscriptional level. In contrast to the LHRH suppression of its own
      gene expression, the coadministration of LHRH with the metalloendopeptidase, EC
      3.4.24.15, an endopeptidase known to cleave LHRH to form LHRH(1-5), shows a
      reversal of effect, a stimulation of LHRH gene expression. Finally, the effect of
      LHRH-(1-5) on LHRH gene expression appears to be mediated by the
      calcium/calmodulin-dependent protein kinase. The present study supports the
      hypothesis that the physiological metabolite of LHRH, LHRH-(1-5), is functionally
      capable of regulating the reproductive neuroendocrine system.

PMID- 15486222
TI  - Stimulation of catecholamine synthesis by environmental estrogenic pollutants.
AB  - Environmental estrogenic pollutants are compounds that have been shown to have
      estrogenic effects on fetal development and reproductive systems. Less attention,
      however, has been paid to their influence on neuronal functions. We report here
      the effects of estrogenic pollutants on catecholamine synthesis in bovine adrenal
      medullary cells used as a model system of noradrenergic neurons. Treatment of
      cultured bovine adrenal medullary cells with p-nonylphenol and bisphenol A at 10
      nM for 3 d stimulated [14C]catecholamine synthesis from [14C]tyrosine and
      tyrosine hydroxylase activity, an effect that was not inhibited by ICI 182,780,
      an antagonist of estrogen receptors. Significant effects of p-nonylphenol on
      [14C]catecholamine synthesis were observed at 0.1 nM, which is 45 times lower
      than that of the international regulatory standard (4.5 nM), and the maximum
      effects were around 10-100 nM. The concentrations (0.1-10 nM) used in the present
      study are similar to the range observed in rivers in the United States or Europe.
      On the other hand, short-term treatment of cells with 10 nM p-nonylphenol for 10
      min also activated tyrosine hydroxylase, which was suppressed by U0126, an
      inhibitor of MAPK kinase. Furthermore, treatment of cells with p-nonylphenol for
      5 min increased the phospho-p44/42MAPK in a concentration-dependent (1-1000 nM)
      manner, whereas p-nonylphenol (100 nm, 2 d) enhanced both levels of non-phospho-
      and phospho-p44/42MAPK. These findings suggest that short-term and long-term
      treatment of cells with estrogenic pollutants at environmental concentrations
      stimulates catecholamine synthesis and MAPK through an estrogen receptor
      independent pathway.

PMID- 15486223
TI  - Stimulation of steroidogenesis in immature rat Leydig cells evoked by interleukin
      1alpha is potentiated by growth hormone and insulin-like growth factors.
AB  - The cytokine IL-1alpha is produced constitutively by the intact testis, but its
      function in this organ remains largely unknown. In this study we examined
      cooperation between IL-1alpha and GH and IGFs with regard to stimulation of
      steroidogenesis by Leydig cells from 40-d-old rats in vitro. IL-1alpha alone
      stimulated testosterone (T) and dihydrotestosterone (DHT) production. GH, IGF-I,
      or IGF-II alone was without effect on T production, but they were found to
      elevate DHT release, albeit without an obvious dose-response effect.
      Costimulation with IL-1alpha and GH or with IL-1alpha and IGF-I or IGF-II
      elevated the rate of steroidogenesis (both T and DHT) above that observed with IL
      1alpha alone. GH was found to increase the level of IGF-I in the cultured Leydig
      cells, an effect that was potentiated by IL-1alpha. The costimulatory effect of
      GH on steroidogenesis was abolished by treatment with picropodophyllin, a
      specific inhibitor of the IGF-I receptor, indicating that the action of GH is
      mediated via IGF-I. Moreover, cells costimulated with IL-1alpha and GH exhibited
      a marked decrease in the level of intact IGF-binding protein-3 in the culture
      medium due to the induction of proteolytic activity toward this binding protein.
      In contrast, secretion of IGF-binding protein-2 was increased by such
      costimulation. These findings suggest that the stimulation of steroidogenesis in
      Leydig cells evoked by GH and IGFs requires cooperation with IL-1alpha. This
      cooperation may play an important role in connection with postnatal Leydig cell
      maturation and steroidogenesis.

PMID- 15486224
TI  - Modification of the terminal residue of apelin-13 antagonizes its hypotensive
      action.
AB  - The apelin peptide is the endogenous ligand for the apelin G protein-coupled
      receptor. The distribution of the apelin peptides and receptor are widespread in
      the central nervous system and periphery, with reported roles in the hypothalamic
      pituitary-adrenal axis, blood pressure regulation and as one of the most potent
      positive inotropic substances yet identified. In this report, we show that in
      native tissues preproapelin exists as a dimer. Dimeric preproapelin was reduced
      to monomers by dithiothreitol treatment, indicating disulfide linkages. To
      evaluate the role of the carboxyl-terminal phenylalanine in the hypotensive
      action of apelin-13, analogs were generated and tested for their role on blood
      pressure regulation. Injections of apelin-13 and apelin-12 (15 microg/kg) into
      spontaneously hypertensive rats lowered systolic and diastolic blood pressure to
      result in decreases of approximately 60% and 15% in mean arterial blood pressure,
      respectively. Apelin-13(13[D-Phe]) treatment did not differ from apelin-13 in
      either efficacy or duration of effect, whereas apelin-13(F13A) revealed a loss of
      function. However, concomitant administration of apelin-13(F13A) (30 microg/kg)
      blocked hypotensive effects of apelin-13 (15 microg/kg), which revealed that
      apelin-13(F13A) behaved as an apelin-specific antagonist.

PMID- 15486225
TI  - Cell-specific expression of glucose-dependent-insulinotropic polypeptide is
      regulated by the transcription factor PDX-1.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) is a potent stimulator of
      insulin secretion and comprises an important component of the enteroinsular axis.
      GIP is synthesized in enteroendocrine K-cells located principally in the upper
      small intestine. The homeobox-containing gene PDX-1 is also expressed in the
      small intestine and plays a critical role in pancreatic development and in the
      expression of pancreatic-specific genes. Previous studies determined that the
      transcription factors GATA-4 and ISL-1 are important for GIP expression. In this
      study, we demonstrate that PDX-1 is also involved in regulating GIP expression in
      K-cells. Using immunohistochemistry, we verified the expression of PDX-1 protein
      in the nucleus of GIP-expressing mouse K-cells and evaluated the expression of
      PDX-1, serotonin, and GIP in wild-type and PDX-1(-/-) mice at 18.5 d after
      conception. Although we demonstrated a 97.8% reduction in the number of GIP
      expressing cells in PDX-1(-/-) mice; there was no statistical difference in the
      number of serotonin-positive cells. Additionally, PDX-1 transcripts and protein
      were detected in a GIP-expressing neuroendocrine cell line, STC-1.
      Electromobility shift assays using STC-1 nuclear extracts demonstrated the
      specific binding of PDX-1 protein to a specific regulatory region in the GIP
      promoter. Using chromatin immunoprecipitation analysis, we demonstrated binding
      of PDX-1 to this same region of the GIP promoter in intact cells. Lastly,
      overexpression of PDX-1 in transient transfection assays led to a specific
      increase in the activity of GIP/Luc reporter constructs. The results of these
      studies indicate that the transcription factor PDX-1 plays a critical role in the
      cell-specific expression of the GIP gene.

PMID- 15486226
TI  - 11-deoxycorticosterone is a potent agonist of the rainbow trout (Oncorhynchus
      mykiss) mineralocorticoid receptor.
AB  - The teleost fish are thought to lack the mineralocorticoid hormone aldosterone
      but possess mineralocorticoid receptor (MR) homologs. Here we describe the
      characterization of two rainbow trout (Oncorhynchus mykiss) MRs, called rtMRa and
      rtMRb. The open reading frame of rtMRa cDNA encoded a protein of 1041 amino
      acids. The rtMRb predicted protein sequence is similar, differing in only 10
      amino acids in the nonconserved A/B domain and lacking a three-amino acid
      insertion between the two zinc fingers of the C domain. Expression of rtMR mRNA
      (sum of both forms), measured in juvenile trout by real-time RT-PCR, shows that
      the transcripts are ubiquitous. Expression was significantly higher in brain than
      the other tissues studied (eye, trunk kidney, head kidney, gut, gills, liver,
      spleen, ovary, heart, white muscle, skin). Hormonal stimulation of receptor
      transactivation activity was studied in COS-7 cells transiently cotransfected
      with receptor cDNA and a mouse mammary tumor virus-luciferase reporter. The
      mineralocorticoids 11-deoxycorticosterone and aldosterone were more potent
      enhancers of rtMRa transcriptional activity (EC50 = 1.6 +/- 0.5 x 10(-10) and 1.1
      +/- 0.4 x 10(-10) M, respectively) than the glucocorticoids cortisol and 11
      deoxycortisol (EC50 = 1.1 +/- 0.3 x 10(-9) and 3.7 +/- 1.9 x 10(-9) M,
      respectively). A similar response was observed in transactivation assays with
      rtMRb. These results are discussed in the view of reported circulating levels of
      corticosteroids in trout.

PMID- 15486227
TI  - Identification of a stanniocalcin paralog, stanniocalcin-2, in fish and the
      paracrine actions of stanniocalcin-2 in the mammalian ovary.
AB  - Stanniocalcin is a glycoprotein hormone important in the maintenance of calcium
      and phosphate homeostasis in fish. Two related mammalian stanniocalcin genes,
      STC1 and STC2, were found to be expressed in various tissues as paracrine
      regulators. We have demonstrated the existence of a second stanniocalcin gene in
      fish, designated fish STC2, with only 30% identity to fish STC1. However,
      phylogenetic analysis and comparison of the genomic structure of STC genes in
      vertebrates indicated that STC1 and STC2 genes were probably derived from a
      common ancestor gene. Based on the prominent expression of mammalian STC1 in the
      ovary, we tested STC2 expression in rat ovary and the regulation of STC2
      expression by gonadotropins. Treatment of immature rats with pregnant mare serum
      gonadotropin increased STC2 transcripts, whereas subsequent treatment with human
      chorionic gonadotropin suppressed STC2 expression. Real-time PCR analyses also
      demonstrated that STC2 is expressed mainly in thecal layers. In situ
      hybridization studies also revealed that STC2 is expressed in thecal cell layers
      of antral and preovulatory follicles after gonadotropin stimulation. To elucidate
      the physiological functions of STC2, recombinant human and fish STC2 proteins
      were generated and found to be N-glycosylated homodimers. In cultured granulosa
      cells, treatment with human or fish STC2 suppressed FSH-induced progesterone, but
      not estradiol or cAMP, production. The STC2 suppression of progesterone
      production was associated with the inhibition of FSH-induced CYP11A and 3beta
      hydroxysteroid dehydrogenase expression. Thus, STC2 is a functional homodimeric
      glycoprotein, and thecal cell-derived STC2 could play a paracrine role during
      follicular development.

PMID- 15486228
TI  - Intestinal lipoprotein overproduction, a newly recognized component of insulin
      resistance, is ameliorated by the insulin sensitizer rosiglitazone: studies in
      the fructose-fed Syrian golden hamster.
AB  - We investigated whether intestinal lipoprotein overproduction in a fructose-fed,
      insulin-resistant hamster model is prevented with insulin sensitization. Syrian
      Golden hamsters were fed either chow, 60% fructose for 5 wk, chow for 5 wk with
      the insulin sensitizer rosiglitazone added for the last 3 wk, or 60% fructose
      plus rosiglitazone. In vivo Triton studies showed a 2- to 3-fold increase in the
      large (Svedberg unit > 400) and smaller (Sf 100-400) triglyceride-rich
      lipoprotein particle apolipoprotein B48 (apoB48) but not triglyceride secretion
      with fructose feeding in the fasted state (P < 0.01) and partial normalization
      with rosiglitazone in fructose-fed hamsters. Ex vivo pulse-chase labeling of
      enterocytes confirmed the oversecretion of apoB48 lipoproteins with fructose
      feeding. Intestinal lipoprotein oversecretion was associated with increased
      expression of microsomal triglyceride transfer protein expression. With
      rosiglitazone treatment of fructose-fed hamsters, there was approximately 50%
      reduction in apoB48 secretion from primary cultured enterocytes and amelioration
      of the elevated microsomal triglyceride transfer protein mass and activity in
      fructose-fed hamsters. In contrast, in the postprandial state, the major
      differences between nutritional and drug intervention protocols were evident in
      triglyceride-rich lipoprotein triglyceride and not apoB48 secretion rates. The
      data suggest that intestinal lipoprotein overproduction can be ameliorated with
      the insulin sensitizer rosiglitazone.

PMID- 15486229
TI  - Glucagon-like peptide 2 dose-dependently activates intestinal cell survival and
      proliferation in neonatal piglets.
AB  - Glucagon-like peptide 2 (GLP-2) is a gut hormone that stimulates mucosal growth
      in total parenteral nutrition (TPN)-fed piglets; however, the dose-dependent
      effects on apoptosis, cell proliferation, and protein synthesis are unknown. We
      studied 38 TPN-fed neonatal piglets infused iv with either saline or GLP-2 at
      three rates (2.5, 5.0, and 10.0 nmol.kg(-1).d(-1)) for 7 d. Plasma GLP-2
      concentrations ranged from 177 +/- 27 to 692 +/- 85 pM in the low- and high
      infusion groups, respectively. GLP-2 infusion dose-dependently increased small
      intestinal weight, DNA and protein content, and villus height; however, stomach
      protein synthesis was decreased by GLP-2. Intestinal crypt and villus apoptosis
      decreased and crypt cell number increased linearly with GLP-2 infusion rates,
      whereas cell proliferation and protein synthesis were stimulated only at the high
      GLP-2 dose. The intestinal activities of caspase-3 and -6 and active caspase-3
      abundance decreased, yet procaspase-3 abundance increased markedly with
      increasing infusion rate and plasma concentration of GLP-2. The GLP-2-dose
      dependent suppression of intestinal apoptosis and caspase-3 activity was
      associated with increased protein kinase B and glycogen-synthase kinase-3
      phosphorylation, yet the expression phosphatidylinositol 3-kinase was unaffected
      by GLP-2. Intestinal endothelial nitric oxide synthase mRNA and protein
      expression was increased, but only at the high GLP-2 dose. We conclude that the
      stimulation of intestinal epithelial survival is concentration dependent at
      physiological GLP-2 concentrations; however, induction of cell proliferation and
      protein synthesis is a pharmacological response. Moreover, we show that GLP-2
      stimulates intestinal cell survival and proliferation in association with
      induction of protein kinase B and glycogen-synthase kinase-3 phosphorylation and
      Bcl-2 expression.

PMID- 15486230
TI  - The role of the locus coeruleus in corticotropin-releasing hormone and stress
      induced suppression of pulsatile luteinizing hormone secretion in the female rat.
AB  - Despite a wealth of evidence for CRH mediating stress-induced suppression of the
      hypothalamic GnRH pulse generator, and hence reproductive dysfunction, the site
      and mechanism of action remains elusive. The locus coeruleus (LC), a prominent
      noradrenergic brain stem nucleus, is innervated by CRH neurons, mediates several
      behavioral stress responses, and is implicated in the control of pulsatile LH
      secretion. The aim of this study was to test the hypothesis that LC CRH has a
      critical role in mediating stress-induced suppression of pulsatile LH secretion
      in the rat. Ovariectomized rats with 17beta-estradiol or oil-filled s.c. capsules
      were implanted with bilateral LC and i.v. cannulae. Central administration of CRH
      (10 ng to 1 microg) resulted in a dose-dependent suppression of LH pulses, which
      was reversed by a CRH receptor antagonist (alpha-helical CRF(9-41), 1 microg).
      The induction of c-fos expression in glutamic acid decarboxylase67 immunostained
      neurons in the preoptic area suggests activation of the secretion of gamma
      aminobutyric acid in response to intracoerulear administration of CRH; 17beta
      estradiol further increased the percentage of glutamic acid decarboxylase67
      positive neurons that expressed fos and augmented suppression of LH pulses.
      Furthermore, intracoerulear administration of alpha-helical CRF(9-41) completely
      blocked restraint stress-induced suppression of LH pulses, without affecting the
      inhibitory response to hypoglycemia. These results suggest that CRH innervation
      of the LC may play a pivotal, but differential, role in the normal physiological
      response of stress-induced suppression of the GnRH pulse generator and hence the
      reproductive system.

PMID- 15486231
TI  - Spatial reorganization of glycogen synthase upon activation in 3T3-L1 adipocytes.
AB  - The dephosphorylation of glycogen synthase is a key step in the stimulation of
      glycogen synthesis by insulin. To further investigate the hormonal regulation of
      glycogen synthase activity, enzymatic localization in 3T3-L1 adipocytes was
      determined by immunocytochemistry and confocal microscopy. In basal cells,
      glycogen synthase and the protein phosphatase-1-glycogen-targeting subunit,
      protein targeting to glycogen (PTG), were diffusely distributed throughout the
      cell. Insulin treatment had no effect on PTG distribution but resulted in a
      reorganization of glycogen synthase into punctate clusters. Glycogen synthase
      aggregation was restricted to discrete cellular sites, presumably where glycogen
      synthesis occurred. Omission of extracellular glucose or substitution with 2
      deoxy-glucose blocked the insulin-induced redistribution of glycogen synthase.
      Addition of the glycogenolytic agent forskolin after insulin stimulation
      disrupted the clusters of glycogen synthase protein, restoring the immunostaining
      pattern to the basal state. Conversely, adenoviral-mediated overexpression of PTG
      resulted in the insulin-independent dephosphorylation of glycogen synthase and a
      redistribution of the enzyme from the cytosolic- to glycogen-containing
      fractions. The effects of PTG on glycogen synthase activity were mediated by
      multisite dephosphorylation, which was enhanced by insulin and 2-deoxy-glucose,
      and required a functional glycogen synthase-binding domain on PTG. However, PTG
      overexpression did not induce distinct glycogen synthase clustering in fixed
      cells, presumably because cellular glycogen levels were increased more than 7
      fold under these conditions, resulting in a diffusion of sites where glycogen
      elongation occurred. Cumulatively, these data indicate that the hormonal
      regulation of glycogen synthesis rates in 3T3-L1 adipocytes is mediated in part
      through changes in the subcellular localization of glycogen synthase.

PMID- 15486232
TI  - The orphan nuclear receptors NURR1 and NGFI-B modulate aromatase gene expression
      in ovarian granulosa cells: a possible mechanism for repression of aromatase
      expression upon luteinizing hormone surge.
AB  - Ovarian granulosa cells play pivotal roles in many aspects of ovary functions
      including folliculogenesis and steroidogenesis. In response to FSH and LH, the
      elevation of intracellular cAMP level in granulosa cells leads to activation of
      multiple ovarian genes. Here, we report findings from a genome-wide study of the
      cAMP-responsive gene expression profiles in a human granulosa-like tumor cell
      line, KGN. The study identified 140 genes that are either activated or repressed
      by 2-fold or greater after stimulation by the adenylyl cyclase activator
      forskolin. The induction patterns of some cAMP-responsive genes were further
      analyzed by quantitative real-time PCR. Consistent with previous observations,
      the LH-responsive genes, such as the nuclear receptor 4A subfamily (NURR1, NGFI
      B, and NOR-1), were rapidly but transiently induced, whereas the FSH-responsive
      gene CYP19 encoding aromatase was induced in a delayed fashion. Interestingly,
      ectopic expression of NURR1 or NGFI-B severely attenuated the cAMP-responsive
      activation of the ovary-specific aromatase promoter. Reduction of the endogenous
      NURR1 or NGFI-B by small interfering RNA significantly elevated aromatase gene
      expression. The cis-elements responsible for NURR1/NGFI-B-mediated repression
      were mapped to the minimal aromatase promoter sequence that confers camp
      responsiveness. Furthermore, the DNA-binding domain of NURR1 was required for the
      repression. Taken together, these results strongly suggest a causal relationship
      between the rapid decline of aromatase mRNA and induction of nuclear receptor
      subfamily 4A expression, which concomitantly occur upon LH surge at the later
      stages of ovarian follicular development.

PMID- 15486233
TI  - Hypophysiotropic thyrotropin-releasing hormone and corticotropin-releasing
      hormone neurons of the rat contain vesicular glutamate transporter-2.
AB  - TRH and CRH are secreted into the hypophysial portal circulation by
      hypophysiotropic neurons located in parvicellular subdivisions of the
      hypothalamic paraventricular nucleus (PVH). Recently these anatomical
      compartments of the PVH have been shown to contain large numbers of glutamatergic
      neurons expressing type 2 vesicular glutamate transporter (VGLUT2). In this
      report we presented dual-label in situ hybridization evidence that the majority
      (>90%) of TRH and CRH neurons in the PVH of the adult male rat express the mRNA
      encoding VGLUT2. Dual-label immunofluorescent studies followed by confocal laser
      microscopic analysis of the median eminence also demonstrated the occurrence of
      VGLUT2 immunoreactivity within TRH and CRH axon varicosities, suggesting terminal
      glutamate release from these neuroendocrine systems. These data together indicate
      that the hypophysiotropic TRH and CRH neurons possess glutamatergic
      characteristics. Future studies will need to address the physiological
      significance of the endogenous glutamate content in these neurosecretory systems
      in the neuroendocrine regulation of thyroid and adrenal functions.

PMID- 15486234
TI  - From the RSNA refresher courses: a practical approach to the cystic renal mass.
AB  - The pathologic and imaging features of the renal cyst have been well described. A
      fluid-filled lesion is considered a cystic mass (ie, not a simple cyst) when it
      has any of the following features: calcification, high attenuation (>20 HU) at
      computed tomography, signal intensity not typical of water at magnetic resonance
      imaging, septations, multiple locules, enhancement, wall thickening, or
      nodularity. There are two important causes of a cystic renal mass: a complicated
      simple cyst (eg, one with hemorrhage, infection, or ischemia) and cystic renal
      cell carcinoma. At radiologic evaluation of such masses, it is imperative that
      optimal imaging techniques be used. Masses with calcification, high attenuation
      or high signal intensity, or septations can be categorized as benign (no further
      evaluation required), as requiring follow-up (probably benign), or as requiring
      surgery. Lesions requiring surgery can be benign or malignant at microscopic
      examination. Lesions that are multiloculated or demonstrate enhancement, wall
      thickening, or nodularity usually require surgery. When multiple features are
      present (eg, calcification and enhancement), the mass should be managed according
      to its most aggressive feature. Likewise, when there are conflicting findings at
      evaluation with different imaging modalities, the mass should be managed
      according to the most aggressive finding.

PMID- 15486235
TI  - Mimics of renal colic: alternative diagnoses at unenhanced helical CT.
AB  - During the past decade, unenhanced computed tomography (CT) has become the
      standard of reference in the detection of urinary calculi owing to its high
      sensitivity (>95%) and specificity (>98%) in this setting. Numerous diseases may
      manifest as acute flank pain and mimic urolithiasis. Up to one-third of
      unenhanced CT examinations performed because of flank pain may reveal unsuspected
      findings unrelated to stone disease, many of which can help explain the patient's
      condition. Alternative diagnoses are most commonly related to gynecologic
      conditions (especially adnexal masses) and nonstone genitourinary disease (eg,
      pyelonephritis, renal neoplasm), closely followed by gastrointestinal disease
      (especially appendicitis and diverticulitis). Hepatobiliary, vascular, and
      musculoskeletal conditions may also be encountered. Vascular causes of acute
      flank pain must always be considered, since these constitute life-threatening
      emergencies that may require the intravenous administration of contrast material
      for diagnosis. Radiologists must be familiar with the typical findings of urinary
      stone disease at unenhanced CT, as well as the spectrum of alternative diagnoses
      that may be detected with this modality, to accurately diagnose the source of
      flank pain.

PMID- 15486236
TI  - The renal sinus: pathologic spectrum and multimodality imaging approach.
AB  - Various pathologic conditions can occur in the renal sinus, primarily originating
      in the constituents of the renal sinus, and the renal sinus can be secondarily
      involved by surrounding renal parenchymal and adjacent retroperitoneal lesions.
      Lipomatosis and cysts are common renal sinus lesions with little clinical
      significance, but differentiation from other pathologic conditions is important.
      Renal vascular lesions such as renal artery aneurysm or arteriovenous fistula can
      mimic other parapelvic or peripelvic lesions at excretory urography, but their
      vascular nature is evident at color Doppler ultrasonography, contrast material
      enhanced computed tomography (CT), and magnetic resonance (MR) imaging. Although
      most tumors originating in the renal pelvis are transitional cell carcinoma or
      squamous cell carcinoma, renal parenchymal tumors such as renal cell carcinoma or
      benign multilocular cystic nephroma have a tendency to grow into the renal sinus.
      Rare tumors of mesenchymal origin can develop in the renal sinus, but their
      imaging findings are nonspecific. The observation of renal sinus fat is important
      for detecting a small tumor located in that area and determining the exact tumor
      stage. Multiplanar CT or MR images can allow exact evaluation of the extent of
      complex renal sinus disease.

PMID- 15486237
TI  - Recognition of the ovaries and ovarian origin of pelvic masses with CT.
AB  - Knowledge of the morphologic features and ligamentous attachments of the ovaries,
      the relationship of the ovary to the ureter, and the course of the ovarian vein
      and artery is necessary for confident recognition of the ovaries and
      differentiation between ovarian and nonovarian masses with computed tomography
      (CT). The suspensory ligament attaches the ovary to the pelvic sidewall and
      transmits the ovarian vein and artery. This ligament may be seen at CT as a
      linear or fan-shaped soft-tissue band leading to the ovary. The utero-ovarian
      ligament is occasionally visualized with CT as a soft-tissue band between the
      uterus and ovary. The ovaries are usually located anterior or anteromedial to the
      pelvic ureters, whereas iliac lymph nodes are lateral or posterolateral to the
      ureters. Therefore, an ovarian mass displaces the ureter posteriorly or
      posterolaterally, whereas a large lymph node mass displaces the ureter medially
      or anteromedially. An ovarian mass may be draped by ovarian parenchyma, thus
      revealing the origin of the mass. Tracking the ovarian vein from near the level
      of the renal vessels caudally to the pelvis leads to the suspensory ligament
      region and is often helpful in identifying the ovary and differentiating ovarian
      and nonovarian masses.

PMID- 15486238
TI  - Functioning ovarian tumors: direct and indirect findings at MR imaging.
AB  - There are many kinds of ovarian tumors and tumorlike conditions that produce
      estrogen or androgen. Magnetic resonance imaging can demonstrate not only ovarian
      tumors but also an enlarged uterus with a thick endometrium, even in cases of a
      clinically latent excess of estrogen. These clinical and indirect imaging
      findings can aid in the differential diagnosis of ovarian tumors. Granulosa cell
      tumor and thecoma are well-known estrogen-producing tumors. In pediatric or
      postmenopausal patients, they manifest as precocious pseudopuberty or
      postmenopausal bleeding, respectively. Conversely, Sertoli-Leydig cell tumor is
      representative of hormone-producing tumors that cause virilization. However,
      there are other functioning ovarian tumors besides the sex cord-stromal tumors.
      It is well known that metastatic ovarian tumors often have androgen-producing
      stroma and that mucinous cystadenoma sometimes produces estrogens. Most other
      ovarian tumors can produce sexual hormones in their stroma. In addition, some
      endocrinologic abnormalities (eg, polycystic ovary syndrome) also cause
      virilization.

PMID- 15486239
TI  - Pretreatment evaluation of prostate cancer: role of MR imaging and 1H MR
      spectroscopy.
AB  - Magnetic resonance (MR) imaging and hydrogen 1 MR spectroscopy of the prostate
      gland are performed during the same examination with a conventional clinical MR
      unit. Prostate zonal anatomy and prostate cancer are best depicted on multiplanar
      T2-weighted MR images. MR imaging and 1H MR spectroscopy are not used as an
      initial diagnostic tool. Their use in tumor detection is reserved for patients
      with elevated prostate-specific antigen levels in whom previous biopsy results
      were negative. The use of MR imaging and 1H MR spectroscopy for the evaluation of
      tumor location, local extent (extracapsular extension and/or seminal vesicle
      invasion), volume, and aggressiveness is generating strong clinical interest. In
      staging and treatment planning, MR imaging has been shown to have an incremental
      value additive to the value of clinical nomograms. Furthermore, anatomic and
      metabolic mapping of the prostate gland with 1H MR spectroscopy offers the
      possibility of optimizing treatment planning (watchful waiting, surgery, or
      radiation therapy [intensity-modulated radiation therapy or brachytherapy]), thus
      further expanding the role of MR imaging in the achievement of patient-specific,
      individualized treatment.

PMID- 15486240
TI  - Complications of prostate cancer treatment: spectrum of imaging findings.
AB  - The imaging appearances of prostate cancer are well described in the radiology
      literature, but little has been written about the detection and appearance of the
      complications of therapy for this disease. The most frequently used treatments
      for prostate cancer are surgical therapy (eg, radical retropubic prostatectomy,
      radical perineal prostatectomy), radiation therapy (eg, brachytherapy, external
      beam radiation therapy, three-dimensional conformal radiation therapy, intensity
      modulated radiation therapy), and cryoablative therapy, each of which may lead to
      complications with characteristic imaging appearances. Possible complications
      include lymphocele formation; injuries to the ureter, rectum, and urethra;
      prostatic necrosis; vesicourethral anastomotic leak and stricture; urethral
      stricture, necrosis, and fistula; radiation proctitis; transient bladder outlet
      obstruction; radiation-induced urethritis; urinary incontinence; and erectile
      dysfunction. With improvements in surgical techniques and advances in technology,
      complications of therapy for prostate cancer are decreasing but still occur with
      sufficient frequency to warrant familiarity on the part of radiologists.
      Knowledge of the diverse spectrum of these complications and their characteristic
      radiologic features facilitates prompt diagnosis and treatment.

PMID- 15486241
TI  - Imaging of urethral disease: a pictorial review.
AB  - Retrograde urethrography and voiding cystourethrography are the modalities of
      choice for imaging the urethra. Cross-sectional imaging modalities, including
      ultrasonography, magnetic resonance (MR) imaging, and computed tomography, are
      useful for evaluating periurethral structures. Retrograde urethrography is the
      primary imaging modality for evaluating traumatic injuries and inflammatory and
      stricture diseases of the male urethra. Sonourethrography plays an important role
      in the assessment of the thickness and length of bulbar urethral stricture.
      Although voiding cystourethrography is frequently used to evaluate urethral
      diverticula in women, MR imaging is highly sensitive in the demonstration of
      these entities. MR imaging is also accurate in the local staging of urethral
      tumors.

PMID- 15486242
TI  - Fistulas of the lower urinary tract: percutaneous approaches for the management
      of a difficult clinical entity.
AB  - Fistulas of the lower urinary tract are uncommon conditions that may occur
      spontaneously or after therapy in patients with various pelvic abnormalities.
      When present, these fistulas are associated with urine leakage, which is often
      socially distressing and disabling. Unfortunately, factors that lead to the
      formation of genitourinary fistulas often increase their complexity or preclude
      surgical repair. A high failure rate is associated with surgical repair, and many
      patients are not optimal surgical candidates. For such patients, a percutaneous
      treatment approach is highly desirable. Percutaneous ureteral occlusion combined
      with insertion of a functioning nephrostomy tube allows complete diversion of
      urine in those patients in whom nephrostomy alone does not provide adequate
      relief. Many approaches to percutaneous ureteral occlusion have been used with
      variable success, including coils and gelatin sponge, isobutyl-2-cyanoacrylate,
      detachable balloons, radiofrequency electrocautery, ureteral clipping, and solid
      and soft polymer agents. Furthermore, percutaneous or retrograde ureteral stents
      may be used to preserve antegrade urine flow, and surgical options are also
      available. It is essential that the interventional radiologist involved in the
      care of these patients be familiar with these different techniques as well as
      with the limitations, pitfalls, and possible complications of their use.

PMID- 15486243
TI  - Best cases from the AFIP: plexiform neurofibroma of the bladder.

PMID- 15486244
TI  - Epidermoid cyst of the testis: radiologic-pathologic correlation.

PMID- 15486245
TI  - Classic signs in uroradiology.
AB  - The language of radiology is rich with descriptions of imaging findings, often
      metaphorical, which have found common usage in the day-to-day practice of
      genitourinary radiology. These "classic signs" give us confidence in our
      diagnosis. Some of the signs have become so familiar to us that they are referred
      to as an "Aunt Minnie." When the sign is invoked, or an Aunt Minnie is
      recognized, it often brings an impression of the image to mind, and it may have
      specific diagnostic and pathologic implications. The article uses classic signs
      accumulated from the literature to review a variety of pathologic conditions in
      the urinary tract.

PMID- 15486247
TI  - Frequently asked questions: iodinated contrast agents.
AB  - Although iodinated contrast agents are safe and widely used, adverse events occur
      and questions remain about their use, safety, and interactions. Some questions
      are easily answered and others still require extensive investigation. For one
      frequent question--is informed consent necessary before all contrast media
      injections--the simple answer is no. Another question concerns use of contrast
      media in patients with prior reactions or allergies. Contrast agents can be
      safely used in such patients, but special care must be taken to be aware of what
      the previous reaction was and to be ready to treat any reaction. The protective
      role of pre-treatment with steroids is well established for minor reactions, but
      they may not prevent major reactions. It is important to realize that even life
      threatening, anaphylactoid reactions are not the result of a true allergy to
      contrast media. Many questions arise about contrast agent-induced nephropathy.
      Baseline serum creatinine values should be obtained in patients who are at risk,
      not all patients. The incidence and natural history of contrast agent-induced
      nephropathy remain unclear. It occurs only in patients with compromised renal
      function before contrast agent injection, but even patients with normal serum
      creatinine levels can have renal dysfunction. Calculated creatinine clearance is
      a better way to determine risk and to follow this complication. The outcome in
      almost all patients is benign, with progression to end-stage renal disease being
      rare. The major risk factors, in addition to renal dysfunction, are long-standing
      diabetes mellitus, dehydration, and use of other nephrotoxic medications. Recent
      work in preventing and ameliorating contrast agent-induced nephropathy with N
      acetyl cysteine, substitution of an isosmolal nonionic contrast agent, and
      various hydration regimens has been promising. Another common concern is use of
      iodinated contrast agents in pregnant or breast-feeding women. In both cases,
      there is no evidence of harm to the fetus or infant, but it is prudent to weigh
      the theoretical risks and benefits and avoid contrast agent administration unless
      it is truly necessary.

PMID- 15486248
TI  - CT urography.
AB  - With the recent introduction of multi-detector row helical computed tomography
      (CT), the radiologic evaluation of patients with urologic disease has changed
      rapidly. Two major approaches to CT urography have been developed. The first
      approach combines axial CT with timed excretory urography (EU) performed by using
      conventional radiography, digital radiography, or CT scanned projection
      radiography (SPR). This approach produces traditional projection urograms, and
      the timed imaging technique is familiar to radiologists and clinicians.
      Additional excretory phase CT can be performed when the EU findings are positive
      or indeterminate. Improved CT SPR processing technology produces radiographlike
      images, thus eliminating patient transportation between the CT and urography
      suites or the necessity for a CT suite with a ceiling-mounted x-ray tube and a
      modified CT tabletop for performance of EU. The second approach to CT urography
      combines axial CT with thin-section excretory phase CT. The near-isotropic volume
      data set enables creation of high-resolution two- and three-dimensional
      reformatted images. However, the increased amount of radiation and the time
      required for data manipulation are concerns. Further studies evaluating large
      numbers of patients with various urothelial abnormalities will be necessary to
      determine the optimal CT urography technique for clinical practice.

PMID- 15486250
TI  - Imaging-guided radiofrequency ablation of renal masses.
AB  - Substantial and growing evidence indicates that imaging-guided percutaneous
      radiofrequency ablation of small renal cell carcinomas (RCCs) is effective for
      complete tumor eradication. The rate of successful radiofrequency treatment of
      small RCCs ranges from 79% to 97%, with a 1% rate of serious complications. For
      patients who are considered high-risk candidates for nephrectomy, percutaneous
      radiofrequency ablation represents another treatment option. The article
      summarizes the published results for this technique and also describes the
      indications, techniques, procedural risks, and applications for percutaneous
      radiofrequency ablation of RCCs. The successful use of radiofrequency ablation
      for treatment of recurrent and metastatic RCCs is also described.

PMID- 15486251
TI  - Adrenal masses: mr imaging features with pathologic correlation.
AB  - The detection of adrenal lesions has increased with the expanding use of cross
      sectional imaging. Magnetic resonance (MR) imaging is often useful for
      characterizing adrenal masses. Adrenal masses can be classified into various
      groups on the basis of the presence of intracellular lipid, macroscopic fat,
      hemorrhage, and cystic changes and the vascularity and shape of the tumor. These
      imaging features can be used by the radiologist to suggest or confirm a diagnosis
      for most adrenal masses, including adenoma, hyperplasia, simple and complicated
      cysts, lymphangioma, myelolipoma, pheochromocytoma, hemorrhage, cortical
      carcinoma, neuroblastoma, lymphoma, and metastases. Adenomas and metastases are
      common, and a decrease in signal intensity on out-of-phase images can be used to
      differentiate between them. Carcinoma is a possible diagnosis if that decrease in
      signal intensity is heterogeneous. Benign disease is diagnosed if macroscopic fat
      or a homogeneous cystlike lesion is seen. Recognition of the typical MR imaging
      features is important because it often changes the treatment approach and may
      obviate surgery.

PMID- 15486252
TI  - Pheochromocytoma: an imaging chameleon.
AB  - Pheochromocytomas are rare catecholamine-secreting tumors with many clinical and
      imaging manifestations. They may produce overwhelming cardiovascular crises if
      the diagnosis is not made or if appropriate treatment is delayed. It is thus
      important to recognize both their characteristic and atypical imaging
      appearances. Pheochromocytomas are encountered, sometimes unexpectedly, across a
      range of imaging modalities. They are characteristically solid, hypervascular
      masses with high signal intensity on T2-weighted magnetic resonance (MR) images.
      A wide spectrum of imaging appearances is seen, however, and pheochromocytomas
      may mimic other adrenal lesions, both benign and malignant. They may be dark on
      T2-weighted MR images, in contrast to their more classic bright T2-weighted
      appearance. Other atypical features include fatty, hemorrhagic, cystic, and
      calcific changes. Pheochromocytomas may contain sufficient fat to be mistaken for
      an adenoma at computed tomography (CT) or MR imaging. They may also demonstrate
      rapid contrast material washout and be mistaken for an adenoma owing to their
      deenhancement profile; however, their washout pattern can be inconsistent. The
      appearance of pheochromocytomas at radionuclide imaging is also unpredictable.
      These characteristics at CT, MR imaging, and scintigraphy pose diagnostic
      challenges, since they allow pheochromocytomas to mimic many other adrenal
      masses. Pheochromocytoma is an important, often clinically occult neoplasm with
      devastating consequences if overlooked. Radiologists must be aware of the various
      forms that pheochromocytomas can assume at imaging.

PMID- 15486253
TI  - Geochemical precursors to volcanic activity at Mount St. Helens, USA.
AB  - The importance of the interplay between degassing and crystallization before and
      after the eruption of Mount St. Helens (Washington, USA) in 1980 is well
      established. Here, we show that degassing occurred over a period of decades to
      days before eruptions and that the manner of degassing, as deduced from
      geochemical signatures within the magma, was characteristic of the eruptive
      style. Trace element (lithium) and short-lived radioactive isotope (lead-210 and
      radium-226) data show that ascending magma stalled within the conduit, leading to
      the accumulation of volatiles and the formation of lead-210 excesses, which
      signals the presence of degassing magma at depth.

PMID- 15486254
TI  - Status and trends of amphibian declines and extinctions worldwide.
AB  - The first global assessment of amphibians provides new context for the well
      publicized phenomenon of amphibian declines. Amphibians are more threatened and
      are declining more rapidly than either birds or mammals. Although many declines
      are due to habitat loss and overutilization, other, unidentified processes
      threaten 48% of rapidly declining species and are driving species most quickly to
      extinction. Declines are nonrandom in terms of species' ecological preferences,
      geographic ranges, and taxonomic associations and are most prevalent among
      Neotropical montane, stream-associated species. The lack of conservation remedies
      for these poorly understood declines means that hundreds of amphibian species now
      face extinction.

PMID- 15486255
TI  - Hysteretic adsorption and desorption of hydrogen by nanoporous metal-organic
      frameworks.
AB  - Adsorption and desorption of hydrogen from nanoporous materials, such as
      activated carbon, is usually fully reversible. We have prepared nanoporous metal
      organic framework materials with flexible linkers in which the pore openings, as
      characterized in the static structures, appear to be too small to allow H2 to
      pass. We observe hysteresis in their adsorption and desorption kinetics above the
      supercritical temperature of H2 that reflects the dynamical opening of the
      "windows" between pores. This behavior would allow H2 to be adsorbed at high
      pressures but stored at lower pressures.

PMID- 15486256
TI  - The 1.2-megabase genome sequence of Mimivirus.
AB  - We recently reported the discovery and preliminary characterization of Mimivirus,
      the largest known virus, with a 400-nanometer particle size comparable to
      mycoplasma. Mimivirus is a double-stranded DNA virus growing in amoebae. We now
      present its 1,181,404-base pair genome sequence, consisting of 1262 putative open
      reading frames, 10% of which exhibit a similarity to proteins of known functions.
      In addition to exceptional genome size, Mimivirus exhibits many features that
      distinguish it from other nucleocytoplasmic large DNA viruses. The most
      unexpected is the presence of numerous genes encoding central protein-translation
      components, including four amino-acyl transfer RNA synthetases, peptide release
      factor 1, translation elongation factor EF-TU, and translation initiation factor
      1. The genome also exhibits six tRNAs. Other notable features include the
      presence of both type I and type II topoisomerases, components of all DNA repair
      pathways, many polysaccharide synthesis enzymes, and one intein-containing gene.
      The size and complexity of the Mimivirus genome challenge the established
      frontier between viruses and parasitic cellular organisms. This new sequence data
      might help shed a new light on the origin of DNA viruses and their role in the
      early evolution of eukaryotes.

PMID- 15486257
TI  - Neuroscience and neuroethics.

PMID- 15486258
TI  - Drug safety. Withdrawal of Vioxx casts a shadow over COX-2 inhibitors.

PMID- 15486259
TI  - Influenza. Crisis underscores fragility of vaccine production system.

PMID- 15486261
TI  - Chemistry. Mass spectrometrists salivate over recipe for ions alfresco.

PMID- 15486260
TI  - Medicine. Microbicide shuts the door on HIV.

PMID- 15486262
TI  - Graduate education. Hughes, NIH team up on novel training program.

PMID- 15486263
TI  - Genetics. Disease backs cancer origin theory.

PMID- 15486264
TI  - Ecology. Global survey documents puzzling decline of amphibians.

PMID- 15486265
TI  - Nobel Peace Prize. Kenya's Maathai wins for reforestation work.

PMID- 15486266
TI  - Influenza: girding for disaster. Looking the pandemic in the eye.

PMID- 15486267
TI  - Influenza: girding for disaster. Facing down pandemic flu, the world's defenses
      are weak.

PMID- 15486268
TI  - Influenza: girding for disaster. Searching for all-powerful flu weapons.

PMID- 15486269
TI  - Influenza: girding for disaster. Vaccinating birds may help to curtail virus's
      spread.

PMID- 15486270
TI  - Influenza: girding for disaster. Asia struggles to keep humans and chickens
      apart.

PMID- 15486271
TI  - Nobel Prizes. Laurels to three who tamed equations of quark theory.

PMID- 15486273
TI  - Nobel Prizes. Macroeconomists showed why good intentions go wrong.

PMID- 15486272
TI  - Nobel Prizes. Gold medal from cellular trash.

PMID- 15486274
TI  - Ongoing controversy over Romanov remains.

PMID- 15486275
TI  - Producing neuronal energy.

PMID- 15486276
TI  - Comment on "Force-clamp spectroscopy monitors the folding trajectory of a single
      protein".

PMID- 15486278
TI  - Climate. To hedge or not against an uncertain climate future?

PMID- 15486279
TI  - Materials science. Some Assembly Required.

PMID- 15486280
TI  - Ecology and conservation. Space--the final frontier for economists and elephants.

PMID- 15486281
TI  - Behavior. A marketplace in the brain?

PMID- 15486282
TI  - Physics. The environment matters--even on the atomic scale.

PMID- 15486283
TI  - Biomedicine. Insulin resistance takes a trip through the ER.

PMID- 15486284
TI  - Eppendorf essay winner. Deconstructing C. elegans sensory mechanotransduction.

PMID- 15486287
TI  - Behavioral neuroscience uncaged.

PMID- 15486288
TI  - Cognitive memory: cellular and network machineries and their top-down control.
AB  - A brain-wide distributed network orchestrates cognitive memorizing and
      remembering of explicit memory (i.e., memory of facts and events). The network
      was initially identified in humans and is being systematically investigated in
      molecular/genetic, single-unit, lesion, and imaging studies in animals. The types
      of memory identified in humans are extended into animals as episodic-like (event)
      memory or semantic-like (fact) memory. The unique configurational association
      between environmental stimuli and behavioral context, which is likely the basis
      of episodic-like memory, depends on neural circuits in the medial temporal lobe,
      whereas memory traces representing repeated associations, which is likely the
      basis of semantic-like memory, are consolidated in the domain-specific regions in
      the temporal cortex. These regions are reactivated during remembering and
      contribute to the contents of a memory. Two types of retrieval signal reach the
      cortical representations. One runs from the frontal cortex for active (or
      effortful) retrieval (top-down signal), and the other spreads backward from the
      medial temporal lobe for automatic retrieval. By sending the top-down signal to
      the temporal cortex, frontal regions manipulate and organize to-be-remembered
      information, devise strategies for retrieval, and also monitor the outcome, with
      dissociated frontal regions making functionally separate contributions. The
      challenge is to understand the hierarchical interactions between these multiple
      cortical areas, not only with a correlational analysis but also with an
      interventional study demonstrating the causal necessity and the direction of the
      causality.

PMID- 15486289
TI  - Language and the origin of numerical concepts.
AB  - Reports of research with the Piraha and Munduruku Amazonian Indians of Brazil
      lend themselves to discussions of the role of language in the origin of numerical
      concepts. The research findings indicate that, whether or not humans have an
      extensive counting list, they share with nonverbal animals a language-independent
      representation of number, with limited, scale-invariant precision. What causal
      role, then, does knowledge of the language of counting serve? We consider the
      strong Whorfian proposal, that of linguistic determinism; the weak Whorfian
      hypothesis, that language influences how we think; and that the "language of
      thought" maps to spoken language or symbol systems.

PMID- 15486290
TI  - The role of the medial frontal cortex in cognitive control.
AB  - Adaptive goal-directed behavior involves monitoring of ongoing actions and
      performance outcomes, and subsequent adjustments of behavior and learning. We
      evaluate new findings in cognitive neuroscience concerning cortical interactions
      that subserve the recruitment and implementation of such cognitive control. A
      review of primate and human studies, along with a meta-analysis of the human
      functional neuroimaging literature, suggest that the detection of unfavorable
      outcomes, response errors, response conflict, and decision uncertainty elicits
      largely overlapping clusters of activation foci in an extensive part of the
      posterior medial frontal cortex (pMFC). A direct link is delineated between
      activity in this area and subsequent adjustments in performance. Emerging
      evidence points to functional interactions between the pMFC and the lateral
      prefrontal cortex (LPFC), so that monitoring-related pMFC activity serves as a
      signal that engages regulatory processes in the LPFC to implement performance
      adjustments.

PMID- 15486291
TI  - Neuroeconomics: the consilience of brain and decision.
AB  - Economics, psychology, and neuroscience are converging today into a single,
      unified discipline with the ultimate aim of providing a single, general theory of
      human behavior. This is the emerging field of neuroeconomics in which
      consilience, the accordance of two or more inductions drawn from different groups
      of phenomena, seems to be operating. Economists and psychologists are providing
      rich conceptual tools for understanding and modeling behavior, while
      neurobiologists provide tools for the study of mechanism. The goal of this
      discipline is thus to understand the processes that connect sensation and action
      by revealing the neurobiological mechanisms by which decisions are made. This
      review describes recent developments in neuroeconomics from both behavioral and
      biological perspectives.

PMID- 15486292
TI  - arrA is a reliable marker for As(V) respiration.
AB  - Arsenate [As(V)]-respiring bacteria affect the speciation and mobilization of
      arsenic in the environment. This can lead to arsenic contamination of drinking
      water supplies and deleterious consequences for human health. Using molecular
      genetics, we show that the functional gene for As(V) respiration, arrA, is highly
      conserved; that it is required for As(V) reduction to arsenite when arsenic is
      sorbed onto iron minerals; and that it can be used to identify the presence and
      activity of As(V)-respiring bacteria in arsenic-contaminated iron-rich sediments.
      The expression of arrA thus can be used to monitor sites in which As(V)-respiring
      bacteria may be controlling arsenic geochemistry.

PMID- 15486293
TI  - Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes.
AB  - Obesity contributes to the development of type 2 diabetes, but the underlying
      mechanisms are poorly understood. Using cell culture and mouse models, we show
      that obesity causes endoplasmic reticulum (ER) stress. This stress in turn leads
      to suppression of insulin receptor signaling through hyperactivation of c-Jun N
      terminal kinase (JNK) and subsequent serine phosphorylation of insulin receptor
      substrate-1 (IRS-1). Mice deficient in X-box-binding protein-1 (XBP-1), a
      transcription factor that modulates the ER stress response, develop insulin
      resistance. These findings demonstrate that ER stress is a central feature of
      peripheral insulin resistance and type 2 diabetes at the molecular, cellular, and
      organismal levels. Pharmacologic manipulation of this pathway may offer novel
      opportunities for treating these common diseases.

PMID- 15486294
TI  - A Bayesian truth serum for subjective data.
AB  - Subjective judgments, an essential information source for science and policy, are
      problematic because there are no public criteria for assessing judgmental
      truthfulness. I present a scoring method for eliciting truthful subjective data
      in situations where objective truth is unknowable. The method assigns high scores
      not to the most common answers but to the answers that are more common than
      collectively predicted, with predictions drawn from the same population. This
      simple adjustment in the scoring criterion removes all bias in favor of
      consensus: Truthful answers maximize expected score even for respondents who
      believe that their answer represents a minority view.

PMID- 15486295
TI  - Stable low-pressure hydrogen clusters stored in a binary clathrate hydrate.
AB  - Thermodynamic, x-ray diffraction, and Raman and nuclear magnetic resonance
      spectroscopy measurements show that clusters of H2 can be stabilized and stored
      at low pressures in a sII binary clathrate hydrate. Clusters of H2 molecules
      occupy small water cages, whereas large water cages are singly occupied by
      tetrahydrofuran. The presence of this second guest component stabilizes the
      clathrate at pressures of 5 megapascals at 279.6 kelvin, versus 300 megapascals
      at 280 kelvin for pure H2 hydrate.

PMID- 15486296
TI  - Mass spectrometry sampling under ambient conditions with desorption electrospray
      ionization.
AB  - A new method of desorption ionization is described and applied to the ionization
      of various compounds, including peptides and proteins present on metal, polymer,
      and mineral surfaces. Desorption electrospray ionization (DESI) is carried out by
      directing electrosprayed charged droplets and ions of solvent onto the surface to
      be analyzed. The impact of the charged particles on the surface produces gaseous
      ions of material originally present on the surface. The resulting mass spectra
      are similar to normal ESI mass spectra in that they show mainly singly or
      multiply charged molecular ions of the analytes. The DESI phenomenon was observed
      both in the case of conductive and insulator surfaces and for compounds ranging
      from nonpolar small molecules such as lycopene, the alkaloid coniceine, and small
      drugs, through polar compounds such as peptides and proteins. Changes in the
      solution that is sprayed can be used to selectively ionize particular compounds,
      including those in biological matrices. In vivo analysis is demonstrated.

PMID- 15486297
TI  - A network of superconducting gravimeters detects submicrogal coseismic gravity
      changes.
AB  - With high-resolution continuous gravity recordings from a regional network of
      superconducting gravimeters, we have detected permanent changes in gravity
      acceleration associated with a recent large earthquake. Detected changes in
      gravity acceleration are smaller than 10(-8) meters seconds(-2) (1 micro-Galileo,
      about 10(-9) times the surface gravity acceleration) and agree with theoretical
      values calculated from a dislocation model. Superconducting gravimetry can
      contribute to the studies of secular gravity changes associated with tectonic
      processes.

PMID- 15486298
TI  - Local endemism within the Western Ghats-sri Lanka biodiversity hotspot.
AB  - The apparent biotic affinities between the mainland and the island in the Western
      Ghats-Sri Lanka biodiversity hotspot have been interpreted as the result of
      frequent migrations during recent periods of low sea level. We show, using
      molecular phylogenies of two invertebrate and four vertebrate groups, that biotic
      interchange between these areas has been much more limited than hitherto assumed.
      Despite several extended periods of land connection during the past 500,000
      years, Sri Lanka has maintained a fauna that is largely distinct from that of the
      Indian mainland. Future conservation programs for the subcontinent should take
      into account such patterns of local endemism at the finest scale at which they
      may occur.

PMID- 15486299
TI  - Regulation of gene expression by a metabolic enzyme.
AB  - Gene expression in eukaryotes is normally believed to be controlled by
      transcriptional regulators that activate genes encoding structural proteins and
      enzymes. To identify previously unrecognized DNA binding activities, a yeast
      proteome microarray was screened with DNA probes; Arg5,6, a well-characterized
      mitochondrial enzyme involved in arginine biosynthesis, was identified. Chromatin
      immunoprecipitation experiments revealed that Arg5,6 is associated with specific
      nuclear and mitochondrial loci in vivo, and Arg5,6 binds to specific fragments in
      vitro. Deletion of Arg5,6 causes altered transcript levels of both nuclear and
      mitochondrial target genes. These results indicate that metabolic enzymes can
      directly regulate eukaryotic gene expression.

PMID- 15486300
TI  - Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of
      CCR5.
AB  - Topical agents, such as microbicides, that can protect against human
      immunodeficiency virus (HIV) transmission are urgently needed. Using a chimeric
      simian/human immunodeficiency virus (SHIV SF162), which is tropic for the
      chemokine receptor CCR5, we report that topical application of high doses of PSC
      RANTES, an amino terminus-modified analog of the chemokine RANTES, provided
      potent protection against vaginal challenge in rhesus macaques. These
      experimental findings have potentially important implications for understanding
      vaginal transmission of HIV and the design of strategies for its prevention.

PMID- 15486301
TI  - Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal
      plasticity.
AB  - Long-term memory is thought to be mediated by protein synthesis-dependent, late
      phase long-term potentiation (L-LTP). Two secretory proteins, tissue plasminogen
      activator (tPA) and brain-derived neurotrophic factor (BDNF), have been
      implicated in this process, but their relationship is unclear. Here we report
      that tPA, by activating the extracellular protease plasmin, converts the
      precursor proBDNF to the mature BDNF (mBDNF), and that such conversion is
      critical for L-LTP expression in mouse hippocampus. Moreover, application of
      mBDNF is sufficient to rescue L-LTP when protein synthesis is inhibited, which
      suggests that mBDNF is a key protein synthesis product for L-LTP expression.

PMID- 15486302
TI  - Molecular architecture of the KvAP voltage-dependent K+ channel in a lipid
      bilayer.
AB  - We have analyzed the local structure and dynamics of the prokaryotic voltage
      dependent K+ channel (KvAP) at 0 millivolts, using site-directed spin labeling
      and electron paramagnetic resonance spectroscopy. We show that the S4 segment is
      located at the protein/lipid interface, with most of its charges protected from
      the lipid environment. Structurally, S4 is highly dynamic and is separated into
      two short helices by a flexible linker. Accessibility and dynamics data indicate
      that the S1 segment is surrounded by other parts of the protein. We propose that
      S1 is at the contact interface between the voltage-sensing and pore domains.
      These results establish the general principles of voltage-dependent channel
      structure in a biological membrane.

PMID- 15486303
TI  - Exact and approximate arithmetic in an Amazonian indigene group.
AB  - Is calculation possible without language? Or is the human ability for arithmetic
      dependent on the language faculty? To clarify the relation between language and
      arithmetic, we studied numerical cognition in speakers of Munduruku, an Amazonian
      language with a very small lexicon of number words. Although the Munduruku lack
      words for numbers beyond 5, they are able to compare and add large approximate
      numbers that are far beyond their naming range. However, they fail in exact
      arithmetic with numbers larger than 4 or 5. Our results imply a distinction
      between a nonverbal system of number approximation and a language-based counting
      system for exact number and arithmetic.

PMID- 15486304
TI  - Separate neural systems value immediate and delayed monetary rewards.
AB  - When humans are offered the choice between rewards available at different points
      in time, the relative values of the options are discounted according to their
      expected delays until delivery. Using functional magnetic resonance imaging, we
      examined the neural correlates of time discounting while subjects made a series
      of choices between monetary reward options that varied by delay to delivery. We
      demonstrate that two separate systems are involved in such decisions. Parts of
      the limbic system associated with the midbrain dopamine system, including
      paralimbic cortex, are preferentially activated by decisions involving
      immediately available rewards. In contrast, regions of the lateral prefrontal
      cortex and posterior parietal cortex are engaged uniformly by intertemporal
      choices irrespective of delay. Furthermore, the relative engagement of the two
      systems is directly associated with subjects' choices, with greater relative
      fronto-parietal activity when subjects choose longer term options.

PMID- 15486305
TI  - Stem cell transplantation reveals that absence of macrophage CD36 is protective
      against atherosclerosis.
AB  - OBJECTIVE: CD36 is expressed on multiple cell types and has numerous functions, a
      subset of which can impact on atherogenesis. In previous work, we demonstrated
      that CD36 absence was protective against lesion formation. The current objective
      was to determine whether absence of macrophage CD36 alone was protective. METHODS
      AND RESULTS: Lethal irradiation and stem cell transfer were used to create
      chimeric mice that did or did not express macrophage CD36 in the context of the
      Apo E-null model of atherosclerosis. After engraftment, mice were fed a Western
      diet for 12 weeks. White cell counts, plasma levels of lipoproteins,
      triacylglycerol, and nonesterified fatty acids were determined, and glucose
      tolerance tests were preformed. Lesion area was assessed quantitatively after oil
      red O staining. Mice lacking CD36 in macrophages alone were profoundly protected
      against atherosclerosis (88.1% reduction of lesion area throughout the aortic
      tree). Re-introduction of macrophage CD36 resulted in a 2.11-fold increase in
      lesion area. There were no differences in engraftment, macrophage recruitment,
      glucose tolerance, weight, and total, low-density lipoprotein, and high-density
      lipoprotein cholesterol among the groups. Lesions contained similar percent
      macrophage antigen-positive area. CONCLUSIONS: Protection in this model is
      primarily caused by loss of CD36 macrophage function.

PMID- 15486306
TI  - Inhibitory effect of high concentration of glucose on relaxations to activation
      of ATP-sensitive K+ channels in human omental artery.
AB  - OBJECTIVE: The present study was designed to examine in the human omental artery
      whether high concentrations of D-glucose inhibit the activity of ATP-sensitive K+
      channels in the vascular smooth muscle and whether this inhibitory effect is
      mediated by the production of superoxide. METHODS AND RESULTS: Human omental
      arteries without endothelium were suspended for isometric force recording.
      Changes in membrane potentials were recorded and production of superoxide was
      evaluated. Glibenclamide abolished vasorelaxation and hyperpolarization in
      response to levcromakalim. D-glucose (10 to 20 mmol/L) but not l-glucose (20
      mmol/L) reduced these vasorelaxation and hyperpolarization. Tiron and
      diphenyleneiodonium, but not catalase, restored vasorelaxation and
      hyperpolarization in response to levcromakalim in arteries treated with D
      glucose. Calphostin C and Go6976 simultaneously recovered these vasorelaxation
      and hyperpolarization in arteries treated with D-glucose. Phorbol 12-myristate 13
      acetate (PMA) inhibited the vasorelaxation and hyperpolarization, which are
      recovered by calphostin C as well as Go6976. D-glucose and PMA, but not l
      glucose, significantly increased superoxide production from the arteries, whereas
      such increased production was reversed by Tiron. CONCLUSIONS: These results
      suggest that in the human visceral artery, acute hyperglycemia modulates
      vasodilation mediated by ATP-sensitive K+ channels via the production of
      superoxide possibly mediated by the activation of protein kinase C.

PMID- 15486307
TI  - Cardiovascular risk in type 2 diabetes is associated with variation at the PPARG
      locus: a Go-DARTS study.
AB  - OBJECTIVE: The Pro12Ala polymorphism of PPARG modulates risk of developing type 2
      diabetes. The Ala allele has also been associated with a reduced risk of
      cardiovascular events. We have shown previously that the linked T allele of the
      C1431T polymorphism influences Ala12-associated diabetes risk and that the 2
      polymorphisms have opposing associations with body weight. We therefore
      investigated the association of these 2 variants with cardiovascular events in
      people with type 2 diabetes. METHODS AND RESULTS: We performed a cohort study of
      2016 individuals and used Cox proportional hazards to analyze risk of myocardial
      infarction or death by PPARG Pro12Ala and C1431T genotypes, adjusting for age,
      sex, and smoking status. In individuals enrolled <70 years of age, the hazard for
      a first nonfatal event associated with the Ala12 allele was 0.21 (CI, 0.06 to
      0.69; P=0.01) and the T1431 allele 9.9 (CI, 1.90 to 51.29; P=0.007). These
      opposing associations remained significant after correction for other
      conventional risk factors. The T1431 allele was also associated with all-cause
      mortality. CONCLUSIONS: This study confirms the association of the Ala12 allele
      with reduced risk of myocardial infarction in a type 2 diabetic population and
      demonstrates that the T allele independently associates with an increased risk.

PMID- 15486308
TI  - Transcription factor sterol regulatory element binding protein 2 regulates
      scavenger receptor Cla-1 gene expression.
AB  - OBJECTIVE: The human scavenger receptor class B type I (Cla-1) plays a key role
      in cellular cholesterol movement in facilitating transport of cholesterol between
      cells and lipoproteins. Indirect evidence has suggested that Cla-1 gene
      expression is under the feedback control of cellular cholesterol content. To
      define the molecular mechanisms underlying such putative regulation, we evaluated
      whether Cla-1 is a target gene of the sterol regulatory element binding protein
      (SREBP) transcription factor family. METHODS AND RESULTS: Transient transfections
      demonstrated that SREBP factors induce Cla-1 promoter activity and that SREBP-2
      is a more potent inducer than the SREBP-1a isoform. The 5'-deletion analysis of 3
      kb of the 5'-flanking sequence of the Cla-1 gene, combined with site-directed
      mutagenesis and electrophoretic mobility shift assay, allowed identification of a
      unique sterol responsive element. SREBP-mediated Cla-1 regulation was confirmed
      in stably transfected human embryonic kidney 293 cells expressing the active form
      of SREBP-2 at incremental levels. In these cell lines, Cla-1 mRNA and protein
      levels were increased in direct proportion to the level of SREBP-2 expression.
      CONCLUSIONS: These findings provide evidence that SREBP-2, a key regulator of
      cellular cholesterol uptake through modulation of the expression of the low
      density lipoprotein receptor gene, may influence cellular cholesterol homeostasis
      via regulation of Cla-1 gene expression.

PMID- 15486309
TI  - Induction of angiogenesis by heat shock protein 90 mediated by protein kinase Akt
      and endothelial nitric oxide synthase.
AB  - OBJECTIVE: A specific inhibitor of heat shock protein 90 (Hsp90), 17-AAG, has
      been shown to inhibit tumor growth through cell cycle arrest, differentiation, or
      apoptosis. Because angiogenesis is important for tumor growth, we hypothesize
      that inhibition of angiogenesis by 17-AAG may mediate some of its antitumor
      effects. METHODS AND RESULTS: Because protein kinase Akt and endothelial nitric
      oxide synthase (eNOS) are critical for angiogenesis, we studied the effects of 17
      AAG on the phosphorylation and expression of Akt and eNOS in human umbilical vein
      endothelial cells. In a concentration- and time-dependent manner, inhibition of
      Hsp90 by 17-AAG decreased Akt and eNOS expression by 74% and 81%, respectively.
      Inhibition of eNOS expression by 17-AAG occurred at the transcriptional level as
      determined by eNOS promoter activity and nuclear run-on assay. Furthermore,
      treatment with 17-AAG decreased basal and vascular endothelial growth factor
      stimulated Akt and eNOS phosphorylation. This corresponded with decreased NO
      production and inhibition of endothelial cell migration and angiogenesis. The
      anti-angiogenic effect of 17-AAG was partially reversed by the NO donor, SNAP.
      CONCLUSIONS: These findings indicate that Hsp90 is important not only for Akt and
      eNOS phosphorylation but also for eNOS gene transcription and suggests that Hsp90
      may be a novel target for anti-angiogenic therapy.

PMID- 15486310
TI  - Increased vascular wall thrombogenicity combined with reduced blood flow promotes
      occlusive thrombus formation in rabbit femoral artery.
AB  - OBJECTIVE: Plaque disruption does not always result in complete thrombotic
      occlusion. The mechanism of arterial thrombus propagation remains unclear.
      METHODS AND RESULTS: We studied how vascular wall thrombogenicity and blood flow
      reduction affect thrombus propagation using a rabbit model of single and repeated
      balloon injury. After balloon injury of the normal femoral artery, the blood flow
      was reduced to 50%, 25%, or 10% (n=5). Small mural thrombi composed of aggregated
      platelets were produced, but no occlusive thrombi developed in any flow
      reduction. Three weeks after the first balloon injury, neointima with tissue
      factor expression and increased procoagulant activity was developed. Balloon
      injury of the neointima with the same blood flow reduction (n=5) induced fibrin
      rich thrombus formation. Additionally, injury with flow reduced to 25% and 10%
      promoted thrombus propagation resulting in vessel occlusion within 160+/-18 and
      71+/-17 seconds, respectively. An injection of anti-von Willebrand factor (vWF)
      monoclonal antibody (AJW200; 1.0 mg/kg) prevented occlusive thrombus formation.
      CONCLUSIONS: Increased vascular wall thrombogenicity together with a substantial
      blood flow reduction is crucial for occlusive thrombus formation, and vWF plays
      an important role in thrombus propagation. Reduced blood flow at plaque
      disruption sites might contribute to thrombus propagation leading to acute
      coronary syndromes.

PMID- 15486311
TI  - Vein graft neointimal hyperplasia is exacerbated by tumor necrosis factor
      receptor-1 signaling in graft-intrinsic cells.
AB  - OBJECTIVE: Vein graft remodeling and neointimal hyperplasia involve inflammation,
      graft-intrinsic cells, and recruitment of vascular progenitor cells. We sought to
      examine if the inflammatory cytokine tumor necrosis factor (TNF) affects vein
      graft remodeling via its p55 TNF receptor-1 (p55). METHODS AND RESULTS: Inferior
      vena cava-to-carotid artery interposition grafting was performed between p55-/-
      and congenic (C57Bl/6) wild-type (WT) mice. Immunofluorescence revealed TNF in
      early (2-week) vein grafts. Six weeks postoperatively, luminal and medial areas
      were indistinguishable among all vein graft groups. However, neointimal area was
      reduced in p55-/- grafts: by 40% in p55-/- grafts placed in p55-/- recipients,
      and by 21% in p55-/- grafts placed in WT recipients, compared with WT grafts in
      WT recipients (P<0.05). In 2-week-old vein grafts, p55 deficiency reduced
      intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and
      monocyte chemoattractant protein-1 expression by 50% to 60%, and increased the
      extent of graft endothelialization. In vitro, TNF promoted chemokine expression
      and [3H]thymidine incorporation in vascular smooth muscle cells (SMCs) from WT,
      but not from p55-/- mice. However, responses of WT and p55-/- SMCs to other
      growth factors were equivalent. CONCLUSIONS: Signaling via p55, in vein graft
      intrinsic cells, contributes to the pathogenesis of vein graft neointimal
      hyperplasia.

PMID- 15486312
TI  - Molecular evaluation of endothelial progenitor cells in patients with ischemic
      limbs: therapeutic effect by stem cell transplantation.
AB  - OBJECTIVE: Although some patients with limb ischemia have recently undergone
      therapeutic angiogenesis by cell transplantation, their angiogenic potential has
      not been well characterized. It is also important to evaluate endothelial
      progenitor cell (EPC) contents in different stem cell sources to choose the best
      material for therapeutic angiogenesis. METHODS AND RESULTS: We quantitated the
      mRNA expression of EPC-specific molecules (eg, Flk-1, Flt-1, CD133, VE-cadherin,
      etc) in bone marrow-derived or peripheral blood-derived mononuclear cells
      obtained from patients with ischemic limbs, using real-time reverse-transcription
      polymerase chain reaction technique. The mRNA expression level of EPC markers was
      significantly lower in the patients than in healthy controls, which was
      consistent with results of flow cytometric analysis. However, the implantation of
      autologous bone marrow mononuclear cells increased the circulating EPCs in the
      peripheral blood of patients. We furthermore revealed the different expression
      pattern of EPC markers in possible sources for stem cell transplantation,
      including normal bone marrow, peripheral blood obtained from recombinant
      granulocyte colony-stimulating factor-treated donor, and umbilical cord blood.
      CONCLUSIONS: Patients with peripheral obstructive arterial diseases may have
      lower angiogenic potential because of decreased expression of EPC specific
      molecules in their marrow and blood. Therapeutic angiogenesis by transplantation
      of autologous marrow mononuclear cells increased circulating EPCs in the patients
      and improved ischemic symptoms.

PMID- 15486313
TI  - Low-grade inflammation and microalbuminuria in hypertension.
AB  - Background- Albuminuria and C-reactive protein (CRP), a marker of systemic low
      grade inflammation, are frequently elevated in essential hypertension and predict
      cardiovascular prognosis independent of conventional risk factors. However, in
      spite of their potentially important links, the interrelationships between the 2
      parameters have not been explored in depth in hypertensive patients. METHODS AND
      RESULTS: Albuminuria (the mean of 3 overnight urine collections), high-sensitive
      CRP (hs-CRP), 24-hour blood pressure (BP), weight, lipids, poststimulative (75 g
      PO) plasma glucose, insulin, and insulin sensitivity by the homeostasis model
      assessment model were evaluated in 220 never treated, nondiabetic, uncomplicated
      essential hypertensive men. Albuminuria > or =15 microg/min was defined as
      microalbuminuria and hs-CRP values above and below median (2.3 mg/L) as high and
      low, respectively. Concentric left ventricular hypertrophy was diagnosed by
      echocardiography, and a full-blown metabolic syndrome was identified in presence
      of hypertension and at least 3 of following: obesity, subclinical hyperglycemia,
      low high-density lipoprotein (HDL) and high triglycerides. Microalbuminuria was
      present in 54 patients, 29 with high hs-CRP characterized by higher 24-hour
      systolic BP, postload glucose, body mass index, lower HDL cholesterol, more
      frequent metabolic syndrome, concentric LVH, and active smoking than those with
      either isolated microalbuminuria (n=27) or normoalbuminuria. CONCLUSIONS:
      Microalbuminuria accompanied by evidence of subclinical inflammation is a strong
      correlate of metabolic abnormalities in essential hypertension and identifies a
      patient subset at very high cardiovascular risk. In contrast, isolated
      microalbuminuria may represent a distinct pathophysiological condition
      characterized by a more benign profile and possibly a better prognosis.

PMID- 15486314
TI  - Ultrasensitive confocal fluorescence microscopy of C-reactive protein interacting
      with FcgammaRIIa.
AB  - BACKGROUND: C-Reactive protein (CRP) is an acute phase protein with a suggested
      pathogenic role in cardiovascular disease. Previous reports proposed that the low
      affinity IgG receptor FcgammaRIIa is the major receptor for CRP. However, these
      reports were met with criticism because the use of anti-CRP antibodies in the
      detection of CRP binding to FcgammaRIIa may have caused false-positive results.
      METHODS AND RESULTS: To resolve this controversy, we used ultrasensitive
      fluorescence microscopy to study the association, dissociation, and equilibrium
      of CRP binding to FcgammaRIIa. CRP indeed binds to FcgammaRIIa, with low
      association rates and dissociation rates. Anti-CRP antibodies markedly enhance
      binding, as is evident from the decrease of the equilibrium dissociation
      coefficient by 2 orders of magnitude. CONCLUSIONS: Our study demonstrates the
      virtues of single fluorophore labeling and highlights the pitfalls of
      immunolabeling in investigating CRP/Fc receptor interactions. Importantly, this
      article provides the first quantitative characterization of CRP binding to
      FcgammaRIIa and explains and reconciles the diverse and conflicting data
      presented in the literature.

PMID- 15486315
TI  - Intracellular labile iron modulates adhesion of human monocytes to human
      endothelial cells.
AB  - OBJECTIVE: Elevated iron stores and high plasma iron concentration have been
      linked to an increased risk of atherosclerosis. Iron may thereby affect the
      interaction of monocytes to endothelium, an initial event in the formation of
      atherosclerotic plaques. METHODS AND RESULTS: Addition of 10 mumol/L non
      transferrin-bound iron to the incubation medium caused a 2-fold increase in
      monocyte adhesion to human umbilical vein endothelial cells (HUVECs). A
      concordant increase in the expression of the following adhesion molecules was
      observed: vascular cell adhesion molecule-1, intercellular adhesion molecule-1,
      and endothelial selectin on HUVECs as well as very late antigen-4, and lymphocyte
      function-associated antigen-1 on monocytes. The inclusion of either deferiprone
      or salicylaldehyde isonicotinoylhydrazone counteracted these effects.
      Intracellular iron chelation by deferoxamine was completed only after 10 hours of
      incubation, shown by reversal of iron-quenched intracellular calcein signal, and
      concurrently the effects of iron were blunted. The membrane-impermeable chelator,
      diethylenetriamine pentaaceticacid, failed to negate iron effects, even after 48
      hours of treatment. Furthermore, only membrane-permeable superoxide or hydroxyl
      radical scavengers were capable of preventing HUVEC activation by iron.
      CONCLUSIONS: Non-transferrin-bound iron increases the level of intracellular
      labile iron, which promotes monocyte recruitment to endothelium and may thereby
      contribute to the pathogenesis of atherosclerosis. Iron-induced adhesion molecule
      expression was observed, and this event may involve the production of oxygen
      radicals.

PMID- 15486316
TI  - Transactivation of epidermal growth factor receptor mediates catecholamine
      induced growth of vascular smooth muscle.
AB  - Stimulation of alpha1-adrenoceptors induces proliferation of vascular smooth
      muscle cells (SMCs) and contributes to arterial remodeling. Although activation
      of NAD(P)H oxidase and generation of reactive oxygen species (ROS) are required,
      little is known about this pathway. In this study, we examined the hypothesis
      that epidermal growth factor receptor (EGFR) transactivation and extracellular
      regulated kinases (ERK) are involved in alpha1-adrenoceptor-mediated SMC growth.
      Phenylephrine increased protein synthesis in association with a rapid (< or =5
      minutes) and sustained (> or =60 minutes) doubling of phosphorylation of EGFR and
      ERK1/2, but not p38 or JNK in the media of rat aorta maintained in organ culture.
      Antagonists of EGFR phosphotyrosine activity (AG-1478) and ERK phosphorylation
      (PD-98059, U-0126) abolished phenylephrine-induced protein synthesis, whereas
      antagonists of p38 or JNK phosphorylation had no specific effect. A competitive
      antagonist (P22) for heparin binding EGF-like growth factor (HB-EGF) blocked
      phenylephrine-induced protein synthesis, as did downregulation of pro-HB-EGF
      (CRM197). Phenylephrine-induced protein synthesis was inhibited by neutralizing
      antibody to HB-EGF and absent in HB-EGF-/- SMCs. Inhibitors of metalloproteinases
      (BiPS, KB-R7785) also blocked adrenergic growth. The neutralizing antibody
      against HB-EGF had no effect on the two-fold increase in ROS generation induced
      by phenylephrine (DCF fluorescence), suggesting that stimulation of NAD(P)H
      oxidase by alpha1-adrenoceptor occupation precedes HB-EGF release. Cell culture
      studies confirmed and extended these findings. These data suggest that alpha1
      adrenoceptor-mediated SMC growth requires ROS-dependent shedding of HB-EGF,
      transactivation of EGFR, and activation of the MEK1/2-dependent MAP kinase
      pathway. This trophic pathway may link sympathetic activity to arterial wall
      growth in adaptive remodeling and hypertrophic disease.

PMID- 15486317
TI  - A G/C element mediates repression of the SM22alpha promoter within phenotypically
      modulated smooth muscle cells in experimental atherosclerosis.
AB  - A hallmark of smooth muscle cell (SMC) phenotypic switching in atherosclerotic
      lesions is suppression of SMC differentiation marker gene expression. Yet little
      is known regarding the molecular mechanisms that control this process. Here we
      show that transcription of the SMC differentiation marker gene SM22alpha is
      reduced in atherosclerotic lesions and identify a cis regulatory element in the
      SM22alpha promoter required for this process. Transgenic mice carrying the
      SM22alpha promoter-beta-galactosidase (beta-gal) reporter transgene were crossed
      to apolipoprotein E (ApoE)-/- mice. Cells of the fibrous cap, intima, and
      underlying media showed complete loss of beta-gal activity in advanced
      atherosclerotic lesions. Of major significance, mutation of a G/C-rich cis
      element in the SM22alpha promoter prevented the decrease in SM22alpha promoter
      beta-gal reporter transgene expression, including in cells that compose the
      fibrous cap of the lesion and in medial cells in proximity to the lesion. To
      begin to assess mechanisms whereby the G/C repressor element mediates suppression
      of SM22alpha in atherosclerosis, we tested the hypothesis that effects may be
      mediated by platelet-derived growth factor (PDGF)-BB-induced increases in the G/C
      binding transcription factor Sp1. Consistent with this hypothesis, results of
      studies in cultured SMCs showed that: (1) PDGF-BB increased expression of Sp1;
      (2) PDGF-BB and Sp1 profoundly suppressed SM22alpha promoter activity as well as
      smooth muscle myosin heavy chain promoter activity through mechanisms that were
      at least partially dependent on the G/C cis element; and (3) a short interfering
      RNA to Sp1 increased basal expression and attenuated PDGF-BB induced suppression
      of SM22alpha. Together, these results support a model whereby a G/C repressor
      element within the SM22alpha promoter mediates transcriptional repression of this
      gene within phenotypically modulated SMCs in experimental atherosclerosis and
      provide indirect evidence implicating PDGF-BB and Sp1 as possible mediators of
      these effects.

PMID- 15486318
TI  - Plasma cholesteryl esters provided by lecithin:cholesterol acyltransferase and
      acyl-coenzyme a:cholesterol acyltransferase 2 have opposite atherosclerotic
      potential.
AB  - Evidence suggests that ACAT2 is a proatherogenic enzyme that contributes
      cholesteryl esters (CEs) to apoB-containing lipoproteins, whereas LCAT is an
      antiatherogenic enzyme that facilitates reverse cholesterol transport by
      esterifying free cholesterol on HDL particles. We hypothesized that deletion of
      LCAT and ACAT2 would lead to absence of plasma CEs and reduced atherosclerosis.
      To test this hypothesis, ACAT2-/- LCAT-/- LDLr-/-, ACAT2-/- LDLr-/-, and LCAT-/-
      LDLr-/- mice were fed a 0.15% cholesterol diet for 20 weeks. In comparison to
      LDLr-/- mice, the total plasma cholesterol (TPC) of ACAT2-/- LCAT-/- LDLr-/- mice
      was 67% lower because of the complete absence of plasma CEs, leading to 94% less
      CE accumulation in the aorta. In the LCAT-/- LDLr-/- mice, TPC and
      atherosclerosis were significantly higher because of increased accumulations of
      ACAT2-derived CE. In ACAT2-/- LDLr-/- mice, again compared with LDLr-/- mice, TPC
      was 19% lower, whereas atherosclerosis was 88% lower. Therefore, the absence of
      ACAT2 led to a significant reduction in TPC although benefits in reduction of
      atherosclerosis were much more pronounced. Overall, the data suggest that ACAT2
      derived CE is the predominant atherogenic lipid in blood, and that an important
      goal for prevention of atherosclerosis is to limit ACAT2-derived CE accumulation
      in lipoproteins.

PMID- 15486319
TI  - Silent information regulator 2alpha, a longevity factor and class III histone
      deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes.
AB  - Yeast silent information regulator 2 (Sir2), a nicotinamide adenine dinucleotide
      dependent histone deacetylase (HDAC) and founding member of the HDAC class III
      family, functions in a wide array of cellular processes, including gene
      silencing, longevity, and DNA damage repair. We examined whether or not the
      mammalian ortholog Sir2 affects growth and death of cardiac myocytes. Cardiac
      myocytes express Sir2alpha predominantly in the nucleus. Neonatal rat cardiac
      myocytes were treated with 20 mmol/L nicotinamide (NAM), a Sir2 inhibitor, or 50
      nmol/L Trichostatin A (TSA), a class I and II HDAC inhibitor. NAM induced a
      significant increase in nuclear fragmentation (2.2-fold) and cleaved caspase-3,
      as did sirtinol, a specific Sir2 inhibitor, and expression of dominant-negative
      Sir2alpha. TSA also modestly increased cell death (1.5-fold) but without
      accompanying caspase-3 activation. Although TSA induced a 1.5-fold increase in
      cardiac myocyte size and protein content, NAM reduced both. In addition, NAM
      caused acetylation and increases in the transcriptional activity of p53, whereas
      TSA did not. NAM-induced cardiac myocyte apoptosis was inhibited in the presence
      of dominant-negative p53, suggesting that Sir2alpha inhibition causes apoptosis
      through p53. Overexpression of Sir2alpha protected cardiac myocytes from
      apoptosis in response to serum starvation and significantly increased the size of
      cardiac myocytes. Furthermore, Sir2 expression was increased significantly in
      hearts from dogs with heart failure induced by rapid pacing superimposed on
      stable, severe hypertrophy. These results suggest that endogenous Sir2alpha plays
      an essential role in mediating cell survival, whereas Sir2alpha overexpression
      protects myocytes from apoptosis and causes modest hypertrophy. In contrast,
      inhibition of endogenous class I and II HDACs primarily causes cardiac myocyte
      hypertrophy and also induces modest cell death. An increase in Sir2 expression
      during heart failure suggests that Sir2 may play a cardioprotective role in
      pathologic hearts in vivo.

PMID- 15486320
TI  - Flow: the signal of life.

PMID- 15486321
TI  - Cardiovascular ecto-5'-nucleotidase: an end to 40 years in the wilderness?

PMID- 15486322
TI  - What causes sudden death in heart failure?
AB  - Patients with heart failure experience a number of changes in the electrical
      function of the heart that predispose to potentially lethal cardiac arrhythmias.
      Action potential prolongation, the result of functional downregulation of K
      currents, and aberrant Ca2+ handling is a recurrent theme. Significant
      alterations in conduction and activation of a number of initially adaptive but
      ultimately maladaptive signaling cascades contribute to the generation of a
      highly arrhythmogenic substrate. We review the changes in active and passive
      membrane properties, neurohumoral signaling, and genetic determinants that
      predispose to sudden arrhythmic death in patients with heart failure and
      highlight the critical unanswered questions that are ripe for future
      investigation.

PMID- 15486323
TI  - Antiinflammatory properties of HDL.
AB  - There are several well-documented functions of high-density lipoprotein (HDL)
      that may explain the ability of these lipoproteins to protect against
      atherosclerosis. The best recognized of these is the ability of HDL to promote
      the efflux of cholesterol from cells. This process may minimize the accumulation
      of foam cells in the artery wall. However, HDL has additional properties that may
      also be antiatherogenic. For example, HDL is an effective antioxidant. The major
      proteins of HDL, apoA-I and apoA-II, as well as other proteins such as
      paraoxonase that cotransport with HDL in plasma, are well-known to have
      antioxidant properties. As a consequence, HDL has the capacity to inhibit the
      oxidative modification of low-density lipoprotein (LDL) in a process that reduces
      the atherogenicity of these lipoproteins. HDL also possesses other
      antiinflammatory properties. By virtue of their ability to inhibit the expression
      of adhesion molecules in endothelial cells, they reduce the recruitment of blood
      monocytes into the artery wall. These antioxidant and antiinflammatory properties
      of HDL may be as important as its cholesterol efflux function in terms of
      protecting against the development of atherosclerosis.

PMID- 15486326
TI  - Association between pulse pressure values during the acute stroke stage and
      stroke outcome.

PMID- 15486327
TI  - ASPECTS on CTA source images versus unenhanced CT: added value in predicting
      final infarct extent and clinical outcome.
AB  - BACKGROUND AND PURPOSE: The Alberta Stroke Program Early CT Score (ASPECTS) is a
      grading system to assess ischemic changes on CT in acute ischemic stroke. CT
      angiography-source images (CTA-SI) predict final infarct volume. We examined
      whether the final infarct ASPECTS and clinical outcome were more related to acute
      CTA-SI ASPECTS than to the acute noncontrast CT (NCCT) ASPECTS. METHODS: ASPECTS
      was assigned by 2 raters on the acute NCCT, CTA-SI, and follow-up imaging. The
      mean baseline ASPECTS of acute NCCT and CTA-SI was compared with the follow-up
      ASPECTS. Rate ratios (RRs) were used to quantify the relationship between the
      dichotomized baseline ASPECTS (categorized as 0 to 7 versus 8 to 10) and
      favorable patient outcome. RESULTS: Thirty-nine patients were recruited. Proximal
      occlusion (internal carotid artery or middle cerebral artery) was seen in 62%, M2
      occlusion in 18%, and no occlusion was seen in 20% of patients. The median time
      between symptom onset and imaging was 1.9 (1.2 to 2.5) hours. There was a
      significantly larger difference of 1.4 between the mean baseline NCCT and CTA-SI
      ASPECTS in patients who had more ischemic changes (follow-up ASPECTS=0 to 3) than
      a difference of 0.6 in patients who had near-to-normal CT scans (follow-up
      ASPECTS=8 to 10). The rate of favorable outcome for acute NCCT ASPECTS of 8 to 10
      was 51.8% versus 25.0% for 0 to 7 (RR, 2.1, 95% CI: 0.7 to 5.9, P=0.12). For
      acute CTA-SI ASPECTS of 8 to 10, the rate of favorable outcome was 58.8% versus
      31.8% for 0 to 7 (RR, 1.8, 95% CI: 0.9 to 3.8, P=0.09). CONCLUSIONS: CTA-SI
      ASPECTS provides added information in the prediction of final infarct size.

PMID- 15486328
TI  - The MATCH study results in the context of secondary stroke prevention.

PMID- 15486330
TI  - Treatment of constipation and fecal incontinence in stroke patients: randomized
      controlled trial.
AB  - BACKGROUND AND PURPOSE: Despite its high prevalence in stroke survivors, there is
      little clinical research on bowel dysfunction in this population. This is the
      first randomized controlled trial to evaluate treatment of constipation and fecal
      incontinence in stroke survivors. METHODS: Stroke patients with constipation or
      fecal incontinence were identified by screening questionnaire (122 community, 24
      stroke rehabilitation inpatients) and randomized to intervention or routine care
      (73 per group). The intervention consisted of a 1-off structured nurse assessment
      (history and rectal examination), leading to targeted patient/carer education
      with booklet and provision of diagnostic summary and treatment recommendations
      (after consultation with geriatrician) to patient's general practitioner (GP)+/
      ward physician. RESULTS: Percentage of bowel movements (BMs) per week graded as
      "normal" by participants in a prospective 1-week stool diary was significantly
      higher in intervention versus control patients at 6 months (72% versus 55%;
      P=0.027), as was mean number of BMs per week (5.2 versus 3.6; P=0.005). There was
      no significant reduction in fecal incontinence, although numbers were small. At
      12 months, intervention patients were more likely to be modifying their diets
      (odds ratio [OR], 3.1 [1.2 to 8.0]) and fluid intake (OR, 4.2 [1.4 to 12.2]) to
      control their bowels and to have visited their GP for their bowel problem (OR,
      5.0 [1.4 to 17.5]). GP prescribing of laxatives and suppositories was
      significantly influenced at 12 months. CONCLUSIONS: A single clinical/educational
      nurse intervention in stroke patients effectively improved symptoms of bowel
      dysfunction up to 6 months later, changed bowel-modifying lifestyle behaviors up
      to 12 months later, and influenced patient-GP interaction and physician
      prescribing patterns.

PMID- 15486331
TI  - Near-infrared spectroscopy in stroke: from research to clinical practice.

PMID- 15486332
TI  - Molecular identification of the ischemic penumbra.
AB  - Review of results of experimental and clinical studies indicates that the
      penumbra of physiologically impaired but potentially salvageable tissue
      surrounding the central core of focal cerebral ischemia that develops shortly
      after onset of major conducting vessel occlusion is complex and dynamic with
      severity and duration thresholds for hypoxic stress and injury that are specific
      to tissue site, cell type, molecular pathway or gene expression investigated and
      efficiency of collateral or residual flow and reperfusion. Imaging methods that
      have been utilized in vivo to identify penumbra and predict response to
      reperfusion and other protective therapies include magnetic resonance
      spectroscopy, diffusion- and perfusion-MRI as well as positron emission
      tomography. However, resolution of focal lesions characterized by lactic acidosis
      or cellular edema does not predict tissue survival, and imaging thresholds for
      resuscitation after reperfusion have not been determined experimentally. HSP-70
      stress protein induction represents an endogenous protective mechanism that
      occurs in penumbra but not core neurones. A robust protective effect has been
      demonstrated during focal ischemia in transgenic mice overexpressing HSP-70
      perhaps by suppressing early cytochrome c release. Delayed manganese mediated
      striatal neurodegeneration can be detected with T1 MRI after brief episodes of
      transient focal ischemia. Future studies may define endogenous cytotoxic and
      cytoprotective molecular penumbras that can be exploited to improve outcome after
      temporary focal ischemia.

PMID- 15486333
TI  - Transient ischemic attacks are more than "ministrokes".
AB  - BACKGROUND AND PURPOSE: Transient ischemic attacks (TIAs) are warning signs of
      stroke. Recently, the hypothesis was raised that TIA bears a significant risk for
      death and dependence and requires the same complex diagnostic workup as a
      complete stroke. METHODS: We prospectively collected pre- and in-hospital
      procedures, symptoms, outcome, complications, and therapies from a representative
      sample of all stroke-treating hospitals (n=82) in southwest Germany. Follow-up
      was attempted 6 months after discharge. End points were death or dependence in
      activities of daily living (Barthel Index <95, modified Rankin Scale (mRS) of 3
      to 6, or institutionalization in a nursing home). RESULTS: 1380 TIA patients and
      3855 stroke patients entered the database. During hospital stay, stroke incidence
      was 8% for TIA patients and another 5% within the first half-year. Similarly, for
      ischemic stroke (IS) patients these figures were 7% and 6% (P>0.05),
      respectively. Two percent of TIA patients died in hospital (5% afterward)
      compared with 9% of stroke patients (10% afterward, P<0.001). Seventeen percent
      TIA compared with 38% IS patients (P<0.05) were dependent at follow-up. Whereas
      an estimated preexisting deficit (mRS >2) was the strongest predictor for death
      or disability (baseline mRS odds ratio, 4.1; 95% CI, 2.3 to 7.2), admission to a
      stroke unit was a valid predictor for survival and independence (odds ratio, 0.4;
      95% CI, 0.2 to 0.9). CONCLUSIONS: These data from a large, multicenter,
      nonselected, observational study underscore the "not so benign" prognosis for TIA
      patients. There is a relevant individual risk of early stroke, death, or
      disability in TIA patients. Management and treatment strategies are similar for
      both TIA and acute stroke.

PMID- 15486335
TI  - Brain-machine and brain-computer interfaces.
AB  - The idea of connecting the human brain to a computer or machine directly is not
      novel and its potential has been explored in science fiction. With the rapid
      advances in the areas of information technology, miniaturization and
      neurosciences there has been a surge of interest in turning fiction into reality.
      In this paper the authors review the current state-of-the-art of brain-computer
      and brain-machine interfaces including neuroprostheses. The general principles
      and requirements to produce a successful connection between human and artificial
      intelligence are outlined and the authors' preliminary experience with a
      prototype brain-computer interface is reported.

PMID- 15486336
TI  - New insights into plant development in New England.
AB  - This year, the biannually organized FASEB meeting 'Mechanisms in Plant
      Development' took place in August in Vermont, USA, organized by Martin Hulskamp
      (University of Koln, Koln, Germany) and John Schiefelbein (University of
      Michigan, Ann Arbor, MI, USA). The meeting covered numerous topics, ranging from
      patterning and differentiation to the evolution of developmental mechanisms.
      Despite apparent distinctions between the sessions, many of the talks were broad
      ranging and most highlighted unifying developmental concepts.

PMID- 15486337
TI  - BRL1 and BRL3 are novel brassinosteroid receptors that function in vascular
      differentiation in Arabidopsis.
AB  - Plant steroid hormones, brassinosteroids (BRs), are perceived by the plasma
      membrane-localized leucine-rich-repeat-receptor kinase BRI1. Based on sequence
      similarity, we have identified three members of the BRI1 family, named BRL1, BRL2
      and BRL3. BRL1 and BRL3, but not BRL2, encode functional BR receptors that bind
      brassinolide, the most active BR, with high affinity. In agreement, only BRL1 and
      BRL3 can rescue bri1 mutants when expressed under the control of the BRI1
      promoter. While BRI1 is ubiquitously expressed in growing cells, the expression
      of BRL1 and BRL3 is restricted to non-overlapping subsets of vascular cells. Loss
      of-function of brl1 causes abnormal phloem:xylem differentiation ratios and
      enhances the vascular defects of a weak bri1 mutant. bri1 brl1 brl3 triple
      mutants enhance bri1 dwarfism and also exhibit abnormal vascular differentiation.
      Thus, Arabidopsis contains a small number of BR receptors that have specific
      functions in cell growth and vascular differentiation.

PMID- 15486338
TI  - Clinical usefulness of home oximetry compared with polysomnography for assessment
      of sleep apnea.
AB  - The practical purpose of diagnostic assessment in most cases of obstructive sleep
      apnea is to predict which patients have symptoms that will improve on treatment.
      We measured the accuracy with which clinicians make this prediction using
      polysomnography compared with oximeter-based home monitoring. Patients referred
      to a sleep center with suspicion of symptomatic obstructive sleep apnea were
      randomized to have polysomnography or home monitoring. Patients with comorbidity
      or physiologic consequences of sleep apnea were excluded. Sleep specialists
      estimated the likelihood of success of treatment as greater than 50% (predicted
      success) or less than 50% (predicted failure) on the basis of clinical data and
      test results. All patients were treated for 4 weeks with autoadjusting continuous
      positive airway pressure. Success was defined as an increase greater than 1.0 in
      Sleep Apnea Quality of Life Index. Correct prediction rates were compared. Two
      hundred eighty-eight patients were enrolled. Initial patient characteristics,
      compliance, and improvement in quality of life at 4 weeks were not different in
      the two groups. The correct prediction rate was 0.61 with polysomnography and
      0.64 with home monitoring (not significant). We conclude that the ability of
      physicians to predict the outcome of continuous positive airway treatment in
      individual patients is not significantly better with polysomnography than with
      home oximeter-based monitoring.

PMID- 15486339
TI  - Pulmonary blood flow heterogeneity during hypoxia and high-altitude pulmonary
      edema.
AB  - Uneven hypoxic pulmonary vasoconstriction has been proposed to expose parts of
      the pulmonary capillary bed to high pressure and vascular injury in high-altitude
      pulmonary edema (HAPE). We hypothesized that subjects with a history of HAPE
      would demonstrate increased heterogeneity of pulmonary blood flow during hypoxia.
      A functional magnetic resonance imaging technique (arterial spin labeling) was
      used to quantify spatial pulmonary blood flow heterogeneity in three subject
      groups: (1) HAPE-susceptible (n = 5), individuals with a history of physician
      documented HAPE; (2) HAPE-resistant (n = 6), individuals with repeated high
      altitude exposure without illness; and (3) unselected (n = 6), individuals with a
      minimal history of altitude exposure. Data were collected in normoxia and after
      5, 10, 20, and 30 minutes of normobaric hypoxia FI(O(2)) = 0.125. Relative
      dispersion (SD/mean) of the signal intensity was used as an index of perfusion
      heterogeneity. Oxygen saturation was not different between groups during hypoxia.
      Relative dispersion was not different between groups (HAPE-susceptible 0.94 +/-
      0.05, HAPE-resistant 0.94 +/- 0.05, unselected 0.87 +/- 0.06; means +/- SEM)
      during normoxia, but it was increased by hypoxia in HAPE-susceptible (to 1.10 +/-
      0.05 after 30 minutes, p < 0.0001) but not in HAPE-resistant (0.91 +/- 0.05) or
      unselected subjects (0.87 +/- 0.05). HAPE-susceptible individuals have increased
      pulmonary blood flow heterogeneity in acute hypoxia, consistent with uneven
      hypoxic pulmonary vasoconstriction.

PMID- 15486340
TI  - Decline in lung function in the Busselton Health Study: the effects of asthma and
      cigarette smoking.
AB  - Asthma in adults may be associated with chronic airflow obstruction, possibly
      resulting from airway disease in early life and/or a greater rate of decline in
      lung function in adult life compared with those with asthma. Treatment and
      cigarette smoking may also influence the rate of decline of lung function. The
      aim of this analysis was to examine the level and rate of decline in lung
      function in relationship to asthma and cigarette smoking in adults. Subjects (n =
      9,317) had participated as adults (> 18 years) in one or more of the cross
      sectional Busselton Health Surveys between 1966 and 1981 or in the follow-up
      study of 1994/1995. The effects of sex, doctor-diagnosed asthma, smoking status,
      and anthropometric data on the level and rate of decline in FEV1 were examined in
      a linear mixed effects model. At the age of 19 years, FEV1 was reduced in
      subjects with asthma but was similar in smokers and nonsmokers. Males, taller
      subjects, smokers, and subjects with asthma had greater declines in FEV1 with
      age. Smoking and asthma had additive but not multiplicative effects on decline.
      Thus, asthma is associated with reduced lung function at the beginning of adult
      life as well as an increased rate of decline during adult life.

PMID- 15486341
TI  - Association of tumor necrosis factor-alpha polymorphisms and ozone-induced change
      in lung function.
AB  - Ozone is a major air pollutant with adverse health effects which exhibit marked
      inter-individual variability. In mice, regions of genetic linkage with ozone
      induced lung injury include the tumor necrosis factor-alpha (TNF), lymphotoxin
      alpha (LTA), Toll-like receptor 4 (TLR4), superoxide dismutase (SOD2), and
      glutathione peroxidase (GPX1) genes. We genotyped polymorphisms in these genes in
      51 individuals who had undergone ozone challenge. Mean change in FEV1 with ozone
      challenge, as a percentage of baseline, was -3% in TNF -308G/A or A/A
      individuals, compared with -9% in G/G individuals (p = 0.024). When considering
      TNF haplotypes, the smallest change in FEV1 with ozone exposure was associated
      with the TNF haplotype comprising LTA +252G/TNF -1031T/TNF -308A/TNF -238G. This
      association remained statistically significant after correction for age, sex,
      disease, and ozone concentration (p = 0.047). SOD2 or GPX1 genotypes were not
      associated with lung function, and the TLR4 polymorphism was too infrequent to
      analyze. The results of this study support TNF as a genetic factor for
      susceptibility to ozone-induced changes in lung function in humans, and has
      potential implications for stratifying health risks of air pollution.

PMID- 15486342
TI  - Enteroendocrine cell expression of a cholecystokinin gene construct in transgenic
      mice and cultured cells.
AB  - CCK is predominantly expressed in subsets of endocrine cells in the intestine and
      neurons in the brain. We evaluated the expression of a CCK gene construct in
      transgenic mice and cultured cells to identify a genomic region that directs
      correct tissue- and cell-specific expression in enteroendocrine cells. The CCKL1
      transgene contained 6.4 kb of mouse Cck fused to lacZ. Expression was evaluated
      in three transgenic lines (J11, J12, J14) by measurement of beta-galactosidase in
      tissue homogenates and frozen sections. Correct tissue-specific expression was
      observed, with beta-galactosidase activity detected in intestine and brain.
      However, there were differences seen in cell-specific expression in the
      intestine. Line J14 exhibited expression in CCK-endocrine cells, with expressing
      cells arising at the normal time during fetal development. However, transgene
      expression in line J12 intestine was limited to neurons of the enteric nervous
      system, which reflect an early fetal expression pattern for CCK. Analysis of an
      additional 15 transgenic founder mice demonstrated intestinal expression in 40%
      of transgenics, with expressing mice following either an endocrine cell pattern
      or a neuronal pattern in approximately equal numbers. CCKL1 transfection analysis
      in cultured cells also demonstrated enteroendocrine cell expression, with 100
      fold enhanced activity in the enteroendocrine cell line STC-1 compared with
      nonendocrine cell lines. The results suggest that the minimal cis-regulatory DNA
      elements necessary for appropriate CCK expression in enteroendocrine cells reside
      within the 6.4-kb mouse genomic fragment.

PMID- 15486343
TI  - Agonist-induced association of tropomyosin with protein kinase Calpha in colonic
      smooth muscle.
AB  - Smooth muscle contraction regulated by myosin light chain phosphorylation is also
      regulated at the thin-filament level. Tropomyosin, a thin-filament regulatory
      protein, regulates contraction by modulating actin-myosin interactions. Present
      investigation shows that acetylcholine induces PKC-mediated and calcium-dependent
      phosphorylation of tropomyosin in colonic smooth muscle cells. Our data also
      shows that acetylcholine induces a significant and sustained increase in PKC
      mediated association of tropomyosin with PKCalpha in the particulate fraction of
      colonic smooth muscle cells. Immunoblotting studies revealed that in colonic
      smooth muscle cells, there is no significant change in the amount of tropomyosin
      or actin in particulate fraction in response to acetylcholine, indicating that
      the increased association of tropomyosin with PKCalpha in the particulate
      fraction may be due to acetylcholine-induced translocation of PKCalpha to the
      particulate fraction. To investigate whether the association of PKCalpha with
      tropomyosin was due to a direct interaction, we performed in vitro direct binding
      assay. Tropomyosin cDNA amplified from colonic smooth muscle mRNA was expressed
      as GST-tropomyosin fusion protein. In vitro binding experiments using GST
      tropomyosin and recombinant PKCalpha indicated direct interaction of tropomyosin
      with PKCalpha. PKC-mediated phosphorylation of tropomyosin and direct interaction
      of PKCalpha with tropomyosin suggest that tropomyosin could be a substrate for
      PKC. Phosphorylation of tropomyosin may aid in holding the slided tropomyosin
      away from myosin binding sites on actin, resulting in actomyosin interaction and
      sustained contraction.

PMID- 15486344
TI  - COOH-terminal 26-amino acid residues of progastrin are sufficient for stimulation
      of mitosis in murine colonic epithelium in vivo.
AB  - Transgenic mice (hGAS) that overexpress human progastrin are more susceptible
      than wild-type mice (FVB/N) to the induction of colonic aberrant crypt foci (ACF)
      and adenomas by the chemical carcinogen azoxymethane. We have previously shown
      significantly increased levels of colonic mitosis in hGAS compared with FVB/N
      mice after gamma-radiation. To investigate whether the effects of progastrin
      observed in hGAS colon require the presence of other forms of circulating
      gastrin, we have crossed hGAS (hg(+/+)) with gastrin knockout (G(-/-)) mice to
      generate mice that express progastrin and no murine gastrin (G(-/-)hg(+/+)).
      After azoxymethane, G(-/-)hg(+/+) mice developed significantly more ACF than
      control G(-/-)hg(-/-) mice (which do not express any forms of gastrin). G(-/
      )hg(+/+) mice also exhibited significantly increased colonic mitosis both before
      and after exposure to 8 Gray Gy gamma-radiation or 50 mg/kg azoxymethane compared
      with G(-/-)hg(-/-). Treatment of G(-/-)hg(-/-) mice with synthetic progastrin
      (residues 21-101 of human preprogastrin) or G17 extended at its COOH terminus
      corresponding to the COOH-terminal 26-amino-acid residues of human preprogastrin
      (residues 76-101, G17-CFP) resulted in continued colonic epithelial mitosis after
      gamma-radiation, whereas glycine-extended gastrin-17 and the COOH-terminal
      tryptic fragment of progastrin [human preprogastrin-(96-101)] had no effect.
      Immunoneutralization with an antibody against G17-CFP before gamma-radiation
      significantly decreased colonic mitosis in G(-/-)hg(+/+) mice to levels similar
      to G(-/-)hg(-/-). We conclude that progastrin does not require the presence of
      other forms of gastrin to exert proliferative effects on colonic epithelia and
      that the portion of the peptide responsible for these effects is contained within
      amino acid residues 76-101 of human preprogastrin.

PMID- 15486345
TI  - Impaired cytoprotective function of muscle in human gallbladders with cholesterol
      stones.
AB  - Acute cholecystitis develops in gallbladders (GB) with excessive bile cholesterol
      (Ch). Increased membrane Ch content affects membrane function and may affect
      PGE(2) receptors involved in the cytoprotection against acute inflammation. This
      study was aimed at determining whether the cytoprotective response to PGE(2) is
      affected by lithogenic bile with Ch. Muscle cells from human GB with cholesterol
      stones (ChS) or pigment stones (PS) were obtained by enzymatic digestion. PGE(2)
      levels were measured by radioimmunoassay, and activities of superoxide dismutase
      (SOD) and catalase were assayed by spectrophotometry. The contraction in response
      to H(2)O(2) in muscle cells from PS was 14 +/- 0.3%, not different from normal
      controls, and decreased after the cells were incubated with Ch-rich liposomes (P
      < 0.05), which increase the Ch content in the plasma membranes. In muscle cells
      from GB with ChS, H(2)O(2)-induced contraction was only 9.2 +/- 1.3% and
      increased to 14 +/- 0.2% after Ch-free liposome treatment to remove Ch from the
      plasma membranes (P < 0.01). H(2)O(2) caused a similar increase in the levels of
      lipid peroxidation and PGE(2) content in muscle cells from GBs with ChS and PS.
      However, the activities of SOD and catalase were significantly lower in muscle
      cells from GBs with ChS compared with those with PS. The binding capacity of
      PGE(2) receptors was also significantly lower in muscle cells from GBs with ChS
      compared with those with PS. In conclusion, the cytoprotective response to
      reactive oxygen species is reduced in muscle cells from GBs with ChS despite a
      normal increase in the cellular levels of PGE(2). This impaired cytoprotective
      response may be due to a dysfunction of PGE(2) receptors with decreased binding
      capacity resulting from excessive Ch levels in the plasma membrane.

PMID- 15486346
TI  - Role of l-Ca(2+) channels in intestinal pacing in wild-type and W/W(V) mice.
AB  - Rhythmic contractions generating transit in the digestive tract are paced by a
      network of cells called interstitial cells of Cajal (ICC) found in the myenteric
      plexus (MP). ICC generate cyclic depolarizations termed "slow waves" that are
      passively transmitted to the smooth muscle to initiate contractions. The opening
      of l-Ca(2+) channels are believed to be primarily responsible for the influx of
      calcium generating a contraction in smooth muscle. However, l-Ca(2+) channels are
      not thought to be important in generating the pacing current found in ICC. Using
      intact segments of circular (CM) and longitudinal (LM) muscle from wild-type mice
      and mice lacking c-kit kinase (W/W(V)), we found that l-Ca(2+) channel currents
      are required for pacing at normal frequencies to occur. Application of 1 muM
      nicardipine caused a significant decrease in contraction amplitude and frequency
      in LM and CM that was successfully blocked with BAY K 8644. Nicardipine also
      abolished the pacing gradient found throughout the intestines, resulting in a
      uniform contraction frequency of 30-40/minute. Stimulating l-Ca(2+) channels with
      BAY K 8644 neither removed nor recovered the pacing gradient. W/W(V) mice, which
      lack ICC-MP, also exhibited a pacing gradient in LM. Application of nicardipine
      to LM segments of W/W(V) mouse intestine did not reduce pacing frequency, and in
      jejunum, resulted in a slight increase. BAY K 8644 did not affect pacing
      frequency in W/W(V) tissue. In conclusion, we found that l-Ca(2+) channel
      activity was required for normal pacing frequencies and to maintain the pacing
      frequency gradient found throughout the intestines in wild-type but not in W/W(V)
      mouse intestine.

PMID- 15486347
TI  - Nitric oxide mediates increased P-glycoprotein activity in interferon-{gamma}
      stimulated human intestinal cells.
AB  - Patients with refractory inflammatory bowel disease (IBD) exhibit increased
      expression of intestinal P-glycoprotein (P-gp) as well as elevated luminal IFN
      gamma and nitric oxide (NO) levels. Using the in vitro Caco-2 cell culture model,
      we investigated whether these pathological mediators associated with the etiology
      of IBD affect functional activity of intestinal efflux systems. IFN-gamma reduced
      cellular uptake of cyclosporin A (CysA) but not methotrexate (MTX) in a time- and
      concentration-dependent manner. Simultaneously, P-gp expression increased by
      approximately twofold. Coincubation with the inducible NO synthase inhibitor l
      N(6)-(1-iminoethyl)lysine (l-NIL) dramatically reduced production of
      intracellular NO in response to IFN-gamma stimulus. The presence of l-NIL also
      abrogated the cytokine-mediated increase in P-gp expression and function
      suggesting that NO is required for IFN-gamma-mediated activation of this efflux
      system. Exposure of Caco-2 cells to the chemical NO donor S-nitroso-N
      acetylpenicillamine (SNAP) produced a concentration-dependent decrease in
      intracellular CysA accumulation that was paralleled by an increase in P-gp
      expression. Both IFN-gamma and SNAP enhanced DNA binding of NF-kappaB, whereas
      inclusion of l-NIL dramatically decreased this cytokine-induced effect on NF
      kappaB binding. These results suggest that NO mediates IFN-gamma-induced increase
      in expression and function of intestinal P-gp in the human Caco-2 cell culture
      model by altering DNA binding of NF-kappaB, which may enhance transcription of
      the ABCB1 gene encoding for this efflux system.

PMID- 15486348
TI  - Activation of PPAR{gamma} by curcumin inhibits Moser cell growth and mediates
      suppression of gene expression of cyclin D1 and EGFR.
AB  - Colorectal cancer is a leading cause of cancer-related morbidity and mortality in
      the United States. Curcumin, the yellow pigment in turmeric, possesses inhibitory
      effects on growth of a variety of tumor cells by reducing cell proliferation and
      inducing apoptosis. Effects of the peroxisome proliferator-activated receptor
      gamma (PPARgamma) on stimulating cell differentiation and on inducing cell cycle
      arrest have attracted attention from the perspective of treatment and prevention
      of cancer. The aim of this study was to elucidate the mechanisms by which
      curcumin inhibits colon cancer cell growth. In the present report, we observed
      that curcumin, in a dose-dependent manner, inhibited the growth of Moser cells, a
      human colon cancer-derived cell line, and stimulated the trans-activating
      activity of PPARgamma. Further studies demonstrated that activation of PPARgamma
      was required for curcumin to inhibit Moser cell growth. Activation of PPARgamma
      mediated curcumin suppression of the expression of cyclin D1, a critical protein
      in the cell cycle, in Moser cells. In addition, curcumin blocked EGF signaling by
      inhibiting EGF receptor (EGFR) tyrosine phosphorylation and suppressing the gene
      expression of EGFR mediated by activation of PPARgamma. In addition to curcumin
      reduction of the level of phosphorylated PPARgamma, inhibition of cyclin D1
      expression played a major and significant role in curcumin stimulation of
      PPARgamma activity in Moser cells. Taken together, our results demonstrated for
      the first time that curcumin activation of PPARgamma inhibited Moser cell growth
      and mediated the suppression of the gene expression of cyclin D1 and EGFR. These
      results provided a novel insight into the roles and mechanisms of curcumin in
      inhibition of colon cancer cell growth and potential therapeutic strategies for
      treatment of colon cancer.

PMID- 15486349
TI  - Role of vagus nerve in postprandial antropyloric coordination in conscious dogs.
AB  - It is generally believed that gastric emptying of solids is regulated by a
      coordinated motor pattern between the antrum and pylorus. We studied the role of
      the vagus nerve in mediating postprandial coordination between the antrum and
      pylorus. Force transducers were implanted on the serosal surface of the body,
      antrum, pylorus, and duodenum in seven dogs. Dogs were given either a solid or a
      liquid meal, and gastroduodenal motility was recorded over 10 h. Gastric emptying
      was evaluated with radiopaque markers mixed with a solid meal. Dogs were treated
      with hexamethonium, N(G)-nitro-l-arginine methyl ester (l-NAME), or transient
      vagal nerve blockade by cooling. A postprandial motility pattern showed three
      distinct phases: early, intermediate, and late. In the late phase, profound
      pyloric relaxations predominantly synchronized with giant antral contractions
      that were defined as postprandial antropyloric coordination. A gastric emptying
      study revealed that the time at which gastric contents entered into the duodenum
      occurred concomitantly with antropyloric coordination. Treatment by vagal
      blockade or hexamethonium significantly reduced postprandial antral contractions
      and pyloric relaxations of the late phase. l-NAME changed pyloric motor patterns
      from relaxation dominant to contraction dominant. Solid gastric emptying was
      significantly attenuated by treatment with hexamethonium, l-NAME, and vagal
      blockade. Postprandial antropyloric coordination was not seen after feeding a
      liquid meal. It is concluded that postprandial antropyloric coordination plays an
      important role to regulate gastric emptying of a solid food. Postprandial
      antropyloric coordination is regulated by the vagus nerve and nitrergic neurons
      in conscious dogs.

PMID- 15486350
TI  - Exercise training improves overall physical fitness and quality of life in older
      women with coronary artery disease: just keep on moving?

PMID- 15486351
TI  - Benefits of cardiac rehabilitation in the elderly.

PMID- 15486352
TI  - Drugs prescribed for patients shouldn't be taken by caregivers!

PMID- 15486353
TI  - Nasal nitric oxide: clue to a diagnosis of ciliary dyskinesia.

PMID- 15486354
TI  - Plasma d-dimer for outcome assessment in patients with CAP: not a replacement for
      PSI.

PMID- 15486355
TI  - Noninvasive imaging modalities in coarctation of the aorta.

PMID- 15486356
TI  - Train-of-four to monitor neuromuscular blockade?

PMID- 15486357
TI  - Off label, on target?

PMID- 15486358
TI  - Exercise training improves overall physical fitness and quality of life in older
      women with coronary artery disease.
AB  - BACKGROUND: Older women with coronary artery disease (CAD) have reduced peak
      aerobic power (Vo(2)peak), muscle strength, and quality of life (QOL). Exercise
      interventions that can improve Vo(2)peak and muscle strength may also result in
      an improvement in QOL. This study compared the effect of aerobic training (AT) or
      combined aerobic and strength training (COMT) on Vo(2)peak, distance walked in 6
      min, upper- and lower-extremity maximal strength, and QOL in 18 women (age range,
      60 to 80 years) with documented CAD. METHODS: After baseline testing, subjects
      were randomly assigned to AT (treadmill and cycle exercise, n = 9) or COMT
      (treadmill and cycle exercise plus upper- and lower-extremity strength training,
      n = 9), and each group exercised 3 d/wk for 8 weeks. RESULTS: Both AT and COMT
      resulted in a similar increase in Vo(2)peak, distance walked in 6 min, lower
      extremity strength, and emotional and global QOL. COMT improved upper-extremity
      strength, and physical and social QOL, which was unchanged after AT. CONCLUSIONS:
      Older women with CAD should perform aerobic and strength training to attain
      optimal improvements in overall physical fitness and QOL.

PMID- 15486359
TI  - Risk stratification and prognostic implication of plasma biomarkers in
      nondiabetic patients with stable coronary artery disease: the role of high
      sensitivity C-reactive protein.
AB  - STUDY OBJECTIVES: To evaluate the implication of plasma biomarkers to future
      cardiovascular events in nondiabetic patients with stable coronary artery disease
      (CAD). Designs and settings: Prospective, follow-up study at a tertiary referral
      center. Patients and measurement: Serial plasma biomarkers including high
      sensitivity C-reactive protein (hsCRP), homocysteine, soluble adhesion molecules,
      von Willebrand factor, and lipid profiles were determined before coronary
      angiograms in a series of nondiabetic CAD patients with stable angina. Among
      them, 75 consecutive patients who received coronary revascularization (48
      coronary interventions and 27 coronary bypass surgeries) later and another 75 age
      and gender-matched patients who preferred medical treatment were both enrolled.
      In patients of each group, major cardiovascular events including cardiac death,
      nonfatal myocardial infarction, new or repeated coronary revascularization, and
      hospitalization for unstable angina, stroke, or peripheral artery disease were
      prospectively followed up for at least 6 months. RESULTS: Patients were followed
      up to 40 months (median, 18 months). The incidences of major cardiovascular
      events were similar between the two groups. For patients with medical treatment,
      plasma levels of hsCRP, homocysteine, low-density lipoprotein, and the ratio of
      total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C) were
      significantly higher in those with cardiovascular events than those without.
      However, only hsCRP > 0.1 mg/dL (relative risk [RR], 2.78; 95% confidence
      interval [CI], 1.21 to 6.41; p = 0.016) and TC/HDL-C ratio > 4.8 (RR, 2.42; 95%
      CI, 1.04 to 5.65; p = 0.041) were independent predictors by multivariable
      analysis. For patients with revascularization, basal plasma hsCRP levels were
      higher in those with cardiovascular events than those without (p = 0.04).
      However, no biochemical markers could predict future major cardiovascular events
      in these patients. CONCLUSIONS: In nondiabetic patients with CAD, basal plasma
      hsCRP levels were increased with future cardiovascular events regardless of
      different treatment strategies. Both plasma hsCRP level and TC/HDL-C ratio
      independently predict future cardiovascular events, confirming the role of plasma
      biomarkers in clinical risk stratification especially in patients with medical
      treatment.

PMID- 15486360
TI  - Sensitivity, specificity, positive predictive value, and negative predictive
      value of the dipyridamole sestamibi stress test comparing arterial to vein
      conduits.
AB  - STUDY OBJECTIVES: To determine the sensitivity, specificity, positive predictive
      value (PPV), and negative predictive value (NPV) of the dipyridamole stress test
      (DSST) in predicting > or = 50% obstruction of an internal mammary artery or new
      native coronary artery disease (CAD) compared with saphenous vein graft
      obstruction > or = 50% in patients with prior coronary artery surgery and
      symptoms. DESIGN: In 144 patients with prior coronary artery surgery who
      underwent a DSST within 8 +/- 7 days of coronary angiography performed because of
      cardiac symptoms, we investigated the sensitivity, specificity, PPV, and NPV of
      the DSST in predicting > or = 50% obstruction of an internal mammary artery or
      new native CAD (201 total arterial conduits) vs > or = 50% obstruction of
      saphenous vein grafts (total saphenous grafts = 246). SETTING: A university
      hospital. PATIENTS: The 144 patients included 88 men and 56 women, mean age 68 +/
      9 years (+/- SD). RESULTS: The DSST had a sensitivity of 81%, a specificity of
      87%, a PPV of 84%, and a NPV of 84% in predicting > or = 50% obstruction of an
      internal mammary artery or new native CAD. The DSST had a sensitivity of 88%, a
      specificity of 82%, a PPV of 86%, and a NPV of 85% in predicting > or = 50%
      obstruction of saphenous vein grafts. CONCLUSION: There was no significant
      difference in sensitivity, specificity, PPV, or NPV of the DSST in predicting >
      or = 50% obstruction of an internal mammary artery or new native CAD vs
      predicting > or = 50% obstruction of saphenous vein grafts in patients with prior
      coronary artery surgery and cardiac symptoms.

PMID- 15486361
TI  - Lung biopsy diagnosis of operative indication in secundum atrial septal defect
      with severe pulmonary vascular disease.
AB  - OBJECTIVE: Surgical indication was determined by lung biopsy in 91 patients with
      secundum atrial septal defect (ASD) and severe pulmonary hypertension > 70 mm Hg
      of pulmonary arterial peak pressure and/or pulmonary vascular resistance of > 8
      U/m(2). METHODS AND RESULTS: Pulmonary vascular disease (PVD) in ASD was
      classified into four types: (1) Musculoelastosis consisting of longitudinal
      muscle bundles and elastic fibers; surgery is indicated no matter how severely
      the peripheral small pulmonary arteries are occluded. Surgery was performed in
      all of the 20 patients, and the postoperative course was uneventful. (2)
      Plexogenic pulmonary arteriopathy: surgery is indicated for a PVD index < or =
      2.3. Surgery was performed in 25 of the 32 patients. The remaining seven patients
      for whom surgery was not indicated are under follow-up observation. No deaths
      have occurred among the 32 patients. (3) Thromboembolism of small pulmonary
      arteries: Surgery is indicated for all such cases. Surgery was indicated in all
      of the five patients. (4) Mixed type of plexogenic pulmonary arteriopathy and
      musculoelastosis: Surgery is indicated if the collateral is not observed. Surgery
      was performed in 15 of the 25 patients. The remaining 10 patients for whom
      surgery was not indicated are under follow-up observation. Nine of these 91
      patients associated with primary pulmonary hypertension were eliminated from this
      study. CONCLUSION: No deaths due to PVD occurred among the 82 patients who
      underwent lung biopsy diagnosis. Lung biopsy diagnosis is concluded to be very
      effective.

PMID- 15486362
TI  - Respiratory health survey of respiratory therapists.
AB  - STUDY OBJECTIVES: The purpose of this study was to determine whether respiratory
      therapists (RTs) had an elevated risk of respiratory symptoms and to determine
      the association of work exposures with symptoms. METHODS: Mailed questionnaire
      responses from 275 RTs working in British Columbia, Canada, were compared to
      those of 628 physiotherapists who had been surveyed previously. Analyses
      incorporated logistic regression analysis with adjustment for age, sex, smoking
      status, and childhood asthma. RESULTS: Compared to physiotherapists, RTs had over
      twice the risk of being woken by dyspnea, having wheeze, asthma attacks, and
      asthma diagnosed after entering the profession. Among RTs, two work factors
      associated with asthma were sterilizing instruments with glutaraldehyde-based
      solutions and the use of aerosolized ribavirin. RTs who used an oxygen tent or
      hood had the highest risk of asthma diagnosed after entering the profession (odds
      ratio [OR], 8.3; 95% confidence interval [CI], 12.6 to 26.0) and of asthma
      attacks in the last 12 months (OR, 3.6; 95% CI, 1.2 to 10.9). CONCLUSIONS: Our
      data suggest that RTs may be at an increased risk for asthma-like symptoms and
      for receiving a diagnosis of asthma since starting to work in their profession,
      possibly related to exposure to glutaraldehyde and aerosolized ribavirin.

PMID- 15486363
TI  - Nasal nitric oxide measurements to screen children for primary ciliary
      dyskinesia.
AB  - STUDY OBJECTIVE: To examine the usefulness of exhaled and nasal nitric oxide (NO)
      measurements to detect primary ciliary dyskinesia (PCD) in children. DESIGN AND
      METHODS: The study population consisted of 34 children with symptoms suggestive
      of PCD who were previously referred to our pediatric university respiratory
      disease clinic for a diagnostic workup including analysis of ciliary structure
      and function by respiratory mucosal biopsy. PCD was diagnosed in 17 of the 34
      children according to the ciliary biopsy results. Measurements of nasal and
      exhaled NO were performed according to European Respiratory Society and American
      Thoracic Society guidelines in the patients with and without biopsy-proven PCD,
      and also in 24 healthy age-matched subjects. RESULTS: Nasal NO was significantly
      lower in those children with proven PCD (geometric mean; 13.7 parts per billion
      [ppb]), compared to those who had negative biopsy results (132.7 ppb) and healthy
      control subjects (223.7 ppb). The measurement of nasal NO in our study population
      showed, below a cut-off level of < 105 ppb, a specificity of 88% for PCD, and
      positive predictive value of 89%. Nasal NO above a cut-off level of 105 ppb
      excluded PCD with a 100% certainty. The lower levels of exhaled NO in patients
      with PCD did not reach statistical significance. CONCLUSION: The measurement of
      nasal NO appears to be a useful tool to screen children for PCD and to exclude
      this disease in those with high nasal NO levels.

PMID- 15486364
TI  - Adenosine bronchial provocation with computerized wheeze detection in young
      infants with prolonged cough: correlation with long-term follow-up.
AB  - BACKGROUND: Chronic cough in babies is often associated with bronchial
      hyperreactivity (BHR). The objective documentation of BHR in babies is difficult,
      and acoustic methods have been described (provocative concentration of a
      substance causing wheeze) for conducting bronchial provocation tests (BPTs). We
      conducted a study to evaluate automatic computerized wheeze detection (CWD) in
      determining BHR in young infants with prolonged cough, and its correlation with
      the subsequent development of wheezing. METHODS: Infants aged < 24 months with
      prolonged cough (ie, > 2 months) underwent acoustic BPTs with the response
      determined by CWD and auscultation by a physician. Telephone interviews with
      parents were conducted after 1 month and yearly for the next 3 years. RESULTS: A
      total of 28 infants who were 4 to 24 months old with prolonged cough were
      included in the study. Twenty of these infants (71.4%) had BHR as determined by a
      positive acoustic BPT result. In 11 of these 20 tests, the CWD occurred earlier,
      and in 9 tests it occurred at the same step as auscultation by a physician.
      Rhonchi or whistles often preceded wheezes. Seventeen of the 20 patients with BHR
      completed 3 years of follow-up. Of these, 14 had recurrent episodes of wheezing
      and shortness of breath, and 3 were well. Six of the eight adenosine-negative
      patients completed 3 years of follow-up and had no symptoms of BHR. CONCLUSIONS:
      Acoustic BPT is a technically feasible test for the detection of BHR in young
      infants. CWD provides an earlier detection of wheeze than stethoscope
      auscultation. In our group of infants, a positive acoustic BPT result had high
      correlation with symptoms compatible with BHR over the next 3 years.

PMID- 15486365
TI  - Daily oral care and cough reflex sensitivity in elderly nursing home patients.
AB  - BACKGROUND: Intensive oral care can reduce the incidence of pneumonia in elderly
      nursing home patients, but the mechanism is unknown. OBJECTIVE: To explore the
      effects of intensive oral care on impaired cough reflex sensitivity, which is a
      known risk factor of aspiration pneumonia. METHODS: Cough reflex sensitivity to
      citric acid was measured in elderly nursing home patients, who were randomly
      assigned to the intervention group (n = 30) and the control group (n = 29). The
      patients in the intervention group had their teeth and gingiva cleaned by
      caregivers after every meal for 1 month. The patients in the control group
      performed their own oral care during the same period. Serum substance P (SP)
      concentration, cognitive function, and activities of daily living (ADL) were also
      assessed. RESULTS: In the intervention group, cough reflex sensitivity at 30 days
      showed significantly higher sensitivity than baseline (p < 0.01). At 30 days, the
      cough reflex sensitivities in the intervention group were significantly higher
      than that of the control group (p < 0.05). Compared with the control group, the
      odds ratio of improvement of cough reflex sensitivity was 5.3 (95% confidence
      interval, 1.7 to 16.0; p < 0.005) for the intervention group. One month of
      intensive oral care did not have a significant effect on serum SP concentration,
      cognitive function, and ADL. CONCLUSION: Intensive oral care may reduce the
      incidence of pneumonia by improving cough reflex sensitivity in elderly nursing
      home patients.

PMID- 15486366
TI  - Polycyclic aromatic hydrocarbons, environmental tobacco smoke, and respiratory
      symptoms in an inner-city birth cohort.
AB  - STUDY OBJECTIVES: Several studies have found associations between diesel
      exposure, respiratory symptoms, and/or impaired pulmonary function. We
      hypothesized that prenatal exposure to airborne polycyclic aromatic hydrocarbons
      (PAH), important components of diesel exhaust and other combustion sources, may
      be associated with respiratory symptoms in young children. We also hypothesized
      that exposure to environmental tobacco smoke (ETS) may worsen symptoms beyond
      that observed to be associated with PAH alone. DESIGN/PARTICIPANTS: To test our
      hypotheses, we recruited 303 pregnant women from northern Manhattan believed to
      be at high risk for exposure to both PAH and ETS, collected 48-h personal PAH
      exposure measurements, and monitored their children prospectively. RESULTS: By 12
      months of age, more cough and wheeze were reported in children exposed to
      prenatal PAH in concert with ETS postnatally (PAH x ETS interaction odds ratios
      [ORs], 1.41 [p < 0.01] and 1.29 [p < 0.05], respectively). By 24 months,
      difficulty breathing and probable asthma were reported more frequently among
      children exposed to prenatal PAH and ETS postnatally (PAH x ETS ORs, 1.54 and
      1.64, respectively [p < 0.05]). CONCLUSIONS: Our results suggest that early
      exposure to airborne PAH and ETS can lead to increased respiratory symptoms and
      probable asthma by age 12 to 24 months. Interventions to lower the risk of
      respiratory disease in young children living in the inner city may need to
      address the importance of multiple environmental exposures.

PMID- 15486367
TI  - Hospitalizations for tuberculosis in the United States in 2000: predictors of in
      hospital mortality.
AB  - STUDY OBJECTIVES: Despite curative therapy, mortality remains high for
      hospitalized patients with tuberculosis (TB) in the United States. The purpose of
      this study was to describe the characteristics of hospitalized patients with TB
      and to identify patient characteristics associated with in-hospital mortality.
      DESIGN, SETTING, AND PATIENTS: Using the 2000 Nationwide Inpatient Sample,
      representing 20% of US hospital admissions, we identified 2,279 hospital
      admissions with a primary diagnosis of TB (International Classification of
      Diseases, ninth revision, codes, 010.xx to 018.xx). MEASUREMENTS AND RESULTS:
      Mortality was the main outcome measure. Logistic regression analyses were
      performed including age, gender, race, insurance status, income, Deyo-adapted
      Charlson comorbidity index (DCI), HIV status, hospital admission source, and
      hospital characteristics as explanatory variables. A disproportionate number of
      patients hospitalized with TB were men (64%), nonwhite (72%), lived in areas with
      median incomes of < $35,000 (50%), and had publicly funded health insurance (49%)
      or no health insurance (17%). The mortality rate for patients hospitalized for TB
      was greater than that for non-TB hospital admissions (4.9% vs 2.4%, respectively;
      p < 0.001). Patients with TB who died during hospitalization were older (mean
      age, 65.1 vs 49.4 years, respectively; p < 0.001), had greater comorbid illness
      (DCI, 1.1 vs 0.55, respectively; p < 0.001), required longer hospitalizations
      (19.9 vs 13.9 days, respectively; p < 0.001), and accumulated substantially
      higher charges ($79,585 vs $31,610, respectively; p < 0.001) than did patients
      with TB who were alive at hospital discharge. In a multivariable analysis, older
      age, comorbid illnesses, and emergency department admissions were independently
      associated with mortality. The total charges for TB hospitalizations in the
      United States in 2000 exceeded $385 million. CONCLUSIONS: Despite public health
      efforts, patients who are hospitalized with TB are frequently admitted through
      emergency care settings, have a high risk of in-hospital mortality, and incur
      substantial hospital charges. To improve TB health outcomes, more vigorous
      clinical management and prevention strategies should especially target older
      patients and those with comorbid medical conditions.

PMID- 15486368
TI  - Plasma d-dimer levels correlate with outcomes in patients with community-acquired
      pneumonia.
AB  - STUDY OBJECTIVES: The aim of this study was to investigate the prognostic value
      of plasma d-dimer levels in patients with community-acquired pneumonia (CAP).
      DESIGN: Prospective observational study. SETTING: Hospital Lluis Alcanyis of
      Xativa, Spain. PATIENTS: Consecutive adult patients admitted to the hospital with
      CAP from January 2000 to October 2002. MEASUREMENTS AND RESULTS: A total of 302
      patients were included. Plasma d-dimer was measured using an automated latex
      assay. The relationships between plasma d-dimer and prognostic variables included
      in the pneumonia severity index (PSI) were examined using univariate and
      multivariate linear and logistic regression analyses. d-Dimer levels were
      negative (ie, < 500 ng/mL) in 16.9% of the patients. In nonsurvivors, the d-dimer
      plasma level mean value was 3,786 ng/mL, while in survivors it was 1,609 ng/mL (p
      < 0.0001). A significant relationship was found between the presence of elevated
      d-dimer levels and the PSI and APACHE (acute physiology and chronic health
      evaluation) II score. Elevated d-dimer levels were associated with radiologic
      pneumonia extension. The d-dimer predictive value for mechanical ventilation
      therapy showed an area under the curve of 0.78 (95% confidence interval, 0.71 to
      0.81). CONCLUSIONS: d-Dimer plasma levels could be useful for predicting clinical
      outcome in patients with CAP.

PMID- 15486369
TI  - The proportional Venn diagram of obstructive lung disease in the Italian general
      population.
AB  - STUDY OBJECTIVES: The Venn diagram of obstructive lung disease (OLD) has been
      recently quantified. We aimed to quantify the proportion of the general
      population with OLD, and the intersections of physician-diagnosed asthma, chronic
      bronchitis (CB), and emphysema in two Italian general population samples, in
      relationship to airflow obstruction (AO) determined through spirometry. DESIGN
      AND PARTICIPANTS: We analyzed data from two prospective studies (4,353 patients)
      carried out in the rural area of Po River delta from 1988 to 1991 and in the
      urban area of Pisa from 1991 to 1993. RESULTS: Prevalence rates of asthma, CB,
      and emphysema were 5.3%, 1.5%, and 1.2% in the Po delta, and 6.5%, 2.5%, and 3.6%
      in Pisa. A double Venn diagram, which was used to quantify the distribution of
      CB, emphysema, and asthma in relation to the presence/absence of AO, identified
      15 categories. Isolated AO was the most frequent category (Po delta, 11.0%; Pisa,
      6.7%), followed by asthma only without AO (Po delta, 3.3%; Pisa, 4.3%). The
      combination of the three OLD conditions was the only category that always showed
      higher prevalence rates for those with AO (Po delta, 0.20%; Pisa, 0.16%) than for
      those without AO (Po delta, 0.04%; Pisa, 0.05%). Of those with either OLD or AO,
      there were 61.4% in Po delta and 38.2% in Pisa with isolated AO, 24.8% and 41.9%,
      respectively, with an OLD without AO, and 13.8% and 19.9%, respectively, with
      simultaneous OLD and AO. For both genders, the frequency of isolated asthma
      decreased with age, while that of isolated AO, CB-emphysema, and the combination
      of asthma and CB-emphysema increased. CONCLUSION: About 18% of the Italian
      general population samples either reported the presence of OLD or showed
      spirometric signs of AO. We confirmed that the Venn diagram of OLD can be
      quantified in the general population by extending the mutually exclusive disease
      categories (including a concomitant diagnosis of asthma, CB, or emphysema) to 15.

PMID- 15486370
TI  - Mechanisms of improvement in exercise capacity using a rollator in patients with
      COPD.
AB  - STUDY OBJECTIVE: We analyzed the effects of the use of a rollator on walking
      distance and physiologic variables: pulmonary gas exchange, heart rate, minute
      ventilation (Ve), oxygen saturation, and symptoms during the 6-min walk test
      (6MWT) in patients with COPD. SETTING: Outpatient clinic at university hospital.
      PATIENTS: Fourteen patients with COPD in stable clinical condition. One patient
      had mild COPD, five patients had moderate COPD, six patients had severe COPD, and
      two patients had very severe COPD. INTERVENTIONS: Two 6MWTs were performed with a
      portable metabolic system (VmaxST 1.0; Viasys Healthcare; MEDA; Aartselaar,
      Belgium) with a rollator and without a rollator, in random order. In addition,
      maximal voluntary ventilation (MVV) was measured with and without a rollator,
      randomly. RESULTS: The median 6MWT distance increased significantly with a
      rollator: 416 m without a rollator (interquartile range [IQR], 396 to 435 m), vs
      462 m with a rollator (IQR, 424 to 477 m) [p = 0.04]. Significant increases were
      also seen in oxygen uptake (0.04 L/min [IQR, - 0.002 to 0.09 L/min]); tidal
      volume (0.06 L/min [IQR, - 0.001 to 0.11 L/min]); and Ve (0.95 L/min [IQR, - 0.67
      to 7.1 L/min]), recorded in the last minute of the 6MWT; as well as in MVV (3
      L/min [IQR, 0 to 12 L/min]) [p < 0.05 for all]. Borg dyspnea scores tended to be
      lower with a rollator: 6 (IQR, 4 to 7) without a rollator, vs 5 (IQR, 4 to 7)
      with a rollator (p = 0.10). The variation in the 6MWT was explained by individual
      changes in walking efficiency (partial R(2) = 0.31) and changes in Ve (partial
      R(2) = 0.36) [p model < 0.04]. CONCLUSION: The use of a rollator improves walking
      distance of patients with COPD through an increased ventilatory capacity and/or
      better walking efficiency.

PMID- 15486371
TI  - The effects of high-flow vs low-flow oxygen on exercise in advanced obstructive
      airways disease.
AB  - STUDY OBJECTIVES: Current options to enhance exercise performance in patients
      with COPD are limited. This study compared the effects of high flows of
      humidified oxygen to conventional low-flow oxygen (LFO) delivery at rest and
      during exercise in patients with COPD. DESIGN: Prospective, nonrandomized,
      nonblinded study. SETTING: Outpatient exercise laboratory. PATIENTS: Ten patients
      with COPD, stable with no exacerbation, and advanced airflow obstruction (age, 54
      +/- 6 years; FEV(1), 23 +/- 6% predicted [mean +/- SD]). INTERVENTIONS: After a
      period of rest and baseline recordings, patients were asked to exercise on a
      cycle ergometer for up to 12 min. Exercising was started on LFO first; after
      another period of rest, the patients repeated exercising using the high-flow
      oxygen (HFO) system, set at 20 L/min and matched to deliver the same fraction of
      inspired oxygen (Fio(2)) as that of LFO delivery. MEASUREMENTS AND RESULTS: Work
      of breathing and ventilatory parameters (tidal volume, respiratory rate,
      inspiratory time fraction, rapid shallow breathing index, pressure-time product)
      were measured and obtained from a pulmonary mechanics monitor. Borg dyspnea
      scores, pulse oximetry, blood gases, vital signs were also recorded and compared
      between the two delivery modes. Patients were able to exercise longer on high
      flows (10.0 +/- 2.4 min vs 8.2 +/- 4.3 min) with less dyspnea, better breathing
      pattern, and lower arterial pressure compared to LFO delivery. In addition,
      oxygenation was higher while receiving HFO at rest and exercise despite the
      matching of Fio(2). CONCLUSION: High flows of humidified oxygen improved exercise
      performance in patients with COPD and severe oxygen dependency, in part by
      enhancing oxygenation.

PMID- 15486372
TI  - Increased glutathione disulfide and nitrosothiols in sputum supernatant of
      patients with stable COPD.
AB  - STUDY OBJECTIVES: Increased oxidant burden is involved in the pathogenesis of
      COPD. Glutathione (GSH) is a major antioxidant scavenging reactive oxygen and
      nitrogen species. We studied the concentrations of total and reduced GSH,
      glutathione disulfide (GSSG), and nitrosothiols in sputum supernatant of patients
      with COPD. DESIGN: Twenty-five patients with moderate-to-severe COPD (FEV(1) 61
      +/- 12% of predicted) and 25 healthy nonsmoking control subjects underwent sputum
      induction. Sputum total GSH and GSSG were measured spectrophotometrically, and
      nitrosothiols were quantified by enzyme assay. Exhaled nitric oxide (eNO) was
      also measured to correlate eNO with nitrosothiols in induced sputum. MEASUREMENTS
      AND RESULTS: Compared with healthy subjects, patients with COPD had increased
      sputum neutrophils (geometric mean, 65%; 95% confidence interval [CI], 57.5 to
      71; vs 21%; 95% CI, 13.2 to 31.6; p < 0.001); total GSH (geometric mean, 7.1
      micromol/L; 95% CI, 2.95 to 17; vs 5.1 micromol/L; 95% CI, 3.2 to 8.1; p =
      0.024); GSSG (geometric mean, 4.1 micromol/L; 95% CI, 1.7 to 10; vs 0.84
      micromol/L; 95% CI, 0.35 to 1.99; p = 0.002); and nitrosothiols (geometric mean,
      60.4 micromol/L; 95% CI, 40 to 95.5; vs 38 micromol/L; 95% CI, 31.6 to 43.6; p =
      0.04). Sputum GSSG was positively correlated with neutrophils (rho = 0.47, p =
      0.016) and nitrosothiols (rho = 0.49, p = 0.024) in patients with COPD, whereas
      there was no correlation of eNO with nitrosothiols (rho = 0.38, p = 0.1).
      CONCLUSIONS: Sputum concentrations of GSSG and nitrosothiols are increased in
      patients with COPD and associated with neutrophilic inflammation. These data
      underline the role of oxidative stress in the pathogenesis of COPD, and suggest
      that GSH is important to scavenge both reactive oxygen and nitrogen species.

PMID- 15486373
TI  - Skin manifestations of inhaled corticosteroids in COPD patients: results from
      Lung Health Study II.
AB  - OBJECTIVE: To define the relationship between skin bruising (as well as other
      cutaneous manifestations) and inhaled corticosteroid (ICS) therapy vs placebo in
      subjects with COPD who were participating in a clinical trial. To explore the
      relationship between easy skin bruising and other systemic effects of ICS
      therapy, including adrenal suppression and loss of bone mineral density (BMD).
      DESIGN: Double-blind, randomized, placebo-controlled clinical trial of
      triamcinolone acetonide (1200 microg daily) vs placebo in participants with mild
      to-moderate COPD. SETTING: Lung Health Study II, a clinical trial to assess the
      effect of ICS compared to placebo in 1,116 participants in 10 centers over > 3.5
      to 4.5 years. PARTICIPANTS: A total of 1,116 smokers or recent ex-smokers with
      mild-to-moderate COPD (age range, 40 to 69 years; mean age, 56.3 years; 37.2%
      female). MEASUREMENTS AND RESULTS: Every 6 months, a structured questionnaire was
      administered to elicit reports of any bruising and/or skin rashes, slow healing
      of cuts or sores, or other skin changes. Compliance with inhaler use was assessed
      by canister weighing. A significantly higher proportion of ICS than placebo
      participants who complied with using their inhaler reported easy bruising (11.2%
      vs 3.5%, respectively) and the slow healing of skin cuts or sores (2.4% vs 0.5%,
      respectively). Older men in the ICS group with good inhaler compliance appeared
      to be at the greatest risk of bruising. In those participants undergoing serial
      measurements of adrenal function and BMD, no association was noted between skin
      bruising and either the suppression of adrenal function or the loss of BMD as
      systemic complications of ICS use. CONCLUSION: These findings indicate that
      moderate-to-high doses of ICSs result in an increased incidence of easy bruising
      and impairment in skin healing in middle-aged to elderly persons with COPD. No
      association was noted between skin bruising and other markers of systemic
      toxicity from the use of ICSs.

PMID- 15486374
TI  - How do patients determine that their metered-dose inhaler is empty?
AB  - STUDY OBJECTIVE: To evaluate how patients determined that pressurized metered
      dose inhaler (pMDI) canisters were empty and to measure pMDI depletion under
      different circumstances in the laboratory. SETTING: Most of the study was
      performed in a university research laboratory. PARTICIPANTS: Fifty consecutive
      patients attending the Brenner Children's Hospital Asthma Center were initially
      questioned regarding pMDI use, and they demonstrated their use of the inhaler.
      MEASUREMENTS AND RESULTS: Of the 50 children and parents questioned, 74% did not
      know how many actuations were in their canisters, and all used their pMDI until
      they could not longer "hear" the medication when actuating. Only half shook the
      canister before actuating. In the laboratory, chlorofluorocarbon (CFC) canisters
      typically had 86% more actuations than the nominal dose, and hydrofluoroalkane
      (HFA) canisters had 52% more. Canister flotation was ineffective in identifying
      when a pMDI was depleted, and water obstructed the valve opening 27% of the time.
      For CFC inhalers, shaking the pMDI before firing increased the number of
      actuations per canister (p = 0.009 [vs not shaking]), but this was not true for
      HFA inhalers. CONCLUSIONS: If patients are not taught to recognize when a pMDI is
      empty, they may continue to use the medication for up to twice the intended
      duration. Until accurate dose counters are added to pMDIs, counting the number of
      doses administered is the only accurate method with which to tell when the
      canister should be discarded.

PMID- 15486375
TI  - Risk factors for near-fatal asthma.
AB  - BACKGROUND: There is a paucity of lung function data in patients, both before and
      after episodes of near-fatal asthma (NFA), requiring transient endotracheal
      intubation and mechanical ventilation. METHODS: Lung function was initially
      measured in 43 asthmatic patients (age range, 16 to 49 years), who were observed
      and treated in a tertiary referral asthma clinic and were clinically stable at
      the time of study. Subsequently, clinical and physiologic follow-up studies were
      obtained over > 5 years. The primary outcomes were to determine (1) the integrity
      of lung elastic recoil and (2) the severity of expiratory airflow limitation, and
      (3) to correlate these outcomes with adverse clinical complications. RESULTS:
      Fourteen of 26 asthmatic patients (54%) [age range, 30 to 49 years] had
      significantly reduced lung elastic recoil pressures at all lung volumes compared
      to 3 of 17 asthmatic patients (18%); p = 0.02 [chi(2) test and Fisher exact test]
      [age range, 16 to 26 years]. In asthmatic patients between the ages of 30 and 49
      years, significant loss of lung elastic recoil was noted in 4 of 10 patients with
      mild reduction in FEV(1) (FEV(1), > 79% predicted), 6 of 12 patients with
      moderate reduction in FEV(1) (FEV(1), 61 to 79% predicted), and all 4 patients
      with severe reduction in FEV(1) (FEV(1), < 61% predicted). In asthmatic patients
      between the ages of 16 and 26 years, significant loss of lung elastic recoil was
      noted in 0 of 11 patients with mild reduction in FEV(1), 2 of 5 patients with
      moderate reduction in FEV(1), and 1 of 1 patient with severe reduction in FEV(1).
      A subgroup of 10 asthmatic patients (7 men) [mean (+/- SD) age, 37 +/- 11 years]
      were studied when clinically stable, both before and after an episode of NFA in 8
      cases and only after an episode of NFA in 2 additional cases. In 1 of 10 cases,
      the FEV(1) was mildly reduced, in 4 cases it was moderately reduced, and in 5
      cases it was severely reduced, both before and after an episode of NFA. The
      sensitivity was 90%, the specificity was 61%, the positive predictive value was
      41%, and the negative predictive value was 95% for NFA with an FEV(1) < or = 79%
      predicted or FEV(1)/FVC ratio of < 75%. Prior to an episode of NFA, all 8
      asthmatic patients had significant loss of lung elastic recoil pressure, and
      afterward all 10 had significant loss of lung elastic recoil pressure (ie, less
      than the predicted normal mean minus 1.64 SD at a total lung capacity [TLC] of
      100 to 70% predicted). The sensitivity was 100%, the specificity was 79%, the
      positive predictive value was 59%, and the negative predictive value was 100% for
      NFA with the loss of lung elastic recoil. The mean TLC measured with a
      plethysmograph in 10 patients with NFA was 7.2 +/- 1.41 (124 +/- 16% predicted).
      The sensitivity for TLC of > 115% predicted was 70%, the specificity was 70%, the
      positive predictive value was 88%, and the negative predictive value was 41% for
      NFA. CONCLUSION: A persistent reduction in FEV(1) of < or = 79% predicted or an
      FEV(1)/FVC ratio of < 75%, and, especially, the loss of lung elastic recoil and
      hyperinflation at TLC are risk factors for NFA. The loss of lung elastic recoil
      in asthmatic patients was associated with increased age, duration of disease, and
      progressive expiratory airflow limitation.

PMID- 15486376
TI  - Risk of physician-diagnosed asthma in the first 6 years of life.
AB  - OBJECTIVE: The objective of this cohort study was to determine if complications
      of pregnancy and labor, characteristics at birth, and exposure to infections
      influence the incidence of asthma in the first 6 years of life. DESIGN: We
      identified all children born between 1980 and 1990 in the Province of Manitoba,
      Canada. We used records of physician contacts (inpatient and outpatient) and
      services of the universal provincial health insurance plan to follow up 170,960
      children from birth to the age of 6 years to identify the first diagnosis of
      asthma. Information on mothers and siblings was also obtained to determine family
      history of disease and exposure to infections. RESULTS: During the study period,
      a diagnosis of asthma was made in 14.1% of children by the age of 6 years. The
      incidence was higher in boys than in girls, in those with family history of
      allergic diseases. It was higher in urban than in rural areas, and lowest in
      those born in winter. Asthma was more likely in those with low birth weight and
      premature birth. Certain congenital abnormalities and complications of pregnancy
      and labor also increased the risk of asthma. The risk of asthma increased with
      maternal age. Both upper and lower respiratory infections increased the risk of
      subsequent asthma, and this effect was more important than exposure to familial
      respiratory infections, which also tended to increase asthma risk. The risk of
      asthma decreased with the number of siblings when siblings had a history of
      allergic disorders. CONCLUSIONS: In addition to genetic influences, intrauterine
      and labor conditions are determinants of asthma. Exposure to both upper and lower
      respiratory tract infections increases the risk; these infections do not explain
      the protective effect associated with the increasing number of siblings.

PMID- 15486377
TI  - Effects of montelukast and salmeterol on physical performance and exercise
      economy in adult asthmatics with exercise-induced bronchoconstriction.
AB  - STUDY OBJECTIVES: To compare the effect of montelukast and the long-acting
      beta(2)-agonist salmeterol on cardiopulmonary exercise economy and physical
      performance in adult patients with asthma during exercise. DESIGN AND PATIENTS:
      Asthmatic patients (n = 18), aged 18 to 35 years with exercise-induced
      bronchoconstriction (EIB), using a double-blind, double-dummy cross-over design.
      Montelukast, 10 mg/d, was compared to inhaled salmeterol, 50 microg bid. The
      study medication was administered for at least 5 days prior to testing, with a
      washout period of at least 5 days. Treadmill exercise tests (5.3% inclination, 
      15 degrees C ambient temperature) were performed at work loads of 80% of maximal
      oxygen uptake (Vo(2)max) [6 min], rest (4 min), 60% of Vo(2)max (6 min), and
      finally step increments until exhaustion. MEASUREMENTS AND RESULTS: We
      investigated parameters of gas exchange, physical performance, and lung function.
      After montelukast, the oxygen pulse was higher than after salmeterol, at 80% of
      Vo(2)max (p = 0.035), and 6 min at 60% of Vo(2)max (p = 0.011). Lung function
      during exercise, running time to exhaustion, Borg score, lactate levels,
      Vo(2)max, carbon dioxide elimination, minute ventilation, ventilatory
      equivalents, respiratory exchange ratio, and heart rate were not significantly
      different between the two treatments. The maximal postexercise fall in FEV(1)
      from baseline occurred 2 min after run to exhaustion, and was greater after
      salmeterol than after montelukast: mean, 16.2% (SD, 11.0) vs 10.0% (SD, 12.2) [p
      < 0.001]. CONCLUSIONS: In adult asthmatics with EIB, montelukast may have a more
      favorable effect on the oxygen pulse, thus suggesting improved gas exchange
      during exercise.

PMID- 15486378
TI  - Reconcilable differences: a cross-sectional study of the relationship between
      socioeconomic status and the magnitude of short-acting beta-agonist use in
      asthma.
AB  - STUDY OBJECTIVE: To assess the association between socioeconomic status (SES) and
      short-acting (SA) beta-agonist use, controlling for asthma severity. DESIGN:
      Cross-sectional study. SETTING: Vancouver, BC, Canada. PARTICIPANTS: Two hundred
      two asthmatics between 19 years and 50 years of age and residing in the greater
      Vancouver regional district. MEASUREMENTS: The quantity of SA beta-agonist used
      in the previous year was collected by self-report; pulmonary function and beta
      receptor genotype were measured on each participant. SES was measured at both the
      individual and population levels. Five methods of adjustment for asthma severity
      were used, as follows: the Canadian Asthma Consensus Guidelines, three previously
      developed asthma-severity scores, and forward stepwise multiple regression
      modeling. Polychotomous logistic regression was used to assess all relationships.
      RESULTS: Independent of the method used to measure SES or adjust for asthma
      severity, lower SES was consistently and significantly associated with the use of
      greater amounts of SA beta-agonist. Adjusting for severity using the multivariate
      model explained the most variance of SA beta-agonist use (R(2) adjusted, 0.35 to
      0.37). In this model, social assistance recipients were more likely to use
      greater amounts of SA beta-agonist (odds ratio [OR], 3.4; 95% confidence interval
      [CI], 1.7 to 6.5). An inverse relationship between SA beta-agonist use and both
      annual household income (> $50,000; OR, 0.28; 95% CI, 0.13 to 0.60; and $20,000
      to $50,000; OR, 0.44; 95% CI, 0.21 to 0.96; relative to <$20,000) and education
      (completing a bachelor's degree vs no formal education; OR, 0.25; 95% CI, 0.14 to
      0.71). Participants living in a neighborhood with higher median household income
      (OR, 0.91; 95% CI, 0.84 to 0.98 per $1,000 increase) or a higher prevalence of
      having attained a bachelor's degree (OR, 0.96; 95% CI, 0.84 to 0.98 per 1%
      increase) were also less likely use greater amounts of SA beta-agonist. Results
      were consistent for neighborhood unemployment rate. CONCLUSIONS: The social
      gradient in asthma-related outcomes may be at least partially attributable to
      poorer asthma control in lower-SES asthmatics.

PMID- 15486379
TI  - Follow-up of adults with coarctation of the aorta: comparison of helical CT and
      MRI, and impact on assessing diameter changes.
AB  - OBJECTIVES: To compare images of the aorta obtained with helical CT (HCT)
      scanning and MRI for the follow-up of adults with coarctation of the aorta (CoA).
      DESIGN: Longitudinal study. SETTING: Department of adult congenital heart disease
      in a tertiary university hospital. PATIENTS: A total of 37 adults (age range, 16
      to 68 years; women, 13) with CoA (after surgery, 34 patients; native, 2 patients;
      after balloon-angioplasty, 1 patient) MEASUREMENTS AND RESULTS: All patients
      underwent both HCT and MRI of the thoracic aorta within a mean (+/- SD) time
      interval of 1.86 +/- 1.11 years. Aortic diameters measured at six intrathoracic
      levels showed a high correlation (r = 0.79 to 0.94). On average, slightly lower
      diameters were measured with MRI (1.2 mm). But there was a substantial variation
      between the two measurements with differences of up to 9 mm. All other
      pathomorphologic abnormalities were detected and classified similarly with both
      methods. CONCLUSIONS: HCT and MRI are similarly useful for the noninvasive
      evaluation of the thoracic aorta in patients with CoA. But there can be a
      substantial variation in two subsequent measurements without an overall
      substantial bias toward larger diameter in one of the two methods. In repetitive
      studies, changes of the diameters should be interpreted with care, especially
      when assessing the progression of aortic diameters.

PMID- 15486380
TI  - Pocket hematoma after pacemaker or implantable cardioverter defibrillator
      surgery: influence of patient morbidity, operation strategy, and perioperative
      antiplatelet/anticoagulation therapy.
AB  - STUDY OBJECTIVES: Pocket hematoma is a common complication after pacemaker or
      implantable cardioverter defibrillator (ICD) implantation. Thus, we investigated
      the influence of patient comorbidity, implantation strategy, operator experience,
      antiplatelet therapy, and anticoagulation therapy on hematoma rate. DESIGN:
      Between 1990 and 2002, a total of 3,164 devices (pectoral pacemakers, 2,792;
      ICDs, 372) were implanted at our institution. Predictors of hematoma occurrence
      were determined prospectively and were analyzed by multivariate regression
      analysis. Operator experience was graded by individual implantation number, as
      follows: low, < 50; medium, 50 to 100; and high, > 100. RESULTS: The incidence of
      pocket hematoma was 4.9%, leading to prolonged hospitalization in 2.0% of all
      patients. Reoperation for pocket hematoma was required in 1.0% of patients. High
      dose heparinization (hazard ratio [HR], 4.2), combined acetylsalicylic acid
      (ASA)/thienopyridine treatment after coronary stenting (HR, 5.2), and low
      operator experience (HR, 1.6) were independently predictive of hematoma
      development. Therapy with ASA alone did not increase the hematoma rate compared
      to patients who did receive antiplatelet or anticoagulation therapy (3.1% vs
      2.5%, respectively; difference not significant). In patients with nonvalvular
      atrial fibrillation, postoperative high-dose heparinization substantially
      increased the hematoma rate (10.7% vs 2.9%, respectively; p < 0.001) without
      reducing the rate of arterial embolism within the first month after implantation
      (0.18% vs 0.21%, respectively; difference not significant). The infection rate
      (0.28% within 3 months after implantation) was not influenced by the presence of
      the pocket hematoma. CONCLUSIONS: The use of high-dose heparinization and
      combined ASA/thienopyridine treatment are highly predictive for the occurrence of
      intraoperative bleeding and pocket hematoma in patients who have undergone
      pacemaker and ICD surgery. We propose recommendations for the management of
      antiplatelet and anticoagulation therapy in patients undergoing these
      interventions.

PMID- 15486381
TI  - Fast tracking after Ivor Lewis esophagogastrectomy.
AB  - OBJECTIVES: We streamlined our care using an algorithm for the postoperative care
      of patients who undergo Ivor Lewis esophagogastrectomy to try to reduce hospital
      stay to 7 days and maintain safety and patient satisfaction. METHODS: A
      consecutive series of 90 patients who underwent elective esophageal resection by
      one general thoracic surgeon were studied. An algorithm to guide postoperative
      care was used, featuring avoidance of the ICU, early ambulation, jejunal tube
      feeds starting on postoperative day (POD) 1, removal of nasogastric tube and
      epidural on POD 3, a gastrograffin swallow on PODs 4 or 5, and discharge on POD
      7. RESULTS: There were 90 patients (70 men). Fifty-two patients (58%) underwent
      preoperative radiation and chemotherapy. Esophagectomies were done for cancer or
      high-grade dysplasia. Forty-two of the last 55 patients (77%) went directly to
      the floor. Sixteen patients (17.7%) had major complications, which included
      pneumonia in 5 patients and aspiration pneumonia in 4 patients. There were no
      anastomotic leaks, and there were four operative deaths (4.4%). There was a
      greater incidence of failure to fast track, and to have a major complication in
      patients who underwent neoadjuvant treatment (p = 0.025 and p = 0.048,
      respectively). Median hospital stay was 7 days (range, 6 to 74 days).
      Complications or mortality could not be definitively attributed to fast tracking.
      Ninety-seven percent reported excellent satisfaction with their hospital stay,
      and four patients were readmitted within 1 month of discharge. CONCLUSIONS: Fast
      tracking patients using an algorithm after esophageal resection is safe and
      delivers minimal morbidity and mortality, and a high patient satisfaction rate. A
      median hospital stay of 7 days is possible, and the ICU can be avoided in most
      patients.

PMID- 15486382
TI  - Soluble receptor-binding cancer antigen expressed on SiSo cells in pleural fluid:
      a potential diagnostic marker for malignant pleural effusion.
AB  - BACKGROUND: We sought a marker to differentiate malignant from nonmalignant
      pleural effusions. METHODS: We studied 41 patients presenting with pleural
      effusions to the National Sanyo Hospital between April 2000 and January 2002 (33
      men and 8 women; mean age, 68 years). Twenty patients (49%) were proven to have
      malignant pleural effusions, while 21 patients (51%) had nonmalignant pleural
      effusions. Thoracentesis was performed. RESULTS: The mean (+/- SD) concentration
      of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) in malignant
      pleural effusions, measured by enzyme-linked immunosorbent assay, was
      significantly higher than that in nonmalignant pleural effusions (15.1 +/- 33.6
      vs 1.4 +/- 0.81 U/mL, respectively; p < 0.05). CONCLUSION: The determination of
      the RCAS1 concentration in pleural fluid is informative in the diagnosis of
      malignant pleural effusions.

PMID- 15486383
TI  - Hypofractionated proton beam radiotherapy for stage I lung cancer.
AB  - STUDY OBJECTIVES: To determine the efficacy and toxicity of high-dose
      hypofractionated proton beam radiotherapy for patients with clinical stage I lung
      cancer. DESIGN: A prospective phase 2 clinical trial. SETTING: Loma Linda
      University Medical Center. PATIENTS: Subjects with clinical stage I non-small
      cell lung cancer who were medically inoperable or refused surgery. INTERVENTIONS:
      All patients were treated with proton beam radiotherapy. The target included the
      gross tumor volume as seen on CT scan, with additional margin to allow for
      respiratory motion. A multibeam treatment plan was generated. Delivered treatment
      was 51 cobalt Gray equivalent (CGE) in 10 fractions over 2 weeks to the initial
      22 patients; the subsequent 46 patients received 60 CGE in 10 fractions over 2
      weeks. RESULTS: Sixty-eight patients were analyzed for this report, with a median
      follow-up time of 30 months. No cases of symptomatic radiation pneumonitis or
      late esophageal or cardiac toxicity were seen. The 3-year local control and
      disease-specific survival rates were 74%, and 72%, respectively. There was
      significant improvement in local tumor control in T1 vs T2 tumors (87% vs 49%),
      with a trend toward improved survival. Cox regression analysis revealed that
      patients with higher performance status, female gender, and smaller tumor sizes
      had significantly improved survival. CONCLUSION: High-dose hypofractionated
      proton beam radiotherapy can be administered safely, with minimal toxicity, to
      patients with stage I lung cancer. Local tumor control appears to be improved
      when compared to historical results utilizing conventional radiotherapy, with a
      good expectation of disease-specific survival 3 years following treatment.

PMID- 15486384
TI  - Strength vs aerobic training in children with cystic fibrosis: a randomized
      controlled trial.
AB  - STUDY OBJECTIVE: Exercise has the potential to improve the ability of a patient
      with cystic fibrosis (CF) to cope with the physical demands of everyday life, and
      may improve prognosis. The purpose of this study was to compare the effects of a
      home-based, semi-supervised, upper-body strength-training regimen with a
      similarly structured aerobic training regimen. DESIGN: Data were collected during
      a 1-year randomized clinical trial. SETTING: Counselors conducted in-home visits
      with the participants once per week for the first 8 weeks followed by monthly
      visits for the remainder of the study. PATIENTS: Sixty-seven patients with CF,
      aged 8 to 18 years, participated in the trial. INTERVENTION: Participants in both
      exercise conditions were encouraged to exercise at least three times per week for
      1 year. Each child in the aerobic group was given a stair-stepping machine, and
      each child in the upper-body strength training group was given an upper-body-only
      weight-resistance machine. MEASURES AND RESULTS: Aerobic fitness, pulmonary
      function, quality of life, and strength were measured at baseline, at 6 months,
      and at 12 months. Strength training increased the maximum weight lifted for
      biceps curls significantly more than aerobic training (p < 0.02). However, this
      differential did not remain significant after control for increase in height.
      Both training procedures were associated with increased strength (p < 0.002) and
      physical work capacity (PWC) [p < 0.033]. CONCLUSIONS: We concluded that strength
      and aerobic training may increase upper-body strength, and that both types of
      training may increase PWC for children with CF. Future trials should be conducted
      with no-training control subjects and larger samples to increase statistical
      power.

PMID- 15486385
TI  - Clinical manifestations of cystic fibrosis among patients with diagnosis in
      adulthood.
AB  - OBJECTIVE: To define the clinical characteristics and diagnostic parameters of
      patients with cystic fibrosis (CF) diagnosed in adulthood. DESIGN: Retrospective
      cohort study. SETTING: Tertiary care center. PATIENTS AND METHODS: All patients
      with a diagnosis of CF made at the Toronto CF Clinics between 1960 and June 2001.
      Data were collected prospectively and analyzed retrospectively. RESULTS: There
      were 73 of 1,051 patients (7%) with CF diagnosed in adulthood. Over time, an
      increasing number and proportion of patients received a diagnosis in adulthood:
      27 patients (3%) before 1990, compared to 46 patients (18%) after 1990 (p <
      0.001). The mean sweat chloride level was lower for those with CF diagnosed as
      adults, compared to those with a diagnosis as children (75 +/- 26 mmol/L and 100
      +/- 19 mmol/L, respectively; p < 0.001) [mean +/- SD], and adults were more
      likely to have pancreatic sufficiency (PS) than children (73% vs 13%,
      respectively; p < 0.0001). In 46 adults who received a diagnosis since 1990, the
      reason for the initial sweat test was pancreatitis (2 patients, 4%), pulmonary
      symptoms (18 patients, 39%), pulmonary and GI symptoms (10 patients, 22%),
      infertility (12 patients, 26%), and genetic screening (4 patients, 9%). Other
      manifestations were biliary cirrhosis (one patient) and diabetes mellitus (four
      patients, 9%). The diagnosis could be confirmed by sweat test alone in 30 of 46
      patients (65%), by mutation analysis alone in 15 patients (33%), and by a
      combination in 31 patients (67%). Nasal potential difference (PD) measurements
      alone confirmed the diagnosis in the remaining 15 patients (33%). CONCLUSION:
      Patients with CF presenting in adulthood often have PS, inconclusive sweat test
      results, and a high prevalence of mutations that are not commonly seen in CF
      diagnosed in childhood. Although most patients have lung disease of variable
      degrees, single-organ manifestations such as congenital bilateral absence of the
      vas deferens and pancreatitis are seen. Repeated sweat tests and extensive
      mutation analysis are often required. Nasal PD may aid the diagnosis, but has not
      been standardized for clinical diagnosis.

PMID- 15486386
TI  - Reference values for pulmonary function in Asian Indians living in the United
      States.
AB  - OBJECTIVE: To establish reference values for pulmonary function in the Asian
      Indian population living in the United States. DESIGN: Five-year cross-sectional
      study of pulmonary function in healthy adult Asian Indians living in the United
      States, using American Thoracic Society guidelines for measuring pulmonary
      function. SETTING: Measurement of pulmonary function in healthy nonsmoking Asian
      Indians in a pulmonary function laboratory or at festivals, picnics, and
      ceremonies where subjects could be conveniently recruited. PARTICIPANTS: Four
      hundred sixty subjects from a population of Asian Indians residing in the Chicago
      metropolitan area. MEASUREMENTS: Spirometry was performed in all subjects with
      measurements of FEV(1), FVC, and forced expiratory flow between 25% and 75% of
      vital capacity (FEF(25-75)). Lung volumes were measured in eighty subjects.
      Prediction equations for FEV(1), FVC, and FEF(25-75) were derived using multiple
      regression analysis. RESULTS: Three hundred sixty-three subjects (226 men and 137
      women) met the inclusion criteria. Spirometric values derived from our prediction
      equations, when compared to the values for whites from the selected studies in
      the literature, showed FVC to be 20 to 24% lower in men and 25 to 28% lower in
      women. FEV(1) was 16 to 23% lower in men and 20 to 26% lower in women.
      Differences were not quite as large when compared to values from African
      Americans and other studies on Asians. CONCLUSIONS: We provide reference values
      for pulmonary function in nonsmoking Asian Indians living in the United States.
      These reference values should be used for evaluation of pulmonary function in
      this population.

PMID- 15486387
TI  - Respiratory symptoms and undiagnosed airflow obstruction in middle-aged adults:
      the Korean Health and Genome Study.
AB  - BACKGROUND: The prevalence of undiagnosed airflow obstruction is difficult to
      measure since it requires screening in population-based samples to identify
      individuals free of clinical symptoms. The purpose of this report is to examine
      the prevalence of undiagnosed airflow obstruction and its relation with
      respiratory symptoms in middle-age adults in the Korean Health and Genome (KHG)
      Study. METHODS: The KHG study is an ongoing population-based study of Korean
      adults aged 40 to 69 years. The current report includes 8,140 men and women
      without a pulmonary disorder or obstructive lung disease. In this sample,
      undiagnosed airflow obstruction was defined on the basis of spirometric testing
      and in the absence of a medical history or a recognized pulmonary disorder.
      Respiratory symptoms included chronic cough, chronic phlegm, wheezing, and
      shortness of breath. RESULTS: Undiagnosed airflow obstruction was observed in
      12.4% of the men (470 of 3,806 subjects) and in 3.5% of the women (152 of 4,334
      subjects). In men, the age-adjusted prevalence of undiagnosed airflow obstruction
      increased consistently with increasing number of respiratory symptoms. In those
      who smoked, there was a 2.3-fold excess in its prevalence when three or more
      symptoms were present, as compared to when they were absent (27.4% vs 12.0%, p <
      0.001). A 2.4-fold excess (20.6% vs 8.5%, p = 0.004) was observed in nonsmoking
      men, in whom respiratory symptoms were consistently less common than in those who
      smoked. Respiratory symptoms were unrelated to undiagnosed airflow obstruction in
      women smokers, although only 3.9% smoked cigarettes. In women who were
      nonsmokers, the prevalence of undiagnosed airflow obstruction increased from 2.3%
      in those without a respiratory symptom to 6.0% when three or more symptoms were
      present (p = 0.003). CONCLUSIONS: Findings suggest that undiagnosed airflow
      obstruction is common in Korea with several respiratory symptoms. Whether
      respiratory symptoms with associations with undiagnosed airflow obstruction can
      be used to design early intervention strategies that prevent or delay the onset
      of COPD and its disabling consequences warrants further study.

PMID- 15486388
TI  - Predictive factors of quality-of-life improvement and continuous positive airway
      pressure use in patients with sleep apnea-hypopnea syndrome: study at 1 year.
AB  - STUDY OBJECTIVES: To assess predictive factors of quality-of-life (QoL)
      improvement and continuous positive airway pressure (CPAP) use in patients with
      sleep apnea-hypopnea syndrome (SAHS) after 1 year of treatment with CPAP. DESIGN:
      Observational, prospective cohort study. SETTING: Sleep unit in a university
      hospital. PATIENTS: One hundred thirty-three consecutive patients with an
      indication for CPAP treatment. MEASUREMENTS AND RESULTS: Nottingham health
      profile (NHP) questionnaire, Epworth sleepiness scale score, and objective CPAP
      use (time counter in the CPAP device) were assessed at baseline and after 3
      months and 12 months of CPAP use. Multivariate logistic regression was used to
      identify predictive factors of CPAP use and improved QoL. At 1 year, 101 patients
      (76%) were still using CPAP; of these, 88 patients (66%) completed all the follow
      up questionnaires. QoL was lower before treatment, compared with the general
      population, and all dimensions of the NHP, except social isolation, improved
      significantly from baseline in patients regularly using CPAP, reaching levels
      comparable to those of the general population at 1 year. Only minimum
      oxyhemoglobin saturation at diagnostic polysomnography was associated with the
      degree of QoL improvement at 1 year. Only the NHP and the apnea-hypopnea index
      (AHI) at baseline were significantly associated with hours of CPAP use at 1 year.
      CONCLUSIONS: Compared to the general population, patients with untreated SAHS had
      a lower QoL, which improved to the level of the general population after 3 months
      of CPAP therapy and persisted at 1 year of treatment with CPAP. The only
      predictor of QoL improvement was minimum nocturnal oxygen saturation at baseline.
      Higher AHI and worse QoL at baseline were predictors of hours of CPAP use.

PMID- 15486389
TI  - Mouth breathing compromises adherence to nasal continuous positive airway
      pressure therapy.
AB  - STUDY OBJECTIVES: Mouth leak compromises nasal continuous positive airway
      pressure (CPAP) therapy. We hypothesized that patients who breathe mainly through
      their mouths during sleep, compared to those who breathe mainly through their
      noses, would have more mouth leak during CPAP and therefore lower adherence to
      CPAP. DESIGN: A case-control study to compare adherence to CPAP at 1 year in
      mouth breathers (MBs) with nose breathers (NBs). SETTING: University teaching
      hospital with a sleep laboratory. PATIENTS: Fifty-one CPAP-naive patients (4
      women), with a respiratory disturbance index (RDI) > 15/h. Of the 51 patients, 30
      patients breathed through their mouths (mouth breathing > 70% of total sleep time
      [TST]), and 21 patients breathed through their noses (mouth breathing < 30% of
      TST). MBs between 30% and 70% of TST were excluded. INTERVENTIONS: Overnight
      polysomnography was performed at baseline, during CPAP titration, and at 3
      months. Patients were followed up for 1 year after beginning CPAP. MEASUREMENTS
      AND RESULTS: To measure mouth breathing, nasal and oral thermistors during
      polysomnography were separated by a 3 x 6-cm silicon transverse diaphragm. RDI
      decreased from (mean +/- SD) 37.8 +/- 21.5 to 1.8 +/- 2.6/h at 3 months.
      Throughout the study, adherence to CPAP (mean daily CPAP use in hours) was better
      in NBs. Most NBs (71%) but only 30% of MBs used CPAP daily for > 4 h at 1-year
      follow-up. Mouth breathing decreased significantly from 84 +/- 8.9% at baseline
      to 22 +/- 14.4% at 3 months. CONCLUSION: Patients with moderate-to-severe sleep
      disordered breathing and a high percentage of mouth breathing during sleep were
      less adherent to CPAP therapy than patients exhibiting a low percentage of mouth
      breathing.

PMID- 15486390
TI  - Elevated basic fibroblast growth factor levels in patients with pulmonary
      arterial hypertension.
AB  - STUDY OBJECTIVES: Cellular growth in the vascular wall, including endothelial and
      smooth-muscle cell proliferation, is recognized as a component of the obstructive
      vasculopathy observed in the small vessels of the lungs in pulmonary arterial
      hypertension (PAH). We hypothesized that angiogenic growth factors may have a
      role in the molecular mechanisms underlying this cellular proliferation. DESIGN:
      Case-control study. SETTING: Multicenter, tertiary care hospitals. PARTICIPANTS:
      We studied 117 patients with PAH and 60 control subjects. MEASUREMENTS: We
      measured levels of basic fibroblast growth factor (bFGF) and vascular endothelial
      growth factor (VEGF) in the blood and urine of these subjects using an enzyme
      linked immunoassay. RESULTS: Median levels of urinary and plasma bFGF were
      significantly higher in patients with PAH compared to normal control subjects.
      There was a difference in levels of urine and plasma bFGF according to etiology
      of pulmonary hypertension, with the highest levels seen in patients with primary
      pulmonary hypertension. Levels of urine or plasma VEGF were not significantly
      different between patients and control subjects. CONCLUSION: Patients with PAH
      have substantial alterations in urine and plasma levels of bFGF. This molecule
      may have a role as a mitogenic factor in the endothelial and smooth-muscle cell
      proliferation seen in PAH.

PMID- 15486391
TI  - Impact of evacuated collection tube fill volume and mixing on routine coagulation
      testing using 2.5-ml (pediatric) tubes.
AB  - BACKGROUND: Anecdotal observations by pharmacists monitoring anticoagulated
      patients indicate that blood samples collected in 2.7-mL (pediatric) evacuated
      tubes frequently produced falsely elevated international normalized ratio (INR)
      results. OBJECTIVE: To evaluate the impact of various preanalytical variables
      (fill volume, sample mixing, and elapsed time between sample collection and
      mixing) on INR test results using pediatric collection tubes in healthy
      volunteers and patients receiving warfarin anticoagulation therapy. Fifteen
      patients receiving warfarin and the 15 healthy volunteers participated in each
      study arm. METHODS: Multiple blood samples for coagulation testing were obtained
      from study subjects in full-draw pediatric collection tubes made of siliconized
      glass. The impact of sample mixing was evaluated by randomly varying the number
      of times each tube (five tubes total) was inverted following sample collection
      between one and five. The impact of timely sample mixing was evaluated by
      randomly varying the elapsed time between sample collection and mixing between 0
      min and 4 min in each of five samples. The impact of incomplete collection tube
      filling was evaluated by randomly varying the volume of six tubes between 50% and
      100%. Duplicate coagulation assays were performed on each sample by a centralized
      hematology laboratory, and the average result was reported. RESULTS: Statistical
      analysis revealed that neither sample mixing nor the elapsed time between sample
      collection and mixing had a statistically significant effect on INR test results.
      For patients receiving warfarin, tube fill volume had a statistically significant
      effect on the reported INR results (p < 0.001). The mean (+/- SD) INR derived
      from sample tubes filled 100% was 3.2 +/- 1.2, compared to 9.9 +/- 4.2 for tubes
      filled only 50% full (p < 0.01). Statistically significant INR elevations became
      apparent for sample tube fill volumes of < 90%. CONCLUSION: Pediatric blood
      collection tubes should be filled at least 90% full to ensure accurate INR test
      results. Anticoagulation therapy providers should routinely inquire about the
      type of collection tube used (adult vs pediatric) and the adequacy of sample
      collection volume before deriving therapeutic plans in asymptomatic excessively
      anticoagulated patients.

PMID- 15486392
TI  - A prospective randomized comparison of train-of-four monitoring and clinical
      assessment during continuous ICU cisatracurium paralysis.
AB  - STUDY PURPOSE: Train-of-four (TOF) monitoring is often recommended during the
      continuous use of neuromuscular blockade (NMB) [paralysis] in the ICU. Prior
      study results are conflicting regarding the benefits of TOF monitoring. DESIGN:
      Thirty patients in the medical ICU were randomized to TOF monitoring (n = 16) or
      to clinical assessment (n = 14) during continuous cisatracurium infusion. TOF
      monitoring was done at least every 4 h, with the goal being maintenance of one to
      two twitches. Statistical analysis was performed by two-tailed, unpaired t test
      (with Bonferroni correction for multiple comparisons), chi(2), and Fisher exact
      test, with p < 0.05 considered significant. Given a power of 80%, and the
      variance seen in the two groups, we estimate that the sample size used is
      sufficient to detect a change of > or = 60 min between groups for recovery time.
      RESULTS: The mean recovery time after cessation of paralytics was no different
      between TOF and clinical assessment (45 +/- 7 min vs 38 +/- 10 min, respectively
      [mean +/- SEM]). No differences were noted for mean APACHE (acute physiology and
      chronic health evaluation) II entry scores, glomerular filtration rates, or use
      of corticosteroids. No significant differences were noted between TOF monitoring
      and clinical assessment in mean total paralysis time (4,118 +/- 1,012 min vs
      3,188 +/- 705 min, respectively), mean total cisatracurium dose (920 +/- 325 mg
      vs 715 +/- 167 mg), or dosage (2.3 +/- 0.2 microg/kg/min vs 2.9 +/- 0.2
      microg/kg/min). CONCLUSIONS: TOF monitoring does not lead to improved recovery
      time or lower cisatracurium dosing compared with monitoring by clinical
      assessment. We conclude that TOF monitoring is unnecessary, and careful titration
      of the neuromuscular blocking agent by clinical assessment alone is sufficient in
      patients undergoing continuous cisatracurium NMB.

PMID- 15486393
TI  - Pleural effusions in febrile medical ICU patients: chest ultrasound study.
AB  - STUDY OBJECTIVES: To assess the necessity of thoracentesis in febrile medical ICU
      (MICU) patients, and to evaluate the efficiency and reliability of sonographic
      effusion patterns for diagnosing empyema. DESIGN AND SETTING: A prospective, 1
      year, tertiary-care hospital study of febrile MICU patients with physical,
      radiographic, and ultrasonographic evidence of pleural effusion. PATIENTS: During
      this study period, we screened 1,640 patients who had been admitted to the MICU;
      of these, 94 patients had a temperature > 38 degrees C for > 8 h with evidence of
      pleural effusion proven by chest radiography and ultrasound. INTERVENTION:
      Routine thoracentesis and pleural effusion cultures were performed in 94 febrile
      patients under portable chest ultrasound guidance. Three days later, if the first
      pleural effusion culture was inconclusive and the patient still had persistent
      fever of > 38 degrees C, we repeated the diagnostic thoracentesis and pleural
      effusion culture. In total, 118 procedures were performed in those 94 febrile
      patients. MEASUREMENTS AND RESULTS: In all, 58 patients (62%) had infectious
      exudates (parapneumonic, n = 36; empyema, n = 15; urosepsis, n = 3; liver
      abscess, n = 2; deep neck infection, n = 1; and wound infection, n = 1), 28
      patients (30%) had transudates, and 8 patients (8%) had noninfectious exudates.
      The prevalence of empyema in febrile patients admitted to the MICU was 16% (15 of
      94 patients). Analyses of the sonographic patterns of the 15 patients with
      empyema out of the 118 thoracenteses performed showed the following: anechoic
      pattern, 0% (0 of 47 procedures); complex nonseptated and relatively
      nonhyperechoic pattern, 0% (0 of 36 procedures); complex nonseptated and
      relatively hyperechoic pattern, 100% (2 of 2 procedures); complex septated
      pattern, 35% (11 of 31 procedures); and homogeneously echogenic pattern, 100% (2
      of 2 procedures). Hemothorax was the only complication, and it occurred in two
      patients (2%). Both patients had a favorable outcome after drainage. CONCLUSION:
      Portable chest ultrasound examination and ultrasound-guided thoracentesis in
      febrile MICU patients are safe, feasible, and useful methods for diagnosing
      thoracic empyema. Our results suggest that only some sonographic patterns of
      pleural effusion (homogeneously echogenic, complex nonseptated and relatively
      hyperechoic, and complex septated) deserve aggressive assessment and rapid
      management.

PMID- 15486394
TI  - Changing pattern of ventilator settings in patients without acute lung injury:
      changes over 11 years in a single institution.
AB  - STUDY OBJECTIVES: To determine whether the widely accepted concept of using lower
      tidal volume (Vt) values in patients with ARDS or obstructive lung disease has
      affected the pattern of ventilator settings in mechanically ventilated patients
      who do not have one of these conditions. DESIGN AND PATIENTS: We performed a
      retrospective chart review of all patients who had experienced out-of-hospital
      cardiac arrest and had received ventilatory support for > or = 1 day at a
      university-affiliated county hospital during the years 1990, 1991, 1992, 1995,
      1998, 1999, and 2000. RESULTS: In 139 such patients, the mean final Vt values
      used on the first day of mechanical ventilation were 11.7, 12.4, 11.3, 9.6, 9.7,
      9.2, and 9.8 mL/kg in those years, respectively. Multivariate analysis revealed
      that increasing year (beta-coefficient = -0.24; p = 0.001) and the presence of
      pulmonary edema (beta-coefficient = -1.2; p = 0.001) were independent predictors
      of the use of lower Vt values. Patients managed with a low Vt (ie, < 10 mL/kg;
      mean [+/- SD] Vt, 8.4 +/- 1.3 mL/kg) had a significantly higher incidence of
      atelectasis than the patients who were managed with traditional, larger Vt values
      (ie, > or = 10 mL/kg; mean Vt, 11.8 +/- 1.5 mL/kg) [61.1% vs 36.7%, respectively;
      p = 0.02]. Multivariate analysis revealed that the mean Vt used on days 1, 2, and
      3 (<10 mL/kg or > or = 10 mL/kg) was the only predictor of the development of
      atelectasis during the first 3 days of mechanical ventilation (odds ratio, 0.33;
      p = 0.015). There was no difference in the incidence of pneumonia, the number of
      days spent receiving mechanical ventilation, Pao(2)/fraction of inspired oxygen
      ratio, or respiratory system compliance between the low Vt group and the
      traditional Vt group. CONCLUSION: Currently, physicians at our hospital use lower
      Vt values than they have in the past. This is associated with the increase in the
      incidence of atelectasis in the patients who received ventilation using low Vt
      values.

PMID- 15486395
TI  - The hospital mortality of patients admitted to the ICU on weekends.
AB  - STUDY OBJECTIVES: Previous studies have suggested that patients are more likely
      to die in the hospital if they are admitted on a weekend than on a weekday. This
      study was conducted to determine whether weekend admission to the ICU increases
      the risk of dying in the hospital. DESIGN: Retrospective cohort study. SETTING:
      ICU of a single tertiary care medical center. PATIENTS: A total of 29,084
      patients admitted to medical, surgical, and multispecialty ICUs from October 1994
      through September 2002. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The
      weekend ICU admissions comprised 27.9% of all ICU admissions (8,108 ICU
      admissions). The overall hospital mortality rate was 8.2% (2,385 deaths). Weekend
      ICU admission was associated with a higher unadjusted hospital mortality rate
      than that for weekday ICU admission (11.3% vs 7.0%, respectively; odds ratio
      [OR], 1.70; 95% confidence interval [CI], 1.55 to 1.85). In multivariable
      analyses controlling for the factors associated with mortality such as APACHE
      (acute physiology and chronic health evaluation) III predicted mortality rate,
      ICU admission source, and intensity of treatment, no statistically significant
      difference in hospital mortality was found between weekend and weekday admissions
      in the overall study population (OR, 1.06; 95% CI, 0.95 to 1.17). For weekend ICU
      admissions, the observed hospital mortality rates of the medical, multispecialty,
      and surgical ICUs were 15.2%, 17.2%, and 6.4%, respectively, and for weekday ICU
      admissions the rates were 16.3%, 10.1%, and 3.5%, respectively. Subgroup analyses
      showed that weekend ICU admission was associated with higher adjusted hospital
      mortality rates than was weekday ICU admission in the surgical ICU (OR, 1.23; 95%
      CI, 1.03 to 1.48), but not in the medical or multispecialty ICUs. CONCLUSIONS:
      The overall adjusted hospital mortality rate of patients admitted to the ICU on a
      weekend was not higher than that of patients admitted on a weekday. However,
      weekend ICU admission to the surgical ICU was associated with an increased
      hospital mortality rate.

PMID- 15486396
TI  - Outcome in noninvasively and invasively ventilated hematologic patients with
      acute respiratory failure.
AB  - STUDY OBJECTIVES: The survival rate of patients with a hematologic malignancy
      requiring mechanical ventilation (MV) in the ICU has improved over the last few
      decades. The objective of this study was to identify the factors affecting the in
      hospital mortality of these particular patients, and to assess whether the use of
      noninvasive positive pressure ventilation (NPPV) was protective in our study
      population. DESIGN: We retrospectively collected variables in 166 consecutive
      patients with hematologic malignancies who had acute respiratory failure (ARF)
      requiring MV, and identified factors obtained within 24 h of ICU admission
      affecting in-hospital mortality in univariate and multivariate stepwise logistic
      regression analyses. The effect of NPPV on mortality was assessed using a pair
      wise matched exposed-unexposed analysis. RESULTS: The mean simplified acute
      physiology score (SAPS) II was 58.9. The in-hospital mortality rate was 71%. In a
      multivariate logistic regression analysis, the in-hospital mortality rate was
      predicted by increasing severity of illness, as measured by SAPS II (odds ratio
      [OR] per point of increase, 1.07; 95% confidence interval [CI], 1.04 to 1.11) and
      a diagnosis of acute myelogenous leukemia (OR, 2.73; 95% CI, 1.05 to 7.11).
      Female sex (OR, 0.36; 95% CI, 0.16 to 0.82), endotracheal intubation (ETI) within
      24 h of ICU admission (OR, 0.29; 95% CI, 0.11 to 0.78), and recent bacteremia
      (defined as blood cultures positive for bacteria < 48h before or < 24h after ICU
      admission) [OR, 0.22; 95% CI, 0.08 to 0.61] were associated with a lower
      mortality rate. Twenty-seven patients who received NPPV were matched for SAPS II
      (+/- 3) with 52 patients who required immediate ETI on a 1:2 basis. The crude in
      hospital mortality rate was 65.4% in both groups. CONCLUSION: Although the in
      hospital mortality rate in hematologic patients who develop ARF remains high, the
      reluctance to intubate and start treatment with invasive MV in this population is
      unjustified, especially when bacteremia has precipitated ICU admission.

PMID- 15486397
TI  - Hypothyroidism and failure to wean in patients receiving prolonged mechanical
      ventilation at a regional weaning center.
AB  - OBJECTIVE: Hypothyroidism is cited as an uncommon cause of ventilator-dependent
      respiratory failure. The objective of this study was to determine the incidence
      of hypothyroidism in patients with respiratory failure, receiving prolonged
      mechanical ventilation (PMV) with failure to wean, referred to a regional weaning
      center (RWC) for weaning. SETTING: RWC. DESIGN: Retrospective. METHODS: Medical
      records were reviewed of 173 patients admitted to this RWC between January 1999
      and March 2002. One hundred forty patients were noted to have had screening serum
      thyroid stimulating hormone (TSH) levels obtained at admission. Records of these
      patients were further evaluated. The following data were abstracted: age, sex,
      body mass index, serum TSH levels, number of patients with previously diagnosed
      hypothyroidism, and number of patients with hypothyroidism diagnosed clinically
      and by laboratory tests following admission to the RWC. Primary outcome was
      liberation from PMV, which was defined as being off ventilatory support for > 1
      week. Univariate analysis was performed to determine relation between serum TSH
      levels and outcome; p < 0.05 was deemed statistically significant. RESULTS: Of
      140 patients studied, 67 were male (48%) and 73 were female (52%), with a mean
      age of 66 + 15 years (+/- SD). Only one patient had a history of previously
      diagnosed hypothyroidism. A clinical diagnosis of hypothyroidism was made in 4 of
      140 patients (3%) following admission. Serum TSH levels ranged from 0.19 to 121
      mU/L in the studied subjects. Seventeen of 140 patients (12%) had elevated serum
      TSH levels. Serum tri-iodothyronine and/or thyroxine levels confirmed diagnosis
      of hypothyroidism in four of these patients (3%). Patients with newly diagnosed
      hypothyroidism were treated with thyroid supplements, and three patients were
      liberated from PMV while one patient died from other medical causes. Of the 140
      patients, 92 patients (67%) were liberated from PMV while 48 patients (33%) could
      not be weaned. Mean serum TSH levels were 4.2 + 13 mU/L in the liberated patients
      and 4 + 4.7 mU/L in the patients who could not be weaned (p = 0.25). CONCLUSION:
      Hypothyroidism is an uncommon cause of failure to wean in patients receiving PMV
      (with an incidence of 3%). However, it is a potentially treatable cause and
      should be considered in all patients who fail to wean. Serum TSH level does not
      appear to affect successful weaning from PMV.

PMID- 15486398
TI  - New formula for predicting mean pulmonary artery pressure using systolic
      pulmonary artery pressure.
AB  - STUDY OBJECTIVES: Mean pulmonary artery pressure (MPAP) and systolic pulmonary
      artery pressure (SPAP) are used interchangeably to define pulmonary hypertension
      (PH). We tested the hypothesis that the measurement of MPAP and SPAP is redundant
      in resting humans over a wide pressure range. DESIGN: Prospective, observational
      study. SETTING: Catheterization laboratory in a university hospital. PATIENTS:
      This study involved 31 patients, as follows: primary PH, nine patients; chronic
      pulmonary thromboembolism, seven patients; venous PH, six patients; and control
      subjects with normal pulmonary artery pressure, nine patients. INTERVENTIONS:
      None. MEASUREMENTS AND RESULTS: High-fidelity pulmonary artery pressures were
      obtained when patients were at rest. Over the wide MPAP range that was under
      study (10 to 78 mm Hg), MPAP and SPAP were strongly related (r(2) = 0.98).
      Regression analysis performed on the first 16 subjects (test sample) allowed us
      to propose a formula (MPAP = 0.61 SPAP + 2 mm Hg), the accuracy of which was
      confirmed in the remaining 15 subjects (validation sample bias, 0 +/- 2 mm Hg).
      If PH was defined by an SPAP in excess of 30 or 40 mm Hg, this corresponded to an
      MPAP in excess of 20 or 26 mm Hg. If PH was defined by an MPAP of > 25 mm Hg,
      this corresponded to an SPAP of > 38 mm Hg. CONCLUSIONS: In resting humans, MPAP
      can be accurately predicted from SPAP over a wide pressure range. The new formula
      may help to refine the threshold pressure values used in the diagnosis of PH.
      Further studies are needed to test the hypothesis that our formula may allow the
      noninvasive prediction of MPAP from Doppler-derived SPAP values.

PMID- 15486399
TI  - Malignant pleural mesothelioma: update, current management, and newer therapeutic
      strategies.
AB  - The diagnosis and management of malignant pleural mesothelioma are major
      challenges that often frustrate both patient and clinician alike. Occupational
      asbestos exposure to crocidolite or amosite forms of the fiber is the most
      important known risk factor in North America and Western Europe. Other mineral
      fibers such as erionite, a naturally occurring fibrous zeolite crystal, are
      associated with mesothelioma in volcanic tuffs of the Cappadocia region of
      central Anatolia in Turkey. In addition, other possible factors such as the
      presence of simian virus 40 and genetic susceptibility have been associated
      recently with the development of mesothelioma in animal models. These latter
      findings are increasing our understanding of this disease. In addition, the
      discovery of elevated levels of various markers such as folic acid receptor
      alpha, cyclooxygenase 2, and multidrug resistance proteins 1 and 2 in
      mesothelioma tissue have opened up new areas of potential diagnostic and
      therapeutic importance. However, traditional treatment modalities--surgery,
      radiotherapy, and chemotherapy--have evolved slowly, and few gains in therapeutic
      efficacy have occurred. Recently, however, continuing research efforts have led
      to novel treatment strategies that are changing the way clinicians view a disease
      that has traditionally been managed with almost universal therapeutic nihilism.
      This review explores our current knowledge of this disease and presents current
      and novel therapeutic strategies.

PMID- 15486400
TI  - Natriuretic peptides, respiratory disease, and the right heart.
AB  - It is well-recognized that atrial natriuretic peptide (ANP) and B-type
      natriuretic peptide (BNP) are raised in conditions with ventricular volume and
      pressure overload. In addition to this established role in left ventricular
      congestive cardiac failure, there is good evidence that BNP has a diagnostic role
      in right ventricular (RV) dysfunction and pulmonary arterial hypertension (PAH).
      For example, BNP levels can be used to differentiate between dyspneic patients
      with pure respiratory defects and those with RV dysfunction. Studies in patients
      with PAH have demonstrated significant correlations between BNP levels and mean
      pulmonary arterial pressure as well as pulmonary vascular resistance.
      Additionally, BNP has a prognostic role in patients with RV pressure overload and
      pulmonary hypertension, and it offers a noninvasive test that can be used to
      guide therapy in patients with PAH. However, although measured plasma proBNP
      levels are raised in conditions with RV overload, its biological significance is
      still not well-understood. In this article, we review the general physiologic and
      potential therapeutic role of natriuretic peptides in respiratory disease, RV
      dysfunction, and PAH. Furthermore, we assess the various clues toward natriuretic
      peptide action coming from laboratory studies. ANP and BNP knockout mice develop
      cardiac fibrosis and hypertrophy. Potentiation of the natriuretic pathway has
      been shown to reduce cardiac hypertrophy and PAH. This is likely to take place as
      a result of increased intracellular cyclic guanosine monophosphate levels and
      subsequent pulmonary vasorelaxant activity. In view of this evidence, there may
      be a rationale for the therapeutic use of recombinant BNP or neutral
      endopeptidase inhibitors under conditions of RV dysfunction and PAH.

PMID- 15486401
TI  - Depreotide scanning in sarcoidosis: a pilot study.
AB  - STUDY OBJECTIVES: To determine whether sarcoidosis results in uptake on (99m)Tc
      labeled depreotide (DP) scintigraphy and to generate preliminary data to guide
      the development of future trials exploring this imaging modality in sarcoidosis
      patients. DESIGN: Prospective cohort trial among a convenience sample of patients
      with sarcoidosis. SETTING: Tertiary care medical center pulmonary clinic.
      PATIENTS: Subjects in whom sarcoidosis has been diagnosed based on a biopsy
      revealing nonnecrotizing granulomas. INTERVENTIONS: Two hours after IV
      administration of (99m)Tc-DP, all patients underwent whole-body anterior and
      posterior planar imaging, followed by thoracic single-photon emission CT
      scanning. Images were interpreted by two nuclear medicine physicians who were
      blinded to the patient's clinical status. MEASUREMENTS AND RESULTS: The study
      cohort included 22 subjects (mean [+/- SD] age, 41.3 +/- 9.3 years; 40% female).
      Approximately half of the cohort had stage I disease determined by chest
      radiographs (CXRs). The results of (99m)Tc-DP scintigraphy were positive for
      sarcoidosis in 18 individuals (81.8%; 95% confidence interval, 59.7 to 94.8%). Of
      the four persons lacking (99m)Tc-DP uptake, all had normalized their CXRs since
      the time of presentation. In the entire sample, the intraclass correlation
      between radiographic stage determined by CXR vs that determined by (99m)Tc-DP
      scintigraphy was robust (kappa = 0.79; p = 0.0005). Among patients with positive
      (99m)Tc-DP scan findings, the correlation was stronger (kappa = 0.94; p <
      0.0001). Flow rates and lung volumes were lower in patients with parenchymal
      activity on (99m)Tc-DP scintigraphy (mean FEV(1), 68.6 +/- 13.9% predicted vs
      84.5 +/- 10.7% predicted, respectively [p = 0.012]; mean FVC, 74.0 +/- 16.0%
      predicted vs 88.4 +/- 12.7% predicted [p = 0.041]). (99m)Tc-DP scintigraphy
      correctly identified all sites of known nonpulmonary visceral involvement with
      sarcoidosis. CONCLUSIONS: The results of (99m)Tc-DP imaging are often positive in
      sarcoidosis patients, and correlate with disease stage determined by CXR and
      pulmonary function. (99m)Tc-DP scintigraphy does not preclude the need for biopsy
      if this is indicated to confirm the diagnosis of sarcoidosis or to exclude the
      possibility of malignancy. (99m)Tc-DP scintigraphy merits further study in the
      evaluation and management of sarcoidosis.

PMID- 15486402
TI  - Interventional bronchoscopy in the management of airway stenosis due to
      tracheobronchial tuberculosis.
AB  - STUDY OBJECTIVES: To assess the efficacy and complications of interventional
      bronchoscopic techniques in treating airway stenosis due to tracheobronchial
      tuberculosis. DESIGN: Case series. SETTING: Respiratory care centers at two
      tertiary care referral teaching hospitals in Japan, Hiroshima City Hospital and
      Okayama Red Cross Hospital. PATIENTS AND INTERVENTIONS: A total of 30 patients
      were admitted to the hospital with a diagnosis of tracheobronchial tuberculosis
      between January 1991 and January 2002. Of those 11 patients received
      interventional bronchoscopy, including stent placement, laser photoresection,
      argon plasma coagulation (APC), balloon dilatation, cryotherapy, and
      endobronchial ultrasonography (EBUS). One patient with complete bronchial
      obstruction underwent a left pneumonectomy. RESULTS: Six patients underwent stent
      placement after balloon dilatation, while the remaining five patients underwent
      only balloon dilatation. In six patients, Dumon stents were successfully placed
      to reestablish the patency of the central airways. Two patients first had
      Ultraflex stents implanted but had problems with granulation tissue formation and
      stent deterioration caused by metal fatigue due to chronic coughing. Dumon stents
      then were placed within the Ultraflex stents after the patient had received
      treatment with APC and mechanical reaming using the bevel of a rigid
      bronchoscope. In four patients, EBUS images demonstrated the destruction of
      bronchial cartilage or the thickening of the bronchial wall. The main
      complications of Dumon stents are migration and granulation tissue formation,
      necessitating stent removal, or replacement, and the application of cryotherapy
      to the granuloma at the edge of the stent. CONCLUSION: Interventional
      bronchoscopy should be considered feasible for management of tuberculous
      tracheobronchial stenosis. Dumon stents seem to be appropriate, since removal or
      replacement is always possible. Ultraflex stents should not be used in these
      circumstances because removal is difficult and their long-term safety is
      uncertain. EBUS could provide useful information in evaluating the condition of
      the airway wall in cases of tracheobronchial tuberculosis with potential for
      bronchoscopic intervention.

PMID- 15486403
TI  - The yield of flexible fiberoptic bronchoscopy in pediatric intensive care
      patients.
AB  - STUDY OBJECTIVE: To evaluate the contribution of flexible fiberoptic bronchoscopy
      (FFB) and BAL to the clinical management of patients in a pediatric ICU (PICU).
      SETTING AND DESIGN: A retrospective study based on medical records in a six-bed
      pediatric ICU of a tertiary care children's hospital serving as a referral center
      for airway surgery. PATIENTS AND PARTICIPANTS: One hundred consecutive infants
      and children hospitalized in a PICU, who underwent FFB with or without BAL.
      MEASUREMENTS AND RESULTS: One hundred fifty-five procedures were performed, for
      the following causes: search for airways anatomic pathologies (114 of 155
      procedures, 74%), including 55 procedures during the perioperative period of
      airway surgery; treatment of atelectasis (35 of 155 procedures, 22.5%); and BAL
      (30 of 155 procedures, 19%). Thirty-five percent of procedures had more than one
      cause. Airway pathology was observed in 79 of 114 procedures (69%). Management
      changed from conservative to surgical in 44 of 114 procedures (39%). In airway
      surgery cases, reoperation subsequent to postoperative FFB took place in 35%. BAL
      results changed antimicrobial treatment in 15 of 30 cases, with clinical
      improvement in 10 of 30 cases (33%). Treatment of atelectasis was successful in
      26 of 35 cases (74.3%). No procedure-related mortality, life-threatening
      complications, or significant changes in patient status occurred. CONCLUSIONS:
      FFB is an important and safe procedure in very sick infants and children with a
      variety of respiratory diseases, and significantly contributes to their
      management. FFB should be considered to be a PICU staff expertise.

PMID- 15486404
TI  - Top ten list in occupational pulmonary disease.

PMID- 15486405
TI  - A neutropenic patient with rapidly progressive lung lesion.

PMID- 15486406
TI  - A man with interstitial pneumonia and pancytopenia during radiotherapy.

PMID- 15486407
TI  - Usefulness of dual 67Ga and 99mTc-sestamibi single-photon-emission CT scanning in
      the diagnosis of cardiac sarcoidosis.
AB  - Cardiac sarcoidosis is potentially fatal and hence requires a precise diagnosis.
      We performed dual (67)Ga (Ga)-(99m)Tc-sestamibi (Tc) single-photon emission CT
      (SPECT) scans by superimposing a Ga-SPECT image on the myocardial outline traced
      with Tc. The usefulness of this imaging technique in the diagnosis of cardiac
      sarcoidosis was studied. The subjects in this study were 14 patients with
      sarcoidosis (mean [+/- SD] age, 52 +/- 16 years; 5 men and 9 women). An IV dose
      of Tc (74 MBq per 2 mL) was injected into patients 72 h after an IV dose of Ga
      (111 MBq per 3 mL) was injected. The dual SPECT scan was performed 30 min after
      the Tc dose was administered. The energy used for collection was 93 keV for Ga
      and 140 keV for Tc. The myocardial outline was successfully traced in all
      subjects, allowing us to check for myocardial Ga uptake and to identify its
      location. Abnormal Ga uptake in the myocardium was observed in 9 of the 14
      subjects. In seven of these nine subjects, the location of the abnormal
      myocardial Ga uptake was identical to the location of reduced Tc uptake. Abnormal
      Ga uptake disappeared in all cases following steroid therapy. Of the five
      subjects who were free of abnormal Ga uptake, two showed reduced Tc uptake, and
      these two subjects had been receiving steroid therapy. These results suggest that
      dual SPECT scanning using Ga and Tc represents a very useful diagnostic imaging
      technique since it improves the diagnostic capability of Ga-SPECT to allow the
      highly specific diagnosis of cardiac sarcoidosis.

PMID- 15486408
TI  - Sustained symptomatic, functional, and hemodynamic benefit with the selective
      endothelin-A receptor antagonist, sitaxsentan, in patients with pulmonary
      arterial hypertension: a 1-year follow-up study.
AB  - STUDY OBJECTIVES: To examine the long-term efficacy and safety of the selective
      endothelin-A receptor (ET-A) antagonist, sitaxsentan sodium, after 1 year of
      therapy in patients with pulmonary arterial hypertension (PAH). DESIGN: The study
      was a Canadian, open-label extension of at least 1-year total of active therapy
      (sitaxsentan, 100 mg/d), following a preceding, blinded, 12-week placebo
      controlled trial of sitaxsentan (placebo, or sitaxsentan, 100 mg/d or 300 mg/d),
      which had then been followed by a blinded active-therapy continuation study
      (sitaxsentan, 100 mg/d or 300 mg/d). PATIENTS: Eleven patients with PAH were
      enrolled. The condition of one patient worsened at 7 months of therapy, and the
      patient transferred to epoprostenol therapy. The remaining 10 patients
      (idiopathic [n = 3], connective tissue disease [n = 3], congenital heart disease
      [n = 4]) completed the evaluation after 1 year of active therapy. INTERVENTIONS:
      The end points of the study included the 6-min walk test, World Health
      Organization (WHO) functional class, and cardiopulmonary hemodynamic parameters.
      RESULTS: After 1 year of sitaxsentan therapy, there were significant improvements
      in 6-min walk distance (50-m treatment effect), WHO functional class, and
      hemodynamics, as compared to baseline. There were no serious adverse events, and
      no instances of hepatotoxicity or bleeding. CONCLUSION: Long-term selective ET-A
      blockade with sitaxsentan sodium is safe and may improve exercise capacity,
      functional class, and hemodynamics in patients with PAH.

PMID- 15486410
TI  - Pneumonia after tracheotomy.

PMID- 15486411
TI  - Surgical stress in ARDS open-lung biopsy.

PMID- 15486412
TI  - Monitoring the adjustment of antiasthma medications with adenosine monophosphate
      bronchoprovocation.

PMID- 15486413
TI  - Heartbeat synchronizes with respiratory rhythm only under specific circumstances.

PMID- 15486415
TI  - Caregiving and long-term mechanical ventilation.

PMID- 15486416
TI  - Don't forget the abdominal thrust.

PMID- 15486417
TI  - Radiographic opacities.

PMID- 15486418
TI  - Tracheobronchomalacia and noninvasive ventilation revisited.

PMID- 15486419
TI  - Vitamin E as a regulator of host defense against infection.

PMID- 15486420
TI  - L-type calcium channels: the low down.
AB  - L-type calcium channels couple membrane depolarization in neurons to numerous
      processes including gene expression, synaptic efficacy, and cell survival. To
      establish the contribution of L-type calcium channels to various signaling
      cascades, investigators have relied on their unique pharmacological sensitivity
      to dihydropyridines. The traditional view of dihydropyridine-sensitive L-type
      calcium channels is that they are high-voltage-activating and have slow
      activation kinetics. These properties limit the involvement of L-type calcium
      channels to neuronal functions triggered by strong and sustained depolarizations.
      This review highlights literature, both long-standing and recent, that points to
      significant functional diversity among L-type calcium channels expressed in
      neurons and other excitable cells. Past literature contains several reports of
      low-voltage-activated neuronal L-type calcium channels that parallel the unique
      properties of recently cloned CaV1.3 L-type channels. The fast kinetics and low
      activation thresholds of CaV1.3 channels stand in stark contrast to criteria
      currently used to describe L-type calcium channels. A more accurate view of
      neuronal L-type calcium channels encompasses a broad range of activation
      thresholds and recognizes their potential contribution to signaling cascades
      triggered by subthreshold depolarizations.

PMID- 15486421
TI  - Use it or lose it. Focus on: "sequential learning from multiple tutors and serial
      returning of auditory neurons in a brain area important to birdsong learning".

PMID- 15486422
TI  - Circadian modulation of temporal properties of the rod pathway in larval Xenopus.
AB  - Circadian clocks are integral components of visual systems. They help adjust an
      animal's vision to diurnal changes in ambient illumination. To understand how
      circadian clocks may adapt visual sensitivity, we investigated the spatial and
      temporal properties of optomotor responses of young Xenopus laevis tadpoles
      (Nieuwkoop and Faber, developmental stage 48) using a modified 2-alternative
      preferential-viewing method. We maintained animals in constant darkness and
      measured temporal sensitivity during their subjective day and night. We found
      that their behavioral responses can be explained in terms of 2 mechanisms with
      different temporal properties. The more sensitive mechanism operates at low
      temporal frequencies and intermediate wavelengths (lambdamax = 520 nm),
      properties consistent with rod signals. Threshold for this mechanism is
      approximately 0.04 photoisomerizations rod(-1) s(-1), consistent with single
      photon detection. A less-sensitive mechanism responds to higher temporal
      frequencies (cutoff = 12 Hz) and has broad spectral sensitivity (370-720 nm),
      consistent with multiple classes of cone signals. This cone mechanism does not
      change, but the cutoff frequency of the more sensitive rod mechanism shifts from
      0.35 Hz at night to 1.1 Hz during the subjective day, thereby enhancing the
      animal's sensitivity to dim rapidly changing stimuli. This day-night shift in rod
      temporal cutoff frequency cycles in complete darkness, characteristic of an
      endogenous circadian rhythm. The temporal properties of the behaviorally measured
      rod mechanism correspond closely with those of the electrophysiologically
      measured retinal response, indicating that the rod signals are modulated at the
      level of the outer retina.

PMID- 15486423
TI  - Effects of baclofen on spinal reflexes and persistent inward currents in
      motoneurons of chronic spinal rats with spasticity.
AB  - In the months after spinal cord injury, motoneurons develop large voltage
      dependent persistent inward currents (PICs) that cause sustained reflexes and
      associated muscle spasms. These muscle spasms are triggered by any excitatory
      postsynaptic potential (EPSP) that is long enough to activate the PICs, which
      take > 100 ms to activate. The PICs are composed of a persistent sodium current
      (Na PIC) and a persistent calcium current (Ca PIC). Considering that Ca PICs have
      been shown in other neurons to be inhibited by baclofen, we tested whether part
      of the antispastic action of baclofen was to reduce the motoneuron PICs as
      opposed to EPSPs. The whole sacrocaudal spinal cord from acute spinal rats and
      spastic chronic spinal rats (with sacral spinal transection 2 mo previously) was
      studied in vitro. Ventral root reflexes were recorded in response to dorsal root
      stimulation. Intracellular recordings were made from motoneurons, and slow
      voltage ramps were used to measure PICs. Chronic spinal rats exhibited large
      monosynaptic and long-lasting polysynaptic ventral root reflexes, and motoneurons
      had associated large EPSPs and PICs. Baclofen inhibited these reflexes at very
      low doses with a 50% inhibition (EC50) of the mono- and polysynaptic reflexes at
      0.26 +/- 0.07 and 0.25 +/- 0.09 (SD) microM, respectively. Baclofen inhibited the
      monosynaptic reflex in acute spinal rats at even lower doses (EC50 = 0.18 +/-
      0.02 microM). In chronic (and acute) spinal rats, all reflexes and EPSPs were
      eliminated with 1 microM baclofen with little change in motoneuron properties
      (PICs, input resistance, etc), suggesting that baclofen's antispastic action is
      presynaptic to the motoneuron. Unexpectedly, in chronic spinal rats higher doses
      of baclofen (20-30 microM) significantly increased the total motoneuron PIC by
      31.6 +/- 12.4%. However, the Ca PIC component (measured in TTX to block the Na
      PIC) was significantly reduced by baclofen. Thus baclofen increased the Na PIC
      and decreased the Ca PIC with a net increase in total PIC. By contrast, when a
      PIC was induced by 5-HT (10-30 microM) in motoneurons of acute spinal rats,
      baclofen (20-30 microM) significantly decreased the PIC by 38.8 +/- 25.8%,
      primarily due to a reduction in the Ca PIC (measured in TTX), which dominated the
      total PIC in these acute spinal neurons. In summary, baclofen does not exert its
      antispastic action postsynaptically at clinically achievable doses (< 1 microM),
      and at higher doses (10-30 microM), baclofen unexpectedly increases motoneuron
      excitability (Na PIC) in chronic spinal rats.

PMID- 15486424
TI  - Calcitonin gene-related peptide receptor activation produces PKA- and PKC
      dependent mechanical hyperalgesia and central sensitization.
AB  - Calcitonin gene-related peptide (CGRP), acting through CGRP receptors, produces
      behavioral signs of mechanical hyperalgesia in rats and sensitization of wide
      dynamic range (WDR) neurons in the spinal cord dorsal horn. Although involvement
      of CGRP receptors in central sensitization has been confirmed, the second
      messenger systems activated by CGRP receptor stimulation and involved in pain
      transmission are not clear. This study tested whether the hyperalgesia and
      sensitizing effects of CGRP receptor activation on WDR neurons are mediated by
      protein kinase A or C (PKA or PKC) signaling. Intrathecal injection of CGRP in
      rats produced mechanical hyperalgesia, as shown by paw withdrawal threshold
      tests. CGRP-induced hyperalgesia was attenuated significantly by the CGRP1
      receptor antagonist, CGRP8-37. The effect was also attenuated significantly by a
      PKA inhibitor (H89) or a PKC inhibitor (chelerythrine chloride).
      Electrophysiological experiments demonstrated that superfusion of the spinal cord
      with CGRP-induced sensitization of spinal dorsal horn neurons. The CGRP effect
      could be blocked by CGRP8-37. Either a PKA or PKC inhibitor (H89 or
      chelerythrine) also attenuated this effect of CGRP. These results are consistent
      with the hypothesis that CGRP produces hyperalgesia by a direct action on CGRP1
      receptors in the spinal cord dorsal horn and suggest that the effects of CGRP are
      mediated by both PKA and PKC second-messenger pathways.

PMID- 15486425
TI  - A common parieto-frontal network is recruited under both low visibility and high
      perceptual interference conditions.
AB  - A fundamental property of visual attention is to select targets from interfering
      distractors. However, attention can also facilitate the detectability of near
      threshold items presented in isolation. The extent to which these two
      perceptually challenging conditions are resolved by the same neural mechanisms is
      not well known. In the present event-related fMRI experiment, subjects performed
      a letter identification task under two perceptually challenging conditions; when
      the luminance contrast of a target letter was reduced (perceptual visibility
      manipulation) and when the target letter was flanked by distractors (perceptual
      interference manipulation). Perceptual interference recruited the right parietal
      and mid-lateral frontal cortex, while perceptual visibility activated these
      regions bilaterally. The overlap of activated areas between the two perceptual
      manipulations suggests that a single parieto-frontal network is summoned under
      both perceptual visibility and interference conditions.

PMID- 15486426
TI  - Processing of frequency-modulated sounds in the lateral auditory belt cortex of
      the rhesus monkey.
AB  - Single neurons were recorded from the lateral belt areas, anterolateral (AL),
      mediolateral (ML), and caudolateral (CL), of nonprimary auditory cortex in 4
      adult rhesus monkeys under gas anesthesia, while the neurons were stimulated with
      frequency-modulated (FM) sweeps. Responses to FM sweeps, measured as the firing
      rate of the neurons, were invariably greater than those to tone bursts. In our
      stimuli, frequency changed linearly from low to high frequencies (FM direction
      "up") or high to low frequencies ("down") at varying speeds (FM rates). Neurons
      were highly selective to the rate and direction of the FM sweep. Significant
      differences were found between the 3 lateral belt areas with regard to their FM
      rate preferences: whereas neurons in ML responded to the whole range of FM rates,
      AL neurons responded better to slower FM rates in the range of naturally
      occurring communication sounds. CL neurons generally responded best to fast FM
      rates at a speed of several hundred Hz/ms, which have the broadest frequency
      spectrum. These selectivities are consistent with a role of AL in the decoding of
      communication sounds and of CL in the localization of sounds, which works best
      with broader bandwidths. Together, the results support the hypothesis of parallel
      streams for the processing of different aspects of sounds, including auditory
      objects and auditory space.

PMID- 15486427
TI  - Role of ionotropic glutamatergic and GABAergic inputs on the firing activity of
      neurons in the external pallidum in awake monkeys.
AB  - The neurons in the external segment of the pallidum (GPe) in awake animals
      maintain a high level of firing activity. The level and pattern of the activity
      change with the development of basal ganglia disorders including parkinsonism and
      hemiballism. The GPe projects to most of the nuclei in the basal ganglia. Thus
      exploring the mechanisms controlling the firing activity is essential for
      understanding basal ganglia function in normal and pathological conditions. To
      explore the role of ionotropic glutamatergic and GABAergic inputs to the GPe,
      unit recordings combined with local injections of receptor antagonists were
      performed in awake monkeys. Observations on the effects of local application of
      the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate
      antagonist 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7
      sulfonamide, the N-methyl-D-aspartic acid (NMDA) antagonist 3-(2-carboxypiperazin
      4-yl)-propyl-1-phosphonic acid, and the GABAA antagonist gabazine as well as the
      effects of muscimol blockade of the subthalamic nucleus on the spontaneous firing
      rate, firing patterns, and cortical stimulation induced responses in the GPe
      suggested the following: sustained glutamatergic and GABAergic inputs control the
      level of the spontaneous firing of GPe neurons; both AMPA/kainate and NMDA
      receptors are activated by glutamatergic inputs; some GPe neurons receive
      glutamatergic inputs originating from areas other than the subthalamic nucleus;
      no GPe neurons became silent after a combined application of glutamate and GABA
      antagonists, suggesting that GPe neurons have intrinsic properties or
      nonionotropic glutamatergic tonic inputs that sustain a fast oscillatory firing
      or a combination of a fast and a slow oscillatory firing in GPe neurons.

PMID- 15486428
TI  - Dopamine receptor activation can reduce voltage-gated Na+ current by modulating
      both entry into and recovery from inactivation.
AB  - We tested whether dopamine receptor activation modulates the voltage-gated Na+
      current of goldfish retinal ganglion cells, using a fast voltage-clamp amplifier,
      perforated-patch whole cell mode, and a physiological extracellular Na+
      concentration. As found in other cells, activators of D1-type dopamine receptors
      and of protein kinase A reduced the amplitude of current activated by
      depolarizations from resting potential without altering the current kinetics or
      activation range. However, D1-type dopamine receptor activation also accelerated
      the rate of entry into inactivation during subthreshold depolarizations and
      slowed the rate of recovery from inactivation after single, brief
      depolarizations. Our results provide the first evidence in any preparation that
      D1-type receptor activation can produce both of these latter effects.

PMID- 15486440
TI  - Automated analysis of the auditory brainstem response using derivative estimation
      wavelets.
AB  - In this paper, we describe an algorithm that automatically detects and labels
      peaks I-VII of the normal, suprathreshold auditory brainstem response (ABR). The
      algorithm proceeds in three stages, with the option of a fourth: (1) all
      candidate peaks and troughs in the ABR waveform are identified using zero
      crossings of the first derivative, (2) peaks I-VII are identified from these
      candidate peaks based on their latency and morphology, (3) if required, peaks II
      and IV are identified as points of inflection using zero crossings of the second
      derivative and (4) interpeak troughs are identified before peak latencies and
      amplitudes are measured. The performance of the algorithm was estimated on a set
      of 240 normal ABR waveforms recorded using a stimulus intensity of 90 dBnHL. When
      compared to an expert audiologist, the algorithm correctly identified the major
      ABR peaks (I, III and V) in 96-98% of the waveforms and the minor ABR peaks (II,
      IV, VI and VII) in 45-83% of waveforms. Whilst peak II was correctly identified
      in only 83% and peak IV in 77% of waveforms, it was shown that 5% of the peak II
      identifications and 31% of the peak IV identifications came as a direct result of
      allowing these peaks to be found as points of inflection.

PMID- 15486441
TI  - Development of outward potassium currents in inner and outer hair cells from the
      embryonic mouse cochlea.
AB  - We recorded K(+) currents in inner (IHCs) and outer (OHCs) hair cells from mice
      at embryonic days 16 and 18 and on the day of birth (PO) to characterize their
      early physiological differentiation. In both cell types, outward currents
      increased in size during late embryonic development, in cells situated in both
      the apical and basal coils of the cochlea. Currents increased up to six-fold,
      with current density increasing four-fold. Currents in basal cells were generally
      larger than in the apex, and currents in IHCs were larger than in OHCs at any
      given stage. In OHCs, they were initially non-inactivating but gained the partial
      inactivation characteristic of the K(+) current of neonatal mouse cochlear hair
      cells, I(K,neo), by day 18 in the base and by P0 in the apex. In IHCs, there was
      little change, other than in amplitude, with partial inactivation already evident
      in the base by embryonic day 16. These results suggest that changes in the
      channel complement of OHCs occur within a few days of terminal mitosis, whereas
      in IHCs any such development would occur earlier. The progressive development of
      K(+) currents correlates with a developmental delay of around 2 days from the
      base to the apex of the cochlea.

PMID- 15486442
TI  - Nigerian chimpanzees (Pan troglodytes vellerosus) at Gashaka: two years of
      habituation efforts.
AB  - Cross-population comparisons of chimpanzees can shed light on the pathways of
      hominid evolution. So far, no eco-ethological data exist for the recently
      recognized subspecies Pan troglodytes vellerosus. We report on the first 2 years
      of a new long-term study from what is perhaps their last remaining stronghold:
      the Gashaka Gumti National Park, Nigeria. The mosaic habitat (woodland, lowland
      and gallery forest) receives 1,826 mm rain/year, with 4-5 months being completely
      dry. Primates at Gashaka are not hunted, and the chimpanzees are therefore
      relatively tolerant of human observers. We focused on the Gashaka-Kwano
      community, investing 3,000 h of patrols. A total of 95 sightings were achieved
      which lasted for an average of 27 min (range 1-190 min). Party size averaged 3.7
      animals (range 1-17) but was, similarly to encounter length, susceptible to a
      wide range of methodological, social and ecological factors. The Kwano community
      comprises at least 35 members which occupy a home range of at least 26 km(2),
      yielding a density of 1.3/km(2). The area represents the West African equivalent
      of a chimpanzee site similar to the forest-woodland habitat in which early humans
      might have evolved.

PMID- 15486443
TI  - A concept of value during experimental exchange in brown capuchin monkeys, Cebus
      apella.
AB  - We evaluated the response of brown capuchin monkeys to two differentially valued
      tokens in an experimental exchange situation akin to a simple barter. Monkeys
      were given a series of three tests to evaluate their ability to associate tokens
      with food, then their responses were examined in a barter situation in which
      tokens were either limited or unlimited. Capuchins did not perform barter in the
      typical sense, returning the tokens which were associated with the reward.
      However, females, but not males, showed a different response, preferring the
      higher-value token. This may indicate that they learned to prefer one token over
      the other rather than to associate the tokens with their specific rewards. This
      sex difference parallels previous findings of greater reciprocity in female brown
      capuchins than in males.

PMID- 15486444
TI  - Survey results from Ranomafana National Park: new evidence for the effects of
      habitat preference and disturbance on the distribution of Hapalemur.

PMID- 15486445
TI  - A case of pseudo-pregnancy in captive brown howler monkeys (Alouatta guariba).

PMID- 15486446
TI  - Diagnostic hysteroscopy in endometrial hyperplasia.
AB  - OBJECTIVES: To assess the reproducibility of hysteroscopic diagnosis in the
      various types of endometrial hyperplasias and to compare different
      classifications of endometrial hyperplasia from this point of view. STUDY DESIGN:
      109 endometrial hyperplasias, diagnosed in the last 5 years with hysteroscopy,
      were all biopsied and had a pathological examination. We tried to estimate the
      accuracy of hysteroscopy comparing the various classifications of endometrial
      hyperplasia to the final pathologic diagnosis. RESULTS: Using older endometrial
      hyperplasia classification, the overall diagnostic accuracy of hysteroscopy was
      76% as for the correct type of hyperplasia. Classifying them at hysteroscopy into
      two categories only, i.e. hyperplasias and neoplasias, gave a more accurate
      result (90.26%). CONCLUSIONS: The newer classification is better from the
      hysteroscopist's point of view.

PMID- 15486447
TI  - Can erythropoietin therapy improve survival?
AB  - The presence of anaemia in patients with cancer is correlated with poor clinical
      outcome, a reduced tumour response to anticancer therapy and an increased risk of
      mortality. This observation has led to speculation as to whether treatment of
      anaemia can enhance survival rates. The majority of studies have suggested that
      erythropoietic therapy either does not change or improves disease-free and/or
      overall survival. Only two studies, one in breast cancer and the other in head
      and neck cancer, both of which used epoetin outside its approved indications,
      have observed a decrease in survival in epoetin-treated patients compared with
      controls. Methodological issues and baseline imbalances between groups in
      prognostic factors for survival that may have favoured placebo treatment have
      complicated the interpretation of these studies. In contrast, a Cochrane meta
      analysis of randomised, controlled trials of epoetin in anaemic patients with
      cancer that reported survival identified 19 trials up to the end of 2001 with
      2,865 patients. This meta-analysis reported a hazard ratio for overall survival
      of 0.81 (95% CI 0.67-0.99) for adjusted data and a hazard ratio of 0.84 (95% CI
      0.69-1.02) for unadjusted data. A recent meta-analysis of nine randomised,
      controlled trials of epoetin beta (n = 1,413) suggests that use of this therapy
      is associated with a reduced risk of tumour progression. This meta-analysis also
      showed that no association existed between the risk of overall mortality or
      thromboembolic mortality and epoetin beta therapy. These results suggest that
      treatment of anaemic patients with cancer with epoetin beta is effective and
      safe.

PMID- 15486448
TI  - Optimising anaemia management with epoetin beta.
AB  - The contribution of epoetin beta to the management of cancer-related anaemia over
      the past decade has been a significant one; increased haemoglobin (Hb) levels,
      reduced transfusion need and improved patient quality of life (QoL) have been
      well documented in patients across a wide range of malignancies. In recent years,
      concerns have been raised over the inconvenience and costs associated with the
      conventional three-times weekly (tiw) epoetin dosing regimen. As a result,
      optimising therapy through less frequent dosing (i.e. once weekly) has become a
      focus of research. The NeoRecormon Once Weekly (NOW) study compared the efficacy
      and tolerability of epoetin beta 30,000 IU once weekly with a standard 10,000 IU
      tiw regimen in patients with lymphoproliferative malignancies. The study showed
      that the once weekly regimen was equally effective as the tiw regimen in
      increasing Hb levels and reducing transfusion need. Furthermore, the response to
      once weekly treatment was rapid, with 1 and 2 g/dl increases in Hb level seen at
      approximately 4 and 8 weeks, respectively. Studies with other erythropoietic
      agents have also shown the efficacy of the once weekly dosing strategy. Epoetin
      beta 30,000 IU is now approved for once weekly administration in patients with
      lymphoproliferative malignancies receiving antitumour therapy, and can be
      administered using a new 30,000 IU pre-filled syringe. Once weekly administration
      of epoetin beta offers greater convenience and should reduce administration costs
      compared with the tiw regimen.

PMID- 15486449
TI  - Evolving treatment strategies for anaemia in cancer: experience with epoetin
      beta.
AB  - Epoetin represents the standard of care in the management of cancer therapy
      related anaemia, increasing haemoglobin levels, reducing transfusion need and
      improving patient quality of life (QoL). Recent research aimed at improving
      convenience and ease of use has involved all epoetins. In particular, it has
      confirmed that epoetin beta 30,000 IU once weekly is equally effective as the
      conventional 10,000 IU three-times weekly regimen in alleviating cancer-related
      anaemia. Ongoing research aimed at improving still further the effectiveness of
      epoetins in anaemia treatment is examining the role of concomitant intravenous
      iron during epoetin beta therapy. With the recent debate over whether epoetin
      therapy has an effect on treatment outcome and survival, well-designed trials
      specifically powered to assess survival are required. The BReast cancer-Anaemia
      and the Value of Erythropoietin (BRAVE) trial is such a study, assessing the
      impact of epoetin beta on survival and QoL of patients with metastatic breast
      cancer scheduled to receive anthracycline- and/or taxane-based chemotherapy. The
      findings of such studies are expected to lead to a greater understanding of the
      optimal use of epoetins in cancer-related anaemia.

PMID- 15486450
TI  - Surgical and interventional treatment of chronic pancreatitis.
AB  - The management of patients with chronic pancreatitis (CP) remains a challenging
      problem. Main indications for surgery are intractable pain, suspicion of
      malignancy, and involvement of adjacent organs. The main goal of surgical
      treatment is improvement of patient quality of life. The surgical treatment
      approach usually involves proximal pancreatic resection, but lateral
      pancreaticojejunal drainage may be used for large-duct disease. The newer
      duodenum-preserving head resections of Beger and Frey provide good pain control
      and preservation of pancreatic function. Thoracoscopic splanchnicectomy and the
      endoscopic approach await confirmatory trials to confirm their efficiency in the
      management of CP. Common bile duct obstruction is addressed by distal Roux-en-Y
      choledochojejunostomy but when combined with dudodenal obstruction must be
      treated by pancreatic head resection. Pancreatic ascites due to disrupted
      pancreatic duct should be treated by internal drainage. The approach to CP is
      multidisciplinary, tailoring the various therapeutic options to meet each
      individual patient's needs.

PMID- 15486451
TI  - Synthesis of heparin-like oligosaccharides on polymer supports.
AB  - The biological functions of a variety of proteins are regulated by heparan
      sulfate glycosaminoglycans. In order to facilitate the elucidation of the
      molecular basis of glycosaminoglycan-protein interactions we have developed
      syntheses of heparin-like oligosaccharides on polymer supports. A completely
      stereoselective strategy previously developed by us for the synthesis of these
      oligosaccharides in solution has been extended to the solid phase using an
      acceptor-bound approach. Both a soluble polymer support and a polyethylene glycol
      grafted polystyrene resin have been used and different strategies for the
      attachment of the acceptor to the support have been explored. The attachment of
      fully protected disaccharide building blocks to a soluble support through the
      carboxylic group of the uronic acid unit by a succinic ester linkage, the use of
      trichloroacetimidates as glycosylating agents and of a functionalized Merryfield
      type resin for the capping process allowed for the construction of hexasaccharide
      and octasaccharide fragments containing the structural motif of the regular
      region of heparin. This strategy may facilitate the synthesis of
      glycosaminoglycan oligosaccharides by using the required building blocks in the
      glycosylation sequence.

PMID- 15486453
TI  - Asymmetric synthesis and affinity of potent sialyltransferase inhibitors based on
      transition-state analogues.
AB  - Inhibitors that are structurally related to the transition-state model of the
      proposed SN1-type mechanism of sialyl transfer, exhibit particularly high binding
      affinities to alpha(2-6)sialyltransferases. Furthermore, replacing the neuraminyl
      residue with a simple aryl or hetaryl ring and substituting the carboxylate group
      for a phosphonate moiety, improves both binding affinity and synthetic
      accessibility. Herein we report on the synthesis and inhibition of a wide range
      of novel, potent transition-state analogue based alpha(2-6)sialyltransferase
      inhibitors comprising a planar anomeric carbon, an increased distance between the
      anomeric carbon and the CMP leaving group, and at least two negative charges. We
      also present a short, efficient asymmetric synthesis of the most promising benzyl
      inhibitors, providing rapid access to large quantities of highly potent,
      stereochemically-pure (>96% de) inhibitors for further biological investigation
      (e.g.(R)-3b, Ki = 70 nM).

PMID- 15486452
TI  - Synthesis and conformational characterization of the epidermal growth factor-like
      domain of blood coagulation factor IX carrying xylosyl-glucose.
AB  - Solid-phase synthesis of glycopeptide generally requires the protection of both
      peptide side chains and hydroxyl groups of the carbohydrate portion. However, if
      the mild coupling conditions are used, the protection of the carbohydrate portion
      can be omitted. In this paper, we demonstrated it by the synthesis of Fmoc-serine
      carrying unmasked xylosyl glucose followed by the solid-phase synthesis of
      epidermal growth factor (EGF)-like domain of factor IX (45-87) using the unit.
      The product was well characterized by enzymatic digestion, amino acid analysis
      and mass spectrometry. The secondary structure of the product as well as
      glucosylated and non-glycosylated EGF-like domain was characterized by circular
      dichroism (CD) spectroscopy.

PMID- 15486454
TI  - Asymmetric synthesis and reactivity of potent sialyltransferase inhibitors based
      on transition-state analogues: supplementary data.

PMID- 15486455
TI  - Ligands of the asialoglycoprotein receptor for targeted gene delivery, part 1:
      Synthesis of and binding studies with biotinylated cluster glycosides containing
      N-acetylgalactosamine.
AB  - In order to develop the non-viral Bioplex vector system for targeted delivery of
      genes to hepatocytes, we have evaluated the structure-function relationship for a
      number of synthetic ligands designed for specific interaction with the hepatic
      lectin ASGPr. Biotinylated ligand derivatives containing two, three or six beta
      linked N-acetylgalactosamine (GalNAc) residues were synthesized, bound to
      fluorescent-labeled streptavidin and tested for binding and uptake to HepG2 cells
      using flow cytometry analysis (FACS). Uptake efficiency increased with number of
      displayed GalNAc units per ligand, in a receptor dependent manner. Thus, a
      derivative displaying six GalNAc units showed the highest uptake efficacy both in
      terms of number of internalizing cells and increased amount of material taken up
      per each cell. However, this higher efficiency was shown to be due not so much to
      higher number of sugar units, but to higher accessibility of the sugar units for
      interaction with the receptor (longer spacer). Improving the flexibility and
      accessibility of a trimeric GalNAc ligand through use of a longer spacer markedly
      influenced the uptake efficiency, while increasing the number of GalNAc units per
      ligand above three only provided a minor contribution to the overall affinity. We
      hereby report the details of the chemical synthesis of the ligands and the
      structure-function studies in vitro.

PMID- 15486456
TI  - Chemoenzymatic synthesis of diverse asparagine-linked alpha-(2,3)
      sialyloligosaccharides.
AB  - Partial sialyl transfer reaction by alpha-(2,3)-sialyltransferase toward (Gal
      beta-1,4-GlcNAc-beta-1,2-Man-alpha-1,6/1,3-)(2)Man-beta-1,4-GlcNAc-beta-1,4
      GlcNAc-beta-1-asparagine-Fmoc 1 was examined to obtain mono-alpha-(2,3)
      sialyloligosaccharides and then branch-specific exo-glycosidase digestion (beta-D
      galactosidase, N -acetyl-beta-D-glucosaminidase and alpha-D-mannosidase) toward
      the asialo-branch was performed to obtain diverse asparagine-linked complex type
      alpha-(2,3)-sialyloligosaccharides. In addition, two kinds of
      disialyloligosaccharides in which the sialyl linkage was a mixture of alpha-(2,3)
      and alpha-(2,6)-types were also specifically prepared by an additional alpha
      (2,6)-sialyltransferase reaction toward mono-alpha-(2,3)-sialyloligosaccharides
      thus obtained.

PMID- 15486457
TI  - Synthesis of the Lewis b hexasaccharide and HSA-conjugates thereof.
AB  - An efficient and short route has been elaborated for the aminopropyl spacer
      equipped Leb hexasaccharide. For the preparation of HSA-conjugates of this
      oligosaccharide, the use of disuccinimidyl suberate (DSS) and disuccinimidyl
      glutarate (DSG) as cross-linker reagents has been evaluated. This conjugation
      method emerged as being faster and easier to monitor by standard MALDI-TOF
      spectrometry than squarate ester based conjugations of similar efficiency if DSS
      is used as cross-linker.

PMID- 15486458
TI  - Synthesis of fluorine substituted oligosaccharide analogues of monoglucosylated
      glycan chain, a proposed ligand of lectin-chaperone calreticulin and calnexin.
AB  - As a part of a exploring the N-glycan-mediated glycoprotein quality control in
      endoplasmic reticulum, 2-fluorinated derivative Glcalpha1 --> 3Man(F) 1,
      Glcalpha1 --> 3Man(F)alpha1 --> 2Man2, and Glcalpha1 --> 3Man(F)alpha1 -->
      2Manalpha1 --> 2Man 3 were synthesized in a concise manner. These
      oligosaccharides were subjected to binding studies with calreticulin by using
      isothermal titration calorimetry. It was revealed that disaccharide 1 was a poor
      ligand, while tri- (2) and tetrasaccharide (3) had observable affinity.

PMID- 15486459
TI  - Cloning and tissue distribution of the human B3GALT7 gene, a member of the
      beta1,3-Glycosyltransferase family.
AB  - We report here the cloning and tissue distribution of the human B3GALT7 gene, a
      member of the beta1,3-Glycosyltransferase family, structurally related to the
      beta1,3-Galactosyltransferase family and beta1,3- N 
      acetylglucosaminyltransferase family, isolated from a human lung cDNA library.
      B3GALT7 is mapped to chromosome 19q13.2 by browsing the UCSC genomic database. It
      contains an ORF with length of 1191bp, encoding a protein with a signal peptide
      sequence and galactosyl-T domain, and its molecular weight and isoelectric point
      is predicted to be 43.3 kDa and 8.67 respectively. The molecular weight of the
      protein when expressed in E. coli corresponded to that expected. Northern
      blotting showed that B3GALT7 was highly expressed in lung, throat and ileum,
      whereas the expression level was low in tongue, breast, uteri, testis. In
      addition, it was also demonstrated that B3GALT7 is differentially transcribed in
      human tumor cell lines.

PMID- 15486460
TI  - Unaltered complex N-glycan profiles in Nicotiana benthamiana despite drastic
      reduction of beta1,2- N -acetylglucosaminyltransferase I activity.
AB  - UDP-GlcNAc:alpha3-D-mannoside beta1,2- N -acetylglucosaminyltransferase I (GnTI;
      EC 2.4.1.101) is a Golgi-resident glycosyltransferase that is essential for the
      processing of oligomannose to hybrid and complex N-glycans in higher eukaryotes.
      The cDNA of Nicotiana tabacum GnTI has been cloned and characterised previously.
      To assess the influence of GnTI expression levels on the formation of complex N
      glycans we used posttranscriptional gene silencing to knock down the expression
      of GnTI in the tobacco related species Nicotiana benthamiana. 143 independent
      transgenic plants containing GnTI constructs in either sense or antisense
      orientation were generated. 23 lines were selected for measurement of GnTI
      activity and 10 lines thereof showed a reduction of more than 85% in in vitro
      assays as compared to wildtype plants. GnTI reduction was stably inherited and
      did not interfere with the viability of the transformants. Noteworthy one line,
      34S/2, exhibited a residual GnTI activity below the detection limit. beta1,2- N 
      acetylglucosaminyltransferase II (GnTII), an enzyme which acts further downstream
      in the N-glycosylation pathway, as well as other control enzymes (alpha
      mannosidase, beta- N -acetylglucosaminidase) were not affected indicating the
      specific downregulation of GnTI. Remarkably, immunoblots and mass spectrometric N
      glycan profiling revealed no significant changes of the total N-glycan comparable
      to wildtype plants.

PMID- 15486461
TI  - Hepatic regulation of apolipoprotein B.

PMID- 15486462
TI  - The physiological role of triacylglycerol hydrolase in lipid metabolism.

PMID- 15486463
TI  - Insight into the role of LCAT from mouse models.

PMID- 15486464
TI  - The Farnesoid X Receptor (FXR) as modulator of bile acid metabolism.

PMID- 15486465
TI  - SR-BI and protein-protein interactions in hepatic high density lipoprotein
      metabolism.

PMID- 15486466
TI  - Apolipoprotein E-induced cell signaling in the vessel wall.

PMID- 15486467
TI  - Common variation in genes involved in HDL metabolism influences coronary heart
      disease risk at the population level.

PMID- 15486469
TI  - Lipids and the elderly.

PMID- 15486468
TI  - Anti-inflammatory properties of HDL.

PMID- 15486470
TI  - The BOLD response: a new look at an old riddle.
AB  - Functional imaging has struggled for two decades to establish a quantitative link
      between the neuronal activity and the change in signal obtained. This review
      proposes a division of neuronal activity into a component relating to the
      electrical discharge activity and a component relating to the size of the
      activated neuronal population. These two components are argued to have opposing
      influences on the BOLD signal. The influence of these two components on the BOLD
      signal, are summarised in the standard model.

PMID- 15486471
TI  - Development of the inner ear in Splotch mutant mice.
AB  - The Splotch mouse, a Pax 3 mutation, represents a model of Waardenburg syndrome
      I. We show that the homozygous Splotch mutation (Sp(2H)) is associated with
      severe defects that prevent the formation of the cochlea and vestibulo-cochlear
      ganglion. To clarify the role of Pax 3 in inner ear formation, we examined the
      expression of polysialic acid (PSA) associated with neural cell adhesion molecule
      (NCAM). In accordance with the occurrence of phenotypic abnormalities, PSA NCAM
      was expressed early in otocyst development in the otic epithelium and the
      vestibulo-cochlear anlage. During the period of vestibular and cochlear ganglia
      formation, PSA NCAM expression was decreased. In the late phase of embryonic
      development, the expression of calcium binding proteins (S100) in the vestibulo
      cochlear ganglion was also decreased. Minor differences in S100 immunostaining
      were found postnatally between the cochleas of heterozygous and wild type
      animals.

PMID- 15486473
TI  - Neural correlates of the 'Aha! reaction'.
AB  - An 'Aha! reaction' is a brief moment of exceptional thinking where an unexpected
      change in one's mental perspective reveals the solution to an otherwise
      intractable problem. In this event-related fMRI study, subjects read
      incomprehensible sentences followed by solution cues that were used to evoke such
      a reaction by triggering an alternative interpretation of the critical concepts.
      For 73% of the trials, subjects attributed their failure in the initial stage of
      sentence presentation to "having thought about it in another direction". This
      behavior implies that the breaking of mental impasse is a critical component of
      the Aha! reaction phenomenon. During the Aha! reaction we observed anterior
      cingulate and left lateral prefrontal cortical activation, which are two areas
      known to mediate cognitive conflict.

PMID- 15486472
TI  - Nitric oxide inhibits complex I following AMPA receptor activation via
      peroxynitrite.
AB  - We investigated the role of nitric oxide (NO) on mitochondrial complexes
      activity, following short-term non-desensitizing activation of AMPA receptors
      with kainate (KA) plus cyclothiazide (CTZ), in cultured rat hippocampal neurons.
      In these conditions, we observed a decrease in the activity of mitochondrial
      complexes I, II/III, and IV. A selective neuronal nitric oxide synthase
      inhibitor, 7-Nitroindazole, prevented the decrease in the activity of
      mitochondrial complex I, but not for the other complexes. Exposure to KA plus CTZ
      also increased cyclic GMP levels significantly, and led to increased levels of 3
      nitrotyrosine, a biomarker for peroxynitrite production. Taken together, our
      results suggest that non-desensitizing activation of AMPA receptors causes
      inhibition of mitochondrial complex I via peroxynitrite.

PMID- 15486474
TI  - Your hand movements in my somatosensory cortex: a visuo-kinesthetic function in
      human area 2.
AB  - Does viewing someone's actions activate a viewer's somatosensory cortex? We
      tested if visual information of limb movements activated limb sections in
      somatosensory areas that are normally engaged in kinesthetic processing of the
      limb. We showed, with functional magnetic resonance imaging in 17 right-handed
      healthy subjects, that passive observation of flexion-extension movements of an
      experimenter's right hand activated the observer's contralateral hand section of
      area 2 which is involved in kinesthetic processing of right hand movements. This
      could be interpreted as a pragmatic function of the brain that permits visual
      information to reach the somatosensory area, and suggests human area 2 has an
      association function between kinesthesia and vision.

PMID- 15486475
TI  - Potential roles for presenilin-1 in oxygen sensing and in glial-specific gene
      expression.
AB  - The integral membrane glycoprotein presenilin-1 (PS1), in concert with beta
      secretase and beta amyloid precursor protein (betaAPP), orchestrate cleavage of
      betaAPP into amyloidogenic Abeta peptides. To gain further insight into PS1
      function, we undertook a gene expression profiling study that interrogated the
      expression of 12,000 genes in the forebrain of PS1-hypomorphic mice that exhibit
      highly attenuated PS1 activity. Using stringent RNA screening, DNA array and
      Northern assay, we report significant down-regulation in the expression of
      betaAPP and hypoxia inducible factor-1 alpha (HIF-1alpha), and a marked up
      regulation in the expression of glial-specific markers that include S100beta
      protein, glycerol phosphate dehydrogenase, and glial fibrillary acidic protein.
      These data suggest potential roles for PS1 in the cellular response to hypoxia
      and glial-specific gene expression.

PMID- 15486476
TI  - Expression of Fc epsilon receptor I on primary sensory neurons in mice.
AB  - We investigated whether IgE receptors are expressed on sensory neurons in mice.
      Immunostaining revealed that the high affinity IgE receptor FcepsilonRI was
      expressed in cultured dorsal root ganglion cells and that FcepsilonRI
      immunoreactive cells were mainly positive for the pan-neuronal marker protein
      gene product 9.5. Many FcepsilonRI-immunoreactive neurons were small or medium in
      size. IgE was bound to cultured neurons but not glial cells from the ganglia.
      FcepsilonRI-immunoreactive cells were also positive for the high affinity IgG
      receptor FcgammaRI. The expression level of FcepsilonRI was lower than that of
      FcgammaRI. FcepsilonRI-like immunoreactivity was localized on nerve fibers in the
      skin. The results suggest that IgE acts directly on primary sensory neurons as
      well as mast cells.

PMID- 15486477
TI  - Passive music listening spontaneously engages limbic and paralimbic systems.
AB  - In this PET study, non-musicians passively listened to unfamiliar instrumental
      music revealed afterward to elicit strongly pleasant feelings. Activations were
      observed in the subcallosal cingulate gyrus, prefrontal anterior cingulate,
      retrosplenial cortex, hippocampus, anterior insula, and nucleus accumbens. This
      is the first observation of spontaneous responses in such limbic and paralimbic
      areas during passive listening to unfamiliar although liked music. Activations
      were also seen in primary auditory, secondary auditory, and temporal polar areas
      known to respond to music. Our findings complement neuroimaging studies of
      aesthetic responses to music that have used stimuli selected by subjects or
      designed by experimenters. The observed pattern of activity is discussed in terms
      of a model synthesizing emotional and cognitive responses to music.

PMID- 15486478
TI  - Imaging of gene expression during long-term potentiation.
AB  - Long term potentiation (LTP) at hippocampal Schaffer collateral-CA1 synapses
      involves an early and a late phase, where only the latter is sensitive to protein
      synthesis inhibitors. Here we characterized the dynamics of protein synthesis
      associated with the induction of L-LTP using a transgenic mouse model in which a
      cAMP responsive element (CRE)-regulated promoter drives production of an enhanced
      yellow fluorescent protein (eYFP). We found that eYFP fluorescence increased
      after less than 30 min following L-LTP induction. Application of transcription
      and translation suppressors and the NMDA receptor antagonist D-AP5 inhibited the
      L-LTP and prevented the rise in eYFP levels. The early-phase of LTP was not
      affected by inhibiting protein synthesis.

PMID- 15486479
TI  - BDNF down-regulates the caspase 3 pathway in injured geniculo-cortical neurones.
AB  - Visual cortex ablation in newborn rats causes a rapid and almost complete
      degeneration of neurones in the dorsal lateral geniculate nucleus (dLGN), as a
      consequence of the axotomy of geniculo-cortical fibres. Death of dLGN neurones
      occurs by apoptosis and is partially prevented (approximately 50%) by intraocular
      delivery of brain-derived neurotrophic factor (BDNF). Here we investigated the
      molecular mechanisms of BDNF-mediated neuroprotection. We found that exogenous
      administration of BDNF partially decreases (approximately 50%) the up-regulation
      of apoptotic proteins (phosphorylated c-Jun, cytochrome C and cleaved caspase 3),
      that occurs in dLGN neurones following visual cortex ablation at postnatal day 7.
      These results demonstrate that the neuroprotective action of BDNF on axotomised
      dLGN neurones involves the partial blockade of well-characterised apoptotic
      pathways.

PMID- 15486480
TI  - Within- and between-channel gap detection in the human auditory cortex.
AB  - We examined the neural correlates associated with a short gap between two
      identical pure tones (within-channel) and between two different tones (between
      channel) in an odd-ball paradigm. Gap durations were selected such that a gap
      between identical tones was as discriminable as a gap between two different
      tones. Spatio-temporal dipole source modeling of electrophysiological data
      revealed a significant difference between standard and deviant gap stimuli, with
      mismatch negativity responses that were comparable in amplitude and latency for
      within- and between-channel conditions. Therefore, the ability to automatically
      register discontinuity (i.e., gap) within and between channels is comparable
      despite significant differences in gap size. The dipole source modeling suggests
      that both within- and between-gap signals are represented in or near the primary
      auditory cortex.

PMID- 15486481
TI  - Brain stem evoked response to forward and reversed speech in humans.
AB  - Speech stimuli played in reverse are perceived as unfamiliar and alien-sounding,
      even though phoneme duration and fundamental voicing frequency are preserved.
      Although language perception ultimately resides in the neocortex, the brain stem
      plays a vital role in processing auditory information, including speech. The
      present study measured brain stem frequency-following responses (FFR) evoked by
      forward and reverse speech stimuli recorded from electrodes oriented horizontally
      and vertically to measure signals with putative origins in auditory nerve and
      rostral brain stem, respectively. The vertical FFR showed increased amplitude due
      to forward speech. It is concluded that familiar phonological and prosodic
      properties of forward speech selectively activate central brain stem neurons.

PMID- 15486482
TI  - Distributed representation of sound intensity in the rat auditory cortex.
AB  - We epipially mapped tone-burst-evoked potentials over the rat auditory cortex,
      and investigated the representation of intensity information. The experiments
      were designed to elucidate how the auditory cortex represents a steady-state
      plateau sound pressure level (SPL) and dynamic onset temporal structure, i.e.,
      the rate of pressure change (in Pa/s), and how the representations differ across
      the auditory fields. The anterior and ventral fields have spatial axes of the
      rate of pressure change. Characteristic frequency (CF) locations mainly handle
      the dynamic state, while off-CF locations have the potential to code the steady
      state. Each field represents the intensity information differently, particularly
      at the off-CF locations. These results suggest that intensity information is
      distributed in various aspects in the multiple auditory fields.

PMID- 15486483
TI  - ERP evidence of MI activation without motor response execution.
AB  - There has been controversy concerning the activity of the primary motor cortex
      (MI) during the mental rehearsal of movement (motor imagination). In this study
      we found that the lateralized readiness potential (LRP), an event-related
      potential probably generated in MI, appeared with similar latencies during both
      trials requiring execution of hand movements and trials requiring only their
      mental rehearsal, regardless of whether misleading pre-cues that increased
      latency were employed. However, LRPs obtained during imagination trials had
      smaller amplitudes. We conclude that MI is involved in motor imagination as well
      as in preparing overt movement, and that in overt movement the LRP sums neural
      activity common to these two situations and neural activity exclusive to overt
      movement.

PMID- 15486484
TI  - Stimulation of PAR-2 excites and sensitizes rat cutaneous C-nociceptors to heat.
AB  - Proteinase-activated receptor 2 (PAR-2) is expressed on many nociceptive neurons.
      Application of PAR-2 agonists has been shown to induce behavioral signs of
      hyperalgesia. We investigated effects of the rat PAR-2 agonist SLIGRL-NH2 in the
      isolated rat skin-saphenous nerve preparation. SLIGRL-NH2 (100 microM) excited
      20% of all C-fiber nociceptors tested. In addition, C-fiber nociceptors were
      sensitized to heat after SLIGRL-NH2 application resulting in an increase in
      response magnitude and a decrease of heat threshold. The PAR-2-inactive control
      peptide LRGILS-NH2 had no effect. The mechanical sensitivity of C-fibers was not
      affected by SLIGRL-NH2. PAR-2-mediated excitation and sensitization of primary
      nociceptors may contribute to PAR-2-mediated hyperalgesia.

PMID- 15486485
TI  - A neural model of quantity discrimination.
AB  - A neural network model is proposed with the ability to extract abstract numerical
      representation from visual input. It simulates properties of a number detection
      system which is hypothesized to underlie simple language-independent numerical
      abilities. The network has three layers where the first layer computes the sum of
      the nearest neighbour inputs. The first layer is also augmented with
      multiplicative gating and gradient tonic activation which prevents interference.
      The second layer implements local lateral inhibition which enables a single node
      to represent a single object. The third layer exhibits number-tuning similar to
      recently described responses of neurons in the prefrontal cortex. Computer
      simulations showed that network response does not depend on visual attributes
      like the object's size, position or shape. The model is based on several
      biophysical mechanisms such as multiplicative interaction on dendrites,
      independent processing on different dendritic branches and disinhibition by
      glutamate spill-over on kainate receptors on inhibitory axons.

PMID- 15486486
TI  - Identification of a 35 kDa protein in rat spinal ganglia and sensory fibers.
AB  - A 35 kDa protein was purified from rat spinal ganglia and sensory fibers.
      Combined direct trypsin digest and liquid chromatography ion trap mass
      spectrometry analysis, the 35 kDa protein was identified as annexin V. We then
      studied the distribution of serum antibodies to annexin V in patients with
      peripheral neuropathy. We found serum positive antibodies to annexin V only in
      some patients with immune-mediated neuropathy. This indicated that humoral immune
      responses to annexin V might play a role in the pathogenesis of autoimmune
      sensory neuropathy or sensory neuronopathy.

PMID- 15486487
TI  - Speech-sound discrimination in neonates as measured with MEG.
AB  - Magnetic brain responses to speech sounds were measured in 10 healthy neonates.
      The stimulation consisted of a frequent vowel sound [a:] with a steady pitch
      contour, which was occasionally replaced by the vowel [i:] with a steady pitch,
      or the vowel [a:] with a rising pitch, manifesting a change of intonation. The
      magnetic mismatch-negativity response (MMNm) was obtained and successfully
      modelled to the speech sound quality change in all infants and to the intonation
      change in 6 infants. The present results indicate that auditory-cortex speech
      sound discrimination may well be studied with magnetic recordings as early as in
      newborn infants.

PMID- 15486488
TI  - Inhibition of amyloid-beta-induced neurotoxicity and apoptosis by moderate
      ethanol preconditioning.
AB  - Consumers of moderate amounts of ethanol have a lower risk of Alzheimer's
      dementia than do abstainers. In Alzheimer's disease the brain contains many
      extracellular plaques composed of amyloid-beta (Abeta), a neurotoxic protein
      linked to pathogenesis of the disease. Here we report that moderate ethanol
      preconditioning (20-30 mM for 6 days) of organotypic hippocampal-entorhinal slice
      cultures prevents Abeta-induced neurotoxicity and apoptosis as measured by media
      lactate dehydrogenase levels and staining with propidium iodide and Hoechst
      33342. With Abeta, as with our previous studies of the neurotoxic HIV-1 protein
      gp120, moderate ethanol preconditioning may interfere with various glial-mediated
      neurotoxic responses in the slices to Abeta. In addition, we found that moderate
      ethanol preconditioning causes an almost 3-fold increase in brain levels of heat
      shock protein 70 (hsp70), a protective molecular chaperone. Our results suggest
      possible molecular mechanisms underlying the protective effect of moderate
      drinking against Alzheimer's dementia.

PMID- 15486489
TI  - MAO-A gene polymorphisms are associated with major depression and sleep
      disturbance in males.
AB  - We investigated whether the genetic variants of the MAO-A gene were associated
      with major depression and/or the clusters of depressive symptoms. The EcoRV and
      the uVNTR polymorphisms were studied in a population of 191 patients with major
      depression and 233 control subjects. The EcoRV polymorphism was found to be
      associated with depression in males but not in females. Haplotype analysis
      revealed that one of the haplotypes (EcoRV2-uVNTR1) was significantly more
      frequent among male patients than male controls. Among the HAMD symptom clusters,
      insomnia scores were significantly higher in male patients carrying allele 2 of
      the EcoRV polymorphism. These data suggest that the EcoRV and uVNTR polymorphisms
      may be involved in the pathogenesis of major depression and associated with
      insomnia in depressed patients.

PMID- 15486490
TI  - Effects of MPSS and a potent iNOS inhibitor on traumatic spinal cord injury.
AB  - ONO-1714, a selective inhibitor of inducible nitric oxide synthetase (iNOS)
      attenuated the increase of apoptosis and improved the functional outcome of
      urinary bladder after traumatic spinal cord injury. These findings suggest that
      iNOS plays a role in the process of SCI. Early treatment with 30 mg/kg
      methylprednisolone sodium succinate (MPSS) could also inhibit the expression of
      iNOS gene, apoptosis and the loss of urinary bladder function. We confirmed that
      early MPSS treatment may prevent injury associated with apoptosis and urinary
      bladder disability by reducing iNOS mRNA. However, delayed single MPSS treatment
      8 h after spinal cord injury was not effective. Early repeated MPSS treatment
      might allow greater recovery from acute spinal cord injury.

PMID- 15486491
TI  - Quetiapine regulates FGF-2 and BDNF expression in the hippocampus of animals
      treated with MK-801.
AB  - Fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic factor (BDNF)
      are trophic factors, widely distributed in the adult brain, whose expression can
      be modulated by psychoactive drugs. Administration of the atypical antipsychotic
      quetiapine resulted in a marked elevation of FGF-2 and BDNF mRNA levels in the
      rat hippocampus, but only under conditions of reduced NMDA receptor activity.
      These effects were drug-specific, given that they were not observed with the
      conventional antipsychotic haloperidol; and anatomically defined, since no
      similar effect was observed in striatum, prefrontal or frontal cortex. These
      results suggest that quetiapine may promote neuroplasticity via the up-regulation
      of neurotrophic factors when NMDA-mediated transmission is perturbed.

PMID- 15486492
TI  - High activity of K+-dependent plasmalemmal Na+/Ca2+ exchangers in hippocampal CA1
      neurons.
AB  - Ca(2+) influx via reversed K(+)-dependent (NCKX) and/or K(+)-independent (NCX)
      plasmalemmal Na(+)/Ca(2+) exchangers may play a role in neuronal death following
      global brain ischemia to which CA1 neurons are particularly vulnerable.
      Therefore, this work tested whether the rates of Ca(2+) influx via reversed NCKX
      or NCX in cultured rat CA1 neurons differ from those in forebrain neurons (FNs)
      or cerebellar granule cells (CGCs). The NCKX-mediated Ca(2+) influx was several
      times more rapid in CA1 neurons than in FNs or CGCs and was not affected by
      Na(+)/Ca(2+) exchange inhibitors, KB-R7943 or bepridil. NCKX reversal inhibitors
      are not yet available. Their development would greatly facilitate further testing
      the role of NCKX in ischemic death of CA1 neurons.

PMID- 15486493
TI  - Induction of VEGF and its Flt-1 receptor after sciatic nerve crush injury.
AB  - Expression of vascular endothelial growth factor and its receptors Flt-1 and Flk
      1 was studied in lumbar spinal cord after sciatic nerve crush injury.
      Immunohistochemical staining revealed strikingly different distribution of VEGF,
      Flt-1, and Flk-1 in lumbar motor neurons. VEGF was observed both in the nuclei
      and perikarya, while Flk-1 had cytoplasmic and Flt-1 perinuclear localization.
      Real-time RT-PCR showed a significant increase in the expression of VEGF and Flt
      1 on the injured side of the lumbar spinal cord. The increased level of VEGF was
      also detected by immunoblot. Here we show that lumbar motor neurons increase the
      expression of VEGF and Flt-1 in response to injury. We propose that VEGF/Flt-1
      signaling may be involved in regeneration of the spinal motor neurons.

PMID- 15486494
TI  - Selective activation of the nucleus accumbens during risk-taking decision making.
AB  - This study implemented a risk-taking task during fMRI to probe the brain
      circuitry involved in risk-taking decision-making in 12 healthy control subjects.
      Partially supporting the initial hypotheses, deliberation prior to selection of
      safe relative to risky responses generated greater activation in the inferior
      frontal cortex, superior temporal gyrus, and middle temporal gyrus; and
      deliberation prior to selection of risky relative to safe responses generated
      greater activation in medial frontal cortex, occipital cortex, nucleus accumbens
      and caudate. Additionally, accumbens activation correlated positively with the
      harm avoidance subscale of the Temperament and Character Inventory (TCI) 125.
      These findings may provide target neural systems to study in subjects who exhibit
      problematic risk-taking behaviors and may partially explain why certain risky
      behaviors occur.

PMID- 15486495
TI  - Neural dynamics in human imitation revealed by ERP surface topography.
AB  - To clarify the neural dynamics in human motor imitation, we examined event
      related potentials (ERP) for a reaction time task that required responses to an
      actor's finger motions with identical motions. Compared with a control task
      (reaction to an LED illumination), the ERP surface topography in the imitative
      reaction was differentiated at around 120-200 ms post-cueing, showing an early
      sensitivity to the response hand over the pre-central region. This result
      suggested that activities around the motor areas were facilitated in the
      imitative reaction, which is consistent with recent neuroimaging studies.
      However, taken together with that there were no differences in reaction times,
      the early ERP latency of conditional divergence indicated that neural activities
      related to imitation are visual responses and do not directly lead to motor
      acceleration.

PMID- 15486496
TI  - Adenosine A1 receptor-dependent G-protein activity in the rat brain during
      prolonged wakefulness.
AB  - Adenosine accumulates in the basal forebrain during prolonged wakefulness and
      induces sleep. There is abundant evidence showing that the sleep-inducing effects
      are mediated locally in the basal forebrain through the adenosine A1 receptor. In
      previous studies an increase in the mRNA expression but no apparent change in the
      ligand binding of the A1 receptors have been found. In the present study we used
      [(35)S]GTPgammaS autoradiography to assess regional A1 receptor dependent G
      protein activity in rat brain during prolonged wakefulness and recovery sleep. We
      found that the G-protein activity was increased in the cortex but not in the
      basal forebrain during the first hours of sleep deprivation, suggesting different
      A1 receptor mediated responses to increasing adenosine concentrations in
      different brain areas.

PMID- 15486497
TI  - Rimonabant, a CB1 antagonist, blocks nicotine-conditioned place preferences.
AB  - The effects of Rimonabant (SR141716), an antagonist at cannabinoid CB1 receptors,
      were evaluated in animal models for subjective and rewarding effects of nicotine.
      Acute administration of 1 or 3 mg/kg SR141716 blocked expression of nicotine
      induced conditioned place preferences. SR141716 (0.3-3 mg/kg) was also studied in
      rats trained to discriminate nicotine from saline under a fixed-ratio schedule of
      food delivery. In contrast to nicotine replacement therapy and bupropion,
      SR141716 did not have nicotine-like discriminative effects and did not alter the
      dose-response curve for nicotine discrimination. These findings support the
      proposed use of SR141716 for smoking cessation and indicate that it would
      selectively reduce the influence of environmental stimuli that contribute to
      persistent smoking behavior, without affecting subjective responses to nicotine.

PMID- 15486498
TI  - Cortisol levels and time-discounting of monetary gain in humans.
AB  - This study was conducted to examine the relationship between cortisol levels and
      preference to a small immediate over a larger delayed monetary reward. The degree
      of preference to a small immediate reward (a time-discounting rate) was
      investigated with an economic decision-making task in which each subject made an
      inter-temporal choice between (a) 10,000 yen available immediately and (b) an
      equal or larger amount of money after a delay of one year. The time-discounting
      rate was defined as [the required minimal amount of the delayed monetary gain for
      (b) to be preferred]-10,000/10, 000. Low cortisol levels were shown to associate
      with a large time-discounting rate, indicating that subjects with low cortisol
      levels may be impulsive in inter-temporal choice.

PMID- 15486499
TI  - Using technology to trace our steps for the future...

PMID- 15486501
TI  - New home telehealth toolkit available.
AB  - A new Home Telehealth Toolkit is available for those interested in establishing a
      new home telehealth program or improving an existing one. Developed by members of
      the American Telemedicine Association's (ATA) Home Telehealth Special Interest
      Group (SIG) contains guidelines, procedures, and sample protocols that can be
      adapted for all phases of a home care telehealth program.

PMID- 15486502
TI  - The impact of technology on the "older" nurse: findings of the study: part 2.
AB  - This article presents the results of a study identifying older nurses' response
      to using various technology in their practice. This study measured nurses working
      with wireless peripheral devices, such as blood pressure cuffs, pulse oximeters,
      scales, glucometers, and digital thermometers, and monitoring units that were
      placed in the patient's home. Findings have implications for both older and
      younger clinicians as these types of products and systems can affect
      productivity, visit time, and assessment accuracy.

PMID- 15486503
TI  - Matching telehealth applications to the patient, clinician, and agency's needs.
AB  - Telehealth offers many opportunities to provide evidence-based, cost-effective
      home care practice. To ensure success administrators, managers, and clinicians
      must identify their agency's telehealth goals and compare these with technology
      manufacturers' recommendations. This article provides a list of considerations
      agencies can use to evaluate telehealth programs objectively. Successful
      telehealth applications are also presented.

PMID- 15486504
TI  - CMS details coverage of electrical stimulation and electromagnetic therapy for
      wound treatment in home health setting.

PMID- 15486505
TI  - What you need to know about home blood pressure telemonitoring: but may not know
      to ask.
AB  - Home blood pressure (BP) telemonitoring allows patients to take their BP, store
      the data, and then transmit data by phone to a healthcare provider. Research to
      date shows that home BP telemonitoring is accurate and helps patients gain
      control over their blood pressure. When used regularly, home BP telemonitoring
      can improve control and help reduce health problems associated with hypertension.

PMID- 15486506
TI  - Orienting the clinician to point of service systems.
AB  - Today's home care clinicians are expected to begin employment with basic computer
      skills and to learn informatics skills applicable to the position. This article
      discusses the technology competencies clinical home care staff must master in
      agencies that use Point of Service (POS) documentation systems. It also shares
      tips that facilitate new clinicians' orientations to a POS system.

PMID- 15486507
TI  - Using telehealth to address the nursing shortage.
AB  - For years, government officials, health administrators, and others concerned
      about long-term care have been discussing the nursing shortage. As baby boomers
      age and fewer and fewer nurses enter the workforce, there is a growing concern
      about how to deliver health-care in the 21st Century.

PMID- 15486509
TI  - A new home health approach to swallowing disorders.
AB  - Dysphagia has devastating effects on millions of adults and children in the
      United States and contributes to the increasing cost of healthcare because of the
      aspiration that results. A new treatment, Vital-Stim, is a form of electrical
      stimulation that speech therapists can administer in the home care setting. This
      article reflects one agency's success in changing people's lives by helping them
      swallow again.

PMID- 15486511
TI  - Tracer methodology and the new Joint Commission home care and hospice survey
      process: part 1.

PMID- 15486512
TI  - Home telehealth business planning and cost analysis.

PMID- 15486513
TI  - Managing congestive heart failure using home telehealth.
AB  - Congestive heart failure (CHF) is the leading cause of rehospitalization and loss
      of revenue for home care agencies and hospitals. This article outlines how an
      agency used telehealth to provide CHF patients quality care and improved outcomes
      while decreasing the number of skilled home nursing visits and reducing
      rehospitalization rates to 1.2%.

PMID- 15486514
TI  - VNAA urges tetanus and diphtheria prevention through Spanish-language outreach.

PMID- 15486515
TI  - Selecting home telehealth staff: ten ingredients for predicting success.

PMID- 15486516
TI  - Rivastigmine augmentation in the management of chronic schizophrenia with
      comorbid dementia: an open-label study investigating effects on cognition,
      behaviour and activities of daily living.
AB  - Comorbid schizophrenia and dementia is becoming an increasingly common
      phenomenon. Because rivastigmine, a reversible acetylcholinesterase inhibitor,
      appears to delay the progression of Alzheimer's disease, it may also improve or
      delay the cognitive and behavioural disturbances evident in elderly chronic
      schizophrenia patients with comorbid cognitive decline. The aim of this study was
      to investigate augmentative rivastigmine administration in this population and to
      determine any effect on cognition, behaviour and 'activity of daily living'
      (ADLs) capabilities. Thirteen subjects with comorbid schizophrenia and dementia
      were administered open-label oral rivastigmine (9 mg/day) for a period of 12
      weeks. The results indicated improvement in Mini-Mental State Examination scores
      (P<0.01), Alzheimer's Disease Assessment Scale-cognitive subscale scores
      (P<0.001), ADL scores (P<0.01) and Positive and Negative Syndrome Scale scores
      (P<0.01). Study observations indicate beneficial effects of rivastigmine
      administration in this subpopulation of schizophrenia patients. Following on from
      other studies of cholinesterase inhibitor agents, clinical improvement in this
      patient subpopulation may extend to the class of cholinesterase inhibitor agents
      in general and not necessarily be a specific effect of any of the medications.
      The effects noted may be specific to the subpopulation of comorbid schizophrenia
      and dementia rather than schizophrenia in general. Although speculative, these
      effects may be related to cholinergic dysfunction, which has been hypothesized to
      be present in some patients with schizophrenia.

PMID- 15486517
TI  - Heart rate variability during sleep in patients with schizophrenia treated with
      olanzapine.
AB  - Cardiac adverse events in patients treated with atypical antipsychotics have
      gained increasing interest in recent years. In the present study, heart rate
      variability (HRV), which is a sensitive parameter reflecting central autonomic
      cardiac control, was investigated during treatment with olanzapine. Ten
      physically healthy male patients with schizophrenia, who displayed predominantly
      negative symptoms, were studied in the sleep laboratory under drug-free baseline
      conditions and after 4 weeks of olanzapine medication. HRV was assessed during
      different sleep stages both in the time and frequency domains. Only slight
      changes in HRV were shown during treatment, and appeared to be independent of
      sleep stages. Spectral analysis indicated a slight shift of the sympathovagal
      balance in favour of the sympathetic tone, which was consistent with an elevation
      of heart rate in the time domain; total HRV was not altered. These changes are in
      accordance with olanzapine's receptor profile exerting anticholinergic and anti
      adrenergic properties. In conclusion, taken together with findings from previous
      studies demonstrating that olanzapine does not cause clinically significant
      changes of the QTc interval, the present results are consistent with the known
      cardiac safety profile of olanzapine.

PMID- 15486518
TI  - Remission rates with venlafaxine extended release in Greek outpatients with
      generalized anxiety disorder. A double-blind, randomized, placebo controlled
      study.
AB  - The primary endpoints in this study were the remission rates [final Hamilton
      Rating Scale for Anxiety (HAM-A) total score < or =7] and reduction from baseline
      in the HAM-A total score in patients with generalized anxiety disorder (GAD) and
      no associated depression. Patients with GAD (DSM-IV and HAM-A total score >18)
      were randomly assigned to treatment with venlafaxine XR or placebo for 8 weeks. A
      1-week placebo run-in period preceded the double-blind phase. Patients with a
      >20% drop in their total HAM-A score during the run-in period, were excluded from
      the double-blind phase. All patients started therapy with 75 mg/day venlafaxine
      XR or matched placebo. Patients with less than 30% decrease in their HAM-A total
      score at the end of the second week, doubled their dose. Patients on the 150
      mg/day dose underwent a 1-week taper period. Of the 24 patients in the
      venlafaxine XR group, 62.5% achieved remission versus 9.1% in the placebo group
      (P=0.0006). The mean decrease from baseline in HAM-A total score was 19.2 points
      for the venlafaxine XR group and 10.8 points for the placebo group (P<0.001).
      Eleven placebo-treated patients and seven venlafaxine XR treated patients doubled
      their dose at the end of the second week of double-blind treatment. No patient
      interrupted therapy because of side-effects. No changes in systolic or diastolic
      blood pressure were observed. Venlafaxine XR 75-150 mg/day was well tolerated.
      The remission rates achieved with venlafaxine 75-150 mg/day in non-depressed GAD
      patients were high with good tolerability.

PMID- 15486519
TI  - Neuroprotection in Huntington's disease: a 2-year study on minocycline.
AB  - Huntington's disease (HD), a relentlessly progressive neurodegenerative disorder,
      is characterized by a clinical triad of psychiatric, cognitive and motor
      disturbances. The antibiotic minocycline, a caspase inhibitor exhibiting
      antiapoptotic properties, has been shown to prolong survival in the transgenic
      mouse model of HD. We administrated minocycline to 14 patients with genetically
      confirmed HD. The patients were psychiatrically, neurologically and
      neuropsychologically evaluated at baseline, and after 6 and 24 months of
      treatment, using the Unified HD Rating Scale and a neuropsychological test
      battery. After 12 months, three patients were lost to follow-up so that 11
      patients were analysed at the endpoint. Minocycline was well tolerated. Unlike
      the expected natural course of HD, patients exhibited stabilization in general
      motor and neuropsychological function at endpoint, after improving in the first 6
      months. Moreover, we found a significant amelioration of psychiatric symptoms
      that was not apparent after the first 6 months. In detail, the Mini-Mental State
      Examination, the Total Motor Score, the Total Functional Capacity Scale and the
      Independence Scale, as the most prominent scales in HD, were stabilized after 3
      years of treatment. Our results confirm previous animal studies and indicate a
      neuroprotective effect of this agent in HD. A long-term, double-blind, placebo
      controlled trial appears highly warranted for definitively establishing the value
      of minocycline in HD.

PMID- 15486520
TI  - Controlled comparison of two different doses of milnacipran in major depressive
      outpatients.
AB  - We compared the antidepressant efficacy and patient tolerance of two different
      doses of milnacipran (75 mg and 150 mg daily) in 66 outpatients with major
      depression, using the 17-item Hamilton Depression Rating Scale (HDRS). Only new
      patients who had never experienced frank depressive episodes before, or those who
      had remained free from thymoregulators for more than 1 year without recurrence of
      depressive symptoms, were recruited. Subjects were randomly selected to receive a
      daily dose of milnacipran that reached either 75 mg or 150 mg within 2-3 weeks
      and then remained stable over an 8-week period. The results showed a significant
      superiority of milnacipran at 150 mg/day over 75 mg/day at the end of the study
      period in both response (50% or more decrease in total score from baseline,
      P=0.026) and remission (total HDRS score lower than 7 points, P=0.034). A
      response was recorded for 56.0% of the patients treated with 75 mg of milnacipran
      and for 84.6% of those treated with 150 mg after the 8-week study period. No
      significant difference was seen between the treatment groups for either
      individual or total incidence of adverse events. Notably, nausea and vomiting
      occurred most often immediately after the first visit, when subjects in both
      groups started with a daily dose of 50 mg. We conclude that additional
      comparisons between different doses of milnacipran should be performed to confirm
      or deny the linear dose/efficacy relationship observed in the present study.

PMID- 15486521
TI  - Antipsychotic drug prescribing in the elderly is cause for concern.
AB  - Despite most studies of antipsychotic efficacy and safety having been conducted
      in young patients with schizophrenia, antipsychotic agents are often prescribed
      in elderly subjects with psychotic symptoms. The aim of this study was to
      document and describe the level of antipsychotic exposure among elderly subjects.
      We used the Regional Administrative Database of Lombardy, a region of northern
      Italy with more than 1.6 million elderly inhabitants, to extract all
      antipsychotic prescriptions dispensed during 2001 to subjects aged 65 years or
      above. Prevalence data were calculated by dividing antipsychotic users by the
      total number of male and female residents in each age group. During the 12 months
      surveyed 35 363 subjects received at least one antipsychotic prescription,
      yielding a prevalence of use of 2.18 subjects per 100 inhabitants (95% confidence
      interval 2.16-2.20). Almost two-thirds were prescribed first-generation agents
      only, and thioridazine, a first-generation agent associated with prolonged QTC
      interval, and which is restricted in most European countries, was the most
      prescribed agent. However, risperidone and olanzapine accounted for 30% of
      antipsychotic use for all subjects. The majority of patients were also prescribed
      agents for medical disorders. Because the population of Lombardy is approximately
      one-sixth of the entire Italian population, it can be assumed that there are over
      200 000 elderly subjects annually exposed to these agents in Italy. This
      generates particular concern because elderly patients are vulnerable to the
      adverse effects of antipsychotics, and recent warnings have indicated that there
      are cerebrovascular risks associated with risperidone and olanzapine therapy.

PMID- 15486522
TI  - Aripiprazole and neuroleptic malignant syndrome.
AB  - Aripiprazole, an atypical antipsychotic with a novel method of action, has only
      recently been awarded a license in the UK. We report our first patient to receive
      this drug, who had treatment-resistant schizophrenia and developed neuroleptic
      malignant syndrome (NMS) with aripiprazole. To our knowledge, this is the first
      published case report involving aripiprazole and NMS in a potentially fatal
      medical emergency. Further experience with this drug should indicate whether this
      is an isolated case (as described with other atypical antipsychotics) or
      constitutes a more serious risk than that suggested by the relatively beneficial
      therapeutic profile described in the literature to date.

PMID- 15486523
TI  - Treatment of typical Charles Bonnet syndrome with donepezil.
AB  - Charles Bonnet syndrome (CBS) is characterized by the presence of complex visual
      hallucinations in psychologically normal people. Although visual hallucinations
      in the elderly are often associated with dementia with Lewy body (DLB),
      Alzheimer's disease and delirium, they are excluded from the diagnosis of typical
      CBS, as are cognitive or psychiatric disturbances, sleep disorders and focal
      neurological lesions. Here, we describe a patient with typical CBS, who responded
      to donepezil, a cholinesterase inhibitor, and has not shown any symptoms
      suggestive of Alzheimer's disease or DLB for approximately the past 40 months.
      However, follow-up examination of her clinical symptoms is necessary for a
      definite exclusion of Alzheimer's disease and DLB. The effectiveness of donepezil
      indicates that the patient's visual hallucinations might be related to
      dysfunction of cholinergic neurones, although she did not exhibit any cognitive
      decline, or morphological and physiological brain pathology. Because donepezil
      has fewer adverse effects than anticonvulsants and neuroleptic drugs, it may be a
      safer option for the treatment of CBS in the elderly.

PMID- 15486524
TI  - The potential contribution of a computer-aided detection system for lung nodule
      detection in multidetector row computed tomography.
AB  - RATIONALE AND OBJECTIVES: We sought to evaluate the potential benefits of a
      computer-aided detection (CAD) system for detecting lung nodules in multidetector
      row CT (MDCT) scans. METHODS: A CAD system was developed for detecting lung
      nodules on MDCT scans and was applied to the data obtained from 15 patients. Two
      chest radiologists in consensus established the reference standard. The nodules
      were categorized according to their size and their relationship to the
      surrounding structures (nodule type). The differences in the sensitivities
      between an experienced chest radiologist and a CAD system without user
      interaction were evaluated using a chi2 analysis. The differences in the
      sensitivities also were compared in terms of the nodule size and the nodule type.
      RESULTS: A total of 309 nodules were identified as the reference standard. The
      sensitivity of a CAD system (81%) was not significantly different from that of a
      radiologist (85%; P > 0.05). The sensitivities of the CAD system for detecting
      nodules < or = 5 mm in diameter as well as detecting isolated nodules were higher
      than those of a radiologist (83% vs. 75%, P > 0.05; 93% vs. 76%, P < 0.001). The
      sensitivities of a radiologist for detecting nodules >5 mm and the nodules
      attached to other structures were higher than those of a CAD system (98% vs. 79%,
      P < 0.001; 91% vs. 71%, P < 0.001). There were 28.8 false-positive results of CAD
      per CT study. CONCLUSION: The CAD system developed in this study performed the
      nodule detection task in different ways to that of a radiologist in terms of the
      nodule size and the nodule type, which suggests that the CAD system can play a
      complementary role to a radiologist in detecting nodules from large CT data sets.

PMID- 15486525
TI  - Use of a nonmetallic guide wire for magnetic resonance-guided coronary artery
      catheterization.
AB  - RATIONALE AND OBJECTIVES: Metallic guide wires can be subject to substantial
      heating when used in the magnetic resonance (MR) environment. Therefore, animal
      experiments were performed to test the feasibility of a non-metallic and MR-safe
      guide wire with passive markers for catheterization of coronary arteries under MR
      guidance. MATERIALS AND METHODS: Self-made guide wires consisting of a resin
      microparticle compound covered by polytetrafluoroethylene were used to
      catheterize both coronary arteries of swine together with a non-braided catheter.
      Time needed for catheterization was recorded. RESULTS: MR-guided coronary artery
      catheterization with passive visualization of a self-made non-metallic guide wire
      is possible. In average 141 seconds (SD 68) were needed to manipulate the guide
      wire together with a catheter from the carotid artery into the left or right
      coronary artery ostium. CONCLUSION: Standard nitinol guide wires have to be
      considered unsafe for MR-guided interventions due to possible heating of
      electrical conducting structures in the MR environment. Passive visualization
      techniques allow MR-guided catheterization of small arteries like coronaries.
      However, there is the substantial disadvantage of obscuring the underlying
      anatomy of small vessels by the passive markers needed for real-time MR guidance.

PMID- 15486526
TI  - Monitoring tissue coagulation during thermoablative treatment by using a novel
      magnetic resonance imaging contrast agent.
AB  - INTRODUCTION: We tested the feasibility of using a novel contrast agent, MS-325,
      as a marker of coagulating tissue during thermoablative treatment. MATERIALS AND
      METHODS: In vivo, we created coagulated lesions in porcine muscle tissue under 3
      different conditions: MS-325 (n = 5), gadolinium-DTPA (n = 5), or no contrast
      agent (n = 9) present during laser thermoablation. At the same time, we performed
      continuous T1-weighted magnetic resonance imaging at 1.5 T. We quantified the
      change in signal intensity during treatment expressed as relative enhancement,
      and compared the 3 groups by using Mann-Whitney analysis. RESULTS: MS-325
      resulted in a more than 3.2-fold increase in relative enhancement over the
      gadolinium-DTPA and noncontrast control groups (P < 0.008). CONCLUSION: MS-325
      appears to be a valid marker for coagulating tissue and significantly increased
      relative enhancement of the treated lesions when compared with both Gd-DTPA and
      noncontrast-enhanced conditions. MS-325 thus has potential for monitoring of
      thermoablative treatment.

PMID- 15486527
TI  - Decrease of signal intensity of myometrium and cervical stroma after ultrasmall
      superparamagnetic iron oxide (USPIO) particles administration: an MR finding with
      potential benefits in T staging of uterine neoplasms.
AB  - OBJECTIVES: Following the empiric observation of a significant decrease of signal
      intensity of both myometrium and cervical stroma on ultrasmall superparamagnetic
      iron oxide (USPIO)-enhanced images, the aim of our study was to evaluate whether
      USPIO-enhanced T2*-weighted gradient echo (GRE) images might provide any
      potential advantage on T-staging of uterine malignancies having surgery and
      histology as standard of reference MATERIALS AND METHODS: Seventeen female
      patients with known uterine malignancies underwent magnetic resonance (MR)
      imaging before and 24 hours after the intravenous administration of the USPIO
      agent. Imaging protocol included proton density-weighted turbo spin echo and T2*
      weighted GRE sequences. Each patient underwent surgery within 14 days from the
      first MR examination, and histologic confirmation of tumor T-stage was obtained.
      Quantitative (calculation of signal-to-noise and contrast-to-noise ratios) and
      qualitative (visual assessment of T staging) analyses were performed on
      unenhanced and USPIO-enhanced images. RESULTS: Quantitative analysis showed a
      significantly lower (P < 0.05) signal-to-noise ratio of myometrium and cervical
      stroma on USPIO-enhanced compared with unenhanced images. In 15 of 17 patients
      (88.2%), the contrast-to-noise ratio between tumor and myometrium and between
      tumor and cervical stroma was higher on USPIO-enhanced compared with unenhanced
      images (P < 0.001). Qualitative analysis demonstrated that the GRE T2* USPIO
      enhanced MR offers a better definition of the depth of tumor infiltration rather
      than the unenhanced GRE T2* images. CONCLUSION: The decrease of signal intensity
      of myometrium and cervical stroma on T2*-weighted GRE images after the
      intravenous administration of USPIO should be considered a constant and
      physiologic finding that improves tumor conspicuity in the majority of the cases,
      allowing more accurate T-staging of neoplastic lesions.

PMID- 15486528
TI  - Initial experience of 3 tesla endorectal coil magnetic resonance imaging and 1H
      spectroscopic imaging of the prostate.
AB  - RATIONALE AND OBJECTIVES: We sought to explore the feasibility of magnetic
      resonance imaging (MRI) of the prostate at 3T, with the knowledge of potential
      drawbacks of MRI at high field strengths. MATERIAL AND METHOD: MRI, dynamic MRI,
      and 1H-MR spectroscopic imaging were performed in 10 patients with prostate
      cancer on 1.5T and 3T whole-body scanners. Comparable scan protocols were used,
      and additional high-resolution measurements at 3T were acquired. For both field
      strengths the signal-to-noise ratio was calculated and image quality was
      assessed. RESULT: At 3T the signal-to-noise ratio improved. This resulted in
      increased spatial MRI resolution, which significantly improved anatomic detail.
      The increased spectral resolution improved the separation of individual
      resonances in MRSI. Contrast-enhanced time-concentration curves could be obtained
      with a doubled temporal resolution. CONCLUSIONS: Initial results of endorectal 3T
      1H-MR spectroscopic imaging in prostate cancer patients showed potential
      advantages: the increase in spatial, temporal, and spectral resolution at higher
      field strength may result in an improved accuracy in delineating and staging
      prostate cancer.

PMID- 15486529
TI  - Optimization and standardization of lung densitometry in the assessment of
      pulmonary emphysema.
AB  - Currently, lung densitometry for the assessment of pulmonary emphysema has been
      fully validated against pathology, pulmonary function, and health status, and it
      is therefore being applied in pharmacotherapeutic trials. Nevertheless, its
      application for the early detection of emphysema has not yet been introduced in
      daily clinical practice. The main reason for this is the fact that it is not yet
      regarded a fully optimized and standardized technique. In this work, an overview
      is given on the current status of different standardization aspects that play an
      important role in this, ie, image acquisition, choice of densitometric parameter
      and image processing. To address these issues, solutions have been sought from
      the literature and from original data from previous studies. Standardization and
      optimization of lung densitometry has reached a more advanced stage than has been
      reported so far. If normal values will become available, this technique will be
      feasible for clinical practice. As a result, standardization for the detection
      and assessment of other density-related lung diseases can be achieved in a
      shorter period of time.

PMID- 15486530
TI  - Percutaneous radiofrequency ablation of hepatic colorectal metastases: technique,
      indications, results, and new promises.
AB  - Surgical resection is the standard of care for colorectal metastases isolated to
      the liver. However, only 10-25% of the patients are eligible for resection
      because of extent and location of the disease in the liver or concurrent medical
      conditions. Image-guided radiofrequency (RF) ablation is a minimally invasive
      technique that is emerging as a viable alternate treatment of nonsurgical
      patients with limited hepatic metastatic disease. Several series have shown that
      RF ablation can result in complete tumor eradication in properly selected
      candidates and have provided indirect evidence that the treatment improves
      survival. In a recent multicenter trial including 423 patients, overall survival
      of RF-ablation treated patients reached 47% at 3 years and 24% at 5 years. RF
      ablation technology is undergoing continuous improvement, and its clinical
      application has been successfully expanded to the treatment of colorectal
      metastases to the lung. Randomized trials comparing RF ablation with either
      surgical resection or chemotherapy protocols, however, are still missing. In this
      article, we review technique, indications, clinical results, and future prospects
      of RF ablation in the therapeutic management of metastatic colorectal cancer
      patients.

PMID- 15486531
TI  - Renal disease: value of functional magnetic resonance imaging with flow and
      perfusion measurements.
AB  - PURPOSE: To differentiate healthy kidneys from diseased kidneys, we propose a
      combined magnetic resonance (MR) examination that includes measurements of renal
      arterial blood flow and parenchymal perfusion. MATERIALS AND METHODS: A total of
      130 kidneys (patients/healthy volunteers: 83/47) were examined using renal artery
      MR flow measurements and renal parenchymal perfusion measurements, as well as
      contrast-enhanced MR angiography. Cine phase-contrast-flow measurements were
      performed using an ECG-gated fast low angle shot pulse sequence; perfusion was
      measured with an arterial spin labeling flow-sensitive alternating inversion
      recovery technique. Contrast-enhanced MR angiography was performed with a fast 3D
      gradient echo sequence in a single breath hold. For evaluation, kidneys were
      divided into groups based on nephrologic diagnosis of the patient. Recursive
      partitioning and Wilcoxon rank-sum tests were used to separate the different
      groups. RESULTS: Significant differences in mean renal artery flow and
      parenchymal perfusion were found in kidneys with renal artery stenosis as well as
      parenchymal disease as compared with healthy kidneys. Using a classification tree
      derived from the recursive partitioning, a specificity of 99% and sensitivity of
      69% with a positive/negative predictive value of 97%/84% was achieved for the
      separation of healthy kidneys from kidneys with vascular, parenchymal or combined
      disease. The overall accuracy was 88%. CONCLUSION: The combination of cine PC
      flow measurements and MR perfusion measurements offers a comprehensive assessment
      of both renovascular and renoparenchymal disease and provide a noninvasive
      approach to differentiate between these kidneys and normal kidneys.

PMID- 15486532
TI  - Discriminatory ability of magnetic resonance T2* measurements in a sample of
      postmenopausal women with low-energy fractures: a comparison with phalangeal
      speed of sound and dual x-ray absorptiometry.
AB  - RATIONALE AND OBJECTIVES: We sought to assess the ability of magnetic resonance
      T2* measurements to discriminate between patients with and without osteoporotic
      fracture and compare the results with the discriminatory ability of speed of
      sound (SOS) measured at the phalanx and axial bone mineral density (BMD).
      MATERIALS AND METHODS: T2* measurements of lumbar spine were obtained at 1.5 T in
      26 postmenopausal women with osteoporotic fractures and 28 age-matched healthy
      control subjects. A multiecho gradient echo (MEGRE) pulse train sequence was used
      with echo times of 2.70-74.93 milliseconds using 2.33-millisecond interecho
      intervals. BMD measurements were made in the axial skeleton. SOS also was
      measured at the finger phalanges. RESULTS: The in vivo short-term reproducibility
      for T2* was 1.85%. T2*, spinal BMD, total hip BMD, and SOS measurements were
      found to give comparable discrimination between normal and osteoporotic women
      with odds ratios of 2.6, 2.6, 3.2, and 2.2, respectively. CONCLUSIONS: T2*
      measurements of lumbar spine are reproducible and capable of differentiating
      between postmenopausal women with and those without osteoporotic fractures.

PMID- 15486534
TI  - Coagulation in sepsis.
AB  - Activation of the coagulation cascade during invasive infection can result in
      purpura fulminans, with rapid progression of tissue ischemia, or may manifest as
      abnormal clotting indices alone. Although severe derangements in coagulation are
      associated with organ dysfunction and increased mortality, the contribution of
      coagulopathy to the pathophysiology of sepsis remains incompletely understood.
      Over the past decade, investigators have evaluated several therapeutic
      anticoagulant strategies in sepsis, and manipulation of the coagulation system
      has emerged as a key concept in the current management of this disease. Clinical
      observations during treatment of septic patients with the endogenous
      anticoagulant activated protein C have stimulated additional study of
      interactions between endothelial injury, coagulation, and inflammation. This
      review describes clotting abnormalities during sepsis and discusses the clinical
      experience with therapeutic strategies intended to oppose excessive coagulation.

PMID- 15486533
TI  - Severe sepsis: new concepts in pathogenesis and management.

PMID- 15486535
TI  - Drotrecogin alfa (activated) for the treatment of severe sepsis and septic shock.
AB  - Coagulopathy and systemic inflammation are almost universal in patients with
      severe sepsis. Interaction between the two results in an intense inflammatory
      response and microthrombi formation in the vessels of multiple organs, resulting
      in organ dysfunction or severe sepsis. Recombinant human activated protein C,
      also known as drotrecogin alfa (activated), possesses anti-inflammatory,
      antithrombotic, and profibrinolytic properties. Treatment with drotrecogin alfa
      (activated) significantly reduces morbidity and mortality in patients with severe
      sepsis. An increased risk of bleeding during the infusion was the only side
      effect experienced. Recent data demonstrate that early administration of
      drotrecogin alfa (activated) is associated with lower mortality rates. Despite
      concern over its relatively high cost, analysis has demonstrated that recombinant
      human activated protein C is as cost-effective as other commonly used treatments
      in the intensive care unit.

PMID- 15486537
TI  - Dysregulation of the immune response in severe sepsis.
AB  - Sepsis is systemic expression of a generalized activation of the host's innate
      immunity as a result of varied types of insults. This expression involves a
      cellular inflammatory response that has both proinflammatory and antiinflammatory
      components, the primary trigger for which is an intracellular oxidative stress,
      induced by receptor-mediated transmembrane signal transduction or direct noxious
      injury. Sepsis reflects the interaction between pro- and anti-inflammatory
      intracellular mechanisms, the uncontrolled activation of which leads to cell
      exhaustion, organ dysfunction, and death. Successful clinical trials of novel
      treatments for the management of severe sepsis share a common ability to down
      regulate this overall response, restoring normal proinflammatory responsiveness
      and mitochondrial energetic function.

PMID- 15486536
TI  - Recombinant human activated protein C in sepsis: assessing its clinical use.
AB  - Based on the results of the phase III PROWESS trial, recombinant human activated
      protein C (rhAPC) was approved by the Food and Drug Administration (FDA) for use
      in severely septic patients. Concerns regarding rhAPC's inconsistent effects,
      incomplete understanding of its mechanism of action, and its safety in particular
      subgroups were raised during the FDA's evaluation. This study attempts to assess
      the cost-effectiveness rhAPC by comparing its effects during recent clinical use
      to its prior phase III trial testing and by considering other potentially less
      expensive treatments with effects that may overlap those of rhAPC. In patients
      with similar numbers of injured organs, mortality rates may be higher with rhAPC
      during clinical use compared with the phase III trial. There may also be an
      increased risk of hemorrhage and other adverse events that necessitate early
      discontinuation of treatment. Many of the patients receiving rhAPC during
      clinical use may have otherwise been excluded from its phase III trial testing.
      Data from several recent phase III trials as well as a recent meta-analysis
      suggest that heparin and physiologic dose steroids offer substantially less
      expensive alternatives to rhAPC. Further phase IV testing will be required to
      confirm such possibilities.

PMID- 15486538
TI  - The lung in sepsis: fueling the fire.
AB  - Advances in our understanding of the molecular mechanisms underlying the
      pathophysiology of sepsis have generated considerable efforts in manipulating the
      host response during this frequently lethal condition. While existing trials of
      immune modulation have been largely unsuccessful, an appreciation for the roles
      of individual organ systems in sepsis is important to enable clinicians to
      discern how each functions as both a target for injury and a contributor to the
      derangement in homeostasis seen in sepsis. Such awareness will encourage
      treatment decisions aimed at optimizing conventional therapy while minimizing the
      adverse effects of supportive care, and it may also guide the incorporation of
      newer immunomodulatory therapeutics into our existing modalities. This article
      discusses the lung's response to sepsis, from the standpoint of organ dysfunction
      related to sepsis as well as its participation in the generation and maintenance
      of the systemic inflammatory state.

PMID- 15486539
TI  - The endocrine system during sepsis.
AB  - Endocrinopathy during sepsis can manifest as hyperglycemia and insulin resistance
      or as insufficient production of either adrenal corticosteroids or vasopressin.
      The results of a recent large clinical trial have demonstrated that tight
      glycemic control with insulin can confer survival benefit to selected intensive
      care unit patients. Relative impairment of adrenocortical reserve has been
      suggested to be an important contributor to the pathogenesis of shock in sepsis.
      Replacement doses of glucocorticoids and mineralocorticoids have been associated
      with improved survival in the subset of patients with blunted results on
      adrenocorticotropin hormone stimulation tests. Posterior pituitary production of
      vasopressin is diminished in septic shock while sensitivity to its vasopressor
      effects is enhanced. Clinical trials are underway to determine whether
      administration of vasopressin can improve outcomes in patients with septic shock.
      Whether the euthyroid sick syndrome represents an adaptive or a maladaptive
      response to severe illness remains unclear.

PMID- 15486542
TI  - A daughter's journey promoting geriatric self-care: promoting positive health
      care interactions.
AB  - Love for my parents leads me to promoting geriatric self-care. Methods of
      empowerment, identification of barriers and methods of overcoming them, and tools
      for the health care provider in promoting positive health care interactions is
      the focus of this article. When the older adult and the health care provider work
      together, the barrier of knowledge regarding chronic conditions is more likely to
      be overcome, allowing for the best alternatives in assessment, medication,
      treatment, and referral. Beginning with the material available from the National
      Institute of Aging (NIA) Web site, both the older adult and health care provider
      can promote positive health care interactions. Care and concern for the older
      adult is needed by all in the health care field. We are the older adults of
      tomorrow.

PMID- 15486543
TI  - Enhancing self-care in community dwelling older adults.
AB  - This article describes the development of an enrichment program to promote social
      support, coping with aging, and enhancing self-care in a sample of African
      American older adults living independently in low-income public housing. To
      address the needs of the increasing population of older adults in the United
      States, health initiatives that foster independence, wellness, and self-care are
      essential.

PMID- 15486544
TI  - Old is a three-letter word.
AB  - Even the most experienced gerontological nurse can learn a few things from the
      knowledge gleaned first hand by an aging professional who suffered a stroke and
      endured the long come-back through therapy. This anecdotal article provides a
      different viewpoint for those entrusted with the care of the elderly and provides
      tips for effectively dealing with some of the more prevalent problems nurses face
      when working with old people.

PMID- 15486545
TI  - Using computers to reduce medication misuse of community-based seniors: results
      of a pilot intervention program.
AB  - Persons over the age of 65 are at high risk for conditions related to medication
      misuse. Addressing this issue is important to prevent serious outcomes such as
      falls, drug interactions, rehospitalization, and addiction. The role of community
      based organizations, such as senior centers, in preventing medication misuse can
      be enhanced by the use of standardized interventions. This article reports a
      pilot project implementing laptop computer interventions for medication misuse by
      seniors. The study was conducted in Cleveland, Ohio, with 412 seniors
      participating in Area Agency on Aging programs. Seniors completed a computerized
      simple screening for medication misuse and watched short video clips related to
      their own potential misuse. Seniors also received a medication reminder checklist
      and a 7-day pill-dispensing box. Results of a 2-month follow-up interview
      revealed promising results, with 55% of participants using the medication
      reminder checklist. One-third of participants visited their doctor to discuss the
      medication misuse feedback. Almost all of the participants found the computerized
      administration of the intervention to be easy and helpful. The study supports the
      further development of community-based interventions for seniors using
      computerized administration.

PMID- 15486546
TI  - Music preference and relaxation in Taiwanese elderly people.
AB  - The purpose of this study was to identify individual musical preferences,
      investigate the relationship between an individual's musical preferences and
      demographic variables, and examine the effects of the selected music on
      relaxation. Fifty healthy subjects (mean age 65.7; SD = 5.2) from the community
      participated in the study. Musical preference interviews and relaxed responses to
      selected music were administered to the study participants individually in the
      investigator's office. Participants' heart rates, respiratory rates, and finger
      temperature were measured before they listened to the introductory tape and again
      after they listened to the selected music for 20 minutes. The participants were
      asked to judge how much they liked the 6 types of soothing music and were asked
      to rate it on a scale. The results indicated that Chinese orchestral music was
      the preferred choice, followed by harp, piano, synthesizer, orchestral, and
      finally slow jazz. There were no differences among types of music on relaxation,
      and no significant differences between musical preference and any demographic
      variables. The heart rates and respiratory rates of the participants were
      significantly lower (t = 21.24, P < .001 and t = 20.09, P < .001, respectively).
      Finger temperature (t = -33.20, P < .001) raised significantly after listening to
      the selected music. These findings suggest that soothing music selections have
      beneficial effects on relaxation in community-residing elderly people.

PMID- 15486547
TI  - Testing of the Res-Care Pilot Intervention: Impact on nursing assistants.
AB  - The purpose of this study was to test the feasibility and effectiveness of a two
      tiered motivational intervention--the Res-Care Pilot Intervention--on willingness
      of nursing assistants to participate in the Res-Care Intervention, the impact of
      the intervention on nursing assistants' self-efficacy, and outcome expectations
      related to restorative care, knowledge of restorative care, restorative care
      behaviors, and job satisfaction. A sample of 13 nursing assistants with an
      average age of 47.3 +/- 8.9 (range 29-56) years, the majority of whom were women
      (93%) and African American (77%), consented to participate in the study. There
      was a statistically significant increase in outcome expectations related to
      restorative care activities (F = 8.9, P <.05), a nonsignificant trend toward
      increased knowledge of restorative care (F = 1.4, P > .05) and documented time
      doing restorative care activities (F = -.56, P > .05), and no difference in self
      efficacy expectations (F = .58, P > .05) or job satisfaction (F = .48, P > .05).
      The findings provide useful information for future research in restorative care.

PMID- 15486549
TI  - Development of a healthy bladder education program for older adults.
AB  - The Healthy Bladder Program was developed as part of an academic and health care
      partnership and was designed specifically for older adults residing in
      independent and assisted living. Program content was based on best practices that
      can be used by nursing staff to provide information about promoting and
      maintaining bladder health. One hundred eighty older adults, recruited from long
      term care retirement communities, attended the 1-hour program. Findings showed
      that the program was successful in providing bladder health information that
      older adults could use immediately; suggestions are given for best practice
      applications.

PMID- 15486550
TI  - Resources for dietary self-management of diabetes.

PMID- 15486551
TI  - Research review: Self-administration of medication in hospital: patients'
      perspectives.

PMID- 15486553
TI  - Gerontologic nurse practitioner care guidelines: sleep management in elderly
      patients.

PMID- 15486554
TI  - Chronic illness demands for self-management in older adults.

PMID- 15486555
TI  - Teaching older adults medication self-care.

PMID- 15486556
TI  - Suppression of peritoneal implantation of gastric cancer cells by adenovirus
      vector-mediated NK4 expression.
AB  - Peritoneal dissemination is the most common mode of metastasis in gastric cancer.
      We previously reported the importance of milky spots (MS), peritoneal lymphoid
      tissues, as selective sites of cancer implantation in peritoneal dissemination.
      In the present study, we first demonstrated that intraperitoneal injection of
      adenovirus vector encoding the GFP gene into tumor-free nude mice resulted in GFP
      expression at omental and mesenteric MS; MS macrophages were target cells for
      adenovirus infection. We confirmed that intraperitoneal injection of adenovirus
      vector encoding the NK4 gene (AdNK4) resulted in NK4 production localized to the
      peritoneal cavity, especially the omentum. Adenovirus vector-mediated MS
      selective transgene expression was markedly impaired in tumor-bearing mice whose
      MS had already been replaced by infiltrating cancer cells. However, prior
      injection of AdNK4 successfully inhibited MS-selective cancer cell implantation,
      resulting in suppression of peritoneal dissemination and prolongation of
      survival. Adenovirus vector-mediated MS-selective delivery of a therapeutic gene
      may prevent peritoneal dissemination of gastric cancer.

PMID- 15486557
TI  - Suppression of pancreatic tumor growth in the liver by systemic administration of
      the TRAIL gene driven by the hTERT promoter.
AB  - Local and locoregional administration of adenovectors expressing the tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) gene has been
      demonstrated to be useful in treating established tumors in animals. Moreover,
      expression of the TRAIL gene from the human telomerase reverse transcriptase
      (hTERT) promoter can be used to prevent possible liver toxicity of the TRAIL
      gene. However, it remains unknown whether systemic administration of the TRAIL
      expressing adenovector can be used for cancer therapy. Here, we showed that a
      combination of TRAIL gene therapy and gemcitabine, the first-line chemotheraphy
      agent for pancreatic cancer, had a synergistic effect on the induction of
      apoptosis in human pancreatic cancer cell lines in vitro. Systemic administration
      of an adenovector that contains an insertion of integrin-binding motif argine
      glycine-aspartate (RGD) in the HI loop of the adenoviral fiber protein and
      expresses the human TRAIL gene from the hTERT promoter (designated Ad/TRAIL
      F/RGD) suppressed the growth of human pancreatic tumor cells inoculated in the
      liver of nu/nu nude mice. Furthermore, Ad/TRAIL-F/RGD in combination with
      gemcitabine suppressed the tumor growth of pancreatic cancer in the liver more
      than did treatments consisting of each agent alone. No obvious liver toxicity was
      detected in any of the treatment groups. Our results suggest that TRAIL gene
      therapy in combination with gemcitabine might be a useful therapeutic approach
      for treating metastatic pancreatic cancers.

PMID- 15486558
TI  - Intramuscular delivery of antiangiogenic genes suppresses secondary metastases
      after removal of primary tumors.
AB  - The success of surgery to remove primary tumors can be compromised by the
      subsequent outgrowth of metastases. It is recognized that primary tumors secrete
      antiangiogenic factors that suppress the outgrowth of their daughter metastases.
      In accord we show here that surgical removal of primary EL-4 lymphomas led to a
      marked decrease in the levels of circulating angiostatin and endostatin, and
      promoted the growth of distant nodular tumors. Expression vectors encoding
      angiostatin and endostatin, formulated with poly-N-vinyl pyrrolidone (PVP), were
      injected into the tibialis and gastrocnemia muscles, leading to expression of
      angiostatin and endostatin in muscle fibers. High levels of biologically active
      exogenous proteins were secreted into the circulation. Intramuscular gene therapy
      with angiostatin and endostatin plasmids significantly inhibited tumor
      vascularity and induced tumor cell apoptosis, and thereby suppressed the growth
      of secondary subcutaneous and disseminated metastatic tumors in the lung and
      liver. Simultaneous intramuscular delivery of both angiostatin and endostatin
      plasmids significantly prolonged the survival of mice after removal of primary
      tumors. These results suggest that intramuscular gene transfer of angiostatin and
      endostatin might serve as a prophylactic cancer-prevention strategy to combat the
      recurrence of cancer after surgical resection of primary tumors.

PMID- 15486559
TI  - Immunocompetent mouse model of breast cancer for preclinical testing of EphA2
      targeted therapy.
AB  - EphA2, a receptor tyrosine kinase, is elevated in many invasive human breast
      cancers, and the majority of EphA2 remains unphosphorylated. The successful
      attachment of ligand EphrinA1 present on the surface of adjacent cells to EphA2
      initiates EphA2 phosphorylation leading to its turnover. In vivo efficacy of
      various approaches targeting EphA2 for breast cancer therapy is usually evaluated
      in nude mice bearing human breast cancer xenografts. In order to establish an
      immunocompetent mouse model of breast cancer for EphA2-targeted therapies, we
      evaluated a mouse breast cancer cell line (MT1A2) for EphA2 expression and
      phosphorylation. Overexpression of EphA2 was observed in MT1A2 cells and the
      majority of it remained unphosphorylated signifying that EphA2 in MT1A2 cells
      behaved similar to that of human breast cancer cells. Human adenovirus subtype 5
      (HAd5) vectors expressing secretory forms of EphrinA1 were used for in vitro and
      in vivo targeting of MT1A2-derived EphA2. MT1A2 cells infected with HAd-EphrinA1
      Fc (HAd expressing extracellular domain of human EphrinA1 attached to Fc portion
      of human IgG1 heavy chain) induced EphA2 activation and its turnover. This led to
      inhibition in MT1A2 cell colony formation in soft agar and cell viability in
      monolayer culture. In addition, MT1A2 cells-infected with HAd-EphrinA1-Fc failed
      to form tumors in syngeneic FVB/n mice at least 32 days postinoculation.
      Moreover, intratumoral inoculation of FVB/n mice-bearing MT1A2-induced tumors
      with HAd-EphrinA1-Fc slowed the tumor growth and also resulted in the development
      of vector-specific immune response. These results indicate that FVB/n mice
      bearing MT1A2-induced tumors could serve as an immunocompetent model of breast
      cancer for EphA2-targeted therapeutic strategies.

PMID- 15486560
TI  - Liposomal vector mediated delivery of the 3p FUS1 gene demonstrates potent
      antitumor activity against human lung cancer in vivo.
AB  - Lung cancer is one of the leading causes of death in the world. The underlying
      cause for lung cancer has been attributed to various factors that include
      alteration and mutation in the tumor suppressor genes. Restoration of normal
      function of the tumor suppressor gene is a potential therapeutic strategy. Recent
      studies have identified a group of candidate tumor suppressor genes on human
      chromosome 3p21.3 that are frequently deleted in human lung and breast cancers.
      Among the various genes identified in the 3p21.3 region, we tested the antitumor
      activity of the FUS1 gene in two human non-small-cell lung cancer (NSCLC)
      xenografts in vivo. Intratumoral administration of FUS1 gene complexed to
      DOTAP:cholesterol (DOTAP:Chol) liposome into subcutaneous H1299 and A549 lung
      tumor xenograft resulted in significant (P = .02) inhibition of tumor growth.
      Furthermore, intravenous injections of DOTAP:Chol-FUS1 complex into mice bearing
      experimental A549 lung metastasis demonstrated significant (P = .001) decrease in
      the number of metastatic tumor nodules. Finally, lung tumor-bearing animals when
      treated with DOTAP:Chol-FUS1 complex demonstrate prolonged survival (median
      survival time: 80 days, P = .01) compared to control animals. This result
      demonstrates the potent tumor suppressive activity of the FUS1 gene and is a
      promising therapeutic agent for treatment of primary and disseminated human lung
      cancer.

PMID- 15486563
TI  - The topoisomerase 1-interacting protein BTBD1 is essential for muscle cell
      differentiation.
AB  - DNA topoisomerase I (Topo1) contributes to vital biological functions, but its
      regulation is not clearly understood. The BTBD1 protein was recently cloned on
      the basis of its interaction with the core domain of Topo1 and is expressed
      particularly in skeletal muscle. To determine BTBD1 functions in this tissue, the
      in vitro model used was the C2C12 mouse muscle cell line, which expresses BTBD1
      mainly after myotube differentiation. We studied the effects of a stably
      overexpressed BTBD1 protein truncated of the 108 N-terminal amino-acid residues
      and harbouring a C-terminal FLAG tag (Delta-BTBD1). The proliferation speed of
      Delta-BTBD1 C2C12 cells was significantly decreased and no myogenic
      differentiation was observed, although these cells maintained their capacity to
      enter adipocyte differentiation. These alterations could be related to Topo1
      deregulation. This hypothesis is further supported by the decrease in nuclear
      Topo1 content in Delta-BTBTD1 proliferative C2C12 cells and the switch from the
      main peripheral nuclear localization of Topo1 to a mainly nuclear diffuse
      localization in Delta-BTBTD1 C2C12 cells. Finally, this study demonstrated that
      BTBD1 is essential for myogenic differentiation.

PMID- 15486564
TI  - Oct4 is required for primordial germ cell survival.
AB  - Previous studies have shown that Oct4 has an essential role in maintaining
      pluripotency of cells of the inner cell mass (ICM) and embryonic stem cells.
      However, Oct4 null homozygous embryos die around the time of implantation, thus
      precluding further analysis of gene function during development. We have used the
      conditional Cre/loxP gene targeting strategy to assess Oct4 function in
      primordial germ cells (PGCs). Loss of Oct4 function leads to apoptosis of PGCs
      rather than to differentiation into a trophectodermal lineage, as has been
      described for Oct4-deficient ICM cells. These new results suggest a previously
      unknown function of Oct4 in maintaining viability of mammalian germline.

PMID- 15486566
TI  - The fly Olympics: faster, higher and stronger answers to developmental questions.
      Conference on the Molecular and Developmental Biology of Drosophila.

PMID- 15486565
TI  - A molecular basis underlying differences in the toxicity of botulinum serotypes A
      and E.
AB  - Botulinum neurotoxins (BoNTs) block neurotransmitter release through their
      specific proteolysis of the proteins responsible for vesicle exocytosis.
      Paradoxically, two serotypes of BoNTs, A and E, cleave the same molecule,
      synaptosome-associated protein with relative molecular mass 25K (SNAP-25), and
      yet they cause synaptic blockade with very different properties. Here we compared
      the action of BoNTs A and E on the plasma membrane fusion machinery composed of
      syntaxin and SNAP-25. We now show that the BoNT/A-cleaved SNAP-25 maintains its
      association with two syntaxin isoforms in vitro, which is mirrored by retention
      of SNAP-25 on the plasma membrane in vivo. In contrast, BoNT/E severely
      compromises the ability of SNAP-25 to bind the plasma membrane syntaxin isoforms,
      leading to dissociation of SNAP-25. The distinct properties of botulinum
      intoxication, therefore, can result from the ability of shortened SNAP-25 to
      maintain its association with syntaxins-in the case of BoNT/A poisoning resulting
      in unproductive syntaxin/SNAP-25 complexes that impede vesicle exocytosis.

PMID- 15486567
TI  - Patient attitudes to receiving copies of outpatient clinic letters from the
      ocular oncologist to the referring ophthalmologist and GP.
AB  - AIM: To investigate patients' views and understanding on receiving a copy of the
      outpatient clinic letter from the ocular oncologist to the referring
      ophthalmologist and GP. METHODS: Face-to-face interviews were conducted with 52
      patients attending outpatient ocular oncology follow-up clinics, in a
      semistructured format using a qualitative open-ended questionnaire. The clinics
      are held at Liverpool Ocular Oncology Centre, a tertiary specialist referral
      centre at St. Paul's Eye Unit in Royal Liverpool University Hospital. RESULTS:
      Patients' views on receiving a copy of the outpatient letter, their understanding
      of the letter, and improvements suggested. A total of 58% of patients had
      received a letter and 97% of them said they were glad they had it. Of this group
      77% had shown it to family/friend. Consistent comments included: 'help with
      accepting the news;' 'good to be informed and to know what to expect;' 'confirmed
      what was said in the consultation.' Of the patients who had not received a copy
      of the letter, 64% replied that they would have liked a copy. A total of 80% of
      patients reported that they fully understood the letter. In all, 17% wanted
      medical terms to be explained, when asked to suggest improvements. CONCLUSIONS:
      Sending patients copies of the consultant outpatient letter seemed to be highly
      appreciated and a useful method of information giving regarding diagnosis and
      management.

PMID- 15486568
TI  - Posterior scleritis mimicking orbital cellulitis.

PMID- 15486569
TI  - A randomized double-blind placebo-controlled study of the long-term efficacy and
      safety of topiramate in the treatment of obese subjects.
AB  - BACKGROUND: Treatment of obese subjects with topiramate has recently been
      associated with significant weight loss in a 6-month dose-ranging study.
      OBJECTIVE: To investigate the long-term efficacy and safety of topiramate in
      obese subjects. DESIGN: Randomised, double-blind, placebo-controlled study
      investigating three doses of topiramate: 96, 192, and 256 mg/day. All subjects
      also participated in a nonpharmacological weight-loss programme. SUBJECTS: The
      study included 1289 subjects 18-75 y with a body mass index >/=30 kg/m(2) and <50
      kg/m(2) in the absence of comorbidities, or >/=27 kg/m(2) and <50 kg/m(2) in the
      presence of controlled hypertension and/or dyslipidaemia. DURATION: The original
      study design was for a 6-week, single-blind, placebo run-in phase followed by an
      8-week titration phase and 2 y of maintenance at the assigned dose. Sponsor ended
      study early in order to develop a new controlled-release formulation with the
      potential to enhance tolerability and simplify dosing in this patient population.
      Therefore, none of the subjects completed the full 2 y of treatment. Efficacy
      results are based on subjects who were enrolled early enough to have had an
      opportunity to complete 1 y at their assigned dose (modified intent-to-treat
      population, MITT) before learning of the decision to terminate the study. Safety
      results are based on all subjects who took at least one dose of study medication.
      RESULTS: The safety population consisted of 1282 subjects, and the MITT efficacy
      population was 854 subjects. At 60 weeks, subjects in the placebo group lost 1.7%
      of their baseline body weight, while subjects in the topiramate 96, 192, and 256
      mg/day treatment groups lost 7.0, 9.1, and 9.7%, respectively (P<0.001, MITT,
      last observation carried forward). Weight loss >/=5% of baseline weight was
      achieved by 18% of subjects in the placebo arm vs 54, 61, and 67% of subjects
      receiving topiramate 96, 192, and 256 mg/day, respectively; weight loss >/=10%
      was achieved by 6 vs 29, 40, and 44%, respectively (P<0.001). Weight loss was
      accompanied by significant improvements in blood pressure (systolic/diastolic
      changes of +0.4/+1.0, -3.1/-1.3, -5.7/-3.4, and -4.6/-2.4 mmHg were observed for
      placebo, topiramate 96 mg/day, 192 mg/day, and 256 mg/day, respectively, P<0.001)
      and glucose and insulin. The most common adverse events more frequently observed
      in topiramate-treated subjects occurred mostly during the titration phase and
      were related to the central or peripheral nervous system and included
      paresthesia, difficulty with concentration/attention, depression, difficulty with
      memory, language problems, nervousness, and psychomotor slowing. CONCLUSION:
      Topiramate treatment of obese subjects over the course of 1 y resulted in
      clinically significant weight loss. Improvements were also observed in blood
      pressure and glucose tolerance.

PMID- 15486570
TI  - Relationships in women between body mass index and the intravascular metabolism
      of chylomicron-like emulsions.
AB  - OBJECTIVE: To investigate whether increasing body mass index (BMI) produces
      increasingly intense disturbances in the metabolism of chylomicrons, the
      lipoproteins that carry the dietary lipids absorbed by the intestine in the
      circulation. SUBJECTS: Four groups of 10 normolipidemic nondiabetic women at the
      normal (BMI<25 kg/m(2)), preobese (BMI 25-30), obese (BMI 30-40) and morbid obese
      (BMI>40). METHODS: Chylomicron metabolism was studied using the method of
      triglyceride-rich emulsions that mimic chylomicrons. The chylomicron-like
      emulsion doubly labeled with (3)H-triolein (TO) and (14)C-cholesteryl-oleate (CO)
      was intravenously injected to calculate the plasma fractional clearance rates
      (FCR, in min(-1)) by a compartmental analysis model. FCR-TO mirrors both the
      lipolysis from lipoprotein lipase that the emulsion suffers while still in the
      circulation, and the triglycerides portion that is not broken down and is removed
      from the plasma together with the remnant particles. Lipolysis index is
      calculated subtracting CO from TO areas under the curve. RESULTS: FCR-TO did not
      differ among the four groups. The lipolysis index was positively correlated with
      BMI (r=0.310; P=0.05). On the other hand, FCR-CO progressively diminished from
      the normal to the morbid obese group (0.069+/-0.01; 0.064+/-0.01; 0.031+/-0.003;
      0.029+/-0.005 min(-1), respectively, P=0.003) and there was a negative
      correlation between FCR-CO and BMI (r=-0.388; P=0.01). CONCLUSION: In obesity,
      the capacity to break down chylomicron triglycerides by lipoprotein lipase in
      vivo increases, but the ability of the organism to remove the resulting
      chylomicron remnants particles progressively diminishes as the BMI rises. Remnant
      accumulation most likely predisposes to coronary artery disease development.

PMID- 15486571
TI  - Breaking down the stereotypes of science by recruiting young scientists.

PMID- 15486572
TI  - Nature's nanotechnologists: unveiling the secrets of diatoms.

PMID- 15486577
TI  - Hearing: travelling wave or resonance?

PMID- 15486582
TI  - Diversifying selection in plant breeding.

PMID- 15486585
TI  - Why are so many bird flowers red?

PMID- 15486583
TI  - Skeletal muscle fiber type: influence on contractile and metabolic properties.

PMID- 15486586
TI  - Open access as public policy.

PMID- 15486594
TI  - About The Association of Medicine and Psychiatry.

PMID- 15486587
TI  - DNA barcoding: promise and pitfalls.

PMID- 15486595
TI  - We Are Dying Out Here.

PMID- 15486597
TI  - Billing for the Evaluation and Treatment of Adult Depression by the Primary Care
      Clinician.
AB  - Depression is a common problem encountered in primary care practice. There are
      many barriers that the primary care clinician faces in managing patients with
      depression. Financial reimbursement is one infrequently addressed barrier that
      influences how care is provided. This article addresses the coding,
      documentation, and reimbursement issues that pertain to the treatment of
      depression in the primary care setting. Coding options are reviewed with specific
      documentation guidelines. Reimbursement and fee schedule issues are also
      addressed, including clarification of certain limitations on payment by some
      payers.

PMID- 15486596
TI  - Sleep in the Elderly: Burden, Diagnosis, and Treatment.
AB  - Insomnia is commonly seen in elderly populations and is associated with numerous
      individual and socioeconomic consequences. Elderly patients are more likely to
      suffer from chronic insomnia characterized by difficulty maintaining sleep than
      difficulty initiating sleep. Management of insomnia in these patients requires
      very careful evaluation and exclusion of an underlying medical or psychiatric
      condition. Nonpharmacologic interventions in elderly patients, especially use of
      behavioral therapy, have demonstrated some success. Commonly prescribed
      medications have also been effective, though they have limitations. Newer agents
      currently under investigation for insomnia hold promise for good efficacy and
      safety in the elderly population. The following review presents clinical studies,
      survey results, and guidelines retrieved from peer-reviewed journals in the
      PubMed database using the search terms elderly, temazepam, trazodone, zolpidem,
      zaleplon, insomnia, and prevalence and the dates 1980 to 2003. In addition, newer
      research with emerging agents has been included for completeness.

PMID- 15486599
TI  - Effective Recognition and Treatment of Generalized Anxiety Disorder in Primary
      Care.
AB  - This Academic Highlights section of The Primary Care Companion to The Journal of
      Clinical Psychiatry presents the highlights of the planning roundtable "Effective
      Recognition and Treatment of Generalized Anxiety Disorder (GAD) in the Primary
      Care Setting," held December 11, 2003, in Pittsburgh, Pa. The planning roundtable
      and this Academic Highlights were supported by an unrestricted educational grant
      from Pfizer. The planning roundtable was chaired by Larry Culpepper, M.D.,
      M.P.H., Boston University School of Medicine, Boston, Mass. The faculty member
      was Kathryn M. Connor, M.D., Duke University Medical Center, Durham, N.C.

PMID- 15486598
TI  - Undiagnosed Bipolar Disorder: New Syndromes and New Treatments.
AB  - Recent studies have indicated that bipolar disorder is more common than
      previously believed. The socioeconomic and personal burdens of this illness are
      significant, and the lifetime risk of suicide attempts by patients with bipolar
      II disorder is high. It is not uncommon for patients with bipolar disorder,
      especially those presenting with depression, to be seen first in a primary care
      setting; therefore, primary care physicians need to be ready to diagnose and
      manage patients with these mental illnesses. The diagnosis of bipolar disorder or
      bipolar spectrum disorder is easily missed, or these illnesses may be
      misdiagnosed. A systematic and detailed initial history from the patient and a
      reliable family member is essential to making the correct diagnosis. The Mood
      Disorder Questionnaire, a validated screening instrument for bipolar disorder,
      may help primary care physicians make an appropriate diagnosis. Long-term
      management of patients with bipolar disorder should involve close liaison with a
      psychiatrist.

PMID- 15486601
TI  - Passages.

PMID- 15486600
TI  - Using Psychostimulants to Treat Depression in the Medically Ill.
AB  - LESSONS LEARNED AT THE INTERFACE OF MEDICINE AND PSYCHIATRY: The Psychiatric
      Consultation Service at Massachusetts General Hospital (MGH) sees medical and
      surgical inpatients with comorbid psychiatric symptoms and conditions. Such
      consultations require the integration of medical and psychiatric knowledge.
      During their thrice-weekly rounds, Dr. Huffman and Dr. Stern discuss the
      diagnosis and management of conditions confronted. These discussions have given
      rise to rounds reports that will prove useful for clinicians practicing at the
      interface of medicine and psychiatry.

PMID- 15486602
TI  - Terms of Endearment.

PMID- 15486603
TI  - Treatment of Acute Mania With Aripiprazole in an Older Adult With Noted
      Improvement in Coexisting Parkinson's Disease.

PMID- 15486604
TI  - Ethical conduct of journal editors.

PMID- 15486605
TI  - Glyceraldehyde-3-phosphate dehydrogenase as a target for small-molecule disease
      modifying therapies in human neurodegenerative disorders.
AB  - Recent articles have highlighted numerous additional functions of glyceraldehyde
      3-phosphate dehydrogenase (GAPDH) that are independent of its well-documented
      glycolytic function. One of the most intriguing of these functions is as an
      initiator of programmed cell death cascades. This activity involves a nuclear
      appearance of GAPDH, a considerable proportion of which requires synthesis of new
      GAPDH protein and has characteristics suggesting the involvement of a novel
      isozyme. The relevance of such findings to human neurodegenerative conditions is
      emphasized by the increased nuclear GAPDH observed in postmortem samples from
      patients with Parkinson's disease, Alzheimer's disease, Huntington's disease and
      glaucoma, among others. A number of small-molecule compounds have now been
      identified that show anti-apoptotic activity because of their ability to interact
      with GAPDH and prevent its nuclear accumulation. These compounds, one of which is
      currently being tested in late-stage Phase II clinical trials as a disease
      modifying therapy for Parkinson's disease, have potential utility in the
      treatment of human neurodegenerative conditions.

PMID- 15486607
TI  - Peripheral thyroid hormones and response to selective serotonin reuptake
      inhibitors.
AB  - OBJECTIVE: To examine the relation between baseline measurements of thyroid
      function and response to selective serotonin reuptake inhibitors (SSRIs) and to
      consider the effect of these antidepressants on thyroid hormone levels. METHODS:
      Nineteen subjects with major depression, but without a history of thyroid
      treatment or lithium treatment, were treated openly with either sertraline or
      fluoxetine in a university- affiliated tertiary care hospital. Hamilton
      Depression Rating Scale (Ham-D) scores were measured before and after treatment.
      Clinical Global Impressions (CGI) scores were measured at study end. Thyroid
      data, consisting of values for thyroid-stimulating hormone (TSH),
      triiodothyronine (T(3), measured by radioimmunoassay [RIA]), thyroxine (T(4),
      measured by RIA) and free T(4), were collected before and after treatment.
      Complete thyroid data were available for 17 subjects. Data were collected during
      1997-1999. RESULTS: Baseline TSH correlated strongly with response to treatment
      as measured by change in Ham-D scores (r = 0.64, p = 0.003). Low TSH values
      correlated with greater improvement in depressive symptoms. Thyroid hormone
      levels decreased with treatment, but these decreases did not correlate with
      clinical improvement. CONCLUSION: Baseline thyroid function, as measured by serum
      TSH, may predict a patient's response to antidepressant treatment with SSRIs.
      Optimal thyroid function, beyond simply being within the normal laboratory
      values, may be necessary for an optimal response to antidepressants.

PMID- 15486610
TI  - The health of the public.

PMID- 15486611
TI  - Mary Angharad Guy.

PMID- 15486612
TI  - The healing Buddha.

PMID- 15486613
TI  - Sir William Newbigging (1772-1852) and Patrick Newbigging (1813-1864)-father and
      son presidents of the Royal College of Surgeons of Edinburgh.
AB  - Sir William Newbigging was a surgeon to the Edinburgh Royal Infirmary from 1802.
      While a dextrous operator, he was regarded principally as an excellent general
      practitioner. He was President of the Royal College of Surgeons of Edinburgh 1814
      16 and was knighted by Queen Victoria in 1838. He had five sons, four of whom
      followed him into the medical profession. Four of his sons died young-only
      Patrick outlived him. When Patrick returned from a Continental tour in 1842 he
      joined his father's general practice and when Sir William died in 1852 he took it
      over. From 1861 to 1863 he was also President of the Royal College of Surgeons of
      Edinburgh. His last few years were plagued by ill health and he died in 1864,
      shortly after his fiftieth birthday.

PMID- 15486606
TI  - Mother to infant or infant to mother? Reciprocal regulation of responsiveness to
      stress in rodents and the implications for humans.
AB  - Optimal early development in most species is dependent upon a stable relationship
      between the mother and her infant. The research described here focuses on the
      reciprocal nature of this dyad in rodents and humans, with respect to the
      regulation of responsiveness to stress in both mother and offspring. Dietary
      influences are critical not only to regulate infant growth but also to modulate
      the response of the neuroendocrine system to stress and, possibly, to influence
      some aspects of brain development. In particular, we discuss the role of leptin,
      a protein produced in the adipose tissue and present in maternal milk, that
      reduces responses to stress in the infant. We suggest that leptin acts on both
      central (hypothalamus and hippocampus) and peripheral (pituitary, adrenal gland)
      targets in the infant to reduce exposure to glucocorticoids and enhance
      hippocampal development during a sensitive period of brain development. There is
      also evidence to support the reverse regulatory influence, in which maternal
      state is profoundly affected by stimulation from the young. During the period of
      lactation, mothers exhibit lower neuroendocrine and behavioural responses to
      several types of stressors, except possibly those representing a threat to the
      infant. This ability to "filter" relevant from irrelevant stimuli while caring
      for their young might be viewed as adaptive for the mother-infant dyad, and the
      inability to filter adequately stressful stimuli could at least in part be
      associated with the development of postpartum depression.

PMID- 15486614
TI  - Sir James Mouat, VC KCB FRCS (1815-1899): winner of the first medical Victoria
      Cross.
AB  - Sir James Mouat was the first of 36 doctors to win the Victoria Cross. Born in
      Kent in 1815, he was educated at University College London before joining the
      army. After service in India and Ireland he joined the 6th Dragoon Guards as
      regimental surgeon and served with them throughout the Crimean War. He won his VC
      at the Battle of Balaclava. After the Crimean War he was appointed principal
      medical officer to the British troops in the New Zealand Wars. After serving in
      New Zealand he returned to England and became Inspector General of Hospitals.
      Surgeon General Mouat retired on 28 April 1876. He was appointed an honorary
      surgeon to the Queen in 1888, and a Knight Commander of the Order of the Bath in
      1894. He died of a stroke on 4 January 1899 at the age of 83.

PMID- 15486615
TI  - Joseph Clover, FRCS (1825-1882).

PMID- 15486616
TI  - Thomas Morison Legge (1863-1932): the first medical factory inspector.
AB  - After a brief career in public health, Thomas Morison Legge was appointed to
      become the first medical factory inspector, in 1898, and remained in post until
      his resignation in 1927. During his tenure in office he became the leading
      authority on lead poisoning and anthrax; he resigned when the government refused
      to ratify the White Lead Convention. Subsequently he became the first medical
      adviser to the Trades Union Congress.

PMID- 15486617
TI  - Norman Bethune (1890-1939).

PMID- 15486618
TI  - The first woman doctor from Aberystwyth: Mary Angharad Guy (nee Hughes) (1905
      1994).
AB  - Mary Angharad Guy was born one of three daughters of an affluent seafaring
      family. After preclinical education in Cardiff she proceeded to Charing Cross
      Hospital, London, for her clinical studies and on qualification worked with
      eminent men. She married John Guy, who became county medical officer for
      Westmorland, and they had three children. She gave up her career after marriage
      and it was another 15 years before she returned to work, to undertake school and
      baby clinics. She was a woman of outstanding promise and gifted artistically, but
      she was caught in a social trap between the wars, when women were expected to
      give up professional careers on marriage.

PMID- 15486619
TI  - William Charles Wells (1757-1817).

PMID- 15486620
TI  - Carl Liebermeister (1833-1901): a pioneer of the investigation and treatment of
      fever and the developer of a statistical test.
AB  - In the second half of the nineteenth century, when the typical course of various
      febrile clinical phenomena was found to be specific to particular infectious
      diseases, Carl Liebermeister successfully pioneered the investigation of the
      patho physiology of fever and the regulation of body temperature. He applied
      biophysical and pharmacological antipyresis, especially for the treatment of
      typhoid fever, and developed new statistical tools for the evaluation of
      therapeutic results.

PMID- 15486621
TI  - A portrait of Fielding H Garrison (1870-1935): America's pioneering medical
      historian.
AB  - Fielding Hudson Garrison once remarked that because his birthday fell on 5
      November, Guy Fawkes Day, he was "fated to suffer from in-ward hell-fire and
      brimstone all [his] life". Though said in jest, Garrison was a vulnerable,
      melancholic and self-confessed lonely man who found solace in the papers,
      periodicals and books of the Army Medical Library-today's National Library of
      Medicine. Over the course of approximately 25 years, and often while working in
      his spare time, Garrison went from a clerk in the world's largest medical library
      to America's pioneering and, arguably, most prolific medical historian, past or
      present.

PMID- 15486622
TI  - "It is wisest here, as always, to maintain a balance": the medical dissertations
      of Friedrich Schiller.
AB  - Johann Christoph Friedrich Schiller (1759-1805) is remembered today for his
      contributions to literature and aesthetic theory-it is less well known that his
      first career was in medicine (an army appointment). Scholars have generally held
      that his primary interest lay in psychology and the psychological aspects of
      medicine, and that his commitment to other aspects of medicine was perfunctory at
      best. The present paper argues that a study of Schiller's three medical
      dissertations-two on psychological aspects of medicine and one on fevers-reveals
      his attempt "to maintain a balance" between the mind and the body in his approach
      to medicine.

PMID- 15486623
TI  - The healing Buddha.
AB  - The iconography of the healing Buddha embraces two healing traditions, symbolized
      by the healing stone lapis lazuli from Central Asia and by the myrobalan fruit
      from the ayurvedic medicine of ancient India. The first mention of the healing
      Buddha is in Buddhist texts of the first century BC, and the earliest extant
      icons date from the fourth century AD. This suggests the cult of the healing
      Buddha was a relatively late development in the history of Buddhism. Worshippers
      sought his help in alleviating spiritual, mental and physical suffering, as well
      as for medical cures. In China followers believed he was also a cosmic Buddha, to
      whom one appealed for longevity and protection from disasters. This form of faith
      based healing remains vibrant in China, Japan and Tibet to this day.

PMID- 15486624
TI  - Wellcome Bibliography for the History of Medicine.

PMID- 15486625
TI  - Biography as history.

PMID- 15486627
TI  - Proceedings of the 9th International Symposium on Schistosomiasis. 2-5 November
      2003, Salvador, Brazil.

PMID- 15486628
TI  - The role of the scientific research in the control of schistosomiasis in endemic
      areas.
AB  - The way the researches established the lines of direction for considering fight
      against schistosomiasis on the double aspect of transmission and morbidity
      control is outstanding. Chemotherapy in the morbidity control is emphasized. The
      research priorities for schistosomiasis control are mentioned.

PMID- 15486629
TI  - Epidemiological and control aspects of schistosomiasis in Brazilian endemic
      areas.
AB  - The present work analyzes the epidemiology of schistosomiasis in Brazil, its
      expansion, the attempts to control the disease, and the overall difficulties. The
      authors present the distribution of schistosomiasis intermediary hosts in Brazil,
      the migration routes of the human population, and disease distribution in highly
      and lowly endemic areas and isolated foci. They also analyze the controlling
      programs developed from 1977 to 2002, indicating the prevalence evolution and the
      reduction of disease morbi-mortality. In addition, the authors also evaluate
      controlling methods and conclude that: (a) no isolated method is able to control
      schistosomiasis, and every controlling program should consider the need of a
      multidisciplinary application of existing methods; (b) in long term, basic
      sanitation, potable water supply, as well as sanitary education, and community
      effective participation are important for infection control; (c) in short term,
      specific treatment at endemic areas, associated with control of intermediary
      hosts at epidemiologically important foci, are extremely relevant for controlling
      disease morbidity, although not enough for interrupting infection transmission.

PMID- 15486630
TI  - Cytokine profile associated with human chronic schistosomiasis mansoni.
AB  - This study objective was to evaluate the cytokines associated with early events
      of hepatic fibrosis in schistosomiasis mansoni. Hepatic fibrosis was classified
      by ultrasonography in 94 patients. Immunological evaluation was performed by
      measurement of secreted cytokines (interleukin IL-5, IL-10, IL-13, interferon
      gamma, tumor necrosis factor-alpha and transforming growth factors-beta) in
      peripherl blood mononuclear cells stimulated by Schistosoma mansoni antigens.
      Significantly, higher levels of IL-5, IL-10 and IL-13 were found in supernatants
      of SEA-stimulated PBMC from subjects with degree III hepatic fibrosis as compared
      to patients with degree I or II fibrosis, Significant increases in IL-5 and IL-13
      levels were also observed in some of the subjects who remained untreated for one
      year following initial assessment and developed more serious fibrosis during this
      period. The data suggests a role for type 2 cytokines in early stages of hepatic
      fibrosis in human schistosomiasis mansoni.

PMID- 15486631
TI  - Schistosoma mansoni infection modulates the immune response against allergic and
      auto-immune diseases.
AB  - Chronic Schistosoma mansoni infection leads to a type 2-immune response with
      increased production of interleukin (IL-10). Evidence indicates chronic exposure
      to S. mansoni down regulates the type 1 immune response and prevents the onset of
      Th1-mediated diseases such as multiple sclerosis, diabetes mellitus and Crohn's
      disease. Furthermore, our own studies have revealed that chronic exposure to S.
      mansoni also down regulates atopic disease, Th2-mediated diseases. Our studies
      show an inverse association between the skin prick test reactivity and infection
      with S. mansoni and show the severity of asthma is reduced in subjects living in
      an endemic area of S. mansoni. Moreover, we hypothesize the mechanisms involved
      in the modulation of inflammatory response in atopic individuals, is likely
      dependent on IL-10 production, an anti-inflammatory cytokine elevated during
      helminth infections. Patients with asthma and helminth infections produced less
      IL-5 than patients with asthma without helminth infections, and this down
      regulation could, in part, be mediated by IL-10. In conclusion, helminthic
      infections, through induction of regulatory mechanisms, such as IL-10 production,
      are able to modulate the inflammatory immune response involved in the pathology
      of auto-immune and allergic disease.

PMID- 15486632
TI  - Schistosomiasis protects against multiple sclerosis.
AB  - The incidences of schistosomiasis and multiple sclerosis (MS) are mutually
      exclusive worldwide suggesting that schistosomiasis may offer protection against
      the induction of the immune-mediated disease, MS. Recent studies using the mouse
      model of MS, experimental autoimmune encephalomyelitis, support a direct
      suppression of the onset of MS by chronic Schistosoma mansoni infection. Self
      reactive Th1 but not Th2 responses develop in infected mice immunized with myelin
      oligodendrocyte glycoprotein albeit at reduced levels indicating that the
      induction of auto-reactive T cells is not abolished nor phenotypically altered.
      CNS infiltration by inflammatory cells, particularly macrophages, is
      significantly reduced in S. mansoni-infected, immunized mice compared to
      uninfected, immunized mice. Because activated macrophages are crucial to the
      induction of clinical disease, these findings support the hypothesis that
      differences in macrophage activation may contribute to the reduced incidence and
      delayed progression of experimental autoimmune encephalomyelitis during
      schistosomiasis.

PMID- 15486633
TI  - Vaccination with antioxidant enzymes confers protective immunity against
      challenge infection with Schistosoma mansoni.
AB  - Schistosoma mansoni, an intravascular parasite, lives in a hostile environment in
      close contact with host humoral and cellular cytotoxic factors. To establish
      itself in the host, the parasite has evolved a number of immune evasion
      mechanisms, such as antioxidant enzymes. Our laboratory has demonstrated that the
      expression of antioxidant enzymes is developmentally regulated, with the highest
      levels present in the adult worm, the stage least susceptible to immune
      elimination, and the lowest levels in the larval stages, the most susceptible to
      immune elimination. Vaccination of mice with naked DNA constructs containing
      Cu/Zn cytosolic superoxide dismutase (CT-SOD), signal-peptide containing SOD or
      glutathione peroxidase (GPX) showed significant levels of protection compared to
      a control group. We have further shown that vaccination with SmCT-SOD but not
      SmGPX results in elimination of adult worms. Anti-oxidant enzyme vaccine
      candidates offer an advance over existing vaccine strategies that all seem to
      target the larval developmental stages in that they target adult worms and thus
      may have therapeutic as well as prophylactic value. To eliminate the potential
      for cross-reactivity of SmCT-SOD with human superoxide dismutase, we identified
      parasite-specific epitope-containing peptides. Our results serve as a basis for
      developing a subunit vaccine against schistosomiasis.

PMID- 15486634
TI  - From genomes to vaccines via the proteome.
AB  - An effective vaccine against schistosomiasis mansoni would be a valuable control
      tool and the high levels of protection elicited in rodents and primates by
      radiation-attenuated cercariae provide proof of principle. A major obstacle to
      vaccine development is the difficulty of identifying the antigens that mediate
      protection, not least because of the size of the genome at 280Mb DNA encoding
      14,000 to 20,000 genes. The technologies collectively called proteomics,
      including 2D electrophoresis, liquid chromatography and mass spectrometry, now
      permit any protein to be identified provided there is extensive DNA data, and
      preferably a genome sequence. Applied to soluble (cytosolic) proteins from
      schistosomes, proteomics reveals the great similarity in composition between life
      cycle stages, with several WHO vaccine candidates amongst the most abundant
      constituents. The proteomic approach has been successfully applied to identify
      the secretions used by cercaria to penetrate host skin, the gut secretions of
      adult worms and the proteins exposed on the tegument surface. Soluble proteins
      can also be separated by 2D electrophoresis before western blotting to identify
      the full range of antigenic targets present in a parasite preparation. The next
      step is to discover which target proteins represent the weak points in the worm's
      defences.

PMID- 15486635
TI  - Schistosomal hepatopathy.
AB  - Gross anatomical features and a complex set of vascular changes characterize
      schistosomal hepatopathy as a peculiar form of chronic liver disease, clinically
      known as "hepatosplenic schistosomiasis". It differs from hepatic cirrhosis,
      although clinical and pathological aspects may sometimes induce confusion between
      these two conditions. Intrahepatic portal vein obstruction and compensatory
      arterial hypertrophy render the hepatic parenchyma vulnerable to ischemic insult.
      This may lead to focal necrosis, which may give place to focal post-necrotic
      scars. These events are of paramount importance for the clinico-pathological
      evolution of schistosomal hepatopathy. Although portal fibrosis due to
      schistosomiasis sometimes reveals numerous myofibroblasts, it does not mean that
      such fibrosis belongs to a peculiar type. Damage to the muscular walls of the
      portal vein may be followed by dissociation of smooth muscle cells and their
      transition toward myofibroblasts, which appear only as transient cells in
      schistosomal portal fibrosis. Studies made with plastic vascular casts,
      especially those with the murine model of "pipestem" fibrosis have helped to
      reveal the mechanisms involved in systematized portal fibrosis formation.
      However, the factors involved in the pathogenesis of hepatosplenic disease remain
      poorly understood. A process of chronic hepatitis is a common accompaniment of
      portal fibrosis in schistosomiasis. Most of the times it is caused by concomitant
      viral infection. However, no special interaction seems to exist between
      schistosomal hepatopathy and viral hepatitis.

PMID- 15486636
TI  - Involvement of central nervous system in the schistosomiasis.
AB  - The involvement of the central nervous system (CNS) by schistosomes may or may
      not determine clinical manifestations. When symptomatic, neuroschistosomiasis
      (NS) is one of the most severe presentations of schistosomal infection.
      Considering the symptomatic form, cerebral involvement is almost always due to
      Schistosoma japonicum and the spinal cord disease, caused by S. mansoni or S.
      haematobium. Available evidence suggests that NS depends basically on the
      presence of parasite eggs in the nervous tissue and on the host immune response.
      The patients with cerebral NS usually have the clinical manifestations of
      increased intracranial pressure associated with focal neurological signs; and
      those with schistosomal myeloradiculopathy (SMR) present rapidly progressing
      symptoms of myelitis involving the lower cord, usually in association with the
      involvement of the cauda esquina roots. The diagnosis of cerebral NS is
      established by biopsy of the nervous tissue and SMR is usually diagnosed
      according to a clinical criterion. Antischistosomal drugs, corticosteroids and
      surgery are the resources available for treating NS. The outcome is variable and
      is better in cerebral disease.

PMID- 15486637
TI  - Identification of immunodominant epitopes of Schistosoma mansoni vaccine
      candidate antigens using human T cells.
AB  - Paramyosin and Sm14 are two of the six antigens selected by the World Health
      Organization as candidates to compose a subunit vaccine against schistosomiasis.
      Both antigens are recognized by individuals naturally resistant to Schistosoma
      mansoni infection and induced protective immunity in the murine model. Three Sm14
      epitopes and eleven paramyosin epitopes were selected by their ability to bind to
      different HLA-DR molecules using the TEPITOPE computer program, and these
      peptides were synthetically produced. The cellular recognition of Sm14 and
      paramyosin epitopes by peripheral blood mononuclear cells of individuals living
      in endemic area for schistosomiasis was tested by T cell proliferation assay.
      Among all Sm14 and paramyosin epitopes studied, Sm14-3 was preferentially
      recognized by individuals naturally resistant to S. mansoni infection while Para
      5 was preferentially recognized by individuals resistant to reinfection. These
      two peptides represent promising antigens to be used in an experimental vaccine
      against schistosomiasis, since their preferential recognition by resistant
      individuals suggest their involvement in the induction of protective immunity.

PMID- 15486638
TI  - Hypertensive portal colopathy in schistosomiasis mansoni--proposal for a
      classification.
AB  - Portal hypertension is a frequent complication of chronic liver disease, detected
      not only in schistosomiasis, but also in cirrhosis of any etiology. Vascular
      alterations in the colonic mucosa are a potential source for acute or chronic
      bleeding and have been observed in patients with portal hypertension. The purpose
      of this prospective study was to describe and propose a classification for the
      vascular alterations of portal hypertension in the colonic mucosa among patients
      with hepatosplenic schistosomiasis mansoni. One or more alterations of portal
      colopathy were observed in all patients and they were classified according to
      their intensity, obeying the classification proposed by the authors. Portal
      colopathy is an important finding in hepatosplenic schistosomiasis and might be
      the cause of lower gastrointestinal bleeding in patients with severe portal
      hypertension.

PMID- 15486639
TI  - The initial epidemiological studies in the low endemicity schistosomiasis area in
      Esteio, Rio Grande do Sul, the southernmost Brazilian state, 1997 to 2000.
AB  - Nor Biomphalaria glabrata neither Schistosoma mansoni were reported from Rio
      Grande do Sul, the southernmost Brazilian state before 1997. Their detection next
      to the Sinos River, Esteio, confirmed predictions of schistosomiasis expansion to
      the south. Parasitological examinations both in snails and fecal samples from the
      human population were performed from 1997 to 2000. The last 3 out of 5 surveys
      were performed after a preliminar serological screening procedure in a risk group
      identified at a population census. A total of 11 infected individuals were found
      infected and snails from 2 different sites were positive for S. mansoni. Samples
      from these 2 and other sites were identified as B. glabrata. Egg counts in feces
      were below 1 per gram in 6 out of 11 patients. Some socio-cultural perceptions of
      water contact activities next to the Sinos River may cause difficulties to
      control efforts, but they also may be partially acting against a very rapid
      increase in transmission intensity. The southernmost schistomiasis mansoni foci
      in Americas rise the alert for its ongoing expansion.

PMID- 15486640
TI  - Spatial distribution of schistosomiasis foci on Itamaraca Island, Pernambuco,
      Brazil.
AB  - Acute cases of schistosomiasis have been found on the coastal area of Pernambuco,
      Brazil, due to environmental disturbances and disorderly occupation of the urban
      areas. This study identifies and spatially marks the main foci of the snail host
      species, Biomphalaria glabrata on Itamaraca Island. The chaotic occupation of the
      beach resorts has favoured the emergence of transmission foci, thus exposing
      residents and tourists to the risk of infection. A database covering five years
      of epidemiological investigation on snails infected by Schistosoma mansoni in the
      island was produced with information from the geographic positioning of the foci,
      number of snails collected, number of snails tested positive, and their infection
      rate. The spatial position of the foci were recorded through the Global
      Positioning System (GPS), and the geographical coordinates were imported by
      AutoCad. The software packages ArcView and Spring were used for data processing
      and spatial analysis. AutoCad 2000 was used to plot the pairs of coordinates
      obtained from GPS. Between 1998 and 2002 5009 snails, of which 12.2% were
      positive for S. mansoni, were collected in Forte Beach. A total of 27 foci and
      areas of environmental risk were identified and spatially analyzed allowing the
      identification of the areas exposed to varying degrees of risk.

PMID- 15486641
TI  - Malnutrition and hepatic fibrosis in murine schistosomiasis.
AB  - In this paper, four different approaches attempting to reproduce the schistosomal
      liver fibrosis in undernourished mice are reported: shifting from a deficient to
      a balanced diet and vice-versa, repeated infections, influence of the genetic
      background, and immunological response. Infections were performed with 30
      cercariae of Schistosoma mansoni and lasted at least four months. Undernourished
      mice were unable to reproduce the picture of "pipestem" fibrosis, except the C57
      BL/10 inbred strain, four out of 21 mice developing the liver lesion. A link of
      this histological finding to the type of parasite strain can not be discarded at
      the moment. Repeated infections increased collagen deposition mainly in well
      nourished animals (seven out of 16 Swiss mice developed "pipestem"-like
      fibrosis). In undernourished infected Swiss mice the serum levels of soluble egg
      antigen specific antibodies IgG1, IgG2a, IgG2b, and IgG3 were two to four times
      lower than those detected for well nourished controls. The decreased humoral
      immune response coupled to the morphological, morphometric, and biochemical
      results reinforce the influence of the host nutritional status on the connective
      tissue changes of hepatic schistosomiasis.

PMID- 15486642
TI  - Interactions between schistosomiasis and human immunodeficiency virus in Western
      Kenya.
AB  - For the past ten years, we have been exploring the relationship between
      schistosomiasis and human immunodeficiency virus (HIV-1) and how coinfection with
      both agents may affect the pathology and progression of each infection. To date,
      given the systems we have examined, the effects of HIV-1 on schistosomiasis have
      been more profound than the effects of schistosomiasis on HIV-1 progression.
      Additional key questions with important public health implications remain
      unanswered, but hopefully not unanswerable.

PMID- 15486643
TI  - Evaluation of tests based on the antibody response to keyhole limpet haemocyanin
      and soluble egg antigen to differentiate acute and chronic human schistosomiasis
      mansoni.
AB  - Specific IgG and IgM responses to soluble egg antigen (SEA) and keyhole limpet
      haemocyanin (KLH) were measured by ELISA in patients with acute and chronic
      schistosomiasis. The tests based upon IgM and IgG antibodies responses to KLH
      presented the best diagnostic discrimination, and can be used in conjunction with
      clinical and epidemiological data to the differential diagnosis of acute
      schistosomiasis.

PMID- 15486644
TI  - Freshwater snails and schistosomiasis mansoni in the state of Rio de Janeiro,
      Brazil: V -- Norte Fluminense Mesoregion.
AB  - In this paper, the fifth of a series dealing with the survey of freshwater
      gastropods of the state of Rio de Janeiro, the results of collections carried out
      in the Norte Fluminense Mesoregion from 2002 to 2003 are presented and revealed
      the occurrence of 19 species: Antillorbis nordestensis; Burnupia sp.;
      Biomphalaria tenagophila; Drepanotrema anatinum; Drepanotrema cimex; Drepanotrema
      depressissimum; Drepanotrema lucidum; Ferrissia sp.; Gundlachia ticaga;
      Gundlachia sp.; Heleobia sp.; Hebetancylus moricandi; Idiopyrgus sp.; Lymnaea
      columella; Melanoides tuberculatus; Physa acuta; Physa marmorata; Pomacea
      sordida, and Pomacea sp. Concerning the snail hosts of Schistosoma mansoni only
      B. tenagophila was found, in contrast with other previuosly studied
      mesoregions.No specimens were found harbouring larval forms of S. mansoni
      although different kinds of cercariae had been observed. An account about the
      current schistosomiasis transmission sites in this Mesoregion is presented as
      well.

PMID- 15486645
TI  - Rural tourism as risk factor for the transmission of schistosomiasis in Minas
      Gerais, Brazil.
AB  - Recently, the booming rural tourism in endemic areas of the state of Minas Gerais
      was identified as a contributing factor in the dissemination of the infection
      with Schistosoma mansoni. This article presents data from six holiday resorts in
      a rural district approximately 100 km distant from Belo Horizonte, MG, Brazil,
      where a possibly new and until now unperceived way of transmission was observed.
      The infection takes place in swimming pools and little ponds, which are offered
      to tourists and the local population for fishing and leisure activities. The
      health authorities of the district reported cases of schistosomiasis among the
      local population after visiting these sites. As individuals of the non-immune
      middle class parts of the society of big urban centers also frequent these
      resorts, infection of these persons cannot be excluded. A malacological survey
      revealed the presence of molluscs of the species Biomphalaria glabrata and
      Biomphalaria straminea at the resorts. The snails (B. glabrata) of one resort
      tested positive for S. mansoni. In order to resolve this complex problem a
      multidisciplinary approach including health education, sanitation measures,
      assistance to the local health services, and evolvement of the local political
      authorities, the local community, the tourism association, and the owners of the
      leisure resorts is necessary. This evidence emphasizes the urgent need for a
      participative strategic plan to develop the local tourism in an organized and
      well-administered way. Only so this important source of income for the region can
      be ensured on the long term without disseminating the disease and putting the
      health of the visitors at risk.

PMID- 15486646
TI  - Biomphalaria tenagophila/Schistosoma mansoni interaction: premises for a new
      approach to biological control of schistosomiasis.
AB  - Biomphalaria tenagophila is very important for schistosomiasis transmission in
      Brazil. However its mechanisms of interaction with Schistosoma mansoni are still
      scantly studied. Since this snail displays strains highly susceptible or
      completely resistant to the parasite infection, the knowledge of that would be a
      useful tool to understand the mechanism of snail resistance. Particularly, the
      Taim strain consistently shows absolute resistance against the trematode, and
      this resistance is a dominant character. A multidisciplinary research group was
      created aiming at studying B. tenagophila/S. mansoni interaction. The possibility
      for applying the knowledge acquired to obtain a biological model for the control
      of S. mansoni transmission in endemic areas is discussed.

PMID- 15486647
TI  - A Pedagogical approach of schistosomiasis -- an experience in health education in
      Minas Gerais, Brazil.
AB  - The experience described here is part of an extensive program that aims to
      stimulate schools to develop health integrated projects from theme generators,
      i.e., themes that have a meaning for the community. It was developed in
      Jaboticatubas, a town in the metropolitan region of Belo Horizonte, capital of
      the state of Minas Gerais, Brazil, and the focus was schistosomiasis. The
      selection was based on the expressive and historical prevalence of this disease
      in the county, which has been known as the "capital of schistosomiasis", in a
      national press release since the 1960's. Schistosomiasis is also a theme pointed
      out by teachers as requiring more information and methodologies to work with
      their students, most of them living in areas of high risk of transmission. In
      addition, during the last years, this disease has been transmitted silently
      through an increasing rural tourism in that region, requiring integrated and
      effective control actions. The developed strategy included four schools, whose
      teachers, students, and families took part in the process. It emphasizes in a
      critical pedagogy approach, which focuses on health issues as themes that may
      mobilize the school community and awake the population to a work which integrates
      environment, health, and citizenship. The results demonstrate that teachers and
      students not only acquired new knowledge and methodological skills, but also
      gained confidence in their ability to improve their health conditions. Thus, the
      project promotes a critical education that can result a more permanent effect on
      the control of schistosomiasis as well as other benefits for the schools and for
      the population.

PMID- 15486648
TI  - Clinical and immunological consequences of human T cell leukemia virus type-I and
      Schistosoma mansoni co-infection.
AB  - Human T cell leukemia virus type-I (HTLV-I) infection is associated with
      spontaneous T cell activation and uncontrolled lymphocyte proliferation. An
      exacerbated type-1 immune response with production of pro-inflammatory cytokines
      (interferon-gamma and tumor necrosis factor-alpha) is significantly higher in
      patients with myelopathy associated to HTLV-I than in HTLV-I asymptomatic
      carriers. In contrast with HTLV-I, a chronic Schistosoma mansoni infection is
      associated with a type-2 immune response with high levels of interleukin (IL-4,
      IL-5, and IL-10) and low levels of IFN-gamma. In this study, clinical and
      immunological consequences of the HTLV-I and S. mansoni infection were evaluated.
      The immune response in patients with schistosomiasis co-infected with HTLV-I
      showed low levels of IL-5 (p < 0.05) in peripheral blood mononuclear cells
      cultures stimulated with S. mansoni antigen (SWAP) and decreased SWAP-specific
      IgE levels when compared with patients with only schistosomiasis (p < 0.05).
      Liver fibrosis was mild in all HTLV-I co-infected patients. Immunological
      response was also compared in individuals who had only HTLV-I infection with
      those who were co-infected with HTLV-I and helminths (S. mansoni and
      Strongyloides stercoralis). In patients HTLV-I positive co-infected with
      helminths the IFN-gamma levels were lower than in individuals who had only HTLV
      I. Moreover, there were fewer cells expressing IFN-gamma and more cells
      expressing IL-10 in individuals co-infected with HTLV-I and helminths. These
      dates indicate that HTLV-I infection decrease type 2-response and IgE synthesis
      and are inversely associated with the development of liver fibrosis. Moreover,
      helminths may protect HTLV-I infected patients to produce large quantities of pro
      inflammatory cytokines such as IFN-gamma.

PMID- 15486649
TI  - Factors associated with schistosomiasis mansoni in a population from the
      municipality of Jaboticatubas, State of Minas Gerais, Brazil.
AB  - Jaboticatubas is a municipality in the metropolitan region of Belo Horizonte
      which has been a target of a wide media release as "the capital of
      schistosomiasis" since the 1960's. In order to give support to a work based on an
      integrated control, we sought to identify the disease determinants at the site. A
      transversal study was carried out aimed at identifying prevalence rates of the
      disease and factors associated with the infection in the district of Sao Jose de
      Almeida, and two close localities, Cipo Velho and Sao Jose da Serra, all of them
      located in the municipality of Jaboticatubas. A parasitological survey was
      performed, applying the Kato-Katz method with two slides per sample in 1186
      schoolchildren which represents 77% of all registered pupils in four public
      schools in 2001. Among these schoolchildren a number of 101 (8.6%) proved
      positive for Schistosoma mansoni eggs in their stool samples. A total of 64
      families, whose schoolchildren had shown to be positive for schistosomiasis, also
      undertook examinations. As negative control, a random sample was collected from
      the 206 families, whose children had proven negative for schistosomiasis. The
      prevalence among 270 families (1304 people) was 12%. To assess those who
      continued to have contact with possibly contaminated water, 1061 (81.4%) people
      of the 270 families were interviewed. A multivariate analysis identified the
      following factors associated with the infection: time of residence in the area
      (short period), garbage disposal (use of deserted areas), gender (male), age
      (from 10 to 29 years), and water contact (daily and weekly). Further analysis of
      these factors revealed a close correlation between water contact and the disease,
      with a positive significant frequency concerning almost all those items.
      Depending on gender and age significant variations of water contact patterns
      associated with leisure and professional activities were found. A malacological
      survey on water collections in the area identified snails of the species
      Biomphalaria straminea and B. glabrata. The latter showed 17 (0.6%) specimens
      positive for S. mansoni. Qualitative studies have complemented such evidences,
      which allowed us to design a reference picture and specific indicators of the
      disease for the local population. Those data provided the essential information
      to continue the development of an already ongoing educative process, as well as
      projects on environmental improvements.

PMID- 15486650
TI  - More evidence against hormone replacement therapy in menopause.

PMID- 15486651
TI  - [The necessary frugality of the elderly].
AB  - The purpose of this article is to reflect on the pertinence and moral legitimacy
      of basing the allocation of public resources for health on the age variable,
      considered from the perspective of the theory of "justice as equity" as
      formulated by John Rawls. After characterizing the problem of public resource
      allocation for health -- confronted with the challenge posed by population aging 
      - and briefly presenting the concept of equity adopted in this study, as well as
      discussing the approach by Norman Daniels and Daniel Callahan to resource
      allocation among different age groups, we conclude that basing resource
      allocation on the age variable may be considered ethically adequate if we
      conceive the individual's life as a limited cycle of existence formed by
      different stages (childhood, adolescence, maturity, old age, and death), during
      which the needs vary, such that the distribution of resources among different age
      groups should be based on an ethics of protection.

PMID- 15486652
TI  - [The necessary frugality in the application of justice principles].

PMID- 15486653
TI  - [Aging and protection].

PMID- 15486654
TI  - [The necessary frugality: models more contemporary].

PMID- 15486655
TI  - [Aging and Resource allocation in health].

PMID- 15486656
TI  - [The necessary frugality of the elderly].

PMID- 15486658
TI  - [Adequacy of prenatal care and birthweight: a systematic review].
AB  - This was a systematic literature review on publications in which prenatal care
      was investigated as a predictive factor for birthweight. The MEDLINE, Cochrane
      Library, and SciELO databases were searched using a combination of the following
      uniterms: "prenatal care", "antenatal care", "quality", "adequacy",
      "birthweight", and "low birthweight". Twenty-five studies were found: seventeen
      had a cross-sectional design, in addition to four cohort studies, three case
      control studies, and one randomized trial. The adequacy indicators related to
      utilization (quantitative measures) and content of prenatal care (process or
      qualitative indicators). Most authors employed quantitative indicators, mainly
      the Kessner Index and the Adequacy of Prenatal Care Utilization Index.
      Qualitative criteria were used in only two studies. Most of the cross-sectional
      studies found a protective effect of prenatal care against low birthweight,
      whereas results of studies with other designs were conflicting. This review's
      findings highlight that the impact of prenatal care on birthweight is not
      unequivocal, mainly due to the effect of self-selection bias. Randomized trials
      are needed to elucidate such a relationship.

PMID- 15486659
TI  - [Audio Computer-Assisted Interview: a new technology in the assessment of
      sexually transmitted diseases, HIV, and drug use].
AB  - Reliable responses are crucial when applying questionnaires on sensitive and
      stigmatized behaviors. This challenge has motivated researchers to develop new
      data collection methods. We conducted a systematic literature review on the
      implementation, effectiveness, reliability, and validity studies of ACASI (Audio
      Computer-Assisted Interview) in the assessment of drug use and sexual behavior.
      We reviewed 24 papers, none of which published by Brazilian researchers, and only
      three of which describing research implemented outside the United States. The
      studies showed that the computerized method is able to reduce psychological
      barriers linked to the collection of sensitive health-related information,
      thereby increasing its reliability. According to the surveys, the ACASI format is
      a fast and valid assessment method for large samples. ACASI generates databanks
      that can be easily processed and analyzed.

PMID- 15486660
TI  - Determinants of growth retardation in Southern Brazil.
AB  - A cross-sectional population-based study of determinants of growth retardation in
      under-five children (3,389) in the city of Porto Alegre, Rio Grande do Sul,
      Brazil estimated odds ratios (OR) for stunting, defined as height-for-age < -2
      zeta-scores of the NCHS standards. Hierarchical modeling based on a framework of
      the process of stunting was used. Stunting prevalence was 6.8%; the main
      determinants were per capita family income < 0.8 times the minimum wage (OR:
      3.95; 95%CI: 2.10-7.42), maternal illiteracy (OR: 17.17; 95%CI: 4.43-66.54),
      living in a wooden or mixed-construction house (OR: 2.33; 95%CI: 1.35-4.01),
      inadequate housing (OR: 2.75; 95%CI: 1.70-4.43), maternal age at the child's
      birth < 20 years (OR: 1.73; 95%CI: 1.11-2.70), being an adopted child (OR: 3.28;
      95%CI: 1.52-7.07), third-born child or greater (OR: 2.04; 95%CI: 1.15-3.62),
      birth interval < 24 months since previous child (OR: 1.69; 95%CI: 1.13-2.53),
      subsequent sibling (OR: 1.91; 95%CI: 1.16-3.13), multiple birth (OR: 2.40; 95%CI:
      1.04-5.50), low birth weight (OR: 3.79; 95%CI: 2.38-6.02), and hospitalization in
      the first year of life (OR: 1,65; 95%CI: 1.01-2.68). The findings can be used by
      primary healthcare services to design specific interventions to prevent stunting.

PMID- 15486661
TI  - Triatomine infestation and vector-borne transmission of Chagas disease in
      northwest and central Parana, Brazil.
AB  - Triatomine infestation, prevalence of T. cruzi antibodies in humans and domestic
      animals, and variables potentially associated with the presence of triatomines in
      a rural domiciliary unit (DU) were investigated in nine municipalities and one
      district of Parana, Brazil, from June 1996 to February 2000. DUs were defined as
      all houses and annexes on a given piece of property. Blood samples from human
      volunteers, dogs, and cats were submitted to indirect immunofluorescence. An
      epidemiological form was completed for each DU. A logistic model was adopted in
      order to identify associations. Seven out of nine municipalities were positive
      for triatomines. T. infestans was not captured, but T. sordida, P. megistus, and
      R. neglectus were. Different variables were considered decisive for the presence
      of triatomines across the municipalities: proximity to residual wooded areas,
      i.e. either scrub forest (capoeira) or islands of residual forest (slightly dense
      vegetation), longer time of residence, existence of inhabited houses, and past DU
      infestation. In order to ensure proper continuation of the recommended Chagas
      disease control program, entomo-epidemiological surveillance measures need to be
      maintained.

PMID- 15486662
TI  - Provision of female sterilization in Ribeirao Preto, Sao Paulo, Brazil.
AB  - Forty percent of Brazilian married women from 15 to 49 years of age have
      undergone surgical sterilization. The 1988 Brazilian Constitution states that all
      scientifically proven contraceptive methods should be available to all citizens,
      but it was only in 1997 that specific family planning legislation was approved.
      This study examines physicians' perceptions and attitudes towards the current
      provision of female sterilization and its legal implications, as well as women's
      experience with obtaining and undergoing sterilization. The study design
      included: (1) an investigation of the hospitals and health professionals and (2)
      a survey of women sterilized in combination with cesarean delivery in 1998. The
      survey showed they had a median of 3 living children, 60.0% had been sterilized
      between 30 and 39 years of age, and 61.0% had paid for the procedure. Many women
      reported previous method failure and adverse effects with hormonal
      contraceptives. Women with less schooling and lower socioeconomic status had more
      children and had begun childbearing and had been sterilized at younger ages than
      women with more schooling and higher socioeconomic status. Inequalities related
      to reproduction were strongly associated with teenage pregnancy and inadequate
      knowledge about contraceptives.

PMID- 15486663
TI  - Women and AIDS: gender relations and condom use with steady partners.
AB  - An educational project on sexuality, STDs, and AIDS was conducted for four years
      with some 500 women. As a result, changes were observed in HIV-related knowledge
      and attitudes, but not in risk behaviors for infection. This fact motivated the
      development of a qualitative study to learn the reasons why women failed to
      incorporate HIV preventive behaviors into their daily lives. Six focus groups
      were conducted with women who had participated in the educational project. The
      analysis was thematic. Women were familiar with HIV transmission routes and
      preventive measures. They admitted not using condoms due to fear of being
      suspected of infidelity and because this might lead to separation of the couple.
      Women reported that relationships with their partners had been difficult because
      of lack of dialogue and that men always had the final word. Although women had
      information about AIDS, they did not use preventive measures in steady
      relationships because they did not wield decision-making power. Gender inequality
      and fidelity were two significant issues related to the increase in AIDS among
      women.

PMID- 15486664
TI  - Weight loss diets advertised in non-scientific publications.
AB  - Weight-loss diets advertised in mainstream non-scientific publications and
      targeting the adult female public were evaluated in relation to total energy
      value, macronutrients, calcium, iron, vitamins A and E, and cholesterol content,
      as well as the presence of information regarding the duration of diets, fluid
      intake, physical activity, and maintenance diets. Two publications were selected,
      considering periodicity, circulation, readership, and years in publication. The
      Virtual Nutri software was used to evaluate the nutrients of 112 diets.
      Micronutrient content was compared to the Dietary Reference Intakes. All diets
      were inadequate in at least one of the evaluated items. Less than 25.0% of the
      diets presented adequate macronutrient distribution. Calcium, iron, and vitamin E
      were also predominantly inadequate (85.7, 97.3, and 91.9%, respectively). Non
      scientific publications should not be allowed to advertise weight-loss diets. In
      addition, their chemical composition is inadequate and they are not accompanied
      by important instructions for such therapy.

PMID- 15486665
TI  - [Multiple causes of death due to non-communicable diseases: a multidimensional
      analysis].
AB  - This study approaches multiple causes of death to analyze the associations
      between causes of death from non-communicable diseases, age, and gender in 3,106
      death certificates issued in 1998, comprising individuals who were 20 years old
      or over and resided in Belo Horizonte, Minas Gerais State, Brazil. The multiple
      cause of death approach, by considering all the diagnoses mentioned in the death
      certificate, highlights conditions that are underestimated by the underlying
      cause approach that has traditionally been used in mortality statistics.
      Association of causes of death was analyzed using the multidimensional data
      analysis method with the multiple correspondence factor analysis technique. The
      results reinforce the usefulness of the multiple causes approach to improve
      information on mortality and demonstrate important associations, such as
      hypertension and cerebrovascular diseases, obesity and diabetes or ischemic heart
      diseases, allowing to plan, prioritize, and reevaluate health actions.

PMID- 15486666
TI  - [Tumor characteristics and five-year survival in breast cancer patients at the
      National Cancer Institute, Rio de Janeiro, Brazil].
AB  - Numerous factors have been studied to establish more secure prognostic criteria
      in breast cancer patients. This study estimates five-year survival rates and
      principal prognostic factors related to tumor characteristics in women with
      invasive breast cancer and submitted to surgery at the National Cancer Institute,
      Rio de Janeiro, Brazil, from May 1995 to July 1996. Study variables were: lymph
      node status, tumor size, aggressiveness grade, and presence of estrogen and
      progesterone receptors. Survival functions were calculated according to the
      Kaplan-Meyer method. The Cox proportional hazards model was used to evaluate
      prognostic factors. Five-year survival was 75% for all women and 64% for those
      with node involvement. Multivariate analyses identified node involvement as the
      strongest predictor of outcome; a positive estrogen receptor test was associated
      with a better prognosis. These findings highlight the need for studies to assess
      new variables to be added to known factors in order to better orient therapy for
      breast cancer.

PMID- 15486667
TI  - [Efficacy of Fipronil in the control of the peridomiciliary cycle of Triatoma
      infestans in an area resistant to Deltamethrin].
AB  - This study tested the efficacy of liquid Fipronil (1.0%) against Triatoma
      infestans, administered by pouring on birds and mammals both in laboratory and
      field conditions. In the laboratory a chicken, dog, and goat were treated with
      Fipronil, after which deltamethrin-resistant stage III T. infestans nymphs were
      fed on them. The control group used same-stage nymphs reared in laboratory.
      During the field phase, Fipronil was used to treat 4 dogs, 1 cat, and 2 broody
      hens. Intradomiciliary infestation was treated using aerothermics. In laboratory,
      nymphal mortality was 100.0% after 7 days and 88.8% after 30 days. In the field,
      there was a 65.4% decrease in the triatomine density rate after 30 days.

PMID- 15486668
TI  - [Management characteristics in charity hospitals in Brazil].
AB  - This paper presents the management characteristics of charity hospitals in
      Brazil, based on data from a national survey developed in 2001. The sample
      accounted for the random inclusion of 66 Brazilian Unified Health System (SUS)
      inpatient care providers with less than 599 beds and all 26 hospitals with at
      least 599 beds. It also included 10 institutions assumed as non-providers of
      services to the SUS. The analyses are descriptive, focusing on the classification
      of the hospitals according to their managerial development level, as well as
      selected issues regarding the utilization of specific managerial technologies,
      human resources, technical services, and services contracting. Distinct
      managerial levels were identified, but it is important to note that 83% of the
      SUS providers with less than 599 beds were classified as having incipient
      management. The authors discuss implications of the findings for inpatient care
      policies, considering the importance of charity hospitals for the Brazilian
      Health System.

PMID- 15486669
TI  - [Reliability and validity of uterine cancer death certificates in the
      municipality of Belem, Para, Brazil].
AB  - Belem, Para State, Brazil, presents high mortality rates for uterine cervical
      cancer, thus justifying an analysis of the reliability and validity of data on
      this underlying cause of death. Death certificates for Belem residents who died
      in 1998-1999 from neoplasms of the uterine cervix, uterine body, or unspecified
      uterine site, or with mention of such a neoplasm on any line in the death
      certificate, were selected, amounting to 188 death certificates (DCs). All DCs
      were submitted to new coding, and reliability analysis was performed by simple
      agreement and Cohen's kappa. The underlying cause of death, established after
      review of medical records and/or histopathological findings, was considered the
      gold standard for analysis of criteria validity, based on the positive predictive
      value. We observed a simple agreement of 94.0% and kappa of 0.87, suggesting high
      reliability of the official system's coding of uterine cancer as the underlying
      cause of death. In the validity analysis, 120 of the 127 deaths originally
      considered as caused by cancer of the uterine cervix and 3 of the 4 coded as
      cancer of the uterine body were confirmed. An 11.2% increase in uterine cervical
      tumors and a reduction of 62.5% in unspecified uterine tumors were observed.

PMID- 15486670
TI  - [Regionalization as a strategy for the definition of homicide-control public
      policies].
AB  - This article analyzes the spatial distribution of homicide rates in Minas Gerais
      State, Brazil, using data from the Ministry of Health Mortality Information
      System (SIM/MS) from 1996 to 2000. Population data used to calculate rates were
      also obtained from the Brazilian Ministry of Health. Minas Gerais has a large
      territory, so the study used a recently developed statistical methodology
      implemented in the SKATER software to generate homogeneous spatial clusters. The
      technique obtained 24 spatial clusters, in which municipalities with similar
      homicide rates were aggregated. Using these results, the authors discuss the
      possible creation of "public security administration areas" that would allow the
      implementation of public policies aimed at controlling and diminishing homicides
      in municipalities with similar characteristics for this type of crime.

PMID- 15486671
TI  - [The Brazilian Ministry of Health's Program for Humanization of Prenatal and
      Childbirth Care: preliminary results].
AB  - This article evaluates the implementation of the Brazilian Ministry of Health's
      Program for Humanization of Prenatal and Childbirth Care using data generated by
      the SISPRENATAL/DATASUS database from the Unified National Health System. From
      its beginning in June 2000 until December 2002, 3,983 municipalities joined the
      Program, and 71% of participating municipalities (3,183) reported their health
      care activities, constituting a database with 720,871 women. Nearly 20% of the
      women had six or more prenatal visits, and approximately half of them had the
      postpartum follow-up visit and required lab tests performed in 2002. In addition,
      41% of the women had been vaccinated against tetanus. The number of HIV antibody
      tests was twice that of syphilis during the two-year period. Only a small
      percentage of women (2% in 2001 and 5% in 2002) received the entire set of
      prenatal and childbirth care services. The low percentages attest to the need for
      permanent evaluation aimed at improving quality of care and guaranteeing both
      high-quality maternal and perinatal results and the inalienable right of women to
      safe care and well-being during pregnancy and delivery.

PMID- 15486672
TI  - [Socio-demographic factors associated with dental services among Brazilian older
      adults: a study based on the National Household Sample Survey].
AB  - The objective of this study was to determine the prevalence of (and social
      demographic factors associated with) the use of dental services. It was based on
      a sample of 28,943 adults > 60 years of age from the Brazilian National Household
      Sample Survey. Socio-demographic characteristics of seniors who had visited a
      dentist in the last year were compared with those of seniors who had visited a
      dentist more than one year previously and those who had never been to the
      dentist. The study showed independent associations between intervals > 1 year in
      visits to the dentist and such variables as age, residence, years of schooling,
      and per capita household income. All these variables, in addition to male gender
      and residence in the rural area, showed independent associations with absence of
      dental visits during the individual's lifetime. The results indicate a low rate
      of use of dental services among elderly Brazilians and that regional and
      socioeconomic differences are important determinants of dental services' use by
      Brazilian seniors.

PMID- 15486673
TI  - [Rural work and pesticide poisoning].
AB  - Pesticide use is intensive in Brazilian agriculture. Population-based studies on
      the characteristics of pesticide use and pesticide poisoning are scarce. This
      study describes the profile of occupational exposure and pesticide poisoning
      incidence. Farm characteristics and pesticide occupational exposure were
      evaluated using a cross-sectional design. Among 1,379 farmers/farm workers,
      annual incidence of pesticide poisoning was 2.2 episodes per 100 exposed. Based
      on Poisson regression, applying pesticide, reentering crop fields after spraying,
      and working with pesticides on more than one farm were the types of exposure that
      presented a positive correlation with pesticide poisoning. The results may be
      useful for planning activities aimed at reducing occupational pesticide poisoning
      among rural workers.

PMID- 15486674
TI  - [Safe sex negotiation on TV: gender discourses among female community health
      workers under the Family Health Program in Porto Alegre, Rio Grande do Sul,
      Brazil].
AB  - This paper analyzes the understanding among female community health workers in
      the Family Health Program in Porto Alegre, Rio Grande do Sul State, Brazil,
      concerning the notion of safe sex negotiation promoted by the Brazilian
      government in AIDS prevention campaigns targeting women. The paper is based on
      empirical data gathered in 2003. The study focused on TV advertisements used in
      campaigns by the Brazilian Ministry of Health from 1994 to 2000. The analytical
      approach was informed by feminist and cultural studies, taken from a post
      structuralist and Foucauldian perspective. The research aimed to produce
      knowledge to support a critical reading of such education for HIV/AIDS
      prevention, especially concerning gender relations. The paper argues that
      knowledge and practices permeating the "safe sex negotiation" discourse
      incorporate, reproduce, and/or transmit hegemonic representations of masculinity
      and femininity and that these representations differentiate and highlight
      hierarchical positions of women in relation to men and/or women in relation to
      other women, producing and/or reinforcing prejudices and inequalities.

PMID- 15486675
TI  - [The bioethics of protection and the state's role: moral problems in unequal
      access to drinking water].
AB  - The aim of this study is to examine unequal access to drinking water as a public
      health problem in terms of normative and analytical tools in the bioethics of
      protection. Therefore, we analyze both the moral implications of unequal
      treatment of primary needs, such as situations of vulnerability and threat to
      population groups, and the public sector's responsibility in supplying safe
      water. In addition, solutions are proposed for the protection of public health
      and the promotion of legitimate personal development projects. The bioethics of
      protection reaffirms the state's role in maintaining the drinking water supply
      and recommends avoiding a policy of privatization of this public good, meanwhile
      justifying public policies to correct situations of social injustice.

PMID- 15486676
TI  - [Community health agents and patients' privacy].
AB  - This is an exploratory study on views of various social players in the Brazilian
      Family Health Program, concerning the right to privacy in the relationship
      between users of the program and community health agents (CHA). The following
      healthcare professionals were interviewed: heads of basic healthcare units,
      physicians, nurses and community health agents, working at health units in the
      city of Sao Paulo, Brazil, in 2002. Healthcare professionals and managers agreed
      that limits should be placed on access by CHAs to certain user information,
      including diagnosis. The study showed that frequent contact between users and
      CHAs results in users' disclosure of their health conditions to CHAs prior to
      consulting other professionals in the healthcare team. This generates the
      following ethical issue: Is there any specific scope of confidentiality between
      the CHA and users over information that should not be disclosed to other team
      members?

PMID- 15486677
TI  - [Dengue epidemics and press coverage].
AB  - The occurrence of successive dengue epidemics in Brazil highlights the importance
      of information dissemination by the media. As a sphere for mediation in
      contemporary societies, the news media produce, expand, and circulate information
      and meanings that affect people's decisions. In order to contribute to the
      discussion, this study analyzes coverage by the main daily newspaper in Belo
      Horizonte, Minas Gerais, Brazil, on dengue epidemics in that State capital from
      1996 to 2000, assessing the priority ascribed to the epidemics as news and the
      various approaches to the disease. Some 446 news stories were selected,
      classified according to the themes approached in the titles and in the body of
      the articles. There was a close relationship between the number of news stories
      and the number of reported dengue cases, with "peaks" in coverage coinciding with
      outbreaks. According to this study, the news priority for epidemics and the
      limited space reserved for prevention highlight the need for epidemiological
      surveillance services to consider strategies to disseminate information through
      the mass media, aimed at fostering more participatory interventions that would
      thus be more efficient in the prevention of epidemics.

PMID- 15486678
TI  - [Humanization of healthcare services and the right to healthcare].
AB  - This article discusses the possibilities and limits of proposals for the
      humanization of healthcare. The theoretical references utilized are the concept
      of "reification" as a causative explanation for the process of man's estrangement
      from his world and the concept of "radical needs" as a possible way of overcoming
      traditionalist humanism to achieve transformative practice. From these notions,
      an understanding of the difficulties and contributions of the movement towards
      humanization is sought, highlighting the interdependence and limits of sectoral
      changes within healthcare in light of society's concepts and general values. The
      article concludes by suggesting that guidelines for humanization/satisfaction, in
      bringing together the critique of society's general questions concerning the
      daily difficulties of healthcare services, may keep the comprehensiveness of the
      right to healthcare open beyond the limits of current social relations, thereby
      favoring a stance that opposes the restrictive trend of minimal public policies
      towards healthcare.

PMID- 15486679
TI  - [Health promotion, social epidemiology, and social capital: associations and
      perspectives for public health].
AB  - The idea of health promotion predates the use of the actual term. However, the
      incorporation of this idea and the practice of health promotion were influenced
      by the Canadian health reform movement, which echoed the voices of many others
      who were concerned with the influence of the physical and social environment on
      health. This provided the basis for the World Health Organization to launch a
      series of conferences beginning with the Alma Ata Conference in 1977 and followed
      by the Ottawa Conference, from which resulted the first international document on
      health promotion, known as the Ottawa Charter. Although health promotion has been
      the subject of a wide range of studies, the concept is still not well understood
      and its explicit practice is limited. Health conferences have been important for
      keeping the notion of equity in health alive, while the gap between the rhetoric
      of these conferences and practice remains to be bridged. However, the rise of
      social epidemiology and the development of the concept of social capital for
      health could bring new insights into traditional epidemiology in order to narrow
      this gap. The purpose of this paper is to elucidate these concepts and to
      describe the roles they play in public health in order to stimulate further
      debate.

PMID- 15486680
TI  - [Female health workers: lifestyle, work, and psychiatric disorders].
AB  - The relationships were studied between daily life, work, and mental disorders in
      female health workers from the Mexican Health Insurance Institute. The study
      sample (n = 170) included female physicians, nurses, laboratory workers, and
      medical assistants. Primary data were obtained through an interview which had
      been previously validated in a population of workers in Mexico. Relationships
      were found between mental disorders and all facets of women's lives. In relation
      to the domestic environment, women with higher rates of mental disorders were
      those who were mothers, had more children, did not have household help, and had
      husbands or partners. Prevalence of mental disorders in relation to paid work was
      associated with the length of the workday, absenteeism, and lack of job content.
      Skills development, job satisfaction, and creativity had a "protective" or
      preventive effect against mental disorders and fatigue. The main risks and
      conditions that functioned as stressors were heat, noise, physical effort,
      awkward positions, and intense, repetitive work.

PMID- 15486681
TI  - [Cognitive traps: the case of omission in the genesis of work-related accidents].
AB  - This article discusses omissions in work-related accidents. The authors present
      James Reason's concepts on task characteristics which can increase the chance of
      operator omission. These ideas were applied to three accidents in which worker
      omission was given as the "cause" and "proof" of victim's guilt. Analysis of
      these accidents as a stepwise sequence of activities shows at least four of
      Reason's omissions characteristics. The expression "cognitive trap" is used to
      describe their simultaneous presence, and these omissions are highlighted as an
      organizational aspect requiring consideration in accident-prevention strategies.

PMID- 15486682
TI  - [Representations of alcoholism in a former alcoholics' association: Alcoholics
      Anonymous].
AB  - This article is designed to review the representations of alcoholism provided by
      members of an association of former alcoholics, namely Alcoholics Anonymous (AA),
      based on partial results from a qualitative survey conducted in the Sapopemba
      group of AA in a neighborhood on the outskirts of the city of Sao Paulo, Brazil.
      The article thus analyzes alcoholism from an emic perspective, i.e., how it is
      conceived and managed by those who acknowledge themselves as being "sick as
      alcoholics", how they explain the sickness, how they experience it, and how they
      endeavor to overcome it. The purpose is to present AA and its treatment strategy
      and to highlight the link made by the association by conceiving of alcoholism as
      a physical, moral, and spiritual illness.

PMID- 15486683
TI  - [HIV patients' understanding of information on antiretroviral therapy].
AB  - To assess the understanding of information related to antiretroviral therapy
      among HIV-infected patients enrolled in public AIDS services (Belo Horizonte,
      Minas Gerais State, Brazil), a cross-sectional analysis was carried out, based on
      interviews with patients after initial provision of antiretroviral drugs. The
      study evaluated the information on antiretroviral therapy provided by healthcare
      professionals and the patients' level of understanding in relation to
      prescription information. This level was classified as insufficient if there was
      disagreement of more than 30.0% between the information reported by the patient
      and the written prescription. Divergence between prescriptions and information
      reported by 358 interviewed patients was observed. The level of understanding
      regarding the prescribed antiretroviral was obtained, and 26.3% of patients
      displayed insufficient understanding. The results show an important proportion of
      patients with misunderstanding of information regarding antiretroviral therapy,
      mainly those with limited schooling and low income. It is necessary to bolster
      strategies to increase quality of recommendations provided to these patients.
      Improving the multidisciplinary team approach to patient care should help reverse
      the observed situation.

PMID- 15486685
TI  - [Changes in undergraduate education in the health professions from the
      perspective of comprehensive training].
AB  - This article discusses the issue of legal, technical, and political legitimacy
      for formulating a public policy aimed at organizing the training of health
      professionals in accordance with the population's health needs, while
      highlighting the competencies of the education and health sectors in this
      construction. Comprehensiveness is viewed as the main thrust for proposing and
      supporting the changes needed in the training of professionals in education and
      health, since it involves an expanded understanding of health, the linkage among
      multi-professional and interdisciplinary knowledge and practices, and
      dialogue/exchange with health system users, aimed at innovation of practices in
      all scenarios of health care and health sector management.

PMID- 15486686
TI  - [Comprehensiveness in practice (or, on the practice of comprehensiveness)].
AB  - This article reflects on the manifestations or signs of comprehensiveness in
      health practice, seeking to facilitate recognition of experiences that are
      advancing in this direction and allowing them to be analyzed subsequently. The
      article is also intended to spawn increasing involvement by actors in practices
      based on comprehensiveness. The point of departure is the principle that what
      characterizes comprehensiveness is an expanded grasp of the needs and ability to
      recognize the adequacy of the health care supply in the specific context where
      the subject meets the health team; in addition, to foster comprehensiveness means
      defending the notion that health actions be attuned to the specific context of
      each encounter.

PMID- 15486687
TI  - [Evaluation of comprehensiveness: ascribing meaning to agreements on goals for
      local health systems].
AB  - As a policy guideline, ideal, or objective, comprehensiveness is a relevant
      attribute in the evaluation of quality of care and health systems. The article
      discusses the meaning of the concept of comprehensiveness in practice in some
      health services and systems, analyzing various methodologies to implement the
      concept. In Brazil, what prevails is an expanded perception emphasizing the
      complete, continuous, and coordinated nature of health care and management. The
      article highlights the importance of combining the evaluation of
      comprehensiveness with measures of access, suggesting the selection of indicators
      pertaining to agreements on goals for local health systems and their monitoring.
      This initiative could enhance the validity of existing evaluation instruments,
      from a communications perspective.

PMID- 15486688
TI  - [Epidemiological characteristics of dengue in the Municipality of Sao Luis,
      Maranhao, Brazil, 1997-2002].
AB  - A total of 12,008 cases of dengue were reported from 1997 to 2002, with peaks in
      1997 (35.8%) and 1998 (45.8%). The disease predominated in the 15-49-year age
      group (72.2%) and during the rainy season (83.3%), showing a positive correlation
      with the amount of rainfall (r = 0.84) and relative humidity (r = 0.76) and a
      negative correlation with temperature (r = -0.78). There was no significant
      difference (chi2 = 2.319; p > 0.05) in the number of cases in males (49%) and
      females (51%). Dengue was detected in all seven health districts: Tirirical
      (27%), Coroadinho (17%), Bequimao (16%), Cohab (14%), Itaqui-Bacanga (11%),
      Centro (8%), and Vila Esperanca (7%). The building infestation rate ranged from
      1.01 to 7.15, and the Breteau index ranged from 1.10 to 8.18. The most frequent
      mosquito breeding sites were metal barrels or similar recipients (80.0%),
      followed by plant vases (4.7%), bottles, cans, and plastics (3.6%), tires (3.3%),
      water tanks (2.7%), and others (5.7%). In the case of Aedes aegypti, 134,631
      positive water deposits were detected, with a predominance of type B (80.0%),
      followed by types C (4.7%), E (3.6%), and A (3.3%).

PMID- 15486690
TI  - Amino acid patterns within short consensus repeats define conserved duplicons
      shared by genes of the RCA complex.
AB  - Complement control proteins (CCPs) contain repeated protein domains, short
      consensus repeats (SCRs), which must be relevant to diverse functions such as
      complement activation, coagulation, viral binding, fetal implantation, and self
      nonself recognition. Although SCRs share some discontinuous and imperfect motifs,
      there are many variable positions and indels making classification in subfamilies
      extremely difficult. Using domain-by-domain phylogenetic analysis, we have found
      that most domains can be classified into only 11 subfamilies, designated a, b, c,
      d, e, f, g, h, i, j, or k and identified by critical residues. Each particular
      CCP is characterized by the order of representatives of the subfamilies. Human
      complement receptor 1 (CR1) has ajefbkd repeated four times and followed by ch.
      The classification crosses CCPs and indicates that a particular CCP is a function
      of the mix of SCRs. The aje set is a feature of several CCPs including human CR1
      and DAF and murine Crry and appears to be associated with the success or failure
      of implantation inter alia. This approach facilitates genomic analysis of
      available sequences and suggests a framework for the evolution of CCPs. Units of
      duplication range from single SCRs, to septamers such as efbkdaj, to extensive
      segments such as MCP-CR1L. Imperfections of duplication with subsequent deletion
      have contributed to diversification.

PMID- 15486691
TI  - Phylogenetic analysis of proteins associated in the four major energy metabolism
      systems: photosynthesis, aerobic respiration, denitrification, and sulfur
      respiration.
AB  - The four electron transfer energy metabolism systems, photosynthesis, aerobic
      respiration, denitrification, and sulfur respiration, are thought to be
      evolutionarily related because of the similarity of electron transfer patterns
      and the existence of some homologous proteins. How these systems have evolved is
      elusive. We therefore conducted a comprehensive homology search using PSI-BLAST,
      and phylogenetic analyses were conducted for the three homologous groups (groups
      1-3) based on multiple alignments of domains defined in the Pfam database. There
      are five electron transfer types important for catalytic reaction in group 1, and
      many proteins bind molybdenum. Deletions of two domains led to loss of the
      function of binding molybdenum and ferredoxin, and these deletions seem to be
      critical for the electron transfer pattern changes in group 1. Two types of
      electron transfer were found in group 2, and all its member proteins bind
      siroheme and ferredoxin. Insertion of the pyridine nucleotide disulfide
      oxidoreductase domain seemed to be the critical point for the electron transfer
      pattern change in this group. The proteins belonging to group 3 are all flavin
      enzymes, and they bind flavin adenine dinucleotide (FAD) or flavin mononucleotide
      (FMN). Types of electron transfer in this group are divergent, but there are two
      common characteristics. NAD(P)H works as an electron donor or acceptor, and FAD
      or FMN transfers electrons from/to NAD(P)H. Electron transfer functions might be
      added to these common characteristics by the addition of functional domains
      through the evolution of group 3 proteins. Based on the phylogenetic analyses in
      this study and previous studies, we inferred the phylogeny of the energy
      metabolism systems as follows: photosynthesis (and possibly aerobic respiration)
      and the sulfur/nitrogen assimilation system first diverged, then the
      sulfur/nitrogen dissimilation system was produced from the latter system.

PMID- 15486692
TI  - Gene conversion and functional divergence in the beta-globin gene family.
AB  - Different models of gene family evolution have been proposed to explain the
      mechanism whereby gene copies created by gene duplications are maintained and
      diverge in function. Ohta proposed a model which predicts a burst of
      nonsynonymous substitutions following gene duplication and the preservation of
      duplicates through positive selection. An alternative model, the duplication
      degeneration-complementation (DDC) model, does not explicitly require the action
      of positive Darwinian selection for the maintenance of duplicated gene copies,
      although purifying selection is assumed to continue to act on both copies. A
      potential outcome of the DDC model is heterogeneity in purifying selection among
      the gene copies, due to partitioning of subfunctions which complement each other.
      By using the d(N)/ d(S) (omega) rate ratio to measure selection pressure, we can
      distinguish between these two very different evolutionary scenarios. In this
      study we investigated these scenarios in the beta-globin family of genes, a
      textbook example of evolution by gene duplication. We assembled a comprehensive
      dataset of 72 vertebrate beta-globin sequences. The estimated phylogeny suggested
      multiple gene duplication and gene conversion events. By using different programs
      to detect recombination, we confirmed several cases of gene conversion and
      detected two new cases. We tested evolutionary scenarios derived from Ohta's
      model and the DDC model by examining selective pressures along lineages in a
      phylogeny of beta-globin genes in eutherian mammals. We did not find significant
      evidence for an increase in the omega ratio following major duplication events in
      this family. However, one exception to this pattern was the duplication of gamma
      globin in simian primates, after which a few sites were identified to be under
      positive selection. Overall, our results suggest that following gene
      duplications, paralogous copies of beta-globin genes evolved under a nonepisodic
      process of functional divergence.

PMID- 15486693
TI  - Phylogenetic timing of the fish-specific genome duplication correlates with the
      diversification of teleost fish.
AB  - For many genes, ray-finned fish (Actinopterygii) have two paralogous copies,
      where only one ortholog is present in tetrapods. The discovery of an additional,
      almost-complete set of Hox clusters in teleosts (zebrafish, pufferfish, medaka,
      and cichlid) but not in basal actinopterygian lineages ( Polypterus) led to the
      formulation of the fish-specific genome duplication hypothesis. The phylogenetic
      timing of this genome duplication during the evolution of ray-finned fish is
      unknown, since only a few species of basal fish lineages have been investigated
      so far. In this study, three nuclear genes ( fzd8, sox11, tyrosinase) were
      sequenced from sturgeons (Acipenseriformes), gars (Semionotiformes), bony tongues
      (Osteoglossomorpha), and a tenpounder (Elopomorpha). For these three genes, two
      copies have been described previously teleosts (e.g., zebrafish, pufferfish), but
      only one orthologous copy is found in tetrapods. Individual gene trees for these
      three genes and a concatenated dataset support the hypothesis that the fish
      specific genome duplication event took place after the split of the
      Acipenseriformes and the Semionotiformes from the lineage leading to teleost fish
      but before the divergence of Osteoglossiformes. If these three genes were
      duplicated during the proposed fish-specific genome duplication event, then this
      event separates the species-poor early-branching lineages from the species-rich
      teleost lineage. The additional number of genes resulting from this event might
      have facilitated the evolutionary radiation and the phenotypic diversification of
      the teleost fish.

PMID- 15486694
TI  - Diversity of guanylate cyclase-activating proteins (GCAPs) in teleost fish:
      characterization of three novel GCAPs (GCAP4, GCAP5, GCAP7) from zebrafish (Danio
      rerio) and prediction of eight GCAPs (GCAP1-8) in pufferfish (Fugu rubripes).
AB  - The guanylate cyclase-activating proteins (GCAPs) are Ca(2+)-binding proteins of
      the calmodulin (CaM) gene superfamily that function in the regulation of
      photoreceptor guanylate cyclases (GCs). In the mammalian retina, two GCAPs (GCAP
      1-2) and two transmembrane GCs have been identified as part of a complex
      regulatory system responsive to fluctuating levels of free Ca(2+). A third GCAP,
      GCAP3, is expressed in human and zebrafish (Danio rerio) retinas, and a guanylate
      cyclase-inhibitory protein (GCIP) has been shown to be present in frog cones. To
      explore the diversity of GCAPs in more detail, we searched the pufferfish (Fugu
      rubripes) and zebrafish (Danio rerio) genomes for GCAP-related gene sequences
      (fuGCAPs and zGCAPs, respectively) and found that at least five additional GCAPs
      (GCAP4-8) are predicted to be present in these species. We identified genomic
      contigs encoding fuGCAPl-8, fuGCIP, zGCAPl-5, zGCAP7 and zGCIP. We describe
      cloning, expression and localization of three novel GCAPs present in the
      zebrafish retina (zGCAP4, zGCAP5, and zGCAP7). The results show that recombinant
      zGCAP4 stimulated bovine rod outer segment GC in a Ca(2+)-dependent manner. RT
      PCR with zGCAP specific primers showed specific expression of zGCAPs and zGCIP in
      the retina, while zGCAPl mRNA is also present in the brain. In situ hybridization
      with anti-sense zGCAP4, zGCAP5 and zGCAP7 RNA showed exclusive expression in
      zebrafish cone photoreceptors. The presence of at least eight GCAP genes suggests
      an unexpected diversity within this subfamily of Ca(2+)-binding proteins in the
      teleost retina, and suggests additional functions for GCAPs apart from
      stimulation of GC. Based on genome searches and EST analyses, the mouse and human
      genomes do not harbor GCAP4-8 or GCIP genes.

PMID- 15486695
TI  - Evolution and divergence of the genes for cytoplasmic, mitochondrial, and
      flagellar creatine kinases.
AB  - Creatine kinase (CK) plays a central role in energy homeostasis in cells that
      display high and variable rates of energy turnover. A number of CK genes exist,
      each being targeted to particular intracellular compartments. In the vertebrates,
      two genes code for proteins which form homo- and heterodimers targeted to the
      cytoplasm, while two additional genes code for primarily octameric proteins
      targeted to the mitochondrial intermembrane space. Yet another gene is present in
      certain groups which codes for three fused, complete CK domains and is typically
      targeted to the flagellar membrane of primitive-type spermatozoa. CK is widely
      distributed in protochordates and both protostome and deuterostome invertebrate
      groups. The evolutionary relationships of these CK genes have not been fully
      elucidated. The present communication reports new cDNA-derived deduced amino acid
      sequences for four cytoplasmic and three mitochondrial CKs and one flagellar CK
      from lophotrochozoan, protostome invertebrates as well as a new cytoplasmic CK
      sequence from a protochordate tunicate. These new sequences, coupled with
      available sequences in the databases and sequences extracted from genome
      sequencing projects, provide revealing insights into the evolution and divergence
      of CK genes. Phylogenetic analyses showed that single cytoplasmic, mitochondrial,
      and flagellar CK genes were present prior to the divergence of the protostomes
      and deuterostomes. The flagellar CK gene may have evolved within the cytoplasmic
      gene clade, although the evidence is somewhat equivocal. The two cytoplasmic
      genes in the vertebrates, and most likely the two mitochondrial genes, evolved
      after the divergence of the craniates from the protochordates. Comparison of the
      structure of the genes for selected cytoplasmic, mitochondrial, and flagellar CKs
      revealed two identical intron boundaries, further reinforcing the notion of a
      common evolutionary origin, but also showed patterns of changes in structure
      consistent with each gene type. These studies show that the cytoplasmic,
      mitochondrial, and flagellar CK genes are rather ancient and that there has been
      a systematic pattern of duplication and divergence consistent with changing
      nature of energy demands and physicochemical environment in the cells where they
      are expressed.

PMID- 15486696
TI  - Isochore structures in the genome of the plant Arabidopsis thaliana.
AB  - Arabidopsis thaliana is an important model system for the study of plant biology.
      We have analyzed the complete genome sequences of Arabidopsis by using a newly
      developed windowless method for the GC content computation, the cumulative GC
      profile. It is shown that the Arabidopsis genome is organized into a mosaic
      structure of isochores. All the centromeric regions are located in GC-rich
      isochores, called centromere-isochores, which are characterized by a high GC
      content but low gene and T-DNA insertion densities. This characteristic
      distinguishes centromere-isochores from the other class of GC-rich isochores,
      called GC-isochores, which have high gene and T-DNA insertion densities.
      Consequently, 15 isochores have been identified, i.e., 7 AT-isochores, 3 GC
      isochores, and 5 centromere-isochores. The genes in centromere-isochores, which
      have the highest GC content, have much shorter intron lengths and lower intron
      numbers, compared to those of the other two types. There is also considerable
      difference in the numbers and lengths of transposable elements (TEs) between AT
      and GC-isochores, i.e., the TE number (length) of AT-isochores is 6.3 (7.3) times
      that of GC-isochores. It is generally believed that TEs are accumulated in the
      regions surrounding the centromeres. However, within these TE-rich regions, there
      are regions of extremely low TE numbers (TE deserts), which correspond to the
      positions of centromere-isochores. In addition, a heterochromatic knob is located
      at the boundary of an AT-isochore. Furthermore, we show that the differences in
      GC content among isochores are mainly due to the GC content variation of introns,
      the third codon positions and intergenic regions.

PMID- 15486697
TI  - Differential expression of duplicated opsin genes in two eyetypes of ostracod
      crustaceans.
AB  - In the first molecular study of ostracod (Crustacea) vision, we present partial
      cDNA sequences of ostracod visual pigment genes (opsins). We found strong support
      for differential expression of opsins in ostracod median and compound eyes and
      suggest that photoreceptor specific expression may be a general phenomenon in
      organisms with multiple receptors. We infer that eye-specific expression predates
      the divergence of the two species examined, Skogsbergia lerneri and Vargula
      hilgendorfii, because eye-specific opsin orthologs are present in both species.
      We found multiple opsin loci in ostracods, estimating that at least eight are
      present in Skogsbergia lerneri. All opsins from both ostracod species examined
      are more closely related to each other than to any other known opsin sequences.
      Because we find no evidence for gene conversion or alternative splicing, we
      suggest the occurrence of many recent gene duplications. Why ostracods may have
      retained multiple recent opsin gene duplicates is unknown, but we discuss several
      possible hypotheses.

PMID- 15486698
TI  - Origin and evolution of tandem repeats in the mitochondrial DNA control region of
      shrikes (Lanius spp.).
AB  - The origin and evolution of a 128-bp tandem repeat in the mtDNA control region of
      shrikes (Lanius: Aves) were investigated. The tandem repeat is present in only
      two species, L. excubitor and L. ludovicianus. In contrast to the variation in
      repeat number in L. ludovicianus, all individuals of three subspecies of L.
      excubitor had three repeats. Comparative analysis suggests that a short direct
      repeat, and a secondary structure including the tandem repeat and a downstream
      inverted repeat, may be important in the origin of the tandem repeat by slipped
      strand mispairing and its subsequent turnover. Homogenization of repeat sequences
      is most simply explained by expansion and contraction of the repeat array.
      Surprisingly, mtDNA sequences from L. excubitor were found to be paraphyletic
      with respect to L. ludovicianus. These results show the utility of a comparative
      analysis for insights into the evolutionary dynamics of mtDNA tandem repeats.

PMID- 15486699
TI  - Codon usage bias and mutation constraints reduce the level of error minimization
      of the genetic code.
AB  - Studies on the origin of the genetic code compare measures of the degree of error
      minimization of the standard code with measures produced by random variant codes
      but do not take into account codon usage, which was probably highly biased during
      the origin of the code. Codon usage bias could play an important role in the
      minimization of the chemical distances between amino acids because the importance
      of errors depends also on the frequency of the different codons. Here I show that
      when codon usage is taken into account, the degree of error minimization of the
      standard code may be dramatically reduced, and shifting to alternative codes
      often increases the degree of error minimization. This is especially true with a
      high CG content, which was probably the case during the origin of the code. I
      also show that the frequency of codes that perform better than the standard code,
      in terms of relative efficiency, is much higher in the neighborhood of the
      standard code itself, even when not considering codon usage bias; therefore
      alternative codes that differ only slightly from the standard code are more
      likely to evolve than some previous analyses suggested. My conclusions are that
      the standard genetic code is far from being an optimum with respect to error
      minimization and must have arisen for reasons other than error minimization.

PMID- 15486700
TI  - Error in estimation of rate and time inferred from the early amniote fossil
      record and avian molecular clocks.
AB  - The best reconstructions of the history of life will use both molecular time
      estimates and fossil data. Errors in molecular rate estimation typically are
      unaccounted for and no attempts have been made to quantify this uncertainty
      comprehensively. Here, focus is primarily on fossil calibration error because
      this error is least well understood and nearly universally disregarded. Our
      quantification of errors in the synapsid-diapsid calibration illustrates that
      although some error can derive from geological dating of sedimentary rocks, the
      absence of good stem fossils makes phylogenetic error the most critical. We
      therefore propose the use of calibration ages that are based on the first
      undisputed synapsid and diapsid. This approach yields minimum age estimates and
      standard errors of 306.1 +/- 8.5 MYR for the divergence leading to birds and
      mammals. Because this upper bound overlaps with the recent use of 310 MYR, we do
      not support the notion that several metazoan divergence times are significantly
      overestimated because of serious miscalibration (sensuLee 1999). However, the
      propagation of relevant errors reduces the statistical significance of the pre-K
      T boundary diversification of many bird lineages despite retaining similar point
      time estimates. Our results demand renewed investigation into suitable loci and
      fossil calibrations for constructing evolutionary timescales.

PMID- 15486701
TI  - Association of misexpression with sterility in hybrids of Drosophila simulansand
      D. mauritiana.
AB  - Recent studies have identified genes associated with hybrid sterility and other
      hybrid dysfunctions, but the consequences of introgressions of these "speciation
      genes" are often poorly understood. Previously, we identified a panel of genes
      that are underexpressed in sterile male hybrids of Drosophila simulans and D.
      mauritiana relative to pure species. Here, we build on this reverse-genetics
      approach to demonstrate that the underexpression of at least five of these genes
      in hybrids is associated with hybrid sterility and that these five genes are
      coordinately regulated. We map one upstream regulator of these genes to a region
      previously shown to harbor one or more factors causing hybrid sterility. Finally,
      we show that the genes underexpressed in hybrids are often highly conserved, as
      might be predicted for downstream targets of the genetic changes that cause
      hybrid sterility. This approach integrates forward genetics with reverse genetics
      to show a proximate consequence of the introgression of particular hybrid
      sterility-conferring regions between species: underexpression of genes necessary
      for normal spermatogenesis.

PMID- 15486704
TI  - Comparison of fructose-1,6-bisphosphatase gene (fbp) sequences for the
      identification of Lactobacillus rhamnosus.
AB  - Comparative analysis of fructose-1,6-bisphosphatase gene (fbp) sequences was
      evaluated for the differentiation of reference and clinical strains of
      Lactobacillus rhamnosus. The sequences of 1,971 nucleotides of the fbp gene were
      determined on both DNA strands for 21 L. rhamnosus strains, representing
      reference, probiotic, and clinical strains. No PCR amplification of the fbp gene
      was observed for other species of the Lactobacillus casei complex (L. casei and
      L. zeae) or strains of Lactobacillus acidophilus, Streptococcus thermophilus, and
      Escherichia coli. Phylogenetic analysis of the fbp putative amino acid sequences
      of L. rhamnosus strains by the neighbor-joining method showed clear distinct
      positions of this species. The phylogenetic tree, derived from fbp nucleotide
      sequences, showed four clear divisions between strains of L. rhamnosus. From a
      taxonomic point of view, our results confirm for the first time that fbp gene
      sequences have high discriminating power for strains of L. rhamnosus that are
      difficult to differentiate.

PMID- 15486705
TI  - Effect of chromium(VI) action on Arthrobacter oxydans.
AB  - Arthrobacter species is of interest because of its high potential for
      bioremediation. Bacteria can detoxify chromium, by either reduction or
      accumulation inside the bacteria and/or absorption of chromium(VI) (CrVI) on
      their surface, and efflux pump. The possible pathway of Cr(VI) reduction by
      Arthrobacter oxydans isolated from Columbia basalt rocks at a US DOE highly
      contaminated site (USA) has been considered in the present study. FTIR absorption
      spectroscopy showed that these bacteria reduce Cr(VI). In the present study the
      threshold Cr(VI) nontoxic concentration (35 microg/mL) for A. oxydans growing in
      liquid medium was estimated. Complete uptake of this concentration was achieved
      in about 10 days after chromium addition into the medium. At this concentration
      an increase in the protein isolated from the cell wall of A. oxydans was
      observed. This increased protein predominated independently of the growth phase
      at which Cr(VI) was added. Thermal analysis was used to identify any influence of
      Cr(VI) on the DNP complex of A. oxydans. According to the data obtained it can be
      supposed that Cr(VI) reduction predominantly occurs on the bacterial surface and
      that cell wall represents a permeable barrier for these bacteria at the non-toxic
      chromium action.

PMID- 15486706
TI  - Isolation and characterization of genes encoding thermoactive and thermostable
      dextranases from two thermotolerant soil bacteria.
AB  - Thermotolerant Paenibacillus strain Dex70-1B and unidentified strain Dex70-34
      produce thermoactive dextran-degrading enzymes. Plasmid-based genomic DNA
      libraries constructed from mixed bacterial cultures containing Dex70-1B or Dex70
      34 were screened for the ability to confer dextranolytic activity at 70 degrees C
      onto Escherichia coli. One gene, designated dex1, was isolated from each strain.
      The Dex70-1B and Dex70-34 dex1 gene sequences were non-identical, and encoded
      proteins containing 597 (M(r) 68.6 kDa) and 600 amino acids (M(r) 69.2 kDa),
      respectively. The Dex1 amino acid sequences were most similar to one another, and
      formed a new clade among the family 66 glycosyl hydrolase sequences. Expression
      of the Dex1 proteins in E. coli produced dextranolytic activity that converted
      ethanol-insoluble blue dextran into an ethanol-soluble form, suggestive of
      endodextranases (EC 3.2.1.11). Both enzymes were most active at about 60 degrees
      C and pH 5.5, and retained more than 70% maximal activity after incubation at 57
      degrees C for 9.5 h in the absence of substrate.

PMID- 15486707
TI  - Mutants of Agrobacterium tumefaciens virG gene that activate transcription of vir
      promoter in Escherichia coli.
AB  - The virA and virG two-component regulatory system is essential for
      transcriptional activation of virulence (vir) genes in Agrobacterium tumefaciens
      in the presence of inducer molecules. The VirA/VirG mediated vir gene
      transcription depends on a specific interaction between the C-terminal domain of
      the alpha subunit (RpoA) of A. tumefaciens RNA polymerase (RNAP) and N-terminal
      domain of the VirG. However, such interaction does not occur between RNAP of E.
      coli and the VirG, thus vir gene activation in E. coli requires the presence of
      rpoA gene from A. tumefaciens. In this report, we describe VirG mutants that are
      capable of activating the expression of vir genes in E. coli in the absence of A.
      tumefaciens RpoA. The selected 45 VirG mutants exhibited a common amino acid
      substitution at position 56 and additional one or more substitutions at different
      positions; thus the amino acid at position 56 is likely to play a key role in the
      interaction with the RpoA of E. coli. Furthermore, two virG mutants, with amino
      acid substitutions of G56V/V7I/I106N and G56V/I77V, respectively, are capable of
      activating vir genes in E. coli in response to inducer acetosyringone in a virA
      dependent manner, demonstrating that the interaction site between VirG and RpoA
      is separable from that of VirG and VirA. Therefore, it is possible to establish
      inducer-mediated vir gene expression in heterologous hosts using virG mutants
      that are capable of interacting with the RpoA of the respective bacterial hosts
      while retaining the ability to interact with the sensor VirA.

PMID- 15486708
TI  - Nutritional requirements of Lactobacillus delbrueckii subsp. lactis in a
      chemically defined medium.
AB  - This study was undertaken to determine the nutritional requirements of
      Lactobacillus delbrueckii subsp. lactis and to develop a minimal chemically
      defined medium that supports sustained growth of these microorganisms. The single
      omission technique was applied to each component of complete chemically defined
      medium in order to determine the nutritional requirements. L. delbrueckii subsp.
      lactis was prototrophic for alanine, glycine, aspartic acid, asparagine,
      glutamine, threonine, and proline. The lysine requirement was strain-dependent.
      Magnesium was the only essential oligoelement. These microorganisms also required
      uracil and guanine and adenine as pyrimidine and purine sources, respectively. In
      view of the nutritional requirements we designed a new minimal defined medium
      which supports sustained growth of L. delbrueckii subsp. lactis. This medium is
      simple and well defined, and should be preferable to complex media for conducting
      future biochemical, physiological, and genetic studies on L. delbrueckii subsp.
      lactis.

PMID- 15486709
TI  - Analysis of TNT (2,4,6-trinitrotoluene)-inducible cellular responses and stress
      shock proteome in Stenotrophomonas sp. OK-5.
AB  - In this study, the cellular responses of Stenotrophomonas sp. OK-5 to explosive
      2,4,6-trinitrotoluene (TNT) have been extensively analyzed. The stress shock
      proteins, which might contribute to enhancing cellular resistance to TNT-mediated
      toxicity, were induced at different concentrations of TNT used as a substrate for
      cell culture of Stenotrophomonas sp. OK-5 capable of utilizing TNT. Proteomic
      analysis for 2-DE of soluble protein fractions from the culture of OK-5 exposed
      to TNT demonstrated approximately 300 spots on the silver-stained gel ranging
      from pH 3 to pH 10. Among them, 10 spots significantly induced and expressed in
      response to TNT were selected and analyzed. As the result of internal amino acid
      sequencing with ESI-Q TOF mass spectrometry, TNT-mediated stress shock proteins
      such as DnaK, OmpW, and OsmC were identified and characterized. Survival of
      strain OK-5 was periodically monitored in the presence of different
      concentrations of TNT along with the production of the stress shock proteins.
      Cells of strain OK-5 pre-exposed to TNT had in improved survival tolerance.
      Analysis of total cellular fatty acids in strain OK-5 suggested that several
      saturated or unsaturated fatty acids might increase or decrease under TNT
      mediated stress condition. Scanning electron microscopy of cells treated with 0.8
      mM TNT for 12 h revealed irregular rod shapes with wrinkled surfaces.

PMID- 15486710
TI  - Thermo-osmoregulation of heat-labile enterotoxin expression by Escherichia coli.
AB  - Enterotoxigenic Escherichia coli causes diarrhea by producing several virulence
      factors including heat-labile enterotoxin (LT). LT is maximally expressed at 37
      degrees C. The histone-like nucleoid structuring protein (H-NS) appears to
      inhibit LT expression by binding to a downstream regulatory element (DRE) at low
      temperatures. An hns+ E. coli strain, X7026, carrying an LT-beta-galactosidase
      translational fusion plasmid (pLT-lac) was shown to be responsive to varying
      amounts of sodium chloride (NaCl) as well as sucrose or lithium chloride. Maximal
      responsiveness to the various osmolytes was obtained with cells grown at 37
      degrees C under microaerophilic conditions. Temperature-osmotic upshift
      experiments demonstrate LT expression is thermo-osmoregulated. pLT-lac was tested
      in an hns strain or its congenic hns+ strain for its response to NaCl. LT
      expression is elevated in the hns strain regardless of NaCl concentration and
      retains its osmoresponsiveness. The response of the DRE deletion plasmid (pLT
      lacDeltaNC) to NaCl is similar to that of the undeleted plasmid.

PMID- 15486711
TI  - Effect of dipeptides on the growth of Oenococcus oeni in synthetic medium
      deprived of amino acids.
AB  - Oenococcus oeni has numerous amino acid requirements for growth and dipeptides
      could be important for its nutrition. In this paper the individual or combined
      effect of dipeptides on growth of O. oeni X2L in synthetic media deficient in one
      or more amino acids with L-malic acid was investigated. Utilization of
      dipeptides, glucose, and L-malic acid was also analyzed. Dipeptides were
      constituted by at least one essential amino acid for growth. Dipeptides
      containing two essential amino acids, except leucine, had a more favorable effect
      than free amino acids on the growth rate. Gly-Gly was consumed to a greater
      extent than Leu-Leu and a rapid exodus of glycine to the extracellular medium
      accompanied it. The microorganism could use glycine in exchange for other
      essential amino acids outside the cell, favoring growth. In the presence of Leu
      Leu, the increase in glucose consumption rate could be related to the additional
      energy required for dipeptide uptake.

PMID- 15486712
TI  - Molecular characterization and transcription of the luxS gene that encodes LuxS
      autoinducer 2 synthase in Streptococcus bovis.
AB  - Presence of the luxS gene that encodes LuxS autoinducer 2 (AI-2) synthase in
      Streptococcus bovis was demonstrated, and the molecular properties and
      transcription of the gene were examined. The S. bovis luxS was transcribed in a
      monocistronic fashion. Intracellular luxS-mRNA increased sharply during the
      initial exponential growth, and decreased abruptly after the middle exponential
      phase. The large drop in luxS transcription began before the glucose supply to
      cells decreased or the growth rate declined. Transcription of luxS was not
      directly related to cell density, and continued at a maximal rate when cells were
      kept growing at a maximal rate. It is conceivable that AI-2 activity in S. bovis
      acts as a signal for adjusting cell physiology and metabolism in response to
      environmental conditions. However, the role of LuxS in S. bovis, including the
      regulation of AI-2 synthesis,, remains to be clarified.

PMID- 15486713
TI  - Indirect immunofluorescence microscopy for direct detection of Xylella fastidiosa
      in xylem sap.
AB  - The plant pathogen Xylella fastidiosa is the causative agent of a number of
      diseases of economically important crops, including Pierce's disease that affects
      grapevines. Using a commercially available antibody specific for X. fastidiosa,
      we have established a protocol for microscopic identification of the bacterium by
      indirect immunofluorescence. This antibody clearly labels an uncharacterized
      antigen concentrated at a single pole of X. fastidiosa cells, but does not react
      with a non- Xylella control. This technique was also performed successfully on
      xylem exudates from several different plant genera and correlated well with
      standard enzyme-linked immunosorbent assay tests. These results establish a novel
      method for in situ assessment of X. fastidiosa infection from host plants.

PMID- 15486714
TI  - Fatty acid composition of planktonic species of Anabaena (cyanobacteria) with
      coiled trichomes exhibited a significant taxonomic value.
AB  - Twenty-six axenic strains of planktonic Anabaena with coiled trichomes belonging
      to 13 species were investigated by analyzing the pattern and content of their
      fatty acid composition, and by comparing their fatty acid composition with their
      morphological properties. In general, the planktonic Anabaena with coiled
      trichomes contained 14:0, 16:0, 16:1(cis-), 18:0, 18:1, 18:2, and 18:3(alpha) as
      their major fatty acid component, and were classified as Type 2 according to the
      Kenyon-Murata System. The Type 2 was further divided into two subtypes: Type 2A
      with 16:2 and 16:3, and Type 2B without 16:2 and 16:3. Among these Anabaena
      strains with coiled form, A. oumiana (NIES-73 and Ana Kas1) and A. eucompacta
      (Ana Chiba) contained Type 2B fatty acid composition, and other strains contained
      Type 2A. Among the strains with the latter type, A. circinalis (Ana Da) and A.
      curva (Ana Ao) had low levels of 18:3(alpha). Most Anabaena strains with coiled
      trichomes showed a strong correlation between morphological characteristics and
      fatty acid composition.

PMID- 15486739
TI  - Oncologic and functional results of total mesorectal excision and autonomic nerve
      preserving operation for advanced lower rectal cancer.
AB  - PURPOSE: Total mesorectal excision contains two different procedures: autonomic
      nerve preservation, and autonomic nerve sacrifice. It is unclear whether
      autonomic nerve preservation is suitable curative procedure. We clarify the
      significance of autonomic nerve preservation for an advanced lower rectal cancer.
      METHODS: All 403 patients curatively resected between 1975 and 1999 were
      clinicopathologically studied. Between 1975 and 1984, all patients routinely
      received total mesorectal excision without autonomic nerve preservation (TME-P(-)
      group). Since 1985, total mesorectal excision with autonomic nerve preservation
      has been performed in 81 percent of patients (TME-P(+) group). The remaining
      patients received TME-P(-) because of suspicious invasion to autonomic nerve
      plexus. All clinical and pathologic data were entered into a computer database.
      Long-term follow-up was used to analyze the oncologic and functional results of
      TME-P(+) group compared with TME-P(-) group. RESULTS: The follow-up rate was 98.1
      percent. In either Dukes A+B or Dukes C disease, the TME-P(+) group did not
      increase local recurrence or decrease ten-year disease-free survival compared
      with the TME-P(-) group of Period 1975 to 1984. The TME-P(-) group of Period 1985
      to 1999 had the highest distant metastasis and the lowest survival rates than any
      other groups. Urinary or sexual function was well preserved in the TME-P(+)
      group. CONCLUSIONS: Autonomic nerve preservation is oncologically and
      functionally excellent and suitable for almost all patients with advanced lower
      rectal cancer. Intensive chemotherapy is needed for patients whose autonomic
      nerves were killed in suspicion of nerve invasion.

PMID- 15486738
TI  - POSSUM, p-POSSUM, and Cr-POSSUM: implementation issues in a United States health
      care system for prediction of outcome for colon cancer resection.
AB  - PURPOSE: The Physiologic and Operative Severity Score for the enUmeration of
      Mortality and morbidity (POSSUM), Portsmouth revision (p)-POSSUM, and colorectal
      (Cr)-POSSUM scoring systems were developed as audit tools for comparing outcomes
      in surgical and colorectal patients on the basis of operative risk assessment.
      The aim of this study was to evaluate the applicability of these systems to a
      cohort of colon cancer patients undergoing surgery in the United States. METHODS:
      POSSUM factors from 890 consecutive patients undergoing major surgical procedures
      for colon cancer in nine United States hospitals over a two-year period from
      January 2000 through December 2001 were prospectively collected. The observed
      over the expected hospital mortality was compared by means of the POSSUM, p
      POSSUM, and Cr-POSSUM scoring systems. The effect of missing data on the utility
      of this process for outcome assessment was assessed with three methods for data
      imputation. RESULTS: The number of resections per institution ranged from 13 to
      437. The observed mortality rate ranged from 0.8 percent to 15.4 percent among
      the institutions, with an overall operative mortality of 2.3 percent. The POSSUM,
      p-POSSUM, and Cr-POSSUM predicted mortality was 10.7 percent, 11.2 percent, and
      4.9 percent, respectively. The POSSUM and p-POSSUM models overpredicted mortality
      in all institutions ( P < 0.01), whereas the Cr-POSSUM demonstrated an observed
      over expected hospital mortality ratio of >1 in three institutions. The
      calculations were unaffected by the various methods of inserting missing data.
      CONCLUSION: An apparent overprediction of mortality for colon cancer resection
      was evident with all three POSSUM variants. This implies that a calibration
      process is required for use of these variants in the United States health care
      system. Missing data may be treated as normal values without influencing outcome.
      The Cr-POSSUM appeared to be the most promising audit tool for colorectal cancer
      surgery; however, it will require further refinement to provide process control
      graphs for identification of potential outliers and improvement in the quality of
      care in the United States.

PMID- 15486740
TI  - Long-term functional outcome of low anterior resection with colonic J-pouch
      reconstruction for rectal cancer in the elderly.
AB  - PURPOSE: Bowel function after low anterior resection for rectal cancer with
      colonic J-pouch reconstruction is more normal than after conventional straight
      anastomosis. However, few reports have examined the function of colonic J-pouch
      reconstruction in the elderly. Good function would obviate the need for
      colostomy, which is sometimes performed because of concern about fecal
      incontinence, which increases with age. This study evaluated the function of
      colonic J-pouch reconstruction in elderly patients aged 75 years or older.
      METHODS: Functional outcome was compared in 20 patients aged 75 years or older
      (older group) and 27 patients aged 60 to 74 years (old group) and 60 patients
      aged 59 years or younger (young group), 3 years after colonic J-pouch
      reconstruction, using a functional scoring system with a 17-item questionnaire
      (score range, 0 (overall good) to 26 (overall poor)). RESULTS: The functional
      scores in the three age groups were satisfactory and similar. Among patients with
      anastomoses 1 cm to 4 cm from the anal verge, all 17 categories on the
      questionnaire in the three age groups were similar. Among patients with
      anastomoses 5 cm to 8 cm from the anal verge, only the use of laxatives or
      glycerine enemas was more common in the older group than in the old and young
      group (90 vs. 38.5 percent and 43.3 percent; P = 0.01). CONCLUSIONS: Low anterior
      resection with colonic J-pouch reconstruction provides excellent functional
      outcome, including continence, for elderly patients. Colonic J-pouch
      reconstruction is a highly preferable alternative to permanent colostomy in
      elderly patients undergoing low anterior resection.

PMID- 15486741
TI  - Stents or open operation for palliation of colorectal cancer: a retrospective,
      cohort study of perioperative outcome and long-term survival.
AB  - PURPOSE: Expandable, metallic stents provide a new modality of palliation for
      patients with noncurable metastatic colorectal adenocarcinoma. This study was
      designed to compare the use of expandable metallic stents as a palliative measure
      to traditional open surgical management, with particular reference to length of
      stay, and survival. METHODS: Patients admitted between 1997 and 2002 with left
      sided (splenic flexure and distal), colorectal adenocarcinoma and nonresectable
      metastatic disease (Stage 4) were treated with expandable metal stents or open
      surgery (resection, bypass, or stoma). The group of patients having stents
      inserted were compared with regard to perioperative outcome and survival to those
      having open surgical procedures. RESULTS: Twenty-two of 25 patients had colonic
      stents successfully inserted and 19 patients underwent open surgery. The two
      groups were comparable: stent: median age, 66 (range, 37-88) years; 13 males; and
      open operation: median age, 68 (range, 51-85) years; 12 males. The tumors were
      primary in 22 stents procedures and 18 open operations. The site of obstruction
      was: splenic flexure, 2 stent vs. 0 open operation; descending colon, 2 stent vs.
      2 open operation; sigmoid colon, 12 stent vs. 6 open operation; rectum, 9 stent
      vs. 11 open operation. The American Society of Anesthesiologists (ASA) class was:
      ASA 1, 0 stent vs. 0 open operation; ASA 2, 6 stent vs. 9 open operation; ASA 3,
      15 stent vs. 7 open operation; ASA 4, 4 stent vs. 3 open operation. The open
      operations were laparotomy only (n = 2), bypass (n = 1), stoma (n = 7), resection
      with anastomosis (n = 4), resection without anastomosis (n = 5). The
      complications after open operation were urinary (n = 2), stroke (n = 1), cardiac
      (n = 2), respiratory (n = 2), deep vein thrombosis (n = 1), anastomotic leak (n =
      1). There were no stent-related complications. The mean length of stay was
      significantly shorter in the stent group (4 vs. 10.4 days; P < 0.0001). There was
      no difference in survival between the two groups (median survival: stent group,
      7.5 months; open operation, 3.9 months; log-rank P value = 0.2156). CONCLUSIONS:
      Patients treated with stents are discharged earlier than after open surgery.
      Stents do not affect survival. Expandable metal stents provide an acceptable
      alternative and may be better than traditional open surgical techniques.

PMID- 15486742
TI  - Flat lesions of the colorectal mucosa: differences in recognition between
      Japanese and American endoscopists.
AB  - INTRODUCTION: Flat lesions of the colorectal mucosa have been a topic of debate
      since they were first described. Japanese series suggest that flat adenomas
      represent up to 25 percent of all colorectal adenomas and that they are a
      particularly advanced form of neoplasia for their size. Series published by
      Western endoscopists show a lower incidence and a lower degree of dysplasia. We
      performed this study to see whether American colonoscopists interpret the shape
      of lesions of the colorectal mucosa differently from their Japanese colleagues.
      METHODS: A book of endoscopic photographs of 50 small lesions of the colorectal
      mucosa was shown to 11 American and 8 Japanese colonoscopists. The colonoscopists
      were asked to decide whether each lesion was sessile, flat, depressed,
      pedunculated, or that there was no polyp present. Results were tabulated by
      lesion and by endoscopist. RESULTS: Although the average number of lesions deemed
      sessile was similar between groups (American, 33.8 +/- 2.1 95 percent confidence
      interval; Japanese, 29.4 +/- 2.2) there were marked differences in determination
      of flat lesions (American, 5.3 +/- 1.5; Japanese, 14.5 +/- 2.2), depressed
      lesions (American, 0.8 +/- 0.4; Japanese, 2.4 +/- 0.7) and those deemed "no
      polyp" (American, 5.1 +/- 0.9; Japanese 0). At least six of the eight Japanese
      colonoscopists agreed that a particular lesion was flat on 12 occasions, but
      American colonoscopists agreed on only 1 of these. Six of eight Japanese
      colonoscopists agreed on lesions as sessile in 27 cases, with Americans agreeing
      in 25 of these. CONCLUSIONS: There are significant differences in interpretation
      of the shape of lesions of the colorectal mucosa between Japanese colonoscopists
      and their American counterparts. These differences are likely to account for some
      of the apparent differences in incidence in series of flat colorectal adenomas
      reported from Japan and Western countries.

PMID- 15486743
TI  - Association between recurrence of sporadic colorectal cancer, high level of
      microsatellite instability, and loss of heterozygosity at chromosome 18q.
AB  - PURPOSE: Microsatellite instability and loss of heterozygosity of chromosomes
      18q, 8p, and 4p are genetic alterations commonly found in colorectal cancer. We
      investigated whether these genetic markers allow for the stratification of
      patients with Stage II to III colorectal cancer into groups with different
      recurrence risks, and with different prognoses. METHODS: Tumors of 113 patients
      were evaluated for loss of heterozygosity of chromosomes 18q, 8p, and 4p and for
      microsatellite instability by use of six microsatellite markers. Genetic
      alterations involving each of these genetic markers were examined for association
      with disease recurrences and survival. RESULTS: Loss of heterozygosity of
      chromosomes 18q, informative in 96 percent of cases, in Stage III tumors was
      associated with higher risk of overall recurrence ( P< 0.001), local recurrence (
      P< 0.001), distant metastases ( P< 0.001), decreased overall survival ( P=
      0.002), and disease-free survival ( P< 0.001). The recurrence rates and survival
      rates among patients with Stage II colorectal cancer were independent of loss of
      heterozygosity of chromosome 18q. Stage III and loss of heterozygosity of
      chromosome 8p also were associated with a higher risk of recurrences when these
      factors were considered individually. In multivariate analysis, only loss of
      heterozygosity of chromosome 18q was independently associated with risk of
      recurrences ( P < 0.001) and with disease-free survival ( P= 0.001). No
      correlation was observed between microsatellite instability and recurrence rates.
      However, microsatellite instability was associated with improved overall survival
      ( P= 0.04) and with a longer disease-free interval ( P= 0.002). Only in five
      cases (16.7 percent) was it possible to perform resection of recurrences; two of
      these patients had microsatellite instability tumor. In no cases was it possible
      to resect recurrence of tumors with loss of heterozygosity of chromosome 18q.
      CONCLUSIONS: Loss of heterozygosity of chromosome 18q is an informative genetic
      marker, which in resected Stage III colorectal cancer can be used to predict
      recurrences and survival. Microsatellite instability identified cases that, even
      in the case of recurrence, have a more favorable prognosis.

PMID- 15486744
TI  - Anorectal pathology in HIV/AIDS-infected patients has not been impacted by highly
      active antiretroviral therapy.
AB  - PURPOSE: The aim of this study was to determine if the prevalence and
      distribution of anorectal pathology in HIV-infected patients treated by
      colorectal surgeons have changed after the introduction of highly active
      antiretroviral therapy. METHODS: The Los Angeles County-University of Southern
      California HIV Clinic is solely dedicated to the care of HIV patients. A
      colorectal clinic was established within this environment in 1991 and has served
      as the exclusive provider for the care of anorectal pathology in these patients.
      A prospective database of patients treated at this clinic was reviewed for two 18
      month periods. The first group (early period) was composed of patients treated
      between January 1994 through June 1995, before the institution of more effective
      antiretroviral therapy. The second group (later period) consisted of patients
      treated between January 2001 through June 2002, after the introduction of highly
      active antiretroviral therapy. Data were tabulated for HIV-related anorectal
      pathologies, such as anal ulcer and anogenital condyloma, and non-HIV-related
      pathologies, including fissure, fistula in ano, hemorrhoids, perianal abscess,
      and other pathologies, for each of the two time periods. RESULTS: A total of 117
      individual patients with anorectal pathology were treated in the early period and
      109 received care in the later period, of which 107 were able to be evaluated.
      The pathology was distributed as follows for the early vs. late periods: 33 vs.
      33 percent for ulcer, 30 vs. 34 percent for condyloma, 9 vs. 4 percent for
      fissure, 6 vs. 6 percent for fistula, 4 vs. 5 percent for hemorrhoids, 3 vs. 3
      percent for abscess, and 15 vs. 16 percent for all other anorectal pathology.
      There was no statistically significant difference in any of these groups.
      CONCLUSION: The prevalence and distribution of both HIV-related and non-HIV
      related anorectal pathology seen in our HIV patients have not been altered by the
      introduction of highly active antiretroviral therapy.

PMID- 15486745
TI  - Rectal complications after prostate brachytherapy.
AB  - PURPOSE: Prostate brachytherapy is gaining wide popularity as an alternative to
      resection for the treatment of locally advanced prostate cancer. Rectal-urethral
      fistula after prostate brachytherapy is a rare but serious complication, and its
      incidence, presentation, risk factors, and clinical management have not been well
      described. METHODS: From January 1997 to October 2002, seven patients with rectal
      urethral fistulas were referred to two institutions (Brigham and Women's Hospital
      and West Roxbury Veteran's Administration Hospital) of a major teaching referral
      center. Clinical presentation, risk factors, prostate staging, and clinical
      management were examined in a retrospective fashion. RESULTS: Seven rectal
      urethral fistulas developed from roughly 700 (1 percent) patients treated with
      prostate brachytherapy for prostate cancer. The average patient age was 67.7
      years, preimplant prostate-specific antigen was 7.1, and Gleason score was 3+3.
      Symptoms occurred at a mean of 27.3 months after prostate brachytherapy was
      started and included anorectal pain (57 percent), clear mucous discharge (57
      percent), diarrhea (43 percent), and rectal ulceration (43 percent). Coronary
      artery disease was a common comorbidity (71 percent). Previous transurethral
      resection of prostate (28 percent) and pelvic irradiation or external beam
      radiation therapy (14 percent) were not associated with increased risk of rectal
      urethral fistula. All patients underwent a diverting colostomy (86 percent) or
      ileostomy (14 percent), and four patients went on to have definitive therapy.
      Definitive resection was performed between 5 and 43 months after diverting ostomy
      and was chosen on the basis of comorbid disease, quality of life, and degree of
      operation. Two patients required a second diversion after definitive resection
      because of anorectal pain and a colocutaneous fistula. Postoperative
      complications included myocardial infarction (14 percent), blood transfusion (14
      percent), and bowel perforation (14 percent). Patients became symptom-free nine
      months after surgery. Six patients are alive and well today; one died from an
      unrelated cause. CONCLUSIONS: Rectal-urethral fistula after prostate
      brachytherapy is a rare but devastating complication. Patients should be followed
      for at least three years after prostate brachytherapy because symptoms can
      develop late in the course. Although diversion of fecal stream does not heal the
      fistula, all patients diagnosed with rectal-urethral fistula should first undergo
      diverting ostomy to alleviate symptoms. Then, one should consider definitive
      resection and ostomy closure.

PMID- 15486746
TI  - Thrombosed external hemorrhoids: outcome after conservative or surgical
      management.
AB  - PURPOSE: Few data exist on the actual recurrence rates of thrombosed external
      hemorrhoids. We wished to determine the incidence of recurrence, intervals to
      recurrence, and factors predicting recurrence of thrombosed external hemorrhoids
      after conservative or surgical management. METHODS: Two hundred and thirty-one
      consecutive patients with thrombosed external hemorrhoids treated from 1990 to
      2002 were identified. Recurrence was defined as complete resolution of the index
      lesion with subsequent return of a thrombosed external hemorrhoid and did not
      include patients with chronic symptoms. Data were gathered retrospectively.
      Multiple potential risk factors were reviewed. RESULTS: The index thrombosed
      external hemorrhoid was managed conservatively in 51.5 percent of cases and
      surgically in 48.5 percent. There were no differences between groups in gender,
      age, or race, and 44.5 percent of all patients had a prior history of thrombosed
      external hemorrhoid. A prior history was less common in the conservative group
      than in the surgical group (38.1 percent vs. 51.3 percent; P < 0.05). The
      frequency of pain or bleeding as the primary complaint was higher in the surgical
      group ( P < 0.001 and P < 0.002). In addition, the surgical group was more likely
      to report all three symptoms of pain, bleeding, and a lump ( P < 0.005). Mean
      follow-up was 7.6 months, with the range extending to 7 years. Time to symptom
      resolution averaged 24 days in the conservative group vs. 3.9 days in the
      surgical group ( P < 0.0001). The overall incidence to recurrence was 15.6
      percent-80.6 percent in the conservative group vs. 19.4 percent in the surgical
      group. The rate of recurrence in the conservative group was 25.4 percent (4/29;
      14 percent were excised) whereas only 6.3 percent of the surgical patients had
      recurrence ( P < 0.0001). Mean time to recurrence was 7.1 months in the
      conservative group vs. 25 months in the surgical group ( P < 0.0001). Survival
      analysis for time to recurrence of thrombosed external hemorrhoid indicated that
      time to recurrence was significantly longer for the surgical group ( P < 0.0001).
      Logistic regression analysis of multiple factors (including diverticular disease,
      constipation, straining, benign prostatic hypertrophy, diarrhea, skin tags,
      history of travel, anoreceptive sex, anal fissures, internal hemorrhoids, and
      obesity) was performed to determine the outcome of each group. None of these
      variables were significant predictors of recurrence. CONCLUSIONS: Patients whose
      initial presentation was pain or bleeding with or without a lump were more like
      to be treated surgically. Surgically treated patients had a lower frequency of
      recurrence and a longer time interval to recurrence than conservatively treated
      patients. None of the variables analyzed were significant predictors of a
      particular treatment, except for a prior history of thrombosed external
      hemorrhoids, which may represent patient choice. Although most patients treated
      conservatively will experience resolution of their symptoms, excision of
      thrombosed external hemorrhoids results in more rapid symptom resolution, lower
      incidence of recurrence, and longer remission intervals.

PMID- 15486747
TI  - Long-term results of balloon catheter dilation of lower gastrointestinal tract
      stenoses.
AB  - PURPOSE: This study involved a prospective evaluation of the results of the
      balloon catheter dilation of lower gastrointestinal stenoses. METHODS: First a
      guide-wire was introduced into the stenosis followed under x-ray control by a
      double-lumen balloon catheter, or directly through the endoscope a balloon
      catheter, with progressive dilation under pressures of 1.5 to 3 atm. The result
      was assessed via the decreased indentation of the balloon and the increased
      diameter of the stenosis. RESULTS: Between January 1985 and November 2002, 133
      dilations were performed on 57 patients. The cause of the stenosis was
      postoperative stenosis in 44 patients, Crohn's disease in 6, ulcerative colitis
      in 2, postirradiative stenosis in 1, ischemic stenosis in 1, and scarring of the
      anus in 3 patients. Four of the stenoses were localized to the anus, 45 to the
      rectum, 7 to the colon, and 1 to the terminal ileum. The average diameter of the
      stenosis was increased from 7.2 (range, 1-14) mm to 19.7 (range, 14-25) mm.
      Colostomies were closed in 11 of 17 cases. In five patients, the ileus state
      ceased, and the three colocutaneous fistulas healed rapidly. In 17 of 57
      patients, reoperation was proposed. In one patient, fever as a complication was
      treated with antibiotics. CONCLUSIONS: The dilation of benign stenoses of the
      lower gastrointestinal tract with a balloon catheter is an effective and safe
      method, which in most cases (70 percent) results in long-term elimination of the
      obstructive symptoms, so that surgery can be avoided.

PMID- 15486748
TI  - Randomized cross-over trial of polyethylene glycol electrolyte solution and water
      for colostomy irrigation.
AB  - PURPOSE: Water for colostomy irrigation is largely absorbed by the colon, which
      may result in less efficient expulsion of stool. This study compared the outcome
      of colonic cleansing with water and polyethylene glycol solution. METHODS: In a
      cross-over study, 41 colostomy irrigators were randomly assigned to water or
      polyethylene glycol solution irrigation first and then the other regimen, each
      for one week. Patients recorded fluid inflow time, total washout time, cramps,
      leakage episodes, number of stoma pouches used, and satisfaction scores (Visual
      Analog Scale, 1-10: 1 = poor, and 10 = excellent). The median and interquartile
      range for each variable was calculated, and the two treatments were compared
      (Wilcoxon's test). RESULTS: Eight patients failed to complete the study. Thirty
      three patients (20 females; mean age, 55 (range, 39-73) years) provided 352
      irrigation sessions: water (n = 176), and polyethylene glycol solution (n = 176).
      Irrigation was performed every 24, 48, and 72 hours by 17, 9, and 7 patients
      respectively, using 500 ml (n = 1), 750 ml (n = 2), 1,000 ml (n = 16), 1,500 ml
      (n = 11), 2,000 ml (n = 2), and 3,500 ml (n = 1) of fluid. The median and
      interquartile range for water vs. polyethylene glycol solution were: fluid inflow
      time (6 (range, 4.4-10.8) vs. 6.3 (range, 4.1-11) minutes; P = 0.48), total
      washout time (53 (range, 33-69) vs. 38 (range, 28-55) minutes; P = 0.01), leakage
      episodes (2.3 (range, 1.7-3.8) vs. 0.7 (range, 0.2-1); P < 0.001), satisfaction
      score (5.8 (range, 4-7.5) vs. 8.8 (range, 8.3-10); P < 0.001), and stoma pouch
      usage per week (75 (range, 45-80) vs. 43 (range, 0-80); P = 0.008). No difference
      was demonstrated for frequency of cramps ( P = 0.24). CONCLUSIONS: Polyethylene
      glycol solution performed significantly better than water and may be a superior
      alternative fluid regimen for colostomy irrigation.

PMID- 15486749
TI  - Perianal abscess: a pilot study comparing packing with nonpacking of the abscess
      cavity.
AB  - PURPOSE: Perianal sepsis is traditionally treated by incision and drainage, with
      packing of the residual cavity until healing. This study was designed to show
      that perianal abscess may be safely treated by incision and drainage alone.
      METHODS: Healing times, analgesic requirements, pain scores, abscess recurrence,
      and fistula rates were compared between two randomized groups treated with and
      without packing of perianal abscess cavities. RESULTS: Fifty patients were
      recruited (7 lost to follow-up): 20 in the packing and 23 in the nonpacking arm.
      The groups were comparable in terms of age and gender distribution, type and size
      of abscess, and the presence of a fistula at operation. Mean healing times were
      similar ( P = 0.214). The rate of abscess recurrence was similar ( P = 0.61).
      Postoperative fistula rates were similar ( P = 0.38). Pain scores at the first
      dressing change were similar ( P = 0.296). Although pain scores appeared much
      reduced in the nonpacking arm, this did not attain statistical significance.
      CONCLUSIONS: Our pilot study indicates that perianal abscesses can be managed
      safely without continued packing of the cavity without any obvious complications.

PMID- 15486750
TI  - Small-bowel infarction from disseminated aspergillosis.
AB  - INTRODUCTION: Despite the use of new, effective drugs, the disseminated invasive
      aspergillosis often remains lethal in neutropenic patients. Diagnosis is
      difficult because early symptoms are nonspecific. New tools could help in
      diagnosis and lead to early surgery when needed. METHODS: A neutropenic patient
      developed an acute abdomen. CT findings were a diffuse, small-bowel distention
      with a thickened, distal, ileum wall. Emergency surgery was performed with
      resection and immediate anastomosis of the distal ileum. Pathology of the small
      bowel showed a wall necrosis and invasion by Aspergillus fumigatus. RESULTS: The
      postoperative course was uneventful except for persisting diarrhea secondary to a
      coexistent infection with Clostridium difficile. Aspergillus antigene in serum
      was positive, whereas neither pulmonary nor central nervous system aspergillosis
      was observed on CT scan. CONCLUSIONS: This diagnosis should be considered when
      neutropenic patients show abdominal pain and distention with fever. Repetition of
      Aspergillus antigenemia, search for others aspergillosis localizations, CT scan,
      and colonoscopy with biopsies should be performed until diagnosis allows the
      administration of early antifungal therapy.

PMID- 15486751
TI  - Eradication of pathogenic bacteria and restoration of normal pouch flora:
      comparison of metronidazole and ciprofloxacin in the treatment of pouchitis.
AB  - PURPOSE: Pouchitis is the major long-term complication after ileal pouch-anal
      anastomosis for ulcerative colitis. Metronidazole and ciprofloxacin are commonly
      used for treatment; however, nothing is known about the effects on the pouch
      flora during and after pouchitis episodes. This study was designed to evaluate
      the effect of both antibiotics on eradication of pathogens and the restoration of
      normal pouch flora. METHODS: The fecal flora obtained from 13 patients with
      ulcerative colitis was examined at the beginning of a pouchitis episode before
      treatment, during treatment with metronidazole or ciprofloxacin, and during
      pouchitis-free periods. Some patients experienced more than one pouchitis
      episode. Therefore, a total of 104 samples was obtained. Each sample was cultured
      under aerobic and anaerobic conditions and the isolated bacteria were identified.
      Furthermore, the clinical response to both antibiotics was compared using the
      Pouchitis Disease Activity Index score. RESULTS: During pouchitis-free periods,
      the patients had a flora characterized by high numbers of anaerobes and no or low
      numbers of pathogens. This flora resembles normal colon flora. During pouchitis
      episodes, we found a significant decrease of anaerobes ( P = 0.01), a significant
      increase of aerobic bacteria ( P = 0.01), and significantly more numbers of
      pathogens, such as Clostridium perfringens (in 95 percent of the samples; P <
      0.01) and hemolytic strains of Escherichia coli (in 57 percent of the samples; P
      = 0.05). Treatment with metronidazole resulted in a complete eradication of the
      anaerobic flora, including C. perfringens. However, no changes in the numbers of
      E. coli were found. In contrast, when the patient was treated with ciprofloxacin,
      not only C. perfringens, but also all coliforms including hemolytic strains of E.
      coli disappeared. The larger part of the anaerobic flora was left undisturbed
      during the administration of ciprofloxacin. Patients treated with ciprofloxacin
      experienced significant larger reductions in Pouchitis Disease Activity Index
      score compared with patients treated with metronidazole ( P = 0.04). CONCLUSIONS:
      This study strongly suggests a role of pathogenic bacteria ( C. perfringens
      and/or hemolytic strains of E. coli) in pouchitis. From a microbiologic and a
      clinical point of view, ciprofloxacin is preferable to metronidazole, because
      treatment with ciprofloxacin eradicates both pathogens and results in an optimal
      restoration of normal pouch flora.

PMID- 15486752
TI  - Management of penetrating colon and rectal injuries in the pediatric patient.
AB  - PURPOSE: Management of civilian penetrating colon injuries in the adult has
      evolved from the universal use of fecal diversion to the highly selective use of
      colostomy. We hypothesized that a similar management approach was appropriate for
      the pediatric population. METHODS: A retrospective review of pediatric patients
      (age <17 years) with a penetrating colorectal injury was performed at six Level I
      trauma centers for the period January 1990 through June 2001. RESULTS: For the
      period of review, 53 children with a penetrating colorectal injury were
      identified. Firearms caused 89 percent of the injuries. The colon was injured in
      83 percent (n = 44) of patients and the rectum in 17 percent (n = 9) of patients.
      The colorectal injury was managed without colostomy in 62 percent (n = 33) and
      with colostomy in 38 percent (colon = 11, rectum = 9). All rectal injuries were
      treated with colostomy. The hospital length of stay was longer in the colostomy
      group (17.6 days vs. 11.4 days). The complication rate was higher in the
      colostomy group (55 percent vs. 27 percent), which included two patients with
      stoma-related complications. There was no mortality in this series. CONCLUSIONS:
      Primary repair was used safely in most cases of civilian penetrating colon
      injuries in the pediatric population. All rectal injuries were treated with
      colostomy in this series. Fecal diversion was used selectively. Colostomy was
      performed for selected cases of colon wounds associated with shock, multiple
      blood transfusions, multiple other injuries, extensive contamination, and high
      velocity weapons. In the absence of these associated factors, primary repair
      appears justified.

PMID- 15486753
TI  - The accuracy of clinical examination in the diagnosis of rectal intussusception.
AB  - PURPOSE: This study was designed to compare routine clinical examination and
      defecography in the diagnosis of rectal intussusception in constipated patients
      and study relationships between rectal intussusception and symptoms. METHODS: A
      total of 127 consecutive patients with functional constipation were examined in
      the left-lateral position with rectal palpation and rectoscopy according to a
      protocol. An overall clinical judgment was made if the patient had
      intussusception, unclear finding, or no intussusception. Defecography was
      performed without knowledge of the results of the clinical evaluation. Symptom
      duration varied between 0.5 to 60 (median, 10) years. All patients fulfilled a
      bowel questionnaire and all had a full physiologic workup. RESULTS: A diagnosis
      by digital examination ( P = 0.002) and by rectoscopy ( P = 0.002) as well as the
      overall judgment ( P = 0.0002) was clearly related to a longer intussusception as
      measured by defecography. Five of six intra-anal intussusceptions were correctly
      assessed by clinical examination, whereas the correlation to defecography was
      poor in the group with short intussusceptions. Neither clinical nor defecographic
      diagnosis of rectal intussusception were related to the main symptoms of
      constipation but both were associated with a tendency toward lower anal resting
      pressures ( P = 0.04 and P = 0.06) and an obtuse anorectal angle (during
      evacuation, P = 0.01 and P = 0.01). CONCLUSIONS: There is no clear relationship
      between rectal intussusception and constipation. However, intussusception is
      related to sphincter function and may be of clinical relevance. A normal clinical
      examination will exclude most long intussusceptions, whereas a positive finding
      needs further evaluation with defecography.

PMID- 15486754
TI  - Management of colonic Dieulafoy lesions with endoscopic mechanical techniques:
      report of two cases.
AB  - Although Dieulafoy lesion is generally located in the proximal stomach, other
      locations have been reported. We present two cases of bleeding colonic Dieulafoy
      in patients with chronic renal failure who were treated with mechanical methods.
      In the first case, an active arterial bleeding without mucosal defect was
      localized in the descending colon. In the second case, a protruding vessel with
      active bleeding was found in the transverse colon. The two patients were
      initially treated with epinephrine and hemostatic clips. In the second patient,
      an endoloop was attached to the base of the previously placed hemoclips because
      of rebleeding. To our knowledge, this is the first case of combined endoscopic
      approach with hemostatic clips and endoloop to treat a colonic Dieulafoy lesion.
      Colonic Dieulafoy lesions reported in the relevant literature and the hemostatic
      treatments used are reviewed.

PMID- 15486755
TI  - Regression of rectal mucosa-associated lymphoid tissue lymphoma but persistence
      of Helicobacter pylori infection of gastric mucosa after administration of
      levofloxacin: report of a case.
AB  - PURPOSE: Several articles have reported regression of rectal lymphoma of mucosa
      associated lymphoid tissue after anti- Helicobacter pylori therapy. It remains
      unclear, however, whether lymphoma of rectal mucosa-associated lymphoid tissue is
      related to Helicobacter pylori infection. METHODS: A 60-year-old woman visited
      our hospital with a complaint of hematochezia. On colonoscopy a pale, ulcerated
      protrusion approximately 3.5 cm in diameter was found in the rectum. Pathologic
      diagnosis of a biopsy specimen was low-grade mucosa-associated lymphoid tissue
      lymphoma. The patient received a ten-day course of levofloxacin, and the cycle
      was repeated three times over seven months. RESULTS: Although persistence of
      Helicobacter pylori infection was confirmed, the tumor regressed completely.
      CONCLUSION: Our findings in this case suggest that rectal lymphoma of mucosa
      associated lymphoid tissue may be related to unknown microorganisms other than
      Helicobacter pylori. Levofloxacin may be effective for treatment of rectal
      lymphoma of mucosa-associated lymphoid tissue regardless of Helicobacter pylori
      infection.

PMID- 15486756
TI  - Second anastomotic recurrence after radical left hemicolectomy: report of a case.
AB  - A number of patients undergoing curative colorectal resection present with local
      recurrences that are not resectable at the time of diagnosis. Whereas these are
      predominantly perianastomotic, only a few are primarily anastomotic occurring at
      the suture line. A 65-year-old female with Dukes B2 adenocarcinoma of the sigmoid
      colon after a radical left hemicolectomy had further resections with stapled
      anastomosis at 12 and 22 months, for primary anastomotic recurrences. She remains
      well 54 months after initial surgery. The recurrent cancers were histologically
      similar and showed no features of microsatellite instability. The
      microenvironment at the anastomosis and the suture material must have contributed
      to this unusual course.

PMID- 15486757
TI  - Tamponade of presacral hemorrhage with hemostatic sponges fixed to the sacrum
      with endoscopic helical tackers: report of two cases.
AB  - Presacral venous hemorrhage is a severe complication in low rectal surgery. This
      complication was encountered in 5 of 165 patients (3 percent) who underwent a
      presacral dissection for rectal mobilization. Conventional hemostatic measures
      often are ineffective to arrest this hemorrhage, and a number of alternative
      hemostatic techniques have been proposed. We report the successful tamponade of
      presacral hemorrhage with absorbable hemostatic sponges fixed to the sacrum with
      endoscopic helical tackers.

PMID- 15486758
TI  - Surgisistrade mark mesh: a novel approach to repair of a recurrent rectovaginal
      fistula.
AB  - PURPOSE: This study was designed to repair a recurrent rectovaginal fistula using
      a new surgical approach that incorporates a Surgisistrade mark mesh. METHODS: A
      63-year-old female with a history of recurrent rectovaginal fistula, which was
      treated originally by a traditional mucosal advancement flap technique, underwent
      a surgical procedure in which a biocompatible mesh was incorporated into the
      repair. RESULTS: The patient was symptom-free one-year after the procedure.
      CONCLUSIONS: Surgery for recurrent rectovaginal fistula incorporating a
      Surgisistrade mark mesh can be used as an innovative option.

PMID- 15486760
TI  - LigaSure vs. diathermy hemorrhoidectomy.

PMID- 15486761
TI  - LigaSure for hemorrhoidectomy.

PMID- 15486764
TI  - Juvenile xanthogranuloma presenting with unilateral prominent nodule of the
      eyelid: report of a case and clinicopathological findings.
AB  - BACKGROUND: The purpose of this study is to report and describe the clinical and
      histopathologic findings in a patient with juvenile xanthogranuloma presenting as
      a relatively large, solitary, pedunculated mass on the left upper eyelid. CASE: A
      31-month-old Japanese girl presented with a pedunculated nodular lesion that had
      been developing since 4 months earlier. Otherwise, no abnormal findings were
      identified in either eye. In addition, no other abnormalities, including skin
      eruptions or nodules, were detected anywhere. The lesion was completely excised
      and examined histopathologically. OBSERVATIONS: Microscopic study revealed a
      histiocytic proliferation accompanied by lymphocytes and occasional plasma cells
      and eosinophils within the dermis. A moderate number of giant cells of the
      foreign-body and Touton types were present. In the immunohistochemical analysis,
      the proliferative histiocytes and giant cells showed positive immunoreactivity
      for vimentin and macrophage markers and negativity for S-100 protein. The
      diagnosis of juvenile xanthogranuloma was made. The findings of further detailed
      ophthalmologic and systemic examinations and evaluations were unremarkable.
      Therefore, the diagnosis was made of juvenile xanthogranuloma, solitary type,
      occurring on the eyelid. CONCLUSIONS: Although juvenile xanthogranuloma of the
      eyelid is uncommon and its occurrence anywhere in the eye is rare,
      ophthalmologists should be familiar with this entity. Juvenile xanthogranuloma
      should be included in the differential diagnosis of eyelid mass lesions.

PMID- 15486765
TI  - Effect of immunosuppression on survival of allograft limbal stem cells.
AB  - PURPOSE: To examine whether the application of immunosuppression enhances the
      survival of limbal allograft stem cells. METHODS: Wistar (allograft) or Fischer
      344 (isograft) rat limbal tissue was transplanted into superior lamellar excision
      sites in Fischer 344 rats. Allograft-recipient rats received an immunosuppressive
      agent or vehicle for 8 weeks. Graft-recipient rats were examined by slit-lamp
      microscopy for clinical signs of rejection, and some recipients were killed for
      immunohistochemical analysis during rejection. One month from the time of
      transplantation, other (five in each group) recipients received daily injections
      of 5-bromo-2-deoxyuridine (BrdU) at a dose of 5 mg/100 g for 2 weeks, followed by
      a 1-month BrdU-free period before death. After the rats were killed, limbal
      allograft eyes were removed for BrdU staining to identify label-retaining cells.
      The labeling index of transplanted limbal basal epithelial cells was determined.
      RESULTS: In nonimmunosuppressed allograft recipients, clinical rejection occurred
      between days 5 and 10 after transplantation (median, 7 days). In contrast,
      rejection was suppressed for more than 60 days (median value) when the
      immunosuppressive was administered. Numerous MHC class II(+), CD4(+), and CD8(+)
      T cells were identified with acute rejection. Immunosuppressive-treated
      allografts had significantly less inflammation compared with untreated controls.
      Furthermore, immunosuppressive-treated allografts showed more label-retaining
      basal cells in transplanted limbal epithelium compared with untreated allograft
      controls ( P < 0.01). CONCLUSIONS: The survival of limbal allograft stem cells
      can be improved by immunosuppression. The limbal allograft procedure described
      here provides a useful model for evaluating a suitable alternative means of
      sustaining the survival of corneal stem cells.

PMID- 15486766
TI  - Implantation of a keratoprosthesis of novel design in rabbits.
AB  - PURPOSE: To evaluate a keratoprosthesis, implanted by penetrating keratoplasty,
      in rabbits. METHODS: We implanted our keratoprosthesis (optics and flange
      portions of polymethylmethacrylate and a polyurethane skirt with micropores) into
      14 eyes of 14 rabbits. In four eyes, we evaluated histologically the junction
      between the keratoprosthesis and host cornea. Long-term keratoprosthesis survival
      was evaluated in ten eyes by slit-lamp biomicroscopy. RESULTS: The histological
      study showed good approximation of the keratoprosthesis to the host cornea in the
      junction area, with overlying superficial corneal stroma on the skirt, keratocyte
      and collagen fiber ingrowth into the micropores, and partial migration of
      epithelial cells onto the skirt. However, in the long-term survival study, eight
      out of ten eyes developed acute suture-related inflammation, considered to be
      from bacterial infection, requiring enucleation 30 +/- 18 weeks after
      implantation. The remaining two eyes have survived for 70 and 76 weeks.
      CONCLUSIONS: Our keratoprosthesis was well tolerated in the short term. However,
      further modifications are necessary to avoid corneal infection.

PMID- 15486767
TI  - Development and characterization of a rabbit corneal endothelial cell line.
AB  - PURPOSE: To develop a rabbit corneal endothelial cell line by transducing human
      papilloma virus (HPV) type 16 E6 and E7 oncogenes, and to characterize the
      inherent biological properties of the established cell line. METHODS: Primary
      rabbit corneal endothelial cells were infected with a recombinant retrovirus
      harboring HPV E6 and E7, and the transformed cells were clonally selected by
      G418. RESULTS: Among the total of eight independent clones, one cell line (Clone
      no. A3) cultured over 40 passages was chosen to further characterize its inherent
      biological properties. Typical cell doubling time for these cells was 51 h, and
      the mean cell density of a flask culture was 1140 cells/mm(2). The various genes
      that are important for corneal endothelial functions were expressed at a level
      comparable to that of their normal counterparts. Furthermore, Na(+)/K(+) ATPase
      activity was maintained throughout an extended period, and the measured value at
      passage 30 was about 10 nmol inorganic phosphate/mg protein per minute.
      CONCLUSIONS: These results suggest that the rabbit corneal endothelial cell lines
      obtained here maintain normal corneal endothelial characteristics, and could be
      used not only for biological studies on corneal endothelial cells but also for
      such applications as the reconstruction of the ocular surface with an artificial
      cornea.

PMID- 15486768
TI  - Quantitative analyses of mRNA and protein levels of neurotrophin-3 in the rat
      retina during postnatal development and aging.
AB  - PURPOSE: In this study, we sought to elucidate changes in the levels of
      neurotrophin-3 (NT-3) in the rat retina throughout postnatal development and
      aging. METHODS: We demonstrated NT-3 localization in the retina by
      immunohistochemistry. Protein and mRNA levels of NT-3 were quantified by enzyme
      linked immunosorbant assay and semiquantitative reverse transcriptase-polymerase
      chain reaction, respectively. NT-3 protein levels were assayed in the various
      regions of the central nervous system. Age-associated changes in protein and mRNA
      levels of NT-3 in the retinas were assessed. RESULTS: NT-3-immunoreactivity
      localized in the ganglion cell layer, inner nuclear layer, and outer nuclear
      layer. NT-3 content in the retina was relatively high in the examined regions of
      the central nervous system. Retinal NT-3 protein levels decreased after eye
      opening, whereas mRNA levels were constant. Both mRNA and protein levels of NT-3
      in the retinas of aged animals remained constant. CONCLUSIONS: Our observations
      suggest that NT-3 regulation in the retina is independent of increasing visual
      stimuli after eye opening. Stable expression of NT-3 in the adult retina suggests
      a possible role in the maintenance of the retinal environment throughout later
      life.

PMID- 15486769
TI  - Effects of topically instilled bunazosin hydrochloride and other ocular
      hypotensive drugs on endothelin-1-induced constriction in rabbit retinal
      arteries.
AB  - PURPOSE: To compare the inhibitory effect of topically instilled bunazosin
      hydrochloride (bunazosin), a selective alpha(1)-adrenoceptor antagonist, on the
      endothelin (ET)-1-induced vasoconstriction in rabbit retinal arteries with the
      effects of other ocular hypotensive drugs. METHODS: ET-1 was injected into the
      central part of the vitreous of both eyes of pigmented rabbits. Color fundus
      photographs were taken 5 min before and 60 min after the injection. The average
      diameters of the two major retinal arteries at the rim of the optic nerve head
      (ONH) were normalized with respect to ONH diameter. Fifty microliters of 0.01%
      bunazosin, or 0.12% isopropyl unoprostone (unoprostone), 1% dorzolamide
      hydrochloride (dorzolamide), 0.25% nipradilol, 0.5% betaxolol hydrochloride
      (betaxolol), or 0.5% timolol maleate (timolol) was instilled into one eye of each
      rabbit 60 min before the ET-1 injection. The series of experiments was performed
      as masked tests. RESULTS: Bunazosin and unoprostone inhibited the ET-1-induced
      constriction of retinal arteries by 103% (P = 0.012 versus contralateral eyes)
      and 50% (P = 0.037), respectively. Dorzolamide, nipradilol, betaxolol, and
      timolol had no significant effects in this experiment. CONCLUSIONS: Under our
      experimental conditions, bunazosin and unoprostone inhibited the ET-1-induced
      constriction. Hence, bunazosin and unoprostone may be clinically more effective
      against ET-1-related retinal diseases.

PMID- 15486770
TI  - Ocular findings of Beals syndrome.
AB  - BACKGROUND: In this report of two Okinawan patients with Beals syndrome and
      accompanying ocular complications, the symptoms of Beals syndrome and Marfan
      syndrome are compared. The etiology of these two syndromes is considered in
      relation to fibrillin. CASES: Case 1 was a 5-year-old boy who showed blue sclera
      and bilateral enlargement of optic disc cupping. Case 2 was a 24-year-old man who
      had partial coloboma of the lens, mild cataract, and bilateral glaucomatous disc
      cupping. OBSERVATIONS: Beals syndrome was diagnosed in these two patients based
      on the initial examination. In further investigations, while the patients were
      being observed without treatment, the intra ocular pressure of both patients
      remained within normal range. Funduscopy showed that the cup-to-disc ratio was
      0.8 bilaterally in both patients. Case 1 was followed up for 6 years with no
      changes. Ultrasound biomicroscopy examination in case 2 revealed hypoplasia of
      the ciliary body, leading to a diagnosis of glaucoma. This patient remains under
      observation. CONCLUSIONS: Two cases of Beals syndrome with ocular complications
      including glaucomatous optic disc cupping are reported. Ophthalmic examinations
      are recommended to identify the ocular complications of Beals syndrome. Further
      studies are needed to elucidate the relation between fibrillin abnormality and
      ocular complications in Beals syndrome.

PMID- 15486771
TI  - Acute asthma attack caused by ophthalmic application of antiallergic agents.
AB  - BACKGROUND: To investigate the induction of acute asthmatic attacks caused by
      several kinds of antiallergic eyedrops for the treatment of allergic conjunctival
      diseases in a patient with bronchial asthma and aspirin sensitivity. CASE: A 42
      year-old man with a 10-year history of bronchial asthma and with aspirin
      sensitivity, who had been given disodium cromoglycate (DSCG) to be applied
      topically, developed asthma after applying DSCG drops. OBSERVATIONS: After the
      instillation of DSCG, tranilast, ibudilast, and ketotifen, the peak expiratory
      flow rate (PEFR) decreased in this patient and asthmatic signs developed.
      However, there was no decrease in the PEFR after challenge with pemirolast,
      levocabastine, or fluorometholone (0.1%) eyedrops, or saline as control.
      CONCLUSIONS: This case suggests that mast-cell-stabilizer eyedrops might induce
      an asthma attack in patients with a history of asthma and aspirin or nonsteroidal
      antiinflammatory drug allergy. Mast-cell-stabilizing eyedrops should be
      prescribed for such patients with special precautions unless the patient is known
      to tolerate mast cell stabilizers without difficulty.

PMID- 15486772
TI  - Prefoveolar membrane in macular hole opercula formation.
AB  - PURPOSE: To better understand the process of macular hole opercula formation by
      both optical coherence tomography and intraoperative observations. METHODS:
      Seventy-nine eyes of 71 consecutive patients with stages 1 to 3 idiopathic
      macular holes were studied using optical coherence tomography (OCT). In eyes with
      stage 1 or 2 holes undergoing vitrectomy, meticulous observation of the posterior
      hyaloid and the macular hole was carried out before and after peeling of the
      posterior hyaloid. RESULTS: In 6 of 12 eyes with stage 1 holes, OCT showed tiny
      steps on the anterior wall of the foveal cyst, connecting to the detached
      posterior hyaloid face. In eyes with stage 2 holes, opercula were incompletely
      detached and connected to the hole edge. In eyes with stage 1 holes that were
      operated on, a small semitransparent opacity was noted at the posterior hyaloid
      face after peeling of the posterior hyaloid in the absence of defects of the
      anterior wall of the cyst. In 10 of 12 eyes with stage 2 holes undergoing
      vitrectomy, the size of the foveal opening remained unchanged after peeling of
      the posterior hyaloid, and a semitransparent opacity was observed at the detached
      hyaloid face. All opercula in stage 3 holes that were clearly imaged by OCT were
      positioned above the plane of the posterior hyaloid face. CONCLUSIONS: These
      findings suggest that the anterior wall of an evolving macular hole is composed
      of two layers: a prefoveolar membrane and the inner retinal layer. The
      prefoveolar membrane may play an important role in both persistent vitreofoveal
      adhesion and macular hole opercula formation.

PMID- 15486773
TI  - High prevalence of myopia in Japanese patients with multiple evanescent white dot
      syndrome.
AB  - PURPOSE: To compare the incidence of refractive errors in Japanese patients with
      multiple evanescent white dot syndrome (MEWDS) with that in age- and sex-matched
      controls. METHODS: Fifty Japanese patients with MEWDS (11 males and 39 females;
      ages, 15-58; mean 29.9 years) were studied retrospectively. The refractive errors
      (spherical equivalent) in the patients were compared with those of 150 age- and
      sex-matched controls. RESULTS: The mean refractive error in the patient group was
      -5.30 +/- 4.58 diopters (D) which was significantly greater than that in the
      controls (-2.57 +/- 2.94 D, P = 0.0005). Twenty-two (44.0%) of the 50 MEWDS
      patients had refractive errors >-6.00 D; whereas 14 (9.3%) of 150 normal subjects
      had this degree of myopia. This difference was statistically significant ( P <
      0.005). CONCLUSION: Japanese patients with MEWDS tend to be highly myopic.

PMID- 15486774
TI  - Visual outcome in central retinal and branch retinal artery occlusion.
AB  - PURPOSE: To study retrospectively the presenting visual acuity and the visual
      outcome in patients with central retinal artery occlusion (CRAO) and in patients
      with branch retinal artery occlusion (BRAO). METHODS: We studied the visual
      acuity and outcome in 23 patients (23 eyes) with CRAO and in 30 patients (30
      eyes) with BRAO that met the inclusion criteria: a funduscopic appearance of
      retinal whitening, a delay in arterial dye filling in a fluorescein angiogram,
      the first examination in our hospital within 7 days of onset, and a minimum
      follow-up period of 90 days. RESULTS: Both presenting acuity and final acuity
      were far worse in patients with CRAO than in patients with BRAO. A final acuity
      worse than 0.1 was observed in 14 of the 23 (61%) patients with CRAO and in only
      1 of the 30 (3%) patients with BRAO. Only 5 of the 23 (22%) patients with CRAO
      and 24 of the 30 (80%) patients with BRAO showed a final acuity of 0.5 or better.
      CONCLUSION: Visual acuity in patients with CRAO is poor at presentation, and the
      prognosis is generally poor, with a few exceptions. In contrast, the visual
      acuity in patients with BRAO is far better both at presentation and at the final
      visit.

PMID- 15486775
TI  - The medial canthal tendon is composed of anterior and posterior lobes in Japanese
      eyes and fixes the eyelid complementarily with Horner's muscle.
AB  - PURPOSE: To report that the medial canthal tendon (MCT) is not simply the
      aggregate of the orbicularis oculi muscle (OOM) and its tendon. METHODS: Twenty
      eyelids of 10 cadavers were used. The cadavers, seven male and three female, were
      all Japanese, with an average age of death of 76.2 years. The relationship
      between the MCT and the OOM, and between the tarsus and Horner's muscle were
      investigated. Histological findings were obtained with hematoxylin and eosin
      staining. RESULTS: The MCT was structured with an anterior lobe, the tendon from
      the tarsal area of the OOM, and a posterior lobe, the muscle-tendon transition
      area in the orbital area of the OOM. The nasal aspect of the tarsus was fixed by
      Horner's muscle. CONCLUSIONS: The MCT and Horner's muscle are located in an
      important area of the eyelid; therefore, it is essential to understand their
      precise anatomy.

PMID- 15486776
TI  - Conjunctival inverted follicular keratosis: a case report.
AB  - BACKGROUND: We report a case of inverted follicular keratosis (IFK) on the
      conjunctiva. A few cases of IFK have been reported in the literature, but it
      appears that IFK on the conjunctiva has never been reported. CASE: A 21-year-old
      man was referred for evaluation of a conjunctival mass. OBSERVATIONS: By slit
      lamp biomicroscopy, an 8 x 5 x 3 mm mass was observed over the nasal conjunctiva
      adjacent to the limbus in the left eye. An excisional biopsy of the lesion was
      carried out. The results of a pathologic examination showed IFK. During the 9
      month follow-up period, the patient had no recurrence of the lesion. CONCLUSION:
      IFK can be considered in the differential diagnosis of conjunctival masses as a
      rare specific lesion.

PMID- 15486777
TI  - Effects of oral Ginkgo biloba supplementation on cataract formation and oxidative
      stress occurring in lenses of rats exposed to total cranium radiotherapy.
AB  - PURPOSE: To determine the antioxidant role of Ginkgo biloba (GB) in preventing
      radiation-induced cataracts in the lens after total-cranium irradiation of rats
      with a single radiation dose of 5 Gy. METHODS: Sprague-Dawley rats were randomly
      divided into three groups. Group 1 received neither GB nor irradiation (control
      group). Group 2 was exposed to total-cranium irradiation of 5 Gy in a single dose
      [radiation therapy (RT) Group], and group 3 received total cranium irradiation
      from a cobalt-60 teletherapy unit, plus 40 mg/kg per day GB (RT+GB group). At the
      end of the tenth day, the rats were killed and their eyes were enucleated to
      measure the antioxidant enzymes, the activities of superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px), and the lipid peroxidation level
      [malondialdehyde (MDA)]. RESULTS: Irradiation significantly increased both the
      MDA level and the activity of GSH-Px, and significantly decreased the activity of
      SOD in the rat lenses. GB supplementation significantly increased the activities
      of SOD and GSH-Px enzymes and significantly decreased the MDA level. Total
      cranium irradiation of 5 Gy in a single dose promoted cataract formation, and GB
      supplementation protected the lenses from radiation-induced cataracts.
      CONCLUSIONS: We suggest that Ginkgo biloba is an antioxidant that protects the
      rat lens from radiation-induced cataracts.

PMID- 15486778
TI  - Systemic malignant lymphoma 17 years after bilateral orbital pseudotumor.
AB  - PURPOSE: To report a patient who developed systemic malignant lymphoma 17 years
      after bilateral orbital pseudotumor. CASE. A 24-year-old man developed bilateral
      orbital pseudotumor. He was stable until 17 years later, when he was afflicted
      with systemic malignant lymphoma, a diffuse large B-cell lymphoma, and he died of
      the disease. He showed no new orbital lesion at the presentation of systemic
      lymphoma. Pathological diagnosis at autopsy was systemic malignant lymphoma with
      bilateral orbital pseudotumor. METHODS: Immunohistochemical reexamination of the
      paraffin-embedded tissue and polymerase chain reaction of paraffin sections.
      RESULTS: Histopathologically, the orbital masses resected on different occasions
      consisted of small lymphocytes and plasma cells. Immunohistochemical staining
      revealed an immunoglobulin light chain kappa and lambda bitype of B-cell
      lymphocytes and plasma cells. In contrast, the cervical lymph node showed large
      lymphoma cells that were positive only for lambda light chain, indicative of a
      lambda monotype. Amplification by polymerase chain reaction of the immunoglobulin
      heavy chain gene from paraffin sections demonstrated clonal rearrangement in the
      cervical lymph node but showed no clonality in the orbital tumor, supporting
      altogether the diagnosis of orbital pseudotumor. CONCLUSION: Orbital pseudotumor
      should be carefully followed for possible development of systemic malignant
      lymphoma.

PMID- 15486779
TI  - Scanning laser polarimetry measurement with variable corneal compensation
      compared with fixed corneal compensation.

PMID- 15486780
TI  - Pseudodacryocystitis: a complication related to a Lester-Jones tube.

PMID- 15486783
TI  - [Stretching esophagopexy on the gastric wall is the best treatment for
      gastroesophageal reflux disease].

PMID- 15486784
TI  - [Preoperative chemoradiation in esophageal cancer: experience of a single center
      in 102 patients].
AB  - The (dis-)advantages of preoperative chemoradiation in patients with esophageal
      cancer (EC) are still controversial as data are lacking showing a clear cut
      benefit. Therefore, data of neoadjuvant therapy of our hospital have been
      analyzed. Since 1994 102 patients with an EC (33 % adenocarcinoma, 67 % squamous
      cell cancer, scc) were operated after receiving preoperative chemoradiation (36
      Gy radiation, 1.8 Gy/day for 4 weeks, 500 mg/m (2) 5-FU for 4 weeks and 20 mg/m
      (2) Cisplatin, day 1-5, week 1 and 4). Operation was performed usually 8-10 weeks
      after treatment start. In 11.7 % of patients with an adenocarcinoma a complete
      pathological response (CR, pT0N0M0) was observed and a pT0 stage in 20.6 %. 38.2
      % of these patients were staged as pN0. Postoperative morbidity was observed in
      66 % (anastomotic leakage in 20 %, recurrent nerve palsy in 23 %). In-hospital
      mortality was 5.9 %. 5-year survival was calculated as 30.5 %, in patients wit a
      CR 66 %.26.5 % of patients with a scc revealed a CR. However no effect at all was
      observed in 32 % of these patients. 56 % were staged as pN0. Postoperative
      morbidity was observed in 87 % (anastomotic leakage in 16 %, recurrent nerve
      palsy in 32 %). In-hospital mortality was 11.8 %. 5-year survival was calculated
      as 19.2 %, in patients with a CR 45 %. The impact of pN stage was significant (p
      = 0.0052). These results underline the benefit of neoadjuvant therapy in patients
      with a CR. Further on, a pN0 stage is an important prognostic indicator. However,
      it remains open, whether neoadjuvant therapy leads to a downstaging of lymph node
      involvement, as histological confirmation in clinically positive lymph node is
      seldom performed prospectively.

PMID- 15486785
TI  - [Molecular aetiology of nodular goitre -- consequences for therapy?].
AB  - Up to 15 % of the adult German population display an enlarged thyroid gland and
      up to 30 % present thyroid nodules. Iodine deficiency is the most important
      factor in the etiology of nodular goiter. Insulin-like growth factor-I is
      overexpressed in thyroids in severely iodine deficient areas. There is evidence
      that iodolactones are mediators of thyroid hormone autoregulation. However
      familial and twin studies demonstrated a genetic component in the etiology of
      nodular goiter. Linkage analysis identified two chromosomal regions (MNG-1, Xp
      22) in multinodular goiter. Other possible candidate genes or markers such as TG,
      TPO, NIS, PDS and TSH-R were not identified. Nodular goiter certainly comprises a
      number of genotypes. TSH receptor mutations result in activation of the cAMP
      cascade. Cells with a constitutively activated cAMP cascade have an increased
      growth advantage due to their TSH independent cAMP stimulation. Alimentary iodine
      supply should be the first choice in primary prevention of nodular thyroid
      disease in iodine deficient areas, because prevalence of nodular goiter is
      negative correlated with individual iodine status in epidemiological surveys.
      Surgical removal of nodular goiters should include nearly the hold thyroid tissue
      to avoid recurrent goiter.

PMID- 15486786
TI  - [Titanised polypropylene meshes: first clinical experience with the implantation
      in TAPP technique and the results of a survey in 22 German surgical departments].
AB  - Titanised polypropylene meshes for the treatment of inguinal hernias are
      available since 2001. The reduced weight of the mesh, the increased size of the
      net meshes amounting to 1 mm, and the titan surface are supposed to improve the
      tissue compatibility and lower the risk of post implant mesh dislocation. AIM: It
      was the aim of the study to examine the characteristics of the mesh concerning
      the feasability for implantation in TAPP technique as well as the tolerability of
      titanised polypropylene meshes under short term observation. PATIENTS AND
      METHODS: 80 titanised polypropylene meshes were implanted in TAPP technique into
      patients with inguinal hernias. The operation, the clinical course and
      complications were prospectively documented including a median follow up of 2
      months.A survey of 22 German surgical departments was carried out. In a period of
      8.3 months each institution gained experience with a median of 83 titanised
      polypropylene meshes in the treatment of inguinal hernias. The characteristics of
      the departments, certain aspects of implantation technique and reported
      complications were evaluated. RESULTS: The median operation time amounted to 52
      minutes. In 5 patients umbilical hernias were simultaneously repaired. In our own
      series in 2/3 (rd) of the cases the 35 g/m (2) and in 1/3 (rd) of the cases the
      16 g/m (2) version of the mesh was used. 17 % of the meshes in our series were
      not fixed with staples. Only minor reversible complications occurred in our
      patient group. Mesh related major complications were observed neither in our
      patients nor in the patients of the departments we surveyed. None of our patients
      required analgesic medication. Postoperatively 89 % of the patients were highly
      satisfied with the operation. The heavier version of the mesh was used more often
      by surgeons of the other departments. Only in 3 departments both versions of the
      mesh were used regularly. The trend to use less or no staples at all could also
      be observed at the other departments. CONCLUSION: The implantation of the
      titanised polypropylene meshes for the repair of inguinal hernia in TAPP
      technique is feasable. The intraoperative handling and the early clinical results
      are good. There were no major or mesh related complications or incompatibilities.
      Whether the rate of recurrence is comparable to conventional meshes and whether
      chronic pain syndromes can be reduced must be evaluated in long-term studies.

PMID- 15486787
TI  - [Laparoscopic hernioplasty by transabdominal preperitoneal approach].
AB  - INTRODUCTION: Despite the increasing acceptance of the TAPP-procedure by patients
      and general practitioners this method has to be further examined. In addition to
      the classic surgical criteria of examination, subjective aspects of patient
      comfort must be taken into consideration as they are getting more and more
      significant for the evaluation of different methods. METHODS: According to this
      objective patients were clinically examined and questioned about specific topics
      of quality of life after TAPP-operations. Furthermore, the patients documentation
      (medical report/OP-report) was evaluated retrospectively. RESULTS: Between1995
      and 1998 endoscopic transabdominal preperitoneal hernioplasty was used for 267
      inguinal hernia repairs in 204 patients. 155 patients could be interviewed about
      the operative outcome and 199 operated inguinal hernias could be examined
      physically and sonographically. The recurrence rate was 2.5 %, the rate of major
      complications was 4.4 %. Postoperative pain-syndrome were found as a major
      complication in only two cases (1.3 %), postoperative nervous disorders could be
      diagnosed in 3.5 % of the patients. Further subjective complaints were seen in 19
      % of the patients. The median postoperative period until the resumption of sexual
      intimacy was approximately two weeks, but six male patients reported about long
      lasting pain in copulation (3.9 %). DISCUSSION: With regard to the aspects
      mentioned above, the TAPP-procedure provided exellent results in the examined
      patient cohort and therefore turned out to be at least comparable with
      competitive methods. Nevertheless, the postoperative pain in sexual activity that
      a few male patients complained of represents a new aspect which has to be further
      investigated.

PMID- 15486788
TI  - [Long-term results for Heller-myotomy with anterior semifundoplication in
      achalasia].
AB  - INTRODUCTION: The positive success rate of cardiomyotomy in the treatment of
      achalasia has recently - especially in young patients - resulted in a primary
      operative treatment concept. Few studies of long-term effects of myotomy
      concerning the removal of dysphagia and the development of gastroesophageal
      reflux have been submitted. PATIENTS AND METHODS: In the period between September
      1985 and March 2003, an open, transabdominal Heller-myotomy combined with a Dor
      semifundoplication was carried out in 93 patients with achalasia. 77 patients
      were followed for more than 6 months postoperatively (median follow-up: 70
      months). The procedure was prospectively observed, and patients were questioned
      concerning their clinical symptoms by means of structured interviews. X-ray
      examinations of the esophagus were pre- and postoperatively available of 47
      patients, manometrical findings before and after myotomy of 26 patients. RESULTS:
      The pre-operatively existing symptoms dysphagia, regurgitation, retrosternal pain
      and weight-loss could be improved by myotomy in 97 % of the patients with good to
      excellent long-term results. Post-operatively, a significant reduction of the
      median maximum diameter of the esophagus of 50 mm to 30 mm was evident (p <
      0.001), whereas the diameter of the cardia increased from 3 mm to 10 mm (p <
      0.001). The pre-operative resting pressure of the lower esophageal sphincter
      (LES) of 29.3 mmHg was reduced to 7.9 mmHg (p < 0.001). Patients suffering from
      reflux esophagitis showed a significant lower resting pressure of the LES (4
      mmHg) in comparison with patients without reflux esophagitis (8.5 mmHg) after
      myotomy (p=0.045). The clinical long-term results of patients with preceding
      pneumatic dilation did not differ significantly from those with primary myotomy.
      CONCLUSION: Conventional Heller-myotomy with anterior semifundoplication can in
      the long run remove the symptoms existent in achalasia with high efficiency. If
      the decrease of the post-operative resting pressure of the LES is too intense (<
      5 mmHg), a possible gastroesophageal reflux has to be taken into account. The
      results of open cardiomyotomy have to be regarded as standard for assessing the
      minimal-invasive procedure.

PMID- 15486789
TI  - [Laparoscopic heller cardiomyotomy either combined with a Dor or Toupet procedure
      in the treatment of achalasia].
AB  - INTRODUCTION: The treatment of achalasia has undergone a dramatic evolution over
      the past ten years with the introduction of advanced laparoscopic techniques
      beside the use of balloon dilatation and injections of botulinumtoxin. With the
      introduction of the laparoscopic Heller cardiomyotomy the question was raised
      again whether and if so which antireflux measures are meaningful in combination
      with the cardiomyotomy. PATIENTS AND METHOD: Since 1998, 51 patients underwent
      laparoscopic cardiomyotomy in the surgical department of the Marienhospital
      Herne, Ruhr University Bochum. To prevent postoperative gastroesophageal reflux
      we performed a Dor fundoplication in 13 patients and a Toupet fundoplication in
      38 patients. The mean period of observations was 17 months (3-45 months). All
      patients were evaluated through a symptoms score. 16 patients could be clinically
      and objectively followed-up. RESULTS: The mean operation time was 170 min. (80
      290 min). The intraoperative complications were 8 mucosal disruptions without
      further morbidity and 1 pneumothorax. Postoperative complications were 1 scarring
      restenosis and 1 wrap dislocation. Improvement of symptoms was reported in 94.2 %
      of patients with good or excellent results. In 5.8 % of patients symptoms of
      reflux were claimed. There was no significant difference in results between Dor-
      and Toupet-fundoplication. CONCLUSION: Laparoscopic Heller cardiomyotomy with
      either a Dor or Toupet fundoplication are equivalent with respect to short- and
      middle-term outcome and efficient procedures with low rate of morbidity and
      mortality in the treatment of achalasia. A long-term observation period is
      necessary for determining which type of fundoplication has to be performed
      particularly regarding restenosis and reflux rate.

PMID- 15486790
TI  - [Laparoscopic splenectomy: first experiences with a 3-trocar-technique and the
      'hanging-spleen-maneuver'].
AB  - AIMS: Laparoscopic splenectomy has been established as standard procedure for
      elective splenectomy and is performed for a variety of haematological diseases.
      However, different techniques have been used and a four- to five trocar technique
      is applied in most instances. We report our experience with a three-trocar
      technique using the triangular liver retractor and the so-called "hanging spleen"
      maneuver. METHODS: Data were obtained from a prospectively collected computer
      database of all patients who underwent elective laparoscopic splenectomy between
      April 2001 and July 2003. RESULTS: The study population consisted of 26 patients
      (14 men, 12 women, mean age: 45 years; range: 16-75 years). Median operative time
      was 140 min (85-310 min). There was one conversion (3.8 %) due to a suspected
      malignancy, which was finally not confirmed. A fourth trocar had to be placed in
      two cases (10 %) due to a large left lobe of the liver. In two patients a small
      midline incision was made to extract the spleen in toto for pathohistological
      examination due to a splenic metastasis. In the remaining cases the spleen was
      morcellated in an endobag. Accessory spleens were found in 1 patient (3.8 %).
      There were two bleedings following operation, which required laparotomy in one
      patient. There were no deaths (0 %). The median postoperative hospital stay was 7
      days (range 3-17). CONCLUSIONS: Laparoscopic splenectomy can be performed safely
      in the vast majority of patients. The described technique using three trocars
      with the so-called "hanging spleen" maneuver can be used in about 90 % of cases.

PMID- 15486791
TI  - [Transumbilical laparoscopic-assisted "one-trocar" appendectomy -- TULAA -- as an
      alternative operation method in the treatment of appendicitis].
AB  - INTRODUCTION: Appendectomy is one of the most commonly performed surgical
      procedures in general surgery and laparoscopic appendectomy represents the
      beginning of minimal invasive era in visceral surgery. But until yet,
      laparoscopic appendectomy is not the standard method for removal of the appendix
      and the discussion about the value and the advantages of laparoscopic
      appendectomy is still going on between the opponents and advocates of this
      method. In this article we present the transumbilical laparoscopic assisted "one
      trocar" appendectomy (TULAA) as an alternative procedure for appendectomy and our
      experiences with this technique, which is up to now not very well known in
      Germany. METHOD: From November 1, 2000 to December 31, 2002, we performed
      appendectomy in 350 patients. 163 patients (46.6 %) underwent TULAA in the
      technique of Begin. All of them were examined two weeks and three months after
      surgery. RESULTS: In 94.5 % the "one-trocar" appendectomy was successful and
      there were no intraoperative complications. The mortality was 0 %. Conversion to
      the open procedure was necessary in 3 patients (1.8 %), respectively introduction
      of accessory trocars was necessary in 6 patients (3.7 %). In 111 from 163
      patients (68.1 %) appendectomy was performed because of acute appendicitis. In
      14.1 % we detected additional secondary findings during the laparoscopy. The
      postoperative complication rate was 3.6 %. CONCLUSION: The transumbilical
      laparoscopic assisted "one-trocar" appendectomy complements the minimal invasive
      procedures in visceral surgery. The operating technique combines the simplicity
      and the safety of conventional appendectomy with the survey of laparoscopic
      appendectomy. It minimizes the trauma of surgery and shows a perfect cosmetic
      result.

PMID- 15486792
TI  - [Laparoscopic therapy of appendicovesical fistula -- two case reports].
AB  - Two cases of appendicovesical fistula are reported. One case was caused by
      Crohn's disease, the second case by a chronical appendicitis. The guiding
      symptoms in both cases were coprosuria and pneumaturia, with chronical infection
      of the urinary tract. No diagnostic imaging method was able to detect the
      fistula. The correct diagnosis was finally made by laparoscopy followed by
      laparoscopical appendicectomy and fistula closure. The clinical symptoms alone
      seem to be sufficient for indication to operate. Thus, an early laparoscopic
      operation significantly can shorten the length of disease.

PMID- 15486793
TI  - [Importance of endorectal 3-D-ultrasonography in diagnosis of rectum cancer].
AB  - BACKGROUND: Preoperative staging of rectal tumors is considered essential to
      tailor treatment for individual patients. The aim of the present study was to
      evaluate the accuracy of endorectal ultrasonography in preoperative staging of
      rectal cancer. METHODS: 357 patients with rectal adenocarcinoma underwent
      endorectal ultrasonography evaluation during an eight year period. The evaluation
      was performed by four surgeons. We compared the endorectal ultrasonography
      staging with the pathology findings. Patients with preoperative chemoradiation
      were excluded from the study. RESULTS: Overall accuracy in assessing the level of
      rectal wall invasion was 77.3 %, with 9.3 % of the tumors overstaged and 8.1 %
      understaged. Accuracy in assessing nodal involvement in 313 patients treated with
      radical surgery was 74.9 %, with 8.9 % overstaged and 8.9 % understaged.
      CONCLUSION: The accuracy of endorectal ultrasonography in assessing the deepth of
      tumor invasion is good, but lower than previosly reported. The technique is
      precise in distinguishing between benign tumors and invasive cancer. The results
      depend on the experience of the surgeon.

PMID- 15486794
TI  - [Usefulness of anal endosonography in the assessment of fistula-in-ano].
AB  - AIM: The purpose of the present study was to define the diagnostic value of anal
      endosonography in the diagnostic work-up of fistula-in-ano. METHODS: A
      retrospective study was carried out on 191 consecutive patients (m: 121; f: 70;
      mean age: 44.0 +/- 12.5 years; range: 0.5-77 years) who were diagnosed to suffer
      from fistula-in-ano by performing anal endosonography in an outpatient setting.
      All images were obtained with a Combison 310A ultrasound scanner (Kretz GmbH,
      Zipf, Osterreich) and 5-Mhz and 7.5-MHz transducer. 131 patients underwent
      surgery. According to the endosonographic findings fistulas were classified as
      transsphincteric in 44 %, intersphincteric in 22 %, subanodermal in 16 %,
      anovaginal in 8 %, suprasphincteric in 5 %, extrasphincteric in 1 % and others in
      4 %. RESULTS: In 125 patients (95 %) the preoperative diagnosis was confirmed
      intraoperatively. This cohort included 12 patients with a complex fistula system.
      In only 6 patients the preoperative ultrasound finding was misinterpreted.
      CONCLUSION: In conclusion this study has shown that anal endosonography is a
      useful and reliable tool in the preoperative evaluation of uncomplicated and
      complicated anorectal fistulas.

PMID- 15486795
TI  - [Variations of superficial nerves at the pelvis considering orthopaedic surgical
      approaches].
AB  - PROBLEM: Intraoperative injuries of vessels and nerves are common risks and
      repeatedly described in orthopaedic pelvic surgery. Especially in pelvic
      osteotomies or bone harvesting procedures subcutaneous nerves are at risk for
      damage. In this study we elucidated the variations of subcutaneous nerves by
      anatomic preparation exposure with regard to the anterior and posterior spines.
      METHODS: To investigate the different anatomic variations the iliohypogastrical,
      lateral cutaneous, subcostal and the cluneal nerves of 10 human cadavers were
      prepared and exposed bilaterally at the anterior, lateral and posterior pelvic
      region. For determination of anatomically important reference points the distance
      of these structures to the anterior superior spine was measured and compared with
      present datas in literature with respect to the ilioinguinal (Letournel) and
      iliofemoral (Smith- Petersen) approach. RESULTS: We found a high variability of
      superficial pelvic nerves. Our findings differ somehow with datas of recent
      papers. CONCLUSION: The findings of our study stress the importance of basic
      knowledge and thorough preparation in surgical procedures at the pelvis including
      harvesting bone grafts to minimize donor site morbidity.

PMID- 15486796
TI  - [Efficiency of low-intensity pulsed ultrasound on distraction osteogenesis in
      case of delayed callotasis -- clinical results].
AB  - AIM: Low-intensity pulsed ultrasound has been proven to accelerate fracture
      healing both clinically and experimentally. In this study the influence of low
      intensity pulsed ultrasound during distraction-osteogenesis in case of delayed
      callotasis was investigated. METHOD: 20 patients could be included in this study.
      16 patients initially were treated because of fractures of the lower leg, 2
      because of fractures of the femur with resulting shortening of the afflicted
      limb. One patient suffered from chronic osteitis at the thigh and one from
      chronic osteitis at the upper arm without previous trauma. Because of delayed
      callotasis an adjunctive ultrasound treatment device was transcutaneously applied
      (frequency 1.5 MHz, signal burst width 200 microseconds, signal repetition
      frequency 1.0 kHz, intensity 30 mW/cm (2)) with the transducer placed at the
      distraction zone for 20 minutes daily. In all cases in-home treatment was
      performed. Evaluation was done by radiographic and sonographic controls of the
      distraction zone during examination of all patients at the outpatients'
      department every 3-4 weeks. RESULTS: Progress of callotasis was achieved in 15
      out of 20 patients. Patients who were smokers during ultrasound therapy showed
      lower healing rates than those who never smoked. 2 patients suffering from
      osteitis of the tibia and missing callotasis had to be amputated. 3 other
      patients needed additional operative treatment including cancellous bone grafts
      because of missing new bone formation. Negative effects of low-intensity pulsed
      ultrasound during therapy could not be detected. CONCLUSION: We conclude that
      ultrasound treatment can accelerate bone maturation and formation in distraction
      osteogenesis, sometimes even in states of poor callotasis. It may provide a
      method of great promise in cases where delayed bone formation during distraction
      osteogenesis occurs.

PMID- 15486797
TI  - [Femoral nerve palsy due to excessive granuloma in aseptic cup loosening in
      cementless total hip arthroplasty].
AB  - AIM: Femoral nerve palsy after total hip arthroplasty can result from several
      causes. Delayed neuropathies of the femoral nerve because of excessive granuloma
      in loosened implants are a rare condition. CASE REPORT: We report the case of
      delayed neuropathy of the femoral nerve after cementless total hip arthroplasty
      because of aseptic loosening of the cup. Electrophysiologic evaluation revealed a
      severe lesion of the femoral nerve with sensomotoric deficits. An abdominopelvic
      computed tomography (CT) scan revealed an excessive granuloma with a large
      intrapelvic portion. After revision of the loosened acetabular component and the
      femoral nerve and removal of the granuloma the neurologic symptoms improved.
      CONCLUSION: Regular (1-2 years) clinical and radiological follow-ups are
      requested after total hip arthroplasty to prevent excessive loosening of
      implants, excessive granuloma and severe sequelae like nerve damage.

PMID- 15486798
TI  - [Recurrent micro-satellite stable colonic cancer: prolonged survival of 16 years
      without adjuvant therapy].
AB  - Long-term survival in malignant disease is often linked to intensified
      therapeutic interventions. We report the case of a colonic cancer in a 78 years
      old female patient, who underwent her first operation in 1987 for a symptomatic
      T4 carcinoma. Since then, the patient has always denied any form of follow-up
      examination and adjuvant therapy. Recently, she has undergone her fourth
      operation, which for the first time demonstrated peritoneal carcinosis, and is
      still in very good health.Clinical experience shows that in some cases standard
      therapies may unexpectedly produce extremely long survival times. This has to be
      kept in mind when the value of prognostic markers is discussed and limits the
      validity of survival data in the context of small scale studies dealing with
      especially extended therapeutic protocols.

PMID- 15486799
TI  - [Prof. Dr. med. Dr. h. c. Jochen Schulte am Esch: A Visionary of Our Specialty
      Celebrates his 65th Birthday].

PMID- 15486800
TI  - [The Turco-German relations in anaesthesiology].

PMID- 15486801
TI  - [Risks posed by venomous animals -- accidents due to snakebite envenomation].
AB  - In regions where poisonous animals are widely distributed, the management of
      injuries due to these animals is part of the routine medical care. Personnel e.
      g. deployed for humanitarian aid missions in these areas have to be prepared to
      face these challenges as well. Beside this group zoo personnel and snake charmers
      here in Europe are also endangered. The most common form of animal poisoning is
      due to snake bites. There are approximately 600 different species of poisonous
      snakes, commonly found in the warm climatic regions. But poisoning from spiders,
      scorpions and some marine animals can also be life threatening. There are
      different kinds of snake venoms, which result into different clinical
      presentations depending on the components of the venom. The venom may be
      cytotoxic, hematotoxic, neurotoxic, rhabdomyolytic, cardiotoxic, renotoxic or may
      cause an autoimmune reaction by complement activation. In the management of
      injuries following animal poisoning, besides the first aid measures taken, the
      injured is supposed to be managed according to the poison component in the venom
      with specific antivenin treatment and supportive therapeutic care. There are mono
      and polyvalent antivenins available. Noneffective first-aid measures or measures
      which can cause further trauma must always be avoided. In general adapted
      behaviour in the field can prevent envenomation. Education on preventive measures
      with the aim of behaviour change are central components for pre-deployment
      preparations.

PMID- 15486802
TI  - Sedation for fiberoptic bronchoscopy: fewer adverse cardiovascular effects with
      propofol than with midazolam.
AB  - OBJECTIVE: To study the influence of the sedatives propofol and midazolam on
      cardiovascular parameters in patients undergoing fiberoptic bronchoscopy (FOB).
      METHODS: 100 patients without a history of cardiac disease undergoing diagnostic
      FOB were investigated in a prospective-randomized design. After premedication
      with intramuscular atropine (0.01 mg/kg BW) patients received sedation with
      either propofol (group P, n = 50) or midazolam (group M, n = 50). Heart rate,
      arterial oxygen saturation (psaO (2)) and non-invasive blood pressure were
      recorded prior to and immediately after induction of sedation, when at the level
      of vocal cords, during the interventional diagnostic procedure (IDP) and 15 min
      after the end of the FOB. RESULTS: The mean heart rate and systolic pressure were
      significantly lower in group P when compared with group M when at the level of
      vocal cords and during the IDP (p < 0.05). The total incidence of major
      arrhythmias was 10 % and the incidence of minor arrhythmias was 62 %. A decline
      in psaO (2) < 90 % occurred in 16 patients of group M and 5 patients of group P
      (p = 0.44). CONCLUSION: Propofol, when used as a sedative for FOB, is associated
      with lower hemodynamic side effects than in patients undergoing FOB with
      midazolam. In addition, it is well-tolerated by patients with pre-existing
      pulmonary disease. Even patients without a history of heart disease should be
      monitored for cardiac arrhythmia while undergoing FOB for pulmonary disease,
      especially patients with a FEV (1) of less than 50 % of the predicted value.

PMID- 15486803
TI  - [Catecholamine levels in plasma and cerebrospinal fluid of neurosurgical patients
      with normal and elevated intracranial pressure].
AB  - OBJECTIVE: Catecholamine levels in the plasma and cerebrospinal fluid of 21
      neurosurgical patients with hydrocephalus and with normal and elevated
      intracranial pressure were determined prospectively in a clinical study. METHODS:
      The study comprised 11 patients with normal intracranial pressure (8 female, 3
      male, group 1) and 10 patients with elevated intracranial pressure (6 female, 4
      male, group 2). The patients underwent a ventriculo-peritoneal shunt operation,
      external ventricular drainage or ventriculocisternostomy. The measuring times
      were set as follows: time 1: pre-operative; time 2: intra-operative; time 3: post
      operative. The anaesthetic for the operations was administered as a total
      intravenous anaesthesia with propofol and alfentanil, muscle relaxation being
      achieved with rocuronium bromide or cis-atracurium. RESULTS: Measurements of the
      catecholamine levels (adrenaline, noradrenaline and dopamine) at the three set
      times revealed an intra-operative fall compared to the initial pre-operative
      value and a rise in the catecholamine level again after the operation. It is
      likely that this largely reflects the course of the anaesthetic. The fall in the
      plasma catecholamine level was much slighter in group with elevated intracranial
      pressure. But in the group of patients with elevated intracranial pressure the
      catecholamine levels found in the plasma were much higher than those of the
      patients without elevated pressure. In the case of adrenaline, it was possible to
      demonstrate a statistically significant difference at the three measuring times.
      This suggests that especially the analyzed adrenaline level in the plasma could
      take on the role of a marker in cases of elevated intracranial pressure. In group
      2, with elevated intracranial pressure, the catecholamine levels in the
      cerebrospinal fluid (CSF) were considerably higher than those in group 1, but the
      difference did not reach the significance level. The lack of correlation between
      the catecholamine values in the plasma and CSF described in the literature
      (comparison of the corresponding values at time 2) was confirmed for
      noradrenaline and dopamine in patients with elevated intracranial pressure (group
      2). In both groups of patients there was a CSF plasma gradient for dopamine at
      time 2, i. e. the dopamine level was higher in cerebrospinal fluid than in the
      plasma. CONCLUSION: The study shows that even a slight rise in intracranial
      pressure without clinically detectable ischaemia may result in elevated plasma
      and CSF catecholamine levels. Although catecholamine values are not routine
      parameters, they can be used in developing procedures to protect the brain in
      neurosurgical patients.

PMID- 15486804
TI  - [The unexpectedly difficult airway -- a plea for the oxford-non-kinking-tube].
AB  - The skill to safely manage the unexpectedly difficult airway is expected from
      every anaesthetist. The strategies to safely overcome this severe problem have to
      be adapted to the given equipment and the individual aptitude and skills of the
      respective colleague. The algorithms for management of the difficult airway
      should be as simple as possible, and one cannot assume that devices for fibre
      optic intubation are available at every site. Indispensable, however, is the
      availability of face masks, naso- and oropharyngeal airways and laryngeal mask
      airways in different sizes at each induction site. This paper is especially
      devoted to recalling the Oxford non-kinking tube and its specific way of
      handling, as a lot of cases of unexpectedly difficult airway can be safely
      managed with this tool. Alternatives to safeguarding the difficult airway are the
      intubation laryngeal mask airway or the esophago-tracheal combitube. For managing
      the worst case, the "cannot ventilate - cannot intubate" disaster, instruments
      for percutaneous punction of the trachea and devices for oxygen insufflation must
      be readily available in every theatre.

PMID- 15486805
TI  - [Anesthesia in thoracic surgery].

PMID- 15486808
TI  - Insulin-dependent diabetes and gut dysfunction: the BB rat model.
AB  - Accumulating data indicate that intestinal dysfunction and dysregulation of the
      gut immune system may play a role in the development of type 1 diabetes. This
      review deals with the occurrence of gut damage and dysfunction in BB rats, an
      animal model of spontaneous immune type 1 diabetes, placing special emphasis on
      the effect of diet on the incidence of diabetes in BB rats, the identification of
      a type 1 diabetes-related protein from wheat, and preliminary observations
      documenting anomalies in the inductive tissues of the gut immune system (Peyer's
      patch cells and mesenteric lymph node cells) and pancreatic lymph node cells of
      diabetes-prone BB rats. In addition to histological evidence of gut damage, the
      review will also draw attention to altered intestinal disaccharidase activity,
      changes in intestinal peroxidase activity, glucagon-like peptide 1 anomalies, and
      perturbation of both intestinal permeability and mucin content in BB rats. In all
      these cases, the findings in rats fed a diabetes-promoting diet are compared to
      those collected in animals receiving a protective diabetes-retardant diet.

PMID- 15486809
TI  - Exendin-4 dose-dependently stimulates somatostatin and insulin secretion in
      perfused rat pancreas.
AB  - We have investigated the effect of exendin-4, a GLP-1 analogue, on somatostatin
      and insulin secretion in perfused rat pancreas. At constant glucose concentration
      within the type 2 diabetic range (9 mM), exendin-4 stimulated somatostatin and
      insulin secretion in a dose-dependent manner. Dose-response curves were sigmoidal
      (R (2) = 0.9954 and R (2) = 0.9973, respectively; p < 0.01) and the EC (50) was
      4.3 nM for somatostatin secretion and 1.4 nM for insulin secretion. Exendin-4
      stimulated somatostatin output at low (3.2 mM), normal (5.5 mM) and high (9 mM)
      glucose concentrations, while the insulinotropic effect of exendin-4 was not
      found at low glucose levels. On the other hand, exendin-4 potentiated
      somatostatin and insulin responses to an increase in perfusate glucose levels,
      and to arginine and carbachol. Finally, the insulinotropic effect of exendin-4
      was maintained in the absence of a somatostatin response as induced by cysteamine
      pretreatment, indicating a direct effect of exendin-4 on the B-cell. In summary,
      exendin-4 behaves as a general stimulatory agent of both insulin and somatostatin
      release in the perfused rat pancreas. Given that exendin-4 has also been shown to
      increase gastric somatostatin secretion, it is tempting to speculate that exendin
      4 might behave as a general stimulator of D-cell function in other tissues, a
      point worthy of further investigation.

PMID- 15486810
TI  - Effect of plasma free fatty acid concentration on the content and composition of
      the free fatty acid fraction in rat skeletal muscles.
AB  - Skeletal muscles contain a fraction of free (unesterified) fatty acids. This
      fraction is very small, but important since it contributes to the creation of the
      plasma-myocyte free fatty acid concentration gradient. Maintenance of this
      gradient is necessary for blood-borne fatty acids to be transported into the
      cell. There are no data on the regulation of the content and composition of the
      free fatty acid fraction in the cell. The aim of the present study was to examine
      the effect of an elevation and a reduction in the plasma-borne free fatty acid
      concentration on the content and composition of the free fatty acid fraction in
      different skeletal muscle types. The experiments were carried out on male Wistar
      rats with 280 - 310 g body weight. They were divided into four groups - 1,
      control; 2, exercised 3 h on a treadmill moving with a speed of 1,200 m/h and set
      at + 10 degrees incline; 3, treated with heparin; and 4, treated with nicotinic
      acid. Samples of the soleus as well as the red and white sections of the
      gastrocnemius muscles were taken. These muscles are composed mostly of slow
      twitch oxidative, fast-twitch oxidative-glycolytic and fast-twitch glycolytic
      fibres, respectively. Lipids were extracted from the muscle samples and from the
      blood; the free fatty acid fraction was isolated by means of thin-layer
      chromatography. The individual free fatty acids were identified and quantified
      using gas-liquid chromatography. The plasma concentration of free fatty acids was
      as follows: control group, 236.1 +/- 32.9; after exercise, 407.4 +/- 117.5; after
      heparin, 400.8 +/- 36.8; and after nicotinic acid, 102.5 +/- 26.1 micromol/l (p <
      0.01 vs. control values in each case). The total content of the free fatty acid
      fraction in the control group was as follows: white gastrocnemius, 27.6 +/- 7.3;
      red gastrocnemius, 52.2 +/- 13.9; soleus, 72.3 +/- 10.2 nmol/g. Elevation in
      plasma free acid concentration during exercise increased the total content of
      free fatty acids in the white gastrocnemius (38.7 +/- 13.9) and in the soleus
      (103.4 +/- 15.9 nmol/g; rest-exercise: p < 0.05 and p < 0.01, respectively), but
      had no effect in the red gastrocnemius. Neither elevation in the plasma free
      fatty acid concentration with heparin nor reduction with nicotinic acid affected
      the total content of the free fatty acid fraction in the muscles examined. The
      ratio of plasma concentration of individual acid to muscle concentration for the
      same acid varied greatly, depending on acid, muscle type and experimental group.
      The ratio was positive (above unity) for each acid almost in all cases with the
      exception of certain acids in the nicotinic acid-treated group where it was below
      unity. We conclude that the skeletal myocytes maintain a stable level of free
      fatty acid fraction in the wide range of plasma free fatty acid concentrations.

PMID- 15486811
TI  - Effects of growth hormone (GH) on mRNA levels of uncoupling proteins 1, 2, and 3
      in brown and white adipose tissues and skeletal muscle in obese mice.
AB  - We have investigated whether GH treatment influences the expression of UCP1, 2
      and 3 mRNA in a KK-Ay obese mouse model. KK-Ay mice (n = 10) and C57Bl/6J control
      mice (n = 10) were injected subcutaneously with human GH (1.0 mg/kg/day and 3.5
      mg/kg/day) for 10 days, and compared with mice injected with physical saline. The
      KK-Ay obese mice weighed significantly less (p < 0.01 : 1.0 mg/kg/day, p < 0.05 :
      3.5 mg/kg/day) and had smaller inguinal subcutaneous and perimetric white adipose
      tissue (WAT) pads (p < 0.05 : 3.5 mg/kg/day), but increased skeletal muscle
      weight (p < 0.05). The brown adipose tissue (BAT) weight did not change
      significantly. Not only plasma free fatty acid and glucose levels but also plasma
      insulin levels decreased. The reduced HOMA-IR (homeostasis model assessment
      insulin resistance) values suggested that insulin resistance was improved by GH
      treatment. UCP1 mRNA levels increased after the 3.5 mg GH treatment by 2.8-fold
      (p < 0.01 vs. saline controls) and 2.0-fold (p < 0.05 vs. 1 mg GH treatment) in
      BAT, and by 6.0-fold in subcutaneous WAT (p < 0.05 vs. controls). UCP2 mRNA
      levels increased 2.2-fold (p < 0.05 vs. control) and 2.1-fold (p < 0.05 vs. 1 mg
      GH treatment) in BAT, and 2.0-fold (p < 0.05 vs. controls) in skeletal muscle.
      One mg GH administration also stimulated UCP1 mRNA expression by 2.5-fold (p <
      0.05 vs. controls) and UCP3 mRNA expression by 2.8-fold (p < 0.05 vs. controls)
      in the muscle. On the other hand, lean mice showed no significant difference in
      body composition or plasma parameters. UCP1, 2 and 3 mRNA expression in lean mice
      did not show any significant change after treatment with GH. We conclude that GH
      treatment increased mRNA levels for not only UCP1, but also UCP 2 and 3 in BAT,
      WAT and muscle in a KK-Ay obese mouse model. These findings suggest that GH
      induced thermogenesis may contribute to the reduction in WAT and energy
      expenditure.

PMID- 15486812
TI  - Effect of testosterone on purine nucleotide metabolism in rat liver.
AB  - In previous studies, we found that castration induced interesting morphological
      and biochemical changes in rat liver. For the present study, we have examined the
      effects of testosterone on the kinetics of purine nucleotide metabolism with the
      aim of determining the steps affected by testosterone deficiency. A
      biomathematical model of purine nucleotide metabolism was used to analyze the
      many reactions involved. The model simplifies purine nucleotide metabolism to
      four main steps: 1) de novo synthesis from PRPP to IMP; 2) the inosinic branch
      point from IMP to GMP or AMP; 3) catabolism of IMP, AMP and GMP to uric acid; 4)
      RNA and DNA formation from AMP and GMP. We evaluated rate constants from each
      step from variations in specific radioactivity of metabolites labelled with (14)C
      formate, a precursor of de novo synthesis. The model was applied to the liver of
      normal and castrated rats before and after testosterone treatment. All four steps
      were slowed after castration, and were not completely restored by androgen
      administration. The model can give a clear representation of the kinetics of the
      reactions involved in the liver nucleotide metabolism investigated here, and we
      propose that a similar approach could be useful whenever a quantitative
      evaluation of the results obtained in vivo after administration of labelled
      precursors is required.

PMID- 15486813
TI  - Lack of effect of vitamin D administration during pregnancy and early life on
      diabetes incidence in the non-obese diabetic mouse.
AB  - BACKGROUND AND AIMS: Several studies have suggested that vitamin D
      supplementation in early life may reduce the risk of developing type 1 diabetes
      in later life. The non-obese diabetic (NOD) mouse is a model of spontaneous type
      1 diabetes currently used for testing hypothesis/compounds aimed at disease
      prevention. In this study, we tested the effect of vitamin D (16 IU by gavage) on
      diabetes incidence in NOD/Ba mice treated from conception with olive oil
      containing vitamin D via maternal dosing up to 10 weeks of age and followed up
      until 32 weeks of age. METHODS: Twelve breeding pairs were administered olive oil
      containing vitamin D during pregnancy, 15 days following the birth of the pups
      and for the next 10 weeks subsequently. The same breeding pairs were bred again
      after a clearance period of 15 days using a control solution to produce a control
      litter. This control group received a control solution for the same period of
      time. Diabetes incidence, degree of insulitis, and insulin content in the
      pancreas were investigated in the two groups. RESULTS: 12 vitamin D-treated NOD
      mice developed diabetes compared to 15 animals in the control group (Log rank
      test p = 0.899, NS). There were no significant differences between the groups in
      diabetes incidence, time of onset of the disease, degree of insulitis, or the
      insulin content in the pancreas. CONCLUSION: Vitamin D administered in utero and
      in the early stages of life at the dosage used does not change the incidence of
      diabetes or modify the disease process that leads to beta cell destruction in the
      NOD mouse.

PMID- 15486814
TI  - Absence of anorectic effect to acute peripheral leptin treatment in adult rats
      whose mothers were malnourished during lactation.
AB  - Diets with restricted energy or protein during lactation programs body weight in
      the adult offspring. We have investigated the hypothesis that protein or energy
      restricted diets during lactation alter the feeding response to peripheral leptin
      treatment of the adult offspring. Five Wistar rats were randomly assigned to one
      of the following groups on the day that the offspring were born: C, control diet
      with 23% protein; PR, protein restricted diet with 8% protein; and ER, energy
      restricted, receiving the control diet in restricted quantities, which were
      calculated according to the mean ingestion of the PR group. After weaning (day
      21), two animals from each litter (10 pups in each group) were randomly selected
      and placed together in the cage with free access to water and standard diet until
      150 days of age, when they were tested for its response to either leptin (0.5
      mg/kg body wt ip) for groups Clep, PRlep and ERlep or saline vehicle for groups
      Csal, PRsal and ERsal on food intake. In the control groups, food intake was
      reduced two hours (36%), four hours (41%) and six hours (25%) after leptin
      treatment. In contrast, no response was observed to leptin treatment in the PRlep
      and ERlep groups, suggesting leptin resistance. We demonstrated the development
      of resistance to the anorectic leptin effect and its program in a critical life
      period associated to nutritional and hormonal factors.

PMID- 15486815
TI  - Reduction of postprandial hyperglycemia in patients with type 2 diabetes reduces
      NF-kappaB activation in PBMCs.
AB  - AIMS/HYPOTHESIS: Short-lasting hyperglycemia results in activation of the
      transcription factor NF-kappaB in peripheral blood mononuclear cells. We
      therefore studied whether the postprandial increase in glucose is sufficient to
      induce mononuclear NF-kappaB activation and whether blunting postprandial
      hyperglycemia with the alpha-glucosidase inhibitor acarbose reduces NF-kappaB
      activation. METHODS: 20 patients with type 2 diabetes were included in a double
      blind randomized trial receiving 100 mg acarbose or placebo three times a day
      over a period of eight weeks. Peripheral blood mononuclear cells were isolated
      before and 120 minutes after a standardized breakfast. NF-kappaB binding activity
      was estimated by electrophoretic mobility shift assay and NF-kappaB-p65;
      translocation was determined by Western blot. RESULTS: Eight weeks of treatment
      with acarbose significantly reduced postprandial hyperglycemia (p = 0.004 when
      compared to placebo), postprandial mononuclear NF-kappaB-binding activity (p =
      0.045) and nuclear translocation of NF-kappaB-p65 (p = 0.02). CONCLUSION:
      Reduction of postprandial glucose peak levels by acarbose reduces postprandial
      mononuclear NF-kappaB activation.

PMID- 15486816
TI  - Muscle type dependent increase in intramyocellular lipids during prolonged
      fasting of human subjects: a proton MRS study.
AB  - The amount of intramyocellular lipids in skeletal muscle was assessed by proton
      magnetic resonance spectroscopy during a voluntary fasting period of 120 h in
      four healthy lean volunteers. The aim of the study was to determine whether
      muscular lipid uptake in the presence of high plasma lipid levels, or lipid
      oxidation due to lacking glycogen as a source of energy in musculature, are the
      dominant effects on intramyocellular lipid levels under fasting conditions in
      various muscle types. Intramyocellular lipids were quantified in the tibialis
      anterior (mixed type I and type II fibers, predominantly type II) and the soleus
      muscle (predominantly type I fibers) before and after 24 h, 72 h, and 120 h of
      fasting. An extreme increase in intramyocellular lipids to levels of 369 %
      (median) was found in the tibialis anterior muscle compared to baseline value
      (intramyocellular lipid level prior to fasting, set to 100 %; p = 0.02). The
      soleus muscle with clearly higher baseline content of intramyocellular lipids (2 
      4-fold compared to tibialis anterior) revealed slightly delayed and less
      pronounced uptake of intramyocellular lipids during fasting to 152 % (median)
      after 120 h (p = 0.02). The absolute increment in intramyocellular lipids (in
      terms of ratios between lipid and creatine signals) was also higher in tibialis
      anterior than in soleus (not statistically significant). These findings indicate
      augmentation of the intramyocellular lipid pool during long-term elevation of
      plasma FFA in the presence of low plasma insulin concentrations in both muscles
      investigated. The rate of muscular lipid oxidation during fasting is clearly
      lower than the increased uptake of FFA by myocytes.

PMID- 15486817
TI  - Reference values of thyroid volume in a healthy, non-iodine-deficient Spanish
      population.
AB  - Our aim was to assess reference values of thyroid volume by ultrasonography in
      healthy adult subjects. We conducted an epidemiological cross-sectional study
      where 880 subjects were randomly selected from the town census of L'Hospitalet de
      Llobregat after being invited to participate in our study directly by mail and
      phone call. We made a clinical history of each subject and determined serum
      thyrotropin, antiperoxidase antibodies, urinary iodine excretion and thyroid
      volume by ultrasonography. Subjects with thyroid disease were excluded. We
      finally studied 268 representative subjects. The reference thyroid volume was
      median 7.31 ml, mean 8.22 ml (Confidence Interval: 7.75 - 8.69 ml). In men:
      median 9.19 ml, mean 9.87 ml (CI: 9.09 - 10.65 ml); in women: median 6.19 ml,
      mean 6.57 ml (CI: 6.22 - 9.92 ml) (p < 0.0001). We grouped the subjects into
      decades, and found that thyroid volume was different (p = 0.0034) in males
      because the younger group had lower volume. We did not find any differences among
      age groups in women. The mean of the urinary iodine excretion was 154.23
      microg/l. We have determined reference values of thyroid volume measured by
      ultrasonography in our iodine non-deficient population and prepared tables that
      distribute thyroid volume by sex and age.

PMID- 15486818
TI  - Depression and anxiety in different thyroid function states.
AB  - Previous studies on hypothyroid subjects have indicated serious psychiatric
      symptoms affecting the patients' quality of life. The present prospective cross
      sectional study's aim was to examine these symptoms in thyroid patients with
      different functional states. A total of 254 patients (age: 56 +/- 14 years [mean
      +/- standard deviation], 181 female, 73 male) referred to a hospital for
      radioiodine treatment of hyperthyroidism or for follow-up of differentiated
      thyroid cancer, respectively, were included. All patients underwent the twelve
      item general health questionnaire, which is an instrument for detecting mood
      disturbances. Euthyroid and hyperthyroid patients did not differ significantly in
      their general health questionnaire score (11 +/- 5 vs. 11 +/- 7), nor did
      subclinical hyperthyroid (11 +/- 6) or subclinical hypothyroid subjects (12 +/-
      5). In contrast, hypothyroid patients showed a significantly higher mean score
      (17 +/- 7, p < 0.001, ANOVA). Binary logistic regression revealed that
      hypothyroidism increases age and gender-adjusted risk for critical mood
      deterioration by seven-fold. Thus, hypothyroidism represents a widely
      underestimated functional condition that may severely affect mental health.

PMID- 15486819
TI  - Active ghrelin levels in women with polycystic ovary syndrome.

PMID- 15486820
TI  - Three new thermotolerant methylotrophic yeasts, Candida krabiensis sp. nov.,
      Candida sithepensis sp. nov., and Pichia siamensis sp. nov., isolated in
      Thailand.
AB  - Five strains of thermotolerant methylotrophic yeasts isolated in Thailand were
      found to represent three new species in the genera Pichia and Candida, based on
      phylogenetic analysis of D1/D2 domain of 26S rDNA, in addition to the
      morphological, physiological, biochemical and chemotaxonomic characterization.
      Three strains, FS96 and FS101 from flowers and M02 from tree flux, were
      characterized by ubiquinone Q7, multilateral budding, and the formation of hat
      shaped ascospores that are liberated at maturation. These strains showed
      identical nucleotide sequences in the D1/D2 domain and formed a cluster with
      Candida thermophila, "Pichia salicis" and Pichia angusta. They differed by 1.9%
      of nucleotide substitutions from Candida thermophila, the nearest species. They
      were considered to represent a single new species and are described as Pichia
      siamensis sp. nov. Two strains, N051 and S023, isolated from soil did not produce
      ascospores, proliferated by multilateral budding, did not demonstrate urease or
      DBB color reaction, and lacked sexual stages. These characteristics correspond to
      the genus Candida. Strains N051 and S023 differed by 2.8% and 1.9% of nucleotide
      substitutions in the D1/D2 domain from the nearest species, Candida nemodendra
      and Candida ovalis, respectively, and are considered to represent respective new
      species. N051 and S023 are described as Candida krabiensis sp. nov. and Candida
      sithepensis sp. nov., respectively.

PMID- 15486821
TI  - Phylogenetic analyses of the nitrogen-fixing genus Derxia.
AB  - Phylogenetic analyses of the 16S rRNA gene sequence indicate that the genus
      Derxia forms a distinct lineage in the beta-Proteobacteria. On the NJ tree Derxia
      has a low bootstrap value (30.9%) with Alcaligeneceae, and on the ML tree it
      shows an independent cluster separated from other families. Moreover, there is
      below 93.4% 16S rDNA sequence similarity between genus Derxia and the genera of
      the beta-Proteobacteria. These facts reveal that Derxia is not grouped with any
      known family of beta-Proteobacteria and should be placed as a separate genus of
      beta-Proteobacteria. The data on high G+C content (71 mol%), the cellular fatty
      acid composition, and the physiological characteristics of facultative hydrogen
      autotrophy and nitrogen fixation are unique for Derxia. The nifH gene sequence
      was found in this genus and phylogenetically compared among nitrogen-fixing
      bacteria to indicate that Derxia is clustered with the diazotrophs of beta
      Proteobacteria.

PMID- 15486822
TI  - PCR detection of hemolysin (vhh) gene in Vibrio harveyi.
AB  - The Vibrio harveyi hemolysin gene (vhh), which encodes for a virulence factor
      involved in pathogenicity to fish and shellfish species, may be targeted for
      species detection or strain differentiation. Primers designed for this gene were
      used in detection studies of V. harveyi strains from various hosts. One primer
      set among four tested, could amplify the expected gene fragment in PCR using
      templates from all 11 V. harveyi strains studied. Detection of the presence of
      the hemolysin gene could therefore serve as a suitable detection marker of Vibrio
      harveyi isolates potentially pathogenic to fish and shrimps.

PMID- 15486823
TI  - Rhodanobacter fulvus sp. nov., a beta-galactosidase-producing
      gammaproteobacterium.
AB  - A taxonomic study was carried out on a bacterial strain designated as Jip2T
      isolated from a soil sample mixed with rotten rice straw. It was a Gram-negative,
      aerobic, motile, and rod-shaped bacterium. It grew well on nutrient agar medium
      and utilized a fairly narrow spectrum of carbon source. The G+C content of the
      genomic DNA was 65.3 mol%. The major ubiquinone was Q-8. The major fatty acids
      were branched fatty acids, especially large amounts of iso C15:0 and iso C17:1
      w9c were detected in the cells grown on TSA agar for 24 h. Comparative 16S rDNA
      study showed a clear affiliation of this bacterium to the genus Rhodanobacter.
      The 16S rDNA sequence of strain Jip2T showed 96.4% sequence similarity to that of
      Rhodanobacter lindaniclasticus RP5575T. On the basis of phenotypic
      characteristics and 16S rDNA sequence analysis, strain Jip2T is clearly distinct
      from Rhodanobacter lindaniclasticus. We propose the name Rhodanobacter fulvus sp.
      nov. for strain Jip2T (=IAM 15025T=KCTC 12098T).

PMID- 15486824
TI  - Optimization of bacteriocin production by Lactobacillus plantarum ST13BR, a
      strain isolated from barley beer.
AB  - The cell-free supernatant containing bacteriocin ST13BR, produced by
      Lactobacillus plantarum ST13BR, inhibits the growth of L. casei, Pseudomonas
      aeruginosa, Enterococcus faecalis, Klebsiella pneumoniae and Escherichia coli.
      Based on tricine-SDS-PAGE, bacteriocin ST13BR is 10 kDa in size. Complete
      inactivation or significant reduction in bacteriocin activity was observed after
      treatment with Proteinase K, trypsin and pronase, but not with catalase or alpha
      amylase. Low bacteriocin activity (200 AU/ml) was recorded in BHI medium, M17
      broth, 10% (w/v) soy milk, and 2% and 10% (w/v) molasses, despite good growth.
      Maximal bacteriocin activity (6,400 AU/ml) was recorded after 23 h in MRS broth,
      but only at 30 degrees C. Tween 80 in MRS broth increased bacteriocin production
      by more than 50%. Meat extract or yeast extract as sole nitrogen source, or a
      combination of the two (1 : 1) in MRS broth, stimulated bacteriocin production
      (6,400 AU/ml). Only 50% activity (3,200 AU/ml) was recorded with tryptone as sole
      nitrogen source, whereas a combination of tryptone, meat extract and yeast
      extract yielded 6,400 AU/ml. Bacteriocin production was not stimulated by the
      addition of glucose at 2.0% w/v (3,200 AU/ml), nor 2% (w/v) fructose, sucrose,
      lactose or mannose, respectively (800 AU/ml). Activity levels less than 200 AU/ml
      were recorded in the presence of 0.05% to 0.5% (w/v) maltose. Maximal bacteriocin
      production (6,400 AU/ml) was recorded in the presence of 2% (w/v) maltose.
      Maltose at 4.0% (w/v) led to a 50% reduction of bacteriocin activity. The
      presence of 1.0% (w/v) and higher KH(2)PO(4), or glycerol at 0.2% (w/v)
      suppressed bacteriocin production.

PMID- 15486825
TI  - Gluconobacter thailandicus sp. nov., an acetic acid bacterium in the alpha
      Proteobacteria.
AB  - Four strains of acetic acid bacteria were isolated from flowers collected in
      Thailand. In phylogenetic trees based on 16S rRNA gene sequences and 16S-23S rDNA
      internal transcribed spacer (ITS) region sequences, the four isolates were
      located in the lineage of the genus Gluconobacter and constituted a separate
      cluster from the known Gluconobacter species, Gluconobacter oxydans,
      Gluconobacter cerinus, and Gluconobacter frateurii. In addition, the isolates
      were distinguished from the known species by restriction analysis of 16S-23S rDNA
      ITS region PCR products using three restriction endonucleases Bsp1286I, MboII,
      and AvaII. The DNA base composition of the isolates ranged from 55.3-56.3 mol%
      G+C. The four isolates constituted a taxon separate from G. oxydans, G. cerinus,
      and G. frateurii on the basis of DNA-DNA similarities. Morphologically,
      physiologically, and biochemically, the four isolates were very similar to the
      type strains of G. oxydans, G. cerinus, and G. frateurii; however, the isolates
      were discriminated in their growth at 37 degrees C from the type strains of G.
      cerinus and G. frateurii, and in their growth on L-arabitol and meso-ribitol from
      the type strain of G. oxydans. The isolates showed no acid production from myo
      inositol or melibiose, which differed from the type strains of the three known
      species. The major ubiquinone homologue was Q-10. On the basis of the results
      obtained, Gluconobacter thailandicus sp. nov. was proposed for the four isolates.
      The type strain is isolate F149-1(T) (=BCC 14116(T)=NBRC 100600(T)=JCM
      12310(T)=TISTR 1533(T)=PCU 225(T)), which had 55.8 mol% G+C, isolated from a
      flower of the Indian cork tree (Millingtonia hortensis) collected in Bangkok,
      Thailand.

PMID- 15486826
TI  - Molecular basis of ML-236B production in the high-producing mutant No. 41520 of
      Penicillium citrinum.
AB  - Strain improvement through random mutagenesis, screening and selection has
      provided us with spontaneous mutants which could produce more ML-236B than the
      original isolate, Penicillium citrinum SANK18767. The objective of the present
      study is to clarify how a high-producing mutant No. 41520 acquired the ability to
      produce 500 times more ML-236B than the original isolate on a molecular basis.
      Southern blot analysis and sequence comparison revealed that amplification of the
      ML-236B biosynthetic gene cluster and alteration of nucleotides within the loci
      had not occurred in the genome of No. 41520. On the other hand, a differential
      hybridization and Northern blot analysis showed that expression levels of the
      nine biosynthetic genes mlcA to mlcH and mlcR in No. 41520 increased greatly as
      compared to those in the original isolate. These data suggested that the increase
      in ML-236B production was partly due to increased expression of genes involved in
      ML-236B biosynthesis. Morphological differences and higher consumption of carbon
      source would also affect ML-236B production in No. 41520. Functional analysis
      revealed that a gene, orf1 next to mlcR, was not involved in the ML-236B
      biosynthesis, but it was involved in the transcriptional activation of genes
      along with the ML-236B gene cluster. Titer enhanced mutations might have occurred
      in the regulation system for transcription activation of the ML-236B biosynthetic
      genes in the mutants of P. citrinum.

PMID- 15486827
TI  - PCR cloning and heterologous expression of chitinase gene of endophytic
      Streptomyces aureofaciens CMUAc130.

PMID- 15486828
TI  - A combined linkage-physical map of the human genome.
AB  - We have constructed de novo a high-resolution genetic map that includes the
      largest set, to our knowledge, of polymorphic markers (N=14,759) for which
      genotype data are publicly available; that combines genotype data from both the
      Centre d'Etude du Polymorphisme Humain (CEPH) and deCODE pedigrees; that
      incorporates single-nucleotide polymorphisms; and that also incorporates sequence
      based positional information. The position of all markers on our map is
      corroborated by both genomic sequence and recombination-based data. This specific
      combination of features maximizes marker inclusion, coverage, and resolution,
      making this map uniquely suitable as a comprehensive resource for determining
      genetic map information (order and distances) for any large set of polymorphic
      markers.

PMID- 15486830
TI  - Paradoxical inflammatory reaction during treatment of Cryptococcus neoformans
      var. gattii meningitis in an HIV-seronegative woman.
AB  - A human immunodeficiency virus (HIV)-seronegative woman was admitted to the
      hospital with postpartum onset Cryptococcus neoformans var. gattii meningitis and
      markedly increased intracranial pressure. A poor initial response to antifungal
      therapy was followed, 2 months after hospital admission, by severe acute
      meningeal and cerebral inflammation and clearance of yeast cells from
      cerebrospinal fluid. This first reported case of paradoxical inflammatory
      reaction to C. neoformans illustrates important aspects of the host-pathogen
      interaction and highlights possible effects of immunomodulatory therapies.

PMID- 15486829
TI  - A common mutation is associated with a mild, potentially asymptomatic phenotype
      in patients with isovaleric acidemia diagnosed by newborn screening.
AB  - Isovaleric acidemia (IVA) is an inborn error of leucine metabolism that can cause
      significant morbidity and mortality. Since the implementation, in many states and
      countries, of newborn screening (NBS) by tandem mass spectrometry, IVA can now be
      diagnosed presymptomatically. Molecular genetic analysis of the IVD gene for 19
      subjects whose condition was detected through NBS led to the identification of
      one recurring mutation, 932C-->T (A282V), in 47% of mutant alleles. Surprisingly,
      family studies identified six healthy older siblings with identical genotype and
      biochemical evidence of IVA. Our findings indicate the frequent occurrence of a
      novel mild and potentially asymptomatic phenotype of IVA. This has significant
      consequences for patient management and counseling.

PMID- 15486831
TI  - Randomized trial of 3-dose regimens of tafenoquine (WR238605) versus low-dose
      primaquine for preventing Plasmodium vivax malaria relapse.
AB  - BACKGROUND: Tafenoquine is an 8-aminoquinoline developed as a more effective
      replacement for primaquine. In a previous dose-ranging study in Thailand, 3
      tafenoquine regimens with total doses ranging from 500 mg to 3000 mg prevented
      relapse of Plasmodium vivax malaria in most patients when administered 2 days
      after receipt of a blood schizonticidal dose of chloroquine. METHODS: To improve
      convenience and to begin comparison of tafenoquine with primaquine, 80 patients
      with P. vivax infection were randomized to receive 1 of the following 5
      treatments 1 day after receiving a blood schizonticidal dose of chloroquine: (A)
      tafenoquine, 300 mg per day for 7 days (n=18); (B) tafenoquine, 600 mg per day
      for 3 days (n=19); (C) tafenoquine, 600 mg as a single dose (n=18); (D) no
      further treatment (n=13); or (E) primaquine base, 15 mg per day for 14 days
      (n=12). The minimum duration of protocol follow-up was 8 weeks, with additional
      follow-up to 24 weeks. RESULTS: Forty-six of 55 tafenoquine recipients, 10 of 13
      recipients of chloroquine only, and 12 of 12 recipients of chloroquine plus
      primaquine completed at least 8 weeks of follow-up (or had relapse). There was 1
      relapse among recipients of chloroquine plus tafenoquine, 8 among recipients of
      chloroquine only, and 3 among recipients of chloroquine plus primaquine. The rate
      of protective efficacy (determined on the basis of reduction in incidence
      density) for all recipients of chloroquine plus tafenoquine, compared with
      recipients of chloroquine plus primaquine, was 92.6% (95% confidence interval,
      7.3%-99.9%; P=.042, by Fisher's exact test). CONCLUSIONS: Tafenoquine doses as
      low as a single 600-mg dose may be useful for prevention of relapse of P. vivax
      malaria in Thailand.

PMID- 15486832
TI  - Malaria in travelers: a review of the GeoSentinel surveillance network.
AB  - BACKGROUND: Malaria is a common and important infection in travelers. METHODS: We
      have examined data reported to the GeoSentinel surveillance network to highlight
      characteristics of malaria in travelers. RESULTS: A total of 1140 malaria cases
      were reported (60% of cases were due to Plasmodium falciparum, 24% were due to
      Plasmodium vivax). Male subjects constituted 69% of the study population. The
      median duration of travel was 34 days; however, 37% of subjects had a travel
      duration of < or =4 weeks. The majority of travellers did not have a pretravel
      encounter with a health care provider. Most cases occurred in travelers (39%) or
      immigrants/refugees (38%). The most common reasons for travel were to visit
      friends/relatives (35%) or for tourism (26%). Three-quarters of infections were
      acquired in sub-Saharan Africa. Severe and/or complicated malaria occurred in 33
      cases, with 3 deaths. Compared with others in the GeoSentinel database, patients
      with malaria had traveled to sub-Saharan Africa more often, were more commonly
      visiting friends/relatives, had traveled for longer periods, presented sooner
      after return, were more likely to have a fever at presentation, and were less
      likely to have had a pretravel encounter. In contrast to immigrants and visitors
      of friends or relatives, a higher proportion (73%) of the missionary/volunteer
      group who developed malaria had a pretravel encounter with a health care
      provider. Travel to sub-Saharan Africa and Oceania was associated with the
      greatest relative risk of acquiring malaria. CONCLUSIONS: We have used a global
      database to identify patient and travel characteristics associated with malaria
      acquisition and characterized differences in patient type, destinations visited,
      travel duration, and malaria species acquired.

PMID- 15486833
TI  - Maternal genital colonization with Ureaplasma urealyticum promotes preterm
      delivery: association of the respiratory colonization of premature infants with
      chronic lung disease and increased mortality.
AB  - BACKGROUND: Infection of the chorioamnion with Ureaplasma urealyticum has been
      associated with low birth weight. Respiratory tract colonization in preterm
      infants has been associated with the development of chronic lung disease (CLD).
      The purpose of the present study was to determine the frequency of colonization
      of the mother's vagina and the preterm infant's respiratory tract and to
      associate U. urealyticum with premature birth and with development of CLD in the
      newborn. METHODS: The present prospective study involved 126 mothers with preterm
      delivery and 125 mothers with full-term delivery, as well as their offspring.
      Vaginal secretion specimens were obtained from each mother before delivery.
      Rhinopharyngeal secretion or tracheal lavage specimens were collected after the
      birth of each premature and full-term infant and then periodically during
      hospitalization. RESULTS: Vaginal Ureaplasma colonization occurred among 36.5% of
      mothers with preterm delivery and among 38% of mothers with full-term delivery.
      The rate of vertical transmission was 33% and 17% for mothers with preterm
      delivery and mothers with full-term delivery, respectively. The transmission rate
      for infants, according to birth weight, was as follows: 60%, for infants with a
      birth weight of <1000 g; 50%, for infants with a birth weight of 1000-1500 g; and
      15.3%, for infants with a birth weight of > or =1500 g (P=.001). The median
      gestational age of preterm infants born to colonized mothers was 28.5 weeks, and
      that of preterm infants born to noncolonized mothers was 32 weeks (P<.0001). The
      median birth weight of colonized preterm infants was 1135 g, and that of
      noncolonized infants was 1670 g (P<.0001). Twenty-four percent of preterm infants
      and 10% of full-term infants were colonized with U. urealyticum. Of colonized
      preterm infants, 27% developed CLD, compared with 9% of noncolonized infants
      (P=.03). Mortality was significantly higher among colonized preterm infants
      (P=.003). CONCLUSIONS: The rate of vertical transmission is highest among preterm
      infants with a birth weight of <1500 g. Vaginal colonization with Ureaplasma
      organisms is associated with premature delivery. Colonization of the respiratory
      tract of infants is associated with the development of CLD and with increased
      mortality.

PMID- 15486834
TI  - Tropical pulmonary eosinophilia: a case series in a setting of nonendemicity.
AB  - BACKGROUND: Tropical pulmonary eosinophilia (TPE) is a rare but serious
      manifestation of infection with the lymphatic filarial parasites Wuchereria
      bancrofti and Brugia malayi. Although endemicity is limited to the tropical and
      subtropical regions of Africa, South America, and Asia, immigration and travel
      practices have led to the diagnosis of TPE in areas of nonendemicity. METHODS: We
      herein present a case series of all patients with TPE who presented to the
      Toronto General Hospital during 1990-2003. RESULTS: Seventeen individuals
      presented with TPE during the study period, and all were of South Asian ancestry.
      All 17 received an incorrect diagnosis at presentation (median number of
      consultations before diagnosis, 2), the most frequent of which was asthma (76%).
      Eosinophil count, serum immunoglobulin E levels, and anti-filarial antibody
      titers were elevated in all patients. Ten of 14 patients had an abnormal chest
      radiograph finding, and 11 of 12 patients had abnormal results of pulmonary
      function tests. CONCLUSIONS: TPE is an important diagnostic consideration in
      patients with eosinophilia, respiratory symptoms, and history of exposure to this
      disease. In the untreated individual, TPE can lead to chronic and progressive
      respiratory compromise and death. Prompt recognition and treatment with
      diethylcarbamazine is therefore key to minimizing morbidity and mortality.

PMID- 15486835
TI  - Multicenter study of a rapid molecular-based assay for the diagnosis of group B
      Streptococcus colonization in pregnant women.
AB  - BACKGROUND: Current prevention of infection due to group B Streptococcus (GBS)
      involves giving intrapartum antibiotics to women on the basis of either antenatal
      culture colonization status or presence of risk factors. METHODS: We
      prospectively compared the performance characteristics of a rapid molecular
      diagnostic test (IDI-Strep B; Infectio Diagnostic) with culture for intrapartum
      GBS detection after 36 weeks' gestation in 5 North American centers during the
      period September 2001-May 2002. Antenatal GBS screening was done according to the
      usual practice of participating hospitals. Two combined vaginal/anal specimens
      were obtained from participants during labor by use of standard techniques and
      processed by the same laboratories that processed the antenatal specimens. Each
      swab sample was processed simultaneously by culture and with IDI-Strep B. The
      collected specimens were randomized for order of testing of the swab samples by
      culture or the rapid test. RESULTS: Of enrolled women, 803 (91.1%) were eligible
      for analysis. The overall intrapartum GBS colonization rate by culture was 18.6%
      (range, 9.1%-28.7%). Compared with intrapartum culture, the molecular test had a
      sensitivity of 94.0% (range, 90.1%-97.8%), specificity of 95.9% (range, 94.3%
      97.4%), positive predictive value of 83.8% (range, 78.2%-89.4%), and negative
      predictive value of 98.6% (range, 97.7%-99.5%). The molecular test was superior
      to antenatal cultures (sensitivity, 94% vs. 54%; P<.0001) and prediction of
      intrapartum status on the basis of risk factors (sensitivity, 94% vs. 42%;
      P<.0001). CONCLUSION: Use of this test for determination of GBS colonization
      during labor is highly sensitive and specific and may lead to a further reduction
      in rates of neonatal GBS disease.

PMID- 15486836
TI  - The past and future of perinatal group B streptococcal disease prevention.

PMID- 15486837
TI  - Randomized comparison of chloroquine plus sulfadoxine-pyrimethamine versus
      artesunate plus mefloquine versus artemether-lumefantrine in the treatment of
      uncomplicated falciparum malaria in the Lao People's Democratic Republic.
AB  - BACKGROUND: Recent clinical trials in the Lao People's Democratic Republic have
      demonstrated that chloroquine and sulfadoxine-pyrimethamine, which are national
      malaria treatment policy, are no longer effective in the treatment of
      uncomplicated Plasmodium falciparum malaria. METHODS: A randomized comparison of
      3 oral antimalarial combinations--chloroquine plus sulfadoxine-pyrimethamine
      versus artesunate plus mefloquine versus artemether-lumefantrine--with 42-day
      follow-up period, was conducted among 330 patients with acute uncomplicated
      falciparum malaria in southern Laos. RESULTS: The 42-day cure rates, as
      determined by intention-to-treat analysis and adjusted for reinfection, were
      100%, 97%, and 93% for the groups receiving artesunate plus mefloquine,
      artemether-lumefantrine, and chloroquine plus sulfadoxine-pyrimethamine,
      respectively. Of 8 patients receiving chloroquine plus sulfadoxine-pyrimethamine
      who experienced treatment failure, 6 had early treatment failure. The mean
      parasite clearance time was significantly longer in patients treated with
      chloroquine plus sulfadoxine-pyrimethamine (2.9 days; 95% confidence interval
      [CI], 2.8-3.0 days) than in those treated with artesunate plus mefloquine (2.07
      days; 95% CI, 2.0-2.1 days; P<.001) and artemether-lumefantrine (2.08 days; 95%
      CI, 2.0-2.1 days; P<.001). Cure rates with artemether-lumefantrine were high
      despite low mean daily dietary fat intake (13.8 g; 95% CI, 12.5-15.1 g) and day 7
      plasma lumefantrine concentrations (0.47 mu g/mL; 95% CI, 0.38-0.56 mu g/mL).
      CONCLUSION: Oral artesunate plus mefloquine and artemether-lumefantrine are
      highly effective for the treatment of uncomplicated falciparum malaria in Laos.

PMID- 15486838
TI  - An outbreak of conjunctivitis due to a novel unencapsulated Streptococcus
      pneumoniae among military trainees.
AB  - BACKGROUND: Bacterial conjunctivitis usually occurs as sporadic cases; outbreaks
      are uncommon and usually are associated with school campuses. We report an
      outbreak of Streptococcus pneumoniae conjunctivitis at a military training
      facility. METHODS: An outbreak investigation was done. Each case of
      conjunctivitis was evaluated with an assessment tool including demographic and
      clinical data. Conjunctival swabs were obtained. Pneumococci underwent standard
      testing, including serotyping with the Quellung reaction, capsular staining, and
      multilocus sequence typing. Sequence types were compared with previous reported
      outbreak strains by construction of dendrograms. Carriage rates of S. pneumoniae
      were determined among previously undiagnosed case patients with conjunctivitis,
      and a case-control study was performed. Control measures included education to
      increase hand washing, distribution of alcohol-based hand gel, and prompt
      treatment of patients with conjunctivitis. RESULTS: During a 6-week period, 92
      cases of conjunctivitis occurred among 3500 persons, with an attack rate of 1.75
      cases per 100 person-months. Eighty cases (87%) were due to S. pneumoniae; 45
      (49%) were confirmed, and 35 (38%) were probable. Ten percent of recruits
      surveyed carried the outbreak strain. Twenty-two percent self-reported symptoms
      consistent with conjunctivitis during the outbreak period; sharing washcloths was
      associated with conjunctivitis (odds ratio, 11.7; P=.03). The causative organism
      was resistant to azithromycin but susceptible to telithromycin. The outbreak
      strain was an unencapsulated S. pneumoniae that has not been previously
      described; it was most closely related to the sequence type causing the Dartmouth
      College (Hanover, NH) outbreak of conjunctivitis in 2002. CONCLUSIONS: We report
      a conjunctivitis outbreak among military trainees caused by a novel,
      unencapsulated strain of S. pneumoniae.

PMID- 15486839
TI  - Specific immunoglobulin A antibodies in maternal milk and delayed Helicobacter
      pylori colonization in Gambian infants.
AB  - BACKGROUND: Immunoglobulin A (IgA) in maternal milk may protect Gambian infants
      from early Helicobacter pylori colonization. This study sought evidence that this
      protection could be due to specific IgA antibodies. METHODS: Sixty-five infants
      were screened from 12 weeks of age with [13C]-urea breath tests. Antibodies in
      maternal milk were measured to determine total IgA content and to detect specific
      IgA antibodies against crude whole-cell and recombinant H. pylori urease antigen
      preparations. RESULTS: Ten children (15%) had no evidence of early H. pylori
      colonization, 10 (15%) had early H. pylori colonization, and 43 (66%) had mixed
      results. Levels of maternal circulating specific immunoglobulin G, total milk
      IgA, and IgA directed against crude whole-cell H. pylori antigen preparation were
      not significantly associated with the rate of infant H. pylori colonization.
      However, mothers of infants with no evidence of early colonization produced
      significantly higher levels of anti-recombinant urease IgA antibodies in milk
      than did control mothers, particularly at 8, 16, and 20 weeks postpartum (P<.01).
      CONCLUSIONS: These observations support the hypothesis that antibodies in
      mother's milk directed against H. pylori urease can protect against colonization
      in human infancy.

PMID- 15486840
TI  - Bloodstream infections: a trial of the impact of different methods of reporting
      positive blood culture results.
AB  - BACKGROUND: The impact of how positive blood culture results are reported on the
      evolution bloodstream infections (BSIs) has not been assessed. METHODS: We
      randomly assigned patients with BSIs into 3 groups: group A (for which physicians
      received a conventional report), group B (for which physicians received a
      conventional report and a written alert on the chart with clinical advice), and
      group C (for which physicians received the above plus oral clinical advice). The
      adequacy of therapy before and after receipt of the different types of
      information was assessed. RESULTS: Overall, 297 episodes (109 in group A, 99 in
      group B, and 89 in group C) were studied. Patients who received inadequate
      treatment before receiving microbiological information had a longer mean (+/-SD)
      hospital stay (27.2+/-32.4 vs. 19.4+/-15.8 days; P=.017), a higher mean risk of
      Clostridium difficile-associated diarrhea (8.3% vs. 1.9%; P=.013), a higher mean
      overall mortality rate (30.8% vs. 19.4%; P=.025), and a higher mean risk of
      infection-related mortality (23.3% vs. 13.6%; P=.031). After receipt of
      microbiological reports, recommendations for changes in therapy were issued for
      patients in groups B (52.3%) and C (53.1%). For groups A, B, and C, the
      proportions of days on which adequate treatment was received were 66.3%, 92.1%,
      and 91.2% (P<.001); the mean numbers of defined daily doses of appropriate
      antibiotic therapy were 16.4, 22.2, and 20.7 (P=.003); the mean durations of
      hospital stay were 19.8, 23.6, and 24.1 days (P=.761); and the mortality rates
      during the late period were 12.9%, 15.6%, and 11% (P=.670), respectively. The
      mean costs of antimicrobials per episode in groups A, B, and C were 580.63,
      537.98, and 434.53 (US707.85 dollars, US699.73 dollars, and US529.73 dollars,
      respectively). CONCLUSIONS: Written- or oral-alert reports with clinical advice
      should complement traditional microbiological reports for patients with BSIs.

PMID- 15486841
TI  - Empiric antimicrobial therapy for bacteremia: get it right from the start or get
      a call from infectious disease.

PMID- 15486842
TI  - Treating acute infections by telemedicine in the home.
AB  - Patients with community-acquired pneumonia, cellulitis, or urinary tract
      infection may be treated either in the hospital or as outpatients, depending on
      the severity of their disease, comorbidities, and Karnofsky performance status.
      To more efficiently use hospital beds, we discharge many moderately to severely
      ill patients with acute infections directly from the emergency department or
      early in the course of hospitalization. To insure satisfactory clinical outcomes,
      we use telemedicine in the home to monitor patients who would normally be
      hospitalized. Patients treated with telemedicine have satisfactory clinical
      outcomes, and their recovery appears to be more rapid than comparable
      hospitalized patients. Telemedicine in the home results in considerable savings
      by averting or shortening hospital stays.

PMID- 15486843
TI  - Contamination, disinfection, and cross-colonization: are hospital surfaces
      reservoirs for nosocomial infection?
AB  - Despite documentation that the inanimate hospital environment (e.g., surfaces and
      medical equipment) becomes contaminated with nosocomial pathogens, the data that
      suggest that contaminated fomites lead to nosocomial infections do so indirectly.
      Pathogens for which there is more-compelling evidence of survival in
      environmental reservoirs include Clostridium difficile, vancomycin-resistant
      enterococci, and methicillin-resistant Staphylococcus aureus, and pathogens for
      which there is evidence of probable survival in environmental reservoirs include
      norovirus, influenza virus, severe acute respiratory syndrome-associated
      coronavirus, and Candida species. Strategies to reduce the rates of nosocomial
      infection with these pathogens should conform to established guidelines, with an
      emphasis on thorough environmental cleaning and use of Environmental Protection
      Agency-approved detergent-disinfectants.

PMID- 15486844
TI  - Adherence to highly active antiretroviral therapy in the homeless population in
      San Francisco: a prospective study.
AB  - BACKGROUND: We examined adherence to highly active antiretroviral therapy (HAART)
      in the homeless population, a population thought to be at high risk for poor
      adherence to therapy and for development of drug-resistant strains of human
      immunodeficiency virus (HIV). METHODS: We performed a 12-month prospective study
      of 148 persons receiving HAART who were identified in a stratified screening of
      the homeless and marginally housed. We sampled in lunch lines, shelters, and
      hotels in 3 neighborhoods of San Francisco, California. We used pill counts at
      unannounced home visits as the primary measure of adherence. RESULTS: Of 148
      individuals sampled, 46 (31%) discontinued HAART during the study. Average
      adherence in the group of those who discontinued HAART was 51%, and 9% of these
      subjects had undetectable virus loads (i.e., <400 copies/mL) at the last follow
      up visit. Predictors of discontinuation of therapy were depressive symptoms,
      injection drug use, African American ethnicity, and early poor adherence. Of 148
      subjects, 102 (69%) continued to receive HAART throughout the study period.
      Average adherence in the group of those who continued to receive HAART was 74%,
      and 55% of these subjects had undetectable virus loads at the last follow-up
      visit. Predictors of lower average adherence in this group were African American
      ethnicity and use of crack cocaine; men who had sex with men had higher
      adherence. CONCLUSIONS: One-third of homeless and marginally housed persons
      receiving HAART discontinued therapy during the follow-up period and would
      benefit from adherence interventions directed at sustaining therapy; two-thirds
      continued to receive therapy at adherence levels comparable to those found with
      other clinical populations.

PMID- 15486845
TI  - Association between renal disease and outcomes among HIV-infected women receiving
      or not receiving antiretroviral therapy.
AB  - BACKGROUND: The associations of proteinuria and an elevated creatinine level with
      progression to acquired immunodeficiency syndrome (AIDS) and death in the era of
      highly antiretroviral therapy (HAART) have not been fully described. METHODS:
      This analysis includes 2038 human immunodeficiency virus (HIV)-infected women
      from the Women's Interagency HIV Study. Time to the development of a new AIDS
      defining illness (ADI) and death was modeled using proportional hazards
      regression before the widespread availability of HAART and after initiation of
      HAART. RESULTS: Of the 2038 subjects, the 14.1% of women with proteinuria had
      lower CD4 lymphocyte counts and higher viral loads (P<.0001 for all) at baseline
      and before initiation of HAART. Before the widespread availability of HAART,
      proteinuria was associated with an increased risk for development of ADI (hazard
      ratio [HR], 1.37; P=.005), and proteinuria and an elevated creatinine level were
      both associated with an increased risk of death (for proteinuria: HR, 1.35
      [P=.04]; for creatinine: HR, 1.72 per decrease in the inverse unit [P=.02]).
      Among women initiating HAART, an elevated creatinine level remained associated
      with an increased risk of development of ADI (HR, 1.54 per decrease in the
      inverse unit; P=.03), and proteinuria and an elevated creatinine level were
      associated with an increased risk of death (for proteinuria: HR, 2.07 [P=.005];
      for creatinine: HR, 1.96 per decrease in the inverse unit [P=.04]). CONCLUSIONS:
      Proteinuria and an elevated creatinine level were associated with an increased
      risk of death and development of ADI. These associations may reflect the direct
      role of the kidney in modulating HIV disease, or they may act as markers of
      greater comorbidity.

PMID- 15486846
TI  - Safety and immunogenicity of an inactivated hepatitis A vaccine among HIV
      infected subjects.
AB  - BACKGROUND: Hepatitis A is a major health risk for many human immunodeficiency
      virus (HIV)-infected individuals. Vaccination is a potentially attractive measure
      to reduce the incidence of hepatitis A among this population, but data on its
      safety and immunogenicity are incomplete. METHODS: Ninety HIV-uninfected adults
      received an inactivated hepatitis A vaccine (VAQTA; Merck), and 90 HIV-infected
      subjects were randomized, in double-blind fashion, to receive either the vaccine
      or placebo. The HIV-infected subjects were stratified by CD4 cell count, with 45
      subjects having CD4 cell counts of > or =300 cells/mm3 and 45 subjects having CD4
      cell counts of <300 cells/mm3. Vaccine was given at weeks 0 and 24 of the
      study.Results. Seroconversion rates at week 28 of the study were 94% among the
      HIV-infected subjects and 100% among the HIV-uninfected control subjects. HIV
      infected subjects with CD4 cell counts of <300 cells/mm3 had a seroconversion
      rate of 87%, and HIV-infected subjects with CD4 cell counts of > or =300
      cells/mm3 had a seroconversion rate of 100%. The vaccine was generally well
      tolerated, and no adverse effect on either HIV load or CD4 cell count was found.
      CONCLUSION: Hepatitis A vaccine was both immunogenic and safe among HIV-infected
      subjects.

PMID- 15486847
TI  - Thrombotic complications in patients infected with HIV in the era of highly
      active antiretroviral therapy: a case series.
AB  - BACKGROUND: Recent reports suggest that patients infected with human
      immunodeficiency virus (HIV) may have an increased risk of developing thrombosis,
      but the etiology, risk factors, and clinical course remain largely undefined,
      with few descriptive case series. METHODS: We identified 30 patients from an HIV
      outpatient clinic (treatment population, 650 persons) who had had a total of 43
      venous or arterial thromboses during 1996-2002. Data pertaining to demographic
      characteristics, medical history, thrombosis presentation, and clinical outcomes
      were abstracted from patient medical records. RESULTS: The median patient age at
      the time of thrombosis was 43 years. Although the presence of persistent antibody
      to phospholipids was the most common abnormal finding in the laboratory,
      evaluation of thrombophilia, cases of low levels of proteins C and S and
      antithrombin III, and elevated levels of factor VIII and homocysteine were also
      identified. Seventy-seven percent of the patients smoked cigarettes, 57% had
      dyslipidemia, and 43% had a malignancy (most commonly Kaposi sarcoma). Although
      the Centers for Disease Control and Prevention (CDC) classification for 16
      patients (53%) was C3, most showed evidence of immune reconstitution (median CD4
      cell count, 290 cells/ mu L) and control of the virus (median HIV load, 2290
      copies/mL). Lower extremity, deep vein thrombosis and pulmonary emboli accounted
      for 66% of all thrombotic events. The median time to diagnosis of thrombosis was
      1 day (range, 3 h to 3 weeks). CONCLUSIONS: Patients in this series were
      characterized by a relatively young age at the time of thrombosis, a predominance
      of elevated levels of lipids, a history of malignancy, and an advanced CDC HIV
      classification but not by a low CD4 cell count or an elevated HIV load.

PMID- 15486848
TI  - Changes in weight and lean body mass during highly active antiretroviral therapy.
AB  - BACKGROUND: Few studies have prospectively evaluated the impact of highly active
      antiretroviral therapy (HAART) on body weight and lean body mass (LBM) or
      explored the impact of baseline immunologic or virological changes on these
      parameters. METHODS: Adult AIDS Clinical Trials Group (ACTG) protocol 892 was a
      prospective, 48-week, multisite observational study of body composition conducted
      during 1997-2000 among 224 antiretroviral-naive and antiretroviral-experienced
      subjects coenrolled into various adult ACTG antiretroviral studies. Assessments
      included human immunodeficiency virus type 1 (HIV-1) RNA load (by polymerase
      chain reaction); T lymphocyte subset analysis; Karnofsky score; height (baseline
      only); weight, LBM, and fat (by bioelectrical impedance analysis); and functional
      performance (by questionnaire). RESULTS: Overall, only modest median increases in
      body weight (1.9 kg) and LBM (0.6 kg) occurred after 16 weeks of therapy.
      Significantly greater median increases in body weight (2.1 vs. 0.5 kg; P=.045)
      occurred in subjects who achieved virological suppression (HIV-1 RNA load, <500
      copies/mL) at week 16 than in subjects who did not. Subjects who were
      antiretroviral naive at baseline gained more weight (median increase in body
      weight, 2.6 vs. 0.0 kg; P<.001) and LBM (1.0 vs. 0.1 kg; P=.002) after 16 weeks
      of treatment than did subjects who were antiretroviral experienced. Subjects with
      lower baseline CD4 cell counts (<200 cells/mm3) and subjects with higher baseline
      HIV-1 RNA loads (> or =100,000 copies/mL) were more likely to show increases in
      LBM of >1.5 kg (P=.013 and P=.005, respectively). CONCLUSIONS: HAART had modestly
      favorable effects on body composition, particularly in patients with greater
      pretreatment immunocompromise and virological compromise. The difference between
      antiretroviral-naive and antiretroviral-experienced subjects with regard to the
      ability to achieve increased body weight and LBM requires more study.

PMID- 15486849
TI  - Evidence for differences in the sexual transmission efficiency of HIV strains
      with distinct drug resistance genotypes.
AB  - BACKGROUND: The transmission of drug-resistant human immunodeficiency virus type
      1 (HIV-1) is a matter of major concern, because it could compromise the response
      to antiretroviral therapy. MATERIAL AND METHODS: From 1997 through 2003,
      genotypic drug resistance profiles in 89 patients with recent HIV-1
      seroconversion were compared in a case-control study with HIV-1 genotypes
      obtained from 520 subjects identified at Hospital Carlos III in Madrid, Spain, as
      "potential transmitters" of drug-resistant virus. This group consisted of HIV
      infected patients experiencing virologic failure of antiretroviral therapy.
      RESULTS: Drug resistance mutations were recognized in 15 (16.8%) of 89 patients
      with recent HIV-1 seroconversion (the seroconverter group), providing resistance
      to nucleoside reverse-transcriptase inhibitors (NRTIs) in 14.6%, nonnucleoside
      reverse-transcriptase inhibitors (NNRTIs) in 3.4%, and protease inhibitors (PIs)
      in 3.4%. Among individuals who were potential transmitters of HIV-1 (the
      potential transmitter group), drug resistance mutations were found in 80%,
      providing resistance to NRTIs in 73.7%, NNRTIs in 36.4%, and PIs in 38.7%. The
      estimated ratio of individuals with recent HIV-1 seroconversion to potential
      transmitters for drug-resistance genotypes was 0.23 for resistance to NRTIs, 0.09
      for resistance to NNRTIs, and 0.09 for resistance to PIs. For specific resistance
      mutations, the ratio of individuals with recent HIV-1 seroconversion to potential
      transmitters was 0.18 for 41L, 0.20 for 215Y/F (including revertants), 0.06 for
      184V, 0.04 for 103N, and 0.14 for 181C when considering drug resistance mutations
      in the reverse transcriptase (RT) gene; the ratio was 0.12 for 46L, 0.06 for
      82A/T/S, and 0.08 for 90L, when examining PI resistance mutations. CONCLUSION:
      Strains of HIV with some drug resistance genotypes (41L, 215Y/F, and 181C in the
      RT gene and 46L in the protease gene) may be more efficiently transmitted than
      strains with other drug resistance mutations (184V and 103N in the RT gene and
      82A/S/T and 90M in the protease gene).

PMID- 15486851
TI  - How does a patient maximally benefit from anti-infective chemotherapy?

PMID- 15486850
TI  - Adverse reactions to voriconazole.
AB  - Voriconazole is a new antifungal agent effective in the treatment of invasive
      aspergillosis. Interpatient variation in plasma concentrations is considerable-
      more than 100-fold. We describe 3 patients with diverse manifestations of
      toxicity (e.g., hallucinations, hypoglycemia, electrolyte disturbance, and
      pneumonitis) possibly attributable to high voriconazole concentrations.
      Measurement of plasma concentrations could be helpful in optimizing voriconazole
      dosages.

PMID- 15486852
TI  - Factors associated with psychosis among patients with severe acute respiratory
      syndrome: a case-control study.
AB  - We observed that a number of patients with severe acute respiratory syndrome
      (SARS) developed affective psychosis during the acute phase of their illness. We
      reviewed all SARS-related psychiatric consultations in Hong Kong and investigated
      the risk factors for psychosis among patients with SARS in a matched case-control
      study. Patients with SARS-related psychosis received higher total doses of
      steroids and had higher rates of family history of psychiatric illness. The
      findings of the present study suggest that steroid toxicity, personal
      vulnerability, and, probably, psychosocial stressors jointly contributed to the
      development of psychosis in patients with SARS.

PMID- 15486853
TI  - Spondylitis and arthritis due to Mycoplasma hominis: the case for awareness in
      undefined pleuropneumonia.

PMID- 15486854
TI  - Chlamydia pneumoniae and asthma in children: diagnostic issues.

PMID- 15486856
TI  - Failure of caspofungin to treat brain abscesses secondary to Candida albicans
      prosthetic valve endocarditis.

PMID- 15486857
TI  - Granulomatous infections due to tumor necrosis factor blockade: correction.

PMID- 15486858
TI  - Inconsistencies in reporting of granulomatous infectious diseases associated with
      infliximab and etanercept.

PMID- 15486859
TI  - Tuberculosis cases associated with infliximab and etanercept.

PMID- 15486861
TI  - Clinical hyperthyroidism in Chinese patients with stable HIV disease.

PMID- 15486862
TI  - Correction regarding adalimumab labelling.

PMID- 15486863
TI  - Testing for HIV to destigmatize and improve diagnosis of HIV infection.

PMID- 15486864
TI  - The diagnostic usefulness of cerebrospinal fluid lactic acid levels in central
      nervous system infections.

PMID- 15486865
TI  - Successful discontinuation of high-dose fluconazole for Histoplasma capsulatum
      meningitis in an AIDS patient after sustained immune reconstitution.

PMID- 15486867
TI  - The Dialysis Outcomes and Practice Patterns Study (DOPPS) and the Kidney Disease
      Outcomes Quality Initiative (K/DOQI): a cooperative initiative to improve
      outcomes for hemodialysis patients worldwide.
AB  - Two initiatives were launched in the closing years of the past century with the
      goal of improving the treatment outcomes of patients with kidney failure: the
      Kidney Disease Outcomes Quality Initiative, which formed expert panels to develop
      evidence-based clinical practice guidelines, and the Dialysis Outcomes and
      Practice Patterns Study (DOPPS), which now gathers data on practice patterns in
      dialysis facilities in 12 countries, including the United States. Recently, the
      Kidney Disease: Improving Global Outcomes (KDIGO) program was established to
      promote worldwide coordination and integration of initiatives to develop and
      implement clinical practice guidelines and provides new opportunities of
      cooperation with the international scope of the DOPPS. Collaboration between the
      DOPPS and KDIGO will lead to broader dissemination of relevant information to
      nephrologists, health care providers, and patients. Linking the DOPPS scope of
      work with the KDIGO goals will help develop continuous quality improvement
      programs and the provision of direct feedback to participating dialysis centers
      throughout the world. This will establish an essential component in the
      translation to clinical practice of evidence-based guidelines worldwide.

PMID- 15486868
TI  - The Dialysis Outcomes and Practice Patterns Study (DOPPS): design, data elements,
      and methodology.
AB  - The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective,
      observational study designed to elucidate aspects of hemodialysis practice that
      are associated with the best outcomes for hemodialysis patients. In DOPPS I, 308
      hemodialysis units from 7 countries participated, including 145 facilities from
      the United States (1996-2001), 62 facilities from Japan (1999-2001), and 101
      facilities from France, Germany, Italy, Spain, and the United Kingdom (all 1998
      2000). DOPPS II (2002-2004) has included 320 hemodialysis units and more than
      12,400 hemodialysis patients from the 7 DOPPS I countries as well as Australia,
      Belgium, Canada, New Zealand, and Sweden. Dialysis units are chosen via a
      stratified random selection procedure to provide proportional sampling by region
      and type of facility within each country. In DOPPS I and II, longitudinal data
      have been collected from both a prevalent (cross-sectional) patient sample and an
      incident patient sample. Data have also been collected on numerous facility
      practice patterns. Most DOPPS analyses incorporate both facility- and patient
      level data in regression-based analyses to investigate predictors of survival,
      hospitalization, quality of life, vascular access type, and other outcomes. DOPPS
      longitudinal data also help identify trends in subject characteristics, practice
      indicators, medication use, and outcomes. The DOPPS remains a unique source of
      data on hemodialysis patients and facilities. It continues to refine its methods
      of data collection and analysis with the goal of improving hemodialysis practice
      and end-stage renal disease patient lives worldwide.

PMID- 15486869
TI  - Mortality among hemodialysis patients in Europe, Japan, and the United States:
      case-mix effects.
AB  - BACKGROUND: The Dialysis Outcomes and Practice Patterns Study is well suited to
      identify case-mix effects, given its extensive data set. The data set was used to
      examine the influence of case-mix variables on mortality and the extent to which
      these variables account for differences in mortality across regions, as well as
      the prevalence and incidence of hepatitis B and hepatitis C. METHODS: Demographic
      and comorbid disease features were determined for 8,615 patients internationally;
      mortality was recorded for this cohort, plus replacement patients (total n =
      16,720), from 1996 to 2002. Mortality was associated with increasing age,
      nonblack race, coronary artery disease, congestive heart failure, other cardiac
      disease, diabetes mellitus, peripheral vascular disease, cerebrovascular disease,
      absence of hypertension, lung disease, cancer, human immunodeficiency virus
      infection, gastrointestinal bleeding, neurologic disease, psychiatric disease,
      cellulitis/gangrene, hepatitis C, and smoking. RESULTS: US patients were slightly
      older than those in Europe or Japan and had the highest prevalence of diabetes,
      coronary artery disease, congestive heart failure, peripheral vascular disease,
      and cerebrovascular disease. CONCLUSION: Upon adjusting for case-mix to assess
      mortality across facilities, it was found that regional differences in mortality
      (highest in the United States and lowest in Japan) and differences across
      facilities within nations remain after such corrections. It is likely that
      practice patterns account for some of this variation. Prevalence of hepatitis B
      virus (HBV) across facilities increased as the number of dialyzing patients per
      facility increased; risk of HBV seroconversion decreased among facilities using
      protocols for treatment of patients with HBV infection. Greater employment of
      staff with at least 2 years of formal nursing training was associated with lower
      prevalence of hepatitis C virus infection and lower seroconversion risk.

PMID- 15486870
TI  - Vascular access results from the Dialysis Outcomes and Practice Patterns Study
      (DOPPS): performance against Kidney Disease Outcomes Quality Initiative (K/DOQI)
      Clinical Practice Guidelines.
AB  - BACKGROUND: The Kidney Disease Outcomes Quality Initiative Guidelines for
      Vascular Access in hemodialysis patients recommend native arteriovenous (AV)
      fistulae over AV grafts or catheters for permanent vascular access. They
      recommend letting fistulae mature > or =1 month before cannulation. METHODS: The
      Dialysis Outcomes and Practice Patterns Study (DOPPS) provides an unparalleled
      means to examine vascular access practice patterns and guidelines
      internationally, with particular attention to associations with mortality risk.
      RESULTS: Most patients in Europe and Japan dialyze through AV fistulae and very
      few use AV grafts; in the United States, more patients use grafts than fistulae.
      Patients who receive nephrologic care for over 30 days before starting dialysis
      have significantly higher chances of commencing via AV fistula. Medical directors
      of dialysis facilities in the United States commonly prefer grafts; in Europe and
      Japan, most prefer fistulae. In the United States, there is a relatively long
      average time between fistula creation and cannulation but significantly worse
      fistula survival than that seen in Europe. Tunneled catheters pose a higher
      mortality risk than permanent accesses and are associated with increased risk of
      failure of a subsequent fistula. The percentage of prevalent patients in the
      DOPPS countries using catheters has increased in recent years. DOPPS data suggest
      that performance in some countries falls short of practices achieved in other
      countries. AV fistula use is low in the United States but has been improving. The
      trend of increasing use of catheters in most countries is discouraging.
      CONCLUSION: The DOPPS will continue to monitor practice trends and explore
      whether greater application of guidelines will lead to fewer access complications
      and improved longevity for hemodialysis patients.

PMID- 15486871
TI  - Anemia management for hemodialysis patients: Kidney Disease Outcomes Quality
      Initiative (K/DOQI) guidelines and Dialysis Outcomes and Practice Patterns Study
      (DOPPS) findings.
AB  - BACKGROUND: After recombinant human erythropoietin was introduced into routine
      nephrologic practice, specific clinical guidelines were developed to optimize the
      quality of anemia management for patients with chronic kidney disease. METHODS:
      The Dialysis Outcomes and Practice Patterns Study (DOPPS), an international
      investigation providing patient- and facility-level data on hemodialysis
      practice, was developed to provide information on various aspects of current
      practices in hemodialysis management, including treatment of renal anemia.
      RESULTS: Hemoglobin concentration is strongly associated with both morbidity and
      mortality in hemodialysis patients. Although some improvements can be documented
      in anemia management practices in the years after the publication of
      international guidelines, wide variations in anemia management are still observed
      among countries. CONCLUSION: Many efforts are still needed to allow a greater
      proportion of patients to reach the recommended hemoglobin concentrations.
      Significantly improved outcomes may therefore be expected by a more widespread
      reaching of the recommended hemoglobin levels. The results of the DOPPS point to
      the difficulties in implementing clinical guidelines in the everyday management
      of individual patients. In specific circumstances, a well-designed observational
      study may offer credible information and serve as a basic instrument for
      monitoring the implementation of clinical guidelines in typical clinical
      practice.

PMID- 15486872
TI  - Magnitude and impact of abnormal mineral metabolism in hemodialysis patients in
      the Dialysis Outcomes and Practice Patterns Study (DOPPS).
AB  - BACKGROUND: Mineral metabolism has emerged as an important predictor of morbidity
      and mortality in dialysis patients, independent of bone and muscle concerns.
      Several expert panels have issued management guidelines for mineral metabolism.
      METHODS: The state of mineral metabolism (serum parathyroid hormone [PTH],
      phosphorus, calcium, and calcium-phosphorus product) was described for
      representative samples of patients and facilities from 7 countries (France,
      Germany, Italy, Japan, Spain, United Kingdom, and United States) participating in
      the Dialysis Outcomes and Practice Patterns Study (DOPPS I, 1996-2001; DOPPS II,
      2002-2004). RESULTS: A relatively modest percentage of patients fell within the
      guideline range for PTH (21.4% in DOPPS I, 26.2% in DOPPS II), serum phosphorus
      (40.8%, 44.4%), albumin-corrected serum calcium (40.5%, 42.5%), and calcium
      phosphorus product (56.6%, 61.4%). Results were not dramatically different across
      countries. The majority of patients not within guideline ranges had high serum
      levels of phosphorus (51.6% in DOPPS I, 46.7% in DOPPS II), calcium (50.1%,
      48.6%), and calcium-phosphorus product (43.4%, 38.6%) and low (<150 pg/mL)
      concentrations of PTH (52.9%, 47.5%). It was rare for patients to fall within
      recommended ranges for all indicators of mineral metabolism; 23% to 28% fell
      within guideline for at least 3 measures and only 4.6% to 5.5% of patients were
      within range for all 4. The risks of all-cause and cardiovascular mortality were
      directly and independently associated with each of the 4 indicators. CONCLUSION:
      The DOPPS provides a useful comparison benchmark for the state of mineral
      metabolism management of patients with kidney disease; it also affirms the
      association between mineral metabolism and important patient outcomes.

PMID- 15486873
TI  - Kidney Disease Outcomes Quality Initiative (K/DOQI) and the Dialysis Outcomes and
      Practice Patterns Study (DOPPS): nutrition guidelines, indicators, and practices.
AB  - BACKGROUND: Nutritional markers are important predictors of morbidity and
      mortality in dialysis patients. The Clinical Practice Guidelines for Nutrition in
      Chronic Renal Failure provides guidelines for assessing nutritional status that
      were evaluated using data from the Dialysis Outcomes and Practice Patterns Study
      (DOPPS). METHODS: The level of various nutritional markers (serum albumin,
      modified subjective global assessment, serum creatinine, normalized protein
      catabolic rate [nPCR], and body mass index) were described for representative
      samples of patients and facilities from 7 countries (France, Germany, Italy,
      Spain, Japan, United Kingdom, and United States) participating in the DOPPS.
      RESULTS: A strong inverse association was observed between mortality and serum
      albumin, with a mortality risk 1.38 times higher for patients with serum albumin
      concentration less than 3.5 g/dL (35 g/L). There were significant differences by
      country in the proportion of moderately and severely malnourished patients as
      determined by the modified subjective global assessment score. In the US sample,
      severely and moderately malnourished patients had a higher mortality risk
      compared with those not malnourished, 33% and 5% higher, respectively. An inverse
      relationship exists between serum creatinine concentration and mortality, with a
      mortality risk 60% to 70% higher in the lowest quartile group compared with the
      highest quartile group in Europe and the United States. Levels of nPCR varied
      significantly between European countries, and there was no association between
      mortality and nPCR in US data. After adjustment for demographic and comorbidity
      factors, the mortality risk decreased as body mass index increased in both US and
      European samples. CONCLUSION: DOPPS data highlight the importance of routine
      assessment of nutritional status, using multiple parameters, in clinical practice
      to improve patient care.

PMID- 15486874
TI  - Dose of dialysis: key lessons from major observational studies and clinical
      trials.
AB  - Analyses based on the National Cooperative Dialysis Study (NCDS) provided the
      impetus for routine quantification of delivered dialysis dose in hemodialysis
      practice throughout the world, by suggesting minimum targets for small solute
      (urea) clearance. Morbidity and mortality in dialysis populations remain high
      despite many technological advances in dialysis delivery. A number of
      observational studies reported association between higher dose of dialysis as
      measured by Kt/V urea or urea reduction ratio with lower mortality risk. During
      the 1990s, a steady increase in dialysis dose and a modest reduction in mortality
      on dialysis were observed. However, observational studies only reveal
      associations and are limited by selection bias and confounding. The Kidney
      Disease Outcomes Quality Initiative guidelines on dialysis adequacy are based on
      results of observational studies and expert opinion. Since the NCDS, the HEMO
      Study was the first major randomized clinical trial designed to study the effect
      of dose of dialysis and dialyzer flux on patient outcomes. Despite adequate
      separation of dose and flux, however, results of the trial did not prove a
      beneficial effect of higher dose. The Dialysis Outcomes and Practice Patterns
      Study (DOPPS), in a major international effort designed to examine the effect of
      practice patterns on outcomes, has made significant contributions to the topic of
      dialysis dose. The following review critically examines data from observational
      studies, including the DOPPS, and from the HEMO Study, emphasizing important
      lessons from both, and discusses future paradigms for achieving dialysis adequacy
      to improve patient outcomes.

PMID- 15486875
TI  - Health-related quality of life in the Dialysis Outcomes and Practice Patterns
      Study (DOPPS).
AB  - BACKGROUND: Health-related quality of life (HRQOL), a validated system of
      measuring patients' physical, mental, and social well-being, can be of particular
      use in populations with chronic conditions, such as end-stage renal disease
      (ESRD). METHODS: The Dialysis Outcomes and Practice Patterns Study (DOPPS) has
      used the Kidney Disease Quality of Life Short Form (KDQOL-SF) to measure ESRD
      patients' self-assessment of functioning and well-being, as measured by 3
      component scores: physical component summary (PCS, 4 subscales), mental component
      summary (4 subscales), and kidney disease component summary (11 subscales).
      Several DOPPS studies examined HRQOL's associations with mortality and
      hospitalization by country, ethnicity (United States only), and in comparison
      with serum albumin levels; international variations in HRQOL of ESRD patients
      were also evaluated. RESULTS: Lower scores for all 3 summary scores were strongly
      associated with higher risk of death and hospitalization; these measures,
      especially PCS, may better identify patients at risk for death and
      hospitalization than serum albumin level. Japanese patients reported a greater
      burden of kidney disease but higher physical functioning than patients in Europe
      or the United States; many other significant regional differences in HRQOL were
      found. In the United States, all summary scores were significantly associated
      with mortality risk, regardless of ethnicity. Compared with whites, blacks had
      higher scores for all 3 summary scores, Asians and Hispanics had higher PCS
      scores, and Native Americans had lower mental component summary scores.
      CONCLUSION: Among ESRD patients, HRQOL displays an important predictive power for
      adverse events. Identifying effective interventions to improve the HRQOL of
      patients with ESRD should be viewed as a valued health care goal.

PMID- 15486876
TI  - Dialysis Outcomes and Practice Patterns Study (DOPPS) data on medications in
      hemodialysis patients.
AB  - BACKGROUND: Medications affect many measures of hemodialysis patients' well
      being. METHODS: The Dialysis Outcomes and Practice Patterns Study (DOPPS) has
      evaluated the use of hydroxymethyl glutaryl coenzyme A reductase inhibitors
      (statins), analgesics, antidepressants, and multivitamins. Additionally, DOPPS
      has reported on the associations between vascular access outcomes and related
      medications. RESULTS: Prescription of statins varied widely across countries,
      with the highest use in the United States. Patients prescribed statins had lower
      risk of cardiac and noncardiac causes of mortality than those who were not
      prescribed statins. DOPPS data also show that statins are underprescribed
      relative to recent Kidney Disease Outcomes Quality Initiative guidelines. No
      guidelines have been established for analgesic use, but high pain levels self
      reported by hemodialysis patients suggest opportunities for improved pain
      management strategies. Guidelines for analgesic use in dialysis patients may help
      balance improved quality of life against potential side effects of analgesics.
      Medical and patient questionnaires show that depression in hemodialysis patients
      is common, frequently underdiagnosed, usually untreated, and associated with
      increased rates of mortality and hospitalization. Calcium channel blockers were
      associated with improved primary graft patency, aspirin with improved secondary
      graft patency, and angiotensin-converting enzyme inhibitors with improved
      secondary fistula patency. All 3 medications were associated with significantly
      decreased relative risk for access failure. There is large country variation in
      multivitamin use, with significantly higher use in the United States compared
      with Europe and Japan. Patients taking multivitamins had lower mortality risk
      than patients not taking multivitamins. CONCLUSION: DOPPS findings on medications
      indicate that prospective trials are needed before guidelines can be developed
      for appropriate medication use in these different therapeutic categories.

PMID- 15486877
TI  - Inflammatory myofibroblastic tumor (inflammatory pseudotumor) of the neck
      infiltrating the trachea.
AB  - Inflammatory myofibroblastic tumor (IMT), popularly known as inflammatory
      pseudotumor, is a slow growing quasi-neoplastic lesion with a distinct histologic
      appearance and benign clinical course. A case of a neck IMT with infiltration
      into the trachea causing asthmalike symptoms in a 12-year-old girl is described.
      Both tracheal and neck IMT have been described, but no other case has displayed
      this infiltration. A review of the pertinent literature and the etiology,
      diagnosis, treatment, and outcomes of this tumor are discussed. It is important
      to consider IMT in a differential diagnosis because it can be easily misdiagnosed
      as a malignancy. A surgeon must not perform radical surgery, radiation, or
      chemotherapy until a final pathologic diagnosis is made because of the nature of
      this lesion.

PMID- 15486878
TI  - Camel bite: an unusual type of head injury in an infant.
AB  - Small children are predisposed for animal bite wounds in the craniofacial region,
      because the likelihood of sustaining trunk and extremity injuries increases with
      height. The clinical picture of animal bite wounds is highly variable. Depending
      on the dental anatomy of the biting animal, such wounds may range from sharp
      stitch wounds to extensive lacerations with or without tissue loss. The ears and
      nose are injured most often because of their exposed location. Nevertheless,
      depressed skull fractures with injury to the dura and to the brain parenchyma are
      extremely rare. This case presentation describes the rare case of a
      craniocerebral camel bite wound (Lackmann stage IV B) in a 3-year-old girl that
      required immediate neurosurgical management. The neurosurgical management, choice
      of antibiotic, postoperative treatment, and clinical course are discussed, and
      background information on camel bite injuries is given.

PMID- 15486879
TI  - Multilocular cystic renal cell carcinoma in a child.
AB  - Multilocular cystic renal cell carcinoma is an extremely rare condition in adults
      with no previous case reports in the pediatric age group. The authors report on
      an 8-year-old girl who underwent nephrectomy for a right-sided renal cystic
      disease because of extensive involvement of the kidney. Subsequent
      histopathologic examination findings showed presence of renal cell carcinoma in
      all the cysts. Awareness of this malignancy in a child is extremely important in
      the background of recent reports advocating conservative wait and watch
      management in unilateral renal cystic disease, which has similar clinical and
      imaging findings.

PMID- 15486880
TI  - Occult, life-threatening, cardial tumor in syndactylism in Gorlin Goltz syndrome.
AB  - Pediatric, orthopedic, plastic, and hand surgeons perform the surgical correction
      of syndactylism. It is sometimes forgotten, however, that syndactylism can be
      part of a syndrome. The components of such a syndrome can each be life
      threatening. A 7-month-old boy was hospitalized for correction of cutaneous
      syndactylism. The mother claimed that, with the exception of the syndactylism,
      her son was healthy. However, review of the admission documents found that the
      family physician suspected Gorlin Goltz syndrome. A preoperative echocardiography
      showed 3.9-cm intramural tumor in the wall of the left ventricle.
      Electrocardiography documented ventricular tachycardia. Because of the danger of
      life-threatening malignant ventricular tachycardia, the tumor was resected.
      Before the resection, cardiac transplantation was considered because of the size
      of the tumor. Histologic examination found a fibroma. When observing
      syndactylism, one must always be aware of the possibility of a syndromic disease.
      It is particularly important that screening investigations, including
      electrocardiography and echocardiography, are performed before surgical
      treatment.

PMID- 15486881
TI  - Traumatic handlebar hernia: a rare abdominal wall hernia.
AB  - Traumatic abdominal wall herniation (TAWH) caused by direct trauma from bicycle
      handlebars are rare. There are only 21 reported cases of handlebar hernias. An 11
      year-old boy presented to the emergency room soon after falling from his bicycle
      and hitting his right lower quadrant on the handlebars. The patient's vital signs
      and initial laboratory studies were normal. Physical exam showed a soft tissue
      bulge in the right lower quadrant with superficial ecchymosis and tenderness to
      palpation. Computed tomography showed intestinal loops protruding through a
      defect in the abdominal wall into the subcutaneous space. Surgical exploration
      found a defect throughout his entire abdominal wall including the fascia,
      muscular layers, and peritoneum, with bowel protruding into the subcutaneous
      space. The defect was repaired in layers, and the child's postoperative course
      was unevenful. The authors recommend a high level of clinical suspicion for TAWH
      in all patients with traumatic abdominal wall injuries. Definitive treatment
      includes surgical exploration with primary repair of all tissue layers of the
      abdominal wall.

PMID- 15486882
TI  - Left colon stenosis caused by tuberculosis.
AB  - The authors present a case of intestinal tuberculosis affecting exclusively the
      left colon causing severe undernourishment, abdominal pain, and bowel obstruction
      with a sealed colonic fistula in a 10-year-old child. These clinical
      characteristics and difficulties led to a diagnosis of intestinal tuberculosis in
      childhood. Intestinal tuberculosis affecting exclusively the colon is very rare,
      and differential diagnosis with Crohn's disease is difficult. Surgical
      complications are frequent, especially intestinal obstruction, and can be treated
      in most cases by resection of the affected segment and primary anastomosis.

PMID- 15486883
TI  - Laparoscopic excision of a gastric duplication cyst detected on antenatal
      ultrasound scan.
AB  - The authors report a gastric duplication cyst detected antenatally and its
      subsequent laparoscopic removal at 2 months of age. Before birth, a cystic mass
      was detected behind the stomach on fetal ultrasound scan (US). After birth, an
      US, barium meal, nuclide scan, and cervical and thoracic vertebral x-rays
      suggested that the most probably diagnosis was a gastric duplication cyst. At 2
      months of age, laparoscopic removal of the cyst was performed with closure of the
      muscle defect in the stomach wall. The patient was discharged 4 days later,
      feeding normally. Histology findings confirmed the diagnosis of a gastric
      duplication cyst. After the antenatal detection of a cyst behind the stomach, the
      laparoscopic removal of this gastric duplication in a 2 month old was
      accomplished without complications. This appears to be the first reported case
      using this type of procedure in an infant.

PMID- 15486884
TI  - Hirschsprung's disease--a complicated therapeutic problem: some thoughts and
      solutions based on data and personal experience over 56 years.

PMID- 15486887
TI  - Persistent obstructive symptoms after surgery for Hirschsprung's disease:
      development of a diagnostic and therapeutic algorithm.
AB  - BACKGROUND: Although most children with Hirschsprung's disease (HD) do well after
      pull-through surgery, some continue to have persistent obstructive symptoms that
      may lead to significant morbidity. The author's goal was to develop an organized
      algorithm for the workup and ultimate management of these symptoms. METHODS: All
      children referred to the author with severe obstructive symptoms after a pull
      through for HD were evaluated using an algorithm based on 5 potential etiologies,
      and appropriate therapeutic interventions were instituted. RESULTS: A total of 49
      children were evaluated over 7 years. Mechanical obstruction was found using
      rectal examination and barium enema in 7, of which, 2 had resection of a Duhamel
      spur, and 5 had a repeat pull-through (after failed dilatation). Rectal biopsy
      results showed aganglionosis in 10, of whom, 8 underwent repeat pull-through, and
      2 refused further surgery. Abnormal intestinal motility or intestinal neuronal
      dysplasia was found proximal to the aganglionic segment in 10 children using
      colonic and small bowel manometry or laparoscopic biopsies; 4 of these had
      additional colon resected and repeat pull-through, and 6 were treated with a
      bowel management routine, cecostomy, or stoma formation. Internal sphincter
      achalasia was felt to be the primary cause of symptoms in 14, and all were
      treated with intrasphincteric botulinum toxin. Eight were found not to fall into
      any of the above groups and were treated medically for presumed functional
      megacolon; 2 of these ultimately had a colostomy. CONCLUSIONS: An organized
      approach to the diagnosis and management of obstructive symptoms in a child after
      a pull-through for HD permits accurate diagnosis and effective treatment in the
      majority of cases.

PMID- 15486888
TI  - Robot-enhanced fetoscopic surgery.
AB  - BACKGROUND: Fetoscopic surgery carries with it less maternal morbidity than open
      fetal surgery. Robotic surgery facilitates endoscopic surgery through tremor
      filtration, motion scaling, indexed movement, articulation, and improved
      ergonomics. The goal of the authors was to explore using a robotic surgery
      platform in a fetal animal model. METHODS: Using the Zeus Robotic Surgery System
      (Computer Motion, Santa Barbara, CA), fetoscopic surgery in pregnant sheep was
      performed using a variety of techniques: uterus exteriorized or totally
      percutaneous and with liquid or gas insufflation. Using the percutaneous
      technique and gas insufflation, the authors created and sutured fetal skin and
      fascial defects. The ewes were recovered and killed 2 weeks postoperatively, and
      autopsies were performed on them and their fetuses. RESULTS: In the exteriorized
      uterus model, instrument movement was unpredictable and fluid leaked. In the
      fluid environment, clouding of the visual field and difficulty in immobilizing
      the fetus were major difficulties. In the survival model, 4 of the 6 fetuses
      survived to autopsy at 2 weeks and showed good healing grossly and
      histologically. CONCLUSIONS: The Zeus Robotic Surgery System can be used for
      fetoscopic surgery in a sheep model. The percutaneous approach with a nitrous
      oxide environment is the most effective. Advantages of robotic surgery may be
      applicable in fetoscopic surgery, but further work in a primate model is
      required.

PMID- 15486889
TI  - The treatment of high and intermediate anorectal malformations: one stage or
      three procedures?
AB  - BACKGROUND/PURPOSE: The aim of this study was to examine the safety, feasibility,
      and the long-term outcome of complete 1-stage repair of high and intermediate
      anorectal malformation using posterior sagittal anorectoplasty (PSARP) in a
      neonate. METHODS: One hundred thirteen patients with high-type and intermediate
      type anorectal malformations (ARM) underwent follow-up. Of 113 cases, 48 cases
      entailed a divided colostomy, definitive operation, and colostomy closure (group
      I); the other 65 patients underwent 1-stage PSARP (group II). Anorectal function
      was measured by the modified Wingspread scoring, including "excellent," "good,"
      "fair," and "poor." In barium enema studies, anorectal angulation was judged as
      "clear," "unclear," and "not present," and leakage of barium was observed in the
      meantime. For anorectal manometric studies, anal resting pressure (ARP), anal
      squeezing pressure (ASP), and positive anorectal reflex (PAR) were measured.
      RESULTS: In group I, the rate of excellent and good scores was 58.3% (28 of 48).
      In the barium enema examination, 85.4% (41 of 48) was clear and 14.6%(7 of 48)
      unclear or not present. The rate of barium leakage was 10.4% (5 of 48). In group
      II, the rate of excellent and good was 53.8% (35 of 65). Anorectal angulations
      were clear in 83.1% of patients (54 of 65). Barium leakage happened in 7.69% of
      patients (5 of 65). Early operative complications occurred in 56.3% (27 of 48) of
      patients in group I and 29.2% (19 of 65) in group II. The incidence of colostomy
      complications in group I was 39.6% (19 of 48). Soiling and constipation were the
      major complications after the PSARP operation. The respective rates of
      constipation in the 2 groups were 47.9% (23 of 48) and 44.6% (29 of 65), and the
      respective rates of soiling were 47.9% (23 of 48) and 50.8% (33 of 65). There was
      no significant difference in the mean ARP between the 2 groups. CONCLUSIONS: The
      1-stage PSARP procedure in the neonate not only achieves the same long-term
      outcome as the conventional PSARP procedure but also involves fewer short-term
      complications. Complete 1-stage repair using the PSARP to treat high-type and
      intermediate-type anorectal malformations is safe and feasible.

PMID- 15486890
TI  - Clinical policy: evidence-based approach to pharmacologic agents used in
      pediatric sedation and analgesia in the emergency department.

PMID- 15486891
TI  - Mesh wrap in severe pediatric liver trauma.
AB  - PURPOSE: This study reviews the authors' experience in treating severe pediatric
      liver injuries with absorbable mesh wrapping. The authors found this relatively
      new therapeutic method very useful in selected cases, although its use is not
      very common in children. The authors analyze the indication describe some
      technical aspects, and discuss the advantages and the pitfalls of the method.
      METHODS: In a 10-year period between 1990 and 2000, 181 children were admitted to
      Hillel-Yaffe Medical Center with blunt hepatic trauma. A total of 132 children
      were treated conservatively, and 49 (27%) were operated on. The operated group
      included 35 cases of isolated liver injuries and 14 cases of additional
      intraabdominal injuries. Thirty-four children were operated on between 1990 and
      1995 (36% of 96 children), whereas between 1995 and 2000, 15 children were
      operated on (17% of 85 children), including 4 children aged 18 months to 15 years
      with massive liver bleeding who were treated with mesh wrap technique. The
      retrospective analysis of these 4 cases indicates a progressive policy in the
      recognition of cases suitable for mesh wrapping and gallbladder conservation.
      RESULTS: The perihepatic mesh wrap technique controlled the bleeding in all
      children. In 3 of them the right lobe was wrapped, and, in 1 case, total liver
      wrapping was performed. Hepatic enzymes and bilirubin levels were elevated in the
      first 3 to 7 days and declined gradually to normal levels. The perihepatic mesh
      was not an obstacle to a transcutaneous drainage of an intrahepatic biloma. All 4
      children returned to normal physical activities. CONCLUSIONS: Liver mesh wrap is
      a simple, effective, and rapid way to obtain hemostasis and to conserve
      parenchyma in severe traumatized liver. The decision to wrap the liver should be
      done early to prevent acidosis and hypothermia. Cholecystectomy is not an
      integral part of the procedure in children. The morbidity is low, and most of the
      complications can be treated nonsurgically.

PMID- 15486892
TI  - Potential diagnostic value of pancreatic isoamylases for pancreaticobiliary
      maljunction with mild biliary dilatation in patients and a porcine model.
AB  - PURPOSE: The aim of this study was to evaluate the diagnostic value of serum
      pancreatic isoamylases for pancreaticobiliary maljunction (PBM) with mild biliary
      dilatation. METHODS: Serum and bile from 8 children with PBM and mild biliary
      dilatation (6 to 11 mm in diameter) and 4 young pigs with an anastomosis
      constructed between an isolated pancreas-duodenal segment and the gallbladder
      were studied for pancreatic isoamylases. Using an electrophoretic technique, the
      assay of pancreatic isoamylases was expressed by peak appearance rate (PAR).
      Serum from 20 healthy children served as normal controls. RESULTS: In the serum
      of the patients, preoperatively there were 5 pancreatic peaks with PAR as
      follows: P1, 100%; P2, 100%; P3, 100%; P4, 100%; and P5, 66.7%. These abnormal
      pancreatic isoamylases disappeared 2 weeks after operative treatment. In normal
      controls, there were only P1 (PAR, 40%) and P2 (PAR, 100%). Mild cylindrical
      dilatation (6 to 8 mm in diameter) of the common bile duct developed in the
      porcine PBM model. There were P1 (PAR, 100%) and P2 (PAR, 100%) in the porcine
      serum preoperatively. Thirty days and 60 days after establishing the model, there
      appeared in the serum 6 pancreatic peaks with PAR as follows: P1, 100%; P2, 100%;
      P3, 75%; P4, 100%; P5, 100%, and P6; 75%. The bile patterns of pancreatic
      isoenzymes in the patients and pigs were similar to those in serum. CONCLUSIONS:
      Abnormal pancreatic isoamylases are characteristically present in the serum from
      both children and a porcine model of PBM and mild biliary dilatation. Assay for
      these abnormalities is promising to recognize this subset of patients in whom
      diagnosis remains a challenge.

PMID- 15486893
TI  - Gastrointestinal stromal tumors arising from the stomach: a report of three
      children.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GIST) are a unique subset of
      intestinal mesenchymal tumors that behave in an aggressive fashion. They have
      been commonly described in adults but have been rarely observed in children.
      METHODS: The authors review the presentation, diagnostic workup, operative
      records, pathologic specimens, and outcomes of 3 children with GISTs that
      originated from the stomach. RESULTS: All 3 children presented after upper
      gastrointestinal bleeding from the gastric tumor. The first was a 10-year-old
      girl who underwent partial gastrectomy but had recurrence 8 years later requiring
      a second resection. She subsequently had a hepatic metastasis 8 years later
      requiring a third resection. The second patient was a 9-year-old girl who had an
      antrectomy with a Bilroth I reconstruction and was noted to have a synchronous
      liver metastasis that was also resected. Despite Imatinib Mesylate, she had
      further hepatic metastases. The third child was a 4-year-old boy who recently
      underwent a partial gastrectomy and has no signs of metastatic disease at this
      time. CONCLUSIONS: GISTs are unusual tumors that have been rarely described in
      children. When they arise in the stomach, they often present after upper
      gastrointestinal bleeding. Diagnosis can be made by endoscopy and biopsy. GISTs
      require resection and close observation for hepatic metastases. Current studies
      are ongoing for the potential role of Imatinib Mesylate for GISTs in children.

PMID- 15486894
TI  - Surgical therapy of the thyroid papillary carcinoma in children: experience with
      56 patients < or =16 years old.
AB  - BACKGROUND/PURPOSE: This article is an anatomic, clinical, therapeutic, and
      prognostic assessment of 56 children 16 years of age or younger, who underwent a
      surgical operation for thyroid papillary carcinoma from April 1988 to December
      2001 in the Department of General Surgery at the University of Pisa. Of these 56
      patients, 22 are Belarus children (39%) in whom carcinoma developed after the
      nuclear accident in Chernobyl in April 1986, whereas 34 (61%) are children with
      differentiated nonirradiated tumors. The purpose of this work was to compare the
      group of children who had radiation-induced thyroid carcinoma with the group
      affected by non-radiation-induced carcinoma to evaluate if there are significant
      clinical, anatomic, and prognostic differences between them and to identify the
      best surgical strategy to adopt. RESULTS: At the time of clinical presentation,
      the tumor was limited to the thyroid gland in 28 cases (50%), whereas in the
      others, in 24 cases (43%) metastases in the neck lymph nodes were present or had
      infiltrated the extrathyroid tissues as was seen in 4 cases (7%). The surgical
      operation was a total thyroidectomy in 37 cases (66%), whereas in 19 patients
      with radiation-induced carcinoma it was a hemithyroidectomy followed by a
      completion of thyroidectomy in Pisa (34%). The histologic examination showed
      multifocal sites of papillary adenocarcinoma in the gland in 23% of cases, and
      both lobes of the thyroid gland were involved with tumor in 23% of patients. The
      postsurgical follow-up showed a mortality rate of 0% and a recurrence rate of
      33.5% (64% radiation-induced carcinoma v 3% non-radiation-induced carcinoma; P <
      .0001). At the moment, 8 of 22 cases (36%) with radiation-induced carcinoma are
      free of disease versus 33 of 34 (97%) with non-radiation-induced carcinoma (P <
      .0001). CONCLUSIONS: These findings show carcinoma of the thyroid in children has
      a low risk of mortality but a high risk of recurrence. Children with radiation
      induced thyroid carcinoma are more likely to have a recurrence of the disease.
      Total thyroidectomy for the treatment of both radiation-induced and non-radiation
      induced carcinomas appears to represent, on the basis of these results, the best
      therapeutic option.

PMID- 15486895
TI  - CXCR4 expression in neuroblastoma primary tumors is associated with clinical
      presentation of bone and bone marrow metastases.
AB  - BACKGROUND/PURPOSE: The chemokine receptor, CXCR4, has been implicated in the
      mechanism of tumor cell metastasis to bone and bone marrow. Neuroblastoma, a
      cancer of children, is well known for its potential to metastasize to these
      sites. The goal of this study was to investigate whether the degree of expression
      of CXCR4 on cells from neuroblastoma primary tumors was related to the pattern of
      metastatic involvement. METHODS: Archived neuroblastoma primary tumor samples and
      clinical data were collected from 26 patients with newly diagnosed neuroblastoma.
      Expression of CXCR4 (12g5 antibody) was evaluated on formalin-fixed paraffin
      embedded tumor tissues using standard immunohistochemical techniques. Each tumor
      was graded (grade 1 through 4) based on the proportion of cells that were
      positive for the 12g5 antibody. Tumor grades for CXCR4 expression were compared
      with clinical data from each patient. RESULTS: Higher grades of expression (grade
      3 and 4) were found in tumors from patients with high-stage disease (P < .01) and
      in patients with bone and bone marrow metastases (P < or = .01). Clinical outcome
      in patients with tumors highly expressing CXCR4 was significantly worse (P < .01)
      than in those patients with low-grade CXCR4. CONCLUSIONS: CXCR4 expression in
      neuroblastoma primary tumors is significantly correlated with the pattern of
      metastatic spread.

PMID- 15486896
TI  - Role of urokinase plasminogen activator and its receptor in metastasis and
      invasion of neuroblastoma.
AB  - BACKGROUND/PURPOSE: Urokinase plasminogen activator (uPA) is a serine proteinase
      that has been suggested to play an important role in tumor invasion and
      metastasis. It binds to a specific membrane receptor, uPA receptor (uPAR), and
      activates plasminogen to form plasmin, which participates in tissue degradation
      and proteolysis. Binding of uPA to its receptor accelerates the activation of uPA
      from pro-uPA, enhancing the activity of the uPA/uPAR cascade. Because of the high
      metastatic and invasive potential of neuroblastoma (NB) cells, the authors have
      analyzed in the current study, the concomitant of uPA and its receptor in NB.
      METHODS: The expression and distribution of uPA and uPAR were analyzed by
      immunostaining in 52 neuroblastoma tissues; at the same time we use the reverse
      transcriptase polymerase chain reaction (RT-PCR) for neuroendocrine protein gene
      products 9.5 (PGP 9.5) mRNA to detect small numbers of NB cells in the peripheral
      blood and bone marrow (BM) and study the relationship uPA and uPAR to the ability
      of invasion and metastasis of NB cells. To identify risk factors for disease
      progression, the authors performed a retrospective analysis of clinical (age,
      sex, and risk group) and tumor biologic markers (histology, MYCN, DNA ploidy,
      chromosome 1 p, PGP9.5, uPA, uPAR, and combined uPA and uPAR) in all patients.
      Survival curves were estimated using the Kaplan-Meier method. Univariate analysis
      was performed with the log-rank test. Multivariate analysis was performed using
      the Cox proportional hazards regression model. RESULTS: The results of
      immunohistochemistry showed that uPA and uPAR were localized mainly in the
      membrane and cytoplasm of tumor cells. The positive rate of uPA in the high-risk
      group (23 of 25, 92.0%) was remarkably higher than that in intermediate-risk
      group (8 of 17, 47.1%) and low-risk group (3 of 10, 30.0%), in UH (26 of 29,
      89.7%) was higher than in FH (8 of 23, 34.8%), respectively, and statistical
      significance was remarkable both P < .01). Similar results were obtained for
      uPAR. The positive rate of uPAR in the high-risk group (22 of 25, 88.0%) was
      substantially higher compared with that in intermediate-risk group (6 of 17,
      35.3%) and low-risk group (2 of 10, 20.0%; P < .01). The positive rate of uPAR in
      UH (24 of 29, 82.8%) was higher compared with that in FH (6 of 23, 26.1%), and
      statistical significance was remarkable (P < .01). PGP9.5 mRNA in peripheral
      blood and BM was detected in 24 of 52 (45.2%) patients. The positive rate of PGP
      9.5 mRNA in peripheral blood and BM in the cases positive for uPA (22 of 34,
      64.7%) was markedly higher than that in the cases negative for uPA (11.1%, 2 of
      18), and statistical significance was remarkable (P < .01). There was significant
      difference in the positive rate of PGP9.5 mRNA between the group positive for
      uPAR (66.7%, 20 of 30) and the group negative for uPAR (18.2%, 4 of 22), and a
      larger difference was found between the group positive for both uPA and uPAR
      (73.1%, 19 of 26) and the group negative for uPA or uPAR (19.2%, 5 of 26). The
      overall survival (OS) and event-free survival (EFS) rates at 5 years for all
      patients were, respectively, 70% +/- 3% and 63% +/- 3% with a median follow-up of
      65 months (range 13 to 20). Among all the biologic and clinical features
      analyzed, multivariate analysis using Cox proportional hazards regression showed
      that age, MYCN, and combined uPA and uPAR remained significant predictors for
      both OS and EFS (P < .01, respectively). Both EFS rate and OS rate were
      significantly better for patients who positively expressed uPA and uPAR than
      those who negatively expressed uPA or uPAR. CONCLUSIONS: This study showed that
      uPA and uPAR were overexpressed in high-risk and UH tumor of NB, and that
      overexpression of both factors was associated with the ability of invasion,
      metastasis, and prognosis of NB. The presence of high levels of combined uPA and
      uPAR may be a new prognostic marker that would allow us to identify patients with
      poorer prognosis who might benefit from more aggressive surgical and adjuvant
      treatment.

PMID- 15486897
TI  - Factors influencing early failure of central venous catheters in children with
      cancer.
AB  - BACKGROUND: The authors report the results of a prospective, multicenter,
      multidisciplinary study of central venous catheters (CVCs) in pediatric oncology
      patients analyzing factors involved in early failure. METHODS: Information was
      collected from parent-held records on the fate of 824 devices inserted over a 20
      month period, 415 of which were no longer in situ. RESULTS: Within the first 7
      weeks after insertion, there were 66 failures, all occurring in external lines.
      Accidental dislodgement was the principal reason for CVC failure (44 of 66, 67%).
      Detailed analysis of the reason for failure of this large subgroup showed 11
      factors individually associated with early dislodgement, of which, 4 were
      independently associated with failure by multivariate analysis. These 4 variables
      were the use of multilumen catheters, the absence of a skin exit site suture,
      platelet transfusion at the time of insertion, and patient age less than 2 years.
      CONCLUSIONS: This study confirms the multiple influences on successful CVC usage.
      Our analysis supports the principle of only using multilumen lines when
      clinically essential. The findings also support the inception of randomized
      studies of fixation, particularly in infants.

PMID- 15486898
TI  - Lung function in lambs with diaphragmatic hernia after reversible fetal tracheal
      occlusion.
AB  - BACKGROUND/PURPOSE: Short-duration resuscitation (< or =4 hours) of lambs with
      diaphragmatic hernia treated in utero with tracheal occlusion have shown improved
      lung function compared with untreated diaphragmatic hernia. This may be a
      transient phenomenon in the treated diaphragmatic hernia lambs because of
      surfactant deficiency. Our objective was to analyze the effect of fetal tracheal
      occlusion with or without release of the occlusion 1 week before delivery on
      pulmonary function during a longer period of resuscitation (8 hours) in the
      diaphragmatic hernia lamb model. METHODS: Four groups were compared:
      diaphragmatic hernia (n = 5), diaphragmatic hernia and tracheal occlusion until
      delivery (n = 5), diaphragmatic hernia and tracheal occlusion with release of the
      occlusion 1 week before delivery (n = 5), and normal controls (n = 4). RESULTS:
      Despite persistently decreased surfactant levels, diaphragmatic hernia lambs
      treated with tracheal occlusion had normal-sized lungs with marked improvement in
      lung function and gas exchange over 8 hours when compared with untreated lambs
      with diaphragmatic hernia. Release of the tracheal occlusion 1 week before
      delivery added no benefit. CONCLUSIONS: It appears that surfactant-independent
      mechanisms such as pulmonary growth and structural changes are of foremost
      importance in relating to improved compliance, oxygenation, and ventilation of
      diaphragmatic hernia lambs treated with tracheal occlusion.

PMID- 15486899
TI  - Surgical treatment of bronchiectasis in children.
AB  - BACKGROUND PURPOSE: Surgical treatment of childhood bronchiectasis has not been
      discussed extensively because of decline in prevalence and experience with this
      disease. It remains controversial as to which children would benefit from surgery
      and surgical points that may affect the outcome. Therefore, a retrospective
      series was prepared to evaluate the results of surgical treatment of
      bronchiectasis in children. METHODS: The records of 54 children who underwent
      surgery for bronchiectasis between 1991 and 2002 were analyzed retrospectively
      for age; sex; clinical features; radiologic examinations; details of surgery
      including type of resection, operative morbidity, and mortality; and outcome.
      RESULTS: Fifty-four patients underwent 58 pulmonary resections during the study
      period. The mean ages at diagnosis of bronchiectasis and at the time of surgery
      were 7.80 +/- 3.70 years (range, 1 to 15 years) and 9.25 +/- 3.92 years (range,
      1.5 to 17 years), respectively, with a male to female ratio of 5:4. The causes of
      bronchiectasis were lung infection (n = 39), hereditary and inborn diseases (n =
      14), and foreign body aspiration (n = 1). Chest X-rays, bronchography (n = 12) or
      chest computed tomography (n = 43), and ventilation-perfusion scintigraphy (n =
      13) were used, and pulmonary function tests (n = 21) and bronchoscopy (n = 54)
      were performed. The types of resections were lobectomy (63%), pneumonectomy
      (18.5%), lobectomy with segmentectomy (11.1%), segmentectomy (3.7%), and
      bilobectomy (3.7%). Four patients required a second operation. Forty-one patients
      (76%) had complete resection, and 13 patients (24%) had incomplete resection.
      Intraoperative and postoperative complications were encountered in 4 (7.4%) and 4
      patients (7.4%), respectively. The course after surgery was well in 23 (42.5%),
      improved in 23 (42.5%), and unchanged or worse in 5 patients (9.4%). The
      mortality rate was 5.6%. CONCLUSIONS: The decision for bronchiectasis surgery
      should be made in cooperation with the chest diseases unit. Anatomic localization
      of the disease should be mapped clearly by radiologic and scintigraphic
      investigations. The morbidity and mortality rates of bronchiectasis surgery are
      within acceptable ranges. Most of the children benefit from surgery, especially
      when total excision is accomplished. Pneumonectomy is well tolerated in children
      without increase in morbidity and mortality. Therefore, pneumonectomy may be
      preferred instead of leaving residual disease when bronchiectasis is unilateral.

PMID- 15486900
TI  - Can esophageal pH monitoring predict delayed gastric emptying?
AB  - BACKGROUND/PURPOSE: Delayed gastric emptying (DGE) is frequent in patients with
      gastroesophageal reflux disease (GERD) and may require additional investigation.
      The current study assesses whether relative esophageal exposure, postprandial
      (PP) versus fasting, diagnosed by pH monitoring could predict DGE. METHODS:
      Thirty patients with GERD underwent extended esophageal pH monitoring and were
      assigned as DGE or non-DGE according to scintigraphy. The PP to fasting ratio for
      reflux index, relative frequency of long episodes in PP, and distribution of the
      longest episode were used to assess the relative esophageal exposure. The
      effectiveness of these parameters to predict DGE was estimated; the cutoffs for
      continuous variables were chosen with receiver operating characteristics (ROC)
      curves and the probabilities were calculated using a logistic regression model.
      RESULTS: The area under the ROC curve of PP to fasting ratio for reflux index was
      greater than that of relative frequency of long episodes in PP. There was a good
      equilibrium between sensitivity and specificity at a PP to fasting ratio of 1. A
      PP to fasting ratio greater than 1, ie, a reflux index in PP greater than in
      fasting, presented a sensitivity of 93% and a negative predictive value of 91%.
      The occurrence of the longest episode in PP had a specificity of 94% and a
      positive predictive value of 89%. A reflux index greater in PP plus a longest
      episode in PP presented a 94% probability of DGE; a reflux index greater in
      fasting plus a longest episode in fasting had a 95% probability of non-DGE. These
      combinations represented 60% of the series. CONCLUSIONS: PP to fasting ratio for
      reflux index and distribution of the longest episode seem accurate to identify
      DGE; thus, additional investigation to assess gastric emptying may be avoided in
      the majority of patients.

PMID- 15486901
TI  - Gastroschisis in the rat model is associated with a delayed maturation of
      intestinal pacemaker cells and smooth muscle cells.
AB  - BACKGROUND: A pacemaker system is required for peristalsis generation. The
      interstitial cells of Cajal (ICC) are considered the intestinal pacemaker, and
      are identified by expression of the c-kit gene--encoded protein. Gastroschisis is
      characterized by a severe gastrointestinal dysmotility in newborns. In spite of
      this clinical picture, few studies have focused on smooth muscle cells (SMC)
      morphology and none on ICC. Therefore, their morphology has been studied in
      fetuses at term in the rat model of gastroschisis. METHODS: At 18.5 day's
      gestation (E18.5), 10 rat fetuses were killed, 10 underwent surgical creation of
      gastroschisis, and 10 underwent manipulation only. The small intestine of the
      latter 2 groups was harvested at E21.5. Specimens were processed for H&E, c-kit
      and actin (alpha smooth muscle antibody [alpha-SMA]) immunohistochemistry, and
      transmission electron microscopy (TEM). RESULTS: In the controls, SMC were c-kit+
      and alpha-SMA+, with labeling intensity increasing by age. At E21.5, some cells
      around the Auerbach's plexus were more intensely c-kit+, and differentiating ICC
      were seen under TEM at this level. Gastroschisis fetuses had no c-kit+ cells
      referable to ICC. In the more damaged loops, SMC were very faintly c-kit+ and
      alpha-SMA+. Under TEM, there were few differentiated SMC and no presumptive ICC.
      In the less-damaged loops, SMC were faintly c-kit+ and alpha-SMA+ and had
      ultrastructural features intermediate between those of E18.5 and E21.5 controls;
      ICC were very immature. CONCLUSIONS: ICC and SMC differentiation is delayed in
      gastroschisis with the most damaged loops showing the most incomplete picture.
      These findings might help in understanding the delayed onset of peristalsis and
      the variable time-course of the recover seen in babies affected by gastroschisis.

PMID- 15486902
TI  - Persistent elevation of serum interleukin-6 in intraabdominal sepsis identifies
      those with prolonged length of stay.
AB  - BACKGROUND/PURPOSE: Elevated serum interleukin-6 (IL-6) levels in patients with
      intraabdominal sepsis have been associated with increased morbidity and
      mortality. The authors hypothesized that after surgical intervention a persistent
      elevation of IL-6 would more accurately reflect the inflammatory state and thus
      predict the subsequent time to recovery better than the preoperative value alone.
      METHODS: Nineteen consecutive children with peritonitis and manifestations of the
      systemic inflammatory response syndrome were enrolled prospectively. IL-6 levels
      were determined from pre- and postoperative serum samples (within 12 to 24 hours)
      by enzyme-linked immunosorbant assay (ELISA). Patient postoperative length of
      stay (LOS) was recorded. RESULTS: Before surgery, patient serum IL-6 levels
      ranged from 48 to 132,546 pg/mL. LOS ranged from 4 to 60 days, with subjects
      falling into 2 groups of < or =11 (n = 14) and > or =25 (n = 5) days. Using an IL
      6 level greater than 500 pg/mL to predict a prolonged LOS (>11 days), a
      persistent elevation of IL-6 postoperatively appears to increase the likelihood
      of a prolonged LOS. CONCLUSIONS: Persistent IL-6 levels greater than 500 pg/mL
      may be useful in identifying pediatric intraabdominal sepsis patients with
      prolonged LOS and presumably greater morbidity. Rapid identification of these
      patients may allow for novel therapeutic interventions.

PMID- 15486903
TI  - Impaired absorption of marked oligopeptide Glycine-I Tyrosine-Glycine after
      successful autologous-allotopic ileal mucosa transplantation in beagles.
AB  - PURPOSE: After establishing a method for ileal mucosa transplantation in an
      animal model, the authors investigated the absorptive capacity for oligopeptides
      of the transplanted mucosa. METHODS: In 14 beagle dogs the authors transplanted
      ileal mucosa in a vascularized demucosed segment of the transverse colon. The
      colonic wall-ileal mucosa complex then was integrated in the ileal continuity.
      Six animals were lost owing to operative complications. Absorptive capacity for
      oligopeptides was measured in the remaining 8 animals with the iodine 131 (131I)
      marked tripeptide glycine-tyrosine-glycine before and 4 weeks after
      transplantation. The results were compared and analyzed with the Student's t test
      for matched pairs. Blood concentrations of the marked tripeptide with P value
      less than .05 were considered as a significant reduction in the absorptive
      capacity of the transplanted ileal mucosa. After fixation with glutaraldehyd
      graft, uptake of the colonic wall-ileal mucosa complex was evaluated
      histologically in 8 animals. RESULTS: In all 8 animals, a 100% graft uptake was
      verified in all sections. Fifteen minutes after application of 15 MBc Glycine
      131I-Tyrosine-Glycine there was no significant difference in the absorption
      between normal and transplanted ileal mucosa. After 30 minutes, the absorption of
      the transplanted ileal mucosa showed a tendency (P < .1) for an impaired uptake
      of the marked tripeptide. However, 60 minutes after application the difference in
      the absorptive capacity of the transplanted ileal mucosa was significant (P <
      .05). CONCLUSIONS: Autologous allotopic ileal mucosa transplantation is feasible;
      however, an impaired absorption of oligopeptides of the transplanted mucosa 4
      weeks after transplantation could be observed.

PMID- 15486904
TI  - The length and collapsibility of the ureter play roles in the augmented
      reflection of intraabdominal pressure into the renal pelvis.
AB  - BACKGROUND/PURPOSE: Flow of a fluid through a collapsible tube is under the
      influence of various factors including the external compressing pressure. The
      intraabdominal pressure (IAP) should influence the flow through the ureter.
      Therefore, an experimental study was planned to investigate the effects of
      ureteral length and external compressing pressure onto the intrapelvic pressure
      (IPP) in rabbits. METHODS: Nineteen adult rabbits were used for the experiment.
      Under general anesthesia, an intraperitoneal and an intrapelvic catheter were
      placed to measure IAP and IPP. A urethral catheter was placed for bladder
      decompression. After this standard preparation, a ureteric stent was placed in
      the ureter in group 1 (n = 7). Distal or proximal ureter transection was
      performed in group 2 (n = 6) and group 3 (n = 6), respectively. Basal pressure
      measurements have been recorded. Then the pressures were recorded every 5
      minutes, and IAP was increased gradually for 4 cm of water pressure in each
      subsequent 30-minute period. All analyses were performed for a standard IAP
      interval (5 to 25 cm H2O). RESULTS: IAP did not differ between groups (P = .08).
      IPP values were significantly higher than the corresponding IAP values in each
      group (P = .0001). IPP showed significant difference between IAP values of groups
      (P = .0001). IPP was significantly increased in group 2 when compared with group
      1 and group 3 (P = .0001; P = .0001), but no difference was encountered between
      groups 1 and 3 (P = .1). There has been a strong relationship between IPP and IAP
      values in all groups. The Rsq values were 0.912, 0.783, and 0.943 for group 1,
      group 2, and group 3, respectively (P < .0001). Mathematic relations between IPP
      and IAP also were analyzed. The relations were IPP = 3.9 + 1.10 x IAP, IPP = 10.3
      + 1.10 x IAP, and IPP = 3.3 + 1.12 x IAP for groups 1, 2, and 3, respectively.
      CONCLUSIONS: Renal pelvis pressure responds with augmented increases to
      increments in IAP in urinary tracts with different ureteric lengths. Increase in
      IPP is more pronounced in longer ureters possibly owing to increased resistance
      to flow. Prevention of ureteric wall collapse reverses the augmented increase in
      IPP responses. Therefore, both the length and collapsibility of the ureter play a
      detrimental role in the generation of augmented IPP responses to increments in
      IAP. The magnitude of IPP as a response to increments in IAP can be estimated by
      using mathematical relations between IPP and IAP. Increases in IAP may simulate
      proximal ureteric obstruction and may take part in the pathogenesis of
      hydronephrosis.

PMID- 15486905
TI  - Circumcision in hemophilia: a cost-effective method using a novel device.
AB  - BACKGROUND/PURPOSE: The authors conducted a prospective clinical study to see
      whether the need for and the cost of factor substitution after circumcision can
      be reduced using a novel device for bloodless circumcision in boys with
      hemophilia. METHODS: Forty-five boys with hemophilia (age range, 1.5 to 25 years;
      median age, 11; 40 with hemophilia A, 5 with hemophilia B; weight range, 9 to 75
      kg; median weight, 30 kg) were circumcised in our department between 1996 and
      2001. Severity of the disease was mild in 9 cases, moderate in 11, and severe in
      25. After starting systemic prophylaxis including factor substitution and DDAVP
      (desmopressin acetate) in reduced doses, all patients underwent circumcision
      under local anesthesia using a modified straight clamp and a battery-operated
      diathermic knife specially designed for bloodless circumcision. Duration of
      factor replacement ranged between 7 and 18 days, and the hospitalization period
      was 2 to 5 days according to severity of the disease. The last 19 patients were
      given tranexamic acid orally for 7 days after surgery. RESULTS: Transient minimal
      bleeding was observed in 5 patients and easily responded to factor
      administration. Moderate edema and hyperemia along the excision line owing to the
      diathermic effect of the device lasted for 3 to 4 days. Normal cosmetic
      appearance was regained within 7 to 21 days. Excellent patient and family
      satisfaction was reported. The average cost of the operation was calculated as 81
      dollars, 144 dollars, and 243 dollars per kilogram in mild, moderate, and severe
      cases, respectively. CONCLUSIONS: Bloodless circumcision with "diathermic knife"
      is a practical and reliable alternative for boys with hemophilia. Enhancement of
      local hemostasis using such an alternative device may reduce the need for factor
      substitution and, accordingly, the cost of circumcision in hemophiliacs, down to
      50%.

PMID- 15486906
TI  - Tumor recurrence at thoracostomy tube insertion sites: a report of two pediatric
      cases.
AB  - Recurrence of thoracic malignant tumors at port sites used for thoracoscopic
      procedures in adults have been described. However, there are no reports of tumor
      recurrence at thoracostomy tube or thoracoscopic trocar insertion sites after
      operation for thoracic malignancies in children. The authors report 2 cases of
      tumor recurrence at thoracostomy tube insertion sites after intraoperative gross
      spillage of pleuropulmonary blastoma and malignant epithelial thymoma and discuss
      approaches that may potentially prevent this devastating complication.

PMID- 15486907
TI  - Thoracoscopic repair of H-type tracheoesophageal fistula in the newborn: a
      technical case report.
AB  - H-type tracheoesophageal fistula (H-TEF) without esophageal atresia makes up 4%
      to 5% of esophageal congenital abnormalities. The authors present the
      thoracoscopic treatment of a 2.47-kg newborn boy with a fistula between the
      second and third thoracic vertebrae diagnosed by esophagography. Four trocars
      were used for fistula closure, and tracheal and esophageal suturing were
      accomplished without intraoperative incident. Five days after surgery, results of
      a barium swallow excluded anastomotic leaks. The chest tube was removed, and oral
      feeding was initiated.

PMID- 15486908
TI  - Endoscopic management of the intranasal glioma.
AB  - The authors report the endoscopic management of a boy with nasal glioma who was
      only 35 days old. The nasal glioma is a rare congenital nasal abnormality, which
      manifests as a mass of extracranial cerebral tissue unconnected with the brain.
      For surgical excision, some surgeons suggest initial craniotomy for excluding
      intracranial extension. The authors successfully removed the intranasal glioma by
      endoscopic surgery without craniotomy on a 35-day-old boy. Intranasal endoscopic
      surgery is a less-invasive and safe procedure and does not result in
      postoperative facial scarring and deformity. Therefore, the use of endoscopic
      surgery in place of lateral rhinotomy procedure is recommended.

PMID- 15486909
TI  - Mucinous cystadenoma of the pancreas in a one-year-old child.
AB  - Mucinous cystadenomas of the pancreas are uncommon lesions in adults and even
      more rare in children. This report presents a case of a pancreatic mucinous
      cystadenoma in a 1-year-old boy and offers a review of the literature and
      discussion of the surgical implications.

PMID- 15486910
TI  - Staphylococcal rib osteomyelitis in a pediatric patient.
AB  - Osteomyelitis in children commonly occurs in the long bones such as the femur,
      tibia, and humerus. It is rarely found in the ribs, occurring in less than 1% of
      children with osteomyelitis. Thirteen cases of rib osteomyelitis were reported in
      the literature, of which, 11 were caused by Staphylococcus aureus. Pediatric
      osteomyelitis often masquerades as skeletal neoplasia, as illustrated in the
      following case presentation. Here, the authors describe a case of pediatric
      staphylococcal rib osteomyelitis, review the published literature on similar
      cases, and describe its medical and surgical treatment.

PMID- 15486911
TI  - Primary germ cell tumor of the diaphragm.
AB  - The authors present a case of a 2-year-old boy with an abdominal mass, which was
      later found to be a yolk sac tumor arising from the diaphragm. To the authors'
      knowledge there has been only 1 previous report of a germ cell tumor arising from
      the diaphragm. This case illustrates the imaging findings in this rare tumor and
      how it could be confused with a primary liver neoplasm.

PMID- 15486912
TI  - Esophageal atresia and achalasialike esophageal dysmotility.
AB  - A 14-year-old boy presented with regurgitation, malnutrition, and chronic lung
      insufficiency with a history of successful repair of esophageal atresia and
      tracheoesophageal fistula in the newborn period. Barium swallow and manometry
      results showed achalasia. Hellar operation with antireflux procedure resulted in
      complete symptomatic relief. Histology and immunohistochemistry including PGP9.5,
      MAP5, cKit, and nNOS of myotomy specimen showed intact innervation. Although
      esophageal dysmotility after esophageal atresia repair usually is caused by
      gastroesophageal reflux and incoordination of peristalsis, the possibility of
      achalasia should also be considered, because a casual relationship between
      esophageal atresia and achalasia may exist.

PMID- 15486913
TI  - An unusual type of severe barotrauma owing to automobile tire biting in a child.
AB  - The authors report a rare case of a barotraumatic pneumothorax and
      pneumomediastinum associated with esophageal perforation and orbital emphysema. A
      4-year-old boy presented with sudden respiratory distress after blowout of a
      defective tire that he bit. Computed tomography scan showed right pneumothorax
      and bilateral orbital emphysema. A linear rupture has been detected in the
      cervical esophagus in esophagoscopy. Stamm gastrostomy and tube thoracostomy were
      performed, and broad-spectrum antibiotics have been introduced. Oral feeding
      started 23 days after blowout of tire, and the patient was discharged 50 days
      after injury.

PMID- 15486914
TI  - Conservative treatment of a mesenteric lymphangiomyomatosis in an 11-year-old
      girl with a long follow-up period.
AB  - The authors report the case of a 11-year-old girl admitted for a mesenteric tumor
      discovered during an appendicectomy. The abdominal Doppler echography and
      computed tomography (CT) scan showed a 8 x 6 x 7-cm multinodular mass involved in
      the mesenterium. Biological markers and iodine 131 meta-iodobenzylguanidine
      (MIBG) scintigraphy results were normal. Percutaneous biopsies were performed.
      Pathology results showed perilymphatic proliferation of smooth muscle cells
      leading to cystic lesions. No sign of malignancy was seen. Laparotomy showed a
      multinodular fixed mass involved from the root of the mesenterium. The superior
      mesenteric vessels were encircled by the tumor, which could not be resected
      completely. Partial resection was performed. The pathology and the
      immunohistochemical tests confirmed the diagnosis of lymphangiomyomatosis. At 21
      years of age, she remains asymptomatic. An echography and CT scan showed the mass
      remaining unchanged in size and echopattern. Lymphangiomyomatosis (LMA) is
      thought to affect exclusively women in their reproductive life, and the steroid
      hormones are supposed to play an essential role in the pathology and in the
      behavior of this condition. Infantile LMA is exceptional. The patient reported is
      remarkable for her young age, the location of the tumor, her long history, and
      her benign course. Because the tumor is supposed to be hormone dependent, the
      surge of oestrogen in this 21-year-old woman may initiate the extensive form of
      lymphangiomyomatosis with pulmonary involvement, the prognosis of which is
      extremely poor.

PMID- 15486915
TI  - Severe ciprofloxacin-associated pseudomembranous colitis in an eight-year-old
      child.
AB  - Clostridium difficile is the principal cause of antibiotic-associated diarrhea
      and pseudomembranous enterocolitis in children. A case of severe pseudomembranous
      colitis developing in an 8-year-old child who had received oral ciprofloxacin
      therapy as part of an investigational protocol is presented. The safety and
      efficacy of fluoroquinolones in children has not yet been established. Use of
      these antibiotics in children outside investigational protocols ("off-label" use)
      as oral antipseudomonas agents is discouraged.

PMID- 15486916
TI  - Duodenal perforation associated with breath stacking and annular pancreas.
AB  - Gastrointestinal perforations have been reported occasionally in neonates. The
      authors describe a 9-month-old girl with mosaic trisomy 8 on home breath-stacking
      therapy who presented with an acute abdomen. A large perforation in the first
      portion of the duodenum was found as well as an incidental annular pancreas.
      Despite occupying approximately half of the circumference of the lumen, the
      perforation was able to be closed primarily without complications. Several
      etiologies have been suggested for intestinal perforations. This report
      hypothesizes the possible involvement of breath stacking in conjunction with
      partial obstruction by an annular pancreas.

PMID- 15486917
TI  - Ileoileal invagination without obstruction in a four-year-old boy.
AB  - Intussusception is one of the most common causes of acute abdomen in the first
      year of life. Its clinical presentation is vomiting, bloody stools, severe
      colicky abdominal pain, and mass. The authors reported a case of intussusception
      with an inappropriate clinical picture, but both characteristic ultrasonography
      and computed tomography findings led to the diagnosis of ileo-ileal
      intussusception.

PMID- 15486918
TI  - Stellate cells: a moving target in hepatic fibrogenesis.

PMID- 15486919
TI  - Unique precipitation and exocytosis of a calcium salt of myo-inositol
      hexakisphosphate in larval Echinococcus granulosus.
AB  - The ubiquitous intracellular molecule myo-inositol hexakisphosphate (IP6) is
      present extracellularly in the hydatid cyst wall (HCW) of the parasitic cestode
      Echinococcus granulosus. This study shows that extracellular IP6 is present as
      its solid calcium salt, in the form of deposits that are observed, at the
      ultrastructural level, as naturally electron dense granules some tens of
      nanometers in diameter. The presence of a calcium salt of IP6 in these structures
      was determined by two different electron microscopy techniques: (i) the analysis
      of the spatial distribution of phosphorus and calcium in the outer, acellular
      layer of the HCW (the laminated layer, LL) through electron energy loss
      spectroscopy, and (ii) the observation, by transmission electron microscopy, of
      HCW that were selectively depleted of IP6 by treatment with EGTA or phytase, an
      enzyme that catalyses the dephosphorylation of IP6. The deposits of the IP6
      Ca(II) salt are also observed inside membrane vesicles in cells of the germinal
      layer (the inner, cellular layer of the HCW), indicating that IP6 precipitates
      with calcium within a cellular vesicular compartment and is then secreted to the
      LL. Thus, much as in plants (that produce vesicular IP6 deposits), the existence
      of transporters for IP6 or its precursors in internal membranes is needed to
      explain the compound's cellular localisation in E. granulosus.

PMID- 15486920
TI  - An apoptosis biomarker goes to the HCV clinic.

PMID- 15486921
TI  - Frequent inactivation of the tumor suppressor Kruppel-like factor 6 (KLF6) in
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide,
      reflecting incomplete characterization of underlying mechanisms and lack of early
      detection. Kruppel-like factor 6 (KLF6) is a ubiquitously expressed zinc finger
      transcription factor that is deregulated in multiple cancers through loss of
      heterozygosity (LOH) and/or inactivating somatic mutation. We analyzed the
      potential role of the KLF6 tumor suppressor gene in 41 patients who had HCC
      associated with hepatitis C virus (16 patients), hepatitis B virus (12 patients,
      one of whom was coinfected with hepatitis C virus), and other etiologies (14
      patients) by determining the presence of LOH and mutations. Overall, LOH and/or
      mutations were present in 20 (49%) of 41 tumors. LOH of the KLF6 gene locus was
      present in 39% of primary HCCs, and the mutational frequency was 15%. LOH and/or
      mutations were distributed across all etiologies of HCC evaluated, including
      patients who did not have cirrhosis. Functionally, wild-type KLF6 decreased
      cellular proliferation of HepG2 cells, while patient-derived mutants did not. In
      conclusion, we propose that KLF6 is deregulated by loss and/or mutation in HCC,
      and its inactivation may contribute to pathogenesis in a significant number of
      these tumors.

PMID- 15486922
TI  - Mitochondrial permeability transition in acetaminophen-induced necrosis and
      apoptosis of cultured mouse hepatocytes.
AB  - Acetaminophen overdose causes massive hepatic failure via mechanisms involving
      glutathione depletion, oxidative stress, and mitochondrial dysfunction. The
      ultimate target of acetaminophen causing cell death remains uncertain, and the
      role of apoptosis in acetaminophen-induced cell killing is still controversial.
      Our aim was to evaluate the mitochondrial permeability transition (MPT) as a key
      factor in acetaminophen-induced necrotic and apoptotic killing of primary
      cultured mouse hepatocytes. After administration of 10 mmol/L acetaminophen,
      necrotic killing increased to more than 49% and 74%, respectively, after 6 and 16
      hours. MPT inhibitors, cyclosporin A (CsA), and NIM811 temporarily decreased
      necrotic killing after 6 hours to 26%, but cytoprotection was lost after 16
      hours. Confocal microscopy revealed mitochondrial depolarization and inner
      membrane permeabilization approximately 4.5 hours after acetaminophen
      administration. CsA delayed these changes, indicative of the MPT, to
      approximately 11 hours after acetaminophen administration. Apoptosis indicated by
      nuclear changes, terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling, and caspase-3 activation also increased after acetaminophen
      administration. Fructose (20 mmol/L, an adenosine triphosphate-generating
      glycolytic substrate) plus glycine (5 mmol/L, a membrane stabilizing amino acid)
      prevented nearly all necrotic cell killing but paradoxically increased apoptosis
      from 37% to 59% after 16 hours. In the presence of fructose plus glycine, CsA
      decreased apoptosis and delayed but did not prevent the MPT. In conclusion, after
      acetaminophen a CsA-sensitive MPT occurred after 3 to 6 hours followed by a CsA
      insensitive MPT 9 to 16 hours after acetaminophen. The MPT then induces ATP
      depletion-dependent necrosis or caspase-dependent apoptosis as determined, in
      part, by ATP availability from glycolysis.

PMID- 15486923
TI  - PTFE-covered stents improve TIPS patency in Budd-Chiari syndrome.
AB  - Transjugular intrahepatic portosystemic shunt (TIPS) have been shown to be an
      efficient portal-systemic derivative treatment for Budd-Chiari syndrome (BCS)
      patients uncontrolled by medical therapy. However, the main drawback of TIPS for
      this condition is a very high rate of shunt dysfunction. Recently,
      polytetrafluoroethylene (PTFE)-covered stents have been shown to reduce the
      incidence of TIPS dysfunction in patients with cirrhosis. The aim of the study
      was to assess the incidence of TIPS dysfunction in 2 cohorts of BCS patients
      treated with bare or PTFE-covered stents. The study included 25 TIPS procedures
      (16 bare stents and 9 covered stents) with a median follow-up period of 20.4
      months (range, 3.9-124.8). Fourteen of 16 patients (87%) receiving bare stents
      had TIPS dysfunction compared to 3 of the 9 patients (33%) receiving PTFE-covered
      stents (P = .005). The actuarial rates of primary patency in the bare-stent group
      were 19% at 1 year compared with 67% in the PTFE-covered stent group (P = .02;
      log-rank test). The number of additional interventional procedures to maintain
      TIPS patency was significantly greater in the bare-stent than in the PTFE-covered
      stent group (1.9 +/- 1.2 vs. 0.6 +/- 0.9; P = .007). The number of patients with
      clinical relapses was greater in the bare-stent group compared to the PTFE
      covered stent group (13 vs. 5 episodes in 9 and 3 patients, respectively). In
      conclusion, PTFE-covered stents have a considerable advantage over bare stents
      for the TIPS treatment of BCS patients, with a lower dysfunction rate, a lower
      number of reinterventions, and fewer prosthesis requirements. PTFE-covered stents
      are preferable in patients with Budd-Chiari Syndrome.

PMID- 15486924
TI  - Repeated visual hallucinations in Parkinson's disease as disturbed
      external/internal perceptions: focused review and a new integrative model.
AB  - Visual hallucinations (VH) in Parkinson's disease (PD) are a chronic complication
      in 30 to 60% of treated patients and have a multifaceted phenomenology.
      Flickering, faultive impressions, and illusionary misperceptions precede the core
      syndrome of stereotyped, colorful images. The patient variably recognizes these
      images as hallucinations, being rarely irritated or frightened and more often
      amused as a bystander. Although studies on VH in PD focus on several research
      domains, no comprehensive, unified theory has been developed to study their
      pathophysiology. We have adapted Hobson's work on the states of consciousness and
      propose a model integrating seemingly disparate data on VH. We suggest that VH
      should be considered as a dysregulation of the gating and filtering of external
      perception and internal image production. Contributive elements and anatomical
      links for the model include poor primary vision, reduced activation of primary
      visual cortex, aberrant activation of associative visual and frontal cortex, lack
      of suppression or spontaneous emergence of internally generated imagery through
      the ponto-geniculo-occipital system, intrusion of rapid eye movement dreaming
      imagery into wakefulness, errative changes of the brainstem filtering capacities
      through fluctuating vigilance, and medication-related overactivation of
      mesolimbic systems. Different etiologies likely produce different phenomenologies
      and the prognosis may not be uniform. This new conceptual framework permits an
      anatomical view of VH and suggests new, testable hypotheses regarding their
      pathophysiology and therapy.

PMID- 15486925
TI  - An immunomodulatory role for CD4(+)CD25(+) regulatory T lymphocytes in hepatitis
      C virus infection.
AB  - The CD4(+)CD25(+) regulatory T lymphocytes have been implicated in suppressing T
      cell immune responses. Our aim was to characterize the frequency, phenotype,
      function, and specificity of CD4(+)CD25(+) T cells in hepatitis C virus (HCV)
      infection. Peripheral CD4(+)CD25(+) cells from recovered (n = 15), chronic
      infected (n = 30), and normal control (n = 15) subjects were analyzed ex vivo for
      quantitation, phenotype, and effect on HCV-specific interferon gamma production
      and proliferation. CD4(+)CD25(+) specificity was determined by intracellular
      cytokine staining for interleukin 10 (IL-10). A higher proportion of
      CD4(+)CD25(+) were found in chronic infection (mean, 3.02%) when compared with
      recovered (1.64%, P = .001) and normal controls (2.27%, P = .02). CD4(+)CD25(+)
      cells display CD45RO(high), CD45RA(low), CD28(high), CD62L(high), and CD95(high)
      phenotype. HCV-specific interferon gamma activity was enhanced in peripheral
      blood mononuclear cells depleted of CD4(+)CD25(+) and suppressed in peripheral
      blood mononuclear cells enriched with CD4(+)CD25(+). Depletion of CD4(+)CD25(+)
      cells also enhanced HCV-specific CD4(+) and CD8(+) T cell proliferation. Cytokine
      analysis suggested CD4(+)CD25(+) cells secrete transforming growth factor beta
      (TGF-beta(1)) and IL-10. The inhibitory role for TGF-beta(1) was confirmed by
      anti-TGF-beta(1). Transwell studies showed CD4(+)CD25(+) mediated suppression to
      be dose dependent and requiring cell contact. CD4(+)CD25(+) cells showed HCV
      specificity through IL-10 production, with a frequency ranging from 1.9% to 5.3%.
      A positive correlation was detected between CD4(+)CD25(+) T cell frequency and
      HCV RNA titer, whereas an inverse relation was found with liver inflammatory
      activity. In conclusion, CD4(+)CD25(+) T lymphocytes constitute a highly
      differentiated population and appear to play a role in viral persistence by
      suppressing HCV-specific T cell responses in a cell-cell contact manner.

PMID- 15486926
TI  - Occult hepatitis B virus infection in a North American adult hemodialysis patient
      population.
AB  - Hepatitis B virus (HBV) infections continue to occur in adult hemodialysis units.
      A possible contributing factor is the presence of occult HBV (serum hepatitis B
      surface antigen [HBsAg] negative but HBV DNA positive). Two hundred forty-one
      adult hemodialysis patients were screened for occult HBV. HBV DNA testing was
      performed by real-time polymerase chain reaction (PCR) with 2 independent primer
      sets (core promoter and surface). Two (0.8%) of the 241 patients were HBsAg
      positive. Of the remaining 239 HBsAg-negative patients, 9 (3.8%) were HBV DNA
      positive. Viral loads in these individuals were low (10(2)-10(4) viral
      copies/mL). Seven of the 9 (78%) were nt 587 mutation (sG145R mutant) positive.
      Demographic, biochemical, and HBV serological testing did not help to identify
      those with occult HBV. In conclusion, the prevalence of occult HBV in adult
      hemodialysis patients in this North American urban center is approximately 4 to 5
      times higher than standard HBsAg testing would suggest. The majority of these
      infections are associated with low viral loads and a high prevalence of the
      sG145R mutant. Finally, the demographic, biochemical, and/or serological features
      of HBV DNA-positive subjects do not distinguish these individuals from the
      remainder of the dialysis patient population.

PMID- 15486927
TI  - Detection of apoptotic caspase activation in sera from patients with chronic HCV
      infection is associated with fibrotic liver injury.
AB  - Chronic hepatitis C virus (HCV) infection is characterized by inflammatory liver
      damage and is associated with a high risk of development of cirrhosis and
      hepatocellular carcinoma. Although histological examination of liver biopsies is
      currently the gold standard for the detection of early liver damage, there is a
      strong need for better noninvasive methods. We recently demonstrated that the
      proapoptotic activation of caspases is considerably enhanced in histological
      sections from HCV-infected liver tissue, suggesting an important role of
      apoptosis in liver damage. Here, we investigated whether caspase activation is
      detectable also in sera from patients with chronic HCV infection. Using a novel
      enzyme-linked immunosorbent assay that selectively recognizes a proteolytic
      neoepitope of the caspase substrate cytokeratin-18, we demonstrate that caspase
      activity is markedly increased in the sera of HCV patients. Interestingly, while
      27% of patients with chronic HCV infection showed normal aminotransferase levels
      despite inflammatory and fibrotic liver damage, more than 50% of those patients
      exhibited already elevated serum caspase activity. Moreover, 30% of patients with
      normal aminotransferase but elevated caspase activity revealed higher stages of
      fibrosis. In conclusion, compared with conventional surrogate markers such as
      aminotransferases, detection of caspase activity in serum might be a more
      sensitive method of detecting early liver injury. Thus, measurement of caspase
      activity might provide a novel diagnostic tool, especially for patients with
      normal aminotransferases but otherwise undiagnosed histologically active
      hepatitis and progressive fibrosis.

PMID- 15486928
TI  - ACAT2 deficiency limits cholesterol absorption in the cholesterol-fed mouse:
      impact on hepatic cholesterol homeostasis.
AB  - Acyl CoA:cholesterol acyltransferase (ACAT) 2 is the major cholesterol
      esterifying enzyme in mouse enterocytes and hepatocytes. Male ACAT2(+/+) and
      ACAT2(-/ -) mice were fed chow containing added cholesterol (0%-0.500% w/w) for
      24 days. Over this range, fractional cholesterol absorption in the ACAT2(+/+)
      mice fell from 41.4% +/- 6.6% to 21.0% +/- 5.2%, and in their ACAT2(-/-)
      counterparts it fell from 35.1% +/- 4.5% to 7.9% +/- 0.8%. The mass of dietary
      cholesterol absorbed (mg/d per 100 g body weight) increased from 1.2 +/- 0.2 to
      14.7 +/- 4.4 in the ACAT2(+/+) mice and from 1.0 +/- 0.2 to 5.5 +/- 0.6 in those
      without ACAT2. In the ACAT2(+/+) mice, hepatic cholesterol concentrations
      increased as a function of intake despite compensatory changes in cholesterol and
      bile acid synthesis and in the expression of adenosine triphosphate-binding
      cassette transporter G5 (ABCG5) and ABC transporter G8 (ABCG8). In contrast, in
      ACAT2(-/-) mice in which the amount of cholesterol absorbed at the highest intake
      was only 37% of that in the ACAT2(+/+) mice, suppression of synthesis was a
      sufficient adaptive response; there was no change in bile acid synthesis,
      ABCG5/G8 expression, or hepatic cholesterol concentration. The expression of
      adenosine triphosphate-binding cassette transporter A1 (ABCA1) in the jejunum was
      markedly elevated in the ACAT2(-/-) mice, irrespective of dietary cholesterol
      level. In conclusion, although ACAT2 deficiency limits cholesterol absorption,
      the extent to which it impacts hepatic cholesterol homeostasis depends on
      cholesterol intake. Loss of ACAT2 activity may result in unesterified cholesterol
      being absorbed via an ABCA1-mediated basolateral efflux pathway.

PMID- 15486929
TI  - The opportunity of stem cell bioengineering.

PMID- 15486930
TI  - Cell population dynamics model for deconvolution of murine embryonic stem cell
      self-renewal and differentiation responses to cytokines and extracellular matrix.
AB  - Stem cell self-renewal versus differentiation fate decisions are difficult to
      characterize and analyze due to multiple competing rate processes occurring
      simultaneously among heterogeneous cell subpopulations. To address this
      challenge, we describe a mathematical model for cell population dynamics that
      allows flow cytometry measurement of population distributions of molecular
      markers to be deconvoluted in terms of subpopulation-specific rate parameters
      distinguishing commitment to differentiation, proliferation of differentiated
      cells, and proliferation of undifferentiated cells (i.e., self-renewal). We
      validate this model-based parameter determination by means of dedicated,
      independent cell-tracking studies. Our approach facilitates interpretation of
      relationships underlying effects of external cues on cell responses in
      differentiating cultures via intracellular signals.

PMID- 15486931
TI  - Pivotal role of nuclear factor kappaB signaling in anti-CD40-induced liver injury
      in mice.
AB  - Nuclear factor kappaB (NF-kappaB) has a central role in coordinating the
      expression of a wide variety of genes that control immune responses and is also
      recognized as an antiapoptotic transcription factor. Here, we focused on the role
      of the NF-kappaB signaling pathway in the interaction between inflammatory cells
      and hepatocytes in liver inflammation. We found that pretreatment of mice with
      adenoviruses expressing a mutant form of the inhibitor kappaB superrepressor
      (Ad5IkappaB), a NF-kappaB inhibitor, reduced the migration of inflammatory cells
      and cytokine and chemokine expression in the liver 12 hours after a single
      intravenous injection of an anti-CD40 antibody (alphaCD40) compared with mice
      infected with control adenoviruses (Ad5LacZ). We also confirmed reductions in
      cytokine production by macrophages, T cells, and natural killer (NK) cells in the
      liver of Ad5IkappaB-treated mice by FACS analysis. However, alphaCD40 treatment
      in Ad5IkappaB-infected mice induced elevation of serum alanine aminotransferase
      at 24 hours, and the liver injury was associated with massive hepatocyte
      apoptosis. Furthermore, interferon gamma (IFN-gamma) production by NK cells and T
      cells was increased and stimulated tumor necrosis factor alpha (TNF-alpha)
      production by macrophages in the Ad5IkappaB-infected liver. Moreover, the liver
      injury was completely suppressed by the administration of anti-IFN-gamma and anti
      TNF-alpha. These results suggest that inhibition of NF-kappaB activity suppressed
      alphaCD40-induced liver inflammation at an early phase, resulting in a reduction
      in cytokine and chemokine production, whereas it sensitized hepatocytes to TNF
      alpha-induced apoptosis and exacerbated liver injury at the late phase. In
      conclusion, NF-kappaB exerts pivotal activities at inflammatory sites, and
      caution should be exercised in NF-kappaB-targeted therapy of liver disease.

PMID- 15486932
TI  - Alpha-1 adrenergic receptor agonists modulate ductal secretion of BDL rats via
      Ca(2+)- and PKC-dependent stimulation of cAMP.
AB  - Acetylcholine potentiates secretin-stimulated ductal secretion by Ca(2+)
      calcineurin-mediated modulation of adenylyl cyclase. D2 dopaminergic receptor
      agonists inhibit secretin-stimulated ductal secretion via activation of protein
      kinase C (PKC)-gamma. No information exists regarding the effect of adrenergic
      receptor agonists on ductal secretion in a model of cholestasis induced by bile
      duct ligation (BDL). We evaluated the expression of alpha-1A/1C, -1beta and beta
      1 adrenergic receptors in liver sections and cholangiocytes from normal and BDL
      rats. We evaluated the effects of the alpha-1 and beta-1 adrenergic receptor
      agonists (phenylephrine and dobutamine, respectively) on bile and bicarbonate
      secretion and cholangiocyte IP(3) and Ca(2+) levels in normal and BDL rats. We
      measured the effect of phenylephrine on lumen expansion in intrahepatic bile duct
      units (IBDUs) and cyclic adenosine monophosphate (cAMP) levels in cholangiocytes
      from BDL rats in the absence or presence of BAPTA/AM and Go6976 (a PKC-alpha
      inhibitor). We evaluated if the effects of phenylephrine on ductal secretion were
      associated with translocation of PKC isoforms leading to increased protein kinase
      A activity. Alpha-1 and beta-1 adrenergic receptors were present mostly in the
      basolateral domain of cholangiocytes and, following BDL, their expression
      increased. Phenylephrine, but not dobutamine, increased secretin-stimulated
      choleresis in BDL rats. Phenylephrine did not alter basal but increased secretin
      stimulated IBDU lumen expansion and cAMP levels, which were blocked by BAPTA/AM
      and Go6976. Phenylephrine increased IP(3) and Ca(2+) levels and activated PKC
      alpha and PKC-beta-II. In conclusion, coordinated regulation of ductal secretion
      by secretin (through cAMP) and adrenergic receptor agonist activation (through
      Ca(2+)/PKC) induces maximal ductal bicarbonate secretion in liver diseases.
      (Supplementary material for this article can be found on the HEPATOLOGY website
      (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

PMID- 15486933
TI  - Quantitative screening of embryonic stem cell differentiation: endoderm formation
      as a model.
AB  - Embryonic stem (ES) cells have attracted much attention as a possible source of
      functional cells for regenerative medicine. Therapeutic use of ES cells requires
      control over the types and frequencies of cells generated during their in vitro
      differentiation. Due to the complexity of factors that impact upon ES cell
      differentiation, novel approaches for the optimization of tissue-specific
      development are required. This motivates our use of factorial and composite
      design methods to make empirical investigations more efficient, and to reveal
      unexpected interactions missed by conventional dose-response analysis. Factorial
      experiments would benefit from the high content evaluation of a large number of
      test conditions, necessitating the development of a quantitative screening
      technology (QST) capable of reporting the absolute number and frequency of target
      cells. We have developed and validated such a technology for ES cell
      differentiation analysis using automated fluorescence microscopy, employing
      endoderm differentiation as a model system. To test this platform, a two-level
      factorial experiment was carried out to identify major and interactive effects of
      glucose, insulin, retinoic acid (RA), basic fibroblast growth factor (bFGF), and
      epidermal growth factor (EGF) on endoderm formation. RA was found to have
      inhibitory effects on endoderm formation, while low glucose proved beneficial.
      QST was demonstrated to be a powerful tool to study factors impacting endoderm
      specific ES cell differentiation, and should be applicable to the analysis of a
      range of ES cell-derived tissues.

PMID- 15486934
TI  - Cryopreservation of adherent human embryonic stem cells.
AB  - Standard human embryonic stem (HES) cell cryopreservation methodologies,
      including slow freezing and vitrification of colonies in suspension, are plagued
      by poor viability and high differentiation rates upon recovery. To facilitate
      research studies and clinical applications of HES cells, we have developed a
      cryopreservation technique based on stabilizing HES colonies adherent to or
      embedded in a Matrigel matrix. This method increases cell viability by over an
      order of magnitude compared with cryopreservation in suspension and reduces
      differentiation. Loading adherent HES cells with the disaccharide trehalose prior
      to cryopreserving in a dimethylsulfoxide-containing cryoprotectant solution
      further improves cell viability under certain conditions. Our proposed approach
      has the potential to reduce the time required to amplify frozen stocks of HES
      cells, minimize risk of clonal selection during freeze-thaw cycles, and
      facilitate storage of HES cell clone libraries.

PMID- 15486935
TI  - Three-dimensional porous alginate scaffolds provide a conducive environment for
      generation of well-vascularized embryoid bodies from human embryonic stem cells.
AB  - Differentiation of human embryonic stem cells (hESCs) can be instigated through
      the formation of embryo-like aggregates in suspension, termed human embryoid
      bodies (hEBs). Controlling cell aggregation and agglomeration during hEBs
      formation has a profound effect on the extent of cell proliferation and
      differentiation. In a previous work, we showed that control over hEBs formation
      and differentiation can be achieved via cultivation of hESC suspensions in a
      rotating bioreactor system. We now report that hEBs can be generated directly
      from hESC suspensions within three-dimensional (3D) porous alginate scaffolds.
      The confining environments of the alginate scaffold pores enabled efficient
      formation of hEBs with a relatively high degree of cell proliferation and
      differentiation; encouraged round, small-sized hEBs; and induced vasculogenesis
      in the forming hEBs to a greater extent than in static or rotating cultures. We
      therefore conclude that differentiation of hEBs can be induced and directed by
      physical constraints in addition to chemical cues.

PMID- 15486936
TI  - Concanavalin a injection activates intrahepatic innate immune cells to provoke an
      antitumor effect in murine liver.
AB  - Concanavalin A (ConA), directly injected into mice, induces T cell-mediated liver
      injury. However, it remains unclear whether ConA injection can activate innate
      immune cells, including natural killer (NK) cells and natural killer T (NKT)
      cells, both of which exist abundantly in the liver. Here we report that ConA
      injection stimulated interferon (IFN)-gamma production from liver NKT cells as
      early as 2 hours after injection and augmented YAC-1 cytotoxicity of liver NK
      cells. ConA-induced NK cell activation required other types of immune cells and
      critically depended on IFN-gamma. Because a nonhepatotoxic low dose of ConA was
      capable of fully activating both NKT cells and NK cells, we next addressed the
      possibility of ConA injection displaying an antitumor effect in the liver without
      liver injury. A nonhepatotoxic low-dose ConA injection augmented the cytotoxicity
      of liver NK cells against Colon-26 colon cancer cells and suppressed hepatic
      metastasis of Colon-26 cells in a NK cell- and IFN-gamma-dependent manner. In
      conclusion, a nonhepatotoxic low dose of ConA might serve as an immunomodulator
      that can preferentially activate the innate immune cells to induce an antitumor
      effect against metastatic liver tumor.

PMID- 15486937
TI  - A novel mechanism of liver allograft rejection facilitated by antibodies to liver
      sinusoidal endothelial cells.
AB  - Liver sinusoidal endothelial cells (LSECs) may be implicated in the induction of
      liver allograft rejections. We studied the clinical consequences of LSEC-reactive
      antibodies and their functional capacity in modulating T-cell responses during
      acute rejections. Pre- and posttransplant sera and T lymphocytes from 95 liver
      transplant patients were used in this study. LSECs were isolated from normal
      healthy liver. Binding of antibodies to LSECs was detected using flow cytometry.
      To study whether LSEC antibodies facilitated cell-mediated immunity, a mixed cell
      culture (MCC) assay was used. Cytokines in the supernatants of MCC were measured
      by enzyme-linked immunosorbent assay. Liver biopsy sections were stained to
      detect the deposition of immunoglobulins in LSECs during rejections. The 2-year
      patient survival was 86.3%. A significantly higher number of patients with
      rejections had LSEC antibodies (35/50; 70%) than those without rejections (8/45;
      18%) (P < .0001). Purified fractions of LSEC antibodies induced the expression of
      the costimulatory molecule CD86 on LSECs. A significantly higher number of
      patients with LSEC antibodies and rejections had an increased proliferation of T
      cells and markedly decreased levels of transforming growth factor beta (TGF-beta)
      in the MCC than those without antibodies and rejections (P < .0001, P < .0001,
      respectively). Deposition of antibodies in LSECs during rejection episodes was
      observed in the biopsies of patients with LSEC antibodies but not in those
      without LSEC antibodies. In conclusion, antibodies to LSECs may facilitate acute
      liver allograft rejections by down-regulating the immune modulating cytokine TGF
      beta and thus up-regulating alloreactive T-cell proliferation.

PMID- 15486938
TI  - Differential detection of PAS-positive inclusions formed by the Z, Siiyama, and
      Mmalton variants of alpha1-antitrypsin.
AB  - Several point mutations of alpha(1)-antitrypsin cause a perturbation in protein
      structure with consequent polymerization and intracellular accumulation. The
      retention of polymers of alpha(1)-antitrypsin within hepatocytes results in
      protein overload that in turn is associated with juvenile hepatitis, cirrhosis,
      and hepatocellular carcinoma. The detection of alpha(1)-antitrypsin polymers and
      understanding the molecular basis of polymer formation is of considerable
      clinical importance. We have used a monoclonal antibody (ATZ11) that specifically
      recognizes a conformation-dependent neoepitope on polymerized alpha(1)
      antitrypsin to detect polymers within hepatocytes of individuals with alpha(1)
      antitrypsin deficiency. Paraffin-embedded liver tissue specimens were obtained
      from individuals who were homozygous for the Z (Glu342Lys), Mmalton (52Phe del),
      and Siiyama (Ser53Phe) alleles of alpha(1)-antitrypsin that result in hepatic
      inclusions and profound plasma deficiency. Immunohistological staining with a
      polyclonal anti-human alpha(1)-antitrypsin antibody showed hepatic inclusions in
      all 3 cases, while ATZ11 reacted with hepatic inclusions formed by only Z
      alpha(1)-antitrypsin. Polymers of plasma M and Z alpha(1)-antitrypsin prepared
      under different conditions in vitro and polymers of recombinant mutants of
      alpha(1)-antitrypsin demonstrated that the monoclonal antibody detected a
      neoepitope on the polymerized protein. It did not detect polymers formed by a
      recombinant shutter domain mutant (that mirrors the effects of the Siiyama and
      Mmalton variants), polymers formed by cleaving alpha(1)-antitrypsin at the
      reactive loop, or C-sheet polymers formed by heating alpha(1)-antitrypsin in
      citrate. In conclusion, the ATZ11 monoclonal antibody detects Z alpha(1)
      antitrypsin in hepatic inclusions by detecting a neoepitope that is specific to
      the polymeric conformer and that is localized close to residue 342.

PMID- 15486939
TI  - Expansion of pluripotent human embryonic stem cells on human feeders.
AB  - Human embryonic stem cells (HES) hold great potential for regenerative medicine
      because of their ability to differentiate to any cell type. However, a limitation
      is that HES cells require a feeder layer to stay undifferentiated. Routinely,
      mouse embryonic fibroblast is used. However, for therapeutic applications,
      contamination with mouse cells may be considered unacceptable. In this study, we
      evaluated three commercially available human foreskin feeder (HF) lines for their
      ability to support HES cell growth in media supplemented with serum or serum
      replacer. HES cells on HF in serum replacer-supplemented media were cultured for
      >30 passages. They remained undifferentiated, maintained a normal karyotype, and
      continued to be positive for the pluripotent markers Oct-4, SOX-2, SSEA-4, GCTM
      2, Tra-1-60, Tra-1-81, and alkaline phosphatase. In vivo, HES cells formed
      teratomas in SCID mouse models that represent the three embryonic germ layers. In
      contrast, HES cells cultured on HF in serum-supplemented media differentiated
      after three passages. Morphologically, the cells became cystic with a loss of
      intracellular Oct-4. We have successfully adapted and cultured undifferentiated
      HES cells on three human feeder lines for >30 passages. No difficulties were
      observed with the exception of serum in the media. This study reveals a safe and
      accessible source for feeders for HES cell research and potential therapeutic
      applications.

PMID- 15486940
TI  - Cell cycle kinetics of expanding populations of neural stem and progenitor cells
      in vitro.
AB  - Neural stem cells (NSCs) are undifferentiated, primitive cells with important
      potential applications including the replacement of neural tissue lost due to
      neurodegenerative diseases, including Parkinson's disease, as well as brain and
      spinal cord injuries, including stroke. We have developed methods to rapidly
      expand populations of mammalian stem and progenitor cells in neurosphere
      cultures. In the present study, flow cytometry was used in order to understand
      cell cycle activation and proliferation of neural stem and progenitor cells in
      suspension bioreactors. First, a protocol was developed to analyze the cell cycle
      kinetics of NSCs. As expected, neurosphere cells were found to cycle slowly, with
      a very small proportion of the cell population undergoing mitosis at any time.
      Large fractions (65-70%) of the cells were detected in G1, even in rapidly
      proliferating cultures, and significant fractions (20%) of the cells were in G0.
      Second, it was observed that different culturing methods influence both the
      proportion of neurosphere cells in each phase of the cell cycle and the fraction
      of actively proliferating cells. The results show that suspension culture does
      not significantly alter the cell cycle progression of neurosphere cells, while
      long-term culture (>60 days) results in significant changes in cell cycle
      kinetics. This suggests that when developing a process to produce neural stem
      cells for clinical applications, it is imperative to track the cell cycle
      kinetics, and that a short-term suspension bioreactor process can be used to
      successfully expand neurosphere cells.

PMID- 15486941
TI  - Empirical models of the proliferative response of cytokine-dependent
      hematopoietic cell lines.
AB  - There is an expanding need for predictive mathematical models to accelerate the
      optimization of cell therapy culture processes. Here we demonstrate the ability
      of simple mathematical models to describe quantitatively the cytokine growth-rate
      dependence of two human hematopoietic cell lines, TF-1 and MO7e. These cells are
      immortal but depend on either interleukin-3 (IL-3) or granulocyte-macrophage
      colony stimulating factor (GM-CSF) for their continued survival and maximal
      proliferation. They are also responsive to interleukin-6 (IL-6) and exhibit
      saturation kinetics when these cytokines are limiting. A Monod-type relationship
      consistently failed to fit measured cytokine dose-proliferation response curves
      while a Hill-type relationship showed a good fit. Cytokine interactions were
      first modeled by modifying the Hill-function to include an interaction parameter,
      gamma. This model did not indicate either synergistic or even additive effects
      between IL-3 and GM-CSF. Based on the reported competition between IL-3 and GM
      CSF for their common receptor (beta(c)) subunit, a competitive model was also
      developed. This model had no new parameters beyond those obtained from single
      cytokine cultures and provided improved prediction of the growth rates for both
      cell lines exposed to combinations of IL-3 and GM-CSF over a wide range of
      concentrations. As expected, the competitive model failed to fit the data for IL
      6 in combination with either IL-3 or GM-CSF, since IL-6 signaling does not
      involve the beta(c) chain of the IL-3/GM-CSF receptors. Interestingly, the cell
      specific rates of GM-CSF uptake and cell proliferation were found to be uncoupled
      processes. Taken together, these results illustrate the utility of appropriately
      designed empirical models to describe the proliferative responses of
      hematopoietic cells to cytokine stimulation.

PMID- 15486942
TI  - Differential effects of equiaxial and uniaxial strain on mesenchymal stem cells.
AB  - Bone marrow mesenchymal stem cells (MSCs) can differentiate into a variety of
      cell types, including vascular smooth muscle cells (SMCs), and have tremendous
      potential as a cell source for cardiovascular regeneration. We postulate that
      specific vascular environmental factors will promote MSC differentiation into
      SMCs. However, the effects of the vascular mechanical environment on MSCs have
      not been characterized. Here we show that mechanical strain regulated the
      expression of SMC markers in MSCs. Cyclic equiaxial strain downregulated SM alpha
      actin and SM-22alpha in MSCs on collagen- or elastin-coated membranes after 1
      day, and decreased alpha-actin in stress fibers. In contrast, cyclic uniaxial
      strain transiently increased the expression of SM alpha-actin and SM-22alpha
      after 1 day, which subsequently returned to basal levels after the cells aligned
      in the direction perpendicular to the strain direction. In addition, uniaxial but
      not equiaxial strain induced a transient increase of collagen I expression. DNA
      microarray experiments showed that uniaxial strain increased SMC markers and
      regulated the expression of matrix molecules without significantly changing the
      expression of the differentiation markers (e.g., alkaline phosphatase and
      collagen II) of other cell types. Our results suggest that uniaxial strain, which
      better mimics the type of mechanical strain experienced by SMCs, may promote MSC
      differentiation into SMCs if cell orientation can be controlled. This study
      demonstrates the differential effects of equiaxial and uniaxial strain, advances
      our understanding of the mechanical regulation of stem cells, and provides a
      rational basis for engineering MSCs for vascular tissue engineering and
      regeneration.

PMID- 15486943
TI  - Runx2/Cbfa1-genetically engineered skeletal myoblasts mineralize collagen
      scaffolds in vitro.
AB  - Genetic engineering of progenitor and stem cells is an attractive approach to
      address cell sourcing limitations associated with tissue engineering
      applications. Bone tissue engineering represents a promising strategy to repair
      large bone defects, but has been limited in part by the availability of a
      sustained, mineralizing cell source. This study examined the in vitro
      mineralization potential of primary skeletal myoblasts genetically engineered to
      overexpress Runx2/Cbfa1, an osteoblastic transcriptional regulator essential to
      bone formation. These cells were viable at the periphery of 3D fibrous collagen
      scaffolds for 6 weeks of static culture. Exogenous Runx2 expression induced
      osteogenic differentiation and repressed myogenesis in these constructs relative
      to controls. Runx2-modified cells deposited significant amounts of mineralized
      matrix and hydroxyapatite, as determined by microcomputed tomography,
      histological analysis, and Fourier transform infrared spectroscopy, whereas
      scaffolds seeded with control cells exhibited no mineralized regions. Although
      mineralization by Runx2-engineered cells was confined to the periphery of the
      construct, colocalizing with cell viability, it was sufficient to increase the
      compressive modulus of constructs 30-fold relative to controls. This work
      demonstrates that Runx2 overexpression in skeletal myoblasts may address current
      obstacles of bone tissue engineering by providing a potent cell source for in
      vitro mineralization and construct maturation. Additionally, the use of genetic
      engineering methods to express downstream control factors and transcriptional
      regulators, in contrast to soluble signaling molecules, represents a robust
      strategy to enhance cellular activities for tissue engineering applications.

PMID- 15486944
TI  - Engineering cartilage-like tissue using human mesenchymal stem cells and silk
      protein scaffolds.
AB  - Human mesenchymal stem cells (hMSC) derived from bone marrow aspirates can form
      the basis for the in vitro cultivation of autologous tissue grafts and help
      alleviate the problems of immunorejection and disease transmission associated
      with the use of allografts. We explored the utility of hMSC cultured on protein
      scaffolds for tissue engineering of cartilage. hMSC were isolated, expanded in
      culture, characterized with respect to the expression of surface markers and
      ability for chondrogenic and osteogenic differentiation, and seeded on scaffolds.
      Four different scaffolds were tested, formed as a highly porous sponge made of:
      1) collagen, 2) cross-linked collagen, 3) silk, and 4) RGD-coupled silk. Cell
      seeded scaffolds were cultured for up to 4 weeks in either control medium (DMEM
      supplemented with 10% fetal bovine serum) or chondrogenic medium (control medium
      supplemented with chondrogenic factors). hMSC attachment, proliferation, and
      metabolic activity were markedly better on slowly degrading silk than on fast
      degrading collagen scaffolds. In chondrogenic medium, hMSC formed cartilaginous
      tissues on all scaffolds, but the extent of chondrogenesis was substantially
      higher for hMSC cultured on silk as compared to collagen scaffolds. The
      deposition of glycosaminoglycan (GAG) and type II collagen and the expression of
      type II collagen mRNA were all higher for hMSC cultured on silk than on collagen
      scaffolds. Taken together, these results suggest that silk scaffolds are
      particularly suitable for tissue engineering of cartilage starting from hMSC,
      presumably due to their high porosity, slow biodegradation, and structural
      integrity.

PMID- 15486945
TI  - Quartz crystal microbalance-based measurements of shear-induced senescence in
      human embryonic kidney cells.
AB  - Fluid shear and other mechanical forces play an important role in the normal
      biophysical, biochemical, and gene regulatory responses of vertebrate tissue that
      are reflected in the expression of normal cell differentiation, growth, and
      function. Despite some promising work reported on the application of the quartz
      crystal microbalance (QCM) to both prokaryote and eukaryote cells over the last
      decade, QCM has yet to be successfully applied to cells in culture under
      conditions of flow-induced shear. In this study, high sensitivity QCM in
      conjunction with fluid modelling was used to monitor the onset of senescence in
      immortalised human embryonic kidney cells under laminar shear stresses of between
      0.04 and 335 dyne/cm(2). The feasibility of this approach as a means of
      quantification and characterisation of cell physiological response and adhesion
      are explored and discussed.

PMID- 15486946
TI  - Microfabricated platform for studying stem cell fates.
AB  - Platforms that allow parallel, quantitative analysis of single cells will be
      integral to realizing the potential of postgenomic biology. In stem cell biology,
      the study of clonal stem cells in multiwell formats is currently both inefficient
      and time-consuming. Thus, to investigate low-frequency events of interest, large
      sample sizes must be interrogated. We report a simple, versatile, and efficient
      micropatterned arraying system conducive to the culture and dynamic monitoring of
      stem cell proliferation. This platform enables: 1) parallel, automated, long-term
      ( approximately days to weeks), live-cell microscopy of single cells in culture;
      2) tracking of individual cell fates over time (proliferation, apoptosis); and 3)
      correlation of differentiated progeny with founder clones. To achieve these
      goals, we used microfabrication techniques to create an array of approximately
      10,000 microwells on a glass coverslip. The dimensions of the wells are tunable,
      ranging from 20 to >500 microm in diameter and 10-500 microm in height. The
      microarray can be coated with adhesive proteins and is integrated into a culture
      chamber that permits rapid (approximately min), addressable monitoring of each
      well using a standard programmable microscope stage. All cells share the same
      media (including paracrine survival signals), as opposed to cells in multiwell
      formats. The incorporation of a coverslip as a substrate also renders the
      platform compatible with conventional, high-magnification light and fluorescent
      microscopy. We validated this approach by analyzing the proliferation dynamics of
      a heterogeneous adult rat neural stem cell population. Using this platform, one
      can further interrogate the response of distinct stem cell subpopulations to
      microenvironmental cues (mitogens, cell-cell interactions, and cell-extracellular
      matrix interactions) that govern their behavior. In the future, the platform may
      also be adapted for the study of other cell types by tailoring the surface
      coatings, microwell dimensions, and culture environment, thereby enabling
      parallel investigation of many distinct cellular responses.

PMID- 15486947
TI  - In vivo mutational analysis of liver DNA in gpt delta transgenic rats treated
      with the hepatocarcinogens N-nitrosopyrrolidine, 2-amino-3-methylimidazo[4,5
      f]quinoline, and di(2-ethylhexyl)phthalate.
AB  - In order to cast light on carcinogen-specific molecular mechanisms underlying
      experimental hepatocarcinogenesis in rats, in vivo mutagenicity and mutation
      spectra of known genotoxic rat hepatocarcinogens N-nitrosopyrrolidine (NPYR), and
      2-amino-3-methylimidazo[4,5-f]quinoline (IQ), as well as the nongenotoxic
      hepatocarcinogen di(2-ethylhexyl)phthalate (DEHP) and the noncarcinogen
      acetaminophen (AAP), were investigated in guanine phosphoribosyltransferase (gpt)
      delta transgenic rats, a recently developed animal model for genotoxicity
      analysis. After 13-wk treatment, glutathione S-transferase placental form (GST-P)
      positive liver cell foci were significantly increased in NPYR-treated and IQ
      treated rats. In the DEHP-treated rats, marked hepatomegaly with centrilobular
      hypertrophy of hepatocytes occurred, although GST-P staining was consistently
      negative. Positive mutagenicity was detected in IQ- and NPYR-treated rats. Mutant
      frequencies (MFs) in the liver DNA were 188.0 x 10(-6) and 56.5 x 10(-6),
      approximately 35-fold and 10-fold higher, respectively, than that of nontreatment
      control rats (5.5 x 10(-6)). There were no increases in MFs in the DEHP- or AAP
      treated rats as compared to the nontreatment control value. IQ induced mainly
      base substitutions leading to G:C to T:A transversions (56.9%) and deletions of
      G:C base pairs. In contrast, NPYR primarily caused specific A:T to G:C
      transitions (49.3%), which are very rare in the other groups. These data provided
      support for the conclusion that IQ and NPYR hepatocarcinogenesis depends on
      genotoxic processes and specific DNA adduct formation while DEHP exerts its
      influence via a nongenotoxic promotional pathway. Our data also indicate that
      analysis of specific in vivo mutational responses with transgenic animal models
      can provide crucial information for understanding the molecular mechanisms
      underlying chemical carcinogenesis.

PMID- 15486948
TI  - How do you stretch a bladder? A survey of UK practice, a literature review, and a
      recommendation of a standard approach.
AB  - AIMS: To assess how and why hydrodistension of the bladder is performed by UK
      urologists and to compare this practise with the published literature on
      distension. To suggest a standardised technique for hydrodistension to allow
      comparison of diagnostic and therapeutic studies. METHODS: A questionnaire was
      sent to all UK consultant urologists. Questions addressed the indications for
      short bladder distension (SBD), details of technique, evaluation of outcome, and
      awareness of evidence base. The literature on bladder distension was reviewed.
      RESULTS: The majority of respondents perform SBD, principally in the diagnosis
      and therapy of interstitial cystitis (IC). There was considerable variation in
      the duration of distension, repetition of distension, the pressure used for
      distension, and the measurement of bladder capacity. The literature on the
      technique of hydrodistension is imprecise and no respondent was able to cite
      literature to support his or her practice. We suggest a simple, more objective
      technique for performing hydrodistension. CONCLUSIONS: SBD is widely used. There
      is marked variability in technique and little more than anecdotal evidence to
      support any particular approach. Research into the evaluation and treatment of
      painful bladder syndrome in general and IC in particular would be facilitated by
      the adoption of a standardised technique.

PMID- 15486949
TI  - First report of overactive detrusor in association with hypospadias detected by
      urodynamic screening.
AB  - AIMS: The purpose of this study was to determine urodynamic features in
      hypospadic patients. METHODS: Thirty-seven patients with hypospadias (distal: 31,
      proximal: 6) underwent preoperative urodynamic study according to International
      Continence Society (ICS) recommendations. Statistical analysis were done for
      comparison between urethral obstruction and non-obstruction in patients with
      detrusor overactivity (DO) plus the relationship of DO with localization of
      hipospadias. RESULTS: Nearly 45.9% of the patients showed overactive detrusor.
      Urethral obstruction was found in 60.8% of the patients. The rate of DO was
      higher in proximal hipospadias, and urethral obstruction than distal type, and
      non-obstructed patients (P > 0.005). The means overall cystometric capacity,
      maximum voiding detrusor pressure and maximal urinary flow measured were 132.6 +/
      111.14 ml (range 21-610), 72 +/- 53 cmH2O (range 12-181), and 7.9 +/- 7.1 ml/sec
      (range 2-30 ml/sec), respectively. CONCLUSIONS: To the best of our knowledge,
      this is the first study ever to show that overactive detrusor is an accompanying
      entity in the hypospadic patients.

PMID- 15486950
TI  - Microdissection and SAGE as a combined tool to reveal gene expression in ductal
      carcinoma in situ of the breast.
AB  - The interplay between cancer cells and the normal surrounding tissue is believed
      to influence the biological behavior of the tumor. However, the presence of
      multiple cell types within the prelevated tumor specimen may attenuate changes
      that occur specifically in the malignant cells within their microenvironment. To
      study gene expression of the malignant cells in situ, we used a new
      microdissection method to separate ductal carcinoma in situ (DCIS) cells from the
      surrounding stroma, immunological infiltrates, and endothelial cells. We applied
      an adapted microSAGE protocol, without total mRNA amplification, to study their
      gene expression profile. Three thousand two hundred one different transcripts
      were identified in a total of 29 534 observed tags. Of these unique tags, 88.3%
      matched known GenBank sequences and 11.7% represented unknown transcripts. As
      compared to a total DCIS SAGE library, microdissection combined with SAGE
      revealed additional genes expressed only in normal surrounding, probably stromal,
      cells and not or significantly less in DCIS tumor cells. This study demonstrates
      that microdissection can be combined with SAGE as a tool to study transcriptomes.
      This approach provides important new information on differential gene expression
      both in tumor cells and normal surrounding tissue. Several of the observed
      differences indeed disappear when the total tumor mass is analyzed.

PMID- 15486951
TI  - A young girl with hemolytic anemia and elevated hemoglobin F.
AB  - The non-immune, non-spherocytic anemias result from multiple potential
      etiologies. We report a 16-year-old girl, who was presented with a long-standing
      anemia and normal blood screening tests except an elevated hemoglobin F. Her
      diagnosis of unstable hemoglobinopathy was made only after gene sequencing of the
      beta-globin chain.

PMID- 15486952
TI  - Delays in diagnosis and treatment of childhood cancer: where in the world are
      they important?

PMID- 15486953
TI  - Down syndrome and leukemia: new insights into the epidemiology, pathogenesis, and
      treatment.

PMID- 15486954
TI  - Neuroanatomy of the killer whale (Orcinus orca) from magnetic resonance images.
AB  - This article presents the first series of MRI-based anatomically labeled
      sectioned images of the brain of the killer whale (Orcinus orca). Magnetic
      resonance images of the brain of an adult killer whale were acquired in the
      coronal and axial planes. The gross morphology of the killer whale brain is
      comparable in some respects to that of other odontocete brains, including the
      unusual spatial arrangement of midbrain structures. There are also intriguing
      differences. Cerebral hemispheres appear extremely convoluted and, in contrast to
      smaller cetacean species, the killer whale brain possesses an exceptional degree
      of cortical elaboration in the insular cortex, temporal operculum, and the
      cortical limbic lobe. The functional and evolutionary implications of these
      features are discussed.

PMID- 15486955
TI  - Three-dimensional arrangement of the vasa vasorum in explanted segments of the
      aged human great saphenous vein: scanning electron microscopy and three
      dimensional morphometry of vascular corrosion casts.
AB  - The vasa vasorum of skeletonized and nonskeletonized segments of five human great
      saphenous veins (GSVs), harvested during coronary bypass grafting, were
      cannulated, rinsed, and injected (casted) with the polymerizing resin Mercox-Cl
      2B. After removal of the dry vascular tissue, the casts were examined using
      scanning electron microscopy. Stereopaired images (tilt angle, 6 degrees ) were
      taken, imported into a 3D morphometry system, and the 3D architecture of the vasa
      vasorum (arterial and venous vasa as well as capillaries) was studied
      qualitatively and quantitatively in terms of vasa diameters, intervascular and
      interbranching distances, and branching angles. Diameters of parent (d(0)) and
      large (d(1)) and small (d(2)) daughter vessels of arterial and venous
      bifurcations served to calculate asymmetry ratios (alpha) and area ratios (beta).
      Additionally, deviations of bifurcations and branching angles from optimal
      branches were calculated for selected arterial vasa. The arrangement of the vasa
      vasorum closely followed the longitudinally oriented connective tissue fibers in
      the adventitia and the circularly arranged smooth muscle cell layers within the
      outer layers of the media. Venous vasa by far outnumbered arterial vasa. Vasa
      vasorum changed their course several times in acute angles and revealed numerous
      circular constrictions, kinks, and outpouchings. Due to their spatial
      arrangement, the vasa vasorum are prone to tolerate vessel wall distension
      generated by acute increases in blood pressure or stretching of the vessel
      without severe impact on vessel functions. Preliminary comparisons of data from
      the bifurcations of cast arterial vasa vasorum, with calculated optimal
      bifurcations, do not yet give clear insights into the optimality principle(s)
      governing the design of arterial vasa vasorum bifurcations of the human GSVs.

PMID- 15486956
TI  - ANT2 expression under hypoxic conditions produces opposite cell-cycle behavior in
      143B and HepG2 cancer cells.
AB  - Under hypoxic conditions, mitochondrial ATP production ceases, leaving cells
      entirely dependent on their glycolytic metabolism. The cytoplasmic and
      intramitochondrial ATP/ADP ratios, partly controlled by the adenine nucleotide
      translocator (ANT), are drastically modified. In dividing and growing cells that
      have a predominantly glycolytic metabolism, the ANT isoform 2, which has kinetic
      properties allowing ATP import into mitochondria, is over-expressed in comparison
      to control cells. We studied the cellular metabolic and proliferative response to
      hypoxia in two transformed human cell lines with different metabolic backgrounds:
      HepG2 and 143B, and in their rho(o) derivatives, i.e., cells with no
      mitochondrial DNA. Transformed 143B and rho(o) cells continued their
      proliferation whereas HepG2 cells, with a more differentiated phenotype, arrested
      their cell-cycle at the G(1)/S checkpoint. Hypoxia induced an increase in
      glycolytic activity, correlated to an induction of VEGF and hexokinase II (HK II)
      expression. Thus, according to their tumorigenicity, transformed cells may adopt
      one of two distinct behaviors to support hypoxic stress, i.e., proliferation or
      quiescence. Our study links the constitutive glycolytic activity and ANT2
      expression levels of transformed cells with the loss of cell-cycle control after
      oxygen deprivation. ATP import by ANT2 allows cells to maintain their
      mitochondrial integrity while acquiring insensitivity to any alterations in the
      proteins involved in oxidative phosphorylation. This loss of cell dependence on
      oxidative metabolism is an important factor in the development of tumors.

PMID- 15486957
TI  - Industry guidelines, laws and regulations ignored: quality of drug advertising in
      medical journals.
AB  - PURPOSE: To document the quality of evidence base for marketing claims in
      prescription drug advertisements, to facilitate identification of potential
      targets for quality improvement. METHODS: A sample of 1036 advertisements from
      four major Finnish medical journals published in 2002. Marketing claims were
      classified in four groups: unambiguous clinical outcome, vague clinical outcome,
      emotive or immeasurable outcome and non-clinical outcome. Medline references were
      traced and classified according to the level of evidence available. The
      statistical variables used in the advertisements were also documented. RESULTS:
      The sample included 245 distinct advertisements with 883 marketing claims, 1-10
      claims per advertisement. Three hundred thirty seven (38%) of the claims were
      referenced. Each claim could be supported by one reference or more, so the number
      of references analysed totalled 381, 1-9 references per advertisement. Nine
      percent of the claims implied unambiguous clinical outcomes, 68% included vague
      or emotive statements. Twenty one percent of the references were irrelevant to
      the claim. There was a fair amount of non-scientific and scientific support for
      the 73 unambiguous claims, but not a single claim was supported by strong
      scientific evidence. Vague, emotive and non-clinical claims were significantly
      more often supported by non-Medline or irrelevant references than unambiguous
      claims. Statistical parameters were stated only 34 times. CONCLUSION: Referenced
      marketing claims may appear more scientific, but the use of references does not
      guarantee the quality of the claims. For the benefit of all stakeholders, both
      the regulatory control and industry's self-control of drug marketing should adopt
      more active monitoring roles, and apply sanctions when appropriate. Concerted
      efforts by several stakeholders might be more effective.

PMID- 15486958
TI  - Pharmaceutical advertising: fact or fiction?

PMID- 15486959
TI  - The need for a population-based surveillance system for liver disease in the
      United States.

PMID- 15486960
TI  - Quetiapine has a direct effect on the negative symptoms of schizophrenia.
AB  - Second-generation 'atypical' antipsychotics appear to be more effective than
      first-generation 'typical' antipsychotics in improving negative symptoms in
      schizophrenia; it is unclear, however, if this greater improvement represents a
      direct beneficial effect or is mediated indirectly by an antidepressant effect or
      the absence of extrapyramidal symptoms (EPS). To address this issue with
      reference to quetiapine ('Seroquel'), data were evaluated from four randomized,
      controlled clinical studies involving 1106 patients employing a path analysis
      model. The total effect of quetiapine on negative symptoms was measured using the
      Scale for Assessment of Negative Symptoms (SANS) total score. Indirect effects on
      negative symptoms via positive, depressive and EPS were assessed using
      appropriate instruments. Effect sizes were calculated by path analysis for the
      difference between treatment groups in change from baseline to endpoint in SANS
      total score. Analysis confirmed that quetiapine produced a greater overall
      improvement in negative symptoms than placebo (effect size 1.96); this was
      explained by a significant direct effect (p = 0.001; 44.2% of total improvement),
      and a secondary effect of improved positive symptoms (p < 0.001; 47.5% of total
      improvement), but was not a consequence of changes in depressive symptoms or EPS.
      Within the constraints of the path analysis methodology, these results indicate
      that quetiapine has a substantial direct effect on improving the negative
      symptoms of schizophrenia.

PMID- 15486961
TI  - The impact of glucose ingestion and gluco-regulatory control on cognitive
      performance: a comparison of younger and middle aged adults.
AB  - A great deal of research has been devoted to the issue of whether the ingestion
      of a glucose containing drink facilitates cognitive performance. However, it
      remains unclear exactly how age and individual differences in gluco-regulatory
      control mediate a boost in cognitive functioning. The present study investigates
      these issues further. A repeated measures (25 g vs 50 g glucose vs placebo)
      counterbalanced, double-blind design was used with 25 younger and middle-aged
      adults. A battery of memory and non-memory tasks was administered; including
      tests of episodic and semantic memory, attention and visuospatial functioning.
      Glucose ingestion largely facilitated performance on tasks with a memory
      component. Notably, task demands and age (young vs middle-aged) contributed to
      the magnitude of memory enhancement. This finding suggests an age- and load
      specific benefit of glucose intake. In addition, evidence suggests greater
      facilitation in individuals with good glucose regulation. These data are
      discussed in relation to the idea that glucose specifically affects neural
      mechanisms supporting memory functioning (i.e. the hippocampus), which are known
      to decline in ageing. Importantly, the present investigation adds to the growing
      body of literature showing the utility of glucose supplementation as memory
      enhancers.

PMID- 15486962
TI  - Iatrogenic molar borings in 18th and early 19th century Native American
      dentitions.
AB  - Six iatrogenic dental borings were identified in four individuals of a Native
      American skeletal collection from an 18th and early 19th century Middle Columbia
      River burial site. The borings, all in maxillary first molars with severe dental
      attrition and secondary dentin, demonstrate striated walls and associated
      periapical alveolar lesions. An ethnographic review of the subsistence pattern
      during the burial period indicates a diet that is consistent in dental attrition
      with other riverine fisher-hunter-gathers. Histological changes of dental pulp
      tissue during the process of attrition may result in dental necrosis. Access into
      the pulp chamber is a technique used to drain necrotic fluid. A common Euro
      American therapeutic dental practice of the 18th and 19th centuries for diseases
      of the pulp was dental extraction. Multiple dental borings indicate that the
      practice of molar drilling into the pulp chamber was an effective and independent
      technique used by the Wishram and Wasco people.

PMID- 15486963
TI  - Cooperative effect of biliverdin and carbon monoxide on survival of mice in
      immune-mediated liver injury.
AB  - Induction of the heme-degrading enzyme heme oxygenase-1 (HO-1) has been shown to
      be beneficial in terms of improvement of liver allograft survival and prevention
      of CD95-mediated apoptosis in the liver. In the present study, we investigated
      the effects of HO-1, and its products carbon monoxide (CO), biliverdin (BV), and
      iron/ferritin, in a mouse model of inflammatory liver damage inducible by
      lipopolysaccharide (LPS) in mice sensitized with the hepatocyte-specific
      transcription inhibitor D-galactosamine (GalN). Our results show that HO-1
      induction by cobalt-protoporphyrin-IX (CoPP) reduced cytokine expression,
      protected mice from liver injury, and prolonged survival. While in contrast to
      ferritin overexpression, single administration of the CO donor methylene chloride
      (MC) or of BV also protected mice from liver damage, only coadministration of
      both HO products prolonged survival and reduced the expression of cytokines,
      e.g., tumor necrosis factor (TNF) and interferon gamma (IFN-gamma). In
      conclusion, HO-1-induced prolongation of survival, but not the protection from
      liver damage, seems to be dependent on down-regulation of cytokine synthesis.

PMID- 15486964
TI  - Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult
      human mesenchymal stem cells.
AB  - Multipotential adult mesenchymal stem cells (MSCs) are able to differentiate
      along several known lineages, and lineage commitment is tightly regulated through
      specific cellular mediators and interactions. Recent observations of a low/high
      bone-mass phenotype in patients expressing a loss-/gain-of-function mutation in
      LRP5, a coreceptor of the Wnt family of signaling molecules, suggest the
      importance of Wnt signaling in bone formation, possibly involving MSCs. To
      analyze the role of Wnt signaling in mesenchymal osteogenesis, we have profiled
      the expression of WNTs and their receptors, FRIZZLEDs (FZDs), and several
      secreted Wnt inhibitors, such as SFRPs, and examined the effect of Wnt 3a, as a
      representative canonical Wnt member, during MSC osteogenesis in vitro. WNT11,
      FZD6, SFRP2, and SFRP3 are upregulated during MSC osteogenesis, while WNT9A and
      FZD7 are downregulated. MSCs also respond to exogenous Wnt 3a, based on increased
      beta-catenin nuclearization and activation of a Wnt-responsive promoter, and the
      magnitude of this response depends on the MSC differentiation state. Wnt 3a
      exposure inhibits MSC osteogenic differentiation, with decreased matrix
      mineralization and reduced alkaline phosphatase mRNA and activity. Wnt 3a
      treatment of fully osteogenically differentiated MSCs also suppresses
      osteoblastic marker gene expression. The Wnt 3a effect is accompanied by
      increased cell number, resulting from both increased proliferation and decreased
      apoptosis, particularly during expansion of undifferentiated MSCs. The osteo
      suppressive effects of Wnt 3a are fully reversible, i.e., treatment prior to
      osteogenic induction does not compromise subsequent MSC osteogenesis. The results
      also showed that sFRP3 treatment attenuates some of the observed Wnt 3a effects
      on MSCs, and that inhibition of canonical Wnt signaling using a dominant negative
      TCF1 enhances MSC osteogenesis. Interestingly, expression of Wnt 5a, a non
      canonical Wnt member, appeared to promote osteogenesis. Taken together, these
      findings suggest that canonical Wnt signaling functions in maintaining an
      undifferentiated, proliferating progenitor MSC population, whereas non-canonical
      Wnts facilitate osteogenic differentiation. Release from canonical Wnt regulation
      is a prerequisite for MSC differentiation. Thus, loss-/gain-of-function mutations
      of LRP5 would perturb Wnt signaling and depress/promote bone formation by
      affecting the progenitor cell pool. Elucidating Wnt regulation of MSC
      differentiation is important for their potential application in tissue
      regeneration.

PMID- 15486965
TI  - Jaw-muscle electromyography during chewing in Belanger's treeshrews (Tupaia
      belangeri).
AB  - We examined masseter and temporalis recruitment and firing patterns during
      chewing in five male Belanger's treeshrews (Tupaia belangeri), using
      electromyography (EMG). During chewing, the working-side masseters tend to show
      almost three times more scaled EMG activity than the balancing-side masseters.
      Similarly, the working-side temporalis muscles have more than twice the scaled
      EMG activity of the balancing-side temporalis. The relatively higher activity in
      the working-side muscles suggests that treeshrews recruit less force from their
      balancing-side muscles during chewing. Most of the jaw-closing muscles in
      treeshrews can be sorted into an early-firing or late-firing group, based on
      occurrence of peak activity during the chewing cycle. Specifically, the first
      group of jaw-closing muscles to reach peak activity consists of the working-side
      anterior and posterior temporalis and the balancing-side superficial masseter.
      The balancing-side anterior and posterior temporalis and the working-side
      superficial masseter peak later in the power stroke. The working-side deep
      masseter peaks, on average, slightly before the working-side superficial
      masseter. The balancing-side deep masseter typically peaks early, at about the
      same time as the balancing-side superficial masseter. Thus, treeshrews are unlike
      nonhuman anthropoids that peak their working-side deep masseters early and their
      balancing-side deep masseters late in the power stroke. Because in anthropoids
      the late firing of the balancing-side deep masseter contributes to wishboning of
      the symphysis, the treeshrew EMG data suggest that treeshrews do not routinely
      wishbone their symphyses during chewing. Based on the treeshrew EMG data, we
      speculate that during chewing, primitive euprimates 1) recruited more force from
      the working-side jaw-closing muscles as compared to the balancing-side muscles,
      2) fired an early group of jaw-closing muscles followed by a second group of
      muscles that peaked later in the power stroke, 3) did not fire their working-side
      deep masseter significantly earlier than their working-side superficial masseter,
      and 4) did not routinely fire their balancing-side deep masseter after the
      working-side superficial masseter.

PMID- 15486967
TI  - Characterization of chemisorbed hyaluronic acid directly immobilized on solid
      substrates.
AB  - Hyaluronic acid (HA) has a number of potential biomedical applications in drug
      delivery and tissue engineering. For these applications, a prerequisite is to
      understand the characteristic of HA films directly immobilized to solid
      substrates. Here, we demonstrate that high molecular weight HA can be directly
      immobilized onto hydrophilic substrates without any chemical manipulation,
      allowing for the formation of an ultrathin chemisorbed layer. Hyaluronic acid is
      stabilized on these surfaces through hydrogen bonding between the hydrophilic
      moieties in HA [such as carboxylic acid (-COOH) or hydroxyl (-OH) groups] with
      silanol (-SiOH), carboxylic acid or hydroxyl groups on the hydrophilic
      substrates. Despite the water solubility, the chemisorbed HA layer remained
      stable on glass or silicon oxide substrates for at least 7 days in phosphate
      buffered saline. Furthermore, HA immobilized on silicon and other dioxide
      surfaces in much higher quantities than other polysaccharides including dextran
      sulfate, heparin, heparin sulfate, chondroitin sulfate, dermatan sulfate, and
      alginic acid. This behavior is related to the molecular entanglement and
      intrinsic stiffness of HA as a result of strong internal and external hydrogen
      bonding as well as high molecular weight. These results demonstrate that HA can
      be used to coat surfaces through direct immobilization.

PMID- 15486966
TI  - Ferulic acid inhibits endothelial cell proliferation through NO down-regulating
      ERK1/2 pathway.
AB  - The aim of this study was to determine the antiproliferative mechanism of ferulic
      acid (FA) on serum induced ECV304 cell, a human umbilical vein endothelial line.
      The results suggest that FA significantly suppressed ECV304 cells proliferation
      and blocked the cell cycle in G0/G1 phase. Treatment of the cells with FA
      increased nitric oxide (NO) production and inactivated the extracellular signal
      regulated kinase (EERK1/2), and the NO donor, sodium nitroprusside, inhibited
      both ECV304 cells proliferation and phosphorylation of ERK1/2. However, the NO
      synthase inhibitor, Nomega-nitro-L-arginine methyl ester, caused ECV304 cells
      proliferation. PD 98059, the inhibitor of ERK1/2, had no effect on the NO
      production. These results indicate that NO suppressed ECV304 cells proliferation
      through down-regulating ERK1/2 pathway. Moreover, the inhibition of cell cycle
      progression was associated with the decrement of cyclin D1 expression and
      phosphorylation of retinoblastoma protein (pRb) by increment of p21 level. The
      findings not only present the first evidence that FA is a potent inhibitor on
      ECV304 cells proliferation, but also reveal the potential signaling molecules
      involved in its action.

PMID- 15486968
TI  - Regulation of the GATA3 promoter by human T-cell lymphotropic virus type I Tax
      protein.
AB  - The Human T-cell leukemia virus type I (HTLV-I) non-structural protein Tax plays
      a crucial role in cellular transformation. It activates the transcription factors
      of various cellular genes and interacts with cellular proteins. There is limited
      data available on the interaction between specific T-cell transcription factor
      GATA3 and Tax. Implications for the significance of GATA3 in T-cell development
      and function, T helper2 (Th2) differentiation, and a role of GATA3 during the
      immune response have been reported. To determine the effect of the Tax protein on
      GATA3 gene expression, we investigated the interaction between this protein and
      the GATA3 promoter and repressor regions. Results demonstrated an interaction
      between Tax and the GATA3 promoter via the transcription factor Sp1 and a role
      for Tax in the negative regulation of GATA3 expression, through its interaction
      with the repressor ZEB. This interaction may be involved in the pathophysiology
      of adult T-cell leukemia/lymphoma (ATL) and tropical spastic paraparesis/HTLV-I
      associated myelopathy (TSP/HAM).

PMID- 15486969
TI  - Mechanism of LIGHT/interferon-gamma-induced cell death in HT-29 cells.
AB  - LIGHT is a member of tumor necrosis factor (TNF) superfamily, and previous
      studies have indicated that in the presence of interferon-gamma (IFN-gamma),
      LIGHT through LTbetaR signaling can induce cell death with features unlike
      classic apoptosis. In present study, we investigated the mechanism of LIGHT/IFN
      gamma-induced cell death in HT-29 cells, where the cell death was profoundly
      induced when sub-toxic concentrations of LIGHT and IFN-gamma were co-treated.
      LIGHT/IFN-gamma-induced cell death was accompanied by DNA fragmentation and
      slight LDH release. This effect was not affected by caspase, JNK nor cathepsin B
      inhibitors, but was partially prevented by p38 mitogen-activated protein kinase
      (MAPK) and poly (ADP-ribose) polymerase (PARP) inhibitors, and abolished by
      aurintricarboxylic acid (ATA), which is an inhibitor of endonuclease and STATs
      signaling of IFN-gamma. Immunobloting reveals that LIGHT/IFN-gamma could induce
      p38 MAPK activity, Bak and Fas expression, but down-regulate Mcl-1. Besides,
      LIGHT/IFN-gamma could not activate caspase-3 and -9, but decreased mitochondrial
      membrane potential. Although LIGHT could not affect IFN-gamma-induced STAT1
      phosphorylation and transactivation activity, which was required for the
      sensitization of cell death, survival NF-kappaB signaling of LIGHT was inhibited
      by IFN-gamma. These data suggest that co-presence of LIGHT and IFN-gamma can
      induce an integrated interaction in signaling pathways, which lead to
      mitochondrial dysfunction and mix-type cell death, not involving caspase
      activation.

PMID- 15486970
TI  - Effects of low density lipoprotein receptor-related protein-1 on the expression
      of platelet-derived growth factor beta-receptor in vitro.
AB  - The low density lipoprotein receptor related protein-1 (LRP-1) is a cargo
      transport receptor that undergoes constitutive endocytosis and recycling.
      Platelet-derived growth factor-BB (PDGF-BB) binds to LRP-1 and may bridge LRP-1
      to PDGF receptors. Bridging of LRP-1 to other receptors by bifunctional ligands
      may represent a general mechanism whereby LRP-1 facilitates internalization of
      membrane proteins. The goal of this study was to determine whether LRP-1
      regulates cell-surface levels of PDGF beta-receptor or PDGF beta-receptor
      degradation following treatment with PDGF-BB. Unexpectedly, in both murine
      embryonic fibroblasts (MEFs) and HT 1080 fibrosarcoma cells, LRP-1 expression was
      associated with increased levels of PDGF beta-receptor. In MEFs, the mechanism
      involved increased PDGF beta-receptor transcription and/or RNA stabilization. LRP
      1 expression was not associated with increased levels of PDGF beta-receptor in
      Chinese hamster ovary (CHO) cells, suggesting that cell context is important. The
      kinetics of PDGF beta-receptor phosphorylation, in response to PDGF-BB, and the
      extent of degradation of PDGF beta-receptor were equivalent in LRP-1-expressing
      and -deficient MEFs. We conclude that PDGF beta-receptor expression and cell
      surface levels may be regulated by LRP-1; however, this activity is cell type
      specific. LRP-1 does not directly regulate PDGF beta-receptor phosphorylation or
      degradation in PDGF-BB-treated cells.

PMID- 15486971
TI  - Corneal epithelial cell growth over tethered-protein/peptide surface-modified
      hydrogels.
AB  - In this study, we investigated the corneal epithelial cell growth rate and
      adhesion to novel hydrogels with (1) extracellular matrix proteins [fibronectin,
      laminin, substance P, and insulin-like growth factor-1 (IGF-1)] and (2) peptide
      sequences [RGD and fibronectin adhesion-promoting peptide (FAP)] tethered to
      their surface on poly(ethylene glycol) (PEG) chains. The growth rate to
      confluence of primary rabbit cornea epithelial cells was compared for plain
      polymethacrylic acid-co-hydroxyethyl methacrylate (PHEMA/MAA) hydrogels,
      PHEMA/MAA hydrogels coated with extracellular matrix proteins or peptides, and
      PHEMA/MAA hydrogels with tethered extracellular matrix proteins or peptides on
      the surface. The development of focal adhesions by the epithelial cells grown on
      the surfaces was determined by F-actin staining. Little to no epithelial cell
      growth occurred on the plain hydrogel surfaces throughout the 15-day culture
      period. Of the coated hydrogels, only the fibronectin-coated surfaces showed a
      significant increase in cell growth compared to plain hydrogels (p < 0.009).
      However, even these surfaces reached a maximum of only 20% confluence. Laminin,
      fibronectin adhesion-promoting peptide (FAP), and fibronectin/laminin (1:1)
      tether-modified hydrogels all achieved 100% confluence by the end of the culture
      period, although the rates at which confluence was reached differed. F-actin
      staining showed that focal adhesions were formed for the laminin, FAP, and
      fibronectin/laminin tether-modified surfaces. The results support the hypothesis
      that tethering certain extracellular matrix proteins and/or peptides to the
      hydrogel surface enhances epithelial cell growth and adhesion, compared with that
      seen for protein-coated or plain hydrogel surfaces.

PMID- 15486972
TI  - Aluminum decreases the glutathione regeneration by the inhibition of NADP
      isocitrate dehydrogenase in mitochondria.
AB  - Effect of aluminum on the NADPH supply and glutathione regeneration in
      mitochondria was analyzed. Reduced glutathione acted as a principal scavenger of
      reactive oxygen species in mitochondria. Aluminum inhibited the regeneration of
      glutathione from the oxidized form, and the effect was due to the inhibition of
      NADP-isocitrate dehydrogenase the only enzyme supplying NADPH in mitochondria. In
      cytosol, aluminum inhibited the glutathione regeneration dependent on NADPH
      supply by malic enzyme and NADP-isocitrate dehydrogenase, but did not affect the
      glucose 6-phosphate dehydrogenase dependent glutathione formation. Aluminum can
      cause oxidative damage on cellular biological processes by inhibiting glutathione
      regeneration through the inhibition of NADPH supply in mitochondria, but only a
      little inhibitory effect on the glutathione generation in cytosol.

PMID- 15486973
TI  - Poly(ADP-ribose) polymerase-1: association with nuclear lamins in rodent liver
      cells.
AB  - The distribution of poly(ADP-ribose) polymerase-1 (PARP-1) over different nuclear
      compartments was studied by nuclear fractionation procedures and Western analysis
      revealing a prominent role of the nuclear matrix. This structure is operationally
      defined by the solubility properties of the A- and B-type lamins under defined
      experimental conditions. We consistently observed that most of the nuclear matrix
      associated PARP-1 partitioned, in an active form, with the insoluble, lamin
      enriched protein fractions that were prepared by a variety of established
      biochemical procedures. These PARP-1-protein interactions resisted salt
      extraction, disulfide reduction, RNase and DNase digestion. An inherent ability
      of PARP-1 to reassemble with the lamins became evident after a cycle of
      solubilization/dialysis using either urea or Triton X-100 and disulfide
      reduction, indicating that these interactions were dominated by hydrophobic
      forces. Together with in vivo crosslinking and co-immunoprecipitation experiments
      our results show that the lamins are prominent PARP-1-binding partners which
      could contribute to the functional sequestration of the enzyme on the nuclear
      matrix.

PMID- 15486974
TI  - Carboxy-terminal fragment of osteogenic growth peptide regulates myeloid
      differentiation through RhoA.
AB  - The carboxy-terminal fragment of osteogenic growth peptide, OGP(10-14), is a
      pentapeptide with bone anabolic effects and hematopoietic activity. The latter
      activity appears to be largely enhanced by specific growth factors. To study the
      direct activity of OGP(10-14) on myeloid cells, we tested the pentapeptide
      proliferating/differentiating effects in HL60 cell line. In this cell line,
      OGP(10-14) significantly inhibited cell proliferation, and enhanced
      myeloperoxidase (MPO) activity and nitroblue tetrazolium reducing ability.
      Moreover, it induced cytoskeleton remodeling and small GTP-binding protein RhoA
      activation. RhoA, which is known to be involved in HL60 differentiation, mediated
      these effects as shown by using its specific inhibitor, C3. Treatment with GM-CSF
      had a comparable OGP(10-14) activity on proliferation, MPO expression, and RhoA
      activation. Further studies on cell proliferation and RhoA activation proved
      enhanced activity by association of the two factors. These results strongly
      suggest that OGP(10-14) acts directly on HL60 cells by activating RhoA signaling
      although other possibilities cannot be ruled out.

PMID- 15486975
TI  - Cooperative activation of atrial naturetic peptide promoter by dHAND and MEF2C.
AB  - An intricate array of cell-specific multiprotein complexes participate in
      programs of cell-specific gene expression through combinatorial interaction with
      different transcription factors and cofactors. The dHAND basic helix-loop-helix
      (bHLH) transcription factor, which is essential for heart development and extra
      embryonic structures, is thought to regulate cardiomyocyte-specific gene
      expression through combinatorial interactions with other cardiac-restricted
      transcription factors such as GATA4 and NKX2.5. Here, we determine that dHAND
      also interacts with the myocyte enhancer binding factor-2c (MEF2C) protein, which
      belongs to MADS-box transcription factors and is essential for heart development.
      dHAND and MEF2C synergistically activated expression of the atrial naturetic
      peptide gene (ANP) in transfected HeLa cells. GST-pulldown and
      immunoprecipitation assay demonstrate that full-length MEF2C protein is able to
      interact with dHAND in vitro and in vivo, just like MEF2A and bHLH transcription
      factors MyoD in skeletal muscle cells. In addition, electrophoretic mobility
      shift assays (EMSAs) demonstrate that MEF2C and dHAND do not influence each
      other's DNA binding activity. Using chromatin immunoprecipitation (ChIP) analysis
      in H9c2 cells we show that dHAND interact with MEF2C to form protein complex and
      bind A/T sequence in promoter of ANP. Taken together with previous observations,
      these results suggest the existence of large multiprotein transcriptional complex
      with core DNA binding proteins that physically interact with other
      transcriptional factors to form favorable conformation to potentiate
      transcription.

PMID- 15486977
TI  - Praise ye the god of iron.

PMID- 15486979
TI  - Hepatolymphomania.

PMID- 15486980
TI  - Can Turner syndrome teach us about the pathogenesis of chronic cholestasis?

PMID- 15486981
TI  - Immune system homeostasis during acute hepatitis C: viral escape or T-cell
      regulation?

PMID- 15486982
TI  - To be or not to be NKT: natural killer T cells in the liver.
AB  - Much of the hepatology literature to date has focused on the adaptive, antigen
      specific response mediated by classical T-cell populations in both the protection
      and pathogenesis of liver disease. However, the liver is selectively enriched for
      cells representative of innate immunity, including natural killer T (NKT) cells.
      In particular, certain CD1d-reactive T cells are present at much higher
      frequencies in the liver than in the peripheral blood. Although these cells have
      previously been defined mostly on the basis of phenotypic markers, recent
      emerging literature regarding NKT cell populations has revealed considerable
      functional complexity. This review summarizes the recent literature regarding NKT
      cells, which may have important roles in a variety of liver diseases. Although
      there is an abundance of literature on the phenotype, distribution, and function
      of these cells in mice, much less is known about them in human health or liver
      diseases.

PMID- 15486983
TI  - ApcMin/+ mouse model of colon cancer: gene expression profiling in tumors.
AB  - The Apc(Min/+) mouse is a popular animal model for studies of human colon cancer,
      but the molecular changes associated with neoplasia in this system have only been
      partially characterized. Our aim was to identify novel genes involved in
      tumorigenesis in this model. RNA from intestinal adenomas and from pre-neoplastic
      small intestine were prepared from six Apc(Min/+) mice. The tumor transcriptomes
      were analyzed with high-density oligonucleotide microarrays representing
      approximately 12,000 probe sets; we compared their profiles with those of matched
      pre-neoplastic intestine. Stringent analysis revealed reproducible changes for 98
      probe sets representing 90 genes, including novel observations regarding 50 genes
      whose involvement in this mouse model has never been reported. In addition to the
      expected changes in growth regulatory genes, the altered gene products could be
      assigned to four functional groupings that should enhance tumorigenesis:
      metabolic changes that would result in a high rate of glycolysis, alterations in
      enzymes involved in reactive oxygen species or carcinogen metabolism,
      cytoskeletal elements, and proteins involved in tumor invasion or angiogenesis. A
      fifth group consisted of expression changes that might restrict tumor
      progression, suggesting that the adenomatous state reflects a balance of pro- and
      anti-tumorigenic factors. Since many of the altered genes had not previously been
      reported to be involved in any tumorigenic processes, our observations provide a
      host of new candidates for potential modulation to prevent or treat intestinal
      neoplasia.

PMID- 15486985
TI  - Regulation of expression of the early growth response gene-1 (EGR-1) in malignant
      and benign cells of the prostate.
AB  - BACKGROUND: Expression of the early growth response gene-1 (EGR-1) is elevated in
      prostate cancer and correlates with tumor progression. This study provides
      insight into the mechanism(s) that regulate EGR-1 expression and activity in
      malignant and benign prostate cells. METHODS: Western blotting and in vitro pulse
      labeling were used to examine EGR-1 protein levels and half-life in malignant (PC
      3) and benign (BPH-1) prostate cell lines. EGR-1 functional ability was assessed
      by transient transfections with an EGR-1 promoter driven luciferase plasmid and
      electromobility shift assays (EMSAs) to assess DNA binding of the EGR-1 protein.
      Protein levels of casein kinase II (CKII) were evaluated by Western blotting.
      RESULTS: PC-3 cells maintain high steady-state levels of EGR-1 protein, in part
      due to a longer half-life of EGR-1 protein. BPH-1 cells responded to mitogenic
      stimuli with increased EGR-1 protein levels, and enhanced transcriptional
      activity. In contrast, PC-3 cells showed no response to stimuli. DNA binding of
      EGR-1 was higher in BPH-1 cells than in PC-3 cells. This appears to be related to
      the heavily phosphorylated state of EGR-1 in PC-3 cells which is correlated with
      increased levels of CKII found in these cells. CONCLUSIONS: PC-3 cells maintain a
      long lasting, heavily phosphorylated pool of EGR-1, which binds poorly to DNA and
      responds poorly to mitogenic stimulus. BPH-1 cells, in contrast, maintain a more
      responsive, less phosphorylated EGR-1 pool. These findings suggest that EGR-1
      expression and activity is differentially regulated in PC-3 and BPH-1 cell lines.

PMID- 15486986
TI  - Comparison of continuous overt speech fMRI using BOLD and arterial spin labeling.
AB  - Overt speech production in functional magnetic resonance imaging (fMRI) studies
      is often associated with imaging artifacts, attributable to both movement and
      susceptibility. Various image-processing methods have been proposed to remove
      these artifacts from the data but none of these methods has been shown to work
      with continuous overt speech, at least over periods greater than 3 s. In this
      study natural, continuous, overt sentence production was evaluated in normal
      volunteers using both arterial spin labeling (ASL) and conventional echoplanar
      blood oxygenation level-dependent (BOLD) imaging sequences on the same 1.5-T
      scanner. We found a high congruency between activation results obtained with ASL
      and the de facto gold standard in overt language production imaging, positron
      emission tomography (PET). No task-related artifacts were found in the ASL study.
      However, the BOLD data showed artifacts that appeared as large bilateral false
      positive temporopolar activations; percent signal change estimated in these
      regions showed signal increases and temporal dynamics that were incongruent with
      typical BOLD activations. These artifacts were not distributed uniformly, but
      were aligned at the frontotemporal base, close to the oropharynx. The calculated
      head movement parameters for overt speech blocks were within the range of the
      rest blocks, indicating that head movement is unlikely the reason for the
      artifact. We conclude that ASL is not influenced by overt speech artifacts,
      whereas BOLD showed significant susceptibility artifacts, especially in the
      opercular and insular regions, where activation would be expected. ASL may prove
      to be the method of choice for fMRI investigations of continuous overt speech.

PMID- 15486987
TI  - Genome-wide characterization of gene expression variations and DNA copy number
      changes in prostate cancer cell lines.
AB  - BACKGROUND: The aim of this study was to characterize gene expression and DNA
      copy number profiles in androgen sensitive (AS) and androgen insensitive (AI)
      prostate cancer cell lines on a genome-wide scale. METHODS: Gene expression
      profiles and DNA copy number changes were examined using DNA microarrays in eight
      commonly used prostate cancer cell lines. Chromosomal regions with DNA copy
      number changes were identified using cluster along chromosome (CLAC). RESULTS:
      There were discrete differences in gene expression patterns between AS and AI
      cells that were not limited to androgen-responsive genes. AI cells displayed more
      DNA copy number changes, especially amplifications, than AS cells. The gene
      expression profiles of cell lines showed limited similarities to prostate tumors
      harvested at surgery. CONCLUSIONS: AS and AI cell lines are different in their
      transcriptional programs and degree of DNA copy number alterations. This dataset
      provides a context for the use of prostate cancer cell lines as models for
      clinical cancers.

PMID- 15486988
TI  - Crossed cerebro-cerebellar language dominance.
AB  - In addition to its traditional role in motor control, the cerebellum has been
      implicated in various cognitive and linguistic functions. Lesion, anatomic, and
      functional imaging studies indicate a link between left frontal language regions
      and the right cerebellum. To probe the specificity of this circuit, we examined
      the association between language-related lateralized activation of the frontal
      cortex with lateralized activation of the cerebellum. Functional magnetic
      resonance imaging (fMRI) was carried out during letter-cued word generation in 14
      healthy subjects: 7 subjects displayed typical left-hemisphere and 7 subjects
      displayed atypical right-hemisphere language dominance. We found activation of
      the cerebellar hemisphere contralateral to the language-dominant cerebral
      hemisphere in each subject. The cerebellar activation was confined to the lateral
      posterior cerebellar hemisphere (lobule VI, VII B, Cr I, Cr II). This study
      demonstrates that crossed cerebral and cerebellar language dominance is a typical
      characteristic of brain organization. The functional significance of the reported
      activations can now be tested in patients with lesions of the lateral posterior
      cerebellum.

PMID- 15486989
TI  - Aging-associated changes in gene expression in the ACI rat prostate: Implications
      for carcinogenesis.
AB  - BACKGROUND: Prostate cancer is the most frequently diagnosed neoplasm and the
      second leading cause of cancer-related mortality in men. Although the incidence
      of prostate cancer increases with age, the link between aging and prostate cancer
      is poorly understood. METHODS: Affymetrix oligonucleotide microarrays were used
      to analyze the mRNA expression levels in the dorsolateral prostates from 6- and
      18-month-old ACI rats. Real-time RT-PCR and immunohistochemistry was performed to
      validate microarray data in a select set of genes. RESULTS: Microarray analysis
      revealed changes in gene expression associated with inflammation, oxidative
      stress, tissue remodeling, and energy metabolism. Most of these changes have been
      related to increased proliferative status of the prostate, anti-apoptosis,
      activated stroma, and alteration of the energy metabolism. CONCLUSIONS: Age
      associated alterations in the gene expression profile may put the aging prostate
      in risk for the initiation, promotion, and progression of neoplastic
      transformation in both our animal model and humans.

PMID- 15486990
TI  - Regional cerebral blood flow in children with attention deficit hyperactivity
      disorder: comparison before and after methylphenidate treatment.
AB  - Differences in brain activity of children with attention deficit hyperactivity
      disorder (ADHD) have been compared to normal healthy controls, suggesting neural
      correlates of cognitive/behavioral symptoms. Symptoms are improved with
      methylphenidate treatment but limited sources can be cited to show how brain
      activity in ADHD is altered after pharmacologic treatment. We investigated how
      long-term oral medication of methylphenidate affects the resting regional
      cerebral blood flow (rCBF) in ADHD children, using single photon emission
      computerized tomography (SPECT). rCBF was decreased in the orbitofrontal cortex
      and middle temporal gyrus in the right hemisphere whereas it was increased in the
      dorsomedial prefrontal and somatosensory area bilaterally in drug-naive ADHD
      children compared to control child subjects. After treatment with
      methylphenidate, the extent of hyperperfusion in the somatosensory area was
      reduced and significant reduction of rCBF was found in the right striatum for the
      first time. Methylphenidate treatment also resulted in rCBF increase in superior
      prefrontal and reduction in ventral higher visual areas bilaterally. The results
      indicated that improving ADHD symptom after methylphenidate is associated with
      normalization of abnormally reduced orbitofrontal activity and abnormally
      increased somatosensory cortical activity. These changes were accompanied with
      reduced striatum activity lower than that of normal controls. These changes might
      be associated with improving ADHD to control attention and motor response to
      irrelevant environmental stimuli after methylphenidate treatment.

PMID- 15486991
TI  - Induction of AP-1 activity by androgen activation of the androgen receptor in
      LNCaP human prostate carcinoma cells.
AB  - BACKGROUND: The androgen receptor and activator protein-1 (AP-1) transcription
      factors affect growth regulation in normal and cancerous prostate cells. Effects
      of androgen-activated androgen receptor on AP-1 activity were determined in the
      LNCaP human prostate carcinoma cell model. METHODS: Cells were exposed to 1 nM
      androgen +/- antiandrogen bicalutamide. Cellular growth and cell cycle effects
      were determined by DNA, viability, and bromodeoxyuridine (BrdU) fluorescence
      activated cell sorter (FACS) assays. AP-1 effects were determined by an AP-1
      luciferase enzyme reporter vector for transcriptional activity, electrophoretic
      mobility shift assay (EMSA)/antibody supershift for DNA-binding, quantitative RT
      PCR for mRNA, and immunoblot for protein. RESULTS: Androgen induced G(1) growth
      arrest. This growth arrest was abrogated by treatment with bicalutamide,
      demonstrating that growth arrest by androgen was due to androgen receptor
      activation. Concurrently, AP-1 DNA-binding and transcriptional activity was
      induced over 96 hr androgen exposure, which was also inhibited by bicalutamide.
      Interestingly, although no change in AP-1 transcriptional activity was observed
      24 hr after androgen exposure, there was an increase in Fra-2 expression and AP-1
      DNA-binding. Paradoxically, while Fra-2 mRNA and protein levels continued to
      increase, binding of Fra-2 to the AP-1 site decreased over 96 hr, with a
      concomitant increase in JunD AP-1-binding and a marked increase in expression of
      the 35 kDa form of JunD. Enhanced expression of this short form of JunD is a
      novel effect of androgen exposure that occurred during the 24-96 hr time period,
      as growth effects emerged. CONCLUSION: Activation of androgen receptor by
      androgen induces changes in AP-1 activity and AP-1 factor DNA-binding that may
      contribute significantly to androgen-induced changes in prostate cancer cell
      growth.

PMID- 15486992
TI  - The assessment of depression inventory (ADI): a new instrument used to measure
      depression and to detect honesty of response.
AB  - We examined the psychometric properties of the Assessment of Depression Inventory
      (ADI). This instrument assesses depression and also has validity scales that
      address response honesty. Three studies were conducted. The first describes the
      development of the ADI. The second compared the concurrent validity of the ADI
      Depression (Dep) scale with the BDI-II, and the ADI Feigning (Fg) scale responses
      of psychiatric inpatients with those of a sample of community volunteers asked to
      feign depression. The third study was used to cross-validate the results with a
      separate sample of participants. The ADI Dep scale correlated highly with the BDI
      II. Significant differences were also found between the honest patient responders
      and the non-patient feigners on the Fg scale. The data supports the ADI validity
      scales as measures of response style and the Dep scale as a measure of
      depression.

PMID- 15486994
TI  - Androgen receptor corepressors: an overview.
AB  - Androgens play pivotal roles in sex differentiation and development, in
      reproductive functions, and sexual behavior. The actions of androgens are
      mediated through the intracellular androgen receptor (AR), a member of the
      nuclear receptor (NR) superfamily, which regulates a wide range of target gene
      expression. Recent studies indicate that the proper transcriptional activity of
      AR is modulated by AR coregulators, including coactivators that can enhance AR
      transactivation and corepressors that can suppress AR transactivation. Here, we
      summarize the recent discoveries relating to AR corepressor function with the
      following different mechanisms: (1) corepressors that inhibit the DNA binding or
      nuclear translocation of AR; (2) corepressors that recruit histone deacetylases;
      (3) corepressors that interrupt the interaction between AR and its coactivators;
      (4) corepressors that interrupt the interaction between the N-terminus and C
      terminus of AR; (5) corepressors that function as scaffolds for other AR
      coregulators; (6) corepressors that target the basal transcriptional machinery;
      (7) other mechanisms. The potential impact and future directions of AR
      corepressors are also discussed.

PMID- 15486993
TI  - C/EBPdelta is a downstream mediator of IL-6 induced growth inhibition of prostate
      cancer cells.
AB  - BACKGROUND: Although a number of reports have investigated the effects of IL-6
      family cytokines on prostate cell growth, there is limited information available
      identifying IL-6 inducible downstream effector genes and their function in growth
      control. Previous studies have demonstrated that IL-6 treatment results in the
      activation of signal transducer and activator of transcription3 (STAT3) in
      prostate cancer cells. The goal of this study was to investigate the influence of
      IL-6 treatment and activation of the Jak/STAT signal transduction pathway on
      C/EBPdelta gene expression and growth inhibition of human prostate cancer cells.
      METHODS: Expression of C/EBPdelta and STAT3 activation were assayed using
      Northern and Western blotting techniques. Proliferation was assessed by [(3)H]
      thymidine incorporation, flow cytometry, and colony formation analyses. The
      analysis of the transcriptional regulation of C/EBPdelta was performed using
      luciferase-reporter constructs. RESULTS: In this report, we demonstrate that IL-6
      treatment induces STAT3 activation (pSTAT3), pSTAT3 binds to the human C/EBPdelta
      gene promoter and induces its expression. We also demonstrate that C/EBPdelta
      over-expression is capable of suppressing prostate cancer cell growth.
      CONCLUSIONS: These results demonstrate that C/EBPdelta gene expression is
      increased in IL-6 treated LNCaP cells. Increased C/EBPdelta gene expression plays
      an important role in IL-6/STAT3 mediated growth arrest of LNCaP prostate cancer
      cells. Ongoing studies are investigating the mechanism by which C/EBPdelta
      controls prostate cancer cell growth and the potential role of C/EBPdelta in the
      survival and chemo resistance of prostate cancer metastasis. (c) 2004 Wiley-Liss,
      Inc.

PMID- 15486995
TI  - Apigenin drives the production of reactive oxygen species and initiates a
      mitochondrial mediated cell death pathway in prostate epithelial cells.
AB  - BACKGROUND: Phytoestrogens may reduce tumorigenesis in prostate cancer. We
      screened five phytoestrogens for their effect on cell growth and apoptosis in PWR
      1E, LNCaP, PC-3, and DU145 prostate epithelial cells in vitro. METHODS: We
      assessed cell number, proliferation, and apoptosis using crystal violet assays,
      flow cytometric analysis, and TUNEL. Focusing specifically on apigenin we
      assessed the ability of calpain, serine protease, caspase, estrogen receptor, and
      ceramide synthase inhibitors to block apigenin induced apoptosis. We also
      analyzed caspase 3, 7, 8, 9, Bcl-2, Bax, Bid, and cytochrome C by Western
      analysis, and mitochondrial permeability and reactive oxygen species production
      by flow cytometry using mitosensor(TM) and DCFH-DA, respectively. RESULTS:
      Apigenin and silybinin significantly reduced cell number, with apigenin inducing
      apoptosis in PWR-1E, LNCaP, PC-3, and DU145 cells. The PC-3 and DU145 cells were
      less susceptible to apigenin induced apoptosis then LNCaP and PWR-1E cells. The
      induction of apoptosis by apigenin was caspase dependent. Apigenin generated
      reactive oxygen species, a loss of mitochondrial Bcl-2 expression, mitochondrial
      permeability, cytochrome C release, and the cleavage of caspase 3, 7, 8, and 9
      and the concomitant cleavage of the inhibitor of apoptosis protein, cIAP-2. The
      overexpression of Bcl-2 in LNCaP B10 cells reduced the apoptotic effects of
      apigenin. CONCLUSIONS: Apigenin induces cell death in prostate epithelial cells
      using a mitochondrial mediated cell death pathway. Bcl-2 has a role in inhibiting
      apigenin induced cell death in prostate epithelial cells.

PMID- 15486996
TI  - Motor training as treatment in focal hand dystonia.
AB  - Focal hand dystonia may arise as a result of aberrant plasticity from excessive
      repetitive use. Improvement might be possible with appropriate motor training.
      Focusing on trying to decrease abnormal overflow of movement to fingers not
      involved in a task, we developed a motor training program for individualized
      finger movements. Ten patients with writer's cramp participated in the motor
      training program. Evaluation was done with the Fahn dystonia scale, kinematic
      analysis of handwriting, transcranial magnetic stimulation (TMS), and
      electroencephalography (EEG). Clinical improvement of dystonia was significant
      using the Fahn dystonia scale, and 6 patients reported an improvement in writing.
      The handwriting analysis showed a trend for improvement after training in simple
      exercises. There were no changes in cortical excitability measured by TMS and
      EEG. Whereas this method of motor training for 4 weeks led to mild subjective
      improvement and some improvement in handwriting, it is not sufficient to reverse
      motor cortex abnormalities measured by TMS and EEG.

PMID- 15486997
TI  - Sacsin-related autosomal recessive ataxia without prominent retinal myelinated
      fibers in Japan.
AB  - Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) has been
      described in the Quebec region and in Tunisia. We report on two Japanese siblings
      with a new homozygous mutation (6543 del A) of the SACS gene. Compared with
      previously reported ARSACS patients, both of these patients had a unique
      phenotype characterized by dementia, ophthalmoplegia, and the absence of
      prominent retinal myelinated fibers.

PMID- 15486998
TI  - Ontogeny of tracheal system structure: a light and electron-microscopy study of
      the metathoracic femur of the American locust, Schistocerca americana.
AB  - Does oxygen delivery become more challenging for insects as they increase in
      size? To partially test this hypothesis, we used quantitative light and electron
      microscopy to estimate the oxygen delivery capacity for two steps of tracheal
      oxygen delivery within the metathoracic femur (jumping leg) for 2nd instar (about
      47 mg) and adult (about 1.7 g) locusts, Schistocerca americana. The fractional
      cross-sectional areas of the major tracheae running longitudinally along the leg
      were similar in adults and 2nd instars; however, since the legs of adults are
      longer, the mass-specific diffusive conductances of these tracheae were 4-fold
      greater in 2nd instars. Diffusive gas exchange longitudinally along the leg is
      easily possible for 2nd instars but not adults, who have many air sacs within the
      femur. Mitochondrial content fell proximally to distally within the femur in 2nd
      instars but not adults, supporting the hypothesis that diffusion was more
      important for the former. Lateral diffusing capacities of the tracheal walls were
      12-fold greater in adults than 2nd instars. This was primarily due to differences
      in the smallest tracheal class (tracheoles), which had thinner epidermal and
      cuticular layers, greater surface to volume ratios, and greater mass-specific
      surface areas in adults. Adults also had greater mitochondrial contents, larger
      cell sizes and more intracellular tracheae. Thus, larger insects do not
      necessarily face greater problems with oxygen delivery; adult grasshoppers have
      superior oxygen delivery systems and greater mass-specific aerobic capacities in
      their legs than smaller/younger insects.

PMID- 15486999
TI  - Five-year follow-up study of hyperechogenicity of the substantia nigra in
      Parkinson's disease.
AB  - Using transcranial sonography, an area of hyperechogenicity at the substantia
      nigra (SN) may be detected as a typical marker in patients with Parkinson's
      disease (PD) as well as in approximately 9% of healthy subjects vulnerable to
      nigrostriatal impairment. In this longitudinal study, we provide evidence that
      the area of SN hyperechogenicity does not change in the course of PD. In
      conjunction with earlier findings in children and adolescents, this evidence
      indicates that, from late adolescence onward, this ultrasound finding is a trait
      marker for nigrostriatal vulnerability.

PMID- 15487000
TI  - Embryological aspects of inducible morphological defenses in Daphnia.
AB  - Many cases of predator-induced morphological plasticity in daphnids are well
      studied examples of inducible defenses. However, little is known about the early
      development of these sometimes conspicuous traits. We compared for the first time
      in five different Daphnia species the embryonic development of predator-induced
      and noninduced animals using scanning electron microscopy (SEM). We observed
      significant morphological changes in the last embryonic stage in helmet formation
      in Daphnia cucullata and in neck-pedestal development in Daphnia pulex. In
      contrast, no morphological changes could be found during embryogenesis between
      induced and noninduced Daphnia lumholtzi, D. longicephala, and D. ambigua.
      Strategies for initiating the defensive traits differ among Daphnia species
      because of trade-offs between environmental requirements and developmental
      constraints. Some general features of Daphnia embryonic development are described
      using SEM. All Daphnia embryos have to shed at least three different membranes
      before leaving the brood pouch of the mother. After the embryos shed the third
      membrane, chemosensillae that are likely able to detect predator-released
      chemicals are exposed to the olfactory environment.

PMID- 15487001
TI  - Development of the genital ducts in Telmatodrilinae (Tubificidae, Clitellata).
AB  - In Tubificidae, the male genital duct comprises a funnel in the testes segment,
      followed by a vas deferens, an atrium, and, frequently, a copulatory structure in
      the adjacent ovarian segment. There may also be a diffuse or compact prostate
      gland in association with the duct. The morphology and position of the genital
      ducts are important for the classification of the oligochaetous Clitellata.
      Different parts of the male duct, however, have been named without regard to
      whether they are homologous or not. One way to establish better hypotheses of
      homology is to study the detailed morphology and/or the development of the
      genital ducts. The morphogenesis of the genital ducts in Alexandrovia onegensis
      (Telmatodrilinae) is described. The male funnel originates by multiplication of
      peritoneal (mesodermal) cells in the posterior septum in the testes segment. A
      cord of these cells breaks through the septum and grows backwards into the next
      segment, where it connects to the epidermis. This cord gives rise to the vas
      deferens, and is therefore mesodermal in origin. The atrium in A. onegensis
      develops from a primary epidermal (ectodermal) invagination. The vas deferens and
      atrium connect and a continuous duct from the testes segment to the exterior is
      formed. Several compact prostate glands develop along the atrium, each being
      formed from cells in the atrial epithelium. The spermatheca develops from an
      invagination of the epidermis in the testes segment. The female duct is formed
      from peritoneal (mesodermal) cells in the posterior septum in the ovarian
      segment. These developmental findings strengthen the hypothesis about a closer
      relationship between the Telmatodrilinae and Tubificinae (both Tubificidae).

PMID- 15487002
TI  - Avian fissura prima: differential accumulation of extracellular matrix at a fold.
AB  - Extracellular matrix components that flank the fissura prima, a primary surface
      infolding of the cerebellum in birds and mammals, were examined in the embryonic
      chick using light and transmission electron microscopy. Cerebella dissected from
      Day 10 embryos were perfused with a paraformaldehyde-glutaraldehyde-tannic acid
      primary fixative and sectioned in the sagittal plane through the mid-vermis.
      Ultrastructural analysis revealed a distinct, continuous basal lamina separating
      the organ parenchyma (epithelia) from pia mater (mesenchyme) at the fissure
      surface (arbitrarily labeled; fissure floor, folia wall, and folia apex). The
      basal lamina was significantly thicker (P < 0.001) at the fissure floor compared
      to that found at the folia wall, which was significantly thicker (P < 0.001) than
      that observed at the folia apex. Folds in the basal lamina were observed
      exclusively at the fissure floor. Surface-associated collagen fibrils were
      distributed in an aligned, relatively dense manner at the fissure floor, compared
      with fibrils observed in various orientations and widely separated or absent at
      the folia wall and folia apex. Metachromasia was more pronounced in the fissure
      floor than in either the folia wall or folia apex in methylene blue-stained
      tissue sections. Together, the thicker, folded basal lamina and densely aligned
      collagen fibrils at the fissure floor provide a chemical rationale for this color
      change. These findings suggest that the differential accumulation of
      extracellular matrix at the fissura prima is positioned to play a structural
      and/or biochemical role in the maintenance of this fold.

PMID- 15487003
TI  - Release of aldosterone and catecholamines from the interrenal gland of Triturus
      carnifex in response to adrenocorticotropic hormone (ACTH) administration.
AB  - The influence of adrenocorticotropic hormone (ACTH) on the interrenal gland of
      Triturus carnifex was investigated by in vivo administration of synthetic ACTH.
      The effects were evaluated by examination of the ultrastructural morphological
      and morphometrical features of the tissues as well as the circulating serum
      levels of aldosterone, noradrenaline (NA), and adrenaline (A). In June and
      November, ACTH administration increased aldosterone release (from 281.50 +/- 1.60
      pg/ml in carrier-injected newts to 597.02 +/- 3.35 pg/ml in June; from 187.45 +/-
      1.34 pg/ml in carrier-injected animals to 651.00 +/- 3.61 pg/ml in November). The
      steroidogenic cells showed clear signs of stimulation, together with a reduction
      of lipid content in June and an increase of lipid content in November. Moreover,
      ACTH administration decreased the mean total number of secretory vesicles in the
      chromaffin cells in June (from 7.73 +/- 0.60 granules/microm2 in carrier-injected
      animals to 5.91 +/- 0.40 granules/microm2) and November (from 7.78 +/- 0.75
      granules/microm2 in carrier-injected newts to 4.87 +/- 0.40 granules/microm2). In
      June, however, when T. carnifex chromaffin cells contain almost exclusively NA
      granules (NA: 7.42 +/- 0.86 granules/microm2; A: 0.32 +/- 0.13 granules/microm2),
      ACTH decreased NA content (5.52 +/- 0.32 granules/microm2) increasing NA release
      (from 639.82 +/- 3.30 pg/ml in carrier-injected to 880.55 +/- 4.52 pg/ml). In
      November, when both catecholamines, NA (3.92 +/- 0.34 granules/microm2) and A
      (3.84 +/- 0.33 granules/microm2), are present in the chromaffin cells, ACTH
      administration reduced A content (1.02 +/- 0.20 granules/microm2), enhancing
      adrenaline secretion (from 681.30 +/- 3.62 pg/ml in carrier-injected newts to
      1,335.73 +/- 9.03 pg/ml). The results of this study indicate that ACTH influences
      the steroidogenic tissue, eliciting aldosterone release. The effects on the
      chromaffin tissue, increase of NA or A secretion, according to the period of
      chromaffin cell functional cycle, may be direct and/or mediated through the
      increase of aldosterone release. Finally, the lack of an increase of A content in
      the chromaffin cells, or A serum level, following ACTH administration in June
      might suggest an independence of PNMT enzyme on corticosteroids.

PMID- 15487004
TI  - Secretory and basal cells of the epithelium of the tubular glands in the male
      Mullerian gland of the caecilian Uraeotyphlus narayani (Amphibia: Gymnophiona).
AB  - Caecilians are exceptional among the vertebrates in that males retain the
      Mullerian duct as a functional glandular structure. The Mullerian gland on each
      side is formed from a large number of tubular glands connecting to a central
      duct, which either connects to the urogenital duct or opens directly into the
      cloaca. The Mullerian gland is believed to secrete a substance to be added to the
      sperm during ejaculation. Thus, the Mullerian gland could function as a male
      accessory reproductive gland. Recently, we described the male Mullerian gland of
      Uraeotyphlus narayani using light and transmission electron microscopy (TEM) and
      histochemistry. The present TEM study reports that the secretory cells of both
      the tubular and basal portions of the tubular glands of the male Mullerian gland
      of this caecilian produce secretion granules in the same manner as do other
      glandular epithelial cells. The secretion granules are released in the form of
      structured granules into the lumen of the tubular glands, and such granules are
      traceable to the lumen of the central duct of the Mullerian gland. This is
      comparable to the situation prevailing in the epididymal epithelium of several
      reptiles. In the secretory cells of the basal portion of the tubular glands,
      mitochondria are intimately associated with fabrication of the secretion
      granules. The structural and functional organization of the epithelium of the
      basal portion of the tubular glands is complicated by the presence of basal
      cells. This study suggests the origin of the basal cells from peritubular tissue
      leukocytes. The study also indicates a role for the basal cells in acquiring
      secretion granules from the neighboring secretory cells and processing them into
      lipofuscin material in the context of regression of the Mullerian gland during
      the period of reproductive quiescence. In these respects the basal cells match
      those in the epithelial lining of the epididymis of amniotes.

PMID- 15487005
TI  - Functional morphology of the ear in fossorial rodents, Microtus arvalis and
      Arvicola terrestris.
AB  - Functionally relevant features and parameters of the outer, middle, and inner ear
      were studied morphologically and morphometrically in two species of voles,
      smaller Microtus arvalis and larger Arvicola terrestris. The findings in these
      fossorial (i.e., burrowing) rodents with components of surface activity were
      compared with respective findings reported for taxonomically related muroid
      rodents representing the same size classes but different eco-morphotypes:
      obligate subterranean rodents (Ellobius talpinus and Spalax ehrenbergi
      superspecies) and generalized rodents (Mus domesticus and Rattus norvegicus). The
      ear in voles was characterized by traits reported for subterranean rodents. The
      eardrum was round, without a distinct pars flaccida, and had an area of 5.4 mm2
      in M. arvalis and 9 mm2 in A. terrestris. The middle ear exhibited reduced
      goniale, enlarged incus nearly parallel to the manubrium of the malleus. The
      malleus-incus lever ratio amounted to 2.1 (M. arvalis) and 2.0 (A. terrestris).
      The malleus-incus complex weighed about 0.8 mg in both vole species. The
      stapedial footplate had an area of 0.3 mm2 in M. arvalis and 0.4 mm2 in A.
      terrestris. The cochlea had 2.3 coils in both vole species; the basilar membrane
      was 8.5 mm and 10.5 mm long in M. arvalis and A. terrestris, respectively. There
      were on average 1,030 (M. arvalis) and 1,220 (A. terrestris) inner hair cells,
      and 3,760 (M. arvalis) and 4,250 (A. terrestris) outer hair cells in the organ of
      Corti. In quantitative terms, all these (as well as some further) traits and
      parameters were intermediate (related to body size) between those reported for
      generalized rodents on the one hand and subterranean ones on the other. The sound
      transmission system of the ear seems to be best tuned to frequencies of about 8
      16 kHz with a high-frequency cut-off at about 50-60 kHz. The ear of A. terrestris
      seems to be tuned to somewhat lower frequencies than that in M. arvalis. In this
      aspect as well as regarding hearing sensitivity (as judged from the mechanical
      transmission parameters), voles can be considered intermediate not only in their
      lifestyle but also in their hearing abilities between the subterranean rodents
      (mole-vole and blind mole-rat) and the surface dwellers (house mouse and Norway
      rat).

PMID- 15487006
TI  - Mutational analysis of BARHL1 and BARX1 in three new patients with Joubert
      syndrome.

PMID- 15487007
TI  - Ultrastructure of posterior sternal glands of Macrotermes annandalei (Silvestri):
      new members of the sexual glandular set found in termites (Insecta).
AB  - In female alates of Macrotermes annandalei, two types of abdominal glands are
      involved in the secretion of sex pheromone. Tergal glands are found at the
      anterior margin of tergites 6-10 and posterior sternal glands (PSGs) are located
      at the anterior margin of sternites 6-7. The cytological features of both types
      of glands are quite similar. The fine structural organization of PSGs is studied
      more precisely and described for the first time. The glandular cuticle is pitted
      with narrow apertures corresponding to the openings of numerous subcuticular
      pouches. Several Class 3 glandular units open in each pouch. One canal cell and
      one secretory cell make an individual glandular unit. The canal cell is enlarged
      apically and is connected with the other canal cells to form a common pouch.
      Based on the structural features found in these glands, we propose a common
      secretory process for PSGs and tergal glands. During the physiological maturation
      of alates inside the nest, secretory vesicles amass in the cytoplasm of secretory
      cells, while large intercellular spaces collapse the cuticular pouches. At the
      time of dispersal flight, pouches are filled with the content of secretory
      vesicles while intercellular spaces are sharply reduced. After calling behavior,
      no secretion remains in the glands and pouches collapse again, while secretory
      cells are drastically reduced in size. The structure and the secretory processes
      of PSGs and tergal glands are compared to those of abdominal sexual glands known
      in termites.

PMID- 15487008
TI  - Living with achondroplasia: quality of life evaluation following cervico
      medullary decompression.
AB  - Achondroplasia is the most common of the heritable skeletal dysplasias. Cervico
      medullary compression is a frequently encountered and potentially lethal
      neurological complication. Cervico-medullary decompression (CMD) at the foramen
      magnum is often employed to relieve the pressure on the emerging cervical cord.
      Given the inherent risks associated with major surgery, there has been a
      substantial debate regarding the best criteria for CMD. Our objectives for this
      study are to explore the quality of life of patients who had undergone CMD, and
      to assess whether surgery is associated with mortality and increased long-term
      morbidity. A Medical Outcome Study 36-item Short Form General Health Survey
      designed to evaluate eight general health concepts as well as achondroplasia
      related issues, was administered to patients assessed in the neurosurgery
      department in Johns Hopkins Hospital between 1977 and 1998. One hundred and sixty
      seven patients were eligible for inclusion. Forty-three could not be contacted,
      and two refused consent. One hundred and twenty-two patients were assessed. Fifty
      six (46%) individuals had CMD and 66 (54%) did not. There was 1 case of mortality
      in the CMD group and 12 cases in the non-CMD group. In the non-CMD group, all
      deaths, as far as we know, were unrelated to cervico-medullary compression. In
      this cohort of surviving patients (n = 109), the quality of life of the 55
      (50.5%) who had undergone CMD is comparable to that of the 54 (49.5%) who did not
      have surgery, controlled for age and sex. CMD is indicated for patients with
      achondroplasia with significant symptomatic foramen magnum compression. It can be
      life saving. It can abolish profound central apnea that may cause sudden death
      and alleviate neurological complications associated with damage of the
      significantly compressed spinal cord. With regards to long-term outcome
      evaluation, the quality of life of individuals with achondroplasia who had CMD is
      similar to those age- and sex-matched patients who did not have this surgery.
      Moreover, CMD, with all its inherent surgical risks, does not appear to be
      associated with higher mortality or increased long-term morbidity.

PMID- 15487009
TI  - Phenotypic manifestations of the OCTN2 V295X mutation: sudden infant death and
      carnitine-responsive cardiomyopathy in Roma families.
AB  - In two non-consanguineous Hungarian Roma (Gypsy) children who presented with
      cardiomyopathy and decreased plasma carnitine levels, we identified homozygous
      deletion of 17081C of the SLC22A5 gene that results in a frameshift at R282D and
      leads ultimately to a premature stop codon (V295X) in the OCTN2 carnitine
      transporter. Carnitine treatment resulted in dramatic improvement of the cardiac
      symptoms, echocardiographic, and EKG findings in both cases. Family
      investigations revealed four sudden deaths, two of them corresponded to the
      classic SIDS phenotype. In postmortem tissue specimens available from three of
      them we could verify the homozygous mutation. In liver tissue reserved from two
      patients lipid droplet vacuolization could be observed; the lipid vacuoles were
      located mainly in the peripherolobular regions of the acini. In the heart tissue
      signs of generalized hypertrophy and lipid vacuoles were seen predominantly in
      the subendocardial areas in both cases; some aggregates of smaller lipid vacuoles
      were separated, apparently by membranes. Review of all OCTN2 deficiency cases
      reported so far revealed that this is the first presentation of histopathology in
      classic familial sudden infant death syndrome (SIDS) with an established SLC22A5
      mutation. In addition to the two affected homozygous cardiomyopathic children and
      three homozygous sudden death patients, the genetic analysis in 25 relatives
      showed 14 carriers. The mutant gene derived from five non-consanguineous
      grandparents, each of them having 6-14 brothers and sisters. This alone suggests
      a wide ancestral spread of the mutation in certain Roma subpopulations.

PMID- 15487010
TI  - Total is more than the sum of the parts: phenotyping the heart in cardiovascular
      genetics clinics.

PMID- 15487011
TI  - Absence of deletion at the SOX2 locus in a case of microphthalmia and esophageal
      atresia.

PMID- 15487012
TI  - Abnormalities of sensory processing and sensorimotor interactions in secondary
      dystonia: a neurophysiological study in two patients.
AB  - Experimental data suggest that abnormalities of sensory processing and
      sensorimotor integration may play a role in the genesis of symptoms in primary
      dystonia. We studied 2 patients with dystonia secondary to lesions in the
      somatosensory pathways. We documented sensorimotor alterations in these patients
      that strongly resemble those found in primary dystonia. Our data are consistent
      with the hypothesis that abnormalities in sensorimotor processing may contribute
      to the pathogenesis of dystonic conditions.

PMID- 15487013
TI  - Derivatization of phosphorylated peptides with S- and N-nucleophiles for enhanced
      ionization efficiency in matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - The identification of phosphorylation sites is essential for a full understanding
      of the cellular functions of proteins. However, mass spectrometric analysis is
      often hampered by the low abundance of phosphoproteins, the difficulty of
      obtaining full sequence coverage by specific proteolysis reactions, and the low
      ionization efficiency of phosphopeptides compared with their non-phosphorylated
      analogs. In the present work a beta-elimination/Michael addition was used to
      replace the phosphate groups of pSer or pThr by a group which gives rise to an
      enhanced ionization efficiency. In order to find optimum reaction conditions,
      beta-elimination/Michael addition was examined using phosphorylated model
      peptides. Whereas complete elimination of phosphate could be achieved by
      treatment with barium hydroxide in organic solvents such as ethanol or
      acetonitrile, the yield of the Michael adduct strongly depended on the
      nucleophile and the peptide sequence. Reaction with 2-phenylethanethiol, p
      bromophenethylamine and ethylenediamine clearly resulted in products showing
      higher matrix-assisted laser desorption/ionization (MALDI) signal intensities
      compared with those of the corresponding phosphorylated precursors. The method
      was successfully used to identify phosphorylated sequences of ovalbumin and human
      Stat1 by in-gel derivatization with 2-phenylethanethiol and subsequent peptide
      mass fingerprint analysis of the trypsin digests.

PMID- 15487014
TI  - Different pathways mediated by CCK1 and CCK2 receptors: effect of intraperitonal
      mrna antisense oligodeoxynucleotides to cholecystokinin on anxiety-like and
      learning behaviors in rats.
AB  - Cholecystokinin (CCK) and its analogs generate anxiety in humans and measurable
      anxiety-like behaviors in rats. CCK receptor blockers have been reported to have
      variable effects in the treatment of anxiety disorders. In a prior study,
      intracerebroventricular administration of CCK-antisense oligodeoxynucleotides
      (ASODN) for 3 days significantly diminished anxiety-like behavior in rats.
      Counter to our expectations, intraperitoneal (i.p.) administration of CCK-ASODN
      significantly increased anxiety-like behavior and impaired retention performance
      in the Morris water maze. The aim of the present study was to manipulate CCK
      mediated anxiety-like behavior and spatial memory in rats by peripheral (i.p.)
      administration of ASODN to preproCCK in the presence of antagonists to CCK1 and
      CCK2 receptor subtypes to further elucidate the roles of these two receptors and
      better understand the effects of i.p. CCK-ASODN. CCK-ASODN was injected i.p. to
      rats five times at 24-hr intervals with and without administration of CCK1R
      antagonist PD135158 or CCK2 antagonist benzotrip. Control groups received
      injections of either a scrambled oligodeoxynucleotide (ScrODN) or vehicle. On Day
      6, the rats were assessed in the elevated plus maze paradigm and in the Morris
      water maze. The rats were sacrificed and their blood was assessed for
      corticosterone, ACTH, and prolactin levels. The results show that i.p. CCK-ASODN
      significantly increased anxiety-like behavior and impaired retention performance
      in the Morris water maze, compared to both control groups, accompanied by
      increased plasma corticosterone and plasma ACTH concentrations. In contrast,
      administration of CCK-ASODN together with CCK2R antagonist, but not with CCK1R
      antagonist, significantly decreased anxiety-like behavior in rats, but still
      impaired retention performance in the Morris water maze paradigm. Lower levels of
      plasma corticosterone and ACTH in CCK-ASODN+CCK2R antagonist-treated rats
      accompanied the reduced anxiety-like behavior. The present study showed an
      anxiolytic effect of i.p. CCK-ASODN in the presence of CCK2R, but not CCK1R.

PMID- 15487015
TI  - Differences in course and comorbidity of recurrent depression in primary care and
      psychiatric populations.

PMID- 15487016
TI  - Anatomy of the pharyngeal jaw apparatus of Zenarchopterus (gill) (Teleostei:
      Beloniformes).
AB  - The structure of the pharyngeal jaw apparatus (PJA) of Zenarchopterus dispar and
      Z. buffonis, carnivorous estuarine and freshwater West-Pacific halfbeaks, was
      investigated using dissection, light, and scanning electron microscopy as part of
      a comparison with estuarine and marine herbivorous confamilials. The
      Zenarchopterus PJA differs from published descriptions of hemiramphid PJAs in
      that the otic capsules are less pronounced; the pharyngocranial articulation
      facet is trough-like; the third pharyngobranchials are ankylosed; the second
      pharyngobranchial anterior processes are relatively hypotrophied; all pharyngeal
      teeth except the posterior teeth in the fifth ceratobranchial face posteriorly;
      the muscularis craniopharyngobranchialis 2 posterior is short; the muscularis
      craniopharyngobranchialis 2 anterior is lacking, as is its insertion site, the
      inferior parasphenoid apophysis; the protractor pectoralis is well developed; the
      pharyngocleithralis internus originates dorsal to the level of the fifth
      ceratobranchial bony process; the fifth ceratobranchial bony processes are
      directed ventrolaterally; the opposing upper and lower tooth fields appear not to
      occlude erosively; and the muscular portion of the pharyngohyoideus is well
      developed anteriorly. The extent of these differences and their implications for
      the function of the PJA support recent molecular studies that suggest that the
      Hemiramphidae is polyphyletic.

PMID- 15487017
TI  - Gender differences in anxiety-related traits in patients with panic disorder.
AB  - This study examined gender differences in anxiety-related personality traits in
      patients with panic disorder with or without agoraphobia (PD+/-AG). Outpatients
      (101 total) with SCID confirmed PD+/-AG completed the Anxiety Sensitivity Index
      (ASI), the Trait form of the State-Trait Anxiety Inventory (STAI-T), the NEO
      Personality Inventory Revised (NEO PI-R), and the Retrospective Self-Report of
      Inhibition (RSRI) as part of their assessment. Significant gender differences
      were not detected for the total ASI scores. Females scored significantly higher
      than males on the Physical Concerns subscale of the ASI, whereas males scored
      significantly higher than women on the Social Concerns subscale. Women scored
      higher than men on the Extraversion scale of the NEO PI-R as well as on certain
      subscales of this domain. Although a significant gender difference was not
      detected on the Neuroticism subscale, men scored higher on the angry hostility
      and depression facets of this trait. Significant gender differences were not
      found for the STAI-T or the RSRI. These findings suggest that gender differences
      exist among patients with PD+/-AG in the feared consequences of anxiety symptoms
      as well as in the personality characteristics of extraversion.

PMID- 15487018
TI  - Morphological observation of antler regeneration in red deer (Cervus elaphus).
AB  - Deer antler offers a unique opportunity to explore how nature solves the problem
      of mammalian appendage regeneration. Annual antler renewal is an example of
      epimorphic regeneration, which is known to take place through initial blastema
      formation. Detailed examination of the early process of antler regeneration,
      however, has thus far been lacking. Therefore, we conducted morphological
      observations on antler regeneration from naturally cast and artificially created
      pedicle/antler stumps. On the naturally cast pedicle stumps, early antler
      regeneration underwent four distinguishable stages (with the Chinese equivalent
      names): casting of previous hard antlers (oil lamp bowl), early wound healing
      (tiger eye), late wound healing and early regeneration (millstone), and formation
      of main beam and brown tine (small saddle). Overall, no cone-shaped regenerate, a
      common feature to blastema-based regeneration, was observed. Taken together with
      the examination on the sagittal plane of each regenerating stage sample, we found
      that there are considerable overlaps between late-stage wound healing and the
      establishment of posterior and anterior growth centers. Observation of antler
      regeneration from the artificially created stumps showed that the regeneration
      potential of antler remnants was significantly reduced compared with that of
      pedicle tissue. Interestingly, the distal portion of a pedicle stump had greater
      regeneration potential than the proximal region, although this differential
      potential may not be constitutive, but rather caused by whether or not pedicle
      antlerogenic tissue becomes closely associated with the enveloping skin at the
      cut plane. Antler formation could take place from the distal peripheral tissues
      of an antler/pedicle stump, without the obvious participation of the entire
      central bony portion. Overall, our morphological results do not support the
      notion that antler regeneration takes place through the initial formation of a
      blastema; rather, it may be a stem cell-based process.

PMID- 15487019
TI  - Glial fibrillary acidic protein and vimentin immunoreactivity of astroglial cells
      in the central nervous system of the African lungfish, Protopterus annectens
      (Dipnoi: Lepidosirenidae).
AB  - The distribution of glial intermediate filament molecular markers, glial
      fibrillary acidic protein (GFAP), and vimentin, in the brain and spinal cord of
      the African lungfish, Protopterus annectens, was examined by light microscopy
      immunoperoxidase cytochemistry. Glial fibrillary acidic protein immunoreactivity
      is clear and is evident in a radial glial system. It consists of fibers of
      different lengths and thicknesses that are arranged in a regular radial pattern
      throughout the central nervous system (CNS). They emerge from generally
      immunopositive radial ependymoglia (tanycytes), lining the ventricular surface,
      and are directed from the ventricular wall to the meningeal surface. These fibers
      give rise to endfeet that are apposed to the subpial surface and to blood vessel
      walls forming the glia limitans externa and the perivascular glial layer,
      respectively. GFAP-immunopositive star-shaped astrocytes were not found in P.
      annectens CNS. In the gray matter of the spinal cord, cell bodies of
      immunopositive radial glia are displaced from the ependymal layer. Vimentin
      immunopositive structures are represented by thin fibers mostly localized in the
      peripheral zones of the brain and the spinal cord. While a few stained fibers
      appear in the gray matter, the ependymal layer shows no antivimentin
      immunostaining. In P. annectens the immunocytochemical response of the astroglial
      intermediate filaments is typical of a mature astroglia cell lineage, since they
      primarily express GFAP immunoreactivity. This immunocytochemical study shows that
      the glial pattern of the African lungfish resembles that found in tetrapods such
      as urodeles and reptiles. The glial pattern of lungfishes is comparable to that
      of urodeles and reptiles but is not as complex as that of teleosts, birds, and
      mammals.

PMID- 15487020
TI  - Intracranial portion of the trochlear nerve and dorsal oblique muscle composition
      in dog: a structural and ultrastructural study.
AB  - In the present investigation the right intracranial portion of the trochlear
      nerves and dorsal oblique muscle of the right ocular globe were removed from six
      adult dogs and analyzed by light and electron microscopy. Unmyelinated fibers
      were observed in the analyzed nerves. The number, diameter, area, and density of
      myelinated fibers were determined, as were corresponding axon area and diameter
      and myelin sheath thickness. Frequency histograms of myelin sheath thickness and
      fiber size show a bimodal distribution with a similar proportion of large and
      small fibers. Muscle samples were taken from the central portion of the muscle
      belly, subsequently frozen, cut, and stained with m-ATPase at pH 4.6. Fibers were
      classified as Type 1 or Type 2 according to their reaction to the m-ATPase and
      detailed morphologic and morphometric studies were made. The muscles showed two
      clearly distinct layers, a central layer and a peripheral layer, chiefly composed
      of Type 2 fibers. The fibers in the central layer were larger in size than those
      in the peripheral layer.

PMID- 15487021
TI  - Ultrastructure of the reproductive system of the black swamp snake (Seminatrix
      pygaea). IV. Occurrence of an ampulla ductus deferentis.
AB  - The distal end of the ductus deferens of Seminatrix pygaea (Cope) differs from
      more proximal portions of the tube by possessing a highly fluctuated epithelium.
      Similar morphology has been reported in this area in one lizard and some mammals
      and the region has been designated in these taxa as the ampulla ductus
      deferentis. In this study, light and transmission electron microscopy were used
      to study the posterior ductus deferens in S. pygaea and compare the histology in
      this region to more proximal regions of the duct and to descriptions of the
      ampulla of other species. Seminatrix pygaea stores sperm throughout the ductus
      deferens during the entire year. The epithelium of the ductus deferens is not
      secretory, but the presence of numerous small apical vesicles indicates a role in
      fluid absorption. In addition to the highly folded epithelium, clusters of sperm
      nuclei are more intimately associated with the apical ampullary epithelium than
      elsewhere in the ductus deferens. No evidence of phagocytosis of sperm was found.
      In contrast, the ampulla of mammals and presumably the lizard Calotes versicolor
      is glandular and phagocytic. The common character shared by the squamates and
      mammals with specializations in this area is the folded epithelium, and whether
      this is due to shared ancestry with amniotes or is homoplastic is unresolved.

PMID- 15487022
TI  - A study on biomineralization behavior of N-methylene phosphochitosan scaffolds.
AB  - Biomimetic growth of calcium phosphate over natural polymer may be an effective
      approach to constituting an organic/inorganic composite scaffold for bone tissue
      engineering. In this work, N-methylene phosphochitosan (NMPCS) was prepared via
      formaldehyde addition and condensation with phosphoric acid in a step that
      allowed homogeneous modification without obvious deterioration in chitosan (CS)
      properties. The NMPCS obtained was characterized by using FT-IR and elemental
      analysis. The macroporous scaffolds were fabricated through a freeze-drying
      technique. A comparative study on NMPCS and CS scaffold biomimetic mineralization
      was carried out in different media, i.e, a simulated body fluid (SBF) or
      alternative CaCl(2) and Na(2)HPO(4) solutions respectively. Apatite formation
      within NMPCS and CS scaffolds was identified with FT-IR, scanning electron
      microscopy (SEM), energy-dispersive X-ray (EDX) and X-ray diffractometery (XRD).
      The results revealed alternate soaking of the scaffolds in CaCl(2) and
      Na(2)HPO(4) solutions was better than soaking in SBF solution alone in relation
      to apatite deposition on the scaffold pore walls. Biomineralization provides an
      approach to improve nature derived materials, e.g., chitosan derivative NMPCS
      properties e.g., compressive modulus, etc. SEM image of a NMPCS/apatite composite
      scaffold.

PMID- 15487023
TI  - Tailored noise waveform/collision-induced dissociation of ions stored in a linear
      ion trap combined with liquid chromatography/Fourier transform ion cyclotron
      resonance mass spectrometry.
AB  - A new collision-induced dissociation (CID) technique based on broadband tailored
      noise waveform (TNW) excitation of ions stored in a linear ion trap has been
      developed. In comparison with the conventional sustained off-resonance
      irradiation (SORI) CID method commonly used in Fourier transform ion cyclotron
      resonance mass spectrometry (FTICR-MS), this MS/MS technique increases throughput
      by eliminating the long pump-down delay associated with gas introduction into the
      high vacuum ICR cell region. In addition, the TNW-CID method speeds spectrum
      acquisition since it does not require Fourier transformation, calculation of
      resonant frequencies and generation of the excitation waveforms. We demonstrate
      TNW-CID coupled with on-line capillary reverse-phase liquid chromatography
      separations for the identification of peptides. The experimental results are
      compared with data obtained using conventional quadrupole ion trap MS/MS and SORI
      CID MS/MS in an ICR cell.

PMID- 15487024
TI  - Identification of intact long-chain p-hydroxycinnamate esters in leaf fibers of
      abaca (Musa textilis) using gas chromatography/mass spectrometry.
AB  - The study of acetone-extractable components from the leaf fibers of the non-wood
      plant abaca (Musa textilis) resulted in the isolation and identification of
      series of intact hydroxycinnamate esters consisting of ferulic and p-coumaric
      acids esterified to long-chain fatty alcohols (C20 to C28) and omega-hydroxyfatty
      acids (C22 to C28). These series of compounds were characterized by high
      temperature gas chromatography/mass spectrometry (GC/MS) using capillary columns
      (12 m length) with thin films that allowed the analysis of intact (i.e., without
      prior saponification) hydroxycinnamate esters. Characterization of intact
      individual compounds was achieved based on the mass spectra obtained by GC/MS of
      the underivatized compounds and their methyl and/or trimethylsilyl ether
      derivatives.

PMID- 15487025
TI  - Novel hypervalent complexes of main-group metals by intramolecular ligand-->metal
      electron transfer.
AB  - New fascinating electronic features of the simple diketoamine chelate ligand
      HN[CH2C(tBu)=O]2 (1) are described. Unexpectedly, the corresponding trianionic
      amido-dienolate form of 1 is capable of reducing main-group metal atoms M after
      initial coordination and intramolecular L-->M two-electron transfer and of
      stabilizing main-group elements in unusual low oxidation states. This is
      impressively shown by the synthesis and structural characterization of the novel
      Ge and Sn complexes 4-6 by redox reactions of lithiated 1 with the corresponding
      metal halides GeCl4 and MCl2 (M=Ge, Sn). Surprisingly, conversion of tris
      lithiated 1 with GeCl4 readily consumes two molar equivalents of GeCl4 and
      results in the formation of the neutral GeCl3 complex 4 and GeCl2. The former
      represents the second example of a structurally characterized neutral
      octahedrally coordinated germanium compound. Reaction of dilithiated 1 with GeCl2
      does not lead to the expected ClGe(+2) complex but affords the novel dimeric
      germylene 5, whereas similar reaction using SnCl2 furnishes the monomeric
      stannylene (ClSn(+2) complex) 2 and elemental tin due to the higher oxidation
      potential of Sn(+2). Unexpectedly, a similar redox reaction of dilithiated 1 with
      PbCl2 furnishes the first air- and water-stable lithium 1,2-diketoimine-enolate 7
      and elemental lead. Compound 7 is tetrameric in the solid state and consists of a
      strongly distorted Li4O4 cubic core with trigonal-bipyramidal coordinated Li+
      ions.

PMID- 15487026
TI  - Controlling degradation of acid-hydrolyzable pluronic hydrogels by physical
      entrapment of poly(lactic acid-co-glycolic acid) microspheres.
AB  - Chemically crosslinked biodegradable hydrogels based on di-acrylated Pluronic F
      127 tri-block copolymer were prepared by a photopolymerization method.
      Poly(lactic acid-co-glycolic acid) (PLGA) microspheres were physically entrapped
      within the Pluronic hydrogel in order to modulate the local pH environment by
      acidic degradation by-products of PLGA microspheres. The PLGA microspheres were
      slowly degraded to create an acidic microenvironment, which facilitated the
      cleavage of an acid-labile ester-linkage in the biodegradable Pluronic hydrogel
      network. The presence of PLGA microspheres accelerated the degradation of the
      Pluronic hydrogel and enhanced the protein release rate when protein was loaded
      in the hydrogel.SEM image of photo-crosslinked Pluronic hydrogel entrapping PLGA
      microspheres.

PMID- 15487027
TI  - Enantioselective catalysis of the hetero-Diels-Alder reaction between Brassard's
      diene and aldehydes by hydrogen-bonding activation: a one-step synthesis of (S)
      (+)-dihydrokawain.
AB  - The first catalytic enantioselective hetero-Diels-Alder reaction between
      Brassard's diene and aldehydes has been achieved through hydrogen-bonding
      activation using TADDOL derivatives as catalysts to afford the corresponding
      delta-lactone derivatives in moderate-to-good yields and with high
      enantioselectivities (up to 91 % ee). The reactions can be carried out either
      under solvent-free conditions or in toluene. On the basis of the absolute
      configurations of the products and the hydrogen-bonding interaction pattern
      between TADDOL (alpha,alpha,alpha',alpha'-tetraaryl-1,3-dioxolan-4,5-dimethanol)
      and the carbonyl group disclosed by X-ray diffraction analysis, a possible
      mechanism for the catalytic reaction has been proposed. To demonstrate the
      usefulness of the methodology, a natural product, (S)-(+)-dihydrokawain, has also
      been prepared in 50 % isolated yield and with 69 % enantioselectivity in one step
      starting from 3-phenylpropionaldehyde by using this methodology. Therefore, this
      catalytic system is one of the most direct approaches to the construction of
      delta-lactone units, which will make the methodology very attractive for the
      synthesis of a variety of biologically important compounds and natural products.

PMID- 15487028
TI  - New types of soluble polymer-supported bisphosphine ligands with a cyclobutane
      backbone for Pd-catalyzed enantioselective allylic substitution reactions.
AB  - A highly efficient and practical optical resolution of anti head-to-head racemic
      coumarin dimer 7 has been achieved by molecular complexation with TADDOL, (-)-8,
      through a hydrogen bonding interaction to afford the corresponding two
      enantiomers, (-)- and (+)-7, in 70 and 75 % yields, respectively, with >99 % ee.
      Starting from enantiopure (-)-7, a new type of C2-symmetric bisphosphine ligand
      (S,S,S,S)-3 with a cyclobutane backbone has been synthesized in good yield by
      facile transformations. The asymmetric induction efficiency of these chiral
      bisphosphine ligands in Pd-catalyzed asymmetric allylic substitution reactions
      was evaluated. Under the experimental conditions, the allylic substitution
      products could be obtained in excellent yields (up to 99 %) and
      enantioselectivities (up to 98.9 % ee). By taking advantage of the high
      enantioselectivity of this catalytic reaction and the easily derivable
      carboxylate groups on the cyclobutane backbone of ligand (S,S,S,S)-3, a new type
      of analogous ligand (S,S,S,S)-4 as well as the MeO-PEG-supported soluble ligand
      (S,S,S,S)-5 (PEG=polyethylene glycol) have also been synthesized and utilized in
      asymmetric allylic substitution reactions. In particular, the MeO-PEG supported
      (S,S,S,S)-5 b had a synergistic effect on the enantioselectivity of the reaction
      compared with its nonsupported precursor (S,S,S,S)-4 c, affording the
      corresponding allylation products 14 a and 14 b with excellent
      enantioselectivities (94.6 and 97.2 % ee, respectively). Moreover, the Pd complex
      of (S,S,S,S)-5 b could easily be recovered and recycled several times without
      significant loss of enantioselectivity and activity in the allylic substitution
      reactions.

PMID- 15487029
TI  - Theoretical studies of aluminoxane chains, rings, cages, and nanostructures.
AB  - Alumina nanostructures and three families of aluminoxanes, linear, cyclic, and
      cagelike structures, have structures that resemble their isovalent electronic
      hydrocarbon analogues. Specific examples of each family are the counterparts of
      fullerene, allene, benzene, and cubane, respectively. The aluminoxanes and
      alumina nanostructures are related to each other; the latter can be regarded as a
      hydrogen- or alkyl-free form of aluminoxane. By exploiting this relationship, the
      relative stabilities of the three families of aluminoxanes, alumina
      nanostructures, and alumina crystal lattices have been estimated. According to ab
      initio calculations, aluminoxane cages, which take the form of a truncated
      octahedron and related polyhedra, are favored. The stability of the preferred
      cage, T-symmetric Al28O28H28, is practically equal to that of the alpha-alumina
      crystal lattice.

PMID- 15487030
TI  - Catalytic photooxidation of 4-methoxybenzyl alcohol with a flavin-zinc(II)-cyclen
      complex.
AB  - Flavin-zinc(II)-cyclen 10 contains a covalently linked substrate binding site
      (zinc(II)-cyclen) and a chromophore unit (flavin). Upon irradiation, compound 10
      effectively oxidizes 4-methoxybenzyl alcohol (11-OCH3) to the corresponding
      benzaldehyde both in water and in acetonitrile. In the presence of air, the
      reduced flavin 10-H2 is reoxidized, and so catalytic amounts of 10 are sufficient
      for alcohol conversion. The mechanism of oxidation is based on photoinduced
      electron transfer from the coordinated benzyl alcohol to the flavin chromophore.
      This intramolecular process provides a much higher photooxidation efficiency,
      with quantum yields 30 times those of the comparable intermolecular process with
      a flavin chromophore without a binding site. For the reaction in buffered aqueous
      solution a quantum yield of Phi = 0.4 is observed. The turnover number in
      acetonitrile is increased (up to 20) by high benzyl alcohol concentrations. The
      results show that the covalent combination of a chromophore and a suitable
      binding site may lead to photomediators more efficient than classical sensitizer
      molecules.

PMID- 15487031
TI  - Translational control at the synapse.
AB  - The strength of synaptic connections can undergo long-lasting changes, and such
      long-term plasticity is thought to underlie higher brain functions such as
      learning and memory. De novo synthesis of proteins is required for such plastic
      changes. This model is now supported by several lines of experimental data.
      Components of translational machinery have been identified in dendrites,
      including ribosomes, translation-al factors, numerous RNAs, and components of
      posttranslational secretory pathways. Various RNAs have been shown to be actively
      and rapidly transported to dendrites. Dendritic RNAs typically contain transport
      specifying elements (dendritic targeting elements). Such dendritic targeting
      elements associate with trans-acting factors to form transport-competent
      ribonucleoprotein particles. It is assumed that molecular motors mediate
      transport of such particles along dendritic cytoskeletal elements. Once an mRNA
      has arrived at its dendritic destination site, appropriate spatiotemporal control
      of its translation, for example, in response to transsynaptic activity, becomes
      vital. Such local translational control, recent evidence indicates, is
      implemented at different levels and through various pathways. In the default
      state, translation is assumed to be repressed, and several mechanisms, some
      including small untranslated RNAs, have been proposed to contribute to such
      repression. Translational control at the synapse thus provides a molecular basis
      for the long-term, input-specific modulation of synaptic strength.

PMID- 15487032
TI  - Vascular adaptation to microgravity.

PMID- 15487033
TI  - [Therapy of painful bone metastases in patients with prostate carcinoma. The AP
      32/02 Study of the AUO].

PMID- 15487034
TI  - [The regional hospital--still of importance?].

PMID- 15487035
TI  - [Docetaxel enables initial survival time lengthening].

PMID- 15487036
TI  - Frequency and clinical course of hepatitis E in tertiary care hospitals.
AB  - OBJECTIVE: To find out the frequency of hepatitis E virus as a cause of acute
      hepatitis and its clinical course in hospitalized patients. DESIGN: Cross
      sectional hospital-based study. PLACE AND DURATION OF STUDY: The study was
      conducted in two tertiary care teaching hospitals i.e., Khyber Teaching Hospital
      and PGMI Lady Reading Hospital, Peshawar (Pakistan) from January to December
      2002. PATIENTS AND METHODS: Amongst the total number of 1922 admitted patients,
      148 had history of nausea, vomiting and jaundice and raised serum bilirubin with
      raised hepatic transaminases (ALT), were screened for HBV (hepatitis B virus),
      HCV (hepatitis C virus) and subsequently for HEV (hepatitis E virus). Acute
      hepatitis A, autoimmune hepatitis and Wilson's disease were excluded by doing
      appropriate test as and when required. The patients with hepatitis E were then
      monitored by checking their serial transaminases on day 1,4,8 and day 18 or until
      their transaminases dropped to normal. They were also clinically assessed and
      followed-up. RESULTS: Amongst the total admission of 1922 patients during one
      year period, 148 had acute hepatitis and out of these, 21 patients (14.189%)
      suffered from hepatitis E. Seventeen patients were below the age of 40. There
      were increased number of cases during the late summer and early winter seasons.
      Majority of the hepatitis E patients recovered during the short follow-up period
      of two weeks. Two patients had fulminant hepatitis. A four months pregnant young
      female died of her illness despite intensive treatment. CONCLUSION: Hepatitis E
      virus is fairly common cause of acute hepatitis in hospitalized patients. Most of
      the patients are having a benign self-limiting illness.

PMID- 15487037
TI  - [Therapy of tumor associated hypercalcemia].

PMID- 15487038
TI  - Mechanisms of action of tumor necrosis factor antagonist and granulomatous
      infections.

PMID- 15487039
TI  - [Bacillus calmette-guerin and its derivatives in the treatment of asthma].

PMID- 15487040
TI  - The role of industry in improving quality of life for persons with an ostomy: a
      Canadian consensus.
AB  - Financial and clinical resources (which include 260 enterostomal therapy nurses
      nationwide) to provide clinical and rehabilitative expertise to the estimated
      50,000 to 60,000 Canadians living with an ostomy are limited. Hence, many persons
      with an ostomy fall through the cracks in the early pre- and postoperative period
      or are lost to follow-up afterdischarge. Problems and issues related to ostomy
      management continue to surface throughout their lives. As a result,the time
      required for rehabilitation is often lengthy, affecting the person's quality of
      life. The First Canadian Enterostomal Therapy Nurses' Advisory Council consisting
      of 10 Canadian enterostomal therapy nurses met in February 2004 to identify key
      issues and concerns for Canadians living the ostomy experience and to identify
      gaps in information and services available before surgery, during the immediate
      postoperative period, and as the time from surgery lengthened and patients moved
      through age-related life issues. The two most important gaps identified were the
      development of quality, pertinent resources and the dissemination of those
      resources. The Council also identified potential strategies to bridge these gaps,
      including utilizing the resources of manufacturer Customer Service departments to
      follow a communications protocol to provide information to patients, retailers,
      and providers. Finally, a process map from which individual ostomy manufacturers
      can build programs and processes for improving patient/provider/manufacturer
      communication was developed.

PMID- 15487041
TI  - Sensitivity and spectrum of bacterial isolates in infectious otitis externa.

PMID- 15487042
TI  - [Rescue and treatment problems of casualties in sudden disaster].

PMID- 15487043
TI  - Advocacy: ASE working for you.

PMID- 15487044
TI  - Neurosurgery in Italy: origins to modernity.

PMID- 15487046
TI  - Mechanisms of fullerene separations.

PMID- 15487045
TI  - [Health situation of the armies in the Crimean war and a document related to
      this].
AB  - Although the Crimean War seems to be a war between the Ottoman and Russian with
      the support of England an France, in reality, it was a power struggle between the
      biggest European countries. The cooperation between England - Ottoman Empire and
      France in the Crimean War meanly determined the result of the war. The Crimean
      War should not only be evaluated in militarian and political aspect, but also
      from other perspectives. One of the most important problems for the allied armies
      in Istanbul and Crimea was related to the health concepts. During the two years
      long war, problems were the freezing cold and contagious diseases before the
      Russian soldiers. And thypus, scorbut, cholera and malaria prepears the dead of a
      large number of soldiers. Although the allied armies won the battle but all the
      sides fighting in the was lost many people due to contagious diseases. According
      to the resources, the contagious diseases such as, thypus, cholera and malaria
      led to the deads of more than ten times of the people who were in the battle
      field. Thats why, The European armies understood the importance of the treatment
      diseases in the war and gave importance to the development of military medical
      services and form this point, the Crimean War became the begining of an important
      development in military health concept.

PMID- 15487048
TI  - Barcoding the microworld.

PMID- 15487049
TI  - IR spectroscopy in clinical and diagnostic applications.

PMID- 15487050
TI  - Use of a microscope objective corrected for a cover glass to improve confocal
      spatial resolution inside a sample with a finite index of refraction.

PMID- 15487052
TI  - Portable FTIR spectrometers get moving.

PMID- 15487051
TI  - Using dispersion to detect binding.

PMID- 15487053
TI  - An exodus of African nurses puts infants and the ill in peril.

PMID- 15487054
TI  - [The life and surgical accomplisment of Dr. Murat Cankat].
AB  - Dr. Murat Cankat is one of the most important figures of the history of surgery
      in Turkey. Dr. Cankat worked many years in Gulhane Hospital and applied several
      neurosurgical interventions. In this study the neurosurgical studies, manuscripts
      and books of Dr. Cankat were reviewed.

PMID- 15487055
TI  - As a life ebbs, the ultimate family quarrel.

PMID- 15487056
TI  - Feed-tube law is struck down in Florida case.

PMID- 15487057
TI  - For women worried about fertility, egg bank is a new option.

PMID- 15487058
TI  - Unblame the victim: heart disease causes vary.

PMID- 15487059
TI  - Give up? No way. On a matter of life or death, a patient is overruled.

PMID- 15487060
TI  - The kidney swap: adventures in saving lives.

PMID- 15487061
TI  - [Memories of some Turkish doctors of XIXth and XXth centuries].

PMID- 15487062
TI  - By accident, Utah is proving an ideal genetic laboratory.

PMID- 15487063
TI  - A stranger in the mirror: should doctors transplant faces?

PMID- 15487064
TI  - English lab ready to clone embryos for stem cells.

PMID- 15487065
TI  - Selling prescription drugs to the consumer: with Vioxx's withdrawal, new
      questions on a $3.8 billion ad business.

PMID- 15487066
TI  - [Lamivudine treatment for hepatitis B].

PMID- 15487067
TI  - Long-term results after radiosurgery for benign intracranial tumors.

PMID- 15487068
TI  - Tailored operative technique for Chiari type I malformation using intraoperative
      color Doppler ultrasonography.

PMID- 15487069
TI  - Increases in cardiac output can reverse flow deficits from vasospasm independent
      of blood pressure: a study using xenon computed tomographic measurement of
      cerebral blood flow.

PMID- 15487070
TI  - [History of neurosurgery in Turkey].

PMID- 15487071
TI  - Mini-open carpal tunnel decompression.

PMID- 15487072
TI  - "Tangential" resection of medial temporal lobe arteriovenous malformations with
      the orbitozygomatic approach.

PMID- 15487073
TI  - Resident duty hours in American neurosurgery.

PMID- 15487074
TI  - [Another profession in the Ottoman period dealing with pharmaceutics: surgery].
AB  - We have realized in many documents that in the Ottoman period surgeons were
      involved in pharmaceutics as much as physicians and herbalists. Surgeons employed
      by the state ordered more drugs than physicians, and it is interesting that in
      their order list there were mostly singular drugs instead of ready-made ones. In
      addition to drugs used by surgeons in preparing ointments and plasters, pans and
      filters were utilized in the process of production, and earthenware pots, tin and
      wooden boxes with various kinds of paper were ordered for the purpose of
      packaging. We have determined that most of the single drugs placed onto the lists
      of surgeons were "ointment of rust" that dries the pus, and "red ointment" that
      is good for all kinds of pus. The preparation of the ointments were specified in
      detail in books of surgery (Cerrahnames)We have observed that parallel to the
      Regulation of 1826, surgeons were given the title of pharmacist when they were
      appointed to military bodies. 100 kurus (piaster) were paid to surgeons for
      performing surgery and 50 kurus for preparing drugs, which is another important
      document indicating that surgeons were more responsible than physicians in
      preparing drugs.

PMID- 15487075
TI  - Erectile dysfunction and scleroderma.

PMID- 15487076
TI  - [Journal of Darulfunun School of Medicine (1916-1933)].
AB  - In this study one of six academic journals published by Istanbul University,
      Darulfunun Tip Fakultesi Mecmuasi (Journal of Darulfunun School of Medicine), is
      reviewed. This review study covered all issues of the journal published between
      1916 and 1933. Our aim was to determine the publication period of the journal, to
      determine the published papers and their authors, and as a result, to help the
      researchers for study in the field of history of medicine. According to our
      review, 1025 manuscripts were published in 96 issues of Darulfunun Tip Fakultesi
      Mecmuasi. There are many national and international faculties among the authors
      of the papers. The content of the journal included many research papers written
      by Turkish faculties, and translated version of some papers published in
      important international journals. There are also some manuscripts written in
      English or French in the period after 1928. All these studies reveal that School
      of Medicine was aware of the progresses in Europe. The journal was published
      during the World War I and during social reorganization of Turkey. Most of the
      authors of the journal tried to present the western scientific development to the
      physicians and students. This provided an established place for the journal at
      the scientific field of the time, though it was not published regularly. The
      journal reflects the approach of the School of Medicine to the scientific
      progresses. The review of this journal contribute to the school of medicine and
      university historians, as well as it will be resource for the future studies in
      the field of history of medicine.

PMID- 15487077
TI  - An evidence-based approach to reducing bed rest in the invasive cardiology
      patient population.

PMID- 15487078
TI  - Sedation management for the adult mechanically ventilated patient.

PMID- 15487079
TI  - You can make a difference in 5 minutes.

PMID- 15487080
TI  - Music intervention in the intensive care unit: a complementary therapy to improve
      patient outcomes.

PMID- 15487081
TI  - A school based programme to reduce carbonated drink consumption reduced obesity
      in children.

PMID- 15487082
TI  - Review: most selective serotonin reuptake inhibitors lead to adverse events that
      appear to outweigh the benefits in children.

PMID- 15487084
TI  - Review: probiotics reduced diarrhoea at 3 days in children and adults with proven
      or presumed infectious diarrhoea.

PMID- 15487083
TI  - A clinical and spiritual approach to healing.

PMID- 15487085
TI  - Review: brief multicontact behavioural counselling interventions in primary care
      reduce risky or harmful alcohol use.

PMID- 15487086
TI  - [The short history of the Turkish Society of Physical and Natural Sciences].
AB  - The Turkish Society of Physical and Natural Sciences was founded at Istanbul
      University in 1934 by some foreign and Turkish professor to stimute the
      researches in physics and biology. The new advancements in these fields and
      results of the researchs of the members were discussed in sessions and published
      in the transactions and archives of the society, mostly in German with Turkish
      summaries. The Society losted its importance after gradually departure of the
      foreign members from Turkey and particularly foundation independent societies for
      physics and biology. The activity of the Turkish Society of Physical and
      Biological Sciences was terminated in 1954.

PMID- 15487087
TI  - Review: psychological interventions reduce glycated haemoglobin concentrations in
      type 2 diabetes.

PMID- 15487088
TI  - Review: simplifying dosing regimens appears to improve treatment adherence in
      patients with high blood pressure in ambulatory settings.

PMID- 15487089
TI  - Review: existing evidence does not support a survival benefit for women with
      metastatic breast cancer who participate in group psychological interventions
      compared with usual care.

PMID- 15487090
TI  - Review: active compression-decompression CPR has no benefit over standard
      resuscitation for cardiac arrest.

PMID- 15487091
TI  - Superficial venous surgery plus compression reduced ulcer recurrence in chronic
      venous leg ulceration.

PMID- 15487092
TI  - Review: psychological interventions do not reduce all cause or cardiac mortality
      in coronary heart disease.

PMID- 15487093
TI  - Review: comprehensive discharge planning plus post-discharge support reduces
      total readmissions in older patients with congestive heart failure.

PMID- 15487094
TI  - Advanced practice nurse directed transitional care reduced readmission or death
      in elderly patients admitted to hospital with heart failure.

PMID- 15487095
TI  - Review: therapy based rehabilitation services reduce the risk of deterioration in
      patients who have had a stroke.

PMID- 15487096
TI  - Training informal caregivers of patients with stroke improved patient and
      caregiver quality of life and reduced costs.

PMID- 15487097
TI  - Review: prophylactic use of vitamin D reduces falls in older people.

PMID- 15487098
TI  - Severity of cognitive impairment at initial diagnosis of Alzheimer's disease was
      the strongest predictor of survival.

PMID- 15487099
TI  - Routine childhood vaccinations did not increase the risk of incident type 1
      diabetes in Danish children.

PMID- 15487100
TI  - Review: spontaneous or induced abortion is not associated with development of
      breast cancer.

PMID- 15487101
TI  - Promotion of physical activity and healthy food choices was hampered by
      competitiveness, lack of quality food, easy access to non-nutritious food, and
      time constraints.

PMID- 15487102
TI  - Good communication with healthcare providers helped patients with multiple
      sclerosis to cope and adapt.

PMID- 15487103
TI  - Patients used the internet to transform their cancer experiences.

PMID- 15487104
TI  - Patients with colorectal cancer expressed a loss of adulthood related to a loss
      of professional and sexual identity, dignity, privacy, independence, and ability
      to socialise.

PMID- 15487105
TI  - Patients with heart failure had inadequate information about the disease and
      lacked the tools for optimal self care.

PMID- 15487106
TI  - Spouses of patients with coronary heart disease had varied perceptions about its
      aetiology and drug treatment.

PMID- 15487107
TI  - Comments on Clinical and economic comparison of epoetin alfa and darbepoetin
      alfa.

PMID- 15487108
TI  - Intrapancreatic true arterial aneurysm mimicking pancreatic tumor.

PMID- 15487109
TI  - [Education in gastroenterology].

PMID- 15487110
TI  - Predictors of prolonged hospital stay following open and laparoscopic gastric
      bypass for morbid obesity: body mass index, length of surgery, sleep apnea,
      asthma, and the metabolic syndrome.
AB  - BACKGROUND: The number of weight reduction operations performed for type II and
      type III obesity is rapidly escalating. Risk of surgery has been infrequently
      stratified for patient subgroups. The purpose of this study was to identify
      patient characteristics that increased the odds of a prolonged hospital length of
      stay (LOS) following open or laparoscopic Roux-en-Y gastric bypass (RYGBP).
      METHODS: The hospital records of 311 patients who underwent RYGBP in a 6-month
      period were retrospectively reviewed. Patient characteristics including the
      presence of significant obesity-related medical conditions were recorded.
      Analysis was based on intent to treat. Univariate and step-wise logistic
      regression analysis was used to identify the odds ratio (OR) and adjusted odds
      ratio (AOR) for predictors of an increased hospital LOS. RESULTS: Datasets for
      311 patients were complete.159 patients underwent open vertical banded gastro
      plasty-Roux-en-Y gastric bypass (VBG-RYGBP) and152 laparoscopic RYGBP (LRYGBP).
      78% of patients were female. Median age was 40 years (range 18-68). Median BMI
      was 49 kg/m2 (range 35-82). 17% of patients had sleep apnea, 18% asthma, 19% type
      2 diabetes, 13% hypercholesterolemia and 44% hypertension. Median length of
      surgery for open VBG-RYGBP (64 minutes) was significantly faster than forLRYGBP
      (105 minutes). Median length of stay was significantly shorter for LRYGBP (2
      days) than openVBG-RYGBP (3 days). Univariate logistic regression analysis
      identified 6 predictors of increased LOS:open surgery (0.4 OR); increasing BMI
      (60 kg/m2 0.38 OR; BMI 70 kg/m2 0.53 OR); increasing length of surgery (120 min
      0.33 OR; 180 min 0.48 OR); sleep apnea (2.25 OR); asthma (3.73 OR); and
      hypercholesterolemia (3.73 OR). Subset analysis identified patients with the
      greatest odds for a prolonged hospital stay: women with asthma (2.47 AOR) or
      coronary artery disease (8.65 AOR); men with sleep apnea (5.54 OR) or the
      metabolic syndrome (6.67-10.20 OR); and patients undergoing a laparoscopic
      operation with sleep apnea (11.53 AOR) or coronary artery disease(12.15 AOR).
      CONCLUSIONS: Open surgery, BMI, length of surgery,sleep apnea, asthma and
      hypercholesterolemia all increased the odds of a prolonged LOS. Patients with the
      greatest odds of long LOS were women with asthma or coronary disease, men with
      sleep apnea or the metabolic syndrome, and patients undergoing laparoscopic
      surgery with sleep apnea or coronary artery disease. Patients at high-risk for
      prolonged hospital stay can be identified before undergoingRYGBP. Surgeons may
      wish to avoid high-risk patients early in their bariatric surgery experience.

PMID- 15487111
TI  - Shortage of head and neck surgeons could threaten treatment.

PMID- 15487120
TI  - The conundrum of cancer: 50 issues of The Lancet Oncology.

PMID- 15487121
TI  - Introduction: The case of Ms. G.

PMID- 15487122
TI  - The challenge of clinical empathy.

PMID- 15487123
TI  - Reading experience: Jodi Halpern's From Detached Concern to Empathy.

PMID- 15487124
TI  - Empathy as epistemological tool: commentary on Jodi Halpern's From Detached
      Concern to Empathy.

PMID- 15487125
TI  - Catastrophic emotions and respect for autonomy.

PMID- 15487126
TI  - Practicing medicine in the real world: challenges to empathy and respect for
      patients.

PMID- 15487127
TI  - Women and anxiety disorders: implications for diagnosis and treatment.
      Proceedings of a conference, November 19-21, 2003, Chantilly, Virginia, USA.
AB  - Community studies indicate that 19% of men and 31% of women will develop some
      type of anxiety disorder during their lifetime. The impact of gender is profound
      in that it increases the likelihood of developing an anxiety disorder by 85% in
      women compared to men. Sex difference in prevalence rates are apparent as early
      as age 6, when girls are twice as likely as boys to have an anxiety disorder. In
      the National Comorbidity Survey, the prevalence rates for panic disorder in women
      and men were 5% and 2%, respectively. Agoraphobia, which often coexists with
      panic disorder, has a lifetime prevalence rate of 7% in women and 3.5% in men.
      Prevalence of trauma is increased in young women as well, and is experienced
      earlier in life; 62% of sexual assaults are inflicted on females < or = 18 years
      of age, and 29% occur in children < 11 years of age. Comorbidity of anxiety in
      women complicates other medical conditions as well. For example, panic disorder
      is highly comorbid with CHD, which remains the leading cause of death in women in
      developed countries. Fluctuations in reproductive hormone levels during the
      female life cycle is thought to be responsible for modulating anxiety. This is
      often implicated in the later age of onset, the more sudden and acute symptom
      emergence, and the more episodic course of OCD in women, and in the high
      prevalence(47.4%) of PMDD. Pregnancy appears to be a protective period for some
      anxiety disorders, including panic, while for others, such as OCD, it may be
      associated with onset. Hormonal changes during pregnancy, such as increased
      prolactin, oxytocin, and cortisol, may contribute to the suppression of stress
      response that occurs during this period. Despite a large and growing body of
      literature on anxiety disorders in general, the available data relating to women
      and girls falls short of informing aspects of diagnosis, treatment, and
      prevention that may entail sex differences. Additional work is required to
      understand the biological and psychosocial causes of these differences.

PMID- 15487128
TI  - [Monkeypox virus infection].

PMID- 15487129
TI  - Radiotherapy in the UK: there are problems--what are the solutions?

PMID- 15487130
TI  - Re-audit of radiotherapy waiting times 2003.
AB  - AIMS: There has been increasing concern, by clinical oncologists in the UK, about
      the continuing long waiting times for radiotherapy treatment. An audit of
      patients starting treatment in 1 week in 2003 was carried out to determine
      waiting times and to compare current results with those obtained from a similar
      audit in 1998. MATERIALS AND METHODS: All centres in the UK completed the audit,
      which recorded waiting-list status and treatment intent for all new treatments
      started in 1 week, date of booking form completion and fractionation scheme used.
      RESULTS: Waiting times have lengthened in most centres for all categories of
      patients although, for palliative treatments, there was no additional increase in
      median waiting time compared with the last audit. Fewer patients in all
      categories are being treated within the Joint Collegiate Council for Oncology
      (JCCO) guidelines. Single-fraction treatments are now common for palliation. Most
      adjuvant treatment uses one of three prescriptions. In each Strategic Health
      Authority (StHA), the same proportion of the total number of patients with cancer
      seemed to be given radiotherapy. There was no obvious simple correlation of
      radiographer, physicist or treatment machine numbers with waiting times.
      CONCLUSION: The results of this survey suggest a continuing mismatch between
      capacity and demand. Increased complexity of radical treatments, and possibly
      more patients being referred for treatment, may have been offset in part by
      reduced fractionation for palliation.

PMID- 15487131
TI  - Cellular immunotherapy for cancer: current concepts and clinical perspectives
      Monitoring immune responses and clinical trials: part II.

PMID- 15487132
TI  - Guidelines on the diagnosis and management of solitary plasmacytoma of bone and
      solitary extramedullary plasmacytoma.

PMID- 15487133
TI  - Lymphoma presenting as a parotid tumour: a population-based study of diagnosis,
      treatment and outcome on behalf of the Scotland and Newcastle Lymphoma Group.
AB  - AIMS: Lymphoma presenting as a parotid tumour is rare. Previous published studies
      have been small and have not characterised fully the nature of lymphoma
      presenting this way. We studied the clinical features, diagnosis, prognosis and
      treatment in a patient group identified from the Scotland and Newcastle Lymphoma
      Registry, which is a prospectively collected population-based register of
      consecutive cases of lymphoma since 1979. MATERIALS AND METHODS: The study
      includes all patients with a biopsy-proven lymphoma in the parotid gland as the
      first presentation of their disease. RESULTS: Of 136 cases identified, 128 had
      non-Hodgkin's lymphoma (representing 1.5% of the 8499 non-Hodgkin's lymphomas in
      the registry) and eight had Hodgkin's disease (0.3% of the 2716 cases
      registered). Female to male ratio was 1.3:1, and median age was 69 years (range
      19-94 years). Fifty-six per cent of patients had stage I, 16% had stage II, 11 %
      had stage III and 17% had stage IV disease. Diagnostic method was recorded in 81
      cases; 47 of these were by parotidectomy. Overall median survival was 90 months,
      with a 5-year survival of 54%, but there was substantial variation according to
      age, grade, stage and International Prognostic Index (IPI). Diagnosis was often
      made by unnecessary major facial surgery, which could be avoided in many cases.
      CONCLUSION: Treatment should be directed by standard practice for lymphoma
      according to stage and histological classification.

PMID- 15487134
TI  - The NICE guidance on supportive and palliative care--implications for oncology
      teams.

PMID- 15487135
TI  - Computed tomographic simulation in palliative radiotherapy: the Princess Margaret
      Hospital experience.
AB  - AIM: To examine the pattern of palliative radiation planning and the use of
      computed tomographic simulation (CTSIM) for this purpose. MATERIALS AND METHODS:
      We reviewed our department's external radiotherapy database for all courses of
      treatment with a palliative intent during the period of April to June 2002.
      Patient characteristics and treatment details were compared based on whether
      CTSIM had been used or not. RESULTS: During the above period, 593 courses of
      external radiation treatment were delivered with palliative intent in our
      department. Of these, 100 treatments (17%) were planned with the help of CTSIM.
      The mean age of patients with CTSIM (62.9 years) was not significantly different
      with the patients planned without CTSIM (63.6 years). CTSIM use varied by
      treatment location, being highest in mediastinum/oesophagus (48%) and
      pancreas/stomach (47%) treatments, and lowest in spine (6%), lung (3%) and long
      bones (4%) (P < 0.01). Only 3% of palliative treatments without CTSIM were
      prescribed using multiple/complex fields (all field arrangements more complex
      than a single field or two opposed parallel fields). Although significantly
      higher (P < 0.001), this proportion was also only 24% in the cases planned with
      CTSIM. Only 12% of treatments without CTSIM were prescribed with more than 5
      fractions, whereas 32% of CT-simulated treatments included more than 5 fractions
      (P < 0.001). CONCLUSION: CTSIM was used much less frequently in our department's
      palliative radiotherapy compared with its use in radical treatments. The
      relatively low rate of multiple/complex fields planned in CT-simulated cases
      suggested that CTSIM was mostly used to improve tumour localisation. The optimal
      role of CTSIM in palliative radiotherapy will most probably evolve, based on an
      enhanced understanding of the implications from improved localisation and optimal
      planning techniques on clinical outcomes, patient convenience and resource
      accessibility.

PMID- 15487136
TI  - Solid cancers after therapeutic radiation--can we predict which patients are most
      at risk?

PMID- 15487137
TI  - Learning in oncology: lessons from the 20th century, learner-centred education
      for the 21st century: part II.

PMID- 15487138
TI  - Survey of the suitability of breast-cancer patients for inclusion into adjuvant
      clinical trials over 11 consecutive weeks in a single new-patient clinic.

PMID- 15487139
TI  - Negotiations of surface: archaeology within the early strata of psychoanalysis.
AB  - Freud's "The Aetiology of Hysteria" (1896) begins with the description of an
      excavation. With this passage as a point of departure, the role of archaeology in
      Freud's early psychoanalytic formulations is examined. The archaeological imagery
      in his later writings and the collection of ancient objects that came to fill his
      consulting room and library are well known, but the passage must be
      contextualized in its own moment to show the influences that led Freud to
      articulate an "expanse of ruins" at this particular time. In the late nineteenth
      century, archaeology provided an innovative representation of "topography"--one
      that exceeded the limitations of this concept in neuroanatomical visualizations
      and that offered the layered site as an analogy for psychic processes.
      Schliemann's highly publicized excavations of Troy are recognized as an important
      but not exclusive source for Freud's narrative of 1896. The additional, perhaps
      dominant, impact of Austrian archaeological projects in the 1880s and 1890s is
      noted. These enjoyed considerable visibility in Vienna, and were used by Freud to
      symbolize the processes of destruction and rebuilding in the city itself. The
      excavation imagery in "Aetiology" is thus posited as the continuation of a
      complexity of meanings that Freud brought early on to his engagement with acts of
      unearthing.

PMID- 15487140
TI  - Success and succession.
AB  - The etymology of the word success and its relationship to succession is
      elucidated. Linkage is made to the consequences of unconscious "legitimate" and
      "illicit" fulfillments in life. This is explored in the writings of Freud and
      others. Emphasis is placed on guilt, a major factor blocking the attainment of
      success. This guilt derives from unconscious parricide, which permeates and
      contaminates themes of succession. How early objects, particularly oedipal ones,
      are "killed off" in the process of gaining autonomy and achievement without
      literally invoking unconscious murder is explored. The retaliatory aspects of
      failure are also addressed. Illustrations employing case material are used to
      highlight these theoretical constructs.

PMID- 15487141
TI  - How can we know what we need to know? Reflections on clinical judgment formation.
AB  - What distinguishes a psychoanalyst from any other psychologically minded,
      empathic human being? This seemingly simple question goes to the heart of our
      profession, the way we see ourselves as competent clinicians. To understand a
      patient's material beyond ordinary empathy--that is, to come to a clinical
      judgment--we need to step out of the dyadic, countertransference situation and
      reflect what we've experienced in reference to our clinical theories. An analytic
      vignette shows how a theoretical background can be used to understand and
      interpret to a patient in a way that is deeply meaningful.

PMID- 15487142
TI  - Psychoanalytic understanding of terrorism and massive social trauma.

PMID- 15487143
TI  - Conducting analysis after September 11: implications for psychoanalytic
      technique.
AB  - The September 11, 2001, terrorist attack on the World Trade Center profoundly
      affected the population of New York City, including analysts and analysands. To
      study the effect of this event on the technique of psychoanalysts conducting
      ongoing analysis during the weeks after 9/11, confidential questionnaires were
      sent to all candidates and faculty at the Columbia University Center for
      Psychoanalytic Training and Research. Respondents indicated that in the days and
      weeks following 9/11 they initiated phone calls to their analysands, asked about
      their analysands' families, gave advice when it was requested, offered
      reassurance, and answered personal questions. They did not initiate physical
      contact, discontinue use of the couch, or give unsolicited advice. These
      responses suggest that these analysts made decisions to alter their technique in
      certain ways in the wake of a catastrophic event shared by the community.

PMID- 15487144
TI  - The role of the analyst in the analytic cure during times of chronic crises.
AB  - The role of the analyst in psychoanalytic treatment during periods of chronic
      crises is illustrated with material from two case studies. The first clinical
      vignette shows an analyst able to stay with fears evoked in the patient by the
      traumatic external reality, even as the analyst tried to explore with the patient
      an inner universe that handled this reality in unique ways. The second case study
      focuses on how the analyst's countertransference during this period of chronic
      crises, which she was experiencing along with the patient, made it difficult for
      her to contain the patient's fears and anxieties, because of the threat to her
      own existence, as well as to her identity as an analyst. In this second case the
      analyst, out of denial of the external situation, focused blindly on the
      patient's internal reality in order to counteract her own sense of passivity and
      helplessness in the confrontation with death and destruction. She clung to
      "classical" analysis by trying to analyze the patient's defenses, work them
      through, etc., thus making so-called analytic interpretations rather than staying
      with the patient's fear, as well as her own, and helping the patient more
      directly. A turning point came with the birth of the analyst's granddaughter;
      fear for the new arrival's safety made the analyst sharply aware that it is
      impossible to ignore external reality, that it must be given a place both in
      everyday life and in analysis. This awareness enabled the analyst to contain the
      patients' fears, which helped him feel more supported and facilitated change.

PMID- 15487145
TI  - Healing after Columbine: reflections of psychoanalytic responders to community
      trauma.
AB  - Following the shootings at Columbine High School on April 20, 1999, the Denver
      Psychoanalytic Society provided both immediate and long-term interventions to
      those closely impacted by the tragedy. In this effort, analytically trained
      volunteers faced many personal challenges and role adjustments. To address these
      issues a reflective study group was formed twenty months after the traumatic
      event. Group discussions revealed a surprising number of residual symptoms from
      secondary trauma, as well as opportunities for shared coping among analysts.
      Little has been written about the very human and subjective responses of analysts
      in such circumstances. These experiences may be helpful to others in today's
      world of terrorism and unexpected violent events.

PMID- 15487146
TI  - Music, mourning, and consolation.
AB  - The attacks of September 11, 2001, prompt a consideration of the role of music in
      mourning and trauma. The intrapsychic functions of music in the mourning process
      are explored, as is music as a unique response to trauma and as a special
      aesthetic expression of a range of affects connected with grief. Also explored is
      the allied notion of consolation, a topic underdeveloped in the analytic
      literature.

PMID- 15487147
TI  - Does psychoanalysis have anything to offer an understanding of terrorism? Panel
      report.

PMID- 15487148
TI  - Psychoanalytic education and the new analyst.

PMID- 15487149
TI  - The impact of graduation from psychoanalytic training.
AB  - To examine candidates' experience of graduation from psychoanalytic training,
      1997-2001 graduates of the Columbia University Center for Psychoanalytic Training
      and Research were sent a confidential questionnaire about their first year after
      analytic training. Of this group, 72 percent (23/32) returned the survey.
      Questions focused on the impact of graduation on time availability, net income,
      professional advancement, and sense of personal and professional autonomy.
      Graduates from analytic training were found to have more income in their first
      postgraduate year, a mean increase of 30,000 dollars, and more available time, a
      mean increase of sixteen hours. Increased earnings came primarily from seeing
      more patients during the time made available with the end of classes. In
      addition, graduates did not terminate their control cases or stop supervision.
      Graduates most valued their sense of professional accomplishment and ability to
      spend more time with their families. Although graduates also experienced relief
      from evaluation pressure, they did not rank this high in importance. For
      candidates, graduation profoundly impacts the structure of professional and
      personal life, but does not mean an end to learning.

PMID- 15487150
TI  - Psychoanalytic practice in the early postgraduate years.
AB  - As a pilot investigation for a longitudinal study of psychoanalytic careers, a
      survey was conducted of analysts who graduated during the last fifteen years from
      the Columbia University Center for Psychoanalytic Training and Research.
      Graduates were asked to describe both their analytic practice and their interest
      in pursuing appointment as training and supervising analysts. The 23-item
      questionnaire was completed by 67 of 102 potential respondents (66%). The study
      identified two subgroups of graduates: those who were not certified and were not
      training analysts (GAs), 78% of the sample, and certified and training analysts
      (CAs, TAs), 22% of the sample. GAs started a mean of 1.4 new analytic cases since
      graduation, as compared to CAs and TAs, who started a mean of 5.4 and 8.3 new
      cases, respectively. CAs and TAs also saw more twice-weekly therapy cases than
      did GAs. Once-weekly therapy was the most commonly practiced treatment for all
      subgroups. Interest in becoming a TA was highest during the first five
      postgraduate years and was lower among non-TAs five to fifteen years after
      graduation. Only one of the CA respondents met current APsaA immersion criteria
      for training analyst appointment.

PMID- 15487151
TI  - Boundaries and postanalytic contacts in institutes.
AB  - The work of a COPE study group on boundaries is presented, with particular focus
      on post-termination contact after the training analysis. Through the use of
      clinical examples evocative and illustrative of the complexity of postanalytic
      contacts and relationships in the training analysis situation, a number of
      dilemmas are identified that former analysts and patients face when they meet as
      colleagues after the training analysis is over. These dilemmas, it is argued,
      have implications for the conduct and effectiveness of the training analysis and
      for the institutional cultures and power relations that evolve within institutes.

PMID- 15487152
TI  - On the patient's right to tell.

PMID- 15487153
TI  - 1-2 month out: setting up office systems.

PMID- 15487154
TI  - EHRs: the Fed's big push. Interview by Ken Terry.

PMID- 15487155
TI  - Doctors and "blogs".

PMID- 15487156
TI  - Disability coverage. A buyer's primer.

PMID- 15487157
TI  - Disability coverage. You may have to fight to collect.

PMID- 15487158
TI  - Why big is out.

PMID- 15487159
TI  - Doc, can you write me a note?

PMID- 15487161
TI  - Keep your billing on target.

PMID- 15487160
TI  - How I pick the doctors I'll sue. A conversation with plaintiffs' attorney Bruce
      Fagel, MD, JD. Interview by Berkeley Rice.

PMID- 15487162
TI  - The risk of on-call prescribing.

PMID- 15487163
TI  - Quit complaining.

PMID- 15487175
TI  - Nursing education--the solution or the problem?

PMID- 15487174
TI  - Nursing people with disabilities: who cares?

PMID- 15487176
TI  - Embracing the art and the science of nursing.

PMID- 15487178
TI  - Researching stroke incidence. Interview by Anne Manchester.

PMID- 15487179
TI  - Developing workplace writing skills for nurses.

PMID- 15487180
TI  - Taking responsibility for children's rights.

PMID- 15487182
TI  - No monkeying around in NZNO's year of fair pay.

PMID- 15487181
TI  - Balancing work and family lives.

PMID- 15487183
TI  - Publishing exposure proves an encouraging experience.

PMID- 15487184
TI  - CTU treats NZNO members as 'second class'.

PMID- 15487185
TI  - Defining the nurse practitioner in New Zealand.

PMID- 15487186
TI  - Separate course for psychiatric nursing needed.

PMID- 15487188
TI  - Moving on with no regrets.

PMID- 15487187
TI  - Pay system should recognise nursing knowledge.

PMID- 15487189
TI  - Trialling smoking cessation drug among Maori.

PMID- 15487190
TI  - Evidence alone is not enough to bring about practice change.

PMID- 15487191
TI  - Assisting families with the process of organ donation.

PMID- 15487192
TI  - Hindsight--isn't it a wonderful thing?

PMID- 15487193
TI  - Just another day's in critical care.

PMID- 15487194
TI  - Time to start work on professional portfolios.

PMID- 15487195
TI  - The power of member activism.

PMID- 15487196
TI  - Symposium highlights nursing research.

PMID- 15487197
TI  - Whose poverty is it anyway.

PMID- 15487198
TI  - Article on a nursing ethical issue proves useful.

PMID- 15487199
TI  - Strong interest in overseas nursing article.

PMID- 15487201
TI  - Our nursing history must be documented.

PMID- 15487200
TI  - Child health post-graduate education is available.

PMID- 15487202
TI  - Gastric reflux support network helps parents.

PMID- 15487203
TI  - Children's views on parental separation sought.

PMID- 15487204
TI  - Working against poverty internationally and at home.

PMID- 15487205
TI  - Filling health gaps in the Wairarapa.

PMID- 15487206
TI  - Defining and delivering core midwifery care.

PMID- 15487207
TI  - Youth, pregnancy and health disadvantage.

PMID- 15487208
TI  - Creating healthy school communities.

PMID- 15487209
TI  - A lifetime of nursing in a rural community. Interview by Teresa O'Connor.

PMID- 15487210
TI  - Proposed employment law needs amendment.

PMID- 15487211
TI  - A diary of distress.

PMID- 15487212
TI  - The challenges of being a negotiating team member.

PMID- 15487213
TI  - Determining new nursing scopes of practice.

PMID- 15487214
TI  - Te Runanga chair shares an 'inside out' experience.

PMID- 15487216
TI  - Addressing the problem of masculinity.

PMID- 15487215
TI  - Profiling Maitera Tutahi.

PMID- 15487220
TI  - Male psychiatric nurses implicated in 'euthanasia'.

PMID- 15487221
TI  - Mental health and acute nursing attract most male nurses.

PMID- 15487224
TI  - Protecting the position of enrolled nurses.

PMID- 15487225
TI  - Male nurses--the struggle for acceptance.

PMID- 15487226
TI  - From segregation to integration--one male nurse's journey. Interview by Teresa
      O'Connor.

PMID- 15487227
TI  - Male student experienced a sense of isolation. Interview by Teresa O'Connor.

PMID- 15487228
TI  - Male nurses are 'always remembered'.

PMID- 15487229
TI  - Discrimination brings advantages.

PMID- 15487230
TI  - Facing up to severe acute respiratory syndrome.

PMID- 15487231
TI  - Mixed-sex rooms--invading patients' privacy?

PMID- 15487232
TI  - Men in nursing--what's their rightful place?

PMID- 15487233
TI  - Guidelines, regulations, standards, policies and....

PMID- 15487234
TI  - Campaigning for a fourth week's leave.

PMID- 15487235
TI  - Fronting up to pay equity issues.

PMID- 15487245
TI  - Why the angst about nurse practitioners?

PMID- 15487240
TI  - First New Zealand-trained male nurse remembered.

PMID- 15487246
TI  - The voice of nurse practitioners...

PMID- 15487247
TI  - Pain management initiatives improve care.

PMID- 15487248
TI  - Supporting nurses to manage patients' pain. Interview by Anne Manchester.

PMID- 15487249
TI  - The challenging field of pain management nursing.

PMID- 15487250
TI  - Making the case for mental health nursing standards.

PMID- 15487251
TI  - Dreaming of nurses' collective strength.

PMID- 15487252
TI  - Changing emergency department practice.

PMID- 15487253
TI  - Assessing pain key to proper treatment.

PMID- 15487254
TI  - The next round in the pay campaign begins.

PMID- 15487255
TI  - Using NZNO's library most effectively.

PMID- 15487256
TI  - Ureteral ectopy in the seminal vesicle associated with cyst formation and renal
      dysplasia: contribution of 3D-MRI.
AB  - A case of a congenital anomaly of the urinary tract in a 25-year-old Caucasian
      male is presented. Preoperative and pathologic findings demonstrated an ectopic
      ureter which terminated in a seminal vesicle cyst. Both structures formed an
      abortive common duct at the bladder base. The ipsilateral kidney was dysplastic.
      Findings on voiding cytourethrography, spiral CT, and MRI are discussed and
      correlated with pathologic findings. The authors suggest that MRI, especially
      with the use of 3D sequences, is the examination of choice in the evaluation of a
      complex congenital urogenital anomaly as presented.

PMID- 15487257
TI  - Adrenal oncocytoma: US and CT findings.
AB  - We describe a case of an oncocytoma occurring in the adrenal gland, a rare
      location, and describe US and CT findings of this tumor in our patient. The mass
      was well marginated but heterogeneous on both CT and US and unfortunately the
      imaging findings of the tumor are non-specific.

PMID- 15487258
TI  - Synovial haemangioma diagnosed during knee arthro-CT.
AB  - Synovial haemangiomas are uncommon lesions most frequently found in the knee. We
      report a case in the popliteal area fortuitously demonstrated during knee msCT
      arthrography in a young female. The diagnosis was made possible by the sharp
      enhancement of the tumor caused by the venous drainage of the contrast medium
      injected into the synovial cavity. The diagnosis was confirmed by msCT
      angiography and MRI.

PMID- 15487259
TI  - Imaging of percutaneous pericardioperitoneal shunt in patient with malignant
      cardiac tamponade.
AB  - Patients with malignant pericardial tamponade have a poorer prognosis than
      patients with non malignant effusion in a neoplastic context. Pericardial
      metastases occur frequently in advanced-stage disease patients, in 5-10% of all
      patients with cancer. Among a personal series of five patients who underwent the
      same procedure, we report characteristic imaging features of a 16-year-old man
      presenting with malignant tamponade, who was successfully treated by percutaneous
      pericardioperitoneal shunt. Percutaneous balloon pericardiotomy is a well
      tolerated, safe, and well-known technique, but little has been described
      concerning imaging the percutaneous pericardioperitoneal shunt. This life-saving
      procedure should be used for recurrence of malignant tamponade and should also be
      considered for initial treatment. Advantages of the percutaneous procedure
      include minimal discomfort, low morbidity rate, and efficiency similar to
      surgical pericardiotomy without sedation.

PMID- 15487260
TI  - Imaging in trauma of the pelvis and hip region.
AB  - Trauma of the pelvis and the hip are frequent and the most common lesions are
      fractures and dislocations. There are other traumatic lesions around the pelvis,
      including epiphysiolysis of the femoral head and apophysiolysis of the common
      muscle insertions around the hip. Cartilaginous lesions and some less frequent
      fractures are also illustrated in this article. We are not claiming to give a
      complete overview of traumatic injuries to the pelvis and the hip, but want to
      illustrate some more and some less frequent lesions.

PMID- 15487261
TI  - Fatal lung destruction due to phthisis.

PMID- 15487262
TI  - Reversible acute abdominal episode of hereditary angioneurotic edema.

PMID- 15487263
TI  - Medicolegal aspects of penetrating hand and foot trauma: ultrasound of soft
      tissue foreign bodies.

PMID- 15487264
TI  - Get with the guidelines to improve heart care.

PMID- 15487265
TI  - Prognosis assessment in patients with decompensated heart failure. Simple
      clinical parameters or neurohormonal factors.

PMID- 15487266
TI  - Female gender, myocardial remodeling and cardiac failure: are women protected
      from increased myocardiocyte apoptosis?
AB  - Heart failure appears to be less common and less severe in females, and elderly
      women have a better overall survival after myocardial infarction than males and
      also a decreased risk of arrhythmic death. Human and animal studies also show
      that females display more favorable cardiac remodeling in several experimental
      and clinical conditions. However, the underlying pathophysiologic mechanisms have
      not been established, even though estrogens, beta-adrenergic stimulation, the
      renin-angiotensin system, and a greater resistance to myocardiocyte apoptosis in
      females have been proposed as hypothetical contributing factors. Indeed,
      epidemiologic, experimental and clinical evidence of gender differences in
      myocardial remodeling and heart failure favoring women could prompt the use of
      female myocardial progenitor or stem cells for cellular replacement therapy in
      cardiac failure, on the premises of a greater protection from myocardial
      apoptosis and unfavorable remodeling in women.

PMID- 15487267
TI  - Regression of left ventricular hypertrophy and cardiovascular risk changes in
      hypertensive patients.
AB  - Hypertensive left ventricular hypertrophy (LVH) may be detected in about one
      third of people with hypertension. When an individual with elevated blood
      pressure develops LVH, the risk of adverse cardiovascular events in the ensuing
      years almost doubles even in the absence of symptoms. Because of this high added
      risk, hypertension and other modifiable risk factors should be managed
      aggressively with lifestyle measures and drugs. LVH can be considered a
      biological assay which reflects and integrates the long-term exposure not only to
      pressure overload, but also to several hemodynamic and non-hemodynamic factors
      which may promote progression and instabilization of atherosclerotic lesions and,
      ultimately, lead to adverse clinical events. LVH can partially or totally regress
      following antihypertensive treatment and lifestyle changes including losing
      excessive weight and decreasing salt intake. Angiotensin II antagonists and ACE
      inhibitors seem to be the most effective drugs for reversing LVH. Evidence is
      accumulating that regression of LVH is associated with a significant reduction in
      the subsequent risk of cardiovascular disease. According to a recent meta
      analysis, effective reversal of LVH is associated with a 59% lesser risk of
      subsequent adverse events as compared with the persistence or new development of
      LVH.

PMID- 15487268
TI  - Comparison of hemodynamics during hyperthermal immersion and exercise testing in
      apparently healthy females aged 50-60 years.
AB  - BACKGROUND: Owing to excessive worries regarding adverse cardiac events,
      hyperthermal balneotherapy for patients with coronary artery disease is
      underprescribed. However, very few cardiac events occur in similar heat stress
      during Finnish sauna bathing. Exercise testing has proven to be a safe diagnostic
      procedure even in survivors of myocardial infarction. METHODS: We compared the
      effects of hyperthermal immersion and exercise testing on cardiac hemodynamics in
      21 apparently healthy women aged 50-60 years. The maximal symptom-limited bicycle
      exercise test was performed according to the modified protocol of Wasserman.
      Hyperthermal immersion was carried out in 40 degrees C water and was completed by
      increasing the core temperature by about 2 degrees C. The left ventricular
      function was evaluated using continuous measurement of thoracic electric
      bioimpedance during both tests. The blood pressure, index of contractility and
      heart rate were measured directly, whereas the cardiac index, left cardiac work
      index and systemic vascular resistance index were calculated. RESULTS: The
      hemodynamic response, as assessed at continuous non-invasive monitoring, showed
      substantial differences between hyperthermal immersion and exercise testing.
      Overall, we found a significantly lower hemodynamic load during hyperthermal
      immersion in comparison with exercise testing. Entering the bath, there was a
      significant decrease in the left cardiac work, contractility and blood pressure.
      We recorded a slight increase in the heart rate towards peak hyperthermal
      immersion. However, other modulators such as the mean arterial pressure, index of
      contractility, cardiac index and left cardiac work index decreased even below
      resting values. CONCLUSIONS: Excessive hyperthermal immersion induced a lower
      hemodynamic load in apparently healthy women than standard maximal exercise
      testing.

PMID- 15487269
TI  - Effects of carvedilol on ventriculo-arterial coupling in patients with heart
      failure.
AB  - BACKGROUND: Ventriculo-arterial coupling, defined as the ratio of the effective
      afterload (Ea) to contractility (Ees), reflects the mechano-energetic performance
      of the heart and is increased in chronic heart failure (CHF); the aim of
      treatment is to reduce its value. We studied the effect of carvedilol on the
      Ea/Ees ratio in patients with CHF treated with ACE-inhibitors, diuretics, and
      digoxin. METHODS: Between November 1999 and October 2001, 36 consecutive
      ambulatory patients (aged 31 to 76 years) with stable CHF and idiopathic or
      hypertensive cardiomyopathy, in sinus rhythm and with a left ventricular ejection
      fraction < or = 40%, were started on carvedilol and the dose was increased to the
      maximum tolerated. Ees was calculated as the left ventricular systolic pressure-
      taken as the systolic arterial pressure measured using the cuff manometer
      simultaneously with two-dimensional echocardiographic recordings--divided by the
      left ventricular end-systolic volume. Ea was measured as the ratio of the left
      ventricular systolic pressure to the stroke volume. All patients were
      investigated prospectively after 6 and 12 months of treatment. RESULTS: Out of 36
      patients, 4 did not tolerate the drug and were dropped out. At 6.35 +/- 1 months,
      the daily dosage of carvedilol was 49.7 +/- 21 mg. The NYHA functional class
      improved from 1.52 +/- 0.67 to 1.29 +/- 0.53 (p = 0.017), the heart rate markedly
      diminished from 73.6 +/- 13.3 to 60.8 +/- 10.8 b/min (p < 0.001) and so did Ea
      (3.35 +/- 0.91 to 2.84 +/- 0.93, p = 0.001). Peripheral resistances and Ees did
      not change. Therefore, the decrease in the Ea/Ees ratio (2.61 +/- 0.78 vs 2.19 +/
      0.89, p = 0.004) and the related increase in left ventricular ejection fraction
      (28.8 +/- 5.68 vs 33.3 +/- 7.5%, p < 0.001) were due to the decrease in Ea, while
      Ees did not vary significantly. Moreover, the Ea reduction was related linearly
      to the decrease in heart rate (r = 0.46, p = 0.001). There was no change in
      diuretic or ACE-inhibitor dosing during carvedilol titration. At 14.7 +/- 2
      months of follow-up, no further variation occurred, short of a trend toward a
      slight increase in Ees (1.38 +/- 0.49 to 1.58 +/- 0.65, p = 0.07). CONCLUSIONS:
      Carvedilol, added to the conventional therapy of CHF, improves left ventricular
      performance and reduces the Ea/Ees ratio by decreasing Ea, mainly through a
      reduction in heart rate. This effect is already evident at 6 months and persists
      later on, while only after 12 months does Ees tend to increase slightly.

PMID- 15487270
TI  - Use of digitalis in the treatment of heart failure: data from the Italian Network
      on Congestive Heart Failure (IN-CHF).
AB  - BACKGROUND: Since the large multicenter DIG trial has shown no effects of
      digitalis on the all-cause mortality of patients with chronic heart failure (HF),
      the broad prescription of this drug in patients with HF appears to be at the very
      least, questionable. The aims of this study were: to analyze prescription
      patterns of digitalis, from 1995 to 2000, in a large group of outpatients with
      HF; to analyze the independent predictors of digitalis prescription and to
      evaluate the impact of the results of the DIG trial on the prescription rate of
      this drug. METHODS: From 1995 to 2000, 11 070 HF outpatients (mean age 64 +/- 12
      years, ejection fraction 35 +/- 12%) were enrolled in a large Italian database.
      RESULTS: Out of 11 070 patients, 7198 (65%) were treated with digitalis. At
      multivariate analysis, the following variables were independently associated with
      digitalis prescription; atrial fibrillation (odds ratio [OR] 3.3, 95% confidence
      interval [CI] 2.9-3.8), ejection fraction < 30% (OR 1.7, 95% CI 1.5-1.9), NYHA
      class III-IV vs II-III (OR 1.3, 95% CI 1.2-1.5), admission for HF during the
      previous year (OR 1.4, 95% CI 1.2-1.5). After the publication of the DIG trial,
      there was a significant reduction in the rate of digitalis prescription: the
      percentage of patients taking digitalis fell from 68% in 1996-1997 to 61% in 1998
      1999 (p < 0.001). CONCLUSIONS: Over 60% of Italian outpatients with HF were
      treated with digitalis; as expected, patients with a low ejection fraction,
      atrial fibrillation and in a more advanced stage of HF are more likely to receive
      this drug. Finally, after the publication of the DIG trial, the rate of digitalis
      prescription significantly decreased.

PMID- 15487271
TI  - Myocardial viability after primary coronary angioplasty: low-dose dobutamine
      stress echocardiography versus myocardial contrast echocardiography.
AB  - BACKGROUND: Successful reperfusion therapy in patients with acute myocardial
      infarction (AMI) improves survival. Indeed, after AMI myocardial dysfunction may
      be reversible (hibernating or stunned myocardium). Low-dose dobutamine stress
      echocardiography (LDDSE) provides us with the possibility of evaluating viable
      myocardial segments, while myocardial contrast echocardiography (MCE) allows the
      study of the microcirculation in the same myocardial areas. The aim of our study
      was to compare LDDSE and MCE, in the prediction of the recovery of segments in
      patients with AMI who were submitted to primary coronary angioplasty (PTCA).
      METHODS: We studied 14 patients with AMI. Both LDDSE and MCE with Levovist were
      performed after primary PTCA. The viability gold standard was a recovery of
      contractility detected at echocardiography 2 months later. RESULTS: For LDDSE,
      the sensitivity was 91%, the specificity 71% and the positive and negative
      predictive values were 93 and 64% respectively. For MCE, the sensitivity was 94%,
      the specificity 44%, the positive predictive value 89%, and the negative
      predictive value 59%. Two tests agreed in 81% of the cases. Stress
      echocardiography and contrast echocardiography agreed in 81% of cases.
      CONCLUSIONS: LDDSE has a very good positive accuracy, it has an acceptable
      negative predictive value and is relatively cheap. On the other hand, MCE has a
      good positive accuracy, but a low negative accuracy and carries a high cost. The
      integration of these two tests, which are too expensive in clinical practice,
      could improve our comprehension of the post-PTCA pathophysiology.

PMID- 15487272
TI  - Early outcome after paclitaxel-eluting stents in patients with acute and subacute
      myocardial infarction. A clinical study.
AB  - BACKGROUND: Paclitaxel-eluting stents (PES) have been proven to prevent in-stent
      restenosis in patients submitted to elective percutaneous coronary intervention.
      No data are so far available about the safety and efficacy of PES in acute and
      subacute myocardial infarction. The aim of the present investigation was to
      evaluate the occurrence of in-hospital adverse events in patients with acute and
      subacute myocardial infarction submitted to PES implantation. METHODS: From June
      1 to July 31, 2003, we implanted 53 PES in 43 consecutive patients with acute (34
      patients) and subacute (9 patients) myocardial infarction. RESULTS: In 65.1% of
      the patients the culprit lesion was located in the left anterior descending
      artery. Direct stenting was performed in 27.9% and glycoprotein IIb/IIIa
      inhibitors were used in 74.4%. Before the procedure a TIMI flow 0-1 was present
      in 46.5% while post-procedural TIMI flow 3 was achieved in all patients. A pre
      procedural TIMI thrombus grade 2 to 5 was present in 67.8%. No death,
      reinfarction, early post-infarction angina or any other episode referable to in
      stent thrombosis were observed during hospitalization. No patient was submitted
      to target lesion revascularization. At short-term follow-up with a mean duration
      of 118 +/- 75 days from discharge no cardiac or noncardiac death, reinfarction or
      any other major adverse coronary events were reported in the study population and
      no target lesion revascularization was performed. CONCLUSIONS: In this study, PES
      implant in patients with acute and subacute myocardial infarction was safe, with
      an early outcome comparable to conventional standard stents and no adverse events
      related to acute or subacute thrombosis.

PMID- 15487273
TI  - Ten-year experience with cryopreserved aortic allografts in the surgical
      treatment of aortic valve pathologies.
AB  - BACKGROUND: The aim of this study was to evaluate the performance of
      cryopreserved aortic allografts (CAA) in the treatment of adult aortic valve
      pathologies. METHODS: Between May 1992 and October 2002, 122 CAA were implanted
      in 119 adult patients with pathologies of the aortic valve. The mean age of the
      patients was 38.03 +/- 13.6 years (range 17-78 years). Thirty had had previous
      cardiac surgery. The principal indication was endocarditis (n = 45). In 66
      patients one or more associated pathologies were present including: an abscess of
      the left ventricular outflow tract (n = 32), an aneurysm of the ascending aorta
      (n = 22), mitral incompetence (n = 10), and coronary artery disease (n = 3). The
      indications for surgery were elective in 77 cases and urgent in 45. The CAA was
      implanted as a total root replacement in 46 patients and as a free-hand in 76. In
      66 patients an associated procedure such as a left ventricular outflow tract
      reconstruction (in 27 cases) was performed. RESULTS: The in-hospital mortality
      was 5.73% (7/122). In one patient the CAA was replaced before discharge with
      another CAA because of a mediastinitis with endocarditis by Candida albicans. At
      the follow-up of the 114 patients discharged from the hospital (mean 50.11
      months, range 1-126 months), 6 patients died and 6 were reoperated. The actuarial
      10-year survival, reoperation-free, endocarditis-free, structural degeneration
      free rates were respectively 83.88, 81.70, 86.30, and 92.80%. CONCLUSIONS: From
      our experience we conclude that CAA are good substitutes for aortic valve
      replacement and even in desperate situations exhibit an acceptable long-term
      performance.

PMID- 15487274
TI  - A uncommon cause of angina during upper limb exercise.
AB  - Subclavian artery stenosis or occlusion may be a cause of myocardial ischemia in
      patients treated using an internal mammary artery graft. Subclavian stenosis may
      cause myocardial ischemia during arm exercise by a coronary-subclavian steal
      phenomenon, with flow inversion in the graft from the coronary tree to the left
      subclavian artery. We here describe a case of a patient developing left
      subclavian occlusion after coronary artery bypass grafting with the left internal
      mammary artery. The lesion was successfully treated with a carotid-subclavian
      bypass. The article underscores the importance of an early diagnosis (possibly
      before bypass surgery) and discusses possible treatments. Percutaneous
      interventions with stent implantation appear the treatment of choice, but surgery
      has an important role in case of total occlusion.

PMID- 15487275
TI  - Myocardial ischemia due to a coronary-pulmonary fistula treated with coil
      embolization.
AB  - We describe one case of myocardial ischemia due to a coronary-pulmonary fistula,
      successfully treated with coils. Coronary fistulae are a rare cause of angina in
      adults with normal coronary arteries. Percutaneous treatment represents an
      alternative to surgery and may be offered as a relatively low risk procedure. The
      choice between surgical and percutaneous treatment must take into account
      clinical and anatomical considerations.

PMID- 15487276
TI  - "Torsade de pointes" in a patient with variant angina.
AB  - Ventricular tachyarrhythmias have been well documented in patients with variant
      angina. Episodes of torsade de pointes have been described infrequently. We
      report a case of a 60-year-old male with a previous history of one vessel artery
      disease and a successful coronary angioplasty with stenting of the left anterior
      descending artery, who experienced an episode of angina at rest and
      electrocardiographic evidence of self-terminating torsade de pointes. After a
      negative coronary angiography and a positive hyperventilation test, the diagnosis
      of variant angina was considered and beta-blockers discontinued and calcium
      channel antagonists prescribed. No other episodes of angina were documented
      during the following 6 months of follow-up.

PMID- 15487277
TI  - Biventricular implantable cardiac defibrillator in dextrocardia with situs
      viscerum inversus.
AB  - A case of dextrocardia in situs viscerum inversus, prior myocardial infarction,
      dilated cardiomyopathy with severe left ventricular systolic dysfunction,
      ventricular tachyarrhythmias and recurrent episodes of heart failure is
      described. Coronary artery bypass grafting for multivessel coronary artery
      disease had been previously performed; coronary and graft anatomy evaluation
      excluded the possibility of any further revascularization procedure.
      Electrocardiography showed left bundle branch block and echocardiography revealed
      significant interventricular mechanical dyssynchrony. After a complete vascular
      and cardiac anatomy evaluation, the patient was submitted to biventricular
      cardiac defibrillator implantation via a right approach and using conventional
      fluoroscopic equipment.

PMID- 15487278
TI  - Spontaneous coronary dissection during postpartum: etiology and controversies in
      management.
AB  - A 31-year-old female with a history of toxic oil syndrome in childhood, presented
      with spontaneous left main coronary dissection 4 weeks after an uncomplicated
      delivery. She had an extensive myocardial infarction, severe left ventricular
      dysfunction and cardiogenic shock which did not resolve following urgent surgical
      revascularization. Temporary left ventricular support and heart transplantation
      were necessary. We analyze the etiology and treatment sequence in what to our
      knowledge is the first case with these characteristics to be reported.

PMID- 15487279
TI  - Non-bacterial endocarditis as first evidence of systemic lupus erythematosus.

PMID- 15487280
TI  - Sutter Health uses advertorials to address complex issues.
AB  - Sutter Health, Pasadena, Calif., is unique in its response to the unprecedented
      attention healthcare is receiving in the news media. Instead of addressing the
      issues in its annual report for a limited audience, or responding defensively to
      media queries, Sutter uses advertorials to tell its own story the way it wants it
      to be understood.

PMID- 15487281
TI  - Press kit kicks off new branding.
AB  - A smartly produced press kit resulted in unprecedented news coverage when
      Denver's Porter Adventist Hospital recently unveiled plans for an extensive 80
      million dollars redevelopment. A news conference was held to announce this plan,
      along with the opening of the hospital's new emergency department. The overall
      effort is part of the new branding strategy of the 75-year-old hospital.

PMID- 15487282
TI  - Roll-out of new logo requires time: North Shore-Long Island Jewish graphically
      integrates its entities.
AB  - North Shore-Long Island Jewish Health System, Great Neck, N.Y., has a new logo,
      designed to create a stronger visual integration among its 17 hospitals and many
      other facilities. It will take about two years to complete the change to the new
      logo because of the complexity and size of the system--it is the eighth largest
      employer in New York City.

PMID- 15487283
TI  - Joint marketing cites excellence: Fairview-University Medical Center advertises
      cooperatively with University of Minnesota Physicians.
AB  - Fairview-University Medical Center and University of Minnesota Physicians, both
      in Minneapolis, are enjoying the benefits of a co-branded advertising campaign.
      It includes print ads, brochures, and other marketing devices.

PMID- 15487284
TI  - Sun Health uses seafaring theme effectively in report to community.
AB  - A seafaring theme seems unusual for a system based in Sun City, Ariz., but Sun
      Health uses it to good advantage in its 2002 Report to the Community. The title,
      Stay the Course, refers to the fact the system plans to stay afloat after four
      consecutive years of operational losses. Now completing its 15th year, Sun Health
      tells readers how it hopes to navigate around the reefs and find clear waters.

PMID- 15487285
TI  - Virginia Hospital Center web site filled with relevant information.
AB  - The web site of Virginia Hospital Center, Arlington, Va., provides a preview of
      the facility's 150 million dollars hospital grand opening along with a wide range
      of healthcare conditions and services.

PMID- 15487286
TI  - Segmental and kinetic contributions in vertical jumps performed with and without
      an arm swing.
AB  - To determine the contributions of the motions of the body segments to the
      vertical ground reaction force (Fz), the joint torques produced by the leg
      muscles, and the time course of vertical velocity generation during a vertical
      jump, 15 men were videotaped performing countermovement vertical jumps from a
      force plate with and without an arm swing. Linear kinematic, Fz, and joint torque
      data were computed and compared using repeated measures analysis of variance.
      Maximum jump height was significantly larger in the arm swing jumps compared to
      the no arm swing jumps and was due to both a higher height of the center of mass
      (CM) at takeoff (54%) and a larger vertical velocity of the CM at takeoff (46%).
      The net vertical impulse created during the propulsive phase of the arm swing
      jumps was greater due to a trend of an increased duration (0.021 s) of the
      propulsive phase and not to larger average values of Fz. In the arm swing jumps,
      the arm motion resulted in the arms making a larger maximal contribution to Fz
      during the middle of the propulsive phase and decreased the negative contribution
      of the trunk-head and thigh to Fz late in the propulsive phase. Last, the arm
      swing decreased the extensor torques at the hip (13%), knee (10%), and ankle
      (10%) early in the propulsive phase but augmented these same extensor torques
      later in the propulsive phase.

PMID- 15487287
TI  - American adults' knowledge of exercise recommendations.
AB  - Physical inactivity is a major risk factor for cardiovascular disease, stroke,
      hypertension, diabetes, obesity, osteoporosis, and some cancers. Approximately
      950,000 Americans die annually from cardiovascular diseases. The purpose of this
      study was to determine whether American adults know which traditional and
      lifestyle physical activities affect health and how they should be physically
      active to achieve a health benefit. Secondary purposes were to determine whether
      this knowledge is a function of gender, ethnicity, education, or age and if those
      who are sufficiently active for a health benefit possess different knowledge
      levels than those not sufficiently active for a health benefit. Items based on
      the Centers for Disease Control and Prevention/American College of Sports
      Medicine principles included knowledge of exercise guidelines and traditional and
      lifestyle physical activities. This information was obtained from 20 questions
      that were part of a national random telephone survey of 2,002 American households
      in the 48 contiguous states and the District of Columbia. Respondents were most
      aware of traditional physical activities (M = 94%) that provide a health benefit
      and less aware of specific exercise guidelines (M = 68%) and lifestyle physical
      activities (M = 71%) that can result in a health benefit. Knowledge was not
      related to physical activity behavior sufficient for a health benefit and only
      slightly related to ethnicity, education, and age. These data suggest that
      physical activity knowledge alone is not sufficient to elicit a behavior;
      however, it provides educators with an understanding of the public's physical
      activity knowledge that could be helpful in developing health promotion and
      physical activity interventions.

PMID- 15487288
TI  - Relationships between body composition and fundamental movement skills among
      children and adolescents.
AB  - The purpose of this study was to examine associations of fundamental movement
      skills (FMS) with measures of body composition among children and adolescents.
      Secondary analyses of cross-sectional data collected from 4,363 children and
      adolescents in Grades 4, 6, 8, and 10 as part of the 1997 New South Wales Schools
      Fitness and Physical Activity Survey were conducted. Six FMS (run, vertical jump,
      throw, catch, kick, and strike) were assessed by observation. Height and weight
      (used to calculate body mass index; BMI) and waist circumference were directly
      measured. Results indicated that the children's and adolescents' ability to
      perform FMS was significantly related to BMI and waist circumference.
      Specifically, BMI and waist circumference were significant predictors for FMS in
      six of the eight demographic groups. Adjusted odds ratios revealed that
      overweight boys and girls in all grades were less likely to possess high levels
      of FMS and more likely to possess low levels of FMS than those who weren't
      overweight. When FMS were partitioned into locomotor and object-control skills,
      nonoverweight boys and girls in each grade were two to three times more likely to
      possess more advanced locomotor skills than overweight boys and girls. However,
      for object-control skills, the only demographic groups in which nonoverweight
      students possessed a greater number of advanced skills than overweight students
      were boys in Grades 6 and 10. There appear to be significant and important
      associations between performance of locomotor skills and weight status among
      children and adolescents. This would suggest that intervention strategies to
      prevent unhealthy weight gain among children and youth might usefully include
      increasing proficiency of locomotor skills as a key component.

PMID- 15487289
TI  - Comparison of anthropometry to dual energy X-ray absorptiometry: a new prediction
      equation for women.
AB  - The purpose of this study was to assess the accuracy of three recommended
      anthropometric equations for women and then develop an updated prediction
      equation using dual energy x-ray absorptiometry (DXA). The percentage of body fat
      (%BF) by anthropometry was significantly correlated (r = .896-.929; p < .01) with
      DXA, but each equation underestimated %BF (3.2-5.6 %BF; p < .01). The following
      DXA criterion (DC) equation was created: %BF= -6.40665 + 0.41946(S3SF) -
      0.00126(S3SF)2 + 0.12515(hip) + 0.06473 (age); (S3SF = sum of triceps,
      suprailiac, thigh; hip = circumference in cm; age = years). The predicted
      residual sum of squares (PRESS) R2 was high (0.86), and the PRESS standard error
      of estimate (SEE) was low (2.5 %BF) for our sample of 150 women. The DC equation
      was further crosschecked on a separate sample of women (n = 25) and again showed
      excellent agreement. The DC equation appears to be a more accurate estimation of
      %BF in women.

PMID- 15487290
TI  - Factorial validity and invariance of a self-report measure of physical activity
      among adolescent girls.
AB  - We examined the factorial validity and factorial invariance of the 3-day physical
      activity recall (3DPAR) using confirmatory factor analysis. Adolescent girls from
      two cohorts (N = 955, N = 1,797) completed the 3DPAR in the eighth grade;
      participants in Cohort 2 (N = 1,658) completed the 3DPAR again 1 year later in
      the ninth grade. The 3DPAR was best represented by two uncorrelated factors in
      Cohort 1. The two-factor, uncorrelated measurement model exhibited evidence of
      cross-validity between Cohorts 1 and 2. This model also exhibited configural and
      partial metric invariance between race and across time. Hence, the 3DPAR
      consisted of two uncorrelated factors underlying three indicators of both
      moderate and vigorous physical activity in this sample of Black and White girls
      across a 1-year period. The 3DPAR can be used in cross-sectional, prospective
      cohort and intervention studies that examine mediators and moderators of physical
      activity among Black and White adolescent girls.

PMID- 15487291
TI  - High school students' physical education conceptual knowledge.
AB  - The value of conceptual physical education knowledge has long been acknowledged
      (American Alliance for Health, Physical Education, and Recreation, 1969; Kneer,
      1981; NASPE, 1995) yet has not been formally measured or assessed. Seven multiple
      choice tests with established validity and reliability (Ayers, 2001b) were used
      to assess the concepts identified in Mohnsen's text (1998). Tests were
      administered to 3,263 high school students at the schools of 17 NASPE Teachers of
      the Year in 16 states. On all tests, girls outscored boys, and Caucasians
      outscored all other racial groups. Examinees' average performance on each test
      was: motor development (65%), exercise physiology (62%), social psychology (60%),
      biomechanics (57%), aesthetic experiences (56%), motor learning (53%), and
      historical perspectives (49%). Analyses of each area determined concepts students
      knew and did not know.

PMID- 15487292
TI  - Self-efficacy theory and the theory of planned behavior: teaching physically
      active physical education classes.
AB  - The purpose of our investigation was to examine determinants of teachers'
      intentions to teach physically active physical education classes (i.e., spend at
      least 50% of class time with the students engaged in moderate to vigorous
      physical activity). Based on the theory of planned behavior, a model was examined
      hypothesizing that teachers' intentions were determined by subjective norm,
      attitude, and perceived behavioral control. Grounded in self-efficacy theory, it
      was hypothesized that program goal importance and hierarchical and barrier self
      efficacy would also predict intention. Using a series of hierarchical regression
      analyses, the theory of planned behavior was supported by accounting for 59% of
      the variance in intention due to attitude, perceived behavioral control, and
      subjective norm. Self-efficacy theory based variables received minimal support.

PMID- 15487293
TI  - Ice can look like glass: a phenomenological investigation of movement meaning in
      one fifth-grade class during a creative dance unit.
AB  - The movement meanings of students (n = 19) in one fifth-grade class during a
      creative dance unit focusing on effort (force, time, space, flow) are
      investigated using a perspective grounded in transcendental phenomenology
      (Husserl, 1931). Data were collected via videotape, journal, and homework
      documents and semistructured interviews. Analytical induction (Patton, 2002)
      structured a four-step analysis process that reduced meaning to its essential
      essence. Movement meaning was found to be a multifaceted construct that varied
      among students within and across five dimensions. To enhance meaningful learning,
      educators are encouraged to consider reflexively (a) their philosophical
      orientation relative to knowledge making and curriculum values, (b) instructional
      techniques that help students' access meaning, and (c) the contribution of dance
      as a source of meaning.

PMID- 15487294
TI  - A longitudinal perspective of the relationship between perceived motivational
      climate, goal orientations, and strategy use.
AB  - Achievement goal theory suggests that goal orientations and the perceived
      motivational climate may influence one another and other motivational variables
      over time. Therefore, the purpose of this study was threefold: (a) to examine the
      relationship between perceived motivational climate and goal orientations over
      time (b) to investigate how goal orientations may fluctuate when the climate was
      in opposition to the initial goal orientation, (c) to determine how the climate
      may impact practice strategies. A set of inventories was administered to 162
      college students at preselected times throughout several 16-week physical
      activity classes. Changes occurred in students' goal orientations, particularly
      when the perceived motivational climate was in opposition to their goal
      orientation. Aspects of the task-involving climate positively predicted practice
      strategies.

PMID- 15487295
TI  - Individual differences of action orientation for risktaking in sports.
AB  - The goal of this article is to explain empirical risk-taking behavior in sports
      from an individual cognitive modeling perspective. A basketball task was used in
      which participants viewed four video options that varied in the degree of
      associated risk. The participants were independently classified by scores on the
      Questionnaire for Assessing Prospective Action Orientation and State Orientation
      in Success, Failure, and Planning Situations as action-oriented or state-oriented
      decision makers. The results of the experiment show that action-oriented players
      shoot faster and more often to the basket and that state-oriented players prefer
      to pass to a playmaker more often. Four versions of a computational model of
      decision making, Decision Field Theory, were compared to evaluate whether
      behavioral differences depend on the focus of attention, the initial preferences,
      threshold values, or an approach-avoidance interpretation of the task. Different
      starting preferences explained individual choices and decision times most
      accurately. Risk taking in basketball shooting behavior can be best explained by
      different preferences for starting values for risky and safe options caused by
      different levels of action orientation.

PMID- 15487296
TI  - Cross-validation of the YMCA submaximal cycle ergometer test to predict VO2max.

PMID- 15487297
TI  - Hospital restructuring in Ontario: lessons learned and next steps.

PMID- 15487298
TI  - "Let's get real". Destroying-restoring community in nursing.

PMID- 15487299
TI  - Family-centered care in Ontario general hospitals: the views of pediatric nurses.
AB  - Registered nurses and registered practical nurses working on pediatric units in
      35 Ontario general hospitals participated in a study that examined their
      perceptions and practices of family-centered care (FCC). The Family-Centered Care
      Questionnaire-Revised (FCCQ-R) was used to collect the data. The participants
      were asked to rate their level of agreement regarding necessary elements
      (perceptions) of family-centered care and whether these elements are part of
      their current work (practice). The participants had a reasonable knowledge of the
      necessary elements of family-centered care, but were not consistently including
      these in their every day work. A number of barriers to the implementation of
      family-centered care were also identified. Perception and practice scores were
      higher among those who had participated in continuing education on family
      centered care than those who had not. The findings suggest that some nurses may
      be having difficulties shifting from a medical helping model of care to an
      enabling helping model of care, which is considered the foundation of family
      centered care. Difficulties in implementing family-centered care appear to be
      systemic, both at the unit and organizational level. Based on the findings,
      implications for practice, education and research are suggested.

PMID- 15487300
TI  - Process evaluation of an integrated model of discharge planning.
AB  - In this study, a new, empirically-derived model of discharge planning for acutely
      ill elderly was evaluated to determine (a) whether it could be implemented in a
      hospital setting, and (b) what facilitated or challenged the implementation. The
      process evaluation involved four case studies conducted on three in-patient units
      of two acute-care hospitals. Data were analyzed using explanation-building and
      case comparison methods. Three main study results emerged: (a) The integrated
      model had the potential to be implemented in a hospital setting when certain
      conditions were in place, (b) use of the integrated approach to discharge
      planning contributed to patient satisfaction, and (c) the materials developed as
      part of the discharge planning protocol required only minor formatting
      modifications in order to be rendered user-friendly. In this article,
      recommendations are made that will facilitate the model's implementation and
      utilization in other clinical settings and ongoing and future process
      evaluations.

PMID- 15487301
TI  - Profile of a leader: Labour relations pioneer: Alice Lillian Wright (1894 -
      2000).
AB  - Alice Wright, who died in March 2000 at age 105 years, was one of Canadian
      nursing's pioneers in labor relations for nurses. The Registrar and Executive
      Director of the Registered Nurses Association of B.C. from 1943 to 1960, she was
      named an Honorary Member of the Canadian Nurses Association in 1962, just one of
      the honors for her pioneering labor relations work, her contributions to
      improvements in standards of nursing education, and her many professional
      contributions nationally and internationally.

PMID- 15487302
TI  - Perspective: Economically speaking about nurse staffing.
AB  - Evidence exists telling us that we are currently in the early stages of a nursing
      shortage, and at the same time consumer demands for health care continues to
      increase. Principals of economics, when applied to such a state forewarn of
      changing times and can help us to predict a future very different that what we
      now see.

PMID- 15487303
TI  - Age-related cognitive slowing: the role of spontaneous tempo and processing
      speed.
AB  - This research studied the relationships between two types of slowing observed in
      aging-loss of general processing speed and slowing of spontaneous tempo-in an
      attempt to test the assumption that there is an internal timing mechanism
      responsible for cognitive age-related decrease. Processing speed has been
      evaluated as a mediator of the relationship between age and working memory,
      concurrently with spontaneous tempo measures. The authors compared the
      performance of young and older adults on tasks involving spontaneous motor tempo,
      processing speed, and working memory. The findings confirmed the agerelated
      slowing of spontaneous motor tempo but did not indicate superiority of tempo
      mediation in the decline in working memory. Processing speed appeared to be a
      major mediator of working memory, but also of spontaneous tempo slowing.

PMID- 15487304
TI  - Attention resources and visible speech encoding in older and younger adults.
AB  - Two experiments investigated adult age differences in the distribution of
      attention across a speaker's face during auditory-visual language processing.
      Dots were superimposed on the faces of speakers for 17-ms presentations, and
      participants reported the spatial locations of the dots. In Experiment 1, older
      adults showed relatively better detection performance at the mouth area than the
      eye area compared to younger adults. In Experiment 2, in the absence of audible
      language, both age groups did not differentially focus on the mouth area. The
      results are interpreted in light of Massaro's (1998, Perceiving talking faces:
      From speech perception to a behavioral principle. Cambridge, MA: MIT Press)
      theoretical framework for understanding auditory-visual speech perception. It is
      claimed that older adults' greater reliance on visible speech is due to a
      reallocation of resources away from the eyes and toward the mouth area of the
      face.

PMID- 15487305
TI  - Age and medication acceptance.
AB  - Patients' willingness to take a newly prescribed medication is an important, but
      little studied, part of the medication process. The authors studied the impact of
      patient age on the perceived importance and interaction of three factors known to
      influence young people: severity of their medical condition, extent of possible
      medication side effects, and level of trust in their physician. A convenience
      sample of 170 French adults aged 18 to 93 rated their likelihood of taking a
      medication intended to alleviate physical suffering in 27 scenarios in which
      three levels (low, moderate, and high) of each of the above three factors were
      combined in an orthogonal factorial design. Among younger participants, high
      trust in the physician was not considered a sufficient reason for high acceptance
      of a new medication; it had to be accompanied by low side effects. Among very
      elderly participants, high trust led to high acceptance almost irrespective of
      the severity of possible side effects. Among the middle aged, trust and side
      effects had largely independent effects. To promote patients' acceptance of newly
      prescribed medications, physicians need to establish trust, but not abuse its
      power in elderly patients.

PMID- 15487306
TI  - Elderly nursing home and day care participants are less likely than young adults
      to approach imbalance during voluntary forward reaching.
AB  - The goal of this study was to determine whether differences exist between young
      and elderly adults in cautiousness or tendency to approach imbalance during a
      forward reaching task. Young (n = 26) and elderly (n = 25) adults participated in
      trials that required them to reach forward as quickly as possible to contact a
      target that moved back and forth, in and out of reach. "Voluntary reach" was
      calculated as the 75th percentile in reach distance over 20 trials. Measures were
      also acquired separately of "maximum attainable reach." Voluntary reach averaged
      53% smaller in elderly than young subjects. This was due to differences in
      maximum attainable reach, and to increased cautiousness among elderly in
      approaching maximum attainable reach (voluntary reach averaged 65% +/- 23% of
      maximum attainable reach in elderly, and 95% +/- 5% in young; p < .001). Thus,
      cautiousness in approaching imbalance reduces voluntary reach in elderly but not
      young subjects. Furthermore, physical capacity (as measured by maximum attainable
      reach) and capacity utilization (as measured by voluntary reach) are independent
      predictors of reaching behavior among nursing home elderly.

PMID- 15487307
TI  - Test-retest reliability of Yale Physical Activity Survey among older Mexican
      American adults: a pilot investigation.
AB  - The objective of the work reported in this paper is to assess test-retest
      reliability of Yale Physical Activity Survey Total Time, Estimated Energy
      Expenditure, Activity Dimension Indices, and Activities Check-list in older
      Mexican American men and women. A convenience-based healthy sample of 49 (42
      women and 7 men) older Mexican American adults recruited from senior recreation
      centers aged 68 to 80 years volunteered to participate in this pilot study. Forty
      nine older Mexican American adults filled out the Yale Physical Activity Survey
      for this study. Fifteen (12 women and 3 men) of the 49 volunteers responded twice
      to the Yale Physical Activity Survey after a 2-week period, and helped assess the
      test-retest reliability of the Yale Physical Activity Survey. Results indicate
      that based on a 2-week test-retest administration, the Yale Physical Activity
      Survey was found to have moderate (rhoI= .424, p < .05) to good reliability (rs =
      .789, p < .01) for physical activity assessment in older Mexican American adults
      who responded.

PMID- 15487308
TI  - Voices from the trenches: nurses' experiences of hospital restructuring in
      Ontario.
AB  - Nurses, the largest occupational group in health care, have been
      disproportionately affected by health care restructuring initiatives. A survey of
      registered nurses in Ontario was conducted in the fall of 1998 to examine factors
      influencing their work life quality in hospital settings. As a part of this
      survey, respondents were provided with an opportunity to share their concerns
      about work conditions in an open ended section of the questionnaire. Almost sixty
      percent of the nurses chose to respond to the open ended question (n = 230),
      divided equally between males and females. The purpose of the qualitative
      component of the study was to obtain a more in depth analysis of the effects of
      hospital restructuring initiatives on staff nurses' working conditions. All
      geographic areas of the province were represented in the responses. A content
      analysis of the data was conducted to determine major themes. Similar themes were
      found across all geographic areas. The four major categories of concerns that
      emerged from the qualitative analysis were quality of worklife, quality of
      patient care, relations with management, and cumulative impact of work conditions
      on feelings and attitudes. Nurses' perceptions of their quality of work life,
      concern for the quality of patient care and their emotional and attitudinal
      responses were very similar to those reported in a recent study of hospital staff
      nurses in the United States. The decade of the 1990's has been characterized as
      one of constant change bordering on chaos within the health care system in Canada
      and the United States. In Canada, government fiscal policies have resulted in
      less money being directed toward health care forcing the system to reorganize in
      order to meet new financial realities. Many of the organizing efforts have been
      directed toward the acute care sector of the health care system. Nurses, as the
      largest occupational group within the health care system, have been
      disproportionately affected by these efforts. The purpose of this study was to
      tap nurses concerns about the effects of these changes on their personal and work
      experiences.

PMID- 15487309
TI  - Healthcare restructuring: the impact of job change.
AB  - Restructuring, particularly redeployment and job change, had a dramatic impact on
      the working conditions and practices of nursing personnel. This study was
      conducted to determine whether nurses (RNs and RPNs) who experienced job change
      perceived their work-lives differently than those who did not undergo job change
      and, whether nurses who experienced different types of job change (new role, new
      unit, or new hospital) varied in their perceptions. A questionnaire exploring
      themes relevant to redeployment was administered to all nurses (N = 3,408) in two
      large teaching hospitals that had undergone restructuring. The response rate was
      50.7% (n = 1,728). Of the responses, 1,662 were used in the analysis. T-tests and
      ANOVAs were used to compare groups of nurses. Nurses who changed their jobs
      perceived their commitment to the organization, their work environment and
      quality of care differently than those who did not change jobs. Nurses with
      different types of job change differed in their organizational commitment,
      perceptions of work-related injuries, attitudes towards job change, need for
      orientation and new knowledge, and feelings about the health care team. Results
      will assist managers to address the specific needs of nurses with different
      experiences of job change in the restructured workplace.

PMID- 15487310
TI  - Restructuring stressors and perceived hospital effectiveness.
AB  - This study examined the relationship of hospital restructuring and downsizing
      stressors with nursing staff perceptions of hospital effectiveness. The data were
      obtained in late 1999 from 744 nurses using questionnaires. The findings
      indicated many significant and independent relationships between restructuring
      and downsizing stressors and perceptions of hospital effectiveness; in all cases,
      nursing staff reporting higher levels of restructuring and downsizing stressors
      also indicated reduced hospital effectiveness. Workload and the effects of staff
      bumping in delivery of patient care were particularly problematic in this regard.

PMID- 15487311
TI  - Discovery Path: a retention strategy for mid-career nurses.
AB  - As health care administrators, policymakers, nursing organizations, and nurses
      begin to deal with the reality of a looming (and to an increasing extent,
      existing) serious shortage of nurses both in Canada and globally, recruitment and
      retention issues are again in the news. Much attention has been directed towards
      two responses: (a) attracting young people into the profession and helping them
      integrate into and identify with nursing as a lifelong career, and (b) developing
      sustainable retention strategies to ensure that nurses remain in nursing. One
      population that requires particular attention is the mid-career group of nurses.
      Those nurses, in their late 30s and 40s with 15 and more years of experience,
      have the professional memory that employers count on, the expertise that patients
      and clients require, and the experience and wisdom that young nurses depend on
      for coaching, mentoring, and support. Retention strategies targeted to these mid
      career nurses require a diverse set of activities that are focused on those
      nurses' specific stage of personal and professional development and that
      recognize their unique needs. The purpose of this article is to describe a
      program that targets mid-career nurses, predominantly women who, having spent
      much of their careers and lives caring for others-children, parents, patients-are
      beginning to question their own futures. The goals of the program and the
      experiences of one group of nurses in the program, as well as the results of a
      two-year follow up with them, will be discussed. Recommendations for future
      retention strategies will also be offered.

PMID- 15487312
TI  - Profile of a leader. Katherine E. MacLaggan: New Brunswick's nurse revolutionist
      with evolutionary strategies.

PMID- 15487313
TI  - Cytotoxic substances from Aspergillus fumigatus in oxygenated or poorly
      oxygenated environment.
AB  - Aspergillus fumigatus often causes serious health problems. The airway of the
      human body, the most common initial site of damage, is always exposed to an
      oxygenated condition, and the oxygen concentration may play a critical role in
      the virulence of A. fumigatus. In this study, oxygen content, fungal growth, the
      production of cytotoxic substance(s) in the fungal culture, and their
      relationship were investigated. Two clinical strains of A. fumigatus were
      cultured under certain oxygen contents (10, 14 and 20%), and cytotoxicity of
      their culture filtrates on murine macrophages and their fungal growth were
      evaluated. The components of these filtrates were analyzed by gas chromatography
      mass spectrometry. All culture filtrates contained gliotoxin and showed potent
      cytotoxicity on macrophages at very low concentration. The amount of gliotoxin in
      the culture filtrate prepared at 10% oxygen was markedly less, but diminutions in
      fungal growth and cytotoxicity of this culture filtrate were negligible. These
      results suggest that a well-oxygenated condition is suitable for the production
      of gliotoxin by A. fumigatus. A significant role of cytotoxic substances(s) other
      than gliotoxin is also suggested.

PMID- 15487314
TI  - Enhancement of amphotericin B activity against Candida albicans by superoxide
      radical.
AB  - This study aimed to examine the involvement of oxidative damage in amphotericin B
      (AmB) activity against Candida albicans using the superoxide (O2-) generator
      paraquat (PQ). The effects of PQ on AmB activities against growth, viability,
      membrane permeability and respiration were examined in a wild-type parent strain
      (K) and a respiration-deficient mutant (KRD-19) since PQ-induced superoxide
      generation depends on respiration. In the parent strain, the minimal inhibitory
      concentration (MIC) of AmB, 0.25 microg/ml, tested with a liquid culture was
      lowered to 0.025 microg/ml by 1 mM PQ. Such a PQ-induced decrease in the MIC
      value of AmB was minimal in the mutant. Similar PQ-induced enhancement of AmB
      activity toward the parent strain was also observed with growth on an agar
      medium. In viability tests, when candidal cells were exposed to AmB (0.1
      microg/ml) for I h, the lethality of AmB was enhanced by 1 mM PQ only in the
      parent strain. Exogenous superoxide dismutase and catalase failed to diminish the
      enhancing effect of PQ on the growth inhibitory activity of AmB in the parent
      strain, suggesting an interaction between superoxide and AmB in candidal cells.
      The enhancement of AmB activity by PQ, observed preferentially in the wild-type
      strain, can be explained by extensive superoxide generation depending on
      respiration. These results suggest that oxidative damage induced by superoxide is
      involved in AmB activity against C. albicans.

PMID- 15487315
TI  - Cytokine quantification in the supernatant of mononuclear cell cultures and in
      blood serum from patients with Jorge Lobo's disease.
AB  - Few studies are available about the participation of the immune response in the
      control or the development of Jorge Lobo's disease. Thus, the objective of the
      present study was to quantify macrophage and lymphocyte cytokines in the
      supernatant of cell cultures and in blood serum from patients with this disease.
      The study was conducted on 15 patients with the mycosis and on 15 healthy adult
      individuals (control group). Blood samples were collected in order to obtain
      serum and mononuclear cells. Monocytes were cultured for 24 h in the presence or
      absence of LPS and L. loboi, and lymphocytes were cultured for 48 h in the
      presence or absence of PHA and L. loboi. Cytokines IL-1beta, TNF-alpha and IL-6
      were quantified by ELISA in the supernatants of monocyte cultures and in serum.
      Cytokines IL-2, IFN-gamma, IL-4 and IL-10 were quantified by FLISA in the
      supernatants of lymphocyte cultures and in serum. The quantification of the
      cytokines in the culture supernatant revealed a greater IL-4 and IL-6 production
      and lower IL-2 levels in patients compared to control. The production of IL
      1beta, TNF-alpha, IL-10 and INF-gamma was similar in patients and controls. The
      mononuclear cells from patients with the non-localized form of the disease
      produced higher INF-gamma levels than those of patients with the localized form.
      The results suggest that patients with Jorge Lobo's disease show altered cytokine
      profiles represented by a predominance of the Th2 profile. However, further
      studies are needed to assess the participation of cytokines in the cell-fungus
      interaction in situ.

PMID- 15487316
TI  - Serotype and PCR-fingerprints of clinical and environmental isolates of
      Cryptococcus neoformans in Chiang Mai, Thailand.
AB  - From May 1999 to April 2000, serotypes of clinical and environmental isolates of
      Cryptococcus neoformans were studied in Chiang Mai province, northern Thailand.
      Three hundred and eighty-five environmental samples, of which 100 were dove
      droppings, 55 pigeon droppings and 230 eucalyptus flower, were collected from 7
      Amphoes in Chiang Mai. C. neoformans was isolated from 45 of 100 (45.0%) dove
      dropping samples, 9 of 55 (16.4%) pigeon dropping samples and 2 of 230 (0.9%)
      eucalyptus flower samples. Serotypes of 56 environmental isolates and 75 clinical
      isolates of C. neoformans,obtained during the same period, were determined by the
      slide agglutination test. Fifty-six environmental and 74 clinical isolates
      belonged to C. neoformans serotype A (C. neoformans var. grubii), and only one
      clinical isolate belonged to C. neoformans serotype AD. The isolation of C.
      neoformans var. grubii from eucalyptus flower samples suggests contamination of
      avian droppings. PCR-fingerprinting, using (GACA)4 as a primer, discriminated 131
      clinical and environmental isolates into 2 groups (group I and II). Seventy-five
      clinical and 54 environmental isolates were of group I, which had two major
      specific bands of approximately 1,250 and 960 base pairs. Two environmental
      isolates, one from pigeon excreta and the other from a eucalyptus flower sample
      were of group II, which had two major specific bands of approximately 1,180 and
      500 base pairs.

PMID- 15487317
TI  - Inhibitory effect of Aspergillus fumigatus extract on matrix metalloproteinases
      expression.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) play a role in several physiologic
      and pathologic events. There are some evidence indicating the involvement of MMPs
      in the pathophysiology of fungal infections. METHODS: Here we study somatic
      extract of Aspergillus fumigatus. The influence of Aspergillus vs. two other
      fungal extracts on MMPs production by Fibrosarcoma cell line was investigated
      using an in vitro cytotoxicity assay, sodium dodecyl sulfate-polyacrylamide and
      gelatin zymography. RESULTS: Comparative dose-dependent inhibitory effects on
      MMPs were seen by A. fumigatus extract and compared with some steroidal and non
      steroidal drugs. Cytotoxicity analysis of our extract revealed much lower cell
      death than other examined agents. CONCLUSIONS: Since inhibition of MMPs activity
      has been employed in modality therapy in such diseases as cancer, this extract
      might be promising in the preparation of anti-MMP therapeutic derivatives.

PMID- 15487318
TI  - Genotypic differences of Candida albicans and C. dubliniensis isolates related to
      ethnic/racial differences within the same geographic area.
AB  - Candida albicans and C. dubliniensis genotype differences among Israeli ethnic
      groups were assessed. Isolates from Jews (51), Arabs (35) and Druze (25) were
      genotyped. The distributions among ethnic groups were not different, however they
      differed (p = 0.002) from global populations. Therefore, C. albicans and C.
      dubliniensis genotype distribution differences in Israel are related to changes
      in all ethnic groups.

PMID- 15487319
TI  - The first isolation of Cryptococcus neoformans from Eucalyptus trees in South
      Aegean and Mediterranean Regions of Anatolia in Turkey despite Taurus Mountains
      alkalinity.
AB  - Eucalyptus trees are widespread in subtropical parts of Turkey that have alkaline
      environments due to the soil structure of Taurus Mountains. In this study, the
      existence of Cryptococcus neoformans in eucalyptus trees in the South Aegean and
      Mediterranean Regions of Anatolia, Turkey, was screened between March 1998 and
      September 2002. Only one strain of Cryptococcus neoformans var. grubii (Serotype
      A) was isolated from 1175 eucalyptus samples including debris and flowers in
      culture by Guizotia abyssinica agar. The environmental niche of the isolate was
      Eucalyptus camaldulensis Dehn in the Gokova Region, in the western part of the
      Taurus Mountains. In this study, the existence of Cryptococcus neoformans was
      shown in the eucalyptus flora of Turkey despite the alkaline soil condition.

PMID- 15487320
TI  - Candiduria in hospital patients: a study prospective.
AB  - The presence of Candida species in the urine is frequent among hospitalized
      patients. We studied sample urine of 205 hospitalized patients during a 1-year
      period to determine the incidence of nosocomial candiduria. The yeasts were
      isolated in 22% (45/205) urine cultures and risk factors in these patients were
      analyzed. Candida albicans was isolated in 35.6% and C. tropicalis (22%) was the
      second most frequent species isolated. Most patients were women (57.8%) with a
      mean age of 48.7 years. The principal risk factors that were observed in patients
      with candiduria included antibiotics therapy (100%), urinary catheterization
      (84.4%), surgical procedure (66.7%), female sex and extended hospitalization. The
      efficacy of fluconazole therapy to eradicate Candida from urine was demonstrated
      (p =0.05). Of the 23 individuals who received antifungal therapy, candiduria
      persisted in 9 (39.2%) and of 22 patients who received no antifungal therapy, the
      candiduria persisted in 15 (68.2%).

PMID- 15487321
TI  - Sporotrichosis successfully treated with terbinafine and potassium iodide: case
      report and review of the literature.
AB  - Sporotrichosis is rare in Turkey. We report a 40-year-old woman who had
      subcutaneous sporotrichosis caused by sporothrix schenckii that was successfully
      treated with terbinafine (250 mg, twice a day) for a period of 6 months. She
      received a saturated solution of potassium iodide orally for two months.
      Terbinafine and potassium iodide are suggested to be the agents of choice for
      treatment of subcutaneous sporotrichosis.

PMID- 15487322
TI  - Paracoccidioidomycosis in a woman with idiopathic hirsutism.
AB  - Paracoccidioidomycosis, especially the chronic pulmonary form of the disease, is
      not commonly described in females. Data from in vitro and vivo studies support
      the hypothesis that estrogens might influence the pathogenesis of
      paracoccidioidomycosis in humans by inhibition of transition of conidia or
      mycelia to yeast form of Paracoccidioides brasiliensis. The authors describe a
      chronic progressive pulmonary form of paracoccidioidomycosis in a woman with
      idiopathic hirsutism. In addition to estrogens, the present report suggests that
      other hormonal factors might play an important role in the pathogenesis of
      paracoccidioidomycosis, including the increased production of 5alpha
      dehydrotestosterone frequently described in individuals with idiopathic
      hirsutism.

PMID- 15487323
TI  - Entomopathogenic fungi from 'El Eden' Ecological Reserve, Quintana Roo, Mexico.
AB  - Entomopathogenic fungi were isolated and identified from insects collected from
      the tropical forest and an agricultural area at El Eden Ecological Reserve,
      Quintana Roo, Mexico. These fungi were studied to determine their potential as
      biological control agents of greenhouse Trialeurodes vaporariorum (Homoptera:
      Aleyrodidae), and to contribute to the knowledge of biodiversity of this area. No
      pest insects were observed in the tropical forest. In contrast, all insects
      collected in the agricultural area were considered important pests by the local
      farmers, with the whitefly, as the most relevant, plentiful in Cucurbitaceae
      plants. From approximately 3400 collected insects in three different surveys,
      different anamorphic Ascomycetes were recovered. One isolate of Aspergillus sp.,
      two of Penicillium sp., three of Paecilomyces marquandii, and three of
      Verticillium sp. out of 308 insects (2.9%) from three insect orders, Hymenoptera,
      Diptera and Isoptera in the tropical forest. In contrast, a higher number of
      fungal isolates were recovered from the agricultural area: three isolates from
      Aspergillus parasiticus, 100 of Fusarium moniliforme, one of Aschersonia sp., and
      246 of Fusarium oxysporum out of 3100 insects (11.3%) from three insect orders,
      Homoptera, Coleoptera and Lepidoptera. The results of this study show Fusarium
      moniliforme and F oxysporum as highly virulent to infected insects in the
      agricultural area, with 100 and 246 isolates respectively, out of 350 infected
      insects of 3100 studied specimens. Laboratory whitefly nymph bioassays with
      isolates Ed29a of F. moniliforme, Ed322 of F. oxysporum, and Ed22 of P marquandii
      showed 96 to 97.5% insect mortality with no significant differences (P < 0.05)
      among them. F. oxysporum Ed322 produced no mortality when inoculated on tomato,
      bean, squash and maize seedlings (with and without injuries) compared to the 100%
      mortality caused by phytopathogenic strains, F. oxysporum f. sp. lycopersici and
      F. oxysporum f. sp. radicis lycopersici.

PMID- 15487324
TI  - Correlation between gliotoxin production and virulence of Aspergillus fumigatus
      in Galleria mellonella.
AB  - Aspergillus fumigatus is a pathogenic fungus capable of causing both allergic
      lung disease and invasive aspergillosis, a serious, life-threatening condition in
      neutropenic patients. Aspergilli express an array of mycotoxins and enzymes which
      may facilitate fungal colonisation of host tissue. In this study we investigated
      the possibility of using the insect, Galleria mellonella, for in vivo
      pathogenicity testing of Aspergillus species. Four clinical isolates of
      Aspergillus fumigatus and a single strain of Aspergillus niger were characterised
      for catalase and elastase activity and for the production of gliotoxin. Gliotoxin
      is an immunosuppressive agent previously implicated in assisting tissue
      penetration. Results illustrated a strain dependent difference in elastase
      activity but no significant difference in catalase activity. Gliotoxin production
      was detected in vitro and in vivo by Reversed Phase-High Performance Liquid
      Chromatography, with highest amounts being produced by A. fumigatus ATCC 26933
      (350 ng/mg hyphae). Survival probability plots (Kaplan-Meier) of experimental
      groups infected with Aspergillus conidia indicate that G. mellonella is more
      susceptible to fungal infection by A. fumigatus ATCC 26933, implicating a
      critical role for gliotoxin production rather than growth rate or enzymatic
      activity in the virulence of A. fumigatus in this model.

PMID- 15487325
TI  - Diagnosis of clinical bovine mastitis by fine needle aspiration followed by
      staining and scanning electron microscopy in a Prototheca zopfii outbreak.
AB  - Biopsy by fine needle aspiration together with microbiological examination and
      scanning electron microscopy were evaluated in diagnosis of clinical bovine
      mastitis in a Prototheca zopfii outbreak. Fine needle aspiration was performed in
      21 mammary quarters from ten Holstein cows presenting clinical mastitis caused by
      P. zopfii. The algae were previously identified in the microbiological
      examination of milk collected from these cows. Material aspirated from these 21
      mammary glands was submitted to cytological staining (Gram, Giemsa and/or Shor
      staining). Fine needle aspiration enabled cytological identification of the algae
      in these 21 mammary glands, from which P. zopfii was isolated in the milk.
      Simultaneously, five mammary fragments collected by fine needle aspiration from
      these 21 mammary glands presenting clinical mastitis were also submitted to
      microbiological examination. P. zopfii was also isolated from these five
      fragments. Scanning electron microscopy technique also identified three of these
      five P zopfii strains isolated from mammary fragments collected by cytological
      aspiration. These results suggest that fine needle aspiration may be an
      alternative method for the diagnosis of clinical mastitis.

PMID- 15487326
TI  - Protein translation inhibition by Stachybotrys chartarum conidia with and without
      the mycotoxin containing polysaccharide matrix.
AB  - Recent studies have correlated the presence of Stachybotrys chartarum in
      structures with SBS. S. chartarum produces mycotoxins that are thought to produce
      some of the symptoms reported in sick-building syndrome (SBS). The conidia
      (spores) produced by Stachybotrys species are not commonly found in the air of
      buildings that have been found to contain significant interior growth of this
      organism. This could be due in part to the large size of the Stachybotrys spores,
      or the organism growing in hidden areas such as wall cavities. However,
      individuals in buildings with significant Stachybotrys growth frequently display
      symptoms that may be attributed to exposure to the organism's mycotoxins. In
      addition, Stachybotrys colonies produce a "slime" or polysaccharide
      (carbohydrate) matrix that coats the hyphae and the spores. The intent of this
      project was to determine whether the carbohydrate matrix and the mycotoxins
      embedded in it could be removed from the spores by repeated washings with either
      aqueous or organic solvents. The results demonstrated that the process of spore
      washing removed compounds that were toxic in a protein translation assay as
      compared to spores that were washed with an organic solution, however a
      correlation between carbohydrate removal during the washing process and the
      removal of mycotoxins from the spore surface was not observed. These data
      demonstrated that mycotoxins are not likely to be found exclusively in the
      carbohydrate matrix of the spores. Therefore, mycotoxin removal from the spore
      surface can occur without significant loss of polysaccharide. We also showed that
      toxic substances may be removed from the spore surface with an aqueous solution.
      These results suggest that satratoxins are soluble in aqueous solutions without
      being bound to water-soluble moieties, such as the carbohydrate slime matrix.

PMID- 15487327
TI  - Production of fumonisins by Fusarium verticillioides strains on solid and in a
      defined liquid medium--effects of L-methionine and inoculum.
AB  - In order to evaluate the toxicological and carcinogenic effects of fumonisins,
      large amounts of fumonisins need to be purified, which requires optimal
      conditions for production in culture. Five strains of F. verticillioides were
      compared for their ability to produce fumonisins in solid and liquid media with
      and without the addition of methionine, a fumonisin precursor. Inoculations were
      made either with lyophilized cultures or a concentrated inoculum. Growth in
      liquid medium, measured by biomass, was directly correlated to total fumonisin
      production when a lyophilized inoculum was used. Fumonisin production was
      stimulated by the addition of 0.2% L-methionine to solid media for most strains.
      Levels ranged from 1500-3900 mg/kg in rice, and 2900-12500 mg/kg in maize
      cultures inoculated with lyophilized cultures; 200-4800 mg/kg in rice, and 1500
      4200 mg/kg in maize cultures inoculated with concentrated inoculum. Strains that
      produced relatively high levels of fumonisins in solid media did not necessarily
      do so in liquid medium and vice versa. Total fumonisin levels in liquid medium
      ranged from 40-590 mg/l inoculated with lyophilized cultures and < 1-110 mg/l
      inoculated with concentrated inoculum, without adding the precursor. F.
      verticillioides strains therefore varied in their ability to produce fumonisins,
      and conditions for production need to be optimized individually for each strain.

PMID- 15487328
TI  - Mycoflora and potential for mycotoxin production of freshly harvested black bean
      from the Argentinean main production area.
AB  - A mycological survey was carried out, for the first time, on black bean samples
      from the northwestern Argentinean province of Salta in the 1999 harvest season.
      Ten varieties of black beans were evaluated at three locations. Species of the
      genus Alternaria were the most prevalent component of the black bean mycoflora.
      Species of Fusarium, Sclerotinia, Rhizoctonia and Acremonium were also recorded.
      The predominant species of the genera isolated were Alternaria alternata,
      Sclerotinia sclerotiorum, Rhizoctonia solani, Fusarium semitectum and Acremonium
      strictum. An analysis of variance was applied to determine possible differences
      between black bean varieties. Variety FT88/519 was the most susceptible to
      Sclerotinia sclerotinia infection, while the variety DOR 604 was the least
      susceptible. As toxigenic species were recovered, Alternaria toxins, zearalenone
      and trichothecenes may pose a contamination risk for black bean.

PMID- 15487329
TI  - Mycoflora of Iranian maize harvested in the main production areas in 2000.
AB  - Maize is one of the most important cereals produced in, and imported into, Iran.
      The incidences of seed-borne fungi were determined in Iranian maize harvested in
      2000 from four major production areas with different climatic conditions, namely
      Fars, Khuzestan, Kermanshah and Mazandaran provinces. This is the first study to
      compare the mycoflora of maize in the aforementioned areas. Mycological analyses
      showed a predominance of Fusarium species (38.5%), followed by Aspergillus
      species (8.7%), Rhizopus species (4.8%), Penicillium species (4.5%), Mucor
      species (1.1%), and four other fungal genera. Fusarium verticillioides was the
      most prevalent species (83% of Fusarium isolates and 52% of the total
      isolations), with the highest incidence in Mazandaran (59%), a region of Iran
      with the highest rainfall and relative humidity, high rate of esophageal cancer
      (EC) and high levels of fumonisins in maize. Aspergillus flavus was the most
      widely recovered Aspergillus species and 38% of samples were contaminated with
      this potentially aflatoxigenic fungus. The incidence of A. flavus was highest in
      Kermanshah, the province with lowest mean minimum temperature. Penicillium
      species were seen in all the samples and Fars had the highest incidence, with
      highly significant differences when compared to the other three provinces.
      Diplodia species were not isolated from any of the samples examined.

PMID- 15487330
TI  - A coding region in Diaporthe helianthi reveals genetic variability among isolates
      of different geographic origin.
AB  - A set of Diaporthe helianthi isolates collected in different geographic areas was
      studied in order to examine whether different genetic biotypes could be
      responsible for epidemiological differences shown by sunflower stem canker. D.
      helianthi causes serious losses in France and in former Yugoslavia, while the
      pathogen is only sporadically recorded in Italy in spite of conducive
      pedoclimatic conditions. Variability of a D. helianthi coding genomic region,
      evaluated by means of polymerase chain reaction (PCR), Southern blot
      hybridisation and restriction fragments length polymorphism (RFLP), showed a
      conserved homogeneous pattern shared by French and Yugoslavian isolates compared
      with the heterogeneous pattern of Italian isolates. These results are consistent
      with other investigations (IGS and ITS region variability) performed on the same
      set of isolates, allowing a correlation between D. helianthi biotypes, their
      geographic origin and sunflower stem canker epidemiology.

PMID- 15487331
TI  - Synergistic mixtures of fungitoxic monochloro and dichloro-8-quinolinols against
      five fungi.
AB  - Fourteen mono- and dichloro-8-quinolinols were tested against five fungi
      (Aspergillus niger, A. oryzae, Myrothecium verrucaria, Trichoderma viride, and
      Mucor circinelloides) and compared with the fungitoxicity of 8-quinolinol in
      Yeast Nitrogen Base containing 1% D-glucose and 0.088% L-asparagine. All of the
      compounds were more fungitoxic than 8-quinolinol except for the surprising
      activity of 8-quinolinol against A. oryzae. Mixtures of the MICs of monochloro-
      and dichloro-8-quinolinols in which the halogens were in different positions of
      the quinoline ring showed synergism. Comparable mixtures in which one position of
      each compound was occupied by the same halogen showed additive activity. In a
      different study we showed that 3,5,6-, 3,5,7-, 4,5,7-, and 5,6,7-trichloro-8
      quinolinols were not toxic to M. circinelloides, whereas the combinations of the
      correspondingly substituted mono- and dichloro-8-quinolinols as well as 3,6
      dichloro- and 5,7-dichloro-8-quinolinols were inhibitory. This indicated that a
      steric factor can be involved in affecting fungitoxicity.

PMID- 15487332
TI  - Meeting report: Candida and Candidiasis.

PMID- 15487333
TI  - [International insurance medicine].

PMID- 15487334
TI  - [The psychic cross-sectional finding, cardinal point of psychiatric
      psychotherapeutic expertise].
AB  - Expertise is based on history and clinical findings. Anamnestic data and clinical
      results have to be differentiated carefully. Clinical findings are of special
      importance because they are helpful in verifying anamnestic information with
      regard to extent and impairment quality of complaints, plausibility and thereby
      their significance for the expertise. The author is of the opinion that the
      clinical-psychic finding is in danger of being put in the background. With the
      victory of the descriptive diagnosis and the international diagnostic systems ICD
      10 and DSM-IV, some examiners are tempted to rely on the apparent objectivity of
      symptom constellations which they ask for but do not verify with their findings,
      be it in standardised interviews, self-assesment scales or simply in no
      standardised clinical history. In the following publication the author endeavours
      to substantiate the importance and fundamental irreplaceability of the clinical
      psychiatric finding in psychiatric-psychotherapeutic expertise. In addition, the
      author presents his own proposal for a specific expertise finding.

PMID- 15487335
TI  - [Anxiety prevention among schoolchildren].
AB  - The FRIENDS programme is a prevention and early intervention programme, which
      teaches children strategies to cope with anxiety and challenging situations. This
      paper examines the social validity of the German version of the FRIENDS programme
      using data from a large-scale study on the prevention of anxiety disorders in
      schoolchildren, which is funded by the Dr. Karl-Wilder Stiftung. In this paper,
      data of 208 schoolchildren (aged 9 to 12 years) are used. Results show that the
      children and their parents were highly satisfied with the FRIENDS programme.
      Childrens attendance and completion of their homework assignments were very high.
      Both the children and their parents rated relaxation exercises and thinking
      helpful thoughts as being more useful for the children than other skills.
      Treatment acceptability correlated significantly with the childrens clinical
      outcome. The implications of our findings for future research are discussed.

PMID- 15487336
TI  - [Wiplash injury and "railway spine"].
AB  - Although post-traumatic stress disorder was only recently admitted into the
      international classification systems, psychological reactions to traumatic
      incidents have been frequently described for more than 100 years. The article
      deals with the mental reactions to a trauma in different historical situations.
      Included are the "railway spine" injuries of the 19th century, victims of
      accidents where third party liability could be claimed, accident insurance, the
      psychological consequences of National Socialism and whiplash injury. The
      analysis suggests that different reactions don't describe an identical disorder.
      It seems that reactions to injuries are mainly influenced by the historical and
      social background and the fact of beeing insured.

PMID- 15487338
TI  - [RSI-repetitive strain injury--a work-related disease?].
AB  - It is not scientifically proven that problems in the neck, shoulder, arm and hand
      which patients complain of after repetitive activities at work, are due to
      structural damage caused by physical stress at the workplace. As a consequence,
      from the orthopedic point of view, RSI cannot be accepted as a work-related
      disease.

PMID- 15487337
TI  - [The reliability of conclusions based on hair mineral analysis in individual
      diagnostic].
AB  - The advantages of ubtaining samples for hair mineral analysis (HMA) as well as
      the possibility to measure former exposures and in addition to carry out segment
      analysis make it desirable to work with HMA in order to find a diagnosis. The
      laboratories which offer HMA differ distinctly in their procedure of analysis and
      quality control. HMA is generally not usable for individual diagnostic with two
      exceptions (arsenic and methylmercury) because of the large number of factors of
      individual and environmental influences and sources of error of the method of
      analysis. HMA can be used for cadmium, lead, and zinc in order to compare a
      single person with a larger population. Further research into the relationship of
      content of elements in hair and other tissues of the body is desirable.

PMID- 15487339
TI  - [Origin, character and history development of the idea of science--Part II].

PMID- 15487340
TI  - [Who defines "medical standard"? Imponderable aspects in expert assessment of
      malpractice accusations exemplified by damage to the accessory nerve in neck
      sentinel lymph node excision].

PMID- 15487341
TI  - [Unsystematic preventive examination with electron beam tomography].

PMID- 15487342
TI  - [A new laboratory method for early detection of kidney diseases?].

PMID- 15487343
TI  - [Genetic and chromosomal control of development].
AB  - The last decade has been characterized by extraordinary progress in studies of
      the molecular mechanisms underlying the gene control of development: complexes of
      genes with a hierarchic principle of functioning have been identified,
      evolutionary-conservative systems of genes have been studied that ensure the
      transmembrane regulatory signaling between cells and play a key role in
      morphogenesis, and a concept of gene networks that coordinate gene interaction
      was introduced. Note that temporal and tissue-specific parameters of gene
      expression are correctly realized only in terms of chromosomes and are largely
      determined by the gene position on a chromosome and in the interphase nucleus.
      The epigenetic inheritance of gene status in cell generations is realized at the
      chromosomal level alone due to the cellular or chromosomal memory. This
      ontogenetic memory is an immanent property of a chromosome and cis-regulation
      plays a key role in its maintenance.

PMID- 15487344
TI  - [Polypeptide growth factors in embryogenesis and tumor growth].
AB  - Polypeptide growth factors, which belong to different families (epidermal growth
      factors, insulin-like growth factors, fibroblast growth factors, transforming
      growth factors-beta, and some others), were characterized regarding their
      specific role in embryogenesis and tumor growth. Differences and parallels of the
      functioning of growth factors in these processes have been noted. Potential
      significance of the described characteristics of growth factors for directed
      modulation of embryogenesis and tumor growth is discussed.

PMID- 15487345
TI  - [On donor-acceptor relations and growth correlation in shoot development of the
      pedunculate oak germling].
AB  - We studied the first cycle of shoot growth of the Quercus robur germlings in
      which the donor-acceptor relations were changed by removing a part of cotyledons,
      growing in darkness, or removing growing leaf blades. In all cases, the greatest
      changes in growth and growth correlations were observed in the shoot upper
      metameres carrying leaf blades and the least, in lower metameres preformed in the
      acorn embryo. The removal of growing leaves changed the rhythm of shoot growth.

PMID- 15487346
TI  - [Structure of flower in Arabidopsis thaliana: spatial pattern formation].
AB  - Morphological analysis of flowers was carried out in Arabidopsis thaliana wild
      type plants and agamous and apetala2 mutants. No direct substitution of organs
      takes place in the mutants, since the number and position of organs in them do
      not correspond to the structure of wild type flower. In order to explain these
      data, a notion of spatial pattern formation in the meristem was introduced, which
      preceded the processes of appearance of organ primordia and formation of organs.
      Zones of acropetal and basipetal spatial pattern formation in the flower of wild
      type plants were postulated. It was shown that the acropetal spatial pattern
      formation alone took place in agamous mutants and basipetal spatial pattern
      formation alone, in apetala2 mutants. Different variants of flower structure are
      interpreted as a result of changes in the volume of meristem (space) and order of
      spatial pattern formation (time).

PMID- 15487347
TI  - [Morphogenesis in planarians Dugesia tigrina].
AB  - We carried out computer morphometry in regenerates of planarians Dugesia tigrina.
      The blastema growth was analyzed in fragments of planarians after their fission
      and after transverse transection at different body levels. The blastema was
      growing at a higher rate on tail fragments than on the head fragments and the
      growth rate was the higher, the closer the transection was to the head end. After
      fission, the blastema was growing at a slower rate than after transection in the
      fission zone. The growth of adjacent blastemas formed on both sides after fission
      or transection proceeded at different rates as a function of new body polarity.

PMID- 15487348
TI  - [Specific features of digestive function development in larvae of some salmonid
      fish].
AB  - We studied the activities of digestive enzymes responsible for the digestion of
      food carbohydrate and protein components in plant-eating fish at various stages
      of larval development. The activities of all digestive enzymes tend to rise
      during larval development. Species specific features of the alimentary canal
      functioning have been described.

PMID- 15487349
TI  - [Evaluation of the role of uniparental disomy in early embryolethality of man].
AB  - We carried out systematic studies of the contribution of uniparental disomy for
      eight human chromosomes, 2, 9, 11, 15, 16, 19, 20, and 21, to the etiology of
      spontaneous mortality of human embryos. Most of these chromosomes have regions
      with orthologous imprinted genes syntenic with those on mouse chromosomes, the
      disturbed expression of which is related to embryolethality in mice. Screening of
      uniparental disomy in spontaneous 5- to 16-week abortuses was performed by
      evaluation of the pattern of inheritance of alleles of polymorphic microsatellite
      loci located in the studied chromosomes. A total of 100 human embryos with
      cytogenetically determined normal karyotype were studied, in which arrest at the
      early stages of intrauterine development was determined by ultrasound examination
      of pregnant women. During this study, 13 embryos were discarded due to karyotype
      anomalies or nonpaternity. No cases of uniparental disomy were found among the 87
      studied abortuses for any of chromosomes studied. The analysis of the results of
      this study and four other studies concerning the search for uniparental disomy in
      dead embryos and fetuses did not reveal its elevated frequency in spontaneous
      abortuses as compared to the theoretically expected value based on evaluation of
      the probable combination of meiotic errors in human gametes. The data we obtained
      suggest that, first, uniparental disomies for human chromosomes that have regions
      with orthologous imprinted genes syntenic with mouse chromosomes do not
      contribute noticeably to the death of human embryos at the early developmental
      stages and, second, the mechanisms underlying embryolethality as a result of
      disturbed expression of imprinted loci differ markedly in mammals evolutionarily
      remote from one other.

PMID- 15487350
TI  - [Discovery of genes active in embryogenesis by gene trapping].
AB  - Gene trapping is one of the most promising technologies of vector mutagenesis
      used for discovery of genes active in embryogenesis. A brief description is
      provided for gene trapping based on the use of embryonic stem cells and vectors
      carrying the reporter gene lacZ without promoter, as well as the results obtained
      with the help of this technology. A total of four transgenic mouse lines were
      obtained, in three of which the vector was integrated into genes active during
      embryogenesis. As a result, various patterns of beta-galactosidase expression
      were observed in the limb rudiments, heart, liver, and other organs at different
      embryonic stages. At present, detailed studies of the site and time of action of
      the mutated genes in embryonic and postnatal development are under way, as well
      as molecular-genetic identification of these genes.

PMID- 15487352
TI  - Teaching and learning in general practice.

PMID- 15487351
TI  - [Age-related features of cataractogenesis in salmon fry. 3. Age-related dynamics
      of liver lipid composition during cataractogenesis].
AB  - When studying the cataract pathogenesis in salmon fry, we found changes in the
      content of individual; phospholipid fractions and fatty acid composition in the
      liver of diseased and healthy fish. The age-related changes correlated with the
      increased antioxidant activity and decreased liver content of malondialdehyde.

PMID- 15487353
TI  - Meningococcal vaccine.

PMID- 15487354
TI  - PCR analysis.

PMID- 15487355
TI  - Anal itch.

PMID- 15487356
TI  - Papal blessing.

PMID- 15487358
TI  - General practitioners in teaching practices.

PMID- 15487357
TI  - Good vulval care.

PMID- 15487359
TI  - Surviving the FRACGP and staying sane.
AB  - BACKGROUND: The Royal Australian College of General Practitioners Fellowship
      (FRACGP) examination remains the sole point of entry to Fellowship of the RACGP
      for registrars in the Australian General Practice Training Program. It is also
      used by 'practice eligible route' candidates. It may have been some time since
      candidates studied for any exam, and the prospect is often daunting. Like ally
      examination, the FRACGP has its own attendant myths and legends on what you must
      do to pass. OBJECTIVE: This article recounts the study habits of a group of three
      general practice registrars who sat the FRACGP examination at the end of 2003. It
      attempts to give a light hearted account of their study techniques in the hope of
      dispelling some of the fear and mystery surrounding the exam. DISCUSSION: Despite
      the seemingly casual approach described below, all the authors passed without
      suffering grievous psychological injury, and most of their patients seem to have
      survived as well.

PMID- 15487360
TI  - Flexible teaching and learning in general practice.
AB  - BACKGROUND: Changing general practice workforce characteristics, with fewer
      people prepared to work excessive hours, mean that both teachers and learners
      need greater flexibility in their approach. OBJECTIVE: This article describes the
      strategies one practice has used in aiming for optimum and stimulating medical
      education. Issues such as finding the right match between learner and teacher,
      and enriching the learning environment are discussed. Personal, professional and
      workforce boundaries are examined, as is the maintenance of identity and
      integrity. DISCUSSION: Flexible teaching and learning needs to involve vertical
      and horizontal integration. Mentors who are thriving personally should lead by
      example. A nonclinical agenda is paramount. Appropriate accreditation within the
      training program and acknowledgment of the differences between rural and
      metropolitan general practice training needs further work.

PMID- 15487361
TI  - Giving feedback to learners in the practice.
AB  - BACKGROUND: Many general practitioners accept vocational registrars and medical
      students into their practice. Giving feedback to students on their work
      performance is an essential component of teaching in general OBJECTIVE: This
      article examines the central role of feedback in the teaching of medical students
      and registrars and provides practical guidelines on how to provide feedback in
      the setting of a busy general practice, describes some barriers and pitfalls, and
      provides a registrar's perspective on what learners see as important. DISCUSSION:
      For feedback to be effective, it must be given in a supportive environment.
      Feedback that is specific to the learner performance is highly valued by
      learners, whereas nonspecific evaluative feedback is less valued. The mentoring
      relationship between teacher and learner is crucial to giving effective feedback.
      Learners appreciate a teacher's help identifying any area for improvement, then
      being given the chance to work out the answers for themselves instead of being
      told exactly what to do by the more experienced teacher.

PMID- 15487362
TI  - Practice based assessment.
AB  - BACKGROUND: Practice based assessment (PBA) was designed to suit the needs of
      doctors eligible to sit The Royal Australian College of General Practitioners
      Fellowship (FRACGP) exam via the practice eligible route. A pilot program of the
      PBA was undertaken in 2000. As a result of recommendations by candidates and
      examiners and ongoing literature review, a number of changes have been made, but
      the basic structure of the assessment process remains. OBJECTIVE: This article
      describes the components of the PBA route to the FRACGP and discuss how
      candidates can prepare effectively for their assessment. DISCUSSION: The PBA
      involves five components: an enrolment submission including details of general
      practice experience curriculum vitae and details of continuing professional
      development; a professional portfolio including evidence of CPR proficiency, a
      practice profile and a list of 25 professional peers who have shared the care of
      patients; videotape of 90 consultations; an examiner clinical visit; and a 20
      question viva.

PMID- 15487363
TI  - Management of the impaired doctor.
AB  - BACKGROUND: The lifetime prevalence of substance abuse disorders among doctors in
      Australia has been estimated to be approximately 8%. These disorders can
      interfere with a doctor's ability to function and pose a risk to patient welfare
      and safety.' OBJECTIVE: This article identifies key indicators to the development
      of problem alcohol and drug use in a general practitioner, associated possible
      psychiatric morbidity, work deficits, and the need for colleagues to recognise
      and respond in a timely manner to resolve these events. DISCUSSION: Where
      intervention, treatment and monitoring are initiated early in problem drug use,
      outcomes for the GP are typically positive. Outcomes are better where there is
      adequate support by friends and colleagues, and where there is a clearly defined
      management strategy.

PMID- 15487364
TI  - The growing challenge of party drugs in general practice.
AB  - BACKGROUND: 'Party drugs' are commonly used by young people to enhance feelings
      of sociability, mood and sexual arousal. Recent studies suggest the prevalence of
      party drug use is increasing with more than 1 million Australians using party
      drugs. The potential for morbidity is high with increasing polydrug use.
      OBJECTIVE: This article aims to provide practical information for the general
      practitioner in the assessment and management of patients presenting with party
      drug related problems. DISCUSSION: People that use party drugs can present in
      general practice with a variety of symptoms and signs depending on the drug used.
      Importance is often placed on identifying the drug, but it is more important to
      engage the user and explore the drug using behaviour. While cessation of party
      drug use may be influenced by many things including GP advice, the natural
      history is eventual cessation, and GPs have a key role in promoting harm
      minimisation strategies and ongoing health care in the meantime.

PMID- 15487365
TI  - What's in the doctor's bag?
AB  - BACKGROUND: A doctor's bag is invaluable when you need to take part of the
      practice to the patient, or in the case of an emergency. OBJECTIVE: This article
      aims to help new general practice registrars and experienced general
      practitioners consider what they may need in their doctor's bag. DISCUSSION: The
      doctor's bag needs to be personalised to the requirements of each GP and their
      patient population. Decisions need to be made about the type of bag, stationery,
      equipment and medications carried. Some possible additions for a rural doctor's
      bag are included, as well as some general tips.

PMID- 15487367
TI  - Patient education. I'm pregnant. Should I have these tests?

PMID- 15487366
TI  - STIs in pregnancy. An update for GPs.
AB  - BACKGROUND: Pregnancy and sexually transmitted infections (STIs) are both
      consequences of unprotected vaginal sex. In addition to causing maternal
      morbidity in their own right, many STIs including human immunodeficiency virus
      (HIV) can be transmitted to the neonate. Antenatal screening during pregnancy
      provides an opportunity to minimise or eliminate the antepartum, intrapartum and
      postpartum consequences of most STIs. OBJECTIVE: This article discusses the
      diagnosis, management and treatments available for STIs in pregnancy to minimise
      morbidity and mortality for both mother and child. DISCUSSION: HIV testing in
      antenatal care should be added to routine syphilis and hepatitis B serology, as
      effective HIV interventions can significantly reduce the risk of mother-child
      transmission. Consideration should be given to testing in women less than 25
      years of age for chlamydia and those women at increased sexual risk. Male
      partners should not be forgotten and contact tracing, treatment and follow up
      offered. Due to the very small risk associated with genital warts and genital
      herpes, normalisation, information and reassurance are appropriate for the
      majority of women affected.

PMID- 15487368
TI  - Pupil disorder. Eye series--19.

PMID- 15487369
TI  - Teaching and learning in rural general practice.

PMID- 15487370
TI  - Failure to diagnose: melanoma.
AB  - Case histories are based on actual medical negligence claims, however, certain
      facts have been omitted or changed by the author to ensure the anonymity of the
      parties involved. Medical negligence claims alleging 'failure to diagnose' are a
      common cause of claims and complaints against general practitioners. This article
      outlines some risk management strategies designed to minimise the possibility of
      an adverse event arising from failure to diagnose melanoma.

PMID- 15487371
TI  - Meaninglessness.

PMID- 15487372
TI  - Overseas trained doctors. How to prepare for a fellowship exam.
AB  - Exam preparation is a stressful time and everyone wants to prepare effectively to
      do as well as they can. It is a personal challenge that, successfully overcome,
      carries the reward of peer recognition and acceptance. However, for the overseas
      trained doctor it is not easy to write a fellowship exam when one is not sure
      either where or how to start, where to get help and resources, and how to
      proceed. I encountered many difficulties in preparing for the Fellowship of The
      Royal Australian College of General Practitioner (FRACGP) exam, and in overcoming
      these difficulties, thought the knowledge acquired may be useful to others facing
      the same task.

PMID- 15487373
TI  - GP claims for completing diabetes 'cycle of care'.
AB  - BACKGROUND: There is a wide variability in the level of claims for diabetes.
      Service Incentive Payments (SIP) by general practitioners. METHOD: Cross
      sectional comparison of the ratio of the number of SIP items claimed between
      August 2002 and July 2003 to the estimated prevalence of diabetes by divisions of
      general practice (DGP). PARTICIPANTS AND SETTING: Seventy-nine of the 101 DGP
      with diabetes programs in 2002. RESULTS: The average ratio of diabetes SIP claims
      to estimated diabetes prevalence (including both diagnosed and undiagnosed cases)
      for each quarter of the year between August 2002 and July 2003 was 10.1%
      (standard deviation 3.6). This ratio was higher in DGP with a more disadvantaged
      population, and more of their GP members in large practices. The provision of IT
      support in DGP and the proportion of GPs who had patients registered on the
      division's register were associated with a higher ratio of claims. A multiple
      regression model with two factors: socioeconomic disadvantage and the proportion
      of GP members in practices of five or more GPs predicted 41% of the variance.
      CONCLUSION: Divisions of general practice appear to be supporting practices
      serving disadvantaged populations to deliver quality care for patients with
      chronic disease. The association with practice size and DGP activities suggests
      that practice organisation and systems are important in the provision of good
      care for patients with chronic disease.

PMID- 15487374
TI  - Randomised trials--cluster versus individual randomisation. Primary Care Alliance
      for Clinical Trials (PACT) network.

PMID- 15487375
TI  - Village birth attendants in Papua New Guinea.
AB  - AIM: To describe the care delivered by village birth attendants in a remote area
      of Papua New Guinea. METHOD: A qualitative study using semistructured interviews
      with 56 voluntary village birth attendants. RESULTS: Village birth attendants
      supervise and assist women with labour and delivery. Many have additional roles
      in their community. Most are motivated by a desire to help the women in their
      community. Common difficulties encountered include obstetric and logistical
      problems. The most common reason for ceasing work is family pressure or lack of
      support. DISCUSSION: Village birth attendants may contribute toward an
      improvement in maternal morbidity and mortality in remote areas of Papua New
      Guinea.

PMID- 15487376
TI  - How to undertake research in general practice. Tips for the novice researcher.

PMID- 15487377
TI  - Pont Du Gard forum: preserving the light.

PMID- 15487378
TI  - Developmental supervision for nurses.
AB  - Developmental supervision is gaining increasing recognition in nursing as a form
      of clinical supervision that will promote professional growth and ultimately lead
      to improved patient care. Benner's (1984) model of career development is used as
      a framework in which to examine appropriate forms of supervision for each
      developmental stage. Directive, collaborative and non-directive supervision are
      applied to each of these developmental levels.

PMID- 15487379
TI  - Building quality practice settings: an attributes model.
AB  - To practice effectively nurses need an environment that supports quality
      professional practice. This article describes the development of a model
      identifying seven (7) key system attributes of a quality practice setting. The
      defined attributes are essential in supporting professional practice and quality
      care. The Quality Practice Setting Attributes Model developed by the College of
      Nurses of Ontario in Canada provides the foundational framework for the Practice
      Setting Consultation Program (PSCP), a unique quality improvement approach to
      creating quality practice environments.

PMID- 15487380
TI  - Clients' and nurses' perspectives on caring as related to nursing leadership--the
      Hellenic dimension. Part One.
AB  - Public perceptions of caring are vital to the future of the nursing profession.
      Literature indicates that patients conceive caring in a traditional manner which
      contrasts with that of nurses. This paper addresses the culturally determined
      complex and interactive personal, historical and sociopolitical factors that
      account for the development of clients' and nurses' perceptions of caring and
      explains the differences observed in research between the two groups. It also
      discusses the high cost that society and nursing pay today for the poor public
      image of nurse caring. Finally, it identifies strategies that nurses, especially
      those in leadership positions, can use to improve the consumer's view of caring
      and to reduce the gap existing between clients' and professionals' perceptions of
      the concept. The Hellenic perspective is used as a reference point to present the
      relevance of the issue to the broader context of nursing in the world. The paper
      is based upon primary and secondary data including research findings,
      legislation, the authors' observations and experiences with their domestic health
      care system, and available literature on the subject.

PMID- 15487381
TI  - [The difficult struggle against breast cancer: implementation and evaluation of
      guidelines for the early diagnosis of breast cancer].

PMID- 15487382
TI  - [A concept for the implementation and evaluation of the guideline "Early
      Detection of Breast Cancer in Germany"].
AB  - Systematically developed, evidence- and consensus-based guidelines are important
      tools for improving health care services. The effectiveness of a guideline does
      not only relate to its methodological quality but also to the implementation
      strategy used. The following paper describes the systematic development of a
      strategy for implementing and evaluating the guideline "Early Detection of Breast
      Cancer in Germany" as part of a national project. A multi-faceted systematic
      implementation strategy has been developed addressing existing barriers and
      building on projects that have recently been introduced in Germany to improve the
      early detection and management of breast cancer. The aim is to induce behavioural
      changes in women as healthcare recipients and physicians as healthcare providers,
      both involved in the medical decision-making process within the scope of the
      guideline. Furthermore, it supports organisational changes to assure compliance
      with the guideline by means of quality assurance and quality management. To
      ensure evaluation of the implementation process a set of quality indicators have
      been identified for the baseline assessment of structures, provider performance
      and outcomes. Both the effectiveness of the implementation process and the
      effectiveness of the guideline itself will be measured by using the same set of
      indicators for reevaluation within a pre-defined time interval of 18 months. The
      quasi-experimental design of this uncontrolled before and after implementation
      study outlined in the present paper allows the assessment of clinically relevant
      changes using quality indicators that measure the effectiveness of the guideline
      on a national level.

PMID- 15487383
TI  - [Short version of the guideline "Early Detection of Breast Cancer in Germany"].
AB  - The aim of this evidence-, consensus- and outcome-based good clinical practice
      guideline is to help physicians, and women in making appropriate healthcare
      decisions about the early detection of breast cancer. The principle of early
      detection of breast cancer comprises the detection and diagnosis of pre-malignant
      breast tumours (UICC stage 0, carcinoma in situ) with a possible cancer risk
      reduction and the detection and diagnosis of breast cancer at an early stage
      (UICC stage 1) with a scientifically proven 90% chance of cure. By establishing a
      nation-wide comprehensive quality assurance program for the early detection of
      breast cancer this guideline lays the foundation for a timely reduction of breast
      cancer mortality and achievement of cure with less impairment of patient's
      quality of life. It would appear that this guideline makes major improvements in
      women's healthcare feasible.

PMID- 15487384
TI  - [Mammogram results in ambulatory care--a mammography quality circle in
      Braunschweig, Germany, between 1998 and 2001].
AB  - Radiologists from seven independent practices in Germany (average number of cases
      3,500 in 2001) combined to form a mammography quality control group.
      Documentation and follow up were standardised for all cases that resulted in a
      referral for open biopsy. A quantitative analysis of the data would be expected
      to clarify the quality achieved in ambulatory care and to show further
      possibilities for quality assurance measures. The first overall analysis of 2,500
      referrals for biopsy from 1998 to 2001 shows differences between practices as
      regards the frequency of referral for biopsy and the proportion of referrals for
      suspected malignancy, which are based on practice-specific conditions (referral
      behaviour, age structure of patients) and individual case management. Practices
      are very close in relation to positive predictive value (ppv) and detection rate.
      The biopsy rate in 2001 slightly exceeded 3%, the overall detection rate was
      1.7%, and ppv 81%. For asymptomatic women detection rate and ppv were 0.5% and
      70%, respectively. Quality parameters for all mammography referrals in total
      exceed those of screening programmes. When restricted to asymptomatic women,
      results have been achieved that are comparable to those of established screening
      programmes. Naturally the patients involved here are those in whom mammography
      was indicated. Nonetheless, these results demonstrate a high quality of detection
      on the part of those performing mammography in routine ambulatory care, and can
      be used as a reference for other types of care. With consistent quality assurance
      in relation to technical considerations and personnel, a performance quality can
      be achieved in independent practices which to date has not been surpassed by
      specialist mammography centres.

PMID- 15487385
TI  - [Centralisation of breast cancer management by giving minimum work-load.
      Empirical effects in the region of North-Rhine, Germany].
AB  - INTRODUCTION: The concentration of treatment on a few hospitals is discussed to
      improve the outcome of care. For the treatment of the breast cancer the
      distributional effects are evaluated. METHOD: A systematic literature search in
      Medline identified six studies dealing with the evidence on the relation between
      outcome and workload. Using administrative data of a sickness fund in the region
      of Rhineland, Germany, the number of hospitals and patients affected by minimum
      work-loads was determined. RESULTS: Study results show that in general a minimum
      workload of 100 to 150 new diagnosed cases per year and hospital is recommended.
      These recommendations would lead to 46% of the presently treating hospitals being
      excluded (minimum work-load of 150 cases; year 2001). If the workload is set to
      100 cases, 31% of the hospitals will be excluded from breast cancer management.
      No significant differences could be detected in the data of the years 2000 and
      2001. DISCUSSION: The association between minimum workload and outcome of care
      seems to be evident. Further studies involving larger regions are needed to
      evaluate the distributional effects and gains of outcome.

PMID- 15487386
TI  - [Are articles in German gynecological journals oriented toward continuing
      education?].

PMID- 15487387
TI  - [An assessment of patient education programmes for patients with type 1 and 2
      diabetes, asthma and COPD, coronary heart disease, hypertension, congestive heart
      failure, and breast cancer in Germany].
AB  - BACKGROUND: Patient education programmes will be a mandatory part of the new
      legislation on disease management programmes for chronic diseases in Germany.
      Today, only little is known about the number, variety and effectiveness of
      implemented patient education programmes in Germany. METHODS: 176 potential
      providers of patient education programmes were identified by literature search,
      Internet search, and interviews with health education experts. We developed a
      semi-structured questionnaire. Assessment of content and quality was conducted in
      two steps by using defined criteria of the Co-ordinating Committee, the Head
      Association of the statutory health insurances and the respective Medical
      Associations: the first step was to check whether the programme had a structured
      teaching concept and whether all requirements for education with respect to a
      given disease had been taken into account. In the second step, we used balance
      sheets for reviewing the strengths and weaknesses of the programmes. RESULTS: 49
      providers handed in 95 pa tient education programmes for assess ment. Due to
      formal mistakes only 91 programmes could be analysed. 49 programmes failed the
      criteria of the first assessment step. For the remaining 42 patient education
      programmes balance sheets were prepared. Areas of the most frequent deficiencies
      included: lack of scientific evaluation of the effectiveness of the programme,
      lack of transparency of cost data, and quality improvement activities.
      CONCLUSIONS: For the purpose of a nation-wide implementation of disease
      management programmes the existing patient education programmes in Germany need
      to be further improved. Single examples demonstrated that the accessible criteria
      of self-management are not sufficient for the evaluation of already established
      patient education programmes.

PMID- 15487389
TI  - [Established certainty: experiences with clinical chaplaincy between doubt,
      evidence and revelation].
AB  - Medicine must not be understood just as applied science. Modern physics, namely
      Quantum Theory, the theory of complementarity, and the "End of Certainty" (Ilya
      Prigogine) have proved the cogency of the perception of medicine as a mixture of
      the art of uncertainty and the science of probability. Research into chaos and
      order has revealed the dynamic structure of complex systems that no longer allow
      for undoubted prognosis. The only thing a physician can definitely promise is his
      readiness never to abandon a patient and to keep up personal integrity. Thus it
      is not only knowledge and skill that matter. It is background and authenticity
      that counts, which will make the doctor a guarantee of a covenant relationship
      that the patient may rely on. The importance of standing surety for someone in a
      therapeutic setting is demonstrated by giving examples from literature and
      personal experience in clinical chaplaincy.

PMID- 15487388
TI  - [The German Guideline Clearinghouse on Breast Cancer: the need for frequent
      updating of breast cancer guidelines requires effective guideline updating
      procedures].
AB  - In order to promote the quality of health care and guidelines in Germany the
      German Guideline Clearinghouse (Sponsors: German Medical Association, National
      Association of the Statutory Health Insurance Physicians, German Hospital
      Federation, Associations of the Sickness Funds and the Statutory Pension
      Insurance) was established at the Agency for Quality in Medicine (AQuMed) in
      1999. The results of the 10th Guideline Clearing Project, the Guideline Clearing
      Report "Breast Cancer", were published in December 2003. In a systematic search
      using English/German language guideline databases and literature databases
      (Medline, Healthstar, Embase), 16 national guidelines were identified which were
      in accordance to the inclusion criteria (breast cancer treatment; German or
      English language; published after 1992; new guideline or genuine update (no
      adaptation); recommended for country-wide implementation). The methodological
      quality of these 16 guidelines was evaluated using the appraisal instrument of
      the German Guideline Clearinghouse, the checklist "Methodological Quality of
      Clinical Practice Guidelines". A peer review of the guidelines was performed by a
      multidisciplinary focus group of experts (intended guideline users from clinical
      and ambulatory settings as well as patients). This group consented comments and
      recommendations for actions of health care policy makers in Germany for a German
      breast cancer guideline based on examples from the appraised guidelines. None of
      the identified guidelines contained information about all of the 24 key topics
      that the focus group considered to be relevant for a German national guideline.
      The selected exemplary text extracts from the evaluated guidelines can be used as
      benchmarks and example sources for the development of a national German breast
      cancer guideline. From the beginning, patients should be involved in the
      development process within a multidisciplinary team. Due to the rapid emergence
      of new evidence, oncology guidelines need an effective procedure for updating in
      order to ensure that they are able to promote health care quality by giving
      current recommendations based on best available evidence. International networks
      such as the Guidelines International Network (G-I-N) will be helpful to collect
      and appraise the evidence for the national guideline development groups in an
      effective way.

PMID- 15487390
TI  - Registering clinical trials is necessary for ethical, scientific and economic
      reasons.

PMID- 15487391
TI  - [Do physicians see their professional autonomy strengthen or weaken? The medical
      profession and the example of evidence-based medicine from a sociological point
      of view].
AB  - The introduction of evidence-based medicine has been discussed vehemently and
      controversially not only in medical but also in sociological journals. Sociology
      is primarily interested in this innovation from the perspective of its impact on
      autonomy and professionalism. The author discusses the possible implications of
      EbM with regard to the question if it increases or decreases the professional
      status of medicine. Both the historical development of this debate and the
      present discourse are being considered.

PMID- 15487392
TI  - [Last but not least--the German Network EbM has got its glossary on EbM terms].
AB  - Evidence-based medicine is not self-explaining. But due to the use of
      methodological, technical and statistical terms beginners might find it difficult
      to get access to EbM. To overcome this hurdle, a working group of practising
      physicians and methodologists have developed a glossary for the German Network
      Evidence-based Medicine covering the most important terms and providing
      explanations by giving practical examples. Access is also possible through
      www.ebm-netzwerk.de/glossar.htm. The present glossary is just a start, though.
      Over the coming years more terms will have to be added according to the needs and
      suggestions of our readership. We thus call on active participation of its users.

PMID- 15487393
TI  - [Physicians and medical care. From the cycle of contracts on "medical rights",
      organized by the Central Committee for quality control in Prussia ] [1904].

PMID- 15487394
TI  - [From the breast cancer registry: breast surgery].

PMID- 15487395
TI  - Radiologic case study. Pipkin type II fracture of the right femoral head.

PMID- 15487396
TI  - Current concepts in joint replacement.

PMID- 15487397
TI  - Minimally invasive plate osteosynthesis in distal tibial fractures: pitfalls and
      surgical guidelines.

PMID- 15487398
TI  - David Halsey on the AAOS Expert Witness Program.

PMID- 15487399
TI  - Are all opioids created equal?

PMID- 15487400
TI  - New insights into the biology of fracture healing.

PMID- 15487401
TI  - John Charnley remembered: regaining our bearings.

PMID- 15487402
TI  - Hip fractures--when to nail and when to bail.

PMID- 15487403
TI  - Peritrochanteric fractures: choosing your weapon!

PMID- 15487404
TI  - Hip fractures in the elderly: on the acetabular side.

PMID- 15487405
TI  - Advancing new technologies: a cautionary tale.

PMID- 15487406
TI  - The mini-incision: occasionally desirable, but rarely necessary.

PMID- 15487407
TI  - The appeal of the mini-incision.

PMID- 15487408
TI  - The rationale for using computer navigation with minimally invasive THA.

PMID- 15487409
TI  - The rise of the machines.

PMID- 15487410
TI  - Osteogenic proteins: a little dab will do ya.

PMID- 15487411
TI  - Bone graft expanders: filling the void.

PMID- 15487412
TI  - The dysplastic hip.

PMID- 15487413
TI  - Proximal femoral deformity: bent but not broken.

PMID- 15487414
TI  - Osteoporosis: an unsolved problem in total hip arthroplasty.

PMID- 15487415
TI  - Avoiding dislocation: but when it happens!

PMID- 15487416
TI  - Trochanteric osteotomy and advancement: a technique for abductor related hip
      instability.

PMID- 15487417
TI  - Is there still a role for the cemented stem?

PMID- 15487418
TI  - Fenestration of the femoral shaft: a standard procedure in revision hip surgery
      without bypassing the cortical defect.

PMID- 15487419
TI  - Impaction grafting for acetabular revision: bringing back the bone.

PMID- 15487420
TI  - The role of cages and rings: when all else fails.

PMID- 15487421
TI  - Nonoperative management of knee arthritis: a little bit of this, a little bit of
      that.

PMID- 15487422
TI  - Articular cartilage injury: filling potholes.

PMID- 15487423
TI  - The role of osteotomy 2003: defining the niche.
AB  - Although the use of traditional high tibial osteotomy in the unicompartmental
      osteoarthritic knee has declined due to high failure rates at 10 years, results
      that are generally poorer than total and unicompartmental arthroplasty, and
      difficulties with conversion to TKR, a potential role for osteotomy still exists.
      As long-term data becomes available to support or refute the renewed enthusiasm
      in the more modern techniques and applications, the indications for osteotomies
      about the knee will become better defined.

PMID- 15487424
TI  - Frequently asked questions regarding total knee arthroplasty.

PMID- 15487425
TI  - Minimizing blood loss after total knee replacement.

PMID- 15487426
TI  - Wound healing problems in TKA: just when you thought it was over!
AB  - Wound healing problems after TKA can be minimized by identifying at-risk
      patients, using postoperative oxygen liberally, careful surgical technique, and
      allowing wound healing to take priority over early motion. If a wound problem
      develops, prompt treatment will decrease the risk of catastrophic deep infection.

PMID- 15487427
TI  - Extensor mechanism problems: what to do, what to do!

PMID- 15487428
TI  - Direct exchange treatment of septic total joint arthroplasty with intra-articular
      infusion of antibiotics: technique and early results.

PMID- 15487429
TI  - Cemented stems are requisite in revision knee replacement.

PMID- 15487430
TI  - Cemented tibial stems are not requisite in revision.
AB  - Tibial stems are necessary in most total knee revisions to share the load and
      protect the fixation interface of the tibial tray. Successful use of a tibial
      stem requires independent stability of the stem with or without cement. Some
      additional geometry on the undersurface of the tibial tray such as peripheral
      pegs or fins is necessary to provide additional resistance to rotatory stresses
      if the stem is not cemented. Cementing the tibial stem works. However, with the
      excellent results of cementless stems, who would want to deal with cement removal
      in those few cases of loosening or the occasional case with infection or
      instability? The disadvantages of a press-fit stem are not seen with modem tibial
      stems, such as with a long conical stem with an offset attachment to the tibial
      baseplate as used in this series. Cement is not necessary!

PMID- 15487431
TI  - Why knees fail.

PMID- 15487432
TI  - The role of implant constraint in revision total knee replacement: striking the
      balance.

PMID- 15487433
TI  - Modular augments in total knee replacement.

PMID- 15487434
TI  - Structural femoral head allografting with revision TKA.

PMID- 15487435
TI  - The multiply operated patient: last resort solutions.

PMID- 15487436
TI  - Competing for a desired reward in the Stroop task: when attentional control is
      unconscious but effective versus conscious but ineffective.
AB  - Recent studies using Stroop's paradigm have shown that word recognition processes
      can be controlled when the local context of the task is manipulated. In the
      present study, factors related to the participants' broader context (i.e.,
      presence vs. absence of a competitor and of a desired reward) were manipulated.
      The results (1) support the conclusion that control of semantic-level activation
      can be unconscious but effective versus conscious but ineffective, (2) suggest
      that unconscious control alone operates on line (i.e., when the participant is
      responding), and (3) clarify the impact of socio-contextual factors that have
      been confounded in past research. Taken together, these findings strengthen the
      view that word recognition processes are controllable and offer new reasons to
      pay constant attention to the social environment of cognition.

PMID- 15487437
TI  - Content and strategy in syllogistic reasoning.
AB  - Syllogistic reasoning has been investigated as a general deductive process
      (Johnson-Laird & Byrne, 1991; Revlis, 1975; Rips, 1994). However, several studies
      have demonstrated the role of cognitive strategies in this type of reasoning.
      These strategies focus on the method used by the participants (Ford, 1995;
      Gilhooly, Logie, Wetherick, & Wynn, 1993) and strategies related to different
      interpretations of the quantified premises (Roberts, Newstead, & Griggs, 2001).
      In this paper, we propose that content (as well as individual cognitive
      differences) is an important factor in inducing a certain strategy or method for
      syllogistic resolution. Specifically, we suggest that syllogisms with a causal
      conditional premise that can be extended by an agency premise induce the use of a
      conditional method. To demonstrate this, we carried out two experiments.
      Experiment 1 provided evidence that this type of syllogism leads participants to
      draw the predicted conditional conclusions, in contrast with control content
      syllogisms. In Experiment 2, we demonstrated that the drawing of conditional
      conclusions is based on a causal conditional to an agent representation of the
      syllogism premises. These results support the role of content as inducing a
      particular strategy for syllogistic resolution. The implications of these results
      are discussed.

PMID- 15487438
TI  - College students' memory for vocabulary in their majors: evidence for a nonlinear
      relation between knowledge and memory.
AB  - The effect of domain knowledge on students' memory for vocabulary terms was
      investigated. Participants were 142 college students (94 education majors and 48
      business majors). The measure of domain knowledge was the number of courses
      completed in the major. Students recalled three different lists (control,
      education, and business) of 20 words. Knowledge effects were estimated
      controlling for academic aptitude, academic achievement, and general memory
      ability. Domain-specific knowledge consistently predicted recall, above and
      beyond the effect of these control variables. Moreover, nonlinear models better
      represented the relation between knowledge and memory, with very similar
      functions predicting recall in both knowledge domains. Specifically, early in the
      majors more classes corresponded with increased memory performance, but a plateau
      period, when more classes did not result in higher recall, was evident for both
      majors. Longitudinal research is needed to explore at what point in learning
      novices' performance begins to resemble experts' performance.

PMID- 15487439
TI  - Effect of arousal on internal clock speed in real action and mental imagery.
AB  - The possible implication of an internal clock as a mechanism accounting for the
      temporal homology between actual and mental walking is studied. To observe this
      phenomenon, stressful sound stimuli were used to increase arousal, which is known
      to activate the internal clock. Seventeen participants performed three tasks: (1)
      a time production task, used as a reference task reflecting the internal clock
      speed; (2) an actual walking task; and (3) a mental walking task, all three in
      two sound conditions (no noise and noise). The results showed a significant
      effect of arousal on time in each task. The effect of noise, increasing the
      arousal level, was greater in time production and mental imagery tasks than in
      real action. In addition, the percentages of change between the two sound
      conditions for actual and mental walking time were not statistically different.
      These findings are further evidence of the existence of a timing process common
      to actual and mental walking. The data are consistent with the implication of an
      internal clock in both actual and mental walking.

PMID- 15487440
TI  - Primacy, recency, and suffix effects in auditory short-term memory for pure
      tones: evidence from a probe recognition paradigm.
AB  - The present study was designed to explore serial position and suffix effects in
      the short-term retention of nonverbal sounds. In contrast with previous studies
      of these effects, a probe recognition paradigm was used to minimize the
      possibility that participants would use a verbal labelling strategy. On each
      trial, participants heard a memory set consisting of three pure tones, followed
      five seconds later by a probe tone. Participants were required to indicate
      whether or not the probe tone had been a member of the memory set. On most
      trials, a suffix sound was presented 1 second following the third sound in the
      memory set. Results revealed that tones presented in the first and last positions
      of the memory set were recognized more accurately than were tones presented in
      the middle position. Furthermore, recognition of sounds presented in the last
      position was compromised when the memory set was followed by a postlist suffix of
      similar pitch, spectral composition, and spatial location.

PMID- 15487441
TI  - The Scarlet Letter.

PMID- 15487442
TI  - 14 tips to prevent musculoskeletal disorders (MSDs).

PMID- 15487443
TI  - The approaching quantitative revolution in diagnostic anatomic pathology.

PMID- 15487444
TI  - Hyalinizing trabecular tumor of the thyroid gland: much ado about nothing?

PMID- 15487445
TI  - Use of Bayes rule and MIB-1 proliferation index to discriminate Spitz nevus from
      malignant melanoma.
AB  - Differentiating Spitz nevus from malignant melanoma is difficult and
      controversial. Despite helpful lists of differential diagnostic features,
      uncertainty about the diagnosis often provokes some to stain the tumor for MIB-1
      antibody to Ki-67 and measure the proliferation index (PI) of the tumor. Of the
      many reports about MIB-1 PI in Spitz nevi and melanoma, none have consolidated
      the information to provide guidelines for the predictive probability that a
      lesion is a Spitz nevus, given that the MIB-1 PI falls into a certain interval.
      The present study used previously published data and exponential and gamma
      probability density functions to model statistical distributions of PI,
      respectively, in Spitz nevi and melanomas and Bayes rule to estimate the
      predictive probability that a lesion is a Spitz nevus, given an observed PI.
      Results indicate that PIs more than 10% favor a melanoma diagnosis and PIs less
      than 2%, Spitz nevus. PI values between 2% and 10% yield various predictive
      values for Spitz nevus, depending on the a priori probability that the lesion is
      a Spitz nevus. The algorithm tabulates guidelines for the predictive
      probabilities of Spitz nevus given an observed PI.

PMID- 15487446
TI  - Hyalinizing trabecular adenoma of the thyroid gland identification through MIB-1
      staining of fine-needle aspiration biopsy smears.
AB  - Smears of fine-needle aspiration (FNA) biopsy specimens of 24 histologically
      proven and MIB-1-positive hyalinizing trabecular adenomas stained with
      Papanicolaou or Diff-Quik were stripped from the original slides, transferred to
      charged slides, destained, and restained with MIB-1. Positive immunoreactivity
      with MIB-1 in a peripheral cytoplasmic pattern was present in 17 specimens, no
      immunoreactivity was seen in 4 specimens, and equivocal staining was seen in 3
      specimens. Papanicolaou-stained smears of papillary thyroid carcinoma, medullary
      thyroid carcinoma, thyroid follicular neoplasm, and Hurthle cell adenoma (5
      specimens each) were treated similarly. None of the control cases stained with
      MIB-1 had the peripheral cytoplasmic pattern. Hyalinizing trabecular adenoma can
      be distinguished reliably from other thyroid neoplasms by MIB-1 staining of
      destained cells from FNA biopsy specimens.

PMID- 15487447
TI  - Prognostic value of cyclin B1 protein expression in colorectal cancer.
AB  - We used immunohistochemical analysis to study the expression and prognostic
      impact of cyclin B1, a key molecule for G2-M phase transition during the cell
      cycle, in a series of 342 curatively resected colorectal carcinomas. In 269
      tumors (78.7%), high expression of cyclin B1 in more than 10% of tumor cells was
      observed, but there was no association between cyclin B1 expression and
      histopathologic tumor features. Univariate analysis revealed no impact on disease
      free and overall survival. Multivariate analysis revealed pT and pN categories,
      extramural blood vessel invasion, and low-grade tumor cell differentiation as
      independent prognostic predictors for overall survival, and pT and pN categories
      and tumor site for disease-free survival. According to our results, high
      expression of cyclin B1 is a frequent and early event in colorectal carcinomas.
      However, cyclin B1 expression is neither a predictor of prognosis in patients
      with colorectal cancer nor a suitable tool for identifying subgroups of patients
      at higher risk for disease recurrence.

PMID- 15487448
TI  - Usefulness of basal cell cocktail (34betaE12 + p63) in the diagnosis of atypical
      prostate glandular proliferations.
AB  - We evaluated the diagnostic usefulness of the 34betaE12-p63 cocktail, compared
      with 34betaE12 and p63 used alone, in 34 prostate needle biopsy (NBXs) and 3
      transurethral resection specimens containing atypical glandular proliferations
      and in 18 NBXs containing unequivocal prostate carcinoma (PCa). Staining
      intensity; percentage of basal cells staining in benign, atypical, and malignant
      glands; number of benign glands lacking basal cell staining; and staining
      variance were analyzed. All NBXs with unequivocal PCa were negative with all 3
      markers. Diagnoses were as follows for the atypical cases after staining for the
      3 markers: PCa, 9; postatrophic hyperplasia, 12; high-grade prostatic
      intraepithelial neoplasia (HGPIN), 5; atypical adenomatous hyperplasia, 6; benign
      atypical proliferations, 4; and HGPIN with adjacent small atypical acinar
      proliferation suggestive of PCa, 1. The cocktail demonstrated consistently strong
      staining intensity and improved basal cell staining in morphologically benign and
      benign atypical glands compared with p63 and 34betaE12 alone; it had the smallest
      staining variance compared with 34betaE12 (F < 0.0001) and p63 (F = 0.31),
      although its advantage for resolving individual atypical cases was limited
      compared with 34betaE12 and p63 alone. Of 37 atypical cases, 1 (3%) additionally
      was resolved as benign using the cocktail and p63. Because the diagnosis of PCa
      is supported by lack of basal cell staining, the immunohistochemical analysis
      with highest possible sensitivity and lowest possible variability is critical to
      ensure that a negative reaction is true. The cocktail provides a simple, cost
      effective improvement in basal cell immunohistochemical analysis of difficult
      prostate lesions.

PMID- 15487449
TI  - The use of a combination of galectin-3 and thyroid peroxidase for the diagnosis
      and prognosis of thyroid cancer.
AB  - In this retrospective histologic study, galectin-3 had a sensitivity of 92%
      (22/24) for papillary thyroid carcinoma and 44% (4/9) for follicular thyroid
      carcinoma. Thyroid peroxidase (TPO) had a sensitivity of 50% (12/24) for
      papillary and 11% (1/11) for follicular carcinoma. The combination of galectin-3
      and TPO had a sensitivity of 96% (23/24) for papillary and 44% (4/9) for
      follicular carcinoma. From a prognostic standpoint, of patients whose papillary
      carcinomas expressed both markers, all became free of disease. Of those whose
      papillary carcinomas expressed galectin-3 but not TPO, 57% (4/7) became free of
      disease, 29% (2/7) had persistent disease, and 14% (1/7) had progressive disease.
      This study confirms previous observations that galectin-3 alone is highly
      sensitive for papillary carcinoma but not adequately sensitive for follicular
      carcinoma. TPO alone is not adequately sensitive for the evaluation of any
      thyroid lesion. The combination of galectin-3 and TPO is complementary as a
      diagnostic and prognostic tool for patients with papillary carcinoma.

PMID- 15487450
TI  - Micromorphometric features of positive sentinel lymph nodes predict involvement
      of nonsentinel nodes in patients with melanoma.
AB  - The aim of the present study was to determine whether micromorphometric features
      of positive sentinel lymph nodes (SLNs) from patients with melanoma are useful
      for predicting further nodal involvement in completion lymph node dissection
      (CLND) specimens. Of 986 patients with melanoma undergoing SLN biopsy between
      March 1992 and February 2001, 175 (17.7%) had at least 1 positive SLN and 140 had
      subsequent CLND specimens available for review. Further nodal involvement in CLND
      specimens was present in 24 (17.1%) of 140 patients. Of 8 micromorphometric
      features of the SLNs that were assessed, the presence of metastases in CLND
      specimens was correlated significantly with a tumor penetrative depth (maximum
      distance of melanoma cells from the inner margin of the SLN capsule) of more than
      2 mm (P < .05), a deposit size of more than 10 mm2 (P < .01), the presence of
      melanoma cells in perinodal lymphatic vessels (P < .01), and the effacement of
      nodal architecture by metastatic melanoma cells (P < .05). Our results indicate
      that some morphologic features of melanoma metastases in SLNs predict the
      likelihood of further nodal involvement in CLND specimens.

PMID- 15487451
TI  - An investigation of the mechanisms underlying the disparity between rate of
      residual endocervical adenocarcinoma in situ (AIS) in hysterectomy specimens and
      clinical failure rate following conservatively treated AIS.
AB  - The location, amount, and anatomic relationships of adenocarcinoma in situ (AIS)
      in 5 delayed second cone biopsy excision specimens and 21 definitive-therapy
      hysterectomy specimens were measured in relation to the neosquamocolumnar
      junction (nSCJ). All 5 biopsy specimens had 1 to 2 mm of AIS situated at the
      nSCJ. None had AIS in the proximal endocervix, despite positive or extremely
      close biopsy margins. Residual AIS in hysterectomy specimens was located proximal
      to the nSCJ in 19 (90%) of 21 cases. The mean distance between AIS and the nSCJ
      was 4.9 mm in 12 (86%) of 14 hysterectomy specimens. The mean maximum length of
      AIS was 4.6 mm in hysterectomy specimens and 1.1 mm in biopsy specimens. Some
      postbiopsy failures might be de novo neoplasms that begin at the nSCJ rather than
      recrudescence of persistent AIS. Small amounts of residual AIS following cone
      biopsy excision might be eradicated by the healing process. These 2 factors might
      underlie the disparate rates of residual AIS in hysterectomy specimens and
      postbiopsy excision failures and also explain the poor correlation between biopsy
      margin status and clinical failure. Factors that impact postbiopsy AIS
      eradication might be unrelated to de novo AIS beginning at the nSCJ.

PMID- 15487452
TI  - Overrepresentation of 8q in carcinosarcomas and endometrial adenocarcinomas.
AB  - We report on genomic imbalances in 19 uterine and extrauterine carcinosarcomas
      and comparisons with findings in 7 endometrial adenocarcinomas using comparative
      genomic hybridization (CGH). In the carcinosarcomas, the number of imbalances
      ranged from 2 to 27. Overrepresentations predominated over losses (mean, 5.8 vs
      4.3) and included gains or amplifications at 8q as the single most frequent
      change in 15 of 19 carcinosarcomas, followed by overrepresentations at 3q (9/19),
      1q (7/19), 6p (7/19), and 12p (7/19). Losses were most common at 22q (9/19), 16q
      (8/19), 15q (7/19), 18q (7/19), Xp (6/19), and 9q (6/19). Among 3 carcinosarcomas
      in which carcinomatous and sarcomatous elements could be analyzed separately,
      gains of 8q were identified in both components of one tumor and in the
      sarcomatous component of another tumor. Additional CGH analyses of 7 endometrial
      adenocarcinomas revealed simpler copy number changes, including recurrent gains
      at 8q (4/7) and 1q (4/7), suggesting a central role of 8q gains in the
      pathogenesis of carcinosarcomas and endometrial adenocarcinomas.

PMID- 15487453
TI  - Immunohistochemical staining for calretinin is useful for differentiating
      schwannomas from neurofibromas.
AB  - We studied 25 cases of schwannoma and 42 cases of neurofibroma
      immunohistochemically with antibodies to calretinin and S-100 protein to explore
      the potential usefulness of calretinin in differentiating schwannomas from
      neurofibromas. Of 25 schwannomas, 24 (96%) showed moderate to strong staining for
      calretinin, with the extent of staining ranging from focal to diffuse. In
      contrast, only 3 (7%) of 42 neurofibromas displayed focal weak to moderate
      staining with calretinin. All 42 cases of neurofibromas and all 25 cases of
      schwannomas showed diffuse moderate to strong staining with S-100 protein.
      Calretinin also labeled mast cells, whose presence was confirmed further by
      staining for c-kit, which commonly was present in both tumor types in a scattered
      individual cell pattern easily differentiated from the clustered pattern of
      neoplastic spindle cells. Taken together, these results indicate that calretinin
      is detected in almost all schwannomas and in only a small percentage of
      neurofibromas, suggesting it is a useful marker for differentiating schwannomas
      from neurofibromas. Although mast cells present in these 2 neoplasms also react
      with calretinin, the pattern of staining can be distinguished easily from that of
      neoplastic cells.

PMID- 15487454
TI  - Are gastrointestinal mucosal mast cells increased in patients with systemic
      mastocytosis?
AB  - In patients with mastocytosis, gastrointestinal symptoms are a frequent
      phenomenon. However, there are only limited data about the quantity and
      distribution pattern of mast cells in the gastrointestinal mucosa. We stained
      gastroduodenal biopsy specimens from 27 patients with mastocytosis and 48 control
      subjects for mast cell tryptase, CD117, and CD25. The numbers of mucosal mast
      cells per high-power field showed wide variation in all groups and were decreased
      markedly in biopsy specimens of corpus and duodenum and statistically
      significantly decreased in antrum biopsy specimens from patients with systemic
      mastocytosis compared with patients with pure urticaria pigmentosa and with
      control subjects. Staining for tryptase showed highly significant correlation
      with staining for CD117. All mast cells were negative for CD25, which is
      expressed characteristically by neoplastic mast cells. Causes of the decrease of
      mucosal mast cells remain enigmatic, but our results show that gastrointestinal
      symptoms of patients with mastocytosis are most likely mediator-related and not
      due to an increase of local mast cells.

PMID- 15487455
TI  - Proliferating pilar tumors: a clinicopathologic study of 76 cases with a proposal
      for definition of benign and malignant variants.
AB  - We studied proliferating pilar tumors (PPTs) to establish histologic criteria
      that could predict behavior. We reviewed all cases in our consultation files
      (1989-2000) and evaluated 76 cases with meaningful follow-up information.
      Histologic examination involved attention to tumor silhouette, degree of nuclear
      atypia, mitotic activity, necrosis, and perineurial or angiolymphatic invasion.
      Tumors were stratified as follows: group 1 PPTs, circumscribed silhouettes with
      "pushing " margins, modest nuclear atypia, and an absence of pathologic mitoses,
      necrosis, and invasion of nerves or vessels; group 2 PPTs, similar to group 1 but
      manifested irregular, locally invasive silhouettes with involvement of the deep
      dermis and subcutis; group 3, invasive growth patterns, marked nuclear atypia,
      pathologic mitotic forms, and geographic necrosis, with or without involvement of
      nerves or vascular structures. Recurrence occurred in none of 48 group 1 PPTs; 3
      (15%) of 20 group 2 PPTs had local regrowth; 4 (50%) of 8 of group 3 PPTs
      recurred and/or metastasized to regional lymph nodes. The differences between
      groups 1 and 3 and between 2 and 3 were statistically significant (P = .0002, P <
      .05, respectively). It seems justifiable to regard group 1 PPTs as benign, group
      2 as having potential for locally aggressive growth, and group 3 also as having
      metastatic potential. The latter 2 categories might be equated with low and high
      grades of malignancy among PPTs of the skin.

PMID- 15487456
TI  - Women with atypical glandular cells: a long-term follow-up study in a high-risk
      population.
AB  - To determine the incidence of clinically significant lesions in high-risk
      patients with atypical glandular cells (AGCs) after 4 to 6 years of follow-up, we
      reviewed repeated Papanicolaou (Pap) test and surgical pathology results for a 3
      year period for 337 patients; 62 (18.4%) had only repeated Pap smears; 84 had Pap
      smear and histologic evaluations. In a range of repeated Pap smears from 1 to 11
      (mean, 4.2), 9 patients had persistent AGCs/atypical squamous cells; remaining
      Pap smears were judged normal. Histologic follow-up revealed a clinically
      significant lesion in 110 (40.1%) of 274 patients--low-grade squamous
      intraepithelial lesion (LSIL), 46; high-grade squamous intraepithelial lesion
      (HSIL), 47; endocervical adenocarcinoma in situ (AIS), 3; endometrial
      hyperplasia, 4; endocervical or endometrial adenocarcinoma, 10. Among patients
      with histologic follow-up, 14 lesions (12.7% of patients with clinically
      significant lesions) were diagnosed after a mean of 37 months (range, 21-59
      months): LSIL, 7; HSIL, 4; AIS, 1; endometrial adenocarcinoma, 2. Seven patients
      had negative cytologic and/or histologic evaluations between the initial
      cytologic AGC diagnosis and the final histologic diagnosis. Patients with AGCs
      are at risk of harboring clinically significant uterine lesions and should be
      followed up for a substantial period despite initial negative findings.

PMID- 15487457
TI  - ZAP-70 expression in B-cell hematologic malignancy is not limited to CLL/SLL.
AB  - ZAP-70 is a tyrosine kinase expressed in normal T cells and NK cells. Expression
      of ZAP-70 has been associated with poor prognosis in B-cell chronic lymphocytic
      leukemia and might be a surrogate marker for immunoglobin heavy chain (IGH)
      mutational status in that disease. Little is known about ZAP-70 expression in
      other hematologic malignant neoplasms. We examined 446 specimens representing a
      range of hematopoietic malignant neoplasms for ZAP-70 expression by
      immunohistochemical analysis. As expected, most T cell-lineage disorders and a
      subset of small lymphocytic lymphomas were positive. IGH mutational status
      corresponded to ZAP-70 expression in a small subset of small lymphocytic lymphoma
      cases subjected to sequence analysis. Of note, however, ZAP-70 was expressed in a
      minority of other types of B-cell lymphomas, including precursor B-cell acute
      lymphoblastic leukemia, diffuse large B-cell lymphoma, mantle cell lymphoma, and
      very rare cases of classic Hodgkin lymphoma. Immunohistochemical analysis
      represents an alternative method for assessing ZAP-70 expression and reveals that
      other B-cell malignant neoplasms express ZAP-70.

PMID- 15487458
TI  - Characterization of incidentally identified minute clonal B-lymphocyte
      populations in peripheral blood and bone marrow.
AB  - We describe 69 patients in whom small clonal B-cell populations were detected
      incidentally in blood and bone marrow samples by flow cytometric studies. In 20
      patients (29%), non-Hodgkin lymphoma (NHL) subsequently was diagnosed 0 to 40
      months (median, 0.1 month) from initial flow cytometric studies. In 49 patients
      (71%), there was no evidence of NHL after 0.5 to 72 months (median, 16 months).
      Patients without overt NHL had a higher absolute WBC count than patients with NHL
      (2,260/microL vs 1,470/microL [2.26 vs 1.47 x 10(9)/L]; P < .01). Otherwise,
      there were no clinical or hematologic differences between the 2 groups. We
      identified 70 clonal populations in the 69 patients, ranging from 0.05% to 4.5%
      (median, 1.28%) of events. The mean percentage of clonal B cells was similar for
      the 2 groups. The populations were CD5-/CD10- in 34 cases; CD5+, chronic
      lymphocytic leukemia-like in 19; CD5+, indeterminate in 9; CD10+ in 3; hairy cell
      leukemia-like in 3; and CD5+, mantle cell lymphoma-like in 2. There were no
      immunophenotypic differences in patients with and without overt NHL.

PMID- 15487459
TI  - Targeted therapies for cancer 2004.
AB  - The regulatory agency approvals in the United States and Europe of imatinib
      mesylate (Gleevec) for patients with bcr/abl-positive chronic myelogenous
      leukemia, cetuximab (Erbitux) for patients with epidermal growth factor receptor
      overexpressing metastatic colorectal cancer, the antiangiogenesis agent
      bevacizumab (Avastin), and the proteasome inhibitor bortezomib (Velcade)--and the
      considerable public interest in new anticancer drugs that take advantage of
      specific genetic defects that render the malignant cells more likely to respond
      to specific treatment--are driving a new era of integrated diagnostics and
      therapeutics. The recent discovery of a drug response predicting activating
      mutation in the epidermal growth factor receptor gene for patients with non-small
      cell lung cancer treated with gefitinib (Iressa) has intensified this interest.
      In this review, the history of targeted anticancer therapies is highlighted, with
      focus on the development of molecular diagnostics for hematologic malignancies
      and the emergence of trastuzumab (Herceptin), an antibody-based targeted therapy
      for HER-2/neu overexpressing metastatic breast cancer: The potential of
      pharmacogenomic strategies and the use of high-density genomic microarrays to
      classify and select therapy for cancer are briefly considered. This review also
      considers the widely held view that, in the next 5 to 10 years, the clinical
      application of molecular diagnostics will further revolutionize the drug
      discovery and development process; customize the selection, dosing, route of
      administration of existing and new therapeutic agents; and truly personalize
      medical care for cancer patients.

PMID- 15487461
TI  - Microwave-assisted rapid tissue processing.

PMID- 15487460
TI  - Microwave-assisted rapid tissue processing.

PMID- 15487462
TI  - Interstitial lung disease with cytomegalovirus and parvovirus B19 coinfection.

PMID- 15487465
TI  - The right thing--for the right reason.

PMID- 15487466
TI  - Clinician-assisted suicide: merciful release or unlawful death?

PMID- 15487467
TI  - Perfect peace at work?

PMID- 15487468
TI  - Thinking outside the box: rescue nurses lend a hand.

PMID- 15487469
TI  - An effective retention strategy: mentoring like Jesus.

PMID- 15487470
TI  - So what is mentoring?

PMID- 15487471
TI  - Precepting: putting myself in her shoes.

PMID- 15487473
TI  - Mobilize support groups to meet congregational needs.

PMID- 15487474
TI  - The toilet nurse.

PMID- 15487475
TI  - Maternal and child attributions in ADHD versus non-ADHD populations.
AB  - OBJECTIVE: This study explores child and maternal attributions in ADHD and non
      ADHD populations. Participants included children with ADHD (N = 26) and without
      ADHD (N = 24) and their mothers. METHOD: Children completed the Children's
      Attributional Style Questionnaire-Revised (CASQ-R; Kaslow & Nolen-Hoeksema, 1991)
      and mothers completed the Written Analogue Questionnaire (WAQ; Johnston &
      Freeman, 1997). RESULTS: Consistent with hypotheses, differences were observed
      between the ADHD and non-ADHD groups on both child and maternal attributions
      measures. Post hoc analyses in the ADHD sample indicate that maternal, but not
      child, attributions differ as a function of medication status. Finally,
      correlations between child and maternal attributions were not found to be
      statistically significant. CONCLUSION: The findings suggest that the
      attributional styles of children with ADHD may place them at risk for poor self
      esteem and/or depression in later life. The attributions provided by these
      children's mothers appear to differ slightly as a function of medication status,
      a finding that may lend insight into factors that influence parental choice of
      intervention and/or changes over the course of treatment.

PMID- 15487476
TI  - Reactive vs. proactive antisocial behavior: differential correlates of child ADHD
      symptoms?
AB  - This study examines the relation between proactive and reactive antisocial
      behavior with Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms.
      Caregivers of children aged 8 to 15 (n = 84) being evaluated at a child
      psychiatry outpatient clinic served as participants. Given the conceptual
      similarity between reactive antisocial behavior (ASB) and particular ADHD
      symptoms, we hypothesized that ADHD symptoms would be more closely related to
      reactive than to proactive ASB. Based on peer deviancy training models of ASB, we
      also hypothesized that the relation between ADHD symptoms and proactive ASB would
      increase from middle childhood to adolescence. Both hypotheses were supported.
      These findings suggest that reactive ASB is relatively specific to ADHD symptoms,
      and that intervening before early adolescence may be critical to prevent the
      onset of comorbid proactive ASB.

PMID- 15487477
TI  - The effects of yoga on the attention and behavior of boys with Attention-Deficit/
      hyperactivity Disorder (ADHD).
AB  - Boys diagnosed with ADHD by specialist pediatricians and stabilized on medication
      were randomly assigned to a 20-session yoga group (n = 11) or a control group
      (cooperative activities; n = 8). Boys were assessed pre- and post-intervention on
      the Conners' Parent and Teacher Rating Scales-Revised: Long (CPRS-R:L & CTRS-R:L;
      Conners, 1997), the Test of Variables of Attention (TOVA; Greenberg, Cormna, &
      Kindschi, 1997), and the Motion Logger Actigraph. Data were analyzed using one
      way repeated measures analysis of variance (ANOVA). Significant improvements from
      pre-test to post-test were found for the yoga, but not for the control group on
      five subscales of the Conners' Parents Rating Scales (CPRS): Oppositional, Global
      Index Emotional Lability, Global Index Total, Global Index Restless/Impulsive and
      ADHD Index. Significant improvements from pre-test to post-test were found for
      the control group, but not the yoga group on three CPRS subscales: Hyperactivity,
      Anxious/Shy, and Social Problems. Both groups improved significantly on CPRS
      Perfectionism, DSM-IV Hyperactive/ Impulsive, and DSM-IV Total. For the yoga
      group, positive change from pre- to post-test on the Conners' Teacher Rating
      Scales (CTRS) was associated with the number of sessions attended on the DSM-IV
      Hyperactive-Impulsive subscale and with a trend on DSM-IV Inattentive subscale.
      Those in the yoga group who engaged in more home practice showed a significant
      improvement on TOVA Response Time Variability with a trend on the ADHD score, and
      greater improvements on the CTRS Global Emotional Lability subscale. Results from
      the Motion Logger Actigraph were inconclusive. Although these data do not provide
      strong support for the use of yoga for ADHD, partly because the study was under
      powered, they do suggest that yoga may have merit as a complementary treatment
      for boys with ADHD already stabilized on medication, particularly for its evening
      effect when medication effects are absent. Yoga remains an investigational
      treatment, but this study supports further research into its possible uses for
      this population. These findings need to be replicated on larger groups with a
      more intensive supervised practice program.

PMID- 15487478
TI  - National trends in concomitant psychotropic medication with stimulants in
      pediatric visits: practice versus knowledge.
AB  - OBJECTIVES: (1) To examine U.S. national trends in the use of concomitant
      pharmacotherapy with the stimulant class of psychotropic drugs in youth; and (2)
      to present these trends in the context of (a) extant safety and efficacy data,
      and (b) overall trends in concomitant pharmacotherapy with psychotropic drugs for
      youth. METHODS: Prescribing data for youths under age 18 years from National
      Ambulatory Medical Surveys from 1993 to 1998 were analyzed. The visits were
      categorized into monotherapy (only one psychotropic prescribed) and concomitant
      pharmacotherapy (>1 psychotropic prescribed). The proportions of these groups
      were computed as a percentage of all visits during which a psychotropic
      medication was prescribed. Differences in proportions between surveys were
      analyzed to determine trends. RESULTS: Between 1993--94 and 1997--98, the
      proportions of visits for concomitant pharmacotherapy in association with the
      stimulant class increased nearly five-fold. This increase paralleled an overall
      increase in the proportion of visits involving prescription of more than one
      psychotropic medication among youth. CONCLUSIONS: The growth in concomitant
      pharmacotherapy with the stimulants class has out-paced the increase in
      safety/efficacy data to inform the use of this practice, resulting in a mismatch
      between trends in prescribing and growth in knowledge. A simultaneous trend of
      note is the overall increase in the use of concomitant pharmacotherapy with all
      psychotropic drugs in youth. Controlled trials are particularly needed to support
      commonly used combinations of stimulants with antidepressants in youth. In the
      absence of definitive data, clinical guidelines based on expert consensus and
      limited data are available and are useful.

PMID- 15487479
TI  - Phyllis Stern's response to Ted Greiner's letter to the editor.

PMID- 15487480
TI  - Less money less food: voices from women in urban poor families in Thailand.
AB  - Food insecurity is a public health problem. Information on how cultures perceive
      the experience of a financial crisis and resultant food insecurity is limited.
      Our purpose in this study was to understand how poor families residing in urban
      slums in Thailand perceive their food situation. Interviews were conducted with
      30 women aged 20-65 years who were household food providers. Content analysis
      revealed three themes: experiencing changes, being vulnerable to not having
      enough food, and getting support. Policy changes to address access to social and
      health services and development of additional welfare programs must be made to
      achieve food security.

PMID- 15487481
TI  - Seeking safe passage: Argentine women's perceptions of routine prenatal care.
AB  - When we were studying in Argentina, we became aware that many of the women did
      not participate in routine prenatal care. We completed descriptive qualitative
      interviews with 17 hospitalized women about their perceptions regarding prenatal
      care. Several themes arose related to the women's use of prenatal care: prenatal
      care utilization and outcomes, getting there, getting by, waiting, turning red,
      and knowing. Future research should concentrate on identifying components of
      prenatal care to build a best practice model of prenatal care that is culturally
      sensitive and personally relevant to provide safe passage for the women of
      Tucuman.

PMID- 15487482
TI  - Health care for women with children in Germany--preventive and rehabilitative
      measures for mother and child.
AB  - In Germany, the social health system tries to take into account the divergent
      expectations and needs of women with children. One of the available services for
      mentally ill women, the so called mother-child rehabilitation, is a special
      inpatient service for exhausted and depressed women. Mothers may bring their
      children along and children receive medical and psychological treatment as well
      if they need it. In the following, we describe and compare this service with
      other available services for women in Germany and draw some conclusions in regard
      to the future of these measures, taking funding problems into account.

PMID- 15487483
TI  - Toward critical research ethics: transforming ethical conduct in qualitative
      health care research.
AB  - Based on research conducted with women injection drug users (WIDUs), I discuss
      the ethical conflicts that researchers and sub-contractors face in gaining access
      to the life narratives of WIDUs. Foremost among these is the potentially
      exploitative nature of the study participant-researcher relationship. I suggest
      that federal and institutional guidelines for human subject research must
      incorporate additional safeguards to protect study populations such as WIDUs.
      Moreover, the ethical concerns related to health care research should be
      addressed in guidelines for ethical conduct with human subjects, research ethics
      seminars, and required training programs for researchers and subcontractors
      separately.

PMID- 15487484
TI  - A study of knowledge, attitude, and practice of cervical screening among female
      primary care physicians in the United Arab Emirates.
AB  - Cancer is the third leading cause of death In the United Arab Emirates (UAE),
      which is situated in the Arabian Gulf. A national programme for cervical cancer
      screening is likely to be implemented in the future. In this study, we assessed
      the knowledge, attitude, and practice of UAE female primary care physicians of
      cervical screening through a self-administered questionnaire. Of the 98
      physicians who participated in the study only 40% reported ever having performed
      a Pap smear. In the study, we identified various training needs, and a training
      programme on cervical screening currently is being developed based on the results
      of this study.

PMID- 15487485
TI  - Why do women stop smoking during pregnancy? Cigarettes taste and smell bad.
AB  - There are high rates of cigarette smoking resumption among women who have quit
      smoking while pregnant, and the reasons for this are poorly understood. Our
      purpose in this study was to obtain an in-depth description of the context
      surrounding smoking behaviors during pregnancy and the first 3 months after women
      give birth in order to gain insight into the reasons women resume smoking. We
      used a longitudinal qualitative descriptive approach with in-depth interviews
      conducted early in pregnancy, at 36 weeks of pregnancy, and 3 months postpartum.
      Our purposive sample consisted of 15 pregnant women who had stopped smoking
      without assistance by their first prenatal visit. All women smoked mentholated
      cigarettes prior to pregnancy and 40% were primiparas. A thematic content
      analysis of 43 interviews revealed that the majority of women experienced an
      aversion to the taste or smell of tobacco smoke while pregnant and attributed
      these sensation changes to being pregnant. The taste and smell of tobacco smoke
      returned to prepregnancy states postpartum, and by 3 months postpartum 73% of the
      women had resumed smoking. This physiologic change can be conceptualized as a
      pregnancy-specific motivation for smoking cessation that can inform our efforts
      toward relapse prevention.

PMID- 15487486
TI  - Improving pre- and postmenarcheal 12-year-old girls' attitudes toward
      menstruation.
AB  - Adolescence is a time of rapid changes, including risk for unwanted pregnancies
      and sexually transmitted infections. Education may improve understanding and
      attitudes toward menstruation among adolescents thus increasing their awareness
      of risks and enabling them to protect themselves accordingly. To investigate
      effects of education on attitudes, two interventions were compared in 345 12-year
      old girls. The new, active intervention given to premenarcheal girls just before
      menarche resulted in improvements in attitudes toward menstruation compared with
      standard intervention. Thus, just before menarche girls should be offered
      education modeled after the active intervention. The education must be concrete
      and based on multisensory learning.

PMID- 15487487
TI  - Task force to the rescue.

PMID- 15487488
TI  - Birth rights.

PMID- 15487489
TI  - The more you get, the longer you wait.

PMID- 15487490
TI  - As others see us.

PMID- 15487491
TI  - Nursing skills in the corridors of power.

PMID- 15487492
TI  - Plan for success.

PMID- 15487493
TI  - Rolling back the years.

PMID- 15487494
TI  - Need to be heard.

PMID- 15487495
TI  - The changing role of the healthcare assistant.
AB  - BACKGROUND: This article analyses the changes made to the role of the healthcare
      assistant (HCA) in the British healthcare system and identifies when and why
      these changes occurred. The main influences on the role of HCAs, from the time of
      Florence Nightingale through to the present day, are discussed. CONCLUSION: The
      role of the HCA has progressed from being an undervalued 'dead-end' job, to a
      skilled role that is recognised nationwide. However, the future of the HCA role
      is uncertain.

PMID- 15487496
TI  - Plagiarism: the Internet makes it easy.
AB  - This article examines the issue of plagiarism by nursing students and academics
      in British universities and highlights how electronic developments such as the
      Internet and word processing have made it easier. It describes how some websites
      support plagiarism and how, for a price, a qualification up to and including
      higher degree level may be gained without the recipient of the award having to do
      any coursework.

PMID- 15487497
TI  - Oedema: causes, physiology and nursing management.
AB  - In this article, Georgina Casey examines the underlying causes of oedema to
      enable nurses to effectively assess, care and treat patients with this condition.

PMID- 15487498
TI  - [Correction of five different types of errors of model REFSEQs appeared in NCBI
      human gene database only by using two novel human genes C17orf32 and ZNF362].
AB  - Found that there exist many mistakes in the REFSEQ issued in the genome
      annotation project of NCBI, the result of which indicates that people be cautious
      in using REFSEQ database in NCBI. By adopting the technical route combining
      bioinformatics analysis and experimental verification, through the comparison of
      the cloned genes in the non-redundant database, we found that there were many
      mistakes in the computer annotation human genome coding sequences that were
      issued on the internet. First we quoted nine wrong types of novel human genes
      anticipated by NCBI GENOME Annotation Project. Here we give one example in
      detail: (1) Comparison of the sequences between novel human gene C17orf32 and
      hypothetical human gene LOC124919. LOC123722 is a modified sequence of C17orf32
      cDNA with an inserted G between 406 -407 nucleotides. The base G in the 401
      position of LOC123722 cDNA is a redundant insert, which causes a reading frame
      shift in the translation of an alternative protein. This inserted G has not been
      found in our experimental clone, and is fully rejected by human EST alignment,
      and is shown as a redundance by genomic GT/AG organization analysis. (2)
      Comparison of the sequences between novel human gene C17orf32 and hypothetical
      human gene LOC147007. C17orf32 gene (ORF from 31 to 657 nucleotides) is located
      on human chromosome 17(Accession No. NT_010808.7), and is only linked with a
      hypothetical human gene LOC147007 (ORF from 55 to 435 nucleotides) at present.
      This hypothetical human gene sequence has not been verified by experiment, and is
      a wrong form of our verified C17orf32 gene. The full-length 1 679 bp cDNA
      sequence of C17orf32 exhibits overall homology to that of LOC147007 of 625 bp
      mRNA, with matching percentage of 37% in 36% of total window over the full-length
      nucleotide, especially 121 approximately 366 bp of LOC147007 is just the same as
      316 approximately 561 bp of C17orf32. Thus, the 126 aa protein encoded by
      XP_097165 of LOC147007 exhibits overall homology to the 208 aa protein encoded by
      C17orf32, with matching percentage of 50% in 48% of total window over the full
      length protein, especially 23 approximately 104 aa of XP_097165 is just the same
      as 96 approximately 177 aa of C17orf32 protein. Both flanking regions of
      LOC147007 outside the same ORF central part are wrong assembly of non-relative
      cDNA. In addition, we have in silico cloned a novel mouse gene, ORF32 (open
      reading frame 32) with TPA accession number of BK000258, which is the mouse
      ortholog of human C17orf32. Our strategy is helpful in both finding out more
      novel human genes and correcting the mistakes in the REFSEQs issued by NCBI
      genome annnotation project. For example, we adopted the gene anticipating method,
      through automatic calculation and analysis, anticipated two modes reference
      sequences (LOC124919 and LOC147007) from NCBI contig NT_ 010808. Both of them
      should be C17orf32, but the fact is that both of them are various wrong forms of
      C17orf32, respectively are the first type and second type of mistakes. Another
      example, we adopted gene anticipation method, through automatic calculation and
      analysis, anticipated three modes reference sequences (LOC14907, LOC200084 and
      LOC91126) from NCBI contig NT_004511 which really are one type of gene of ZNF362,
      but submitted three different wrong forms of ZNF362, respectively are: the
      fourth, fifth, and seventh type of mistakes. We can correct or avoid the
      currently wrong human genome coding sequence by using in silico clone and
      combining experimental verification. People should be cautious in treating the
      computer's annotation which may exist all type of wrong human genome coding
      sequences. The correct identification and annotation of the novel human genes
      still remain to be a long and arduous task.

PMID- 15487499
TI  - Comparative physical localization of maize mir1 gene in Zea mays L. and Coix
      lacryma-jobi L.
AB  - The maize gene mir1 encoded a cystein proteinase which is resistant to fall
      armyworm. Previously, RFLP map indicated that the mir1 was mapped on chromosome
      6. However, physical location of the mir1 gene on chromosome 6 has not been
      reported. In this study, the mir1 gene was physically located on the short arm of
      metaphase and pachytene chromosome 6 by dual-color fluorescence in situ
      hybridization (FISH) with 45S rDNA as a reference marker. The results of Southern
      blotting suggested that there were sequences homologous to mir1 in Coix lacryma
      jobi L. genome. Then, the sequences were mapped on the distal region of long arm
      of chromosome 7 in C. lacryma-jobi by FISH. The percent distance from the signal
      site to centromere was 73.33 +/- 0.15.

PMID- 15487500
TI  - [The production and multi-color genomic in situ hybridization identification of
      maize-Z. perennis substituted material].
AB  - Genus Zea. L was composed of two sections: sect. Luxuriantes Doebley & Iltis
      including Z. dipperennis, Z. luxurians and Z. perennis, and sect. Zea. mays
      consisting only one species, annual Z. mays. To improve the biodiversity of germ
      plasm in maize breeding, the study of transferring maize relatives gene into
      common maize were performed. Firstly, interspecific hybrids between maize (Zea.
      L) (2n = 20) and Z. perennis (2n = 40) were produced with the aim of transferring
      desirable horticultural traits from Z. perennis to maize. The F1 of maize x Z.
      perennis (2n = 30) plant had the most frequent configuration of 5 III + 5 II + 5
      I, which were sterile and difficult to produce progeny because of genomic
      affinities. However,few F2 individuals of maize x Z. perennis could be obtained
      by some specially treatments, and one maize-like F2 plant were obtained, which
      were used as a female parent in backcrossing with maize parent. Twelve F2 x P1 (
      BC1 F2 ) plants were obtained and then self-crossed to produce self-crossing
      generation of F2 x P1 (2n = 20) ( BC1 F3). The phenotypic characters of parents,
      F1 (2n = 30) hybrids, F2 and F2 x P1 were investigated, such as plant height,
      flowering, leaf shape and tillers. To further verify the genomic organization of
      maize-Z. perennis material, maize (inbred line 48-2) and BC1 F3 chromosomes, the
      root tip cells were analyzed by Multi-color GISH. We probed maize and BC1 F3
      chromosomes with the probe mixture containing biotin-labeled Z. perennis genomic
      DNA and digoxigenin-labeled maize genomic DNA, the maize spread exhibited 10
      chromosomes with yellow signals and the other 10 chromosomes carried green
      fluorescing bands. However, although the BC1 F3 was 2n = 20 in all cases. Multi
      color GISH images revealed that 17 chromosomes had uniform signals similar to
      maize chromosomes, but dispersed red signals over the remaining three chromosomes
      were observed, which indicated that the 3 chromosomes originated from Z.
      perennis, and they were smaller than maize chromosomes. Data obtained from multi
      color GISH images indicated that BC1 F3 was probably a substituted material from
      maize-Z. perennis.

PMID- 15487501
TI  - [Gene expression analysis of near-isogenic lines for different heterosis in
      maize].
AB  - In this report, we used three pairs of near-isogenic lines( NILs) 478,488-1 and
      488-2, which are different in seed size and leaves above the top ear, to make a
      survey of the expressions of six genes in leaf tissues of these NILs series in
      order to find whether these genes serve as models for the rate-limiting genes in
      the heterosis. Our results showed that some of genes may play a role in heterosis
      response either through increased or decreased expression. When all six genes
      were considered as a whole, they showed a tendency for higher gene expression in
      488-1 than in 488-2 and in 478, and in 488-1 x 340 than in 478 x 340 and in 488-2
      x 340. Sus1, Sh1 and ZmSps34-3' were good candidate genes because they have been
      proposed to be rate-limiting for the seed size and grain weight of the
      individuals heterosis. And also, in order to seek a molecular genetic dissection
      of heterosis, two main theories, dominance and overdominance, which hold the
      classical explanation for the heterosis, were discussed too.

PMID- 15487502
TI  - [Phylogeny of the genus Arundinaria based on nucleotide sequences of nrDNA ITS
      region].
AB  - The sequences of nrDNA regions of 17 species and Phyllostachys edulis (outgroup)
      sampled, which are of represent and type species for different taxa in the genus
      Arundinaria,were analyzed by PCR amplification and direct DNA sequencing. The
      phylogenetic trees generated from maximum parsimony analysis showed that the
      sampled bamboos were naturally monophletic, appearing that these species of the
      bamboos belong to the genus Arundinaria. The internal transcribed spacers (ITS)
      data indicated that the species were divided into two branches, one including A.
      oleosa, A. hsienchuensis, A. chino, A. amara, A. yixingensis, A. amabilis, A.
      fortunei, and A. pygmaea, the other including A. graminea, A. fargesii, A.
      faberi, A. hupehensis, Pseudosasa japonica cv. Tsutsumiana, P. japonica,
      Brachystachyum densiflorum, A. oedogonata, and A. sulcata. The result also showed
      that there was close relationship between A. graminea and A. fargesii, Pseudosasa
      japonica cv. Tsutsumiana and P. japonica, A. sulcata, Brachystachyum densiflorum
      and A. oedogonata, (99%, 100% and 82% boot-strap support respectively). Moreover,
      there was very close relationship between A. amabilis and A. hsienchuensis,
      indicating that A. amabilis belongs to the genus Arundinaria. It was shown in the
      phylogenetic tree that A. pygmaea and A. fortunei had close relationship, and
      were a sister branch to the bamboos of Pleioblastus.

PMID- 15487503
TI  - Identification of the linkage relationship between the flower colour and the
      content of erucic acid in the resynthesized Brassica napus L.
AB  - Brassica napus variety Quantum (yellow flower and low erucic content) as the
      female parent was crossed with a resynthesized Brassica napus line No. 2127-17
      (white flower and high erucic content). The segregation ratios of the flower
      colour and the erucic acid content were analyzed in the F1, BC1, F2, and DH
      (doubled haploid) populations. The results indicated that the white flower was
      dominant over yellow and the erucic acid content was additively inherited. Both
      traits fit with a monogenic inheritance model, respectively. There were strong
      evidences to support the linkage relationship between the flower colour and the
      erucic acid content in the C-genome of B. napus with a recombination frequency of
      5.8% in the DH population. The BSA (bulked segregant analysis) strategy was
      employed to identify random amplified polymorphic DNA (RAPD) marker linked to the
      genes for the flower colour and erucic acid content in the DH population. Of 685
      arbitrary 10-base pair (bp) primers, one primer S92 generated a RAPD marker S92(
      1400) that was tightly linked to the genes for the yellow flower and the low
      erucic acid content in the C-genome of B. napus L. The genetic distance of the
      genes for yellow flower and the low erucic acid content was 2.2 cM and 5.4 cM
      from the marker S92(-1400), respectively.

PMID- 15487504
TI  - [Induction and genetic analysis of laboratory mutants of Gibberella zeae
      resistance to carbendazim].
AB  - The mutants of wild-type Gibberella zeae resistance to carbendazim were generated
      in laboratory by ultra-violet (UV) irradiating and fungicide taming. Two levels
      of resistance (low, LR; high, HR) were identified among these mutants. LR mutants
      could grow at the critical concentration of 1.4 +/- microg/mL of carbendazim
      while completely inhibited above 10 microg/ mL concentration, but this phenotype
      of isolates was not detected in the field. HR mutants could grow at 100 microg/mL
      and showed negative cross-resistance with N-phenylcarbamate fungicides, such as N
      ( 3,5-dichlorophenyl) carbamate (MDPC) whereas the LR mutants were not. Moderate
      resistant (MR) mutants which could grow fast at 10 microg/mL, but completely
      inhibited at 100 microg/mL, were not generated in laboratory. HR mutants of field
      MR isolate were also generated by fungicide taming on 100 microg/mL of
      carbendazim, but these mutants did not express negative cross-resistance to MDPC.
      The genetic study suggested that the carbendazim-resistance in these mutants
      could be steadily inherited by asexual and selfed reproduction, and the
      resistance was controlled by the same single major gene both in laboratory
      mutants and field resistant isolates, the different levels of resistance or the
      same resistant level in different strains maybe conferred by mutations at
      different sites or one site with different allelic mutations. The gene
      compensates for the sensitivity to MDPC was allelic to that governs the
      carbendazim resistance, but the mutation for increasing sensitivity to MDPC in
      this gene could get the pathogen highly resistant to carbendazim.

PMID- 15487505
TI  - [Identification of a protein interacting with Shigella flexneri IpaC invasin by
      yeast two-hybrid system].
AB  - Two-hybrid system was applied to screen proteins interacting with IpaC in the
      host cell. By using two-hybrid system, the bait plasmid containing ipaC gene was
      constructed and designated pGBKT-IpaC. A human HeLa cDNA library was screened to
      isolate protein factors that might interact with IpaC. Among the 2 x 10(6) clones
      screened, 22 positive clones were picked out. Sequence analysis revealed that two
      of them contained cDNA fragments from collagenase. Subsequently the domain of
      IpaC interacting with collagenase fragment was identified. These results suggest
      that IpaC might play a role in some biological processes where collagenase is
      involved.

PMID- 15487506
TI  - [Isolation and characterization of nuclear microsatellites from Chamaecypress
      obtusa Endl].
AB  - Using 300 approximately 1 000 bp DNA fragments retrieved from 2% agarose gel
      electrophoresis on nuclear DNA samples of Chamaecypress obtusa with Nde II
      restricted digestion, microsatellites were efficiently isolated by using
      Dynabeads M280 streptavitin beads. These beads could immobilize hybrid products
      between biotin-labeled (CT) 15 probe, and 300 approximately 1 000 bp DNA
      fragments previously linkaged to Sau3A I cassette. Two enriched microsatellite
      libraries with about 2 200 positive white clones were constructed by inserting
      potential microsatellite fragments into vector pUC118 BamH I /BAP and culturing
      with host E. coli. After sequence analysis on 480 randomly picked out positive
      clones, it was revealed that the number of SSR-bearing clones accounts for 65.6%,
      and 215 clones were identified as non-homology. Furthermore,380 microsatellite
      locus were found in 215 non-homology clones indicating 1.7 loci per clone. Among
      the existed microsatellites,the expected type of (GA/CT) is the most popular
      which accounts for 86.1% and were compatible to the (CT) 15 probe, however some
      other types including (TG/AC)n and more complicated simple sequence repeats with
      3 approximately 4 bases, such as (ATAG)n, (CAGA)n, (TGA)n, (ACG)n, (TCA) n,
      (TCT)n, could be also detected in these two libraries. Finally, primers for
      amplifying 128 microsatellite locus from 114 SSR-bearing clones were designed by
      Oligo 5. 1 (http: // lxg. users4. 50megs. com/ssr. html).

PMID- 15487507
TI  - [Expression of XBP-1 in breast cancer cell lines and its role in ERalpha
      signaling].
AB  - Estrogen receptor (ERalpha) plays an important role in the development and
      progression of breast cancer. Several recent studies have demonstrated that
      expression of human X-box binding protein 1 (XBP-1) is associated with ERalpha
      status in breast tumors and overexpressed in a subset of breast tumors. XBP-1 has
      two splicing variants, which were designated as XBP-1S and XBP-1U, respectively.
      However, little is known about the expression pattern of XBP-1S and XBP-1U in
      breast cancer cells and about their roles in ERalpha signaling. In this study,
      the expression of two splicing forms of XBP-1 was detected in breast cancer cell
      lines with RT-PCR. Estrogen response element (ERE) -containing luciferase
      reporter assay was used to determine the effects of XBP-1S and XBP-1U on the
      transcription activity of ERalpha in MDA-MB-435 breast cancer cells. The result
      showed that both XBP-1S and XBP-1U enhanced the transcription activity of ERalpha
      in a hormone-independent and dose-dependent manner and the activity of of XBP-1S
      is higher than that of XBP-1U. Enhancement of ERE-containing luciferase reporter
      gene expression by XBP-1S and XBP-1U was dependent on ERalpha. These data suggest
      that XBP-1S and XBP-1U may play important roles in breast cancer growth and
      progression through ERalpha signaling.

PMID- 15487508
TI  - [Survey on native place and surname of parents in a newborn infant cord blood DNA
      bank of Han nation].
AB  - A hospital-sampled newborn infant cord blood DNA bank was collected to measure
      the homogeneity comparing with China and northern China population by
      distribution of native place and surname. The DNA bank included in 566 cases of
      newborn infant of Han nation in a hospital in Beijing to sample cord blood,
      parents' native place and surname. The parents' native place and surname were
      analyzed for distribution, proportion to evaluate their difference with those
      from China and northern China population data. In the DNA bank, native place of
      parents from Beijing was from 45.1% to 49.8%, that from Hebei, Shandong, Henan,
      Jiangsu provinces second from 3.7% to 10.6%, that from other provinces lower than
      above provinces. The native place of parents covered thirty provinces,
      municipalities and autonomous regions in China, except Tibet autonomous region
      and Guizhou province. There were 146 surnames of father and 145 surnames of
      mother included in the DNA bank. Nine surnames were found more than 1.5% in
      sampled population. The front eight surnames in order of father were Wang (9.0%),
      Li (8.0%), Zhang (7.8%), Liu (7.1%), Yang (4.1%), Chen (3.5%), Zhao (3.4%), Gao
      (1.6%). The front eight surnames in order of mother were Wang (11.8%), Li (8.3%),
      Zhang (7.8%), Liu (6.4%), Zhao (3.7%), Chen (3.4%), Sun (2.8%), Yang (2.7%). The
      front seven surnames in order of parents were Wang (10.42%), Li (8.13%), Zhang
      (7.77%), Liu (6.71%), Zhao (3.53%), Chen (3.45%), Yang (3.36%). The surname
      distribution of DNA bank was similar to that of north China (Wang 9.87%, Li
      9.28%, Zhang 9.13%, Liu 6.68%, Zhao 3.56%, Yang 3.04%, Chen 2.51%) without
      significance, chi2 = 8.54, df = 6, P = 0.20. The surname in order between DNA
      bank and northern China was uniform in front fives, the sixth and the seventh
      reversed. The newborn infant cord blood DNA bank from a hospital in Beijing
      suggests some feature of the northern China population in surnames Based on the
      hospital-sampling stratagem, to modify the sampling method might collect suitable
      newborn infant cord blood DNA bank to fit for human genetic research.

PMID- 15487509
TI  - [Screening of hypermethylated DNA fragments in tumor tissue derived from patients
      with lung cancer].
AB  - The investigations on the role of DNA methylation in carcinogenesis have been
      mainly focused on promoter hypermethylation of tumor suppressor genes. As a
      number of genes associated with cancer development may be influenced by DNA
      methylation, identification of these genes is of great importance for
      understanding the epigenetic alteration in carcinogenesis. In this study,
      hypermethylated regions of genomic DNA from Chinese lung cancer patients were
      identified by a modified methylation-sensitive arbitrarily primed PCR (MS-AP
      PCR). Eight hypermethylated DNA fragments (HMDF) were separated from a PCR
      product region between 300 and 500bp in size. After cloning, sequencing and
      searching with Blast and NewCpGseek programs,the result showed that all of them
      were typical CpG island sequences, four fragments had 99% approximately 100%
      homology to regions on human chromosome 2, 7, 9 and 10, respectively,but only one
      revealed to be known gene. Neural Network Promoter Prediction, TSSG and TSSW
      programs were run to analyze possible functions of the rest 7 fragments, of which
      4 were identified as candidate promoter regions, indicating that they might
      belong to new genes. The hypermethylated DNA fragments identified in this study
      might be specific epigenetic alterations in the Chinese lung cancer.

PMID- 15487510
TI  - Sequence analysis and phylogeny of deer (Cervidae) MtDNA control regions.
AB  - The complete control regions of three Muntiacinae species of Cervidae (M.
      reevesi, M. muntjak and M. crinifrons) were located after their complete mtDNA
      genomes were sequenced. In addition the control region sequences of nine species
      of other three Cervidae subfamilies were obtained from the Genbank. Base
      compositions, genetic distances and percent similarities among these regions were
      calculated and the homologous sequences were compared. Based on their control
      region sequences, the molecular phylogenetic tree was constructed by Neighbor
      Joining method and rooted using the mtDNA control region sequence of O. aries.
      Furthermore, the phylogenetic relationship among the twelve species was
      discussed. The lengths of their control regions ranged from 909 bp to 1 049 bp
      and A + T content is 62.06%. The sequence alignment revealed considerable
      variation in 363 nucleotide sites (about 34%). According to the phylogenetic
      tree, we suggest: (1) As a whole, the phylogenetic taxon of the twelve Cervidae
      species based on their control region sequences is consistent with that made by
      the NCBI; (2) A. alces, a species of Alces (subfamily: Odocoileinae) is most
      antique one among the twelve Cervidae species; (3) M. reevesi is more antique
      than M. muntjak and M. crinifrons; (4) H. inermis, belonging to the subfamily
      Hydropotinae, is merged into the branch which includes C. capreolus and C.
      pygargus, two species of Capreolus (subfamily: Odocoileinae).

PMID- 15487511
TI  - [Cloning and analysis of NADP(H) -dependent retinol dehydrogenase/reductase gene:
      a novel member of short-chain dehydrogenase/reductase].
AB  - The total RNA was purified from bovine liver. According to the cDNA sequences of
      human, mouse and rabbit NADP(H)-dependent retinol dehydrogenase/reductase (NRDR)
      gene, the gene-specific primers were designed and synthesized. In this study, we
      cloned the full-length cDNA of bovine liver NRDR by rapid amplification of cDNA
      ends (RACE) and RT-PCR methods. The bovine NRDR cDNA is 1 266 bp and the ORF,
      like other NRDR cDNAs, is 783 bp, encoding 260 amino acid residues. The bovine
      NRDR exhibited the identity in amino acid sequence to those of human, mouse and
      rabbit NRDR. It contains short-chain dehydrogenase/reductase (SDR) conservative
      motif and the peroxisomal targeting singal (PTS1) sequence at their C-terminal.
      In conclusion, the bovine NRDR cDNA was successfully cloned with RACE methods and
      submitted to GenBank(AF487454), whose nucleotide sequence and the deduced amino
      acid sequence were analyzed with Bioinformatics, that belongs to a novel
      peroxisomal SDR superfamily and plays an important role in the rate-limiting step
      of synthesizing retinoic acid. This is the first report suggesting the SDR
      participation of mammalian peroxisomers in retinoid metabolism and it provides a
      reliable foundation to further investigate the biological function of this
      protein and retinoic acid biosynthesis.

PMID- 15487512
TI  - [Compariative study of mitochondrial tRNA gene sequence and secondary structure
      among fifteen Predatory birds].
AB  - Three major clusters of mitochondrial tRNA genes (tRNA(Ile) -tRNA(Gln) 
      tRNA(Met), tRNA(Trp)- tRNA(Ala) -tRNA(Asn)- tRNA(CYs) -tRNA(Tyr) and tRNA(His)
      tRNA(Ser)(AGY) -tRNA(Leu)(CUN) from 13 species of Predatory birds were amplified
      and sequenced. The length of these tRNA clusters was similar among species (212
      approximately 214 bp, 353 approximately 362 bp, 205 approximately 208 bp,
      respectively), and 47% of the sequences were variable, 67% of which were involved
      in the loop regions. The stem regions were relatively conserved, and the variable
      base pairs were under the restriction of compensatory changes or G-U wobble
      pairing which could be regarded as mechanisms for maintaining a stable secondary
      structure. Maximum-parsimony (MP) and Neighbor joining (NJ) phylogenetic trees
      were constructed using all the tRNA gene sequences or stein-forming nucleotides
      with Caprimulgus indicus as outgroup. We found that the bootstrap values for
      branches of trees using the tRNA sequences were commonly higher than the others,
      therefore the phylogenetic relationship of Predatory birds reflected by these
      data may be closer to the truth. Phylogenetic analyses indicated that
      Accipitridae was closer to Strigidae instead of Falconidae, and the
      classification of Tytonidae was different from the conclusion from the previously
      morphological and DNA-DNA hybridization studies. By comparing the secondary
      structure among taxa we found that the characters of nucleotide insertions and
      deletions in some tRNA genes have synapomorphies, suggesting that these
      characters may be useful for resolving the phylogenetic relationship of different
      families in Predatory birds with higher phylogenetic performance.

PMID- 15487513
TI  - [Progress in nuclear receptor research].
AB  - Nuclear receptors belong to a superfamily of ligand-activated transcription
      factors, which are involved in regulating gene expression in development, cell
      differentiation, physiological and metabolic processes. In this review we
      summarize the studies of nuclear receptor and present the progresses in the
      researches on nuclear receptor and lipid physiology, nuclear receptor and tumor,
      and nuclear receptor and co-regulators.

PMID- 15487514
TI  - [Ex utero intrapartum treatment. A new therapeutic possibility for children with
      congenital airway obstruction].

PMID- 15487515
TI  - [Specific developmental disorders in children].

PMID- 15487516
TI  - [Children with developmental coordination disorder. A review].

PMID- 15487517
TI  - [Ex utero intrapartum treatment procedures in prenatally diagnosed airway
      obstruction].

PMID- 15487518
TI  - [Lipogenesis: does it have a relevance in the obesity research?].

PMID- 15487519
TI  - [Fibrin sealants can reduce the use of blood transfusions in surgery. A status
      article based on the Cochrane analysis "Fibrin sealant use for minimising peri
      operative blood transfusion"].

PMID- 15487520
TI  - [Mortality among children of childhood cancer survivors. A population-based
      cohort study].

PMID- 15487521
TI  - [Cervical operation using Cloward's method. A study of the effects and prognostic
      factors in first-time surgical patients].

PMID- 15487522
TI  - [Use of aminoglycosides in Danish intensive care units].

PMID- 15487523
TI  - [Occurrence of recurrent paralysis among cases referred for speech-phoniatric
      investigation at the county of Viborg during a 5-year period].

PMID- 15487524
TI  - [An accelerated recovery program following Cesarean section].

PMID- 15487525
TI  - [Should obese patients follow a low-glycemic index diet?].

PMID- 15487526
TI  - [Intraabdominal obesity and metabolic risk factors].

PMID- 15487527
TI  - [Ex utero intrapartum treatment procedure in prenatally diagnosed neck mass. The
      first two treatments in Denmark].

PMID- 15487528
TI  - [Febrile convulsions: at the emergency room].

PMID- 15487529
TI  - [Allergic contact dermatitis after hair dyeing].

PMID- 15487530
TI  - [Pneumatosis intestinalis in children].

PMID- 15487531
TI  - [Generic preparations and name confusion].

PMID- 15487532
TI  - [Thirty years with the production of "wrong inlays"].

PMID- 15487533
TI  - [Medical latin].

PMID- 15487534
TI  - [Congress participation].

PMID- 15487535
TI  - A healthy imagination? Editorial for the special issue of memory: mental imagery
      and memory in psychopathology.

PMID- 15487536
TI  - Reflecting on imagery: a clinical perspective and overview of the special issue
      of memory on mental imagery and memory in psychopathology.
AB  - The authors provide an overview of the papers in the special issue of Memory on
      mental imagery and memory in psychopathology. The papers address emotional,
      intrusive mental imagery across a range of psychological disorders including post
      traumatic stress disorder (PTSD), agoraphobia, body dysmorphic disorder, mood
      disorders, and psychosis. They include work on information processing issues
      including modelling cravings, conditioning, and aversions, as well as imagery
      qualities such as vividness and emotionality. The overview aims to place the
      articles in a broader context and draw out some exciting implications of this
      novel work. It provides a clinical context to the recent growth in this area from
      a cognitive behavioural therapy (CBT) perspective. We begin with PTSD, and
      consider links to imagery in other disorders. The clinical implications stemming
      from this empirical work and from autobiographical memory theory are discussed.
      These include consideration of a variety of techniques for eliminating
      troublesome imagery, and creating healthy, realistic alternatives.

PMID- 15487537
TI  - Intrusive re-experiencing in post-traumatic stress disorder: phenomenology,
      theory, and therapy.
AB  - The article describes features of trauma memories in post-traumatic stress
      disorder (PTSD), including characteristics of unintentional re-experiencing
      symptoms and intentional recall of trauma narratives. Reexperiencing symptoms are
      usually sensory impressions and emotional responses from the trauma that appear
      to lack a time perspective and a context. The vast majority of intrusive memories
      can be interpreted as re-experiencing of warning signals, i.e., stimuli that
      signalled the onset of the trauma or of moments when the meaning of the event
      changed for the worse. Triggers of re-experiencing symptoms include stimuli that
      have perceptual similarity to cues accompanying the traumatic event. Intentional
      recall of the trauma in PTSD may be characterised by confusion about temporal
      order, and difficulty in accessing important details, both of which contribute to
      problematic appraisals. Recall tends to be disjointed. When patients with PTSD
      deliberately recall the worst moments of the trauma, they often do not access
      other relevant (usually subsequent) information that would correct
      impressions/predictions made at the time. A theoretical analysis of re
      experiencing symptoms and their triggers is offered, and implications for
      treatment are discussed. These include the need to actively incorporate updating
      information ("I know now ...") into the worst moments of the trauma memory, and
      to train patients to discriminate between the stimuli that were present during
      the trauma ("then") and the innocuous triggers of re-experiencing symptoms
      ("now").

PMID- 15487538
TI  - Occurrence of imagery and its link with early memories in agoraphobia.
AB  - Recent cognitive models suggest that mental imagery can help us understand the
      maintenance of anxiety disorders (e.g., de Silva, 1986; Hackmann, Surawy, &
      Clark, 1998). However, imagery is relatively unexplored within agoraphobia. Such
      images are also thought to be useful in uncovering memories that occurred around
      the onset of a disorder (Hackmann, Clark, & McManus, 2000). A total of 20
      patients with agoraphobia and 20 matched controls took part in this
      investigation. Participants described any recurrent images they experienced in
      agoraphobic situations, and also any associated memories. All patients with
      agoraphobia (but no control participants) reported having distinct recurrent
      images in "agoraphobic situations". Most images involved several sensory
      modalities and in the majority of cases appeared to be linked with unpleasant
      memories of events experienced many years previously. While these exploratory
      findings require replication, potential treatment implications are discussed.

PMID- 15487539
TI  - Spontaneously occurring images and early memories in people with body dysmorphic
      disorder.
AB  - A semi-structured interview assessing the presence and characteristics of
      spontaneous appearance-related images was designed and administered. A total of
      18 patients with body dysmorphic disorder (BDD) and 18 normal controls took part.
      The BDD patients were found to have spontaneously occurring appearance-related
      images that were significantly more negative, recurrent, and viewed from an
      observer perspective than control participants. These images were more vivid and
      detailed and typically involved visual and organic (internal body) sensations.
      The study also found that BDD images were linked to early stressful memories, and
      that images were more likely than verbal thoughts to be linked to these memories.
      Implications for theory and clinical practice are discussed.

PMID- 15487540
TI  - A preliminary study of autobiographical memory in remitted bipolar and unipolar
      depression and the role of imagery in the specificity of memory.
AB  - Autobiographical memory was investigated in a sample of 19 individuals with
      remitted bipolar affective disorder and a community sample of 16 individuals with
      remitted unipolar depression who had similar low levels of current symptoms. Each
      participant was prompted to recall one positive memory and one negative memory,
      to rate it on several scales, and to describe it in detail. Relative to the
      remitted unipolar group, the remitted bipolar group reported more general than
      specific negative memories and more frequent recollections of the negative memory
      during their everyday life. Across the sample, 95% of all specific memories
      involved a mental image, whereas only 56% of all general memories involved a
      mental image, suggesting a role of imagery in the retrieval of a specific memory.
      Characteristic examples of memories are provided. These results are preliminary
      yet they suggest that patients with bipolar disorder in remission may show memory
      characteristics that are often associated with symptomatic unipolar depression.

PMID- 15487541
TI  - Individual differences in imagery and reports of aversions.
AB  - Recent theoretical models highlighting the role of imagery in trauma and aversion
      learning focus on the role of images in memory (e.g., Brewin, Dalgleish, &
      Joseph, 1996) and images as substitute stimuli in aversive conditioning (Dadds,
      Bovbjerg, Redd, & Cutmore, 1997). An unanswered question is whether individual
      differences in imagery are associated with different rates of traumatisation and
      aversion states (fear and avoidance of various stimuli). We examine one aspect of
      this: does high imagery ability correlate with the frequency with which people
      report aversions? Three samples of university students were tested on the Betts
      Questionnaire Upon Mental Imagery, the Tellegen Absorption Scale, and a new
      measure we designed to sample of range of aversions. As hypothesised, vividness
      of imagery showed positive correlations with number of aversions reported. This
      relationship held after controlling for general neuroticism and proneness to
      disgust. Results for absorption showed no relationship. The results are unable to
      disentangle causal paths but suggest a focus on individual differences in imagery
      vividness may be fruitful for understanding individual differences in aversion
      learning.

PMID- 15487542
TI  - Intrusive and non-intrusive memories in a non-clinical sample: the effects of
      mood and affect on imagery vividness.
AB  - We studied the number, valence, and vividness of intrusive and non-intrusive
      memories in two groups (N = 20) of pre-screened non-depressed mood and depressed
      mood undergraduate participants. They were asked to generate as many intrusive
      memories (IMs) as possible from the prior 2 weeks, together with pleasant and
      unpleasant non-intrusive memories from the same period. They subsequently formed
      images of these memories and rated them on measures of vividness, valence,
      arousal, and overall affect, while having their heart rate, skin conductance, and
      electromyogram monitored. IMs were common, with participants generating a mean of
      1.15 pleasant IMs and 1.60 unpleasant IMs, and there was some evidence that they
      were mood-congruent. IMs were more vivid than non-intrusive memories, a
      difference not due to either valence or arousal. We conclude that IMs are a
      general feature of human memory rather than just a symptom of certain clinical
      disorders.

PMID- 15487543
TI  - Determinants of the vividness of visual imagery: the effects of delayed recall,
      stimulus affect and individual differences.
AB  - This study investigated the influence of emotion on vividness of imagery. A total
      of 80 undergraduate participants saw 25 pictures from the International Affective
      Picture System, representing different dimensions of valence and arousal. They
      rated each stimulus for valence, arousal, and emotionality. Each stimulus was
      then presented again, and participants formed an image of it, rating the image
      for vividness, valence, arousal, and emotionality. During a 15-minute retention
      interval, participants completed several individual differences questionnaires.
      They then recalled each image from a verbal prompt and re-rated its quality.
      Slides rated as extremely valenced and highly arousing were more vividly imaged
      than neutral slides. Low mood was also associated with more vivid imagery. The
      influence of stimulus variables was greater in the immediate imagery phase; that
      of individual differences tended to be greater in the delayed imagery phase. Of
      29 participants, 7 reported intrusive memories of highly unpleasant stimuli at 1
      year follow-up.

PMID- 15487544
TI  - Memory perspective and self-concept in social anxiety: an exploratory study.
AB  - The mental representation of self and observer perspective images are important
      maintaining factors in cognitive models of social phobia (Clark & Wells, 1995;
      Rapee & Heimberg, 1997). This study investigates Libby and Eibach's (2002)
      hypothesis that the observer perspective is used to recall memories that are
      incongruent with current self-concept. A total of 60 participants (divided into
      high and low social anxiety groups) completed a questionnaire in which they
      described current self-concept, recalled four memories of social occasions (two
      congruent, two incongruent), and rated memory age and vividness. Congruence was
      defined as memories that "fit" with current self-descriptions. A qualitative
      analysis of self-concept showed that both groups used a similar range of themes.
      High socially anxious participants recalled more observer perspective memories in
      the second incongruent memory. Congruence did not influence vividness, but public
      self-consciousness did. The implications of the results are discussed and
      suggestions made for future research.

PMID- 15487545
TI  - Negative self-imagery in social anxiety contaminates social interactions.
AB  - Patients with social phobia report experiencing negative images of themselves
      performing poorly when in feared social situations. The present study
      investigates whether such negative self-imagery (based on memory of past social
      situations) contaminates social interactions. High socially anxious volunteers
      participated in two conversations with another volunteer (conversational
      partner). During one conversation, the socially anxious volunteers held in mind a
      negative self-image, and during the other they held in mind a less negative
      (control) self-image. As predicted, when holding the negative image the socially
      anxious volunteers felt more anxious, reported using more safety behaviours,
      believed that they performed more poorly, and showed greater overestimation of
      how poorly they came across (relative to ratings by the conversational partner).
      Conversational partners rated the socially anxious volunteers' performance as
      poorer in the negative image condition. Furthermore, the conversation was
      contaminated since both groups of participants rated its quality as poorer in the
      negative image condition.

PMID- 15487546
TI  - A pilot exploration of the use of compassionate images in a group of self
      critical people.
AB  - Self-criticism has long been associated with a variety of psychological problems
      and is often a key focus for intervention in psychotherapy. Recent work has
      suggested that self-critics have underelaborated and underdeveloped capacities
      for compassionate self-soothing and warmth. This pilot study developed a diary
      for monitoring self-attacking and self-soothing thoughts and images. It also
      explored the personal experiences of a group of volunteer self-critics from the
      local depression support group who were given training in self-soothing and self
      compassion. Although using small numbers, this study suggests the potential value
      of developing more complex methodologies for studying the capacity for self
      compassion, interventions to increase self-compassion (including imagery
      techniques), and their effects on mental health.

PMID- 15487547
TI  - The use of imagery in cognitive therapy for psychosis: a case example.
AB  - There has been a long tradition of studying imagery in relation to psychotic
      symptoms. Recent studies have suggested that imagery may be involved in the
      development and maintenance of psychotic symptoms (hallucinations and delusions
      in particular). Following a review of this literature, including work conducted
      by the author and colleagues, a case study is used to illustrate the clinical
      applications of this work. Working with images that were associated with
      persecutory delusions appeared to contribute to a reduction in distress,
      preoccupation, and conviction in relation to these beliefs, which were assessed
      using a standardised measure (PSYRATS). The implications for theory, practice,
      and future research are considered.

PMID- 15487548
TI  - Images and goals.
AB  - We propose that mental images are derived from goals. Goals are represented in a
      complex hierarchy and form a major part of the "working self". Images reflect the
      existence of specific goals and also act to maintain goals by facilitating the
      derivation of beliefs from the content of an image. Images in psychopathology may
      reflect the operation of dysfunctional goals: goals that are unconstrained and
      which increase discrepancy (experienced as anxiety) within the goal system.
      Another feature of the goal system is that it is conservative and avoids change.
      By this view some aspects of distortions in intrusive images of traumatic
      experiences might be viewed as a defence against goal change. Conversely
      generating new images might lead to the formation of new goals. These ideas are
      applied to the findings of the papers in this special issue of Memory and to
      several new case studies.

PMID- 15487549
TI  - Induction of type-X collagen gene transcription by retinoids occurs in part
      through the BMP-signaling pathway.

PMID- 15487550
TI  - Electrogustometric thresholds: relationship to anterior tongue locus, area of
      stimulation, and number of fungiform papillae.
AB  - It is well established that, on the anterior tongue, thresholds for chemical
      tastants are inversely related to the number of fungiform papillae. However, it
      is not known whether this is the case for thresholds for electrical currents
      presented to the lingual surface. In this study, electrical thresholds for 16
      subjects were determined at four left-side anterior lingual locations: tongue tip
      (TT), a region 1.7 cm posterior to the TT, a region 3.4 cm posterior to the TT,
      and a region 1.7 cm from the TT along the lateral margin. Two electrode sizes
      (12.5 mm2 and 50 mm2) were employed for the anodal current, and stimulus duration
      was held constant at 0.5 s. The number of fungiform papillae was determined using
      videomicroscopy. Analogous to what is seen with chemical stimulation, an inverse
      relationship was present between the mean electrical thresholds, expressed in
      terms of current density, and the number of papillae within the stimulated
      regions. The TT-which has the highest density of fungiform papillae--was found to
      be more sensitive than the other tongue regions evaluated. Also paralleling
      chemical thresholds, the mean electrical threshold values were lower (i.e.,
      sensitivity was higher) at a given tongue locus for the 50-mm2 than for the 12.5
      mm2 stimulus area. Overall, this study demonstrates that thresholds for
      electrical stimulation vary across discrete regions of the anterior tongue and
      are specifically related to the number of fungiform papillae within the
      stimulated regions. These observations provide additional support for the
      hypothesis that lingual sensations induced by low levels of electrical current
      are mediated by the taste system.

PMID- 15487551
TI  - Regulation of inflammatory responses.
AB  - Leukocytes play an important role in host defense and inflammatory disease. The
      effects of leukocytes are mediated by bacterial peptide, n-formyl-Met-Leu-Phe
      (fMLP), which interacts with a G protein-related kinase receptor to produce acute
      (degranulation) and chronic (chemokine production) inflammatory mediators. The
      purpose of this study was to determine the role of fMLP receptor phosphorylation
      by G protein-related kinase, GRK2, on degranulation and chemokine production.
      Here we show over-expression of GRK2 decreases degranulation and increases
      chemokine production. These studies suggest that receptor phosphorylation plays a
      unique role in "turning off" acute inflammation and simultaneously "turning on" a
      chronic inflammatory response. This study has relevance to many inflammatory
      diseases, including many in the oral cavity.

PMID- 15487552
TI  - Radiographic assessment of alveolar bone loss.

PMID- 15487553
TI  - Superimposition of serial cephalometric images directly on a computer monitor.

PMID- 15487554
TI  - Identification of anti-HIV components of salivary agglutinin (SAG).

PMID- 15487555
TI  - Is there a dentist in the House...of Representatives?

PMID- 15487556
TI  - Alumni profile: century man.

PMID- 15487557
TI  - CMS posts comparison prices for popular drug classes.

PMID- 15487558
TI  - Perspectives. Specialty-hospital fight to return with vengeance in 2005.

PMID- 15487560
TI  - Job-based premiums rise by double digits...again.

PMID- 15487559
TI  - CMS rules on employers, formularies, PPOs raise concerns.

PMID- 15487561
TI  - Magnetic resonance imaging of articular process joint geometry and intervertebral
      disk degeneration in the caudal lumbar spine (L5-S1) of dogs with clinical signs
      of cauda equina compression.
AB  - The geometry of the lumbosacral region has been suspected to play a role in the
      development of degenerative lumbosacral stenosis in the dog. In this study, 50
      dogs (21 German Shepherd dogs and 29 dogs of other breeds) with clinical signs of
      cauda equina compression were studied by magnetic resonance (MR) imaging. The
      orientation of the articular process joints in the L5-S1 region and the angle
      difference between two adjacent motion segments were calculated. Intervertebral
      disc degeneration of the same region was identified and classified in four
      stages. A positive association between MR-imaging stage and articular process
      joint angle difference in the transverse plane was found in the two groups of
      animals. German Shepherd dogs and dogs of other breeds had different geometry of
      the lumbosacral region with different articular process joint angles in the
      transverse plane and statistically different stages of disc degeneration.

PMID- 15487562
TI  - Computed tomographic features of suspected traumatic injury to the iliopsoas and
      pelvic limb musculature of a dog.
AB  - Computed-tomographic (CT) findings in a dog with acute suspected traumatic injury
      to the iliopsoas and neighboring pelvic musculature include enlargement of the
      affected muscles, multifocal intramuscular hypoattenuating areas, and nonuniform
      contrast enhancement of injured musculature. The CT features are postulated to be
      the result of intramuscular edema and inflammation, and correspond well to
      previously described ultrasonographic findings in dogs. Because of the close
      anatomic association between the femoral nerve and iliopsoas muscle, dogs with
      suspected iliopsoas injuries should be carefully evaluated for evidence of
      femoral nerve dysfunction. CT imaging may provide useful information regarding
      the nature and extent of iliopsoas muscular damage, as well as concurrent
      injuries in the actuely traumatized patient.

PMID- 15487563
TI  - Low-field magnetic resonance imaging of bone marrow in the lumbar spine, pelvis,
      and femur in the adult dog.
AB  - The purpose of this study was to describe the appearance of normal bone marrow in
      seven adult dogs using low-field (0.3T) magnetic resonance (MR) imaging. The
      areas imaged included the lumbar spine, pelvis, and femur. T1-weighted, fast spin
      echo T2-weighted, and short tau (T1) inversion recovery (STIR) sequences were
      obtained at all locations. Histopathology was performed on sections from the
      sixth lumbar vertebral body, the wing of the ilium, and the femur (head and neck,
      mid-diaphysis, and condyle) for evaluation of cellularity and fat content. The
      lumbar spine and pelvic marrow MR images were similar in all dogs. The lumbar
      vertebral bone marrow was uniform, intermediate signal intensity, and isointense
      to muscle on all sequences. There was variation between dogs in the bone marrow
      distribution with MR imaging of the femur. In the proximal and mid-diaphysis of
      the femur there was patchy high-signal intensity on T1- and T2-weighted images,
      and hypointense foci on the STIR images. The distal femoral metaphysis had a
      variable pattern ranging from intermediate-to-high signal on T1- and T2-weighted
      images and intermediate-to-low signal on STIR images. The femoral condyles were
      uniformly high signal on T1- and T2-weighted images and hypointense on STIR
      images. Histopathologically there was a normal variation in the bone marrow
      cellularity. The marrow was normocellular (25-75% cellularity) for all sites
      examined except the femoral condyles, which were hypocellular (<25% cellularity).

PMID- 15487564
TI  - Computed tomographic arthrography of the normal canine stifle.
AB  - Computed tomographic (CT) imaging of eight normal cadaveric canine stifles was
      performed before and after intra-articular administration of iodinated contrast
      medium. Transverse CT images were reconstructed in dorsal, parasagittal, and
      oblique planes. The following ligamentous structures were identified on
      transverse CT images in all stifles: cranial cruciate ligament, caudal cruciate
      ligament, medial meniscus, lateral meniscus, and the medial and lateral
      collateral ligaments. The following ligamentous structures were identified on
      transverse computed tomographic arthrography (CTA) images in all stifles: cranial
      cruciate ligament, caudal cruciate ligament, medial meniscus, lateral meniscus,
      meniscofemoral ligament, cranial meniscotibial ligaments, caudal meniscotibial
      ligaments, intermeniscal (transverse) ligament, and the medial and lateral
      collateral ligaments. The patellar tendon was identified on transverse and
      reconstructed dorsal and sagittal CT and CTA images in all stifles. Multiplanar
      reconstructions enabled further evaluation of the continuity of the cranial and
      caudal cruciate ligaments and menisci. The medial and lateral collateral
      ligaments were not clearly identified on CT or CTA multiplanar reconstructed
      images.

PMID- 15487565
TI  - Stress fracture of the scapula in two horses.
AB  - Stress fracture of the scapula in two horses is described. Both horses had a
      history of acute lameness after strenuous exercise. Using elective nuclear
      scintigraphy focal increased radiopharmaceutical uptake in the affected scapula
      consistent with a fracture was identified. Standing radiography was nondiagnostic
      in both horses. Ultrasonographic findings in one horse were consistent with a
      minimally displaced incomplete fracture. Both horses were treated conservatively
      and returned to train and race successfully postinjury. Veterinary

PMID- 15487566
TI  - Radiographic, ultrasonographic, and computed tomographic appearance of alveolar
      echinococcosis in dogs.
AB  - Alveolar echinococcosis is a rare metacestodal infection of humans and domestic
      animals with Echinococcus multilocularis and predominantly affects the liver. In
      humans, diagnosis is based on serology, ultrasonography, computed tomography
      (CT), and magnetic resonance imaging (MRI), techniques that have not yet been
      validated for the diagnosis of alveolar echinococcosis in dogs. Therefore, the
      purpose of this retrospective study was to describe the radiographic,
      ultrasonographic, and CT appearance of canine alveolar echinococcosis. Eleven
      dogs with confirmed alveolar echinococcosis (PCR or histology from biopsy
      material of metacestode tissue) diagnosed between 1995 and 2003 were included in
      the study. The age of the dogs at initial presentation ranged from 7 months to
      10.5 years. Abdominal radiographs were made in nine animals, abdominal
      ultrasonography was performed in 10 dogs, and two CT studies in one dog,
      respectively. The history, clinical presentation, and laboratory findings for the
      11 dogs were unspecific, the most frequent clinical finding being nonpainful
      progressive abdominal distention. All radiographed dogs had large liver masses;
      they contained small mineralizations in five. The most frequent ultrasonographic
      finding was multiple large cavitary masses with or without wall mineralizations.
      Seven animals received surgical and subsequent medical therapy with albendazole
      (10mg/kg) and all went into clinical remission. This study reviewed for the first
      time imaging findings associated with alveolar echinococcosis. The disease has to
      be included in the list of differential diagnoses in dogs with large, cavitary
      liver masses, particularly when mineralization is noted.

PMID- 15487567
TI  - Clarifying some aspects of diagnostic-accuracy research.
AB  - Evidence-based medicine is an approach to improved patient care that integrates
      clinical experience with basic science and clinical research in diagnostic
      accuracy, prognostic indicators, efficacy, and safety of treatments. Both
      clinical experience and methodical research assessments are essential components
      in this type of medical practice and underscore the importance of providing
      residents the opportunity to gain clinical experience as well as training them in
      how to perform, apply, and interpret clinical research in diagnostic imaging. The
      challenge for researchers is to design a study so that the data are valid and may
      be generalized to clinical situations where the test will be used. When assisting
      residents in the design of a research project for accuracy assessment of an
      imaging test, we consistently have observed three problem areas that if
      uncorrected would preclude the study results from being generalized to clinical
      situations where the test will be used: (1) understanding what is being measured,
      (2) appropriate selection of the sample population, and (3) the impact of the
      variability of the decision criterion. In this paper, we review these issues and
      suggest some solutions.

PMID- 15487568
TI  - Ultrasonographic diagnosis of portosystemic shunting in dogs and cats.
AB  - The value of ultrasonography was evaluated in 85 dogs and 17 cats presented with
      a clinically suspected portosystemic shunt (PSS). A PSS was confirmed in 50 dogs
      and nine cats (single congenital extrahepatic in 42, single congenital
      intrahepatic in 11, and multiple acquired in six). Six dogs and one cat had
      hepatic microvascular dysplasia, and 29 dogs and seven cats had a normal portal
      system. Ultrasonography was 92% sensitive, 98% specific, and had positive and
      negative predictive values of 98% and 89%, respectively, in identifying PSS, with
      an overall accuracy of 95%. When a PSS was identified with ultrasonography,
      extrahepatic, intrahepatic, and multiple acquired PSS could be correctly
      differentiated in 53/54 patients (98%). The combination of a small liver, large
      kidneys, and uroliths had positive and negative predictive values of 100% and 51%
      for the presence of a congenital PSS in dogs. The portal vein/aorta (PV/Ao) and
      portal vein/caudal vena cava (PV/ CVC) ratios were smaller in animals with
      extrahepatic PSSs compared with animals with microvascular dysplasia,
      intrahepatic PSSs and those without portal venous anomalies (P<0.001). All dogs
      and cats with a PV/Ao ratio of < or = 0.65 had an extrahepatic PSS or idiopathic
      noncirrhotic portal hypertension. Dogs and cats with PV/Ao and PV/CVC ratios of >
      or = 0.8 and > or = 0.75, respectively, did not have an extrahepatic PSS. Reduced
      or reversed portal flow was seen in four of four patients with multiple acquired
      PSSs secondary to portal hypertension. The presence of turbulence in the caudal
      vena cava of dogs had positive and negative predictive values of 91% and 84%,
      respectively, for the presence of any PSS terminating into that vein.

PMID- 15487569
TI  - A review of the sonographic assessment of tumor metastases in liver and
      superficial lymph nodes.
AB  - Diagnostic imaging techniques are an important part of the diagnostic workup and
      staging of cancer patients. Ultrasound is of particular interest in this respect.
      In so far as tumor metastases are concerned, ultrasonography of regional lymph
      nodes and of the liver can provide valuable information. In humans many criteria,
      some of them objective, have been evaluated as indicators of malignancy. The most
      diagnostically helpful of these include the short/long axis ratio of the lymph
      node, the pattern of distribution of the blood vessels within the lymph node, and
      to some extent the calculated values for resistive and pulsatility indices.
      Putative objective criteria to improve the specificity of ultrasound for
      metastases detection in the liver have also been evaluated. These include
      perfusion indices, primarily using analysis of Doppler frequencies (Doppler
      perfusion index) and hepatic venography using an ultrasound contrast agent.
      Contrast-enhanced ultrasonography is a new and promising area to help the initial
      diagnosis and characterization of malignancy, particularly for focal lesions in
      the liver. This review discusses the use of ultrasound for detection of
      metastases and presents material from four veterinary cases.

PMID- 15487570
TI  - Ultrasonography of the solar aspect of the distal phalanx in the horse.
AB  - Ultrasonographic examinations were performed on the solar aspect of the distal
      phalanx of 10 feet of five normal live horses (Group 1), 22 feet of seven normal
      cadavers (Group 2), and nine feet of five horses with pathology of the dorsal
      solar aspect of the distal phalanx (Group 3). Lateromedial radiographs of the
      distal phalanx were made in all groups, and in Group 2, digits were sagitally
      sectioned after imaging. The ultrasonographic and radiographic appearance of the
      sagittal solar aspect of the distal phalanx was described. Measurements of the
      distance between the sole and the distal tip of the distal phalanx (A), the solar
      aspect of the apex of the frog and the distal phalanx (B), and the body of the
      frog's surface and flexor surface of the distal sesamoid bone (C) were made
      ultrasonographically, radiographically, and on the sectioned cadaver specimens.
      There was no statistical difference between the radiographic, ultrasonographic,
      and direct cadaver measurements in A and C. In B, there was a statistical
      difference between the radiographic, ultrasonographic, and cadaver measurements
      most likely as a result of the difference in trimming of the frog apex.
      Ultrasonographic and radiographic examination of the nine feet of the five horses
      in Group 3 were performed and the abnormalities described. Color flow and power
      Doppler ultrasonography were performed on the normal sagittal solar distal
      phalanx, on the impar distal sesamoidean ligament, and at the insertion of the
      deep digital flexor tendon on the facies flexoria of the distal phalanx. Power
      Doppler in these horses showed blood flow at 0.16-0.48 kHz at the tip of the
      distal phalanx and at 0.16 kHz at the deep digital flexor tendon insertion and in
      the impar distal sesamoidean ligament. Using color flow Doppler in normal horses
      mean blood flows ranged from 1.8 to 5.4 cm/s at the tip of the distal phalanx and
      1.8-2.0 cm/s at the deep digital flexor tendon insertion and in the impar distal
      sesamoidean ligament.

PMID- 15487571
TI  - Orchitis in two dogs with Rocky Mountain spotted fever.
AB  - Two dogs with testicular swelling were sonographically diagnosed with orchitis
      and were subsequently diagnosed with Rocky Mountain spotted fever (RMSF). Use of
      both gray scale and color Doppler sonography allowed for differentiation of
      orchitis from neoplasia and torsion. While only experimentally induced RMSF is
      reported to cause orchitis in dogs, it should be considered in any dog with
      vascular insult to the testes, especially when other signs of systemic illness
      are involved.

PMID- 15487573
TI  - Use of photon fields with noncoincident isocenters to improve homogeneity of dose
      distribution.
AB  - To compare changes in dose distribution in irregularly shaped volumes treated
      using fields with noncoincident isocenters compared with fields with coincident
      isocenters. The hypothesis was that use of fields with noncoincident isocenters
      would result in improved homogeneity of dose distribution. We chose to test the
      hypothesis in canine nasal tumors because of the increased dorsoventral thickness
      of the caudal compared with the rostral nasal cavity. Computed tomography images
      from eight dogs with nasal tumors were selected. A tissue-contouring program was
      used to outline contours, including the mandible as a normal tissue structure and
      the planning target volume (PTV), divided into a rostral and caudal volume. A
      traditional computerized treatment plan consisting of two parallel-opposed fields
      was constructed for each dog. A second treatment plan using a third caudally
      located field having a different isocenter was constructed for comparison. Dose
      volume histograms were generated and compared for each contoured structure in
      both plans. In all dogs the use of noncoincident fields resulted in increased
      dose to the ethmoid region through the caudal field. Minimum dose in the caudal
      tumor PTV increased as well. At the same time, dose delivered to the mandible,
      prone to develop significant side effects, was lower in all dogs with the use of
      noncoincident fields, as it was possible to reduce the dose delivered from the
      ventral field. Use of photon fields with noncoincident isocenters can improve the
      dose distribution in irregularly shaped volumes in comparison with fields with
      coincident isocenters. Improved tumor dose distribution was achieved with the
      addition of a smaller field having a different isocenter.

PMID- 15487572
TI  - Unexpected toxicity following use of gemcitabine as a radiosensitizer in head and
      neck carcinomas: a veterinary radiation therapy oncology group pilot study.
AB  - Gemcitabine (2',2'-difluorodeoxycytidine) was given intravenously twice weekly to
      10 cats with oral squamous cell carcinoma and 15 dogs with nasal carcinoma
      undergoing radiotherapy as a radiosensitizing agent. The average total radiation
      dose was 50 Gy for dogs and 54 Gy for cats given Monday-Friday (planned dose of
      54 and 57 Gy, respectively). Dogs received an average of five doses of
      gemcitabine beginning at 50 mg/m2, and cats received an average of five doses of
      gemcitabine beginning at 25 mg/m2. Twelve of 15 dogs and five of 10 cats required
      chemotherapy dose reduction or postponement because of hematologic or normal
      tissue toxicity. The results herein do not support the use of gemcitabine at the
      studied dose and schedule, as significant hematologic and local tissue toxicity
      was observed in the studied patients. Pharmacokinetic data are necessary to best
      define the efficacy and optimal dose and schedule of gemcitabine in combination
      with traditional radiotherapy.

PMID- 15487574
TI  - A survey of veterinary radiation facilities in the United States during 2001.
AB  - A survey of veterinary radiation therapy facilities in the United States was done
      in 2001 to determine the type of equipment available, radiation protocols used,
      case load, tumor types irradiated, as well as other details of the practice of
      radiation oncology. A total of 42 sites were identified and included 17 (40%)
      academic institutions, and 25 (60%) private practice external beam radiation
      facilities. The overall response rate was 79% (33/42 responded). Based on this
      survey there is substantial variation between facilities in all aspects ranging
      from equipment and personnel to radiation protocols and caseloads. American
      College of Veterinary Radiology boarded radiation oncologists direct 76% of the
      radiation facilities at academic institutions and 60% of the private practice
      facilities. Three facilities had orthovoltage radiation units only, and 30
      facilities had mega-voltage equipment: cobalt 60 or linear accelerator. A total
      of 18 facilities had linear accelerators with three of these off site at a human
      radiation facility. Patient load information was available from 31 sites (74% of
      the radiation facilities in the United States), and based on the responses 2790
      dogs and 1081 cats were irradiated in 2001. Canine mast cell tumors were the most
      frequently irradiated tumor. This represents the first survey of veterinary
      radiation facilities in the United States and provides information on the
      specialty of veterinary radiation oncology.

PMID- 15487575
TI  - Message from 'The CNA President ....

PMID- 15487576
TI  - Great successes for nurses and nursing practice this session!

PMID- 15487577
TI  - Colorado Nurses Association and Centennial honored by state legislators.

PMID- 15487578
TI  - The title "nurse" now protected in Colorado.

PMID- 15487579
TI  - The Colorado Nurse Practice Act: 1904-2004.

PMID- 15487580
TI  - I enjoy your newsletter.

PMID- 15487581
TI  - Health care and Earth care.

PMID- 15487582
TI  - Rising cap rates offer big upside in Medicare Advantage plans.

PMID- 15487583
TI  - Check these rates for across-the-board comparison of California groups.

PMID- 15487584
TI  - InterStudy data: HMO penetration lower, but enrollment declines have leveled off.

PMID- 15487585
TI  - Capitation a successful reimbursement mechanism for California Medi-Cal.

PMID- 15487586
TI  - The genetic structure of Oreochromis spp. (Tilapia) populations in Malaysia as
      revealed by microsatellite DNA analysis.
AB  - The genetic make-up of five populations of Oreochromis spp. was examined by
      microsatellite analysis. Eleven polymorphic microsatellite loci showed
      significant departures from the Hardy-Weinberg equilibrium. The mean
      heterozygosity ranged from 0.6280 to 0.7040 for each population. The genetic
      distance values showed a clear separation between O. niloticus and O.
      mossambicus. The differentiation of the O. niloticus populations was then tested
      with various genetic measures, which are based on both the Infinite Allele and
      the Stepwise Mutation models. All these measures grouped the populations
      similarly.

PMID- 15487587
TI  - Gene frequency distribution of the BoLA-DRB3 locus in Saavedreno Creole dairy
      cattle.
AB  - The objective of this study is to describe the gene frequency distribution of the
      bovine lymphocyte antigen (BoLA)-DRB3 locus in Saavedreno Creole dairy cattle and
      to compare it with previously reported patterns in other cattle breeds. One
      hundred and twenty-five Saavedreno Creole dairy cattle were genotyped for the
      BoLA-DRB3.2 allele by polymerase chain reaction and restriction fragment length
      polymorphism. Twenty-two out of 53 previously identified BoLA-DRB3.2 alleles were
      detected, with gene frequencies ranging from 0.4 to 16.8%. Seventy percent of the
      variation corresponded to the seven most frequent alleles (BoLA-DRB3.2*7, *8,
      *11, *16, *27, *36, and *37). The studied population exhibits a high degree of
      expected heterozygosity (he = 0.919). The FIS index did not show significant
      deviation from Hardy-Weinberg equilibrium. However, the neutrality test showed an
      even gene frequency distribution. This result could be better explained assuming
      balancing selection instead of neutral or positive selection for one or a few
      alleles. In conclusion, the results of this study demonstrated that BoLA-DRB3.2
      is a highly polymorphic locus in Saavedreno Creole dairy cattle, with significant
      variation in allele frequency among cattle breeds.

PMID- 15487588
TI  - Inheritance of lysosomal acid beta-galactosidase activity and gangliosides in
      crosses of DBA/2J and knockout mice.
AB  - GM1 gangliosidosis is a progressive neurodegenerative disease caused by
      deficiencies in lysosomal acid beta-galactosidase (beta-gal) and involves
      accumulation and storage of ganglioside GM1 and its asialo form (GA1) in brain
      and visceral tissues. Similar to the infantile/juvenile human disease forms,
      B6/129Sv beta-gal knockout (ko) mice express residual tissue beta-gal activity
      and significant elevations of brain GM1, GA1, and total gangliosides. Previous
      studies suggested that inbred DBA/2J (D2) mice may model a mild form of the human
      disease since total brain ganglioside and GM1 concentration is higher while beta
      gal specific activity is lower (by 70-80%) in D2 mice than in inbred C57BL/6J
      (B6) mice and other mouse strains. A developmental genetic analysis was conducted
      to determine if the genes encoding beta-gal (Bgl) in the D2 and the ko mice were
      functionally allelic and if the reduced brain beta-gal activity in D2 mice could
      account for elevations in total brain gangliosides and GM1. Crosses were made
      between D2 mice homozygous for the Bgld allele (d/d), and either B6/129Sv mice
      heterozygous for the Bgl+ allele (+/-) or homozygous for the ko Bgl- allele (-/-)
      to generate d/+ and d/- mice. Specific beta-gal activity (nmol/mg protein/h)
      showed additive inheritance in brain, liver, and kidney at juvenile (21 days) and
      adult (255 days) ages with the d/- mice having only about 16% of the beta-gal
      activity as that in the +/+ mice. These results indicate that the Bgl genes in
      the D2 and the ko mice are noncomplementing functional alleles. However, the d/-
      mice did not express GA1 and had total brain ganglioside and GM1 concentrations
      similar to those in the d/+ and +/+ mice. These results suggest that the reduced
      brain beta-gal activity alone cannot account for the elevation of total brain
      gangliosides and GM1 in the D2 mice.

PMID- 15487589
TI  - Molecular genetic variation in Chinese populations of three subspecies of
      Hippophae rhamnoides.
AB  - To provide a population-level genetic profile for investigation and conservation
      of genetic diversity of the sea buckthorn (Hippophae rhamnoides L.), 300
      individuals of fifteen natural populations of sea buckthorn in China were
      analyzed by using ISSR (inter-simple sequence repeats) markers. On the basis of
      Shannon's index and Nei's genetic diversity, the mean genetic diversity detected
      in the natural populations of Hippophae rhamnoides ssp. yunnanensis, ssp.
      sinensis, and ssp. gyantsensis was 0.1944, 0.2169, and 0.1372, respectively. The
      coefficient of gene differentiation (Gst) of seven ssp. yunnanensis populations
      is 0.2790, and that of seven ssp. sinensis populations is 0.4184. This means that
      28% of the total molecular variance of seven ssp. yunnanensis populations existed
      among populations, and 42% for seven ssp. sinensis populations, suggesting that
      the subspecies have different genetic structures. No significant correlation
      between genetic and geographic distances of the populations was found using ISSR
      markers.

PMID- 15487590
TI  - Assessing genetic diversity of Ginkgo biloba l. (Ginkgoaceae) populations from
      China by RAPD markers.
AB  - Genetic diversity and differentiation of nine populations of Ginkgo biloba L.
      (Ginkgoaceae)from China were evaluated using RAPD. Of 47 clear and repeatable
      RAPD bands, 46 were polymorphic (overall polymorphism = 97.9%). A ranged from
      1.57 to 1.83 with a mean of 1.75. Mean He was 0.3159 (0.2429-0.3603). The Shannon
      index ranged from 0.3432 to 0.5119 with a mean of 0.4489. The GST was 0.1609 and
      AMOVA analysis indicated 89% of the variation within populations. UPGMA clustered
      the 9 populations into two groups: one containing only population JF and the
      other including 8 populations. Genetic diversity and differentiation of Chinese
      populations were higher than those of Korean and North American populations,
      which are ultimately descended from China, as reported previously.

PMID- 15487591
TI  - Isolation and characterization of a Jerky and JRK/JH8 like gene, tigger
      transposable element derived 7, TIGD7.

PMID- 15487592
TI  - Lassa virus.
AB  - Lassa virus is a RNA virus belonging to the family of Arenaviridae. It was
      discovered as the causative agent of a hemorrhagic fever--Lassa fever--about 30
      years ago. Lassa fever is endemic in West Africa and is estimated to affect some
      100,000 people annually. Great progress in the understanding of the life cycle of
      arenaviruses, including Lassa virus, has been made in recent years. New insights
      have been gained in the pathogenesis and molecular epidemiology of Lassa fever,
      and state-of the-art technologies for diagnosing this life-threatening disease
      have been developed. The intention of this review is to summarize in particular
      the recent literature on Lassa virus and Lassa fever. Several aspects ranging
      from basic research up to clinical practice and laboratory diagnosis are
      discussed and linked together.

PMID- 15487593
TI  - Yellow fever: the recurring plague.
AB  - Despite the availability of a safe and efficacious vaccine, yellow fever (YF)
      remains a disease of significant public health importance, with an estimated
      200,000 cases and 30,000 deaths annually. The disease is endemic in tropical
      regions of Africa and South America; nearly 90% of YF cases and deaths occur in
      Africa. It is a significant hazard to unvaccinated travelers to these endemic
      areas. Virus transmission occurs between humans, mosquitoes, and monkeys. The
      mosquito, the true reservoir of YF, is infected throughout its life, and can
      transmit the virus transovarially through infected eggs. Man and monkeys, on the
      other hand, play the role of temporary amplifiers of the virus available for
      mosquito infection. Recent increases in the density and distribution of the urban
      mosquito vector, Aedes aegypti, as well as the rise in air travel increase the
      risk of introduction and spread of yellow fever to North and Central America, the
      Caribbean, the Middle East, Asia, Australia, and Oceania. It is an acute
      infectious disease characterized by sudden onset with a two-phase development,
      separated by a short period of remission. The clinical spectrum of yellow fever
      varies from very mild, nonspecific, febrile illness to a fulminating, sometimes
      fatal disease with pathognomic features. In severe cases, jaundice, bleeding
      diathesis, with hepatorenal involvement are common. The case fatality rate of
      severe yellow fever is 50% or higher. The pathogenesis and pathophysiology of the
      disease are poorly understood and have not been the subject of modern clinical
      research. There is no specific treatment for YF, making the management of YF
      patients extremely problematic. YF is a zoonotic disease that cannot be
      eradicated, therefore instituting preventive vaccination through routine
      childhood vaccination in endemic countries, can significantly reduce the burden
      of the disease. The distinctive properties of lifelong immunity after a single
      dose of yellow fever vaccination are the basis of the new applications of yellow
      fever 17D virus as a vector for foreign genes, "the chimeric vaccine,' and the
      promise of developing new vaccines against other viruses, and possibly against
      cancers.

PMID- 15487594
TI  - The course of maternal depressive symptoms and maternal sensitivity as predictors
      of attachment security at 36 months.
AB  - We examined the course of maternal depressive symptoms and children's attachment
      security at 36 months in a large sample of mother-child pairs from 10 sites
      across the country participating in the NICHD Study of Early Child Care (N =
      1077). Maternal depressive symptoms predicted higher rates of insecure
      attachment. Women who reported intermittent symptoms across the first 36 months
      had preschoolers who were more likely to be classified as insecure C or D; women
      with chronic symptoms were more likely to have preschoolers who were classified
      as insecure D. Symptoms reported only during the first 15 months were not
      associated with elevated rates of later insecurity. After controlling for
      potentially confounding demographic variables, maternal sensitivity (observed at
      6, 15, 24, and 36 months) did not meaningfully account for links between
      attachment security and patterns of depressive symptoms. However, the course and
      timing of maternal depressive symptoms interacted with maternal sensitivity to
      predict insecurity. Women with late, intermittent, or chronic symptoms who were
      also low in sensitivity were more likely to have preschoolers who were insecure,
      in contrast to symptomatic women who were high in sensitivity. These data have
      implications for understanding the combined impact of maternal depressive
      symptoms and maternal sensitivity on children's socioemotional development.

PMID- 15487595
TI  - Forming attachments in foster care: infant attachment behaviors during the first
      2 months of placement.
AB  - This study investigated the development of attachment relationships in 38 foster
      infant-caregiver dyads over the first 2 months of placement. We used the Parent
      Attachment Diary to measure foster infants' daily attachment behaviors, the Adult
      Attachment Interview to examine foster parents' attachment states of mind, and
      Ainsworth's Strange Situation to capture attachment classifications. We examined
      differences in diary scales (secure, avoidant, resistant, and coherence) as they
      related to age at placement and foster parent attachment, using hierarchical
      linear modeling and analyses of variance. The results indicated infants with
      autonomous foster parents and infants placed at younger ages showed higher early
      and overall levels of secure behavior, less avoidant behavior, and more coherent
      attachment strategies compared to infants placed with nonautonomous foster
      parents. Changes in attachment behaviors over time were not predicted by the
      models; however, there was a significant decrease in the daily coherence of
      attachment behaviors associated with Strange Situation disorganization. Finally,
      we found significant concordance between the diary and Strange Situation scales
      for secure and avoidant behaviors.

PMID- 15487596
TI  - Infant joint attention skill and preschool behavioral outcomes in at-risk
      children.
AB  - This study examined whether infant joint attention (JA) skills predicted social
      behaviors in a sample of at-risk preschool children (n = 30) with a history of
      prenatal exposure to cocaine. JA behaviors were assessed with the Early Social
      and Communication Scales at 12, 15, and 18 months of age. Three classes of JA
      were measured: Initiating JA (IJA), Responding to JA (RJA), and Requests.
      Behavioral outcomes were measured at 36 months and included ratings of disruptive
      and withdrawn behaviors and social competence. JA behaviors were related to
      behavioral outcomes after controlling for language and cognitive ability. The
      functionally distinct uses of JA were differentially related to behavioral
      outcome. IJA negatively predicted disruptive behaviors, whereas Requests
      positively predicted disruptive behaviors. Infant RJA negatively predicted
      withdrawn behaviors and positively predicted social competence. These results are
      interpreted in the context of competing theories that attempt to explain
      variability in the expression of JA skills in the second year of life.

PMID- 15487597
TI  - Attachment in infancy and preschool in low socioeconomic status rural Appalachian
      children: stability and change and relations to preschool and kindergarten
      competence.
AB  - Attachment classifications were obtained from the Strange Situation at 15 months
      and at 4 years for a sample of 82 low socioeconomic status rural Appalachian
      children. The rate of secure attachment in infancy was 50.5%, and the majority of
      insecure infants were disorganized. At 4 years of age 61.2% of children were
      secure; early secure relationships were likely to be maintained, and about half
      of the insecure infants changed to a secure classification by 4 years. Overall,
      there was low but significant stability in attachment at the level of
      secure/insecure. Comparisons of (a) children who changed from insecure to secure
      with those who were stable insecure and (b) stable secure children with those who
      changed from secure to insecure identified contextual, child, and maternal
      interaction factors associated with attaining secure attachment. Assessments of
      cognitive and socioemotional competence at 4 years and kindergarten age suggested
      a protective effect of secure infant attachment but little benefit from secure
      preschool attachment.

PMID- 15487598
TI  - Codevelopment of externalizing and internalizing problems in early childhood.
AB  - Using cross-domain latent growth modeling, we examined trajectories of
      externalizing and internalizing problems in disadvantaged boys followed from ages
      2 to 6 years (N = 303). On average, externalizing problems gradually decreased
      and internalizing problems gradually increased. However, we found significant
      variability in individual-level trajectories. Higher levels of externalizing
      problems were associated with higher levels of internalizing problems; rates of
      change were also positively correlated across domains. In addition, high levels
      of externalizing problems predicted rapid increases in internalizing problems. In
      follow-up analyses involving child and parenting factors, the combination of high
      negative emotionality, low fearfulness, and high negative maternal control
      preceded high, nondecreasing externalizing trajectories. The combination of high
      negative emotionality, high fearfulness, and high negative maternal control
      preceded high, increasing internalizing trajectories. Taken together, the results
      indicate both general and specific processes in the development of early
      externalizing and internalizing problems.

PMID- 15487599
TI  - The expression and regulation of negative emotions: risk factors for young
      children's peer victimization.
AB  - Using a short-term longitudinal design, internalizing and externalizing emotions
      were examined as risk factors for being victimized by peers in early childhood.
      Regulation, aggression, and withdrawal were also tested as mediators. We found
      that anger, mediated by aggression and regulation, positively predicted being
      victimized, although the way in which anger related to victimization risk varied
      for boys and girls and across time. These findings were robust, particularly for
      girls, attesting to the importance of externalizing variables as risk factors for
      young children's victimization. Support for internalizing variables as risk
      factors for being victimized was weak. The implications of the findings for
      developmental models connecting symptomatology and victimization are discussed.

PMID- 15487600
TI  - Emotion understanding in postinstitutionalized Eastern European children.
AB  - To examine the effects of early emotional neglect on children's affective
      development, we assessed children who had experienced institutionalized care
      prior to adoption into family environments. One task required children to
      identify photographs of facial expressions of emotion. A second task required
      children to match facial expressions to an emotional situation. Internationally
      adopted, postinstitutionalized children had difficulty identifying facial
      expressions of emotion. In addition, postinstitutionalized children had
      significant difficulty matching appropriate facial expressions to happy, sad, and
      fearful scenarios. However, postinstitutionalized children performed as well as
      comparison children when asked to identify and match angry facial expressions.
      These results are discussed in terms of the importance of emotional input early
      in life on later developmental organization.

PMID- 15487601
TI  - Children's emotion processing: relations to emotionality and aggression.
AB  - We examined the relations between emotionality, emotion processing, and
      aggression in 182 first- and second-grade children. Consistent with Tomkins' and
      Izard's theoretical predictions, emotionality correlated with emotion processing.
      In particular, the happiness component of emotionality correlated with emotion
      attribution accuracy and empathy, the anger component correlated with anger
      attribution bias and empathy, and the fear component correlated with fear
      attribution bias. Multiple emotion processing deficits--including emotion
      attribution accuracy, anger attribution bias, and self-report of empathy--placed
      children at risk for heightened levels of teacher-reported aggression.
      Mediational analyses revealed that an emotion processing risk index fit a model
      of significant partial mediation between happiness and aggression but not between
      anger and aggression. The results suggest the multifaceted manner in which
      children's emotion experiences may influence the development of aggressive
      tendencies.

PMID- 15487602
TI  - Stress responsivity in children with externalizing behavior disorders.
AB  - Patterns of lower autonomic nervous system (ANS) and hypothalamic-pituitary
      adrenal (HPA) axis activity have been found in children with oppositional defiant
      disorder (ODD). The aim of the present study was to investigate whether children
      with attention-deficit/hyperactivity disorder (ADHD) differ from ODD children
      with (OD/AD) or without comorbid ADHD in ANS and HPA axis activity under baseline
      and stressful conditions. The effects of stress on cortisol, heart rate (HR), and
      skin conductance level (SCL) were studied in 95 children (26 normal control [NC]
      children and 69 child psychiatric patients referred for externalizing behavior
      problems [15 ODD, 31 OD/AD, and 23 ADHD]). No baseline differences were found in
      cortisol between the four groups. However, the ODD and OD/AD groups showed a
      significantly weaker cortisol response to stress compared to the ADHD and NC
      groups; the ADHD group had a similar cortisol response as the NC group. Within
      the ODD group this pattern of low cortisol responsivity was most clearly present
      in the more severely affected inpatients. With respect to HR, the ODD group had a
      significantly lower HR during baseline and stressful conditions. The higher HR
      levels in the OD/AD and ADHD groups were likely to be caused by methylphenidate.
      The externalizing groups had significantly lower SCL levels, and no differences
      were found between these groups. It was concluded that differences in cortisol
      responsivity during stress exposure are important in distinguishing within a
      group of children with externalizing behavior between those with ODD and ADHD.

PMID- 15487603
TI  - Testing the prenatal hormone hypothesis of tic-related disorders: gender identity
      and gender role behavior.
AB  - The hypothesis that prenatal masculinization of the brain increases risk of tic
      disorders in postnatal life was tested by measuring gender and gender role
      behavior in 89 children and adults with a clinical diagnosis of Tourette syndrome
      or obsessive compulsive disorder and 67 healthy, unaffected children and adults.
      Consistent with this hypothesis, a tic disorder in females was associated with
      more gender dysphoria, increased masculine play preferences, and a more typically
      "masculine" pattern of performance on two sex-typed spatial tasks. Males with tic
      disorders reported increased masculine play preferences, and the strength of
      these preferences was positively associated with the severity of tic symptoms. In
      addition, unlike their female counterparts, males with tic disorders showed a
      relative impairment in mental rotation ability. These behavioral profiles are
      consistent with those of children who have verifiable elevations in prenatal
      androgen levels. These findings therefore support the hypothesis that an altered
      androgen-dependent process of sexual differentiation during prenatal life may
      contribute to the development of tic-related disorders.

PMID- 15487604
TI  - Temperament profiles associated with internalizing and externalizing problems in
      preadolescence.
AB  - This study investigates how temperament factors are linked to internalizing and
      externalizing problems in a Dutch population sample of preadolescents (N = 2230).
      Internalizing and externalizing problems were assessed by the Child Behavior
      Checklist and the Youth Self-Report and temperament was evaluated by the parent
      version of the Revised Early Adolescent Temperament Questionnaire. Temperament
      profiles were examined in children with (a) neither internalizing nor
      externalizing problems, (b) only internalizing problems, (c) only externalizing
      problems, and (d) both internalizing and externalizing problems. The results
      suggest clearly diverging temperament profiles for these groups of children, with
      High-Intensity Pleasure and Shyness (representing the broad dimension of
      Surgency) steering the conditional probability of internalizing and externalizing
      problems (direction markers), Frustration mainly being related to maladaptation
      in general (severity marker), and Fear and Effortful Control being associated
      with both the severity and the direction of internalizing and externalizing
      problems, respectively. Girls and boys differed in the distribution across the
      problem groups, but the associations between temperament and psychopathology were
      comparable for both genders.

PMID- 15487605
TI  - From boys to men: predicting adult adaptation from middle childhood sociometric
      status.
AB  - This report examines the predictive validity of sociometric status at age 9-10 to
      young adult (age 23-24) antisocial behavior, work and school engagement, and
      arrests using Oregon Youth Study males (N = 206). A variety of analytic
      strategies included (a) multivariate analyses to examine the variation in adult
      adaptation as a function of sociometric classification at age 9-10, (b)
      regression analyses to evaluate the relative contribution of "liked most" and
      "liked least" peer nominations, and (c) structural equation modeling to predict
      the young adult outcome constructs from social preference at age 9-10. Contrary
      to expectation, when controlling for early antisocial behavior and academic
      skills, boys' social preference scores still predicted young adult outcomes.
      Longitudinal findings are discussed with respect to the salience of male peer
      rejection in middle childhood and the social developmental processes that may
      account for the predictive validity of peer rejection.

PMID- 15487606
TI  - A prospective study of the association among impaired executive functioning,
      childhood attentional problems, and the development of bipolar disorder.
AB  - Studies of adults who have been diagnosed with, and treated for, bipolar disorder
      have shown that these patients exhibit impairment on measures of executive
      functioning. However, it is unclear whether executive dysfunction precedes the
      diagnosis of bipolar illness, or develops subsequent to its onset. Moreover,
      investigators have failed to control for the effects of premorbid attentional
      problems on cognitive performance in these patients. The present authors explored
      these questions using data from a longitudinal prospective study of individuals
      at risk for major mood disorder. Results revealed that 67% of participants who
      met criteria for bipolar disorder in young adulthood showed impairment on the
      Wisconsin Card Sorting Test (WCST) when they were assessed during adolescence, as
      compared with 17% of individuals with no major mood diagnosis, and 19% with
      unipolar depression. This association between performance on the WCST and bipolar
      illness was not accounted for by high rates of premorbid attentional disturbance.
      In fact, among participants with early attentional problems, only those who
      ultimately developed bipolar disorder exhibited impairment on the WCST. Early
      attentional problems that preceded unipolar depression or no mood disorder were
      not associated with executive dysfunction.

PMID- 15487607
TI  - Breaking the silence on prevention of unsafe abortion in Africa.

PMID- 15487608
TI  - Saving African women's lives from unsafe abortion--everyone has a role to play.

PMID- 15487609
TI  - International commitments and guidance on unsafe abortion.
AB  - Most of Africa's 54 countries have restrictive abortion laws, outdated remnants
      of former colonial laws that result in nearly five million unsafe abortions
      annually. To stem maternal mortality and morbidity, it is essential to look
      beyond strictly medical or health system approaches to solving this critical
      public health problem. The issue must be approached from a human rights
      perspective that emphasises the individual's right to self-determination. This
      article examines ways in which advocates can use established human rights
      standards, international consensus documents, and the World Health Organization's
      new technical and policy guidance for health systems to press for safer abortion
      care for African women.

PMID- 15487610
TI  - Breaking the cycle of unsafe abortion in Africa.
AB  - Globally, nearly half of all maternal deaths from unsafe abortion occur in
      Africa. Abortion-related deaths and injuries are especially tragic, because when
      properly performed, abortion is one of the safest of all medical procedures.
      Factors contributing to this neglected public health crisis include inadequate
      health care resources and infrastructure, restrictive laws and policies, stigma,
      and women's lack of empowerment. Actions needed include making high quality
      abortion care more available and accessible, especially at the primary care level
      and to the full extent permitted by law. Others include removing medically
      unnecessary policy and legal restrictions on abortion; and better informing
      health care professionals, women and communities about the impact of unsafe
      abortion and the circumstances under which abortion can be legally obtained.

PMID- 15487611
TI  - Woman-centred safe abortion care in Africa.
AB  - Unsafe abortion in Africa affects not only women, but also their children,
      families and communities To counter this extremely costly yet easily preventable
      problem, African nations must ensure that health systems are trained and equipped
      to help prevent unwanted pregnancy, to treat women in emergency situations, and
      to make safe abortion services available to the full extent of the law. One
      critical component of this process is comprehensive woman-centred care, an
      approach that emphasises access, choice and quality of services. This article
      examines this and the obstacles to safe abortion care, as well as how they can be
      overcome through broad-based partnerships.

PMID- 15487612
TI  - The power dynamics perpetuating unsafe abortion in Africa: a feminist
      perspective.
AB  - Tens of thousands of African women die every year because societies and
      governments either ignore the issue of unsafe abortion or actively refuse to
      address it. This paper explores the issue of abortion from a feminist
      perspective, centrally arguing that finding appropriate strategies to reclaim
      women's power at an individual and social level is a central lever for developing
      effective strategies to increase women's access to safe abortion services. The
      paper emphasises the central role of patriarchy in shaping the ways power plays
      itself out in individual relationships, and at social, economic and political
      levels. The ideology of male superiority denies abortion as an important issue of
      status and frames the morality, legality and socio-cultural attitudes towards
      abortion. Patriarchy sculpts unequal gender power relationships and takes power
      away from women in making decisions about their bodies. Other forms of power such
      as economic inequality, discourse and power within relationships are also
      explored. Recommended solutions to shifting the power dynamics around the issue
      include a combination of public health, rights-based, legal reform and social
      justice approaches.

PMID- 15487613
TI  - Planning for sustainable access to technology: an essential element of safe
      abortion care.

PMID- 15487614
TI  - Reducing maternal mortality from unsafe abortion among adolescents in Africa.
AB  - Initiation of sexual behaviour is a normal part of human development and it often
      occurs during adolescence. This is common and universal to all societies and
      cultures around the world with profound implications for sexual and reproductive
      health. Adolescence is the period when much of the changes that are associated
      with becoming an adult take place. These are changes which societies expect and
      welcome. Unsafe abortion is a major cause of maternal mortality among adolescents
      in Africa. The need for a public health response to unsafe abortion in Africa is
      compelling. It is important to focus on primary prevention including the
      provision of appropriate sexuality education and information as well as
      supportive services to allow adolescents to prevent unwanted pregnancy. Secondary
      prevention efforts include prompt diagnosis and treatment of complications by
      ensuring that services are made more responsive to the needs of adolescents, and
      by improving access to and quality of care for them. Post-abortion care in
      adolescents must include contraception as well as several elements of life
      planning.

PMID- 15487615
TI  - Medical abortion: the Tunisian experience.
AB  - This paper reports the Tunisian experience of medical abortion. The project
      started in 1998 with a small introductory study at the obstetric and gynaecology
      department of a university hospital and was later extended step by step to other
      family planning and public health centres that provided abortion services. The
      study was first conducted on 264 women using the modified regimen of 200mg
      mifepristone, followed 48 hours later by 400 microg misoprostol in women seeking
      pregnancy of maximum 56 days of amenorrhoea. This gave a success rate of 91.1%.
      Results from further studies in other locations showed increasing success rates
      of 94.4% and 95.6%, with high acceptability and satisfaction among users and
      providers The registration and effective introduction of medical abortion was
      quite rapid. Following successful conduct of the pilot study, intervention
      programmes were designed and implemented to improve the capacity of providers in
      providing safe medical abortion.

PMID- 15487616
TI  - Destigmatising abortion: expanding community awareness of abortion as a
      reproductive health issue in Ghana.
AB  - Traditional and cultural values, social perceptions, religious teachings and
      criminalisation have facilitated stigmatisation of abortion in Ghana. Abortion is
      illegal in Ghana except in three instances. Though the law allows for performance
      of abortion in three circumstances, the Ghana reproductive health service policy
      did not have any induced legal abortion services component to cover the three
      exceptions until it was revised in 2003. The policy only had 'unsafe and post
      abortion' care components, and abortions performed in health facilities operated
      by the Ghana Health Service were performed under this component. Though the
      policy has been revised, women and girls who need abortion services in Ghana more
      often resort to the backstreet dangerous methods and procedures. Criminalisation
      of abortion and those who perform abortions has contributed to unsafe abortion,
      the second leading cause of maternal deaths in Ghana. Most of these are performed
      outside the formal health service structures. Traditionally, abortion is
      perceived as a shameful act and the community may shun and give a woman who has
      caused anabortion derogatory names. Would provision of legal abortion services be
      culturally acceptable within a Ghanaian community? Yes, if they are made aware of
      the reproductive health benefits of providing safe abortion services. Three major
      strategies that would help to destigmatise abortion in the community are (1) the
      liberal interpretation of the three exceptions to the law on abortion; (2)
      expanding community awareness of its reproductive health benefits; and (3)
      improving and increasing access to legal abortion services within the formal
      health facilities.

PMID- 15487617
TI  - Provision of abortion services by midwives in Limpopo province of South Africa.
AB  - South Africa's Choice on Termination of Pregnancy (CTOP) Act of 1996 allows
      provision of abortion on request up to 12 weeks of gestation and permits midwives
      who have completed required training to conduct termination of pregnancies. This
      unique codification of midwives' role in abortion care reflects legislators'
      recognition that the right to safe legal abortion would be meaningless to the
      vast majority of South African women who live in remote rural areas unless
      appropriate steps were taken to ensure their access to such services and an
      understanding that, by dint of their numbers and skills, this cadre of health
      care providers have much to offer. Though not without considerable challenges,
      experience from Limpopo Province demonstrates the important impact of involving
      midlevel providers has had in expanding the availability and accessibility of
      safe legal abortion.

PMID- 15487618
TI  - Advocacy for legal reform for safe abortion.
AB  - In Ethiopia, violation of women's reproductive rights is both a cause and a
      manifestation of women's disempowerment. Obstacles to full realisation of
      Ethiopian women's reproductive health and rights include the persistence of
      harmful traditional practices such as female genital mutilation, early marriage
      and abduction, as well as the disturbing prevalence of rape and HIV/AIDS. Unsafe
      abortion represents a particularly serious threat to women's health and lives.
      Ethiopia's status as a signatory to the Convention to Eliminate all Forms of
      Discrimination Against Women (CEDAW) and its constitutional guarantee of women's
      equality demand more aggressive action to eradicate such practices and
      inequities. After years of lobbying by women's organisations, parliamentarians
      are now reviewing a draft of the 1957 penal code, which includes numerous
      provisions addressing some of these practices and other conditions that underlie
      women's poor social and health status.

PMID- 15487619
TI  - Promoting sexual and reproductive health and rights in Nigeria through change in
      medical school curriculum.
AB  - Significant developments have occurred in the field of sexual and reproductive
      health and rights (SRHR) globally in the last decade. However, this is yet to
      translate into improved status of SRHR in developing countries. One of the
      strategies recognised worldwide for addressing the poor status of SRHR is human
      capacity building at all levels. A pilot work conducted in two federal university
      medical schools identified a major gap in knowledge among medical students on
      issues related to SRHR. This called for a review of the curriculum to enable the
      incorporation of relevant and topical issues. This article describes the
      processes leading to the adoption of the Nigerian medical schools' sexual and
      reproductive health and rights curriculum. The exercise culminated in the
      identification of internal and external stakeholders and needs of the Nigerian
      medical schools in teaching reproductive health. The participation of lecturers
      (bottom-up approach) brought about a sense of ownership of the document and
      promoted the broad consultation and participation of all participants. It also
      identified capacity building and the need for evaluation as a basis for further
      review.

PMID- 15487620
TI  - Living with HIV: challenges in reproductive health care in South Africa.
AB  - Women in Africa are facing discrimination and challenges in relation to HIV/AIDS,
      particularly regarding their sexual and reproductive health care. This includes a
      lack of information regarding HIV and pregnancy, difficulties with contraceptive
      use, negative attitudes towards childbearing, and problems in accessing safe
      legal abortions. This paper addresses these issues in South Africa, based on an
      interview study with eight key informants and a literature review. The South
      African experience should inform policy-making and programmes in relation to HIV
      and reproductive health care in other African countries.

PMID- 15487621
TI  - Communique from the "Action to Reduce Maternal Mortality in Africa" regional
      consultation on unsafe abortion. March 5-7, 2003, Addis Ababa, Ethiopia.

PMID- 15487622
TI  - Open access: publishing future or finale?

PMID- 15487623
TI  - Epithelial migration.

PMID- 15487624
TI  - Rhinolithiasis.

PMID- 15487625
TI  - Hemorrhagic polyp following intubation.

PMID- 15487626
TI  - Ossifying fibroma of the maxilla.

PMID- 15487627
TI  - Skin keloid.

PMID- 15487628
TI  - Possible central vestibular findings in a patient with a peripheral vestibular
      disorder.

PMID- 15487629
TI  - Monitoring appeal success.

PMID- 15487630
TI  - Stretching the limits of full-thickness skin grafts.

PMID- 15487631
TI  - Blindness: a sequela of sinonasal small cell neuroendocrine carcinoma.

PMID- 15487632
TI  - Unusual anomaly of the external ear.

PMID- 15487633
TI  - Hearing loss as the initial presentation of Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease is a rare type of spongiform encephalopathy. Affected
      patients present with constitutional symptoms, which progress to severe mental
      deterioration and movement disorders. Dizziness is the most common early otologic
      symptom. Few reports in the literature describe patients with Creutzfeldt-Jakob
      disease who present with sudden-onset hearing loss as their primary symptom for
      seeking treatment. This paper discusses one such patient and reviews the clinical
      presentation, treatment options, and relevant literature.

PMID- 15487634
TI  - Intracranial neuromuscularchoristoma: a case report and literature review.
AB  - Neuromuscular choristoma (NMC) is an uncommon tumor that usually involves a large
      nerve trunk. Only 28 cases of NMC have been previously reported in the English
      language literature, 17 of which involved cranial nerves. We report a new case of
      intracranial NMC that arose from a facial nerve at the cerebellopontine angle in
      a 44-year-old man. The patient was taken to surgery, where the lesion was found
      to involve the right facial nerve. The tumor was partially removed, and at the 2
      year follow-up, the patient showed no sign of recurrence.

PMID- 15487635
TI  - Grisel's syndrome: the two-hit hypothesis--a case report and literature review.
AB  - Grisel's syndrome is a rare but well-documented clinical entity. It is a
      nontraumatic, fixed rotary subluxation of C1 on C2 (atlantoaxial). Although first
      described in 1830, the exact mechanism of Grisel's syndrome remains unclear. We
      present a postoperative case of Grisel's syndrome and an extensive literature
      review, and we propose a mechanism for its pathogenesis. In addition, we propose
      a treatment algorithm for Grisel's syndrome.

PMID- 15487636
TI  - Rhinoorbital mucormycosis secondary to Rhizopus oryzae: a case report and
      literature review.
AB  - Mucormycosis is a form of fulminant invasive fungal infection of the sinonasal
      tract that often extends to the orbit, brain, palate, and skin. It is caused by
      members of the order Mucorales, and it is considered to be the most fatal fungal
      infection known to man because it is rapidly disseminated by the blood vessels.
      It is most commonly associated with diabetic ketoacidosis, hematologic
      malignancies, acquired immunodeficiency syndrome, and immunosuppressive therapy.
      This rare opportunistic infection exists in many forms, the most common of which
      is rhinocerebral mucormycosis. Treatment includes aggressive surgical debridement
      of the necrotic tissue combined with systemic antifungal therapy. In this case
      report, we describe the successful management of rhinoorbital mucormycosis, a
      subtype of the rhinocerebral variety, secondary to Rhizopus oryzae that developed
      in a patient with lymphoma. We review the diagnostic work-up and discuss the
      literature with respect to the presentation, pathophysiology, management, and
      outcome of the disease.

PMID- 15487637
TI  - Foreign body impaction: fifty years inside the nose.
AB  - An incidental finding of a foreign body in the nose is an infrequent event. When
      foreign bodies are discovered incidentally, they are usually detected during an
      investigation of chronic symptoms. We describe a case that is of interest because
      a nasal foreign body had remained clinically silent for more than 50 years.

PMID- 15487638
TI  - Laryngeal rhinosporidiosis: report of a rare case.
AB  - Extranasal manifestations of rhinosporidiosis are relatively uncommon. Laryngeal
      involvement is extremely rare, as only 3 cases have been previously reported. We
      describe a new case, which occurred in a patient with coexisting nasal
      rhinosporidiosis who presented with inspiratory stridor. Both lesions were
      completely excised under general anesthesia without the need for preliminary
      tracheostomy.

PMID- 15487639
TI  - Radiofrequency volume tissue reduction of the tonsils: case report and
      histopathologic findings.
AB  - Innovative new techniques to resect tonsillar tissue have been described in the
      recent literature. We report the case of a patient who underwent volume reduction
      of tonsillar tissue by radiofrequency energy under local anesthesia in an office
      setting. Treatment resulted in a reduction of tonsillar size with minimal pain,
      which can be attributed to the avoidance of mucosal interruption. The patient
      subsequently underwent standard tonsillectomy, which allowed us to examine the
      histopathology of the tissue that was treated with radiofrequency. In doing so,
      we noted an absence of fibrosis and preservation of normal histologic
      architecture. We conclude that performing volume reduction of tonsillar tissue by
      applying radiofrequency energy to the stroma of the tonsils without temperature
      control results in objective improvement in airway size with minimal effects on
      the histopathology of the tonsillar stroma. Mucosa-sparing tonsillar reduction
      may be a preferable alternative to other techniques of tonsillar reduction,
      especially for young children, who would experience a nearly pain-free procedure.

PMID- 15487640
TI  - Craniocervical necrotizing fasciitis of odontogenic origin with mediastinal
      extension.
AB  - We review an interesting case of craniocervical necrotizing fasciitis with
      thoracic extension in an immunocompetent 44-year-old man. The patient underwent
      aggressive medical and surgical management during a long hospitalization.
      Multiple surgical debridements, including transcervical mediastinal debridement,
      and eventually a thoracotomy for mediastinal abscess were required. The patient
      eventually recovered, and 3 months later he showed no sign of complications or
      recurrence. Craniocervical necrotizing fasciitis is a fulminant soft-tissue
      infection, usually of odontogenic origin, that requires prompt identification and
      treatment to ensure survival. Broad-spectrum intravenous antibiotics, aggressive
      surgical debridement and wound care, hyperbaric oxygen, and good intensive care
      are the mainstays of treatment.

PMID- 15487641
TI  - The pathogenesis of reproductive failure induced in sheep by the ingestion of
      Ateleia glazioviana.
AB  - Seventeen pregnant ewes were orally fed variable amounts of either green or dried
      leaves of Ateleia glazioviana in 1 through 24 daily doses. All 17 ewes manifested
      some form of reproductive failure. Nine (52.9%) aborted their fetuses at 4
      through 36 d after starting being fed the leaves of the plant; 1 had a stillbirth
      and in another 1 intrauterine fetal death was diagnosed. The other 6 ewes
      delivered 8 weak lambs, 7 of which died from few min to 48 h after birth. Three
      ewes had neurologic disturbances and loss of weight. Thirteen ewes were
      euthanatized 1-48 h after lambing or pregnancy loss; 2 of them had gross and
      histopathological changes related to the A glazioviana. Gross and
      histopathological changes observed in 7 lambs and in a stillborn, and
      histopathological changes found in 4 aborted fetuses from A glazioviana-fed ewes,
      were similar to those found in spontaneous poisoning by A glazioviana in adult
      cattle. It is concluded that A glazioviana has a powerful abortifacient activity
      whether ingested green or dried. The abortions caused by A glazioviana were not
      due to placental damage, but rather to transplacental induced fetal lesions
      consisting of toxic cardiomyopathy and spongy degeneration of the white matter of
      the brain. Fetuses succumbing to these lesions were expelled from the uterus;
      those not lethally affected are born weak with meager chances to survive.

PMID- 15487642
TI  - Effects on growth and cadmium residues from feeding cadmium-added diets with and
      without montmorillonite nanocomposite to growing pigs.
AB  - One hundred and ninety-two crossbred pigs (barrows, Duroc x Landrace x Yorkshine,
      initial weight 27.6 kg) were used to evaluate the effects of montmorillonite
      nanocomposite (MNC) on cadmium (Cd) retention in tissues of growing pigs. The
      animals were randomly assigned to 2 supplementations of Cd (0 or 10 mg/kg) and 2
      levels of MNC (0 or 0.5%) in a 2x2 factorial arrangement. Each group was fed corn
      soybean basal diets and consisted of 3 replications of 16 pigs. The feeding
      experiment lasted 83 d. Pig growth performances decreased significantly by
      addition of 10 mg Cd/kg (p<0.05) and improved with supplementation of MNC
      (p<0.05). Addition of MNC with Cd decreased Cd retentions in muscle, liver,
      kidney, spleen, thymus and lymphaden of pigs (p<0.05). MNC also decreased tissue
      Cd residues of pigs fed the diet without added Cd (p>0.05). There were decreased
      iron levels and increased copper levels in serum and liver of 10 mg Cd/kg
      treatment (p<0.05). Zinc content in serum and liver was not affected by the
      addition of Cd (p>0.05). Serum and liver iron, copper and zinc concentrations of
      pigs fed MNC without added Cd were unaffected by MNC (p>0.05).

PMID- 15487643
TI  - Interaction between enrofloxacin and monensin in broiler chickens.
AB  - Enrofloxacin, a fluoroquinolone, and its interaction with monensin, an ionophore
      drug, was studied to explore the influence of enrofloxacin on drug metabolizing
      enzymes that can lead to physiological and toxicological consequences upon
      coadministration with monensin in broiler chickens. Group I, treated with 100 mg
      monesin/kg feed from 1 d old to 41st d of age, did not show any influence on
      aniline hydroxylase and cytochrome b5 levels. Group II, treated with 10 mg
      enrofloxacin/kg body weight per os for three consecutive days on 33rd, 34th, 35th
      d of age, had a highly significant decrease in aniline hydroxylase on 38th d (ie
      on 3rd d post-treatment with enrofloxacin); a reversal effect was noticed on the
      41st day (ie on 6th d post-treatment with enrofloxacin). There was no alteration
      in cytochrome b5 level. Group III with monensin and enrofloxacin coadministration
      100 mg monensin/kg feed from 1 d old to the 41st day + 10 mg enrofloxacin/kg body
      weight, per os for 3 consecutive days on the 33rd, 34th, 35th d of age) had a
      significant decrease in aniline hydroxylase level on the 3rd d post-treatment
      with enrofloxacin, but an elevation tending to reach normal on the 6th d post
      treatment with enrofloxacin. Monensin + enrofloxacin coadministration did not
      produce any alteration in cytochrome b5 level. Creatine kinase (CK) and alanine
      amino transferase (ALT) levels significantly increased on the 3rd d post
      treatment with enrofloxacin, but on the 6th d post-treatment with enrofloxacin
      the increase declined. Aspartate amino transferase (AST) significantly increased
      on the 6th d post enrofloxacin treatment. This study demonstrated the reversible
      competitive type of inhibition of enrofloxacin on CYP450 enzymes, and with
      coadministration with monensin produced increased CK, AST and ALT serum enzymes
      suggesting heart and liver injury. Simultaneous administration of enrofloxacin
      and monensin even at recommended levels could result in adverse interactions.

PMID- 15487644
TI  - Serum luteinizing hormone response to administration of gonadotropin-releasing
      hormone to atrazine-treated gilts.
AB  - The aim of the study was to evaluate the response of porcine luteinizing hormone
      (pLH) in serum to a single iv administration of gonadotropin-releasing hormone
      (GnRH) in atrazine-treated pigs. Experiments were performed in 15 mature female
      pigs (10 atrazine-treated, 5 control). From the onset of estrous (day 0), the
      pigs were given 1 mg atrazine/kg body mass in feed for 20 d of the estrous cycle.
      On the last day, blood samples were collected at min 0 from control and atrazine
      exposed, and 5 atrazine-exposed pigs were immediatey given 100 mg GnRH iv. Blood
      samples were collected from atrazine-exposed and the GnRH-injected atrazine
      exposed groups at 20, 30, 40 and 90 min and serum pLH concentrations were
      determined by radioimmunoassay. The administration of atrazine led to significant
      (p< 0.001) suppression of serum pLH concentrations (0.57 +/- 0.05 ng/ml) compared
      to control animals (2.24 +/- 0.20 ng/ml). The single iv GnRH administration to
      the atrazine-exposed pigs provoked significant pLH release at 20 and 30 min after
      GnRH administration, indicating attenuation of GnRH release in the atrazine
      exposed animals was responsible for the suppression of serum pLH.

PMID- 15487645
TI  - Safety of Pochonia chlamydosporia var catenulata in acute oral and dermal
      toxicity/pathogenicity evaluations in rats and rabbits.
AB  - The nematophagous fungus, Pochonia chlamydosporia var. catenulata (Kamyschlco ex
      Barron & Onions) Zare & W-Gams, was investigated as a potential biocontrol agent
      in integrated pest management strategy for Meloidogyne incognita (Kofoid and
      White) Chitwood in vegetable crops in Cuba. An acute oral and dermal
      toxicity/patogenicity study was performed to determine the safety of this fungus
      in non-target organisms. In the first study, a 1-dose level of 5 x 10(8) units of
      the microbial pest control agent/treated rat was used. Mortality or clinical
      signs were not evident and no adverse effects on body weight, hematology,
      microbiology and gross or microscopic pathology were observed. Food and water
      consumption was not significantly different between control and treated groups.
      In the acute dermal toxicity study, there was neither mortality nor clinical
      signs of toxicity, and no toxic effects in gross and microscopic pathology were
      detected. Thus, Pochonia chlamydosporia var. catenulate (Vcc-108, IMI SD 187),
      administered oral and dermally to rats and rabbits respectively, was safe in
      toxicity/pathogenicity studies.

PMID- 15487646
TI  - Dying to be thin: a dinitrophenol related fatality.
AB  - 2, 4-dinitrophenol (DNP) was originally used as an explosive and later introduced
      in the 1930's to stimulate metabolism and promote weight loss. It's also a
      component of pesticides still available globally. Concerns about hyperpyrexia
      lead to DNP being banned as a dietary aid in 1938. A 22-y-old male presented to
      the Emergency Department (ED) with a change in mental status 16 h after his last
      dose of DNP. On admission he was diaphoretic and febrile with an oral temperature
      of 102 F, but lucid and cooperative. He became agitated and delirious.
      Intravenous midazolam was initiated with mechanical cooling. Pancuronium was
      administered later and the patient was intubated. Over the next hour the patient
      became bradycardic, then asystolic, and despite resuscitative efforts, died.
      Advertisements claim DNP safe at the dose our patient ingested. It is widely
      available and with the potential to cause severe toxicity is an understudied
      public health concern.

PMID- 15487647
TI  - Acute lead intoxication in cattle housed in an old battery factory.
AB  - Six cows died 5 d after the owner put them in an old battery factory. The
      clinical symptoms were ataxia, blindness, rapid and difficult breathing,
      increased heart rate, tremors and coma. Necropsy was performed on 1 cow and
      pieces of metals were observed in the rumen. Serosal vessels of the rumen were
      hyperemic and slight fluid accumulation was observed in the abdominal cavity.
      Oedema was seen at the cerebrum. Severe necrosis and lipid accumulations were
      seen in the liver. All visceral organs were hyperemic. Zinc in the liver, kidney
      and lungs were 232, 103.5 and 97.3 ppm, respectively. Copper was 123.6 ppm in the
      liver 23.2 ppm in kidney and 11.8 ppm in lungs. The cadmium levels were normal,
      these were 66.7 ppm lead in liver, 80.5 ppm lead in kidneys and 35.8 ppm lead in
      lungs.

PMID- 15487649
TI  - Fatal paraquat poisoning in seven Portland, Oregon, dogs.
AB  - Paraquat is one of the few broad-spectrum herbicides available in the US;
      however, it is extremely toxic to companion animals when ingested. Despite its
      restricted use status, poisoning of dogs and cats remains relatively common. This
      clinical report documents a series of chronologically and geographically related
      cases of presumed malicious and fatal sub-acute paraquat poisoning in 7 dogs in
      Portland, OR. All animals developed acute gastrointestinal disturbance, renal
      compromise and insidiously progressive respiratory failure. Hyperlipasemia and
      moderate hypertension were notable featured in 5/7 cases. Trace levels of
      paraquat were demonstrated in the urine of 4/7 animals by gas-liquid
      chromatography/mass spectroscopy. Diagnosis in the remaining 3 cases was made
      through a combination of history or exposure, clinical signs and their
      progression, and pulmonary and renal histopathology.

PMID- 15487648
TI  - Fentanyl patch abuse: naloxone complications and extracorporeal membrane
      oxygenation rescue.
AB  - Fentanyl patches offer a novel, but increasingly common method of drug abuse. We
      describe a patient who developed severe respiratory dysfunction after fentanyl
      patch abuse via insufflation, naloxone administration and aspiration. After other
      aggressive interventions failed to correct worsening hypoxemia, extracorporeal
      membrane oxygenation (ECMO) was initiated and led to complete recovery. To our
      knowledge, this is the 1st reported case of ECMO being used to correct severe
      pulmonary dysfunction associated with opioid abuse. The risks associated with
      naloxone administration are discussed.

PMID- 15487650
TI  - Use of "Near Middle East Antivenom" to treat African bush viper envenomation.
AB  - Venom from an African bush viper is primarily hemotoxic and potentially life
      threatening. Existing, commercialy available antivenoms may not neutralize venom
      of this genus. A 25-y-old male was brought to the emergency room diaphoretic and
      hypotensive (70/40 mmHg) after a bite from a pet African bush viper. A puncture
      wound on the left thumb was leaking slightly, but there was no evidence of blood
      loss, edema or bruising. Approximately 100 min after exposure, the patient
      experienced a small amount of proximal swelling. Six h after envenomation, he was
      admitted to the intensive care unit for monitoring. At 10 h after the bite
      prothrombin time (PT > 100 sec) and international ratio (INR = 9.2) were
      elevated. The patient was unable to coagulate. He received fresh frozen plasma,
      cryoprecipitate, and Near Middle East Antivenom. Improvement in clinical status
      and laboratory parameters were observed after each of 3 doses of antivenom (d
      dimer > 1000 and fibrinogen = 137 mg/dL). The patient was monitored overnight,
      did not require additional antivenom and was discharged as laboratory parameters,
      vital signs and spread of the necrotic lesion stabilized. Near Middle East
      Antivenom appears effective in treatment of the hematologic sequelae secondary to
      African bush viper envenomation.

PMID- 15487651
TI  - Polymer fume fever-like syndrome due to hairspray inhalation.
AB  - Inhalation of fluoropolymer pyrolysis products causes a self-limited illness
      termed polymer fume fever; symptoms include fever, chills, myalgias and non
      productive cough, and are easily mistaken for an acute viral illness. We report a
      29-y-old male who developed fever and pneumonitis shortly after the inhalation of
      pyrolyzed hairspray. Chest x-rays showed pictures consistent with pneumonitis.
      The patient was treated solely with supplemental oxgen, and his symptoms resolved
      over 24 h. Inhalation of pyrolyzed hairspray may cause a syndrome resembling
      polymer fume fever.

PMID- 15487652
TI  - Fatal Vipera xanthina palestinae envenomation in 16 dogs.
AB  - Sixteen fatal dog envenomations by the snake Vipera palaestinae over a 14-y
      period are described. Most envenomations occurred during the late night hours in
      the warm months, and 8/16 dogs were bitten on the limbs. The most frequent
      clinical signs upon admission were soft tissue swelling and edema, local pain,
      depression, bleeding, lameness, dyspnea, and 6 dogs were in shock.
      Thrombocytopenia was present in 14/16 cases and increased hematocrit (13/16) and
      hemoglobin (9/16) concentration were the most common hematological abnormalities
      upon admission. Biochemical abnormalities included increased activities of muscle
      enzymes and alkaline phosphatase, hypocalcemia, and hypocholesterolemia. Creatine
      kinase activity was markedly increased in 2 dogs. During hospitalization serious
      complications in many dogs were disseminated intravascular coagulation, acute
      renal failure, seizures, cardiac arrhythmias, acute necrotizing pancreatitis and
      severe laryngeal edema; these required intensive and expensive therapies.
      Specific antivenin (10 ml) administered to 8/16 dogs did not prevent death.
      Glucocorticosteroids were given in 8 cases; however, their use was associated
      with complications. Four dogs suffered sudden death, 2 of which died 1-2 d after
      discharge. Necropsy performed on 3/16 dogs found soft tissue swelling and local
      bleeding at the envenomation sites as well as bleeding in several distal body
      organs and tissues.

PMID- 15487654
TI  - Anuric renal failure associated with zinc toxicosis in a dog.
AB  - The development of anuric renal failure associated with zinc intoxication was
      detected in a dog following ingestion of an ornamental brass knob from a toilet
      paper holder. The 3-y-old, male neutered, 15.4 kg Welsh Corgi presented to a
      local veterinary clinic with a 2-w history of intermittent vomiting, inappetance
      and lethargy. The dog was transferred to a veterinary teaching hospital where
      surgery was performed to remove the foreign body. The dogwas euthanized 24 h post
      surgery due to the development of anuric renal failure. Whole blood drawn at the
      time of surgery had a serum zinc concentration of 89.8 ppm (normal 0.7-2.0 ppm).
      The serum zinc concentration in this dog is the highest reported concentration in
      the literature. Ingestion of any zinc-containing metal object can potentially
      result in a severe intravascular hemolysis with subsequent renal impairment. Zinc
      intoxication should be suspected when hemolysis is accompanied by the finding of
      a metallic object in the gut.

PMID- 15487653
TI  - Diagnosis and treatment of zinc poisoning in a dog.
AB  - Acute zinc poisoning has been observed in dogs following the ingestion of
      metallic zinc objects. A 1 1/2-y-old female miniature bull terrier exhibiting
      anorexia, vomiting, depression, fever (39.9 C), icterus and intravascular
      hemolysis was diagnosed with acute zinc poisoning. Anemia, Heinz body production,
      azotemia and bilirubinemia were also evident. Abnormal pancreatic, hepatic and
      renal functions were also apparent. A radio opaque object was observed in the
      stomach. Based upon an elevated plasma zinc level of 28.6 ppm, a tentative
      diagnosis of zinc poisoning was made. Following surgical removal of the metallic
      zinc object, a blood transfusion and fluid therapy were given to restore the
      normal blood volume. Heparin, Cephazolin and Raniditine were also given, although
      chelation therapy was not provided. Zinc levels in the plasma declined in a
      steady fashion (half-life = 7.6 d). Complications, such as disseminated
      intravascular coagulation, chronic pancreatitis, renal or hepatic failure, were
      not observed. By 20 d post surgery, only mild elevation of liver enzymes was
      evident. Measurements of the half-life of zinc may provide a useful indication of
      prognosis and the success of treatment.

PMID- 15487655
TI  - Fatal yew (Taxus sp) poisoning in Willamette Valley, Oregon, horses.
AB  - Despite the well-founded reputation of plants of the genus Taxus as being amongst
      the most toxic plants for domestic livestock in the US, there are surprisingly
      few published case reports of yew poisoning in horses. This report documents 2
      acute fatalities in horses in the central Willamette Valley, OR associated with
      the consumption of Taxus sp. The predominant features of the intoxication were
      peracute death, with no signs of struggling or convulsions, in otherwise fit and
      well managed adult horses. The most significant gross necropsy findings were
      limited to pulmonary congestion and hemorrhage, suggestive of acute circulatory
      disturbance. A diagnosis of Taxus sp poisoning was confirmed on the basis of a
      history of potential exposure, by the identification of yew leaves in the gastric
      contents of the horses, and by the subsequent identification of yew clippings in
      the pasture. The literature relevant to Taxus sp poisoning in horses is reviewed.

PMID- 15487656
TI  - Life-threatening isopropyl alcohol intoxication: is hemodialysis really
      necessary?
AB  - Isopropyl alcohol (IPA) is widely used in industrial and home-cleaning products,
      easily available to general public and inexpensive: intoxications can occur
      unintentionally, in suicide attempts or by alcohol abusers as a substitute for
      ethanol. Symptoms involve the gastrointestinal tract, central nervous system and
      at high doses cardiovascular manifestations may appear. Ketonemia, ketonuria
      without hyperglicemia or acidosis and elevated osmol gap are common laboratory
      findings. Mortality and morbidity is low, but some fatal cases have been reported
      in patients in deep coma and especially those with hypotension. We present a life
      threatening intoxication, with deep coma and hypotension, treated successfully
      with hemodialysis. Whether hemodialysis must always be performed is a
      controversial question. Our opinion is hemodialysis is not needed, even in life
      threatening situations. Arguments about this opinion are presented.

PMID- 15487657
TI  - Can textbook covers be used to increase poison center utilization?
AB  - An education program was implemented at a regional poison center to increase use
      of a new nationwide 800 number (800/222-1222) in counties in our region that had
      low rates of utilization. We identified 10 counties with the lowest utilization
      rates and provided textbook covers to the elementary and secondary schools in
      these areas. The covers contained the poison help logo and information about what
      to do if a poisoning occurs. Changes in utilization rate for these counties were
      compared to similar counties over the course of a year. Utilization rates
      increased in both sets of counties over the study period, but there was no
      significant difference (p = 0.84) between the 2 groups. Use of textbook covers to
      increase awareness and utilization made little impact beyond our normal efforts
      and was not cost-effective.

PMID- 15487658
TI  - Lead in topsoil, hay, silage and blood of cows from farms near a former lead mine
      and current smelting plant before and after installation of filters.
AB  - This study covers 1975 to 2003 with measurements of lead in soil (n = 24), hay (n
      = 259), silage (n = 35) and blood of cows (n = 1279) from farms (n = 1 to 14)
      situated 1 to 10 km around a lead smelter. Until 1978, when protective filters
      were installed in the plant chimneys, the farms had been exposed to heavy
      industrial-metallurgic effluent. Early measurments (1968 to 1975) high lead (>
      600.0 mg lead/kg) in the topsoil, and continuing measurements (1981 to 2003)
      showed no significantly decreased lead after the installation of filters;
      however, mean lead in hay samples gradually decreased. In 1975 lead
      concentrations in 4 samples of hay were 227.0 to 953.0 mg/kg DM. In 2002 (n = 12)
      mean lead concentrations were about 100-fold lower (5.6 +/- 3.3 mg lead/kg DM). A
      similar trend of decreasing lead concentrations occurred also in the blood of
      cows. In 1975 (n = 9) average lead concentration was 1.2 +/- 0.6 mg/kg whole
      blood, while in 2002 (n = 58) it was about 20-times lower (0.07 +/- 0.005 mg/kg).
      This significant decrease in lead concentration may be attributed to sanitation
      of the major source of industrial emission of lead gasses and dust by
      installation of bag filters to the plant chimneys in 1978. After 1982 mean cow
      lead blood concentrations were within normal reference values (< 0.250 mg of
      lead/kg). However, during the last 10y mean lead concentrations have still been 1
      to 2-fold above the values measured in blood (n = 32) from 3 control areas in
      Slovenia. Cattle blood levels proved a good bioindicator of environmental
      contamination. Monitoring lead in the blood of animals on farms near the smelter
      should continue because the persistence of lead in topsoil is the main problem in
      this area.

PMID- 15487659
TI  - A professional hobby worth your time--newsletters!

PMID- 15487660
TI  - Fires and toxicology.

PMID- 15487661
TI  - An uncertain defense. How do you test that a human Ebola vaccine works? You
      don't.

PMID- 15487662
TI  - Readying for a relaunch. NASA makes the space shuttle safer but limits its
      missions.

PMID- 15487663
TI  - Transfer troubles. Cloning success in animals doesn't extend to humans.

PMID- 15487664
TI  - Heartbeat poetry. Verse speaks to matters of the heart-literally.

PMID- 15487665
TI  - Hawking a theory. Is the black hole information paradox solved?

PMID- 15487666
TI  - The service of siblings. Socially speaking, having brothers and sisters may be
      better than being an only child.

PMID- 15487667
TI  - Energy geopolitics. World power could shift if natural gas supplants oil.

PMID- 15487668
TI  - The myth is the message. Yet another discovery of the lost continent of Atlantis
      shows why science and myth make uneasy bedfellows.

PMID- 15487669
TI  - Father of spirit and opportunity. With the success of twin rovers on the Red
      Planet, Steven W. Squyres and his team are showing how to conduct robotic
      missions--and setting the stage for human exploration.

PMID- 15487670
TI  - A universe of disks.

PMID- 15487671
TI  - The hidden genetic program of complex organisms.

PMID- 15487672
TI  - Controlling hurricanes.

PMID- 15487673
TI  - The Internet of things.

PMID- 15487675
TI  - Fixing the vote.

PMID- 15487674
TI  - Dying to see.

PMID- 15487677
TI  - Earthquake protection. Shock absorbed.

PMID- 15487676
TI  - Hitting the genetic off switch.

PMID- 15487678
TI  - Gadget envy. All-in-one cell phones can do just about anything.

PMID- 15487679
TI  - Finnish research programme on environmental health 1998--2001.

PMID- 15487680
TI  - Consortium on urban air particles and environmental health.

PMID- 15487681
TI  - Exposure assessment of ultrafine particles in epidemiologic time-series studies.
AB  - The health effects of fine-particulate air pollution (PM2.5, aerodynamic diameter
      <2.5 microm) observed in epidemiologic time-series studies may partly be due to
      the high number concentration of ultrafine particles (aerodynamic diameter <0.1
      microm) in urban air. The key uncertainty is how well daily variations in the
      ultrafine particle concentration measured at a central site correlate with the
      variations in average personal exposure. Due to a lack of research data, this
      correlation has been estimated indirectly in this review on the basis of studies
      on the sources, ambient air levels, spatial variability, indoor air levels, and
      lung deposition of ultrafine particles. It is concluded that central site
      monitoring may give a somewhat worse proxy for human exposure to ultrafine
      particles than to PM2.5 in time-series studies.

PMID- 15487682
TI  - Mortality and air pollution in metropolitan Helsinki, 1988--1996.
AB  - OBJECTIVES: The daily respiratory, cardiovascular, and total mortality of the
      population in the subarctic climate of the Helsinki metropolitan area was
      analyzed for associations with daily variations in concentrations of common
      ambient-air pollutants. METHODS: The associations between daily mortality and the
      ambient-air concentrations of ozone (O3), nitrogen dioxide (NO2), carbon monoxide
      (CO), sulfur dioxide (SO2), total suspended particulate matter (TSP), and
      particulate matter with an aerodynamic diameter of <10 microm (PM10) in 1988-
      1996 were analyzed with Poisson regression in a generalized linear model.
      Specifically, the differences for combustion and noncombustion particulate matter
      were determined using the blackness of the TSP filters as a surrogate for mostly
      traffic-derived combustion particles. Total mortality was analyzed according to
      three age groups (15-64, 65-74, > or =75 years) of the population. RESULTS:
      Significant associations consistent across lag times and age groups were found
      between spring and summer O3 levels and respiratory (4.30% increase per 10
      microg/m3 of the 4-day mean O3 level) and total (2.42% increase per 10 microg/m3
      of the 4-day mean O3 level) mortality. PM10 was consistently associated with
      respiratory mortality across the lag times and age groups (3.96% increase per 10
      microg/m3 of PM10 at lag-time 1). When adjusted for TSP concentration, the
      blackness of the TSP was significantly associated with total mortality (2.06% per
      10(-5) units, 95% confidence interval 0.09-4.06) at lag time 1, but not at the
      other lag times. CONCLUSIONS: These results provide additional evidence of an
      association between summertime O3 concentrations and mortality. They also support
      the findings of previous studies indicating that coarse mineral particles are not
      as strongly associated with mortality as fine, combustion-derived particles are.

PMID- 15487683
TI  - Resuspended dust episodes as an urban air-quality problem in subarctic regions.
AB  - OBJECTIVES: This paper describes the resuspension of road dust in an urban
      subarctic environment and focuses especially on the effect of wind speed on the
      formation of resuspended dust episodes. METHODS: The study was conducted in
      Kuopio, Finland, in the spring of 1995. There were 36 daily measurements of mass
      concentrations of fine particulate matter (PM2.5), thoracic particulate matter
      (PM10), total suspended particulate matter, black carbon and carbon monoxide;
      size-segregated number concentrations of particles (diameter range 0.01-10
      microm); and meteorological parameters. Total elemental compositions of PM2.5 and
      PM10 samples were analyzed with inductively coupled plasma mass spectrometry.
      RESULTS: The mass and number concentrations of particles in all the size ranges
      and the concentrations of soil-derived (iron) and combustion-derived (vanadium
      and lead) elements in the PM2.5 and PM10 increased during the dust episodes. The
      daily average wind speed dually affected the episodes. The pollutant
      concentrations increased at wind speeds of <4 m/s and >5 m/s. The former was
      related to inversion-type conditions characterized by low wind speeds, while the
      latter was likely to be due to wind-blown resuspended dust. Resuspended lead
      accounted for an average of 27% of the total lead, and resuspended vanadium for
      46% of the total vanadium in PM2.5. CONCLUSIONS: Resuspended dust episodes were
      related to both low and high wind speeds, and the relationship suggests that
      factors other than wind speed, such as turbulence induced by traffic, affect the
      emergence of such episodes. The contribution of elevated levels of crustal
      material and toxic metals in resuspended PM2.5 to human adverse health effects
      should be investigated.

PMID- 15487684
TI  - Sources of fine particulate matter in personal exposures and residential indoor,
      residential outdoor and workplace microenvironments in the Helsinki phase of the
      EXPOLIS study.
AB  - OBJECTIVES: This study assessed the source contributions to the mass
      concentrations of fine particles (PM2.5) in personal exposures and in residential
      indoor, residential outdoor, and workplace indoor microenvironments of the
      nonsmoking adult population unexposed to environmental tobacco smoke in Helsinki,
      Finland. METHODS: The elemental composition of 48-hour personal exposure and
      residential indoor, residential outdoor, and workplace indoor PM2.5 was analyzed
      by energy-dispersive X-ray fluorescence spectrometry for 76 participants not
      exposed to environmental tobacco smoke and 102 participating residences with no
      smoking in Helsinki as a part of the EXPOLIS study. Subsequently, a principal
      component analysis was used to identify the emission sources of PM2.5-bound
      elements and black smoke in each microenvironment, and this information was used
      to identify the corresponding sources in personal exposures. Finally, source
      reconstruction was done to determine the relative contributions of each source
      type to the total PM2.5 mass concentrations. RESULTS: Inorganic secondary
      particles, primary combustion, and soil were the dominant source types for the
      PM2.5 mass concentration in all the microenvironments and personal exposures. The
      ratio of the residential indoor-to-outdoor PM2.5 concentration was close to
      unity, but the corresponding elemental ratios and source contributions varied.
      Resuspension of soil dust tracked indoors was a much larger contributor to
      residential and workplace indoor PM2.5 than soil dust to residential outdoor
      PM2.5. Source contributions to personal PM2.5 exposures were best approximated by
      data from residential and workplace indoor microenvironments. CONCLUSIONS:
      Population exposure assessment of PM2.5, based on outdoor fixed-site monitoring,
      overestimates exposures to outdoor sources like traffic and long-range transport
      and does not account for the contribution of significant indoor sources.

PMID- 15487685
TI  - Statistical model for assessing the portion of fine particulate matter
      transported regionally and long range to urban air.
AB  - OBJECTIVES: This study attempted to develop a simple statistical model for
      assessing the contribution of aerosols transported regionally and those
      transported long range to the concentrations of fine particulate matter (PM2.5)
      in urban air in Helsinki. METHODS: The construction and testing of the linear
      regression model was based on PM2.5 measurement data from two locations in the
      City of Helsinki (Vallila & Kallio) and on ion concentration data obtained from
      the three nearest monitoring stations of The Co-operative Programme for
      Monitoring and Evaluating of the Long-range Transmission of Air Pollutants in
      Europe (EMEP). The "ion sum" was calculated on the basis of the following daily
      measured EMEP parameters in 1998--2000: (i) sulfate (SO4(2-)), (ii) the sum of
      nitrate (NO3-) and nitrogen acid (HNO3), and (iii) the sum of ammonium (NH4+) and
      ammonia (NH3). The ion sum was compared with sulfate as the proxy variable for
      PM2.5 transported long range. RESULTS: The correlation of the daily average PM2.5
      concentration with the ion sum (R2=0.59-0.61) was higher than that with sulfate
      (R2 = 0.48-0.50). The regression estimates showed relatively small year-to-year
      variation. The contribution of long-range transport to the measured PM2.5
      concentration in urban air in Helsinki was estimated to be 64-76%. CONCLUSIONS:
      The results showed a strong association between the ion sum interpolated from the
      EMEP data and the PM2.5 concentration measured at urban sites in Helsinki. This
      association can be utilized in local dispersion modeling of the PM2.5
      concentration in urban air.

PMID- 15487686
TI  - Particle size characterization and the indoor-to-outdoor relationship of
      atmospheric aerosols in Helsinki.
AB  - OBJECTIVES: The influence of traffic and meteorological conditions on aerosol
      characteristics outdoors, the relationship between indoor and outdoor aerosol
      particles, and the pollutant transport indoors by means of a mechanical
      ventilation system were studied. METHODS: Indoor and outdoor concentrations of
      fine-particle numbers were measured during the summer (15 May--30 June 2000) in
      one office located in the basement of a building in Helsinki, Finland. The total
      number concentration was measured with a condensation particle counter, and the
      particle number size distribution (7-600 nm) was measured with a differential
      mobility particle sizer. The size distribution (0.3-25 microm) of the indoor
      particle numbers was periodically measured with a laser particle counter.
      RESULTS: Meteorological conditions, especially wind direction, had the greatest
      effect on the total number concentration and the size distribution of aerosol
      particles outdoors. The outdoor number concentration of ultrafine particles
      (diameter <100 nm) was strongly dependent on traffic density. The temporal
      variations in the indoor number concentration of ultrafine and fine particles (7
      600 nm) closely followed the corresponding temporal variations outdoors. The
      building ventilation system was the main means of transporting aerosols indoors.
      The mean penetration factor was 0.41 (SD 0.11) for the nucleation mode (7-25 nm),
      0.74 (SD 0.09) for the Aitken mode (25-100 nm), and 0.87 (SD 0.06) for the
      accumulation mode (100-600 nm). CONCLUSIONS: The ultrafine particles were bimodal
      with a nucleation mode (particle diameter <25 nm) and an Aitken mode (25 nm
      <particle diameter <100 nm). An accumulation mode was observed with a particle
      diameter larger than 100 nm. The patterns of fine-particulate air pollution
      inside an office can be largely estimated on the basis of the outdoor aerosol
      characterization and the mechanical ventilation system.

PMID- 15487687
TI  - A sectional aerosol model for submicron particles in indoor air.
AB  - OBJECTIVES: This study attempted to simulate indoor concentrations and the indoor
      to-outdoor (I:O) number concentration ratios of aerosol particles in the
      submicron size range. METHODS: The developed model used size-segregated outdoor
      number concentrations of particles as inputs and produced the indoor aerosol size
      spectrum. It covered all the major dynamic processes associated with the indoor
      aerosol concentration: transport and filtration in the air exchange system,
      deposition, coagulation, nucleation, condensation, and indoor sources. The model
      results were compared with measured particle concentrations. Numerous sensitivity
      analyses were also made for testing the effect of different dynamic processes on
      the model results. No indoor particle sources were considered in the sensitivity
      simulations. RESULTS: Changes in the air exchange rate had the strongest effect
      on the simulated I:O ratios of particle number concentrations. Filtration in the
      air exchange system also had a large effect on the indoor concentrations.
      Deposition did not significantly change the particle number concentrations within
      a realistic range of turbulence intensity indoors and the temperature differences
      between the ambient air and surfaces. Coagulation affected only the smallest
      particle size ranges. Condensation and nucleation had potentially large effects
      on the particle size spectrum. CONCLUSIONS: The model reproduced the measured I:O
      ratios of fine and ultrafine particle concentrations with reasonable accuracy.
      The model can be a valuable tool with which to estimate the I:O ratios for human
      exposure assessment.

PMID- 15487688
TI  - Theoretical analysis of the influence of aerosol size distribution and physical
      activity on particle deposition pattern in human lungs.
AB  - OBJECTIVES: A theoretical comparison of modeled particle depositions in the human
      respiratory tract was performed by taking into account different particle number
      and mass size distributions and physical activity in an urban environment.
      METHODS: Urban-air data on particulate concentrations in the size range 10 nm-10
      microm were used to estimate the hourly average particle number and mass size
      distribution functions. The functions were then combined with the deposition
      probability functions obtained from a computerized ICRP 66 deposition model of
      the International Commission on Radiological Protection to calculate the numbers
      and masses of particles deposited in five regions of the respiratory tract of a
      male adult. The man's physical activity and minute ventilation during the day
      were taken into account in the calculations. RESULTS: Two different mass and
      number size distributions of aerosol particles with equal (computed) <10 microm
      particle mass concentrations gave clearly different deposition patterns in the
      central and peripheral regions of the human respiratory tract. The deposited
      particle numbers and masses were much higher during the day (0700-1900) than
      during the night (1900-0700) because an increase in physical activity and
      ventilation were temporally associated with highly increased traffic-derived
      particles in urban outdoor air. CONCLUSIONS: In future analyses of the short-term
      associations between particulate air pollution and health, it would not only be
      important to take into account the outdoor-to-indoor penetration of different
      particle sizes and human time-activity patterns, but also actual lung deposition
      patterns and physical activity in significant microenvironments.

PMID- 15487689
TI  - Chemical and in vitro toxicologic characterization of wintertime and springtime
      urban-air particles with an aerodynamic diameter below 10 microm in Helsinki.
AB  - OBJECTIVES: The chemical composition and toxicity of wintertime urban-air
      particulate matter with an aerodynamic diameter of <10 microm (PM10), derived
      mostly from long-range transport and local combustion sources, were compared with
      those of springtime PM10 derived mostly from the resuspension of road dust.
      METHODS: Water-soluble ions and elements and polycyclic aromatic hydrocarbons
      (PAH) were analyzed from seasonally pooled PM10 samples collected at a busy
      traffic site in Helsinki in 1999. These PM10 samples were also tested for
      cytotoxicity [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide test]
      and the production of proinflammatory cytokines [tumor necrosis factor alpha (TNF
      alpha) and interleukin 6 (IL-6)] and nitric oxide (NO) in the mouse macrophage
      cell line RAW 264.7. Their oxidative capacity and the associated DNA
      (deoxyribonucleic acid) damage were investigated by electron paramagnetic
      resonance and the formation of 8-hydroxy-2'-deoxyguanosine (8-OH-DG) in isolated
      calf thymus DNA, respectively. RESULTS: The late wintertime and springtime PM10
      had similar compositions of water-soluble ions and elements, but the winter PM10
      had a higher content of PAH. The spring PM10 was a much more potent inducer of
      TNF-alpha and IL-6 production than the winter PM10 was, but there were no
      consistent differences in cytotoxic potency. In contrast, the winter PM10 was a
      significantly more potent inducer of NO production and 8-OH-DG formation. The
      large cytokine responses to the spring PM10 were caused by its insoluble fraction
      and largely inhibited by the endotoxin antagonist polymyxin B. The transition
      metal chelator deferoxamine did not modify the proinflammatory or cytotoxic
      responses to the PM10 samples. CONCLUSIONS: The toxicity profile of urban-air
      PM10 changed with season in a subarctic climate. Particulate-bound endotoxin from
      soil gram-negative bacteria is suggested as a highly proinflammatory constituent
      of springtime resuspended road dust.

PMID- 15487690
TI  - Effect of the shape of mica particles on the production of tumor necrosis factor
      alpha in mouse macrophages.
AB  - OBJECTIVES: Micas are thin, sheetlike minerals that are abundant in rocks and
      sand. They are common components of resuspended road dust in spring in Finland.
      The proinflammatory potential of mica particles was studied. METHODS: Respirable
      size particles were prepared from phlogopite mica either by milling (milled
      phlogopite) or water elutriation (elutriated phlogopite). The cations were
      extracted with acids from one phlogopite sample (acid-treated phlogopite).
      Minusil (alpha-quartz) and titanium dioxide were used as positive and negative
      controls, respectively. Cultured mouse macrophage cells (RAW264.7) were exposed
      for 24 hours to the mineral particles at concentrations between 10 and 500
      microg/ml. The mineral particle concentration of 100 microg/ml and the time range
      from 3 to 48 hours were used to study the time-dependency of the responses. Cell
      viability and the production of nitric oxide and proinflammatory cytokines
      [interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha)] were studied in
      the macrophages. RESULTS: Elutriated phlogopite particles were larger, and they
      had a smaller surface area and a more regular, plate-like shape than milled
      phlogopite. The mineral particles showed the following order of potency to induce
      TNF-alpha production in macrophages: elutriated phlogopite > Minusil > acid
      treated phlogopite > milled phlogopite > titanium dioxide. Only elutriated
      phlogopite induced a small, dose-dependent IL-6 response. The mineral particle
      samples did not induce nitric oxide production in the macrophages. CONCLUSIONS:
      Phlogopite mica stimulates macrophages to produce proinflammatory cytokines. The
      platelike shape of mica particles rather than surface area seems to be important
      for cytokine production.

PMID- 15487691
TI  - Diabetic retinopathy--an historical review.
AB  - Diabetic macular changes in the form of yellowish spots and extravasations that
      permeated part or the whole thickness of the retina were observed for the first
      time by Eduard Jaeger in 1856. This was only possible as a result of the newly
      developed direct ophthalmoscope that was first described in 1855. Jaeger's
      findings were controversial at the time and Albrecht von Graefe openly claimed
      that there was no proof of a causal relationship between diabetes and retinal
      complications. It was only in 1872 that Edward Nettleship published his seminal
      paper "On oedema or cystic disease of the retina" providing the first
      histopathological proof of "cystoid degeneration of the macula" in patients with
      diabetes. In 1876, Wilhelm Manz described the proliferative changes occurring in
      diabetic retinopathy and the importance of tractional retinal detachments and
      vitreous haemorrhages. In the early years of the 20th century, the debate
      continued whether macular changes were directly related to diabetes or whether
      they were due to hypertension and arteriosclerosis. It was not until the second
      half of the century that the work of Arthur James Ballantyne in Glasgow provided
      more evidence that suggested that diabetic retinopathy represents a unique
      vasculopathy.

PMID- 15487692
TI  - Theoretical bases of non-ophthalmoscopically visible endpoint photocoagulation.
AB  - Laser photocoagulation is a photothermal process in which heat is produced by the
      absorption of laser energy by targeted tissues. The purpose of the treatment is
      to induce thermal therapeutic damage, which causes biological reactions and
      ultimately beneficial effects. The current endpoint of laser photocoagulation of
      the chorioretina is an ophthalmoscopically visible retinal whitening. Retinal
      blanching is the sign that the retina itself has been thermally damaged and
      results in a number of undesired adverse events. The mechanisms underpinning the
      efficacy of laser photocoagulation are still poorly understood. However, recent
      hypotheses postulate that full thickness retinal damage may not be needed to
      obtain beneficial therapeutic effectiveness. Preliminary studies with laser
      photocoagulation on animals demonstrated the ability to create therapeutic
      lesions confined around the Retinal Pigment Epithelium (RPE) cells without
      causing apparent damage to the overlying retina. The laser impacts were not
      visible by slit lamp biomicroscopy at the time of laser delivery. Recent
      experiments showed that the beneficial effect of retinal photocoagulation is
      mediated by factors derived from the RPE. Non Ophthalmoscopically Visible
      Endpoint Photocoagulation (NOVEP) protocols might allow treatments that confine
      minimal therapeutic damage around the cells of the RPE and minimize the damage to
      the neurosensory retina.

PMID- 15487693
TI  - Light panretinal photocoagulation (LPRP) versus classic panretinal
      photocoagulation (CPRP) in proliferative diabetic retinopathy.
AB  - PURPOSE: We misled to verify whether a panretinal photocoagulation (PRP)
      performed using low levels of ARGON laser energy (light PRP) has the same
      efficacy as a PRP performed in a conventional fashion using argon green
      wavelengths (classic PRP) in eyes with high-risk proliferative diabetic
      retinopathy (HRPDR). Furthermore, we misled to compare the session number
      performed and the side effects produced by the two techniques. METHODS: Sixty
      five eyes with HRPDR of 50 consecutive patients were enrolled in a prospective
      randomized controlled trial. In eyes selected for light PRP, a very light
      biomicroscopic effect on the retina was obtained for each spot. In eyes assigned
      to classic PRP, each spot produced a white-yellow biomicroscopic effect. Mean
      follow-up was 22.4 months +/- 9.7 in the light PRP and 21.6 months +/- 9.3 in the
      classic PRP group (p = 0.727). RESULTS: The initial mean logMAR visual acuity
      (VA) in the light PRP group was 0.12 +/- 0.13 and in the classic PRP group 0.14
      +/- 0.15 (p = 0.493). The final mean VA in the former was 0.18 +/- 0.25, and in
      the latter 0.27 +/- 0.30 (p = 0.231). Median power was 235mW (100-540mW) for
      light and 420mW (200-950mW) for classic PRP (p < 0.001). Regression of HRPDR at
      the end of the follow-up was obtained in 30/31 eyes (97%) treated with classic
      PRP and in 31/34 eyes (91%) treated with light PRP (p = 0.615). The total mean
      session number was 7.4 +/- 2.4 for light and 9.9 +/- 2.2 for the classic PRP
      group (p < 0.001). Complications were more frequent in the classic PRP group.
      CONCLUSIONS: The efficacy of Light PRP is similar to that of classic Light PRP in
      eyes with HRPDR. Light PRP is associated with fewer complications and allows the
      reduction of the number of treatment sessions.

PMID- 15487694
TI  - Infrared micropulsed laser treatment for diabetic macular edema--subthreshold
      versus threshold lesions.
AB  - PURPOSE: To assess the effectiveness of subthreshold (invisible after placement)
      and threshold (barely visible after placement) 810nm laser photocoagulation in
      the treatment of clinically significant diabetic macular edema. METHODS: A grid
      of subthreshold laser spots was used to treat patients with diabetic edema.
      Retrospectively, the results of treatment of 20 eyes of 20 patients were compared
      to the results of treatment of 120 eyes of 120 patients using a grid of threshold
      laser lesions. RESULTS: At six months, 60% of subthreshold treated eyes and 75%
      of threshold treated eyes showed anatomic resolution of macular edema.
      Improvement or stabilization of visual acuity was achieved in 85% of threshold or
      subthreshold treated eyes. CONCLUSION: Gentle grid treatment of regions of
      diabetic macular edema was effective in ameliorating the edema and limiting
      visual loss. Subthreshold laser was less effective in promoting resolution of
      edema compared to threshold lesions, though the difference was not significant in
      this instance.

PMID- 15487695
TI  - Minimal intensity diode laser (810 nanometer) photocoagulation (MIP) for diffuse
      diabetic macular edema (DDME).
AB  - BACKGROUND AND OBJECTIVE: To determine the effectiveness of minimal intensity
      diode laser (810nm) photocoagulation (MIP) for diffuse diabetic macular edema
      (DDME). METHODS: Patients demonstrating diffuse diabetic macular edema (DDME)
      were treated with minimal intensity diode 810 laser photocoagulation or modified
      grid photocoagulation consecutively. Patients were seen and reevaluated at
      regular follow up visits every 3 to 4 months and retreated if residual diffuse
      diabetic macular edema was still present. Selected patients were tested with
      Goldmann visual field, pre and post-treatment. Visual improvement, visual loss,
      visual field, reduction/elimination of macular edema, and a number of treatments
      were studied. RESULTS: Reduction/elimination of DDME was observed in
      approximately 74% of eyes with 24 months follow up. The number of treatments per
      eye ranged from 1 to 5. The presence of cystoid macular edema, initial poor
      visual acuity, the presence of coexisting macular ischemia, or a history of
      systemic hypertension did not effect the outcome. Patients without a history of
      systemic vascular disease had a better chance of visual stabilization or
      improvement compared to those patients with a history of systemic vascular
      disease. Eighty-eight percent of patients had at least stable visual acuity at
      the last follow up visit. No post-treatment subjective complaints of increased
      pericentral scotomas were encountered in this group of patients and post
      treatment atrophic scarring was substantially reduced, by using minimal intensity
      diode laser 810 photocoagulation, compared to eyes previously treated with
      shorter wavelengths and more visible burns. CONCLUSION: Minimal intensity diode
      laser 810nm modified grid laser photocoagulation for diffuse diabetic macular
      edema (DDME) is effective in reducing/eliminating DDME, although resolution of
      edema may be slightly prolonged and may require 1 or 2 additional treatments
      compared to eyes previously treated with shorter wavelengths and more visible
      burns. However, this method appears to be advantageous in that it appears to
      reduce the objective and subjective effect on the pericentral visual field, as
      well as substantially reducing the post-treatment atrophic scarring seen in
      patients treated with shorter wavelength lasers and move visible burns.

PMID- 15487696
TI  - Progress in vitreoretinal surgery for proliferative diabetic retinopathy.

PMID- 15487697
TI  - Genetics of diabetic retinopathy.

PMID- 15487698
TI  - Interpreting mercury in blood and urine of individual patients.
AB  - The effects of mercury exposure are determined by: (a) chemical form, (b) route
      of exposure, (c) dose, and (d) patient factors. Patient factors include age,
      genetics, environmental aspects, and nutritional status, and are responsible for
      different individual responses to similar doses. When blood and urine are
      collected to evaluate exposure, the results are influenced by (a) specimen
      collection, (b) analysis, and (c) the time elapsed from exposure. Interpretation
      is influenced by the patient's symptoms and is facilitated by comparison to
      published reports. The ranges reported in the literature are broad, with
      elevations as high as 16,000 microg/L in blood and 11,000 microg/L in urine.
      Interpretation is relatively straightforward when the results are massively
      elevated, but becomes increasingly difficult as concentrations approach the
      population norms (blood and urine mercury < 10-20 microg/L). Interpretation can
      be aided by biological markers (eg, urine porphyrins, beta2-microglobulin, and N
      acetyl-beta-D-glucosaminidase).

PMID- 15487699
TI  - Morphoproteomic and pharmacoproteomic correlates in hormone-receptor-negative
      breast carcinoma cell lines.
AB  - The aim of this study was to elucidate protein circuitry in breast cancer based
      on the profiling of hormone-receptor-negative breast carcinomas using
      morphoproteomic and pharmacoproteomic techniques. Three human breast carcinoma
      cell lines (SKBR-3, MDA-175, MDA-231) were reacted by immunohistochemical (IHC)
      procedures to detect several categories of protein analytes. Immunoreactivities
      and cell compartmentalizations were scored from 0 to 3+ positivity using bright
      field microscopy. An automated cellular imaging system (ACIS) was used to obtain
      a final combined score of staining intensity and positive cells in the IHC
      reactions, to enable comparisons with the visual scores and the rates of
      inhibition by pharmaceutical agents. FDA-approved inhibitors that target the
      protein circuitry were added to the cultures for 2-4 days. Proliferation assays
      were conducted, and in vitro inhibition rates were calculated as (control -
      treated)/control. Western blot analyses of whole cell lysates assessed the
      effects of the pharmaceutical agents on selected aspects of protein circuitry.
      Good to excellent correlation was observed between visual scores and ACIS scores
      (r values from 0.732 to 0.996 in 10 of 11 trials). Gleevec produced growth
      inhibition that correlated with the composite expressions of the platelet-derived
      growth factor (PDGF) family of ligands and receptors; captopril inhibited only
      MDA-175, consistent with its unique expression of plasmalemmal angiotensin
      converting enzyme (ACE); and interferon (IFN)-alpha effected growth inhibition in
      accordance with the degree of conventional (c) protein kinase C (PKC)-alpha and
      phosphorylated (p)-PKCalpha/betaII expressions. Western blot analyses revealed
      correlative changes of several intracellular signals following incubation with
      these inhibitors. This study shows (a) a close association between the
      immunohistochemical expression of signal transduction markers and in vitro
      inhibition by pharmaceutical agents, and (b) correlations between the sites of
      action of the pharmaceutical agents and the downstream expression of proteins in
      hormone-receptor-negative breast cancer cell lines. Such morphoproteomic and
      pharmacoproteomic profiling of individual tumors may enable the pathologist and
      oncologist to design antitumor therapy that is customized for an individual
      patient.

PMID- 15487700
TI  - Pamidronate resistance and associated low ras levels in breast cancer cells: a
      role for combinatorial therapy.
AB  - To identify markers sensitive to inhibitors of the farnesylation pathway, we used
      3 breast cancer cell lines (SKBR-3, MDA-175, and MDA-231) to evaluate the in
      vitro effects of pamidronate, an inhibitor of farnesyl diphosphate synthase. In
      response to pamidronate, there was significant inhibition of cell proliferation
      in MDA-231 and SKBR-3 cells, compared to MDA-175 cells. This correlated with
      their respective basal levels of N-ras and H-ras. N-ras and H-ras protein levels
      were both reduced in MDA-231 cells, and to lesser extent in SKBR-3 cells,
      following exposure to pamidronate, whereas these markers were not altered in MDA
      175 cells. Combinatorial therapy with pamidronate and Gleevec, an inhibitor of
      several tyrosine kinases; Velcade, a proteasome inhibitor; or rapamycin, an
      inhibitor of the mammalian target of rapamycin (m-TOR) all showed additive
      effects in causing proliferative inhibition in MDA-175 cells. In summary,
      resistance to pamidronate may result from low levels of GTPase-activating
      proteins, such as N-ras and H-ras, in tumor cells. Combinatorial therapies
      directed against other signaling pathways, not dependent upon ras, may be
      required to overcome such resistance.

PMID- 15487701
TI  - Arsenic trioxide (As2O3) sensitivity of carcinoma cell lines and cancer cells
      from patients with carcinomatosis peritonei.
AB  - The effectiveness of As2O3 treatment was studied in 3 carcinoma cell lines, LoVo,
      OVCAR-3, and PA-1, and in cancer cells obtained from ascites fluids of 8 patients
      with carcinomatosis peritonei. LoVo, OVCAR-3, and PA-1 cell lines, and cancer
      cells from the patients were cultured in As2O3 gradient media; As2O3 sensitivity
      was evaluated by trypan blue dye exclusion and by morphologic examination after
      Wright staining. PA-1 was the most sensitive cell line to As2O3; OVCAR-3 and LoVo
      were resistant to As2O3. Cancer cells from 2 of 8 patients were sensitive to
      As2O3. The in vivo tumoricidal effect of As2O3 (100 microg/day, i.p.) was studied
      in 30 BALB/c nude mice following i.p. implantation of PA-1 tumor cells. The 17
      As2O3-injected mice died of extensive intratumoral hemorrhage, necrosis, and
      hemorrhagic ascites within 48 hr after initial treatment. In 10 As2O3-untreated
      tumor-bearing control mice, only focal intratumoral hemorrhage and necrosis were
      noted. In summary, solid tumor cell lines and cancer cells from patients showed
      various As2O3 sensitivities in vitro, and As2O3 had a marked tumoricidal effect
      on PA-1 cells in vivo. These results suggest that As2O3 treatment might possibly
      be beneficial in patients with carcinomatosis peritonei who are resistant to
      conventional therapy and whose tumors show in vitro sensitivity to As2O3.
      However, to minimize the life-threatening tumor lysis effect, it would be better
      to administer As2O3 after removal of the peritoneal tumor masses.

PMID- 15487702
TI  - Angiotensin II regulation of TGF-beta in murine mesangial cells involves both PI3
      kinase and MAP kinase.
AB  - INTRODUCTION: Chronic activation of the angiotensin II (AngII) type 1 receptor
      (AT-1) is a central event in the development of chronic kidney disease (CKD), in
      part through enhanced expression of TGF-beta, and AT-1 receptor blockade inhibits
      the progression to CKD in a variety of disease states. The AT-1 receptor is a
      heptahelical Gaq/11-coupled receptor that initiates phospholipase C activity and
      release of intracellular calcium; recent data suggest that the AT-1 receptor can
      also activate the epidermal growth factor receptor (EGFR), although the roles of
      specific EGF-mediated signaling cascades in AT-1 effects on mesangial cell
      biology are uncertain. We hypothesized that 2 EGFR-activated pathways, PI3 kinase
      and MAP kinase, are stimulated by the AT-1 receptor and, in part, regulate the
      effects of AngII on TGF-beta1 levels in mesangial cells. METHODS: We examined the
      effects of AT-1 receptor activation on EGFR, PI3 kinase, and MAP kinase
      activation in murine mesangial cells. Upon achieving 60-80% confluence, the
      medium was changed to low-serum for 48 hr and cells were exposed to either the AT
      1 receptor blocker, losartan, the EGFR blocker, AG1478, or control medium, and
      then stimulated with AngII. Similar experiments were performed using LY294002 and
      U0126, specific inhibitors of PI3 kinase and MEK, respectively. Total cellular
      protein lysates and RNA were isolated. Activation of the receptors and pathways
      was evaluated by immunoblotting and levels of TGF-beta mRNA were measured using
      real-time quantitative RT-PCR. RESULTS: AngII induced autophosphorylation of EGFR
      (pY1068) and activated Akt and ERK, downstream targets of PI3 kinase and MAP
      kinase, respectively. AngII-mediated EGFR autophosphorylation was inhibited by
      losartan and AG1478. AG1478 also inhibited both basal and AngII-mediated
      activation of Akt and ERK. Finally, AngII-mediated increase in TGF-beta mRNA was
      inhibited by losartan, AG1478, LY249002, and U0126. CONCLUSIONS: Stimulation of
      the AT-1 receptor in murine mesangial cells results in activation of the EGF
      receptor with subsequent signaling through PI3 kinase and MAP kinase, thereby
      regulating TGF-beta mRNA levels. These data suggest that AT-1 receptor signaling
      pathways through EGFR may serve as a therapeutic target to inhibit the
      development of CKD.

PMID- 15487703
TI  - Degradation of pre-beta-high density lipoproteins and their binding activity to
      human blood monocytes.
AB  - We have previously reported that high density lipoprotein3 (HDL3), apolipoprotein
      A-I (apoA-I) rich lipoprotein, binds specifically to the surface of human blood
      monocytes. Pre-beta-HDL with a pre-beta mobility on agarose gels is an apoA-I (MW
      28 kDa)-rich and a lipid-poor lipoprotein. In the present study, we found that
      pre-beta-HDL purified by ion-exchange chromatography was susceptible to
      degradation if isolated in the absence of anti-proteases, resulting in the
      smaller lyso-pre-beta-HDL. The mass of lyso-pre-beta-HDL was confirmed using a
      delayed extraction matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (DE-MALDI-TOF MS), which showed a fragment of approximately
      22,378.9 Da. We further investigated limited proteolysis of apo A-I purified from
      human plasma HDL with various proteases, and cleavage appeared to be limited to
      the C-terminal end of apo A-I (amino acids 188-223). The ability of pre-beta-HDL
      and lyso-pre-beta-HDL to compete for HDL binding to monocytes was determined
      using a flow cytometry-based assay. Pre-beta-HDL competed efficiently for binding
      whereas lyso-pre-beta-HDL was significantly less effective. The data may indicate
      that the binding sites on monocytes specifically recognize apoA-I. We suggest
      that limited proteolysis around amino acids 188-223 of apo A-I may affect lipid
      binding, which may in turn affect HDL structure and function.

PMID- 15487704
TI  - Different effects of platinum, palladium, and rhodium salts on lymphocyte
      proliferation and cytokine release.
AB  - The effects of graded concentrations of Pt, Pd, and Rh salts on spontaneous and
      PHA-stimulated peripheral blood mononuclear cell (PBMC) proliferation and IFN
      gamma, TNF-alpha, and IL-5 release were the focus of this study. Spontaneous PBMC
      proliferation was inhibited by all 10(-4) M salts (with the exception of PtCl2),
      while it was enhanced by 10(-5) M PtCl2 as well as by 10(-5) and 10(-6) M
      (NH4)2[RhCl6] and RhCl3 (but not by 10(-7) M salts). Pt, Pd, and Rh compounds
      showed similar effects on PHA-stimulated PBMC proliferation and cytokine release;
      however, the effects on IFN-gamma release were stronger. Thus, 10(-4) and 10(-5)
      M (NH4)2[PtCl6] and 10(-4) M (NH4)2[PtCl4] inhibited the PHA-stimulated immune
      activity; 10(-4) M PtCl2 did not exert activity, while 10(-6) M (NH4)2[PtCl6] and
      10(-5) and 10(-6) M (NH4)2[PtCl4] and PtCl2 enhanced PBMC proliferation and/or
      cytokine release. (NH4)2[PdCl6] showed stronger dose-related inhibitory effects
      (present also at 10(-7) M concentration) on PHA-stimulated proliferation and
      cytokine release than (NH4)2[PdCl4], PdCl2, or Rh salts; the inhibitory activity
      of (NH4)2[RhCl6] was slightly higher than that of RhCl3. In conclusion, this
      study shows that: (a) the immune capacity of Pt, Pd, and Rh depends on
      speciation; (b) low concentrations of Pt salts stimulate spontaneous and PHA
      stimulated immune responses; (c) the in vitro activity of Pd compounds (which are
      only inhibitory) is higher than that of Pt and Rh salts. These findings are
      consistent with the observations that sensitization and allergic contact
      dermatitis in response to Pd are increased in the general population, although
      the roles of cross-sensitization to Pd and Ni are difficult to determine.

PMID- 15487705
TI  - Use of an automated hematology analyzer and flow cytometry to assess bone marrow
      cellularity and differential cell count.
AB  - The automated analysis of bone marrow aspirates was performed to estimate the
      bone marrow cellularity and differential cell count. Total nucleated cell count
      (TNC) was measured using an automated hematology analyzer. TNC of the bone marrow
      correlated well with the bone marrow cellularity estimated by microscopic
      examination (r = 0.590, p <0.001). The bone marrow cellularity was readily
      confirmed as <30%, from 30 to 70%, or >70% according to TNC. Differential count
      of bone marrow cells was done with the combination of CD45 monoclonal antibody
      and propidium iodide using flow cytometry. Excellent correlations were obtained
      for the population distributions of normoblasts, eosinophils, lymphocytes, and
      blasts between the results of flow cytometry and manual differential counts. The
      percentage of mature granulocytes in flow cytometry showed good correlation with
      the manual percentage of metamyelocytes + neutrophils. The percentage of immature
      granulocytes by flow cytometry showed good correlation with the manual percentage
      of blasts + promyelocytes + myelocytes. These results demonstrate that analysis
      of bone marrow aspirates using an automated hematology analyzer is valuable in
      the determination of bone marrow cellularity. Moreover, as flow cytometry
      provides objective findings for percentages of major cell populations, it can
      serve as a method to automate bone marrow differentials.

PMID- 15487706
TI  - Two prevalent h alleles in para-Bombay haplotypes among 250,000 Taiwanese.
AB  - Alpha(1,2)-fucosyltransferase catalyzes the transfer of fucose to the C-2
      position of galactose on type II precursor substrate Gal beta1-4GlcNAc beta1-R.
      It plays an important biological role in the formation of H antigen, a precursor
      oligosaccharide for both A and B antigens on red blood cells. Aberration of
      alpha(1,2)-fucosyltransferase activity by gene mutations results in decreased
      synthesis of H antigen, leading to the para-Bombay phenotype. In this study, we
      collected about 250,000 blood samples in Taiwan during 5 yr and identified the
      subjects with para-Bombay phenotype. Then we analyzed the sequence of the
      alpha(1,2)-fucosyltransferase gene by direct sequencing and gene cloning methods,
      using the blood samples of 30 para-Bombay individuals and 30 control subjects who
      were randomly selected. The goals of this study were to search for new h alleles,
      to determine the h allele frequencies, and to test whether the sporadic theory is
      applicable in Taiwan. Six different h alleles (ha, 547-548 AG-del; hb, 880-881 TT
      del; hc, R220C; hd, R220H; he, F174L; and hf, N327T) were observed. Two h
      alleles, he and hf, were newly discovered in Taiwan. The he allele has a
      nucleotide 522C>A point mutation, predicting the amino acid 174 substitution of
      Phe to Leu; the hf allele has missense mutation of nucleotide 980A>C, predicting
      the amino acid 327 substitution of Asn to Thr. Frequencies of the 6 alleles are
      ha 46.67%, hb 38.33%, hc 5.00%, hd 1.67%, he 3.33%, and hf 5.00%, respectively.
      These findings in the Taiwanese population confirm previous observations in other
      populations that the Bombay and para-Bombay phenotypes are due to diverse,
      sporadic, nonfunctional alleles, predominantly ha and hb, leading to H deficiency
      of red blood cells. In contrast to previous reports of non-prevalent associations
      of h alleles with para-Bombay phenotype, our results suggest a regional allele
      preference associated with para-Bombay individuals in Taiwan.

PMID- 15487707
TI  - Human chromosome 21-specific DNA markers are useful in prenatal detection of Down
      syndrome.
AB  - Trisomy 21 is the most common chromosomal aberration in live births. In this
      study we employed human chromosome 21-specific short tandem repeat (STR) DNA
      markers to determine the numbers of chromosome 21 present in fetal cells. Forty
      amniotic fluid samples from pregnancies complicated with fetal Down syndrome and
      98 samples from euploid pregnancies were analyzed for D21S11 and interferon-alpha
      receptor (IFNAR) gene intervening sequence. Fluorescent dye-labeled primers were
      used in PCR amplification of these 2 markers. The PCR amplicon was analyzed with
      an automatic DNA sequence analyzer. The results showed that 35 of 40 fetal Down
      syndrome samples analyzed for IFNAR showed 3 distinct peaks, while 24 of 30 cases
      analyzed for D21S11 showed 3 distinct peaks. Two Down syndrome samples showed two
      uneven peaks. By analyzing 98 euploid pregnancies as controls, the ratios of area
      under the peaks were determined to be 1.31 +/- 0.22 and 1.96 +/- 0.18 (mean +/-
      SD) for the euploid pregnancies and pregnancies complicated by fetal Down
      syndrome with 2 peaks, respectively. Our data showed that altogether 39 of 40
      (97.5%) Down syndrome cases were correctly identified based on either the 3-peak
      pattern in one or more of the DNA markers or the relative peak area ratio
      calculation. In conclusion, polymorphic STR DNA markers are useful for
      determining the numbers of chromosome 21 in fetal cells. The high sensitivity and
      automation of the procedures suggest a good prospect for use of this method in
      prenatal detection of fetal Down syndrome. However, this is a preliminary
      investigation and a large-scale study is necessary to validate the clinical
      application of this protocol.

PMID- 15487708
TI  - Association of serum insulin-like growth factor-I and erythropoiesis in relation
      to body iron status.
AB  - This study investigated the associations between serum insulin-like growth factor
      I (IGF-I) concentrations and erythropoietic activities in relation to body iron
      status. Serum IGF-I concentrations, free erythrocyte protoporphyrin (FEP),
      hemograms, and serum iron markers were measured in 71 female adolescents, age 14
      to 17 yr. No significant differences were observed in hemograms, iron parameters,
      or FEP between the subjects with IGF-I <681.2 ng/ml and IGF-I 681.2 ng/ml.
      However, blood hemoglobin and serum iron concentrations averaged 13.4 +/- 0.8
      g/dl and 93.7 +/- 41.2 microg/dl in the subjects with IGF-I >809 ng/ml, which
      were above the values in those with IGF-I <523 ng/ml (12.3 +/- 0.9 g/dl and 50.5
      +/- 30.8 microg/dl, p < 0.05, respectively). On the other hand, FEP was
      significantly lower in the adolescents with IGF-I >809 ng/ml than in those with
      IGF-I <523 ng/ml (38.9 +/- 16.2 microg/dl vs 63.4 +/- 23.1 microg/dl, p <0.05).
      Prevalences of iron deficiency or iron deficiency anemia were 3- or 5-fold higher
      in the subjects with IGF-I <523 ng/ml, compared to those with IGF-I >809 ng/ml.
      Serum IGF-I correlated significantly with FEP (r = -0.45, p <0.05) and serum iron
      concentrations (r = 0.40, p <0.05) in iron deficient subjects. In summary, IGF-I
      seems to have an important relationship to iron metabolism and protoporphyrin
      synthesis in adolescents.

PMID- 15487709
TI  - Effects of different hyaluronic acid products on synovial fluid levels of
      intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in knee
      osteoarthritis.
AB  - The aim of this study was to evaluate the effects of different hyaluronic acid
      (HA) forms on synovial fluid levels of intercellular adhesion molecule-1 (ICAM-1)
      and vascular cell adhesion molecule-1 (VCAM-1) during the treatment of patients
      with knee osteoarthritis (OA). Forty patients were randomly assigned to 2 groups
      that were treated with native sodium hyaluronate (group I) or cross-linked hylan
      G-F 20 (group II). Clinical evaluations and synovial fluid aspirations were
      performed before the 1st injection (baseline), the 2nd injection (week 1), the
      3rd injection (week 2), and at 1 week after the 3rd injection (week 3). Synovial
      fluid levels of both ICAM-1 and VCAM-1 were significantly reduced at weeks 1 to
      3, compared to the baseline values. The Western Ontario and McMaster Universities
      Osteoarthritis (WOMAC) Index was used for clinical evaluations; the WOMAC pain
      score and physical function score were progressively improved at weeks 1 to 3 in
      both groups; the WOMAC stiffness score was significantly improved at week 3 in
      both groups. No significant differences were noted between the 2 treatment groups
      in respect to ICAM-1 levels, VCAM-1 levels, WOMAC pain score, stiffness score, or
      physical function score at any time. The decreased ICAM-1 and VCAM-1 levels after
      intra-articular HA injection may help to explain the anti-inflammatory effects of
      HA therapy in knee OA.

PMID- 15487710
TI  - Automated spectrophotometric assay for urine p-aminophenol by an oxidative
      coupling reaction.
AB  - Urine p-aminophenol (PAP) concentration serves as a biological marker for
      occupational exposures to aniline. We report the development of a rapid, simple
      spectrophotometric method for quantification of urine PAP concentration using a
      chemical autoanalyzer (Olympus Reply). The method involves oxidative coupling of
      PAP with an aromatic compound, xylenol, that contains an electron-donating group,
      based on an electrophilic aromatic substitution reaction catalyzed by sodium
      periodate. A calibration curve is constructed in the same matrix, urine, as the
      unknown samples to be analyzed. In this way, potential matrix interferences are
      largely avoided. The linearity range of the method is 20 to 400 mg/L. Time-course
      studies show that the color formation by reaction of PAP with xylenol is rapid
      and essentially complete within 5 min. Within-run and day-to-day reproducibility
      data at medium (50 mg/L) and high (200 mg/L) concentrations yield CV's <5.0%.
      Several prescription drugs and drugs of abuse, as well as related compounds, gave
      negative tests for interference in the procedure. Clinical applications of the
      method are illustrated by data for (a) PAP concentrations in 255 urine samples
      from workers at a rubber plant, and (b) PAP elimination in serial urine samples
      from 5 volunteers after an oral dose (500 mg) of acetaminophen. In summary, the
      new method has the advantages of automation, operational simplicity, and
      suitability for monitoring workers for exposures to aniline.

PMID- 15487711
TI  - Protective effect of melatonin on experimental otitis media with effusion in
      guinea pigs.
AB  - The aims of this study were: (a) to assess whether the increased oxidative stress
      in otitis media with effusion (OME) induced in guinea pigs by histamine injection
      into the middle ear cavity is reflected by lipid peroxidation in erythrocytes,
      plasma, and middle ear effusion fluid; (b) to survey the alterations of oxidant
      and antioxidant enzyme activities in experimental OME; and (c) to determine the
      effects of melatonin and methylprednisolone on this oxidative stress.
      Malondialdehyde (MDA) level, erythrocyte total (enzymatic plus non-enzymatic)
      superoxide scavenger activity (TSSA), non-enzymatic superoxide scavenger activity
      (NSSA), superoxide dismutase (SOD), catalase (CAT), and xanthine oxidase (XO)
      activities were measured in 4 groups of 7 guinea pigs at 3 hr after injection of
      0.1 ml of histamine (or saline) into the middle ear. Group I was the control
      group, Group II was an experimental group with OME induced by histamine, Group
      III was a melatonin-pretreated OME group, and Group IV was a methylprednisolone
      pretreated OME group. In erythrocyte, plasma, and middle ear effusion samples,
      MDA levels were significantly increased in guinea pigs with OME (Group II),
      compared to controls (Group I); erythrocyte TSSA and SOD activities were lower
      and erythrocyte XO activity was increased in guinea pigs with OME (Group II)
      compared to controls (Group I). No significant differences were found in
      erythrocyte NSSA and CAT activities. In Group III, pretreatment of guinea pigs
      with i.p. melatonin at 1 hr prior to histamine induction of OME decreased the
      erythrocyte, plasma, and effusion MDA levels, compared to Group II; erythrocyte
      XO activity was diminished and erythrocyte TSSA, SOD, and CAT activities were
      increased in Group III compared to Group II. In Group IV, pretreatment of guinea
      pigs with i.p. methylprednisolone at 1 hr prior to histamine induction of OME
      decreased the plasma and effusion MDA levels and increased the erythrocyte TSSA
      and SOD activities, compared to Group II. These results suggest that reactive
      oxygen species (ROS) play a role in histamine-induced OME. Pretreatment with i.p.
      melatonin or methylprednisolone both decrease the ROS generated by experimental
      OME, but melatonin appears to be more effective than methylprednisolone.

PMID- 15487712
TI  - Apolipoprotein E polymorphism in northwestern Greece: frequency and effect on
      lipid parameters.
AB  - Apolipoprotein (apo) E gene polymorphism and its effect on serum lipid parameters
      were examined in a Greek population originating from northwestern Greece (n =
      555). The allele frequencies were epsilon2: 6.3%, epsilon3: 80.7%, and epsilon4:
      13.0%. The epsilon4 allele frequency was higher in our population than was
      previously reported in individuals from other parts of Greece. ApoE polymorphism
      was associated with significant differences in serum lipid, and lipoprotein
      levels. Particularly, individuals with the epsilon2 allele had higher serum
      triglyceride and apoE levels and lower levels of total cholesterol, low-density
      lipoprotein cholesterol, and apoB, compared to those with the alleles epsilon3
      and epsilon4. However, the impact of the epsilon4 allele on lipid parameters seen
      in other populations was not observed in our population. Furthermore, the
      combination of apoE polymorphism and serum apoE concentration explained a larger
      percentage of serum lipid variability than the polymorphism alone. In conclusion,
      the results of our study suggest that ethnic differences, as well as alterations
      of serum apoE levels, significantly modify the relationship between apoE gene
      polymorphism and serum lipid variability.

PMID- 15487713
TI  - A note from history: the first tumor pathologist.

PMID- 15487714
TI  - The growth of biomedical engineering is a major challenge to medical physics. For
      the proposition.

PMID- 15487715
TI  - The growth of biomedical engineering is a major challenge to medical physics.
      Against the proposition.

PMID- 15487716
TI  - A new theory of phase-contrast x-ray imaging based on Wigner distributions.
AB  - There is a pressing need for a comprehensive theory for phase-contrast x-ray
      imaging to guide its development and clinical applications. This work presents
      such a theory as the foundation for deriving these guidelines. The new theory is
      based on the Wigner-distributions for the parabolic wave equations, and it is
      more general than the present theories based on the Fresnel-Kirchhoff diffraction
      theory. The new theory shows for the first time how the complex degree of
      coherence (CDC) of the incident x-ray beam determines the phase-contrast
      visibility in general, and how the reduced complex degree of coherence (RCDC) for
      an anode-source is equal to the system's optical transfer function for geometric
      unsharpness in particular. The role of detector resolution in phase visibility
      has been clarified as well. Computer simulations based on the new theory were
      conducted and optimal design parameters were derived for phase-contrast
      mammography systems.

PMID- 15487717
TI  - A novel reconstruction algorithm to extend the CT scan field-of-view.
AB  - For various reasons, a projection dataset acquired on a computed tomography (CT)
      scanner can be truncated. That is, a portion of the scanned object is positioned
      outside the scan field-of-view (SFOV) and the line integrals corresponding to
      those regions are not measured. A projection truncation problem causes imaging
      artifacts that lead to suboptimal image quality. In this paper, we propose a
      reconstruction algorithm that enables an adequate estimation of the projection
      outside the SFOV. We make use of the fact that the total attenuation of each
      ideal projection in a parallel sampling geometry remains constant over views. We
      use the magnitudes and slopes of the projection samples at the location of
      truncation to estimate water cylinders that can best fit to the projection data
      outside the SFOV. To improve the robustness of the algorithm, continuity
      constraints are placed on the fitting parameters. Extensive phantom and patient
      experiments were conducted to test the robustness and accuracy of the proposed
      algorithm.

PMID- 15487718
TI  - Dosimetric properties of improved GafChromic films for seven different
      digitizers.
AB  - Two recently introduced GafChromic film models, HS and XR-T, have been developed
      as more sensitive and uniform alternatives to GafChromic MD-55-2 film. The HS
      model has been specifically designed for measurement of absorbed dose in high
      energy photon beams (above 1 MeV), while the XR-T model has been introduced for
      dose measurements of low energy (0.1 MeV) photons. The goal of this study is to
      compare the sensitometric curves and estimated dosimetric uncertainties
      associated with seven different GafChromic film dosimetry systems for the two new
      film models. The densitometers tested are: LKB Pharmacia UltroScan XL, Molecular
      Dynamics Personal Densitometer, Nuclear Associates Radiochromic Densitometer
      Model 37-443, Photoelectron Corporation CMR-604, Laser Pro 16, Vidar VXR-16, and
      AGFA Arcus II document scanner. Pieces of film were exposed to different doses in
      a dose range from 0.5 to 50 Gy using 6 MV photon beam. Functional forms for dose
      vs net optical density have been determined for each of the GafChromic film
      dosimetry systems used in this comparison. Two sources of uncertainties in dose
      measurements, governed by the experimental measurement and calibration curve fit
      procedure, have been compared for the densitometers used. Among the densitometers
      tested, it is found that for the HS film type the uncertainty caused by the
      experimental measurement varies from 1% to 3% while the calibration fit
      uncertainty ranges from 2% to 4% for doses above 5 Gy. Corresponding
      uncertainties for XR-T film model are somewhat higher and range from 1% to 5% for
      experimental and from 2% to 7% for the fit uncertainty estimates. Notwithstanding
      the significant variations in sensitivity, the studied densitometers exhibit very
      similar precision for GafChromic film based dose measurements above 5 Gy.

PMID- 15487719
TI  - Effects of the intensity levels and beam map resolutions on static IMRT plans.
AB  - In this study we focus on how the intensity level and multileaf collimator (MLC)
      resolution affect the quality of IMRT plans using the static MLC delivery
      technique. The planning process is based on a least-square dose-based quadratic
      function and uses a simulated annealing algorithm to sample the discrete
      variables. Three clinical cases are studied empirically: a medulloblastoma, a
      prostate, and an oropharyngeal carcinoma. The intensity levels used are 3, 5, 10,
      20, and continuous; the map resolution varies from 0.15-1.5 cm, with the leaf
      width equal to the step size. The influence of these two parameters are studied
      by comparing the cost value and the cost of delivery time from a trade-off point
      of view. An "efficient frontier" is drawn by connecting the plans with the lowest
      cost value at any given resolutions. For each case, a practical delivery region
      is defined by doubling the delivery time needed at a normal setting (five levels,
      1.0 cm). Within this region, the "efficient frontier" demonstrates that the plans
      with five intensity levels are the most efficient comparing with plans with
      higher levels. This is a confirmation of the conclusion from Keller-Reichenbecher
      et al. [Int. J. Radiat. Oncol., Biol., Phys. 45, 1315-1324 (1999)]. It indicates
      that to further improve the plan quality with the minimal cost of extra delivery
      time, the most economical way is to improve the resolution rather than using
      higher intensity levels.

PMID- 15487720
TI  - Technical note: A novel boundary condition using contact elements for finite
      element based deformable image registration.
AB  - Deformable image registration is an important tool for image-guided radiotherapy.
      Physics-model-based deformable image registration using finite element analysis
      is one of the methods currently being investigated. The calculation accuracy of
      finite element analysis is dependent on given boundary conditions, which are
      usually based on the surface matching of the organ in two images. Such a surface
      matching, however, is hard to obtain from medical images. In this study, we
      developed a new boundary condition to circumvent the traditional difficulties.
      Finite element contact-impact analysis was employed to simulate the interaction
      between the organ of interest and the surrounding body. The displacement loading
      is not necessarily specified. The algorithm automatically deforms the organ model
      into the minimum internal energy state. The analysis was performed on CT images
      of the lung at two different breathing phases (exhalation and full inhalation).
      The result gave the displacement vector map inside the lung. Validation of the
      result showed satisfactory agreement in most parts of the lung. This approach is
      simple, operator independent and may provide improved accuracy of the prediction
      of organ deformation.

PMID- 15487721
TI  - An EGSnrc Monte Carlo study of the microionization chamber for reference
      dosimetry of narrow irregular IMRT beamlets.
AB  - Intensity modulated radiation therapy (IMRT) has evolved toward the use of many
      small radiation fields, or "beamlets," to increase the resolution of the
      intensity map. The size of smaller beamlets can be typically about 1-5 cm2.
      Therefore small ionization chambers (IC) with sensitive volumes < or = 0.1 cm3
      are generally used for dose verification of IMRT treatment. The dosimetry of
      these narrow photon beams pertains to the so-called nonreference conditions for
      beam calibration. The use of ion chambers for such narrow beams remains
      questionable due to the lack of electron equilibrium in most of the field. The
      present contribution aims to estimate, by the Monte Carlo (MC) method, the total
      correction needed to convert the IBA-Wellhofer NAC007 micro IC measured charge in
      such radiation field to the absolute dose to water. Detailed geometrical
      simulation of the microionization chamber was performed. The ion chamber was
      always positioned at a 10 cm depth in water, parallel to the beam axis. The
      delivered doses to air and water cavity were calculated using the CAVRZ EGSnrc
      user code. The 6 MV phase-spaces for Primus Clinac (Siemens) used as an input to
      the CAVRZnrc code were derived by BEAM/EGS4 modeling of the treatment head of the
      machine along with the multileaf collimator [Sanchez-Doblado et al., Phys. Med.
      Biol. 48, 2081-2099 (2003)] and contrasted with experimental measurements. Dose
      calculations were carried out for two irradiation geometries, namely, the
      reference 10x10 cm2 field and an irregular (approximately 2x2 cm2) IMRT beamlet.
      The dose measured by the ion chamber is estimated by MC simulation as a dose
      averaged over the air cavity inside the ion-chamber (Dair). The absorbed dose to
      water is derived as the dose deposited inside the same volume, in the same
      geometrical position, filled and surrounded by water (Dwater) in the absence of
      the ionization chamber. Therefore, the Dwater/Dair dose ratio is a MC direct
      estimation of the total correction factor needed to convert the absorbed dose in
      air to absorbed dose to water. The dose ratio was calculated for several chamber
      positions, starting from the penumbra region around the beamlet along the two
      diagonals crossing the radiation field. For this quantity from 0 up to a 3%
      difference is observed between the dose ratio values obtained within the small
      irregular IMRT beamlet in comparison with the dose ratio derived for the
      reference 10x10 cm2 field. Greater differences from the reference value up to 9%
      were obtained in the penumbra region of the small IMRT beamlet.

PMID- 15487722
TI  - The phantom portion of the American College of Radiology (ACR) computed
      tomography (CT) accreditation program: practical tips, artifact examples, and
      pitfalls to avoid.
AB  - The ACR CT accreditation program, begun in 2002, requires the submission of
      approximately 20 images, several completed data sheets and printouts of three
      Excel worksheets. The procedure manual is very detailed, yet participants
      unfamiliar with the program or having minimal CT experience have needed to redo
      aspects of their submission, or in some cases do not receive accreditation, due
      to mistakes made by the physicist. This review of the phantom portion of the ACR
      CT accreditation program supplements the ACR provided instructions with
      additional photos of phantom setup, region-of-interest (ROI), and image placement
      on the film sheets, and examples of completed portions of actual (but anonymous)
      submissions. Common mistakes, as well as uncommon but interesting images, are
      shown and explanations are given as to what could have been done to avoid the
      problem. Additionally, a review of CT dose measurement techniques and
      calculations will enable the physicist to better assist sites where typical exam
      doses are above the ACR reference values.

PMID- 15487723
TI  - Asymmetric fan beams (AFB) for improvement of the craniocaudal dose distribution
      in helical tomotherapy delivery.
AB  - Helical tomotherapy (HT) is a novel radiotherapy technique that utilizes
      intensity modulated fan beams that deliver highly conformal dose distributions in
      a helical beam trajectory. The most significant limitation in dose delivery with
      a constant fan beam thickness (FBT) is the penumbra width of the dose
      distribution in the craniocaudal direction, which is equivalent to the FBT. We
      propose to employ a half-blocked fan beam at start and stop location to reduce
      the penumbra width by half. By opening the jaw slowly during the helical delivery
      until the desired FBT is achieved it is possible to create a sharper edge in the
      superior and inferior direction from the target. The technique was studied using
      a tomotherapy beam model implemented on a commercial treatment planning system
      (Theraplan Plus V3.0). It was demonstrated that the dose distribution delivered
      using a 25 mm fan beam can be improved significantly, to reduce the dose to
      normal structures located superiorly and inferiorly of the target. Dosimetry for
      this technique is straightforward down to a FBT of 15 mm and implementation
      should be simple as no changes in couch movement are required compared to a
      standard HT delivery. We conclude that the use of asymmetric collimated fan beams
      for the start and stop of the helical tomotherapeutic dose delivery has the
      potential of significantly improving the dose distribution in helical
      tomotherapy.

PMID- 15487724
TI  - Radiation absorbed dose distribution in a patient treated with yttrium-90
      microspheres for hepatocellular carcinoma.
AB  - We have implemented a three-dimensional dose calculation technique accounting for
      dose inhomogeneity within the liver and tumor of a patient treated with 90Y
      microspheres. Single-photon emission computed tomography (SPECT) images were used
      to derive the activity distribution within liver. A Monte Carlo calculation was
      performed to create a voxel dose kernel for the 90Y source. The activity
      distribution was convolved with the voxel dose kernel to obtain the three
      dimensional (3D) radiation absorbed dose distribution. An automated technique was
      developed to accurately register the computed tomography (CT) and SPECT scans in
      order to display the 3D dose distribution on the CT scans. In addition, dose
      volume histograms were generated to fully analyze the tumor and liver doses. The
      calculated dose-volume histogram indicated that although the patient was treated
      to the nominal whole liver dose of 110 Gy, only 16% of the liver and 83% of the
      tumor received a dose higher than 110 Gy. The mean tumor and liver doses were 163
      and 58 Gy, respectively.

PMID- 15487725
TI  - Ionization chamber-based reference dosimetry of intensity modulated radiation
      beams.
AB  - The present paper addresses reference dose measurements using thimble ionization
      chambers for quality assurance in IMRT fields. In these radiation fields,
      detector fluence perturbation effects invalidate the application of open-field
      dosimetry protocol data for the derivation of absorbed dose to water from
      ionization chamber measurements. We define a correction factor C(Q)IMRT to
      correct the absorbed dose to water calibration coefficient N(D, w)Q for fluence
      perturbation effects in individual segments of an IMRT delivery and developed a
      calculation method to evaluate the factor. The method consists of precalculating,
      using accurate Monte Carlo techniques, ionization chamber, type-dependent cavity
      air dose, and in-phantom dose to water at the reference point for zero-width
      pencil beams as a function of position of the pencil beams impinging on the
      phantom surface. These precalculated kernels are convolved with the IMRT fluence
      distribution to arrive at the dose-to-water-dose-to-cavity air ratio [D(a)w
      (IMRT)] for IMRT fields and with a 10x10 cm2 open-field fluence to arrive at the
      same ratio D(a)w (Q) for the 10x10 cm2 reference field. The correction factor
      C(Q)IMRT is then calculated as the ratio of D(a)w (IMRT) and D(a)w (Q). The
      calculation method was experimentally validated and the magnitude of chamber
      correction factors in reference dose measurements in single static and dynamic
      IMRT fields was studied. The results show that, for thimble-type ionization
      chambers the correction factor in a single, realistic dynamic IMRT field can be
      of the order of 10% or more. We therefore propose that for accurate reference
      dosimetry of complete n-beam IMRT deliveries, ionization chamber fluence
      perturbation correction factors must explicitly be taken into account.

PMID- 15487726
TI  - Brachytherapy dosimetry parameters calculated for a new 103Pd source.
AB  - A new brachytherapy source having 103Pd adsorbed onto silver beads has been
      designed. The dose distributions of this source have been characterized using
      version 5 of the MCNP Monte Carlo radiation transport code available from Oak
      Ridge National Laboratory. These results are presented in terms of the updated
      AAPM Task Group No. 43 (TG-43U1) formalism, dosimetry parameters, and recommended
      calculation methodology.

PMID- 15487727
TI  - Patient dose in digital mammography.
AB  - In the present investigation, we analyze the dose of 5034 patients (20,137
      images) who underwent mammographic examinations with a full-field digital
      mammography system. Also, we evaluate the system calibration by analyzing the
      exposure factors as a function of breast thickness. The information relevant to
      this study has been extracted from the image DICOM header and stored in a
      database during a 3-year period (March 2001-October 2003). Patient data included
      age, breast thickness, kVp, mAs, target/filter combination, and nominal dose
      values. Entrance surface air kerma (ESAK) without backscatter was calculated from
      the tube output as measured for each voltage used under clinical conditions and
      from the tube loading (mAs) included in the DICOM header. Mean values for the
      patient age and compressed breast thickness were 56 years (SD: 11) and 52 mm (SD:
      13), respectively. The majority of the images was acquired using the STD (for
      standard) automatic mode (98%). The most frequent target/filter combination
      automatically selected for breast smaller than 35 mm was Mo/Mo (75%); for
      intermediate thicknesses between 35 and 65 mm, the combinations were Mo/Rh (54%)
      and Rh/Rh (38.5%); Rh/Rh was the combination selected for 91% of the cases for
      breasts thicker than 65 mm. A wide kVp range was observed for each target/filter
      combination. The most frequent values were 28 kVp for Mo/Mo, 29 kVp for Mo/Rh,
      and 29 and 30 kV for Rh/Rh. Exposure times ranged from 0.2 to 4.2 s with a mean
      value of 1.1 s. Average glandular doses (AGD) per exposure were calculated by
      multiplying the ESAK values by the conversion factors tabulated by Dance for
      women in the age groups 50 to 64 and 40 to 49. This approach is based on the
      dependence of breast glandularity on breast thickness and age. The total mean
      average glandular dose (AGD(T)) was calculated by summing the values associated
      with the pre-exposure and with the main exposure. Mean AGD(T) per exposure was
      1.88 mGy (CI 0.01) and the mean AGD(T) per examination was 3.8 mGy, with 4 images
      per examination on average. The mean dose for cranio-caudal view (CC) images was
      1.8 mGy, which is lower than that for medio-lateral oblique (MLO) view because
      the thickness for CC images was on average 10% lower than that for MLO images.
      Mean AGD(T) for the oldest group of women (1.90) was 3% higher than the AGD(T)
      for the younger group (1.85) due to the larger compressed breast thickness of
      women in the older group (10% on average). Differences between the corresponding
      AGD(T) values of each age group were lowest for breast thicknesses in the range
      40-60 mm, being slightly higher for the women in the older group.

PMID- 15487728
TI  - Output ratio in air for MLC shaped irregular fields.
AB  - For accurate monitor unit calculation, it is important to calculate the output
      ratio in air, Sc, for an irregular field shaped by MLC. We have developed an
      algorithm to calculate Sc based on an empirical model [Med. Phys. 28, 925-937
      (2001)] by projecting each leaf position to the isocenter plane. Thus it does not
      require the exact knowledge of the head geometry. Comparisons were made for three
      different types of MLC: those with MLC replacing the inner collimator jaws; those
      with MLC replacing the outer collimator jaws; and those with MLC as a tertiary
      attachment. When the MLC leaf positions are substantially different from the
      secondary collimators (or the rectangular field encompassing the irregular
      field), one observes an up to 5% difference in the value of head-scatter
      correction factor, HCF, defined as the ratio of output ratio in air between the
      MLC shaped irregular field and that of the rectangular field encompassing the
      irregular field. No collimator exchange effect was observed for rectangular
      fields shaped by MLC (e.g., 5x30 and 30x5 cm2 diagonal) when the secondary
      collimators are fixed, unlike that for the rectangular fields shaped by the inner
      and outer collimator jaws, where it can be 1-2%. For the same MLC shaped
      irregular field, the value of Sc increases from the Elekta, to the Siemens, to
      the Varian accelerators, with an up to 4% difference. The calculation agrees with
      measurement to within 1.2% for points both on and off the central-axis. The
      fitting parameters used in the algorithm are derived from measurements for square
      field sizes on the central-axis.

PMID- 15487729
TI  - Development of a 30-week-pregnant female tomographic model from computed
      tomography (CT) images for Monte Carlo organ dose calculations.
AB  - Assessment of radiation dose and risk to a pregnant woman and her fetus is an
      important task in radiation protection. Although tomographic models for male and
      female patients of different ages have been developed using medical images, such
      models for pregnant women had not been developed to date. This paper reports the
      construction of a partial-body model of a pregnant woman from a set of computed
      tomography (CT) images. The patient was 30 weeks into pregnancy, and the CT scan
      covered the portion of the body from above liver to below pubic symphysis in 70
      slices. The thickness for each slice is 7 mm, and the image resolution is 512x512
      pixels in a 48 cm x 48 cm field; thus, the voxel size is 6.15 mm3. The images
      were segmented to identify 34 major internal organs and tissues considered
      sensitive to radiation. Even though the masses are noticeably different from
      other models, the three-dimensional visualization verified the segmentation and
      its suitability for Monte Carlo calculations. The model has been implemented into
      a Monte Carlo code, EGS4-VLSI (very large segmented images), for the calculations
      of radiation dose to a pregnant woman. The specific absorbed fraction (SAF)
      results for internal photons were compared with those from a stylized model.
      Small and large differences were found, and the differences can be explained by
      mass differences and by the relative geometry differences between the source and
      the target organs. The research provides the radiation dosimetry community with
      the first voxelized tomographic model of a pregnant woman, opening the door to
      future dosimetry studies.

PMID- 15487730
TI  - Automatic measurements of image geometry for online calibration of C-arm
      fluoroscopy.
AB  - Calibrated C-arm fluoroscopy is used for a variety of surgical procedures where
      surgical tools and anatomical structures need to be located in space. Calibration
      can be performed online by combining measurements of the geometry of the image
      (center and radius) with measurements of a grid of fiducial markers. This article
      focuses on the first aspect--image geometry--and describes a method to perform
      the geometry measurements automatically. The accuracy, robustness, and speed of
      the method are validated on 100 images obtained from several hospitals with
      different C-arm scanners. All 100 images were successfully measured with an
      average error of 0.8 mm for the center and 0.8 mm for the radius. The execution
      time is less than one second per image.

PMID- 15487731
TI  - Dose response characteristics of new models of GAFCHROMIC films: dependence on
      densitometer light source and radiation energy.
AB  - This paper presents a systematic study of the dose response characteristics of
      two new models and one commonly used model of GAFCHROMIC film: HS, XR-T, and MD55
      2, respectively. We irradiated these film models with three different radiation
      sources: I-125, Ir-192, and 6 MV photon beam (6 MVX). We scanned the films with
      three different densitometers: a He-Ne laser with a wavelength of 633 nm, a spot
      densitometer with a wavelength of 671 nm, and a CCD camera densitometer with
      interchangeable LED boxes with wavelengths of 665 nm (red), 520 nm (green), and
      465 nm (blue). We compared the film sensitivities in terms of net optical density
      (NOD) per unit dose in Gy. The sensitivity of each film model depends on
      radiation energy and the densitometer light source. Using He-Ne laser based
      densitometer as a reference standard, we found the sensitivities (NOD/Gy) for the
      red lights of wavelengths, 671 nm and 665 nm, are higher by factors of about 2.5
      and 2, respectively. The sensitivities for green (520 nm) and blue (465 nm)
      lights are lower than that for He-Ne laser (633 nm) by factors of about 2 and 4,
      respectively. The energy dependence of the sensitivity varies with the film
      model, but is similar for all densitometer light sources. Comparing I-125 to Ir
      192 and 6MVX, we note that (a) model XR-T is about eight times more sensitive,
      and (b) models HS and MD55-2 are about 40% less sensitive. Relative to MD55-2, XR
      T is 12 times more sensitive for I-125 but comparable for Ir-192 and 6MVX,
      whereas HS is 2 to 3 times more sensitive in all cases. This set of results can
      serve as useful information for making decisions in selecting the film model and
      compatible densitometer to achieve the best accuracy of dosimetry in the
      appropriate dose range.

PMID- 15487732
TI  - Evaluation of the goodness of fit of solar simulated radiation to a reference
      solar spectrum for photobiological experiments.
AB  - There is a great need for photochemical and photobiological experiments to mimic
      the spectral distribution of solar ultraviolet radiation by artificial
      ultraviolet sources. The spectral distribution of various ultraviolet sources
      were compared with a reference solar spectrum which represents a realistic
      maximum solar spectrum under cloudless sky. Various methods to compare the
      artificial sources with the COLIPA solar reference spectrum were presented.
      Beside a graphical method which is based on the Lorenz curve also integral
      indices were used to characterize the deviations from the solar spectrum.
      Following parameters should be used to characterize an artificial source: (1)
      total output of the biologically effective irradiance, (2) maximum deviation of
      the cumulative relative spectral irradiance of the biologically effective solar
      simulated radiation, (3) spectral distribution of the difference of the
      cumulative relative spectral irradiance of the biologically effective solar
      simulated radiation, and (4) the index of the goodness of the spectral fit.
      Further on upper and lower limit values are suggested to improve the quality of
      the spectral fit of solar simulated radiation and the irradiance maximum should
      be limited to the range in which dose reciprocity is known to be conserved.

PMID- 15487733
TI  - Metallic copper as a fiducial marker for both CT and PET.
AB  - There is great interest in augmenting computed tomography (CT) with information
      gained from other imaging modalities. Positron emission tomography (PET) provides
      valuable data related to patient physiology to aid in the delineation of tumor
      volumes. Combining the information provided by these imaging modalities requires
      accurate spatial registration of the two data sets. Fiducial based mapping
      provides straightforward registration based on corresponding landmark points or
      fiducials in the two image sets. When external fiducials are employed, consistent
      intermodality marker placement and centroid identification are essential to
      achieving an accurate and reliable registration. Similarity of marker design
      between modalities greatly aides in achieving this goal. Solid copper may serve
      as a fiducial marker in both CT and PET. Small spheres or wires of copper are
      readily visible in CT while neutron activation of these same markers produces
      positron emitting Copper-64 for detection by PET. The use of identical shaped
      markers in both imaging modalities greatly simplifies the task of intermodality
      centroid matching. Copper has excellent machining properties and, prior to
      activation, is easy and safe to handle. The feasibility of Cu as a marker for
      both CT and PET is demonstrated using imaging phantoms.

PMID- 15487734
TI  - An investigation of accelerator head scatter and output factor in air.
AB  - Our purpose in this study was to investigate whether the Monte Carlo simulation
      can accurately predict output factors in air. Secondary goals were to study the
      head scatter components and investigate the collimator exchange effect. The Monte
      Carlo code, BEAMnrc, was used in the study. Photon beams of 6 and 18 MV were from
      a Varian Clinac 2100EX accelerator and the measurements were performed using an
      ionization chamber in a mini-phantom. The Monte Carlo calculated in air output
      factors was within 1% of measured values. The simulation provided information of
      the origin and the magnitude of the collimator exchange effect. It was shown that
      the collimator backscatter to the beam monitor chamber played a significant role
      in the beam output factors. However the magnitude of the scattered dose
      contributions from the collimator at the isocenter is negligible. The maximum
      scattered dose contribution from the collimators was about 0.15% and 0.4% of the
      total dose at the isocenter for a 6 and 18 MV beam, respectively. The scattered
      dose contributions from the flattening filter at the isocenter were about 0.9-3%
      and 0.2-6% of the total dose for field sizes of 4x4 cm2-40x40 cm2 for the 6 and
      18 MV beam, respectively. The study suggests that measurements of head scatter
      factors be done at large depth well beyond the depth of electron contamination.
      The insight information may have some implications for developing generalized
      empirical models to calculate the head scatter.

PMID- 15487735
TI  - Comparison study of MOSFET detectors and diodes for entrance in vivo dosimetry in
      18 MV x-ray beams.
AB  - The feasibility of dual bias dual metal oxide semiconductor field effect
      transistors (MOSFETs) for entrance in vivo dose measurements in high energy x
      rays beams (18 MV) was investigated. A comparison with commercially available
      diodes for in vivo dosimetry for the same energy range was performed. As MOSFETs
      are sold without an integrated build-up cap, different caps were tested: 3 cm
      bolus, 2 cm bolus, 2 cm hemispherical cap of a water equivalent material (Plastic
      Water) and a metallic hemispherical cap. This metallic build-up cap is the same
      as the one that is mounted on the in vivo diode used in this study. Intrinsic
      precision and response linearity with dose were determined for MOSFETs and
      diodes. They were then calibrated for entrance in vivo dosimetry in an 18 MV x
      ray beam. Calibration included determination of the calibration factor in
      standard reference conditions and of the correction factors (CF) when irradiation
      conditions differed from those of reference. Correction factors for field size,
      source surface distance, wedge, and temperature were determined. Sensitivity
      variation with accumulated dose and the lifetime of both types of detectors were
      also studied. Finally, the uncertainties of entrance in vivo measurements using
      MOSFET and diodes were discussed. Intrinsic precision for MOSFETs for the high
      sensitivity mode was 0.7% (1 s.d.) as compared to the 0.05% (1 s.d.) for the
      studied diodes. The linearity of the response with dose was excellent (R2 =
      1.000) for both in vivo dosimetry systems. The absolute values of the studied
      correction factors for the MOSFETs when covered by the different build-up caps
      were of the same order of those determined for the diodes. However, the
      uncertainties of the correction factors for MOSFETs were significantly higher
      than for diodes. Although the intrinsic precision and the uncertainty on the CF
      was higher for MOSFET detectors than for the studied diodes, the total
      uncertainty in entrance dose determination, once they were calibrated, was of
      2.9% (1 s.d.) while for diodes it was 2.0% (1 s.d.). MOSFETs showed no
      sensitivity variation with accumulated dose or temperature. When used in the high
      sensitivity mode, after approximately 50 Gy of accumulated dose MOSFETs could no
      longer be used as radiation dosimeters. In conclusion, MOSFETs can be used for
      entrance in vivo dosimetry in high energy x-rays beams if covered by an
      appropriate build-up cap. Metallic build-up caps, such as those used for in vivo
      diodes, have the advantage of greater patient comfort and less perturbation of
      the treatment field than the other build-up caps tested, while keeping the
      correction factors of the same order.

PMID- 15487736
TI  - Dose uncertainty due to computed tomography (CT) slice thickness in CT-based high
      dose rate brachytherapy of the prostate cancer.
AB  - In computed tomography (CT)-based high dose rate (HDR) brachytherapy, the
      uncertainty in the localization of the longitudinal catheter-tip positions due to
      the discrete CT slice thickness, results in a delivered dose uncertainty.
      Catheter coordinates were extracted from five patients treated for prostate
      cancer, and three simulation scenarios were followed to mimic the longitudinal
      imprecision of the catheter tips, hence the dwell positions. All catheters were
      displaced (1) forward, (2) backward, or (3) randomly distributed within the space
      defined by one CT slice thickness, for thicknesses ranging from 2 to 5 mm.
      Average and standard deviation values of the relative dose variations are
      reported for the various catheter displacement scenarios. Also, the dose points
      were grouped according to their relative position in the prostate, inner,
      peripheral and outer area of prostate and base, median and apex zones, in order
      to estimate the spatial sensitivity of the dose errors. For scenarios (1) and
      (2), the dose uncertainties due to the finite slice thickness increase linearly
      with the slice spacing, from 3% to 8% for the slice thickness values ranging from
      2 to 5 mm, respectively. The more realistic scenario (3) yields average errors
      ranging from 0.7% to 1.7%. The apex and the base show larger dose errors and
      variability of dose errors than the median of the prostate. No statistical
      difference was observed among different transversal sections of the prostate. A
      CT slice thickness of 3 mm appears to be a good compromise showing an acceptable
      average dose uncertainty of 1%, without unduly increasing the number of slices.

PMID- 15487737
TI  - Characteristics relevant to portal dosimetry of a cooled CCD camera-based EPID.
AB  - Our EPIDs have recently been equipped with Peltier-cooled CCD cameras. The CCD
      cooling dramatically reduced deteriorating effects of radiation damage on image
      quality. Over more than 600 days of clinical operation, the radiation induced
      noise contribution has remained stable at a very low level (1 SD < or = 0.15% of
      the camera dynamic range), in marked contrast with the previously used noncooled
      cameras. The camera response (output signal versus incident EPID radiation
      exposure) can be accurately described with a quadratic function. This response
      reproduced well, both in short and long term (variation < 0.2% respectively <
      0.4% (1 SD)), rendering the cooled camera well-suited for EPID dosimetry
      applications.

PMID- 15487738
TI  - An ROC comparison of four methods of combining information from multiple images
      of the same patient.
AB  - Variance of diagnostic information contained in an image degrades diagnostic
      accuracy. Acquiring multiple images of the same patient (e.g., mediolateral
      oblique and craniocaudal view mammograms) can, in principle, help reduce this
      degradation. We demonstrate how this can be accomplished in the context of
      computer-aided diagnosis (CAD). Assuming that computer outputs obtained from
      multiple images of the same patient can be transformed monotonically to the same
      pair of truth-conditional normal distributions and, for simplicity, ignoring
      correlation among images, we investigate theoretically four methods of combining
      the computer outputs: taking the average, the median, the maximum, or the
      minimum. We found, as one would expect, that both the average and the median
      always produce an improved area under the receiver operating characteristic (ROC)
      curve (AUC) compared to the single-view images, while the average always produces
      better performance than the median. However, the maximum and minimum also can
      produce improved AUCs in some situations, and under certain conditions can
      outperform the average. Surprisingly, we found that the maximum and minimum of
      normally-distributed decision variables produce nearly binormal ROC curves. These
      results can be used as a guide in attempting to increase the efficacy of CAD when
      multiple images are available from the same patient.

PMID- 15487739
TI  - How should low-contrast detail detectability be measured in fluoroscopy?
AB  - The relationship and precision of four methods for measuring the low-contrast
      detail detectability in fluoroscopic imaging were studied. These included the
      physical measurement of the accumulation rate of the square of the signal-to
      noise ratio (SNR(rate)2), two-alternative forced-choice (2-AFC) experiments,
      sixteen-alternative forced-choice (16-AFC) experiments and subjective
      determination of the threshold contrast. The precision and sensitivity of the
      threshold contrast measurement were seen to be modest in the constancy testing of
      fluoroscopic equipment: only large changes in system performance could be
      reliably detected by that method. The measurement of the SNR(rate)2 is suggested
      instead. The relationship between the results of the various methods were
      studied, and it was found that human performance can be related to SNR(rate)2 by
      introducing the concept of the effective image information integration time
      (t(eff)). When measured for an unlimited observation time, it depicts the
      saturation of human performance in detecting a static low-contrast detail in
      dynamic image noise. Here, t(eff) was found to be about 0.6 s in 2-AFC tests and
      0.3 s in 16-AFC tests.

PMID- 15487740
TI  - Using FDG-PET activity as a surrogate for tumor cell density and its effect on
      equivalent uniform dose calculation.
AB  - The concept of equivalent uniform dose (EUD) has been suggested as a means to
      quantitatively consider heterogeneous dose distributions within targets. Tumor
      cell density/function is typically assumed to be uniform. We herein propose to
      use 18F-labeled 2-deoxyglucose (FDG) positron emission tomography (PET) tumor
      imaging activity as a surrogate marker for tumor cell density to allow the EUD
      concept to include intratumor heterogeneities and to study its effect on EUD
      calculation. Thirty-one patients with lung cancer who had computerized tomography
      (CT)-based 3D planning and PET imaging were studied. Treatment beams were
      designed based on the information from both the CT and PET scans. Doses were
      calculated in 3D based on CT images to reflect tissue heterogeneity. The EUD was
      calculated in two different ways: first, assuming a uniform tumor cell density
      within the tumor target; second, using FDG-PET activity (counts/cm3) as a
      surrogate for tumor cell density at different parts of tumor to calculate the
      functional-imaging-weighted EUD (therefore will be labeled fEUD for convenience).
      The EUD calculation can be easily incorporated into the treatment planning
      process. For 28/31 patients, their fEUD and EUD differed by less than 6%. Twenty
      one of these twenty-eight patients had tumor volumes < 200 cm3. In the three
      patients with larger tumor volume, the fEUD and EUD differed by 8%-14%.
      Incorporating information from PET imaging to represent tumor cell density in the
      EUD calculation is straightforward. This approach provides the opportunity to
      include heterogeneity in tumor function/metabolism into the EUD calculation. The
      difference between fEUD and EUD, i.e., whether including or not including the
      possible tumor cell density heterogeneity within tumor can be significant with
      large tumor volumes. Further research is needed to assess the usefulness of the
      fEUD concept in radiation treatment.

PMID- 15487742
TI  - X-ray imaging performance of structured cesium iodide scintillators.
AB  - Columnar structured cesium iodide (CsI) scintillators doped with Thallium (Tl)
      have been used extensively for indirect x-ray imaging detectors. The purpose of
      this paper is to develop a methodology for systematic investigation of the
      inherent imaging performance of CsI as a function of thickness and design type.
      The results will facilitate the optimization of CsI layer design for different x
      ray imaging applications, and allow validation of physical models developed for
      the light channeling process in columnar CsI layers. CsI samples of different
      types and thicknesses were obtained from the same manufacturer. They were
      optimized either for light output (HL) or image resolution (HR), and the
      thickness ranged between 150 and 600 microns. During experimental measurements,
      the CsI samples were placed in direct contact with a high resolution CMOS optical
      sensor with a pixel pitch of 48 microns. The modulation transfer function (MTF),
      noise power spectrum (NPS), and detective quantum efficiency (DQE) of the
      detector with different CsI configurations were measured experimentally. The
      aperture function of the CMOS sensor was determined separately in order to
      estimate the MTF of CsI alone. We also measured the pulse height distribution of
      the light output from both the HL and HR CsI at different x-ray energies, from
      which the x-ray quantum efficiency, Swank factor and x-ray conversion gain were
      determined. Our results showed that the MTF at 5 cycles/mm for the HR type was
      50% higher than for the HL. However, the HR layer produces approximately 36% less
      light output. The Swank factor below K-edge was 0.91 and 0.93 for the HR and HL
      types, respectively, thus their DQE(0) were essentially identical. The
      presampling MTF decreased as a function of thickness L. The universal MTF, i.e.,
      MTF plotted as a function of the product of spatial frequency f and CsI thickness
      L, increased as a function of L. This indicates that the light channeling process
      in CsI improved the MTF of thicker layers more significantly than for the thinner
      ones.

PMID- 15487741
TI  - Automatic detection and classification of hypodense hepatic lesions on contrast
      enhanced venous-phase CT.
AB  - The objective of this work was to develop and validate algorithms for detection
      and classification of hypodense hepatic lesions, specifically cysts, hemangiomas,
      and metastases from CT scans in the portal venous phase of enhancement. Fifty-six
      CT sections from 51 patients were used as representative of common hypodense
      liver lesions, including 22 simple cysts, 11 hemangiomas, 22 metastases, and 1
      image containing both a cyst and a hemangioma. The detection algorithm uses
      intensity-based histogram methods to find central lesions, followed by liver
      contour refinement to identify peripheral lesions. The classification algorithm
      operates on the focal lesions identified during detection, and includes shape
      based segmentation, edge pixel weighting, and lesion texture filtering. Support
      vector machines are then used to perform a pair-wise lesion classification. For
      the detection algorithm, 80% lesion sensitivity was achieved at approximately 0.3
      false positives (FP) per slice for central lesions, and 0.5 FP per slice for
      peripheral lesions, giving a total of 0.8 FP per section. For 90% sensitivity,
      the total number of FP rises to about 2.2 per section. The pair-wise
      classification yielded good discrimination between cysts and metastases (at 95%
      sensitivity for detection of metastases, only about 5% of cysts are incorrectly
      classified as metastases), perfect discrimination between hemangiomas and cysts,
      and was least accurate in discriminating between hemangiomas and metastases (at
      90% sensitivity for detection of hemangiomas, about 28% of metastases were
      incorrectly classified as hemangiomas). Initial implementations of our algorithms
      are promising for automating liver lesion detection and classification.

PMID- 15487743
TI  - Relationship between the generalized equivalent uniform dose formulation and the
      Poisson statistics-based tumor control probability model.
AB  - The generalized equivalent uniform dose (GEUD) model uses a power-law formalism,
      where the outcome is related to the dose via a power law. We herein investigate
      the mathematical compatibility between this GEUD model and the Poisson statistics
      based tumor control probability (TCP) model. The GEUD and TCP formulations are
      combined and subjected to a compatibility constraint equation. This compatibility
      constraint equates tumor control probability from the original heterogeneous
      target dose distribution to that from the homogeneous dose from the GEUD
      formalism. It is shown that this constraint equation possesses a unique,
      analytical closed-form solution which relates radiation dose to the tumor cell
      survival fraction. It is further demonstrated that, when there is no positive
      threshold or finite critical dose in the tumor response to radiation, this
      relationship is not bounded within the realistic cell survival limits of 0%-100%.
      Thus, the GEUD and TCP formalisms are, in general, mathematically inconsistent.
      However, when a threshold dose or finite critical dose exists in the tumor
      response to radiation, there is a unique mathematical solution for the tumor cell
      survival fraction that allows the GEUD and TCP formalisms to coexist, provided
      that all portions of the tumor are confined within certain specific dose ranges.

PMID- 15487744
TI  - Optimization of dose distributions for bifurcated coronary vessels treated with
      catheter-based photon and beta emitters using the simulated annealing algorithm.
AB  - The dose distributions in the bifurcated vessels treated with a catheter-based
      delivery system are complicated by the geometry of bifurcation consisting of a
      main and a branch vessel at different angles, and it is difficult to generate
      satisfactory dose distributions. We hypothesize that increasing the number of
      dwell positions can result in better dose distributions. An optimization method
      based on the simulated annealing was developed to demonstrate the validity of
      this idea. In this method, the source in the branch treatment was allowed to take
      up to five dwell positions. A cost function was constructed to deliver the
      prescription dose to the planning targets with penalties for both overdosing and
      underdosing. By using the optimization algorithm, it was found that for 90
      degrees to 60 degrees bifurcated vessels an optimized single dwell position
      treatment scheme can be as effective as the schemes that include up to five dwell
      positions. As the bifurcation angle becomes smaller than 60 degrees, the dose
      distributions generated with the single dwell position scheme become less
      satisfactory than the more complicated treatment schemes with multiple dwell
      positions. By using a three-dwell-position treatment scheme for the 192Ir source,
      the overdosing can be kept under 166% even at a bifurcation angle of 20 degrees.

PMID- 15487745
TI  - An inverse-geometry volumetric CT system with a large-area scanned source: a
      feasibility study.
AB  - We propose an inverse-geometry volumetric CT system for acquiring a 15-cm volume
      in one rotation with negligible cone-beam artifacts. The system uses a large-area
      scanned source and a smaller detector array. This note describes two feasibility
      investigations. The first examines data sufficiency in the transverse planes. The
      second predicts the signal-to-noise ratio (SNR) compared to a conventional
      scanner. Results showed sufficient sampling of the full volume in less than 0.5 s
      and, when compared to a conventional scanner operating at 24 kW with a 0.5-s
      voxel illumination time (e.g., 0.5-s gantry rotation and pitch of one), predicted
      a relative SNR of 76%.

PMID- 15487746
TI  - Modelling of metastatic cure after radionuclide therapy: influence of tumor
      distribution, cross-irradiation, and variable activity concentration.
AB  - The objective was to study the influence of tumor number and size, cross
      irradiation from normal tissue, and of variable activity concentration on
      metastatic cure after radionuclide therapy. A model to calculate the metastatic
      cure probability (MCP) was developed, in which it was assumed that the tumor
      response was an exponential function of the absorbed dose. All calculations were
      performed for monoenergetic electron emitters with different energies (10-1000
      keV). The influence of tumor size and number of tumors were investigated with
      different log uniform distributions; the basic tumor distribution consisted of
      tumors with 1, 10, ..., 10(11) cells. The influence of cross-irradiation was
      assessed by calculating MCP for various tumor-to-normal tissue activity
      concentration ratios (TNC). The influence of variable activity concentration
      between tumors was calculated by assuming that the activity concentration in
      tumors was an inverse power law function of tumor mass. The required activity
      concentration (C0.9) and absorbed dose (D0.9) to obtain MCP=0.9 was calculated in
      the different models. The C0.9 and D0.9 needed to obtain MCP were very high; more
      than 25 MBq/g and 80 Gy, respectively. The lowest C0.9 and D0.9 for equal
      activity concentration in the different tumor sizes were obtained for electron
      energies less than 80 keV. For higher energies the low absorbed energy fraction
      in small tumors will increase the required C0.9 and D0.9 markedly. Cross
      irradiation from normal cells surrounding the tumor will cause sterilization of
      the smallest tumors and decrease the required C0.9 and D0.9 for higher electron
      energies. Assuming that the activity concentration decreased with increased tumor
      mass caused a marked increase in C0.9 and D0.9 in favor of higher electron
      energies. With the MCP model we demonstrated significant influence of the number
      of tumors, their size, TNC and variable activity concentration on MCP. The
      results are valuable when evaluating optimal choices for radionuclides for
      internal-emitter therapy.

PMID- 15487747
TI  - A comparison of reconstruction algorithms for breast tomosynthesis.
AB  - Three algorithms for breast tomosynthesis reconstruction were compared in this
      paper, including (1) a back-projection (BP) algorithm (equivalent to the shift
      and-add algorithm), (2) a Feldkamp filtered back-projection (FBP) algorithm, and
      (3) an iterative Maximum Likelihood (ML) algorithm. Our breast tomosynthesis
      system acquires 11 low-dose projections over a 50 degree angular range using an a
      Si (CsI:Tl) flat-panel detector. The detector was stationary during the
      acquisition. Quality metrics such as signal difference to noise ratio (SDNR) and
      artifact spread function (ASF) were used for quantitative evaluation of
      tomosynthesis reconstructions. The results of the quantitative evaluation were in
      good agreement with the results of the qualitative assessment. In patient
      imaging, the superimposed breast tissues observed in two-dimensional (2D)
      mammograms were separated in tomosynthesis reconstructions by all three
      algorithms. It was shown in both phantom imaging and patient imaging that the BP
      algorithm provided the best SDNR for low-contrast masses but the conspicuity of
      the feature details was limited by interplane artifacts; the FBP algorithm
      provided the highest edge sharpness for microcalcifications but the quality of
      masses was poor; the information of both the masses and the microcalcifications
      were well restored with balanced quality by the ML algorithm, superior to the
      results from the other two algorithms.

PMID- 15487748
TI  - Radial gradient-based segmentation of mammographic microcalcifications: observer
      evaluation and effect on CAD performance.
AB  - Precise segmentation of microcalcifications is essential in the development of
      accurate mammographic computer-aided diagnosis (CAD) schemes. We have designed a
      radial gradient-based segmentation method for microcalcifications, and compared
      it to both the region-growing segmentation method currently used in our CAD
      scheme and to the watershed segmentation method. Two observer studies were
      conducted to subjectively evaluate the proposed segmentation method. The first
      study (A) required observers to rate the segmentation accuracy on a 100-point
      scale. The second observer evaluation (B) was a preference study in which
      observers selected their preferred method from three displayed segmentation
      methods. In study A, the observers gave an average accuracy rating of 88 for the
      radial gradient-based and 50 for the region-growing segmentation method. In study
      B, the two observers selected the proposed method 56% and 62% of the time. We
      also investigated the effect of the proposed segmentation method on the
      performance of computerized classification scheme in differentiating malignant
      from benign clustered microcalcifications. The performances of the classification
      scheme using a linear discriminant analysis (LDA) or a Bayesian artificial neural
      network classifier both showed statistically significant improvements when using
      the proposed segmentation method. The areas under the receiver-operating
      characteristic curves for case-based performance when using the LDA classifier
      were 0.86 with the proposed segmentation method, 0.80 with the region-growing
      method, and 0.83 with the watershed method.

PMID- 15487749
TI  - An implantable radiation dosimeter for use in external beam radiation therapy.
AB  - An implantable radiation dosimeter for use with external beam therapy has been
      developed and tested both in vitro and in canines. The device uses a MOSFET
      dosimeter and is polled telemetrically every day during the course of therapy.
      The device is designed for permanent implantation and also acts as a radiographic
      fiducial marker. Ten dogs (companion animals) that presented with spontaneous,
      malignant tumors were enrolled in the study and received an implant in the tumor
      CTV. Three dogs received an additional implant in collateral normal tissue.
      Radiation therapy plans were created for the animals and they were treated with
      roughly 300 cGy daily fractions until completion of the prescribed cumulative
      dose. The primary endpoints of the study were to record any adverse events due to
      sensor placement and to monitor any movement away from the point of placement. No
      adverse events were recorded. Unacceptable device migration was experienced in
      two subjects and a retention mechanism was developed to prevent movement in the
      future. Daily dose readings were successfully acquired in all subjects. A
      rigorous in vitro calibration methodology has been developed to ensure that the
      implanted devices maintain an accuracy of +/-3.5% relative to an ionization
      chamber standard. The authors believe that an implantable radiation dosimeter is
      a practical and powerful tool that fosters individualized patient QA on a daily
      basis.

PMID- 15487750
TI  - An automatic seed finder for brachytherapy CT postplans based on the Hough
      transform.
AB  - PURPOSE: The purpose of the work is to describe a new algorithm for the automatic
      detection of implanted radioactive seeds within the prostate. The algorithm is
      based on the traditional Hough transform. A method of quality assurance is
      described as well as a quantitative phantom study to determine the accuracy of
      the algorithm. METHODS AND MATERIALS: An algorithm is described which is based on
      the Hough transform. The Hough transform is a well known transform traditionally
      used to automatically segment lines and other well defined geometric objects from
      images. The traditional Hough transform is extended to three-dimensions and
      applied to CT images of seed implanted prostate glands. A method based on
      digitally reconstructed radiographs is described to quality assure the determined
      three-dimensional positions of the detected seeds. Two phantom studies utilizing
      eight seeds and nine seeds are described. All eight seeds form a contiguous a
      square while the nine seed phantom describes seeds which are placed side-by-side
      in groups of two and three. The algorithm is applied to the CT scans of both
      phantoms and the seed positions determined. RESULTS: The algorithm has been
      commercially developed and used to perform postsurgical dosimetric assessment on
      approximately 1000 patients. Using the described quality assurance tool it was
      determined that the algorithm accurately determined the seed positions in all
      1000 patients. The algorithm was also applied to the eight seed phantom. The
      algorithm successfully found all eight seeds as well as their seed coordinates.
      The average radial error was determined to be 0.9 mm. For the nine seed phantom,
      the algorithm correctly identified all nine seeds, with an average radial error
      of 3 mm. CONCLUSIONS: The described algorithm is a robust, accurate, automatic,
      three-dimensional application for CT based seed determination.

PMID- 15487751
TI  - Radiation dose estimate in small animal SPECT and PET.
AB  - Calculations of radiation dose are important in assessing the medical and
      biological implications of ionizing radiation in medical imaging techniques such
      as SPECT and PET. In contrast, radiation dose estimates of SPECT and PET imaging
      of small animals are not very well established. For that reason we have estimated
      the whole-body radiation dose to mice and rats for isotopes such as 18F, 99mTc,
      201Tl, (111)In, 123I, and 125I that are used commonly for small animal imaging.
      We have approximated mouse and rat bodies with uniform soft tissue equivalent
      ellipsoids. The mouse and rat sized ellipsoids had a mass of 30 g and 300 g,
      respectively, and a ratio of the principal axes of 1:1:4 and 0.7:1:4. The
      absorbed fractions for various photon energies have been calculated using the
      Monte Carlo software package MCNP. Using these values, we then calculated MIRD S
      values for two geometries that model the distribution of activity in the animal
      body: (a) a central point source and (b) a homogeneously distributed source, and
      compared these values against S-value calculations for small ellipsoids tabulated
      in MIRD Pamphlet 8 to validate our results. Finally we calculated the radiation
      dose taking into account the biological half-life of the radiopharmaceuticals and
      the amount of activity administered. Our calculations produced S-values between
      1.06 x 10(-13) Gy/Bq s and 2.77 x 10(-13) Gy/Bq s for SPECT agents, and 15.0 x
      10(-13) Gy/Bq s for the PET agent 18F, assuming mouse sized ellipsoids with
      uniform source distribution. The S-values for a central point source in an
      ellipsoid are about 10% higher than the values obtained for the uniform source
      distribution. Furthermore, the S-values for mouse sized ellipsoids are
      approximately 10 times higher than for the rat sized ellipsoids reflecting the
      difference in mass. We reviewed published data to obtain administered
      radioactivity and residence times for small animal imaging. From these values and
      our computed S-values we estimated that the whole body dose in small animals
      ranges between 6 cGy and 90 cGy for mice and between about 1 cGy and 27 cGy for
      rats. The whole body dose in small animal imaging can be very high in comparison
      to the lethal dose to mice (LD50/30 approximately 7 Gy). For this reason the dose
      in small animal imaging should be monitored carefully and the administered
      activity should be kept to a minimum. These results also underscore the need of
      further development of instrumentation that improves detection efficiency and
      reduces radiation dose in small animal imaging.

PMID- 15487752
TI  - Fundamental imaging characteristics of a slot-scan digital chest radiographic
      system.
AB  - Our purpose in this study was to evaluate the fundamental image quality
      characteristics of a new slot-scan digital chest radiography system (ThoraScan,
      Delft Imaging Systems/Nucletron, Veenendaal, The Netherlands). The linearity of
      the system was measured over a wide exposure range at 90, 117, and 140 kVp with
      added Al filtration. System uniformity and reproducibility were established with
      an analysis of images from repeated exposures. The modulation transfer function
      (MTF) was evaluated using an established edge method. The noise power spectrum
      (NPS) and the detective quantum efficiency (DQE) of the system were evaluated at
      the three kilo-voltages over a range of exposures. Scatter fraction (SF)
      measurements were made using a posterior beam stop method and a geometrical chest
      phantom. The system demonstrated excellent linearity, but some structured
      nonuniformities. The 0.1 MTF values occurred between 3.3-3.5 mm(-1). The
      DQE(0.15) and DQE(2.5) were 0.21 and 0.07 at 90 kVp, 0.18 and 0.05 at 117 kVp,
      and 0.16 and 0.03 at 140 kVp, respectively. The system exhibited remarkably lower
      SFs compared to conventional full-field systems with anti-scatter grid, measuring
      0.13 in the lungs and 0.43 in the mediastinum. The findings indicated that the
      slot-scan design provides marked scatter reduction leading to high effective DQE
      (DQEeff) of the system and reduced patient dose required to achieve high image
      quality.

PMID- 15487753
TI  - New x-ray tube performance in computed tomography by introducing the rotating
      envelope tube technology.
AB  - The future demands of computed tomography imaging regarding the x-ray source can
      be summarized with higher scan power, shorter rotation times, shorter cool down
      times and smaller focal spots. We report on a new tube technology satisfying all
      these demands by making use of a novel cooling principle on one hand and of a
      novel beam control system on the other hand. Nowadays tubes use a rotating anode
      disk mainly cooled via radiation. The Straton x-ray tube is the first tube
      available for clinical routine utilizing convective cooling exclusively. It is
      demonstrated that this cooling principle makes large heat storage capacities of
      the anode disk obsolete. The unprecedented cooling rate of 4.8 MHU/min eliminates
      the need for waiting times due to anode cooling in clinical workflow. Moreover,
      an electronic beam deflection system for focal spot position and size control
      opens the door to advanced applications. The physical backgrounds are discussed
      and the technical realization is presented. From this discussion the superior
      suitability of this tube to withstand g-forces well above 20 g created by fast
      rotating gantries will become evident. Experience from a large clinical trial is
      reported and possible ways for future developments are discussed.

PMID- 15487754
TI  - Automatic detection of linear artifacts in medical images.
AB  - Our purpose in this study is to describe an algorithm for the automatic detection
      of linear artifacts in medical images. Linear artifacts arise as a result of many
      different forms of tissues and tissue boundaries within the imaging volume.
      Additionally, linear artifacts can arise for artificial structures such as
      radioactive seeds and radioactive linear sources. It is the purpose of the
      described algorithm to automatically detect linear artifacts of a certain length
      and diameter. The algorithm was written and compiled on a Pentium-4 based
      computer in the Microsoft Visual C/C++ language. Inert coils supplied by Radiomed
      Inc. were implanted into a standard prostate ultrasound phantom. Transaxial
      ultrasound images of the implanted phantom were obtained at 2 mm increments. The
      coded algorithm was then applied to the ultrasound imaging volume to
      automatically segment out the implanted coils. Thirteen coils were implanted in
      the prostate phantom. Thirteen coils were automatically identified in the imaging
      volume. An algorithm was developed to automatically determine the position and
      orientation of radioactive coils within an imaging volume. The algorithm
      successfully identified thirteen coils implanted in an ultrasound prostate
      phantom.

PMID- 15487755
TI  - Incorporating model parameter uncertainty into inverse treatment planning.
AB  - Radiobiological treatment planning depends not only on the accuracy of the models
      describing the dose-response relation of different tumors and normal tissues but
      also on the accuracy of tissue specific radiobiological parameters in these
      models. Whereas the general formalism remains the same, different sets of model
      parameters lead to different solutions and thus critically determine the final
      plan. Here we describe an inverse planning formalism with inclusion of model
      parameter uncertainties. This is made possible by using a statistical analysis
      based frameset developed by our group. In this formalism, the uncertainties of
      model parameters, such as the parameter a that describes tissue-specific effect
      in the equivalent uniform dose (EUD) model, are expressed by probability density
      function and are included in the dose optimization process. We found that the
      final solution strongly depends on distribution functions of the model
      parameters. Considering that currently available models for computing biological
      effects of radiation are simplistic, and the clinical data used to derive the
      models are sparse and of questionable quality, the proposed technique provides us
      with an effective tool to minimize the effect caused by the uncertainties in a
      statistical sense. With the incorporation of the uncertainties, the technique has
      potential for us to maximally utilize the available radiobiology knowledge for
      better IMRT treatment.

PMID- 15487756
TI  - Implementation of the DPM Monte Carlo code on a parallel architecture for
      treatment planning applications.
AB  - We have parallelized the Dose Planning Method (DPM), a Monte Carlo code optimized
      for radiotherapy class problems, on distributed-memory processor architectures
      using the Message Passing Interface (MPI). Parallelization has been investigated
      on a variety of parallel computing architectures at the University of Michigan
      Center for Advanced Computing, with respect to efficiency and speedup as a
      function of the number of processors. We have integrated the parallel pseudo
      random number generator from the Scalable Parallel Pseudo-Random Number Generator
      (SPRNG) library to run with the parallel DPM. The Intel cluster consisting of 800
      MHz Intel Pentium III processor shows an almost linear speedup up to 32
      processors for simulating 1 x 10(8) or more particles. The speedup results are
      nearly linear on an Athlon cluster (up to 24 processors based on availability)
      which consists of 1.8 GHz+ Advanced Micro Devices (AMD) Athlon processors on
      increasing the problem size up to 8 x 10(8) histories. For a smaller number of
      histories (1 x 10(8)) the reduction of efficiency with the Athlon cluster (down
      to 83.9% with 24 processors) occurs because the processing time required to
      simulate 1 x 10(8) histories is less than the time associated with interprocessor
      communication. A similar trend was seen with the Opteron Cluster (consisting of
      1400 MHz, 64-bit AMD Opteron processors) on increasing the problem size. Because
      of the 64-bit architecture Opteron processors are capable of storing and
      processing instructions at a faster rate and hence are faster as compared to the
      32-bit Athlon processors. We have validated our implementation with an in-phantom
      dose calculation study using a parallel pencil monoenergetic electron beam of 20
      MeV energy. The phantom consists of layers of water, lung, bone, aluminum, and
      titanium. The agreement in the central axis depth dose curves and profiles at
      different depths shows that the serial and parallel codes are equivalent in
      accuracy.

PMID- 15487757
TI  - Role of copper in tumour angiogenesis--clinical implications.
AB  - The formation of new blood vessels is the initial step in progressive tumour
      development and metastasis. The first stage in tumour angiogenesis is the
      activation of endothelial cells. Copper ions stimulate proliferation and
      migration of endothelial cells. It has been shown that serum copper concentration
      increases as the cancer disease progresses and correlates with tumour incidence
      and burden. Copper ions also activate several proangiogenic factors, e.g.,
      vascular endothelial growth factor, basic fibroblast growth factor, tumour
      necrosis factor alpha and interleukin 1. This review concerns a brief
      introduction into the basics of tumour blood vessel development as well as the
      regulatory mechanisms of this process. The role of copper ions in tumour
      angiogenesis is discussed. The new antiangiogenic therapies based on a reduction
      of copper levels in tumour microenvironment are reviewed.

PMID- 15487758
TI  - Analytical product study of germanium-containing medicine by different ICP-MS
      applications.
AB  - For several years organo-germanium containing medicine has been used for special
      treatments of e.g. cancer and AIDS. The active substances contain germanium as
      beta-carboxyethylgermanium sesquioxide ((GeCH2CH2COOH)203/"Ge-132"),
      spirogermanium, germanium-lactate-citrate or unspecified forms. For humans,
      germanium is not essential and in general the toxicity of the mentioned organo
      germanium compounds is low. Acute and chronic toxic effects of inorganic
      germanium dioxide have been demonstrated. It is obvious that especially inorganic
      germanium has a higher potential of negative effects. Therefore, a widespread
      analytical product control is indispensable. Inductively coupled plasma mass
      spectrometry (ICP-MS) is the preferred technique and different applications were
      developed for controlling various parameters: (i) A speciation method using high
      performance liquid chromatography (HPLC) coupled with quadrupole (Q-) ICP-MS was
      developed for the identification of organo-germanium species in medicine. (ii)
      The nuclear magnetic resonance (NMR) technique was applied to confirm the
      molecular structure and to determine the molecule concentration. (iii) The total
      concentration of germanium in the medicine was determined in the diluted sample
      by high resolution (HR-) ICP-MS. (iv) For a general overview, a multi-element
      screening method of 56 elements with HR-ICP-MS was developed. The semi
      quantitative mode was used for quantification and elements of higher abundance
      are reported. (v) Investigations about matrix-based interferences on masses of
      isotopes, which are generally determinable without remarkable problems. Isotopes
      like e.g. 85Rb, 88Sr, 89y, 90Zr, 93Nb and the isotopes of Ba are strongly
      interfered by different Ge-based molecules and need to be analysed in a higher
      resolution mode than used for other common matrices.

PMID- 15487759
TI  - Zinc status and bone mineralisation in adolescent girls.
AB  - The aim of the project was to assess the relationship between zinc status and
      bone mineralisation in pre-menarcheal adolescent girls. One hundred and thirty
      nine healthy pre-menarcheal girls (Tanner pubic hair stage < or = 4), aged 12.4
      +/- 1.0 years, had two visits at an interval of 2 years. Serum and urine zinc
      concentrations (Zn S; Zn U; Zn U/ creatinine), insulin-like growth factor 1 (IGF
      I), and markers of bone turn-over, i.e. osteocalcin and parathormone (PTH),
      concentrations were measured at the first visit. Lumbar (L2-L4) bone mineral
      content and density (BMC, BMD) were measured at both visits. BMC and BMD and
      their increase at the follow-up after 2 years were compared with biochemical data
      by multiple regression. The stage of puberty was added as a covariable in the
      analysis. At the first visit, a significant correlation was found between sexual
      maturity and initial BMC, BMD, height, weight, and IGF-I. Zn S was negatively
      correlated with osteocalcin. Zn U showed a positive correlation with BMC, BMD,
      IGF-I, height, weight, and PTH. At the second visit, sexual maturity showed a
      positive correlation with BMD and weight increments and a negative one with BMC
      and height gains. Zn S was significantly related with BMD increase. These
      correlations suggest that zinc plays a role in normal growth and bone
      mineralisation during puberty onset.

PMID- 15487760
TI  - Insulin sensitising action of chromium picolinate in various experimental models
      of diabetes mellitus.
AB  - Although chromium is an essential element for carbohydrate and lipid metabolism,
      its effects in diabetic patients are still debated. We have studied the effect of
      6 week treatment with chromium picolinate (8 microg/ml in drinking water) in
      streptozotocin (STZ)-induced type 1 and type 2 diabetic rat models. The mechanism
      of anti-diabetic action of chromium picolinate was studied using C2C12 myoblasts
      and 3T3-L1 adipocytes. Chromium picolinate significantly decreased the area under
      the curve over 120 min for glucose of both STZ-induced type 1 (40mg/kg, i.v. in
      adult rats) and type 2 (90 mg/kg, i.p. in 2 day old rat neonates) diabetic rats
      without any significant change in area under the curve over 120 min for insulin
      as compared to controls. The composite insulin sensitivity index and insulin
      sensitivity index (KITT) values of both type 1 and type 2 diabetic rats were
      increased significantly by chromium picolinate. Treatment with chromium
      picolinate produced a significant decrease in elevated cholesterol and
      triglyceride levels in both types of diabetic rats. In 3T3-L1 adipocytes,
      chromium picolinate (0-10 micromol) per se did not produce any effect, however,
      when co-incubated with insulin it significantly increased the intracellular
      triglyceride synthesis (EC50 = 363.7nmol/1). Similarly in C2C12 myoblasts,
      chromium picolinate alone did not produce any effect, however, it significantly
      increased insulin-induced transport of 14C-glucose. In conclusion, chromium
      picolinate significantly improves deranged carbohydrate and lipid metabolism of
      experimental chemically induced diabetes in rats. The mechanism of in vivo anti
      diabetic action appears to be peripheral (skeletal muscle and adipose tissue)
      insulin enhancing action of chromium.

PMID- 15487761
TI  - Effect of different doses of chromium picolinate on protein metabolism in infant
      rats.
AB  - This 12-day study was conducted to evaluate the effects of three different levels
      of dietary chromium (100, 200, and 500 microg/day) in the form of chromium
      picolinate (CrPic) on growth and protein use in weaned rats. No significant
      effect of CrPic on body weight gain, food intake, or food conversion rate was
      observed. Elevated doses of CrPic seemed to increase muscle mass, either by
      stimulating protein anabolism by activation of insulin by chromium or by lowering
      protein degradation. However, these effects had no repercussions on overall
      growth, suggesting that any anabolic effect of chromium due to the action of
      insulin was probably marginal.

PMID- 15487762
TI  - Elevated caspase-3 and Fas mRNA expression in jejunum of adult rats during
      subclinical zinc deficiency.
AB  - The programmed cell death-so-called apoptosis-is a physiological process
      occurring in all multicellular organisms to control cell-number homeostasis.
      Nevertheless, increase of apoptotic cell death in different organs can lead to
      pathological alterations. As zinc is a potent inhibitor of apoptosis, we
      investigated the influence of zinc deficiency on mRNA expression levels of
      caspase-3 and Fas in adult rats. For this purpose, 24 adult rats fed a Zn
      deficient diet for up to 29 days were compared to seven animals in the control
      group. After 1, 2, 4, 7, 11, 16, 22 and 29 days of treatment three animals were
      sacrificed (n = 24). Total RNA extraction from thymus, liver, jejunum and colon
      was carried out. Samples were reverse transcribed and subjected to real-time PCR.
      Relative quantification of caspase-3 and Fas mRNA expression was achieved on the
      basis of normalisation by glycerolaldehyd-3-phosphate-dehydrogenase mRNA
      expression levels in all samples. In jejunum, up to day 11 the relative mRNA
      expression of the respective genes decreased. A significant increase in caspase-3
      and Fas expression was found from day 11 of zinc deficiency onward. In contrast,
      mRNA expression in liver and colon remained unaffected, whereas thymus showed a
      slight but not significant increase in the expression of these genes. This study
      provides the first evidence that even moderate zinc deficiency in an adult, non
      growing rat model is able to elevate mRNA expression levels of factors involved
      in early stages of apoptosis.

PMID- 15487763
TI  - Chromium-yeast supplementation of chicken broilers in an industrial farming
      system.
AB  - The experiment was performed on ISA broilers at big farm conditions. One day old
      chickens were randomly assigned to two poultry-houses with the capacity of 10600
      birds each. Chromium was provided in the form of chromium enriched yeast (1.0 g
      Cr/kg yeast) given in doses of 0.2 mg Cr/kg diet. No significant differences in
      growth rate and only a slight decrease of feed conversion ratio was found in
      broilers receiving chromium-yeast supplement. However, these birds had a lower
      mortality rate comparied with the rate observed in the controls. Moreover,
      dietary chromium led also to an improvement of carcass composition. Organic
      chromium supplementation increased the weight of pectoral muscles and meat of
      these broilers contained less amounts of fat and cholesterol. These effects were
      accompanied by an insignificant increase of chromium concentration in the
      pectoral muscles of birds fed chromium supplemented diets, from 40 to 52
      microg/kg wet tissue.

PMID- 15487764
TI  - Regional accumulation of aluminium in the rat brain is affected by dietary
      vitamin E.
AB  - The regional accumulation of aluminium in the brain of male albino Wistar rats
      was investigated following 4 weeks of administration by intraperitoneal injection
      of aluminium lactate (10mg aluminium/kg body weight). The consequences of
      concomitant dietary vitamin E (5, 15, or 20 mg vitamin E/g of food) were also
      studied. Rat brains were dissected into functional regions, for the measurement
      of aluminium and markers of oxidative stress. Plasma aluminium levels were
      increased in all groups of animals receiving aluminium lactate (p < 0.01), and
      these levels were significantly reduced in rats receiving concomitant vitamin E
      (p < 0.05). In the group of rats receiving aluminium alone, levels of brain
      tissue aluminium were increased in all regions of brain examined (p< 0.01). Brain
      tissue aluminium levels were reduced by concomitant dietary vitamin E. Catalase
      and reduced glutathione levels were both reduced in several regions of brain in
      animals treated with aluminium (p < 0.05). Aluminium treatment was not associated
      with a significant increase in reactive oxygen species (ROS) generation (p >
      0.05), although ROS production was attenuated by dietary vitamin E (p < 0.05) in
      some regions.

PMID- 15487765
TI  - Effect of dietary organic versus inorganic selenium in laying hens on the
      productivity, selenium distribution in egg and selenium content in blood, liver
      and kidney.
AB  - We investigated the effect of organic versus inorganic dietary selenium in laying
      hens on the productivity, selenium distribution in egg and selenium content in
      blood, liver and kidney. Sixty Leghorn laying hens were fed a basic diet
      containing 0.23mg Se/kg DM (dry matter) for 2 weeks and then were allocated
      randomly into three groups. Thereafter, the hens were given the same basic diet
      without supplementation, or with 0.51 mg Se/kg DM as sodium selenite (SS) or Se
      malt (SM). During the experiment, egg rate and dietary intake were recorded,
      blood was sampled on days 10 and 20, and six eggs were sampled on days 8, 16 and
      24 from each treatment group for Se content determination. At the end of the
      experiment, 10 hens from each treatment were slaughtered, and liver and kidney
      were sampled for the determination of Se content. The result showed that with the
      increase of dietary Se level, the Se content in egg, blood, liver and kidney was
      elevated (P < 0.05), but the hens' productivity was not affected. SS increased
      liver Se content more than SM (P < 0.05), while the Se content both in blood and
      kidney did not differ significantly between the SS and SM treatments. Se from SM
      and SS mainly deposited in the egg yolk. This suggests that the metabolic route
      of Se from SM is similar to that of Se from SS in laying hens.

PMID- 15487766
TI  - A report of high-dose selenium supplementation: response and toxicities.
AB  - Concerns about the toxicity of selenium has limited the doses used in
      chemoprevention. Based on previous studies, intakes of 400 microg/day and plasma
      selenium of 1000 ng/ml (Dietary Reference Intakes, Academy Press, New York, 2000,
      p. 384) were established as the no observed adverse effect level (NOAEL). This
      investigation summarizes the plasma response and toxicity reports from 24 men
      with biopsy-proven prostate cancer who were randomized to either 1600 or 3200
      microg/day of selenized yeast as part of a controlled clinical trial testing
      selenium as a chemopreventive agent for prostate cancer progression. Subjects
      were on these doses for averages of almost 12 months. Plasma selenium levels were
      monitored throughout the course of follow-up. Symptoms of selenium toxicity were
      assessed by patient interview with specific questions regarding breath, hair and
      nail changes. Several liver and kidney function tests and hematology were
      measured at 6-month intervals. 8 subjects were randomized to the 1600 microg/day
      and 16 to the 3200 microg/day group. The mean plasma selenium levels achieved
      with supplementation were 492.2 ng/ml (SD = 188.3) and 639.7 ng/ml (SD = 490.7)
      for the 1600 and 3200 microg/ day doses, respectively. The 3200 microg/day group
      reported more selenium-related side effects. Blood chemistry and hematology
      results were all within normal limits for both treatment groups. More subjects on
      3200 microg/day reported symptoms of selenium toxicity; however, these reports
      did not correspond to peaks in plasma selenium levels. We observed no obvious
      selenium-related serious toxicities. As selenium is used in more chemoprevention
      and therapeutic settings, additional information on selenium species,
      sequestration of selenium in specific organs, excretion, and toxicities is
      needed.

PMID- 15487767
TI  - Stable isotope-enriched selenite and selenate tracers for human metabolic
      studies: a fast and accurate method for their preparation from elemental selenium
      and their identification and quantification using hydride generation atomic
      absorption spectrometry.
AB  - Stable isotope tracers are safe and nutritionally relevant tools for the
      investigation of mineral metabolism in man. Increased research into the
      functional role of selenium has resulted in a need for well-characterised,
      isotopically enriched solutions of the element in order to determine the
      nutritional relevance of selenium fortification of foods. A simple method for the
      conversion of isotopically enriched elemental selenium (2.5-10 mg) into selenite
      and selenate, and their accurate characterisation and quantification is
      described. Analysis of selenite and selenate tracers using continuous-flow
      hydride generation-atomic absorption spectrometry technique was based on the
      specificity of the selenium hydride reaction and allowed their precise (RSD<2.5%)
      and accurate determination in aqueous solutions. The detection and determination
      limits were at 0.13 and 0.36 microg Se/l, respectively. Isotopically enriched
      elemental selenium was converted into selenite and selenate by a nitric acid and
      a combined nitric acid/hydrogen peroxide oxidation, respectively. The conversion
      was quantitative (>95%) and specific for both inorganic selenocompounds. Selenite
      and selenate labels were stable in 0.1 mol/l nitric acid for at least 18 months,
      i.e. making them ideally suitable for use in long-term metabolic studies. An
      overview of data relating to the absorption and retention of selenium by humans
      obtained using the two, well-characterised, tracers is presented and indicates
      that selenite and selenate are equally well retained in adult men and infants,
      despite differences in their absorption and urinary excretion characteristics.

PMID- 15487768
TI  - Effects of dietary selenium on glutathione peroxidase and thioredoxin reductase
      activity and recovery from cardiac ischemia-reperfusion.
AB  - Glutathione peroxidase and thioredoxin reductase are selenocysteine-dependent
      enzymes that protect against oxidative injury. This study examined the effects of
      dietary selenium on the activity of these two enzymes in rats, and investigated
      the ability of selenium to modulate myocardial function post ischemia
      reperfusion. Male wistar rats were fed diets containing 0, 50, 240 and 1000
      microg/kg sodium selenite for 5 weeks. Langendorff perfused hearts isolated from
      these rats were subjected to 22.5 min global ischemia and 45 min reperfusion,
      with functional recovery assessed. Liver samples were collected at the time of
      sacrifice, and heart and liver tissues assayed for thioredoxin reductase and
      glutathione peroxidase activity. Selenium deficiency reduced the activity of both
      glutathione peroxidase and thioredoxin reductase systemically. Hearts from
      selenium deficient animals were more susceptible to ischemia-reperfusion injury
      when compared to normal controls (38% recovery of rate pressure product (RPP) vs.
      47% recovery of RPP). Selenium supplementation increased the endogenous activity
      of thioredoxin reductase and glutathione peroxidase and resulted in improved
      recovery of cardiac function post ischemia reperfusion (57% recovery of RPP).
      Endogenous activity of glutathione peroxidase and thioredoxin reductase is
      dependent on an adequate supply of the micronutrient selenium. Reduced activity
      of these antioxidant enzymes is associated with significant reductions in
      myocardial function post ischemia-reperfusion.

PMID- 15487769
TI  - Effects of selenium deficiency on fatty acid metabolism in rats fed fish oil
      enriched diets.
AB  - The hepatic fatty acid metabolism was investigated in rats stressed by selenium
      deficiency and enhanced fish oil intake. Changes in the composition of lipids,
      peroxides, and fatty acids were studied in the liver of rats fed either a
      Sedeficient (8 microg Se/kg) or a Se-adequate (300 microg Se/kg) diet, both rich
      in n-3 fatty acid-containing fish oil (100 g/kg diet) and vitamin E (146 mg alpha
      tocopherol/kg diet). The two diets were identical except for their Se content. Se
      deficiency led to a decrease in hair coat density and quality as well as to
      changes in liver lipids, individual lipid fractions and phospholipid fatty acid
      composition of the liver. The low Se status did reduce total and reduced
      glutathione in the liver but did not affect the hepatic malondialdehyde level. In
      liver phospholipids (PL), Se deficiency significantly reduced levels of palmitic
      acid [16:0], fatty acids of the n-3 series such as DHA [22:6 n-3], and other long
      chain polyunsaturates C-20-C-22, but increased n-6 fatty acids such as linoleic
      acid (LA) [18:2 n-6]. Thus, the conversion of LA to arachidonic acid was reduced
      and the ratio of n-6/n-3 fatty acids was increased. As in liver PL, an increase
      in the n-6/n-3 ratio was also observed in the mucosal total fatty acids of the
      small intestine. These results suggest that in rats with adequate vitamin E and
      enhanced fish oil intake, Se deficiency affects the lipid concentration and fatty
      acid composition in the liver. The changes may be related to the decreased levels
      of selenoenzymes with antioxidative functions. Possible effects of Se on
      absorption, storage and desaturation of fatty acids were also discussed.

PMID- 15487770
TI  - Comparison of the serum selenium content of healthy adults living in the Antwerp
      region (Belgium) with recent literature data.
AB  - Graphite furnace atomic absorption spectrometry, after improved matrix
      modification and using Zeeman background correction, was used to measure the
      serum selenium content of healthy adults living in the Antwerp region (Belgium).
      The mean serum concentration of 13 men and 13 women, sampled once a month during
      1 year, was 84.3 +/- 9.4ng/ml with a broad range of 51.4-121.7 ng/ml. The intra
      individual variation was remarkably high. Recent literature on selenium
      concentrations is reviewed and values are tabulated, with limitation to healthy
      adults and European countries. The mean serum selenium concentration measured
      corresponded well to older literature data for Belgium. The obtained values were
      found to be in the medium range compared with the literature data for other
      European countries.

PMID- 15487771
TI  - Antioxidant effect of vitamin E and selenium on lipid peroxidation, enzyme
      activities and biochemical parameters in rats exposed to aluminium.
AB  - Aluminium has the potential to be neurotoxic in humans and animals, and is
      present in many manufactured foods and medicines and is also added to drinking
      water for purification purposes. Therefore, the present study was carried out to
      investigate (1) the alterations in biochemical parameters, free radicals and
      enzyme activities induced by aluminium chloride (AlCl3) in plasma and different
      tissues of male rats, and (2) the role of vitamin E (VE) and selenium in
      alleviating the negative effects of aluminium. VE plays an important role as an
      antioxidant and is consequently expected to protect tissues from damage caused by
      reactive oxygen metabolites. Selenium is also generally recognized to be a trace
      mineral of great importance for human health, protecting the cells from the
      harmful effects of free radicals. Seven rats per group were assigned to one of
      six treatment groups: 0 mg VE, 0 mg Se and 0 mg AlCl3/kg body weight (BW)
      (control); 100 mg VE/kg BW; 200 microg Se kg BW; 34 mg AlCl3/kg BW (1/25 LD50);
      34 mg AlCl3 plus 100 mg VE/kg BW; 34 mg AlCl3 plus 200 microg Se/kg BW. Rats were
      orally administered their respective doses every other day for 30 days.
      Evaluations were made for lipid peroxidation, enzyme activities and biochemical
      parameters. Results obtained showed that AlCl3 significantly (p<0.05) induced
      free radicals (thiobarbituric acid-reactive substances) and decreased the
      activity of glutathione S-transferase (GST) and the levels of sulphydryl groups
      (SH groups) in rat plasma, liver, brain, testes and kidney. Aspartate
      aminotransferase, alanine aminotransferase, alkaline phosphatase, acid
      phosphatase, and phosphorylase activities were significantly decreased in liver
      and testes due to AlCl3 administration, while the activities of these enzymes
      were significantly increased in plasma. In addition, plasma, liver, testes and
      brain lactate dehydrogenase activities were significantly increased. On the
      contrary, the activity of acetylcholinesterase was significantly decreased in
      brain and plasma. Al treatment caused a significant decrease in plasma total
      protein (TP), albumin and total lipids (TL), and increased the concentrations of
      glucose, urea, creatinine, bilirubin and cholesterol. VE or Se alone
      significantly decreased the levels of free radicals, TL, cholesterol, urea and
      bilirubin, and increased the activity of GST, and SH groups, TP and albumin,
      while the rest of the tested parameters were not affected. VE or Se in
      combination with Al partially or totally alleviated its toxic effects on the
      studied parameters. In conclusion, VE and Se have beneficial effects and could be
      able to antagonize Al toxicity.

PMID- 15487772
TI  - More chloramine complications.

PMID- 15487773
TI  - Microarrays monitor environmental contaminants.

PMID- 15487774
TI  - Tracking America's exported air pollution.

PMID- 15487775
TI  - Experimenting with hydroelectric reservoirs.

PMID- 15487776
TI  - Internal metal sequestration and its ecotoxicological relevance: a review.
AB  - Organisms are able to control metal concentrations in certain tissues of their
      body to minimize damage of reactive forms of essential and nonessential metals
      and to control selective utilization of essential metals. These physiological
      aspects of organisms are not accounted for when assessing the risk of metals in
      the environment. The Critical Body Residue (CBR) approach relates toxicity to
      bioaccumulation and biomagnification and might at first sight provide a more
      accurate estimation of effects than the external concentration. When expressing
      CBRs on total internal concentrations, the capacity of organisms to sequester
      metals in forms that are not biologically reactive is neglected. The
      predictability of toxic effects will increase when knowledge on metal
      compartmentalization within the organisms' body is taken into account. Insight in
      metal compartmentalization sheds light on the different accumulation strategies
      organisms can follow upon metal exposure. Using a fractionation procedure to
      isolate metal-rich granules and tissue fragments from intracellular and cytosolic
      fractions, the internal compartmentalization of metals can be approximated. In
      this paper, current knowledge regarding metal compartmentalization in organisms
      is summarized, and metal fractions are identified that are indicators of
      toxicity. Guidance is provided on future improvement of models, such as the
      Biotic Ligand Model (BLM), for risk assessment of metal stress to biota.

PMID- 15487777
TI  - Chemical and biological characterization of newly discovered iodoacid drinking
      water disinfection byproducts.
AB  - Iodoacid drinking water disinfection byproducts (DBPs) were recently uncovered in
      drinking water samples from source water with a high bromide/iodide concentration
      that was disinfected with chloramines. The purpose of this paper is to report the
      analytical chemical identification of iodoacetic acid (IA) and other iodoacids in
      drinking water samples, to address the cytotoxicity and genotoxicity of IA in
      Salmonella typhimurium and mammalian cells, and to report a structure-function
      analysis of IA with its chlorinated and brominated monohalogenated analogues. The
      iodoacid DBPs were identified as iodoacetic acid, bromoiodoacetic acid, (Z)- and
      (E)-3-bromo-3-iodopropenoic acid, and (E)-2-iodo-3-methylbutenedioic acid. IA
      represents a new class (iodoacid DBPs) of highly toxic drinking water
      contaminants. The cytotoxicity of IA in S. typhimurium was 2.9x and 53.5x higher
      than bromoacetic acid (BA) and chloroacetic acid (CA), respectively. A similar
      trend was found with cytotoxicity in Chinese hamster ovary (CHO) cells; IA was
      3.2x and 287.5x more potent than BA and CA, respectively. This rank order was
      also expressed in its genotoxicity with IA being 2.6x and 523.3x more mutagenic
      in S. typhimurium strain TA100 than BA and CA, respectively. IA was 2.0x more
      genotoxic than BA and 47.2x more genotoxic than CA in CHO cells. The rank order
      of the toxicity of these monohalogenated acetic acids is correlated with the
      electrophilic reactivity of the DBPs. IA is the most toxic and genotoxic DBP in
      mammalian cells reported in the literature. These data suggest that chloraminated
      drinking waters that have high bromide and iodide source waters may contain these
      iodoacids and most likely other iodo-DBPs. Ultimately, it will be important to
      know the levels at which these iodoacids occur in drinking water in order to
      assess the potential for adverse environmental and human health risks.

PMID- 15487778
TI  - Effect of storage on the isotopic composition of nitrate in bulk precipitation.
AB  - Stable isotopic analysis of atmospheric nitrate is increasingly employed to study
      nitrate sources and transformations in forested catchments. Large volumes have
      typically been required for delta18O and delta15N analysis of nitrate in
      precipitation due to relatively low nitrate concentrations. Having bulk
      collectors accumulate precipitation over an extended time period allows for
      collection of the required volume as well as reducing the total number of
      analyses needed to determine the isotopic composition of mean annual nitrate
      deposition. However, unfiltered precipitation left in collectors might be subject
      to microbial reactions that can alter the isotopic signature of nitrate in the
      sample. Precipitation obtained from the Turkey Lakes Watershed was incubated
      under conditions designed to mimic unfiltered storage in bulk precipitation
      collectors and monitored for changes in nitrate concentration, delta15N, and
      delta18O. Results of this experiment indicated that no detectable nitrate
      production or assimilation occurred in the samples during a two-week incubation
      period and that atmospheric nitrate isotopic ratios were preserved. The ability
      to collect unfiltered precipitation samples for an extended duration without
      alteration of nitrate isotope ratios is particularly useful at remote study sites
      where daily retrieval of samples may not be feasible.

PMID- 15487779
TI  - Assessment of sulfate sources in high-elevation Asian precipitation using stable
      sulfur isotopes.
AB  - Stable sulfur isotope measurements (delta34S) made on samples collected from a 2
      m snowpit on the Inilchek Glacier, Tien Shan Mountains (42.16 degrees N, 80.25
      degrees E, 5100 m) are used to estimate sources of sulfate (SO4(2-)) in high
      elevation Central Asian precipitation. Comparison of snowpit oxygen isotope
      (delta18O) data with previous work constrains the age of the snowpit samples to
      the summer season during which they were retrieved (1999). Delta34S measurements
      were made at 10 cm resolution (20 samples total), with delta34S values ranging
      from 0.4/1000 during background ([SO4(2-)] < 1 microequiv L(-1)) periods to
      19.4/1000 during a single high [SO4(2-)] event. On the basis of the significant
      correlation (r = 0.87) between [SO4(2-)] and delta34S values, coupled with major
      ion concentration time series and concentration ratios, we suggest a two
      component mixing system consisting of evaporite dust and anthropogenic SO4(2-) to
      explain the observed delta34S values. Using a regression model, we estimate that
      during the 1999 summer season 60% of the deposited SO4(2-) was from an evaporite
      dust source, while 40% of the SO4(2-) was from anthropogenic sources. Due to the
      potentially large and unconstrained range of delta34S values for both evaporite
      and anthropogenic SO4(2-) sources in Asia, the error in our estimates is
      difficult to assess. However, the delta34S data from the 1999 Tien Shan snowpit
      provide the first unambiguous identification of evaporite and anthropogenic SO4(2
      ) in high-elevation Asian precipitation, and future ice core studies using
      improved analysis techniques and source delta34S values can provide detailed
      information on sulfur biogeochemistry and anthropogenic impacts in Asian alpine
      regions.

PMID- 15487780
TI  - Polychlorinated dibenzo-p-dioxin/polychlorinated dibenzofuran releases into the
      atmosphere from the use of secondary fuels in cement kilns during clinker
      formation.
AB  - The aim of this study was to evaluate the influence of using waste materials,
      such as tires or meat meal, as a secondary fuel during clinker production on the
      polychlorinated dibenzo-p-dioxin (PCDD)/polychlorinated dibenzofuran (PCDF)
      emission levels to the atmosphere. For this purpose, three different cement
      plants in Spain were chosen to conduct the project in different sampling
      episodes. Different materials were separately evaluated in each plant: the first
      plant included the addition of meat meal in the kiln, the second plant used
      rejected tires, and the third plant used a mixture of both. In all cases, PCDD/F
      emission values remained below the limit established by the European Union
      Directive of 0.1 ng I-TEQ/Nm3, with values ranging from 0.001 to 0.042 ng I
      TEQ/Nm3. The major contribution to total TEQ in the majority of cases came from
      2,3,7,8-tetrachlorodibenzofuran owing to its relatively higher levels and
      2,3,4,7,8-pentachlorodibenzofuran because of its TEF of 0.5. The remaining 15
      toxic congeners collectively provided only a minor contribution to TEQ.
      Furthermore, no marked differences were found compared with reported data
      obtained from Spanish cement kiln plants using conventional fuel. This fact
      indicates that the addition of used tires or meat meals had no effect on
      PCDD/PCDF emission levels.

PMID- 15487781
TI  - Historical records of airborne polycyclic aromatic hydrocarbons by analyzing
      dated corks of the bark pocket in a Longpetiole Beech tree.
AB  - Historical monitoring of airborne polycyclic aromatic hydrocarbons (PAHs)
      pollution levels was novelly demonstrated by analyzing the dated corks of a bark
      pocket formed from 1873 to 2003 in a Longpetiole Beech (Fagus longipetiolata)
      tree trunk sampled from southeastern China. The fundamental studies indicated
      that the PAHs of log K(oa) < 8.5 are primarily accumulated through interactions
      with lipid substances in cork and log K(oa) dependent, while the PAHs of log
      K(oa) > 8.5 existing as particle-phase dependent on log Vp are accumulated
      through stochastic entrapment by the lenticels on the surface of the cork. The
      translocation of PAHs by xylem flow and phloem stream as well as radial diffusion
      from the cork to the inner tissues was not significant, and the cork is most
      effective for accumulating airborne PAHs. The total concentrations of 16 EPA PAHs
      (sumPAHs) in the dated corks progressively increased from 43.5 ng/g recorded in
      the earliest available cork in 1873-1875 to the maximum 345.7 ng/g in 1956-1961,
      and then gradually decreased to 267.0 ng/g in 2003, while the concentration of
      perylene (PER) was slightly fluctuating at 0.178 +/- 0.033 ng/g. Moreover, the
      concentration ratio of sumPAHs to PER increased from 193 to 2431 from 1873 to
      2003, indicating a progressive increase in PAH pollution in southeastern China.

PMID- 15487782
TI  - pH dependence of carbon tetrachloride reductive dechlorination by magnetite.
AB  - Magnetite is precipitated by dissimilatory iron-reducing bacteria or forms
      through corrosion of zero-valent iron (ZVI) in permeable reactive barriers.
      Reduction of carbon tetrachloride (CCl4) by synthetic magnetite was examined in
      batch reactors to evaluate the pH dependence of the reaction rates and product
      distributions. This work presents the first data where magnetite promotes CCl4
      dechlorination independent of added sorbed Fe(II) or coexisting minerals that
      maintained Fe2+ above the magnetite solubility limit. In this system, reaction
      rate constants increase with increasing pH values between 6 and 10. The pH
      dependence is explained by acid-base equilibrium between two surface sites, where
      the more deprotonated exhibits greater dechlorination reactivity. The
      distribution of reaction products was also found to depend on pH. The primary
      reaction product is carbon monoxide (CO) followed by chloroform (CHCl3). CHCl3
      production is at a minimum at pH 6 but increases through pH 10. Formation rate
      constants for both products increase with increasing pH, but the values for CHCl3
      increase at a much faster rate. A hypothesis is proposed that relates the CHCl3
      rate enhancement to the reduced capacity of deprotonated surface sites to
      stabilize the trichlorocarbanion transition-state complex. These data form a
      basis to assess the natural attenuation capacity of magnetite formed under iron
      reducing conditions. Application of this information to permeable barrier
      technology suggests that, in the long term, oxidation of ZVI to magnetite may be
      accompanied by a shift toward more benign reaction products as well as a 2 order
      of magnitude decrease in reaction rate constants.

PMID- 15487783
TI  - Biocatalytic synthesis of polycatechols from toxic aromatic compounds.
AB  - A process is described in which toxic aromatic compounds are converted by toluene
      dioxygenase and in turn toluene cis-dihydrodiol dehydrogenase to catechols which
      are further polymerized by peroxidase-catalyzed oxidation producing
      polycatechols. Three approaches for obtaining catechols were employed: (1)
      addition of halogenated aromatics to P. putida F1, resulting in the accumulation
      of halogenated catechols; (2) inhibition of catechol 2,3-dioxygenase of P. putida
      F1 by known aromatic and aliphatic inhibitors; and (3) overexpression of toluene
      dioxygenase and toluene cis-dihydrodiol dehydrogenase genes in E. coli JM109. The
      process is suitable for producing novel catechols that upon oxidation may yield
      polymers with unique properties, presenting a tool for producing tailor-made
      biopolymers. Formation of 3-chlorocatechol from chlorobenzene, 3,4
      dichlorocatechol from 1,2-dichlorobenzene, and catechol from benzene and their
      subsequent oxidation and polymerization was demonstrated. Oxidation of catechol
      yielded polymers with molecular weights of up to 4000 Daltons. Their apparently
      high water solubility eliminates the need for water-miscible solvents. In aqueous
      solution oxidation of catechols was rapid, yet the presence of 20%, 30%, and 40%
      ethanol, resulted in a rate decrease of 31%, 95%, and 93%, respectively. The
      advantage is that significantly less peroxidase is required for performing the
      reactions if miscible solvents are not employed. Furthermore, water-soluble
      polymers may be desirable for many applications.

PMID- 15487784
TI  - XAS study of mercury(II) ions trapped in mercaptan-functionalized mesostructured
      silicate with a wormhole framework structure.
AB  - Directly assembled wormhole mesostructures with high level functionalized
      mercaptan (MP-HMS) have been shown to be effective mercury(II) (Hg2+) trapping
      agents. Sorption of Hg2+ onto MP-HMS was investigated using X-ray absorption
      spectroscopy (XAS) to identify the structural coordination of the adsorbed Hg.
      Samples with different fractions of mercaptan functionalized groups (i.e., x =
      0.1 and 0.5) with various Hg/S molar ratios ranging from 0.05 to 1.4 were
      investigated. XAS analysis indicates that adsorbed Hg first coordination shell is
      best fitted with an Hg-O path and an Hg-S path. The Hg-S atomic distance (R(Hg
      S)) remained relatively constant while the Hg-S coordination numbers (CN)
      decreased as Hg/S loading increased. For the Hg-O path, both the CN and the R(Hg
      O) increased with increasing Hg loading. XAS results suggest that at low Hg
      loadings, adsorbed Hg2+ forms mostly monodentate sulfur complexes (-S-Hg-OH) with
      the sulfur functional groups on the MP-HMS surfaces. At high Hg loadings, the Hg
      coordination environment is consistent with the formation of a double-layer
      structure of Hg attached to sulfur binding sites (-S-Hg-O-Hg-OH).

PMID- 15487785
TI  - Aquatic hypoxia is a teratogen and affects fish embryonic development.
AB  - Hypoxia occurs over large areas in aquatic systems worldwide, and there is
      growing concern that hypoxia may affect aquatic animals, leading to population
      decline and changes in community by elimination of sensitive species. For the
      first time, we report that sublethal levels of hypoxia can significantly increase
      (+77.4%) malformation in fish embryonic development. Disruption of apoptotic
      pattern was clearly evident at 24 h post-fertilization, which may be a major
      cause of malformation. Furthermore, embryonic development was delayed, and
      balance of sex hormones (testosterone and estradiol) was disturbed during
      embryonic stages, implicating that subsequent sexual development may also be
      affected. Overall, our results imply that hypoxia may have a teratogenic effect
      on fish and delay fish embryonic development, which may subsequently impair
      species fitness leading to natural population decline.

PMID- 15487786
TI  - Comparative evaluation of chloroethene dechlorination to ethene by
      Dehalococcoides-like microorganisms.
AB  - Reductive dehalogenation of tetrachloroethene (PCE), trichloroethene (TCE), cis
      1,2-dichloroethene (DCE), and vinyl chloride (VC) was examined in four cultures
      containing Dehalococcoides-like microorganisms. Dechlorination and growth
      kinetics were compared using a Monod growth-rate model for multiple electron
      acceptor usage with competition. Included were the Victoria mixed culture
      containing Dehalococcoides species strain VS (from Victoria, TX), the mixed
      culture KB-1/VC (from southern Ontario), the Pinellas mixed culture (from
      Pinellas, FL), and D. ethenogenes strain 195. All cultures, with the exception of
      D. ethenogenes strain 195, grew with VC as catabolic electron acceptor. A
      dilution method was developed that allows a valid comparison to be made of
      dehalogenating kinetics between different mixed cultures. Using this procedure,
      maximum growth rates on VC were found to be similar for strain VS and KB-1/VC
      (0.42-0.49 +/- 0.02 d(-1)) but slower for the Pinellas culture (0.28 +/- 0.01 d(
      1)). The 16S rRNA gene sequences were determined to ensure that no cross
      contamination between cultures had occurred. Following enrichment of the VC
      dechlorinating microorganisms on VC, the cultures were amended with DCE, TCE, or
      PCE. The three mixed cultures failed to dechlorinate PCE or did so very slowly.
      However, the dilution technique indicated that all experienced growth on TCE and
      DCE as well as on VC. Maximum growth rates on DCE alone were quite similar (0.43
      0.46 d(-1)), while the Pinellas culture grew faster on TCE alone (0.49 d(-1))
      than did the other two mixed cultures (0.33-0.35 d(-1)). Half-velocity and
      inhibition constants for growth on TCE were also determined for the three mixed
      cultures; both constants were found to be essentially equal and the same for the
      different cultures, varying between only 8.6 and 10.5 microM. The ability of the
      strain VS, KB-1/VC, and Pinellas cultures to utilize TCE rapidly with conversion
      to ethene is quite different from that of any other reported microorganism. It
      was separately confirmed with more traditional cell-counting techniques that
      strain VS coupled TCE, as well as DCE and VC, utilization with growth. This is
      the first report of an organism obtaining energy for growth through every step in
      the reduction of TCE to ethene. Also, as suggested by the dilution technique, the
      dehalogenating organisms in the KB-1/VC and Pinellas cultures appear to obtain
      growth from TCE utilization as well. Such ability to grow while dehalogenating
      TCE to ethene will be an important advantage for their use in bioaugmentation.

PMID- 15487787
TI  - Pathway dependent isotopic fractionation during aerobic biodegradation of 1,2
      dichloroethane.
AB  - 1,2-Dichloroethane (1,2-OCA) is a widespread groundwater contaminant known to be
      biodegradable under aerobic conditions via enzymatic oxidation or hydrolytic
      dehalogenation reactions. Current literature reports that stable carbon isotope
      fractionation of 1,2-DCA during aerobic biodegradation is large and reproducible
      (-27 to -33/1000). In this study, a significant variation in the magnitude of
      stable carbon isotope fractionation during aerobic biodegradation was observed.
      Biodegradation in experiments involving microcosms, enrichment cultures, and pure
      microbial cultures produced a consistent bimodal distribution of enrichment
      factors (epsilon) with one mean epsilon centered on -3.9 +/- 0.6/1000 and the
      other on -29.2 +/- 1.9/1000. Reevaluation of epsilon in terms of kinetic isotope
      effects 12k/13k gave values of 12k/13k = 1.01 and 1.06, which are typical of
      oxidation and hydrolytic dehalogenation (S(N)2) reactions, respectively. The
      bimodal distribution is therefore consistent with the microbial degradation of
      1,2-DCA by two separate enzymatic pathways. This interpretation is further
      supported in this study by experiments with pure strains of Xanthobacter
      autotrophicus GJ10, Ancylobacter aquaticus AD20, and Pseudomonas sp. Strain DCA1
      for which the enzymatic degradation pathways are well-known. A small
      fractionation of -3.0/1000 was measured for 1,2-DCA degradation by Pseudomonas
      sp. Strain DCA1 (monooxygenase enzyme), while degradation by the hydrolytic
      dehalogenase enzyme by the other two pure strains was characterized by
      fractionation of -32.3/1000.

PMID- 15487788
TI  - Spectroscopic evidence for Fe(II)-Fe(III) electron transfer at the iron oxide
      water interface.
AB  - Using the isotope specificity of 57Fe Mossbauer spectroscopy, we report
      spectroscopic observations of Fe(II) reacted with oxide surfaces under conditions
      typical of natural environments (i.e., wet, anoxic, circumneutral pH, and about
      1% Fe(II)). Mossbauer spectra of Fe(II) adsorbed to rutile (TiO2) and aluminum
      oxide (Al2O3) show only Fe(II) species, whereas spectra of Fe(II) reacted with
      goethite (alpha-FeOOH), hematite (alpha-Fe2O3), and ferrihydrite (Fe5HO8)
      demonstrate electron transfer between the adsorbed Fe(II) and the underlying
      iron(III) oxide. Electron-transfer induces growth of an Fe(III) layer on the
      oxide surface that is similar to the bulk oxide. The resulting oxide is capable
      of reducing nitrobenzene (as expected based on previous studies), but
      interestingly, the oxide is only reactive when aqueous Fe(II) is present. This
      finding suggests a novel pathway for the biogeochemical cycling of Fe and also
      raises important questions regarding the mechanism of contaminant reduction by
      Fe(II) in the presence of oxide surfaces.

PMID- 15487789
TI  - Investigation of interparticle forces in natural waters: effects of adsorbed
      humic acids on iron oxide and alumina surface properties.
AB  - The nature of interparticle forces acting on colloid particle surfaces with
      adsorbed surface films of the internationally used humic acid standard material,
      Suwannee River Humic Acid (SHA), has been investigated using an atomic force
      microscope (AFM). Two particle surfaces were used, alumina and a hydrous iron
      oxide film coated onto silica particles. Adsorbed SHA dominated the interactive
      forces for both surface types when present. At low ionic strength and pH > 4, the
      force curves were dominated by electrostatic repulsion of the electrical double
      layers, with the extent of repulsion decreasing as electrolyte (NaCl)
      concentration increased, scaling with the Debye length (kappa(-1)) of the
      electrolyte according to classical theory. At pH approximately 4, electrostatic
      forces were largely absent, indicating almost complete protonation of carboxylic
      acid (-COOH) functional groups on the adsorbed SHA. Under these conditions and
      also at high electrolyte concentration ([NaCl] > 0.1 M), the absence of
      electrostatic forces allowed observation of repulsion forces arising from steric
      interaction of adsorbed SHA as the oxide surfaces approached closely to each
      other (separation < 10 nm). This steric barrier shrank as electrolyte
      concentration increased, implying tighter coiling of the adsorbed SHA molecules.
      In addition, adhesive bridging between surfaces was observed only in the presence
      of SHA films, implying a strong energy barrier to spontaneous detachment of the
      surfaces from each other once joined. This adhesion was especially strong in the
      presence of Ca2+ which appears to bridge SHA layers on each surface. Overall, our
      results show that SHA is a good model for the NOM adsorbed on colloids.

PMID- 15487790
TI  - Insights into the chemistry of new particle formation and growth events in
      Pittsburgh based on aerosol mass spectrometry.
AB  - New particle formation and growth events have been observed in several urban
      areas and are of concern due to their potential negative effects on human health.
      The main purpose of this study was to investigate the chemistry of ultrafine
      particles during the growth phase of the frequently observed nucleation events in
      Pittsburgh (approximately 100 events per year) and therefore infer the mechanisms
      of new particle growth in the urban troposphere. An Aerodyne aerosol mass
      spectrometer (AMS) and two SMPS systems were deployed at the U.S. EPA Pittsburgh
      Supersite during September 2002. Significant nucleation events were observed in 3
      out of the 16 days of this deployment, including one of the 10 strongest
      nucleation events observed in Pittsburgh over a period of 15 months. These events
      appear to be representative of the climatology of new particle formation and
      growth in the Pittsburgh region. Distinctive growth of sulfate, ammonium,
      organics, and nitrate in the ultrafine mode (33-60 nm in a vacuum aerodynamic
      diameter or approximately 18-33 nm in physical diameter) was observed during each
      of these three events, with sulfate always being the first (and the fastest)
      species to increase. Ultrafine ammonium usually increased 10-40 min later than
      sulfate, causing the ultrafine mode particles to be more acidic during the
      initial stages of the nucleation events. Significant increase of ultrafine
      organics often happened after 11:00 a.m., when photochemistry is more intense.
      This observation coupled with a parallel increase of ultrafine m/z 44, a mass
      fragment generally representative of oxygenated organic compounds, indicates that
      secondary organic species contribute significantly to the growth of particles at
      a relatively later time of the event. Among all these four species, nitrate was
      always a minor component of the ultrafine particles and contributed the least to
      the new particle growth.

PMID- 15487791
TI  - Thermodynamic accounting of ecosystem contribution to economic sectors with
      application to 1992 U.S. economy.
AB  - Incorporation of ecological considerations in decision-making is essential for
      sustainable development, but is hindered by inadequate appreciation of the role
      of ecosystems, and lack of scientifically rigorous techniques for including their
      contribution. This paper develops a novel thermodynamic accounting framework for
      including the contribution of natural capital via thermodynamic input-output
      analysis. This framework is applied to the 1992 US economy comprising 91 industry
      sectors, resulting in delineation of the myriad ways in which sectors of the US
      economy rely on ecosystem products and services. The contribution of ecosystems
      is represented via the concept of ecological cumulative exergy consumption
      (ECEC), which is related to emergy analysis but avoids any of its controversial
      assumptions and claims. The use of thermodynamics permits representation of all
      kinds of inputs and outputs in consistent units, facilitating the definition of
      aggregate metrics. Total ECEC requirement indicates the extent to which each
      economic sector relies directly and indirectly on ecological inputs. The
      ECEC/money ratio indicates the relative monetary versus ecological throughputs in
      each sector, and indicates the relationship between the thermodynamic work needed
      to produce a product or service and the corresponding economic activity. This
      ratio is found to decrease along economic supply chains, indicating industries
      that are higher up in the economic food chain price ecosystem contribution more
      than the basic infrastructure industries such as mining and manufacturing. The
      ratio of CEC with and without inclusion of ecosystems indicates the extent to
      which conventional thermoeconomic analysis underestimates the contribution of
      ecosystems. Such ratios, made available for the first time, provide unique
      insight into the importance of natural capital, and are especially useful in
      hybrid thermodynamic life cycle analysis of industrial systems. The approach,
      data compiled in this work, and the resulting insight provide a more ecologically
      conscious tool for environmental decision-making, and has potential applications
      at micro as well as macro scales.

PMID- 15487792
TI  - Passive air sampling using semipermeable membrane devices at different wind
      speeds in situ calibrated by performance reference compounds.
AB  - Semipermeable membrane devices (SPMDs) are passive samplers used to measure the
      vapor phase of organic pollutants in air. This study tested whether extremely
      high wind-speeds during a 21-day sampling increased the sampling rates of
      polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), and
      whether the release of performance reference compounds (PRCs) was related to the
      uptakes at different wind-speeds. Five samplers were deployed in an indoor,
      unheated, and dark wind tunnel with different wind-speeds at each site (6-50 m s(
      1)). In addition, one sampler was deployed outside the wind tunnel and one
      outside the building. To test whether a sampler, designed to reduce the wind
      speeds, decreased the uptake and release rates, each sampler in the wind tunnel
      included two SPMDs positioned inside a protective device and one unprotected SPMD
      outside the device. The highest amounts of PAHs and PCBs were found in the SPMDs
      exposed to the assumed highest wind-speeds. Thus, the SPMD sampling rates
      increased with increasing wind-speeds, indicating that the uptake was largely
      controlled by the boundary layer at the membrane-air interface. The coefficient
      of variance (introduced by the 21-day sampling and the chemical analysis) for the
      air concentrations of three PAHs and three PCBs, calculated using the PRC data,
      was 28-46%. Thus, the PRCs had a high ability to predict site effects of wind and
      assess the actual sampling situation. Comparison between protected and
      unprotected SPMDs showed that the sampler design reduced the wind-speed inside
      the devices and thereby the uptake and release rates.

PMID- 15487793
TI  - Detecting N-nitrosamines in drinking water at nanogram per liter levels using
      ammonia positive chemical ionization.
AB  - Detection of N-nitrosamines in water supplies is an environmental and public
      health issue because many N-nitrosamines are classified as probable human
      carcinogens. Some analytical methods are inadequate for detecting N
      nitrosodimethylamine (NDMA) at low ng/L concentrations in water due to poor
      extraction efficiencies and nonselective and nondistinctive GC/MS electron
      ionization techniques. Development of a selective, sensitive, and affordable
      benchtop analytical method for eight N-nitrosamines, at relevant drinking water
      concentrations was the primary objective of this project. A solid-phase
      extraction method using Ambersorb 572 and LiChrolut EN was developed in
      conjunction with GC/MS ammonia positive chemical ionization (PCI). Ammonia PCI
      shows excellent sensitivity and selectivity for N-nitrosamines, which were
      quantified using both isotope dilution/surrogate standard and internal standard
      procedures. Method detection limits for all investigated N-nitrosamines ranged
      from 0.4 to 1.6 ng/L. Applying our extraction method to authentic drinking water
      samples with dissolved organic carbon concentrations of 9 mg/L, we were able to
      detect N-nitrosodimethylamine (2-180 ng/L) as well as N-nitrosopyrrolidine (2-4
      ng/L) and N-nitrosomorpholine (1 ng/L), two N-nitrosamines that have not been
      reported in drinking water to date. With high recoveries of standards and
      analytes, the described internal standard method offers a valuable new approach
      for investigating several N-nitroso compounds at ultratrace levels in drinking
      water.

PMID- 15487794
TI  - Solid-phase microextraction to predict bioavailability and accumulation of
      organic micropollutants in terrestrial organisms after exposure to a field
      contaminated soil.
AB  - The risk posed by soil contaminants strongly depends on their bioavailability. In
      this study, a partition-based sampling method was applied as a tool to estimate
      bioavailability in soil. The accumulation of organic micropollutants was measured
      in two earthworm species (Eisenia andrei and Aporrectodea caliginosa) and in 30
      microm poly(dimethylsiloxane) (PDMS)-coated solid-phase micro extraction (SPME)
      fibers after exposure to two field-contaminated soils. Within 10 days, steady
      state in earthworms was reached, and within 20 days in the SPME fibers. Steady
      state concentrations in both earthworm species were linearly related to
      concentrations in fibers over a 10,000-fold range of concentrations. Measured
      concentrations in earthworms were compared to levels calculated via equilibrium
      partitioning theory and total concentrations of contaminants in soil. In
      addition, freely dissolved concentrations of contaminants in pore water, derived
      from SPME measurements, were used to calculate concentrations in earthworms.
      Measured concentrations in earthworms were close to estimated concentrations from
      the SPME fiber measurements. Freely dissolved concentrations of contaminants in
      pore water, derived from SPME measurements, were used to calculate
      bioconcentration factors (BCF) in earthworms. A plot of log BCFs against the
      octanol-water partition coefficient (log Kow) was linear up to a log Kow of 8.
      These results show that measuring concentrations of hydrophobic chemicals in a
      PDMS-coated fiber represents a simple tool to estimate internal concentrations of
      chemicals in biota exposed to soil.

PMID- 15487795
TI  - Analysis of triclocarban in aquatic samples by liquid chromatography electrospray
      ionization mass spectrometry.
AB  - Triclocarban, N-(4-chlorophenyl)-N'-(3,4-dichlorophenyl)urea, is a
      polychlorinated phenyl urea pesticide, marketed under the trademark TCC and used
      primarily as an antibacterial additive in personal care products. Despite its
      extensive use over several decades, environmental occurrence data on TCC are
      scarce. This is due in part to a lack of analytical techniques offering the
      desired sensitivity, selectivity, affordability, and ease of use. This need is
      addressed here by introducing a liquid chromatography electrospray ionization
      mass spectrometry (LC/ESI/MS) method allowing for the determination of TCC
      concentrations in aquatic environments at the ng/L level. TCC was concentrated
      from aqueous samples by solid-phase extraction, separated from interferences on a
      C18 column by either isocratic or gradient elution, and detected and identified
      in negative ESI mode by selectively monitoring the (M - H)- base peak (m/z 313)
      and its 37Cl-containing isotopes (m/z 315, 317) that served as reference ions.
      Particulates contained in aquatic samples were extracted and analyzed separately.
      Accurate quantification was achieved using stable isotopes of TCC and triclosan
      as internal standards. Addition of 10 mM acetic acid to the mobile phase yielded
      acetic acid adducts ([M - H + 60]-) that were successfully exploited to boost
      method sensitivity and selectivity, especially when analyzing challenging
      environmental matrixes. Method detection limits were matrix dependent, ranging
      from 3 to 50 ng/L. In 36 grab samples obtained from the Greater Baltimore area,
      TCC was detected in river water and wastewater at concentrations of up to 5600
      and 6750 ng/L, respectively. Raw and finished drinking water did not contain
      detectable quantities of the pesticide (<3 ng/L). In conclusion, the new
      LC/ESI/MS method was applied successfully to collect environmental occurrence
      data on TCC in U.S. water resources. Study results suggest that the bacteriostat
      and pesticide is a frequent but currently underreported contaminant whose
      environmental fate and behavior deserve further scrutiny.

PMID- 15487796
TI  - Mechanisms and inorganic byproducts of trihalomethane compounds sonodegradation.
AB  - Organic pollutants can be sonodegraded by two pathways: pyrolysis, oxidation by
      free radicals, or the combination of both. The sonolytic degradation mechanisms
      and byproducts formation of aqueous trihalomethanes (THMs) were investigated at
      acoustic frequency of 20 kHz. The main sonodegradation mechanism of the
      chloroform, dichlorobromomethane, dibromochloromethane, and bromoform was found
      to be pyrolysis. The sonolysis degradation pathway of iodoform is free radicals
      oxidation. Hydrogen peroxide, nitrate, chloride, bromide, iodide, and iodate ions
      were detected and quantified as the inorganic products of the THMs sonication. A
      total of 48% TOC removal was achieved after a 180-min sonication of the THMs
      mixture.

PMID- 15487797
TI  - Reduction of hexavalent chromium with the brown seaweed Ecklonia biomass.
AB  - A new type of biomass, protonated brown seaweed Ecklonia sp., was used for the
      removal of Cr(VI). When synthetic wastewater containing Cr(VI) was placed in
      contact with the biomass, the Cr(VI) was completely reduced to Cr(III). The
      converted Cr(III) appeared in the solution phase or was partly bound to the
      biomass. The Cr(VI) removal efficiency was always 100% in the pH range of this
      study (pH 1 to approximately 5). Furthermore, the Cr(VI) reduction was
      independent of the Cr(III) concentration, the reaction product, suggesting that
      the reaction was an irreversible process under our conditions. Proton ions were
      consumed in the ratio of 1.15 +/- 0.02 mol of protons/mol of Cr(VI), and the rate
      of Cr(VI) reduction increased with decreasing the pH. An optimum pH existed for
      the removal efficiency of total chromium (Cr(VI) plus Cr(III)), but this
      increased with contact time, eventually reaching approximately pH 4 when the
      reaction was complete. The electrons required for the Cr(VI) reduction also
      caused the oxidation of the organic compounds in the biomass. One gram of the
      biomass could reduce 4.49 +/- 0.12 mmol of Cr(VI). From a practical viewpoint,
      the abundant and inexpensive Ecklonia biomass could be used for the conversion of
      toxic Cr(VI) into less toxic or nontoxic Cr(III).

PMID- 15487798
TI  - Activated carbon fiber cloth electrothermal swing adsorption system.
AB  - Capture and recovery of hazardous air pollutants (HAPs) and volatile organic
      compounds (VOCs) from gas streams using physical adsorption onto activated carbon
      fiber cloth (ACFC) is demonstrated on the bench-scale. This system is regenerated
      electrothermally, by passing an electric current directly through the ACFC. The
      adsorbate desorbs from the ACFC, rapidly condenses on the inside walls of the
      adsorber, and then drains from the adsorber as a pure liquid. Rapid
      electrothermal desorption exhibits such unique characteristics as extremely low
      purge gas flow rate, rapid rate of ACFC heating, rapid mass transfer kinetics
      inherent to ACFC, and in-vessel condensation. An existing system was scaled up
      500%, and the new system was modeled using material and energy balances.
      Adsorption isotherms using methyl ethyl ketone (MEK) and ACFC were obtained while
      electricity passed through the ACFC and at temperatures above MEK's boiling
      point. These isotherms agreed within 7% to Dubinin-Radushkevich modeled isotherms
      that were extrapolated from independently determined gravimetric measurements
      obtained at lower temperatures. Energy and material balances for the
      electrothermal desorption of organic vapors and ACFC agree to within 7% of
      experimentally measured values. These results allow the modeling of
      electrothermal desorption of organic vapors from gas streams with in-vessel
      condensation to optimize operating conditions of the system during regeneration
      of the adsorbent.

PMID- 15487799
TI  - Removal of industrial cutting oil from oil emulsions by polymeric ultra- and
      microfiltration membranes.
AB  - The utilization of micro- and ultrafiltration with polymeric membranes for
      treatment of industrial cutting oil emulsion was investigated. The performance of
      14 different membranes with pore sizes in the range of 1-800 nm, representing 8
      different materials and varying hydrophobicity, was determined experimentally.
      Membrane permeances between 1.6 and 939 L m 2 h(-1) bar(-1) have been observed
      for the different samples as well as oil rejections between 3.42% and 99.99%.
      Membrane pore size and contact angle showed little influence on both values,
      while an interesting correlation is displayed to the individual membranes'
      capillary pressures. A possible explanation for this phenomenon is suggested
      based on the formation of oil films on the membrane surface. From the
      investigated membranes, the best-suited one for cutting oil treatment was
      selected and subjected to further experiments. The effect of process temperatures
      between 22 and 43 degrees C and of feed oil concentrations between 0 and 20 vol %
      on the removal performance was determined. The results correspond to the
      explanation suggested previously.

PMID- 15487800
TI  - Nucleation mode formation in heavy-duty diesel exhaust with and without a
      particulate filter.
AB  - Particle size distribution measurement with direct tailpipe sampling is employed
      to study the effect of a continuously regenerating diesel particulate filter
      (CRDPF) on emissions of a heavy-duty diesel engine. The CRDPF consists of an
      oxidation catalyst and a filter. Tests are conducted using 2 and 40 ppm sulfur
      content fuels and two steady-state driving modes. The formation of nucleation
      mode with and without CRDPF is found to depend on different parameters. Without
      after-treatment, size distribution is observed to have a nucleation mode only at
      low load. Being independent of the fuel sulfur level (with these low sulfur level
      fuels), this nucleation mode is suggested to form mainly from hydrocarbons. With
      a CRDPF-equipped engine, nucleation mode, which was not observed without CRDPF,
      was found at high load mode only. This nucleation mode formation was found to
      correlate positively with fuel sulfur content. It is suggested that sulfuric acid
      is a main nucleating species in this situation, resulting from the effective
      conversion of SO2 to SO3 in the oxidation catalyst. Using a thermodenuder
      confirms that the nucleation mode particles are semivolatile in nature.

PMID- 15487801
TI  - Evaluation of a biologically active cover for mitigation of landfill gas
      emissions.
AB  - Landfills are the third largest source of anthropogenic CH4 in the United States,
      and there is potential for reduction in this source of greenhouse gases and other
      contaminants. The objective of this work was to contrast emissions of CH4 and non
      methane organic compounds (NMOCs) from landfill cells covered with soil or a
      biologically active cover consisting of yard waste compost. On the basis of four
      field campaigns over 14 months, CH4 emissions from the biocover (BC) varied from 
      1.73 to 1.33 g m(-2) d(-1), with atmospheric uptake measured in 52% of tests. BC
      emissions did not increase when the gas collection system was turned off. Uptake
      of atmospheric CH4 was measured in 54% of tests on the soil cover (SC) when the
      gas collection was system active and 12% when the gas collection system was off.
      Many (26%) relatively high fluxes (>15 g m(-2) d(-1)) were measured from the SC
      as were some dramatic effects due to deactivation of the gas collection system.
      In tests with positive emissions, stable isotope measurements showed that the BC
      and SC were responsible for oxidation of 55% and 21% of the CH4 reaching the
      bottom of the respective cover. Seven of the highest 10 NMOC emissions were
      measured in the SC, and 17 of 21 fluxes for speciated organic compounds were
      higher in the SC. The relationship between CH4, NMOC, and individual organic
      compound emissions suggested a correlation between CH4 and trace organic
      oxidation. BCs can reduce landfill gas emissions in the absence of a gas
      collection system and can serve as a polishing step in the presence of an active
      system.

PMID- 15487802
TI  - Cathode performance as a factor in electricity generation in microbial fuel
      cells.
AB  - Although microbial fuel cells (MFCs) generate much lower power densities than
      hydrogen fuel cells, the characteristics of the cathode can also substantially
      affect electricity generation. Cathodes used for MFCs are often either Pt-coated
      carbon electrodes immersed in water that use dissolved oxygen as the electron
      acceptor or they are plain carbon electrodes in a ferricyanide solution. The
      characteristics and performance of these two cathodes were compared using a two
      chambered MFC. Power generation using the Pt-carbon cathode and dissolved oxygen
      (saturated) reached a maximum of 0.097 mW within 120 h after inoculation
      (wastewater sludge and 20 mM acetate) when the cathode was equal size to the
      anode (2.5 x 4.5 cm). Once stable power was generated after replacing the MFC
      with fresh medium (no sludge), the Coulombic efficiency ranged from 63 to 78%.
      Power was proportional to the dissolved oxygen concentration in a manner
      consistent with Monod-type kinetics, with a half saturation constant of K(DO) =
      1.74 mg of O2/L. Power increased by 24% when the cathode surface areas were
      increased from 22.5 to 67.5 cm2 and decreased by 56% when the cathode surface
      area was reduced to 5.8 cm2. Power was also substantially reduced (by 78% to 0.02
      mW) if Pt was not used on the cathode. By using ferricyanide instead of dissolved
      oxygen, the maximum power increased by 50-80% versus that obtained with dissolved
      oxygen. This result was primarily due to increased mass transfer efficiencies and
      the larger cathode potential (332 mV) of ferricyanide than that obtained with
      dissolved oxygen (268 mV). A cathode potential of 804 mV (NHE basis) is
      theoretically possible using dissolved oxygen, indicating that further
      improvements in cathode performance with oxygen as the electron acceptor are
      possible that could lead to increased power densities in this type of MFC.

PMID- 15487803
TI  - Natural polysaccharides and their interactions with dye molecules: applications
      in effluent treatment.
AB  - Dyeing effluent is one of the largest contributors to textile effluent and such
      colored wastewater has a seriously destructive impact on the environment.
      Adsorption can be a very effective treatment for decolorization of textile dyeing
      effluent, but current techniques employ adsorption chemistry that is not
      particularly environmentally friendly, such as the use of alum. In this study,
      natural polysaccharides were used as adsorbents for removal of dye molecules from
      effluent. The results showed that naturally cationic polysaccharides such as
      chitin and chitosan gave excellent levels of color removal, and this was
      attributed to a combination of electrostatic attraction, van der Waals forces,
      and hydrogen bonding. Nonionic galactomannans (locust bean gum, guar gum, cassia
      gum) were also highly effective in removing dye from effluent, whereas other
      nonionic polysaccharides, such as starch, were not effective. This was attributed
      to the structure of the polysaccharides and the relative degree of inter- and
      intramolecular interactions between separate polymer chains. The pendant
      galactose residues of galactomannans prevented strong interaction, allowing
      greater hydrogen bonding with dye; comparatively, starch has extensive chain
      interactions, and as such had limited potential for hydrogen bonding with the dye
      molecules at the temperature of application. In addition, hydrophobic
      interactions between the hydrophobic parts of the dye and the alpha-face of the
      pendant galactose residues may have contributed to the superior performance.
      Repulsion between anionic polysaccharides and the dye anions prevented any
      hydrogen bonding and as such pectin, carrageenans, and alginic acid were not
      effective in dye removal from effluent. The use of galactomannans derived from
      plants in this system presents a sustainable method of effluent treatment. The
      raw materials are derived from renewable plant sources and are available in
      tonnage quantities, the adsorption system itself is highly effective and does not
      involve any additional chemical input or treatment other than the use of the
      adsorbent, and the adsorption agents themselves are nontoxic and biodegradable.

PMID- 15487804
TI  - Comment on "Geographic sensitivity of fine particle mass to emissions of SO2 and
      NOx".

PMID- 15487805
TI  - Can St. John's wort trigger psychoses?
AB  - BACKGROUND: St. John's wort (SJW) is a popular herbal remedy often self
      prescribed for depressed mood. It has recently been associated with psychotic
      events. AIM: To systematically review the clinical evidence associating SJW with
      psychotic events. METHODS: Five electronic databases were searched for all
      relevant reports. Data were extracted according to predefined criteria. RESULTS:
      Seventeen case reports associated the use of SJW with psychotic events. In 12
      instances, the diagnosis was mania or hypomania. Causality is in most cases
      possible. In no case was a positive rechallenge reported. CONCLUSION: These case
      reports raise the possibility that SJW may trigger episodes of mania in
      vulnerable patients. Clinicians should be aware of this possibility and
      researchers should attempt to ascertain whether the association is causal.

PMID- 15487806
TI  - Effects of acetylsalicylic acid on ascorbic acid concentrations in plasma,
      gastric mucosa, gastric juice and urine--a double-blind study in healthy
      subjects.
AB  - OBJECTIVE: This study investigated concentrations of ascorbic acid (ASC) in
      gastric mucosa, gastric juice, urine and plasma in healthy subjects under steady
      state and fasted conditions with and without concomitant administration of
      acetylsalicylic acid (ASA). MATERIAL AND METHODS: This was a prospective,
      randomized, double-blind, parallel-group study in healthy subjects. It has
      assessed the effects of a 6-day administration of 0.8 g ASA or 0.48 g ASC, 3
      times daily and the combination of both on concentrations of ASC in gastric
      mucosa, gastric juice, urine and plasma. Treatments were switched after 6 days
      without any washout for assessment of compartment sensitivity to changes in study
      medication resulting in an overall 14-day study period. Each of the 3 treatment
      groups consisted of 15 subjects. RESULTS: ASC concentrations were highest in the
      gastric mucosa (251+/-11 microg/g), followed by gastric juice (29+/-6 microg/ml),
      plasma (10+/-0.2 microg/ml), and urine (5+/-1 microg/ml). On day 7, ASC
      concentrations in gastric mucosa, plasma and urine had increased in those groups
      receiving ASC and decreased in the group receiving ASA only. All differences were
      statistically significant and indicate an interaction with ASA. In gastric juice,
      differences in ASC concentrations between the treatment groups were not
      statistically significant between baseline and day 7. ASC concentrations in
      plasma were strongly correlated with corresponding ASC concentrations in gastric
      mucosa (r = 0.34) and urine (r = 0.83), as were ASC concentrations in gastric
      mucosa with ASC in urine (r = 0.28). CONCLUSIONS: The gastric mucosa is the
      largest depot of ASC in the human body with ASC concentrations 25 times higher
      than in plasma. In healthy subjects, clinically relevant doses of ASA reduced ASC
      concentrations in gastric mucosa by about 10% within 6 days resulting from
      antioxidative defense mechanisms. In patients with long-term ASA treatment or
      conditions with additional risks such as elderly subjects with unfavorable
      dietary conditions and impaired antioxidative protection, a protective adjunct
      administration of ASC appears to be beneficial.

PMID- 15487807
TI  - Inhibition of human liver and duodenum sulfotransferases by drugs and dietary
      chemicals: a review of the literature.
AB  - Sulfotransferase catalyzes the transfer of sulfate, donated by 3'
      phosphoadenosine-5'-phosphosulfate, to an acceptor substrate that may be a
      hydroxy group or an amine group. Man is exposed daily to drugs and dietary
      chemicals that can inhibit sulfotransferase activity. The aim of this study was
      to review the literature concerning the inhibition of sulfotransferases by drugs
      and dietary chemicals in the human liver and duodenum. The IC50 value of
      mefenamic acid for human liver phenol sulfotransferase (SULT 1A1) was 0.02 microM
      and for human liver catechol sulfotransferase (SULT1A3) 76 microM with a SULT
      1A3/SULT1A1 ratio for the IC50 of 3,800. Mefenamic acid is therefore a potent and
      selective inhibitor of human liver SULT1A1. The IC50 values of mefenamic acid for
      the sulfation rates of (-)-salbutamol and (-)-apomorphine were 4 orders of
      magnitude greater in the human duodenum than in the liver. Salicylic acid
      inhibited the sulfation of (-)-apomorphine in human liver with an IC50 of 54 gM
      but did not inhibit the sulfation of (-)-apomorphine in human duodenum.
      Quercetin, a flavonoid present in edible fruit, vegetable and wine, was a potent
      inhibitor of human liver SULT1A1 and estrogen sulfotransferase (EST) activities
      and the sulfation of resveratrol. Quercetin inhibited the sulfation of dopamine,
      (-)-salbutamol, minoxidil and paracetamol and the IC50 values were 1 - 2 orders
      of magnitude greater in human duodenum than in the liver. In conclusion,
      mefenamic acid, salicylic acid and quercetin inhibit SULT1A1 whereas SULT1A3 is
      relatively resistant to the inhibition by these compounds. Under particular
      circumstances, human duodenum sulfotransferase is more resistant than liver
      sulfotransferase to the inhibition by mefenamic acid, salicylic acid and
      quercetin.

PMID- 15487808
TI  - The MDR1 3435 polymorphism in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a multifactorial disease, the
      pathogenesis of which involves immunological, genetic and environmental factors.
      P-glycoprotein (P-gp) encoded by the MDR1 gene, is an important transporter for
      many drugs, xenobiotics and cytokines and may be associated with many
      immunological processes and apoptosis. The activity of P-gp is genetically
      determined. Naturally occurring MDR1 polymorphisms have been described and
      correlated with potential clinical effects. Several mutations in the MDR1 gene
      have been recognized, but only some of them are associated with P-gp expression.
      The C3435T polymorphism was found to correlate with the activity of P
      glycoprotein. The aim of the study was to evaluate the C3435T MDR1 polymorphism
      in patients with rheumatoid arthritis and to investigate a possible correlation
      with disease susceptibility, activity and severity. METHODS: The study was
      carried out in 92 patients with rheumatoid arthritis and 97 healthy subjects as a
      control group. The C3435T polymorphism was determined using the PCR-RFLP method.
      RESULTS: The distribution of C3435TT MDR1 genotypes in RA patients did not differ
      significantly from that in a control group and was as follows: 3435CC in 25
      (26.9%) subjects, 3435CT in 50 (53.8%) and 3435TT in 17 (18.3%). The probability
      of remission of RA symptoms after therapy with methotrexate and
      glucocorticosteroids however, was 2.89-fold greater in patients with the 3435TT
      genotype compared to patients with the genotypes 3435CC and 3435CT. The risk of
      having an active form of rheumatoid arthritis resistant to therapy with disease
      modifying antirheumatic drugs in patients with 3435CC and 3435CT genotypes was
      2.89 times greater than in homozygous 3435TT subjects. CONCLUSION: We suggest
      that the C3435T MDR1 polymorphism is not an important genetic risk factor for RA
      susceptibility, but that this polymorphism may have an influence on the activity
      of the disease and its response to therapy with disease-modifying antirheumatic
      drugs.

PMID- 15487809
TI  - Population pharmacokinetics of methylprednisolone in accident victims with spinal
      cord injury.
AB  - OBJECTIVE: High-dose methylprednisolone (MP) is used to treat acute spinal cord
      injury (ASCI). The objective of the present study was to determine the
      pharmacokinetics of the pro-drug methylprednisolone hemisuccinate (MPHS) and MP
      in accident victims with ASCI. METHODS: The patients (n = 26) were treated with a
      bolus intravenous loading dose of 30 mg/kg MPHS within 2 h after injury and this
      was followed by a maintenance infusion of 5.4 mg/kg/h up to 24 h. Blood, CSF and
      saliva samples were collected up to 48 h after the initial dose and the samples
      were analyzed by HPLC. Concentration-time data of MPHS and MP were analyzed using
      population pharmacokinetic analysis with NONMEM software. RESULTS: MPHS and MP
      could be monitored in plasma and CSF. MP but not MPHS was present in saliva. High
      variability was seen in the MPHS levels in CSF. The pharmacokinetics of the pro
      drug and the metabolite were adequately described by a 2-compartment model with
      exponential distribution models assigned to the interindividual and the residual
      variability. At steady state, the average measured MP concentration in plasma was
      12.3+/-7.0 microg/ml and 1.74+/-0.85 microg/ml in CSF. The CSF levels of MP could
      be modeled as a part of the peripheral compartment. CONCLUSION: This study
      demonstrated that CSF concentrations of MP were sufficiently high after i.v.
      administration and reflected the concentrations of unbound drug in plasma.
      Salivary levels of MP were about 32% of the plasma level and may serve as an
      easily accessible body fluid for drug level monitoring.

PMID- 15487810
TI  - Assessment of a multiple-dose drug interaction between ezetimibe, a novel
      selective cholesterol absorption inhibitor and gemfibrozil.
AB  - OBJECTIVE: Ezetimibe is a novel lipid-lowering drug that prevents intestinal
      absorption of dietary and biliary cholesterol leading to significant reduction in
      total-C, LDL-C, Apo B, and TG and increases in HDL-C in patients with
      hypercholesterolemia. Gemfibrozil, a fibric acid derivative, is an effective
      lipid-modulating agent that increases serum high-density lipoprotein cholesterol
      and decreases serum TG. The objective of this study was to evaluate the potential
      for a pharmacokinetic (PK) interaction between ezetimibe and gemfibrozil.
      METHODS: This was a randomized, open-label, 3-way crossover, multiple-dose study
      in 12 healthy adult male volunteers. All subjects received the following 3
      treatments orally for 7 days: ezetimibe 10 mg once daily, gemfibrozil 600 mg
      every 12 hours, and ezetimibe 10 mg once daily plus gemfibrozil 600 mg every 12
      hours. A washout period of > or = 7 days separated the 3 treatments. In each
      treatment, blood samples were collected on day 7 to assess the steady-state PK of
      ezetimibe and gemfibrozil. The oral bioavailability of ezetimibe coadministered
      with gemfibrozil relative to each drug administered alone was evaluated with an
      analysis-of-variance model. RESULTS: Ezetimibe was rapidly absorbed and
      extensively conjugated to its glucuronide metabolite. Ezetimibe did not alter the
      bioavailability (based on AUC) of gemfibrozil. The mean AUC0-12 of gemfibrozil
      was 74.7 and 74.1 microg h/ml with and without ezetimibe coadministration,
      respectively (log-transformed geometric mean ratio (GMR) = 99.2; 90% confidence
      interval (CI) = 92 - 107%). Conversely, gemfibrozil significantly (p < 0.05)
      increased the plasma concentrations of ezetimibe and total ezetimibe (i.e.
      ezetimibe plus ezetimibe-glucuronide). Exposure to ezetimibe and total ezetimibe
      was increased approximately 1.4-fold and 1.7-fold, respectively (CI = 109 - 173%
      for ezetimibe and 142 - 190% for total ezetimibe), however, this increase was not
      considered to be clinically relevant. Ezetimibe and gemfibrozil administered
      alone or concomitantly for 7 days was well tolerated. CONCLUSIONS: The
      coadministration of ezetimibe and gemfibrozil in patients is unlikely to cause a
      clinically significant drug interaction. The coadministration of these agents is
      a promising approach for patients with mixed dyslipidemia. Additional clinical
      studies are warranted.

PMID- 15487811
TI  - Bioequivalence of a prednisolone tablet administered as a single oral dose in
      healthy male volunteers.
AB  - OBJECTIVE: A bioequivalence study ofprednisolone as Nisolone (test) tablets
      versus Delta-Cortef (reference) tablets was conducted. PATIENTS AND METHODS:
      Eighteen healthy male Korean volunteers received both 20 mg formulations of
      prednisolone in this 2 x 2 crossover study with a 1-week washout period between
      the doses. Plasma concentrations of prednisolone were monitored over a period of
      12 hours after the administration using high-performance liquid chromatography.
      The AUC (area under the plasma concentration-time curve from time zero to
      infinity) and AUCt (area under the plasma concentration-time curve from time zero
      to the last sampling time) were calculated using the trapezoidal rule
      extrapolation method. The Cmax (maximum plasma drug concentration) and t(max)
      (time to reach Cmax) were compiled from the plasma concentration-time data.
      Analysis of variance was carried out using logarithmically transformed AUC, AUCt
      and Cmax and untransformed t(max). RESULTS: The geometric mean of AUCt was 1,786
      ng/ml x h (test medication) and 1,787 ng/ml xh (reference medication). A Cmax of
      409 ng/ml and 404 ng/ml was achieved for the test and the reference medication,
      respectively. Point estimates and 90% confidence intervals for AUCt (parametric)
      and Cmax (parametric) were 0.989 (0.942 approximately 1.039) and 1.013 (0.934
      approximately 1.100), respectively. These results satisfy the bioequivalence
      criteria of the European Committee for Proprietary Medicinal Products and the US
      Food and Drug Administration Guidelines. The corresponding value of t(max) was 
      0.221 (-0.415 approximately 0.000). CONCLUSION: The 2 medications of prednisolone
      examined are bioequivalent and, thus, may be prescribed interchangeably.

PMID- 15487812
TI  - The varieties of dignity.
AB  - As a part of a research project on Dignity and Older Europeans (Fifth Framework
      (Quality of Life) Programme3) I explore in this paper a set of notions of human
      dignity. The general concept of dignity is introduced and characterized as a
      position on a value scale and it is further specified through its relations to
      the notions of right, respect and self-respect. I present four kinds of dignity
      and spell out their differences: the dignity of merit, the dignity of moral or
      existential stature, the dignity of identity and the universal human dignity
      (Menschenwurde). Menschenwurde pertains to all human beings to the same extent
      and cannot be lost as long as the persons exist. The dignity of merit depends on
      social rank and position. There are many species of this kind of dignity and it
      is very unevenly distributed among human beings. The dignity of merit exists in
      degrees and it can come and go. The dignity of moral stature is the result of the
      moral deeds of the subject; likewise it can be reduced or lost through his or her
      immoral deeds. This kind of dignity is tied to the idea of a dignified character
      and of dignity as a virtue. The dignity of moral stature is a dignity of degree
      and it is also unevenly distributed. The dignity of identity is tied to the
      integrity of the subject's body and mind, and in many instances, although not
      always, also dependent on the subject's self-image. This dignity can come and go
      as a result of the deeds of fellow human beings and also as a result of changes
      in the subject's body and mind.

PMID- 15487813
TI  - Fair drug prices and the patent system.
AB  - This paper uses John Rawls' theory of justice to defend the patent system against
      charges that it has an unfair effect on access to medications,from the
      perspective of national and international justice. The paper argues that the
      patent system is fair in a national context because it respects intellectual
      property rights and it benefits the least advantaged members of society by
      providing incentives for inventors, investors, and entrepreneurs. The paper also
      argues that the patent system is fair in an international context, provided that
      developed nations take steps to help disease-stricken countries secure internal
      justice. Fairness in a national or international context also requires that the
      patent system should include emergency exceptions to deal with short-term
      inequities.

PMID- 15487814
TI  - Life extension research: health, illness, and death.
AB  - Scientists, bioethicists, and policy makers are currently engaged in a
      contentious debate about the scientific prospects and morality of efforts to
      increase human longevity. Some demographers and geneticists suggest that there is
      little reason to think that it will be possible to significantly extend the human
      lifespan. Other biodemographers and geneticists argue that there might well be
      increases in both life expectancy and lifespan. Bioethicists and policy makers
      are currently addressing many of the ethical, social, and economic issues raised
      by life extension research. However, the emphasis on philosophical argument
      supporting or condemning efforts to increase human longevity means that much less
      attention is currently being given to the factors that might play a role in
      generating interest in efforts to increase human longevity. This analysis
      considers three factors that might play a role in heightening public interest in
      efforts to develop biomedical technologies capable of retarding or reversing
      aging processes. While discussions of life extension research can seem quite
      futuristic and impractical, there are some powerful existential factors that
      might well generate considerable public support for life extension strategies if
      effective biomedical interventions emerge. Rather than providing philosophical
      justifications supporting or condemning efforts to increase human longevity, this
      essay seeks to promote a better understanding of the factors generating
      contemporary interest in prolonging life and postponing death.

PMID- 15487816
TI  - Foundation trusts and the problem of legitimacy.
AB  - The UK government is setting up a new kind of organisation as part of the
      National Health Service, the foundation trust. Foundation trusts will be more
      distanced from government than existing NHS bodies, and will have closer
      community links. In this paper I identify the importance of legitimacy in health
      care and explore the potential situation of foundation trusts in terms of the
      bases of their legitimacy as organisations. Relationships with community,
      stakeholders and government are all considered as sources of legitimacy for
      foundation hospitals, and comparisons are made with other organisations, state,
      voluntary and private. I conclude that the blueprint of the foundation hospital
      creates a set of relationships which are incoherent and mutually conflicting, and
      conceals a crucial relationship with the state. I argue that these problems are
      likely to weaken the legitimacy of the foundation trust.

PMID- 15487815
TI  - Goals in their setting: a normative analysis of goal setting in physical
      rehabilitation.
AB  - Goal setting is an important professional method and one of the key concepts that
      structure a practical field such as physical rehabilitation. However, the actual
      use of goals in rehabilitation practice is much less straightforward than the
      general acceptance of the method suggests as goals are frequently unattained,
      modified or contested. In this paper, I will argue that the difficulties of goal
      setting in day-to-day medical practice can be understood by unravelling the
      normative assumptions of goal setting, in this case three different tensions that
      come along with it. First, goals are developed for a future state that may
      require activities that clash with necessities of the present situation. Second,
      professionals in clinical rehabilitation centres elaborate goals for an
      environment that differs in terms of spatial and social characteristics from the
      environment in the centre, where people train for the accomplishment of goals.
      Finally, goal setting requires active patient participation and individual
      control that sometimes appears impossible, unrealistic, and undesirable. I will
      describe how professionals deal with these tensions in a creative and dynamic
      way. With my articulation of the assumptions of goal setting, I hope to
      contribute to the self-reflection of rehabilitation practitioners as well as to
      theoretical discussions of goal setting in contexts other than rehabilitation.

PMID- 15487817
TI  - An integrated approach to resource allocation.
AB  - Resource allocation decisions are often made on the basis of clinical and cost
      effectiveness at the expense of ethical inquiry into what is acceptable. This
      paper proposes that a more compassionate model of resource allocation would be
      achieved through integrating ethical awareness with clinical, financial and legal
      input. Where a publicly-funded healthcare system is involved, it is suggested
      that having an agency that focuses solely on cost-effectiveness leaving medical,
      legal and ethical considerations to others would help depoliticise rationing
      decisions and command greater public acceptance.

PMID- 15487818
TI  - A pox on plagues.

PMID- 15487819
TI  - A voice from private practice.

PMID- 15487820
TI  - What Islam does not need is a Pope!

PMID- 15487821
TI  - What Islam does not need is a Pope!

PMID- 15487822
TI  - What Islam does not need is a Pope!

PMID- 15487823
TI  - What Islam does not need is a Pope!

PMID- 15487824
TI  - Psychopathology and coping in recently diagnosed HIV/AIDS patients.

PMID- 15487825
TI  - Ventricular fibrillation in a clinically normal heart.

PMID- 15487826
TI  - Traditional formulary?

PMID- 15487827
TI  - Foreign doctors working in South Africa.

PMID- 15487828
TI  - The drug-addicted doctor--who dares to care?

PMID- 15487829
TI  - Hope for reducing SA's trauma deaths?

PMID- 15487830
TI  - SA has no overall health staff plan--HST.

PMID- 15487831
TI  - Small mercies for 'outfoxed' surgeons.

PMID- 15487832
TI  - Strong recommendations from global AIDS fund's first partnership forum.

PMID- 15487833
TI  - Perinatal HIV research unit clarifies nevirapine resistance and transmission
      issues.

PMID- 15487834
TI  - Phase 1 clinical data on first-in-class HIV-1 maturation inhibitor, PA-457.

PMID- 15487835
TI  - Statement on stem cell research issued by the Johns Hopkins University.

PMID- 15487836
TI  - Problems in the management of asthma in young children--a potential role for
      montelukast.

PMID- 15487837
TI  - Neurolinguisic programming in the medical consultation.

PMID- 15487838
TI  - Teleophthalmology and Vision 2020 in South Africa.

PMID- 15487839
TI  - Protean appearance and behaviour of liver hydatids.

PMID- 15487840
TI  - About Ulster without a fridge.

PMID- 15487841
TI  - South African Menopause Society Council consensus statement on menopausal hormone
      therapy.

PMID- 15487842
TI  - A survey of the use of regional anaesthesia for caesarean sections in level 1 and
      2 hospitals in the Free State.

PMID- 15487843
TI  - Forty-five years apart--confronting the legacy of racial discrimination at the
      University of Cape Town.

PMID- 15487844
TI  - Renal outcome of type 2 diabetes in South Africa--a 12-year follow-up study.
AB  - AIMS: Previous studies of type 2 diabetes mellitus have indicated a benign renal
      outcome after long-term follow-up. The aim of this study was to determine how
      often renal failure due to diabetic nephropathy was a cause of death in patients
      with type 2 diabetes. METHODS: Prospective observational study of 59 South
      African patients with type 2 diabetes over a 12-year period. During the study
      repeated clinical evaluations were accompanied by measurements of serum
      creatinine, serum cholesterol, random blood sugar, and urine protein/creatinine
      ratios. RESULTS: The mean duration of diabetes at the end of the study was 17.8
      years. There was a wide variation in the time from clinical diagnosis of diabetes
      to macroproteinuria (mean 9.7 years, SD 5.9, range 0 - 21) and the rate of
      deterioration of renal function. This rate correlated with poor control of blood
      pressure, a glucose level of > 14 mmol/l, heavy proteinuria, a high retinopathy
      score, a body mass index of < 28 and the number of pack years of smoking. At the
      end of the study 47 patients (79.7%) had died. Of these deaths 17 (28.8%) were
      due to chronic renal failure. CONCLUSIONS: In contrast to other studies we have
      shown that in a developing country renal failure in type 2 diabetic patients is a
      major cause of death. Determining the prognosis for an individual patient is
      difficult as there are wide ranges in the time of onset of proteinuria, the rise
      in serum creatinine and the time to ultimate progression to end-stage renal
      failure.

PMID- 15487845
TI  - Epidemiology of HIV in South Africa--results of a national, community-based
      survey.
AB  - OBJECTIVE: To determine HIV prevalence in the South African population and to
      investigate risk factors for HIV. METHODS: A national sample of 10 197 households
      was selected. One child (aged 2 - 14 years), one youth (15 - 24 years) and one
      adult (25 years and older) were randomly selected from each household. Consenting
      respondents were interviewed about their socio-demographic characteristics and
      asked to give an oral mucosal transudate sample to test anonymously for HIV.
      Differential response rates were compared using unweighted data. The Orasure HIV
      1 device in combination with the Vironostika HIV UNI-Form II plus O enzyme-linked
      immunosorbent assay kits were used to collect oral fluid specimens for HIV
      testing. HIV prevalence within subgroups was compared using Rao and Scott's
      adjusted chi-square. Relative risk was calculated using Poisson regression. All
      analysis was on the weighted data. RESULTS: Of the 10 197 households selected, 7
      249 (71.1%) were included in the study. Of the 13 518 individuals selected, 9 963
      (73.7%) were interviewed. Of these, 8 428 (62.3%) agreed to HIV testing and had
      valid results. HIV prevalence in the general population was 11.4% (12.8% in
      females and 9.5% in males). Blacks had the highest prevalence (12.9%), compared
      with whites (6.2%), coloureds (6.1%) and Indians (1.6%). Informal settlements in
      urban areas had the highest HIV prevalence (21.6%). The findings of this study
      are consistent with South African Department of Health estimates based on the
      2002 antenatal survey. CONCLUSION: The Nelson Mandela/Human Sciences Research
      Council survey included all race, sex and age groups. It is therefore the most
      reliable and valid source of information on the extent and distribution of the
      HIV epidemic in South Africa.

PMID- 15487846
TI  - Human immunodeficiency virus infection and child sexual abuse.

PMID- 15487847
TI  - Flow cytometry. Tumour DNA content and prognosis in squamous cell carcinoma of
      the head and neck region: a review.

PMID- 15487848
TI  - Edentulous ridge augmentation. Part II.
AB  - Edentulous ridge augmentation has evolved from an attempt to control progressive
      atrophy of both denture-bearing bone and soft tissue. Preprosthetic surgery to
      reverse these undesirable conditions should only be attempted after other
      methods, such as proper denture construction, proper patient compliance, and
      patient management have been unsuccessful. Also a thorough evaluation by both a
      prosthodontist and an oral surgeon is required. Prosthodontically, the surgical
      procedure should produce the following features: (1) enlargement of the area of
      bony support, (2) improved contour of the ridge for denture stability, and (3)
      elimination of the displacing action of muscle attachments on the complete
      denture. Ideally we would like to combine all of these distinct features to
      arrive at the goal of optimum denture retention. The oral surgeon must also be
      aware of these principles, and in essence, determines the immediate post-surgical
      results. However, the oral surgeon is also limited by specific patient factors
      such as systemic conditions, oral health maintanence, and finances. He must
      recognize these and determine which surgical methods would give the best denture
      retention and patient service. It is in this context that the prosthodontist and
      oral surgeon must work together to facilitate total patient care.

PMID- 15487849
TI  - Oral rehabilitation with overdentures: a summary of procedure and an evaluation
      of the efficacy of treatment with this type of prosthesis.

PMID- 15487850
TI  - [Cooperation between university-industry].

PMID- 15487851
TI  - [Current pharmacological principles to inhibit platelet function and their
      clinical implications. Focus on clopidogrel].
AB  - Clopidogrel is a further-developed analog of ticlopidine and currently the only
      therapeutic alternative for long-term prophylaxis and therapy of
      atherothrombosis. According to the CAPRIE trial, clopidogrel causes significantly
      less gastrointestinal bleeding than plain aspirin (ASA). There is an increased
      antiplatelet efficacy by combining clopidogrel with ASA as shown in several
      clinical trials, such as CURE and CREDO. An active metabolite of clopidogrel
      causes irreversible inhibition of the P2Y12-ADP receptor at the platelet surface,
      but does not alter the metabolism of arachidonic acid. Clopidogrel has additional
      effects on the ADP-induced expression of adhesion molecules (P-selectin,
      GPIIb/IIIa) and inflammatory mediators (CD40L). These actions, shown ex vivo,
      might be clinically relevant. Similar to ASA there can be variable antiplatelet
      activities of Clopidogrel. Their frequency can not be precisely estimated yet.
      There is neither a generally accepted definition of insufficient responsiveness
      (against inhibitors of platelet function) nor any generally accepted procedure to
      measure it, including definition of normal range.

PMID- 15487852
TI  - [Antiplatelet strategies in the acute and chronic therapy of cardiovascular
      disease].
AB  - Atherothrombotic diseases and especially coronary and cerebrovascular diseases
      are the most important causes of death in western countries. Besides the
      prevention and treatment of cardiovascular risk factors like hyperlipidemia,
      smoking and arterial hypertension along with improvements in the catheter-based
      interventional therapy, the treatment of cardiovascular diseases with platelet
      aggregation inhibitors improved the the patients' long-term outcome and
      mortality. The effect of acetylsalicylic acid (ASA) as an inhibitor of the
      cylooxygenase is well studied and proven in numerous major studies. In these
      trials, ASA improved prognosis of the patients both in acute and chronic coronary
      heart disease as well as in the primary prevention of high-risk patients. A
      similar positive and, in comparison to ASA, even stronger effect was demonstrated
      with thienopyridines as inhibitors of the ADP receptor on thrombocytes. In
      additional studies a combination of both substances showed a synergistic effect
      on platelet inhibition in the treatment of acute coronary syndromes and after
      stent implantation as interventional therapy of coronary heart disease. According
      to randomized prospective double-blind studies, a combination therapy with ASA
      and clopidogrel is indicated for patients with acute coronary syndromes and
      following coronary stent implantation for up to 12 months. A longer-lasting dual
      therapy is tested in several ongoing studies, along with the safety of this
      treatment regimen in combination with lytic therapy in acute myocardial
      infarction.

PMID- 15487853
TI  - [Antiplatelet therapy in patients with peripheral arterial disease (PAD)].
AB  - Peripheral arterial disease (PAD) is not an uncommon but a commonly neglected
      condition by many medical practitioners. Its prevalence steadily increases with
      age. In Germany almost one fifth of the patients aged > 65 years suffer from it.
      With increasing life expectancy the prevalence of PAD seems to be on the
      increase. PAD is a manifestation of diffuse and severe atherosclerosis. A very
      strong association exists between PAD and other atherosclerotic disorders such as
      coronary artery disease (CAD) and cerebrovascular disease (CVD). PAD is an
      independent predictor of high mortality in patients with CAD. Smoking, diabetes
      mellitus and advancing age are the cardinal risk factors. A relatively small
      number of PAD patients lose limbs by amputation. Most patients with PAD die of
      either heart attacks or strokes and they die of the former conditions far earlier
      than controls. Numerous authors have reported activation of the coagulatory
      system in PAD, possibly because of the diffuse pattern of the disease. Platelet
      hyperactivity in PAD may play a role in the process that leads to complications
      and disease progression. Thus, antiplatelet treatment in these patients may be
      essential to reduce their high mortality rate. Antiplatelet therapy for
      prevention of secondary vascular events is the cornerstone of pharmacological
      intervention in PAD. Based on current evidence, treating patients with PAD with
      antiplatelet drugs appears to be effective in reducing the risk of coronary and
      cerebrovascular events, in maintaining arterial and graft patency, and in slowing
      progression of disease. On the other hand, several studies indicated, that
      platelets in patients with PAD are relatively aspirin-resistant. The data from
      the CAPRIE Trial suggest a clinically and statistically significant better risk
      reduction with clopidogrel than with aspirin in patients with PAD. Aspirin alone
      should no longer be considered the optimal therapy for PAD.

PMID- 15487854
TI  - [Secondary prevention of stroke with antiplatelet drugs].
AB  - Patients suffering from a transient ischemic attack (TIA) or ischemic stroke are
      at high risk of a recurrent stroke. The risk is between 10% and 15% in the 1st
      year after the event and highest in the immediate period following the index
      event. In patients without cardiac source of embolism, the risk of stroke can be
      reduced by acetylsalicylic acid (ASA). The relative risk reduction for recurrent
      vascular events (myocardial infarction, stroke, vascular death) with aspirin is
      18% and the risk reduction for stroke 13%. Clopidogrel is superior to ASA in
      patients with high risk of recurrence due to concomitant vascular disease or
      multiple risk factors. Clinical trials for secondary stroke prevention at present
      focus on combination antiplatelet therapy. Large clinical trials such as MATCH,
      CARESS, CHARISMA, and PRoFESS will investigate whether combination antiplatelet
      therapy is superior to monotherapy and whether the combination of dipyridamole
      plus ASA is comparable to clopidogrel plus ASA in terms of efficacy and safety.

PMID- 15487855
TI  - [Renovascular hypertension/renal artery stenosis. Chief symptoms: arterial
      hypertension].

PMID- 15487856
TI  - [Radiotherapy of rectal cancer].
AB  - The hallmark of successful management of rectal cancer is complete resection. In
      early stage disease, removal of all of the perirectal soft tissue structures, the
      mesorectum can be achieved with a total mesorectal excision (TME), resulting in
      high rates of local control. In cases of cancer extending through the muscularis
      propria or in case of lymphonodal involvement, additional radiation therapy can
      further substantially reduce the risk of pelvic recurrences. The combined
      treatment with radiotherapy followed by surgery is more effective than
      postoperative radiotherapy. Preoperative radiotherapy increases the survival rate
      of rectal cancer patients using limited doses of ionizing radiation and
      customized treatment volumes. The introduction of functional imaging with
      positron-emission tomography integrated in a conventional computer-associated
      tomography system (PET/CT) can be used for radiation treatment planning enhancing
      treatment precision and standards. The PET/imaging can be reliably used therapy
      for the purpose of combined staging and treatment volume assessment.

PMID- 15487857
TI  - [Antihypertensive effectiveness of angiotensin II receptor antagonists].

PMID- 15487858
TI  - [Laparoscopy resection for colon cancer. The new standard?].
AB  - Surgical resection is the primary treatment for colon cancer. The introduction
      and acceptance of laparoscopic colectomy for cancer has been gradual for a number
      of reasons including the fact that it is technically challenging, has less than
      dramatic patient benefits, and perhaps most significantly it could theoretically
      represent a compromise as an oncologic procedure. Evidence suggests that
      laparoscopic colectomy for colon cancer is safe, feasible, and an oncologic
      adequate resection can be performed with acceptable operative times and
      conversion rates. It may result in improved outcomes when performed by
      experienced surgeons. The recently published results from the largest and first
      prospective randomized trial with sufficient statistical power have shown that
      laparoscopic colectomy is as effective as open colectomy in preventing recurrence
      and death from colon cancer. In experienced hands, laparoscopic colectomy for the
      cure of colorectal cancer appears to be equivalent to open surgery and may become
      standard in selected patients.

PMID- 15487859
TI  - [Weekly Fosamax tablet is significantly more effective than risedronate daily, as
      results of the Head-to-Head Study show].

PMID- 15487860
TI  - [New drugs for colorectal cancer].
AB  - Drug treatment of colorectal cancer has made impressive progress during the past
      10 years. In addition to fluorouracil new anticancer drugs like irinotecan and
      oxaliplatin have become available. The activity of fluorouracil was optimized by
      using schedules of prolonged infusion. Capecitabine is an oral pro-drug of
      fluorouracil. When colorectal metastases are limited to the liver they should be
      resected if possible. Sometimes they can be reduced in size by primary
      chemotherapy (downstaging) and resected later. Very new and exciting are reports
      with the monoclonal antibody bevacizumab in combination with chemotherapy.
      Bevacizumab blocks angiogenesis. So far it is available only in the USA.

PMID- 15487861
TI  - [Sore throat and rapid pulse. Patient: female, 25 years old].

PMID- 15487862
TI  - [Balsam for the liver].

PMID- 15487863
TI  - A missed opportunity.

PMID- 15487865
TI  - More than a makeover.

PMID- 15487864
TI  - Nowhere to call home.

PMID- 15487866
TI  - Good tidings we bring.

PMID- 15487867
TI  - A force at work.

PMID- 15487868
TI  - Star performance.

PMID- 15487869
TI  - Speak up for life.

PMID- 15487870
TI  - Lessons in death.

PMID- 15487871
TI  - Narratives of therapeutic touch.
AB  - This article aims to increase the understanding of therapeutic touch (TT) and its
      role in supporting patients with cancer through the different stages of illness.
      The article includes a number of narratives, collected during an audit and
      written by patients, to illustrate the use of TT in helping them to cope with the
      emotional experiences associated with diagnosis and subsequent treatment.

PMID- 15487872
TI  - Wound management in palliative care.
AB  - This article explores the challenges nurses face when caring for patients with
      wounds in a palliative care context. Combining the principles of effective wound
      management with the key elements of holistic, person-centred care will ensure
      that realistic and patient-focused aims of management are identified. Nurses with
      effective communication skills can play an important role in supporting patients
      and their families at a difficult time.

PMID- 15487873
TI  - Leg ulceration part 1: aetiology and pathophysiology.
AB  - In part one of this article, the underlying causes of chronic leg ulcers,
      professional issues and the anatomy and physiology of the lower limb are
      examined.

PMID- 15487874
TI  - CDC rolls out nerve-agent antidote program.

PMID- 15487875
TI  - Proposed rule discusses Medicare medication management services.

PMID- 15487876
TI  - Dispensing investigational drugs: regulatory issues and the role of the
      investigational drug service.

PMID- 15487877
TI  - Journal club 101 for the new practitioner: evaluation of a clinical trial.

PMID- 15487878
TI  - Integrity of the pharmaceutical supply chain: product sourcing for patient
      safety.

PMID- 15487879
TI  - Management of pressure ulcers.
AB  - PURPOSE: Wound healing, the epidemiology and staging of pressure ulcers, and
      pressure ulcer prevention and treatment are discussed. SUMMARY: The principal
      event leading to the formation of pressure ulcers appears to be a consistent
      interruption in blood supply to the skin. Several known risk factors exist and
      can be attributed to patient-specific variables and wound-specific conditions.
      Initial management should include removal of the source of pressure, a
      comprehensive assessment of the patient, and proper staging of the ulcer.
      Preparation of the wound for treatment is essential and can have a significant
      impact on healing. While the patient's nutritional status is thought to affect
      wound healing, only an increased protein content in the diet has been
      demonstrated to have a benefit. Specialized wound dressings are available for
      pressure ulcers of all stages and drainage characteristics. With wide variation
      in cost and in application regimens, a direct cost-effectiveness comparison of
      commercially available dressing products is difficult. Many of the growth factors
      commonly present in healing wounds have been synthesized and evaluated as
      treatments. Although topical platelet-derived growth factor has demonstrated
      benefit in some studies, its use remains controversial. To date, no topical
      growth factors carry FDA-approved labeling for use in the treatment of pressure
      ulcers. Human skin equivalents mark the latest advancement in therapy. Certain
      species of bacteria have been associated with poorly healing ulcers and may
      warrant intervention with either local or systemic antibiotic therapy.
      CONCLUSION: No pharmacologic intervention has been conclusively shown to be
      effective for pressure ulcers. The cornerstones of therapy remain elimination of
      the source of pressure or friction and appropriate wound care. usa.

PMID- 15487880
TI  - Nature and causes of clinically significant medication errors in a tertiary care
      hospital.
AB  - PURPOSE: Medication errors identified through solicited error reports in general
      medicine and specialty units of a major tertiary care teaching hospital were
      studied to identify prevalent patterns and causes. METHODS: Medication error
      reports by a multidisciplinary team of eight clinicians at adult medical and
      surgical, hematology and oncology, bone marrow transplantation, and medical and
      cardiac intensive care units were collected prospectively over a three-month
      period. The reports were validated in terms of clinical significance, causality,
      and true presence of an error by two independent reviewers. Cluster analysis of
      valid reports (reports accepted by both reviewers) was used to identify prominent
      error patterns. RESULTS: Of 321 medication error reports, 240 were included in
      the analysis. Of these, 95 represented manifested errors and the rest near misses
      (not manifested [94] or averted [51]). Most manifested errors involved
      uncontrolled infections associated with prescribed underdoses of antiinfectives
      (23%), renal failure associated with prescribed overdoses of antiinfectives (4%),
      central-nervous-system drug intoxication following prescribed overdoses (4%), or
      uncontrolled pain associated with prescribed underdoses (4%). Most errors were
      initiated during prescribing (72%) and were associated with deficits in
      pharmacotherapy knowledge (39%) or with failure to consider critical patient
      information (18%). Errors initiated during dispensing and administration were
      mostly associated with performance deficits (e.g., accidental slips and lapses).
      CONCLUSION: A limited number of prevalent medication-error patterns described
      more than half of all reported errors in a hospital and suggested excellent areas
      for quality improvement. Error causes varied with the node of the medication-use
      process where they arose and suggested the need for tailored interventions to
      improve clinicians' performance.

PMID- 15487881
TI  - Risk assessment of NSAID-induced gastrointestinal toxicity in ambulatory care
      patients.
AB  - PURPOSE: The risk of gastrointestinal (GI) toxicity associated with the use of a
      traditional nonsteroidal antiinflammatory drug (NSAID) versus a cyclooxygenase-2
      (COX-2) inhibitor was compared among patients in a managed care organization.
      METHODS: Patients over 18 years old who received a prescription for ibuprofen,
      naproxen, celecoxib, or rofecoxib between March 2001 and June 2001 were included
      in this study. All subjects were followed for 12 months for GI complications,
      medication use, and changes in physical conditions from baseline. A simplified
      risk-scoring scale was used to measure patients' risk of GI complications.
      RESULTS: A total of 172 patients were randomly selected: 86 receiving traditional
      NSAIDs and 86 receiving COX-2 inhibitors. Patients receiving COX-2 inhibitors
      were older and more likely to be receiving treatment for osteoarthritis (OA) or
      rheumatoid arthritis (RA), while patients taking traditional NSAIDs were more
      likely to be receiving treatment for acute pain. The average risk scores for
      patients receiving traditional NSAIDs and COX-2 inhibitors were 0.23% and 0.36%,
      respectively (p = 0.11). When stratified by indication, there was a significant
      difference in the risk score for acute pain (p = 0.02) but not for OA, RA, or
      chronic pain. No GI adverse effects occurred in either group. CONCLUSION: Among
      patients in a managed care organization who were taking NSAIDs, most were at low
      risk for an NSAID-related GI adverse effect. The risk of GI adverse effects did
      not differ significantly between patients treated with a traditional NSAID and
      those treated with a COX-2 inhibitor.

PMID- 15487882
TI  - Establishing an alteplase dosing protocol for hemodialysis-catheter thrombosis.

PMID- 15487883
TI  - Compatibility and stability of ceftazidime sodium and tenoxicam in 5% dextrose
      injection.

PMID- 15487884
TI  - USP chapter 797: establishing a practice standard for compounding sterile
      preparations in pharmacy.

PMID- 15487885
TI  - Metabolic complications of parenteral nutrition in adults, part 1.
AB  - PURPOSE: Common metabolic complications associated with parenteral nutrition (PN)
      are reviewed, and the consequences of overfeeding and variables for patient
      monitoring are discussed. SUMMARY: Although PN is a lifesaving therapy in
      patients with gastrointestinal failure, its use may be associated with metabolic,
      infectious, and technical complications. The metabolic complications associated
      with PN in adult patients include hyperglycemia, hypoglycemia, hyperlipidemia,
      hypercapnia, refeeding syndrome, acid-base disturbances, liver complications,
      manganese toxicity, and metabolic bone disease. These complications may occur in
      the acute care or chronic care patient. The frequency and severity of these
      complications depend on patient- and PN-specific factors. Proper assessment of
      the patient's nutritional status; tailoring the macronutrient, micronutrient,
      fluid, and electrolyte requirements on the basis of the patient's underlying
      diseases, clinical status, and drug therapy; and monitoring the patient's
      tolerance of and response to nutritional support are essential in avoiding these
      complications. Early recognition of the signs and symptoms of complications and
      knowledge of the available pharmacologic and nonpharmacologic therapies are
      essential to proper management. PN should be used for the shortest period
      possible, and oral or enteral feeding should be initiated as soon as is
      clinically feasible. The gastrointestinal route remains the most physiologically
      appropriate and cost-effective way of providing nutritional support. CONCLUSION:
      PN can lead to serious complications, many of which are associated with
      overfeeding. Close management is necessary to recognize and manage these
      complications.

PMID- 15487886
TI  - ASHP Therapeutic Position Statement on the Use of Low-Molecular-Weight Heparins
      for Adult Outpatient Treatment of Acute Deep-Vein Thrombosis.
AB  - Outpatient treatment of DVT with LMWHs offers the opportunity to dramatically
      reduce the cost of treating DVT and improve the quality of life without
      compromising clinical outcomes. Given the choice, most patients are willing to be
      treated at home and are comfortable with or willing to accept the idea of giving
      themselves injections of LMWHs. Establishing comprehensive outpatient treatment
      guidelines is important to ensure that adequate support is provided by the
      anticoagulation provider. Pharmacists have assumed lead roles in developing and
      maintaining successful outpatient DVT treatment programs. Because of the safety,
      effectiveness, and potential savings associated with treating patients with acute
      DVT in the outpatient setting, ASHP encourages health care professionals to
      become or remain actively involved in the development and documentation of
      innovative outpatient DVT treatment programs. These programs will also facilitate
      the use of newer antithrombotic agents as they become available and receive
      approval for outpatient DVT treatment.

PMID- 15487887
TI  - Education and training of pharmacy students.

PMID- 15487888
TI  - SCP-1 cancer/testis antigen is a prognostic indicator and a candidate target for
      immunotherapy in epithelial ovarian cancer.
AB  - SCP-1 is a novel tumor antigen that belongs to the growing family of
      cancer/testis (CT) antigens, and it is a potential target for immunotherapy. In
      an effort to determine the expression of SCP-1 in epithelial ovarian cancer
      (EOC), one-step RT-PCR was performed with RNA from epithelial ovarian tumor
      tissues and with two normal ovarian surface epithelial cell lines. We used
      immunohistochemistry (IHC) to investigate SCP-1 expression in paraffin-fixed EOC
      samples and ELISA to test sera from a subgroup of patients for SCP-1 antibody.
      SCP-1 was expressed in 15 out of 100 (15%) primary tumors, as determined by RT
      PCR. The normal ovarian surface epithelial cell lines were negative for SCP-1
      expression, as were a panel of other normal tissues. None of the patients whose
      tumors were determined to be SCP-1 positive by RT-PCR expressed the antigen by
      IHC or demonstrated a humoral immune response by ELISA. Tumors that expressed SCP
      1 mRNA tended to have a higher grade than those that did not (P = 0.03). There
      was a significant decrease in survival time (P = 0.004) for patients with SCP-1
      mRNA-positive tumors compared to those with SCP-1 mRNA-negative tumors [median 25
      mo, 95% confidence interval (CI) 0-56 mo; and median 97 mo, CI 32-162 mo,
      respectively]. The present study shows that SCP-1 mRNA expression in patients
      with EOC is associated with a poorer chance of survival. These findings imply
      that further evaluation of SCP-1 as a potential target for vaccine therapy in EOC
      is warranted.

PMID- 15487889
TI  - D-penicillamine-induced autoimmunity in the Brown Norway rat: role for both T and
      non-T splenocytes in adoptive transfer of tolerance.
AB  - The D-penicillamine autoimmune syndrome observed in Brown Norway (BN) rats is
      similar to an idiosyncratic reaction seen in some patients. We have previously
      shown that 2 weeks of low dose (5 mg/day) D-penicillamine pretreatment completely
      prevented all clinical signs of autoimmunity normally observed in 60-80% of rats
      treated with high dose (20 mg/day) D-penicillamine. We demonstrated that this
      tolerance is immune-mediated; tolerance to D-penicillamine is long lasting, we
      can adoptively transfer splenocytes from tolerant rats into slightly irradiated
      naive syngeneic recipients, and rats exposed to low dose D-penicillamine produce
      tolerogenic cytokines [Masson, M. J., and Uetrecht, J. P. (2004) Tolerance
      induced by low dose D-penicillamine in the brown norway rat model of drug-induced
      autoimmunity is immune-mediated. Chem. Res. Toxicol. 17, 82-94]. The aim of this
      study was to provide further understanding of the cells that are responsible for
      transferring tolerance and to assess the presence of regulatory T cells in the
      spleen of tolerant animals. We cotransferred T cells or splenocytes depleted of T
      cells from tolerant BN rats with splenocytes from naive BN rats into lightly
      irradiated syngeneic recipients. We found that neither tolerant splenocyte
      subpopulation could completely prevent clinical signs of autoimmunity. These
      results demonstrate that immune tolerance to D-penicillamine-induced autoimmunity
      may require both antigen presenting cells and T cells.

PMID- 15487890
TI  - Macrophage-mediated endothelial inflammatory responses to airborne particulates:
      impact of particulate physicochemical properties.
AB  - Epidemiological studies have implicated a role for airborne particulates of <2.5
      microm diameter in the development/exacerbation of chronic cardiopulmonary
      disease; however, specific pathogenic mechanisms and the etiological significance
      of particle physicochemical properties remain unresolved. Using a microporous
      aluminosilicate zeolite Y as a manifold, we have synthesized 1 microm
      particulates of pure carbon (C), carbon-iron (C/Fe), and carbon-iron/fluoro
      aluminum silicate (C-Fe/F-Al-Si). We have used these particulates, as well as
      coal fly ash (CFA) and diesel exhaust particulates (DEP), to test the hypotheses
      that human macrophages treated with particulates elaborate proinflammatory
      cytokines in quantities sufficient to induce endothelial adhesion molecule
      expression and that macrophage responses to particulate exposure vary as a
      function of particulate physicochemical properties. Human monocyte-derived
      macrophages (Mo) were exposed for 24 h to sublethal concentrations of
      particulates, at which time phagocytosis was evident from optical microscopy.
      Human arterial, microvascular, or venous endothelial cells (EC) were treated with
      clarified supernatants recovered from Mo cultures, stained with fluorescein
      conjugated mononclonal antibodies specific for endothelial adhesion molecules
      intercellular adhesion molecule-1, vascular cell adhesion molecule-1, or E
      selectin, and assayed by fluorescence flow cytometry. Data generated by these
      experiments demonstrate that while supernatants of Mo exposed to CFA and C
      particulates are relatively ineffective, supernatants from DEP, C/Fe, or C-Fe/F
      Al-Si strongly induced adhesion molecule expression on EC, responses which were
      completely attenuated by antibody with blocking specificity for tumor necrosis
      factor alpha. Because the only difference between C and C/Fe particulates is the
      presence of surface iron on C/Fe, these findings suggest particulate-induced
      oxidative stress as a contributing factor in Mo activation and implicate redox
      active iron as a major determinant of particulate bioreactivity.

PMID- 15487891
TI  - Induction of reversible cysteine-targeted protein oxidation by an endogenous
      electrophile 15-deoxy-delta12,14-prostaglandin J2.
AB  - We have previously shown that a prostaglandin D(2) metabolite, 15-deoxy
      delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), is the potent inducer of
      intracellular oxidative stress on human neuroblastoma SH-SY5Y cells [Kondo, M.,
      Oya-Ito, T., Kumagai, T., Osawa, T., and Uchida, K. (2001) Cyclopentenone
      prostaglandins as potential inducers of intracellular oxidative stress. J. Biol.
      Chem. 276, 12076-12083.]. In the present study, to investigate the correlation
      between the redox regulation and the 15d-PGJ(2)-induced oxidative stress and to
      establish the cellular mechanism for protection against the endogenous
      electrophile, we analyzed S-oxidized proteins using biotinylated cysteine as a
      molecular probe. In addition, the reversible regulation of protein function by S
      oxidation/thiolation was characterized in vitro. When human neuroblastoma SH-SY5Y
      cells were exposed to 15d-PGJ(2), followed by treatment with biotinylated
      cysteine, 26 proteins, including glycolytic enzymes, cytoskeletal proteins, redox
      enzymes, and stress proteins, were identified as substrates for reversible
      cysteine-targeted oxidation. To investigate the regulatory mechanism of protein
      function by S-oxidation/thiolation, the binding of a low molecular weight thiol
      (glutathione) to a glycolytic enzyme alpha-enolase was characterized. Treatment
      of alpha-enolase with the thiol oxidant diamide in the presence of glutathione in
      vitro resulted in the binding of glutathione to the protein and concomitant loss
      of the enzymatic activity, whereas the glutathiolation and inactivation of alpha
      enolase were fully reversed by dithiothreitol. Mass spectrometric analysis of the
      tryptic fragments from native and oxidized alpha-enolase identified two cysteine
      residues, Cys-118 and Cys-388, as the S-oxidation sites, which may play a role in
      the regulation of the biological activities of the protein and may be regulated
      by a reversible S-oxidation/thiolation reaction. These results suggest that
      cysteine-targeted oxidation/thiolation plays a critical role in the regulation of
      protein function under conditions of electrophile-induced oxidative stress.

PMID- 15487892
TI  - Thiyl radical reaction with amino acid side chains: rate constants for hydrogen
      transfer and relevance for posttranslational protein modification.
AB  - Thiyl radicals are prominent intermediates during biological conditions of
      oxidative stress and have been suggested to be involved in the mutagenic effects
      of thiols. While several enzymatic processes rely on the formation and selective
      reactions of protein thiyl radicals with substrates, such reactions may represent
      a source for biological damage when occurring uncontrolled during oxidative
      stress. For example, intramolecular hydrogen transfer reactions to protein
      cysteine thiyl radicals may lead to secondary amino acid oxidation products,
      which may represent starting points for protein aggregation and/or fragmentation.
      Here, we have used a kinetic NMR method to determine rate constants, k(sc), for
      hydrogen transfer reactions between thiyl radicals and amino acid side chain C-H
      bonds at 37 degrees C. Rate constants cover a range between k(sc) <or= 1 x 10(3)
      M(-1) s(-1) (Val) and k(sc) = 1.6 x 10(5) M(-1) s(-1) (Ser). On the basis of
      these values and earlier data, model calculations are performed, which will
      demonstrate that protein thiyl radicals may attack protein C-H bonds via
      intramolecular hydrogen transfer at physiological conditions, potentially
      resulting in irreversible protein damage.

PMID- 15487893
TI  - Acid-induced structural modifications of unsaturated Fatty acids and phenolic
      olive oil constituents by nitrite ions: a chemical assessment.
AB  - The structural modifications of the unsaturated fatty acid components of
      triglycerides in extra virgin olive oil (EVOO) following exposure to nitrite ions
      in acidic media were determined by two-dimensional (2D) NMR spectroscopy, aided
      by (15)N labeling and GC analysis, allowing investigation of the matrix without
      fractionation steps. In the presence of excess nitrite ions in a 1% sulfuric
      acid/oil biphasic system, extensive double bond isomerization of the
      oleic/linoleic acid components of triglycerides was observed associated with
      nitration/oxidation processes. Structurally modified species were identified as
      E/Z-nitroalkene, 1,2-nitrohydroxy, and 3-nitro-1-alkene(1,5-diene) derivatives
      based on (1)H, (13)C, and (15)N 2D NMR analysis in comparison with model
      compounds. Minor constituents of EVOO, including phenolic compounds and
      tocopherols, were also substantially modified by nitrite-derived nitrating
      species, even under milder reaction conditions relevant to those occurring in the
      gastric compartments. Novel nitrated derivatives of tyrosol, hydroxytyrosol, and
      oleuropein (6-8) were identified by LC/MS analysis of the polar fraction of EVOO
      and by comparison with synthetic samples. Overall, these results provide the
      first systematic description at the chemical level of the consequences of
      exposing EVOO to nitrite ions at acidic pH and offer an improved basis for
      further investigations in the field of toxic nitrosation/nitration reactions and
      dietary antinitrosating agents.

PMID- 15487894
TI  - Effects of Azaspiracids 2 and 3 on intracellular cAMP, [Ca2+], and pH.
AB  - Azaspiracids (AZs) are a new group of phycotoxins discovered in the Ireland coast
      that includes the isolated analogues: AZ-1, AZ-2, AZ-3, AZ-4, and AZ-5 and the
      recently described AZ-6-11. Toxic episodes of AZs show gastrointestinal illness
      as in diarrhetic shellfish poisoning, but neurotoxic symptoms are also observed
      in a mouse bioassay. Despite their great importance in human health, so far, its
      mechanism of action is largely unknown. In this report, we present the first data
      of AZ-2 and AZ-3 effects on intracellular cyclic adenosine monophosphate (cAMP),
      intracellular calcium ([Ca(2+)](i)), and cytosolic pH levels (pH(i)) in freshly
      human lymphocytes. The variations of cAMP, calcium, and pH were determined by
      fluorescence digital imaging microscopy using recombinant fluorescein- and
      rhodamine-labeled protein kinase A, Fura2-AM, and 2',7'-bis(carboxyethyl)-5(6)
      carboxyfluorescein acetoxymethyl ester, respectively. Our experiments show that
      both analogues, AZ-2 and AZ-3, clearly increase cytosolic cAMP levels of human
      lymphocytes. In calcium studies, we found that only if cells are initially in a
      calcium-free medium, AZ-2 increases the intracellular calcium concentration with
      two components: Ca(2+) release from internal stores and Ca(2+) influx from
      extracellular medium. AZ-2 sensitive Ca(2+) stores seem to be different from the
      thapsigargin sensitive one. AZ-2-induced Ca(2+) influx is mediated through Ni(2+)
      and SKF96365 blockable channels, and it is additive with Tg-induced Ca(2+)
      influx. Surprisingly, AZ-3 does not empty intracellular stores but also increases
      cytosolic calcium levels. This AZ-3-induced Ca(2+) influx is mediated through
      Ni(2+) blockable channels, and it is not additive with Tg-induced Ca(2+) influx.
      In addition, AZ-3 slightly alkalinizes cytosol. In accordance with cAMP studies,
      we found that adenylyl cyclase (AC) modulation inhibits AZ-2- and AZ-3-evoked
      Ca(2+) increase and AZ-3-induced pH(i) rise. Thus, both analogues seem to involve
      an AC pathway, although its effects on [Ca(2+)](i) and pH(i) are quite different.

PMID- 15487895
TI  - Prooxidant activity and cytotoxic effects of indole-3-acetic acid derivative
      radicals.
AB  - Previously, it was shown that indole-3-acetic acid (IAA) is a nontoxic prodrug
      that forms a radical, toxic to tumor cells when activated by peroxidase. Because
      of this, IAA and peroxidase conjugated to an antibody specific to an extracelluar
      tumor antigen are currently in phase II clinical trials. In the following, the
      prooxidant activities of the radicals formed were compared when IAA or its
      derivatives were metabolically oxidized by peroxidase/H(2)O(2). In general, it
      was found that the effectiveness of IAA analogues for catalyzing the cooxidation
      of ascorbate, NADH, or GSH increased as the IAA derivatives were more readily
      oxidized by HRP/H(2)O(2). The order of effectiveness of IAA derivatives at
      cooxidizing NADH, ascorbate, GSH, and hepatocyte GSH was 5MeO-2Me-IAA > 2Me-IAA >
      5MeO-IAA > IAA. The rates of NADH and ascorbate cooxidation were faster at pH 7.4
      than at pH 6.0, whereas GSH cooxidation was faster at pH 6.0 than at pH 7.4.
      Furthermore, NADH, ascorbate, and GSH prevented the oxidation of IAA derivatives,
      which suggested that the indolyl cation radical was responsible for the
      prooxidant activity. The effectiveness of IAA derivatives in catalyzing lipid
      peroxidation at pH 7.4 was similar and also correlated with the rate of oxidation
      of IAA derivatives by HRP-I and the one-electron potential of these compounds.
      The IAA derivative-induced lipid peroxidation was faster at pH 6.0 than at pH
      7.4. IAA derivative effectiveness at catalyzing microsomal and hepatocyte lipid
      peroxidation or hepatocyte reactive oxygen species formation at pH 6.0 was IAA >
      5MeO-2Me-IAA > 2Me-IAA > 5MeO-IAA, but at pH 7.4, it was 5MeO-2Me-IAA > 2Me-IAA >
      5MeO-IAA > IAA. Previously, the rate of radical cation decarboxylation to skatole
      radicals and (skatole) peroxyl radicals was reported to be faster at an acid pH
      with IAA being more effective than the derivatives. This suggests that IAA
      skatole and/or (skatole) peroxyl radicals catalyze lipid peroxidation at pH 6.0.
      Incubation of isolated rat hepatocytes with IAA analogues/H(2)O(2)/peroxidase
      also resulted in cytotoxicity with 5MeO-2Me-IAA being the most effective at pH
      7.4 and IAA being the most effective at pH 6.0. Cytotoxicity was also prevented
      by antioxidants.

PMID- 15487896
TI  - Detection of covalent adducts to cytochrome P450 3A4 using liquid chromatography
      mass spectrometry.
AB  - Protein covalent labeling can be an undesirable property of compounds being
      studied in drug discovery programs. Identifying such compounds relies on the use
      of radiolabeled material, which requires an investment in time and resources not
      typically expended until later in the discovery process. We describe the
      detection of covalent adducts to cytochrome P450 3A4, the most abundant and
      important P450 from a human and drug discovery viewpoint, using liquid
      chromatography mass spectrometry. The technique is illustrated using L-754,394
      and 6',7'-dihydroxybergamottin, two known inhibitors of P450 3A4. Mass
      spectrometry of the intact apoprotein as well as the adducted protein is
      demonstrated. Such methodology may provide the means for screening compounds for
      covalent protein binding without the use of a radiolabel. It also provides direct
      information about mechanism-based inhibitors in terms of extent, stoichiometry,
      and nature of the adduct(s) (mass shift). This information may provide a means
      for understanding the mechanism of covalent labeling earlier in a drug discovery
      environment.

PMID- 15487897
TI  - Lead chromate-induced chromosome damage requires extracellular dissolution to
      liberate chromium ions but does not require particle internalization or
      intracellular dissolution.
AB  - Hexavalent chromium [Cr(VI)] is a well-established human lung carcinogen. Water
      solubility has proven to be a key factor in the carcinogenicity of Cr(VI), with
      the water insoluble or "particulate" compounds the more potent carcinogens.
      Pathology studies indicate that chromates target cells at bronchial bifurcation
      sites in human lungs. However, it is uncertain what roles particle
      internalization and dissolution play in the genotoxicity of these compounds to
      human lung cells. We investigated these mechanisms in a human lung cell line
      after exposure to particulate lead chromate. We found that lead chromate was
      clastogenic in a concentration-dependent manner with 0.1, 0.5, and 1
      microg/cm(2), while 5 and 10 microg/cm(2) caused complete cell cycle arrest. We
      also found concentration-dependent increases in intracellular and extracellular
      chromium ion levels. We investigated particle internalization by using
      transmission electron microscopy and found an apparent relative increase with
      concentration but no apparent particle internalization at the lowest
      concentration (0.1 microg/cm(2)) even after 24 h. Furthermore, we found no
      lysosomal association with the vacuoles containing particles, further suggesting
      that intracellular dissolution did not occur. Cotreating the cells with lead
      chromate and vitamin C eliminated both the uptake of ionic chromium and the
      clastogenic activity of lead chromate but had no effect on particle
      internalization. These data indicate that in human bronchial cells lead chromate
      clastogenesis is mediated by the extracellular dissolution of the particles and
      not their internalization. These findings have important implications for our
      understanding of the physicochemical mechanism of particulate chromates as they
      contradict previous indirect data from human bronchial epithelial cells, which
      suggest that particles dissolve inside those cells. Thus, these new data suggest
      that there may be different mechanisms of genotoxicity for epithelial cells and
      fibroblasts exposed to chromate particles.

PMID- 15487898
TI  - Contribution of aldehyde oxidase, xanthine oxidase, and aldehyde dehydrogenase on
      the oxidation of aromatic aldehydes.
AB  - Aliphatic aldehydes have a high affinity toward aldehyde dehydrogenase activity
      but are relatively poor substrates of aldehyde oxidase and xanthine oxidase. In
      addition, the oxidation of xenobiotic-derived aromatic aldehydes by the latter
      enzymes has not been studied to any great extent. The present investigation
      compares the relative contribution of aldehyde dehydrogenase, aldehyde oxidase,
      and xanthine oxidase activities in the oxidation of substituted benzaldehydes in
      separate preparations. The incubation of vanillin, isovanillin, and
      protocatechuic aldehyde with either guinea pig liver aldehyde oxidase, bovine
      milk xanthine oxidase, or guinea pig liver aldehyde dehydrogenase demonstrated
      that the three aldehyde oxidizing enzymes had a complementary substrate
      specificity. Incubations were also performed with specific inhibitors of each
      enzyme (isovanillin for aldehyde oxidase, allopurinol for xanthine oxidase, and
      disulfiram for aldehyde dehydrogenase) to determine the relative contribution of
      each enzyme in the oxidation of these aldehydes. Under these conditions, vanillin
      was rapidly oxidized by aldehyde oxidase, isovanillin was predominantly
      metabolized by aldehyde dehydrogenase activity, and protocatechuic aldehyde was
      slowly oxidized, possibly by all three enzymes. Thus, aldehyde oxidase activity
      may be a significant factor in the oxidation of aromatic aldehydes generated from
      amines and alkyl benzenes during drug metabolism. In addition, this enzyme may
      also have a role in the catabolism of biogenic amines such as dopamine and
      noradrenaline where 3-methoxyphenylacetic acids are major metabolites.

PMID- 15487899
TI  - Homolytic pathways drive peroxynitrite-dependent Trolox C oxidation.
AB  - Peroxynitrite is a powerful oxidant implicated as a mediator in nitric oxide
      ((*)NO)- and superoxide (O(2)(*)(-))-dependent toxicity. Peroxynitrite homolyzes
      after (i) protonation, yielding hydroxyl ((*)OH) and nitrogen dioxide ((*)NO(2))
      free radicals, and (ii) reaction with carbon dioxide (CO(2)), yielding carbonate
      radical anion (CO(3)(*)(-)) and (*)NO(2). Additionally, peroxynitrite reacts
      directly with several biomolecules. It is currently accepted that alpha
      tocopherol is one important antioxidant in lipid compartments and its reactions
      with peroxynitrite or peroxynitrite-derived radicals may be relevant in vivo.
      Previous reports on the peroxynitrite reaction with Trolox C (TxOH)--an alpha
      tocopherol water soluble analogue--suggested a direct and fast reaction. This was
      unexpected to us as judged from the known reactivities of peroxynitrite with
      other phenolic compounds; thus, we thoroughly investigated the kinetics and
      mechanism of the reaction of peroxynitrite with TxOH and its modulation by CO(2).
      Direct electron paramagnetic resonance studies revealed that Trolox C phenoxyl
      radical (TxO(*)) was the only paramagnetic species detected either in the absence
      or in the presence of CO(2). Stopped-flow spectrophotometry experiments revealed
      a sequential reaction mechanism, with the intermediacy of TxO(*) and the
      production of Trolox C quinone (TxQ). Reactions were zero-order with respect to
      TxOH and first-order in peroxynitrite and CO(2), demonstrating that the reaction
      of peroxynitrite with TxOH is indirect. In agreement, TxOH was unable to inhibit
      the direct peroxynitrite-mediated oxidation of methionine to methionine
      sulfoxide. TxOH oxidation yields to TxO(*) and TxQ with respect to peroxynitrite
      were approximately 60 and approximately 31%, respectively, and increased to
      approximately 73 and approximately 40%, respectively, in the presence of CO(2).
      At peroxynitrite excess over TxOH, the kinetics and mechanism of oxidation are
      more complex and involve the reactions of CO(3)(*)(-) with TxO(*) and the
      possible intermediacy of unstable NO(2)-TxOH adducts. Taken together, our results
      strongly support that H(+)- or CO(2)-catalyzed homolysis of peroxynitrite is
      required to cause TxOH, and hence, alpha-tocopherol oxidation.

PMID- 15487900
TI  - Determination of glycated nucleobases in human urine by a new monoclonal antibody
      specific for N2-carboxyethyl-2'-deoxyguanosine.
AB  - Sugars and sugar degradation products react in vivo readily with proteins
      (glycation) resulting in the formation of a heterogeneous group of reaction
      products, which are called advanced glycation end products (AGEs). AGEs notably
      change the structure and function of proteins so that extended protein-AGE
      formation is linked to complications such as nephropathy, atherosclerosis, and
      cataract. DNA can be glycated in vitro in a similar way as proteins, and the two
      diastereomers of N(2)-carboxyethyl-2'-deoxyguanosine (CEdG(A,B)) were identified
      as major DNA AGEs. It was postulated that DNA AGEs play an important role in
      aging, diabetes, and uremia. However, at the moment, sensitive methods to measure
      the extent and impact of DNA AGEs in vivo do not exist. In this study, we
      developed a monoclonal antibody, which recognized CEdG(A,B) with high affinity
      and specificity (MAb M-5.1.6). The I(50) value for CEdG(A,B) was 2.1 ng/mL,
      whereas other modified nuclueobases and AGE proteins showed negligible cross
      reactivity. Unmodified 2'-deoxyguanosine was only weakly recognized with an I(50)
      value > 600,000 ng/mL, which is the limit of solubility. MAb M-5.1.6 was then
      used to measure the urinary excretion of AGE-modified nucleobases in a
      competitive enzyme-linked immunosorbent assay. The recovery of CEdG(A,B) from
      human urine was between 87.4 and 99.7% with coefficients of variations between
      8.0 and 22.2%. The detection limit was 0.06 ng/mL, and the determination limit
      was 0.15 ng/mL with a linear range between 0.3 and 100 ng/mL. CEdG equivalents
      were analyzed in urine samples from 121 healthy volunteers, and concentrations
      between 1.2 and 117 ng CEdG equiv/mg creatinine were detected.

PMID- 15487901
TI  - Interaction of oxaliplatin, cisplatin, and carboplatin with hemoglobin and the
      resulting release of a heme group.
AB  - Oxaliplatin, carboplatin, and cisplatin are widely used to treat a number of
      cancers. While their DNA adducts are believed to cause cell death, the
      involvement of their protein adducts in the toxicity and action of these drugs is
      unclear. Here, we report the interactions of hemoglobin (Hb) with the three
      platinum (Pt) drugs, demonstrating the formation of Hb-Pt complexes and the
      release of a heme group from Hb. Oxaliplatin (0.05 microM) was able to form three
      major complexes with Hb (3-10 microM) after 1 h of incubation at room
      temperature, and these complexes accounted for approximately 60% of the total
      oxaliplatin. Cisplatin and carboplatin formed one major and two minor complexes
      only after 24 and 96 h of incubation, respectively. Incubation of these Pt drugs
      (0.05-10 microM) with whole blood of healthy volunteers and the analysis of red
      blood cells confirmed the relative ability of these Pt drugs binding to Hb. For
      the whole blood samples incubated with oxaliplatin and cisplatin for 24 h, only
      protein complexes were detected in red blood cells, indicating a complete binding
      of oxaliplatin and cisplatin to the protein. In contrast, carboplatin was
      partially bound; both the free and the protein-bound carboplatin species were
      detected in red blood cells. The binding of the Pt drugs to Hb was accompanied by
      the release of a heme group from Hb, which was monitored by size fractionation,
      chromatographic separation, and selective detection of both Pt- and iron (Fe)
      containing molecular species. The released heme was further identified by size
      fractionation and nanospray mass spectrometry. The findings of the Pt drug
      interaction with Hb and the dissociation of heme from Hb are potentially useful
      for a better understanding of the toxicity and side effects of these
      chemotherapeutic drugs.

PMID- 15487902
TI  - Fitness and physical activity in children with asthma.
AB  - Asthma remains the most common chronic disease in childhood, reportedly affecting
      up to 25% of children in Western urban environmental settings. There seems to be
      a common perception that asthmatic children have a reduced capacity for exercise.
      Surprisingly, there is conflicting evidence in the literature in relation to this
      position. In this review, we present an overview of the literature in which
      habitual physical activity and fitness levels, including aerobic fitness, of
      asthmatic and non-asthmatic children are compared. There is contradictory
      evidence regarding the aerobic fitness levels of asthmatic children and
      adolescents, and it remains unclear whether significant differences exist between
      asthmatic children and their non-asthmatic counterparts. There is limited
      information concerning the relative anaerobic fitness of asthmatic children and
      adolescents; however, this is also conflicting. During childhood and adolescence,
      asthmatic individuals seem to have physical activity levels comparable with those
      of the normal paediatric population. However, differences in physical activity
      levels may develop during the time of maturation from adolescence into adulthood.
      Accordingly, it is not possible to establish a definitive conclusion about the
      issue in either children or adults. Further research with well designed
      methodologies is needed in order to determine whether asthmatic children and
      adolescents have different aerobic fitness, anaerobic fitness and physical
      activity levels when compared with the normal paediatric population.

PMID- 15487903
TI  - Caffeine and ephedrine: physiological, metabolic and performance-enhancing
      effects.
AB  - Preparations containing caffeine and ephedrine have become increasingly popular
      among sportspersons in recent years as a means to enhance athletic performance.
      This is due to a slowly accumulating body of evidence suggesting that combination
      of the two drugs may be more efficacious than each one alone. Caffeine is a
      compound with documented ergogenicity in various exercise modalities, while
      ephedrine and related alkaloids have not been shown, as yet, to result in any
      significant performance improvements. Caffeine-ephedrine mixtures, however, have
      been reported in several instances to confer a greater ergogenic benefit than
      either drug by itself. Although data are limited and heterogeneous in nature to
      allow for reaching consensus, the increase in performance is a rather uniform
      finding as it has been observed during submaximal steady-state aerobic exercise,
      short- and long-distance running, maximal and supramaximal anaerobic cycling, as
      well as weight lifting. From the metabolic point of view, combined ingestion of
      caffeine and ephedrine has been observed to increase blood glucose and lactate
      concentrations during exercise, wheareas qualitatively similar effects on lipid
      fuels (free fatty acids and glycerol) are less pronounced. In parallel,
      epinephrine and dopamine concentrations are significantly increased, wheareas the
      effects on norepinephrine are less clear. With respect to pulmonary gas exchange
      during short-term intense exercise, no physiologically significant effects have
      been reported following ingestion of caffeine, ephedrine or their combination.
      Yet, during longer and/or more demanding efforts, some sporadic enhancements have
      indeed been shown. On the other hand, a relatively consistent cardiovascular
      manifestation of the latter preparation is an increase in heart rate, in addition
      to that caused by exercise alone. Finally, evidence to date strongly suggests
      that caffeine and ephedrine combined are quite effective in decreasing the rating
      of perceived exertion and this seems to be independent of the type of activity
      being performed. In general, our knowledge and understanding of the
      physiological, metabolic and performance-enhancing effects of caffeine-ephedrine
      mixtures are still in their infancy. Research in this field is probably hampered
      by sound ethical concerns that preclude administration of potentially hazardous
      substances to human volunteers. In contrast, while it is certainly true that
      caffeine and especially ephedrine have been associated with several acute adverse
      effects on health, athletes do not seem to be concerned with these, as long as
      they perceive that their performance will improve. In light of the fact that
      caffeine and ephedra alkaloids, but not ephedrine itself, have been removed from
      the list of banned substances, their use in sports can be expected to rise
      considerably in the foreseeable future. Caffeine-ephedra mixtures may thus become
      one of most popular ergogenic aids in the years to come and while they may indeed
      prove to be one of the most effective ones, and probably one of the few legal
      ones, whether they also turn out to be one of the most dangerous ones awaits to
      be witnessed.

PMID- 15487906
TI  - [Systemic nosocomial infection by yeasts].

PMID- 15487907
TI  - A review of Alternaria alternata sensitivity.
AB  - Sensitivity to fungi is a major risk factor for the development of asthma.
      However, the prevalence of fungal sensitivity in asthma is not completely
      understood. Nonetheless upward of 80% of asthmatic patients may be sensitized to
      one or more fungi. Fungal exposure occurs primarily from outdoors sources, but
      can occur in the indoor environment as well. Assessment of fungal exposure
      requires a multifaceted approach including measurement of airborne spores and
      culture techniques to identify the relevant organisms. Preventing intrusion of
      outdoor fungal spores into the indoor environment may be helpful in reducing
      allergic symptoms. Methods to abate indoor fungal growth include reduction of
      indoor humidity and removal of water sources. Patients with fungal sensitivity
      should be advised to avoid exposure as much as possible. For patients who have
      failed to respond to environmental control measures and appropriate medications,
      it may be reasonable to consider specific immunotherapy. The application of
      molecular biology techniques to the study of allergens has enhanced the
      researcher's ability to produce Alternaria allergens in quantity, to determine
      their biological relevance, as well as to evaluate mechanisms of Alternaria
      sensitivity. We look forward to new developments and improved treatments through
      modulation of the immune response with molecularly produced and well
      characterized fungal allergy.

PMID- 15487905
TI  - Soccer injuries: a review on incidence and prevention.
AB  - Several investigators have studied the incidence and causes of soccer injuries in
      male professional players; however, epidemiological data on injuries in female
      soccer players are limited. From the data presented, it can be estimated that, on
      average, every elite male soccer player incurs approximately one performance
      limiting injury each year. Nine studies on the prevention of soccer injuries were
      found in the literature. There is some evidence that multi-modal intervention
      programmes result in a general reduction in injuries. Ankle sprains can be
      prevented by external ankle supports and proprioceptive/coordination training,
      especially in athletes with previous ankle sprains. With regard to severe knee
      injuries, the results of prevention studies are partly inconclusive; however,
      training of neuromuscular and proprioceptive performance as well as improvement
      of jumping and landing technique seem to decrease the incidence of anterior
      cruciate ligament injuries in female athletes. Prevention programmes are likely
      to be more effective in groups with an increased risk of injury. More
      methodologically well-designed studies are required to evaluate the effects of
      specific preventive interventions.

PMID- 15487908
TI  - Inter and intra-specific genetic variability of oral Candida species.
AB  - In this report, strains of five different Candida species (Candida albicans,
      Candida guilliermondii, Candida tropicalis, Candida krusei, and Candida
      parapsilosis) isolated from healthy human oral cavities as well as their
      respective type-strains were used in order to establish the genetic diversity
      existing among the different species and within a certain species, by the
      analysis of their electrophoretic alloenzyme patterns. These profiles were
      analyzed for their band positions in the gels, which allowed to group the strains
      of the same species in species-specific clusters and to treat them as conspecific
      populations. A total of thirteen enzymatic loci were obtained (ACO, ADH1, ADH2,
      CAT, G6PDH, GDH, GOT, IDH1, IDH2, LAP, LDH, PER, and SOD). The allelic
      frequencies (p) and the heterozygosity (h) for all the thirteen loci were
      determined by diversity index formulas. The GST index is the estimated proportion
      of genetic diversity that was applied in order to establish inter and intra
      populational diversity, which, for our results, indicated that 37.75% of total
      genetic diversity was attributable to differences among the species and the
      remaining 62.25% was attributable to differences within these populations. An
      Euclidian distance dendrogram for the different conspecific populations was
      built, showing that C. guilliermondii grouped first with C. tropicalis and thus
      formed a expanded cluster with C. albicans. This cluster combined later with
      another one composed by C. parapsilosis and C. krusei. Comparing our results to
      the others that were obtained by different molecular techniques, we have observed
      that the clustering hierarchies follow different paths of organization, varying
      according to the methodology employed.

PMID- 15487904
TI  - Physiological changes associated with the pre-event taper in athletes.
AB  - Some of the physiological changes associated with the taper and their
      relationship with athletic performance are now known. Since the 1980s a number of
      studies have examined various physiological responses associated with the
      cardiorespiratory, metabolic, hormonal, neuromuscular and immunological systems
      during the pre-event taper across a number of sports. Changes in the
      cardiorespiratory system may include an increase in maximal oxygen uptake, but
      this is not a necessary prerequisite for taper-induced gains in performance.
      Oxygen uptake at a given submaximal exercise intensity can decrease during the
      taper, but this response is more likely to occur in less-skilled athletes.
      Resting, maximal and submaximal heart rates do not change, unless athletes show
      clear signs of overreaching before the taper. Blood pressure, cardiac dimensions
      and ventilatory function are generally stable, but submaximal ventilation may
      decrease. Possible haematological changes include increased blood and red cell
      volume, haemoglobin, haematocrit, reticulocytes and haptoglobin, and decreased
      red cell distribution width. These changes in the taper suggest a positive
      balance between haemolysis and erythropoiesis, likely to contribute to
      performance gains. Metabolic changes during the taper include: a reduced daily
      energy expenditure; slightly reduced or stable respiratory exchange ratio;
      increased peak blood lactate concentration; and decreased or unchanged blood
      lactate at submaximal intensities. Blood ammonia concentrations show inconsistent
      trends, muscle glycogen concentration increases progressively and calcium
      retention mechanisms seem to be triggered during the taper. Reduced blood
      creatine kinase concentrations suggest recovery from training stress and muscle
      damage, but other biochemical markers of training stress and performance capacity
      are largely unaffected by the taper. Hormonal markers such as testosterone,
      cortisol, testosterone : cortisol ratio, 24-hour urinary cortisol : cortisone
      ratio, plasma and urinary catecholamines, growth hormone and insulin-like growth
      factor-1 are sometimes affected and changes can correlate with changes in an
      athlete's performance capacity. From a neuromuscular perspective, the taper
      usually results in markedly increased muscular strength and power, often
      associated with performance gains at the muscular and whole body level. Oxidative
      enzyme activities can increase, along with positive changes in single muscle
      fibre size, metabolic properties and contractile properties. Limited research on
      the influence of the taper on athletes' immune status indicates that small
      changes in immune cells, immunoglobulins and cytokines are unlikely to compromise
      overall immunological protection. The pre-event taper may also be characterised
      by psychological changes in the athlete, including a reduction in total mood
      disturbance and somatic complaints, improved somatic relaxation and self-assessed
      physical conditioning scores, reduced perception of effort and improved quality
      of sleep. These changes are often associated with improved post-taper
      performances. Mathematical models indicate that the physiological changes
      associated with the taper are the result of a restoration of previously impaired
      physiological capacities (fatigue and adaptation model), and the capacity to
      tolerate training and respond effectively to training undertaken during the taper
      (variable dose-response model). Finally, it is important to note that some or all
      of the described physiological and psychological changes associated with the
      taper occur simultaneously, which underpins the integrative nature of
      relationships between these changes and performance enhancement.

PMID- 15487909
TI  - [Optimization of the conditions for RAPD-PCR of Candida spp. and Cryptococcus
      spp].
AB  - In this study, we determined the optimal RAPD amplification conditions to obtain
      genetic molecular markers for the rapid and accurate identification of
      Cryptococcus spp. and Candida spp. The following parameters are modified:
      template DNA, DNA polymerase, magnesium cloride and primer concentration;
      denaturation, annealing and extension time, temperature of annealing and thermal
      cycles. After the optimization, reliable and reproducible RAPD patterns are
      obtained.

PMID- 15487910
TI  - [Invasive aspergillosis in Castilla y Leon and Cantabria: years 1998 and 1999].
AB  - BACKGROUND: Invasive aspergillosis (IA) is a life-threatening mycosis showing a
      fast clinical course, affecting immunosupressed people particularly patients
      suffering leukemia or following organ transplantation programs. The aim of this
      work is to show epidemiologycal concerns about IA in Castilla y Leon and
      Cantabria: the disease's incidence, the main clinical presentations, the
      underlaying diseases and diagnostic rules in the laboratory. PATIENTS AND
      METHODS: 50 cases of IA were obtained from the countries of Castilla y Leon and
      Cantabria in a two-years (1998-1999) retrospective study. Epidemiology, clinical
      and diagnostic features including the 14 main institutions were registered and
      accounted in a single data base. RESULTS: The majority of IA cases were recorded
      in major institutions possessing haematology units or organ transplantation
      programs. Invasive pulmonary aspergillosis was the main feature (39/50 cases)
      showing serious underlying diseases (25/50 cases) or following organ
      transplantation programs (15/50 cases). Certain diagnosis was obtained for only
      ten cases of invasive pulmonary aspergillosis and eleven cases of extrapulmonary
      stages of IA. In a high number of cases (44/50 cases) conventional
      microbiological procedures (42/50 showing positive cultures) were developed.
      Serology investigations were undertaken in eight cases. Serological issues
      relying on anti-Aspergillus antibodies showed no diagnostic value. Aspergillus
      fumigatus was the most common species involved in IA (33/44 cases). CONCLUSIONS:
      A low incidence of the disease in this country was reported: with 50 cases in 14
      hospital institutions during a two-year period. We observed most cases in large
      hospital centres performing transplant operations. Invasive pulmonary
      aspergillosis was the main clinical setting in immunosupressed patients.
      Microbiology diagnostic issues relied on conventional methods in particularly on
      culture.

PMID- 15487911
TI  - [Fungal keratitis in the State of Parana-Brazil: clinical, epidemiological and
      diagnostic findings].
AB  - Fungal keratites is more prevalent in tropical and subtropical regions, such as
      Brazil, and causes high morbidity. Usually, it is preceded by underlying
      conditions like ocular trauma or immunosuppression. The diagnosis is confirmed by
      the demonstration of the etiologic agent in the clinical specimen. Data were
      analysed from 49 patients with fungal keratitis observed in Ophthalmologic
      Division of Hospital de Clinicas, Federal University of Parana, from 1983 to
      1997. The diagnosis was confirmed by culture and/ or direct examination. Of the
      cases studied, 22% were diagnosed only by direct examination; 50% by isolation in
      culture and 26% by the association of the both methods. The most prevalent
      etiologic agents were: Fusarium sp. (32%), Aspergillus sp. (16,5%) and
      Penicillium sp. (10%).

PMID- 15487912
TI  - Fungal flora of the digestive tract of Panstrongylus megistus (Reduviidae) used
      for experimental xenodiagnosis of Trypanosoma (Schizotripanum) cruzi Chagas,
      1909.
AB  - A survey of the fungi isolated from the digestive tract of Panstrongylus megistus
      (insects vectors from Chagas' disease) used on xenodiagnosis was carried out. Two
      hundred and fourteen fungal strains were isolated from 180 nymphs. Aspergillus
      and Penicillium were the most predominant genera and some of their species were
      new records concerning insects. A great reduction in the fungal population was
      observed in the material that was positive for Trypanosoma cruzi.

PMID- 15487913
TI  - Aflatoxin synthesis in corn fields in Guanajuato, Mexico.
AB  - Aflatoxin contamination of corn is an important problem internationally,
      particularly in tropical and subtropical conditions that favor infection and
      synthesis by Aspergillus. Environmental conditions (drought) and agronomic
      practices i.e. N fertilization have been reported as favorable to aflatoxin
      synthesis in the field. This study was undertaken to investigate whether the
      contamination of corn commonly observed in stored conditions in this important
      corn producing region of Mexico known as "El Bajio" is related to infection by
      Aspergillus under field conditions. Results using three corn hybrids of
      recognized susceptibility to infection showed that corn ears artificially
      inoculated in the field with a toxigenic strain of Aspergillus parasiticus
      presented a low content of aflatoxin ranging from 13.6 to 24.7 microg Kg(-1). No
      significant differences were observed between the hybrids tested. Similarly, N
      fertilization practices, 260 Kg N ha(-1), applied at sowing did not have an
      effect on the extent of the contamination observed of 6.2 and 19.3 mg of
      aflatoxin kg(-1) in natural infected and inoculated samples with A. parasiticus
      NRRL 2999, respectively. Our data suggest that the cases of aflatoxin
      contamination of corn in this part of Mexico are not related to infection
      occurring during the crops growing period but most probably to poor storage
      conditions of corn.

PMID- 15487914
TI  - [Tinea capitis by Microsporum audouinii].
AB  - We report the case of a four year-old girl from Equatorial Guinea who had been
      living in Spain for the last month. She presented several alopecic patches on the
      scalp. The direct study of the hair with 40% KOH showed an ectothrix infection
      and the mycological study revealed the etiologic agent was Microsporum audouinii.
      We present this case because of its rarity in our country and we point out the
      increasing interest of the imported tineas due to immigration from African
      countries.

PMID- 15487915
TI  - The taxonomic status of Lacazia loboi and Rhinosporidium seeberi has been finally
      resolved with the use of molecular tools.

PMID- 15487916
TI  - [Epidemiological study of cryptococcosis in Spain: first results].
AB  - The study constitutes an approach to the knowledge of the epidemiology of
      cryptococosis in Spain. For detection of cases 167 Spanish hospitals were
      contacted. All cases included were accompanied by the correspondent isolate of
      Cryptococcus neoformans, together with clinical, demographic and mycological
      data. Results obtained from January 1998 to end of December 1999 are analysed and
      presented here. Fifty-six Spanish hospitals reported 58 cases of cryptococcosis;
      only 43 of them were adequately documented and accompanied by the clinical
      isolate. The results showed a higher incidence in males (88.4%) than in females
      (11.6%); being most frequently affected those between 30 and 40 years old
      (48.8%). The 84.6% (33) corresponded to new cases and 15.4% (6) to relapses of
      the disease. The HIV infection was the most frequent risk factor reported (86%)
      and, for 29.7% (11) of them, cryptococcosis was the AIDS defining disease. For
      the diagnosis, CSF analysis showed the best results (India ink; culture and
      antigen detection). All strains collected (100%) corresponded to C. neoformans
      variety neoformans. Serotypes distribution was 45.5% for serotype A and 22.7% for
      each of serotypes D and AD.

PMID- 15487917
TI  - [Evaluation of Chromalbicans Agar for presumptive identification of Candida
      albicans].
AB  - The utility of Chromalbicans Agar (Biolife Italiana, Milano, Italy) was evaluated
      with 723 clinical isolates and type culture collection strains from different
      genera including Candida, Cryptococcus, Pichia, Rhodotorula, Saccharomyces,
      Trichosporon y Zygosaccharomyces. Presumptive identification was confirmed by
      germ tube test and carbohydrate assimilation on API-ATB ID 32C (bioMerieux,
      France). Growth on Chromalbicans Agar was very useful for the presumptive
      identification of C. albicans isolates, and sensitivity and specificity values
      were significantly high (>97%), since a very low number of isolates were found to
      be false negative or false positive.

PMID- 15487918
TI  - [Pityriasis versicolor in infants under one year of age. A report of 92 cases].
AB  - BACKGROUND: Pityriasis versicolor is a common world wide mycosis caused by
      Malassezia spp. and by Malassezia furfur sensu lato. It is uncommon in children
      and almost always with atypical clinical manifestations. It has been reported as
      exceptional in children under one year of age. OBJECTIVES: To determine the
      clinical and epidemiological data of pityriasis versicolor in infants under one
      year of age. METHODOLOGY: This is a restrospective and transversal study of
      pityriasis versicolor in the pediatric population studied during one year at the
      Instituto Dermatologico y Cirugia de Piel in Dominican Republic. Everyone with a
      Malassezia spp. positive scotch tape test with methylene blue were included.
      RESULTS: Among 5160 cases of pityriasis versicolor where 797 were children, we
      found 92 (11%) cases under one year of age. The clinical manifestations were
      atypical and the most commonly affected zone was the face (81%) and thorax (16%).
      Less frequently the neck (8.6%) and upper and lower limbs (5%) were affected.
      CONCLUSIONS: Pityriasis versicolor in children under one year of age is not
      exceptional in humid and hot climates. The hypochromic lesions are the main
      clinical manifestation and the most affected site is the face. Diagnosis is easy
      and cheap with a positive Malassezia spp. scotch tape test with methylene blue.

PMID- 15487919
TI  - [In vitro susceptibility of dematiaceous fungi to ten antifungal drugs using an
      agar diffusion test].
AB  - We assessed the usefulness of an agar diffusion method, NeoSensitabs, to
      determine in vitro sensitivity of 52 isolates of dematiaceous filamentous fungi
      against ten antifungal agents: amphotericin B, 5-fluorocytosine, ketoconazole,
      fluconazole, itraconazole, terbinafine, bifonazole, miconazole, clotrimazole, and
      griseofulvin. For the preparation of the inoculum, a spectrophotometric method
      including both Shadomy and Casitone agar (CAS) culture media was used.
      Dematiaceous filamentous fungi were sensitive to itraconazole, terbinafine and
      bifonazole. Ketoconazole (90.4%), miconazole (71%), and clotrimazole (46%) showed
      a variable susceptibility pattern. Most species were resistant to griseofulvin
      and fluconazole (96%). All isolates were resistant to 5-fluorocytosine. Sixty
      three percent of strains were susceptible to amphotericin B and 28.8% resistant.
      Inhibition zones in the antifungal susceptibility testing did not vary according
      to culture medium, although fungal growth was better in CAS. Variations in
      antifungal sensitivity in Exophiala spinifera and Fonsecaea pedrosoi spp. would
      justify an in vitro susceptibility study when indicating antifungal therapy.
      These results show that NeoSensitabs agar diffusion method is simple, rapid, and
      low-cost and can be available to many clinical laboratories for the study of in
      vitro sensitivity of dematiceous moulds.

PMID- 15487920
TI  - Selection of strains of Lentinula edodes and Lentinula boryana adapted for
      efficient mycelial growth on wheat straw.
AB  - Mycelial growth rates are presented for 11 strains of Lentinula edodes and six
      strains of Lentinula boryana cultivated on solid media: derived from malt extract
      (MEA); malt yeast extract (YMEA); and, YMEA plus soluble lignin derivatives
      (YMEA+WSLD). The results were compared with data for mycelial growth rates, of
      the same strains cultivated on substrates derived from wheat straw treated at
      different temperatures (50, 65, 75 and autoclaving at 121 degrees C). In general,
      the addition of WSLD significantly reduced mycelial growth rates in both species.
      The greatest mycelial growth rate was obtained on sterilized straw at 121 degrees
      C for the majority of strains. However, this growth was not significantly
      different from that obtained at 75 degrees C. L. edodes showed greater growth
      rates than L. boryana. The feasibility of using estimates of mycelial growth rate
      on YMEA and YMEA+WSLD are discussed as possible indicators of a strain's
      potential for mycelial growth on substrates derived from wheat straw.

PMID- 15487921
TI  - Biochemical markers in taxonomy of the genus Cunninghamella.
AB  - The chemical composition of fatty acids and ubiquinones was studied in 18 strains
      of Cunninghamella, to establish quantitative and qualitative differences within
      the genus. Fatty acids analysis has shown the presence of four groups. Ubiquinone
      analysis, through high performance liquid chromatography (HPLC), demonstrated the
      existence of three different groups based on the ubiquinone type. The average
      percentage of fatty acids of the species Cunninghamella elegans and
      Cunninghamella bertholletiae, show variations in linolenic and stearic acids,
      suggesting the possibility of differentiation between the two species.

PMID- 15487922
TI  - Varietes and serotypes of Cryptococcus neoformans clinical isolates in Colombia.
AB  - The aim of this study was to contribute to the knowledge of the geographic
      distribution of Cryptococcus neoformans varieties, in Colombian patients, and to
      determine the mating types of such varieties. A total of 370 clinical isolates
      were studied. C. neoformans var. neoformans was identified in 95.2% of them. C.
      neoformans var. gattii in 4.8%, 4.5% being serotype B and 0.3%, serotype C. Fifty
      five of the 74 (74%) isolates studied were mating type "alpha", all of them C.
      neoformans var. neoformans. Serotype C had been previously reported only once in
      South American countries.

PMID- 15487923
TI  - Experimental infection of almond trees seedlings (Terminalia catappa) with an
      environmental isolate of Cryptococcus neoformans var. gattii, serotype C.
AB  - Recently, our laboratory reported the isolation of Cryptococcus neoformans var.
      gattii, serotype C for the first time from almond trees (Terminalia catappa)
      detritus. The aim of the present study was to establish the survival of C.
      neoformans in almond trees seedlings. Thirty seedlings were infected in the stems
      and samples were taken and processed at different times and by different
      techniques. No morphological alterations (macro or microscopic) were observed in
      the infected plants. However, C. neoformans was found to be viable for at least
      100 days after infection. These data constitute our first approach towards the
      understanding of the yeast interactions with a host-plant.

PMID- 15487924
TI  - Sporotrichosis in patient with AIDS: report of a case and review.
AB  - Although sporotrichosis is not an AIDS-defining infection, reports of
      sporotrichosis in individuals infected with HIV are increasing. We report an
      unusual case of this co-infection in a man with progressive deep cutaneous
      ulcerations with numerous pleomorphic yeast cells of Sporothrix schenckii. In
      addition a review of the literature on this subject was carried out and commented
      upon.

PMID- 15487925
TI  - Recurrence of sporotrichosis in cats with zoonotic involvement.
AB  - The aim of this work is to describe the prevalence of the disease in the same
      cattery after three years, and to report a case of human sporotrichosis following
      a cat scratch. In May 1997, four felines presenting a cachexy state and ulcerous
      lesions on the head, nose and limbs were examined in a veterinary clinic in the
      town of Rio Grande (RS-Brazil). Exudate and crusts were collected for
      microbiological diagnosis. The cat's owner returned to the clinic reporting that
      another eleven felines presented similar lesions. She had ulcerous lesions on her
      hand and ascending lymphangitis. She was conducted to medical examination where
      exudate and crusts from the lesions were collected and after the culture
      Sporothrix schenckii was isolated. After three years the same person sought
      veterinary assistance for seven more cats with similar lesions to the five
      previously described. Microbiological tests resulted again in isolation of S.
      schenckii. Treatment with potassium iodine was effective for the cure of human
      sporotrichosis, whereas for the felines it showed toxic effect. Only one showed
      regression of the disease while all the others presented progression of the
      lesions or even death. The authors call attention to the possible persistence of
      S. schenckii in cat populations.

PMID- 15487926
TI  - [Natural contamination with mycotoxins in forage maize and green coffee in
      Nayarit State (Mexico)].
AB  - The presence of mycotoxins in forage maize (zearalenone, fumonisin B1, T-2 toxin
      and diacetoxyscirpenol) and green coffee (ochratoxin A) from Nayarit State
      (Mexico) has been studied. All maize samples analyzed showed fumonisin B1
      contamination, with an average concentration of 2,541 microg/kg. Fifteen percent
      of the samples contained zearalenone, with an average concentration of 1,610
      microg/kg. Only one sample showed T-2 toxin contamination (7 microg/kg), and no
      diacetoxyscirpenol was detected. Sixty-seven per cent of green coffee samples
      were contaminated with ochratoxin A, with an average concentration of 30.1
      microg/kg. This is the first study about mycotoxins developed in Nayarit and it
      has shown that mycotoxin contamination is a real problem in both foodstuffs
      studied.

PMID- 15487928
TI  - Pickles, pectin, and penicillin.
AB  - My professional life has been devoted to the study of microbial products and
      their biosynthesis, regulation, and overproduction. These have included primary
      metabolites (glutamic acid, tryptophan, inosinic acid, guanylic acid, vitamin
      B(12), riboflavin, pantothenic acid, ethanol, and lactic acid) and secondary
      metabolites (penicillin, cephalosporins, streptomycin, fosfomycin, gramicidin S,
      rapamycin, indolmycin, microcin B17, fumagillin, mycotoxins, Monascus pigments,
      and tetramethylpyrazine). Other areas included microbial nutrition, strain
      improvement, bioconversions of statins and beta-lactams, sporulation and
      germination, plasmid stability, gel microdroplets, and the production of double
      stranded RNA, the polymer xanthan, and enzymes (polygalacturonase, protease,
      cellulase). Most of the studies were carried out with me by devoted and
      hardworking industrial scientists for 15 years at Merck & Co. and by similarly
      characterized students, postdoctorals, and visiting scientists during my 32 years
      at the Massachusetts Institute of Technology. I owe much of my success to my
      mentors from academia and industry. My recent research activities with
      undergraduate students at the Charles A. Dana Research Institute for Scientists
      Emeriti (R.I.S.E.) at Drew University have been very rewarding and are allowing
      me to continue my career.

PMID- 15487929
TI  - Anaerobic microbial dehalogenation.
AB  - The natural production and anthropogenic release of halogenated hydrocarbons into
      the environment has been the likely driving force for the evolution of an
      unexpectedly high microbial capacity to dehalogenate different classes of
      xenobiotic haloorganics. This contribution provides an update on the current
      knowledge on metabolic and phylogenetic diversity of anaerobic microorganisms
      that are capable of dehalogenating--or completely mineralizing--halogenated
      hydrocarbons by fermentative, oxidative, or reductive pathways. In particular,
      research of the past decade has focused on halorespiring anaerobes, which couple
      the dehalogenation by dedicated enzyme systems to the generation of energy by
      electron transport-driven phosphorylation. Significant advances in the
      biochemistry and molecular genetics of degradation pathways have revealed
      mechanistic and structural similarities between dehalogenating enzymes from
      phylogenetically distinct anaerobes. The availability of two almost complete
      genome sequences of halorespiring isolates recently enabled comparative and
      functional genomics approaches, setting the stage for the further exploitation of
      halorespiring and other anaerobic dehalogenating microbes as dedicated degraders
      in biological remediation processes.

PMID- 15487930
TI  - Signaling in myxobacteria.
AB  - Myxobacteria use soluble and cell-contact signals during their starvation-induced
      formation of fruiting bodies. These signals coordinate developmental gene
      expression with the cell movements that build fruiting bodies. Early in
      development, the quorum-sensing A-signal in Myxococcus xanthus helps to assess
      starvation and induce the first stage of aggregation. Later, the morphogenetic C
      signal helps to pattern cell movement and shape the fruiting body. C-signal is a
      17-kDa cell surface protein that signals by contact between the ends of two
      cells. The number of C-signal molecules per cell rises 100-fold from the
      beginning of fruiting body development to the end, when spores are formed.
      Traveling waves, streams, and sporulation have increasing thresholds for C-signal
      activity, and this progression ensures that spores form inside fruiting bodies.

PMID- 15487931
TI  - Anaerobic oxidation of methane and ammonium.
AB  - Anaerobic oxidation of methane and ammonium are two different processes catalyzed
      by completely unrelated microorganisms. Still, the two processes do have many
      interesting aspects in common. First, both of them were once deemed biochemically
      impossible and nonexistent in nature, but have now been identified as major
      factors in global carbon and nitrogen cycling. Second, the microorganisms
      responsible for both processes cannot be grown in pure culture yet; their
      detection and identification were based on molecular ecology, tracer studies, use
      of lipid biomarkers, and enrichment cultures. Third, these microorganisms grow
      extremely slowly (doubling time from weeks to months). Fourth, both processes
      have a good potential for application in biotechnology. Because both anaerobic
      methane and ammonium oxidation have been separately and excellently reviewed
      elsewhere, we focus on aspects of interest in the context of current developments
      in microbiology and explore the added value of reviewing these two processes in
      one place.

PMID- 15487932
TI  - Selection for gene clustering by tandem duplication.
AB  - In prokaryotic genomes, related genes are frequently clustered in operons and
      higher-order arrangements that reflect functional context. Organization emerges
      despite rearrangements that constantly shuffle gene and operon order. Evidence is
      presented that the tandem duplication of related genes acts as a driving
      evolutionary force in the origin and maintenance of clusters. Gene amplification
      can be viewed as a dynamic and reversible regulatory mechanism that facilitates
      adaptation to variable environments. Clustered genes confer selective benefits
      via their ability to be coamplified. During evolution, rearrangements that bring
      together related genes can be selected if they increase the fitness of the
      organism in which they reside. Similarly, the benefits of gene amplification can
      prevent the dispersal of existing clusters. Examples of frequent and spontaneous
      amplification of large genomic fragments are provided. The possibility is raised
      that tandem gene duplication works in concert with horizontal gene transfer as
      interrelated evolutionary forces for gene clustering.

PMID- 15487933
TI  - The Vibrio shiloi/Oculina patagonica model system of coral bleaching.
AB  - The scleractinian coral Oculina patagonica undergoes bleaching (loss of its
      endosymbiotic zooxanthellae) every summer in the eastern Mediterranean Sea when
      seawater temperatures rise. The causative agent of the disease is Vibrio shiloi.
      The pathogen adheres to a beta-galactoside-containing receptor in the coral
      mucus, penetrates into epithelial cells, differentiates into a viable-but-not
      culturable form, multiplies, and produces a proline-rich peptide toxin that
      inhibits photosynthesis of the zooxanthellae in the presence of ammonia. Several
      of the virulence factors, such as adhesin, toxin, and superoxide dismutase, are
      produced only at the elevated summer seawater temperatures. The fireworm
      Hermodice carunculata is a winter reservoir and spring/summer vector for V.
      shiloi. The generality of the bacterial hypothesis of coral bleaching is
      discussed.

PMID- 15487934
TI  - Stationary-phase physiology.
AB  - Bacteria enjoy an infinite capacity for reproduction as long as they reside in an
      environment supporting growth. However, their rapid growth and efficient
      metabolism ultimately results in depletion of growth-supporting substrates and
      the population of cells enters a phase defined as the stationary phase of growth.
      In this phase, their reproductive ability is gradually lost. The molecular
      mechanism underlying this cellular degeneration has not been fully deciphered.
      Still, recent analysis of the physiology and molecular biology of stationary
      phase E. coli cells has revealed interesting similarities to the aging process of
      higher organisms. The similarities include increased oxidation of cellular
      constituents and its target specificity, the role of antioxidants and oxygen
      tension in determining life span, and an apparent trade-off between activities
      related to reproduction and survival.

PMID- 15487935
TI  - Viral error catastrophe by mutagenic nucleosides.
AB  - Riboviruses and retroviruses have the highest rates of mutations of any known
      organism. Increasing the mutation rate of these viruses could exceed the error
      threshold for viability of a viral population within a host. Recent experiments
      with mutagenic nucleoside analogs validate this new approach to treating
      infection of RNA viruses. Lethal mutagenesis with HIV-infected cells in culture
      has been documented and has been postulated to be the mechanism for treatment of
      hepatitis C with ribavirin. We consider the viral dynamics involved in the
      formation of a quasispecies, the choice of mutagenic nucleoside analogs, and the
      studies that have demonstrated the feasibility of lethal mutagenesis.

PMID- 15487936
TI  - The ecology and genetics of microbial diversity.
AB  - Natural communities of microbes are often diverse, a fact that is difficult to
      reconcile with the action of natural selection in simple, uniform environments.
      We suggest that this apparent paradox may be resolved by considering the origin
      and fate of diversity in an explicitly ecological context. Here, we review
      insights into the ecological and genetic causes of diversity that stem from
      experiments with microbial populations evolving in the defined conditions of the
      laboratory environment. These studies highlight the importance of environmental
      structure in governing the fate of diversity and shed light on the genetic
      mechanisms generating diversity. We conclude by emphasizing the importance of
      placing detailed molecular-level studies within the context of a sound ecological
      and evolutionary framework.

PMID- 15487937
TI  - Ribosomal crystallography: initiation, peptide bond formation, and amino acid
      polymerization are hampered by antibiotics.
AB  - High-resolution structures of ribosomal complexes revealed that minute amounts of
      clinically relevant antibiotics hamper protein biosynthesis by limiting ribosomal
      mobility or perturbing its elaborate architecture, designed for navigating and
      controlling peptide bond formation and continuous amino acid polymerization. To
      accomplish this, the ribosome contributes positional rather than chemical
      catalysis, provides remote interactions governing accurate substrate alignment
      within the flexible peptidyl-transferase center (PTC) pocket, and ensures nascent
      protein chirality through spatial limitations. Peptide bond formation is
      concurrent with aminoacylated-tRNA 3' end translocation and is performed by a
      rotatory motion around the axis of a sizable ribosomal symmetry-related region,
      which is located around the PTC in all known crystal structures. Guided by
      ribosomal-RNA scaffold along an exact pattern, the rotatory motion results in
      stereochemistry that is optimal for peptide bond formation and for nascent
      protein entrance into the exit tunnel, the main target of antibiotics targeting
      ribosomes. By connecting the PTC, the decoding center, and the tRNA entrance and
      exit regions, the symmetry-related region can transfer intraribosomal signals,
      guaranteeing smooth processivity of amino acid polymerization.

PMID- 15487938
TI  - Herpes vector-mediated gene transfer in treatment of diseases of the nervous
      system.
AB  - Vectors constructed from recombinant herpes simplex virus (HSV) have special
      utility for gene transfer to the nervous system. Nonreplicating vectors created
      by deletion of essential immediate early genes can be propagated to high titers
      on complementing cell lines that provide the missing gene product(s) in trans.
      Direct inoculation of these vectors into neural parenchyma is effective in rodent
      models of brain tumor, Parkinson disease, spinal cord injury, and spinal root
      trauma. Subcutaneous inoculation of the HSV vectors can be used to transduce
      neurons of the dorsal root ganglion to provide a therapeutic effect in models of
      polyneuropathy and chronic regional pain. In human trials, direct injection of
      replication-competent HSV into brain tumors has proven safe. Human trials of
      nonreplicating HSV gene transfer by direct inoculation for treatment of
      glioblastoma and HSV gene transfer by subcutaneous inoculation for the treatment
      of chronic intractable pain should commence soon.

PMID- 15487939
TI  - Early molecular investigations of lichen-forming symbionts: 1986-2001*.
AB  - From the mid-1980s the symbionts in lichen associations, heterotrophic fungi and
      photosynthetic algae or cyanobacteria, were the subject of increasing numbers of
      molecular investigations. Many of the studies examined the phylogenetic placement
      of the individual symbiotic partners with their free-living relatives, refining
      their nomenclature and classification. Resulting phylogenies permitted the
      mapping of transitions to and from lichenization and stimulated discussion of the
      relative ease of gaining and losing symbiotic lifestyles. Comparing symbiont
      phylogenies both rejected strict cospeciation and mirrored phylogenies and hinted
      at more complex forces of coevolution, including symbiont switching and
      selection. Studies at the species and population levels examined patterns of
      species delimitation and geographic dispersion and processes such as gene flow,
      self-fertilization, and founder effect. Significant genetic variation often was
      associated with mobile elements, group I and spliceosomal introns. This review
      examines the influence of molecular investigation on lichenology during this
      first 15 years.

PMID- 15487940
TI  - The small RNA regulators of Escherichia coli: roles and mechanisms*.
AB  - Small noncoding RNAs have been found in all organisms, primarily as regulators of
      translation and message stability. The most exhaustive searches have taken place
      in E. coli, resulting in identification of more than 50 small RNAs, or 1%-2% of
      the number of protein-coding genes. One large class of these small RNAs uses the
      RNA chaperone Hfq; members of this class act by pairing to target messenger RNAs.
      Among the members of this class are DsrA and RprA, which positively regulate rpoS
      translation, OxyS, which negatively regulates rpoS translation and fhlA
      translation, RyhB, which reapportions iron use in the cell by downregulating
      translation of many genes that encode Fe-containing proteins, and Spot 42, which
      changes the polarity of translation in the gal operon. The promoters of these
      small RNAs are tightly regulated, frequently as part of well-understood regulons.
      Lessons learned from the study of small RNAs in E. coli can be applied to finding
      these important regulators in other organisms.

PMID- 15487941
TI  - Johne's disease, inflammatory bowel disease, and Mycobacterium paratuberculosis.
AB  - Johne's disease is a chronic diarrhea affecting all ruminants. Mycobacterium
      avium subsp. paratuberculosis (MAP), a slowly growing mycobacteria, is the
      etiologic agent. There is also a concern that MAP might be a causative agent of
      some cases of inflammatory bowel disease in humans, especially Crohn's disease.
      Food products including pasteurized bovine milk have been suggested as potential
      sources of human infection. This review addresses microbial factors that may
      contribute to its pathogenicity. In addition, the experimental evidence defining
      MAP as the cause of Johne's disease and the issues and controversies surrounding
      its potential pathogenic role in humans are discussed.

PMID- 15487942
TI  - Molecular and cellular basis of bartonella pathogenesis.
AB  - The genus Bartonella comprises several important human pathogens that cause a
      wide range of clinical manifestations: cat-scratch disease, trench fever,
      Carrion's disease, bacteremia with fever, bacillary angiomatosis and peliosis,
      endocarditis, and neuroretinitis. Common features of bartonellae include
      transmission by blood-sucking arthropods and the specific interaction with
      endothelial cells and erythrocytes of their mammalian hosts. For each Bartonella
      species, the invasion and persistent intracellular colonization of erythrocytes
      are limited to a specific human or animal reservoir host. In contrast,
      endothelial cells are target host cells in probably all mammals, including
      humans. Bartonellae subvert multiple cellular functions of human endothelial
      cells, resulting in cell invasion, proinflammatory activation, suppression of
      apoptosis, and stimulation of proliferation, which may cumulate in
      vasoproliferative tumor growth. This review summarizes our understanding of
      Bartonella-host cell interactions and the molecular mechanisms of bacterial
      virulence and persistence. In addition, current controversies and unanswered
      questions in this area are highlighted.

PMID- 15487943
TI  - Cell-mediated immunity and the outcome of hepatitis C virus infection.
AB  - The hepatitis C virus (HCV) infects approximately three percent of the world's
      population. Some individuals resolve the infection spontaneously, but the
      majority develop persistent viremia that often causes progressive liver disease.
      There is an emerging consensus that cellular immune responses are essential for
      spontaneous resolution of acute hepatitis C and long-term protection from
      persistent infection. This review focuses on the recent advances in understanding
      mechanisms of protective immunity and why they fail in most infected individuals.
      The distinct yet complementary role of CD4+ and CD8+ T lymphocytes in this
      process is highlighted.

PMID- 15487944
TI  - Recent advances in the characterization of ambient pH regulation of gene
      expression in filamentous fungi and yeasts.
AB  - All microorganisms must adapt to the pH of their environment. One aspect of this
      adaptation, particularly important for organisms that grow over a wide pH range,
      is the ability to express appropriately genes whose roles ultimately involve
      functions at the cell surface or in the environment. Genes encoding permeases,
      secreted enzymes, enzymes involved in synthesis of exported metabolites such as
      toxins and antibiotics, and probably enzymes modifying secreted proteins
      posttranslationally all fall into this category. Here we discuss the most recent
      findings on the transcriptional regulatory system in fungi that enables such
      genes to be expressed only when the ambient pH is conducive to their ultimate
      functions. The intriguing issue of how pH is sensed and how the resulting signal
      is transmitted to the transcription factor involves at least one late endosome
      component. Proper functioning of the regulatory system responding to ambient pH
      is essential for fungal pathogenicity of both animals and plants.

PMID- 15487945
TI  - Biosynthesis of nonribosomal peptides1.
AB  - Bacteria and fungi use large multifunctional enzymes, the so-called nonribosomal
      peptide synthetases (NRPSs), to produce peptides of broad structural and
      biological activity. Biochemical studies have contributed substantially to the
      understanding of the key principles of these modular enzymes that can draw on a
      much larger number of catalytic tools for the incorporation of unusual features
      compared with the ribosomal system. Several crystal structures of NRPS-domains
      have yielded deep insight into the catalytic mechanisms involved and have led to
      a better prediction of the products assembled and to the construction of hybrid
      enzymes. In addition to the structure-function relationship of the core- and
      tailoring-domains of NRPSs, which is the main focus of this review, different
      biosynthetic strategies and essential enzymes for posttranslational modification
      and editing are discussed.

PMID- 15487946
TI  - Circadian rhythms in microorganisms: new complexities.
AB  - Recent advances in understanding circadian (daily) rhythms in the genera
      Neurospora, Gonyaulax, and Synechococcus are reviewed and new complexities in
      their circadian systems are described. The previous model, consisting of a
      unidirectional flow of information from input to oscillator to output, has now
      expanded to include multiple input pathways, multiple oscillators, multiple
      outputs; and feedback from oscillator to input and output to oscillator. New
      posttranscriptional features of the frq/white-collar oscillator (FWC) of
      Neurospora are described, including protein phosphorylation and degradation,
      dimerization, and complex formation. Experimental evidence is presented for frq
      less oscillator(s) (FLO) downstream of the FWC. Mathematical models of the
      Neurospora system are also discussed.

PMID- 15487947
TI  - The cellulosomes: multienzyme machines for degradation of plant cell wall
      polysaccharides.
AB  - The discrete multicomponent, multienzyme cellulosome complex of anaerobic
      cellulolytic bacteria provides enhanced synergistic activity among the different
      resident enzymes to efficiently hydrolyze intractable cellulosic and
      hemicellulosic substrates of the plant cell wall. A pivotal noncatalytic subunit
      called scaffoldin secures the various enzymatic subunits into the complex via the
      cohesin-dockerin interaction. The specificity characteristics and tenacious
      binding between the scaffoldin-based cohesin modules and the enzyme-borne
      dockerin domains dictate the supramolecular architecture of the cellulosome. The
      diversity in cellulosome architecture among the known cellulosome-producing
      bacteria is manifest in the arrangement of their genes in either multiple
      scaffoldin or enzyme-linked clusters on the genome. The recently described three
      dimensional crystal structure of the cohesin-dockerin heterodimer sheds light on
      the critical amino acids that contribute to this high-affinity protein-protein
      interaction. In addition, new information regarding the regulation of cellulosome
      related genes, budding genetic tools, and emerging genomics of cellulosome
      producing bacteria promises new insight into the assembly and consequences of the
      multienzyme complex.

PMID- 15487948
TI  - Biophysical analyses of designed and selected mutants of protocatechuate 3,4
      dioxygenase1.
AB  - The catechol dioxygenases allow a wide variety of bacteria to use aromatic
      compounds as carbon sources by catalyzing the key ring-opening step. These
      enzymes use specifically either catechol or protocatechuate (2,3
      dihydroxybenozate) as their substrates; they use a bare metal ion as the sole
      cofactor. To learn how this family of metalloenzymes functions, a structural
      analysis of designed and selected mutants of these enzymes has been undertaken.
      Here we review the results of this analysis on the nonheme ferric iron intradiol
      dioxygenase protocatechuate 3,4-dioxygenase.

PMID- 15487949
TI  - Molecular determinants of Listeria monocytogenes virulence.
AB  - Listeria monocytogenes is the etiological agent of listeriosis, a severe human
      foodborne infection characterized by gastroenteritis, meningitis, encephalitis,
      abortions, and perinatal infections. This gram-positive bacterium is a
      facultative intracellular pathogen that induces its own uptake into nonphagocytic
      cells and spreads from cell to cell using an actin-based motility process. This
      review covers both well-established and recent advances in the characterization
      of L. monocytogenes virulence determinants and their role in the pathophysiology
      of listeriosis.

PMID- 15487950
TI  - Bacterial iron sources: from siderophores to hemophores.
AB  - Iron is an essential element for most organisms, including bacteria. The oxidized
      form is insoluble, and the reduced form is highly toxic for most macromolecules
      and, in biological systems, is generally sequestrated by iron- and heme-carrier
      proteins. Thus, despite its abundance on earth, there is practically no free iron
      available for bacteria whatever biotope they colonize. To fulfill their iron
      needs, bacteria have multiple iron acquisition systems, reflecting the diversity
      of their potential biotopes. The iron/heme acquisition systems in bacteria have
      one of two general mechanisms. The first involves direct contact between the
      bacterium and the exogenous iron/heme sources. The second mechanism relies on
      molecules (siderophores and hemophores) synthesized and released by bacteria into
      the extracellular medium; these molecules scavenge iron or heme from various
      sources. Recent genetic, biochemical, and crystallographic studies have allowed
      substantial progress in describing molecular mechanisms of siderophore and
      hemophore interactions with the outer membrane receptors, transport through the
      inner membrane, iron storage, and regulation of genes encoding biosynthesis and
      uptake proteins.

PMID- 15487951
TI  - Endangered antarctic environments.
AB  - The Antarctic continent harbors a range of specialized and sometimes highly
      localized microbial biotopes. These include biotopes associated with desiccated
      mineral soils, rich ornithogenic soils, glacial and sea ice, ice-covered lakes,
      translucent rocks, and geothermally heated soils. All are characterized by the
      imposition of one or more environmental extremes (including low temperature, wide
      temperature fluctuations, desiccation, hypersalinity, high periodic radiation
      fluxes, and low nutrient status). As our understanding of the true microbial
      diversity in these biotopes expands from the application of molecular
      phylogenetic methods, we come closer to the point where we can make an accurate
      assessment of the impacts of environmental change, human intervention, and other
      natural and unnatural impositions. At present, it is possible to make reasonable
      predictions about the physical effects of local climate change, but only general
      predictions on possible changes in microbial community structure. The
      consequences of some direct human impacts, such as physical disruption of
      microbial soil communities, are obvious if not yet quantitated. Others, such as
      the dissemination of nonindigenous microorganisms into indigenous microbial
      communities, are not yet understood.

PMID- 15487952
TI  - Testosterone prescribing in Australia.
AB  - There is yet no convincing evidence that testosterone therapy is safe or
      effective in counteracting any effects of ageing.

PMID- 15487953
TI  - Maternal deaths in Australia, 1997-1999.
AB  - Many maternal deaths in Australia are still preventable.

PMID- 15487954
TI  - Human papillomavirus: a cause of some head and neck cancers?
AB  - Establishing a causal link between HPV and certain head and neck cancers would
      have implications for prognosis, prevention and therapy.

PMID- 15487955
TI  - Lying awake worrying about asteroids.

PMID- 15487956
TI  - Trends and regional differences in testosterone prescribing in Australia, 1991
      2001.
AB  - OBJECTIVES: To analyse temporal trends and geographical variations in
      testosterone prescribing in Australia. DESIGN AND SETTING: An analysis of
      testosterone prescribing over the past 11 years according to products and region,
      determined by Pharmaceutical Benefits Scheme (PBS) expenditure in Australian
      states and territories. MAIN OUTCOME MEASURE: Patterns of monthly PBS expenditure
      on injectable, oral and implantable testosterone products from 1 January 1991 to
      30 December 2001, classified by state or territory. RESULTS: There were two
      periods (1993-1994 and 1998-1999) of striking upsurge followed by declines in
      national total prescribing of testosterone. These changes were more prominent for
      oral than injectable testosterone products, and patterns were similar in all
      regions, apart from a disproportionately higher peak in Western Australia in
      1998. On a per-capita basis, Western Australia showed a dramatic increase in
      prescribing of oral and implantable, but not injectable, testosterone coinciding
      with the opening of a franchised men's sexual health clinic in Perth. CONCLUSION:
      The two striking upsurges in testosterone prescribing despite no convincing new
      evidence to justify them appear to reflect promotional activity to prescribe
      testosterone for older men, rather than overcoming the underdiagnosis of androgen
      deficiency related to pituitary or testicular disease in younger men. The
      curtailments after the introduced restrictions to PBS prescribing for older men
      without overt androgen deficiency were partial and temporary, suggesting that
      such regulatory barriers are only partly successful in counteracting the
      commercial and populist pressure driving excessive testosterone prescribing.
      Professional and community education is needed for appropriate diagnosis of
      genuine androgen deficiency in younger men, while discouraging unproven
      testosterone treatment for ageing men.

PMID- 15487957
TI  - Colonoscopy screening for colorectal cancer: the outcomes of two recruitment
      methods.
AB  - OBJECTIVES: To determine the response to colorectal cancer (CRC) screening by
      colonoscopy, through direct invitation or through invitation by general
      practitioners. DESIGN AND SETTING: Two-way comparison of randomised population
      sampling versus cluster sampling of a representative general practice population
      in the Australian Capital Territory, May 2002 to January 2004. INTERVENTION:
      Invitation to screen, assessment for eligibility, interview, and colonoscopy.
      SUBJECTS: 881 subjects aged 55-74 years were invited to screen: 520 from the
      electoral roll (ER) sample and 361 from the general practice (GP) cluster sample.
      MAIN OUTCOME MEASURES: Response rate, participation rate, and rate of adenomatous
      polyps in the screened group. RESULTS: Participation was similar in the ER arm
      (35.1%; 95% CI, 30.2%-40.3%) and the GP arm (40.1%; 95% CI, 29.2%-51.0%) after
      correcting for ineligibility, which was higher in the ER arm. Superior
      eligibility in the GP arm was offset by the labour of manual record review.
      Response rates after two invitations were similar for the two groups (ER arm:
      78.8%; 95% CI, 75.1%-82.1%; GP arm: 81.7%; 95% CI, 73.8%-89.6%). Overall, 53.4%
      ineligibility arose from having a colonoscopy in the past 10 years (ER arm,
      98/178; GP arm, 42/84). Of 231 colonoscopies performed, 229 were complete, with
      32% of subjects screened having adenomatous polyps. CONCLUSIONS: Colonoscopy
      based CRC screening yields similar response and participation rates with either
      random population sampling or general practice cluster sampling, with population
      sampling through the electoral roll providing greater ease of recruitment.

PMID- 15487958
TI  - Using checklists and reminders in clinical pathways to improve hospital inpatient
      care.
AB  - OBJECTIVES: To determine whether the quality of hospital inpatient care can be
      improved by using checklists and reminders in clinical pathways. DESIGN:
      Comparison of key indicators before and after the introduction of clinical
      pathways incorporating daily checklists and reminders of best practice integrated
      into patient medical records. SETTING AND PARTICIPANTS: The study, at Wimmera
      Base Hospital in Horsham, Victoria, included patients admitted between 1 January
      1999 and 31 December 2002 with ST-elevation acute myocardial infarction (AMI) and
      patients admitted between 31 July 1999 and 31 December 2002 with stroke. MAIN
      OUTCOME MEASURES: Compliance with key process measures determined as best
      practice for each clinical pathway. RESULTS: 116 patients with AMI and 123
      patients with stroke were included in the study. ST-elevation AMI. After
      introducing the clinical pathway program, percentage-point increases for
      treatment compliance were 21.4% (95% CI, 7.3%-32.7%) for patients receiving
      aspirin in the emergency department; 42.7% (95% CI, 26.3%-59.0%) for eligible
      patients receiving beta-blockers within 24 h of admission; 48.1% (95% CI, 31.4%
      64.8%) for eligible patients being prescribed beta-blockers on discharge; 43.7%
      (95% CI, 28.4%-59.1%) for patients having fasting lipid levels measured; and
      41.2% (95% CI, 19.0%-63.5%) for eligible patients having lipid therapy. Stroke.
      After introducing the clinical pathway program, percentage-point increases for
      treatment compliance were 40.7% (95% CI, 21.0%-60.2%) for dysphagia screening
      within 24 h of admission; 55.4% (95% CI, 32.9%-77.9%) for patients with ischaemic
      stroke receiving aspirin or clopidogrel within 24 h of admission; and 52.4% (95%
      CI, 33.8%-70.9%) for patients having regular neurological observations during the
      first 48 h after a stroke. There was a fall of 1.0 percentage point (ie, a
      difference of -1% [95% CI, -4.7% to 10.0%]) in the proportion of patients having
      a computed tomography brain scan within 24 h of admission. CONCLUSION:
      Significant improvements in the quality of patient care can be achieved by
      incorporating checklists and reminders into clinical pathways.

PMID- 15487959
TI  - The direct thrombin inhibitor melagatran/ximelagatran.
AB  - Melagatran is a synthetic, small-peptide direct thrombin inhibitor with
      anticoagulant activity. Ximelagatran, an oral prodrug, undergoes rapid enzymatic
      conversion to melagatran. Melagatran has rapid onset of action, fixed twice-daily
      dosing, stable absorption, apparent low potential for medication interactions,
      and no requirement for monitoring drug levels or dose adjustment. There is no
      specific antidote, but the drug has a short plasma elimination half-life (about 4
      hours). In clinical studies, melagatran/ximelagatran is not inferior to warfarin
      for stroke prevention in patients with non-valvular atrial fibrillation, to
      heparin-warfarin for acute treatment and extended secondary prevention of deep
      vein thrombosis, and superior to warfarin for prevention of venous
      thromboembolism after major orthopaedic surgery. Major bleeding with
      melagatran/ximelagatran occurred at rates similar to those in patients treated
      with warfarin. 6%-12% of patients taking ximelagatran develop asymptomatic
      elevated liver enzyme levels (predominantly alanine aminotransferase) after 1-6
      months of therapy; this usually resolves with cessation of therapy. Less than 1%
      of patients develop abnormal liver function while taking ximelagatran; this
      rarely persists or develops into clinical illness.

PMID- 15487961
TI  - Throwing out the baby with the spa water?
AB  - Australia is now one of the safest countries in the world in which to be born.
      This is largely a result of the many advances in obstetric and neonatal medicine
      of the past 50 years. However, the "medicalisation" of birth has tended to
      diminish women's satisfaction with their experience of childbirth. It has been
      shown that women are most satisfied by care from a single practitioner, and when
      they themselves have input into decision-making. Although maternal satisfaction
      is important, it should not be promoted at the expense of the health of mothers
      and babies. More realistic antenatal education and preparation should be
      available for all pregnant women so that both maternal satisfaction and good
      perinatal outcomes can be achieved.

PMID- 15487962
TI  - Research ethics committees: what is their contribution?

PMID- 15487963
TI  - Gardner; re BWV: Victorian Supreme Court makes landmark Australian ruling on tube
      feeding.
AB  - The Victorian Supreme Court has decided that artificial nutrition and hydration
      provided through a percutaneous gastrostomy tube to a woman in a persistent
      vegetative state may be withdrawn. The judge ruled, in line with a substantial
      body of international medical, ethical and legal opinion, that any form of
      artificial nutrition and hydration is a medical procedure, not part of palliative
      care, and that it is a procedure to sustain life, not to manage the dying
      process. Thus, the law does not impose a rigid obligation to administer
      artificial nutrition or hydration to people who are dying, without due regard to
      their clinical condition. The definition of key terms such as "medical
      treatment", "palliative care", and "reasonable provision of food and water" in
      this case will serve as guidance for end-of-life decisions in other states and
      territories. The case also reiterates the right of patients, and, when
      incompetent, their validly appointed agents or guardians, to refuse medical
      treatment. Where an incompetent patient has not executed a binding advance
      directive and no agent or guardian has been appointed, physicians, in
      consultation with the family, may decide to withdraw medical treatment, including
      artificial nutrition or hydration, on the basis that continuation of treatment is
      inappropriate and not in the patient's best interests. However, Victoria and
      other jurisdictions would benefit from clarification of this area of the law.

PMID- 15487964
TI  - Visceral leishmaniasis: a trip to the Greek Islands is not always idyllic.
AB  - Although cutaneous leishmaniasis is occasionally seen in Australia in overseas
      travellers and migrants, visceral leishmaniasis has been reported rarely and only
      in people who were immunocompromised. We describe an 18-year-old immunocompetent
      man who presented with pancytopenia and a 2-week history of fever and lethargy a
      year after visiting the Greek Islands. Visceral leishmaniasis was diagnosed after
      a bone marrow biopsy showed protozoa, and the patient responded well to treatment
      with liposomal amphotericin. To our knowledge, this is the first case of visceral
      leishmaniasis in an immunocompetent patient in Australia.

PMID- 15487965
TI  - Combined treatment with angiotensin-converting enzyme inhibitors and angiotensin
      receptor blockers to prevent end-stage kidney disease in patients who do not have
      diabetes.

PMID- 15487966
TI  - Multiple analyses in clinical trials: sound science or data dredging?

PMID- 15487967
TI  - Subsidised access to TNF alpha inhibitors: is the rationale for exclusion of
      rheumatoid-factor-negative patients defensible?

PMID- 15487968
TI  - The medical profession and the pharmaceutical industry: when will we open our
      eyes?

PMID- 15487969
TI  - Multicentre research: negotiating the ethics approval obstacle course.

PMID- 15487970
TI  - Management of obesity.

PMID- 15487971
TI  - Thyroid testing 10 years on.

PMID- 15487972
TI  - Preventing intrathecal administration of vincristine.

PMID- 15487973
TI  - The Drosophila protein kinase LK6 is regulated by ERK and phosphorylates the
      eukaryotic initiation factor eIF4E in vivo.
AB  - In Drosophila cells, phosphorylation of eIF4E (eukaryotic initiation factor 4E)
      is required for growth and development. In Drosophila melanogaster, LK6 is the
      closest homologue of mammalian Mnk1 and Mnk2 [MAPK (mitogen-activated protein
      kinase) signal-integrating kinases 1 and 2 respectively] that phosphorylate
      mammalian eIF4E. Mnk1 is activated by both mitogen- and stress-activated
      signalling pathways [ERK (extracellular-signal-regulated kinase) and p38 MAPK],
      whereas Mnk2 contains a MAPK-binding motif that is selective for ERKs. LK6
      possesses a binding motif similar to that in Mnk2. In the present study, we show
      that LK6 can phosphorylate eIF4E at the physiological site. LK6 activity is
      increased by the ERK signalling pathway and not by the stress-activated p38 MAPK
      signalling pathway. Consistent with this, LK6 binds ERK in mammalian cells, and
      this requires an intact binding motif. LK6 can bind to eIF4G in mammalian cells,
      and expression of LK6 increases the phosphorylation of the endogenous eIF4E. In
      Drosophila S2 Schneider cells, LK6 binds the ERK homologue Rolled, but not the
      p38 MAPK homologue. LK6 phosphorylates Drosophila eIF4E in vitro. The
      phosphorylation of endogenous eIF4E in Drosophila cells is increased by
      activation of the ERK pathway but not by arsenite, an activator of p38 MAPK. RNA
      interference directed against LK6 significantly decreases eIF4E phosphorylation
      in Drosophila cells. These results show that LK6 binds to ERK and is activated by
      ERK signalling and it is responsible for phosphorylating eIF4E in Drosophila.

PMID- 15487974
TI  - Anomalous pH-dependence of the activity of human matrilysin (matrix
      metalloproteinase-7) as revealed by nitration and amination of its tyrosine
      residues.
AB  - Matrilysin activity exhibits a broad bell-shaped pH-dependence profile, with
      pK(a) values of 4.0 and 9.8. A maximum of five out of eight tyrosine residues in
      matrilysin were nitrated with tetranitromethane. On nitration of between one and
      five tyrosines, pK(a) at the alkaline side (pK(e2)) was shifted from 9.8 to 10.3
      10.6, while that at the acidic side (pK(e1)) was not altered. The pK(e2) that was
      shifted by nitration to 10.3-10.6 was restored to 9.4-9.7 by subsequent
      amination, suggesting that the shift in pK(e2) is induced by a negative charge
      introduced on the most reactive tyrosine, Tyr-150. The Michaelis constant (K(m))
      observed at pH 10 was decreased by nitration as a result of the increase in
      pK(e2), suggesting that the residue with pK(e2) may play a role in the
      recognition of substrate. When four or five tyrosines were nitrated, the activity
      at pH <7 decreased significantly, while that at pH 7-10 was unchanged, and thus
      the pH-dependence was not bell-shaped, but anomalous, with a third pK(a) (pK(e3))
      of 6.2-6.4 in addition to pK(e1) and pK(e2). This suggests the possibility that a
      newly introduced nitrotyrosine residue has a strong influence on the activity as
      an ionizable group.

PMID- 15487975
TI  - Cross-sectional study of complement C3 as a coronary risk factor among men and
      women.
AB  - In the present study, we examined (i) whether C3 (complement C3) was an
      independent marker of prevalent CHD (coronary heart disease), and (ii) which
      preferential associations existed between C3 and some cardiovascular risk factors
      when jointly analysed with CRP (C-reactive protein) and fibrinogen. In a cohort
      of 756 unselected adults, 39% of whom had the metabolic syndrome, C3 and other
      risk variables were evaluated in a cross-sectional manner. In a logistic
      regression model for the likelihood of CHD, a significant OR (odds ratio) of 3.5
      [95% CI (confidence intervals), 1.27 and 9.62)] for C3 was obtained after
      adjustment for smoking status, TC (total cholesterol) and usage of statins. A
      similar model, also comprising systolic blood pressure, with a cut-off point of
      >or=1.6 g/l C3 exhibited a 1.9-fold risk (95% CI, 1.01 and 3.58) compared with
      individuals below the cut-off point. Both analyses displayed an adjusted OR of
      1.37 for each S.D. increment in C3. The significant relationship of C3 with a
      likelihood of CHD also proved to be independent of CRP. In multiple linear
      regression models, associations were tested for each acute-phase protein with
      measures of obesity, fasting insulin, triacylglycerols (triglycerides), TC, HDL
      (high-density lipoprotein)-cholesterol, physical activity, smoking status,
      diagnosis of metabolic syndrome and family income. When both genders were
      combined, C3 was independently associated with serum triacylglycerols, waist
      circumference, BMI (body mass index) and TC. CRP was independently associated
      with waist circumference, TC, family income (inversely) and physical activity,
      and fibrinogen with BMI, TC, smoking status and metabolic syndrome. In summary,
      elevated levels of complement C3 are associated with an increased likelihood of
      CHD independent of standard risk factors and regardless of the presence of acute
      coronary events, suggesting that C3 might be actively involved in coronary
      atherothrombosis. Unlike CRP and fibrinogen, C3 was preferentially associated
      with waist girth and serum triacylglycerols.

PMID- 15487977
TI  - Treating to goal: challenges of current management.
AB  - Extensive evidence supports the benefits of treating to glycated haemoglobin
      (HbA1c) goal, both in terms of health and economic outcomes. As shown by the UK
      Prospective Diabetes Study (UKPDS) and the Diabetes Control and Complications
      Trial (DCCT), the risk of patients with type 2 diabetes developing vascular
      complications is strongly correlated with HbA1c levels and the duration of poor
      glycaemic control. Moreover, good glycaemic control significantly reduces the
      risk of complications. In controlled clinical trials, a number of pharmacological
      agents have been shown to significantly reduce HbA1c levels in patients with type
      2 diabetes. However, the reality is that most patients with type 2 diabetes have
      HbA1c levels above the recommended target levels. Although there are regional
      differences in the average HbA1c level, poor glycaemic control is a universal
      problem that will continue to grow in line with the rapidly increasing prevalence
      of type 2 diabetes. Barriers to good blood glucose control are present in almost
      every aspect of diabetes care. Furthermore, in patients with type 2 diabetes,
      therapy-, patient- and/or healthcare system-related barriers are compounded by an
      ongoing decline in beta-cell function that is characteristic of the progressive
      nature of the disease. Therapy-related barriers include reduced long-term
      efficacy with oral agents, fear of hypoglycaemia and a variety of issues related
      to flexibility and convenience that encourage poor compliance with therapy. From
      the patient perspective, issues relating to lifestyle, education, psychology and
      the environment can prevent optimum diabetes self-management. Poor access to
      and/or use of specialist healthcare resources also has a negative effect on
      treatment outcomes. These barriers to glycaemic control need to be overcome so
      that the established benefits of reducing glucose to normal or near-normal levels
      can be experienced by more people with type 2 diabetes.

PMID- 15487978
TI  - Resourcing issues.
AB  - Diabetes is a chronic, progressive disease and achieving appropriate control of
      glycaemia and the other associated cardiovascular risk factors is essential to
      prevent its long-term complications. Currently, recovery and rehabilitation from
      the cardiovascular complications of diabetes are the major focus of diabetes care
      rather than primary and secondary prevention of diabetes and its complications.
      This focus, coupled with limited funding and other resource issues, means that
      diabetes care and outcomes are generally suboptimal. More efficient and effective
      management strategies, primarily based upon a broad educational approach
      including both those with diabetes and their care-givers will be essential in
      reducing the cost of diabetes and diabetes-related complications. Continuous
      education of patients and providers increases the quality of care and improves
      clinical and metabolic outcomes as well as reducing the cost of care and
      optimising human and financial resources. Thus, education will be a key strategy
      in minimising the growing burden of diabetes on society. Making these changes
      will require the co-operation of patients, their families, the community,
      healthcare policy makers, national governments and the pharmaceutical industry.
      Medical schools must also place more emphasis on educating doctors about chronic
      disease management using not only recovery and rehabilitation, but also
      prevention strategies, emphasising the importance of helping patients to
      participate in the control of their disease.

PMID- 15487979
TI  - Psychological barriers.
AB  - Type 2 diabetes treatment outcomes ultimately depend on patients and their
      ability to make long-term behavioural changes that support good self-care and
      metabolic control. Patients' perceptions about diabetes and diabetes-related
      complications can have a strong influence on their emotional well-being, as well
      as day-to-day self-care and the quality of metabolic control. The gravity of
      diabetes is often underestimated, and many patients do not understand the link
      between poor glycaemic control and long-term complications of the disease.
      Similarly, people with diabetes commonly undervalue the role of lifestyle changes
      and pharmacological therapy in preventing future complications. Negative emotions
      and preconceptions about treatment can also discourage adherence to treatment
      plans. 'Psychological insulin resistance' caused by fear and concerns about
      insulin and daily insulin injections can discourage many patients from starting
      insulin therapy, even if oral agents have failed. Depression, stress and anxiety
      represent further obstacles to optimum self-care and the attainment of glucose
      goals. Healthcare professionals should endeavour to understand and accommodate
      these issues when setting personal treatment goals and developing plans to
      achieve them. Importantly, the advice and support they provide should be tailored
      to the unique needs of each patient. There is scope to improve outpatient
      consultations to ensure agreement between patients and professionals concerning
      issues discussed and decisions made, and this may help to improve recall and
      motivation to manage diabetes. Engaging patients in the goal-setting process can
      help to overcome potential barriers to good self-care and may increase the
      probability that treatment goals are achieved.

PMID- 15487980
TI  - Overcoming obstacles: collaboration for change.
AB  - Effective diabetes care requires a partnership between prepared, proactive
      practice teams and informed, activated patients. Diabetes education helps to
      overcome many of the barriers to effective self-management by enabling people
      with diabetes to make informed decisions about their day-to-day self-care. Both
      psychosocial and health outcomes have been improved through a variety of training
      programmes; however, education must be coupled with ongoing self-management
      support if these benefits are to be sustained. The principal goal of diabetes
      education has undergone a major shift over the past few years--evolving from
      primarily didactic interventions, focused on encouraging patients to adhere to
      the prescribed therapy, towards more interactive learning that supports people in
      making informed, self-directed decisions.

PMID- 15487981
TI  - Overcoming obstacles: new management options.
AB  - The outlook for patients with type 2 diabetes looks set to improve with the
      availability of new diabetes management options that provide more comprehensive
      control of blood glucose levels and/or encourage better patient compliance than
      previous alternatives. New insulin analogues, such as insulin lispro, aspart and
      glargine, allow more physiological insulin replacement and greater freedom in the
      timing and content of meals, compared with regular insulin preparations. The
      development of novel non-invasive routes of insulin administration promises to
      further improve diabetes management. Many barriers to initiating insulin relate
      to the need for frequent insulin injections, fears that insulin injections will
      be painful and difficult to administer, and concerns about hypoglycaemia and
      weight gain. Thus, each measure that reduces these barriers will help to prevent
      inappropriate delays in starting insulin therapy as well as to promote better
      compliance with therapy. The output from continuous glucose monitoring devices
      will assist accurate insulin replacement, which is difficult using point
      estimates of blood glucose. Such devices will hopefully also circumvent the need
      for finger stick tests. There are several novel therapies in development that
      will further expand the portfolio of treatment options for patients with type 2
      diabetes. Improved quality and choice of diabetes management options will provide
      doctors with the tools they require to develop tailored treatment plans, increase
      the probability that treatment goals are achieved and thereby reduce the risk of
      patients developing late-stage diabetes-related complications.

PMID- 15487983
TI  - Mapping residues of SUMO precursors essential in differential maturation by SUMO
      specific protease, SENP1.
AB  - SUMO (small ubiquitin-related modifier) is a member of the ubiquitin-like protein
      family that regulates cellular function of a variety of target proteins. SUMO
      proteins are expressed as their precursor forms. Cleavage of the residues after
      the 'GG' region of these precursors by SUMO-specific proteases in maturation is a
      prerequisite for subsequent sumoylation. To understand further this proteolytic
      processing, we expressed and purified SENP1 (sentrin-specific protease 1), one of
      the SUMO-specific proteases, using an Escherichia coli expression system. We show
      that SENP1 is capable of processing all SUMO-1, -2 and -3 in vitro; however, the
      proteolytic efficiency of SUMO-1 is the highest followed by SUMO-2 and -3. We
      demonstrate further that the catalytic domain of SENP1 (SENP1C) alone can
      determine the substrate specificity towards SUMO-1, -2 and -3. Replacement of the
      C-terminal fragments after the 'GG' region of SUMO-1 and -2 precursors with that
      of the SUMO-3, indicates that the C-terminal fragment is essential for efficient
      maturation. In mutagenesis analysis, we further map two residues immediately
      after the 'GG' region, which determine the differential maturation. Distinct
      patterns of tissue distribution of SENP1, SUMO-1, -2 and -3 are characterized.
      Taken together, we suggest that the observed differential maturation process has
      its physiological significance in the regulation of the sumoylation pathway.

PMID- 15487984
TI  - Kinetic investigation of human dipeptidyl peptidase II (DPPII)-mediated
      hydrolysis of dipeptide derivatives and its identification as quiescent cell
      proline dipeptidase (QPP)/dipeptidyl peptidase 7 (DPP7).
AB  - The presence of DPPII (dipeptidyl peptidase II; E.C. 3.4.14.2) has been
      demonstrated in various mammalian tissues. However, a profound molecular and
      catalytic characterization, including substrate selectivity, kinetics and pH
      dependence, has not been conducted. In the present study, DPPII was purified from
      human seminal plasma to apparent homogeneity with a high yield (40%) purification
      scheme, including an inhibitor-based affinity chromatographic step. The inhibitor
      lysyl-piperidide (K(i) approximately 0.9 microM at pH 5.5) was chosen, as it
      provided a favourable affinity/recovery ratio. The human enzyme appeared as a 120
      kDa homodimer. Mass spectrometric analysis after tryptic digestion together with
      a kinetic comparison indicate strongly its identity with QPP (quiescent cell
      proline dipeptidase), also called dipeptidyl peptidase 7. pH profiles of both
      kcat and kcat/K(m) clearly demonstrated that DPPII/QPP possesses an acidic and
      not a neutral optimum as was reported for QPP. Kinetic parameters of the human
      natural DPPII for dipeptide-derived chromogenic [pNA (p-nitroanilide)] and
      fluorogenic [4Me2NA (4-methoxy-2-naphthylamide)] substrates were determined under
      different assay conditions. DPPII preferred the chromogenic pNA-derived
      substrates over the fluorogenic 4Me2NA-derived substrates. Natural human DPPII
      showed high efficiency towards synthetic substrates containing proline at the P1
      position and lysine at P2. The importance of the P1' group for P2 and P1
      selectivity was revealed, explaining many discrepancies in the literature.
      Furthermore, substrate preferences of human DPPII and dipeptidyl peptidase IV
      were compared based on their selectivity constants (kcat/K(m)). Lys-Pro-pNA
      (k(cat)/K(m) 4.1x10(6) s(-1) x M(-1)) and Ala-Pro-pNA (kcat/K(m) 2.6x10(6) s(-1)
      x M(-1)) were found to be the most sensitive chromogenic substrates for human
      DPPII, but were less selective than Lys-Ala-pNA (kcat/K(m) 0.4x10(6) s(-1) x M(
      1)).

PMID- 15487985
TI  - Genomic organization of human arylamine N-acetyltransferase Type I reveals
      alternative promoters that generate different 5'-UTR splice variants with altered
      translational activities.
AB  - In humans, a polymorphic gene encodes the drug-metabolizing enzyme NAT1
      (arylamine N-acetyltransferase Type 1), which is widely expressed throughout the
      body. While the protein-coding region of NAT1 is contained within a single exon,
      examination of the human EST (expressed sequence tag) database at the NCBI
      revealed the presence of nine separate exons, eight of which were located in the
      5' non-coding region of NAT1. Differential splicing produced at least eight
      unique mRNA isoforms that could be grouped according to the location of the first
      exon, which suggested that NAT1 expression occurs from three alternative
      promoters. Using RT (reverse transcriptase)-PCR, we identified one major
      transcript in various epithelial cells derived from different tissues. In
      contrast, multiple transcripts were observed in blood-derived cell lines (CEM,
      THP-1 and Jurkat), with a novel variant, not identified in the EST database,
      found in CEM cells only. The major splice variant increased gene expression 9-11
      fold in a luciferase reporter assay, while the other isoforms were similar or
      slightly greater than the control. We examined the upstream region of the most
      active splice variant in a promoter-reporter assay, and isolated a 257 bp
      sequence that produced maximal promoter activity. This sequence lacked a TATA
      box, but contained a consensus Sp1 site and a CAAT box, as well as several other
      putative transcription-factor-binding sites. Cell-specific expression of the
      different NAT1 transcripts may contribute to the variation in NAT1 activity in
      vivo.

PMID- 15487986
TI  - The interaction of carbohydrate-binding modules with insoluble non-crystalline
      cellulose is enthalpically driven.
AB  - Natural cellulose exists as a composite of cellulose forms, which can be broadly
      characterized as crystalline or non-crystalline. The recognition of both of these
      forms of cellulose by the CBMs (carbohydrate-binding modules) of microbial
      glycoside hydrolases is important for the efficient natural and biotechnological
      conversion of cellulosic biomass. The category of CBM that binds insoluble non
      crystalline cellulose does so with an affinity approx. 10-20-fold greater than
      their affinity for cello-oligosaccharides and/or soluble polysaccharides. This
      phenomenon has been assumed to originate from the effects of changes in
      configurational entropy upon binding. The loss of configurational entropy is
      thought to be less profound upon binding to conformationally restrained insoluble
      non-crystalline cellulose, resulting in larger free energies of binding. However,
      using isothermal titration calorimetry, it is shown that this is not the case for
      the high-affinity interactions of CcCBM17 (the family 17 CBM from EngF of
      Clostridium cellulovorans) and BspCBM28 (the family 28 CBM from Cel5A of Bacillus
      species 1139) with regenerated cellulose, an insoluble preparation of primarily
      non-crystalline cellulose. The enhanced free energy of binding of non-crystalline
      cellulose relative to cello-oligosaccharides is by virtue of improved enthalpy,
      not entropy.

PMID- 15487987
TI  - How to track and assess genotyping errors in population genetics studies.
AB  - Genotyping errors occur when the genotype determined after molecular analysis
      does not correspond to the real genotype of the individual under consideration.
      Virtually every genetic data set includes some erroneous genotypes, but
      genotyping errors remain a taboo subject in population genetics, even though they
      might greatly bias the final conclusions, especially for studies based on
      individual identification. Here, we consider four case studies representing a
      large variety of population genetics investigations differing in their sampling
      strategies (noninvasive or traditional), in the type of organism studied (plant
      or animal) and the molecular markers used [microsatellites or amplified fragment
      length polymorphisms (AFLPs)]. In these data sets, the estimated genotyping error
      rate ranges from 0.8% for microsatellite loci from bear tissues to 2.6% for AFLP
      loci from dwarf birch leaves. Main sources of errors were allelic dropouts for
      microsatellites and differences in peak intensities for AFLPs, but in both cases
      human factors were non-negligible error generators. Therefore, tracking
      genotyping errors and identifying their causes are necessary to clean up the data
      sets and validate the final results according to the precision required. In
      addition, we propose the outline of a protocol designed to limit and quantify
      genotyping errors at each step of the genotyping process. In particular, we
      recommend (i) several efficient precautions to prevent contaminations and
      technical artefacts; (ii) systematic use of blind samples and automation; (iii)
      experience and rigor for laboratory work and scoring; and (iv) systematic
      reporting of the error rate in population genetics studies.

PMID- 15487988
TI  - Population structure of the large Japanese field mouse, Apodemus speciosus
      (Rodentia: Muridae), in suburban landscape, based on mitochondrial D-loop
      sequences.
AB  - Genetic structure of the large Japanese field mouse populations in suburban
      landscape of West Tokyo, Japan was determined using mitochondrial DNA control
      region sequence. Samples were collected from six habitats linked by forests and
      green tract along the Tama River, and from two forests segregated by urban areas
      from those continuous habitats. Thirty-five haplotypes were detected in 221
      animals. Four to eight haplotypes were found within each local population
      belonging to the continuous landscape. Some haplotypes were shared by two or
      three adjacent local populations. On the other hand, two isolated habitats were
      occupied by one or two indigenous haplotypes. Significant genetic differentiation
      between all pairs of local populations, except for one pair in the continuous
      habitats, was found by analysis of molecular variance (amova). The geographical
      distance between habitats did not explain the large variance of pairwise F(ST)
      values among local populations. F(ST)-values between local populations segregated
      by urban areas were higher than those between local populations in the continuous
      habitat, regardless of geographical distance. The results of this study
      demonstrated quantitatively that urban areas inhibit the migration of Apodemus
      speciosus, whereas a linear green tract along a river functions as a corridor.
      Moreover, it preserves the metapopulation structure of A. speciosus as well as
      the corridors in suburban landscape.

PMID- 15487989
TI  - Estimation of genetically effective breeding numbers using a rejection algorithm
      approach.
AB  - Polygynous mating results in nonrandom sampling of the adult male gamete pool in
      each generation, thereby increasing the rate of genetic drift. In principle,
      genetic paternity analysis can be used to infer the effective number of breeding
      males (Nebm). However, this requires genetic data from an exhaustive sample of
      candidate males. Here we describe a new approach to estimate Nebm using a
      rejection algorithm in association with three statistics: Euclidean distance
      between the frequency distributions of maternally and paternally inherited
      alleles, average number of paternally inherited alleles and average gene
      diversity of paternally inherited alleles. We quantify the relationship between
      these statistics and Nebm using an individual-based simulation model in which the
      male mating system varied continuously between random mating and extreme
      polygyny. We evaluate this method using genetic data from a natural population of
      highly polygynous fruit bats (Cynopterous sphinx). Using data in the form of
      mother-offspring genotypes, we demonstrate that estimates of Nebm are very
      similar to independent estimates based on a direct paternity analysis that
      included data on candidate males. Our method also permits an evaluation of
      uncertainty in estimates of Nebm and thus facilitates inferences about the mating
      system from genetic data. Finally, we investigate the sensitivity of our method
      to sample size, model assumptions, adult population size and the mating system.
      These analyses demonstrate that the rejection algorithm provides accurate
      estimates of Nebm across a broad range of demographic scenarios, except when the
      true Nebm is high.

PMID- 15487990
TI  - Genetic structuring of Patagonian toothfish populations in the Southwest Atlantic
      Ocean: the effect of the Antarctic Polar Front and deep-water troughs as barriers
      to genetic exchange.
AB  - The environmental and/or life history factors affecting genetic exchange in
      marine species with potential for high dispersal are of great interest, not only
      from an evolutionary standpoint but also with regard to effective management.
      Previous genetic studies have demonstrated substantial differentiation among
      populations of the Patagonian toothfish around the Southern Ocean, indicating
      breakdown of gene flow across large distances between inhabited shelf areas. The
      present study examined genetic structuring through analysis of microsatellite
      loci and restriction fragment length polymorphism (RFLP) of the mitochondrial ND2
      gene and control region of the toothfish population in the SW Atlantic, allowing
      examination of the relative effects of the Antarctic Polar Front (APF), deep
      water troughs and distance between sites. Mitochondrial DNA (mtDNA) data
      indicated a sharp genetic division between the Patagonian Shelf/North Scotia
      Ridge and the Shag Rocks/South Georgia samples, whereas microsatellite data
      showed much less distinct structuring and an intermediate position of the North
      Scotia Ridge samples. We suggest these data indicate that the APF, as a barrier
      to larval dispersal, is the major inhibitor of genetic exchange between toothfish
      populations, with deep-water troughs and distance between sites contributing to
      genetic differentiation by inhibiting migration of relatively sedentary adults.
      We also suggest that differences between mtDNA and nuclear DNA population
      patterns may reflect either genome population size effects or (putative) male
      biased dispersal.

PMID- 15487991
TI  - Spatial and population genetic structure of microsatellites in white pine.
AB  - We evaluated the population genetic structure of seven microsatellite loci for
      old growth and second growth populations of eastern white pine (Pinus strobus).
      From each population, located within Hartwick Pines State Park, Grayling,
      Michigan, USA, 120-122 contiguous trees were sampled for genetic analysis. Within
      each population, genetic diversity was high and inbreeding low. When comparing
      these populations, there is a significant, but small (less than 1%), genetic
      divergence between populations. Spatial distance between populations or timber
      harvest at the second growth site were reasonable explanations for the observed
      minor differences in allele frequencies between populations. Spatial
      autocorrelation analysis suggested that, for the old growth population, weak
      positive structuring at 15 m fits the isolation by distance model for a
      neighbourhood size of about 100 individuals. In comparison, genotypes were
      randomly distributed in the second growth population. Thus, logging may have
      decreased spatial structuring at the second growth site, suggesting that
      management practices may be used to alter natural spatial patterns. In addition,
      the amount of autocorrelation in the old growth population appears to be lower
      for some of the microsatellites, suggesting higher numbers of rare alleles and
      that higher mutation rates may have directly affected spatial statistics by
      reducing structure.

PMID- 15487992
TI  - Genetic diversity and population structure of the commercially harvested sea
      urchin Paracentrotus lividus (Echinodermata, Echinoidea).
AB  - The population structure of the edible Atlanto-Mediterranean sea urchin
      Paracentrotus lividus is described by analysing sequence variation in a fragment
      of the mitochondrial gene cytochrome c oxidase subunit I in 127 individuals from
      12 localities across south-west Europe. The study revealed high levels of genetic
      diversity but low levels of genetic structure, suggesting a large degree of gene
      flow between populations and panmixis within each, the Mediterranean and Atlantic
      basins. However, we found significant genetic differentiation between the two
      basins probably due to restricted gene flow across the geographical boundary
      imposed by the area of the Strait of Gibraltar. Populations of P. lividus
      appeared to have experienced a recent demographic expansion in the late
      Pleistocene. We provide new evidence on the population structure of this
      commercial species, predicting a healthy stock of this sea urchin on the
      Mediterranean and Atlantic coasts.

PMID- 15487993
TI  - Phylogeography recapitulates topography: very fine-scale local endemism of a
      saproxylic 'giant' springtail at Tallaganda in the Great Dividing Range of south
      east Australia.
AB  - Comparative phylogeography can reveal processes and historical events that shape
      the biodiversity of species and communities. As part of a comparative research
      program, the phylogeography of a new, endemic Australian genus and species of log
      dependent (saproxylic) collembola was investigated using mitochondrial sequences,
      allozymes and anonymous single-copy nuclear markers. We found the genetic
      structure of the species corresponds with five a priori microbiogeographical
      regions, with population subdivision at various depths owing to palaeoclimatic
      influences. Closely related mtDNA haplotypes are codistributed within a single
      region or occur in adjacent regions, nuclear allele frequencies are more similar
      among more proximate populations, and interpopulation migration is rare. Based on
      mtDNA divergence, a late Miocene-late Pliocene coalescence is likely. The present
      day distribution of genetic diversity seems to have been impacted by three major
      climatic events: Pliocene cooling and drying (2.5-7 million years before present,
      Mybp), early Pleistocene wet-dry oscillations (c. 1.2 Mybp) and the more recent
      glacial-interglacial cycles that have characterized the latter part of the
      Quaternary (<0.4 Mybp).

PMID- 15487994
TI  - Microsatellite and mitochondrial DNA analyses of Atlantic bluefin tuna (Thunnus
      thynnus thynnus) population structure in the Mediterranean Sea.
AB  - Genetic variation was surveyed at nine microsatellite loci and the mitochondrial
      control region (868 bp) to test for the presence of genetic stock structure in
      young-of-the-year Atlantic bluefin tuna (Thunnus thynnus thynnus) from the
      Mediterranean Sea. Bluefin tuna were sampled over a period of 5 years from the
      Balearic and Tyrrhenian seas in the western basin of the Mediterranean Sea, and
      from the southern Ionian Sea in the eastern basin of the Mediterranean Sea.
      Analyses of multilocus microsatellite genotypes and mitochondrial control region
      sequences revealed no significant heterogeneity among collections taken from the
      same location in different years; however, significant spatial genetic
      heterogeneity was observed across all samples for both microsatellite markers and
      mitochondrial control region sequences (FST=0.0023, P=0.038 and PhiST=0.0233,
      P=0.000, respectively). Significant genetic differentiation between the
      Tyrrhenian and Ionian collections was found for both microsatellite and
      mitochondrial markers (FST=0.0087, P=0.015 and PhiST=0.0367, P=0.030,
      respectively). These results suggest the possibility of a genetically discrete
      population in the eastern basin of the Mediterranean Sea.

PMID- 15487995
TI  - Mitochondrial DNA variation and population structure of the island endemic
      Azorean bat (Nyctalus azoreum).
AB  - The Azorean bat Nyctalus azoreum is the only endemic mammal native to the remote
      archipelago of the Azores. It evolved from a continental ancestor related to the
      Leisler's bat Nyctalus leisleri and is considered threatened because of its
      restricted and highly fragmented distribution. We studied the genetic variability
      in 159 individuals from 14 colonies sampled throughout the archipelago. Sequences
      of the D-loop region revealed moderate but highly structured genetic variability.
      Half of the 15 distinct haplotypes were restricted to a single island, but the
      most common was found throughout the archipelago, suggesting a single
      colonization event followed by limited interisland female gene flow. All N.
      azoreum haplotypes were closely related and formed a star-like structure typical
      of expanded populations. The inferred age of demographic expansions was
      consistent with the arrival of founder animals during the Holocene, well before
      the first humans inhabited the Azores. Comparisons with a population of N.
      leisleri from continental Portugal confirmed not only that all N. azoreum
      lineages were unique to the archipelago, but also that the current levels of
      genetic diversity were surprisingly high for an insular species. Our data imply
      that the Azorean bat has a high conservation value. We argue that geographical
      patterns of genetic structuring indicate the existence of two management units.

PMID- 15487996
TI  - Strong fungal specificity and selectivity for algal symbionts in Florida scrub
      Cladonia lichens.
AB  - Symbiosis is a major theme in the history of life and can be an important force
      driving evolution. However, across symbioses, it is difficult to tease apart the
      mechanisms that structure the interactions among potential partners. We used
      genetic similarity and frequency-based methods to qualitatively and
      quantitatively examine the patterns of association among several co-occurring
      Cladonia lichen fungi and their algal photobionts in six disjunct Florida scrub
      sites. The patterns of association were described by the degree of specificity,
      i.e. the phylogenetic range of associated partners, and of selectivity, i.e. the
      frequency of association among partners. Six fungal species associated with only
      one algal internal transcribed spacer clade, with the remaining two fungi being
      associated with two algal clades. In all cases, the fungi associated in unequal
      frequencies with the observed algal photobiont genotypes within those clades-
      suggesting that both specificity and selectivity were higher than expected.
      Fungal species can be grouped into three significantly different specificity
      classes: photobiont specialists, intermediates and generalists. In contrast to
      the pronounced specificity for photobionts among fungal species, the different
      Florida scrub sites do not harbour distinct photobiont pools, and differential
      photobiont availability cannot explain the patterning of lichen associations at
      this spatial scale. Therefore, we conclude that fungal specificity and
      selectivity for algal photobionts are major factors in determining the local
      composition of symbiotic partnerships.

PMID- 15487997
TI  - Lower fitness of hatchery and hybrid rainbow trout compared to naturalized
      populations in Lake Superior tributaries.
AB  - We have documented an early life survival advantage by naturalized populations of
      anadromous rainbow trout Oncorhynchus mykiss over a more recently introduced
      hatchery population and outbreeding depression resulting from interbreeding
      between the two strains. We tested the hypothesis that offspring of naturalized
      and hatchery trout, and reciprocal hybrid crosses, survive equally from fry to
      age 1+ in isolated reaches of Lake Superior tributary streams in Minnesota. Over
      the first summer, offspring of naturalized females had significantly greater
      survival than offspring of hatchery females in three of four comparisons (two
      streams and 2 years of stocking). Having an entire naturalized genome, not just a
      naturalized mother, was important for survival over the first winter. Naturalized
      offspring outperformed all others in survival to age 1+ and hybrids had reduced,
      but intermediate, survival relative to the two pure crosses. Averaging over years
      and streams, survival relative to naturalized offspring was 0.59 for hybrids with
      naturalized females, 0.37 for the reciprocal hybrids, and 0.21 for hatchery
      offspring. Our results indicate that naturalized rainbow trout are better adapted
      to the conditions of Minnesota's tributaries to Lake Superior so that they
      outperform the hatchery-propagated strain in the same manner that many native
      populations of salmonids outperform hatchery or transplanted fish. Continued
      stocking of the hatchery fish may conflict with a management goal of sustaining
      the naturalized populations.

PMID- 15487998
TI  - Major histocompatibility complex and microsatellite variation in two populations
      of wild gorillas.
AB  - In comparison to their close relatives the chimpanzees and humans, very little is
      known concerning the amount and structure of genetic variation in gorillas. Two
      species of gorillas are recognized and while the western gorillas number in the
      tens of thousands, only several hundred representatives of the mountain gorilla
      subspecies of eastern gorillas survive. To analyse the possible effects of these
      different population sizes, this study compares the variation observed at
      microsatellite and major histocompatibility complex (MHC) loci in samples of wild
      western and mountain gorillas, collected using a sampling scheme that targeted
      multiple social groups within defined geographical areas. Noninvasive samples
      proved a viable source of DNA for sequence analysis of the second exon of the DRB
      loci of the MHC. Observed levels of variation at the MHC locus were similar
      between the two gorilla species and were comparable to those in other primates.
      Comparison of results from analysis of variation at multiple microsatellite loci
      found only a slight reduction in heterozygosity for the mountain gorillas despite
      the relatively smaller population size.

PMID- 15487999
TI  - Neutral genetic variation among wild North American populations of the weedy
      plant Arabidopsis thaliana is not geographically structured.
AB  - We investigated neutral genetic variation within and among 53 wild-collected
      populations of the weedy annual plant, Arabidopsis thaliana, in North America,
      using amplified fragment length polymorphism (AFLP) markers. A. thaliana is
      thought to have been introduced to North America from Eurasia by humans; such an
      introduction might be expected to leave a clear geographical signal in the
      genetic data. To detect such patterns, we sampled populations at several
      hierarchical geographical levels. We collected individuals from populations in
      two areas of the Southeast and one in the Midwest, as well as individuals from
      populations in the Pacific Northwest and Northeast. To estimate within-population
      variation, we sampled eight individuals from each of six populations in the
      Southeast and Midwest. Among all 95 individuals analysed, we detected 131
      polymorphic AFLP fragments. We found no evidence for continental or regional
      diversification. Individuals sampled from Midwestern and Southeastern populations
      intermingled in a neighbour-joining tree, and Mantel tests conducted within the
      Midwestern and Southeastern regions as well as the full data set failed to detect
      any significant relationship between geographical and genetic distance. These
      results mirror those found for most global surveys of neutral genetic variability
      in A. thaliana. Surprisingly, we detected substantial amounts of neutral genetic
      variability within populations. The levels of genetic variation within
      populations, coupled with the nongeographical nature of divergence among
      populations, are consistent with contemporary gene flow and point to a complex
      and dynamic population history of A. thaliana in North America.

PMID- 15488000
TI  - Nonallopatric and parallel origin of local reproductive barriers between two
      snail ecotypes.
AB  - Theory suggests that speciation is possible without physical isolation of
      populations (hereafter, nonallopatric speciation), but recent nonallopatric
      models need the support of irrefutable empirical examples. We collected snails
      (Littorina saxatilis) from three areas on the NW coast of Spain to investigate
      the population genetic structure of two ecotypes. Earlier studies suggest that
      these ecotypes may represent incipient species: a large, thick-shelled 'RB'
      ecotype living among the barnacles in the upper intertidal zone and a small, thin
      shelled 'SU' ecotype living among the mussels in the lower intertidal zone only
      10-30 m away. The two ecotypes overlap and hybridize in a midshore zone only 1-3
      m wide. Three different types of molecular markers [allozymes, mitochondrial DNA
      (mtDNA) and microsatellites] consistently indicated partial reproductive
      isolation between the RB and the SU ecotypes at a particular site. However, each
      ecotype was related more closely to the other ecotype from the same site than to
      the same ecotype from another site further along the Galician coast (25-77 km
      away). These findings supported earlier results based solely on allozyme
      variation and we could now reject the possibility that selection produced these
      patterns. The patterns of genetic variation supported a nonallopatric model in
      which the ecotypes are formed independently at each site by parallel evolution
      and where the reproductive barriers are a byproduct of divergent selection for
      body size. We argue that neither our laboratory hybridization experiments nor our
      molecular data are compatible with a model based on allopatric ecotype formation,
      secondary overlap and introgression.

PMID- 15488001
TI  - Rivers influence the population genetic structure of bonobos (Pan paniscus).
AB  - Bonobos are large, highly mobile primates living in the relatively undisturbed,
      contiguous forest south of the Congo River. Accordingly, gene flow among
      populations is assumed to be extensive, but may be impeded by large, impassable
      rivers. We examined mitochondrial DNA control region sequence variation in
      individuals from five distinct localities separated by rivers in order to
      estimate relative levels of genetic diversity and assess the extent and pattern
      of population genetic structure in the bonobo. Diversity estimates for the bonobo
      exceed those for humans, but are less than those found for the chimpanzee. All
      regions sampled are significantly differentiated from one another, according to
      genetic distances estimated as pairwise FSTs, with the greatest differentiation
      existing between region East and each of the two Northern populations (N and NE)
      and the least differentiation between regions Central and South. The distribution
      of nucleotide diversity shows a clear signal of population structure, with some
      30% of the variance occurring among geographical regions. However, a geographical
      patterning of the population structure is not obvious. Namely, mitochondrial
      haplotypes were shared among all regions excepting the most eastern locality and
      the phylogenetic analysis revealed a tree in which haplotypes were intermixed
      with little regard to geographical origin, with the notable exception of the
      close relationships among the haplotypes found in the east. Nonetheless, genetic
      distances correlated with geographical distances when the intervening distances
      were measured around rivers presenting effective current-day barriers, but not
      when straight-line distances were used, suggesting that rivers are indeed a
      hindrance to gene flow in this species.

PMID- 15488002
TI  - Chloroplast DNA variation and postglacial recolonization of common ash (Fraxinus
      excelsior L.) in Europe.
AB  - We used chloroplast polymerase chain reaction-restriction-fragment length
      polymorphism (PCR-RFLP) and chloroplast microsatellites to assess the structure
      of genetic variation and postglacial history across the entire natural range of
      the common ash (Fraxinus excelsior L.), a broad-leaved wind-pollinated and wind
      dispersed European forest tree. A low level of polymorphism was observed, with
      only 12 haplotypes at four polymorphic microsatellites in 201 populations, and
      two PCR-RFLP haplotypes in a subset of 62 populations. The clear geographical
      pattern displayed by the five most common haplotypes was in agreement with
      glacial refugia for ash being located in Iberia, Italy, the eastern Alps and the
      Balkan Peninsula, as had been suggested from fossil pollen data. A low
      chloroplast DNA mutation rate, a low effective population size in glacial refugia
      related to ash's life history traits, as well as features of postglacial
      expansion were put forward to explain the low level of polymorphism.
      Differentiation among populations was high (GST= 0.89), reflecting poor mixing
      among recolonizing lineages. Therefore, the responsible factor for the highly
      homogeneous genetic pattern previously identified at nuclear microsatellites
      throughout western and central Europe (Heuertz et al. 2004) must have been
      efficient postglacial pollen flow. Further comparison of variation patterns at
      both marker systems revealed that nuclear microsatellites identified complex
      differentiation patterns in south-eastern Europe which remained undetected with
      chloroplast microsatellites. The results suggest that data from different markers
      should be combined in order to capture the most important genetic patterns in a
      species.

PMID- 15488003
TI  - Molecular evidence for Pleistocene glacial cycles driving diversification of a
      North American desert spider, Agelenopsis aperta.
AB  - The influence of historical climatic vs. geological changes on species
      diversification patterns was investigated in a widely distributed North American
      desert spider, Agelenopsis aperta (Araneae: Agelenidae), with particular
      reference to Pleistocene glacial cycles and earlier patterns of mountain
      building. Levels of sequence divergence obtained from the mitochondrial gene,
      cytochrome oxidase I, dated to the Pleistocene, eliminating Rocky Mountain
      orogeny as a cause of diversification, as orogeny ended 4 million years ago. The
      results of phylogenetic and network analyses showed the presence of three
      geographically defined clades, which were consistent with the presence of at
      least three glacial refugia: (i) east of the Rocky Mountains; (ii) between the
      Rocky Mountains and Sierra Nevadas; and (iii) west of the Sierra Nevadas. In
      addition, populations within the Rocky Mountains exhibited significantly lower
      genetic diversity than populations east of the Rocky Mountains and the haplotypes
      found within the Rockies were a subset of eastern haplotypes. These patterns
      suggest that a post-Pleistocene range expansion occurred out of an eastern
      glacial refugium into the Rocky Mountains. Examination of phylogeographical
      studies of other North American desert taxa indicated that mountain building
      explained diversification patterns more effectively for some taxa but Pleistocene
      climate change was more important for others, including A. aperta.

PMID- 15488004
TI  - Chloroplast DNA variation in the Quercus affinis-Q. laurina complex in Mexico:
      geographical structure and associations with nuclear and morphological variation.
AB  - The geographical distribution of chloroplast DNA (cpDNA) variation in 39
      populations of two hybridizing Mexican red oaks, Quercus affinis and Q. laurina,
      was investigated using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). Six haplotypes were identified. Of these, two (H1 and
      H4), separated by four mutations, had high frequencies (58 and 23% of the
      individuals, respectively) and were present across the whole geographical range
      of both species, often co occurring in the same populations. The other four
      haplotypes were rare, geographically restricted, and are probably derived from
      the two frequent haplotypes. Latitudinal or other clinal patterns in diversity
      levels or haplotype composition of populations were not apparent. The pattern of
      haplotype distribution was characterized by some mosaicism, with contrasting
      populations often situated in proximity. Average within-population diversity
      (hS=0.299) and population differentiation (GST=0.499) were, respectively, higher
      and lower than values reported in previous studies of oak species. There was
      evidence for phylogeographical structure, as indicated by NST (0.566) being
      significantly higher than GST. Haplotypic variation was largely species
      independent, although some very weak associations were detected between
      haplotypes H1 and H4 and morphological and nuclear molecular variation
      correspondingly characterizing Q. affinis and Q. laurina. These oaks probably did
      not experience a marked restriction to one or a few particular subregions of
      their present range during the last glacial cycle. It is more likely that
      substantial populations persisted throughout several episodes of climatic change,
      but experienced recurrent latitudinal and altitudinal migrations which may have
      caused the widespread distribution of haplotypes H1 and H4 and frequent
      intermixing of populations.

PMID- 15488005
TI  - Admixture and diversity in West African cattle populations.
AB  - We present a population genetic analysis of microsatellite variation in 16 West
      African cattle populations. West Africa represents a unique juxtaposition of
      different climatic and ecological zones in a relatively small geographical area.
      While more humid coastal regions are inhabited by the tsetse fly, a vector which
      spreads trypanosomiasis among cattle, the disease is not transmitted in the drier
      areas outside this zone. This is the most thorough study of genetic diversity in
      cattle within this area, which contains genetically important trypanotolerant Bos
      taurus breeds. Genetic relationships among the many breeds are examined and
      levels of diversity are assessed. Admixture levels were determined using a
      variety of methods. Ancestry informative or population-associated alleles (PAAs)
      were selected using populations from India, the Near East and Europe.
      Multivariate analysis, the admix program and model-based Bayesian admixture
      analysis approaches were also employed. These analyses reveal the direct impact
      of ecological factors and the profound effect of admixture on the cattle of this
      region. They also highlight the importance of efforts to prevent further dilution
      of African taurine breeds by B. indicus cattle.

PMID- 15488006
TI  - Geological barriers and restricted gene flow in the holarctic skipper Hesperia
      comma (Hesperiidae).
AB  - Patterns of genetic variation within a species may be a consequence of historical
      factors, such as past fragmentation, as well as current barriers to gene flow.
      Using sequence data from the mitochondrial cytochrome oxidase subunit II region
      (COII) and the nuclear gene wingless, we conducted a phylogeographical study of
      the holarctic skipper Hesperia comma to elucidate patterns of genetic diversity
      and to infer historical and contemporary processes maintaining genetic variation.
      One hundred and fifty-one individuals were sampled from throughout North America
      and Eurasia, focusing on California and adjacent regions in the western United
      States where morphological diversity is highest compared to the rest of the
      range. Analyses of sequence data obtained from both genes revealed a well
      supported division between the Old and New World. Within western North America,
      wingless shows little geographical structure, while a hierarchical analysis of
      genetic diversity of COII sequences indicates three major clades: a western clade
      in Oregon and Northern California, an eastern clade including the Great Basin,
      Rocky Mountains and British Columbia, and a third clade in southern California.
      The Sierra Nevada and the Transverse Ranges appear to be the major barriers to
      gene flow for H. comma in the western United States. Relatively reduced haplotype
      diversity in Eurasia compared to North America suggests that populations on the
      two continents have been affected by different historical processes.

PMID- 15488007
TI  - Mitochondrial gene diversity in the common vole Microtus arvalis shaped by
      historical divergence and local adaptations.
AB  - The phylogeography of the common vole (Microtus arvalis) was examined by
      analysing mitochondrial DNA (mtDNA) sequence variation in 1044 base pairs (bp) of
      the cytochrome b (cytb) gene and in 322 bp of the control region (ctr) among 106
      individuals from 58 locations. The geographical distribution of four previously
      recognized cytb evolutionary lineages in Europe was refined and a new lineage was
      found in southern Germany. All lineages were distributed allopatrically, except
      in one sample that was probably located in a contact zone. The occurrence of
      several lineages in the Alps is in keeping with their recent recolonization from
      distinct sources. The translation of 84 cytb DNA sequences produced 33 distinct
      proteins with relationships that differed from those of the DNA haplotypes,
      suggesting that the mtDNA lineages did not diverge in response to selection. In
      comparison with M. agrestis, a neutrality test detected no overall evidence for
      selection in the cytb gene, but a closer examination of a structural model showed
      that evolutionarily conserved and functionally important positions were often
      affected. A new phylogeographical test of random accumulation of nonsynonymous
      mutations generated significant results in three lineages. We therefore conclude
      that the molecular diversity of cytb in M. arvalis is overall the result of the
      demographic history of the populations, but that there have been several episodes
      of local adaptation to peculiar environments.

PMID- 15488008
TI  - Reconciling geography and genealogy: phylogeography of giant freshwater prawns
      from the Lake Carpentaria region.
AB  - There is convincing geological evidence for the historical existence of an
      ancient lake on the Australian-New Guinea continental shelf during the late
      Pleistocene. Lake Carpentaria was a vast fresh- to brackishwater lake that would
      presumably have provided habitat for, and facilitated gene flow among, aquatic
      taxa that tolerate low to moderate salinities in this region. Moreover, it has
      been argued that the outflow of Papua New Guinea's Fly River was diverted
      westward into Lake Carpentaria during this period, although this hypothesis is
      controversial. We predicted that these events, if a true history, would have
      promoted gene flow and population growth via range-expansion events in the giant
      freshwater prawn (Macrobrachium rosenbergii) and restricted gene flow
      subsequently by way of a vicariant event as sea levels rose during the late
      Pleistocene, and a marine environment replaced Lake Carpentaria. We tested these
      hypotheses using phylogeographical and phylogenetic analyses of mitochondrial DNA
      variation in M. rosenbergii populations sampled from the Lake Carpentaria region.
      Our results support the hypothesis that Lake Carpentaria facilitated gene flow
      among populations of M. rosenbergii that are today isolated, but contest claims
      of a westward diversion of the Fly River. We inferred the timing of initial
      expansion in the 'Lake Carpentaria lineage' and found the timing of this event to
      be broadly concordant with geological dating of the formation of Lake
      Carpentaria. Reconciling geological and molecular data, as presented here,
      provides a powerful framework for investigating the influence of historical earth
      history events on the distribution of biological (i.e. molecular) diversity.

PMID- 15488009
TI  - Hidden Floridian biodiversity: mitochondrial and nuclear gene trees reveal four
      cryptic species within the scorched mussel, Brachidontes exustus, species
      complex.
AB  - The well-documented Floridian 'Gulf/Atlantic' marine genetic disjunction provides
      an influential example of vicariant cladogenesis along a continental coastline
      for major elements of a diverse nearshore fauna. We are engaged in a two-part
      study that aims to place this disjunction into a regional Caribbean Basin
      phylogenetic perspective using the scorched mussel Brachidontes exustus as an
      exemplar. Our first step, documented here, is to thoroughly characterize the
      genetic structure of Floridian scorched mussel populations using mitochondrial
      (mt) and nuclear markers. Both sets of markers recovered the expected disjunction
      involving sister clades distributed on alternate flanks of peninsular Florida and
      lineage-specific mt molecular clocks placed its origin in the Pliocene. The two
      sister clades had distinct population genetic profiles and the Atlantic clade
      appears to have experienced an evolutionarily recent bottleneck, although plots
      of the relative estimates of N through time are consistent with its local
      persistence through the last Ice Age Maximum. Our primary novel result, however,
      was the discovery that the Gulf/Atlantic disjunction represents but one of three
      cryptic, nested genetic discontinuities represented in Floridian scorched mussel
      populations. The most pronounced phylogenetic split distinguished the Gulf and
      Atlantic sister clades from two additional nested cryptic sister clades present
      in samples taken from the southern Florida tropical marine zone. Floridian
      populations of B. exustus are composed of four cryptic taxa, a result consistent
      with the hypothesis that the Gulf/Atlantic disjunction in this morphospecies is
      but one of multiple latent regional genetic breakpoints.

PMID- 15488010
TI  - The rate of fertilization in male mating tactics of the polygynous grey seal.
AB  - Studies using molecular markers have shown that some grey seal males may be
      gaining success through exhibiting alternative mating tactics. We estimated the
      probability of fertilization success of grey seal males exhibiting the primary
      tactic of female defence and one alternative tactic of mating with departing
      females on Sable Island, Nova Scotia, Canada, during the breeding seasons of 1997
      2002. Although the fertilization rate of the primary tactic (27-43%) was greater
      than that of the alternative tactic (10-12%), these low rates indicate the
      potential fitness value of alternative mating tactics in this size-dimorphic
      pinniped species.

PMID- 15488011
TI  - Prey selection by linyphiid spiders: molecular tracking of the effects of
      alternative prey on rates of aphid consumption in the field.
AB  - A molecular approach, using aphid-specific monoclonal antibodies, was used to
      test the hypothesis that alternative prey can affect predation on aphids by
      linyphiid spiders. These spiders locate their webs in cereal crops within
      microsites where prey density is high. Previous work demonstrated that of two
      subfamilies of Linyphiidae, one, the Linyphiinae, is web-dependent and makes its
      webs at sites where they were more likely to intercept flying insects plus those
      (principally aphids) falling from the crop above. The other, the Erigoninae, is
      less web-dependent, making its webs at ground level at sites with higher
      densities of ground-living detritivores, especially Collembola. The guts of the
      spiders were analysed to detect aphid proteins using enzyme-linked immunosorbent
      assay (ELISA). Female spiders were consuming more aphid than males of both
      subfamilies and female Linyphiinae were, as predicted, eating more aphid than
      female Erigoninae. Rates of predation on aphids by Linyphiinae were related to
      aphid density and were not affected by the availability of alternative prey.
      However, predation by the Erigoninae on aphids was significantly affected by
      Collembola density. Itinerant Linyphiinae, caught away from their webs, contained
      the same concentration of aphid in their guts as web-owners. However, nonweb
      owning Erigoninae, living away from Collembola aggregations at web-sites,
      contained significantly higher concentrations of aphid. For both subfamilies
      there was evidence of a disproportionate increase in predation on aphids once
      Collembola populations had declined. It was concluded that nonaphid prey, by
      helping to maintain spiders in the field, can significantly affect predation on
      aphids.

PMID- 15488012
TI  - Breeding system and demography shape population genetic structure across
      ecological and climatic zones in the African freshwater snail, Bulinus forskalii
      (Gastropoda, Pulmonata), intermediate host for schistosomes.
AB  - The role of breeding system and population bottlenecks in shaping the
      distribution of neutral genetic variation among populations inhabiting patchily
      distributed, ephemeral water bodies was examined for the hermaphroditic
      freshwater snail Bulinus forskalii, intermediate host for the medically important
      trematode Schistosoma guineensis. Levels of genetic variation at 11
      microsatellite loci were assessed for 600 individuals sampled from 19 populations
      that span three ecological and climatic zones (ecozones) in Cameroon, West
      Africa. Significant heterozygote deficiencies and linkage disequilibria indicated
      very high selfing rates in these populations. Despite this and the large genetic
      differentiation detected between populations, high levels of genetic variation
      were harboured within these populations. The high level of gene flow inferred
      from assignment tests may be responsible for this pattern. Indeed, metapopulation
      dynamics, including high levels of gene flow as well as extinction/contraction
      and recolonization events, are invoked to account for the observed population
      structuring, which was not a consequence of isolation-by-distance. Because B.
      forskalii populations inhabiting the northern, Sahelian area are subject to more
      pronounced annual cycles of drought and flood than the southern equatorial ones,
      they were expected to be subject to population bottlenecks of increased frequency
      and severity and, therefore, show reduced genetic variability and elevated
      population differentiation. Contrary to predictions, the populations inhabiting
      the most northerly ecozone exhibited higher genetic diversity and lower genetic
      differentiation than those in the most southerly one, suggesting that elevated
      gene flow in this region is counteracting genetic drift.

PMID- 15488013
TI  - Variation in pollen dispersal between years with different pollination conditions
      in a tropical emergent tree.
AB  - We examined differences in pollen dispersal efficiency between 2 years in terms
      of both spatial dispersal range and genetic relatedness of pollen in a tropical
      emergent tree, Dipterocarpus tempehes. The species was pollinated by the giant
      honeybee (Apis dorsata) in a year of intensive community-level mass-flowering or
      general flowering (1996), but by several species of moths in a year of less
      intensive general flowering (1998). We carried out paternity analysis based on
      six DNA microsatellite markers on a total of 277 mature trees forming four
      spatially distinct subpopulations in a 70 ha area, and 147 and 188 2-year-old
      seedlings originating from seeds produced in 1996 and 1998 (cohorts 96 and 98,
      respectively). Outcrossing rates (0.93 and 0.96 for cohorts 96 and 98,
      respectively) did not differ between years. Mean dispersal distances (222 and 192
      m) were not significantly different between the 2 years but marginally more
      biased to long distance in 1996. The mean relatedness among cross-pollinated
      seedlings sharing the same mothers in cohort 96 was lower than that in cohort 98.
      This can be attributed to the two facts that the proportion of
      intersubpopulations pollen flow among cross-pollination events was marginally
      higher in cohort 96 (44%) than in cohort 98 (33%), and that mature trees within
      the same subpopulations are genetically more related to each other than those
      between different subpopulations. We conclude that D. tempehes maintained
      effective pollen dispersal in terms of outcrossing rate and pollen dispersal
      distance in spite of the large difference in foraging characteristics between two
      types of pollinators. In terms of pollen relatedness, however, a slight
      difference was suggested between years in the level of biparental inbreeding.

PMID- 15488014
TI  - Quantitative trait loci affecting knockdown resistance to high temperature in
      Drosophila melanogaster.
AB  - Knockdown resistance to high temperature is an ecologically important trait in
      small insects. A composite interval mapping was performed on the two major
      autosomes of Drosophila melanogaster to search for quantitative trait loci (QTL)
      affecting knockdown resistance to high temperature (KRHT). Two dramatically
      divergent lines from geographically different thermal environments were
      artificially selected on KRHT. These lines were crossed to produce two backcross
      (BC) populations. Each BC was analysed for 200 males with 18 marker loci on
      chromosomes 2 and 3. Three X-linked markers were used to test for X-linked QTL in
      an exploratory way. The largest estimate of autosome additive effects was found
      in the pericentromeric region of chromosome 2, accounting for 19.26% (BC to the
      low line) and 29.15% (BC to the high line) of the phenotypic variance in BC
      populations, but it could represent multiple closely linked QTL. Complete
      dominance was apparent for three QTL on chromosome 3, where heat-shock genes are
      concentrated. Exploratory analysis of chromosome X indicated a substantial
      contribution of this chromosome to KRHT. The results show that a large-effect QTL
      with dominant gene action maps on the right arm of chromosome 3. Further, the
      results confirm that QTL for heat resistance are not limited to chromosome 3.

PMID- 15488015
TI  - Molecular markers reveal extensive intraspecific below-ground overlap of silver
      fir fine roots.
AB  - Fine roots are expected to be important determinants of plant competition, but
      very little is known about the extent of root system overlap. Here, we describe
      the application of two highly variable plastide microsatellites to study the fine
      root distribution of tree individuals in a silver fir forest. We demonstrate that
      the spread of fine roots exceeds the width of above-ground parts, and that fine
      root overlaps among neighbouring trees are extensive both laterally and in depth.
      This approach will help to improve models of below-ground competition and will
      facilitate estimations of fine root biomass and thus of below-ground C pools.

PMID- 15488016
TI  - Quantifying genotyping errors in noninvasive population genetics.
AB  - The use of noninvasively collected samples greatly expands the range of
      ecological issues that may be investigated through population genetics.
      Furthermore, the difficulty of obtaining reliable genotypes with samples
      containing low quantities of amplifiable DNA may be overcome by designing optimal
      genotyping schemes. Such protocols are mainly determined by the rates of
      genotyping errors caused by false alleles and allelic dropouts. These errors may
      not be avoided through laboratory procedure and hence must be quantified.
      However, the definition of genotyping error rates remains elusive and various
      estimation methods have been reported in the literature. In this paper we
      proposed accurate codification for the frequencies of false alleles and allelic
      dropouts. We then reviewed other estimation methods employed in hair- or faeces
      based population genetics studies and modelled the bias associated with erroneous
      methods. It is emphasized that error rates may be substantially underestimated
      when using an erroneous approach. Genotyping error rates may be important
      determinants of the outcome of noninvasive studies and hence should be carefully
      computed and reported.

PMID- 15488017
TI  - Costs and benefits of cold tolerance in transgenic Arabidopsis thaliana.
AB  - Cold tolerance in plants is an ecologically important trait that has been under
      intensive study for basic and applied reasons. Determining the fitness benefits
      and costs of cold tolerance has previously been difficult because cold tolerance
      is normally an induced trait that is not expressed in warm environments. The
      recent creation of transgenic plants constitutively expressing cold tolerance
      genes enables the investigation of the fitness consequences of cold tolerance in
      multiple temperature environments. We studied three genes from the CBF (C
      repeat/dehydration responsive element binding factor) cold tolerance pathway,
      CBF1, 2 and 3, in Arabidopsis thaliana to test for benefits and costs of
      constitutive cold tolerance. We used multiple insertion lines for each transgene
      and grew the lines in cold and control conditions. Costs of cold tolerance, as
      determined by fruit number, varied by individual transgene. CBF2 and 3
      overexpressers showed costs of cold tolerance, and no fitness benefits, in both
      environments. CBF1 overexpressing plants showed no fitness cost of cold tolerance
      in the control environment and showed a marginal fitness benefit in the cold
      environment. These results suggest that constitutive expression of traits that
      are normally induced in response to environmental stress will not always lead to
      costs in the absence of that stress, and that the ecological risks of CBF
      transgene escape should be assessed prior to their use in commercial agriculture.

PMID- 15488020
TI  - Vascular endothelial growth factor and the nervous system.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic factor essential for
      the formation of new blood vessels during embryogenesis and in many pathological
      conditions. A new role for VEGF as a neurotrophic factor has recently emerged. In
      the developing nervous system, VEGF plays a pivotal role not only in
      vascularization, but also in neuronal proliferation, and the growth of
      coordinated vascular and neuronal networks. After injury to the nervous system,
      activation of VEGF and its receptors may restore blood supply and promote
      neuronal survival and repair. There is a growing body of evidence that VEGF is
      essential for motor neurone survival, and that aberrant regulation of VEGF may
      play a role in the degeneration of neurones in diseases such as amyotrophic
      lateral sclerosis.

PMID- 15488021
TI  - Expression of glucose transporter 5 by microglia in human gliomas.
AB  - Our previous studies indicate that glucose transporter 5 (GLUT5) is a microglial
      marker in routine paraffin sections, and is rarely present in
      monocytes/macrophages of the peripheral organs. We examined the expression of
      GLUT5 in 91 cases of human gliomas to characterize the microglial phenotype in
      glioma tissues. Immunohistochemistry was performed on formalin-fixed, paraffin
      embedded sections using such antibodies as a GLUT5 antibody, two markers for
      activated microglia: major histocompatibility complex (MHC) class II Ag and
      macrophage scavenger receptor class A (MSR-A), and MIB-1 antibody. The
      immunoreactivity of GLUT5 was present in three microglial phenotypes: ramified
      (resting), activated, and ameboid (macrophagic) microglia in most of the cases. A
      double-labelling study of astrocytic tumours using GLUT5 and MIB-1 antibodies
      demonstrated a proportion of proliferating microglia. However, no morphological
      difference between MIB-1-positive, microglial cells and MIB-1-negative,
      microglial cells was found. The number of GLUT5-positive microglia was
      significantly (P < 0.001) higher in astrocytic tumours than in oligodendroglial
      tumours. Many GLUT5-positive microglia (up to 52% in total cells) were often
      observed in pilocytic astrocytomas, where microglial cells were predominantly
      ramified, and the number of MHC class II- or MSR-A-positive microglia was less
      than GLUT5-positive microglia. Thus, the present study indicated that intrinsic
      microglia can be a source of microglia/macrophages cell populations in astrocytic
      tumours, and that pilocytic astrocytomas often have a high proportion of
      microglial cells with mild activation.

PMID- 15488022
TI  - Imaging of iron oxide nanoparticles by MR and light microscopy in patients with
      malignant brain tumours.
AB  - OBJECTIVE: Ferumoxtran-10 (Combidex), a dextran-coated iron oxide nanoparticle,
      provides enhancement of intracranial tumours by magnetic resonance (MR) for more
      than 24 h and can be imaged histologically by iron staining. Our goal was to
      compare ferumoxtran imaging and histochemistry vs. gadolinium enhancement in
      malignant brain tumours on preoperative and postoperative MR. METHODS: Seven
      patients with primary and metastatic malignant tumours underwent MR imaging with
      gadolinium and ferumoxtran both pre- and postoperatively. Normalized signal
      intensities on the ferumoxtran-enhanced scans were determined in representative
      regions of interest. Resected tissue from six ferumoxtran patients and from three
      patients who did not receive ferumoxtran was assessed for localization of iron in
      tumour and reactive brain. RESULTS: All malignant tumours (all of which enhanced
      by gadolinium MR) showed ferumoxtran accumulation with T1 and T2 signal changes,
      even using a 0.15 T intraoperative MR unit in one patient. Iron staining was
      predominantly in reactive cells (reactive astrocytes and macrophages) and not
      tumour cells. In five of the seven patients, including two patients who showed
      additional lesions, areas enhancing with ferumoxtran but not with gadolinium were
      observed. Comparison of the pre- and postoperative MR revealed residual
      ferumoxtran-enhancing areas in four of seven cases. CONCLUSION: In malignant
      tumours, ferumoxtran may show areas of enhancement, even with a 0.15 T
      intraoperative MR, that do not enhance with gadolinium. Ferumoxtran-enhancing
      lesions have persistent increased T1 signal intensity for 2-5 days, which may
      provide advantages over gadolinium for postoperative imaging. Histochemistry for
      iron shows uptake of ferumoxtran in reactive cells (astrocytes and macrophages)
      rather than tumour cells.

PMID- 15488023
TI  - Ezrin expression in tissue microarray of primary and recurrent gliomas.
AB  - Malignant progression, infiltrative growth pattern and recurrencies after surgery
      are characteristic features of diffuse gliomas. Ezrin is a membrane-cytoskeleton
      linker protein expressed in several types of neoplasms. In experimental models,
      increased ezrin expression correlates with invasion of malignant glioma cells. We
      studied ezrin expression and its correlation with patient survival in 229 primary
      and recurrent astrocytomas (WHO grades II-IV), oligodendrogliomas (II-III) and
      oligoastrocytomas (II-III) of 113 patients. Ezrin expression as evaluated by
      immunohistochemistry and immunoblotting was detected in all studied glioma types.
      Staining intensity and number of immunoreactive cells correlated with increasing
      malignancy of astrocytomas and oligoastrocytomas (P = 0.001). Ezrin expression
      was strongest in astrocytomas (P = 0.006). Also oligodendrogliomas were positive
      for ezrin. High ezrin expression in primary gliomas correlated with shorter time
      to recurrence (P < 0.05) and poor overall survival (P < 0.05) of the patients.
      Ezrin expression increased during progression of the tumours (P < 0.05). However,
      ezrin was not an independent prognostic factor. The results of this study show
      that ezrin expression is associated with progression of gliomas and correlates
      with histological cell type and WHO tumour grade.

PMID- 15488024
TI  - HIV-1 expression protects macrophages and microglia from apoptotic death.
AB  - Macrophages and microglia are the predominant cells infected with HIV-1 in the
      brain, yet the effects of productive HIV infection on the fate of these cells are
      poorly understood. In this study, we tested the hypothesis that HIV-1 expression
      influences cell death in infected macrophages and microglial cells. We detected
      apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labelling (TUNEL) in the cerebral white matter of control and HIV encephalitis
      (HIVE) brains, and quantitatively analysed apoptotic cells with respect to their
      location (vessel-associated vs. parenchymal), CD68 expression, and HIV-1 p24
      expression. There were more vessel-associated, but not more parenchymal, TUNEL+
      cells in HIVE cases as compared to controls. Vessel-associated TUNEL+ cells were
      primarily endothelial cells (von Willebrand factor+) or macrophages (CD68+).
      TUNEL+/CD68+ cells were present in both control and HIVE cases in similar
      frequencies (2.1 +/- 0.7% vs. 1.9 +/- 0.7% of total CD68+ populations,
      respectively). In HIVE, TUNEL+/p24+ cells were 0.4 +/- 0.2% of the total p24+
      cell population, which was lower than the frequency of TUNEL+/CD68+ cells (1.9 +/
      0.7%) in the total CD68+ macrophage population. These results suggest that HIV-1
      infected macrophages and microglia are resistant to apoptosis, and may contribute
      to the formation of a central nervous system viral reservoir.

PMID- 15488025
TI  - Expression of stress-activated kinases c-Jun N-terminal kinase (SAPK/JNK-P) and
      p38 kinase (p38-P), and tau hyperphosphorylation in neurites surrounding betaA
      plaques in APP Tg2576 mice.
AB  - Hyperphosphorylated tau in neurites surrounding beta-amyloid (betaA) deposits, as
      revealed with phospho-specific anti-tau antibodies, are found in amyloid
      precursor protein (APP) Tg2576 mice. Because betaA is a source of oxidative
      stress and may be toxic for cultured cells, the present study examines the
      expression of phosphorylated (active) stress-activated kinase c-Jun N-terminal
      kinase (SAPK/JNK-P) and p38 kinase (p38-P), which have the capacity to
      phosphorylate tau at specific sites, and their specific substrates c-Jun and ATF
      2, which are involved in cell death and survival in several paradigms, in Tg2576
      mice. The study was planned to shed light about the involvement of these kinases
      in tau phosphorylation in cell processes surrounding amyloid plaques, as well as
      in the possible phosphorylation (activation) of c-Jun and activating
      transcription factor-2 (ATF-2) in relation to betaA deposition. Moderate increase
      in the expression of phosphorylated mitogen-activated protein kinase and
      extracelullar signal-regulated kinase (MAPK/ERK-P) occurs in a few amyloid
      plaques. However, strong expression of SAPK/JNK-P and p38-P is found in the
      majority of, if not all, amyloid plaques, as seen in serial consecutive sections
      stained for betaA and stress kinases. Moreover, confocal microscopy reveals
      colocalization of phospho-tau and SAPK/JNK-P, and phospho-tau and p38-P in many
      dystrophic neurites surrounding amyloid plaques. Increased expression levels of
      nonbound tau, SAPK/JNK-P and p38-P are corroborated by Western blots of total
      cortical homogenate supernatants in Tg2576 mice when compared with age-matched
      controls. No increase in phosphorylated c-JunSer63 (c-Jun-P) and ATF-2Thr71 (ATF
      2-P) is found in association with betaA deposits. In addition, no expression of
      active (cleaved) caspase-3 (17 kDa) has been found in transgenic mice. Taken
      together, these observations provide a link between betaA-induced oxidative
      stress, activation of stress kinases SAPK/JNK and p38, and tau
      hyperphosphorylation in neurites surrounding amyloid plaques, but activation of
      these kinases is not associated with accumulation of c-Jun-P and ATF-2-P, nor
      with activation of active caspase-3 in the vicinity of betaA deposits.

PMID- 15488026
TI  - Differential patterns of insulin-like growth factor-I and -II mRNA expression in
      medulloblastoma.
AB  - Insulin-like growth factors (IGFs) play an important role in tumour growth and
      development. We hypothesized that this is also the case for medulloblastomas,
      which are highly malignant cerebellar brain tumours usually occurring in
      children. In these tumours the expression patterns of IGF-I and -II mRNA were
      studied. Tumour specimens obtained from 12 children and two adults at diagnosis
      were hybridized in situ with digoxigenin-labelled cRNA probes for hIGF-I and hIGF
      II mRNAs. In all cases, tumour cells showed abundant expression of IGF-I mRNA.
      Nine of the 14 tumours showed variable but significant IGF-II expression. In
      these tumours, the hybridization signal almost exclusively colocalized with a
      subpopulation of Ki-M1P positive cells that were identified as ramified microglia
      (RM) cells. In the five tumours without IGF-II expression, microglia/brain
      macrophages with a more rounded amoeboid-like morphology predominated. RM cells
      in normal cerebellar tissues, residing abundantly in areas of the white and, to a
      less extent, in the grey matter, were IGF-II mRNA-negative. These RM cells showed
      a thinner and more extensively branched appearance and were more evenly
      distributed than those encountered in medulloblastoma. Probably, during the
      transformation from the resting ramified towards the amoeboid morphology (or vice
      versa) IGF-II mRNA expression is only temporarily induced. The physiological
      meaning of the induction of IGF-II mRNA expression by these cells in
      medulloblastoma remains unclear but any IGF-II peptide synthesized could exert
      unfavourable mitogenic and antiapoptotic effects on adjacent tumour cells.
      However, in this relatively small number of cases we could not find any
      indications for a relationship between clinical characteristics of the various
      cases and the extent of IGF-II mRNA expression.

PMID- 15488027
TI  - Bcl-2 expression inversely correlates with tumour cell differentiation in
      medulloblastoma.
AB  - Medulloblastoma (MB) is a cerebellar primitive neuroectodermal tumour that occurs
      predominantly in childhood. It can be mainly divided into classical and
      desmoplastic tumours, but differential diagnosis is often difficult. Patients'
      prognosis is poor and neuropathological markers that reliably predict outcome are
      still missing. In a series of 104 MBs including 80 tumours of the classical and
      24 tumours of the desmoplastic variant we studied the number of apoptotic figures
      and the expression of the proto-oncogene bcl-2, an anti-apoptotic protein known
      to affect tumour cell proliferation. We observed a strong correlation between the
      expression of bcl-2 with patients' age (P < 0.001) as well as with the
      desmoplastic subtype (P < 0.001). Here, protein expression was found to be
      restricted to internodular, less differentiated, highly proliferative areas. In
      classical MB, bcl-2 was detected only in 23% of cases and was highly inversely
      correlated with the expression of synaptophysin (P < 0.001) indicating that bcl-2
      is predominantly expressed by undifferentiated classical MB. With regard to
      prognosis the expression of bcl-2 tended to correlate with poor outcome in
      classical MB but not in desmoplastic MB, although not to a statistically
      significant extension (P = 0.06). On the other hand, a high number of apoptotic
      figures in the tumour tissue was found to indicate poor prognosis independent of
      the histological subtype (P < 0.05).

PMID- 15488028
TI  - Spinal motoneurone distress during experimental allergic encephalomyelitis.
AB  - The main pathophysiological feature characterizing multiple sclerosis (MS) is
      demyelination. However, the possibility of neural damage has recently been
      proposed as a mechanism in chronic disease. Experimental allergic
      encephalomyelitis (EAE) is the most widely used experimental model for MS. We
      investigated occurrences of microglial activation and astrocytosis in the spinal
      cord, choline acetyl-transferase (ChAT) and calcitonin gene-related peptide
      (CGRP) mRNA regulation in spinal motoneurones during EAE. EAE was induced in
      female Lewis rats by injecting guinea pig spinal cord tissue in complete Freund's
      adjuvant (CFA) to which heat-inactivated Mycobacterium had been added. Rats
      injected with CFA and uninjected rats were used as controls. ChAT and CGRP mRNAs
      were studied by in situ hybridization in the lumbar spinal cord and a
      computerized grain counting procedure was used for quantification. No differences
      in ChAT mRNA level were found between control and CFA-injected rats. ChAT mRNA
      level was strongly reduced in EAE 14 days after immunization and then recovered
      (29 days after immunization). CGRP mRNA increased 14 days after immunization, and
      then recovered to control level. Extensive long-lasting gliosis developed in the
      spinal cord and around motoneurones and a transient expression of p75LNGFR in
      motoneurones was also found. These data suggest that during EAE, gliosis induces
      distress in spinal cord neurones involving the synthesis enzyme for the main
      transmitter.

PMID- 15488029
TI  - No evidence for mutations or altered expression of the Suppressor of Fused gene
      (SUFU) in primitive neuroectodermal tumours.
AB  - The sonic hedgehog (Shh) and the Wnt signalling pathways are involved in the
      development of medulloblastomas (MBs), the most frequent malignant brain tumours
      in children. Components of these two developmental and cancer-associated
      pathways, including (Patched) PTCH, SMOH, adenomatous polyposis coli (APC), beta
      catenin and AXIN1 show somatic mutations in sporadic MBs. In this study we
      analysed SUFU (human Suppressor of Fused), which acts as a negative regulator of
      both the Shh and Wnt signalling pathways and therefore represents a putative
      tumour suppressor gene, to find out if it is also involved in the pathogenesis of
      sporadic MBs. We screened 145 primitive neuroectodermal tumours (PNETs) including
      90 classic MBs, 42 of the desmoplastic variant and two medullomyoblastomas as
      well as 11 MB cell lines for mutations using single-strand conformational
      polymorphism (SSCP) and sequencing analysis. 18% of the MBs exhibited allelic
      losses on chromosome 10q. In contrast to a previous report, in which truncating
      mutations of SUFU have been identified in 9% of MBs, we were not able to identify
      somatic mutations of SUFU in our large tumour panel. We uncovered single
      nucleotide polymorphisms (SNPs) in exon 4, 8, 11 and in intron 2 in the SUFU
      gene. Expression analysis by competitive reverse transcription-polymerase chain
      reaction (RT-PCR) revealed no difference in SUFU mRNA levels of both MB subtypes
      and normal foetal or adult cerebellar tissues. Our results indicate that genetic
      alterations of the SUFU gene, do not contribute significantly to the molecular
      pathogenesis of MBs.

PMID- 15488030
TI  - Absence of neuronal nitric oxide synthase (nNOS) as a pathological marker for the
      diagnosis of Becker muscular dystrophy with rod domain deletions.
AB  - Immunohistochemistry using antibodies to dystrophin is the pathological basis for
      the diagnosis of Duchenne and Becker muscular dystrophy (DMD and BMD). While the
      sarcolemma of DMD muscle is negative, BMD muscle generally shows variable
      labelling because of the translation of a partially functional dystrophin that is
      localized to the sarcolemma. In rare cases, however, this labelling is equivocal
      and similar to that observed in controls making diagnosis difficult. We report
      here that in such instances immunolabelling with antibodies to the neuronal form
      of nitric oxide synthase (nNOS) can be useful in suspecting a dystrophinopathy
      with a mutation in the 'hot-spot' rod domain and help to direct molecular
      analysis. nNOS localizes to the sarcolemma of mature muscle fibres via several
      components of the dystrophin-associated protein complex (DAPC) including
      dystrophin but sarcolemmal nNOS is lost when dystrophin levels are very low or
      absent because of deletions in critical regions of the rod domain. We report
      three cases who presented with only mild or no muscle weakness but had elevated
      serum creatine kinase activity and dystrophin immunolabelling indistinguishable
      from normal, making a pathological diagnosis difficult. All three cases had a
      complete absence of sarcolemmal nNOS and were subsequently found to have an in
      frame deletion in the common rod domain exons (in these cases 48, 45-51, 47-53)
      compatible with a BMD. In addition, we observed that nNOS appears to be
      developmentally regulated with the antibody used and was often absent from the
      sarcolemma of immature fibres. These findings demonstrate the value of including
      antibodies to nNOS in routine immunohistochemical studies and that absence of
      nNOS can be a more sensitive marker than up-regulation of utrophin for diagnosis
      of BMD. Immaturity of fibres, however, needs to be taken into account, especially
      in neonates.

PMID- 15488031
TI  - A quantitative investigation of neuronal cytoplasmic and intranuclear inclusions
      in the pontine and inferior olivary nuclei in multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a sporadic neurodegenerative disease
      characterized by the presence of neuronal and oligodendroglial alpha-synuclein
      aggregates. To investigate the relationship between the occurrence of neuronal
      cytoplasmic and intranuclear inclusions (NCIs and NNIs, respectively) and the
      progression of neuronal degeneration, we performed a quantitative analysis of the
      pontine and inferior olivary nuclei based on 14 cases of MSA. alpha-Synuclein
      immunohistochemistry revealed that NCIs and NNIs were present in both brain
      nuclei in all the cases. The average incidence of NCIs in the pontine and
      inferior olivary nuclei was 9.1% and 25.8%, respectively, and that of NNIs was
      9.2% and 9.0%, respectively. The number of NNIs was strongly correlated with that
      of neurones in the pontine and inferior olivary nuclei. Although the number of
      NCIs was not correlated with the neuronal population in both nuclei, the NCI
      count in patients with moderate MSA was higher than in patients with mild MSA.
      The NNI count was much higher than the NCI count in the pontine nucleus in four
      patients, and was the same in the olivary nucleus in three of the four patients.
      Moreover, the neuronal population in the NNI-predominant cases was significantly
      higher than in the NCI-predominant cases. These findings suggest that NCI
      formation is accelerated by the progression of the disease process, and that in
      MSA, NNI formation is an earlier phenomenon than NCI formation.

PMID- 15488032
TI  - Identification of up-regulated genes by array analysis in scrapie-infected mouse
      brains.
AB  - The major neuropathological features of the transmissible spongiform
      encephalopathies (TSEs) are well documented, however, the underlying molecular
      events are poorly defined. We have applied cDNA expression arrays and
      quantitative RT-PCR to the study of gene expression in the brain, and more
      specifically in the hippocampus, of the well-characterized ME7/CV mouse model of
      scrapie. The number of genes showing consistent, scrapie-associated changes in
      expression was limited, and was primarily restricted to glial-associated genes.
      Increased expression of genes encoding glial fibrillary acidic protein, vimentin,
      complement component 1q (alpha and beta polypeptides), cathepsin D, clusterin and
      cystatin C was evident in the hippocampus from 170 days after inoculation (dpi),
      with expression increasing thereafter to terminal disease (225-235 dpi).
      Elevation of gene expression preceded clinical disease by approximately 30 days,
      and coincided with a 20-day period in the ME7/CV model during which 50% of the
      CA1 hippocampal neurones are lost. Increased expression of cystatin C, an
      inhibitor of lysosomal cysteine proteases, is a novel finding in the context of
      TSE neuropathology and was confirmed by Western analysis and immunocytochemistry.

PMID- 15488033
TI  - Drawing out leadership.

PMID- 15488035
TI  - Relationship between illness representation and self-efficacy.
AB  - AIM: This paper reports a patient survey exploring the possible relationship
      between illness perception and self-efficacy following a cardiac event, and the
      implications this could have for nursing practice. BACKGROUND: Cardiac
      rehabilitation guidelines endorse the need to improve psychological care;
      suggesting that individualized support will improve the effectiveness of cardiac
      rehabilitation. Surveys, however, continue to identify that psychosocial factors
      are poorly assessed. Illness representation and self-efficacy are two prominent
      research approaches that have been developed as separate foci for the treatment
      of patients. METHOD: A cross-sectional survey with patients diagnosed with either
      myocardial infarction or angina over an 8-month period in two hospitals. The
      Illness Perception Questionnaire, General Self-Efficacy Questionnaire, Cardiac
      Diet Self-efficacy Instrument and Cardiac Exercise Self-efficacy Instrument were
      used, alongside two specifically-designed scales: the Diet Outcome Expectation
      and Exercise Outcome Expectation Scales. RESULTS: The results indicate that there
      is a significant relationship between illness perception and self-efficacy. The
      greater patients' perceived consequences of the heart condition, the lower was
      the general self-efficacy available to cope with the condition. Further, the
      longer the perceived time the condition will affect the patient, the higher the
      specific self-efficacy to maintain a change of diet or exercise regime.
      CONCLUSION: The findings identify that, in the initial phase of recovery, nursing
      practice needs to focus on the key variables of "consequence" and "timeline" in
      order to increase patients' confidence in their ability to cope (self-efficacy).

PMID- 15488036
TI  - Patients' experience of the diagnosis and treatment of skin cancer.
AB  - PURPOSE: This paper describes the experience of being diagnosed with skin cancer
      from the perspective of patients. BACKGROUND: Despite the number of people with
      newly-diagnosed skin cancer increasing each year, the psychological impact of
      receiving such a diagnosis has received little attention. Research in this area
      is sporadic and has predominantly focused on malignant melanoma and used a
      quantitative approach. METHOD: Sixteen patients were interviewed about their
      experiences of being diagnosed with malignant melanoma, basal cell carcinoma or
      squamous cell carcinoma. The interview transcripts were analysed using thematic
      content analysis. FINDINGS: Similar themes for the two non-melanoma forms of skin
      cancer patients emerged. Information and knowledge of skin cancer appeared as a
      key theme, and influenced experiences in a variety of different ways. Patients
      with malignant melanoma recounted similar experiences to those with basal cell
      carcinoma or squamous cell carcinoma. People with malignant melanoma, however,
      used a wider variety of strategies in order to cope with the diagnosis.
      Satisfaction with the care experienced by each of the three groups played a
      crucial role in minimizing the experience for the patients. CONCLUSIONS: Patients
      with skin cancer should not be conceived as a homogeneous group, but one in which
      there are a number of diagnoses which differ in prognosis, and so may result in a
      variety of different consequences and thus experiences for patients.

PMID- 15488037
TI  - Nursing competencies for spiritual care.
AB  - AIM: This paper aims to answer the question: What competencies do professional
      nurses need to provide spiritual care? BACKGROUND: Nursing literature from The
      Netherlands shows little clarity on the qualities that nurses require to provide
      spiritual care. Although the international literature provides some practical
      guidance, it is far from conclusive on the required qualities of nurses. METHOD:
      A qualitative literature review was conducted to draw together information from
      the nursing literature in order to formulate nursing competencies. A format
      developed for higher nursing education in The Netherlands was used; this consists
      of description of a general domain, specific competencies, vignettes, key focus
      and objectives. RESULTS: The resulting competency profile has three core domains
      (awareness and use of self, spiritual dimensions of the nursing process, and
      assurance and quality of expertise) and six core competencies (handling one's own
      beliefs, addressing the subject, collecting information, discussing and planning,
      providing and evaluating, and, integrating into policy). DISCUSSION: Spirituality
      is a field in nursing that is still in its infancy. CONCLUSION: This literature
      review yields a competency profile that may help to structure future care,
      research and education in spiritual care by nurses. Implications of the work for
      future research and education are discussed.

PMID- 15488038
TI  - Central venous catheters: a survey of ICU practices.
AB  - AIM: This paper describes the current infection control practices for CVC care
      and compares these to evidence-based practice guidelines. BACKGROUND: Intensive
      care patients with central venous catheters (CVCs) are at risk of catheter
      related infection, which increases morbidity, mortality and health care costs.
      Infection control practices, including care of intravenous administration sets
      and catheter sites, are undertaken by nurses in an attempt to avoid infection.
      Although practice guidelines are available, infection control practices may vary
      between practitioners and institutions; however, current practice has not been
      formally surveyed. METHOD: A prospective, cross-sectional descriptive survey was
      carried out. Intensive care units (n = 14) in Australia were surveyed about their
      infection control policies for CVC care. Results were tabulated and compared with
      evidence-based practice guidelines. RESULTS: A wide variety of responses was
      received about duration of administration set use for standard, parenteral
      nutrition and propofol (lipid-based anaesthetic) infusions; ad hoc administration
      set connection technique; dressing frequency, materials and solutions; and
      barrier precautions used during procedures. There was inconsistent adherence to
      the guidelines. CONCLUSION: There is variation in the infection control approach
      to CVC care. Greater adherence to existing Centers for Disease Control Guidelines
      would assist in the standardization of best practice and facilitate evidence
      based care.

PMID- 15488039
TI  - The struggle for sanitary reform in the Lancashire cotton mills, 1920-1970.
AB  - AIM: This paper reports one aspect of a larger study. The aim of this aspect was
      to explore the role of the "welfare officer" in promoting the health of cotton
      mill workers during this period. BACKGROUND: The paper considers one element of a
      broad exploratory study of the health of women cotton mill workers in the North
      West of England. The original purpose of the study, which was conducted in 2002
      in two towns, Oldham and Ashton-under-Lyne, was to explore the women's own
      perceptions of the impact of their work on their health, and to find out what, if
      any, help and support they obtained. During the course of the study it was
      discovered that "welfare officers", some of whom were trained nurses, had an
      important role in promoting the health of these workers. The study was therefore
      expanded to incorporate data obtained directly from interviews with a small
      sample of welfare officers. The present paper focuses on the issue of sanitary
      reform and considers the role of the "welfare officer" in promoting public health
      in the workplace. METHODS: The study employed a combination of archive searches
      and oral history interviewing. In total, 31 interviews were undertaken between
      June 2001 and October 2002. The interpretive process focussed both on the
      ideological power structures which influenced the perspectives of participants,
      and on evidence for those aspects of participants' experiences which impacted on
      their health. FINDINGS: In considering their health, female cotton-mill workers
      recalled that the poor sanitary conditions in their workplaces during the middle
      years of the 20th century had been a source of some concern to them. They also
      observed that mill welfare officers took a hand in promoting improvement in
      available facilities. Welfare officers themselves recounted their own concern
      regarding the poor sanitary conditions in the mills, and their efforts to improve
      conditions for the mill workers. CONCLUSIONS: The paper demonstrates the role of
      a little-known group of health workers in the middle years of the 20th century,
      and demonstrates the importance of oral history work in re-capturing elements of
      nursing work and experience, which do not appear extensively in the written
      record. The study's relevance to contemporary practice lies in the insight it
      offers into the autonomy with which these occupational health workers defined
      their roles and performed their work.

PMID- 15488040
TI  - Glass contamination in parenterally administered medication.
AB  - AIM: This paper reports a study examining glass particle contamination in two
      ampoule sizes under three different experimental conditions (n = 18 in each
      group). BACKGROUND: While existing literature is clear that glass contamination
      occurs on opening single-dose glass ampoules, the clinical significance of
      intramuscular administration of glass particles is equivocal. Current nursing
      practice standards do not adequately address this issue in terms of aspiration or
      filtration techniques that can minimize risk to patients. METHODS: A computer
      microscope was used to compare the number and size of glass particles aspirated
      into a syringe between two needle sizes [18 gauge (G) (130 microm lumen diameter)
      and 21 gauge (90 microm lumen diameter)] without filters and 19G (110 microm
      lumen diameter) filtered needles. Data were collected in 2002. RESULTS: At least
      one glass particle was found in 22% of the 1-mL ampoules, and 56% and 39% of the
      2-mL ampoules, using 18G and 21G needles, respectively, had glass contaminants.
      Many of the 2-mL ampoules produced multiple glass particles on opening. Use of
      19G filtered needles resulted in no glass particles. There was a significant
      difference in mean particle size between the 18G and 21G groups of 2-mL ampoules.
      CONCLUSION: Our results support the existing literature in that larger bore
      unfiltered needles increased the risk of aspirating more glass and other
      particles than smaller bore or filter needles. These data add further support to
      the use of filtered needles in administering IM medications to patients who
      receive ongoing scheduled IM injections.

PMID- 15488041
TI  - Application of systematic review methods to qualitative research: practical
      issues.
AB  - AIM: This paper explores practical methodological issues which arise from the
      application of systematic review and meta-synthesis techniques to qualitative
      research studies in the context of a pragmatic health services research question.
      BACKGROUND: The emphasis on, and volume of, qualitative research is increasing.
      As a result, there is a need to integrate and disseminate qualitative research
      findings. However, relatively little has been written about the methodology of
      systematically reviewing and meta-synthesizing qualitative research studies, and
      about the practical issues which arise in the course of these processes. METHODS:
      A systematic review and meta-synthesis was undertaken of qualitative research
      studies reporting data relevant to the pragmatic health services research
      question: "What factors facilitate or impede role development and/or effective
      practice as a clinical nurse specialist, nurse practitioner, advanced nurse
      practitioner or consultant nurse based in acute hospital settings?" FINDINGS: The
      identification of relevant studies is substantially more time-consuming than the
      identification of relevant studies for a systematic review of randomized
      controlled trials. A substantially larger proportion of papers has to be
      retrieved for full reading. Articles with unclear titles which lack abstracts
      cannot be dismissed as irrelevant. Study appraisal and data analysis, being
      iterative processes, are also more time-consuming than the appraisal and meta
      analysis of quantitative studies. It may be possible to reduce the frustrations
      inherent in the distance between the reviewer and the participants in the primary
      research by using full project reports rather than published articles.
      CONCLUSIONS: Conducting a systematic review and meta-synthesis of qualitative
      research studies is a rewarding but demanding activity, and adequate time and
      resources must be made available. Some recommendations are made which may
      facilitate those processes.

PMID- 15488042
TI  - Assessing mothers' concerns in the postpartum period: methodological issues.
AB  - AIM: This paper reports a study evaluating the sensitivity of a semi-structured
      interview schedule and card sort methods in assessing postpartum concerns of
      women. BACKGROUND: Several methods have been used to assess postpartum maternal
      concerns and the process of becoming a mother, but few studies have evaluated the
      methods with respect to their sensitivity for obtaining information. METHOD: A
      cohort of mothers was followed-up at one (n = 110) and 6 weeks (n = 83) after
      childbirth in Dar es Salaam, Tanzania. Women with a minimum of 7 years of primary
      education were interviewed and they also sorted cards. Those with less fewer than
      7 years of primary education were interviewed only. The methods were used in
      alternate order to assess method interaction. RESULTS: In the interviews at 1
      week, mothers more often expressed worry and interest related to the baby or
      themselves when they had sorted cards first. The extent to which women expressed
      worry and interest about specific baby- and mother-related topics was generally
      higher for women who had sorted cards before the interview at both 1 and 6 weeks.
      Independent of whether they were interviewed only, interviewed after sorting
      cards or before, mothers more often expressed a higher degree of interest than of
      worry about the baby and self at both 1 and 6 weeks. The order of the data
      collection methods did not influence the way women sorted cards as being worries
      and interests. CONCLUSION: Compared to interview using a semi-structured
      interview schedule, our findings suggest that the card sort is more sensitive in
      obtaining information about women's concerns. Although the interview method has
      the advantage of reaching less educated people, the card sort is a technique that
      is associated with fewer barriers and is a more participatory method for those
      who can use it.

PMID- 15488043
TI  - An assessment form for clinical nursing education: a Delphi study.
AB  - AIM: This paper reports a study to develop further the existing assessment form
      and to capture new aspects of assessment for the nursing profession of the future
      for inclusion in the form. BACKGROUND: Since nursing education became part of the
      higher education system, the assessment of clinical periods of the programme has
      become more complicated and requirements are more demanding. Changes in the
      health care sector, such as demographic changes and shorter hospitalization,
      create demands upon the independent nursing role of the future. Many educational
      documents, such as an assessment form, must continuously be up-dated and adapted
      to changes in society. METHOD: A Delphi study concerning the content of this
      assessment form was carried out using two rounds. Through this process, an expert
      panel gave their opinions about the form and possible changes to it. RESULTS:
      There was general acceptance of the content in the current assessment form.
      Suggested changes were the addition of two factors concerning collaboration with
      the family and society, and development of the student's independence. Two new
      area headings were suggested: one about ability to use the nursing process, and
      the other about development of a professional stance. CONCLUSIONS: The suggested
      changes in the assessment form match expected changes in the health care sector
      and the demands of an academic nursing education.

PMID- 15488044
TI  - Nursing students' beliefs about poverty and health.
AB  - PURPOSE: This paper examines baccalaureate nursing students' beliefs about the
      relationship between poverty and health, and the factors that influence these
      beliefs. BACKGROUND: The relationship between poverty and health is well
      established, and poverty remains a persistent problem in many industrialized
      nations. Nurses' understanding of how poverty influences health will affect how
      they interact with individual clients as well as the strategies they employ to
      address poverty-related issues. No studies have examined nursing students'
      understandings of how poverty influences health and the factors that influence
      that understanding. METHODS: A cross-sectional survey of a random sample (n =
      740) of basic baccalaureate nursing students was conducted in three Canadian
      universities in 2000. Students completed a 59-item questionnaire eliciting data
      on demographic variables, personal and educational exposure to poverty, beliefs
      about the relationship between poverty and health (myth, drift, behavioural,
      structural), and attitudes to poverty. RESULTS: Students were most likely to
      adhere to a structural explanation of the relationship between poverty and
      health. Very little of the variance in myth and drift explanations was accounted
      for by course or personal exposure, programme level, age, and attitudes toward
      poverty. Greater course exposure and more positive attitudes toward the poor
      predicted support for the structural explanation. Support for the behavioural
      explanation was influenced by attitudes toward the poor and, to a lesser extent,
      by course exposure, age, and programme level. CONCLUSION: Students would benefit
      from greater exposure to poverty through coursework that emphasizes the
      structural factors contributing to poverty and its negative health consequences.
      Classroom experience should be complemented with clinical placements that provide
      students with opportunities to interact with families living in poverty and to
      work collaboratively with others to address the causes and consequences of
      poverty at community and policy levels.

PMID- 15488045
TI  - A patient's response to Theobald K. & McMurray A. (2004) Coronary artery bypass
      surgery: discharge planning for successful recovery. Journal of Advanced
      Nursing47(3), 483-491.

PMID- 15488046
TI  - Measles deaths drop dramatically as vaccine reaches world's poorest children.

PMID- 15488049
TI  - Routine pre-oxygenation - a new 'minimum standard' of care?

PMID- 15488050
TI  - Critical care rosters and workload.

PMID- 15488051
TI  - Left ventricular mechanical performance in elderly patients after induction of
      anaesthesia. A comparison of inhalational induction with sevoflurane and
      intravenous induction with fentanyl and propofol.
AB  - We investigated changes in left ventricular mechanical performance in 40 patients
      aged > 70 years in whom anaesthesia had been induced with sevoflurane or with
      fentanyl and propofol. The ratio of ventricular contractility to arterial
      properties, which reflects left ventricular performance, was estimated from the
      ratio of ventricular end-systolic elastance to effective arterial elastance. This
      ratio decreased after induction in both groups, the magnitude of the decrease
      being significantly greater in the fentanyl/propofol group than in the
      sevoflurane group. Decreases in mean arterial pressure after induction of
      anaesthesia in the two groups were similar, whereas the magnitude of the decrease
      in heart rate in the sevoflurane group was greater than that in the
      fentanyl/propofol group. Sevoflurane may therefore be preferable to fentanyl and
      propofol for induction of anaesthesia in elderly patients because of its lesser
      effect on left ventricular performance.

PMID- 15488052
TI  - Effect of propofol and isoflurane anaesthesia on the immune response to surgery.
AB  - There are two major subpopulations of peripheral helper T lymphocytes: T helper 1
      (Th1) and T helper 2 (Th2) cells. Surgical stress increases the number of Th2
      cells, and decreases that of Th1 cells, resulting in a decrease in the Th1/Th2
      ratio, and, consequently, in suppressed cell-mediated immunity. Since anaesthesia
      can suppress the stress response to surgery, it may inhibit the decrease in the
      Th1/Th2 ratio. Using flow cytometry, we studied whether propofol anaesthesia (n =
      9) or isoflurane anaesthesia (n = 9) had more effect on the decrease in the
      Th1/Th2 ratio after surgery in patients undergoing craniotomy. The Th1/Th2 ratio
      decreased significantly after isoflurane anaesthesia (p = 0.011), while it did
      not change after propofol anaesthesia. The ratio was significantly lower with
      isoflurane than propofol (p = 0.009). Propofol anaesthesia attenuated the
      surgical stress-induced adverse immune response better than isoflurane
      anaesthesia.

PMID- 15488053
TI  - A National Survey of ICU consultant working practices at weekends.
AB  - A questionnaire was sent to all Intensive Care Society linkmen to investigate
      weekend working arrangements on Intensive Care Units (ICU) in the United Kingdom.
      In all, 87 responses revealed that the average consultant covering ICU at
      weekends works a 1 in 6 rota, is responsible for 10 beds, works 8-9 h a day and
      receives two calls at night. Of consultants, 54% cover anaesthesia as well as
      ICU, 55% work a 48 h or 72 h weekend and only one in five consultants currently
      have fixed sessional allocation for weekend working. 83% felt that they should
      not cover anaesthesia as well as ICU and there was no support for consultants to
      be resident at night. Applying the terms and conditions of the new consultant
      contract for England to this average consultant would result in 6.6 Programmed
      Activities for the weekend and 2 days of compensatory rest.

PMID- 15488054
TI  - Non-invasive ventilation in surgical patients in a district general hospital.
AB  - We have retrospectively audited the use of non-invasive ventilation (NIV) in
      surgical patients. We analysed the case notes of 38 surgical patients who
      received NIV over a 9-month period. Twenty-three patients received NIV following
      emergency surgery, eight after elective surgery, and seven did not have an
      operation. Co-morbidity was common. The commonest reasons for starting NIV were
      chest infection, acute respiratory distress syndrome and pulmonary oedema. NIV
      was often only one aspect of treatment in surgical patients with complex medical
      problems. With intensive support from the critical care outreach team, NIV can be
      safely delivered on a surgical ward, and may sometimes prevent intensive care
      unit admission. Use of NIV on the intensive care unit may obviate the need for
      tracheal intubation in some patients. In very ill surgical patients with a poor
      prognosis, NIV was frequently used as the ceiling of respiratory support.

PMID- 15488055
TI  - The accuracy of trained nurses in pre-operative health assessment: results of the
      OPEN study.
AB  - We quantified the accuracy of trained nurses to correctly assess the pre
      operative health status of surgical patients as compared to anaesthetists. The
      study included 4540 adult surgical patients. Patients' health status was first
      assessed by the nurse and subsequently by the anaesthetist. Both needed to answer
      the question: 'is this patient ready for surgery without additional work-up,
      Yes/No?' (primary outcome). The secondary outcome was the time required to
      complete the assessment. Anaesthetists and nurses were blinded for each other's
      results. The anaesthetists' result was the reference standard. In 87% of the
      patients, the classifications by nurses and anaesthetists were similar. The
      sensitivity of the nurses' assessment was 83% (95% CI: 79-87%) and the
      specificity 87% (95% CI: 86-88%). In 1.3% (95% CI: 1.0-1.6%) of patients, nurses
      classified patients as 'ready' whereas anaesthetists did not. Nurses required
      1.85 (95% CI: 1.80-1.90) times longer than anaesthetists. By allowing nurses to
      serve as a diagnostic filter to identify the subgroup of patients who may safely
      undergo surgery without further diagnostic workup or optimisation, anaesthetists
      can focus on patients who require additional attention before surgery.

PMID- 15488056
TI  - Stability of an epidural analgesic admixture containing epinephrine, fentanyl and
      bupivacaine.
AB  - The addition of epinephrine to solutions containing fentanyl and bupivacaine for
      epidural infusion has been shown to improve the quality of analgesia. However,
      this admixture is not available commercially in the United Kingdom. Moreover,
      stability data applicable to UK practice for this admixture are limited. This
      study investigated the stability of fentanyl 2 microg.ml(-1) plus bupivacaine 1
      mg.ml(-1) in PVC bags with and without epinephrine 2 microg.ml(-1) over a period
      of 184 days both at room temperature and at 4 degrees C. All infusions were found
      to be stable over the study period (> 90% remaining) using stability-indicating
      High Performance Liquid Chromatography (HPLC) methods, with no changes in
      physical appearance or pH (range 4.5-4.2). The infusions were prepared using
      standard pharmaceutical products, so facilitating the batch preparation of
      epinephrine, fentanyl and bupivacaine epidural solutions by hospital pharmacy
      departments.

PMID- 15488057
TI  - A pharmacokinetic study of piroxicam in children.
AB  - Feldene Melt (piroxicam) is commonly used for analgesia following day case
      surgery. The manufacturer's recommended paediatric dose is 0.4 mg.kg(-1) once
      daily. In children, plasma piroxicam levels of 3-5 microg.ml(-1) are associated
      with effective analgesia. However, in adults a single dose of 20 mg piroxicam
      (0.4 mg.kg(-1) for a 50-kg adult) produces plasma levels of only 1.5-2.2
      microg.ml(-1). We therefore studied plasma levels achieved by 0.4 mg.kg(-1) or
      1.0 mg.kg(-1) piroxicam in 22 children aged between 3 and 16 years, undergoing
      elective orthopaedic surgery, in order to investigate the adequacy of single
      dosing. The first 12 patients received 0.4 mg.kg(-1) Feldene Melt pre
      operatively. Following assay of plasma piroxicam levels, a further 10 patients
      received 1.0 mg.kg(-1) Feldene Melt. In both groups, five blood samples were
      taken at 2-hourly intervals. The mean (95% CI) piroxicam level following 0.4
      mg.kg(-1) was 2.90 (2.33-3.54) microg.ml(-1), compared to 5.87 (4.58-7.16)
      microg.ml(-1) following 1.0 mg.kg(-1) (p = 0.0003).

PMID- 15488059
TI  - Vasopressin and terlipressin: pharmacology and its clinical relevance.
AB  - Vasopressin and its analogue, terlipressin, are potent vasopressors that may be
      useful therapeutic agents in the treatment of cardiac arrest, septic and
      catecholamine-resistant shock and oesophageal variceal haemorrhage. The aim of
      this article is to review the physiology and pharmacology of vasopressin and
      summarise its efficacy and safety in clinical trials and its subsequent
      therapeutic use. Recent studies indicate that the use of vasopressin during
      cardiopulmonary resuscitation may improve the survival of patients with asystolic
      cardiac arrest. Vasopressin deficiency can contribute to refractory shock states
      associated with sepsis, cardiogenic shock and cardiac arrest. Low doses of
      vasopressin and terlipressin can restore vasomotor tone in conditions that are
      resistant to catecholamines, with preservation of renal blood flow and urine
      output. They are also useful in reducing bleeding and mortality associated with
      oesophageal variceal haemorrhage. The long-term outcome of the use of these drugs
      is not known.

PMID- 15488058
TI  - Extending low-dose epidural analgesia for emergency Caesarean section using
      ropivacaine 0.75%.
AB  - We compared ropivacaine 0.75% and bupivacaine 0.5% for extending low-dose
      epidural analgesia for emergency Caesarean section, using a prospective double
      blind randomised controlled trial design. The trial was halted after 45 patients
      were studied (23 ropivacaine; 22 bupivacaine) because bupivacaine was replaced by
      levobupivacaine in our unit. Time to reach T4 for loss of cold sensation was
      similar in both groups, although analgesic supplementation was required less
      often in the ropivacaine group than in the bupivacaine group (2/23 vs. 9/21; p =
      0.01).

PMID- 15488060
TI  - Bibliometric analysis of original molecular biology research in anaesthesia.
AB  - Molecular biology has expanded the horizons of anaesthesia during the last 20
      years and has led to an increase of basic science articles that are published in
      the specialised anaesthetic journals or originate in anaesthetic institutions. We
      searched for and analysed the specific features, such as year of publication,
      publishing journal, and country of origin, of all such molecular biology articles
      stored in the MEDLINE database during the period 1986-2002. We identified 1265
      original articles that used molecular biology techniques; 223 (18%) of these
      articles were published in anaesthetic journals and 1042 (82%) articles in 556
      other biomedical journals. While in the late 1980s only a few molecular biology
      articles were published each year by anaesthetic institutions, worldwide this
      number reached approximately 200 basic science articles by the end of 2002. The
      USA clearly dominates the field of anaesthesia with respect to molecular biology
      research with 839 (66%) such articles.

PMID- 15488061
TI  - Emergency cricothyrotomy: a randomised crossover trial comparing the wire-guided
      and catheter-over-needle techniques.
AB  - In a randomised crossover trial, we compared a wire-guided cricothyrotomy
      technique (Minitrach) with a catheter-over-needle technique (Quicktrach).
      Performance time, ease of method, accuracy in placement and complication rate
      were compared. Ten anaesthesiology and 10 ENT residents performed
      cricothyrotomies with both techniques on prepared pig larynxes. The catheter-over
      needle technique was faster than the wire-guided (48 compared to 150 s, p <
      0.001) and subjectively easier to perform (VAS-score 2.1 vs. 5.6, p < 0.001).
      Correct positioning of the cannula could be achieved in 95% and 85%, respectively
      (NS). There was one complication in the catheter-over-needle group compared to
      five in the wire-guided group. We conclude that the wire-guided minitracheotomy
      kit is unsuitable for emergency cricothyrotomies performed by inexperienced
      practitioners. On the other hand, the catheter-over-needle technique appears to
      be quick, safe and reliable.

PMID- 15488062
TI  - A homemade model for training in cricothyrotomy.
AB  - We describe a simple, homemade model for teaching cricothyrotomy. It can easily
      be constructed from materials found in every anaesthetic room and is cheap,
      portable and usable several times before requiring replacement. We also describe
      evaluation of the model in a two-part study. First, 20 anaesthetic trainees, both
      with and without prior experience of percutaneous cricothyrotomy/tracheotomy,
      cannulated the 'trachea' using two percutaneous airway sets (Ravussin jet
      ventilation catheter[VBM] and Mini-Trach II Seldinger[Portex]), then scored the
      model for realism and usefulness for training. Next, 20 further trainees used the
      Mini-Trach II Seldinger on both the homemade model and a commercially available
      cricothyrotomy/tracheotomy trainer (Pharmabotics), scoring both models as before.
      In the first part of the study, trainees found the homemade model a useful
      substitute for practice of percutaneous techniques and teaching. In the second
      part, both models were rated well, with similar scores. The homemade model is an
      easily assembled alternative to more expensive models. Both experienced and
      inexperienced trainees find practising on such models useful.

PMID- 15488063
TI  - The Cardiff paediatric laryngoscope blade: a comparison with the Miller size 1
      and Macintosh size 2 laryngoscope blades.
AB  - The Cardiff paediatric laryngoscope blade is a single blade that has been
      designed for use in children from birth to adolescence. This open, randomised,
      crossover study compared the Cardiff blade with the straight, size 1, Miller
      laryngoscope blade in 39 infants under 1 years of age and the curved, size 2,
      Macintosh blade in 39 children aged 1-16 years. The same laryngoscopic view was
      obtained with the Cardiff and Miller blades in 26 patients; the view was better
      with the Cardiff blade in seven patients and better with the Miller blade in six
      (median (IQR [range]) grade of laryngoscopy 1 (1-2 [1-3]) vs. 1 (1-2 [1-3]),
      respectively; p = 0.405). The Cardiff blade was faster at gaining a view than the
      Miller blade (mean (SD) time 8.5 (2.9) s vs. 10.2 (3.5) s, respectively; 95% CI
      for difference -2.8 to -0.4; p = 0.009). The Cardiff and Macintosh blades
      produced the same view in 32 patients; the view was better with the Cardiff blade
      in seven patients (median (IQR [range]) grade of laryngoscopy 1 (1-1 [1-3]) vs. 1
      (1-2 [1-3]), respectively; p = 0.008). There was no difference in time to gain
      these views: mean (SD) 8.7 (3.0) s vs. 9.3 (2.7) s, respectively (95% CI for
      difference -1.58 to 0.40; p = 0.237). The Cardiff paediatric laryngoscope blade
      compares favourably with these two established laryngoscope blades in children.

PMID- 15488064
TI  - Thyroid storm prior to induction of anaesthesia.
AB  - A 53- year-old woman without a previous history of thyroid disease was scheduled
      for mastectomy. On arrival in the operating theatre unpremedicated she appeared
      restless and tachycardic. Midazolam and fentanyl was administered intravenously.
      Concomitantly, sinus tachycardia developed and a flush reaction was observed in
      the skin of the thoracic region and neck. The blood pressure increased to 265/160
      mmHg and the patient lost consciousness and became apnoeic. Unconsciousness and
      apnoea lasted for approximately 25 min and the operation was postponed. Further
      investigations revealed an elevated serum free thyroxine level and suppressed
      serum thyrotropin diagnostic of hyperthyroidism. The serum TSH receptor antibody
      concentration was elevated, indicating that the patient was suffering from
      Graves' disease. We present a case of a previously unknown hyperthyroid patient,
      with breast cancer, presenting as a thyroid crisis on induction of anaesthesia.
      Although being quite a rare occurrence, unsuspected thyroid disease should be
      borne in mind when an agitated patient enters the operating theatre.

PMID- 15488065
TI  - Ultrasound guidance for a lateral approach to the sciatic nerve in the popliteal
      fossa.
AB  - Descriptions of the use of ultrasound for nerve location have focused on upper
      limb blocks. We present a case in which ultrasound imaging was used for a lateral
      approach to the sciatic nerve in the popliteal fossa. Ultrasound images taken
      proximal to the popliteal crease showed tibial and common peroneal nerves as
      round hyperechoic structures superficial and lateral to the tibial artery. Under
      direct ultrasound guidance, we placed a block needle close to the tibial nerve
      and confirmed its position with nerve stimulation. Injected local anaesthetic was
      seen on ultrasound as it spread around both tibial and common peroneal nerves.

PMID- 15488066
TI  - Precautions against infection from anaesthetic procedures.

PMID- 15488067
TI  - Clearing the cervical spine in polytrauma.

PMID- 15488068
TI  - Thoracic paravertebral blockade.

PMID- 15488069
TI  - Emergency airway access equipment.

PMID- 15488070
TI  - Respiratory obstruction secondary to laryngeal mask failure.

PMID- 15488071
TI  - Intra-operative 'hypertensive crisis' due to faulty transducer.

PMID- 15488072
TI  - Anaesthesia after cleft palate repair.

PMID- 15488073
TI  - Monitoring seizures with the Bispectral index.

PMID- 15488074
TI  - International Colour Coding for syringe drug labels: a survey.

PMID- 15488075
TI  - The double 'tails-up' capnograph.

PMID- 15488076
TI  - Incompatibility of defibrillators and electrode pads.

PMID- 15488077
TI  - Sleep deprivation and performance.

PMID- 15488078
TI  - Correct positioning of feeding tubes.

PMID- 15488083
TI  - Close physical contact of the heart with diaphragm causes pseudo-asynergy of left
      ventricular inferior wall in normal subjects.
AB  - Paradoxical outward movement of left ventricular (LV) inferior wall in systole is
      occasionally recognized in normal subjects and clinically important in terms of
      the differential diagnosis between physiological pseudo-asynergy and pathological
      asynergy. In this study, the potential mechanisms by which pseudo-asynergy of LV
      inferior wall (PLI) is observed in normal subjects were investigated. PLI was
      defined as the outward movement of LV inferior wall observed during more than 50%
      of systole. The incidence of PLI was evaluated in 7843 consecutive subjects in
      routine echocardiography. The effects of body position and artificial gravity on
      the manifestation of PLI were also examined. PLI was observed in 0.11% (9/7842)
      of subjects on left lateral position. Measurement of the angle formed by LV long
      axis and the long-axis of the body on frontal plane revealed that hearts in
      subjects with PLI were in relatively horizontal position. PLI was observed on
      sitting position in 43% (40/92) of subjects without PLI on left lateral position.
      The subjects with sitting position-induced PLI exhibited significantly higher
      obesity index. PLI was also induced by artificial gravity in 67% (14/21) of
      healthy volunteers on supine position, and the degree of PLI correlated with the
      intensity of gravity. Although the incidence of PLI in routine echocardiography
      is relatively low, PLI can be induced in normal subjects by any condition that
      causes close contact of LV inferior wall to diaphragm. Thus, PLI should be taken
      into consideration in the differential diagnosis of abnormal LV inferior wall
      motion, especially when performing exercise echocardiography.

PMID- 15488084
TI  - High prevalence of isovolumic relaxation flow in healthy subjects.
AB  - BACKGROUND: Inhomogenous left ventricular activation-inactivation has been
      suggested to play a role in the genesis of segmental early relaxation and in turn
      of isovolumic relaxation flow (IRF). The spatial distribution of conduction
      system in the left ventricle leads to heterogenous activation sequence even in
      healthy subjects. This study was conducted to evaluate our hypothesis that IRF
      should be ubiquitous in healthy subjects. METHODS: This prospective study
      included 126 healthy subjects (aged 15-81 years) free of acute or chronic illness
      by history and physical examination. No significant abnormality appeared in the
      resting 12-lead electrocardiogram or transthoracic echocardiogram. With the
      pulsed-wave Doppler echocardiography, the sample volume was placed at the mid
      ventricle to detect the IRF. RESULTS: An apically directed IRF, with the velocity
      17-101 cm/sec and the duration 57-145 ms, could be detected in all the study
      subjects. There was no inter-sex difference in such characteristics of IRF.
      However, its duration and velocity got longer and higher with aging. The
      fractional shortening of the left ventricle and the interventricular septal
      thickness were stepwisely selected as the determinants of the IRF velocity, and
      the transmitral E-to-A wave velocity ratio, the left ventricular inflow
      propagation velocity, and the interventricular septal thickness as the
      determinants of the IRF duration. CONCLUSIONS: IRF is ubiquitous in healthy
      subjects. Both the duration and the velocity of IRF present an aging trend and
      may be mainly related to left ventricular diastolic and systolic performance,
      respectively.

PMID- 15488085
TI  - Maximal longitudinal contraction velocity in assessment of left ventricular
      systolic function: a pulsed tissue Doppler and M-mode study.
AB  - AIMS: During recent years the maximal longitudinal contraction velocity (MLCV),
      measured by either pulsed tissue Doppler or M-mode, has been suggested as an
      index of left ventricular (LV) systolic function. The aims of the present study
      were to compare MLCV with ejection fraction (EF) in consecutive patients with
      known or suspected heart failure and to compare measures from recordings by
      pulsed tissue Doppler with recordings by M-mode. METHODS AND RESULTS: Sixty-four
      consecutive patients with suspected or known heart failure, referred to
      echocardiography, were included. Twelve of these patients had decreased LV
      systolic function defined as EF < 50% calculated by the biplane Simpson's rule,
      while a significantly (P > 0.05) higher proportion of 23 had decreased function
      defined as decreased MLCV recorded by pulsed tissue Doppler. Measures from M-mode
      recordings were significantly lower (P < 0.001) than the corresponding measures
      from tissue Doppler recordings. CONCLUSIONS: The study shows that higher values
      of MLCV are obtained by pulsed tissue Doppler than by M-mode. Reference values
      can therefore not be used interchangeably. The results also suggest that MLCV is
      a more sensitive index of LV systolic function than EF.

PMID- 15488086
TI  - Analysis of left atrial volume change rate for evaluation of left ventricular
      diastolic function.
AB  - An excellent correlation exists between the change in the left atrial (LA)
      angiographic area and posterior aortic wall motion. The aim of the study was to
      define the role of posterior aortic wall motion, indicating LA volume change,
      during the left ventricular (LV) phase for the assessment of LV diastolic
      function. A total of 155 patients underwent echocardiography after cardiac
      catheterization. Study patients were classified into four groups according to the
      ratio of early-to-late transmitral flow velocity (E/A ratio) and/or LV end
      diastolic pressure (EDP): 42 patients with LVEDP < 15 mmHg and E/A ratio > 1
      (normal filling); 46 patients with E/A < 1 (impaired relaxation); 46 patients
      with LVEDP > or = 15 mmHg and E/A > 1 and < 2 (pseudonormal filling); 21 patients
      with E/A > 2, E > or = 70 cm/s, and E-wave deceleration time < or = 160 ms
      (restrictive filling). The slopes of early and late (slopes E and A) diastolic
      motion of LA wall were derived from M-mode analysis, together with the LV
      isovolumic time constant Tau from cardiac catheterization. Values of slope E/A
      decreased in restrictive filling, pseudonormal filling, and impaired relaxation
      as compared with normal filling (0.41 +/- 0.14, 0.69 +/- 0.15, and 0.56 +/- 0.23
      vs 1.25 +/- 0.26, P < 0.001, respectively) and correlated inversely with the
      isovolumic time constant Tau (r = 0.79, P < 0.001). In cases for which a value of
      slope E/A < 1 was obtained, indicating a relaxation abnormality, the M-mode
      derived pattern of LA wall motion identified the underlying abnormal LV diastolic
      function with a sensitivity of 98.3%, a specificity of 100%, a positive
      predictive value of 100%, and a negative predictive value of 95.2%. Analysis of
      the slope of LA wall motion, indicating LA volume change rate, during LV
      diastolic phase is useful in evaluating LV diastolic function. It provides a new
      noninvasive index that correlates well with invasive index of LV relaxation.

PMID- 15488087
TI  - Safety of dobutamine stress transesophageal echocardiography in obese patients
      for evaluation of potential ischemic heart disease.
AB  - The purpose of this study was to determine the safety of dobutamine stress
      transesophageal echocardiography (DS-TEE) in the evaluation of potential coronary
      artery disease in obese patients. Obese patients tend to have a higher prevalence
      of hypertension, coronary artery disease, and sleep apnea conditions that could
      potentially predispose to complications during endoscopic procedures such as DS
      TEE. In addition, obese patients are more likely to have oxygen desaturation
      during upper gastrointestinal endoscopy. Thus, the safety of DS-TEE in 90 obese
      patients (body mass index (BMI) > or = 27.5 kg/m2) and 86 nonobese patients (BMI
      < 27.5 kg/m2) was compared. Minor complications (i.e., complications of transient
      duration and requiring no or only simple intervention) occurred with almost equal
      frequency in the nonobese and obese groups (28% vs. 29%, P = ns). Transient
      hypotension was observed in 9% of the obese group compared to 22% in the nonobese
      group (P < 0.025). However, transient hypertension was noted in 20% of the obese
      patients compared to 6% in the nonobese group (P < 0.01). A major complication
      occurred in three obese patients (3.3%), which included hypotension, marked
      elevation of systolic blood pressure, or ventricular fibrillation. Four patients
      (4.7%, P = ns) of the nonobese group had a major complication, which included
      sustained ventricular tachycardia in one, hypertension in one, and hypotension in
      two patients. No deaths occurred in either group. Although obesity should remain
      a consideration in the risk assessment of whether or not to perform DS-TEE, when
      proper precautions are instituted DS-TEE appears equally safe in obese as
      compared to nonobese patients.

PMID- 15488088
TI  - A rare cause of reversible dilated cardiomyopathy: hypocalcemia.
AB  - Hypocalcemia is a rare cause of reversible heart failure. We reported a 40-year
      old woman who had severe heart failure resistant to the usual antifailure
      therapy. She had severe hypocalcemia due to hypoparathyroidism after strumectomy.
      Echocardiography showed a large left ventricle with very low ejection fraction of
      25% and moderate mitral regurgitation. After supplementation of calcium and
      vitamin D, her clinical situation and hemodynamics improved rapidly. At 15
      months, myocardial impairment resolved fully. In conclusion, hypocalcemia should
      be considered in the differential diagnosis of resistant severe heart failure.

PMID- 15488089
TI  - Hemodynamic instability after receiving intravenous Perflutren for contrast
      echocardiography in an elderly female.
AB  - Myocardial contrast echocardiography (MCE) has been used with increasing
      frequency and is considered a safe way to improve left ventricular border
      opacification. Studies have consistently documented that MCE can improve the
      ability to assess both global and regional left ventricular function by
      echocardiography. We report the case of an 83-year-old female who developed
      immediate and sustained hemodynamic instability after the injection of Perflutren
      for a contrast echocardiogram. We reviewed the literature and found no such
      previous reactions with Perflutren. Based on the temporal sequence of hypotension
      following Perflutren injection along with other clinical data, we concluded that
      our patient's hemodynamic instability was most likely secondary to an
      anaphylactic reaction.

PMID- 15488090
TI  - Transesophageal investigation of surgically ligated left atrial appendage.
AB  - Surgical ligation of the left atrial appendage is often performed during heart
      surgery for various diseases like mitral prosthesis implantation, mitral valve
      repair, and even coronary artery revascularization, mainly to prevent thrombus
      formation and systemic embolism in patients with atrial fibrillation. However
      surgical ligation is sometimes incomplete, thereby exposing the patient to
      residual embolic risk. We report two cases of surgical ligation of the left
      atrial appendage focusing on the transesophageal echographic aspects of complete
      or incomplete closure of the appendage.

PMID- 15488091
TI  - Left atrial mass: thrombus mimicking myxoma.
AB  - A 31-year-old woman underwent elective transthoracic echocardiography for
      paroxysmal atrial fibrillation, which showed a large left atrial mass. A two
      dimensional echocardiogram showed a large left atrium mass. Subsequent
      transesophageal echocardiography showed a 3 cm x 3 cm circular mass with smooth
      contours. The differential diagnosis included myxoma versus thrombus, but because
      of morphology and mobility of the mass, it was difficult to differentiate one
      from the other. The patient had been on chronic coumadin therapy for paroxysmal
      atrial fibrillation. An operation was performed and the intracardiac mass
      resected. On pathologic examination the mass was diagnosed as an organized
      thrombus. A brief review of the literature has been presented to discuss the
      differential diagnosis of the mass in the left atrium.

PMID- 15488092
TI  - Large atrial appendage thrombus in the presence of severe mitral regurgitation:
      contradictory hemodynamics or expected findings.
AB  - A case of a large left atrial appendage thrombus in the presence of severe mitral
      regurgitation is presented. The use of transesophageal echocardiography in this
      setting was not only useful but also crucial despite the low anticipated
      diagnostic yield given the expected altered left atrial flow dynamics from the
      turbulent regurgitant lesion. However, additional confounding factors could have
      acted as potential mechanisms to enhance thrombosis in this setting and
      consequently are discussed.

PMID- 15488093
TI  - Survival to the age of 52 years in a man with unrepaired tetralogy of Fallot.
AB  - Tetralogy of Fallot is the most common cyanotic congenital heart defect during
      infancy. It is composed of a ventricular septal defect, an overriding aorta,
      obstruction of right ventricular outflow, and right ventricular hypertrophy. Most
      patients experience cyanosis at birth and die in childhood without surgical
      intervention. The rate of survival at 40 years without surgical correction is
      only 3%. We present the case of a man with tetralogy of Fallot who survived until
      the age of 52 years without surgical intervention.

PMID- 15488094
TI  - Right atrial aneurysm in adults--report of three cases and review of literature.
AB  - Right atrial aneurysm (RAA) or RA diverticula are described as saccular
      structures originating from the RA free wall. This must be differentiated from
      aneurysmal dilation of the entire right atrium. We diagnosed three cases of RAA
      since 2000. The first patient presented with effort intolerance, the second with
      recurrent palpitations, and the third was totally asymptomatic. In all the cases
      transthoracic echocardiography was definitive with little additional information
      obtained from catheterization. We report our experience and review the literature
      pertaining to adult presentation of this interesting pathology, of which only 20
      cases have thus far been reported.

PMID- 15488095
TI  - Aneurysm of sinus of Valsalva dissecting into interventricular septum: a late
      complication of aortic valve replacement.
AB  - A 43-year-old man who had a Carbomedics prosthetic aortic valve replacement in
      1997 was admitted to our hospital with complaints of shortness of breath and
      dyspnea on exertion in 2000. The patient was hospitalized due to atrioventricular
      (AV) complete block and a permanent pacemaker was implanted. At that time
      echocardiography indicated an aneurysm at the left sinus of Valsalva. In 2003,
      the patient was re-admitted to our clinic with complaints of shortness of breath
      and fatigue. Echocardiography showed a sinus of Valsalva aneurysm dissecting into
      interventricular septum. Operation confirmed dissection of the interventricular
      septum and communication between this cavity and the aneurysm of the left sinus
      of Valsalva. The postoperative course was uneventful and the patient was
      discharged in a satisfactory condition. This is the first reported case of
      aneurysm of the sinus of Valsalva dissecting into interventricular septum late
      and complicating aortic valve replacement.

PMID- 15488096
TI  - Morphological assessment of left ventricular thrombus by live three-dimensional
      transthoracic echocardiography.
AB  - We report the usefulness of live three-dimensional transthoracic echocardiography
      (3DTTE) in the morphological assessment of a left ventricular thrombus. Using
      live 3DTTE, the thrombus could be easily viewed end-on and from the sides. In
      addition, by cropping the 3D images sequentially in transverse (horizontal or
      short axis), longitudinal (vertical or long axis), frontal, and oblique planes,
      the degree and extent of lysis within the thrombus, which represents an integral
      part of the clot-resolution process, could be comprehensively assessed. The site
      of attachment of the thrombus in the left ventricular apex and its morphology
      could also be fully evaluated in three dimensions by live 3DTTE.

PMID- 15488097
TI  - Live three-dimensional transthoracic echocardiographic assessment of isolated
      cleft mitral valve.
AB  - We report the usefulness of live three-dimensional transthoracic echocardiography
      in the comprehensive assessment of isolated cleft mitral valve in two adult
      patients studied by us.

PMID- 15488098
TI  - Left ventricular pseudoaneurysm complicating an asymptomatic myocardial
      infarction.

PMID- 15488099
TI  - Patent ductus arteriosus complicated by pulmonary artery endarteritis in an
      adult.

PMID- 15488100
TI  - The Tei index: methodology and disease state values.

PMID- 15488101
TI  - Developing effective evidence-based interventions for adolescents with alcohol
      use disorders.

PMID- 15488102
TI  - The natural history of adolescent alcohol use disorders.
AB  - AIM: To examine clinically relevant research on the development, course and
      outcomes of adolescence alcohol use disorders (AUDs). METHODS: Observational
      studies with adolescent samples were selected for inclusion based on systematic
      assessment of AUDs and clinical relevance. The literature was searched using
      Medline and Psychinfo. Articles on childhood predictors, characteristics, course,
      complications and adult outcomes of adolescent AUDs were reviewed. RESULTS: The
      developmental trajectory toward adolescent AUDs begins with the emergence of
      childhood mental disorders. These problems are transmitted from parent to child
      in a developmentally specific fashion, reflect psychological dysregulation
      dimensions and predict adolescent AUDs. While most DSM-IV AUD diagnostic
      criterion items are valid for adolescents, tolerance and impaired control items
      are problematic, and some adolescents with significant alcohol problems are not
      identified by this diagnostic system. Understanding the psychosocial and
      biomedical complications that accompany AUDs requires attention to factors other
      than alcohol involvement itself, including childhood maltreatment and comorbid
      psychopathology. While some adolescents with AUDs manifest chronic alcohol
      dependence in adulthood, a substantial proportion overcome alcohol problems and
      transition to abstinence or normative drinking. CONCLUSIONS: Developmentally
      specific phenotypic characteristics define the natural history of adolescent
      AUDs, inform clinical assessment and provide the developmental context for
      treatment research. While alcohol consumption may be the primary treatment focus,
      other important consequences, comorbidities and complications need to be
      addressed for successful developmental outcomes to result.

PMID- 15488103
TI  - Salient variables for treatment research of adolescent alcohol and other
      substance use disorders.
AB  - AIMS: To seek a level of uniformity and consistency in the type of data or
      variables collected to allow cross-study comparison and ease in meta-analyses of
      adolescent treatment studies. DESIGN: The rationale for adoption of such a core
      set of variables for adolescent treatment research, the main categories and
      specific types of variables, methods for collecting these variables, including
      the use of specific instruments are reviewed and discussed. FINDINGS: There is a
      relatively small number of adolescent treatment outcome studies. Between studies,
      there are highly variable methodologies, including differences in how outcome or
      treatment success is measured, differences in ascertainment in substance use,
      differences in the measurement of non-substance use variables such as social and
      academic functioning, poor follow-up rates and a lack of comparison groups in
      many studies. CONCLUSIONS: Differences in the types and collection of baseline
      and outcome variables and the need to achieve some level of uniformity across
      adolescent substance use disorders (SUD) treatment studies suggest that
      investigators interested in adolescent treatment outcome research should develop
      a set of 'core variables' that are relatively consistent, or at least comparable,
      across studies.

PMID- 15488104
TI  - Measuring youth outcomes from alcohol and drug treatment.
AB  - AIMS: This report examines adolescent alcohol and drug treatment outcome research
      from a process-oriented, developmental perspective. A dynamic developmental model
      is proposed in which adolescent treatment outcome research incorporate
      considerations relevant to changes occurring typically during this stage of life
      as well as developmental distinctions pertinent to the early onset of abuse and
      dependence. METHOD: Findings from our developmentally focused longitudinal
      research of adolescent treatment participants and the extant literature on
      adolescent treatment outcome are reviewed. Conceptual, research design and
      measurement recommendations are presented from this double developmental
      perspective of addiction. FINDINGS: Techniques for engaging youth in the research
      process, managing confidentiality and facilitating self-disclosure are described.
      Developmental considerations in the type and timing of outcome assessments,
      measurement content, predictor domains and data analytical approaches are
      discussed. Predictors and process measures for adolescent alcohol treatment
      outcome study are suggested based on current findings. CONCLUSIONS: Inclusion of
      developmental considerations may enhance the utility of adolescent treatment
      outcome research.

PMID- 15488105
TI  - Adolescent alcohol misuse: methodological issues for enhancing treatment
      research.
AB  - AIMS: The objective of this article is to present an overview of the current
      state of the field of adolescent alcohol treatment research and to discuss
      several priorities for future research directions. METHOD: The authors identified
      trends in adolescent alcohol treatment research from multiple sources, including
      searches of the National Institutes of Health grantee listings, proceedings from
      annual meetings of the Research Society on Alcoholism and relevant English
      language journal articles available in MEDLINE and PSYCHLIT databases over the
      past decade. RESEARCH RECOMMENDATIONS: This field must build on its major
      strength, which has been its success in appreciating the unique developmental
      characteristics of adolescence and meaningfully incorporating them into
      adolescent alcohol treatment approaches. Priorities for future research include:
      empirically investigating the potential value of harm reduction approaches for
      promoting public health and reducing total harm for adolescents; developing
      efficacious interventions across a wide range of intensities and settings;
      increasing the reach and relevance of randomized treatment efficacy trials and
      their products, with a particular focus on enhancing the recruitment and
      retention of diverse treatment samples; increasing a focus on key individual
      difference variables such as co-occurring diagnoses, that may serve as the basis
      for treatment tailoring; and exploration of the potential benefits of
      transdisciplinary research.

PMID- 15488106
TI  - Motivational enhancement and other brief interventions for adolescent substance
      abuse: foundations, applications and evaluations.
AB  - AIMS: To present a comprehensive review of the use of motivational enhancement
      and other brief interventions for substance use in adolescents. METHODS: In this
      paper, we review the major theoretical foundations and influences of brief
      interventions (including motivational interviewing), consider developmental
      issues in its application for adolescents, discuss methodological issues in the
      design and implementation of brief interventions, including the assessment of
      treatment fidelity, evaluate and interpret the latest findings on brief
      interventions for adolescents and young people and discuss the issue of
      translating and exporting effective research into practice. FINDINGS: Results
      from recent clinical trials using motivational interventions indicate that these
      approaches result in decreases in substance-related negative consequences and
      problems, decrements in substance use and increased treatment engagement, with
      results particularly strong for those with heavier substance use patterns and/or
      less motivation to change. CONCLUSION: While results are promising, more research
      is needed to examine the essential elements of motivational interventions, for
      whom they work best, and their impact on developmental transitions during
      adolescence.

PMID- 15488107
TI  - Family-based therapies for adolescent alcohol and drug use: research
      contributions and future research needs.
AB  - OBJECTIVE: To characterize the developmental status of the family-based
      adolescent alcohol and drug treatment specialty by identifying and discussing
      research and clinical advances. METHOD: Selective and interpretative literature
      review and analysis. STUDY SELECTION: Controlled trials and mechanisms of change
      studies of family-based treatments for adolescent alcohol and drug misuse.
      RESULTS: Clinical innovations of family-based treatments include development of
      detailed therapy, training/supervision, and adherence manuals. Different family
      based treatments have been tested with success in controlled trials and process
      studies. Different versions of the same approach might vary on parameters such as
      treatment dose, setting, and client characteristics. Research advances include
      findings that engagement and retention rates for family-based treatments are
      superior to standard treatment engagement/retention methods. Also, in clinical
      trials in which they are compared with alternative interventions, in the majority
      of studies, family-based treatments produce superior and stable outcomes with
      significant decreases on target symptoms of alcohol and drug use, and related
      problems such as delinquency, school and family problems, and affiliation with
      substance abusing peers. Mechanisms of change studies support the theory basis of
      family-based treatments. For instance, improvements in family interaction
      patterns coincide with decreases in core target alcohol and drug misuse symptoms.
      CONCLUSIONS: Once in the shadows of the adult substance abuse field, the
      adolescent substance abuse specialty has become a unique, clinically creative,
      and empirically-based area. Research and clinical advances of family-based
      treatments have implications for non-family-based interventions in the adolescent
      substance misuse treatment specialty.

PMID- 15488108
TI  - On the learning curve: the emerging evidence supporting cognitive-behavioral
      therapies for adolescent substance abuse.
AB  - AIMS: Cognitive-behavioral therapy (CBT) approaches to intervention for
      adolescent substance use disorders has been limited and formal controlled
      clinical efficacy trials have been rare. Moreover, the early literature on the
      efficacy of CBT for adolescent substance abuse has been characterized by
      significant methodological limitations. Recent innovations in the treatment of
      adolescent substance abuse and the recent completion of several randomized
      clinical trials has brightened the picture with respect to establishing the
      empirical support for CBT. The aim of this review is to integrate the findings
      from controlled trials of CBT for adolescent substance abuse. METHOD: Studies
      representing randomized clinical trials were reviewed using criteria provided by
      Lonigan et al. and Nathan & Gorman as a guide. FINDINGS AND CONCLUSIONS: Despite
      some prominent differences in design and methodology, the studies reviewed
      provide consistent empirical evidence that group and individual CBT are
      associated with significant and clinically meaningful reductions in adolescent
      substance use. The evidence for the efficacy of group therapy is particularly
      important, countering the assertion that aggregating problem youths into group
      treatment settings is associated with iatrogenic effects. The findings from the
      randomized trials reviewed represent significant developments in treatment
      outcome research and lay the foundation for validating CBT for adolescent
      substance use disorders. Future research directions include improving short- and
      long-term outcomes, enhancing treatment motivation and engagement, and
      identifying mechanisms and processes associated with positive change, especially
      for youths with comorbid conditions.

PMID- 15488109
TI  - Implementing school-based substance abuse interventions: methodological dilemmas
      and recommended solutions.
AB  - AIMS: To review current knowledge about the most effective school-based
      interventions for child and adolescent problems, and to present dilemmas and
      potential solutions in mounting and evaluating school-based interventions for
      adolescent alcohol and other drug (AOD) use problems. DESIGN: Two literature
      reviews were conducted: (1) a broad and encompassing review of English-language
      articles published from 1990 to the present concerning school-based interventions
      for child and adolescent problems and (2) an exhaustive review of articles
      concerning Student Assistance Programs, which are the most popular approach to
      school-based AOD intervention in the United States. FINDINGS: Ten key components
      of effective school-based interventions were identified. In addition, six
      pervasive dilemmas in school-based AOD intervention research were discussed.
      Examples of potential solutions to these dilemmas were gleaned from an ongoing
      randomized clinical trial of a Student Assistance Program. CONCLUSIONS: School
      based AOD interventions have several potential advantages over more traditional
      clinic-based AOD interventions. Nonetheless, there are many challenges and
      dilemmas to conducting and evaluating interventions in school settings. With
      patience and guidance, these challenges can be addressed successfully.

PMID- 15488110
TI  - Cross-validation of the alcohol and cannabis use measures in the Global Appraisal
      of Individual Needs (GAIN) and Timeline Followback (TLFB; Form 90) among
      adolescents in substance abuse treatment.
AB  - AIMS: To examine the comparability, reliability and predictive validity of two
      instruments used to assess alcohol use and dependence: the Global Appraisal of
      Individual Needs (GAIN) and the Form 90 Timeline Followback (TLFB) method.
      DESIGN, SETTING AND PARTICIPANTS: Adolescents (n = 101) admitted to a residential
      treatment program in the United States were interviewed at intake with the GAIN,
      and again within a week with a variation of TLFB, called Form 90. Alcohol and
      cannabis measures were compared and used to predict the number of past-month
      substance abuse and dependence symptoms. MEASUREMENT: Self-report measures of
      days of alcohol and cannabis use in the 90 days prior to intake, peak number of
      drinks/joints used, peak blood alcohol content (BAC) and alcohol and cannabis
      abuse and dependence symptom counts. FINDINGS: Results revealed that the measures
      had: (a) excellent comparability (r = 0.7-0.8) across the two instruments; (b)
      deteriorating reliability after reported peak BAC levels exceeded 0.50 and peak
      joints exceeding 19; and (c) similar and strong relationships between use
      measures and the number of abuse/dependence symptoms across measures and
      instruments. CONCLUSIONS: In a sample of 101 adolescents who were admitted to
      residential treatment for alcohol or drug dependence, the corresponding measures
      from the two instruments produced comparable results. If the cross-validation of
      these two measures generalizes to adolescents treated in out-patient settings and
      other adolescent treatment populations, the GAIN and Form 90 may provide useful
      core alcohol measures for meta-analyses.

PMID- 15488111
TI  - Thirty-month relapse trajectory cluster groups among adolescents discharged from
      out-patient treatment.
AB  - AIMS: To identify adolescent relapse trajectory groups following discharge from
      out-patient substance abuse treatment. DESIGN, SETTING AND PARTICIPANTS:
      Adolescents aged 12-18, who were assigned randomly to one of five out-patient
      interventions (n = 563) in four United States communities and followed-up 3, 6,
      9, 12 and 30 months post-intake. OUTCOME MEASURES: Self-report measures of days
      using any alcohol or other drugs (AOD), days of alcohol use, days of cannabis
      use, days of heavy use, days of crack/cocaine use, days of heroin/opiate use,
      days AOD use interfered with responsibilities and days in a controlled
      environment. FINDINGS: Adolescents can be grouped empirically into five relapse
      trajectories over 30 months following out-patient treatment: (a) low AOD use with
      limited days in a controlled environment; (b) low AOD use with high days in a
      controlled environment; (c) moderate/decreasing AOD use; (d) increasing AOD use;
      and (e) consistently high AOD use. CONCLUSIONS: There was considerable
      heterogeneity in the relapse trajectories, varying by the initial response to
      treatment, the stability (versus increase/decrease) of the response and an
      interaction with time in a controlled environment. Cannabis and alcohol were the
      two main substances involved, although the two groups with the poorest
      trajectories had increasing levels of cocaine, opiate and other substance use at
      the 30-month follow-up. This study demonstrates the chronicity of substance use
      even among a subgroup of adolescents and the importance of studying more complex
      longitudinal patterns of recovery.

PMID- 15488112
TI  - Culturally sensitive substance abuse intervention for Hispanic and African
      American adolescents: empirical examples from the Alcohol Treatment Targeting
      Adolescents in Need (ATTAIN) Project.
AB  - AIMS: This study presents preliminary analyses examining the effects of an
      alcohol and other drug use (AOD) intervention with minority juvenile offenders.
      Furthermore, the study investigates the impact of cultural factors on baseline
      AOD use among Hispanic and African American youth, as well as on treatment
      outcome. DESIGN, SETTING AND PARTICIPANTS: Participants were 213 juvenile
      offenders referred for treatment (mean age = 15.7 years), 97 of whom have
      completed treatment to date. The intervention was carried out in clinics placed
      within the neighborhoods in which the participants resided. Intervention Alcohol
      Treatment Targeting Adolescents in Need (ATTAIN) is a controlled clinical trial
      evaluating the effectiveness of a brief motivational, cognitive behavioral
      intervention, guided self-change (GSC). Participants are assigned randomly to the
      individual format of guided self-change (I-GSC), the family involved format of
      guided self-Change (F-GSC), choice of one of these two, or a waiting list control
      condition. Only participants involved in active intervention are included in the
      present report. MEASUREMENTS: Data were collected via structured face-to-face
      interviews. Alcohol and marijuana use measures were collected using the Time-line
      Follow-back interview (TLFB). FINDINGS: There were significant reductions in
      alcohol and marijuana use for all ethnic groups from baseline to post
      intervention. Cultural factors (discrimination, acculturation, ethnic pride and
      cultural mistrust) were associated with pre-intervention levels of alcohol and
      marijuana use. Among Hispanics, pre-intervention level of substance use were
      higher among foreign-born than US-born youth. Analyses conducted with the US-born
      Hispanic group showed that ethnic orientation and ethnic pride were associated
      positively with greater reductions in alcohol use. CONCLUSIONS: The intervention
      provided through ATTAIN appears to be effective with a multi-ethnic population of
      juvenile delinquents. Cultural factors, such as ethnic orientation and ethnic
      mistrust, appear to constitute amenability to treatment factors, with US-born
      Hispanic youth lower in acculturation responding better to the intervention.

PMID- 15488113
TI  - Toward single embryo transfer policy.

PMID- 15488114
TI  - Management of ovarian cysts.
AB  - BACKGROUND: The treatment of an ovarian cyst relies on its nature, and accurate
      preoperative discrimination of benign and malignant cysts is therefore of crucial
      importance. This study was undertaken to review the literature concerning the
      preoperative diagnosis and treatment of ovarian cysts. METHODS: Articles
      concerning ovarian cysts from a medline literature search during the period 1985
      2003 were included in addition to articles found as references in the initial
      publications. RESULTS: Different methods for discriminating between benign and
      malignant ovarian cysts are discussed. The diagnosis and the treatment are
      assessed in relation to age, menopausal status, pregnancy, and whether the cyst
      is presumed to be benign or malignant. In general, expectant management is the
      choice in premenopausal and pregnant women with non-suspicious cysts and normal
      levels of CA-125. In postmenopausal women, unilocular, anechoic cysts less than 5
      cm in diameter together with a normal CA-125 may be followed up. Operation is
      recommended in women with cysts larger than 5 cm and/or elevated levels of CA
      125. Women with symptoms should be operated regardless of age, menopausal status,
      or ultrasound findings. CONCLUSIONS: The preoperative discrimination between
      benign and malignant ovarian cysts is a challenge. Multimodal methods improve the
      results of single modalities, but we still need improved preoperative diagnostic
      tools. Furthermore, these methods should be validated in consecutive patient
      populations large enough to give a reliable estimate of the method's sensitivity
      and specificity.

PMID- 15488115
TI  - Obesity and pregnancy.
AB  - BACKGROUND: As obesity is an increasing problem among fertile women, it is
      crucial that specialists involved in the treatment of these women be aware of the
      risks of complications and know how to deal with them. Complications associated
      with obesity in pregnancy are gestational diabetes mellitus, hypertensive
      disorders, and thromboembolic complications. Complications associated with
      obesity in labor are augmentation, early amniotomy, cephalopelvic disproportion,
      cesarean section, and perioperative morbidity. Complications associated with
      obesity in children are macrosomia, shoulder dystocia, small for gestational age,
      late fetal death, and congenital malformations, especially neural tube defects.
      OBJECTIVE: The aim was to review the potential complications associated with
      obesity and pregnancy. RESULTS: Obesity is associated with a higher risk of all
      reviewed complications except small for gestational age.

PMID- 15488116
TI  - Nitric oxide as putative second messenger in nerve-induced cervical gland
      secretion in the guinea-pig.
AB  - Uterine cervical secretory cells receive a sympathetic cholinergic secretomotor
      innervation. It has been suggested that glandular nitric oxide (NO) production is
      a prerequisite for muscarinic-induced carbohydrate secretion in the endometrium
      and the seminal vesicle. A similar pattern for nerve-induced carbohydrate
      secretion in the cervix could be assumed. Nitric oxide synthase (NOS) activity
      was evaluated via formation of L-citrulline from L-arginine. The NADPH-diaphorase
      nitroblue technique was used for histochemical investigation. The cervix with the
      adjacent hypogastric nerve was placed in an isolated organ bath and the secretion
      was evaluated as an amount of carbohydrate. A calcium-dependent formation of
      citrulline was found in the cervix indicating NO formation. Strong NADPH-staining
      cells were found in the glandular ducts and in the glandular linings of the
      cervix. Stimulation of the hypogastric nerve induced carbohydrate secretion,
      which was inhibited by N-nitro-L-arginine methyl ester (L-NAME). D-NAME did not
      affect the secretory response. Carbachol and the NO donor glyceryl trinitrate
      (GTN) induced carbohydrate secretion in the cervical glands. No synergistic
      effect was noted probably due to an all-or-none type of secretion. N-nitro-L
      arginine (L-NNA) and L-NAME inhibited carbachol-induced secretion. The results
      suggest that glandular NO production is a prerequisite for the autonomic nervous
      modulation of cervical secretion in the guinea-pig. This could have implications
      regarding fertility and fecundity.

PMID- 15488118
TI  - Correlation between self-reported gestational age and ultrasound measurements.
AB  - BACKGROUND: We studied the agreement between different measurements of
      gestational age, i.e. self-reported gestational age in the Danish National Birth
      Cohort Study, ultrasound-estimated gestational age from the medical records in
      one Danish county and gestational age from the Danish National Hospital Discharge
      Register. METHODS: The ultrasound-estimated gestational length was based on the
      size of the biparietal diameter. The ultrasound-estimated gestational length was
      related to corrected and uncorrected last menstrual period estimates in the
      Danish National Cohort Study, and to the gestational length recorded in the
      Danish National Discharge Register. Non-parametric statistics were used in the
      analysis. RESULTS: The gestational ages estimated by ultrasound were 2-3 days
      shorter than gestational ages estimated by the other methods. The gestational
      ages recorded by the Discharge Register and the gestational ages based on
      corrected last menstrual period did not differ significantly. CONCLUSION: The
      self-reported gestational age in The Danish National Birth Cohort is in good
      concordance both with data from the National Hospital Discharge Register and with
      ultrasound-estimated gestational age.

PMID- 15488117
TI  - Preventive effect of recombinant human lactoferrin on lipopolysaccharide-induced
      preterm delivery in mice.
AB  - BACKGROUND: In order to investigate whether recombinant human lactoferrin (rh-LF)
      has the same effect as bovine LF (b-LF) for the prevention of preterm delivery,
      we conducted the following animal studies. METHODS: Female C3H/HeNCrj mice were
      pair-mated with male Crj:B6D2F1 mice. As a model of preterm delivery, on day 15
      of gestation, a 50 microg/kg intraperitoneal injection of lipopolysaccharide
      (LPS) was administered twice with a 3-hr interval between injections (14:00 and
      17:00 hours). At 1 hr prior to each LPS injection (13:00 and 16:00 hours), an
      intraperitoneal injection of saline, b-LF, or rh-LF (1 mg/body) was administered.
      In non-LPS-treated controls, an intraperitoneal injection of saline was
      administered four times (13:00, 14:00, 16:00, and 17:00 hours). We measured body
      weight and recorded delivery time. To measure plasma levels of interleukin-6 (IL
      6), other pregnant mice, in which the same preparation as mentioned above had
      been done, were killed 6 h after the second LPS injection and blood samples were
      obtained. RESULTS: Delivery occurred in preterm (16.2 +/- 0.4 days of gestation)
      in all LPS-treated mice not administered LF. LF significantly prolonged gestation
      of LPS-treated mice: LPS + b-LF, 17.8 +/- 0.3 days; LPS + rh-LF, 18.2 +/- 1.3
      days (p < 0.05). LF (1 mg/body) significantly suppressed plasma IL-6 in LPS
      treated mice: LPS + b-LF, 1060 +/- 154; LPS + rh-LF, 244.2 +/- 59.4; and LPS
      without LF, 1628 +/- 115 pg/ml (p < 0.05). CONCLUSIONS: rh-LF has an effect of
      prolongation of gestation in LPS-induced preterm delivery in mice, suppressing
      LPS-induced plasma IL-6 augmentation.

PMID- 15488119
TI  - Recurrent preeclampsia and perinatal outcome: a study of women with recurrent
      preeclampsia compared with women with preeclampsia who remained normotensive
      during their prior pregnancies.
AB  - OBJECTIVE: To evaluate the impact of preeclampsia recurrence on perinatal
      outcome. MATERIALS AND METHODS: A case-controlled study was performed in
      multiparous women who developed preeclampsia in index pregnancy (n = 64). Among
      these, women who had preeclampsia in previous pregnancies (n = 21) were compared
      to those who remained normotensive during their prior pregnancies (n = 43).
      Maternal and fetal variables were compared. Multivariate logistic analyses were
      performed to examine the impact of preeclampsia recurrence on fetal loss, preterm
      delivery, small for gestational age (SGA) occurrence and respiratory distress
      syndrome adjusted for confounding variables. RESULTS: No statistical significant
      difference was observed between the two groups in terms of age, delivery weeks,
      steroid use and laboratory markers. Fetal loss was higher in women with recurrent
      preeclampsia (19.0%) than in women with preeclampsia who had a normotensive
      pregnancy history (4.7%), with adjusted odds ratio (OR) of 5.77 [95% confidence
      interval (CI) 0.84-39.54]. CONCLUSION: Women with recurrent preeclampsia had a
      higher rate of perinatal loss compared to women with preeclampsia who were
      normotensive in their prior pregnancies.

PMID- 15488120
TI  - Bone turnover from early pregnancy to postweaning.
AB  - BACKGROUND: To elucidate the sequences of changes in bone metabolism and bone
      density during pregnancy, lactation and postweaning. METHODS: Women were
      recruited (n = 254) in early pregnancy and followed for 2 years. Markers of bone
      formation (osteocalcin) and resorption (NTx) were measured at five occasions.
      Bone mineral density (BMD) of whole-body and lumbar spine L1-L4 (DXA) and
      ultrasonography of os calcis were measured in a subgroup (n = 14). RESULTS: NTx
      appeared bone specific in comparison to pyridinolines. NTx started to increase
      early in pregnancy and remained elevated during lactation (p < 0.001).
      Osteocalcin was low during pregnancy, but peaked during lactation (p < 0.018).
      The subsequent decrease was associated with time since resumption of menses (r2 =
      0.23; p < 0.001). There was indication of a decrease in calcaneal bone mass
      during pregnancy and an evident decrease in lumbar spine (p = 0.041) and os
      calcis (p = 0.037) during lactation. No detectable decrease was identified in
      whole-body BMD (p = 0.090) during lactation, but in general, BMD was higher in
      whole-body (1.9%) and lumbar spine (6.6%) 18 months postpartum than during
      puerperium (p = 0.003). CONCLUSION: According to the bone metabolic markers, bone
      resorption increased early in pregnancy and remained elevated over lactation,
      while bone formation increased during lactation, probably regulated by mechanisms
      associated with absence of menses. The high metabolic bone turnover during late
      pregnancy and lactation lead to a decline in cancellous bone mass during
      lactation, but this seemed beneficial for BMD postweaning.

PMID- 15488121
TI  - The Tyr113His polymorphism in exon 3 of the microsomal epoxide hydrolase gene is
      a risk factor for perinatal mortality.
AB  - BACKGROUND: A genetic predisposition to impaired detoxification of oxidative or
      chemical stress could play a role in the etiology of perinatal mortality. In this
      pilot study we investigated the risk of perinatal mortality in relation to
      genetic polymorphism in microsomal epoxide hydrolase (EPHX) and glutathione S
      transferase P1 (GSTP1) in women who experienced perinatal mortality caused by
      placental pathology, congenital disorders and complications of premature delivery
      and their male partners. METHODS: Genomic DNA of couples (72 females and 46
      males) with a history of perinatal mortality and control couples (71 females and
      66 males) with no complications in their obstetric history were analyzed for the
      presence of the polymorphisms in exon 3 of EPHX (Tyr113His) and GSTP1
      (Ile105Val). RESULTS: A similar distribution of the GSTP1 polymorphism was found
      in all subjects investigated. In women who experienced perinatal mortality, we
      demonstrated a higher prevalence of the EPHX His113/His113 genotype, which could
      result in a lower enzyme activity, compared with controls (25% vs. 9%; chi2 = 5.7
      and p < 0.02), with an odds ratio (95% confidence interval) of 3.5 (1.1-12.7).
      CONCLUSION: Our results suggest that the maternal Tyr113His polymorphism in EPHX
      may be a risk factor for perinatal mortality. However, more research is needed to
      determine the implication of this finding.

PMID- 15488122
TI  - Fetal home monitoring for the prenatal management of gastroschisis.
AB  - BACKGROUND: Fetal distress is a frequent complication of gastroschisis, and could
      be screened for by home monitoring, as many pregnant women expecting an affected
      child live far away from a specialized perinatal center. This study was
      undertaken to audit a policy of fetal home monitoring (FHM) to achieve early
      detection of fetal heart rate (FHR) abnormalities in gastroschisis. METHODS:
      Daily FHM was started at a median age of 30 weeks in 31 pregnant women referred
      following prenatal diagnosis of isolated gastroschisis. Monitoring was considered
      abnormal in cases with decelerations, tachycardia, bradycardia, decreased
      baseline variability or absence of accelerations. When an ominous FHR was
      detected and confirmed by in-hospital monitoring, an emergency cesarean section
      (C-section) was indicated. Otherwise, an elective C-section was planned. RESULTS:
      In 20 cases FHM remained normal. There were 16 elective C-sections, two emergency
      C-sections for FHR abnormalities detected by in-hospital monitoring, and two
      spontaneous premature vaginal deliveries. In 11 cases, an abnormal FHM was
      detected. There was one intrauterine death with acute ischemic necrosis of the
      large bowel. The other abnormalities consisted of decreased baseline variability
      with tachycardia (n = 7) or without tachycardia (n = 3) and were confirmed by in
      hospital follow-up in nine cases, leading to emergency C-section. CONCLUSION: The
      high rate of abnormal FHR patterns picked up by FHM in gastroschisis led to a
      rate of emergency C-sections of 9/31. However, this strategy failed to prevent
      one intrauterine death due to acute bowel necrosis.

PMID- 15488123
TI  - Ultrasonic fetal weight estimation in women with pregnancy complicated by
      diabetes.
AB  - Ultrasound fetal weight estimation is a key element of obstetric management in
      pregnancy complicated by diabetes. Ultrasound estimates based on formulae
      utilizing abdominal circumference measurements only appear more accurate in this
      group of women. However, they are still associated with errors of up to 25% of
      the true birthweight.

PMID- 15488124
TI  - Increased serum levels of neopterin and soluble interleukin-2 receptor in
      intrahepatic cholestasis of pregnancy.
AB  - OBJECTIVES: The etiology of intrahepatic cholestasis of pregnancy (ICP), a
      pregnancy-specific complication, remains not completely understood. Some
      alterations of immunity in ICP were reported, but the profile of immune
      alteration was far from clarified. The aim of this investigation was to
      characterize the changes of serum levels of neopterin, a marker for the
      activation of macrophage, and soluble interleukin-2 receptor (sIL-2R), a marker
      for the activation of lymphocyte, in ICP. METHODS: Serum levels of neopterin and
      sIL-2R were assayed with enzyme linked immunosorbent assay (ELISA) in 30 patients
      with ICP and 30 normal pregnant women. Student's t-test was used for statistic
      analysis, and p < 0.05 was considered significant. RESULTS: Compared with
      control, serum levels of neopterin (p < 0.005) and sIL-2R (p < 0.05) were
      increased significantly in women with ICP. CONCLUSIONS: Activation of monocyte
      macrophage and lymphocyte was demonstrated in ICP, and the participation of the
      activation of macrophage and lymphocyte in pathogenesis of the disease could be
      assumed.

PMID- 15488125
TI  - Neonatal outcome in a Danish national cohort of 8602 children born after in vitro
      fertilization or intracytoplasmic sperm injection: the role of twin pregnancy.
AB  - BACKGROUND: In Denmark, 4% of all infants are born after in vitro fertilization
      (IVF) or intracytoplasmic sperm injection (ICSI) and 40% of these children are
      twins. METHODS: We investigated neonatal outcome in a complete Danish IVF/ICSI
      birth cohort including 8602 infants born between 1995 and 2000: 3438 twins (40%)
      and 5164 singletons (60%). Births conceived after IVF or ICSI were identified by
      record linkage with the Danish IVF Registry and the National Medical Birth
      Registry. Data on neonatal outcome were collected from the National Patient
      Registry. RESULTS: IVF/ICSI twins had a 10-fold increased age- and parity
      adjusted risk of delivery before 37 completed weeks [odds ratio (OR) 9.9, 95%
      confidence interval (95% CI) 8.7-11.3] and a 7.4-fold increased risk of delivery
      before 32 completed weeks (OR 7.4, 95% CI 5.6-9.8) compared with singletons.
      Correspondingly, ORs of birthweight <2500 g and birthweight <1500 g in twins were
      11.8 (95% CI 10.3-13.6) and 5.4 (95% CI 4.1-7.0), respectively. The stillbirth
      rate was doubled in twins (13.1/1000) compared with singletons (6.6/1000) (p =
      0.002). The risk of cesarean section and of admittance to a neonatal intensive
      care unit (NICU) was 4.6- and 1.8-fold higher in IVF/ICSI twins than in
      singletons. The rate of major malformations was 40.4/1000 in twins and 36.8/1000
      in singletons (p = 0.4), whereas the total malformation rate (major + minor) was
      higher in twins (73.7/1000) than in singletons (55.0/1000) (p = 0.001). After
      exclusion of patent ductus arteriosus (PDA), which is strongly associated with
      preterm birth, no significant differences in any malformation rates were observed
      between twins and singletons. Apart from the frequency of ICSI children with
      hypospadias, which reached a significance level of p = 0.05, malformation rates
      in ICSI children were similar to those in IVF children. CONCLUSIONS: This study
      indicates that neonatal outcome in IVF/ICSI twins is considerably poorer than in
      singletons. Thus, the impact is to draw the attention of clinicians to the
      benefit of elective single embryo transfer (eSET).

PMID- 15488126
TI  - Perinatal outcome of twin pregnancies after in vitro fertilization.
AB  - BACKGROUND: There are conflicting data concerning perinatal outcome of twin, in
      vitro fertilization (IVF) pregnancies. The aim of this study was to evaluate and
      compare perinatal and neonatal outcomes in twin IVF pregnancies to those of
      spontaneously conceived twin gestations. METHODS: The medical files of 73 IVF and
      148 naturally conceived twin pregnancies were studied retrospectively. Data
      concerning maternal characteristics, obstetric complications, and neonatal
      outcome were recorded and compared by chi2 test. The one-way analysis of variance
      (anova) was used to compare the means of groups. RESULTS: Mean maternal age, the
      proportion of nulliparous women, and the incidence of premature rupture of
      membranes, cesarean section, and premature delivery were significantly higher in
      the study group. The mean birthweight was significantly lower, the frequency of
      admission to the intensive care unit and the duration of hospitalization were
      significantly higher in the study group. The incidence of intraventricular
      hemorrhage was significantly higher in the IVF group. The number of perinatal
      deaths was similar. CONCLUSION: IVF twin pregnancies are at greater risk for
      obstetric complications and adverse neonatal outcome in comparison with naturally
      conceived twin gestations.

PMID- 15488127
TI  - Ki-67 expression in patients with uterine leiomyomas, uterine smooth muscle
      tumors of uncertain malignant potential (STUMP) and uterine leiomyosarcomas
      (LMS).
AB  - BACKGROUND: The aim of the current study was to evaluate the expression of Ki-67
      in uterine smooth muscle tumors, comparing leiomyomas, uterine smooth muscle
      tumors of uncertain malignant potential (STUMP) and uterine leiomyosarcomas (LMS)
      and to prove the accuracy of a Ki-67 expression as a useful parameter in the
      diagnosis of LMS. METHODS: Ki-67 was assessed using immunohistochemistry from
      paraffin-embedded tissue in 20 patients with uterine LMS, 22 cases of STUMP and
      25 cases of leiomyomas. RESULTS: Ki-67 was present in 10/20 (50%) LMS, in 0/22
      (0%) STUMP and in 2/25 (8%) leiomyomas. Significant differences regarding the
      frequency of Ki-67 expression were observed between LMS and STUMP (p = 0.0001) as
      well as between LMS and leiomyomas (p = 0.002), but not between STUMP and
      leiomyomas (p = 0.491). Likewise, the staining intensity differed significantly
      between LMS and leiomyomas (p = 0.018) as well as between LMS and STUMP (p =
      0.002), but not between STUMP and leiomyomas (p = 0.368). CONCLUSIONS: Our
      results demonstrate that the significantly elevated Ki-67 antigen expression in
      LMS, which correlates well with the rapid growth of these malignant tumors, may
      be a useful immunohistochemical parameter to distinguish between cases of
      malignant smooth muscle tumors and those of uncertain or borderline histology.

PMID- 15488128
TI  - Myxedematous coma in a laboring woman suggested a pre-eclamptic coma: a case
      report.
AB  - Myxedematous coma in pregnancy is a rare incident. We present a case of
      Myxedematous coma in a laboring woman that suggested a pre-eclamptic coma and
      finalized with a healthy baby.

PMID- 15488129
TI  - Huge pedunculated fibroma of the vulva.

PMID- 15488130
TI  - Anogenital lymphangioma circumscriptum masquerading as condyloma accuminata.

PMID- 15488131
TI  - Pedunculated cavernous lymphangioma of the vulva.

PMID- 15488133
TI  - The third-trimester maternal plasma estradiol levels in normotensive pregnant
      women.

PMID- 15488135
TI  - Betamethasone is the drug of choice in threatened preterm labor.

PMID- 15488138
TI  - Verbal autopsy of 80,000 adult deaths in Tamilnadu, South India.
AB  - BACKGROUND: Registration of the fact of death is almost complete in the city of
      Chennai and not so in the rural Villupuram district in Tamilnadu, India. The
      cause of death is often inadequately recorded on the death certificate in
      developing countries like India. A special verbal autopsy (VA) study of 48,000
      adult (aged >or= 25 yrs) deaths in the city of Chennai (urban) during 1995-97 and
      32,000 in rural Villupuram during 1997-98 was conducted to arrive at the probable
      underlying cause of death to estimate cause specific mortality. METHODS: A ten
      day training on writing verbal autopsy (VA) report for adult deaths was given to
      non-medical graduates with at least 15 years of formal education. They
      interviewed surviving spouse/close associates of the deceased to write a verbal
      autopsy report in local language (Tamil) on the complaints, symptoms, signs,
      duration and treatment details of illness prior to death. Each report was
      reviewed centrally by two physicians independently. Random re-interviewing of 5%
      of the VA reports was done to check the reliability and reproducibility of the VA
      report. The validity of VA diagnosis was assessed only for cancer deaths.
      RESULTS: Verbal autopsy reduced the proportion of deaths attributed to
      unspecified and unknown causes from 54% to 23% (p < 0.0001) in urban and from 41%
      to 26% (p < 0.0001) in rural areas in Tamilnadu for adult deaths (>or= 25). The
      sensitivity of VA to identify cancer was 95% in the age group 25-69. CONCLUSION:
      A ten day training programme to write verbal autopsy report with adequate feed
      back sessions and random sampling of 5% of the verbal autopsy reports for re
      interview worked very well in Tamilnadu, to arrive at the probable underlying
      cause of death reliably for deaths in early adult life or middle age (25-69
      years) and less reliably for older ages (70+). Thus VA is practicable for deaths
      in early adult life or middle age and is of more limited value in old age.

PMID- 15488139
TI  - Atherosclerotic renal artery stenosis: one year outcome of total and separate
      kidney function following stenting.
AB  - BACKGROUND: Renal artery stenosis (RAS) is a known cause of hypertension and
      ischemic nephropathy. Stenting of the artery is a valid approach, in spite of
      cases of unexpected adverse evolution of renal function. METHODS: In this study,
      27 patients with unilateral RAS were subjected to stenting and followed for a
      period of one year, while 19 patients were observed while on medical treatment
      only. The group of 27 patients, 67.33 +/- 6.8 years of age, creatinine of 2.15 +/
      0.9 mg/dl, following stenting, were followed at intervals with biochemical
      tests, renal scintigraphy and doppler ultrasonography. The control group (70.0 +/
      6.1 years, creatinine 1.99 +/- 0.7 mg/dl) was also followed for one year.
      RESULT: One year after stenting mean creatinine clearance (Ccr) increased from
      36.07 +/- 17.2 to 40.4 +/- 21.6 ml/min (NS). Arterial BP, decreased after 1,3,6,
      and 12 months (p < 0.05). The number of antihypertensive drugs also decreased (p
      < 0.05). A significant increase in proteinuria was also observed. In the control
      group both Ccr, BP and proteinuria did not show significant changes. Based on
      renal scintigraphy and Ccr at subsequent times, it was possible to evaluate the
      timecourse of renal function in both kidneys of the stented patients. In the
      stented kidneys Ccr increased significantly. On the controlateral kidney a
      decrease of renal function (p < 0.05) was observed. Resistance index appeared to
      be a risk factor of the functional outcome. CONCLUSIONS: Stenting of RAS due to
      atherosclerosis is followed by stabilization or improvement of Ccr, mainly at the
      stented kidney, while contralateral renal function showed a decrease.

PMID- 15488140
TI  - Melanoma-restricted genes.
AB  - Human metastatic cutaneous melanoma has gained a well deserved reputation for its
      immune responsiveness. The reason(s) remain(s) unknown. We attempted previously
      to characterize several variables that may affect the relationship between tumor
      and host immune cells but, taken one at the time, none yielded a convincing
      explanation. With explorative purposes, high-throughput technology was applied
      here to portray transcriptional characteristics unique to metastatic cutaneous
      melanoma that may or may not be relevant to its immunogenic potential. Several
      functional signatures could be identified descriptive of immune or other
      biological functions. In addition, the transcriptional profile of metastatic
      melanoma was compared with that of primary renal cell cancers (RCC) identifying
      several genes co-coordinately expressed by the two tumor types. Since RCC is
      another immune responsive tumor, commonalities between RCC and melanoma may help
      untangle the enigma of their potential immune responsiveness. This purely
      descriptive study provides, therefore, a map for the investigation of metastatic
      melanoma in future clinical trials and at the same time may invite consideration
      of novel therapeutic targets.

PMID- 15488141
TI  - Feeding of soy protein isolate to rats during pregnancy and lactation suppresses
      formation of aberrant crypt foci in their progeny's colons: interaction of diet
      with fetal alcohol exposure.
AB  - Soy protein isolate (SPI) in the diet may inhibit colon tumorigenesis. We
      examined azoxymethane (AOM)-induced aberrant crypt foci (ACF) in male rats in
      relation to lifetime, pre-weaning, or post-weaning dietary exposure to SPI and
      also within the context of fetal alcohol exposure. Pregnant Sprague Dawley rats
      were fed AIN-93G diets containing casein (20%, the control diet) or SPI (20%) as
      the sole protein source starting on gestation day 4 (GD 4). Progeny were weaned
      on postnatal day (PND) 21 to the same diet as their dams and were fed this diet
      until termination of the experiment at PND 138. Rats received AOM on PND 89 and
      96. Lifetime (GD 4 to PND 138) feeding of SPI led to reduced frequency of ACF
      with 4 or more crypts in the distal colon. Progeny of dams fed SPI only during
      pregnancy and lactation or progeny fed SPI only after weaning exhibited similarly
      reduced frequency of large ACF in distal colon. Number of epithelial cells, in
      the distal colon, undergoing apoptosis was unaffected by diet. SPI reduced weight
      gain and adiposity, but these were not correlated with fewer numbers of large
      ACF. Lifetime SPI exposure similarly inhibited development of large ACF in
      Sprague Dawley rats whose dams were exposed to ethanol during pregnancy. In
      summary, feeding of SPI to rat dams during pregnancy and lactation suppresses
      numbers of large ACF in their progeny, implying a long-term or permanent change
      elicited by the maternal diet. Moreover, results support the use of ACF as an
      intermediate endpoint for elucidating effects of SPI and its biochemical
      constituents in colon cancer prevention in rats.

PMID- 15488142
TI  - Fully human IgG and IgM antibodies directed against the carcinoembryonic antigen
      (CEA) Gold 4 epitope and designed for radioimmunotherapy (RIT) of colorectal
      cancers.
AB  - BACKGROUND: Human monoclonal antibodies (MAbs) are needed for colon cancer
      radioimmunotherapy (RIT) to allow for repeated injections. Carcinoembryonic
      antigen (CEA) being the reference antigen for immunotargeting of these tumors, we
      developed human anti-CEA MAbs. METHODS: XenoMouse-G2 animals were immunized with
      CEA. Among all the antibodies produced, two of them, VG-IgG2kappa and VG-IgM,
      were selected for characterization in vitro in comparison with the human-mouse
      chimeric anti-CEA MAb X4 using flow cytometry, surface plasmon resonance, and
      binding to radiolabeled soluble CEA and in vivo in human colon carcinoma LS174T
      bearing nude mice. RESULTS: Flow cytometry analysis demonstrated binding of MAbs
      on CEA-expressing cells without any binding on NCA-expressing human granulocytes.
      In a competitive binding assay using five reference MAbs, directed against the
      five Gold CEA epitopes, VG-IgG2kappa and VG-IgM were shown to be directed against
      the Gold 4 epitope. The affinities of purified VG-IgG2kappa and VG-IgM were
      determined to be 0.19 +/- 0.06 x 10(8) M(-1) and 1.30 +/- 0.06 x 10(8) M(-1),
      respectively, as compared with 0.61 +/- 0.05 x 10(8) M(-1) for the reference MAb
      X4. In a soluble phase assay, the binding capacities of VG-IgG2kappa and VG-IgM
      to soluble CEA were clearly lower than that of the control chimeric MAb X4. A
      human MAb concentration of about 10(-7) M was needed to precipitate
      approximatively 1 ng 125I-rhCEA as compared with 10(-9) M for MAb X4, suggesting
      a preferential binding of the human MAbs to solid phase CEA. In vivo, 24 h post
      injection, 125I-VG-IgG2kappa demonstrated a high tumor uptake (25.4 +/-
      7.3%ID/g), close to that of 131I-X4 (21.7 +/- 7.2%ID/g). At 72 h post-injection,
      125I-VG-IgG2kappa was still concentrated in the tumor (28.4 +/- 11.0%ID/g)
      whereas the tumor concentration of 131I-X4 was significantly reduced (12.5 +/-
      4.8%ID/g). At no time after injection was there any accumulation of the
      radiolabeled MAbs in normal tissues. A pertinent analysis of VG-IgM
      biodistribution was not possible in this mouse model in which IgM displays a very
      short half-life due to poly-Ig receptor expression in the liver. CONCLUSION: Our
      human anti-CEA IgG2kappa is a promising candidate for radioimmunotherapy in
      intact form, as F(ab')2 fragments, or as a bispecific antibody.

PMID- 15488143
TI  - Potentially inappropriate prescriptions for older patients in long-term care.
AB  - BACKGROUND: Inappropriate medication use is a major healthcare issue for the
      elderly population. This study explored the prevalence of potentially
      inappropriate prescriptions (PIPs) in long-term care in metropolitan Quebec.
      METHODS: A cross sectional chart review of 2,633 long-term care older patients of
      the Quebec City area was performed. An explicit criteria list for PIPs was
      developed based on the literature and validated by a modified Delphi method.
      Medication orders were reviewed to describe prescribing patterns and to determine
      the prevalence of PIPs. A multivariate analysis was performed to identify
      predictors of PIPs. RESULTS: Almost all residents (94.0%) were receiving one or
      more prescribed medication; on average patients had 4.8 prescribed medications. A
      majority (54.7%) of treated patients had a potentially inappropriate prescription
      (PIP). Most common PIPs were drug interactions (33.9% of treated patients),
      followed by potentially inappropriate duration (23.6%), potentially inappropriate
      medication (14.7%) and potentially inappropriate dosage (9.6%). PIPs were most
      frequent for medications of the central nervous system (10.8% of prescribed
      medication). The likelihood of PIP increased significantly as the number of drugs
      prescribed increased (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.33
      1.43) and with the length of stay (OR: 1.78, CI: 1.43-2.20). On the other hand,
      the risk of receiving a PIP decreased with age. CONCLUSION: Potentially
      inappropriate prescribing is a serious problem in the highly medicated long-term
      care population in metropolitan Quebec. Use of explicit criteria lists may help
      identify the most critical issues and prioritize interventions to improve quality
      of care and patient safety.

PMID- 15488144
TI  - Physical restraint use among nursing home residents: A comparison of two data
      collection methods.
AB  - BACKGROUND: In view of the issues surrounding physical restraint use, it is
      important to have a method of measurement as valid and reliable as possible. We
      determined the sensitivity and specificity of physical restraint use a) reported
      by nursing staff and b) reviewed from medical and nursing records in nursing home
      settings, by comparing these methods with direct observation. METHODS: We sampled
      eight care units in skilled nursing homes, seven care units in nursing homes and
      one long-term care unit in a hospital, from eight facilities which included 28
      nurses and 377 residents. Physical restraint use was assessed the day following
      three periods of direct observation by two different means: interview with one or
      several members of the regular nursing staff, and review of medical and nursing
      records. Sensitivity and specificity values were calculated according to 2-by-2
      contingency tables. Differences between the methods were assessed using the phi
      coefficient. Other information collected included: demographic characteristics,
      disruptive behaviors, body alignment problems, cognitive and functional skills.
      RESULTS: Compared to direct observation (gold standard), reported restraint use
      by nursing staff yielded a sensitivity of 87.4% at a specificity of 93.7% (phi =
      0.84). When data was reviewed from subjects' medical and nursing records,
      sensitivity was reduced to 74.8%, and specificity to 86.3% (phi = 0.54).
      Justifications for restraint use including risk for falls, agitation, body
      alignment problems and aggressiveness were associated with the use of physical
      restraints. CONCLUSIONS: The interview of nursing staff and the review of medical
      and nursing records are both valid and reliable techniques for measuring physical
      restraint use among nursing home residents. Higher sensitivity and specificity
      values were achieved when nursing staff was interviewed as compared to reviewing
      medical records. This study suggests that the interview of nursing staff is a
      more reliable method of data collection.

PMID- 15488145
TI  - Enhancing the African bioethics initiative.
AB  - BACKGROUND: Medical ethics has existed since the time of Hippocrates. However,
      formal training in bioethics did not become established until a few decades ago.
      Bioethics has gained a strong foothold in health sciences in the developed world,
      especially in Europe and North America. The situation is quite different in many
      developing countries. In most African countries, bioethics - as established and
      practiced today in the west- is either non-existent or is rudimentary.
      DISCUSSION: Though bioethics has come of age in the developed and some developing
      countries, it is still largely "foreign" to most African countries. In some parts
      of Africa, some bioethics conferences have been held in the past decade to create
      research ethics awareness and ensure conformity to international guidelines for
      research with human participants. This idea has arisen in recognition of the
      genuine need to develop capacity for reviewing the ethics of research in Africa.
      It is also a condition required by external sponsors of collaborative research in
      Africa. The awareness and interest that these conferences have aroused need to be
      further strengthened and extended beyond research ethics to clinical practice. By
      and large, bioethics education in schools that train doctors and other health
      care providers is the hook that anchors both research ethics and clinical ethics.
      SUMMARY: This communication reviews the current situation of bioethics in Africa
      as it applies to research ethics workshops and proposes that in spite of the
      present efforts to integrate ethics into biomedical research in Africa, much
      still needs to be done to accomplish this. A more comprehensive approach to
      bioethics with an all-inclusive benefit is to incorporate formal ethics education
      into health training institutions in Africa.

PMID- 15488146
TI  - Social Phobia in an Italian region: do Italian studies show lower frequencies
      than community surveys conducted in other European countries?
AB  - BACKGROUND: The lifetime prevalence of Social Phobia (SP) in European countries
      other than Italy has been estimated to range from 3.5% to 16.0%. The aim of this
      study was to assess the frequency of SP in Sardinia (Italy) in order to verify
      the evidence of a lower frequency of SP in Italy observed in previous studies
      (from 1.0% to 3.1%). METHODS: A randomised cross sample of 1040 subjects, living
      in Cagliari, in rural areas, and in a mining district in Sardinia were
      interviewed using a Simplified version of the Composite International Diagnostic
      Interview (CIDIS). Diagnoses were made according to the 10th International
      Classification of Diseases (ICD-10). RESULTS: Lifetime prevalence of SP was 2.2%
      (males: 1.5%, females: 2.8%) whereas 6-month prevalence resulted in 1.5% (males:
      0.9%, females: 2.1%). Mean age at onset was 16.2 +/- 9.3 years. A statistically
      significant association was found with Depressive Episode, Dysthymia and
      Generalized Anxiety Disorder. CONCLUSIONS: The study is consistent with findings
      reported in several previous studies of a lower prevalence of SP in Italy.
      Furthermore, the results confirm the fact that SP, due to its early onset, might
      constitute an ideal target for early treatment aimed at preventing both the
      accumulation of social disabilities and impairments caused by anxiety and
      avoidance behaviour, as well as the onset of more serious, associated
      complications in later stages of the illness.

PMID- 15488147
TI  - PCOGR: phylogenetic COG ranking as an online tool to judge the specificity of
      COGs with respect to freely definable groups of organisms.
AB  - BACKGROUND: The rapidly increasing number of completely sequenced genomes led to
      the establishment of the COG-database which, based on sequence homologies,
      assigns similar proteins from different organisms to clusters of orthologous
      groups (COGs). There are several bioinformatic studies that made use of this
      database to determine (hyper)thermophile-specific proteins by searching for COGs
      containing (almost) exclusively proteins from (hyper)thermophilic genomes.
      However, public software to perform individually definable group-specific
      searches is not available. RESULTS: The tool described here exactly fills this
      gap. The software is accessible at http://www.uni-wh.de/pcogr and is linked to
      the COG-database. The user can freely define two groups of organisms by selecting
      for each of the (current) 66 organisms to belong either to groupA, to the
      reference groupB or to be ignored by the algorithm. Then, for all COGs a
      specificity index is calculated with respect to the specificity to groupA, i. e.
      high scoring COGs contain proteins from the most of groupA organisms while
      proteins from the most organisms assigned to groupB are absent. In addition to
      ranking all COGs according to the user defined specificity criteria, a graphical
      visualization shows the distribution of all COGs by displaying their abundance as
      a function of their specificity indexes. CONCLUSIONS: This software allows
      detecting COGs specific to a predefined group of organisms. All COGs are ranked
      in the order of their specificity and a graphical visualization allows
      recognizing (i) the presence and abundance of such COGs and (ii) the phylogenetic
      relationship between groupA- and groupB-organisms. The software also allows
      detecting putative protein-protein interactions, novel enzymes involved in only
      partially known biochemical pathways, and alternate enzymes originated by
      convergent evolution.

PMID- 15488149
TI  - Caryoscope: an Open Source Java application for viewing microarray data in a
      genomic context.
AB  - BACKGROUND: Microarray-based comparative genome hybridization experiments
      generate data that can be mapped onto the genome. These data are interpreted more
      easily when represented graphically in a genomic context. RESULTS: We have
      developed Caryoscope, which is an open source Java application for visualizing
      microarray data from array comparative genome hybridization experiments in a
      genomic context. Caryoscope can read General Feature Format files (GFF files), as
      well as comma- and tab-delimited files, that define the genomic positions of the
      microarray reporters for which data are obtained. The microarray data can be
      browsed using an interactive, zoomable interface, which helps users identify
      regions of chromosomal deletion or amplification. The graphical representation of
      the data can be exported in a number of graphic formats, including publication
      quality formats such as PostScript. CONCLUSION: Caryoscope is a useful tool that
      can aid in the visualization, exploration and interpretation of microarray data
      in a genomic context.

PMID- 15488148
TI  - Two Drosophila suppressors of cytokine signaling (SOCS) differentially regulate
      JAK and EGFR pathway activities.
AB  - BACKGROUND: The Janus kinase (JAK) cascade is an essential and well-conserved
      pathway required to transduce signals for a variety of ligands in both
      vertebrates and invertebrates. While activation of the pathway is essential to
      many processes, mutations from mammals and Drosophila demonstrate that regulation
      is also critical. The SOCS (Suppressor Of Cytokine Signaling) proteins in mammals
      are regulators of the JAK pathway that participate in a negative feedback loop,
      as they are transcriptionally activated by JAK signaling. Examination of one
      Drosophila SOCS homologue, Socs36E, demonstrated that its expression is
      responsive to JAK pathway activity and it is capable of downregulating JAK
      signaling, similar to the well characterized mammalian SOCS. RESULTS: Based on
      sequence analysis of the Drosophila genome, there are three identifiable SOCS
      homologues in flies. All three are most similar to mammalian SOCS that have not
      been extensively characterized: Socs36E is most similar to mammalian SOCS5, while
      Socs44A and Socs16D are most similar to mammalian SOCS6 and 7. Although Socs44A
      is capable of repressing JAK activity in some tissues, its expression is not
      regulated by the pathway. Furthermore, Socs44A can enhance the activity of the
      EGFR/MAPK signaling cascade, in contrast to Socs36E. CONCLUSIONS: Two Drosophila
      SOCS proteins have some overlapping and some distinct capabilities. While Socs36E
      behaves similarly to the canonical vertebrate SOCS, Socs44A is not part of a JAK
      pathway negative feedback loop. Nonetheless, both SOCS regulate JAK and EGFR
      signaling pathways, albeit differently. The non-canonical properties of Socs44A
      may be representative of the class of less characterized vertebrate SOCS with
      which it shares greatest similarity.

PMID- 15488150
TI  - Use of and attitudes to a hospital information system by medical secretaries,
      nurses and physicians deprived of the paper-based medical record: a case report.
AB  - BACKGROUND: Most hospitals keep and update their paper-based medical records
      after introducing an electronic medical record or a hospital information system
      (HIS). This case report describes a HIS in a hospital where the paper-based
      medical records are scanned and eliminated. To evaluate the HIS comprehensively,
      the perspectives of medical secretaries and nurses are described as well as that
      of physicians. METHODS: We have used questionnaires and interviews to assess and
      compare frequency of use of the HIS for essential tasks, task performance and
      user satisfaction among medical secretaries, nurses and physicians. RESULTS: The
      medical secretaries use the HIS much more than the nurses and the physicians, and
      they consider that the electronic HIS greatly has simplified their work. The work
      of nurses and physicians has also become simplified, but they find less
      satisfaction with the system, particularly with the use of scanned document
      images. CONCLUSIONS: Although the basis for reference is limited, the results
      support the assertion that replacing the paper-based medical record primarily
      benefits the medical secretaries, and to a lesser degree the nurses and the
      physicians. The varying results in the different employee groups emphasize the
      need for a multidisciplinary approach when evaluating a HIS.

PMID- 15488151
TI  - Autoimmune inflammatory disorders, systemic corticosteroids and pneumocystis
      pneumonia: a strategy for prevention.
AB  - BACKGROUND: Pneumocystis pneumonia (PCP) is an increasing problem amongst
      patients on immunosuppression with autoimmune inflammatory disorders (AID). The
      disease presents acutely and its diagnosis requires bronchoalveolar lavage in
      most cases. Despite treatment with intravenous antibiotics, PCP carries a worse
      prognosis in AID patients than HIV positive patients. The overall incidence of
      PCP in patients with AID remains low, although patients with Wegener's
      granulomatosis are at particular risk. DISCUSSION: In adults with AID, the risk
      of PCP is related to treatment with systemic steroid, ill-defined individual
      variation in steroid sensitivity and CD4+ lymphocyte count. Rather than opting
      for PCP prophylaxis on the basis of disease or treatment with cyclophosphamide,
      we argue the case for carrying out CD4+ lymphocyte counts on selected patients as
      a means of identifying individuals who are most likely to benefit from PCP
      prophylaxis. SUMMARY: Corticosteroids, lymphopenia and a low CD4+ count in
      particular, have been identified as risk factors for the development of PCP in
      adults with AID. Trimethoprim-sulfamethoxazole (co-trimoxazole) is an effective
      prophylactic agent, but indications for its use remain ill-defined. Further
      prospective trials are required to validate our proposed prevention strategy.

PMID- 15488152
TI  - Student evaluation of an OSCE in paediatrics at the University of the West
      Indies, Jamaica.
AB  - BACKGROUND: The Faculty of Medical Sciences, University of the West Indies first
      implemented the Objective Structured Clinical Examination (OSCE) in the final MB
      Examination in Medicine and Therapeutics during the 2000-2001 academic year.
      Simultaneously, the Child Health Department initiated faculty and student
      training, and instituted the OSCE as an assessment instrument during the Child
      Health (Paediatric) clerkship in year 5. The study set out to explore student
      acceptance of the OSCE as part of an evaluation of the Child Health clerkship.
      METHODS: A self-administered questionnaire was completed by successive groups of
      students immediately after the OSCE at the end of each clerkship rotation. Main
      outcome measures were student perception of examination attributes, which
      included the quality of instructions and organisation, the quality of
      performance, authenticity and transparency of the process, and usefulness of the
      OSCE as an assessment instrument compared to other formats. RESULTS: There was
      overwhelming acceptance of the OSCE in Child Health with respect to the
      comprehensiveness (90%), transparency (87%), fairness (70%) and authenticity of
      the required tasks (58-78%). However, students felt that it was a strong anxiety
      producing experience. And concerns were expressed regarding the ambiguity of some
      questions and inadequacy of time for expected tasks. CONCLUSION: Student feedback
      was invaluable in influencing faculty teaching, curriculum direction and
      appreciation of student opinion. Further psychometric evaluation will strengthen
      the development of the OSCE.

PMID- 15488153
TI  - Transmembrane carbonic anhydrase isozymes IX and XII in the female mouse
      reproductive organs.
AB  - BACKGROUND: Carbonic anhydrase (CA) classically catalyses the reversible
      hydration of dissolved CO2 to form bicarbonate ions and protons. The twelve
      active CA isozymes are thought to regulate a variety of cellular functions
      including several processes in the reproductive systems. METHODS: The present
      study was designed to investigate the expression of transmembrane CAs, CA IX and
      XII, in the mouse uterus, ovary and placenta. The expression of CA IX and XII was
      examined by immunoperoxidase staining method and western blotting. CA II and XIII
      served as positive controls since they are known to be present in the mouse
      reproductive tract. RESULTS: The data of our study indicated that CA XII is
      expressed in the mouse endometrium. Only very faint signal was observed in the
      corpus luteum of the ovary and the placenta remained mainly negative. CA IX
      showed weak reaction in the endometrial epithelium, while it was completely
      absent in the ovary and placenta. CONCLUSION: The conservation of CA XII
      expression in both mouse and human endometrium suggests a role for this isozyme
      in reproductive physiology.

PMID- 15488154
TI  - Reconstruction of putative DNA virus from endogenous rice tungro bacilliform
      virus-like sequences in the rice genome: implications for integration and
      evolution.
AB  - BACKGROUND: Plant genomes contain various kinds of repetitive sequences such as
      transposable elements, microsatellites, tandem repeats and virus-like sequences.
      Most of them, with the exception of virus-like sequences, do not allow us to
      trace their origins nor to follow the process of their integration into the host
      genome. Recent discoveries of virus-like sequences in plant genomes led us to set
      the objective of elucidating the origin of the repetitive sequences. Endogenous
      rice tungro bacilliform virus (RTBV)-like sequences (ERTBVs) have been found
      throughout the rice genome. Here, we reconstructed putative virus structures from
      RTBV-like sequences in the rice genome and characterized to understand
      evolutionary implication, integration manner and involvements of endogenous virus
      segments in the corresponding disease response. RESULTS: We have collected ERTBVs
      from the rice genomes. They contain rearranged structures and no intact ORFs. The
      identified ERTBV segments were shown to be phylogenetically divided into three
      clusters. For each phylogenetic cluster, we were able to make a consensus
      alignment for a circular virus-like structure carrying two complete ORFs.
      Comparisons of DNA and amino acid sequences suggested the closely relationship
      between ERTBV and RTBV. The Oryza AA-genome species vary in the ERTBV copy
      number. The species carrying low-copy-number of ERTBV segments have been reported
      to be extremely susceptible to RTBV. The DNA methylation state of the ERTBV
      sequences was correlated with their copy number in the genome. CONCLUSIONS: These
      ERTBV segments are unlikely to have functional potential as a virus. However,
      these sequences facilitate to establish putative virus that provided information
      underlying virus integration and evolutionary relationship with existing virus.
      Comparison of ERTBV among the Oryza AA-genome species allowed us to speculate a
      possible role of endogenous virus segments against its related disease.

PMID- 15488158
TI  - [Master of science level nursing course. Remarks on the opening talk].

PMID- 15488155
TI  - Production of hemo- and immunoregulatory cytokines by erythroblast antigen+ and
      glycophorin A+ cells from human bone marrow.
AB  - BACKGROUND: Erythroid nuclear cells (ENC) of the bone marrow (BM) have not
      previously been considered as important producers of wide spectrum of haemo- and
      immunoregulatory cytokines. The aim of the current work was to confirm the
      production of the main hemo- and immunoregulatory cytokines in human ENC from BM.
      RESULTS: We used native human BM ENC in our experiments. We for the first time
      have shown, that the unstimulated erythroblasts (Gl A+ or AG-EB+) produced a wide
      spectrum of immunoregulatory cytokines. Human BM ENC produce cytokines such as
      interleukin (IL)-1beta, IL-2, IL-4, IL-6, interferon (IFN)-gamma, transforming
      growth factor (TGF)-beta1, tumor necrosis factor (TNF)-alpha and IL-10. They can
      be sub-divided into glycophorin A positive (Gl A+) and erythroblast antigen
      positive (AG-EB+) cells. To study potential differences in cytokine expression
      between these subsets, ENC were isolated and purified using specific antibodies
      to Gl A and AG-EB and the separated cells were cultivated for 24 hours. The
      cytokine contents of the supernatant were measured by electrochemiluminescence
      immunoassay. Quantitative differences in TGF-beta1 and TNF-alpha production were
      found between Gl A+ and AG-EB+ BM ENC. Furthermore, in vitro addition of
      erythropoietin (EPO) reduced IFN-gamma and IL-2 production specifically by the AG
      EB+ ENC. Thus, Gl A+ and AG-EB+ ENC produce IL-1beta, IL-2, IL-4, IL-6, IFN
      gamma, TGF-beta1 and TNF-alpha. Gl A+ ENC also produce IL-10. CONCLUSION:
      Cytokine production by erythroid nuclear cells suggests that these cells might be
      involved in regulating the proliferation and differentiation of hematopoietic and
      immunocompetent cells in human BM.

PMID- 15488156
TI  - Lithium neuroprotection: molecular mechanisms and clinical implications.
AB  - Lithium has emerged as a neuroprotective agent efficacious in preventing
      apoptosis-dependent cellular death. Lithium neuroprotection is provided through
      multiple, intersecting mechanisms, although how lithium interacts with these
      mechanisms is still under investigation. Lithium increases cell survival by
      inducing brain-derived neurotrophic factor and thereby stimulating activity in
      anti-apoptotic pathways, including the phosphatidylinositol 3-kinase/Akt and the
      mitogen-activated protein kinase pathways. In addition, lithium reduces pro
      apoptotic function by directly and indirectly inhibiting glycogen synthase kinase
      3beta activity and indirectly inhibiting N-methyl-D-aspartate (NMDA)-receptor
      mediated calcium influx. Lithium-induced regulation of anti- and pro-apoptotic
      pathways alters a wide variety of downstream effectors, including beta-catenin,
      heat shock factor 1, activator protein 1, cAMP-response-element-binding protein,
      and the Bcl-2 protein family. Lithium neuroprotection has a wide variety of
      clinical implications. Beyond its present use in bipolar mood disorder, lithium's
      neuroprotective abilities imply that it could be used to treat or prevent brain
      damage following traumatic injury, such as stroke, and neurodegenerative diseases
      such as Huntington's and Alzheimer's diseases.

PMID- 15488159
TI  - [To be with the family during the grieving period].
AB  - This article will present the grieving period from the professionals point of
      view because professionals are with the family from the time of illness is
      discovered until the patient death. The empathy relationship, to be and support
      the family, to contain the tears and the sorrow, to listen the stories and
      memories going through the illness path, are important moments that professionals
      are asked to share with the family and its components after its member death.

PMID- 15488160
TI  - [Pain in newborns and children].
AB  - Pain is a mechanism of defense in response to damaged tissue in order to
      determine a response to remove the cause of damage. Attention to pain control is
      considered a quality index in the pediatric care newborn infants react to pain
      with changes in cardiac and respiratory rate, blood pressure, blood gas, grimace,
      palm sweating, crying, sleep/awake rythm. Measuring pain in child is based on:
      history of the child, changes in behaviour adn vital parameters. Being able to
      explain pain depends on cognitive and language ability of the child. The role of
      the nurse who attend the newborn infant in the neonatal intensive care unit is to
      help baby to cope with acute pain by means of simple manoeuvres like wrapping,
      non nutritive suction, massage, tactile stimulation.

PMID- 15488161
TI  - [Development and validation of a dependence scale].
AB  - Two dimensions are identifiable in nursing hospital caring: a) nurse activities
      based on nurse critical evaluation, carried-out in order to achieve patients
      highest independence; b) nurses activities implementing routinely care and
      medical prescriptions. Therefore, in order to improve the appropriateness of
      their evaluations, nurses should measure patients level of dependence using valid
      and reliable instruments. The study was designed to develop and test a dependency
      scale for hospitalized patients, in order to better identify their needs of
      nursing care; the study was carried out at Udine University Hospital. The
      instrument developed (ADI 8) is a eight-ranks scale. A comparative validation
      between ADI 8, Barthel Index ans Swiss Grid (MS) proved that ADI 8 has more
      discriminative power for medium dependency level subjects. Moreover, ADI 8 showed
      less tendency to overestimate than Bartel Index. Reliability test was carried out
      using paired observers in blind mode. Kendall statistics proved that ADI 8
      possess high reliability for each factor and overall (.80).

PMID- 15488162
TI  - [A randomized study to manage the peripheral intravenous catheter with saline
      washing].
AB  - The scope of this study is to compare the washing of the CVP using normal saline
      solution before each closure and every 6 hours, with closing the CVP using an
      obturator after the suspension of the infused therapy, in function of the
      maintenance of the perviousness and the appearance of complications. The study
      population included 83 patients; using the randomised trail technique, 40
      patients had been assigned to the group of washing and 43 to the group of the
      obturator. The results of this study demonstrate that, in order to maintain the
      perviousness of the CVP and the reduction of the appearance of complications,
      there is no significant difference between the washing of the CVP with normal
      saline solution before each closure with a stopper and every 6 hours, and the
      closure of the CVP with an obturator without washing at the suspension of the
      infused therapy.

PMID- 15488163
TI  - [A survey on working satisfaction of nurses].
AB  - A descriptive survey was performed in the home care service of Azienda ULSS 16 of
      Padova at a sample of nurses. The aim of this study was to identify working
      experience aspects which represent satisfaction or dissatisfaction factors. A
      questionnaire was administered to the 63 nurses of the service, in the same day.
      53 nurses (84%) declare themselves satisfied or very satisfied for the way their
      job stimulates the development of new capabilities, the same for freedom of
      choice the way of working, while 43 (68%) are satisfied or very satisfied for
      profession in general. 55 (87%) state to be unsatisfied or not much satisfied for
      the relation between wages and responsibility, and 42 (67%) for career
      opportunity. Working satisfaction is mainly caused by the quality of the relation
      with patient and his family for 45 nurses (71%); this aspect also prevails
      satisfaction linked to the opportunity of working in autonomy (29, 46%).

PMID- 15488164
TI  - Involving South Asian patients in clinical trials.
AB  - OBJECTIVES: To investigate how South Asian patients conceptualise the notion of
      clinical trials and to identify key processes that impact on trial participation
      and the extent to which communication difficulties, perceptions of risk and
      attitudes to authority influence these decisions. Also to identify whether 'South
      Asian' patients are homogeneous in these issues, and which factors differ between
      different South Asian subgroups and finally how professionals regard the
      involvement of South Asian patients and their views on strategies to increase
      participation. DATA SOURCES: A review of the literature on minority ethnic
      participation in clinical trials was followed by three qualitative interview
      studies. Interviews were taped and transcribed (and translated if required) and
      subjected to framework analysis. Face-to-face interviews were conducted with 25
      health professionals; 60 South Asian lay people who had not taken part in a trial
      and 15 South Asian trial participants. RESULTS: Motivations for trial
      participation were identified as follows: to help society, to improve own health
      or that of family and friends, out of obligation to the doctor and to increase
      scientific knowledge. Deterrents were concerns about drug side-effects, busy
      lifestyles, language, previous bad experiences, mistrust and feelings of not
      belonging to British society. There was no evidence of antipathy amongst South
      Asians to the concept of clinical trials and, overall, the younger respondents
      were more knowledgeable than the older ones. Problems are more likely to be
      associated with service delivery. Lack of being approached was a common response.
      Lay-reported factors that might affect South Asian participation in clinical
      trials include age, language, social class, feeling of not belonging/mistrust,
      culture and religion. Awareness of clinical trials varied between each group.
      There are more similarities than differences in attitudes towards clinical trial
      participation between the South Asian and the general population. Important
      decisions, such as participation in clinical trials, are likely to be made by
      those family members who are fluent in English and younger. Social class appears
      to be more important than ethnicity, and older South Asian people and those from
      working class backgrounds appear to be more mistrustful. Approachable patients
      (of the same gender, social class and fluent in English) tend to be 'cherry
      picked' to clinical trials. This practice was justified because of a lack of time
      and resources and inadequate support. South Asian patients might be
      systematically excluded from trials owing to the increased cost and time
      associated with their inclusion, particularly in relation to the language
      barrier. Under-representation might also be due to passive exclusion associated
      with cultural stereotypes. Other characteristics such as gender, age, educational
      level and social class can also affect trial inclusion. CONCLUSIONS: Effective
      strategies for South Asian recruitment to clinical trials include: using multi
      recruitment strategies; defining the demographic and social profiles of the
      population to be included; using focus groups to identify any potential barriers;
      consulting representative community members to provide assistance in the study;
      ensuring eligibility criteria are set as wide as possible; developing educational
      and recruitment approaches to attract ethnic minority health professionals;
      ensuring health professionals are adequately trained in culturally and ethnically
      orientated service provision; determining the most effective mass media to use in
      study promotion and recruitment; and targeting inner-city, single-handed
      practices likely to have high ethnic minority populations. Future research should
      consider: responses when invited to participate; the role of methodological and
      organisational barriers to recruitment; the complexities of recruitment from a
      health professional perspective; developing culturally sensitive research
      methods; the magnitude of the problem of under-recruitment; strategies to
      encourage inner-city, single-handed GP participation; and other factors affecting
      trial inclusion, such as age, gender, educational level and socio-cultural
      background.

PMID- 15488165
TI  - Clinical and cost-effectiveness of continuous subcutaneous insulin infusion for
      diabetes.
AB  - OBJECTIVES: To assess the clinical and cost-effectiveness of continuous
      subcutaneous insulin infusion (CSII) compared with multiple daily injections
      (MDI) in the delivery of intensive insulin therapy for the treatment of diabetes
      mellitus. DATA SOURCES: Electronic databases, references of retrieved articles
      and manufacturer submissions. Experts in the field were consulted. REVIEW
      METHODS: For the systematic review of clinical and cost-effectiveness, studies
      were assessed for inclusion according to predefined criteria by two reviewers.
      Data extraction and quality assessment were undertaken by one reviewer and
      checked by a second reviewer. Data on clinical effectiveness were synthesised
      through a narrative review with full tabulation of all eligible studies, with
      meta-analysis performed where appropriate. RESULTS: Twenty studies comparing CSII
      with MDI were identified. Quality was generally poor. In adults with Type 1
      diabetes, glycated haemoglobin improved by 0.61% (95% CI -1.29 to 0.07) in longer
      term studies, although this improvement was smaller when a study using bovine
      ultralente was excluded. A reduction in insulin dose with CSII of about 12 units
      per day (-11.90, 95% CI -18.16 to 5.63) was found in short-term studies, with
      smaller differences in longer term studies. Body weight and cholesterol levels
      were similar between treatments. Hypoglycaemic events did not differ
      significantly between CSII and MDI in most trials, but some found fewer events
      with CSII and one found more hypoglycaemia and hypoglycaemic coma with CSII.
      There was no consistency between the studies in patient preference, but progress
      has been made both with insulin pumps and injector pens since the publication of
      many of the older studies. No difference in glycated haemoglobin between CSII and
      MDI was found in pregnancy; one study found less insulin was required by patients
      with CSII, but two other studies found no significant difference. One study of
      adolescents found lower glycated haemoglobin and insulin dose with CSII whereas a
      second study found no significant difference. In CSII analogue insulin was
      associated with lower glycated haemoglobin levels than soluble insulin. No
      economic evaluations comparing CSII with MDI were identified. The estimated
      additional cost of CSII compared to MDI varies from GBP1091 per annum to GBP1680
      per annum, according to the make of the insulin pump and the estimated life of
      the device. These estimates include the costs for the insulin pump, the
      consumables associated with delivery of CSII, and an allowance for the initial
      education required when patients switch from MDI to CSII. The largest component
      of the annual cost for CSII is the cost of consumable items (e.g. infusion sets).
      CONCLUSIONS: When compared with optimised MDI, CSII results in a modest but
      worthwhile improvement in glycated haemoglobin in adults with Type 1 diabetes. It
      has not been possible to establish the longer term benefits of such a difference
      in glycated haemoglobin, although there is an expectation that it would be
      reflected in a reduction in long-term complications. More immediate primary
      benefits from CSII may be associated with an impact on the incidence of
      hypoglycaemic events and the dawn phenomenon, and greater flexibility of
      lifestyle. However, there is limited evidence on this, and information presented
      to offer context on quality-of-life is based on testimonies from those patients
      who have had a positive experience of CSII. The estimated cost to the NHS per
      year for CSII would be around GBP3.5 million in England and Wales if 1% of people
      with Type 1 diabetes used CSII, GBP10.5 million for 3%, and GBP17.5 million for
      5%. Further research should focus on wider benefits of CSII, such as flexibility
      of lifestyle and quality of life, and on the psychological impact of wearing a
      device for 24 hours every day. Research into the use of CSII in children of
      different ages is also needed.

PMID- 15488167
TI  - Evaluating chick Galpha-interacting protein selectivity.
AB  - Regulators of G-protein signaling (RGS) proteins constitute a large family of
      GTPase-accelerating proteins (GAPs) for heterotrimeric G proteins. More than 30
      RGS genes have been identified in mammals. One of these, the Galpha-interacting
      protein (GAIP), interacts preferentially with members of the G(i/o) subfamily of
      G-protein alpha subunits in mammalian cells. A unique isoform of GAIP, derived
      from embryonic chicken dorsal root ganglion neurons, has a short N terminus that
      is only 41% identical to known mammalian orthologs. Consistent with this unique
      primary structure, chick GAIP has higher target specificity than its mammalian
      counterparts. This article describes both in vitro and in vivo methods used to
      characterize chick GAIP selectivity.

PMID- 15488168
TI  - Analyses of Galpha-interacting protein and activator of G-protein-signaling-3
      functions in macroautophagy.
AB  - Macroautophagy or autophagy is an ubiquitous and conserved degradative pathway of
      cytosolic components, macromolecules or organelles, into the lysosome. By using
      biochemical and microscopic methods, which allow one to measure the rate of
      autophagy, the role of two regulators of Gi3 protein activity, activator of G
      protein-signaling-3 (AGS3) and Galpha-interacting protein (GAIP), was studied in
      the control of autophagy in human colon cancer HT-29 cells. In HT-29 cells,
      autophagy is under the control of the Gi3 protein and, when bound to the GTP, the
      Galphai3 protein inhibits autophagy, whereas it stimulates autophagy when bound
      to the GDP. GAIP, which enhances the intrinsic GTPase-activating protein activity
      of the Galphai3 protein, stimulates autophagy by favoring the GDP-bound form of
      Galphai3. We showed that GAIP is phosphorylated on its serine 151 and that this
      phosphorylation is dependent on the presence of amino acids that modulate Raf-1
      activity, the kinase upstream of Erk1/2. AGS3, a guanine nucleotide dissociation
      inhibitor, stimulates autophagy by binding Galphai3 proteins. The intracellular
      localization of AGS3 (Golgi apparatus and endoplasmic reticulum, two membranes
      known to be at the origin of autophagosomes) is consistent with its role in
      autophagy.

PMID- 15488169
TI  - Analysis of RGSZ1 protein interaction with Galphai subunits.
AB  - RGSZ1 has been reported to interact with G-protein subunits of the Galphai family
      and function as a GTPase-accelerating protein on intrinsic Galphai GTPase
      activity. This article describes several experimental approaches and assays used
      to investigate the effect of RGSZ1 on Galphai subunits. The formats described
      here include physical and functional interaction assays by which the association
      of RGSZ1 with Galphai is explored both in vitro and in vivo. The methods
      analyzing physical interaction include pull-down and coimmunoprecipitation
      assays. We also apply yeast two-hybrid techniques to detect RGSZ1 protein
      interaction with Galpha subunits. Additionally, we developed several functional
      assay systems to identify the functional relationship between RGSZ1 and Galphai,
      such as the single turnover GTPase assay, yeast pheromone response assay, mitogen
      activated protein kinase assay, and serum response element reporter assay.

PMID- 15488170
TI  - Analysis of the regulation of microtubule dynamics by interaction of RGSZ1
      (RGS20) with the neuronal stathmin, SCG10.
AB  - Regulators of G protein signaling (RGS proteins) are a diverse family of proteins
      that act to negatively regulate signaling by heterotrimeric G proteins; however,
      recent data have implied additional functions for RGS proteins. Previously, we
      employed the yeast two-hybrid system and identified the microtubule-destabilizing
      protein, superior cervical ganglia neural-specific 10 protein (SCG10), as a
      potential effector protein of RGSZ1. This article describes the expression and
      biochemical purification of both RGSZ1 and SCG10 and details the development of
      various in vitro assays to evaluate microtubule polymerization?depolymerization.
      Both turbidimetric and microscopy-based assays can be employed to study the
      impact that RGS proteins have on SCG10 function. The application of these in
      vitro assays may help identify a novel role for RGS proteins in regulating the
      cytoskeletal network.

PMID- 15488171
TI  - RGS2-mediated regulation of Gqalpha.
AB  - Regulators of G-protein signaling (RGS) proteins are GTPase-activating proteins
      (GAPs) that attenuate signaling by heterotrimeric G proteins. In RGS2, three
      unique residues within the G-protein-binding (RGS) domain have been shown to
      direct its selective inhibition of Gqalpha function. The function of RGS2 as a
      regulator of Gq is also dependent on regulatory sequences in its amino-terminal
      domain that direct its localization to the plasma membrane. This work details
      various approaches that have been used to characterize the relative contribution
      of the RGS and regulatory domains in RGS2 to its function as a regulator of Gq
      signaling. Specifically, assays describing (i) the identification of alpha
      subunit binding partners for RGS2 (ii) the characterization of RGS2-mediated
      inhibition of Gq-dependent phosphatidylinositol signaling in tissue culture
      models, and (iii) the measurement of Gq-dependent calcium responses in vascular
      smooth muscle cells from RGS2-deficient mice are presented. Results from these
      studies have been used to demonstrate the high relative potency of RGS2 for the
      regulation of Gq signaling at the biochemical, cellular, and physiologic level.

PMID- 15488172
TI  - Analysis of the interaction between RGS2 and adenylyl cyclase.
AB  - Regulators of G-protein signaling (RGS) are a family of highly diverse,
      multifunctional signaling proteins that enhance the intrinsic GTPase rate of
      certain heterotrimeric G-protein alpha subunits. New findings indicate that RGS
      proteins act not only as dedicated G-protein inhibitors, but rather as tightly
      regulated modulators of many aspects of G-protein signaling. Like other RGS
      proteins, RGS2 lacks GTPase-activating protein activity for Gsalpha; however, it
      directly inhibits the activity of several adenylyl cyclase (AC) isoforms. This
      article discusses methods, including AC binding assays, cAMP accumulation assays,
      in vitro AC activity assays, and gel filtration, used to identify the interaction
      site of RGS2 and type V adenylyl cyclase.

PMID- 15488173
TI  - Assays of RGS3 activation and modulation.
AB  - Regulator of G-protein signaling (RGS) proteins accelerate the intrinsic GTPase
      activity of Galpha subunits, terminating G-protein signaling. Although the
      structure and the downstream effectors of RGS proteins have been investigated
      extensively, the mechanisms underlying their activation are still largely
      unexplored. Recent investigations of RGS proteins in intact cells are starting to
      shed some light on this issue. In particular, the retrovirus-mediated
      overexpression of individual RGS3 isoforms showed that activation of RGS3s
      requires Ca2+ binding to an EF-like domain, and such Ca2+ binding promotes the
      rapid desensitization of Go-mediated inhibition of N-type Ca2+ (N) channels. This
      article provides detailed information on the use and power of retrovirus-mediated
      overexpression of RGS proteins in dorsal root ganglion neurons to isolate and
      identify the mechanisms underlying the initiation of RGS3-dependent inhibitory
      activity.

PMID- 15488174
TI  - Analysis of PDZ-RGS3 function in ephrin-B reverse signaling.
AB  - Transmembrane B ephrins and their Eph receptors signal bidirectionally. However,
      the molecular and cellular mechanisms of the "reverse signaling" by B ephrins are
      not fully understood. The identification of several B ephrin cytoplasmic domain
      interacting proteins has begun to shed light on the signal transduction
      mechanisms and the cellular effects of B ephrin reverse signaling. This article
      describes the use of a Transwell migration assay system to characterize the
      function of a PDZ domain and a regulator of G-protein signaling (RGS) domain
      containing protein, PDZ-RGS3, in mediating B ephrin reverse signaling in cultured
      neurons. The Transwell system discussed here can provide an effective cell-based
      assay for elucidating RGS protein-mediated signaling interactions in neurons.

PMID- 15488175
TI  - Biochemical and electrophysiological analyses of RGS8 function.
AB  - RGS8 was identified as a regulator of G-protein signaling (RGS) protein induced
      in neuronally differentiated P19 cells. This article presents methods used to
      estimate the binding activity and selectivity between RGS8 and Galpha subunits.
      It describes three kinds of in vitro-binding experiments using RGS8 proteins
      generated by three different techniques: recombinant protein from Escherichia
      coli, in vitro-translated protein, and protein expressed in cDNA-transfected
      cultured cells. It also presents methods of the functional analysis of RGS
      protein using the Xenopus oocyte expression system. Electrophysiological
      procedures, which were used to examine the effects of RGS8 on Gi- and Gq-mediated
      responses, are described.

PMID- 15488176
TI  - Biochemical purification and functional analysis of complexes between the G
      protein subunit Gbeta5 and RGS proteins.
AB  - Regulator of G-protein signaling (RGS) proteins of the R7 subfamily (RGS6, 7, 9,
      and 11) contain a unique Ggamma-like (GGL) domain that enables their association
      with the G-protein beta subunit Gbeta5. The existence of these complexes was
      demonstrated by their purification from native tissues as well as by
      reconstitution in vitro. According to pulse-chase analysis, Gbeta5 and RGS7
      monomers undergo rapid proteolytic degradation in cells, whereas the dimer is
      stable. Studies of the functional role of Gbeta5-RGS dimers using GTPase
      activity, ion channel, and calcium mobilization assays showed that, similarly to
      other RGS proteins, they can negatively regulate G-protein-mediated signal
      transduction. Protein-protein interactions involving the Gbeta5-RGS7 complex can
      be studied in cells using fluorescence resonance energy transfer utilizing
      Gbeta5, RGS, and Galpha subunits fused to the cyan and yellow versions of green
      fluorescent protein.

PMID- 15488177
TI  - Purification and in vitro functional analysis of R7 subfamily RGS proteins in
      complex with Gbeta5.
AB  - The study of purified regulator of G-protein signaling (RGS) proteins in steady
      state GTPase assays using reconstituted proteoliposomes is a powerful approach to
      characterizing the RGS protein-mediated acceleration of intrinsic Galpha subunit
      GTPase activity in the context of various G-protein and G-protein-coupled
      receptor (GPCR) combinations. This approach has been applied successfully to the
      R7 subfamily of RGS proteins, RGS6, -7, -9, and -11, which form heterodimers with
      Gbeta5 subunits via the G-protein gamma-like domain of R7 proteins. This article
      describes the purification of heterodimers from Sf9 insect cells following the
      expression of recombinant R7 protein and histidine-tagged Gbeta5 using affinity
      and ion-exchange chromatography. The ability of the heterodimers to accelerate
      the intrinsic GTPase activity of Galpha subunits was assessed in steady-state
      GTPase assays performed on proteoliposomes consisting of phospholipids, purified
      G proteins, and purified GPCRs.

PMID- 15488179
TI  - Kinetic approaches to study the function of RGS9 isoforms.
AB  - The experimental strategies developed in kinetic studies of interactions between
      RGS9 isoforms with G proteins of the Gi subfamily provide a useful framework for
      conducting similar studies with essentially any regulator of G-protein signaling
      (RGS) protein-G-protein pair. This article describes two major kinetic approaches
      used in the studies of RGS9 isoforms: single turnover and multiple turnover
      GTPase assays. We also describe pull-down assays as a method complementary to the
      kinetic assays. The discussion of the strengths and limitations of each
      individual assay emphasizes the importance of combining multiple experimental
      approaches in order to obtain comprehensive and internally consistent information
      regarding the mechanisms of RGS protein action.

PMID- 15488178
TI  - Characterization of R9AP, a membrane anchor for the photoreceptor GTPase
      accelerating protein, RGS9-1.
AB  - The proper recovery of photoreceptor light responses requires timely inactivation
      of the G-protein transducin (Gt) by GTP hydrolysis. It is now well established
      that the GTPase-accelerating protein (GAP) RGS9-1 plays an important role in
      determining the recovery kinetics of photoresponses. RGS9-1 has been found to be
      anchored to photoreceptor disk membranes by a novel photoreceptor protein, R9AP.
      R9AP has a single transmembrane domain at its C-terminal region. Membrane
      tethering by R9AP enhances RGS9-1 GAP activity in vitro and has been hypothesized
      to be important for the regulation of RGS9-1 function in vivo. In addition, R9AP
      shows structural similarity to the SNARE complex protein syntaxin and has been
      shown to be required for the correct targeting and localization of the RGS9-1
      protein in photoreceptors. Therefore, R9AP may have additional functions other
      than that in the phototransduction pathway. This article presents methods and
      protocols developed for the functional characterization of R9AP in
      phototransduction, including the immunoprecipitation of the endogenous protein,
      the expression and purification of recombinant proteins, the reconstitution of
      proteoliposomes, and assays for its interaction with RGS9-1 and its effects on
      RGS9-1 GAP activity. These methods may also be applied to the study of R9AP
      function in other pathways or other cell types or to the studies of other
      membrane proteins that are structurally similar to R9AP.

PMID- 15488180
TI  - Assays of nuclear localization of R7/Gbeta5 complexes.
AB  - Heterodimeric complexes between individual members of the R7 subfamily of
      regulators of G-protein signaling proteins and the Gbeta5 isoform of the
      heterotrimeric G-protein beta subunit family are strongly expressed in the cell
      nucleus in neurons and brain, as well as in the cytoplasm and plasma membrane.
      Native and recombinant Gbeta5 and/or R7 expression have been studied in model
      systems like rat pheochromocytoma PC12 cells where their nuclear localization can
      be studied by fluorescence microscopy and/or subcellular fractionation. Nucleic
      acid counterstains chosen for compatibility with the fluorescent tags on
      secondary antibodies can facilitate the assay of R7/Gbeta5 nuclear localization
      by epifluorescence or confocal laser microscopy. Subcellular fractionation allows
      isolation of a purified nuclear fraction that can be probed for the presence of
      Gbeta5 and/or R7 subunits by immunoblots or immunoprecipitation and compared to
      other subcellular fractions. While the function of nuclear R7/Gbeta5 complexes is
      unknown, comparison with the properties of other RGS proteins that localize to
      the cell nucleus may suggest modes of action. Models are offered in which the
      reversible post-translational modification of R7/Gbeta5 complexes regulates their
      nuclear localization and signaling activity, whether the target of such signaling
      activity is in the nucleus, at the plasma membrane, or both.

PMID- 15488181
TI  - Mapping of RGS12-Cav2.2 channel interaction.
AB  - The alpha1 (pore-forming) subunit of the Cav2.2 (N-type) channel is tyrosine
      phosphorylated by Src kinase upon activation of GABAB receptors. The tyrosine
      phosphorylated form of the alpha1 subunit of the Cav2.2 channel becomes a target
      for the binding of RGS12, a GTPase-accelerating protein. Binding of the
      phosphotyrosine-binding domain of RGS12 to the tyrosine-phosphorylated channel
      alters the kinetics of the termination of GABA-mediated inhibition of the calcium
      current. Using a combination of biochemical and electrophysiological approaches,
      we have determined that the SNARE binding or "synprint" region of the Cav2.2
      binds to RGS12. This article describes the protocols used to map the interaction
      using primary neuronal cultures.

PMID- 15488182
TI  - Analysis of interactions between regulator of G-protein signaling-14 and
      microtubules.
AB  - Microtubules are dynamic polymers essential for mitosis and cell division,
      intracellular transport, and maintaining cell organization and structure.
      Microtubule dynamics are tightly controlled in a context-specific manner by a
      myriad of microtubule-associated proteins. We have identified regulator of G
      protein signaling-14 (RGS14) as a microtubule-associated protein. RGS14 is a
      component of the mitotic apparatus that binds directly to and stabilizes
      microtubules in vitro and is essential for the first cell division in the mouse
      embryo. This article describes methods used for examining the impact of the
      RGS14/microtubule interaction in vivo and in vitro.

PMID- 15488184
TI  - Regulation of RGS-RhoGEFs by Galpha12 and Galpha13 proteins.
AB  - Three mammalian Rho guanine nucleotide exchange factors (RhoGEFs), leukemia
      associated RhoGEF (LARG), p115RhoGEF, and PDZ-RhoGEF, contain regulator of G
      protein signaling (RGS) domains within their amino-terminal regions. These
      RhoGEFs link signals from heterotrimeric G12/13 protein-coupled receptors to Rho
      GTPase activation, leading to various cellular responses, such as actin
      reorganization and gene expression. The activity of these RhoGEFs is regulated by
      Galpha12/13 through their RGS domains. Because RhoGEFs stimulate guanine
      nucleotide exchange by Rho GTPases, RhoGEF activation can be measured by
      monitoring GTP binding to or GDP dissociation from Rho GTPases. This article
      describes methods used to perform reconstitution assays to measure the activity
      of RhoGEFs regulated by Galpha12/13.

PMID- 15488183
TI  - Modular architecture and novel protein-protein interactions regulating the RGS
      containing Rho guanine nucleotide exchange factors.
AB  - The regulator of G-protein signaling (RGS)-containing RhoGEFs, including
      p115RhoGEF, PDZ-RhoGEF, and LARG, represent a novel family of guanine nucleotide
      exchange factors for RhoA that are regulated by the Galpha(12/13) family of
      heterotrimeric G proteins. Experimental evidence indicates that the complex
      architecture of these RhoGEFs provides the structural basis for novel regulatory
      mechanisms mediated by protein-protein interactions. These include the direct
      association of their RGS domain with GTP-bound forms of Galpha(12/13) and the
      binding of the PDZ domain present in PDZ-RhoGEF and LARG to plexins, which are
      receptors for semaphorins. The carboxyl-terminal region of these GEFs also exerts
      regulatory properties, including the ability to form dimers, which is inhibitory
      to their in vivo GEF activity and, in the case of PDZ-RhoGEF, to associate with
      PAK4, a downstream target of Cdc42. This carboxyl-terminal region also acts as
      the target for tyrosine kinases, which have a positive effect on the long-term
      activity of these GEFs. This article describes the experimental strategies that
      have been utilized to begin unraveling the molecular mechanisms regulating the
      functional activity of RGS-containing RhoGEFs.

PMID- 15488185
TI  - Analysis of G-protein-coupled receptor kinase RGS homology domains.
AB  - G-protein-coupled receptor kinases (GRKs) specifically phosphorylate agonist
      occupied G-protein-coupled receptors (GPCRs). All seven mammalian GRKs contain an
      N-terminal domain that is homologous to the regulator of G-protein signaling
      (RGS) family of proteins. The RGS domain of GRK2 has been shown to interact
      specifically with Galphaq family members. While the specificity and functional
      consequences of GRK/Galpha interaction remain somewhat poorly defined, GRK RGS
      homology (RH) domains likely function to provide specificity for GRK interaction
      with a particular Galpha subunit or GPCR/Galpha complex. Indeed, GRK2 binds
      Galphaq, alpha11, and alpha14, but not Galpha16, Galphas, Galphai, or
      Galpha(12/13), while the RGS domains of GRK5 and GRK6 do not bind Galpha(q/11),
      Galphas, Galphai, or Galpha(12/13). In this chapter we describe various in vitro
      and intact cell strategies that can be used to elucidate the function of GRK RH
      domains.

PMID- 15488186
TI  - Characterization of GRK2 RH domain-dependent regulation of GPCR coupling to
      heterotrimeric G proteins.
AB  - Heterotrimeric guanine nucleotide (G)-coupled receptors (GPCRs) form the largest
      family of integral membrane proteins. GPCR activation by an agonist promotes the
      exchange of GDP for GTP on the Galpha subunit of the heterotrimeric G protein.
      The dissociated Galpha and Gbetagamma subunits subsequently modulate the activity
      of a diverse assortment of effector systems. GPCR signaling via heterotrimeric G
      proteins is attenuated rapidly by the engagement of protein kinases. The
      canonical model for GPCR desensitization involves G protein-coupled receptor
      kinase (GRK)-dependent receptor phosphorylation to promote the binding of
      arrestin proteins that function to sterically block receptor:G-protein
      interactions. GRK2 and GRK3 have been shown to interact with Galphaq via the
      regulator of G-protein signaling (RGS) homology (RH) domain localized within
      their amino-terminal domains. It now appears that the G-protein uncoupling of
      many GPCRs linked to Galphaq, in particularly metabotropic glutamate receptors,
      may be mediated by the GRK2 RH domain via a phosphorylation-independent
      mechanism. This article reviews much of the background and methodology required
      for the characterization of the GRK2 phosphorylation-independent attenuation of
      GPCR signaling.

PMID- 15488187
TI  - Analysis of differential modulatory activities of GRK2 and GRK4 on Galphaq
      coupled receptor signaling.
AB  - G-protein-coupled receptor kinases (GRK) contain a regulator of G-protein
      signaling (RGS)-like domain located at the N terminus (GRK-Nter) of their
      sequence. This domain is present in all the GRK subtypes, but the RGS-like domain
      of GRK2 was documented to be functionally active, as it is able to interact
      selectively with Galphaq (both in vitro and in cells) and to inhibit Galphaq
      dependent signaling. In contrast GRK4, GRK5, and GRK6 are unable to interact with
      Galphaq. This article describes the methodology to investigate the modulatory
      activity of GRK2 and GRK4 on GPCR-stimulated Galphaq signaling. This analysis is
      essentially based on three types of experiments: (a) study of the effect of the
      GRK-Nter on GPCR-dependent signaling; (b) analysis of the binding of GRK-Nter to
      Galphaq in vitro; and (c) analysis of the interaction of GRK with Galphaq in
      cells.

PMID- 15488188
TI  - Identification and functional analysis of dual-specific A kinase-anchoring
      protein-2.
AB  - Since the cloning of dual-specificity A kinase-anchoring protein 2 (D-AKAP2),
      there has been considerable progress in understanding the structural features of
      this AKAP and its interaction with protein kinase A (PKA). The domain
      organization of D-AKAP2 is quite unique, containing two tandem, putative RGS
      domains, a PKA-binding motif, and a PDZ (PSD95/Dlg/ZO1)-binding motif. Although
      the function of D-AKAP2 has remained elusive, several reports suggest that D
      AKAP2 is targeted to cotransporters in the kidney and that it may play a role in
      regulating transporter activity. In addition, the finding that a single
      nucleotide polymorphism in the PKA-binding region of D-AKAP2 may contribute to
      increased morbidity and mortality emphasizes the potential importance of this
      protein in pathogenesis. The first part of this article focuses on initial
      efforts to identify and clone D-AKAP2, followed by tissue localization and
      expression profiles. The latter half of the article focuses on the domain
      organization of D-AKAP2 and its interaction with PKA. Finally, a comprehensive
      analysis of the PKA binding motif is described, which has led to the development
      of novel peptides derived from D-AKAP2 that can be useful tools in probing the
      function of this AKAP in cellular and animal models.

PMID- 15488189
TI  - Purification and functional analysis of Ric-8A: a guanine nucleotide exchange
      factor for G-protein alpha subunits.
AB  - Ric-8A (synembryn) has been shown to accelerate the in vitro guanine nucleotide
      exchange activities of most G-protein alpha subunits (with the exception of
      Galphas). Methods are presented in this article for the purification of Ric-8A
      and functional analysis of the effects Ric-8A has on G-protein alpha subunit
      guanine nucleotide-binding activities. The use of Ric-8A to prepare GTPgammaS
      Galpha and nucleotide-free Galpha (in complex with Ric-8A) is described.

PMID- 15488190
TI  - Tubulin as a regulator of G-protein signaling.
AB  - Tubulin is known to form high-affinity complexes with certain G proteins. The
      formation of such complexes allows tubulin to activate Galpha and fosters a
      system whereby elements of the cytoskeleton can influence G-protein signaling.
      This article describes the interaction between tubulin and G proteins and
      discusses methods for examining this interaction.

PMID- 15488191
TI  - Nucleoside diphosphate kinase-mediated activation of heterotrimeric G proteins.
AB  - Formation of GTP by nucleoside diphosphate kinase (NDPK) can contribute to
      receptor independent G protein activation. Apparently, the NDPK B isoform forms
      complexes with Gbetagamma dimers and thereby phosphorylates His266 in Gbeta1
      subunits. Phosphorylated His266 mediates G protein activation by a transfer of
      the high energetic phosphate onto GDP, thus leading to de novo synthesis of GTP.
      Moreover, it has been demonstrated that the sarcolemmal content of NDPK isoforms
      is increased in hearts with terminal congestive heart failure leading to enhanced
      G protein activation. Similar data were reported in a rat model for beta
      adrenoceptor-induced cardiac hypertrophy. We therefore describe in this chapter
      several methods which can be used for analysis of NDPK mediated G protein
      activation: (1) The quantification of NDPK isoforms in highly purified cardiac
      sarcolemmal membranes, (2) the enrichment of the NDPK B/Gbetagamma-complex from
      preparations of the retinal G protein transducin, (3) the analysis of the
      enhanced NDPK activated and high energy phosphate transfer in a neonatal rat
      cardiac myocyte derived cell line stably overexpressing NDPK (H10 cells), and (4)
      the increased activation of adenylyl cyclase by the enhanced receptor-independent
      activation of the stimulatory G protein alpha subunit in these cells.

PMID- 15488192
TI  - Purification and in vitro functional analyses of RGS12 and RGS14 GoLoco motif
      peptides.
AB  - The GoLoco motif is a short polypeptide sequence that binds to heterotrimeric G
      protein alpha subunits of the adenylyl cyclase-inhibitory (Galpha(i/o)) subclass
      in a nucleotide-dependent manner (i.e., solely to the GDP-bound ground state).
      This article describes methods used for the expression, purification, and in
      vitro evaluation of membrane-permeant tag fusion peptides derived from the GoLoco
      motif regions of "regulator of G-protein signaling" proteins type 12 (RGS12) and
      14 (RGS14) and a consensus GoLoco sequence from the multiple GoLoco motif protein
      AGS3. Three different fluorescence-based assays are described for evaluating the
      in vitro function of these GoLoco peptides as guanine nucleotide dissociation
      inhibitors, including measurements of GTPgammaS binding and Galpha subunit
      activation by the planar ion aluminum tetrafluoride.

PMID- 15488193
TI  - GoLoco motif peptides as probes of Galpha subunit specificity in coupling of G
      protein-coupled receptors to ion channels.
AB  - Biochemical and structural studies of signaling proteins have revealed critical
      features of peptide motifs at the interaction surfaces between proteins. Such
      information can be used to design small peptides that can be used as functional
      probes of specific interactions in signaling cascades. This article describes the
      use of a novel domain (the GoLoco motif) found in several members of the
      regulators of G-protein signaling (RGS) protein family to probe the specificity
      of Galpha subunit involvement in the coupling of dopamine and somatostatin
      receptors to ion channels in the AtT20 neuroendocrine cell line. Peptides
      encoding the GoLoco motifs of RGS12 and AGS3 were perfused into single cells
      during electrical recording of agonist-induced current responses by whole cell
      patch clamp methods. The particular sequences chosen have been demonstrated to
      bind selectively to the GDP-bound form of Galphai, but not Galphao, and preclude
      association of Gbetagamma and Galphai subunits. A functional manifestation of
      this property is observed in the progressive uncoupling of D2 dopamine receptors
      and Kir3.1/3.2 channels with repeated agonist application. Similar uncoupling is
      not observed with somatostatin receptors nor with D2 receptors coupling to
      calcium channels, suggesting Galpha subunit specificity in these signaling
      pathways. Motifs found in other proteins in the GPCR signaling machinery may also
      prove useful in assessing G-protein signaling specificity and complexity in
      single cells in the future.

PMID- 15488194
TI  - Experimental systems for studying the role of G-protein-coupled receptors in
      receptor tyrosine kinase signal transduction.
AB  - Early conception of G-protein-coupled receptor (GPCR) and receptor tyrosine
      kinase (RTK) signaling pathways was that each represented distinct and linear
      modules that converged on downstream targets, such as p42/p44 mitogen-activated
      protein kinase (MAPK). It has now become clear that this is not the case and that
      multiple levels of cross-talk exist between both receptor systems at early points
      during signaling events. In recent years, it has become apparent that
      transactivation of receptor tyrosine kinases by GPCR agonists is a general
      phenomenon that has been demonstrated for many unrelated GPCRs and receptor
      tyrosine kinases. In this case, GPCR/G-protein participation is upstream of the
      receptor tyrosine kinase. However, evidence now demonstrates that numerous growth
      factors use G proteins and associated signaling molecules such as beta-arrestins
      that participate downstream of the receptor tyrosine kinase to signal to
      effectors, such as p42/p44 MAPK. This article highlights experimental approaches
      used to investigate this novel mechanism of cross-talk between receptor tyrosine
      kinases and GPCRs.

PMID- 15488195
TI  - Identification and biochemical analysis of GRIN1 and GRIN2.
AB  - We have identified the novel Galphaz-binding protein, which is referred to as the
      G-protein-regulated inducer of neurite outgrowth (GRIN1) using the far-western
      method. GRIN1 is expressed specifically in brain and binds preferentially to the
      activated form of alpha subunits of Gz, Gi, and Go. Coexpression of GRIN1 and the
      activated form of Galphao induce neurite outgrowth in Neuro2a cells. We have
      further identified two human GRIN1 homologs, GRIN2 and GRIN3, in the database.
      This article shows that GRIN2 can also bind to the GTP-bound form of Galphao.
      These findings suggest that the GRIN1 family may function as a downstream
      effector for Galphao to regulate neurite growth.

PMID- 15488196
TI  - NIH research: widening access, building collaboration.

PMID- 15488197
TI  - Vaccine preparedness, or not.

PMID- 15488198
TI  - First childbirth from transplanted cryopreserved ovarian tissue brings hope for
      cancer survivors.

PMID- 15488199
TI  - Vaccine efficacy: winning a battle (not war) against malaria.

PMID- 15488200
TI  - Competency in the age of assessment.

PMID- 15488201
TI  - Panda phlebotomies? The need for comparative screening for haemochromatosis.

PMID- 15488203
TI  - Chlamydia, gonorrhoea, and injectable progesterone.

PMID- 15488202
TI  - Hepatitis C NS3 helicase unwinds RNA in leaps and bounds.

PMID- 15488204
TI  - Is wound healing a true science or a clinical art?

PMID- 15488205
TI  - The marketing of asthma and allergies.

PMID- 15488206
TI  - Setting of clinical standards.

PMID- 15488207
TI  - Setting of clinical standards.

PMID- 15488208
TI  - Setting of clinical standards.

PMID- 15488209
TI  - Should we trust results of meta-analyses?

PMID- 15488210
TI  - Should we trust results of meta-analyses?

PMID- 15488212
TI  - Should we trust results of meta-analyses?

PMID- 15488213
TI  - Autoantibodies as predictors of disease.

PMID- 15488214
TI  - Africa's children orphaned by AIDS.

PMID- 15488215
TI  - Livebirth after orthotopic transplantation of cryopreserved ovarian tissue.
AB  - BACKGROUND: The lifesaving treatment endured by cancer patients leads, in many
      women, to early menopause and subsequent infertility. In clinical situations for
      which chemotherapy needs to be started, ovarian tissue cryopreservation looks to
      be a promising option to restore fertility. In 1997, biopsy samples of ovarian
      cortex were taken from a woman with stage IV Hodgkin's lymphoma and cryopreserved
      before chemotherapy was initiated. After her cancer treatment, the patient had
      premature ovarian failure. METHODS: In 2003, after freeze-thawing, orthotopic
      autotransplantation of ovarian cortical tissue was done by laparoscopy. FINDINGS:
      5 months after reimplantation, basal body temperature, menstrual cycles, vaginal
      ultrasonography, and hormone concentrations indicated recovery of regular
      ovulatory cycles. Laparoscopy at 5 months confirmed the ultrasonographic data and
      showed the presence of a follicle at the site of reimplantation, clearly situated
      outside the ovaries, both of which appeared atrophic. From 5 to 9 months, the
      patient had menstrual bleeding and development of a follicle or corpus luteum
      with every cycle. 11 months after reimplantation, human chorionic gonadotrophin
      concentrations and vaginal echography confirmed a viable intrauterine pregnancy,
      which has resulted in a livebirth. INTERPRETATION: We have described a livebirth
      after orthotopic autotransplantation of cryopreserved ovarian tissue. Our
      findings suggest that cryopreservation of ovarian tissue should be offered to all
      young women diagnosed with cancer.

PMID- 15488216
TI  - Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and
      disease in young African children: randomised controlled trial.
AB  - BACKGROUND: Development of an effective malaria vaccine could greatly contribute
      to disease control. RTS,S/AS02A is a pre-erythrocytic vaccine candidate based on
      Plasmodium falciparum circumsporozoite surface antigen. We aimed to assess
      vaccine efficacy, immunogenicity, and safety in young African children. METHODS:
      We did a double-blind, phase IIb, randomised controlled trial in Mozambique in
      2022 children aged 1-4 years. The study included two cohorts of children living
      in two separate areas which underwent different follow-up schemes. Participants
      were randomly allocated three doses of either RTS,S/AS02A candidate malaria
      vaccine or control vaccines. The primary endpoint, determined in cohort 1
      (n=1605), was time to first clinical episode of P falciparum malaria (axillary
      temperature > or =37.5 degrees C and P falciparum asexual parasitaemia >2500 per
      microL) over a 6-month surveillance period. Efficacy for prevention of new
      infections was determined in cohort 2 (n=417). Analysis was per protocol.
      FINDINGS: 115 children in cohort 1 and 50 in cohort 2 did not receive all three
      doses and were excluded from the per-protocol analysis. Vaccine efficacy for the
      first clinical episodes was 29.9% (95% CI 11.0-44.8; p=0.004). At the end of the
      6-month observation period, prevalence of P falciparum infection was 37% lower in
      the RTS,S/AS02A group compared with the control group (11.9% vs 18.9%; p=0.0003).
      Vaccine efficacy for severe malaria was 57.7% (95% CI 16.2-80.6; p=0.019). In
      cohort 2, vaccine efficacy for extending time to first infection was 45.0% (31.4
      55.9; p<0.0001). INTERPRETATION: The RTS,S/AS02A vaccine was safe, well
      tolerated, and immunogenic. Our results show development of an effective vaccine
      against malaria is feasible.

PMID- 15488217
TI  - Prevalence of mental incapacity in medical inpatients and associated risk
      factors: cross-sectional study.
AB  - BACKGROUND: Although mental incapacity is becoming increasingly important in
      clinical practice, little information is available on its frequency in medical
      inpatients. We aimed to estimate the prevalence of mental incapacity in acutely
      admitted medical inpatients; to determine the frequency that medical teams
      recognised patients who did not have mental capacity; and to identify factors
      associated with mental incapacity. METHODS: Over an 18-month period, we recruited
      302 consecutive acute medical inpatients. Participants were assessed with the
      MacArthur competence tool for treatment and by clinical interview. Cognitive
      impairment was measured by the mini-mental state examination. FINDINGS: 72 (24%)
      patients were severely cognitively impaired, unconscious, or unable to express a
      choice and were automatically assigned to the incapacity group. 71 (24%) refused
      to participate or could not speak English. Thus, 159 patients were interviewed.
      Of these, 31% (95% CI 24-38) were judged not to have mental capacity. For the
      total sample (n=302), we estimated that at least 40% did not have mental
      capacity. Clinical teams rarely identified patients who did not have mental
      capacity: of 50 patients interviewed, 12 (24%) were rated as lacking capacity.
      Factors associated with mental incapacity were increasing age and cognitive
      impairment. INTERPRETATION: Mental incapacity is common in acutely ill medical
      inpatients, and clinicians tend not to recognise it. Screening methods for
      cognitive impairment could be useful in detecting those with doubtful capacity to
      consent.

PMID- 15488218
TI  - Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and
      viral load in HIV infection in rural Uganda.
AB  - BACKGROUND: Prophylaxis with co-trimoxazole (trimethoprim-sulphamethoxazole) is
      recommended for people with HIV infection or AIDS but is rarely used in Africa.
      We assessed the effect of such prophylaxis on morbidity, mortality, CD4-cell
      count, and viral load among people with HIV infection living in rural Uganda, an
      area with high rates of bacterial resistance to co-trimoxazole. METHODS: Between
      April, 2001, and March, 2003, we enrolled, and followed up with weekly home
      visits, 509 individuals with HIV-1 infection and their 1522 HIV-negative
      household members. After 5 months of follow-up, HIV-positive participants were
      offered daily co-trimoxazole prophylaxis (800 mg trimethoprim, 160 mg
      sulphamethoxazole) and followed up for a further 1.5 years. We assessed rates of
      malaria, diarrhoea, hospital admission, and death. FINDINGS: Co-trimoxazole was
      well tolerated with rare (<2% per person-year) adverse reactions. Even though
      rates of resistance in diarrhoeal pathogens were high (76%), co-trimoxazole
      prophylaxis was associated with a 46% reduction in mortality (hazard ratio 0.54
      [95% CI 0.35-0.84], p=0.006) and lower rates of malaria (multivariate incidence
      rate ratio 0.28 [0.19-0.40], p<0.0001), diarrhoea (0.65 [0.53-0.81], p<0.0001),
      and hospital admission (0.69 [0.48-0.98], p=0.04). The annual rate of decline in
      CD4-cell count was less during prophylaxis than before (77 vs 203 cells per
      microL, p<0.0001), and the annual rate of increase in viral load was lower (0.08
      vs 0.90 log(10) copies per mL, p=0.01). INTERPRETATION: Daily co-trimoxazole
      prophylaxis was associated with reduced morbidity and mortality and had
      beneficial effects on CD4-cell count and viral load. Co-trimoxazole prophylaxis
      is a readily available, effective intervention for people with HIV infection in
      Africa.

PMID- 15488220
TI  - Eyelid oedema and headache.

PMID- 15488219
TI  - Association between mutations in a thyroid hormone transporter and severe X
      linked psychomotor retardation.
AB  - Monocarboxylate transporter 8 (MCT8) is a thyroid hormone transporter, the gene
      of which is located on the X chromosome. We tested whether mutations in MCT8
      cause severe psychomotor retardation and high serum triiodothyronine (T3)
      concentrations in five unrelated young boys. The coding sequence of MCT8 was
      analysed by PCR and direct sequencing of its six exons. In two patients, gene
      deletions of 2.4 kb and 24 kb were recorded and in three patients missense
      mutations Ala150Val, Arg171 stop, and Leu397Pro were identified. We suggest that
      this novel syndrome of X-linked psychomotor retardation is due to a defect in T3
      entry into neurons through MCT8, resulting in impaired T3 action and metabolism.

PMID- 15488221
TI  - The eye in systemic infection.
AB  - Bacterial, fungal, viral, and parasitic pathogens all cause systemic infection
      and can spread to the eye. Dissemination of pathogens via the bloodstream can
      lead to direct involvement of the eye. Visual loss is common in bacterial or
      fungal endophthalmitis, and toxoplasmosis is a major cause of ocular morbidity
      and poor vision after congenital or acquired infection. Some infections cause
      intraocular damage by indirect mechanisms (eg, HIV-mediated immunosuppression),
      leading to opportunistic infections such as cytomegalovirus infection, periocular
      nerve involvement due to leprosy, and hypersensitivity reactions in tuberculosis.
      Eye symptoms might indicate the outcome of an underlying infection, such as
      development of retinal ischaemia in severe malaria, which is associated with a
      poor prognosis. Successful outcome for patients with ocular infection depends on
      close collaboration between clinicians identifying and treating underlying
      disease, specialist ophthalmic review, and ophthalmic interventional skills (when
      needed).

PMID- 15488222
TI  - How to bridge the gap in human resources for health.
AB  - Human resources are the crucial core of a health system, but they have been a
      neglected component of health-system development. The demands on health systems
      have escalated in low income countries, in the form of the Millennium Development
      Goals and new targets for more access to HIV/AIDS treatment. Human resources are
      in very short supply in health systems in low and middle income countries
      compared with high income countries or with the skill requirements of a minimum
      package of health interventions. Equally serious concerns exist about the quality
      and productivity of the health workforce in low income countries. Among available
      strategies to address the problems, expansion of the numbers of doctors and
      nurses through training is highly constrained. This is a difficult issue
      involving the interplay of multiple factors and forces.

PMID- 15488223
TI  - Prescribing sentence: time for evidence-based justice.

PMID- 15488224
TI  - A hint from the past.

PMID- 15488225
TI  - Evaluation of animal models of Parkinson's disease for neuroprotective
      strategies.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder characterized by
      the progressive loss of dopaminergic nigral neurons and striatal dopamine.
      Despite the advances of modern therapy to treat the symptoms of PD, most of the
      patients will eventually experience debilitating disability. The need for
      neuroprotective strategies that will slow or stop the progression of the disease
      is clear. The progress in the understanding of the cause and pathogenesis of PD
      is providing clues for the development of disease-modifying strategies. In that
      regard, animal models of PD and non-human primate models in particular, are
      essential for the preclinical evaluation and testing of candidate therapies.
      However, the diversity of models and different outcome measures used by
      investigators make it challenging to compare results between neuroprotective
      agents. In this review we will discuss methods for the selection, development and
      assessment of animal models of PD, the role of non-human primates and the concept
      of "multiple models/multiple endpoints" to predict the success in the clinic of
      neuroprotective strategies.

PMID- 15488226
TI  - Monitoring real-time release of ATP from the molluscan central nervous system.
AB  - The further understanding of neuronal function is imperative for the prevention
      and treatment of neurofunctional disorders. To aid in this realization, novel
      methods for monitoring neuronal cell function must be developed and
      characterized. In this study, we report the application of real-time imaging of
      luciferase-catalyzed ATP chemiluminescence for the investigation of ATP release
      from whole central nervous systems of the freshwater snail Lymnaea stagnalis.
      Release of ATP from Lymnaea ganglia varied among the different ganglia as well as
      within individual ganglia. Furthermore, the magnitude of ATP release varied
      following the stimulation of neurons with common neurotransmitters.

PMID- 15488227
TI  - Measurement of pre- and post-synaptic proteins in cerebral cortex: effects of
      post-mortem delay.
AB  - Assessments of synaptic density in human brain are often based on measurements of
      synaptic proteins. Little information is available on their post-mortem
      stability. We have investigated this by ELISAs of the pre-synaptic proteins
      syntaxin and synaptophysin, and the post-synaptic protein PSD-95, in rat and
      human cortex. The rat brains were cooled in situ from 37 to 20 or 4 degrees C
      over 3 h, and then kept at 20 or 4 degrees C for a further 24-72 h, to simulate
      post-mortem storage at room temperature or in a mortuary refrigerator.
      Synaptophysin and PSD-95 levels in rat cerebral cortex were not significantly
      decreased after 72 h of incubation at 20 degrees C. Syntaxin was stable for 24 h
      but decreased by 39-44% at 48-72 h. Storage at 4 degrees C resulted in a similar
      reduction of syntaxin levels over 72 h. In human brain tissue from 160 people
      aged 24-102 years, post-mortem delay had little effect on synaptic protein levels
      in superior temporal cortex, but was associated with a decline in PSD-95 and
      syntaxin in mid-frontal cortex after 24 h. The more robust stability of
      synaptophysin may be related to its multi-transmembrane structure.

PMID- 15488228
TI  - Accuracy and stability of temperature probes for intracranial application.
AB  - Intracranial temperature measurement may play a pivotal role for prognosis and
      treatment of neurological and neurosurgical patients. For reliable clinical
      application, accurate temperature readings are therefore necessary. We present an
      independent in vitro study investigating the accuracy and stability of three
      temperature probes. Eight Neurovent-P Temp (RN), eight Licox temperature sensors
      (LT) and eight Neurotrend sensors (NT) were placed into a water bath. The
      temperature was increased in 3 degrees C increments from 30 to 42 degrees C
      before (accuracy test day 0) and after (accuracy test day 5) a long-term
      stability test run at 37 +/- 0.2 degrees C. The accuracy tests revealed
      deviations of <0.25, <0.2 and >0.4 degrees C for the RN, NT and LT probes,
      respectively, when compared to the reference measurement by a precision Pt100
      temperature measuring instrument. All sensor types showed stable readings over
      the course of 120 h. The high variability of LT probes was due to a
      malfunctioning Licox monitor. Excluding these values reduced deviation below 0.21
      degrees C the standard deviation at each temperature step was below +/-0.08 (RN,
      NT) and +/-0.12 (LT), laying within the range provided by the manufacturer (RN,
      NT: +/-0.1; LT: +/-0.2). In general, RN, NT and LT temperature measurement is
      reliable, but malfunctioning parts may lead to false interpretation of
      temperature readings. Therefore, validation of temperature probes to a reference
      temperature prior to clinical use is recommended.

PMID- 15488229
TI  - Imaging cocaine-induced changes in the mesocorticolimbic dopaminergic system of
      conscious rats.
AB  - Functional magnetic resonance imaging (fMRI) was used to assess the effects of
      cocaine on brain activation in fully conscious rats. Methods were developed to
      image cocaine-induced changes in blood-oxygen-level-dependent (BOLD) signal
      without the peripheral cardiac and respiratory complications associated with
      psychostimulant administration. Using spin echo planar imaging (EPI), conscious
      rats were imaged in a 4.7 T spectrometer prior to and following the
      intracerebroventricular injection of cocaine (20 microg) in artificial
      cerebrospinal fluid (10 uL). Within 5 min of injection, there was a significant
      increase in BOLD signal intensity in the substantia nigra, ventral tegmental
      area, nucleus accumbens, dorsal striatum and prefrontal cortex, as compared to
      vehicle controls. Minimal negative BOLD signal changes were observed in response
      to cocaine and no significant perturbations in normal cardiovascular and
      respiratory function. These findings demonstrate the technical feasibility of
      studying psychostimulant-induced brain activity using functional MRI in conscious
      rats.

PMID- 15488230
TI  - Extracting burst and tonic components from surface electromyograms in dystonia
      using adaptive wavelet shrinkage.
AB  - The compound surface electromyograms (EMGs) recorded from patients with dystonia
      commonly contains superimposed bursting and tonic activity representing various
      motor symptoms. It is desirable to differentially extract them from the compound
      EMGs so that different symptoms can be more specifically investigated and
      different mechanisms revealed. A non-linear denoising approach based on wavelet
      transformation was investigated by applying soft thresholding to the wavelet
      coefficients. Thresholds were determined according to three different principles
      and two models. Different techniques for wavelet shrinkage were investigated for
      separating burst and tonic activity in the compound EMGs. The combination of
      Stein's unbiased risk estimate principle with a non-white noise model proved
      optimal for separating burst and tonic activity. These turned out to be
      exponentially related; and the temporal relationships between antagonist muscle
      contractions could now be seen clearly. We conclude that adaptive soft
      thresholding wavelet shrinkage provides effective separation of burst and tonic
      activity in the compound EMG in dystonia. This separation should improve our
      understanding of the pathophysiology of dystonia.

PMID- 15488231
TI  - Quantifying the contribution of arm postural tremor to the outcome of goal
      directed pointing task by displacement measures.
AB  - A method for quantifying the outcome of goal-directed postural pointing was
      presented and used for relating the tremor output to the oscillations of single
      arm landmarks. The displacement of reflective markers placed on shoulder, upper
      arm, forearm, and hand were measured by an optoelectronic motion capture system
      in nine subjects holding a laser penlight pointed at a target. The high signal-to
      noise ratio of the measured displacement series (from 7:1 for shoulder marker to
      30:1 for hand marker) demonstrated the feasibility of the proposed system to
      carry out tremor analysis. The track of the laser emission on the target,
      reconstructed from penlight displacements, was studied as the outcome of the
      pointing task. By measuring the length and the dispersion of the path covered by
      the target track in 30 s, a significant and comparable tremor amplitude was found
      in vertical and lateral directions. The correlation between target track and arm
      tremor was stronger for distal than for proximal markers. Spectral and cross
      spectral analyses evidenced the presence of a dominant low frequency oscillation
      (1.5 Hz), along with a high frequency one (5-7 Hz), in the displacement of the
      target track. These two components were significantly linked to the oscillations
      of the hand, the forearm and the upper arm but not to those of the shoulder,
      suggesting that the oscillations in the overall tremor output during the pointing
      task are mainly generated by the arm segments.

PMID- 15488232
TI  - Subcutaneous administration of nimodipine improves bioavailability in rabbits.
AB  - We compared subcutaneous and oral methods of nimodipine administration to
      determine a method of nimodipine administration that maintained serum levels at
      or above the optimal therapeutic concentration (7 ng/ml). Plasma concentrations
      of nimodipine were measured in New Zealand White rabbits (2.6-3.9 kg). First,
      peak plasma concentration (C(max)), time to reach peak plasma concentration
      (T(max)), and area under the curve (AUC) parameters were calculated and compared
      between animals receiving oral or subcutaneous nimodipine (5-15 mg/kg). Next,
      plasma concentrations were measured 24 h after subcutaneous administration of 2.5
      mg/kg of nimodipine in healthy animals and animals with experimentally induced
      SAH. C(max), T(max) and AUC parameters were significantly greater for
      subcutaneous compared to oral nimodipine administration, irrespective of dose.
      Mean nimodipine concentrations at 24 h were >7 ng/ml in both healthy animals
      (12.9 +/- 10.0 ng/ml) and in animals with SAH (11.8 +/- 4.6 ng/ml) that received
      2.5 mg/kg of subcutaneous nimodipine. In this model, the subcutaneous method of
      nimodipine administration consistently maintains plasma levels at or above the
      optimal therapeutic concentration, whereas oral administration fails to do so.

PMID- 15488233
TI  - Infarct volume quantification in mouse focal cerebral ischemia: a comparison of
      triphenyltetrazolium chloride and cresyl violet staining techniques.
AB  - Triphenyltetrazolium chloride (TTC) and cresyl violet (CV) staining are routinely
      used methods to determine cerebral infarct volume and area. In this study, we
      compared these staining techniques using the mouse middle cerebral artery
      occlusion (MCAO) model of focal ischemia. Male C57BL6 mice were subjected to a 90
      min transient MCAO and sacrificed at 24 h reperfusion. Sham operated mice served
      as controls. Two millimeters coronal brain slices were cut at +1.3, -0.7, -2.7
      and -4.7 mm from bregma. The sections were stained with 2% TTC for 20 min and the
      caudal face of each slice was scanned with a flatbed scanner. The sections were
      kept in 4% paraformaldehyde solution for 4 weeks (the solution was changed every
      week). The slices were cryosectioned (40 microm thick), mounted on slides and
      stained with CV and scanned. The infarct volume and area were measured by the
      image-J program for both the staining techniques. There was no significant
      difference in either infarct area or volume between the TTC and CV stained
      sections (P > 0.05). TTC and CV staining showed a high degree of correlation in
      infarct area and volume indicating that both methods are suitable for producing
      accurate measurements of cerebral experimental infarcts.

PMID- 15488234
TI  - A standardized method for brain-cutting suitable for both stereology and MRI
      brain co-registration.
AB  - We have developed an agar-embedding method for brain-slicing that minimizes the
      geometrical distortions which arise from handling and slicing the fixed
      postmortem brain. To facilitate postmortem brain-magnetic resonance imaging (MRI)
      co-registration, each hemisphere is processed separately. We embed the fixed
      brain hemisphere with reference markers in agar. The block containing the brain
      and markers is sliced at a fixed interval using a rotary slicer. Each slice is
      photographed with a high-resolution digital camera. The digital images are
      realigned as a 3-dimensional volume via a control point-based registration method
      for multi-slice registration. The realigned multiple slices of the reconstructed
      postmortem hemisphere are then co-registered to corresponding slices of an in
      vivo reference MRI-volume. We illustrate these postmortem MRI-brain co
      registration methods to correlate in vivo T2-weighted MRI hyperintensities in
      gray and white matter with underlying pathology. For design-based stereology, the
      volume of interest (VOI) is defined using reproducible anatomical boundaries.
      This method is suitable for stereologic measures of structures ranging from
      defined nuclei to whole brain.

PMID- 15488235
TI  - Morphometry of cervical segments grey matter in the male rat spinal cord.
AB  - The cervical portion of the spinal cord is an area frequently affected by
      alterations of medical and veterinary importance. Since there is scarce
      quantitative anatomical data on this region, we undertook a morphometric study of
      the grey matter of all segments of the rat cervical spinal cord of male rats in
      order to generate reference patterns to be used in future experimental studies.
      Using image analysis software, the total spinal cord length and grey and white
      matter area of each segment was recorded. The morphometric characteristics of the
      neurones populating the laminae of the grey matter of the cervical segments was
      also recorded. Neurones were classified into small, medium and large sizes for
      each lamina and statistically compared. The present data fill an anatomical
      information gap by providing quantitative data about the normal anatomical
      features of the rat cervical cord. The anatomical data found could be used to
      better understand the physiological relevance of that region in the rat.

PMID- 15488236
TI  - Automatic recognition of alertness level by using wavelet transform and
      artificial neural network.
AB  - We propose a novel method for automatic recognition of alertness level from full
      spectrum electroencephalogram (EEG) recordings. This procedure uses power
      spectral density (PSD) of discrete wavelet transform (DWT) of full spectrum EEG
      as an input to an artificial neural network (ANN) with three discrete outputs:
      alert, drowsy and sleep. The error back propagation neural network is selected as
      a classifier to discriminate the alertness level of a subject. EEG signals were
      obtained from 30 healthy subjects. The group consisted of 14 females and 16 males
      with ages ranging from 18 to 65 years and a mean age of 33.5 years, and a body
      mass index (BMI) of 32.4 +/- 7.3 kg/m2. Alertness level and classification
      properties of ANN were tested using the data recorded in 12 healthy subjects,
      whereby the EEG recordings were not used been used to train the ANN. The
      statistics were used as a measure of potential applicability of the ANN. The
      accuracy of the ANN was 96 +/- 3% alert, 95 +/- 4% drowsy and 94 +/- 5% sleep.
      The results suggest that the automatic recognition algorithm is applicable for
      distinguishing between alert, drowsy and sleep state in recordings that have not
      been used for the training.

PMID- 15488237
TI  - Overexpression of genes in Purkinje cells in the embryonic chicken cerebellum by
      in vivo electroporation.
AB  - In cerebellar development, Purkinje cells transiently express various genes,
      whose expression is compartmentalized into different mediolaterial or
      parasagittal domains. The study of these genes will help us to understand the
      functional organization of the cerebellum. In the present work, we establish an
      efficient in vivo electroporation technique to transfer genes into Purkinje cells
      of the developing chicken cerebellum, as demonstrated by green fluorescent
      protein. This method can be applied to analyze gene function and regulation in
      cerebellar Purkinje cells.

PMID- 15488238
TI  - Quantifying postural tremor in workers exposed to low levels of manganese.
AB  - The aim of this study was: (1) To determine the minimum number of characteristics
      necessary to discriminate between postural tremor recorded in control subjects
      (CO), in subjects exposed to manganese (MN), and in patients with Parkinson's
      disease (PD), and (2) to examine the continuum of changes between the three
      groups examined. Workers previously exposed to Mn (n = 10), patients with PD (n =
      10), and control subjects (CO) (n = 11) underwent a clinical examination. Blood
      Mn was measured at the end of exposure time for the MN group and 12 months later
      at the beginning of the experiment for all groups. Postural tremor with visual
      feedback was recorded in the index finger with a laser system. Statistical
      criteria were used to reduce computed tremor characteristics to a minimal set of
      reliable discriminating variables. Two variables were retained namely corrected
      wobble (CW), describing the morphology of the tremor oscillations, and
      variability ratio (VR), describing proportional power of tremor. Both variables
      had an overall correct classification rate of 77.4%. Blood Mn levels at the time
      of the experiment were similar for all groups and had insignificant correlation
      with tremor variables. However, blood Mn levels in workers which were also
      measured at the end of exposure time (i.e., 12 months before) showed significant
      correlation (Spearman's rank coefficient) with both harmonic index (rho = 0.70, P
      = 0.03) and first maximum of the autocorrelation function (rho = 0.89, P =
      0.001). We conclude that (1) the tremor of workers exposed to Mn could be
      adequately described with only two variables; (2) a continuum of changes between
      tremor recorded in control subjects, in subjects exposed to Mn and in patients
      with PD was observed, with the MN group always found in between the control (CO)
      and the PD groups; (3) while blood Mn levels in workers were back at control
      levels at the time of the experiment, the effect of Mn on postural tremor was
      still detected. Thus our method has the potential to detect the effect of Mn on
      tremor with only two variables even after Mn level in the blood is back to normal
      values.

PMID- 15488239
TI  - Tetracycline-inducible expression systems for the generation of transgenic
      animals: a comparison of various inducible systems carried in a single vector.
AB  - The most often used tetracycline-regulated transgenic mice system requires the
      generation of two transgenic strains, one carrying an inducible promoter and the
      other a transactivator. In this study, we report the design of a universal and
      simplified regulatory gene delivery vector to facilitate the generation of
      conditional transgenic animals that integrate both the tetracycline regulatory
      and response elements in a single vector. The newly developed tetracycline
      reversed transactivator rtTA-M2 was used in all our constructs, based on its
      highly improved properties with respect to specificity, stability and
      inducibility. To minimize interference between the different tetracycline
      inducible promoters used in this study (tetracycline-responsive element (TRE),
      TRE-tight, or Tk-tetO) and the rtTA-M2 transactivator, both elements were cloned
      in opposite directions and separated by a 5 kb human p53 intron. The
      functionality of this system was confirmed after in vitro transfection in a
      mammalian cell line. Overall induction by the tetracycline-responsive element
      promoter was significantly higher than that induced by the newly developed TRE
      tight promoter. However, the TRE-tight promoter showed a significantly tighter
      expression with minimal background, and still maintained high induction levels.
      The minimal Tk-tetO promoter showed a very weak induction capacity. Our study
      demonstrates that this combination of elements, placed in a single vector is
      sufficient for delivering a functional tetracycline-inducible system to a
      mammalian cell line. Moreover, additional modifications to this regulatory gene
      delivery system, such as the introduction of specific cloning sites and selection
      markers, have been designed with the idea of creating a simplified and universal
      inducible system to facilitate the generation of conditional transgenic, knock
      out, and knock-in animals.

PMID- 15488240
TI  - High capacity and low cost detection of prion protein gene variant alleles by
      denaturing HPLC.
AB  - Mutations in the human prion protein gene (PRNP) are responsible for hereditary
      diseases called transmissible spongiform encephalopathies (TSE) and a polymorphic
      site at codon 129 determines sensitivity to infectious forms of these maladies.
      More recently, codon 129 has been related to cognition performance in the
      elderly, in Alzheimer disease (AD) and in Down syndrome. Furthermore, a rare
      polymorphism at codon 171 was described in 23% of patients with mesial temporal
      lobe epilepsy related to hippocampal sclerosis (MTLE-HS), the most common form of
      surgically remediable epileptic syndrome. Thus, a method that permits fast and
      efficient screening of PRNP mutations and polymorphisms in patients, in high risk
      populations, and in family members is desirable. In the present study, we
      established the conditions for analysis of the PRNP open reading frame using
      denaturing high-performance liquid chromatography (DHPLC), whereby unpurified PCR
      products were subjected to denaturing and reannealing steps leading to
      heteroduplex formation. We described specific profiles for the PRNP polymorphisms
      at codons 129 (M/V), 117 (A/A silent), 219 (E/K), 171 (N/S), and the octarepeat
      deletion using amplified DNA from 562 samples. The chromatograms for TSE
      associated mutations at codons 102 (P/L), 183 (T/A), and 210 (V/I) were also
      determined. Specificity of the DHPLC profile for each PRNP variant allele was
      confirmed in 100% of the samples by direct and cloned DNA sequencing in addition
      to endonuclease digestion when applicable. Therefore, the present study shows
      that DHPLC is a rapid, highly accurate and efficient technique for the detection
      of PRNP genetic variants.

PMID- 15488241
TI  - Fractal dynamics and synchronization of rhythms in urodynamics of female Wistar
      rats.
AB  - Two phenomena are ubiquitous in physiological signals. First, they have temporal
      fractal structure. Secondly, they are rhythmic but with fluctuations. The fractal
      structure and rhythms can alter from normal to abnormal with disease or injury.
      Here, we demonstrate that a temporal "coherent" fractal structure and
      synchronization of rhythms are two essential features for concerted systemic
      functions in urodynamics of female Wistar rats. We report evidence on the dynamic
      interaction in the micturition reflex of lower urinary tract: the rhythms of
      detrusor of the bladder and external urethral sphincter are synchronized around 7
      Hz and their fractal dimensions as functions of time are temporally "coherent"
      under 1.5 during voiding in order to facilitate the concerted process. On the
      other hand, in the spinal cord injured rats, either the temporal coherent
      structure of fractal or the underlying synchronization of rhythms is impaired,
      weakened, or absent. These results have potential implications in the diagnosis
      of the so-called "dynamical" diseases.

PMID- 15488242
TI  - A robust model of adjuvant-induced chronic unilateral arthritis in two mouse
      strains.
AB  - We have developed a model of unilateral adjuvant-arthritis that is reproducible
      across two mouse strains. DBA/1 and C57BL/6 male mice were injected intra
      articularly into a stifle joint with FCA (5 microg in 5 microl) once per week for
      4 weeks. Measurements of joint diameter and joint histopathology were used to
      monitor the course of the arthritis. Inflammatory hyperalgesia was assessed as
      the pressure causing a limb withdrawal. FCA injection into the mouse stifle joint
      caused a pronounced increase in joint diameter when compared to the contralateral
      limb or vehicle controls. There was also a significant decrease in the pressure
      required to elicit a withdrawal of the injected limb. Histology showed arthritic
      changes, including synovial hypertrophy and polymorphonuclear neutrophil
      infiltration. In established chronic inflammation, seven days of treatment with
      either indomethacin (NSAID) or prednisolone (steroid) caused a significant
      decrease in joint inflammation and associated hyperalgesia. FCA induces a long
      lasting joint inflammation in DBA/1 and C57BL/6 mice, which is restricted to the
      injected joint and exhibits some of the pathology associated with an arthritic
      condition. This model will be useful in examining the effect of joint
      inflammation on nociceptor sensitisation in both normal and transgenic mice.

PMID- 15488243
TI  - A MRI-compatible stereotaxic localizer box enables high-precision stereotaxic
      procedures in pigs.
AB  - We present a nonmagnetic Plexiglas stereotaxic localizer box that can be fitted
      directly to the pig skull by aluminum screws, allowing stereotaxic MRI or
      ventriculography and subsequent high-precision stereotaxic procedures. The
      localizer box was used to target the subthalamic nucleus (STN) bilaterally in
      five female Gottingen minipigs. Stereotaxic markers were inserted in the pig
      skull, the head fixated in the localizer box by aluminum screws inserted
      bilaterally in the zygoma bone with the hard palate locked on a horizontal palate
      holder. MRI was obtained on a 3T-MR-imager revealing the relation between the
      inserted markers and the estimated STN-position, and thus the target coordinates.
      After the MRI, a stereotaxic frame with attached micromanipulator was locked on
      to the localizer box converting it into a stereotaxic device. The stereotaxic
      markers were exposed and used as starting point for the stereotaxic procedure,
      whereby a microelectrode for electrolytic lesioning was inserted in the STN.
      Postmortem histological analysis revealed 70% correct STN-targeting. The average
      distance from the lesion center to the STN center was 1.2 mm with a S.D. of 1.1
      mm. The most displaced lesion being 3.6 mm from the STN center. We conclude that
      the described localizer box secure firm head fixation, allowing stereotaxic MRI
      and subsequent conversion into a stereotaxic device for high-precision
      stereotaxic procedures.

PMID- 15488244
TI  - Quantification of NGF-dependent neuronal differentiation of PC-12 cells by means
      of neurofilament-L mRNA expression and neuronal outgrowth.
AB  - We demonstrate that the degree of neuronal development of PC-12 cell
      differentiation can be quantified by the expression of neurofilament-L (NF-L)
      mRNA, when an optimal concentration of NGF (50 ng/ml) is used. During the first 7
      days of NGF treatment, the relative amount of NF-L mRNA was found to increase
      continuously and to correlate with the outgrowth of neurites in a statistically
      significant way. Thus, mRNA expression is, under these conditions, a suitable
      means for reliably monitoring the differentiation of PC-12 cells as early as
      after 3 days of NGF treatment. The results obtained with 5 ng/ml NGF differ from
      those with 50 ng/ml: during the first 3 days of NGF treatment, neuronal outgrowth
      was less than with 50 ng/ml, although the NF-L mRNA levels did not depend
      significantly on NGF concentration. Beyond day 3, NF-L mRNA levels did not
      increase further at 5 ng/ml as opposed to 50 ng/ml NGF. These differences point
      to different signal transduction processes involved in neuronal differentiation
      at high and low NGF concentration. Expression of NF-L protein in response to NGF
      treatment was also demonstrated. In summary, our results stress that stable and
      sustained differentiation of PC-12 cells can only be achieved with 50 ng/ml NGF.

PMID- 15488245
TI  - Do antipsychotics ameliorate or exacerbate Obsessive Compulsive Disorder
      symptoms? A systematic review.
AB  - BACKGROUND: Paradoxically, some reports in the literature support the use of
      antipsychotics in the treatment of Obsessive Compulsive Disorder (OCD), while
      other reports suggest that antipsychotics can exacerbate OCD symptoms. To date,
      there is no published systematic review of the relationship between OCD symptoms
      and antipsychotic drugs. METHODS: A Medline and PsychInfo search (1980-2003) was
      conducted to collect published reports of the interactions between antipsychotics
      and OCD symptoms. RESULTS: In the treatment of refractory OCD, case series, open
      label trials and placebo-controlled trials were found suggesting efficacy of
      antipsychotic augmentation to ongoing antidepressant treatment. In the placebo
      controlled trials with haloperidol, risperidone, olanzapine, and quetiapine, a
      significantly higher response rate (46-71%) was found for the antipsychotic
      groups, compared to no response for the placebo groups. Reports of exacerbation
      of OCD symptoms with the use of atypical antipsychotics were limited to
      individuals with a primary psychotic disorder. LIMITATIONS: Definition of
      response in most of these treatment studies was based on a modest reduction of
      OCD symptoms, and no studies were available on long-term efficacy. There were
      also no published reports that systematically evaluated the incidence of OCD
      symptoms associated with atypical antipsychotics. CONCLUSIONS: All antipsychotics
      mentioned above had short-term controlled evidence to support their use as
      augmenting agents in the treatment of refractory OCD. The suggested management of
      OCD induction/exacerbation due to atypical antipsychotics is to increase the dose
      of the atypical antipsychotic and/or add a selective serotonin reuptake
      inhibitor.

PMID- 15488246
TI  - The phenomenology and treatment of interferon-induced depression.
AB  - Interferon (IFN)-alpha, IFN-beta, and IFN-gamma are currently available for the
      treatment of malignancies, viral infections (e.g., hepatitis C virus), multiple
      sclerosis (MS), and skin conditions. In addition to their therapeutic effects,
      IFNs commonly cause various side effects. Most common among the side effects of
      IFN are "flu-like" symptoms such as chills, fever, and muscle soreness. However,
      IFN can also cause significant neuropsychiatric side effects, particularly
      symptoms of depression. A literature search was conducted in order to summarize
      current information on (1) the frequency, characteristics, and risk factors of
      IFN-induced depression, (2) possible biochemical mechanisms associated with IFN
      induced depression, and (3) the treatment strategies for IFN-induced depression.
      Review of the literature suggests that symptoms of depression induced by IFN
      therapy, in particular IFN-alpha therapy, are common and can limit the treatment
      utility, often necessitating discontinuation of IFN therapy or the use of
      psychopharmacologic agents. Depression is also a suspected side effect of therapy
      with IFN-beta and IFN-gamma; however, the association has not been as
      convincingly confirmed. Importantly, IFNs affect neurochemical pathways
      putatively involved in the etiology of depression. While these depressive side
      effects usually resolve after the completion of IFN therapy, they can persist or
      reappear with dose escalations. It is recommended that health care providers,
      patients and their families be informed about the potential risk of the
      psychiatric disturbances that can occur with IFN-alpha therapy. Screening and
      monitoring, ideally using symptom rating scales for depression, and early
      antidepressant treatment intervention appear necessary to optimize IFN therapy
      for the majority of patients.

PMID- 15488247
TI  - Decreased activation of the anterior cingulate in bipolar patients: an fMRI
      study.
AB  - BACKGROUND: Previous neuroimaging investigations of patients with bipolar
      disorder have reported abnormalities of the frontal subcortical network. The role
      of the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex
      (DLPFC) in bipolar disorder are not clear, although both regions have been shown
      to be components of a neural network which plays a critical role in the
      completion of tasks requiring self-monitoring and inhibition, functions often
      noted to be altered in bipolar patients. fMRI studies have helped clarify the
      role of specific subdivisions of the ACC and the DLPFC during the performance of
      cognitive challenges, including the Stroop color word test. To date, studies that
      have examined ACC function in bipolar patients have not differentiated subregions
      within this area, nor have they examined changes in these subregions in relation
      with DLPFC activation. METHODS: To help clarify the specific roles of these
      regions in bipolar patients, we examined stable patients and control subjects
      during performance of the Stroop test using BOLD fMRI techniques. We hypothesized
      that bipolar patients would demonstrate reduced activation of two subdivisions of
      the ACC (AAA and VOA), as well as altered activation of the DLPFC, during the
      interference condition. RESULTS: Results indicate that relative to controls,
      bipolar patients demonstrated significantly reduced signal intensity within the
      right AAA subdivision (p=0.011), which accompanied an increase in the DLPFC
      (p=0.049) during the task. LIMITATIONS: The study sample was somewhat small (11
      patients, 10 controls) which limits the generalizability of the study findings,
      however, the patient sample consisted of well-diagnosed, stable, chronic
      individuals with bipolar disorder and the sample size provided enough power to
      detect between-group differences. CONCLUSIONS: These findings suggest
      differential processing strategies of bipolar patients and support the theory of
      altered frontal systems in these patients during the performance of cognitive
      tasks.

PMID- 15488248
TI  - Increased sensitivity to error during decision-making in bipolar disorder
      patients with acute mania.
AB  - BACKGROUND: Decision-making is a complex and important function for daily life
      that can be assessed quantitatively using a simple two-choice prediction task.
      Bipolar disorder (BD) patients are thought to show altered responsivity to
      positive and negative feedback. In this study we examined whether BD patients
      with psychotic mania show altered patterns of decision-making as a function of
      the frequency of incorrect predictions or error rate. METHODS: Fourteen adult DSM
      IV-diagnosed BD patients with psychotic mania and 14 normal comparison subjects
      (NC) were tested with a two-choice prediction task using three error rate
      conditions (20%, 50%, or 80%). RESULTS: BD patients showed an increased
      sensitivity to error rate changes and switched more frequently at high error
      rates than NC subjects. In comparison, there were no differences between BD and
      NC subjects on the degree to which the response or stimulus during a previous
      trial predicts the current response. CONCLUSIONS: Decision-making in BD patients
      with psychotic mania appears to be highly sensitive to high error rates.
      Moreover, the patterns of responses appear distinct from what has been previously
      observed in acutely and chronically ill schizophrenia patients. The results of
      this study are informative as to the effects of errors on decision-making
      strategies in psychotic BD manic patients.

PMID- 15488249
TI  - Does referral bias impact findings in high-risk offspring for anxiety disorders?
      A controlled study of high-risk children of non-referred parents with panic
      disorder/agoraphobia and major depression.
AB  - BACKGROUND: Previous findings in referred samples documented significant
      diagnostic specificity in patterns of transmission between parents with panic
      disorder (PD) and parents with major depression (MD) and their offspring. This
      study evaluated whether these patterns of transmission between parents and high
      risk offspring are moderated by referral bias. METHODS: Parental PD/agoraphobia
      (AG) and parental MD were used to predict rates of offspring psychiatric
      disorders and functional outcomes using data from an opportunistic sample of
      parents (n = 991) and offspring (n = 734) ascertained from case-control family
      genetic studies of youth with and without attention-deficit hyperactivity
      disorder. Subjects were comprehensively assessed with structured diagnostic
      interview methodology to evaluate psychiatric disorders in parents and offspring.
      RESULTS: Parental PD/AG increased the risk for anxiety disorders in offspring,
      independently of parental MD while parental MD increased the risk for mood and
      disruptive behavior disorders in offspring, independently of parental PD/AG.
      Parental psychopathology was also associated with functional impairment in
      offspring. LIMITATIONS: The use of a sample ascertained by ADHD and control
      probands, and parent psychiatric diagnostic reports for children under 12.
      CONCLUSIONS: These results extend to non-referred samples previous findings from
      referred samples documenting diagnostic specificity in the familial transmission
      of PD/AG and MD from parents to offspring, suggesting that these patterns of
      transmission are not due to referral bias. These results could inform and enhance
      community programs aimed at screening for and treating pediatric psychopathology.

PMID- 15488250
TI  - Adverse childhood experiences and the risk of depressive disorders in adulthood.
AB  - BACKGROUND: Research examining the association between childhood abuse and
      depressive disorders has frequently assessed abuse categorically, thus not
      permitting discernment of the cumulative impact of multiple types of abuse. As
      previous research has documented that adverse childhood experiences (ACEs) are
      highly interrelated, we examined the association between the number of such
      experiences (ACE score) and the risk of depressive disorders. METHODS:
      Retrospective cohort study of 9460 adult health maintenance organization members
      in a primary care clinic in San Diego, CA who completed a survey addressing a
      variety of health-related concerns, which included standardized assessments of
      lifetime and recent depressive disorders, childhood abuse and household
      dysfunction. RESULTS: Lifetime prevalence of depressive disorders was 23%.
      Childhood emotional abuse increased risk for lifetime depressive disorders, with
      adjusted odds ratios (ORs) of 2.7 [95% confidence interval (CI), 2.3-3.2] in
      women and 2.5 (95% CI, 1.9-3.2) in men. We found a strong, dose-response
      relationship between the ACE score and the probability of lifetime and recent
      depressive disorders (P<0.0001). This relationship was attenuated slightly when a
      history of growing up with a mentally ill household member was included in the
      model, but remained significant (P<0.001). CONCLUSIONS: The number of ACEs has a
      graded relationship to both lifetime and recent depressive disorders. These
      results suggest that exposure to ACEs is associated with increased risk of
      depressive disorders up to decades after their occurrence. Early recognition of
      childhood abuse and appropriate intervention may thus play an important role in
      the prevention of depressive disorders throughout the life span.

PMID- 15488251
TI  - Self-criticism and social phobia in the US national comorbidity survey.
AB  - BACKGROUND: This study sought to extend findings from a preliminary clinical
      investigation [J. Affect. Disord. 57 (2000) 223] by examining relations between
      the personality dimension of self-criticism and diagnostic prevalence of social
      phobia in a large nationally representative sample. METHODS: Participants were
      from the national comorbidity survey Part II [n=5877; Arch. Gen. Psychiatry 51
      (1994) 8]. Psychiatric diagnoses were made using a modified version of the
      composite international psychiatric interview. Personality dimensions and
      distress were assessed using brief self-report measures with strong psychometric
      properties. RESULTS: Self-criticism was elevated in NCS respondents with a
      diagnosis of social phobia, even in cases of only past history of social phobia
      (i.e. >1 year ago), compared to individuals with no psychiatric disorder. The
      highest levels of self-criticism were reported by people with the complex subtype
      of social phobia, both with and without comorbid major depression. These levels
      were significantly greater compared to those observed in another anxiety disorder
      (panic disorder), the pure speaking subtype of social phobia, and cases of major
      depression alone. In a regression analysis that controlled for current emotional
      distress, the broad personality trait of neuroticism, and lifetime histories of
      mood, anxiety, and substance use disorders, self-criticism remained significantly
      associated with lifetime prevalence of social phobia. LIMITATIONS: The cross
      sectional design of the study does not permit causal inferences. CONCLUSIONS:
      Findings from this general population mental health survey demonstrated that self
      criticism is robustly associated with social phobia. It may represent an
      important core psychological process in the complex subtype of this anxiety
      disorder.

PMID- 15488252
TI  - A population study of the association between sexual function, sexual
      satisfaction and depressive symptoms in men.
AB  - BACKGROUND: Depression and erectile dysfunction (ED) have a complex and bi
      directional relationship. We examined the relationships between erectile
      dysfunction and depressive symptoms or diagnosed depression, sexual activity and
      sexual satisfaction. METHODS: A population survey of men aged 40-70 years was
      carried out in Brazil, Italy, Japan and Malaysia in 1997-1998. A questionnaire
      was used to collect life style, sexual behaviors and medical data. Depressive
      symptoms were assessed using the Center for Epidemiologic Studies Depression
      Scale. ED was classified as moderate or complete if the men reported they were
      "sometimes" or "never" able to achieve and maintain an erection satisfactory for
      sexual intercourse. Only men with a sexual partner and not taking psychoactive
      drugs were considered. RESULTS: Diagnosed depression was reported by 2.0% of the
      men, depressive symptoms by 21.0%. The prevalence of moderate or complete ED was
      17.8%. Sexual satisfaction related to the frequency of sexual intercourse and
      inversely related to depressive symptoms. Depressive symptoms were positively
      associated with being single (odds ratio [OR] 1.7), widowed, separated or
      divorced (OR 2.2), moderate or complete ED (1.8), heart disease (1.6) and smoking
      (1.6), and negatively associated with age, physical activity and frequency of
      sexual intercourse. LIMITATIONS: Cross-sectional studies cannot establish a
      temporal cause-effect relationship. However, the confirmation of known
      associations reassures about the validity of the original findings. CONCLUSIONS:
      The findings suggest that depressive symptoms are linked to ED by the mediation
      of decreased sexual activity and the dissatisfaction generated by the inability
      to have a healthy sexual life.

PMID- 15488253
TI  - The influence of major depression and its treatment on heart rate variability and
      pupillary light reflex parameters.
AB  - BACKGROUND: The link between depression and autonomic dysfunction has attracted
      more attention since epidemiological studies have revealed that depressed
      patients have an augmented risk of cardiovascular morbidity and mortality. Former
      studies of autonomic dysfunction in major depression have shown inconclusive
      results. AIMS: To further elucidate the effect of depression and medication on
      autonomic function, 18 patients and 18 matched control subjects were
      comprehensively assessed once medicated and once non-medicated as well as after
      full clinical recovery. METHODS: Cardiac autonomic function was evaluated by
      measuring heart rate variability (HRV) parameters, and central autonomic tone was
      investigated by obtaining parameters of the pupillary light reflex (PLR).
      RESULTS: Acutely depressed patients who had not taken antidepressant medication
      for 8 weeks prior to the investigation differed significantly neither in heart
      rate parameters nor in parameters of the PLR from their controls. However, after
      2 days of antidepressant treatment (SSRI and NaSSRI), parameters of heart rate
      analysis and PLR (except relative amplitude) changed significantly and remained
      significantly different after clinical recovery. LIMITATIONS: The study needs to
      be repeated using larger patient groups. Long-term studies are absolutely
      essential. CONCLUSION: The state of depression did not influence autonomic
      parameters significantly. In fact, treatment influenced autonomic function far
      more than the disease itself. Other branches of the autonomic nervous system
      (ANS), as well as new techniques should be applied to elucidate whether small
      changes in autonomic function exist. This might clarify whether disease or
      treatment might influence cardiac mortality in depression.

PMID- 15488254
TI  - Evidence for continuing neuropsychological impairments in depression.
AB  - BACKGROUND: Neuropsychological deficits have been reported in patients with major
      depressive disorder (MDD) during an acute episode of MDD. Little is known whether
      these abnormalities persist when patients are remitted. The purpose of the
      present study was to describe the neuropsychological functioning of fully
      remitted, unmedicated patients with a history of MDD by focusing on tasks related
      to prefrontal cortex functioning. METHODS: Twenty-eight young to middle-aged,
      unmedicated, fully remitted patients with MDD were compared to 23 healthy control
      subjects on tasks from the Cambridge Automated Neuropsychological Test Battery
      (CANTAB) and the California Verbal Learning Test (CVLT). RESULTS: Patients with
      remitted MDD relative to controls were impaired on tasks of rapid visual
      information processing (RVIP), psychomotor performance and spatial working memory
      (SWM). After correction for residual depressive symptoms, deficits in sustained
      attention remained significant. LIMITATIONS: CANTAB tasks are not equated for
      difficulty, and difficulty differences between the CANTAB tasks and the CVLT are
      not known. CONCLUSIONS: These findings suggest deficits in sustained attention as
      vulnerability marker for MDD. The functional importance of this finding and the
      neuronal networks involved remain to be elucidated.

PMID- 15488255
TI  - The problem of diagnosing major depression in elderly primary care patients.
AB  - BACKGROUND: To clarify the problem of diagnosing major depression in elderly
      primary care patients, we studied the nuances of diagnostic classification by
      general practitioners (GPs) and the relationship between sociodemographic and
      clinical factors and an accurate diagnosis of depression. METHODS: As part of a
      national survey of general practice a standardised psychiatric interview (CIDI)
      was performed in 237 subjects > or =55 years screened for the presence of
      psychopathology. Fifty-five patients were found to suffer from a major depressive
      disorder in the last 12 months. In these patients, GPs registered during 1 year
      all contact diagnoses and prescriptions of medication. RESULTS: Nearly all
      depressed patients (96.4%) had one or more contacts with their GP during 1 year.
      GPs classified 20.8% of the patients as having a down/depressed feeling or
      depression, while 32.1% as having other psychological problems than depression.
      It was remarkable that an accurate diagnosis by GPs was significantly related to
      higher age in this age group. Regarding the clinical characteristics, there was a
      significantly higher number of prescriptions of antidepressants in the accurately
      diagnosed patients. We found no significant differences in respect to other
      clinical characteristics (e.g. severity and number of symptoms, comorbidity of
      anxiety and somatic disorders). CONCLUSIONS: GPs are aware of the psychological
      problems in half of the elderly patients with major depression, but do not
      explicitly distinguish depressive symptoms from other psychological problems or
      from social problems. Integrated programs may be more promising to improve the
      diagnostic rate than clinical education or guideline implementation alone.

PMID- 15488256
TI  - Verbal memory and aspects of attentional control in children and adolescents with
      anxiety disorders or depressive disorders.
AB  - BACKGROUND: The aim was to examine basic performance on attention and memory
      tasks in treatment-naive children and adolescents with anxiety disorder or
      depressive disorder and in healthy subjects under drug-free conditions. METHODS:
      Basic neurocognitive performance on attention and verbal memory tasks was
      examined in children and adolescents with emotional disorders, between 6 and 17
      years of age. A total of 34 children with an anxiety disorder, 31 children with a
      depressive disorder, and 33 healthy controls were assessed with a comprehensive
      neuropsychological test battery. All children were treatment-naive at the time of
      testing. Five different computerised attention tasks and the Rey Auditory-Verbal
      Learning Test were administered. RESULTS: A significant effect of diagnosis was
      found for verbal memory but not for attention. LIMITATIONS: The large age range
      and inclusion of different diagnoses resulted in rather inhomogeneous groups.
      CONCLUSION: The present study provided evidence for an undisturbed attentional
      performance in both patient groups and a dissociation in memory functioning
      between anxious and depressed children. Memory impairment was found to be
      specifically associated with childhood depression.

PMID- 15488257
TI  - Base rates for panic and depression according to the Brief Patient Health
      Questionnaire: a population-based study.
AB  - BACKGROUND: Recently published studies analyzing sensitivity and specificity
      scores have demonstrated that the brief version of the Patient Health
      Questionnaire (PHQ [J. Am. Med. Assoc. 282 (1999) 1734]) is a useful tool for the
      detection of panic disorder and depression. METHODS: We aimed to get normative
      data for the brief PHQ in a representative population-based sample.
      Sociodemographic data and PHQ data from 2066 subjects were included. RESULTS:
      Base rates for PHQ criteria of major depression were 3.8% with the typical 1:2
      ratio between males and females (frequency of minor depressive forms: 9.2%).
      Normative data for the depression total scores were reported. Marital status,
      education and family income were significantly associated with depression, even
      after controlling for age and sex. For panic disorder, base rates were 1.8%; age,
      gender, and marital status were significant predictors. Frequency for panic
      attacks as a less restrictively defined version were 4.5%. CONCLUSIONS: The
      normative data provide a framework for the interpretation of depression and panic
      scores of the PHQ.

PMID- 15488259
TI  - Delayed vasodilatory response to methylnicotinate in patients with unipolar
      depressive disorder.
AB  - BACKGROUND: Recent evidence has suggested an important role for lipids in the
      etiology and treatment of depression. Methylnicotinate-induced vasodilation can
      be used to investigate lipid-dependent signalling mechanisms involving the
      phospholipase A2 (PLA2)/cyclooxygenase pathway, an important signalling system
      involved in the action of several neurotransmitters including serotonin. To
      investigate whether abnormalities in this signalling system may occur in
      depressive illness, we undertook a study of methylnicotinate response in unipolar
      depression (UD). METHODS: Methylnicotinate was applied to the forearm of 20
      patients with depression and 38 age and sex-matched healthy volunteers (HV). The
      resulting erythema was assessed over a 15-min period. RESULTS: Methylnicotinate
      induced erythema was reduced in subjects with depression compared to HV at 5 min
      after application, it returned to normal after 15 min. Thus, although the maximal
      response to methylnicotinate appears normal, patients with UD exhibit an
      apparently delayed response. LIMITATIONS: The major limitation is that all
      unipolar patients were medicated at the time of testing. CONCLUSIONS: Our results
      support the hypothesis that UD may be associated with abnormalities in lipid
      associated signalling systems, and may provide insight into how lipid intake may
      modulate depressive symptoms.

PMID- 15488258
TI  - Personality disorder, depression and functioning: results from the ODIN study.
AB  - BACKGROUND: There is little information of the prevalence of personality disorder
      (PD) in those with depressive disorder in community samples; neither is there any
      data on the impact of PD on service utilisation or outcome in this setting.
      METHODS: A two stage screening study to identify cases of depressive disorder
      using SCAN in five European countries. Personality assessed 6 months after the
      diagnostic interview. Follow-up for 1 year using symptom and social function
      measures. RESULTS: Personality disorder is present in 22% of a community sample
      with depressive disorders but the range varied from 13.7% to 33.3% across
      countries. Cluster C formed 43% of the total. Long-term psychotropic drug use was
      more common in the PD group even after depression was controlled. Those with PD
      had higher symptom scores at the outset and, although the PD group was more
      likely to be cases at follow-up, this disappeared when the depression score was
      co-varied. Only initial social function predicted outcome at 6 and 12 months.
      LIMITATIONS: The use of a non-treatment seeking population may limit the
      application of the findings to clinical populations. CONCLUSIONS: PD is common
      even in a non-treatment seeking population with depressive disorder. It impacts
      upon outcome at 6 and 12 months but this is related to the initial severity of
      depressed mood. Social function is the only independent predictor of outcome and
      should be assessed separately.

PMID- 15488260
TI  - Is the type of remission after a major depressive episode an important risk
      factor to relapses in a 4-year follow up?
AB  - BACKGROUND: Rates of relapse and predictive relapse factors were studied over
      more than 4 years in a sample of Spanish outpatients with DSM-III-R criteria for
      unipolar major depressive episode. METHODS: A final sample of 139 outpatient was
      followed monthly in a naturalistic study. The Structured Clinical Interview for
      DSM-III-R was used. Phases of evolution were recorded using the Hamilton
      Depression Rating Scale, applying the Frank criteria. Survival analysis, Kaplan
      Meier product limit and proportional hazards models were used. RESULTS: A higher
      rate of relapses was observed in the partial remission group (91.4%) compared to
      the complete remission one (51.3%). The four factors with predictive relapse
      value were: "partial remission versus complete remission", "the intensity of
      clinical symptoms", "the age" and "the number of previous depressive episodes".
      The existence of partial remission was the most powerful predictive factor.
      LIMITATIONS: The decreasing sample size during the follow-up and the difficulty
      in warranting the treatment compliance. CONCLUSIONS: At medium term, relapse
      rates for a major depressive episode are high. Partial remission after a
      depressive episode seems to be an important predictive factor for relapses in a 4
      year follow-up. CLINICAL RELEVANCE: Not reaching complete remission is a strong
      risk factor for relapses in a 4-year follow up study.

PMID- 15488261
TI  - Prevalence rates and psychosocial characteristics associated with depression in
      pregnancy and postpartum in Maltese women.
AB  - BACKGROUND: Investigators have commented on the apparent high prevalence of
      psychiatric symptoms in pregnancy. In Malta there is lack of epidemiological data
      and therefore, the prevalence of depression during pregnancy and at 8 weeks
      postpartum among a community sample of Maltese women was carried out. METHOD: A
      random sample of 239 pregnant women were interviewed at booking using a detailed
      sociodemographic history, the revised version of the clinical interview schedule
      (CIS-R) and Maltese translation of the Edinburgh postnatal depression scale
      (EPDS). The CIS-R was again administered over the phone at 36 weeks and the EPDS
      sent by post. At 8 weeks postpartum, the CIS-R, modified version of the social
      maladjustment schedule and the EPDS were again administered to 95.8% of women.
      RESULTS: The point prevalence of depression meeting ICD-10 research criteria was
      15.5% at booking, 11.1% in the third trimester and 8.7% postpartum of which only
      3.9% had an onset since delivery. CONCLUSIONS: The low rate of new onset
      postpartum depression compared with other studies in our sample may be
      attributable to the social support available to women living in a cohesive
      Catholic island community. LIMITATION: The follow-up was limited to 8 weeks
      postpartum. No control group was used to compare the prevalence of depression in
      women who did not recently have a baby.

PMID- 15488262
TI  - Safety of Hypericum extract in mildly to moderately depressed outpatients: a
      review based on data from three randomized, placebo-controlled trials.
AB  - RATIONALE: Hypericum extracts have been regarded as antidepressant drugs without
      specific side effects by patients, medical professionals and researchers alike.
      Recently there has been discussion about potential interactions between St.
      John's wort and other drugs. OBJECTIVES: To investigate the tolerability of
      Hypericum extract by comparing adverse event rates observed during clinical
      trials with the herbal drug to those observed under placebo and synthetic
      antidepressants. METHODS: A data review was performed based on the original data
      of three double-blind, randomised multicenter trials, during which 594 out
      patients suffering from mild to moderate depression according to DSM-IV criteria
      received 3 x 300 mg/day Hypericum extract (WS 5570, WS 5572, WS 5573) or placebo
      over a double-blind treatment period of 6 weeks. For the polled data from the
      three trials, the risk ratios and risk differences versus placebo for single and
      grouped adverse events were determined along with their 95% confidence intervals.
      The data were inspected for relevant differences between Hypericum extract and
      placebo and were compared to trials involving the administration of several
      synthetic antidepressants. RESULTS: For the polled data of the three trials, the
      percentage of patients with any adverse events under Hypericum extract exposition
      was comparable to placebo. The drug was also found to be devoid of effects of
      sedation, anticholinergic reactions, gastrointestinal disturbances and sexual
      dysfunction often found in patients treated with tricyclic antidepressants or
      selective serotonin reuptake inhibitors. CONCLUSION: The analysis did not reveal
      any specific effects of Hypericum extract.

PMID- 15488263
TI  - Cytokine production in bipolar affective disorder patients under lithium
      treatment.
AB  - BACKGROUND: Our knowledge concerning immune functioning in bipolar affective
      disorder (BAD) is limited, while lithium's immunomodulatory effects seem multiple
      and conflicting. Our aim was to evaluate cytokine production and lithium's effect
      on it in BAD patients, using ELISPOT technique as a sensitive tool. METHODS:
      Cytokine (IL-2, IL-6, IL-10 and IFN-gamma) production from isolated peripheral
      blood lymphocytes (PBLs) was evaluated (ELISPOT technique) in 40 euthymic BAD
      patients under chronic lithium treatment, in 20 healthy volunteers, and in 10
      never medicated BAD patients before and after the introduction of lithium
      therapy. In all cases, cytokine plasma levels were also measured using ELISA.
      RESULTS: BAD patients under chronic lithium treatment had significantly lower
      numbers of IL-2, IL-6, IL-10 and IFN-gamma secreting cells compared to healthy
      volunteers. The number of cytokine secreting cells decreased in never medicated
      patients after 3 months of lithium treatment. In vitro stimulation of PBLs with
      lithium did not affect the number of cytokine secreting cells either in the
      patients or in the healthy volunteers. CONCLUSIONS: The significantly lower
      number of PBLs producing cytokines (IL-2, IL-6, IL-10 and IFN-gamma) in euthymic
      BAD patients under chronic lithium treatment result from the long-term (over 3
      months) lithium administration. In vitro stimulation of PBLs with lithium did not
      change the number of cytokine producing cells. Our findings may be useful in
      elucidating possible downregulatory effects of lithium in humans.

PMID- 15488264
TI  - An exploration of comorbid depression among female victims of intimate partner
      violence with posttraumatic stress disorder.
AB  - BACKGROUND AND METHODS: Factors contributing to posttraumatic stress disorder
      (PTSD) and comorbid major depression (MDD) were investigated among female victims
      of intimate partner violence (IPV). RESULTS: High levels of PTSD (75% of the
      sample) and MDD (54% of the sample) were observed. Individuals with both PTSD and
      MDD reported significantly greater levels of PTSD and depression symptoms than
      individuals with either PTSD alone or without major psychopathology. Individuals
      with comorbid PTSD and MDD had more maladaptive depressogenic cognitive styles
      than individuals without PTSD. The three groups were comparable in terms of pre
      abuse mental health, childhood trauma history, and relationship violence
      variables and injuries. Maladaptive schemas did not contribute to the
      identification of comorbidity caseness, whereas PTSD severity and prior trauma
      did. Psychological aggression by an abuser and PTSD severity accounted for 52% of
      the variance in depressive symptoms. LIMITATIONS: Cross-sectional design and lack
      of trauma-specific cognitive measures. CONCLUSIONS: The findings confirm that
      comorbid PTSD and MDD is common among IPV victims. The mechanisms that contribute
      to comorbid depression, however, are unclear, and prospective studies are
      necessary to delineate the roles that psychological abuse, PTSD severity and
      prior trauma experiences may have in the development of depression following IPV.

PMID- 15488265
TI  - PET brain imaging with [11C](+)McN5652 shows increased serotonin transporter
      availability in major depression.
AB  - BACKGROUND: Alterations in the brain serotonin (5-HT) system have been found in
      patients with depression. We used the selective 5-HT transporter site ligand
      [11C](+)McN5652 and positron emission tomography (PET) to examine the hypothesis
      that alterations in 5-HT transporter levels may be present in selected regions of
      the brain in depressed patients. METHODS: Four drug free depressed patients and
      four healthy control subjects were studied using [11C](+)McN5652 and PET. The
      distribution volume (DV) ratio of the PET ligand in selected regions of interest
      (ROIs) compared to cerebellum were calculated for the ROIs. RESULTS: Patients
      showed significantly larger DV ratios in the left frontal cortex (P=0.013) and
      right cingulate cortex (P=0.043) compared to control subjects. LIMITATION: The
      sample size was modest with gender differences between the subject groups. The
      PET agent, [11C](+)McN5652, may have a lower binding affinity for the 5-HT
      transporter in the cortical regions compared to other brain regions. CONCLUSION:
      These findings suggest that 5-HT transporter sites may be increased in the
      frontal and cingulate cortices of depressed patients. These alterations in 5-HT
      transporter sites may be of pathophysiologic significance in the etiology of
      depression and its treatment.

PMID- 15488266
TI  - Efficacy of E2-sub-unit marker and C-strain vaccines in reducing horizontal
      transmission of classical swine fever virus in weaner pigs.
AB  - At present, two types of vaccines against classical swine fever (CSF) virus are
      commercially available: E2 sub-unit marker vaccines and the conventional
      attenuated live C-strain vaccines. To evaluate the reduction of the horizontal
      virus transmission, three comparable experiments were carried out in which groups
      of weaner pigs (vaccinated with a marker vaccine or a C-strain vaccine) were
      challenged with CSF virus at 0, 7, and 14 days post-vaccination (dpv). Virus
      transmission was prevented totally when the challenge occurred at 14 dpv with an
      E2-marker vaccine (0/12 contact pigs positive in virus isolation (VI); R = 0 (0;
      1.5)). At 7 dpv, transmission was reduced slightly (5/12 contact pigs positive in
      VI; R = 1.0 (0.3; 3.0)), whereas at 0dpv, vaccination had no effect on
      transmission (10/12 contact pigs positive in VI; R = 2.9 (1.5; 10.8)). In the C
      strain-vaccinated pigs, no virus transmission was detected even when the
      challenge was performed at the same day as the vaccination (0/12 contact pigs
      positive in VI; R = 0 (0; 1.5)).

PMID- 15488267
TI  - Effects of altitude, distance and waves of movement on the dispersal in Australia
      of the arbovirus vector, Culicoides brevitarsis Kieffer (Diptera:
      Ceratopogonidae).
AB  - The dispersal of the biting midge and arbovirus vector Culicoides brevitarsis in
      the Bellinger, Macleay and Hastings river valleys and up the escarpment of the
      great dividing range (GDR) of mid-northern coastal New South Wales, Australia,
      from 1995 to 2003 was studied. The midge moved up these valleys from the endemic
      coastal plain in at least two waves between October and May, and both waves were
      modelled. Dispersal time can be explained by direct distance from the coast and
      the altitude of the sites. Dispersal times due to distance were similar at 18.2
      +/- 2.2 (S.D.) and 15.9 +/- 2.6 weeks per 100 km for first- and second
      occurrences at fixed altitude. Time of the first wave was extended 0.48 +/- 0.22
      weeks for every 100-m rise in altitude and the second by 1.14 +/- 0.24 weeks for
      every 100-m rise for a set distance. Although C. brevitarsis can move up the
      escarpment of the GDR (and possibly transmit virus), vector dispersal, survival
      and establishment at and beyond the top of the range are limited. A third model
      showed that previously described slower movement of C. brevitarsis up the more
      southerly Hunter valley relative to movements down the coastal plain also was
      related to increasing altitude.

PMID- 15488268
TI  - Estimating the number of undetected multi-resistant Salmonella Typhimurium DT104
      infected pig herds in Denmark.
AB  - In Denmark, the detection of multi-resistant Salmonella Typhimurium DT104
      (MRDT104)-infected pig herds relies on the national Salmonella surveillance
      programme at the farm and slaughterhouse levels of production. With the
      surveillance sampling protocol and the diagnostic methods currently used, some
      herds might remain undetected. The number of undetected Danish pig herds infected
      with MRDT104 in the period 1 August 2001-31 July 2002 was estimated and compared
      with the number of culture-confirmed detected herds. A flow chart was constructed
      to illustrate where infected herds will go undetected in the surveillance system
      and Monte Carlo simulation was used to model the actual number of pig herds
      infected with MRDT1104. We estimated that 52 (90% CI [28, 178]) finisher herds
      were infected with MRDT104 compared to 23 (44%) detected. Among sow herds with
      production of weaners or growers, we estimated that 38 (90% CI [23, 74]) were
      infected with MRDT104 compared to 7 (18%) actually detected. Among breeder and
      multiplier herds, we estimated that five (90% CI [3, 8]) herds were infected with
      MRDT104 compared to three (60%) detected. In total, we estimated that 102 pig
      herds were infected with MRDT104 from 1 August 2001 till 31 July 2002 (90% CI
      [63, 228]). In comparison, 33 (32%) infected herds were detected in this period.
      The predicted proportion of undetected herds varied considerably with herd type.
      We infer that the proportion of detected MRDT104 infected herds depended on the
      intensity of the combined serological and bacteriological testing.

PMID- 15488269
TI  - A practical approach to calculate sample size for herd prevalence surveys.
AB  - When designing a herd-level prevalence study that will use an imperfect
      diagnostic test, it is necessary to consider the test sensitivity and
      specificity. A new approach was developed to take into account the imperfections
      of the test. We present an adapted formula that, when combined with an existing
      piece of software, allows improved planning. Bovine paratuberculosis is included
      as an example infection because it originally stimulated the work. Examples are
      provided of the trade-off between the benefit (low number of herds) and the
      disadvantage (large number of animals per herd and exclusion of small herds) that
      are associated with achieving high herd-level sensitivity and specificity. We
      demonstrate the bias in the estimate of prevalence and the underestimate of the
      confidence range that would arise if we did not account for test sensitivity and
      specificity.

PMID- 15488270
TI  - Certification of herds as free of Mycobacterium paratuberculosis infection:
      actual pooled faecal results versus certification model predictions.
AB  - Dutch dairy herds closed for at least 3 years with no history of paratuberculosis
      were recruited for a study on herd-certification. One hundred dairy herds were
      tested for Mycobacterium paratuberculosis at 6-month intervals by pooled faecal
      culture (five individual animal samples per pool) with solid media. Ninety of the
      herds completed 9 herd tests and 10 herds dropped out of the study for reasons
      other than a paratuberculosis diagnosis. Of the 90 herds completing the full
      study, 61% eventually were found to be M. paratuberculosis-infected. The number
      of infected herds detected decreased with each round of testing. Assuming that
      all infected herds had been detected by the ninth herd test, the observed
      percentage of herds that were truly noninfected (P-free) after each round of
      testing was calculated. The observed P-free was compared to the predicted P-free
      based on a previously reported herd-certification model. The P-free predicted by
      the model was significantly different from the observed P-free. When a single
      assumption in the model was changed and a diagnostic sensitivity of 40-50% was
      selected, the predicted P-free closely approximated the observed P-free for the
      90 Dutch dairy herds studied. The critical assumption that was changed for
      Version 2.0 of the model was within-herd infection prevalence for infected but
      test-negative herds after each round of serial testing. Model Version 1.0 had
      assumed a 50% decrease in within-herd prevalence but Version 2.0 assumed a stable
      within-herd prevalence. Culture of pooled faecal samples provides a high
      sensitive, high-specific, low-cost test for herd-certification programs.

PMID- 15488271
TI  - Seroprevalences for ovine enzootic abortion in Switzerland.
AB  - Our aim was to assess the seroprevalence of Chlamydophila (Cd) abortus (Chlamydia
      psittaci serotype 1), denoted ovine enzootic abortion (OEA), in the Swiss sheep
      population. A competitive enzyme-linked immunosorbent assay (cELISA) was adapted
      for the investigation of pooled serum samples (pool approach) and receiver
      operator characteristic (ROC) analysis was applied to define the cut-off of the
      pool approach. At a cut-off value of 30% inhibition, the flock-level pooled
      sensitivity and specificity were 92.9% and 97.6% when compared to classifying the
      flock based on individual-animal samples. Subsequently, sera from 775 randomly
      selected flocks out of 11 cantons of Switzerland were investigated using the pool
      approach. The cantons included in the study represented 72% of the Swiss sheep
      flocks and 76% of Swiss sheep population. Antibodies against Cd. abortus were
      found in almost 19% (144) of the 775 examined sheep flocks. Test prevalences were
      adjusted for the imperfect test characteristics using the Rogan-Gladen estimator
      and Bayesian inference. Seroprevalence was highest (43%) in the canton
      Graubunden. In the remaining 10 cantons the seroprevalence ranged from 2 to 29%.
      The cELISA in combination with testing pooled sera and statistical methods for
      true prevalence estimation provided a good survey tool at lower costs and time
      when compared to other approaches.

PMID- 15488272
TI  - Control of a foot-and-mouth disease epidemic in Argentina.
AB  - A major epidemic of foot-and-mouth disease affected Argentina during 2001. The
      epidemic was controlled by mass-vaccination of the national herd and movement
      restrictions. The median herd disease reproduction ratio (RH) decreased
      significantly from 2.4 (before the epidemic was officially recognized) to 1.2
      during the mass-vaccination campaign and < 1 following the mass-vaccination
      campaign. The largest distance between two outbreaks was similar during (1905 km)
      and after (1890 km) the mass-vaccination. However, after mass-vaccination was
      completed, the proportion of herd outbreaks clustered decreased from 70.4% to
      66.8%, respectively. Although a combination of vaccination and livestock-movement
      restrictions was effective in controlling the epidemic, 112 herd outbreaks
      occurred up to 6 months after the end of the mass-vaccination campaign. Mass
      vaccination and movement restrictions might be an effective strategy to control
      FMD; however, the time taken to end large, national epidemics might be > 1 year.

PMID- 15488273
TI  - Herd demographics correlated with the spatial distribution of a foot-and-mouth
      disease epidemic in Buenos Aires province, Argentina.
AB  - During a recent foot-and-mouth disease epidemic in Argentina, cattle herds
      affected in 2001 were located mainly (69%) in Buenos Aires province. The
      densities of outbreaks (no. of outbreaks per km2) and cattle-demographic
      variables in the province were estimated using a geographical information system
      and kernel function. Before the epidemic officially was recognized, the density
      of outbreaks was correlated (rsp = 0.28-0.47) with the geographic distribution of
      small (< or =100 cattle), dairy and fattening herds. During the mass-vaccination
      campaign to control the epidemic (April-July), the density of outbreaks was most
      strongly correlated (rsp = 0.20-0.25) with the distribution of large (>500
      cattle) and breeding herds. After the end of the mass-vaccination campaign, large
      herds and number of cows were most strongly correlated (rsp = 0.16-0.26) with
      outbreak density. These relationships might indicate that: (1) the disease spread
      more rapidly or was more easily detected in intensive production systems at the
      beginning of the epidemic; (2) vaccination and other control methods applied were
      less effective in large, semi-intensive production systems; (3) incomplete
      vaccine protection was responsible for herd outbreaks that occurred after the end
      of the mass-vaccination campaign.

PMID- 15488274
TI  - Methods for isolation and confirmation of Vibrio vulnificus from oysters and
      environmental sources: a review.
AB  - The gram-negative bacterium Vibrio vulnificus is a natural inhabitant of
      estuarine waters and poses a significant health threat to humans who suffer from
      immune disorders, liver disease, or hemochromatosis (iron overload). V.
      vulnificus enters human hosts via wound infections or consumption of raw
      shellfish (primarily oysters), and infections frequently progress to septicemia
      and death in susceptible individuals. Prevalence in waters and shellfish is not
      correlated with fecal indicator organisms; therefore, species-specific detection
      and enumeration of V. vulnificus in the environment has become a priority for
      agencies that are responsible for shellfish safety. The many selective
      differential media developed for isolation of Vibrio spp., and specifically for
      V. vulnificus detection, are reviewed here; however, none of the media developed
      to date combines the sensitivity to low numbers with the specificity necessary to
      inhibit growth of other organisms. Therefore, immunological and molecular
      protocols are needed for confirmation of the identity of the organism and are
      discussed in detail. Methods under development that hold promise for rapid,
      accurate, and sensitive detection and enumeration of the organism include
      multiplex and real-time PCR. Developing technologies that have proven useful for
      detection and investigation of other pathogens such as biosensors, spectroscopy
      and microarrays may provide the next generation of tools for investigation of the
      prevalence and ecology of V. vulnificus.

PMID- 15488275
TI  - Progress curve analysis for enzyme and microbial kinetic reactions using explicit
      solutions based on the Lambert W function.
AB  - We present a simple method for estimating kinetic parameters from progress curve
      analysis of biologically catalyzed reactions that reduce to forms analogous to
      the Michaelis-Menten equation. Specifically, the Lambert W function is used to
      obtain explicit, closed-form solutions to differential rate expressions that
      describe the dynamics of substrate depletion. The explicit nature of the new
      solutions greatly simplifies nonlinear estimation of the kinetic parameters since
      numerical techniques such as the Runge-Kutta and Newton-Raphson methods used to
      solve the differential and integral forms of the kinetic equations, respectively,
      are replaced with a simple algebraic expression. The applicability of this
      approach for estimating Vmax and Km in the Michaelis-Menten equation was verified
      using a combination of simulated and experimental progress curve data. For
      simulated data, final estimates of Vmax and Km were close to the actual values of
      1 microM/h and 1 microM, respectively, while the standard errors for these
      parameter estimates were proportional to the error level in the simulated data
      sets. The method was also applied to hydrogen depletion experiments by mixed
      cultures of bacteria in activated sludge resulting in Vmax and Km estimates of
      6.531 microM/h and 2.136 microM, respectively. The algebraic nature of this
      solution, coupled with its relatively high accuracy, makes it an attractive
      candidate for kinetic parameter estimation from progress curve data.

PMID- 15488276
TI  - Quantification of denitrifying bacteria in soils by nirK gene targeted real-time
      PCR.
AB  - Denitrification, the reduction of nitrate to nitrous oxide or dinitrogen, is the
      major biological mechanism by which fixed nitrogen returns to the atmosphere from
      soil and water. Microorganisms capable of denitrification are widely distributed
      in the environment but little is known about their abundance since quantification
      is performed using fastidious and time-consuming MPN-based approaches. We used
      real-time PCR to quantify the denitrifying nitrite reductase gene (nirK), a key
      enzyme of the denitrifying pathway catalyzing the reduction of soluble nitrogen
      oxide to gaseous form. The real-time PCR assay was linear over 7 orders of
      magnitude and sensitive down to 10(2) copies by assay. Real-time PCR analysis of
      different soil samples showed nirK densities of 9.7x10(4) to 3.9x10(6) copies per
      gram of soil. Soil real-time PCR products were cloned and sequenced. Analysis of
      56 clone sequences revealed that all cloned real-time PCR products exhibited high
      similarities to previously described nirK. However, phylogenetic analysis showed
      that most of environmental sequences are not related to nirK from cultivated
      denitrifiers.

PMID- 15488277
TI  - Comparison of real-time PCR methods for detection of Salmonella enterica and
      Escherichia coli O157:H7, and introduction of a general internal amplification
      control.
AB  - The objectives of this study were to compare different real-time PCR-based
      methods for detection of either Salmonella spp. or E. coli O157:H7 with respect
      to sensitivity, precision and accuracy. In addition, a general internal
      amplification control (IAC) is presented, allowing prevention of false negative
      results. The IAC allows insight in amplification efficiency and enables a more
      accurate quantification with the evaluated real-time PCR methods. Implementation
      of the IAC with the different PCR methods did not affect the precision of the
      methods, but the sensitivity was reduced 10-fold. Introduction of an IAC with the
      Salmonella enterica specific detection method showed a shift in Ct-value
      (increase of target Ct-value with 0.45+/-0.17 cycles), while with the method to
      detect E. coli O157:H7 no influence of IAC co-amplification was observed. The
      quantification threshold of the methods in which the IAC was included was
      determined at 1 pg of target DNA (equal to 200 CFU) per reaction. Qualitative
      detection was feasible down to 10 fg of target DNA per reaction using both
      methods in which the IAC was incorporated. The adjusted methods have the
      potential to provide fast and sensitive detection of Salmonella spp. or E. coli
      O157:H7, enabling accurate quantification and preventing false negative results
      by using the general IAC.

PMID- 15488278
TI  - Improved methods for mutacin detection and production.
AB  - Studies of mutacins have always been hampered by the difficulties in obtaining
      active liquid preparations of these substances. In order to be commercially
      produced, good mutacin yields have to be obtained, preferably in inexpensive
      media. The results presented here indicate that mutacins can be produced in
      supplemented cheese whey permeate. The influence of carbon and nitrogen
      supplements on mutacin production varied according to the producer strain. The
      use of CaCO3 as a buffer in batch cultures resulted in improved yields of mutacin
      in the supernatants. Antimicrobial activity assays were improve by acidification
      of the diluent (pH 2) and were less variable in peptone water (0.5%). The culture
      medium consisting of cheese whey permeate (6% w/v), yeast extract (2% w/v) and
      CaCO3 (1% w/v) was found to be an inexpensive medium for the efficient production
      of mutacins.

PMID- 15488279
TI  - Comparison of two standardisation methods in real-time quantitative RT-PCR to
      follow Staphylococcus aureus genes expression during in vitro growth.
AB  - By real-time quantitative PCR (RTQ-PCR), two different standardisation methods
      were used to quantify expression of three target genes (RNAII and RNAIII
      transcripts of agr locus and ica transcript of icaADBC locus): (i) a relative
      quantification, using a transcript of three housekeeping genes (gyrase A, gyrA;
      guanylate kinase, gmk and 16S rRNA, 16S) as internal standard, and (ii) an
      absolute quantification, using cloned sequences of the target genes in known
      concentrations as external standards. To determine the efficiency and reliability
      of these two methods, the gene expressions were studied during the growth of a
      clinical isolate of Staphylococcus aureus. Between 3 and 20 h after inoculation,
      target gene transcription was analysed using LightCycler Apparatus, LC Data
      Analysis software and RelQuant software for relative quantification (Roche). For
      all target genes, the expression profiles obtained with gyrA or gmk as internal
      standards remained almost identical. However, these profiles varied between each
      other depending on the standard gene. Due to their important expression
      variations during growth phases, these two housekeeping genes seem inappropriate
      to be used as internal standards. The absolute quantification of the three
      transcripts of interest gave results similar to their relative quantification
      expressed versus 16S rRNA. Therefore, our study suggests the suitable use of 16S
      rRNA as internal standard in RTQ-PCR quantification of staphylococcal gene
      expression during the stationary phase of growth.

PMID- 15488280
TI  - Methods to maximise the staining of fungal propagules with fluorescent dyes.
AB  - The spores and conidia of most fungi have very thick and resistant cell walls
      that severely impede the staining with fluorescent dyes to allow epifluorescence
      microscopy to be employed for their direct detection and quantification in
      natural habitats. In this study, oxidation by sodium hypochlorite and microwave
      irradiation (MWI) were used to enhance the staining of Aspergillus fumigatus and
      Penicillium brevicompactum conidia with six fluorescent dyes. Sodium hypochlorite
      resulted in high percentages of stained conidia (up to 98.8% with 4',6-diamidino
      2-phenylindole [DAPI]), but had to be removed prior to staining with consequent
      heavy conidia losses. By contrast, MWI gave very high percentages, while its
      enhancement of fluorescence intensity facilitated observation by epifluorescence
      microscopy.

PMID- 15488281
TI  - Use of heterotrophic CO2 assimilation as a measure of metabolic activity in
      planktonic and sessile bacteria.
AB  - We have examined whether assimilation of CO2 can be used as a measure of
      metabolic activity in planktonic and sessile heterotrophic bacteria. CO2
      assimilation by environmental samples and pure cultures of heterotrophic bacteria
      was studied using 14CO2 and 13CO2 as tracers. Heterotrophic growth on complex
      organic substrates resulted in assimilation of CO2 into cell biomass by activated
      sludge, drinking water biofilm, and pure cultures of Escherichia coli ATCC 25922,
      Es. coli ATCC 13706, Rhodococcus ruber, Burkholderia sp., Bacillus circulans,
      Pseudomonas putida, Pseudomonas stutzeri, and Pseudomonas aeruginosa. Analysis of
      13C-labelled phospholipid fatty acids (PLFAs) confirmed that heterotrophic
      bacteria may assimilate 13CO2 into cell macromolecules such as membrane lipids.
      All major PLFAs extracted from activated sludge and drinking water biofilm
      samples were enriched in 13C after incubation with CO2. Between 1.4% and 6.5% of
      the biomass produced by cultures of P. putida and a drinking water biofilm during
      growth in complex media was apparently derived from assimilation of CO2. Resting
      cells assimilated less CO2 compared to actively growing cells, and CO2
      assimilation activity correlated with the amount of biomass produced during
      heterotrophic growth. The 14CO2 assimilation assay was evaluated as a tool to
      examine inhibitory effects of biocides on planktonic and sessile heterotrophs
      (biofilms). On the basis of 14CO2 assimilation activity, the minimum inhibitory
      concentration (MIC) of benzalkonium chloride was estimated to 21.1 and 127.2 mg
      l(-1) for planktonic and biofilm samples, respectively. The results indicate that
      assimilation of isotopically labelled CO2 can be used as a relatively simple
      measure of metabolic activity in heterotrophic bacteria. CO2 assimilation assays
      may be used to study the effects of antimicrobial agents on growth and survival
      of planktonic and sessile heterotrophic organisms.

PMID- 15488282
TI  - Three-dimensional biofilm structure quantification.
AB  - Quantitative parameters describing biofilm physical structure have been extracted
      from three-dimensional confocal laser scanning microscopy images and used to
      compare biofilm structures, monitor biofilm development, and quantify
      environmental factors affecting biofilm structure. Researchers have previously
      used biovolume, volume to surface ratio, roughness coefficient, and mean and
      maximum thicknesses to compare biofilm structures. The selection of these
      parameters is dependent on the availability of software to perform calculations.
      We believe it is necessary to develop more comprehensive parameters to describe
      heterogeneous biofilm morphology in three dimensions. This research presents
      parameters describing three-dimensional biofilm heterogeneity, size, and
      morphology of biomass calculated from confocal laser scanning microscopy images.
      This study extends previous work which extracted quantitative parameters
      regarding morphological features from two-dimensional biofilm images to three
      dimensional biofilm images. We describe two types of parameters: (1) textural
      parameters showing microscale heterogeneity of biofilms and (2) volumetric
      parameters describing size and morphology of biomass. The three-dimensional
      features presented are average (ADD) and maximum diffusion distances (MDD),
      fractal dimension, average run lengths (in X, Y and Z directions), aspect ratio,
      textural entropy, energy and homogeneity. We discuss the meaning of each
      parameter and present the calculations in detail. The developed algorithms,
      including automatic thresholding, are implemented in software as MATLAB programs
      which will be available at site prior to publication of the paper.

PMID- 15488283
TI  - Rapid detection of gyrA and parC mutations in fluoroquinolone-resistant Neisseria
      gonorrhoeae by denaturing high-performance liquid chromatography.
AB  - The detection of DNA sequence variation is fundamental to the identification of
      the genomic basis of phenotypic variability. Denaturing high-performance liquid
      chromatography (DHPLC) is a novel technique that is used to detect mutations in
      human DNA. This is the first report that this technique is used as a tool to
      detect mutations in genes encoding fluoroquinolone resistance in Neisseria
      gonorrhoeae. Eighty-one strains of N. gonorrhoeae were used in this study.
      Genomic DNA from each strain was subjected to PCR amplification of 225 bp in gyrA
      and 166 bp in parC spanning the fluoroquinolone-resistance determining regions
      (QRDRs). After we performed DNA sequencing of these amplicons and identification
      of mutations in the QRDRs, DHPLC was undertaken to investigate whether its
      results correlate the distinctive chromatogram with their DNA mutations pattern.
      The profilings detected by DHPLC completely corresponded to the results of the
      DNA sequencing in mutation patters in gyrA and parC genes. They resulted in the
      following amino acid substitutions: Ser-91Phe, Asp-95Gly, and Asp-95Asn in gyrA;
      and Gly-85Asp, Asp-86Asn, Ser-87Arg, and Ser-88Pro in parC, respectively. These
      mutations existed alone or as combinations, and we identified five mutations
      patterns in gyrA and six in parC including wild-type. These mutations and their
      patterns could be rapidly and reproducibly identified from the PCR products using
      DHPLC, producing specific peak patterns that correlate with genotypes. This novel
      detection system facilitates the detection of resistance alleles, providing a
      rapid (5 min per sample), economic (96 sample per run), and reliable technique
      for characterizing fluoroquinolone resistance in N. gonorrhoeae.

PMID- 15488284
TI  - "Paraffin wax-overlay of pour plate", a method for the isolation and enumeration
      of purple non-sulfur bacteria.
AB  - A modification of pour plate technique with an overlay of wax was used for
      isolation and enumeration of purple non-sulfur bacteria (PNSB) with equal
      efficiency as that of agar shake culture. The total count of PNSB ranged from
      10(5)-10(8) CFU g dry soil(-1) and belonged to the genera of Rhodobacter,
      Rhodopseudomonas, Rhodocista and Rubrivivax.

PMID- 15488285
TI  - Simplified sample preparation using frame spotting method for direct counting of
      total bacteria by fluorescence microscopy.
AB  - A new preparation method for direct counting of bacteria in liquid samples with
      fluorescence microscope was developed using a glass slide coated with 3
      aminopropyltriethoxy silane and ring-shaped polyester seal as a retainer. The
      experimental steps of this method were spotting samples onto the coated slides
      with the seal, drying under vacuum, staining with SYBR Green II, drying and
      covering with immersion oil and coverslip to allow counting. This simplified
      method provided consistent results when compared with the conventional filtration
      method for fluorescence microscopy, and is rapid, inexpensive and reproducible.

PMID- 15488286
TI  - A new method of DNA preparation for pulsed-field gel electrophoresis analysis.
AB  - We have developed a new, labour-saving method of preparation, handling and
      treatment of DNA-containing agarose plugs for pulsed-field gel electrophoresis
      (PFGE). A plastic mould in which plugs are formed and supported during DNA
      purification and digestion was designed and successfully tested in a prototype
      device.

PMID- 15488287
TI  - Multiple actions of extracellular ATP and adenosine on calcium currents mediated
      by various purinoceptors in neurons of nucleus tractus solitarius.
AB  - Whole-cell patch-clamp recordings were performed on freshly dissociated nucleus
      tractus solitarius (NTS) of rat to determine the action of extracellular
      adenosine 5'-triphosphate (ATP) and adenosine (ADO) on voltage-dependent calcium
      channel (VDCC) currents (I(Ca)). Application of ATP and ATP-analog inhibited
      I(Ca). The rank order of potency of inhibition of I(Ca) was 2-methylthioATP (2
      MeSATP) > ATP > adenosine 5'-diphosphate (ADP) >> alpha,beta-methylene ATP
      (alpha,beta-MeATP) = uridine 5'-triphosphate (UTP). Application of ADO receptor
      agonists also inhibited I(Ca). The rank order of potency of inhibition of I(Ca)
      was N(6)-cyclohexyladenosine (CHA) > ADO > 2-(4-(2
      carboxyethyl)phenylethylamino)adenosine-5'-N-ethylcarboxamideadenosine (CGS
      21680) > N(6)-2-(4-aminophenyl)ethyladenosine (APNEA). Application of prepulse
      attenuated these inhibition. Both intracellular dialysis of guanosin 5'-O-(2
      thiodiphosphate) (GDP-beta-S) and anti-G(i) antibody also attenuated these
      inhibition. L-, N- and P/Q-type VDCCs were inhibited by ATP. In contrast, N- and
      P/Q-type VDCCs were inhibited by ADO. In addition to inhibition, application of
      100 microM ATP facilitated I(Ca). Intracellular dialysis of GDP-beta-S did not
      attenuate these facilitations. In conclusion, activation of P2Y purinoceptors
      inhibits L-, N- and P/Q-types VDCCs via G(i)-protein betagamma subunits.
      Activation of A(1) and/or A(2) receptors inhibit N- and P/Q-types VDCCs via G(i)
      protein betagamma subunits. Activation of P2X purinoceptors facilitates Ca(2+)
      entry in NTS.

PMID- 15488288
TI  - The immunosuppressant FK506 activates capsaicin- and bradykinin-sensitive DRG
      neurons and cutaneous C-fibers.
AB  - Immunosuppressant drug FK506, which is widely used for the treatment of atopic
      dermatitis, has multiple actions on the nervous system. In order to elucidate the
      mechanisms underlying transient burning sensation elicited by topical application
      of FK506 to the skin of atopic patients, we investigated if FK506 directly
      activates sensory neurons and fibers, or not. Ca(2+) imaging study on cultured
      DRG neurons of rats revealed that application of FK506 raised intracellular
      Ca(2+) levels in a subpopulation of small DRG neurons (3.1% of DRG neurons
      responsive to high K(+) solution). When DRGs from inflamed rats were used, the
      incidence increased to 7.4%. FK506 sensitive neurons also responded to a
      subsequent application of capsaicin (89.5% in normal, and 100% in inflamed rats)
      and bradykinin (31.6% in normal, and 80.9% in inflamed rats). Single fiber
      recordings in the skin-nerve preparation confirmed the results of cell culture
      study, showing that application of FK506 enhanced neuronal discharges of single C
      fibers that are responsive to heat and bradykinin. These findings, taken
      together, indicate that FK506 application on inflamed skin may activate
      nociceptive C-fibers, which bear bradykinin receptors and capsaicin-sensitive
      heat transducer of TRP family, TRPV1.

PMID- 15488289
TI  - Rostrocaudal distribution of spinal respiratory motor activity in an in vitro
      neonatal rat preparation.
AB  - The distribution of inspiratory and expiratory activities among rib-cage muscles
      was examined using isolated brainstem-spinal cord-rib preparations from neonatal
      rats. Expiratory activity was evoked by decreasing perfusate pH from 7.4 to 7.1.
      All internal intercostal muscles (IIMs) in the first to eleventh intercostal
      spaces showed expiratory bursts. Although the IIMs in the more caudal interspaces
      exhibited expiratory bursts for as long as the low pH solution was present in all
      preparations, the expiratory bursts obtained from the IIMs in the rostral
      interspaces gradually disappeared even under low pH conditions in about half the
      preparations, suggesting that the more caudal IIMs play the greater role in
      expiration. All thoracic ventral roots examined from T1VR-T11VR, but not T13VR,
      exhibited overt inspiratory bursts under normal pH conditions. Low pH solution
      induced additional expiratory bursts in all thoracic VRs. The ratio of the
      integral of the absolute electrical voltage during the expiratory phase to that
      during the inspiratory phase increased progressively and significantly from the
      rostral to the caudal interspaces. These results accord well with previous ones
      in mammals in vivo. Hence, the neuronal mechanisms necessary for a rostrocaudal
      gradient in spinal respiratory motor outputs seem to be preserved in this in
      vitro preparation.

PMID- 15488290
TI  - Perivascular nerves induce cardiorespiratory reflexes in response to algogens in
      anaesthetised rats.
AB  - In the present study we measured cardiovascular and respiratory reflexes evoked
      by administration of bradykinin and capsaicin into the hindlimb vasculature of
      anaesthetised rats, whilst simultaneously recording activity of sensory afferents
      on the adventitial surface of femoral arteries and veins. Bradykinin (0.9 nmol)
      and capsaicin (0.3 nmol) caused a rapid reflex fall in mean arterial pressure
      (delta mmHg: -37 +/- 8 and -28 +/- 3, respectively; P < 0.01) and an increase in
      respiratory minute volume (delta ml min(-1): 180.0 +/- 39.2 and 156.1 +/- 24.5,
      respectively; P < 0.01), associated with an increase in neural discharge in
      arterial afferents (from basal 0.4 +/- 0.3 to 8.5 +/- 2.9 impulses s(-1)
      following intra-arterial administration of bradykinin, P < 0.05, n = 7; from
      basal 0.2 +/- 0.1 to 7.5 +/- 3.7 impulses s(-1) with capsaicin, P < 0.01, n =
      18). The antagonists FR173657 and capsazepine confirmed bradykinin B2 and
      vanilloid VR1 receptors mediated the responses to bradykinin and capsaicin,
      respectively. Topical administration of algogen to the vessel surface, and
      electrical stimulation of the adventitia also evoked cardiovascular and
      respiratory responses. These data support the hypothesis that stimulation of
      sensory nerve endings within the hindlimb vasculature contributes to systemic
      cardiorespiratory reflexes in the rat.

PMID- 15488291
TI  - Theta wave amplitude and frequency are differentially correlated with pontine
      waves and rapid eye movements during REM sleep in rats.
AB  - The present study examined the correlations between the dynamics of hippocampal
      theta waves and pontine waves (P waves) and rapid eye movements (REMs) densities
      during REM sleep. Theta wave peak frequency and theta amplitude were estimated as
      the parameters of theta wave dynamics in each 3s segment. The peak frequency and
      theta amplitude were positively correlated with P wave and REMs densities,
      however their detailed correlation properties were distinct from each other.
      Dependency of peak frequency on P wave/REMs density did not change significantly
      from that on REMs/P wave density. On the other hand, dependency of the theta
      amplitude on P wave/REMs density significantly increased with an increased REMs/P
      wave density. Because hippocampal theta waves and P waves are involved in
      learning and memory functions during REM sleep, the correlation between theta
      parameters and P wave density might help to clarify these functions.

PMID- 15488292
TI  - Protective actions of various local anesthetics against the membrane dysfunction
      produced by in vitro ischemia in rat hippocampal CA1 neurons.
AB  - Local anesthetics block not only the Na(+) but also the K(+) and Ca(2+) channels
      in the mammalian neurons. It is well known that lidocaine has neuroprotective
      actions against the ischemic insult of neurons in the central nervous system. In
      order to elucidate how other local anesthetics as well as lidocaine show the
      neuroprotective effects against in vitro ischemic insult, intracellular
      recordings were made from CA1 pyramidal neurons in rat hippocampal slices.
      Superfusion with the medium deprived of oxygen and glucose (in vitro ischemia)
      produced a rapid depolarization after 5 min of exposure. When the normal medium
      was immediately reintroduced after the rapid depolarization, the membrane
      depolarized further (persistent depolarization), the neurons showed no functional
      recovery. Pretreatment with tetracaine, bupivacaine, procaine, lidocaine,
      mepivacaine, or dibucaine (10 or 300 microM) prolonged the latency of the rapid
      depolarization, and most of the drugs partially restored the membrane potential
      toward the pre-exposure level after the reintroduction. Judging from the
      neuroprotective actions such as the prolongation and the potential recovery by
      these drugs, lidocaine, bupivacaine, and dibucaine are candidates for the
      therapeutic use against the ischemic insult. Suppression of the regenerative
      Na(+) conductance is somehow involved in the neuroprotective actions of local
      anesthetics.

PMID- 15488293
TI  - Angiotensin type 2 receptor neuroprotection against chemical hypoxia is dependent
      on the delayed rectifier K+ channel, Na+/Ca2+ exchanger and Na+/K+ ATPase in
      primary cortical cultures.
AB  - We have previously reported that angiotensin II (Ang II) protects cortical
      neurons from chemical-induced hypoxia through activation of the angiotensin type
      2 (AT(2)) receptor. Here, we show in mouse primary neuronal cultures that the
      AT(2) receptor neuroprotection results from the activation of the delayed
      rectifier K(+) channel as well as the involvement of the Na(+)/Ca(2+) exchanger
      (NCX) and Na(+)/K(+) ATPase (ATPase). Roles of the K(+) channel, NCX and ATPase
      were determined using the specific blockers alpha-dendrotoxin, KB-R7943 and
      ouabain, respectively. Sodium azide (10mM) induced apoptosis in 40% of neurons.
      Inhibition of the AT(1) receptor with losartan (1 microM) facilitated angiotensin
      II mediated neuroprotection by reducing sodium azide-induced apoptosis 61.8 +/-
      5.6%, while inhibition of the AT(2) receptor with PD123319 (1 microM) showed no
      neuroprotection. These results suggest that angiotensin II neuroprotection is
      mediated through the AT(2) receptor and requires inhibition of the AT(1) receptor
      in order to facilitate its effect. To determine the roles of delayed rectifier
      K(+) channel, NCX and ATPase cultures were pretreated with alpha-dendrotoxin
      (10nM), KB-R7943 (100 nM) and ouabain (100 nM), which significantly attenuated
      AT(2) receptor mediated neuroprotection. These findings further suggest that the
      mechanism of AT(2) receptor mediated neuroprotection is coupled to activation of
      the delayed rectifier K(+) channel, NCX and ATPase.

PMID- 15488294
TI  - Appearance of high-frequency alpha band with disappearance of low-frequency alpha
      band in EEG is produced during voluntary abdominal breathing in an eyes-closed
      condition.
AB  - This study examined the effects of voluntary abdominal breathing (VAB) on the
      electroencephalogram (EEG) in 22 healthy subjects. VAB was characterized by
      prolonged rhythmic contraction of abdominal muscles for 20 min in an eyes-closed
      condition. The breathing rate was instructed to be very slow, i.e., 3-4
      breaths/min (inspiratory time for 6-8s and expiratory time for 9-12s). A low
      frequency alpha band appeared immediately after eye closing, but it later
      disappeared and was replaced by a new development of a high-frequency alpha band
      4-5 min after the onset of VAB. The subjects had a feeling of vigor-activity with
      a tendency of reduced anxiety during and/or after VAB, as assessed by POMS and
      STAI questionnaire scores. On the other hand, during resting in the eye-closed
      condition, the disappearance of the low-frequency alpha band was replaced by the
      occurrence of a theta/delta band. The subjects became drowsy in this condition.
      We therefore conclude that the increase in high-frequency alpha activity is
      linked to the state of vigor-activity with a tendency of reduced anxiety. Since
      the urinary serotonergic level significantly increased after the VAB, we suggest
      that the serotonergic neurons within the brain may produce the changes in the EEG
      patterns.

PMID- 15488295
TI  - Effect of diazoxide on regulation of vesicular and plasma membrane GABA
      transporter genes and proteins in hippocampus of rats subjected to picrotoxin
      induced kindling.
AB  - Epileptiform discharges and behavioral seizures may be the consequences of excess
      excitation from inadequate inhibitory effects associated with gamma-aminobutyric
      acid (GABA). GABA is taken up and accumulated in synaptic vesicles by the action
      of vesicular GABA transporter (VGAT) before its release into the synaptic cleft,
      and removed from synaptic regions by the action of transporter proteins GABA
      transporter-1 (GAT-1) and GABA transporter-3 (GAT-3). In this experiment, the
      effects of diazoxide (DIZ) on the VGAT, GAT-1 and GAT-3 mRNA and protein levels
      in hippocampus, and on the seizure activities of picrotoxin (PTX)-induced
      kindling rats were observed. DIZ caused increase in the quantity of VGAT mRNAs
      and proteins, and down regulation of GABA transporters GAT-1 and GAT-3 mRNAs and
      proteins after the PTX re-kindling. Furthermore, DIZ produced not only a prompt
      but also a later suppression of PTX-induced seizures. Although DIZ has effects on
      ATP-sensitive potassium (K(ATP)) channels when measured in vitro, our study
      suggests that additional mechanisms of action may involve the regulation of GABA
      transporters, which may aid in understanding epileptogenesis and inform
      investigators about future design and development of K(ATP) channel openers to
      treat epilepsy.

PMID- 15488296
TI  - Theta oscillation in the human anterior cingulate cortex during all-night sleep:
      an electrocorticographic study.
AB  - Ten epileptic patients each with subdural electrodes surgically attached to the
      anterior cingulate cortex (ACC; two cases), the orbitofrontal cortex (OFC; seven
      cases), or both (one case) were included in this study. We recorded each
      patient's ACC or OFC electrocorticogram (ECoG) during the time period that the
      patient was awake and naturally asleep. We performed a Fast Fourier
      Transformation (FFT) power spectral analysis on each ECoG to examine its
      frequency component. We found that the ACC showed regular and continuous theta
      oscillation (5-7Hz) during wakefulness and rapid eye movement (REM) sleep, but
      not during slow wave sleep. Theta waves observed in REM sleep were not as
      distinct as those found in wakefulness. We also discovered that the orbitofrontal
      signals represented spectral peaks in the theta band only during wakefulness.
      This suggests the coexistence of theta oscillation in the ACC. Considering our
      previous observations of gamma and beta oscillations in the human hippocampus, we
      hypothesize that the human limbic system manifests two oscillatory activities.
      The results obtained in this study suggest that electrophysiological activity in
      the ACC could be related to particular psychological functions in wakefulness and
      in REM sleep. These results are useful in elucidating the human brain mechanism.

PMID- 15488297
TI  - Opioid inhibition of GABAergic neurotransmission in mechanically isolated rat
      periaqueductal gray neurons.
AB  - The descending pain control system is activated by opioid peptides mainly at the
      midbrain periaqueductal gray (PAG). Although activation of presynaptic opioid
      receptors has been reported to inhibit gamma-aminobutyric acid (GABA) release,
      the exact electrophysiological mechanisms are controversial. To elucidate the
      mechanisms involved in the opioid modulation of presynaptic GABA release, we
      isolated single PAG neurons with functionally intact synaptic terminals by a
      mechanical dissociation in the absence of enzyme. With the conventional whole
      cell recording mode under the voltage-clamp conditions, the spontaneous miniature
      inhibitory postsynaptic currents (mIPSCs) were recorded. Bicuculline completely
      and reversibly blocked mIPSCs. A specific mu-opioid agonist, [d-Ala(2),N-Me
      Phe(4),Gly(5)-ol]-enkephalin (DAMGO), reversibly reduced the frequency of mIPSCs
      without any alteration of amplitude. The inhibitory effect of DAMGO was blocked
      by N-ethylmaleimide. Blockade of presynaptic Ca(2+) influx by cadmium or
      depletion of extracellular Ca(2+) did not alter the DAMGO inhibition. In
      addition, K(+) channels blockers, Ba(2+) or 4-aminopyridine, did not affect the
      DAMGO effect. The present study indicates that activation of presynaptic mu
      opioid receptors coupled to G-proteins inhibits GABA release through unknown
      intracellular mechanisms downstream of Ca(2+) influx.

PMID- 15488298
TI  - Dopaminergic modulation on respiratory rhythm in rat brainstem-spinal cord
      preparation.
AB  - Dopamine (DA) is known to regulate both higher order and autonomic brain
      functions. To elucidate the effects of DA on respiratory rhythm generation,
      isolated brainstem-spinal cord was treated with DA and each DA receptor agonist
      individually. DA application facilitated respiratory rhythm in pons-medulla
      spinal cord preparations, but depressed it in medulla-spinal cord preparations.
      Furthermore, we found that DA application depressed Pre-Inspiratory (Pre-I)
      neurons but not Inspiratory or Expiratory neurons and that among the various DA
      receptor agonists, only a D4 agonist, PD168077, depressed respiratory rhythm.
      Therefore, the primary target of DA action in modulating respiratory rhythm
      generation is the Pre-I neurons in the medulla.

PMID- 15488299
TI  - Purkinje cell functions in the in vitro cerebellum isolated from neonatal rats in
      a block with the pons and medulla.
AB  - The cerebellum dissected from neonatal rats in a block including the pons and
      medulla and maintained in a modified Krebs solution provides a unique preparation
      of brain tissue with preserved major fiber connections. Electrophysiological and
      optical recordings revealed that, at postnatal days 4-8 (P4-P8), Purkinje cells
      in the lateral portion of the cerebellum responded to the stimulation of climbing
      fiber afferents at the inferior olive and of parallel fibers at the posterior
      vermis, and that the combination of these inputs induced long-term depression.
      These observations and pharmacological testings indicate that certain functional
      features of Purkinje cells mature around P5 in the lateral portion of the
      cerebellum.

PMID- 15488300
TI  - Decompressive craniectomy in acute cerebral ischemia in rats. Is there any
      benefit in smaller thromboembolic infarcts?
AB  - Early craniectomy has shown to reduce infarction size in experimental large MCA
      infarction probably due to improved leptomeningeal perfusion. Based on the
      hypothesis that craniectomy may also be beneficial in smaller MCA infarction we
      evaluated the effects of craniectomy on infarction size in small thromboembolic
      cerebral infarction in rats. Therefore, thromboembolic cerebral ischemia was
      induced in 40 rats by endovascular injection of autologous, fibrin-rich emboli.
      Twenty-one animals with a diffusion-weighted MR imaging (DWI)-derived infarction
      size of 50-100 mm3 (involving one- to two-third of the MCA territory) at 1 h
      after injection were randomly assigned to two groups. Eleven animals of group 1
      immediately underwent craniectomy, ten animals of group 2 (controls) were not
      treated. Serial DWI was performed at 4 and 24 h. Infarction size was assessed by
      TTC-staining at 48 h after emboli injection. As result, prior to treatment, at 1
      h after emboli injection, infarction size in groups 1 and 2 was 65.9 +/- 16.0 mm3
      and 67.9 +/- 17.8 mm3, respectively. At 4 and 24 h, infarction size in group 1
      was 73.5 +/- 22.1 mm3 and 85.2 +/- 24.7 mm3, and 76.3 +/- 21.0 mm3 and 83.4 +/-
      22.9 mm3 in group 2, respectively. TTC-derived infarction size was 84.0 +/- 23.3
      mm3 and 82.7 +/- 21.5 mm3, respectively. There was no significant difference
      between the two groups (P > 0.79). In conclusion, our results demonstrate that
      for small thromboembolic MCA infarction early craniectomy is not beneficial.

PMID- 15488301
TI  - Neural correlates of internally-generated disgust via autobiographical recall: a
      functional magnetic resonance imaging investigation.
AB  - Converging lines of evidence suggest the involvement of the insula and basal
      ganglia in the processing of disgust, an important primary emotion that guides
      the avoidance of potential physical contamination and disease. Prior human lesion
      and functional brain imaging studies have employed exteroceptive sensory stimuli
      such as facial expressions of disgust, and disgust-eliciting pictures. Thus, the
      neural substrates underlying the internal experience of disgust remain unknown.
      The present fMRI study examined the neural correlates of self-induced disgust
      aided by the recall and re-experience of personally salient life events. Subjects
      were scanned while they recalled and re-experienced either a recent situation
      that evoked intense disgust or a time-matched, equally vivid neutral/non
      emotional event. Relative to the emotionally neutral condition, self-induced
      disgust was associated with activation of the insula, hippocampus, anterior and
      posterior cingulate cortex, basal ganglia, thalamus, and primary visual cortex.
      These findings suggest that areas previously associated with the perception of
      disgust (e.g., insula, basal ganglia) are also involved interoceptive experience
      of disgust.

PMID- 15488302
TI  - Time-series pattern changes related to movement rate in synchronized human
      tapping.
AB  - We investigated the effect of movement rate on the time-series properties of
      human synchronization errors by applying power spectrum analysis and detrended
      fluctuation analysis (DFA). Participants were required to execute a finger
      tapping task with their right index finger in synchrony with periodic sounds
      under seven conditions of movement rates ranging from 1 to 4 Hz and separated by
      0.5 Hz. At slow movement rates (1 and 1.5 Hz), the power spectrum of the
      synchronization errors flattened in the low-frequency portion, resulting in short
      range correlation. At fast movement rates (from 2 to 4 Hz), on the other hand,
      the time series of the timing errors exhibited a 1/fbeta-type long-range
      correlation. These results indicate that the movement rate has an effect on the
      temporal coordination pattern in the human timing control mechanism. We inferred
      that this change in the coordination pattern reflects the transition between
      different states in human synchronization movements with an external signal.

PMID- 15488303
TI  - Scaling down motor memories: de-adaptation after motor learning.
AB  - Although adaptation to novel motor tasks is sometimes a very slow process, de
      adaptation is usually extremely rapid. Such rapid de-adaptation is seen in
      dynamic learning in which subjects can take hundreds of movements to learn a
      novel force environment but only a few movements to de-adapt back to a normal or
      "null" force environment. We investigated whether this effect is unique to the
      null environment or reveals a more general rapid adaptation mechanism by studying
      how subjects behave when their dynamic environment changes. We observed that
      after learning a dynamic force field, subjects took longer to de-adapt when the
      forces were turned off than to adapt to a novel scaled-down version of the
      experienced field. This demonstrates that rapid adaptation is not unique to the
      "null" force environment. Moreover, we examined subjects' ability to adapt from a
      learned field to either a scaled down field or to a field in which the sign of
      the forces changed. Even though in both conditions the required change in force
      output was identical, subjects were significantly faster at adapting to the
      scaled down field. The result suggests that rapid de-adaptation reflects a
      capacity to scale down the relative contribution of existing control modules to
      the motor output.

PMID- 15488304
TI  - The effects of agouti-related protein gene transfer in vivo by electroporation in
      mice.
AB  - In the present study, the cDNA encoding agouti-related protein (AGRP) gene known
      as an orexigenic factor was transferred in vivo to test whether food intake and
      body weight gain is improved in mice. When the expression plasmid of AGRP gene
      driven by mouse beta-actin, pActAGRP, was transferred into leg muscle by
      electroporation, body weight of gene-transferred mice was significantly increased
      at 14 days and afterwards compared with that of control counterparts (p < 0.05).
      Likewise, daily food intake was also significantly higher in the AGRP gene
      transferred mice than in the control mice at 4 days and afterwards (p < 0.05). A
      significant increase in serum AGRP concentration of the AGRP gene-transferred
      group was detected compared with the control group at 1 week (p < 0.01), but the
      difference quickly disappeared at 3 weeks. However, the hypothalamic NPY mRNA
      abundance of AGRP gene-transferred mice was significantly higher than that of the
      control mice at 3 weeks (p < 0.05). These results suggested that instead of
      hormone administration per se, in vivo AGPR gene transfer into skeletal muscle
      was found to mimic hormonal effects. The present methodology of in vivo gene
      transfer by electroporation might be useful to promote growth and food intake in
      farm livestock as well as experimental animals.

PMID- 15488305
TI  - Dopamine in the orbitofrontal cortex regulates operant responding under a
      progressive ratio of reinforcement in rats.
AB  - Prefrontocortical dopamine (DA) plays an essential role in the regulation of
      cognitive functions and behavior. The orbitofrontal cortex (OFC) receives a
      dopaminergic projection from the ventral tegmental area and is particularly
      important for goal-directed appetitive behaviors and for the neural
      representation of reward value. We here examined the effects of DA receptor
      blockers locally infused into the OFC, on instrumental behavior under a
      progressive schedule of reinforcement. After continuous reinforcement training
      (lever pressing for casein pellets) rats received bilateral intra-OFC-infusions
      of the DA D1-receptor antagonist SCH23390 (3 microg/0.5 microl), the DA D2
      receptor antagonist sulpiride (3 microg/0.5 microl), or phosphate buffered saline
      through chronically indwelling cannulae. Immediately after infusion they were
      tested under a time-constrained progressive ratio schedule of reinforcement (3,
      6, 9, 12, ... lever presses for 1 casein pellet within 180 s). Both SCH23390 and
      sulpiride led to a significant reduction of the break point (cessation to respond
      to the increasing criterion of instrumental effort) compared to vehicle
      infusions. A food preference test revealed no drug effects on the amount of
      consumed pellets and on the preference of casein pellets over laboratory chow.
      Leftward shifts of the break point in progressive ratio tasks indicate a
      disturbance of the mechanisms that translate motivation into appetitive behavior
      under conditions of increasing instrumental effort. Therefore, our data indicate
      that orbitofrontal dopamine is necessary for reward-related instrumental
      behavior.

PMID- 15488306
TI  - The mitochondrial toxin, 3-nitropropionic acid, induces extracellular Zn2+
      accumulation in rat hippocampus slices.
AB  - 3-nitropropionic acid (3-NPA), a suicide inhibitor of succinate dehydrogenase
      (SDH; complex II), has been used to provide useful experimental models of
      Huntington's disease (HD) and "chemical hypoxia" in rodents. The trace ion Zn2+
      has been shown to cause neurodegeneration. Employing real-time Newport Green
      fluorescence imaging of extracellular Zn2+, we found that 3-NPA (10-100 microM)
      caused a concentration-dependent increase in the concentration of extracellular
      Zn2+ ([Zn2+]o) in acute rat hippocampus slices. This increase in [Zn2+]o was
      abolished by 10 mM CaEDTA. The increase of [Zn2+]o was also accompanied by a
      rapid increase of cytoplasmic-free Zn2+ concentration ([Zn2+]i). The induction of
      Zn2+ release by 3-MPA in hippocampus slices points to a potential mechanism by
      which 3-NPA might induce neurodegeneration.

PMID- 15488307
TI  - Lateral hypothalamic acetylcholinesterase-immunoreactive neurons co-express
      either orexin or melanin concentrating hormone.
AB  - The lateral hypothalamic area (LHA) contains a large population of neurons that
      express the enzyme acetylcholinesterase (AChE), but are not themselves
      cholinergic. Some of these neurons have been shown to contain melanin
      concentrating hormone (MCH), a neuropeptide implicated in regulating feeding, but
      the identities of the remaining neurons are unknown. We now report that nearly
      all AChE-immunoreactive neurons in the LHA express immunoreactivity for either
      MCH or for orexin, a peptide implicated in regulating wakefulness. Furthermore,
      most orexin neurons and MCH neurons appear to contain AChE. AChE immunoreactivity
      appears to be a key feature of nearly all of the diffusely-projecting cortical
      systems.

PMID- 15488308
TI  - Catechol-O-methyltransferase gene polymorphism is associated with risk of
      psychosis in Alzheimer Disease.
AB  - There is emerging evidence that psychosis in Alzheimer Disease (AD) represents a
      clinically relevant phenotype with a distinct biological process. It has been
      reported that a functional polymorphism of the catechol-O-methyltransferase
      (COMT) gene predisposes to an increased risk for schizophrenia and likely to
      psychosis susceptibility. Aim of this study was to evaluate functional COMT
      genetic variation as a risk factor for psychosis in Alzheimer Disease. One
      hundred eighty-one AD patients and 208 age-matched controls underwent clinical
      and neuropsychological examination, behavioural and psychiatric disturbances
      evaluation, and ApoE and COMT genotyping. The distribution of COMT genotypes did
      not significantly differ in AD compared to controls. Among patients with
      psychosis (32.6%), 88.1% were COMT*H carriers (COMT H/H or COMT H/L, p < .01).
      The Odds Ratio (OR) for risk of psychosis in COMT*H carriers was 2.66 (confidence
      interval, CI 95%: 1.6-6.62), taking into account possible confounding factors. A
      comparable influence of COMT polymorphism on psychosis over the course of the
      disease was reported. These findings suggest that COMT polymorphism influences on
      the risk of psychosis since the early stages, and claims for the possibility to
      identify distinct phenotypes on genetic basis among AD patients.

PMID- 15488309
TI  - Analgesic effect of extracts of Chinese medicinal herbs Moutan cortex and Coicis
      semen on neuropathic pain in mice.
AB  - Neuropathic pain arising from peripheral nerve injury is a clinical disorder
      characterized by a combination of spontaneous pain, hyperalgesia and tactile pain
      (allodynia), and remains a significant clinical problem since it is often poorly
      relieved by conventional analgesics. To seek an analgesic compound(s) in Chinese
      herbs, we examined the effect of seven Chinese herbs that are routinely
      prescribed for pain management in two neuropathic pain models: allodynia induced
      by intrathecal administration of prostaglandin F2alpha (PGF2alpha) and by
      selective L5 spinal nerve transection. The extracts of Moutan cortex and Coicis
      semen dose-dependently alleviated the PGF2alpha-induced allodynia by oral
      administration 1 h before intrathecal injection of PGF2alpha. When orally
      administrated every day for 7 days, these extracts attenuated neuropathic pain in
      the ipsilateral side, but not in the contralateral side, day 7 after L5 spinal
      nerve transection. The increase in NADPH diaphorase activity in the spinal cord
      associated with neuropathic pain was also blocked by these extracts. These
      results suggest that Moutan cortex and Coicis semen contain substances effective
      in neuropathic pain.

PMID- 15488310
TI  - Transient arrest of psychogenic tremor induced by contralateral ballistic
      movements.
AB  - One of the clinical characteristics of psychogenic tremors (PT) is the disruption
      or transient cessation of tremor with distractive manoeuvres, including those
      involving the performance of voluntary movements with the contralateral hand.
      Seven patients with PT, 11 patients with Parkinson's disease (PD), 10 patients
      with essential tremor (ET) and 10 normal volunteers mimicking tremor (NV) were
      requested to perform a fast unilateral wrist movement to close a switch, at the
      perception of a visual cue, either at rest or during maintenance of a posture. We
      measured the time-locked changes in frequency and amplitude occurring in tremor
      oscillations of the contralateral hand. The reaction time task induced a
      significant reduction in amplitude or cessation of contralateral tremor
      oscillations in PT and NV, but not in PD and ET. The effect occurred with a delay
      with respect to the onset of the contralateral movement without significant
      differences in PT versus NV (p > 0.05). The physiological mechanisms accounting
      for the effect seen on tremor of NV and PT may involve the interhemispheric
      inhibition that accompanies the execution of a unilateral motor task. Tremor
      circuits in patients with PD and ET may be impervious to these inhibitory
      commands. The documentation and quantitation of the effects of a ballistic
      movement on contralateral rhythmic activity are of clinical relevance for the
      identification of patients with PT.

PMID- 15488311
TI  - Distribution of heat shock protein 108 mRNA during the development of the chicken
      brain.
AB  - The developmental expression of heat shock protein 108 (HSP108) mRNA was mapped
      in chicken brain using in situ hybridization and reverse transcription-polymerase
      chain reaction (RT-PCR). RT-PCR showed that HSP108 mRNA increased from embryonic
      day 5 (E5) to 13 (E13), significantly decreased from E17 to E21 and then
      increased again at the adult stage. In situ hybridization showed that while
      intense HSP108 positive (HSP108+) signals were localized in the cerebellum from
      E7 to E14, the intensities of these signals were significantly decreased at E17.
      However, at the adult stage, HSP108 expression increased in a cell type dependent
      manner. A decrease in HSP108 mRNA expression during differentiation was also
      observed in an in vitro study of brain cells treated with nerve growth factor
      (NGF).

PMID- 15488312
TI  - Long-term potentiation in the optic tectum of rainbow trout.
AB  - We examined synaptic plasticity in the optic tectum of rainbow trout by
      extracellular recordings. We found that the field-excitatory postsynaptic
      potential in the retinotectal synapses was potentiated by repetitive stimuli of
      1.0 Hz for 20 s to the retinotectal afferents. The long-term potentiation (LTP)
      developed slowly, and was maintained for at least 2 h. Applications of an
      antagonist for N-methyl-D-aspartic acid (NMDA) receptors or Mg2+ -free saline
      showed that activation of NMDA receptors was required to form the LTP beyond the
      induction period. The present findings indicate that presynaptic stimulation in
      the retinotectal synapses causes LTP mediated by NMDA receptors in the optic
      tectum of rainbow trout.

PMID- 15488313
TI  - Chemokines (RANTES and MCP-1) and chemokine-receptors (CCR2 and CCR5) gene
      polymorphisms in Alzheimer's and Parkinson's disease.
AB  - Parkinson's disease (PD) is a complex disorder characterized by the progressive
      degeneration of dopaminergic neurons in the midbrain. Late-onset Alzheimer's
      disease (LOAD) is the most common cause of dementia in the elderly, affecting
      about 5% of the population older than 65 years. Several works have demonstrated
      the involvement of inflammation in the pathogenesis of both, PD and LOAD. Genetic
      susceptibility to develop PD and LOAD has also been widely recognised. Thus,
      functional polymorphisms at the genes encoding inflammatory proteins could
      influence the overall risk of developing these neurodegenerative disorders. We
      examined whether DNA-polymorphisms at the genes encoding chemokines MCP-1 (-2518
      A/G) and RANTES (-403 A/G), and chemokine receptors 5 (CCR5, Delta32) and 2
      (CCR2,V64I), were associated with the risk and/or the clinical outcome of LOAD
      and PD. A total of 200 PD, 326 LOAD, and 370 healthy controls were genotyped for
      the four polymorphisms, and genotype frequencies statistically compared. We did
      not find significant differences in the frequencies of the different genotypes
      between both groups of patients and controls. We conclude that the four DNA
      polymorphisms, which have been associated with several immuno-modulated diseases,
      did not contribute to the risk of PD or LOAD.

PMID- 15488314
TI  - 4-Hydroxynonenal modulates the long-term potentiation induced by L-type Ca2+
      channel activation in the rat dentate gyrus in vitro.
AB  - Increased oxyradical production and membrane lipid peroxidation (MLP) occur under
      physiological and degenerative conditions in neurons. We investigated whether 4
      hydroxynonenal (4HN), one of the membrane lipid peroxidation products, affects
      long-term potentiation (LTP) in the rat dentate gyrus in vitro. Treatment of
      hippocampal slices with 4HN (10 microM) enhanced LTP without affecting basal
      evoked potentials. The enhancement was completely inhibited by 2 microM
      nifedipine, a blocker of L-type Ca2+ channels. In cultured dentate gyrus neurons,
      treatment of the cells with 4HN for 24 h resulted in a significant amount of cell
      death that was detoxified by glutathione, whereas short-term treatment with 4HN
      (< or = 6 h) had no effect. Nifedipine partially but significantly suppressed the
      4HN-induced cell death. These results suggest that 4HN modulates LTP and induces
      delayed cell death through L-type Ca2+ channel activation in the dentate gyrus.
      4HN thereby plays an important role in both physiological and pathophysiological
      events in the hippocampus.

PMID- 15488316
TI  - Suppression of experimental allergic encephalomyelitis in rats by 50-nT, 7-Hz
      amplitude-modulated nocturnal magnetic fields depends on when after inoculation
      the fields are applied.
AB  - Female Lewis rats (n = 88) were inoculated with an emulsion of spinal cord and
      complete Freund's adjuvant. They were then exposed in 11 separate blocks of
      experiments over a year period for approximately 6 min every hour between
      midnight and 08:00 h during post-inoculation nights 1-7, 8-16, 1-16, or 9 and 10
      to 50-nT, 7-Hz, amplitude-modulated magnetic fields or to sham field (control)
      conditions. Compared to the control rats those exposed to the magnetic fields for
      nights 1-7 and nights 9-10 displayed more severe clinical symptoms while those
      exposed for nights 1-16 or 8-16 showed less severe symptoms. There was a strong
      correlation between the severity of the clinical symptoms in the control groups
      and the global geomagnetic activity 9 and 10 days after inoculation. These
      results suggest that the immunosuppressive effects of weak nocturnal magnetic
      fields may depend upon when they are applied during various stages in the
      development of a disease.

PMID- 15488315
TI  - Engineering embryonic stem cell derived glia for adenosine delivery.
AB  - Based on the anticonvulsant and neuroprotective properties of adenosine, and
      based on the long-term survival potential of stem cell derived brain implants,
      adenosine releasing stem cells may constitute a novel tool for the treatment of
      epilepsy. Pluripotency and unlimited self-renewal make embryonic stem (ES) cells
      a particularly versatile donor source for cell transplantation. With the aim to
      test the feasibility of a stem cell-based delivery system for adenosine, both
      alleles of adenosine kinase (ADK), the major adenosine-metabolizing enzyme, were
      disrupted by homologous recombination in ES cells. Adk-/- ES cells were subjected
      to a glial differentiation protocol and, as a result, gave rise to proliferating
      glial precursors, which could be further differentiated into mature astrocytes
      and oligodendrocytes. Thus, a lack of ADK does not compromise the glial
      differentiation potential of ES cells. The Adk-/- ES cells yielded glial
      populations with an adenosine release of up to 40.1 +/- 6.0 ng per 10(5) cells
      per hour, an amount considered to be sufficient for seizure suppression. Our
      findings indicate that Adk-/- ES cells constitute a potential source for
      therapeutic adenosine releasing grafts.

PMID- 15488317
TI  - Mitochondrial polymporphisms in Parkinson's Disease.
AB  - The mtDNA polymorphisms A4336G, A10398G and T4216C have been associated with PD.
      While A4336G is thought to be a genetic risk factor, A10398G appears to be a
      protective factor and T4216C is only weakly associated with the disease. In this
      work we analyzed the association between these three genetic polymorphisms and PD
      in a Spanish-PD population. The samples were classified by ethnic origin in
      Basques or other origin. Our analysis confirm the association between A4336G and
      PD. Our results with A10398G polymorphism highlight the importance of performing
      the association studies in ethnically homogeneous populations.

PMID- 15488318
TI  - Age-related alteration of activity and gene expression of endothelial nitric
      oxide synthase in different parts of the brain in rats.
AB  - Nitric oxide (NO) plays important roles in aging and neurodegeneration. Our
      previous results indicated that aging differently affects NOS isoforms.
      Expression of nNOS mRNA was lower while iNOS was absent at any age. However,
      total NO synthesis increased in aged cerebral cortex and cerebellum as a
      consequence of changes of nNOS phosphorylation state. The question arise how
      aging influences activity and expression of eNOS in different parts of adult and
      aged brain. The levels of eNOS mRNA, protein and activity were measured using RT
      PCR, immuno- and radiochemical methods, respectively. Our studies indicated that
      after inhibition of nNOS with 7-nitroindazole (7-NI) NO synthesis is lower in all
      parts of aged brain comparing to adults. However, eNOS activity significantly
      decreases only in cerebellum. The expression of eNOS determined on mRNA level was
      enhanced in all investigated aged brain parts to 140-190% of adult value and the
      data were statistically significant for cerebral cortex and cerebellum. The
      higher level of mRNA is probably the adaptive response to lower NOS activity.
      However, the Western-blot signal of eNOS protein was unchanged in aged brain
      parts comparing to adults suggesting age-related disturbances of protein
      synthesis and its function. It is also possible that a post-translational
      modification of the enzyme occurs in the aged rat brain. The lower eNOS activity
      in aged brain may significantly affects the signal transduction processes on the
      pathway NO/cGMP/PKG.

PMID- 15488319
TI  - Expression of MATH1, a marker of cerebellar granule cell progenitors, identifies
      different medulloblastoma sub-types.
AB  - In order to look for genetic markers helpful for the biological risk
      stratification of medulloblastomas (MBs) we assayed by real-time PCR expression
      levels of the following genes: MATH1, encoding a critical transcription factor
      for the differentiation of cerebellar granular cells (CGCs); PEDF, that encodes a
      trophic factor for CGCs and is located in a region of frequent allelic imbalance
      in MBs; and BIRC5, encoding the antiapoptotic protein survivin, usually
      overexpressed in malignancies. Expression levels of TRKC, higher in MBs with a
      more favorable prognosis, were also studied. Twenty-three patients were
      considered: MATH1 expression was strong in 14/23 and undetectable in the others.
      PEDF was up-regulated in 8/23, TRKC in 9/23, and BIRC5 in 23/23. MATH1 expression
      was significantly correlated with adult age (p < 0.0001), tumor location in
      hemispheres rather than the vermis (p < 0.0004), and PEDF and TRKC up-regulation
      (p < 0.008 and p < 0.04, respectively). During development MATH1 is selectively
      expressed in the external germinal layer (EGL) of the cerebellum. Thus, MATH1
      expression identifies a subgroup of MBs that derive from the EGL and arise during
      adult age into cerebellar hemispheres. MATH1 mRNA-positive MBs express high
      levels of PEDF and show a trend towards longer survival, in agreement with
      increased expression of TRKC. BIRC5 expression, which is strong in all MBs and
      absent in normal cerebellum, lacks any prognostic value but could be explored for
      selective targeting of therapeutic factors to MBs.

PMID- 15488320
TI  - The potassium channel modulator flupirtine shifts the frequency-response function
      of hippocampal synapses to favour LTD in mice.
AB  - Flupirtine is a centrally acting nonopioid analgesic with muscle-relaxant
      properties. Flupirtine has been found to activate inwardly rectifying potassium
      conductances and hence to indirectly inhibit the activation of NMDA receptors.
      NMDA receptor activation is crucial for the induction of long-term potentiation
      (LTP) of synaptic transmission, which is considered as cellular correlate of
      learning and memory and of central sensitization in chronic pain states. Although
      flupirtine has been widely used for the management of pain, its effects on
      synaptic plasticity have not yet been investigated. We, therefore, performed
      extracellular and whole-cell patch-clamp recordings in hippocampal slices of mice
      to examine the effects of flupirtine on synaptic plasticity and neuronal membrane
      properties. Excitatory postsynaptic potentials (EPSPs) in the CA1 region were
      evoked alternately by stimulating two independent Schaffer collateral-commissural
      inputs. LTP and long-term depression (LTD) were induced by different stimulation
      paradigms (100 Hz, 10 Hz, 5 Hz, and 1 Hz). Flupirtine (30 microM) diminished the
      degree of LTP and enhanced LTD. This effect is most likely due to the
      hyperpolarization of CA1 pyramidal neurons and the reduction of their input
      resistance found after application of flupirtine. The observed effects on
      synaptic strength could underly the beneficial effects of flupirtine on different
      types of chronic pain.

PMID- 15488321
TI  - The calcium-responsive transactivator recruits CREB binding protein to nuclear
      bodies.
AB  - The calcium-responsive transactivator (CREST) is required for the normal
      development of neuronal dendritic trees. Here we report that CREST is localized
      to sub-nuclear structures in the rat neuroendocrine pheochromocytoma PC12 cells.
      A yellow fluorescence protein-CREST fusion protein was expressed in HEK 293 and
      PC12 cells and the recombinant protein was exclusively targeted to nuclear
      bodies. A similar result was obtained with a Flag-tagged CREST. Deleting the N
      terminal 148 or the C-terminal 79 amino acid sequences had no effect on
      targeting, whereas removing 164 amino acid residues from the C-terminus abolished
      nuclear body localization. We found that CREST did not co-localize with
      promyelocytic leukaemia oncoprotein (PML) body and was not targeted to PML
      bodies. Overexpression of CREST markedly increased the number of nuclear bodies
      positive for the histone acetyltransferase CREB binding protein (CBP). Double
      immunofluorescence staining of Flag-CREST and CBP suggested that CREST and CBP
      had a high degree of co-localization within the nuclear bodies. Deletion of the
      CBP binding domain of CREST inhibited the recruitment of CBP to CREST nuclear
      bodies. These results suggest that CBP recruitment to nuclear bodies by CREST may
      play an important role in CREST-mediated calcium-responsive transactivation, and
      CREST nuclear body may function as an assembly site for activators/co-activators
      in gene transcription control.

PMID- 15488322
TI  - Monoamine levels after pilocarpine-induced status epilepticus in hippocampus and
      frontal cortex of Wistar rats.
AB  - Pilocarpine-induced status epilepticus (SE) is an useful model to study the
      involvement of neurotransmitter systems as epileptogenesis modulators. Some
      researches have shown that pharmacological manipulations in dopaminergic,
      serotonergic, and noradrenergic systems alter the occurrence of pilocarpine
      induced SE. The control group was treated with 0.9% saline (control group, s.c.).
      Another group of rats received pilocarpine (400mg/kg, s.c.) and both groups were
      sacrificed 24 h after the treatment. This work was performed to determine the
      alterations in monoamine levels (dopamine (DA), serotonin (5-HT) and
      norepinephrine (NE)) and their metabolites (3,4-hydroxyphenylacetic acid (DOPAC),
      homovanilic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA)) after
      pilocarpine-induced SE in hippocampus and frontal cortex of adult rats. The
      monoamines and their metabolites were determined by reverse-phase high
      performance liquid chromatography with electrochemical detection. DA and 5-HIAA
      concentrations were not altered in the hippocampus of the pilocarpine group, but
      in the same group the 5-HT (160%), DOPAC (316%) and HVA (21%) levels increased,
      whereas, the NE (47%) content declined. For the frontal cortex determinations,
      there was an increase of 20 and 72% in DA and DOPAC levels, respectively, and a
      decrease in NE (32%), 5-HT (33%) and 5-HIAA (19%) concentrations, but HVA content
      remained unaltered. These results indicate that pilocarpine-induced SE can alter
      monoamine levels in different ways depending on the brain area studied,
      suggesting that different mechanisms are involved.

PMID- 15488323
TI  - Functional effects of cocaine self-administration in primate brain regions
      regulating cardiovascular function.
AB  - Cocaine abuse is associated with autonomic dysregulation, such as altered blood
      pressure and heart rate. Both central and peripheral mechanisms have been
      implicated in mediating these changes, however, to date, no study has examined
      functional changes in activity within central autonomic-associated brain regions
      in response to cocaine in non-human primates. The aim of the present study was to
      measure local cerebral glucose utilization, in selected autonomic brain regions,
      in rhesus monkeys that had self-administered cocaine (0.3 mg/kg/infusion) for 5
      days (initial) or 100 days (chronic). Measurements were compared with control
      monkeys, in which responding was maintained by food reinforcement. In general,
      decreased rates of glucose utilization were observed in targeted areas following
      both 5 and 100 days of cocaine self-administration compared to control values.
      However, after initial stages of cocaine exposure, significant reductions in the
      forebrain were restricted to the bed nucleus of stria terminalis and in the
      brainstem to the nucleus tractus solitarius and dorsomotor nucleus of the vagus
      nerve. The pattern of significantly altered functional activity induced by
      chronic 100-day cocaine self-administration extended within the forebrain to
      include the paraventricular hypothalamic nucleus, and in the brainstem to include
      additional autonomic-related nuclei, the nucleus ambiguus and locus coeruleus.
      These results suggest that even at the initial stages of cocaine self
      administration, functional changes in activity occur in autonomic and reward
      related brain regions. These alterations progress with prolonged cocaine
      exposure, and therefore may be involved in mediating changes in central autonomic
      control and the neuroadaptations reported to result from chronic drug abuse.

PMID- 15488324
TI  - MR perfusion-weighted imaging and quantitative analysis of cerebral hemodynamics
      with symptom provocation in unmedicated patients with obsessive-compulsive
      disorder.
AB  - We evaluated the potential effectiveness of dynamic contrast-enhanced perfusion
      weighted images (PWI) in determining hemodynamic activation in brain structures
      that may be involved in mediating the symptomatology of patients with obsessive
      compulsive disorder (OCD), as manifested by contamination obsessions with washing
      compulsions. Ten unmedicated female patients with OCD were subjected to PWI, and
      relative cerebral blood flow (rCBF) in each region of interest (ROI) and self
      ratings of OCD symptoms were compared before and after symptom provocation. We
      found that increases in the Anxiety Analogue Scale (AAS) and OCD Analogue Scale
      (OCDAS) scores were each significantly associated with provocation. The
      correlations between OCDAS and AAS scores were also statistically significant
      during both the control and provoked conditions. Compared with the control state,
      there was a significant increase in rCBF during the symptomatic state in the
      right head of caudate nucleus, thalamus, and bilateral orbitofrontal cortices
      (OFC). No statistical changes in rCBF were found in the bilateral anterior
      cingulate cortices (ACC). These findings demonstrate that OCD symptomatology is
      accompanied by anxiety, and that abnormal features are particularly apparent in
      the orbitofrontal-subcortical circuits.

PMID- 15488325
TI  - Simvastatin induces proliferation inhibition and apoptosis in C6 glioma cells via
      c-jun N-terminal kinase.
AB  - The lipid-lowering drugs, statins, induce apoptosis in a variety of tumor cells.
      Here we investigated the apoptotic effect of the lipophilic statin, simvastatin,
      in C6 glioma cells and the underlying effects on intracellular signal
      transduction. Simvastatin inhibited cell proliferation totally after 20h of
      treatment as shown by the decrease in proliferating cell nuclear antigen
      expression in the nucleus. Subsequently, simvastatin caused apoptotic cell death
      by shrinkage of cytoplasm and condensation of chromatin, and DNA fragmentation.
      The features of apoptosis were visible only after 48 h of treatment, possibly
      reflecting a requirement for cell commitment to growth arrest. In
      immunocytochemical and immunoblotting experiments we have shown that simvastatin
      markedly increased the phosphorylation of ATF-2 and c-jun in the nucleus of the
      C6 glioma cells at early time points which was preserved even 24 h after
      treatment. In contrast, activities of protein kinases Erk1/2 and AKT in the cell
      survival pathway remained unchanged throughout the treatment. Selective inhibitor
      of JNK, but not p38 kinase, reduced simvastatin-induced cell death and ATF-2 and
      c-jun phosphorylation suggesting that JNK-dependent activation of ATF-2 and c-jun
      may play an important role in simvastatin-induced proliferation inhibition and
      apoptosis in C6 glioma cells. These observations suggest that statins may have
      clinical significance in the prevention of glial tumors beyond their cholesterol
      lowering effect and JNK may be a rational target for sensitizing glioma cells to
      chemotherapeutic agents.

PMID- 15488326
TI  - Immunization of Alzheimer model mice with adenovirus vectors encoding amyloid
      beta-protein and GM-CSF reduces amyloid load in the brain.
AB  - Induction of anti-amyloid beta-protein (Abeta) antibodies in transgenic mouse
      models of Alzheimer disease (AD) by repeated injection of synthetic Abeta was
      shown to be effective in preventing and removing deposition of Abeta aggregates
      in the brain. Here, we have tested a non-invasive modality whereby a replication
      defective adenovirus vector encoding Abeta was intranasally administered to mice
      to elicit immune responses against Abeta. Intranasal immunization only with the
      adenovirus vector failed to induce significant immune responses. When an
      adenovirus vector encoding granulocyte/macrophage-colony stimulating factor (GM
      CSF) was used as an adjuvant in conjunction with the adenovirus encoding Abeta, a
      marked immune response was elicited against Abeta. Immunoglobulin isotyping
      revealed that the induced anti-Abeta antibodies are predominantly of the IgG2b
      and IgG1 isotypes, suggesting a Th-2 anti-inflammatory type. Furthermore, amyloid
      load in the brain of AD model mice (Tg2576) vaccinated with adenovirus vectors
      encoding Abeta and GM-CSF was much smaller than that in control Tg2576 mice.
      Thus, intranasal administration of adenovirus vectors encoding Abeta and GM-CSF
      may be effective in prevention and treatment of AD.

PMID- 15488327
TI  - The augmentation of brain thioredoxin-1 expression after severe hypobaric hypoxia
      by the preconditioning in rats.
AB  - Induction of endogenous antioxidants is one of the key molecular mechanisms of
      cell resistance to hypoxia/ischemia. The effect of severe hypoxia on the
      expression of cytosolic antioxidant thioredoxin-1 (Trx) in hippocampus and
      neocortex was studied in preconditioned and non-preconditioned rats. The
      preconditioning consisted of three trials of mild hypobaric hypoxia (360 Torr, 2
      h) spaced at 24 h. Twenty-four hours after the last trial rats were subjected to
      severe hypobaric hypoxia (180 Torr, 3 h). Trx expression was studied by
      immunocytochemistry. In hippocampus severe hypobaric hypoxia rapidly induced Trx
      expression, which remained elevated still at 24 h. In neocortex the enhanced
      expression appeared only at 24 h. The preconditioning significantly augmented
      severe hypoxia-induced Trx-immunoreactivity at 3 h but not at 24 h. These
      findings point out that Trx contributes to mechanisms of brain tolerance to
      hypobaric hypoxia, especially in early periods after the exposure.

PMID- 15488328
TI  - In vitro differentiated neural stem cells express functional glial glutamate
      transporters.
AB  - The possibility to isolate stem cells from the adult central nervous system and
      to maintain and propagate these cells in vitro has raised a general interest with
      regards to their use in cell replacement therapy for degenerative brain diseases.
      Considering the critical role played by astrocytes in the control of glutamate
      homeostasis, we have characterised the expression of functional glutamate
      transporters in neural stem cells exposed to selected culture conditions
      favouring their differentiation into astrocytes. Commonly, neural stem cells
      proliferate in suspension as neurospheres in serum-free medium. The addition of
      serum or a supplement of growth factors (G5) to the culture medium was found to
      trigger cell adhesion on coated surfaces and to favour their differentiation.
      Indeed, after 7 days in these conditions, the vast majority of the cells adopted
      markedly distinct morphologies corresponding to protoplasmic (with serum) or
      fibrous (with G5 supplement) astrocytes and approximately 35-40% acquired the
      expression of the glial fibrillary acidic protein (GFAP). Immunocytochemical
      analysis also revealed that the treatments with serum or with the G5 supplement
      triggered the expression of the glial glutamate transporters GLT-1 (35 and 21%,
      respectively) and GLAST (29 and 69%, respectively). This effect was correlated
      with a robust increase in the Na+ -dependent [3H]-d-aspartate uptake, which was
      partially inhibited by dihydrokainate, a selective blocker of GLT-1. Together,
      these results indicate that in vitro differentiation of cultured neural stem
      cells can give rise to distinct populations of astrocytes expressing functional
      glutamate transporters.

PMID- 15488329
TI  - The monosodium iodoacetate model of osteoarthritis: a model of chronic
      nociceptive pain in rats?
AB  - Osteoarthritis (OA) is a widespread condition affecting the elderly population.
      One of the most prominent features but least studied symptoms is chronic pain
      associated with OA. The study objective was to determine pain endpoints in rats
      with monosodium iodoacetate (MIA) induced OA, and to investigate the efficacy of
      common nociceptive agents. Sprague-Dawley rats received an intraarticular
      injection of either 25 microl 80 mg/ml MIA or 25 microl 0.9% sterile saline into
      the right knee joint. Changes in von Frey thresholds and latencies to stroking
      with a cotton bud (punctate and dynamic allodynia, respectively) were measured
      pre- and for up to 10 weeks post-intraarticular injection. Changes in hind paw
      weight distribution were also determined. Both punctate allodynia and a weight
      bearing deficit were observed in MIA-treated rats for up to 10 weeks.
      Interestingly, dynamic allodynia was not detected at any time point tested.
      Morphine (0.3-3 mg/kg, s.c.) and tramadol (3-100 mg/kg, p.o.) dose-dependently
      inhibited punctate allodynia and partially reversed weight bearing deficit. In
      conclusion, the MIA model of OA is reproducible and mimics OA pain in humans.
      Analgesic drug studies indicate this model may be useful for investigating
      chronic nociceptive pain.

PMID- 15488330
TI  - Familial Alzheimer disease associated with A713T mutation in APP.
AB  - Mutations in APP are associated with familial early-onset Alzheimer disease
      (FAD). Examination of the genomic sequence in one patient with FAD revealed a
      change located in the axon 17 of the APP gene at position 275329G>A (GenBank
      accession number: D87675; GI: 2429080); cDNA sequence 2137G>A (GenBank accession
      number: X06989; GI: 28720). This corresponds to the mutation A713T in APP. AD
      stage VI of neurofibrillary degeneration and stage C of Abeta-amyloid burden was
      found at the post-mortem neuropathological examination. Previous studies have
      suggested that the mutation A713T in APP is a silent mutation or polymorphism.
      However, we have not found this change in APP in a control population analyzed by
      the amplification-refractory mutation system (ARMS). It is concluded that A713T
      in APP is implicated in the pathogenesis of AD. Since the immunohistochemical
      study indicates that A713T mutation is not likely to relate with Abeta-amyloid
      processing, the causative role of this rare mutation remains to be warranted.

PMID- 15488331
TI  - Protective effect of nicotine on tunicamycin-induced apoptosis of PC12h cells.
AB  - Nicotine has been reported to have neuroprotective effects. The present study
      deals with the neuroprotective effect of nicotine on the tunicamycin-induced
      apoptosis of PC12h cells. Treatment of PC12h cells with tunicamycin causes
      endoplasmic reticulum stress leading to apoptosis. Nicotine dose-dependently
      prevented the tunicamycin-induced apoptosis. Hoechst 33258 staining demonstrated
      the protective effect of nicotine against tunicamycin-induced apoptosis.
      Treatment with nicotinic acetylcholine receptor (nAChR) and L-type voltage
      sensitive calcium channel (L-VSCC) antagonists prevented the nicotine-induced
      protective effect. A phosphatidylinositol 3-kinase (PI3-K) inhibitor had no
      influence on the nicotine-induced neuroprotective effect. These results show that
      the neuroprotective effect of nicotine occurs through nAChRs including the alpha
      7 subtype and L-VSCC in PC12h cells and not through the PI3-K/Akt pathway.

PMID- 15488332
TI  - NMDA receptor-dependent long-term potentiation in the telencephalon of the
      zebrafish.
AB  - In Mg2+ -free aCSF, bursting discharges were induced in the posterior
      telencephalon of zebrafish following an electrical stimulation of the anterior
      telencephalon. The bursting discharges were partially reduced by CNQX (10
      microM), an AMPA receptor antagonist, and the remaining activity was completely
      blocked by an additional treatment of APV (50 microM), an NMDA receptor
      antagonist. Long-term potentiation that lasted more than 1 h was also induced
      after 20 min of perfusion with KCl (10 mM). The degree of KCl-induced long-term
      potentiation (K-LTP) was reduced when a concomitant electrical stimulation was
      not delivered during a KCl perfusion. K-LTP was blocked by APV (50 microM) but
      not by nifedipine (1 microM), an L-type Ca2+ channel blocker. Furthermore, K-LTP
      was not induced in the presence of a broad spectrum inhibitor for protein
      kinases, H-7 (10 microM). These results suggest that NMDA receptors and protein
      kinases play important roles in the synaptic plasticity of the zebrafish brain.

PMID- 15488333
TI  - PACAP deficient mice display reduced carbohydrate intake and PACAP activates NPY
      containing neurons in the rat hypothalamic arcuate nucleus.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) potentiates both
      insulin release from islets and insulin action in adipocytes. Therefore, this
      peptide is considered a regulator of glucose homeostasis. PACAP and its receptors
      are localized not only in the peripheral tissues but in the central nervous
      system. The present study examined whether PACAP regulates the feeding behavior
      and the activity of neurons in the hypothalamic arcuate nucleus (ARC), a feeding
      center. Food intake was measured in the PACAP knock-out mice. Cytosolic Ca2+
      concentration ([Ca2+]i) in single neurons isolated from the ARC of rats was
      measured by fura-2 microfluorometry, followed by immunocytochemical staining with
      anti-NPY antiserum. PACAP knock-out mice showed a decrease in the intake of high
      carbohydrate, but not high fat, food. PACAP increased [Ca2+]i in NPY neurons of
      the ARC that are implicated in the feeding, particularly the carbohydrate
      ingestion. Agonists of PACAP receptors, PAC1-R and VPAC2-R, also increased
      [Ca2+]i. The present study, by demonstrating that PACAP directly reacts with the
      ARC NPY neurons to increase [Ca2+]i and that ingestion of the carbohydrate-rich
      food is reduced in PACAP-deficiency, suggests a facilitative role for PACAP in
      the carbohydrate intake.

PMID- 15488334
TI  - Impairment of olfactory discrimination by blockade of nitric oxide activity in
      the terrestrial slug Limax valentianus.
AB  - The terrestrial slug Limax readily associates an innately preferred food odor
      with the aversive taste of quinidine. We investigated slugs' olfactory
      discrimination capability among structurally similar alcohols and the effects of
      inhibition of nitric oxide (NO) synthesis to the olfactory discrimination
      behavior, using an olfactory discriminatory learning task. Limax could
      discriminate among the odor of 1-octanol (OT), 3-methylcyclohexanol (MC) and 1
      hexanol (HX). OT was perceptually more similar to HX than was MC for them. When
      NO synthesis was inhibited by injecting N-nitro-L-arginine methyl ester (l-NAME)
      shortly before the discrimination test, slugs could not discriminate between OT
      and HX whereas the retrieval of olfactory memory and the discrimination between
      OT and MC remained intact. These results indicate that the NO cascade plays a
      crucial role for fine olfactory discrimination in Limax.

PMID- 15488335
TI  - Social behavioural profile of cocaine in isolated and grouped male mice.
AB  - Studies concerning the relationship between cocaine and aggression in humans as
      well as in animals have discrepant outcomes. Increases, decreases, or no changes,
      have been reported after single or chronic cocaine administration in animal
      models. To clarify, at least in part, the complex behavioural actions of cocaine,
      the present study evaluated cocaine effects on social behaviours of mice exposed
      to different situations (isolated or group housed) using confrontations between
      two male mice in a neutral area. Different doses of cocaine (6, 25 and 50 mg/kg)
      were administered in a single or binge pattern (three doses in 24 h) and the
      behavioural test was performed 20 min after the last injection. No increases in
      aggression were observed in any situation tested. Instead, cocaine at the two
      higher doses employed (either in single or binge administration), decreased
      aggressive behaviours in isolated mice, with no changes being observed in grouped
      animals. In both types of animals, cocaine increased defensive elements
      (avoidance/flee) and abolishes social contacts. In conclusion, cocaine presents
      an anti-aggressive action and may be interpreted as having an anxiogenic-like
      effect.

PMID- 15488336
TI  - Relation between cognitive distortions and neurobehavior disinhibition on the
      development of substance use during adolescence and substance use disorder by
      young adulthood: a prospective study.
AB  - OBJECTIVE: Previous research has demonstrated that neurobehavior disinhibition
      increases the risk for a diagnosis of substance use disorder (SUD). This
      investigation tested the hypothesis that a deficiency in the capacity to appraise
      the effects of alcohol and drugs and interpret social interactions mediates the
      relation between neurobehavior disinhibition in childhood and SUD by early
      adulthood. METHODS: Boys with fathers having lifetime SUD (N=88) and no SUD or
      other psychiatric disorder (N=127) were prospectively tracked from ages 10-12 to
      19 years. Neurobehavior disinhibition was evaluated at baseline followed by
      assessments of cognitive distortions and substance use involvement in early and
      mid-adolescence. SUD outcome was evaluated up to age 19 years. RESULTS: Cognitive
      distortions (age 12-14 years) mediated the association between neurobehavior
      disinhibition (age 10-12 years) and marijuana use (age 16 years) which, in turn,
      predicted SUD by age 19 years. Cognitive distortions in early adolescence did not
      directly predict SUD by young adulthood. CONCLUSIONS: Inaccurate social
      cognition, significantly predicted by childhood neurobehavior disinhibition,
      biases development toward marijuana use prodromal to SUD. These results indicate
      that cognitive processes, in conjunction with psychological self-regulation,
      comprise important components of the individual liability to SUD.

PMID- 15488337
TI  - Accuracy of alcohol diagnosis among DWI offenders referred for screening.
AB  - BACKGROUND: Most US courts use screening programs to evaluate substance-abuse
      problems of convicted driving while impaired (DWI) offenders. Typically self
      report information determines need for treatment. However, little is known about
      the accuracy of self-reports of alcohol-use problems in this population. METHODS:
      DSM-III-R alcohol abuse and dependence diagnoses from an initial, court-ordered
      screening evaluation of 583 female and 495 male convicted DWI offenders were
      compared with diagnoses and other self-reported information from a voluntary,
      noncoerced interview 5 years after the screening referral. RESULTS: At initial
      screening, 16.8% of offenders were diagnosed with alcohol abuse and 20.1% with
      alcohol dependence. At the 5-year interview, 19.9 and 60.1% received a
      retrospective diagnosis of alcohol abuse or dependence at the age at which they
      were screened. Significantly fewer of those with a retrospective alcohol
      diagnosis reported that their alcohol use self-reports at screening were "very
      accurate" compared to those with no retrospective diagnosis. CONCLUSIONS:
      Although many DWI offenders undergoing screening have diagnosable alcohol-related
      problems, underreporting is common, leading to inaccurate diagnosis and,
      therefore, a missed treatment opportunity. The research community and
      policymakers should review and reform the current screening system for alcohol
      impaired drivers to better address this serious public health problem.

PMID- 15488338
TI  - Depressed smokers and stage of change: implications for treatment interventions.
AB  - Tobacco Dependence among smokers with psychiatric disorders has been under
      addressed by the mental health, addictions, and tobacco control communities. This
      study examined depressed smokers' readiness to quit and the applicability of the
      Stages of Change framework to a psychiatric sample. Currently depressed smokers
      (N=322) were recruited from four outpatient psychiatric clinics. Participants
      averaged 16 cigarettes per day (S.D.=10) and 24 years (S.D.=13) of smoking. The
      majority (79%) reported intention to quit smoking with 24% ready to take action
      in the next 30 days. Individuals in the preparation stage reported more prior
      quit attempts, a greater commitment to abstinence, increased recognition of the
      cons of smoking, and greater use of the processes of change. Precontemplators
      were least likely to identify a goal related to their smoking behavior.
      Depressive symptom severity and history of recurrent depressive episodes were
      unrelated to readiness to quit. This study is one of the first to examine the
      smoking behaviors of currently depressed psychiatric outpatients. The level and
      longevity of their tobacco use underscore the need for cessation interventions.
      The consistency in hypothesized patterns among theoretical constructs of the
      Stages of Change model supports the transfer of stage-tailored interventions to
      this clinical population.

PMID- 15488339
TI  - Patterns of cigarette smoking among students from 19 colleges and universities in
      Jiangsu Province, China: a latent class analysis.
AB  - Entrance into college may be associated with elevated risk of progression in
      cigarette use among Chinese students. The purpose of this study was to examine
      patterns and dynamics of cigarette smoking by age and grade among college
      students in China. Cross-sectional data from 1845 students (44% females) in 19
      colleges and universities in Jiangsu Province were derived from the Chinese Youth
      Health Risk Behavior Survey in 2001. Data were analyzed using latent class
      analysis (LCA). Overall 11 mutually exclusive types (latent classes) of cigarette
      users were derived and their proportions estimated from four variables: lifetime
      smoking, past 30-day smoking, attempting to quit in the past, and intention to
      smoke in the future. Two types (resistant never-smokers, self-stopped resistant
      nonsmokers) were observed across age groups and grades for both males and females
      while other smoking types varied with gender, age and grade. Advanced cigarette
      smoking types appeared in older age groups and higher grades. The cross-sectional
      age and grade trend suggests substantial progression in cigarette smoking among
      Chinese college students, underscoring the need for prevention among these
      students. Results also suggest that LCA may be an effective methodology for
      analyzing behavioral types and their dynamics with a limited number of variables.

PMID- 15488340
TI  - The Addiction Severity Index medical and psychiatric composite scores measure
      similar domains as the SF-36 in substance-dependent veterans: concurrent and
      discriminant validity.
AB  - BACKGROUND: Recently attention has focused on the assessment of functional health
      status in substance-dependent individuals. The addiction severity index (ASI) is
      a widely used assessment instrument that includes scales to reflect current
      medical and psychiatric status. This study examines the concurrent validity of
      these ASI composite scores in relation to the short form 36-item health survey
      (SF-36), a well-established measure of health-related quality of life/functional
      health status. METHODS: Veterans (n=674) were assessed at admission to substance
      dependence treatment. Correlations were performed between ASI composite scores
      and SF-36 scales and the physical and mental summary components (PSC and MSC,
      respectively). Areas under receiver operating characteristic (ROC) curves
      determined the descriminative ability of the ASI composites to ascertain
      impairment. RESULTS: The ASI medical composite score demonstrated robust
      correlations with the four SF-36 scales that relate to physical health and with
      the PCS. The ASI psychiatric composite score had robust correlations with the
      four SF-36 scales related to mental health and with the mental component summary
      (MCS). ROC curves indicated that the ASI medical (AUC=0.83) and psychiatric
      composites (AUC=0.90) accurately detected subjects with impairment. CONCLUSIONS:
      ASI medical and psychiatric composite scores provide effective initial screening
      for patients with impaired functional status as measured by the corresponding SF
      36 component summary scores.

PMID- 15488341
TI  - Oral methylphenidate challenge selectively decreases putaminal T2 in healthy
      subjects.
AB  - Despite the recent rise in oral methylphenidate (MPH) abuse, few studies have
      characterized the time course of oral MPH brain effects in human subjects.
      Accordingly, this study assessed the hemodynamic effects of oral MPH effects in
      11 healthy young adults (six women), by measuring brain transverse relaxation
      times (T2). T2 can be interpreted as a surrogate marker for, and inversely
      correlated with, steady-state cerebral blood volume (CBV). Data were acquired
      from the caudate nucleus, putamen, and thalamus, using a 1.5 T MRI scanner at
      baseline and serially for 2 h following oral MPH administration (0.5 mg/kg).
      Physiological and subjective measures and plasma MPH levels also were examined.
      MPH induced a selective T2 decrease (-1.65+/-0.53 ms) in the putamen
      (F(6,54)=2.68, P<0.03). Heartrate, blood pressure and plasma MPH levels increased
      significantly after drug administration, as well as subjective ratings of
      "feeling drug effect". T2 decreases may reflect MPH-induced increases in
      putaminal blood volume. These data suggest that T2 relaxometry can be used to
      study the time course of regional cerebral blood volume responses to MPH and
      perhaps to other stimulant drugs.

PMID- 15488342
TI  - Neurocognitive performance of methamphetamine users discordant for history of
      marijuana exposure.
AB  - Abuse of the stimulant drug methamphetamine is associated with neural injury and
      neuropsychological (NP) deficits, while the residual effects of marijuana use
      remain uncertain. We sought to determine if methamphetamine dependent persons who
      also met criteria for marijuana abuse or dependence evidenced different NP
      performance than those with dependence for methamphetamine alone. We examined
      three groups that did not differ significantly on important demographic factors:
      (1) subjects with a history of methamphetamine dependence and history of
      marijuana abuse/dependence (METH+/MJ+, n=27); (2) methamphetamine dependent
      subjects without history of marijuana abuse/dependence (METH+/MJ-, n=26); (3) a
      control group with minimal or no drug use (n=41). A comprehensive NP battery was
      administered and performance was quantified for five cognitive ability areas. The
      METH+/MJ- group generally demonstrated the greatest NP impairment, with
      statistically significant differences observed between the METH+/MJ- and control
      group in learning, retention/retrieval, and a summary score of global NP
      performance. The METH+/MJ+ group did not differ significantly from the control or
      METH+/MJ- group on any NP ability. However, there was a significant linear trend
      in the global NP score suggesting that the METH+/MJ+ performed intermediate to
      the control and METH+/MJ- groups. Based on these findings, we cannot conclude
      that there is a protective effect of marijuana use in methamphetamine users;
      however, marijuana use clearly did not appear to exacerbate methamphetamine
      neurotoxicity. Further investigations are needed to determine if the emerging
      literature, suggesting that certain cannabinoids might have neuroprotective
      actions, is generalizable to community-dwelling substance abusers.

PMID- 15488343
TI  - Reinforcing and subjective effects of the volatile anesthetic, sevoflurane.
AB  - Sevoflurane is a volatile anesthetic that is chemically similar to volatile
      substances of abuse and can be safely administered to humans in laboratory
      research. In this study, the reinforcing and subjective effects of five
      concentrations of sevoflurane (0, 0.2, 0.4, 0.6, 0.8% sevoflurane in O2) were
      studied in 20 non-drug-abusers. During each of five sessions, subjects sampled a
      concentration of sevoflurane and 100% O2 (placebo) for 10 min each. Later, within
      the session, they chose nine times, once every 5 min, among sevoflurane (e.g.
      "Agent A"), placebo (e.g. "Agent B"), or neither (and were administered 100% O2,
      identified as "drug-free air"). Although "neither" was selected most frequently,
      mean preference ratios (sevoflurane choices/[sevoflurane choices+placebo
      choices]) and total sevoflurane choice peaked at the 0.4% concentration. Choice
      patterns varied across subjects, with some subjects never choosing sevoflurane
      and other subjects showing monotonic increasing or bitonic concentration-choice
      functions. Concentration-related increases in subjective effects were observed,
      including effects that are putatively associated with abuse liability. Ratings of
      drug liking and of wanting to inhale the drug again were positively correlated
      with sevoflurane choice. This study shows that sevoflurane can function as a
      reinforcer and produce abuse liability-related subjective effects in some healthy
      volunteers.

PMID- 15488344
TI  - A comparison of injection and non-injection methamphetamine-using HIV positive
      men who have sex with men.
AB  - There is a paucity of research on the psychosocial and behavioral characteristics
      of individuals who inject methamphetamine (meth). The present study compared
      injection and non-injection users of meth in terms of background characteristics,
      drug use patterns, health and social problems, sexual risk behavior, and
      psychosocial factors. The sample consisted of 194 HIV+Men who have Sex with Men
      (MSM) who were enrolled in a sexual risk reduction intervention for meth users.
      Men who injected meth were significantly more likely to be Caucasian, bisexual,
      homeless, divorced/separated, with lower educational attainment as compared to
      non-injectors. Injectors also reported more years of meth use, greater frequency
      and amount of meth use, more social and health problems, including higher
      prevalence of STDs and Hepatitis C, and more sexual risk behaviors. In terms of
      psychosocial factors, injection users of meth scored significantly higher on
      measures of impulsivity and experiences of rejection, and lower on a measure of
      emotional support. A multivariate logistic regression revealed that educational
      attainment and experiences of rejection were the factors that best discriminated
      between injection and non-injection users of meth. The unique characteristics of
      injection meth users are discussed in relation to the development of effective
      HIV prevention programs for the target population.

PMID- 15488345
TI  - Substance use histories in patients seeking treatment for controlled-release
      oxycodone dependence.
AB  - The characteristics of patients currently abusing controlled-release (CR)
      oxycodone admitted for inpatient detoxification were ascertained from medical
      record review of 48 inpatients with CR oxycodone dependence. Patients were
      categorized according to the manner in which they initially received the drug:
      illicitly or by prescription for legitimate medical use. Fifteen of the 48
      patients (31%) initially obtained a CR oxycodone prescription legitimately for a
      medical condition. While none of these 15 patients had a history of prior opioid
      misuse, they were more likely than illicit CR oxycodone users to report prior
      detoxifications (P<0.03) as well as a lower mean age of first alcohol use
      (legitimate=11.7 versus illicit=14.7, P<0.05) and first illicit drug use
      (legitimate=12.8 versus illicit=15.8, P<0.05). These findings suggest that a
      history of substance abuse is common among patients abusing CR oxycodone,
      including individuals for whom CR oxycodone was initially legitimately prescribed
      for pain.

PMID- 15488346
TI  - Tibolone and its metabolites acutely relax rabbit coronary arteries in vitro.
AB  - OBJECTIVES: To compare the acute effects of estradiol, tibolone and its
      metabolites on coronary arteries in vitro and to investigate possible vascular
      mechanisms. METHODS: Coronary artery ring segments from female rabbits were
      mounted in myographs for isometric tension recordings. Concentration-response
      curves to tibolone, 3 alpha-OH-tibolone, 3 beta-OH-tibolone, Delta 4-isomer and
      17 beta-estradiol were obtained after precontraction with potassium 30 mmol/l and
      after addition of N omega-nitro-l-arginine methyl ester 10(-4) mol/l (l-NAME, an
      inhibitor of endothelial nitric oxide (NO) synthase) or tetraethylammonium
      chloride 10(-2) mol/l (TEA, an unspecific inhibitor of potassium channels). The
      effects of the different substances to calcium concentration-response curves were
      evaluated. Responses are expressed as maximal contraction (E max), concentration
      giving half maximal contraction (log EC50) or area under curve (AUC). RESULTS:
      Tibolone and its metabolites induced a concentration-dependent vasodilatation
      comparable to that of 17 beta-estradiol with the rank of potency: 3 beta-OH
      tibolone approximately = to tibolone>3 alpha-OH-tibolone>Delta 4-isomer (ANOVA).
      l-NAME partly inhibited the relaxation to all substances. TEA induced a slight
      rightward shift of the relaxation to 3 alpha-OH-tibolone (log EC50: -5.05 versus 
      5.20; P<0.05; Student's t-test), but not to the other substances. Calcium
      concentration-dependent contraction curves were inhibited by all substances
      compared to controls (AUC, P<0.05, ANOVA). CONCLUSIONS: Our data indicate that
      the acute relaxation induced by tibolone and its metabolites in coronary arteries
      in vitro are probably mediated by endothelium independent inhibition of calcium
      channels but may also involve an endothelium-dependent mechanism via nitric
      oxide. The effect of tibolone is comparable to that of 17 beta-estradiol in this
      set-up.

PMID- 15488347
TI  - Effect of hormone therapy on BP in normotensive and hypertensive postmenopausal
      women.
AB  - High blood pressure (BP) ranks as the greatest risk factor for cardiovascular
      disease. The increased cardiovascular risk determined in recent interventional
      studies has led the health authorities in some countries to re-ignite the
      discussion about whether hypertension should be listed as a contraindication for
      hormone replacement therapy (HRT). We reviewed papers published since 1960 and
      listed in MEDLINE, EMBASE and Biosis, on studies that monitored the course of BP
      during HRT. We found that both primarily normotensive and hypertensive
      postmenopausal women actually run only a very low risk of BP increase during HRT,
      indeed, BP was often lowered. In one of our own studies 1397 hypertensive women
      with BP diastolic >95 mmHg received transdermal HRT regimens; BP was lowered by
      an average of 7 mmHg systolic and 9 mmHg diastolic. The results of the more
      recent 24-h ambulatory BP studies are particularly conclusive. At least 19 such
      studies have been performed, 13 placebo-controlled and 10 cross-over; 5 found no
      effect on BP and 14 studies demonstrated BP reductions. BP was lowered by
      treatment with transdermal estradiol in 11 of 13 studies and by oral estrogen in
      4 of 11 studies. The effects were not consistent with regard to systolic or
      diastolic BP nor to action on day- and night-time BP. It cannot be ruled out that
      some women with a particular predisposition exhibit an abnormal reaction to the
      vasoactive effects of HRT, and there is a paucity of long-term data on risk
      populations, specifically on the progestogenic effects in patients with pre
      existing arteriosclerotic lesions. In conclusion, the risk of developing
      hypertension during HRT is very low, but hormone therapy should always be
      appropriately indicated and during therapy BP should be checked regularly.

PMID- 15488348
TI  - Relationship between psychological complaints and vasomotor symptoms during
      climacteric.
AB  - BACKGROUND: It has been suggested that hormonal changes and environmental
      alterations during the climacteric period are important in the development of
      psychological symptoms. OBJECTIVE: To evaluate the role of biological and psycho
      social factors in the prevalence of climacteric symptoms. DESIGN: Open, cross
      sectional, observational and descriptive study. MATERIAL AND METHODS: A total of
      300 women between 40 and 59 years of age were evaluated using Greene scale for
      climacteric symptoms, Cooper questionnaire for psychosomatic symptoms of stress,
      Smilkstein family apgar for family dysfunction, Duke-UNC questionnaire for social
      support and Israel scale for vital events. All these tests have been previously
      validated in Spanish. RESULTS: Postmenopausal women do not have higher prevalence
      of psychological symptoms, they only have more vasomotor symptoms. Premenopausal
      women with vasomotor symptoms have more psychological and somatic symptoms and
      stress, independently of the vital events, family dysfunction or poor social
      support. Vasomotor symptoms in the premenopause are associated with increased
      risk of anxiety (OR: 3.7, IC: 1.4-9.7; P<0.008), depression (OR: 8.1, IC: 2.5
      26.4; P<0.0005), somatic symptoms (OR: 14.9, IC: 3.4-65.3; P<0.0003), sexual
      dysfunction (OR: 7.2, IC: 2.5-20.6; P<0.0002) and stress (OR: 7.5, IC: 3.5-15.9;
      P<0.0001). Negative vital events and family dysfunction increase in minor
      intensity the risk of anxiety, depression and stress. CONCLUSION: In conclusion,
      psychological symptoms are frequent in the premenopause and are associated to
      vasomotor symptoms. This observation links psychological symptoms with menopausal
      transition and might suggest an organic base in their origin. The negative psycho
      social environment is a factor that favours the development of these symptoms.

PMID- 15488349
TI  - The age at menopause and associated factors at the health center area in Ankara,
      Turkey.
AB  - OBJECTIVES: This study is performed in one health center area in Ankara, Turkey
      on a women population of 50-65 years in order to demonstrate menopausal status of
      women, age at menopause and factors related with the age at menopause. METHODS:
      This is a cross-sectional study which has been performed on a women population of
      50-65 years. The local population was 17,153 in this area by 2001. All of the
      household determining forms are screened in order to detect the all of the women
      who were in 50-65 years group, then name and addresses of the these women's are
      listed. There were 1089 women aged 50-65 years who were constituting 7% of the
      population. After choosing the first name randomly from the list of the women,
      1/3 systematic sampling method was used and, the number of the women in the
      sampling was 363 (95% C.I., +/-5% S.E.). The response rate among those eligible
      women who were contactable during the study was 99% (360/363). Data were
      collected by interviews through questionnaires. The questionnaire consisted of a
      series of questions concerning age at menopause, socioeconomic status, age at
      menarche, age at first pregnancy, regularity of menstrual cycles, parity,
      duration of breast feeding, use of OCs, BMI, smoking habit, age at menopause of
      the mother and the sister. Chi-square and t-test methods were used for
      statistical analyses. RESULTS: 4.2% of the women were in premenopause, 13.3% were
      in perimenopause, 72.8% were in natural menopause and 9.7% were in surgical
      menopause. Average age at natural menopause was 47+/-4.2 years. Education, age at
      menarche, smoking, age at menopause of the mother and the sister were found to be
      related with the age at menopause. CONCLUSIONS: Ninety-six percent of the women
      over age of 50 years, are at menopause or perimenopause. The results of this
      study suggest that, for factors of genetic and age at menarche, there are not
      many possibilities for the lifestyle changes that would modify age at menopause
      with the subsequent reduction in risk for chronic diseases, but daughters or
      sisters of women with an early menopause and women who smoked or less educated
      could be counselled with respect to family timing.

PMID- 15488350
TI  - The effects of hormone therapy on pulmonary function tests in postmenopausal
      women.
AB  - OBJECTIVE: To investigate the effects of hormone therapy (HT) administered to
      postmenopausal women on pulmonary function tests (PFT). METHODS: Eighty-two
      postmenopausal women who were having natural or surgically initiated menopause
      and had no risk factor that could affect the respiratory system were included
      into this prospective, randomized study. Twenty-five women who refused to use HT
      were assessed as the control group (Group I). Nineteen women who accepted using
      HT and who were having surgically initiated menopause were given continuous
      estrogen (Group II), 23 were given continuous estrogen and progesterone in
      combination (Group III) and 15 were given cyclic estrogen and progesterone
      combination (Group IV). Forced expiratory volume (FEV1), forced vital capacity
      (FVC), FEV1/FVC, forced expiratory flow rate over 25-75% of the forced vital
      capacity volume and peak expiratory flow rate were assessed at the beginning of
      the treatment and in the third month in order to evaluate the effects of HT
      regimens on the women's PFT. RESULTS: A statistically significant increase was
      observed only in the FEV1 and FVC parameters of Group III after three months of
      therapy (P<0.05). The comparison between pre- and posttherapy FEV1 and FVC values
      showed an increase in the Group IV, but the difference was not statistically
      significant, while there was no difference between basal and third month FEV1 and
      FVC values of the group receiving estrogen only. CONCLUSIONS: It was seen that
      particularly continuous combined HT regimen positively affected the FEV1 and FVC
      parameters of the postmenopausal women.

PMID- 15488351
TI  - Immunohistochemical expression of estrogen and progesterone receptors in
      endometrial polyps and adjacent endometrium in postmenopausal women.
AB  - OBJECTIVE: To detect the presence of estrogen (ER) and progesterone (PR)
      receptors in endometrial polyps and adjacent endometrium in postmenopausal women.
      METHODS: Forty-four consecutively enrolled postmenopausal patients were submitted
      to operative hysteroscopy. These patients had diagnosed benign endometrial polyp.
      The presence of ER and PR was determined in endometrial samples and polyps by
      immunohistochemical method and the slides were evaluated using a semiquantitative
      analysis. RESULTS: In the glandular epithelium, the median of the ER score was
      7.0 in the polyps and 5.0 in the endometrium (P<0.0001) and the median of the PR
      was 6.0 in the polyps and 4.0 in the endometrium (P<0.0001). In the stroma, the
      median of the ER score was 6.0 in the polyps and 5.0 in the endometrium (P=0.021)
      and the median of the PR score was 4.0 in the polyps and 4.5 in the endometrium
      (P=0.34 ). CONCLUSIONS: Our data suggests that steroids receptors present a
      crucial role in the phisiopathology of the endometrial polyps in postmenopausal
      women, specially the estrogen receptors.

PMID- 15488352
TI  - Breast cancer risk during HRT: influence of estradiol metabolites on breast
      cancer and endothelial cell proliferation.
AB  - OBJECTIVES: Long-term hormone replacement therapy is associated with an increased
      breast cancer risk. Evidence is accumulating that estradiol metabolites are
      involved in carcinogenesis. These metabolites may have proliferating and anti
      proliferative properties. We have investigated the effect of 14 metabolites on
      the proliferation of human breast cancer cells and on the proliferation of human
      vascular endothelial cells. METHODS: As cell model, human umbilical vein
      endothelial cells (HUVEC) and the human breast cancer cell line MCF-7 were used.
      The relationship between dosage and effect was tested over the pharmacological
      concentration range of 10(-8) to 10(-5) M. RESULTS: In HUVECs, all of 10 A-ring
      metabolites tested stimulated the growth of the endothelial cells at the lower
      concentrations. At the highest concentration, some A-ring metabolites caused
      significant inhibitions. The D-ring metabolites showed no marked effects compared
      to the A-ring metabolites. In MCF-7 cells also, nearly all A-ring metabolites
      demonstrated a biphasic reaction behaviour on cell proliferation. For the D-ring
      metabolites, this biphasic pattern was only found for 16 alpha-hydroxyestrone,
      but the inhibitory effect of this metabolite was weak. CONCLUSION: These results
      indicate that certain endogenous estradiol metabolites are able to stimulate
      breast cancer cell proliferation, and others may be suitable for breast cancer
      treatment when used in high dosages, since they inhibit cancer cell growth as
      well as neoangiogensis. This may be of special importance for therapy, since some
      of these metabolites are virtually devoid of any oestrogenic activity.

PMID- 15488353
TI  - Use of hormone replacement therapy in Italian women aged 50-70 years.
AB  - OBJECTIVES: The aim of the present cross-sectional analysis was to describe
      patterns and determinants of use of hormone replacement therapy (HRT) in a large
      sample of women attending mammographic screening. METHODS: Between 1999 and 2001,
      8533 women aged 50-70 years were recruited by 11 screening centres, and
      structured interviews were made collecting information on socio-demographic
      characteristics, lifestyle habits, medical and reproductive history (overall
      response rate 87%). RESULTS: Current HRT use was reported by 6.9% of women
      (n=585), the average duration of use being 3.5 years; 13.2% were ever HRT users.
      Binomial and multinomial logistic regression (MLR) analyses showed that younger
      age, higher educational level, past mammographic examination and history of
      bilateral oophorectomy were the major predictors of current and ever HRT use.
      Current use was also more frequently reported by women who were thinner,
      nulliparae, had had induced menopause, had a later onset of menopause, with
      history of oral contraceptive use and hysterectomy without bilateral
      oophorectomy. By contrast, those who were diabetics or had positive history of
      cardiovascular disease were less likely to be current HRT users. No differences
      were found in HRT use according to marital status, type of occupation, menopausal
      status, smoking, history of breast cancer, hypercholesterolemia, hypertension and
      phlebitis. CONCLUSIONS: Our results support previous findings indicating that HRT
      use in Italian women is uncommon and of short duration. Current HRT users were
      less likely than non-users to report several characteristics associated with
      higher mortality and morbidity, in accordance with the healthy-user phenomenon
      described in other countries.

PMID- 15488354
TI  - The effects of 17 beta-oestradiol plus dydrogesterone compared with conjugated
      equine oestrogens plus medroxyprogesterone acetate on lipids, apolipoproteins and
      lipoprotein(a).
AB  - OBJECTIVE: To compare the effects of 17 beta-oestradiol plus dydrogesterone with
      conjugated equine oestrogens plus medroxyprogesterone acetate on serum lipids,
      apolipoproteins and lipoprotein(a) in postmenopausal women. METHODS: A multi
      centre, prospective, randomised, double-blind, comparative one-year study in 362
      healthy postmenopausal women aged 39-74 years with an intact uterus. Fasting
      blood samples were taken at baseline and after 28 and 52 weeks of treatment.
      Participants received daily oral treatment with continuous combined 1 mg
      micronised 17 beta-oestradiol/5 mg dydrogesterone (E/D: n=180) or 0.625 mg
      conjugated equine oestrogens/5 mg medroxyprogesterone acetate (CEE/MPA: n=182).
      RESULTS: Significant differences between the two groups after 52 weeks were
      observed for total cholesterol (E/D: -1.7%; CEE/MPA: -7.3%), LDL-cholesterol
      (E/D: -4.5%; CEE/MPA: -11.3%), HDL-cholesterol (E/D: +15.3%; CEE/MPA: +7.5%),
      triglycerides (E/D: +9.8%; CEE/MPA: +16.6%), VLDL-triglycerides (E/D: -3.3%;
      CEE/MPA: +10.0%), lipoprotein(a) (E/D: 0.0%; CEE/MPA: -25.2%) and for the ratio
      apolipoprotein B/LDL-cholesterol (E/D: +0.9%; CEE/MPA +5.9%). CONCLUSIONS: E/D
      and CEE/MPA differ in their anti-atherogenic effects on lipids and lipoproteins.
      This however can not easily be translated to differences in clinical
      cardiovascular outcomes.

PMID- 15488355
TI  - Methods, locations, and ease of cigarette access for American youth, 1997-2002.
AB  - BACKGROUND: The purpose of this paper is to examine trends in middle and high
      school students' perceived ease, methods, and locations of access to cigarettes,
      and to assess differences related to their sociodemographic characteristics and
      smoking status. METHODS: Annual data from nationally representative samples of
      8th-, 10th-, and 12th-grade students were analyzed for the 1997-2002 period.
      Analyses were conducted in 2003. RESULTS: Perceived ease of access decreased
      significantly among never and past smokers. Decreased individual purchasing in
      retail outlets, as well as decreased purchasing from vending machines, were
      reported by 8th- and 10th-grade students. All grades reported decreased
      purchasing from self-service placements of cigarettes. Decreases in access were
      not reported across all retailer types, and no significant increases were seen in
      the percent of underage purchasers who reported being asked to show
      identification. Both gender and ethnicity were significantly related to where and
      how underage youth reported obtaining cigarettes. CONCLUSIONS: Cigarette access
      for minors has been declining, but remains high. Findings show that (1) perceived
      access to cigarettes clearly increases with level of smoking, and (2) policies to
      reduce such access may be having an impact as evidenced by decreased retail and
      vending machine purchases and self-service purchases. However, states should
      continue to strengthen efforts to reduce youth cigarette access, especially in
      the areas of confirming buyer age via identification checks, and should make
      efforts to decrease access across all retailer types. Federal regulations like
      those previously implemented by the Food and Drug Administration might strongly
      assist in reducing youth access to cigarettes.

PMID- 15488356
TI  - Longitudinal physical activity and sedentary behavior trends: adolescence to
      adulthood.
AB  - BACKGROUND: There is little national research on longitudinal patterns of
      physical activity and sedentary behavior in ethnically diverse teens as they
      transition to adulthood. METHODS: Longitudinal questionnaire data from U.S.
      adolescents enrolled in Wave I (1994-1995) and Wave III (2001) of the National
      Longitudinal Study of Adolescent Health (n =13,030) were analyzed in January
      2004. Incidence, reversal, and maintenance of achieving five or more weekly bouts
      of moderate to vigorous physical activity (MVPA) and < or =14 hours of weekly TV
      and video viewing, computer/video game use (screen time) were assessed.
      Multinomial logistic regression models examined the likelihood of achieving five
      or more weekly sessions of MVPA week and < or =14 hours screen time per week as
      an adolescent and/or young adult, controlling for household income, parental
      education, age of adolescent, and seasonality. RESULTS: Of those achieving five
      or more weekly sessions of MVPA and < or =14 hours of weekly screen time as
      adolescents, few continued to achieve these favorable amounts of activity (4.4%)
      and screen time (37.0%) as adults. More failed to maintain these favorable
      amounts of activity (31.1%) and screen time (17.3%) into adulthood. Black versus
      white females were more likely to maintain less [corrected] favorable amounts of
      activity from adolescence to adulthood (odds ratio [OR]=3.09; 95% confidence
      interval [CI]=1.49-6.42), while black males (OR=1.50; CI=1.05-2.14) and females
      (OR=2.00; CI=1.40-2.87) were more likely than whites to maintain less (versus
      more) favorable screen time hours. CONCLUSIONS: The vast majority of adolescents
      do not achieve five or more bouts of moderate physical activity per week, and
      continue to fail to achieve this amount of activity into adulthood.

PMID- 15488357
TI  - Reducing medical service utilization by encouraging vaccines: randomized
      controlled trial.
AB  - BACKGROUND: Vaccination against influenza is associated with reductions in
      hospitalizations for heart disease, cerebrovascular disease, pneumonia, or
      influenza, and the risk of death from all causes during the influenza season.
      DESIGN: Randomized controlled trial. PARTICIPANTS: All members enrolled in the
      Blue Cross Blue Shield Association's Government Wide Service Benefit Program in
      the states of Oklahoma, Rhode Island, Kentucky, California, Arizona, Utah, and
      Colorado in October 2002. The sample size was 339,220 members. INTERVENTION: Two
      identical influenza/pneumonia direct mail marketing pieces that encouraged
      members to receive influenza and pneumococcal vaccinations. The study period was
      October 15, 2002 through March 15, 2003 when most influenza cases occur. Data
      were collected in July 2003 and analyzed during August 2003. MAIN OUTCOME
      MEASURES: Administrative claims based on influenza/pneumonia inpatient admissions
      and emergency department (ED) visits. RESULTS: The intervention group experienced
      a 2.62% (p=0.010) higher rate of influenza vaccinations; 4.61% (p=0.080) higher
      rate of pneumonia vaccinations; 9.67% (p=0.136) lower rate of influenza/pneumonia
      inpatient admissions; and 22.64% (p=0.002) lower rate of influenza/pneumonia ED
      visits compared to the control group. The benefit-cost ratio (return on
      investment) from this intervention was estimated to be US dollar 2.21 per dollar
      spent. CONCLUSIONS: Administrative claims data suggest that members respond to
      health plan mailings with an increase in influenza vaccination rates. Health
      plans can cost-effectively impact medical service utilization and vaccination
      rates by mailing information to their members.

PMID- 15488358
TI  - Promoting and maintaining physical activity in people with type 2 diabetes.
AB  - BACKGROUND: Limited research has investigated how to promote physical activity in
      people with type 2 diabetes. This study evaluated physical activity counseling
      over 12 months in people with type 2 diabetes. DESIGN: Participants were given
      standard exercise information and randomly assigned to receive physical activity
      counseling or not. Data were collected from September 2000 through to September
      2002 and analyzed from October 2002 to February 2003. SETTING/PARTICIPANTS:
      Diabetes outpatient clinic. Seventy inactive people with type 2 diabetes.
      INTERVENTION: Physical activity counseling, based on the transtheoretical model,
      combined motivational theory and cognitive behavioral strategies into an
      individualized intervention to promote physical activity. Consultations were
      delivered at baseline and 6 months, with phone calls at 1 and 3 months post
      consultation. MAIN OUTCOME MEASURES: Changes from baseline at 12 months in
      physical activity (7-day recall and accelerometer), stages and processes of
      exercise behavior change. RESULTS: Between-group differences were recorded in
      physical activity (recall and accelerometer) at 12 months (p <0.01). Experimental
      participants significantly increased total activity (median difference, 115
      minutes; 95% confidence interval [CI]=73-150 minutes). Control participants
      recorded no significant change (median difference, -15 minutes; 95% CI=-53-13
      minutes). The accelerometer experimental participants recorded no significant
      change (mean difference, 416,632 counts; 95% CI=-27,743, 1,051,007 counts/week),
      while control participants recorded a significant decrease (mean difference, 
      669,061 counts; 95% CI=-1,292,285, -45,837 counts/week). At 12 months, more
      experimental participants compared to controls were in active stages of
      behavior(6-month chi(2)=26.4, p <0.01; 12-month chi(2)=19.9, p <0.01,
      respectively). Between-group differences were recorded at 12 months for the
      frequency of using all processes (p <0.01), except dramatic relief and stimulus
      control. CONCLUSIONS: Physical activity counseling was effective for promoting
      physical activity over 12 months in people with type 2 diabetes.

PMID- 15488359
TI  - Physical activity promotion in primary care: bridging the gap between research
      and practice.
AB  - BACKGROUND: While a growing literature supports the effectiveness of physical
      activity interventions delivered in the primary care setting, few studies have
      evaluated efforts to increase physician counseling on physical activity during
      routine practice (i.e., outside the context of controlled research). This paper
      reports the results of a dissemination trial of a primary care-based physical
      activity counseling intervention conducted within the context of a larger, multi
      strategy, Australian community-based, physical activity intervention, the 10,000
      Steps Rockhampton Project. METHODS: All 23 general practices and 66 general
      practitioners (GPs, the Australian equivalent of family physicians) were invited
      to participate. Practice visits were made to consenting practices during which
      instruction in brief physical activity counseling was offered, along with
      physical activity promotion resources (print materials and pedometers). The
      evaluation, guided by the RE-AIM framework, included collection of process data,
      as well as pre- and post-intervention data from a mailed GP survey, and data from
      the larger project's random-digit-dialed, community-based, cross-sectional
      telephone survey that was conducted in Rockhampton and a comparison community.
      RESULTS: Ninety-one percent of practices were visited by 10,000 Steps staff and
      agreed to participate, with 58% of GPs present during the visits. General
      practitioner survey response rates were 67% (n =44/66 at baseline) and 71% (n
      =37/52, at 14-month follow-up). At follow-up, 62% had displayed the poster, 81%
      were using the brochures, and 70% had loaned pedometers to patients, although the
      number loaned was relatively small. No change was seen in GP self-report of the
      percentage of patients counseled on physical activity. However, data from the
      telephone surveys showed a 31% increase in the likelihood of recalling GP advice
      on physical activity in Rockhampton (95% confidence interval [CI]=1.11-1.54)
      compared to a 16% decrease (95% CI=0.68-1.04) in the comparison community.
      CONCLUSIONS: This dissemination study achieved high rates of GP uptake,
      reasonable levels of implementation, and a significant increase in the number of
      community residents counseled on physical activity. These results suggest that
      evidence-based primary care physical activity counseling protocols can be
      translated into routine practice, although the initial and ongoing investment of
      time to develop partnerships with relevant healthcare organizations, and the
      interest generated by the overall 10,000 Steps program should not be
      underestimated.

PMID- 15488360
TI  - Physical inactivity: direct cost to a health plan.
AB  - PURPOSE: The purpose of this study was to estimate the total medical expenditures
      attributable to physical inactivity patterns among members of a large health
      plan, Blue Cross Blue Shield of Minnesota. METHODS: The study used a cost-of
      illness approach to attribute medical and pharmacy costs for specific diseases to
      physical inactivity in 2000. Relative risks come from the scientific literature,
      demonstrating that heart disease, stroke, hypertension, type 2 diabetes, colon
      cancer, breast cancer, osteoporosis, depression, and anxiety are directly related
      to individual physical activity patterns in adults. Data sources were the 2000
      Behavioral Risk Factor Surveillance System and medical claims incurred in 2000
      among 1.5 million health plan members aged > or =18 years. Primary analysis was
      completed in 2002. RESULTS: Nearly 12% of depression and anxiety and 31% of colon
      cancer, heart disease, osteoporosis, and stroke cases were attributable to
      physical inactivity. Heart disease was the most expensive outcome of physical
      inactivity within the health plan population, costing US dollar 35.3 million in
      2000. Total health plan expenditures attributable to physical inactivity were US
      dollar 83.6 million, or US dollar 56 per member. CONCLUSIONS: This study confirms
      the growing body of research quantifying physical inactivity as a serious and
      expensive public health problem. The costs associated with physical inactivity
      are borne by taxpayers, employers, and individuals in the form of higher taxes to
      subsidize public insurance programs and increased health insurance premiums.

PMID- 15488361
TI  - Involvement in physical activity and risk for nearly lethal suicide attempts.
AB  - BACKGROUND: Although substantial research suggests that involvement in physical
      activity is associated with mental health benefits, relatively little is known
      about the association between physical activity and suicidal behavior. This study
      compared reports of recent physical activity among those surviving a nearly
      lethal suicide attempt to reports from community controls. METHODS: Analyses were
      conducted on data collected between November 1992 and July 1995 for a population
      based, case-control study of nearly lethal suicide attempts among people aged 13
      to 34 years. Logistic regression analyses were used to test the association
      between suicide attempts and physical activity, including the intensity,
      frequency, and duration of activity, while controlling for demographic factors
      and potential explanatory variables, such as depression, alcoholism, and the
      presence of a serious medical condition. RESULTS: Suicide attempters were far
      less likely than controls to report involvement in physical activity in the past
      month (48% vs 85%, respectively). Intensity, frequency, and duration of activity
      did not affect this association. The association persisted after adjusting for
      demographics and potential explanatory variables. CONCLUSIONS: Additional
      research is needed to explain the process through which the association occurs.
      The strong protective association observed is consistent with other research on
      the mental health benefits of physical activity and recommendations of
      involvement in regular physical activity.

PMID- 15488362
TI  - Smoking-related attitudes and clinical practices of medical personnel in
      Minnesota.
AB  - CONTEXT: Effective clinic-based, smoking-cessation activities are not widely
      implemented. OBJECTIVE: To compare and contrast the smoking-cessation attitudes
      and clinical practices of five types of primary healthcare team members. DESIGN
      AND SETTING: From July to October 2002, a cross-sectional survey was mailed to
      randomly selected primary care physicians (MDs), advanced practice nurses
      (APRNs), registered nurses (RNs), licensed practical nurses (LPNs), and medical
      assistants (MAs). MAIN OUTCOME MEASURES: Factors associated with limited smoking
      cessation service delivery. RESULTS: The overall response rate was 68% (n =3021).
      Most respondents reported that patients' smoking status was consistently
      documented at their clinic (79%); other system prompts were less common (30%).
      Many respondents reported documenting smoking status or recommending quitting;
      few reported consistently assessing, assisting, or arranging follow-up. The mean
      rank of smoking cessation as an important preventive service among nine
      preventive services declined from MDs (1.9) to APRNs (2.5), RNs (3.4), LPNs
      (4.2), and MAs (4.6). Smoking prevalence increased from 1% in MDs to 3% APRNs, 9%
      RNs, 17% LPNs, and 22% MAs. Those who reported no consistent smoking-cessation
      service delivery were more likely to be RNs, LPNs, or MAs, currently smoke, and
      work more hours. They were less likely to consider patients receptive to
      cessation messages, to consider themselves qualified to counsel on smoking, or to
      work in clinics that had smoking-cessation guidelines or system prompts such as
      chart reminders. CONCLUSIONS: Smoking-cessation service delivery may be enhanced
      if educational offerings, system changes, and training include all clinical staff
      members.

PMID- 15488363
TI  - The association between length of residence and obesity among Hispanic
      immigrants.
AB  - BACKGROUND: Newly arrived Hispanic immigrants are generally healthier than the
      U.S.-born population, but this distinction tends to diminish over time as
      immigrants adapt to a new and different sociocultural environment. OBJECTIVE:
      This study sought to determine whether length of residence in the United States
      was associated with obesity (body mass index [BMI]>30 kg/m(2)) among Hispanic
      immigrants. METHODS: Data for 2420 foreign-born Hispanic adults aged > or =18
      years were obtained from the 1998 National Health Interview Survey. RESULTS: The
      prevalence of obesity among those with 0 to 4, 5 to 9, 10 to 14, and > or =15
      years of residence in the United States was 9.4%, 14.5%, 21.0%, and 24.2%,
      respectively. A logistic regression model adjusted for smoking, physical
      inactivity, self-assessed health, chronic conditions, functional limitations,
      nonspecific psychological distress, several sociodemographic characteristics, and
      access to health services found that longer-term Hispanic immigrants (> or =15
      years) experienced a nearly four-fold greater risk of obesity than did recent
      immigrants (<5 years). CONCLUSIONS: The higher risk for obesity associated with
      length of residence may be due to acculturation processes such as the adoption of
      the unhealthy dietary practices (i.e., a diet high in fat and low in fruits and
      vegetables) and sedentary lifestyles of the host country. The results of this
      study may facilitate the planning of public health interventions that are
      directed at subgroups of the Hispanic population.

PMID- 15488364
TI  - A structured review of the effect of economic incentives on consumers' preventive
      behavior.
AB  - Improving participation in preventive activities will require finding methods to
      encourage consumers to engage in and remain in such efforts. This review assesses
      the effects of economic incentives on consumers' preventive health behaviors. A
      study was classified as complex preventive health if a sustained behavior change
      was required of the consumer; if it could be accomplished directly (e.g.,
      immunizations), it was considered simple. A systematic literature review
      identified 111 randomized controlled trials of which 47 (published between 1966
      and 2002) met the criteria for review. The economic incentives worked 73% of the
      time (74% for simple, and 72% for complex). Rates varied by the goal of the
      incentive. Incentives that increased ability to purchase the preventive service
      worked better than more diffuse incentives, but the type matters less than the
      nature of the incentive. Economic incentives are effective in the short run for
      simple preventive care, and distinct, well-defined behavioral goals. Small
      incentives can produce finite changes, but it is not clear what size of incentive
      is needed to yield a major sustained effect.

PMID- 15488365
TI  - Memory and attention in Obsessive-Compulsive Disorder: a review.
AB  - The present manuscript reviewed studies investigating biases and deficits in
      memory and attention related to Obsessive-Compulsive Disorder (OCD). Although the
      research has been mixed concerning memory for verbal information, there is more
      consistent evidence suggesting impairment for non-verbal information,
      particularly for complex visual stimuli and the individual's own actions.
      Further, a number of studies indicate that patients with OCD report less
      confidence in their judgments about recognition memory. Finally, OCD appears to
      be associated with an attentional bias favoring threatening information, as well
      as reduced levels of cognitive inhibition. The manuscript concludes with a number
      of recommendations for future research.

PMID- 15488366
TI  - Differentiating hypochondriasis from panic disorder.
AB  - Hypochondriasis and panic disorder are both characterized by prevalent health
      anxieties and illness beliefs. Therefore, the question as to whether they
      represent distinct nosological entities has been raised. This study examines how
      clinical characteristics can be used to differentiate both disorders, taking the
      possibility of mixed symptomatologies (comorbidity) into account. We compared 46
      patients with hypochondriasis, 45 with panic disorder, and 21 with comorbid
      hypochondriasis plus panic disorder. While panic patients had more comorbidity
      with agoraphobia, hypochondriasis was more closely associated with somatization.
      Patients with panic disorder were less pathological than hypochondriacal patients
      on all subscales of the Whiteley Index (WI) and the Illness Attitude Scales (IAS)
      except for illness behavior. These differences were independent of somatization.
      Patients with hypochondriasis plus panic had higher levels of anxiety, more
      somatization, more general psychopathology and a trend towards increased health
      care utilization. Clinicians were able to distinguish between patient groups
      based upon the tendency of hypochondriacal patients to demand unnecessary medical
      treatments. These results confirm that hypochondriasis and panic disorder are
      distinguishable clinical conditions, characterized by generally more
      psychopathology and distress in hypochondriasis.

PMID- 15488367
TI  - Factor structure and construct validity of the Anxiety Sensitivity Index among
      island Puerto Ricans.
AB  - The factor structure and convergent and discriminant validity of the Anxiety
      Sensitivity Index (ASI) were examined among a sample of 275 island Puerto Ricans.
      Results from a confirmatory factor analysis (CFA) comparing our data to factor
      solutions commonly reported as representative of European American and Spanish
      populations indicated a poor fit. A subsequent exploratory factor analysis (EFA)
      indicated that a two-factor solution (Factor 1, Anxiety Sensitivity; Factor 2,
      Emotional Concerns) provided the best fit. Correlations between the ASI and
      anxiety measures were moderately high providing evidence of convergent validity,
      while correlations between the ASI and BDI were significantly lower providing
      evidence of discriminant validity. Scores on all measures were positively
      correlated with acculturation, suggesting that those who ascribe to more
      traditional Hispanic culture report elevated anxiety.

PMID- 15488368
TI  - The effect of the decreased safety behaviors on anxiety and negative thoughts in
      social phobics.
AB  - In order to examine the effect of the decreased safety behaviors on social
      anxiety and negative thoughts and explore the mechanism underlying this effect,
      this study compared three types of exposure namely, exposure with decreased
      safety behaviors under cognitive rationale, exposure with decreased safety
      behaviors under extinction rationale, and exposure with no change in safety
      behavior. Forty-five social phobics were randomly assigned to one of three
      exposure groups. Results showed that exposure with decreased safety behaviors
      under cognitive rationale produced significantly greater reductions in anxiety
      and belief ratings for feared outcomes than exposure with decreased safety
      behaviors under extinction rationale and exposure with no change in safety
      behaviors. These results imply that exposure could be more effective if social
      phobics are encouraged to drop their safety behaviors in the feared social
      situation, and that the cognitive process of disconfirmation of negative thoughts
      is the critical element in determining effectiveness of decreased safety
      behaviors.

PMID- 15488369
TI  - A prospective evaluation of agoraphobia and depression symptoms following panic
      attacks in a community sample of adolescents.
AB  - In a community sample of high schoolers who experienced their first panic attack,
      we examined the prospective relationships among pre-panic vulnerabilities, panic
      attack severity, and post-panic agoraphobia and depression symptoms. Students
      were evaluated yearly over 4 years to test the following four hypotheses: (1) pre
      panic anxiety sensitivity, negative affect, and childhood behavioral inhibition
      will serve as vulnerabilities that predict agoraphobia and depression symptoms
      following a panic attack; (2) these vulnerabilities will lead to more severe
      panic attacks; (3) severe and spontaneous panic attacks will predict subsequent
      agoraphobia and depressive symptoms; and (4) the interaction between panic
      severity and vulnerabilities will be associated with worse outcomes following a
      panic attack. Results supported the first three hypotheses, but no evidence
      emerged for an interactive effect. Findings are discussed in light of recent
      modernized classical conditioning models that address factors contributing to
      development of more severe panic related psychopathology after panic attacks.

PMID- 15488370
TI  - Hypervigilance-avoidance pattern in spider phobia.
AB  - Cognitive-motivational theories of phobias propose that patients' behavior is
      characterized by a hypervigilance-avoidance pattern. This implies that phobics
      initially direct their attention towards fear-relevant stimuli, followed by
      avoidance that is thought to prevent objective evaluation and habituation.
      However, previous experiments with highly anxious individuals confirmed initial
      hypervigilance and yet failed to show subsequent avoidance. In the present study,
      we administered a visual task in spider phobics and controls, requiring
      participants to search for spiders. Analyzing eye movements during visual
      exploration allowed the examination of spatial as well as temporal aspects of
      phobic behavior. Confirming the hypervigilance-avoidance hypothesis as a whole,
      our results showed that, relative to controls, phobics detected spiders faster,
      fixated closer to spiders during the initial search phase and fixated further
      from spiders subsequently.

PMID- 15488371
TI  - Inhibition of return in patients with obsessive-compulsive disorder.
AB  - The present study is aimed at replicating and extending previous results by
      Nelson et al. [Psychiatry Res. 49 (1993) 183], who found decreased inhibition of
      return (IOR) in patients with obsessive-compulsive disorder (OCD). Thirty OCD
      patients, 14 psychiatric, and 14 healthy controls participated in a visual cueing
      experiment. The task required detection of a target stimulus at one of two
      possible locations. Prior to the target, an uninformative cue appeared at one of
      these two locations. The Stimulus Onset Asynchrony (SOA) between the cue and the
      target was systematically varied. We were especially interested in whether
      severity of OCD symptoms would be negatively correlated with inhibition for
      previously occupied locations. In accordance with prior research on healthy
      participants all groups displayed a comparable response pattern: facilitation at
      the short SOA condition and increasing IOR for the longer SOA conditions.
      Medication, comorbid depression, and OCD severity did not consistently moderate
      these effects.

PMID- 15488372
TI  - The relationship between obsessive-compulsive and posttraumatic stress symptoms
      in clinical and non-clinical samples.
AB  - Although case reports suggest the existence of a unique relationship between
      obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD),
      results from large-scale epidemiological and clinical studies have been more
      equivocal. Furthermore, symptom overlap may artificially inflate the significance
      of the relationship between OCD and PTSD. Utilizing the Obsessive-Compulsive
      Inventory [OCI; Psychol. Assess. 10 (1998) 206] and the Posttraumatic Diagnostic
      Scale [PDS; Psychol. Assess. 9 (1997) 445], this study examined the relationship
      between OCD and PTSD symptoms in 128 patients diagnosed with OCD, 109 patients
      diagnosed with PTSD, 63 patients diagnosed with another anxiety disorder, and 40
      college students. Experts in OCD and PTSD independently rated items on the OCI
      and PDS for the degree of overlap across the disorders. On the basis of these
      ratings, we created a scale from each measure that included only non-overlapping
      items. Results revealed that overall symptoms of OCD and PTSD were related in all
      samples. However, after controlling for depression and overlapping symptoms
      simultaneously, this relationship was no longer significant in the OCD and PTSD
      samples, although it remained significant in the anxious and college student
      comparison groups. These results support the presence of a relationship between
      symptoms of OCD and PTSD that may be largely accounted for by a combination of
      symptom overlap and depression.

PMID- 15488373
TI  - Generalized anxiety following unintended pregnancies resolved through childbirth
      and abortion: a cohort study of the 1995 National Survey of Family Growth.
AB  - The psychological consequences of induced abortion are complex and subject to
      both considerable controversy and methodological criticisms. While many women
      report feelings of relief immediately after the procedure, others report feelings
      of anxiety, which they attribute to their abortions. The purpose of the present
      study was to examine risk of generalized anxiety following unintended pregnancies
      ending in abortion or childbirth using a large representative sample of American
      women. Among all women, those who aborted were found to have significantly higher
      rates of subsequent generalized anxiety when controlling for race and age at
      interview. Implications of the findings are discussed. In particular, findings
      highlight the clinical relevance of exploring reproductive history in therapeutic
      efforts to assist women seeking relief from anxiety.

PMID- 15488375
TI  - Selection for 3' end triplets for polymerase chain reaction primers.
AB  - The 3' end of a primer is a key component of PCR primer design. Many
      recommendations for the composition and sequence of the 3' end have been
      suggested based on theoretical considerations, but have not been verified
      experimentally. We analyzed 3' end triplets of PCR primer sequences obtained from
      refereed journal articles, to test those recommendations and to make empirical
      recommendations for primer design. The frequencies of the 64 possible 3'end
      triplets among 2137 PCR primers from the VirOligo database were not uniformly
      distributed. From the analysis, we found that unfavored and preferred 3' end
      triplets existed, and that the apparent preferences were not due to base
      compositions in viral genome sequences. Comparison of the sequences preferred by
      practitioners to those recommended, suggested that no single recommendation is
      entirely satisfactory. We suggest that recommendations be replaced with a scoring
      system incorporating empirical frequencies such as those reported here.

PMID- 15488374
TI  - Genotyping of Clostridium perfringens toxins using multiple oligonucleotide
      microarray hybridization.
AB  - A microarray-based method for characterization of six Clostridium perfringens
      toxin genes: iA (iota toxin), cpa (alpha toxin), cpe (enterotoxin E), etxD
      (epsilon toxin), cpb1 (beta toxin 1),and cpb2 (beta toxin 2) was developed and
      evaluated using 17 C. perfringens isolates. Three individual oligonucleotide
      probes (oligoprobes), complementary to the unique sequences of each toxin gene,
      were designed and immobilized on a surface of aldehyde-coated glass slides.
      Multiplex PCR was used to simultaneously amplify DNA target regions of all six
      genes. Single-stranded DNA (ssDNA) samples for microarray analysis were prepared
      by following a primer extension of amplicons in the presence of one primer.
      Fluorescent moieties (Cy3) were incorporated into the ssDNA by chemical
      modification of guanine bases. The presence of toxin genes in C. perfringens was
      established by hybridization of the fluorescently labeled ssDNA representing
      different samples to the microarray gene-specific oligoprobes. Results of the
      study showed sensitivity and specificity of genotyping C. perfringens using
      multiple microarray-based assays.

PMID- 15488376
TI  - Detection of Staphylococcus aureus enterotoxin A and B genes with PCR-EIA and a
      hand-held electrochemical sensor.
AB  - Two electrochemical assays for detecting Staphylococcus aureus enterotoxin A and
      B genes were developed. The assays are based on PCR amplification with
      biotinylated primers, hybridization to a fluorescein-labeled probe, and detection
      with horseradish peroxidase-conjugated anti-fluorescein antibody using a hand
      held electrochemical detector. The limit of detection (LOD) for both assays was
      approximately 16 copies of the sea and seb genes. The assays were evaluated in
      blinded studies, each with 81 samples that included genomic and cloned S. aureus
      DNA, and genomic DNA from Alcaligens, Bacillus, Bacteroides, Bordetella,
      Borkholderia, Clostridium, Comanonas, Enterobacter, Enterococcus, Escherichia,
      Francisella, Haemophilus, Klebsiella, Listeria, Moraxella, Neisseria, Proteus,
      Pseudomonas, Salmonella, Serratia, Shigella, Streptococcus, Vibrio and Yersinia
      species. Both assays showed 100% sensitivity. The specificity was 96% for the SEA
      assay and 98% for the SEB assay. These results demonstrate the feasibility of
      performing probe-based detection of PCR products with a low-cost, hand-held,
      electrochemical detection device as a viable alternative to colorimetric enzyme
      linked assays of PCR products.

PMID- 15488377
TI  - A rapid and sensitive magnetic bead-based immunoassay for the detection of
      staphylococcal enterotoxin B for high-through put screening.
AB  - Staphylococcal enterotoxin B (SEB) is one of many toxins produced by the Gram
      positive bacterium Staphylococcal aureus. While SEB is known as the causative
      agent of certain food poisonings it is also considered a biological Select Agent.
      Thus, rapid and accurate identification of SEB during either surveillance or in
      response to a biothreat is critical to the mitigation of the suspect agent. This
      report presents an improved method for the detection of SEB based on a SEB
      specific, two-antibody system where one antibody was bound to a magnetic bead
      particle while the other was labeled with Alexa fluor 647. The assay consisted of
      one incubation period for 30 minutes where all reagents necessary to detect SEB
      were included. Using this assay 100 pg of recombinant purified SEB, as well as
      SEB from the culture supernatant of several strains of methicillin-resistant S.
      aureus were detected with fidelity. This assay presents improvements over current
      assays in terms of a combination of the reduction in assay time length, assay
      sensitivity, ease of use, and application to automated high-throughput analysis.
      Additionally, this assay can be easily modified to detect a wide range of
      proteins and whole organisms.

PMID- 15488378
TI  - An isothermal amplification system based on the tandem-repeated DNA probe.
AB  - The hybridization methods and polymerase-based amplification methods are usually
      employed to detect pathogens and gene expressions quantitatively in clinical
      practices nowadays. However, the sensitiveness of the former and the specificity
      of the latter are not yet satisfied. To solve this problem, some promising
      comprehensive methods have been developed recently. Here we reported a new
      comprehensive method, a tandem repeated DNA probe-based amplification (TRPBA)
      system. To establish the TRPBA, TR48, an artificial tandem repeated DNA probe
      with 48 repeats of a 50 base pair unit was constructed. It could be efficiently
      amplified by Bst DNA polymerase at 61 degrees C for only 1 h. The products were
      analyzed either by direct gel electrophoresis or by gel electrophoresis after the
      digestion with restriction endonuclease HincII. The sensitiveness was as few as
      100 copies per test, which was comparable with PCR-based techniques. The TR48
      splicing with the DNA fragment of hepatitis B virus used as probe could
      successfully develop TRPBA to detect hepatitis B virus DNA. The TRPBA can be used
      in the future to detect many other genes or microorganisms simply by splicing
      TR48 with their DNA fragments. Thus, TRPBA might be useful because of its
      sensitiveness and simpleness.

PMID- 15488379
TI  - Molecular identification of enteroviruses responsible for an outbreak of aseptic
      meningitis; implications in clinical practice and epidemiology.
AB  - An outbreak of aseptic meningitis was recorded in Greece during the year 2001.
      Detection of the clinical strains was achieved by performing reverse
      transcription-polymerase chain reaction (RT-PCR) on RNA isolated from cell
      cultures inoculated with treated faecal material from the patients. Serotypic
      identification of the isolates with mixed equine antisera pools followed and the
      RT-PCR amplicons were further studied by restriction fragment length polymorphism
      analysis and sequencing. Fifty-three clinical enterovirus strains were isolated
      from respective cases of suspected enterovirus infection, most of which showed
      the clinical symptoms of aseptic meningitis. Echovirus (ECV) 6 was the most
      frequently isolated serotype, followed by coxsackie B viruses, ECV13, poliovirus
      type 1 (PV1) vaccine strain and ECV30. Nucleotide sequence analysis showed the
      existence of different genetic groups on the basis of the 5'-untranslated region
      (5'-UTR) of the genome, which circulated in the population during the same time
      period. Different serotypes belonged to the same genetic group and vice versa.
      The 5'-UTR seems to be appropriate for the investigation of enterovirus evolution
      and epidemiology.

PMID- 15488380
TI  - Taxonomic and phylogenetic status of non-tuberculous mycobacteria in a Caribbean
      setting.
AB  - This report describes detailed taxonomic and phylogenetic analysis of 15 non
      tuberculous mycobacteria (NTMs) isolated from human pathological specimens in a
      Caribbean setting (12 slow-growers and three rapid-growers) that were not
      identified by cultural and biochemical tests and drug-susceptibility results.
      These isolates were further studied using PCR restriction fragment length
      polymorphism analysis (PRA) of a 441bp hsp65 fragment, as well as the sequencing
      of 16S rDNA and hsp65 DNA, and HPLC of the mycolic acids. Our results showed that
      taxonomic position of well-defined NTMs was resolved by PRA and sequencing of
      hsp65, nonetheless, it was not suitable to investigate rarely observed or new
      strains that required 16S rDNA sequencing and HPLC for a definite response.
      Unrooted neighbor-joining phylogenetic trees were drawn based upon the 16S rDNA
      and hsp65 sequences of the 15 NTMs compared with those from described species (73
      for 16S rDNA and 45 for hsp65). For most of the NTMs not showing an exactly
      matching sequence with either hsp65 or 16S rDNA in the GenBank, the phylogenetic
      tree was able to provide with useful indications about their relatedness to known
      species. In such a case, a concording HPLC pattern with the sequence data and the
      place of the strain within the tree could lead to a potential identification. We
      also identified three identical isolates that define a new mycobacterial species
      within the group of M. simiae-related mycobacteria. The isolation and
      characterization of mycobacteria from new settings may lead to identify potential
      pathogens that may propogate in future because of increased human migration,
      travels, and climatic and ecological changes of the modern world.

PMID- 15488381
TI  - Comparison of PCR-ELISA and LightCycler real-time PCR assays for detecting
      Salmonella spp. in milk and meat samples.
AB  - In a previous study, we reported the performance of a PCR assay amplifying 285-bp
      of the invA gene of Salmonella spp. through an international ring-trial involving
      four participating laboratories [Int. J. Food Microbiol. 89 (2003) 241]. Based on
      the validated set of primers and recent advancements in PCR technology, we have
      designed two specific PCR assays for detecting Salmonella spp. We have compared
      PCR-enzyme-linked immunosorbent assay (PCR-ELISA) and LightCycler real-time PCR
      assay (LC-PCR) with the standard ISO 6579 bacteriological reference method. The
      two PCR tests incorporated an internal amplification control (IAC) co-amplified
      with the invA gene of Salmonella to monitor potential PCR inhibitors and ensure
      successful amplification. The selectivity study involved 84 Salmonella and 44 non
      Salmonella strains and the samples tested were represented by 60 artificially
      contaminated samples of fish, minced beef and raw milk, and 92 naturally
      contaminated milk and meat samples. When using either PCR-ELISA or LC-PCR assays,
      only Salmonella strains were detected. PCR-ELISA and LC-PCR assays gave with pure
      Salmonella cultures the same detection limit level of 10(3)CFU/ml, which
      corresponds respectively to 50 and 10 cells per PCR tube. Data on artificially
      contaminated samples indicated that both PCR methods were able to detect after
      enrichment less than five Salmonella cells in 25 g of food, giving 100%
      concordance with the ISO 6579 reference method. The results on naturally
      contaminated samples demonstrated that despite certain inhibition problems, LC
      PCR and PCR-ELISA assays were highly specific and sensitive, and provide a
      powerful tool for detection of Salmonella in food samples.

PMID- 15488382
TI  - Identification of Flavobacterium columnare by a species-specific polymerase chain
      reaction and renaming of ATCC43622 strain to Flavobacterium johnsoniae.
AB  - Species-specific polymerase chain reaction (PCR) primers have been designed to
      identify the causative agent of columnaris disease, Flavobacterium columnare. The
      16S rRNA gene sequences of F. columnare (eight sequences representing the
      different genotypes of the species) and related species (18 sequences) were
      aligned and compared to choose specific regions that are unique to F. columnare
      and do not have significant intraspecies variability. The species-specific
      regions in the 16S rRNA gene were used to design a pair of species-specific PCR
      primers, ColF and ColR. The PCR technique produced a specific amplicon of about
      675 base pairs (bp) in 27 isolates of F. columnare and there was no amplification
      in the closely related species. The specificity of the amplified product was
      confirmed by digesting with HhaI. The PCR primers did not produce a 675 bp
      product with F. columnare ATCC43622 strain. This ATCC43622 strain was
      characterized by biochemical and ribotyping methods and renamed Flavobacterium
      johnsoniae. The American Type Culture Collection has confirmed these findings and
      made the change.

PMID- 15488383
TI  - Differential detection of B. pertussis from B. parapertussis using a polymerase
      chain reaction (PCR) in presence of SYBR green1 and amplicon melting analysis.
AB  - Nucleic acid (DNA) from control stock strains of B. pertussis and B.
      parapertussis (B. pertussis strain # 9797 and B. parapertussis strain # 15234
      from ATCC) was amplified by polymerase chain reaction (PCR) targeting pertussis
      toxin (PT) promotor region, in presence of SYBR green1 a dye that fluoresces on
      binding specifically to double stranded DNA; and fluorescent melting profile of
      amplicon (amplified DNA) was studied. Amplicon of B. pertussis and B.
      parapertussis generated distinctly different melting bands with melting
      temperature (Tm) at 89.8 and 91.7 degrees C, respectively. Melting profile and Tm
      of each randomly selected isolates of B. pertussis and B. parapertussis was
      identical to that of respective control strains. Distinct difference in Tm
      between B. pertussis and B. parapertussis specific amplicons allowed differential
      detection of the two Bordetella species based on a single PCR product. The
      amplified product of serial diluted control stock of bacteria was analyzed by
      both agarose gel electrophoresis and melting profile analysis. The analytical
      sensitivity of detection (1-10 CFU equivalent in the tested volume) by melting
      profile and Tm analysis was in agreement with that obtained by agarose gel
      analysis.

PMID- 15488385
TI  - Bacterial gene regulation: from transcription attenuation to riboswitches and
      ribozymes.
AB  - Since the discovery of transcription attenuation as a mechanism of bacterial gene
      regulation, a broad variety of attenuation mechanisms have been unveiled and
      analysed. In 2002, the first convincing experimental evidence for metabolite
      mediated attenuation, termed riboswitch, was published. Subsequently,
      riboswitches have been found to be widespread among bacteria and are also used in
      some eukaryotes. A surprising new finding has been a riboswitch acting as a
      metabolite-responsive ribozyme - the first new naturally occurring ribozyme
      discovered since 1990.

PMID- 15488384
TI  - Overcoming bacterial DNA contamination in real-time PCR and RT-PCR reactions for
      LacZ detection in cell therapy monitoring.
AB  - Since the introduction of the polymerase chain reaction the presence of
      contaminating bacterial DNA in the Taq polymerase preparations has hampered the
      use of this technique in microbiology. Lately, this inconvenience has equally
      impeded gene quantification in the field of cell or gene therapy, where bacterial
      genes such as LacZ are often used as tags to detect vectors or cells after their
      injection in the recipient organism. Several means to overcome the DNA
      contamination of Taq Polymerase have been reported with variable degrees of
      decontamination efficiency and alteration of the PCR reaction. Here we propose
      two protocols to efficiently quantify DNA or RNA from the LacZ gene by real-time
      PCR using either decontamination by low concentrations of DNAse I prior to PCR
      amplification or a highly purified Taq Polymerase which is devoid of detectable
      contamination.

PMID- 15488386
TI  - An analysis of type-III secretion gene clusters in Chromobacterium violaceum.
AB  - Chromobacterium violaceum is an environmental Gram-negative bacterium that is
      common in soil and water in tropical and sub-tropical regions. It is also a model
      organism for studying quorum-sensing and is a rare but deadly human pathogen.
      Recent completion of the genome sequence of C. violaceum strain ATCC 12472
      revealed the presence of genes associated with type-III secretion systems
      (TTSSs). One of these systems resembles the Spi-1 system found in Salmonella
      enterica, whereas another is similar to the Spi-2 system from the same organism.
      Here, we present a detailed analysis and a fresh annotation of the two gene
      clusters. Moreover, we highlight the presence of several genes encoding putative
      type-III effector proteins that lead us to predict that this organism can
      manipulate vesicular trafficking, the actin cytoskeleton and apoptotic pathways
      within mammalian cells to its own advantage.

PMID- 15488387
TI  - Insights into the evolution of phytopathogens.

PMID- 15488388
TI  - Toll-like receptors as an escape mechanism from the host defense.
AB  - Toll-like receptors (TLRs) are probably the most important class of pattern
      recognition receptors. Recognition of pathogen-associated molecular patterns
      (PAMPs) by TLRs, either alone or in heterodimerization with other TLR or non-TLR
      receptors, induces the production of signals that are responsible for the
      activation of genes important for an effective host defense, especially those of
      proinflammatory cytokines. Recent studies also suggest that pathogenic
      microorganisms can modulate or interfere with TLR-mediated pattern recognition
      and can use TLRs as an escape mechanism from the host defense. Three major TLR
      mediated escape mechanisms have been identified: TLR2-induced immunosuppression,
      especially through induction of interleukin (IL)-10 release; blockade of TLR
      recognition; and TLR-mediated induction of viral replication. Thus, TLR signals
      are not only beneficial to the host, but in certain situations the activation of
      particular TLR responses by microorganisms might serve as an escape mechanism
      from the host defense.

PMID- 15488389
TI  - NikR-mediated regulation of Helicobacter pylori acid adaptation.
AB  - Nickel is the cofactor of the Helicobacter pylori urease enzyme, a factor
      essential for the chronic colonization of the acidic hostile environment in the
      human stomach. The NikR regulatory protein directly controls urease expression
      and regulates the uptake of nickel, and is also able to regulate the expression
      of other regulatory proteins including the iron-responsive regulator Fur. Through
      regulatory crosstalk and overlapping regulons, the NikR protein controls the
      expression of many systems important for colonization and acid adaptation.
      Despite the paucity of regulatory proteins, this enables H. pylori to optimally
      adapt to conditions in the stomach, making it one of the most successful human
      pathogens.

PMID- 15488390
TI  - The LCR of EBV makes Burkitt's lymphoma endemic.
AB  - The spectacular ability of Epstein-Barr virus (EBV) to immortalize and
      morphologically transform human B cells in vitro to lymphoblastoid cell lines
      (LCLs) is central to most molecular models of viral oncogenesis. However, binding
      of transcription factor and oncoprotein c-Myc to the major locus control region
      (LCR) of the viral genome directs us to an alternative model for the origin of
      Burkitt's lymphoma (BL). In this model, improved nuclear maintenance of the viral
      genome and the continuous expression of anti-apoptotic functions in B cells
      exhibiting class I EBV latency contribute to the generation of BL, without any
      detour through EBV nuclear antigen (EBNA) 2-driven B-cell immortalization (also
      called class III latency).

PMID- 15488392
TI  - Bacterial flagellins: mediators of pathogenicity and host immune responses in
      mucosa.
AB  - Flagella contribute to the virulence of pathogenic bacteria through chemotaxis,
      adhesion to and invasion of host surfaces. Flagellin is the structural protein
      that forms the major portion of flagellar filaments. Thus, flagellin consists of
      a conserved domain that is widespread in bacterial species and is dedicated to
      filament polymerization. Conversely, mammalian hosts detect the conserved domain
      on flagellin monomers through Toll-like receptor (TLR) 5, which triggers
      proinflammatory and adaptive immune responses. This review describes the
      relationships among flagellin molecular structure, bacterial virulence and host
      defenses, with special emphasis on mucosal tissues.

PMID- 15488391
TI  - ESAT-6 proteins: protective antigens and virulence factors?
AB  - The 6kDa early secreted antigenic target from Mycobacterium tuberculosis, ESAT-6,
      is the prototype of a novel family of small proteins of unknown function produced
      by Actinobacteria. Export of ESAT-6, a potent T-cell antigen, and related
      proteins requires a dedicated secretory apparatus that is encoded by a cluster of
      genes, several of which also code for proteins that are recognized strongly by T
      cells. ESAT-6 systems can thus be considered as immunogenicity islands and there
      is growing evidence that the corresponding genes are subject to selective
      pressure imposed by the immune system of the host. Recently, there has been major
      progress in understanding the biogenesis, secretion and antigenicity of ESAT-6
      proteins and, at least in the case of ESAT-6 system 1, in unravelling their role
      in pathogenicity. Here, we discuss these findings and their implications for the
      development of new therapeutic and prophylactic interventions against
      tuberculosis.

PMID- 15488393
TI  - Recent advances on the development of bacterial poles.
AB  - In rod-shaped bacteria, a surprisingly large number of proteins are localized to
      the cell poles. Polar positioning of proteins is crucial to many fundamental
      cellular processes. Formation of the pole occurs at the time of a prior cell
      division event and involves coordination of the cell division machinery with
      septal placement of newly-synthesized peptidoglycan. Development of polar
      peptidoglycan and outer membrane depends on the formation of the cytokinetic FtsZ
      ring at midcell. By contrast, positioning of at least two polar proteins depends
      on signals independent of both the assembly of the FtsZ ring and the synthesis of
      septal and polar peptidoglycan. We propose a model for distinct but interrelated
      developmental pathways for polar cell envelope synthesis and positional
      information recognized by polar proteins.

PMID- 15488394
TI  - A solution to the dynamical inverse problem of EEG generation using
      spatiotemporal Kalman filtering.
AB  - We present a new approach for estimating solutions of the dynamical inverse
      problem of EEG generation. In contrast to previous approaches, we reinterpret
      this problem as a filtering problem in a state space framework; for the purpose
      of its solution, we propose a new extension of Kalman filtering to the case of
      spatiotemporal dynamics. The temporal evolution of the distributed generators of
      the EEG can be reconstructed at each voxel of a discretisation of the gray matter
      of brain. By fitting linear autoregressive models with neighbourhood interactions
      to EEG time series, new classes of inverse solutions with improved resolution and
      localisation ability can be explored. For the purposes of model comparison and
      parameter estimation from given data, we employ a likelihood maximisation
      approach. Both for instantaneous and dynamical inverse solutions, we derive
      estimators of the time-dependent estimation error at each voxel. The performance
      of the algorithm is demonstrated by application to simulated and clinical EEG
      recordings. It is shown that by choosing appropriate dynamical models, it becomes
      possible to obtain inverse solutions of considerably improved quality, as
      compared to the usual instantaneous inverse solutions.

PMID- 15488396
TI  - Distributed digit somatotopy in primary somatosensory cortex.
AB  - We obtained high-resolution somatotopic maps of the human digits using 4.0 T
      functional magnetic resonance imaging (fMRI). In separate experiments, the volar
      surface of either the right thumb, index, or ring finger was stimulated in a
      sliding-window fashion in both distal-to-proximal and proximal-to-distal
      directions using a custom-built pneumatic apparatus. Analysis of the functional
      images was restricted to Brodmann's areas 3b and 1 and control areas 4 and 3a, as
      well as a randomized simulation of the functional data in each of these areas.
      Using in-house algorithms, we detected discrete regions of cortical activation
      showing phase reversal coinciding with alternation in stimulation direction. Most
      stimulation-related phase maps of the digits were obtained in areas 3b and 1,
      rather than areas 3a or 4, despite the somatic input to the latter two areas. The
      area 3b and 1 representations thus appear to be relatively discrete and
      somatotopic compared to other somatic processing regions. Our results within
      areas 3b and 1 confirm the nonlinear mapping of the body surface suggested by
      recordings in nonhuman primates in terms of phase band topography, scaling, and
      frequency relative to the actual digit surfaces. The scaling and frequency
      nonlinearities were more evident within area 3b than area 1, suggesting a
      functional differentiation of these regions as has previously been observed only
      in more invasive recordings. Specifically, the area 1 representations were larger
      overall than those observed in area 3b, and the frequencies of area 3b phase
      bands and voxels were related disproportionately to thumb and index finger
      stimulation and to particular areas on the digit surface, suggesting a weighting
      based in part on receptor distribution.

PMID- 15488395
TI  - Improved delineation of brain tumors: an automated method for segmentation based
      on pathologic changes of 1H-MRSI metabolites in gliomas.
AB  - In this study, we developed a method to improve the delineation of intrinsic
      brain tumors based on the changes in metabolism due to tumor infiltration. Proton
      magnetic resonance spectroscopic imaging ((1)H-MRSI) with a nominal voxel size of
      0.45 cm(3) was used to investigate the spatial distribution of choline-containing
      compounds (Cho), creatine (Cr) and N-acetyl-aspartate (NAA) in brain tumors and
      normal brain. Ten patients with untreated gliomas were examined on a 1.5 T
      clinical scanner using a MRSI sequence with PRESS volume preselection. Metabolic
      maps of Cho, Cr, NAA and Cho/NAA ratios were calculated. Tumors were
      automatically segmented in the Cho/NAA images based on the assumption of Gaussian
      distribution of Cho/NAA values in normal brain using a limit for normal brain
      tissue of the mean + three times the standard deviation. Based on this threshold,
      an area was calculated which was delineated as pathologic tissue. This area was
      then compared to areas of hyperintense signal caused by the tumor in T2-weighted
      MRI, which were determined by a region growing algorithm in combination with
      visual inspection by two experienced clinicians. The area that was abnormal on
      (1)H-MRSI exceeded the area delineated via T2 signal changes in the tumor (mean
      difference 24%) in all cases. For verification of higher sensitivity of our
      spectroscopic imaging strategy we developed a method for coregistration of MRI
      and MRSI data sets. Integration of the biochemical information into a frameless
      stereotactic system allowed biopsy sampling from the brain areas that showed
      normal T2-weighted signal but abnormal (1)H-MRSI changes. The histological
      findings showed tumor infiltration ranging from about 4-17% in areas
      differentiated from normal tissue by (1)H-MRSI only. We conclude that high
      spatial resolution (1)H-MRSI (nominal voxel size = 0.45 cm(3)) in combination
      with our segmentation algorithm can improve delineation of tumor borders compared
      to routine MRI tumor diagnosis.

PMID- 15488397
TI  - Real-time neural activity and connectivity in healthy individuals and
      schizophrenia patients.
AB  - Processing of facial information is distributed across several brain regions, as
      has been shown recently in many neuroimaging studies. Disturbances in accurate
      face processing have been repeatedly demonstrated in different stages of
      schizophrenia. Recently, electroencephalography (EEG) and tomographic analysis of
      average magnetoencephalographic (MEG) data were used to define the latencies of
      significant regional brain activations in healthy and schizophrenic subjects
      elicited during the recognition of facial expression of emotions. The current
      study re-examines these results using tomographic analysis of single trial MEG
      data. In addition to the areas identified by the analysis of the average MEG
      data, statistically significant activity is identified in several other areas,
      including a sustained increase in the right amygdala activity in response to
      emotional faces in schizophrenic subjects. The single trial analysis demonstrated
      that the reduced activations identified from the average MEG signal of
      schizophrenic subjects is due to high variability across single trials rather
      than reduced activity in each single trial. In control subjects, direct measures
      of linkage demonstrate distinct stages of processing of emotional faces within
      well-defined network of brain regions. Activity in each node of the network,
      confined to 30 to 40 ms latency windows, is linked to earlier and later
      activations of the other nodes of the network. In schizophrenic subjects, no such
      well-defined stages of processing were observed. Instead, the activations,
      although strong were poorly linked to each other, managing only isolated links
      between pairs of areas.

PMID- 15488398
TI  - For better or for worse: neural systems supporting the cognitive down- and up
      regulation of negative emotion.
AB  - Functional neuroimaging studies examining the neural bases of the cognitive
      control of emotion have found increased prefrontal and decreased amygdala
      activation for the reduction or down-regulation of negative emotion. It is
      unknown, however, (1) whether the same neural systems underlie the enhancement or
      up-regulation of emotion, and (2) whether altering the nature of the regulatory
      strategy alters the neural systems mediating the regulation. To address these
      questions using functional magnetic resonance imaging (fMRI), participants up-
      and down-regulated negative emotion either by focusing internally on the self
      relevance of aversive scenes or by focusing externally on alternative meanings
      for pictured actions and their situational contexts. Results indicated (1a) that
      both up- and down-regulating negative emotion recruited prefrontal and anterior
      cingulate regions implicated in cognitive control, (1b) that amygdala activation
      was modulated up or down in accord with the regulatory goal, and (1c) that up
      regulation uniquely recruited regions of left rostromedial PFC implicated in the
      retrieval of emotion knowledge, whereas down-regulation uniquely recruited
      regions of right lateral and orbital PFC implicated in behavioral inhibition.
      Results also indicated that (2) self-focused regulation recruited medial
      prefrontal regions implicated in internally focused processing, whereas situation
      focused regulation recruited lateral prefrontal regions implicated in externally
      focused processing. These data suggest that both common and distinct neural
      systems support various forms of reappraisal and that which particular prefrontal
      systems modulate the amygdala in different ways depends on the regulatory goal
      and strategy employed.

PMID- 15488399
TI  - Spatiotemporal wavelet analysis for functional MRI.
AB  - Characterizing the spatiotemporal behavior of the BOLD signal in functional
      Magnetic Resonance Imaging (fMRI) is a central issue in understanding brain
      function. While the nature of functional activation clusters is fundamentally
      heterogeneous, many current analysis approaches use spatially invariant models
      that can degrade anatomic boundaries and distort the underlying spatiotemporal
      signal. Furthermore, few analysis approaches use true spatiotemporal continuity
      in their statistical formulations. To address these issues, we present a novel
      spatiotemporal wavelet procedure that uses a stimulus-convolved hemodynamic
      signal plus correlated noise model. The wavelet fits, computed by spatially
      constrained maximum-likelihood estimation, provide efficient multiscale
      representations of heterogeneous brain structures and give well-identified,
      parsimonious spatial activation estimates that are modulated by the temporal fMRI
      dynamics. In a study of both simulated data and actual fMRI memory task
      experiments, our new method gave lower mean-squared error and seemed to result in
      more localized fMRI activation maps compared to models using standard wavelet or
      smoothing techniques. Our spatiotemporal wavelet framework suggests a useful tool
      for the analysis of fMRI studies.

PMID- 15488401
TI  - Visual search and memory search engage extensive overlapping cerebral cortices:
      an fMRI study.
AB  - Previous studies have investigated neural correlates of visual search and memory
      search independently, but none of those studies examined whether cortical regions
      involved in these searches are overlapping or segregated by directly comparing
      the two types of search. In this study, we compared the cortical regions involved
      in visual search and memory search in the same functional magnetic resonance
      imaging (fMRI) experiment run on the same subjects, using identical stimuli and
      time courses of stimulus presentation. The right dorsolateral prefrontal cortex
      (DLPFC), the left frontal eye field (FEF), the right precuneus and cuneus, and
      the left cerebellum were activated by both visual search and memory search. We
      suggest that the right DLPFC is associated with the process of monitoring and
      manipulating multiple elements, while the left FEF is involved in cognitive
      planning. We also propose that the right precuneus and cuneus as well as the left
      cerebellum are responsible for both spatial and nonspatial shifts of attention,
      including attentional shifts in long-term memory, although each of these regions
      has a slightly different role.

PMID- 15488400
TI  - More workload on the central executive of working memory, less attention capture
      by novel visual distractors: evidence from an fMRI study.
AB  - The present study examined the interaction of the central executive in working
      memory with visual attention. Native Chinese participants were given two versions
      of a number subtraction task, one of low demand and one of high demand, and were
      asked to ignore a simultaneously presented peripheral distractor. The distractor
      could be Chinese or Korean characters, familiar or novel to participants,
      respectively. Compared with the low-demand subtraction task, brain regions
      commonly associated with central executive functions, including left middle
      prefrontal cortex, anterior cingulate cortex, and precentral gyrus/sulcus, were
      significantly activated in the high-demand task. Critically, there was a
      significant interaction between distractor type and task demand. Novel
      distractors captured attention and elicited automatic visual analysis, shown by
      primary visual cortex activation, only when the subtraction task was of low
      demand but not when it was of high demand. The results provide confirmatory
      evidence that the extent to which higher level cognitive resources, specifically,
      the central executive component of working memory, are absorbed by a cognitive
      task has an impact upon automatic processing that occurs in response to
      distracting items.

PMID- 15488402
TI  - Neural networks underlying endogenous and exogenous visual-spatial orienting.
AB  - The orienting of visual-spatial attention is fundamental to most organisms and is
      controlled through external (exogenous) or internal (endogenous) processes.
      Exogenous orienting is considered to be reflexive and automatic, whereas
      endogenous orienting refers to the purposeful allocation of attentional resources
      to a predetermined location in space. Although behavioral, electrophysiological
      and lesion research in both primates and humans suggests that separate neural
      systems control these different modes of orienting, previous human neuroimaging
      studies have largely reported common neuronal substrates. Therefore, event
      related FMRI (ER-FMRI) was used to independently examine different components of
      the orienting response including endogenous facilitation, exogenous facilitation
      and inhibition of return (IOR). In contrast to previous studies, endogenous
      versus exogenous facilitation resulted in widespread cortical activation
      including bilateral temporoparietal junction, bilateral superior temporal gyrus,
      right middle temporal gyrus, right frontal eye field and left intraparietal
      sulcus. Conversely, IOR compared to endogenous facilitation resulted in only a
      single focus of activation in the left superior temporal gyrus. These findings
      suggest that endogenous orienting activates a large cortical network to achieve
      internally generated shifts of attentional resources versus the automatic
      orienting that occurs with exogenous cues. However, similar networks may mediate
      endogenous orienting and IOR. The activation of the temporoparietal junction
      suggests that it is involved in more effortful processes, such as endogenous
      orienting, as well as in attentional reorienting and locating targets. Current
      results are discussed in terms of the functional development of the visual
      spatial attentional system.

PMID- 15488403
TI  - Brain sensorimotor hand area functionality in acute stroke: insights from
      magnetoencephalography.
AB  - An understanding of the functional readjustments that the brain undergoes during
      the early days after a stroke would give us a major insight into how and how much
      neurons are capable to react to an insult. Thirty-two patients affected by an
      acute monohemispheric ischemic stroke were enrolled in the study.
      Magnetoencephalography was used to record the somatosensory-evoked fields (SEF)
      generated in response to median nerve stimulation. Latency, strength, and
      position of the related early cortical components (M20 and M30) were studied both
      separately within each hemisphere, and in terms of interhemispheric differences.
      Interhemispheric cross-correlations among SEF waveshapes in the two hemispheres
      were also investigated. Overall, except for some source displacement possibly
      induced by the perilesional edema, results did not demonstrate any unusual neural
      recruitment. The severity of the clinical picture was found related to the
      sources' strengths (both as absolute values and as interhemispheric differences),
      to excessive interhemispheric differences in SEF waveshapes and in the M30
      latencies. Signs of an enhanced excitability were present in the affected
      hemisphere (AH) following a cortical lesion, usually in combination with
      preserved hand functionality. An enhanced excitability of the unaffected
      hemisphere (UH) was paired with larger lesions with cortical involvement; signs
      compatible with an abnormal transcallosal transmission and intracortical function
      of inhibitory GABAergic interneurons in the AH were found subtending UH
      enhancement. Spared responsiveness from Brodmann's area (BA) 2 and posterior
      parietal areas despite an altered response from BA 3b was found in six patients,
      combined to high hand functionality. Present results in acute phase increase the
      knowledge of the mechanisms governing brain adaptation/reaction capabilities, for
      future efforts to establish therapeutic and rehabilitative procedures.

PMID- 15488405
TI  - Detection of diffuse abnormal perfusion in SPECT using a normal brain atlas.
AB  - Visual assessment, with significant inter- or intraobserver variability, is still
      the norm for the evaluation of Single Photon Emission Computerized Tomography
      (SPECT) cerebral perfusion studies. We present in this paper an automated method
      for screening SPECT studies to detect diffuse disseminated abnormalities based on
      a computerized atlas of normal regional cerebral blood flow (rCBF). To generate
      the atlas, a set of normal brain SPECT studies are registered together. The atlas
      contains the intensity mean, the nonlinear displacement mean, and the variance of
      the activity pattern. A patient is then evaluated by registering his or her SPECT
      volume to the atlas and computing the nonlinear 3-D displacement of each voxel
      needed for the best shape fit to it. A voxel is counted as "abnormal" if the
      intensity difference between the atlas and the registered patient (or if the 3-D
      motion necessary to move the voxel to its registered position) is superior to 3
      SD of normal mean. The number of abnormal voxels is used to classify studies. We
      validated this approach on 24 SPECT perfusion studies selected visually for
      having clear diffuse anomalies and 21 normal studies. A Markovian segmentation
      algorithm is also used to identify the white and gray matters for regional
      analysis. Based on the number of abnormal voxels, two supervised classifiers were
      tested: (1) minimum distance-to-mean and (2) Bayesian. The analysis of the
      intensity and displacement "abnormal" voxels allow one to achieve an 80% correct
      classification rate for the whole brain and a 93% rate if we consider only voxels
      in the segmented gray matter region.

PMID- 15488404
TI  - Magnetoencephalographic gamma-band responses to illusory triangles in humans.
AB  - Electroencephalography studies have suggested that the perception of illusory
      figures is associated with increases in gamma-band activity putatively reflecting
      the formation of synchronously firing neuronal assemblies. Here we assessed
      magnetoencephalographic gamma-band activity, which has been shown to be
      topographically more focal than in electroencephalogram. In line with functional
      brain imaging findings, we hypothesized gamma-band activity over ventral visual
      stream areas. In addition, we expected that the analysis of oscillatory activity
      would provide information on the time courses and connectivity patterns of these
      activations. Following a paradigm previously assessed with
      electroencephalography, 16 adults were presented four types of stimuli at equal
      probabilities: illusory (Kanizsa) triangles, real triangles, no-triangle stimuli
      with rotated inducer disks, and curved illusory triangles serving as targets that
      subjects had to respond to. Induced oscillatory responses were compared between
      illusory triangles and no-triangle stimuli and between illusory and real
      triangles using a statistical probability mapping method. Illusory triangles were
      distinguished from no-triangles by increased activity at around 70 Hz over
      midline occipital cortex peaking at 240 ms after stimulus onset. This was
      followed by activations over bilateral lateral occipital areas at 430 ms.
      Illusory triangles differed from real triangles by increased spectral activity at
      90 Hz over posterior parietal cortex between 100 and 450 ms after stimulus onset,
      suggesting an involvement of visual dorsal stream regions. Coherence analysis
      showed increased connectivity between posterior parietal and lateral occipital
      cortex. These findings suggest that illusory triangles are encoded in parallel by
      networks along the visual ventral and dorsal streams.

PMID- 15488406
TI  - Modulation of motor-cortex oscillatory activity by painful Adelta- and C-fiber
      stimuli.
AB  - Spontaneous approximately 20-Hz oscillations, arising predominantly from the
      primary motor cortex (MI), are readily observed by magnetoencephalography (MEG).
      Prior studies have indicated that the level of the approximately 20-Hz rhythm
      reflects the functional state of the MI cortex: increased 20-Hz level is
      associated with increased inhibition and suppression of the rhythm with
      excitation of MI. Close interaction is suggested between pain and the motor
      system by the association of chronic pain with motor dysfunction and by the
      alleviation of pain by motor-cortex stimulation. We therefore explored the effect
      of noxious input on motor-cortex functions by recording MEG signals from nine
      healthy subjects during selective laser stimulation of Adelta- and C-fibers of
      the hand. The approximately 20-Hz level was suppressed in the contralateral MI
      cortex in all nine subjects after painful Adelta- and C-fiber stimuli (P <
      0.001). The suppression started 180 +/- 10 ms (mean +/- SEM) after Adelta-fiber
      stimuli and 820 +/- 30 ms after C-fiber stimuli, and peaked 160-170 ms later.
      Similar, but about 50% weaker, suppression of the approximately 20-Hz
      oscillations occurred in seven out of nine subjects in the ipsilateral MI. These
      results suggest automatic, lateralized, excitation of the MI cortex by noxious
      Adelta- and C-fiber input.

PMID- 15488407
TI  - Differentiating AD from aging using semiautomated measurement of hippocampal
      atrophy rates.
AB  - Manual segmentation of the hippocampus is the gold standard in volumetric
      hippocampal magnetic resonance imaging (MRI) analysis; however, this is difficult
      to achieve reproducibly. This study explores whether application of local
      registration and calculation of the hippocampal boundary shift integral (HBSI)
      can reduce random variation compared with manual measures. Hippocampi were
      outlined on the baseline and registered-repeat MRIs of 32 clinically diagnosed
      Alzheimer's disease (AD) patients and 47 matched controls (37-86 years) with a
      wide range of scanning intervals (175-1173 days). The scans were globally
      registered using 9 degrees of freedom and subsequently locally registered using 6
      degrees of freedom and HBSI was then calculated automatically. HBSI significantly
      reduced the mean rate (P < 0.01) and variation in controls (P < 0.001) and
      increased group separation between AD cases and controls. When comparing HBSI
      atrophy rates with manually derived atrophy rates at 90% sensitivity,
      specificities were 98% and 81%, respectively. From logistic regression models, a
      1% increase in HBSI atrophy rates was associated with an 11-fold (CI 3, 36)
      increase in the odds of a diagnosis of AD. For manually derived atrophy rates,
      the equivalent odds ratio was 3 (CI 2,4). We conclude that HBSI-derived atrophy
      rates reduce operator time and error, and are at least as effective as the manual
      equivalent as a diagnostic marker and are a potential marker of progression in
      longitudinal studies and trials.

PMID- 15488409
TI  - Is left inferior frontal gyrus a general mechanism for selection?
AB  - Converging lines of research in neuroimaging recognize selection as one of the
      critical functions of prefrontal cortex (e.g., see Annu. Rev. Neurosci. 24, 2001
      167). We examined a central thesis of a selection hypothesis (Neuropsychologia
      41, 2003 280) that the left inferior frontal gyrus (LIFG) serves as a general
      mechanism for selecting among competing representations (Annu. Rev. Neurosci. 18,
      1995 193). Participants were presented with two sets of letters to remember and
      then cued to select one set from the two as the target set for subsequent
      recognition. LIFG showed significantly more activation when the cue elicited a
      strong need for selection, relative to when it did not, suggesting that the
      involvement of this area in selection is generalizable beyond semantic retrieval
      tasks as originally found. This result provides supporting evidence for the
      selection hypothesis.

PMID- 15488408
TI  - Spectral spatiotemporal imaging of cortical oscillations and interactions in the
      human brain.
AB  - This paper presents a computationally efficient source estimation algorithm that
      localizes cortical oscillations and their phase relationships. The proposed
      method employs wavelet-transformed magnetoencephalography (MEG) data and uses
      anatomical MRI to constrain the current locations to the cortical mantle. In
      addition, the locations of the sources can be further confined with the help of
      functional MRI (fMRI) data. As a result, we obtain spatiotemporal maps of
      spectral power and phase relationships. As an example, we show how the phase
      locking value (PLV), that is, the trial-by-trial phase relationship between the
      stimulus and response, can be imaged on the cortex. We apply the method to
      spontaneous, evoked, and driven cortical oscillations measured with MEG. We test
      the method of combining MEG, structural MRI, and fMRI using simulated cortical
      oscillations along Heschl's gyrus (HG). We also analyze sustained auditory gamma
      band neuromagnetic fields from MEG and fMRI measurements. Our results show that
      combining the MEG recording with fMRI improves source localization for the non
      noise-normalized wavelet power. In contrast, noise-normalized spectral power or
      PLV localization may not benefit from the fMRI constraint. We show that if the
      thresholds are not properly chosen, noise-normalized spectral power or PLV
      estimates may contain false (phantom) sources, independent of the inclusion of
      the fMRI prior information. The proposed algorithm can be used for evoked MEG/EEG
      and block-designed or event-related fMRI paradigms, or for spontaneous MEG data
      sets. Spectral spatiotemporal imaging of cortical oscillations and interactions
      in the human brain can provide further understanding of large-scale neural
      activity and communication between different brain regions.

PMID- 15488410
TI  - Cognitive control in the posterior frontolateral cortex: evidence from common
      activations in task coordination, interference control, and working memory.
AB  - Cognitive control has often been associated with activations of middorsolateral
      prefrontal cortex. However, recent evidence highlights the importance of a more
      posterior frontolateral region around the junction of the inferior frontal sulcus
      and the inferior precentral sulcus (the inferior frontal junction area, IFJ). In
      the present experiment, we investigated the involvement of the IFJ in a task
      switching paradigm, a manual Stroop task, and a verbal n-back task in a within
      session within-group design. After computing contrasts for the individual tasks,
      the resulting z maps were overlaid to identify areas commonly activated by these
      tasks. Common activations were found in the IFJ, in the pre-SMA extending into
      mesial BA 8, in the middle frontal gyrus bordering the inferior frontal sulcus,
      in the anterior insula, and in parietal and thalamic regions. These results
      indicate the existence of a network of prefrontal, parietal, and subcortical
      regions mediating cognitive control in task coordination, interference control,
      and working memory. In particular, the results provide evidence for the
      assumption that, in the frontolateral cortex, not only the middorsolateral region
      but also the IFJ plays an important role in cognitive control.

PMID- 15488411
TI  - Hypercapnic normalization of BOLD fMRI: comparison across field strengths and
      pulse sequences.
AB  - The blood oxygenation level-dependent (BOLD) functional magnetic resonance
      imaging (fMRI) signal response to neural stimulation is influenced by many
      factors that are unrelated to the stimulus. These factors are physiological, such
      as the resting venous cerebral blood volume (CBV(v)) and vessel size, as well as
      experimental, such as pulse sequence and static magnetic field strength (B(0)).
      Thus, it is difficult to compare task-induced fMRI signals across subjects, field
      strengths, and pulse sequences. This problem can be overcome by normalizing the
      neural activity-induced BOLD fMRI response by a global hypercapnia-induced BOLD
      signal. To demonstrate the effectiveness of the BOLD normalization approach,
      gradient-echo BOLD fMRI at 1.5, 4, and 7 T and spin-echo BOLD fMRI at 4 T were
      performed in human subjects. For neural stimulation, subjects performed
      sequential finger movements at 2 Hz, while for global stimulation, subjects
      breathed a 5% CO(2) gas mixture. Under all conditions, voxels containing
      primarily large veins and those containing primarily active tissue (i.e.,
      capillaries and small veins) showed distinguishable behavior after hypercapnic
      normalization. This allowed functional activity to be more accurately localized
      and quantified based on changes in venous blood oxygenation alone. The normalized
      BOLD signal induced by the motor task was consistent across different magnetic
      fields and pulse sequences, and corresponded well with cerebral blood flow
      measurements. Our data suggest that the hypercapnic normalization approach can
      improve the spatial specificity and interpretation of BOLD signals, allowing
      comparison of BOLD signals across subjects, field strengths, and pulse sequences.
      A theoretical framework for this method is provided.

PMID- 15488412
TI  - A meta-algorithm for brain extraction in MRI.
AB  - Accurate identification of brain tissue and cerebrospinal fluid (CSF) in a whole
      head MRI is a critical first step in many neuroimaging studies. Automating this
      procedure can eliminate intra- and interrater variance and greatly increase
      throughput for a labor-intensive step. Many available procedures perform
      differently across anatomy and under different acquisition protocols. We
      developed the Brain Extraction Meta-Algorithm (BEMA) to address these concerns.
      It executes many extraction algorithms and a registration procedure in parallel
      to combine the results in an intelligent fashion and obtain improved results over
      any of the individual algorithms. Using an atlas space, BEMA performs a voxelwise
      analysis of training data to determine the optimal Boolean combination of
      extraction algorithms to produce the most accurate result for a given voxel. This
      allows the provided extractors to be used differentially across anatomy,
      increasing both the accuracy and robustness of the procedure. We tested BEMA
      using modified forms of BrainSuite's Brain Surface Extractor (BSE), FSL's Brain
      Extraction Tool (BET), AFNI's 3dIntracranial, and FreeSurfer's MRI Watershed as
      well as FSL's FLIRT for the registration procedure. Training was performed on T1
      weighted scans of 136 subjects from five separate data sets with different
      acquisition parameters on separate scanners. Testing was performed on 135
      separate subjects from the same data sets. BEMA outperformed the individual
      algorithms, as well as interrater results from a subset of the scans, when
      compared for the mean Dice coefficient, a rating of the similarity of output
      masks to the manually defined gold standards.

PMID- 15488413
TI  - High-resolution mapping of neuronal activity by thallium autometallography.
AB  - Different methods are available for imaging neuronal activity in the mammalian
      brain with a spatial resolution sufficiently high to detect activation patterns
      at the level of individual functional modules such as cortical columns. Severe
      difficulties exist, however, in visualizing the different degree of activity of
      each individual neuron within such a module, and mapping neuronal activity with a
      spatial resolution of single axons has remained impossible thus far. Here, we
      present a novel method for mapping neuronal activity that is able to visualize
      activation patterns with light and electron microscopical resolution. The method
      is based on the tight coupling of neuronal activity and potassium (K(+)) uptake.
      We have injected Mongolian gerbils with the K(+) analogue thallium (Tl(+)),
      stimulated the animals with pure tones of different frequencies and analyzed, by
      an autometallographic method, the Tl(+) distribution in the auditory cortex (AC).
      We find tonotopically organized columns of increased Tl(+)-uptake in AC. Within
      columns, the spatial patterns of neuronal activity as revealed by thallium
      autometallography are highly elaborated. Tl(+)-uptake differs in different
      layers, sublayers, and cell types, being especially high in large multipolar
      inhibitory interneurons in layer IV. A prominent feature of the columnar
      activation pattern is the presence of vertical modules of minicolumnar
      dimensions. Clusters of layer Vb pyramidal cells and their apical dendrite
      bundles are clearly visible in the center of the columns.

PMID- 15488414
TI  - Automated morphometric study of brain variation in XXY males.
AB  - This paper studies brain morphometry variation associated with XXY males
      (Klinefelter's syndrome) by using an automated whole-brain volumetric analysis
      method. The application to 34 XXY males and 62 normal male controls reveals
      pronounced volume reduction in the brains of XXY males, relative to the brains of
      normal controls, localized at the insula, temporal gyri, amygdala, hippocampus,
      cingulate, and occipital gyri. Most of these statistically significant regions
      are in the gray matter structures, with the exception of one cluster of atrophy
      involved in white matter structure, i.e., right parietal lobe white matter.
      Compared to previous findings documented in the literature, our findings provide
      a better spatial localization of the affected regions. In addition to the
      reduction of local volume, overall enlargement of ventricles and overall volume
      reduction of both white matter and gray matter are also found in XXY males.

PMID- 15488415
TI  - Multigrid priors for a Bayesian approach to fMRI.
AB  - We introduce multigrid priors to construct a Bayesian-inspired method to asses
      brain activity in functional magnetic resonance imaging (fMRI). A sequence of
      different scale grids is constructed over the image. Starting from the finest
      scale, coarse grain data variables are sequentially defined for each scale. Then
      we move back to finer scales, determining for each coarse scale a set of
      posterior probabilities. The posterior on a coarse scale is used as the prior for
      activity at the next finer scale. To test the method, we use a linear model with
      a given hemodynamic response function to construct the likelihood. We apply the
      method both to real and simulated data of a boxcar experiment. To measure the
      number of errors, we impose a decision to determine activity by setting a
      threshold on the posterior. Receiver operating characteristic (ROC) curves are
      used to study the dependence on threshold and on a few hyperparameters in the
      relation between specificity and sensitivity. We also study the deterioration of
      the results for real data, under information loss. This is done by decreasing the
      number of images in each period and also by decreasing the signal to noise ratio
      and compare the robustness to other methods.

PMID- 15488416
TI  - Voxel-based morphometry detects patterns of atrophy that help differentiate
      progressive supranuclear palsy and Parkinson's disease.
AB  - Progressive supranuclear palsy (PSP) and Parkinson's disease (PD) are
      neurodegenerative diseases with distinctive pathological appearances. Early
      clinical diagnosis can be difficult. MRI may help differentiate PSP from PD, but
      the differences are often only obvious with advanced disease. It would be useful
      to have an unbiased assessment of difference to guide visual assessment of MRI as
      an aid to clinical diagnosis. Voxel-based morphometry (VBM) offers nonbiased,
      observer-independent morphometric MRI analysis. Our objectives were to assess
      structural differences between PSP, PD, and normal controls and test the clinical
      utility of the results. T1-weighted MR images in 12 patients with clinically
      diagnosed PSP, 12 with PD, and 12 age- and sex-matched controls were normalized
      to a common stereotaxic space and segmented into gray matter (GM) and white
      matter (WM) then analyzed using VBM. MRI scans were reviewed by a
      neuroradiologist blinded to the clinical diagnosis and assigned to the "non-PSP"
      or "PSP" group based on regional differences highlighted using VBM. VBM revealed
      significant group differences between PSP and PD as well as PSP and controls,
      with tissue reduction demonstrated in the region of the cerebral peduncles and
      midbrain. With these regional differences as a guide, neuroradiological diagnosis
      achieved a sensitivity of 83% and a specificity of 79%. VBM did not detect
      dramatic changes in frontal regions despite significant frontal cognitive decline
      in the PSP group. Pathology in the basal ganglia rather than tissue loss in the
      frontal lobes could be responsible for this. This information may help in the
      differentiation of PSP in clinical practice.

PMID- 15488417
TI  - Cooperation of the anterior cingulate cortex and dorsolateral prefrontal cortex
      for attention shifting.
AB  - Attention shifting in the working memory system plays an important role in goal
      oriented behavior, such as reading, reasoning, and driving, because it involves
      several cognitive processes. This study identified brain activity leading to
      individual differences in attention shifting for dual-task performance by using
      the group comparison approach. A large-scale pilot study was initially conducted
      to select suitable good and poor performers. The fMRI experiment consisted of a
      dual-task condition and two single-task conditions. Under the dual-task
      condition, participants verified the status of letters while concurrently
      retaining arrow orientations. The behavioral results indicated that accuracy in
      arrow recognition was better in the good performers than in the poor performers
      under the dual-task condition but not under the single-task condition. Dual-task
      performance showed a positive correlation with mean signal change in the right
      anterior cingulate cortex (ACC) and right dorsolateral prefrontal cortex (DLPFC).
      Structural equation modeling indicated that effective connectivity between the
      right ACC and right DLPFC was present in the good performers but not in the poor
      performers, although activations of the task-dependent posterior regions were
      modulated by the right ACC and right DLPFC. We conclude that individual
      differences in attention shifting heavily depend on the functional efficiency of
      the cingulo-prefrontal network.

PMID- 15488418
TI  - fMRI activation maps based on the NN-ARx model.
AB  - The most significant progresses in the understanding of human brain functions
      have been possible due to the use of functional magnetic resonance imaging
      (fMRI), which when used in combination with other standard neuroimaging
      techniques (i.e., EEG) provides researchers with a potential tool to elucidate
      many biophysical principles, established previously by animal comparative
      studies. However, to date, most of the methods proposed in the literature seeking
      fMRI signs have been limited to the use of a top-down data analysis approach,
      thus ignoring a pool of physiological facts. In spite of the important
      contributions achieved by applying these methods to actual data, there is a
      disproportionate gap between theoretical models and data-analysis strategies
      while trying to focus on several new prospects, like for example fMRI/EEG data
      fusion, causality/connectivity patterns, and nonlinear BOLD signal dynamics. In
      this paper, we propose a new approach which will allow many of the abovementioned
      hot topics to be addressed in the near future with an underlying interpretability
      based on bottom-up modeling. In particular, the theta-MAP presented in the paper
      to test brain activation corresponds very well with the standardized t test of
      the SPM99 toolbox. Additionally, a new Impulse Response Function (IRF) has been
      formulated, directly related to the well-established concept of the hemodynamics
      response function (HRF). The model uses not only the information contained in the
      signal but also that in the structure of the background noise to simultaneously
      estimate the IRF and the autocorrelation function (ACF) by using an
      autoregressive (AR) model with a filtered Poisson process driving the dynamics.
      The short-range contributions of voxels within the near-neighborhood are also
      included, and the potential drift was characterized by a polynomial series. Since
      our model originated from an immediate extension of the hemodynamics approach
      [Friston, K.J., Mechelli, A., Turner, R., Price C.J. (2000a). Nonlinear responses
      in fMRI: the balloon model, volterra kernels, and other hemodynamics. NeuroImage
      12, 466-477.], a natural interpretability of the results is feasible.

PMID- 15488419
TI  - Cerebral regions and hemispheric specialization for processing spatial
      frequencies during natural scene recognition. An event-related fMRI study.
AB  - It has been suggested that visual scene recognition is mainly based on spatial
      frequency (Fourier) analysis of the image. This analysis starts with processing
      low spatial frequencies (LSF), followed by processing high spatial frequencies
      (HSF). Within the framework of the spatial frequency analysis, the right/left
      hemisphere would be predominantly involved in LSF/HSF analysis, respectively. The
      aim of this event-related fMRI study was to evaluate neural correlates and
      hemispheric specialization of spatial frequency analysis during recognition of
      nonfiltered (NF) and filtered, either in LSF or HSF, natural scenes. Comparing
      LSF or NF to HSF scene recognition, significant activation was obtained within
      right anterior temporal cortex and right parahippocampal gyrus. As these regions
      are known to be involved in scene processing, we interpret this result as
      suggesting that scene recognition is mainly based on LSF extraction and analysis.
      When LSF scene was compared to HSF scene recognition, supplementary activation
      was obtained within the right inferior parietal lobule that likely reflects
      attentional modulation on spatial frequency processing. A direct interhemispheric
      comparison for each particular band of spatial frequencies highlighted
      predominance within the early visual areas (such as the middle occipital gyrus)
      to the right for LSF processing and to the left for HSF processing. This result
      provides supplementary evidence for hemispheric specialization at early levels of
      visual analysis when spatial frequencies are processed.

PMID- 15488420
TI  - Global and local gray matter loss in mild cognitive impairment and Alzheimer's
      disease.
AB  - PURPOSE: Mild cognitive impairment (MCI) is thought to be the prodromal phase to
      Alzheimer's disease (AD). We analyzed patterns of gray matter (GM) loss to
      examine what characterizes MCI and what determines the difference with AD.
      MATERIALS AND METHODS: Thirty-three subjects with AD, 14 normal elderly controls
      (NCLR), and 22 amnestic MCI subjects were included and underwent brain MR
      imaging. Global GM volume was assessed using segmentation and local GM volume was
      assessed using voxel-based morphometry (VBM); VBM was optimized for template
      mismatch and statistical mass. RESULTS: AD subjects had significantly (12.3%)
      lower mean global GM volume when compared to controls (517 +/- 58 vs. 590 +/- 52
      ml; P < 0.001). Global GM volume in the MCI group (552 +/- 52) was intermediate
      between these two: 6.2% lower than AD and 6.5% higher than the controls but not
      significantly different from either group. VBM showed that subjects with MCI had
      significant local reductions in gray matter in the medial temporal lobe (MTL),
      the insula, and thalamus compared to NCLR subjects. By contrast, when compared to
      subjects with AD, MCI subjects had more GM in the parietal association areas and
      the anterior and the posterior cingulate. CONCLUSION: GM loss in the MTL
      characterizes MCI, while GM loss in the parietal and cingulate cortices might be
      a feature of AD.

PMID- 15488421
TI  - Whole-brain voxel-based statistical analysis of gray matter and white matter in
      temporal lobe epilepsy.
AB  - Volumetric MRI studies based on manual labeling of selected anatomical structures
      have provided in vivo evidence that brain abnormalities associated with temporal
      lobe epilepsy (TLE) extend beyond the hippocampus. Voxel-based morphometry (VBM)
      is a fully automated image analysis technique allowing identification of regional
      differences in gray matter (GM) and white matter (WM) between groups of subjects
      without a prior region of interest. The purpose of this study was to determine
      whole-brain GM and WM changes in TLE and to investigate the relationship between
      these abnormalities and clinical parameters. We studied 85 patients with
      pharmacologically intractable TLE and unilateral hippocampal atrophy and 47 age-
      and sex-matched healthy control subjects. The seizure focus was right sided in 40
      patients and left sided in 45. Student's t test statistical maps of differences
      between patients' and controls' GM and WM concentrations were obtained using a
      general linear model. A further regression against duration of epilepsy, age of
      onset, presence of febrile convulsions, and secondary generalized seizures was
      performed with the TLE population. Voxel-based morphometry revealed that GM
      pathology in TLE extends beyond the hippocampus involving other limbic areas such
      as the cingulum and the thalamus, as well as extralimbic areas, particularly the
      frontal lobe. White matter reduction was found only ipsilateral to the seizure
      focus, including the temporopolar, entorhinal, and perirhinal areas. This pattern
      of structural changes is suggestive of disconnection involving preferentially
      frontolimbic pathways in patients with pharmacologically intractable TLE.

PMID- 15488422
TI  - A unified approach for morphometric and functional data analysis in young, old,
      and demented adults using automated atlas-based head size normalization:
      reliability and validation against manual measurement of total intracranial
      volume.
AB  - Atlas normalization, as commonly used by functional data analysis, provides an
      automated solution to the widely encountered problem of correcting for head size
      variation in regional and whole-brain morphometric analyses, so long as an age-
      and population-appropriate target atlas is used. In the present article, we
      develop and validate an atlas normalization procedure for head size correction
      using manual total intracranial volume (TIV) measurement as a reference. The
      target image used for atlas transformation consisted of a merged young and old
      adult template specifically created for cross age-span normalization. Automated
      atlas transformation generated the Atlas Scaling Factor (ASF) defined as the
      volume-scaling factor required to match each individual to the atlas target.
      Because atlas normalization equates head size, the ASF should be proportional to
      TIV. A validation analysis was performed on 147 subjects to evaluate ASF as a
      proxy for manual TIV measurement. In addition, 19 subjects were imaged on
      multiple days to assess test-retest reliability. Results indicated that the ASF
      was (1) equivalent to manual TIV normalization (r = 0.93), (2) reliable across
      multiple imaging sessions (r = 1.00; mean absolute percentage of difference =
      0.51%), (3) able to connect between-gender head size differences, and (4)
      minimally biased in demented older adults with marked atrophy. Hippocampal volume
      differences between nondemented (n = 49) and demented (n = 50) older adults
      (measured manually) were equivalent whether corrected using manual TIV or
      automated ASF (effect sizes of 1.29 and 1.46, respectively). To provide normative
      values, ASF was used to automatically derive estimated TIV (eTIV) in 335 subjects
      aged 15-96 including both clinically characterized nondemented (n = 77) and
      demented (n = 90) older adults. Differences in eTIV between nondemented and
      demented groups were negligible, thus failing to support the hypothesis that
      large premorbid brain size moderates Alzheimer's disease. Gender was the only
      robust factor that influenced eTIV. Men showed an approximately approximately 12%
      larger eTIV than women. These results demonstrate that atlas normalization using
      appropriate template images provides a robust, automated method for head size
      correction that is equivalent to manual TIV correction in studies of aging and
      dementia. Thus, atlas normalization provides a common framework for both
      morphometric and functional data analysis.

PMID- 15488423
TI  - Contrasting metabolic impairment in frontotemporal degeneration and early onset
      Alzheimer's disease.
AB  - [18F]FDG positron emission tomography (PET) scans of 14 patients comprising the
      clinical prototypes of dementias that are considered to be associated with
      frontotemporal lobar degeneration (FTLD) were compared to a population of 15
      patients with early onset Alzheimer's disease (EOAD). The FTLD group included
      patients with frontotemporal dementia (FTD), semantic dementia (SD), and primary
      progressive aphasia (PPA). A voxel to voxel group comparison identified metabolic
      impairment in the bilateral ventromedial frontal area, the left anterior insula,
      and inferior frontal cortex, and indicated the right middle temporal gyrus to
      exhibit increased activity in FTLD compared to EOAD patients. All identified
      cortical structures are considered to be critically involved in
      neuropsychological features associated with FTLD (altered social behavior,
      aphasia) and EOAD (impaired linguistic and visuo-constructive abilities). In
      conjunction with recent insights from neuropathologic investigations, these
      results implicate that the a priori heterogeneous prototypes of FTLD (FTD, SD,
      PPA) may share more common ground than previously assumed, and therefore would
      become distinguishable as an entire group from EOAD.

PMID- 15488424
TI  - The neural bases of cooperation and competition: an fMRI investigation.
AB  - Cooperation and competition are two basic modes of social cognition that
      necessitate monitoring of both one's own and others' actions, as well as adopting
      a specific mental set. In this fMRI, study individuals played a specially
      designed computer game, according to a set of predefined rules, either in
      cooperation with or in competition against another person. The hemodynamic
      response during these conditions was contrasted to that of the same subjects
      playing the game independently. Both cooperation and competition stances resulted
      in activation of a common frontoparietal network subserving executive functions,
      as well as the anterior insula, involved in autonomic arousal. Moreover, distinct
      regions were found to be selectively associated with cooperation and competition,
      notably the orbitofrontal cortex in the former and the inferior parietal and
      medial prefrontal cortices in the latter. This pattern reflects the different
      mental frameworks implicated in being cooperative versus competitive with another
      person. In accordance with evidence from evolutionary psychology as well as from
      developmental psychology, we argue that cooperation is a socially rewarding
      process and is associated with specific left medial orbitofrontal cortex
      involvement.

PMID- 15488425
TI  - Measuring functional connectivity during distinct stages of a cognitive task.
AB  - The inherently multivariate nature of functional brain imaging data affords the
      unique opportunity to explore how anatomically disparate brain areas interact
      during cognitive tasks. We introduce a new method for characterizing inter
      regional interactions using event-related functional magnetic resonance imaging
      (fMRI) data. This method's principle advantage over existing analytical
      techniques is its ability to model the functional connectivity between brain
      regions during distinct stages of a cognitive task. The method is implemented by
      using separate covariates to model the activity evoked during each stage of each
      individual trial in the context of the general linear model (GLM). The resulting
      parameter estimates (beta values) are sorted according to the stage from which
      they were derived to form a set of stage-specific beta series. Regions whose beta
      series are correlated during a given stage are inferred to be functionally
      interacting during that stage. To validate the assumption that correlated
      fluctuations in trial-to-trial beta values imply functional connectivity, we
      applied the method to an event-related fMRI data set in which subjects performed
      two sequence-tapping tasks. In concordance with previous electrophysiological and
      fMRI coherence studies, we found that the task requiring greater bimanual
      coordination induced stronger correlations between motor regions of the two
      hemispheres. The method was then applied to an event-related fMRI data set in
      which subjects performed a delayed recognition task. Distinct functional
      connectivity maps were generated during the component stages of this task,
      illustrating how important and novel observations of neural networks within the
      isolated stages of a cognitive task can be obtained.

PMID- 15488426
TI  - Spatiotemporal analysis of event-related fMRI data using partial least squares.
AB  - Partial least squares (PLS) has proven to be a important multivariate analytic
      tool for positron emission tomographic and, more recently, event-related
      potential (ERP) data. The application to ERP incorporates the ability to analyze
      space and time together, a feature that has obvious appeal for event-related
      functional magnetic resonance imaging (fMRI) data. This paper presents the
      extension of spatiotemporal PLS (ST-PLS) to fMRI, explaining the theoretical
      foundation and application to an fMRI study of auditory and visual perceptual
      memory. Analysis of activation effects with ST-PLS was compared with conventional
      univariate random effects analysis, showing general consensus for both methods,
      but several unique observations by ST-PLS, including enhanced statistical power.
      The application of ST-PLS for assessment of task-dependent brain-behavior
      relationships is also presented. Singular features of ST-PLS include (1) no
      assumptions about the shape of the hemodynamic response functions (HRFs); (2)
      robust statistical assessment at the image level through permutation tests; (3)
      protection against outlier influences at the voxel level through bootstrap
      resampling; (4) flexible analytic configurations that allow assessment of
      activation difference, brain-behavior relations, and functional connectivity.
      These features enable ST-PLS to act as an important complement to other
      multivariate and univariate approaches used in neuroimaging research.

PMID- 15488427
TI  - Youth violence: opportunities for intervention.

PMID- 15488428
TI  - Are family meal patterns associated with disordered eating behaviors among
      adolescents?
AB  - PURPOSE: To examine associations between family meal patterns (frequency,
      priority, atmosphere, and structure of family meals) and disordered eating
      (unhealthy weight control behaviors, binge eating, and chronic dieting) in
      adolescent girls and boys. METHODS: Survey and anthropometric data were collected
      from 4746 ethnically diverse adolescents from public middle and senior high
      schools who participated in the Project EAT study (Eating Among Teens). Variables
      of interest included family meal patterns and disordered eating behaviors.
      Logistic regressions were performed to examine associations between family meal
      patterns and disordered eating behaviors adjusting for body mass index,
      sociodemographic characteristics, family connectedness, and weight pressures
      within the home. RESULTS: In general, adolescents who reported more frequent
      family meals, high priority for family meals, a positive atmosphere at family
      meals, and a more structured family meal environment were less likely to engage
      in disordered eating. For example, 18.1% of girls who reported 1-2 family
      meals/week engaged in extreme weight control behaviors compared with 8.8% of
      girls who reported 3-4 family meals/week. Making family meals a priority, in
      spite of scheduling difficulties, emerged as the most consistent protective
      factor for disordered eating. Associations between family meal patterns and
      disordered eating behaviors tended to be stronger among girls than among boys.
      Family meal patterns were more consistently associated with unhealthy weight
      control behaviors than with chronic dieting and binge eating. Although
      associations between family meals and disordered eating were weakened after
      adjusting for more global familial factors, including family connectedness and
      weight-specific pressures within the home, a number of the associations remained
      statistically significant, suggesting an independent relationship between family
      meals and disordered eating. CONCLUSION: Family meals have the potential to play
      an important role in the prevention of unhealthy weight control behaviors among
      youth. Findings suggest that attention needs to be directed toward increasing
      family meal frequency and creating a positive environment for family meals.

PMID- 15488429
TI  - Overweight and obesity in Canadian adolescents and their associations with
      dietary habits and physical activity patterns.
AB  - PURPOSE: To present recent overweight and obesity prevalence rates for 11-16-year
      old Canadian youth and to examine associations between overweight and obesity
      with dietary habits and leisure-time physical activities. METHODS: Nationally
      representative sample of 11-16-year-old adolescents (n = 5890) from the Canadian
      component of the 2001/02 World Health Organization Health Behaviour in School
      Aged Children Survey were used. Height, weight, dietary habits, and leisure-time
      activities were determined from self-report. Age- and gender-specific prevalence
      rates of overweight and obesity were calculated based on international body mass
      index cut-points. Logistic regression was employed to examine the association
      among measures of overweight, obesity, and lifestyle habits. RESULTS: Fifteen
      percent of 11-16-year-old Canadian youth were overweight (preobese) and 4.6% were
      obese in 2002. These prevalence rates were greater in boys than girls (p < .001),
      but did not vary according to age. There were no clear associations observed
      between dietary habits and measures of overweight and obesity. However, physical
      activity levels were lower (p < or = .05) and television viewing times were
      higher (p < .01) in overweight and obese boys and girls than normal-weight youth.
      CONCLUSIONS: The prevalence rates of overweight and obesity in Canadian youth are
      high. The results suggest that physical inactivity and sedentary behaviors are
      strongly related to obesity in Canadian adolescents.

PMID- 15488430
TI  - Predictors for emotionally distressed adolescents to receive mental health care.
AB  - PURPOSE: To determine predictors for emotionally distressed adolescents from
      different racial/ethnic groups to receive psychological counseling. METHODS: This
      study used secondary database analysis of the restricted-use National
      Longitudinal Study of Adolescent Health, using predictor variables from Wave 1
      and the outcome variable from Wave 2. Adolescents scoring in the top third of an
      emotional distress scale (n = 3963) were analyzed by race/ethnicity. Multivariate
      analyses were based on the access-to-care model. RESULTS: Emotionally distressed
      Blacks reported receiving psychological counseling significantly less than Whites
      and Hispanics (8% vs. 19% and 16%, respectively). The most important factors
      associated with receiving counseling for each racial/ethnic group were: Whites (n
      = 1681): suicidality and urban area, [Adjusted odds ratio (AOR) 1.9, 95th
      confidence interval (CI) (1.4, 2.6)] and [AOR 1.4, 95th CI, 95th CI (1.0, 1.8)],
      respectively; Blacks (n = 677): urban area [AOR 2.9, 95th CI (1.4, 6.0)];
      Hispanics (n = 5326): suicidality and barriers to care, [AOR 2.2, 95th CI (1.0,
      4.7)] and [AOR 0.4, 95th CI (0.2, 0.7)], respectively. CONCLUSIONS: Predictors
      for receiving counseling varied for different racial and ethnic groups of
      adolescents. Even after adjusting for family income and parent education,
      distressed black adolescents were less likely to receive counseling. The findings
      specific to distressed black adolescents indicate that other factors may underlie
      differences in utilization of mental health services.

PMID- 15488431
TI  - Adolescent assessment of cardiovascular heart disease risk factor attitudes and
      habits.
AB  - PURPOSE: To assess the attitudes of adolescents regarding cardiovascular heart
      disease risk factors and determine their potential influence on reported habits:
      exercise, smoking, and diet, as well as their body mass index (BMI). METHODS:
      Surveys were distributed to 141 male and 207 female adolescents at two clinic
      sites that serve a mostly Medicaid or uninsured population. Attitudes for
      obesity, smoking, and high fat diet were assessed with Likert scales, and habits
      for exercise, smoking, and fast food consumption were self-reported. Height and
      weight data were collected as well. Univariate modeling was accomplished with
      Spearman's rank correlation coefficients, contingency table analysis, and ANOVA.
      Logistic regression was used for multivariate modeling. RESULTS: The majority of
      participants agreed that obesity, smoking, and high fat diets may lead to heart
      disease. Fifty percent of the population exercised three times or less a week.
      Reported smoking was similar to national averages and increased with age.
      Participant attitudes were disparate to their reported habits. Occurrence of
      obesity in the sample was higher than national averages. Smokers, compared with
      nonsmokers, were 1.9 times as likely to be overweight or obese (p = .05).
      Participants who had a parent/guardian or grandparent with a history of heart
      attacks were 2.7 times as likely to smoke (p = .001). CONCLUSION: Adolescents
      possess knowledge of cardiovascular risk factors as reflected in their attitude
      assessments; however, their lifestyle choices contradict these beliefs.

PMID- 15488432
TI  - It's not what you say, it's how many different ways you can say it: links between
      divergent peer resistance skills and delinquency a year later.
AB  - PURPOSE: To examine whether generation of 'socially appropriate' responses or
      divergent responses to continued peer pressure is a more effective deterrent of
      actual delinquency. METHODS: The sample of 129 urban adolescents included both
      boys and girls (51.9% male) and was predominantly black (48.%) and Hispanic
      (28.7%). They were studied longitudinally from seventh to eighth grade in New
      York City from 2000-2001. Resistance strategies to offers to smoke and to
      shoplift were assessed in two separate videotaped role-plays. Socially
      appropriate responses were defined as assertive and nonaggressive, including the
      use of a simple no; direct, declarative statements; and offering prosocial
      alternatives. Divergent responses were defined as multiple unique response types
      within the same situation regardless of appropriateness. Data were analyzed using
      hierarchical logistic regressions. RESULTS: High use of divergent responses was
      consistently associated favorably with changes in delinquency from seventh to
      eighth grade. High use of divergent responses was associated with lowered
      likelihood to vandalize, steal or shoplift, and commit multiple acts of any type
      of delinquency, even after controlling for seventh grade delinquency. Socially
      appropriate responses showed little association to any delinquent behavior.
      CONCLUSIONS: Different social pressure situations and contexts may require
      different responses. As trying to teach effective responses for every single
      potential peer pressure situation would be impossible, promoting divergent
      thinking may be an attractive alternative.

PMID- 15488433
TI  - Perfectionism dimensions in children and adolescents with anorexia nervosa.
AB  - PURPOSE: To assess the dimensions of perfectionism in adolescents with anorexia
      nervosa in comparison with adolescents from the general population and to
      validate the Spanish versions of two measures of perfectionism. METHODS: The
      Child and Adolescents Perfectionism Scale (CAPS), the Perfectionistic Self
      Presentation Scale (PSPS) scale, the Eating Attitudes Test (EAT), and the Beck
      Depression Inventory (BDI) were administered to a group of 71 anorexia nervosa
      patients (mean age 15.3 years). Moreover, the CAPS and the PSPS were also
      administered to 113 adolescents from the general population (mean age 14.6
      years). The CAPS and the PSPS were administered again after 1 week in 68 subjects
      to evaluate test-retest reliability. RESULTS: Both the CAPS and the PSPS
      demonstrated good internal consistency (Cronbach alpha for anorexia nervosa
      patients = .91; Cronbach alpha for general population = .85) and the two scales
      of the CAPS also had alpha coefficients in excess of .7. One-week test-retest
      reliability was also adequate (r = .80). Anorexia nervosa patients had higher
      mean scores in Self-oriented perfectionism (p < .001) and Perfectionistic self
      presentation (p < .001) but not in Socially prescribed perfectionism (p = .292).
      There were significant correlations among perfectionism and the EAT and the BDI.
      A percentage of anorexia nervosa patients between 39% and 42% obtained a score
      higher than the mean in the comparison group plus two standard deviations in Self
      oriented perfectionism and Perfectionistics self-presentation. CONCLUSIONS: The
      Spanish version of the CAPS and the PSPS showed good psychometric properties. A
      percentage of 40% of adolescent patients with anorexia nervosa show high Self
      oriented perfectionism and Perfectionistic self-presentation.

PMID- 15488434
TI  - Reading nutrition labels and fat consumption in adolescents.
AB  - We studied the relationship between reading nutrition labels and percent calorie
      intake from fat. In adolescent boys, reading nutrition labels was associated with
      higher fat intake. In girls, fat intake did not differ by frequency of nutrition
      label reading. Nutrition label reading does not translate into healthier diet in
      adolescents.

PMID- 15488435
TI  - The health of young people in a global context.
AB  - PURPOSE: To examine the chief causes and influences of morbidity and mortality
      among young people throughout the world. METHODS: A comprehensive literature
      search was conducted that included WHO's Global Burden of Disease, UNFPA's State
      of the Worlds' Population, Medline, Popline, Sociological Abstracts, as well as
      data collected from UNICEF, UNAIDS, Population Reference Bureau, and the United
      Nations Headquarters. Experts in the fields of substance use, suicide, and
      infectious diseases were also contacted for unpublished and published sources.
      Studies were restricted to those completed after 1985, had a sample size of at
      least 100, focused primarily on the age group of 10-24 years, and examined trends
      related to unintentional injuries, HIV/AIDS, suicide, homicide, war, maternal
      mortality, pregnancy, abortion, sexually transmitted diseases, substance abuse,
      and infectious diseases. RESULTS: Trends in adolescent morbidity and mortality
      have shifted over the past decade from predominately infectious to social
      etiologies. Currently, unintentional injury is the leading killer of young people
      in nearly every region of the world, with homicide, war, and interpersonal
      violence following closely behind. CONCLUSIONS: The changes in population,
      migration, age of marriage, and education have had profound impact on the
      mortality and morbidity among adolescents. As we come to learn about the factors
      that influence adolescent morbidity and mortality, we begin to have a better
      understanding of how to improve the health of youth throughout the world.

PMID- 15488436
TI  - An exploration of the relationship between youth assets and engagement in risky
      sexual behaviors.
AB  - PURPOSE: To examine the relationship between specific youth assets and
      adolescents' engagement in risky sexual behaviors, as measured by an Aggregate
      Sexual Risk score, and to specifically explore which youth assets and demographic
      variables were predictive of youth engagement in risky sexual intercourse.
      METHODS: A total of 2108 sexually active high school students attending public
      high schools in a southern state completed a self-report questionnaire that
      measured youth assets. Based upon responses to items measuring risk behaviors, an
      Aggregate Sexual Risk score was calculated for each student. Unconditional
      logistic regression and multivariate logistic regression analyses were conducted
      to examine the relationships between the assets and the Aggregate Risk Score.
      Four separate analyses (white females, white males, black females, and black
      males) were conducted. RESULTS: In general, the patterns in all four groups
      indicated that students who had an Aggregate Risk Score of > or = 3 (high risk)
      possessed less of the measured youth assets. The assets that were most
      significantly associated with engagement in risky sexual behaviors included self
      peer values regarding risky behaviors, quantity of other adult support, and
      youths' empathetic relationships. Thus, students who reported not having these
      assets were significantly more likely to engage in the risky sexual behaviors.
      CONCLUSIONS: Results underscore the relationship of specific youth assets to
      sexual risk behaviors. Health researcher and practitioners who work to prevent
      teen pregnancy and sexually transmitted infections among teenagers need to
      understand and acknowledge these factors within this population so that the
      assets can be built or strengthened.

PMID- 15488437
TI  - Internet-initiated sex crimes against minors: implications for prevention based
      on findings from a national study.
AB  - PURPOSE: To describe the characteristics of episodes in which juveniles became
      victims of sex crimes committed by people they met through the Internet. METHODS:
      A national survey of a stratified random sample of 2574 law enforcement agencies
      conducted between October 2001 and July 2002. Telephone interviews were conducted
      with local, state, and federal law enforcement investigators concerning 129
      sexual offenses against juvenile victims that originated with online encounters.
      RESULTS: Victims in these crimes were primarily 13- through 15-year-old teenage
      girls (75%) who met adult offenders (76% older than 25) in Internet chat rooms.
      Most offenders did not deceive victims about the fact that they were adults who
      were interested in sexual relationships. Most victims met and had sex with the
      adults on more than one occasion. Half of the victims were described as being in
      love with or feeling close bonds with the offenders. Almost all cases with male
      victims involved male offenders. Offenders used violence in 5% of the episodes.
      CONCLUSIONS: Health care professionals and educators, parents and media need to
      be aware of the existence, nature and real life dynamics of these online
      relationships among adolescents. Information about Internet safety should include
      frank discussion about why these relationships are inappropriate, criminal, and
      detrimental to the developmental needs of youth.

PMID- 15488438
TI  - Youth violence perpetration: what protects? What predicts? Findings from the
      National Longitudinal Study of Adolescent Health.
AB  - PURPOSE: To identify individual, family and community-level risk and protective
      factors for violence perpetration in a national sample of adolescents. METHODS:
      Analysis of two waves of data from the National Longitudinal Study of Adolescent
      Health. The key outcome variable was Time 2 violence involvement, approximately 1
      year after initial data collection, measured by a validated scale of violence
      perpetration RESULTS: Controlling for demographic covariates in multivariate
      regression models, key Time 1 protective factors against Time 2 violence
      perpetration included measures related to parental expectations, connectedness
      with parents and other adults, and school, higher grade point average and
      religiosity. Significant predictive risk factors included a history of violence
      involvement and violence victimization, weapon carrying, school problems,
      substance use, health problems, and friend suicide. Probability profiles then
      assessed the ability of protective factors to offset known risk factors for
      violence. For both girls and boys there were substantial reductions in the
      percentage of youth involved in violence in the presence of protective factors,
      even with significant risk factors present. CONCLUSIONS: Findings support the
      utility of a dual strategy of reducing risk factors while enhancing protective
      factors in the lives of adolescents.

PMID- 15488439
TI  - Young adults in Massachusetts: who is at risk of being uninsured?
AB  - PURPOSE: To identify sociodemographic factors associated with being uninsured
      among young adults in a state sample (Massachusetts) and to examine the
      independent association of insurance status with the young adult's reporting no
      health maintenance visit (check-up) in the past 2 years or reporting an inability
      to afford needed health care in the last 12 months. METHODS: Secondary analysis
      of data from the Massachusetts Behavioral Risk Factor Surveillance System for the
      years 1998-2000. In this cross-sectional study, data were examined for 1673 19-
      to 24-years-olds who provided information on sociodemographic variables, health
      insurance status, perceived inability to afford care, and health care use.
      Multiple logistic regression was used to estimate the odds of being uninsured.
      Subsequently, multiple logistic regression was used to estimate the odds of
      having no check-up in the last 2 years and of reporting the inability to afford
      needed health care in the last year. RESULTS: 15% of young adults were uninsured,
      including 20% of males and 10% of females. For both genders, the adjusted odds of
      being uninsured were lower for students and higher for those with a household
      income between 15,000 dollars and 24,999 dollars. Uninsured young men, but not
      women, had significantly higher odds of not having a routine check-up in the last
      2 years. Uninsured young adults of both genders had significantly higher odds of
      reporting the inability to afford needed care in the past 12 months. CONCLUSIONS:
      Programs and policies that seek to reduce the rates of uninsured young adults
      should especially target males and nonstudents. Improving health insurance
      coverage, especially for young adult males, may be associated with improved
      preventive health care access.

PMID- 15488440
TI  - More normal than not: a qualitative assessment of the developmental experiences
      of gay male youth.
AB  - PURPOSE: To examine gay youth experiences within the context of normal adolescent
      development. METHODS: Thematic analyses of interviews with 13 self-identified gay
      male youth, aged 16-22 years, each reporting minimal sexual identity distress,
      were completed. Interviews focused on: (a) descriptions of developmental changes
      perceived to occur for all adolescents, (b) descriptions of the participants'
      developmental experience, and (c) participants' direct comparisons of their
      perceptions of gay and nongay developmental experience. Data were analyzed by two
      investigators who, after initial review of the interview transcripts, developed a
      unified coding template to permit systematic analysis of the transcripts for
      recurrent themes. RESULTS: (a) Few (2 of 13) participants reported overall
      developmental experience markedly different from nongay peers. (b) Peer
      interaction was seen as the domain most different from that of nongay peers. (c)
      Open gay self-identification altered, generally positively, all peer interaction.
      (d) Increased peer interaction enhanced maturity in other domains. (e) Family
      dynamics were not substantively altered by open gay self-identification. (f)
      Middle and high school were identified as relatively hostile environments in
      which to openly identify as gay, affecting the timing and the extent of self
      disclosure. (g) Developmental progress showed asynchrony across developmental
      domains. CONCLUSION: General developmental dysfunction is not inevitable for gay
      adolescents, nor is identifiable personal or family pathology directly related to
      sexual identity.

PMID- 15488441
TI  - Development of a scale to measure adolescents' beliefs and attitudes about
      postponing sexual initiation.
AB  - PURPOSE: To develop a scale to measure adolescent beliefs and attitudes about
      postponing sexual initiation (PSI). METHODS: A theory-based, 12-item scale
      measuring beliefs about PSI was developed and administered via a mailed
      questionnaire to those participants in an ongoing longitudinal cohort study of
      adolescents who had not yet initiated sexual intercourse. Internal consistency
      reliability, content validity, factorial validity, and construct validity were
      assessed using cross-sectional data. RESULTS: Mean age for boys was 14.4 (+/-
      1.6) years and for girls 14.3 (+/-1.6) years (range 11 to 19 years), and 93% of
      respondents were white. The beliefs about PSI rated as most important by both
      girls and boys were concern about pregnancy and sexually transmitted infection.
      Cronbach alpha for the scale was 0.83 for girls and 0.88 for boys. Exploratory
      factor analysis demonstrated that the items loaded on four factors consistent
      with the theoretical basis of the model and confirmatory factor analysis
      demonstrated good fit of the overall model. The PSI scale score was associated
      with hypothesized sociodemographic, psychological, and behavioral variables,
      supporting construct validity of the scale. A higher score was associated with
      female gender; age < or = 14 years; higher global and social self-esteem; more
      frequent attendance at religious services; less peer pressure to have sexual
      intercourse; nonuse of alcohol, illicit drugs, and cigarettes; and no intention
      to initiate sexual intercourse in the next year. CONCLUSIONS: The PSI scale
      demonstrated satisfactory psychometric properties. Future research is needed to
      evaluate the utility of this scale in predicting sexual initiation and in
      interventions aimed at postponing sexual initiation.

PMID- 15488442
TI  - Perfectionism, low self-esteem, and family factors as predictors of bulimic
      behavior.
AB  - A previous study found that self-reported body dissatisfaction, depression, and
      peer pressure to maintain a thin body shape were significant predictors of
      bulimic behavior in college women, but that family functioning was not a
      significant predictor [Eat. Behav. 2 (2001) 323]. The current study examined
      whether perfectionism, low self-esteem, and a more specific family variable-
      perceived pressure from the family to be thin--predicted any additional variance
      in eating-disordered behavior after significant variables from the previous study
      had been taken into account. As in the previous study, self-reported body
      dissatisfaction, depression, and peer pressure to maintain a thin body shape were
      significant predictors of bulimic behavior. Perceived weight-related pressure
      from the family was also a significant predictor. In contrast, high parental
      expectations were found to predict lower levels of bulimic behavior and to
      moderate the effects of peer influence on bulimic behavior. The variables found
      in this study to be related to bulimic behavior may be useful targets for
      clinical intervention for women with disturbed eating patterns.

PMID- 15488443
TI  - Social anxiety and agoraphobia in the eating disorders: associations with eating
      attitudes and behaviours.
AB  - BACKGROUND: While eating disorders have a high comorbidity with anxiety
      disorders, little is presently known about how anxiety links to eating attitudes
      and behaviours and other related characteristics of eating-disordered
      individuals. The present study aimed to determine whether social anxiety and
      agoraphobia in eating-disordered individuals are linked to different eating
      attitudes and behaviours and levels of ego functioning. METHOD: The participants
      were 70 women who met DSM-IV criteria for an eating disorder. The Eating Disorder
      Inventory (EDI) was used as a measure of eating attitudes and ego-functioning
      characteristics, while the Social Phobia and Anxiety Inventory (SPAI) was used as
      a measure of levels of social anxiety and agoraphobia. RESULTS: High scores on
      the eating attitude scales of the EDI were associated with higher levels of
      social anxiety in eating-disordered individuals. High scores on the ego
      dysfunction scales of the EDI were associated with higher levels of social
      anxiety and agoraphobia. CONCLUSIONS: The present findings suggest that eating
      related attitudes and behaviours are associated with high levels of social
      anxiety, while psychological characteristics not specifically related to eating
      are associated with anxiety more broadly. The results highlight the importance of
      identifying and addressing comorbid anxiety in eating-disordered individuals, and
      suggestions are made for the treatment of such cases. Implications for future
      research are also discussed.

PMID- 15488444
TI  - Predictors of body image dissatisfaction and disturbed eating attitudes and
      behaviors in African American and Hispanic girls.
AB  - Disturbed eating attitudes and behaviors are widespread among girls in the United
      States. Because obesity is one of the leading risk factors for eating disorder
      development, African American and Hispanic girls may be at heightened risk due to
      their greater prevalence and degree of overweight. The present study examined the
      associations among disturbed eating attitudes and behaviors, body image
      dissatisfaction, weight classification, fears of negative evaluation, and coping
      skills among 139 African American and Hispanic girls in Grades 4 and 5 from a low
      income urban area. African American girls had significantly lower body image
      dissatisfaction than Hispanic girls. Significant predictors of body image
      dissatisfaction included fear of negative evaluation and weight classification.
      Fear of negative evaluation was also a significant predictor of disturbed eating
      attitudes and behaviors. Overall, 10.1% of the African American girls and 12.7%
      of the Hispanic girls qualified for a diagnosis of a probable eating disorder.
      Girls with eating disorders had greater fears of negative evaluation and engaged
      in more cognitive avoidance. Both groups are at risk of eating disorder
      development.

PMID- 15488445
TI  - A preliminary analysis of binge episodes: comparison of a treatment-seeking
      sample of Black and White women.
AB  - OBJECTIVE: This study sought to examine differences in the nutritional
      composition of binges, both qualitatively and quantitatively, between
      participants with binge eating disorder (BED) and bulimia nervosa (BN) taken from
      a sample of treatment-seeking Black and White women. Overall qualitative and
      quantitative differences between diagnostic categories, regardless of ethnicity,
      were also explored. METHOD: Patients seeking treatment for eating disorders were
      assessed on binge content. Black (n=26) and White (n=26) participants were
      matched on age and body mass index (BMI). RESULTS: The binges of individuals with
      BN were lower in percent protein, but higher in calories, carbohydrates, and
      sugar, than those individuals with BED. However, there was little difference as a
      function of ethnicity between treatment-seeking Black and White women.
      DISCUSSION: Preliminary data suggest that health professionals are faced with
      similar binge eating pathology, regardless of ethnicity, despite, probably,
      etiologic variation. The importance of the role of ethnicity in the expression of
      eating disorders is discussed.

PMID- 15488446
TI  - Cognitive load, stress, and disinhibited eating.
AB  - The impact of cognitive distraction on eating behaviour was examined in
      restrained and unrestrained eaters. It was predicted that restrained eaters would
      eat more than unrestrained eaters following high cognitive load when it involves
      processing of ego-threat information independent of self-reported anxiety. There
      were 119 female participants randomly allocated to one of four experimental
      conditions whereby cognitive load and ego threat were manipulated using modified
      colour-naming Stroop (CNS) tasks. Anxiety ratings were made prior to and
      following experimental tasks. After performing Stroop tasks, participants
      consumed snack foods ad libitum. Restrained eaters consumed significantly more
      food when high cognitive load was ego threatening than when it involved
      processing and memorisation of colour nouns and consumed significantly more than
      unrestrained eaters in a high cognitive load ego-threat condition. Posttask
      anxiety was greater than baseline across all conditions. Task difficulty was
      greater under high cognitive load than low cognitive load as indicated by Stroop
      response times. These results indicated that the escape theory of disinhibited
      eating is conceptually subsumed by a more generalisable limited cognitive
      capacity model.

PMID- 15488447
TI  - High prevalence of abnormal eating and weight control practices among U.S. high
      school students.
AB  - OBJECTIVE: This study sought to determine the prevalence and to identify
      correlates of abnormal eating and weight control practices in U.S. high-school
      students. METHOD: A three-stage cluster design technique was used to select
      15,349 students from 144 different high schools. Each completed the 1999 Youth
      Risk Behavior Survey (YRBS) Questionnaire. RESULTS: Abnormal eating and weight
      control practices during the past month were reported by over 26% of female
      students and 10% of male students. Rates of abnormal eating and weight control
      practices varied by ethnicity and geographic location. Other correlates of
      abnormal eating and weight control practices included having an underweight body
      mass index (BMI): (OR=1.39, 95% CI=1.01-1.91), exercising to control weight in
      past 30 days (OR=1.51, 95% CI=1.30-1.76), dieting to control weight in past 30
      days (OR=3.89, 95% CI=2.65-5.73), and interactions between gender and both weight
      perception and weight satisfaction. DISCUSSION: The high proportion of U.S. high
      school students who have participated in abnormal eating and weight control
      practices in the past month demands immediate attention. The identified
      correlates may help target prevention and control programs.

PMID- 15488448
TI  - Relations among exercise, coping, disordered eating, and psychological health
      among college students.
AB  - Researchers have long been interested in the coping styles of individuals who
      display disordered eating characteristics. Recently, exercise has been recognized
      as both a behavior and coping strategy that might be present among individuals
      with disordered eating. The present study evaluates the role of exercise as both
      a coping mechanism and as a health behavior in relation to eating pathology and
      other measures of psychological health in a nonclinical university population.
      Female (n=235) and male (n=86) undergraduate students completed questionnaires
      that assessed exercise behavior, coping strategies, eating attitudes, self
      esteem, life satisfaction, affect, depression, and anxiety. The results indicate
      that the relations among exercise, coping, and eating pathology is complex.
      Exercise was related to positive psychological health in males, whereas exercise
      in females was associated with both positive and negative psychological health.
      For women with high Eating Attitudes Test (EAT-26) scores, exercise was
      significantly associated with negative affect, and a trend existed in this group
      such that exercise was associated with higher levels of depression and anxiety.
      Conversely, for women with low EAT scores, exercise was associated with positive
      affect. This suggests that exercise might be differentially associated with
      mental health based on the presence or absence of eating pathology.

PMID- 15488449
TI  - Effects of disordered eating and obesity on weight, craving, and food intake
      during ad libitum smoking and abstinence.
AB  - Although there is empirical support for the association between smoking,
      disordered eating, and subsequent weight gain upon smoking cessation, there have
      been no prospective studies to track changes in eating patterns during smoking
      abstinence and explore underlying biobehavioral processes. To help fill these
      gaps, we recruited four groups of women (N=48, 12/group) based on presence vs.
      absence of obesity and on low vs. high risk of severe dieting and/or binge-eating
      to participate in a laboratory study of eating in the context of ad libitum
      smoking and smoking abstinence. Participants [mean age 31.3 years; Fagerstrom
      Test of Nicotine Dependence (FTND) 4.3; smoking rate 18.7 cigarettes/day]
      completed two sessions: one after ad libitum smoking, the other after 2 days'
      smoking abstinence, in counterbalanced order. After a half-day's restricted
      eating, participants watched a video, with measured amounts of preselected
      preferred food available throughout. Cigarettes were available during the ad
      libitum smoking session. High-risk women weighed more after 2 days' abstinence
      than during the ad libitum smoking condition, whereas low-risk women did not
      differ across conditions. Nicotine craving changed significantly more in
      anticipation of nicotine deprivation for high-BMI women than their low-BMI
      counterparts. Caloric intake was marginally attenuated during abstinence for low
      BMI compared with high-BMI participants (P<.10), an effect primarily accounted
      for by differences in protein intake (P<.10). These findings suggest that low-BMI
      women may be less prone to weight gain during early abstinence, possibly because
      they compensate for metabolic changes induced by nicotine washout by eating less.
      Craving increases experienced by high-BMI women during abstinence under
      conditions of food deprivation may contribute to difficulty quitting in these
      women.

PMID- 15488450
TI  - Automatic and nonautomatic processes in dietary restraint: further evidence for a
      commonality between food and drug abstinence.
AB  - The deleterious effect of dietary restraint on cognitive performance is now well
      established. However, recent evidence suggests that this impairment shares
      characteristics with those found in abstinent drug users. In this study, high
      (n=21) and low-to-medium restrained eaters (n=41) completed a reaction-time task,
      once while imagining their favourite food and once while imagining their
      favourite holiday. Afterwards, these participants ate lunch and then completed a
      second set of reaction-time measures. Both before and after lunch, ratings of the
      vividness of the scenarios were similar across groups. Likewise, the groups
      produced similar ratings of hunger, thirst, and desire to eat. However, as
      predicted, performance was significantly impaired in restrained eaters, but only
      while imagining food, and only before lunch. No impairments were observed in the
      low-to-medium restrained group. This finding provides further evidence that
      Tiffany's [Psychol. Rev. 97 (1990) 147] model of drug-related urges can be
      generalised to dietary restraint. The merits of conceptualising dietary restraint
      in terms of automatic and nonautomatic processes are discussed, together with
      suggestions for future research.

PMID- 15488451
TI  - Use of the weight efficacy lifestyle questionnaire with African American women:
      validation and extension of previous findings.
AB  - While the Weight Efficacy Lifestyle Questionnaire (WEL) shows promise as a
      measure of self-efficacy for eating control, there is a lack of research
      examining the psychometric properties of this measure with ethnic minorities. The
      current study examined the WEL with a sample of 144 overweight and obese African
      American females. Analyses indicated similar self-efficacy levels compared to
      predominantly Caucasian samples. Supporting the validity of the WEL, participants
      undergoing obesity treatment demonstrated modest improvement in WEL scores, while
      standard care participants showed no changes in self-efficacy over time. Factor
      analysis indicated a four-factor structure rather than the five factors
      previously found. The four-factor structure accounted for 61.85% of the variance.
      Results indicate the WEL may be a valid measure of self-efficacy for overweight
      and obese African American women, although researchers should be mindful of the
      variation in scale properties when using the WEL with this population.

PMID- 15488452
TI  - NIH in the spotlight over conflicts of interest.

PMID- 15488453
TI  - Lack of evidence for use of glatiramer acetate in multiple sclerosis.

PMID- 15488454
TI  - The results of MATCH: light or heat?

PMID- 15488455
TI  - Mild cognitive impairment: a treatment at last?

PMID- 15488456
TI  - Campylobacter jejuni in Guillain-Barre syndrome.

PMID- 15488457
TI  - Functional neuroimaging of headaches.
AB  - Functional neuroimaging, mainly PET and functional MRI, is the main tool that
      allows the capturing of neurovascular events during a headache attack. In
      migraine, functional imaging has clarified the underlying pathophysiology of the
      visual aura, whereas in migraine without aura, brainstem findings suggest a
      dysfunctional pain system. In cluster headache, the activation and morphological
      changes seen in a region posterior and inferior to the hypothalamus has provided
      a useful therapeutic target using deep-brain stimulation. We will discuss the
      main neuroimaging findings pertaining to the pathophysiology of these two common
      headache disorders, migraine and cluster headache.

PMID- 15488458
TI  - PINK, PANK, or PARK? A clinicians' guide to familial parkinsonism.
AB  - We provide a pragmatic guide for clinicians, and detail the recent developments
      in the genetics of Parkinson's disease that have shaped our current understanding
      and management of this disease and other parkinsonian disorders. These
      developments have been rapid, and in total over 20 genes have been identified,
      three of which were discovered in the past year. Although there are undoubtedly
      more genes to be found, the major challenge for the future is to determine how
      they function and whether they interact. These genes help us to understand the
      heterogeneity of parkinsonism, and also inform on the molecular and clinical
      features of individual parkinsonisms. However, their discovery also requires us
      to raise issues about genetic testing and genetic counselling.

PMID- 15488459
TI  - Chronic epilepsy and cognition.
AB  - Cognitive profiles in epilepsy are as heterogenous as the epileptic syndromes
      themselves; causes, topography of epileptogenic areas, pathogenetic mechanisms,
      and the diverse features characterising the clinical course all contribute to the
      effect on cognition. Chronic epilepsy generally impairs cognition, but it also
      induces processes of functional reorganisation and behavioural compensation. In
      most idiopathic epilepsies, cognition is only mildly deteriorated or even normal
      by clinical standards. Localisation-related cryptogenic and symptomatic epilepsy
      disorders are accompanied by focal deficits that mirror the specific functions of
      the respective areas. Poor cognitive outcome is generally associated with an
      early onset and a long duration of the disease and with poor seizure control.
      There is evidence that cognitive functions are already impaired at the onset of
      the disease, and that the maturation of cognitive functions in children is
      susceptible to the adverse influence of epilepsy. In adults, cognitive decline
      progresses very slowly over decades with an age regression similar to that of
      people without epilepsy. Successful epilepsy surgery can stop or partly reverse
      the unfavourable cognitive development, but left-temporal resections in
      particular have a high risk of additional postoperative verbal memory impairment.
      Cognitive recovery in the adult brain after successful surgery indicates
      functional compensation and, to some degree, functional reorganisation or a
      reactivation of functions previously suppressed by influence from distant but
      connected epileptogenic areas.

PMID- 15488460
TI  - Epidemiology of primary dystonia.
AB  - The prevalence estimates for primary dystonia range from two to 50 cases per
      million for early-onset dystonia and from 30 to 7320 cases per million for late
      onset dystonia. From analysis of methodological information from 14 selected
      studies, we concluded that all studies on the basis of treatment settings or
      record-linkage systems, and two population-based surveys were probably flawed by
      incomplete ascertainment; the third population-based study provided the largest
      prevalence for late-onset dystonia but probably overestimated the prevalence of
      the disorder. Age and ethnic differences among study populations further biased
      comparisons of estimates. On the basis of methodologically more robust service
      based studies and the likely percentage of underdiagnosis in a given area, more
      accurate prevalence estimates may be 111 per million for early-onset dystonia in
      Ashkenazi Jews from New York area, 600 per million for late-onset dystonia in
      northern England, and 3000 per million for late-onset dystonia in the Italian
      population over age 50 years.

PMID- 15488461
TI  - Overt versus covert treatment for pain, anxiety, and Parkinson's disease.
AB  - The recent introduction of covert administration of treatment to biomedical
      research has produced some interesting results, with many clinical and ethical
      implications. Concealed treatment has been used in people with nervous system
      conditions including pain, anxiety, and Parkinson's disease. The main finding is
      that when the patient is completely unaware that a treatment is being given, the
      treatment is less effective than when it is given overtly in accordance with
      routine medical practice. The difference between open and hidden administrations
      is thought to represent the placebo component of the treatment, even though no
      placebo has been given. The decreased effectiveness of hidden treatments
      indicates that knowledge about a treatment affects outcome and highlights the
      importance of the patient-provider interaction. In addition, by use of covert
      administration, the efficacy of some treatments can be assessed without the use
      of a placebo and associated ethical issues.

PMID- 15488462
TI  - The Human Tissue Bill.

PMID- 15488463
TI  - Feather brained.

PMID- 15488464
TI  - Ebselen augments its peroxidase activity by inducing nrf-2-dependent
      transcription.
AB  - Ebselen is an organoselenium compound that acts as a glutathione peroxidase
      mimic. Since ebselen is a hydrophobic, thio-reactive compound capable of
      interacting with Keap-1, we tested its ability to activate nrf-2-dependent
      responses in the human hepatocarcinoma derived cell line, HepG2. Ebselen (25
      microM) increased expression of an nrf-2 response element reporter in transient
      transfection experiments by 4-fold. Although, the induction was lower than that
      observed with classic nrf-2 inducer, sulforaphane (10 microL; 7-fold), ebselen
      also induced expression of native NAD(P)H:quinone oxidoreductase (1.6-fold)
      activity; induction of this protein is known to be dependent on nrf-2 action.
      Treatment of HepG2 cells with ebselen increased glutathione levels after 12 (1.5
      fold) or 24 (1.9-fold)h of treatment. Treatment of the cells with either
      sulforaphane or ebselen 24 h prior to treatment with varying concentrations of t
      butyl hydroperoxide increased the half maximal lethal dose from 28 to 42 microM
      and 58 microM for sulforaphane and ebselen, respectively. The protective effects
      of ebselen treatment were greater with pretreatment (IC50=58 microM) than
      simultaneous addition (IC50=45 microM). The protein synthesis inhibitor
      cycloheximide blocked increases in intracellular glutathione synthesis and
      partially blocked the protective effects of this regimen on increasing cell
      survival following t-butyl hydroperoxide treatment. Likewise co-treatment with
      the MEK 1 inhibitor, PD98059, which has been shown to inhibit nrf-2-dependent
      gene activation, partially inhibited the ebselen-dependent increases in IC50
      while not affecting the control cells. We conclude that nrf-2 activation augments
      the role of ebselen as an antioxidant or by indirect induction of cellular
      antioxidant defences.

PMID- 15488465
TI  - Characterization of soluble and putative membrane-bound UDP-glucuronic acid
      decarboxylase (OsUXS) isoforms in rice.
AB  - Arabinoxylans in crop plants are the major sugar components of the cell walls,
      and UDP-xylose is a key substrate in the biosynthesis of xylans. In this study,
      the six putative UDP-D-glucuronic acid decarboxylase genes from rice (Oryza
      sativa UDP-xylose synthase; OsUXS) were cloned. Except for the soluble form of
      OsUXS3 (GenBank Accession No. ?AB079064), the remaining five OsUXS enzymes
      contain a putative membrane-bound region. The six OsUXS genes were classified
      into three types by phylogenetic analysis and were expressed during the
      development of rice seeds. The HPLC retention times of the enzyme products and
      NMR data, indicate that the recombinant OsUXS2 enzyme catalyzes the conversion of
      UDP-D-glucuronic acid to UDP-D-xylose. Interestingly, the reactions catalyzed by
      the recombinant OsUXS2 and OsUXS3 enzymes were inhibited by NADP+, and
      accelerated by NADPH. The catalytic activities of the recombinant OsUXS2 and
      OsUXS3 enzymes were strongly inhibited by UDP, UTP, TDP, and TTP. The expression
      levels of OsUXS genes changed in different manners during the development of rice
      seeds, suggesting that each corresponding OsUXS enzyme plays a significant role
      in rice seed development at a certain stage. In the present study, we report that
      the UXS2-type enzyme of rice is not only characterized for the first time but
      also show significant findings involved in the gene expression of OsUXSs.

PMID- 15488466
TI  - Oxidation of cysteine and homocysteine by bovine albumin.
AB  - The autooxidation of cysteine and homocysteine to their disulfide forms was
      determined by measuring the time course of thiol groups disappearance. We found
      the oxidative chemistry of cysteine and homocysteine to be quite different. In
      the absence of added Cu(II), cysteine autooxidized at a slower rate than
      homocysteine, though in its presence cysteine oxidation was much faster,
      homocysteine being found to be a poor responder to copper catalysis. Albumin
      speeded up the spontaneous oxidation of both aminothiols, the reaction being
      faster with cysteine than with homocysteine. The copper content of different
      albumins was found to be highly variable, ranging from 12.75 to 0.64 microg
      Cu(II)/g albumin. We propose that copper bound to albumin possesses redox cycling
      activity to perform cysteine oxidation since: (i) copper elimination by copper
      chelators markedly reduces oxidation; and (ii) a positive correlation exists
      between the albumin copper content and the oxidation reaction rate.

PMID- 15488467
TI  - Cobalamin (vitamin B12) binding, phylogeny, and synteny of human transcobalamin.
AB  - Selected residues in a highly conserved 15-residue region, 174SVDTAAMAGLAFTC L188
      of human transcobalamin (TC), a cobalamin (Cbl: vitamin B12) binding protein,
      were subjected to site-directed mutagenesis. The mutant constructs were expressed
      in TC-deficient fibroblasts or in vitro to assess the effect of these mutations
      on Cbl binding. Phylogenetic analyses and protein parsimony indicated that TC
      evolved earlier than other mammalian Cbl-binding proteins, intrinsic factor and
      haptocorrins, and divergence occurred between mouse/rat and human dispersing TC
      gene to different chromosomes. These studies show that (a) two of the three polar
      residues, S174, T177, or D176 and two of the three conserved alanine residues,
      A179 and A184 present in the 15-residue evolutionary conserved region are
      essential for Cbl-binding by human TC, and (b) TC gene is transferred in a
      syntenic manner to different chromosomes, at least before the divergence of
      mouse/rat and human.

PMID- 15488468
TI  - Purification and characterization of a stimulator of plasmin generation from the
      antiangiogenic agent Neovastat: identification as immunoglobulin kappa light
      chain.
AB  - We have recently shown that Neovastat, an antiangiogenic extract from shark
      cartilage, stimulates the in vitro activation of plasminogen by facilitating the
      tissue-type plasminogen activator (tPA)-dependent conversion of plasminogen to
      plasmin. In this report, we describe the purification and characterization of the
      stimulatory molecules. Neovastat was subjected to a three-step purification
      procedure including gel filtration, preparative isoelectric focusing, and
      preparative SDS-PAGE. Two 28-kDa proteins with pIs of approximately 4.5 and 6.5
      were purified to apparent homogeneity and identified as immunoglobulin (Ig) kappa
      light chains by N-terminal microsequencing. Ig light chains do not directly
      stimulate the activity of tPA or plasmin, suggesting a mechanism of action
      involving an interaction with plasminogen. Kinetic analysis showed that both Ig
      light chains accelerate the in vitro tPA-dependent conversion of plasminogen in
      plasmin by increasing the affinity of tPA for plasminogen by 32- and 38-fold (Km
      decrease from 456 nM to 12-14 nM). Shark Ig light chains also stimulated the
      degradation of fibrin by the tPA/plasminogen system in an in vitro assay. A
      direct interaction between Ig light chains and plasminogen (KA=4.0-5.5 x 10(7) M(
      1); KD=18-25 nM) and with tPA (KA=2.8 x 10(7) M(-1); KD=36 nM) was demonstrated
      using real time binding measured by surface plasmon resonance. Ig light chain is
      the first molecule associated with the antiangiogenic activity of Neovastat to be
      purified and identified.

PMID- 15488469
TI  - Expression of a familial amyotrophic lateral sclerosis-associated mutant human
      superoxide dismutase in yeast leads to decreased mitochondrial electron
      transport.
AB  - Strains of Saccharomyces cerevisiae that express either the wild type or the
      amyotrophic lateral sclerosis-associated mutant human copper-zinc superoxide
      dismutase (SOD1) proteins A4V and G93A, respectively, in a yeast SOD1-deficient
      parent strain were used to investigate the hypothesis that expression of a mutant
      SOD1 protein causes deficient mitochondrial electron transport as a possible
      mechanism for disease induction. Mitochondria isolated from the wild type SOD1
      expressing yeast were identical to mitochondria from the parent strain in heme
      content and activities of complexes II, III, and IV. Mitochondria isolated from
      the A4V-expressing yeast had decreased rates of electron transport in complexes
      II+III, III, and IV and corresponding decreases in hemes b, c-c1, and a-a3
      content compared to mitochondria from wild type human SOD1-expressing yeast.
      Mitochondria isolated from G93A-expressing yeast had decreased rates of electron
      transport in complex IV and probably in complex II with a corresponding decrease
      in heme a-a3 content. These results suggest that mutant SOD1-expression causes
      defective electron transport complex assembly and that the yeast system will
      provide an excellent model for the study of the mechanism of mutant SOD1-induced
      mitochondrial electron transport defects.

PMID- 15488470
TI  - Fluoroalcohol-induced stabilization of the alpha-helical intermediates of lentil
      lectin: implication for non-hierarchical lectin folding.
AB  - An intermediate state of lentil lectin was characterized at pH 1 having low
      content of secondary as well as tertiary structure. Far- and near-UV CD
      spectroscopy showed loss of structure when pH was lowered from 7 to 0.8 but the
      structure loss was less than that of the protein in presence of 6M GndHCl.
      Intrinsic tryptophan fluorescence studies, ANS binding, and acrylamide quenching
      experiments supported the existence of the intermediate at low pH. The unfolding
      process of lentil lectin at pH 1 was also studied by GndHCl denaturation
      monitored by intrinsic fluorescence spectroscopy. The non-cooperative unfolding
      at pH 1, in contrast to cooperative unfolding of the native protein further
      confirmed the presence of loose tertiary structure. The unfolded structure of the
      lectin at pH 1 was also shown by limited tryptic digestion studies. Further
      studies were performed on this intermediate state of lentil lectin obtained at
      low pH in presence of fluoroalcohols 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3
      hexafluoroisopropanol (HFIP). Lentil lectin is mainly a beta-sheet protein, and
      both TFE and HFIP stabilized the acid unfolded structure by inducing alpha
      helical contacts. Interestingly, it was observed that induction of the non-native
      structure resulted in regain of protein activity to some extent. At pH 1, loss in
      activity was found with both dextran and bromelain while the reported
      intermediate at the given pH was found to regain activity with bromelain in
      presence of HFIP and TFE. HFIP induced more structure as compared to TFE and
      hence a greater regain in activity of about 30% was observed with HFIP as
      compared to a 15% regain with TFE. Activity with dextran in presence of
      fluoroalcohols could not be determined as turbidity developed in the
      corresponding blank preparations. Our results presented here point out the
      possibility of the formation of a helical structure preceding the formation of
      the native beta-sheet structure and thus support the non-hierarchical model of
      protein folding for lentil lectin.

PMID- 15488471
TI  - Differential accumulation of Glut1 in the non-DRM domain of the plasma membrane
      in response to the inhibition of oxidative phosphorylation.
AB  - Approximately 50% of Glut1 in the plasma membrane of Clone 9 cells is localized
      to the detergent-resistant membrane (DRM) fraction. Acute exposure (90 min) to
      5mM azide stimulated glucose transport by approximately 4.7-fold and increased
      the abundance of Glut1 in the non-DRM fraction of the plasma membrane by
      approximately 2.9-fold while the abundance of Glut1 in the DRMs was not changed.
      In parallel experiments, approximately 17 h exposure to azide further increased
      the rate of glucose transport over that observed at 90 min by approximately 33%
      and increased plasma membrane Glut1 content by approximately 3.5-fold over
      control. The increase in total plasma membrane Glut1 reflected a approximately
      4.7-fold increase of Glut1 content in the non-DRM fraction and a approximately
      2.6-fold increase in the DRMs. We conclude that acute exposure to azide increases
      Glut1 content in the non-DRM fractions, while prolonged exposure to azide
      increases the Glut1 content in both non-DRM and DRM fractions. These changes may
      play an important role in the stimulation of glucose transport in response to the
      inhibition of oxidative phosphorylation.

PMID- 15488472
TI  - Cytochrome b5 reductase: the roles of the recessive congenital methemoglobinemia
      mutants P144L, L148P, and R159*.
AB  - Recessive congenital methemoglobinemia (RCM, OMIM 250800) arises from defects in
      either the erythrocytic or microsomal forms of the flavoprotein, cytochrome b5
      reductase (cb5r) and was the first disease to be directly associated with a
      specific enzyme deficiency. Of the 33 verified mutations in cb5r that give rise
      to either the type I (erythrocytic) or type II (generalized) forms of RCM, three
      of the mutations, corresponding to P144L, L148P, and R159*, are located in a
      segment of the primary sequence composed of residues G143 to V171 which serves as
      a "hinge" or "linker" region between the FAD- and NADH-binding lobes of the
      protein. With the exception of R159*, which produces a truncated non-functional
      cb5r resulting in type II RCM, the type I methemoglobinemias resulting from the
      P144L or L148P mutations have been proposed to be due to decreased enzyme
      stability. Utilizing a recombinant form of the rat cb5r enzyme, we have generated
      the P144L, L148P, and P144L/L148P mutants, purified the resulting proteins to
      homogeneity and characterized their spectroscopic, kinetic, and thermodynamic
      properties. The three mutant proteins retained full complements of FAD with the
      P144L and L148P variants being spectroscopically indistinguishable from wild-type
      cb5r. In contrast, kinetic analyses revealed that the P144L, L148P, and
      P144L/L148P variants retained only 28, 31, and 8% of wild-type NADH:cytochrome b5
      reductase activity, respectively, together with significant alterations in
      affinity for both NADH and NAD+. In addition, FAD oxidation-reduction potentials
      were 32, 19, and 65 mV more positive for the mutants than the corresponding
      FAD/FADH2 couple in native cb5r (E0'=-272 mV). Thermal and proteolytic stability
      measurements indicated that all three mutants were less stable than the wild-type
      protein while differential spectroscopy indicated altered pyridine nucleotide
      binding in all three variants. These results demonstrate that the "hinge" region
      is important in maintaining the correct orientation of the flavin- and pyridine
      nucleotide-binding lobes within the protein for efficient electron transfer and
      that the P144L and L148P mutations disrupt the normal registration of the FAD-
      and NADH-binding lobes resulting in altered affinities for both the physiological
      reducing substrate, NADH and its product, NAD+.

PMID- 15488473
TI  - Functional effect of hydrogen peroxide on the sarcoplasmic reticulum membrane:
      uncoupling and irreversible inhibition of the Ca2+-ATPase protein.
AB  - The chemical treatment of sarcoplasmic reticulum vesicles with H2O2 affects both
      Ca2+ transport and the hydrolytic activity supported by the Ca2+-ATPase protein.
      Ca2+ transport was much more sensitive to inhibition than ATPase activity and the
      decrease in Ca2+ transport was not the result of an increase in membrane
      permeability. The Ca2+/Pi uncoupling can be attributed to the own catalytic
      mechanism of the enzyme. Under conditions of high uncoupling, Ca2+ binding to the
      transport sites was barely affected and accumulation of phosphorylated species
      during the enzyme cycling gave almost maximal levels. These are features defining
      intramolecular uncoupling mediated by a phosphorylated form of the enzyme. Severe
      inhibition of the hydrolytic activity was observed when higher peroxide
      concentrations and leaky vesicles were used. These experimental conditions
      diminished maximal Ca2+ binding and the steady-state phosphoenzyme level. The low
      hydrolytic activity can be ascribed to a decrease in the rate of enzyme
      dephosphorylation.

PMID- 15488474
TI  - The pig CYP2E1 promoter is activated by COUP-TF1 and HNF-1 and is inhibited by
      androstenone.
AB  - Functional analysis of the pig cytochrome P4502E1 (CYP2E1) promoter identified
      two major activating elements. One corresponded to the hepatic nuclear factor 1
      (HNF-1) consensus binding sequence at nucleotides -128/-98 and the other was
      located in the region -292/-266. The binding of proteins in pig liver nuclear
      extracts to a synthetic double-stranded oligonucleotide corresponding to this
      more distal activating sequence was studied by electrophoretic mobility shift
      assay. The minimum protein binding sequence was identified as TGTTCTGACCTCTGGG.
      Gel super-shift assays identified the protein binding to this site as chick
      ovalbumin upstream promoter transcription factor 1 (COUP-TF1). Androstenone
      inhibited promoter activity in transfection experiments only with constructs
      which included the COUP-TF1 binding site. Androstenone inhibited COUP-TF1 binding
      to synthetic oligonucleotides but did not affect HNF-1 binding. The results offer
      an explanation for the inhibition of CYP2E1 protein expression by androstenone in
      isolated pig hepatocytes and may be relevant to the low expression of hepatic
      CYP2E1 in those pigs which accumulate high levels of androstenone in vivo.

PMID- 15488475
TI  - C-25 hydroxylation of 1alpha,24(R)-dihydroxyvitamin D3 is catalyzed by 25
      hydroxyvitamin D3-24-hydroxylase (CYP24A1): metabolism studies with human
      keratinocytes and rat recombinant CYP24A1.
AB  - Recently, 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) has been shown to
      catalyze not only hydroxylation at C-24 but also hydroxylations at C-23 and C-26
      of the secosteroid hormone 1alpha, 25-dihydroxyvitamin D3 (1alpha,25(OH)2D3). It
      remains to be determined whether CYP24A1 has the ability to hydroxylate vitamin
      D3 compounds at C-25. 1alpha,24(R)-dihydroxyvitamin D3 (1alpha,24(R)(OH)2D3) is a
      non-25-hydroxylated synthetic vitamin D3 analog that is presently being used as
      an antipsoriatic drug. In the present study, we investigated the metabolism of
      1alpha,24(R)(OH)2D3 in human keratinocytes in order to examine the ability of
      CYP24A1 to hydroxylate 1alpha,24(R)(OH)2D3 at C-25. The results indicated that
      keratinocytes metabolize 1alpha,24(R)(OH)2D3 into several previously known both
      25-hydroxylated and non-25-hydroxylated metabolites along with two new
      metabolites, namely 1alpha,23,24(OH)3D3 and 1alpha,24(OH)2-23-oxo-D3. Production
      of the metabolites including the 25-hydroxylated ones was detectable only when
      CYP24A1 activity was induced in keratinocytes 1alpha,25(OH)2D3. This finding
      provided indirect evidence to indicate that CYP24A1 catalyzes C-25 hydroxylation
      of 1alpha,24(R)(OH)2D3. The final proof for this finding was obtained through our
      metabolism studies using highly purified recombinant rat CYP24A1 in a
      reconstituted system. Incubation of this system with 1alpha,24(R)(OH)2D3 resulted
      in the production of both 25-hydroxylated and non-25-hydroxylated metabolites.
      Thus, in our present study, we identified CYP24A1 as the main enzyme responsible
      for the metabolism of 1alpha,24(R)(OH)2D3 in human keratinocytes, and provided
      unequivocal evidence to indicate that the multicatalytic enzyme CYP24A1 has the
      ability to hydroxylate 1alpha,24(R)(OH)2D3 at C-25.

PMID- 15488476
TI  - Increased formation of short-chain organic acids after chronic ethanol
      administration and its interaction with the carnitine pool in rat.
AB  - Organic acidurias are genetic disorders of mitochondrial metabolism that lead to
      the accumulation of organic acids in tissues and biological fluids. It has been
      demonstrated that interaction of carnitine with the cellular coenzyme A (CoA)
      pool, through the production of acyl-carnitines, is potentially critical for
      maintaining normal cellular metabolism under condition of impaired acyl-CoA use
      and that exposure of humans and other mammals to ethanol leads to impairment of
      mitochondrial function. The aim of the present study was to evaluate the role of
      chronic administration of ethanol on urinary excretion of short-chain organic
      acids and endogenous carnitines in rats. The data reported show that chronic
      administration of ethanol significantly increases urinary excretion of
      propionate, methylmalonate, as well as free acetate, butyrate, pyruvate, lactate,
      and beta-hydroxybutyrate. Chronic administration of propranolol abolished ethanol
      dependent accumulation of propionate, suggesting involvement of beta-adrenergic
      mechanisms. Increased formation of propionate and methylmalonate was associated
      with decreased plasma carnitine levels and with increased excretion of specific
      acyl-carnitines, corresponding to the accumulating acyl groups. Our data indicate
      that chronic alcohol ingestion induces increased excretion of selected organic
      acids and that the endogenous carnitine pool might exert a protective role
      against the deleterious effects of accumulating short-chain organic acids.

PMID- 15488477
TI  - Chronic antidepressant medication attenuates dexamethasone-induced neuronal death
      and sublethal neuronal damage in the hippocampus and striatum.
AB  - Dexamethasone, a synthetic corticosteroid, which can induce a range of mood
      disorders including depression and affective psychosis, is toxic to specific
      hippocampal and striatal neuronal populations. Chronic administration of
      antidepressants can induce neuroprotective effects, potentially by raising
      cellular levels of brain-derived neurotrophic factor (BDNF). We accordingly
      tested the hypothesis that chronic pretreatment of rats (Sprague-Dawley, male)
      with antidepressants would attenuate dexamethasone-induced neuronal damage as
      revealed by reductions in the level of neuronal death and in sublethal neuronal
      damage shown by the increase in the number of MAP-2 immunoreactive neurons. In
      support of this hypothesis, we demonstrate that chronic treatment with a range of
      antidepressants prior to dexamethasone administration (0.7 mg/kg, i.p.)
      attenuated the levels of neuronal death and loss of MAP-2 immunoreactivity in
      both the hippocampus and striatum. The antidepressants used were: desipramine (8
      mg/kg, i.p., tricyclic), fluoxetine (8 mg/kg, i.p., selective serotonin reuptake
      inhibitor) and tranylcypromine (10 mg/kg, i.p., monoamine oxidase inhibitor) with
      each drug being injected once per day for 10 days. In contrast, acute injection
      of none of the antidepressants exerted a protective effect from dexamethasone
      associated neuronal damage. Similarly, injection of neither cocaine nor
      chlordiazepoxide (benzodiazepine) exerted protective effects when injected either
      chronically or acutely. The observed protection from dexamethasone-induced
      neuronal damage is in keeping with the potential of chronic antidepressant
      medication to increase BDNF levels. The potential for dexamethasone to induce
      disorders of mood by damaging specific neuronal populations in the hippocampus
      and dorsomedial striatum is discussed.

PMID- 15488478
TI  - Potassium channel subunit Kv3.2 and the water channel aquaporin-4 are selectively
      localized to cerebellar pinceau.
AB  - The pinceau is a cerebellar structure formed by descending GABA-ergic basket cell
      axonal terminals converging on the initial axonal segment of Purkinje cell.
      Although basket cells exert a powerful inhibitory influence on the output of the
      cerebellar cortex, the function and mode of action of the pinceau are not
      understood because the majority of basket cell axons fail to make identifiable
      synaptic contacts with the Purkinje cell axon. Several proteins were previously
      reported to cluster specifically in this area, including a number of voltage
      activated potassium channel subunits. In this study, we used
      immunohistochemistry, electron microscopy, and electron tomography to examine the
      ultrastructural localization of a novel voltage-gated potassium channel subunit,
      Kv3.2, in the pinceau. We found strong, selective localization of Kv3.2 to basket
      cell axons. Additionally, because potassium buffering is often conducted through
      water channels, we studied the extent of a brain-specific water channel,
      aquaporin-4 (AQP4), using confocal and electron microscopy. As expected, we found
      AQP4 was heavily localized to astrocytic processes of the pinceau. The abundance
      of potassium channels and AQP4 in this area suggests rapid ionic dynamics in the
      pinceau, and the unusual, highly specialized morphology of this region implies
      that the structural features may combine with the molecular composition to
      regulate the microenvironment of the initial segment of the Purkinje cell axon.

PMID- 15488479
TI  - Sensory stimulation accelerates dopamine release in the basal ganglia.
AB  - We report herein the modulation of dopamine release in the basal ganglia during
      peripheral electrical stimulation in animals. The endogenous dopamine release
      during electrical stimulation was measured in anesthetized cats by positron
      emission tomography (PET) using the D2 receptor agonist [11C]-raclopride. Binding
      potential (BP) parametric maps were calculated using a simplified reference
      region model. The regional dopamine release evoked by electrical stimulation was
      estimated both by region of interest (ROI) analysis and statistical parametric
      mapping (SPM 99). Both ROI analysis and statistical parametric mapping showed
      significant release of endogenous dopamine in the nucleus accumbens and the
      striatum contralateral to the stimulated side as compared to the resting
      condition as well as the ipsilateral side. Accordingly, we suggest that the
      activity of the dopaminergic neurons in the midbrain projecting to the nucleus
      accumbens and the striatum is modulated by the input from the afferent nerves.
      This provides an in vivo evidence for the importance of the basal ganglia in the
      processing of peripheral information required for normal movement. This may also
      explain the clinically observed sensory system abnormalities in patients with
      movement disorders.

PMID- 15488480
TI  - Sialic acid contributes to hyperexcitability of dorsal root ganglion neurons in
      rats with peripheral nerve injury.
AB  - Axonal injury of the dorsal root ganglion (DRG) neurons may alter the synthesis
      of certain membrane proteins that are responsible for the development of abnormal
      hyperexcitability. The external domains of most of these membrane proteins are
      sialylated. Because sialic acid carries heavy negative charges, the increase of
      sialylated proteins may increase neurons' negative surface charges, which will
      have predictable effects on the voltage-gated channels, and affect the
      excitability of injured neurons. Using intracellular electrophysiological
      recording, we demonstrated that following chronic constriction injury (CCI) of
      the sciatic nerve, Aalpha/beta DRG neurons become hyperexcitable, as indicated by
      a more depolarized resting membrane potential (Vm) and a lowered threshold
      current (TIC). More interestingly, the excitability of injured DRG neurons was
      reduced substantially when the extracellular sialic acid was removed by
      pretreatment with neuraminidase. The Vm was less depolarized and the TIC
      increased robustly as compared to the CCI neurons without neuraminidase
      treatment. However, desialylation of normal, intact neurons had no significant
      effect on the Vm and less effect on the TIC. Our results suggest that the
      hyperexcitability of injured sensory neurons may be associated with increased
      negatively charged sialic acid residues on the surface of the neuronal somata.

PMID- 15488481
TI  - Differential effects of ischemia/reperfusion on amacrine cell subtype-specific
      transcript levels in the rat retina.
AB  - Transient retinal ischemia induces loss of retinal ganglion cells, supporting the
      hypothesis that ischemic conditions contribute to the induction and progression
      of glaucoma. However, after 60 min of ischemia, also amacrine cells are lost from
      the inner nuclear layer. The main goal was to determine the relative
      vulnerability of various amacrine subpopulations by measuring the levels of
      transcripts that are known to be specifically expressed by different amacrine
      subpopulations. A 60-min ischemic period was administered to the rat eye by
      raising the intraocular pressure, followed by a reperfusion period lasting
      between 2 h and 4 weeks. Total RNA was isolated from the whole retina and
      expression levels were assessed by real-time quantitative polymerase chain
      reaction (qPCR). Retinal ischemia/reperfusion has differential effects on the
      levels of the various transcripts. Three main patterns of changes were
      identified. (i) A gradual decrease of transcript level without recovery was
      observed for parvalbumin; this transcript is expressed by the glycinergic AII
      cells. (ii) A gradual reduction to different levels at 72 h of reperfusion
      followed by a partial or complete recovery (glycine transporter 1, glutamate
      decarboxylase, calretinin, and several other transcripts). The glycinergic
      amacrine cell markers recovered to 65-75% of the control level, while the main
      GABAergic markers had completely recovered at 4 weeks. (iii) No significant
      changes of transcript levels were found for markers of several smaller GABAergic
      subpopulations [including substance P (Tac1), somatostatin, and others].
      Expression levels of photoreceptor-, horizontal cell-, and bipolar cell-specific
      transcripts were not altered. These patterns were confirmed by a cluster analysis
      of the data. Based on gene expression levels, it may be concluded that amacrine
      cells are vulnerable to ischemic insults and that the glycinergic amacrine cells
      are relatively more sensitive to ischemia than the GABAergic population. In
      particular, the extensive loss of the parvalbumin-containing AII amacrine cells,
      which serve in the rod pathway, may have functional implications for vision under
      scotopic conditions. In the accompanying paper [F. Dijk and W. Kamphuis, An
      immunocytochemical study on specific amacrine subpopulations in the rat retina
      after ischemia, Brain Res. (2004).], the results are evaluated at the protein
      level by immunostaining for a selection of the amacrine cell markers.

PMID- 15488482
TI  - An immunocytochemical study on specific amacrine cell subpopulations in the rat
      retina after ischemia.
AB  - Transient retinal ischemia leads to the loss of neurons in the inner retina. In
      an accompanying paper [F. Dijk, S. Van Leeuwen, W. Kamphuis, Differential effects
      of ischemia/reperfusion on amacrine cell subtype-specific transcript levels in
      the rat retina, Brain Res., 1026 (2004) 194-204] we present the results of a
      study on the effects of experimentally induced retinal ischemia on transcript
      levels of genes expressed by distinct subpopulations of amacrine cells. In
      response to 60-min ischemia, three different patterns of changes in transcript
      levels were found, indicating a differential vulnerability of amacrine subtypes:
      (i) a gradual decrease of transcript level without recovery (parvalbumin; PV);
      (ii) a gradual decrease, with varying rates and degrees, followed by partial
      recovery after 72 h of reperfusion (choline acetyltransferase (ChAT), calretinin
      (CR) and glycine transporter (Glyt1)); (iii) no significant changes (substance P
      (SP)). In order to verify whether the degree of cell loss can be predicted from
      the quantified alterations in gene expression level, immunocytochemical stainings
      were carried out. A 60-min ischemic period was administered to the rat eye by
      raising the intraocular pressure, followed by a reperfusion period lasting
      between 2 h and 4 weeks. Cryosections were immunostained for Glyt1, PV, ChAT, CR,
      and SP. Double-labelling with apoptosis marker TUNEL was used to demonstrate cell
      type-specific apoptosis. Following ischemia, the numbers of detected PV-, Glyt1,
      ChAT-, and CR-immunopositive somata showed a substantial, but differential,
      reduction at 1-4 weeks after ischemia. The total amount of immunoreactivity
      present in the inner plexiform layer (IPL) also decreased. The extent of
      alterations derived from immunocytochemical staining was greater than was
      anticipated from the decrease of transcript levels. Only for SP, no significant
      decrease in number of cells or in the intensity of immunoreactivity in IPL was
      observed, which is in agreement with the absence of significant changes in
      transcript levels. In conclusion, retinal ischemia/reperfusion differentially
      affects amacrine cell populations. Although both protein and mRNA levels are
      reduced, transcript levels are less attenuated. Caution must be applied in the
      use of real-time quantitative PCR (qPCR) screening as a tool to assess the
      cellular pattern of neurodegeneration in the retina.

PMID- 15488483
TI  - Acute changes in cortical excitability in the cortex contralateral to focal
      intracerebral hemorrhage in the swine.
AB  - Injury to the cerebral cortex results in functional deficits not only within the
      vicinity of the lesion but also in remote brain regions sharing neuronal
      connections with the injured site. To understand the electrophysiological basis
      of this phenomenon, we evaluated the effects of a focal intracerebral hemorrhage
      (ICH) on cortical excitability in a remote, functionally connected brain region.
      Cortical excitability was assessed by measuring the somatic evoked potential
      (SEP) elicited by electrical stimulation of the swine snout, which is
      somatotopically represented in the rostrum area of the primary somatosensory (SI)
      cortex. The SEP was measured on the SI cortex ipsilateral to the site of ICH and
      on the contralateral SI cortex during the acute period (< or =11 h) after
      collagenase-induced ICH. The ICH rapidly attenuated the SEP on the ipsilateral
      cortex as we reported earlier. Interestingly, the ICH also attenuated the SEP on
      the contralateral SI cortex. Evoked potentials in the contralateral SI cortex
      showed a gradual decrease in amplitude during this acute period of ICH. We then
      investigated whether the interhemispheric connections shared by the contralateral
      SI and the lesion cortex were responsible for the diminished evoked potentials in
      the uninjured hemisphere after ICH. A separate group of animals underwent corpus
      callosal transection prior to electrocorticography (ECoG) recordings and ICH
      injury. Within hours of hemorrhagic injury, a gradual but marked increase in
      evoked potential amplitude was observed in the homotopic SI cortex of
      callosotomized animals as compared to pre-injection recordings. The enhancement
      suggests that there are additional effects of ICH on remote areas functionally
      connected to the site of injury. Functional deficits were present in both SI
      cortices within the first several hours of a unilateral injury indicating that
      the cessation of brain activity in the lesioned SI is mirrored in the
      contralateral hemisphere. This electrophysiological depression in the uninjured
      SI cortex is mediated in part by the interhemispheric connections of the corpus
      callosum.

PMID- 15488484
TI  - Depressed cortical excitability and elevated matrix metalloproteinases in remote
      brain regions following intracerebral hemorrhage.
AB  - The absence of cortical responses to external stimuli is a dubious clinical sign
      during the first 1-2 days of brain injury. We previously showed that the
      amplitude of the somatic evoked potential (SEP) in the swine is diminished at the
      infarct site and perihematomal surround within the first 6 h of collagenase
      induced intracerebral hemorrhage (ICH). We now report that this depressed SEP
      persists during the subchronic (48 h) period of ICH in the swine not only within
      the injured primary somatosensory (SI) cortex, but also in the contralateral
      homotopic SI cortex. This impairment of sensory responsiveness was accompanied by
      increases in various matrix metalloproteinases (MMPs) in different brain regions.
      By 24 h, a marked rise in MMP-9, an inflammatory marker, was detected in the
      white matter of the ipsilesional SI and secondary somatosensory cortex (SII), and
      in the contralesional SI gray matter, as compared to saline-injected controls. A
      subsequent increase in MMP-9 level was found in the ipsilesional SI and SII gray
      matter, and in the contralesional SI white matter by 48 h (P<0.05). By 7 days,
      significant levels of MMP-9 were detected only in the ipsilesional SI white and
      gray matter tissues. In contrast, the elevation of MMP-2, a marker of
      degeneration, was delayed until 7 days post-ICH in the ipsilesional SII gray
      matter. A significant rise in MMP-9 was also noted in CA1 of the ipsilesional and
      contralesional hemispheres during 1-2 days. Our MMP assay shows that the
      depressed cortical excitability seen in the contralateral SI cortex is a
      manifestation of the broad effect of a focal ICH that produces inflammatory and
      degenerative processes not only in the region adjacent to the focal ICH site, but
      also in remote regions that are functionally connected to the site of focal ICH.

PMID- 15488485
TI  - Mitochondrial accumulation in the distal part of the initial segment of chicken
      spinal motoneurons.
AB  - The axonal initial segment is the initiation site of action potentials and is
      characterized morphologically by a dense undercoating and fascicles of
      microtubules connected by cross-bridges. In order to analyze subcellular
      structures in the initial segment, we made serial transverse sections of initial
      segments of identified chicken motoneurons by retrograde transport of horseradish
      peroxidase (HRP) injected into the muscle. The mean (+/-SD) length of the initial
      segment was 28.1+/-2.3 microm (n=6). Mitochondria accumulated in the distal part
      of the initial segment, which was 1.4-6.9 microm in length (5-23% of the total
      length of the initial segment). In the transverse section of the distal part,
      mitochondrial density was 15.8+/-6.2% (n=5), while in the middle and proximal
      parts it was 6.1+/-1.6% and 5.6+/-1.4%, respectively. Mitochondrial accumulation
      was observed in common in phasic and tonic motoneurons in the chicken, and also
      observed in the distal part of the initial segment of the large ventral horn
      neurons of the chicken without HRP injection. These findings suggest that
      accumulated mitochondria play an important role in maintaining the physiological
      function of the distal part of the motoneuron initial segment.

PMID- 15488486
TI  - A cannabinoid receptor antagonist attenuates conditioned place preference but not
      behavioural sensitization to morphine.
AB  - The present study compared the effects of the cannabinoid receptor antagonist SR
      141716 on morphine-induced locomotor sensitization (Experiment 1) and conditioned
      place preference (CPP, Experiment 2) in male albino Wistar rats. In Experiment 1,
      rats received seven consecutive daily treatments with morphine (10 mg/kg, SC) in
      combination with either SR 141716 (0, 0.1, 0.5 or 3.0 mg/kg, IP), or naloxone (10
      mg/kg, IP). Three days later, all rats were challenged with a lower dose of
      morphine (5 mg/kg, SC). Rats pre-treated with morphine showed significantly
      elevated locomotor activity during the challenge session compared to vehicle-pre
      treated animals indicating behavioural sensitization. Prior naloxone, but not SR
      141716, co-administration with morphine, significantly attenuated the locomotor
      sensitization observed. In Experiment 2A, SR 141716 (0.1 mg/kg, IP), co
      administered during conditioning, significantly attenuated the place preference
      produced by morphine (4 mg/kg, SC) in a standard unbiased two compartment place
      conditioning task. In Experiment 2B, the timing of drug administration and drug
      doses used were altered to be similar to Experiment 1, such that a comparison
      between the sensitization and CPP paradigms could be made. Thus, rats were
      conditioned with morphine (10 mg/kg, SC) combined with SR 141716 (0, 0.1, 0.5 or
      3.0 mg/kg, IP) and tested for place preference under the influence of morphine (5
      mg/kg, SC). SR 141716 attenuated morphine place preference at a dose (3.0 mg/kg)
      that did not itself affect place conditioning. Morphine also induced locomotor
      sensitization in the drug-paired compartment in Experiment 2B which was not
      blocked by any dose of SR 141716. We conclude that CB1 receptor antagonism
      modulates the rewarding value of opioids, but not the behavioural sensitization
      induced by chronic opioid administration.

PMID- 15488487
TI  - Estradiol acutely attenuates glutamate-induced calcium overload in primarily
      cultured rat hippocampal neurons through a membrane receptor-dependent mechanism.
AB  - Increasing lines of evidence indicate that estrogen acts as a neuroprotective
      agent through a nongenomic mechanism. We tested the hypothesis that 17beta
      estradiol could rapidly attenuate glutamate-induced calcium (Ca2+) overload in
      rat primary hippocampal neurons via a membrane receptor-dependent mechanism. The
      bulk cytosolic intracellular Ca2+ level was measured in neurons with fluorescent
      Ca2+ probe fluo3. Preexposure of primary cultured hippocampal neurons to 17beta
      estradiol for 3 min attenuated intracellular Ca2+ increase induced by glutamate
      in a concentration-dependent manner. The action of 17beta-estradiol was
      reversible after washout. Administration of membrane-impermeable 17beta-estradiol
      conjugated to bovine serum albumin (E2-BSA) produced the same effect, suggesting
      possible involvement of cell membrane receptors. ICI 182,780, a specific estrogen
      receptor (ER) antagonist, blocked the neuronal response to 17beta-estradiol and
      estradiol BSA, indicating a role of specific ERs. The present study demonstrates
      that 17beta-estradiol acutely reduces glutamate-stimulated intracellular Ca2+
      increase via ERs probably on the cell surface of the hippocampal neurons.

PMID- 15488489
TI  - Effect of reversible inactivation of the supramammillary nucleus on spatial
      learning and memory in rats.
AB  - Memory includes processes such as acquisition, consolidation and retrieval.
      Reference memory (RM) and working memory (WM) are two kinds of memory that can be
      assessed in rodents using spatial tasks, especially using the Morris water maze.
      The Morris water maze is particularly sensitive to hippocampal lesions. The
      supramammillary nucleus (SuM) has strong links with the hippocampus and septum.
      The role of the SuM on spatial learning is controversial. In the present study,
      involvement of SuM in the different steps of spatial RM and WM was investigated
      in the Morris water maze using reversible inactivation of SuM with lidocaine.
      Lidocaine (0.5 microl, 4%) was injected into the SuM through a guide cannula
      implanted above the SuM. The rats were trained on RM and WM versions of the
      Morris water maze. SuM was inactivated before training or immediately after
      training or before the probe trial of retrieval tests. Reversible inactivation of
      the SuM impaired consolidation of RM, and of consolidation and retrieval of WM.
      Therefore, it seems that activity of SuM neurons plays a role in spatial RM and
      WM learning and memory in the rat.

PMID- 15488488
TI  - Sensitivity of thalamic GABAergic currents to clonazepam does not differ between
      control and genetic absence epilepsy rats.
AB  - Mutations in GABA-A receptor subunits have been reported in a number of
      idiopathic generalized epilepsies including childhood absence epilepsy. One of
      these mutations is located within a high-affinity benzodiazepine-binding domain,
      and clonazepam is clinically used as an anti-absence drug. The intrathalamic loop
      consisting of the GABAergic neurons of the nucleus reticularis thalami (NRT) and
      the thalamocortical (TC) neurons of sensory thalamic nuclei plays an essential
      role in spike and wave discharges. In a well-established genetic model of absence
      epilepsy (Genetic Absence Epilepsy rat from Strasbourg, GAERS), systemic
      injections of benzodiazepines have been shown to suppress spike-and-waves
      discharges. The aim of this study, therefore, was to determine whether the
      sensitivity of GABAergic synaptic currents to clonazepam in NRT and TC neurons
      was different in GAERS and non-epileptic control (NEC) rats. In both pre-seizure
      GAERS and NEC clonazepam (100 nM) had no effect on the mIPSCs recorded from TC
      neurons while it increased the decay time constant of the mIPSCs recorded in NRT
      neurons by a similar amount in GAERS (54.5+/-5%) and NEC (50.7+/-5%). Similar
      results have been obtained in the presence of 100 microM Cd2+, showing that the
      effect of clonazepam did not occur via modulation of voltage-activated Ca2+
      currents. These results are relevant to understand that in GAERS, the clonazepam
      anti-absence actions cannot be fully explained by the enhancement of the intra
      NRT inhibition and the modulation of the GABAergic synaptic currents in other
      brain areas, in particular the cortex, must be taken into consideration.

PMID- 15488490
TI  - Ingestive behaviors and metabolic fuels after central injections of 5-HT1A and 5
      HT1D/1B receptors agonists in the pigeon.
AB  - The effects of intracerebroventricular injections of 8-OH-DPAT (a 5-HT1A agonist;
      3, 15 or 30 nmol) or GR46611 (a 5-HT1B/1D agonist; 3, 15 or 30 nmol) on feeding,
      drinking, preening and sleep-like behaviors were investigated in free-feeding
      (FF) pigeons. The effects of these 5-HT agonists on blood glucose and free fatty
      acids levels were also examined. Injections of 8-OH-DPAT evoked intense lipolytic
      and dipsogenic effects, but failed to affect feeding, non-ingestive behaviors and
      glycemic levels. On the other hand, GR46611 evoked significant increases in food
      intake (at the higher dose), as well as lipolytic and hyperglycemic effects, but
      left drinking and other non-ingestive behaviors unchanged. These effects are
      opposed to those found in rodents, and may be associated with the diverse,
      species-specific nature and distribution of these receptors, underscoring the
      need to examine the functional aspects of the 5-HT1 receptor family in a more
      extensive range of non-rodent species.

PMID- 15488491
TI  - Opioid receptor subtype antagonists differentially alter GABA agonist-induced
      feeding elicited from either the nucleus accumbens shell or ventral tegmental
      area regions in rats.
AB  - Food intake is significantly increased by administration of either GABAA (e.g.,
      muscimol) or GABAB (e.g., baclofen) agonists into either the shell region of the
      nucleus accumbens (NAC) or the ventral tegmental area (VTA); these responses are
      selectively blocked by pretreatment with corresponding GABAA and GABAB
      antagonists. Previous studies found that a single dose (5 microg) of the general
      opioid antagonist, naltrexone reduced feeding elicited by muscimol, but not
      baclofen in the NAC shell, and reduced feeding elicited by baclofen, but not
      muscimol in the VTA. The present study compared feeding responses elicited by
      either muscimol or baclofen in either the VTA and NAC shell following
      pretreatment with equimolar doses of selective mu (0.4, 4 microg), delta (0.4, 4
      microg), or kappa (0.6, 6 microg) opioid receptor subtype antagonists. Muscimol
      (25 ng) and baclofen (200 microg) each significantly and equi-effectively
      increased food intake over 4 h following VTA or NAC shell microinjections.
      Muscimol-induced feeding elicited from the VTA was significantly enhanced by mu
      or delta antagonists, and was significantly reduced by kappa antagonists.
      Baclofen-induced feeding elicited from the VTA was significantly reduced by mu or
      kappa, but not delta antagonists. Muscimol-induced feeding elicited from the NAC
      was significantly reduced by either mu, kappa or delta antagonists. Baclofen
      induced feeding elicited from the NAC was significantly reduced by kappa or
      delta, but not mu antagonists. These data indicate differential opioid receptor
      subtype antagonist-induced mediation of GABA receptor subtype agonist-induced
      feeding elicited from the VTA and NAC shell. This is consistent with previously
      demonstrated differential GABA receptor subtype antagonist-induced mediation of
      opioid-induced feeding elicited from these same sites. Thus, functional
      relationships exist for the elaborate anatomical and physiological interactions
      between these two neurochemical systems in the VTA and NAC shell.

PMID- 15488492
TI  - Neuroprotection by fructose-1,6-bisphosphate involves ROS alterations via p38
      MAPK/ERK.
AB  - Fructose-1,6-bisphosphate (FBP) is a glucose metabolism intermediate that shows a
      neuroprotective action in animal models of ischemia and other injuries. The
      intracellular mechanism of FBP on neuroprotection has not been previously
      defined. Here, we examined whether FBP has a neuroprotective effect against
      excitotoxicity, and whether it affects the production of reactive oxygen species
      (ROS), which are involved in the MAPK pathway in cortical neurons. FBP prevented
      neuronal death in a dose-dependent manner following 24 h of treatment with the
      excitotoxin, NMDA. After 8 h of NMDA treatment, we observed FBP-induced
      inhibition of the production of intracellular ROS, and at the earlier time FBP
      suppressed NMDA-induced p-p38 and p-ERK expression. In addition, MAPK inhibitors
      reduced NMDA-induced excitotoxicity and also ROS production. Taken together, our
      results suggest that the neuroprotective effects of FBP could be explained by
      down-regulation of free radical production through the p38MAPK/ERK pathway.

PMID- 15488493
TI  - Heat shock induces neurite outgrowth in PC12m3 cells via the p38 mitogen
      activated protein kinase pathway.
AB  - We investigated the role of the p38 mitogen-activated protein kinase (MAPK)
      pathway in heat-shock-induced neurite outgrowth of PC12 mutant cells in which
      nerve growth factor (NGF)-induced neurite outgrowth is impaired. When cultures of
      the PC12 mutant (PC12m3) cells were exposed to heat stress at 44 degrees C for 10
      min, activity of p38 MAPK increased and neurite outgrowth was greatly enhanced.
      The neurite extension was inhibited by the p38 MAPK inhibitor BS203580. Longer
      heat treatment of PC12m3 cells provoked cell death, which was enhanced by
      SB203580. These findings suggest that heat-induced activation of p38 MAPK is
      responsible for the neurite outgrowth and survival of PC12m3 cells.

PMID- 15488494
TI  - Central injection of senktide, an NK3 receptor agonist, or neuropeptide Y
      inhibits LH secretion and induces different patterns of Fos expression in the rat
      hypothalamus.
AB  - Arcuate neurokinin B (NKB) neurons express estrogen receptor-alpha and are
      strongly modulated by gonadal steroids. Although numerous studies suggest that
      NKB neurons participate in the reproductive axis, there is no information on the
      regulation of luteinizing hormone (LH) secretion by NKB or its receptor, NK3. In
      the present study, we determined if central injection of senktide, a selective
      NK3 receptor agonist, would alter serum LH in ovariectomized, estrogen-primed
      rats. The effects of senktide were compared to neuropeptide Y (NPY), a well
      characterized modulator of LH secretion. Saline, senktide, or NPY was injected
      into the lateral ventricle of unanesthetized rats and serial blood samples were
      collected for LH radioimmunoassay. The rats were sacrificed 90 min after
      injection and the brains were removed and processed for Fos immunocytochemistry.
      A significant inhibition of serum LH was observed from 30 to 90 min after
      injection of senktide relative to saline controls. In the senktide-injected rats,
      the inhibition of serum LH was accompanied by increased Fos expression in the
      medial preoptic area and arcuate nucleus--two reproductive control centers.
      Senktide also induced Fos in the paraventricular nuclei (PVN) and supraoptic
      nuclei (SON). Injection of NPY also inhibited serum LH but increased Fos
      expression only in the PVN and SON. This study provides the first demonstration
      of alterations in LH secretion by an NK3 receptor agonist. These data, combined
      with the induction of Fos in medial preoptic and arcuate neurons, strongly
      support the hypothesis that NKB neurons play a role in the regulation of
      gonadotropin secretion.

PMID- 15488495
TI  - AChE-rich magnopyramidal neurons have a left-right size asymmetry in Broca's
      area.
AB  - Acetylcholinesterase-rich neurons (AChERN) are a particular group of pyramidal
      neurons, displaying a specific laminar and ontogenetic pattern in the cerebral
      cortex of human and nonhuman primates. Using histochemistry and morphometrical
      methods, we have found a layer 3 magnopyramidal AChERN left-right size asymmetry
      restricted to Brodmann's area 45, a component of Broca's language area. This
      structural feature could be related to functional lateralization associated to
      syntactic processing and phonological working memory, and is consistent with a
      non-cholinergic role of AChE possibly linked to neuroplastic processes in the
      human neocortex.

PMID- 15488496
TI  - Traumatic brain injury and stabilisation of long bone fractures: an update.
AB  - In the era of "damage control orthopaedics", the timing and type of stabilisation
      of long bone fractures in patients with associated severe traumatic brain injury
      has been a topic of lively debate. This review summarises the current evidence
      available regarding the management of these patients. There appear to be no clear
      treatment guidelines. Irrespective of the treatment protocol followed, if
      secondary brain damage is to be avoided at all times, ICP monitoring should be
      used, both in the intensive care unit and in the operating theatre during
      surgical procedures, since aggressive ICP management appears to be related to
      improved outcomes. Treatment protocols should be based on the individual clinical
      assessment, rather than mandatory time policies for fixation of long bone
      fractures.

PMID- 15488497
TI  - L-selectin shows time and gender dependency in association with MODS.
AB  - BACKGROUND: Recent investigations have demonstrated gender related immunologic
      alterations after trauma. These complications arise due to polymorphonuclear
      granulocytes (PMN) interacting with endothelium via L-selectin. Therefore, the
      purpose of this study was to investigate gender related differences in the
      expression of L-selectin in relation to posttraumatic multiple organ dysfunction
      syndrome (MODS). METHODS: Multiply injured patients were prospectively entered in
      the study. MODS was determined using the Denver score. The concentration of L
      selectin on the surface of PMN was determined using flow cytometry during a 14
      days' period. RESULTS: 48 patients were included in the study. The kinetics of L
      selectin were different comparing male and female patients. Male patients with
      MODS initially showed a rapid decrease of surface L-selectin from 80 to 20 ng/ml.
      A return to admission levels was related to MODS. Male patients without MODS
      displayed elevated L-selectin levels up to 140 ng/ml. Female patients, however,
      all showed an initial rapid decrease of L-selectin to 20 ng/ml. Women who
      developed posttraumatic MODS had significantly increased levels up to 110 ng/ml
      before development of MODS developed. CONCLUSIONS: We feel that a gender related
      dimorphism in the initial L-selectin expression following trauma exists and is
      associated with MODS. These findings indicate new therapeutic means for the
      treatment of MODS. Therapies should be timely and gender dependently coordinated.

PMID- 15488498
TI  - Controlling bleeding from superficial wounds by the use of topical alpha
      adrenoreceptor agonists spray. A randomized, masked, controlled study.
AB  - In an attempt to determine whether alpha adrenergic agonists sprayed directly
      over the wound are able to reduce a superficial bleeding, phenylephrine (0.25%),
      oxymetazoline (0.05 and 0.25%) and saline (0.9%) were tested in a rat model. The
      study was randomized, controlled and quantitative. A total of four incisions were
      made in each rat, and each solution was sprayed directly on the incision
      according to a specific protocol. The bleeding times were measured and summed up.
      Biases were minimized by the fact that each rat received all four solutions,
      including the control, in all possible combinations. The mean bleeding time after
      spraying phenylephrine (0.25%) was significantly shorter than the mean bleeding
      time after spraying saline (1.90 +/- 0.14 min versus 4.80 +/- 0.43 min,
      respectively, P < 0.001) and significantly shorter than the mean bleeding time
      after spraying oxymetazoline (0.05 or 0.25%: 4.46 +/- 0.54 and 5.50 +/- 0.58 min,
      respectively, P < 0.001). No statistically significant difference was found
      between the mean bleeding time after spraying oxymetazoline (0.05 or 0.25%)
      compared with saline. We conclude that sprayed phenylephrine (0.25%) can be used
      for reducing superficial bleedings. This method is simple, cost-effective, does
      not cause further trauma to the tissue, and can be used to treat several
      bleedings simultaneously (especially abrasions and lacerations) with a single
      application, without the need for direct physical contact with the bleeding
      sites. The method is apparently safe, but further studies are needed to test the
      systemic effect of the sprayed solution.

PMID- 15488499
TI  - Improving the standard of operation notes in orthopaedic and trauma surgery: the
      value of a proforma.
AB  - Comprehensive documentation of surgical procedures is an essential component of
      good medical practice, but the standard of operation notes in orthopaedic and
      trauma surgery has been notoriously poor. The value of proformas in the
      production of high standard operation notes has been demonstrated in various
      surgical specialities. We have compared the standard of documentation of
      operation notes before and after the introduction of a proforma and report a
      significant improvement (P < 0.001) with the proforma. In addition, the results
      from a neighbouring hospital where a similar proforma was in use show a sustained
      standard of documentation 5 years after it was first used.

PMID- 15488500
TI  - Delays in open fracture management: where do they occur?
AB  - We audited the delays in the management of 29 patients presenting to our
      department with 30 open fractures over a 1-year-period to ascertain where the
      most lengthy delays were occurring. Gold standard treatment is the surgical
      debridement and stabilisation of the fracture within 6h of injury. In our series
      only 14 patients achieved this standard. The lengthiest delays were in getting a
      patient to the operating theatre following orthopaedic assessment. We have
      introduced an "open fracture proforma" to highlight the time-critical nature of
      the injury in an effort to speed-up the process.

PMID- 15488501
TI  - Refinements in the technique of 'awake' electrical nerve stimulation in the
      management of chronic low ulnar nerve injuries.
AB  - The standard technique in the management of chronic low ulnar nerve injuries
      includes excision of the neuroma and reconstruction using sural nerve grafts in
      the fully anaesthetised patient. It has been shown that using this standard
      technique, disappointing results may be observed and that significant improvement
      in results could be obtained if intra-operative matching of sensory and motor
      fascicles is performed. This study reports on eight patients with chronic ulnar
      nerve injuries managed using the technique of electrical fascicular orientation
      and sural nerve grafting. In all patients, intra-operative electrical stimulation
      of the fascicles in the proximal stump was done in the awake state. Several
      refinements in technique are described including detailing pre-operative patient
      education, anaesthetic considerations and in the technique of nerve dissection.
      Assessment was done using a sensory grading system mainly based on static two
      point discrimination and a motor grading system based on intrinsic muscle
      function and key pinch power. At final follow up satisfactory sensory (S3+ or S4)
      and motor (M3 or M4) recovery was obtained in almost all cases. It was concluded
      that intra-operative electrical fascicular orientation was reliable and that our
      refinements in the technique ensured better communication with the patient during
      surgery, resulted in a smoother awakening without apprehension, and provided an
      easier nerve dissection with preservation of the blood supply of the distal nerve
      segment.

PMID- 15488502
TI  - Risk of disability due to car crashes: a review of the literature and
      methodological issues.
AB  - With improving rates of survival following road traffic injuries in many
      countries, healthy years of life lost due to crashes increasingly reflect the
      prevalence of disabling sequelae. This review examines the epidemiological
      evidence regarding the risk of disability due to car crashes, published between
      1980 and 2002. Studies of sequelae limited to specific domains (e.g. head injury,
      whiplash, psychiatric morbidity) were excluded. Of the 19 studies meeting the
      criteria for review, most focused on the prevalence of disability following
      crashes but not the association between them. Prevalence estimates of post-crash
      disability varied from 2 to 87%. The potential sources of heterogeneity included
      differences in study settings and period, duration of follow-up, and definitions
      of exposure and outcome. Methodological problems that compounded the difficulties
      in interpretation and generalisability of study findings included selection
      biases and use of non-representative samples, idiosyncratic outcome measures,
      inadequate adjustment for confounding, and the prevailing medico-legal or
      compensation context. The findings highlight the need for well-designed
      population-based epidemiological studies using validated outcome measures and
      appropriate comparison groups to determine the independent risk of disability due
      to car crashes. The review also revealed a critical need for data from low- and
      middle-income countries, the setting for over 90% of the estimated global burden
      of road traffic injury.

PMID- 15488503
TI  - Axillary artery transection following anterior shoulder dislocation: classical
      presentation and current concepts.
AB  - Injury to the axillary artery following anterior shoulder dislocation is a very
      rare occurrence. This review serves to illustrate the now classical case of an
      elderly gentleman with a recurrent dislocation, transection of the axillary
      artery and its invariable association with a severe brachial plexus lesion, which
      is the most important determinant of long-term disability. It also highlights the
      pathognomic triad of anterior shoulder dislocation, expanding axillary haematoma
      and diminished peripheral pulse, to highlight awareness of this important injury.
      The literature on this injury has been reviewed and recommendations for the
      immediate and early post-operative investigation and management have been brought
      up to date in line with current thinking.

PMID- 15488504
TI  - Anatomical considerations for percutaneous proximal humeral fracture fixation.
AB  - PURPOSE: To investigate the hypothesis that percutaneous wire fixation of
      proximal humeral fractures is prone to regional neurovascular injury. MATERIALS
      AND METHODS: 40 cadaveric shoulders had percutaneous wires inserted from anterior
      and lateral humeral shaft entry points into the humeral head. The shoulders were
      then dissected to identify the neurovascular structures in this area. RESULTS:
      The axillary nerve trunk and posterior circumflex humeral artery were found to be
      within the field of dissection. The axillary nerve was damaged on three occasions
      by the lateral wires, two of which were direct nerve penetrations. The anterior
      wires caused a single perineural injury of a terminal branch. The main
      neurovascular leash was 57 mm (range 35-70 mm) from the acromion tip laterally
      and 51 mm (range 35-85 mm) anteriorly, with a width of 6 mm (range 4-13 mm)
      laterally, and 12 mm (range 7-15 mm) anteriorly. CONCLUSIONS: Percutaneous wire
      stabilisation is an attractive fixation option but this study highlights the
      close proximity of the important neurovasculature. Such fixation should be
      performed utilising a limited open approach, with dissection to bone under direct
      vision, with the subsequent use of a drill-sleeve for soft-tissue protection.

PMID- 15488505
TI  - The limited-contact dynamic compression plate in the management of proximal
      humeral non-union.
AB  - Non-union is an uncommon but troublesome complication of proximal humeral
      fractures. A number of surgical techniques have been reported. We describe the
      use of a contoured limited-contact dynamic compression plate in the surgical
      management of proximal humeral non-union.

PMID- 15488506
TI  - Fixion nails for humeral fractures.
AB  - Humeral fractures in the setting of multi-trauma are usually managed with
      internal fixation. We prospectively followed nine patients treated with an
      expandable nail (Fixion, DiscoTech, Medical Technologies, Herzliya, Israel),
      until union. Internal fixation rapidly stabilises the injured limb, and the lack
      of distal cross-bolting in this device markedly reduced our operative time. There
      were no complications in our series and there was evidence of clinical and
      radiological union within 6 months. We found the nail easy to use and effective
      in this clinical setting.

PMID- 15488507
TI  - Surgical treatment of acute displaced fractures of adult distal humerus with
      reconstruction plate.
AB  - We evaluated the results of the use of AO reconstruction plates in the open
      reduction and internal fixation of acute displaced fractures of the adult distal
      humerus. This was a retrospective study of such patients where the main surgical
      strategy was open reduction and internal fixation with AO reconstruction plates.
      From 1992 to 1998, 40 patients were included. Average follow-up was 98 (60-127)
      months. All the fractures united with the union time of 11.7 (9-16) weeks. Early
      post-operative complications developed in four patients (10%), including wound
      infection in two (5%) and iatrogenic ulnar neuropathy in another two (5%). At
      follow-up, 24 (60%) patients developed grade 1 osteoarthritis and eight (20%)
      developed grade 2 osteoarthritis. Thirty-five patients (87.5%) got good to
      excellent functional results and 35 cases (87.5%) were satisfied with their
      surgical results. In conclusion, open reduction and internal fixation with AO
      reconstruction plate is very useful and effective in the treatment of displaced
      fractures of the adult distal humerus.

PMID- 15488508
TI  - Olecranon fractures in adults: factors influencing outcome.
AB  - In a retrospective, non-randomized study, we reviewed our experience with the
      operative treatment of olecranon fractures to find out which factors correlate
      with subjective complaints and functional outcome. A total of 95 consecutive
      olecranon fractures were operatively treated in our level I trauma institution
      between 1 March 1992 and 1 March 2000. Medical records and X-rays of all patients
      were evaluated. Three patients died, 23 were lost to follow-up. Fifty-eight of 69
      available patients (84.0%) were reviewed clinically and/or radiologically after a
      mean time of 36 months. Fracture type, fracture classification, associated
      lesions, technical correctness of osteosynthesis, age and comorbidity were
      analysed. Radiological end result (intraarticular steps, gaps, arthrosis),
      subjective complaints, mobility of the elbow joint and muscle strength were
      evaluated. Patients with an unstable elbow (Mayo classification Type III and
      Schatzker-Schmeling classification Type D) had a higher loss of elbow function
      than others. There was a correlation between fracture morphology (fractures Type
      C and Type D in the Schatzker-Schmeling classification) and arthrosis. There also
      was a correlation between suboptimal osteosynthesis and arthrosis. There was no
      correlation between suboptimal osteosynthesis, implant loosening and secondary
      procedures. Patients more often expressed subjective complaints and loss of
      function in activities of daily life before than after metal removal. Primary
      elbow instability and fracture morphology are prognostic factors for elbow
      function and development of arthrosis after operative treatment of olecranon
      fractures. We, therefore, recommend the classification systems of the Mayo-clinic
      or of Schatzker-Schmeling. As many patients have complaints related to the
      implants, we recommend metal removal after fracture healing.

PMID- 15488509
TI  - Unilateral hinged external fixator of the elbow in complex elbow injuries.
AB  - We present the outcome of treating complex injuries of the elbow with the
      "Orthofix" external fixator in patients where the condition of the soft tissues
      did not permit extensile surgical approach or where the internal fixation would
      not be stable enough to permit safe early joint mobilization postoperatively.
      Eight patients were treated, three with supra-intercondylar fracture in the
      presence of marked osteoporosis and five with fracture-dislocation of the elbow
      and excessive soft tissue impairment. The fixator was applied for a mean of 8.5
      weeks (5-13 weeks). Great care was taken to use the appropriate technique in
      applying the fixator, especially to define the correct centre of rotation. All
      the fractures were united, and no instability of the joint was noted. All the
      patients maintained a functional range of motion, with lack of extension less
      than 30 degrees and flexion more than 120 degrees . One patient who developed
      transient palsy of the radial nerve and two patients who developed pin track
      infection were treated with oral antibiotics. Despite the technical difficulties,
      external fixation of the elbow could be a salvage procedure in difficult cases of
      elbow trauma, where open procedures are not indicated.

PMID- 15488510
TI  - Management of Gartland's type III supracondylar fractures of the humerus in
      children: the role audit and practice guidelines.
AB  - In 1995, we audited the outcome following Gartland's type III supracondylar
      fractures of the humerus in children. Closed reduction under anaesthesia (MUA)
      and cast immobilisation was the treatment of choice, with the treatment changed
      whenever displacement occurred. The result of the audit showed that 86% of cases
      were treated with this method. The rate of re-operation was 45.6%. Cubitus varus
      deformity developed in 50% of cases. Guidelines were introduced in order to
      abandon the use of MUA and cast immobilisation for type III fractures. The
      guidelines recommended treating these fractures with rigid fixation using
      Kirchner (K) wires. A re-audit was conducted in the year 2000 to study the impact
      of introducing the guidelines. The rate of compliance was 64%. The re-audit
      showed a significant drop in the rate of re-operations from 45.6 to 17.7% (P =
      0.0043), and a significant drop in the incidence of cubitus varus from 50 to 6.6%
      ( P < 0.0001). The results of the re-audit suggest that practice guidelines can
      have a major impact on clinical practice.

PMID- 15488511
TI  - Sagittally split fracture of trapezium associated with subluxated carpo
      metacarpal joint of thumb.
AB  - Trapezial fractures are uncommon, and require careful clinical and radiological
      assessment and treatment. Poor or inadequate treatment of displaced fractures of
      trapezium can lead to long-term morbidity. We report two displaced fractures of
      the trapezium. The clinical and radiological features are discussed. Both
      fractures were treated operatively and a good functional outcome was achieved.

PMID- 15488512
TI  - Distally based dorsal metacarpal flaps: a review of a series of patients treated
      in a 6-month period.
AB  - The management of dorsal digital and hand injuries can pose a difficult problem
      to the trainee surgeon. Often repair involves using tissue from neighbouring
      digits. Our experience using local perforator flaps based on the direct cutaneous
      branch of the dorsal metacarpal arteries shows that these can be dissected and
      used successfully in the management of complex injuries of the dorsum of the hand
      and proximal phalanges. The flap has been used in a series of seven patients
      treated over a 6-month period by plastic surgery trainees with 100% success. This
      one-stage procedure resulted in good functional and aesthetic outcome and left an
      acceptable donor scar.

PMID- 15488513
TI  - Vulnerability of the radial digital neurovascular bundle of the index finger
      while using the Kaplan's volar approach for irreducible dislocation of the second
      metacarpophalangeal joint.
AB  - Irreducible dislocations of the second metacarpophalangeal joints can be
      surgically reduced using the Kaplan's volar approach or the dorsal approach. We
      report on our experience of reducing these dislocations by the Kaplans volar
      approach in nine patients. This approach was preferred since the visualisation of
      the offending volar fibrocartilagenous plate is best with the use of this
      approach. In majority of the cases (six out of nine), we found that the radial
      neurovascular bundle was displaced to lie directly over the head of the
      metacarpal. The aim of this paper is to highlight the fact that the digital
      neurovascular bundle to the radial side of the index finger is displaced over the
      head of the metacarpal in a large number of patients and any transverse volar
      incision has to be made very carefully since this neurovascular bundle lies just
      under the skin which is puckered and with almost negligible subcutaneous tissue.
      If the operating surgeon is not careful enough, then it may lead to iatrogenic
      injury to the digital neurovascular bundle with associated morbidity.

PMID- 15488514
TI  - A unique fracture pattern of the proximal phalanx in children: fractures through
      the phalangeal neck with an attached dorsal bony flange.
AB  - This paper describes a unique fracture pattern of the proximal phalanx in
      children that has not been specifically studied in the literature. Volarly, the
      fracture line passes through the phalangeal neck and then the fracture line
      passes dorsally to include a dorsal flange of the metaphysis. Fractures were
      classified into three types: type I fractures were undisplaced with no finger
      deformity; type II fractures were mildly displaced in the antero-posterior plane
      without lateral angulation or scissoring; while type III fractures were severely
      displaced or had associated lateral angulation or scissoring deformity. Over a 6
      year-period, nine cases were seen by the authors. The mechanism of injury was by
      entrapping the digit in a closing door in all cases. The mean age of patients was
      5 years. Types I and II fractures were seen in five children and all were treated
      by splinting with an excellent outcome. Two children with type III fractures were
      treated with closed reduction and either splinting (one case) or k-wire (one
      case), and both had a poor initial outcome. The remaining two children with type
      III fractures were treated with open reduction and internal fixation with an
      excellent outcome. Differences between these fractures and the classic phalangeal
      neck fractures are discussed.

PMID- 15488515
TI  - Reduced perception of pain in schizophrenia: its relevance to the clinical
      diagnosis of compartment syndrome.
AB  - An atypical presentation of compartment syndrome is reported in a chronic
      schizophrenic patient with a closed upper tibial fracture. The features of this
      case and a review of the literature pertaining to pain perception in this group
      of patients are presented to raise clinical awareness of this combination of
      disorders, which may lead to delayed treatment of a surgical emergency,
      consequent on lack of development of classic symptoms in these patients. We
      suggest continuous intracompartmental pressure monitoring, even in awake
      schizophrenic patients with injuries at risk of compartment syndrome.

PMID- 15488516
TI  - Compartment syndrome caused by suction.
AB  - Compartment syndrome is probably underdiagnosed particularly when the mechanism
      of injury is indirect. This case is unusual in that the syndrome occurred as a
      consequence of suction injury and illustrates the benefits of early tissue
      pressure measurement and surgical decompression.

PMID- 15488517
TI  - Acute on chronic peroneal compartment syndrome.

PMID- 15488518
TI  - Atraumatic forearm compartment syndrome: alert patients taking neuroleptics are
      at risk.

PMID- 15488519
TI  - Traumatic bowing of the forearm bones in roller machine injuries.
AB  - Slow bending forces created by rollers of rotating machines and acting on forearm
      bones can result in traumatic bowing even in adults. Four patients having this
      peculiar injury pattern in industrial accidents have been reported in this paper.
      Three of these had concomitant fractures of ipsilateral humerus. There were
      problems in appropriate reduction of the deformity due to the presence of
      associated overlying soft tissue injury. The literature has also been reviewed
      for this injury and 13 reports defining the injury profile, problems in
      realigning forearm bones and their subsequent maintenance have been described.
      The eventual outcome of such machine injuries has not been good due to
      persistence of some degrees of bowing and associated restriction of forearm
      rotation.

PMID- 15488520
TI  - Remodelling in a malunited phalangeal neck fracture.

PMID- 15488521
TI  - Insidious presentation of axillary artery branch avulsion after trivial blunt
      trauma.

PMID- 15488522
TI  - A protector for retrograde femoral nailing using proctoscope.
AB  - An improvised method of using a proctoscope as a protector during the reaming
      procedure for closed retrograde femoral nailing is described. This protector is
      easy to handle and can be effectively used to protect the intra-articular
      structures, patellar cartilage and patellar tendon during the reaming process.
      The protector can also help minimise the reaming bone dust spilling out into the
      joint cavity.

PMID- 15488523
TI  - Avascular necrosis of the talus after a minimally displaced neck of talus
      fracture in a 6-year-old child [Injury 31 (2000) 63-65]. Is it really unique?

PMID- 15488524
TI  - "Active" refuges can inhibit the evolution of resistance in insects towards
      transgenic insect-resistant plants.
AB  - Negative cross-resistance (NCR) toxins that hitherto have not been thought to
      have practical uses may indeed be useful in the management of resistance alleles.
      Practical applications of NCR for pest management have been limited (i) by the
      scarcity of high toxicity NCR toxins among pesticides, (ii) by the lack of
      systematic methodologies to discover and develop such toxins, as well as (iii) by
      the lack of deployment tactics that would make NCR attractive. Here we present
      the concept that NCR toxins can improve the effectiveness of refuges in delaying
      the evolution of resistance by herbivorous insect pests to transgenic host plants
      containing insecticidal toxins. In our concept, NCR toxins are deployed in the
      refuge, and thus are physically separated from the transgenic plants containing
      the primary plant-protectant gene (PPPG) encoding an insecticidal toxin. Our
      models show: (i) that use of NCR toxins in the refuge dramatically delays the
      increase in the frequency of resistance alleles in the insect population; and
      (ii) that NCR toxins that are only moderately effective in killing insects
      resistant to the PPPG can greatly improve the durability of transgenic
      insecticidal toxins. Moderately toxic NCR toxins are more effective in minimizing
      resistance development in the field when they are deployed in the refuge than
      when they are pyramided with the PPPG. We explore the potential strengths and
      weaknesses of deploying NCR toxins in refuges.

PMID- 15488525
TI  - The logic of reprobation: assessment and action rules for indirect reciprocation.
AB  - Ever since image-based models for indirect reciprocity were introduced, the
      relative merits of scoring vs. standing have been discussed to find out how
      important it is to differentiate between justified and non-justified defections.
      This is analogous to the question whether punishment can sustain cooperation even
      when it is costly. We show that an answer to this question can depend on details
      of the model, for instance concerning the probability distribution of the number
      of interactions experienced per player. We use extensive individual-based
      simulations to compare scoring, standing and other forms of assessing defections,
      and show that several forms of indirect reciprocation can robustly sustain
      cooperation. By most standards, standing is better than scoring, but nevertheless
      scoring is able to sustain cooperation in the presence of errors. The model
      presented here is based on three specifications: each player has a personal list
      of images of all co-players, a specific way of judging an observed situation, and
      a specific strategy to decide whether to cooperate or not.

PMID- 15488526
TI  - Cortically restricted production of IP3 leads to propagation of the fertilization
      Ca2+ wave along the cell surface in a model of the Xenopus egg.
AB  - The fertilization Ca2+ wave in Xenopus laevis is a single, large wave of elevated
      free cytosolic Ca2+ concentration that emanates from the point of sperm-egg
      fusion and traverses the entire diameter of the egg. This phenomenon appears to
      involve an increase in inositol-1,4,5-trisphosphate (IP3) resulting from
      interaction of the sperm and egg, which then results in the activation of the
      endoplasmic reticulum Ca2+ release machinery. We have proposed models based on a
      static elevated distribution of IP3, and dynamic [IP3], however, these models
      have suggested that the fertilization wave passes through the center of the egg.
      Complementing these earlier models, we propose a more detailed model of the
      fertilization Ca2+ wave in Xenopus eggs to explore the hypothesis that IP3 is
      produced only at or near the plasma membrane. In this case, we find that the wave
      propagates primarily through the cortex of the egg, and that Ca2+ -induced
      production of IP3 at the plasma membrane allows IP3 to propagate in advance of
      the wave. Our model includes Ca2+ -dependent production of IP3 at the plasma
      membrane and IP3 degradation. Simulations in 1 dimension and axi-symmetric 3
      dimensions illustrate the basic features of the wave.

PMID- 15488527
TI  - Modelling the movement of a soil insect.
AB  - We use a linear autoregressive model to describe the movement of a soil-living
      insect, Protaphorura armata (Collembola). Models of this kind can be viewed as
      extensions of a random walk, but unlike a correlated random walk, in which the
      speed and turning angles are independent, our model identifies and expresses the
      correlations between the turning angles and a variable speed. Our model uses data
      in x- and y-coordinates rather than in polar coordinates, which is useful for
      situations in which the resolution of the observations is limited. The movement
      of the insect was characterized by (i) looping behaviour due to autocorrelation
      and cross correlation in the velocity process and (ii) occurrence of periods of
      inactivity, which we describe with a Poisson random effects model. We also
      introduce obstacles to the environment to add structural heterogeneity to the
      movement process. We compare aspects such as loop shape, inter-loop time, holding
      angles at obstacles, net squared displacement, number, and duration of inactive
      periods between observed and predicted movement. The comparison demonstrates that
      our approach is relevant as a starting-point to predict behaviourally complex
      moving, e.g. systematic searching, in a heterogeneous landscape.

PMID- 15488528
TI  - An ordinary differential equation model for the multistep transformation to
      cancer.
AB  - Cancer is viewed as a multistep process whereby a normal cell is transformed into
      a cancer cell through the acquisition of mutations. We reduce the complexities of
      cancer progression to a simple set of underlying rules that govern the
      transformation of normal cells to malignant cells. In doing so, we derive an
      ordinary differential equation model that explores how the balance of
      angiogenesis, cell death rates, genetic instability, and replication rates give
      rise to different kinetics in the development of cancer. The key predictions of
      the model are that cancer develops fastest through a particular ordering of
      mutations and that mutations in genes that maintain genomic integrity would be
      the most deleterious type of mutations to inherit. In addition, we perform a
      sensitivity analysis on the parameters included in the model to determine the
      probable contribution of each. This paper presents a novel approach to viewing
      the genetic basis of cancer from a systems biology perspective and provides the
      groundwork for other models that can be directly tied to clinical and molecular
      data.

PMID- 15488529
TI  - Nonspecific binding of the OR repressors CI and Cro of bacteriophage lambda.
AB  - We estimate the Gibbs free energy for nonspecific binding (DeltaGNSB) to the
      Escherichia coli DNA for two regulatory proteins of the lambda phage, CI and Cro.
      By means of a statistical-mechanical approach, we calculate the cI and cro
      activities associated with the operator OR of an introduced lambda phage genome
      (prophage). In this statistical model we apply in vitro-measured binding free
      energies to fit in vivo experimental data for cI and cro activities,
      respectively, where DeltaGNSB is introduced as a free (fitting) parameter.
      Without nonspecific binding included in the model, the quality of the description
      is fairly poor, whereas data are nicely correlating with our model with
      nonspecific binding included over the entire data range. The obtained values of
      DeltaGNSB are -4.1+/-0.9 kcal/mol, for CI, and -4.2+/-0.8 kcal/mol, for Cro. In
      particular, in a lysogen (approximately 250 CI monomers per cell) we conclude
      that 86% of the total CI in the cell is nonspecifically bound, leaving on average
      around 10 CI dimers freely available in the E. coli cytoplasma. These findings
      corroborate the view that due to low free cellular particle numbers a dynamical
      analysis of genetic regulation at OR and comparable systems should include a
      stochastic component. In addition, we perform a stability analysis of the OR
      system in the presence of nonspecific binding.

PMID- 15488530
TI  - Foreignness as a matter of degree: the relative immunogenicity of peptide/MHC
      ligands.
AB  - The ability of T lymphocytes (T cells) to recognize and attack foreign invaders
      while leaving healthy cells unharmed is often analysed as a discrete self/non
      self dichotomy, with each peptide/MHC ligand classified as either self or non
      self. We argue that the ligand immunogenicity is more naturally treated as a
      continuous quantity, and show how to define and quantitate relative ligand
      immunogenicity. In our theory, self-tolerance is acquired through reduction of
      the relative immunogenicity of autoantigens, whereas xenoantigens, typically not
      presented during induction of deletional tolerance, retain a high degree of
      relative immunogenicity. Autoantigens that are not prominently presented in
      deletional tolerance likewise retain a high relative immunogenicity and remain
      essentially foreign. According to our analysis, any given autoantigen can attain
      a high level of relative immunogenicity, provided it is presented at sufficiently
      high levels. Our theory provides a quantitative tool to analyse the
      immunogenicity of tumour-associated neoantigens and the aetiology of autoimmune
      disease.

PMID- 15488531
TI  - Modeling intra-sexual competition in a sex pheromone system: how much can female
      movement affect female mating success?
AB  - Mating disruption theory predicts that high concentrations of female pheromone,
      and/or large numbers of release sites, should confuse males orienting to
      "calling" females, reduce the number of successful matings, and decrease the
      reproductive potential of the population. In this scenario, females are regarded
      as stationary point sources of pheromone. Past behavioral observations, however,
      have shown virgin female grape root borers, Vitacea polistiformis Harris,
      significantly alter their behavior in mating disruption treatments. Treated
      females call at different heights, move less before call initiation, and move
      more after call initiation than control females. Pheromone gland dragging and
      wing fanning also increase significantly during pheromone treatments. These
      behavioral differences are significant only if they alter the mating success of
      females. Because long-term field studies are impractical, we used known behavior
      of male and female GRB to build a Fortran language time step model, adding the
      effects of female movement to past models of male pheromone plume following.
      Females were distributed randomly, and then assigned a conditional movement
      strategy. If females were within the competitive portion of another female's
      plume, the downwind female moved. Except in the lowest population density tested,
      females moving upwind and crosswind when in a competing female's pheromone plume
      mated significantly more often than females remaining stationary. In all
      population simulations, mating success was significantly reduced when females
      moved downwind. These field and simulation studies provide strong evidence for
      female movement as a previously overlooked potential mechanism for resistance to
      mating disruption treatments, as well as a shaping behavior in the evolution of
      pheromone communication systems.

PMID- 15488532
TI  - A stochastic model for the mutation-selection balance in an infinite asexual
      population with a genome of fixed size.
AB  - A stochastic model is presented which describes the evolution of a genome of a
      haploid species in an infinite population. The genome is a finite set of
      elements. The elements are divided into different classes according to their
      effect on the fitness of the organism. Repeated mutations of the genome elements
      are permitted, in particular positive mutations are introduced. The distribution
      of the deleterious elements in the genome with respect to the impact on the
      fitness is given after the replication step. The steady state is fully described
      including the distribution and the fitness.

PMID- 15488533
TI  - Intrinsic noise, gene regulation and steady-state statistics in a two-gene
      network.
AB  - The intrinsic noise in a two-gene network model is analysed. The technique of the
      Fokker-Planck approximation is used to investigate the statistics of noise when
      the system state is near a stable equilibrium. This is called also the steady
      state statistics. The relative size of noise is measured by the Fano factor that
      is defined as the ratio of the variance to the mean. Our main result shows that
      in general, the noise control in a two-gene network might be a very complicated
      process, but for the repressor-repressor system that is a very important case in
      investigating the genetic switch, the relative size of noise, i.e. the Fano
      factor, must be bigger than one for both the repressor proteins.

PMID- 15488534
TI  - Incompatible mechanical properties in compact bone.
AB  - The covariation of a number of mechanical of properties, and some physical
      characteristics, of compact bones from a wide range of bones were examined.
      Young's modulus was well predicted by a combination of mineral content and
      porosity. Increasing Young's modulus was associated with: increasing stress at
      yield, increasing bending strength, and a somewhat higher resilience, tensile
      strength and fatigue strength. Contrarily, in the post-yield region a higher
      Young's modulus (and more clearly, a higher mineral content) was associated with:
      a reduced work to fracture in tension, a reduced impact strength and an increased
      notch sensitivity in impact. Increasing porosity is associated with deleterious
      effects in the pre-yield region, but has little effect in the post-yield region.
      Bone, like many other materials, is unable to have good qualities in both the pre
      and post-yield regions. Since an increase in mineral or Young's modulus is more
      potent, that is deleterious, in the post-yield than it is advantageous in the pre
      yield region, it is likely that mineral content will be selected to be slightly
      lower than would be the case if it were equally potent in both regions. As is
      usual in biology, different adaptive extremes are incompatible.

PMID- 15488535
TI  - A framework for whole-cell mathematical modeling.
AB  - The default framework for modeling biochemical processes is that of a constant
      volume reactor operating under steady-state conditions. This is satisfactory for
      many applications, but not for modeling growth and division of cells. In this
      study, a whole-cell modeling framework is developed that assumes expanding
      volumes and a cell-division cycle. A spherical newborn cell is designed to grow
      in volume during the growth phase of the cycle. After 80% of the cycle period,
      the cell begins to divide by constricting about its equator, ultimately affording
      two spherical cells with total volume equal to twice that of the original. The
      cell is partitioned into two regions or volumes, namely the cytoplasm (Vcyt) and
      membrane (Vmem), with molecular components present in each. Both volumes change
      during the cell cycle; Vcyt changes in response to osmotic pressure changes as
      nutrients enter the cell from the environment, while Vmem changes in response to
      this osmotic pressure effect such that membrane thickness remains invariant. The
      two volumes change at different rates; in most cases, this imposes periodic or
      oscillatory behavior on all components within the cell. Since the framework
      itself rather than a particular set of reactions and components is responsible
      for this behavior, it should be possible to model various biochemical processes
      within it, affording stable periodic solutions without requiring that the
      biochemical process itself generates oscillations as an inherent feature. Given
      that these processes naturally occur in growing and dividing cells, it is
      reasonable to conclude that the dynamics of component concentrations will be more
      realistic than when modeled within constant-volume and/or steady-state
      frameworks. This approach is illustrated using a symbolic whole cell model.

PMID- 15488536
TI  - Probabilistic pathway representation of cognitive information.
AB  - We present for mental processes the program of mathematical mapping which has
      been successfully realized for physical processes. We emphasize that our project
      is not about mathematical simulation of the brain's functioning as a complex
      physical system, i.e., mapping of physical and chemical processes in the brain on
      mathematical spaces. The project is about mapping of purely mental processes on
      mathematical spaces. We present various arguments--philosophic, mathematical,
      information, and neurophysiological--in favor of the p-adic model of mental
      space. p-adic spaces have structures of hierarchic trees and in our model such a
      tree hierarchy is considered as an image of neuronal hierarchy. Hierarchic neural
      pathways are considered as fundamental units of information processing. As neural
      pathways can go through the whole body, the mental space is produced by the whole
      neural system. Finally, we develop the probabilistic neural pathway model in that
      mental states are represented by probability distributions on mental space.

PMID- 15488537
TI  - Male sexual function.

PMID- 15488538
TI  - Importance of olfactory and vomeronasal systems for male sexual function.
AB  - Chemosensory cues stimulate male sexual arousal and behavior. The main olfactory
      system has an important role in attracting males to estrous females, and the
      vomeronasal receptors are important for activating accessory olfactory pathways
      that engage mating behavior in a sexually dimorphic manner. The gonadotropin
      releasing hormone (GnRH) neurons like the vomeronasal organ (VNO) neurons take
      their origin in the olfactory placode and migrate to the basal forebrain along
      pathfinder axons that take their origin in the developing VNO. The maturation of
      both systems is synchronized in time such that the early postnatal testosterone
      surge masculinizes the VNO neural relay en route to the medio preoptic area
      (MPOA). Although VNO slices and VNO receptor neurons in culture respond to
      volatile odors, in vivo electrophysiological recordings at the first relay in the
      accessory olfactory bulb (AOB) are silent until the male makes active nuzzling
      investigations of the female. The VNO neurons may therefore respond to volatiles
      that are transported into the organ on carrier peptides that themselves may play
      a part in receptor activation. In the context of modern molecular phylogenetic
      studies, it is becoming less likely that pheromones acting via the VNO have any
      part to play in human sexual behavior, but the possibility exists for conserved
      VNO genes influencing human reproduction via fertilization.

PMID- 15488539
TI  - Neural control of erection.
AB  - Penile erection is a vascular event controlled by the autonomic nervous system.
      The spinal cord contains the autonomic preganglionic neurons that innervate the
      penile erectile tissue and the pudendal motoneurons that innervate the perineal
      striated muscles. Sympathetic pathways are anti-erectile, sacral parasympathetic
      pathways are pro-erectile, and contraction of the perineal striated muscles upon
      activity of the pudendal nerves improves penile rigidity. Spinal neurons
      controlling erection are activated by information from peripheral and supraspinal
      origin. Both peripheral and supraspinal information is capable of either
      eliciting erection or modulating or inhibiting an erection already present.
      Sensory information from the genitals is a potent activator of pro-erectile
      spinal neurons and elicits reflexive erections. Some pre-motor neurons of the
      medulla, pons and diencephalon project directly onto spinal sympathetic,
      parasympathetic and pudendal motoneurons. They receive in turn sensory
      information from the genitals. These spinal projecting pathways release a variety
      of neurotransmitters, including biogenic amines (serotonin, dopamine,
      noradrenaline, and adrenaline) and peptides that, through interactions with many
      receptor subtypes, exert complex effects on the spinal network that controls
      penile erection. Some supraspinal structures (e.g. the paraventricular nucleus
      and the medial preoptic area of the hypothalamus, the medial amygdala), whose
      roles in erection have been demonstrated in animal models, may not project
      directly onto spinal pro-erectile neurons. They are nevertheless prone to
      regulate penile erection in more integrated and coordinated responses of the
      body, as those occurring during sexual behavior. The application of basic and
      clinical research data to treatment options for erectile dysfunction has recently
      proved successful. Pro-erectile effects of phosphodiesterase type 5 inhibitors,
      acting in the penis, and of melanocortin agonists, acting in the brain,
      illustrate these recent developments.

PMID- 15488540
TI  - Central regulation of ejaculation.
AB  - Ejaculation is a reflex mediated by a spinal control center, referred to as a
      spinal ejaculation generator. This spinal ejaculation generator coordinates
      sympathetic, parasympathetic and motor outflow to induce the two phases of
      ejaculation, i.e., emission and expulsion. In addition, the spinal ejaculation
      generator integrates this outflow with inputs that are related to the summation
      of sexual activity prior to ejaculation that are required to trigger ejaculation.
      Recently, a group of spinothalamic neurons in the lumbar spinal cord (LSt cells)
      were demonstrated to comprise an integral part of the spinal ejaculation
      generator. Specifically, lesions of LSt cells completely ablate ejaculatory
      function. Moreover, LSt cells are activated following ejaculation, but not
      following other components of sexual behavior. Furthermore, based on their
      relationship with autonomic nuclei, motoneurons and genital sensory inputs, LSt
      cells are also in the ideal anatomical position to integrate sensory inputs and
      autonomic and motor outflow. Additionally, the spinal ejaculation generator is
      under inhibitory and excitatory influence of supraspinal sites, including the
      nucleus paragigantocellularis (nPGi), the paraventricular nucleus of the
      hypothalamus (PVN) and the medial preoptic area (MPOA). Finally, sensory
      information related to ejaculation is processed in the spinal cord and brain,
      possibly contributing to the rewarding properties of ejaculation. One candidate
      pathway for relay of ejaculation-related cues consists of LSt cells and their
      projections to the parvocellular subparafascicular thalamic nucleus. Moreover,
      neural activation specifically related to ejaculation is observed in the brain
      and may reflect of processing of ejaculation-related sensory cues.

PMID- 15488541
TI  - Of mice and missing data: what we know (and need to learn) about male sexual
      behavior.
AB  - With recent advances in molecular genetics, the popularity of mice as subjects
      for behavioral neuroscience is increasing at an exponential rate. Unfortunately,
      the existing body of knowledge on sexual behavior in male mice is not large and
      many basic gaps exist. The assumption that what is true of rats is also true of
      mice is a dangerous one that can misdirect and, in the worst case, impede
      progress. We summarize the current knowledge about the sexual behavior of male
      mice, with an emphasis on hormonal bases of these behaviors. Behavioral
      differences between strains, developmental actions of steroids, activational
      actions of steroids given peripherally and in the brain, and data generated in
      various receptor knockout and related mice are discussed. In addition,
      suggestions are made for the standardization of experimental protocols used in
      investigations of the sexual physiology and behavior of male mice in order to
      facilitate between-experiment and between-laboratory comparisons and to expedite
      the growth of knowledge in this area.

PMID- 15488542
TI  - Sexual partner preference, hypothalamic morphology and aromatase in rams.
AB  - The male-oriented ram is a unique and valuable animal model for the study of
      hormonal, developmental and genetic contributions to sexual partner preference.
      Unlike most other mammalian models that are in use currently, variations in
      sexual attraction occur spontaneously in domestic ram populations. It is
      estimated that as many as 8-10% of rams exhibit a sexual partner preference for
      other males, classifying them as male-oriented rams. Studies have failed to
      identify any compelling social factors that can predict or explain the variations
      in sexual partner preferences of rams. Nor is there consensus on the endocrine
      and sensory responsiveness of male-oriented rams to other rams. However, a number
      of studies have reported differences in brain structure and function between male
      oriented and female-oriented rams, suggesting that sexual partner preferences are
      neurologically hard-wired. Recently, we identified a sexually dimorphic nucleus
      (oSDN) in the sheep preoptic area-anterior hypothalamus. The oSDN is larger in
      female-oriented rams than in male-oriented rams and similar in size in male
      oriented rams and ewes. In addition, mRNA levels for aromatase in the oSDN were
      higher in males than in females and were higher in female-oriented rams than in
      male-oriented rams. These results suggest a relationship between steroid
      hormones, specifically estrogens and oSDN morphology. In this review, we provide
      an overview of sexual behavior in rams and discuss the multiple factors that may
      contribute to the development and adult expression of same-sex partner
      preferences in rams.

PMID- 15488543
TI  - Preoptic aromatase modulates male sexual behavior: slow and fast mechanisms of
      action.
AB  - In many species, copulatory behavior and appetitive (anticipatory/motivational)
      aspects of male sexual behavior are activated by the action in the preoptic area
      of estrogens locally produced by testosterone aromatization. Estrogens bind to
      intracellular receptors, which then act as transcription factors to activate the
      behavior. Accordingly, changes in aromatase activity (AA) result from slow
      steroid-induced modifications of enzyme transcription. More recently, rapid
      nongenomic effects of estrogens have been described and evidence has accumulated
      indicating that AA can be modulated by rapid (minutes to hour) nongenomic
      mechanisms in addition to the slower transcriptional changes. Hypothalamic AA is
      rapidly down-regulated in conditions that enhance protein phosphorylation, in
      particular, increases in the intracellular calcium concentration, such as those
      triggered by neurotransmitter (e.g., glutamate) activity. Fast changes in brain
      estrogens can thus be caused by aromatase phosphorylation as a result of changes
      in neurotransmission. In parallel, recent studies demonstrate that the
      pharmacological blockade of AA by specific inhibitors rapidly (within 15-45 min)
      down-regulates motivational and consummatory aspects of male sexual behavior in
      quail while injections of estradiol can rapidly increase the expression of
      copulatory behavior. These data collectively support an emerging concept in
      neuroendocrinology, namely that estrogen, locally produced in the brain,
      regulates male sexual behavior via a combination of genomic and nongenomic
      mechanisms. Rapid and slower changes of brain AA match well with these two modes
      of estrogen action and provide temporal variations in the estrogen's
      bioavailability that can support the entire range of established effects for this
      steroid.

PMID- 15488544
TI  - Steroid hormone masculinization of neural structure in rats: a tale of two
      nuclei.
AB  - We review the mechanisms by which steroid hormones masculinize two different
      regions of the central nervous system (CNS) in rats. Although in both cases,
      androgens induce a male phenotype, the detailed mechanisms are remarkably
      different in the two models. In the spinal nucleus of the bulbocavernosus (SNB),
      testosterone must be present during the perinatal period to spare motoneurons and
      their target muscles from cell death. This masculinization of the SNB system is
      through activation of androgen receptors, because XY rats with a defective gene
      for the androgen receptor fail to develop a masculine SNB system. Interestingly,
      the motoneurons are spared by androgen, even though they themselves do not
      possess androgen receptors during the critical period for their survival. Thus,
      steroids can act on one part of the body to secondarily masculinize the CNS. In
      the posterodorsal aspect of the medial amygdala (MePD), testosterone can induce
      masculine development even in adulthood, indicating that there is no critical
      period for steroids to affect sexual differentiation of this system. In the case
      of the MePD, both estrogen receptors and androgen receptors appear to mediate
      testosterone's masculinizing influence on neural structure. The extended neural
      plasticity of the MePD may reflect annual "reorganization" of the brain in the
      seasonally breeding ancestors of laboratory rats.

PMID- 15488545
TI  - Reinforcing aspects of androgens.
AB  - Are androgens reinforcing? Androgenic-anabolic steroids (AAS) are drugs of abuse.
      They are taken in large quantities by athletes and others to increase
      performance, often with negative long-term health consequences. As a result, in
      1991, testosterone was declared a controlled substance. Recently, Brower [K.J.
      Brower, Anabolic steroid abuse and dependence. Curr. Psychiatry Rep. 4 (2002) 377
      387.] proposed a two-stage model of AAS dependence. Users initiate steroid use
      for their anabolic effects on muscle growth. With continued exposure, dependence
      on the psychoactive effects of AAS develops. However, it is difficult in humans
      to separate direct psychoactive effects of AAS from the user's psychological
      dependence on the anabolic effects of AAS. Thus, studies in laboratory animals
      are useful to explore androgen reinforcement. Testosterone induces a conditioned
      place preference in rats and mice, and is voluntarily consumed through oral,
      intravenous, and intracerebroventricular self-administration in hamsters. Active,
      gonad-intact male and female hamsters will deliver 1 microg/microl testosterone
      into the lateral ventricles. Indeed, some individuals self-administer
      testosterone intracerebroventricularly to the point of death. Male rats develop a
      conditioned place preference to testosterone injections into the nucleus
      accumbens, an effect blocked by dopamine receptor antagonists. These data suggest
      that androgen reinforcement is mediated by the brain. Moreover, testosterone
      appears to act through the mesolimbic dopamine system, a common substrate for
      drugs of abuse. Nonetheless, androgen reinforcement is not comparable to that of
      cocaine or heroin. Instead, testosterone resembles other mild reinforcers, such
      as caffeine, nicotine, or benzodiazepines. The potential for androgen addiction
      remains to be determined.

PMID- 15488546
TI  - Dopamine and serotonin: influences on male sexual behavior.
AB  - Steroid hormones regulate sexual behavior primarily by slow, genomically mediated
      effects. These effects are realized, in part, by enhancing the processing of
      relevant sensory stimuli, altering the synthesis, release, and/or receptors for
      neurotransmitters in integrative areas, and increasing the responsiveness of
      appropriate motor outputs. Dopamine has facilitative effects on sexual
      motivation, copulatory proficiency, and genital reflexes. Dopamine in the
      nigrostriatal tract influences motor activity; in the mesolimbic tract it
      activates numerous motivated behaviors, including copulation; in the medial
      preoptic area (MPOA) it controls genital reflexes, copulatory patterns, and
      specifically sexual motivation. Testosterone increases nitric oxide synthase in
      the MPOA; nitric oxide increases basal and female-stimulated dopamine release,
      which in turn facilitates copulation and genital reflexes. Serotonin (5-HT) is
      primarily inhibitory, although stimulation of 5-HT(2C) receptors increases
      erections and inhibits ejaculation, whereas stimulation of 5-HT(1A) receptors has
      the opposite effects: facilitation of ejaculation and, in some circumstances,
      inhibition of erection. 5-HT is released in the anterior lateral hypothalamus at
      the time of ejaculation. Microinjections of selective serotonin reuptake
      inhibitors there delay the onset of copulation and delay ejaculation after
      copulation begins. One means for this inhibition is a decrease in dopamine
      release in the mesolimbic tract.

PMID- 15488547
TI  - The role of oxytocin and the paraventricular nucleus in the sexual behaviour of
      male mammals.
AB  - The paraventricular nucleus of the hypothalamus contains the cell bodies of a
      group of oxytocinergic neurons projecting to extrahypothalamic brain areas and to
      the spinal cord, which are involved in the control of erectile function and
      copulation. In male rats, these neurons can be activated by dopamine, excitatory
      amino acids, nitric oxide (NO), hexarelin analogue peptides and oxytocin itself
      to induce penile erection and facilitate copulation, while their inhibition by
      gamma-aminobutyric acid (GABA) and GABA agonists and by opioid peptides and
      opiate-like drugs inhibits sexual responses. The activation of paraventricular
      oxytocinergic neurons by dopamine, oxytocin, excitatory amino acids and hexarelin
      analogue peptides is apparently mediated by the activation of nitric oxide (NO)
      synthase. NO in turn activates, by a mechanism that is as yet unidentified, the
      release of oxytocin from oxytocinergic neurons in extrahypothalamic brain areas.
      Paraventricular oxytocinergic neurons and mechanisms similar to those reported
      above are also involved in the expression of penile erection in physiological
      contexts, namely, when penile erection is induced in the male by the presence of
      an inaccessible receptive female, which is considered a model for psychogenic
      impotence in man, as well as during copulation. These findings show that
      paraventricular oxytocinergic neurons projecting to extrahypothalamic brain areas
      and to the spinal cord and the paraventricular nucleus play an important role in
      the control of erectile function and male sexual behaviour in mammals.

PMID- 15488548
TI  - Neurochemical regulation of pair bonding in male prairie voles.
AB  - Pair bonding represents social attachment between mates and is common among
      monogamous animals. The prairie vole (Microtus ochrogaster) is a monogamous
      rodent in which mating facilitates pair bond formation. In this review, we first
      discuss how prairie voles have been used as an excellent model for
      neurobiological studies of pair bonding. We then primarily focus on male prairie
      voles to summarize recent findings from neuroanatomical, neurochemical, cellular,
      molecular, and behavioral studies implicating vasopressin (AVP), oxytocin (OT),
      and dopamine (DA) in the regulation of pair bonding. Possible interactions among
      these neurochemicals in the regulation of pair bonding, the brain areas important
      for pair bond formation, and potential sexually dimorphic mechanisms underlying
      pair bonding are also discussed. As analogous social bonds are formed by humans,
      investigation of the neurochemical regulation of pair bond formation in prairie
      voles may be beneficial for our understanding of the mechanisms associated with
      normal and abnormal social behaviors in humans.

PMID- 15488549
TI  - Hormonal regulation of brain circuits mediating male sexual behavior in birds.
AB  - Male sexual behavior in both field and laboratory settings has been studied in
      birds since the 19th century. Birds are valuable for the investigation of the
      neuroendocrine mechanisms of sexual behavior, because their behavior can be
      studied in the context of a large amount of field data, well-defined neural
      circuits related to reproductive behavior have been described, and the avian
      neuroendocrine system exhibits many examples of marked plasticity. As is the case
      in other taxa, male sexual behavior in birds can be usefully divided into an
      appetitive phase consisting of variable behaviors (typically searching and
      courtship) that allow an individual to converge on a functional outcome,
      copulation (consummatory phase). Based primarily on experimental studies in ring
      doves and Japanese quail, it has been shown that testosterone of gonadal origin
      plays an important role in the activation of both of these aspects of male sexual
      behavior. Furthermore, the conversion of androgens, such as testosterone, in the
      brain to estrogens, such as 17beta-estradiol, is essential for the full
      expression of male-typical behaviors. The localization of sex steroid receptors
      and the enzyme aromatase in the brain, along with lesion, hormone implant and
      immediate early gene expression studies, has identified many neural sites related
      to the control of male behavior. The preoptic area (POA) is a key site for the
      integration of sensory inputs and the initiation of motor outputs. Furthermore,
      prominent connections between the POA and the periaqueductal gray (PAG) form a
      node that is regulated by steroid hormones, receive sensory inputs and send
      efferent projections to the brainstem and spinal cord that activate male sexual
      behaviors. The sensory inputs regulating avian male sexual responses, in contrast
      to most mammalian species, are primarily visual and auditory, so a future
      challenge will be to identify how these senses impinge on the POA-PAG circuit.
      Similarly, most avian species do not have an intromittent organ, so the
      projections from the POA-PAG to the brainstem and spinal cord that control sexual
      reflexes will be of particular interest to contrast with the well characterized
      rodent system. With this knowledge, general principles about the organization of
      male sexual circuits can be elucidated, and comparative studies relating known
      species variation in avian male sexual behaviors to variation in neural systems
      can be pursued.

PMID- 15488550
TI  - Evolutionary insights into the regulation of courtship behavior in male
      amphibians and reptiles.
AB  - Comparative studies of species differences and similarities in the regulation of
      courtship behavior afford an understanding of evolutionary pressures and
      constraints shaping reproductive processes and the relative contributions of
      hormonal, genetic, and ecological factors. Here, we review species differences
      and similarities in the control of courtship and copulatory behaviors in male
      amphibians and reptiles, focusing on the role of sex steroid hormones, the
      neurohormone arginine vasotocin (AVT), and catecholamines. We discuss species
      differences in the sensory modalities used during courtship and in the neural
      correlates of these differences, as well as the value of particular model systems
      for neural evolution studies with regard to reproductive processes. For example,
      in some genera of amphibians (e.g., Ambystoma) and reptiles (e.g.,
      Cnemidophorus), interspecific hybridizations occur, making it possible to compare
      the ancestral with the descendant species, and these systems provide a window
      into the process of behavioral and neural evolution as well as the effect of
      genome size. Though our understanding of the hormonal and neural correlates of
      mating behavior in a variety of amphibian and reptilian species has advanced
      substantially, more studies that manipulate hormone or neurotransmitter systems
      are required to assess the functions of these systems.

PMID- 15488551
TI  - Sexual behavior, reproductive physiology and sperm competition in male mammals.
AB  - Sperm competition involves competition between the gametes of two or more males
      of a species for fertilization of a given set of ova. Sperm competition is
      widespread among mammals, as in many other groups of vertebrates. Effects of
      sexual selection, via sperm competition, upon the evolution of reproductive
      physiology and behavior are much better understood in invertebrates (and
      especially in insects) than is the case for mammals. However, if the reproductive
      organs of male mammals are viewed as an integrated system for production and
      delivery of spermatozoa (and accessory glandular secretions) to females, then it
      is logical to assume that sperm competition might influence the evolution of all
      parts of the system, as well as associated physiological mechanisms (e.g.,
      testicular endocrinology) and behavior (e.g., copulatory patterns). Here we
      analyze and review relationships between mating systems, relative testes sizes
      and sperm morphology, phallic morphology, circulating testosterone levels and
      sexual behavior in male mammals.

PMID- 15488552
TI  - PET imaging I.

PMID- 15488553
TI  - PET: a revolution in medical imaging.
AB  - FDG-PET has had remarkable influence on the assessment of physiologic and
      pathologic states. The authors predict that FDG-PET imaging could soon become the
      most common procedure used by nuclear medicine laboratories and could remain so
      for an extended period of time. The power of molecular imaging lies in the vast
      potential for using biochemical and pharmacologic probes to extend applications
      arising from an understanding of cell biology to a large number of well
      characterized pathologic states. Molecular imaging based upon tracer kinetics
      with positron-emitting radiopharmaceuticals could become the main source of
      information for the management of cancer patients. In that case, nuclear medicine
      procedures might become the most common imaging studies performed in the practice
      of medicine. This speculation is not farfetched when one realizes the enormous
      change that a single biologically important compound, FDG, has brought to the
      medical arena. The major challenge today is to attract the highly qualified
      individuals and to secure the resources needed to harness the opportunities in
      the specialty of molecular imaging.

PMID- 15488554
TI  - PET instrumentation.
AB  - PET is a nuclear medicine imaging modality and belongs to the family of emission
      CT, which also includes single-photon emission CT. PET measures the physiologic
      function inside the human body by measuring the concentration of a radioactively
      labeled compound that is taken up by and accumulated in the body's organs. This
      article discusses the instrumentation used in PET.

PMID- 15488555
TI  - PET/CT scanner instrumentation, challenges, and solutions.
AB  - PET/CT scanners offer a hardware solution for aligning and viewing functional and
      anatomic images that is immune to many of the errors in strictly software
      registration techniques. Moreover, PET attenuation-corrected emission scans
      benefit from the use of the onboard CT for fast, low-noise attenuation
      correction. Along with the significant improved localization and reduced
      acquisition time, PET/CT scanners also introduce new instrumentation challenges
      ranging from patient movement to quantitative attenuation correction. This
      article provides an overview of current PET/CT scanner technology, a discussion
      of challenges faced by these systems, and pending solutions.

PMID- 15488556
TI  - Update on PET radiopharmaceuticals: life beyond fluorodeoxyglucose.
AB  - Twenty-eight years after its inception, 2-[18F]FDG- is still the most widely used
      radiopharmaceutical for PET studies, but numerous more specific radiotracers have
      been developed and applied in neuroscience and oncology. The advances in
      radiotracer chemistry, especially the nucleophilic substitution reaction, have
      played the pivotal role in synthesizing various no-carrier-added 18F-labeled
      radiotracers for PET studies of various receptor systems. This article lists some
      of the radiotracers that are available for PET studies in neuroscience and
      oncology. The prospects for developing other new radiotracers for imaging other
      organ diseases also seem to be promising.

PMID- 15488557
TI  - Quantification in PET.
AB  - Quantification provides the link between the concentrations of radioactivity
      measured in tissue and the underlying physiologic processes occurring in the
      organ. It relates the rate at which radioactivity levels in the body change over
      time to quantitative parameters such as absolute rate glucose metabolism,
      regional blood flow, or concentrations of receptors or other binding sites.
      Absolute measurement of physiologic parameters generally requires accurate
      measurement of activity concentrations in arterial blood, which provides the
      input function to the kinetic model. Although absolute quantification can be a
      difficult process, simplifications of these invasive techniques, involving
      reference tissues or normalization approaches (eg, SUV), have been applied with
      some success. Any simplified model of tracer behavior must be validated against
      the full model to test for bias and systematic errors.

PMID- 15488558
TI  - Normal variants in [18F]-fluorodeoxyglucose PET imaging.
AB  - The number of fluorodeoxyglucose PET applications is increasing. In the process
      of reading fluorodeoxyglucose-PET scans, nuclear medicine physicians encounter a
      wide variety of normal findings, which must be recognized to determine the best
      management for patients. It is important to recognize and understand normal
      variants to avoid misinterpretation of more serious pathology. This article
      reviews different patterns of physiologic fluorodeoxyglucose uptake including
      changes with age.

PMID- 15488559
TI  - Utility of fluorodeoxyglucose-PET imaging in the management of patients with
      Hodgkin's and non-Hodgkin's lymphomas.
AB  - FDG-PET imaging has a number of advantages in the management of patients with
      lymphoma. PET shows a functional metabolic status and gives quantitative
      information. In addition, PET provides whole-body images that give a
      comprehensive assessment of disease extent during the staging and followup. Based
      on the present literature, FDG-PET is at least equivalent to CT for the initial
      staging of lymphomas. The impact of new technologies of combined PET/CT and fast
      scanning CT with contrast has yet to be evaluated in the management of lymphoma
      patients, however. At this point, FDG-PET and CT must be considered as giving
      complementary staging information. FDG-PET also has high diagnostic accuracy for
      restaging lymphoma after initial treatment. FDG-PET has shown high accuracy in
      the early prediction of response to chemotherapy and in the evaluation of
      residual masses after chemotherapy or radiation therapy. Therefore, PET is likely
      to play a major role in tailoring the intensity of the treatment to the
      individual patient. A pretreatment FDG-PET study is essential for accurate
      assessment of residual masses and early monitoring of response to the treatment.
      In addition, a baseline PET scan will help detect relapse or residual disease,
      because relapse occurs most often in the region of previous disease.

PMID- 15488560
TI  - Investigation of thyroid, head, and neck cancers with PET.
AB  - PET with [(18)F]-fluorodeoxyglucose (FDG) has been accepted as a useful imaging
      modality for the diagnosis of a variety of malignancies. This article discusses
      the use of FDG-PET in the management of patients with thyroid and head or neck
      cancers.

PMID- 15488561
TI  - Fluorodeoxyglucose-PET in the management of breast cancer.
AB  - FDG-PET can be helpful in the diagnosis of primary breast cancer, especially in
      patients with dense breast tissue, significant fibrocystic changes, fibrosis
      after radiotherapy, and inconclusive results from MR imaging and other imaging
      modalities. PET has a limited role in patients with very small tumors and with
      well-differentiated and lobular types of breast cancer. In preoperative staging,
      FDG-PET has a low sensitivity for detection of regional lymph node involvement.
      Also, current PET imaging techniques can easily miss micrometastases. FDG-PET,
      however, has high positive predictive value for the axillary lymph node
      involvement, especially patient with advanced tumors. Compared with conventional
      imaging modalities, FDG-PET provides high diagnostic accuracy in detecting
      recurrent or metastatic breast carcinoma. FDG-PET seems to be highly useful for
      monitoring response to therapeutic interventions. This technique can identify
      response to therapy earlier than any other imaging method currently available.
      Obviously, identification of nonresponding patients could greatly improve patient
      management by allowing termination of ineffective and toxic therapies.

PMID- 15488562
TI  - PET imaging in assessing gastrointestinal tumors.
AB  - The clinical usefulness of FDG-PET imaging is now firmly established in various
      situations, such as the preoperative staging of esophageal cancer and recurrent
      colorectal carcinoma and the detection and staging of recurrent colorectal cancer
      when there is a clinical or biologic suspicion with inconclusive conventional
      findings. Encouraging results were obtained in the evaluation of the therapeutic
      response of various gastrointestinal malignancies, either during the treatment or
      after its completion. There is no firm consensus regarding its role in pancreatic
      cancer, either proved or suspected, but it may be valuable in selected clinical
      situations. Its role seems fairly limited in patients with hepatocellular
      carcinoma, although PET findings may have prognostic implications. Evaluation of
      cholangiocarcinoma is an emerging indication, albeit with limited data to date.
      Finally, PET/CT is very likely to enhance the role of FDG imaging further in the
      work-up of patients with gastrointestinal tumors.

PMID- 15488563
TI  - PET in the management of urologic malignancies.
AB  - FDG-PET has a limited role in diagnosis of prostate cancer mainly because of the
      low uptake of FDG in the tumor and normal excretion of FDG through urine. FDG-PET
      has shown some promise in the assessment of lymph nodes and bone metastases.
      There is a large degree of variability when FDG-PET is compared with bone
      scintigraphy. New C11-labeled radiotracers (acetate, choline, and methionine)
      have shown promising initial results but further studies are required to
      determine their role in such settings. These radiotracers provide a unique
      opportunity for dynamic, multitracer, and quantitative studies, which improve the
      sensitivity and specificity on PET in this population. Short half-lives and of C
      11, however with the limits to their use requires an on-site cyclotron. Recent
      synthesis schemes with [18F]-labeling, however, may overcome this limitation. FDG
      PET has a significant potential to assist with the diagnosis and management of
      testicular cancer. PET has been most useful in defining the presence or absence
      of disease in patients with residual masses. PET has shown promising results for
      the initial diagnosis of this cancer, but further for studies ar required to
      determine its role in the management of this malignancy. PET can be used in
      conjunction with conventional imaging techniques to diagnose retroperitoneal
      masses in patients with primary testicular cancer. FDG-PET has shown very
      encouraging results in a limited number of studies, and has also demonstrated a
      good sensitivity for initial staging. FDG-PET seems to be superior to
      conventional imaging modalities for detecting local disease and recurrence, and
      distant metastases.

PMID- 15488564
TI  - PET imaging in gynecologic malignancies.
AB  - FDG-PET has a definite role in detecting lymph node involvement and distant
      metastases. It has also shown encouraging results in assessing tumor recurrence
      and restaging, but further studies are required before FDG-PET can be
      incorporated in routine clinical practice for diagnosis of recurrence. In ovarian
      cancer, FDG-PET has high sensitivity and specificity in identifying patients with
      recurrent tumor, but lesion localization is difficult with PET. Normal FDG
      activity in the gastrointestinal tract and bladder may obscure some lesions.
      Combined PET/CT can help in localizing lesions and differentiating between
      pathologic and physiologic uptake in the pelvis and abdomen.

PMID- 15488565
TI  - The relationship between elimination rates and partition coefficients.
AB  - Rate constants for uptake and elimination of chemicals in organisms are often
      related to partition coefficients (typically the octanol-water partition
      coefficient). We show that the well-mixed one-compartment model for toxico
      kinetics implies that the elimination rate is inversely proportional to the
      square root of the partition coefficient. When chemical exchange is limited by
      diffusion in the boundary layers adjacent to the interface, two-film models are
      appropriate, which have more complex implications for the relationships between
      the exchange rates and the partition coefficient. We also show that the popular
      steady-flux approximation of the two-film model is not a conceptual
      generalization of the one-compartment model, although it shares the first-order
      kinetics. We compare the kinetics of a series of models with an increasing number
      of well-mixed compartments for exchange, such that the two-film model results for
      an infinite number of compartments. The latter model formulation in terms of
      partial differential equations, and more in particular its boundary condition at
      the interface of the two media, is believed to be new. In the steady-flux
      approximation and in the model with single well-mixed boundary layers and low
      diffusivities, the elimination rate depends hyperbolically on the partition
      coefficient. The available data for abiotic systems (SPME fibers) supports a
      hyperbolic relationship, whereas the data for aquatic biota are less
      discriminating between a hyperbolic or a square root relationship with the
      partition coefficient. The daphnia data showed less scatter than the fish data,
      possibly due to the small variance in body sizes, since elimination rates are
      inversely proportional to body length. The square root relationship fitted these
      data best.

PMID- 15488566
TI  - Adsorption of bentazon and propanil from aqueous solutions at the high area
      activated carbon-cloth.
AB  - Removal of the pesticides bentazon and propanil from single and bisolute
      solutions by adsorption at the high area activated carbon-cloth was investigated.
      Kinetics of adsorption was followed and adsorption isotherms of the two
      pesticides were determined. A special V-shaped cell with an UV cuvette attached
      to it was used for adsorption studies. With this cell it was possible to follow
      the concentration of pesticide molecule by in situ UV spectroscopy as it is
      adsorbed at the carbon-cloth. It was found that concentration of pesticides
      decreased from the same initial concentration of 4.5 x 10(-5) to 1.1 x 10(-5) for
      bentazon and to 9.5 x 10(-6) for propanil in about 2 h. The fits of experimental
      adsorption isotherm data to Langmuir and Freundlich isotherm equations were
      almost equally successful. Monolayer capacities determined from Langmuir
      isotherms of pesticides showed that bentazon has greater monolayer capacity than
      propanil. This conclusion was also confirmed through the 1/n parameter of
      Freundlich equation.

PMID- 15488568
TI  - Effect of pH and the role of organic matter in the adsorption of isoproturon on
      soils.
AB  - Equilibrium measurements were carried out with the herbicide isoproturon on
      natural adsorbents (brown forest-, chernozem-, sandy soils and quartz) in
      different buffered media (pH 5, 7, 8 phosphate buffer). Adsorption isotherms were
      fitted by a multi-step adsorption equation providing numerical information used
      in the environmental propagation models and risk assessment works. In the
      adsorption of the slightly polar isoproturon the dissolved organic matter of the
      soil and the pH play an important role. At molecular level, results are
      interpreted by taking into consideration the hydrophobic interaction and the
      formation of hydrogen bonds between the surface and the solute. The observed
      adsorption behavior indicates that the organic matter content of the soils and
      its soluble fulvic acid, alkaline soluble humic acid and insoluble humin
      fractions were considerable different. The chernozem soil containing the highest
      amount of insoluble organic fraction proved to be a very efficient adsorbent. The
      brown forest and the sandy soils exhibit rather similar adsorbent properties but
      at pH 7 the latter containing more fulvic acid adsorbs less isoproturon due to
      the enhanced solubility of the soil organic matter. In alkaline conditions the
      negatively charged solute and the surface repel each other and the hydrophobic
      interactions are also weaker than in neutral media.

PMID- 15488567
TI  - Pesticide levels in surface waters in an agricultural-forestry basin in Southern
      Chile.
AB  - Residues of five pesticides in surface water were surveyed during 2001 and 2003
      in the Traiguen river basin in Southern Chile. Simazine, hexazinone, 2,4-D,
      picloram herbicides and carbendazim fungicide were selected through a pesticide
      risk classification index. Six sampling stations along the river were set up
      based on agricultural and forestry land use. The water sampling was carried out
      before and after the pesticide application periods and in correspondence to some
      rain events. Pesticides were analyzed by HPLC with DAD detection in a
      multiresidue analysis. During 2001, in the first sampling campaign (March), the
      highest concentrations of pesticides were 3.0 microg l(-1) for simazine and
      hexazinone and 1.8 microg l(-1) for carbendazim. In the second sampling
      (September), the highest concentration were 9.7 microg l(-1) for 2,4-D, 0.3
      microg l(-1) for picloram and 0.4 microg l(-1) for carbendazim. In the last
      sampling period (December), samples indicated contamination with carbendazim
      fungicide at levels of up to 1.2 microg l(-1). In sampling carried out on May
      2003, no pesticides were detected. In October 2003, the highest concentrations of
      pesticides were 4.5 microg l(-1) for carbendazim and 2.9 microg l(-1) for 2,4-D.
      Data are discussed in function of land use and application periods of the
      products, showing a clear seasonal pattern pollution in the Traiguen river. Risk
      assessment for these pesticides was calculated by using a risk quotient (RQ =
      PNEC/PEC). For picloram the calculated RQ < was 0, which indicates that no
      adverse effects may occur due to the exposure to this herbicide in the Traiguen
      river basin. For 2,4-D, simazine, hexazinone, carbendazim RQ > 1, meaning that
      adverse effects could occur and it is necessary to reduce pesticide exposure in
      surface waters. It is recommended to continue with a pesticide monitoring program
      and the implementation of ecotoxicological testing with local and standardized
      species in order to consider the probability of effects occurrence, with less
      uncertainty. Thus, it will be more feasible to make some recommendations to
      regulatory agencies regarding the pesticide use.

PMID- 15488569
TI  - Organophosphate flame retardants and plasticizers in indoor air.
AB  - Analytical methods were developed for a broad range of organophosphate flame
      retardants and plasticizers in indoor air. Screening was performed of various
      indoor environments at 12 locations in and around Zurich, Switzerland. Method
      recoveries ranged from 62% for triphenyl phosphate to 100% for tris(2-ethylhexyl)
      phosphate. Tris(2-chloro-isopropyl) phosphate was found in the highest
      concentration (260 ng/m(3)) mainly in cars and furniture stores. Tris(2
      ethylhexyl) phosphate and triphenyl phosphate, both up to 3.4 ng/m(3), were also
      detected in quantifiable concentrations at several sites. Tris(1,3
      dichloroisopropyl) phosphate, tricresyl phosphate and tri(2-butoxyethyl)
      phosphate were below the limit of quantification in all samples. The results of
      the risk assessment indicate that the observed concentrations are below the
      predicted threshold for human health effects.

PMID- 15488570
TI  - Chromium (III) recovery from waste acid solution by ion exchange processing using
      Amberlite IR-120 resin: batch and continuous ion exchange modelling.
AB  - The use of ion exchange technology was studied to remove chromium (III) from
      acidic waste solution by Amberlite IR-120 resin. Batch and column experimental
      tests were conducted to provide data for theoretical models and verify the system
      performance of the adsorption process. Results of batch equilibrium tests
      indicated that Langmuir isotherm describes well the adsorption process, whereas
      experimental data also provide evidence that, under the present experimental
      conditions, chromium (III) adsorption by Amberlite IR-120 resin is film-diffusion
      controlled; on the other hand, the theoretical model used in the present
      investigation was found to predict reasonably well the ion exchange breakthrough
      performance.

PMID- 15488571
TI  - Impact of fermented brown rice with Aspergillus oryzae (FEBRA) intake and
      concentrations of polybrominated diphenylethers (PBDEs) in blood of humans from
      Japan.
AB  - The isotope dilution technique was applied for the analysis of new polybrominated
      diphenylethers (PBDEs) calibration standard (both labeled and non-labeled) using
      high-resolution gas chromatography-high-resolution mass spectrometry (HRGC-HRMS).
      The relative response factor (RRF) and relative standard deviation (RSD) for new
      calibration standard in Finnigan Thermo Electron (MAT-95XL) and Micromass
      (Autospec Ultima) were more or less identical with mean RRF (0.9882), RSD
      (0.0865) and CV% of (8.75). The results also revealed for DeBDE-209
      quantification; labeled DeBDE-209 is essential. Furthermore, we recommend on
      column injection technique with a thin film instead of splitless injection in
      order to reduce the thermal degradation of DeBDE-209 and formation of
      octabromodibenzofurans (OBDF). Besides, analysis of human blood (n = 156) of
      FEBRA-intake and non-FEBRA-intake individuals elucidated frequent detection of
      eighteen PBDE congeners. The average PBDE concentrations in non-FEBRA intake and
      FEBRA-intake humans were 6000-11,000 (mean: 8400) and 5400-15,000 (mean: 9900)
      respectively on pg/g fat basis. Although FEBRA-intake individuals showed slightly
      greater PBDEs, computer-normalized concentrations of TeBDE-47 corroborate FEBRA
      intake individual from four family showed reduced concentrations. The
      contamination profiles of PBDEs varied in between family, gender as well as
      geography. International comparison with predominant PBDE congener (TeBDE-47)
      prevailed lower levels in Japan when compared to Korea, Germany and USA
      nevertheless, congener specific profiles were different which is in accordance
      with different technical PBDE usage in between countries.

PMID- 15488572
TI  - The phosphine oxides Cyanex 921 and Cyanex 923 as carriers for facilitated
      transport of chromium (VI)-chloride aqueous solutions.
AB  - The behaviour of the phosphine oxides Cyanex 921 and Cyanex 923 in the
      facilitated transport of chromium (VI) from chloride solutions is described.
      Transport is studied as a function of several variables such as stirring speeds
      of the aqueous phases, membrane phase diluent, hydrochloric acid concentration in
      the source phase and chromium and carrier concentrations. The separation of
      chromium (VI) from other metals presented in the source phase as well as the
      behaviour of phosphine oxides with respect to other neutral organophosphorous
      derivatives (tri-n-butylphosphate (TBP) and dibutyl butylphosphonate (DBBP)) are
      also investigated. Moreover, by using hydrazine sulphate in the receiving phase,
      Cr(VI) is immediately reduced to the less toxic Cr(III).

PMID- 15488573
TI  - Determination of mono-, di- and trinitronaphthalenes in soil samples contaminated
      by explosives.
AB  - We investigated the extraction of eight mono-, di- and trinitronaphthalenes from
      soil samples by ultrasonic, respectively, soxhlet extraction. Sonication was the
      more convenient procedure with a usually higher repeatability than the soxhlet
      method. All extracts were analysed by high-performance liquid chromatography with
      diode array detection. These methods were used to determine the concentration of
      nitronaphthalenes in five soil samples polluted by explosives. The most abundant
      contaminants were 1,5- and 1,8-dinitronaphthalene as well as 1,3,5-, 1,3,8- and
      1,4,5-trinitronaphthalene. In all samples the sum of trinitronaphthalenes
      exceeded the sum of mono- and dinitronaphthalenes. It is recommendable to include
      these eight compounds in the analytical exploration of sites contaminated by
      explosives.

PMID- 15488574
TI  - Seasonal variability of 1-chloropyrene on atmospheric particles and
      photostability in toluene.
AB  - The occurrence of a mutagenic compound, 1-chloropyrene (Cl-Py), in extracts of
      ambient particulate matter at an urban site in Japan has been investigated.
      Samples were collected with a high-volume air sampler for 24 h periods over the
      course of 1 week in winter (February), spring (May), summer (August), and autumn
      (November) 2002. The Cl-Py levels showed seasonal variation, ranging from 2.4
      pg/m(3) (summer) to 18.9 pg/m(3) (winter). This variation would indicate that the
      lower temperatures in winter results in an increased distribution of Cl-Py from
      vapor phase to the particle phase. In addition, there is also the possibility
      that ambient Cl-Py is emitted from seasonal sources or is susceptible to
      photodegradation by sunlight, or both. The photodegradation of Cl-Py in a
      laboratory experiment was conducted to simulate the compound's fate on airborne
      particle surfaces. The degradation of Cl-Py proceeded by a first-order reaction
      with a rate constant of 0.72 h(-1). In the presence of a radical sensitizer, 9,10
      anthraquinone (AQ), the photodegradation rate of Cl-Py was elevated in comparison
      with the rate in the absence of AQ. In addition, the dechlorination of Cl-Py
      (i.e., the formation of Py) occurred in the presence of AQ.

PMID- 15488575
TI  - Metal partitioning in river sediments measured by sequential extraction and
      biomimetic approaches.
AB  - We quantified the concentrations and distributions of metals (Cd, Cr, Cu, Ni, Pb,
      and Zn) in the sediments of Tuen Mun River, Hong Kong. The potential
      bioavailability of metals was assessed with a biomimetic extraction method using
      the sipunculan gut juices. The sediments were characterized by relatively high
      concentrations of trace metals. Field collected sediments were highly anoxic and
      the ratio of simultaneously extractable metal (sigmaSEM) to acid volatile sulfide
      (AVS) was much less than one in these sediments. The majority (>67%) of Cd, Pb,
      and Zn were bound to AVS, thus their concentrations in the sediment porewater
      were low. In contrast, Ni was little bound to AVS due to its lower ratios of SEM
      Ni to total Ni concentrations. For Cu, relatively high concentrations in the
      sediment porewater was found, and total organic carbon, AVS and other resistant
      sulfide phase were the controlling factors for sedimentary Cu partitioning. Net
      metal adsorption from gut juices to anoxic sediments was observed in metal
      extraction experiments, suggesting that AVS determined the bioaccumulation and
      potential bioavailability of most metals in these sediments. Extraction of metals
      from the oxidized sediments by the gut juices was mainly attributed to metal
      redistribution from AVS to other geochemical phases. The gut juices were the most
      effective solvent or extractant than the simple electrolyte solution [I (NaNO(3))
      = 0.01 M] and the natural overlying water. Cd was more easily extracted from the
      oxidized sediments than Zn that tended to have a stronger binding affinity with
      Fe-Mn oxide, clay and organic matter. The application of partial removal
      techniques in metal extraction experiments further demonstrated the differential
      controls of various sediment geochemical phases in affecting metal
      bioavailability, with the order of TOC > Fe-Mn oxides > carbonate.

PMID- 15488576
TI  - Laboratory assessment of atrazine and fluometuron degradation in soils from a
      constructed wetland.
AB  - Constructed wetlands offer promise for removal of nonpoint source contaminants
      such as herbicides from agricultural runoff. Laboratory studies assessed the
      potential of soils to degrade and sorb atrazine and fluometuron within a recently
      constructed wetland. The surface 3 cm of soil was sampled from two cells of a
      Mississippi Delta constructed wetland; one shallow area disturbed only
      hydrologically, and the second excavated to provide greater water-holding
      capacity. The excavated area was more acidic on average (pH 4.85 versus 5.21),
      but otherwise the physical properties and general microbial enzyme activities in
      the two areas were similar. Soils were treated with 84 and 68 microg kg(-1) soil
      (14)C-ring labeled atrazine and fluometuron, respectively, and incubated under
      either saturated (88% moisture, w:w) or flooded (1cm standing water) conditions.
      Soils were sampled over 32 days and extracted for herbicide and metabolite
      analysis. Under saturated conditions, fluometuron metabolized to
      desmethylfluometuron (DMF) with a half-life equal 25-27 days. However, under
      flooded conditions, the half-life of fluometuron was more than 175 days. Atrazine
      dissipated rapidly in saturated and flooded soil with a half-life of
      approximately 23 days, but only 10% of atrazine was mineralized to CO(2). The
      overall atrazine and fluometuron dissipation rates were similar between the two
      cells, but each area had a different pattern of metabolite accumulation. The
      major route of atrazine dissipation was incorporation of atrazine residues into
      methanol-nonextractable (soil-bound) components, with minimal extractable
      metabolite accumulation. A mixed-mode extractant (potassium
      phosphate:acetonitrile) recovered greater amounts of (14)C-residues from atrazine
      treated soils, suggesting that hydrolysis of atrazine to hydroxylated metabolites
      was a major component of the bound residues. These studies indicate the potential
      for herbicide dissipation in wetland soils and a differential effect of flooding
      on the fate of these herbicides.

PMID- 15488577
TI  - Retention characteristics and balance assessment for two polycyclic musk
      fragrances (HHCB and AHTN) in a typical German sewage treatment plant.
AB  - Measurements of two polycyclic musk fragrances HHCB (galaxolide) and AHTN
      (tonalide) were measured in wastewater and sludge of a German sewage treatment
      plant. The metabolite HHCB-lactone was identified and quantified in the same
      plant. The influent concentrations were about 1900 ng/l HHCB and 580 ng/l AHTN,
      while in the sludge about 3000 ng/g HHCB and 1500 ng/g AHTN were analysed. About
      35% of both compounds passed through the plant unaltered and were discharged to
      the river. Slightly more HHCB was sorbed to the sludge than was discharged; while
      for AHTN about twice as much was sorbed to the sludge than was discharged. About
      5-10% of the HHCB was oxidised in the plant to HHCB-lactone. The dominant
      processes in the STP were sorption processes, though.

PMID- 15488578
TI  - Volatilisation of crop protection chemicals from crop and soil surfaces under
      controlled conditions--prediction of volatile losses from physico-chemical
      properties.
AB  - Volatilisation of crop protection chemicals from soil and crop surfaces is one of
      a number of processes that may contribute to their dissipation in the
      environment. Therefore, information on the potential of a chemical to volatilise
      from these surfaces is required by international and national registration
      authorities. This paper reports the results of more than 190 experiments, which
      were carried out with 80 different crop protection chemicals under controlled
      conditions (laboratory and/or greenhouse) according to the BBA guideline. Percent
      loss values observed during 24 h after application are reported for 123 soil and
      71 crop volatility studies. Generally, volatile losses from crop surfaces were
      found to be greater than from soil surfaces under comparable experimental
      conditions. It has been previously proposed that volatile losses from soil
      surfaces, from crops, and from aqueous systems can be estimated from physico
      chemical parameters. The data are therefore analysed to determine whether a
      correlation exists between volatilisation and physico-chemical parameters, such
      as vapour pressure, Henry's law constant, water/air and soil/air distribution
      coefficients. It was found that these parameters can be used to make reasonable
      predictions of volatile losses from crop and soil surfaces, which can be expected
      for crop protection chemicals under controlled conditions. Vapour pressure was
      the best predictor of losses from soil and crops. The use of the soil/air
      distribution coefficient is an alternative for predicting/estimating the
      volatility potential of a chemical from soil. Based on direct measurements, no
      noticeable volatility can be expected from compounds with a vapour pressure below
      10(-3) Pa from soil and 10(-4) Pa from crops, this is fully confirmed by indirect
      measurements. A tiered volatility testing scheme including appropriate trigger
      values is proposed.

PMID- 15488579
TI  - Prediction of ozone concentration in ambient air using multivariate methods.
AB  - Multivariate statistical methods including pattern recognition (Principal
      Component Analysis--PCA) and modeling (Multiple Linear Regression--MLR, Partial
      Least Squares--PLS, as well as Principal Component Regression--PCR) methods were
      carried out to evaluate the state of ambient air in Miskolc (second largest city
      in Hungary). Samples were taken from near the ground at a place with an extremely
      heavy traffic. Although PCA is not able to determine the significance of
      variables, it can uncover their similarities and classify the cases. PCA revealed
      that it is worth to separate day and night data because different factors
      influence the ozone concentrations during all day. Ozone concentration was
      modeled by MLR and PCR with the same efficiency if the conditions of
      meteorological parameters were not changed (i.e. morning and afternoon). Without
      night data, PCR and PLS suggest that the main process is not a photochemical but
      a chemical one.

PMID- 15488580
TI  - Butyltins in water, biofilm, animals and sediments of the west coast of India.
AB  - Biofilm, fish, oyster, mussel, clam, surface seawater, suspended particulate
      matter (SPM), and sediment samples were collected from marine and/or estuarine
      waters of the west coast of India. These samples were analysed for butyltin
      derivatives such as dibutyltin (DBT) and tributyltin (TBT). The concentrations
      DBT plus TBT varied between 2.4 and 8.3, 163 and 363 ng/l, 5 and 2853 ng/g dry wt
      in the SPM, seawater and sediment samples, respectively, of the Marmugao harbour.
      The values of DBT plus TBT ranged between 0.60 and 29, 123 and 242 ng/l and 1.4
      and 65 ng/g dry wt in SPM, water and sediment samples, respectively, collected
      from the Mandovi estuary. In the Dona Paula Bay the DBT plus TBT varied from 10
      to 89 ng/l in surface seawater, and TBT from 10 to 513 ng/g in biofilm samples.
      For the coastal sediment samples the concentration of DBT plus TBT ranged between
      36 and 133 ng/g dry wt of sediment. For the animal samples the DBT plus TBT
      ranged between 58 and 825 ng/g dry wt of the tissue. Mussel tissues contained the
      highest amount of DBT plus TBT (825 ng/g dry wt tissue), whereas highest TBT
      concentration was recorded in the oyster (732 ng/g dry wt). TBT was generally the
      most abundant butyltin compound in most of the samples suggesting fresh inputs
      and/or less degradation of TBT. A wide range of the observed butyltin
      concentrations suggests the presence of localized areas of contamination.
      Leaching of tributyltin-containing antifouling paints from the ocean going ships,
      fishing and recreational boats, barges, and the inputs of TBT from the Goa
      shipyard and dry dock facility situated in the harbour are the probable sources
      of the DBT and TBT in the samples of the west coast of India. Higher levels of
      TBT were observed in biofilm relative to that in the surrounding seawater. When
      fed on TBT contaminated biofilm of the diatom Navicula subinflata, butyltin
      concentrations in the clam Paphia malabarica increased over the period of feeding
      suggesting the importance of biofilm in the transfer of butyltins to higher group
      of organisms.

PMID- 15488581
TI  - Polycyclic aromatic hydrocarbons in the San Francisco Estuary water column:
      sources, spatial distributions, and temporal trends (1993-2001).
AB  - The composition of PAH in surface waters was examined over a range of spatial and
      temporal scales to determine distributions, trends, and possible sources. Water
      samples were collected from 1993 to 2001. PAH in organic extracts were analyzed
      by gas chromatography-mass spectrometry (GC-MS) and 25 individual target PAH
      summed to get the total PAH concentration in each water sample. The distribution
      of median total PAH concentration by estuary segments was Extreme South Bay (120
      ng l(-1)) > South Bay (49 ng l(-1)) > North Estuary (29 ng l(-1)) > Central Bay
      (12 ng l(-1)) > Delta (7 ng l(-1)). Overall, total PAH concentrations were
      significantly higher in the Extreme South Bay compared to all other segments, and
      the Central Bay and Delta were significantly lower than all other segments
      (Kruskal-Wallis, H = 157.27, df = 4, p < 0.0005). This distribution reflects the
      large urbanized and industrialized areas that border the southern portions of the
      estuary and the less populated and rural areas that surround the Delta. Temporal
      trend analysis showed a statistically significant temporal trend in total PAH
      concentration at only one of the 18 sampling stations situated throughout the
      estuary (San Jose, significant decrease, p = 0.031, r(2) = 0.386, n = 12). PAH
      isomer pair ratio analysis showed that PAH in estuary waters were derived
      primarily from combustion of fossil fuels/petroleum (possible PAH source
      contributors include coal, gasoline, kerosene, diesel, No. 2 fuel oil, and crude
      oil) and biomass (possible contributors include wood and grasses), with lesser
      amounts of PAH contributed from direct petroleum input.

PMID- 15488582
TI  - Oryzalin fate and transport in runoff water in Mediterranean vineyards.
AB  - An experimental study was conducted in a 91.4-ha Mediterranean vineyard catchment
      in southern France to characterize the fate and transport of oryzalin in runoff
      water and thus to assess the risk of contamination of surface waters. Oryzalin
      concentrations in soil were monitored on two fields, one no-till and one tilled
      from March 1998 to March 2000. Concentrations in solution and on solid phase of
      runoff water were measured at the outlets of both fields and the catchment. The
      droughts in the two summer periods reduced the dissipation of oryzalin and
      increased its field half-life up to 35 days. Consequently, oryzalin was detected
      throughout the year in runoff water, with maximum dissolved concentrations > 600
      microg l(-1) at the field scale. Oryzalin transport essentially occurred in
      solution. At the no-till field, seasonal losses were 2.29% and 1.89% of the
      applied amount in 1998 and 1999, respectively. The corresponding values at the
      tilled field were 1.56% and 0.29%, since tillage reduced total losses by reducing
      surface runoff. At the catchment scale, oryzalin concentrations were smaller than
      those at the field scale, due to dilution effects and staggering of application.
      Large part of the overland flow from the fields reinfiltrated in the ditches
      before reaching the outlet of the catchment. As a result, seasonal oryzalin
      losses were <0.2% of the applied amount.

PMID- 15488583
TI  - Characterising sources and sinks of rural VOC in eastern France.
AB  - Fifty non-methane hydrocarbons (NMHC) and seventeen carbonyl compounds were
      measured at a French rural site from 1997 to 2001, as part of the EMEP programme.
      Data handling was based on an original source-receptor approach. First, the
      examination of the levels and trends was completed by the comparison of the
      seasonal distribution of rural and urban VOC/acetylene ambient ratios. This
      analysis has shown that most of the compounds derived from mixing and
      photochemical transformation of mid-range transported urban pollutants from the
      downwind urban area. Then, identified sources and sinks were temporally
      apportioned. Urban air masses mixing explains, at least, 80% of the wintertime
      levels of anthropogenic NMHC and isoprene. In summer, photochemistry dominates
      the day-to-day distribution of anthropogenic NMHC whilst summertime isoprene is
      also controlled by in-situ biogenic emissions. Then, the results of C(1)-C(3)
      carbonyls were discussed with respect to their direct biogenic and anthropogenic
      emissions and photochemical production through the [carbonyl/auto-exhaust
      tracers] emission ratio. Diluted vehicle exhaust emissions mainly contribute to
      the total content of lower aldehydes in winter while other processes control
      lower ketones. Secondary production is predominant in summer with at least a 50%
      high intensity. Its dependence upon temperature and radiation is also
      demonstrated. Finally, the importance of the primary and secondary biogenic
      production of acetone and formaldehyde is assessed. In particular, biogenic
      contribution would explain 37 +/- 25% of acetone levels in summer.

PMID- 15488584
TI  - Metabolism of aromatic hydrocarbons by the filamentous fungus Cyclothyrium sp.
AB  - The metabolism of biphenyl, naphthalene, anthracene, phenanthrene, pyrene and
      benzo[a]pyrene by Cyclothyrium sp. CBS 109850, a coelomycete isolated for the
      first time in Brazil from industrially polluted estuarine sediment, was studied.
      The metabolites were extracted and separated by high performance liquid
      chromatography (HPLC) and characterized by UV spectral analyses and mass, and
      proton nuclear magnetic resonance ((1)H NMR) spectrometry. Cyclothyrium sp.
      transformed biphenyl to 4-hydroxybiphenyl and anthracene to anthracene trans-1,2
      dihydrodiol. This isolate metabolized 90% of [9-(14)C]phenanthrene, producing
      phenanthrene trans-9,10-dihydrodiol as a major metabolite, phenanthrene trans-3,4
      dihydrodiol, 1-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene,
      and a novel metabolite, 2-hydroxy-7-methoxyphenanthrene. Circular dichroism
      spectra analyses indicated that the major enantiomers of phenanthrene trans-9, 10
      dihydrodiol, phenanthrene trans-3,4-dihydrodiol and pyrene trans-4,5-dihydrodiol,
      a pyrene metabolite produced previously by Cyclothyrium sp. CBS 109850, were
      predominantly in the (R,R) configuration, revealing a high stereoselectivity for
      initial monooxygenation and enzymatic hydration of phenanthrene and pyrene by
      Cyclothyrium sp. CBS109850. The results also show a high regioselectivity since
      the K-regions of phenanthrene and pyrene were the major sites of metabolism.

PMID- 15488585
TI  - Physicochemical forms of technetium in surface water covering paddy and upland
      fields.
AB  - The behavior of an element in the environment depends on its physicochemical
      form. Basic data for the behavior of technetium in an agricultural environment
      were obtained by determining the physicochemical forms of Tc in 28 surface water
      samples from paddy and upland fields. Most of the (95m)Tc was present as TcO(4)(
      ) in the samples. The relative amount of this chemical form was 72% on average. A
      significant amount of insoluble Tc (particles more than 0.2 microm in size),
      however, was found in some samples. The maximum amount of the insoluble Tc was
      91%. Other forms were found in insignificant amounts. The amount of insoluble Tc
      was relatively high in paddy soil samples. Paddy soils, gley soils and gray
      lowland soils were particularly effective in the insolubilization of Tc. Among
      the soil characteristics studied, cation exchange capacity, anion exchange
      capacity, and active aluminum showed significant correlations with the relative
      amount of insoluble Tc. When microorganisms were eliminated from the surface
      water samples before the addition of (95m)TcO(4)(-), little insoluble Tc was
      found, suggesting that microorganisms cause the physicochemical transformation.
      These results showed that the physicochemical form of Tc changes from TcO(4)(-)
      to insoluble forms in surface water covering paddy fields. The insoluble forms
      would restrict the mobility of Tc in paddy fields.

PMID- 15488586
TI  - Effect of halides in the electrochemical treatment of distillery effluent.
AB  - Electrochemical treatment can solve the problems arising due to effluents and
      offer an effective alternative to the existing methods. An undivided static
      electrolyser was charged with distillery effluent and the organics were oxidized
      electrochemically. Anodized graphite plate anodes and graphite cathodes were used
      for the treatment of distillery effluent. The effect of pH and current density on
      the treatment was studied. Sodium fluoride, sodium chloride and sodium bromide
      were chosen as electrolyte and their influence was found out. Complete
      decolorization has been observed in all cases. A maximum of 93.5% of biological
      oxygen demand reduction, 85.2% of chemical oxygen demand reduction and 98.0%
      absorbance reduction were obtained in the presence of sodium chloride as
      supporting electrolyte. Probable mechanism was also proposed for the oxidation of
      organics present in the effluent.

PMID- 15488587
TI  - Determination of diazepam in aquatic samples by capillary liquid chromatography
      electrospray tandem mass spectrometry.
AB  - In recent years growing attention has been paid toward the discharge, presence
      and potential adverse effects of pharmaceuticals in the environment. Using
      different existing analytical methods several studies have already identified a
      variety of drugs in waste-, surface- and drinking water. The monitoring of
      surface waters for drugs is of great importance because drugs are designed to be
      biological very active substances. A capillary LC/ES-MS-MS method has been
      developed that enables the sensitive and specific detection of diazepam in water
      samples up to 0.1 ng/ml (LOD). It requires neither multiple extraction steps, nor
      the use of large volumes of organic solvent. Applying this assay we have detected
      diazepam in 'in/effluent samples' collected in Belgium and demonstrated the
      applicability for water analysis without off-line pre-concentration of the
      analyte.

PMID- 15488588
TI  - Biacore biosensor immunoassay for 4-nonylphenols: assay optimization and
      applicability for shellfish analysis.
AB  - A rapid Biacore biosensor immunoassay of 4-nonylphenols was developed. Two types
      of antibodies were used in the study: polyclonal antibodies with high cross
      reactivity towards technical 4-nonylphenol and a monoclonal antibody very
      specific to 4-n-nonylphenol. 9-(p-Hydroxyphenyl)nonanoic acid was immobilized
      onto surface of a sensor chip. The best assay sensitivity was achieved using a
      flow rate of 50 microl min(-1) and injection time of 2 min. For the assay
      incorporating monoclonal antibodies a limit of detection 2 ng ml(-1) for 4-n
      nonylphenol was achieved. With polyclonal antibodies one order lower sensitivity
      was observed for 4-nonylphenols. High background level of calibration curve for
      technical 4-nonylphenol was decreased by using IgG fraction of polyclonal
      antibodies in combination with lower amount of immobilised 9-(p
      hydroxyphenyl)nonanoic acid. Sensitivity of the assay was improved by using a
      chip with a new derivative on a surface-N-aminobutyl [2-(4
      hydroxyphenyl)ethylamine] (limit of detection--5 ng ml(-1)). Applicability of the
      developed assays to ecological monitoring was checked in experiments using
      shellfish samples. 4-n-Nonylphenol from spiked samples was extracted into hexane
      followed by clean-up on NH2 SPE columns. Calibration curves generated for
      cockles, mussels and oyster samples were identical (limit of detection about 10
      ng g(-1)) whereas for scallop samples a slight decrease (about 5-10%) of absolute
      response was observed. In the assay using the monoclonal antibody specific to 4-n
      nonylphenol 31 shellfish samples were found to be negative. Results obtained with
      polyclonal antibodies indicated that two scallop samples contained a quantity of
      4-nonylphenols. The developed biosensor assay could be applied for shellfish
      analysis as a preliminary screening method.

PMID- 15488589
TI  - Considerations about the enantioselective transformation of polycyclic musks in
      wastewater, treated wastewater and sewage sludge and analysis of their fate in a
      sequencing batch reactor plant.
AB  - The present work consists of two distinct parts: in the first part
      enantioselective GC was used to separate the different
      enantiomeric/diastereomeric polycyclic musks, PCMs (HHCB, AHTN, AHDI, ATII and
      DPMI) including the main transformation product of HHCB, HHCB-lactone, in
      wastewater and sewage sludge. After optimization all PCMs were resolved on a
      cyclodextrin containing Rt-BDEXcst capillary GC column. Enantiomeric ratios of
      PCMs in a technical mixture were determined and compared to those obtained from
      enantioselective separation of wastewater and sewage sludge samples. In general,
      enantiomeric ratios were similar for most materials in influent, effluent and
      stabilized sewage sludge. However, the ratios for HHCB, AHDI and particularly
      ATII suggest some stereospecific removal of these compounds. In the second part,
      a field study was conducted on a wastewater treatment plant comprising a
      sequencing batch reactor. Concentrations of HHCB, AHTN, ADBI, AHDI, ATII, DPMI
      and HHCB-lactone were determined by non-enantioselective GC in daily samples of
      influent, effluent and activated sludge during one week. Mean concentrations in
      influent were 6900 and 1520 ng/l for HHCB and AHTN, respectively. The other PCMs
      exhibited contents 200 ng/l. Mean percent removal was between 61% (AHDI) and 87%
      (HHCB) resulting in mean effluent concentrations below 860 ng/l. HHCB-lactone
      concentration increased during wastewater treatment with a mean in the influent
      of 430 ng/l and in the effluent of 900 ng/l, respectively, indicating a
      degradation of HHCB.

PMID- 15488590
TI  - Aquatic macrophytes potential for the simultaneous removal of heavy metals
      (Buenos Aires, Argentina).
AB  - Heavy metal removal from water has been approached by using different
      technologies. Phytotechnologies, with an increasing development during the last
      two decades, involve using plants for metal removal. Three autochthonous floating
      macrophytes, common in pampean shallow lakes (Argentina), Pista stratiotes,
      Spirodela intermedia and Lemna minor were used in laboratory experiences for the
      simultaneously removal of several heavy metals (Fe, Cu, Zn, Mn, Cr and Pb)
      resulting from anthropogenic activity, in order to simulate a naturally polluted
      environment. The experiences were performed for different concentrations of
      metals along 15 days. High metal removal percentages were obtained for the 3
      species and metals. L. minor did not survive the conditions of the experiment.
      High correlation between the final water and the macrophytes metal concentration
      was obtained, deviations were due to PbCrO(4) precipitation. The rate of metal
      uptake was dependent on the metal concentration for the 3 species studied.

PMID- 15488591
TI  - Effects of heavy metals and nitroaromatic compounds on horseradish glutathione S
      transferase and peroxidase.
AB  - Glutathione S-transferase (GST) and peroxidase (POX) activities have a direct
      relation to the effect of stress on plant metabolism. Changes in the activities
      of the enzymes were therefore studied. Horseradish hairy roots were treated by
      selected bivalent ions of heavy metals (HMs) and nitroaromatic compounds (NACs).
      We have shown differences in GST activity when assayed with substrates 1-chloro
      2,4-dinitrobenzene (CDNB) and 1,2-dichloro-4-nitrobenzene (DCNB). The conjugation
      of DCNB catalysed by GST was inhibited in all roots treated with HMs as compared
      to non-treated roots, whereas NACs caused induction of the activity in dependence
      on the exposition time and concentration of compounds. The conjugation of CDNB by
      GST was not affected to the same extent. The increase of GST activity was
      determined in cultures treated by nickel (0.1 mM) and diaminonitrotoluenes
      (DANTs, 0.1 mM) for 6 h, whereas the roots treated by 2,4,6-trinitrotoluene
      (TNT), 4-amino-2,6-dinitrotoluene (ADNT) and dinitrotoluene (DNT, 1.0 mM) needed
      27 h treatment to induce the activity. The POX activity of cultures treated by
      HMs was inhibited to 17-35% in comparison to non-treated cultures. The POX
      activity of roots treated by TNT (0.1 and 1.0 mM) for 6 and 27 h and by ADNT (0.1
      and 1.0 mM) for 6 h was inhibited. A partial increase of POX activity was
      measured in roots treated by all NACs for 27 h. The content of oxidized
      glutathione (GSSG) and reduced glutathione (GSH) in the roots differed
      significantly. It was followed as a symptom of the stress reaction of the plant
      metabolism to the effect of NACs and HMs.

PMID- 15488592
TI  - Nitrification in natural waters with high suspended-solid content--a study for
      the Yellow River.
AB  - In this research, the mechanism regarding the effects of suspended solids on
      nitrification in freshwater systems with high solid contents was examined.
      Experimental studies were conducted for natural water of the Yellow River under
      laboratory conditions. Nitrification kinetics was investigated in water systems
      with various levels of suspended-solid contents. The associated mechanisms were
      analyzed through investigation of the adsorption-desorption of ammonium nitrogen,
      the process of bacteria growth, and the feature of nitrification kinetics. The
      results indicated that the presence of suspended solids could accelerate the
      nitrification process. The nitrification rate would increase non-linearly with
      the increase of suspended-solid content. When the initial concentration of
      ammonia nitrogen was 12.70 mg/l in the water system, the ratios of half-time
      duration for nitrification would be 1.88:1.23:1 under suspended-solid contents of
      0, 1.84 and 5.00 g/l, respectively. When the initial concentration of ammonia
      nitrogen was around 1.0 mg/l in the water system, the nitrification rates in
      systems with suspended-solid contents of 1.81 and 3.42 g/l would then be
      approximately 9 and 12 times that without suspended solids, respectively. The
      populations of nitrifying bacteria would rise with increasing suspended-solid
      content. The existence of suspended solids would increase the contact chances
      between bacteria and nitrogen, resulting in accelerated nitrification processes;
      this was manifested by the increased K(4) (tau(max)/K(S)) along with the raised
      suspended-solid contents while fitting nitrification kinetics with the growth
      based logistic model. Since the amount of ammonium nitrogen adsorbed on suspended
      solid surface was non-linearly proportional to the suspended-solid content, the
      nitrification rate was also non-linearly proportional to the suspended-solid
      content.

PMID- 15488593
TI  - Accumulation of sulfur and heavy metals in soil and tree leaves sampled from the
      surroundings of Tuncbilek Thermal Power Plant.
AB  - In this study, the quantities of sulfur and heavy metals, resulting from the
      Tuncbilek Thermal Power Plant (TPP) in Turkey, have been assessed in tree leaves
      and soil samples within a 10 km radius of the plant. Leaves of Salix alba L.,
      Populus tremula L., Robinia pseudoacacia L., Quercus infectoria L., Pinus nigra
      Arn. ssp. pallasiana (Lamb) Holmboe. trees have been used with the aim of
      determining how far the gas and particles emitted from the TPP are carried, and
      for assessment of environmental impact. The results obtained from locations
      chosen at various distances to the TPP, indicate that the contaminating agents
      are very dense and effective; particularly in the prevailing wind direction and
      within 10 km of the plant. They gradually lose their density and effect beyond
      this distance. The sulfur and heavy metal analyses made in soils taken from these
      locations indicate a similarity with the data obtained from the leaves.

PMID- 15488594
TI  - Inositol 1,4,5-trisphosphate receptor subtypes are differentially distributed
      between smooth muscle and endothelial layers of rat arteries.
AB  - In blood vessels, the ability to control vascular tone depends on extracellular
      calcium entry and the release of calcium from inositol 1,4,5-trisphosphate
      receptor (IP3R)-gated stores located in both the endothelial and smooth muscle
      cells of the vascular wall. Therefore, we examined mRNA expression and protein
      distribution of IP3R subtypes in intact aorta, basilar and mesenteric arteries of
      the rat. IP3R1 mRNA was predominantly expressed in all three arteries.
      Immunohistochemistry showed that IP3R1 was present in both the muscle and
      endothelial cell layers, while IP3R2 and IP3R3 were largely restricted to the
      endothelium. Weak expression of IP3R2 was observed in the smooth muscle of the
      basilar artery. Co-localisation studies of IP3R subtypes with known cellular
      elements showed no association of any of the three subtypes with the endothelial
      cell plasma membrane, but a close association between the subtypes and actin
      filaments was observed in all cell layers. IP3R2 was found to be present near the
      endothelial cell nucleus. We are the first to demonstrate differential IP3R
      subtype distribution between the cell layers of the intact vascular wall and
      hypothesise that this may underlie the diversity of IP3R-dependent responses,
      such as vasoconstriction, vasodilation and vasomotion, displayed by arteries.

PMID- 15488595
TI  - The blocking of capacitative calcium entry by 2-aminoethyl diphenylborate (2-APB)
      and carboxyamidotriazole (CAI) inhibits proliferation in Hep G2 and Huh-7 human
      hepatoma cells.
AB  - Calcium entry is a component of the processes regulating the proliferative
      phenotype of some types of cancer. In non-excitable cells, capacitative calcium
      entry (CCE) and non-capacitative calcium entry (NCCE) are thought to be the main
      pathways of Ca2+ influx into cells. Thus, blocking calcium entry may prevent
      normal and pathological cell proliferation and there is evidence to suggest that
      molecules blocking calcium entry also have antiproliferative properties.
      Carboxyamidotriazole (CAI), a novel inhibitor of the non-voltage-dependent
      calcium entry has been shown to have such properties in model systems in vitro
      and in vivo. We used Hep G2 and Huh-7 human hepatoma cells to investigate the
      effects of calcium entry blockers on cell proliferation. CAI (10 microM) and 2
      APB (20 microM) completely blocked CCE in thapsigargin-treated Huh-7, and CAI and
      2-APB inhibited cell proliferation with IC50 of 4.5 and 43 microM, respectively.
      The plateau phase of the [Ca2+]i increases triggered by 10% FCS were abolished in
      the absence of external Ca2+ and in the presence of CAI or 2-APB. We, therefore,
      suggest that CCE is the main pathway involved in regulation of the processes
      leading to cell proliferation.

PMID- 15488596
TI  - Pertussis toxin-sensitive pathway inhibits glucose-stimulated Ca2+ signals of rat
      islet beta-cells by affecting L-type Ca2+ channels and voltage-dependent K+
      channels.
AB  - A role of pertussis toxin (PTX)-sensitive pathway in regulation of glucose
      stimulated Ca2+ signaling in rat islet beta-cells was investigated by using
      clonidine as a selective agonist to alpha2-adrenoceptors which link to the
      pathway. An elevation of extracellular glucose concentration from 5.5 to 22.2 mM
      (glucose stimulation) increased the levels of [Ca2+]i of beta-cells, and
      clonidine reversibly reduced the elevated levels of [Ca2+]i. This clonidine
      effect was antagonized by yohimbine, and abolished in beta-cells pre-treated with
      PTX. Clonidine showed little effect on membrane currents including those through
      ATP-sensitive K+ channels induced by voltage ramps from -90 to -50 mV. Clonidine
      showed little effect on the magnitude of whole-cell currents through L-type Ca2+
      channels (ICa(L)), but increased the inactivation process of the currents.
      Clonidine increased the magnitude of the voltage-dependent K+ currents (IVK).
      These clonidine effects on ICa(L) and IVK were abolished in beta-cells treated
      with PTX or GDP-betaS. These results suggest that the PTX-sensitive pathway
      increases IVK activity and decreases ICa(L) activity of islet beta-cells,
      resulting in a decrease in the levels of [Ca2+]i elevated by depolarization
      induced Ca2+ entry. This mechanism seems responsible at least in part for well
      known inhibitory action of PTX-sensitive pathway on glucose-stimulated insulin
      secretion from islet beta-cells.

PMID- 15488597
TI  - Calcium release from the Golgi apparatus and the endoplasmic reticulum in HeLa
      cells stably expressing targeted aequorin to these compartments.
AB  - Extracellular agonists mobilize Ca2+ from SERCA-comprising intracellular Ca2+
      stores located in both the Golgi apparatus and the endoplasmic reticulum. Ca2+
      release from both these compartments was studied in HeLa cells stably expressing
      the luminescent Ca2+ indicator aequorin specifically targeted to these
      compartments. Changes in lumenal [Ca2+] as detected by the aequorin measurements
      were correlated with parallel changes in total Ca2+ content of the stores. The
      latencies and initial rates of Ca2+ release from the Golgi apparatus and the
      endoplasmic reticulum were quite similar. However, maximal Ca2+ release measured
      with Golgi-targeted aequorin terminated faster than that from the endoplasmic
      reticulum. The rate and extent of Ca2+ depletion from both compartments
      correlated well with the peak amplitude of the cytosolic [Ca2+] rise. Time-course
      experiments further revealed that the peak of the cytosolic Ca2+ response
      occurred before the lumenal [Ca2+] reached its lowest level. We conclude that
      both the Golgi apparatus and the endoplasmic reticulum contribute to the rise in
      cytosolic [Ca2+] upon agonist stimulation, but the kinetics of the Ca2+ release
      are different.

PMID- 15488598
TI  - The role of voltage gated T-type Ca2+ channel isoforms in mediating
      "capacitative" Ca2+ entry in cancer cells.
AB  - The mechanism by which Ca2+ enters electrically non-excitable cells is unclear.
      The sensitivity of the Ca2+ entry pathway in electrically non-excitable cells to
      inhibition by extracellular Ni2+ was used to direct the synthesis of a library of
      simple, novel compounds. These novel compounds inhibit Ca2+ entry into and,
      consequently, proliferation of several cancer cell lines. They showed
      stereoselective inhibition of proliferation and Ca2+ influx with identical
      stereoselective inhibition of heterologously expressed Cav3.2 isoform of T-type
      Ca2+ channels. Proliferation of human embryonic kidney (HEK)293 cells transfected
      with the Cav3.2 Ca2+ channel was also blocked. Cancer cell lines sensitive to our
      compounds express message for the Cav3.2 T-type Ca2+ channel isoform, its
      delta25B splice variant, or both, while a cell line resistant to our compounds
      does not. These observations raise the possibility that clinically useful drugs
      can be designed based upon the ability to block these Ca2+ channels.

PMID- 15488599
TI  - Mitochondrial localization as a determinant of capacitative Ca2+ entry in HeLa
      cells.
AB  - Whether different subsets of mitochondria play distinct roles in shaping
      intracellular Ca2+ signals is presently unresolved. Here, we determine the role
      of mitochondria located beneath the plasma membrane in controlling (a) Ca2+
      release from the endoplasmic reticulum (ER) and (b) capacitative Ca2+ entry. By
      over-expression of the dynactin subunit dynamitin, and consequent inhibition of
      the fission factor, dynamin-related protein (Drp-1), mitochondria were
      relocalised from the plasma membrane towards the nuclear periphery in HeLa cells.
      The impact of these changes on free calcium concentration in the cytosol
      ([Ca2+]c), mitochondria ([Ca2+]m) and ER ([Ca2+]ER) was then monitored with
      specifically-targeted aequorins. Whilst dynamitin over-expression increased the
      number of close contacts between the ER and mitochondria by >2.5-fold, assessed
      using organelle-targeted GFP variants, histamine-induced changes in organellar
      [Ca2+] were unaffected. By contrast, Ca2+ influx elicited significantly smaller
      increases in [Ca2+]c and [Ca2+]m in dynamitin-expressing than in control cells.
      These data suggest that the strategic localisation of a subset of mitochondria
      beneath the plasma membrane is required for normal Ca2+ influx, but that the
      transfer of Ca2+ ions between the ER and mitochondria is relatively insensitive
      to gross changes in the spatial relationship between these two organelles.

PMID- 15488600
TI  - Novel fluo-4 analogs for fluorescent calcium measurements.
AB  - We report new fluorescent calcium indicators based on fluo-4. Attachment of a
      carboxamide or methylenecarboxamide moiety to the BAPTA chelator portion of fluo
      4 allowed for the attachment of dextrans, protein-reactive moieties, and biotin.
      In particular, a high affinity fluo-4 dextran conjugate was prepared and shown to
      be functional in brain slices. All new probes were characterized
      spectroscopically and exhibited large fluorescence increases upon calcium
      binding. The biotinylated version of fluo-4 formed a persistent streptavidin
      complex which still responded to increasing calcium concentrations with a large
      fluorescence increase.

PMID- 15488601
TI  - NAADP triggers the fertilization potential in starfish oocytes.
AB  - In invertebrates oocytes or eggs, the fertilization or activation potential
      establishes the fast electrical block to polyspermy and, in some species,
      provides the Ca2+ influx which contributes to the following intracellular Ca2+
      wave. In echinoderms, the molecule triggering the activation potential is still
      unknown. The aim of this study was to assess whether nicotinic acid-adenine
      dinucleotide phosphate (NAADP) elicited the fertilization potential in starfish
      oocytes. The changes in membrane potential induced by the sperm were measured in
      oocytes held at a low resting potential, so that the Ca2+-action potential was
      inactivated and only the initial slower depolarization caused by the sperm could
      be studied. Decreasing extracellular Na+ concentration did not prevent the onset
      of the fertilization potential, while removal of external Ca2+ abolished it. The
      pre-incubation with SK&F 96365 and verapamil and the pre-injection of BAPTA
      inhibited the fertilization potential, while the injection of heparin only
      reduced its duration. The biophysical and pharmacological properties of the sperm
      elicited depolarization were similar to those displayed by the NAADP-activated
      Ca2+-mediated current recently described in starfish oocytes. Indeed, the
      desensitization of NAADP-receptors prevented the onset of the fertilization
      potential. Taken together, these data suggest that NAADP could trigger the
      fertilization potential in starfish oocytes.

PMID- 15488602
TI  - Differential functional properties of Ca2+ stores in pulmonary arterial conduit
      and resistance myocytes.
AB  - In smooth muscle cells, oscillations of intracellular Ca2+ concentration
      ([Ca2+]i) are controlled by inositol 1,4,5-trisphosphate (InsP3) and ryanodine
      (Ry) receptors on the sarcoplasmic reticulum (SR). Here we show that these Ca2+
      oscillations are regulated differentially by InsP3 and Ry receptors in cells
      dispersed from the main trunk of the pulmonary artery (conduit myocytes) or from
      tertiary and quaternary arterial branches (resistance myocytes). Ry receptor
      antagonists inhibit either spontaneous or ATP-induced Ca2+ oscillations in
      resistance myocytes but they do not affect the oscillations in most conduit
      myocytes. In contrast, agents that inhibit InsP3 production or activation of
      InsP3 receptors do not alter the oscillations is resistance myocytes but block
      them in conduit myocytes. We have also examined the degree of overlap of Ry- and
      InsP3-sensitive stores in myocytes along the pulmonary arterial tree. In conduit
      myocytes, depletion of Ry-sensitive stores with repeated application of caffeine
      in the presence of Ry or in Ca2+ free solutions did not prevent the ATP-induced
      Ca2+ release from InsP3-dependent stores. However, responsiveness to ATP was
      completely abolished in resistance myocytes subjected to the same experimental
      protocol. Thus, InsP3- and Ry-dependent stores appear to be separated in conduit
      myocytes but joined in resistance myocytes. These data demonstrate for the first
      time differential properties of intracellular Ca2+ stores and receptors in
      myocytes distributed along the pulmonary arterial tree and help to explain the
      distinct functional responses of large and small pulmonary vessels to vasoactive
      agents.

PMID- 15488604
TI  - Mannose binding lectin (MBL) and HIV.
AB  - The envelope protein (gp120/gp41) of HIV-1 is highly glycosylated with about half
      of the molecular mass of gp120 consisting of N-linked carbohydrates. While
      glycosylation of HIV gp120/gp41 provides a formidable barrier for development of
      strong antibody responses to the virus, it also provides a potential site of
      attack by the innate immune system through the C-type lectin mannose binding
      lectin (MBL) (also called mannan binding lectin or mannan binding protein). A
      number of studies have clearly shown that MBL binds to HIV. Binding of MBL to HIV
      is dependent on the high-mannose glycans on gp120 while host cell glycans
      incorporated into virions do not contribute substantially to this interaction. It
      is notable that MBL, due to its specificity for the types of glycans that are
      abundant on gp120, has been shown to interact with all tested HIV strains. While
      direct neutralization of HIV produced in T cell lines by MBL has been reported,
      neutralization is relatively low for HIV primary isolates. However, drugs that
      alter processing of carbohydrates enhance neutralization of HIV primary isolates
      by MBL. Complement activation on gp120 and opsonization of HIV due to MBL binding
      have also been observed but these immune mechanisms have not been studied in
      detail. MBL has also been shown to block the interaction between HIV and DC-SIGN.
      Clinical studies show that levels of MBL, an acute-phase protein, increase during
      HIV disease. The effects of MBL on HIV disease progression and transmission are
      equivocal with some studies showing positive effects and other showing no effect
      or negative effects. Because of apparently universal reactivity with HIV strains,
      MBL clearly represents an important mechanism for recognition of HIV by the
      immune system. However, further studies are needed to define the in vivo
      contribution of MBL to clearance and destruction of HIV, the reasons for low
      neutralization by MBL and ways that MBL anti-viral effects can be augmented.

PMID- 15488605
TI  - Complement-opsonized HIV: the free rider on its way to infection.
AB  - The complement system (C) is one of the main humoral components of innate
      immunity. Three major tasks of C against invading pathogens are: (i) lysis of
      pathogens by the formation of the membrane attack complex (MAC); (ii)
      opsonization of pathogens with complement fragments to favor phagocytosis; and
      (iii) attraction of inflammatory cells by chemotaxis. Like other particles, HIV
      activates C and becomes opsonized. To escape complement-mediated lysis, HIV has
      adopted various properties, which include the acquisition of HIV-associated
      molecules (HAMs) belonging to the family of complement regulators, such as CD46,
      CD55, CD59, and the interaction with humoral regulatory factors like factor H
      (fH). Opsonized virus may bind to complement receptor positive cells to infect
      them more efficiently or to remain bound on the surface of such cells. In the
      latter case HIV can be transmitted to cells susceptible for infection. This
      review discusses several aspects of C-HIV interactions and provides a model for
      the dynamics of this process.

PMID- 15488606
TI  - Role of cytokines and chemokines in the regulation of innate immunity and HIV
      infection.
AB  - The earliest defense against microbial infection is represented by the responses
      of the innate (or natural) immune system, that also profoundly regulates the
      adaptive (or acquired) T- and B-cell immune responses. Activation of the innate
      immune system is primed by microbial invasion in response to conserved structures
      present in large groups of microorganisms (LPS, peptidoglycan, double-stranded
      RNA), and is finely tuned by different cell types (including dendritic cells,
      macrophages, natural killer cells, natural killer T cells, and gammadelta T
      cells). In addition, several soluble factors (complement components, defensins,
      mannose-binding lectins, interferons, cytokines and chemokines) can play a major
      role in the regulation of both the innate and adaptive immunity. In this review,
      we will briefly overview the regulation of some cellular subsets of the innate
      immune system particularly involved in human immunodeficiency virus (HIV)
      infection and then focus our attention on those cytokines and chemokines whose
      levels of expression are more profoundly affected by HIV infection and that,
      conversely, can modulate virus infection and replication.

PMID- 15488607
TI  - Neopterin in HIV-1 infection.
AB  - Neopterin is well established as a reliable marker in HIV-1 infection. Neopterin
      concentrations measured in urine or serum indicate sensitively the course and
      progression of the disease as well as efficacy of anti-retroviral therapy. The
      main trigger for neopterin production is Th1-type cytokine interferon-gamma.
      During acute HIV-1 infection, enhanced formation of neopterin occurs already at a
      very early time point, before antibody seroconversion takes place. After this
      stage, neopterin concentrations in serum and urine closely correlate with virus
      load in the circulation of HIV-1-infected patients. Data provide evidence for an
      important role of immune activation and Th1-type cytokine interferon-gamma in the
      pathogenesis of HIV-1 infection. This review subsumes the importance of neopterin
      as a marker in HIV-1 infection. Further evidence is increasing, that neopterin
      derivatives might modulate immune response by interfering with the cellular redox
      balance, activating redox-sensitive transcription factors, or inducing apoptosis
      in specific cell types. The possible impact of neopterin derivatives and of other
      biochemical pathways induced by interferon-gamma such as indoleamine 2,3
      dioxygenase in chronic diseases like HIV-1 infection is discussed.

PMID- 15488608
TI  - Macrophages and HIV-1: dangerous liaisons.
AB  - HIV-1, like the other lentiviruses, has evolved the ability to infect nondividing
      cells including macrophages. HIV-1 replication in monocytes/macrophages entails
      peculiar features and differs in many respects from that in CD4 T lymphocytes.
      HIV-1 exhibits different tropism for CD4 T cells and macrophages. The virus can
      enter macrophages via several routes. Mitosis is not required for nuclear import
      of viral DNA or for its integration into the host cell genome. Specific cellular
      factors are required for HIV-1 transcription in macrophages. The assembly and
      budding of viral particles in macrophages take place in late endosomal
      compartments. Viral particles can use the exosome pathway to exit cells. Given
      their functions in host defence against pathogens and the regulation of the
      immune response plus their permissivity to HIV-1 infection, monocytes/macrophages
      exert a dual role in HIV infection. They contribute to the establishment and
      persistence of HIV-1 infection, and may activate surrounding T cells favouring
      their infection. Furthermore, monocytes/macrophages act as a Trojan horse to
      transmit HIV-1 to the central nervous system. They also exhibit antiviral
      activity and express many molecules that inhibit HIV-1 replication. Activated
      microglia and macrophages may also exert a neurotrophic and neuroprotective
      effect on infected brain regulating glutamate metabolism or by secretion of
      neurotrophins. This review will discuss specific aspects of viral replication in
      monocytes/macrophages and the role of their interactions with the cellular
      environment in HIV-1 infection swinging between protection and pathogenesis.

PMID- 15488609
TI  - HIV-infection of the central nervous system: the tightrope walk of innate
      immunity.
AB  - Infection of the central nervous system (CNS) by HIV is a frequent and sometimes
      very early event in the course of HIV pathogenesis. Possible consequences are
      diverse symptoms of neurological dysfunction, but also the establishment of a
      lifelong latent viral reservoir in the brain. Whereas in the periphery innate and
      adaptive immunity are equal partners, the blood-brain barrier (BBB) with its
      restricted access of peripheral immune effectors shifts this balance in favour of
      the local innate immunity. Four main elements of cerebral innate immunity are
      discussed in the present article, including two cell types with immunological
      functions and two soluble immune systems: (1) the stimulation of microglial cells
      as the predominant brain-resident immune cell and the main local reservoir for
      the virus; (2) the reaction of astrocytes in response to viral infection; (3) the
      activation of the local complement system as important soluble immune cascade;
      and (4) the role of chemokines and cytokines which help to conduct and cross-link
      the interplay between the different immune elements. These components of the
      cerebral innate immunity do not act separately from each other but form a
      functional immunity network. A dual role of these components with both harmful
      and protective effects further enhances the complexity of the mutual
      interactions.

PMID- 15488610
TI  - Mechanisms promoting dendritic cell-mediated transmission of HIV.
AB  - Dendritic cells (DC) survey epithelial or mucosal surfaces for antigens, take
      them up via their endocytic or phagocytic receptors, process the captured
      antigens and migrate to the lymphatic tissues. In the draining lymph nodes they
      present the immunogenic peptides to T cells thereby inducing antigen-specific
      immune responses. HIV-1 in turn seems to have developed mechanisms to exploit the
      natural trafficking of DC to establish infection in its primary targets, the CD4+
      T cells. This review discusses several aspects of DC-HIV interactions with a main
      focus on the attachment, internalisation and transmission of the virus by DC to
      cells, susceptible for infection with HIV.

PMID- 15488611
TI  - Mutual interference of HIV and natural killer cell-mediated immune response.
AB  - Natural killer (NK) cells represent important early effector cells in innate
      immune defense as they exert their functions without prior sensitization. They
      participate in regulation of innate and adaptive immune responses and
      hematopoiesis by producing various cytokines and chemokines. In addition, NK
      cells lyse virally infected and malignant cells raising them to multifunctional
      members of the first line of defense. Unlike other lymphocytes they lack specific
      antigen receptors. They rather bind cells using ubiquitous molecules and
      communicate via a pattern of receptors specific for MHC-I molecules with their
      counterparts. In general, successful binding of the receptors delivers an
      inhibitory signal to NK cells thus sparing the target cell from lysis. In
      contrast, down-regulated or altered MHC-I expression as frequently observed
      during virus infection or on malignant cells prevents ligation of inhibitory
      receptors and MHC-I paralyzing inhibition and thus inducing lysis of the target
      cell. In human immunodeficiency virus (HIV) infection NK cells are of central
      importance since they can combat viral infection itself and opportunistic
      pathogens like fungi and protozoa that usually spread during the course of HIV
      infection. However, various studies have reported alterations in HIV patients
      affecting NK cell numbers and functions that might negatively influence course
      and severity of the disease. This review will focus on the mutual interference of
      NK cells and the HI virus.

PMID- 15488612
TI  - Innate immunity in experimental SIV infection and vaccination.
AB  - Innate immunity represents the first line of defence to pathogens besides the
      physical barrier and seems to play a role in protection against HIV/SIV infection
      and disease progression. High production of beta-chemokines and CD8+ T cell anti
      viral factors in naive as well as in vaccinated macaques has been associated with
      complete or partial protection against SIV infection indicating that genetic or
      environmental factors may influence their production. This innate immunity may
      help in generating HIV/SIV-specific responses upon the first exposure to HIV/SIV.
      SIV subunit vaccines given by the targeted iliac lymph node route have been shown
      to induce an increased production of CD8+ T cell suppressor factors and beta
      chemokines. Only a few vaccine studies have focused on enhancing the innate
      immune response against HIV/SIV. The use of unmethylated CpG motifs, HSP and GM
      CSF as adjuvants in SIV vaccines has been shown to induce production of HIV/SIV
      inhibiting cytokines and beta-chemokines, which seem to be important in
      modulating and steering the adaptive immune responses. HSP has also been shown to
      induce gammadelta+ T cells, which contribute to the innate immunity. More
      knowledge about the interplay between the innate and adaptive immune responses is
      important to develop new HIV/SIV vaccine strategies.

PMID- 15488613
TI  - Recombinant HIV-1 Pr55gag virus-like particles: potent stimulators of innate and
      acquired immune responses.
AB  - Several previous reports have clearly demonstrated the strong effectiveness of
      human immunodeficiency virus (HIV) Gag polyprotein-based virus-like particles
      (VLP) to stimulate humoral and cellular immune responses in complete absence of
      additional adjuvants. Yet, the mechanisms underlying the strong immunogenicity of
      these particulate antigens are still not very clear. However, current reports
      strongly indicate that these VLP act as "danger signals" to trigger the innate
      immune system and possess potent adjuvant activity to enhance the immunogenicity
      of per se only weakly immunogenic peptides and proteins. Here, we review the
      current understanding of how various particle-associated substances and other
      impurities may contribute to the observed immune-activating properties of these
      complex immunogens.

PMID- 15488614
TI  - Multiplex detection and quantitation of latent and lytic transcripts of human
      herpesvirus-8 using RNase Protection Assay.
AB  - Human herpesvirus-8 (HHV-8, also called Kaposi's sarcoma-associated herpesvirus)
      infectious cycle can be divided into latent and lytic phases. During the latent
      phase viral gene expression is reduced to a minimum, while during the lytic
      phase, numerous genes are expressed sequentially. The development of an RNase
      Protection Assay (RPA) is described that allows the detection and quantitation of
      three latent (ORFs 71-72-73) and three lytic (ORFs 74-K4-K2) HHV-8 genes as well
      as two cellular housekeeping gene transcripts (glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH) and cyclophilin) for normalization purposes is described.
      The RPA was validated using 293T cells transfected with corresponding HHV-8
      expression vectors and using resting and phorbol ester-butyric acid-activated BC
      3 and BCBL-1 cells. The results obtained indicate that this RPA is specific,
      sensitive and allows for the simultaneous monitoring of HHV-8 latent and lytic
      genes expression. HHV-8-RPA is therefore a useful technique to monitor the status
      of HHV-8 infection in infected cells (latent versus lytic) by comparing and
      quantitating multiple viral transcripts expression from a single RNA sample.

PMID- 15488615
TI  - Neuraminidase activity assays for monitoring MDCK cell culture derived influenza
      virus.
AB  - Three assay methods were investigated for monitoring the time-course of
      neuraminidase (NA) activity of tissue culture derived equine influenza A virus
      from large-scale microcarrier cultivation and several steps of downstream
      processing required for the production of inactivated vaccines. Measurements of
      neuraminidase activity by a thiobarbituric acid (TBA) and a fluorometric method
      using Amplex Red as a fluorogen (FL-AR) did not correlate with the increase of
      hemagglutinin (HA) during virus replication. Samples analysed by the TBA method
      showed unspecific interference from low molecular weight compounds (< 3 kDa) of
      cell growth medium and virus maintenance medium. Further investigations showed
      that this was probably caused by interfering reactions between reducing sugars
      and amino acids that can be overcome by dialysis of samples. On the other hand,
      the sensitivity of the FL-AR method was not sufficient for the required measuring
      range. However, a reliable and sensitive fluorometric assay method (FL-MU-NANA)
      was obtained using 4-methylumbelliferyl-alpha-d-N-acetylneuraminic acid (4-MU
      NANA) as a substrate, which allowed the detection of neuraminidase activities as
      low as 0.09 mU/mL. In this assay, time-course of neuraminidase activities
      correlated well with increasing hemagglutinin activities during virus replication
      in a bioreactor. Analysis of samples from various downstream processing steps
      comprising of clarification, inactivation, ultrafiltration (UF) and size
      exclusion chromatography for the purification of influenza virus showed that
      neuraminidase activity was preserved at comparatively high levels. Based on the
      hemagglutinin and neuraminidase activity of the clarified and inactivated virus
      harvest, the overall recovery after gel filtration was about 34.4% and 119.5%,
      respectively.

PMID- 15488616
TI  - Large-scale production, purification and crystallization of wild-type adeno
      associated virus-2.
AB  - Adeno-associated virus-2 (AAV-2) has long been recognized as a potential vector
      for human gene therapy. Although much progress has been made in the molecular
      virology of AAV-2, structural studies of AAV-2 have been hampered by the low
      efficiency of virus production in culture, the low purity of preparations, and
      the low solubility of pure virus particles in solution. Methods of larger scale
      AAV-2 production have been developed through adaptation to suspension culture and
      re-optimization of the times of infection and transfection with respect to
      particle production. The methods allow the purification of 10mg ( approximately
      10(15) particles) of AAV-2 per preparation at approximately 99% purity as judged
      by SDS-PAGE. This was sufficient for the screening of conditions for the
      formation of diffraction-grade crystals, ultimately leading to an atomic
      structure for AAV-2.

PMID- 15488617
TI  - Comprehensive detection and identification of human coronaviruses, including the
      SARS-associated coronavirus, with a single RT-PCR assay.
AB  - The SARS-associated human coronavirus (SARS-HCoV) is a newly described, emerging
      virus conclusively established as the etiologic agent of the severe acute
      respiratory syndrome (SARS). This study presents a single-tube RT-PCR assay that
      can detect with high analytical sensitivity the SARS-HCoV, as well as several
      other coronaviruses including other known human respiratory coronaviruses (HCoV
      OC43 and HCoV-229E). Species identification is provided by sequencing the
      amplicon, although a rapid screening test by restriction enzyme analysis has
      proved to be very useful for the analysis of samples obtained during the SARS
      outbreak in Toronto, Canada.

PMID- 15488618
TI  - Differentiation of Italian field and South African vaccine strains of bluetongue
      virus serotype 2 using real-time PCR.
AB  - The current outbreaks of bluetongue (BT) disease in sheep in the central parts of
      the Mediterranean basin are being combated by extensive vaccination to control
      further spread of the virus and to suppress its long-term maintenance in the
      field. To be able to monitor the success of this campaign, and to be able to
      identify new foci of the disease, it is necessary to harness diagnostic methods,
      both rapid and sensitive, for differentiating reliably field from vaccine strains
      of bluetongue virus (BTV). A new method is described for their differentiation
      using fluorescence resonance energy transfer (FRET) probes with real-time PCR.
      The method is based on the principle that the melting temperature of a DNA duplex
      gives information about the sequence, and allows even double-base alterations in
      the amplicon to be identified. The RT-PCR, the generation of melting curves, and
      fluorescence detection were all performed using the LightCycler system (Roche
      Diagnostics, Mannheim, Germany).

PMID- 15488619
TI  - Evaluation of a norovirus sampling method using sodium dodecyl sulfate/EDTA
      pretreated chromatography paper strips.
AB  - Noroviruses are the most common cause of nonbacterial gastroenteritis outbreaks.
      A novel method was tested that utilizes sodium dodecyl sulfate (SDS)/EDTA
      pretreated chromatography paper strips to collect and transport norovirus
      containing fresh stool samples. As confirmation, the strips were infected with
      different dilutions of human norovirus-containing faeces and stored at different
      temperatures (-80, -20, 4 degrees C, room temperature and 37 degrees C). Reverse
      transcription (RT)-PCR analysis was carried out after storage of the strips for
      1, 7, 14, 60, and 120 days. The presence of amplifiable norovirus RNA on the
      strips was inversely correlated with the duration of storage and the storage
      temperature. Norovirus RNA remained detectable for a sufficient amount of time at
      room temperature or even in warmer climatic conditions to allow transportation of
      the samples from a field site to a reference laboratory using regular postal
      mail. To prove that viral infectivity was lost upon contact with the SDS/EDTA
      treated strips, feline calicivirus F9 (10(7) TCID(50)/ml) was loaded onto the
      strips. After elution and dialysis, no cytopatic effect could be observed upon
      incubation on Crandell-Reese feline kidney cells. The SDS/EDTA-pretreated
      chromatography filter paper strips are an inexpensive, biosafe and adequate
      method to collect, transport and store norovirus samples.

PMID- 15488620
TI  - African horsesickness virus serotyping and identification of multiple co
      infecting serotypes with a single genome segment 2 RT-PCR amplification and
      reverse line blot hybridization.
AB  - Since protection against African horsesickness (AHS) is serotype-specific, rapid
      serotyping of AHSV is crucial to identify the correct vaccine serotype for
      efficient control of the spread of AHS outbreaks, especially when they occur in
      non-endemic regions. This paper describes the first one-day serotyping procedure
      that requires only a single RT-PCR and hybridization and which can identify
      multiple serotypes in mixed infections in one assay. The same region of genome
      segment 2 of all nine AHSV serotypes is amplified in a single RT-PCR. A universal
      primer set, designed to amplify the 5'-terminal 521-553bp of genome segment 2 of
      all of the nine AHSV serotypes with one reaction, was used to generate serotype
      specific probes from dsRNA prepared from infected tissue cultures or organ
      samples. These probes hybridized serotype-specifically with immobilized genome
      segment 2 cDNA of the nine AHSV reference serotypes in a checkerboard reverse
      line blot format. All nine AHSV reference and the seven vaccine strains and field
      viruses isolated up to 28 years apart could be serotyped accurately within a day.
      The sensitivity of the method is 1pg dsRNA which is sufficient to serotype AHSV
      directly from lung and spleen specimens of infected horses.

PMID- 15488621
TI  - Development of a novel real-time RT-PCR assay with LUX primer for the detection
      of swine transmissible gastroenteritis virus.
AB  - Real-time RT-PCR assay, based on light upon extension (LUX) fluorogenic primer
      and LightCycle technology, was developed for rapid detection of transmissible
      gastroenteritis virus (TGEV). Viral RNA from different TGEV isolates and clinical
      specimens was detected. To evaluate the sensitivity of the assay, a gel-based RT
      PCR method targeted at the same 101 bp sequence was also developed. Serial 10
      fold dilutions of TGEV RNA were detected by the two methods. Although the real
      time method used only 2 microl RNA for each reaction, a 10-fold increase of
      sensitivity over that of the gel-based method, which used 10 microl RNA was
      demonstrated. The study indicates that the LUX assay reported below is rapid,
      reliable and sensitive and it has the potential for use as an alternative
      molecular method for TGEV diagnosis.

PMID- 15488622
TI  - MALDI-TOF mass spectroscopy detects the capsid structural instabilities created
      by deleting the myxoma virus cupro-zinc SOD1 homolog M131R.
AB  - The myxoma virus M131R gene encodes a catalytically inactive homolog of cellular
      Cu-Zn superoxide dismutase (SOD1) and this 17,786 Da protein is a major virion
      component. We have used matrix-assisted laser desorption ionization time-of
      flight mass spectroscopy (MALDI-TOF MS) to study the effect(s) of deleting the
      gene on virion composition and structure. This approach confirmed that the M131R
      gene product is an abundant virion component. This conclusion was based upon the
      ready detection of a 1805.3 Da peptide released from the N-terminus of the myxoma
      SOD1 protein by mild trypsin treatment, as well as the detection of a 17,790 Da
      protein in HPLC fractionated virus extracts, which subsequently yielded M131R
      encoded tryptic peptides. Neither peptide nor protein was detected in particles
      bearing a genome encoding an M131RDelta deletion mutation. Curiously, more
      proteins and tryptic peptides were detected when M131RDelta mutant virions were
      subjected to MALDI-TOF MS analysis compared with wild-type virus particles. This
      suggested that particles assembled in the absence of myxoma SOD protein are
      structurally unstable. Plaque analysis confirmed this conjecture by showing that
      SOD-deficient MYX particles are unusually heat labile and trypsin sensitive.
      Mutant Shope fibroma virus exhibited the same phenotype. Thus a previously
      unappreciated feature of MALDI-TOF MS is that the method can sometimes detect
      alterations in virion stability.

PMID- 15488623
TI  - Increased protein expression from adenoviral shuttle plasmids and vectors by
      insertion of a small chimeric intron sequence.
AB  - Adenoviruses are widely used as gene transfer vehicles because they can be
      produced at high titers, they have a large transgene capacity, and can transduce
      both dividing and non-dividing cells. One disadvantage of adenoviral vectors is
      the narrow therapeutic window due to a dose-dependent humoral as well as a T-cell
      dependent host immune response directed against the transduced cells, that leads
      to a reduction of transgene expression with time. By increasing the levels of
      protein expression from transcription units, vector titres may be decreased
      without a significant loss of transgene expression. Introns are required for
      efficient expression of many protein coding genes. In addition, splicing signals
      are required for some genes in order to be translated. Therefore, a chimeric
      intron sequence was introduced at the 3' end of the transgenes to study its
      effect on protein expression from adenoviral vector constructs. Transfection of
      293 cells with the adenoviral shuttle plasmids pMH4-EGFP-Int, pMH4-E314.7-Int,
      pMH4-BclX(L)-Int and pMH4-Luc-Int lead to a 1.8-20-fold increase in protein
      expression as compared to constructs lacking an intron. Injection of Ad-CMV-Luc
      Int into the brain of C57Bl/6 mice results in an approximately three-fold
      increase of luciferase activity as compared to Ad-CMV-Luc. In conclusion,
      insertion of an intron sequence leads to a significant increase in transgene
      expression both in vitro and in vivo, thus allowing for reduction of the
      adenoviral vector dose used.

PMID- 15488624
TI  - Sensitive and reliable detection of grapevine fanleaf virus in a single Xiphinema
      index nematode vector.
AB  - Grapevine fanleaf virus (GFLV) is specifically transmitted from plant to plant by
      the ectoparasitic nematode Xiphinema index. A sensitive and reliable procedure
      was developed to readily detect GFLV in a single viruliferous X. index,
      regardless of the nematode origin, i.e. greenhouse rearings or vineyard soils.
      The assay is based on bead milling to disrupt nematodes extracted from soil
      samples, solid-phase extraction of total nematode RNAs, and amplification of a
      555bp fragment of the coat protein (CP) gene by reverse transcription-polymerase
      chain reaction with two primers designed from conserved sequences. This procedure
      is sensitive since the CP gene fragment is amplified from an artificial sample
      consisting of one viruliferous nematode mixed with 3000 aviruliferous
      individuals. In addition, StyI RFLP analysis of the CP amplicon enables the GFLV
      isolate carried by a single viruliferous X. index to be characterized. This GFLV
      detection assay opens new avenues for epidemiological studies and for molecular
      investigations on the mechanism of X. index-mediated GFLV transmission.

PMID- 15488625
TI  - Nested PCR with the PGMY09/11 and GP5(+)/6(+) primer sets improves detection of
      HPV DNA in cervical samples.
AB  - Based on epidemiological and research evidence, HPV has a causal role in cervical
      carcinogenesis. Several HPV detection methods exist to date; the most commonly
      used method for detection of genital HPVs consists of nested PCR using the
      MY09/11 and GP5(+)/6(+) primer sets (MY/GP(+)). Recently, the PGMY09/11 primer
      set, a modified version of the MY09/11 primer set, was introduced for single PCR
      and was found to detect a wider range of HPV types. The next logical step was
      taken and the efficacy of nested PCR using the PGMY09/11 and GP5(+)/6(+) primer
      sets (PGMY/GP(+)) to detect HPV in cervical samples was evaluated. In this
      comparative study, nested PCR using the novel PGMY/GP(+) primer set combination
      was found to be more type sensitive than the nested PCR with the MY/GP(+) primer
      sets, detecting a wider range of HPV types, low copy HPVs, and better
      characterizing samples infected with multiple strains of HPV. Standardization and
      use of the PGMY/GP(+) PCR system could aid physicians in providing more efficient
      HPV screening and better treatment for patients.

PMID- 15488626
TI  - Detection and relative quantitation of Soil-borne cereal mosaic virus (SBCMV) and
      Polymyxa graminis in winter wheat using real-time PCR (TaqMan).
AB  - Soil-borne cereal mosaic virus (SBCMV) was first reported affecting wheat crops
      in Italy in 1960 and has spread subsequently to many other European countries,
      including the UK. SBCMV causes a serious disease of wheat, reducing yield by up
      to 70%; growing resistant varieties represents the only economical means of
      control. Real-time RT-PCR and PCR assays based on TaqMan chemistry were developed
      for the detection and quantitation of SBCMV and its vector, Polymyxa graminis.
      Each assay incorporated an RNA or DNA specific internal control to facilitate
      quantitation. Nucleic acid extracts from SBCMV-infected plants were diluted in a
      nucleic acid extract from a healthy plant and amplified by real-time PCR to
      produce a standard curve. The standard curve was used to quantify the amount of
      SBCMV and P. graminis in plant samples. The sensitivity of the real-time assays
      were compared to established serological quantitation and conventional PCR
      methods by testing a range of SBCMV-infected wheat varieties. The results
      indicate that real-time assays were a 1000 times more sensitive than ELISA for
      the quantitation of SBCMV, and a 100 times more sensitive than conventional PCR
      for the quantitation of P. graminis. Real-time assays enabled sensitive,
      reproducible and specific detection of both virus and vector in wheat tissues.
      The real-time assays are potentially useful tools for determining variations in
      virus and vector concentrations in plant tissue from wheat varieties differing in
      resistance to SBCMV.

PMID- 15488627
TI  - The expression of SARS-CoV M gene in P. Pastoris and the diagnostic utility of
      the expression product.
AB  - High-level protein expression is an important means of obtaining large amounts of
      viral proteins to investigate further their biological properties. To express the
      membrane (M) protein of SARS-CoV at high-level in vitro, the M gene fragment was
      amplified and cloned it into the Pichia Pastoris expression vector pPICZalphaA.
      SDS-PAGE and Western blotting analysis of the induced products of recombinant
      yeast transformant indicated that successful high-level expression of M protein
      was achieved, and that the expression product was similar antigenically to the
      natural protein. Purified recombinant M protein was used subsequently as an ELISA
      antigen for detection of eight serum samples screened previously by whole virus
      ELISA and immunofluorescence assay, and consistent results were obtained. These
      findings suggest that the recombinant M protein may be useful as a diagnostic
      reagent.

PMID- 15488628
TI  - Development of a chitinase and v-cathepsin negative bacmid for improved integrity
      of secreted recombinant proteins.
AB  - The application of the baculovirus-insect cell expression system for the
      production of integral membrane and secreted proteins is often more troublesome
      than for cytoplasmic proteins. One protein expressed at low levels in insect
      cells is the Theileria parva sporozoite surface protein p67. Theileria parva is a
      protozoan parasite, which causes the tick-transmitted disease East Coast fever in
      cattle. Baculovirus vectors were engineered to produce a secreted form of p67 by
      replacing the signal peptide of p67 with the honeybee mellitin signal sequence
      and deleting a putative membrane anchor from the C-terminus. Furthermore, the
      chitinase and v-cathepsin genes were deleted from the baculovirus expression
      vector in a bacmid setup, allowing broad scale application of this novel vector.
      Deletion of the chitinase and v-cathepsin gene had a positive effect on the
      integrity of both the intracellular and secreted recombinant protein.

PMID- 15488629
TI  - Genetic subtyping of influenza A viruses using RT-PCR with a single set of
      primers based on conserved sequences within the HA2 coding region.
AB  - Influenza A viruses are subtyped conventionally according to the antigenic
      characteristics of the external glycoproteins, haemagglutinin (HA) and
      neuraminidase (NA). To date 15 HA and 9 NA subtypes have been described. There is
      a need to develop fast, accurate and reliable methods to identify influenza virus
      subtypes, which may be associated with disease outbreaks. An RT-PCR is described
      using a single primer pair based on a conserved region of the HA2 gene that can
      detect all 15 HA influenza A subtypes. The assay was validated initially using a
      panel of 12 known standard prototype strains of influenza virus representing 6 HA
      subtypes and subsequently in a blind study using a panel of 30 strains. Selected
      viruses represented all known HA subtypes derived from avian, swine and human
      hosts separated both geographically and with time Sequence analysis of RT-PCR
      product showed complete correlation with results obtained using conventional
      serological methods. It is concluded that this RT-PCR is a reliable, robust and
      reproducible tool for the rapid identification of a wide range of all the HA
      subtypes of influenza A viruses.

PMID- 15488630
TI  - A rapid in vitro polyomavirus DNA replication assay.
AB  - Traditionally, the Hirt extraction method, a multi-step, labor-intensive and time
      consuming procedure, is employed to extract selectively low-molecular weight DNA
      for polyomavirus DNA replication analyses. DNA replication results obtained with
      this approach are often inconsistent between replicate samples. To increase the
      efficiency and reproducibility of the polyomavirus DNA replication assay, we
      compared the DNA quality and yield using Qiagen Spin Column technology and the
      Hirt extraction technique. CV-1 cells transfected with SV40 DNA were harvested at
      days 2, 4, and 6 post-transfection, and DNA was extracted using the Qiagen Spin
      Column and the Hirt extraction methods. Southern hybridization was performed
      using a (32)P-labeled linear full-length SV40 DNA probe. Viral DNA replication
      was quantitated using a BioRad phosphorimager, and results obtained with the two
      procedures were compared. Southern blot analysis revealed consistent and enhanced
      SV40 DNA recovery using the Qiagen Spin Column technology, and viral DNA
      replication over a 6-day period was reproducible among triplicate samples. In
      addition, Qiagen Spin Column technology reduced the time required to obtain good
      quality DNA for polyomavirus replication assays from 24 h to less than 3 h.
      Adoption of this extraction procedure will improve the determination of
      polyomavirus DNA replication activity, while reducing the investigator's exposure
      to and disposal of toxic organic compounds.

PMID- 15488631
TI  - Role of chemopreventive agents in cancer therapy.
AB  - Tumorigenesis or carcinogenesis is a multi-step process that is induced primarily
      by carcinogens leading to the development of cancer. Extensive research in the
      last few years has revealed that regular consumption of certain fruits and
      vegetables can reduce the risk of acquiring specific cancers. Phytochemicals
      derived from such fruits and vegetables, referred to as chemopreventive agents
      include genistein, resveratrol, diallyl sulfide, S-allyl cysteine, allicin,
      lycopene, capsaicin, curcumin, 6-gingerol, ellagic acid, ursolic acid, silymarin,
      anethol, catechins and eugenol. Because these agents have been shown to suppress
      cancer cell proliferation, inhibit growth factor signaling pathways, induce
      apoptosis, inhibit NF-kappaB, AP-1 and JAK-STAT activation pathways, inhibit
      angiogenesis, suppress the expression of anti-apoptotic proteins, inhibit
      cyclooxygenase-2, they may have untapped therapeutic value. These chemopreventive
      agents also have very recently been found to reverse chemoresistance and
      radioresistance in patients undergoing cancer treatment. Thus, these
      chemopreventive agents have potential to be used as adjuncts to current cancer
      therapies.

PMID- 15488632
TI  - Mechanism of carcinogenesis induced by a veterinary antimicrobial drug,
      nitrofurazone, via oxidative DNA damage and cell proliferation.
AB  - Nitrofurazone, a veterinary antimicrobial drug, causes mammary and ovarian tumors
      in animals. We investigated the mechanisms of carcinogenesis by nitrofurazone.
      Nitrofurazone significantly stimulated the proliferation of estrogen-dependent
      MCF-7 cells. Nitrofurazone caused Cu(II)-mediated damage to 32P-5'-end-labeled
      DNA fragments obtained from human genes only when cytochrome P450 reductase was
      added. DNA damage was inhibited by catalase and bathocuproine. DNA damage was
      preferably induced at the 5'-ACG-3' sequence, a hotspot of the p53 gene. These
      findings suggest that nitrofurazone metabolites are involved in tumor initiation
      through oxidative DNA damage and nitrofurazone itself enhances cell
      proliferation, leading to promotion and/or progression in carcinogenesis.

PMID- 15488633
TI  - Differential mutagenicity of riddelliine in liver endothelial and parenchymal
      cells of transgenic big blue rats.
AB  - Riddelliine is a naturally occurring pyrrolizidine alkaloid that induces liver
      hemangiosarcomas in rats and mice. We previously reported higher levels of DNA
      adducts in liver endothelial cells than in liver parenchymal cells of riddelliine
      treated mice and rats [Cancer Lett. 193 (2003) 119], suggesting that the tumor
      specificity is due to higher levels of DNA damage in the cells that form
      hemangosarcomas. In the present study, we evaluated the cell-specificity of
      riddelliine mutagenicity in rat liver. Female transgenic Big Blue rats were
      treated by gavage with 0.3 mg riddelliine per kg body weight, 5 days a week for
      12 weeks. One day after the last treatment, the rats were sacrificed and liver
      parenchymal and endothelial cell fractions were isolated and purified. DNA was
      extracted from the cell fractions and used to assay for mutant frequency (MF) in
      the cII transgene. While there was no difference in the cII MFs of liver
      parenchymal cells in control and riddelliine-treated rats, the cII MF of liver
      endothelial cells from treated rats was significantly greater than the cII MF of
      endothelial cells from control rats. Molecular analysis of the mutants in liver
      endothelial cells indicated that G:C-->T:A transversion, a mutation that is
      characteristically induced by riddelliine, accounted for only 9% of all mutations
      in control rats, but made up 17% of mutations in treated rats. In contrast, G:C-
      >A:T transition, the major mutation in control rats where it made up 54% of all
      mutations, was reduced to 40% of mutations in riddelliine-treated rats. These
      results suggest that the relatively high mutagenicity of riddelliine in rat liver
      endothelial cells may be partially responsible for the tumorigenic specificity of
      this agent.

PMID- 15488634
TI  - Inhibition of proliferation and induction of apoptosis by genistein in colon
      cancer HT-29 cells.
AB  - Genistein has multiple anticancer properties. However, its mechanisms of action
      and its molecular targets on human colon cells remain to be further elucidated.
      Here, we demonstrated that genistein reduced proliferation and induced G2/M phase
      arrest and apoptotic death in colon cancer HT-29 cells. We then investigated the
      effects of genistein on molecules that regulate apoptosis and cell cycle
      progress. Genistein increased expression of Bax and p21WAF1 and slightly
      decreased Bcl-2 level. Our results demonstrated that genistein inhibited the
      viability of human colon cancer HT-29 cell via induction of apoptosis mainly
      through regulation of p21WAF1 and Bax/Bcl-2 expression. These data suggested a
      role of genistein in prevention of colon tumor and might reduce colon tumor
      growth.

PMID- 15488635
TI  - Distribution and subcellular localization of a water-soluble hematoporphyrin
      platinum(II) complex in human bladder cancer cells.
AB  - The water-soluble porphyrin-platinum complex diammine[7,12-bis[1
      (polyethyleneglycol-750-monomethylether-1-yl)ethyl]-3,8,13,17
      tetramethylporphyrin-2,18-dipropionato]platinum(II) (PEG-HPPt) was studied with
      respect to cellular accumulation, subcellular localization, behavior in 3D-cell
      aggregates and degree of DNA platination on the low-differentiated J82 cells, a
      model of invasive bladder cancer, and UROtsa, a normal urothelial cell line.
      Accumulation studies with 2D and spheroid cell cultures revealed that the
      concentration of PEG-HPPt was 1.7-times higher in J82 cancer cells than in UROtsa
      cells. Despite its high molecular weight, penetration of PEG-HPPt was not
      restricted to the peripheral cells of the spheroids. Fluorescence microscopic
      analysis showed that PEG-HPPt was localized in essential cellular targets of
      photodynamic therapy. DNA platination in J82 and UROtsa cells was higher by PEG
      HPPt than by cisplatin, whereas there was no significant difference between the
      two cell lines.

PMID- 15488636
TI  - Antitumor effect induced by dendritic cell (DC)-based immunotherapy against
      peritoneal dissemination of the hamster pancreatic cancer.
AB  - Establishing a method to control peritoneal dissemination is one of the most
      pressing issues in the postsurgical treatment of pancreatic cancer. In the
      present study, we investigated the effect of dendritic cell (DC)-based
      immunotherapy on peritoneal disseminations of hamster pancreatic cancer cells,
      PGHAM-1. After the orthotopically inoculation of 2 x 10(6) PGHAM-1 cells, DC
      pulsed with PGHAM-1-derived tumor lysates, DC alone or PBS as a vehicle was
      injected intraperitoneally (i.p.) three times at weekly intervals. The group
      treated with DC or DC+lysate was found to have smaller disseminated tumors than
      the vehicle-treated. In addition, mean survival time in the DC+lysate groups was
      significantly longer than the PBS group. These findings suggested that DC-based
      immunotherapy might be efficient for the treatment of peritoneal disseminations
      of the pancreatic cancer.

PMID- 15488637
TI  - Analysis of familial male breast cancer for germline mutations in CHEK2.
AB  - We have previously shown that the1100delC variant of the cell-cycle-checkpoint
      kinase gene CHEK2, which is carried by approximately 1% of the population confers
      a two-fold increase in female breast cancer and a 10-fold increase in male breast
      cancer. To extend our knowledge on the role of CHEK2 in susceptibility to male
      breast cancer we have screened a series of 26 breast cancer cases with male
      representation for germline sequence variation in the CHEK2 gene. One individual
      was found to harbour the 1100delC variant. No other mutations were identified.
      Variants other than 1100delC are rare in male breast cancer.

PMID- 15488638
TI  - Interleukin-1B gene promoter variants are associated with an increased risk of
      gastric cancer in a Chinese population.
AB  - Studies suggest that IL-1beta (encoded by IL-1B gene) is a pro-inflammatory
      cytokine and potent inhibitor of gastric acid secretion, which is proposed as a
      key determinant in gastric carcinogenesis. Two potentially functional
      polymorphisms (C-31T and T-511C) in the IL-1B promoter were suggested to be
      correlated with alteration of Helicobacter pylori infection and IL-1beta
      expression and therefore may be associated with risk of gastric cancer. To test
      the hypothesis that these two polymorphisms are associated with gastric cancer
      risk, we performed a case-control study of 280 histologically confirmed gastric
      cancer patients and 258 age, sex frequency-matched cancer-free controls in a
      Chinese population. Multivariate logistic regression analyses revealed that the
      risks (adjusted odds ratio [OR] and 95% confidence interval [CI]) associated with
      the IL-1B variant genotypes were 1.64 (95% CI, 1.01-2.66) for -31TT and 1.52 (95%
      CI, 0.91-2.54) for -511CC, respectively, compared with their wild-type
      homozygotes. The risks were significantly more evident in individuals with H.
      pylori infection (adjusted OR, 2.14; 95% CI, 1.13-4.06 for -31TT; adjusted OR,
      2.00; 95% CI, 1.02-3.89 for -511CC), which was consistent with the biological
      effects of IL-1beta. When we used the haplotype analyses and assumed the IL-1B 
      31T and -511C as risk alleles, no synergistic effect was found between these two
      loci. These findings indicate that these two IL-1B promoter variants may
      contribute to the risk of developing gastric cancer in the Chinese population,
      especially in individuals with H. pylori infection.

PMID- 15488639
TI  - Physalis peruviana extract induces apoptosis in human Hep G2 cells through
      CD95/CD95L system and the mitochondrial signaling transduction pathway.
AB  - Physalis species is a popular folk medicine used for treating cancer, leukemia,
      hepatitis and other diseases. Studies have shown that the ethanol extract of
      Physalis peruviana (EEPP) inhibits growth and induces apoptotic death of human
      Hep G2 cells in culture, whereas proliferation of the mouse BALB/C normal liver
      cells was not affected. In this study, we performed detailed studies to define
      the molecular mechanism of EEPP-induced apoptosis in Hep G2 cells. The results
      further confirmed that EEPP inhibited cell proliferation in a dose- and time
      dependent manner. At 50 microg/ml, EEPP significantly increased the accumulation
      of the sub-G1 peak (hypoploid) and the portion of apoptotic annexin V positive
      cells. EEPP was found to trigger apoptosis through the release of cytochrome c,
      Smac/DIABLO and Omi/HtrA2 from mitochondria to cytosol and consequently resulted
      in caspase-3 activation. Pre-treatment with a general caspase inhibitor (z-VAD
      fmk) prevented cytochrome c release. After 48 h of EEPP treatment, the apoptosis
      of Hep G2 cells was found to associate with an elevated p53, and CD95 and CD95L
      proteins expression. Furthermore, a marked down-regulation of the expression of
      the Bcl-2, Bcl-XL and XIAP, and up-regulation of the Bax and Bad proteins were
      noted. Taken together, the present results suggest that EEPP-induced Hep G2 cell
      apoptosis was possibly mediated through the CD95/CD95L system and the
      mitochondrial signaling transduction pathway.

PMID- 15488640
TI  - Expression and regulation of MIM (Missing In Metastasis), a novel putative
      metastasis suppressor gene, and MIM-B, in bladder cancer cell lines.
AB  - It has been proposed that a 356 amino acid protein encoded by the MIM (Missing In
      Metastasis) gene on Chromosome 8q24.1, is a bladder cancer metastasis suppressor.
      Recently, Machesky and colleagues [Biochem. J. 371 (2003) 463] identified MIM-B,
      a 759 amino acid protein, of which the C-terminal 356 amino acids are almost
      identical to MIM. Importantly, PCR primers and Northern Blotting probes used in
      the studies of MIM in bladder cancer did not distinguish between sequences
      specific for MIM or MIM-B, thus the importance of either protein to bladder
      cancer remains unclear. We have used primer sequences specific for either MIM or
      MIM-B to explore the possible functional significance of MIM and MIM-B to bladder
      cancer cell behaviour. We have compared MIM and MIM-B mRNA levels in a non
      tumourigenic, non-invasive, transformed uro-epithelial cell line versus 15
      bladder cancer cell lines of differing in vitro invasive abilities, as well as in
      five cell lines clonally isolated from the BL17/2 bladder tumour cell line, whose
      in vitro and in vivo invasive abilities have been determined. MIM and MIM-B mRNA
      levels varied widely between cell lines. Down-regulation of MIM and MIM-B
      occurred in 6/15 (40%) lines but lines showing down-regulation differed between
      MIM and MIM-B. Reduced levels of MIM and MIM-B in BL17/2 were further reduced in
      2/5 (40%) sublines (MIM and MIM-B). Importantly, there was no association between
      MIM or MIM-B expression and invasive behaviour in vivo or in vitro. Treatment of
      representative cell lines with 5-aza-2-deoxycytidine failed to induce MIM or MIM
      B expression. Furthermore, there was no association between MIM or MIM-B mRNA
      levels and p53 functional status. Our data indicate that down-regulation of MIM
      and/or MIM-B expression can occur in bladder cancer cell lines but is not
      associated with increased invasive behaviour. Our data also suggest that in those
      cell lines with reduced levels of MIM and MIM-B mRNA, down-regulation is unlikely
      to be due to promoter hypermethylation or loss of p53 function.

PMID- 15488641
TI  - Identification of a minimal deletion region on chromosome 5q in Chinese
      esophageal squamous cell carcinomas.
AB  - The existence of unknown tumor suppressor gene(s) other than the APC gene has
      been hinted on 5q for esophageal squamous cell carcinoma (ESCC). In order to
      define minimal deletion intervals on 5q in ESCC and investigate the potential
      tumor suppressor gene(s), 9 microsatellite markers scattering the region from
      5q22 to 5q35 were chosen for loss of heterozygosity (LOH) analysis in 50 primary
      ESCC from northern China. The results showed that six cases presented coexistence
      of LOH for three consecutive adjacent chosen markers, suggesting a minimal
      deletion region covering approximately 272 kb located on 5q23 from D5S1384 to
      D5S1505. It was a novel deletion region that was so far never reported in ESCC.
      Significant higher frequencies of LOH were observed in tumors with lower
      pathological grade at the locus D5S820 and with lymph node metastasis at the
      locus D5S408. The data suggested the possibility that one or more putative
      candidate tumor suppressor gene(s) on 5q23 might play an important role in the
      development and/or progression of ESCC.

PMID- 15488642
TI  - The Zn-finger domain of RIZ protein promotes MCF-7 cell proliferation.
AB  - In order to understand the oncogenic properties of retinoblastoma-interacting
      zinc-finger (RIZ) gene products, we produced an MCF-7-derived cell line
      expressing a fusion protein containing the zinc-finger (aa 359-497) domain of RIZ
      protein (MCF-7/znf). The Zn-finger domain contains three of the eight putative Zn
      finger motifs and is located in proximity of the E1A-like domain containing the
      Rb protein-binding motif. The MCF-7/znf cells showed a higher growth rate than
      the parental or the control cell lines, both in hormone-deprived conditions or
      upon estrogen stimulation. Furthermore, they were less sensitive to the growth
      inhibitory effect of anti-estrogens and showed a higher level of expression of
      cyclin D1 and A. The expressed Zn-finger domain recombinant product was localized
      in the nucleus and in the nucleoli and its expression modified the pattern of
      actin staining in the cytoplasm. In conclusion the presented results indicated
      that the Zn-finger domain could be endowed with the putative oncogenic activity
      of RIZ2 gene product.

PMID- 15488643
TI  - ERK1/2 and p38 pathways are required for P2Y receptor-mediated prostate cancer
      invasion.
AB  - The G protein-coupled P2Y purinoceptors have wide physiological functions, but
      their role(s) in tumor progression remain unclear. Here, we report that
      stimulation of P2Y receptors enhances prostate cancer cell invasion in two human
      prostate carcinoma cell lines, which is mediated by ERK1/2 and p38 signaling
      pathways. P2Y agonists stimulated prostate cancer cell invasion, and increased
      the activities of ERK1/2 and p38 protein kinases. The stimulated cancer cell
      invasion was inhibited by the presence of MEK1 inhibitor PD98059 or p38 inhibitor
      SB203580. Expression of dominant-negative mutant of MEK1 (KA-MEK1), or up
      regulation of MKP-5 (a dual-specificity phosphatase of p38), both reduced the
      invasion of cultured prostate cancer cells. These results suggest that P2Y
      receptors and their down-stream ERK1/2 and p38 protein kinases are important
      regulators promoting prostate cancer invasion.

PMID- 15488644
TI  - Seasonal affective disorder: a vestigial evolutionary advantage?
AB  - The typical symptoms of recurrent winter depression include lowered mood,
      lethargy, hypersomnia, social withdrawal, decreased libido, increased appetite
      and weight gain. Mild hypomania often occurs in spring and summer. It is argued
      that this pattern of attenuated hibernation constituted an adaptive evolutionary
      mechanism which enhanced the likelihood of reproductive success, most notably for
      females, among populations living at temperate latitudes. Women were more likely
      to become pregnant in the summer and thus to give birth at a time of year when
      their babies had a higher chance of survival. Winter depression symptoms also
      promoted healthier pregnancies and gave rise to enhanced female-male pair-bonding
      which improved the survival chances of both mothers and babies. Hypomania in
      spring and summer also served to increase the likelihood of procreation at the
      optimal time of year. In the modern era, it is probable that recurrent winter
      depression is becoming a reproductive disadvantage.

PMID- 15488645
TI  - Recycling of pathogenic microbes through survival in ice.
AB  - Viable microorganisms (e.g. fungi, bacteria, Archaea and viruses) are distributed
      by wind over great distances, including globally. Microbes may settle out of the
      atmosphere or may be incorporated into fog, rain, sleet, hail, or snow. These
      organisms fall into lakes, streams, oceans, or onto the land or glaciers. When
      they become incorporated into environmental ice (e.g. glaciers, ice sheets, and
      snow), those that survive freezing and thawing may persist for years, centuries,
      millennia, or longer. Once they melt from the ice, they may enter contemporary
      populations. This mixing of ancient and modern genotypes (i.e. temporal gene
      flow, or what we term "genome recycling") may lead to a change of allele
      proportions in the population, which may have effects on mutation rates, fitness,
      survival, pathogenicity and other characteristics of the organisms. Pathogenic
      microbes that survive freezing and thawing (e.g. influenza viruses, polioviruses,
      caliciviruses and tobamoviruses) can remain in these icy reservoirs long enough
      to avoid resistance mechanisms of the hosts, thereby conveying a selective
      advantage to these pathogens over those that cannot survive in ice. Ice is an
      abiotic reservoir of microbes that has been ignored in surveillance activities
      for human diseases.

PMID- 15488646
TI  - Debunking a myth: neurohormonal and vagal modulation of sleep centers, not
      redistribution of blood flow, may account for postprandial somnolence.
AB  - It is widely believed that postprandial somnolence is caused by redistribution of
      blood flow from cerebral to mesenteric vessels after a meal. This belief persists
      despite its apparent contradiction with a well-known neurophysiologic principle
      that cerebral perfusion is preferentially maintained under a wide range of
      physiologic states. For instance, during exercise when a large amount of
      perfusion is diverted to muscles, blood flow to the brain is maintained.
      Furthermore, recent evidence suggests that there is no measurable change of blood
      flow in the common carotid artery during postprandial states. We propose an
      alternative hypothesis that postprandial release of gut-brain hormones and
      activation of vagal afferents may play a role in postprandial somnolence through
      modulation of sleep centers such as the hypothalamus. Feeding alters the milieu
      of hormones such as melatonin and orexins and also promotes central vagal
      activation. Emerging evidence suggest that these pathways are also modulators of
      neural sleep centers. Potential adaptive explanations of postprandial somnolence
      are explored from a Darwinian perspective.

PMID- 15488647
TI  - Facial fat and its relationship to abdominal fat: a marker for insulin
      resistance?
AB  - Reports of relationships between measures of insulin sensitivity and measures of
      body fat and fat distribution suggest that abdominal fat accumulation is a
      predictor of insulin resistance. It has been previously suggested that facial fat
      (primarily in the cheeks and neck) is strongly associated with visceral abdominal
      fat accumulation. The facial fat is a rich vascular region, that seems to be
      metabolically active and resembles abdominal white adipose tissue. We, therefore,
      hypothesize that facial fat could be a good predictor of insulin resistance.
      Whether facial fat can be used as an accurate marker for insulin resistance
      remains to be determined.

PMID- 15488648
TI  - "Constitutive" skin pigmentation: a marker of breast cancer risk?
AB  - There is much evidence to support a link between oestrogen and breast cancer.
      Both adult and foetal oestrogen may have this predisposing effect, and between
      individual and between-population differences in oestrogen may account for much
      of the variation in risk for breast cancer. Here we suggest that "constitutive"
      skin colour in women is a marker for prenatal and adult oestrogen levels such
      that within ethnic groups light-skinned women have experienced higher in utero
      and adult oestrogen than dark-skinned women. Scores for 'constitutive' skin
      pigment may therefore be predictive of risk for breast cancer and low scores
      could be used to identify individuals at high risk.

PMID- 15488649
TI  - Obesity: an endocrine tumor?
AB  - Obesity is one of the most common disorders in clinical practice. The prevalance
      of obesity has increased by more than 60% since 1990. Adipose tissue acts as an
      endocrine organ secreting many factors into the blood, known as adipokines,
      including leptin, adipsin, acylation-stimulating protein, adiponectin, etc. This
      article examines the hypothesis that obesity may be evaluated as an endocrine
      tumor, regarding its genetic basis, hyperplasia and hypertrophy of adipocytes,
      neovascularisation within the adipose tissue associated with growth, and
      beneficisal metabolic effects of surgical removal of excess adipose tissue by
      liposuction. Assuming obesity as an endocrine tumor may bring out new treatment
      modalities. Liposuction as "cytoreductive surgery", antiangiogenic teraphy or
      anti-neoplastic drugs may be important components of obesity treatment in future.

PMID- 15488650
TI  - Elevated levels of ferrimagnetic metals in foodchains supporting the Guam cluster
      of neurodegeneration: do metal nucleated crystal contaminants [corrected] evoke
      magnetic fields that initiate the progressive pathogenesis of neurodegeneration?
AB  - Elevated levels of aluminium (Al), strontium (Sr), barium (Ba), iron (Fe),
      manganese (Mn) cations - combined with deficiencies of magnesium (Mg)/calcium
      (Ca) - have been observed in the foodchains that traditionally support the
      Chamorro populations affected by high incidence clusters of Alzheimer (AD),
      Parkinson-like (PD), motor neurone diseases and multiple sclerosis on the island
      of Guam. Soils drawn from the cluster region demonstrated an excessive fivefold
      increase in 'magnetic susceptibility' readings in relation to soils from disease
      free adjoining regions. A multifactorial aetiological hypothesis is proposed that
      pivots upon the combined exposure to high levels of natural/industrial sources of
      ferrimagnetic/ferroelectric compounds incorporating Al, Fe, Mn, Sr, Ba (e.g., via
      yam/seafood consumption or exposure to world war 2 (WW2) munitions) and to low
      levels of Mg/Ca in all S. Pacific locations where these clusters of
      neurodegenerative disease have simultaneously erupted. Once gut/blood brain
      barrier permeability is impaired, the increased uptake of Al, Fe, Sr, Ba, or Mn
      into the Mg/Ca depleted brain leads to rogue metal substitutions at the Mg/Ca
      vacated binding domains on various enzyme/proteoglycan groups, causing a broad
      ranging disruption in Mg/Ca dependent systems - such as the glutamine synthetase
      which prevents the accumulation of neurotoxic glutamate. The rogue metals chelate
      sulphate, disrupting sulphated-proteoglycan mediated inhibition of crystal
      proliferation, as well as its regulation of the Fibroblast growth factor receptor
      complex which disturbs the molecular conformation of those receptors and their
      regulation of transphosphorylation between intracellular kinase domains;
      ultimately collapsing proteoglycan mediated cell-cell signalling pathways which
      maintain the growth and structural integrity of the neuronal networks. The
      depression of Mg/Ca dependent systems in conjunction with the progressive
      ferrimagnetisation of the CNS due to an overload of rogue
      ferroelectric/ferrimagnetic metal contaminants, enables 'seeding' of metal
      protein crystalline arrays that can proliferate in the proteoglycan depleted
      brain. The resulting magnetic field emissions initiate a free radical mediated
      progressive pathogenesis of neurodegeneration. The co-clustering of these various
      types of disease in select geographical pockets around the world suggests that
      all of these conditions share a common early life exposure to ferromagnetic metal
      nucleating agents in their multifactorial aetiology. Factors such as individual
      genetics, the species of metal involved, etc., dictate which specific class of
      disease will emerge as a delayed neurotoxic response to these environmental
      insults.

PMID- 15488651
TI  - Gene therapy for the circumvention of inborn errors of metabolism (IEM) caused by
      single-nucleotide-polymorphisms (SNPs).
AB  - Single nucleotide polymorphisms (SNPs) are the result of point mutations in
      nuclear (and mitochondrial) DNA. Such localised damage to DNA (and its
      replicative mechanisms) may not be excised fully by the DNA repair mechanism in
      the genome: and therefore can become inheritable; subsequently to manifest later
      as an inborn error of metabolism (IEM). Causes of mutagenic damage to the DNA can
      include background radiation (such as emitted by radon gas), and by reactive
      oxygen species (ROS): and also by mutagenic chemicals that occur naturally (inter
      alia in the diet). Other causes of DNA damage are variable environmental hazards
      such as solar-derived short wave ultraviolet light A. Gene therapy involves the
      placement of missing genes into particular tissues by the harnessing of suitable
      vectors (originally these were animal viruses such as SV40). For example, gene
      therapy in the rat for diabetes has succeeded by liver-production of insulin
      (using genes obtained from pancreatic Islets of Langerhans cells). Many inborn
      errors of metabolism could be treated in this way: examples may include 100
      haemoglobinopathies (such as sickle cell anaemia), phenylketonuria; and other
      diseases caused by lack of tissue-production of a particular enzyme (in its
      catalytically-active conformation).

PMID- 15488652
TI  - Proposal for a dietary "phytochemical index".
AB  - There is ample reason to believe that diets rich in phytochemicals provide
      protection from vascular diseases and many cancers; direct antioxidant activity
      as well as modulation of enzyme expression or hormone activity contribute to this
      effect. Phytochemicals derived from diverse foods presumably can interact
      additively and (possibly) synergistically; thus, the total dietary load of
      phytochemicals may have important implications for health. As a means of very
      roughly quantifying this load, a "phytochemical index" (PI) is proposed, defined
      as the percent of dietary calories derived from foods rich in phytochemicals.
      Calories derived from fruits, vegetables (excluding potatoes), legumes, whole
      grains, nuts, seeds, fruit/vegetable juices, soy products, wine, beer, and cider 
      and foods compounded therefrom - would be counted in this index. Partial credit
      could be given for antioxidant-rich extra virgin olive oil. Other added oils,
      refined sugars, refined grains, potato products, hard liquors, and animal
      products - regrettably, the chief sources of calories in typical Western diets -
      would be excluded. Although the PI would provide only a very rough approximation
      of the quantity or quality of phytochemical nutrition, it nonetheless could aid
      epidemiologists in exploring the health consequences of diets high in
      phytochemical-rich plant foods, and could also help clinical nutritionists in
      their efforts to improve the phytochemical nutrition of their clients.

PMID- 15488653
TI  - Concurrent treatment with an ACE inhibitor may amplify the utility of calcium
      supplementation for control of hypertension.
AB  - Although supplemental calcium typically lowers blood pressure in subjects with
      salt-sensitive, low-renin hypertension - presumably by down-regulating increased
      production of parathyroid hormone (PTH) and/or parathyroid hypertensive factor
      (PHF) - its impact on the blood pressure of unselected hypertensive or
      normotensive subjects, as assessed by meta-analyses, appears to be trivial at
      best. This suggests that calcium may actually raise blood pressure a bit in some
      patients with high-renin hypertension, a prediction that is borne out in rodent
      models of this disorder. There is limited clinical evidence that long-term
      calcium supplementation tends to raise plasma renin activity; this finding, if
      valid, could evidently rationalize the equivocal clinical impact of calcium on
      blood pressure. Salt restriction likewise boosts renin production, and this
      effect tends to most notable in subjects whose blood pressure fails to decline
      during low-salt diets. Two clinical groups have demonstrated that salt
      restriction has a larger and more consistently beneficial impact on the blood
      pressure of hypertensives when they concurrently are treated with ACE inhibitors 
      evidently because the physiological impact of the associated rise in renin is
      blunted. Analogous logic suggests that calcium supplementation may be more
      beneficial for hypertensives in the context of ACE inhibition or blockade of
      angiotensin II receptors; this supposition that can readily be tested clinically.
      The imminent availability of safe nutraceutical ACE inhibitors may make it more
      feasible for the general public to benefit from these therapeutic/preventive
      possibilities.

PMID- 15488654
TI  - Possible interaction between activator protein-1 and proto-oncogene B-cell
      lymphoma gene 6 in breast cancer patients resistant to tamoxifen.
AB  - About 75% of breast tumors are positive for the estrogen receptor (ER) or
      progesterone receptor (PgR) or both, and estrogen is the main stimulant in the
      development and growth of these tumors. Tamoxifen, an estrogen receptor
      antagonist has been endocrine treatment for hormone-sensitive breast cancer for
      more than 20 years. However, the underlying cause of treatment failure in many
      breast cancer patients receiving tamoxifen is resistance to tamoxifen. The
      mechanisms of tamoxifen and the molecular events responsible for resistance to
      tamoxifen are not fully understood. Two ER subtypes, ERalpha and ERbeta, activate
      the Activator Protein-1 (AP-1) response elements, and through interactions
      between ERs and the AP-1 transcription factors c-fos and c-jun, these
      transcription factors regulate the genes involved in many cellular processes,
      including proliferation, differentiation, cell motility, and apoptosis. Thus, the
      interaction between ERs and AP-1 could be important clinically and could have
      bearing on the response to tamoxifen. Tamoxifen acts as an agonist on genes under
      the control of an AP-1 response elements when ERalpha or ERbeta is expressed. AP
      1 blockade suppresses mitogenic signals from multiple different peptide growth
      factors as well as estrogen, and inhibits the growth of MCF-7 breast cancer cells
      both in vitro and in vivo. Tamoxifen actually activate the AP-1 transcription
      factor. Increased AP-1 activity in breast cancer cells can lead to tamoxifen
      resistance. The proto-oncogene B-cell lymphoma gene 6 (BCL-6) has been
      characterized as a regulator of B-lymphocyte growth and development. BCL-6 is
      also expressed in the mammary epithelium in nonpregnant animals and during early
      pregnancy and is expressed in 68% of histologically high-grade ductal breast
      carcinomas, which are clinically the most aggressive. BCL-6 is a potent repressor
      of transcriptional activity mediated by AP-1 factors. We hypothesize that
      increased BCL-6 in breast cancer cells might block tamoxifen resistance by
      repressing AP-1, eventually resulting in apoptosis. We also suggest that BCL-6
      expression must be analyzed in ER-positive breast cancer patients and the results
      must be correlated with predictive and prognostic factors and survival.

PMID- 15488655
TI  - Unifying concept for Alzheimer's disease, vascular dementia and normal pressure
      hydrocephalus - a hypothesis.
AB  - The three common forms of dementias in the elderly include Alzheimer's disease
      (AD), vascular dementia (VD) and normal pressure hydrocephalus (NPH). These
      disorders are distinguished by their specific pathological features. However,
      overlapping clinical and imaging features in a given case are not too uncommon.
      Based on alterations in CSF dynamics study, a unifying concept in the
      pathogenesis of AD and NPH has been proposed recently which may have therapeutic
      implications. Altered CSF dynamics by affecting the absorptive process may lead
      to hydrocephalic change. This may also affect clearance of amyloid protein
      leading to increased amyloid deposition in brain parenchyma resulting in AD
      pathology. Hence it is likely that a subgroup of patients may have an AD-NPH
      syndrome who may be benefitted by CSF drainage procedure. The present author
      attempts to extend this concept to hypothesise a unifying concept to explain the
      pathophysiology of all the three disorders which may explain overlapping features
      observed clinically and in neuroimaging studies. It is surmised that altered CSF
      dynamics and hypoperfusion from vascular disease may be interlinked. The
      defective clearance of amyloid may also lead to amyloid angiopathy perpetuating
      hypoperfusion. Hypoperfusion may also affect formation as well as absorption of
      CSF altering clearance of amyloid and promoting vascular and parenchymal
      deposition. Thus the pathologies of AD, VaD and NPH get interrelated.

PMID- 15488656
TI  - S-adenosylhomocysteine hydrolase, S-adenosylmethionine, S-adenosylhomocysteine:
      correlations with ribavirin induced anemia.
AB  - Objective is to speculate on the ribavirin induced anemia by inhibiting S
      adenosylhomocysteine (SAH)-hydrolase activity. The major toxicity associated with
      the use of ribavirin is hemolytic anemia. This adverse effect has been ascribed
      to the accumulation of ribavirin triphosphate in the erythrocyte, which
      interferes with erythrocyte function. Ribavirin has been found to inhibit SAH
      hydrolase activity in erythrocyte. SAH is further hydrolyzed to adenosine and
      homocysteine by SAH-hydrolase. The formation of S-adenosylmethionine (SAM) is
      then demethylated to SAH. SAH, the metabolite of SAM, on the other hand is a
      powerful inhibitor of methyltransferase enzymes, competing for the SAM binding
      site. A concurrent decrease in SAM and an increase in SAH levels would inhibit
      methylation of many tissue components including proteins, DNA, RNA, phospholipids
      and other small molecules. The enzyme protein carboxyl methyltransferase type II
      has been recently shown to play a crucial role in the repair of damaged proteins.
      SAM is the methyl donor of the reaction, and its demethylated product, SAH is the
      natural inhibitor of this reaction, as well as of most SAM-dependent
      methylations. The biological function of this transmethylation reaction is
      related to the repair or degradation of age-damaged proteins. Methyl ester
      formation in erythrocyte membrane proteins has been used as a marker reaction to
      tag these abnormal residues and to monitor their increase associated with
      erythrocyte ageing diseases. Liver disease is complicated by cholesterol
      deposition in hepatic and extrahepatic membranes. Erythrocyte membrane fluidity
      has been improved with the administration of SAM and correlated with the
      cholesterol/phospholipid ratio of the membranes. The levels of SAH-hydrolase
      activity were also found to undergo a sharp decrease with red cell ageing. The
      similarity of these alterations with certain morphofunctional characteristics of
      erythrocyte in some conditions as chronic renal failure, liver disease and
      hereditary spherocytosis makes it possible to hypothesize that the inhibition of
      SAH-hydrolase could constitute at least a part of ribavirin induced hemolytic
      anemia.

PMID- 15488657
TI  - On scrapie interference and artificial prions.
AB  - The mechanisms responsible for neuronal death in transmissible spongiform
      encephalopathies (TSEs) are still not completely understood, and at least two
      major hypotheses have been formulated, based on the peculiar aspects of prion
      protein biology. In fact, the neuronal spreading of the prion conformational
      change may lead either to gain toxic properties, or to loose the normal function
      of this protein. In order to investigate the relative contribution of these two
      opposite mechanisms, two theoretical approaches may be proposed: RNA interference
      (RNAi) and artificial prion engineering. In fact, RNAi techniques offer now an
      extremely exciting new tool for investigating the effects of gene silencing both
      in prion, and other neurological disorders. On the other hand, the gain-of-toxic
      function hypothesis might be definitely evaluated by creating an artificial prion
      choosing a protein target whose loss of function could be bypassed in the
      experimental set. In this paper the two aforementioned strategies are outlined,
      briefly discussing the consequent implications for TSE therapy.

PMID- 15488658
TI  - Periodic dip of lipidperoxidation in humans: a redox signal to synchronize
      peripheral circadian clocks?
AB  - The output generated by the endogenous circadian clock to control circadian
      functions and temporal organization in metazoans is unknown. Redox state
      perturbations generated by reactive oxygen species (ROS) and antioxidants are
      known to influence the expression of a number of genes and signal transduction
      pathways. Evidence has been recently provided that the reduced redox cofactors
      NAD and NADP both regulate clock gene activity in the suprachiasmatic nucleus
      (SCN) and are induced by it. Significant periodic variations of lipidperoxidation
      in human blood with a dip at 04.00 h have been previously reported. Such
      variations could be expected to alter the cellular redox state, thus possibly
      functioning as periodic redox signals from the master clock. To verify the
      existence of the mentioned variations the serum levels of malondialdehyde (MDA),
      a marker of lipidperoxidation, were monitored by High-Performance Liquid
      Chromatography in 39 healthy subjects at 3-h intervals over a 24-h period.
      Throughout the test period, only biological noise could be detected in all test
      persons. However, the normalized MDA levels at 03.00 h were significantly lower
      (p < 0.05 to < 0.00005) in 38 (97%) of the cases and showed a significantly lower
      standard deviation (p < 0.004) than at any of the other 3-h intervals, indicating
      a periodic dip of lipidperoxidation (PDL) in diurnal active subjects. We
      hypothesize that the PDL, on the basis of its time of appearance, its frequency
      and its potential influence on cellular redox state, represents a periodic
      systemic redox output of the SCN, in terms of a relatively short and sudden
      interruption of the daily oxidative noise. According to recent research, it could
      be the result of redox alterations induced by the SCN activity and at the same
      time the pathway by which the master clock resets and synchronizes peripheral
      oscillators to the light/dark cycle. Additionally, the antioxidative function of
      the pineal gland activity postulated elsewhere could play a part in generating
      the described phenomenon. The PDL could be useful as a circadian phase marker in
      research dealing with treatment of jet lag and other sleep disorders.

PMID- 15488659
TI  - Hypotheses on a germline origin of antibody diversity. Possible applications:
      improvement of the efficiency of immune response and autoimmune disease
      treatment.
AB  - In this paper, the antibody reaction is supposed to be due to the combination of
      a limited number of different antibodies against the epitopes of the antigen. In
      addition, the efficient part of the epitopes of proteins is assumed to be the
      size of dipeptides. The 400 different dipeptides would be distributed in two
      sets, those which are foreign to the host, against which would be directed
      antibodies, and those which are present in the proteins of the self, which would
      elicit no reaction. Each chain of the antibodies would recognise one aminoacid
      and 40 genes would be sufficient (20 for the light chains and 20 for the heavy
      chains) to code for the variable parts of the immunoglobulins against proteic
      antigens. With these hypotheses, the combination of antibodies against at least
      four different epitopes of the size of dipeptides can account for the main
      characteristics of the antibody reaction: response against any foreign proteic
      antigen and specificity. In fact, the epitopes have been found to be larger than
      dipeptides, several additional aminoacids are involved in the antibody-binding
      sites. Somatic mutations and VDJ recombinations are selected to give the maximal
      affinity for the antigens. However, these mechanisms have not been shown to
      create different specificities from the same V genes. Moreover, the phenomenon of
      heteroclisis and the decrease, due to mutations, of antigen-binding capacity of
      antibodies, sometimes observed, are better explained by the model proposed here
      than by the classical theory. The modification of the epitope subset of the self,
      by intrathymic injection of antibodies against particular pathogens, is proposed
      to improve the immune response when microorganisms develop immune escape
      mechanisms. On the other hand, in the case of autoimmune diseases, the
      displacement of autoantibodies against self-epitopes could be carried out by the
      injection into the thymus of specific anti-idiotypic antibodies.

PMID- 15488660
TI  - Molecular mimicry of ACTH in SARS - implications for corticosteroid treatment and
      prophylaxis.
AB  - For a virus to survive and replicate in an organism, it must employ strategies to
      evade and misdirect the host's immune response. There is compelling evidence that
      the primary immunoevasive strategy utilized by the SARS virus, like influenza, is
      to inhibit its host's corticosteroid stress response. This is accomplished by
      viral expression of amino acid sequences that are molecular mimics of the host's
      adrenocorticotropin hormone (ACTH). When the host produces antibodies against
      these viral antigens, the antibodies also bind to the host's own ACTH, which
      limits the host's stress response by interfering with ACTH's ability to stimulate
      the secretion of corticosteroids. This inadequate corticosteroid response
      provokes symptoms as a result of a relative adrenocortical insufficiency.
      Treatment with corticosteroids can relieve the patient's symptoms of
      adrenocortical insufficiency and give them the corticosteroid levels needed to
      fight their infection. Similarly, by taking moderate daily doses of
      corticosteroids as a prophylactic, it may be possible to avoid clinical infection
      with SARS. If SARS's ACTH mimic strategy never has an opportunity to get started,
      SARS's ability to evade its host's immune system while its viral load is low will
      be significantly impaired. In this article, amino acid sequences from the SARS
      and influenza viruses representing likely homology to human ACTH are identified.
      Evidence demonstrating that ACTH autoantibodies are produced during influenza
      infection is also presented. Early treatment with corticosteroids should lower
      the dose necessary to counteract SARS's ACTH autoantibody mechanism. If
      corticosteroid treatment is delayed until inflammatory cytokine levels are
      causing serious injury, only high doses of corticosteroids are likely to be
      effective.

PMID- 15488661
TI  - Suppression of bacterial biofilm formation by iron limitation.
AB  - The concentration of iron that permits bacterial differentiation generally
      differs from that needed for vegetative cell growth. An undesirable manifestation
      of differentiation is biofilm formation. The process in some, but not all,
      bacterial systems requires a higher level of iron than is needed for growth and
      it is suppressed by specific iron chelators. Human transferrin and lactoferrin,
      as well as at least six low molecular mass iron chelators, are now available for
      possible screening and clinical development as inhibitors of bacterial biofilm
      formation.

PMID- 15488662
TI  - How hematopoietic stem cells know and act in cardiac microenvironment for stem
      cell plasticity? Impact of local renin-angiotensin systems.
AB  - Bone marrow-derived hematopoietic stem cells (HSC) can exhibit tremendous
      differentiation activity in numerous non-hematopoietic organs. This enigmatic
      process is called as 'stem cell plasticity' (SCP). HSC may promote structural and
      functional repair in several organs such as heart, liver, brain, and skeletal
      muscle via the SCP. The differentiation capacity of HSC is dependent on the
      specific signals present in the local tissue microenvironment. Those specific
      molecular signals required for the interactions of HSC and host tissues are
      currently unknown. The aim of this report is to propose a hypothesis on how HSC
      reach, recognize, and function in cardiac tissues in the context of SCP. Locally
      signaling cardiac microenvironment is essential for the seeding, expansion, and
      'cardiomyocyte differentiation' of the HSC in the heart. Our hypothesis is that
      the receptors, ligands, and signaling pathways of the tissue renin-angiotensin
      system (RAS) serve as the link between HSC and local cardiac microenvironment in
      SCP. The RAS is considered as a 'tissue-based system' exhibiting paracrine
      functions within many organs. The presence of local hematopoietic bone marrow RAS
      and local cardiac RAS have been suggested. Both local tissue RASs share similar
      angiotensin peptide-signaling pathways such as JAK-STAT and mitogen-activated
      protein kinases. HSC have angiotensin type I (AT1a) receptors for the binding of
      angiotensin II, the active component of the RAS. Binding of angiotensin II to
      AT1a can increase hematopoietic progenitor cell proliferation. Local cardiac RAS
      has critical (patho)biological functions in the cardiomyocyte survival, renewal,
      and growth, as well as in cardiac remodeling. Therefore, the components of the
      local cardiac RAS and hematopoietic RAS could interact with each other during the
      SCP through myocardial tissue repair. Activation of the local myocardial RAS
      after injury may be related to homing and engraftment of the HSC to the cardiac
      tissue. Regenerating myocardial tissue may exert regulatory functions on
      circulating or resident HSC via the locally active RAS. Understanding the exact
      molecular basis of SCP in relation to local tissue RAS could offer new frontiers
      in the better management of ischemic cardiac diseases.

PMID- 15488663
TI  - Is there a causative role for tetanus toxoid vaccination in the development of
      allergy-like symptoms and in the increasing prevalence of atopic diseases?
AB  - Allergic diseases are a worldwide health problem. They mainly affect people
      living in developed countries where an increasing prevalence of allergy symptoms
      has been recorded in the last 20-30 years. The cause of this increase is still
      disputed, and, among others, the "hygiene hypothesis" supported the concept that
      relevant changes in lifestyle could have a relationship with the phenomenon. More
      recently the recorded parallel increase in autoimmune diseases has suggested to
      consider the "hygiene hypothesis" as a cause of a more general disregulation of
      the immune system leading to both allergy and to autoimmunity. Here are reported
      a series of observations, evidence, and data from the literature leading to a
      different hypothesis. The key points are: (1) the presence of two subsets of
      patients having allergy symptoms based on an IgE-mediated mechanism or not; (2)
      the positive results obtained with the autologous serum skin test in either
      cutaneous or respiratory affected subjects, mainly in children and adult females;
      (3) the presence of IgG autoantibodies against the alpha-chain of the high
      affinity IgE receptor (FcepsilonRIalpha) in non-IgE-mediated urticaria and even
      in respiratory subjects; (4) the cross-reactivity between epitopes of the tetanus
      toxoid molecule and the FcepsilonRIalpha detected by means of an alpha-chain
      affinity purified IgG fraction; (5) the positive skin reactivity obtained using
      IgG anti-tetanus toxoid preparations in allergic and non-allergic volunteers. The
      presence of IgG autoantibodies actively generated by the population-based
      vaccination with tetanus toxoid could induce both mediator release from activated
      mast cell and Th2 cytokine production early in life. There are epidemiological
      evidences that tetanus toxoid vaccination could be linked with an increased
      tendency to have allergy symptoms. The different epidemiological distribution of
      non-IgE-mediated symptoms, mainly affecting young infants would be in agreement
      with the present hypothesis. The prevalent mother-to-child relationship in terms
      of risk for allergy symptoms could be explained with the trans-placenta transfer
      of IgG. A similar transfer could also take place through the mother milk during
      breast feeding. It may thus be hypothesized that the increased prevalence of
      allergic diseases could be caused by the generalized tetanus toxoid immunization
      procedure, progressively extended to most of the countries worldwide in the last
      30-40 years. Both the induction of non-IgE-mediated symptoms caused by the mast
      cell activation via the anti-FcepsilonRIalpha IgG and the long lasting Th2
      inflammation of affected tissues would be the inducing mechanisms. This
      hypothesis would re-configure part of the allergic diseases as a Th2 phenotypic
      expression of an autoimmune disease.

PMID- 15488664
TI  - A proposal regarding the biology of memory: participation of intracrine peptide
      networks.
AB  - Although progress has recently been made in defining its neurobiological
      underpinnings, memory remains an incompletely understood process. Here it is
      proposed that intracrine peptide action plays a role in memory and therefore in
      consciousness. Intracrine function is the intracellular action of a peptide
      either in its cell of synthesis or in target cells following internalization.
      Intracrine functionality has been associated with growth factors, transcription
      factors, and enzymes. Some intracrines have been shown to modify their own
      synthesis, the synthesis of components of their signaling cascades, and/or the
      synthesis of other intracrines, making it likely that these factors participate
      in peptinergic regulatory loops/networks. Moreover, some intracrines can affect
      cellular ion flows over short time periods, while stimulating protein synthesis
      and growth over longer periods. Intracrines have been reported in the brain (for
      example, angiotensin, brain derived neurotrophic factor, reelin, and fibroblast
      growth factor 2) and it is here suggested that intracrine expression/action
      occurs commonly in the nervous system and, in particular, in the cerebral cortex.
      This intracrine action leads to the formation of long-lived intra- and
      intercellular intracrine feed back loops. The intracrine networks thus formed
      participate in producing both short and long term synaptic potentiation; the
      former effect is primarily related to intracrine effects on ion flows, the latter
      to intracrine directed protein synthesis. In addition, intracrine networks
      provide a previously unappreciated dynamic substrate for the integration of
      information and ultimately for the formation of the associations that underlay
      consciousness.

PMID- 15488665
TI  - Can the human brain do quantum computing?
AB  - The electrical membrane properties have been the key issues in the understanding
      of the cerebral physiology for more than almost two centuries. But, molecular
      neurobiology has now discovered that biochemical transactions play an important
      role in neuronal computations. Quantum computing (QC) is becoming a reality both
      from the theoretical point of view as well as from practical applications.
      Quantum mechanics is the most accurate description at atomic level and it lies
      behind all chemistry that provides the basis for biology ... maybe the magic of
      entanglement is also crucial for life. The purpose of the present paper is to
      discuss the dendrite spine as a quantum computing device, taking into account
      what is known about the physiology of the glutamate receptors and the cascade of
      biochemical transactions triggered by the glutamate binding to these receptors.

PMID- 15488666
TI  - The emergence of consciousness.
AB  - Consciousness is the primary aspect of our lives. The true nature of
      consciousness (its subjectivity and intentionality) has resisted scientific
      explanation for centuries. This has important implications for scientific
      understanding and progress, as well as for the study and treatment of medical
      disorders, most of which involve some element of consciousness. In this paper, a
      basic nonlinear emergent mechanism (responsible for a large number of natural
      phenomena) is described. This mechanism produces nonlinear explicit states that
      have all the same properties as consciousness and hence the two may be identical.
      This mechanism might be applied to explain the generation of human consciousness.
      There is an intimate relation between consciousness and voluntary (by choice,
      free will) new or novel intentional (goal-directed) action-any action or action
      sequence (whether muscular movement, ocular movement, speech, thought, emotion)
      created anew by choice to achieve some goal. Consciousness always accompanies the
      production of such action (conscious action). Thus, a physical mechanism
      utilizing the basic type of nonlinear emergence (positive feedback between
      release and dissipation events, inhibition, formation of an explicit state,
      effects produced in other systems) was suggested for the production of voluntary
      new or novel intentional action from perception. This mechanism agrees with a
      large amount of research data for the production of such action. The nonlinear
      explicit states produced by the nonlinear mechanism from perception appear to
      have identical properties to human consciousness. Hence consciousness is natural,
      material, and functional; not something mysterious, nonmaterial, and
      epiphenomenal as has often been portrayed. It has evolved in humans for the
      creation of adaptive action. This means that consciousness can be explained and
      studied scientifically and medical disorders involving consciousness treatable by
      basic clinical treatment (psychiatric, medicinal, psychological). This theory
      also provides possibilities for the explanation of many puzzling questions: What
      brain structures are involved in producing consciousness. How these effects may
      be produced, manipulated, or complemented. That other animals may be conscious.
      That machines may be built to be conscious. That certain natural systems may have
      a degree of consciousness. That paranormal phenomena may be explained via these
      principles.

PMID- 15488667
TI  - Did an epidemic of tularemia in Ancient Egypt affect the course of world history?
AB  - The dynamics of the spreading, and the identity of a virulent epidemic, similar
      to bubonic plague or typhus, which hit Ancient Egypt in the middle of the Bronze
      Age, are hereby presented. Documented in medical papyri as well as archaeological
      findings, and re-echoed in biblical texts, a plague entered Egypt's main harbor,
      Avaris, around 1715 BC. As a result, the country was severely weakened at a time
      when it was already facing serious sociopolitical issues: crumbling central
      government, immigration, foreign influence, and the rise in power of the army and
      of warlords. The Hebrews, one of the ethnic groups within the Avaris area,
      appeared immune amidst the devastation of the plague. This immunity was key to
      identify the etiological agent of the epidemic: Francisella tularensis, the Gram
      negative bacterium passed by ticks, and that causes tularemia. The disease
      manifests itself as either an ulceroglandular or a typhoid syndrome, accounting
      for its similarity with bubonic plague and typhus. Cellular immunity provides the
      main defense against F. tularensis, and is achieved through continuous contact
      with avirulent strains of the bacterium. Urban dwellers of Avaris, who had a
      limited contact to animals, would have been defenseless against the virulent
      strains, unlike the Hebrews, who lived off sheep and other animals. Attempting to
      consolidate Egypt's central government in the aftermath of the tularemia
      epidemic, led among others to the internment of the Hebrews in labor camps. The
      repressive measures against the Hebrews left traces in the subsequent
      archaeological layer (stratum F) at Avaris. As a corollary, the enslavement would
      set the stage for the exodus of the Hebrew community from Egypt at a later time.

PMID- 15488668
TI  - The Eyam plague revisited: did the village isolation change transmission from
      fleas to pulmonary?
AB  - Back in the 17th century the Derbyshire village of Eyam fell victim to the Black
      Death, which is thought to have arrived from London in some old clothes brought
      by a travelling tailor. The village population was 350 at the commencement of
      plague, of which only 83 survived. Led by the church leaders, the village
      community realized that the whole surrounding region was at risk from the
      epidemic, and therefore decided to seal themselves off from the other surrounding
      villages. In the first 275 days of the outbreak, transmission was predominantly
      from infected fleas to susceptible humans. From then onward, mortality sharply
      increased, which indicates a changing in transmission pattern. We hypothesize
      that the confinement facilitated the spread of the infection by increasing the
      contact rate through direct transmission among humans. This would be more
      consistent with pulmonary plague, a deadlier form of the disease. In order to
      test the above hypothesis we designed a mathematical model for plague dynamics,
      incorporating both the indirect (fleas-rats-humans) and direct (human-to-human)
      transmissions of the infection. Our results show remarkable agreement between
      data and the model, lending support to our hypotheses. The Eyam plague episode is
      celebrated as a remarkable act of collective self-sacrifice. However, to the best
      of our knowledge, there were no evidence before that the confinement actually
      increased the burden payed by the commoners. In the light of our results, it can
      be said that the hypothesis that confinement facilitated the spread of the
      infection by increasing the contact rate through direct transmission is
      plausible.

PMID- 15488669
TI  - Alcoholism, depression and obesity.

PMID- 15488670
TI  - Nerve growth factor, follicle stimulating hormone receptor and epithelial ovarian
      cancer.

PMID- 15488671
TI  - Gulf war syndrome and sand fly saliva.

PMID- 15488672
TI  - The possible substrate inhibition of epidermal phenylalanine hydroxylase in
      vitiligo: a new pathogenetic approach.

PMID- 15488673
TI  - From brain science to brain based medicine.

PMID- 15488674
TI  - Spectroscopic features of radiolytic intermediates induced in gamma irradiated
      sulfatiazole: an ESR study.
AB  - Sulfonamides are used as active ingredients in different drugs to treat
      infections caused by bacteria. Sulfatiazole (STZ) is one of the commonly used
      sulfonamides as antibacterial agent in drugs, which constitute potential
      candidates for radiosterilization. However, the crucial point in this respect is
      to monitor the amount and characteristic features of the radiolytic intermediates
      produced after irradiation. Electron spin resonance (ESR) spectroscopy is
      extensively used for this purpose due to its high sensitivity toward
      intermediates exhibiting radicalic nature. Thus, the aim of the present work is
      to investigate the spectroscopic and kinetic features of the species having
      unpaired electrons induced in gamma irradiated STZ at room and different
      temperatures in the dose range of 5-50kGy using ESR spectroscopy. Spectra of
      irradiated STZ consisted of many resonance peaks in the studied dose and
      temperature ranges. Heights of the peaks measured with respect to the base line
      were used to monitor microwave, temperature, time-dependent features of the
      radical species contributing to the experimental ESR spectra. Four tentative
      species of different spectroscopic and structural features assigned as A, B, C
      and D were found well explaining the experimental ESR spectra of gamma irradiated
      STZ. Comparison between the principal IR bands of unirradiated and gamma
      irradiated samples showed no detectable changes and appearance of new bands.

PMID- 15488675
TI  - Polymorphism of pindolol, 1-(1H-indol-4-yloxyl)-3-isopropylamino-propan-2-ol.
AB  - Crystallization of pindolol from the melt was studied by differential scanning
      calorimetry (DSC) and polarized light thermomicroscopy (PLTM) in order to
      discriminate the polymorphic forms obtained by this method. The crystallization
      process originates one exothermic signal localized in two different well-defined
      temperature ranges. Fusion gives rise to overlapped curves, which were analysed
      by peak-fitting. The polymorphs were identified as the clusters formed with the
      values obtained for T(peak) of the component curves. Three polymorphic forms were
      exhibited by pindolol crystallized from the melt. Commercial pindolol presents
      only two of these forms.

PMID- 15488676
TI  - Liposome formulation of poorly water soluble drugs: optimisation of drug loading
      and ESEM analysis of stability.
AB  - Liposomes due to their biphasic characteristic and diversity in design,
      composition and construction, offer a dynamic and adaptable technology for
      enhancing drug solubility. Starting with equimolar egg-phosphatidylcholine
      (PC)/cholesterol liposomes, the influence of the liposomal composition and
      surface charge on the incorporation and retention of a model poorly water soluble
      drug, ibuprofen was investigated. Both the incorporation and the release of
      ibuprofen were influenced by the lipid composition of the multi-lamellar vesicles
      (MLV) with inclusion of the long alkyl chain lipid (dilignoceroyl
      phosphatidylcholine (C24PC)) resulting in enhanced ibuprofen incorporation
      efficiency and retention. The cholesterol content of the liposome bilayer was
      also shown to influence ibuprofen incorporation with maximum ibuprofen
      incorporation efficiency achieved when 4 micromol of cholesterol was present in
      the MLV formulation. Addition of anionic lipid dicetylphosphate (DCP) reduced
      ibuprofen drug loading presumably due to electrostatic repulsive forces between
      the carboxyl group of ibuprofen and the anionic head-group of DCP. In contrast,
      the addition of 2 micromol of the cationic lipid stearylamine (SA) to the
      liposome formulation (PC:Chol - 16 micromol:4 micromol) increased ibuprofen
      incorporation efficiency by approximately 8%. However further increases of the SA
      content to 4 micromol and above reduced incorporation by almost 50% compared to
      liposome formulations excluding the cationic lipid. Environmental scanning
      electron microscopy (ESEM) was used to dynamically follow the changes in liposome
      morphology during dehydration to provide an alternative assay of liposome
      stability. ESEM analysis clearly demonstrated that ibuprofen incorporation
      improved the stability of PC:Chol liposomes as evidenced by an increased
      resistance to coalescence during dehydration. These finding suggest a positive
      interaction between amphiphilic ibuprofen molecules and the bilayer structure of
      the liposome.

PMID- 15488677
TI  - Macromolecular prodrugs XI. Synthesis and characterization of polymer-estradiol
      conjugate.
AB  - Estradiol-3-benzoate (EB), an ester derivative of the main oestrogen hormone
      estradiol, was chemically modified and bound to poly(alpha,beta-(N-2-hydroxyethyl
      DL-aspartamide))-poly(alpha,beta-(N-2-aminoethyl-DL-aspartamide)) copolymer
      (PAHA). EB was first converted to estradiol-3-benzoate-17-(benzotriazole-1
      carboxylate), which readily reacted with amino groups in PAHA affording the
      polymer-drug conjugate PAHA-EB. In PAHA-EB estradiol moiety was covalently bound
      to the polymeric carrier by carbamate linkage, through non-toxic ethylenediamine
      spacer. The synthesized compound is a potential hydrosoluble estradiol prodrug.

PMID- 15488679
TI  - Investigations into the use of pregelatinised starch to develop powder-filled
      hard capsules.
AB  - The use of pregelatinised starch in tamp filling of hard capsules with powder
      formulations containing a low-solubility drug (theophylline anhydrous) with very
      poor powder flow and stickiness to metal surfaces was investigated. Twenty-one
      mixtures containing the drug, pregelatinised starch, lactose monohydrate and
      magnesium stearate were produced, with their quantitative composition based on a
      central composite design. These mixtures were filled into hard capsules using an
      instrumented tamp-filling machine. Seven different compression settings ranging
      from "no" to "firm" compression were employed, and the tamping force was recorded
      on stations 3 and 4. It was found that the use of pregelatinised starch as an
      excipient in the manufacture of powder-filled hard capsules could be beneficial
      in terms of reducing the coefficient of fill weight variability. To improve drug
      dissolution of poorly soluble drugs, larger amounts of this excipient were
      required, and the maximum capsule fill weight that could be achieved was slightly
      reduced at the same time.

PMID- 15488678
TI  - Effects of HPE-101, a skin penetration enhancer, on human erythrocyte membranes.
AB  - The primary aim of this study was to investigate the skin permeation-enhancing
      mechanism of HPE-101 using erythrocyte ghost cells prepared from human whole
      blood as a biomembrane model. The extent of hemolysis of erythrocytes induced by
      HPE-101 was measured using a spectrophotometer at 540nm. The effect of HPE-101 on
      lipid fluidity was examined by observing the change of intramolecular excimer
      formation and fluorescence polarization using an intramolecular probe (1,3
      bis(pyrene) propane) and a lipid probe (1,6-diphenyl 1,3,5-hexatriene),
      respectively. Hemolysis of erythrocytes was observed at 0.01mM and completed at
      1.0mM of HPE-101. The fluorescence polarization of the ghost membrane decreased
      with the addition of HPE-101, whereas the intramolecular excimer formation
      increased. HPE-101 thus enhanced the rotational mobility and the lateral
      diffusion, thereby decreasing the microviscosity of ghost membranes, implying
      that HPE-101 increases the lipid fluidity of ghost membranes. Therefore, HPE-101
      seems to cause an increase in fluidity of the lipid bilayers in the stratum
      corneum of the skin, resulting in the reduction of diffusion resistance.

PMID- 15488680
TI  - Process characterisation, optimisation and validation of production of
      diacetylmorphine/caffeine sachets: a design of experiments approach.
AB  - Powder filled sachets containing a 3:1 (w/w) powder mixture of diacetylmorphine
      base and caffeine anhydrate were developed as a dosage form for smokable heroin
      used for the treatment of chronic, treatment-resistant heroin addicts. The powder
      mixture was filled into sachets using a micro dose auger filler machine. The goal
      of this study was to identify the most important process variables that influence
      precision of dosing. Five variables were tested: auger speed, agitator speed,
      hopper fill level, dose interval, and dose. An experimental design was used to
      study the effects of each of these variables, including possible non-linear and
      interaction effects. A 9-term regression model was constructed, explaining 94% of
      the observed variation in dose weight variation coefficient. Dose, agitator speed
      and hopper fill level were the most important variables. The regression model was
      used to identify optimal settings of the variables for four sachet doses intended
      for routine manufacture. The results of four test batches manufactured with these
      optimised settings showed that accurate (accuracy: 99.0-101.0%) and precise (CV:
      3.2-5.3%) filling of diacetylmorphine/caffeine sachets is possible using the
      micro dose auger filler machine.

PMID- 15488681
TI  - Glucose-targeted niosomes deliver vasoactive intestinal peptide (VIP) to the
      brain.
AB  - The aim of this study was to evaluate glucose-bearing niosomes as a brain
      targeted delivery system for the vasoactive intestinal peptide (VIP). To this
      end, VIP/125I-VIP-loaded glucose-bearing niosomes were intravenously injected to
      mice. Brain uptake was determined by measuring the radioactivity of 125I-labeled
      VIP using gamma-counting, after intravenous administration of VIP in solution or
      encapsulated in glucose-bearing niosomes or in control niosomes. VIP integrity
      was assessed by reversed-phase HPLC analysis of brain extracts. Distribution of
      125I-VIP derived radioactivity was examined from serial brain slices. HPLC
      analysis confirmed the presence of intact VIP in brain after administration of
      VIP-loaded niosomes, but not after administration of VIP solution. Encapsulation
      within glucose-bearing niosomes mainly allowed a significantly higher VIP brain
      uptake compared to control niosomes (up to 86%, 5min after treatment). Brain
      distribution of intact VIP after injection of glucose-bearing niosomes, indicated
      that radioactivity was preferentially located in the posterior and the anterior
      parts of the brain, whereas it was homogeneously distributed in the whole brain
      after the administration of control vesicles. In conclusion, this novel vesicular
      formulation of VIP delivers intact VIP to particular brain regions in mice.
      Glucose-bearing vesicles might be therefore a novel tool to deliver drugs across
      the blood-brain barrier (BBB).

PMID- 15488682
TI  - Preparation and characterisation of poly(vinyl alcohol)/cyclodextrin microspheres
      as matrix for inclusion and separation of drugs.
AB  - Poly(vinyl alcohol) (PVA) microspheres containing cyclodextrin (CD) were obtained
      by chemical cross-linking with glutaraldehyde of an acidified mixture solution of
      PVA and alpha-, beta- or gamma-CD. The amount of linked CD in microspheres,
      estimated by tetrazolium blue method, decreases in the order beta- > gamma- >
      alpha-CD. The dimensions of PVA/gamma-CD microspheres are much higher than those
      of PVA/alpha- and beta-CD. The cross-linking density of microspheres was
      estimated by the amount of iodine retained by the polymer matrix. The pore size
      as well as the porous volume of PVA/CD microspheres decrease significantly on
      increasing the amount of glutaraldehyde, but are enough large to permit the
      access of drugs to the CD cavity. In order to test the PVA/CD microsphere
      inclusion ability, the microspheres were packed in a glass column and the liquid
      chromatographic behaviour by isocratic elution of different drugs or typical
      organic compounds, taken as model drugs, was investigated.

PMID- 15488683
TI  - The effect of vehicle on physical properties and aerosolisation behaviour of
      disodium cromoglycate microparticles spray dried alone or with L-leucine.
AB  - The aim of this study was to improve the aerosolisation behaviour of disodium
      cromogycate (DSCG), using spray drying technique. The effect of vehicle on the
      drug particle properties was investigated. L-leucine was selected as a natural
      antiadherent amino acid to improve the deagglomeration of DSCG particles. Spray
      dried samples of DSCG alone or with L-leucine were prepared from water and
      ethanol under the same conditions. The powder properties of the samples were
      examined by laser diffraction, helium densitometer, X-ray diffraction,
      differential scanning calorimetry and thermogravimetric analysis. The in vitro
      deposition was determined, using an Andersen cascade impactor with a Spinhaler at
      a flow rate of 60 l/min. An amorphous form of the drug was obtained when water
      was used. However, crystal transformation of original DSCG in the presence of
      ethanol during spray drying resulted in production of elongated particles. These
      particles exhibited improved aerodynamic properties, compared to the amorphous
      and commercial materials. Significant differences in fine particle fraction were
      observed using the two vehicles. Co-spray drying of DSCG and L-leucine improved
      the deposition profiles of the drug. These results indicated that the change in
      crystal structure of DSCG during spray drying process was susceptible to the
      nature of the vehicle. A crystalline form of DSCG with good aerodynamic
      properties was achieved during spray drying process. In addition, the processing
      of DSCG with L-leucine in a single step using ethanol resulted in an improvement
      in dispersion properties of the drug particles.

PMID- 15488684
TI  - Preparation and in vitro characterization of self-nanoemulsified drug delivery
      system (SNEDDS) of all-trans-retinol acetate.
AB  - PURPOSE: To prepare a self-nanoemulsified drug delivery system (SNEDDS) of all
      trans-retinol acetate, with enhanced dissolution and better chance of oral
      absorption. METHOD: All-trans-retinol acetate SNEDDS was prepared using different
      concentrations of soybean oil (solvent) Cremophor EL (surfactant) and Capmul MCM
      C8 (co-surfactant). Particle size and turbidity of the SNEDDS were determined
      after adding water to the oily solution. Dissolution profile of SNEDDS filled in
      hydroxyl propyl methyl cellulose (HPMC) capsules was determined by using water in
      USP apparatus 2. Ternary phase diagrams were constructed to identify the self
      nanoemulsified region. The SNEDDS were evaluated by the visual observation,
      turbidity in nephrometric turbidity units (NTU), mean particle size (microm) and
      Fourier transformed-infrared spectroscopy (FT-IR). SNEDDS were thermally
      characterized using differential scanning calorimetry (DSC) to ensure the
      compatibility of the SNEDDS ingredient. RESULTS: From the data obtained in this
      work, it was clear that surfactant to co-surfactant ratio has the main impact on
      the physical characteristics of the emulsion formed. The optimum surfactant to co
      surfactant ratio was found to be 2:1 (37.5-50% for Cremophor EL, and 18.75-25%
      for Capmul MCM-C8). With this ratio, the resultant nanoemulsions obtained have a
      particle size range of 0.103-0.051 microm, turbidity range of 18.12-2.18 NTU and
      t30 values (cumulative% all-trans-retinol acetate dissolved in 30 min) of 90.42
      99.5. Also the thermograms obtained from DSC experiments showed that there is no
      incompatibility or interaction between the SNEDDS ingredients (soybean oil,
      Cremophor EL, and Capmul MCM-C8) and all-trans-retinol acetate. CONCLUSION: The
      present study revealed that the self-nanoemulsified drug delivery system of all
      trans-retinol acetate increased its dissolution rate and has the potential to
      enhance its bioavailability without interaction or incompatibility between the
      ingredients.

PMID- 15488685
TI  - Polynorbornene polycationic polymers as gene transfer agents. Influence of the
      counterion for in vitro transfection.
AB  - Polycationic derivatives of polynorbornene with different non-cytotoxic
      counterions, have been prepared by organometallic polymerization of
      methyleneammonium norbornene and subsequent exchange of the counterion. In this
      paper the effect of the counterion on the polycationic polymer binding onto
      plasmid DNA was studied via different ethidium bromide assays, heparin
      displacement and protection against degradation by DNAse. According to the nature
      of the counterions and consequently the size of the polymer particles, their
      complexation with the DNA led to aggregates with variable binding affinity for
      the plasmid. The relative transfection efficiency of each polyplex was compared,
      on the basis of reporter gene expression, in cells in culture. The nature of the
      counterion was seen to affect gene delivery. The order of transfection efficiency
      of the counterions studied at equivalent charge ratios (NH3+/PO4-) is
      lactobionate, acetate, chloride. The results obtained with the polynorbornene
      methyleneammonium lactobionate and acetate are particularly encouraging.

PMID- 15488686
TI  - The role of biopharmaceutics in the development of a clinical nanoparticle
      formulation of MK-0869: a Beagle dog model predicts improved bioavailability and
      diminished food effect on absorption in human.
AB  - MK-0869 (aprepitant), a potent substance P antagonist, is the active ingredient
      of EMEND which has recently been approved by the FDA for the prevention of
      chemotherapy-induced nausea and vomiting. Early clinical tablet formulations of
      MK-0869 showed significant food effects on absorption, suggesting that
      formulation could have a significant role in improving bioavailability. A Beagle
      dog model was developed in an effort to guide novel formulation development.
      Using the suspension of the micronized bulk drug used for the tablet
      formulations, the food effect on absorption was confirmed in the dog at a similar
      magnitude to that observed in humans. Further dog studies demonstrated a clear
      correlation between particle size and in vivo exposures, with the nanoparticle
      (NanoCrystal) colloidal dispersion formulation providing the highest exposure,
      suggesting dissolution-limited absorption. The NanoCrystal dispersion also
      eliminated the food effect on oral absorption in the dog at a dose of 2mg/kg.
      Regional absorption studies using triport dogs indicated that the absorption of
      MK-0869 was limited to the upper gastrointestinal tract. These results provided
      strong evidence that the large increase in surface areas of the drug
      nanoparticles could overcome the narrow absorption window and lead to rapid in
      vivo dissolution, fast absorption, and increased bioavailability. In addition,
      the dog model was used for optimizing formulation processes in which the
      nanoparticles were incorporated into solid dosage forms, and for selecting
      excipients to effectively re-disperse the nanoparticles from the dosage units.
      The human pharmacokinetic data using the nanoparticle formulation showed
      excellent correlations with those generated in the dog.

PMID- 15488688
TI  - Observational research in rheumatic disorders.
AB  - Observational research plays an important role in science. Much of human
      knowledge, including health knowledge, comes from observations, not experiments.
      Within medicine, observational studies cover a wide scope that ranges from case
      reports and case series, to descriptive studies, to analytic observational
      studies for causal questions. These studies often are complementary; each
      provides a piece of information that can be synthesized into a description and
      analysis of a health problem in a way that tests hypotheses and advances medical
      science and has the potential to lead to interventions that can improve health
      and quality of life. This article reviews the scope of observational studies,
      principles of causal inference in observational studies, and various types of
      observational studies with a focus of their applications in rheumatic disorders.

PMID- 15488689
TI  - Clinical trials in rheumatic diseases: designs and limitations.
AB  - Randomized controlled clinical trials provide the best method to distinguish a
      drug from placebo without the inevitable selection biases that are seen in
      standard clinical care. This article reviews designs and limitations of clinical
      trials that are used in rheumatic diseases. The primary design in clinical trials
      is a parallel, in which patients are randomized in parallel to different
      therapies at different dosages or placebo. In recent years, other designs have
      been used increasingly, including "step-up," "step-down," and "cross-over"
      designs. Limitations of clinical trials in chronic diseases include a short time
      frame versus the long duration of disease, inclusion and exclusion criteria, use
      of surrogate markers that may not represent clinically relevant markers,
      statistical significance does not necessarily indicate clinical significance
      necessarily, and the fact that a control group does not assure the absence of
      bias. Therefore, long-term databases are needed to supplement clinical trials in
      analyzing results of therapy for rheumatoid arthritis.

PMID- 15488690
TI  - Quantitative measures and indices to assess rheumatoid arthritis in clinical
      trials and clinical care.
AB  - Modern medical care has been advanced, in large part, by quantitative measures
      that provide single, easily-assessed end points for clinical trials, clinical
      research, or clinical care (eg, blood pressure, serum cholesterol). In rheumatoid
      arthritis, several types of quantitative measures are used to assess patient
      status, including formal joint counts; radiographic scores; laboratory tests;
      patient self-report questionnaire measures of physical function, pain, global
      status, morning stiffness, and fatigue; as well as physical measures of
      functional status. Each of these measures is effective to document changes of
      status with treatment in groups of patients; however, no single measure can serve
      as a "gold standard" to document changes in each individual patient. Therefore,
      the measures have been combined into pooled indices that can be applied to
      individual patients in clinical research and clinical care.

PMID- 15488691
TI  - Data collection, maintenance, and analysis for rheumatic disease research.
AB  - With the increasing availability of inexpensive, powerful computers and software,
      clinicians and academics are constructing or thinking about constructing
      rheumatic disease outcomes databases. This article describes concepts, methods,
      and problems in database construction and analysis based on the experience of the
      US National Data Bank for Rheumatic Diseases.

PMID- 15488692
TI  - Rheumatoid arthritis databases.
AB  - Rheumatoid arthritis (RA) registers and databases serve as data storage for
      longitudinal observational studies. This article describes selected computerized
      RA databases from the United States and Europe and focuses on their novel
      observations concerning long-term outcomes of RA.

PMID- 15488693
TI  - Epidemiologic studies for osteoarthritis: new versus conventional study design
      approaches.
AB  - This article discusses epidemiologic study designs for osteoarthritis and why
      traditional designs are outmoded. It reviews the design of new studies, the
      Osteoarthritis Initiative and Multicenter Ostroarthritis Study.

PMID- 15488694
TI  - Prospective cohorts and rheumatic disease research.
AB  - Many large, prospective cohort studies originally were established to study
      common major medical conditions, including heart disease and cancer. These
      cohorts have provided important health information for decades (eg, the link
      between smoking and lung cancer). More recently, some of these cohorts also have
      provided excellent vehicles for addressing important study questions of common
      rheumatic disorders. An increasing number of important observational studies has
      been published or are being conducted based on these cohorts; the role of these
      data sources in rheumatic disease research are likely to grow in the future. This
      article intends to put these prospective cohort studies together to enhance the
      understanding of their usefulness in studying rheumatic disorders among
      investigators and readers. We summarize those cohorts with their published
      examples of rheumatic disease research.

PMID- 15488695
TI  - Rochester Epidemiology Project: a unique resource for research in the rheumatic
      diseases.
AB  - Olmsted County, Minnesota is one of the few places in the world to conduct
      comprehensive population-based studies of disease etiology, natural history, and
      outcomes because of a unique resource, the Rochester Epidemiology Project (REP).
      This article describes the REP and highlights its research capabilities in the
      context of the rheumatic diseases.

PMID- 15488696
TI  - Pharmacoepidemiology and rheumatic disorders.
AB  - This article reviews the application of pharmacoepidemiology in the evaluation of
      drugs that are used commonly for rheumatic disorders. Data sources and
      methodology considerations for these studies are highlighted. The topics that are
      covered included the safety evaluation of nonsteroidal ant-inflammatory drugs,
      adverse pregnancy outcomes of pharmaceutical agents, gastroduodenal safety of
      alendronate, long-term beneficial effects of methotrexate for rheumatoid
      arthritis, and drug use study.

PMID- 15488697
TI  - National databases and rheumatology research I: longitudinal databases in
      Scandinavia.
AB  - Nationwide population-based longitudinal databases provide excellent resources
      for medical research in Scandinavia. These include the Population Registry, the
      Cancer Registry, the Cause of Death Registry, the Hospital Discharge Registry,
      and other registers, and are linkable to each other by the personal
      identification code. The registers have long historical backgrounds, and are
      regulated strictly by law. This article describes features of the national
      databases and provides some examples of rheumatology research that use these
      databases.

PMID- 15488698
TI  - National databases and rheumatology research II: the National Health and
      Nutrition Examination Surveys.
AB  - Three National Health and Nutrition Examination Surveys were conducted in the
      United States between 1971 and 1994 to provide data on the nutritional and health
      status of the population and on specific target conditions. This article
      describes features of the surveys and provides examples of research on
      musculoskeletal disorders that used the survey data.

PMID- 15488699
TI  - Health services research in rheumatology: a great deal accomplished, a great deal
      left to do.
AB  - Although rheumatology has been on the cutting edge of health services research
      for decades, there are many unresolved issues for patients, clinicians, insurers,
      and policy makers. This article explore three areas in which methodologic
      controversies present tradeoffs to a health care system that is grappling with
      larger issues around cost and access to care. Specifically, we examine issues
      around the use of large databases, the appropriate instruments for measuring
      patient-centered outcomes, and the questions that are raised from cost
      effectiveness studies of new treatments for rheumatoid arthritis. The issues are
      presented in the context of a need to provide better information to those who are
      providing care and those who are paying for it.

PMID- 15488700
TI  - Animal models for atopic dermatitis: are they relevant to human disease?
AB  - Over the last decade, animal models of atopic dermatitis (AD) have received
      increasing attention. They include NC/Nga mice, a hapten-induced mouse model, and
      transgenic and knockout mouse models. Although the pathogenesis of skin
      inflammation elicited in these models and that in AD are not quite the same, it
      is pertinent to ask what these animal models really tell us about the
      pathogenesis and possible therapies for the disease. NC/Nga mice may yield
      information relevant to the dissection of the crucial components of the
      pathophysiology of AD rather than the assessment of potentially therapeutic
      agents for its treatment. A hapten-induced mouse model created by repeated
      application of 2,4,6-trinitrochlorobenzene (TNCB) is a simple and reproducible
      one. This model offers several advantages over others: by changing hapten and the
      mouse strain used, various types of chronic inflammation, probably reflecting
      heterogeneity in clinical presentation of AD, can be induced; this model is also
      of enormous value in its high reproducibility as well as the ease of quantitative
      assessment by measuring ear thickness. Among various transgenic and knockout
      mouse models, the IL-18-transgenic mouse is one of the closest available mouse
      models of human AD, although the onset of the AD-like lesions in the IL-18
      transgenic mice is such a late event. Although these mice all have significant
      disadvantages, it is important to review the current literature on the models in
      the hope that one may identify useful areas for investigation.

PMID- 15488701
TI  - Leukemia inhibitory factor-transfected embryonic fibroblasts and vascular
      endothelial growth factor successfully improve the skin substitute wound healing
      by increasing angiogenesis and matrix production.
AB  - BACKGROUND AND OBJECTIVE: The combined application of cytokines on embryonic
      fibroblasts and dermal substitute were studied for optimal skin defect coverage.
      The mechanism of combined treatment of leukemia inhibitory factor (LIF)
      transfected embryonic fibroblasts and vascular endothelial growth factor (VEGF)
      were elucidated and subsequently the in vivo applications of both were tested in
      an artificial dermal substitute. METHODS: Mouse embryonic fibroblast cells, BALB
      3T3, were stably transfected with mouse full-length LIF cDNA and added to various
      doses of VEGF for detection of signaling interaction. LIF-transfected cells and
      VEGF treatment were tested with pig-tendon derived collagen dermal substitute in
      the backs of BALB/c male mice up to for 14 days. RESULTS: LIF-transfected cells
      as well as vector-transfected fibroblasts significantly proliferated by 1, 10, or
      100 ng VEGF on days 3 and 5. Erk mitogen-activated protein (MAP) kinase
      phosphorylation was observed from 1 to 30 min in LIF-transfected and 10 ng of
      VEFG, and 1 to 60 min in LIF-transfected and 100 ng VEFG treatments. The cellular
      fibronectin levels also increased in LIF-transfected cells with 10 and 100 ng
      VEGF additions. In in vivo analyses, LIF-transfected embryonic fibroblasts with
      50 microg of VEGF markedly enhanced collagen I expression and CD34 angiogenic
      marker on days 7 and 14. CONCLUSION: LIF transfection and VEGF treatment enhanced
      phosphorylated-Erk-MAP kinase in vitro. In vivo study revealed that the combined
      application of LIF transfection of embryonic fibroblasts with an angiogenic
      factor such as VEGF in the template of a dermal substitute induced greater skin
      collagen production and angiogenesis in the dermal substitute.

PMID- 15488702
TI  - Different gene expression profile observed in dermal papilla cells related to
      androgenic alopecia by DNA macroarray analysis.
AB  - BACKGROUND: Androgenic alopecia (AGA) is the most common type of baldness in men.
      Although etiological studies have proved that androgen is one of the causes of
      this symptom, the defined molecular mechanism underlying androgen-related actions
      remains largely unknown. OBJECTIVES: To clarify the difference in the gene
      expression profile of dermal papilla cells (DPCs) in skin affected by baldness.
      METHODS: DNA macroarray study was carried out on cultured DPCs from AGA skin
      comparing with DPCs from skin that is not affected by baldness. RESULTS: From DNA
      macroarray analysis, we observed that 107 of the 1185 analyzed genes had
      differing expression levels. A marked difference was observed in the decreased
      gene expression of BMP2 and ephrin A3 and up-regulated in NT-4 gene. In order to
      clarify the roles of BMP2 and ephrin A3 in the hair follicles, we examined the
      proliferation of hair follicle keratinocyte and expression of a hair acidic
      keratin gene. Both BMP2 and ephrin A3 raised the proliferation rate of the outer
      root sheath cells (ORSCs) and induced gene expression in acidic hair keratin 3
      II. CONCLUSION: These results lead us to the hypothesis that both BMP2 and ephrin
      A3 function as hair growth promoting factors in the hair cycle.

PMID- 15488703
TI  - Detection of various types of human papillomavirus DNA, mainly belonging to the
      cutaneous-group, more frequently in normal tissue than in squamous cell
      carcinomas of the lip.
AB  - BACKGROUND: Mucosal high-risk human papillomaviruses (HPVs), such as type 16, are
      detectable in oral cancers, especially of the oropharynx and tonsils, and there
      is evidence that they play a pathogenetic role in some cases. However,
      information is limited about their significance for cancers of the vermilion of
      the lip. OBJECTIVE: To determine the detection rate, types and localization of
      HPVs in squamous cell carcinomas (SCCs) of the lip. METHODS: Nested PCR for
      cutaneous HPVs, including epidermodysplasia verruciformis-related HPV (EV-HPV),
      and single PCR for mucosal HPVs, were conducted for a total of 27 SCCs and normal
      samples from 30 individuals. Tyramide-based in situ hybridization (ISH) was also
      applied. RESULTS: Various types of HPVs were detected, particularly from normal
      individuals. Among the kinds of the HPV types detected in this study, half were
      found by PCR using a primer pair, which we newly designed. The prevalence of HPV
      was 5 out of 27 SCCs (ca. 18%) and 10 out of 30 normal individuals (ca. 33%).
      They were the entire cutaneous-group except for two, from one SCC and one normal
      individual. CONCLUSION: On the surface of the normal lip various types of mainly
      cutaneous-group HPVs may be present, but there does not appear to be any obvious
      association with SCCs developing in this site.

PMID- 15488704
TI  - TGF-beta is not involved in early phase growth inhibition of keratinocytes by
      1alpha,25(OH)2vitamin D3.
AB  - BACKGROUND: It has been proposed that transforming growth factor-beta (TGF-beta)
      is involved in the growth inhibition of normal human epidermal keratinocytes
      (NHEK) by 1alpha,25-dihydoxyvitamin D(3) (1alpha,25(OH)(2)D(3)), although this is
      still controversial because of the difficulty in blocking TGF-beta activity
      completely. OBJECTIVE: To determine whether TGF-beta is involved in early phase
      growth inhibition by 1alpha,25(OH)(2)D(3). METHODS: TGF-beta mRNA was detected by
      ribonuclease protection assay (RPA), and biological active TGF-beta was
      determined by a luciferase reporter assay. To block intrinsic TGF-beta activity
      completely, we constructed an adenovirus vector expressing a truncated TGF-beta
      type II receptor with a dominant negative effect (AdexTbetaTR) that blocks TGF
      beta signal transduction. RESULTS: 1alpha,25(OH)(2)D(3) slightly upregulated TGF
      beta1 and TGF-beta2 after 24 h according to an RPA and a luciferase reporter
      assay, however growth inhibition by 1alpha,25(OH)(2)D(3) occurred at 6 h. The
      addition of 10(-6) M of 1alpha,25(OH)(2)D(3) to NHEK infected with AdexTbetaTR or
      AdexLacZ (control vector) reduced DNA synthesis to 59.3 and 62.2% at 6 h,
      respectively. There was no significant difference in cell number after a 3-day
      incubation with AdexTbetaTR or AdexLacZ-infected cells treated with
      1alpha,25(OH)(2)D(3). CONCLUSION: Since 1alpha,25(OH)(2)D(3) rapidly inhibits
      NHEK growth regardless of the prevention of TGF-beta signal transduction, TGF
      beta is not involved in early phase growth inhibition by 1alpha,25(OH)(2)D(3).

PMID- 15488705
TI  - Hapten-induced contact hypersensitivity is enhanced in Tyk2-deficient mice.
AB  - BACKGROUND: Previous studies have shown that Tyk2, a member of the Janus family
      of protein tyrosine kinases, which are activated by a variety of cytokines, plays
      a crucial role in interleukin (IL)-12-mediated T-cell functions such as IFN-gamma
      production. On the other hand, hapten-induced contact hypersensitivity (CHS) is
      mediated by IFN-gamma producing CD8+ T cells and regulated by CD4+ T cells.
      OBJECTIVE: This study hypothesized that the CHS response might be reduced in Tyk2
      deficient mice because of a lack of IFN-gamma production from CD4+ and CD8+ T
      cells. METHODS: The CHS reaction was evoked in wild-type and Tyk2-deficient mice
      and the ears of the mice were examined to measure for several cytokines. RESULTS:
      Ear swelling during CHS was significantly enhanced in Tyk2-deficient mice
      compared with the controls. IL-12 and IFN-gamma levels at the reaction sites in
      Tyk2-deficient mice were significantly lower than in the controls, whereas IL-2
      and IL-4 levels were elevated. Furthermore, STAT3- and STAT4-phosphorylation in
      the draining lymph node cells of Tyk2-deficient mice decreased. CONCLUSION: These
      results suggest that the lack of Tyk2-mediated signal transduction enhances a
      compensative pathway during CHS.

PMID- 15488706
TI  - Serological detection of eotaxin, IL-4, IL-13, IFN-gamma, MIP-1alpha, TARC and IP
      10 in chronic autoimmune urticaria and chronic idiopathic urticaria.

PMID- 15488707
TI  - Epidermal growth factor activates m-calpain, resulting in apoptosis of HaCaT
      keratinocytes.

PMID- 15488708
TI  - In vivo evidence for close association of CLA expression and E-selectin binding
      by T cells in the inflamed skin.

PMID- 15488709
TI  - Synergistic anti-tumor effect by combinatorial gene-gun therapy using IL-23 and
      IL-18 cDNA.

PMID- 15488710
TI  - A rod-linker-contained R-phycoerythrin complex from the intact phycobilisome of
      the marine red alga Polysiphonia urceolata.
AB  - A linker-contained R-phycoerythrin (R-PE) complex was obtained by the Sephadex G
      150 column chromatography from the Polysiphonia urceolata phycobilisome (PBS)
      that was dis-associated at 37 degrees C for 6 h in the dilute phosphate buffer
      (pH 7.0) with 5% (m/v) sodium dodecyl sulfate (SDS). The R-PE complex showed
      three absorption peaks at 498, 538 and 567 nm, and a fluorescence emission
      maximum at 578 nm. Polypeptide analysis of the complex by the 8-25% (m/v)
      gradient SDS-polyacrylamide gel electrophoresis demonstrated that it contained
      three red subunits, alpha(PE)(17.6),beta(PE)(19.2) and gamma(PE)(31.0), and a
      colorless 35.3 kDa rod-linker L(R)(35.3). Polypeptide proportion of the complex
      demonstrated that it was a hexamer in aggregate form gamma(PE)(31.6),
      (alpha(PE)(17.6),beta(PE)(19.2))(3)L(R)(35.3)(alpha(PE)(17.6),beta(PE)(19.2)(3)ga
      ma(PE)(31.6) which is proposed to originate from a rod assembly of hexamer-linker
      hexamer the substructure alpha(PE)(17.6),beta(PE)(19.2)(3) of which was
      decomposed off from the ends of the assembly during the PBS dissociation. The
      distinctive stability of the prepared hexamer is attributed to a large extent to
      the electrostatic interaction among its polypeptides, but not to the hydrophobic
      interaction.

PMID- 15488711
TI  - Light effect and reactive oxygen species in the action of ciprofloxacin on
      Staphylococcus aureus.
AB  - Oxygen consumption by Staphylococcus aureus ATCC 29213 sensitive to ciprofloxacin
      was determined with an oxygen selective electrode. Increase in the O(2)
      consumption was observed with 0.45 micromL(-1) ciprofloxacin while higher
      concentrations gave rise to a reduction of O(2) consumption. Resistant S. aureus
      strain did not show increase of O(2) consumption in presence of ciprofloxacin.
      Nitro Blue Tetrazolium assay showed that production of reactive oxygen species
      (ROS) increased intracellularly in sensitive bacteria incubated with this
      antibiotic. The exposition to UV light (360 nm) augmented the intracellular
      oxidative stress of S. aureus and provoked increment of ROS in extracellular
      media. Generation of singlet oxygen O(2) ((1)Delta(g)) in S. aureus was measured
      by means of oxidation of methionine. The absorbance of methionine was monitored
      at 215 nm and a clear decrease was detected when sensitive S. aureus was stressed
      with ciprofloxacin. Sodium azide and 2,5-dimethylfuran were used to reinforce the
      evidence of O(2) ((1)Delta(g)) generation during oxidative stress. Assays with
      methionine and 2,5-dimethylfuran demonstrated that resistant S. aureus did not
      increase the production of O(2) ((1)Delta(g)) in the presence of antibiotic. DNA
      oxidation was investigated in presence of O(2) ((1)Delta(g)) generated by laser
      excitation of perinaphthenone and subsequent energy transfer. Deactivation of
      O(2) ((1)Delta(g)) by reaction with DNA of sensitive and resistant bacteria was
      observed. According to the results obtained, the effect of ciprofloxacin in S.
      aureus led to an increment of O(2) ((1)Delta(g)) generating oxidative stress in
      the bacteria.

PMID- 15488712
TI  - An experimental and theoretical model for solar UVA-irradiation of soluble
      eumelanin: towards modelling UVA-photoreactions in the melanosome?
AB  - A model is developed for the UVA-irradiation of soluble eumelanin exposed to
      levels of irradiation comparable to sunlight. Radical production was determined
      in soluble dl- and l-dopa melanins exposed to solar levels of UVA, using electron
      spin resonance spectroscopy and the spin trap 5,5-dimethyl-1-pyrroline N-oxide
      (DMPO). Steady-state concentrations of DMPO-O(2)H(.-), which increased up to 0.3
      mg/ml melanin, and then declined above 0.3 mg/ml, were detected at pH 4.5. The
      kinetic model incorporated the photosensitizing and radical-scavenging reactions
      of eumelanin, and assumed semiquinone radical reduction of oxygen to be fast
      compared to disproportionation. The model is consistent with experimental data
      for melanin concentrations <0.1 mg/ml; but >0.1 mg/ml melanin is consistent only
      with data at raised oxygen tension. The rate-constant for reaction of the melanin
      semiquinone-radical and oxygen is estimated to be 10(3) mol(-1)dm(3)s(-1). In
      this model, where DMPO competes with melanin for HO(2)(.-), at ambient oxygen
      levels, eumelanin exposed to solar levels of UVA photosensitizes superoxide at
      concentrations <0.3 mg/ml melanin, and is increasingly stable towards oxidation
      when >0.3 mg/ml concentration. Eumelanin could have a negligible screening effect
      <0.1 mg/ml and very strong screening >1 mg/ml. This model would be biologically
      relevant if soluble forms of eumelanin were shown to exist in vivo, and is
      potentially useful for studies of the photochemistry and photophysics of
      eumelanin and phaeomelanin and to explore the effects of metal-ions, proteins and
      lipids in a model system.

PMID- 15488713
TI  - Molecular organization of the antifungal and anticancer drug 2-(2,4
      dihydroxyphenylo)-5,6-dichlorobenzothiazole (dHBBT) in solution and in lipid
      membranes studied by means of electronic absorption spectroscopy.
AB  - 2-(2,4-Dihydroxyphenylo)-5,6-dichlorobenzthiazole (dHBBT) is a new drug from the
      group of chemical compounds characterized by documented antifungal,
      antibacterial, cytostatic as well as antitumour activity. Despite general
      knowledge regarding pharmacological importance of dHBBT its interaction to
      biomembranes has not been investigated. In this work, we present the electronic
      absorption spectroscopic study on molecular organization of dHBBT in organic
      solvents and on its localization and molecular organization within model lipid
      membranes formed with dipalmitoylphosphatidylcholine (DPPC). The spectroscopic
      measurements are interpreted within the framework of the exciton splitting
      theory. It is concluded that complex absorption spectrum of dHBBT both in the
      organic solvents and incorporated to DPPC represents superposition of two
      spectral forms: representing monomers and hypsochromically shifted spectrum
      representing molecular dimers. Analysis of the temperature dependencies of the
      absorption spectra of dHBBT incorporated to DPPC liposomes suggests localization
      of the drug in the polar head-group region of the membrane or in the region of
      the polar-nonpolar interface. Linear dichroism measurements of dHBBT incorporated
      to DPPC multibilayers reveal roughly vertical orientation of the drug molecules
      with respect to the plane of the membrane. A model is presented of molecular
      organization of dHBBT in lipid membranes. Potential effects of dHBBT on membrane
      physical properties is briefly discussed.

PMID- 15488714
TI  - Annual variation of the angular distribution of the UV beneath public shade
      structures.
AB  - Local governments provide many shade structures at parks and sporting ovals for
      public use. However, the question remains of how effective are public shade
      structures at reducing biologically effective UV radiation throughout the year?
      Broadband measurements of the angular distribution of scattered UV beneath three
      specific public shade structures was conducted for relatively clear skies and for
      a solar zenith angle (SZA) ranging from 13 degrees to 76 degrees. The ultraviolet
      protection factors (UPF) for the shade structures ranged from 18.3 to 1.5 for an
      increasing SZA. Measurements showed that the horizontal plane received the
      highest SUV levels from the SZA of 28 degrees to 75 degrees, 42 degrees to 76
      degrees, and 50 degrees to 76 degrees for the small, medium and large structures,
      respectively. This was due to the angle of the sun causing the shade created by
      the shade structure to be outside the structure. For the small shade structure,
      the measurements directed to the west were the highest levels in the shade after
      approximately 28 degrees. For the medium and large shade structures, the
      measurements directed to the west and south were the highest levels in the shade
      after roughly 42 degrees and 50 degrees, respectively.

PMID- 15488715
TI  - Psoralen derivatives and longwave ultraviolet irradiation are active in vitro
      against human melanoma cell line.
AB  - Cutaneous malignant melanoma is a very serious form of skin cancer that arises
      from melanocytes. Currently there is no effective treatment for metastatic
      melanoma so intense clinical trials are evaluating new drugs for this human
      malignancy. Psoralens are a group of compounds that bind to DNA in rapidly
      dividing cells and with ultraviolet light in the A band (UVA) cause DNA
      crosslinking, thereby preventing cellular division. They are used in the
      treatment of psoriasis and cutaneous T-cell lymphoma among other skin and blood
      diseases. We have investigated the cytotoxic potential of three psoralen
      derivatives plus UVA exposure (PUVA) on a established cell line of human
      melanoma. Cells were treated with different concentrations of 8-methoxypsoralen
      (8-MOP), 4,5',8-trimethylpsoralen (TMP) and 7-methylpyridopsoralen (MPP), for 1 h
      and after exposure to UVA light (0.3 J/cm(2)) were allowed to recover over a 24
      72 h period. Viability was assessed by the microculture 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Cisplatin, one of
      the most important drugs in the chemotherapy of melanoma, was included for
      comparative studies. All the psoralen derivatives tested were markedly cytotoxic
      in a dose and post-exposure-time dependent manner. The IC(50) values for 72 h of
      post-exposure time were as follows: MPP=0.05+/-0.01, TMP=0.13+/-0.003 and 8
      MOP=10.79+/-1.85 micromol/L. Regardless of the limitations of the in vitro model,
      our results suggested that the lower IC(50) values of TMP and MPP might be of
      clinical importance.

PMID- 15488716
TI  - TD-DFT calculations of the potential energy curves for the trans-cis photo
      isomerization of protonated Schiff base of retinal.
AB  - One-dimensional potential energy curves for the isomerization of protonated
      Schiff base of retinal (PSBR) in bacteriorhodopsin (bR), i.e., isomerization from
      all-trans- to 13-cis-forms, have been calculated by means of time-dependent
      density functional theory (TD-DFT) calculations, in order to elucidate the
      mechanism of initial step in photo-absorption. The transition state of the
      isomerization in the first excited state is located at theta(13-14)=58 degrees ,
      where theta(13-14) means twist angle around the C(13)=C(14) double bond of PSBR
      The potential barrier is formed by the avoided crossing between S(1) (B(u)-like)
      and S(2) (A(g)-like) states. The mechanism of the isomerization was discussed on
      the basis of theoretical results.

PMID- 15488717
TI  - Effects of UV-B radiation on the Patagonian Jaborosa magellanica Brisben.
AB  - Treatment of Jaborosa magellanica with artificial UV-B radiation caused changes
      in plant growth, plant chemistry and increase DNA polymorphisms.
      Spectrophotometric analysis showed that UV-B radiation decreases the chlorophylls
      content, and increases the amount of UV-B absorbing compounds (e.g.,
      phenylpropanoids). Other UV-induced alterations include reduction in leaf area,
      alterations in plant architecture, and DNA damage. Using random primers and PCR
      amplification procedure, a high degree of polymorphism was detected when treated
      plants were compared to non-irradiated plants. These biochemical changes may be
      interpreted as plant response to UV-B radiation stress and as an indicator of DNA
      damage.

PMID- 15488718
TI  - Mononuclear and binuclear ruthenium(II) heteroleptic complexes based on 1,10
      phenanthroline ligands. Part II: Spectroscopic and photophysical study in the
      presence of DNA.
AB  - Photophysical and photochemical properties of a series of mononuclear and
      binuclear ruthenium(II) complexes of phen (phen=1,10-phenanthroline), in the
      absence or in the presence of calf-thymus DNA have been investigated by steady
      state as well as time-resolved methods. The complexes of this series are
      [Ru(x)(phen)(2x)(L)](2x+) (x=1 or 2) type, where L is a bpy (4,4'-dimethyl-2,2'
      bypiridine, with x=1) or a bis-bpy covalently linked by flexible chains including
      either polymethylene groups or polyamine functions (with x=2). Upon addition of
      DNA, the most important increasing luminescence and change of emission maxima
      wavelength are observed for the bimetallic compounds having amine functions in
      their spacer. A biexponential decay in luminescence is found with emission
      lifetimes of the complexes upon binding to DNA. Moreover, these complexes induce
      efficient photocleavage of DNA by irradiation at 450 nm. This efficiency is
      particularly important when the binuclear complexes include amino groups.
      Topoisomerization experiments have pointed out a similarity between the DNA
      cleaving ability of these complexes and their intercalation into DNA. Scavenging
      experiments have shown that the oxidative species involved in DNA cleavage was
      mainly (1)O(2), via a type II mechanism.

PMID- 15488719
TI  - Interference of ruthenium red analogues at photosystem II of spinach thylakoids.
AB  - The effect of ruthenium red analogues on several thylakoid photosynthetic
      activities has been investigated. RR, RV, RRPh1, RRPh2 and Ph inhibit ATP
      synthesis and electron flow from water to MV (basal, phosphorylating and
      uncoupled) as their concentration increases, thus, they act as a Hill reaction
      inhibitor. They inhibit uncoupled electron transport through PSII from water to
      DCPIP and partially from DPC to DCPIP. However, these compounds do not affect
      uncoupled PSI electron transport from DCPIP to MV. Therefore, the target of
      interaction is at the level of OEC and the span P(680) to Q(A) for RR, RRPh1 and
      RRPh2. Chlorophyll a fluorescence studies corroborate the already found
      interference sites and may affect the disconnection between chlorophyll molecules
      within the LHCII and/or between antennae and RCs, or decreases the exciton to
      reach the RC and inhibition of PSII occurs. RRPh2 is six times more active than
      RR. Finally, Ph inhibits electron flow interacting at the level of Q(B).

PMID- 15488720
TI  - Effect of binary and ternary polyvinylpyrrolidone and/or hydroxypropyl-beta
      cyclodextrin complexes on the photochemical and photosensitizing properties of
      Naproxen.
AB  - The effect of the polyvinylpyrrolidone and/or hydroxypropyl-beta-cyclodextrin on
      the photo-lability of aqueous solutions of the anti-inflammatory drug Naproxen
      was studied. Kinetic studies revealed that the presence of all of these additives
      reduced drug photodegradation. In all cases, the presence of the different
      additives elicited a change in the photomixture composition, being the alcoholic
      derivative the major photoproduct formed. Nevertheless, the change in the
      efficiency of the process and the amount of the photoproducts formed in the
      different systems were not related with the biodamage produced by the drug. In
      this sense, the presence of free Naproxen clearly sensitized the
      photoperoxidation of linoleic acid. The photosensitizing effect decreased as the
      PVP concentration increased. Different protection provides the binary
      (Naproxen:HP-beta-CD) and ternary (Naproxen:HP-beta-CD:PVP) complexes. The binary
      complex formation had not effect on the prevention of photooxidation of linoleic
      acid sensitized by the drug, whereas the ternary complex formation suppresses the
      drug effect. The different behaviour observed with beta-CD and HP-beta-CD and the
      structural differences of both cyclodextrins seem to indicate that in the case of
      the HP-beta-CD the linoleic binds with the CD and takes contact with the drug.
      These results confirm that in these systems the prevention of biodamage would be
      due to a decrease in the contact between the short-lived species generated during
      Naproxen photodegradation and biological structures, rather than due to the
      nature or amount of the photoproducts. In addition, the ability of the complex to
      interact with the biological structure depends on the structure of both
      interacting species.

PMID- 15488721
TI  - Sensitised decomposition of microcystin-LR using UV radiation.
AB  - UV radiation was applied to degrade cyanobacterial hepatotoxin, microcystin-LR in
      the presence of phycocyanin as a model natural sensitiser. The concentrations of
      both the toxin and the pigment used in the experiments were higher by several
      orders of magnitude than found in the environment. The photoreaction parameters
      were optimised. The process was found to be of limited use for water treatment
      due to its low efficacy. Additionally, pronounced UV-induced bleaching of the
      pigment significantly reducing the photoreaction rates of the toxin was observed
      for the highest UV radiation intensities applied.

PMID- 15488722
TI  - Transfusion induced immunomodulation: myth or reality?

PMID- 15488723
TI  - [Perspectives and organisation of haemovigilance in compliance with the European
      Directive 2002/98/EC].
AB  - Haemovigilance has been a new concept in transfusion medicine since 1994. After
      10 years, the situation can be assessed to evaluate the efficiency of the
      national organisation in each European country. Now, the new European Directive
      states the main orientations in the field of haemovigilance. Now, this inventory
      of the haemovigilance network shows a very heterogeneous and diverse situation.
      The frequency of transfusion reactions/incidents in recipients is more than 325
      per 10(5) blood components in France, whereas in the United Kingdom it is 8.5 for
      10(5) blood products! The systems and the organisation are different but the
      essential aim is to increase public health safety. In this article, we propose
      seven principles to organise the future of European haemovigilance.

PMID- 15488724
TI  - [The precautionary principle applied to blood transfusion. What is its impact on
      practices and risk management?].
AB  - The precautionary principle has boomed in the French public health sector through
      blood transfusion. There has been, however, no perambulatory reflection on the
      definition, objectives, methods of application or consequences of this principle.
      The question of the pertinence of its application remains unanswered. This study,
      based on interviews with blood transfusion practitioners, aims to establish their
      perceptions of the precautionary principle's application in this specific field
      and of its consequences in terms of risk management and patients' rights. The
      pros and cons of this application are analysed based on these perceptions.
      According to our analysis, the precautionary principle seems to be born of
      confusion. It is seen more as a way to protect decision makers than patients and,
      if taken to extremes, could prejudice medical logic. Nevertheless, it also brings
      measures which renew and encourage evolution in transfusion risk management.

PMID- 15488725
TI  - [Factors of risk perception and risk acceptability: a contribution for the
      knowledge of the perception of the risk associated with blood transfusion].
AB  - The concept of risk cannot be limited to simply knowing the probability of
      occurrence and the seriousness of the damages caused. It's a matter of social
      construction and numerous elements contribute towards its perception and
      acceptability. These elements have been studied for 20 years or so. Some of these
      elements influence risk perception such as awfulness, unfamiliarity, the number
      of people exposed to it, other elements influence its acceptance such as
      individual perceptions, social factors, ethics and equity. Their knowledge allows
      a better understanding of the evolution of perception and of the risk
      acceptability in general and transfusion risk in particular.

PMID- 15488726
TI  - [A quality program in haemovigilance: evaluation of the blood transfusion chain].
AB  - Blood transfusion, like any effective therapy, involves an element of risk. In
      order to reduce such risks to a maximum, a legislative and statutory framework
      has been set up. A reliable evaluation of this system is necessary together with
      an efficient evaluation method whose aim is to guarantee quality service.
      Favouring the development of the evaluation of professional practices is one of
      the priorities of the National Agency of Accreditation and Evaluation in Health
      (ANAES) created in April 1996. Following the recommendations from ANAES, the
      University Hospital of Brest decided to set up an evaluation of blood transfusion
      chain from the prescription of blood products to the transfusion act and follow
      up of receivers in two health care services. The method used for this evaluation
      was a clinical audit. It is a method of evaluation, which allows with the help of
      certain criteria, care practices to be compared to accepted references, in order
      to measure the quality of these practices and the results of hospital care, so
      that improvements may be added. We present here the method and results of this
      evaluation, as well as the improvements we have put in place.

PMID- 15488727
TI  - [Ethics, motivations of plasmapheresis donors].
AB  - For 50 years, the French Blood Transfusion Service has been developing ethical
      concepts of anonymous, voluntary and non-profit donation. The subject of this
      work is the study of ethical aspects and motivations of plasmapheresis donors.
      Three hundred donors were questioned on these subjects. The questionnaire was
      created after analysing the semi-orientated interviews of ten donors. The donors
      are male, aged over 35, with relatively high social and professional backgrounds.
      The main reason given for the first donation is the request by a relative or
      another person. With regards to further donations, solidarity with patients is
      mentioned as a reason. Even if the majority of the donors are aware of the
      ethical aspects of donation, over 50% of them accept to give plasmapheresis
      regardless of these principles. Plasmapheresis donors are primarily motivated by
      solidarity reasons. Thereby, they are fully active in the evolution of society.

PMID- 15488728
TI  - [Evaluation of pre- and post-transfusion serological screening in France in
      2001].
AB  - Screening of labile blood products recipients for HIV and HCV has been performed
      in France since a government recommendation was issued in 1996. It has been
      designed to get transfusion related contamination of recipients through pre- and
      post-transfusion serological tests. Since then, residual risk has decreased
      dramatically and it was suspected that recommendations might sometimes be
      ignored. A nationwide survey has been done to measure the real screening rate and
      its cost efficacy ratio. In addition accuracy of tracability and recipients
      mortality has also been evaluated. A random sample of 1115 labile blood products
      among all the 1203 378 distributed during first semester of 2001 in France has
      been drawn. They have been matched with test results obtained in hospital files.
      Tracability has been considered accurate if name, surname and birth date of
      recipients were exactly the same both in hospital file and in the file of the
      Etablissement Francais du Sang. A total of 1092 hospital files has been
      retrieved. Pre transfusion HIV and HCV tests have been performed in 58.5 % of
      cases, 95 % CI [55.6-61.5], and post-transfusion tests in 30.5 % [28.5-35.5] of
      cases. Only 19.5% [16.6-22.6] of recipients, not known to be dead 6 months after
      transfusion, have had both pre and post-transfusion tests. No HIV or HCV
      contamination has been notified by the Haemovigilance network during the same
      period. Accuracy rate of tracability was 96.25% [94.9-97.3]. Furthermore 35.8%
      [33-38.7] of recipients were found dead within 6 months after transfusion. A
      logistic regression analysis showed that the hospital area, the hospital size
      (more than 300 beds) and the annual amount of blood bags transfused in it (less
      than 5000) were factors independently associated with having a full pre and post
      transfusion screening. Currently, the screening program may detect 0.14 cases of
      HIV and 0.05 HCV transfusion related contamination of recipient every year. The
      total cost of this program is about 20 million euro and the cost per case exceeds
      110 million euro. The program will be of no use in case of an emerging
      transmitable disease. This program does not comply to any evaluation criteria of
      screening programs and its cost efficacy ratio is very poor.

PMID- 15488729
TI  - [Satisfaction survey in general hospital personnel involved in blood transfusion:
      implementation of the ISO 9001: 2000 standard].
AB  - As part of its policy of constant quality improvement, Etablissement Francais du
      Sang (EFS) des Pays de la Loire (Pays de la Loire Regional blood transfusion
      institution) carried out a satisfaction survey among the hospital personnel
      involved in prescribing and using immuno-hematological tests and labile blood
      products. The polling tool selected by agreement between the hospital management
      and quality assurance department was a questionnaire that permitted item rating
      and free commentary. It addressed the personnel's perception of the quality of
      erythrocyte immuno-hematological (EIH) testing and of the products administered,
      as well as their perception of the quality of communications with the local EFS.
      The questionnaire was sent to 26 physicians and 32 senior nurses in 15 hospital
      departments. The reply rate was 60% and expressed a 85% overall satisfaction
      level. Dissatisfaction causes were more specifically analysed, the main one
      involving labile blood product distribution in emergency situations. A joint
      undertaking by the EFS and the hospital led to the implementation of corrective
      measures, including the writing and implementation of a common standard operating
      procedure for emergency transfusion management. The results obtained demonstrated
      the feasibility of this type of survey and the interest, to a blood transfusion
      centre and the hospital personnel involved in transfusion, of assessing their
      very own perception of service quality.

PMID- 15488730
TI  - [Andragogy: reality or utopy].
AB  - The education of adult differs from that of children and the methods, which have
      to be used, should take into account that adults have specific goals and diverse
      knowledge. As the teaching methods for children are called pedagogy, it is now
      known as andragogy for adults. Andragogy has lead to the development of several
      approaches to improve continuous education. Several tools and methodologies have
      been created for adult education.

PMID- 15488731
TI  - Discrimination between the anti-monomeric and the anti-multimeric Lewis X
      response in murine schistosomiasis.
AB  - Individuals suffering from schistosomiasis raise an immune response against
      Galbeta1-4(Fucalpha1-3)GlcNAcbeta (Lewis X, LeX), a trisaccharide that is
      expressed both in monomeric and polymeric form in different life stages of the
      schistosomes. In order to study a possible immunological discrimination between
      different presentations of LeX, i.e. as a monomer or as an oligomer (di- or
      trimer), the levels of antibodies against lacto-N-fucopentaose III (LNFPIII, a
      pentasaccharide containing monomeric LeX), and against dimeric and trimeric LeX
      have been measured in sera of mice with a schistosome infection. The antibody
      response was predominantly of the IgM type. A striking difference in intensity of
      the antibody response against monomeric and oligomeric LeX was observed.
      Furthermore, the antibody response against circulating cathodic antigen (CCA), a
      schistosomal antigen containing multimeric LeX, was also measured, and the
      response pattern differed from that of the anti-mono, di- and trimeric LeX
      responses. In addition, the binding pattern of a panel of monoclonal antibodies
      (Mabs), derived from mice infected with schistosomes, with LNFPIII, di- and
      trimeric LeX was measured by surface plasmon resonance (SPR). These Mabs could be
      divided into three different groups according to their interaction with the LeX
      oligosaccharides. Based on these data, we suggest that the different
      presentations of LeX give rise to different groups of anti-LeX antibodies.

PMID- 15488732
TI  - CD28 is required for T cell activation and IFN-gamma production by CD4+ and CD8+
      T cells in response to Trypanosoma cruzi infection.
AB  - In the present study we evaluated the mechanisms behind the implication of the
      costimulatory molecule CD28 for the immune response against the intracellular
      protozoan parasite Trypanosma cruzi. Our results reveal a critical role for CD28
      in the activation of both CD4+ and CD8+ T cells and induction of the effector
      mechanisms that ultimately mediate the control of parasite growth and
      pathogenesis in infected mice. CD28-deficient (CD28-/-) mice are highly
      susceptible to T. cruzi infection, presenting higher parasitemia and tissue
      parasitism, but less inflammatory cell infiltrate in the heart than C57Bl/6 wild
      type (WT) mice. All the infected WT mice survived acute infection, whereas 100%
      of CD28-/- mice succumbed to it. The increased susceptibility of the CD28-/- mice
      was associated with a dramatic decrease in the production of IFN-gamma by both
      CD4+ and CD8+ T cells resulting in a diminished capacity to produce nitric oxide
      (NO) and mediate parasite killing. T cell activation was also profoundly impaired
      in CD28-/- mice, which presented decreased lymphoproliferative response after the
      infection compared to WT mice. Together, these data represent the first evidence
      that CD28 is critical for efficient CD4+ T cell activation in response to T.
      cruzi infection in mice.

PMID- 15488733
TI  - Cell death, BAX activation, and HMGB1 release during infection with Chlamydia.
AB  - Infection by a number of Chlamydia species leads to resistance of the host cell
      to apoptosis, followed by induction of host-cell death. In a population of
      infected cells that displays protection against staurosporine-induced apoptosis
      among the adherent cells, we find that cells that had been recovered from the
      supernatant share characteristics of both apoptosis and necrosis, as assayed by
      the propidium iodide (PI)-annexin V double-labeling technique. Cell death was
      observed in both an epithelial cell line and primary fibroblasts, although the
      primary cells had a higher propensity to die through apoptosis than the
      immortalized cell line. Staurosporine-mediated activation of the pro-apoptotic
      BCL-2 family member, BAX, was inhibited in the epithelial cell line infected for
      32 h with the lymphogranuloma venereum (LGV/L2) but not the murine pneumonitis
      (MoPn) strain of C. trachomatis, but inhibition of staurosporine-mediated BAX
      activation disappeared after 48 h of infection with the LGV/L2 strain.
      Conversely, infection with MoPn (C. muridarum) but not LGV/L2 led to BAX
      activation after 72 h, as previously reported for shorter (48 h) infection with
      the guinea pig inclusion conjunctivitis (GPIC) serovar of C. psittaci (C.
      caviae). These results suggest that the ability to inhibit staurosporine-mediated
      BAX activation or to activate BAX due to the infection itself may vary as a
      function of the chlamydial strain. Interestingly, both the epithelial cells and
      the fibroblasts also released high mobility group box 1 protein (HMGB1) during
      infection, although much less HMGB1 was released from fibroblasts, consistent
      with the higher level of apoptosis observed in the primary cells. HMGB1 is
      released preferentially by necrotic or permeabilized viable cells, but not
      apoptotic cells. In the extracellular space, HMGB1 promotes inflammation through
      interaction with specific cell-surface receptors. Higher levels of HMGB1 were
      also measured in the genital-tract secretions of mice infected vaginally with C.
      trachomatis, compared to uninfected controls. These results suggest that cells
      infected with Chlamydia release intracellular factors that may contribute to the
      inflammatory response observed in vivo.

PMID- 15488734
TI  - The fibronectin-binding capacity and host cell adherence of Streptococcus
      pyogenes strains are discordant with each other.
AB  - Surface exposed fibronectin-binding proteins (FBPs) play an important role in the
      adherence of Streptococcus pyogenes (group A streptococcus, GAS) to host cells.
      This pathogen expresses numerous FBPs, of which SfbI, SfbII and PrtF2 are major
      surface exposed FBPs. However, GAS strains differ in the genetic potential to
      express these proteins. To test whether this difference reflects in differences
      in fibronectin (Fn) binding, a set of circulating strains previously examined for
      adherence to host cells was used. The 68 distinct strains were isolated from
      throat, skin and blood. They were analyzed for (a) the presence of genes for
      SfbI, SfbII and PrtF2 and (b) the extent of Fn binding. The results suggest that
      strains possessing two or more of the genes for these FBPs bound Fn significantly
      more than strains possessing none or one of the genes. No correlation between the
      extent of Fn binding and the tissue site of isolation was found. Furthermore,
      together with our previous studies on adherence capacity of these GAS strains, we
      found no correlation between Fn binding ability and the avidity of the strains to
      adhere to epithelial cells. We suggest that while Fn binding is important for
      adhesion, for many GAS strains the extent of Fn binding is not the critical
      determinant of adherence.

PMID- 15488735
TI  - Oral streptococcal glyceraldehyde-3-phosphate dehydrogenase mediates interaction
      with Porphyromonas gingivalis fimbriae.
AB  - Interaction of Porphyromonas gingivalis with plaque-forming bacteria is necessary
      for its colonization in periodontal pockets. Participation of Streptococcus
      oralis glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and P. gingivalis
      fimbriae in this interaction has been reported. In this investigation, the
      contribution of various oral streptococcal GAPDHs to interaction with P.
      gingivalis fimbriae was examined. Streptococcal cell surface GAPDH activity was
      measured by incubation of a constant number of streptococci with glyceraldehyde-3
      phosphate and analysis for the conversion of NAD+ to NADH based on the absorbance
      at 340 nm. Coaggregation activity was measured by a turbidimetric assay. Cell
      surface GAPDH activity was correlated with coaggregation activity (r = 0.854, P <
      0.01) with Spearman's rank correlation coefficient. S. oralis ATCC 9811 and ATCC
      10557, Streptococcus gordonii G9B, Streptococcus sanguinis ATCC 10556, and
      Streptococcus parasanguinis ATCC 15909 exhibited high cell surface GAPDH activity
      and coaggregation activity; consequently, their cell surface GAPDHs were
      extracted with mutanolysin and purified on a Cibacron Blue Sepharose column.
      Subsequently, their DNA sequences were elucidated. Purified GAPDHs bound P.
      gingivalis recombinant fimbrillin by Western blot assay, furthermore, their DNA
      sequences displayed a high degree of homology with one another. Moreover, S.
      oralis recombinant GAPDH inhibited coaggregation between P. gingivalis and the
      aforementioned five streptococcal strains in a dose-dependent manner. These
      results suggest that GAPDHs of various plaque-forming streptococci may be
      involved in their attachment to P. gingivalis fimbriae and that they may
      contribute to P. gingivalis colonization.

PMID- 15488736
TI  - Interactions of Haemophilus ducreyi and purified cytolethal distending toxin with
      human monocyte-derived dendritic cells, macrophages and CD4+ T cells.
AB  - To evaluate the early stages of the host response to chancroid bacterium
      Haemophilus ducreyi, we investigated the in vitro responses of monocyte-derived
      dendritic cells (DCs) and macrophages (MQs) to this pathogen and Haemophilus
      influenzae. The phagocytic activities and pro-inflammatory cytokine secretion
      profiles of the antigen-presenting cells (APCs) were analyzed after exposure to
      gentamycin-killed bacteria, H. ducreyi lipooligosaccharide (LOS), and purified
      cytolethal distending toxin (HdCDT). T-cell proliferation and cytokine release
      were examined after co-culturing isolated autologous CD4+ T cells with antigen
      pulsed APCs. Both the DCs and MQs phagocytosed H. ducreyi and H. influenzae, as
      estimated by flow cytometry. All of the strains induced APC secretion of TNF
      alpha, IL-6, IL-8, and IL-12, as measured by ELISA. Other human cells,
      particularly endothelial cells and fibroblasts, also produced cytokines when
      stimulated with these bacteria. Purified LOS at concentration 1 microg/ml induced
      two to threefold lower levels of cytokines than the whole bacteria, which
      indicates that other components are involved in immune activation. HdCDT
      inhibited partially the production of the aforementioned cytokines. High levels
      of IFN-gamma, but not of IL-4 and IL-13, were secreted by T cells after
      activation by either DCs or MQs that were pre-exposed to bacteria, indicating the
      Th1 nature of the immune response. The levels of T-cell proliferation induced by
      H. ducreyi were lower than those induced by H. influenzae. HdCDT-treated APCs did
      not display cytokine responses or T-cell proliferation. These results indicate
      that HdCDT intoxication, which results in progressive apoptosis of APCs, may
      hamper early stage immune responses.

PMID- 15488737
TI  - IL-10 production induced by HIV-1 Tat stimulation of human monocytes is dependent
      on the activation of PKC beta(II) and delta isozymes.
AB  - The effect of HIV-1 Tat protein on the production of IL-10, an immunosuppressive
      cytokine, was examined in human primary monocytes obtained from healthy HIV-1
      negative blood donors. As expected and in agreement with our previous data, a
      dose-dependent induction of IL-10 was observed. In addition, we showed that this
      induction is mediated by the PKC pathway: in the presence of Ro 31-8220, an
      inhibitor of all PKC isozymes, or after 48 h of PMA treatment, Tat protein
      becomes unable to stimulate IL-10 production. Among the 11 PKC isozymes, eight
      (PKC alpha, beta(I), beta(II), delta, epsilon, eta, zeta, mu) are expressed in
      monocytes. In this study, by analyzing the translocation to the membrane after
      Tat stimulation, we showed that PKC alpha, beta(I), beta(II), delta and epsilon
      isozymes are activated by Tat. Moreover, by combining different approaches
      including selective PKC inhibitors (Go6983, Go6976, hispidin and rottlerin), we
      showed that PKC beta(II) and delta isozymes are essential for the activation of
      IL-10 production in human monocytes following stimulation by HIV-1 Tat protein.

PMID- 15488738
TI  - High prevalence of phagocytic-resistant capsular serotypes of Klebsiella
      pneumoniae in liver abscess.
AB  - To better understand the role of capsular polysaccharide (CPS) K1 or K2 in
      Klebsiella pneumoniae liver abscess as well as the development of metastasis to
      eye, neutrophil phagocytosis of 70 CPS isolates including K1 (n = 23)/K2 (n =
      10), non-K1/K2 (n = 37) was evaluated by flow cytometry, fluorescence imaging,
      and electron microscopy. K1/K2 isolates were significantly more resistant to
      phagocytosis (P < 0.0001) than non-K1/K2 isolates and displayed increased
      resistance to intracellular killing. Although mucoid phenotype (M-type) K1/K2
      isolates were significantly more resistant to phagocytosis (P = 0.0029) than M
      type non-K1/K2, no significant difference in the phagocytosis rate was observed
      between K1/K2 isolates with M-type and non-M-type (P = 0.0924). Mucoidy is an
      associated factor that was predominant in K1/K2 isolates, but which itself is not
      an independent influence on phagocytic resistance. The K1/K2 CPS proved
      significantly more resistant to phagocytosis than non-K1/K2 CPS in liver abscess
      isolates (P < 0.0001) and non-abscess isolates (P = 0.0001), suggesting that
      K1/K2 isolates were generally more virulent in both liver abscess and in non
      liver abscess conditions. These findings indicate that resistance of CPS K1 or K2
      K. pneumoniae to phagocytosis and intracellular killing presumably contributes to
      their high prevalence in liver abscess and uniquely in endophthalmitis.

PMID- 15488739
TI  - Molecular evidence of new variant Brucella in North Pacific common minke whales.
AB  - Brucella, a causative agent of brucellosis, has been isolated recently from a
      variety of marine mammals. The molecular analysis of marine mammalian Brucella
      strains, without manifest pathology of brucellosis in the eastern North Atlantic,
      showed that they are distinct from terrestrial Brucella species. Previously, we
      reported abnormal gonads in common minke whales (Balaenoptera acutorostrata) in
      the western North Pacific and suggested the presence of Brucella infection in the
      whales in pathology and serology studies. In the present study, using polymerase
      chain reaction (PCR), Brucella was detected in granular testes of the whales
      showing caseation or calcification. The insertion of an IS711 transposable
      element specific for marine mammal isolates as well as a seal isolate-specific
      DNA fragment were also found. Molecular characterization of Brucella based on
      sequence analysis of the PCR products amplified from the outer membrane protein
      (omp) 2 gene showed that the Brucella from North Pacific common minke whales was
      different from terrestrial and North Atlantic marine mammal Brucella strains. The
      North Pacific Brucella showed the highest similarity to North Atlantic seal
      strains among the known Brucella strains.

PMID- 15488740
TI  - Re-structuring the host cell: up close with Salmonella's molecular machinery.
AB  - A common theme in bacterial disease is the manipulation of the eukaryotic
      cytoskeleton by pathogenic factors. Understanding how virulence factors operate
      to achieve these alterations is a growing and important research effort. This
      review focuses on several virulence factors from the pathogen Salmonella, and
      considers the contributions of structural biology to our appreciation of
      bacterial modulation of cytoskeletal dynamics.

PMID- 15488741
TI  - Epstein-Barr virus: exploiting the immune system by interfering with defective
      ribosomal products.
AB  - The interaction of cytotoxic T lymphocytes with major histocompatibility complex
      (MHC)-peptide complexes is a critical step toward the initiation and propagation
      of specific immune responses against viral infection. Here we review new
      evidence, taking Epstein-Barr virus as an example, showing that defective
      ribosomal products provide an important supply of endogenous peptides for entry
      into the MHC class I antigen-presentation pathway.

PMID- 15488742
TI  - RAGE (receptor for advanced glycation end products): a central player in the
      inflammatory response.
AB  - The present review focuses on the role of RAGE, the "receptor for advanced
      glycation end products", in the inflammatory response. RAGE is a multiligand
      receptor that propagates cellular dysfunction in several inflammatory disorders,
      in tumors and in diabetes. RAGE is expressed at low levels in normal tissues, but
      becomes upregulated at sites where its ligands accumulate. RAGE may play a dual
      role in the inflammatory response: (i) interaction of RAGE on leukocytes or
      endothelial cells (ECs) with its ligands results in cellular activation involving
      the transcription factor NF-kappaB; (ii) on the other hand, RAGE on ECs may
      function as an adhesive receptor that directly interacts with leukocyte ss2
      integrins, thereby directly being involved in inflammatory cell recruitment.
      These different aspects are discussed in the present review.

PMID- 15488743
TI  - Comparative and evolutionary genomics of Yersinia pestis.
AB  - Yersinia pestis is the causative agent of plague, causing three human plague
      pandemics in history. Comparative and evolutionary genomics of Y. pestis are
      extensively discussed in this review. Understanding the genomic variability and
      the adaptive evolution of Y. pestis from the genomic point of view will
      contribute greatly to plague detection, identification, control and prevention.

PMID- 15488744
TI  - Why are most rhizobia beneficial to their plant hosts, rather than parasitic?
AB  - Multiple strains per plant and root-to-root (not seed-borne) transmission should
      favor rhizobia that invest in their own reproduction, rather than symbiotic N2
      fixation, as analogous factors may favor pathogen virulence. But legumes can
      select for greater mutualism, controlling nodule O2 supply and reducing
      reproduction of rhizobia that fix less N2.

PMID- 15488745
TI  - Design and implementation of the GLIF3 guideline execution engine.
AB  - We have developed the GLIF3 Guideline Execution Engine (GLEE) as a tool for
      executing guidelines encoded in the GLIF3 format. In addition to serving as an
      interface to the GLIF3 guideline representation model to support the specified
      functions, GLEE provides defined interfaces to electronic medical records (EMRs)
      and other clinical applications to facilitate its integration with the clinical
      information system at a local institution. The execution model of GLEE takes the
      "system suggests, user controls" approach. A tracing system is used to record an
      individual patient's state when a guideline is applied to that patient. GLEE can
      also support an event-driven execution model once it is linked to the clinical
      event monitor in a local environment. Evaluation has shown that GLEE can be used
      effectively for proper execution of guidelines encoded in the GLIF3 format. When
      using it to execute each guideline in the evaluation, GLEE's performance
      duplicated that of the reference systems implementing the same guideline but
      taking different approaches. The execution flexibility and generality provided by
      GLEE, and its integration with a local environment, need to be further evaluated
      in clinical settings. Integration of GLEE with a specific event-monitoring and
      order-entry environment is the next step of our work to demonstrate its use for
      clinical decision support. Potential uses of GLEE also include quality assurance,
      guideline development, and medical education.

PMID- 15488746
TI  - The aging of a clinical information system.
AB  - The senescence of a clinical information system is more likely to have
      administrative than technical bases. Supporting this claim is a case study of one
      aging oncology information system. The case study is qualitative, as behooves the
      subject matter. Content analysis of several documents suggests that the change in
      job description of the data coordinator led to a workflow breakdown. Next, twenty
      two individuals were interviewed. Notes from the interviews were coded, and the
      resulting patterns led to partial support for the workflow breakdown conjecture,
      refutation of the hypothesis that users disliked the character-based, human
      computer interface, support of the conjecture that political rather than
      technical factors drive the usage patterns of the system, and evidence that
      'political' activity will determine the future of the information system. A
      stakeholder matrix is proposed that addresses administrative concerns. Also, the
      issue of the uniqueness of any oncology clinical information system is linked to
      the plans for this legacy system.

PMID- 15488747
TI  - A framework for a distributed, hybrid, multiple-ontology clinical-guideline
      library, and automated guideline-support tools.
AB  - Clinical guidelines are a major tool in improving the quality of medical care.
      However, most guidelines are in free text, not in a formal, executable format,
      and are not easily accessible to clinicians at the point of care. We introduce a
      Web-based, modular, distributed architecture, the Digital Electronic Guideline
      Library (DeGeL), which facilitates gradual conversion of clinical guidelines from
      text to a formal representation in chosen target guideline ontology. The
      architecture supports guideline classification, semantic markup, context
      sensitive search, browsing, run-time application, and retrospective quality
      assessment. The DeGeL hybrid meta-ontology includes elements common to all
      guideline ontologies, such as semantic classification and domain knowledge; it
      also includes four content-representation formats: free text, semi-structured
      text, semi-formal representation, and a formal representation. These formats
      support increasingly sophisticated computational tasks. The DeGeL tools for
      support of guideline-based care operate, at some level, on all guideline
      ontologies. We have demonstrated the feasibility of the architecture and the
      tools for several guideline ontologies, including Asbru and GEM.

PMID- 15488748
TI  - Identifying projected clusters from gene expression profiles.
AB  - In microarray gene expression data, clusters may hide in certain subspaces. For
      example, a set of co-regulated genes may have similar expression patterns in only
      a subset of the samples in which certain regulating factors are present. Their
      expression patterns could be dissimilar when measuring in the full input space.
      Traditional clustering algorithms that make use of such similarity measurements
      may fail to identify the clusters. In recent years a number of algorithms have
      been proposed to identify this kind of projected clusters, but many of them rely
      on some critical parameters whose proper values are hard for users to determine.
      In this paper, a new algorithm that dynamically adjusts its internal thresholds
      is proposed. It has a low dependency on user parameters while allowing users to
      input some domain knowledge should they be available. Experimental results show
      that the algorithm is capable of identifying some interesting projected clusters.

PMID- 15488749
TI  - Correspondence analysis of microarray time-course data in case-control design.
AB  - Although different statistical approaches have been proposed for analyzing
      microarray time-course data, method for analyzing such data collected using the
      popular case-control design in clinical investigations has not been proposed
      perhaps due to the increased complexity for the existing parametric or non
      parametric approaches. In this paper, we introduce a new multivariate data
      analyzing technique, the correspondence analysis, to analyze the high dimensional
      microarray time-course data in case-control design. We show, through an example
      on type 2 diabetes, how the nice features of the correspondence analysis can be
      use to explore the various time-course gene expression profiles that exist in the
      data. By coordinating and examining the projections on the reduced dimensions by
      both the genes and the time-course experiments, we are able to identify important
      genes and time-course patterns and make inferences on their biological relevance.
      Using the sample replicates, we propose a bootstrap procedure for inferring the
      significance of contributions on the leading dimensions by both the time-course
      experiments and the genes. Striking differences in the time-course patterns in
      the normal controls and diabetes patients have been revealed. In addition, the
      method also identifies genes that display similar or comparable time-course
      expression patterns shared by both the cases and the controls. We conclude that
      our correspondence analysis based approach can be a useful tool for analyzing
      high dimensional microarray data collected in clinical investigations.

PMID- 15488750
TI  - Mapping high-dimensional data onto a relative distance plane--an exact method for
      visualizing and characterizing high-dimensional patterns.
AB  - We introduce a distance (similarity)-based mapping for the visualization of high
      dimensional patterns and their relative relationships. The mapping preserves
      exactly the original distances between points with respect to any two reference
      patterns in a special two-dimensional coordinate system, the relative distance
      plane (RDP). As only a single calculation of a distance matrix is required, this
      method is computationally efficient, an essential requirement for any exploratory
      data analysis. The data visualization afforded by this representation permits a
      rapid assessment of class pattern distributions. In particular, we can determine
      with a simple statistical test whether both training and validation sets of a 2
      class, high-dimensional dataset derive from the same class distributions. We can
      explore any dataset in detail by identifying the subset of reference pairs whose
      members belong to different classes, cycling through this subset, and for each
      pair, mapping the remaining patterns. These multiple viewpoints facilitate the
      identification and confirmation of outliers. We demonstrate the effectiveness of
      this method on several complex biomedical datasets. Because of its efficiency,
      effectiveness, and versatility, one may use the RDP representation as an initial,
      data mining exploration that precedes classification by some classifier. Once
      final enhancements to the RDP mapping software are completed, we plan to make it
      freely available to researchers.

PMID- 15488751
TI  - Multivariate image analysis in biomedicine.
AB  - In recent years, multivariate imaging techniques are developed and applied in
      biomedical research in an increasing degree. In research projects and in clinical
      studies as well m-dimensional multivariate images (MVI) are recorded and stored
      to databases for a subsequent analysis. The complexity of the m-dimensional data
      and the growing number of high throughput applications call for new strategies
      for the application of image processing and data mining to support the direct
      interactive analysis by human experts. This article provides an overview of
      proposed approaches for MVI analysis in biomedicine. After summarizing the
      biomedical MVI techniques the two level framework for MVI analysis is
      illustrated. Following this framework, the state-of-the-art solutions from the
      fields of image processing and data mining are reviewed and discussed.
      Motivations for MVI data mining in biology and medicine are characterized,
      followed by an overview of graphical and auditory approaches for interactive data
      exploration. The paper concludes with summarizing open problems in MVI analysis
      and remarks upon the future development of biomedical MVI analysis.

PMID- 15488752
TI  - Vascular frontiers without borders: multifaceted roles of platelet-derived growth
      factor (PDGF) in supporting postnatal angiogenesis and lymphangiogenesis.
AB  - The platelet-derived growth factor (PDGF) family of growth factors, which
      primarily serves the function of stabilizing vascular networks, has now been
      shown to play a role in promoting tumor lymphangiogenesis. PDGF-BB, independent
      of VEGFR-3 signaling, induces tumor growth and metastasis in part through
      supporting lymphangiogenesis. These data suggest that targeting the PDGF/PDGF
      receptor signaling pathway will provide a novel strategy to block tumor
      neoangiogenesis and lymphangiogenesis, thereby inhibiting tumor growth and
      metastasis.

PMID- 15488753
TI  - Antagonism of Myc functions by Arf.
AB  - The Arf-Mdm2-p53 tumor suppressor pathway is activated by sustained
      hyperproliferative signals emanating from oncoproteins such as Myc. A recent
      study reveals a novel level of feedback control, whereby induced p19(Arf) binds
      to Myc and blocks cell proliferation by selectively impairing its transactivation
      functions.

PMID- 15488754
TI  - Guilty as charged: B-RAF is a human oncogene.
AB  - RAF proteins are components of a conserved signaling pathway that regulates
      cellular responses to extracellular signals. Despite over 20 years of research
      into the regulation and function of the RAF proteins, it was only realized
      recently that the B-RAF isoform is mutated at a high frequency in human cancer.
      Here we review the rapid progress made in our understanding of B-RAF as an
      oncogene and of its role in cancer.

PMID- 15488755
TI  - The convergence of cancer prevention and therapy in early-phase clinical drug
      development.
AB  - After decades of separate but not equal drug development, prevention and therapy
      are beginning to converge at the level of early-phase clinical testing. This
      highly beneficial convergence is due to spectacular molecular advances in our
      understanding of neoplasia (both cancer and precancer), cancer risk and
      prognosis, and the mechanisms by which novel drugs with less toxicity and more
      cytostatic activity profiles target specific molecular events to suppress
      malignant and premalignant cells. The future full convergence of prevention
      therapy drug development (aided by technological advances, such as in molecular
      imaging) promises to hasten the progress of oncology in reducing the public
      health impact of the major cancers.

PMID- 15488756
TI  - Focus on hereditary endocrine neoplasia.

PMID- 15488757
TI  - PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis.
AB  - Cancer metastases are commonly found in the lymphatic system. Like tumor blood
      angiogenesis, stimulation of tumor lymphangiogenesis may require the interplay of
      several tumor-derived growth factors. Here we report that members of the PDGF
      family act as lymphangiogenic factors. In vitro, PDGF-BB stimulated MAP kinase
      activity and cell motility of isolated lymphatic endothelial cells. In vivo, PDGF
      BB potently induced growth of lymphatic vessels. Expression of PDGF-BB in murine
      fibrosarcoma cells induced tumor lymphangiogenesis, leading to enhanced
      metastasis in lymph nodes. These data demonstrate that PDGF-BB is an important
      growth factor contributing to lymphatic metastasis. Thus, blockage of PDGF
      induced lymphangiogenesis may provide a novel approach for prevention and
      treatment of lymphatic metastasis.

PMID- 15488758
TI  - TrkA alternative splicing: a regulated tumor-promoting switch in human
      neuroblastoma.
AB  - We identify a novel alternative TrkA splice variant, TrkAIII, with deletion of
      exons 6, 7, and 9 and functional extracellular IG-C1 and N-glycosylation domains,
      that exhibits expression restricted to undifferentiated early neural progenitors,
      human neuroblastomas (NBs), and a subset of other neural crest-derived tumors.
      This NGF-unresponsive isoform is oncogenic in NIH3T3 cells and promotes
      tumorigenic NB cell behavior in vitro and in vivo (cell survival, xenograft
      growth, angiogenesis) resulting from spontaneous tyrosine kinase activity and
      IP3K/Akt/NF-kappaB but not Ras/MAPK signaling. TrkAIII antagonizes NGF/TrkAI
      signaling, which is responsible for NB growth arrest and differentiation through
      Ras/MAPK, and its expression is promoted by hypoxia at the expense of NGF
      responsive receptors, providing a mechanism for converting NGF/TrkA/Ras/MAPK
      antioncogenic signals to TrkAIII/IP3K/Akt/NF-kappaB tumor-promoting signals
      during tumor progression.

PMID- 15488759
TI  - Distinct effects on gene expression of chemical and genetic manipulation of the
      cancer epigenome revealed by a multimodality approach.
AB  - We tested the hypothesis that the effects on gene expression of altered DNA
      methylation by 5-aza-2'-deoxycytidine (5-aza-CdR) and genetic (DNMT knockout)
      manipulation of DNA are similar, and distinct from Trichostatin A (TSA)-induced
      chromatin decondensation. Surprisingly, the effects of 5-aza-CdR were more
      similar to those of TSA than to DNMT1, DNMT3B, or double DNMT somatic cell
      knockout. Furthermore, the effects of 5-aza-CdR were similar at one and five days
      exposure, suggesting active demethylation or direct influence of both drugs on
      the stability of methylation and/or chromatin marks. Agents that induce gene
      activation through hypomethylation may have unintended consequences, since nearly
      as many genes were downregulated as upregulated after demethylation. In addition,
      a 75 kb cluster of metallothionein genes was coordinately regulated.

PMID- 15488760
TI  - Absence of telomerase and shortened telomeres have minimal effects on skin and
      pancreatic carcinogenesis elicited by viral oncogenes.
AB  - The telomere-stabilizing enzyme telomerase is induced in tumors and functionally
      associated with unlimited replicative potential. To further explore its
      necessity, transgenic mice expressing SV40 or HPV16 oncogenes, which elicit
      carcinomas in pancreas and skin, respectively, were rendered telomerase
      deficient. Absence of telomerase had minimal impact on tumorigenesis, even in
      terc(-/-) generations (G5-7) exhibiting shortened telomeres and phenotypic
      abnormalities in multiple organs. Analyses of chromosomal aberrations were not
      indicative of telomere dysfunction or increased genomic instability in tumors.
      Quantitative image analysis of telomere repeat intensities comparing biopsies of
      skin hyperplasia, dysplasia, and carcinoma revealed that telomere numbers and
      relative lengths were maintained during progression, implicating a means for
      preserving telomere repeats and functionality in the absence of telomerase.

PMID- 15488761
TI  - Epigenetic and genetic loss of Hic1 function accentuates the role of p53 in
      tumorigenesis.
AB  - The gene hypermethylated in cancer 1 (HIC1) is epigenetically inactivated, but
      not mutated, in cancer. Here we show that cooperative loss of Hic1 with p53, but
      not INK4a, yields distinct tumor phenotypes in mice. Germline deletion of one
      allele of each gene on the opposite chromosome yields breast and ovarian
      carcinomas and metastatic osteosarcomas with epigenetic inactivation of the wild
      type Hic1 allele. Germline deletion of the two genes on the same chromosome
      results in earlier appearance and increased prevalence and aggressiveness of
      osteosarcomas with genetic deletion of both wild-type genes. In human
      osteosarcomas, hypermethylation of HIC1 is frequent only in tumors with p53
      mutations. Our results indicate the importance of genes altered only through
      epigenetic mechanisms in cancer progression in conjunction with genetically
      modified tumor suppressor genes.

PMID- 15488763
TI  - Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host
      directly promotes tumor angiogenesis.
AB  - We demonstrate a novel tumor-promoting role of myeloid immune suppressor
      Gr+CD11b+ cells, which are evident in cancer patients and tumor-bearing animals.
      These cells constitute approximately 5% of total cells in tumors. Tumors
      coinjected with Gr+CD11b+ cells exhibited increased vascular density, vascular
      maturation, and decreased necrosis. These immune cells produce high levels of
      MMP9. Deletion of MMP9 in these cells completely abolishes their tumor-promoting
      ability. Gr+CD11b+ cells were also found to directly incorporate into tumor
      endothelium. Consistent with this observation, Gr+CD11b+ cells acquire
      endothelial cell (EC) properties in tumor microenvironment and proangiogenic
      culture conditions. Our data provide evidence that Gr+CD11b+ cells of immune
      origin induced by tumors directly contribute to tumor growth and vascularization
      by producing MMP9 and differentiating into ECs.

PMID- 15488762
TI  - APRIL promotes B-1 cell-associated neoplasm.
AB  - A tumor-supporting role for the TNF-like ligand APRIL has been suggested. Here we
      describe that 9- to 12-month-old APRIL transgenic mice develop lymphoid tumors
      that originate from expansion of the peritoneal B-1 B cell population. Aging
      APRIL transgenic mice develop progressive hyperplasia in mesenteric lymph nodes
      and Peyer's patches, disorganization of affected lymphoid tissues, mucosal and
      capsular infiltration, and eventual tumor cell infiltration into nonlymphoid
      tissues such as kidney and liver. We detected significantly increased APRIL
      levels in sera of B cell chronic lymphoid leukemia (B-CLL) patients, indicating
      that APRIL promotes onset of B-1-associated neoplasms and that APRIL antagonism
      may provide a therapeutic strategy to treat B-CLL patients.

PMID- 15488764
TI  - Effect of hydrostatic pressure on conformational changes of canine milk lysozyme
      between the native, molten globule, and unfolded states.
AB  - The effect of pressure on the unfolding of the native (N) and molten globule (MG)
      state of canine milk lysozyme (CML) was examined using ultraviolet (UV)
      spectroscopy at pH 4.5 and 2.0, respectively. It appeared that the thermally
      induced unfolding was promoted by the increase of pressure from atmospheric to
      100 MPa, which indicates that both the N and MG states of CML unfolded with the
      decrease of the partial molar volume change (DeltaV). The volume changes needed
      for unfolding were estimated from the free energy change vs. pressure plots, and
      these volume changes became less negative from 20 to 60 degrees C. The DeltaV
      values at 25 degrees C were obtained for the N-MG (-46 cm3/mol) and MG-unfolded
      state (U) transition (-40 cm3/mol). With regards to the MG-U transition, this
      value is contrastive to that of bovine alpha-lactalbumin (BLA) (0.9 cm3/mol),
      which is homologous to CML. Previous studies revealed that the MG state of CML
      was significantly more stable, and closer to the N state in structure, than that
      of BLA. In contrast to the swollen hydrophobic core of the MG state of BLA, our
      results suggest that the MG state of CML possesses a tightly packed hydrophobic
      core into which water molecules cannot penetrate.

PMID- 15488765
TI  - Evaluation of riboflavin binding protein domain interaction using differential
      scanning calorimetry.
AB  - Riboflavin binding (or carrier) protein (RfBP) is a monomeric, two-domain
      protein, originally purified from hens' egg white. RfBP contains nine disulfide
      bridges; as a result, the protein forms a compact structure and undergoes
      reversible three-state thermal denaturation. This was demonstrated using a
      differential scanning calorimetry (DSC) method [Wasylewski M. (2000) J. Prot.
      Chem. 19(6), 523-528]. It has been shown that the RfBP complex with riboflavin
      denaturates in a three-state process which may be attributed to sequential
      unfolding of the RfBP domains. In case of apo RfBP, the ligand binding domain
      denaturates at a lower temperature than the C-terminal domain. Ligand binding
      greatly enhances the thermostability of the N-terminal domain, whereas the C
      terminal domain thermostability is only slightly affected and, in case of the
      examined holo RfBPs, the denaturation peaks of both domains merge or cross over.
      The magnitude of the changes depends on ligand structure. A detailed study of
      protein concentration effects carried out in this work allowed to estimate not
      only the thermostability of both domains but also the strength of domain
      interactions. The DeltaCp, of denaturation was found for C-terminus and N
      terminus of RfBP-riboflavin complex to amount to 2.5 and -1.9 kcal mol(-1),
      respectively. The calculated domain interaction free energy, DeltaGCN, was
      estimated to be approximately -1580 cal mol(-1) at 67.0 degrees C. This value
      indicates that the interdomain interaction is of medium strength.

PMID- 15488766
TI  - Using LC-MS with de novo software to fully characterize the multiple methylations
      of lysine residues in a recombinant fragment of an outer membrane protein from a
      virulent strain of Rickettsia prowazekii.
AB  - The outer membrane protein B (OmpB) of the typhus group rickettsiae is an
      immunodominant antigen and has been shown to provide protection against typhus in
      animal models. Consequently, OmpB is currently being considered as a potential
      rickettsiae vaccine candidate to be used in humans. The OmpB from virulent
      strains are heavily methylated while the attenuated strains are hypomethylated.
      Western blot analysis of partially digested OmpB revealed that one of the
      reactive fragments was located at the N-terminus (fragment A, aa 33-272).
      Recently, we have over expressed, purified, and chemically methylated the
      recombinant fragment A from Rickettsia prowazekii (Ap). The methylated Ap was
      thoroughly characterized by LC/MS/MS on the ProteomeX workstation. The protein
      sequence of Ap with and without methylation was 87.7% and 100% identified,
      respectively. This high sequence coverage enabled us to determine the sites and
      extent of methylation on the lysine residues in Ap. All the lysine residues
      except the C-terminus lysine were either mono-, di- or tri-methylated. In
      addition, carbamylation on the N-terminus glycine was identified using a
      combination of denovo sequencing (DeNovoX) and the pattern recognition (SALSA)
      program with accurate mass measurement. We demonstrated that the use of peptide
      identification (SEQUEST) in combination with SALSA and denovo sequencing provided
      a useful means to characterize the sequence and posttranslational modifications
      of given proteins.

PMID- 15488767
TI  - Temperature dependence of NO binding modes in human neuroglobin.
AB  - Both the ferrous and ferric forms of wild-type neuroglobin are found to be
      hexacoordinated with axial ligation of the F8-His and E7-His. Rapidly growing
      Escherichia coli cell cultures with low O2 concentration generate nitric oxide
      (NO). Combined electron paramagnetic resonance (EPR) and optical measurements
      show that wild-type human recombinant neuroglobin, overexpressed in such E. coli
      cells, still favors the F8His-Fe2+ -E7His conformation, whereby only a small
      fraction of the protein binds NO. Upon mutation of the E7-His to Leu and Gln, the
      competition with the distal histidine disappears and the nitrosyl ferrous form is
      readily observed. At low temperature, the EPR spectra of the NO-ligated Ngb
      proteins consist of contributions from two geometrically different NO-heme
      conformations. In combination with EPR data of vertebrate hemoglobins and
      myoglobins, the temperature dependence of the EPR spectra of the NO adducts of
      ferrous hNgb and its E7-mutants proves a strong stabilization of one isomer by
      the E7-histidine in wt hNgb. It is shown that this is not related to the polarity
      of histidine, but to its specific binding characteristics.

PMID- 15488768
TI  - NMR structure of the C-terminal domain of SecA in the free state.
AB  - SecA is an integral component of the prokaryotic Sec preprotein secretory
      translocase system. We report here the solution NMR structure of a fragment
      corresponding to the C-terminal domain of Escherichia coli SecA. In the presence
      of Zn2+, the fragment adopts a shortened version of the classic betabetaalpha
      zinc finger fold. The isolated C-terminal domain shows substantial differences
      from the X-ray structure of a homologous SecA domain bound to the chaperone-like
      cofactor SecB. The differences between the structures of the free and bound forms
      suggest that binding to SecB causes a perturbation of the C-terminal domain's
      intrinsically favored betabetaalpha fold.

PMID- 15488769
TI  - Complex of sialoadhesin with a glycopeptide ligand.
AB  - Sialoadhesin is a sialic acid-binding immunoglobulin-like lectin (Siglec),
      expressed on subsets of macrophages. It is a model system for Siglec receptor
      mediated cell surface interactions through binding of sialylated glycoconjugates.
      The N-terminal sialoadhesin domain can mediate sialic acid-binding on its own.
      The structure of this domain has been determined in complex with a sialic acid
      containing heptapeptide, (Ala-Gly-His-Thr(Neu5Ac)-Trp-Gly-His). The affinity of
      sialoadhesin for this ligand is four times higher than the affinity for the
      natural linkage 2,3'-sialyllactose. The structure of the glycopeptide complex
      suggests strategies for ligand optimization and provides possible explanations
      for the observed differences in specificities among the Siglecs.

PMID- 15488770
TI  - Fluorescence spectroscopic characterization of Humicola lanuginosa lipase
      dissolved in its substrate.
AB  - The conformational dynamics of Humicola lanuginosa lipases (HLL) and its three
      mutants were investigated by steady state and time-resolved fluorescence
      spectroscopy in two different media, aqueous buffer and the substrate triacetin.
      The fluorescence of the four Trps of the wild-type HLL (wt) reports on the global
      changes of the whole lipase molecule. In order to monitor conformational changes
      specifically in the alpha-helical surface loop, the so-called 'lid' of HLL
      comprised of residues 86-93, the single Trp mutant W89m (W117F, W221H, W260H) was
      employed. Mutants W89L and W89mN33Q (W117F, W221H, W260H, N33Q) were used to
      survey the impact of Trp89 and mannose residues, respectively. Based on the data
      obtained, the following conclusions can be drawn. (i) HLL adapts the 'open'
      conformation in triacetin, with the alpha-helical surface loop moving so as to
      expose the active site. (ii) Trp89 contained in the lid plays an unprecedently
      important role in the structural stability of HLL. (iii) In triacetin, but not in
      the buffer, the motion of the Trp89 side chain becomes distinguishable from the
      motion of the lid. (iv) The carbohydrate moiety at Asn33 has only minor effects
      on the dynamics of Trp89 in the lid as judged from the fluorescence
      characteristics of the latter residue.

PMID- 15488771
TI  - A calpain-like proteolytic activity produces the limited cleavage at the N
      terminal regulatory domain of rabbit skeletal muscle AMP deaminase: evidence of a
      protective molecular mechanism.
AB  - On storage at 4 degrees C, rabbit skeletal muscle AMP deaminase undergoes limited
      proteolysis with the conversion of the native 85-kDa enzyme subunit to a 75-kDa
      core that is resistant to further proteolysis. Further studies have shown that
      limited proteolysis of AMP deaminase with trypsin, removing the 95-residue N
      terminal fragment, converts the native enzyme to a species that exhibits
      hyperbolic kinetics even at low K+ concentration. The results of this report show
      that a 21-residue synthetic peptide, when incubated with the purified enzyme, is
      cleaved with a specificity identical to that reported for ubiquitous calpains. In
      addition, the cleavage of a specific fluorogenic peptide substrate by rabbit m
      calpain is inhibited by a synthetic peptide that corresponds to residues 10-17 of
      rabbit skeletal muscle AMP deaminase; this peptide contains a sequence (K-E-L-D-D
      A) that is present in the fourth subdomain A of rabbit calpastatin, suggesting
      that the N-terminus of AMP deaminase shares with calpastatin a regulatory
      sequence that might exert a protective role against the fragmentation-induced
      activation of AMP deaminase. These observations suggest that a calpain-like
      proteinase present in muscle removes from AMP deaminase a domain that holds the
      enzyme in an inactive conformation and which also contains a regulatory region
      that protects against unregulated proteolysis. We conclude that proteolysis of
      AMP deaminase is the basis of the large ammonia accumulation that occurs in
      skeletal muscle subjected to strong tetanic contraction or passing into rigor
      mortis.

PMID- 15488772
TI  - Kinetic and equilibrium characterization of the interaction between bovine
      trypsin and I-ovalbumin.
AB  - Serpins are a superfamily of structurally linked proteins with interesting
      functional properties. Most serpins act as proteinase suicide inhibitors and play
      a key role in a number of physiological processes. Structural flexibility
      properties make serpins extremely available to conformational transitions, often
      causing changes in protein function. Ovalbumin is a member of the serpin family
      that is not able to inhibit serine proteinases in its native form. In contrast, I
      ovalbumin, the product of a heating transition, is a potent reversible serine
      proteinase inhibitor. In this paper, a detailed equilibrium and kinetic
      characterization of the interaction between the serpin ovalbumin and bovine
      trypsin, using a resonant mirror technique, is reported. This methodology
      revealed that the high affinity interaction between the two binding partners is
      characterized by high kinetic association constants and low kinetic dissociation
      constants. The modulation exerted by protons in solution, examined taking into
      account structural motifs characterizing the binding interface between the two
      macromolecules, suggests an interaction reminiscent of that observed for the
      binding of other serine proteases to their ligands.

PMID- 15488773
TI  - An archaeal histone-like protein as an efficient DNA carrier in gene transfer.
AB  - HPhA, a recombinant histone-like protein from Pyrococcus horikoshii OT3 strain,
      has compacting activity with DNA as previously reported. The extreme stability
      and DNA packaging activity of the HPhA make it a candidate as a DNA carrier.
      Here, the plasmid DNA-HPhA complexes were fully characterized by gel retardation
      assay and DNase resistance assay. It was further proved that HPhA has in vitro
      DNA transfection activity. HPhA-mediated transfection efficiency was dependent on
      the mass ratio of HPhA to DNA, the incubation time and the presence of calcium. A
      protocol for HPhA-mediated transfection in vitro was established to improve
      transfection efficiency. The optimal mass ratio of HPhA to DNA was 6:1, and the
      incubation time required for the DNA-HPhA complex to be in contact with the cell
      was 4 h. In addition, the presence of 2 mM CaCl2 in the cell culture medium was
      required for efficient transfection. Serum did not show inhibition of HPhA
      mediated transfection. Most importantly, the cytotoxicity of HPhA is lower than
      that of commonly used cationic liposome-based gene delivery systems, and HPhA
      mediated transfection in NIH 3T3, HEK 293, HL-7702, HepG2 and Cos 7 cell lines in
      vitro has a higher efficiency and reproducibility. These results demonstrate that
      the HPhA is a new, potentially widely applicable and highly efficient gene
      carrier.

PMID- 15488774
TI  - Basic amino acid residues in the beta-structure region contribute, but not
      critically, to presynaptic neurotoxicity of ammodytoxin A.
AB  - The molecular mechanism of action of presynaptically toxic secreted
      phospholipases A2 (sPLA2s) isolated from snake venoms is not completely
      understood. It has been proposed that the positive charge in the beta-structure
      region is important for their toxic activity. To test this hypothesis, we
      characterised several mutants of ammodytoxin A (AtxA) possessing substitution of
      all five basic residues in this region. The mutations had relatively little
      influence on the catalytic activity of AtxA, either on charge-neutral or anionic
      phospholipid vesicles. An exception was R72 when replaced by a hydrophobic
      (higher activity) or an acidic (lower activity) residue. Lethal potencies of the
      eight single site mutants were up to four times lower than that of the wild-type,
      whereas the triple mutant (K74S/H76S/R77L) was 13-fold less toxic. The
      substitutions also lowered the affinity of the toxin, slightly to moderately, for
      the neuronal receptors R25 and R180. Interaction with calmodulin was only
      slightly affected by substitutions of K86, more by those of the K74/H76/R77
      cluster and most by those of R72 (up to 11-fold lower binding affinity). The
      results clearly indicate that the basic amino acid residues in the beta-region of
      AtxA contribute to, but are not necessary for, its neurotoxic effect.

PMID- 15488775
TI  - The effect of lens edge design versus anterior capsule overlap on posterior
      capsule opacification.
AB  - PURPOSE: To determine whether lens edge design or anterior capsule overlap on the
      intraocular lens (IOL) has greater effect on posterior capsule opacification
      (PCO). DESIGN: Retrospective cohort clinical study. METHODS: Retrospective.
      SETTING: Academic clinical practice. PATIENT POPULATION: The patient population
      consisted of 259 uncomplicated surgical patients (259 eyes) with no confounding
      comorbidity and at least 1 year of follow-up after surgical placement of a
      silicone or hydrophobic acrylic lens. OBSERVATION PROCEDURES: Digital
      retroilluminated photographs were taken to ascertain PCO, anterior capsular
      opacification (ACO), previous neodymium:YAG capsulotomy and degree of anterior
      capsule overlap on the IOL optic. MAIN OUTCOME MEASURES: PCO, ACO, YAG
      capsulotomy rate, and anterior capsule overlap on the IOL optic. RESULTS: One
      hundred forty-eight digital images (74 silicone and 74 acrylic) were measurable
      for both anterior capsule overlap and PCO. Complete 360 degrees of anterior
      capsule overlap on the IOL was associated with decreased PCO (P = <.001). A
      significant negative correlation was found between the degree of anterior capsule
      overlap and PCO (P = <.001). Evaluation of PCO, and YAG capsulotomy rates were
      similar between acrylic and silicone lenses. Minimal anterior capsule overlap may
      also be associated with PCO prevention. CONCLUSIONS: Implanting a lens with
      complete anterior capsule overlap on the IOL was found to significantly reduce
      PCO, which advantage appeared to be greater than PCO prevention by a truncated,
      sharp edge IOL design.

PMID- 15488776
TI  - Quality of life in keratoconus.
AB  - PURPOSE: Keratoconus is a chronic, noninflammatory disease of the cornea with
      onset in early adulthood. As these years are important to financial and social
      health, keratoconus may have more severe impact on quality of life than would be
      expected given its clinical severity. We examined the vision-related quality of
      life of patients in the Collaborative Longitudinal Evaluation of Keratoconus
      (CLEK) Study. DESIGN: Cross-sectional study. METHODS: The National Eye Institute
      Visual Function Questionnaire (NEI-VFQ) was administered to 1166 CLEK Study
      patients at their first annual follow-up examination. Associations between
      clinical and demographic factors and NEI-VFQ scale scores were evaluated.
      RESULTS: Binocular entrance visual acuity worse than 20/40 was associated with
      lower quality of life scores on all scales except General Health and Ocular Pain.
      A steep keratometric reading (average of both eyes) >52 diopters (D) was
      associated with lower scores on the Mental Health, Role Difficulty, Driving,
      Dependency, and Ocular Pain scales. Scores for CLEK patients on all scales were
      between patients with category 3 and category 4 age-related macular degeneration
      (AMD) except General Health, which was better than AMD patients, and Ocular Pain,
      which was worse than AMD patients. CONCLUSIONS: Keratoconus is a disease of
      relatively low prevalence that rarely results in blindness, but because it
      affects young adults, the magnitude of its public health impact is
      disproportionate to its prevalence and clinical severity.

PMID- 15488777
TI  - The effect of vitreous presentation during extracapsular cataract surgery on the
      postoperative visual acuity at one year.
AB  - PURPOSE: The purpose of this study was to determine the effects that vitreous
      presentation (VP) during extracapsular cataract surgery has on patients' 1-year
      postoperative vision. DESIGN: The study was a prospective, long-term, clinical
      trial. METHODS: The study took place at 19 Department of Veterans Affairs medical
      centers. Patients having VP during cataract surgery and receiving a posterior
      chamber (PC) intraocular lens (IOL) (230 patients) were prospectively compared
      with a 5% random sample of nonvitreous presentation (NVP) cataract surgery
      patients (521 patients). Best-corrected visual acuity (BCVA) at 1 year was
      obtained by a masked, certified examiner. RESULTS: There was no statistical
      difference (P = .089) between the VP patients receiving PC IOL and the NVP
      patients in percentage of patients having BCVA of 20/40 or better at 1 year
      (91.1% vs 94.9%). There were significantly more PC IOL VP patients than NVP
      patients with BCVA of 20/50 or worse at some time during the first postoperative
      year (21.6% vs 10.9%; P = .0003), significantly fewer with BCVA of 20/20 or
      better at 1 year (27.8% vs 38.8%; P = .013), and significantly more with cystoid
      macular edema (11.5% vs 3.6%; P = .0002), retinal detachment (4.3% vs 0.2%; P =
      .0002), and uveitis (3.4% vs 0.6%; P = .012). The NVP patients rated their vision
      as very good or excellent significantly more often than the VP patients (71% vs
      58%; P = .025). CONCLUSIONS: Vitreous presentation during extracapsular cataract
      surgery leads to somewhat worse overall outcomes in patients, although the
      majority of patients with VP do reasonably well.

PMID- 15488778
TI  - Analysis of melanoma cell type in uveal melanoma following treatment failure.
AB  - PURPOSE: To determine whether an increase (or progression) in the degree of
      malignancy according to cytologic or histopathologic criteria corresponded with
      failure of intraocular melanoma control. DESIGN: Retrospective case control study
      from a single institution. METHODS: Uveal melanoma patients had either fine
      needle aspiration biopsy followed by irradiation and later enucleation or an
      eyewall resection followed by enucleation. The observation procedures were serial
      histology or cytopathology and histology, reanalyzed in a masked manner. The main
      outcome measures were change in the predominant tumor cell type, local tumor
      control, and metastases. RESULTS: There was not a significant correlation between
      a change in melanoma cell type and failure to control intraocular melanoma.
      Similarly, the latency between treatment and enucleation was actually less (but
      not statistically so) in tumors that showed no increase in melanoma malignancy
      cell type compared with those that had a more malignant cell type on serial
      examination. CONCLUSIONS: There was no correlation between a change to more a
      malignant cell type and local control failure in patients treated either with
      radiation or eyewall resection for uveal melanoma.

PMID- 15488779
TI  - Corneal pharmacokinetics of topically applied azithromycin and clarithromycin.
AB  - PURPOSE: To determine corneal levels of topically administered azithromycin and
      clarithromycin in a rabbit model. DESIGN: Experimental animal study. METHODS:
      Corneas of New Zealand albino rabbits were treated with topical azithromycin (2
      mg/ml or 4 mg/ml) or clarithromycin (10 mg/ml). Topical azithromycin was prepared
      from an intravenous solution and topical clarithromycin from a suspension for
      oral use. All rabbits received one drop every 2 hours on the right eye. Groups of
      rabbits were treated for the following intervals: 6, 12, 24, and 48 hours (four
      rabbits for each combination of time point, drug, and dose). Corneal tissue was
      removed 1 hour after the last application. To investigate stability of tissue
      azithromycin levels, an additional group of four rabbits was treated for 24
      hours, but corneal tissue was not removed until 24 hours later. Samples were
      homogenized, and drug concentrations were measured using high-pressure liquid
      chromatography (HPLC) analysis and bioactivity assay. RESULTS: Corneal
      concentrations of azithromycin increased with drug dosage and duration of
      application. Rabbits treated with azithromycin tolerated the drug well without
      signs of irritation. Clarithromycin was undetectable in corneal tissue by HPLC
      and bioactivity assay for all rabbits. Some rabbits treated with clarithromycin
      had signs of ocular surface irritation. CONCLUSION: Measurable concentrations of
      azithromycin are achieved in corneal tissue after topical application in a rabbit
      model, and the drug is well tolerated. Azithromycin may be a useful antibiotic
      for the topical treatment of human corneal infections, but clarithromycin, in
      currently available formulations, may not be effective because of poor tissue
      penetration.

PMID- 15488780
TI  - The effect of cataract surgery on ocular levels of topical moxifloxacin.
AB  - PURPOSE: To investigate the effect of cataract surgery on the concentration of
      moxifloxacin in aqueous and vitreous humor after topical application. DESIGN:
      Prospective laboratory intervention using a rabbit model. METHODS: Following
      topical administration of 0.5% moxifloxacin, 60 minutes before surgery and
      immediately post cataract surgery, aqueous and vitreous humor were sampled at 30,
      60, and 120 minutes postsurgery. Moxifloxacin concentrations were determined by
      high-pressure liquid chromatography (HPLC). Mean tissue concentrations obtained
      in surgical eyes were compared with concentrations obtained in nonsurgical eyes.
      The potential effectiveness of moxifloxacin in providing prophylaxis against
      intracameral bacterial inoculation was investigated by comparing antibiotic
      concentrations to minimum inhibitory concentration (median MIC90) values for
      Staphylococcus aureus and Staphylococcus epidermidis. RESULTS: In surgical eyes,
      mean moxifloxacin concentrations in aqueous were 13.9, 16.2, and 12.2 microg/ml
      versus 25.3, 32.6, and 15.7 microg/ml in nonoperated eyes at 30, 60, and 120
      minutes, respectively. No statistically significant differences were found
      between surgical and nonsurgical eyes. In surgical eyes, mean moxifloxacin
      concentrations in vitreous were 66.8, 66.6, and 400.2 ng/ml versus 43.1, 199.8,
      and 54.4 ng/ml in nonoperated eyes at 30, 60, and 120 minutes, respectively.
      These differences were not statistically significant. CONCLUSIONS: There were no
      statistically significant differences in the penetration of topical moxifloxacin
      in eyes undergoing cataract surgery compared with unoperated eyes. A multiple
      drop schedule of moxifloxacin produced aqueous concentrations that were well
      above the MICs of even resistant strains of the most common organisms implicated
      in postcataract surgery endophthalmitis.

PMID- 15488782
TI  - Apolipoprotein E polymorphisms in Japanese patients with polypoidal choroidal
      vasculopathy and exudative age-related macular degeneration.
AB  - PURPOSE: To study the genotypes, allelic frequencies, and polymorphisms of
      apolipoprotein E (Apo E) in unrelated Japanese patients with polypoidal choroidal
      vasculopathy (PCV) or exudative age-related macular degeneration (AMD) and
      control subjects without macular degeneration. DESIGN: Cross-sectional study.
      METHODS: Blood samples from 225 subjects older than 50 years were used. The 225
      subjects included 58 patients with PCV, 85 with AMD, and 82 without macular
      degeneration. Coding exons of the Apo E gene were amplified by polymerase chain
      reaction, and the DNA sequences were determined by direct sequencing with an
      automated sequencer. RESULTS: Apo E epsilon3/epsilon3 was the most frequent
      genotype with a prevalence of 79.3% in PCV patients, 76.5% in AMD patients, and
      67.1% in the control subjects. However, the differences in the percentages were
      not statistically significant among the three groups. The most frequently found
      allele in the three groups was epsilon3. Patients with PCV and AMD were less
      likely to have epsilon2 and epsilon4 than the control subjects, but the
      differences were not statistically significant. Five minor Apo E single
      nucleotide polymorphisms, including epsilon5 and epsilon7, were found.
      CONCLUSION: Japanese patients with PCV and AMD were less likely to have epsilon2
      and epsilon4 polymorphisms, but the differences from the normals were not
      statistically significant for the Apo E genotypes and allelic frequencies.

PMID- 15488781
TI  - Intrasurgical plasmin enzyme in diabetic macular edema.
AB  - PURPOSE: To evaluate in a prospective study the efficacy of intrasurgical
      autologous plasmin enzyme (APE) in producing posterior vitreous detachment.
      DESIGN: Consecutive, interventional case series. METHODS: A group of 12 eyes of
      11 patients with diabetic macular edema secondary to posterior vitreous cortex
      contraction was considered. A quantity of 0.1- to 0.2-ml containing 0.8 to 1.2 IU
      of APE prepared by our Coagulation Service was injected into the vitreous body 25
      minutes before surgery. The efficacy of the APE was subjectively evaluated. A
      control group of 10 eyes with the same clinical characteristics underwent the
      same surgery without APE injection. Complete eye examinations, including optical
      coherence tomography, were performed on all patients before surgery and during
      the 1-year follow-up period. RESULTS: During surgery in the APE-treated group,
      the posterior vitreous cortex was judged adherent in three cases, partially
      detached in six cases, and totally detached in three cases. In two cases a
      complete collapse of the vitreous body was observed. During surgery in the non
      APE-treated group, the posterior vitreous cortex was judged still adherent in
      nine of 10 eyes and partially detached in 1 eye. Comparing the postoperative
      results between the APE-treated group and the non-APE-treated group, we found no
      significant differences in final postoperative retinal thickness (P = .2552),
      whereas we found a significant difference in final visual acuity (P = .0121).
      CONCLUSIONS: Autologous plasmin enzyme was useful in inducing a pharmacologic
      posterior vitreous detachment and in facilitating surgery. It did not seem to
      interfere with the final retinal thickness, and it ameliorates the final visual
      acuity.

PMID- 15488783
TI  - Macular translocation with chorioscleral outfolding: 2-year results.
AB  - PURPOSE: To evaluate the results of macular translocation with radial
      chorioscleral outfolding in patients with subfoveal choroidal neovascularization
      (CNV) and to identify factors associated with decreased postoperative visual
      acuity. DESIGN: Retrospective interventional case series. METHODS: Twenty-seven
      consecutive patients with surgically treated subfoveal CNV were operated on and
      followed for more than 2 years. Macular translocation with radial chorioscleral
      outfolding was performed using titanium clips. Surgical outcomes including visual
      acuity, foveal displacement, surgically induced astigmatism, and complications
      were recorded. Factors associated with decreased visual acuity postoperatively
      were identified by multiple logistic regression analysis. RESULTS: Foveal
      displacement ranged from 349 to 3391 (median, 1576) microm. Surgically induced
      astigmatism ranged from 0 to 3.0 (median, 0.5) diopters. Visual acuity after
      surgery improved in 19 of the 27 patients (70.4%; median, 5 lines), but in 14,
      final vision ultimately decreased from the best postoperative level. Final visual
      acuity improved from the preoperative level in 11 patients (40.7%), remained
      unchanged in seven (25.9%), and decreased in nine (33.3%). In our series, the
      mean preoperative vision was 20/174, the best postoperative visual acuity was
      20/74, and the mean final vision was 20/167. Factors associated with a decrease
      in postoperative visual acuity included the postoperative enlargement of CNV.
      CONCLUSION: Macular translocation with radial chorioscleral outfolding improved
      or stabilized the vision in 66.7% of patients with subfoveal CNV over the course
      of more than 2 years. Closing the CNV or preventing its further growth is
      required to maintain a better postoperative visual acuity.

PMID- 15488784
TI  - Macular pigment density and aging, assessed in the normal elderly and those with
      cataracts and age-related macular degeneration.
AB  - PURPOSE: Increasing evidence has linked retinal lutein and zeaxanthin (termed
      macular pigment, MP) to the risk of age-related macular degeneration (AMD).
      Currently, however, studies differ regarding the question of whether MP declines
      with age or age has an effect in patient populations being assessed. This study
      assessed MP across the lifespan with an emphasis on assessing MP in a cross
      section of elderly including those with lenticular or age-related macular
      degeneration, or both. DESIGN: Prospective, observational, cross-sectional study.
      METHODS:  SETTING: Institution. STUDY POPULATION: Cross-sectional study of
      normal, cataractous, and AMD subjects tested in Indianapolis, Indiana, including
      390 subjects, 22 with cataracts and 59 with age-related macular degeneration.
      OBSERVATIONAL PROCEDURE: MP density was measured with a one-degree diameter test
      field at 460 nm using a psychophysical method based on heterochromatic flicker
      photometry. MAIN OUTCOME MEASURES: MP optical density. RESULTS: MP does not
      appear to change as a function of age (r = +.04) when examining subjects across
      the lifespan (from 18-88 years). There was a slight tendency (slope = -.0027, r =
      -.11) for MP to decline when only the elderly subjects were considered, but this
      trend was not significant (P < .12) for any of the groups considered (normal,
      cataractous, or AMD). CONCLUSIONS: MP does not change significantly with age,
      even when elderly subjects with cataracts and AMD are considered. Using
      heterochromic flicker photometry, elderly subjects display a full range of MP
      density that is similar to young subjects.

PMID- 15488785
TI  - The use of a polyglactin suture in the lateral tarsal strip procedure.
AB  - PURPOSE: To evaluate the rate of recurrence of horizontal laxity or lid
      malposition and suture-related complications associated with the use of an
      absorbable suture in the lateral tarsal strip procedure. DESIGN: Prospective,
      interventional, consecutive case series. METHODS: A prospective study. SETTING:
      Institutional. PATIENT POPULATION: One hundred patients with horizontal lid
      laxity associated with ectropion or entropion. Patients with paralytic ectropion
      or ocular prostheses were excluded. INTERVENTION: One hundred and five lateral
      tarsal strip procedures were performed using a 6-0 polyglactin suture. These were
      combined with full-thickness skin grafts (34), internal (55) or external (23)
      retractor plications, and inverting sutures (4) as required to correct the lid
      malposition. MAIN OUTCOME MEASURES: Recurrence of horizontal laxity or lid
      malposition and suture related complications were the main outcome measures.
      Suture related wound infection was diagnosed clinically by the presence of pus
      associated with wound breakdown. RESULTS: One patient failed to reach 3-month
      follow-up and was excluded. There was one recurrence of horizontal laxity after a
      mean follow-up period of 9.1 months. Four patients developed lateral canthal
      wound infections, compared with none at the other operative sites. The 95%
      confidence intervals for infections in the tarsal strip procedure were 1.1% to
      9.6%, which were significantly greater than zero (P < .0001), the infection rate
      for the other procedures. CONCLUSION: A 6-0 absorbable suture may be used for the
      lateral tarsal strip and does not lead to a recurrence of horizontal laxity. It
      does not appear to reduce the wound infection rate associated with this
      procedure.

PMID- 15488786
TI  - Retinal nerve fiber layer thickness measurements with scanning laser polarimetry
      predict glaucomatous visual field loss.
AB  - PURPOSE: To assess whether baseline retinal nerve fiber layer (RNFL) measurements
      obtained with a scanning laser polarimeter, the GDx Nerve Fiber Analyzer, (Laser
      Diagnostic Technologies Inc., San Diego, California) are predictive of
      development of repeatable glaucomatous visual field damage in glaucoma suspect
      eyes. DESIGN: Cohort study. METHODS: Participants were recruited from the UCSD
      longitudinal Diagnostic Innovations in Glaucoma Study (DIGS). One eye from each
      of 160 glaucoma suspects with normal standard automated perimetry (SAP) visual
      fields at baseline was studied. Study eyes were divided into convert and
      nonconvert groups based on the development of three consecutive glaucomatous
      visual fields during follow-up. SLP parameters, IOP, vertical cup disk ratio,
      stereophotograph assessment as glaucoma or normal, corneal thickness, and visual
      field indices were included in univariate and multivariate Cox proportional
      hazards models to determine which SLP RNFL and ocular parameters were predictive
      of visual field conversion. RESULTS: Sixteen (10%) eyes developed repeatable
      visual field damage (converts) and 144 (90%) did not (nonconverts). Mean (95%CI)
      follow-up time until visual field conversion for convert eyes was 2.7 (1.7, 3.6)
      years. Mean total follow-up of nonconvert eyes was 3.8 (3.5, 4.1) years. Four out
      of thirteen examined baseline SLP parameters and baseline SAP Mean Deviation
      (MD), SAP Pattern Standard Deviation (PSD), and glaucomatous stereophotograph
      assessment were significant univariate predictors of visual field conversion. In
      multivariate models adjusted for age, IOP and CCT, SLP parameters inferior ratio,
      ellipse modulation, and UCSD linear discriminant function (LDF) were significant
      predictors of visual field conversion. When SAP PSD and stereophotograph
      assessment were also included in the multivariate model inferior ratio and UCSD
      LDF remained independently predictive of visual field loss. CONCLUSIONS: Thinner
      baseline SLP RNFL measurements were independent predictors of visual field
      damage. In addition to thinner SLP RNFL measurements, higher baseline SAP PSD,
      and baseline glaucomatous stereophotograph assessment each contributed to an
      increased risk of the development of abnormal visual fields in glaucoma suspect
      patients. SLP RNFL measurements were independently predictive of future visual
      loss even when age, IOP, CCT, vertical cup disk ratio, and SAP PSD were included
      in the model.

PMID- 15488787
TI  - Photodynamic therapy of subfoveal choroidal neovascularization in high myopia in
      a clinical setting: visual outcome in relation to age at treatment.
AB  - PURPOSE: To evaluate the visual outcome of patients with myopic subfoveal
      choroidal neovascularization (CNV) given photodynamic therapy (PDT) in a clinical
      setting, and to identify potential relation between the visual outcome and the
      age at treatment. DESIGN: Interventional case series. METHODS: Retrospective
      comparative study. SETTING: Outpatient ophthalmology clinic. PATIENTS: Twenty
      nine consecutive patients (30 eyes) with subfoveal CNV caused by pathologic
      myopia who were treated with verteporfin PDT from January 2000 to May 2003.
      INTERVENTION: All the patients received verteporfin PDT and were followed
      clinically and with fluorescein angiography (FA). Review of the medical records
      and angiograms was performed. Patients were divided into two groups by age, using
      the median age (60 years) as the cutoff. MAIN OUTCOME MEASURES: Visual acuity
      (VA) at the end of follow-up in the older-patient group compared with the younger
      patient group. RESULTS: The mean age was 63.1 years. Mean follow-up was 11.5
      months. Patients received a mean of 3.48 treatments. Mean VA improved in the
      younger group from 0.63 to 0.39 logMAR (P = .02, paired t test) and deteriorated
      in the older group from 0.71 to 0.99 logMAR (P = .03, paired t test). In the
      whole cohort, 33% of eyes lost 3 or more lines of Snellen best-corrected VA; in
      the older age group, 50% of eyes lost 3 or more lines, whereas in the younger age
      group, only 8% of eyes did so (P = .024, Fisher's exact test). CONCLUSIONS: In
      our consecutive case series, visual prognosis of myopic CNV after PDT was found
      to be influenced by age at treatment.

PMID- 15488788
TI  - Familial idiopathic macular hole.
AB  - PURPOSE: To report macular hole formation among siblings within four families.
      DESIGN: Observational case series. METHODS: Four families were identified who had
      macular holes among siblings from within three multiphysician tertiary-care
      referral retina practices. RESULTS: In the first family, two sisters in their
      seventh decade developed Stage 2 macular holes requiring surgical intervention;
      two male siblings were unaffected. In a second family, three of four siblings
      were affected, including one brother with a Stage 4 macular hole, one sister with
      a Stage 3 macular hole, and a third sister with a lamellar macular hole. In a
      third family, two siblings (one man, one woman) developed macular holes within 1
      year of each other. Three years later, the male sibling developed a macular hole
      in the fellow eye. In the last family, twin sisters developed macular holes
      (unilateral in one sister, bilateral in the other), and their deceased father may
      also have had bilateral macular holes. CONCLUSIONS: The occurrence of macular
      holes in these four sets of siblings suggests a possible genetic component in the
      formation of macular holes in these individuals.

PMID- 15488789
TI  - Evaluation of radial optic neurotomy for central retinal vein occlusion by
      indocyanine green videoangiography and image analysis.
AB  - PURPOSE: To evaluate the effects of radial optic neurotomy (RON) on retinal
      circulation in patients with central retinal vein occlusion (CRVO) by indocyanine
      green (ICG) videoangiography and a computer-assisted image analysis. DESIGN: An
      interventional case series. METHODS: RON was performed in 15 eyes of 15 patients
      with CRVO. Within 72 hours before the surgery and at 3 months after the surgery,
      ICG videoangiography was performed with a scanning laser ophthalmoscope, and the
      images were transferred to a computer. Two measurement points were selected, one
      on a main retinal artery close to the optic disk and the other on the
      corresponding retinal vein. At each point, fluorescence intensities were serially
      measured, and dye dilution curves were obtained. Retinal circulation times
      (DeltaT(50)) before and after the surgery were calculated. RESULTS: Mean
      preoperative DeltaT(50) was 6.46 +/- 1.36 seconds, and mean postoperative
      DeltaT(50) was 6.80 +/- 2.50 seconds. In 8 of 15 eyes, T(50) decreased by 6.8% to
      29.6% after the surgery. In the seven eyes that developed chorioretinal
      anastomosis (CRA) at the site of RON, DeltaT(50) decreased after the surgery. In
      contrast, DeltaT(50) decreased postoperatively in only one of the eight eyes
      without CRA. Best-corrected visual acuity improved significantly after the
      surgery in the group of eyes with improvement in DeltaT(50), but not in the group
      of eyes without improvement in DeltaT(50). CONCLUSIONS: Some degree of retinal
      circulation improvement occurred in approximately half of these eyes, which
      appears to be correlated with the development of CRA.

PMID- 15488790
TI  - Influence of wavefront aberration and corneal subepithelial haze on low-contrast
      visual acuity after photorefractive keratectomy.
AB  - PURPOSE: To assess low-contrast visual acuity (LCVA) after photorefractive
      keratectomy in relation to ocular higher-order wavefront aberration and corneal
      subepithelial haze. DESIGN: Prospective, cross-sectional analysis. METHODS:
      Photorefractive keratectomy was performed in 51 eyes of 27 subjects with myopic
      refractive error of -2.0 to -10.5 diopters. Ocular higher-order wavefront
      aberrations for a 4-mm pupil were measured using Topcon Hartmann-Shack wavefront
      aberrometer, and the extent of corneal subepithelial haze was quantified with
      Nidek TSPC-3 hazemeter before and 1 month after photorefractive keratectomy. Low
      contrast visual acuity was recorded with Vector Vision CSV-1000LanC10% chart.
      Total higher-order, third-order (coma-like), and fourth-order (spherical-like)
      aberrations of the eye were determined. The influence of wavefront aberration and
      corneal subepithelial haze on LCVA was analyzed. RESULTS: Total higher-order,
      third-order, and fourth-order aberrations significantly increased by surgery (P <
      .001, Wilcoxon signed rank test). Photorefractive keratectomy induced a
      significant increase in corneal haze (P < .01), but no case presented severe
      corneal haze (grade 3 or greater by Fantes grading). By surgery, LCVA was reduced
      significantly (P < .001). The logarithm of the minimal angle of resolution LCVA
      showed a significant correlation with total higher-order aberration (Spearman
      rank correlation coefficient, r(s) = 0.642, P < .0001). Both third-order (r(s) =
      0.618, P < .0001) and fourth-order aberrations (r(s) = 0.552, P < .0001) also
      significantly correlated with logarithm of the minimal angle of resolution LCVA.
      There was no correlation between the degree of corneal haze and logarithm of the
      minimal angle of resolution LCVA (r(s) = 0.094, P = .523). CONCLUSIONS: In eyes
      with mild to moderate corneal haze after photorefractive keratectomy,
      deterioration of LCVA is mainly attributable to increases in wavefront
      aberration, and not to corneal haze.

PMID- 15488791
TI  - Analysis of irises with a latanoprost-induced change in iris color.
AB  - PURPOSE: To study the histologic aspects of irises subjected to extended
      latanoprost treatment. DESIGN: Prospective, observer-masked study. METHODS: Iris
      biopsies of eyes treated with latanoprost were analyzed (all had a
      photographically documented increase in iris pigmentation) plus control eyes
      (untreated with prostanoids) using optical microscopy. PATIENT OR STUDY
      POPULATION: There were 14 study eyes treated with latanoprost and 8 untreated
      control eyes. MAIN OUTCOME MEASURE: The morphologic characteristics of the
      irises. RESULTS: The irises treated with latanoprost had an increased number of
      melanocytes with nuclear inclusions, granules of melanin in the vascular walls
      and the melanocytes and free granules in the stroma compared with control eyes (P
      = .001, P = .01, P = .004, P = .01, respectively, by the chi(2) test).
      CONCLUSIONS: Chronic therapy with latanoprost appears to induce more changes in
      the iris than a simple increase in the melanin content of the melanocytes.

PMID- 15488792
TI  - Human leukocyte antigen A29 subtypes associated with birdshot
      retinochoroidopathy.
AB  - PURPOSE: To determine whether birdshot retinochoroidopathy is associated with
      subtypes of the human leukocyte antigen (HLA)-A29 other than HLA-A*2902. DESIGN:
      Experimental study. METHODS: High-resolution DNA typing of HLA-A29 subtypes was
      performed on blood from 20 subjects with birdshot retinochoroidopathy using
      polymerase chain reaction-based typing methods. Results were compared with
      published controls. RESULTS: Four of 20 subjects (20%) had the HLA-A*2901 allele;
      two were homozygous for HLA-A*29, and both had the HLA-A*2901 and HLA-A*2902
      alleles. Among 18 subjects with only one HLA-A*29 allele, the HLA-A*2902 allele
      was found in 16 (89%) and the HLA-A*2901 allele was found in two (11%). No
      subject was found to have HLA-A*2903, HLA-A*2904, HLA-A*2905, or HLA-A*2906.
      CONCLUSIONS: Both HLA-A*2901 and HLA-A*2902 are associated with birdshot
      retinochoroidopathy. Our data do not support the previous suggestion that the HLA
      A29.1 serotype may be protective against development of birdshot
      retinochoroidopathy. Additional studies will be required to determine whether the
      other, less common subtypes are associated with the disease. HLA-A29 subtype
      testing is not required for the clinical evaluation of HLA-A29-positive patients
      with birdshot retinochoroidopathy.

PMID- 15488793
TI  - Posterior capsule opacification and YAG capsulotomy.

PMID- 15488794
TI  - CLEK study reports on the quality of life.

PMID- 15488795
TI  - Ocular side effects from herbal medicines and nutritional supplements.
AB  - PURPOSE: To review the more significant herbal and nutritional agents of clinical
      importance to ophthalmologists and describe the ocular side effects for each.
      World Health Organization (WHO) classification and guidelines for clinicians are
      provided. DESIGN: Retrospective observational case series. METHODS: A
      retrospective observational case series of reports of ocular side effects or
      systemic side effects from medications used for the eye from herbal medicines and
      nutritional supplements. Cases were collected from spontaneous reports submitted
      to the WHO, the Food and Drug Administration, and the National Registry of Drug
      Induced Ocular Side Effects. A review of the world's literature was performed to
      obtain additional case reports and insight into adverse ocular reactions. Data
      were collected on age, gender, duration of therapy, concomitant medications,
      dosage, and dechallenge and rechallenge results. RESULTS: The National Registry
      of Drug-Induced Ocular Side Effects received 263 spontaneous reports, in addition
      to 60 case reports from the literature. Canthaxanthine, chamomile, Datura,
      Echinacea purpurea, Ginkgo biloba, licorice, niacin, and vitamin A are all
      associated with clinically significant ocular side effects. CONCLUSION: Herbal
      medicines and nutritional supplements can cause ocular side effects. Clinicians
      need to recognize these adverse events, because a large segment of the population
      uses them, many times without the treating physician's knowledge.

PMID- 15488796
TI  - Infliximab for chronic cystoid macular edema associated with uveitis.
AB  - PURPOSE: To assess the efficacy of the anti-TNF monoclonal antibody infliximab in
      uveitis patients without clinically evident ocular inflammation and impaired
      visual acuity because of chronic cystoid macular edema (CME). DESIGN:
      Prospective, noncomparative, interventional case series. METHODS: Patients with
      refractory CME (14 eyes, mean duration of 14 months), associated with
      intermediate uveitis (n = 6), Adamantiades-Behcet disease (n = 2), adult-type
      vascular pseudotumor (n = 1), and HLAB27+-related uveitis (n = 1) received an
      intravenous infliximab infusion (5 mg/kg); five patients were retreated after 1
      month. RESULTS: Macular thickness, measured by ocular coherence tomography, was
      reduced from 428 +/- 138 microm to 219 +/- 51 microm at 2 months postbaseline (P
      = .0001), while visual acuity increased from 0.41 +/- 0.18 to 0.83 +/- 0.17 (P <
      .00001). Anatomic and functional improvement was sustained at 6 months in all. No
      ocular or extra-ocular side effects were noted. CONCLUSION: These promising
      results suggest that TNF may play an important pathogenetic role in chronic CME,
      thus, a controlled trial is warranted.

PMID- 15488797
TI  - Intracameral triamcinolone helps to visualize and remove the vitreous body in
      anterior chamber in cataract surgery.
AB  - AIM: To study the effects of intracameral injection of triamcinolone acetonide on
      visualizing and removing the vitreous body from the anterior chamber in cataract
      surgery. DESIGN: Observational case series. METHODS: Six eyes of six patients had
      the posterior capsule ruptured and the vitreous body prolapsed or incarcerated
      into the anterior chamber during cataract surgery. To visualize vitreous body,
      triamcinolone acetonide solution was injected into the anterior chamber and the
      vitreous body was resected. The intraoperative findings, results, and
      complications were evaluated. RESULTS: Vitreous body was well observed under
      surgical microscopy and was resected safely and completely. Minimum inflammation
      was observed postoperatively, and the patients obtained good visual acuity. No
      serious complications were found. One eye showed increased intraocular pressure
      (40 mm Hg), which was normalized by additional washing of the anterior chamber.
      CONCLUSIONS: Appropriate use of intracameral triamcinolone acetonide is
      beneficial to visualize and remove the vitreous body from the anterior chamber
      during cataract surgery, and sufficient washing of the anterior chamber is
      necessary to avoid complications.

PMID- 15488798
TI  - Ultrasound biomicroscopic analysis of iris profile changes with accommodation in
      pigmentary glaucoma and relationship to age.
AB  - PURPOSE: To examine the effect of accommodation on iris profile in pigmentary
      glaucoma and its relationship to age. DESIGN: Interventional case series.
      METHODS: We measured change in iris profile with accommodation in 92 eyes of 92
      patients with pigmentary glaucoma. RESULTS: Mean age was 42 years. Mean change in
      posterior iris excursion from nonaccommodated to accommodated state was 144.5
      microm. (P < .001). Age was plotted against iris excursion with an estimated
      least-squares regression line. The estimated Pearson correlation coefficient was 
      0.60, (P < .001). Patients younger than 42 years of age had a mean change in
      excursion of 209.2 microm compared with 79.8 microm for those patients older than
      42 years. (P < .001) CONCLUSION: This study found that there is a significant
      increase in posterior iris bowing in the accommodated state. Increasing age is
      associated with decreased posterior iris deviation. These findings add evidence
      to the theory of accommodation-induced reverse pupillary block in pigmentary
      glaucoma.

PMID- 15488799
TI  - Lidocaine tape (Penles) reduces the pain of botulinum toxin injection for Meige
      syndrome.
AB  - PURPOSE: To evaluate the efficacy of lidocaine tape in reducing pain during
      botulinum toxin injection. DESIGN: Randomized double-blind study. METHOD: Six men
      and four women with a diagnosis of Meige syndrome undergoing botulinum toxin
      injection were recruited. Lidocaine tape was applied to the eyelid skin of a
      randomly selected eye and placebo tape to the other eye. Pain during botulinum
      toxin injection was evaluated subjectively by a visual analogue scale. Side
      effects were also monitored. RESULTS: Mean subjective pain both on puncturing
      skin and on injection in the lidocaine group was significantly lower than that in
      the placebo group. Nine of 10 patients found lidocaine tape to be more effective
      than placebo tape in reducing pain during injection. CONCLUSIONS: Lidocaine tape
      is a simple and convenient method of reducing pain during botulinum toxin
      injection. This method is recommended for patients reluctant to receive this
      treatment because of pain during injection.

PMID- 15488800
TI  - Internal limiting membrane peeling using triamcinolone acetonide: histopathologic
      confirmation.
AB  - PURPOSE: To report histopathologic confirmation of the internal limiting membrane
      (ILM) using triamcinolone acetonide (TA). DESIGN: Interventional case report.
      METHODS: One eye of one patient who underwent macular hole repair using TA
      suspension to help visualize the internal limiting membrane (ILM). The specimen
      was sent to pathology. RESULTS: Triamcinolone acetonide greatly improved the
      visualization of the ILM; the peeled area was seen as an area lacking white
      specks. The macular hole closed with an improvement in vision. No adverse effects
      were observed during the follow-up period. The specimen was identified as ILM by
      histopathologic examination. CONCLUSION: Peeling of the ILM is facilitated by the
      use of TA. Microscopic confirmation of ILM was made.

PMID- 15488801
TI  - Macular hemorrhage after laser in situ keratomileusis (LASIK) with femtosecond
      laser flap creation.
AB  - PURPOSE: To report the first case of macular hemorrhage following laser in situ
      keratomileusis (LASIK) with femtosecond laser flap creation. DESIGN:
      Observational case report. METHODS: A 36-year-old woman underwent uncomplicated,
      bilateral, simultaneous LASIK procedures for correction of moderate myopia (-5.00
      diopters OD and -6.00 diopters OS). LASIK flap creation was performed using the
      IntraLase femtosecond laser. RESULTS: On postoperative day 1, the patient's
      uncorrected and best-corrected visual acuities were 20/20 OD and 20/40 OS. A
      dilated fundoscopic examination revealed a one-third disk diameter macular
      hemorrhage OS. An intravenous fluorescein angoiogram ruled out the presence of
      predisposing macular pathology. Two months after LASIK, the macular hemorrhage
      had cleared, and 6 months later, the BCVA improved to 20/25 OS. CONCLUSIONS:
      Macular hemorrhage may occur after LASIK, even in the absence of previously
      identified risk factors, such as high myopia, pre-existing choroidal
      neovasculaization, lacquer cracks, and sudden changes in intraocular pressure
      associated with microkeratome-assisted flap creation.

PMID- 15488802
TI  - Visual recovery after radiation therapy for bilateral subfoveal acute myelogenous
      leukemia (AML).
AB  - PURPOSE: Present a case of bilateral foveal acute myelogenous leukemic tumors
      that responded to radiation therapy. DESIGN: Case report. METHODS: A patient was
      diagnosed with bilateral subfoveal infiltration of known systemic acute
      myelogenous leukemia. He received a standard induction chemotherapy, followed by
      consolidation therapy for his systemic leukemia. However, despite a complete
      marrow response, the intraocular tumors did not regress. Therefore, he was given
      low dose (1950-cGy) ocular external beam radiation therapy. RESULTS: One course
      of systemic cytarabine chemotherapy failed to control the subfoveal tumors,
      leaving the patient at risk for permanent vision loss. In contrast, external beam
      radiation therapy improved his vision from 20/60 in his right eye to 20/20 and
      from 20/70 in his left eye to 20/25. CONCLUSION: Although systemic chemotherapy
      can be used to treat intraocular metastasis, external beam radiation may provide
      more prompt resolution of vision-threatening tumors.

PMID- 15488803
TI  - Endophthalmitis caused by Klebsiella species.
AB  - PURPOSE: To investigate clinical settings, antibiotic sensitivities, and visual
      outcomes associated with endophthalmitis caused by Klebsiella species. DESIGN:
      Retrospective case series. METHODS: Record review of patients with
      endophthalmitis caused by Klebsiella (1984 through 2003). RESULTS: Clinical
      settings included cataract surgery (one eye), trauma (two), perforated corneal
      ulcer (one), and endogenous associated with hepatic abscess (one). Pretreatment
      vision was hand motions or better in four eyes (80%). Initial treatment was
      enucleation (one eye), pars plana vitrectomy (two), and vitreous tap and
      injection (two); intravitreal antibiotics were administered to all nonenucleated
      eyes. Klebsiella was sensitive to one or more antibiotics administered initially
      in all cases. In nonenucleated eyes, final acuity was >or=20/400 in two, 1/200 in
      one, and light perception in one. CONCLUSION: Despite treatment with appropriate
      antibiotics, endophthalmitis caused by Klebsiella species is associated with
      generally poor visual outcomes.

PMID- 15488804
TI  - Microbiologic spectrum and susceptibility of isolates in scleral buckle infection
      in India.
AB  - PURPOSE: To present the microbial spectrum and susceptibility of isolates in
      scleral buckle infections in India. DESIGN: Retrospective case series. METHOD:
      Seventy-three isolates from 55 eyes with scleral buckle infection were studied.
      RESULTS: The isolates included 30 gram-positive cocci (41.1%), 15 acid-fast
      bacilli (20.5%), 11 fungi (15.1%), 10 gram-positive bacilli (13.7%), and 7 gram
      negative bacilli (9.6%). Eighteen eyes (32.7%) had polymicrobial infections. Gram
      positive, gram-negative, and acid-fast isolates were most commonly susceptible to
      vancomycin (93%), ciprofloxacin (86%), and amikacin (80%), respectively.
      CONCLUSION: This large single-center study indicates the high prevalence of
      fungal, acid-fast organisms and polymicrobial organisms in buckle infections.

PMID- 15488805
TI  - Association of the M55L and Q192R paraoxonase gene polymorphisms with age-related
      macular degeneration.
AB  - PURPOSE: To investigate the reported association of the two single-nucleotide
      polymorphisms (SNPs) of the paraoxonase gene (PON1), Met-Leu 55 (M55L) and Gln
      Arg 192 (Q192R), in individuals of Anglo-Celtic descent who have age-related
      macular degeneration (AMD). DESIGN: Case-control association study. METHODS:
      Sixty-two individuals with late (end-stage) AMD and 115 control subjects (without
      AMD) were included in this study. The M55L and Q192R SNPs were amplified by
      polymerase chain reaction and genotyped, and statistical analysis was undertaken.
      RESULTS: No association of either SNP was detected in persons of Anglo-Celtic
      descent who had AMD, although there was a significant difference in SNP allele
      frequency between Anglo-Celtic and Japanese individuals. CONCLUSION: The M55L and
      Q192R SNPs of the PON1 gene do not appear to be associated with late AMD in
      individuals of Anglo-Celtic descent.

PMID- 15488806
TI  - Intravitreal injections of triamcinolone acetonide for severe vitritis in
      patients with incomplete Behcet's disease.
AB  - PURPOSE: To report our experience with intravitreal triamcinolone acetonide
      (IVTA) injections for the treatment of sight-threatening vitritis. DESIGN:
      Interventional case series. METHODS: Three patients with acute severe
      exacerbations of noninfectious panuveitis and vitritis were treated with IVTA
      injections alone or as an adjunct to systemic immunosuppressive agents. RESULTS:
      Rapid clearance of the vitreous inflammation with improvement in visual acuity
      was observed 1 to 2 weeks after injection. The effect lasted 2 to 6 months, with
      the shortest duration in the vitrectomized eye of Patient 1. Repeated injections
      were required in all patients. CONCLUSION: Intravitreal triamcinolone acetonide
      may be beneficial in selected cases of vitritis. This treatment modality has a
      rapid effect and may lower the use of systemic agents.

PMID- 15488807
TI  - The comparability of estimates of retroilluminated lens opacities as judged from
      film-based and digital imaging.
AB  - PURPOSE: Neitz film-based retroillumination cameras, the standard for documenting
      retroilluminated lens opacities for epidemiologic studies, are no longer
      produced. A digital imaging system is now available for imaging these opacities.
      We sought to compare gradings of images from both systems. DESIGN: Comparison of
      technique. METHODS: One hundred fourteen lenses were imaged with both systems and
      graded according to protocols. Concordance between the methods was compared using
      kappa statistics. RESULTS: There was moderate concordance for cortical opacities
      (kappa = 0.63) and good concordance for posterior subcapsular opacities (kappa =
      0.83). Grades from digital images slightly underestimated the frequency and
      severity of cortical cataract. CONCLUSION: Digital imaging of retroilluminated
      lens opacities results in similar classification of the severity of opacities. It
      will be useful for epidemiologic studies of cortical (CC) and posterior
      subcapsular cataracts (PSC).

PMID- 15488809
TI  - Systemic remission of non-Hodgkin's lymphoma after intralesional interferon alpha
      2b to bilateral conjunctival lymphomas.
AB  - PURPOSE: To report the beneficial systemic effect of a 5-week course of
      intralesional interferon alpha-2b (IFN-A) injections to bilateral conjunctival
      lymphomas in a patient with relapsing non-Hodgkin's lymphoma. DESIGN:
      Interventional case report. METHODS: A patient in relapse with non-Hodgkin's
      lymphoma who declined further systemic therapy received 1.5-million IU IFN-A
      injected intralesionally to each of two conjunctival lymphomas to reduce ocular
      discomfort. This dose was repeated 10 times over 5 weeks. RESULTS: Conjunctival,
      postauricular, and facial lesions clinically resolved within 3 months of the
      start of treatment. Inguinal lymph nodes reduced in size, and the patient
      reported increased well-being and less fatigue. Side effects included injection
      discomfort and mild flulike symptoms, which were well tolerated. The improvement
      lasted 6 months from the first IFN-A injection. CONCLUSIONS: Intralesional
      treatment of conjunctival lymphomas with IFN-A induced disappearance of the
      tumors and also had a beneficial systemic effect.

PMID- 15488808
TI  - Novel mutation in FZD4 gene in a Japanese pedigree with familial exudative
      vitreoretinopathy.
AB  - PURPOSE: To identify the genetic defect in the FZD4 gene responsible for familial
      exudative vitreoretinopathy (FEVR) in a Japanese family. DESIGN: Interventional
      case report. METHODS: Complete ophthalmologic examinations were performed, and
      the FZD4 gene was analyzed by direct genomic sequencing. RESULTS: Fundus
      examination of a 13-year-old Japanese girl who had had esotropia and exudative
      retinal detachment at 3 years exhibited peripheral avascular areas bilaterally, a
      dragged disk, and retinal holes unilaterally. In contrast, her asymptomatic
      father had only bilateral avascular areas in the peripheral retina. Molecular
      genetic analysis revealed that both the proband and her father had a heterozygous
      missense mutation of A to G at 1026 bp of the FZD4 gene (Met342Val). CONCLUSIONS:
      A novel mutation in the FZD4 gene was identified in Japanese patients with FEVR.
      Our observations support the hypothesis that the FZD4-associated FEVR might
      represent a milder form than that associated with other genetic origins.

PMID- 15488810
TI  - Successful use of topical cysteamine formulated from the oral preparation in a
      child with keratopathy secondary to cystinosis.
AB  - PURPOSE: To report the successful use of topical cysteamine formulated from the
      oral preparation in the treatment of severe photophobia from corneal crystal
      deposition in cystinosis. DESIGN: Interventional case report. METHODS:
      Retrospective chart review. RESULTS: An 8-year-old boy with nephropathic
      cystinosis was experiencing debilitating and worsening photophobia from corneal
      crystal deposition. Because no parenteral cysteamine was available nationally,
      the oral capsule was used to formulate an ophthalmic preparation for
      compassionate use. After 8 months of topical application, the patient has marked
      improvement of his corneal disease, both subjectively and objectively.
      CONCLUSIONS: In situations of need, there is a role for the formulation of
      ophthalmic cysteamine from its oral preparation.

PMID- 15488811
TI  - Surgical technique for repositioning subluxated previously scleral-fixated
      intraocular lenses.
AB  - PURPOSE: To describe a repositioning technique of a subluxated scleral-fixated
      rigid intraocular lens (IOL) with haptic holes in eyes with complete or anterior
      vitrectomy. DESIGN: Interventional case series. METHODS: Using a two-port pars
      plana vitrectomy, a 10-0 polypropylene suture with the free end fixated to a
      haptic hole cut from another artificial IOL is passed through a paracentesis,
      then through the hole of the haptic luxated in the vitreous cavity. It is then
      reanchored at the sclera, repositioning the IOL. RESULTS: In the two eyes, visual
      acuity was restored to pre-subluxation levels. During 6-month follow-up, anatomic
      and functional results were stable, and there were no complications. CONCLUSIONS:
      This technique enables repositioning of a subluxated, previously sutured rigid
      IOL without externalization of the lens or haptics and with good results.

PMID- 15488812
TI  - Effect of chronic systemic use of trimethoprim-sulfamethoxazole in the
      conjunctival bacterial flora of patients with HIV infection.
AB  - PURPOSE: To investigate the effect of orally administered trimethoprim
      sulfamethoxazole (TMP-SMZ) on the prevalence, species distribution, and
      resistance of the conjunctival bacterial flora in adults with human
      immunodeficiency virus (HIV) infection. DESIGN: Cross-sectional study, with
      clinical and experimental laboratory investigation. METHODS: Samples from the
      inferior conjunctival fornix were collected and submitted for culture to evaluate
      aerobic flora. RESULTS: Sixty samples were collected. Negative cultures were
      found in 17 (56.7%) eyes of the TMP-SMZ group and in 10 (33%) of the control
      group (P = .036). All Staphylococcus species isolates in the TMP-SMZ group were
      resistant to the drug, whereas 50% of the control group presented this finding (P
      = .025). In the study group, all bacteria were resistant to TMP-SMZ, compared
      with only 47% of the microorganisms in the control group. CONCLUSION: Orally
      administered TMP-SMZ in patients with HIV infection seems to exert a selection
      pressure in the microorganisms present on the conjunctiva.

PMID- 15488813
TI  - Vitrectomy as a treatment for elevated intraocular pressure following
      intravitreal injection of triamcinolone acetonide.
AB  - PURPOSE: To report control of intravitreal triamcinolone acetonide-induced
      elevated intraocular pressure (IOP) by vitrectomy-assisted corticosteroid
      removal. DESIGN: Interventional case series. METHODS: Of the 26 eyes that had
      intravitreal injection of triamcinolone acetonide for various causes, 11 eyes
      (42.5%) developed elevated IOP. In nine eyes IOP was controlled by antiglaucoma
      medication. Two eyes of two patients developed uncontrolled IOP despite maximal
      antiglaucoma medication. These eyes underwent vitrectomy and removal of
      triamcinolone acetonide. RESULTS: IOP returned to normal in 3 weeks and 1 week,
      respectively, after vitrectomy. CONCLUSIONS: Elevated IOP associated with
      intravitreal injection of triamcinolone acetonide that is not controlled by
      maximal antiglaucoma medication can be effectively treated by vitrectomy-assisted
      removal of triamcinolone acetonide.

PMID- 15488814
TI  - Subperiosteal hematoma of the orbit following an aneurysm coiling procedure.
AB  - PURPOSE: To report a case of subperiosteal hematoma formation following
      endovascular stenting and coiling of an arterial aneurysm. DESIGN: Observational
      case report. METHODS: A 51-year-old woman presented with complaints of sudden
      proptosis, ptosis, and severe orbital pain following endovascular stent placement
      and coiling procedure of an internal carotid artery aneurysm. The patient did not
      have a history of recent head trauma. RESULTS: Magnetic resonance imaging showed
      a superior subperiosteal hematoma of the left orbit with downward displacement of
      the left superior rectus muscle. No intervention was taken, and the patient was
      closely monitored. Her symptoms resolved after 4 weeks. Spontaneous subperiosteal
      hematoma in the absence of trauma is rare. CONCLUSIONS: This is the first
      reported case of subperiosteal hematoma formation following endovascular stenting
      and coiling of an arterial aneurysm, which may have been the manifestation of
      anticoagulation and changes in orbital hemodynamics during and after the
      procedure.

PMID- 15488815
TI  - Secondary acute angle-closure glaucoma associated with vitreous hemorrhage after
      ruptured retinal arterial macroaneurysm.
AB  - PURPOSE: To report acute angle-closure glaucoma in a patient with dense vitreous
      hemorrhage due to a ruptured retinal arterial macroaneurysm. DESIGN:
      Interventional case report. METHODS: A male patient presented with severe pain
      and decreased vision in his right eye, nausea, and vomiting. Visual acuity was
      hand motions, intraocular pressure was 64 mm Hg, and light reflex was not
      detected in the right eye. The patient underwent comprehensive ophthalmologic
      examination and appropriate medical and surgical management. RESULTS: Examination
      of the right eye revealed a shallow anterior chamber and closed angle; ultrasound
      confirmed the presence of vitreous hemorrhage. After intensive medical treatment
      and subsequent pars plana vitrectomy with laser treatment to the ruptured retinal
      macroaneurysm, pain in the right eye subsided, visual acuity improved to 20/25,
      and intraocular pressure decreased to 20 mm Hg. CONCLUSION: We are unaware of
      previous clinical reports of this finding and could find no reference to it in a
      computerized search utilizing MEDLINE. In our patient the pressure stabilized and
      the vision improved after medical and surgical management.

PMID- 15488816
TI  - Baseline risk factors for the development of primary open-angle glaucoma in the
      Ocular Hypertension Treatment Study.
AB  - PURPOSE: Higher baseline pattern standard deviation (PSD) and larger vertical cup
      to-disk ratio (VC/D) were factors in the predictive model for the development of
      primary open-angle glaucoma (POAG) in the Ocular Hypertension Treatment Study.
      Because early changes in PSD and VC/D may be indicative of early POAG damage, we
      repeated the prediction model excluding PSD and VC/D. DESIGN: Reanalysis of
      baseline factors for the development of POAG. METHODS: We compared the hazard
      ratios for baseline factors predictive of POAG in the multivariate Cox
      proportional hazards model that included PSD and VC/D and in the model that
      excluded them. RESULTS: Hazard ratios for baseline factors predictive of POAG in
      Ocular Hypertension Treatment Study were not substantially affected by the
      inclusion or exclusion of PSD and VC/D in the proportional hazards model.
      CONCLUSION: Whether PSD or VC/D was included in the Cox proportional hazards
      model, the same baseline factors were statistically significant and their hazard
      ratios were essentially similar.

PMID- 15488818
TI  - The white dot syndromes.

PMID- 15488820
TI  - The challenge of determining aqueous contamination rate in anterior segment
      intraocular surgeries.

PMID- 15488822
TI  - Statins and age-related macular degeneration.

PMID- 15488823
TI  - Favorable visual outcome associated with subretinal indocyanine green in macular
      hole surgery.

PMID- 15488824
TI  - Anatomic and visual outcomes after indocyanine green-assisted peeling of the
      retinal internal limiting membrane in idiopathic macular hole surgery.

PMID- 15488826
TI  - Anatomic and visual outcomes after indocyanine green-assisted peeling of the
      retinal internal limiting membrane in idiopathic macular hole surgery.

PMID- 15488828
TI  - Positive angle kappa: a sign of albinism in patients with congenital nystagmus.

PMID- 15488830
TI  - Laser photocoagulation of indocyanine green aniographically identified feeder
      vessels to idiopathic polypoidal choroidal vasculopathy.

PMID- 15488834
TI  - Optic neuritis treatment trial:10-year follow-up results.

PMID- 15488836
TI  - Limitation of Scheimpflug videophotography system in quantifying posterior
      capsule opacification after intraocular lens implantation.

PMID- 15488838
TI  - Statin and aspirin therapy are associated with decreased rates of choroidal
      neovascularization among patients with age-related macular degeneration.

PMID- 15488840
TI  - A prospective, pilot study of treatment of amblyopia in children 10 to <18 years
      old.

PMID- 15488842
TI  - Therapeutic approaches in the treatment of ligneous conjunctivitis, the most
      common clinical manifestation of a systemic disease, caused by severe type I
      plasminogen deficiency.

PMID- 15488843
TI  - Neuroimaging in child abuse: reducing the risk.

PMID- 15488844
TI  - Imaging for primary hyperparathyroidism--what beginners should know.
AB  - For patients with primary hyperparathyroidism surgical removal of the
      hyperfunctioning parathyroid gland is curative. With advances in minimally
      invasive surgery, accurate pre-operative localization of the hyperfunctioning
      parathyroid tissue is essential to aid successful surgical treatment. The onus of
      identifying this hyperfunctioning parathyroid tissue therefore falls on imaging
      techniques such as high-resolution ultrasound, radionuclide imaging, computed
      tomography and magnetic resonance imaging. This article is not an exhaustive
      review, and its main aim is to familiarize the general radiologist, trainee
      radiologists and clinicians with the basics of various imaging techniques and
      their roles in practical management of patients with primary hyperparathyroidism.

PMID- 15488845
TI  - Computed tomography in the imaging of colonic diverticulitis.
AB  - Colonic diverticulitis occurs when diverticula within the colon become infected
      or inflamed. It is becoming an increasingly common cause for hospital admission,
      particularly in western society, where it is linked to a low fibre diet. Symptoms
      of diverticulitis include abdominal pain, diarrhoea and pyrexia, however,
      symptoms are often non-specific and the clinical diagnosis may be difficult. In
      addition, elderly patients and those taking corticosteroids may have limited
      findings on physical examination, even in the presence of severe diverticulitis.
      A high index of suspicion is required in such patients in order to avoid a
      significant delay in arriving at the correct diagnosis. Imaging plays an
      important role in establishing an early and correct diagnosis. In the past,
      contrast enema studies were the principal imaging test used to make the
      diagnosis. However, such studies lack sensitivity and have limited success in
      identifying abscesses that may require drainage. Conversely computed tomography
      (CT) is both sensitive and specific in making a diagnosis of diverticulitis. In
      addition, it is the imaging technique of choice in depicting complications such
      as perforation, abscess formation and fistulae. CT-guided drainage of
      diverticular abscesses helps to reduce sepsis and to permit a one-stage, rather
      than two-stage, surgical operation. The purpose of this review article is to
      discuss the role of CT in the imaging of diverticulitis, describe the CT imaging
      features and complications of this disease, as well as review the impact and
      rationale of CT imaging and intervention in the overall management of patients
      with diverticulitis.

PMID- 15488846
TI  - Imaging of lumbosacral transitional vertebrae.
AB  - Lumbosacral transitional vertebrae (LSTV) are a common finding in the general
      population. Their clinical significance is controversial with no consensus as to
      their relationship to low back pain or disc prolapse. However, on magnetic
      resonance imaging (MRI) they may be difficult to positively identify on sagittal
      sequences and can lead to confusion with respect to numbering of lumbar discs and
      vertebrae, with the consequent risk of surgical intervention at an inappropriate
      level. The imaging findings of LSTV on plain radiography and MRI are reviewed and
      their clinical significance discussed.

PMID- 15488847
TI  - Painful sclerosis of the medial end of the clavicle.
AB  - Pain and swelling of the medial end of the clavicle may be associated with
      radiographic sclerosis. The commonest causes are osteoarthritis, infection and
      condensing osteitis of the clavicle. Distinguishing between these clinically and
      radiologically can be difficult but computed tomography (CT) and magnetic
      resonance imaging (MRI) are often useful for their differentiation. In this
      review, the typical imaging features of these conditions are presented with an
      emphasis on the CT and MRI appearances. These are correlated with clinical
      features, which together should enable a confident diagnosis to be made.

PMID- 15488848
TI  - Further doubt is cast on the significance of the high intensity zone.

PMID- 15488849
TI  - Longitudinal study of high intensity zones on MR of lumbar intervertebral discs.
AB  - AIM: To study the temporal evolution of high intensity zones (HIZ) on MRI in
      patients with degenerative disease of the lumbar spine, and to evaluate whether
      any correlation exist between such evolution and in patient's symptoms. MATERIALS
      AND METHODS: HIZs in the MRI of 56 patients were included in the study. Each
      Patient had an initial and a follow-up scan performed at various time intervals.
      Scans were assessed for any change in HIZs by two observers (D. M. and I. W. M.).
      Patients' symptoms were assessed for by visual analogue score (VAS), the Oswestry
      Questionnaire Score (OQS) and patients' subjective assessment of change in
      symptoms. Any MRI feature, apart from HIZs, which could independently explain a
      patient's change in symptoms, was considered to be a confounding factor. Data
      were analysed separately in the whole group as well as in the group without
      confounding factors. RESULTS: On follow-up MRI, HIZs were found to have resolved
      in 17 lumbar disc levels (26.6%), improved in 9 (14%), worsened in 12 (18.8%) and
      remained unchanged in 26 (40.6%) at lumbar disc levels. Chi-square testing did
      not demonstrate any correlation between HIZ changes and evolution of patients'
      subjective symptoms (p = 0.26 for the whole group; p = 0.07 for the group without
      confounding factors). Similar lack of meaningful relationship was noted between
      HIZ changes and the VAS and OQS scores. CONCLUSION: We conclude that HIZs either
      do not change or improve spontaneously in a large proportion of cases over a
      period of time. Furthermore, there is no statistical correlation between HIZ
      changes and change in a patient's symptoms.

PMID- 15488850
TI  - Assessment of vertebral scalloping in neurofibromatosis type 1 with plain
      radiography and MRI.
AB  - AIM: To evaluate vertebral scalloping in patients with neurofibromatosis type 1
      (NF-1) and spinal deformity using plain radiographs and magnetic resonance
      imaging (MRI), and to determine the possible aetiological association with
      neurofibromas, dural ectasia and lateral meningocoeles. MATERIAL AND METHODS:
      Nineteen patients with NF-1, who had full spine radiographs and whole-spine MRI,
      were retrospectively reviewed. Dystrophic features and their relationship to the
      curve were recorded from radiographs. A comparison was then made between the
      dystrophic features evident on radiographs and adjacent soft-tissue abnormalities
      identified on MRI. RESULTS: Dystrophic changes were documented in 16 patients on
      plain radiographs and in all patients on MRI. Rib pencilling was the most common
      finding on radiographs. In 80% of the cases with scoliosis, scalloping was seen
      on the concavity of the curvature. In all patients with kyphoscoliosis,
      scalloping was contiguous to the apex of kyphosis. Twenty-four areas of
      scalloping were identified on MRI. Scalloping usually developed in the concavity
      of the scoliotic curve or at levels unrelated to the curve. Scalloping was
      evident in combination with dural ectasia or neurofibroma in 15 cases. The
      presence of dural ectasia was confirmed in 75% of the cases of posterior
      scalloping and in 25% of those of lateral scalloping. The presence of
      neurofibromas was recognized in 25% of the cases of anterior or lateral
      scalloping. Dural ectasia was identified in two patients without associated
      scalloping. Lateral meningocoeles were not related to the development of
      scalloping. CONCLUSION: Whereas posterior scalloping was commonly associated with
      dural ectasia, anterior and lateral scalloping were commonly the result of
      primary mesodermal dysplasia.

PMID- 15488851
TI  - Inter-observer agreement in audit of quality of radiology requests and reports.
AB  - AIMS: To assess the quality of the imaging procedure requests and radiologists'
      reports using an auditing tool, and to assess the agreement between different
      observers of the quality parameters. MATERIALS AND METHODS: In an audit using a
      standardized scoring system, three observers reviewed request forms for 296
      consecutive radiological examinations, and two observers reviewed a random sample
      of 150 of the corresponding radiologists' reports. We present descriptive
      statistics from the audit and pairwise inter-observer agreement, using the
      proportion agreement and kappa statistics. RESULTS: The proportion of acceptable
      item scores (0 or +1) was above 70% for all items except the requesting
      physician's bleep or extension number, legibility of the physician's name, or
      details about previous investigations. For pairs of observers, the inter-observer
      agreement was generally high, however, the corresponding kappa values were
      consistently low with only 14 of 90 ratings >0.60 and 6 >0.80 on the
      requests/reports. For the quality of the clinical information, the
      appropriateness of the request, and the requested priority/timing of the
      investigation items, the mean percentage agreement ranged 67-76, and the
      corresponding kappa values ranged 0.08-0.24. CONCLUSION: The inter-observer
      reliability of scores on the different items showed a high degree of agreement,
      although the kappa values were low, which is a well-known paradox. Current
      routines for requesting radiology examinations appeared satisfactory, although
      several problem areas were identified.

PMID- 15488852
TI  - MRI features of posterior ankle impingement syndrome in ballet dancers: a review
      of 25 cases.
AB  - AIM: To describe the magnetic resonance imaging (MRI) features of posterior ankle
      impingement syndrome (PAIS) in classical ballet dancers. MATERIALS AND METHODS: A
      retrospective review was undertaken of 25 MRI examinations of the ankle performed
      on 23 ballet dancers over a 26-month period. Images were examined for the
      presence of osseous and soft-tissue anatomical variants at the posterior ankle
      and imaging signs of PAIS. All patients presented with symptoms and signs
      suggestive of PAIS including posterior ankle pain, swelling and stiffness during
      plantar flexion. RESULTS: Anatomical variants predisposing to PAIS including as
      os trigonum and tuberosity arising from the superior calcaneum were clearly
      depicted. The most common imaging feature of PAIS in our series was high T2
      signal posterior to the talocalcaneal joint indicating synovitis (n = 25).
      Thickening of the posterior capsule (n = 13) and tenosynovitis of flexor hallucis
      longus (n = 17) were also common. An os trigonum was an infrequent finding (n =
      7). Bone marrow oedema, commonly in the posterior talus (n = 10) or in a patchy
      distribution (n = 10) was often noted. CONCLUSION: MRI is a useful diagnostic
      tool in PAIS, and in the present series, clearly demonstrates the anatomical
      variants and range of osseous and soft-tissue abnormalities associated with this
      condition. Prospective studies are needed to understand the significance and
      importance of individual MRI findings in producing the symptoms of PAIS.

PMID- 15488853
TI  - Evaluation of the anterior and posterior ethmoidal canal by computed tomography.
AB  - AIM: To examine the anatomy, length and angulation of the anterior and posterior
      ethmoidal canals (AECs and PECs) using computed tomography (CT), and to determine
      the anatomical landmarks in which the canals are expected to be seen in
      transverse and coronal planes. MATERIALS AND METHODS: CT images of 150 patients
      were analysed. One, 2, and 3 mm thick sections were obtained separately in axial
      and coronal images. The frequency of visualization of the AECs and PECs, and if
      present, a third canal, was noted. The course and the angulation of the AEC and
      the PEC in transverse and coronal planes were recorded. On axial sections the
      distance between the AEC and PEC and the previously defined landmarks were
      measured. On coronal images, the distances were calculated from the thickness of
      the cross-section and the number of sections between the various structures.
      RESULTS: The AEC was identified as a separate canal in 84% of patients, and was
      embedded in the ethmoid roof in 16%. The PEC was seen as a separate canal in 8%
      and was present in the ethmoid roof in 92%. On the 1 mm thick coronal and
      transverse sections, a third canal was identified at the junction of the middle
      and posterior third of the AEC-PEC distance in both of the images. The average
      lengths of these canals were 4-12 mm (mean 8.2 mm) for the AEC, and 2-13 mm (mean
      7.6 mm) for the PEC. CONCLUSIONS: To avoid the complications that can develop
      during endoscopic sinus surgery; the course, length and the angulations of the
      anterior and posterior ethmoidal arteries and their canals can be identified by
      CT in standard positions if a sufficiently thin section thickness is used. The
      present study has shown the exact CT localization of the AECs and PECS, which are
      frequently overlooked when evaluating para-nasal sinuses.

PMID- 15488854
TI  - Ureteric catheterization via an ileal conduit: technique and retrieval of a JJ
      stent.
AB  - Retrograde ureteric catheterization of a patient with an ileal conduit is
      difficult, because guide wires and catheters coil in the conduit. A modified
      loopogram, using a Foley catheter as a fulcrum through which catheters can be
      advanced to the ureteric anastomosis, is described. This technique was used to
      remove a JJ stent, which had been inserted previously across a stricture in one
      ureter, the stent crossing from one kidney to the other.

PMID- 15488855
TI  - Aortobronchopulmonary fistula after repair of aortic coarctation.

PMID- 15488856
TI  - Unilateral hyperlucent lung: MacLeod versus Swyer-James.

PMID- 15488858
TI  - Error and variation again.

PMID- 15488859
TI  - High levels of homocysteine inhibit lysyl oxidase (LOX) and downregulate LOX
      expression in vascular endothelial cells.
AB  - BACKGROUND: Hyperhomocysteinemia, an independent risk factor for cardiovascular
      disease and atherothrombosis, alters endothelial function through a mechanism not
      fully understood. Downregulation of lysyl oxidase (LOX), an enzyme involved in
      extracellular matrix maturation, impairs the endothelial barrier function and
      could be involved in homocysteine (HC)-induced endothelial dysfunction.
      OBJECTIVE: The aim of this study was to analyze the effect of HC on LOX
      regulation in vascular endothelial cells. RESULTS: HC at pathophysiological
      concentrations (35 microM) inhibited LOX activity in porcine aortic endothelial
      cells. Homocysteine thiolactone and related molecules containing sulfhydryl
      groups (cysteine), but not methionine or homocystine (non-containing thiol-group)
      inhibited LOX. In addition, the blockade of HC-sulfhydryl group by N
      ethylmaleimide abrogated HC-induced LOX downregulation. This process was
      triggered by oxidative stress since superoxide dismutase and vitamin C reverted
      LOX inhibition caused by HC. On the contrary, the effect was not mediated through
      the induction of endoplasmic reticulum stress. Finally, higher doses of HC (200
      microM), common in severe hyperhomocysteinemia, decreased LOX mRNA levels (
      approximately 2-fold) and LOX promoter activity in transient transfection
      experiments. CONCLUSIONS: These findings suggest that LOX inhibition contributes
      to the endothelial dysfunction associated with hyperhomocysteinemia. This effect
      was dependent on a mechanism involving both an inhibition of LOX activity and a
      reduction of LOX expression.

PMID- 15488860
TI  - Analysis of gender-specific atherosclerosis susceptibility in
      transgenic[hCETP]25DS rat model.
AB  - Epidemiological and clinical data demonstrate differences in atherosclerotic
      coronary heart disease prevalence between age-matched men and premenopausal
      women. Mechanisms underlying relative athero-susceptibility in men and athero
      resistance in premenopausal women remain to be elucidated. Lack of informative
      animal models hinders research. We report here a moderate-expresser line
      transgenic for human cholesteryl ester transfer protein (CETP) in the Dahl salt
      sensitive hypertensive rat strain, Tg25, that recapitulates premenopausal female
      athero-resistance. Having ascertained identical genetic background, environmental
      factors, and equivalent CETP hepatic RNA levels, we detect worse
      hypercholesterolemia, hypertriglyceridemia, coronary plaques and survival outcome
      in Tg25 male rats compared with Tg25 females. Hepatic transcription profiles of
      Tg25 males and females normalized to respective gender- and age-matched non
      transgenic controls exhibit significant differences. Genes implicated on
      hierarchical cluster analysis and quantitative real-time RT-PCR pinpoint pathways
      associated with coronary plaque progression such as inflammation and arachidonic
      acid epoxygenation, and not just cholesterol metabolism pathways. The data
      demonstrate gender-specific factors as key modulators of atherosclerosis
      phenotype and suggest a possible role for the liver in atheroma progression as a
      large organ source of proatherogenic systemic factors.

PMID- 15488861
TI  - Direct observation and quantitative analysis of spatiotemporal dynamics of
      individual living monocytes during transendothelial migration.
AB  - OBJECTIVE: To visualize and quantitatively analyze spatiotemporal dynamics of
      individual living monocytes during transendothelial migration (TEM). METHODS AND
      RESULTS: We developed an in vitro new experimental system using confocal laser
      scanning microscope with following two improvements: (1) ultra thin collagen gel
      layer (30-50 microm thick) constructed under human umbilical vein endothelial
      cell layer for three-dimensional observation with high magnification; (2)
      appropriate fluorescent labeling of living monocytes and endothelial cells to
      keep highest cell activity. Individual monocytes behaved quite diversely.
      Approximately 70% of adhered monocytes directionally crawled to intercellular
      junction, and started invasion. Time from adhesion to start of invasion was 8.6
      +/- 5.4 min (mean +/- S.D., n=61 monocytes). Approximately 80% of such invading
      monocytes completed TEM, but remaining 20% of once invading monocytes hesitated
      transmigration, and returned onto the endothelial surface. Time from start to
      finish of invasion was 6.3 +/- 3.2 min (mean +/- S.D., n=53 monocytes).
      CONCLUSIONS: Using our collagen gel-based newly-developed system, we visualized
      and quantitatively analyzed detailed spatiotemporal, three-dimensional dynamics
      of individual living monocytes during TEM. We revealed that monocytes encountered
      at least two hurdles, at starting invasion, and leaving endothelium, to achieve
      complete TEM. Approximately 56% (80% of 70% of adhered monocytes) passed both
      hurdles.

PMID- 15488862
TI  - Smooth muscle cell biglycan overexpression results in increased lipoprotein
      retention on extracellular matrix: implications for the retention of lipoproteins
      in atherosclerosis.
AB  - Lipoprotein retention on extracellular matrix (ECM) may play a central role in
      atherogenesis, and a specific extracellular matrix proteoglycan, biglycan, has
      been implicated in lipoprotein retention in human atherosclerosis. To test
      whether increased cellular biglycan expression results in increased retention of
      lipoproteins on ECM, rat aortic smooth muscle cells (SMCs) were transduced with a
      human biglycan cDNA-containing retroviral vector (LBSN) or with an empty
      retroviral vector (LXSN). To assess the importance of biglycan's
      glycosaminoglycan side chains in lipoprotein retention, ECM binding studies were
      also performed using RASMCs transduced with a retroviral vector encoding for a
      mutant, glycosaminoglycan-deficient biglycan (LBmutSN). Human biglycan mRNA and
      protein were confirmed in LBSN and LBmutSN RASMCs by Northern and Western blot
      analyses. HDL3+E binding to SMC ECM was increased significantly (as determined by
      95% confidence intervals for binding curves) for LBSN as compared to either LXSN
      or LBmutSN cells; the increases for LBSN cell ECM were due primarily to an
      approximately 50% increase in binding sites (increased Bmax) versus LXSN cell ECM
      and of approximately 25% versus LBmutSN cell ECM. These results are consistent
      with the hypothesis that biglycan, through its glycosaminoglycan side chains, may
      mediate lipoprotein retention on atherosclerotic plaque ECM.

PMID- 15488863
TI  - Artery interposed to vein did not develop atherosclerosis and underwent atrophic
      remodeling in cholesterol-fed rabbits.
AB  - Autologous vein grafts interposed to arteries are susceptible to the development
      of accelerated atherosclerosis. The effect of grafted artery interposed to vein
      on the atherosclerosis development and vascular remodeling is unknown. We
      investigated, therefore, the morphologic changes of artery grafts to vein in
      hyperlipidemic rabbits. Left common carotid artery grafts, approximately 5 cm
      long, were placed in the right external jugular vein position of 24 New Zealand
      White rabbits. After surgery, rabbits were fed with high lipid diet for 1, 2, 4
      and 12 weeks, respectively. Serum lipid levels were measured and the right common
      carotid artery and grafted left common carotid artery were harvested at above
      mentioned time points. Serum lipid levels were also measured in six rabbits
      receiving normal chow. Vessel wall thickness was measured and analyzed by image
      processing system. Hyperlipidemia occurred in all rabbits fed with high lipid
      diet. Fatty streak and atherosclerotic plaques were observed and lipid drops
      enriched in medial smooth muscle cells in control right common carotid arteries 4
      weeks after surgery. In the grafted arteries, no fatty streak and atherosclerotic
      plaque were seen and the vessel wall thickness decreased continuously after
      surgery (before surgery: 107.32 +/- 4.57 microm; 1 week: 94.50 +/- 5.78 microm*;
      2 weeks: 87.00 +/- 5.32 microm*; 4 weeks: 40.17 +/- 5.11 microm*;12 weeks: 18.00
      +/- 4.93 microm*, *p <0.05 versus before surgery). Three months after surgery,
      grafted arteries possess similar structures as that of veins. The artery
      interposed to vein did not develop atherosclerosis and underwent atrophic
      remodeling in cholesterol-fed rabbits suggesting that local hemodynamic load was
      the most important determinant influencing the development of atherosclerosis.

PMID- 15488864
TI  - IL-6 and the acute phase response in murine atherosclerosis.
AB  - Numerous studies have implicated C-reactive protein (CRP) and the acute phase
      response (APR) in the development of atherosclerotic heart disease. Interleukin
      (IL)-6, which regulates both CRP expression and the APR, has also been identified
      as a risk factor for heart disease. To more directly evaluate the role of IL-6 in
      the development of atherosclerosis, IL-6 knockout mice were crossed with
      atherosclerosis prone LDL receptor (LDL-R) knockout mice. Lesion development was
      evaluated on Chow, Western type and Paigen diets. As anticipated, the Paigen diet
      stimulated the expression of APR genes in LDL-R[-/-] mice, but not IL-6[-/-]/LDL
      R[-/-] mice. Despite this difference in acute phase response, only modest and
      statistically not significant differences were noted in the development of
      atherosclerotic lesions in LDL-R[-/-] and IL-6[-/-]/LDL-R[-/-] mice. These
      observations suggest that IL-6 and the acute phase response may not play as
      significant role in atherogenesis as other studies have indicated.

PMID- 15488865
TI  - Cytomegalovirus stimulated mRNA accumulation and cell surface expression of the
      oxidized LDL scavenger receptor, CD36.
AB  - OBJECTIVE: Cytomegalovirus (CMV) has been epidemiologically associated with
      multiple disease processes including coronary, carotid and cardiac graft
      atherosclerosis. An early initiating event in atherogenesis is the uptake by
      macrophages of oxidized low-density lipoproteins (OxLDL) via the scavenger
      receptor, CD36. Because CMV can activate host-cell gene transcription, we
      hypothesized that CMV may upregulate CD36 expression. METHODS AND RESULTS: THP-1
      monocyte/macrophage cells were treated with Davis strain CMV and cell surface
      CD36 expression measured by flow cytometry. Virus challenge increased the
      percentage of cells expressing CD36 from 21.8 +/- 1.7 to 48.2 +/- 4.0% (mean +/-
      S.D. for three experiments, P=0.0005); CD36 mRNA accumulation was increased by
      CMV treatment as determined by reverse transcription-polymerase chain reaction.
      Viral challenge also upregulated the mitogen-activated protein kinase p38;
      further, the specific p38 inhibitor, SB203580, reversed the CMV-induced CD36 cell
      surface expression from 57.2% of cells to baseline levels (29.0 and 30.1% for
      SB203580 treated and control cells, respectively; P=0.001). Treatment with virus
      also stimulated uptake of OxLDL: microscopically, virus-treated cells had a mean
      of 32 +/- 4.0 lipid vacuoles compared with 20 +/- 1.3 for control cells (P=0.01).
      CONCLUSIONS: These findings suggest that CMV-induced CD36 expression is one
      mechanism through which CMV may promote atherosclerosis. Other CMV-associated
      atherogenic mechanisms may exist; additional investigation is necessary.

PMID- 15488866
TI  - Peroxiredoxin 6 deficiency and atherosclerosis susceptibility in mice:
      significance of genetic background for assessing atherosclerosis.
AB  - Peroxiredoxin 6 (Prdx6; also called antioxidant protein 2, or Aop2) is a
      candidate gene for Ath1, a locus responsible for the respective susceptibility
      and resistance of mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) to diet-induced
      atherosclerosis. To evaluate if Prdx6 underlies Ath1, we compared the diet
      induced atherosclerotic lesions in Prdx6 targeted mutant (Prdx6-/-) mice of
      different genetic backgrounds: B6, 129, and B6;129. PRDX6 protein and mRNA were
      expressed in normal and atherosclerotic aortas. B6;129 Prdx6-/- macrophages
      oxidized LDL significantly more than did controls. Plasma lipid hydroperoxide
      levels were higher in atherogenic diet-fed Prdx6-/- mice with B6;129 and B6
      backgrounds than in controls. Prdx6-/- and controls in a 129 genetic background
      were equally lesion-resistant, and Prdx6-/- and controls in a B6 background were
      equally lesion-susceptible. In contrast, Prdx6-/- mice in a B6;129 background had
      significantly larger aortic root lesions than did littermate wild type controls.
      Therefore, although PRDX6 protein did not affect atherosclerosis susceptibility
      in either the resistant 129 background or the susceptible B6 background, it may
      inhibit atherosclerosis in backgrounds with mixed pro- and anti-atherogenic
      genes. Thus, genetic background plays an important role in modulating
      atherogenesis in targeted mutant mice. However, we think it is unlikely that
      Prdx6 underlies Ath1.

PMID- 15488867
TI  - Decrease of plasma triglycerides during the acute phase of unstable angina or non
      ST elevation myocardial infarction is a marker of recurrent ischemia.
AB  - Both increase and decrease of plasma triglycerides during acute coronary
      syndromes (ACS) are reported, however, a clinical relevance for these distinct
      metabolic responses is unclear. To test the association between distinct
      responses of lipid metabolism and cardiovascular risk, 39 subjects admitted with
      non-ST elevation ACS within 48 h of presentation had plasma lipids measured on
      the first and sixth days of hospitalization, and continuous electrocardiogram was
      performed during the first 2 days to quantify recurrent ischemia and heart rate
      variability. No lipid-lowering therapy was offered to the patients. During the
      first 5 days, half of them experimented a decrease in triglycerides (n=19,
      median: -18 mg/dl) and the other half presented triglyceride increase (n=20,
      median: +44 mg/dl). A higher incidence of recurrent ischemia (35% versus 5%,
      P=0.02) and greater ischemic burden/patient (123 +/- 286 mm min versus 47 +/- 212
      mm min, P=0.02) were observed in subjects with triglyceride reduction, when
      compared with those with triglyceride increase. Individuals with heart rate
      variability below the median presented a median decrease in triglycerides during
      the 5-day period, as opposed to the counterparts (P=0.05). In conclusion,
      triglyceride reduction during ACS is associated with a greater incidence of
      recurrent ischemia and may constitute a sign of higher sympathetic activity.

PMID- 15488868
TI  - Elevated soluble tumor necrosis factor receptor levels in non-obese adults with
      the atherogenic dyslipoproteinemia.
AB  - Adipose tissue expression of tumor necrosis factor-alpha (TNF-alpha) has been
      implicated in the pathogenesis of obesity-linked insulin resistance and the
      dyslipoproteinemia of insulin resistance. This study has two aims: (1) to compare
      select inflammatory mediators in non-smoking, normoglycemic male subjects with
      and without the atherogenic dyslipoproteinemia (ADL), and (2) to determine the
      effects of statin therapy on select inflammatory mediators. ADL subjects had
      higher levels of insulin (16.7 +/- 7.5 versus 11.6 +/- 5.9 microIU/mL, P=0.008),
      soluble TNF receptor superfamily 1B (sTNFRSF1B) (3.3 +/- 0.7 versus 2.7 +/- 0.5
      ng/mL, P=0.005), and interleukin-6 (IL-6) (2.6 +/- 2.2 versus 1.3 +/- 1.8 pg/mL,
      P=0.006) as compared to those of the non-ADL subjects. After adjustment for age,
      sTNFRSF1B (P=0.003) was more predictive of ADL than high-sensitivity C-reactive
      protein (hs-CRP) (P=0.047). Statin therapy did not change sTNFRSF1B, TNF-alpha,
      IL-6, hs-CRP, whereas soluble TNF receptor superfamily 1A (sTNFRSF1A) increased
      slightly (P=0.048). A high level of sTNFRSF1B is a strong marker of the pro
      inflammatory state in this sample of male ADL subjects.

PMID- 15488869
TI  - Prevalence of asymptomatic arteriosclerosis obliterans and its relationship with
      risk factors in inhabitants of rural communities in Japan: Tanno-Sobetsu study.
AB  - OBJECTIVES: Since arteriosclerosis obliterance in the legs (ASO) causes
      deterioration of the prognosis of the elderly, prevention of ASO is important for
      maintenance of their quality of lives. We studied the prevalences of ASO in rural
      communities in Japan. METHODS AND RESULTS: We measured the ratio of systolic
      blood pressure in the leg to that in the arm (ABI) using a new device, Form
      PWV/ABI, in 1398 subjects of both sexes. Subjects with ABI values below 0.9 were
      considered to have ASO. The prevalence of ASO was 2.7% in all of the subjects,
      1.0% in subjects under the age of 60 years, and 3.4% in subjects aged 65 years or
      more. Multiple regression analysis showed that ABI was correlated with plasma
      level of total cholesterol in men. There were no significant differences of the
      mean age, mean fasting plasma glucose level and percentage of patients who smoked
      between the ASO group and non-ASO group in each sex. Mean cholesterol level in
      our subjects is lower than the reported levels in Europeans and Americans. The
      prevalence of ASO increased with increase in the number of risk factors in
      individual subjects. CONCLUSIONS: Among the atherosclerotic risk factors, age and
      total cholesterol seem to be more important risk factors of ASO than others.

PMID- 15488870
TI  - Progesterone abolishes estrogen and/or atorvastatin endothelium dependent
      vasodilatory effects.
AB  - This double blind randomized placebo controlled study assessed the effects of
      atorvastatin, estradiol and norethisterone, isolated and in combination, on the
      lipid profile and on vascular reactivity, in post-menopausal women with
      hypercholesterolemia and arterial hypertension. Ninety-four women aged 50-65 were
      selected. All have received dietary counseling (4 weeks), placebo (4 weeks), and
      drug therapy (12 weeks): 17-beta estradiol 2mg/day (E) (n=17); E + norethisterone
      acetate 1mg/day (P) (n=18); Atorvastatin 10mg/day (A) (n=20); E + A (n=21) and E
      + P + A (n=18). All treatment modalities have significantly reduced total
      cholesterol (TC) (E=8.8%, E + P=10.1%, A=27.9%, A + E=29.4% and E + P + A=35.7%)
      and LDL-cholesterol (LDL-c) levels (E + P + A=46.6%, E + A=45.9%, A=40.2%,
      E=20.3%, and E + P=12.1%). As concerns HDL-cholesterol (HDL-c), Groups E and E +
      A had increases of 15.5% and 13.1%, respectively. The addition of a progesterone
      compound reduced its concentration (Group E + P=-9.1%, and Group E + P + A=
      9.5%). By random, approximately half of the patients in each group were
      designated to the endothelial function evaluation (brachial artery ultrasound).
      We observed that in Group A (n=10), in Group E (n=10) and with the association
      (Group E + A) (n=7), there was a significant increase in the flow-mediated
      vasodilatation as compared to basal measurements. The addition of a progestin has
      annulled these benefits. CONCLUSIONS: Atorvastatin has promoted more beneficial
      effects on TC and LDL-c, whereas estradiol was responsible for an increase in HDL
      c. The addition of a progesterone derivative abolished these benefits.
      Atorvastatin, estradiol or both together improved endothelial function, an effect
      suppressed by the addition of norethisterone.

PMID- 15488871
TI  - A combination of two common thrombomodulin gene variants (-1208-1209TTdelTT and
      A455V) influence risk of coronary heart disease: a prospective study in men.
AB  - In a previous case control study of myocardial infarction (MI), we identified
      risk associated with the combination of two variants in the thrombomodulin (TM)
      gene (-1208-1209TTdelTT and A455V) and an interaction with increased body mass
      index (BMI). The rare alleles at these two common variant sites in the TM gene
      occur in most individuals on the same allele (V/delTT) and are in strong linkage
      disequilibrium (Delta=0.67, P <0.0005). We have extended these findings in a
      prospective study of 2700 UK middle age men; the second Northwick Park Heart
      Study (NPHSII), in which 227 coronary heart disease (CHD) events have been
      reported to date. Risk was analysed by tertile of BMI, systolic blood pressure
      (SBP) and triglyceride. The strongest risk for the V/delTT haplotype was in the
      mid- and top-tertile of triglyceride; RR 1.95 (CI 1.12-3.40) and 1.77 (CI 1.02
      3.09), respectively, compared to non-carriers in the lowest tertile (after
      adjusting for age, practice, smoking, SBP, BMI; interaction P=0.016). No
      significant risk was identified for increased triglyceride levels in those with
      the common TM haplotype. There was a suggestion for greater inflammatory response
      (C-reactive protein levels, CRP) in those with V/delTT compared to those with the
      common allele, as triglyceride levels increased. Overall, these findings may
      suggest that the common TM allele confers protection against the adverse CHD
      effect of either plasma triglyceride-containing lipoproteins, or the underlying
      atherosclerotic mechanism of the metabolic syndrome, and that this process is
      defective in carriers of V/delTT.

PMID- 15488873
TI  - Effect of anti TNFalpha therapy on arterial diameter and wall shear stress and
      HDL cholesterol.
AB  - It has been recently hypothesized that both TNFalpha and anti TNFalpha treatment
      have a stimulating effect on nitric oxide synthesis and release. Moreover, an in
      vitro experiment has demonstrated that HDL-cholesterol binds TNFalpha. Aims of
      our study were to investigate wall shear stress of peripheral arteries and
      endothelial function of brachial artery in subjects with Rheumatoid Arthritis
      (RA) at baseline and after infliximab. Moreover, we evaluated the effect of anti
      TNFalpha therapy on lipid profile. Ten patients with RA received infliximab
      therapy at weeks 0, 2 and 6. Lipids and vascular parameters were measured before
      and the day after each infusion. After the first treatment, FMD increased (3.7 +/
      1.9% versus 17.5 +/- 2.9%, P <0.01) and common carotid and brachial artery
      diameters decreased (5.9 +/- 0.2 mm versus 5.5 +/- 0.2 mm; 3.5 +/- 0.4 mm versus
      3.1 +/- 0.4 mm, respectively, P <0.005). Common carotid and brachial artery wall
      shear stress increased (21.1 +/- 1.1 dynes/cm2 versus 23.9 +/- 1.4 dynes/cm2;
      42.0 +/- 4.7 dynes/cm2 versus 51.6 +/- 5.7 dynes/cm2, P <0.01). Similar results
      were observed after the second and third infusion. All these parameters returned
      to pre-treatment level at the following infusion. HDL-cholesterol and
      apolipoprotein AI significantly decreased after each treatment (1st treatment:
      1.4 +/- 0.05 mmol/L versus 1.2 +/- 0.06 mmol/L, P <0.01; 1.73 +/- 0.05 g/L versus
      1.57 +/- 0.02 g/L, P <0.03). The present data show vasoconstriction and an
      increase of wall shear stress in studied arteries after infliximab. HDL
      cholesterol is reduced by treatment and does not seem to influence FMD.

PMID- 15488872
TI  - No APOEepsilon4 effect on coronary heart disease risk in a cohort with low
      smoking prevalence: the Whitehall II study.
AB  - Carriers of the APOEepsilon4 allele have consistently shown higher, and epsilon2
      carriers have lower, plasma cholesterol and coronary heart disease (CHD) risk
      compared with epsilon3 homozygotes. An epsilon4:smoking interaction was observed
      in NPHSII, consistent with context dependency of the epsilon4 effect on CHD risk.
      In this study, APOE genotype was determined in 3787 male British civil servants
      followed for fatal and non-fatal myocardial infarction for median of 5.8 years,
      with 159 validated CHD events. APOE genotype was associated with expected effects
      on lipid traits (all P <0.0001). We tested the hypothesis that APOEepsilon4 was
      not a risk factor for CHD among non-smokers. In non-smokers, the odds ratio (OR)
      for epsilon2 and epsilon4 carriers were 0.51 (0.27, 0.97) and 0.70 (0.46, 1.08),
      respectively, compared with epsilon3 homozygotes. Thus epsilon2 carriers showed
      expected risk-protection, but despite 80% power to detect an OR in epsilon4
      subjects of 1.71 (i.e. of magnitude increase reported in prospective studies),
      the epsilon4 non-smokers showed no increased risk compared with epsilon3
      homozygotes. Smoking prevalence in this study was low (12.8%), but smokers had
      higher CHD risk which was of similar magnitude in risk in all genotypes [(OR 1.57
      (1.03, 2.40)]. These data, therefore, provide strong corroborative evidence that
      there is no elevated risk of CHD in epsilon4 non-smokers, but failed to confirm
      the epsilon4:smoking interaction on risk. This supports the context dependency of
      the epsilon4 risk effect, but the low smoking incidence in the Whitehall men
      reduced our ability to examine a smoking:genotype interaction.

PMID- 15488874
TI  - A prospective study of the APOA1 XmnI and APOC3 SstI polymorphisms in the
      APOA1/C3/A4 gene cluster and risk of incident myocardial infarction in men.
AB  - BACKGROUND: Apolipoproteins AI/CIII/AIV play important roles in the metabolism of
      triglycerides (TG) and high-density lipoprotein (HDL) cholesterol. However,
      whether genetic variations in the APOA1/C3/A4 gene cluster are associated with
      the risk of myocardial infarction (MI) remains uncertain and prospective data are
      sparse. METHODS: In a prospective nested case-control study of 385 incident cases
      of MI and 373 age- and smoking-matched controls from the Physicians' Health
      Study, we examined the relationship between 2 common single nucleotide
      polymorphisms (APOA1 XmnI and APOC3 SstI) in the APOA1/C3/A4 gene cluster and
      haplotypes defined by these SNPs and risk of incident MI. RESULTS: No significant
      differences in allele or genotype frequency for the APOA1 XmnI and APOC3 SstI
      polymorphisms were detected between cases and controls. After adjusting for non
      lipid coronary risk factors, the relative risks for incident MI were 1.00 (95% CI
      0.68-1.47) for men carrying the X2 allele compared with those homozygous for the
      X1 allele in the APOA1 XmnI site and 1.07 (95% CI 0.69-1.64) for men carrying the
      S2 versus those homozygous for the S1 allele in the APOC3 SstI site. Moreover, we
      did not observe any effect modification by HDL or TG levels for the associations
      of these APOA1 and APOC3 genotypes with MI risk. There were significant
      differences in TG levels among men carrying different haplotypes (P=0.01) and men
      carrying the X1-S2 haplotype had higher levels of TG than those carrying the X2
      S1 haplotype (202 mg/dl versus 157 mg/dl, P=0.03); however, haplotype frequencies
      defined by these two polymorphisms did not differ significantly between cases and
      controls. CONCLUSION: In this prospective study of apparently healthy middle-aged
      US men, carriers of the X1-S2 haplotype in the APOA1 XmnI and APOC3 SstI variants
      across the APOA1/C3/A4 gene cluster had higher TG levels, but there was no
      evidence for significant associations between these two common variants or
      haplotypes defined by them and risk of incident MI in this cohort.

PMID- 15488875
TI  - R643G polymorphism in PECAM-1 influences transendothelial migration of monocytes
      and is associated with progression of CHD and CHD events.
AB  - The 643R allele of R643G polymorphism (also known as R670G in the premature
      protein) in PECAM-1 has been associated with risk of myocardial infarction (MI),
      while the 643G allele has been associated with risk of coronary artery stenosis
      (CAS). The aim of this study was to investigate this apparently conflicting
      association. The association of R643G with risk of MI was determined in the
      second Northwick Park Heart study (2037 men with 138 CHD events; mean age: 56
      years). Smokers homozygous for the 643R allele showed increased risk of MI with a
      hazard ratio of 2.47 (95% CI: 1.23-4.97; P=0.01) compared to smokers homozygous
      for the 643G allele. Progression of disease was determined in the Lopid Coronary
      Angiography Trial (279 men; mean age: 58.9 years). The 643G homozygotes showed
      greater focal (-0.08 +/- 0.02 mm) and diffuse (-0.01 +/- 0.01 mm) progression of
      CAS compared to 643R homozygotes (-0.02 +/- 0.02 mm and 0.001 +/- 0.01 mm,
      respectively; P=0.04). While there was no genotype effect on platelet
      aggregation, PECAM-1 tyrosine phosphorylation in HUVECs of GG genotype was 2.4
      fold greater (P <0.01) than cells of RR genotype, and the level of
      transendothelial migration of monocytes of GG genotype was greater than that of
      monocytes of RR genotype following stimulation with either IL-1beta (12% higher,
      P <0.01) or TNF-alpha (10% higher, P=0.05). These data confirm the association of
      the R643G polymorphism with MI and CAS and suggest that greater influx of
      monocytes in individuals homozygous for the 643G may explain the association with
      CAS.

PMID- 15488876
TI  - Increased apoC-III production is a characteristic feature of patients with
      hypertriglyceridemia.
AB  - Apolipoprotein (apo) C-III plays an important role in regulating plasma
      triglyceride (TG) metabolism. In order to further investigate the plasma
      metabolism of apoC-III in hypertriglyceridemic subjects, we have studied the
      plasma kinetics of VLDL apoC-III, HDL apoC-III and total plasma apoC-III with a
      primed constant intravenous infusion of deuterated leucine in a group of male
      patients with mixed hyperlipidemia (type IIb hyperlipoproteinemia, HLP, n=6) and
      in a group with type III HLP (n=6). Compared to normolipidemic control subjects
      (n=5), patients with type IIb and type III HLP had significantly higher levels of
      plasma TG (0.89 +/- 0.15 mmol/l vs 2.56 +/- 0.40 mmol/l vs 8.76 +/- 1.39 mmol/l,
      respectively, P <0.01), plasma apoC-III (9.5 +/- 0.8 mg/dl vs 20.8 +/- 2.5 mg/dl
      vs 41.7 +/- 5.6 mg/dl, P <0.01) and VLDL apoC-III (3.6 +/- 0.8 mg/dl vs 14.6 +/-
      2.2 mg/dl vs 35.4 +/- 5.1 mg/dl, P <0.01). VLDL apoC-III production rates were
      significantly elevated in type IIb and type III patients (1.35 +/- 0.23 mg kg(-1)
      day(-1) vs 3.53 +/- 0.43 mg kg(-1) day(-1) vs 5.60 +/- 0.78 mg kg(-1) day(-1), P
      <0.01), as were total plasma apoC-III production rates (1.80 +/- 0.22 mg kg(-1)
      day(-1) vs 4.16 +/- 0.44 mg kg(-1) day(-1) vs 7.26 +/- 0.74 mg kg(-1) day(-1), P
      <0.01). VLDL apoC-III but not total plasma apoC-III fractional catabolic rates
      were reduced in type IIb and type III patients. Together with our previous
      results showing an increase of apoC-III production in patients with type IV HLP,
      and in overweight subjects with reduced insulin sensitivity, our data suggest
      that increased apoC-III production is a characteristic feature of patients with
      hypertriglyceridemia.

PMID- 15488877
TI  - Vascular effects of simvastatin combined with ramipril in hypercholesterolemic
      patients with coronary artery disease, compared with simvastatin alone: a
      randomized, double-blind, placebo-controlled, crossover study.
AB  - Because the mechanisms of the biological effects of statin and angiotensin
      converting enzyme inhibitor therapies differ, we studied the vascular responses
      to these therapies in hypercholesterolemic patients with coronary artery disease.
      We administered simvastatin 20 mg and placebo or ramipril 10 mg daily during 2
      months with washout 2 months to 32 hypercholesterolemic patients with coronary
      artery disease. This study was randomized, double-blind, placebo-controlled,
      crossover in design. Simvastatin alone or combined with ramipril significantly
      changed lipoproteins, and improved the percent flow-mediated dilator response to
      hyperemia relative to baseline measurements by 33 +/- 6% and by 50 +/- 14%,
      respectively (both P <0.001) and reduced plasma levels of nitrate relative to
      baseline measurements (P=0.413 and 0.037, respectively), the plasma MDA levels
      relative to baseline measurements by 8 +/- 8% and by 18 +/- 9% (P=0.039 and P
      <0.001, respectively) and MCP-1 relative to baseline measurements by 7 +/- 4% and
      by 13 +/- 3%, respectively (P=0.019 and P <0.001, respectively), and CRP from
      0.22 to 0.14 mg/dl and from 0.22 to 0.15 mg/dl, respectively (P=0.124 and 0.002,
      respectively), and PAI-1 antigen relative to baseline measurements (P=0.690 and
      0.018, respectively). However, simvastatin combined with ramipril changed to
      greater but statistically insignificant extent the percent flow-mediated dilator
      response to hyperemia and plasma levels of nitrate, MDA, MCP-1, and PAI-1 antigen
      than simvastatin alone. Simvastatin alone or combined with ramipril showed
      significant beneficial effects on endothelial function in hypercholesterolemic
      patients with coronary artery disease. However, simvastatin combined with
      ramipril did not significantly change, compared with simvastatin alone.

PMID- 15488879
TI  - Atorvastatin reduces proinflammatory markers in hypercholesterolemic patients.
AB  - BACKGROUND: Reduction in cardiovascular events with statins has been in part
      attributed to their anti-inflammatory properties. OBJECTIVE: Evaluate the effects
      of atorvastatin on levels of inflammatory markers, such as tumor necrosis factor
      alpha (TNF), interleukins (IL-1 and IL-6), soluble intercellular adhesion
      molecule-1 (sICAM-1) and C-reactive protein (CRP) in hypercholesterolemic
      patients (LDL-cholesterol >160 mg/dL). METHODS AND RESULTS: Two lipid-lowering
      regimens were taken for 8 weeks. One set of patients (n=45, 26 men, average 50 +/
      2 years of age) was subjected to atorvastatin treatment (20-40 mg/day), plus
      diet recommendation. Another set of patients (n=23, 12 men, average 53 +/- 3
      years of age) went through diet recommendation alone. Both groups were
      recommended to perform standard physical activity. Plasma samples were collected
      after overnight fasting at baseline and after 8 weeks for ELISA. The use of
      atorvastatin when compared to diet alone, resulted in significant (P <0.0001)
      reductions for: LDL-cholesterol (39.9% versus 4.4%), TNF (21.4% versus 2.9%), IL
      6 (22.1% versus 2.0%), IL-1 (16.4% versus 2.7%) and sICAM-1 (9.6% versus 0.1%),
      respectively. The percentage of patients with CRP levels >3 mg/dL in the
      atorvastatin group fell from 25.0 to 6.7% (P <0.0001) while in the diet group the
      reduction was not significant. CONCLUSION: In hypercholesterolemic patients,
      atorvastatin, compared to diet alone resulted in significant reductions in levels
      of proinflammatory cytokines (TNF, IL-1 and IL-6) as well as in sICAM-1 and CRP.
      Thus, statin-induced inhibition of inflammatory markers may play an important
      role in the pharmacological and clinical effects of statins seen in
      cardiovascular diseases.

PMID- 15488878
TI  - Angiotensin II type 1 receptor blockers reduce tissue factor activity and
      plasminogen activator inhibitor type-1 antigen in hypertensive patients: a
      randomized, double-blind, placebo-controlled study.
AB  - Angiotensin II stimulates the expression of tissue factor (TF) and plasminogen
      activator inhibitor type-1 (PAI-1), and AT1 receptor blockade (ARB) reduces PAI-1
      and TF activities in experimental studies. We investigated the effects of ARBs on
      TF activity, tissue plasminogen activator (tPA), PAI-1 antigen levels, plasma
      renin activity (PRA) and aldosterone levels in hypertensive patients. Placebo,
      losartan 100mg, irbesartan 300 mg, and candesartan 16 mg daily were administered
      to 122 patients for 2 months. Compared with placebo, ARBs significantly reduced
      TF activity (P <0.001 by ANOVA), and candesartan was the most potent. Compared
      with placebo or losartan, irbesartan and candesartan significantly lowered plasma
      levels of PAI-1 antigen (P <0.001 by ANOVA) with no differences between the two.
      Compared with placebo, all ARBs lowered plasma levels of aldosterone (P=0.012 by
      ANOVA) and increased PRA (P=0.005 by ANOVA). There were significant correlations
      between the degree of change in TF activity and PAI-1 antigen levels (r=0.458, P
      <0.0001) and between the change in TF activity and PRA (r=-0.296, P=0.006), but
      not with the magnitude of reduction in blood pressure following ARB therapy. ARBs
      significantly reduced TF activity, PAI-1 antigen levels, and aldosterone levels
      in hypertensive patients. The clinical significance of the varying potency of
      some ARBs needs to be further investigated.

PMID- 15488880
TI  - Q192R polymorphism of the paraoxanase 1 gene and its association with serum
      lipoprotein variables and carotid artery intima-media thickness in young adults
      from a biracial community. The Bogalusa Heart Study.
AB  - Paraoxanase (PON 1), a high-density lipoprotein-associated enzyme, exerts an
      antiatherogenic effect by protecting low-density lipoproteins (LDL) against
      oxidation. A common polymorphism at codon 192(Q/R) of the PON 1 gene has been
      shown to be associated with an adverse lipoprotein profile and increased coronary
      artery disease (CAD) risk. However, these observations are based mostly on case
      control studies involving relatively older adults. This study examined the
      frequency and phenotypic (lipoprotein variables) effect of the Q192R variant in a
      community-based sample of 1786 black and white young adults (mean age: 32.5
      years; 69% white, 44% males). In addition, the genotypic effect of this
      polymorphism on ultrasonographically measured carotid artery intima-media
      thickness (IMT), a surrogate measure of CAD risk, was examined in a subsample of
      436 young adults (mean age: 32.6 years; 70% white, 42% male). The frequency of
      the variant allele (R192) was higher in blacks than in whites (0.668 versus
      0.297, P <0.001). After adjusting for age, sex, body mass index, and smoking
      status, the R versus Q allele was associated with increased HDL cholesterol in
      whites (P=0.041), whereas the opposite was true in blacks (P=0.008). Neither the
      Q nor the R allele was associated with LDL cholesterol and triglycerides in both
      races. The genotypic effect on the carotid IMT adjusted for the covariates
      including lipoprotein variables was not apparent in whites or blacks. However,
      among whites, the carotid IMT was lower in carriers (QR + R) versus non-carriers
      (QQ) of the variant allele among females (P=0.008) and non-smokers (P=0.026). In
      addition, the variant allele negated the adverse positive relationship between
      the carotid IMT and triglycerides among whites (P=0.212 for carriers versus P
      <0.001 for non-carriers). These results indicate a differential effect of the
      Q192R variant on HDL cholesterol in whites versus blacks and a beneficial
      interaction effect of the variant allele with individual's sex, smoking status or
      triglyceride levels on the carotid IMT among whites.

PMID- 15488881
TI  - Activation of leukocytes by postprandial lipemia in healthy volunteers.
AB  - Activation of leukocytes is obligatory for inflammation and atherogenesis by
      adhering to the endothelium via specific ligands. Although in vitro studies have
      shown that triglycerides (TG) can activate leukocytes, it is unknown whether this
      occurs in vivo. Using flowcytometry, we studied the expression of leukocyte
      activation markers CD11A, CD11B, CD62L (all involved in endothelium adhesion) and
      CD66B (a neutrophil degranulation marker) during a 6 h fat challenge (50 g/m2)
      and a water test in 10 healthy males (52 +/- 3 years). After fat, neutrophil
      counts were increased between t=1 and t =6 h, with a maximum at t=3 h (+32%
      versus t=0, P <0.05), while they remained unchanged after water. Both tests
      showed gradual lymphocyte count increments. The expression of activation markers
      on lymphocytes was low and showed comparable responses after both tests. After
      fat, a significant increase up to a maximum at t=6 h was seen for CD11B on
      monocytes and on neutrophils for CD11B, CD62L and CD66B. Postprandial activation
      of monocytes and neutrophils was higher after fat than after water. The maximal
      postprandial TG increment was significantly related to the increase of CD11B on
      monocytes (Pearson's R=0.64, P <0.05). In conclusion, postprandially there is a
      TG-specific increase of neutrophil counts and increased activation of monocytes
      and neutrophils. These results are suggestive of a pro-inflammatory situation
      that may correspond with increased adhesive capacity of these cells contributing
      to the inflammatory component of atherosclerosis.

PMID- 15488882
TI  - Statin myotoxicity is associated with changes in the cardiopulmonary function.
AB  - The mechanism of the muscle toxicity associated with lipid-lowering therapy
      remains obscure. Pathological and biochemical findings in patients with statin
      myotoxicity suggest impaired fatty acid oxidation. Exhaled gas analysis can be
      used to assess substrate utilization including fatty acid oxidation. In order to
      determine if muscle toxicity due to lipid-lowering therapy might be related to
      abnormalities in lipid oxidation, exhaled gas analysis was performed in the
      fasted state on 11 patients subsequent to statin-associated myositis reactions.
      Results were compared to those of 16 normal controls who were measured both on
      and off statin therapy. Post-myositis patients showed a depressed anaerobic
      threshold (AT) (P=0.009) compared to controls while age-adjusted maximal oxygen
      consumption (VO2max) and ventilatory efficiency (VE/VCO2) were not significantly
      different. The fasting respiratory exchange ratio (RER) of post-myositis patients
      off statins was abnormally increased (P=0.00001) as was their S1-slope (P=0.023).
      Controls demonstrated a significant increase in their RER while taking statins
      consistent with decreased lipid oxidation (P <0.00001). These findings suggest
      that abnormal lipid oxidation in certain patients may predispose them to the
      myotoxicity caused by lipid-lowering therapies.

PMID- 15488883
TI  - Tissue factor promotor polymorphism -603 A/G is associated with myocardial
      infarction.
AB  - Tissue factor (TF), the main initiator of the extrinsic coagulation cascade is
      expressed in atherosclerotic lesions and contributes to coronary thrombus
      formation in myocardial infarction (MI). Circulating TF reflects intravascular TF
      activation but also adds to prothrombotic activation. Because the G allele of the
      TF promotor polymorphism -603 A/G is associated with monocytic mRNA expression we
      evaluated its association with myocardial infarction, based on a recessive
      deleterious effect assumption. Patients with MI (MI; n=793) and age and sex
      matched control subjects without coronary artery disease (C; n=340) undergoing
      coronary angiography were included. In patients with MI, the -603 G (MI: 76%, C:
      70%) allele was prevalent compared to the control group (P=-0.04). Multivariate
      analysis revealed an odds ratio of 1.44 (confidence interval 1.07-1.93). Carriage
      of the -603 G allele is associated with an increased risk for myocardial
      infarction. Because higher plasma TF concentrations are found in -603 G carriers
      enhanced TF expression may be the mechanism underlying this association.

PMID- 15488884
TI  - Reduced PAF-acetylhydrolase activity associated with Lp(a) in patients with
      coronary artery disease.
AB  - Lipoprotein(a) [Lp(a)] may be an independent risk factor for coronary artery
      disease (CAD). Lp(a) is enriched in platelet activating factor acetylhydrolase
      (PAF-AH), an enzyme which hydrolyzes and inactivates platelet activating factor
      (PAF) and oxidized phospholipids that are implicated in atherogenesis. We
      determined the mass and catalytic properties of the Lp(a)-associated PAF-AH in 28
      CAD patients in relation to the LDL-associated enzyme ones. Results were then
      compared to those of 30 control subjects and 16 unrelated patients with primary
      hypercholesterolemia (Type IIA dyslipidemia) before and after atorvastatin
      therapy. The mass, the specific activity and kinetic constants of the Lp(a)
      associated PAF-AH were significantly lower in CAD patients compared to those of
      either controls or hypercholesterolemic patients, a phenomenon not observed for
      LDL-associated PAF-AH. The enzyme specific activity and kinetic constants were
      significantly increased after removal of apo(a) from Lp(a) by reductive cleavage,
      which was not found in the control population, suggesting that the apo(a) moiety
      of Lp(a) from CAD patients may play an important role in the observed lower
      catalytic efficiency of PAF-AH. The reduced PAF-AH mass and specific activity on
      Lp(a) is a feature characteristic of this lipoprotein in CAD patients and may
      lead to a diminished capability of Lp(a) to degrade proinflammatory
      phospholipids. The consequences of this phenomenon as regards the
      pathophysiological role of Lp(a) in atherosclerosis remain to be established.

PMID- 15488885
TI  - Impaired high density lipoprotein antioxidant activity in healthy postmenopausal
      women.
AB  - The high incidence of atherosclerosis in women after menopause is associated with
      a risk pattern including an increase in low density lipoprotein (LDL), even
      though high density lipoprotein (HDL) cholesterol levels tend to be maintained or
      slightly decreased. Since estrogens are considered potent antioxidants, an
      increase in lipid peroxidation and formation of reactive oxygen species would be
      expected after menopause. If HDL becomes oxidized, the ability to protect LDL
      against oxidation may be impaired. In postmenopausal women there are scarce
      reports concerning HDL oxidability and no data about its antioxidant activity. We
      studied copper-induced oxidation and conjugated dienes formation in HDL isolated
      from 58 women, 30 postmenopausal (PMW) and 28 premenopausal (PreMW). None
      presented diabetes or cardiovascular disease and none was receiving hormonal,
      hypolipidemic or antioxidant therapy either. In order to evaluate the effect of
      HDL on LDL oxidation we isolated LDL and HDL from the same subject and assessed
      copper-induced LDL oxidation in the presence of HDL, followed by thiobarbituric
      acid-reactive substances determination. Relationships with HDL chemical
      composition, alpha-tocopherol content, cholesteryl ester transfer protein (CETP)
      and paraoxonase activity (PON) were investigated. HDL chemical composition in PMW
      exhibited triglyceride enrichment when compared to PreMW (p <0.05). alpha
      Tocopherol content and CETP activity were similar in both groups. However, CETP
      activity correlated positively with HDL triglyceride and negatively with HDL
      cholesterol percentage (r=0.44, p <0.01 and r=-0.32, p <0.05, respectively).
      Paraoxonase activity did not show differences between PMW and PreMW. When
      evaluating HDL oxidability, PMW revealed a shorter lag time in comparison to
      PreMW, even after adjustment for age, p <0.05. Moreover, when the effect of HDL
      on LDL oxidation was evaluated, HDL from PMW showed a reduction in its ability to
      inhibit LDL oxidation, compared to PreMW (p <0.05). In addition, the extent of
      inhibition of LDL oxidation by HDL was positively correlated with HDL resistance
      to oxidation (r=0.27, p <0.05). After women classification by paraoxonase
      phenotype, HDL ability to protect LDL against oxidation remained reduced only in
      PMW belonging to the PON QR phenotype, in comparison to PreMW QR. These results
      suggest that HDL from PMW exhibits impairment in its antioxidant ability, which
      is associated to a decreased HDL resistance to oxidation. In turn, this was
      related to triglyceride enrichment of HDL particles. All these alterations were
      independent from HDL cholesterol plasma levels.

PMID- 15488886
TI  - About the relationship between infection and atherosclerosis: the importance of
      adequate serological markers.

PMID- 15488888
TI  - Undertreatment of dyslipidaemia in Greece.

PMID- 15488889
TI  - Genetic polymorphisms affecting the phenotypic expression of patients with
      molecularly defined familial hypercholesterolaemia.

PMID- 15488890
TI  - Hyaluronic acid of high molecular weight inhibits proliferation and induces cell
      death in U937 macrophage cells.
AB  - Hyaluronic acid (HA), a major glycosaminoglycan component of the extracellular
      matrix, has regulatory influences on cells and cellular activities. To explore
      the effects of a high concentration (1 mg/mL) of high molecular weight HA (500
      730 kD) on U937 macrophage growth dynamics, three factors that influence overall
      cellular growth, namely proliferation, apoptosis, and cell death, were examined.
      Cells were cultured with HA and were analyzed by flow cytometry every 24 hours
      during a 168-hour period for proliferation and the presence of apoptotic and dead
      cells. These analyses demonstrated that HA inhibits U937 macrophage proliferation
      in a time-dependent manner. Through the first 72 hours, cells exhibited slowed
      proliferation. However, no evidence of cell division arrest or reduced cell
      viability was observed. Thereafter, HA continued to diminish proliferation, but
      induced apoptosis. This data is consistent with regulatory influences secondary
      to HA binding to CD44 and/or RHAMM cell surface receptors, both of which were
      shown to be expressed on U937 macrophages. This study demonstrates that a high
      concentration of high molecular weight HA greatly inhibits macrophage population
      growth by the dual actions of impeding cell proliferation and inducing apoptosis.

PMID- 15488891
TI  - Comparative analysis of the proteome of left ventricular heart of
      arteriosclerosis in rat.
AB  - Despite the worldwide occurrence of coronary atherosclerotic heart disease
      (CAHD), the pathogenic mechanisms underlying this disease remain largely unknown.
      In this study, the experimental model of atherosclerosis in rat (CAHD rat) was
      established by the injection of vitamin D3 associated with high fat diet for 6
      weeks. By using the proteomic approach, we comparatively analyzed the proteome of
      the control and CAHD rat left ventricular myocardial tissues. We reproducibly
      separated over 2500 polypeptides by using two-dimensional electrophoresis (2-DE)
      at pH range of 3-11. Among these proteins, 26 proteins with large amount were
      identified using micro high performance liquid chromatography mass
      spectrometer/mass spectrometer (micro-HPLC-MS/MS). Using PDQUEST software to
      process the 2-DE gel images, 38 protein spots that significantly altered in CAHD
      were detected. Of these, 12 proteins were identified with high confidence by
      using 2-DE and matrix-associated laser desorption ionization time-of-flight mass
      spectrometer (MALDI-TOF-MS). The identification of protein alterations specify to
      CAHD would clarify the pathogenetic mechanisms involved in the disease and might
      be of prognostic and therapeutic benefit.

PMID- 15488892
TI  - Effect of exercise on hepatic gene expression in rats: a microarray analysis.
AB  - Exercise has various beneficial effects on liver function, enhancing both
      nutrient metabolism and antioxidant capacity. To explore the molecular mechanisms
      underlying these changes, we used a high-density cDNA microarray containing probe
      sets for 2,845 genes to analyze changes of gene transcription in the livers of
      rats after 4 weeks of running exercise. In comparison with sedentary animals, 105
      genes were up-regulated and 86 genes were down-regulated, including genes with
      unknown functions. In addition, we detected an increase of p38 mitogen-activated
      protein kinase and protein and of the protein for signal transducer and activator
      of transcription 3 (stat3), corresponding to the increase of these mRNAs shown by
      microarray analysis. These results indicate that long-term exercise can alter
      liver function via changes of gene expression, especially the genes encoding
      signal transduction proteins such as p38 and stat3.

PMID- 15488893
TI  - Identification and synthesis of norhydromorphone, and determination of
      antinociceptive activities in the rat formalin test.
AB  - The main objective of this paper is to report the identification and synthesis of
      norhydromorphone, a novel metabolite of hydromorphone, and its antinociceptive
      activities when tested in the formalin test as compared to other known
      analgesics. In addition, we are reporting for the first time the lack of
      antinociceptive activities of hydromorphone-3-glucuronide, dihydromorphine-3
      glucuronide and dihydroisomorphine-3-glucuronide in the rat formalin test.
      Norhydromorphone was isolated and identified as a metabolite of hydromorphone in
      a cancer patient's urine. An authentic standard of norhydromorphone was
      synthesized. The identity of norhydromorphone in the urine sample was confirmed
      by comparing the LC retention time and MS ion fragmentation with the synthetic
      standard using a liquid chromatographic-mass spectrometric-mass spectrometric (LC
      MS-MS) assay. Norhydromorphone was found to be a minor metabolite of
      hydromorphone in the urine. Additionally, the antinociceptive activities of
      norhydromorphone, hydromorphone, morphine, dihydromorphine, dihydroisomorphine,
      hydromorphone-3-glucuronide, dihydromorphine-3-glucuronide and dihydroisomorphine
      3-glucuronide were determined in the rat formalin test following intraperitoneal
      (i.p.) administration. Only limited antinociception was observed and no
      significant increase in antinociception was detected at the three doses tested.
      The increased polarity of norhydromorphone as compared to hydromorphone due to
      the primary piperidine nitrogen may make it less favorable to cross the blood
      brain-barrier (BBB), which may be partly responsible. In addition, lower
      intrinsic antinociceptive activity, which remains to be determined, could also
      contribute to the low antinociception. Our results also show that hydromorphone
      was five times as potent as morphine in the formalin test, while dihydromorphine
      and dihydroisomorphine were equipotent to and 36% as potent as morphine,
      respectively. Hydromorphone-3-glucuronide, dihydromorphine-3-glucuronide and
      dihydroisomorphine-3-glucuronide did not exhibit any antinociceptive effect at
      the doses tested. The results further underscore the importance of a free C3-OH
      to the analgesic effect of morphine alkaloids.

PMID- 15488894
TI  - The actions of a charged melatonin receptor ligand, TMEPI, and an irreversible
      MT2 receptor agonist, BMNEP, on mouse hippocampal evoked potentials in vitro.
AB  - We have previously determined that melatonin modulates hippocampal synaptic
      transmission in a biphasic way: an initial depression was followed by a
      recovery/amplification phase. Here we describe the influence of two novel
      melatonin receptor ligands, BMNEP (N-bromoacetyl-2-iodo-5-methoxytryptamine) and
      TMPEI (N-[2-(2-Trimethylammoniumethyleneoxy-7-methoxy)ethyl]propionamide iodide),
      on the population spike (PS) and excitatory postsynaptic potentials (EPSP)
      recorded from mouse hippocampal slices. BMNEP, which specifically alkylates and
      constitutively activates the MT2 melatonin receptor, mimicked the first phase of
      melatonin's action by irreversibly depressing both the PS and EPSP. TMPEI, a
      charged ligand of plasma membrane melatonin receptors, amplified those potentials
      in a manner similar to the effect of melatonin observed during the second,
      recovery phase. Melatonin had no influence on the potentials amplified by the
      action of TMPEI. Our results suggest that the biphasic, receptor-dependent action
      of melatonin and its analogs modulates the efficiency of the hippocampal
      glutamergic synapse and is most likely mediated through two different,
      sequentially occurring mechanisms.

PMID- 15488895
TI  - Protective effects of Danshensu from the aqueous extract of Salvia miltiorrhiza
      (Danshen) against homocysteine-induced endothelial dysfunction.
AB  - Homocysteine (Hcy) is a by-product of methionine metabolism. An imbalance of Hcy
      in the body may lead to hyperhomocysteinemia, a condition with elevated Hcy
      concentration in blood that may be one of the risk factors responsible for the
      development of several vascular diseases (thromboembolism, atherosclerosis,
      stroke, vascular diseases and dementia). Radix Salvia miltiorrhiza (Danshen), a
      well-known Chinese medicinal herb that can activate and improve blood
      microcirculation, is noticeable for its beneficial effect in treating
      cardiovascular diseases. The present study is to demonstrate the protective
      effect of Danshen extract against the homocysteine-induced adverse effect on
      human umbilical vein endothelial cell (HUVEC). Homocysteine (5 mM) not only
      decreased the cell viability but also caused the disruption of capillary-like
      structure formation in vitro. The protective effect of Danshen aqueous extract
      and its active compounds on endothelial cell function were demonstrated through
      an in vitro tube formation assay, which mimics the new blood vessel formation. To
      identify the active components in the aqueous extract of Danshen, the content was
      characterized by instrumental analysis using high performance liquid
      chromatography with diode array detector (DAD) and electrospray tandem mass
      spectrometry (ESI-MS/MS). Interestingly, Danshen extract and its pure compounds
      showed different effectiveness in protecting HUVEC against Hcy-induced injury
      according to the following descending order: Danshen aqueous extract, 3-(3,4
      dihydroxy-phenyl)-2-hydroxy-propionic acid (Danshensu), protocatechuic acid,
      catechin and protocatechualdehyde. We believed that such findings might provide
      evidence in understanding the beneficial effects of Danshen on the cardiovascular
      system.

PMID- 15488896
TI  - Effect of IL-1alpha on the expression of cartilage matrix proteins in human
      chondrosarcoma cell line OUMS-27.
AB  - We examined the effect of the inflammatory mediator interleukin-1alpha (IL
      1alpha) on cell proliferation, alkaline phosphatase (ALPase) activity, and the
      expressions of cartilage matrix proteins, bone morphogenetic protein-2 (BMP-2),
      and BMP-2 receptors in human chondrosarcoma cell line OUMS-27 (chondrocytes). The
      cells were cultured with Dulbecco's modified Eagle's medium containing 15% fetal
      bovine serum with 0, 1, 10, or 100 units/ml of IL-1alpha for up to 14 days. The
      expressions of cartilage matrix proteins, BMP-2, and BMP-2 receptors were
      estimated by determining mRNA levels using semiquantitative or real-time PCR
      and/or by determining protein levels using Enzyme-linked immunosorbent assay.
      Cell proliferation was decreased after 5 days in culture with IL-1alpha. The
      ALPase activity was decreased significantly in the presence of IL-1alpha until
      day 10 of culture. The expression of type II collagen was significantly decreased
      after 7 days in culture with IL-1alpha. The expressions of aggrecan and link
      protein were significantly decreased through day 14 of culture with IL-1alpha.
      The expression of BMP-2 was increased at days 3, 7, and 14 of culture with IL
      1alpha, while the expression of type II receptor for BMP-2 was significantly
      decreased in the samples. These results suggest that IL-1alpha suppresses the
      expression of cartilage matrix proteins through a suppression of the autocrine
      action of BMP-2, brought about by the decrease in BMP-2 receptor expression in
      chondrocytes.

PMID- 15488897
TI  - The effect of high glucose on NO and O2- through endothelial GTPCH1 and NADPH
      oxidase.
AB  - Although endothelial dysfunction deteriorates diabetic angiopathy, the mechanisms
      are obscure. We revealed that high glucose augmented eNOS through stimulation of
      eNOS mRNA in cultured BAECs. NO was decreased and O2- was increased
      simultaneously. NOS inhibitor, inhibited O2- release, so did NADPH oxidase
      inhibitor. The effects were synergistic. Both intracellular BH4 level and GTPCH1
      activity were decreased by high glucose, in line with decrease of GTPCH1 mRNA.
      HMG-CoA reductase inhibitor, atorvastatin increased GTPCH1 mRNA and activity, and
      BH4 level. Conclusively, high glucose leads to eNOS dysfunction by inhibiting BH4
      synthesis and atorvastatin stimulate BH4 synthesis directly, and it may work as
      atherogenic process.

PMID- 15488898
TI  - Red yeast rice extracts suppress adipogenesis by down-regulating adipogenic
      transcription factors and gene expression in 3T3-L1 cells.
AB  - The effects of red yeast rice extracts (RE) on adipocyte differentiation of 3T3
      L1 cells were studied. RE were extracted from embryonic rice fermented with red
      yeast (Monascus ruber). These extracts significantly decreased glycerol-3
      phosphate dehydrogenase (GPDH) activity and lipid accumulation, a marker of
      adipogenesis, in a dose-dependent manner. Moreover, mRNA expression levels of
      both CCAAT/enhancer-binding protein (C/EBP) alpha and peroxisome proliferator
      activated receptor (PPAR) gamma, the key adipogenic transcription factors, were
      markedly decreased by RE. RE also inhibited the expression of PPARgamma at
      protein levels. RE decreased significantly gene expression of adipocyte fatty
      acid binding protein (aP2) and leptin, which are adipogenic marker proteins and
      C/EBPalpha and PPARgamma target genes. These results suggest that the inhibitory
      effect of RE on adipocyte differentiation might be mediated through the down
      regulated expression of adipogenic transcription factors and other specific
      genes.

PMID- 15488899
TI  - Perceptual deficits in amnesia: challenging the medial temporal lobe 'mnemonic'
      view.
AB  - Recent animal studies suggest that the medial temporal lobe (MTL), which is
      thought to subserve memory exclusively, may support non-mnemonic perceptual
      processes, with the hippocampus and perirhinal cortex contributing to spatial and
      object perception, respectively. There is, however, no support for this view in
      humans, with human MTL lesions causing prominent memory deficits in the context
      of apparently normal perception. We assessed visual discrimination in amnesic
      cases to reveal that while selective hippocampal damaged patients could
      discriminate faces, objects, abstract art and colour, they were significantly
      poorer in discriminating spatial scenes. By contrast, patients with MTL damage,
      including perirhinal cortex, were significantly impaired in discriminating
      scenes, faces, and to a lesser extent objects, with relatively intact
      discrimination of art and colour. These novel observations imply that the human
      MTL subserves both perceptual and mnemonic functions, with the hippocampus and
      perirhinal cortex playing distinct roles in spatial and object discrimination,
      respectively.

PMID- 15488900
TI  - Neural mechanisms involved in the detection of our first name: a combined ERPs
      and PET study.
AB  - In everyday social interactions, hearing our own first name captures our
      attention and gives rise to a sense of self-awareness, since it is one of the
      most socially self related stimulus. In the present study, we combined ERPs and
      PET scan methods to explore the cerebral mechanisms underlying the detection of
      our own name. While categorical analyses of PET data failed to reveal significant
      results, we found that the amplitude of the P3 component, elicited when hearing
      one's own name, correlates with regional cerebral blood changes in right superior
      temporal sulcus, precuneus and medial prefrontal cortex. Additionally, the latter
      was more correlated to the P3 obtained for the subject's name compared to that
      obtained for other first names. These results suggest that the medial prefrontal
      cortex plays the most prominent role in self-processing.

PMID- 15488901
TI  - Impaired generalization of weight-related information during grasping in
      cerebellar degeneration.
AB  - When we repetitively lift an object, the balance between grip force normal to the
      object's surface and load force tangential to the object's surface is accurately
      programmed to match the physical object properties within a few lifts. Here, we
      ask if the accuracy of grip force scaling to object weight and the transfer of
      weight-related information from one hand to the other is impaired in cerebellar
      degeneration. Subjects with generalized cerebellar degenerative disorders were
      tested. Subjects first repeatedly lifted a constant weight with the dominant
      hand, followed by a series of lifts of the same weight with the opposite hand.
      The experiments were performed with a light and a heavy weight. Patients and
      controls scaled the grip force output differentially to different weight. The
      comparison of grip force scaling for the first and last lifts with a constant
      weight demonstrated that healthy subjects and cerebellar patients adjusted grip
      forces more accurately to a specific weight with increasing number of lifts
      performed at each hand. The ability to transfer weight-related information from
      one hand to the other was analyzed by comparing the last lift with a constant
      weight of the dominant hand with the first lift of the same weight performed by
      the opposite hand. Healthy subjects scaled the grip force output precisely to a
      given weight immediately after a change in hand, suggesting that they succeeded
      to transfer weight-related information in between both hemispheres. In contrast,
      cerebellar patients produced an inaccurate grip force overshoot when lifting a
      given weight with the opposite hand. Our data suggest that the cerebellum plays a
      major role for the generalization of weight-related information during object
      manipulation.

PMID- 15488902
TI  - Action simulation for others is not constrained by one's own postures.
AB  - Does the brain use the same mechanism to simulate both our own and other persons'
      actions? If it does, then one's current posture should influence action
      simulation for others, depending on whether current and imagined postures differ.
      To test this prediction, 20 observers sat upright or bent forward while
      evaluating the reaching range of a model that had been photographed in similar
      postures. Posture congruency did not influence performance but decisions were
      faster and more accurate when the simulation required fewer posture changes.
      These results begin to reveal the processes that transform visual inputs into
      motor predictions for others. Implications of the present findings for our
      understanding of the so-called "mirror system" are discussed.

PMID- 15488903
TI  - Visual-field asymmetry in dual-stream RSVP.
AB  - The attentional blink (AB) refers to a decrement in detecting the occurrence of a
      probe item if it closely follows a previous target item in rapid serial visual
      presentation (RSVP). In the present study we presented target and probe stimuli
      in two parallel RSVP streams, one in each visual field, in order to address the
      question of whether the AB might differ between the cerebral hemispheres. The
      characteristic AB, with reduced detection of the probe at post-target Lags 2-5,
      but no such deficit at Lag 1 (Lag 1 sparing), was observed when target and probe
      were both in the right visual field. When they were both presented in the left
      visual field the AB was attenuated. When the target and probe were in opposite
      visual fields, probe detection was again reduced when it was in the left visual
      field, and there was no Lag 1 sparing. The left-visual-field advantage in
      performing the AB task may reflect a general right-hemispheric specialization for
      attentional processing.

PMID- 15488904
TI  - Segregation and persistence of form in the lateral occipital complex.
AB  - While the lateral occipital complex (LOC) has been shown to be implicated in
      object recognition, it is unclear whether this brain area is responsive to low
      level stimulus-driven features or high-level representational processes. We used
      scrambled shape-from-motion displays to disambiguate the presence of contours
      from figure-ground segregation and to measure the strength of the binding process
      for shapes without contours. We found persisting brain activation in the LOC for
      scrambled displays after the motion stopped indicating that this brain area
      subserves and maintains figure-ground segregation processes, a low-level function
      in the object processing hierarchy. In our second experiment, we found that the
      figure-ground segregation process has some form of spatial constancy indicating
      top-down influences. The persisting activation after the motion stops suggests an
      intermediate role in object recognition processes for this brain area and might
      provide further evidence for the idea that the lateral occipital complex
      subserves mnemonic functions mediating between iconic and short-term memory.

PMID- 15488905
TI  - Are the perceptual biases found in chimeric face processing reflected in eye
      movement patterns?
AB  - Studies of patients with focal brain lesions and neuroimaging indicate that face
      processing is predominantly based on right hemisphere function. Additionally,
      experiments using chimeric faces, where the left and the right-hand side of the
      face are different, have shown that observers tend to bias their responses toward
      the information on the left. Here, we monitored eye-movements during a gender
      identification task using blended face images for both whole and chimeric (half
      female, half male) faces [Neuropsychologia 35 (1997) 685]. As expected, we found
      a left perceptual bias: subjects based their gender decision significantly more
      frequently on the left side of the chimeric faces. Analysis of the first saccade
      showed a significantly greater number of left fixations independent of perceptual
      bias presumably reflecting the tendency to first inspect the side of the face
      better suited to face analysis (left side of face/right hemisphere). On top of
      this though, there was a relationship between response and fixation pattern. On
      trials where participants showed a left perceptual bias they produced
      significantly more left saccades and fixated for longer on the left. In contrast,
      for trials where participants showed a right perceptual bias there was no
      reliable difference between the number, or total fixation duration, on the left
      or the right. These results demonstrate that on a trial-by-trial basis subtle
      differences in the extent of left or right side scanning are related to the
      perceptual response of the participant, although an overall initial fixation bias
      to the left occurs irrespective of response bias.

PMID- 15488906
TI  - Loss of high-level perceptual knowledge of object structure in DAT.
AB  - Visual object recognition and naming deficits in patients with dementia of the
      Alzheimer type (DAT) have typically been attributed to deficits in semantic
      processing. On a visual object naming test, a group of 10 mild, early stage DAT
      patients (mean MMSE=23.8) were found to suffer from anomia, compared to a group
      of 10 age-matched control participants. DAT naming errors were typically within
      category (commission), associative or circumlocutory errors. Performance on tests
      of low level visuo-spatial ability fell within the normal range. Together these
      results suggested that anomia resulted from a dysfunctional semantic system with
      intact visual perception. However, in a naming task using visually degraded
      images of familiar objects, the recognition threshold in DAT patients was
      significantly higher, indicating the need for a more visually complete object
      representation, before it could be accurately recognised. In a matched task using
      words visually degraded in an identical manner, the recognition threshold for DAT
      patients was very similar to that of the control group. It is argued that these
      results support the idea that impaired structural descriptions of objects (i.e.,
      pre-semantic representation of an object within the visual perceptual system)
      combines with degraded semantic representations to produce anomia in mild early
      stage DAT.

PMID- 15488907
TI  - Category-related activation for written words in the posterior fusiform is task
      specific.
AB  - Category-related brain activations have been reported in the posterior fusiform
      gyri when people view pictures of tools and animals, but only a single study has
      observed this pattern when the stimuli were words, rather than pictures. Here we
      replicate these category effects with words and provide evidence that distinctive
      patterns of activation are task specific. The results suggest that category
      related activation in the posterior fusiform gyri can be driven either "bottom
      up" by visual processing of images or "top-down" by word processing.

PMID- 15488908
TI  - Reduced endogenous control in alien hand syndrome: evidence from naturalistic
      action.
AB  - Patients with alien hand (AH) syndrome from medial frontal lesions exhibit
      involuntary but seemingly purposeful contralesional upper limb movements. Two
      observations about AH patients have received little, if any, experimental
      confirmation. The first is that AH is triggered opportunistically by nearby
      objects. The second is that AH behaviors are increased in conditions of fatigue
      or anxiety, i.e. under reduced attentional control. A prominent account explains
      AH as reduced intention-driven (endogenous) executive control. This account
      predicts that erroneous AH behaviors should be driven by environmental (i.e.
      exogenous) factors, such as distractor proximity to the hand. AH errors should be
      less influenced by the intention or action plan (i.e. endogenous factors), such
      as the semantic relatedness of distractors to targets. Moreover, due to capacity
      limitations of the endogenous controller, AH behaviors should increase under
      conditions of secondary task load. We tested these predictions with an AH patient
      in two experiments using a naturalistic coffee-making task. Experiment 1
      demonstrated that the affected hand was highly perseverative and strongly
      influenced by exogenous but not endogenous factors. The non-alien hand made fewer
      errors. Experiment 2 showed that there was a disproportionate increase in
      perseverations and exogenous errors of the affected hand under secondary task
      load. The non-alien hand was significantly less disrupted by dual task
      conditions. These data provide experimental support for previous anecdotal
      observations about AH behavior in naturalistic settings, and are consistent with
      a unilateral defect in endogenous control.

PMID- 15488909
TI  - The inhibition of imitative and overlearned responses: a functional double
      dissociation.
AB  - Neuropsychological research has established that the inhibition of dominant
      response tendencies is a function of the prefrontal cortex. These inhibitory
      mechanisms are tested using tasks like the Stroop task, in which the prepotency
      of the dominant response is based on a learned relationship of stimulus and
      response. However, it has also been reported that patients with prefrontal
      lesions may have problems inhibiting imitative responses. The question arises of
      whether the inhibition of overlearned and imitative responses entails the same or
      different functional mechanisms and cortical networks. In a recent
      neuropsychological study with prefrontal patients we found first evidence for
      such a dissociation. The present fMRI study further investigated this question by
      directly comparing brain activity in the inhibition of overlearned and imitative
      response tendencies. It emerges that response inhibition in the two tasks
      involves different neural networks. While the inhibition of overlearned responses
      requires a fronto-parietal network involved in interference control and task
      management, the inhibition of imitative responses involves cortical areas that
      are required to distinguish between self-generated and externally triggered motor
      representations. The only frontal brain area that showed an overlap was located
      in the right inferior frontal gyrus and is probably related to the generation of
      the stop signal.

PMID- 15488910
TI  - Theory of mind after traumatic brain injury.
AB  - This study investigated whether people with severe traumatic brain injury (TBI)
      demonstrate a specific impairment on tasks requiring them to make inferences
      about others' mental states (theory of mind tasks). Participants with severe TBI
      were compared to a healthy group on verbal first-order and second-order theory of
      mind (ToM) tasks, non-verbal ToM tasks and on verbal and non-verbal tasks
      requiring them to make general (non-mental) inferences (NMIs). The clinical group
      performed more poorly than controls on both ToM and NMI tasks. This performance
      was not completely accounted for by the working memory or implicit language
      demands of the tasks. Multiple regression analyses suggested that patients with
      TBI have a general weakness in inference-making that, combined with linguistic
      and working memory limitations, impairs their performance on both non-verbal and
      second-order ToM tasks. However, a specific ToM impairment may underlie their
      poor performance on verbal first-order tasks. Implications of this finding for
      the possibility of a separate cognitive module of ToM are discussed, as well as
      for the rehabilitation of social deficits after TBI.

PMID- 15488911
TI  - An fMRI study of imitation: action representation and body schema.
AB  - Recent neuropsychological investigations of apraxia have led to new hypotheses
      about the representational defects associated with imitation impairments in
      neurological patients. This fMRI experiment investigated the relation between
      imitation and the body schema in healthy subjects. Experimental conditions were
      derived from a factorial plan, and participants were asked to watch a human model
      performing bodily gestures and then to execute either an identical or a different
      action, with the same or different limbs. Brain areas activated when subjects
      imitated the model were traced to the representation of the action (main effect
      of performing an identical action regardless of limb), to the body schema (using
      the same limb regardless of action), or to both. The first set of analyses
      yielded a network associated with visual perception, indicating that action
      representation is primarily visuospatial not motor, while the second analysis
      highlighted regions involved in body schema including the inferior parietal
      cortex and the insula. It is suggested that imitation of simple body gestures
      requires both a visuospatial description of the observed model, sustained by
      visual perception areas in the right occipitotemporal and superior parietal
      cortices and a visuospatial description of one's own body, supported by the left
      inferior parietal lobule. These results favor a model of praxis proposing that
      imitation deficits in left inferior parietal lobe patients with apraxia reflect
      primarily an impairment of the body schema, while deficits of praxis in right
      parietal patients are limited to gestures demanding in terms of visuospatial
      analysis.

PMID- 15488912
TI  - Hemispheric asymmetries and joke comprehension.
AB  - Joke comprehension deficits in patients with right hemisphere (RH) damage raise
      the question of the role of the intact RH in understanding jokes. One suggestion
      is that semantic, or meaning, activations are different in the RH and LH, and RH
      meanings are particularly important for joke comprehension. To assess whether
      hypothesized differences in semantic activation in the two hemispheres were
      relevant to joke comprehension, we recorded event-related brain potentials (ERPs)
      as healthy adults read laterally presented "punch words" to one-line jokes and
      nonjoke controls. Jokes presented to the RVF/LH elicited larger amplitude N400
      than the nonjoke endings; when presented to the LVF/RH, the joke and nonjoke
      endings elicited N400s of equal amplitude. This finding suggests that semantic
      activations in the two hemispheres do differ, with RH semantic activation
      facilitating joke comprehension.

PMID- 15488913
TI  - Word frequency and the lateralization of lexical processes.
AB  - Despite the extensive clinical and neuropsychological evidence for major
      differences in language function between the left and right hemispheres, it has
      proven difficult to demonstrate reliable differences in lexical processing. It is
      particularly surprising that frequency has been found to have no differential
      effects upon word recognition in the hemispheres, in view of the evidence that
      this variable has significant effects upon lexical processing. It is possible,
      however, that any interaction between word frequency and hemispheric processes is
      too subtle or too complex to be revealed by the simple dichotomous studies
      previously attempted. This study manipulated word frequency across seven levels
      in an effort to provide a fine-grained insight into the relationship between word
      frequency and lexical processing in the hemispheres. The results revealed a clear
      additivity between visual field and word frequency across all levels of
      frequency, for both RT and errors. Such findings create difficulties for the
      interpretation of studies of lateralized lexical access in general, and are
      particularly hard to reconcile with lateral asymmetries revealed in other aspects
      of lexical processing. It is proposed that a resolution of this problem may
      depend upon the development of theories that emphasise the notion of laterally
      distributed word representations, rather than discrete lexical structures on each
      side of the brain.

PMID- 15488914
TI  - Effects of oxalic acid on the regrowth of heterotrophic bacteria in the
      distributed drinking water.
AB  - Three laboratory-scale water pipe systems were set up to study the effects of
      adding oxalic acid on the bacterial regrowth and biofilm formation in the
      distributed drinking water. The results of water pipe experiment displayed that
      around 38% carbon in the oxalic acid could be converted to bacterial biomass. The
      maximum HPCs in biofilm were equal to 3.5x10(4), 3.38x10(5) and 2.8x10(6) CFUcm(
      2) while the maximum HPCs of free bacteria were equal to 1.2x10(3), 2.54x10(3)
      and 3.78x10(4) CFUml(-1) for the blank and with addition of 10 and 50 micrograms
      OA eq-Cl(-1), respectively. These results imply that the addition of oxalic acid
      to distributed water has positive effect on the assimilable organic carbon
      content of drinking water and bacterial regrowth in water pipe. This effect is
      enhanced with addition of high-level oxalic acid. Batch tests were also conducted
      using water samples collected from a Taiwanese drinking water distribution
      system. The bacterial regrowth potentials (BRPs) of the blank were equal to
      4.25x10(3), 1.46x10(4), 4.9x10(4) and 7.54x10(4) CFUml(-1) for water samples
      collected from treatment plant effluent, commercial area, mixed area, and
      residential area, respectively. These results show that the biological stability
      of distributed drinking water is the highest in treatment plant effluent, the
      moderate in the commercial area and mixed area, and the lowest in the residential
      area.

PMID- 15488915
TI  - Characterization of Cr ion exchange with hydrotalcite.
AB  - Experiments were performed to characterize the removal of chromium from water
      with uncalcined hydrotalcite, a clay mineral ion exchange media. The process was
      characterized as a function of pH, temperature, contact time, and both Cr and
      hydrotalcite concentrations. A Freundlich isotherm, used to describe adsorption
      equilibria, was used as a model and Freundlich constants were determined. The
      kinetics of the ion exchange reaction were also modeled using a pseudo-first
      order reaction rate. Finally, an equilibrium stage process was modeled with
      sequential batch separations to determine if hydrotalcite ion exchange could
      reduce aqueous Cr levels to below the EPA limit of 0.1mgl(-1). It was shown that
      the process is highly pH dependent, only yielding significant removals at pH
      levels between 2.0 and 2.1. While hydrotalcite concentration, Cr concentration,
      and time did effect the ion exchange, temperature was not found to be a factor.
      Under optimal conditions, maximum removals of greater than 95% were achieved.
      Finally, sequential batch tests performed on initial Cr solutions ranging from
      5mgl(-1) to 40mgl(-1), demonstrated that the water could be purified to a level
      that was not statistically different than the EPA limit, thus demonstrating the
      applicability of hydrotalcite ion exchange.

PMID- 15488916
TI  - Performance of photocatalytic reactors using immobilized TiO2 film for the
      degradation of phenol and methylene blue dye present in water stream.
AB  - TiO2 thin film photocatalyst was successfully synthesized and immobilized on
      glass reactor tube using sol-gel method. The synthesized TiO2 coating was
      transparent, which enabled the penetration of ultra-violet (UV) light to the
      catalyst surface. Two photocatalytic reactors with different operating modes were
      tested: (a) tubular photocatalytic reactor with re-circulation mode and (b) batch
      photocatalytic reactor. A new proposed TiO2 synthesized film formulation of 1
      titanium isopropoxide: 8 isopropanol: 3 acetyl acetone: 1.1 H2O: 0.05 acetic acid
      (in molar ratio) gave excellent photocatalytic activity for degradation of phenol
      and methylene blue dye present in the water. The half-life time, t1/2 of
      photocatalytic degradation of phenol was 56 min at the initial phenol
      concentration of 1000 microM in the batch reactor. In the tubular photocatalytic
      reactor, 5 re-circulation passes with residence time of 2.2 min (single pass)
      degraded 50% of 40-microM methylene blue dye. Initial phenol concentration,
      presence of hydrogen peroxide, presence of air bubbling and stirring speed as the
      process variables were studied in the batch reactor. Initial methylene blue
      concentration, pH value, light intensity and reaction temperature were studied as
      the process variables in the tubular reactor. The synthesized TiO2 thin film was
      characterized using SEM, XRD and EDX analysis. A comparative performance between
      the synthesized TiO2 thin film and commercial TiO2 particles (99% anatase) was
      evaluated under the same experimental conditions. The TiO2 film was equally
      active as the TiO2 powder catalyst.

PMID- 15488917
TI  - Heterogeneous photocatalysis of aromatic and chlorinated volatile organic
      compounds (VOCs) for non-occupational indoor air application.
AB  - The current study evaluated the technical feasibility of applying TiO2
      photocatalysis to the removal of low-ppb concentrations of volatile organic
      compounds (VOCs) commonly associated with non-occupational indoor air quality
      issues. A series of experiments was conducted to evaluate five parameters
      (relative humidity (RH), hydraulic diameter (HD), feeding type (FT) for VOCs,
      photocatalytic oxidation (PCO) reactor material (RM), and inlet port size (IPS)
      of PCO reactor) in relation to the PCO destruction efficiencies of the selected
      target VOCs. None of the target VOCs exhibited any significant dependence on the
      RH, which is inconsistent with a previous study where, under conditions of low
      humidity and a ppm toluene inlet level, a drop in the PCO efficiency was reported
      with a decreasing humidity. However, the other four parameters (HD, RM, FT, and
      IPS) were found to be important for better VOC removal efficiencies as regards
      the application of TiO2 photocatalytic technology for cleansing non-occupational
      indoor air. The PCO destruction of VOCs at concentrations associated with non
      occupational indoor air quality issues was up to nearly 100%, and the CO
      generated during PCO was a negligible addition to indoor CO levels. Accordingly,
      a PCO reactor would appear to be an important tool in the effort to improve non
      occupational indoor air quality.

PMID- 15488918
TI  - Leaching of lead metallurgical slag in citric solutions--implications for
      disposal and weathering in soil environments.
AB  - Metallurgical slags from primary lead smelting were submitted to a 30-day batch
      leaching procedure in 20 and 8 mM citric solutions in order to determine the
      kinetics of release of Pb, Cu, Zn and As. The experiment was coupled with the
      PHREEQC-2 speciation-solubility modelling and mineralogical study of newly formed
      products (SEM/EDS, XRD, TEM/EDS and Raman spectrometry). A strong scavenging of
      metals and metalloids from the 8 mM citric leachate was observed due to the
      formation of newly formed products. The secondary precipitate consisted of well
      developed calcite (CaCO3) crystals and amorphous organo-mineral matrix composed
      of hydrous ferric oxides and amorphous SiO2. Metals (Pb, Zn, Cu) and arsenic
      released into the solution were subsequently bound onto the newly formed product
      (adsorption on oxides) or trapped within the calcite structure (Zn, Mn). Similar
      scavenging mechanism can be taken into account in real soil systems with lower
      concentration of citric acid. Then, the covering of slag dumps with a thick soil
      layer and subsequent re-vegetation might be a possible scenario for slag
      management on some metallurgical sites.

PMID- 15488919
TI  - Chlorinated herbicide (triallate) dehalogenation by iron powder.
AB  - The reductive degradation of a chlorinated herbicide by iron powder was
      investigated at lab scale. The studied substrate was triallate (S-2,3,3
      trichloroallyl di-isopropyl thiocarbamate) which contains a trichloroethylene
      moiety potentially reducible by zero-valent iron. Degradation reactions were
      carried out in batch, at 25 degrees C, in the absence of oxygen, by contacting
      electrolytic iron powder (size range: 20-50 microm) with a triallate aqueous
      solution (2.5 mgl(-1)). Herbicide decay, corresponding evolutions of TOC, TOX and
      chloride ion release were regularly monitored throughout the reactions.
      Furthermore, the main degradation by-products were identified by HPLC/MS. The
      results showed that, after 5 days, herbicide degradation extent was about 97% and
      that the reaction proceeded through the formation of a dechlorinated alkyne by
      product (S-2-propinyl di-isopropyl thiocarbamate) resulting from the complete
      dechlorination of triallate. The subsequent reduction of such an alkyne
      intermediate gave S-allyl di-isopropyl thiocarbamate as main end by-product. The
      identified by-products suggested that dechlorination took place mainly via
      reductive beta-elimination. However, as traces of dichloroallyl di-isopropyl
      thiocarbamate were also detected, a role, although minor, was assigned even to
      hydrogenolysis in the overall dechlorination process.

PMID- 15488920
TI  - Electroassisted methods for waste destruction: silver(II) and peroxydisulfate
      reagents in the electrochemically mediated oxidation of polyaromatic sulfonates.
AB  - The electrochemical oxidation is a promising process for organic pollutants which
      are recalcitrant to biological degradation. The anodic oxidation of 1,5
      naphthalenedisulfonic acid, hereafter NDS, was evaluated at a Pt anode using in
      situ generated Ag(II) cation or peroxydisulfate [S2O(8)(2-)] anion as mediators.
      Kinetics of the direct chemical oxidation of NDS in the presence of Na2S2O8, and
      the identification of some oxidation intermediates are also reported. An analysis
      of the results shows that Ag(II) is characterized by a high-reaction rates, while
      [S2O(8)(2-)] performs the oxidation of NDS in a complete way.

PMID- 15488921
TI  - Degradation of dyes in aqueous solutions by the Fenton process.
AB  - Degradation of 20 different dyes in aqueous solutions by the Fenton process was
      performed. These dyes include 6 types: acidic, reactive, direct, cationic,
      disperse and vat dyes. The former four types of dyes were decolorized and their
      TOC values were decreased greatly, while the color and TOC removals of the latter
      two types were lower. The catalytic activities of four metal ions on the
      degradation efficiencies of Vat Blue BO, which was chosen as a model dye because
      of its lowest color and TOC removals, were compared in the dark and under the
      ultraviolet light irradiation. The catalytic ability of different metals was
      Fe2+>Cu2+>Mn2+>Ag+ in the dark, and the same sequence was obtained under
      irradiation condition with greater degradation efficiency. Furthermore, the
      efficiencies of three oxidation processes, including H2O2/UV, Fe2+/H2O2 and
      Fe2+/H2O2/UV were compared. The results showed that the oxidation by Fe2+/H2O2/UV
      was the strongest, and even greater than the arithmetic sum of the other two
      processes, which suggests the synergistic effect of ultraviolet and ferrous ions
      on the degradation reaction.

PMID- 15488922
TI  - Comparison of azo dye degradation efficiency using UV/single semiconductor and
      UV/coupled semiconductor systems.
AB  - This study examined degradation of azo dyes using photocatalytic oxidation
      (UV/semiconductor). The model substrates employed in this work were Procion Red
      MX-5B and Amaranth, while the photocatalysts were TiO2, ZnO, and SnO2. UV-Vis
      spectrum analysis demonstrated that the band gap energies of TiO2, ZnO, and SnO2
      were 3.17, 2.92, and 4.13 eV, respectively. The band gap energy of SnO2 is
      insufficient to initiate photocatalytic reaction after UV irradiation (365 nm).
      The reaction rate constants fit a first-order reaction model and the reaction
      rate constant of Procion Red MX-5B for TiO2+SnO2 (0.31 h-1) is larger than that
      of TiO2 (0.24 h-1) and SnO2 at pH 10. The difference between the conduction bands
      of SnO2 and TiO2 enables the former to act as a sink for the photogenerated
      electrons. Most of the reaction rate constants had higher values at pH 10 than pH
      7, and thus the OH attack could be assumed to represent the main reaction in this
      investigation. The quantities of sulfate and chloride ions released are below
      stoichiometry during the degradation. Owing to the sulfonate groups of Amaranth
      exceeding Procion Red MX-5B, Amaranth had larger electrostatic attraction than
      Procion Red MX-5B with the surface of ZnO, and also had higher adsorption
      percentage than Procion Red MX-5B on the surface of ZnO. The trend of adsorption
      is consistent with the reaction rate constant at pH 7, namely Amaranth>Procion
      Red MX-5B. The sulfate dissociation rate constant of Amaranth in UV/ZnO at pH 7
      (0.49 h-1) approaches the overall rate constant (0.53 h-1); therefore, the first
      step involved in Amaranth can be suggested to the cleavage of the bonds of the C
      S in Amaranth, causing sulfate ion formation.

PMID- 15488923
TI  - Reduction of hexavalent chromium by ascorbic acid in aqueous solutions.
AB  - Hexavalent chromium is a priority pollutant in the USA and many other countries.
      Reduction of Cr(VI) to Cr(III) is environmentally favorable as the latter species
      is not toxic to most living organisms and also has a low mobility and
      bioavailability. Reduction of Cr(VI) by ascorbic acid (vitamin C) as a reductant
      was studied using potassium dichromate solution as the model pollutant. Effects
      of concentration of vitamin C, pH, temperature, irradiation and reaction time on
      the reduction of Cr(VI) were examined. Cr(VI) might be reduced by vitamin C not
      only in acidic conditions but also in weakly alkaline solutions. The reduction of
      Cr(VI) by vitamin C might occur not only under irradiation but also in the dark.
      Vitamin C is an important biological reductant in humans and animals, and not
      toxic. It is water-soluble and can easily permeate through various types of
      soils. The results indicate that vitamin C could be used in effective remediation
      of Cr(VI)-contaminated soils and groundwater in a wide range of pH, with or
      without sunlight.

PMID- 15488924
TI  - Semivolatile and volatile compounds in combustion of polyethylene.
AB  - The evolution of semivolatile and volatile compounds in the combustion of
      polyethylene (PE) was studied at different operating conditions in a horizontal
      quartz reactor. Four combustion runs at 500 and 850 degrees C with two different
      sample mass/air flow ratios and two pyrolytic runs at the same temperatures were
      carried out. Thermal behavior of different compounds was analyzed and the data
      obtained were compared with those of literature. It was observed that alpha,omega
      olefins, alpha-olefins and n-paraffins were formed from the pyrolytic
      decomposition at low temperatures. On the other hand, oxygenated compounds such
      as aldehydes were also formed in the presence of oxygen. High yields were
      obtained of carbon oxides and light hydrocarbons, too. At high temperatures, the
      formation of polycyclic aromatic hydrocarbons (PAHs) took place. These compounds
      are harmful and their presence in the combustion processes is related with the
      evolution of pyrolytic puffs inside the combustion chamber with a poor mixture of
      semivolatile compounds evolved with oxygen. Altogether, the yields of more than
      200 compounds were determined. The collection of the semivolatile compounds was
      carried out with XAD-2 adsorbent and were analyzed by GC-MS, whereas volatile
      compounds and gases were collected in a Tedlar bag and analyzed by GC with
      thermal conductivity and flame ionization detectors.

PMID- 15488925
TI  - Micellar-enhanced ultrafiltration process (MEUF) for removing copper from
      synthetic wastewater containing ligands.
AB  - The effects of the type and concentration of ligands on the removal of Cu by
      micellar-enhanced ultrafiltration (MEUF) with the help of either anionic or
      cationic surfactants were investigated. The removal efficiency of copper by
      anionic surfactant-(SDS-) MEUF depends on the ligand-to-Cu ratio and the ligand
      to-Cu complexation constant. At fixed ligand-to-Cu ratio, the Cu removal
      efficiency decreases in the order of citric acid>NTA>EDTA, which is the reverse
      order of Cu-ligand complexation constants for these ligands. Increasing SDS
      ligand ratios from 12 to 60 at fixed ligand concentration did not improve copper
      removal efficiency. The cationic surfactant, CPC, enhances Cu removal efficiency
      in systems with condition of ligand-copper ratios higher than 1.0, where Cu
      removal is not very efficient using SDS-MEUF process. The Cu removal efficiency
      with CPC-MEUF depends on both the ligand-to-Cu ratio and the type of ligands.

PMID- 15488926
TI  - Photocatalytic removal of fenitrothion in pure and natural waters by photo-Fenton
      reaction.
AB  - The photocatalytic removal kinetics of fenitrothion at a concentration of 0.5mgl(
      1) in pure and natural waters were investigated in Fe(III)/H2O2/UV-Vis,
      Fe(III)/UV-Vis and H2O2/UV-Vis oxidation systems, with respect to decreases in
      fenitrothion concentrations with irradiation time using a solar simulator.
      Fenitrothion concentrations were determined by HPLC analysis. Furthermore, total
      mineralization of fenitrothion in these systems was evaluated by monitoring the
      decreases in DOC concentrations with solar simulator irradiation time by TOC
      analysis. It was shown that the degradation rate of fenitrothion was much faster
      in the Fe(III)/H2O2/UV-Vis system than the Fe(III)/UV-Vis and H2O2/UV-Vis systems
      in both pure and river waters. Consequently, the mineralization rate of
      fenitrothion was much faster in the Fe(III)/H2O2/UV-Vis system than in the other
      two systems. The high *OH generation rate measured in the Fe(III)/H2O2/UV-Vis
      system was the key to faster degradation of fenitrothion. Increases in the
      concentrations of H2O2 and Fe led to better final degradation of fenitrothion.
      These results suggest that the photo-Fenton reaction (Fe(III)/H2O2/UV-Vis) system
      is likely to be an effective method for removing fenitrothion from contaminated
      natural waters.

PMID- 15488927
TI  - Using solar and ultraviolet light to degrade PCBs in sand and transformer oils.
AB  - The present study describes the effect of the operating variables in the
      sensitized solar photolysis of sandy sediments contaminated by polychlorinated
      biphenyls (PCBs) in alkaline isopropanol. PCBs were almost completely removed in
      two weeks with stoichiometric release of chloride and biphenyl (BP) by a
      mechanism of reductive dechlorination. The concentration of the sensitizer
      (acetone) was the variable found to have most influence on the process. Under the
      same conditions, only partial dechlorination of the PCBs (34%) was observed in
      dielectric fluids without generating biphenyl to any appreciable extent. Direct
      photolysis (ultraviolet light at 254nm) of dielectric oils dissolved in alkaline
      isopropanol lead to 92% removal of PCBs in 60min. The observed mechanism was
      again that of reductive dechlorination, with stoichiometric release of chloride,
      and the accumulation of biphenyl, quaterphenyl and condensation products of
      biphenyl with isopropanol.

PMID- 15488928
TI  - Washing of Pb contaminated soil using [S,S] ethylenediamine disuccinate and
      horizontal permeable barriers.
AB  - The feasibility of in situ washing of soil contaminated with Pb (6.83 mmol kg(
      1)) using biodegradable chelator, [S,S] stereoisomere of ethylenediamine
      disuccinate ([S,S]-EDDS) and horizontal permeable barriers was examined in soil
      columns. After 4-cycles of 10 mmol kg(-1) soil [S,S]-EDDS applications, followed
      by irrigation, 24.7% of total initial Pb was washed from the contaminated soil
      and accumulated into the barrier. Sequential extractions indicated that washing
      removed most of the Pb from the organic soil fraction. Barriers were positioned
      20 cm deep in the soil and consisted of a 2 cm layer of nutrient enriched
      vermiculite. Barriers reduced leaching of Pb in the first cycle of [S,S]-EDDS
      addition by more than 500-times compared to columns with no barrier. After four
      cycles of chelator addition, a total of 0.24% of the initial Pb was leached from
      the columns with barriers. Four cycles of in situ soil washing in soil columns
      were less effective than simulated ex situ soil washing with 40 mmol kg(-1) [S,S]
      EDDS, where 51.0% of the Pb was removed after 48-h extraction. Ex situ soil
      washing with 10 mmol kg(-1) [S,S]-EDDS was equally effective as the first cycle
      of in situ soil washing (15.5% and 14.5% of removed Pb, respectively).

PMID- 15488929
TI  - Photochemical and photocatalytic degradation of gaseous toluene using short
      wavelength UV irradiation with TiO2 catalyst: comparison of three UV sources.
AB  - The feasibility of the use of short-wavelength UV (254+185 nm) irradiation and
      TiO2 catalyst for photodegradation of gaseous toluene was evaluated. It was clear
      that the use of TiO2 under 254+185 nm light irradiation significantly enhanced
      the photodegradation of toluene relative to UV alone, owed to the combined effect
      of photochemical oxidation in the gas phase and photocatalytic oxidation on TiO2.
      The photodegradation with 254+185 nm light irradiation was compared with other UV
      wavelengths (365 nm (black light blue lamp) and 254 nm (germicidal UV lamp)). The
      highest conversion and mineralization were obtained with the 254+185 nm light.
      Moreover, high conversions were achieved even at high initial concentrations of
      toluene. Catalyst deactivation was also prevented with the 254+185 nm light.
      Regeneration experiments with the deactivated catalyst under different conditions
      revealed that reactive oxygen species played an important role in preventing
      catalyst deactivation by decomposing effectively the less reactive carbon
      deposits on the TiO2 catalyst. Simultaneous elimination of photogenerated excess
      ozone and residual organic compounds was accomplished by using a MnO2 ozone
      decomposition catalyst to form reactive species for destruction of the organic
      compounds.

PMID- 15488930
TI  - Influence of the application of sewage sludge on the degradation of pesticides in
      the soil.
AB  - A study was made of the influence of the application of sewage sludge on the
      degradation of pesticides in the soil. Two kinds of sludge were used, with
      different characteristics, one from an urban treatment plant and one from a food
      processing plant. Three organophosphorus insecticides, fenitrothion, diazinon and
      dimethoate, were studied. The relative importance was determined of the chemical
      and biological degradation processes, which involved experiments on soil and
      sterile soil samples. A comparative study was also made of the degradation of
      pesticide residues and the evolution of the microbial population. The application
      of sludge seems to have a complex effect on the degradation of pesticides,
      determined by the bioavailability and biodegradability of their active
      ingredient. The biodegradation of pesticide residues brings about alterations in
      the microorganism population of the soil.

PMID- 15488931
TI  - Use of biomass sorbents for oil removal from gas station runoff.
AB  - The use of biomass sorbents, which are less expensive and more biodegradable than
      synthetic sorbents, for oil removal from gas station runoff was investigated. A
      bench-scale flume experiment was conducted to evaluate the oil removal and
      retention capabilities of the biomass sorbents which included kapok fiber,
      cattail fiber, Salvinia sp., wood chip, rice husk, coconut husk, and bagasse.
      Polyester fiber, a commercial synthetic sorbent, was also experimented for
      comparison purpose. Oil sorption and desorption tests were performed at a water
      flow rate of 20 lmin-1. In the oil sorption tests, a 50 mgl(-1) of used engine
      oil-water mixture was synthesized to simulate the gas station runoff. The mass of
      oil sorbed for all sorbents, except coconut husk and bagasse, was greater than
      70%. Cattail fiber and polyester fiber were the sorbents that provided the least
      average effluent oil concentrations. Oil selectivity (hydrophobic properties) and
      physical characteristics of the sorbents are the two main factors that influence
      the oil sorption capability. The used sorbents from the sorption tests were
      employed in the desorption tests. Results indicated that oil leached out of all
      the sorbents tested. Polyester fiber released the highest amount of oil,
      approximately 4% (mass basis) of the oil sorbed.

PMID- 15488932
TI  - A method to estimate emission rates from industrial stacks based on neural
      networks.
AB  - This paper presents a technique based on artificial neural networks (ANN) to
      estimate pollutant rates of emission from industrial stacks, on the basis of
      pollutant concentrations measured on the ground. The ANN is trained on data
      generated by the ISCST3 model, widely accepted for evaluation of dispersion of
      primary pollutants as a part of an environmental impact study. Simulations using
      theoretical values and comparison with field data are done, obtaining good
      results in both cases at predicting emission rates. The application of this
      technique would allow the local environment authority to control emissions from
      industrial plants without need of performing direct measurements inside the
      plant.

PMID- 15488933
TI  - Effects of cross-substrate interaction on biotrickling filtration for the control
      of VOC emissions.
AB  - The effects of cross-substrate interaction to the performance of a gas-phase
      biotrickling filter for treating a mixture of volatile organic compounds (VOCs),
      including three structural heterologous in acetone, toluene, and
      trichloroethylene, were investigated. The biotrickling filter was inoculated with
      microbial consortium containing at least seven bacterial species utilizing either
      acetone or toluene, or both, as their carbon sources. In the performance study,
      the column operating under variable conditions typifying the waste gas emission
      from the microelectronics fabrication processes achieved a total hydrocarbon
      (THC) removal efficiency in excess of 85% and a mineralization capacity over 50%
      for THC mass loading as high as 36.2 g-CH4 m-3h-1. The cross-substrate effects
      were examined by correlating the relative changes in the mass removal of each
      substrate with the biodegradative capability of the microbial consortium. The
      degradation of trichloroethylene was primarily due to co-metabolism by the
      toluene-oxidizing enzymes, but the results also indicated that trichloroethylene
      partially induced its own degradation. Concentration increases in acetone
      appeared to cause a diauxie effect that suppressed degradation of toluene and
      trichloroethylene, and shifted the microbial population toward the selective
      acetone-degraders. No irrecoverable toxicity or inhibitory effects were observed
      throughout the experiments. These results suggest that the relative VOC
      concentration in the waste gas mixture is a factor as important as the
      biodegradative function of the microbial consortium, and thus should be carefully
      evaluated to satisfy the treatment objectives.

PMID- 15488934
TI  - Phenol removal from high salinity effluents using Fenton's reagent and photo
      Fenton reactions.
AB  - The removal of pollutants in saline medium by the Fenton's reagent needs a more
      detailed investigation, since the presence of chloride may inhibit or retard
      degradation. Phenol was used as a model pollutant and the influence of some
      important process variables for the removal of total organic carbon and phenol
      were investigated, such as FeSO4 and H2O2 concentrations, pH and salinity. The
      reactivity of iron cations and alternative procedures of applying UV radiation
      (photo-Fenton) were evaluated. Phenol was fast and completely removed by the
      Fenton's process even in a high saline medium (50,000mg NaCll(-1)). However, TOC
      was only moderately or poorly removed in saline media, depending on the salt
      concentration. When the photo-Fenton process was used, mineralization was
      improved and high TOC removals were observed in moderately saline media (NaCl
      concentration < or =10,000mgl(-1)). For the highest NaCl concentration tested
      (50,000mgl(-1)) only a moderate TOC removal was observed (50%).

PMID- 15488935
TI  - Effect of gas velocity and influent concentration on biofiltration of gasoline
      off-gas from soil vapor extraction.
AB  - This study was conducted to evaluate the effects of gas inlet concentration and
      velocity on the biofiltration of gasoline vapor. Gasoline vapor was treated using
      a compost biofilter operated in an upflow mode for about 3 months. The inlet
      concentration of gasoline total petroleum hydrocarbon (TPH) ranged from about 300
      to 7000 mgm(-3) and gas was injected at velocities of 6 and 15 mh(-1) (empty bed
      residence time (EBRT)=10 and 4 min, respectively). The maximum elimination
      capacities of TPH at 6 and 15 mh(-1) found in this research were over 24 and 19
      gm(-3) of filling material h(-1), respectively. TPH removal data was fit using a
      first-order kinetic relationship. In the low concentration range of 300-3000 mg
      m(-3), the first-order kinetic constants varied between about 0.10 and 0.29 min(
      1) regardless of gas velocities. At TPH concentrations greater than 3000 mgm(-3),
      the first-order kinetic constants were about 0.09 and 0.07 min(-1) at gas
      velocities of 6 mh(-1) and 15 mh(-1), respectively. To evaluate microbial
      dynamics, dehydrogenase activity, CO2 generation and microbial species diversity
      were analyzed. Dehydrogenase activity could be used as an indicator of microbial
      activity. TPH removal corresponded well with CO2 evolution. The average CO2
      recovery efficiency for the entire biofilter ranged between 60% and 70%. When the
      gas velocity was 6 mh(-1), most of the microbial activity and TPH removal
      occurred in the first quarter of the biofilter. However, when the gas velocity
      was 15 mh(-1), the entire column contributed to removal. Spatial and temporal
      variations in the biofilter microbial population were also observed. Nearly 60%
      of the colonies isolated from the compost media prior to biofiltration were
      Bacillus. After 90 days of biofiltration, the predominant species in the lower
      portion (0-50 cm) of the filter were Rhodococcus, while Pseudomonas and
      Acinetobacter dominated the upper portion (75-100 cm).

PMID- 15488936
TI  - Biodegradability oriented treatability studies on high strength segregated
      wastewater of a woolen textile dyeing plant.
AB  - Textile dyeing and finishing industry involves considerable amount of water usage
      as well as polluted and highly colored wastewater discharges. Biological
      treatability by means of mineralization, nitrification and denitrification of
      high strength woolen textile dye bathes, first- and second-rinses is presented.
      COD fractionation study was carried out and kinetic parameters were determined.
      Biodegradability of organic compounds in highly loaded composite wastewater after
      segregation and the effluent of applied biological treatment of high strength
      composite wastewater were measured by determining oxygen consumption rates. The
      results were used in terms of assessing an alternative method for inert COD
      fractionation. The study implied that about 80% soluble COD, 50% color and 75%
      toxicity reduction were possible by single sludge biological processes. Sixteen
      per cent of total COD was found to be initially inert. Inert fraction was
      increased to 22% by production of soluble and particulate microbial products
      through biological treatment.

PMID- 15488937
TI  - Photosensitized degradation of Irgarol 1051 in water.
AB  - Irgarol 1051 (2-methylthio-4-tert-butylamino-6-cyclopropylamino-s-triazine) is a
      herbicide analogue that is added to antifouling agents used on ships. Our former
      study on its degradation in sunlight suggested that unknown photosensitizers in
      natural waters accelerated the photodegradation to the degradation product, M1.
      In this study, the photodegradation of Irgarol in water was investigated in the
      presence of some photosensitizers. Test water containing Irgarol or M1, with or
      without photosensitizers, was irradiated with light from a UV-A fluorescent lamp
      for 48h. The concentrations of Irgarol and M1 in the test water were determined
      by HPLC after solid-phase extraction. M1 was more stable than Irgarol when
      irradiated in the presence of photosensitizers such as acetone, benzophenone,
      tryptophan, and rose bengal. Hydrogen peroxide (HP) accelerated the
      photodegradation of Irgarol, and the product M1 was degraded in the presence of
      more than 100mgl(-1) HP after 10h. Natural humic substances (NHS) also
      accelerated the photodegradation of Irgarol, but in this case, the product M1
      persisted even when Irgarol was completely degraded. Photosensitized degradation
      of Irgarol by NHS may result in the accumulation of M1 in aquatic environments.

PMID- 15488938
TI  - Molecular cloning and expression analysis of a macrophage-colony stimulating
      factor receptor-like gene from rainbow trout, Oncorhynchus mykiss.
AB  - The M-CSF and its receptor (M-CSFR, CSF-1R or c-fms proto-oncogene) system were
      initially implicated as essential in mammals for normal monocyte development as
      well as for pregnancy. To allow a comparison with the M-CSF and M-CSFR system of
      an oviparous animal, we cloned a M-CSFR-like gene from rainbow trout
      (Oncorhynchus mykiss). The gene was cloned from a cDNA library of head kidney. It
      contained an open reading frame encoding 967 amino acids with a predicted size of
      109 kDa. The putative amino acid sequence of rainbow trout M-CSFR showed 54%
      amino acid identity to fugu (Takifugu rubripes) M-CSFR, 52% to zebrafish (Danio
      rerio) M-CSFR and 40% to mouse (Mus musculus) and human (Homo sapiens) M-CSFR.
      The M-CSFR-like gene was constitutively expressed in head kidney, kidney,
      intestine, spleen and blood. The gene was detected especially in the ovary of
      immature female rainbow trout. These results suggest that a M-CSFR-like receptor
      may be involved in female reproductive tracts even in an oviparous animal like
      fish.

PMID- 15488939
TI  - Conformational changes in the antibody constant domains upon hapten-binding.
AB  - Bacterial proteins A and G (SpA and SpG) are immunoglobulin receptors that can be
      used as probes for monitoring change in the conformation of heavy chain constant
      (C(H)) domains. Interaction of anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibody
      (Ab) with SpA and SpG were measured by isothermal titration calorimetry and
      surface plasmon resonance in order to address the question of whether hapten
      binding induces a conformational change in the C(H) domain. The interactions of
      IgG2a or its enzymatic fragments with SpA were measured in the presence or
      absence of the hapten. Although binding of Fab and F(ab')2 fragments were not
      observed to free SpA, they did bind to immobilized SpA. In addition, the
      association constant (K(a)) for interaction of IgG2a with immobilized SpA was
      approximately 20-fold higher than that with free SpA. This was explained in terms
      of high avidity resulting from multivalent interaction between IgG2a and
      immobilized SpA on the chip. Interestingly, the hapten-binding weakened the
      interaction between the F(ab')2 fragment and SpA. Furthermore, approximately half
      of the IgG2a was incapable of binding to immobilized SpA in the presence of
      hapten. These results were explained using a model which assumed the formation of
      two kinds of SpA/IgG complexes; one through sites on F(ab')2 arms and the other
      through sites on the Fc region. The former type dissociated as a result of hapten
      binding, as did the F(ab')2 fragment and suggested that a conformational change
      had occurred around the Fab arms, while the latter type did not dissociate
      because of the higher avidity of the Fc region. However, using a mutant SpA with
      a lower K(a) value for the interaction with IgG2a, it was shown that hapten
      binding induced long range conformational changes in the Fc region of IgG2a.
      Similar evidence of conformational change upon hapten-binding was also obtained
      using SpG as a probe.

PMID- 15488940
TI  - Evidence that negative feedback between antibody concentration and affinity
      regulates humoral response consolidation to a non-infectious antigen in infants.
AB  - The dynamics of human antigen-specific immunoglobulin (Ig) responses in early
      life are not well characterized. We have previously observed an inverse
      relationship between allergen-specific Ig concentration and allergen-Ig-binding
      affinity in allergen-sensitive atopic adults, suggesting a possible feedback
      relationship between these variables. We prospectively studied children (6 months
      to 6 years) with and without atopic sensitization to the Der p 1 major allergen.
      Experimental results showed the following trends. (1) In both study groups, there
      was little change with age in average Der p 1-specific Ig (IgG1 or IgE)
      concentrations or allergen-Ig-binding affinities, and concentrations and
      affinities were independent. (2) Among individuals, however, there was a negative
      correlation between Ig concentration changes and affinity changes with age. (3)
      The rate of increase with age of the non-atopic Der p 1-IgG1 total binding
      capacity (Ig concentration x Ig affinity) paralleled that for the atopic Der p 1
      IgE total binding capacity, and there was a comparable 'consolidation' of
      responses with age reflected by a narrowing of the variance of total binding
      capacity values. Except for the Ig classes involved, development of a humoral
      response to a non-infectious allergen is similarly regulated in atopic and non
      atopic children, with Ig total binding capacity as the key regulatory variable.
      These results also suggest that there is a time-dependent feedback relationship
      between Ig concentrations and affinities that establishes an optimal Ig total
      binding capacity for a given environmental 'antigen load'. A theoretical model is
      proposed to account for this relationship.

PMID- 15488941
TI  - Investigation of the mechanisms of anti-complement activity in Ixodes ricinus
      ticks.
AB  - The feeding success of a tick upon a host depends on its ability to suppress host
      anti-tick responses which include activation of the complement system. We
      investigated the mechanism of inhibition of the alternative pathway of complement
      by salivary gland extract (SGE) of the ixodid tick species, Ixodes ricinus. SGE
      treatment strongly inhibited C3a generation and factor B cleavage in serum when
      rabbit erythrocytes were used as complement activator, but not when cobra venom
      factor (CVF) was used as an activator. SGE treatment strongly inhibited C3b
      deposition on rabbit erythrocytes, and the turnover of C3 (to C3b/iC3b) in serum.
      However, there was no significant effect upon the formation, stability or
      activity of C3 convertase (C3bBb) when formed from purified C3b, factor B and
      factor D. SGE treatment of isolated C3 resulted in a shift in mobility of the
      alpha-chain (by about 5 kDa). N-terminal sequencing of this species suggests that
      cleavage occurs at the C-terminus of the alpha-chain of C3. Consistent with this
      hypothesis, the modified alpha-chain was still a substrate for pre-formed
      convertase. The activity was specific for the alpha-chain of C3 but not of
      C3(H2O) nor the alpha'-chain of C3b. It is proposed that SGE-modified C3 does not
      participate in convertase formation, probably having a reduced affinity for
      factor B.

PMID- 15488942
TI  - Beta-2-glycoprotein specificity of human anti-phospholipid antibody resides on
      the light chain: a novel mechanism for acquisition of cross-reactivity by an
      autoantibody.
AB  - We have recently shown that the anti-cardiolipin activity of human anti
      phospholipid antibody UK4 (lambda) resides on its heavy chain. We now show that
      UK4 possesses strong reactivity to the plasma-protein beta2-Glycoprotein I (beta2
      GPI) also. Utilizing chain shuffling experiments involving an unrelated anti-p185
      antibody 4D5 (kappa) with no reactivity to beta2-GPI, we now demonstrate that
      both the constructs possessing the auto-antibody-derived light chain exhibited
      significant binding to beta2-GPI. However, the construct possessing UK4 heavy
      chain in association with 4D5 light chain, exhibited no anti-beta2-GPI activity.
      Furthermore, there was a low increase (approximately 10%) in the binding of UK4
      to cardiolipin in the presence of beta2-GPI. The results demonstrate that anti
      beta2-GPI activity resides on UK4 light chain and, importantly, this activity
      could be transferred to a novel antibody construct via the light chain alone.
      Computer-generated models of the three-dimensional structures of UK4 and its
      hybrids, suggest predominant interaction of UK4 light chain with domain IV of
      beta2-GPI. Molecular docking experiments highlight a number of potential sites on
      beta2-GPI for interaction of UK4 and indicate as to how beta2-GPI recognition may
      occur primarily via the autoantibody light chain. The study provides first
      demonstration of the occurrence of anti-phospholipid and anti-beta2-GPI
      activities separately on heavy and light chains of an autoantibody. The possible
      mechanisms that such antibodies may employ to recognise their antigens, are
      discussed.

PMID- 15488943
TI  - The murine thymic stromal lymphopoietin receptor is partially expressed with an
      extracellular C-terminus.
AB  - The gene encoding the murine thymic stromal lymphopoietin receptor was expressed
      in lepidopteran insect cells using the baculovirus expression vector system. The
      corresponding gene was inserted under the polyhedrin promoter of the Autographa
      californica Nuclear Polyhedrosis Virus and expressed with an N-terminal poly
      histidine tag and a C-terminal FLAG-tag in the Spodoptera frugiperda insect cell
      line Sf9 during viral infection. Flow cytometer analysis of cells infected with
      the produced recombinant virus FastBacHisB-mdelta1-FLAG demonstrated that a
      majority of the infected cells expressed the mTSLPR with an extracellular C
      terminal end. A similar observation was noticed in COS cells transfected with
      pSVL-mTSLPR-FLAG. Immunoblotting with monoclonal anti-FLAG or anti-his antibodies
      indicated that the corresponding receptor protein migrated as an approximately 50
      kDa protein. mTSLPR produced in presence of tunicamycin migrated with a molecular
      weight around 40 kDa. The genetically fused poly-histidine tag was also
      demonstrated to be functional using a Ni-NTA purification system, indicating this
      protein otherwise to have normal biochemical properties.

PMID- 15488944
TI  - Humanization and epitope mapping of the H23 anti-MUC1 monoclonal antibody reveals
      a dual epitope specificity.
AB  - The tumor-associated antigen MUC1 is a cell surface mucin that is expressed on
      the apical surface of most glandular epithelial cells, including the ducts of the
      breast, ovary, pancrease, lung and colon. During malignancy, epithelial tissues
      regularly display elevated levels of MUC1 in a non-polar fashion and in an
      underglycosylated form, exposing cryptic peptide and carbohydrate epitopes. As
      such, MUC1 is regarded a potential target for immunotherapeutical intervention.
      Murine monoclonal H23 antibody specifically recognizes a MUC1 epitope on the
      surface of human breast cancer cells. We describe the cloning of the variable
      domains of H23 and their expression in (Escherichia coli) E. coli as maltose
      binding protein-scFv (MBP-scFv) fusions. We humanized H23 and evaluated the
      binding properties of the murine and the humanized recombinant forms, which were
      similar in affinity and specificity, but lower in apparent affinity in comparison
      to the original monoclonal IgG. We mapped the epitope of humanized H23 by
      affinity-selecting a phage-displayed random peptide library on humanized H23 scFv
      displaying bacteria. Our results show that humanized H23 binds an epitope
      corresponding to the MUC1 tandem repeat and an additional epitope not related to
      MUC1. These epitopes are competitive, bound with similar affinities and are
      recognized by the original murine H23 monoclonal antibody as well.

PMID- 15488945
TI  - Prominent dominant negative effect of a mutant Fas molecule lacking death domain
      on cell-mediated induction of apoptosis.
AB  - Using a panel of transfectant B lymphoma cells expressing varying amounts of the
      mutant Fas together with the endogenous wild type Fas, semi-quantitative studies
      on the dominant negative effect of a murine mutant Fas molecule lacking death
      domain were carried out. In anti-Fas antibody-mediated induction of apoptosis,
      the mutant molecules exerted significant dominant-negative effect only when their
      expression level was comparable to or higher than that of wild type molecules, or
      when exposed to low amounts of the antibody. The inhibitory effect was
      accompanied by the failure in DISC formation in spite of Fas aggregation. When
      they were subjected to T cell-mediated Fas-based induction of apoptosis, however,
      the dominant negative effect was prominent such that the expression of even a
      small amount of the mutant molecules resulted in significant inhibition. Such a
      strong inhibitory effect explains the dominant phenotype of this type of mutant
      Fas molecules in ALPS heterozygous patients and also implies that the
      physiological effectors for Fas in vivo are cells, i.e., FasL-expressing
      activated T cells.

PMID- 15488946
TI  - Antibodies against heat shock proteins and cholesterol in HIV infection.
AB  - This review summarizes data on the presence and function of different heat shock
      proteins (Hsp) in the HIV virions and the infected cells. A 60 kD heat shock
      protein-like molecule is present in the envelope of the human immunodeficiency
      virus type 1 which can specifically interact with the transmembrane glycoprotein
      gp41. The role of cholesterol in the so-called cholesterol-rich lipid raft where
      HIV is budding from the infected cells as well as the consequential insertion of
      cholesterol into the envelope of HIV virion are also discussed. Natural
      antibodies against 60 kD (Hsp60) and 70 kD (Hsp70) families of Hsp and
      cholesterol can be detected in most healthy individuals. HIV infection results in
      a sharp increase in the serum concentration of anti-Hsp70 and cholesterol
      antibodies whereas no difference in the concentration of anti-Hsp60 antibodies
      can be detected. Highly active antiretroviral therapy leads to normalization of
      the levels of both anti-Hsp70 and anti-cholesterol antibodies.

PMID- 15488948
TI  - Broader cross-reactivity after conjugation of V3 based multiple antigen peptides
      to HBsAg.
AB  - Vaccines against highly variable pathogens should elicite antibodies to a huge
      number of clinical isolates. For this purpose, new strategies to overcome the
      variability are needed. We have previously reported a useful method to conjugate
      multiple antigen peptides (MAPs) to carrier proteins. Also, we have suggested
      that these conjugates might enhance cross-reactivity in comparison to other
      synthetic structures. In this work, MAPs were synthesized and their respective
      conjugates to HBsAg were obtained. Two peptides from the V3 loop of HIV-1 were
      included in the MAPs as B cell epitopes because of their variability. Groups of
      mice were immunized and the immunogenicity and the level of cross-reaction to a
      panel of five heterologous V3 peptides were studied. Our results show that sera
      from mice immunized with MAPs coupled to HBsAg recognize a higher number of
      heterologous peptides (P < 0.05). This behavior was related neither to the
      immunogenicity nor the antigenicity of the synthetic structures. These results
      have important implications for the choice of better immunogens against variable
      epitopes.

PMID- 15488947
TI  - A novel inhibitor of the alternative complement pathway prevents antiphospholipid
      antibody-induced pregnancy loss in mice.
AB  - Studies in gene-targeted mice have demonstrated that factor B of the alternative
      complement pathway plays an important role in several disease models, but an
      exogenous inhibitor of factor B has not previously been available. We have
      developed an inhibitory monoclonal antibody directed against a critical epitope
      on mouse factor B and have tested it in a model of antiphospholipid (aPL)
      antibody (Ab)-induced fetal loss. Gene-targeted factor B-deficient mice (fB-/-)
      were injected with a fusion protein comprised of the second and third short
      consensus repeat (SCR) domains of mouse factor B linked to a mouse IgG1 Fc
      domain. Hybridomas were made from splenocytes of the immunized mouse. One mAb,
      designated 1379, produced an IgG1 antibody that inhibited alternative pathway
      activation in vitro and in vivo by preventing formation of the C3bBb complex.
      Strikingly, this mAb inhibited alternative pathway activation in serum from mice,
      rats, humans, monkeys, pigs and horses. Fab fragments made from this mAb also
      inhibited alternative pathway activation. Epitope mapping demonstrated that this
      antibody binds to factor B within the third SCR domain. When mAb 1379 was
      administered to mice that also received human IgG containing antiphospholipid
      antibodies, it provided significant protection from antiphospholipid antibody
      induced complement activation and fetal loss. Thus, this mAb to factor B has
      broad species reactivity and effectively inhibits alternative pathway activation.
      The mAb protects mice in an in vivo model of antiphospholipid antibody syndrome,
      demonstrating the therapeutic potential for the inhibition of factor B in this
      disease.

PMID- 15488949
TI  - C5 complement deficiency in a Spanish family. Molecular characterization of the
      double mutation responsible for the defect.
AB  - The complement C5 deficiency is a recessive autosomal defect associated with
      recurrent infectious episodes, generally caused by Gram-negative micro-organisms.
      To date, only two mutations responsible for C5 deficiency have been
      characterized, both in heterozygosis. In this paper, we evaluate by
      immunochemical methods the C5 deficiency in a six-member family, in which one
      member suffered from meningococcal sepsis and several pneumonia episodes; and a
      second one with two bacterial meningitis episodes and frequent tonsillitis,
      pneumonia and herpetic episodes. We also characterize the molecular basis of this
      deficiency. No C5 protein was found in the serum from three of the children. They
      were found to be homozygous for a double mutation in the exon 40 of the C5 gene.
      The parents and the other children have half-normal levels of C5, and they were
      heterozygotes for the double mutation. This mutation modifies the reading frame,
      leading to a premature stop codon, and the resulting protein lacks 50 amino
      acids. As a result, homozygotes and heterozygotes have a total or a partial C5
      deficiency respectively. This is the first report of a whole molecular
      characterization of C5 deficiency.

PMID- 15488950
TI  - Analysis and characterization of the expression of the secretory and membrane
      forms of IgM heavy chains in the pufferfish, Takifugu rubripes.
AB  - We investigated the structure and expression of immunoglobulin genes in the
      pufferfish, Takifugu rubripes, a highly prized and economically important fish
      species. The cDNA fragment that partially encodes the constant region of the IgM
      heavy chain was isolated in these animals by RACE using degenerate primers after
      which it was used as a probe for screening IgM heavy chains in a fugu splenic
      cDNA library. The structural feature of the constant region of fugu sIgM was
      found to consist of four constant domains (CH1 to CH4), while mIgM was shown to
      contain a deletion of the CH4 domain, and its transmembrane domain was directly
      spliced to the CH3 domain as found in other teleosts. This feature may be common
      to all teleosts. In addition, five VH genes isolated in this study fell into two
      families based on their variability. Analysis of genomic sequences from the fugu
      genomic database also showed that there are only two VH families in the genome.
      The IgM gene was preferentially expressed in presumptive lymphoid tissues.
      Moreover, in situ hybridization revealed that large numbers of IgM positive cells
      were widely distributed throughout the spleen, head kidney, kidney, and thymus,
      confirming that these tissues were major sites of antibody production in fish.
      The expressions of IgM in the mucosal organs such as the skin, gills, and
      intestine suggest that they, too, contribute to humoral immunity in aquatic
      animals. The expression of IgM mRNA in the early development stages of this fish
      suggests that its larval form possesses a protective defense mechanism against
      foreign invaders.

PMID- 15488951
TI  - Molecular characterization of a panel of murine monoclonal antibodies specific
      for the SARS-coronavirus.
AB  - The availability of monoclonal antibodies (mAbs) specific for the SARS
      coronavirus (SARS-CoV) is important for the development of both diagnostic tools
      and treatment of infection. A molecular characterization of nine monoclonal
      antibodies raised in immune mice, using highly purified, inactivated SARS-CoV as
      the inoculating antigen, is presented in this report. These antibodies are
      specific for numerous viral protein targets, and six of them are able to
      effectively neutralize SARS-CoV in vitro, including one with a neutralizing titre
      of 0.075 nM. A phylogenetic analysis of the heavy and light chain sequences
      reveals that the mAbs share considerable homology. The majority of the heavy
      chains belong to a single Ig germline V-gene family, while considerably more
      sequence variation is evident in the light chain sequences. These analyses
      demonstrate that neutralization ability can be correlated with specific murine
      V(H)-gene alleles. For instance, one evident trend is high sequence conservation
      in the V(H) chains of the neutralizing mAbs, particularly in CDR-1 and CDR-2. The
      results suggest that optimization of murine mAbs for neutralization of SARS-CoV
      infection will likely be possible, and will aid in the development of diagnostic
      tools and passive treatments for SARS-CoV infection.

PMID- 15488952
TI  - Cytoplasmic domains of the transporter associated with antigen processing and P
      glycoprotein interact with subunits of the proteasome.
AB  - The proteasome is a multi-protein complex that degrades cellular proteins as well
      as foreign proteins destined for antigen presentation. The latter function
      involves the immunoproteasome, in which several proteasome subunits are exchanged
      for gamma-interferon-induced subunits. The transporter associated with antigen
      processing (TAP) transports proteasome-generated peptides across the membrane of
      the endoplasmic reticulum (ER) prior to presentation on the plasma membrane. We
      demonstrate interactions between the cytoplasmic domains of TAP subunits and
      subunits of both the proteasome and the immunoproteasome, suggesting direct
      targeting of antigenic peptides to the ER via a TAP-proteasome association. We
      also show interaction between one of the cytoplasmic domains of P-glycoprotein
      and a proteasome subunit, but not the corresponding immunoproteasome subunit,
      suggesting a possible role for P-glycoprotein in the transport of proteasome
      derived peptides.

PMID- 15488953
TI  - Multiple assessments of depressive symptoms as an index of depression in
      population-based samples.
AB  - The incremental validity of repeated measurements of a short depression
      questionnaire was examined regarding the clinical diagnosis of depression.
      Participants were 951 randomly selected women of around menopausal age. They
      completed the Edinburgh Depression Scale (EDS) at two time points, with
      approximately 18 months in between. At the second time point, they participated
      in a structured clinical interview for depression diagnosis based on the Research
      Diagnostic Criteria (RDC). With repeated assessments, specificity and negative
      predictive value (NPV) did not change much relative to a single assessment, with
      a specificity of 95.0% and a NPV of 91.7% at a cut-off score of 12 on the EDS. As
      expected, sensitivity dropped, from 87.9% to 58.8%. However, positive predictive
      value (PPV) increased from 42.0% to 49.1% at a cut-off of 12. When using a cut
      off score of 15 on the EDS, the PPV based on both EDS measurements reached 61.8%,
      yielding a 25-fold probability of being a case for women scoring above 15 at both
      time points (OR=24.54, 95% CI=14.24-42.28). In conclusion, the 10-item EDS is a
      reliable, valid and valuable screening instrument. When employed repeatedly, a
      more stable depression may be tapped, which can be of substantial value for both
      epidemiological research and clinical practice.

PMID- 15488954
TI  - Elevated salivary dehydroepiandrosterone-sulfate but normal cortisol levels in
      medicated depressed patients: preliminary findings.
AB  - Major depression is often associated with dysregulation of the hypothalamic
      pituitary-adrenal (HPA) axis. In contrast to cortisol, dehydroepiandrosterone
      sulfate (DHEA-S) has been less extensively studied in depressed patients. This
      study examined salivary morning and evening levels of cortisol and DHEA-S in 13
      medicated, unipolar, non-psychotic depressed patients and 13 healthy volunteers.
      Diurnal declines in cortisol and DHEA-S levels were found in both depressed and
      control groups. In patients compared with controls, DHEA-S was significantly
      elevated, in conjunction with normal cortisol levels. Based on DHEA-S at 22:00 h
      only, 77% of the subjects were correctly classified in a discriminant analysis as
      depressed or control. When simultaneously entered in a multiple regression
      analysis, DHEA-S (morning and evening) and cortisol (evening only) predicted
      symptom severity in depressed patients. These preliminary results suggest that
      DHEA-S may be a more sensitive indicator of depression and symptom severity than
      cortisol in medicated but still clinically depressed patients.

PMID- 15488955
TI  - Depression biases the recognition of emotionally neutral faces.
AB  - Functional abnormalities in emotion-related brain systems have been implicated in
      depression, and depressed patients may therefore attribute emotional valence to
      stimuli that are normally interpreted as emotionally neutral. The present study
      examined this hypothesis by comparing recognition of different facial expressions
      in patients with moderate to severe depression. Eighteen depressed patients and
      18 matched healthy controls made a forced-choice response to briefly presented
      neutral, happy, and sad faces. Recognition accuracy and response time were
      measured. Twelve patients were retested after showing signs of symptom remission.
      Depressed patients and controls were equally accurate at recognizing happy and
      sad faces. Controls also recognized neutral faces as accurately as happy and sad
      faces, but depressed patients recognized neutral faces less accurately than
      either happy or sad faces. Depressed patients were also particularly slow to
      recognize neutral faces. The impairment in processing of neutral faces was still
      evident after symptom remission. Error analyses showed that depressed patients
      attributed not only sadness, but also happiness (in remission), to neutral faces.
      These results suggest that, unlike healthy subjects, depression-prone individuals
      do not seem to perceive neutral faces as unambiguous signals of emotional
      neutrality.

PMID- 15488956
TI  - Differential impairments of facial affect recognition in schizophrenia subtypes
      and major depression.
AB  - The goal of this study was to assess facial affect recognition abilities in
      subjects with various schizophrenia subtypes and subjects with major depression.
      A total of six disorganized, 21 paranoid and 18 residual subjects with
      schizophrenia (DSM-IV criteria) were compared with 21 subjects with major
      depression (DSM-IV criteria) and 30 matched healthy control subjects. Two
      experimental tasks requiring the sorting and rating of emotional facial
      expressions were applied. Disorganized and paranoid subjects showed strong
      impairments in the sorting of emotional facial expressions. Depressive subjects
      displayed only minor deficits, and residual subjects were unimpaired. Subjects
      with disorganized schizophrenia rated emotional facial expressions as more
      aroused, and depressive subjects rated them as less aroused, than the other study
      groups. Our study demonstrates strong deficits in facial affect recognition in
      subjects with schizophrenia and pronounced disorganized or psychotic symptoms.
      Deficits in facial affect recognition are specific to schizophrenia. They may be
      considered as a state marker of schizophrenia.

PMID- 15488957
TI  - Brief emotion training improves recognition of facial emotions in chronic
      schizophrenia. A pilot study.
AB  - Impaired emotional communication may be an important contributing factor to poor
      social function in schizophrenia. This pilot study examined the effect of emotion
      training exercises on the perception of facial emotional expression. Twenty male
      chronic schizophrenia patients underwent three training sessions using a
      computerized Emotion Training program, developed for teaching autistic children,
      which was adapted to the clinical setting. Patients were assessed before and
      after training with validated tests of identification of facial emotions (PEAT,
      ER40), differentiation of facial emotions (EmDiff) and working memory. In
      comparison to baseline, patients performed significantly better on the PEAT and
      ER40 tests after training. No change was observed in EmDiff or in cognitive test
      performance. Brief Emotion Training can improve recognition of facial emotional
      expressions in chronic schizophrenia patients. This may be due to increased
      patient awareness of emotional aspects of stimuli and/or improvement in specific
      emotional perceptual skills. Further studies of Emotion Training as a potential
      treatment modality are warranted.

PMID- 15488958
TI  - Does social cognition influence the relation between neurocognitive deficits and
      vocational functioning in schizophrenia?
AB  - Research on barriers to treatment and rehabilitation readiness in people with
      schizophrenia, especially focusing on risk factors of poor outcome in social and
      vocational functioning, has focused on the role of social cognition and
      neurocognition. Others have hypothesized that social cognition (i.e., encoding
      and understanding of social cues guided by social schemas or scripts) may be one
      mediator between basic neurocognition and functional outcome. Our study analyzes
      data from 133 DSM-IV schizophrenic inpatients on a rehabilitation ward using
      structural equation modeling (SEM) to test whether social cognition has a
      stronger and more direct influence on vocational functioning than nonsocial
      cognition. The results supported the hypothesized model; that is, 25% of work
      related social skills could be explained by social cognition and nonsocial
      cognition. The direct impact of nonsocial cognition on vocational functioning was
      smaller than the impact of social cognition on work-related social skills.
      Nevertheless, an overwhelming proportion of social cognition (83%) could be
      explained by nonsocial cognition.

PMID- 15488959
TI  - Dichotic listening in schizophrenic patients: effects of previous vs. ongoing
      auditory hallucinations.
AB  - Auditory hallucinations (AH) in schizophrenia have been found to be related to
      both functional and structural brain abnormalities of left temporal lobe language
      areas. We do not know if these rain abnormalities are state or trait markers for
      AH. This study tested these alternatives by contrasting schizophrenic patients
      with ongoing AH and with a previous history of AH. A heterogeneous group of 26
      schizophrenic patients was compared with a healthy control group matched for
      education and age. We used a verbal dichotic listening (DL) test with consonant
      vowel syllables to study hemispheric asymmetry and the functional integrity of
      the left temporal lobe language areas. All subjects were tested during a divided
      and two focused attention conditions. Our data suggest that abnormal DL asymmetry
      for language stimuli is a state marker for AH, seen during the perception of AH.
      In contrast, problems of modulating DL performance by means of attentional
      control are a trait marker, seen both in patients with ongoing AH and only a
      history of AH.

PMID- 15488960
TI  - Early- versus late-onset obsessive-compulsive disorder: investigating genetic and
      clinical correlates.
AB  - There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated
      by genetic factors. Although the precise mechanism of inheritance is unclear,
      recent evidence has pointed towards the involvement of the serotonergic and
      dopaminergic systems in the disorder's development. Furthermore, early-onset OCD
      appears to be a subtype that exhibits distinct clinical features and that is
      associated with greater familial loading. In the present investigation, South
      African OCD patients (n=252) were stratified according to age of onset and were
      clinically assessed. Additionally, selected variants in genes encoding
      serotonergic and dopaminergic components were investigated in a Caucasian OCD
      subset (n=180). This subgroup was further stratified to evaluate the role that
      these candidate genes may play in the genetically homogeneous Afrikaner subset
      (n=80). Analysis of the clinical data revealed an association between early age
      of onset and an increased frequency of tics, Tourette's disorder, and
      trichotillomania (TTM). The genetic studies yielded statistically significant
      results when the allelic distributions of genetic variants in the dopamine
      receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data
      support a role for the dopaminergic system, which may be relevant to the
      development of early-onset OCD.

PMID- 15488961
TI  - Changes in lymphocyte subsets after short-term pharmacotherapy in patients with
      panic disorder.
AB  - Panic disorder is associated with a high frequency of comorbid immunological
      diseases, such as allergies and asthma, although the psychoneuroimmunology of
      panic disorder is relatively unexplored. The objective of this study was to
      determine whether panic patients have different immunological findings compared
      with normal healthy subjects and whether changes in immune function are
      associated with short-term pharmacotherapy. We also examined whether
      immunological variables were associated with clinical severity and serum
      catecholamine levels. Patients with panic disorder (n=26) and healthy control
      subjects (n=26) were recruited for this study. All patients were treated with
      paroxetine for 3 months. We measured the lymphocyte subsets, psychopathological
      characteristics and serum catecholamine (norepinephrine and epinephrine) levels.
      Panic patients did not differ initially from control subjects in peripheral
      lymphocyte phenotypic markers. After drug therapy, however, percentages of
      circulating CD3+, CD4+ and CD8+ T lymphocytes were significantly increased, while
      the percentage of CD19+ B lymphocytes was significantly decreased in the
      patients. The difference in the percentage of CD8+ T lymphocytes before and after
      treatment was negatively correlated with pretreatment Global Clinical Impression
      scores. The lymphocyte subsets were not significantly associated with serum
      catecholamine levels in panic patients. In conclusion, panic patients showed
      increased CD3+, CD4+ and CD8+ T lymphocyte proportions and a decreased B
      lymphocyte proportion after 3 months of drug therapy. This finding suggests that
      pharmacological treatment may affect immune function in panic patients.

PMID- 15488962
TI  - A help-line for children. Seasonal variations in issues.
AB  - The objectives of the study were to describe monthly variations in issues in
      calls to a help-line for children and adolescents. All 80,983 calls to a Red
      Cross Help-Line for children in 1991-1997 were included. In 22,698 calls,
      information about age, sex or issue could be identified. A monthly variation in
      frequency of calls with peaks in April and November and a correlation with the
      absolute values of monthly changes in length of day were found. Conversations
      concerning psychiatric suffering were more frequent in January or February and
      less frequent than expected in May/June and December. Conversations about
      sexuality correlated with the frequencies of births in the adult population 9
      months later. A spring and fall peak in total calling and a winter peak in calls
      for depression, anxiety, pain and neglect were described.

PMID- 15488963
TI  - Repetitive transcranial magnetic stimulation as an add-on therapy in the
      treatment of mania: a case series of eight patients.
AB  - The aim of this study is to assess the efficacy of repetitive transcranial
      magnetic stimulation (rTMS) as an add-on therapy in the treatment of manic
      bipolar patients. Eight patients were enrolled in an open trial. They received
      fast rTMS (five trains of 15 s, 80% of the motor threshold, 10 Hz) over the right
      dorsolateral prefrontal cortex (DLPFC). They were evaluated using the Mania
      Assessment Scale (MAS) and the Clinical Global Impression (CGI) at baseline and
      at day 14. All patients were taking medication during the treatment trial. There
      was a significant improvement of manic symptoms at the end of the trial. No side
      effects were reported. The results show a significant improvement of mania when
      patients are treated with fast rTMS over the right DLPFC. However, these results
      have to be interpreted with caution since they derive from an open case series
      and all the subjects were taking psychotropic medication during rTMS treatment.
      Double-blind controlled studies with a sham comparison condition should be
      conducted to investigate the efficiency of this treatment in manic bipolar
      disorders.

PMID- 15488964
TI  - Efficacy of open-label venlafaxine in subjects with major depressive disorder:
      associations with neuroendocrine response to serotonergic and noradrenergic
      probes.
AB  - An open-label pilot study explored the relationship between severity of
      depressive symptoms and venlafaxine dose required for clinical efficacy in
      outpatients with major depressive disorder (MDD). The utility of the
      neuroendocrine response to serotonergic (ipsapirone) and noradrenergic
      (clonidine) probes as predictors of venlafaxine dosage required for effective
      treatment was also explored. Nineteen medically healthy medication-free
      outpatients over 18 years of age who met criteria for MDD were studied.
      Participants received either a 20-mg dose of ipsapirone orally, a 0.002-mg/kg
      intravenous dose of clonidine, or placebo. Following a 1-week single-blind
      placebo lead-in, all subjects were treated with immediate release venlafaxine.
      Low-dose responders were defined as those subjects experiencing a >50% decrease
      in depression score on 37.5 mg, b.i.d., and high-dose responders were defined as
      those subjects experiencing similar improvement on venlafaxine doses of 75 mg,
      b.i.d., or higher. Subjects responding to low-dose treatment had a lower mean
      baseline Hamilton depression score than subjects requiring high-dose treatment.
      Neuroendocrine and temperature responses to clonidine or ipsapirone challenges
      were not significantly different in the high- vs. low-dose responders. Evaluation
      of models of "serotonergic-responsive" and norepinephrine-responsive" depression
      requires larger numbers of patients.

PMID- 15488965
TI  - Day stay pediatric tonsillectomy--a safe procedure.
AB  - OBJECTIVE: There is a controversy about day stay pediatric tonsillectomy in the
      UK and Australia. New Zealand has a similar health structure and we wished to
      compare day stay tonsillectomy from our hospital with those reported from other
      centers. METHODS: We performed a prospective audit of day stay tonsillectomy to
      determine conversion to hospital admission rate and the incidence of
      postoperative hemorrhage. RESULTS: There were 4850 paediatric tonsillectomies
      performed with 80% of them as day stay procedures over a 9-year study period
      (1993-2002) in a university-affiliated tertiary children's hospital. The primary
      postoperative hemorrhage rate (within 24h of surgery) was 0.9% (CI 0.68-1.22%)
      and 83% occurred within the mandatory 4h postoperative observation period.
      Primary hemorrhage requiring re-operation to achieve hemostasis occurred in 18
      children (0.37%, CI 0.2-0.54%). No child with a primary hemorrhage who presented
      after discharge following day stay surgery required re-operation or blood
      transfusion. Day stay surgery was planned in 4041 children and 4.7% (CI 4.1-5.4%)
      required conversion to hospital admission. Postoperative vomiting was the most
      common indication for conversion (2.65%, CI 2.2-3.1%), while hemorrhage
      contributed only 0.95% (CI 0.64-1.24%). CONCLUSIONS: This study was performed in
      a health system similar to that of Australia and the UK. Complication and
      conversion rates are similar to those reported in North American centers.
      Pediatric day stay tonsillectomy is a safe procedure when performed with strict
      preoperative criteria, trained day stay unit (DSU) staff, and with in-patient
      facilities on site.

PMID- 15488966
TI  - Outcome of adenotonsillectomy for severe obstructive sleep apnea in children.
AB  - OBJECTIVE: To study changes in sleep behavior and quality of life in children
      after adenotonsillectomy for severe obstructive sleep apnea identified by a
      respiratory distress index > or = 30. METHODS: Children enrolled in the study
      underwent adenotonsillectomy and had both pre- and post-operative
      polysomnography. Caregivers also completed an OSA-18 quality of life survey prior
      to polysomnography and within 6 months of surgery. Paired Student's t-tests were
      used to compare pre- and post-operative scores. RESULTS: The study population
      included 29 children. The mean age was 7.1 years (range 1.4-17.0). The most
      common comorbidities were obesity, asthma and allergic disease. The mean pre
      operative RDI was 63.9 and the mean post-operative RDI was 14.2 (P < .0001). The
      mean total OSA-18 score before surgery was 77.6 and after surgery was 33.2. The
      differences in pre- and post-operative OSA-18 total scores and domain scores were
      significant (P < .0001). CONCLUSION: Children with severe OSA who undergo
      adenotonsillectomy show a significant improvement in RDI and in quality of life
      over a period of several months after surgery. However, OSA does not resolve in
      the majority of these children and post-operative PSG is recommended to identify
      those who may require additional therapy.

PMID- 15488967
TI  - Investigation of antioxidant status in children with acute otitis media and
      tonsillitis.
AB  - OBJECTIVE: Antioxidant enzymes status was investigated in children with acute
      otitis media (AOM) and acute tonsillitis. The aim was to determine the effect of
      oxidative damage due to free radicals on the antioxidant enzymes status in
      children with AOM and acute tonsillitis. METHODS: We measured erythrocyte levels
      of superoxide dismutase and glutathione peroxidase (GPx) and activity of serum
      catalase, ceruloplasmin, albumin and total bilirubin in 23 children with AOM, 27
      with acute tonsillitis and 17 control subjects. RESULTS: There was statistically
      significant difference between the groups for all parameters. All antioxidant
      activities except for albumin level were increased in the studies groups. When
      the values of AOM and acute tonsillitis were compared, there was statistically
      significant difference between the groups for erythrocyte GPx. CONCLUSION: Our
      findings indicate that not only a few antioxidant enzymes but almost all
      antioxidant activities showed a significant enhancement in children with AOM and
      acute tonsillitis.

PMID- 15488968
TI  - Percutaneous tracheotomy in children.
AB  - We present three cases of the Fantoni percutaneous translaryngeal tracheostomy
      (TLT) performed under direct rigid bronchoscopy. The surgeries were performed in
      the near-drowned 5-year-old boy, and 15-year-old lupus erythematosus girl with a
      permanent brain damage resulted from a cardiac arrest, 11-year-old cardiac girl
      with postintubation laryngeal stenosis. In the first two cases, the procedure
      went uneventful; in one case the tube was accidentally pulled out during the
      rotation phase and surgical tracheostomy was performed. We describe the TLT
      procedure in details, calling special attention at the fact that the TLT is
      especially suitable for children below 10 years of age and is associated with
      very few complications.

PMID- 15488969
TI  - Efficacy of bupivacaine for post-tonsillectomy pain: a study with the intra
      individual design.
AB  - OBJECTIVE: To determine the effectiveness of postoperative local anesthesia in
      tonsillectomy patients using an intra-individual study design. METHODS: Thirty
      patients aged 5-15 were included in a prospective study. Patients received a
      local infiltration of 0.5% bupivacaine solution on the right tonsillar bed, and
      received a local infiltration of normal saline on the left tonsillar bed.
      Patients were asked to localize pain in terms of most disturbing side of the
      pharynx, on the 1st, 4th, 8th, 16th, 24th hours. RESULTS: Regarding pain over a
      24-h period, there was a significant difference between two sides, after the 8th
      hour. CONCLUSION: Postoperative local bupivacaine infiltration in tonsillectomy
      patients was effective in children.

PMID- 15488970
TI  - Guidelines and recommendations for testing of Cx26 mutations and interpretation
      of results.

PMID- 15488971
TI  - Syndromic etiology in children at schools for the deaf in Turkey.
AB  - OBJECTIVE: The aim of this study was to determine the syndromic etiology of
      bilateral severe sensorineural hearing disorders in children and current
      etiological causes to reduce the cases in the unknown group. METHODS: This study
      was conducted on 550 students of five schools for the deaf in Istanbul and
      Zonguldak, Turkey. Otologic, audiologic, dysmorphologic, ophthalmologic and
      dental examinations were performed in all children. Familial and medical
      histories were obtained. RESULTS: The etiology of hearing loss was genetic in 346
      (62.90%), acquired in 107 (19.45%) and unknown in 97 (%17.63) cases. A total of
      619 malformations were defined in 550 children and 99 of them belonged to a
      syndrome. We identified 33 different syndromes for these 99 syndromic children.
      Syndromic etiology was found in 18.0% of the total and 28.61% of the subjects
      with genetic etiology. Most common syndrome was Waardenburg syndrome which
      occurred in 33 children. CONCLUSION: The incidence of hereditary hearing
      impairment is very high in developing countries compared to developed countries.
      Prevention is essential to reduce the incidence, multidisciplinary approach and
      genetic counselling are necessary in this regard.

PMID- 15488972
TI  - Nasal obstruction and headache. A real correlation?
AB  - OBJECTIVE: to evaluate the relationships between headache and nasal obstruction
      or nasal allergy on a group of Italian school children. METHODS: One hundred
      twenty-six children suffering from headache, were enrolled in the study. All
      patients underwent an accurate clinical history, a complete ENT objective
      examination, an Anterior Active Rhinomanometry, an analysis of nasal mucociliary
      transport time and a skin test on the inner forearm. RESULTS: Nasal resistances
      were increased in 101 out of 105 of children (96.2%) affected by severe headache
      (group A) and in 5 out of 21 (23.8%) of those affected by sporadic headache (P <
      0.0001), for an odds ratio of 80.0 (95% CI, 19-343). The analysis of mucociliary
      transport time offered results comparable with those of the Anterior Active
      Rhinomanometry. CONCLUSIONS: Dysfunctions of nasal physiology, as stated by the
      alteration of nasal resistances and nasal mucociliary transport, seem to be able
      to affect the development and the characteristics of headaches; specifically we
      found that children with an altered nasal physiology have more severe and more
      frequent attacks of headache.

PMID- 15488973
TI  - Sensorineural hearing loss in Nigerian children with sickle cell disease.
AB  - AIM: To study the prevalence and pattern of sensorineural hearing loss (SNHL) in
      Nigerian children with sickle cell disease (SCD). MATERIALS: Fifty-two children
      with SCD were assessed. Otologic examination and audiometric tests were
      performed. There were 36 males and 16 females. Their age ranged from 6 to 19
      years. RESULT: Seven children had hearing impairment. After hemoglobin
      categorization, all the SCD patients were found to belong to the homozygous
      (HbSS) group. There were no HbSC nor other variants detected. Prevalence of SNHL
      was 13.4% in these patients but the general population prevalence rate found in a
      control group was 6.2%. CONCLUSION: SCD has many organ manifestations and
      complication among which is sensorineural hearing loss. Regular audiologic
      assessment, counselling and rehabilitation of these patients with hearing aids
      are recommended.

PMID- 15488974
TI  - Management of nasal septal abscess in childhood: our experience.
AB  - A nasal septal abscess is usually the result of an infected hematoma of the
      septum. A secondary septal abscess may be the result of infections extending from
      any of the neighbouring tissues. The necrosis of septal cartilage may lead to
      nasal deformities and severe impairment of nasal patency and growth. OBJECTIVES:
      Assess if the drainage of the abscess and the immediate reconstruction of the
      destroyed nasal septum in the acute phase is the best treatment to prevent short-
      and long-term effect on nasal and midface growth. METHODS: Three pediatric
      patients treated with drainage and immediate implantation of homologous bank
      cartilage prior to 1990 and four treated with mosaic plastic using small pieces
      of residual septal cartilage assembled with fibrin glue. RESULT: No complication
      were observed in the follow-up and any deformities in the long-term controls.
      CONCLUSIONS: The drainage and immediate reconstruction of the nasal septum are
      the golden standard in the treatment of the septum infected haematoma.

PMID- 15488975
TI  - Endoscopic KTP laser excision of severe tracheotomy-associated suprastomal
      collapse.
AB  - OBJECTIVE: The purpose of this study was to investigate the feasibility, safety,
      and clinical utility of potassium-titanium-phosphate (KTP) laser bronchoscopy for
      excision of severe, obstructing tracheotomy-associated suprastomal collapse.
      METHODS: A retrospective review was performed of six children at a tertiary care
      children's hospital with severe tracheotomy-associated collapse of the
      suprastomal anterior tracheal wall cartilage, precluding decannulation. All
      subjects had undergone KTP laser endoscopic excision of the collapsed segment of
      suprastomal tracheal cartilage. Medical records were assessed for: (1) endoscopic
      demonstration of relief of suprastomal collapse, and (2) successful tracheotomy
      decannulation. RESULTS: All six patients had endoscopic evidence of relief of
      suprastomal airway obstruction after KTP laser therapy. Five of six (83%)
      subsequently underwent successful decannulation. There was one case of minimal
      thermal airway injury associated with a laser fire during use of the KTP laser,
      the effects of which were fortunately transient. CONCLUSIONS: KTP laser
      bronchoscopic excision of severe tracheotomy-associated suprastomal collapse: (1)
      is a feasible technique; (2) results in relief of suprastomal obstruction with
      subsequent successful decannulation in selected patients; and (3) avoids the need
      for more extensive open neck procedures. However, risks of KTP laser therapy are
      not negligible and strategies must be in place to minimize the occurrence of
      complications.

PMID- 15488976
TI  - Assessing the outcome of surgery to correct velopharyngeal insufficiency with the
      pediatric voice outcomes survey.
AB  - OBJECTIVE: To assess the functional outcome of surgery for velopharyngeal
      insufficiency (VPI) by administering the pediatric voice outcomes survey (PVOS)
      to the parents of the affected children. DESIGN: Prospective longitudinal study.
      SETTING: Tertiary referral pediatric otolaryngology office. SUBJECTS: Twelve
      children who underwent surgery to correct VPI during the 12-month-period between
      1 January 2002 and 31 December 2002. METHODS: Parents of the 12 children were
      administered the PVOS prior to surgery and again 6 weeks post-operatively. The
      PVOS is a validated instrument designed to measure voice-related quality of life
      (V-RQOL). The score has been transformed to range from 0 (low V-RQOL) to 100
      (high V-RQOL). RESULTS: The mean age of the children was 5 years (standard
      deviation [S.D.], 2.3 years). Seven children underwent sphincteroplasty and five
      had a superior based pharyngeal flap as a primary procedure. Three children
      required secondary procedures to correct their underlying VPI and one of those
      had a third procedure consisting of a posterior wall fat injection. The mean pre
      operative PVOS score was 38.3 (S.D., 12) and the mean 6 weeks post-operative
      score was 72.3 (S.D., 22.7) (paired t-test; P < 0.001). CONCLUSION: The PVOS
      represents a valid clinical tool to measure the functional impact of surgery to
      correct pediatric velopharyngeal insufficiency.

PMID- 15488977
TI  - Acute mastoiditis in infancy: the Soroka experience: 1990-2000.
AB  - Acute mastoiditis (AM) is an uncommon but serious complication of acute otitis
      media (AOM). In the pre-antibiotic era, AM was seen more frequently than it is
      today, but it was rare in infants. However, in the last two decades an increase
      in the incidence of AM in infancy has been reported in the literature. During the
      years 1990-2002, we treated 113 patients with 128 episodes of AM; of them, 24
      were infants (median age 6 months; 18 males) who suffered from 26 episodes of AM.
      Twenty developed AM as a complication of their first episode of AOM. One of the
      four infants with a prior history of AOM suffered from common variable
      immunodeficiency. A significant increase in the incidence of AM in infants was
      recorded during the study period (P = 0.01). The most common presenting clinical
      signs were post-auricular swelling and fever >38 degrees C (77% and 77%,
      respectively, of all patients). Seventeen episodes of AM were not treated with
      prior antibiotics. Tympanocentesis was performed in all episodes of AM. Middle
      ear fluid culture was positive in 17 (65%) of the 26 AM episodes. The most common
      pathogens cultured were Streptococcus pneumoniae (10 infants, 58% of all
      pathogens, 3/10 intermediately susceptible to penicillin) followed by
      Streptococcus pyogenes (4, 23%), non-typable H. influenzae (2, 12%) and S. aureus
      (1, 6%). Temporal bone CT showed bone destruction in 14 patients; 3 infants had
      subperiosteal abscesses and 3 lateral sinus thrombosis. Ten infants underwent
      mastoid surgery due to non-resolution of symptoms and signs with antibiotic
      therapy. Eight underwent cortical mastoidectomy with two patients undergoing
      ventilation tube introduction only. The remainder of the infants healed with
      conservative treatment. CONCLUSIONS: (1) A significant increase in the incidence
      of AM in infants was recorded over the last decade, though a specific reason for
      this trend remains uncertain; (2) Most of the cases of AM followed the infant's
      initial AOM episode, and most of the infants had not received prior antibiotic
      therapy; (3) The clinical signs and symptoms of AM were more severe in infants
      than in older patients; (4) While S. pneumonia was the most common pathogen
      isolated in middle ear fluid cultures, the involvement of S. pyogenes in AM was
      higher than that reported in AOM.

PMID- 15488978
TI  - Chondroma of the bony external auditory canal attached to the short process of
      the malleus.
AB  - A chondroma located in the external auditory canal is a rare finding. Here, we
      report the case of a 12-year-old girl who attended our clinic with complaints of
      a rustling sound in her left ear. Otoscopic examination revealed a tiny bone-like
      tumor protruding from the anterior wall of the bony external auditory canal,
      attached to the short process of the malleus. An audiogram revealed a conductive
      hearing loss in her left ear, although she did not notice it. After excision of
      the tumor through the ear canal, her complaints disappeared and her hearing
      recovered. Histologically, the tumor proved to be a chondroma.

PMID- 15488979
TI  - Otolaryngologic manifestations of PHACE syndrome.
AB  - Two case reports of PHACE syndrome (posterior fossa malformations (P),
      hemangiomas (H), arterial anomalies (A), coarctation of the aorta and cardiac
      defects (C), and eye abnormalities (E)) are presented. Clinical characteristics
      consisted of cutaneous and airway hemangiomas, aortic coarctation, and left
      superior vena cava in one child and cutaneous and airway hemangiomas, sternal
      clefting, and supraumbilical raphe in the other child. Treatment modalities
      included systemic and intralesional steroids for cutaneous and airway
      hemangiomas, submucosal resection and laryngotracheal reconstruction for airway
      hemangiomas, repair of aortic coarctation, and laser treatment of cutaneous
      hemangiomas. PHACE syndrome poses a significant potential for airway compromise
      from hemangiomas, which may require multimodality treatment.

PMID- 15488980
TI  - A unique presentation of a pharyngeal auricle.
AB  - Congenital lesions typically present in early childhood. Based on their location
      and presentation, the diagnosis and treatment is usually obvious. Because of the
      complexities and uniqueness of head and neck embryology, rare congenital lesions
      develop and this should be of interest to the otolaryngologist. In this report we
      present a rare case of a pharyngeal auricle that manifested itself as a polyp
      within the oropharynx of an infant.

PMID- 15488981
TI  - Vestibular neuritis in a child with otitis media with effusion; clinical
      application of vestibular evoked myogenic potential by bone-conducted sound.
AB  - Vestibular evoked myogenic potential (VEMP) has been applied for patients with
      vestibulo-cochlear disorders. The impairment of the sound transmission due to
      middle ear pathology affects VEMP results. In children, otitis media with
      effusion (OME) is well documented and it is difficult to apply conventional VEMP
      in such cases. To overcome the attenuation of stimulation due to middle ear
      pathology, VEMP by bone-conducted sound has been developed. We report a 3-year
      old girl with vestibular neuritis and OME as a representative case of clinical
      application of VEMP by bone-conducted sound. VEMP by bone-conducted sound can be
      an alternative method to elicit vestibular-dependent potential.

PMID- 15488982
TI  - Failure to thrive caused by the coexistence of vallecular cyst, laryngomalacia
      and gastroesophageal reflux in an infant.
AB  - Vallecular cyst is a rare but dangerous cause of stridor in neonates and young
      infants. Without recognition and proper therapy, the resulting airway obstruction
      can lead to serious morbidity and mortality. We herein report a young infant with
      a vallecular cyst synchronous with laryngomalacia and gastroesophageal reflux.
      The infant initially presented with signs and symptoms mimicking more benign
      laryngomalacia. Diagnosis was delayed with accompanying failure to thrive. The
      cyst was revealed by a barium esophagogram and confirmed by flexible
      bronchoscopy. Laryngomicrosurgery with CO(2) laser not only removed the cyst, but
      resolved the co-existing laryngomalacia and gastroesophageal reflux as well.
      After surgery, the infant was symptom free and exhibited a steady weight gain.
      There was no recurrence during 1 year of follow-up. We have reviewed the
      literature for this rare and potentially devastating lesion.

PMID- 15488983
TI  - Giant malignant peripheral nerve sheath tumor of the neck in a patient with
      neurofibromatosis-1.
AB  - Sixteen-year-old mentally retarded male patient presented with a giant malignant
      peripheral nerve sheath tumor (MPNST) on his neck. Surgery was the chosen method
      of treatment by the help of a neurosurgeon for dissecting the mass from the
      nerves of the brachial plexus and a thoracic surgeon for removing the mass from
      the superior mediastinum. A mass of 2 kg in weight was excised gross totally. He
      had an early recurrence in the second month of the follow-up period despite
      postoperative irradiation therapy. He died of his disease due to the compression
      of vena cava superior.

PMID- 15488984
TI  - Tracheal juvenile xanthogranuloma in a child.
AB  - Juvenile xanthogranuloma is the most common form of non-Langerhans cell
      histiocytosis in children. It usually presents in the form of cutaneous lesions.
      Occasionally, the disease may affect other organs. Visceral forms are usually
      associated with cutaneous lesions, and are easily diagnosed. In isolated visceral
      occurrence, however diagnosis may prove difficult. Having the same spontaneous
      remission as cutaneous lesions, visceral lesions require treatment only in the
      case of serious dysfunction. We describe a case of isolated juvenile
      xanthogranuloma of the trachea, which has not previously been reported in
      children. The patient presented with serious respiratory symptoms that required
      immediate intervention.

PMID- 15488985
TI  - Ameloblastic fibroma of the maxillary sinus.
AB  - Ameloblastic fibroma is a rare true mixed tumor of odontogenic origin with both
      mesenchymal and ectodermal components. It usually arises from the mandibular
      dentition and presents in the second decade of life. It is a benign slow growing
      tumor that is less infiltrative than an ameloblastoma but tends to expand bone.
      It infrequently involves the maxilla and hence the management of these tumors in
      that region is controversial. The goal of therapy is to avoid cosmetic deformity
      without compromising on tumor eradication. We present the tenth reported case of
      this type of tumor in the maxilla, and the second one in an infant.

PMID- 15488986
TI  - Expression of genes coding melatonin and serotonin receptors in rodent skin.
AB  - Targeted search for expression of melatonin and serotonin receptors genes in the
      skin of C57BL/6J mice showed expression of MT1B (but not MT1A). Mouse skin and
      hamster melanomas also expressed 5HT2B and 5HT7. We identified two novel isoforms
      of MT1A and 5HT7.

PMID- 15488987
TI  - Putative tumor suppressor protein 4.1B is differentially expressed in kidney and
      brain via alternative promoters and 5' alternative splicing.
AB  - Protein 4.1B has been reported as a tumor suppressor in brain, but not in kidney,
      despite high expression in both tissues. Here we demonstrate that N-terminal
      variability in kidney and brain 4.1B isoforms arises through an unusual coupling
      of RNA processing events in the 5' region of the gene. We describe two
      transcriptional promoters at far upstream alternative exons 1A and 1B, and show
      that their respective transcripts splice differentially to exon 2'/2 in a manner
      that determines mRNA coding capacity. The consequence of this unique processing
      is that exon 1B transcripts initiate translation at AUG1 (in exon 2') and encode
      larger 4.1B isoforms with an N-terminal extension; exon 1A transcripts initiate
      translation at AUG2 (in exon 4) and encode smaller 4.1B isoforms. Tissue-specific
      differences in promoter utilization may thus explain the abundance of larger 4.1B
      isoforms in brain but not in kidney. In cell studies, differentiation of PC12
      cells was accompanied by translocation of large protein 4.1B isoforms into the
      nucleus. We propose that first exon specification is coupled to downstream
      splicing events, generating 4.1B isoforms with diverse roles in kidney and brain
      physiology, and potentially unique functions in cell proliferation and tumor
      suppression.

PMID- 15488988
TI  - The Nicotiana sylvestris extensin gene, Ext 1.2A, is expressed in the root
      transition zone and upon wounding.
AB  - The Ext 1.2A gene of Nicotiana sylvestris L. encoding an extensin, a cell wall
      structural protein, was characterized. Ext 1.2A encodes a polypeptide of 311
      amino acids having a highly repetitive structure and showing extensin features
      such as Ser-(Pro)(4) repeats and a high content of Tyr and Lys. The expression
      profile of the gene was demonstrated using the reporter GUS (beta-glucuronidase)
      fused to its promoter region (-630/+124, relative to the transcription start
      site) and by RNA gel blots. The results show that the (-630/+124) Ext 1.2A/GUS
      gene fusion is expressed in the root transition zone, where cells undergo an
      isodiametric growth but have not yet reached the rapid elongation phase, in stem
      inner and outer phloems and in cortical cells at the stem/petiole junction. The
      Ext 1.2A gene is also induced after wounding of stems, ribs, leaves or roots. The
      gene fusion is expressed in stem cortical cells, in ribs and at leaf edges upon
      wounding. These data suggest that the (-630/+124) promoter region contains
      regulatory elements responsible for expression in roots and stems, as well as for
      response to wounding in stems and leaves.

PMID- 15488989
TI  - A cDNA homologue of Schizosaccharomyces pombe cdc5(+) from the mushroom Lentinula
      edodes: characterization of the cDNA and its expressed product.
AB  - A cDNA homologue of Schizosaccharomyces pombe cdc5(+) was isolated from the
      basidiomycete mushroom Lentinula edodes and it was named Le.cdc5 cDNA. The
      deduced Le.CDC5 (842 amino acid residues) possessed N-terminal amino acid
      sequence highly homologous to those of S. pombe cdc5(+) gene product (Sp.cdc5p)
      and Sp.cdc5p-related proteins (SPCDC5RPs). The N-terminal 185 amino acid peptide
      of Le.CDC5 (Le.CDC5(1-185) peptide) produced in Escherichia coli was subjected to
      random binding-site selection analysis, revealing that Le.CDC5(1-185) peptide
      binds to a 7-bp sequence with the consensus sequence of 5'GCAATGT3'
      (complementary; 5'ACATTGC3'). Genomic binding-site (GBS) cloning by using
      Le.CDC5(1-185) peptide resulted in an isolation of the DNA fragment that
      contained three sets of 7-bp consensus-like sequence and TATA box. The Le.CDC5
      protein contained two putative phosphorylation sites of cAMP-dependent protein
      kinase (A kinase) in its C-terminus. There exists a possible leucine zipper
      between the two phosphorylation sites. The Le.CDC5 fragment containing the two
      phosphorylation sites was actually phosphorylated by commercially available A
      kinase. Yeast two-hybrid analysis suggested the homodimerization of Le.CDC5
      protein probably through the leucine zipper. Northern blot analysis showed that
      Le.cdc5 gene is most actively transcribed in primordia and small immature
      fruiting bodies of L. edodes, implying that Le.cdc5 may play a role in the
      beginning and early stage of fruiting-body formation.

PMID- 15488991
TI  - Mechanisms of glucocorticoid signalling.
AB  - It has become increasingly clear that glucocorticoid signalling not only
      comprises the binding of the glucocorticoid receptor (GR) to its response element
      (GRE), but also involves indirect regulation glucocorticoid-responsive genes by
      regulating or interacting with other transcription factors. In addition, they can
      directly regulate gene expression by binding to negative glucocorticoid response
      elements (nGREs), to simple GREs, to GREs, or to GREs and GRE half sites
      (GRE1/2s) that are part of a regulatory unit. A response unit allows a higher
      level of glucocorticoid induction than simple GREs and, in addition, allows the
      integration of tissue-specific information with the glucocorticoid response.
      Presumably, the complexity of such a glucocorticoid response unit (GRU) depends
      on the number of pathways that integrate at this unit. Because GRUs are often
      located at distant sites relative to the transcription-start site, the GRU has to
      find a way to communicate with the basal-transcription machinery. We propose that
      the activating signal of a distal enhancer can be relayed onto the transcription
      initiation complex by coupling elements located proximal to the promoter.

PMID- 15488990
TI  - Bovine glucose transporter GLUT8: cloning, expression, and developmental
      regulation in mammary gland.
AB  - GLUT8 is a newly identified member of the facilitative glucose transporter
      family, which characteristically exhibits high-affinity glucose transport
      activity. The expression of GLUT8 has been shown to depend on gonadotropin
      secretion in human testes and to be regulated by insulin in the blastocyst. To
      characterize GLUT8 and investigate its role in normal mammary gland function, we
      cloned and sequenced the full-length cDNA of bovine GLUT8. The 2073-base-pair
      cDNA sequence is predicted to encode a protein of 478 amino acids, with a
      molecular weight of approximately 51 kDa. The deduced amino acid sequence of
      bovine GLUT8 is 90%, 84%, 84% and 58% identical to human, mouse, rat and chicken
      GLUT8, and is 26%, 27% and 24% identical to bovine GLUT1, GLUT3 and GLUT4,
      respectively. Bovine GLUT8 retains the characteristic structural features of
      GLUT8 proteins previously identified from other species including membrane
      spanning helices, glucose transporter motifs, an N-linked glycosylation site on
      loop 9 and a putative dileucine internalization motif. The major in vitro
      transcription and translation product of bovine GLUT8 cDNA migrated at an
      apparent molecular weight of 38 kDa similar to the sizes reported for GLUT8 from
      other mammalian species. In the presence of canine microsomal membranes, the
      translation product increased to 40 kDa suggesting glycosylation. Transient
      transfection studies using a FLAG epitope tagged construct in COS-7 cells
      revealed that bovine GLUT8 is localized to the cytoplasm in non-stimulated
      conditions. A 2.1-kb GLUT8 mRNA transcript was detected at high levels in bovine
      testes, at moderate levels in lactating bovine mammary gland, lung, kidney,
      spleen, intestine and skeletal muscle, and at low levels in bovine liver. GLUT8
      mRNA expression in bovine mammary gland increased about 10-fold (P<0.001) during
      late pregnancy and early lactation, similar to the pattern of change in GLUT1
      mRNA and more dramatic than the increase seen in mouse mammary gland. These
      results suggest that GLUT8 expression may be regulated by lactogenic hormones and
      that GLUT8 may play a role in glucose uptake in the lactating mammary gland.

PMID- 15488993
TI  - Using burden of disease/cost-effectiveness as an instrument for district health
      planning: experiences from Uganda.
AB  - The burden of disease/cost-effectiveness analysis (BoD/CE) was introduced as a
      method for detailed planning and budgeting in 13 districts of Uganda. This
      endeavor can be seen as a "natural experiment", attempting to pursue policy
      implementation by means of a heavy focus on rationalistic/technical arguments as
      a main supportive factor. However, modern theory of policy implementation, e.g.
      the new institutionalism postulate that the implementation process is far from a
      passive diffusion process which only would need support by technical rationality,
      and that the result of the implementation process often is very different from
      prior expectations and depend on a number of factors in the so called translation
      process. The aim of this paper was to study the outcome of the mentioned "natural
      experiment" and, if the outcome diverted from the intended ones (which we
      hypothesized), to analyze some of the reasons for this by using the theoretical
      framework of new institutionalism. District budgets as well as actual
      expenditures before and after the introduction of the BoD and CE methods were
      analyzed. District health officials were interviewed to obtain their views and
      experiences of the method. Our study of budget allocations and actual
      expenditures revealed an increasing discrepancy from the pattern shown in the
      BoD/CE analysis. The district officials were positive about the methods but
      stated that it had to be used together with other methods. However, we found that
      the seemingly pure focus of BoD/CE, i.e. technical efficiency of budget
      allocations at the district level, collided with issues of accountability. The
      final budgets, and even more, the actual expenditures can be seen as the outcome
      of negotiation processes where other rationalities have considered, that is the
      translation process. This implies that the "technical" issue of efficiency has to
      become better understood and integrated in the notion of an accountable health
      care system at the district level. It is proposed that an increased involvement
      of the peripheral parts of the health care system, and most likely the target
      population itself, is needed to accomplish this.

PMID- 15488992
TI  - Cloning of the mismatch recognition protein MSH2 from zebrafish (Danio rerio) and
      its developmental stage-dependent mRNA expression.
AB  - Eukaryotic mismatch repair of simple base mispairs and small insertion-deletion
      loops is activated by the binding of a heterodimeric complex composed of MutS
      homolog 2(MSH2) and MSH6. Here we report the cloning of zebrafish (Danio rerio)
      MSH2 (zMSH2) cDNA that has an open reading frame of 2811 nucleotides encoding a
      polypeptide of 936 amino acids. The deduced amino acid sequence of zMSH2 shares a
      69% identity to both human and mouse MSH2. The zMSH2 protein contains a putative
      tyrosine-42 mismatch-contacting residue located at the N-terminal mismatch
      recognition region and four C-terminal ATP-binding consensus sequences conserved
      among MutS homologs. The 105-kDa recombinant zMSH2 bound apparently stronger to a
      G-T heteroduplex than to a homoduplex probe as shown by a gel shift assay. A
      preferential expression of both zMSH2 and zMSH6 mRNA in early embryos was found
      by Northern blot analysis. Whole mount in situ hybridization revealed a major
      expression of zMSH2 in different regions of the brain, including eyes,
      telencephalon, and the fourth ventricle in 12- to 48-h-old embryos. The
      production of zMSH2 mRNA gradually decreased in more mature 60- to 120-h-old
      zebrafish, reflecting a positive correlation between the amount of proliferating
      cells and MSH gene expression.

PMID- 15488994
TI  - Resource allocation equity in northeastern Mexico.
AB  - Currently, the population health needs are unlimited, but allocation of financial
      resources is not in accordance with these needs, probably due to the lack of
      specific information. In this work, we propose a new approach to allocate
      resources with equity as a tool for decision-making in planning. The grade of
      equity in resource allocation in decentralized management medical areas (DMMAs
      (AMGD, for its initials in Spanish)) was determined; these are limited
      geographical areas of a social security institution in three states of the
      northeastern region of Mexico. The areas with more health needs in the global
      index were DMMA no. 12 in Tamaulipas with a Z-score (ZS) of -5; area no. 3 in
      Coahuila with -4; and area no. 9 in Nuevo Leon, no. 16 and no. 17 in Tamaulipas
      with -2. Equity was measured according to the degree of concordance between the
      health needs index and the per capita health expenditure of each area: (r = 0.19,
      P > 0.05). Low concordance was found between these variables in the studied
      medical areas.

PMID- 15488995
TI  - Consumer involvement in decisions about what health-related research is funded.
AB  - OBJECTIVES: To consider whether, why and how research funders involve consumers
      in decisions about what health-related research is funded. METHODS: Postal survey
      and semi-structured interviews with UK funders of health-related research.
      RESULTS: Organisations that fund research have diverse goals and remits, and
      perceive themselves to be accountable in different ways and to different groups.
      They have a variety of reasons for involving consumers in decisions about what
      research is funded, but also a number of concerns about doing so-particularly
      about the ways in which consumer input might 'distort' the research agenda.
      Research funders use several types of decision-making structures and processes to
      identify and prioritise topics in which they want to invest and to select between
      research proposals. They involve consumers in these structures and processes in
      diverse ways. Little is known about the actual effects of this involvement, but
      the nature and extent of consumer influence on the research agenda is likely to
      be moderated by a number of factors, including the types of consumers involved,
      the particular structures and processes in which they are involved, the timing of
      their input and the different ways in which they are asked to contribute in
      relation to others. CONCLUSIONS: Diverse research funding organisations are now
      involving consumers in the various approaches that they take to identify and
      prioritise research topics and to decide which proposals they will fund. The
      future development of their activities could usefully be informed by careful
      consideration not just of consumer involvement but of the implications of the
      various structures and processes that shape research agendas. The appropriateness
      of particular forms of consumer involvement should be considered in the broader
      context of the features of the whole research funding system, including the
      values implicit within it.

PMID- 15488996
TI  - Ulysses directives in The Netherlands: opinions of psychiatrists and clients.
AB  - In this article we present a study on the opinions of Dutch psychiatrists and
      clients on Ulysses directives. In-depth interviews were conducted with 18 clients
      and 17 psychiatrists. Most respondents were proponents of Ulysses directives. The
      most frequently mentioned objective of these directives was to secure timely
      admission to hospital, although a large minority was mainly interested in giving
      patients influence on treatment decisions. Psychiatrists differed on how much
      autonomy they preferred with regard to decisions about the moment of admission
      and kind of treatment. Clients also differed in this respect. Pressure from
      others to execute a Ulysses directive, and premature admission to the hospital
      were mentioned as risks of Ulysses directives. Crisis cards were seen as an
      alternative by many psychiatrists and some clients. Recommendations are made for
      a good functioning of Ulysses directives, and the appropriateness of crisis cards
      as an alternative for a number of patients is discussed.

PMID- 15488997
TI  - Primary health care in practice: is it effective?
AB  - Primary health care is accepted as the model for delivering basic health care to
      low income populations in developing countries. Using El Salvador as a case
      study, the paper draws on three data sets and a qualitative survey to assess
      health care access and utilization across public and private sector options
      (including NGOs). Multivariate analysis is used to estimate the quantitative
      determinants of health seeking behavior. Physical and financial access is
      generally good. Households do not value the community health workers, and prefer
      high cost private care, even the poorest families, because of the lower waiting
      times and higher probability of successful treatment. Similarly, higher level
      public facilities--health centers and hospitals--are preferred because they are
      less costly in terms of time as they offer "one stop shopping" and do not require
      multiple visits, and treatment success is higher than among health posts, health
      units or community health workers. These results combined with the small size of
      El Salvador suggest that alternative strategies to community health workers may
      be a more cost effective approach. While prevention is desirable, community
      health workers do not have the skills or services that the communities value,
      which makes them less effective in promoting prevention. Alternative modes of
      reaching the community could reduce costs and raise the effectiveness of public
      health spending.

PMID- 15488998
TI  - Global public health mandates in a diverse world: the polio eradication
      initiative and the expanded programme on immunization in sub-Saharan Africa and
      South Asia.
AB  - BACKGROUND: The circulation of wild poliovirus is expected to cease soon due to
      the success of the global polio eradication initiative. Thereafter, intensified
      polio eradication efforts such as National Immunisation Days (NIDs) will most
      likely be discontinued. As a consequence, the expanded programme on immunization
      (EPI) will no longer enjoy extra inputs from the polio eradication initiative. We
      investigated whether today's EPIs are ensuring universal and equitable vaccine
      coverage; and whether the removal of extra inputs associated with the
      implementation of NIDs is likely to affect EPI coverage and equity. METHODS:
      Using data from Demographic and Health Surveys conducted in 15 countries of South
      Asia and Africa during 1990-2001, we examined absolute levels of EPI coverage;
      changes in EPI coverage after the introduction of NIDs; and relative coverage
      according to urban versus rural residence, higher versus lower education of
      mothers, and wealthiest vs. poorest population segment. RESULTS: Polio and non
      polio antigen coverage increased in seven countries during the study period.
      Substantial inequalities in coverage of non-polio antigens persist, however,
      translating into inequities in the risk of contracting vaccine preventable
      diseases. In some African countries, routine EPI coverage and/or equity declined
      during the study period. In these countries, any positive effect of NIDs on the
      EPI coverage must have been small, relative to the negative effects of declining
      economies or deteriorating health systems. In Nigeria, Zimbabwe, Kenya and
      Malawi, even polio coverage declined, in spite of the introduction of NIDs.
      CONCLUSION: As additional inputs associated with polio eradication will cease,
      routine EPI services need to be strengthened substantially in order to maintain
      levels of population immunity against polio and to improve social equity in the
      coverage of non-polio EPI antigens. Our findings imply that this aim will require
      additional inputs, particularly in African countries.

PMID- 15488999
TI  - Ghrelin and reproduction: a novel signal linking energy status and fertility?
AB  - Ghrelin was originally identified in 1999 as the endogenous ligand of the growth
      hormone (GH) secretagogue receptor (GHS-R). Since then, an ever growing number of
      publications have reported the potential involvement of this molecule in the
      regulation of a large array of endocrine and non-endocrine functions, including
      the control of GH secretion and several other neuroendocrine axes as well as food
      intake and energy balance. On the basis of its proposed role as indicator of
      energy insufficiency and the proven reproductive effects of other regulators of
      energy homeostasis and growth (such as the adipocyte-derived hormone leptin), it
      is tempting to hypothesize that ghrelin might play a role in the control of
      reproductive function and fertility. Indeed, although evidences in this area are
      still fragmentary, we review herein data from different research groups, which
      have recently substantiated the reproductive facets of this newly identified
      hormone. Thus, expression of ghrelin has been demonstrated in human and rodent
      placenta, and ghrelin has been reported to inhibit early embryo development. In
      addition, ghrelin was shown to suppress luteinizing hormone (LH) secretion in
      vivo, and to decrease LH responsiveness to LH-releasing hormone (LHRH) in vitro.
      Moreover, ghrelin was able to inhibit stimulated testicular testosterone
      secretion, whereas androgens have been proven independent modulators of
      circulating ghrelin levels. In this context, our group has recently provided
      extensive evidence for the expression of ghrelin and its putative receptor, the
      type 1a GHS-R, in rat and human gonads. Testicular expression of ghrelin was
      highly selective for mature Leydig cells and under the hormonal control of
      pituitary LH, while in the ovary, expression of ghrelin was demonstrated in
      steroidogenically active luteal cells and interstitial hilus cells. Likewise,
      expression of GHS-R type 1a was demonstrated in Sertoli and Leydig cells of the
      testis and follicular, luteal and interstitial hilus cells in the ovary. In
      summary, the data so far available indicate that ghrelin may operate at different
      levels of the reproductive system, including the testis and the ovary, which are
      potential targets for systemic ghrelin actions. In addition, ghrelin is produced
      locally within the human and rodent gonads, where the presence of both components
      (ligand and receptor) of ghrelin signaling system is highly suggestive of a
      conserved regulatory role for this newly discovered molecule in the regulation of
      mammalian gonadal function. Overall, it is proposed that ghrelin may cooperate
      with other regulatory signals, such as leptin, in the integrated control of
      energy balance and reproduction.

PMID- 15489000
TI  - Down-regulation of vascular endothelial growth factor in renal cell carcinoma
      cells by glucocorticoids.
AB  - Metastatic renal cell carcinomas (RCC) remain highly resistant to systemic
      therapy. RCCs are highly vascular tumors, which overproduce angiogenic peptides
      such as vascular endothelial growth factor (VEGF) even under normoxic conditions.
      A potential suggested role of antiangiogenic therapeutic strategies is the
      treatment of RCC by inhibiting VEGF production. The down-regulation of VEGF
      expression by glucocorticoids has recently been demonstrated in several cells. In
      this study, the direct effects of glucocorticoids on VEGF production by RCC cells
      were evaluated. Four RCC cell lines A498, RCC270, Caki1, and ACHN were treated
      with dexamethasone (DEX), hydrocortisone (HC), 5-alpha-dihydrotestosterone (DHT),
      or estradiol (E2). RU486 was used as a glucocorticoid receptor (GR) antagonist.
      Cell growth was studied with MTS assays. VEGF mRNA and protein were evaluated
      with quantitative real-time RT-PCR and ELISA, respectively, and GR expression was
      examined using RT-PCR and immunocytochemistry. All four RCC cell lines expressed
      GR. DEX at 100 nM down-regulated VEGF secretions by more than 50% in three lines
      (A498, RCC270, and Caki1) and had a weak inhibitory effect on ACHN cells. The
      effect of DEX on reducing VEGF mRNA levels in A498 cells was concentration
      dependent and maximal at 100 nM (80% inhibition). HC had similar but weaker
      effects on VEGF production in the RCC cells, but E2 and DHT had no effect. RU486
      reversed the effects of DEX. DEX at 1-1000 nM did not affect cell growth in any
      of the four RCC cell lines. This is the first study showing that glucocorticoids,
      at concentrations achievable in vivo by oral administration of low doses of DEX,
      have an inhibitory effect on VEGF mRNA expression and protein secretion of RCC
      cells possibly through the GR pathway. Furthermore, DEX might have a potential
      role in antiangiogenic therapeutic strategies by inhibiting VEGF production
      during metastatic RCC treatment.

PMID- 15489001
TI  - Thyroid hormone stimulates myoglobin gene expression in rat cardiac muscle.
AB  - T3 increases the heart activity, O2 consumption and the reactive O2 species
      production. Myoglobin (Mb) is highly expressed in the heart, where it facilitates
      O2 diffusion, mitochondrial respiration, and scavenges reactive O2 species. Here
      we investigate, by dose-response (0.3-100 microg/100 g BW, i.p., 5 days) and time
      course studies (100 microg/100 g BW, i.v., from 0.5 to 24h), whether T3 affects
      the Mb mRNA and protein expression in atrium (A) and ventricle (V), by Northern
      and Western blot. We show that the Mb gene is controlled by T3 in A and V, as
      indicated by Mb mRNA and protein content decrease in thyroidectomized (Tx) rats,
      and restoration by T3 treatment. In the A, the different doses of T3 induced the
      Mb mRNA and protein recovery to the euthyroid levels; in the time-course study,
      this occurred only with the protein levels. In the V, T3 progressively increased
      the Mb mRNA above the euthyroid levels at a dose of 25 microg/100g BW; higher
      doses decreased it to the euthyroid levels. Mb protein increased only to the
      euthyroid levels at all T3 doses injected. The time-course study showed a
      progressive increase in the ventricular Mb mRNA and protein, which exceeded the
      euthyroid levels from 6 to 24h, and at 2 and 6 h of the T3 treatment,
      respectively. We conclude that heart Mb gene expression is influenced by thyroid
      status.

PMID- 15489002
TI  - Characterization of vitamin D-mediated induction of the CYP 24 transcription.
AB  - Transcription of the CYP24 (25-hydroxyvitamin D(3)-24-hydroxylase) gene is known
      to be induced by 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). We studied the
      induction kinetics in detail in human skin-derived fibroblasts. While the basal
      transcription of this gene was very low, addition of 1,25(OH)2D3 increased the
      mRNA level by 50-fold within 1h. The induction reached as high as 20000-fold
      after 12h. DNA microarray analysis also indicated that the induction ratio of the
      CYP24 gene is exceptionally high among 3800 human genes examined. The increase of
      mRNA was caused by stimulation of the transcription, but not by stabilization of
      mRNA. 24(R),25-dihydroxyvitamin D3 (24,25(OH)2D3), a compound metabolically
      related to 1,25(OH)2D3, also stimulated the CYP24 gene transcription, though at
      much higher concentrations. However, this stimulation was significantly augmented
      by synergistic actions of 24,25(OH)2D3 and 1,25(OH)2D3, suggesting that
      24,25(OH)2D3 or its metabolites might be playing some roles in the regulation of
      CYP24 gene transcription.

PMID- 15489003
TI  - Intracellular signaling involved in estrogen regulation of serotonin reuptake.
AB  - 17beta-estradiol (E2) regulates neuronal activity via genomic and rapid, non
      genomic mechanisms. The rat serotonergic neuronal cell line (RN46A) was used to
      investigate the rapid effects of E2 on serotonin (5-HT) reuptake and on potential
      intracellular signaling pathways. RN46A cells express the serotonin transporter
      (SERT) and estrogen receptor (ER)beta, but not ERalpha. Fifteen minute E2
      treatment (10(-9)M) decreased 5-HT uptake. Intracellular cAMP levels were not
      increased by 15 min E2 treatment; however, E2 caused an increase in intracellular
      Ca2+ levels, with a maximum response within the first minute. The response was E2
      specific, since other steroids (17alpha-estradiol, testosterone, and
      progesterone) had no effect. The ER antagonist ICI 182,780 blocked the rapid E2
      effects on intracellular Ca2+ levels as did the selective ER modulator tamoxifen.
      In summary, changes in intracellular Ca2+ levels caused by E2 and mediated
      through ERbeta may be responsible for observed rapid effects of E2 on SERT
      activity.

PMID- 15489004
TI  - Molecular interaction of retinoic acid receptors with coregulators PCAF and
      RIP140.
AB  - p300/CBP-associating factor (PCAF) is a ligand-dependent coactivator, whereas
      receptor-interacting protein 140 (RIP140) is a ligand-dependent negative
      coregulator for retinoic acid (RA) receptor (RAR) and retinoid X receptor (RXR).
      To compare these molecular interactions and to determine the effect of RXR
      ligands, we focus on PCAF/RAR/RXR complex formation in this study for a
      comparison to RIP140/RAR/RXR complex formation. The LBD of RXR is identified as
      its primary PCAF-interacting motif. BIAcore studies determine the Kd of RAR/RXR
      association with PCAF as 9.35 nM in the presence of RXR ligand AGN194204, and
      47.2 nM in the absence of ligand. Cross-linking study demonstrates tri-molecular
      complex consisting of one RAR/RXR pair and one PCAF. In competition experiments,
      RIP140 strongly competes with PCAF for interaction with RAR/RXR both in vitro and
      in vivo. Chromatin immunoprecipitation demonstrates recruitment of RIP140 and
      PCAF to the endogenous RA-regulated gene, the RARbeta2 promoter. This study
      presents kinetic evidence for competition of RIP140 with PCAF for ligand
      dependent interactions with RAR/RXR, and provides kinetic explanation for the
      suppressive activity of RIP140 in RA-activated gene expression.

PMID- 15489005
TI  - Transcription factor GATA-6 is expressed in the endocrine and GATA-4 in the
      exocrine pancreas.
AB  - GATA-4 and GATA-6 are zinc finger transcription factors that regulate gene
      expression, differentiation, and cell proliferation in various tissues. These
      factors have been implicated in the development of endodermal derivatives,
      including epithelial cells in the yolk sac, lung, and stomach. In the present
      study, we have characterized the expression of GATA-4 and GATA-6 during
      development of another endodermal derivative, the mouse pancreas, using a
      combination of in situ hybridization and immunohistochemistry. Neither GATA-4 nor
      GATA-6 antigen was detected in E10.5 pancreatic epithelial buds expressing Pdx-1.
      By E15.5, GATA-4 mRNA and protein were evident in developing pancreatic acini,
      but not in ductal or endocrine cells of the pancreas; GATA-6 mRNA and protein
      were present in both endocrine and exocrine cell precursors. In the newborn and
      adult pancreas, GATA-4 protein was seen in acinar cells, while GATA-6 antigen was
      found mainly in islet beta-cells. The amphicrine pancreatic AR42J-B13 cell line
      was used to study the expression of GATA-4 and GATA-6 during the differentiation
      of these cells towards an endocrine phenotype. Endocrine differentiation was
      associated with marked increase in GATA-6 but not GATA-4 mRNA levels. We conclude
      that GATA-4 is a marker of exocrine pancreatic differentiation, whereas GATA-6 is
      a marker of endocrine pancreatic development.

PMID- 15489006
TI  - Circadian regulation of islet genes involved in insulin production and secretion.
AB  - Both transcription factors albumin site d-binding protein (DBP) and thyrotroph
      embryonic factor (TEF) are elements of the "cell-clock". Their circadian
      accumulation in suprachiasmatic nucleus (SCN) and peripheral tissues such as
      liver, kidney and lung is thought to participate in controlling circadian
      regulation of downstream genes. TEF and DBP control elements have never been
      investigated in the insulin-secreting cells, but impairment of the circadian
      rhythm of the beta-cells might be involved in the development of diabetic state
      as type 2 diabetics have lost daily temporal variations of insulin secretion. We
      investigated the expression pattern of TEF and DBP in insulin-secreting cells.
      TEF and DBP transcripts are expressed at extremely high levels in human
      pancreatic islets compared to other tissues, suggesting a potentially important
      circadian regulation of these cells. Both TEF and DPB accumulate in a circadian
      way in insulin-secreting cells after a serum shock known to restore circadian
      rhythms in cultured cells. In addition, the expression of islet-specific genes
      involved in glucose sensing (glucose transporter 2 (Glut2), glucokinase), insulin
      production (insulin) and secretion (migration inhibitory factor (MIF),
      somatostatin and syntaxin 1A) were modulated in the same daily rhythm as well.
      The circadian deregulation of these genes could therefore participate in the
      diabetic state development.

PMID- 15489007
TI  - Grafts of immortalized chromaffin cells bio-engineered to improve met-enkephalin
      release also reduce formalin-evoked c-fos expression in rat spinal cord.
AB  - Transplantation of adrenal medullary tissue for terminal cancer pain has been
      tested clinically, but this approach is not practical for routine use because of
      the shortage of organ donors and lack of tissue homogeneity. As a first
      alternative step, we have generated immortalized chromaffin cells over-expressing
      opioid peptides, namely met-enkephalin. Rat chromaffin cells have been
      genetically modified with vectors containing expression cassettes with either
      synthetic met-enkephalin or pro-enkephalin gene coding regions, fused with the
      nerve growth factor signal peptide for secretion. After stable transfection and
      differentiation in vitro, met-enkephalin and pro-enkephalin cells had higher met
      enkephalin immunoreactivity and secreted met-enkephalin levels, compared to
      control cells containing the expression vector only. In the formalin hindpaw
      injection model, 15 days after subarachnoid transplant of cells, grafts of met
      enkephalin and pro-enkephalin cells significantly reduced the number of formalin
      evoked c-fos immunoreactive spinal neurons in the spinal cord, compared to grafts
      of vector-alone chromaffin cells. The use of such expandable cell lines, for
      chronic spinal delivery of opiates, could offer an attractive and safe
      alternative strategy based on ex vivo gene therapy for the control of opioid
      sensitive chronic pain.

PMID- 15489008
TI  - The bovine iris-ciliary epithelium expresses components of rod phototransduction.
AB  - Earlier studies have documented that the iris in lower vertebrates is
      photosensitive. In the present work, we examined whether the bovine iris which
      exhibits a common embryonic origin with the ocular ciliary epithelium and the
      neural retina, expresses components of phototransduction. By Northern blot and RT
      PCR amplification we detected in the iris, rhodopsin, rhodopsin kinase and
      arrestin transcripts and DNA products, respectively, of the same size as in the
      retina. By Western blot, antibodies to rhodopsin, rhodopsin kinase and arrestin
      detected low levels of protein with similar molecular masses as in the retina.
      Transient transfections of bovine iris cells in vitro with rhodopsin promoter
      luciferase-reporter constructs (p130-Luc, p176-Luc, 1225-Luc and p2000-Luc)
      containing proximal and distal promoter elements led to a significant stimulation
      of promoter activity over the basal activity. In particular, the construct p225
      Luc containing proximal promoter elements upstream of the transcription start
      site (-225 to +70 bp) led to 3.1-fold stimulation of activity over p176-Luc, 2.1
      fold over p130 or p2000-Luc and 190-fold over the basal activity. These results
      suggested that the bovine iris cells contain factors that could either stimulate
      or attenuate rhodopsin transcription. The data also supported the view that
      components associated with non-visual phototransduction are expressed in
      extraretinal sites including the ciliary epithelium and the iris.

PMID- 15489009
TI  - Evidence of early neurobiological alternations in adolescents with posttraumatic
      stress disorder: a functional MRI study.
AB  - Neuroimaging studies of patients with posttraumatic stress disorder (PTSD) have
      largely been performed in adult populations. The purpose of the current study was
      to investigate neural correlates of PTSD in adolescents. Specifically, this study
      investigates whether a differential brain response was present during the visual
      perception and imaginary recollection of traumatic reminders in adolescents who
      developed PTSD versus those who did not after experiencing earthquake. Eleven
      Taiwanese adolescents (age range: 12-14 years) with traumatic experience of
      earthquake were enrolled. Five subjects fulfilled PTSD criteria, while the other
      six served as non-PTSD controls. Brain activation was measured by functional
      magnetic resonance image (fMRI) during visual perception and imagery recall of
      earthquake and neutral pictures at 14 months after earthquake. During earthquake
      imagery (as compared with neutral imagery), PTSD group demonstrated activation in
      the bilateral visual cortex, bilateral cerebellum and left parahippocampal gyrus,
      while control group did not. During earthquake perception (as compared with
      neutral perception), the control group showed activation over anterior cingulate,
      but the PTSD group did not. Intergroup comparison confirmed above discrepancies
      was significant. We concluded that neurobiological alternation of PTSD in
      adolescent was similar to those in adult and might have developed within 14
      months after trauma exposure.

PMID- 15489010
TI  - Mental motor imagery and the body schema: evidence for proprioceptive dominance.
AB  - Previous studies have demonstrated that both visual and proprioceptive feedback
      influence motor control. The relative contributions of these sensory modalities
      to the on-line computation of body position--that is, the body schema--remain
      unclear. We report a study designed to explore the roles of vision and
      proprioception in motor planning. The task required subjects to judge if a
      pictured stimulus was a right or left hand; stimuli included pictures of a right
      or left hand in a palm up or palm down position and in six different angular
      rotations (0 degrees , 60 degrees , 120 degrees , 180 degrees , 240 degrees , 300
      degrees ). Each subject was tested with his/her right hand palm down and palm up.
      There were three conditions: a "control" condition (real hand in view), a "fake
      hand" condition (fake hand in view, real hand out of view), and a
      "proprioception" condition (no fake hand, real hand out of view). We found that
      proprioceptive input (that is, the subject's "felt position") had a significant
      influence on mental rotation whereas the visually perceived posture of the hand
      did not. We suggest that, at least under some circumstances, proprioceptive
      inflow may represent the dominant sensory input to the on-line representation of
      the body in space.

PMID- 15489011
TI  - Cerebellar interpositus nuclear inputs impinge on paraventricular neurons of the
      hypothalamus in rats.
AB  - Several reports have indicated that the cerebellum is involved in regulation of
      some non-somatic activities through the cerebellohypothalamic projections.
      Therefore, the modulatory effects of the cerebellar interpositus nucleus (IN) on
      neuronal activity of the paraventricular nucleus of the hypothalamus (PVN) was
      investigated in this study by using in vivo extracellular recording technique in
      rats. We recorded from 115 PVN neurons, 51 (44.3%) responded to the cerebellar IN
      stimulation. Of the responsive PVN neurons tested for their sensitivity to
      hypertensive and/or hyperosmotic stimulations, 66.7% (6/9) and 75.0% (6/8)
      responded to intravenous metaraminol and hypertonic saline administration,
      respectively. These results demonstrate that the cerebellar IN afferent inputs
      impinge on the PVN neurons, including those baroreflex-sensitive and
      osmoresponsive neurons, suggesting that the cerebellum may actively participate
      in the cardiovascular regulation and osmoregulation through the
      cerebellohypothalamic projections.

PMID- 15489012
TI  - Delayed expressed TNFR1 co-localize with ICAM-1 in astrocyte in mice brain after
      transient focal ischemia.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is expressed after brain ischemia and
      is participated in the induction of neuronal cell death. Recently, we have
      reported that ICAM-1 is localized in astrocytes in the chronic phase of ischemia.
      However, the regulation of astroglial ICAM-1 after brain ischemia is not
      elucidated in detail. Therefore, we examined the gene and protein expression of
      TNFR1 after transient middle cerebral artery occlusion (tMCAO) by using real time
      PCR and immunohistochemistry. Moreover, we determined the relationship of TNFR1
      and ICAM-1 in the astrocyte in chronic phase of ischemia. Increased expression of
      TNFR1 mRNA in the ipsilateral cortex was noted slightly during ischemia and was
      significantly increased at 12 h after reperfusion. Few TNFR1-like
      imuunoreactivity (TNFR1-LI) was observed in the cortex of normal animals.
      However, TNFR1-LI was increased at 1 h during ischemia, then it was decreased at
      3-6 h, and was increased again at 12-24 h after reperfusion in the core of
      ischemic area. TNFR1-LI was demonstrated in both neurons and astrocytes but not
      in oligodendrocytes and microglia/macrophages at 24 h after reperfusion. At 96 h
      after tMCAO, TNFR1-LI was increased in the perifocal region and it appeared to be
      displayed the astrocyte-like cells. By use of double immunostaining method, we
      found that the ICAM-1-LI was overlapped with GFAP-LI. Our data indicates that the
      expression of TNFR1 is up-regulated in accordance with ischemic insult and
      delayed expressed TNFR1-LI co-localized with ICAM-1-LI in astrocytes after tMCAO.
      These results suggest that astroglial ICAM-1 is regulated by TNF-alpha dependent
      pathway.

PMID- 15489013
TI  - Heart fatty acid binding protein as a potential diagnostic marker for
      neurodegenerative diseases.
AB  - The diagnosis of neurodegenerative diseases with dementias requires several
      different test approaches and often remains uncertain. Using a proteomic approach
      it was shown in nine patients that heart fatty acid binding protein (H-FABP)
      might be a biomarker for Creutzfeldt-Jakob disease (CJD). The aim of our study
      was to evaluate whether H-FABP is a biomarker for the differential diagnosis of
      dementias. Therefore we measured H-FABP in cerebrospinal fluid (CSF) and serum of
      patients having CJD, dementia with Lewy-bodies (DLB), Alzheimer's disease (AD)
      and in non-demented control (NDC) patients. H-FABP levels in CSF and serum of CJD
      patients are increased compared to non-demented controls. Levels of H-FABP were
      significantly higher in CJD patients compared to AD and DLB in CSF. However,
      discrimination between CJD and AD was not possible in serum. Interestingly,
      highest levels of H-FABP were found in serum of DLB patients. Our results suggest
      that H-FABP might be a useful biomarker for the differentiation between the
      dementias examined if levels in CSF and serum are determined in parallel.

PMID- 15489014
TI  - Chronic non-invasive glucocorticoid administration decreases polysialylated
      neural cell adhesion molecule expression in the adult rat dentate gyrus.
AB  - The expression of the polysialylated neural cell adhesion molecule (PSA-NCAM) is
      increased in the hippocampus after chronic restraint stress (CRS) and may play a
      permissive role in structural changes that include dendrite reorganization in
      dentate gyrus (DG) and CA3 pyramidal neurons and suppression of neurogenesis in
      DG. We report that chronic oral corticosterone (CORT) administration decreases
      the number of PSA-NCAM immunoreactive granule neurons in the adult rat dentate
      gyrus, and the available evidence suggests that this is an indirect effect of
      CORT, possibly involving excitatory amino acids, that may not be directly related
      to neurogenesis. Because CORT treatment reduces but does not eliminate PSA-NCAM
      expression, the present results do not exclude a permissive role for PSA-NCAM in
      CORT or CRS-induced structural plasticity in hippocampus.

PMID- 15489015
TI  - An antioxidant tetrapeptide UPF1 in rats has a neuroprotective effect in
      transient global brain ischemia.
AB  - Different glutathione analogues have potential to maintain or increase tissue
      glutathione level and to scavenge the reactive oxygen species. We designed and
      synthesized a novel non-toxic glutathione analogue, named UPF1, which possessed
      60-fold higher hydroxyl radical scavenger efficiency in vitro, compared with
      glutathione itself, and investigated the effects of UPF1 on a four-vessel
      occlusion model of rats. The UPF1 was administered via the jugular vein in two
      separate experiments at two time points: 20 min before global brain ischemia and
      immediately before reperfusion. In both cases the number of pyramidal cells
      surviving in the subfield of CA1 at the dorsal hippocampus in the UPF1-treated
      groups of rats was twice as high as in the vehicle group.

PMID- 15489016
TI  - Ethanol-induced reduction of neurotrophin secretion in neonatal rat cerebellar
      granule cells is mitigated by vitamin E.
AB  - Ethanol exposure during nervous system development produces a range of
      abnormalities, and in humans may lead to the fetal alcohol syndrome. Among the
      mechanisms hypothesized to play roles in ethanol neurotoxicity are altered
      expression of supportive neurotrophic factors (NTFs), and cellular disturbances
      in oxidative processes. In this study, ethanol effects on secretion of two NTFs,
      brain-derived neurotrophic factor, and neurotrophin-3 were analyzed in neonatal
      rat cerebellar granule cells, and the potential of the antioxidant vitamin E to
      modulate ethanol effects was investigated. Ethanol exposure in these preparations
      reduced NTF secretion, but vitamin E appreciably ameliorated the ethanol effects.
      Possible mechanisms underlying both the ethanol effects on NTF secretion, and the
      protection of this antioxidant are considered.

PMID- 15489017
TI  - Cloning and pharmacological characterization of mouse TRPV1.
AB  - The Transient Receptor Potential cation channel V1 (TRPV1) is expressed in
      peripheral nociceptive neurons and is subject to polymodal activation via various
      agents including capsaicin, noxious heat, low extracellular pH, and direct
      phosphorylation by protein kinase C (PKC). We have cloned and heterologously
      expressed mouse TRPV1 (mTRPV1) and characterized its function utilizing FLIPR
      based calcium imaging to measure functional responses to various small molecule
      agonists, low pH and direct phosphorylation via PKC. The various TRPV1 agonists
      activated mTRPV1 with a rank order of agonist potency of (resiniferatoxin (RTX) =
      arvanil > capsaicin = olvanil > OLDA > PPAHV) (EC50 values of 0.15+/-0.04 nM,
      0.27+/-0.07 nM, 9.1+/-1.2 nM, 3.7+/-0.3 nM, 258+/-105 nM, and 667+/-151 nM,
      respectively). Additionally, mTRPV1 was activated by either low pH or with
      addition of the PKC activator phorbol 12-myristate 13-acetate (PMA). The TRPV1
      antagonists iodinated-resiniferatoxin (I-RTX) or BCTC were both able to block
      capsaicin, pH and PKC-induced responses of mTRPV1 (IC50 (I-RTX) = 0.35+/-0.12 nM,
      1.9+/-0.7 nM, and 0.80+/-0.68 nM, IC50 (BCTC) = 1.3+/-0.36 nM, 0.59+/-0.16 nM,
      and 0.37+/-0.15 nM, respectively). However, the antagonist capsazepine was only
      able to inhibit a capsaicin-evoked response of mTRPV1 with an IC50 of 1426+/-316
      nM. Comparable results were achieved with rat TRPV1, while capsazepine blocked
      all modes of human TRPV1 activation. Thus, the mTRPV1 cation channel has a
      molecular pharmacological profile more akin to rat TRPV1 than either human or
      guinea pig TRPV1 and the molecular pharmacology suggests that capsazepine may be
      an ineffective TRPV1 antagonist for in vivo models of inflammatory pain in the
      mouse.

PMID- 15489018
TI  - Neuroprotective effects of beta-secretase inhibitors against rat retinal ganglion
      cell death.
AB  - Beta-secretase, an enzyme participating in amyloid beta-peptide generation, is
      thought to be involved in the pathogenesis of Alzheimer's disease. We examined
      the effects of beta-secretase inhibitors such as N-benzyloxycarbonyl-Val-Leu
      leucinal (Z-VLL-CHO) and H-EVNstatineVAEF-NH2 (GL-189) on glutamate-induced
      retinal ganglion cell (RGC) death in vitro. In cultures of purified RGCs from
      neonatal rats, 2-day exposure to 25 microM glutamate induced RGC death, and Z-VLL
      CHO (100 nM) and GL-189 (1 microM) had neuroprotective effects. We also found out
      that Z-VLL-CHO showed a neuroprotective effect on retinal damage induced by optic
      nerve crush in vivo. Thus, beta-secretase could be a potential target for therapy
      of neurodegenerative retinal diseases.

PMID- 15489019
TI  - Effect of mood state on anticipatory postural adjustments.
AB  - Static postural control has been demonstrated to link with psychological state.
      However, the effect of psychological state on dynamic postural control remains
      unclear. In this study, we examined the effect of mood state on anticipatory
      postural adjustment (APA), one of the most important functions for dynamic
      postural control. Fourteen healthy male subjects performed unilateral arm
      elevation tasks after completing a Profile of Mood States (POMS) questionnaire.
      Mood state measured by POMS and the latency or amplitude of the APA in the
      ventral muscles (rectus femoris, tibialis anterior) of the lower limb showed
      significant negative correlations. The correlation between the mood state and APA
      amplitude in the soleus was found to be significantly positive. There were
      significant negative correlations between the mood state and reaction-time. These
      findings suggest that it is possible that dynamic postural control is affected by
      mood state.

PMID- 15489020
TI  - Human sensorimotor tracking of continuous subliminal deviations from isochrony.
AB  - We show that people continuously react to time perturbations in the range 3-96 ms
      in otherwise isochronous sound sequences. Musically trained and untrained
      participants were asked to synchronize with a sequence of sounds, and these two
      groups performed almost equally below the threshold for conscious detection of
      the perturbations. Above this threshold the motor reactions accounted for a
      larger proportion of the stimulus deviations in musically trained participants.

PMID- 15489021
TI  - Sensitivity to pain and c-Fos expression in brain structures in rats.
AB  - The induction of c-Fos protein--a product of the c-fos gene, a marker of changes
      in neuronal activity, was studied in brain structures of animals differing in
      their sensitivity to the acute painful stimulation, a foot-shock (MS--more
      sensitive rats; LS--less sensitive rats, according to the arbitrary criterion in
      the flinch-jump pretest). After the pretest the animals were dived into the
      control group, exposed on retest 10 days later to the testing cage only (C1
      group), and aversively stimulated animals (MS and LS groups, given five mild
      footshocks 1.5 h before immunocytochemical part of the experiment). Additional
      control group of naive, intact animals, was studied in parallel (C group). It was
      shown that animals subjected to the flinch-jump test retained a strong emotional
      reaction on re-exposure to the shock cage on retest (a conditioned fear) 10 days
      later, as revealed by the widespread expression of c-Fos protein in the examined
      brain structures, as compared with the control, naive rats not exposed to the
      testing cage. In the lateral habenular nucleus (LHAB) a similar effect has been
      found in the control animals re-exposed to the testing cage only (C1 group), and
      in the MS group, suggesting that this brain area participates predominantly in
      processing of emotional-cognitive component of a painful stimulation. In the
      periaqueductal gray and basolateral nucleus of amygdala the most pronounced, but
      significantly higher in comparison with C group only, expression of c-Fos was
      detected in MS rats. Interestingly, a strong and uniform enhancement of c-Fos
      expression appeared in all other brain structures examined, including cortical
      areas, indicating their sensitivity to non-direct (conditioned) aversive stimuli.
      The only significant difference in c-Fos expression between LS and MS rats found
      in LHAB points to this brain structure as selectively engaged in processing of
      the emotional-cognitive component of a painful stimulation. The reactivity of
      LHAB may be responsible for the genetically determined differences in sensitivity
      to pain.

PMID- 15489022
TI  - Regulation of cAMP levels in area CA1 of hippocampus by Gi/o-coupled receptors is
      stimulus dependent in mice.
AB  - The cAMP signaling cascade plays a critical role in regulating synaptic efficacy
      and cellular excitability in hippocampus. Adenylyl cyclase (AC) activation and
      subsequent generation of cAMP occurs through a number of mechanisms in area CA1
      of hippocampus, including Galpha(s)-mediated stimulation upon G-protein coupled
      receptor (GPCR) activation and Ca2+ -mediated stimulation upon NMDA receptor
      activation. In addition, activation of Gi/o-coupled receptor subtypes can
      regulate cAMP levels through modulation of AC activity. Multiple Gi/o-coupled
      receptor subtypes are expressed in area CA1, where they are commonly thought to
      dampen synaptic transmission and excitability, in part through inhibition of AC
      activity and cAMP generation. However, a large family of ACs exists, and in
      recombinant systems, the cAMP signals generated by these AC isoforms are both
      inhibited and enhanced by Gi/o-coupled receptors in a manner dependent on the AC
      isoform and stimulus. Thus, we have assessed the effects of activating several
      different Gi/o-coupled receptors on the generation of cAMP induced either by NMDA
      receptor activation or by beta-adrenergic receptor activation within area CA1 of
      mouse hippocampus. We find that in situ the effect of Gi/o-coupled receptor
      activation does indeed depend upon the means by which ACs are activated. In
      addition, the effects are also Gi/o-coupled receptor-specific, suggesting
      additional complexity. These data indicate that Gi/o-coupled receptors may play
      roles in "routing" second messenger signaling in area CA1.

PMID- 15489023
TI  - Hippocampal N-methyl-D-aspartate receptor-mediated encoding and retrieval
      processes in spatial working memory: delay-interposed radial maze performance in
      rats.
AB  - In order to clarify the role of hippocampal N-methyl-D-aspartate (NMDA) and alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors in different
      stages of spatial working memory, we first assessed the rats' performance in a
      delay-interposed eight-arm radial maze task (experiment 1). When a delay was
      interposed after the first four correct choices, rats showed more errors in the
      second-half performance depending on the length of delay; however, they did not
      show any significant increase of error choices until the delay was beyond 2 h. We
      then tested the effect of 2-amino-5-phosphonopentanoic acid (AP5), a competitive
      NMDA receptor antagonist, and 2,3-dioxo-6-nitro-1,2,3,4
      tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX)-disodium, an AMPA receptor
      antagonist, on a standard (no delay-interposed) radial maze task (experiment 2).
      The drug effect was maintained 15-30 min but it completely disappeared 60 min
      after dorsal hippocampal microinjection. Based on these findings we finally
      investigated the effects of hippocampal AP5 and NBQX administered at different
      stages of 2 h delay-interposed radial maze task on the second-half performance
      (experiment 3). AP5 immediately before the first-half and before the second-half
      performance significantly impaired the correct choices, but the treatment
      immediately after the first-half performance did not, while NBQX impaired them in
      all three conditions. Results suggest that hippocampal NMDA receptors play an
      important role in encoding and retrieval processes of spatial working memory,
      while AMPA receptor activation is necessary not only in these processes but also
      in consolidation/retention process.

PMID- 15489024
TI  - Role of neuronal nicotinic receptors in the effects of nicotine and ethanol on
      contextual fear conditioning.
AB  - Nicotine can enhance contextual learning while ethanol impairs some forms of
      learning. Nicotine can overcome some of the impairing effects of ethanol when the
      two drugs are co-administered. The specific brain nicotinic acetylcholine
      receptors (nAChRs) that mediate nicotine's effects on contextual learning and
      whether any of ethanol's actions are mediated by nAChRs are unknown. The
      potential roles of nAChRs in contextual and cued fear conditioning as well as the
      effects of nicotine, ethanol, or co-administration of nicotine and ethanol were
      examined in wild type and homozygous null mutant mice from alpha7, beta2, beta3,
      and beta4 mouse lines at 24 h after training. Nicotine was given prior to
      training and testing, whereas ethanol was given only before training. Nicotine
      enhanced contextual learning in both alpha7 wild types and mutants when mice were
      trained at 0.17 mA, but not 0.35 mA. Mutants lacking the alpha7 subunit were less
      sensitive to the memory impairing effects of ethanol trained at 0.35 mA. beta2
      Null mutants receiving saline showed a small, but significant, impairment in
      contextual learning compared with wild type littermates when the shock stimulus
      was 0.35 mA. Beta2 Null mutant mice also did not respond to the cognitive
      enhancing effects of nicotine alone, or after ethanol administration. beta3 and
      beta4 null mutants did not differ from wild types either after saline or any of
      drug treatments. These results show that beta2-containing nAChRs, but not beta3-
      or beta4-containing receptors, mediate the enhancing effects of nicotine on
      contextual learning and confirm previous studies implicating beta2 in other forms
      of learning. A new role for alpha7 nAChRs in regulating sensitivity to the
      cognitive disrupting effects of ethanol is proposed.

PMID- 15489025
TI  - Activation of alpha2-adrenergic receptors into the lateral parabrachial nucleus
      enhances NaCl intake in rats.
AB  - Water and NaCl intake is strongly inhibited by the activation of alpha(2)
      adrenergic receptors with clonidine or moxonidine (alpha(2)
      adrenergic/imidazoline agonists) injected peripherally or into the forebrain and
      by serotonin and cholecystokinin in the lateral parabrachial nucleus (LPBN).
      Considering that alpha(2)-adrenergic receptors exist in the LPBN and the similar
      origin of serotonergic and adrenergic afferent pathways to the LPBN, in this
      study we investigated the effects of bilateral injections of moxonidine alone or
      combined with RX 821002 (alpha(2)-adrenergic antagonist) into the LPBN on 1.8%
      NaCl and water intake induced by the treatment with s.c. furosemide
      (10mg/kg)+captopril (5 mg/kg). Additionally, we investigated if moxonidine into
      the LPBN would modify furosemide+captopril-induced c-fos expression in the
      forebrain. Male Holtzman rats with cannulas implanted bilaterally in the LPBN
      were used. Contrary to forebrain injections, bilateral LPBN injections of
      moxonidine (0.1, 0.5 and 1 nmol/0.2 microl) strongly increased
      furosemide+captopril-induced 1.8% NaCl intake (16.6+/-2.7, 44.5+/-3.2 and 44.5+/
      4.3 ml/2 h, respectively, vs. vehicle: 6.9+/-1.5 ml/2 h). Only the high dose of
      moxonidine increased water intake (23.3+/-3.8 ml/2 h, vs. vehicle: 12.1+/-2.6
      ml/2 h). Prior injections of RX 821002 (10 and 20 nmol/0.2 microl) abolished the
      effect of moxonidine (0.5 nmol) on 1.8% NaCl intake. Moxonidine into the LPBN did
      not modify furosemide+captopril-induced c-fos expression in forebrain areas
      related to the control of fluid-electrolyte balance. The results show that the
      activation of LPBN alpha(2)-adrenergic receptors enhances furosemide+captopril
      induced 1.8% NaCl and water intake. This enhancement was not related to prior
      alteration in the activity of forebrain areas as suggested by c-fos expression.
      Previous and present results indicate opposite roles for alpha(2)-adrenergic
      receptors in the control of sodium and water intake according to their
      distribution in the rat brain.

PMID- 15489026
TI  - Functional similarities and differences of AMPA and kainate receptors expressed
      by cultured rat sensory neurons.
AB  - Dorsal root ganglion neurons express functional AMPA and kainate receptors near
      their central terminals. Activation of these receptors causes a decrease in
      glutamate release during action potential evoked synaptic transmission. Due to
      differences in kinetic properties and expression patterns of these two families
      of glutamate receptors in subpopulations of sensory neurons, AMPA and kainate
      receptors are expected to function differently. We used embryonic dorsal root
      ganglion (DRG) neurons maintained in culture to compare functional properties of
      kainate and AMPA receptors. Most DRG neurons in culture expressed kainate
      receptors and about half also expressed AMPA receptors. Most AMPA and kainate
      receptor-expressing DRG neurons were sensitive to capsaicin, suggesting
      involvement of these glutamate receptors in nociception. When activated by
      kainate, AMPA receptors were capable of driving a sustained train of action
      potentials while kainate receptors tended to activate action potential firing
      more transiently. Glutamate elicited more action potentials and a larger steady
      state depolarization in neurons expressing both AMPA and kainate receptors than
      in neurons expressing only kainate receptors. Adding to their more potent
      activation properties, AMPA receptors recovered from desensitization much more
      quickly than kainate receptors. Activation of presynaptic receptors by low
      concentrations of kainate, but not ATPA, caused a tetrodotoxin-sensitive increase
      in the frequency of spontaneous EPSCs recorded in dorsal horn neurons. By
      recording synaptic pairs of DRG and dorsal horn neurons, we found that activation
      of presynaptic kainate and AMPA receptors decreased evoked glutamate release from
      terminals of DRG neurons in culture. Our data suggest that the endogenous ligand,
      glutamate, will cause a different physiological impact when activating these two
      types of non-NMDA glutamate receptors at central or peripheral nerve endings of
      sensory neurons.

PMID- 15489027
TI  - Modulation of hippocampal excitability by 5-HT4 receptor agonists persists in a
      transgenic model of Alzheimer's disease.
AB  - 5-HT(4) receptors are widely distributed in both peripheral and central nervous
      systems where they couple, via a G-protein, to the activation of adenylate
      cyclase. In the brain, the highest 5-HT(4) receptor densities are found in the
      limbic system, including the hippocampus and frontal cortex. It has been
      suggested that activation of these receptors may be of therapeutic benefit in
      diseases that produce cognitive deficits such as Alzheimer's disease (AD).
      Previous electrophysiological studies have shown that the 5-HT(4) agonist,
      Zacopride, can increase population spike amplitude recorded in region CA1 of rat
      hippocampal slices in a cyclic AMP (cAMP)/cAMP-dependent protein kinase A
      dependent manner. We report here that the 5-HT(4) agonist, Prucalopride, and the
      5-HT(4) partial agonist, SL65.0155, produce a similar effect in rat hippocampal
      slices and that the specific 5-HT(4) antagonist, GR113808, blocks these effects.
      To investigate the potential use of 5-HT(4) agonists in the treatment of AD,
      Prucalopride was applied to hippocampal slices from a transgenic mouse line that
      overexpresses the Abeta peptide. Despite the deficit in synaptic transmission
      present in these mice, the percentage increase of the CA1 population spike
      induced by Prucalopride was the same as that observed in wild-type mice. These
      data support 5-HT(4) receptors as a target for cognitive enhancement and suggest
      that a partial agonist would be sufficient to produce benefits, while reducing
      potential peripheral side effects. In addition, we show that 5-HT(4) receptors
      remain functional in the presence of excess Abeta peptide and may therefore be a
      useful target in AD.

PMID- 15489028
TI  - Enkephalinergic inhibition of raphe pallidus inputs to rat hypoglossal
      motoneurones in vitro.
AB  - Hypoglossal motoneurones play a major role in maintaining the patency of the
      upper airways and in determining airways resistance. These neurones receive
      inputs from many different regions of the neuroaxis including the caudal raphe
      nuclei. Whilst we have previously shown that glutamate is utilised in projections
      from one of these caudal raphe nuclei, the raphe pallidus, to hypoglossal
      motoneurones, these raphe pallidus-hypoglossal projections also contain multiple
      co-localised neuropeptides, including a population that are immunopositive for
      enkephalin. The role of enkephalin in the control of hypoglossal motoneurones is
      unknown. Therefore the aim of these studies was to determine whether enkephalins
      modulate caudal raphe glutamatergic inputs to hypoglossal motoneurones. Whole
      cell recordings were made from rat hypoglossal motoneurones in vitro, with
      glutamate-mediated excitatory postsynaptic currents (EPSCs) evoked in these
      neurones following electrical stimulation within the raphe pallidus. Superfusion
      of enkephalin significantly decreased the amplitude of these raphe pallidus
      evoked EPSCs (56.1+/-29% of control, P<0.001), an action that was mirrored by the
      tau-opioid receptor agonist, [D-Ala, N-Me-Phe, Gly-ol]-enkephalin acetate
      (DAMGO;53.8+/-26%, P<0.01), but not by the delta-opioid receptor agonist, [D-Pen]
      enkephalin (DPDPE). Enkephalin also increased the amplitude ratio (1.57+/-0.36
      vs. 1.14+/-0.27, P<0.01) of pairs of evoked EPSCs (paired pulse ratio), decreased
      the frequency (P<0.0001) but not the amplitude of miniature EPSCs, whilst having
      no effect on the inward current evoked by glutamate applied directly to the
      postsynaptic cell (97.8+/-2.2% of control, P=n.s.). Likewise, DAMGO also
      increased the paired pulse ratio (1.62+/-0.35 vs. 1.31+/-0.14, P<0.05) and
      decreased the frequency of miniature EPSCs (P<0.0001). Together, these data
      suggest that enkephalin acts at tau-opioid receptors located on the presynaptic
      terminals of raphe pallidus inputs to hypoglossal motoneurones to significantly
      decrease glutamate release from these projections.

PMID- 15489029
TI  - Chronic antidepressant treatment alters serotonergic regulation of GABA
      transmission in prefrontal cortical pyramidal neurons.
AB  - The serotonin system is highly involved in the pathophysiology of mood disorders
      such as depression and anxiety. Currently, the most widely used treatment for
      these illnesses is selective serotonin (5-HT)reuptake inhibitors, such as
      fluoxetine. Because of the multiplicity of 5-HT receptors and their different
      adaptive properties, the chronic effects of fluoxetine have remained unclear. In
      this study, we investigated the alteration of 5-HT functions by long-term
      antidepressant treatment in pyramidal neurons of prefrontal cortex (PFC), a brain
      region crucial for the control of emotion and cognition. One prominent function
      of serotonin in PFC is to regulate GABAergic inhibitory transmission. Application
      of 5-HT induced a large, desensitizing enhancement of the amplitude and frequency
      of spontaneous inhibitory postsynaptic currents (sIPSC), as well as a potent
      reduction of electrically evoked IPSC (eIPSC). Chronic fluoxetine treatment did
      not alter basal sIPSC, but reduced eIPSC in response to different stimulus
      strengths. Moreover, chronic (but not acute) fluoxetine treatment caused a much
      faster desensitization of the 5-HT effect on sIPSC, and significantly attenuated
      the 5-HT effect on eIPSC. Application of a 5-HT(2) receptor agonist produced
      similar effects as 5-HT on sIPSC and eIPSC, and these effects were similarly
      altered by long-term fluoxetine treatment. These electrophysiological results
      suggest that chronic antidepressant treatment resulted in a down-regulation of
      the synaptic function of forebrain 5-HT(2) receptors. Given the key role of
      GABAergic inhibitory transmission in controlling PFC functions, its altered
      regulation by serotonin after chronic fluoxetine treatment may provide a
      mechanism underlying the therapeutic action of antidepressants.

PMID- 15489030
TI  - Interleukin-12 p40-homodimer production in sensory dorsal root ganglion neurons.
AB  - Recently, the reports that sensory nerves contribute to induction and development
      of peripheral inflammation have been accumulating. Although neuropeptides have
      been thought to participate in modulation of inflammation, we supposed the
      involvement of cytokines. Interleukin-12 (IL-12) is a key regulator of cell
      mediated immunity. IL-12 is heterodimer cytokine consisting of a p35 and a p40
      subunit, but the results that some of immune cell types secrete p40-homodimer
      have been reported. In this study, we investigated the expression and secretion
      of IL-12 in mouse sensory neurons in order to evaluate the involvement of sensory
      neurons in cell-mediated immunity. Expression of IL-12 p40 mRNA was detected and
      enhanced by interferon-gamma (IFN-gamma), but another subunit of IL-12 p35 mRNA
      was not detected in sensory dorsal root ganglion (DRG) neurons in culture. IL-12
      p40 molecule was detected in DRG neurons by immunocytochemistry. In addition,
      cultured DRG neurons secreted p40-homodimer that inhibited IL-12-induced STAT4
      phosphorylation in T cells. p40 mRNA expression was accumulated in DRG after
      administration of IFN-gamma into mouse footpad, and this enhancement was
      eliminated by a cut of sciatic nerve. These results suggest the possibility that
      p40-homodimer derived from sensory nerves suppresses the excessive peripheral
      inflammation.

PMID- 15489031
TI  - Persistent subthreshold voltage-dependent cation single channels in
      suprachiasmatic nucleus neurons.
AB  - The hypothalamic suprachiasmatic nucleus (SCN) contains the primary circadian
      pacemaker in mammals, and transmits circadian signals by diurnal modulation of
      neuronal firing frequency. The ionic mechanisms underlying the circadian
      regulation of firing frequency are unknown, but may involve changes in membrane
      potential and voltage-gated ion channels. Here we describe novel tetrodotoxin-
      and nifedipine-resistant subthreshold, voltage-dependent cation (SVC) channels
      that are active at resting potential of SCN neurons and increase their open
      probability (P(o)) with membrane depolarization. The increased P(o) reflects
      changes in the kinetics of the slow component of the channel closed-time, but not
      the channel open-time or fast closed-time. This study provides a background for
      investigation of the possible role of SVC channels in regulation of circadian
      oscillations of membrane excitability in SCN neurons.

PMID- 15489032
TI  - Induction of neuropeptide gene expression and blockade of retrograde transport in
      facial motor neurons following local peripheral nerve inflammation in severe
      combined immunodeficiency and BALB/C mice.
AB  - Peripheral nerve inflammation is a common clinical problem that accompanies nerve
      injury and several diseases including Guillain-Barre syndrome and acute and
      chronic inflammatory demyelinating polyneuropathy. To determine if neuropeptides
      are induced in motor neurons after inflammation and to study the mechanisms
      involved, a nerve cuff soaked in complete Freund's adjuvant (CFA) was applied
      locally to the facial nerve of Balb/C mice. This procedure resulted in an influx
      of lymphocytes and macrophages to the affected area and a blockade of retrograde
      axonal transport distal, but not proximal, to the site of application. The same
      treatment resulted in a strong ipsilateral induction of pituitary adenylyl
      cyclase activating peptide (PACAP) gene expression in motor neurons in the facial
      motor nucleus. Because the changes could have occurred due to the loss of target
      derived factors or to the production of new factors by immune cells, we studied
      the effect of the inflammatory stimulus on PACAP mRNA in mice with severe
      combined immunodeficiency (SCID). As expected, SCID mice showed a severely
      reduced influx of T-lymphocytes but not macrophages to the peripheral nerve.
      Moreover, although retrograde transport distal to the inflammation site was
      blocked similarly in control and SCID mice, the number of motor neurons
      expressing PACAP mRNA after CFA application was significantly reduced in SCID
      mice. The data indicate that the induction of PACAP mRNA during nerve
      inflammation requires the involvement of lymphocytes. However, because the
      induction of PACAP gene expression was only partially blocked in SCID mice,
      macrophages, loss of target-derived factors, or other mechanisms may also
      contribute to the upregulation of PACAP gene expression in motor neurons after
      nerve inflammation.

PMID- 15489033
TI  - Phosphodiesterase inhibitors: a novel mechanism for receptor-independent
      antipsychotic medications.
AB  - OVERVIEW: All current antipsychotic medications work by binding to Gi-coupled
      dopamine (DA) D2 receptors. Such medications are thought to affect cellular
      function primarily by decreasing DA-mediated regulation of intracellular cyclic
      adenosine monophosphate (cAMP).However, several studies indicate that cAMP signal
      transduction abnormalities in schizophrenia may not be limited to D2-containing
      cells. The current study examines the potential of using non-receptor-based
      agents that modify intracellular signal transduction as potential antipsychotic
      medications. METHODS: The indirect DA agonist amphetamine has been used to model
      the auditory sensory processing deficits in schizophrenia. Such pharmacologically
      induced abnormalities are reversed by current antipsychotic treatments. This
      study examines the ability of the phosphodiesterase-4 inhibitor, rolipram, to
      reverse amphetamine-induced abnormalities in auditory-evoked potentials that are
      characteristic of schizophrenia. RESULTS: Rolipram reverses amphetamine-induced
      reductions in auditory-evoked potentials. CONCLUSION: This finding could lead to
      novel approaches to receptor-independent treatments for schizophrenia.

PMID- 15489034
TI  - Wide range of lineages of cells expressing nerve growth factor mRNA in the nerve
      lesions of patients with vasculitic neuropathy: an implication of endoneurial
      macrophage for nerve regeneration.
AB  - In situ localization of nerve growth factor (NGF) mRNA was examined in the nerve
      lesions of patients with vasculitic neuropathy. Double labeling of in situ
      hybridization for NGF mRNA and immunohistochemistry for cell markers showed that
      NGF mRNA was expressed in a wide range of lineages of cells: Schwann cells,
      infiltrating macrophages, T cells and perivascular cells. Round-shaped
      macrophages with early-phase features expressed high levels of NGF mRNA, in
      contrast to late-phase polymorphic macrophages, which expressed low levels of NGF
      mRNA. NGF mRNA was also expressed universally in T cells with various cell
      surface markers. Epineurial macrophages surrounding vasculitic lesions and
      endoneurial T cells expressed high levels of NGF mRNA in the damaged nerves.
      Moreover, the extent of endoneurial NGF expression level in macrophages was
      closely related to the degree of axonal regeneration. These results suggest that
      NGF is expressed in a wide range of lineages of cells but is differentially
      expressed spatially in vasculitic nerve lesions, and that the expressed NGF,
      particularly in macrophages, may play an important role in the nerve regeneration
      process.

PMID- 15489035
TI  - Growth hormone treatment attenuates age-related changes in hippocampal short-term
      plasticity and spatial learning.
AB  - Downregulation of the growth hormone/insulin-like growth factor-1 (IGF-1)axis is
      one of the most robust biomarkers of mammalian aging. Reports have suggested that
      age-related changes in secretion of growth hormone and IGF-1 contribute to the
      development of some peripheral characteristics of the aged phenotype including
      decreased bone density and lean body mass. Recent work has focused on the
      identification of a role for age-related reductions in growth hormone and IGF-1
      in the development of cognitive impairments associated with aging. In the current
      study, we report that aged (30 month-old) Brown Norway x Fisher rats demonstrate
      impairments in spatial learning compared with adult (10 month-old) animals, and
      that 4-month treatment with growth hormone (300 microg twice daily) attenuates
      age-related learning impairments. After 6 months of treatment, we employed an
      extracellular paired-pulse protocol to investigate age-related changes in
      hippocampal short-term plasticity, and found that aged rats exhibit significantly
      increased paired-pulse ratios (PPRs) at an interpulse interval of 50 ms compared
      with adult rats. Long-term growth hormone administration restored PPRs in aged
      animals to values comparable to those observed in adult controls. Since the age
      related changes observed in PPR may result from decreases in hippocampal
      inhibitory tone mediated by GABA(A) receptors, we assessed GABA(A) receptor
      subunit expression by immunoblot analysis. Data revealed significant age-related
      decreases in GABA(A) receptor alpha-1 subunit expression which were attenuated by
      growth hormone treatment. However, hippocampal levels of the gamma2 subunit,
      glutamic acid decarboxylase (GAD)(65), and GAD(67) protein concentrations were
      not significantly affected by age or growth hormone treatment. In conclusion, we
      suggest that age-related decreases in growth hormone and IGF-1 contribute to
      cognitive decline, in part, via alterations in hippocampal short-term plasticity.
      Changes in plasticity may reflect a shift in the balance of hippocampal
      inhibitory and excitatory function.

PMID- 15489036
TI  - Induced depressive behavior impairs learning and memory in rats.
AB  - While it is generally accepted that cognitive processes such as learning and
      memory are affected by emotion, the impact of depression on learning and memory
      has rarely been directly studied in experimental animals. Effects of induced
      depressive behavior on learning and memory were determined in rats, using an open
      space swim test, a novel animal model of depressive behavior that is developed
      recently in our laboratory. The model indexes searching activity of the animals,
      with the induced depressive immobility behavior showing specific sensitivity to
      three major prototypic classes of antidepressants and a selective serotonin
      reuptake inhibitor. The induced depressive behavior in rats showed a delayed
      response to chronic antidepressant treatment and had a lasting effect on the
      ability of rats to learn and recall the learned experience. It impaired the
      subsequent ability of rats to learn and recall both a spatial water maze task and
      a multi-trial passive avoidance task. These impairments were all sensitive to
      antidepressant therapeutics, but not to buspirone, an anxiolytic. By way of
      contrast, the ability of the rats to sense and move to a visible platform and to
      escape from an unconditioned shock stimulus was neither impaired by inducing the
      depressive behavior nor altered by the drug treatment, suggesting that non
      specific changes in sensorimotor ability were not involved. These impairments of
      learning and memory indicate that the depressive behavior-induced deficits show
      generalizability and are not context-limited. This animal model of depressive
      behavior shows promising potential as a screen for novel antidepressive
      therapeutics and as a disease model for revealing network/cellular/molecular
      mechanisms in the pathophysiology of depression and depression-induced cognitive
      deficits.

PMID- 15489037
TI  - Effects of sensorimotor restriction and anoxia on gait and motor cortex
      organization: implications for a rodent model of cerebral palsy.
AB  - Chronic or acute perinatal asphyxia (PA) has been correlated with the subsequent
      development of cerebral palsy (CP), a developmental neurological disorder
      characterized by spasticity and motor abnormalities often associated with
      cognitive deficits. Despite the prevalence of CP, an animal model that mimics the
      lifetime hypertonic motor deficits is still not available. In the present study,
      the consequences of PA on motor behavior, gait and organization of the primary
      motor cortex were examined in rats, and compared with the behavioral and
      neurological consequences of early postnatal movement-restriction with or without
      oxygen deprivation. Rats subjected to PA had mild increases in muscular tone
      accompanied by subtle differences in walking patterns, paralleled by
      significantly altered but relatively modest disorganization of their primary
      motor cortices. Movement-restricted rats, suffering PA or not, had reduced body
      growth rate, markedly increased muscular tone at rest and with active flexion and
      extension around movement-restricted joints that resulted in abnormal walking
      patterns and in a profoundly distorted representation of the hind limbs in the
      primary motor cortex. Within the sensorimotor-restricted groups, non-anoxic rats
      presented the most abnormal pattern and the greatest cortical representational
      degradation. This outcome further supports the argument that PA per se may
      represent a substrate for subtle altered motor behaviors, and that PA alone is
      sufficient to alter the organization of the primary motor cortex. At the same
      time, they also show that early experience-dependent movements play a crucial
      role in shaping normal behavioral motor abilities, and can make a powerful
      contribution to the genesis of aberrant movement abilities.

PMID- 15489038
TI  - Differential contribution of dopamine D2S and D2L receptors in the modulation of
      glutamate and GABA transmission in the striatum.
AB  - Compelling evidence indicates that the long (D2L) and the short (D2S) isoform of
      dopamine (DA) D2 receptors serve distinct physiological functions in vivo. To
      address the involvement of these isoforms in the control of synaptic transmission
      in the striatum, we measured the sensitivity to D2 receptor stimulation of
      glutamate- and GABA-mediated currents recorded from striatal neurons of three
      mutant mice, in which the expression of D2L and D2S receptors was either ablated
      or variably altered. Our data indicate that both isoforms participate in the
      presynaptic inhibition of GABA transmission in the striatum, while the D2
      receptor-dependent modulation of glutamate release preferentially involves the
      D2S receptor. Accordingly, the inhibitory effects of the DA D2 receptor agonist
      quinpirole (10 microM) on GABA(A)-mediated spontaneous inhibitory postsynaptic
      currents (IPSCs)correlate with the total number of D2 receptor sites in the
      striatum, irrespective of the specific receptor isoform expressed. In contrast,
      glutamate-mediated spontaneous excitatory postsynaptic currents (EPSCs) were
      significantly inhibited by quinpirole only when the total number of D2 receptor
      sites, normally composed by both D2L and D2S receptors in a ratio favoring the
      D2L isoform, was modified to express only the D2S isoform at higher than normal
      levels. Understanding the physiological roles of DA D2 receptors in the striatum
      is essential for the treatment of several neuropsychiatric conditions, such as
      Parkinson's disease, Tourette's syndrome, schizophrenia, and drug addiction.

PMID- 15489039
TI  - Northern blot and in situ hybridization analyses for the development of
      myristoylated alanine-rich c-kinase substrate mRNA in the monkey cerebral cortex.
AB  - Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major neuron-specific
      substrate for protein kinase C, and is involved in both neurite outgrowth and
      synaptic plasticity. Using both Northern blot and in situ hybridization
      techniques, we investigated whether the expression of MARCKS mRNA in the monkey
      cerebral neocortex and hippocampus changed during the developmental period. In
      each of four neocortical areas examined, i.e. the prefrontal area (area FD of
      [Illinois Monographs in the Medical Sciences (1947) 1]), the temporal association
      area (TE), the primary somatosensory area (PB), and the primary visual area (OC),
      the Northern blot analysis showed that the amount of MARCKS mRNA was high during
      the fetal and early postnatal periods, and decreased sharply between postnatal
      day 70 and postnatal month 6. The in situ hybridization experiments showed that
      the expression of MARCKS mRNA was decreased in every layer of neocortical areas
      at postnatal month 6 or later. In the primary sensory areas (areas PB and OC),
      the degree of decrease was higher in the supragranular layers (layers II and III)
      than in the infragranular layers (layers V and VI). In the hippocampus, the
      developmental change in the amount of MARCKS mRNA was small, but the in situ
      hybridization revealed a prominent decrease in Ammon's horn in monkeys on
      postnatal month 8 and later. These findings indicate that region-specific
      expression of MARCKS mRNA is established around postnatal month 6. We suggest
      that the extensive expression of MARCKS mRNA is one of the molecular bases of
      high plasticity in the infant cerebral cortex.

PMID- 15489040
TI  - A voltage-gated potassium channel, Kv3.1b, is expressed by a subpopulation of
      large pyramidal neurons in layer 5 of the macaque monkey cortex.
AB  - In the cerebral cortex, the voltage-gated potassium channel, Kv3.1b, a splicing
      variant of Kv3.1, has been associated with fast-firing interneurons. Here, we
      report strong expression of Kv3.1b-protein and mRNA in both Betz and Meynert
      pyramidal cells of the monkey, as shown by immunohistochemistry and in situ
      hybridization. Strong expression also occurs in large pyramidal neurons in layer
      5 of several cortical areas. In addition, most of these Betz and layer 5
      pyramids, and about 10% of the labeled Meynert cells weakly co-expressed the
      calcium binding protein parvalbumin. Electron microscopy shows that the
      expression of Kv3.1b is localized to the somal and proximal dendritic cytoplasmic
      membrane, as expected for a channel protein. These results suggest that some
      large pyramidal neurons may constitute a functional subpopulation, with a
      distinctive distribution of voltage-gated potassium channels capable of
      influencing their repetitive firing properties.

PMID- 15489041
TI  - 17beta-estradiol pretreatment reduces CA1 sector cell death and the spontaneous
      hyperthermia that follows forebrain ischemia in the gerbil.
AB  - Pretreatment with 17beta-estradiol attenuates ischemia-induced hippocampal cornu
      ammonis 1 (CA1) neuronal death. We assessed whether this is mediated through
      prevention of hyperthermia that normally follows ischemia in gerbils. Male
      gerbils were given sustained-released 17beta-estradiol pellets or sham operation.
      Later, a guide cannula was implanted for brain temperature measurement and some
      were implanted with core temperature telemetry probes. Gerbils were subjected to
      either 5 min bilateral carotid artery occlusion or sham procedures 2 weeks after
      pellet surgery. Brain temperature was normothermic during surgery in all cases.
      In experiment 1, only core temperature was measured afterward in untreated and
      estrogen-treated gerbils. In experiment 2, postischemic core temperature was
      measured in untreated and two estrogen-treated ischemic groups, one of which had
      their postischemic temperature increased, via infrared lamp, to mimic the
      untreated group. Habituation was assessed on days 5 and 6. Hyperthermia, like
      that which occurs spontaneously, was forced on untreated and estrogen-treated
      ischemic animals in the third experiment, where brain temperature was measured.
      CA1 cell counts were assessed after a 7-day survival. A fourth experiment
      measured brain and core temperature simultaneously in normal gerbils during
      heating with an infrared lamp. Estrogen did not affect core temperature of non
      ischemic gerbils whereas spontaneous postischemic hyperthermia was blocked.
      Estrogen reduced cell death and provided behavioral protection when gerbils
      regulated their own core temperature, but not when core hyperthermia was
      enforced. Conversely, estrogen reduced cell death in gerbils that had their brain
      temperature elevated. Experiment 4 showed that the brain becomes overheated (by
      approximately 1 degree C) when core temperature is elevated. Accordingly,
      estrogen likely failed to reduce CA1 injury in experiment 2, when core
      hyperthermia was enforced, because of overheating the brain. In conclusion,
      estrogen reduces CA1 cell death by mechanisms other than preventing hyperthermia.
      Our results also suggest that future studies regulate brain instead of body
      temperature.

PMID- 15489042
TI  - Testosterone modulation of seizure susceptibility is mediated by neurosteroids
      3alpha-androstanediol and 17beta-estradiol.
AB  - Testosterone modulates seizure susceptibility in animals and humans, but the
      underlying mechanisms are obscure. Here, testosterone modulation of seizure
      susceptibility is hypothesized to occur through its conversion to neurosteroids
      with "anticonvulsant" and "proconvulsant" actions, and hence the net effect of
      testosterone on neural excitability and seizure activity depends on the levels of
      distinct testosterone metabolites. Testosterone undergoes metabolism to
      neurosteroids via two distinct pathways. Aromatization of the A-ring converts
      testosterone into 17beta-estradiol. Reduction of testosterone by 5alpha-reductase
      generates 5alpha-dihydrotestosterone (DHT), which is then converted to 3alpha
      androstanediol (3alpha-Diol), a powerful GABA(A) receptor-modulating neurosteroid
      with anticonvulsant properties. Systemic doses of testosterone decreased seizure
      threshold in rats and increased the incidence and severity of pentylenetetrazol
      (PTZ)-induced seizures in mice. These proconvulsant effects of testosterone were
      associated with increases in plasma 17beta-estradiol and 3alpha-Diol
      concentrations. Pretreatment with letrozole, an aromatase inhibitor that blocks
      the conversion of testosterone to 17beta-estradiol, significantly inhibited
      testosterone-induced exacerbation of seizures. The 5alpha-reductase inhibitor
      finasteride significantly reduced 3alpha-Diol levels and also blocked letrozole's
      ability to inhibit the proconvulsant effects of testosterone. The 5alpha-reduced
      metabolites of testosterone, DHT and 3alpha-Diol, had powerful anticonvulsant
      activity in the PTZ test. Letrozole or finasteride had no effect on seizure
      protection by DHT and 3alpha-Diol, but indomethacin partially reversed DHT
      actions. 3alpha-Diol but not 3beta-androstanediol, a GABA(A) receptor-inactive
      stereoisomer, suppressed 4-aminopyridine-induced spontaneous epileptiform
      bursting in rat hippocampal slices. Thus, testosterone-derived neurosteroids
      3alpha-Diol and 17beta-estradiol could contribute to the net cellular actions of
      testosterone on neural excitability and seizure susceptibility.

PMID- 15489043
TI  - Characterization and function of TWIK-related acid sensing K+ channels in a rat
      nociceptive cell.
AB  - We examined the properties of a proton sensitive current in acutely dissociated,
      capsaicin insensitive nociceptive neurons from rat dorsal root ganglion (DRG).
      The current had features consistent with K(+) leak currents of the KCNK family
      (TASK-1, TASK-3; TWIK-related acid sensing K(+)). Acidity and alkalinity induced
      inward and outward shifts in the holding current accompanied by increased and
      decreased whole cell resistance consistent with a K(+) current. We used alkaline
      solutions to open the channel and examine its properties. Alkaline evoked
      currents (AECs; pH 10.0-10.75), reversed near the K(+) equilibrium potential (-74
      mV), and were suppressed 85% in 0 mM K(+). AECs were insensitive to Cs(+) (1 mM)
      and anandamide (1 microM), but blocked by Ba(++) (1 mM), quinidine (100 microM)
      or Ruthenium Red (10 microM). This pharmacology was identical to that of rat TASK
      3 and inconsistent with that of TASK-1 or TASK-2. The TASK-like AEC was not
      modulated by PKA (forskolin, kappa opioid agonists U69593 and GR8696,
      somatostatin) but was inhibited by PKC activator phorbol-12-myristate-13 acetate
      (PMA). When acidic solutions were used, we were able to isolate a Ba(++) and
      Ruthenium Red insensitive current that was inhibited by Zn(++). This Zn(++)
      sensitive component of the proton sensitive current was consistent with TASK-1.
      In current clamp studies, acidic pH produced sensitive changes in resting
      membrane potential but did not influence excitability (pH 7.2-6.8). In contrast,
      Zn(++) produced substantial changes in excitability at physiological pH. Alkaline
      solutions produced hyperpolarization followed by proportional burst discharges
      (pH 10.75-11.5) and increased excitability (at pH 7.4). In conclusion, multiple
      TASK currents were present in a DRG nociceptor and differentially contributed to
      distinct discharge mechanisms.

PMID- 15489044
TI  - Expression and distribution of mu opioid receptors in the inner ear of the rat.
AB  - Opioid peptides have demonstrated modulatory effects on the vestibular afferent
      discharge and are putative vestibular efferent neuromodulators. The distribution
      of their receptors in the mammalian vestibular epithelia is not known. We used
      reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization,
      Western blots and immunohistochemistry to study the expression of mu opioid
      receptor (MOR) in the Scarpa's ganglia and cristae ampullares of rats. MOR
      transcript was only detected in the somata of the vestibular afferent neurons.
      MOR-like immunoreactivity was observed in the somata of vestibular afferents and
      in nerve terminals in the cristae ampullares epithelia both in the center and
      peripheral regions. Double labeling of cristae sections with the MOR1 antibody in
      combination with antibodies against calretinin (a marker for vestibular afferents
      terminating in calices) and peripherin (a marker for afferents terminating in
      boutons), respectively showed that MOR1 immunoreactivity was in calyx, dimorphic
      and bouton vestibular afferents. MOR immunoreactivity was not detected in
      vestibular efferent fibers identified with choline acetyltransferase
      immunohistochemistry. These results indicate that MOR may mediate effects of
      vestibular efferents on afferents.

PMID- 15489045
TI  - Action of kappa and Delta opioid agonists on premotor cardiac vagal neurons in
      the nucleus ambiguus.
AB  - Both enkephalin and dynorphin containing fibers are in close proximity to neurons
      in the nucleus ambiguus, including cardiac vagal neurons. Microinjection of Delta
      and kappa agonists into the nucleus ambiguus have been shown to evoke decreases
      in heart rate. Yet little is known about the mechanisms by which Delta and kappa
      opioid receptors alter the activity of cardiac vagal neurons. This study tests
      whether kappa and Delta opioid agonists can alter the activity of cardiac vagal
      neurons by modulating likely opioid targets including voltage gated calcium
      currents, and both glycinergic and GABA) neurotransmission to cardiac vagal
      neurons. Cardiac vagal neurons were identified in vitro by a fluorescent tracer
      and studied using patch clamp techniques. Neither the kappa agonist spiradoline
      or the Delta agonist [D-Pen(2), D-Pen(5)]enkephalin (DPDPE) modulated the voltage
      gated calcium currents in cardiac vagal neurons. DPDPE also did not alter either
      glycinergic or GABAergic synaptic neurotransmission. Spiradoline did not change
      GABAergic synaptic inputs, but did significantly inhibit glycinergic synaptic
      inputs to cardiac vagal neurons. At a concentration of 1 microM, spiradoline
      inhibited the amplitude of glycinergic events, and at a concentration of 5
      microM, spiradoline inhibited both glycinergic amplitude and frequency.
      Spiradoline also inhibited both the amplitude and frequency of glycinergic
      miniature inhibitory post-synaptic currents, indicating kappa agonists likely act
      at both presynaptic and postsynaptic sites to inhibit glycinergic
      neurotransmission to cardiac vagal neurons.

PMID- 15489046
TI  - Estradiol increases delayed, N-methyl-D-aspartate receptor-mediated excitation in
      the hippocampal CA1 region.
AB  - Hippocampal functions, e.g. synaptic plasticity and hippocampal-dependent
      behavior, are influenced by the circulating levels of ovarian steroids in adult,
      female rats. The mechanisms underlying this estradiol-dependent modulation,
      however, are poorly understood. One possibility is that estradiol alters N-methyl
      D-aspartate (NMDA)-receptor functioning in the hippocampus. Here, using the in
      vitro hippocampal slice preparation, we evaluate estradiol-dependent changes in
      the NMDA receptor- and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid receptor-mediated components of excitatory postsynaptic potentials (EPSPs)
      evoked in CA1 by Schaffer collateral test stimulation. Using established
      experimental conditions [J Neurosci 17 (1997) 1848], we replicate the observation
      that estradiol pretreatment of ovariectomized rats increases a pharmacologically
      isolated NMDA receptor-mediated EPSP evoked by Schaffer collateral stimulation.
      However, using different conditions that optimize study of this evoked response,
      the estradiol-dependent increase in the monosynaptic NMDA receptor-mediated EPSP
      is eliminated. Low-intensity test stimulation of the Schaffer collaterals in this
      optimized medium reveals a novel, late NMDA receptor-mediated EPSP in CA1 from
      estradiol-pretreated rats. The mechanism(s) underlying this estradiol-dependent
      increase in a late, NMDA receptor-mediated EPSP is not known, but enhanced CA1
      CA1 excitatory circuitry and glutamate spillover could contribute to this
      response. We conclude that estradiol pretreatment enhances NMDA receptor function
      in the female hippocampus by increasing not the monosynaptic, but rather a late
      NMDA receptor-mediated response. Variations in the magnitude of this late
      response may well contribute to ovarian steroid-dependent modulation of
      hippocampal synaptic plasticity.

PMID- 15489047
TI  - Synaptic activation patterns of the perirhinal-entorhinal inter-connections.
AB  - Ample neuropsychological evidence supports the role of rhinal cortices in memory.
      The perirhinal cortex (PRC) represents one of the main conduits for the bi
      directional flow of information between the entorhinal-hippocampal network and
      the cortical mantle, a process essential in memory formation. However, despite
      anatomical evidence for a robust reciprocal connectivity between the perirhinal
      and entorhinal cortices, neurophysiological understanding of this circuitry is
      lacking. We now present the results of a series of electrophysiological
      experiments in rats that demonstrate robust synaptic activation patterns of the
      perirhinal-entorhinal inter-connections. First, using silicon multi-electrode
      arrays placed under visual guidance in vivo we performed current source density
      (CSD) analysis of lateral entorhinal cortex (LEC) responses to PRC stimulation,
      which demonstrated a current sink in layers II-III of the LEC with a latency
      consistent with monosynaptic activation. To further substantiate and extend this
      conclusion, we developed a PRC-LEC slice preparation where CSD analysis also
      revealed a current sink in superficial LEC layers in response to PRC stimulation.
      Importantly, intracellular recording of superficial LEC layer neurons confirmed
      that they receive a major monosynaptic excitatory input from the PRC. Finally,
      CSD analysis of the LEC to PRC projection in vivo also allowed us to document
      robust feedback synaptic activation of PRC neurons to deep LEC layer activation.
      We conclude that a clear bidirectional pattern of synaptic interactions exists
      between the PRC and LEC that would support a dynamic flow of information
      subserving memory function in the temporal lobe.

PMID- 15489048
TI  - Stem cell therapy for urinary stress incontinence.

PMID- 15489049
TI  - Aging in a very short-lived nematode.
AB  - Aging has been characterised in detail in relatively few animal species. Here we
      describe the aging process in free-living adults of the parasitic nematode
      Strongyloides ratti. We find that the phenomenology of aging in S. ratti free
      living females, resembles that of the short-lived free-living nematode
      Caenorhabditis elegans, except that it unfolds far more rapidly. The mean (3.0 +/
      0.1 days) and maximum (4.5 +/- 0.8 days) lifespans of free-living S. ratti
      females are approximately one quarter of equivalent values for C. elegans.
      Demographic senescence (a hallmark of aging) was observed in free-living S.
      ratti, with a mortality rate doubling time of 0.8 +/- 0.1 days (females),
      compared with 2.0 +/- 0.3 in C. elegans. S. ratti lifetime fertility and lifespan
      were affected by temperature, and there is an age-related decline in feeding rate
      and movement, similar to C. elegans, but occurring more quickly. Gut
      autofluorescence (lipofuscin) also increased with age in S. ratti free-living
      females, as in aging C. elegans. These findings show that the extreme brevity of
      life in free-living S. ratti adults, the shortest-lived nematode described to
      date, is the consequence of rapid aging, rather than some other, more rapid and
      catastrophic life-shortening pathology.

PMID- 15489050
TI  - Effects of long-term ovariectomy and estrogen treatment on maze learning in aged
      mice.
AB  - Spatial memory deficits occur earlier in female than male rodents as the animals
      age, and the cessation of estrous cycle has been suggested to play a role in this
      phenomenon. We examined the effects of long-term ovariectomy (OVX) and estrogen
      replacement therapy (ERT) with subcutaneous 17beta-estradiol minipellets on maze
      learning in aged (24-month-old) female C57BL/6J mice using a win-stay task (1/8
      arms baited) in the radial arm maze (RAM) and a position discrimination task in
      the T-maze. ERT was started 40 days before the behavioral tests both in gonadally
      intact (sham-operated) and OVX mice. The effect of early OVX on RAM performance
      was investigated using three different age groups (7, 11 and 24 months) with
      different OVX durations (4, 8 and 19 months, respectively). ERT reduced the
      number of reference memory errors in RAM in aged sham-operated and OVX mice, but
      unlike in young mice (Heikkinen et al., 2002) it had no effect on working memory
      errors. Furthermore, OVX impaired the performance of aged mice in the T-maze.
      Comparison across the three age groups and three OVX durations indicated that the
      memory impairment induced by an early age OVX attenuates as the mice get close to
      their estropausal age.

PMID- 15489051
TI  - Mucosal and systemic immunity to intestinal reovirus infection in aged mice.
AB  - Systemic immunity is progressively impaired in aging, predisposing to morbidity
      and mortality from neoplasia and infectious disease. However, the effect of aging
      on mucosal immunity is controversial. To assess intestinal immunity in aging,
      young and aged mice were orally exposed to reovirus or cholera toxin (CT) and
      specific antibody and reovirus-specific cytotoxic T-cell (CTL) responses were
      assessed. As previously reported, aged mice immunized orally with CT mounted
      diminished intestinal IgA responses to CT compared to young mice. In contrast,
      aged mice yielded two to three-fold more reovirus-specific IgA-producing cells in
      the Peyers's patches (PP) compared to young mice, and higher titers of reovirus
      specific IgA in fragment culture supernatants. Cytotoxicity and CTL frequencies
      from aged mice were not different from those of young mice. Together, these
      results suggest a diminished potential for systemic and intestinal immunity to
      orally applied protein antigens in aging, but an intact ability to respond to
      intestinal virus infection. Infection with a replicating virus may induce
      inflammatory mediators and innate immune factors that potentiate the priming of
      mucosal immunity; overcoming aging related deficits otherwise observed following
      oral immunization with non-replicating antigens, and suggests the importance of
      antigen replication to antigen-specific immunotherapy strategies in the elderly.

PMID- 15489052
TI  - Sexual dimorphism in lipid metabolic phenotype associated with old age in Sprague
      Dawley rats.
AB  - PURPOSE: Aged male rats show a decrease in liver PPARalpha. We aimed to determine
      if the sexual dimorphism in lipid metabolism observed in the PPARalpha-/- mouse
      is also present in senescent rats. RESULTS: Eighteen-month old rats were obese
      and presented high plasma NEFA concentrations. Old male rats were more
      hypercholesterolemic and hyperleptinemic than females, presenting a higher
      content in hepatic triglycerides and cholesteryl esters, while 18-month old
      females were more hypertriglyceridemic than males. Although PPARalpha expression
      and binding activity was reduced in liver from old male and female rats, the mRNA
      for a PPARalpha target gene, such as CPT-I, was reduced in old males (-56%),
      while increased by 286% in old females. LXRalpha protein was increased, and its
      binding activity was decreased in livers of old males, while livers of old
      females showed an increase in DGAT1 (2.6-fold) and DGAT2 (4.9-fold) mRNA, with
      respect to 3-month old animals. The increases in DGAT1 and DGAT2 mRNAs matched in
      old females those of plasma (3.1-fold) and liver triglycerides (5.0-fold).
      CONCLUSIONS: These features disclose a marked sexual dimorphism in lipid
      metabolism associated to old age in rats that can be partially attributed not
      only to an age-related decrease in liver PPARalpha expression, but also to
      changes in other hepatic transcription factors and enzymes, such as liver X
      receptor alpha (LXRalpha) and diacylglycerol acyltransferases (DGAT).

PMID- 15489053
TI  - Cardioprotection with cariporide, a sodium-proton exchanger inhibitor, after
      prolonged ischemia and reperfusion in senescent rats.
AB  - This study investigated the effects of cariporide, an inhibitor of sodium-proton
      exchanger (NHE), during myocardial ischemia and reperfusion in senescence.
      Isolated Langendorff perfused hearts from 4 (adult) and 24 (senescent) month old
      male Wistar rats were submitted to prolonged low-flow ischemia (LFI) at 15% of
      initial coronary flow (180 min) or to 45 min of LFI (15% of initial coronary
      flow) followed by 30 min of reperfusion, without or with cariporide (10(-6)M). In
      senescent hearts, but not in adults, treatment with cariporide during prolonged
      LFI attenuated the elevation of coronary resistances (578 +/- 84 vs 1020 +/- 129%
      of baseline value after 180 min, P < 0.05) and delayed the decrease in active
      tension (35.6 +/- 5.1 vs 22.2 +/- 3.4% of baseline value after 60 min; P < 0.05).
      During reperfusion following LFI, the coronary flow impairment was more
      pronounced in senescents than in adults (48.4 +/- 9.4 and 75.3 +/- 4.9% of
      baseline value, respectively; P < 0.05) but was fully prevented in senescent
      hearts by cariporide treatment (95.6 +/- 17.0% of baseline value; P < 0.05 vs
      untreated group). This beneficial effect of cariporide on coronary tone was
      associated with an improvement of active and resting tensions and lower LDH
      release. Such functional protective effects of cariporide suggest an operative
      NHE during LFI at both coronary and myocardial levels in senescent heart. In
      addition, cariporide-associated improvement of post-ischemic recovery of coronary
      and contractile function as well as the limitation of cellular injury suggests a
      major role of calcium overload via NHE activation during reperfusion of senescent
      ischemic heart.

PMID- 15489054
TI  - Glucocorticoid excess induces a prolonged leucine resistance on muscle protein
      synthesis in old rats.
AB  - This experiment was undertaken to examine leucine responsiveness of muscle
      protein synthesis during dexamethasone treatment and the subsequent recovery in
      young (4-5 weeks), adult (10-11 months) and old rats (21-22 months). Rats
      received dexamethasone in their drinking water. The dose and length of the
      treatment was adapted in order to generate the same muscle atrophy. Protein
      synthesis was assessed in vitro by incorporation of radiolabelled phenylalanine
      into proteins at the end of the treatment and after 3 or 7-day recovery. Results
      showed that dexamethasone did not alter muscle protein synthesis stimulation by
      leucine in young rats. In contrast, muscles from adult and old rats became
      totally resistant to leucine. Furthermore, the recovery of leucine responsiveness
      after dexamethasone withdrawal was slowed down in old rats when compared to
      younger rats. We concluded that glucocorticoids exert their catabolic action in
      adult and old rats partly through antagonising the stimulatory effect of leucine
      and may contribute to sarcopenia in old rats.

PMID- 15489055
TI  - Effect of dietary restriction and N-acetylcysteine supplementation on intestinal
      mucosa and liver mitochondrial redox status and function in aged rats.
AB  - The age-related changes of glutathione (GSH) levels and the effect of hypocaloric
      regimen and N-acetylcysteine (NAC) supplementation were investigated in
      intestinal mucosa and liver mitochondria of 28 months rats. Old rats exhibited
      lower proteins, GSH and protein sulphydrils (PSH) concentrations, higher GSH
      peroxidase (GSH-Px) activity and protein carbonyl deposit, partial inhibition of
      succinate stimulated mitochondrial state III respiration and decreased
      mitochondrial nitrosothiols (RSNO) concentration. Lower electric potential and
      current intensity were found in the colonic mucosa. Old rats undergone
      hypocaloric regimen showed higher intestinal concentrations of GSH, lower
      oxidized protein accumulation and GSH-Px activity and higher mitochondrial RSNO
      levels. Mitochondrial state III respiration and intestinal transport were
      improved. NAC supplementation enhanced GSH and PSH levels in the ileal but not in
      the colonic mucosa, GSH and RSNO in liver mitochondria, while GSH-Px and protein
      carbonyls were decreased everywhere. Mitochondrial respiration ameliorated. In
      conclusion, ageing is characterized by a spread decrease of GSH concentrations,
      increased protein oxidation and decreased mitochondrial NO content. Hypocaloric
      diet ameliorated intestinal transport and, as well as NAC, was effective in
      enhancing GSH levels but at different extent according to the investigated
      districts. Both interventions reduced the age-associated increase of GSH-Px and
      protein carbonyls and improved mitochondrial respiration.

PMID- 15489056
TI  - Effects of life-long exercise on circulating free fatty acids and muscle
      triglyceride content in ageing rats.
AB  - Regular physical exercise has emerged, together with dietary restriction, as an
      effective intervention in delaying degenerative diseases and augmenting life span
      in rodents. The mechanisms involved remain largely unknown, although a beneficial
      influence on the age-related alteration of insulin sensitivity has been
      hypothesized. As muscle triglyceride (TG) accumulation is considered a reliable
      index of muscle insulin resistance, in this study we explored muscle TG content
      in 23-month-old male Sprague-Dawley rats subjected to life-long training. Plasma
      glucose, insulin, free fatty acid (FFA) and leptin levels were also measured.
      Both voluntary running in wheels (RW) and forced training in treadmill (TM) were
      studied. As RW rats weighed less than controls, a cohort of untrained animals,
      fed to pair weight (PW) with RW, was added to discriminate the effect of exercise
      from that of food restriction. Sedentary ad libitum fed rats served as controls.
      In 23-month-old RW rats, muscle TG content was reduced by 50% with respect to age
      matched sedentary controls, while in TM group this reduction was smaller but
      still highly significant, and occurred independently on the changes in body fat
      mass. In both the trained rat groups, there was a significant decrease in
      circulating FFA levels and a trend to reduced insulin levels. In PW rats, muscle
      TG levels decreased similarly to RW rats, while plasma parameters were less
      modified. In particular, RW training was more effective than PW in preventing the
      age-related increase in circulating leptin levels. Our results suggest that
      voluntary exercise effectively counteracts the development of insulin resistance
      in the muscles of ageing rats as well as other related changes such as
      hyperlipacidaemia and compensatory hyperleptinaemia. Forced training or moderate
      food restriction appear slightly less effective than voluntary exercise in
      preventing age-dependent alterations in nutrient distribution and/or utilization.

PMID- 15489057
TI  - Effect of aging on liver functions-an experimental study in a perfused rat liver
      model.
AB  - BACKGROUND: Aging is associated with marked changes in the physiology of many
      organs. Aging of the liver has been little studied and findings are inconclusive.
      The purpose of this work was to determine the effect of aging on transport and
      metabolic functions of the liver as assessed by extraction ratio of indocyanine
      green (ICG) and urea flux respectively. Bile flow was also recorded. As ICG is
      removed exclusively by the liver without bioconversion, its clearance reflects
      hepatic functional mass. METHODS: Livers from adult (3-month old) or old (24
      month old) rats were perfused in a recirculating system for 90 min. At time 30
      min, a bolus of 0.125 mg of indocyanine green was introduced in the perfusion
      buffer. At least every 10 minutes, the perfusion buffer was sampled for the
      measurements of ICG and urea. Bile flow was closely monitored throughout the
      experiment. RESULTS: Extraction ratio of ICG was increased in livers from old
      rats (9.49 +/- 2.84 vs 3.70 +/- 1.56% of ICG extracted), whereas urea flux was
      diminished (0.33 +/- 0.06 vs 1.33 +/- 0.65 micromol/min/% of ICG extracted) and
      bile flow was unchanged (4.03 +/- 1.02 vs 3.57 +/- 1.34 microl/min). CONCLUSIONS:
      Aging does not affect the different functions of the liver in the same way. It
      increases hepatocellular uptake function, but decreases the metabolic function of
      hepatocytes and does not change excretion function. These discrepancies are
      likely to be of some importance in the study of drug metabolism and action, and
      so we suggest that results should be corrected for ICG extraction.

PMID- 15489058
TI  - Age effects on macrophage function vary by tissue site, nature of stimulant, and
      exercise behavior.
AB  - We explored the effects of aging on macrophage function in male BALB/c mice from
      three age groups: young (2 months), middle-aged (12 months), and old (21 months).
      Macrophages were collected from alveoli, peritonea, and spleens of each age
      group. Cells were cultured in vitro with LPS or LPS+IFN-gamma and assayed for
      production of IL-1, IL-12, NO, and TNF-alpha. Using herpes simplex virus-1, age
      related changes in intrinsic antiviral resistance (plaque assay) and extrinsic
      antiviral resistance (NO and TNF-alpha production) were determined in alveolar
      and/or peritoneal macrophages. Effects of chronic exercise on age-related
      macrophage changes were examined. In vitro, macrophages from the alveoli and
      spleen of older mice generally produced more cytokine and NO compared to younger
      counterparts. Conversely, macrophages from the peritonea of older mice generally
      produced less cytokine and NO in vitro compared to younger counterparts. Alveolar
      macrophages from both old and young mice showed higher intrinsic antiviral
      resistance to HSV-1 compared to middle-aged mice, while peritoneal macrophages
      from young mice showed reduced intrinsic resistance compared to those from both
      middle-aged and old mice. When challenged with HSV-1, a trend towards decreased
      peritoneal macrophage production of TNF-alpha and decreased alveolar macrophage
      production of IL-12 with advancing age was found. Chronic moderate exercise
      tended to reverse age-associated changes in macrophage function in old mice.

PMID- 15489059
TI  - Suppression of apoptosis by calorie restriction in aged kidney.
AB  - Programmed cell death by apoptosis is regarded as an organism's protective
      mechanism against the accumulation of defective cells. Apoptotic activity is
      shown to be elevated in most aged tissues, and its intracellular regulation is
      intricately manipulated by mitochondria. In this study, to determine the
      progression of apoptosis during aging, we investigated the expression of several
      key apoptosis-related markers in kidney of 12- and 24-month-old rats.
      Mitochondrial damage was detected by lipid peroxidation and Western blot analysis
      in several target apoptotic proteins in aged rat kidney. Our results showed that
      the expression levels of a pro-apoptotic Bax protein, was significantly enhanced
      at the age of 24 months, while an anti-apoptotic protein, Bcl-2, was reduced in
      the aged rat kidney. We also found that the cytosolic cytochrome c level was
      significantly increased in the aged kidney. However, these age-related changes
      were reversed by calorie restriction (CR), exhibiting its modulatory action on
      apoptotic activity. Furthermore, caspase-3 activation was markedly increased in
      kidney of 24-month-old rats fed ad libitum (AL), as indicated by the cleaved,
      active form of caspase-3 (17-19 kDa), which we found was replaced with the
      procaspase (32 kDa) in the CR rats of both age groups. We also found that a
      cleaved active form (85 kDa) of poly (ADP-ribose) polymerase (116 kDa inactivated
      form), which serves as a nuclear substrate for active caspase-3, was increased in
      aged AL kidney and was blunted by CR. In addition, to investigate the oxidative
      status in aged kidney, we measured and compared the malondialdehyde (MDA) and 4
      hydroxynonenal (HNE) levels in aged AL and CR rat kidneys. Our results showed
      increased MDA and HNE levels in aged AL rats, while these levels were markedly
      lower in CR rats, even at 24 months. These results indicate that the kidneys of
      rats fed ad libitum are under the influence of high oxidative stress compared to
      CR rats. Thus, our present data strongly suggest that the apoptotic activity
      observed in the aged kidney is likely modulated by the age-related oxidative
      status, and reversed by CR as a result of its anti-oxidative and anti-aging
      actions.

PMID- 15489060
TI  - Exploration of replicative senescence-associated genes in human dermal
      fibroblasts by cDNA microarray technology.
AB  - The aging process is known to be regulated by specific genes in various
      organisms, including yeast, the nematode C. elegans, fruitflies and mice. To
      explore the novel genes involved in aging process, we applied cDNA microarray
      technology to a replicative senescence model of human dermal fibroblasts (HDF).
      Eighty-four genes, including inflammatory genes, cell cycle regulatory genes,
      cytoskeletal genes, and metabolic genes were found to show more than two fold
      expressional differences in young and old fibroblasts. Furthermore, 31 genes were
      confirmed to be up- or down-regulated during replicative senescence by semi
      quantitative RT-PCR. The overexpressions of several genes including CD36,
      putative lymphocyte G0/G1 switch gene (G0S2), tumor protein D52-like 1 (TPD52L1),
      chemokine (C-X-C motif) ligand 6, myxovirus resistant gene 1 (MX1), and the down
      regulation of the immunoglobulin superfamily containing leucine-rich repeat
      (ISLR), neurotrimin, insulin-like growth factor 2 associated protein (IGF2A), and
      apoptosis-related RNA binding protein (NAPOR3) were newly identified. These
      results suggest that fibroblasts show the deregulation of various cellular
      processes, such as inflammatory response, mitosis, cell adhesion, transport,
      signal transduction, and metabolism during replicative senescence.

PMID- 15489061
TI  - Gene expression and regulation in H2O2-induced premature senescence of human
      foreskin fibroblasts expressing or not telomerase.
AB  - We compared the DNA-binding activity of transcription factors and gene expression
      patterns in BJ human diploid fibroblasts (HDFs) expressing or not telomerase
      (hTERT) in stress-induced premature senescence (SIPS). Senescent BJ cells were
      also studied. Hydrogen peroxide (H2O2)-induced SIPS modulated gene expression in
      both BJ and hTERT-BJ1 cells. Increased p21(WAF-1) mRNA level was amongst the
      common gene expression changes in BJ and hTERT-BJ1 cells induced by SIPS.
      Telomerase expression markedly changed gene expression in non-stressful
      conditions. Expression patterns of senescent BJ cells partially overlapped those
      of BJ and hTERT-BJ1 cells in SIPS. The basal levels of DNA-binding activity of NF
      kappaB and phosphorylated ATF-2 were different in BJ and hTERT-BJ1 cells. Both
      cell lines displayed a higher DNA-binding activity of p53 and HIF-1 72 h after
      H2O2 exposure. Our results indicate that similar mechanisms involving p21(WAF-1)
      and probably p53 are at work in BJ and hTERT-BJ1 HDFs under H2O2-induced SIPS,
      suggesting that generalized DNA damage rather than telomere length/telomerase
      plays a crucial role in H2O2induced SIPS. We propose that H2O2-induced SIPS
      involves a rearrangement of proliferative and apoptotic pathways. The marked
      changes in gene expression induced by telomerase suggest that apart from
      immortalization of HDFs, telomerase also alters the normal cellular functions but
      does not protect against SIPS.

PMID- 15489062
TI  - Oxidative stress and the mitochondrial theory of aging in human skeletal muscle.
AB  - According to the mitochondrial theory of aging, an age-related increase in
      oxidative stress is responsible for cellular damage and ultimately cell death.
      Despite compelling evidence that supports the mitochondrial theory of aging in
      some tissues, data regarding aging skeletal muscle are inconsistent. We collected
      resting muscle biopsies from the vastus lateralis, and 24 h urine samples from,
      young (N = 12, approximately 22 yr), and older (N = 12 approximately 72 yr) men.
      Urinary 8-OHdG was significantly higher in older as compared to younger men (Old:
      7714 +/- 1402, Young: 5333 +/- 1191 ng g(-1) creatinine: p = 0.005), as were
      levels of protein carbonyls (Old: 0.72 +/- 0.42, Young: 0.26 +/- 0.14 nmol mg(-1)
      protein: p = 0.007). MnSOD activity (Old: 7.1 +/- 0.8, Young: 5.2 +/- 1.8 U mg(
      1) protein: p = 0.04) and catalase activity (Old: 8.5 +/- 2.0, Young: 6.2 +/- 2.4
      micro mol min(-1) mg(-1) protein: p = 0.03) were significantly higher in old as
      compared to young men, respectively, with no differences observed for total or
      CuZnSOD. Full-length mtDNA appeared lower in old as compared to young men, and
      mtDNA deletions were present in 6/8 old and 0/6 young men (p = 0.003). The
      maximal activities of citrate synthase, and complex II+III, and IV were not
      different between young and old men, however, complex I+III activity was
      marginally higher in older as compared to younger men (Old: 2.5 +/- 0.5, Young:
      1.9 +/- 0.5 micromol min(-1) g(-1) w.w: p = 0.03) respectively. In conclusion,
      healthy aging is associated with oxidative damage to proteins and DNA, a
      compensatory up-regulation of antioxidant enzymes, and aberrations of mtDNA, with
      no reduction in electron transport chain maximal enzyme activity.

PMID- 15489063
TI  - The clinical and pathological characteristics of Chinese elderly patients with
      anti-neutrophil cytoplasmic autoantibodies associated small vessel vasculitis.
AB  - BACKGROUND: Anti-neutrophil cytoplasmic autoantibodies (ANCA) are serological
      markers of ANCA-associated small vessel vasculitis (AASV) which is one of common
      autoimmune diseases in Caucasian elderly population. OBJECTIVE: To analyze the
      clinical and pathological characteristics of Chinese elderly patients with AASV.
      METHODS: One-hundred forty one Chinese patients with AASV over 65 years old,
      diagnosed between 1997 and 2001 in the Institute of Nephrology of Peking
      University First Hospital, were retrospectively studied and their clinical and
      pathological data were analyzed. RESULTS: Patients diagnosed with AASV patient
      increased chronologically with the yearly ratio in 2000 and 2001 significantly (P
      < 0.05) higher than that in 1998 and before. Of the 141 patients, 72 were male
      and 69 were female with an average age of 68.2 years. 13 of the 141 were
      cytoplasmic ANCA (cANCA) positive and all recognized proteinase 3 (PR3). The
      other 128 were perinuclear ANCA (pANCA) positive and 120/128 recognized MPO,
      8/128 recognized both PR3 and MPO. Less than 50% of the patients were correctly
      diagnosed within 3 months. Clinically, 78% of the patients had fever and fatigue,
      52.5% had body weight loss, 96.4% had kidney involvement, of which 75% had
      elevated serum creatinine and 30.8% had acute renal failure. 76.6% had lung
      involvement, over half of them had hemoptysis or lung infiltrates. Other clinical
      manifestations included arthralgia (48.2%), muscle pain (39.7%), gastrointestinal
      symptoms (39.7%), eye involvement (28.3%) and ENT involvement (31.2%). In
      laboratory examinations, 94.4% of the patients had anemia, 62.4% had increased
      WBC count, 93.6% had increased ESR and 55.1% had increased CRP. CONCLUSIONS: More
      and more patients with AASV were diagnosed in Chinese elderly. Kidney was the
      most vulnerable organ to be involved and lung was the most important extra-renal
      organ to be affected. For elderly patients with multi-organ damage, an ANCA test
      should be performed in order to make an early diagnosis and start therapy in
      time.

PMID- 15489064
TI  - Impaired innate immunity predicts frailty in old age. The Leiden 85-plus study.
AB  - Aging is associated with an impaired capacity of the immune system to respond
      properly to danger signals, such as infection and cancer. Here, we provide
      evidence that an impaired innate immune response, as measured by a low production
      capacity of pro- and anti-inflammatory cytokines upon ex vivo standardized danger
      signalling with bacterial LPS, is predictive for frailty in elderly people:
      participants who at age 85-year produced low levels of LPS-induced IL-1beta, IL
      6, TNF-alpha and IL-1Ra and IL-10, were found to have a more than 2-fold elevated
      overall mortality risk, independent of chronic illnesses (relative risk is 2.21,
      95% confidence interval 1.27-3.82, P = 0.005), compared to peers with a higher
      production of any of the pro- and/or anti-inflammatory cytokines. A significant
      genetic association with the IL-10 promoter gene was found, indicating that
      people who are genetically predisposed low cytokine producers are at a higher
      risk of losing the capacity to respond properly to danger signals with aging. We
      conclude that a malfunctioning innate immune response predicts frailty in old age
      and is under specific (immuno-) genetic control.

PMID- 15489065
TI  - Peripheral blood markers of inflammation and functional impairment in elderly
      community-dwellers.
AB  - The cross-sectional association of functional impairment with several peripheral
      blood inflammatory markers (increased C-reactive protein (CRP), fibrinogen and
      leucocyte count, decreased cholesterol and albumin) was studied in 739 elderly
      community-dwellers. Functional measures included Tinetti test for gait and
      balance, and basic and Instrumental Activities of Daily Living. When considering
      each marker individually, only increased CRP was inversely associated with all
      functional measures independently of demographics, lifestyle, and comorbidity (P
      < 0.05). When considering the sum of positive markers, having more than one
      marker was also inversely associated with all functional measures (P < 0.05), but
      no clear gradient of impairment was found across increasing numbers of markers.
      When considering specific combinations of markers, having both increased CRP and
      at least another positive marker had a stronger association with functional
      impairment (P < 0.01 for all measures) than increased CRP alone (P > 0.05), or
      other positive markers alone or in combination (P < 0.05). In conclusion, in
      elderly individuals, peripheral blood markers of inflammation are associated with
      functional impairment independently of potential confounders. A specific
      combination of CRP with other markers provides a better correlate of functional
      impairment than both individual markers or a simple count of positive markers.

PMID- 15489066
TI  - Identification of a geographic area characterized by extreme longevity in the
      Sardinia island: the AKEA study.
AB  - High prevalence and low female/male ratio for validated centenarians are observed
      in Sardinia and these findings appear to be thus far unique to this island.
      Moreover a specific region on the island is characterized by exceptional male
      longevity. We calculated the extreme longevity index (ELI), defined as the
      percentage of persons born in Sardinia between 1880 and 1900, who became
      centenarians. A gaussian smoothing method was used in order to identify the so
      called 'Blue Zone', where longevity is concentrated in the central-eastern part
      of the island and covers all the mountainous areas of central Sardinia. The
      estimated life expectancy in the 'Blue Zone' is longer than in the remaining
      territory of the island especially for men and the male to female ratio among
      centenarians born in this area is 1.35 compared to 2.43 in the rest of Sardinia.
      The specific mechanism by which persons living in this territory were more likely
      to reach extreme longevity remains unknown but it is interesting to note that
      most of the 'longevity hot spots' identified in various regions of the world over
      the years have been located in mountainous geographical areas even if none of
      these longevity regions have been fully validated. An alternative and interesting
      hypothesis is that the high rate of inbreeding determined by frequent marriages
      between consanguineous individuals and low immigration rates have progressively
      decreased the variability of the genetic pool and facilitated the emergence of
      genetic characteristics that protect individuals from diseases that are major
      causes of mortality particularly in older individuals. Given the exceptionally
      high prevalence of male centenarians in the 'Blue Zone', it is reasonable to
      assume that either the environmental characteristics or the genetic factors, or
      both, exert their favorable effect more strongly in men than in women. Thus, the
      mechanism involved may be modulated by the hormonal milieu, or may be associated
      with genes located in the sex chromosomes.

PMID- 15489067
TI  - A comparison of left ventricular mass between two-dimensional echocardiography,
      using fundamental and tissue harmonic imaging, and cardiac MRI in patients with
      hypertension.
AB  - PURPOSE: To compare left ventricular mass (LVM) as measured by two-dimensional
      (2D) echocardiography using two different calculation methods: truncated ellipse
      (TE) and area length (AL), in both fundamental and tissue harmonic imaging
      frequencies, to LVM as measured by, the current gold standard, cardiac magnetic
      resonance imaging (MRI). Turbo gradient echo (TGE) pulse sequence was utilized
      for MRI. MATERIALS AND METHODS: Thirty-two subjects with history of hypertension
      were recruited. The images were acquired, contours were traced and the LVM was
      calculated for all four different echocardiography methods as well as for the
      cardiac MRI method. The intra-observer variabilities were calculated. The four
      different echocardiography methods were compared to cardiac MRI using the method
      described by Bland and Altman. RESULTS: Twenty-five subjects had adequate paired
      data sets. The mean LVM as measured by cardiac MRI was 162+/-55 g and for the
      four different echocardiography methods were: fundamental AL 165+/-55 g, harmonic
      AL 168+/-53 g, fundamental TE 148+/-50 g, harmonic TE 149+/-45 g. The intra
      observer variability for cardiac MRI method, expressed as bias +/- 1 standard
      deviation of the difference (S.D.D.), was 2.3+/-9.2 g and for the four different
      echocardiography methods were: fundamental TE 0.4+/-26.8 g, fundamental AL 0.6+/
      27.0 g, harmonic TE 6.7+/-21.8 g, harmonic AL 6.4+/-22.9 g. The mean LVM for the
      AL method was closest to the cardiac MRI technique, while TE underestimated LVM.
      The 95% limits of agreement were consistently wide for all the 2D
      echocardiography modalities when compared with the cardiac MRI technique.
      CONCLUSION: The intra-observer variability in measurements of 2D
      echocardiographic LVM, together with the wide limits of agreement when compared
      to the gold standard (cardiac MRI) are sufficiently large to make serial
      estimates of LVM, of single patients or small groups of subjects, by 2D
      echocardiography, unreliable.

PMID- 15489068
TI  - On the value of geometry-based models for left ventricular volumetry in magnetic
      resonance imaging and electron beam tomography: a Bland-Altman analysis.
AB  - OBJECTIVE: Methodological comparison of ellipsoid model-based approaches and
      Simpson method to evaluate left ventricular volumetric parameters by magnetic
      resonance (MR) and electron beam tomography (EBT) and analysis of the origin of
      possible discrepancies. METHODS AND MATERIAL: 100 subjects (87 patients, 13
      healthy volunteers) were studied in MR in various cardiac views and EBT long axis
      view to determine left ventricular volumes and masses by applying (rotational)
      ellipsoid and Simpson model. Observer variation and method agreement was
      quantified by means of variance component and Bland-Altman analysis. RESULTS:
      Simpson approach showed smaller observer variability than all ellipsoid
      approaches. All geometry-based models gave smaller left ventricular volumes than
      Simpson approach, the bias in mass determination was minimal. Whereas high
      correlation coefficients (typically 0.85-0.95) for left ventricular volume and
      mass measurements indicated satisfying correspondence between methods, large 95%
      limits of agreement made a transfer of results for single subjects between
      Simpson and ellipsoid approaches difficult and between different geometry-based
      models almost impossible. Because 95% limits of agreement and observer
      variability of geometry-based approaches were of equal order, the latter could be
      identified as main limiting factor of methodological agreement. CONCLUSION: MR
      Simpson approach is superior to all ellipsoid model-based approaches, because
      observer variability is smaller.

PMID- 15489069
TI  - CT techniques for imaging the lung: recommendations for multislice and single
      slice computed tomography.
AB  - The introduction of multislice computed tomography (MSCT) has provided the
      thoracic radiologist with a powerful tool with which to image the lungs.
      Enthusiasm for new protocols should be tempered with concerns over the potential
      increase in radiation dose, and before older protocols are abandoned there should
      be good evidence that newer protocols are objectively superior. Ultimately, the
      best protocol is one that provides the most relevant clinical information at the
      lowest dose possible.

PMID- 15489070
TI  - High-resolution CT imaging of the lung for patients with primary Sjogren's
      syndrome.
AB  - PURPOSE: To assess pulmonary abnormalities in patients with primary Sjogren's
      syndrome (PSS) using high-resolution computed tomography (HRCT). MATERIAL AND
      METHODS: The HRCT scans of 24 patients with the diagnosis PSS were
      retrospectively reviewed regarding the presence, extension and distribution of 16
      pathological findings. RESULTS: Nineteen patients (79.2%) showed pathological
      findings and in five patients (21.8%) the HRCT scan was judged to be normal. A
      predominance of abnormalities in the lower lobes and subpleural areas was
      detected. The following pathologies were found: bronchiectasis, thin-walled cysts
      and small pulmonary nodules (46.2%), ground-glass attenuation and emphysema
      (37.8%), interlobular-septal thickening (29.4%), honeycombing (25.2%), bronchial
      wall thickening, tree-in-bud pattern (21.0%), mosaic perfusion (16.8%),
      architectural distortion (12.6%). Airspace consolidation, air trapping, large
      nodules (10-30mm) and masses (>30mm), mediastinal lymph node enlargement (>15mm)
      and free pleural fluid were seen each in 4.2%. In 7 of the 11 patients with thin
      walled cysts areas of ground-glass attenuation were detected. CONCLUSION: HRCT
      seems is contributive to the characterization of the wide variety of lung
      abnormalities in PSS. Airway disease alone or in association with the presence of
      varying degrees of interstitial disease represents the main findings in
      accordance with earlier reports. Unexpectedly, almost half of the patients had
      thin-walled cysts on the HRCT scans, which etiology is unclear but could be
      associated with areas of ground-glass attenuation indicating LIP.

PMID- 15489071
TI  - Dynamic MR imaging: value of differentiating subtypes of peripheral small
      adenocarcinoma of the lung.
AB  - PURPOSE: To determine the utility of dynamic magnetic resonance imaging (MRI) in
      the differential subtyping of small adenocarcinomas of the lung. MATERIALS AND
      METHODS: Twenty-nine pathologically diagnosed peripheral adenocarcinomas (less
      than 20 mm in diameter) underwent dynamic contrast-enhanced MRI. Maximum relative
      enhancement ratio, slope of enhancement, and corrected start time of enhancement
      were calculated from signal intensity-time curve of pulmonary lesion for each
      subject, and were statistically compared among bronchioloalveolar carcinoma (BAC)
      group (7 cases), mixed BAC group (10 cases), and adenocarcinoma group (12 cases).
      RESULTS: Maximum relative enhancement ratio (P<0.001) and slope of enhancement
      (P<0.001) of BAC group were significantly higher than those of mixed BAC and
      adenocarcinoma groups. Start times of BAC group were significantly earlier than
      those of mixed BAC (P=0.0001) and adenocarcinoma groups (P<0.0001). Adapting the
      thresholds values of MR indexes from the positive tests, sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy
      for differentiating BAC from other subtypes were 85.7, 100.0, 100.0, 95.7, and
      96.6%, respectively. CONCLUSIONS: Dynamic MRI is useful for differentiating
      subtypes of small peripheral adenocarcinoma.

PMID- 15489072
TI  - Bronchial reactivity in hyperresponsive patients and healthy individuals:
      demonstration with high resolution computed tomography.
AB  - OBJECTIVE: High resolution computed tomography (HRCT) was used to assess the
      extent of bronchial reactivity after inhalative bronchoprovocation and dilation
      in hyperresponsive patients and healthy subjects. PATIENTS AND METHODS: Patients
      with mild intermittent asthma, 15 with a >20% decrease in FEV1 and a >10 mmHg
      (PC20+) in PaO2, 12 with a <20% decrease in FEV1 and a >10 mmHg (PC20-) in PaO2
      after provocation, and eight healthy humans were included in the study. Changes
      in cross-sectional area in a total of 1256 bronchi and in bronchial wall area
      (792 bronchi) were evaluated after histamine-triggered bronchoprovocation and
      salbutamol-induced bronchodilation at high lung volumes (FVC 80%). Data were
      compared with the results of pulmonary function tests (FEV1, PaO2, PaCO2).
      RESULTS: In all groups, a significant decrease in bronchial cross-sectional area
      (P<0.001) and a significant increase in bronchial wall area (P<0.001) were
      observed subsequent to bronchoprovocation. After bronchodilation, the increase in
      cross-sectional area (P<0.001) and the further increase in airway wall area
      (P<0.01) were significant in all groups. In PC20+ and PC20- asthmatics,
      significant differences (P<0.05) in PaO2, >10 mmHg between baseline and
      provocation were observed. In healthy persons, the PaO2 decrease was <10 mmHg
      (P>0.05). After histamine provocation, the decrease in FEV1 was measured in the
      PC20+ group, whereas a <20% FEV1 decrease was found in the PC20- and the control
      groups, respectively. No significant correlations were observed between
      radiological data and the results of pulmonary function tests. CONCLUSIONS: HRCT
      demonstrated bronchial reactivity in hyperresponsive patients and, unexpectedly,
      in healthy subjects. The applied pulmonary function tests failed to characterize
      bronchial reactions in the healthy subjects. Based on these results, HRCT is a
      useful tool by which to achieve a comprehensive understanding of the
      pathophysiological processes in asthmatic patients.

PMID- 15489073
TI  - Presence and HRCT quantification of bronchiectasis in coal workers.
AB  - PURPOSE: The purpose of this study was to evaluate the presence of bronchiectasis
      in coal workers with or without coal worker pneumoconiosis (CWP) and to assess
      the extent of bronchiectasis, severity of bronchial wall dilatation and
      thickening by high resolution computed tomography (HRCT). MATERIALS AND METHODS:
      The retrospective study consisted of HRCT archieves of 93 coal workers. The coal
      workers with previous diagnosis of COPD (six), asthma (one) and tuberculosis
      (three) were excluded. Five coal workers with progressive massive fibrosis were
      not included into the study. The resulting patient group consisted of 78 patients
      (43 CWP; 35 non-CWP). Pneumoconiosis profusions of CWP workers were between p0/1
      and p2/2 according to ILO 1980 chest X-ray classification. HRCT examinations of
      all subjects were evaluated for the presence, extent, dilatation and thickness of
      bronchiectasis. Analysis of extent, dilatation and thickness were performed
      according to established criteria. RESULTS: The diagnosis of bronchiectasis was
      put on 19 of 43 CWP (44.1%) and 7 of 35 non-CWP workers (20.0%). There were
      statistically significant differences between bronchiectasis positive and
      negative coal workers with CWP concerning age and exposure duration (P = 0.012
      and 0.009, respectively). Then, multiple logistic regression analysis was
      performed to define exact risk factors. Exposure duration was only found to be
      related with presence of bronchiectasis [(odds ratio) OR = 1.494, 95% confidence
      interval 1.168-1.912]. CONCLUSIONS: The data from the present study shows that
      bronchiectasis is frequent and severe in CWP workers than without. Bronchiectasis
      is influenced by coal dust exposure. Thus, coal dust protection measures must be
      controlled efficiently to prevent bronchiectasis in coal workers.

PMID- 15489074
TI  - Bronchiolitis obliterans following exposure to sulfur mustard: chest high
      resolution computed tomography.
AB  - BACKGROUND: Pulmonary complications are known to occur in over half of the
      patients exposed to sulfur mustard (SM). Chemical weapons of mass destruction
      (WMD) including SM were used by Iraq during Iran-Iraq war between 1983 and 1989.
      We undertook this study to evaluate the chest high resolution computerized
      tomography (HRCT) as a diagnostic tool in patients with documented exposure to SM
      and chronic respiratory symptoms. METHOD: The medical records of 155 patients
      exposed to SM during Iran-Iraq war and suffered respiratory complications were
      reviewed. Chest HRCTs of these patients were examined. Ten healthy controls with
      no history of exposure to HD were matched for age, gender, and chest HRCT
      protocol applied. RESULTS: Fifty chest HRCTs of these patients were randomly
      selected for this study. The most frequent findings were; air trapping 38 (76%),
      bronchiectasis 37 (74%), mosaic parenchymal attenuation (MPA) 36 (72%), irregular
      and dilated major airways 33 (66%) bronchial wall thickening (BWT) 45 (90%), and
      interlobular septal wall thickening (SWT) 13 (26%), respectively. Air trapping in
      one patient (10%) was the only positive finding in the control group.
      CONCLUSIONS: Chest HRCT findings of bronchiectasis, air trapping, MPA, SWT, and
      BWT were seen in our patients 15 years after exposure to HD. These findings
      suggest the diagnosis of bronchiolitis obliterans (BO). We did not encounter
      chest HRCT features consistent with pulmonary fibrosis.

PMID- 15489075
TI  - Cavitary pulmonary tuberculosis HIV-related.
AB  - INTRODUCTION: It was usually assumed that pulmonary tuberculosis (TB) in HIV
      seropositive patients represents reactivation TB, despite the radiographic
      appearance frequently consistent rather with a recent disease. Hence, these
      radiographic features were considered "atypical". We have hypothesised that the
      so called "atypical" radiographic features could be due to a greater proportion
      of primary TB among these patients, representing the typical appearance of
      primary radiological pattern. MATERIAL AND METHODS: We reviewed chest imaging of
      219 HIV+ patients with microbiological proven pulmonary tuberculosis, who were
      assessed for the presence, number, distribution of cavitations and for associated
      pulmonary parenchymal abnormalities, adenopathies and pleural effusion, and were
      classified as a primary or post-primary pattern. RESULTS: The patients with post
      primary pattern were 50%, and the rate of cavitation was 63%, not wandering off
      the general population. Cavities still occurred with similar proportion in groups
      with CD4 <200 or >200cells/mm(3). CONCLUSION: We suggest that HIV-related
      pulmonary tuberculosis is typical in its radiological appearances, consistent
      with those of the general population, and this could be confirmed by the most
      recent molecular epidemiological techniques that allow to definitely classify the
      tuberculosis episodes as either primary or post-primary disease.

PMID- 15489076
TI  - Pulmonary tuberculosis in patients with idiopathic pulmonary fibrosis.
AB  - OBJECTIVES: Patients with idiopathic pulmonary fibrosis (IPF) have an increased
      risk of pulmonary tuberculosis. However, detecting pulmonary tuberculosis may be
      difficult due to the underlying fibrosis. The aim of this report is to describe
      the radiological and clinical findings of pulmonary tuberculosis in patients with
      idiopathic pulmonary fibrosis. MATERIALS AND METHODS: We reviewed 143 consecutive
      patients in whom IPF was diagnosed by either the histological or radio-clinical
      criteria. Among them, nine patients were histologically (n=2) or
      bacteriologically (n=7) confirmed to have active pulmonary tuberculosis. The
      location and patterns of pulmonary tuberculosis were examined on a thin section
      CT scan. RESULTS: The most common thin section CT findings were subpleural
      nodules (n=6; mean diameter, 3.2 cm) and a lobar or segmental consolidation
      (n=3). The lesions were located most commonly in the right lower lobe (n=4). The
      incidence of tuberculosis in patients with idiopathic pulmonary fibrosis was more
      than five times higher than that of the general population. CONCLUSION: The
      atypical manifestation of pulmonary tuberculosis is common in patients with
      idiopathic pulmonary fibrosis, which may mimic lung cancer or bacterial
      pneumonia.

PMID- 15489077
TI  - Volumetric expiratory high-resolution CT of the lung.
AB  - We developed a volumetric expiratory high-resolution CT (HRCT) protocol that
      provides combined inspiratory and expiratory volumetric imaging of the lung
      without increasing radiation exposure, and conducted a preliminary feasibility
      assessment of this protocol to evaluate diffuse lung disease with small airway
      abnormalities. The volumetric expiratory high-resolution CT increased the
      detectability of the conducting airway to the areas of air trapping (P<0.0001),
      and added significant information about extent and distribution of air trapping
      (P<0.0001).

PMID- 15489078
TI  - Bronchopulmonary sequestration: radiologic findings.
AB  - Bronchopulmonary sequestration (BPS) is a nonfunctioning bronchopulmonary tissue
      that is separate from the tracheobronchial tree and receives arterial blood from
      the systemic circulation. BPS has a wide spectrum of imaging findings. Surgery is
      generally indicated for the treatment of BPS. It is important to demonstrate the
      arterial supply and venous drainage of the sequestered segment preoperatively.
      Today, with the help of noninvasive imaging techniques such as computed
      tomography (CT) and magnetic resonance imaging (MRI), preoperative diagnosis of
      BPS can be made easily, so, invasive techniques such as angiography are not
      required frequently. In this report, radiological findings of BPS were
      retrospectively reviewed.

PMID- 15489079
TI  - Biomass exposure and the high resolution computed tomographic and spirometric
      findings.
AB  - BACKGROUND: The adverse health effects of biomass fuel exposure (BFE) is complex
      and widespread. According to our knowledge, the interstitial lung disease due to
      BFE is not clear in literature. OBJECTIVE: In this descriptive crossectional
      study, the main objective was to assess the effects of BFE on the respiratory
      system. METHODS: Patient group was included non-smoker 21 woman and the control
      group was included non-smoker 22 woman. High resolution computed tomographic
      (HRCT) examinations were made with supin and prone positions in two groups. The
      spirometric measurements, including the diffusion capacity at rest for carbon
      monoxide, single breath (DLCO), were also made. RESULTS: It was found that BFE
      caused obstructive and restrictive spirometric impairments. The prevalence of the
      fibrotic bands, peribronchovascular thickenings, nodular radio opacities, and
      curvilinear densities in the high resolution computed tomographic examinations
      were 7, 5, 7, and 16 times higher in the exposure group than the control group,
      respectively. There was a significant positive correlation between the forced
      vital capacity (FVC), forced expiratory volume first second (FEV(1)), FEV(1)/FVC,
      forced expiratory flow during middle half of forced vital capacity (FEF25-75),
      DLCO and the volumetric densities of the HRCT slices with deep expiration in
      prone position. CONCLUSIONS: We think that, the findings due to BFE, pose a
      special situation and it can be named "biomass lung".

PMID- 15489080
TI  - Centrically reordered inversion recovery half-Fourier single-shot turbo spin-echo
      sequence: improvement of the image quality of oxygen-enhanced MRI.
AB  - PURPOSE: The purpose of the study presented here was to determine the improvement
      in image quality of oxygen-enhanced magnetic resonance (MR) subtraction imaging
      obtained with a centrically reordered inversion recovery half-Fourier single-shot
      turbo spin-echo (c-IR-HASTE) sequence compared with that obtained with a
      conventional sequentially reordered inversion recovery single-shot HASTE (s-IR
      HASTE) sequence for pulmonary imaging. MATERIALS AND METHODS: Oxygen-enhanced MR
      imaging using a 1.5 T whole body scanner was performed on 12 healthy, non-smoking
      volunteers. Oxygen-enhanced MR images were obtained with the coronal two
      dimensional (2D) c-IR-HASTE sequence and 2D s-IR-HASTE sequence combined with
      respiratory triggering. For a 256x256 matrix, 132 phase-encoding steps were
      acquired including four steps for phase correction. Inter-echo spacing for each
      sequence was 4.0 ms. The effective echo time (TE) for c-IR-HASTE was 4.0 ms, and
      16 ms for s-IR-HASTE. The inversion time (TI) was 900 ms. To determine the
      improvement in oxygen-enhanced MR subtraction imaging by c-IR-HASTE, CNRs of
      subtraction image, overall image quality, and image degradation of the c-IR-HASTE
      and s-IR-HASTE techniques were statistically compared. RESULTS: CNR, overall
      image quality, and image degradation of c-IR-HASTE images showed significant
      improvement compared to those s-IR-HASTE images (P<0.05). CONCLUSION: Centrically
      reordered inversion recovery half-Fourier single-shot turbo spin-echo (c-IR
      HASTE) sequence enhanced the signal from the lung and improved the image quality
      of oxygen-enhanced MR subtraction imaging.

PMID- 15489081
TI  - Oblique approach of computed tomography guided needle biopsy using multiplanar
      reconstruction image by multidetector-row CT in lung cancer.
AB  - The purpose of this study was to establish the technique of multiplanar
      reconstruction (MPR) with multidetector-row (MDR) computed tomography (CT) guided
      needle biopsy for the diagnosis to access very difficult lesions. The CT guided
      percutaneous biopsy are well-established methods to obtain cytological and
      histological material such as the peripheral tumors in lung cancer. Occasionally,
      the conventional CT cannot permit planning a trajectory to avoid passage through
      bones, avoidance of bullae, fissures or vessels. In addition, some lesions are
      situated in less favorable locations such as those in the costophrenic recess or
      close to the mediastinum. Rarely can we diagnose them. MPR with MDR-CT has
      recently become widely available with applications for thoracic lesions. MPR
      images have been used to evaluate the location of small peripheral lung nodules
      to the relation of bullaes, vessels, and costophrenic recess. To diagnose these
      lesions, the usefulness of MPR were evaluated for an planning of an oblique
      approach of CT guided needle biopsy. MPR images were reconstructed as a line from
      the needle entry point to the target lesion. The first oblique image applied as
      the direction of posterior-anterior and cranio-caudal axis, and the second
      oblique image applied as the direction of posterior-anterior and left-right.
      Eleven out of 151 patients were required MPR technique to allow possible access
      to target, because of avoidance of bone and fissures in the needle pass or
      located in the costophrenic recess, between April 2001 and December 2002. The
      5/11 patients were at the upper site (segment 1, 2 and 6) behind the scapula and
      ribs, 3/11 patients were at the lower lobe (segment 10) in the costophrenic
      recess, and 3/11 were middle lobe or segment 3 covered by the ribs and fissures.
      All the lesions except one were histologically diagnosed. Five patients were
      adenocarcinoma, and the other five patients were benign tumors. Pneumothorax
      occurred in one patient before we obtained the specimens. MPR guided needle
      biopsy with oblique approach was thought to be useful for diagnosis of very
      difficult thoracic lesions and would obviate an unnecessary surgical
      thoracoscopy.

PMID- 15489082
TI  - The quantification of infarct size.
AB  - We sought to summarize the published evidence regarding the measurement of
      infarct size by serum markers, technetium-99m sestamibi single-photon emission
      computed tomography (SPECT) myocardial perfusion imaging, and magnetic resonance
      imaging. The measurement of infarct size is an attractive surrogate end point for
      the early assessment of new therapies for acute myocardial infarction. For each
      of these three approaches, we reviewed reports published in English providing the
      clinical validation for the measurement of infarct size and the relevant clinical
      trial experience. The measurement of infarct size by serum markers has multiple
      theoretical and practical limitations. The measurement of troponin is promising,
      but the available data validating this marker are limited. Sestamibi SPECT
      imaging has five separate lines of published evidence supporting its validity and
      has received extensive study in multicenter trials. Magnetic resonance imaging
      has great promise but has less clinical validation and no multicenter trial
      experience. Therefore, SPECT sestamibi imaging is currently the best available
      technique for the quantitation of infarct size to assess the incremental
      treatment benefit of new therapies in multicenter trials of acute myocardial
      infarction.

PMID- 15489083
TI  - Diastolic dysfunction: can it be diagnosed by Doppler echocardiography?
AB  - Heart failure with a normal ejection fraction (HFNEF) predominantly afflicts
      older, female individuals and is considered to be a consequence of diastolic
      dysfunction. Doppler echocardiography has become the standard method for
      identifying and characterizing diastolic function. However, the important
      distinction between Doppler measures of filling dynamics and true indexes of
      intrinsic ventricular diastolic chamber properties is not widely appreciated.
      Herein, we delineate physiologic measures of intrinsic ventricular diastolic
      function, as determined by pressure volume analysis, and compare and contrast
      these measures with those derived from Doppler echocardiography. Doppler-derived
      indexes of ventricular filling do not provide specific information on intrinsic
      passive diastolic properties, and thus, abnormal filling dynamics do not
      necessarily equate with intrinsic myocardial diastolic dysfunction. This raises a
      fundamental question as to whether delayed relaxation and/or stiffened passive
      properties are the unifying pathophysiologic mechanisms in all patients who
      present with HFNEF.

PMID- 15489084
TI  - Highlights of Heart Rhythm 2004, the Annual Scientific Sessions of the Heart
      Rhythm Society: May 19 to 22, 2004, in San Francisco, California.
AB  - Heart Rhythm 2004, the 25th Annual Scientific Sessions of the Heart Rhythm
      Society (formerly the North American Society of Pacing and Electrophysiology),
      met in San Francisco in May 2004. The meeting is the world's premier forum for
      the presentation of research and the exchange of state-of-the-art information in
      cardiac electrophysiology and pacing. Major new research findings were presented
      on the value of implantable cardioverter-defibrillator therapy, noninvasive
      methods for risk stratification, treatment of vasovagal syncope, radiofrequency
      ablation for atrial fibrillation, resynchronization therapy for heart failure,
      and new insights from basic science into the mechanisms of cardiac arrhythmias.

PMID- 15489085
TI  - Comparative effects of antiplatelet, anticoagulant, or combined therapy in
      patients with valvular and nonvalvular atrial fibrillation: a randomized
      multicenter study.
AB  - OBJECTIVES: This trial evaluated the efficacy and safety of the combination of
      antiplatelet and moderate-intensity anticoagulation therapy in patients with
      atrial fibrillation associated with recognized risk factors or mitral stenosis.
      BACKGROUND: Warfarin was more effective than aspirin in preventing stroke in
      these patients; combined therapy with low anticoagulant intensity was
      ineffective. Mitral stenosis patients were not investigated. METHODS: We
      performed a multicenter randomized trial in 1,209 patients at risk. The
      intermediate-risk group included patients with risk factors or age >60 years: 242
      received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and
      235 received a combination of both. The high-risk group included patients with
      prior embolism or mitral stenosis: 259 received anticoagulants and 236 received
      the combined therapy. Median follow-up was 2.76 years. Primary outcome was a
      composite of vascular death and nonfatal stroke or systemic embolism. RESULTS:
      Primary outcome was lower in the combined therapy than in the anticoagulant arm
      in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval
      (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to
      0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined
      therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients
      had similar embolic event rates during anticoagulant therapy. CONCLUSIONS: The
      combined antiplatelet plus moderate-intensity anticoagulation therapy
      significantly decreased the vascular events compared with anticoagulation alone
      and proved to be safe in atrial fibrillation patients.

PMID- 15489086
TI  - Reconsidering combined antiplatelet and anticoagulant therapy in atrial
      fibrillation.

PMID- 15489087
TI  - Monocyte-derived tissue factor contributes to stent thrombosis in an in vitro
      system.
AB  - OBJECTIVES: This study evaluated the role of circulating tissue factor (TF) in
      mediating thrombus formation on stents in an in vitro model of stent perfusion.
      BACKGROUND: The traditional view of coagulation has recently been challenged by
      the demonstration that TF is present in circulating blood. The potential
      contribution of this intravascular pool of TF to thrombus formation on stents is
      not known. METHODS: Coronary stents were placed in parallel silicone tubes
      connected to a roller pump that was set to pump blood at a flow rate of 10
      ml/min. Stents were then exposed to heparinized blood from healthy volunteers for
      120 min. RESULTS: The presence of the stent in the circuit caused a significant
      increase in monocyte TF expression, but only monocytes with attached platelets
      stained positive for TF. Thrombi formed on stents and the thrombi stained
      positive for TF. Pretreatment of blood with a monoclonal antibody against TF
      (cH36) caused a 56% reduction in (125)I-fibrin(ogen) deposition on stents
      compared with controls (p = 0.002). Monocyte depletion of blood reduced (125)I
      fibrin(ogen) deposition by 45% (p = 0.01) and TF staining in the thrombus by 83%
      (p = 0.01). Pretreatment of blood with a monoclonal antibody against P-selectin
      reduced (125)I-fibrin(ogen) deposition by 24% (p = 0.04). Perfusion of stents
      with leukocyte-reduced platelet-rich plasma (PRP) produced small thrombi and
      treatment of PRP with cH36 reduced (125)I-fibrin(ogen) deposition by 43% (p =
      0.01). CONCLUSIONS: Circulating TF plays a pivotal role in thrombus formation on
      stents. Monocytes appear to be the main, but not only, source of TF depositing in
      the thrombus.

PMID- 15489088
TI  - Proteomic analysis of plasma from patients during an acute coronary syndrome.
AB  - OBJECTIVES: The aim of this study was to analyze modifications in the plasma
      protein map during an acute coronary syndrome (ACS) using proteomics. BACKGROUND:
      Proteomics is a new technology that allows the detection and identification of
      several proteins at a given time in a sample. METHODS: Plasma from 19 patients,
      11 with acute myocardial infarction (AMI) and 8 with unstable angina (UA), was
      investigated. The control group included nine age-matched volunteers. RESULTS: In
      two-dimensional electrophoresis using a pH range of 4 to 7, constant differences
      were found in at least four different areas within the plasma protein map. In
      area 1, we identified the presence of seven alpha(1)-antitrypsin (AAT) isoforms
      in plasma from control subjects. alpha(1)-antitrypsin isoform 1 was undetectable
      in plasma from UA and AMI patients. The AAT isoforms 5, 6, and 7 were reduced in
      plasma from AMI patients when compared with UA patients. Three fibrinogen gamma
      chain isoforms were identified in area 2. Fibrinogen gamma chain isoforms 1 and 2
      were increased in AMI patients with respect to UA patients. Five apolipoprotein A
      I isoforms were identified in area 3. All of them were reduced in plasma from AMI
      patients with respect to UA patients. In area 4, the gamma-immunoglobulin heavy
      chains were detected and were found increased in plasma from ACS patients.
      CONCLUSIONS: Plasma proteomic analysis makes it possible to develop a map of the
      protein isoforms that are expressed in plasma during an ACS.

PMID- 15489089
TI  - Heart disease leaves its mark: proteomics-based biosignatures in acute coronary
      syndromes.

PMID- 15489090
TI  - The association among renal insufficiency, pharmacotherapy, and outcomes in 6,427
      patients with heart failure and coronary artery disease.
AB  - OBJECTIVES: This study was designed to examine the use of cardiovascular
      medications and outcomes in patients with heart failure (HF) and renal
      dysfunction. BACKGROUND: Renal insufficiency is associated with poorer outcomes
      in patients with HF, but the mechanisms are uncertain. In particular, the degree
      of therapeutic nihilism in these patients, and whether it is appropriate, is
      unclear. METHODS: This was a prospective cohort study with a one-year follow-up.
      RESULTS: In 6,427 patients with cardiologist-diagnosed HF and angiographically
      proven coronary artery disease (mean age 69 years; 65% men; one-year mortality,
      10%), 39% had creatinine clearances <60 ml/min. Patients with renal insufficiency
      were less likely to be prescribed angiotensin-converting enzyme (ACE) inhibitors,
      beta-blockers, statins, or aspirin (all p < 0.001). However, users of aspirin
      (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.57 to 0.85), statins (OR
      0.79, 95% CI 0.64 to 0.97), and beta-blockers (OR 0.75, 95% CI 0.62 to 0.90) were
      less likely to die in the subsequent 12 months than nonusers, irrespective of
      renal function (all OR adjusted for covariates including atherosclerotic burden
      and ejection fraction). Although ACE inhibitor users with creatinine clearances >
      or =60 ml/min had lower 12-month mortality (OR 0.72, 95% CI 0.48 to 0.99), ACE
      inhibitor users with clearances <60 ml/min did not (OR 1.21, 95% CI 0.97 to
      1.51). CONCLUSIONS: Renal insufficiency is common in patients with HF and
      coronary artery disease, and these patients have more advanced coronary
      atherosclerosis. Patients with renal insufficiency are less likely to be
      prescribed efficacious therapies, but have better outcomes if they receive these
      medications.

PMID- 15489091
TI  - Renal insufficiency as an independent predictor of mortality among women with
      heart failure.
AB  - OBJECTIVES: We sought to explore the association between renal insufficiency and
      mortality among women with heart failure (HF) and to evaluate this risk by the
      presence of preserved or depressed systolic function. BACKGROUND: Although HF is
      common in older women, little is known about their risk factors for mortality.
      METHODS: This prospective cohort study retrospectively analyzed data from the
      Heart and Estrogen/progestin Replacement Study (HERS). Of the 2,763 women in
      HERS, 702 had HF. Renal function was categorized as creatinine clearance (CrCl)
      >60 ml/min, 40 to 60 ml/min, and <40 ml/min. We used proportional hazards models
      to evaluate the association between renal insufficiency and mortality. RESULTS:
      Over a mean 5.8 years, 228 women with HF died (32%). Renal insufficiency was
      strongly associated with mortality, even after adjustment for co-morbid
      conditions, systolic function, and medications (adjusted hazard ratio [HR] 1.53,
      95% confidence interval [CI] 1.09 to 2.16 for CrCl 40 to 60 ml/min; adjusted HR
      2.40, 95% CI 1.60 to 3.62 for CrCl <40 ml/min). Preserved or depressed systolic
      function did not modify the association between renal insufficiency and mortality
      risk, but the use of angiotensin-converting enzyme (ACE) inhibitors did modify
      this risk (ACE users: adjusted HR = 0.9, 95% CI 0.6 to 1.6; ACE nonusers:
      adjusted HR 2.1, 95% CI 1.3 to 3.2; p = 0.02 for interaction). Compared with
      other risk factors for mortality, renal insufficiency had the highest population
      attributable risk (27%). CONCLUSIONS: Renal insufficiency was a major predictor
      of mortality among women with HF and preserved or depressed systolic function.
      This risk was attenuated by the use of ACE inhibitors.

PMID- 15489092
TI  - The diagnosis of heart failure in the community. Comparative validation of four
      sets of criteria in unselected older adults: the ICARe Dicomano Study.
AB  - OBJECTIVES: We sought to compare construct and predictive validity of four sets
      of heart failure (HF) diagnostic criteria in an epidemiologic setting.
      BACKGROUND: The prevalence estimates of HF vary broadly depending on the
      diagnostic criteria. METHODS: Data were collected in a survey of community
      dwellers who were > or =65 years of age living in Dicomano, Italy. At baseline,
      HF was diagnosed with the criteria of the Framingham, Boston, and Gothenburg
      studies and of the European Society of Cardiology (ESC). Left ventricular mass
      index and ejection fraction, left atrium systolic dimension, lower extremity
      mobility disability, summary physical performance score, and 6-min walk test were
      compared between HF and non-HF participants to test for construct validity of
      each set of criteria. Predictive validity was evaluated with follow-up assessment
      of cardiovascular mortality, incident disability, and HF-related
      hospitalizations. Comparisons were adjusted for demographics, comorbidity, and
      psychoaffective status. RESULTS: Of 553 participants, 11.9%, 10.7%, 20.8%, and
      9.0% had HF, according to Framingham, Boston, Gothenburg, and ESC criteria,
      respectively. In terms of construct validity, Framingham and Boston criteria
      discriminated HF from non-HF participants better than Gothenburg and ESC criteria
      across the measures of cardiac function and global performance. The Boston
      criteria showed a superior predictive validity because they indicated a
      significantly greater adjusted risk of cardiovascular death (hazard ratio3.9, 95%
      confidence interval 1.2 to 13.2), incident disability, and hospitalizations in
      participants with HF. CONCLUSIONS: The Boston criteria are preferable to
      Framingham, Gothenburg, and ESC criteria for the diagnosis of HF in older
      community dwellers because they have good construct validity and more accurately
      predict cardiovascular death, incident disability, and hospitalizations.

PMID- 15489093
TI  - Matrix metalloproteinases and their tissue inhibitors in pressure-overloaded
      human myocardium during heart failure progression.
AB  - OBJECTIVES: We studied the role of matrix metalloproteinases (MMPs) and their
      tissue inhibitors (TIMPs) in fibrosis formation in the transition from
      hypertrophy to heart failure (HF) as well as the cellular source of MMPs and
      TIMPs. BACKGROUND: Human pressure-overloaded hearts are characterized by a
      significant increase in cardiac fibrosis. However, the contribution of the
      proteolytic/antiproteolytic system in aortic stenosis (AS) during hypertrophy
      progression has not yet been elucidated. METHODS: Three groups of AS patients (I:
      EF >50%, n = 12; II: EF 50% to 30%, n = 10; III: EF <30%, n = 12) undergoing
      aortic valve replacement and seven controls were studied. Tissue samples were
      investigated by immunoconfocal microscopy, Western blotting, and zymography.
      RESULTS: Quantitative analysis by immunoconfocal microscopy and Western blotting
      showed an upregulation of MMP-1, -2, -3, -9, -13, and -14 in group I and further
      increases in later stages. Tissue inhibitors of metalloproteinase-1 and -2 were
      enhanced and TIMP-4 was decreased in comparison to control. Gelatinolytic
      activity of MMP-2 significantly (p < 0.05) increased 1.2-fold (group I), 1.5-fold
      (group II), and 1.6-fold (group III) over control. The level of collagen I was
      significantly upregulated in all AS groups. Immunoconfocal microscopy showed that
      MMPs and TIMPs are produced predominantly by fibroblasts. The number of
      proliferating fibroblasts was significantly elevated during the transition to HF
      (0.67 n/mm(2)-control, 5.03-group III, p < 0.05). CONCLUSIONS: In human hearts a
      continuous turnover of the extracellular matrix occurs during the progression
      from compensated hypertrophy to HF that is characterized by the upregulation of
      MMPs and inadequate inhibition by TIMPs. The altered balance between
      proteolysis/antiproteolysis with accompanying proliferation of fibroblasts
      results in fibrosis progression.

PMID- 15489094
TI  - A mechanism for immediate reduction in mitral regurgitation after cardiac
      resynchronization therapy: insights from mechanical activation strain mapping.
AB  - OBJECTIVES: We tested the hypothesis that an immediate reduction in mitral
      regurgitation (MR) after cardiac resynchronization therapy (CRT) results from
      improved coordinated timing of the papillary muscle insertion sites, using the
      novel approach of mechanical activation strain mapping. BACKGROUND: Heart failure
      patients with left bundle branch block often benefit acutely from CRT; however,
      the role and mechanism of reduction of MR are unclear. METHODS: Twenty-six
      consecutive patients undergoing CRT with at least mild MR were studied (ejection
      fraction 24 +/- 6%; QRS duration 168 +/- 30 ms). Echocardiographic Doppler and
      strain imaging was performed immediately before and the day after CRT, as well as
      in 10 normal control subjects. Mechanical activation sequence maps were
      constructed using longitudinal strain from 12 basal and mid-LV sites, with color
      coding of time-to-peak strain. RESULTS: Mitral regurgitation by the volumetric
      method consistently decreased after CRT: regurgitant volume from 40 +/- 20 ml to
      24 +/- 17 ml and regurgitant fraction from 40 +/- 12% to 25 +/- 14% (both: p <
      0.001 vs. baseline). Normal controls had uniform segmental time-to-peak strain,
      with a difference of only 12 +/- 8 ms between all segments. In contrast, CRT
      patients at baseline had a 106 +/- 74 ms time delay between papillary muscle
      insertion sites (p < 0.001 vs. normal). This interpapillary muscle time delay
      shortened after CRT to 39 +/- 43 ms (p < 0.001 vs. baseline) and was
      significantly correlated with reductions in mitral regurgitant fraction (r =
      0.77, p < 0.001). CONCLUSIONS: Cardiac resynchronization therapy significantly
      and immediately reduced MR. Improved coordinated timing of mechanical activation
      of papillary muscle insertion sites appears to be a mechanistic contributor to
      immediate MR reduction by CRT.

PMID- 15489095
TI  - The electrocardiogram during sinus rhythm and tachycardia in patients with Mahaim
      fibers: the importance of an "rS" pattern in lead III.
AB  - OBJECTIVES: The purpose of the study was to identify the electrocardiographic
      (ECG) characteristics of the Mahaim fiber. BACKGROUND: Mahaim fibers are slowly
      conducting accessory pathways reaching into the right ventricle. They often play
      a role in tachycardias. METHODS: We retrospectively analyzed 40 patients with
      Mahaim fibers. Five patients had associated Wolff-Parkinson-White syndrome and
      were excluded from the study. Two patients had a short atrioventricular
      decremental accessory pathway and were also excluded. The remaining 33 patients
      had a tachycardia with anterograde conduction over a Mahaim fiber. Twenty were
      female. Their mean age was 24 +/- 10 years. RESULTS: The most common pattern of
      minimal preexcitation during sinus rhythm was an rS pattern in lead III. This was
      found in 20 patients. There was a match between the presence of rS in lead III
      during sinus rhythm and left axis deviation during tachycardia with anterograde
      conduction over the Mahaim fiber. After ablation, a different QRS pattern emerged
      in lead III, indicating the absence of conduction over the Mahaim fiber. To
      obtain information on the prevalence of an rS pattern in lead III in age-matched
      controls with palpitations and without structural heart disease, the 12-lead ECG
      of 200 young individuals were examined. An rS pattern in lead III was found in
      6%. CONCLUSIONS: A narrow QRS with an rS pattern in lead III during sinus rhythm
      in a patient with a history of palpitations should alert the physician to the
      possibility of a Mahaim fiber. During tachycardia, these patients typically show
      a left bundle branch block-like QRS complex with left axis deviation.

PMID- 15489096
TI  - Flow-mediated vasodilation and the risk of developing hypertension in healthy
      postmenopausal women.
AB  - OBJECTIVES: This study provided the opportunity to assess the relationship
      between endothelial vasomotor function and incidence of hypertension in a cohort
      of postmenopausal women. BACKGROUND: Both menopause and hypertension are
      associated with endothelial dysfunction and are well-known risk factors for
      atherosclerotic-related disease. METHODS: We conducted a prospective cohort study
      that began in 1996 on 952 apparently healthy postmenopausal women, age 53 +/- 5
      years (range 44 to 60 years), with initially normal levels of blood pressure and
      no history of hypertension. All participants were followed up for a mean period
      of 3.6 +/- 0.7 years (range 0.5 to 6.9 years). Endothelial function was measured
      as flow-mediated dilation of the brachial artery using high-resolution
      ultrasound. RESULTS: During follow-up 112 women developed hypertension. The
      adjusted relative risk for women with flow-mediated dilation of 3.5 or less
      (lowest quartile) was 5.77 (95% confidence interval 4.34 to 8.10) versus women
      with flow-mediated dilation of 5.5 or greater (highest quartile, referent). Each
      one-unit decrease of flow-mediated dilation was associated with a significant 16%
      (95% confidence interval 12% to 33%) increase in the multiple-adjusted relative
      risk of incident hypertension. CONCLUSIONS: These prospective data indicate a
      significant increase in the relative risk of hypertension with each unit decrease
      of flow-mediated dilation that is independent of age and baseline systolic and
      diastolic pressure values. This could suggest that an impaired endothelial
      vasomotor function precedes and predicts the future development of hypertension
      in postmenopausal women.

PMID- 15489097
TI  - Risk factors for aortic complications in adults with coarctation of the aorta.
AB  - OBJECTIVES: We sought to determine the prevalence and predisposing condition for
      aortic wall complications in adults with either repaired or non-repaired
      coarctation of the aorta. BACKGROUND: Aortic wall complications may develop in
      adults with coarctation of the aorta, despite successful surgical repair in
      childhood. METHODS: A total of 235 adults with coarctation (mean age 27 +/- 13
      years) were retrospectively reviewed. Treatment had been performed by surgery in
      181 patients (group I) or by balloon angioplasty or stenting in 28 patients
      (group II). No previous intervention had been carried out in 26 patients with
      mild coarctation at diagnosis (group III). RESULTS: Forty-four aortic wall
      complications were found in 37 patients (16%). There were no differences among
      the three groups with respect to total complications (15%, 18%, and 15%,
      respectively), ascending aortic aneurysms (9%, 11%, and 12%), or descending
      aortic aneurysms (4% in all three groups). Multivariate analysis did not show a
      significant relationship between previous repair, type of repair, age at repair,
      residual Doppler pressure gradient, or systemic hypertension and the occurrence
      of aortic complications. Only aging (risk ratio [RR] 1.4 per decade of age, 95%
      confidence interval [CI] 1.1 to 1.8, p = 0.002) and bicuspid aortic valve (RR
      3.2, 95% CI 1.3 to 7.5, p = 0.005) were significantly related to these
      complications. CONCLUSIONS: Aortic wall complications are frequent in adults with
      coarctation of the aorta beyond that attributable to associated hemodynamic
      derangement or previous repair. The only independent risk factors appear to be
      advanced age and bicuspid aortic valve.

PMID- 15489098
TI  - Morphology of bicuspid aortic valve in children and adolescents.
AB  - OBJECTIVES: The aim of this study was to determine the relationship between
      aortic valve morphology and valve dysfunction. BACKGROUND: The morphology of the
      bicuspid or bicommissural aortic valve (BAV) may predict the severity of valve
      dysfunction. Therefore, we assessed the relationship between BAV, aortic
      coarctation, and the degree of valve pathology in children. METHODS: A
      retrospective review of 1,135 patients with BAV who were identified between 1986
      and 1999 was performed. Patients younger than 18 years of age with BAV that was
      identifiable via echocardiography were included. The most recent or last study of
      each patient before intervention or endocarditis was reviewed. Mild stenosis was
      defined as a valve gradient > or =2 m/s, moderate or greater aortic stenosis as >
      or =3.5 m/s. Aortic regurgitation was quantified using standard criteria.
      RESULTS: Median age was 3 years (range, 1 day to 17.9 years), and 67% of the
      patients were male. Right-coronary and left-coronary leaflet fusion were the most
      common types of BAV (70%). Aortic stenosis that was moderate or greater was
      observed most often in patients with right-coronary and non-coronary leaflet
      fusion (odds ratio 2.4, 95% confidence interval 1.6 to 3.6; p < or = 0.001).
      Similarly, right-coronary and non-coronary leaflet fusion was more often
      associated with moderate aortic regurgitation or greater (odds ratio 2.4, 95%
      confidence interval 1.2 to 4.7; p = 0.01). The majority of patients with aortic
      coarctation had fusion of the right-coronary and left-coronary leaflets (89%),
      and aortic coarctation was associated with lesser degrees of valve stenosis or
      regurgitation. CONCLUSIONS: Analysis of BAV morphology is of clinical and
      prognostic relevance. Fusion of the right-coronary and non-coronary leaflets was
      associated with more significant valve pathology, whereas fusion of the right
      coronary and left-coronary leaflets was associated overwhelmingly with aortic
      coarctation and less aortic valve pathology.

PMID- 15489099
TI  - Acute and chronic reduction of functional mitral regurgitation in experimental
      heart failure by percutaneous mitral annuloplasty.
AB  - OBJECTIVES: We sought to determine acute and chronic efficacy of a percutaneous
      mitral annuloplasty (PMA) device in experimental heart failure (HF). Further, we
      evaluated the potential for adverse effects on left ventricular (LV) function and
      coronary perfusion. BACKGROUND: Reduction of mitral annular dimension with a PMA
      device in the coronary sinus may reduce functional mitral regurgitation (MR) in
      advanced HF. METHODS: Study 1: a PMA device was placed acutely in anesthetized
      open-chest dogs with rapid pacing-induced HF (n = 6) instrumented for pressure
      volume analysis. Study 2: in 12 anesthetized dogs with HF, fluoroscopic-guided
      PMA was performed, and dogs were followed for four weeks with continuing rapid
      pacing. RESULTS: Study 1: percutaneous mitral annuloplasty reduced annular
      dimension and severity of MR at baseline and with phenylephrine infusion to
      increase afterload (MR jet/left atrial [LA] area 26 +/- 1% to 7 +/- 2%, p <
      0.05). Pressure volume analysis demonstrated no acute impairment of LV function.
      Study 2: no device was placed in two dogs because of prototype size limitations.
      Attempted PMA impaired coronary flow in three dogs. Percutaneous mitral
      annuloplasty (n = 7) acutely reduced MR (MR jet/LA area 43 +/- 4% to 8 +/- 5%, p
      < 0.0001), regurgitant volume (14.7 +/- 2.1 ml to 3.1 +/- 0.5 ml, p < 0.05),
      effective regurgitant orifice area (0.130 +/- 0.010 cm(2) to 0.040 +/- 0.003
      cm(2), p < 0.05), and angiographic MR grade (2.8 +/- 0.3 device to 1.0 +/- 0.3
      device, p < 0.001). In the conscious state, MR was reduced at four weeks after
      PMA (MR jet/LA area 33 +/- 3% HF baseline vs. 11 +/- 4% four weeks after device,
      p < 0.05) CONCLUSIONS: Percutaneous mitral annuloplasty results in acute and
      chronic reduction of functional MR in experimental HF.

PMID- 15489100
TI  - Percutaneous valve replacement and repair: fiction or reality?

PMID- 15489101
TI  - Strain echocardiography tracks dobutamine-induced decrease in regional myocardial
      perfusion in nonocclusive coronary stenosis.
AB  - OBJECTIVES: This study was designed to determine whether strain echocardiography
      parameters reflect changes in regional myocardial perfusion during dobutamine
      stress. BACKGROUND: Strain echocardiography depicts regional myocardial
      mechanical activity. Ischemia has been shown to reduce systolic strain rate (sSR)
      and prolong the time to regional lengthening (T(RL)). In an experimental model,
      we tested whether sSR and T(RL) tracked dobutamine-induced changes in regional
      myocardial perfusion (regional myocardial blood flow [RMBF]), as measured by
      colored microspheres. METHODS: We used a closed-chest pig model of nonocclusive
      coronary stenosis (n = 14) created by inflating an angioplasty balloon in the
      proximal left anterior descending artery. Invasive hemodynamics, RMBF, and strain
      parameters were measured at baseline and peak dobutamine stimulation before and
      during the coronary stenosis. We compared segments with reduced RMBF versus those
      with preserved RMBF at peak dobutamine stimulation. RESULTS: Peak sSR correlated
      with RMBF (r = 0.70). In the absence of coronary stenosis, dobutamine stimulation
      caused a significant increase in RMBF and sSR and a decrease in T(RL). This
      response was blunted during coronary stenosis. Using the "best cutoff" method,
      the sensitivity and specificity for prediction of reduced RMBF (ischemia) was 81%
      and 91% for sSR and 65% and 91% for T(RL), respectively. These changes occurred
      in the absence of any change in global systolic and diastolic function
      (dP/dT(max), dP/dT(min), and tau). CONCLUSIONS: Novel strain parameters that
      depict regional myocardial mechanics are able to predict changes in RMBF during
      dobutamine stress. Quantitative strain parameters may complement current
      echocardiographic techniques for ischemia detection and potentially improve the
      accuracy and reproducibility of stress echocardiography.

PMID- 15489102
TI  - Do regional deformation indexes reflect regional perfusion in all ischemic
      substrates?

PMID- 15489103
TI  - Ephedrine increases ventricular arrhythmias in conscious dogs after myocardial
      infarction.
AB  - OBJECTIVES: This study examined the hypothesis that the sympathomimetic activity
      of ephedrine increases the risk of lethal arrhythmias. BACKGROUND: The
      sympathomimetic amine, ephedrine, is used to augment physical performance and as
      a weight loss aid, but little is known about the cardiovascular consequences in
      individuals with ischemic heart disease. METHODS: Fifteen dogs at low risk for
      ventricular fibrillation (VF) during exercise and transient myocardial ischemia
      30 days after a small anterior myocardial infarction were retested after five
      days of ephedrine use (Xenadrine, 0.4 mg/kg/day orally). To assess the effects of
      ephedrine on cardiac autonomic control, baroreceptor reflex sensitivity (BRS),
      heart rate (HR) variability, HR response to acute myocardial ischemia, and
      resting catecholamines were measured before and after ephedrine. Dogs were used
      as their own control when possible. RESULTS: Nine of 15 animals had increased
      ventricular arrhythmias during ephedrine treatment (p = 0.01) and four had VF.
      Three dogs that had VF could not be resuscitated. Five animals with increased
      arrhythmias during ephedrine treatment had none during a third exercise and
      ischemia test after drug washout. Heart rates were higher after 30 s of
      myocardial ischemia during ephedrine treatment (204 +/- 25 beats/min no drug vs.
      218 +/- 26 beats/min with ephedrine, p = 0.03). All plasma catecholamines
      increased after ephedrine administration. No changes in BRS, HR variability, or
      exercise HR were noted. CONCLUSIONS: Ephedrine increases ischemia-dependent
      arrhythmias at doses recommended in over-the-counter preparations. Increased
      arrhythmia risk was associated with augmented ischemia-dependent sympathetic
      reflex activation.

PMID- 15489104
TI  - p38 mitogen-activated protein kinase inhibition improves cardiac function and
      attenuates left ventricular remodeling following myocardial infarction in the
      rat.
AB  - OBJECTIVES: The aim of this study was to examine the effect of the p38 mitogen
      activated protein kinase (MAPK) inhibitor, RWJ-67657 (RWJ), on left ventricular
      (LV) dysfunction and remodeling post-myocardial infarction (MI) in rats.
      BACKGROUND: p38 MAPK signaling has been implicated in the progression of chronic
      heart failure. METHODS: From day 7 post-MI (coronary artery ligation), rats
      received either RWJ (50 mg/day, by gavage, n = 8, MI+RWJ) or vehicle (by gavage,
      n = 8, MI+V) for 21 days. Echocardiography was performed on day 6, before the
      commencement of treatment, and on day 27. In vivo hemodynamic measurements were
      made on day 28. Sham-operated rats served as controls. RESULTS: The LV end
      diastolic pressure and lung/body weight ratio were reduced, whereas the maximum
      rate of rise of LV pressure was increased towards sham levels in MI+RWJ compared
      with MI+V. Baseline echocardiographic studies demonstrated uniform LV remodeling
      and dysfunction in MI rats. Fractional shortening (FS) further deteriorated in
      MI+V, whereas FS was preserved in MI+RWJ. Progressive LV dilation and infarct
      expansion observed in MI+V were inhibited in MI+RWJ. MI+RWJ also demonstrated
      increased myocyte hypertrophy in the peri-infarct and non-infarct zones, and
      reduced myocardial collagen and alpha-smooth muscle actin (SMA) immunoreactivity
      compared with MI+V. The antifibrotic effects of RWJ in vivo may reflect direct
      effects on cardiac fibroblasts, because RWJ attenuated transforming growth factor
      beta-1-stimulated collagen synthesis and alpha-SMA expression in isolated cardiac
      fibroblasts. RWJ also protected cultured myocytes from hydrogen peroxide-induced
      apoptosis. CONCLUSIONS: RWJ-67657 treatment post-MI had beneficial effects on LV
      remodeling and dysfunction, supporting a key role for p38 MAPK in pathologic cell
      signaling in these processes and its inhibition as a novel therapy.

PMID- 15489105
TI  - Transplantation of progenitor cells and regeneration enhancement in acute
      myocardial infarction: final one-year results of the TOPCARE-AMI Trial.
AB  - OBJECTIVES: The Transplantation of Progenitor Cells And Regeneration Enhancement
      in Acute Myocardial Infarction (TOPCARE-AMI) trial investigates both safety,
      feasibility, and potential effects on parameters of myocardial function of
      intracoronary infusion of either circulating progenitor cells (CPC) or bone
      marrow-derived progenitor cells (BMC) in patients with acute myocardial
      infarction (AMI). BACKGROUND: In animal experiments, therapy with adult
      progenitor cells was shown to improve vascularization, left ventricular (LV)
      remodeling, and contractility after AMI. METHODS: A total of 59 patients with AMI
      were randomly assigned to receive either CPC (n = 30) or BMC (n = 29) into the
      infarct artery at 4.9 +/- 1.5 days after AMI. RESULTS: Intracoronary progenitor
      cell application did not incur any measurable ischemic myocardial damage, but one
      patient experienced distal embolization before cell therapy. During hospital
      follow-up, one patient in each cell group developed myocardial infarction; one of
      these patients died of cardiogenic shock. No further cardiovascular events,
      including ventricular arrhythmias or syncope, occurred during one-year follow-up.
      By quantitative LV angiography at four months, LV ejection fraction (EF)
      significantly increased (50 +/- 10% to 58 +/- 10%; p < 0.001), and end-systolic
      volumes significantly decreased (54 +/- 19 ml to 44 +/- 20 ml; p < 0.001),
      without differences between the two cell groups. Contrast-enhanced magnetic
      resonance imaging after one year revealed an increased EF (p < 0.001), reduced
      infarct size (p < 0.001), and absence of reactive hypertrophy, suggesting
      functional regeneration of the infarcted ventricles. CONCLUSIONS: Intracoronary
      infusion of progenitor cells (either BMC or CPC) is safe and feasible in patients
      after AMI successfully revascularized by stent implantation. Both the excellent
      safety profile and the observed favorable effects on LV remodeling, provide the
      rationale for larger randomized double-blind trials.

PMID- 15489106
TI  - Mapping and ablation of polymorphic ventricular tachycardia after myocardial
      infarction.
AB  - OBJECTIVES: The goal of this study was to describe the mapping and ablation of
      polymorphic ventricular tachycardia (VT) after myocardial infarction (MI).
      BACKGROUND: The initiating mechanisms of polymorphic VT after MI have not been
      reported. METHODS: Five patients (four males; age 61 +/- 7 years) with recurrent
      episodes of polymorphic VT after anterior MI (left ventricular ejection fraction
      32 +/- 7%) despite revascularization and antiarrhythmic drugs were studied. All
      patients demonstrated frequent ventricular premature beats (PBs) initiating
      polymorphic VT. Pace mapping and activation mapping were used to identify the
      earliest site of PB activity. The presence of a Purkinje potential preceding PB
      defined its origin from the Purkinje network. Electroanatomic voltage mapping was
      performed to delineate the extent of MI. RESULTS: The PBs were observed in all
      cases to arise from the Purkinje arborization in the MI border zone. These PBs
      were right bundle-branch block in all five patients, with morphologic variations
      in the limb leads in four; one also had a left bundle-branch block morphology.
      The coupling interval of the PB to the preceding QRS complex demonstrated
      significant variations (320 to 600 ms). During PB, the Purkinje potential at the
      same site preceded the QRS complex by 20 to 160 ms and was associated with
      different morphologies. Repetitive Purkinje activity was documented during
      polymorphic VT. Splitting of Purkinje activity and Purkinje to muscle conduction
      block were also observed. Ablation at these sites eliminated all PBs. At 16 +/- 5
      months follow-up using defibrillator memory interrogation, no patient has had
      recurrence of arrhythmia. CONCLUSIONS: The Purkinje arborization along the border
      zone of scar has an important role in the mechanism of polymorphic VT in patients
      after MI. Ablation of the local Purkinje network allows suppression of
      polymorphic VT.

PMID- 15489107
TI  - Publication bias and journals as policemen.

PMID- 15489108
TI  - President's page: The trust imperative: ethical choice always puts patient first.

PMID- 15489109
TI  - Thrombus formation on intracardiac devices: a complex issue.

PMID- 15489110
TI  - Risk of thrombus formation on devices used to close transcatheter atrial septal
      defect and patent foramen ovale.

PMID- 15489111
TI  - Transcatheter intracardiac device implantation for atrial level defects and
      thrombosis: a call for randomized, controlled data.

PMID- 15489113
TI  - Incidence and clinical course of thrombus formation on atrial septal defect and
      patent foramen ovale closure devices.

PMID- 15489114
TI  - Cardiovascular professionalism and ethics in the modern era.

PMID- 15489115
TI  - Task force 1: The ACCF and AHA codes of conduct in human subjects research.

PMID- 15489116
TI  - Task force 2: Investigator participation in clinical research.

PMID- 15489117
TI  - Task force 3: Disclosure of relationships with commercial interests: policy for
      educational activities and publications.

PMID- 15489118
TI  - Task force 4: Appropriate clinical care and issues of "self-referral".

PMID- 15489119
TI  - Task force 5: Expert testimony and opinions.

PMID- 15489120
TI  - Task force 6: Code of conduct for staff and volunteer leadership.

PMID- 15489121
TI  - Tertiary selenoamide compounds are useful superoxide radical scavengers in vitro.
AB  - We investigated the scavenging effects of tertiary selenoamide compounds for
      super oxide radicals using a highly sensitive and quantitative chemiluminescence
      method. At 333 nM, tertiary selenoamide compounds scavenged 25.8-81.6% of O(2)(
      ). N-(Phenylselenocarbonyl) piperidine was the most effective scavenger of
      superoxide radicals. While N,N-diethyl-2-selenonaphthylamide and N,N-diethyl-4
      chloroselenobenzamide was a moderately effective scavenger of superoxide
      radicals. The IC(50) of N-(phenylselenocarbonyl) piperidine and N,N-diethyl-2
      selenonaphthylamide were determined to be 110 and 182 nM, respectively. The
      results suggest that tertiary selenoamide compounds are useful scavengers of
      superoxide radicals.

PMID- 15489122
TI  - Pharmacokinetics of levosimendan and its active metabolite OR-1896 in rapid and
      slow acetylators.
AB  - OBJECTIVE: The purpose of this study was to investigate the pharmacokinetics of
      levosimendan and to determine the primary pharmacokinetic parameters of the
      pharmacologically active metabolite OR-1896 in rapid and slow acetylators.
      METHODS: Levosimendan was administered as a constant rate (0.1 microg/(kg min))
      i.v. infusion for 24h in six rapid and six slow acetylators based on N
      acetyltransferase 2 genotyping. At the end of the infusion, a small amount (2.5
      microg/kg) of (13)C-labeled OR-1896 was administered by i.v. infusion for 10 min.
      Blood samples were taken at predefined sampling points 14 days post-infusion and
      levosimendan and its metabolite concentrations were determined by LC-MS/MS.
      RESULTS: Steady-state concentrations of levosimendan were achieved within 4-8h
      and no differences were found in the pharmacokinetics of the parent compound
      between the rapid and slow acetylators. The maximum concentrations of amino
      phenylpyridazinone metabolite OR-1855 and N-acetylated conjugate OR-1896 were
      observed approximately 24h after terminating the infusion. AUC of OR-1896 was
      approximately 3.5 times higher in the rapid acetylators compared to the slow
      acetylators (P = 0.002, 95% confidence interval for group ratio from 2.0 to 8.2).
      The mean +/- S.D. fraction of levosimendan metabolized to OR-1896 was 6.8 +/-
      2.8% in the rapid and 4.3 +/- 2.4% in the slow acetylators (P = 0.12). (13)C-OR
      1855 concentrations were detected in plasma after administration of (13)C-OR-1896
      indicating deacetylation from OR-1896 to OR-1855. CONCLUSIONS: Plasma OR-1896
      levels during and after levosimendan treatment are dependent on the acetylation
      status of the subject-rapid acetylators having 3.5 times higher concentrations
      than slow acetylators.

PMID- 15489123
TI  - Permeability through DOPC/dodecane membranes: measurement and LFER modelling.
AB  - The permeabilities of 43 ionisable compounds through membranes consisting of 2%
      dioleylphosphatidylcholine (DOPC) in dodecane at pH values between 3 and 10 have
      been measured. The observed values are corrected for the effects of ionisation
      and diffusion through the unstirred water layer in order to obtain estimates of
      intrinsic permeability. The intrinsic permeabilities are modelled using Abraham's
      linear free energy relation method. This not only provides a predictive model of
      membrane permeability, but also reveals the factors determining passive
      permeation through membranes made from 2% DOPC in dodecane. Hydrogen bonding
      dominates, acting to strongly inhibit permeation, polarity/polarisability effects
      are less important, and size acts to enhance permeation.

PMID- 15489124
TI  - Comparison of cannabinoid ligands affinities and efficacies in murine tissues and
      in transfected cells expressing human recombinant cannabinoid receptors.
AB  - Affinities and efficacies of several reference cannabinoid ligands were
      investigated at central and peripheral cannabinoid receptors in three different
      species (rat, mouse, and human). The tested compounds belong to different
      chemical classes such as classical and non-classical terpene derivatives
      (Delta(8)-THC, Delta(9)-THC, HU 210, CP 55,940, CP 55,244, CP 55,243 and CP
      47,947), aminoalkylindole (WIN 55,212-2, WIN 55,212-3) and diarylpyrazole
      cannabinoids (SR 141716A, SR 144528). As cannabinoid receptors have been shown to
      be mainly coupled to Gi/o type G- proteins, and by using the [(35)S]-GTPgammaS
      nucleotide binding modulation, we characterized the functional activity of these
      ligands which can act as agonists (positive intrinsic activity), partial agonists
      (partial positive intrinsic activity), antagonists (no intrinsic activity), or
      inverse agonists (negative intrinsic activity). To our knowledge, some
      derivatives (Delta(8)-THC, WIN 55,212-3, CP 55,243 and CP 47,947) have never been
      characterized in [(35)S]-GTPgammaS binding assays and up to now, this study
      represents the largest survey of reference cannabinoids performed in unique
      experimental conditions and in the same laboratory.

PMID- 15489125
TI  - Albumin loaded microsphere of amphiphilic poly(ethylene glycol)/ poly(alpha
      ester) multiblock copolymer.
AB  - The purpose of this study is to investigate the microspheres (MS) based on
      (AB)(n) type amphiphilic multiblock copolymers for sustained and complete release
      of a model protein, bovine serum albumin (BSA). The MS were prepared by a
      modified water-in-oil-in-water (W/O/W) double emulsion method using amphiphilic
      multiblock copolymers consisting of poly(ethylene glycol) (PEG) and a poly(alpha
      ester), poly(epsilon-caprolactone) (PCL) or poly(l-lactic acid) (PLLA). The size
      of MS and encapsulation efficiency of BSA within MS were not noticeably
      influenced by the copolymer composition used in this experiment. While BSA was
      completely released from PEG/PLLA MS through matrix erosion and the diffusion of
      BSA, it was released only to an extent of 60% from PEG/PCL MS solely through the
      diffusion process. However, the release of BSA from PEG/PCL MS dramatically
      increased and then reached 100% release in 10 days after thermal treatment of the
      MS at 50 degrees C for 30 min in the middle of release test (on day 15).

PMID- 15489126
TI  - A concentric cylinder shear device for the study of stability in intravenous
      emulsions.
AB  - This paper introduces the use of a concentric cylinder shear device for studying
      the stability of intravenous emulsions under shear, and examines the relationship
      between shearing conditions and the emulsion droplet size and distribution, as
      characterised by laser diffraction and optical counting. Theoretically, the
      device generated flow in the Taylor region, but a linear relationship between the
      natural log mean droplet diameter and time, which was observed at all shear
      rates, suggested that coalescence kinetics could be treated in a manner analogous
      to laminar flow. An order of magnitude increase in coalescence rate was achieved
      within the shear rate range examined (2802-6164 s(-1)), yet irrespective of shear
      rate, the particle size distribution evolved a similar multi-peak pattern with
      common secondary peaks at 1.8 and 3.8 microm. This pattern was similar to that
      observed during shake testing of the emulsion. In emulsions destabilised with
      increasing concentrations of NaCl, a shear-dependent threshold was observed above
      which there was a marked increase in coalescence. This threshold behaviour also
      occurred on shake testing, and it appears to be analogous to the critical
      coagulation concentration observed when shear testing of suspension. The
      concentric cylinder device allows a variable shear rate to be applied in a
      precise and controlled way and therefore represents an advance over shake
      testing. Emulsions of differing stability may be examined, and the technique has
      application in the study of emulsion behaviour and stability under shear, and
      potentially in accelerated stability studies.

PMID- 15489127
TI  - The characteristics of spontaneously forming physically cross-linked hydrogels
      composed of two water-soluble phospholipid polymers for oral drug delivery
      carrier I: hydrogel dissolution and insulin release under neutral pH condition.
AB  - Hydrogels bearing a phospholipid polar group, 2-methacryloyloxyethyl
      phosphorylcholine (MPC), were prepared from two aqueous solutions of polymers,
      water-soluble poly[MPC-co-methacrylic acid (MA)] (PMA) and poly[MPC-co-n-butyl
      methacrylate (BMA)] (PMB). The hydrogel, which was formed by physical cross
      linking spontaneously without any chemical reactions and/or any physical stimuli,
      showed a controllable insulin release through a pH change in the medium by
      changing the hydrogen bonds. In this study, the mechanical strength, erosion of
      the hydrogel caused by polymer dissociation, and the release of insulin were
      examined with attention to the following three parameters of the MPC polymer:
      molecular weight of the polymers, composition of PMA and PMB (PMA/PMB ratio), and
      polymer concentration inside the hydrogel. The hydrogel with the highest
      mechanical strength was obtained at a PMA/PMB ratio = 3/7 (v/v, by volume ratio)
      while the hydrogel with the slowest dissolution was obtained at a ratio of 5/5
      (v/v). The release was in good match with the dissolution and followed anomalous
      transport for all, but the diffusion exponent n changed according to the PMA/PMB
      ratio. An increase in the polymer concentration inside the hydrogel caused an
      increase in the mechanical strength of the hydrogel. When the polymer
      concentration was more than 20 wt.%, the absorption of water under neutral pH
      condition (pH 6.8) was observed. The release of insulin was suppressed below 10%
      during the swelling process of the hydrogel under neutral pH condition, while
      release was accelerated during the erosion process of the hydrogel. The
      relationship between erosion of the hydrogel and the release of the insulin
      depended on the erosion process of the hydrogel but differed according to the
      PMA/PMB ratio.

PMID- 15489128
TI  - Choice of rotation speed (rpm) for bio-relevant drug dissolution testing using a
      crescent-shaped spindle.
AB  - Recently a new crescent-shaped spindle has been proposed to address the issues
      related to poor hydrodynamics of the USP paddle apparatus and its associated
      artifacts of high variability and lack of bio-relevant results. For improved
      comparison of drug dissolution characterization, it is highly desirable to
      conduct testing using common experimental conditions such as spindle rotation
      speed. A study was conducted in which different products were tested using the
      crescent-shaped spindle to propose a common rpm speed for improved comparative
      drug dissolution testing. Conventional- (200 mg) and extended-release (200 and
      400 mg) carbamazepine tablets of multiple brands and amoxicillin capsules (250
      and 500 mg) were analysed using the crescent- shaped spindle at 25, 50 and/or 75
      rpm. Drug release was evaluated for 1.5h for amoxicillin and for 3.0 and 24h for
      conventional- and extended-release carbamazepine tablets products respectively.
      The dissolution media used were 0.05 M phosphate buffer for amoxicillin capsules
      and water containing 0.5% sodium lauryl sulphate for carbamazepine tablet
      products. All products showed characteristic drug release profiles, reflecting
      the fast and slow drug release natures of the products tested with complete drug
      release within expected time durations. Based on an expected maximum drug release
      criterion of 85% in a reasonable time, at a relatively slow drug release rate and
      within a dosing interval, a spindle speed of 25 rpm was found to be the most
      appropriate. Thus, it is concluded that drug products can be analysed using a
      single spindle type (crescent) with a single rpm (25) which would, not only
      result in simpler dissolution procedures, but also provide enhanced efficiencies
      from economical and regulatory aspects.

PMID- 15489129
TI  - Isoproterenol-induced myocardial infarction in rabbits. Protection by propranolol
      or labetalol: a proposed non-invasive procedure.
AB  - Myocardial infarction is usually induced in small animals by means of invasive
      techniques based on mechanical coronary obstruction. As it has been reported that
      isoproterenol can cause ischemic myocardial alterations, lipid peroxide
      generation and procoagulant activity, we administered it to rabbits in order to
      induce a non-invasive myocardial infarction associated with above mentioned
      cardiovascular risk factors. Considerable ischemic alterations were observed in
      the animals treated with isoproterenol, including areas of myocardial necrosis,
      contraction band necrosis, increased plasma levels of cardiac necrosis markers (c
      troponin I and myoglobin), and electrocardiographic modifications (ST segment
      changes and T wave inversion). The myocardial infarction was attributed to the
      inotropic activity of isoproterenol leading to intracellular calcium overload.
      The cardiac necrosis phenomena appear to be associated with isoproterenol-induced
      lipid peroxide generation (as shown by the decrease in plasma Vitamin E levels)
      and increased procoagulant activity (a shortened PTT). As this model of
      myocardial damage is based on the use of beta-stimulatory isoproterenol, the beta
      blockers propranolol and labetalol were administered to isoproterenol-treated
      animals. Pretreatment with propranolol or labetalol counteracted the appearance
      of the myocardial histological alterations and the associated ECG and biochemical
      lesions. This protective activity was attributed to the beta-blockade. The
      results of this study demonstrate that myocardial infarction can be induced
      chemically and non-invasively in small laboratory animals. The procedure is
      proposed for the study of early ischemic myocardial lesions and the screening of
      drugs (such as beta-blockers) that can prevent myocardial necrosis damage and the
      associated risk factors.

PMID- 15489130
TI  - Solubilisation of poorly water-soluble drugs during in vitro lipolysis of medium-
      and long-chain triacylglycerols.
AB  - The partitioning of poorly soluble drugs into an aqueous micellar phase was
      exploited using an in vitro lipid digestion model, simulating the events taking
      place during digestion of acylglycerols in the duodenum. The aqueous micellar
      phase was isolated after ultracentrifugation of samples obtained at different
      degrees of triacylglycerol hydrolysis. Flupentixol, 1'-[4-[1-(4-fluorophenyl)-1-H
      indol-3-yl]-1-butyl]spiro[iso-benzofuran-1(3H), 4' piperidine] (LU 28-179) and
      probucol were studied. The effect of the alkyl chain length of the
      triacylglycerol was studied using a medium-chain triacylglycerol (MCT) and a long
      chain triacylglycerol (LCT), respectively. In general, an oil solution was used
      as the lipid source in the model. Samples were analysed in regard to micellar
      size, lipid composition and drug concentration. During lipolysis, the content of
      lipolytic products in the aqueous micellar phase increased. The micellar size
      (R(H) approximately 3 nm) only increased when long-chain lipolytic products were
      incorporated in the mixed micelles (R(H) approximately 7.8 nm). Flupentixol was
      quickly transferred to the mixed micelles due to high solubility in this phase
      (100% released). A tendency towards higher solubilisation of LU 28-179, when it
      was administered in the LCT (approximately 24% released) compared to when it was
      administered in the MCT (approximately 15% released) at 70% hydrolysis, and a
      lagphase was observed. There was no difference in the solubilisation of probucol
      using MCT or LCT ( approximately 20% released), respectively. Differences in the
      physicochemical properties of the drugs resulted in differences in their
      distribution between the phases arising during lipolysis.

PMID- 15489131
TI  - Modern criteria to establish human cancer etiology.

PMID- 15489132
TI  - Multistep and multifactorial carcinogenesis: when does a contributing factor
      become a carcinogen?
AB  - Our greatest successes in fighting cancer derive from the identification and
      removal or inactivation of carcinogenic substances, and from the identification
      and removal of pre-malignant lesions. In comparison, our successes at treating
      already formed malignancies have been minimal. Therefore, emphasis should be put
      in identifying and removing pre-malignant lesions, and in the identification and
      removal of those agents that cause or contribute to cancer development. It is
      important to target initiators, co-carcinogens and promoters, since by removing
      any one of them, tumor growth may be prevented. Identification of these agents is
      difficult. Epidemiological studies largely study cancer after it has occurred. It
      would be preferable to identify potential carcinogenic substances at an earlier
      stage before they have caused a large number of malignancies and thus become
      identifiable by epidemiology. During the past three decades, we have accumulated
      an impressive amount of evidence concerning molecular pathways that when altered
      contribute to malignant growth. It is time that we start applying this knowledge
      to the identification of human carcinogens. Here, we review the molecular changes
      that are required for carcinogenesis and propose some criteria that, in the
      absence of epidemiological evidence, can be used to identify agents that cause or
      contribute to human cancer development. In the absence of epidemiological
      evidence, a given agent should be considered a human carcinogen when: (1) the
      agent causes or contributes to the development of tumors in animals that are of
      the same type as those tumors associated with exposure to the agent in humans;
      (2) the agent transforms or contributes to the transformation of human cells in
      culture and these cells are of the same type from which associated human
      malignancies arise; (3) there is molecular evidence that the agent interferes
      with one or more key molecular pathways in human cells which leads to the
      formation of human cancer.

PMID- 15489133
TI  - Current criteria to establish human carcinogens.
AB  - Several national and international health agencies worldwide have established
      carcinogen identification programs with the aim of identifying the agents and
      exposures that contribute to the global burden of cancer. These programs have
      many features in common. IARC's program is described in some detail, with an
      emphasis on how evaluations can be changed by mechanistic data. Recently, several
      programs have expanded on the guidance they provide in assessing mechanistic
      data. The most comprehensive example is EPA's recent draft final Guidelines for
      Carcinogen Risk Assessment. In all programs, however, the principal role of
      mechanistic information has been to support the positive results observed in
      epidemiological studies or to discount the relevance of positive results observed
      in experimental animal bioassays. An alternative paradigm for carcinogen
      identification is proposed, one where mechanistic studies have a central role,
      rather than a supporting one. Under this paradigm, potentially carcinogenic
      agents would be identified by (1) identifying the key precursor events and
      processes involved in human cancer and (2) testing to see whether an agent can
      affect these events and processes. Under this paradigm, which is consistent with
      a multi-factorial view of carcinogenesis, it might be possible to identify
      carcinogens through mechanistic understanding alone, without waiting for
      epidemiological studies or 2-year carcinogenesis bioassays in rats and mice. This
      paradigm asks the question, "What is a human carcinogen? Is it an agent that we
      observe to induce tumors, or more generally, an agent with a clear role in tumor
      development?"

PMID- 15489134
TI  - Role and limitations of epidemiology in establishing a causal association.
AB  - Cancer risk assessment is one of the most visible and controversial endeavors of
      epidemiology. Epidemiologic approaches are among the most influential of all
      disciplines that inform policy decisions to reduce cancer risk. The adoption of
      epidemiologic reasoning to define causal criteria beyond the realm of mechanistic
      concepts of cause-effect relationships in disease etiology has placed greater
      reliance on controlled observations of cancer risk as a function of putative
      exposures in populations. The advent of molecular epidemiology further expanded
      the field to allow more accurate exposure assessment, improved understanding of
      intermediate endpoints, and enhanced risk prediction by incorporating the
      knowledge on genetic susceptibility. We examine herein the role and limitations
      of epidemiology as a discipline concerned with the identification of carcinogens
      in the physical, chemical, and biological environment. We reviewed two examples
      of the application of epidemiologic approaches to aid in the discovery of the
      causative factors of two very important malignant diseases worldwide, stomach and
      cervical cancers. Both examples serve as paradigms of successful cooperation
      between epidemiologists and laboratory scientists in the pursuit of the
      understanding of cancer etiology.

PMID- 15489135
TI  - The epigenetics of cancer etiology.
AB  - Epigenetic dysregulation is central to cancer development and progression. This
      dysregulation includes hypomethylation leading to oncogene activation and
      chromosomal instability, hypermethylation and tumor suppressor gene silencing,
      and chromatin modification acting directly, and cooperatively with methylation
      changes, to modify gene expression. In addition, disrupted genomic imprinting
      appears to contribute to colorectal cancer risk, and serves as a gatekeeper in
      Wilms tumor. A cancer predisposing disorder, Beckwith-Wiedemann syndrome, usually
      arises from epigenetic errors, solidifying the causal role of epigenetics in
      cancer. While cancer epigenetics has been reviewed extensively elsewhere, the
      main focus of this review will be to present the view that epigenetics and
      genetics are complementary in the area of cancer etiology, the focus of this
      volume. I propose a hypothesis in which epigenetic alterations contribute to
      tumor progression, but they also increase the probability that genetic changes,
      when they occur, will lead to cancer initiation. This hypothesis could contribute
      to a new understanding of the role of environmental carcinogens that may not be
      fully explained through a purely genetic view or by tests, such as bacterial
      mutation frequency, that ignore epigenetic factors.

PMID- 15489136
TI  - Inflammation as a tumor promoter in cancer induction.
AB  - Opposing effects of inflammation on cancer have been described. Acute
      inflammation usually counteracts cancer development, while chronic inflammation
      promotes cancer development. Just as inactivation of the p53 pathway may be
      universal in the neoplasia, the activation of the NFkappaB pathway may,
      conversely, be frequent in carcinogenesis, and a requirement for inflammation and
      promotion. TNF, a key pro-inflammatory cytokine when binding to TNF receptor 1
      (TNFR1), may cause survival or apoptosis, dependent on biochemical modifications
      that determine the type of complex formed; one complex causes NFkappaB activation
      and gives a cell survival signal (pro-oncogenic), while the other (modified)
      complex recruits caspases and causes apoptosis (anti-oncogenic). Fas-ligand
      (FasL)-Fas interaction can also result in opposing effects on carcinogenesis due
      to similar mechanisms. While IL-6 counteracts apoptosis and can promote cancer
      development, interferons can increase DNA repair and stabilize p53, thereby be
      anti-oncogenic.

PMID- 15489137
TI  - Genetic alterations and DNA repair in human carcinogenesis.
AB  - A causal association between genetic alterations and cancer is supported by
      extensive experimental and epidemiological data. Mutational inactivation of tumor
      suppressor genes and activation of oncogenes are associated with the development
      of a wide range of cancers. The link between mutagenesis and carcinogenesis is
      particularly evident for cancers induced by chemical exposures, which, in some
      cases, lead to characteristic patterns of mutations. These "genotoxic," direct
      acting carcinogens form covalent adducts with DNA, which cause mutations during
      DNA replication. The link between mutagenesis and carcinogenesis is also
      supported by the observation that DNA repair defects are associated with an
      increased cancer risk. Normally, DNA repair mechanisms serve to suppress
      mutagenesis by correcting DNA damage before it can lead to heritable mutations.
      It has been postulated that mutagenesis plays a role in both the initiation phase
      and the progression phase of carcinogenesis, and that an essential step in the
      carcinogenic process is the development of a mutator state in which the normal
      cellular processes that suppress mutagenesis become compromised. Given the link
      between mutations and cancer, attempts have been made to use the mutational
      profile of cancer cells as an indicator of the causative agent. While this may be
      a valid approach in some cases, it is complicated by the role of endogenous
      processes in promoting mutagenesis. In addition, many important carcinogenic
      agents may enhance mutagenesis indirectly through suppression of DNA repair
      functions or stimulation of inappropriate cell proliferation. Epigenetic
      phenomena may also suppress gene expression without causing overt changes in DNA
      sequence.

PMID- 15489138
TI  - Modern criteria to determine the etiology of human carcinogens.
AB  - Rapid identification of human carcinogens before their dissemination into
      society, and exposure of worker and lay populations is an important goal of
      cancer research. Retroactively, verification of in-place human carcinogens is
      also required to target their removal, and other preventive and therapeutic
      strategies. The hierarchy of methods used historically for evaluation of
      carcinogenic potential is epidemiology > animal bioassays > mechanistic studies,
      and the focus has been on single agents that are genotoxic. However, mechanistic
      research has revealed several obligatory steps in carcinogenesis, tumor
      promotion, and progression that can now be used in screening studies with human
      cells in vitro and animal bioassays. These approaches should be combined with
      molecular epidemiology and molecular pathology to identify human carcinogens with
      more emphasis on evaluating combinations of suspect agents and mechanisms of
      action of epigenetic carcinogens.

PMID- 15489139
TI  - Infectious agents and cancer: criteria for a causal relation.
AB  - Infectious agents, mainly viruses, are among the few known causes of cancer and
      contribute to a variety of malignancies worldwide. The agents and cancers
      considered here are human papillomaviruses (cervical carcinoma); human
      polyomaviruses (mesotheliomas, brain tumors); Epstein-Barr virus (B-cell
      lymphoproliferative diseases and nasopharyngeal carcinoma); Kaposi's Sarcoma
      Herpesvirus (Kaposi's Sarcoma and primary effusion lymphomas); hepatitis B and
      hepatitis C viruses (hepatocellular carcinoma); Human T-cell Leukemia Virus-1 (T
      cell leukemias); and helicobacter pylori (gastric carcinoma), which account for
      up to 20% of malignancies around the globe. The criteria most often used in
      determining causality are consistency of the association, either epidemiologic or
      on the molecular level, and oncogenicity of the agent in animal models or cell
      cultures. However use of these generally applied criteria in deciding on
      causality is selective, and the criteria may be weighted differently. Whereas for
      most of the tumor viruses the viral genome persists in an integrated or episomal
      form with a subset of viral genes expressed in the tumor cells, some agents (HBV,
      HCV, helicobacter) are not inherently oncogenic, but infection leads to
      transformation of cells by indirect means. For some malignancies the viral agent
      appears to serve as a cofactor (Burkitt's lymphoma-EBV; mesothelioma - SV(40)).
      For others the association is inconsistent (Hodgkin's Disease, gastric
      carcinomas, breast cancer-EBV) and may either define subsets of these
      malignancies, or the virus may act to modify phenotype of an established tumor,
      contributing to tumor progression rather than causing the tumor. In these cases
      and for the human polyomaviruses the association with malignancy is less
      consistent or still emerging. In contrast despite the potent oncogenic properties
      of some strains of human adenovirus in tissue culture and animals the virus has
      not been linked with any human cancers. Finally it is likely that more agents,
      most likely viruses, both known and unidentified, have yet to be implicated in
      human cancer. In the meantime study of tumorigenic infectious agents will
      continue to illuminate molecular oncogenic processes.

PMID- 15489141
TI  - Head and Neck MR Imaging.

PMID- 15489142
TI  - Imaging of the upper cranial nerves I, III-VIII, and the cavernous sinuses.
AB  - This article discusses the upper cranial nerves (I, III-VIII) and their anatomy
      as it pertains to intra-axial nuclei and tracts, cisternal portions, and
      extracranial portions. In addition, the most common pathologic processes
      affecting the upper cranial nerves are discussed and illustrated. Because the
      evaluation of small structures requires imaging techniques that provide high
      resolution and contrast, MR imaging is the examination of choice. CT still plays
      a limited but important role in the evaluation of intraosseous portions of some
      cranial nerves.

PMID- 15489140
TI  - Environmental and chemical carcinogenesis.
AB  - People are continuously exposed exogenously to varying amounts of chemicals that
      have been shown to have carcinogenic or mutagenic properties in experimental
      systems. Exposure can occur exogenously when these agents are present in food,
      air or water, and also endogenously when they are products of metabolism or
      pathophysiologic states such as inflammation. It has been estimated that exposure
      to environmental chemical carcinogens may contribute significantly to the
      causation of a sizable fraction, perhaps a majority, of human cancers, when
      exposures are related to "life-style" factors such as diet, tobacco use, etc.
      This chapter summarizes several aspects of environmental chemical carcinogenesis
      that have been extensively studied and illustrates the power of mechanistic
      investigation combined with molecular epidemiologic approaches in establishing
      causative linkages between environmental exposures and increased cancer risks. A
      causative relationship between exposure to aflatoxin, a strongly carcinogenic
      mold-produced contaminant of dietary staples in Asia and Africa, and elevated
      risk for primary liver cancer has been demonstrated through the application of
      well-validated biomarkers in molecular epidemiology. These studies have also
      identified a striking synergistic interaction between aflatoxin and hepatitis B
      virus infection in elevating liver cancer risk. Use of tobacco products provides
      a clear example of cancer causation by a life-style factor involving carcinogen
      exposure. Tobacco carcinogens and their DNA adducts are central to cancer
      induction by tobacco products, and the contribution of specific tobacco
      carcinogens (e.g. PAH and NNK) to tobacco-induced lung cancer, can be evaluated
      by a weight of evidence approach. Factors considered include presence in tobacco
      products, carcinogenicity in laboratory animals, human uptake, metabolism and
      adduct formation, possible role in causing molecular changes in oncogenes or
      suppressor genes, and other relevant data. This approach can be applied to
      evaluation of other environmental carcinogens, and the evaluations would be
      markedly facilitated by prospective epidemiologic studies incorporating
      phenotypic carcinogen-specific biomarkers. Heterocyclic amines represent an
      important class of carcinogens in foods. They are mutagens and carcinogens at
      numerous organ sites in experimental animals, are produced when meats are heated
      above 180 degrees C for long periods. Four of these compounds can consistently be
      identified in well-done meat products from the North American diet, and although
      a causal linkage has not been established, a majority of epidemiology studies
      have linked consumption of well-done meat products to cancer of the colon, breast
      and stomach. Studies employing molecular biomarkers suggest that individuals may
      differ in their susceptibility to these carcinogens, and genetic polymorphisms
      may contribute to this variability. Heterocyclic amines, like most other chemical
      carcinogens, are not carcinogenic per se but must be metabolized by a family of
      cytochrome P450 enzymes to chemically reactive electrophiles prior to reacting
      with DNA to initiate a carcinogenic response. These same cytochrome P450 enzymes-
      as well as enzymes that act on the metabolic products of the cytochromes P450
      (e.g. glucuronyl transferase, glutathione S-transferase and others)--also
      metabolize chemicals by inactivation pathways, and the relative amounts of
      activation and detoxification will determine whether a chemical is carcinogenic.
      Because both genetic and environmental factors influence the levels of enzymes
      that metabolically activate and detoxify chemicals, they can also influence
      carcinogenic risk. Many of the phenotypes of cancer cells can be the result of
      mutations, i.e., changes in the nucleotide sequence of DNA that accumulate as
      tumors progress. These can arise as a result of DNA damage or by the
      incorporation of non-complementary nucleotides during DNA synthetic processes.
      Based upon the disparity between the infrequency of spontaneous mutations and the
      large numbers of mutations reported in human tumors, it has been postulated that
      cancers must exhibit a mutator phenotype, which would represent an early event in
      cancer progression. A mutator phenotype could be generated by mutations in genes
      that normally function to guarantee genetic stability. These mutations presumably
      arise via DNA damage by environmental or endogenous agents, but it remains to be
      determined whether the acquisition of a mutator phenotype is a necessary event
      during tumor progression.

PMID- 15489143
TI  - Imaging of the lower cranial nerves.
AB  - This article discusses the normal anatomy and pathologic entities that involve
      the lower cranial nerves. Normal anatomy is described and correlated with line
      diagrams and MR images. Distinct pathologic processes that involve the individual
      nerves along their various components are discussed. The imaging characteristics
      of these lesions are provided. Knowledge of the nuclear origins, the normal
      course of the cranial nerves, their func-tional components, and the imaging
      characteristics of pathologic lesions involving the nerves are important in any
      evaluation of cranial neuropathy.

PMID- 15489144
TI  - Laryngeal imaging.
AB  - Knowing the surgical options for treating laryngeal carcinomas and the factors
      that are used to select patients for radiation therapy leads to a more valuable
      and relevant interpretation of neck scans in patients with laryngeal tumors.
      Critical factors include tumor volume; cartilaginous invasion; spread across
      supraglottic-glottic-subglottic boundaries; infiltration of preepiglottic,
      paraglottic, and pharyngeal planes; and nodal disease. MR imaging offers greater
      sensitivity to cartilaginous invasion than CT but shows a higher rate of false
      positive studies. Direct coronal MR imaging is often valuable in assessing these
      issues.

PMID- 15489145
TI  - Imaging of neoplasms of the paranasal sinuses.
AB  - The assessment of sinonasal malignancies requires a multidisciplinary team
      approach.Advances in pretherapeutic imaging have significantly contributed to the
      managementof sinonasal tumors. CT and MR imaging play complementary roles in the
      assess-mentand staging of these malignancies by determining the presence or
      absence of exten-sionof disease into the skull base and its foramina, the orbit,
      and the intracranial compartment.

PMID- 15489146
TI  - Imaging of the hypopharynx and cervical esophagus.
AB  - Cross-sectional imaging with CT and MR imaging plays a crucial role in the
      evaluationof cancers of the hypopharynx and cervical esophagus. Clinical
      examination, includingendoscopy, often fails to detect the full extent of this
      tumor as it has high propensity togrow in submucosal fashion. Detailed
      description of the cross-sectional anatomy and ofthe tumor growth pattern will
      aid in the detection and evaluation of the full extent of thelesion. Post
      treatment imaging findings are addressed.

PMID- 15489147
TI  - MR imaging of perineural tumor spread.
AB  - Perineural tumor spread (PNS) is a common and potentially devastating
      complication of head and neck cancer. Because perineural tumor spread may be
      asymptomatic, the radi-ologist plays a critical role in the evaluation of the
      head and neck cancer patient. Although PNS may be seen on CT, MR imaging is far
      more sensitive and is the imaging modality of choice in the evaluation of
      perineural tumor spread.

PMID- 15489148
TI  - MR imaging of lymph nodes in the head and neck.
AB  - This article reviews imaging-based nodal classification, recent advancements in
      MR imaging techniques for lymph node imaging, and characteristics of MR imaging
      for necklymphadenopathy. Further technical development of MR imaging is necessary
      to improve accuracy of diagnosis of lymph node metastases in patients with no
      head and neck cancer. Development of new tissue-specific MR contrast agents and
      functional imaging studies to address biologic activity of lymph nodes is
      essential in the future.

PMID- 15489149
TI  - Imaging of the nasopharynx and skull base.
AB  - The prerequisite for the correct diagnosis and accurate delineation of skull base
      lesions is familiarity with the complex anatomy of the skull base. Imaging plays
      a central role in the management of skull base disease because this region is
      often difficult to evaluate clinically. CT and MR imaging are complementary; they
      are often used together to demonstrate the full disease extent. This article
      focuses on the critical anatomy of the skull base and how this knowledge
      contributes to accurate disease assessment.

PMID- 15489150
TI  - Imaging of the temporal bone.
AB  - Classical descriptions of the temporal bone are based on its five embryologically
      distinct osseous components: the petrous, tympanic, mastoid, squamous, and
      styloid portions.

PMID- 15489151
TI  - MR imaging of the temporomandibular joint.
AB  - Temporomandibular joint (TMJ) internal derangement is fairly prevalent in
      patients presenting with facial pain. MR imaging has become the primary modality
      for the assessment of the temporomandibular joint. A review of the normal anatomy
      and the key imaging findings of the different pathologic entities affecting this
      joint are presented. A reading algorithm to facilitate a systematic
      interpretation of the TMJ imaging study also is provided.

PMID- 15489152
TI  - MR imaging of salivary glands.
AB  - Diagnostic imaging of salivary glands has been revolutionized with the advent of
      cross-sectional imaging modalities like CT and MR imaging. In the era before CT,
      imaging of the salivary glands was relatively unrewarding and was used uncommonly
      by ear-nose-throat surgeons. Early diagnostic tests like plain films and
      sialography evaluated dilated parotid ducts and calculus disease within ducts or
      glands. Full evaluation of salivary glands, especially deep lobes of parotid
      gland and masses of minor salivary glands, was not possible by these methods,
      however. Imaging of the parotid glands has developed significantly since that
      time. CT and MR imaging greatly compliment physical and endoscopic examinations
      (and previous favorites like sialography) by direct visualization of previously
      blind areas of the salivary glands and extension of the disease process in
      surrounding tissue planes.

PMID- 15489153
TI  - MR imaging of the globe and optic nerve.
AB  - The superb contrast resolution of MR imaging has significantly improved
      radiologists' ability to evaluate the anterior visual pathways and globe. Optimal
      imaging of the orbit requires the radiologist to have a working understanding of
      the clinical questions the ophthalmologist needs answered. In this article, basic
      orbit anatomy, MR imaging protocols for the orbit, and common clinical scenarios
      encountered when imaging the orbit are reviewed, with a focus on the optic nerve
      and globe.

PMID- 15489154
TI  - New imaging techniques: integrating structural and functional imaging in the head
      and neck.
AB  - Traditionally, the mainstay of head and neck MR imaging has been the
      identification of structural alterations resulting from pathology. Now, the
      advent of fast MR imaging techniques provides the opportunity for radiologists to
      integrate structural and functional imaging in the head and neck. This article
      highlights functional imaging techniques that provide a means toward a complete
      evaluation of structural integrity and function in various systems of the head
      and neck.

PMID- 15489155
TI  - MR-guided ablation of head and neck tumors.
AB  - Interstitial laser-induced thermotherapy (LITT) is a minimally invasive technique
      for lo-caltumor destruction within solid organs using optical fibers to deliver a
      high-energylaser to the target lesion. MR imaging is used both for placement of
      the laser in the tumorand for monitoring progress of thermocoagulation caused by
      the laser. The success ofLITT is dependent on the delivery of the optical fibers
      to the target area, real-time mon-itoringof the effects of the treatment, and
      subsequent evaluation of the extent of thermaldamage. The key to achieving these
      objectives is the imaging methods used. The thermo-sensitivityof certain MR
      sequences is the key to real-time monitoring, allowing accurateestimation of the
      extent of thermal damage.

PMID- 15489156
TI  - The genetics of autism.

PMID- 15489157
TI  - An 'inside-the-box' approach to drug resistance.
AB  - Drug resistance is a growing problem in medicine that demands creative solutions.
      In this issue, Schiffer and colleagues describe their novel approach to
      pinpointing hot spots of resistance, which might lead to new anti-HIV
      therapeutics.

PMID- 15489158
TI  - Catching proteases in action with microarrays.
AB  - Proteases regulate many essential functions in biology, yet their precise roles
      are only beginning to be unraveled. In this issue, two related papers describe a
      novel method to dissect specific protease activities from complex mixtures.

PMID- 15489159
TI  - A suppression strategy for antibiotic discovery.
AB  - High-throughput phenotype screening and target identification have been combined
      in an effort to isolate antimicrobial, small-molecule therapeutics. This
      approach, developed by Brown and colleagues and reported in this issue, is a
      major technological advance for antimicrobial drug discovery.

PMID- 15489160
TI  - Combating susceptibility to drug resistance: lessons from HIV-1 protease.
AB  - Drug resistance is a major obstacle in modern medicine. However, resistance is
      rarely considered in drug development and may inadvertently be facilitated, as
      many designed inhibitors contact residues that can mutate to confer resistance,
      without significantly impairing function. Contemporary drug design often ignores
      the detailed atomic basis for function and primarily focuses on disrupting the
      target's activity, which is necessary but not sufficient for developing a robust
      drug. In this study, we examine the impact of drug-resistant mutations in HIV-1
      protease on substrate recognition and demonstrate that most primary active site
      mutations do not extensively contact substrates, but are critical to inhibitor
      binding. We propose a general, structure-based strategy to reduce the probability
      of drug resistance by designing inhibitors that interact only with those residues
      that are essential for function.

PMID- 15489161
TI  - Molecular dynamics simulation links conformation of a pore-flanking region to
      hyperekplexia-related dysfunction of the inhibitory glycine receptor.
AB  - Inhibitory glycine receptors mediate rapid synaptic inhibition in mammalian
      spinal cord and brainstem. The previously identified hyperekplexia mutation
      GLRA1(P250T), located within the intracellular TM1-2 loop of the GlyR alpha1
      subunit, results in altered receptor activation and desensitization. Here,
      elementary steps of ion channel function of alpha1(250) mutants were resolved and
      shown to correlate with hydropathy and molar volume of residue alpha1(250).
      Single-channel recordings and rapid activation kinetic studies using laser pulse
      photolysis showed reduced conductance but similar open probability of
      alpha1(P250T) mutant channels. Molecular dynamics simulation of a helix-turn
      helix motif representing the intracellular TM1-2 domain revealed alterations in
      backbone conformation, indicating an increased flexibility in these mutants that
      paralleled changes in elementary steps of channel function. Thus, the
      architecture of the TM1-2 loop is a critical determinant of ion channel
      conductance and receptor desensitization.

PMID- 15489162
TI  - PNA-encoded protease substrate microarrays.
AB  - Our current understanding of the role and regulation of protease activity in
      normal and pathogenic processes is limited by our ability to measure and
      deconvolute their enzymatic activity. To address this limitation, an approach was
      developed that utilizes rhodamine-based fluorogenic substrates encoded with PNA
      tags. The PNA tags address each of the substrates to a predefined location on an
      oligonucleotide microarray through hybridization, thus allowing the deconvolution
      of multiple signals from a solution. A library of 192 protease substrates was
      prepared by split and mix combinatorial synthesis. The methodology and validation
      of this approach for profiling proteolytic activity from single proteases and
      from those in crude cell lysates as well as clinical blood samples is described.

PMID- 15489163
TI  - Activity profile of dust mite allergen extract using substrate libraries and
      functional proteomic microarrays.
AB  - Enzymatic activity in the fecal droppings from the house dust mite has been
      postulated to contribute to the elicited allergic response. Screening dust mite
      extracts through 137,180 tetrapeptide fluorogenic substrates allowed for the
      characterization of proteolytic substrate specificity from the potential cysteine
      and serine proteases in the extract. The extract was further screened against a
      4000 member peptide nucleic acid (PNA) encoded inhibitor library designed to
      target cysteine proteases using microarray detection. Affinity chromatography
      coupled with mass spectrometry identified Der p 1 as one of the proteases
      targeted by the PNA inhibitors in the dust mite lysate. A phenotypic readout of
      Der p 1 function in allergy progression was demonstrated by the inhibition of
      CD25 cleavage from T cells by dust mite extract that had been treated with the
      Der p 1 inhibitor identified from the PNA-encoded inhibitor library.

PMID- 15489164
TI  - The biosynthesis of the thiazole phosphate moiety of thiamin: the sulfur transfer
      mediated by the sulfur carrier protein ThiS.
AB  - Thiamin-pyrophosphate is an essential cofactor in all living systems. The
      biosynthesis of both the thiazole and the pyrimidine moieties of this cofactor
      involves new biosynthetic chemistry. Thiazole-phosphate synthase (ThiG) catalyses
      the formation of the thiazole moiety of thiamin-pyrophosphate from 1-deoxy-D
      xylulose-5-phosphate (DXP), dehydroglycine and the sulfur carrier protein (ThiS),
      modified on its carboxy terminus as a thiocarboxylate (ThiS-thiocarboxylate).
      Thiazole biosynthesis is initiated by the formation of a ThiG/DXP imine, which
      then tautomerizes to an amino-ketone. In this paper we study the sulfur transfer
      from ThiS-thiocarboxylate to this amino-ketone and trap a new thioenolate
      intermediate. Surprisingly, thiazole formation results in the replacement of the
      ThiS-thiocarboxylate sulfur with an oxygen from DXP and not from the buffer, as
      shown by electrospray ionization Fourier transform mass spectrometry (ESI-FTMS)
      using (18)O labeling of the 13C-, 15N-depleted protein. These observations
      further clarify the mechanism of the complex thiazole biosynthesis in bacteria.

PMID- 15489165
TI  - Crystal structure and mechanistic implications of 1-aminocyclopropane-1
      carboxylic acid oxidase--the ethylene-forming enzyme.
AB  - The final step in the biosynthesis of the plant signaling molecule ethylene is
      catalyzed by 1-aminocyclopropane-1-carboxylic acid oxidase (ACCO). ACCO requires
      bicarbonate as an activator and catalyzes the oxidation of ACC to give ethylene,
      CO2, and HCN. We report crystal structures of ACCO in apo-form (2.1 A resolution)
      and complexed with Fe(II) (2.55 A) or Co(II) (2.4 A). The active site contains a
      single Fe(II) ligated by three residues (His177, Asp179, and His234), and it is
      relatively open compared to those of the 2-oxoglutarate oxygenases. The side
      chains of Arg175 and Arg244, proposed to be involved in binding bicarbonate,
      project away from the active site, but conformational changes may allow either or
      both to enter the active site. The structures will form a basis for future
      mechanistic and inhibition studies.

PMID- 15489166
TI  - A polymorphic pocket at the P10 position contributes to peptide binding
      specificity in class II MHC proteins.
AB  - Peptides bind to class II major histocompatibility complex (MHC) proteins in an
      extended conformation. Pockets in the peptide binding site spaced to accommodate
      peptide side chains at the P1, P4, P6, and P9 positions have been previously
      characterized and help to explain the obtained peptide binding specificity.
      However, two peptides differing only at P10 have significantly different binding
      affinities for HLA-DR1. The structure of HLA-DR1 in complex with the tighter
      binding peptide shows that the peptide binds in the usual polyproline type II
      conformation, but with the P10 residue accommodated in a shallow pocket at the
      end of the binding groove. HLA-DR1 variants with polymorphic residues at these
      positions were produced and found to exhibit different side chain specificity at
      the P10 position. These results define a new specificity position in HLA-DR
      proteins.

PMID- 15489167
TI  - Novel avilamycin derivatives with improved polarity generated by targeted gene
      disruption.
AB  - The oligosaccharide antibiotics avilamycin A and C are produced by Streptomyces
      viridochromogenes Tu57. Both consist of a heptasaccharide chain, which is
      attached to a polyketide-derived dichloroisoeverninic acid moiety. They show
      excellent antibiotic activity against Gram-positive bacteria. Both molecules are
      modified by O-methylation at different positions, which contributes to poor water
      solubility and difficulties in galenical drug development. In order to generate
      novel avilamycin derivatives with improved polarity and improved pharmacokinetic
      properties, we generated a series of mutants with one, two, or three mutated
      methyltransferase genes. Based on the structure of the novel avilamycin
      derivatives, the exact function of three methyltransferases, AviG2, AviG5, and
      AviG6, involved in avilamycin biosynthesis could be assigned.

PMID- 15489168
TI  - Disruption of protein-membrane binding and identification of small-molecule
      inhibitors of coagulation factor VIII.
AB  - Factor VIII is a critical member of the blood coagulation cascade. It binds to
      the membrane surfaces of activated platelets at the site of vascular injury via a
      highly specific interaction between factor VIII's carboxy-terminal C2 domain and
      their phosphatidylserine-rich lipid bilayer. We have identified small-molecule
      inhibitors of factor VIII's membrane binding activity that have IC50 values as
      low as 2.5 microM. This interaction is approximately 10(3)-fold tighter than that
      of free o-phospho-L-serine. These compounds also inhibit factor VIII-dependent
      activation of factor X, indicating that disruption of membrane lipid binding
      leads to inhibition of the intrinsic coagulation pathway. The tightest binding
      inhibitor is specific and does not prevent membrane binding by the closely
      related coagulation factor V. These results indicate that this and related
      compounds may be used as leads to develop novel antithrombotic agents.

PMID- 15489169
TI  - Multicopy suppressors for novel antibacterial compounds reveal targets and drug
      efflux susceptibility.
AB  - Gene dosage has frequently been exploited to select for genetic interactions
      between a particular mutant and clones from a random genomic library at high
      copy. We report here the first use of multicopy suppression as a forward genetic
      method to determine cellular targets and potential resistance mechanisms for
      novel antibacterial compounds identified through high-throughput screening. A
      screen of 8640 small molecules for growth inhibition of a hyperpermeable strain
      of Escherichia coli led to the identification of 49 leads for suppressor
      selection from clones harboring an E. coli genomic library. The majority of
      suppressors were found to encode the multidrug efflux pump AcrB, indicating that
      those compounds were substrates for efflux. Two leads, which produced clones
      containing the gene folA, encoding dihydrofolate reductase (DHFR), proved to
      target DHFR in vivo and were competitive inhibitors in vitro.

PMID- 15489170
TI  - Wide-angle X-ray solution scattering as a probe of ligand-induced conformational
      changes in proteins.
AB  - A chemical genetics approach to functional analysis of gene products utilizes
      high-throughput target-based screens of compound libraries to identify ligands
      that modulate the activity of proteins of interest. Candidates are further
      screened using functional assays designed specifically for the protein--and
      function--of interest, suffering from the need to customize the assay to each
      protein. An alternative strategy is to utilize a probe to detect the structural
      changes that usually accompany binding of a functional ligand. Wide-angle X-ray
      scattering from proteins provides a means to identify a broad range of ligand
      induced changes in secondary, tertiary, and quaternary structure. The speed and
      accuracy of data acquisition, combined with the label-free targets and binding
      conditions achievable, indicate that WAXS is well suited as a moderate-throughput
      assay in the detection and analysis of protein-ligand interactions.

PMID- 15489171
TI  - High-throughput screening identifies inhibitors of the SARS coronavirus main
      proteinase.
AB  - The causative agent of severe acute respiratory syndrome (SARS) has been
      identified as a novel coronavirus, SARS-CoV. The main proteinase of SARS-CoV,
      3CLpro, is an attractive target for therapeutics against SARS owing to its
      fundamental role in viral replication. We sought to identify novel inhibitors of
      3CLpro to advance the development of appropriate therapies in the treatment of
      SARS. 3CLpro was cloned, expressed, and purified from the Tor2 isolate. A
      quenched fluorescence resonance energy transfer assay was developed for 3CLpro to
      screen the proteinase against 50,000 drug-like small molecules on a fully
      automated system. The primary screen identified 572 hits; through a series of
      virtual and experimental filters, this number was reduced to five novel small
      molecules that show potent inhibitory activity (IC50 = 0.5-7 microM) toward SARS
      CoV 3CLpro.

PMID- 15489173
TI  - Production of hybrid 16-membered macrolides by expressing combinations of
      polyketide synthase genes in engineered Streptomyces fradiae hosts.
AB  - Combinations of the five polyketide synthase (PKS) genes for biosynthesis of
      tylosin in Streptomyces fradiae (tylG), spiramycin in Streptomyces ambofaciens
      (srmG), or chalcomycin in Streptomyces bikiniensis (chmG) were expressed in
      engineered hosts derived from a tylosin-producing strain of S. fradiae.
      Surprisingly efficient synthesis of compounds predicted from the expressed hybrid
      PKS was obtained. The post-PKS tailoring enzymes of tylosin biosynthesis acted
      efficiently on the hybrid intermediates with the exception of TylH-catalyzed
      hydroxylation of the methyl group at C14, which was efficient if C4 bore a methyl
      group, but inefficient if a methoxyl was present. Moreover, for some compounds,
      oxidation of the C6 ethyl side chain to an unprecedented carboxylic acid was
      observed. By also expressing chmH, a homolog of tylH from the chalcomycin gene
      cluster, efficient hydroxylation of the 14-methyl group was restored.

PMID- 15489172
TI  - A new curcumin derivative, HBC, interferes with the cell cycle progression of
      colon cancer cells via antagonization of the Ca2+/calmodulin function.
AB  - HBC (4-[3,5-Bis-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-4,5-dihydro-pyrazol-1-yl]
      benzoic acid) is a recently developed curcumin derivative which exhibits potent
      inhibitory activities against the proliferation of several tumor cell lines. In
      the present study, we identified Ca2+/calmodulin (Ca2+/CaM) as a direct target
      protein of HBC using phage display biopanning. Ca2+/CaM-expressing phages
      specifically bound to the immobilized HBC, and the binding was Ca2+ dependent.
      Moreover, flexible docking modeling demonstrated that HBC is compatible with the
      binding cavity for a known inhibitor, W7, in the C-terminal hydrophobic pocket of
      Ca2+/CaM. In biological systems, HBC induced prolonged phosphorylation of ERK1/2
      and activated p21(WAF1) expression, resulting in the induction of G0/G1 cell
      cycle arrest in HCT15 colon cancer cells. These results suggest that HBC inhibits
      the cell cycle progression of colon cancer cells via antagonizing of Ca2+/CaM
      functions.

PMID- 15489176
TI  - Obstetric and gynecologic malpractice in Turkey: incidence, impact, causes and
      prevention.
AB  - The Forensic Medicine Association was established in Turkey by law number 2659
      for the purpose of providing expertise in legal cases. In this study the opinions
      given by the lawcourts and public defenders in the Forensic Medicine
      Association's First, Second, Third, and Fifth Specialization Divisions between
      the years 1990 and 2000 (approximately 680,000 files) were examined
      retrospectively. It was determined from these that there were 636 cases of
      medical malpractice. In examining the distribution of cases based on specialty
      branch, it was established that 16.82% (n=107) were in the area of obstetrics and
      gynecology, 10.69% (n=68) in general surgery, 10.53% in neurology and
      neurosurgery, and the remaining areas were found to be at lower percentages. It
      also showed that in recent years there has been an increase in the number of
      cases claiming medical malpractice in the area of obstetrics and gynecology, and
      that 58% of the cases (n=62) from 1998 to 2000 were in this area. 96% of the 107
      cases that claimed malpractice in the area of obstetrics and gynecology were
      found to be related to obstetrics and 3.8% (n=4) to gynecology and surgical
      procedures. In 31% (n=33) of the 107 cases fault was found; all of the cases
      where medical malpractice was found were in the area of obstetrics and none of
      the cases related to gynecology were found to have an element of error. Cases
      that had an element of error were evaluated from the aspect of profession of the
      health care personnel at fault, areas of fault, places where fault occurred,
      situations that resulted in death, cause of death, whether or not an autopsy was
      done, injury that resulted from fault, intervention that was done, and obstetric
      and gynecologic risk factors that set the stage for claims. Care standards and
      breach of standards were examined.

PMID- 15489177
TI  - Child abuse in Chandigarh, India, and its implications.
AB  - Few abuses of human rights are so universally condemned but at the same time so
      universally practiced as child abuse. Over the centuries, children have been
      subjected to physical, sexual and emotional abuse as well as neglect. By any
      objective measures, this issue should rank high on the global agenda but in
      practice it is surrounded by a wall of silence and perpetuated by ignorance.
      Child sexual abuse is a dark reality that routinely inflicts our daily lives but
      in a majority of cases it goes unnoticed and unreported on account of the
      innocence of the victim, stigma attached to the act, callousness and
      insensitivity of the investigating and the law enforcement agencies, etc. A child
      who has been sexually abused is traumatized for life but it is only much later in
      life when the emotional and psychological trauma aggravates that such people seek
      medical help. There is an urgent need to take up the problem as a larger social
      issue where the society has a responsibility to help the victims overcome their
      trauma and move on with life as normally as possible. We report a retrospective
      review of children (age<16 years) referred for medicolegal examination, an
      autopsy in Chandigarh, India, between 2000 and 2003.

PMID- 15489178
TI  - The perception of yellow in bruises.
AB  - For forensic purposes, the presence of the colour yellow in a bruise may be
      regarded as indicating it is not recent. However, a previous study has shown that
      observers may disagree in their description of the colours in a bruise. This
      study was designed to determine how consistent observers are in perceiving the
      presence of yellow. Subjects were shown a series of photographs of a bruise that
      had been digitally modified (Adobe Photoshop) to contain amounts of yellow that
      increased from 2% to 20%. The point at which subjects first perceived the colour
      yellow was recorded. The perception threshold for yellow ranged from 4% to 16%
      (mean=8.7%, median=8%) in the 50 subjects that had normal colour vision.
      Statistical analysis indicated that an individual's yellow perception threshold
      increased by 0.07% each year, but gender had no effect. The results reveal that
      there is variability in the perception threshold for yellow in the general
      population and that a subject's ability to perceive yellow in a bruise declines
      with age.

PMID- 15489179
TI  - Fitness to be interviewed.

PMID- 15489180
TI  - Effect of combined exposure to carbon monoxide and cyanides in selected forensic
      cases.
AB  - Carbon monoxide is a toxic gas with potentially lethal action, which forms as a
      result of incomplete combustion in conditions where there is a lack of oxygen and
      which, therefore, is present in varying percentages in environments where fire
      develops. In addition to carbon monoxide, other factors such as cyanide may
      contribute or might actually be the primary cause of a subject's demise. In cases
      of exposure to both substances, the role of cyanide as a toxic/lethal agent in
      death by asphyxiation is still not clear: some authors attribute a primary action
      to such a gas in causing the demise, others consider carbon monoxide to be the
      only cause of the lethal event. For this reason it is in the interest of forensic
      medicine to study all lethal cases of exposure to toxic substances originating
      from fires of various types of materials, in order to determine information
      regarding kinetic action and the possible strengthening of the effect of the two
      substances. Two case studies are presented here, in which the results of the
      toxicological examinations are quite different, and the contributions of CO and
      HCN in a fire asphyxiation are considered.

PMID- 15489181
TI  - Unexpected sudden death due to a spontaneous rupture of a gastric dissecting
      aneurysm: an autopsy case suggesting the importance of the double-rupture
      phenomenon.
AB  - Gastric dissecting aneurysm is a very rare lesion with a potential risk of fatal
      rupture. Differentiating this from a traumatic lesion may be important in
      forensic casework. We report an autopsy case of sudden death due to a clinically
      overlooked spontaneous rupture of gastric dissecting aneurysm. A 91-year-old
      Japanese male visited a hospital with complaints of back pain and general
      fatigue, and then died at his home about 4 h later. Postmortem examination
      revealed massive hemoperitoneum and a subserosal hematoma originating from a
      vascular lesion at the lesser gastric curvature with a serosal tear. The
      histological findings were compatible with segmental arterial mediolysis (SAM).
      The pathological findings and clinical course suggested the possible 'double
      rupture phenomenon' (delayed fatal rupture). This case suggested the importance
      of careful investigation such a vascular lesion in medico-legal practice, not
      only to differentiate from traumatic injury but also to investigate the process
      of dying.

PMID- 15489182
TI  - Policing pregnancy: Tregs help keep the peace.

PMID- 15489183
TI  - Looking through ion channels: recharged concepts in T-cell signaling.

PMID- 15489184
TI  - Let's go mucosal: communication on slippery ground.

PMID- 15489185
TI  - The immunology of gluten sensitivity: beyond the gut.

PMID- 15489186
TI  - Multichain immune recognition receptor signaling: different players, same game?

PMID- 15489187
TI  - The composition of intrahepatic lymphocytes: shaped by selective recruitment?
AB  - Intrahepatic lymphocytes have a distinct subset composition and phenotype.
      Compared with lymphoid tissues, the frequency of natural killer (NK) cells, NKT
      cells and gammadelta T cells among total lymphocytes is increased within the
      liver, and alphabeta T cells are predominantly effector/memory cells. Divergent
      hypotheses on the origin of intrahepatic T cells have emerged to explain this; in
      these hypotheses, either local development or selective recruitment of cells into
      the liver dominates. This Opinion highlights findings showing that the migratory
      preferences of lymphocyte subsets reflect their representation within the liver
      surprisingly well, suggesting that the composition of intrahepatic lymphocytes,
      in the absence of inflammation, is largely shaped by the dynamics of cell entry
      and exit into and from the liver.

PMID- 15489188
TI  - Different roles for glucocorticoids in thymocyte homeostasis?
AB  - Glucocorticoids (GCs) have important immunoregulatory effects on thymocytes and T
      cells. Ectopic production of GCs has been demonstrated in thymic epithelial cells
      (TECs) but the role of GCs in thymocyte homeostasis is controversial. Studies in
      several different mouse models, genetically modified for the GC receptor (GR)
      expression or function, have demonstrated conflicting results in terms of the
      effect of the hormone on thymocytes. Here, we summarize these data and suggest
      that GCs can mediate both positive and negative effects in the organ depending on
      the local hormonal concentration. Basal GC levels might promote growth of early
      thymocytes in young mice, and increased levels, generated through a stress
      reaction, apoptosis in these cells. A gradual loss of GC synthesis in TECs during
      aging might contribute to thymic involution, a process so far unexplained.

PMID- 15489189
TI  - IFN-inducible GTPases and immunity to intracellular pathogens.
AB  - By eliciting host antimicrobial programs in nearly all nucleated cells
      interferons (IFNs) help orchestrate the innate immune response of mammals to a
      diverse array of microbial pathogens. Recent work has highlighted the complexity
      of this transcriptional repertoire and the emergence of several families of IFN
      inducible guanosine 5' triphosphatases (GTPases)--p47, guanylate-binding protein
      (GBP), Mx and very large inducible GTPases (VLIG)--that subsume pathogen-specific
      roles. Such specificity arises from a combination of both the type and timing of
      inductive stimuli, target-cell population, subcellular binding partners and the
      infectious agent encountered. Evolution of different GTPase families to combat
      compartmentalized versus cytosolic pathogens reveals a hitherto unexpected level
      of intracellular discrimination during vertebrate host defense.

PMID- 15489190
TI  - T-lymphocyte death during shutdown of an immune response.
AB  - The immune system serves to protect organisms from infectious pathogens. During
      infection, lymphocytes and cells of the innate immune system, expressing
      receptors that recognize foreign antigens, proliferate and differentiate to
      develop effector functions that help to kill the pathogens. Effector functions,
      such as cellular or antibody mediated cytotoxicity, and inflammatory cytokines
      can be harmful to the host. To limit damage to healthy tissue, mechanisms have
      evolved to shut down immune responses, including cell inactivation and cell
      death. Here we discuss recent studies demonstrating that the death of antigen
      activated T lymphocytes during termination of an immune response is initiated by
      the BH3-only Bcl-2 family member Bim and also requires its multi-BH domain pro
      apoptotic relatives Bax and Bak.

PMID- 15489191
TI  - Thematic Issue "Apoptosis-like cell death programs in yeasts".

PMID- 15489192
TI  - Multiple cell death programs: Charon's lifts to Hades.
AB  - Cells use different pathways for active self-destruction as reflected by
      different morphology: while in apoptosis (or "type I") nuclear fragmentation
      associated with cytoplasmic condensation but preservation of organelles is
      predominant, autophagic degradation of cytoplasmic structures preceding nuclear
      collapse is a characteristic of a second type of programmed cell death (PCD). The
      diverse morphologies can be attributed--at least to some extent--to distinct
      biochemical and molecular events (e.g. caspase-dependent and -independent death
      programs; DAP-kinase activity, Ras-expression). However, apoptosis and autophagic
      PCD are not mutually exclusive phenomena. Rather, diverse PCD programs emerged
      during evolution, the conservation of which apparently allows cells a flexible
      response to environmental changes, either physiological or pathological.

PMID- 15489193
TI  - Programmed cell death in fission yeast.
AB  - Recently a metacaspase, encoded by YCA1, has been implicated in a primitive form
      of apoptosis or programmed cell death in yeast. Previously it had been shown that
      over-expression of mammalian pro-apoptotic proteins can induce cell death in
      yeast, but the mechanism of how cell death occurred was not clearly established.
      More recently, it has been shown that DNA or oxidative damage, or other cell
      cycle blocks, can result in cell death that mimics apoptosis in higher cells.
      Also, in fission yeast deletion of genes required for triacylglycerol synthesis
      leads to cell death and expression of apoptotic markers. A metacaspase sharing
      greater than 40% identity to budding yeast Yca1 has been identified in fission
      yeast, however, its role in programmed cell death is not yet known. Analysis of
      the genetic pathways that influence cell death in yeast may provide insights into
      the mechanisms of apoptosis in all eukaryotic organisms.

PMID- 15489194
TI  - Yeast replicative life span--the mitochondrial connection.
AB  - Mitochondria have been associated with aging in many experimental systems through
      the damaging action of reactive oxygen species. There is more, however, to the
      connection between mitochondria and Saccharomyces cerevisiae longevity and aging.
      Induction of the retrograde response, a pathway signaling mitochondrial
      dysfunction, results in the extension of life span and postponement of the
      manifestations of aging, changing the metabolic and stress resistance status of
      the cell. A paradox associated with the retrograde response is the simultaneous
      triggering of extrachromosomal ribosomal DNA circle (ERC) production, because of
      the deleterious effect these circles have on yeast longevity. The retrograde
      response gene RTG2 appears to play a pivotal role in ERC production, linking
      metabolism and genome stability. In addition to mother cell aging, mitochondria
      are important in establishment of age asymmetry between mother and daughter
      cells. The results more generally point to the existence of a mechanism to
      "filter" damaged components from daughter cells, a form of checkpoint control.
      Mitochondrial integrity is affected by the PHB1 and PHB2 genes, which encode
      inner mitochondrial membrane chaperones called prohibitins. The Phb1/2 proteins
      protect the cell from imbalances in the production of mitochondrial proteins.
      Such imbalances appear to cause a stochastic stratification of the yeast
      population with the appearance of short-lived cells. Ras2p impacts this process.
      Maintenance of mitochondrial membrane potential and the provision of Krebs cycle
      intermediates for biosyntheses appear to be crucial elements in yeast longevity.
      In sum, it is clear that mitochondria lie at the nexus of yeast longevity and
      aging.

PMID- 15489195
TI  - Mitochondria damage checkpoint in apoptosis and genome stability.
AB  - Mitochondria perform multiple cellular functions including energy production,
      cell proliferation and apoptosis. Studies described in this paper suggest a role
      for mitochondria in maintaining genomic stability. Genomic stability appears to
      be dependent on mitochondrial functions involved in maintenance of proper
      intracellular redox status, ATP-dependent transcription, DNA replication, DNA
      repair and DNA recombination. To further elucidate the role of mitochondria in
      genomic stability, I propose a mitochondria damage checkpoint (mitocheckpoint)
      that monitors and responds to damaged mitochondria. Mitocheckpoint can coordinate
      and maintain proper balance between apoptotic and anti-apoptotic signals. When
      mitochondria are damaged, mitocheckpoint can be activated to help cells repair
      damaged mitochondria, to restore normal mitochondrial function and avoid
      production of mitochondria-defective cells. If mitochondria are severely damaged,
      mitocheckpoint may not be able to repair the damage and protect cells. Such an
      event triggers apoptosis. If damage to mitochondria is continuous or persistent
      such as damage to mitochondrial DNA resulting in mutations, mitocheckpoint may
      fail which can lead to genomic instability and increased cell survival in yeast.
      In human it can cause cancer. In support of this proposal we provide evidence
      that mitochondrial genetic defects in both yeast and mammalian systems lead to
      impaired DNA repair, increased genomic instability and increased cell survival.
      This study reveals molecular genetic mechanisms underlying a role for
      mitochondria in carcinogenesis in humans.

PMID- 15489196
TI  - Uth1p: a yeast mitochondrial protein at the crossroads of stress, degradation and
      cell death.
AB  - UTH1 is a yeast aging gene that has been identified on the basis of stress
      resistance and longer life span of mutants. It was also shown to participate in
      mitochondrial biogenesis. The absence of Uth1p was found to trigger resistance to
      autophagy induced by rapamycin. Uth1p is therefore the first mitochondrial
      protein proven to be required for the autophagic degradation of mitochondria.
      Since this protein is also involved in yeast cell death induced by heterologous
      expression of the pro-apoptotic protein Bax, the results are discussed in the
      light of evidence suggesting a co-regulation of apoptosis and autophagy in
      mammalian cells.

PMID- 15489197
TI  - Involvement of the yeast metacaspase Yca1 in ubp10Delta-programmed cell death.
AB  - UBP10 encodes a deubiquitinating enzyme of Saccharomyces cerevisiae. Its
      inactivation results in a complex phenotype characterized by a subpopulation of
      cells that exhibits the typical cellular markers of apoptosis. Here, we show that
      additional deletion of YCA1, coding for the yeast metacaspase, suppressed the
      ubp10 disruptant phenotype. Moreover, YCA1 overexpression, without any external
      stimulus, had a detrimental effect on growth and viability of ubp10 cells
      accompanied by an increase of apoptotic cells. This response was completely
      abrogated by ascorbic acid addition. We also observed that cells lacking UBP10
      had an endogenous caspase activity, revealed by incubation in vivo with FITC
      labeled VAD-fmk. All these results argue in favour of an involvement of the yeast
      metacaspase in the active cell death triggered by loss of UBP10 function.

PMID- 15489198
TI  - Production of reactive oxygen species and loss of viability in yeast
      mitochondrial mutants: protective effect of Bcl-xL.
AB  - The capacity of yeast cells to produce reactive oxygen species (ROS), both as a
      response to manipulation of mitochondrial functions and to growth conditions, was
      estimated and compared with the viability of the cells. The chronological ageing
      of yeast cells (growth to late-stationary phase) was accompanied by increased ROS
      accumulation and a significantly higher loss of viability in the mutants with
      impaired mitochondrial functions than in the parental strain. Under these
      conditions, the ectopic expression of mammalian Bcl-x(L), which is an anti
      apoptotic protein, allowed cells to survive longer in stationary phase. The
      protective effect of Bcl-x(L) was more prominent in respiratory-competent cells
      that contained defects in mitochondrial ADP/ATP translocation, suggesting a model
      for Bcl-x(L) regulation of chronological ageing at the mitochondria. Yeast can
      also be triggered into apoptosis-like cell death, at conditions leading to the
      depletion of the intramitochondrial ATP pool, as a consequence of the parallel
      inhibition of mitochondrial respiration and ADP/ATP translocation. If respiratory
      deficient (rho(0)) cells were used, no correlation between the numbers of ROS
      producing cells and the viability loss in the population was observed, indicating
      that ROS production may be an accompanying event. The protective effect of Bcl
      x(L) against death of these cells suggests a mitochondrial mechanism which is
      different from the antioxidant activity of Bcl-x(L).

PMID- 15489199
TI  - The role of respiration, reactive oxygen species and oxidative stress in mother
      cell-specific ageing of yeast strains defective in the RAS signalling pathway.
AB  - We show that the dominant activated allele of the yeast RAS gene,
      RAS2(ala18,val19), led to redox imbalance in exponential-phase cells and to
      excretion of almost all of the cellular glutathione into the medium when the
      cells reached early-stationary phase. The mitochondria of the mutant stained
      strongly with dihydrorhodamine 123 (DHR) and the cells displayed a very short
      mother cell-specific lifespan. Adding 1 mM reduced glutathione (GSH) to the
      medium partly restored the lifespan. The corresponding RAS2(+) rho-zero strain
      also displayed a short lifespan, excreted nearly all of its GSH, and stained
      positively with DHR. Adding 1 mM GSH completely restored the lifespan of the
      RAS2(+) rho-zero strain to that of the wild-type cells. The double mutant
      RAS2(ala18,val19) rho-zero cells showed the same lifespan as the
      RAS2(ala18,val19) cells, and the effect of glutathione in restoring the lifespan
      was the same, indicating that both mutations shorten lifespan through a similar
      mechanism. In the RAS2(ala18,val19) mutant strain and its rho-zero derivative we
      observed for the first time a strong electron spin resonance (ESR) signal
      characteristic of the superoxide radical anion. The mutant cells were, therefore,
      producing superoxide in the absence of a complete mitochondrial electron
      transport chain, pointing to the existence of a possible non-mitochondrial source
      for ROS generation. Our results indicate that oxidative stress resulting from a
      disturbance of redox balance can play a major role in mother cell-specific
      lifespan determination of yeast cells.

PMID- 15489200
TI  - A novel assay for replicative lifespan in Saccharomyces cerevisiae.
AB  - The replicative lifespan of Saccharomyces cerevisiae is determined by both
      genetic and environmental factors. Many of the same factors determine the
      lifespan of metazoan animals. The lack of fast and reliable lifespan assays has
      limited the pace of yeast aging research. In this study we describe a novel
      strategy for assaying replicative lifespan in yeast, and apply it in a screening
      of mutants that are resistant to pro-oxidants. The assay reproduces the lifespan
      shortening effects of deleting SIR2 and of growth in the presence of paraquat, a
      pro-oxidant. The lifespan-increasing activity of resveratrol is also reproduced.
      Compared to current assays, this new strategy promises to significantly increase
      the possible number of replicative-lifespan determinations.

PMID- 15489201
TI  - Reliable high-throughput screening with Pichia pastoris by limiting yeast cell
      death phenomena.
AB  - Comparative screening of gene expression libraries employing the potent
      industrial host Pichia pastoris for improving recombinant eukaryotic enzymes by
      protein engineering was an unsolved task. We simplified the protocol for protein
      expression by P. pastoris and scaled it down to 0.5-ml cultures. Optimising
      standard growth conditions and procedures, programmed cell death and necrosis of
      P. pastoris in microscale cultures were diminished. Uniform cell growth in 96
      deep-well plates now allows for high-throughput protein expression and screening
      for improved enzyme variants. Furthermore, the change from one host for protein
      engineering to another host for enzyme production becomes dispensable, and this
      accelerates the protein breeding cycles and makes predictions for large-scale
      production more accurate.

PMID- 15489202
TI  - Selenomethionine stimulates MAPK (ERK) phosphorylation, protein oxidation, and
      DNA synthesis in gastric cancer cells.
AB  - Selenium is an essential trace element and is required for the synthesis of
      cellular enzymes that protect against oxidative stress. Epidemiological findings
      indicate that low selenium intake is associated with increased cancer risk, and,
      although the majority of studies show that exposure of transformed cells to
      selenium results in apoptotic cell death, there are reports indicating that cells
      exposure to low selenium concentrations promotes cellular proliferation. Gastric
      adenocarcinoma SNU-1 cells responded to selenomethionine with a biphasic
      proliferative curve: enhanced incorporation of 3H-thymidine into DNA within a
      very narrow range of selenomethionine concentrations followed by decreased 3H
      thymidine uptake at higher levels. Concentrations of selenomethionine that
      stimulate cellular proliferation also induce cellular oxidation and
      phosphorylation of MAPK (ERK), a component of cell signaling cascades. MAPK (ERK)
      phosphorylation is synonymous with MAPK activation and enhanced cell growth. Our
      findings support previous observations of enhanced proliferation in response to
      low levels of selenium and suggest that, at certain concentrations,
      selenomethionine induces mild oxidative stress that, in turn, stimulates DNA
      synthesis.

PMID- 15489203
TI  - Reports: plasma and dietary phytoestrogens and risk of premalignant lesions of
      the cervix.
AB  - A number of epidemiological studies have observed an inverse association between
      phytoestrogens and risk of certain hormonally dependent cancers. We undertook an
      exploratory analysis of the relationship between specific phytoestrogens and
      premalignant cervical lesions. A case-control study of 122 women with
      histologically confirmed cervical squamous intraepithelial lesions (SILs) of the
      cervix and 183 cytologically normal controls was conducted from 1992 to 1996 in
      Honolulu, Hawaii. A cervical cell sample was obtained for human papillomavirus
      (HPV) testing. Dietary information was collected using a structured survey, and a
      fasting blood sample was taken for measurement of five isoflavonoids (genistein,
      glycitein, daidzein, O-desmethylangolensin, and equol), two flavonoids
      (hesperetin and naringenin), and two lignans (enterodiol and enterolactone).
      Plasma levels of equol and enterodiol were positively associated with cervical
      SIL risk: odds ratio, OR = 6.5; 95% confidence interval, CI = 1.4-29.2; P for
      trend = 0.02 and OR = 2.7; 95% CI = 1.1-6.3; P for trend = 0.01, respectively,
      for the highest relative to the lowest quartile level after adjustment for age,
      race/ethnicity, HPV infection, cigarette smoking, alcohol drinking, and lifetime
      number of sexual partners. A nonsignificant positive association with cervical
      SIL risk was observed for plasma enterolactone. Consistent with the relationships
      observed for the plasma lignans, dietary sources of lignans, including garlic and
      taro leaves/ong choy/marunggay, were positively associated with cervical SIL
      risk. A positive association was also suggested for other lignan sources such as
      seaweed, onions, grapefruit, and seeds. This is the first study to observe a
      positive association between specific phytoestrogens and premalignancies of the
      cervix. The results of this investigation should be considered preliminary and
      need to be verified in larger, prospective studies.

PMID- 15489204
TI  - Soy and isoflavone intake are associated with reduced risk of ovarian cancer in
      southeast china.
AB  - To investigate whether intake of soy and isoflavones has an inverse association
      with ovarian cancer risk, a case-control study was conducted in Hangzhou, China.
      Cases were 254 patients with histologically confirmed epithelial ovarian cancer.
      The 652 controls comprised 340 hospital visitors, 261 non-neoplastic hospital
      outpatients, and 51 women recruited from the community. Habitual dietary intakes
      including 9 soy foods were measured by face-to-face interview using a validated
      and reliable food-frequency questionnaire. Unconditional logistic regression
      analyses were used to estimate odds ratios (ORs) and 95% confidence intervals
      (CIs) accounting for age, demographic characteristics, hormonal factors, and
      total energy intake. Intake of soy and isoflavones was inversely related to the
      risk of ovarian cancer. Compared with the highest versus the lowest quartile
      intake, the ORs were 0.50 (95% CI = 0.31-0.82) for total soy foods and 0.51 (95%
      CI = 0.31-0.85) for isoflavones. Among subgroups of soy foods and isoflavones,
      the ORs for soybeans, bean curd, daidzein, genistein, and glycitein were 0.35
      (95% CI = 0.22-0.58), 0.49 (95% CI = 0.29-0.81), 0.52 (95% CI = 0.31-0.87), 0.50
      (95% CI = 0.30-0.84), and 0.59 (95% CI = 0.35-0.97), respectively.

PMID- 15489205
TI  - Dietary habits and growth and recurrence of colorectal adenomas: results from a
      three-year endoscopic follow-up study.
AB  - Diet has been associated with sporadic colorectal cancer (CRC) risk. The
      relationship to the growth rate of adenomas is largely unknown. Previous analyses
      of our cohort of polyp cases have shown 1) indicators of a healthy diet were
      inversely associated with adenoma occurrence, 2) diet was related to the fecal
      profile, 3) obesity was positively associated with adenoma growth, 4) familial
      predisposition of CRC was positively associated with adenoma growth, and 5)
      intervention with calcium and antioxidants was not associated with adenoma
      growth. The present aim was to study the effects of diet on growth and recurrence
      of adenomas. Data were collected from a 3-yr polyp growth and intervention study.
      Polyps larger than 9 mm were removed, whereas the remainder and newly discovered
      polyps smaller than 10 mm were left in situ for 3 yr. Diet was assessed by a 5
      day dietary record by weighing (DR) and food-frequency questionnaire (FFQ). Weak
      inverse associations were found only between adenoma growth and fruits and
      berries (adjusted odds ratio, aOR = 0.3; 95% CI = 0.1-0.9) and carbohydrates (aOR
      = 0.1; 95% CI = 0.1-0.6; both only DR data) and between adenoma recurrence and
      vegetables (crude odds ratio, cOR = 0.4; 95% CI = 0.1-0.9; only FFQ data). Taken
      together, the present and previous findings from this cohort may indicate an
      early role for dietary factors in CRC development.

PMID- 15489206
TI  - Flavonoid intake in relation to lung cancer risk: case-control study among women
      in Greece.
AB  - We have examined the role of three classes of flavonoids that are relatively
      common in the Greek diet (flavanones, flavan-3-ols, and flavonols) in the
      etiology of lung cancer using data from a case-control study among women, which
      was undertaken in Athens, Greece, in the late 1980s. Study subjects were 154
      women with lung cancer and 145 control women with orthopedic conditions. Women
      reported their life-long smoking histories and average frequency of consumption,
      before onset of present disease, of 47 food items or beverages that collectively
      covered >80% of the intake of each of the energy-providing nutrients. Intakes of
      flavonoids were calculated using the recently published U.S. Department of
      Agriculture database. The data were modeled through logistic regression,
      controlling for energy intake and smoking. There was no indication that intake of
      any of the studied flavonoid categories reduces the risk of lung cancer; indeed,
      for flavonols there was an unexpected positive association. Thus, our study does
      not indicate a protective effect of flavanones, flavan-3-ols, or flavonols on
      lung cancer risk and indicates that the factors responsible for the protective
      effect of vegetables and fruits against the risk of this cancer are unlikely to
      belong to these flavonoid categories.

PMID- 15489207
TI  - Fecal water genotoxicity is predictive of tumor-preventive activities by inulin
      like oligofructoses, probiotics (Lactobacillus rhamnosus and Bifidobacterium
      lactis), and their synbiotic combination.
AB  - The measurement of fecal water genotoxicity in human colon cells could be a
      useful biomarker to study effects of diet in the colon. Here we assessed aqueous
      fecal extracts of samples from a chronic study with rats fed prebiotics,
      probiotics, and their combination. Treatments were maltodextrins (controls),
      inulin/oligofructoses (prebiotic), Lactobacillus rhamnosus, and Bifidobacterium
      lactis (probiotics) or both (synbiotic). Azoxymethane (AOM) was administered to
      initiate tumors. Rat feces were collected at 0 and 10 days and 2, 4, and 8 mo,
      and cecal contents were collected at 8 mo. Aqueous phases were prepared and
      tested for genotoxicity in HT29 colon cells using the comet assay. The studied
      types of intervention reduced fecal and cecal genotoxicity. DNA damage by samples
      from AOM-treated, tumor-free rats was significantly lower than from tumor-bearing
      animals, especially after 4 mo of synbiotic and prebiotic interventions. Inulin
      based diets reduced exposure to genotoxins in the feces, directly reflecting the
      reported reduction of tumor incidence in these animals. Evidence is provided for
      the validity of this measurement as a biomarker of chemoprevention because 1)
      fecal water genotoxicity reflected genotoxic exposure in the cecum, 2) tumor
      incidence and fecal genotoxicity were directly related, and 3) these
      interventions reduced tumor risks by reducing exposure to genotoxins in the gut.

PMID- 15489208
TI  - Nutritional consequences of radiotherapy in nasopharynx cancer patients.
AB  - Nasopharynx cancer (NPC) occurs frequently in southern China. Radiotherapy (RT)
      is the standard treatment for this cancer, and weight loss is commonly observed
      during and for a prolonged period after RT. The determinants of this phenomenon
      are not well known. The nutritional status of 38 NPC patients was assessed
      serially before and for a 6-mo period after RT. Body weight, body composition (by
      dual X-ray absorptiometry), basal metabolic rate (BMR, by indirect calorimetry),
      and calorie intake (by 3-day dietary record) were documented at pre-RT (T0), end
      RT (T1), 2 mo post-end-RT (T2), and 6 mo post-end-RT (T3). The BMI at end-RT was
      21.5 +- 3.7 kg/m2 (range = 13.7-27.9 kg/m2) and was significantly lower than that
      at pre-RT (P < 0.001). Body weight at T1-T3 was significantly lower than that at
      T0 (P < 0.001). Mean percentage weight loss was 10.8% at end-RT. Fifty-five
      percent of patients (20 of 30) had 10% weight loss by the end of RT. BMR
      corrected for body weight did not change significantly among the four time
      points, but BMRs corrected for lean body mass at T2 and T3 were significantly
      lower than that at T0 (P < 0.01). Patients' calorie intake generally declined
      from T0 to T1 (from 1,857 P < 411 kcal to 11,68 +- 549 kcal, P < 0.001) and then
      increased from T1 to T3. The calorie intakes at T2 and T3 were not significantly
      different from that at T0 but were significantly higher than that at T1. Patients
      were in negative energy balance before, during, and up until 6 mo after RT. The
      recovery in body weight lagged behind the recovery of dietary intake. Eighty-two
      percent of NPC patients had significant weight loss and was in negative energy
      balance at the end of RT, which persisted for at least 6 mo. This finding
      suggests that there is room for improvement in the nutritional status of patients
      with NPC treated with RT.

PMID- 15489209
TI  - Dietary iron promotes azoxymethane-induced colon tumors in mice.
AB  - There is accumulating evidence that high levels of dietary iron may play a role
      in colon carcinogenesis. We used a mouse model to investigate the impact of
      elevated dietary iron on incidence of aberrant crypt foci (ACF; a preneoplastic
      lesion) on tumor formation and on induction of oxidative stress. A/J mice were
      injected intraperitoneally, once a week for 6 weeks, with the colonotropic
      carcinogen, azoxymethane (AOM) or saline (vehicle controls). Following AOM or
      saline treatments, mice were placed on diets of high (3,000 ppm) and low (30 ppm)
      iron. Mice in each treatment group were sacrificed at 6 and 10 weeks following
      the final injection with AOM or saline. Colons were removed for subsequent
      histopathological analysis, which revealed average increases of 4.6 +- 1.3 vs.
      10.4 +- 2.5 total tumors at 6 weeks and 30.75 +- 2.7 vs. 41.5 +- 4.4 total tumors
      at 10 weeks per AOM-treated mouse on low- and high-iron diets, respectively.
      There were no significant differences in incidence of ACF attributable to iron,
      although there was a trend toward greater crypt multiplicity per focus in mice on
      high-iron diets. Notably, no tumors were observed in mice receiving vehicle
      control injections in place of carcinogen, regardless of the level of dietary
      iron. These data suggest that iron exerts its effect at the stage of tumor
      promotion, but is not sufficient to initiate tumor formation. To learn more about
      mechanisms by which iron promotes tumor growth, colons were assayed for several
      biomarkers of oxidative stress [BOS; total F2-isoprostanes (F2-IsoPs), 15-F2t
      isoprostanes (8-IsoPGF2s), Isofurans (IsoFs), and 8-hydroxyguanosines (8
      OH[d]Gs)], as well as iron absorption, programmed cell death, and cellular
      proliferation. Elevated PCNA and TUNEL staining of the colon epithelium revealed
      hyperproliferative and apoptotic responses to iron, while no significant
      differences between iron groups were observed in each of the BOS that were
      assayed. Our results suggest that, following carcinogen exposure, elevated
      dietary iron promotes the growth of tumors with altered cellular homeostasis
      through a mechanism that is independent of oxidative stress.

PMID- 15489210
TI  - Extract of Kurosu, a vinegar from unpolished rice, inhibits azoxymethane-induced
      colon carcinogenesis in male F344 rats.
AB  - The modifying effects of administering an ethyl acetate extract of Kurosu (EK), a
      vinegar made from unpolished rice, in drinking water on the development of
      azoxymethane (AOM)-induced colon carcinogenesis were investigated in male F344
      rats. Animals were given 2 weekly subcutaneous injections of AOM (20 mg/kg body
      weight). They also received drinking water containing 0%, 0.05%, or 0.1% EK for
      35 wk, starting 1 wk after the last dosing of AOM. EK administration
      significantly inhibited the incidence and multiplicity of colon adenocarcinoma (P
      < 0.05), compared with those in the AOM alone group. These findings suggest that
      EK may be effective for inhibiting colon carcinogenesis.

PMID- 15489211
TI  - Methyl selenium-induced vascular endothelial apoptosis is executed by caspases
      and principally mediated by p38 MAPK pathway.
AB  - The induction of vascular endothelial cell apoptosis and inhibition of tumor
      associated angiogenesis by selenium may contribute to its cancer chemopreventive
      effects. Here we examined the stress-activated/mitogen-activated protein kinases
      (p38 MAPK, ERK1/2) and protein kinase B/AKT as potential signaling mediators for
      apoptosis induction by a methylselenol precursor methylseleninic acid (MSeA) in
      human umbilical vein endothelial cells (HUVEC). Time course experiments showed
      that p38 MAPK hyperphosphorylation and ERK1/2 dephosphorylation occurred before
      the cleavage of procaspase-3 and poly(ADP-ribose) polymerase (PARP), whereas AKT
      dephosphorylation occurred after caspase activation. The p38 MAPK inhibitor
      SB202190 attenuated the MSeA-induced morphological changes and decreased DNA
      fragmentation and the cleavage of procaspase-3 and PARP in concordant
      proportions. The general caspase inhibitor zVADfmk completely blocked the MSeA
      induced PARP cleavage and DNA fragmentation, whereas zDEVDfmk, an inhibitor for
      caspase-3-like activities, was nearly as effective for inhibiting apoptosis. In
      comparison, apoptosis induced by selenite in HUVECs was observed in the complete
      absence of an activation of the major caspases. Taken together, the data support
      p38 MAPK as a key upstream mediator for the methylselenol-specific induction of
      vascular endothelial caspase-dependent apoptosis, which is principally executed
      by caspase-3-like activities.

PMID- 15489212
TI  - Cytotoxicity and antiproliferative activities of several phenolic compounds
      against three melanocytes cell lines: relationship between structure and
      activity.
AB  - Polyphenolic compounds are widely distributed in the vegetable kingdom and are
      therefore consumed regularly in the human diet. Epidemiological studies suggest
      that foods rich in polyphenolic compounds contribute to reducing the risk of
      cancer. The purpose of our work is to: 1) study the possible cytotoxicity and
      antiproliferative effects of 13 polyphenolic compounds on 3 cell lines of
      melanocytes, 2 of melanoma (B16F10 and SK-MEL-1), and 1 of nontransformed
      melanocytes (Melan-a); and 2) identify the possible relationship between the
      chemical structure of the tested compounds and their effect on cellular
      viability. The said polyphenolic compounds corresponded to 8 flavonoids with
      varying hydroxyl and methoxyl substituents, related structurally through the
      oxidation state of their flavonoid skeleton, a catechin polymer and 4 phenolic
      acids. The cytotoxic activity of all the studied compounds was modest or not
      apparent. The flavonoids luteolin, tangeretin, baicalein, quercetin, and
      myricetin, and gallic acid showed antiproliferative effects on the tested lines.
      Our results suggest that a correlation exists between the structural oxidation
      state and the position, number, and nature of substituents of the polyphenolic
      compounds studied and their antiproliferative effects.

PMID- 15489213
TI  - Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro.
AB  - Prostate cancer is an important public health problem in the United States. Seven
      phytoestrogens found in common herbal products were screened for estrogen
      receptor binding and growth inhibition of androgen-insensitive (PC-3) and
      androgen-sensitive (LNCaP) human prostate tumor cells. In a competitive 3H
      estradiol ligand binding assay using mouse uterine cytosol, 2.5 M quercetin,
      baicalein, genistein, epigallocatechin gallate (EGCG), and curcumin displaced >
      85% of estradiol binding, whereas apigenin and resveratrol displaced > 40%. From
      growth inhibition studies in LNCaP cells, apigenin and curcumin were the most
      potent inhibitors of cell growth, and EGCG and baicalein were the least potent.
      In PC-3 cells, curcumin was the most potent inhibitor of cell growth, and EGCG
      was the least potent. In both cell lines, significant arrest of the cell cycle in
      S phase was induced by resveratrol and EGCG and in G2M phase by quercetin,
      baicalein, apigenin, genistein, and curcumin. Induction of apoptosis was induced
      by all of the 7 compounds in the 2 cell lines as shown by TUNEL and DNA
      fragmentation assays. Androgen responsiveness of the cell lines did not correlate
      with cellular response to the phytoestrogens. In conclusion, these 7
      phytoestrogens, through different mechanisms, are effective inhibitors of
      prostate tumor cell growth.

PMID- 15489214
TI  - Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition
      of Akt/NF-kappaB signaling.
AB  - Ganoderma lucidum (Reishi, Lingzhi) is a popular Asian mushroom that has been
      used for more than 2 millennia for the general promotion of health and was
      therefore called the "Mushroom of Immortality." Ganoderma lucidum was also used
      in traditional Chinese medicine to prevent or treat a variety of diseases,
      including cancer. We previously demonstrated that Ganoderma lucidum suppresses
      the invasive behavior of breast cancer cells by inhibiting the transcription
      factor NF-kappaB. However, the molecular mechanisms responsible for the
      inhibitory effects of Ganoderma lucidum on the growth of highly invasive and
      metastatic breast cancer cells has not been fully elucidated. Here, we show that
      Ganoderma lucidum inhibits proliferation of breast cancer MDA-MB-231 cells by
      downregulating Akt/NF-kappaB signaling. Ganoderma lucidum suppresses
      phosphorylation of Akt on Ser473 and downregulates the expression of Akt, which
      results in the inhibition of NF-kappaB activity in MDA-MB-231 cells. The
      biological effect of Ganoderma lucidum was demonstrated by cell cycle arrest at
      G0/G1, which was the result of the downregulation of expression of NF-kappaB
      regulated cyclin D1, followed by the inhibition of cdk4. Our results suggest that
      Ganoderma lucidum inhibits the growth of MDA-MB-231 breast cancer cells by
      modulating Akt/NF-kappaB signaling and could have potential therapeutic use for
      the treatment of breast cancer.

PMID- 15489215
TI  - Quality evaluation of commercial extracts of Scutellaria baicalensis.
AB  - Botanical products have been widely used for various illnesses and general well
      being. However, quality control of botanical products is often not performed due
      to lack of standardization, resulting in inconsistent efficacies and sometimes
      serious toxicity. The goals of this study were to determine the correlation
      between chemical composition and biological activities and to establish a method
      to measure authenticity, chemical consistency, and biological potency of
      botanical products. A high-performance liquid chromatography method was used to
      analyze the authenticity and chemical composition of 10 different commercial
      extracts. The cell viability assay and prostaglandin E2 (PGE2) enzyme immunoassay
      were used to analyze biological potency and consistency. Our results showed all
      extracts contained marker components (baicalein and/or baicalin), confirming
      their authenticity. However, significant product-to-product and batch-to-batch
      variation of these marker components was observed with 4 products containing no
      baicalin at all and baicalein concentration ranging from 0 to 52.3 g/mg. The 50%
      growth inhibition concentration of the extracts ranged from 0.18 to 2.0 mg/ml,
      more than an 11-fold variation. PGE2 levels varied from 19.5 to 111.1 pg/106
      cells, more than a 5.7-fold difference. These results demonstrated significant
      variation in chemical composition and biological activities of the commercial
      extracts and that the amount of marker components may not reflect biological
      activity levels. Therefore, chemical analysis alone is inadequate for quality
      control, and biological assays must be included for botanical products to ensure
      chemical authenticity as well as pharmacological/biological potency and
      consistency.

PMID- 15489217
TI  - The metabolic syndrome in obese postmenopausal women: relationship to body
      composition, visceral fat, and inflammation.
AB  - The purpose of this study was to investigate whether aerobic fitness, body
      composition, body fat distribution, and inflammation are different in obese
      postmenopausal women with and without the metabolic syndrome (MS), and whether
      the severity of MS is associated with these characteristics. Fifty-eight women
      (age, 59 +/- 1 yr; body mass index, 33.0 +/- 0.6 kg/m2)completed testing of
      maximal aerobic capacity, body composition (fat mass, lean mass, and percent body
      fat), body fat distribution (sc and visceral fat areas, and regional adipocyte
      sizes), and inflammation (C-reactive protein, IL-6, and TNF-alpha,and their
      soluble receptors). Lean mass (44.4 +/- 0.9 vs. 41.2 +/- 0.9 kg; P < 0.05),
      visceral fat area (180 +/- 10 vs. 135 +/- 7 cm2; P <0.001), and plasma soluble
      TNF receptor 1 (sTNFR1; 860 +/- 25 vs. 765 +/- 42 pg/ml; P < 0.05) were higher in
      women with the MS(n = 27) than in those without the MS (n = 31). The number of MS
      components was directly related to weight, body mass index, fat mass, lean mass,
      visceral fat area, and plasma sT-NFR1. We conclude that obese older women with
      the MS are characterized by high lean mass, high visceral fat, and elevated
      sTNFR1, and the severity of the MS is associated with body composition, visceral
      adiposity, and inflammation.

PMID- 15489218
TI  - Functional overlap between ABCD1 (ALD) and ABCD2 (ALDR) transporters: a
      therapeutic target for X-adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative disease
      caused by loss of function of the peroxisomal transporter ABCD1 (ALD), which
      results in accumulation of very long chain fatty acids (VLCFAs) in organs and
      serum, central demyelination and peripheral axonopathy and Addison's disease.
      Knockout of the ALD gene in the mouse (ALD(-)) results in an
      adrenomyeloneuropathy-like disease (a late onset form of X-ALD). In the present
      study, we demonstrate that axonal damage occurs as first pathological event in
      this model, followed by myelin degeneration. We show that this phenotype can be
      modulated through expression levels of an ALD-related gene (ALDR/ABCD2), its
      closest paralogue and a target of PPARalpha and SREBP transcription factors.
      Overexpression of ALDR in ALD(-) mice prevents both VLCFAs accumulation and the
      neurodegenerative features, whereas double mutants for ALD and ALDR exhibit an
      earlier onset and more severe disease (including signs of inflammatory reaction)
      when compared with ALD single mutants. Thus, our results provide direct evidence
      for functional redundancy/overlap between both transporters in vivo and highlight
      ALDR as therapeutic target for treatment of X-ALD.

PMID- 15489219
TI  - Case-control study and transmission disequilibrium test provide consistent
      evidence for association between schizophrenia and genetic variation in the 22q11
      gene ZDHHC8.
AB  - Genetic variants in the 22q11 gene ZDHHC8, which encodes a putative transmembrane
      palmitoyltransferase, has been associated to schizophrenia in family-based
      linkage disequilibrium (LD) studies. The single nucleotide polymorphism (SNP)
      rs175174 (A/G), which had the strongest association, has been shown recently to
      regulate the level of the fully functional transcript by modulating the retention
      of intron 4 of ZDHHC8. In this work, we genotyped three genetic variants within
      the ZDHHC8 locus and conducted association studies in both population- and family
      based samples of the Han Chinese population. The three polymorphisms spanning
      approximately 5.5 Kb were detected to be in significant LD. Our results provided
      compelling supportive evidence for association of the variants within the ZDHHC8
      locus with schizophrenia but revealed different risk allele at SNP rs175174. The
      G allele was significantly more common in cases than in controls (69.47 : 59.96%;
      P=0.000018) and excess transmission of the same allele was confirmed in the
      family-based transmission disequilibrium test (transmitted/non-transmitted=87 :
      54; P=0.0055). Both sample sets even shared the same risk haplotype with similar
      frequency. Our current data presents consistent association results obtained from
      both case-control and family-based samples in a same laboratory under the same
      experimental condition. Despite the potential genetic heterogeneity, our
      independent findings further support that the 22q11 region is likely to harbor
      candidate schizophrenia susceptibility genes.

PMID- 15489220
TI  - Constitutive protease-activated receptor-2-mediated migration of MDA MB-231
      breast cancer cells requires both beta-arrestin-1 and -2.
AB  - Protease-activated receptor-2 (PAR-2) is activated by trypsin-like serine
      proteases and can promote cell migration through an ERK1/2-dependent pathway,
      involving formation of a scaffolding complex at the leading edge of the cell.
      Previous studies also showed that expression of a dominant negative fragment of
      beta-arrestin-1 reduces PAR-2-stimulated internalization, ERK1/2 activation, and
      cell migration; however, this reagent may block association of many proteins,
      including beta-arrestin-2 with clathrin-coated pits. Here we investigate the role
      of PAR-2 in the constitutive migration of a metastatic breast cancer cell line,
      MDA MB-231, and use small interfering RNA to determine the contribution of each
      beta-arrestin to this process. We demonstrate that a trypsin-like protease
      secreted from MDA MB-231 cells can promote cell migration through autocrine
      activation of PAR-2 and this correlates with constitutive localization of PAR-2,
      beta-arrestin-2, and activated ERK1/2 to pseudopodia. Addition of MEK-1
      inhibitors, trypsin inhibitors, a scrambled PAR-2 peptide, and silencing of beta
      arrestins with small interfering RNA also reduce base-line migration of MDA MB
      231 cells. In contrast, a less metastatic PAR-2 expressing breast cancer cell
      line does not exhibit constitutive migration, pseudopodia formation, or trypsin
      secretion; in these cells PAR-2 is more uniformly distributed around the cell
      periphery. These data demonstrate a requirement for both beta-arrestins in PAR-2
      mediated motility and suggest that autocrine activation of PAR-2 by secreted
      proteases may contribute to the migration of metastatic tumor cells through beta
      arrestin-dependent ERK1/2 activation.

PMID- 15489221
TI  - Doxorubicin activates ATM-dependent phosphorylation of multiple downstream
      targets in part through the generation of reactive oxygen species.
AB  - The requirement for the serine/threonine protein kinase ATM in coordinating the
      cellular response to DNA damage induced by ionizing radiation has been studied
      extensively. Many of the anti-tumor chemotherapeutics in clinical use today cause
      DNA double strand breaks; however, few have been evaluated for their ability to
      modulate ATM-mediated pathways. We have investigated the requirement for ATM in
      the cellular response to doxorubicin, a topoisomerase II-stabilizing drug. Using
      several ATM-proficient and ATM-deficient cell lines, we have observed ATM
      dependent nuclear accumulation of p53 and ATM-dependent phosphorylation of p53 on
      seven serine residues. This was accompanied by an increased binding of p53 to its
      cognate binding site, suggesting transcriptional competency of p53 to activate
      its downstream effectors. Treatment of cells with doxorubicin led to the
      phosphorylation of histone H2AX on serine 139 with dependence on ATM for the
      initial response. Doxorubicin treatment also stimulated ATM autophosphorylation
      on serine 1981 and the ATM-dependent phosphorylation of numerous effectors in the
      ATM-signaling pathway, including Nbs1 (Ser(343)), SMC1 (Ser(957)), Chk1 (Ser(317)
      and Ser(345)), and Chk2 (Ser(33/35) and Thr(68)). Although generally classified
      as a topoisomerase II-stabilizing drug that induces DNA double strand breaks,
      doxorubicin can intercalate DNA and generate reactive oxygen species.
      Pretreatment of cells with the superoxide scavenger ascorbic acid had no effect
      on the doxorubicin-induced phosphorylation and accumulation of p53. In contrast,
      preincubation of cells with the hydroxyl radical scavenger, N-acetylcysteine,
      significantly attenuated the doxorubicin-mediated phosphorylation and
      accumulation of p53, p53-DNA binding, and the phosphorylation of H2AX, Nbs1,
      SMC1, Chk1, and Chk2, suggesting that hydroxyl radicals contribute to the
      doxorubicin-induced activation of ATM-dependent pathways.

PMID- 15489222
TI  - Leucine culture reveals that ATP synthase functions as a fuel sensor in
      pancreatic beta-cells.
AB  - Our goal was to investigate whether leucine culture affects beta-cell glucose
      sensing. One-day culture of rat islets with 10 mM leucine had no effect on
      glucose-induced insulin secretion. One-week leucine culture decreased the
      threshold for glucose-induced insulin secretion and increased maximal insulin
      secretion at 30 mM glucose. Glucose-induced cytosolic free Ca(2+) was increased
      at 1 week but not at 1 day of leucine culture. Without glucose, ATP content was
      not different with or without leucine culture for 1 week. With 20 mM glucose, ATP
      content was higher by 1.5-fold in islets cultured for 1 week with leucine than
      those without leucine. Microarray experiments indicated that culture of RINm5F
      cells with leucine increased expression of ATP synthase beta subunit 3.2-fold,
      which was confirmed by real time reverse transcription-PCR analysis (3.0- +/- 0.4
      fold) in rat islets at 1 week but not after 1 day with leucine culture. Down
      regulation of ATP synthase beta subunit by siRNA decreased INS1 cell ATP content
      and insulin secretion with 20 mM glucose. Overexpression of ATP synthase beta
      subunit in INS1 cell increased insulin secretion in the presence of 5 and 20 mM
      glucose. In conclusion, one-week leucine culture of rat islets up-regulated ATP
      synthase and increased ATP content, which resulted in elevated [Ca(2+)] levels
      and more insulin exocytosis by glucose. Depletion of ATP synthase beta subunit
      with siRNA produced opposite effects. These data reveal the fuel-sensing role of
      mitochondrial ATP synthase in the control of ATP production from glucose and the
      control of glucose-induced insulin secretion.

PMID- 15489223
TI  - Nedd4-2 functionally interacts with ClC-5: involvement in constitutive albumin
      endocytosis in proximal tubule cells.
AB  - Constitutive albumin uptake by the proximal tubule is achieved by a receptor
      mediated process in which the Cl(-) channel, ClC-5, plays an obligate role. Here
      we investigated the functional interaction between ClC-5 and ubiquitin ligases
      Nedd4 and Nedd4-2 and their role in albumin uptake in opossum kidney proximal
      tubule (OK) cells. In vivo immunoprecipitation using an anti-HECT antibody
      demonstrated that ClC-5 bound to ubiquitin ligases, whereas glutathione S
      transferase pull-downs confirmed that the C terminus of ClC-5 bound both Nedd4
      and Nedd4-2. Nedd4-2 alone was able to alter ClC-5 currents in Xenopus oocytes by
      decreasing cell surface expression of ClC-5. In OK cells, a physiological
      concentration of albumin (10 mug/ml) rapidly increased cell surface expression of
      ClC-5, which was also accompanied by the ubiquitination of ClC-5. Albumin uptake
      was reduced by inhibiting either the lysosome or proteasome. Total levels of
      Nedd4-2 and proteasome activity also increased rapidly in response to albumin.
      Overexpression of ligase defective Nedd4-2 or knockdown of endogenous Nedd4-2
      with small interfering RNA resulted in significant decreases in albumin uptake.
      In contrast, pathophysiological concentrations of albumin (100 and 1000 mug/ml)
      reduced the levels of ClC-5 and Nedd4-2 and the activity of the proteasome to the
      levels seen in the absence of albumin. These data demonstrate that normal
      constitutive uptake of albumin by the proximal tubule requires Nedd4-2, which may
      act via ubiquitination to shunt ClC-5 into the endocytic pathway.

PMID- 15489224
TI  - Cdk5/p35 phosphorylates mSds3 and regulates mSds3-mediated repression of
      transcription.
AB  - Cyclin-dependent kinase 5 (Cdk5), a serine/threonine kinase that displays kinase
      activity predominantly in neurons, is activated by two non-cyclin activators, p35
      or p39. Here, we report a physical and functional interaction between the
      Cdk5/p35 complex and mouse Sds3 (mSds3), an essential component of mSin3-histone
      deacetylase (HDAC) co-repressor complex. mSds3 binds to p35 both in vitro and in
      vivo, enabling active Cdk5 to phosphorylate mSds3 at serine 228. A mSds3 S228A
      mutant retained mSin3 binding activity, but its dimerization was not greatly
      enhanced by p35 when compared with wild type. Notably, p35 overexpression
      augmented mSds3-mediated transcriptional repression in vitro. Interestingly,
      mutational studies revealed that the ability of exogenous mSds3 to rescue cell
      growth and viability in mSds3 null cells correlates with its ability to be
      phosphorylated by Cdk5. The identification of mSds3 as a substrate of the
      Cdk5/p35 complex reveals a new regulatory mechanism in controlling the mSin3-HDAC
      transcriptional repressor activity and provides a new potential therapeutic means
      to inhibit specific HDAC activities in disease.

PMID- 15489225
TI  - Fluorescence resonance energy transfer reports properties of syntaxin1a
      interaction with Munc18-1 in vivo.
AB  - Syntaxin1A, a neural-specific N-ethylmaleimide-sensitive factor attachment
      protein receptor protein essential to neurotransmitter release, in isolation
      forms a closed conformation with an N-terminal alpha-helix bundle folded upon the
      SNARE motif (H3 domain), thereby limiting interaction of the H3 domain with
      cognate SNAREs. Munc18-1, a neural-specific member of the Sec1/Munc18 protein
      family, binds to syntaxin1A, stabilizing this closed conformation. We used
      fluorescence resonance energy transfer (FRET) to characterize the Munc18
      1/syntaxin1A interaction in intact cells. Enhanced cyan fluorescent protein
      Munc18-1 and a citrine variant of enhanced yellow fluorescent protein-syntaxin1A,
      or mutants of these proteins, were expressed as donor and acceptor pairs in human
      embryonic kidney HEK293-S3 and adrenal chromaffin cells. Apparent FRET efficiency
      was measured using two independent approaches with complementary results that
      unambiguously verified FRET and provided a spatial map of FRET efficiency. In
      addition, enhanced cyan fluorescent protein-Munc18-1 and a citrine variant of
      enhanced yellow fluorescent protein-syntaxin1A colocalized with a Golgi marker
      and exhibited FRET at early expression times, whereas a strong plasma membrane
      colocalization, with similar FRET values, was apparent at later times.
      Trafficking of syntaxin1A to the plasma membrane was dependent on the presence of
      Munc18-1. Both syntaxin1A(L165A/E166A), a constitutively open conformation
      mutant, and syntaxin1A(I233A), an H3 domain point mutant, demonstrated apparent
      FRET efficiency that was reduced approximately 70% from control. In contrast, the
      H3 domain mutant syntaxin1A(I209A) had no effect. By using phosphomimetic mutants
      of Munc18-1, we also established that Ser-313, a Munc18-1 protein kinase C
      phosphorylation site, and Thr-574, a cyclin-dependent kinase 5 phosphorylation
      site, regulate Munc18-1/syntaxin1A interaction in HEK293-S3 and chromaffin cells.
      We conclude that FRET imaging in living cells may allow correlated regulation of
      Munc18-1/syntaxin1A interactions to Ca(2+)-regulated secretory events.

PMID- 15489226
TI  - Thermodynamic studies on the interaction of the third complement component and
      its inhibitor, compstatin.
AB  - Compstatin is a 13-residue cyclic peptide that inhibits complement activation by
      binding to complement component, C3. Although the activity of compstatin has been
      improved severalfold using combinatorial and rational design approaches, the
      molecular basis for its interaction with C3 is not yet fully understood. In the
      present study, isothermal titration calorimetry was employed to dissect the
      molecular forces that govern the interaction of compstatin with C3 using four
      different compstatin analogs. Our studies indicate that the C3-compstatin
      interaction is an enthalpy-driven process. Substitution of the valine and
      histidine residues at positions 4 and 9 with tryptophan and alanine,
      respectively, resulted in the increase of enthalpy of the interaction, thereby
      increasing the binding affinity for C3. The data also suggest that the
      interaction is mediated by water molecules. These interfacial water molecules
      could be the source for unfavorable entropy and large negative heat capacity
      changes observed in the interaction. Although part of the negative heat capacity
      changes could be accounted for by the water molecules, the rest might be
      resulting from the conformational changes in C3 and/or compstatin up on binding.
      Finally, we propose based on the pK(a) values determined from the protonation
      studies that histidine on compstatin participates in protonation changes and
      contributes to the specificity of the interaction between compstatin and C3.
      These protonation changes vary significantly between the binding of different
      compstatin analogs to C3.

PMID- 15489227
TI  - Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at
      serine 536 is mediated by multiple protein kinases including I{kappa}B kinase
      (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)
      binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding
      protein-associated factor II31-mediated interleukin-8 transcription.
AB  - Phosphorylation of NF-kappaB p65(RelA) serine 536 is physiologically induced in
      response to a variety of proinflammatory stimuli, but the responsible pathways
      have not been conclusively unraveled, and the function of this phosphorylation is
      largely elusive. In contrast to previous studies, we found no evidence for a role
      of c-Jun N-terminal kinase, p38 kinase, extracellular signal-regulated kinase, or
      phosphatidylinositol 3-kinase in interleukin-1- or tumor necrosis factor-induced
      Ser-536 phosphorylation, as revealed by pharmacological inhibitors. We were not
      able to suppress Ser-536 phosphorylation by either RNA interference directed at
      IkappaB kinase (IKK)-alpha/beta (the best characterized Ser-536 kinases so far)
      or the IKKbeta inhibitor SC-514 or dominant negative mutants of either IKK. A
      green fluorescent protein p65 fusion protein was phosphorylated at Ser-536 in the
      absence of IKK activation, suggesting the existence of IKKalpha/beta-independent
      Ser-536 kinases. Chromatographic fractionation of cell extracts allowed the
      identification of two distinct enzymatic activities phosphorylating Ser-536. Peak
      1 represents an unknown kinase, whereas peak 2 contained IKKalpha, IKKbeta,
      IKKepsilon, and TBK1. Overexpressed IKKepsilon and TBK1 phosphorylate Ser-536 in
      vivo and in vitro. Reconstitution of mutant p65 proteins in p65-deficient
      fibroblasts that either mimicked phosphorylation (S536D) or preserved a predicted
      hydrogen bond between Ser-536 and Asp-533 (S536N) revealed that phosphorylation
      of Ser-536 favors interleukin-8 transcription mediated by TATA-binding protein
      associated factor II31, a component of TFIID. In the absence of phosphorylation,
      the hydrogen bond favors binding of the corepressor amino-terminal enhancer of
      split to the p65 terminal transactivation domain. Collectively, our results
      provide evidence for at least five kinases that converge on Ser-536 of p65 and a
      novel function for this phosphorylation site in the recruitment of components of
      the basal transcriptional machinery to the interleukin-8 promoter.

PMID- 15489228
TI  - Swelling-activated Ca2+ entry via TRPV4 channel is defective in cystic fibrosis
      airway epithelia.
AB  - The vertebrate transient receptor potential cationic channel TRPV4 has been
      proposed as an osmo- and mechanosensor channel. Studies using knock-out animal
      models have further emphasized the relevance of the TRPV4 channel in the
      maintenance of the internal osmotic equilibrium and mechanosensation. However, at
      the cellular level, there is still one important question to answer: does the
      TRPV4 channel generate the Ca(2+) signal in those cells undergoing a Ca(2+)
      dependent regulatory volume decrease (RVD) response? RVD in human airway
      epithelia requires the generation of a Ca(2+) signal to activate Ca(2+)-dependent
      K(+) channels. The RVD response is lost in airway epithelia affected with cystic
      fibrosis (CF), a disease caused by mutations in the cystic fibrosis transmembrane
      conductance regulator channel. We have previously shown that the defective RVD in
      CF epithelia is linked to the lack of swelling-dependent activation of Ca(2+)
      dependent K(+) channels. In the present study, we show the expression of TRPV4 in
      normal human airway epithelia, where it functions as the Ca(2+) entry pathway
      that triggers the RVD response after hypotonic stress, as demonstrated by TRPV4
      antisense experiments. However, cell swelling failed to trigger Ca(2+) entry via
      TRPV4 channels in CF airway epithelia, although the channel's response to a
      specific synthetic activator, 4 alpha-phorbol 12,13-didecanoate, was maintained.
      Furthermore, RVD was recovered in CF airway epithelia treated with 4 alpha
      phorbol 12,13-didecanoate. Together, these results suggest that defective RVD in
      CF airway epithelia might be caused by the absence of a TRPV4-mediated Ca(2+)
      signal and the subsequent activation of Ca(2+)-dependent K(+) channels.

PMID- 15489229
TI  - Structural evidence that the 32-kilodalton lipoprotein (Tp32) of Treponema
      pallidum is an L-methionine-binding protein.
AB  - A structure-to-function approach was undertaken to gain insights into the
      potential function of the 32-kDa membrane lipoprotein (Tp32) of Treponema
      pallidum, the syphilis bacterium. The crystal structure of rTp32 (determined at a
      resolution of 1.85 A) shows that the organization of rTp32 is similar to other
      periplasmic ligand-binding proteins (PLBPs), in that it consists of two
      alpha/beta domains, linked by two crossovers, with a binding pocket between them.
      In the pocket, a molecule of L-methionine was detected in the electron density
      map. Residues from both domains interact with the ligand. One of the crossover
      regions is comprised of a 3(10)-helix, a feature not typical in other ligand
      binding proteins. Sequence comparison shows strong similarity to other
      hypothetical methionine-binding proteins. Together, the data support the notion
      that rTp32 is a component of a periplasmic methionine uptake transporter system
      in T. pallidum.

PMID- 15489230
TI  - Conversion of arginine into ornithine by advanced glycation in senescent human
      collagen and lens crystallins.
AB  - Long lived proteins undergo age-related postsynthetic modifications that
      destabilize them by altering their conformation, charge, and helicity, thereby
      enhancing their resistance toward proteolysis and propensity to aggregate. The
      unexpected finding of substantial amounts of ornithine, the nonprotein amino
      acid, and decarbamidation product of arginine in acid hydrolysates of lens
      crystallins and skin collagen led us to investigate its source and mechanism of
      formation. In order to exclude ornithine formation as an artifact of acid
      hydrolysis, proteins were reductively alkylated with formaldehyde to convert
      ornithine to dimethyl-ornithine. The proteins were assayed for carboxymethyl
      ornithine and glycated ornithine ("furornithine") by liquid chromatography
      coupled to electrospray ionization mass spectrometry. Ornithine in acid
      hydrolysates of human lens and skin proteins increased from 1 to 15 nmol/mg
      protein from ages 10 to 90 years, whereas dimethyl-ornithine increased from 0.5
      to 15 and from 0 to 5 nmol/mg protein, respectively. Carboxymethyl-ornithine and
      furornithine increased with age in lens and skin from approximately 0 to 60 and 0
      to 180 pmol/mg protein, respectively. In collagen, ornithine was elevated above
      levels of nondiabetic controls only when both diabetes and end stage renal
      disease were present. The age-related increase of these modifications provides
      evidence for substantial in vivo formation of ornithine in aging human tissue
      proteins. The mechanism of ornithine formation is not known, but data suggest
      that arginine-derived advanced glycation end products might serve as precursors
      for the in vivo conversion of ornithine from arginine.

PMID- 15489231
TI  - Protein sequence analysis, cloning, and expression of flammutoxin, a pore-forming
      cytolysin from Flammulina velutipes. Maturation of dimeric precursor to monomeric
      active form by carboxyl-terminal truncation.
AB  - Flammutoxin (FTX), a 31-kDa pore-forming cytolysin from Flammulina velutipes, is
      specifically expressed during the fruiting body formation. We cloned and
      expressed the cDNA encoding a 272-residue protein with an identical N-terminal
      sequence with that of FTX but failed to obtain hemolytically active protein.
      This, together with the presence of multiple FTX family proteins in the mushroom,
      prompted us to determine the complete primary structure of FTX by protein
      sequence analysis. The N-terminal 72 and C-terminal 107 residues were sequenced
      by Edman degradation of the fragments generated from the alkylated FTX by
      enzymatic digestions with Achromobacter protease I or Staphylococcus aureus V8
      protease and by chemical cleavages with CNBr, hydroxylamine, or 1% formic acid.
      The central part of FTX was sequenced with a surface-adhesive 7-kDa fragment,
      which was generated by a tryptic digestion of FTX and recovered by rinsing the
      wall of a test tube with 6 M guanidine HCl. The 7-kDa peptide was cleaved with 12
      M HCl, thermolysin, or S. aureus V8 protease to produce smaller peptides for
      sequence analysis. As a result, FTX consisted of 251 residues, and protein and
      nucleotide sequences were in accord except for the lack of the initial Met and
      the C-terminal 20 residues in protein. Recombinant FTX (rFTX) with or without the
      C-terminal 20 residues (rFTX271 or rFTX251, respectively) was prepared to study
      the maturation process of FTX. Like natural FTX, rFTX251 existed as a monomer in
      solution and assembled into an SDS-stable, ring-shaped pore complex on human
      erythrocytes, causing hemolysis. In contrast, rFTX271, existing as a dimer in
      solution, bound to the cells but failed to form pore complex. The dimeric rFTX271
      was converted to hemolytically active monomers upon the cleavage between Lys(251)
      and Met(252) by trypsin.

PMID- 15489232
TI  - Insulin-degrading enzyme in brain microvessels: proteolysis of amyloid {beta}
      vasculotropic variants and reduced activity in cerebral amyloid angiopathy.
AB  - The accumulation of amyloid beta (Abeta) in the walls of small vessels in the
      cerebral cortex is associated with diseases characterized by dementia or stroke.
      These include Alzheimer's disease, Down syndrome, and sporadic and hereditary
      cerebral amyloid angiopathies (CAAs) related to mutations within the Abeta
      sequence. A higher tendency of Abeta to aggregate, a defective clearance to the
      systemic circulation, and insufficient proteolytic removal have been proposed as
      mechanisms that lead to Abeta accumulation in the brain. By using
      immunoprecipitation and mass spectrometry, we show that insulin-degrading enzyme
      (IDE) from isolated human brain microvessels was capable of degrading (125)I
      insulin and cleaved Abeta-(1-40) wild type and the genetic variants Abeta A21G
      (Flemish), Abeta E22Q (Dutch), and Abeta E22K (Italian) at the predicted sites.
      In microvessels from Alzheimer's disease cases with CAA, IDE protein levels
      showed a 44% increase as determined by sandwich enzyme-linked immunosorbent assay
      and Western blot. However, the activity of IDE upon radiolabeled insulin was
      significantly reduced in CAA as compared with age-matched controls. These results
      support the notion that a defect in Abeta proteolysis by IDE contributes to the
      accumulation of this peptide in the cortical microvasculature. Moreover they
      raise the possibility that IDE inhibition or inactivation is a pathogenic
      mechanism that may open novel strategies for the treatment of cerebrovascular
      Abeta amyloidoses.

PMID- 15489233
TI  - Low density lipoprotein receptor-related protein mediates endocytic clearance of
      pro-MMP-2.TIMP-2 complex through a thrombospondin-independent mechanism.
AB  - The low density lipoprotein receptor-related protein (LRP) mediates the endocytic
      clearance of various proteinases and proteinase.inhibitor complexes, including
      thrombospondin (TSP)-dependent endocytosis of matrix metalloproteinase (MMP)-2
      (or gelatinase A), a key effector of extracellular matrix remodeling and cancer
      progression. However, the zymogen of MMP-2 (pro-MMP-2) mostly occurs in tissues
      as a complex with the tissue inhibitor of MMPs (TIMP-2). Here we show that
      clearance of the pro-MMP-2.TIMP-2 complex is also mediated by LRP, because
      addition of receptor-associated protein (RAP), a natural LRP ligand antagonist,
      inhibited endocytosis and lysosomal degradation of (125)I-pro-MMP-2.TIMP-2. Both
      TIMP-2 and the pro-MMP-2 collagen-binding domain independently competed for
      endocytosis of (125)I-pro-MMP-2.TIMP-2 complex. Surface plasmon resonance studies
      indicated that pro-MMP-2, TIMP-2, and pro-MMP-2.TIMP-2 directly interact with LRP
      in the absence of TSP. LRP-mediated endocytic clearance of (125)I-pro-MMP-2 was
      inhibited by anti-TSP antibodies and accelerated upon complexing with TSP-1, but
      these treatments had no effect on (125)I-pro-MMP-2.TIMP-2 uptake. This implies
      that mechanisms of clearance by LRP of pro-MMP-2 and pro-MMP-2.TIMP-2 complex are
      different. Interestingly, RAP did not inhibit binding of (125)I-pro-MMP-2.TIMP-2
      to the cell surface. We conclude that clearance of pro-MMP-2.TIMP-2 complex is a
      TSP-independent two-step process, involving (i) initial binding to the cell
      membrane in a RAP-insensitive manner and (ii) subsequent LRP-dependent (RAP
      sensitive) internalization and degradation.

PMID- 15489234
TI  - Synergistic activation of interleukin-12 p35 gene transcription by interferon
      regulatory factor-1 and interferon consensus sequence-binding protein.
AB  - Interferon regulatory factor-1 (IRF-1) and interferon consensus sequence-binding
      protein (ICSBP or IRF-8) are two members of the IRF family of transcription
      factors that play critical roles in interferon signaling in a wide range of host
      responses to infection and malignancy. Interleukin-12 (IL-12) is a key factor in
      the induction of innate resistance and generation of T helper type 1 cells and
      cytotoxic T lymphocytes. In this work, we find that ICSBP-deficient macrophages
      are highly defective in the production of IL-12. The defect is also observed at
      the level of IL-12 p40 and p35 mRNA expression. Transcriptional analyses revealed
      that ICSBP is a potent activator of the IL-12 p35 gene. It acts through a site
      localized to -226 to -219, named ICSBP-response element (ICSBP-RE), in the human
      IL-12 p35 promoter through physical association with IRF-1 both in vitro and in
      vivo. Co-expression of ICSBP and IRF-1 synergistically stimulates the IL-12 p35
      promoter activity. Mutations at the ICSBP-RE results in the loss of protein
      binding as well as transcriptional activation by ICSBP alone or together with IRF
      1. This study provides novel mechanistic information on how signals initiated
      during innate and adaptive immune responses synergize to yield greater IL-12
      production and sustained cellular immunity.

PMID- 15489236
TI  - pH-dependent Interactions of the carboxyl-terminal helix of steroidogenic acute
      regulatory protein with synthetic membranes.
AB  - Steroidogenic acute regulatory (StAR) protein facilitates import of cholesterol
      into adrenal and gonadal mitochondria where cholesterol is converted to
      pregnenolone, initiating steroidogenesis. StAR acts exclusively on the outer
      mitochondrial membrane (OMM) by unknown mechanisms. To identify StAR domains
      involved in membrane association, we reacted N-62 StAR with small unilamellar
      vesicles (SUVs) composed of lipids resembling the OMM. Solvent-exposed domains
      were digested with trypsin, Asp-N, or pepsin at different pH levels, and StAR
      peptides protected from proteolysis were identified by mass spectrometry. At pH 4
      SUVs completely protected residues 259-282; at pH 6.5 this region was partially
      digested into 254-272, 254-273, and 254-274. Computer-graphic modeling of N-62
      StAR indicated these peptides correspond to the C-terminal alpha4 helix and that
      residues Leu(275), Thr(263), and Arg(272) in alpha4 form stabilizing interactions
      with Gln(128), Asp(150), and Asp(106) in adjacent loops. CD spectroscopy of a 37
      mer model of alpha4 (residues 247-287) indicated a random coil in aqueous buffer,
      but in 40% methanol the peptide was alpha-helical and achieved maximal alpha
      helicity at pH 5.0 in the presence of SUVs. Reacting the 37-mer with diethyl
      pyrocarbamate incorporated into SUVs increased the number of modified residues.
      Thus the C-terminal alpha4 helix is critically involved in the membrane
      association of StAR with OMM lipids. The membrane association and the alpha
      helical structure of the C terminus in the presence of OMM lipids are also pH
      dependent. These results further support StAR undergoing a pH-dependent change in
      its conformation when interacting with the acidic phospholipid head groups of a
      membrane.

PMID- 15489235
TI  - Periplasmic cleavage and modification of the 1-phosphate group of Helicobacter
      pylori lipid A.
AB  - Pathogenic bacteria modify the lipid A portion of their lipopolysaccharide to
      help evade the host innate immune response. Modification of the negatively
      charged phosphate groups of lipid A aids in resistance to cationic antimicrobial
      peptides targeting the bacterial cell surface. The lipid A of Helicobacter pylori
      contains a phosphoethanolamine (pEtN) unit directly linked to the 1-position of
      the disaccharide backbone. This is in contrast to the pEtN units found in other
      pathogenic Gram-negative bacteria, which are attached to the lipid A phosphate
      group to form a pyrophosphate linkage. This study describes two enzymes involved
      in the periplasmic modification of the 1-phosphate group of H. pylori lipid A. By
      using an in vitro assay system, we demonstrate the presence of lipid A 1
      phosphatase activity in membranes of H. pylori. In an attempt to identify genes
      encoding possible lipid A phosphatases, we cloned four putative orthologs of
      Escherichia coli pgpB, the phosphatidylglycerol-phosphate phosphatase, from H.
      pylori 26695. One of these orthologs, Hp0021, is the structural gene for the
      lipid A 1-phosphatase and is required for removal of the 1-phosphate group from
      mature lipid A in an in vitro assay system. Heterologous expression of Hp0021 in
      E. coli resulted in the highly selective removal of the 1-phosphate group from E.
      coli lipid A, as demonstrated by mass spectrometry. We also identified the
      structural gene for the H. pylori lipid A pEtN transferase (Hp0022). Mass
      spectrometric analysis of the lipid A isolated from E. coli expressing Hp0021 and
      Hp0022 shows the addition of a single pEtN group at the 1-position, confirming
      that Hp0022 is responsible for the addition of a pEtN unit at the 1-position in
      H. pylori lipid A. In summary, we demonstrate that modification of the 1
      phosphate group of H. pylori lipid A requires two enzymatic steps.

PMID- 15489237
TI  - Molecular determinants in TRPV5 channel assembly.
AB  - The epithelial Ca(2+) channels TRPV5 and TRPV6 mediate the Ca(2+) influx in 1,25
      dihydroxyvitamin D(3)-responsive epithelia and are therefore essential in the
      maintenance of the body Ca(2+) balance. These Ca(2+) channels assemble in
      (hetero)tetrameric channel complexes with different functional characteristics
      regarding Ca(2+)-dependent inactivation, ion selectivity, and pharmacological
      block. Glutathione S-transferase pull-downs and co-immunoprecipitations
      demonstrated an essential role of the intracellular N- and C-tails in TRPV5
      channel assembly by physical interactions between N-N tails, C-C tails, and N-C
      tails. Patch clamp analysis in human embryonic kidney (HEK293) cells and
      (45)Ca(2+) uptake experiments in Xenopus laevis oocytes co-expressing TRPV5 wild
      type and truncated proteins indicated that TRPV5 Delta N (deleted N-tail) and
      TRPV5 Delta C (deleted C-tail) decreased channel activity of wild-type TRPV5 in a
      dominant-negative manner, whereas TRPV5 Delta N Delta C (deleted N-tail/C-tail)
      did not affect TRPV5 activity. Oocytes co-expressing wild-type TRPV5 and TRPV5
      Delta N or TRPV5 Delta C showed virtually no wild-type TRPV5 expression on the
      plasma membrane, whereas co-expression of wild-type TRPV5 and TRPV5 Delta N Delta
      C displayed normal channel surface expression. This indicates that TRPV5
      trafficking toward the plasma membrane was disturbed by assembly with TRPV5 Delta
      N or TRPV5 Delta C but not with TRPV5 Delta N Delta C. TRPV5 channel assembly
      signals were refined between amino acid positions 64-77 and 596-601 in the N-tail
      and C-tail, respectively. Pull-down assays and co-immunoprecipitations
      demonstrated that N- or C-tail mutants lacking these critical assembly domains
      were unable to interact with tails of TRPV5. In conclusion, two domains in the N
      tail (residues 64-77) and C-tail (residues 596-601) of TRPV5 are important for
      channel subunit assembly, subsequent trafficking of the TRPV5 channel complex to
      the plasma membrane, and channel activity.

PMID- 15489238
TI  - Falling estradiol levels as a result of intentional reduction in gonadotrophin
      dose are not associated with poor IVF outcomes, whereas spontaneously falling
      estradiol levels result in low clinical pregnancy rates.
AB  - BACKGROUND: Although estradiol levels remain an integral part of monitoring in
      most IVF programmes, the effect of falling estradiol on IVF outcome has not been
      adequately quantified. The objective of this study was to evaluate the effect of
      falling estradiol levels prior to hCG on IVF outcome. METHODS: This was a
      retrospective cohort study carried out in a university-based fertility clinic. A
      total of 112 IVF patients in whom estradiol levels fell prior to the
      administration of hCG were matched for age and year of treatment with 112 control
      IVF patients. IVF outcomes including oocytes retrieved, fertilization rate,
      embryos for transfer, and pregnancy rates were compared between the groups.
      RESULTS: Seventy per cent of women in the falling estradiol group experienced
      spontaneously falling estradiol levels. Spontaneously falling estradiol was
      associated with fewer oocytes retrieved (median 5 versus 8, P=0.001), increased
      rates of failed fertilization (18 versus 6%, P=0.018) and lower clinical
      pregnancy rates (12 versus 26%, P=0.012) compared to controls. Despite marked
      decreases in estradiol levels, IVF outcomes for patients whose estradiol levels
      fell as a result of deliberate protocol modification had similar fertilization
      and clinical pregnancy rates as controls. CONCLUSIONS: Subtle (<10%) spontaneous
      decreases in estradiol levels are associated with very poor IVF outcomes.

PMID- 15489239
TI  - Research hurdles complicating the analysis of infertility treatment and child
      health.
AB  - Research aimed at the empirical evaluation of infertility treatment including
      assisted reproductive technologies (ART) on child health and development is
      hampered by investigators' inability to methodologically separate possible
      treatment effects from underlying fecundity impairments. While the literature
      continues to identify ART as a risk factor for many child health outcomes, less
      attention has been paid to the methodologic rigor needed to answer this question.
      We identify aspects of fecundity and the nuances of medical practice that need to
      be considered and captured when designing epidemiologic investigations aimed at
      assessing ART and child health. These include: (i) the use of prospective study
      designs in which the unit of analysis (cycle versus individual versus couple) is
      defined; (ii) data collection on relevant time-varying covariates at, before and
      during treatment; and (iii) the use of statistical techniques appropriate for
      hierarchical data and correlated exposures. While none of these issues in and by
      itself is unique to ART research, attention to these issues has been lacking in
      much of the published research limiting our ability to evaluate health
      consequences for children. Longitudinal studies of children conceived with ART
      will benefit from attention to these issues and, hopefully, produce answers to
      lingering questions about safety.

PMID- 15489240
TI  - Ethics of testicular stem cell medicine.
AB  - The ethical issues raised by advances in reproductive technology allowing the
      transplantation of testicular stem cells to enable infertile men and cancer
      patients, including the pre-pubertal, to have children, and to provide new
      contraceptive prospects for fertile men are discussed. Consideration of respect
      for the patient's autonomy, the need for informed consent and the health of any
      offspring resulting from such a procedure are included. Topics covered include:
      the problems raised by cases needing consent for the transplantation of
      testicular stem cells from pre-pubertal and adolescent patients; the legal status
      of stem cells; the arguements for treating such tissue as property which might
      serve as a means of guaranteeing respect for patients' rights in disputed cases;
      aspects of patents and the ethics of allowing commercial traffic of such
      material; questions relating to health and safety, as well as xenotransplantation
      technology in humans; and posthumous procurement use of germ cells from minors.
      Proposals are made to enhance informed and effective consent, while supporting
      patient determination, choice, autonomy and technological advances. The paper
      appeals to the emerging EU directives in relation to tissue procurement, storing
      and use of tissue and cells to adopt a pragmatic and meaningful position which
      will help enhance patient determination and autonomy in relation to the emerging
      technologies in reproductive medicine, whilst providing a pragmatic way forward
      for fertility clinics and laboratories to function.

PMID- 15489241
TI  - Cyclooxygenase-2-derived endogenous prostacyclin enhances mouse embryo hatching.
AB  - INTRODUCTION: The role of prostaglandins (PGs) in embryo hatching remains
      controversial. In addition, there is no direct evidence that mouse embryos
      synthesize PGs. METHODS: The effects of endogenous PG on mouse embryo hatching
      were evaluated by blocking endogenous PG synthesis with indomethacin. Specific
      cyclooxygenase (COX) inhibitors were used to identify the role of COX-1- and COX
      2-derived PGs. An eicosanoid profile was generated by incubating blastocysts with
      [3H]arachidonic acid and analysing the metabolites by high performance liquid
      chromatography. The expression and the localization of COX-1, COX-2 and
      prostacyclin synthase (PGIS) were examined by western blot analysis and
      immunohistochemistry. RESULTS: The hatching of embryos cultured in 30 microl of
      protein-free medium was blocked by indomethacin (P = 0.007) or a selective COX-2
      inhibitor (P = 0.004). Adding back iloprost, a prostacyclin analogue, abolished
      the effects of the COX-2 inhibitor. Prostacyclin was the most abundant PG
      produced by mouse blastocysts, which expressed COX-1, COX-2 and PGIS. COX-1, COX
      2 and PGIS were expressed in 4-cell stage embryos and beyond; they were present
      in the inner cell mass and the trophectoderm of the blastocysts. CONCLUSION:
      Mouse embryos express COX-1, COX-2 and PGIS which catalyse the formation of PGI2;
      COX-2-derived PGI2 plays a critical role in embryo hatching.

PMID- 15489242
TI  - Transmission risk of hepatitis C virus via semen during assisted reproduction:
      how real is it?
AB  - The risk of viral transmissibility in assisted reproduction is still a much
      debated issue, especially for hepatitis C virus (HCV). HCV is a common causative
      agent for parenterally transmitted viral hepatitis. In addition, it has been
      incriminated in other routes of transmission, including sexual transmission and
      nosocomial infections. The management of infertility, in association with HCV,
      has sparked debates about the potential risk of spread of infection to virus-free
      individuals, embryos and/or semen. The lack of worldwide-accepted screening
      policies has helped to fuel this debate. Today, it is evident that there is a
      potential risk of spread of HCV through biological fluids, including semen, to
      other individuals. This risk can only be marginalized by the use of well
      established criteria for safety in infertility centres, and by the use of proper
      initial detection and segregation of potentially hazardous materials. Techniques
      and protocols have been established to help the andrologist and embryologist to
      safeguard patients against such dangers, and should be imposed in all centres,
      allowing HCV-positive males to enter their assisted reproduction programmes.

PMID- 15489243
TI  - Association between MSH4 (MutS homologue 4) and the DNA strand-exchange RAD51 and
      DMC1 proteins during mammalian meiosis.
AB  - During meiotic prophase, chromosomes must undergo highly regulated recombination
      events, some of which lead to reciprocal exchanges. In yeast, MSH4, a meiosis
      specific homologue of the bacterial MutS protein, is required for meiotic
      recombination. In mice, disruption of the Msh4 gene results in male and female
      infertility due to meiotic failure. To date, the implication of MSH4 mutations
      has not been established in human sterility. However, it is noteworthy that
      mutant mice exhibit a defect in the chromosome synapsis, strikingly similar to
      the clinical observations found in human infertility. As a step towards
      understanding the molecular mechanisms underlying the role of MSH4 in human
      gametogenesis, we decided to determine whether this protein interacts with
      recombination machinery enzymes. Our results provide biochemical evidence
      indicating that the human MSH4 protein physically interacts with both RAD51 and
      DMC1, two RecA homologues known to initiate DNA strand-exchange between
      homologous chromosomes. Immunolocalization analyses show that some MSH4 foci,
      located on mouse meiotic chromosomes, colocalize with DMC1/RAD51 complexes. Our
      data support the view that MSH4 is associated with the early meiotic
      recombination machinery in mammals. We consider the possibility that MSH4 is
      involved in the regulation of recombination events by exerting a function closely
      after DNA strand-exchange has been initiated.

PMID- 15489244
TI  - Surfactant protein D is present in the human female reproductive tract and
      inhibits Chlamydia trachomatis infection.
AB  - Surfactant protein D (SP-D) is a lung collectin involved in innate host defence
      mechanisms in the lung. SP-D is also expressed at other mucosal sites throughout
      the human body. In the present study, we show that SP-D mRNA and protein are
      expressed in the human female reproductive tract. SP-D protein was localized in
      the apical portion of the reproductive epithelial cells. We also demonstrate that
      endometrial and endocervical cell lines and primary endocervical cells in culture
      produce SP-D mRNA and protein. Chlamydia trachomatis is an intracellular pathogen
      that infects the female reproductive tract, primarily the cervix, and is
      responsible for the most prevalent infectious disease in the USA. Untreated
      chlamydial infections of the female reproductive tract often result in sterility
      of the infected woman. Since SP-D protein is produced in cervical glands, we
      examined the effect of SP-D on chlamydial infection of cervical epithelial cells
      in vitro. We found that SP-D protein inhibits the infection of HeLa cells (an
      endocervical epithelial cell line) by C. trachomatis in a dose-dependent manner.
      We further demonstrate that the SP-D lectin-binding domain is involved in
      inhibiting infection of HeLa cells by Chlamydia. In conclusion, we detected SP-D
      in the female reproductive tract and determined that one of the functions of the
      SP-D protein may be to protect cervical epithelial cells from infection by C.
      trachomatis.

PMID- 15489245
TI  - Mechanical stretch of human uterine smooth muscle cells increases IL-8 mRNA
      expression and peptide synthesis.
AB  - Labour is associated with increased synthesis of interleukin-8 (IL-8) by the
      fetal membranes and myometrium, which leads to an inflammatory infiltrate.
      Stretch has been shown to increase the expression of contraction-associated
      proteins in animal models of labour and in human myocytes in vitro. In this
      study, we tested the hypothesis that mechanical stretch of human myometrial cells
      increases IL-8 messenger ribonucleic acid (mRNA) expression. We isolated myocytes
      from non-pregnant women undergoing hysterectomy and pregnant women undergoing
      Caesarean section before and after the onset of labour. Myocytes in culture were
      subjected to stretch of varying intensity (6-16%) and duration (1 or 6 h) using
      the Flexercell system. IL-8 mRNA expression was lowest in myocytes from pregnant
      women not in labour, intermediate in those from non-pregnant women and greatest
      in those from pregnant women in labour. Stretch increased IL-8 mRNA expression
      independent of reproductive state. The stretch-induced increase in IL-8 mRNA
      expression was associated with higher IL-8 levels in the culture supernatant and
      enhanced promoter activity. These data suggest that stretch contributes to the
      increase in myometrial IL-8 synthesis associated with the onset of labour in
      humans.

PMID- 15489246
TI  - Bactericidal activity of amoxicillin against non-susceptible Streptococcus
      pneumoniae in an in vitro pharmacodynamic model simulating the concentrations
      obtained with the 2000/125 mg sustained-release co-amoxiclav formulation.
AB  - OBJECTIVES: To investigate the bactericidal activity against Streptococcus
      pneumoniae of simulated amoxicillin serum concentrations obtained in humans after
      2000/125 mg sustained-release (SR) and 875/125 mg co-amoxiclav administered twice
      and three times a day, respectively. METHODS: An in vitro computerized
      pharmacodynamic simulation was carried out and colony counts were determined over
      24 h. Ten strains non-susceptible to amoxicillin (four of them exhibiting an MIC
      of 4 mg/L, five strains with an MIC of 8 mg/L and one strain with an MIC of 16
      mg/L) were used. RESULTS: With amoxicillin 2000 mg, an initial inoculum reduction
      >99.99% was obtained for strains with an MIC of 4 mg/L, > or =99% for strains
      with an MIC of 8 mg/L and 70.6% for the strain with an MIC of 16 mg/L at 24 h
      sampling time. At this sampling time, no reduction of initial inocula was
      obtained with amoxicillin 875 mg/8 h for two of the four strains with an MIC of 4
      mg/L, three of the five strains with an MIC of 8 mg/L or for the strain with an
      MIC of 16 mg/L. CONCLUSIONS: The new co-amoxiclav 2000/125 mg SR formulation
      appears to offer advantages versus previous formulations with respect to
      bactericidal activity against current amoxicillin non-susceptible strains.

PMID- 15489247
TI  - Fluorescent dyes alter intracellular targeting and function of cell-penetrating
      tetrapeptides.
AB  - Fluorescent labels are commonly used to investigate the mechanisms of cellular
      uptake and intracellular distribution of cell-penetrating peptides. However,
      labels such as fluorescein and rhodamine are relatively large and very lipophilic
      and may significantly alter physicochemical properties of small peptides. To
      minimize the impact of the fluorescent probe on a tetrapeptide, we substituted
      one of the amino acids (Lys4) in a tetrapeptide ([Dmt1]DALDA, Dmt-D-Arg-Phe-Lys
      NH2 where Dmt = 2',6'-dimethyltyrosine) with two different fluorescent amino
      acids (beta-dansyl-L-alpha,beta-diaminopropionic acid (dnsDap4) or beta
      anthraniloyl-L-alpha,beta-diaminopropionic acid (atnDap4)). Initial studies with
      confocal laser scanning microscopy (CLSM) showed very different localization
      patterns for the two fluorescent analogs, with [Dmt1,atnDap4]DALDA showing
      mitochondrial localization and [Dmt1,dnsDap4]DALDA showing diffuse cytoplasmic
      localization. Studies with isolated mouse liver mitochondria suggested that
      [Dmt1,dnsDap4]DALDA targeted the mitochondrial matrix resulting in mitochondrial
      depolarization, opening of the permeability transition pore, mitochondrial
      swelling, and rapid release of the peptide into the cytoplasm. In contrast,
      [Dmt1,atnDap4]DALDA was retained in the inner mitochondrial membrane and did not
      induce mitochondrial swelling. Furthermore, [Dmt1,atnDap4]DALDA protected
      mitochondria against Ca2+-induced swelling. Importantly, the unlabeled parent
      peptide [Dmt1]DALDA behaved like [Dmt1,atnDap4]DALDA and was mitoprotective.
      These findings suggest that experimental results obtained with fluorescent labels
      must be interpreted with caution, and the use of multiple fluorophores, together
      with confirmation using the original or radiolabeled molecule, is recommended.

PMID- 15489248
TI  - Intracellular acidosis-activated p38 MAPK signaling and its essential role in
      cardiomyocyte hypoxic injury.
AB  - Activation of p38 mitogen-activated protein kinase (MAPK) plays a central role in
      cellular responses to a multitude of stress signals. In the heart, enhanced p38
      MAPK signaling has been implicated in cardiac hypoxic and ischemic injury.
      However, the mechanism underlying hypoxia-induced p38 MAPK activation remains
      elusive. We investigated p38 MAPK activation during hypoxia in adult rat
      cardiomyocytes. Here, we reported that hypoxia leads to concurrent intracellular
      acidosis and activation of p38 MAPK and that the hypoxia-induced p38 MAPK
      signaling can be fully abolished by neutralizing intracellular pH, whereas
      intracellular acidosis (intracellular pH<7.0) per se overtly augments activation
      of p38 MAPK but not ERK1/2 and JNK. Furthermore, inhibition of p38 MAPK protects
      myocytes against hypoxic cell death, suggesting that acidosis-evoked p38 MAPK
      signaling plays an important role in hypoxic cell injury and cell death. These
      results demonstrate, for the first time, that intracellular acidosis constitutes
      a necessary and sufficient link responsible for hypoxia-activated p38 MAPK
      signaling and the subsequent hypoxic cardiomyocyte injury and death.

PMID- 15489249
TI  - Activation of TRPC6 channel proteins: evidence for an essential role of
      phosphorylation.

PMID- 15489250
TI  - Persistent gamma oscillations in superficial layers of rat auditory neocortex:
      experiment and model.
AB  - Persistent in vitro gamma oscillations, induced by bath application of carbachol
      and kainate (amongst other drugs), were discovered by Eberhard Buhl and
      collaborators in 1998. The oscillations are robust, in that they can continue for
      hours; but the oscillations are also intricate in their mechanisms: they depend
      upon phasic synaptic excitation and inhibition, upon electrical coupling between
      interneurones and between pyramidal neurones, and--at least in neocortex--they
      depend upon complex intrinsic properties of some of the neurones.

PMID- 15489252
TI  - Breeding system in a population of Trigonella balansae (Leguminosae).
AB  - BACKGROUND AND AIMS: Although some taxonomic studies in the genus Trigonella have
      been conducted, there has been no concerted effort to study the breeding system.
      This paper examines the floral structure and pollination system in a population
      of T. balansae, an annual pasture legume. METHODS: Floral morphology, hand and
      vector pollination, stigma receptivity, pollen tube growth, using scanning
      electron and fluorescence microscopy, were conducted. KEY RESULTS: Measurements
      of floral structure from before to after anthesis indicates an inability for T.
      balansae to self-pollinate and a requirement for an external vector to
      effectively transfer pollen from the anthers onto the stigmas of this species.
      Seed set can be obtained by hand or honeybee manipulation of T. balansae flowers.
      CONCLUSIONS: Trigonella balansae is a self-compatible species, but which requires
      vectors such as honeybees to bring about pollination.

PMID- 15489251
TI  - Spontaneous low-frequency voltage oscillations in frog saccular hair cells.
AB  - Spontaneous membrane voltage oscillations were found in 27 of 130 isolated frog
      saccular hair cells. Voltage oscillations had a mean peak-to-peak amplitude of 23
      mV and a mean oscillatory frequency of 4.6 Hz. When compared with non-oscillatory
      cells, oscillatory cells had significantly greater hyperpolarization-activated
      and lower depolarization-activated current densities. Two components, the
      hyperpolarization-activated cation current, I(h), and the K(+)-selective inward
      rectifier current, I(K1), contributed to the hyperpolarization-activated current,
      as assessed by the use of the I(K1)-selective inhibitor Ba(2+) and the I(h)
      selective inhibitor ZD-7288. Five depolarization-activated currents were present
      in these cells (transient I(BK), sustained I(BK), I(DRK), I(A), and I(Ca)), and
      all were found to have significantly lower densities in oscillatory cells than in
      non-oscillatory cells (revealed by using TEA to block I(BK), 4-AP to block
      I(DRK), and prepulses at different voltages to isolate I(A)). Bath application of
      either Ba(2+) or ZD-7288 suppressed spontaneous voltage oscillations, indicating
      that I(h) and I(K1) are required for generating this activity. On the contrary,
      TEA or Cd(2+) did not inhibit this activity, suggesting that I(BK) and I(Ca) do
      not contribute. A mathematical model has been developed to test the
      interpretation derived from the pharmacological and biophysical data. This model
      indicates that spontaneous voltage oscillations can be generated when the
      electrophysiological features of oscillatory cells are used. The oscillatory
      behaviour is principally driven by the activity of I(K1) and I(h), with I(A)
      playing a modulatory role. In addition, the model indicates that the high
      densities of depolarization-activated currents expressed by non-oscillatory cells
      help to stabilize the resting membrane potential, thus preventing the spontaneous
      oscillations.

PMID- 15489254
TI  - Rapid natriuretic action of aldosterone in the rat.
AB  - Rapid, nongenomic actions of aldosterone have been demonstrated in a number of
      cell types in vitro, including renal cell lines, but there remains little direct
      evidence that it is able to exert rapid effects on the kidney in the whole
      animal. Accordingly, the aim of this study was to determine whether aldosterone
      induces rapid changes in the renal handling of electrolytes or acid-base balance
      in the anesthetized rat. With the use of a servo-controlled fluid replacement
      system, spontaneous urine output by anesthetized male Sprague-Dawley rats was
      replaced with 2.5% dextrose. After a 3-h equilibration and a 1-h control period,
      rats were infused with aldosterone (42 pmol/min) or vehicle for 1 h. Aldosterone
      infusion induced a rapid (within 15 min) increase in sodium excretion that peaked
      at 0.24 +/- 0.08 compared with 0.04 +/- 0.01 micromol x min(-1) 100 x body
      weight(-1) (P = 0.041) in the vehicle-infused rats. This natriuresis was not
      associated with changes in glomerular filtration rate; urine flow rate;
      potassium, chloride, or bicarbonate excretion; or urine pH. The mechanisms
      involved are unclear, but because we have previously shown that aldosterone
      stimulates a rapid (4 min) increase in cAMP generation in the rat inner medullary
      collecting duct (IMCD) (Sheader EA, Wargent ET, Ashton N, and Balment RJ. J
      Endocrinol 175: 343-347, 2002), they could involve cAMP-mediated activation of
      the cystic fibrosis transmembrane conductance regulator chloride channel, which
      drives sodium secretion in the IMCD.

PMID- 15489253
TI  - Natural hybridization between a deciduous (Nothofagus antarctica, Nothofagaceae)
      and an evergreen (N. dombeyi) forest tree species: evidence from morphological
      and isoenzymatic traits.
AB  - BACKGROUND AND AIMS: Trees with a partial leaf-shedding pattern and other
      morphological features a priori considered intermediate between those of the
      deciduous Nothofagus antarctica (G. Forster) Oersted and the evergreen N. dombeyi
      (Mirb.) Oersted (Nothofagaceae) were found in natural stands. The hybridization
      between a deciduous and an evergreen species of Nothofagus has not been reported
      so far in natural communities. METHODS: The putative hybrids and the two presumed
      parental species were compared using 14 enzyme systems as well as shoot, leaf and
      reproductive morphology. KEY RESULTS: Six enzyme systems showed good resolution
      (MDH-B, IDH, SKDH, 6-PGDH, GOT and PGI) and in four of them (PGI, MDH-B, SKDH and
      6-PGDH) the putative hybrids showed intermediate zymogram patterns between N.
      antarctica and N. dombeyi. Both principal coordinates analysis on isozyme data
      and principal components analysis (PCA) on quantitative morphological traits of
      shoots and leaves separated both parental species and located the putative
      hybrids closer to N. antarctica than to N. dombeyi. In the PCA, the number of
      basal cataphylls and the length : width ratio of leaves were the variables most
      discriminating among shoots of the three entities. The putative hybrids were
      intermediate between both species regarding leaf vernation, outline and venation,
      variation in leaf shape (length/width) with position on the parent shoot and in
      staminate inflorescence and cupule morphology. For other morphological traits,
      the putative hybrids resembled one of the parental species or differed from both
      species (e.g. valve morphology). CONCLUSIONS: Isoenzymatic and morphological data
      sets support the idea of the hybrid nature (probably F1 generation) of the semi
      deciduous trees found. Nothofagus antarctica and N. dombeyi are probably more
      closely related than previously assumed. The relevance of pollen type in
      revealing evolutionary relationships between Nothofagus species is supported, and
      that of leaf-shedding pattern is rejected.

PMID- 15489255
TI  - Putative protective effect of inspiratory threshold loading against exercise
      induced supraspinal diaphragm fatigue.
AB  - The present investigation was intended to assess the consequences of an
      inspiratory load on the diaphragm central component of fatigue during exercise.
      We recorded the motor potential evoked (MEP) by transcranial magnetic stimulation
      of the motor cortex in 10 subjects. The diaphragm and rectus femoris were studied
      before and 10, 20, and 40 min after two 16-min cycling exercise (E) trials
      requiring 55% of maximal oxygen uptake: 1) one with an inspiratory threshold load
      (E + ITL), corresponding to 10% of maximal inspiratory pressure; and 2) the other
      without the load (E). Dyspnea, heart rate, electromyographic activity of the
      sternocleidomastoid, and diaphragm work were significantly higher in E + ITL than
      in E. Neither trial affected the response to phrenic magnetic stimulation, which
      was performed 15 and 25 min postexercise, or the maximal inspiratory pressure
      (116 and 120 cm H(2)O before E and E + ITL, respectively, and 110 and 114 cm
      H(2)O at 30 min postexercise). Whereas the amplitude of the diaphragm MEP was
      unaffected by E + ITL (+2.1 +/- 29.4%), a significant decrease was observed 10
      min after E compared with baseline (-37.1 +/- 22.3%) and compared with E + ITL.
      The MEP amplitude of rectus femoris remained unchanged with E and E + ITL. The
      recruitment of synergistic agonists during E + ITL may have normalized the major
      ventilatory stress and reset up the excitability of the diaphragm pathway.

PMID- 15489256
TI  - Neck muscle fatigue and spatial orientation during stepping in place in humans.
AB  - Neck proprioceptive input, as elicited by muscle vibration, can produce
      destabilizing effects on stance and locomotion. Neck muscle fatigue produces
      destabilizing effects on stance, too. Our aim was to assess whether neck muscle
      fatigue can also perturb the orientation in space during a walking task.
      Direction and amplitude of the path covered during stepping in place were
      measured in 10 blindfolded subjects, who performed five 30-s stepping trials
      before and after a 5-min period of isometric dorsal neck muscle contraction
      against a load. Neck muscle electromyogram amplitude and median frequency during
      the head extensor effort were used to compute a fatigue index. Head and body
      kinematics were recorded by an optoelectronic system, and stepping cadence was
      measured by sensorized insoles. Before the contraction period, subjects normally
      stepped on the spot or drifted forward. After contraction, some subjects
      reproduced the same behavior, whereas others reduced their forward progression or
      even stepped backward. The former subjects showed minimal signs of fatigue and
      the latter ones marked signs of fatigue, as quantified by the dorsal neck
      electromyogram index. Head position and cadence were unaffected in either group
      of subjects. We argue that the abnormal fatigue-induced afferent input
      originating in the receptors transducing the neck muscle metabolic state can
      modulate the egocentric spatial reference frame. Notably, the effects of neck
      muscle fatigue on orientation are opposite to those produced by neck
      proprioception. The neck represents a complex source of inputs capable of
      modifying our orientation in space during a locomotor task.

PMID- 15489257
TI  - Pulmonary artery smooth muscle activation attenuates arterial dysfunction during
      acute pulmonary hypertension.
AB  - Acute pulmonary hypertension (PH) may arise with or without an increase in
      vascular smooth muscle (VSM) tone. Our objective was to determine how VSM
      activation affects both the conduit (CF) and wall buffering (BF) functions of the
      pulmonary artery (PA) during acute PH states. PA instantaneous flow, pressure,
      and diameter of six sheep were recorded during normal pressure (CTL) and
      different states of acute PH: 1) passively induced by PA mechanical occlusion
      (PPH); 2) actively induced by intravenous administration of phenylephrine (APH);
      and 3) a combination of both (APPH). To evaluate the direct effect of VSM
      activation, isobaric (PPH vs. APH) and isometric (CTL vs. APPH) analyses were
      performed. We calculated the local BF from the elastic (EPD) and viscous (etaPD)
      indexes as etaPD/EPD and the characteristic impedance (ZC) from pressure and flow
      to evaluate CF as 1/ZC. We also calculated the absolute and normalized cross
      sectional pulsatility (PCS and NPCS, respectively), the dynamic compliance
      (CDYN), the cross-sectional distensibility (DCS), and the pressure-strain elastic
      modulus (EP). The isobaric analysis showed increase of CF, BF, and etaPD (P <
      0.01) and decrease of EPD (P < 0.05) during APH in respect to PPH (concomitant
      with isobaric VSM activation-induced vasoconstriction, P < 0.01). The isometric
      analysis showed increase of E(PD) and etaPD (P < 0.01), nonsignificant difference
      in BF (even in the presence of a significant mean PA pressure rise, from 14 (SD
      6) to 25 (SD 8) mmHg, P < 0.01), and decrease in CF (P < 0.01) during APPH
      respect to CTL. Mechanical occlusions (PPH and APPH) reduced BF (P < 0.01) and
      increased EPD (P < 0.05) with regard to their previous steady states (CTL and
      APH). Nonsignificant differences were found in EPD between PPH and APPH. VSM
      activation (APH and APPH) increased etaPD (P < 0.01) respect to their previous
      passive states (CTL and PPH), but no significant differences were found within
      similar levels of VSM activation. In conclusion, VSM plays a relevant role in
      main pulmonary artery function during acute pulmonary hypertension, because
      isobaric vasoconstriction induced by VSM activation improves both BF and CF,
      mainly due to the increase in etaPD concomitant with the arterial compliance.
      CDYN and DCS were the more pertinent clinical indexes of arterial elasticity.
      Additionally, the etaPD-mediated preservation of the BF could be evaluated by the
      geometric related indexes (PCS and NPCS), which appear to be qualitative markers
      of arterial wall viscosity status.

PMID- 15489258
TI  - Active cutaneous vasodilation in resting humans during mild heat stress.
AB  - The role of skin temperature in reflex control of the active cutaneous
      vasodilator system was examined in six subjects during mild graded heat stress
      imposed by perfusing water at 34, 36, 38, and 40 degrees C through a tube-lined
      garment. Skin sympathetic nerve activity (SSNA) was recorded from the peroneal
      nerve with microneurography. While monitoring esophageal, mean skin, and local
      skin temperatures, we recorded skin blood flow at bretylium-treated and untreated
      skin sites by using laser-Doppler velocimetry and local sweat rate by using
      capacitance hygrometry on the dorsal foot. Cutaneous vascular conductance (CVC)
      was calculated by dividing skin blood flow by mean arterial pressure. Mild heat
      stress increased mean skin temperature by 0.2 or 0.3 degrees C every stage, but
      esophageal and local skin temperature did not change during the first three
      stages. CVC at the bretylium tosylate-treated site (CVC(BT)) and sweat expulsion
      number increased at 38 and 40 degrees C compared with 34 degrees C (P < 0.05);
      however, CVC at the untreated site did not change. SSNA increased at 40 degrees C
      (P < 0.05, different from 34 degrees C). However, SSNA burst amplitude increased
      (P < 0.05), whereas SSNA burst duration decreased (P < 0.05), at the same time as
      we observed the increase in CVC(BT) and sweat expulsion number. These data
      support the hypothesis that the active vasodilator system is activated by changes
      in mean skin temperature, even at normal core temperature, and illustrate the
      intricate competition between active vasodilator and the vasoconstrictor system
      for control of skin blood flow during mild heat stress.

PMID- 15489259
TI  - Effects of relaxin on systemic arterial hemodynamics and mechanical properties in
      conscious rats: sex dependency and dose response.
AB  - We previously showed that chronic administration of recombinant human relaxin
      (rhRLX; 4 microg/h) to conscious female, nonpregnant rats to reach serum levels
      corresponding to early to midgestation (approximately 20 ng/ml) increases cardiac
      output (CO) and global arterial compliance (AC) and decreases systemic vascular
      resistance (SVR), comparable to changes observed in midterm pregnancy. The goals
      of this study were to test whether chronic administration of rhRLX (4 microg/h)
      to conscious male rats will yield similar changes in CO and systemic arterial
      load and to determine whether higher infusion rates of rhRLX (50 microg/h)
      administered to nonpregnant female rats yielding serum concentrations
      corresponding to late pregnancy ( approximately 80 ng/ml) will further modify CO
      and SVR and global AC comparable to late gestation. CO and systemic arterial
      load, as quantified by SVR and AC, were obtained by using the same methods as in
      our previous studies. With respect to baseline, chronic rhRLX administration to
      male rats over 10 days at 4 mug/h increased both CO (20.5 +/- 4.2%) and AC (19.4
      +/- 6.9%) and reduced SVR (12.7 +/- 3.9%). These results were comparable to those
      elicited by the hormone in nonpregnant female rats. In contrast, neither acute
      (over 4 h) nor chronic (over 6 days) infusion of the higher dose of rhRLX
      administered to conscious female rats resulted in significant changes in CO, AC,
      or SVR from baseline. We conclude that 1) rhRLX increases CO and AC and reduces
      SVR irrespective of sex, and 2) the rhRLX dose response is biphasic insofar as
      significant alterations in CO and systemic arterial load fail to occur at high
      serum concentrations.

PMID- 15489260
TI  - Sympathetic neural regulation in endurance-trained humans: fitness vs. fatness.
AB  - We tested the hypothesis that muscle sympathetic nerve activity (MSNA) would be
      higher in endurance-trained (ET) compared with sedentary (Sed) men with similar
      levels of total body and abdominal adiposity. We further hypothesized that
      sympathetic baroreflex gain would be augmented in ET compared with Sed men
      independent of the level of adiposity. To address this, we measured MSNA (via
      microneurography), sympathetic and vagal baroreflex responses (the modified
      Oxford technique), body composition (dual-energy X-ray absorptiometry), and waist
      circumference (Gulick tape) in Sed (n = 22) and ET men (n = 8). The ET men were
      also compared with a subgroup of Sed men (n = 6) with similar levels of total
      body and abdominal adiposity. Basal MSNA was greater in the ET compared with Sed
      men with similar levels of total body and abdominal adiposity (28 +/- 2.0 vs. 21
      +/- 2.0 bursts/min; P < 0.05) but similar to the larger group of Sed men (n = 22)
      with higher total body and abdominal adiposity (vs. 26 +/- 3 bursts/min; P >
      0.05). In contrast to our hypothesis, sympathetic baroreflex gain was lower in
      the ET compared with Sed men (-6.4 +/- 0.8 vs. -8.4 +/- 0.4 arbitrary integrative
      units x beat(-1) x mmHg(-1); P < 0.05) regardless of the level of adiposity.
      Taken together, the results of the present study suggest that MSNA is higher in
      ET compared with Sed men with similar levels of total body and abdominal
      adiposity. In addition, sympathetic baroreflex gain is lower in ET compared with
      Sed men. That sympathetic baroreflex gain was lower in ET compared with Sed men
      regardless of the level of adiposity suggests an influence of the ET state per
      se.

PMID- 15489261
TI  - Resuscitation with lactated Ringer solution limits the expression of molecular
      events associated with lung injury after hemorrhage.
AB  - The aim of this study was to determine whether hemorrhage altered the caspase-3
      activity and the ATP levels in rat lung and ileum tissues and determine whether
      resuscitation with lactated Ringer solution (LR) or whole blood (WB) reversed
      these changes. Male Sprague-Dawley rats were briefly anesthetized with
      isoflurane, and their mean arterial blood pressure was reduced from 110 to 40
      mmHg by bleeding. The bled rat was then resuscitated with LR or autologous WB to
      bring mean arterial blood pressure back to 80 mmHg. Lung and ileum tissues were
      removed at the end of hemorrhage or at the end of the resuscitation period for
      specified bioassays. Hemorrhage increased cellular caspase-3 activity in the lung
      and the ileum. After the hemorrhaged rats received LR or WB, caspase-3 activity
      returned to the basal level in the lung and ileum, respectively. Likewise,
      hemorrhage decreased cellular ATP levels in lung and ileum. After LR or WB
      resuscitation, the cellular ATP level returned to the basal level only in the
      lung resuscitated with LR. The increased caspase-3 activity was associated with
      the increased expression of caspase-3 mRNA, which also returned to normal levels
      after either resuscitation. Similarly, hemorrhage increased the expression of
      inducible nitric oxide synthase and Kruppel-like factor 6 and decreased
      expression of Kruppel-like factor 4. Subsequent LR resuscitation normalized the
      expression of these genes in the lung tissue. Our results demonstrate that
      resuscitation with LR can reverse the expression of genes and their products that
      are thought to contribute to hemorrhage-induced lung injury.

PMID- 15489262
TI  - Muscle activation and blood flow do not explain the muscle length-dependent
      variation in quadriceps isometric endurance.
AB  - We investigated the role of central activation in muscle length-dependent
      endurance. Central activation ratio (CAR) and rectified surface electromyogram
      (EMG) were studied during fatigue of isometric contractions of the knee extensors
      at 30 and 90 degrees knee angles (full extension = 0 degree). Subjects (n = 8)
      were tested on a custom-built ergometer. Maximal voluntary isometric knee
      extension with supramaximal superimposed burst stimulation (three 100-mus pulses;
      300 Hz) was performed to assess CAR and maximal torque capacity (MTC). Surface
      EMG signals were obtained from vastus lateralis and rectus femoris muscles. At
      each angle, intermittent (15 s on 6 s off) isometric exercise at 50% MTC with
      superimposed stimulation was performed to exhaustion. During the fatigue task, a
      sphygmomanometer cuff around the upper thigh ensured full occlusion (400 mmHg) of
      the blood supply to the knee extensors. At least 2 days separated fatigue tests.
      MTC was not different between knee angles (30 degrees : 229.6 +/- 39.3 N.m vs. 90
      degrees: 215.7 +/- 13.2 N.m). Endurance times, however, were significantly longer
      (P < 0.05) at 30 vs. 90 degrees (87.8 +/- 18.7 vs. 54.9 +/- 12.1 s, respectively)
      despite the CAR not differing between angles at torque failure (30 degrees: 0.95
      +/- 0.05 vs. 90 degrees: 0.96 +/- 0.03) and full occlusion of blood supply to the
      knee extensors. Furthermore, rectified surface EMG values of the vastus lateralis
      (normalized to prefatigue maximum) were also similar at torque failure (30
      degrees : 56.5 +/- 12.5% vs. 90 degrees : 58.3 +/- 15.2%), whereas rectus femoris
      EMG activity was lower at 30 degrees (44.3 +/- 12.4%) vs. 90 degrees (69.5 +/-
      25.3%). We conclude that differences in endurance at different knee angles do not
      find their origin in differences in central activation and blood flow but may be
      a consequence of muscle length-related differences in metabolic cost.

PMID- 15489263
TI  - Imp3p and Imp4p mediate formation of essential U3-precursor rRNA (pre-rRNA)
      duplexes, possibly to recruit the small subunit processome to the pre-rRNA.
AB  - In eukaryotes, formation of short duplexes between the U3 small nucleolar RNA
      (snoRNA) and the precursor rRNA (pre-rRNA) at multiple sites is a prerequisite
      for three endonucleolytic cleavages that initiate small subunit biogenesis by
      releasing the 18S rRNA precursor from the pre-rRNA. The most likely role of these
      RNA duplexes is to guide the U3 snoRNA and its associated proteins, designated
      the small subunit processome, to the target cleavage sites on the pre-rRNA.
      Studies by others in Saccharomyces cerevisiae have identified the proteins
      Mpp10p, Imp3p, and Imp4p as candidates to mediate U3-pre-rRNA interactions. We
      report here that Imp3p and Imp4p appear to stabilize an otherwise unstable duplex
      between the U3 snoRNA hinge region and complementary bases in the external
      transcribed spacer of the pre-rRNA. In addition, Imp4p, but not Imp3p, seems to
      rearrange the U3 box A stem structure to expose the site that base-pairs with the
      5' end of the 18S rRNA, thereby mediating duplex formation at a second site. By
      mediating formation of both essential U3-pre-rRNA duplexes, Imp3p and Imp4p may
      help the small subunit processome to dock onto the pre-rRNA, an event
      indispensable for ribosome biogenesis and hence for cell growth.

PMID- 15489264
TI  - Translationally controlled tumor protein is a target of tumor reversion.
AB  - By analyzing the gene expression profile between tumor cells and revertant
      counterparts that have a suppressed malignant phenotype, we previously reported a
      significant down-regulation of translationally controlled tumor protein (TCTP) in
      the revertants. In the present study, we derived, by using the H1 parvovirus as a
      selective agent, revertants from three major solid cancers: colon, lung, and
      melanoma cell lines. These cells have a strongly suppressed malignant phenotype
      both in vitro and in vivo. The level of TCTP is decreased in most of the
      revertants. To verify whether inhibition of TCTP expression induces changes in
      the malignant phenotype, in the classical, well established model of "flat
      reversion," v-src-transformed NIH3T3 cells were transfected with antisense TCTP.
      By inhibiting the expression of TCTP, the number of revertant cells was raised to
      30%, instead of the reported rate for spontaneous flat revertants of 10(-6).
      Because TCTP encodes for a histamine-releasing factor, we tested the hypothesis
      that inhibitors of the histaminic pathway could be effective against tumor cells.
      We show that some antihistaminic compounds (hydroxyzine and promethazine) and
      other pharmacological compounds with a related structure (including thioridazine
      and sertraline) kill tumor cells and significantly decrease the level of TCTP.
      All together, these data suggest that, with tumor reversion used as a working
      model, TCTP was identified as a target and drugs were selected that decrease its
      expression and kill tumor cells.

PMID- 15489265
TI  - Pleiotropic effects of the 8.1 HLA haplotype in patients with autoimmune
      myasthenia gravis and thymus hyperplasia.
AB  - The 8.1 haplotype of the HLA complex has been reproducibly associated with
      several autoimmune diseases and traits, notably with thymus hyperplasia in
      patients with acquired generalized myasthenia gravis, an autoantibody-mediated
      disease directed at the muscle acetylcholine receptor. However, the strong
      linkage disequilibrium across this haplotype has prevented the identification of
      the causative locus, termed MYAS1. Here, we localized MYAS1 to a 1.2-Mb genome
      segment by reconstructing haplotypes and assessing their transmission in 73
      simplex families. This segment encompasses the class III and proximal class I
      regions, between the BAT3 and C3-2-11 markers, therefore unambiguously excluding
      the class II loci. In addition, a case-control study revealed a very strong
      association with a core haplotype in this same region following an additive model
      (P=7 x 10(-11), odds ratio 6.5 for one copy and 42 for two copies of the core
      haplotype). Finally, we showed that this region is associated with a marked
      increase in serum titers of anti-acetylcholine receptor autoantibodies (P=8 x 10(
      6)). Remarkably, this effect was suppressed by a second locus in cis on the 8.1
      haplotype and located toward the class II region. Altogether, these data
      demonstrate the highly significant but complex effects of the 8.1 haplotype on
      the phenotype of myasthenia gravis patients and might shed light on its role in
      other autoimmune diseases.

PMID- 15489266
TI  - A totally synthetic vaccine of generic structure that targets Toll-like receptor
      2 on dendritic cells and promotes antibody or cytotoxic T cell responses.
AB  - A simple generic peptide-based vaccine structure that targets Toll-like receptor
      2-expressing dendritic cells and causes their activation is described. The
      vaccines are totally synthetic, serve as their own adjuvant, and are composed of
      (i) a single helper T cell epitope, (ii) a target epitope that is either
      recognized by CD8+ T cells or B cells, and (iii) a Toll-like receptor 2-targeting
      lipid moiety, S-[2,3-bis(palmitoyloxy)propyl]cysteine, that is situated between
      the peptide epitopes to form a branched configuration. The different CD8+ T cell
      epitopes examined were from (i) influenza virus, (ii) the intracellular bacterium
      Listeria monocytogenes, and (iii) ovalbumin as a model tumor antigen. Vaccines
      containing a B cell epitope from gastrin or luteinizing hormone-releasing hormone
      as a B cell epitope were also examined for their ability to elicit antibody
      against the parent hormones. Each of the vaccines was capable of inducing either
      CD8+ T cell or antibody-mediated immune responses. The lipidated vaccines, but
      not the nonlipidated vaccines, were able to mediate protection against viral or
      bacterial infection and mediate prophylactic and therapeutic anticancer activity.
      The two hormone-based vaccines induced high antibody titers, which in the case of
      luteinizing hormone-releasing hormone resulted in abrogation of reproductive
      function. These results highlight the utility of simple, totally synthetic,
      epitope-based vaccines.

PMID- 15489267
TI  - Default brain functionality in blind people.
AB  - We studied whether default functionality of the human brain, as revealed by task
      independent decreases in activity occurring during goal-directed behaviors, is
      functionally reorganized by blindness. Three groups of otherwise normal adults
      were studied: early blind, adventitiously blind, and normally sighted. They were
      imaged by using functional MRI during performance of a word association task
      (verb generation to nouns) administered by using auditory stimuli in all groups
      and Braille reading in blind participants. In sighted people, this task normally
      produces robust task-independent decreases relative to a baseline of quiet
      wakefulness with eyes closed. Our functional MRI results indicate that task
      independent decreases are qualitatively similar across all participant groups in
      medial and dorsal prefrontal, lateral parietal, anterior precuneus, and posterior
      cingulate cortices. Similarities in task-independent decreases are consistent
      with the hypothesis that functional reorganization resulting from the absence of
      a particular sensory modality does not qualitatively affect default functionality
      as revealed by task-independent decreases. More generally, these results support
      the notion that the brain largely operates intrinsically, with sensory
      information modulating rather than determining system operations.

PMID- 15489268
TI  - The polyproline II conformation in short alanine peptides is noncooperative.
AB  - The finding that short alanine peptides possess a high fraction of polyproline II
      (PII) structure (Phi=-75 degrees, Psi=+145 degrees ) at low temperature has broad
      implications for unfolded states of proteins. An important question concerns
      whether or not this structure is locally determined or cooperative. We have
      monitored the conformation of alanine in a series of model peptides AcGGAnGGNH2
      (n=1-3) over a temperature range from -10 degrees C to +80 degrees C. Use of 15N
      labeled alanine substitutions makes it possible to measure 3JalphaN coupling
      constants accurately over the full temperature range. Based on a 1D next-neighbor
      model, the cooperative parameter sigma of PII nucleation is evaluated from the
      coupling constant data. The finding that sigma is close to unity (1 +/- 0.2)
      indicates a noncooperative role for alanine in PII structure formation,
      consistent with statistical surveys of the Protein Data Bank that suggest that
      most PII structure occurs in isolated residues. Lack of cooperativity in these
      models implies that hydration effects that influence PII conformation in water
      are highly localized. Using a nuclear Overhauser effect ratio strategy to define
      the alanine Psi angle, we estimate that, at 40 degrees C, the time-averaged
      alanine conformation (Phi=-80 degrees, Psi=+170 degrees ) deviates from canonical
      PII structure, indicating that PII melts at high temperature. Thus, the high
      temperature state of short alanine peptides seems to be an unfolded ensemble with
      higher distribution in the extended beta structure basin, but not a coil.

PMID- 15489269
TI  - Chemical and electrical synapses perform complementary roles in the
      synchronization of interneuronal networks.
AB  - Electrical and chemical synapses exist within the same networks of inhibitory
      cells, and each kind of synapse is known to be able to foster synchrony among
      oscillating neurons. Using numerical and analytical techniques, we show here that
      the electrical and inhibitory coupling play different roles in the
      synchronization of rhythms in inhibitory networks. The parameter range chosen is
      motivated by gamma rhythms, in which the gamma-aminobutyric acid type A (GABAA)
      mediated inhibition is relatively strong. Under this condition, addition of a
      small electrical conductance can increase the degree of synchronization far more
      than a much larger increase in inhibitory conductance. The inhibitory synapses
      act to eliminate the effects of different initial conditions, whereas the
      electrical synapses mitigate suppression of firing due to heterogeneity in the
      network. Analytical techniques include tracking trajectories of coupled cells
      between spikes; the analysis shows that, in networks in which the degree of
      excitability is heterogeneous, inhibition can increase the dispersion of the
      voltages between spikes, whereas electrical coupling reduces such dispersion.

PMID- 15489270
TI  - Unveiling functional protein motions with picosecond x-ray crystallography and
      molecular dynamics simulations.
AB  - A joint analysis of all-atom molecular dynamics (MD) calculations and picosecond
      time-resolved x-ray structures was performed to gain single-molecule insights
      into mechanisms of protein function. Ensemble-averaged MD simulations of the L29F
      mutant of myoglobin after ligand dissociation reproduce the direction, amplitude,
      and time scales of crystallographically determined structural changes. This close
      agreement with experiments at comparable resolution in space and time validates
      the individual MD trajectories. From 1,700 single-molecule trajectories, we
      identified and structurally characterized a conformational switch that directs
      dissociated ligands to one of two nearby protein cavities. Subsequent ligand
      migration proceeds through a network of transiently interconnected internal
      cavities, with passage between them involving correlated protein-ligand motions.
      The simulations also suggest how picosecond protein motions modulate the
      functional dissociation of oxygen and suppress the geminate recombination of
      toxic carbon monoxide.

PMID- 15489271
TI  - Gene targeting in yeast is initiated by two independent strand invasions.
AB  - To study the mechanism of gene targeting, we examined heteroduplex DNA (hDNA)
      formation during targeting of two separate chromosomal locations in Saccharomyces
      cerevisiae. We examined both replacement of the entire gene with a heterologous
      selectable marker and correction of a single base pair insertion mutation by gene
      targeting, and in all cases our results were consistent with separate strand
      invasion/resolution at the two ends of the targeting fragment as the dominant
      mechanism in wild-type cells. A small subset of transformants was consistent with
      assimilation of a single strand of targeting DNA encompassing both flanking
      homology regions and the marker into hDNA. hDNA formation during correction of a
      point mutation by targeted integration was conspicuously altered in a mismatch
      repair-deficient background and was consistent with single-strand
      invasion/assimilation without mismatch correction, confirming that gene targeting
      by this pathway is actively impeded in wild-type yeast. Finally, inversion of one
      targeted locus and mutation of an active origin of DNA replication at the other
      locus affected hDNA formation significantly, suggesting that formation of
      productive interactions between the targeting DNA and the targeted site in the
      chromosome is sensitive to local DNA dynamics.

PMID- 15489272
TI  - Dissociation of spatial attention and saccade preparation.
AB  - The goal of this experiment was to determine whether the allocation of attention
      necessarily requires saccade preparation. To dissociate the focus of attention
      from the endpoint of a saccade, macaque monkeys were trained to perform visual
      search for a uniquely colored rectangle and shift gaze either toward or opposite
      this color singleton according to its orientation. A vertical singleton cued a
      prosaccade, a horizontal singleton, an antisaccade. Saccade preparation was
      probed by measuring the direction of saccades evoked by intracortical
      microstimulation of the frontal eye fields at variable times after presentation
      of the search array. Eye movements evoked on prosaccade trials deviated
      progressively toward the singleton that was also the endpoint of the correct eye
      movement. However, eye movements evoked on antisaccade trials never deviated
      toward the singleton but only progressively toward the location opposite the
      singleton. This occurred even though previous work showed that on antisaccade
      trials most neurons in frontal eye fields initially select the singleton while
      attention is allocated to distinguish its shape. Thus, sensorimotor structures
      can covertly orient attention without preparing a saccade.

PMID- 15489273
TI  - Ceramide, a target for antiretroviral therapy.
AB  - Studies of ceramide metabolism and function in a wide range of biological
      processes have revealed a role for this lipid in regulating key cellular
      responses. Our research on the role of sphingolipids in HIV entry has led to the
      hypothesis that modulation of ceramide levels in target cells affects their
      susceptibility to HIV infection by rearranging HIV receptors. Cellular ceramide
      levels were modulated by application of pharmacological agents such as N-(4
      hydroxyphenyl)retinamide (4-HPR, fenretinide), by treatment with sphingomyelinase
      (Smase), or by exogenous addition of long-chain ceramide, and determined after
      metabolic incorporation of [3H]sphingosine. Infectivity assays were performed by
      using a HeLa-derived indicator cell line, TZM-bl, CD4+ lymphocytes, and
      monocytes. We observed a dose-dependent inhibition by 4-HPR of infection of TZM
      bl cells by a broad range of HIV-1 isolates at low micromolar concentrations with
      an IC50 of <1 microM for most isolates tested. Nearly complete inhibition was
      seen at 5 microM, a dose that enhanced ceramide levels by 50-100%, yet was
      nontoxic to the cells. Treating cells with other pharmacological agents that
      enhanced ceramide levels, with Smase, or exogenous addition of long-chain
      ceramide also resulted in inhibition of HIV-1 infection. Enhancing ceramide
      levels in CD4+ lymphocytes and in monocyte-derived macrophages with 4-HPR or
      Smase significantly reduced infectivity without toxicity. The minimal toxicity of
      normal cells exposed to 4-HPR should make the drug exceedingly suitable as an
      anti-HIV therapeutic.

PMID- 15489274
TI  - Estimating genome conservation between crop and model legume species.
AB  - Legumes are simultaneously one of the largest families of crop plants and a
      cornerstone in the biological nitrogen cycle. We combined molecular and
      phylogenetic analyses to evaluate genome conservation both within and between the
      two major clades of crop legumes. Genetic mapping of orthologous genes identifies
      broad conservation of genome macrostructure, especially within the galegoid
      legumes, while also highlighting inferred chromosomal rearrangements that may
      underlie the variation in chromosome number between these species. As a
      complement to comparative genetic mapping, we compared sequenced regions of the
      model legume Medicago truncatula with those of the diploid Lotus japonicus and
      the polyploid Glycine max. High conservation was observed between the genomes of
      M. truncatula and L. japonicus, whereas lower levels of conservation were evident
      between M. truncatula and G. max. In all cases, conserved genome microstructure
      was punctuated by significant structural divergence, including frequent
      insertion/deletion of individual genes or groups of genes and lineage-specific
      expansion/contraction of gene families. These results suggest that comparative
      mapping may have considerable utility for basic and applied research in the
      legumes, although its predictive value is likely to be tempered by phylogenetic
      distance and genome duplication.

PMID- 15489275
TI  - Elemental composition of airway surface liquid in the pig determined by x-ray
      microanalysis.
AB  - The ionic composition of the airway surface liquid (ASL) is of importance in
      cystic fibrosis and exercise-induced asthma. However, literature data on the
      composition of the ASL vary markedly. The aim of the study was to determine the
      composition of the ASL, using two different methods involving minimal
      manipulation. In one method, the composition of the ASL was measured by X-ray
      microanalysis of frozen-hydrated samples. In the second method, small dextran
      beads were equilibrated with the ASL in a moisture chamber, isolated, dried, and
      analyzed. Plasma or serum from the same pigs was also analyzed. Both methods
      showed that the Na and Cl concentrations in the ASL are close to the
      concentrations of these ions in plasma. X-ray microanalysis of frozen-hydrated
      ASL showed significantly higher K, P, and S because here the upper layer
      (containing cell debris and secreted mucus) is sampled, whereas the bead method
      samples the watery component of the ASL. Ultrastructural analysis of the
      epithelium at various osmotic values showed evident damage at concentrations of
      50 mM or less. These data support the notion that the physiologically important
      watery component of the pig ASL has an ionic composition close to that of plasma.

PMID- 15489276
TI  - Untranslated regions from C4 amaranth AhRbcS1 mRNAs confer translational
      enhancement and preferential bundle sheath cell expression in transgenic C4
      Flaveria bidentis.
AB  - Many aspects of photosynthetic gene expression are posttranscriptionally
      regulated in C4 plants. To determine if RbcS mRNA untranslated regions (UTRs) in
      themselves could confer any characteristic C4 expression patterns, 5'- and 3'
      UTRs of AhRbcS1 mRNA from the C4 dicot amaranth were linked to a gusA reporter
      gene. These were constitutively transcribed from a cauliflower mosaic virus
      promoter and assayed for posttranscriptional expression patterns in transgenic
      lines of the C4 dicot Flaveria bidentis. Three characteristic C4 expression
      patterns were conferred by heterologous AhRbcS1 UTRs in transgenic F. bidentis.
      First, the AhRbcS1 UTRs conferred strong translational enhancement of gusA
      expression, relative to control constructs lacking these UTRs. Second, while the
      UTRs did not appear to confer tissue-specific expression when analyzed by beta
      glucuronidase activity assays, differences in gusA mRNA accumulation were
      observed in leaves, stems, and roots. Third, the AhRbcS1 UTRs conferred
      preferential gusA expression (enzyme activity and gusA mRNA accumulation) in leaf
      bundle sheath cells. AhRbcS1 UTR-mediated translational enhancement was also
      observed in transgenic C3 plants (tobacco [Nicotiana tabacum]) and in in vitro
      translation extracts. These mRNAs appear to be translated with different
      efficiencies in C4 versus C3 plants, indicating that processes determining
      overall translational efficiency may vary between these two categories of higher
      plants. Our findings suggest that the AhRbcS1 5'-UTR functions as a strong
      translational enhancer in leaves and other tissues, and may work synergistically
      with the 3'-UTR to modulate overall levels of Rubisco gene expression in
      different tissues and cell types of C4 plants.

PMID- 15489277
TI  - Pharmacological evidence that multiple phospholipid signaling pathways link
      Rhizobium nodulation factor perception in Medicago truncatula root hairs to
      intracellular responses, including Ca2+ spiking and specific ENOD gene
      expression.
AB  - Rhizobium nodulation (Nod) factors are specific lipochito-oligosaccharide signals
      essential for initiating in root hairs of the host legume developmental responses
      that are required for controlled entry of the microsymbiont. In this article, we
      focus on the Nod factor signal transduction pathway leading to specific and cell
      autonomous gene activation in Medicago truncatula cv Jemalong in a study making
      use of the Nod factor-inducible MtENOD11 gene. First, we show that
      pharmacological antagonists that interfere with intracellular ion channel and
      Ca2+ pump activities are efficient blockers of Nod factor-elicited pMtENOD11-beta
      glucuronidase (GUS) expression in root hairs of transgenic M. truncatula. These
      results indicate that intracellular Ca2+ release and recycling activities,
      essential for Ca2+ spiking, are also required for specific gene activation.
      Second, pharmacological effectors that inhibit phospholipase D and
      phosphoinositide-dependent phospholipase C activities are also able to block
      pMtENOD11-GUS activation, thus underlining a central role for multiple
      phospholipid signaling pathways in Nod factor signal transduction. Finally,
      pMtENOD11-GUS was introduced into all three Nod-/Myc- dmi M. truncatula mutant
      backgrounds, and gene expression was evaluated in response to the mastoparan
      peptide agonist Mas7. We found that Mas7 elicits root hair MtENOD11 expression in
      dmi1 and dmi2 mutants, but not in the dmi3 mutant, suggesting that the agonist
      acts downstream of DMI1/DMI2 and upstream of DMI3. In light of these results and
      the recently discovered identities of the DMI gene products, we propose an
      integrated cellular model for Nod factor signaling in legume root hairs in which
      phospholipids play a key role in linking the Nod factor perception apparatus to
      downstream components such as Ca2+ spiking and ENOD gene expression.

PMID- 15489278
TI  - Unexpected deposition patterns of recombinant proteins in post-endoplasmic
      reticulum compartments of wheat endosperm.
AB  - Protein transport within cereal endosperm cells is complicated by the abundance
      of endoplasmic reticulum (ER)-derived and vacuolar protein bodies. For wheat
      storage proteins, two major transport routes run from the ER to the vacuole, one
      bypassing and one passing through the Golgi. Proteins traveling along each route
      converge at the vacuole and form aggregates. To determine the impact of this
      trafficking system on the fate of recombinant proteins expressed in wheat
      endosperm, we used confocal and electron microscopy to investigate the fate of
      three recombinant proteins containing different targeting information. KDEL
      tagged recombinant human serum albumin, which is retrieved to the ER lumen in
      leaf cells, was deposited in prolamin aggregates within the vacuole of endosperm
      cells, most likely following the bulk of endogenous glutenins. Recombinant fungal
      phytase, a glycoprotein designed for secretion, was delivered to the same
      compartment, with no trace of the molecule in the apoplast. Glycan analysis
      revealed that this protein had passed through the Golgi. The localization of
      human serum albumin and phytase was compared to that of recombinant legumin,
      which contains structural targeting information directing it to the vacuole.
      Uniquely, legumin accumulated in the globulin inclusion bodies at the periphery
      of the prolamin bodies, suggesting a different mode of transport and/or
      aggregation. Our results demonstrate that recombinant proteins are deposited in
      an unexpected pattern within wheat endosperm cells, probably because of the
      unique storage properties of this tissue. Our data also confirm that recombinant
      proteins are invaluable tools for the analysis of protein trafficking in cereals.

PMID- 15489279
TI  - Ca2+ dynamics in a pollen grain and papilla cell during pollination of
      Arabidopsis.
AB  - Ca2+ dynamics in the growing pollen tube have been well documented in vitro using
      germination assays and Ca2+ imaging techniques. However, very few in vivo studies
      of Ca2+ in the pollen grain and papilla cell during pollination have been
      performed. We expressed yellow cameleon, a Ca2+ indicator based on green
      fluorescent protein, in the pollen grains and papilla cells of Arabidopsis
      (Arabidopsis thaliana) and monitored Ca2+ dynamics during pollination. In the
      pollen grain, [Ca2+]cyt increased at the potential germination site soon after
      hydration and remained augmented until germination. As in previous in vitro
      germination studies, [Ca2+]cyt oscillations were observed in the tip region of
      the growing pollen tube, but the oscillation frequency was faster and [Ca2+]cyt
      was higher than had been observed in vitro. In the pollinated papilla cell,
      remarkable increases in [Ca2+]cyt occurred three times in succession, just under
      the site of pollen-grain attachment. [Ca2+]cyt increased first soon after pollen
      hydration, with a second increase occurring after pollen protrusion. The third
      and most remarkable [Ca2+]cyt increase took place when the pollen tube penetrated
      into the papilla cell wall.

PMID- 15489281
TI  - Possible influence of cell walls upon ion concentrations at plasma membrane
      surfaces. Toward a comprehensive view of cell-surface electrical effects upon ion
      uptake, intoxication, and amelioration.
AB  - Plant uptake of ions, intoxication by ions, and the alleviation of intoxication
      by other ions often correlate poorly with ion concentrations in the rooting
      medium. By contrast, uptake, intoxication, and alleviation correlate well with
      ion concentrations at the plasma membrane (PM) surface computed as though the PM
      were bathed directly in the rooting medium with no effect from the cell wall
      (CW). According to two separate lines of analysis, a close association of CWs and
      PMs results in a slight increase in cation concentrations and a slight decrease
      in anion concentrations at the PM surface compared with concentrations when the
      CW is separated or has no effect. Although slightly different, the ion
      concentrations at the PM surface computed with and without close association with
      the CW are highly correlated. Altogether, the CW would appear to have a small
      effect upon ion uptake by the PM or upon intoxication or alleviation of
      intoxication originating at the PM surface. These analyses have been enabled by
      the recent evaluation of parameters required for the electrostatic models (Gouy
      Chapman-Stern and Donnan-plus-binding) used to compute electrical potentials and
      ion concentrations in CWs and at PM surfaces.

PMID- 15489280
TI  - Cesium toxicity in Arabidopsis.
AB  - Cesium (Cs) is chemically similar to potassium (K). However, although K is an
      essential element, Cs is toxic to plants. Two contrasting hypotheses to explain
      Cs toxicity have been proposed: (1) extracellular Cs+ prevents K+ uptake and,
      thereby, induces K starvation; and (2) intracellular Cs+ interacts with vital
      K(+)-binding sites in proteins, either competitively or noncompetitively,
      impairing their activities. We tested these hypotheses with Arabidopsis
      (Arabidopsis thaliana). Increasing the Cs concentration in the agar ([Cs](agar))
      on which Arabidopsis were grown reduced shoot growth. Increasing the K
      concentration in the agar ([K](agar)) increased the [Cs](agar) at which Cs
      toxicity was observed. However, although increasing [Cs](agar) reduced shoot K
      concentration ([K](shoot)), the decrease in shoot growth appeared unrelated to
      [K](shoot) per se. Furthermore, the changes in gene expression in Cs-intoxicated
      plants differed from those of K-starved plants, suggesting that Cs intoxication
      was not perceived genetically solely as K starvation. In addition to reducing
      [K](shoot), increasing [Cs](agar) also increased shoot Cs concentration
      ([Cs](shoot)), but shoot growth appeared unrelated to [Cs](shoot) per se. The
      relationship between shoot growth and [Cs](shoot)/[K](shoot) suggested that, at a
      nontoxic [Cs](shoot), growth was determined by [K](shoot) but that the growth of
      Cs-intoxicated plants was related to the [Cs](shoot)/[K](shoot) quotient. This is
      consistent with Cs intoxication resulting from competition between K+ and Cs+ for
      K(+)-binding sites on essential proteins.

PMID- 15489282
TI  - Ethylene biology. More than a gas.

PMID- 15489283
TI  - The Cell Wall Navigator database. A systems-based approach to organism
      unrestricted mining of protein families involved in cell wall metabolism.

PMID- 15489284
TI  - Transcriptional similarities, dissimilarities, and conservation of cis-elements
      in duplicated genes of Arabidopsis.
AB  - In plants, duplication of individual genes, long chromosomal regions, and
      complete genomes provides a major source for evolutionary innovation. We
      investigated two different types of duplications, tandem and segmental
      duplications, in Arabidopsis for correlation, conservation, and differences of
      expression characteristics by making use of large genome-wide expression data as
      measured by the massively parallel signature sequencing method. Our analysis
      indicates that large fractions of duplicated gene pairs still share
      transcriptional characteristics. However, our results also indicate that
      expression divergence occurs frequently between duplicated gene pairs, a process
      which frequently might be employed for the retention of sequence redundant gene
      pairs. Preserved overall similarity between promoters of duplicated genes as well
      as preservation of individual cis-elements within the respective promoters
      indicates that the process of transcriptional neo- and subfunctionalization is
      restricted to only a fraction of cis-elements. We show that sequence similarities
      and shared regulatory properties within duplicated promoters provide a powerful
      means to undertake large-scale cis-regulatory element identification by applying
      an intragenomic phylogenetic footprinting approach. Our work lays a foundation
      for future comparative studies to elucidate the molecular manifestation of
      regulatory similarities and dissimilarities of duplicated genes.

PMID- 15489285
TI  - Maximizing the efficacy of SAGE analysis identifies novel transcripts in
      Arabidopsis.
AB  - The efficacy of using Serial Analysis of Gene Expression (SAGE) to analyze the
      transcriptome of the model dicotyledonous plant Arabidopsis was assessed. We
      describe an iterative tag-to-gene matching process that exploits the availability
      of the whole genome sequence of Arabidopsis. The expression patterns of 98% of
      the annotated Arabidopsis genes could theoretically be evaluated through SAGE and
      using an iterative matching process 79% could be identified by a tag found at a
      unique site in the genome. A total of 145,170 reliable experimental tags from two
      Arabidopsis leaf tissue SAGE libraries were analyzed, of which 29,632 were
      distinct. The majority (93%) of the 12,988 experimental tags observed greater
      than once could be matched within the Arabidopsis genome. However, only 78% were
      matched to a single locus within the genome, reflecting the complexities
      associated with working in a highly duplicated genome. In addition to a
      comprehensive assessment of gene expression in Arabidopsis leaf tissue, we
      describe evidence of transcription from pseudo-genes as well as evidence of
      alternative mRNA processing and anti-sense transcription. This collection of
      experimental SAGE tags could be exploited to assist in the on-going annotation of
      the Arabidopsis genome.

PMID- 15489286
TI  - Genome-wide mRNA surveillance is coupled to mRNA export.
AB  - Nuclear export of mRNA is a central step in gene expression that shows extensive
      coupling to transcription and transcript processing. However, little is known
      about the fate of mRNA and its export under conditions that damage the DNA
      template and RNA itself. Here we report the discovery of four new factors
      required for mRNA export through a screen of all annotated nonessential
      Saccharomyces cerevisiae genes. Two of these factors, mRNA surveillance factor
      Rrp6 and DNA repair protein Lrp1, are nuclear exosome components that physically
      interact with one another. We find that Lrp1 mediates specific mRNA degradation
      upon DNA-damaging UV irradiation as well as general mRNA degradation. Lrp1
      requires Rrp6 for genomic localization to genes encoding its mRNA targets, and
      Rrp6 genomic localization in turn correlates with transcription. Further, Rrp6
      and Lrp1 are both required for repair of UV-induced DNA damage. These results
      demonstrate coupling of mRNA surveillance to mRNA export and suggest specificity
      of the RNA surveillance machinery for different transcript populations. Broadly,
      these findings link DNA and RNA surveillance to mRNA export.

PMID- 15489287
TI  - Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: cooperativity of
      Ink4a/ARF and Trp53 loss of function.
AB  - Alveolar rhabdomyosarcoma is an aggressive childhood muscle cancer for which
      outcomes are poor when the disease is advanced. Although well-developed mouse
      models exist for embryonal and pleomorphic rhabdomyosarcomas, neither a
      spontaneous nor a transgenic mouse model of alveolar rhabdomyosarcoma has yet
      been reported. We report the first mouse model of alveolar rhabdomyosarcoma using
      a conditional Pax3:Fkhr knock-in allele whose activation in late embryogenesis
      and postnatally is targeted to terminally differentiating Myf6-expressing
      skeletal muscle. In these mice, alveolar rhabdomyosarcomas occur but at low
      frequency, and Fkhr haploinsufficiency does not appear to accelerate
      tumorigenesis. However, Pax3:Fkhr homozygosity with accompanying Ink4a/ARF or
      Trp53 pathway disruption, by means of conditional Trp53 or Ink4a/ARF loss of
      function, substantially increases the frequencies of tumor formation. These
      results of successful tumor generation postnatally from a target pool of
      differentiating myofibers are in sharp contrast to the birth defects and lack of
      tumors for mice with prenatal and postnatal satellite cell triggering of
      Pax3:Fkhr. Furthermore, these murine alveolar rhabdomyosarcomas have an
      immunohistochemical profile similar to human alveolar rhabdomyosarcoma,
      suggesting that this conditional mouse model will be relevant to study of the
      disease and will be useful for preclinical therapeutic testing.

PMID- 15489288
TI  - Telomerase- and recombination-independent immortalization of budding yeast.
AB  - It is generally assumed that there are only two ways to maintain the ends of
      chromosomes in yeast and mammalian nuclei: telomerase and recombination. Without
      telomerase and recombination, cells enter senescence, a state of permanent growth
      arrest. We found that the decisive role in preventing senescent budding yeast
      cells from dividing is played by the Exo1 nuclease. In the absence of Exo1,
      telomerase- and recombination-defective yeast can resume cell cycle progression,
      despite degradation of telomeric regions from many chromosomes. As degradation
      progresses toward internal chromosomal regions, a progressive decrease in
      viability would be expected, caused by loss of essential genes. However, this was
      not the case. We demonstrate that extensive degradation and loss of essential
      genes can be efficiently prevented through a little-studied mechanism of DNA
      double-strand-break repair, in which short DNA palindromes induce formation of
      large DNA palindromes. For the first time, we show that large palindromes form as
      a natural consequence of postsenescence growth and that they become essential for
      immortalization in the absence of telomerase activity.

PMID- 15489289
TI  - What better measure than ribosome synthesis?

PMID- 15489290
TI  - Elongation by RNA polymerase II: the short and long of it.
AB  - Appreciable advances into the process of transcript elongation by RNA polymerase
      II (RNAP II) have identified this stage as a dynamic and highly regulated step of
      the transcription cycle. Here, we discuss the many factors that regulate the
      elongation stage of transcription. Our discussion includes the classical
      elongation factors that modulate the activity of RNAP II, and the more recently
      identified factors that facilitate elongation on chromatin templates.
      Additionally, we discuss the factors that associate with RNAP II, but do not
      modulate its catalytic activity. Elongation is highlighted as a central process
      that coordinates multiple stages in mRNA biogenesis and maturation.

PMID- 15489291
TI  - The active spatial organization of the beta-globin locus requires the
      transcription factor EKLF.
AB  - Three-dimensional organization of a gene locus is important for its regulation,
      as recently demonstrated for the beta-globin locus. When actively expressed, the
      cis-regulatory elements of the beta-globin locus are in proximity in the nuclear
      space, forming a compartment termed the Active Chromatin Hub (ACH). However, it
      is unknown which proteins are involved in ACH formation. Here, we show that EKLF,
      an erythroid transcription factor required for adult beta-globin gene
      transcription, is also required for ACH formation. We conclude that transcription
      factors can play an essential role in the three-dimensional organization of gene
      loci.

PMID- 15489292
TI  - RNA polymerase I transcription and pre-rRNA processing are linked by specific SSU
      processome components.
AB  - Sequential events in macromolecular biosynthesis are often elegantly coordinated.
      The small ribosomal subunit (SSU) processome is a large ribonucleoprotein (RNP)
      required for processing of precursors to the small subunit RNA, the 18S, of the
      ribosome. We have found that a subcomplex of SSU processome proteins, the t-Utps,
      is also required for optimal rRNA transcription in vivo in the yeast
      Saccharomyces cerevisiae. The t-Utps are ribosomal chromatin (r-chromatin)
      associated, and they exist in a complex in the absence of the U3 snoRNA.
      Transcription is required neither for the formation of the subcomplex nor for its
      r-chromatin association. The t-Utps are associated with the pre-18S rRNAs
      independent of the presence of the U3 snoRNA. This association may thus represent
      an early step in the formation of the SSU processome. Our results indicate that
      rRNA transcription and pre-rRNA processing are coordinated via specific
      components of the SSU processome.

PMID- 15489293
TI  - A nuclear isoform of the focal adhesion LIM-domain protein Trip6 integrates
      activating and repressing signals at AP-1- and NF-kappaB-regulated promoters.
AB  - Glucocorticoid receptor (GR)-mediated transrepression of the transcription
      factors AP-1 and NF-kappaB, responsible for most of the anti-inflammatory effects
      of glucocorticoids, is initiated by the tethering of GR to the promoters of
      target genes. We report that this tethering is mediated by a nuclear isoform of
      the focal adhesion LIM domain protein Trip6. Trip6 functions as a coactivator for
      both AP-1 and NF-kappaB. As shown by chromatin immunoprecipitation, Trip6 is
      recruited to the promoters of target genes together with AP-1 or NF-kappaB. In
      the presence of glucocorticoids, GR joins the Trip6 complex. Reducing the level
      of Trip6 by RNA interference or abolishing its interaction with GR by dominant
      negative mutation eliminates transrepression. We propose that GR tethering to the
      target promoter through Trip6 forms the basis of transrepression, and that Trip6
      exerts its nuclear functions by acting as a molecular platform, enabling target
      promoters to integrate activating or repressing signals.

PMID- 15489294
TI  - Identification of C. elegans DAF-12-binding sites, response elements, and target
      genes.
AB  - Intracellular receptor DAF-12 regulates dauer formation and developmental age and
      affects Caenorhabditis elegans lifespan. Genetic analyses place DAF-12 at the
      convergence of several signal transduction pathways; however, the downstream
      effectors and the molecular basis for the receptor's multiple physiological
      outputs are unknown. Beginning with C. elegans genomic DNA, we devised a
      procedure for multiple rounds of selection and amplification that yielded
      fragments bearing DAF-12-binding sites. These genomic fragments mediated DAF-12
      dependent transcriptional regulation both in Saccharomyces cerevisiae and in C.
      elegans; that is, they served as functional DAF-12 response elements. We
      determined that most of the genomic fragments that displayed DAF-12 response
      element activity in yeast were linked to genes that were regulated by DAF-12 in
      C. elegans; indeed, the response element-containing fragments typically resided
      within clusters of DAF-12-regulated genes. DAF-12 target gene regulation was
      developmental program and stage specific, potentially predicting a fit of these
      targets into regulatory networks governing aspects of C. elegans reproductive
      development and dauer formation.

PMID- 15489295
TI  - The geminivirus nuclear shuttle protein is a virulence factor that suppresses
      transmembrane receptor kinase activity.
AB  - Despite the large number of leucine-rich-repeat (LRR) receptor-like-kinases
      (RLKs) in plants and their conceptual relevance in signaling events, functional
      information is restricted to a few family members. Here we describe the
      characterization of new LRR-RLK family members as virulence targets of the
      geminivirus nuclear shuttle protein (NSP). NSP interacts specifically with three
      LRR-RLKs, NIK1, NIK2, and NIK3, through an 80-amino acid region that encompasses
      the kinase active site and A-loop. We demonstrate that these NSP-interacting
      kinases (NIKs) are membrane-localized proteins with biochemical properties of
      signaling receptors. They behave as authentic kinase proteins that undergo
      autophosphorylation and can also phosphorylate exogenous substrates.
      Autophosphorylation occurs via an intermolecular event and oligomerization
      precedes the activation of the kinase. Binding of NSP to NIK inhibits its kinase
      activity in vitro, suggesting that NIK is involved in antiviral defense response.
      In support of this, infectivity assays showed a positive correlation between
      infection rate and loss of NIK1 and NIK3 function. Our data are consistent with a
      model in which NSP acts as a virulence factor to suppress NIK-mediated antiviral
      responses.

PMID- 15489296
TI  - The Arabidopsis MutS homolog AtMSH4 functions at an early step in recombination:
      evidence for two classes of recombination in Arabidopsis.
AB  - MSH4, a meiosis-specific member of the MutS-homolog family of genes, is required
      for normal levels of recombination and fertility in budding yeast, mouse, and
      Caenorhabditis elegans. In this paper, we report the identification and
      characterization of the Arabidopsis homolog of MSH4 (AtMSH4). We demonstrate that
      AtMSH4 expression can only be detected in floral tissues, consistent with a role
      in reproduction. Immunofluorescence studies indicate that its expression is
      limited to early meiotic prophase I, preceding the synapsis of homologous
      chromosomes. A T-DNA insertional mutant (Atmsh4) exhibited normal vegetative
      growth but a severe reduction in fertility, consistent with a meiotic defect;
      this was confirmed by cytological analysis of meiosis. RNAi-induced down
      regulation of the MSH4 gene resulted in a similar fertility and meiotic
      phenotype. We demonstrate that prophase I chromosome synapsis is delayed and may
      be incomplete in Atmsh4, and metaphase I chiasma frequency is greatly reduced to
      approximately 15% of wild type, leading to univalence and nondisjunction. We show
      that these residual chiasmata are randomly distributed among cells and
      chromosomes. These features of chiasma frequency and distribution in Atmsh4 show
      close parallels to MSH4-independent crossovers in budding yeast that have been
      proposed to originate by a separate pathway. Furthermore, the characteristics of
      the MSH4-independent chiasmata in the Atmsh4 mutant closely parallel those of
      second-pathway crossovers that have been postulated from Arabidopsis crossover
      analysis and mathematical modeling. Taken together, this evidence strongly
      indicates that Arabidopsis possesses two crossover pathways.

PMID- 15489297
TI  - Structural characterization of cationic liposomes loaded with sugar-based
      carboranes.
AB  - In this article we report the physicochemical characterization of cationic
      liposomes loaded with orthocarborane and two of its sugar-containing derivatives.
      Carboranes are efficient boron delivery agents in boron neutron capture therapy,
      an anti-cancer treatment based on neutron absorption by 10B nuclei. Cationic
      liposomes were prepared using the positively charged DOTAP and the zwitterionic
      DOPE, as a helper lipid. These liposomes are currently used in gene therapy for
      their ability in targeting the cell nucleus; therefore they can be considered
      appropriate vectors for boron neutron capture therapy, in the quest of reducing
      the high boron amount that is necessary for successful cancer treatment. Boron
      uptake was determined by an original in situ method, based on neutron absorption.
      The structural properties of the loaded liposomes were studied in detail by the
      combined use of small angle x-ray scattering and small angle neutron scattering.
      These techniques established the global shape and size of liposomes and their
      bilayer composition. The results were discussed in term of molecular properties
      of the hosted drugs. Differences found in the insertion modality were correlated
      with the preparation procedure or with the specific shape and lipophilic
      hydrophilic balance of each carborane.

PMID- 15489298
TI  - Shape transitions and lattice structuring of ceramide-enriched domains generated
      by sphingomyelinase in lipid monolayers.
AB  - Sphingomyelinases (SMases) hydrolyze the membrane constituent sphingomyelin (SM)
      to phosphocholine and ceramide (Cer). Growing evidence supports that SMase
      induced SM-->Cer conversion leads to the formation of lateral Cer-enriched
      domains which drive structural reorganization in lipid membranes. We previously
      provided visual evidence in real-time for the formation of Cer-enriched domains
      in SM monolayers through the action of the neutral Bacillus cereus SMase. In this
      work, we disclose a succession of discrete morphologic transitions and lateral
      organization of Cer-enriched domains that underlay the SMase-generated surface
      topography. We further reveal how these structural parameters couple to the
      generation of two-dimensional electrostatic fields, based upon the specific
      orientation of the lipid dipole moments in the Cer-enriched domains. Advanced
      image processing routines in combination with time-resolved epifluorescence
      microscopy on Langmuir monolayers revealed: 1), spontaneous nucleation and
      circular growth of Cer-enriched domains after injection of SMase into the
      subphase of the SM monolayer; 2), domain-intrinsic discrete transitions from
      circular to periodically undulating shapes followed by a second transition toward
      increasingly branched morphologies; 3), lateral superstructure organization into
      predominantly hexagonal domain lattices; 4), formation of super-superstructures
      by the hexagonal lattices; and 5), rotationally and laterally coupled domain
      movement before domain border contact. All patterns proved to be specific for the
      SMase-driven system since they could not be observed with Cer-enriched domains
      generated by defined mixtures of SM/Cer in enzyme-free monolayers at the same
      surface pressure (pi = 10 mN/m). Following the theories of lateral shape
      transitions, dipolar electrostatic interactions of lipid domains, and direct
      determinations of the monolayer dipole potential, our data show that SMase
      induces a domain-specific packing and orientation of the molecular dipole moments
      perpendicular to the air/water interface. In consequence, protein-driven
      generation of specific out-of-equilibrium states, an accepted concept for
      maintenance of transmembrane lipid asymmetry, must also be considered on the
      lateral level. Lateral enzyme-specific out-of-equilibrium organization of lipid
      domains represents a new level of signal transduction from local (nm) to long
      range (microm) scales. The cross-talk between lateral domain structures and
      dipolar electrostatic fields adds new perspectives to the mechanisms of SMase
      mediated signal transduction in biological membranes.

PMID- 15489299
TI  - Thermally induced fibrillar aggregation of hen egg white lysozyme.
AB  - We study the effect of pH and temperature on fibril formation from hen egg white
      lysozyme. Fibril formation is promoted by low pH and temperatures close to the
      midpoint temperature for protein unfolding (detected using far-ultraviolet
      circular dichroism). At the optimal conditions for fibril formation (pH 2.0, T =
      57 degrees C), on-line static light-scattering shows the formation of fibrils
      after a concentration-independent lag time of approximately 48 h. Nucleation
      presumably involves a change in the conformation of individual lysozyme
      molecules. Indeed, long-term circular dichroism measurements at pH 2.0, T = 57
      degrees C show a marked change of the secondary structure of lysozyme molecules
      after approximately 48 h of heating. From atomic force microscopy we find that
      most of the fibrils have a thickness of approximately 4 nm. These fibrils have a
      coiled structure with a periodicity of approximately 30 nm and show
      characteristic defects after every four or five turns.

PMID- 15489300
TI  - Mechanical properties of single myosin molecules probed with the photonic force
      microscope.
AB  - To characterize elastic properties and geometrical parameters of individual,
      whole myosin molecules during their interaction with actin we sparsely adsorbed
      myosin molecules to nanometer-sized microspheres. Thermally driven position
      fluctuations of these microspheres were recorded with the three-dimensional
      detection scheme of the photonic force microscope. Upon binding of single myosin
      molecules to immobilized actin filaments in the absence of ATP, these thermally
      driven position fluctuations of the microspheres change significantly. From three
      dimensional position fluctuations stiffness and geometrical information of the
      tethering molecule can be derived. Axial stiffness was found to be asymmetric,
      approximately 0.04 pN/nm for extension, approximately 0.004 pN/nm for
      compression. Observed stiffness of whole myosin molecules is much less than
      estimated for individual myosin heads in muscle fibers or for single-molecule
      studies on myosin fragments. The stiffness reported here, however, is identical
      to stiffness found in other single-molecule studies with full-length myosin
      suggesting that the source of this low stiffness is located outside the myosin
      head domain. Analysis of geometrical properties of tethering myosin molecules by
      Brownian dynamics computer simulations suggests a linker length of approximately
      130 nm that is divided by a free hinge located approximately 90 nm above the
      substrate. This pivot location coincides with myosin's hinge region. We
      demonstrate the general applicability of thermal fluctuation analysis to
      determine elastic properties and geometrical factors of individual molecules.

PMID- 15489301
TI  - Measurements of DNA lengths remaining in a viral capsid after osmotically
      suppressed partial ejection.
AB  - The effect of external osmotic pressure on the extent of DNA ejection from
      bacteriophage-lambda was recently investigated (Evilevitch et al., 2003). The
      total length of DNA ejected was measured via the 260-nm absorption by free
      nucleotides, after opening of the capsids in the presence of varying amounts of
      polyethylene glycol 8000 and DNase I. As a function of osmolyte concentration,
      this absorption was shown to decrease progressively, ultimately vanishing
      completely for a sufficiently high external osmotic pressure. In this work we
      report the results of both sedimentation and gel analysis of the length of DNA
      remaining inside the capsids, as a function of osmolyte concentration. It is
      confirmed in this way that the progressive inhibition of DNA ejection corresponds
      to partial ejection from all of the capsids.

PMID- 15489302
TI  - A 3-D computational model predicts that cell deformation affects selectin
      mediated leukocyte rolling.
AB  - Leukocyte recruitment to sites of inflammation is initiated by their tethering
      and rolling on the activated endothelium under flow. Even though the fast
      kinetics and high tensile strength of selectin-ligand bonds are primarily
      responsible for leukocyte rolling, experimental evidence suggests that cellular
      properties such as cell deformability and microvillus elasticity actively
      modulate leukocyte rolling behavior. Previous theoretical models either assumed
      cells as rigid spheres or were limited to two-dimensional representations of
      deformable cells with deterministic receptor-ligand kinetics, thereby failing to
      accurately predict leukocyte rolling. We therefore developed a three-dimensional
      computational model based on the immersed boundary method to predict receptor
      mediated rolling of deformable cells in shear flow coupled to a Monte Carlo
      method simulating the stochastic receptor-ligand interactions. Our model predicts
      for the first time that the rolling of more compliant cells is relatively
      smoother and slower compared to cells with stiffer membranes, due to increased
      cell-substrate contact area. At the molecular level, we show that the average
      number of bonds per cell as well as per single microvillus decreases with
      increasing membrane stiffness. Moreover, the average bond lifetime decreases with
      increasing shear rate and with increasing membrane stiffness, due to higher
      hydrodynamic force experienced by the cell. Taken together, our model captures
      the effect of cellular properties on the coupling between hydrodynamic and
      receptor-ligand bond forces, and successfully explains the stable leukocyte
      rolling at a wide range of shear rates over that of rigid microspheres.

PMID- 15489303
TI  - Disentangling ligand migration and heme pocket relaxation in cytochrome P450cam.
AB  - In this work we show that ligand migration and active site conformational
      relaxation can occur independently of each other in hemoproteins. The complicated
      kinetics of carbon monoxide rebinding with cytochrome P450cam display up to five
      distinct processes between 77 K and 300 K. They were disentangled by using a
      combination of three approaches: 1), the competition of the ligand with xenon for
      the occupation of internal protein cavities; 2), the modulation of the amount of
      distal steric hindrance within the heme pocket by varying the nature of the
      substrate; and 3), molecular mechanics calculations to support the proposed heme
      substrate relaxation mechanism and to seek internal cavities. In cytochrome
      P450cam, active site conformational relaxation results from the displacement of
      the substrate toward the heme center upon photodissociation of the ligand. It is
      responsible for the long, puzzling bimodal nature of the rebinding kinetics
      observed down to 77 K. The relaxation rate is strongly substrate-dependent.
      Ligand migration is slower and is observed only above 135 K. Migration and return
      rates are independent of the substrate.

PMID- 15489304
TI  - Micromechanical architecture of the endothelial cell cortex.
AB  - Mechanical properties of living cells are important for cell shape, motility, and
      cellular responses to biochemical and biophysical signals. Although these
      properties are predominantly determined by the cytoskeleton, relatively little is
      known about the mechanical organization of cells at a subcellular level. We have
      studied the cell cortex of bovine pulmonary artery endothelial cells (BPAECs)
      using atomic force microscopy (AFM) and confocal fluorescence microscopy (CFM).
      We show that the contrast in AFM imaging of these cells derives in large part
      from differences in local mechanical properties, and AFM images of BPAEC reveal
      the local micromechanical architecture of their apical cortex at approximately
      125 nm resolution. Mechanically the cortex in these cells is organized as a
      polygonal mesh at two length scales: a coarse mesh with mesh element areas
      approximately 0.5-10 microm2, and a finer mesh with areas <0.5 microm2. These
      meshes appear to be intertwined, which may have interesting implications for the
      mechanical properties of the cell. Correlated AFM-CFM experiments and
      pharmacological treatments reveal that actin and vimentin are components of the
      coarse mesh, but microtubules are not mechanical components of the BPAEC apical
      cortex.

PMID- 15489305
TI  - Extended, relaxed, and condensed conformations of hyaluronan observed by atomic
      force microscopy.
AB  - The conformation of the polysaccharide hyaluronan (HA) has been investigated by
      tapping mode atomic force microscopy in air. HA deposited on a prehydrated mica
      surface favored an extended conformation, attributed to molecular combing and
      inhibition of subsequent chain recoil by adhesion to the structured water layer
      covering the surface. HA deposited on freshly cleaved mica served as a defect in
      a partially structured water layer, and favored relaxed, weakly helical, coiled
      conformations. Intramolecularly condensed forms of HA were also observed, ranging
      from pearl necklace forms to thick rods. The condensation is attributed to weak
      adhesion to the mica surface, counterion-mediated attractive electrostatic
      interactions between polyelectrolytes, and hydration effects. Intermolecular
      association of both extended and condensed forms of HA was observed to result in
      the formation of networks and twisted fibers, in which the chain direction is not
      necessarily parallel to the fiber direction. Whereas the relaxed coil and
      partially condensed conformations of HA are relevant to the native structure of
      liquid connective tissues, fully condensed rods may be more relevant for HA
      tethered to a cell surface or intracellular HA, and fibrous forms may be relevant
      for HA subjected to shear flow in tight intercellular spaces or in protein-HA
      complexes.

PMID- 15489306
TI  - Molecular dynamics simulation of transmembrane polypeptide orientational
      fluctuations.
AB  - The orientation and motion of a model lysine-terminated transmembrane polypeptide
      were investigated by molecular dynamics simulation. Recent 2H NMR studies of
      synthetic polypeptides with deuterated alanine side chains suggest that such
      transmembrane polypeptides undergo fast, axially symmetric reorientation about
      the bilayer normal but have a preferred average azimuthal orientation about the
      helix axis. In this work, interactions that might contribute to this behavior
      were investigated in a simulated system consisting of 64 molecules of 1-palmitoyl
      2-oleoyl-sn-glycero-3-phosphocholine (POPC) and one alpha-helical polypeptide
      with the sequence acetyl-KK-(LA)11-KK-amide. In one simulation, initiated with
      the peptide oriented along the bilayer normal, the system was allowed to evolve
      for 8.5 ns at 1 atm of pressure and a temperature of 55 degrees C. A second
      simulation was initiated with the peptide orientation chosen to match a set of
      experimentally observed alanine methyl deuteron quadrupole splittings and allowed
      to proceed for 10 ns. Simulated alanine methyl group orientations were found to
      be inequivalent, a result that is consistent with 2H NMR observations of
      specifically labeled polypeptides in POPC bilayers. Helix tilt varied
      substantially over the durations of both simulations. In the first simulation,
      the peptide tended toward an orientation about the helix axis similar to that
      suggested by experiment. In the second simulation, orientation about the helix
      axis tended to return to this value after an excursion. These results provide
      some insight into how interactions at the bilayer surface can constrain
      reorientation about the helix axis while accommodating large changes in helix
      tilt.

PMID- 15489307
TI  - Entropy calculation of HIV-1 Env gp120, its receptor CD4, and their complex: an
      analysis of configurational entropy changes upon complexation.
AB  - The HIV-1 gp120/CD4 interaction shows a large, unprecedented entropy/enthalpy
      compensation, with the capacity to fine-tune recognition over a broad range of
      affinity. The intermolecular interaction involves stable hydrophobic contacts
      with a unique protruding CD4-Phe43 structure surrounded by an intermolecular
      hydrogen-bond network that covers the hemisphere of the CD4 D1 domain. We have
      applied a heuristic formula based on the covariance matrix of atom-positional
      fluctuations to assess the configurational entropy of the gp120/CD4 complex at
      different levels. The system was dissected into various subsets of atoms to
      evaluate the entropic contributions of different functional elements. By
      combining the trajectories of the free and complex forms, further insight into
      the conformational sampling was extracted. Despite the limited sampling time of
      10 ns, the theoretically derived changes in configurational entropy are in fair
      agreement with the experimentally determined data. The simultaneous evaluation of
      different interaction modes through a decomposition approach is only feasible
      with the knowledge of the atomic trajectory of the system. The configurational
      entropy analysis in terms of combined trajectories presented here shall
      potentially provide accurate estimations of thermodynamic properties of
      biomolecules given sufficient sampling of conformational space.

PMID- 15489308
TI  - Elucidation and structural analysis of conserved pools for genome-scale metabolic
      reconstructions.
AB  - In this article, we introduce metabolite concentration coupling analysis (MCCA)
      to study conservation relationships for metabolite concentrations in genome-scale
      metabolic networks. The analysis allows the global identification of subsets of
      metabolites whose concentrations are always coupled within common conserved
      pools. Also, the minimal conserved pool identification (MCPI) procedure is
      developed for elucidating conserved pools for targeted metabolites without
      computing the entire basis conservation relationships. The approaches are
      demonstrated on genome-scale metabolic reconstructions of Helicobacter pylori,
      Escherichia coli, and Saccharomyces cerevisiae. Despite significant differences
      in the size and complexity of the examined organism's models, we find that the
      concentrations of nearly all metabolites are coupled within a relatively small
      number of subsets. These correspond to the overall exchange of carbon molecules
      into and out of the networks, interconversion of energy and redox cofactors, and
      the transfer of nitrogen, sulfur, phosphate, coenzyme A, and acyl carrier protein
      moieties among metabolites. The presence of large conserved pools can be viewed
      as global biophysical barriers protecting cellular systems from stresses,
      maintaining coordinated interconversions between key metabolites, and providing
      an additional mode of global metabolic regulation. The developed approaches thus
      provide novel and versatile tools for elucidating coupling relationships between
      metabolite concentrations with implications in biotechnological and medical
      applications.

PMID- 15489309
TI  - Control of glycolytic oscillations by temperature.
AB  - External control of oscillatory glycolysis in yeast extract has been performed by
      application of either homogeneous temperature oscillations or stationary, spatial
      temperature gradients. Entrainment of the glycolytic oscillations by the 1/2- and
      1/3-harmonic, as well as the fundamental input frequency, could be observed. From
      the phase response curve to a single temperature pulse, a distinct sensitivity of
      NADH-oxidizing processes, compared with NAD-reducing processes, is visible.
      Determination of glycolytic intermediates shows that the feedback-regulated
      phosphofructokinase as well as the glyceraldehyde-3-phosphate dehydrogenase are
      the most temperature-sensitive steps of glycolysis. We also find strong
      concentration changes in ATP and AMP at varying temperatures and, accordingly, in
      the energy charge. Construction of a feedback loop for spatial control of
      temperature by means of a Peltier element allowed us to apply a temperature
      gradient to the yeast extract. With this setup it is possible to initiate
      traveling waves and to control the wave velocity.

PMID- 15489310
TI  - Interhelical spacing in liquid crystalline spermine and spermidine-DNA
      precipitates.
AB  - The structure of polyamines-DNA precipitates was studied by x-ray diffraction.
      Precise measurements of the interhelix distance a(H) were obtained at different
      NaCl, polyamine, and DNA concentrations. Most of the results were obtained using
      spermine and few others using spermidine. The precipitates are liquid
      crystalline, either hexagonal and/or cholesteric, with an interhelical spacing
      that depends on the ionic concentrations and on the polyamine type. In our
      experimental conditions, the spacing varies from 28.15 to 33.4 angstroms. This
      variation is interpreted in terms of different ionic components that are present
      inside the precipitates and that are thought to regulate the value of the
      cohesive energy of DNA. These results are discussed in relation to the biological
      processes requiring a closeness of double helices and to the role played by
      polyamine analogs in cancer therapy.

PMID- 15489311
TI  - Cardiac synthesis of aldosterone: going, going, gone...?

PMID- 15489312
TI  - Insulin-like growth factor I: the yin and yang of muscle atrophy.

PMID- 15489313
TI  - Hypophysiotropic thyrotropin-releasing hormone neurons as transducers of energy
      homeostasis.

PMID- 15489314
TI  - Divide and differentiate: ghrelin instructs the Leydig cells.

PMID- 15489315
TI  - Hypoxia and sFlt-1 in preeclampsia: the "chicken-and-egg" question.

PMID- 15489316
TI  - Akt phosphorylation is not sufficient for insulin-like growth factor-stimulated
      myogenin expression but must be accompanied by down-regulation of mitogen
      activated protein kinase/extracellular signal-regulated kinase phosphorylation.
AB  - IGF-I has a unique biphasic effect on skeletal muscle differentiation. Initially,
      IGF-I inhibits expression of myogenin, a skeletal muscle-specific regulatory
      factor essential for myogenesis. Subsequently, IGF-I switches to stimulating
      expression of myogenin. The mechanisms that mediate this switch in IGF action are
      incompletely understood. Several laboratories have demonstrated that the
      phosphatidylinositol-3-kinase/Akt signaling pathway is essential for myogenic
      differentiation and have suggested that this pathway mediates IGF-I stimulation
      of myogenin mRNA expression, an early critical step in the differentiation
      process. These studies, however, did not address concurrent Akt and MAPK/ERK1/2
      phosphorylation, the latter of which is also known to regulate myogenic
      differentiation. In the present study in rat L6E9 muscle cells, we have
      manipulated ERK1/2 phosphorylation with either an upstream inhibitor or activator
      and examined concurrent levels of Akt and ERK1/2 phosphorylation and of myogenin
      mRNA expression in response to treatment with IGF-I. We find that even in the
      presence of phosphorylated Akt, it is only when ERK1/2 phosphorylation is
      inhibited that IGF-I can stimulate myogenin mRNA expression. Thus, although Akt
      phosphorylation may be necessary, it is not sufficient for induction of myogenic
      differentiation by IGF-I and must be accompanied by a decrease in ERK1/2
      phosphorylation.

PMID- 15489317
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 15489318
TI  - ORFeome cloning and systems biology: standardized mass production of the parts
      from the parts-list.
AB  - Together with metabolites, proteins and RNAs form complex biological systems
      through highly intricate networks of physical and functional interactions. Large
      scale studies aimed at a molecular understanding of the structure, function, and
      dynamics of proteins and RNAs in the context of cellular networks require novel
      approaches and technologies. This Special Issue of Genome Research features
      strategies for the high-throughput construction and manipulation of complete sets
      of protein-encoding open reading frames (ORFeome), gene promoters (promoterome),
      and noncoding RNAs, as predicted from genome and transcriptome sequences. Here we
      discuss the use of a recombinational cloning system that allows efficiency,
      adaptability, and compatibility in the generation of ORFeome, promoterome, and
      other resources.

PMID- 15489319
TI  - Academia-industry collaboration: an integral element for building "omic"
      resources.

PMID- 15489320
TI  - The responsibility to share: sharing the responsibility.

PMID- 15489321
TI  - Many paths to many clones: a comparative look at high-throughput cloning methods.
AB  - The creation of genome-scale clone resources is a difficult and costly process,
      making it essential to maximize the efficiency of each step of clone creation. In
      this review, we compare the available commercial and open-source recombinational
      cloning methods with regard to their use in creating comprehensive open reading
      frame (ORF) clone collections with an emphasis on the properties requisite to use
      in a high-throughput setting. The most efficient strategy to the creation of ORF
      clone resources is to build a master clone collection that serves as a quality
      validated source for producing collections of expression clones. We examine the
      methods for recombinational cloning available for both the creation of master
      clones and their conversion into expression clones. Alternative approaches to
      creating clones involving mixing of cloning methods, including gap-repair
      cloning, are also explored.

PMID- 15489322
TI  - From ORFeomes to protein interaction maps in viruses.
AB  - Although cloned viral ORFeomes are particularly well suited for genome-wide
      interaction mapping due to the limited size of viral genomes, only a few such
      studies have been published. Here, we summarize virus interaction mapping
      projects involving vaccinia virus, hepatitis C virus (HCV), potato virus A (PVA),
      pea seed-borne mosaic virus (PSbMV), and bacteriophage T7, as well as some
      projects in progress. The studies reported suggest that virus-specific coding and
      replication strategies must be taken into account to yield accurate numbers of
      protein interactions. In particular, the number of false negatives can be
      significant for RNA viruses expressing precursor polyproteins (because
      interactions between full-length mature proteins are often not detected due to
      incorrect processing) and for viruses replicating in the cytoplasm whose
      transcripts have not been selected for splicing signals. In conclusion, the
      studies on viral protein interaction maps suggest that cloned pathogen ORFeomes
      will contribute to a holistic picture of the pathogenesis of infectious diseases
      and are ideal starting points for new approaches in systems biology. Both viral
      ORFeome and interaction mapping projects are being documented on our Web site
      (http://itgmv1.fzk.de/www/itg/uetz/virus/).

PMID- 15489323
TI  - Analysis of human mRNAs with the reference genome sequence reveals potential
      errors, polymorphisms, and RNA editing.
AB  - The NCBI Reference Sequence (RefSeq) project and the NIH Mammalian Gene
      Collection (MGC) together define a set of approximately 30,000 nonredundant human
      mRNA sequences with identified coding regions representing 17,000 distinct loci.
      These high-quality mRNA sequences allow for the identification of transcribed
      regions in the human genome sequence, and many researchers accept them as the
      correct representation of each defined gene sequence. Computational comparison of
      these mRNA sequences and the recently published essentially finished human genome
      sequence reveals several thousand undocumented nonsynonymous substitution and
      frame shift discrepancies between the two resources. Additional analysis is
      undertaken to verify that the euchromatic human genome is sufficiently complete-
      containing nearly the whole mRNA collection, thus allowing for a comprehensive
      analysis to be undertaken. Many of the discrepancies will prove to be genuine
      polymorphisms in the human population, somatic cell genomic variants, or examples
      of RNA editing. It is observed that the genome sequence variant has significant
      additional support from other mRNAs and ESTs, almost four times more often than
      does the mRNA variant, suggesting that the genome sequence is more accurate. In
      approximately 15% of these cases, there is substantial support for both variants,
      suggestive of an undocumented polymorphism. An initial screening against a 24
      individual genomic DNA diversity panel verified 60% of a small set of potential
      single nucleotide polymorphisms from which successful results could be obtained.
      We also find statistical evidence that a few of these discrepancies are due to
      RNA editing. Overall, these results suggest that the mRNA collections may contain
      a substantial number of errors. For current and future mRNA collections, it may
      be prudent to fully reconcile each genome sequence discrepancy, classifying each
      as a polymorphism, site of RNA editing or somatic cell variation, or genome
      sequence error.

PMID- 15489324
TI  - An ORFeome-based analysis of human transcription factor genes and the
      construction of a microarray to interrogate their expression.
AB  - Transcription factors (TFs) are essential regulators of gene expression, and
      mutated TF genes have been shown to cause numerous human genetic diseases. Yet to
      date, no single, comprehensive database of human TFs exists. In this work, we
      describe the collection of an essentially complete set of TF genes from one
      depiction of the human ORFeome, and the design of a microarray to interrogate
      their expression. Taking 1468 known TFs from TRANSFAC, InterPro, and FlyBase, we
      used this seed set to search the ScriptSure human transcriptome database for
      additional genes. ScriptSure's genome-anchored transcript clusters allowed us to
      work with a nonredundant high-quality representation of the human transcriptome.
      We used a high-stringency similarity search by using BLASTN, and a protein motif
      search of the human ORFeome by using hidden Markov models of DNA-binding domains
      known to occur exclusively or primarily in TFs. Four hundred ninety-four
      additional TF genes were identified in the overlap between the two searches,
      bringing our estimate of the total number of human TFs to 1962. Zinc finger genes
      are by far the most abundant family (762 members), followed by homeobox (199
      members) and basic helix-loop-helix genes (117 members). We designed a microarray
      of 50-mer oligonucleotide probes targeted to a unique region of the coding
      sequence of each gene. We have successfully used this microarray to interrogate
      TF gene expression in species as diverse as chickens and mice, as well as in
      humans.

PMID- 15489325
TI  - Analysis of small human proteins reveals the translation of upstream open reading
      frames of mRNAs.
AB  - To find novel short coding sequences from accumulated full-length cDNA sequences,
      proteomic analysis of small proteins expressed in human leukemia K562 cells was
      performed using high-resolution nanoflow liquid chromatography coupled with
      electrospray ionization tandem mass spectrometry. Our analysis led to the
      identification of 54 proteins not more than 100 amino acids in length, including
      four novel ones. These novel short coding sequences were all located upstream of
      the longest open reading frame (ORF) of the corresponding cDNA. Our findings
      indicate that the translation of short ORFs occurs in vivo whether or not there
      exists a longer coding region in the downstream of the mRNA. This investigation
      provides the first direct evidence of translation of upstream ORFs in human
      cells, which could greatly change the current outline of the human proteome.

PMID- 15489326
TI  - 1274 full-open reading frames of transcripts expressed in the developing mouse
      nervous system.
AB  - As part of the trans-National Institutes of Health (NIH) Mouse Brain Molecular
      Anatomy Project (BMAP), and in close coordination with the NIH Mammalian Gene
      Collection Program (MGC), we initiated a large-scale project to clone, identify,
      and sequence the complete open reading frame (ORF) of transcripts expressed in
      the developing mouse nervous system. Here we report the analysis of the ORF
      sequence of 1274 cDNAs, obtained from 47 full-length-enriched cDNA libraries,
      constructed by using a novel approach, herein described. cDNA libraries were
      derived from size-fractionated cytoplasmic mRNA isolated from brain and eye
      tissues obtained at several embryonic stages and postnatal days. Altogether,
      including the full-ORF MGC sequences derived from these libraries by the MGC
      sequencing team, NIH_BMAP full-ORF sequences correspond to approximately 20% of
      all transcripts currently represented in mouse MGC. We show that NIH_BMAP clones
      comprise 68% of mouse MGC cDNAs > or =5 kb, and 54% of those > or =4 kb, as of
      March 15, 2004. Importantly, we identified transcripts, among the 1274 full-ORF
      sequences, that are exclusively or predominantly expressed in brain and eye
      tissues, many of which encode yet uncharacterized proteins.

PMID- 15489327
TI  - C. elegans ORFeome version 3.1: increasing the coverage of ORFeome resources with
      improved gene predictions.
AB  - The first version of the Caenorhabditis elegans ORFeome cloning project, based on
      release WS9 of Wormbase (August 1999), provided experimental verifications for
      approximately 55% of predicted protein-encoding open reading frames (ORFs). The
      remaining 45% of predicted ORFs could not be cloned, possibly as a result of
      mispredicted gene boundaries. Since the release of WS9, gene predictions have
      improved continuously. To test the accuracy of evolving predictions, we attempted
      to PCR-amplify from a highly representative worm cDNA library and Gateway-clone
      approximately 4200 ORFs missed earlier and for which new predictions are
      available in WS100 (May 2003). In this set we successfully cloned 63% of ORFs
      with supporting experimental data ("touched" ORFs), and 42% of ORFs with no
      supporting experimental evidence ("untouched" ORFs). Approximately 2000 full
      length ORFs were cloned in-frame, 13% of which were corrected in their
      exon/intron structure relative to WS100 predictions. In total, approximately
      12,500 C. elegans ORFs are now available as Gateway Entry clones for various
      reverse proteomics (ORFeome v3.1). This work illustrates why the cloning of a
      complete C. elegans ORFeome, and likely the ORFeomes of other multicellular
      organisms, needs to be an iterative process that requires multiple rounds of
      experimental validation together with gradually improving gene predictions.

PMID- 15489328
TI  - Feasibility of genome-scale construction of promoter::reporter gene fusions for
      expression in Caenorhabditis elegans using a multisite gateway recombination
      system.
AB  - The understanding of gene function increasingly requires the characterization of
      DNA segments containing promoters and their associated regulatory sequences. We
      describe a novel approach for linking multiple DNA segments, here applied to the
      generation of promoter::reporter fusions. Promoters from Caenorhabditis elegans
      genes were cloned using the MultiSite Gateway cloning technology. The capacity
      for using this system for efficient construction of chimeric genes was explored
      by constructing promoter::reporter gene fusions with a gfp reporter. The
      promoters were found to provide appropriate expression of GFP upon introduction
      into C. elegans, demonstrating that the short Gateway recombination site between
      the promoter and the reporter did not interfere with transcription or
      translation. The recombinational cloning involved in the Gateway system, which
      permits the highly efficient and precise transfer of DNA segments between plasmid
      vectors, makes this technology ideal for genomics research programs.

PMID- 15489329
TI  - High-throughput generation of P. falciparum functional molecules by
      recombinational cloning.
AB  - Large-scale functional genomics studies for malaria vaccine and drug development
      will depend on the generation of molecular tools to study protein expression. We
      examined the feasibility of a high-throughput cloning approach using the Gateway
      system to create a large set of expression clones encoding Plasmodium falciparum
      single-exon genes. Master clones and their ORFs were transferred en masse to
      multiple expression vectors. Target genes (n = 303) were selected using specific
      sets of criteria, including stage expression and secondary structure. Upon
      screening four colonies per capture reaction, we achieved 84% cloning efficiency.
      The genes were subcloned in parallel into three expression vectors: a DNA vaccine
      vector and two protein expression vectors. These transfers yielded a 100% success
      rate without any observed recombination based on single colony screening. The
      functional expression of 95 genes was evaluated in mice with DNA vaccine
      constructs to generate antibody against various stages of the parasite. From
      these, 19 induced antibody titers against the erythrocytic stages and three
      against sporozoite stages. We have overcome the potential limitation of producing
      large P. falciparum clone sets in multiple expression vectors. This approach
      represents a powerful technique for the production of molecular reagents for
      genome-wide functional analysis of the P. falciparum genome and will provide for
      a resource for the malaria resource community distributed through public
      repositories.

PMID- 15489330
TI  - Systematic recovery and analysis of full-ORF human cDNA clones.
AB  - The Mammalian Gene Collection (MGC) consortium (http://mgc.nci.nih.gov) seeks to
      establish publicly available collections of full-ORF cDNAs for several organisms
      of significance to biomedical research, including human. To date over 15,200
      human cDNA clones containing full-length open reading frames (ORFs) have been
      identified via systematic expressed sequence tag (EST) analysis of a diverse set
      of cDNA libraries; however, further systematic EST analysis is no longer an
      efficient method for identifying new cDNAs. As part of our involvement in the MGC
      program, we have developed a scalable method for targeted recovery of cDNA clones
      to facilitate recovery of genes absent from the MGC collection. First, cDNA is
      synthesized from various RNAs, followed by polymerase chain reaction (PCR)
      amplification of transcripts in 96-well plates using gene-specific primer pairs
      flanking the ORFs. Amplicons are cloned into a sequencing vector, and full-length
      sequences are obtained. Sequences are processed and assembled using Phred and
      Phrap, and analyzed using Consed and a number of bioinformatics methods we have
      developed. Sequences are compared with the Reference Sequence (RefSeq) database,
      and validation of sequence discrepancies is attempted using other sequence
      databases including dbEST and dbSNP. Clones with identical sequence to RefSeq or
      containing only validated changes will become part of the MGC human gene
      collection. Clones containing novel splice variants or polymorphisms have also
      been identified. Our approach to clone recovery, applied at large scale, has the
      potential to recover many and possibly most of the genes absent from the MGC
      collection.

PMID- 15489331
TI  - A gateway-compatible yeast one-hybrid system.
AB  - Since the advent of microarrays, vast amounts of gene expression data have been
      generated. However, these microarray data fail to reveal the transcription
      regulatory mechanisms that underlie differential gene expression, because the
      identity of the responsible transcription factors (TFs) often cannot be directly
      inferred from such data sets. Regulatory TFs activate or repress transcription of
      their target genes by binding to cis-regulatory elements that are frequently
      located in a gene's promoter. To understand the mechanisms underlying
      differential gene expression, it is necessary to identify physical interactions
      between regulatory TFs and their target genes. We developed a Gateway-compatible
      yeast one-hybrid (Y1H) system that enables the rapid, large-scale identification
      of protein-DNA interactions using both small (i.e., DNA elements of interest) and
      large (i.e., gene promoters) DNA fragments. We used four well-characterized
      Caenorhabditis elegans promoters as DNA baits to test the functionality of this
      Y1H system. We could detect approximately 40% of previously reported TF-promoter
      interactions. By performing screens using two complementary libraries, we found
      novel potentially interacting TFs for each promoter. We recapitulated several of
      the Y1H-based protein-DNA interactions using luciferase reporter assays in
      mammalian cells. Taken together, the Gateway-compatible Y1H system will allow the
      high-throughput identification of protein-DNA interactions and may be a valuable
      tool to decipher transcription regulatory networks.

PMID- 15489332
TI  - High-throughput expression of C. elegans proteins.
AB  - Proteome-scale studies of protein three-dimensional structures should provide
      valuable information for both investigating basic biology and developing
      therapeutics. Critical for these endeavors is the expression of recombinant
      proteins. We selected Caenorhabditis elegans as our model organism in a
      structural proteomics initiative because of the high quality of its genome
      sequence and the availability of its ORFeome, protein-encoding open reading
      frames (ORFs), in a flexible recombinational cloning format. We developed a
      robotic pipeline for recombinant protein expression, applying the Gateway
      cloning/expression technology and utilizing a stepwise automation strategy on an
      integrated robotic platform. Using the pipeline, we have carried out heterologous
      protein expression experiments on 10,167 ORFs of C. elegans. With one expression
      vector and one Escherichia coli strain, protein expression was observed for 4854
      ORFs, and 1536 were soluble. Bioinformatics analysis of the data indicates that
      protein hydrophobicity is a key determining factor for an ORF to yield a soluble
      expression product. This protein expression effort has investigated the largest
      number of genes in any organism to date. The pipeline described here is
      applicable to high-throughput expression of recombinant proteins for other
      species, both prokaryotic and eukaryotic, provided that ORFeome resources become
      available.

PMID- 15489333
TI  - Concerted assembly and cloning of multiple DNA segments using in vitro site
      specific recombination: functional analysis of multi-segment expression clones.
AB  - The ability to clone and manipulate DNA segments is central to molecular methods
      that enable expression, screening, and functional characterization of genes,
      proteins, and regulatory elements. We previously described the development of a
      novel technology that utilizes in vitro site-specific recombination to provide a
      robust and flexible platform for high-throughput cloning and transfer of DNA
      segments. By using an expanded repertoire of recombination sites with unique
      specificities, we have extended the technology to enable the high-efficiency in
      vitro assembly and concerted cloning of multiple DNA segments into a vector
      backbone in a predefined order, orientation, and reading frame. The efficiency
      and flexibility of this approach enables collections of functional elements to be
      generated and mixed in a combinatorial fashion for the parallel assembly of
      numerous multi-segment constructs. The assembled constructs can be further
      manipulated by directing exchange of defined segments with alternate DNA
      segments. In this report, we demonstrate feasibility of the technology and
      application to the generation of fusion proteins, the linkage of promoters to
      genes, and the assembly of multiple protein domains. The technology has broad
      implications for cell and protein engineering, the expression of multidomain
      proteins, and gene function analysis.

PMID- 15489335
TI  - Human ORFeome version 1.1: a platform for reverse proteomics.
AB  - The advent of systems biology necessitates the cloning of nearly entire sets of
      protein-encoding open reading frames (ORFs), or ORFeomes, to allow functional
      studies of the corresponding proteomes. Here, we describe the generation of a
      first version of the human ORFeome using a newly improved Gateway recombinational
      cloning approach. Using the Mammalian Gene Collection (MGC) resource as a
      starting point, we report the successful cloning of 8076 human ORFs, representing
      at least 7263 human genes, as mini-pools of PCR-amplified products. These were
      assembled into the human ORFeome version 1.1 (hORFeome v1.1) collection. After
      assessing the overall quality of this version, we describe the use of hORFeome
      v1.1 for heterologous protein expression in two different expression systems at
      proteome scale. The hORFeome v1.1 represents a central resource for the cloning
      of large sets of human ORFs in various settings for functional proteomics of many
      types, and will serve as the foundation for subsequent improved versions of the
      human ORFeome.

PMID- 15489334
TI  - The status, quality, and expansion of the NIH full-length cDNA project: the
      Mammalian Gene Collection (MGC).
AB  - The National Institutes of Health's Mammalian Gene Collection (MGC) project was
      designed to generate and sequence a publicly accessible cDNA resource containing
      a complete open reading frame (ORF) for every human and mouse gene. The project
      initially used a random strategy to select clones from a large number of cDNA
      libraries from diverse tissues. Candidate clones were chosen based on 5'-EST
      sequences, and then fully sequenced to high accuracy and analyzed by algorithms
      developed for this project. Currently, more than 11,000 human and 10,000 mouse
      genes are represented in MGC by at least one clone with a full ORF. The random
      selection approach is now reaching a saturation point, and a transition to
      protocols targeted at the missing transcripts is now required to complete the
      mouse and human collections. Comparison of the sequence of the MGC clones to
      reference genome sequences reveals that most cDNA clones are of very high
      sequence quality, although it is likely that some cDNAs may carry missense
      variants as a consequence of experimental artifact, such as PCR, cloning, or
      reverse transcriptase errors. Recently, a rat cDNA component was added to the
      project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were
      expanded to take advantage of the high-throughput MGC pipeline.

PMID- 15489336
TI  - From ORFeome to biology: a functional genomics pipeline.
AB  - As several model genomes have been sequenced, the elucidation of protein function
      is the next challenge toward the understanding of biological processes in health
      and disease. We have generated a human ORFeome resource and established a
      functional genomics and proteomics analysis pipeline to address the major topics
      in the post-genome-sequencing era: the identification of human genes and splice
      forms, and the determination of protein localization, activity, and interaction.
      Combined with the understanding of when and where gene products are expressed in
      normal and diseased conditions, we create information that is essential for
      understanding the interplay of genes and proteins in the complex biological
      network. We have implemented bioinformatics tools and databases that are suitable
      to store, analyze, and integrate the different types of data from high-throughput
      experiments and to include further annotation that is based on external
      information. All information is presented in a Web database
      (http://www.dkfz.de/LIFEdb). It is exploited for the identification of disease
      relevant genes and proteins for diagnosis and therapy.

PMID- 15489337
TI  - High-throughput computational and experimental techniques in structural genomics.
AB  - Structural genomics has as its goal the provision of structural information for
      all possible ORF sequences through a combination of experimental and
      computational approaches. The access to genome sequences and cloning resources
      from an ever-widening array of organisms is driving high-throughput structural
      studies by the New York Structural Genomics Research Consortium. In this report,
      we outline the progress of the Consortium in establishing its pipeline for
      structural genomics, and some of the experimental and bioinformatics efforts
      leading to structural annotation of proteins. The Consortium has established a
      pipeline for structural biology studies, automated modeling of ORF sequences
      using solved (template) structures, and a novel high-throughput approach
      (metallomics) to examining the metal binding to purified protein targets. The
      Consortium has so far produced 493 purified proteins from >1077 expression
      vectors. A total of 95 have resulted in crystal structures, and 81 are deposited
      in the Protein Data Bank (PDB). Comparative modeling of these structures has
      generated >40,000 structural models. We also initiated a high-throughput metal
      analysis of the purified proteins; this has determined that 10%-15% of the
      targets contain a stoichiometric structural or catalytic transition metal atom.
      The progress of the structural genomics centers in the U.S. and around the world
      suggests that the goal of providing useful structural information on most all ORF
      domains will be realized. This projected resource will provide structural biology
      information important to understanding the function of most proteins of the cell.

PMID- 15489338
TI  - WormBase as an integrated platform for the C. elegans ORFeome.
AB  - The ORFeome project has validated and corrected a large number of predicted gene
      models in the nematode C. elegans, and has provided an enormous resource for
      proteome-scale studies. To make the resource useful to the research and teaching
      community, it needs to be integrated with other large-scale data sets, including
      the C. elegans genome, cell lineage, neurological wiring diagram, transcriptome,
      and gene expression map. This integration is also critical because the ORFeome
      data sets, like other 'omics' data sets, have significant false-positive and
      false-negative rates, and comparison to related data is necessary to make
      confidence judgments in any given data point. WormBase, the central data
      repository for information about C. elegans and related nematodes, provides such
      a platform for integration. In this report, we will describe how C. elegans
      ORFeome data are deposited in the database, how they are used to correct gene
      models, how they are integrated and displayed in the context of other data sets
      at the WormBase Web site, and how WormBase establishes connection with the
      reagent-based resources at the ORFeome project Web site.

PMID- 15489339
TI  - Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based
      RNAi library.
AB  - The recently completed Caenorhabditis elegans genome sequence allows application
      of high-throughput (HT) approaches for phenotypic analyses using RNA interference
      (RNAi). As large phenotypic data sets become available, "phenoclustering"
      strategies can be used to begin understanding the complex molecular networks
      involved in development and other biological processes. The current HT-RNAi
      resources represent a great asset for phenotypic profiling but are limited by
      lack of flexibility. For instance, existing resources do not take advantage of
      the latest improvements in RNAi technology, such as inducible hairpin RNAi. Here
      we show that a C. elegans ORFeome resource, generated with the Gateway cloning
      system, can be used as a starting point to generate alternative HT-RNAi resources
      with enhanced flexibility. The versatility inherent to the Gateway system
      suggests that additional HT-RNAi libraries can now be readily generated to
      perform gene knockdowns under various conditions, increasing the possibilities
      for phenome mapping in C. elegans.

PMID- 15489340
TI  - A first version of the Caenorhabditis elegans Promoterome.
AB  - An important aspect of the development of systems biology approaches in metazoans
      is the characterization of expression patterns of nearly all genes predicted from
      genome sequences. Such "localizome" maps should provide information on where (in
      what cells or tissues) and when (at what stage of development or under what
      conditions) genes are expressed. They should also indicate in what cellular
      compartments the corresponding proteins are localized. Caenorhabditis elegans is
      particularly suited for the development of a localizome map since all its 959
      adult somatic cells can be visualized by microscopy, and its cell lineage has
      been completely described. Here we address one of the challenges of C. elegans
      localizome mapping projects: that of obtaining a genome-wide resource of C.
      elegans promoters needed to generate transgenic animals expressing localization
      markers such as the green fluorescent protein (GFP). To ensure high flexibility
      for future uses, we utilized the newly developed MultiSite Gateway system. We
      generated and validated "version 1.1" of the Promoterome: a resource of
      approximately 6000 C. elegans promoters. These promoters can be transferred
      easily into various Gateway Destination vectors to drive expression of markers
      such as GFP, alone (promoter::GFP constructs), or in fusion with protein-encoding
      open reading frames available in ORFeome resources (promoter::ORF::GFP).

PMID- 15489341
TI  - Versatile gene-specific sequence tags for Arabidopsis functional genomics:
      transcript profiling and reverse genetics applications.
AB  - Microarray transcript profiling and RNA interference are two new technologies
      crucial for large-scale gene function studies in multicellular eukaryotes. Both
      rely on sequence-specific hybridization between complementary nucleic acid
      strands, inciting us to create a collection of gene-specific sequence tags (GSTs)
      representing at least 21,500 Arabidopsis genes and which are compatible with both
      approaches. The GSTs were carefully selected to ensure that each of them shared
      no significant similarity with any other region in the Arabidopsis genome. They
      were synthesized by PCR amplification from genomic DNA. Spotted microarrays
      fabricated from the GSTs show good dynamic range, specificity, and sensitivity in
      transcript profiling experiments. The GSTs have also been transferred to
      bacterial plasmid vectors via recombinational cloning protocols. These cloned
      GSTs constitute the ideal starting point for a variety of functional approaches,
      including reverse genetics. We have subcloned GSTs on a large scale into vectors
      designed for gene silencing in plant cells. We show that in planta expression of
      GST hairpin RNA results in the expected phenotypes in silenced Arabidopsis lines.
      These versatile GST resources provide novel and powerful tools for functional
      genomics.

PMID- 15489342
TI  - The Pseudomonas aeruginosa PA01 gene collection.
AB  - Pseudomonas aeruginosa, a common inhabitant of soil and water, is an
      opportunistic pathogen of growing clinical relevance. Its genome, one of the
      largest among bacteria [5570 open reading frames (ORFs)] approaches that of
      simple eukaryotes. We have constructed a comprehensive gene collection for this
      organism utilizing the annotated genome of P. aeruginosa PA01 and a highly
      automated and laboratory information management system (LIMS)-supported
      production line. All the individual ORFs have been successfully PCR-amplified and
      cloned into a recombination-based cloning system. We have isolated and archived
      four independent isolates of each individual ORF. Full sequence analysis of the
      first isolate for one-third of the ORFs in the collection has been completed. We
      used two sets of genes from this repository for high-throughput expression and
      purification of recombinant proteins in different systems. The purified proteins
      have been used to set up biochemical and immunological assays directed towards
      characterization of histidine kinases and identification of bacterial proteins
      involved in the immune response of cystic fibrosis patients. This gene repository
      provides a powerful tool for proteome- and genome-scale research of this
      organism, and the strategies adopted to generate this repository serve as a model
      for building clone sets for other bacteria.

PMID- 15489343
TI  - Generation of the Brucella melitensis ORFeome version 1.1.
AB  - The bacteria of the Brucella genus are responsible for a worldwide zoonosis
      called brucellosis. They belong to the alpha-proteobacteria group, as many other
      bacteria that live in close association with a eukaryotic host. Importantly, the
      Brucellae are mainly intracellular pathogens, and the molecular mechanisms of
      their virulence are still poorly understood. Using the complete genome sequence
      of Brucella melitensis, we generated a database of protein-coding open reading
      frames (ORFs) and constructed an ORFeome library of 3091 Gateway Entry clones,
      each containing a defined ORF. This first version of the Brucella ORFeome (v1.1)
      provides the coding sequences in a user-friendly format amenable to high
      throughput functional genomic and proteomic experiments, as the ORFs are
      conveniently transferable from the Entry clones to various Expression vectors by
      recombinational cloning. The cloning of the Brucella ORFeome v1.1 should help to
      provide a better understanding of the molecular mechanisms of virulence,
      including the identification of bacterial protein-protein interactions, but also
      interactions between bacterial effectors and their host's targets.

PMID- 15489346
TI  - Impact of malaria during pregnancy on low birth weight in sub-Saharan Africa.
AB  - Malaria during pregnancy can result in low birth weight (LBW), an important risk
      factor for infant mortality. This article reviews the pathological effects of
      malaria during pregnancy and the implications for the newborn's development and
      survival. Empirical data from throughout Africa on associations between placental
      malaria and birth weight outcome, birth weight outcome and infant mortality, and
      the rates of LBW in areas with various levels of malaria transmission are
      evaluated to assess the increased risks of LBW and infant mortality associated
      with malaria. It is estimated that in areas where malaria is endemic, around 19%
      of infant LBWs are due to malaria and 6% of infant deaths are due to LBW caused
      by malaria. These estimates imply that around 100,000 infant deaths each year
      could be due to LBW caused by malaria during pregnancy in areas of malaria
      endemicity in Africa.

PMID- 15489344
TI  - Mycoplasma pneumoniae and its role as a human pathogen.
AB  - Mycoplasma pneumoniae is a unique bacterium that does not always receive the
      attention it merits considering the number of illnesses it causes and the degree
      of morbidity associated with it in both children and adults. Serious infections
      requiring hospitalization, while rare, occur in both adults and children and may
      involve multiple organ systems. The severity of disease appears to be related to
      the degree to which the host immune response reacts to the infection.
      Extrapulmonary complications involving all of the major organ systems can occur
      in association with M. pneumoniae infection as a result of direct invasion and/or
      autoimmune response. The extrapulmonary manifestations are sometimes of greater
      severity and clinical importance than the primary respiratory infection. Evidence
      for this organism's contributory role in chronic lung conditions such as asthma
      is accumulating. Effective management of M. pneumoniae infections can usually be
      achieved with macrolides, tetracyclines, or fluoroquinolones. As more is learned
      about the pathogenesis and immune response elicited by M. pneumoniae, improvement
      in methods for diagnosis and prevention of disease due to this organism may
      occur.

PMID- 15489347
TI  - Prevention of infection due to Pneumocystis spp. in human immunodeficiency virus
      negative immunocompromised patients.
AB  - Pneumocystis infection in humans was originally described in 1942. The organism
      was initially thought to be a protozoan, but more recent data suggest that it is
      more closely related to the fungi. Patients with cellular immune deficiencies are
      at risk for the development of symptomatic Pneumocystis infection. Populations at
      risk also include patients with hematologic and nonhematologic malignancies,
      hematopoietic stem cell transplant recipients, solid-organ recipients, and
      patients receiving immunosuppressive therapies for connective tissue disorders
      and vasculitides. Trimethoprim-sulfamethoxazole is the agent of choice for
      prophylaxis against Pneumocystis unless a clear contraindication is identified.
      Other options include pentamidine, dapsone, dapsone-pyrimethamine, and
      atovaquone. The risk for PCP varies based on individual immune defects, regional
      differences, and immunosuppressive regimens. Prophylactic strategies must be
      linked to an ongoing assessment of the patient's risk for disease.

PMID- 15489348
TI  - Treatment of infections caused by metronidazole-resistant Trichomonas vaginalis.
AB  - Infections with the sexually transmitted protozoan Trichomonas vaginalis are
      usually treated with metronidazole, a 5-nitroimidazole drug derived from the
      antibiotic azomycin. Metronidazole treatment is generally efficient in
      eliminating T. vaginalis infection and has a low risk of serious side effects.
      However, studies have shown that at least 5% of clinical cases of trichomoniasis
      are caused by parasites resistant to the drug. The lack of approved alternative
      therapies for T. vaginalis treatment means that higher and sometimes toxic doses
      of metronidazole are the only option for patients with resistant disease.
      Clearly, studies of the treatment and prevention of refractory trichomoniasis are
      essential. This review describes the mechanisms of metronidazole resistance in T.
      vaginalis and provides a summary of trichomonicidal and vaccine candidate drugs.

PMID- 15489345
TI  - Immunopathogenesis of oropharyngeal candidiasis in human immunodeficiency virus
      infection.
AB  - Oropharyngeal and esophageal candidiases remain significant causes of morbidity
      in human immunodeficiency virus (HIV)-infected patients, despite the dramatic
      ability of antiretroviral therapy to reconstitute immunity. Notable advances have
      been achieved in understanding, at the molecular level, the relationships between
      the progression of HIV infection, the acquisition, maintenance, and clonality of
      oral candidal populations, and the emergence of antifungal resistance. However,
      the critical immunological defects which are responsible for the onset and
      maintenance of mucosal candidiasis in patients with HIV infection have not been
      elucidated. The devastating impact of HIV infection on mucosal Langerhans' cell
      and CD4(+) cell populations is most probably central to the pathogenesis of
      mucosal candidiasis in HIV-infected patients. However, these defects may be
      partly compensated by preserved host defense mechanisms (calprotectin,
      keratinocytes, CD8(+) T cells, and phagocytes) which, individually or together,
      may limit Candida albicans proliferation to the superficial mucosa. The
      availability of CD4C/HIV transgenic mice expressing HIV-1 in immune cells has
      provided the opportunity to devise a novel model of mucosal candidiasis that
      closely mimics the clinical and pathological features of candidal infection in
      human HIV infection. These transgenic mice allow, for the first time, a precise
      cause-and-effect analysis of the immunopathogenesis of mucosal candidiasis in HIV
      infection under controlled conditions in a small laboratory animal.

PMID- 15489349
TI  - Trichomoniasis.
AB  - Trichomoniasis is perhaps the most common curable sexually transmitted disease
      worldwide, yet few resources are devoted to its control. It is associated with
      potentially serious complications such as preterm birth and human
      immunodeficiency virus acquisition and transmission. The immunology of a related
      organism, Tritrichomonas foetus, which causes disease in cattle, has been
      investigated to some extent, but more work is needed for the human strain,
      Trichomonas vaginalis. In addition, although trichomoniasis is easily treated
      with oral metronidazole, there is concern that the number of strains resistant to
      this antibiotic are increasing, and currently no alternative is licensed in the
      United States. As more is appreciated concerning the important public health
      implications of this common infection, more work will need to be done in
      understanding the diagnosis, treatment, and immunology of this organism.

PMID- 15489351
TI  - Impact of 16S rRNA gene sequence analysis for identification of bacteria on
      clinical microbiology and infectious diseases.
AB  - The traditional identification of bacteria on the basis of phenotypic
      characteristics is generally not as accurate as identification based on genotypic
      methods. Comparison of the bacterial 16S rRNA gene sequence has emerged as a
      preferred genetic technique. 16S rRNA gene sequence analysis can better identify
      poorly described, rarely isolated, or phenotypically aberrant strains, can be
      routinely used for identification of mycobacteria, and can lead to the
      recognition of novel pathogens and noncultured bacteria. Problems remain in that
      the sequences in some databases are not accurate, there is no consensus
      quantitative definition of genus or species based on 16S rRNA gene sequence data,
      the proliferation of species names based on minimal genetic and phenotypic
      differences raises communication difficulties, and microheterogeneity in 16S rRNA
      gene sequence within a species is common. Despite its accuracy, 16S rRNA gene
      sequence analysis lacks widespread use beyond the large and reference
      laboratories because of technical and cost considerations. Thus, a future
      challenge is to translate information from 16S rRNA gene sequencing into
      convenient biochemical testing schemes, making the accuracy of the genotypic
      identification available to the smaller and routine clinical microbiology
      laboratories.

PMID- 15489350
TI  - Coccidioidomycosis: host response and vaccine development.
AB  - Coccidioidomycosis is caused by the dimorphic fungi in the genus Coccidioides.
      These fungi live as mycelia in the soil of desert areas of the American
      Southwest, and when the infectious spores, the arthroconidia, are inhaled, they
      convert into the parasitic spherule/endospore phase. Most infections are mild,
      but these organisms are frank pathogens and can cause severe lethal disease in
      fully immunocompetent individuals. While there is increased risk of disseminated
      disease in certain racial groups and immunocompromised persons, the fact that
      there are hosts who contain the initial infection and exhibit long-term immunity
      to reinfection supports the hypothesis that a vaccine against these pathogens is
      feasible. Multiple studies have shown that protective immunity against primary
      disease is associated with T-helper 1 (Th-1)-associated immune responses. The
      single best vaccine in animal models, formalin-killed spherules (FKS), was tested
      in a human trial but was not found to be significantly protective. This result
      has prompted studies to better define immunodominant Coccidioides antigen with
      the thought that a subunit vaccine would be protective. These efforts have
      defined multiple candidates, but the single best individual immunogen is the
      protein termed antigen 2/proline-rich antigen (Ag2/PRA). Studies in multiple
      laboratories have shown that Ag2/PRA as both protein and genetic vaccines
      provides significant protection against mice challenged systemically with
      Coccidioides. Unfortunately, compared to the FKS vaccine, it is significantly
      less protective as measured by both assays of reduction in fungal CFU and assays
      of survival. The capacity of Ag2/PRA to induce only partial protection was
      emphasized when animals were challenged intranasally. Thus, there is a need to
      define new candidates to create a multivalent vaccine to increase the
      effectiveness of Ag2/PRA. Efforts of genomic screening using expression library
      immunization or bioinformatic approaches to identify new candidates have revealed
      at least two new protective proteins, expression library immunization antigen 1
      (ELI-Ag1) and a beta-1,3-glucanosyltransferase (GEL-1). In addition, previously
      discovered antigens such as Coccidioides-specific antigen (CSA) should be
      evaluated in assays of protection. While studies have yet to be completed with
      combinations of the current candidates, the hypothesis is that with increased
      numbers of candidates in a multivalent vaccine, there will be increased
      protection. As the genome sequences of the two Coccidioides strains which are
      under way are completed and annotated, the effort to find new candidates can
      increase to provide a complete genomic scan for immunodominant proteins. Thus,
      much progress has been made in the discovery of subunit vaccine candidates
      against Coccidioides and there are several candidates showing modest levels of
      protection, but for complete protection against pulmonary challenge we need to
      continue the search for additional candidates.

PMID- 15489353
TI  - Sarcocystis spp. in human infections.
AB  - Sarcocystis species are intracellular protozoan parasites with an intermediate
      definitive host life cycle based on a prey-predator relationship. Asexual stages
      develop in intermediate hosts after they ingest the oocyst stage from definitive
      host feces and terminate with the formation of intramuscular cysts (sarcocysts).
      Sarcocysts in meat eaten by a definitive host initiate sexual stages in the
      intestine that terminate in oocysts excreted in the feces. Most Sarcocystis
      species infect specific hosts or closely related host species. For example,
      humans and some primates are definitive hosts for Sarcocystis hominis and S.
      suihominis after eating raw meat from cattle and pigs, respectively. The
      prevalence of intestinal sarcocystosis in humans is low and is only rarely
      associated with illness, except in volunteers who ingest large numbers of
      sarcocysts. Cases of infection of humans as intermediate hosts, with
      intramuscular cysts, number less than 100 and are of unknown origin. The asexual
      stages, including sarcocysts, can stimulate a strong inflammatory response.
      Livestock have suffered acute debilitating infections, resulting in abortion and
      death or chronic infections with failure to grow or thrive. This review provides
      a summary of Sarcocystis biology, including its morphology, life cycle, host
      specificity, prevalence, diagnosis, treatment, and prevention strategies, for
      human and food animal infections.

PMID- 15489354
TI  - Molecular methods for diagnosis of viral encephalitis.
AB  - Hundreds of viruses cause central nervous system (CNS) disease, including
      meningoencephalitis and postinfectious encephalomyelitis, in humans. The
      cerebrospinal fluid (CSF) is abnormal in >90% of cases; however, routine CSF
      studies only rarely lead to identification of a specific etiologic agent.
      Diagnosis of viral infections of the CNS has been revolutionized by the advent of
      new molecular diagnostic technologies to amplify viral nucleic acid from CSF,
      including PCR, nucleic acid sequence-based amplification, and branched-DNA assay.
      PCR is ideally suited for identifying fastidious organisms that may be difficult
      or impossible to culture and has been widely applied for detection of both DNA
      and RNA viruses in CSF. The technique can be performed rapidly and inexpensively
      and has become an integral component of diagnostic medical practice in the United
      States and other developed countries. In addition to its use for identification
      of etiologic agents of CNS disease in the clinical setting, PCR has also been
      used to quantitate viral load and monitor duration and adequacy of antiviral drug
      therapy. PCR has also been applied in the research setting to help discriminate
      active versus postinfectious immune-mediate disease, identify determinants of
      drug resistance, and investigate the etiology of neurologic disease of uncertain
      cause. This review discusses general principles of PCR and reverse transcription
      PCR, including qualitative, quantitative, and multiplex techniques, with comment
      on issues of sensitivity, specificity, and positive and negative predictive
      values. The application of molecular diagnostic methods for diagnosis of specific
      infectious entities is reviewed in detail, including viruses for which PCR is of
      proven efficacy and is widely available, viruses for which PCR is less widely
      available or for which PCR has unproven sensitivity and specificity, and nonviral
      entities which can mimic viral CNS disease.

PMID- 15489355
TI  - Antibody therapy in the management of shiga toxin-induced hemolytic uremic
      syndrome.
AB  - Hemolytic uremic syndrome (HUS) is a disease that can lead to acute renal failure
      and often to other serious sequelae, including death. The majority of cases are
      attributed to infections with Escherichia coli, serotype O157:H7 strains in
      particular, which cause bloody diarrhea and liberate one or two toxins known as
      Shiga toxins 1 and 2. These toxins are thought to directly be responsible for the
      manifestations of HUS. Currently, supportive nonspecific treatment is the only
      available option for the management of individuals presenting with HUS. The
      benefit of antimicrobial therapy remains uncertain because of several reports
      which claim that such intervention can in fact exacerbate the syndrome. There
      have been only a few specific therapies directed against neutralizing the
      activities of these toxins, but none so far has been shown to be effective. This
      article reviews the literature on the mechanism of action of these toxins and the
      clinical manifestations and current management and treatment of HUS. The major
      focus of the article, however, is the development and rationale for using
      neutralizing human antibodies to combat this toxin-induced disease. Several
      groups are currently pursuing this approach with either humanized, chimeric, or
      human antitoxin antibodies produced in transgenic mice. They are at different
      phases of development, ranging from preclinical evaluation to human clinical
      trials. The information available from preclinical studies indicates that
      neutralizing specific antibodies directed against the A subunit of the toxin can
      be highly protective. Such antibodies, even when administered well after exposure
      to bacterial infection and onset of diarrhea, can prevent the occurrence of
      systemic complications.

PMID- 15489352
TI  - Epidemiologic background of hand hygiene and evaluation of the most important
      agents for scrubs and rubs.
AB  - The etiology of nosocomial infections, the frequency of contaminated hands with
      the different nosocomial pathogens, and the role of health care workers' hands
      during outbreaks suggest that a hand hygiene preparation should at least have
      activity against bacteria, yeasts, and coated viruses. The importance of efficacy
      in choosing the right hand hygiene product is reflected in the new Centers for
      Disease Control and Prevention guideline on hand hygiene (J. M. Boyce and D.
      Pittet, Morb. Mortal. Wkly. Rep. 51:1-45, 2002). The best antimicrobial efficacy
      can be achieved with ethanol (60 to 85%), isopropanol (60 to 80%), and n-propanol
      (60 to 80%). The activity is broad and immediate. Ethanol at high concentrations
      (e.g., 95%) is the most effective treatment against naked viruses, whereas n
      propanol seems to be more effective against the resident bacterial flora. The
      combination of alcohols may have a synergistic effect. The antimicrobial efficacy
      of chlorhexidine (2 to 4%) and triclosan (1 to 2%) is both lower and slower.
      Additionally, both agents have a risk of bacterial resistance, which is higher
      for chlorhexidine than triclosan. Their activity is often supported by the
      mechanical removal of pathogens during hand washing. Taking the antimicrobial
      efficacy and the mechanical removal together, they are still less effective than
      the alcohols. Plain soap and water has the lowest efficacy of all. In the new
      Centers for Disease Control and Prevention guideline, promotion of alcohol-based
      hand rubs containing various emollients instead of irritating soaps and
      detergents is one strategy to reduce skin damage, dryness, and irritation.
      Irritant contact dermatitis is highest with preparations containing 4%
      chlorhexidine gluconate, less frequent with nonantimicrobial soaps and
      preparations containing lower concentrations of chlorhexidine gluconate, and
      lowest with well-formulated alcohol-based hand rubs containing emollients and
      other skin conditioners. Too few published data from comparative trials are
      available to reliably rank triclosan. Personnel should be reminded that it is
      neither necessary nor recommended to routinely wash hands after each application
      of an alcohol-based hand rub. Long-lasting improvement of compliance with hand
      hygiene protocols can be successful if an effective and accessible alcohol-based
      hand rub with a proven dermal tolerance and an excellent user acceptability is
      supplied, accompanied by education of health care workers and promotion of the
      use of the product.

PMID- 15489357
TI  - The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection
      differ between men and women.
AB  - The molecular mechanisms used by the gonococcus to initiate infection exhibit
      gender specificity. The clinical presentations of disease are also strikingly
      different upon comparison of gonococcal urethritis to gonococcal cervicitis. An
      intimate association occurs between the gonococcus and the urethral epithelium
      and is mediated by the asialoglycoprotein receptor. Gonococcal interaction with
      the urethral epithelia cell triggers cytokine release, which promotes neutrophil
      influx and an inflammatory response. Similarly, gonococcal infection of the upper
      female genital tract also results in inflammation. Gonococci invade the
      nonciliated epithelia, and the ciliated cells are subjected to the cytotoxic
      effects of tumor necrosis factor alpha induced by gonococcal peptidoglycan and
      lipooligosaccharide. In contrast, gonococcal infection of the lower female
      genital tract is typically asymptomatic. This is in part the result of the
      ability of the gonococcus to subvert the alternative pathway of complement
      present in the lower female genital tract. Gonococcal engagement of complement
      receptor 3 on the cervical epithelia results in membrane ruffling and does not
      promote inflammation. A model of gonococcal pathogenesis is presented in the
      context of the male and female human urogenital tracts.

PMID- 15489360
TI  - Evolution and survival of the fittest.

PMID- 15489356
TI  - Role of microglia in central nervous system infections.
AB  - The nature of microglia fascinated many prominent researchers in the 19th and
      early 20th centuries, and in a classic treatise in 1932, Pio del Rio-Hortega
      formulated a number of concepts regarding the function of these resident
      macrophages of the brain parenchyma that remain relevant to this day. However, a
      renaissance of interest in microglia occurred toward the end of the 20th century,
      fueled by the recognition of their role in neuropathogenesis of infectious
      agents, such as human immunodeficiency virus type 1, and by what appears to be
      their participation in other neurodegenerative and neuroinflammatory disorders.
      During the same period, insights into the physiological and pathological
      properties of microglia were gained from in vivo and in vitro studies of
      neurotropic viruses, bacteria, fungi, parasites, and prions, which are reviewed
      in this article. New concepts that have emerged from these studies include the
      importance of cytokines and chemokines produced by activated microglia in
      neurodegenerative and neuroprotective processes and the elegant but astonishingly
      complex interactions between microglia, astrocytes, lymphocytes, and neurons that
      underlie these processes. It is proposed that an enhanced understanding of
      microglia will yield improved therapies of central nervous system infections,
      since such therapies are, by and large, sorely needed.

PMID- 15489361
TI  - The William Houston Medal of the MOrth of the Royal College of Surgeons of
      Edinburgh 2003 and the BOS MOrth Cases Prize 2003.
AB  - This paper describes the orthodontic treatment of 2 cases that were presented by
      the winner of the William Houston Medal of the MOrth of the Royal College of
      Surgeons of Edinburgh at the June 2003 diet of the examination. The cases were
      also successful presented for the British Orthodontic Society MOrth Cases Prize
      2003.

PMID- 15489358
TI  - Diagnosis and assessment of trachoma.
AB  - Trachoma is caused by Chlamydia trachomatis. Clinical grading with the WHO
      simplified system can be highly repeatable provided graders are adequately
      trained and standardized. At the community level, rapid assessments are useful
      for confirming the absence of trachoma but do not determine the magnitude of the
      problem in communities where trachoma is present. New rapid assessment protocols
      incorporating techniques for obtaining representative population samples (without
      census preparation) may give better estimates of the prevalence of clinical
      trachoma. Clinical findings do not necessarily indicate the presence or absence
      of C. trachomatis infection, particularly as disease prevalence falls. The
      prevalence of ocular C. trachomatis infection (at the community level) is
      important because it is infection that is targeted when antibiotics are
      distributed in trachoma control campaigns. Methods to estimate infection
      prevalence are required. While culture is a sensitive test for the presence of
      viable organisms and nucleic acid amplification tests are sensitive and specific
      tools for the presence of chlamydial nucleic acids, the commercial assays
      presently available are all too expensive, too complex, or too unreliable for use
      in national programs. There is an urgent need for a rapid, reliable test for C.
      trachomatis to assist in measuring progress towards the elimination of trachoma.

PMID- 15489362
TI  - A paralleling device and ethylene vinyl acetate baffles for use with mandibular
      distraction osteogenesis: technical note.
AB  - A novel method for planning the placement of intra-oral lengthening devices using
      a paralleling device is described and illustrated with a case report. Simple
      radiographic measurements and study models are all that is required to construct
      a simple acrylic splint with guides, which allows accurate positioning of the
      distractors at surgery. The construction of ethylene vinyl acetate (EVA) baffles
      to prevent trauma to the labial mucosa from the intra-oral link arms is a
      technique that enhances patient comfort during distraction of the mandible. The
      case report demonstrates the application of the surgical planning technique and
      the use of EVA baffles for a patient with an overjet of 21.5 mm.

PMID- 15489364
TI  - Lay person's perception of smile aesthetics in dental and facial views.
AB  - OBJECTIVE: To compare the aesthetic perception of different anterior visible
      occlusions in different facial and dental views (frontal view, lower facial third
      view and dental view) by lay persons. DESIGN: Cross-sectional survey, Lima, Peru,
      2002. SUBJECTS: The different views were rated by 91 randomly selected adult lay
      persons. MAIN OUTCOME MEASUREMENT: Visual Analogue Scale (VAS) ratings of
      aesthetic perception of the views. RESULTS: Anterior visible occlusion,
      photographed subject and view (p<0.001) had a significant effect on the aesthetic
      ratings. Also gender (p=0.001) and the interaction between gender and level of
      education (p=0.046) had a significant effect over the aesthetic rating.
      CONCLUSIONS: A lay panel perceived that the aesthetic impact of the visible
      anterior occlusion was greater in a dental view compared with a full facial view.
      The anterior visible occlusion, photographed subject, view type are factors,
      which influence the aesthetic perception of smiles. In addition, gender and level
      of education had an influence.

PMID- 15489363
TI  - Treatment of hemifacial microsomia in a growing child: the importance of co
      operation between the orthodontist and the maxillofacial surgeon.
AB  - The treatment of patients with hemifacial microsomia (HM) always requires an
      interdisciplinary approach including at least maxillofacial surgery and
      orthodontics. Co-operation not only within the team, but also with the patients
      and their family is essential in order to achieve the best results. In the case
      history of the 10-(1/2) year old female patient reported here, three surgical
      interventions (two with costo-chondral bone grafts) and a 3-year orthodontic
      treatment have taken place. A harmonious facial and occlusal result was finally
      reached.

PMID- 15489365
TI  - How readable are orthodontic patient information leaflets?
AB  - OBJECTIVE: To assess the readability of published orthodontic patient information
      leaflets (PILs) and their eligibility for the Plain English Campaign's Crystal
      Mark. DESIGN: A retrospective, observational study. SETTING: PILs available from
      professional organizations and commercial companies. MATERIALS AND METHODS:
      Twenty-six orthodontic PILs were assessed. The entire text of each leaflet was
      reproduced in Microsoft Word, 2000. Readability statistics were obtained via the
      'Tools' menu. The design elements of each leaflet were assessed. The leaflets
      were sent to the Plain English Campaign for assessment of their eligibility for
      the Crystal Mark. OUTCOME MEASURES: Leaflet and sentence length, passive
      percentage, Flesch Reading Ease score, Flesch Kincaid Grade Level, design
      percentage and eligibility for the Plain English Campaign's Crystal Mark.
      RESULTS: Overall, nearly half of the leaflets (42.3%) were rated as 'fairly
      difficult' or 'difficult' to read. However, the BOS PILs were significantly
      better than the AAO leaflets in all but one outcome with the BOS leaflets being
      rated as 'standard' or 'fairly easy' to read, meaning that 70-80% of the UK
      population would be able to understand them. None of the PILs were eligible for
      the Plain English Campaign's Crystal Mark. CONCLUSIONS: The orthodontic PILs
      assessed were difficult to read and none were eligible for the Plain English
      Campaign's Crystal Mark. However, the BOS leaflets were much easier to read and
      better designed than those produced by the AAO making them a useful tool to
      improve patients' understanding of different treatment options and allowing them
      to be used in the informed consent process.

PMID- 15489366
TI  - The development of a patient-centered measure of the process and outcome of
      combined orthodontic and orthognathic treatment.
AB  - OBJECTIVE: The aim of this study was to develop a patient-based measure of the
      process and outcome of combined orthodontic and orthognathic care in the National
      Health Service in the UK. DESIGN: Identification of relevant dimensions through
      qualitative methods, design of form, determination of psychometric properties of
      the scale, specific readability, reliability and validity. SETTING: NHS hospitals
      in the South West Region. SUBJECTS: The sample comprised patients who had
      received combined orthodontic and orthognathic treatment between 01 January 1998
      and 31 December 2000. Twenty-six participants (a 25% response rate) took part in
      four focus group meetings. Thirty subjects (65% response rate) took part in a
      pilot study to test the properties of the questionnaire. MAIN OUTCOME MEASURES:
      Six broad themes emerged from the focus groups. These formed the basis of the
      sections in the questionnaire. RESULTS: The questionnaire developed had a Flesch
      reading ease score of 72.9 or US grade level 4 equivalent to aged 9-10 years.
      Test-retest reliability gave kappa values for most questions that exceeded 0.4.
      Criterion validity of the measure was established by comparing responses to the
      questionnaire over two periods with a telephone interview on a sample of 30
      patients. Criterion related validity was poor for nine of the 16 items. By
      contrast the construct validity of the questionnaire was satisfactory.
      CONCLUSION: A patient-based measure of the process and outcome of combined
      orthodontic and orthognathic treatment has been developed. This has sufficient
      validity and reliability for use in inter-center audit projects.

PMID- 15489359
TI  - Chronic immune activation associated with chronic helminthic and human
      immunodeficiency virus infections: role of hyporesponsiveness and anergy.
AB  - Chronic immune activation is one of the hallmarks of human immunodeficiency virus
      (HIV) infection. It is present also, with very similar characteristics, in very
      large human populations infested with helminthic infections. We have tried to
      review the studies addressing the changes in the immune profiles and responses of
      hosts infected with either one of these two chronic infections. Not surprisingly,
      several of the immune derangements and impairments seen in HIV infection, and
      considered by many to be the "specific" effects of HIV, can be found in helminth
      infected but HIV-noninfected individuals and can thus be accounted for by the
      chronic immune activation itself. A less appreciated element in chronic immune
      activation is the immune suppression and anergy which it may generate. Both HIV
      and helminth infections represent this aspect in a very wide and illustrative
      way. Different degrees of anergy and immune hyporesponsiveness are present in
      these infections and probably have far-reaching effects on the ability of the
      host to cope with these and other infections. Furthermore, they may have
      important practical implications, especially with regard to protective
      vaccinations against AIDS, for populations chronically infected with helminths
      and therefore widely anergic. The current knowledge of the mechanisms responsible
      for the generation of anergy by chronic immune activation is thoroughly reviewed.

PMID- 15489367
TI  - White lesions after orthodontic treatment: does low fluoride make a difference?
AB  - OBJECTIVE: To compare and measure the changes in size of post-orthodontic
      demineralized white lesion enamel lesions treated with a low fluoride (50 ppm)
      versus a non-fluoride mouthrinse/toothpaste regime. STUDY DESIGN: An experimental
      double-blind prospective randomized clinical controlled trial. SETTING: A
      university dental school orthodontic clinic (Sheffield, UK). PARTICIPANTS: Twenty
      six patients identified as having post-orthodontic demineralized white lesions on
      removal of their fixed appliance. METHOD AND INTERVENTIONS: The participants were
      randomly and blindly assigned to either a low fluoride mouthrinse/toothpaste
      treatment regime or an inactive control. Computerized image analysis of
      calibrated photographic images taken under polarized light were used to measure
      the lesions. OUTCOME MEASURES: Lesion size and proportion (DWL%t) and percentage
      reduction (ADPR) at debond, and at 12 and 26 weeks later. RESULTS: Five
      participants dropped out of the study, 12 had the low fluoride regime and 9 did
      not. As a percentage of the total labial tooth area (DWL%t) the mean size of the
      lesions at debond was 8.1% (SD 3.7). After 12 weeks the mean size of lesion had
      reduced to 4.6% (SD 2.6), which was a significant reduction (p=0.03). After 26
      weeks the mean size was 3.5% (SD 2.1), which was a very significant reduction
      (p<0.003). This confirmed statistically that post-orthodontic demineralized white
      lesions do reduce in size with time reflecting remineralization or other enamel
      surface changes. Intervention using a test low fluoride mouthrinse/toothpaste
      combination at 26 weeks showed an average difference percentage reduction (ADPR)
      of 54.3% (Upper 95% CI=62.08, Lower 95% CI=46.44%) compared with a non-active
      control combination, which showed an ADPR of 66.1% (Upper 95% CI=77.74, Lower 95%
      CI=54.51%). This failed to show any differences or therapeutic affect.
      CONCLUSIONS: Post-orthodontic demineralized white lesions reduced in size during
      the 6 months following treatment by approximately half the original size. There
      was no clinical advantage in using the low fluoride formulation of
      mouthrinse/toothpaste in this study.

PMID- 15489368
TI  - A comparison of three light curing units for bonding adhesive pre-coated
      brackets.
AB  - OBJECTIVE: To compare the effectiveness of three curing lights of different
      types. DESIGN: Prospective randomized laboratory investigations. MATERIALS AND
      METHOD: Adhesive pre-coated orthodontic brackets were bonded to 9 groups of
      extracted premolars and the adhesive was cured using three different curing
      lights, each at three different times. Bond strength was tested using a
      shear/peel method. RESULTS: The plasma light had 3 times the light intensity of
      the standard quartz halogen light. The curing times recommended by the
      manufacturers were 2 seconds for the plasma light, 10 seconds for the high
      intensity quartz halogen light and 20 seconds for the standard one. Mean debond
      stresses with these cure times were 9.36, 11.77 and 12.00 MPa, respectively,
      p<0.04. Increasing the plasma light cure to 4 seconds increased the mean debond
      stress to 11.19 MPa, similar to that for the other lights, p=0.62. CONCLUSIONS:
      Use of a plasma light confers worthwhile time savings when bonding orthodontic
      brackets, whilst producing bonds of equivalent strength to those found with
      quartz halogen lights.

PMID- 15489369
TI  - How to effectively use a 2 x 4 appliance.
AB  - A mixed dentition treatment can efficiently and effectively be provided using a 2
      x 4 appliance. The indications for early treatment are discussed and advantages
      of fixed appliances over traditionally used removable appliances illustrated
      using four case reports.

PMID- 15489371
TI  - Current products and practices: curriculum development in orthodontic specialist
      registrar training: can orthodontics achieve constructive alignment?
AB  - This paper aims to encourage a debate on the learning outcomes that have been
      developed for orthodontic specialist education. In outcome-based education the
      learning outcomes are clearly defined. They determine curriculum content and its
      organization, the teaching and learning approaches, the assessment techniques and
      hope to focus the minds of the students on ensuring all the learning outcomes are
      met. In Orthodontic Specialist Registrar training, whether constructive alignment
      can be achieved depends on the relationship between these aspects of the
      education process and the various bodies responsible for their delivery in the
      UK.

PMID- 15489373
TI  - Pulmonary inflammation induced by high-stretch ventilation is mediated by tumor
      necrosis factor signaling in mice.
AB  - Although high-stretch mechanical ventilation has been demonstrated to induce lung
      inflammation, the roles of soluble mediators, in particular TNF, remain
      controversial. We have previously shown in mice that high-stretch ventilation, in
      the absence of preceding lung injury, induces expression of bioactive TNF in lung
      lavage fluid early in the course of injury, but the biological significance of
      this, if any, has yet to be determined. We therefore investigated the pulmonary
      inflammatory response to a transient period of high-stretch ventilation in
      anesthetized mice lacking TNF receptors and mice treated with anti-TNF
      antibodies. A standardized stretch-induced lung injury (assessed by lung
      mechanics, blood gases, and lavage protein content), followed by noninjurious low
      stretch ventilation for 3 h, produced significant alveolar neutrophil
      infiltration in wild-type mice. However, neutrophil recruitment was substantially
      attenuated in TNF receptor double knockout mice and in wild-type mice treated
      with intratracheal anti-TNF antibody. This attenuation was not associated with
      decreased concentrations of neutrophil attractant CXC chemokines (macrophage
      inflammatory protein-2 and keratinocyte-derived chemokine) in lavage fluid. In
      contrast to intratracheal antibody, intravenous anti-TNF antibody did not reduce
      neutrophil infiltration, suggesting that the role of TNF signaling is localized
      within the alveolar space and does not require decompartmentalization of TNF into
      the circulation. These findings provide the first direct evidence that pulmonary
      inflammation induced by high-stretch ventilation without underlying lung injury
      possesses a significant TNF-dependent component. The results suggest a potential
      for regional anti-TNF treatment in attenuating stretch-induced pulmonary
      inflammation.

PMID- 15489374
TI  - Involvement of p42/p44 MAPK, p38 MAPK, JNK, and NF-kappaB in IL-1beta-induced
      VCAM-1 expression in human tracheal smooth muscle cells.
AB  - Interleukin-1beta (IL-1beta) has been shown to induce the expression of adhesion
      molecules on airway epithelial and smooth cells and contributes to inflammatory
      responses. Here, the roles of mitogen-activated protein kinases (MAPKs) and
      nuclear factor-kappaB (NF-kappaB) pathways for IL-1beta-induced vascular cell
      adhesion molecule (VCAM)-1 expression were investigated in human tracheal smooth
      muscle cells (HTSMC). IL-1beta induced expression of VCAM-1 protein and mRNA in a
      time-dependent manner, which was significantly inhibited by inhibitors of MEK1/2
      (U0126 and PD-98059), p38 (SB-202190), and c-Jun NH(2)-terminal kinase (JNK; SP
      600125). Consistently, IL-1beta-stimulated phosphorylation of p42/p44 MAPK, p38,
      and JNK was attenuated by pretreatment with U0126, SB-202190, or SP-600125,
      respectively. IL-1beta-induced VCAM-1 expression was significantly blocked by the
      specific NF-kappaB inhibitors helenalin and pyrrolidine dithiocarbamate. As
      expected, IL-1beta-stimulated translocation of NF-kappaB into the nucleus and
      degradation of IkappaB-alpha were blocked by helenalin but not by U0126, SB
      202190, or SP-600125. Moreover, the resultant enhancement of VCAM-1 expression
      increased the adhesion of polymorphonuclear cells to a monolayer of HTSMC, which
      was blocked by pretreatment with helenalin, U0126, SB-202190, or SP-600125 before
      IL-1beta exposure or by anti-VCAM-1 antibody. Together, these results suggest
      that in HTSMC, activation of p42/p44 MAPK, p38, JNK, and NF-kappaB pathways is
      essential for IL-1beta-induced VCAM-1 gene expression. These results provide new
      insight into the mechanisms of IL-1beta action that cytokines may promote
      inflammatory responses in airway disease.

PMID- 15489375
TI  - VCAM-1 upregulation via PKCdelta-p38 kinase-linked cascade mediates the TNF-alpha
      induced leukocyte adhesion and emigration in the lung airway epithelium.
AB  - Vascular cell adhesion molecule (VCAM)-1 plays a central role in the recruitment
      of inflammatory cells, and its expression is rapidly induced by proinflammatory
      cytokines such as TNF-alpha. In the present study, we show that pretreatment with
      rottlerin, a specific inhibitor of protein kinase C (PKC)-delta, or transient
      transfection with antisense PKCdelta oligonucleotides significantly inhibits TNF
      alpha-induced expression of VCAM-1, but not of intercellular adhesion molecule
      (ICAM)-1 in human lung epithelium A549 cells. In addition, TNF-alpha was shown to
      induce the expression of VCAM-1 in a p38 kinase-dependent manner; also, TNF-alpha
      induced p38 kinase activation was blocked by inhibition of PKCdelta, suggesting
      that p38 kinase is apparently situated downstream of PKCdelta in the TNF-alpha
      signaling pathway to VCAM-1 expression. Notably, inhibition of the PKCdelta-p38
      kinase cascade also attenuated the TNF-alpha-induced adhesion of neutrophils to
      lung epithelium and the trafficking of leukocytes across the epithelium into the
      airway lumen in vivo. Together, these findings indicate that signaling via
      PKCdelta-p38 kinase-linked cascade specifically induces expression of VCAM-1 in
      lung epithelium in response to TNF-alpha and that this effect is both
      functionally and clinically significant.

PMID- 15489376
TI  - Neurology postgraduate training: what is to be done?

PMID- 15489377
TI  - Enlarged Virchow-Robin spaces: do they matter?

PMID- 15489378
TI  - Neurology postgraduate training: what is to be done?

PMID- 15489379
TI  - Longer term outcome of children born to mothers with epilepsy.

PMID- 15489380
TI  - Enlarged perivascular spaces are associated with cognitive function in healthy
      elderly men.
AB  - OBJECTIVES: Increased white matter (WM) lesions on magnetic resonance imaging
      (MRI) are associated with worse cognitive function in older people. Enlarged
      perivascular spaces (EPVS) commonly coexist with and share some risk factors for
      WM lesions but are not quantified in published scales. It is not known whether
      the extent of EPVS is also associated with cognitive function. We tested the
      hypothesis that more EPVS would be associated with worse cognitive function.
      METHODS: Ninety seven healthy men (65-70 years), not on medications, underwent
      MRI scanning and comprehensive cognitive testing. EPVS were quantified in both
      the basal ganglia/centrum semiovale and the hippocampus, and WM lesions were
      measured. RESULTS: Scores on published WM lesion rating scales intercorrelated
      highly significantly and positively (rho = 0.61 to 0.91, p<0.0001). A summary
      (WML) factor derived from principal components analysis of the WM scales
      correlated with EPVS in the basal ganglia/centrum semiovale (rho = 0.48,
      p<0.0001) but not in the hippocampus. EPVS scores in the basal ganglia/centrum
      semiovale correlated significantly and negatively with non-verbal reasoning (rho
      = -0.21, p = 0.038) and general visuospatial ability (rho = -0.22, p = 0.032),
      adjusted for prior intelligence. The WML factor correlated significantly and
      negatively with visuospatial ability, as previously reported, and showed an
      unexpected positive correlation with one test of verbal memory (list-learning).
      CONCLUSIONS: These findings suggest that increased EPVS are correlated with worse
      cognitive function. Future studies examining changes in WM with ageing should
      consider incorporating measures of EPVS and examine the sequence of EPVS and WM
      lesion development over time. More work is needed to develop valid and reliable
      measures of EPVS.

PMID- 15489381
TI  - Evidence for distinct cognitive deficits after focal cerebellar lesions.
AB  - OBJECTIVES: Anatomical evidence and lesion studies, as well as functional
      magnetic resonance imaging (fMRI) studies, indicate that the cerebellum
      contributes to higher cognitive functions. Cerebellar posterior lateral regions
      seem to be relevant for cognition, while vermal lesions seem to be associated
      with changes in affect. However, the results remain controversial. Deficits of
      patients are sometimes still attributed to motor impairment. METHODS: We present
      data from a detailed neuropsychological examination of 21 patients with
      cerebellar lesions due to tumour or haematoma, and 21 controls matched for age,
      sex, and years of education. RESULTS: Patients showed deficits in executive
      function, and in attentional processes such as working memory and divided
      attention. Further analysis revealed that patients with right-sided lesions were
      in general more impaired than those with left-sided lesions. CONCLUSIONS: Those
      hypotheses that suggest that lesions of the right cerebellar hemisphere lead to
      verbal deficits, while those of the left lead to non-verbal deficits, have in
      part been confirmed. The generally greater impairment of those patients with a
      right-sided lesion has been interpreted as resulting from the connection of the
      right cerebellum to the left cerebral hemisphere, which is dominant for language
      functions and crucial for right hand movements. Motor impairment was correlated
      with less than half of the cognitive measures, with no stronger tendency for
      correlation with cognitive tests that require motor responses discernible. The
      results are discussed on the basis of an assumption that the cerebellum has a
      predicting and preparing function, indicating that cerebellar lesions lead to a
      "dysmetria of thought."

PMID- 15489382
TI  - The dynamic time course of memory recovery in transient global amnesia.
AB  - AIMS: To investigate the dynamic time course of transient global amnesia (TGA)-
      that is, the process of recovery and the interindividual variability--by testing
      four patients during the day of TGA itself (on three occasions) and at follow up
      (on two occasions). METHODS: A specially designed protocol focusing on semantic
      (both conceptual and autobiographical knowledge) and episodic (both anterograde
      and retrograde components) memory. RESULTS: Every patient showed marked
      impairment of both anterograde and retrograde episodic memory during the acute
      phase, with a relative preservation of personal and conceptual semantic
      knowledge. During the following phase, the authors observed similarities and
      differences among the patients' patterns of recovery. In general, retrograde
      amnesia recovered before the anterograde amnesia and anterograde episodic memory
      was recovered gradually in every case. In contrast, shrinkage of retrograde
      amnesia was more heterogeneous. In two of the patients, this shrinkage followed a
      chronological gradient and the most remote events were recovered first. In the
      two other patients, it depended more on the strength of the trace, and there was
      no temporal gradient. For the latter, an executive deficit could account for
      difficulties in accessing both conceptual knowledge and autobiographical
      memories. CONCLUSIONS: This profile of recovery suggests a "neocortical to medial
      temporal" process in every case, and the possibility of an additional frontal
      dysfunction in some cases. Hence, the acute phase seems to be characterised by a
      common episodic impairment. This variability between subjects appears in the
      recovery phase with two different patterns of impairment.

PMID- 15489383
TI  - Effects of botulinum toxin type A on vibration induced facilitation of motor
      evoked potentials in spasmodic torticollis.
AB  - BACKGROUND AND AIMS: It has not been clarified if botulinum toxin (BTX) injection
      leads to muscle spindle dysfunction in man. This study aimed to test the
      hypothesis that BTX application reduces the facilitation of a magnetic evoked
      response (MEP). METHODS: We used the vibration induced facilitation of an MEP of
      the sternocleidomastoid muscle (SCM) as a surrogate marker for muscle spindle
      function in 20 healthy subjects and 10 patients with idiopathic rotational
      torticollis in whom BTX was injected unilaterally. RESULTS: The increase in the
      amplitude and area of the MEPs in the clinically not affected and untreated SCM
      of the patients did not differ significantly from the controls. At baseline, the
      vibration induced increase in the affected SCM of the patients was significantly
      lower than in the control group. Six weeks after BTX application, the observed
      facilitation decreased significantly (amplitude and area: p<0.001) when compared
      with baseline values. Twelve weeks after BTX application, facilitation showed an
      increase in the values of the amplitude (p<0.001), but not of the area when
      compared with the six week examination. CONCLUSIONS: We demonstrated that the
      vibration induced MEP facilitation in the SCM of patients with torticollis
      significantly decreased six weeks after BTX application and again increased after
      12 weeks in part when looking at MEP amplitude. This observation is suggestive of
      denervation and reinnervation of the muscle spindles after BTX injection.

PMID- 15489384
TI  - Does reducing spasticity translate into functional benefit? An exploratory meta
      analysis.
AB  - BACKGROUND: Spasticity and loss of function in an affected arm are common after
      stroke. Although botulinum toxin is used to reduce spasticity, its functional
      benefits are less easily demonstrated. This paper reports an exploratory meta
      analysis to investigate the relationship between reduced arm spasticity and
      improved arm function. METHOD: Individual data from stroke patients in two
      randomised controlled trials of intra-muscular botulinum toxin were pooled. The
      Modified Ashworth Scale (elbow, wrist, fingers) was used to calculate a
      "Composite Spasticity Index". Data from the arm section of the Barthel Activities
      of Daily Living Index (dressing, grooming, and feeding) and three subjective
      measures (putting arm through sleeve, cleaning palm, cutting fingernails) were
      summed to give a "Composite Functional Index". Change scores and the time of
      maximum change were also calculated. RESULTS: Maximum changes in both composite
      measures occurred concurrently in 47 patients. In 26 patients the improvement in
      spasticity preceded the improvement in function with 18 showing the reverse.
      There was a definite relationship between the maximum change in spasticity and
      the maximum change in arm function, independent of treatment (rho = -0.2822, p =
      0.0008, n = 137). There was a clear relationship between the changes in
      spasticity and in arm function in patients treated with botulinum toxin (Dysport)
      at 500 or 1000 units (rho = -0.5679, p = 0.0090, n = 22; rho = -0.4430, p =
      0.0018, n = 47), but not in those treated with placebo or 1500 units.
      CONCLUSIONS: Using a targeted meta-analytic approach, it is possible to
      demonstrate that reducing spasticity in the arm is associated with a significant
      improvement in arm function.

PMID- 15489385
TI  - Salk and Sabin: poliomyelitis immunisation.

PMID- 15489386
TI  - Long term effect (more than five years) of intrathecal baclofen on impairment,
      disability, and quality of life in patients with severe spasticity of spinal
      origin.
AB  - OBJECTIVES: To evaluate long term change in impairment, disability, and health
      related functional status in patients with severe spasticity who received
      intrathecal baclofen. METHODS: A long term (more than five years) observational
      longitudinal follow up study assessing 21 patients who received intrathecal
      baclofen given by programmable pump. Patients had chronic disabling spasticity
      which did not respond to oral antispasmolytic agents. Clinical efficacy was
      assessed by the Ashworth scale and spasm score; disability by the expanded
      disability status scale (EDSS), ambulation index (AI), and incapacity status
      scale (ISS); and health related quality of life by the sickness impact profile
      (SIP) and the Hopkins symptom checklist (HSCL). RESULTS: Compared with
      pretreatment values, there was a significant improvement in clinical efficacy
      (Ashworth scale and spasm score, p<0.05) but a small but significant worsening of
      disability (EDSS, AI, and ISS, p<0.05). Comparing pretreatment with 26 weeks
      after pump implantation, a worsening was observed in disability (EDSS and ISS,
      p<0.05) and perceived health status (SIP, psychosocial dimension, p<0.05).
      CONCLUSIONS: Long term administration of intrathecal baclofen delivered by an
      implanted programmable pump resulted in improved clinical efficacy but not in
      improvement in disability or perceived health status.

PMID- 15489387
TI  - The beneficial antispasticity effect of botulinum toxin type A is maintained
      after repeated treatment cycles.
AB  - OBJECTIVE: To study the efficacy, safety, and incidence of BtxA antibody
      formation with repeated treatments with BtxA in post-stroke upper limb muscle
      spasticity. METHODS: The study was a prospective open label trial. Patients with
      established post-stroke upper limb spasticity received 1000 units of BtxA
      (Dysport) into five muscles of the affected arm on study entry. Treatment was
      repeated every 12, 16, or 20 weeks as clinically indicated. Each patient received
      a total of three treatment cycles. Efficacy of treatment was assessed using the
      Modified Ashworth Scale. Patients were assessed on study entry and on week 4 and
      12 of each treatment cycle for all safety and efficacy parameters. Blood samples
      for BtxA antibody assay were taken at baseline and on completion of the trial.
      RESULTS: Fifty one patients were recruited and 41 of them completed the study.
      Improvement from the cycle one baseline was observed in all the outcome measures.
      Mild to moderately severe treatment related adverse events were reported in 24%
      of cases. There were no serious adverse events. No BtxA antibodies were detected.
      CONCLUSION: BtxA at a dose of 1000 units Dysport was efficacious in the
      symptomatic treatment of post-stroke upper limb spasticity. The study suggests
      that this effect can be maintained with repeated injections for up to at least
      three treatment cycles, with duration of effect per cycle of between 12 and 20
      weeks. BtxA was safe in the dose used in this study and did not induce the
      formation of detectable levels of neutralising BtxA antibodies.

PMID- 15489388
TI  - Demographic and CT scan features related to cognitive impairment in the first
      year after stroke.
AB  - OBJECTIVE: Little is known about the relation between stroke related features and
      cognitive performance over time when stroke patients with dementia or less severe
      cognitive disorders are considered separately. We aimed to study the features
      (computed tomography (CT) scan and demographic) that could be related to vascular
      cognitive impairment one, six, and 12 months after stroke. METHODS: A total of
      176 patients with a first-ever brain infarct, a Mini Mental State Examination
      score > or = 15, age older than 40 years, and without pre-stroke dementia and
      other neurological or psychiatric disorders participated in this study. The
      following CT scan features were recorded: side of infarct, lacunar or territorial
      infarct, white matter lesions, silent infarcts, and brain atrophy. The
      demographic features studied were: age, level of education, and sex. Univariate
      and multivariate logistic regression analyses were performed to compare the three
      groups of patients (patients with dementia, patients with vascular cognitive
      impairment (VCI), and patients with vascular mild cognitive impairment (MCI))
      with patients without cognitive disorders. RESULTS: At one month none of the
      variables were predictors of dementia; at six months older age (odds ratio (OR)
      9.4), low education (OR 14.7), and territorial infarct (OR 10.6) predicted
      dementia; and at 12 months low education (OR 8.7) and pre-stroke cerebrovascular
      damage (OR 7.4) predicted dementia. Predictors of VCI were low education (OR 3.4)
      and territorial infarct (OR 2.4) at one month post stroke; older age (OR 4.3) and
      low education (OR 4.1) at six months; and older age (OR 3.5) at 12 months.
      Predictors of vascular MCI were low education (OR 4.96) and territorial infarct
      (OR 3.58) at one month; and older age and lower education at six months (OR 3.4
      and 3.7, respectively) and at 12 months (OR 3.5 and 2.28, respectively).
      CONCLUSIONS: Territorial infarct, older age, and low educational level are
      predictors of cognitive disorders after stroke.

PMID- 15489390
TI  - A note on Pierre Marie (1853-1940).

PMID- 15489389
TI  - Post-stroke movement disorders: report of 56 patients.
AB  - BACKGROUND: Although movement disorders that occur following a stroke have long
      been recognised in short series of patients, their frequency and clinical and
      imaging features have not been reported in large series of patients with stroke.
      METHODS: We reviewed consecutive patients with involuntary abnormal movements
      (IAMs) following a stroke who were included in the Eugenio Espejo Hospital Stroke
      Registry and they were followed up for at least one year after the onset of the
      IAM. We determined the clinical features, topographical correlations, and
      pathophysiological implications of the IAMs. RESULTS: Of 1500 patients with
      stroke 56 developed movement disorders up to one year after the stroke. Patients
      with chorea were older and the patients with dystonia were younger than the
      patients with other IAMs. In patients with isolated vascular lesions without
      IAMs, surface lesions prevailed but patients with deep vascular lesions showed a
      higher probability of developing abnormal movements. One year after onset of the
      IAMs, 12 patients (21.4%) completely improved their abnormal movements, 38
      patients (67.8%) partially improved, four did not improve (7.1%), and two
      patients with chorea died. In the nested case-control analysis, the patients with
      IAMs displayed a higher frequency of deep lesions (63% v 33%; OR 3.38, 95% CI
      1.64 to 6.99, p<0.001). Patients with deep haemorrhagic lesions showed a higher
      probability of developing IAMs (OR 4.8, 95% CI 0.8 to 36.6). CONCLUSIONS: Chorea
      is the commonest movement disorder following stroke and appears in older
      patients. Involuntary movements tend to persist despite the functional recovery
      of motor deficit. Deep vascular lesions are more frequent in patients with
      movement disorders.

PMID- 15489391
TI  - Inappropriate emergency management of status epilepticus in children contributes
      to need for intensive care.
AB  - OBJECTIVES: To characterise the clinical features, emergency pre-paediatric
      intensive care (PIC) treatment, and course of status epilepticus (SE) in children
      admitted to PIC. This may provide insight into reasons for admission to PIC and
      provide a framework for the development of strategies that decrease the
      requirement for intensive care. DESIGN: Cross sectional, retrospective study.
      SETTING: A tertiary paediatric institution's intensive care unit. PARTICIPANTS:
      The admission database and all discharge summaries of each admission to a
      tertiary paediatric institution's PIC over a three year period were searched for
      children aged between 29 days and 15 years with a diagnosis of SE or related
      diagnoses. The case notes of potential cases of SE were systematically reviewed,
      and clinical and demographic data extracted using a standard data collection
      form. RESULTS: Most children with SE admitted to PIC are aged less than 5 years,
      male to female ratio 1:1, and most (77%) will have had no previous episodes of
      SE. Prolonged febrile convulsions, SE related to central nervous system
      infection, and SE associated with epilepsy occur in similar proportions. Contrary
      to the Advanced Paediatric Life Support guidelines many children admitted to PIC
      for SE receive over two doses, or inadequate doses, of benzodiazepine. There is a
      risk of respiratory depression following administration of over two doses of
      benzodiazepine (chi2 = 3.4, p = 0.066). Children with SE admitted to PIC who had
      prehospital emergency treatment are more likely to receive over two doses of
      benzodiazepines (chi2 = 11.5, p = 0.001), and to subsequently develop respiratory
      insufficiency (chi2 = 6.2, p = 0.01). Mortality is low. Further study is required
      to determine the morbidity associated with SE in childhood requiring intensive
      care. CONCLUSIONS: As the risk of respiratory depression is greater with more
      than two doses of benzodiazepines, clinicians should not disregard prehospital
      treatment of SE. As pre-PIC treatment of SE is inadequate in many cases,
      appropriate audit and modifications of standard guidelines are required.

PMID- 15489393
TI  - A cross sectional study on determinants of quality of life in ALS.
AB  - BACKGROUND: Understanding the determinants of quality of life (QoL) in
      amyotrophic lateral sclerosis (ALS) has become increasingly important with the
      recent emphasis on the comprehensive management of patients. OBJECTIVE: To
      evaluate the determinants of QoL in ALS using two scales with different
      theoretical constructs: the Schedule for the Evaluation of QoL-Direct Weighting
      (SEIQoL-DW), which evaluates subjective aspects of QoL, and the McGill QoL
      Questionnaire (MQOL), which evaluates both health related and non-health related
      factors of QoL. METHODS: Eighty consecutive patients with ALS underwent a battery
      of tests evaluating QoL and a series of physical, emotional, psychological, and
      socioeconomic predictor variables. A stepwise linear regression model was used to
      compare QoL scores and explicatory variables. RESULTS: SEIQoL-DW score was
      related to social support, depression, religiosity, and socioeconomic status.
      Total MQOL score was related to social support, socioeconomic status, and
      clinical status. MQOL single item score (MQOL-SIS) was related to social support,
      depression, social withdrawal, and socioeconomic status. SEIQoL-DW score was not
      related to total MQOL score. Conversely, a significant correlation was found
      between SEIQoL-DW and MQOL-SIS. CONCLUSIONS: With both QoL scales, the most
      important explicatory variable of QoL was the self perceived quality of social
      support. Physical status was not relevant in determining QoL. This study
      indicates that health related QoL measures are not adequate to assess QoL in
      patients with ALS, because their appreciation of QoL mainly relies on
      psychological, supportive, and spiritual factors. Therapeutic interventions
      should consider the psychological needs of patients and pay greater attention to
      caregivers' issues.

PMID- 15489392
TI  - Lesional mesial temporal lobe epilepsy and limited resections: prognostic factors
      and outcome.
AB  - OBJECTIVES: To evaluate the influence of clinical, investigational, surgical, and
      histopathological factors on postoperative seizure relief in patients with mesial
      temporal lobe epilepsy (MTLE) due to lesions other than ammonshornsclerosis
      (AHS). METHODS: Of 738 patients operated for TLE, 78 patients underwent limited
      resections for lesional MTLE (1990-2000). Seventy four patients with a follow up
      of more than one year were included. The preoperative clinical,
      neuropsychological, electroencephalogram, and neuroimaging characteristics were
      prospectively collected in a database. The histopathological material was re
      examined. RESULTS: The mean follow up was 49 months. Fifty eight patients were
      classified as seizure free (78.4% Class I), and six as almost seizure free (8.1%
      Class II), grouped together as satisfactory seizure control (64 patients, 86.5%).
      Five patients (6.8%) were categorised in Classes III and IV, respectively. These
      were grouped as unsatisfactory seizure control (10 patients, 13.5%). Surgical
      procedures were: 32 amygdalohippocampectomies (AH), 17 partial anterior AH, 15 AH
      plus polar resection, seven AH plus basal resection, and three AH plus extended
      temporal lesionectomy. There was no mortality and 2.7% mild permanent morbidity.
      Seizure relief did neither differ significantly with these approaches, nor with
      different classes of pathological findings (43 developmental tumours, 12 glial
      tumours, 10 dysplasias, and nine others). Even operation of dysplasias resulted
      in 80% satisfactory seizure control. Seizure onset during childhood proved to be
      a negative predictor for seizure relief (p = 0.020). MRI revealed 73 suspected
      lesions (98.6%), one dysembryoplastic neuroepithelial tumour was missed, in four
      cases no structural abnormalities could be confirmed with histopathological exam.
      Additionally, multifactorial regression revealed the factors "seizure onset after
      10 years of age", "presence of complex partial seizures", "absence of a
      neurological deficit", and a "correlating neuropsychological deficit" as
      predictive for satisfactory seizure control. CONCLUSIONS: "Preoperative
      tailoring" resulting in limit resections has proven to be safe and to provide a
      very good chance for satisfactory seizure relief in patients with lesional MTLE.

PMID- 15489394
TI  - Effects of lesions of the human posterior thalamus on ocular fixation during
      voluntary and visually triggered saccades.
AB  - OBJECTIVE: To investigate the role of the posterior thalamus in controlling
      voluntary and visually triggered eye movements and ocular fixation. METHODS: The
      latency to initiate saccades to peripheral targets (visually triggered) and in
      response to verbal commands (voluntary) was measured in three patients with
      unilateral lesions of the posterior thalamus, in normal controls, and in
      neurological controls with Parkinson's disease. On half the trials a fixation
      point offset simultaneously with target onset, and on half it remained visible.
      RESULTS: Offset of the fixation point simultaneous with target onset decreased
      saccade latency for both voluntary and visually triggered eye movements in
      controls, but only for voluntary saccades in patients with thalamic lesions.
      CONCLUSIONS: These findings suggest that separate neural systems control fixation
      when making voluntary and visually triggered eye movements, and that the thalamus
      is involved in the control of fixation for visually triggered but not for
      voluntary saccades.

PMID- 15489395
TI  - Unilateral calf hypertrophy.

PMID- 15489397
TI  - Cerebral atrophy in myotonic dystrophy: a voxel based morphometric study.
AB  - Brain involvement in myotonic dystrophy type 1 (DM1) is characterised by cortical
      atrophy and white matter lesions. We compared the magnetic resonance imaging
      derived grey matter maps of 22 DM1 patients with those of matched, healthy
      controls using voxel based morphometry to evaluate the extension of global and
      regional cortical atrophy in DM1, as well as its relationships with clinical and
      genetic features. Patients had significantly reduced brain tissue volumes. Grey
      matter volume was inversely correlated with age; this inverse correlation was
      significantly stronger in DM1 than in controls. Neither the clinical and genetic
      characteristics nor white matter lesions were correlated with cortical atrophy.
      Grey matter atrophy was located mainly in the bilateral frontal and parietal
      lobes, in the bilateral middle temporal gyrus, and in the left superior temporal
      and occipital gyrus.

PMID- 15489396
TI  - Frontotemporal dementia: impact of P301L tau mutation on a healthy carrier.
AB  - Frontotemporal dementia (FTD) is the second commonest form of dementia after
      Alzheimer's disease, but its clinical and biological features are less well
      known. To uncover its earliest signs, we studied the main clinical, neuroimaging,
      and biochemical findings in an asymptomatic carrier from a three generation FTD
      family, bearing the P301L pathogenic mutation in the tau gene. Except for
      selective impairment on the Verbal Fluency Test for letters, all cognitive tests
      were normal. The brain computed tomography scan was normal, but the brain single
      photon emission computed tomography and statistical parametric mapping (SPECT
      SPM) scan revealed bilateral frontal lobe hypoperfusion. Levels of total tau,
      181P-tau, and Abeta1-42 in the cerebrospinal fluid were increased compared with
      control values. We conclude that detection of these distinctive abnormalities
      should improve early diagnostic accuracy for FTD and help distinguish it from
      Alzheimer's disease.

PMID- 15489398
TI  - Meningeal derived cerebrospinal fluid proteins in different forms of dementia: is
      a meningopathy involved in normal pressure hydrocephalus?
AB  - OBJECTIVES: In animal models and in vitro studies leptomeninges have been shown
      to be the origin of neurotrophic substances that support the survival and growth
      of neuronal cells. Because dementia is associated with neuronal loss, we
      investigated whether leptomeningeal dysfunction may be involved in the
      pathogenesis of dementia disorders. METHODS: We analysed the cerebrospinal fluid
      (CSF) concentrations of the leptomeningeal derived beta trace protein, beta2
      microglobulin, and cystatin C. RESULTS: There was a statistically significant
      difference of the CSF beta trace protein levels among different groups. Patients
      with idiopathic normal pressure hydrocephalus (NPH) (17.5 (SD 4.3) mg/l) showed
      significantly lower CSF beta trace protein levels than patients with Alzheimer's
      disease (23.8 (6.2) mg/l), depression (24.2 (7.3) mg/l), and normal controls
      (25.3 (4.9) mg/l). To patients with vascular dementia (20.1 (5.6) mg/l) and
      frontotemporal dementia (21.9 (7.0) mg/l), the difference was not significant.
      There was no significant difference regarding the CSF and serum concentrations of
      beta2 microglobulin or cystatin C among the different groups. CONCLUSIONS: We
      conclude that leptomeningeal dysfunction may be involved in certain types of
      dementia such as NPH and that reduced CSF beta trace protein levels in patients
      with NPH may aid in differentiating this difficult to diagnose disorder from
      other syndromes such as Alzheimer's disease.

PMID- 15489399
TI  - Pathophysiology of parkinsonism due to hydrocephalus.
AB  - We report a patient with hydrocephalus who developed levodopa responsive
      parkinsonism and severe bradyphrenia associated with shunt malfunction and
      revision. Magnetic resonance imaging revealed periaqueductal edema involving
      medial substantia nigra. [18F]dopa positron emission tomography demonstrated
      reduced uptake in the caudate and putamen with relative sparing of the posterior
      putamen. Hydrocephalus associated with shunt malfunction can cause a distinct
      parkinsonian syndrome with greater dysfunction of projections from the medial
      substantia nigra to anterior striatum than in idiopathic Parkinson's disease.

PMID- 15489400
TI  - Late epilepsy following open surgery for aneurysmal subarachnoid haemorrhage.
AB  - OBJECTIVE: To determine the risk for late epilepsy (>2 weeks postoperatively)
      following aneurysmal subarachnoid haemorrhage (SAH) treated by early aneurysm
      clipping. DESIGN: Subgroup analysis of the East Anglian regional audit of SAH
      (1994-2000; n = 872) with 12 month follow up. Prophylactic anticonvulsants were
      not routinely prescribed unless there was a perioperative seizure. SUBJECTS: 472
      patients with aneurysmal SAH undergoing surgical clipping of the aneurysm were
      studied. Patients presenting in WFNS grade V, with space occupying haematomas
      requiring emergency surgery, or with posterior circulation aneurysms, rebleeds,
      and surgery after 21 days were excluded. RESULTS: Late epilepsy occurred in 23
      patients (4.9%). There was a correlation between the incidence of late epilepsy
      and both the presenting WFNS grade (p<0.05) (grade 1, 1.4%; grade 2, 3.8%; grade
      3, 9.6%; grade 4, 12.5%) and the Glasgow outcome score at discharge (p<0.01)
      (good recovery, 2.2%; moderate disability, 5.0%; severe disability, 15.5%). There
      was no relation between the incidence of late epilepsy and sex or the site of the
      aneurysm. CONCLUSIONS: The low incidence of late epilepsy following open surgery
      for aneurysmal SAH supports the withholding of prophylactic anticonvulsants.
      Patients with poor WFNS grade and poor recovery after surgery are at increased
      risk and should be closely monitored.

PMID- 15489401
TI  - Visual disturbances representing occipital lobe epilepsy in patients with
      cerebral calcifications and coeliac disease: a case series.
AB  - Paroxysmal visual manifestations may represent epileptic seizures arising from
      the occipital lobe. In coeliac disease (CD) bilateral occipital calcifications
      and seizure semiology consistent with an occipital origin have been described,
      primarily in Mediterranean countries. By reporting three adult patients from an
      Australian outpatient clinic with visual disturbances, occipital cerebral
      calcifications, and CD, this study seeks to emphasise that CD should be
      considered even when patients of non-Mediterranean origin present with these
      symptoms. Seizure types included simple partial, complex-partial, and secondarily
      generalised seizures. The seizure semiology consisted of visual disturbances such
      as: blurred vision, loss of focus, seeing coloured dots, and brief stereotyped
      complex visual hallucinations like seeing unfamiliar faces or scenes. Symptoms of
      malabsorption were not always present. Neurological examination was unremarkable
      in two patients, impaired dexterity and mild hemiatrophy on the left was noted in
      one. Routine electroencephalography was unremarkable. In all cases, computed
      tomography demonstrated bilateral cortical calcification of the occipital
      parietal regions. Magnetic resonance imaging showed no additional lesion. All
      patients had biopsy confirmed CD. Seizure control improved after treatment with
      gluten free diet and anticonvulsants. This report illustrates the association
      between seizures of occipital origin, cerebral calcifications, and CD even in
      patients not of Mediterranean origin.

PMID- 15489402
TI  - Illusory movements of the contralesional hand in patients with body image
      disorders.
AB  - OBJECTIVES: In the present study, we assess whether illusory sensations of
      movement can be elicited in patients with right brain damage (RBD). METHODS: Ten
      RBD patients (three with disorders of bodily representations) were asked to
      report whether movements of their right hand induced any illusory somatic or
      motor sensations. Inquiries on anomalous sensation of movement of the left hand
      were carried out while subjects: 1) observed the moving hand in a mirror propped
      vertically along the parasagittal plane; 2) looked directly at the moving hand;
      3) looked at the still hand; 4) kept their eyes closed. Twelve healthy subjects
      served as controls. RESULTS: Movement of the right hand induced a very clear
      sensation of movement of the left, contralesional hand in two patients affected
      by body image disorders. Remarkably, this occurred mainly while subjects were
      looking in the mirror, that is, when conflicts between visual, somatic, and motor
      information were maximal. In no condition did control subjects report any
      consistent anomalous evoked movement or sensation. CONCLUSIONS: Illusory
      movements of the left, plegic hand contingent upon sensorimotor conflicts can be
      evoked in brain damaged patients with body image disorders.

PMID- 15489403
TI  - Hereditary neuropathy with liability to pressure palsy: fulminant development
      with axonal loss during military training.
AB  - Hereditary neuropathy with liability to pressure palsy (HNPP) is characterised by
      recurrent mononeuropathies following minor trauma. We describe a case of
      fulminant HNPP beginning on the first day of military physical training.
      Protracted weakness, muscle atrophy, hand contractures, and multifocal sensory
      loss developed during a further three weeks of basic training. Nerve conduction
      changes were typical of HNPP, but without segmental slowing.
      Electromyographically, there was prominent acute denervation in muscles of the
      hands and right shoulder. Sural nerve biopsy demonstrated tomaculae and
      remyelination. Genetic testing revealed PMP-22 gene deletion. This case report
      demonstrates that HNPP can present with rapidly progressive peripheral nerve
      dysfunction and electrophysiological evidence of focal axonal loss.

PMID- 15489404
TI  - Effects of dexamethasone on peritumoural oedematous brain: a DT-MRI study.
AB  - OBJECTIVES: Glucocorticoids (dexamethasone) are thought to reduce peritumoural
      brain oedema by decreasing the permeability of neoplastic capillaries and/or
      enhancing the clearance of extracellular water. Diffusion tensor magnetic
      resonance imaging (DT-MRI) was used to measure the water diffusion parameters of
      oedematous and normal brain in a group of patients with intracranial tumours
      before and after steroid treatment. METHODS: Fifteen patients with intracranial
      tumours (seven with high-grade glioma, four with metastatic carcinoma and four
      with meningioma) were examined before and 48-72 h after dexamethasone treatment
      (16 mg/day). The mean diffusivity (<D>) and fractional anisotropy (FA) were
      measured for oedematous brain and apparently normal contralateral white matter
      before and after steroid therapy. RESULTS: In all three patient groups there was
      a significant decrease in <D> of oedematous brain after steroid treatment
      (p<0.01). There was no significant change in FA of oedematous brain after
      treatment in any of the three groups. There was also no significant change in
      either <D> or FA of apparently normal contralateral white matter after treatment.
      CONCLUSION: These data indicate that dexamethasone produces a localised reduction
      in the magnitude of extracellular water molecule mobility, and hence water
      content, in peritumoural oedematous brain. Furthermore, the magnitude of these
      changes is similar for both intra- and extra-axial tumours.

PMID- 15489405
TI  - Intramedullary tuberculoma mimicking primary CNS lymphoma.
AB  - The incidence of primary central nervous system lymphoma (PCNSL) has been on the
      rise in the setting of immunodeficiency syndromes such as acquired immune
      deficiency syndrome (AIDS). Its diagnosis has been facilitated by the advent of a
      cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) PCR assay. The reported high
      sensitivity and specificity of this assay has made it the cornerstone of
      diagnosis of PCNSL, replacing more traditional methods such as an open CNS
      biopsy. Here, we have described a patient with a known history of C3 AIDS
      presenting with lower extremity weakness and eventual myelopathy who was later
      diagnosed as having intramedullary PCNSL after detection of EBV DNA in his CSF.
      After failing to respond to radiotherapy, he underwent a spinal cord biopsy
      revealing intramedullary tuberculoma. This case illustrates the risk of
      misdiagnosis with this assay and the importance of histological confirmation of a
      pathological lesion prior to implementation of therapy.

PMID- 15489406
TI  - Intracranial dural arteriovenous fistulas with or without cerebral sinus
      thrombosis: analysis of 69 patients.
AB  - OBJECTIVES: To compare the characteristics of dural arteriovenous fistulas (AVFs)
      with or without cerebral sinus thrombosis (CST), and to analyse the determinants
      of aggressive manifestations in patients with dural AVF. METHODS: We investigated
      69 patients aged 51.4 (SD 15) years who were diagnosed as having dural AVF.
      According to the location of the lesion and venous drainage pattern, dural AVF
      was classified into three sites (cavernous sinus, large sinus, and other) and
      five types (by Cognard's method). Aggressive manifestations of dural AVF were
      defined as intracranial haemorrhage, venous infarction, seizure, altered mental
      status, and intracranial hypertension. The diagnosis of CST was based on cerebral
      angiography. Logistic regression methods were used to analyse the determinants of
      aggressive manifestation in patients with dural AVF. RESULTS: CST was found in
      39% of the patients with dural AVF. It was located at almost either the sinus
      around the dural AVF or the downstream venous flow pathways of the dural AVF.
      There was no significant difference with regard to sex, location, or type of
      dural AVF between patients with dural AVF with and without CST. The location
      "other sinuses" and the type of dural AVF "IIb/IIa+b/III/IV/V" were significantly
      related to aggressive manifestations of dural AVF (odds ratio 19 (p = 0.001) and
      5.63 (p = 0.033), respectively). Presence of CST in patients with dural AVF had
      an odds ratio of 4.25 (p = 0.12) for development of aggressive manifestations.
      CONCLUSIONS: CST affects two fifths of patients with dural AVF. The location and
      type of dural AVF are major determinants of aggressive manifestations in patients
      with dural AVF.

PMID- 15489407
TI  - Electro-oculographic measures in patients with chronic whiplash and healthy
      subjects: a comparative study.
AB  - BACKGROUND: Despite their high incidence, costs, and long lasting disability,
      whiplash associated disorders (WAD) lack an identifiable objective pathology that
      explains their acute or chronic symptoms. OBJECTIVE: In view of previous
      suggestions of a possible effect of neck torsion on several electro-oculography
      (EOG) parameters, the main objective of this study was to examine their
      applicability in differentiating patients from uninvolved subjects. METHODS:
      Smooth pursuit and saccadic eye movements were assessed in 26 patients with
      chronic WAD and 23 healthy subjects. All tests were executed in three neck
      positions: neutral and rotations to left and right. RESULTS: Neck torsion did not
      influence eye movement performance of either the WAD or healthy groups. However,
      compared with the healthy group, patients with WAD had significantly lower smooth
      pursuit velocity gain (SPVG) (p = 0.01) and prolonged saccadic latency (p =
      0.001), irrespective of neck position. CONCLUSIONS: Despite scattered differences
      that reached significance, the electro-oculographic measures used in this study
      do not seem to offer a clinically relevant method for differentiating between
      patients with WAD and normal subjects.

PMID- 15489408
TI  - Multiple painful sensory mononeuropathies (MPSM), a novel pattern of sarcoid
      neuropathy.

PMID- 15489409
TI  - Non-herpetic limbic encephalitis associated with relapsing polychondritis.

PMID- 15489410
TI  - Diffusion tensor MRI of the cervical cord in a patient with syringomyelia and
      multiple sclerosis.

PMID- 15489411
TI  - Epilepsy in one family with parietal foramina: an incidental finding?

PMID- 15489412
TI  - Ipsilateral axial lateropulsion as an initial symptom of vertebral artery
      occlusion.

PMID- 15489413
TI  - Baroreflex failure secondary to paraneoplastic encephalomyelitis in a 17 year old
      woman with neuroblastoma.

PMID- 15489414
TI  - Acquired ocular motor apraxia from bilateral frontoparietal infarcts associated
      with Takayasu arteritis.

PMID- 15489415
TI  - Bacteriophage P1 in retrospect and in prospect.

PMID- 15489416
TI  - Phage taxonomy: we agree to disagree.

PMID- 15489418
TI  - Lactobacillus plantarum bacteriophage LP65: a new member of the SPO1-like genus
      of the family Myoviridae.
AB  - The virulent Lactobacillus plantarum myophage LP65 was isolated from industrial
      meat fermentation. Tail contraction led to reorganization of the tail sheath and
      the baseplate; a tail tube was extruded. In ultrathin section the phage adsorbed
      via its baseplate to the exterior of the cell, while the tail tube tunneled
      through the thick bacterial cell wall. Convoluted membrane structures were
      induced in the infected cell. Progeny phage was detected 100 min postinfection,
      and lysis occurred after extensive digestion of the cell wall. Sequence analysis
      revealed a genome of 131,573 bp of nonredundant DNA. Four major genome regions
      and a large tRNA gene cluster were observed. One module corresponded to DNA
      replication genes. Helicase/primase and two replication/recombination enzymes
      represented the only links to T4-like Myoviridae from gram-negative bacteria.
      Another module corresponded to the structural genes. Sequence relatedness
      identified links with Listeria phage A511, Staphylococcus phage K, and Bacillus
      phage SPO1. LP65 structural proteins were identified by two-dimensional proteome
      analysis and mass spectrometry. The putative tail sheath protein showed a shear
      induced change in electrophoretic migration behavior. The genome organization of
      the structural module in LP65 resembled that of Siphoviridae from the lambda
      supergroup.

PMID- 15489419
TI  - Multicopy plasmids affect replisome positioning in Bacillus subtilis.
AB  - The DNA replication machinery, various regions of the chromosome, and some
      plasmids occupy characteristic subcellular positions in bacterial cells. We
      visualized the location of a multicopy plasmid, pHP13, in living cells of
      Bacillus subtilis using an array of lac operators and LacI-green fluorescent
      protein (GFP). In the majority of cells, plasmids appeared to be highly mobile
      and randomly distributed. In a small fraction of cells, there appeared to be
      clusters of plasmids located predominantly at or near a cell pole. We also
      monitored the effects of the presence of multicopy plasmids on the position of
      DNA polymerase using a fusion of a subunit of DNA polymerase to GFP. Many of the
      plasmid-containing cells had extra foci of the replisome, and these were often
      found at uncharacteristic locations in the cell. Some of the replisome foci were
      dynamic and highly mobile, similar to what was observed for the plasmid. In
      contrast, replisome foci in plasmid-free cells were relatively stationary. Our
      results indicate that in B. subtilis, plasmid-associated replisomes are recruited
      to the subcellular position of the plasmid. Extending this notion to the
      chromosome, we postulated that the subcellular position of the chromosomally
      associated replisome is established by the subcellular location of oriC at the
      time of initiation of replication.

PMID- 15489420
TI  - Rgg regulates growth phase-dependent expression of proteins associated with
      secondary metabolism and stress in Streptococcus pyogenes.
AB  - The transcriptional regulatory protein Rgg coordinates amino acid catabolism and
      virulence factor expression in Streptococcus pyogenes. We used a proteomic
      approach to compare cytoplasmic proteins isolated from S. pyogenes wild-type
      strain NZ131 (serotype M49) to proteins isolated from an rgg mutant strain during
      the exponential and stationary phases of growth. Proteins were separated by two
      dimensional gel electrophoresis, and 125 protein spots of interest were
      identified by tandem mass spectrometry. Comparative analysis of proteins isolated
      from the isogenic strains revealed that growth phase-associated regulation of
      enzymes involved in the metabolism of arginine (ArcABC), histidine (HutI), and
      serine (SdhA) was abrogated in the rgg mutant strain, which synthesized the
      proteins in the exponential phase of growth. In contrast, the enzymes were
      detected only among wild-type proteins isolated from organisms in the stationary
      phase of growth. The differences in protein composition were correlated with
      previously described metabolic changes. In addition, proteins associated with
      thermal and oxidative stress responses, including ClpE and ClpL, were present in
      samples isolated from the rgg mutant strain but not in samples isolated from the
      wild-type strain. The rgg mutant strain was more tolerant to elevated temperature
      and puromycin than the wild-type strain; however, the mutant was less tolerant to
      paraquat. We concluded that Rgg is a global regulatory factor that contributes to
      growth phase-dependent synthesis of proteins associated with secondary metabolism
      and oxidative and thermal stress responses.

PMID- 15489421
TI  - Four proteins encoded in the gspB-secY2A2 operon of Streptococcus gordonii
      mediate the intracellular glycosylation of the platelet-binding protein GspB.
AB  - Platelet binding by Streptococcus gordonii strain M99 is mediated predominantly
      by the cell surface glycoprotein GspB. This adhesin consists of a putative N
      terminal signal peptide, two serine-rich regions (SRR1 and SRR2), a basic region
      between SRR1 and SRR2, and a C-terminal cell wall anchoring domain. The
      glycosylation of GspB is mediated at least in part by Gly and Nss, which are
      encoded in the secY2A2 locus immediately downstream of gspB. This region also
      encodes two proteins (Gtf and Orf4) that are required for the expression of GspB
      but whose functions have not been delineated. In this study, we further
      characterized the roles of Gly, Nss, Gtf, and Orf4 by investigating the
      expression and glycosylation of a series of glutathione S-transferase-GspB fusion
      proteins in M99 and in gly, nss, gtf, and orf4 mutants. Compared with fusion
      proteins expressed in the wild-type background, fusion proteins expressed in the
      mutant strain backgrounds showed altered electrophoretic mobility. In addition,
      the fusion proteins formed insoluble aggregates in protoplasts of the gtf and
      orf4 mutants. Glycan detection and lectin blot analysis revealed that SRR1 and
      SRR2 were glycosylated but that the basic region was unmodified. When the fusion
      protein was expressed in Escherichia coli, glycosylation of this protein was
      observed only in the presence of both gtf and orf4. These results demonstrate
      that Gly, Nss, Gtf, and Orf4 are all involved in the intracellular glycosylation
      of SRRs. Moreover, Gtf and Orf4 are essential for glycosylation, which in turn is
      important for the solubility of GspB.

PMID- 15489417
TI  - Genome of bacteriophage P1.
AB  - P1 is a bacteriophage of Escherichia coli and other enteric bacteria. It
      lysogenizes its hosts as a circular, low-copy-number plasmid. We have determined
      the complete nucleotide sequences of two strains of a P1 thermoinducible mutant,
      P1 c1-100. The P1 genome (93,601 bp) contains at least 117 genes, of which almost
      two-thirds had not been sequenced previously and 49 have no homologs in other
      organisms. Protein-coding genes occupy 92% of the genome and are organized in 45
      operons, of which four are decisive for the choice between lysis and lysogeny.
      Four others ensure plasmid maintenance. The majority of the remaining 37 operons
      are involved in lytic development. Seventeen operons are transcribed from
      sigma(70) promoters directly controlled by the master phage repressor C1. Late
      operons are transcribed from promoters recognized by the E. coli RNA polymerase
      holoenzyme in the presence of the Lpa protein, the product of a C1-controlled P1
      gene. Three species of P1-encoded tRNAs provide differential controls of
      translation, and a P1-encoded DNA methyltransferase with putative bifunctionality
      influences transcription, replication, and DNA packaging. The genome is
      particularly rich in Chi recombinogenic sites. The base content and distribution
      in P1 DNA indicate that replication of P1 from its plasmid origin had more impact
      on the base compositional asymmetries of the P1 genome than replication from the
      lytic origin of replication.

PMID- 15489422
TI  - Classification and strength measurement of stationary-phase promoters by use of a
      newly developed promoter cloning vector.
AB  - When an Escherichia coli culture changes from exponential growth to the
      stationary phase, expression of growth-related genes levels off, while a number
      of stationary-phase-specific genes are turned on. To gain insight into the growth
      phase-dependent global regulation of genome transcription, we analyzed the
      strength and specificity of promoters associated with the stationary-phase genes.
      For the in vivo assay of promoter activity, 300- to 500-bp DNA fragments upstream
      from the translation initiation codon were isolated and inserted into a newly
      constructed doubly fluorescent protein (DFP) vector. The activity of test
      promoters was determined by measuring the green fluorescent protein (GFP). To
      avoid the possible influence of plasmid copy number, the level of transcription
      of reference promoter lacUV5 on the same plasmid was determined by measuring the
      red fluorescent protein (RFP). Thus, the activities of test promoters could be
      easily and accurately determined by determining the GFP/RFP ratio. Analysis of
      the culture time-dependent variation of 100 test promoters indicated that (i) a
      major group of the stationary-phase promoters are up-regulated only in the
      presence of RpoS sigma; (ii) the phase-coupled increase in the activity of some
      promoters takes place even in the absence of RpoS; and (iii) the activity of some
      promoters increases in the absence of RpoS. This classification was confirmed by
      testing in vitro transcription by using reconstituted RpoD and RpoS holoenzymes.

PMID- 15489423
TI  - The genome sequence of Mycoplasma hyopneumoniae strain 232, the agent of swine
      mycoplasmosis.
AB  - We present the complete genome sequence of Mycoplasma hyopneumoniae, an important
      member of the porcine respiratory disease complex. The genome is composed of
      892,758 bp and has an average G+C content of 28.6 mol%. There are 692 predicted
      protein coding sequences, the average protein size is 388 amino acids, and the
      mean coding density is 91%. Functions have been assigned to 304 (44%) of the
      predicted protein coding sequences, while 261 (38%) of the proteins are conserved
      hypothetical proteins and 127 (18%) are unique hypothetical proteins. There is a
      single 16S-23S rRNA operon, and there are 30 tRNA coding sequences. The cilium
      adhesin gene has six paralogs in the genome, only one of which contains the
      cilium binding site. The companion gene, P102, also has six paralogs. Gene
      families constitute 26.3% of the total coding sequences, and the largest family
      is the 34-member ABC transporter family. Protein secretion occurs through a
      truncated pathway consisting of SecA, SecY, SecD, PrsA, DnaK, Tig, and LepA. Some
      highly conserved eubacterial proteins, such as GroEL and GroES, are notably
      absent. The DnaK-DnaJ-GrpR complex is intact, providing the only control over
      protein folding. There are several proteases that might serve as virulence
      factors, and there are 53 coding sequences with prokaryotic lipoprotein lipid
      attachment sites. Unlike other mycoplasmas, M. hyopneumoniae contains few genes
      with tandem repeat sequences that could be involved in phase switching or
      antigenic variation. Thus, it is not clear how M. hyopneumoniae evades the immune
      response and establishes a chronic infection.

PMID- 15489424
TI  - Crystal structure of the YgfZ protein from Escherichia coli suggests a folate
      dependent regulatory role in one-carbon metabolism.
AB  - The ygfZ gene product of Escherichia coli represents a large protein family
      conserved in bacteria to eukaryotes. The members of this family are
      uncharacterized proteins with marginal sequence similarity to the T-protein
      (aminomethyltransferase) of the glycine cleavage system. To assist with the
      functional assignment of the YgfZ family, the crystal structure of the E. coli
      protein was determined by multiwavelength anomalous diffraction. The protein
      molecule has a three-domain architecture with a central hydrophobic channel. The
      structure is very similar to that of bacterial dimethylglycine oxidase, an enzyme
      of the glycine betaine pathway and a homolog of the T-protein. Based on
      structural superposition, a folate-binding site was identified in the central
      channel of YgfZ, and the ability of YgfZ to bind folate derivatives was confirmed
      experimentally. However, in contrast to dimethylglycine oxidase and T-protein,
      the YgfZ family lacks amino acid conservation at the folate site, which implies
      that YgfZ is not an aminomethyltransferase but is likely a folate-dependent
      regulatory protein involved in one-carbon metabolism.

PMID- 15489425
TI  - Tertiary structure of Staphylococcus aureus cell wall murein.
AB  - The recently described scaffold model of murein architecture depicts the gram
      negative bacterial cell wall as a gel-like matrix composed of cross-linked glycan
      strands oriented perpendicularly to the plasma membrane while peptide bridges
      adopt a parallel orientation (B. A. Dmitriev, F. V. Toukach, K. J. Schaper, O.
      Holst, E. T. Rietschel, and S. Ehlers, J. Bacteriol. 185:3458-3468, 2003). Based
      on the scaffold model, we now present computer simulation studies on the
      peptidoglycan arrangement of the gram-positive organism Staphylococcus aureus,
      which show that the orientation of peptide bridges is critical for the highly
      cross-linked murein architecture of this microorganism. According to the proposed
      refined model, staphylococcal murein is composed of glycan and oligopeptide
      chains, both running in a plane that is perpendicular to the plasma membrane,
      with oligopeptide chains adopting a zigzag conformation and zippering adjacent
      glycan strands along their lengths. In contrast to previous models of murein in
      gram-positive bacteria, this model reflects the high degree of cross-linking that
      is the hallmark of the staphylococcal cell wall and is compatible with
      distinguishing features of S. aureus cytokinesis such as the triple consecutive
      alteration of the division plane orientation and the strictly centripetal mode of
      septum closure.

PMID- 15489426
TI  - Isolation of SOS constitutive mutants of Escherichia coli.
AB  - The bacterial SOS regulon is strongly induced in response to DNA damage from
      exogenous agents such as UV radiation and nalidixic acid. However, certain
      mutants with defects in DNA replication, recombination, or repair exhibit a
      partially constitutive SOS response. These mutants presumably suffer frequent
      replication fork failure, or perhaps they have difficulty rescuing forks that
      failed due to endogenous sources of DNA damage. In an effort to understand more
      clearly the endogenous sources of DNA damage and the nature of replication fork
      failure and rescue, we undertook a systematic screen for Escherichia coli mutants
      that constitutively express the SOS regulon. We identified mutant strains with
      transposon insertions in 42 genes that caused increased expression from a
      dinD1::lacZ reporter construct. Most of these also displayed significant
      increases in basal levels of RecA protein, confirming an effect on the SOS
      system. As expected, this collection includes genes, such as lexA, dam, rep,
      xerCD, recG, and polA, which have previously been shown to cause an SOS
      constitutive phenotype when inactivated. The collection also includes 28 genes or
      open reading frames that were not previously identified as SOS constitutive,
      including dcd, ftsE, ftsX, purF, tdcE, and tynA. Further study of these SOS
      constitutive mutants should be useful in understanding the multiple causes of
      endogenous DNA damage. This study also provides a quantitative comparison of the
      extent of SOS expression caused by inactivation of many different genes in a
      common genetic background.

PMID- 15489427
TI  - The completely sequenced plasmid pEST4011 contains a novel IncP1 backbone and a
      catabolic transposon harboring tfd genes for 2,4-dichlorophenoxyacetic acid
      degradation.
AB  - The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D)-degrading bacterium
      Achromobacter xylosoxidans subsp. denitrificans strain EST4002 contains plasmid
      pEST4011. This plasmid ensures its host a stable 2,4-D(+) phenotype. We
      determined the complete 76,958-bp nucleotide sequence of pEST4011. This plasmid
      is a deletion and duplication derivative of pD2M4, the 95-kb highly unstable
      laboratory ancestor of pEST4011, and was self-generated during different
      laboratory manipulations performed to increase the stability of the 2,4-D(+)
      phenotype of the original strain, strain D2M4(pD2M4). The 47,935-bp catabolic
      region of pEST4011 forms a transposon-like structure with identical copies of the
      hybrid insertion element IS1071::IS1471 at the two ends. The catabolic regions of
      pEST4011 and pJP4, the best-studied 2,4-D-degradative plasmid, both contain
      homologous, tfd-like genes for complete 2,4-D degradation, but they have little
      sequence similarity other than that. The backbone genes of pEST4011 are most
      similar to the corresponding genes of broad-host-range self-transmissible IncP1
      plasmids. The backbones of the other three IncP1 catabolic plasmids that have
      been sequenced (the 2,4-D-degradative plasmid pJP4, the haloacetate-catabolic
      plasmid pUO1, and the atrazine-catabolic plasmid pADP-1) are nearly identical to
      the backbone of R751, the archetype plasmid of the IncP1 beta subgroup. We show
      that despite the overall similarity in plasmid organization, the pEST4011
      backbone is sufficiently different (51 to 86% amino acid sequence identity
      between individual backbone genes) from the backbones of members of the three
      IncP1 subgroups (the alpha, beta, and gamma subgroups) that it belongs to a new
      IncP1subgroup, the delta subgroup. This conclusion was also supported by a
      phylogenetic analysis of the trfA2, korA, and traG gene products of different
      IncP1 plasmids.

PMID- 15489428
TI  - The N terminus of MinD contains determinants which affect its dynamic
      localization and enzymatic activity.
AB  - MinD is involved in regulating the proper placement of the cytokinetic machinery
      in some bacteria, including Neisseria gonorrhoeae and Escherichia coli.
      Stimulation of the ATPase activity of MinD by MinE has been proposed to induce
      dynamic, pole-to-pole oscillations of MinD in E. coli. Here, we investigated the
      effects of deleting or mutating conserved residues within the N terminus of N.
      gonorrhoeae MinD (MinD(Ng)) on protein dynamism, localization, and interactions
      with MinD(Ng) and with MinE(Ng). Deletions or mutations were generated in the
      first five residues of MinD(Ng), and mutant proteins were evaluated by several
      functional assays. Truncation or mutation of N-terminal residues disrupted
      MinD(Ng) interactions with itself and with MinE. Although the majority of green
      fluorescent protein (GFP)-MinD(Ng) mutants could still oscillate from pole to
      pole in E. coli, the GFP-MinD(Ng) oscillation cycles were significantly faster
      and were accompanied by increased cytoplasmic localization. Interestingly, in
      vitro ATPase assays indicated that MinD(Ng) proteins lacking the first three
      residues or with an I5E substitution possessed higher MinE(Ng)-independent ATPase
      activities than the wild-type protein. These results indicate that determinants
      found within the extreme N terminus of MinD(Ng) are implicated in regulating the
      enzymatic activity and dynamic localization of the protein.

PMID- 15489429
TI  - SigmaS-dependent gene expression at the onset of stationary phase in Escherichia
      coli: function of sigmaS-dependent genes and identification of their promoter
      sequences.
AB  - The sigma(S) subunit of RNA polymerase, the product of the rpoS gene, controls
      the expression of genes responding to starvation and cellular stresses. Using
      gene array technology, we investigated rpoS-dependent expression at the onset of
      stationary phase in Escherichia coli grown in rich medium. Forty-one genes were
      expressed at significantly lower levels in an rpoS mutant derived from the MG1655
      strain; for 10 of these, we also confirmed rpoS and stationary-phase dependence
      by reverse transcription-PCR. Only seven genes (dps, osmE, osmY, sodC, rpsV,
      wrbA, and yahO) had previously been recognized as rpoS dependent. Several newly
      identified rpoS-dependent genes are involved in the uptake and metabolism of
      amino acids, sugars, and iron. Indeed, the rpoS mutant strain shows severely
      impaired growth on some sugars such as fructose and N-acetylglucosamine. The rpoS
      gene controls the production of indole, which acts as a signal molecule in
      stationary-phase cells, via regulation of the tnaA-encoded tryptophanase enzyme.
      Genes involved in protein biosynthesis, encoding the ribosome-associated protein
      RpsV (sra) and the initiation factor IF-1 (infA), were also induced in an rpoS
      dependent fashion. Using primer extension, we determined the promoter sequences
      of a selection of rpoS-regulated genes representative of different functional
      classes. Significant fractions of these promoters carry sequence features
      specific for Esigma(S) recognition of the -10 region, such as cytosines at
      positions -13 (70%) and -12 (30%) as well as a TG motif located upstream of the 
      10 region (50%), thus supporting the TGN(0-2)C(C/T)ATA(C/A)T consensus sequence
      recently proposed for sigma(S).

PMID- 15489430
TI  - Characterization of the Escherichia coli AaeAB efflux pump: a metabolic relief
      valve?
AB  - Treatment of Escherichia coli with p-hydroxybenzoic acid (pHBA) resulted in
      upregulation of yhcP, encoding a protein of the putative efflux protein family.
      Also upregulated were the adjacent genes yhcQ, encoding a protein of the membrane
      fusion protein family, and yhcR, encoding a small protein without a known or
      suggested function. The function of the upstream, divergently transcribed gene
      yhcS, encoding a regulatory protein of the LysR family, in regulating expression
      of yhcRQP was shown. Furthermore, it was demonstrated that several aromatic
      carboxylic acid compounds serve as inducers of yhcRQP expression. The efflux
      function encoded by yhcP was proven by the hypersensitivity to pHBA of a yhcP
      mutant strain. A yhcS mutant strain was also hypersensitive to pHBA. Expression
      of yhcQ and yhcP was necessary and sufficient for suppression of the pHBA
      hypersensitivity of the yhcS mutant. Only a few aromatic carboxylic acids of
      hundreds of diverse compounds tested were defined as substrates of the YhcQP
      efflux pump. Thus, we propose renaming yhcS, yhcR, yhcQ, and yhcP, to reflect
      their role in aromatic carboxylic acid efflux, to aaeR, aaeX, aaeA, and aaeB,
      respectively. The role of pHBA in normal E. coli metabolism and the highly
      regulated expression of the AaeAB efflux system suggests that the physiological
      role may be as a "metabolic relief valve" to alleviate toxic effects of
      imbalanced metabolism.

PMID- 15489431
TI  - Membrane topology analysis of cyclic glucan synthase, a virulence determinant of
      Brucella abortus.
AB  - Brucella abortus cyclic glucan synthase (Cgs) is a 316-kDa (2,831-amino-acid)
      integral inner membrane protein that is responsible for the synthesis of cyclic
      beta-1,2-glucan by a novel mechanism in which the enzyme itself acts as a protein
      intermediate. B. abortus Cgs uses UDP-glucose as a sugar donor and has the three
      enzymatic activities necessary for synthesis of the cyclic polysaccharide (i.e.,
      initiation, elongation, and cyclization). Cyclic glucan is required in B. abortus
      for effective host interaction and complete expression of virulence. To gain
      further insight into the structure and mechanism of action of B. abortus Cgs, we
      studied the membrane topology of the protein using a combination of in silico
      predictions, a genetic approach involving the construction of fusions between the
      cgs gene and the genes encoding alkaline phosphatase (phoA) and beta
      galactosidase (lacZ), and site-directed chemical labeling of lysine residues. We
      found that B. abortus Cgs is a polytopic membrane protein with the amino and
      carboxyl termini located in the cytoplasm and with six transmembrane segments,
      transmembrane segments I (residues 419 to 441), II (residues 452 to 474), III
      (residues 819 to 841), IV (residues 847 to 869), V (residues 939 to 961), and VI
      (residues 968 to 990). The six transmembrane segments determine four large
      cytoplasmic domains and three very small periplasmic regions.

PMID- 15489433
TI  - MorA defines a new class of regulators affecting flagellar development and
      biofilm formation in diverse Pseudomonas species.
AB  - Assembly of bacterial flagella is developmentally important during both
      planktonic cell growth and biofilm formation. Flagellar biogenesis is complex,
      requiring coordinated expression of over 40 genes, and normally commences during
      the log-to-stationary transition phase. We describe here a novel membrane
      localized regulator, MorA, that controls the timing of flagellar development and
      affects motility, chemotaxis, and biofilm formation in Pseudomonas putida. MorA
      is conserved among diverse Pseudomonas species, and homologues are present in all
      Pseudomonas genomes sequenced thus far. In P. putida, the absence of MorA
      derepresses flagellar development, which leads to constitutive formation of
      flagella in the mutant cells in all growth phases. In Pseudomonas aeruginosa, the
      absence of MorA led to a reduction in biofilm formation. However, unlike the
      motility of P. putida, the motility of the P. aeruginosa mutants was unaffected.
      Our data illustrate a novel developmentally regulated sensory and signaling
      pathway for several properties required for virulence and ecological fitness of
      Pseudomonas species.

PMID- 15489432
TI  - Role of alpha-methylacyl coenzyme A racemase in the degradation of methyl
      branched alkanes by Mycobacterium sp. strain P101.
AB  - A new isolate, Mycobacterium sp. strain P101, is capable of growth on methyl
      branched alkanes (pristane, phytane, and squalane). Among ca. 10,000 Tn5-derived
      mutants, we characterized 2 mutants defective in growth on pristane or n
      hexadecane. A single copy of Tn5 was found to be inserted into the coding region
      of mcr (alpha-methylacyl coenzyme A [alpha-methylacyl-CoA] racemase gene) in
      mutant P1 and into the coding region of mls (malate synthase gene) in mutant H1.
      Mutant P1 could not grow on methyl-branched alkanes. The recombinant Mcr produced
      in Escherichia coli was confirmed to catalyze racemization of (R)-2
      methylpentadecanoyl-CoA, with a specific activity of 0.21 micromol . min(-1) . mg
      of protein(-1). Real-time quantitative reverse transcriptase PCR analyses
      indicated that mcr gene expression was enhanced by the methyl-branched alkanes
      pristane and squalane. Mutant P1 used (S)-2-methylbutyric acid for growth but did
      not use the racemic compound, and growth on n-hexadecane was not inhibited by
      pristane. These results suggested that the oxidation of the methyl-branched
      alkanoic acid is inhibited by the (R) isomer, although the (R) isomer was not
      toxic during growth on n-hexadecane. Based on these results, Mcr is suggested to
      play a critical role in beta-oxidation of methyl-branched alkanes in
      Mycobacterium. On the other hand, mutant H1 could not grow on n-hexadecane, but
      it partially retained the ability to grow on pristane. The reduced growth of
      mutant H1 on pristane suggests that propionyl-CoA is available for cell
      propagation through the 2-methyl citric acid cycle, since propionyl-CoA is
      produced through beta-oxidation of pristane.

PMID- 15489434
TI  - Ribose utilization with an excess of mutarotase causes cell death due to
      accumulation of methylglyoxal.
AB  - Methylglyoxal (MG) is a highly reactive metabolic intermediate, presumably
      accumulated during uncontrolled carbohydrate metabolism. The major source of MG
      is dihydroxyacetone phosphate, which is catalyzed by MG synthase (the mgs
      product) in bacteria. We observed Escherichia coli cell death when the ribose
      transport system, consisting of the RbsDACBK proteins, was overproduced on
      multicopy plasmids. Almost 100% of cell death occurs a few hours after ribose
      addition (>10 mM), due to an accumulation of extracellular MG as detected by (1)H
      nuclear magnetic resonance ((1)H-NMR). Under lethal conditions, the concentration
      of MG produced in the medium reached approximately 1 mM after 4 h of ribose
      addition as measured by high-performance liquid chromatography. An excess of the
      protein RbsD, recently characterized as a mutarotase that catalyzes the
      conversion between the beta-pyran and beta-furan forms of ribose, was critical in
      accumulating the lethal level of MG, which was also shown to require ribokinase
      (RbsK). The intracellular level of ribose 5-phosphate increased with the presence
      of the protein RbsD, as determined by (31)P-NMR. As expected, a mutation in the
      methylglyoxal synthase gene (mgs) abolished the production of MG. These results
      indicate that the enhanced ribose uptake and incorporation lead to an
      accumulation of MG, perhaps occurring via the pentose-phosphate pathway and via
      glycolysis with the intermediates fructose 6-phosphate and glyceraldehyde 3
      phosphate. It was also demonstrated that a small amount of MG is synthesized by
      monoamine oxidase.

PMID- 15489435
TI  - The Escherichia coli DjlA and CbpA proteins can substitute for DnaJ in DnaK
      mediated protein disaggregation.
AB  - The DnaJ (Hsp40) protein of Escherichia coli serves as a cochaperone of DnaK
      (Hsp70), whose activity is involved in protein folding, protein targeting for
      degradation, and rescue of proteins from aggregates. Two other E. coli proteins,
      CbpA and DjlA, which exhibit homology with DnaJ, are known to interact with DnaK
      and to stimulate its chaperone activity. Although it has been shown that in dnaJ
      mutants both CbpA and DjlA are essential for growth at temperatures above 37
      degrees C, their in vivo role is poorly understood. Here we show that in a dnaJ
      mutant both CbpA and DjlA are required for efficient protein dissaggregation at
      42 degrees C.

PMID- 15489436
TI  - The "intracellular" poly(3-hydroxybutyrate) (PHB) depolymerase of Rhodospirillum
      rubrum is a periplasm-located protein with specificity for native PHB and with
      structural similarity to extracellular PHB depolymerases.
AB  - Rhodospirillum rubrum possesses a putative intracellular poly(3-hydroxybutyrate)
      (PHB) depolymerase system consisting of a soluble PHB depolymerase, a heat-stable
      activator, and a 3-hydroxybutyrate dimer hydrolase (J. M. Merrick and M.
      Doudoroff, J. Bacteriol. 88:60-71, 1964). In this study we reinvestigated the
      soluble R. rubrum PHB depolymerase (PhaZ1). It turned out that PhaZ1 is a novel
      type of PHB depolymerase with unique properties. Purified PhaZ1 was specific for
      amorphous short-chain-length polyhydroxyalkanoates (PHA) such as native PHB,
      artificial PHB, and oligomer esters of (R)-3-hydroxybutyrate with 3 or more 3
      hydroxybutyrate units. Atactic PHB, (S)-3-hydroxybutyrate oligomers, medium-chain
      length PHA, and lipase substrates (triolein, tributyrin) were not hydrolyzed. The
      PHB depolymerase structural gene (phaZ1) was cloned. Its deduced amino acid
      sequence (37,704 Da) had no significant similarity to those of intracellular PHB
      depolymerases of Wautersia eutropha or of other PHB-accumulating bacteria. PhaZ1
      was found to have strong amino acid homology with type-II catalytic domains of
      extracellular PHB depolymerases, and Ser(42), Asp(138), and His(178) were
      identified as catalytic-triad amino acids, with Ser(42) as the putative active
      site. Surprisingly, the first 23 amino acids of the PHB depolymerase previously
      assumed to be intracellular revealed features of classical signal peptides, and
      Edman sequencing of purified PhaZ1 confirmed the functionality of the predicted
      cleavage site. Extracellular PHB depolymerase activity was absent, and analysis
      of cell fractions unequivocally showed that PhaZ1 is a periplasm-located enzyme.
      The previously assumed intracellular activator/depolymerase system is unlikely to
      have a physiological function in PHB mobilization in vivo. A second gene,
      encoding the putative true intracellular PHB depolymerase (PhaZ2), was identified
      in the genome sequence of R. rubrum.

PMID- 15489437
TI  - Osa protein constitutes a strong oncogenic suppression system that can block vir
      dependent transfer of IncQ plasmids between Agrobacterium cells and the
      establishment of IncQ plasmids in plant cells.
AB  - The osa (oncogenic suppressive activity) gene of the IncW group plasmid pSa is
      sufficient to suppress tumorigenesis by Agrobacterium tumefaciens. osa confers
      oncogenic suppression by inhibiting VirE2 protein export. This result is similar,
      but not identical, to that of oncogenic suppression by the IncQ plasmid RSF1010.
      We conducted a series of experiments to compare oncogenic suppression by these
      two systems. Agrobacterium strains harboring plasmids containing osa are more
      able to effect oncogenic suppression than are similar strains containing various
      RSF1010 derivatives. When osa is present within a donor Agrobacterium strain that
      also carries a derivative of RSF1010, the transfer of RSF1010 derivatives to
      recipient bacteria and their establishment in plants are blocked. Oncogenic
      suppression is still effected when the osa gene is integrated into the
      Agrobacterium chromosome, suggesting that it is the osa gene product that is
      active in suppression and that suppression does not require a protein-nucleic
      acid intermediate like that described for IncQ plasmids. Extracellular
      complementation experiments with tobacco leaf disks indicated that Osa blocks
      stable transfer of RSF1010 to plant cells by inhibiting transfer of VirE2, which
      is essential for the transfer of RSF1010 into plant cells, and not by inhibiting
      the actual transfer of RSF1010 itself. Our results suggest that Osa and RSF1010
      cause oncogenic suppression by using different mechanisms.

PMID- 15489438
TI  - ModA and ModB, two ADP-ribosyltransferases encoded by bacteriophage T4: catalytic
      properties and mutation analysis.
AB  - Bacteriophage T4 encodes three ADP-ribosyltransferases, Alt, ModA, and ModB.
      These enzymes participate in the regulation of the T4 replication cycle by ADP
      ribosylating a defined set of host proteins. In order to obtain a better
      understanding of the phage-host interactions and their consequences for
      regulating the T4 replication cycle, we studied cloning, overexpression, and
      characterization of purified ModA and ModB enzymes. Site-directed mutagenesis
      confirmed that amino acids, as deduced from secondary structure alignments, are
      indeed decisive for the activity of the enzymes, implying that the transfer
      reaction follows the Sn1-type reaction scheme proposed for this class of enzymes.
      In vitro transcription assays performed with Alt- and ModA-modified RNA
      polymerases demonstrated that the Alt-ribosylated polymerase enhances
      transcription from T4 early promoters on a T4 DNA template, whereas the
      transcriptional activity of ModA-modified polymerase, without the participation
      of T4-encoded auxiliary proteins for middle mode or late transcription, is
      reduced. The results presented here support the conclusion that ADP-ribosylation
      of RNA polymerase and of other host proteins allows initial phage-directed mRNA
      synthesis reactions to escape from host control. In contrast, subsequent
      modification of the other cellular target proteins limits transcription from
      phage early genes and participates in redirecting transcription to phage middle
      and late genes.

PMID- 15489439
TI  - The N-acetyl-D-glucosamine kinase of Escherichia coli and its role in murein
      recycling.
AB  - N-acetyl-D-glucosamine (GlcNAc) is a major component of bacterial cell wall
      murein and the lipopolysaccharide of the outer membrane. During growth, over 60%
      of the murein of the side wall is degraded, and the major products, GlcNAc
      anhydro-N-acetylmuramyl peptides, are efficiently imported into the cytoplasm and
      cleaved to release GlcNAc, anhydro-N-acetylmuramic acid, murein tripeptide (L-Ala
      D-Glu-meso-diaminopimelic acid), and D-alanine. Like murein tripeptide, GlcNAc is
      readily recycled, and this process was thought to involve phosphorylation, since
      GlcNAc-6-phosphate (GlcNAc-6-P) is efficiently used to synthesize murein or
      lipopolysaccharide or can be metabolized by glycolysis. Since the gene for GlcNAc
      kinase had not been identified, in this work we purified GlcNAc kinase (NagK)
      from Escherichia coli cell extracts and identified the gene by determining the N
      terminal sequence of the purified kinase. A nagK deletion mutant lacked
      phosphorylated GlcNAc in its cytoplasm, and the cell extract of the mutant did
      not phosphorylate GlcNAc, indicating that NagK is the only GlcNAc kinase
      expressed in E. coli. Unexpectedly, GlcNAc did not accumulate in a nagK nagEBACD
      mutant, though both GlcNAc and GlcNAc-6-P accumulate in the nagEBACD mutant,
      suggesting the existence of an alternative pathway (presumably repressed by
      GlcNAc-6-P) that reutilizes GlcNAc without the involvement of NagK.

PMID- 15489440
TI  - Construction of an Enterococcus faecalis Tn917-mediated-gene-disruption library
      offers insight into Tn917 insertion patterns.
AB  - Sequencing the insertion sites of 8,865 Tn917 insertions in Enterococcus faecalis
      strain OG1RF identified a hot spot in the replication terminus region
      corresponding to 6% of the genome where 65% of the transposons had inserted. In
      E. faecalis, Tn917 preferentially inserted at a 29-bp consensus sequence centered
      on TATAA, a 5-bp sequence that is duplicated during insertion. The regional
      insertion site preference at the chromosome terminus was not observed in another
      low-G+C gram-positive bacterium, Listeria monocytogenes, although the consensus
      insertion sequence was the same. The 8,865 Tn917 insertion sites sequenced in E.
      faecalis corresponded to only approximately 610 different open reading frames,
      far fewer than the predicted number of 2,400, assuming random insertion. There
      was no significant preference in orientation of the Tn917 insertions with either
      transcription or replication. Even though OG1RF has a smaller genome than strain
      V583 (2.8 Mb versus 3.2 Mb), the only E. faecalis strain whose sequence is in the
      public domain, over 10% of the Tn917 insertions appear to be in a OG1RF-specific
      sequence, suggesting that there are significant genomic differences among E.
      faecalis strains.

PMID- 15489441
TI  - Role of hha and ler in transcriptional regulation of the esp operon of
      enterohemorrhagic Escherichia coli O157:H7.
AB  - The locus of enterocyte effacement (LEE), which includes five major operons (LEE1
      through LEE4 and tir), enables enterohemorrhagic Escherichia coli (EHEC) O157:H7
      to produce attaching and effacing lesions on host cells. Expression of LEE2,
      LEE3, and tir is positively regulated by ler, a gene located in LEE1.
      Transcriptional regulation of the esp operon (LEE4), however, is not well
      defined. Transposon mutagenesis was used to identify transcriptional regulators
      of the esp operon by screening for mutants with increased beta-galactosidase
      activity in an EHEC O157:H7 strain harboring an esp::lac transcriptional fusion.
      All mutants with significant increases in beta-galactosidase activity had
      transposon insertions in hha (hha::Tn). Specific complementation of the hha::Tn
      mutation with a plasmid-encoded copy of hha reduced beta-galactosidase activity
      to the level expressed in the parental esp::lac strain. Purified Hha, however,
      bound poorly to the esp promoter, suggesting that Hha might repress the
      transcription of a positive regulator of esp. Transposon mutagenesis of a
      Deltahha esp::lac strain expressing elevated levels of beta-galactosidase
      resulted in ler mutants with reduced beta-galactosidase activity. Purified Hha
      bound to the ler promoter with a higher affinity, and complementation of a
      Deltahha mutation in a Deltahha ler::lac strain repressed beta-galactosidase
      activity to the level expressed in a ler::lac strain. A positive regulatory role
      of ler in esp expression was demonstrated by specific binding of Ler to the esp
      promoter, reduced expression of beta-galactosidase in Deltaler esp::lac strains
      with and without hha, and severalfold-increased transcription of ler and espA in
      strains lacking hha. These results indicate that hha-mediated repression of ler
      causes reduced expression of the esp operon.

PMID- 15489442
TI  - The BfeR regulator mediates enterobactin-inducible expression of Bordetella
      enterobactin utilization genes.
AB  - Utilization of the enterobactin siderophore by the respiratory pathogens
      Bordetella pertussis and Bordetella bronchiseptica is dependent on the BfeA outer
      membrane receptor. This study determined that production of BfeA was increased
      significantly in iron-starved bacteria upon supplementation of cultures with
      enterobactin. A 1.01-kb open reading frame, designated bfeR, encoding a predicted
      positive transcriptional regulator of the AraC family was identified upstream and
      divergently oriented from bfeA. In iron-depleted cultures containing
      enterobactin, a Bordetella bfeR mutant exhibited markedly decreased BfeA receptor
      production compared to that of the wild-type strain. Additionally, B. pertussis
      and B. bronchiseptica bfeR mutants exhibited impaired growth with ferric
      enterobactin as the sole source of iron, demonstrating that effective
      enterobactin utilization is bfeR dependent. Transcriptional analysis using bfeA
      lacZ reporter fusions in wild-type strains demonstrated that bfeA transcription
      was stimulated in iron-depleted conditions in the presence of enterobactin,
      compared to modest expression levels in cultures lacking enterobactin. In
      contrast, bfeA transcription in B. pertussis and B. bronchiseptica bfeR mutants
      was completely unresponsive to the enterobactin inducer. bfeA transcriptional
      analyses of a bfeA mutant demonstrated that induction by enterobactin did not
      require BfeA receptor-mediated uptake of the siderophore. These studies establish
      that bfeR encodes an enterobactin-dependent positive regulator of bfeA
      transcription in these Bordetella species.

PMID- 15489443
TI  - Characterization of nutrient-induced dispersion in Pseudomonas aeruginosa PAO1
      biofilm.
AB  - The processes associated with early events in biofilm formation have become a
      major research focus over the past several years. Events associated with
      dispersion of cells from late stage biofilms have, however, received little
      attention. We demonstrate here that dispersal of Pseudomonas aeruginosa PAO1 from
      biofilms is inducible by a sudden increase in carbon substrate availability. Most
      efficient at inducing dispersal were sudden increases in availability of
      succinate > glutamate > glucose that led to approximately 80% reductions in
      surface-associated biofilm biomass. Nutrient-induced biofilm dispersion was
      associated with increased expression of flagella (fliC) and correspondingly
      decreased expression of pilus (pilA) genes in dispersed cells. Changes in gene
      expression associated with dispersion of P. aeruginosa biofilms were studied by
      using DNA microarray technology. Results corroborated proteomic data that showed
      gene expression to be markedly different between biofilms and newly dispersed
      cells. Gene families that were upregulated in dispersed cells included those for
      flagellar and ribosomal proteins, kinases, and phage PF1. Within the biofilm,
      genes encoding a number of denitrification pathways and pilus biosynthesis were
      also upregulated. Interestingly, nutrient-induced dispersion was associated with
      an increase in the number of Ser/Thr-phosphorylated proteins within the newly
      dispersed cells, and inhibition of dephosphorylation reduced the extent of
      nutrient-induced dispersion. This study is the first to demonstrate that
      dispersal of P. aeruginosa from biofilms can be induced by the addition of simple
      carbon sources. This study is also the first to demonstrate that dispersal of P.
      aeruginosa correlates with a specific dispersal phenotype.

PMID- 15489444
TI  - A nonribosomal peptide synthetase with a novel domain organization is essential
      for siderophore biosynthesis in Vibrio anguillarum.
AB  - Anguibactin, a siderophore produced by Vibrio anguillarum, is synthesized via a
      nonribosomal peptide synthetase (NRPS) mechanism. We have identified a gene from
      the V. anguillarum plasmid pJM1 that encodes a 78-kDa NRPS protein termed AngM,
      which is essential in the biosynthesis of anguibactin. The predicted AngM amino
      acid sequence shows regions of homology to the consensus sequence for the
      peptidyl carrier protein (PCP) and the condensation (C) domains of NRPSs, and
      curiously, these two domains are not associated with an adenylation (A) domain.
      Substitution by alanine of the serine 215 in the PCP domain and of histidine 406
      in the C domain of AngM results in an anguibactin-deficient phenotype,
      underscoring the importance of these two domains in the function of this protein.
      The mutations in angM that affected anguibactin production also resulted in a
      dramatic attenuation of the virulence of V. anguillarum 775, highlighting the
      importance of this gene in the establishment of a septicemic infection in the
      vertebrate host. Transcription of the angM gene is initiated at an upstream
      transposase gene promoter that is repressed by the Fur protein in the presence of
      iron. Analysis of the sequence at this promoter showed that it overlaps the iron
      transport-biosynthesis promoter and operates in the opposite direction.

PMID- 15489445
TI  - The NtcA-dependent P1 promoter is utilized for glnA expression in N2-fixing
      heterocysts of Anabaena sp. strain PCC 7120.
AB  - Expression of the glnA gene encoding glutamine synthetase, a key enzyme in
      nitrogen metabolism, is subject to a variety of regulatory mechanisms in
      different organisms. In the filamentous, N(2)-fixing cyanobacterium Anabaena sp.
      strain PCC 7120, glnA is expressed from multiple promoters that generate several
      transcripts whose abundance is influenced by NtcA, the transcription factor
      exerting global nitrogen control in cyanobacteria. Whereas RNA(I) originates from
      a canonical NtcA-dependent promoter (P(1)) and RNA(II) originates from a
      sigma(70)-type promoter (P(2)), RNA(IV) is influenced by NtcA but the
      corresponding promoter (P(3)) does not have the structure of NtcA-activated
      promoters. Using RNA isolated from Anabaena filaments grown under different
      nitrogen regimens, we observed, in addition to these transcripts, RNA(V), which
      has previously been detected only in in vitro transcription assays and should
      originate from P(4). However, in heterocysts, which are differentiated cells
      specialized in N(2) fixation, RNA(I) was the almost exclusive glnA transcript.
      Analysis of P(glnA)::lacZ fusions containing different fragments of the glnA
      upstream region confirmed that fragments carrying P(1), P(2), or P(3) and P(4)
      have the ability to promote transcription. Mutation of the NtcA-binding site in
      P(1) eliminated P(1)-directed transcription and allowed increased use of P(2).
      The NtcA-binding site in the P(1) promoter and binding of NtcA to this site
      appear to be key factors in determining glnA gene expression in vegetative cells
      and heterocysts.

PMID- 15489446
TI  - Temporal analysis of Coxiella burnetii morphological differentiation.
AB  - Coxiella burnetii undergoes a poorly defined developmental cycle that generates
      morphologically distinct small-cell variants (SCV) and large-cell variants (LCV).
      We developed a model to study C. burnetii morphogenesis that uses Vero cells
      synchronously infected with homogeneous SCV (Nine Mile strain in phase II)
      harvested from aged infected cell cultures. A time course transmission electron
      microscopic analysis over 8 days of intracellular growth was evaluated in
      conjunction with one-step growth curves to correlate morphological
      differentiations with growth cycle phase. Lag phase occurred during the first 2
      days postinfection (p.i.) and was primarily composed of SCV-to-LCV morphogenesis.
      LCV forms predominated over the next 4 days, during which exponential growth was
      observed. Calculated generation times during exponential phase were 10.2 h (by
      quantitative PCR assay) and 11.7 h (by replating fluorescent focus-forming unit
      assay). Stationary phase began at approximately 6 days p.i. and coincided with
      the reappearance of SCV, which increased in number at 8 days p.i. Quantitative
      reverse transcriptase-PCR demonstrated maximal expression of scvA, which encodes
      an SCV-specific protein, at 8 days p.i., while immunogold transmission electron
      microscopy revealed degradation of ScvA throughout lag and exponential phases,
      with increased expression observed at the onset of stationary phase.
      Collectively, these results indicate that the overall growth cycle of C. burnetii
      is characteristic of a closed bacterial system and that the replicative form of
      the organism is the LCV. The experimental model described in this report will
      allow a global transcriptome and proteome analysis of C. burnetii developmental
      forms.

PMID- 15489447
TI  - TouR-mediated effector-independent growth phase-dependent activation of the
      sigma54 Ptou promoter of Pseudomonas stutzeri OX1.
AB  - Transcription of the catabolic touABCDEF operon, encoding the toluene-o-xylene
      monooxygenase of Pseudomonas stutzeri OX1, is driven by the sigma(54)-dependent
      Ptou promoter, whose activity is controlled by the phenol-responsive NtrC-like
      activator TouR. In this paper we describe for the first time a peculiar
      characteristic of this system, namely, that Ptou transcription is activated in a
      growth phase-dependent manner in the absence of genuine effectors of the cognate
      TouR regulator. This phenomenon, which we named gratuitous activation, was
      observed in the native strain P. stutzeri OX1, as well as in a Pseudomonas putida
      PaW340 host harboring the reconstructed tou regulatory circuit. Regulator
      promoter swapping experiments demonstrated that the presence of TouR is necessary
      and sufficient for imposing gratuitous activation on the Ptou promoter, as well
      as on other sigma(54)-dependent catabolic promoters, whereas the highly similar
      phenol-responsive activator DmpR is unable to activate the Ptou promoter in the
      absence of effectors. We show that this phenomenon is specifically triggered by
      carbon source exhaustion but not by nitrogen starvation. An updated model of the
      tou regulatory circuit is presented.

PMID- 15489448
TI  - Diversion of the metabolic flux from pyruvate dehydrogenase to pyruvate oxidase
      decreases oxidative stress during glucose metabolism in nongrowing Escherichia
      coli cells incubated under aerobic, phosphate starvation conditions.
AB  - Ongoing aerobic metabolism in nongrowing cells may generate oxidative stress. It
      is shown here that the levels of thiobarbituric acid-reactive substances
      (TBARSs), which measure fragmentation products of oxidized molecules, increased
      strongly at the onset of starvation for phosphate (P(i)). This increase in TBARS
      levels required the activity of the histone-like nucleoid-structuring (H-NS)
      protein. TBARS levels weakly increased further in DeltaahpCF mutants deficient in
      alkyl hydroperoxide reductase (AHP) activity during prolonged metabolism of
      glucose to acetate. Inactivation of pyruvate oxidase (PoxB) activity decreased
      the production of acetate by half and significantly increased the production of
      TBARS. Overall, these data suggest that during incubation under aerobic, P(i)
      starvation conditions, metabolic flux is diverted from the pyruvate dehydrogenase
      (PDH) complex (NAD dependent) to PoxB (NAD independent). This shift may decrease
      the production of NADH and in turn the adventitious production of H(2)O(2) by
      NADH dehydrogenase in the respiratory chain. The residual low levels of H(2)O(2)
      produced during prolonged incubation can be scavenged efficiently by AHP.
      However, high levels of H(2)O(2) may be reached transiently at the onset of
      stationary phase, primarily because H-NS may delay the metabolic shift from PDH
      to PoxB.

PMID- 15489449
TI  - AlgX is a periplasmic protein required for alginate biosynthesis in Pseudomonas
      aeruginosa.
AB  - Alginate, an exopolysaccharide produced by Pseudomonas aeruginosa, provides the
      bacterium with a selective advantage that makes it difficult to eradicate from
      the lungs of cystic fibrosis (CF) patients. Previous studies identified a gene,
      algX, within the alginate biosynthetic gene cluster on the P. aeruginosa
      chromosome. By probing cell fractions with anti-AlgX antibodies in a Western
      blot, AlgX was localized within the periplasm. Consistent with these results is
      the presence of a 26-amino-acid signal sequence. To examine the requirement for
      AlgX in alginate biosynthesis, part of algX in P. aeruginosa strain FRD1::pJLS3
      was replaced with a nonpolar gentamicin resistance cassette. The resulting
      algXDelta::Gm mutant was verified by PCR and Western blot analysis and was
      phenotypically nonmucoid (non-alginate producing). The algXDelta::Gm mutant was
      restored to the mucoid phenotype with wild-type P. aeruginosa algX provided on a
      plasmid. The algXDelta::Gm mutant was found to secrete dialyzable oligouronic
      acids of various lengths. Mass spectroscopy and Dionex chromatography indicated
      that the dialyzable uronic acids are mainly mannuronic acid dimers resulting from
      alginate lyase (AlgL) degradation of polymannuronic acid. These studies suggest
      that AlgX is part of a protein scaffold that surrounds and protects newly formed
      polymers from AlgL degradation as they are transported within the periplasm for
      further modification and eventual transport out of the cell.

PMID- 15489450
TI  - Characterization of EvgAS-YdeO-GadE branched regulatory circuit governing
      glutamate-dependent acid resistance in Escherichia coli.
AB  - Escherichia coli prefers growth in neutral pH environments but can withstand
      extremely acidic conditions (pH 2) for long periods. Of the four E. coli systems
      that contribute to acid resistance, one, the glutamate-dependent system, is
      remarkable in its efficacy and regulatory complexity. The resistance mechanism
      involves the intracellular consumption of protons by the glutamate decarboxylase
      isozymes GadA and GadB. The antiporter GadC then exports the product, gamma
      aminobutyric acid, in exchange for fresh glutamate. A microarray study using
      overexpressed regulators uncovered evgAS and ydeO as potential regulators of
      gadE, now known to encode the essential activator of the gadA and gadBC genes.
      Examination of evgA and ydeO under normal expression conditions revealed that
      their products do activate gadE expression but only under specific conditions.
      They were important during exponential growth in acidified minimal medium
      containing glucose but were unnecessary for gadE expression in stationary-phase
      cells grown in complex medium. The response regulator EvgA activates gadE
      directly and indirectly via induction of the AraC-like regulator ydeO. Evidence
      obtained using gadE-lacZ operon fusions also revealed that GadE was autoinduced.
      Electrophoretic mobility shift assays indicated that EvgA, YdeO, and GadE bind to
      different regions upstream of gadE, indicating they all act directly at the gadE
      promoter. Since GadE controls the expression of numerous genes besides gadA and
      gadBC, the relevance of these regulatory circuits extends beyond acid resistance.

PMID- 15489451
TI  - Analysis of promoter elements involved in the transcriptional initiation of RpoS
      dependent Borrelia burgdorferi genes.
AB  - Borrelia burgdorferi, the causative agent of Lyme disease, encodes an RpoS
      ortholog (RpoS(Bb)) that controls the temperature-inducible differential
      expression of at least some of the spirochete's lipoprotein genes, including ospC
      and dbpBA. To begin to dissect the determinants of RpoS(Bb) recognition of, and
      selectivity for, its dependent promoters, we linked a green fluorescent protein
      reporter to the promoter regions of several B. burgdorferi genes with well
      characterized expression patterns. Consistent with the expression patterns of the
      native genes/proteins in B. burgdorferi strain 297, we found that expression of
      the ospC, dbpBA, and ospF reporters in the spirochete was RpoS(Bb) dependent,
      while the ospE and flaB reporters were RpoS(Bb) independent. To compare promoter
      recognition by RpoS(Bb) with that of the prototype RpoS (RpoS(Ec)), we also
      introduced our panel of constructs into Escherichia coli. In this surrogate,
      maximal expression from the ospC, dbpBA, and ospF promoters clearly required
      RpoS, although in the absence of RpoS(Ec) the ospF promoter was weakly recognized
      by another E. coli sigma factor. Furthermore, RpoS(Bb) under the control of an
      inducible promoter was able to complement an E. coli rpoS mutant, although
      RpoS(Ec) and RpoS(Bb) each initiated greater activity from their own dependent
      promoters than they did from those of the heterologous sigma factor. Genetic
      analysis of the ospC promoter demonstrated that (i) the T(-14) in the presumptive
      -10 region plays an important role in sigma factor recognition in both organisms
      but is not as critical for transcriptional initiation by RpoS(Bb) as it is for
      RpoS(Ec); (ii) the nucleotide at the -15 position determines RpoS or sigma(70)
      selectivity in E. coli but does not serve the same function in B. burgdorferi;
      and (iii) the 110-bp region upstream of the core promoter is not required for
      RpoS(Ec)- or RpoS(Bb)-dependent activity in E. coli but is required for maximal
      expression from this promoter in B. burgdorferi. Taken together, the results of
      our studies suggest that the B. burgdorferi and E. coli RpoS proteins are able to
      catalyze transcription from RpoS-dependent promoters of either organism, but at
      least some of the nucleotide elements involved in transcriptional initiation and
      sigma factor selection in B. burgdorferi play a different role than has been
      described for E. coli.

PMID- 15489452
TI  - RpoS proteolysis is regulated by a mechanism that does not require the SprE
      (RssB) response regulator phosphorylation site.
AB  - In Escherichia coli the response regulator SprE (RssB) facilitates degradation of
      the sigma factor RpoS by delivering it to the ClpXP protease. This process is
      regulated: RpoS is degraded in logarithmic phase but becomes stable upon carbon
      starvation, resulting in its accumulation. Because SprE contains a CheY domain
      with a conserved phosphorylation site (D58), the prevailing model posits that
      this control is mediated by phosphorylation. To test this model, we mutated the
      conserved response regulator phosphorylation site (D58A) of the chromosomal
      allele of sprE and monitored RpoS levels in response to carbon starvation. Though
      phosphorylation contributed to the SprE basal activity, we found that RpoS
      proteolysis was still regulated upon carbon starvation. Furthermore, our results
      indicate that phosphorylation of wild-type SprE occurs by a mechanism that is
      independent of acetyl phosphate.

PMID- 15489453
TI  - Use of in vivo expression technology to identify genes important in growth and
      survival of Pseudomonas fluorescens Pf0-1 in soil: discovery of expressed
      sequences with novel genetic organization.
AB  - Studies were undertaken to determine the genetic needs for the survival of
      Pseudomonas fluorescens Pf0-1, a gram-negative soil bacterium potentially
      important for biocontrol and bioremediation, in soil. In vivo expression
      technology (IVET) identified 22 genes with elevated expression in soil relative
      to laboratory media. Soil-induced sequences included genes with probable
      functions of nutrient acquisition and use, and of gene regulation. Ten sequences,
      lacking similarity to known genes, overlapped divergent known genes, revealing a
      novel genetic organization at those soil-induced loci. Mutations in three soil
      induced genes led to impaired early growth in soil but had no impact on growth in
      laboratory media. Thus, IVET studies have identified sequences important for soil
      growth and have revealed a gene organization that was undetected by traditional
      laboratory approaches.

PMID- 15489454
TI  - AplA, a member of a new class of phycobiliproteins lacking a traditional role in
      photosynthetic light harvesting.
AB  - All known phycobiliproteins have light-harvesting roles during photosynthesis and
      are found in water-soluble phycobilisomes, the light-harvesting complexes of
      cyanobacteria, cyanelles, and red algae. Phycobiliproteins are chromophore
      bearing proteins that exist as heterodimers of alpha and beta subunits, possess a
      number of highly conserved amino acid residues important for dimerization and
      chromophore binding, and are invariably 160 to 180 amino acids long. A new and
      unusual group of proteins that is most closely related to the allophycocyanin
      members of the phycobiliprotein superfamily has been identified. Each of these
      proteins, which have been named allophycocyanin-like (Apl) proteins, apparently
      contains a 28-amino-acid extension at its amino terminus relative to
      allophycocyanins. Apl family members possess the residues critical for
      chromophore interactions, but substitutions are present at positions implicated
      in maintaining the proper alpha-beta subunit interactions and tertiary structure
      of phycobiliproteins, suggesting that Apl proteins are able to bind chromophores
      but fail to adopt typical allophycocyanin conformations. AplA isolated from the
      cyanobacterium Fremyella diplosiphon contained a covalently attached chromophore
      and, although present in the cell under a number of conditions, was not detected
      in phycobilisomes. Thus, Apl proteins are a new class of photoreceptors with a
      different cellular location and structure than any previously described members
      of the phycobiliprotein superfamily.

PMID- 15489455
TI  - Biosynthesis of cryptic lipopolysaccharide glycoforms in Haemophilus influenzae
      involves a mechanism similar to that required for O-antigen synthesis.
AB  - It is generally thought that mucosal bacterial pathogens of the genera
      Haemophilus, Neisseria, and Moraxella elaborate lipopolysaccharide (LPS) that is
      fundamentally different from that of enteric organisms that express O-specific
      polysaccharide side chains. Haemophilus influenzae elaborates short-chain LPS
      that has a role in the pathogenesis of H. influenzae infections. We show that the
      synthesis of LPS in this organism can no longer be as clearly distinguished from
      that in other gram-negative bacteria that express an O antigen. We provide
      evidence that a region of the H. influenzae genome, the hmg locus, is involved in
      the synthesis of glycoforms in which tetrasaccharide units are added en bloc, not
      stepwise, to the normal core glycoforms, similar to the biosynthesis of an O
      antigen.

PMID- 15489456
TI  - Interactions between the PAS and HAMP domains of the Escherichia coli aerotaxis
      receptor Aer.
AB  - The Escherichia coli energy-sensing Aer protein initiates aerotaxis towards
      environments supporting optimal cellular energy. The Aer sensor is an N-terminal,
      FAD-binding, PAS domain. The PAS domain is linked by an F1 region to a membrane
      anchor, and in the C-terminal half of Aer, a HAMP domain links the membrane
      anchor to the signaling domain. The F1 region, membrane anchor, and HAMP domain
      are required for FAD binding. Presumably, alterations in the redox potential of
      FAD induce conformational changes in the PAS domain that are transmitted to the
      HAMP and C-terminal signaling domains. In this study we used random mutagenesis
      and intragenic pseudoreversion analysis to examine functional interactions
      between the HAMP domain and the N-terminal half of Aer. Missense mutations in the
      HAMP domain clustered in the AS-2 alpha-helix and abolished FAD binding to Aer,
      as previously reported. Three amino acid replacements in the Aer-PAS domain,
      S28G, A65V, and A99V, restored FAD binding and aerotaxis to the HAMP mutants.
      These suppressors are predicted to surround a cleft in the PAS domain that may
      bind FAD. On the other hand, suppression of an Aer-C253R HAMP mutant was specific
      to an N34D substitution with a predicted location on the PAS surface, suggesting
      that residues C253 and N34 interact or are in close proximity. No suppressor
      mutations were identified in the F1 region or membrane anchor. We propose that
      functional interactions between the PAS domain and the HAMP AS-2 helix are
      required for FAD binding and aerotactic signaling by Aer.

PMID- 15489457
TI  - Increased stability of bmr3 mRNA results in a multidrug-resistant phenotype in
      Bacillus subtilis.
AB  - A spontaneous mutant isolated in the presence of a high concentration of
      puromycin acquired a multidrug-resistant phenotype. Expression of the bmr3 gene
      was dramatically increased. A base substitution, T to A at the +4 position,
      detected in the mutant resulted in the stabilization of bmr3 mRNA.

PMID- 15489458
TI  - The Aer protein of Escherichia coli forms a homodimer independent of the
      signaling domain and flavin adenine dinucleotide binding.
AB  - In vivo cross-linking between native cysteines in the Aer receptor of Escherichia
      coli showed dimer formation at the membrane anchor and in the putative HAMP
      domain. Dimers also formed in mutants that did not bind flavin adenine
      dinucleotide and in truncated peptides without a signaling domain and part of the
      HAMP domain.

PMID- 15489459
TI  - Molecular basis of the indole-negative reaction in Shigella strains: extensive
      damages to the tna operon by insertion sequences.
AB  - The molecular basis of the loss of tryptophan utilization (indole-negative
      phenotype) of Shigella strains, in effect clones of Escherichia coli, was
      investigated. Analysis of the tna operon of 23 Shigella strains representing each
      of the indole-negative serotypes revealed that insertion sequence-mediated
      insertion and/or deletions damaged the tna operon, leading to inability to
      convert tryptophan to indole. These events differ for cluster 1, cluster 3, and
      the outlier Shigella strains, confirming our previous observation of independent
      origins of these lineages from within E. coli. Parallel loss of the trait and
      prevalence of indole-negative strains suggest that the trait is deleterious in
      Shigella strains and advantages those without it.

PMID- 15489460
TI  - AMASS: software for automatically validating the quality of MS/MS spectrum from
      SEQUEST results.
AB  - Time-consuming and experience-dependent manual validations of tandem mass spectra
      are usually applied to SEQUEST results. This inefficient method has become a
      significant bottleneck for MS/MS data processing. Here we introduce a program
      AMASS (advanced mass spectrum screener), which can filter the tandem mass spectra
      of SEQUEST results by measuring the match percentage of high-abundant ions and
      the continuity of matched fragment ions in b, y series. Compared with Xcorr and
      DeltaCn filter, AMASS can increase the number of positives and reduce the number
      of negatives in 22 datasets generated from 18 known protein mixtures. It
      effectively removed most noisy spectra, false interpretations, and about half of
      poor fragmentation spectra, and AMASS can work synergistically with Rscore
      filter. We believe the use of AMASS and Rscore can result in a more accurate
      identification of peptide MS/MS spectra and reduce the time and energy for manual
      validation.

PMID- 15489462
TI  - Correlates of obesity in African-American girls: an overview.

PMID- 15489463
TI  - Parental cultural perspectives in relation to weight-related behaviors and
      concerns of African-American girls.
AB  - OBJECTIVE: To determine whether cultural perspectives of parents may influence
      children's eating and physical activity behaviors and patterns of weight gain.
      RESEARCH METHODS AND PROCEDURES: African-American girls (ages 8 to 10 years) and
      their parents (or caregivers) (n = 210) participated at one of four Girls Health
      Enrichment Multisite Studies Phase 1 Field Centers. At baseline, parents
      completed questionnaires adapted from the African-American Acculturation Scale
      (AAAS), the Multiethnic Identity Scale (MEIS), and an original question on Global
      Cultural Identity. Girls' baseline measures included physical activity assessment
      by accelerometer, 24-hour dietary recalls, and questionnaires about body image
      and weight concerns. RESULTS: Principal components analysis indicated the
      expected AAAS and MEIS factor structures, with moderate to good internal
      consistency (Cronbach's alpha = 0.61 to 0.82) and some intercorrelation among
      these measures (r = 0.17 to 0.57). Overall mean (SD) AAAS subscale scores of 4.1
      (2.1) and 5.5 (1.8) of a possible 7 and 3.0 (0.9) of a possible 4 on the MEIS
      indicated, respectively, moderate to high levels of parental African-American
      cultural orientation and identity with moderate variability. Parental AAAS and
      MEIS scores were inversely correlated with girls' body image discrepancy and
      weight concern. One AAAS subscale was positively associated with total energy
      intake and percentage energy from fat. Overall, however, parental AAAS and MEIS
      scores were unrelated or inconsistently related to girls' physical activity and
      diet measures. DISCUSSION: The AAAS and MEIS measures had acceptable psychometric
      properties, except for weight concern, but did not give a consistent picture of
      how parental perspectives related to the girls' baseline attitudes and behaviors.

PMID- 15489464
TI  - Anthropometric, parental, and psychosocial correlates of dietary intake of
      African-American girls.
AB  - OBJECTIVE: This paper identifies the anthropometric, parental, and psychosocial
      characteristics and meal practices (e.g., breakfast skipping and number of meals
      and snacks consumed) associated with consumption of total energy, percent energy
      from fat, fruit, 100% fruit juice, vegetables, sweetened beverages, and water
      among 8- to 10-year-old African-American girls. RESEARCH METHODS AND PROCEDURES:
      This study included 114 8- to 10-year-old African-American girls and a parent or
      primary caregiver. Girls and a parent or primary caregiver completed several
      dietary questionnaires. Two 24-hour dietary recalls were conducted with each
      girl. Height and weight were measured. Separate hierarchical regression analyses
      were conducted for each dependent dietary variable; potential field center
      differences were examined. RESULTS: The number of meals and snacks consumed was
      correlated with energy intake. Lower BMI was related to higher vegetable
      consumption, and the number of snacks consumed was positively related to
      sweetened beverage consumption. Greater low-fat food preparation practices
      reported by parents were related to lower consumption of fat as a percentage of
      total energy. DISCUSSION: Dietary behavior differed across geographic areas. Low
      fat food preparation practices in the home seemed to be an important influence on
      the percentage of energy consumed from fat. Greater vegetable consumption was
      associated with lower BMI. Interventions to prevent excessive weight gain in
      African-American girls should encourage low-fat food preparation in the home and
      greater consumption of vegetables.

PMID- 15489465
TI  - African-American girls' dietary intake while watching television.
AB  - OBJECTIVE: Television viewing has been associated with childhood obesity,
      although the mechanisms that link television viewing to higher BMI have not been
      established. Therefore, our objectives, in this report, were to describe the
      amount and types of foods that African-American girls consume while watching
      television and to examine the associations between African-American girls' BMI
      and the food they consume while watching television. RESEARCH METHODS AND
      PROCEDURES: Data were collected from 210 8- to 10-year-old African-American girls
      at four field centers by trained and certified nutritionists. Two nonconsecutive
      24-hour dietary recalls were collected from each girl. For each eating episode
      reported, the girls were asked if they had been watching television while eating.
      Height and weight were collected using standard methods and used to calculate
      BMI. RESULTS: The data were analyzed separately by field center. The proportion
      of average daily energy intake that the girls consumed while watching television
      ranged from 26.9% to 35.0%. At all field centers, 40% to 50% of evening meals
      were consumed while watching television. None of the Spearman correlations
      between girls' BMI and the amount and type of foods consumed while watching
      television or at other times during the day were statistically significant (p >
      0.05). DISCUSSION: This research revealed that a significant proportion of
      African-American girls' daily energy intake is consumed while watching
      television. Interventions that target reductions in food consumption while
      watching television or reducing television viewing may be effective strategies to
      decrease children's energy intakes. These results support a need for research to
      test the efficacy of these approaches.

PMID- 15489466
TI  - Physical activity among African-American girls: the role of parents and the home
      environment.
AB  - OBJECTIVES: African-American girls are at increased risk for becoming overweight.
      Increased physical activity may prevent this. This study examines measurements of
      girls' physical activity and associations with: BMI, parent's reported self
      efficacy and support for helping daughters be active, girl's perceived support
      from parents for physical activity, parent's and girl's perceived neighborhood
      safety and access to facilities, and family environment. RESEARCH METHODS AND
      PROCEDURES: Fifty-two 8- to 10-year-old African-American girls and their primary
      caregiver in the Minneapolis/St. Paul area participated in the Girls Health
      Enrichment Multisite Studies pilot intervention to prevent weight gain by
      promoting healthy eating and physical activity. Data collected included height,
      weight, physical activity level, and physical activity-related psychosocial
      measures from girl and parent. Girls wore an activity monitor for 3 days to
      assess activity level. Correlations were computed among the average minutes per
      day of moderate to vigorous activity between 12 pm and 6 pm and BMI and
      psychosocial measures. RESULTS: BMI was inversely correlated with moderate to
      vigorous activity (r = -0.35, p < 0.01), whereas parent's self-efficacy for
      supporting daughter to be active was positively correlated with activity (r =
      0.45, p < 0.001). There was a trend for parent's reported support of daughter's
      activity level to be associated with activity (r = 0.26, p < 0.06). Girl's
      perception of parent's support for physical activity, perceived neighborhood
      safety and access to facilities, and family environment were not associated with
      girl's activity levels. DISCUSSION: Interventions to increase physical activity
      among preadolescent African-American girls may benefit from a parental component
      to encourage support and self-efficacy for daughters' physical activity.

PMID- 15489467
TI  - Covariability in diet and physical activity in African-American girls.
AB  - OBJECTIVE: Our goal was to examine 12-week covariability in diet and physical
      activity changes among 8- to 10-year-old African-American girls and if these
      changes predicted percent change in BMI. RESEARCH METHODS AND PROCEDURES:
      Covariability among percent changes [(post - pre)/pre x 100] in nutrients, food
      groups, and physical activity was assessed among 127 8- to 10-year-old African
      American girls. Pearson correlation and hierarchical linear regression analyses
      were performed. RESULTS: Percent change in percentage kilocalories from
      carbohydrate was negatively correlated with percent change in both percentage
      kilocalories from fat (r = -0.85; p < or = 0.01) and protein (r = -0.51; p < or =
      0.01). No statistically significant relationships were observed in percent
      changes among food group variables. Negative relationships were observed between
      percent changes in fruit/100% juice and percentage kilocalories from fat (r = 
      0.20; p < or = 0.05) and between percent changes in minutes of moderate-to
      vigorous and sedentary activity (r = -0.60; p < or = 0.01). No significant
      associations were observed between percent change in moderate-to-vigorous
      physical activity and diet variables or percent change in BMI or waist
      circumference and percent change in diet or physical activity. DISCUSSION: No
      relationships were observed between percent changes in physical activity and
      dietary variables. Percent change in diet and/or physical activity did not
      predict percent change in BMI. This may have been due to the small sample size,
      the small changes in diet or physical activity, the short duration of the
      intervention, or because data from different interventions were combined.
      Understanding these relationships could have significant implications for
      addressing the obesity epidemic.

PMID- 15489468
TI  - Relationship between physical activity and diet among African-American girls.
AB  - OBJECTIVE: To examine the cross-sectional relationships between physical activity
      and dietary behaviors among 8- to 10-year-old African-American girls. RESEARCH
      METHODS AND PROCEDURES: Two hundred ten 8- to 10-year-old African-American girls
      from four field centers participated. Computer Science and Applications (CSA)
      activity monitors were worn for 3 days. CSA data were expressed as mean CSA
      counts per minute, mean minutes of moderate to vigorous activity per day, and
      mean metabolic equivalents (METS) per minute. Two nonconsecutive 24-hour dietary
      recalls were analyzed for kilocalories; percent kilocalories from fat; daily
      servings of fruit, 100% fruit juice, and vegetables; sweetened beverages; and
      water consumption. Height and weight were measured, and information on household
      income, material possessions, and participant age were obtained. RESULTS: All
      three expressions of physical activity were significantly negatively associated
      with percentage calories from fat (r = -0.147 to -0.177, p < 0.01), and mean METS
      per minute were significantly positively associated with percentage calories from
      carbohydrate (r = 0.149, p < 0.05) after controlling for household income,
      material possessions, field center, and total caloric intake. Income was
      inversely associated with percentage calories from fat. DISCUSSION: Physical
      activity and dietary fat consumption were inversely related among African
      American girls. Efforts to prevent obesity in preadolescent African-American
      girls should focus on increasing physical activity and lowering dietary fat
      consumption.

PMID- 15489469
TI  - Early sexual maturation, body composition, and obesity in African-American girls.
AB  - OBJECTIVE: To describe associations between sexual maturation and body
      composition in a sample of African-American girls who were participants in phase
      1 pilot interventions of the Girls Health Enrichment Multisite Studies. RESEARCH
      METHODS AND PROCEDURES: Stature, weight, and waist circumference were measured.
      Pubic hair and breast development were assessed, and body composition was
      measured by DXA for 147 African-American girls who were 8 to 10 years of age from
      three field centers. Participants had BMI > or =25th percentile for age (one
      site) or BMI > or =50th percentile for age. RESULTS: Girls Health Enrichment
      Multisite Studies girls had greater BMI, fat mass, and percentage body fat than
      national norms and relatively earlier initiation of breast development and pubic
      hair. Increasing stages of breast development, but not stages of pubic hair, were
      related to increased stature, waist circumference, BMI, lean mass, fat mass, and
      percentage of body fat. Pubescent girls (breast stage > or = 2) were greater than
      six times as likely to be classified as at risk of overweight (BMI > or = 85th
      percentile) and greater than eight times as likely to be classified as overweight
      (BMI > or = 95th percentile) as prepubescent counterparts. Adjusted odds ratios
      for advanced breast development [breast stage > or = 2 (8 years) or > or = 3 (9
      and 10 years)] were 3.6 for risk of overweight and for overweight compared to
      girls with average or less than average breast development. DISCUSSION: Sexual
      maturation is important to consider in understanding the classification of
      overweight and the development of obesity during adolescence. Breast development
      and pubic hair development should be considered separately for their associations
      with growth and body composition.

PMID- 15489470
TI  - Assessing weight-related biochemical cardiovascular risk factors in African
      American girls.
AB  - OBJECTIVE: Hyperinsulinemia/insulin resistance is a risk factor for future type 2
      diabetes. Fasting insulin and blood lipids serve as direct indicators of
      subsequent risk and as biochemical markers of metabolically significant
      adiposity. We examined the feasibility of obtaining fasting blood samples and
      report correlates of these biochemical markers in an understudied population
      sample. RESEARCH METHODS AND PROCEDURES: Fasting samples were requested from
      African-American girls, 8.00 to 10.99 years of age, for insulin, glucose, and
      lipid concentrations. Indices of insulin sensitivity and secretion were
      calculated and correlated with anthropometric, dietary, physical activity, and
      body composition data. RESULTS: Samples were obtained from 119 of 210 (57%)
      girls, varying from 5% to 86% across the four field centers. Glucose ranged from
      71 to 104 mg/dL. Eleven percent had insulin concentrations >20 mU/liter. One girl
      had a triglyceride concentration >130 mg/dL. Thirteen percent had total
      cholesterol >200 mg/dL, whereas all subjects had high-density lipoprotein (HDL)
      cholesterol of > or =35 mg/dL. Fourteen percent had low-density lipoprotein
      levels >130 mg/dL. Insulin concentrations showed consistently strong associations
      with measures of body weight (rs = 0.54 to 0.67); glucose, HDL, and LDL showed
      weaker correlations (rs = -0.11 to 0.22). Insulin concentration was highly
      correlated with indices of both insulin secretion and resistance (rs = 0.99).
      DISCUSSION: Fasting blood samples in young African-American girls were obtained
      with reasonable cooperation in three of the four field centers involved in this
      community-based study. Fasting insulin, glucose, LDL, and HDL concentrations may
      help evaluate future diabetes and cardiovascular risk in children of this age.

PMID- 15489471
TI  - Is it time to call time on the scleral buckle?

PMID- 15489472
TI  - Orbital steroid injections.

PMID- 15489473
TI  - Visual and ocular findings in children adopted from eastern Europe.
AB  - AIMS: To evaluate ophthalmological findings in children adopted from eastern
      Europe. METHODS: A prospective study on 72/99 children, born 1990-5 and adopted
      from eastern Europe to western Sweden during 1993-7 was performed. The children
      (41 boys; mean age 7.5 years) were compared with an age and sex matched reference
      group ("ref") of Swedish children. RESULTS: 78% of the adopted children had
      abnormal ocular findings. 26% (ref 4%) had visual acuity (VA) of the better eye <
      or = 0.5 (> or = 0.3 logMAR) (p = 0.0001) and 8% (ref 0%) were visually impaired
      (p = 0.01). Amblyopia was found in 15% (ref 2%) (p = 0.005). 22% (ref 10%) were
      hyperopic (> or = 2.0 D SE) (NS) and 10% (ref 1%) were myopic (> or = 0.5 D SE)
      (p = 0.03). Astigmatism (> or = 0.75 D) was found in 51% (ref 23%) (p = 0.004).
      32% (ref 2%) had strabismus (p<0.0001), mostly esotropia. Four cases had
      bilateral optic nerve hypoplasia, in three of whom a history of suspected
      prenatal alcohol exposure was documented. One child had congenital glaucoma.
      Signs of visuoperceptual problems were recorded in 37% (ref 1%) (p<0.0001).
      CONCLUSION: In this study, children adopted from eastern Europe had a high
      frequency of ophthalmological findings. Consequently, it is strongly recommended
      that an ophthalmological examination be performed in these children after arrival
      in their new home country.

PMID- 15489474
TI  - Gender equity and trichiasis surgery in the Vietnam and Tanzania national
      trachoma control programmes.
AB  - AIMS: To calculate the gender distribution of trichiasis cases in trachoma
      communities in Vietnam and Tanzania, and the gender distribution of surgical
      cases, to determine if women are using surgical services proportional to their
      needs. METHODS: Population based data from surveys done in Tanzania and Vietnam
      as part of the national trachoma control programmes were used to determine the
      rate of trichiasis by gender in the population. Surgical records provided data on
      the gender ratio of surgical cases. RESULTS: The rates of trichiasis in both
      countries are from 1.4-fold to sixfold higher in females compared to males. In
      both countries, the female to male rate of surgery was the same or even higher
      than the female to male rate of trichiasis in the population. CONCLUSIONS: These
      data provide assurance of gender equity in the provision and use of trichiasis
      surgery services in the national programmes of these two countries. Such simple
      analyses should be used by other programmes to assure gender equity in provision
      and use of trichiasis surgery services.

PMID- 15489475
TI  - Management of primary rhegmatogenous retinal detachment with inferior breaks.
AB  - BACKGROUND: Rhegmatogenous retinal detachments (RRD) with inferior breaks are
      usually treated by scleral buckling (SB) or pars plana vitrectomy (PPV) or a
      combination of both methods. However, applying a SB during PPV may produce a risk
      of choroidal haemorrhage. Following a recent pilot study showing that such cases
      can be safely treated by PPV without SB the authors re-examined their management
      of RRD in which inferior breaks were present. METHODS: All patients had a
      detached vitreous and a complex configuration of retinal breaks. A case-control
      study was performed to analyse the surgical methods and results of PPV on 48
      consecutive patients with RRD associated with inferior breaks and 48 age/sex
      matched controls who underwent PPV for RRD without inferior breaks. Exclusion
      criteria were giant retinal tears, retinal dialysis, trauma, proliferative
      vitreoretinopathy (PVR) grade B or higher, schisis detachments, and eyes that had
      been operated previously for RRD. A simple algorithm was followed to manage
      patients with inferior breaks. All patients underwent a standard three port PPV
      with intraocular gas tamponade without supplementary SB. Patients were asked to
      posture face up or right or left side down for 1 week. RESULTS: 39 of the 48
      patients (81.3%) with inferior breaks were treated successfully with one
      operation. 41 of 48 patients (85.4%) control patients achieved primary success.
      The final success rate was 95.8% in both groups. There was no statistical
      difference between the two groups. When all the cases of RRD were analysed
      (including external plomb/non-drain procedures) the primary success rate was 89%
      and final success rate 97.5%. CONCLUSIONS: This study has shown that acceptable
      success rates can be achieved using PPV alone to treat RRD with inferior breaks.
      Complications are minimised and patients in this high risk group have an 81%
      chance of primary success. Pars plana vitrectomy and gas will successfully
      reattach the retina and a supplementary SB, to support the inferior retina, is
      unnecessary as the intraocular gas, and face up or, right or left side down
      positioning will tamponade breaks satisfactorily.

PMID- 15489476
TI  - Vitrectomy and gas for inferior break retinal detachments: are the results
      comparable to vitrectomy, gas, and scleral buckle?
AB  - AIMS: To compare the success rates of vitrectomy and gas with vitrectomy, gas,
      and buckle in the treatment of inferior break retinal detachments. METHODS: A
      retrospective case note review of 86 patients who presented with inferior break
      retinal detachments was carried out. An inferior break was defined as a horseshoe
      tear present between 4 and 8 o'clock. Patients were analysed in two groups; group
      A consisted of 41 patients who underwent a vitrectomy and gas, group B consisted
      of 45 patients who underwent a vitrectomy, gas, and scleral buckle. The features
      of the retinal detachment, peroperative and postoperative complications, and
      outcomes of treatment were recorded for each patient. RESULTS: The primary
      anatomical success rate at 3 months was 89% in group A versus 73% in group B (p =
      0.11). There was no statistical difference in the complication rate between the
      two groups (p = 0.819). The most common cause of treatment failure was
      proliferative vitreoretinopathy, 20% (n = 9) in group B compared with 5% (n = 2)
      in group A and this reached statistical significance (p = 0.0159). There was a
      higher rate of epiretinal membrane development in group B (p = 0.0004). The final
      attachment rate was not statistically different between the two groups, 95% (39)
      in group A and 93% (42) in group B (p = 1.0). CONCLUSION: Vitrectomy and gas
      without the application of a scleral buckle may be used to safely treat inferior
      break retinal detachments. It may be used as an alternative to vitrectomy, gas,
      and buckle which has an increased risk of choroidal haemorrhage, requires a
      longer operating time, and has all the associated complications of a scleral
      buckle.

PMID- 15489477
TI  - Treatment of thyroid associated ophthalmopathy with periocular injections of
      triamcinolone.
AB  - AIM: To evaluate the efficacy of periocular triamcinolone acetonide for the
      treatment of thyroid associated ophthalmopathy (TAO), and the presence of ocular
      or systemic adverse effects. METHODS: A multicentre prospective pilot study was
      performed on patients diagnosed with Graves' ophthalmopathy less than 6 months
      before entry to the study. Patients were admitted to the study and were
      randomised into two groups: treatment and control. The treatment group received
      four doses of 20 mg of triamcinolone acetate 40 mg/ml in a peribulbar injection
      to the inferolateral orbital quadrant. Both groups were evaluated by measuring
      the area of binocular vision without diplopia on a Goldmann perimeter and the
      size of the extraocular muscles on computed tomography (CT) scans.
      Ophthalmological and systemic examinations were done to rule out ocular and
      systemic adverse effects. Follow up was 6 months for both groups. RESULTS: 50
      patients were eligible for the study. 41 patients completed the study. There was
      an increase in the area of binocular vision without diplopia in the treatment
      group (Sigma initial: mean 231.1 (SD 99.9) and final absolute change, mean 107.1
      (SD 129.0)) compared to the control group (Sigma initial: mean 350.7 (SD 86.5)
      and final absolute change, mean -4.5 (SD 67.6)). The sizes of the extraocular
      muscles were reduced in the treatment group (mean (inferior rectus initial
      values): 1.3 (0.7), final percentage change: -13.2 (25.7), medial rectus initial
      values: 1.2 (0.6), final percentage change: -8.2 (20.7), superior rectus-levator
      palpebrae initial values: 1.2 (0.6), final percentage change: -9.5 (29.1),
      lateral rectus initial values: 1.0 (0.4), final percentage change: -11.5 (20.6))
      compared to the control group (inferior rectus initial values: 0.9 (0.3), final
      percentage change: -4.0 (21.5), medial rectus initial values: 0.9 (0.3), final
      percentage change: 0.6 (22.4), superior rectus-levator palpebrae initial values:
      0.9 (0.3), final percentage change: 12.5 (37.5), lateral rectus initial values:
      0.9 (0.4), final percentage change: -0.5 (31.6)). Both measurements (degree of
      diplopia and muscle thickness) were statistically significant between groups
      (initial - final). No systemic or ocular adverse effects were found. CONCLUSIONS:
      Triamcinolone administered as a periocular injection is effective in reducing
      diplopia and the sizes of extraocular muscles in TAO ophthalmopathy of recent
      onset. This form of treatment is not associated with systemic or ocular side
      effects.

PMID- 15489478
TI  - Optotype acuity and re-operation rate after unilateral cataract surgery during
      the first 6 months of life with or without IOL implantation.
AB  - AIMS: To compare optotype acuities and re-operation rates in children corrected
      with a contact lens (CL) compared with an intraocular lens (IOL) following
      unilateral cataract extraction during infancy in a non-randomised, retrospective
      case series. METHODS: 25 infants with a unilateral congenital cataract underwent
      cataract surgery with (IOL group, n = 12) or without (CL group, n = 13) IOL
      implantation when <7 months of age. Optotype acuities were assessed in 19 of
      these children at a mean age of 4.3 years (range 3.3-5.5 years). The number of re
      operations were assessed in 21 children. RESULTS: The visual acuity results were
      similar in the two treatment groups (p = 0.99); however, two of the four (50%)
      children in the IOL group compared with two of the seven (28%) children in the CL
      group undergoing surgery during the first 6 weeks of life had 20/40 or better
      visual acuity. The children in the IOL group had more re-operations than the
      children in the CL group (mean 1.1 v 0.36). Most of the re-operations in the IOL
      group were membranectomies performed during the first year of life (median 8.0
      months) whereas all of the re-operations in the CL group were the implantation of
      a secondary IOL later in childhood (mean 2.2 years). CONCLUSION: Optotype
      acuities were similar for the children corrected with a CL compared with IOL,
      while the children in the IOL group underwent more re-operations .

PMID- 15489479
TI  - Persistency and treatment failure in newly diagnosed open angle glaucoma patients
      in the United Kingdom.
AB  - AIM: To determine utilisation patterns and calculate treatment failure and
      discontinuation rates in patients with open angle glaucoma treated in the United
      Kingdom with any of six groups of intraocular pressure (IOP) lowering agents.
      METHODS: The UK General Practice Research Database was used to identify newly
      diagnosed (after 1 January 1997) open angle glaucoma patients who were naive to
      therapy with any of six index drug groups: carbonic anhydrase inhibitors,
      latanoprost, miotics, sympathomimetics, timolol, and other (non-timolol) beta
      blockers. Analyses included drug treatment data for 1 year following diagnosis.
      Outcomes were (1) time to therapy failure, defined as either change in index drug
      (replacement or addition of therapy) or patient referral for surgery, and (2)
      time to therapy discontinuation, defined as either therapy failure or no refill
      of the index drug in a period twice that covered by the first prescription fill.
      Cox proportional hazard regression and Kaplan-Meier and life table methods were
      used to compare groups. RESULTS: Among the 2001 eligible patients, a beta blocker
      other than timolol was the most widely prescribed (42%), followed by timolol
      (32%), carbonic anhydrase inhibitors (10%), and latanoprost (7%). Compared to
      latanoprost, those treated with any alternative agent were significantly more
      likely to fail (p < or = 0.005 for each comparison) and to discontinue (p < or =
      0.05 for each comparison) therapy. Failure rates ranged from 13% (latanoprost) to
      45% (sympathomimetics), and discontinuation rates ranged from 30% (latanoprost)
      to 63% (miotics). CONCLUSION: Latanoprost treated patients demonstrated lower
      rates of therapy failure and therapy discontinuation compared with patients
      treated with other widely used IOP lowering medications, including beta blockers.

PMID- 15489480
TI  - The effect of corneal thickness on intraocular pressure measurement in patients
      with corneal pathology.
AB  - BACKGROUND/AIM: To compare intraocular pressure (IOP) measurements taken by the
      Goldmann applanation tonometer, the Tono-Pen and the ocular blood flow
      pneumotonometer in eyes with varying central corneal thickness (CCT) due to
      penetrating keratoplasty (PK), keratoconus (KC), and Fuchs' endothelial dystrophy
      (FED). METHODS: IOP was measured with the Goldmann applanation tonometer, Tono
      Pen XL, and OBF pneumotonometer in 127 eyes with the following corneal
      abnormalities. There were 56 eyes that had undergone PK, 37 eyes with KC, and 34
      eyes with FED. CCT was measured using an ultrasound pachymeter after IOP
      determinations had been made. RESULTS: Mean IOP measurements in all three patient
      groups were significantly higher when measured by OBF pneumotonometer. Linear
      regression analysis showed that patients with FED had a significant increase in
      IOP with increasing CCT of 0.18 mm Hg/10 microm using the Goldmann tonometer,
      0.15 mm Hg/10 microm with the Tono-Pen, and 0.26 mm Hg/10 microm with the OBF
      pneumotonometer. In patients with KC and after PK, linear regression analysis did
      not show a significant effect of CCT on IOP. A multivariate linear regression
      model controlling for age, sex, graft size, and patient group, showed that the
      effect of CCT on IOP for Tono-Pen (0.13 mm Hg/10 microm CCT) and Goldmann (0.14
      mm Hg/10 microm CCT) were significantly lower than for the OBF pneumotonometer
      (0.26 mm Hg/10 microm CCT). CONCLUSIONS: This study found that mean IOP
      measurements using the OBF pneumotonometer were significantly higher than those
      made using the Goldmann applanation tonometer or Tono-Pen in eyes with a variety
      of cornel pathologies. The OBF pneumotonometer was found to be most affected by
      variation in CCT. For all three instruments, the relation between IOP and CCT
      depended on the corneal pathology and was greatest for FED.

PMID- 15489481
TI  - The fellow eye of patients with phakic rhegmatogenous retinal detachment from
      atrophic holes of lattice degeneration without posterior vitreous detachment.
AB  - BACKGROUND: Primary phakic rhegmatogenous retinal detachment (RRD) without
      posterior vitreous detachment (PVD) represents a unique clinical entity that
      behaves differently from RRD associated with PVD. While previous studies have
      reported the long term findings in the fellow eye of patients with RRD and PVD,
      the outcome of the fellow eye of patients with RRD without PVD is not known.
      METHODS: Consecutive patients with RRD not associated with PVD were studied
      retrospectively. The authors evaluated the fellow eye for retinal detachment or
      other vision threatening pathology. RESULTS: 27 patients (mean age 32 years) were
      studied with follow up of between 9 and 326 months (mean 111 months). 24 (89%)
      were myopic. Bilateral retinal detachment occurred in eight patients (30%). On
      initial examination, 17 patients (63%) had retinal findings (including lattice
      degeneration, atrophic holes, and/or cystic retinal tufts) in the fellow eye that
      might predispose them to retinal detachment. 14 vision threatening events or
      diagnoses occurred (nine of which were rhegmatogenous in nature) in the fellow
      eye including eight retinal detachments, one traumatic PVD without retinal tears,
      one retinal tear after PVD, one diagnosis of pigmentary glaucoma needing
      trabeculectomy, two visually significant cataracts, and one diagnosis of
      chorioretinitis. 23 patients (85%) maintained visual acuity better than 20/50,
      with most retaining 20/20 vision in the fellow eye. CONCLUSIONS: Patients who
      experience RRD without PVD are at risk of developing vision threatening events in
      the contralateral eye and, as such, the fellow eye should be followed carefully.

PMID- 15489482
TI  - Reduction of ocular muscle power by splitting of the rectus muscle I:
      biomechanics.
AB  - BACKGROUND/AIM: Based on mechanical considerations, the authors have developed a
      new approach to weakening oculomotor muscles. They present the biomechanical
      considerations that have encouraged them to explore this approach, and compare it
      with existing surgical techniques. Results of application to patients are given
      in the companion paper, and do not require an analytical understanding of the
      underlying mechanics. METHODS: Using a simple biomechanical model for the
      oculomotor system and vector component analysis, the eye position dependent
      torque exerted by extraocular muscles on the eyeball was investigated. This model
      was applied to the healthy eye, as well as to different surgical procedures
      (Cuppers' Fadenoperation, Y-split muscle recessions, botulinum toxin, and simple
      muscle recessions). CONCLUSION: These investigations suggest that a Y-split
      muscle recession is a simple and efficient way to weaken ocular rectus muscles.
      Compared to alternative surgical procedures, undesired radial forces that can
      lead to post-surgical complications can be kept to a minimum. The authors further
      speculate that their good results may in part be because of possible preservation
      of proprioceptive inputs from the insertion of the extraocular muscle.

PMID- 15489483
TI  - Reduction of ocular muscle torque by splitting of the rectus muscle II: technique
      and results.
AB  - AIM: To present the results of a new technique that the authors have developed to
      weaken the extraocular muscles. The biomechanics of this technique, which is
      termed "Y-split recession," are given in the companion paper. METHODS: A
      retrospective study, testing the effects of a new surgical technique on
      strabismus, nystagmus, and visual acuity. 228 patients (aged 6.8 (SD 6.0) years)
      with variable angle strabismus and nystagmus were treated by splitting and
      detaching two rectus muscles, and re-attaching the two halves at an angle of
      about 65 degrees to each other. Subjects were examined with the usual orthoptic
      tests immediately after the operation, and up to 96 months later. RESULTS: The
      operation reduced the strabismus, eliminated or weakened the nystagmus in primary
      position, and improved binocular vision and the development of visual acuity.
      Only minor side effects were observed. CONCLUSIONS: The Y-split recession can be
      used to reduce the torque for extraocular rectus muscles, and provides an
      alternative to "Cuppers Fadenoperation," recession, and similar procedures.

PMID- 15489484
TI  - Photodynamic therapy of circumscribed choroidal haemangioma.
AB  - AIM: To evaluate efficacy of verteporfin ocular photodynamic therapy (PDT) in
      treatment of 10 patients with a symptomatic circumscribed choroidal haemangioma.
      DESIGN: Prospective non-randomised, interventional case series and critical
      review of previously published studies. METHODS: 10 consecutive patients (seven
      primary, two failed transpupillary thermotherapy (TTT), and one failed external
      beam radiotherapy) with symptomatic circumscribed choroidal haemangioma were
      treated using verteporfin 6 mg/m2 given as an intravenous infusion over 10
      minutes. Diode laser (690 nm) with an intensity of 600 mW/cm2 for 83 seconds (50
      J/cm2) was applied 5 minutes after completion of infusion. Single or multiple
      partially overlapping spots were applied based on the tumour basal dimensions.
      Periodic follow up with ophthalmoscopy, ultrasonography, and angiographic studies
      was performed. RESULTS: All 10 patients showed evidence of regression with
      flattening of tumour, resolution of subretinal fluid, and reduction of choroidal
      vasculature on angiograms. The visual acuity either improved or remained stable
      in eight (80%) patients. Visual loss due to delayed choroidal atrophy was seen in
      two patients. CONCLUSIONS: Although verteporfin PDT is an effective treatment for
      management of symptomatic circumscribed choroidal haemangioma, delayed treatment
      related effects can lead to visual loss.

PMID- 15489485
TI  - An ultrasound based classification of periocular haemangiomas.
AB  - AIMS: To propose a classification system for periocular haemangiomas based on
      ultrasound evaluation. METHODS: Retrospective review of ultrasound images from
      children seen in the authors' unit with periocular haemangiomas. Static
      ultrasound images from 50 patients with periocular haemangiomas were reviewed as
      identified from a computerised database. Each haemangioma ultrasound image was
      classified into three categories: (1) preseptal only; (2) preseptal + extraconal;
      (3) preseptal + extraconal + intraconal. These were compared with the categories
      given to each patient at first presentation after dynamic scanning. RESULTS:
      Classification was possible from the static images in 44 (88%) cases. Of those
      classified 20 (45%) were preseptal only; 17 (39%) were preseptal + extraconal,
      and seven (16%) had an additional intraconal component. The classification in all
      44 cases was the same as that given at the time of presentation. In the small
      number of cases which went to surgery or had neuroimaging, the ultrasound
      classification was confirmed. CONCLUSIONS: Ultrasound classification was not
      difficult to perform and no child needed sedation or general anaesthesia for this
      exam. Ultrasound anatomical classification is an important first step in
      determining appropriate treatment of periocular haemangiomas. The authors present
      what they believe to be the first such classification.

PMID- 15489486
TI  - Epiphora as a side effect of topical mitomycin C.
AB  - AIM: To report symptoms and findings of lacrimal duct malfunction after topical
      mitomycin C (MMC) for conjunctival neoplasia. METHODS: 14 consecutive patients
      treated with 1-6 cycles of topical 0.04% MMC four times daily for periods of 2
      weeks were interviewed about symptoms of lacrimal duct malfunction. Patients who
      complained of tearing had examination of the puncta and canaliculi including
      probing and lacrimal duct irrigation. RESULTS: Nine patients complained of
      epiphora after topical MMC. Three of these patients had normal puncta and
      canaliculi, patent to irrigation. In these patients epiphora ceased spontaneously
      after probing and irrigation. The additional six patients had stenosis of the
      punctum (n = 3), the common canaliculus (n = 1), both puncta and both canaliculi
      (n = 1) and complete occlusion of the lower canaliculus (n = 1). CONCLUSION:
      Obstruction of the puncta or canaliculi is not an infrequent event after topical
      0.04% MMC.

PMID- 15489487
TI  - Mitomycin C for pterygium: long term evaluation.
AB  - AIM: To evaluate long term complications after pterygium excision with mitomycin
      C (MMC) application. DESIGN: Prospective non-comparative interventional case
      series. PARTICIPANTS: Ninety nine patients who underwent pterygium surgery and
      participated in a controlled study for efficacy of MMC for pterygium surgery
      between 1989 and 1994. METHODS: Patients who were located and agreed to come for
      examination underwent a complete eye examination. The bare sclera area, in
      particular, was examined for possible complications. The main outcome measures
      were anatomical findings in area of MMC application. RESULTS: Forty three eyes of
      43 patients were examined. Sixty three per cent of patients had pterygium surgery
      with intraoperative application of 0.02% MMC for 5 minutes and 37% of patients
      received MMC 1% or 2% drops four times daily for 2 weeks postoperatively. In
      three patients, pterygium recurred within 18 months. The only complication was
      mild conjunctival avascularity in areas of pterygium excision in 30% of patients.
      CONCLUSION: Long term evaluation revealed that the use of MMC in pterygium
      surgery is safe, but for a strict selection of patients, controlled use of MMC
      and long term follow up are required.

PMID- 15489488
TI  - Ophthalmological manifestations in segmental neurofibromatosis type 1.
AB  - AIMS: To study the ophthalmological manifestations in individuals with the
      typical features of neurofibromatosis type 1 (NF1) circumscribed to one or more
      body segments, usually referred to as segmental NF1. METHODS: Visual acuity and
      colour tests, visual field examination, slit lamp biomicroscopy of the anterior
      segment, and a detailed examination of the retina by indirect ophthalmoscopy were
      performed at diagnosis and follow up in 72 consecutive subjects (29 males, 43
      females; aged 1-64 years; mean age 14.6 years) seen at the university departments
      of paediatrics in Catania and Rome, Italy, during years 1990-2003, who had in
      restricted body areas: (1) typical pigmentary manifestations of NF1 (cafe au lait
      spots and freckling) only (n = 48); (2) NF1 pigmentary manifestations and
      neurofibromas alone (n = 2); (3) neurofibromas only (n = 15); and (4) plexiform
      neurofibromas only (n = 7). RESULTS: None of the 72 patients had Lisch nodules in
      the iris irrespective of age at eye examination or hypertelorism (a "minor" NF1
      feature) and none developed typical associated ophthalmological NF1
      complications. An additional child had an isolated optic pathways glioma (OPG),
      which behaved both biologically and radiographically as an NF1 associated OPG.
      CONCLUSIONS: This represents the first systematic study reporting on eye
      involvement in the largest series of individuals at different ages having
      segmental NF1. As one of the postulated mechanisms to explain segmental NF1 is
      somatic mosaicism for the NF1 gene (so far demonstrated only in two patients) the
      present findings could be explained either by the fact that the eye is too far
      from the mutated area with NF1 lesions in most cases or by the NF1 (or other
      "predisposing" or "cooperating") gene mutation restricted to too few cellular
      clones or to tissues embryologically different from the eye.

PMID- 15489489
TI  - Incremental nature of anterior eye grading scales determined by objective image
      analysis.
AB  - AIM: To use previously validated image analysis techniques to determine the
      incremental nature of printed subjective anterior eye grading scales. METHODS: A
      purpose designed computer program was written to detect edges using a 3 x 3
      kernal and to extract colour planes in the selected area of an image. Annunziato
      and Efron pictorial, and CCLRU and Vistakon-Synoptik photographic grades of
      bulbar hyperaemia, palpebral hyperaemia roughness, and corneal staining were
      analysed. RESULTS: The increments of the grading scales were best described by a
      quadratic rather than a linear function. Edge detection and colour extraction
      image analysis for bulbar hyperaemia (r2 = 0.35-0.99), palpebral hyperaemia (r2 =
      0.71-0.99), palpebral roughness (r2 = 0.30-0.94), and corneal staining (r2 = 0.57
      0.99) correlated well with scale grades, although the increments varied in
      magnitude and direction between different scales. Repeated image analysis
      measures had a 95% confidence interval of between 0.02 (colour extraction) and
      0.10 (edge detection) scale units (on a 0-4 scale). CONCLUSION: The printed
      grading scales were more sensitive for grading features of low severity, but
      grades were not comparable between grading scales. Palpebral hyperaemia and
      staining grading is complicated by the variable presentations possible. Image
      analysis techniques are 6-35 times more repeatable than subjective grading, with
      a sensitivity of 1.2-2.8% of the scale.

PMID- 15489490
TI  - Silicone oil concentrates fibrogenic growth factors in the retro-oil fluid.
AB  - AIM: To determine whether silicone oil concentrates protein and growth factors in
      the retro-oil fluid. METHODS: A laboratory analysis of intraocular fluid and
      vitreous specimens obtained from patients undergoing removal of silicone oil,
      revision vitrectomy, or primary vitrectomy for macular hole, proliferative
      vitreoretinopathy (PVR), or retinal detachment. Patients were prospectively
      recruited from routine vitreoretinal operating lists. Vitreous cavity fluid and
      vitreous samples were analysed for the presence of transforming growth factor
      beta (TGF-beta2), basic fibroblast growth factor (bFGF), interleukin 6 (IL-6),
      and total protein using either commercially available enzyme linked immunosorbent
      assays (ELISA) or protein assay kits. RESULTS: The median levels of bFGF, IL-6,
      and protein in the retro-oil fluid were raised (p<0.05) compared to all the other
      vitreous and vitreous cavity fluid samples. bFGF, IL-6, and protein levels were
      raised in PVR vitreous compared to non-PVR vitreous. TGF-beta2 levels were not
      significantly raised in retro-oil fluid or in PVR vitreous. CONCLUSIONS: The
      concentration of fibrogenic (bFGF) and inflammatory (IL-6) growth factors and
      protein is raised in retro-silicone oil fluid. This may contribute to the process
      of retro-oil perisilicone proliferation and subsequent fibrocellular membrane
      formation.

PMID- 15489491
TI  - Enhanced low vision rehabilitation for people with age related macular
      degeneration: a randomised controlled trial.
AB  - AIM: To compare the effectiveness of three models of low vision rehabilitation
      for people with age related macular degeneration (AMD) referred for low vision
      rehabilitation (LVR): (a) an enhanced low vision rehabilitation model (ELVR)
      including supplementary home based low vision rehabilitation; (b) conventional
      low vision rehabilitation (CLVR) based in a hospital clinic; (c) CLVR with home
      visits that did not include rehabilitation (CELVR), intended to act as a control
      for the additional contact time with ELVR. METHOD: A single centre parallel group
      randomised controlled trial in participants' homes and the low vision clinic,
      Manchester Royal Eye Hospital. People referred for LVR with a primary diagnosis
      of AMD and visual acuity worse than 6/18 in both eyes and equal to or better than
      1/60 in the better eye. The main outcome measures were vision specific quality of
      life (QoL) (primary outcome, VCM1) and generic health related QoL (SF-36);
      psychological adjustment to vision loss; measured task performance; restriction
      in everyday activities; use of low vision aids (LVAs). RESULTS: 226 participants
      were recruited (median age 82 years); 194 completed the trial (86%). Except for
      SF-36 physical and mental component summary scores, arms did not differ
      significantly for any of the outcomes. Differences for the VCM1 were ELVR v CLVR,
      0.06 (95% CI to 0.17 to 0.30, p = 0.60); ELVR v CELVR, 0.12 (95% CI to 0.11 to
      0.34, p = 0.31); CELVR v CLVR, -0.05 (95% CI -0.29 to 0.18, p = 0.64).
      Differences for the SF-36 favoured CLVR compared to ELVR (ELVR v CLVR: physical =
      -6.05, 95% CI -10.2 to -1.91, p = 0.004; mental = -4.04, 95% CI -7.44 to -0.65, p
      = 0.02). At 12 months, 94% of participants reported using at least one LVA.
      CONCLUSION: ELVR was no more effective than CLVR. Researchers should be wary of
      proposing new LVR interventions without preliminary evidence of effectiveness,
      given the manifest lack of effectiveness of the model of enhanced LVR evaluated
      in the trial.

PMID- 15489492
TI  - Use of polyurethane with sustained release dexamethasone in delayed adjustable
      strabismus surgery.
AB  - AIM: To determine the effect of polyurethane film with sustained release
      dexamethasone (SRD) in delayed adjustable strabismus surgery. METHODS: A
      prospective, masked observer, controlled study was performed in rabbits. Thirty
      four rabbit eyes were divided into three groups. After recession of the superior
      rectus muscle (SRM), polyurethane film with or without SRD, or balanced salt
      solution was applied beneath and over SRM in the polyurethane-dexamethasone group
      (group P-D), polyurethane group (group P), and the control group (group C),
      respectively. Delayed adjustment was performed once on each SRM at 4 and 6 weeks
      postoperatively by a masked observer. The possible length to adjust and the
      necessary force required for the adjustment, as well as the degree of any
      adhesions, were also evaluated. RESULTS: In the control group, adjustment was
      impossible in all of the eyes at 4 and 6 weeks postoperatively. In group P-D,
      adjustment was possible in 11 out of 11 eyes (11/11) 4 weeks postoperatively and
      in 10/11 eyes 6 weeks postoperatively. In group P, adjustment was possible in
      9/11 eyes 4 weeks postoperatively and in 10/12 eyes 6 weeks postoperatively.
      CONCLUSIONS: Use of polyurethane film with and without SRD could delay adjustment
      in most eyes for up to 6 weeks postoperatively. Polyurethane is helpful for
      delaying adjustment in rabbit eyes until 6 weeks postoperatively without the need
      for frequent topical instillation of steroids.

PMID- 15489493
TI  - Neuro-ophthalmological disorders in HIV infected subjects with neurological
      manifestations.
AB  - AIMS: To determine the frequency and features of neuro-ophthalmological
      manifestations in neurologically symptomatic HIV infected patients and to assess
      whether or not the visual evoked potential (VEP) features in these patients
      differ from those of neurologically asymptomatic HIV infected patients. METHODS:
      Neuro-ophthalmological evaluation was performed in 166 neurologically symptomatic
      confirmed HIV positive patients, of whom 75 with normal ophthalmological
      examination were further studied by means of VEPs. The VEPs values were compared
      to those obtained from 53 other confirmed HIV positive subjects with neither
      ophthalmological nor neurological manifestations, who served as a comparison
      group and to the references values of our laboratory. RESULTS: An abnormal neuro
      ophthalmological examination was noted in 99/166 patients (60%). Eye movement
      disorders were present in 99 patients (51%). Visual field defects were detected
      in 39% of the patients. Optic neuropathy was noted in 31%, papilloedema in 27%
      and ocular motor nerve palsies in 26% of the patients. Toxoplasmosis and
      cryptococcosis were the most frequent associated pathologies, though in some
      patients the HIV itself was the presumed cause. VEPs were abnormal in 57% and 42%
      of patients with and without neurological manifestations, respectively. Compared
      to asymptomatic patients, symptomatic patients had a significantly increased mean
      latency; however, both groups had significant increase in mean latency compared
      to reference values. CONCLUSION: Neuro-ophthalmological manifestations are common
      in neurologically symptomatic HIV infected patients. Subclinical dysfunction in
      the visual pathways is a common phenomenon in both HIV infected patients with and
      without neurological symptoms, but neurologically symptomatic patients seem to
      have more damage in their visual pathways.

PMID- 15489494
TI  - Dynamic molecular resolution imaging of preocular fluid impressions.
AB  - AIM: The preocular fluid is renewed with molecules secreted by the underlying
      cells and with lacrimal gland secretions, while maintaining a stable surface
      topography. The authors tested the hypothesis that interactions between gelled
      and newly inserted mucins are the key to this stability. METHODS: Using atomic
      force microscopy, the authors studied the topography of the freshly isolated
      preocular fluid obtained by impression cytology. The effects of adding mucins to
      this impression were compared with adding mucins to a pure mucin macromolecular
      assembly as a single component control to the more complex preocular fluid. The
      control structure was built up by repeated addition of pure ocular mucin to a
      tethering surface. RESULTS: Imaging at molecular resolution showed a thin layer
      of superficial preocular fluid with an appearance consistent with a gel that was
      very flat, with surface roughness of approximately 0.1 nm. Mucin molecules
      adhering to a clean flat surface maintained their individual character when
      overlapping, whereas molecules integrating in the impression could not be
      followed individually. Both the preocular impression and the pure mucin assembly
      were stable under imaging for at least 90 minutes. The roughness of the pure
      mucin network decreased as more mucin was added. In contrast, there was a small
      increase in the roughness of the 2.25 microm2 area of impression over the 60
      minutes of continuous imaging, although locally there appeared to be infill of
      low height features. Disulphide bond breaking resulted in the collapse of the
      imaged structure in both the pure mucin control and the more complex ex vivo
      preocular impression. CONCLUSIONS: Polymeric mucins linked by disulphide bonds
      prevent or lessen loss of ocular surface material into the surrounding aqueous
      tears.

PMID- 15489495
TI  - Autologous serum eye drops for ocular surface disorders.
AB  - Tears have antimicrobial, nourishing, mechanical, and optical properties. They
      contain components such as growth factors, fibronectin, and vitamins to support
      proliferation, migration, and differentiation of the corneal and conjunctival
      epithelium. A lack of these epitheliotrophic factors--for example, in dry eye,
      can result in severe ocular surface disorders such as persistent epithelial
      defects. Recently, the use of autologous serum in the form of eye drops has been
      reported as a new treatment for severe ocular surface disorders. Serum eye drops
      may be produced as an unpreserved blood preparation. They are by nature non
      allergenic and their biomechanical and biochemical properties are similar to
      normal tears. In vitro cell culture experiments showed that corneal epithelial
      cell morphology and function are better maintained by serum than by
      pharmaceutical tear substitutes. Clinical cohort studies have reported its
      successful use for severe dry eyes and persistent epithelial defects. However,
      the protocols to prepare and use autologous serum eye drops varied considerably
      between the studies. As this can result in different biochemical properties
      protocol variations may also influence the epitheliotrophic effect of the
      product. Before the definitive role of serum eye drops in the management of
      severe ocular surface disease can be established in a large randomised controlled
      trial this has to be evaluated in more detail. In view of legislative
      restrictions and based upon the literature reviewed here a preliminary standard
      operating procedure for the manufacture of serum eye drops is proposed.

PMID- 15489496
TI  - Norrie disease and peripheral venous insufficiency.

PMID- 15489497
TI  - Spontaneous bilateral giant tears of the retinal pigment epithelium.

PMID- 15489498
TI  - Count and size of macular drusen correlated with the parafoveal annular reflex.

PMID- 15489499
TI  - Ocular findings as a presenting sign of hydroa vacciniforme.

PMID- 15489500
TI  - An unusual strategy for fixation in a patient with bilateral advanced age related
      macular disease.

PMID- 15489501
TI  - Potential complications of phakic IOLs.

PMID- 15489502
TI  - General enzymatic screens identify three new nucleotidases in Escherichia coli.
      Biochemical characterization of SurE, YfbR, and YjjG.
AB  - To find proteins with nucleotidase activity in Escherichia coli, purified unknown
      proteins were screened for the presence of phosphatase activity using the general
      phosphatase substrate p-nitrophenyl phosphate. Proteins exhibiting catalytic
      activity were then assayed for nucleotidase activity against various nucleotides.
      These screens identified the presence of nucleotidase activity in three
      uncharacterized E. coli proteins, SurE, YfbR, and YjjG, that belong to different
      enzyme superfamilies: SurE-like family, HD domain family (YfbR), and haloacid
      dehalogenase (HAD)-like superfamily (YjjG). The phosphatase activity of these
      proteins had a neutral pH optimum (pH 7.0-8.0) and was strictly dependent on the
      presence of divalent metal cations (SurE: Mn(2+) > Co(2+) > Ni(2+) > Mg(2+);
      YfbR: Co(2+) > Mn(2+) > Cu(2+); YjjG: Mg(2+) > Mn(2+) > Co(2+)). Further
      biochemical characterization of SurE revealed that it has a broad substrate
      specificity and can dephosphorylate various ribo- and deoxyribonucleoside 5'
      monophosphates and ribonucleoside 3'-monophosphates with highest affinity to 3'
      AMP. SurE also hydrolyzed polyphosphate (exopolyphosphatase activity) with the
      preference for short-chain-length substrates (P(20-25)). YfbR was strictly
      specific to deoxyribonucleoside 5'-monophosphates, whereas YjjG showed narrow
      specificity to 5'-dTMP, 5'-dUMP, and 5'-UMP. The three enzymes also exhibited
      different sensitivities to inhibition by various nucleoside di- and
      triphosphates: YfbR was equally sensitive to both di- and triphosphates, SurE was
      inhibited only by triphosphates, and YjjG was insensitive to these effectors. The
      differences in their sensitivities to nucleotides and their varied substrate
      specificities suggest that these enzymes play unique functions in the
      intracellular nucleotide metabolism in E. coli.

PMID- 15489503
TI  - The 1.8-A crystal structure of human tear lipocalin reveals an extended branched
      cavity with capacity for multiple ligands.
AB  - In contrast with earlier assumptions, which classified human tear lipocalin (Tlc)
      as an outlier member of the lipocalin protein family, the 1.8-A resolution
      crystal structure of the recombinant apoprotein confirms the typical eight
      stranded antiparallel beta-barrel architecture with an alpha-helix attached to
      it. The fold of Tlc most closely resembles the bovine dander allergen Bos d 2, a
      well characterized prototypic lipocalin, but also reveals similarity with beta
      lactoglobulin. However, compared with other lipocalin structures Tlc exhibits an
      extremely wide ligand pocket, whose entrance is formed by four partially
      disordered loops. The cavity deeply extends into the beta-barrel structure, where
      it ends in two distinct lobes. This unusual structural feature explains the known
      promiscuity of Tlc for various ligands, with chemical structures ranging from
      lipids and retinoids to the macrocyclic antibiotic rifampin and even to microbial
      siderophores. Notably, earlier findings of biological activity as a thiol
      protease inhibitor have no correspondence in the three-dimensional structure of
      Tlc, rather it appears that its proteolytic fragments could be responsible for
      this phenomenon. Hence, the present structural analysis sheds new light on the
      ligand binding activity of this functionally obscure but abundant human
      lipocalin.

PMID- 15489504
TI  - The myotonic dystrophy type 1 triplet repeat sequence induces gross deletions and
      inversions.
AB  - The capacity of (CTG.CAG)n and (GAA.TTC)n repeat tracts in plasmids to induce
      mutations in DNA flanking regions was evaluated in Escherichia coli. Long repeats
      of these sequences are involved in the etiology of myotonic dystrophy type 1 and
      Friedreich's ataxia, respectively. Long (CTG.CAG)n (where n = 98 and 175) caused
      the deletion of most, or all, of the repeats and the flanking GFP gene. Deletions
      of 0.6-1.8 kbp were found as well as inversions. Shorter repeat tracts (where n =
      0 or 17) were essentially inert, as observed for the (GAA.TTC)176-containing
      plasmid. The orientation of the triplet repeat sequence (TRS) relative to the
      unidirectional origin of replication had a pronounced effect, signaling the
      participation of replication and/or repair systems. Also, when the TRS was
      transcribed, the level of deletions was greatly elevated. Under certain
      conditions, 30-50% of the products contained gross deletions. DNA sequence
      analyses of the breakpoint junctions in 47 deletions revealed the presence of 1-8
      bp direct or inverted homologies in all cases. Also, the presence of non-B folded
      conformations (i.e. slipped structures, cruciforms, or triplexes) at or near the
      breakpoints was predicted in all cases. This genetic behavior, which was
      previously unrecognized for a TRS, may provide the basis for a new type of
      instability of the myotonic dystrophy protein kinase (DMPK) gene in patients with
      a full mutation.

PMID- 15489505
TI  - The DinI and RecX proteins are competing modulators of RecA function.
AB  - The DinI and RecX proteins of Escherichia coli both modulate the function of RecA
      protein, but have very different effects. DinI protein stabilizes RecA filaments,
      preventing disassembly but permitting assembly. RecX protein blocks RecA filament
      extension, which can lead to net filament disassembly. We demonstrate that both
      proteins can interact with the RecA filament, and propose that each can replace
      the other. The DinI/RecX displacement reactions are slow, requiring multiple
      minutes even when a large excess of the challenging protein is present. The
      effects of RecX protein on RecA filaments are manifest at lower modulator
      concentrations than the effects of DinI protein. Together, the DinI and RecX
      proteins constitute a new regulatory network. The two proteins compete directly
      as mainly positive (DinI) and negative (RecX) modulators of RecA function.

PMID- 15489506
TI  - Substitution of conserved residues within the active site alters the cleavage
      religation equilibrium of DNA topoisomerase I.
AB  - Eukaryotic DNA topoisomerase I (Top1p) catalyzes the relaxation of supercoiled
      DNA and constitutes the cellular target of camptothecin (CPT). Mutation of
      conserved residues in close proximity to the active site tyrosine (Tyr(727) of
      yeast Top1p) alters the DNA cleavage religation equilibrium, inducing drug
      independent cell lethality. Previous studies indicates that yeast Top1T722Ap and
      Top1N726Hp cytotoxicity results from elevated levels of covalent enzyme-DNA
      intermediates. Here we show that Top1T722Ap acts as a CPT mimetic by exhibiting
      reduced rates of DNA religation, whereas increased Top1N726Hp.DNA complexes
      result from elevated DNA binding and cleavage. We also report that the
      combination of the T722A and N726H mutations in a single protein potentiates the
      cytotoxic action of the enzyme beyond that induced by co-expression of the single
      mutants. Moreover, the addition of CPT to cells expressing the double
      top1T722A/N726H mutant did not enhance cell lethality. Thus, independent
      alterations in DNA cleavage and religation contribute to the lethal phenotype.
      The formation of distinct cytotoxic lesions was also evidenced by the different
      responses induced by low levels of these self-poisoning enzymes in isogenic
      strains defective for the Rad9 DNA damage checkpoint, processive DNA replication,
      or ubiquitin-mediated proteolysis. Substitution of Asn(726) with Phe or Tyr also
      produces self-poisoning enzymes, implicating stacking interactions in the
      increased kinetics of DNA cleavage by Top1N726Hp and Top1N726Fp. In contrast,
      replacing the amide side chain of Asn(726) with Gln renders Top1N726Qp resistant
      to CPT, suggesting that the orientation of the amide within the active site is
      critical for effective CPT binding.

PMID- 15489508
TI  - The enzymatic activities of the Werner syndrome protein are disabled by the amino
      acid polymorphism R834C.
AB  - The Werner syndrome protein, WRN, is a member of the RecQ family of DNA
      helicases. It possesses both 3'-->5' DNA helicase and 3'-->5' DNA exonuclease
      activities. Mutations in WRN are causally associated with a rare, recessive
      disorder, Werner syndrome (WS), distinguished by premature aging and genomic
      instability; all are reported to result in loss of protein expression. In
      addition to WS-linked mutations, single nucleotide polymorphisms, with
      frequencies that exceed those of WS-associated mutations, are also present in
      WRN. We have initiated studies to determine if six of these polymorphisms affect
      the enzymatic activities of WRN. We show that two common polymorphisms, F1074L
      and C1367R, and two infrequent polymorphisms, Q724L and S1079L, exhibit little
      change in activity relative to wild-type WRN; the polymorphism, T172P, shows a
      small but consistent reduction of activity. However, an infrequent polymorphism,
      R834C, located in the helicase domain dramatically reduces WRN helicase and
      helicase-coupled exonuclease activity. The structure of the E. coli helicase core
      suggests that R834 may be involved in interactions with ATP. As predicted,
      substitution of Arg with Cys interferes with ATP hydrolysis that is absolutely
      required for unwinding DNA. R834C thus represents the first missense amino acid
      polymorphism in WRN that nearly abolishes enzymatic activity while leaving
      expression largely unaffected.

PMID- 15489507
TI  - Functional characterization of rhodopsin monomers and dimers in detergents.
AB  - Rhodopsin (Rho) is a G protein-coupled receptor that initiates phototransduction
      in rod photoreceptors. High expression levels of Rho in the disc membranes of rod
      outer segments and the propensity of Rho to form higher oligomeric structures are
      evident from atomic force microscopy, transmission electron microscopy, and
      chemical cross-linking experiments. To explore the structural and functional
      properties of Rho in n-dodecyl-beta-maltoside, frequently used to purify
      heterologously expressed Rho and its mutants, we used gel filtration techniques,
      blue native gel electrophoresis, and functional assays. Here, we show that in
      micelles containing n-dodecyl-beta-maltoside at concentrations greater than 3 mM,
      Rho is present as a single monomer per detergent micelle. In contrast, in 12 mM 3
      [(3-cholamidopropyl)dimethyl-ammonio]-1-propanesulfonate (CHAPS), micelles
      contain mostly dimeric Rho. The cognate G protein transducin (Gt) appears to have
      a preference for binding to the Rho dimer, and the complexes fall apart in the
      presence of guanosine 5'-3-O-(thio)triphosphate. Cross-linked Rho dimers release
      the chromophore at a slower rate than monomers and are much more resistant to
      heat denaturation. Both Rho(*) monomers and dimers are capable of activating Gt,
      and both of them are phosphorylated by Rho kinase. Rho expressed in HEK293 cells
      is also readily cross-linked by a bifunctional reagent. These studies provide an
      explanation of how detergent influences the oligomer-dimermonomer equilibrium of
      Rho and describe the functional characterization of Rho monomers and dimers in
      detergent.

PMID- 15489509
TI  - Joint mapping of quantitative trait Loci for multiple binary characters.
AB  - Joint mapping for multiple quantitative traits has shed new light on genetic
      mapping by pinpointing pleiotropic effects and close linkage. Joint mapping also
      can improve statistical power of QTL detection. However, such a joint mapping
      procedure has not been available for discrete traits. Most disease resistance
      traits are measured as one or more discrete characters. These discrete characters
      are often correlated. Joint mapping for multiple binary disease traits may
      provide an opportunity to explore pleiotropic effects and increase the
      statistical power of detecting disease loci. We develop a maximum-likelihood
      method for mapping multiple binary traits. We postulate a set of multivariate
      normal disease liabilities, each contributing to the phenotypic variance of one
      disease trait. The underlying liabilities are linked to the binary phenotypes
      through some underlying thresholds. The new method actually maps loci for the
      variation of multivariate normal liabilities. As a result, we are able to take
      advantage of existing methods of joint mapping for quantitative traits. We treat
      the multivariate liabilities as missing values so that an expectation
      maximization (EM) algorithm can be applied here. We also extend the method to
      joint mapping for both discrete and continuous traits. Efficiency of the method
      is demonstrated using simulated data. We also apply the new method to a set of
      real data and detect several loci responsible for blast resistance in rice.

PMID- 15489510
TI  - Mutations that rescue the paralysis of Caenorhabditis elegans ric-8 (synembryn)
      mutants activate the G alpha(s) pathway and define a third major branch of the
      synaptic signaling network.
AB  - To identify hypothesized missing components of the synaptic G alpha(o)-G alpha(q)
      signaling network, which tightly regulates neurotransmitter release, we undertook
      two large forward genetic screens in the model organism C. elegans and focused
      first on mutations that strongly rescue the paralysis of ric-8(md303) reduction
      of-function mutants, previously shown to be defective in G alpha(q) pathway
      activation. Through high-resolution mapping followed by sequence analysis, we
      show that these mutations affect four genes. Two activate the G alpha(q) pathway
      through gain-of-function mutations in G alpha(q); however, all of the remaining
      mutations activate components of the G alpha(s) pathway, including G alpha(s),
      adenylyl cyclase, and protein kinase A. Pharmacological assays suggest that the G
      alpha(s) pathway-activating mutations increase steady-state neurotransmitter
      release, and the strongly impaired neurotransmitter release of ric-8(md303)
      mutants is rescued to greater than wild-type levels by the strongest G alpha(s)
      pathway activating mutations. Using transgene induction studies, we show that
      activating the G alpha(s) pathway in adult animals rapidly induces hyperactive
      locomotion and rapidly rescues the paralysis of the ric-8 mutant. Using cell
      specific promoters we show that neuronal, but not muscle, G alpha(s) pathway
      activation is sufficient to rescue ric-8(md303)'s paralysis. Our results appear
      to link RIC-8 (synembryn) and a third major G alpha pathway, the G alpha(s)
      pathway, with the previously discovered G alpha(o) and G alpha(q) pathways of the
      synaptic signaling network.

PMID- 15489512
TI  - Chromosome identification and nomenclature of Sorghum bicolor.
AB  - Linkage group identities and homologies were determined for metaphase chromosomes
      of Sorghum bicolor (2n = 20) by FISH of landed BACs. Relative lengths of
      chromosomes in FISH-karyotyped metaphase spreads of the elite inbred BTx623 were
      used to estimate the molecular size of each chromosome and to establish a size
      based nomenclature for sorghum chromosomes (SBI-01-SBI-10) and linkage groups (LG
      01 to LG-10). Lengths of arms were determined to orient linkage groups relative
      to a standard karyotypic layout (short arms at top). The size-based nomenclature
      for BTx623 represents a reasonable choice as the standard for a unified
      chromosome nomenclature for use by the sorghum research community.

PMID- 15489511
TI  - Convergent, RIC-8-dependent Galpha signaling pathways in the Caenorhabditis
      elegans synaptic signaling network.
AB  - We used gain-of-function and null synaptic signaling network mutants to
      investigate the relationship of the G alpha(q) and G alpha(s) pathways to
      synaptic vesicle priming and to each other. Genetic epistasis studies using G
      alpha(q) gain-of-function and null mutations, along with a mutation that blocks
      synaptic vesicle priming and the synaptic vesicle priming stimulator phorbol
      ester, suggest that the G alpha(q) pathway generates the core, obligatory signals
      for synaptic vesicle priming. In contrast, the G alpha(s) pathway is not required
      for the core priming function, because steady-state levels of neurotransmitter
      release are not significantly altered in animals lacking a neuronal G alpha(s)
      pathway, even though these animals are strongly paralyzed as a result of
      functional (nondevelopmental) defects. However, our genetic analysis indicates
      that these two functionally distinct pathways converge and that they do so
      downstream of DAG production. Further linking the two pathways, our epistasis
      analysis of a ric-8 null mutant suggests that RIC-8 (a receptor-independent G
      alpha guanine nucleotide exchange factor) is required to maintain both the G
      alpha(q) vesicle priming pathway and the neuronal G alpha(s) pathway in a
      functional state. We propose that the neuronal G alpha(s) pathway transduces
      critical positional information onto the core G alpha(q) pathway to stabilize the
      priming of selected synapses that are optimal for locomotion.

PMID- 15489513
TI  - Molecular cytogenetic maps of sorghum linkage groups 2 and 8.
AB  - To integrate genetic, physical, and cytological perspectives of the Sorghum
      bicolor genome, we selected 40 landed bacterial artificial chromosome (BAC)
      clones that contain different linkage map markers, 21 from linkage group 2 (LG
      02) and 19 from linkage group 8 (LG-08). Multi-BAC probe cocktails were
      constructed for each chromosome from the landed BACs, which were also
      preevaluated for FISH signal quality, relative position, and collective
      chromosome coverage. Comparison to the corresponding linkage map revealed full
      concordance of locus order between cytological and prior segregation analyses.
      The pericentromeric heterochromatin constituted a large quasi-uniform block in
      each bivalent and was especially large in the bivalent corresponding to LG-08.
      Centromere positions in LG-02 and LG-08 were progressively delimited using FISH
      to identify landed BACs for which the FISH signals visibly flanked the
      centromere. Alignment of linkage and cytological maps revealed that
      pericentromeric heterochromatin of these sorghum chromosomes is largely devoid of
      recombination, which is mostly relegated to the more distal regions, which are
      largely euchromatic. This suggests that the sorghum genome is thus even more
      amenable to physical mapping of genes and positional cloning than the C-value
      alone might suggest. As a prelude to positional cloning of the fertility
      restorer, Rf1, FISH of BAC clones flanking the Rf1 locus was used to delimit the
      chromosomal position of the gene. FISH of BACs that contain the most proximal
      linkage markers enabled localization of Rf1 to a approximately 0.4-Mbp
      euchromatic region of LG-08. Cytogenetic analyses of Rf1 and other trait loci
      will aid in assessing the feasibility of positional cloning and help formulate
      strategies required for cloning this and other agriculturally critical genes.

PMID- 15489514
TI  - Genome-wide screen for genes with effects on distinct iron uptake activities in
      Saccharomyces cerevisiae.
AB  - We screened a collection of 4847 haploid knockout strains (EUROSCARF collection)
      of Saccharomyces cerevisiae for iron uptake from the siderophore ferrioxamine B
      (FOB). A large number of mutants showed altered uptake activities, and a few
      turned yellow when grown on agar plates with added FOB, indicating increased
      intracellular accumulation of undissociated siderophores. A subset consisting of
      197 knockouts with altered uptake was examined further for regulated activities
      that mediate cellular uptake of iron from other siderophores or from iron salts.
      Hierarchical clustering analysis grouped the data according to iron sources and
      according to mutant categories. In the first analysis, siderophores grouped
      together with the exception of enterobactin, which grouped with iron salts,
      suggesting a reductive pathway of iron uptake for this siderophore. Mutant
      groupings included three categories: (i) high-FOB uptake, high reductase, low
      ferrous transport; (ii) isolated high- or low-FOB transport; and (iii) induction
      of all activities. Mutants with statistically altered uptake activities included
      genes encoding proteins with predominant localization in the secretory pathway,
      nucleus, and mitochondria. Measurements of different iron-uptake activities in
      the yeast knockout collection make possible distinctions between genes with
      general effects on iron metabolism and those with pathway-specific effects.

PMID- 15489515
TI  - Long-term experimental evolution in Escherichia coli. XII. DNA topology as a key
      target of selection.
AB  - The genetic bases of adaptation are being investigated in 12 populations of
      Escherichia coli, founded from a common ancestor and serially propagated for
      20,000 generations, during which time they achieved substantial fitness gains.
      Each day, populations alternated between active growth and nutrient exhaustion.
      DNA supercoiling in bacteria is influenced by nutritional state, and DNA topology
      helps coordinate the overall pattern of gene expression in response to
      environmental changes. We therefore examined whether the genetic controls over
      supercoiling might have changed during the evolution experiment. Parallel changes
      in topology occurred in most populations, with the level of DNA supercoiling
      increasing, usually in the first 2000 generations. Two mutations in the topA and
      fis genes that control supercoiling were discovered in a population that served
      as the focus for further investigation. Moving the mutations, alone and in
      combination, into the ancestral background had an additive effect on
      supercoiling, and together they reproduced the net change in DNA topology
      observed in this population. Moreover, both mutations were beneficial in
      competition experiments. Clonal interference involving other beneficial DNA
      topology mutations was also detected. These findings define a new class of
      fitness-enhancing mutations and indicate that the control of DNA supercoiling can
      be a key target of selection in evolving bacterial populations.

PMID- 15489516
TI  - Distinct roles for the Saccharomyces cerevisiae mismatch repair proteins in
      heteroduplex rejection, mismatch repair and nonhomologous tail removal.
AB  - The Saccharomyces cerevisiae mismatch repair (MMR) protein MSH6 and the SGS1
      helicase were recently shown to play similarly important roles in preventing
      recombination between divergent DNA sequences in a single-strand annealing (SSA)
      assay. In contrast, MMR factors such as Mlh1p, Pms1p, and Exo1p were shown to not
      be required or to play only minimal roles. In this study we tested mutations that
      disrupt Sgs1p helicase activity, Msh2p-Msh6p mismatch recognition, and ATP
      binding and hydrolysis activities for their effect on preventing recombination
      between divergent DNA sequences (heteroduplex rejection) during SSA. The results
      support a model in which the Msh proteins act with Sgs1p to unwind DNA
      recombination intermediates containing mismatches. Importantly, msh2 mutants that
      displayed separation-of-function phenotypes with respect to nonhomologous tail
      removal during SSA and heteroduplex rejection were characterized. These studies
      suggest that nonhomologous tail removal is a separate function of Msh proteins
      that is likely to involve a distinct DNA binding activity. The involvement of
      Sgs1p in heteroduplex rejection but not nonhomologous tail removal further
      illustrates that subsets of MMR proteins collaborate with factors in different
      DNA repair pathways to maintain genome stability.

PMID- 15489517
TI  - The generation of cloned Drosophila melanogaster.
AB  - We report here the first successful use of embryonic nuclear transfer to create
      viable adult Drosophila melanogaster clones. Given the generation time, cost
      effectiveness, and relative ease of embryonic nuclear transplant in Drosophila,
      this method can provide an opportunity to further study the constraints on
      development imposed by transplanting determined or differentiated nuclei.

PMID- 15489518
TI  - MuDR transposase increases the frequency of meiotic crossovers in the vicinity of
      a Mu insertion in the maize a1 gene.
AB  - Although DNA breaks stimulate mitotic recombination in plants, their effects on
      meiotic recombination are not known. Recombination across a maize a1 allele
      containing a nonautonomous Mu transposon was studied in the presence and absence
      of the MuDR-encoded transposase. Recombinant A1' alleles isolated from a1
      mum2/a1::rdt heterozygotes arose via either crossovers (32 CO events) or
      noncrossovers (8 NCO events). In the presence of MuDR, the rate of COs increased
      fourfold. This increase is most likely a consequence of the repair of MuDR
      induced DNA breaks at the Mu1 insertion in a1-mum2. Hence, this study provides
      the first in vivo evidence that DNA breaks stimulate meiotic crossovers in
      plants. The distribution of recombination breakpoints is not affected by the
      presence of MuDR in that 19 of 24 breakpoints isolated from plants that carried
      MuDR mapped to a previously defined 377-bp recombination hotspot. This result is
      consistent with the hypothesis that the DNA breaks that initiate recombination at
      a1 cluster at its 5' end. Conversion tracts associated with eight NCO events
      ranged in size from <700 bp to >1600 bp. This study also establishes that MuDR
      functions during meiosis and that ratios of CO/NCO vary among genes and can be
      influenced by genetic background.

PMID- 15489519
TI  - A torrid zone on mouse chromosome 1 containing a cluster of recombinational
      hotspots.
AB  - Within the 2.38-Mb Ath1 region of mouse chromosome 1, 42 of 45 genetic crossovers
      from crosses between C57BL/6J (B6) and either C3H/HeJ (H) or Mus spretus (SPRET)
      occurred in four zones (A-D); zone A, 100 kb long, contained a cluster of at
      least four recombination hotspots. F1 sperm assays indicate that within this
      "torrid zone" the most active hotspot (A3) can initiate recombination on H and
      SPRET but not B6 chromosomes. The A3 DNA sequence contains a (G/C)TTT repeat,
      long stretches of A or T, and a cyclic variation in AT content. Recombination was
      drastically reduced in a cross between B6 and a B6.SPRET Ath1 congenic strain,
      but was unaffected in a B6 x B6.H Ath1 congenic cross. Similar nonrandom
      clustering of hotspots has been observed in yeast and the major
      histocompatibility complexes of human and mouse. To the extent that torrid zones
      are a general feature of mammalian genomes, they have considerable implications
      for genetic mapping strategies in both human populations and mouse crosses.

PMID- 15489520
TI  - Mutation of l7Rn3 shows that Odz4 is required for mouse gastrulation.
AB  - A mouse homolog of the Drosophila pair-rule gene Odd Oz (Odz4) maps to the
      critical region of the l7Rn3 locus on mouse chromosome 7. Here we show that Odz4
      is an excellent candidate for this allelic series because (1) it spans the entire
      critical region, (2) the phenotypes correlate with embryonic expression, (3) the
      complex genetic inheritance of the alleles is consistent with complex
      transcriptional regulation, and (4) one allele has a mutation in a conserved
      amino acid. Odz4 uses five alternate promoters that encode both secreted and
      membrane-bound proteins. Intragenic complementation of the l7Rn3 alleles is
      consistent with these multiple-protein isoforms. Further, the allelic series
      shows that Odz4 is required to establish the anterior-posterior axis of the
      gastrulating mouse embryo and is necessary later for mesoderm-derived tissues
      such as somites, heart, and skeleton. Sequencing of RT-PCR products from five of
      the six alleles reveals a nonconservative amino acid change in the l7Rn3(m4)
      allele. This amino acid is important evolutionarily, as it is conserved to
      Drosophila. Together, our data indicate that Odz4 is mutated in the l7Rn3 allele
      series and performs roles in the mouse brain, heart, and embryonic patterning
      similar to those of its Drosophila counterpart.

PMID- 15489521
TI  - Nucleotide polymorphism and linkage disequilibrium within and among natural
      populations of European aspen (Populus tremula L., Salicaceae).
AB  - Populus is an important model organism in forest biology, but levels of
      nucleotide polymorphisms and linkage disequilibrium have never been investigated
      in natural populations. Here I present a study on levels of nucleotide
      polymorphism, haplotype structure, and population subdivision in five nuclear
      genes in the European aspen Populus tremula. Results show substantial levels of
      genetic variation. Levels of silent site polymorphisms, pi(s), averaged 0.016
      across the five genes. Linkage disequilibrium was generally low, extending only a
      few hundred base pairs, suggesting that rates of recombination are high in this
      obligate outcrossing species. Significant genetic differentiation was found at
      all five genes, with an average estimate of F(ST) = 0.116. Levels of polymorphism
      in P. tremula are 2- to 10-fold higher than those in other woody, long-lived
      perennial plants, such as Pinus and Cryptomeria. The high levels of nucleotide
      polymorphism and low linkage disequilibrium suggest that it may be possible to
      map functional variation to very fine scales in P. tremula using association
      mapping approaches.

PMID- 15489522
TI  - A genetic linkage map of the mimetic butterfly Heliconius melpomene.
AB  - Heliconius melpomene is a mimetic butterfly that exhibits great geographic
      variation in color pattern. We present here a genetic linkage map based on
      analysis of genetic markers in 73 individuals from a single F(2) family,
      offspring of a cross between H. m. cythera from western Ecuador and H. m.
      melpomene from French Guiana. A novel "three-step method" is described for the
      analysis of dominant markers in an F(2) cross, using outbred parental strains and
      taking advantage of the lack of crossing over in female Lepidoptera. This method
      is likely to prove useful for future mapping studies in outbred species with
      crossing over restricted to one sex, such as the Lepidoptera and Drosophila. The
      resulting linkage map has 21 linkage groups corresponding to the 21 chromosomes
      of H. melpomene and includes 219 AFLP markers, 23 microsatellites, 19 single-copy
      nuclear genes, and the color pattern switch genes Yb and Sb. The marker density
      is high, averaging >1/7 cM. The total map length is 1616 cM and the average
      chromosome length is 77 cM. The genome size of H. melpomene was estimated to be
      292 Mb, giving a relationship of physical-to-map distance of 180 kb/cM. This map
      forms the basis for future comparative linkage analysis of color pattern
      evolution in Heliconius.

PMID- 15489523
TI  - Structure and evolution of the r/b chromosomal regions in rice, maize and
      sorghum.
AB  - The r1 and b1 genes of maize, each derived from the chromosomes of two
      progenitors that hybridized >4.8 million years ago (MYA), have been a rich source
      for studying transposition, recombination, genomic imprinting, and paramutation.
      To provide a phylogenetic context to the genetic studies, we sequenced
      orthologous regions from maize and sorghum (>600 kb) surrounding these genes and
      compared them with the rice genome. This comparison showed that the homologous
      regions underwent complete or partial gene deletions, selective retention of
      orthologous genes, and insertion of nonorthologous genes. Phylogenetic analyses
      of the r/b genes revealed that the ancestral gene was amplified independently in
      different grass lineages, that rice experienced an intragenomic gene movement and
      parallel duplication, that the maize r1 and b1 genes are descendants of two
      divergent progenitors, and that the two paralogous r genes of sorghum are almost
      as old as the sorghum lineage. Such sequence mobility also extends to linked
      genes. The cisZOG genes are characterized by gene amplification in an ancestral
      grass, parallel duplications and deletions in different grass lineages, and
      movement to a nonorthologous position in maize. In addition to gene mobility,
      both maize and rice regions experienced recent transposition (<3 MYA).

PMID- 15489524
TI  - How the Rgt1 transcription factor of Saccharomyces cerevisiae is regulated by
      glucose.
AB  - Rgt1 is a transcription factor that regulates expression of HXT genes encoding
      glucose transporters in the yeast Saccharomyces cerevisiae. Rgt1 represses HXT
      gene expression in the absence of glucose; high levels of glucose cause Rgt1 to
      activate expression of HXT1. We identified four functional domains of Rgt1. A
      domain required for transcriptional repression (amino acids 210-250) is required
      for interaction of Rgt1 with the Ssn6 corepressor. Another region of Rgt1 (320
      380) is required for normal transcriptional activation, and sequences flanking
      this region (310-320 and 400-410) regulate this function. A central region (520
      830) and a short sequence adjacent to the zinc cluster DNA-binding domain (80-90)
      inhibit transcriptional repression when glucose is present. We found that this
      middle region of Rgt1 physically interacts with the N-terminal portion of the
      protein that includes the DNA-binding domain. This interaction is inhibited by
      the Rgt1 regulator Mth1, which binds to Rgt1. Our results suggest that Mth1
      promotes transcriptional repression by Rgt1 by binding to it and preventing the
      intramolecular interaction, probably by preventing phosphorylation of Rgt1,
      thereby enabling Rgt1 to bind to DNA. Glucose induces HXT1 gene expression by
      causing Mth1 degradation, allowing Rgt1 phosphorylation, and leading to the
      intramolecular interaction that inhibits DNA binding of Rgt1.

PMID- 15489525
TI  - Functional evolution of the vertebrate Myb gene family: B-Myb, but neither A-Myb
      nor c-Myb, complements Drosophila Myb in hemocytes.
AB  - The duplication of genes and genomes is believed to be a major force in the
      evolution of eukaryotic organisms. However, different models have been presented
      about how duplicated genes are preserved from elimination by purifying selection.
      Preservation of one of the gene copies due to rare mutational events that result
      in a new gene function (neofunctionalization) necessitates that the other gene
      copy retain its ancestral function. Alternatively, preservation of both gene
      copies due to rapid divergence of coding and noncoding regions such that neither
      retains the complete function of the ancestral gene (subfunctionalization) may
      result in a requirement for both gene copies for organismal survival. The
      duplication and divergence of the tandemly arrayed homeotic clusters have been
      studied in considerable detail and have provided evidence in support of the
      subfunctionalization model. However, the vast majority of duplicated genes are
      not clustered tandemly, but instead are dispersed in syntenic regions on
      different chromosomes, most likely as a result of genome-wide duplications and
      rearrangements. The Myb oncogene family provides an interesting opportunity to
      study a dispersed multigene family because invertebrates possess a single Myb
      gene, whereas all vertebrate genomes examined thus far contain three different
      Myb genes (A-Myb, B-Myb, and c-Myb). A-Myb and c-Myb appear to have arisen by a
      second round of gene duplication, which was preceded by the acquisition of a
      transcriptional activation domain in the ancestral A-Myb/c-Myb gene generated
      from the initial duplication of an ancestral B-Myb-like gene. B-Myb appears to be
      essential in all dividing cells, whereas A-Myb and c-Myb display tissue-specific
      requirements during spermatogenesis and hematopoiesis, respectively. We now
      report that the absence of Drosophila Myb (Dm-Myb) causes a failure of larval
      hemocyte proliferation and lymph gland development, while Dm-Myb(-/-) hemocytes
      from mosaic larvae reveal a phagocytosis defect. In addition, we show that
      vertebrate B-Myb, but neither vertebrate A-Myb nor c-Myb, can complement these
      hemocyte proliferation defects in Drosophila. Indeed, vertebrate A-Myb and c-Myb
      cause lethality in the presence or absence of endogenous Dm-Myb. These results
      are consistent with a neomorphic origin of an ancestral A-Myb/c-Myb gene from a
      duplicated B-Myb-like gene. In addition, our results suggest that B-Myb and Dm
      Myb share essential conserved functions that are required for cell proliferation.
      Finally, these experiments demonstrate the utility of genetic complementation in
      Drosophila to explore the functional evolution of duplicated genes in
      vertebrates.

PMID- 15489526
TI  - The meiotic recombination hot spot ura4A in Schizosaccharomyces pombe.
AB  - The meiotic recombination hot spot ura4A (formerly ura4-aim) of
      Schizosaccharomyces pombe was observed at the insertion of the ura4+ gene 15 kb
      centromere-proximal to ade6 on chromosome III. Crosses heterozygous for the
      insertion showed frequent conversion at the heterology with preferential loss of
      the insertion. This report concerns the characterization of 12 spontaneous ura4A
      mutants. A gradient of conversion ranging from 18% at the 5' end to 6% at the 3'
      end was detected. A novel phenomenon also was discovered: a mating-type-related
      bias of conversion. The allele entering with the h+ parent acts preferentially as
      the acceptor for conversion (ratio of 3:2). Tetrad analysis of two-factor crosses
      showed that heteroduplex DNA is predominantly asymmetrical, enters from the 5'
      end, and more often than not covers the entire gene. Restoration repair of
      markers at the 5' end was inferred. Random spore analyses of two-factor crosses
      and normalization of prototroph-recombinant frequencies to physical distance led
      to the demonstration of map expansion: Crosses involving distant markers yielded
      recombinant frequencies higher than the sum of the frequencies measured in the
      subintervals. Finally, marker effects on recombination were defined for two of
      the ura4A mutations.

PMID- 15489527
TI  - Photoperiod regulates flower meristem development in Arabidopsis thaliana.
AB  - Photoperiod has been known to regulate flowering time in many plant species. In
      Arabidopsis, genes in the long day (LD) pathway detect photoperiod and promote
      flowering under LD. It was previously reported that clavata2 (clv2) mutants grown
      under short day (SD) conditions showed suppression of the flower meristem
      defects, namely the accumulation of stem cells and the resulting production of
      extra floral organs. Detailed analysis of this phenomenon presented here
      demonstrates that the suppression is a true photoperiodic response mediated by
      the inactivation of the LD pathway under SD. Inactivation of the LD pathway was
      sufficient to suppress the clv2 defects under LD, and activation of the LD
      pathway under SD conditions restored clv2 phenotypes. These results reveal a
      novel role of photoperiod in flower meristem development in Arabidopsis. Flower
      meristem defects of clv1 and clv3 mutants are also suppressed under SD, and
      35S:CO enhanced the defects of clv3, indicating that the LD pathway works
      independently from the CLV genes. A model is proposed to explain the interactions
      between photoperiod and the CLV genes.

PMID- 15489528
TI  - A mutation with major effects on Drosophila melanogaster sex pheromones.
AB  - Sex pheromones are intraspecific chemical signals that are crucial for mate
      attraction and discrimination. In Drosophila melanogaster, the predominant
      hydrocarbons on the cuticle of mature female and male flies are radically
      different and tend to stimulate or inhibit male courtship, respectively. This
      sexual difference depends largely upon the number of double bonds (one in males
      and two in females) added by desaturase enzymes. A mutation was caused by a PGal4
      transposon inserted in the desat1 gene that codes for the desaturase crucial for
      setting these double bonds. Homozygous mutant flies produced 70-90% fewer sex
      pheromones than control flies, and the pheromonal difference between the sexes
      was almost abolished. A total of 134 excision alleles were induced by pulling out
      all or a part of the transposon. The pheromonal profile was generally rescued in
      excision alleles with a completely or largely removed transposon whereas it
      remained mutant in alleles with a larger piece of the transposon. Five desat1
      transcripts were detected during larval-to-adult development. Their levels were
      precisely quantified in 24-hr-old adults, a critical period for the production of
      sex pheromones. Three transcripts significantly varied between control females
      and males; however, the predominant transcript showed no difference. In mutant
      flies, the predominant transcript was highly decreased with the two sexually
      dimorphic transcripts. These two transcripts were also absent in the sibling
      species D. simulans, which shows no sexually dimorphic hydrocarbons. We also
      induced a larval-lethal allele that lacked all transcripts and failed to
      complement the defective hydrocarbon phenotype of mutant alleles.

PMID- 15489529
TI  - Nonadditive gene expression in diploid and triploid hybrids of maize.
AB  - The molecular basis of hybrid vigor (heterosis) has remained unknown despite the
      importance of this phenomenon in evolution and in practical breeding programs. To
      formulate a molecular basis of heterosis, an understanding of gene expression in
      inbred and hybrid states is needed. In this study, we examined the amount of
      various transcripts in hybrid and inbred individuals (B73 and Mo17) to determine
      whether the quantities of specific messenger RNAs were additive or nonadditive in
      the hybrids. Further, we examined the levels of the same transcripts in hybrid
      triploid individuals that had received unequal genomic contributions, one haploid
      genome from one parent and two from the other. If allelic expression were merely
      the additive value in hybrids from the two parents, the midparent values would be
      observed. Our study revealed that a substantial number of genes do not exhibit
      the midparent value of expression in hybrids. Instead, transcript levels in the
      diploid hybrids correlate negatively with the levels in diploid inbreds. Although
      transcript levels were clearly nonadditive, transcript levels in triploid hybrids
      were affected by genomic dosage.

PMID- 15489530
TI  - Variation after a selective sweep in a subdivided population.
AB  - The effect of genetic hitchhiking on neutral variation is analyzed in subdivided
      populations with differentiated demes. After fixation of a favorable mutation,
      the consequences on particular subpopulations can be radically different. In the
      subpopulation where the mutation first appeared by mutation, variation at linked
      neutral loci is expected to be reduced, as predicted by the classical theory.
      However, the effect in the other subpopulations, where the mutation is introduced
      by migration, can be the opposite. This effect depends on the level of genetic
      differentiation of the subpopulations, the selective advantage of the mutation,
      the recombination frequency, and the population size, as stated by analytical
      derivations and computer simulations. The characteristic outcomes of the effect
      are three. First, the genomic region of reduced variation around the selected
      locus is smaller than that predicted in a panmictic population. Second, for more
      distant neutral loci, the amount of variation increases over the level they had
      before the hitchhiking event. Third, for these loci, the spectrum of gene
      frequencies is dominated by an excess of alleles at intermediate frequencies when
      compared with the neutral theory. At these loci, hitchhiking works like a system
      that takes variation from the between-subpopulation component and introduces it
      into the subpopulations. The mechanism can also operate in other systems in which
      the genetic variation is distributed in clusters with limited exchange of
      variation, such as chromosome arrangements or genomic regions closely linked to
      targets of balancing selection.

PMID- 15489531
TI  - Characterization of AFLP sequences from regions of maize B chromosome defined by
      12 B-10L translocations.
AB  - Maize B chromosome sequences have been previously cloned by microdissection, and
      all are proven to be highly repetitive, to be homologous to the normal
      complement, and to show no similarity to any published gene other than mobile
      elements. In this study, we isolated sequences from defined B regions. The
      strategy involved identification and then mapping of AFLP-derived B fragments
      before cloning. Of 14 B AFLPs, 13 were mapped by 12 B-10L translocations: 3
      around the centromeric knob region, 3 in the proximal euchromatic, 1 around the
      border of proximal euchromatic and distal heterochromatic, and 6 in the distal
      heterochromatic region of the B long arm. The AFLP fragments were cloned and
      sequenced. Analogous to the microdissected sequences, all sequences were
      repetitive, and all but two were highly homologous to the A chromosomes. FISH
      signals of all but three clones appeared in pachytene B as well as in somatic A
      and B chromosomes. None of these clones exhibits identity to any published gene.
      Six clones displayed homology to two centromeric BACs, four to sequences of
      chromosomes 3, 4, 7, and 10, four to retrotransposons, and three to no sequence
      deposited in GenBank. Furthermore, flanking regions of two highly B-specific
      clones were characterized, showing extension of a B-exclusive nature. The
      possibility of the presence of novel B repeat(s) is discussed.

PMID- 15489532
TI  - Suppression of histone H1 genes in Arabidopsis results in heritable developmental
      defects and stochastic changes in DNA methylation.
AB  - Histone H1 is an abundant component of eukaryotic chromatin that is thought to
      stabilize higher-order chromatin structures. However, the complete knock-out of
      H1 genes in several lower eukaryotes has no discernible effect on their
      appearance or viability. In higher eukaryotes, the presence of many mutually
      compensating isoforms of this protein has made assessment of the global function
      of H1 more difficult. We have used double-stranded RNA (dsRNA) silencing to
      suppress all the H1 genes of Arabidopsis thaliana. Plants with a >90% reduction
      in H1 expression exhibited a spectrum of aberrant developmental phenotypes, some
      of them resembling those observed in DNA hypomethylation mutants. In subsequent
      generations these defects segregated independently of the anti-H1 dsRNA
      construct. Downregulation of H1 genes did not cause substantial genome-wide DNA
      hypo- or hypermethylation. However, it was correlated with minor but
      statistically significant changes in the methylation patterns of repetitive and
      single-copy sequences, occurring in a stochastic manner. These findings reveal an
      important and previously unrecognized link between linker histones and specific
      patterns of DNA methylation.

PMID- 15489533
TI  - The Dlx gene complement of the leopard shark, Triakis semifasciata, resembles
      that of mammals: implications for genomic and morphological evolution of jawed
      vertebrates.
AB  - Extensive gene duplication is thought to have occurred in the vertebrate lineage
      after it diverged from cephalochordates and before the divergence of lobe- and
      ray-finned fishes, but the exact timing remains obscure. This timing was
      investigated by analysis of the Dlx gene family of a representative cartilaginous
      fish, the leopard shark, Triakis semifasciata. Dlx genes encode homeodomain
      transcription factors and are arranged in mammals as three convergently
      transcribed bigene clusters. Six Dlx genes were cloned from Triakis and shown to
      be orthologous to single mammalian Dlx genes. At least four of these are arranged
      in bigene clusters. Phylogenetic analyses of Dlx genes were used to propose an
      evolutionary scenario in which two genome duplications led to four Dlx bigene
      clusters in a common ancestor of jawed vertebrates, one of which was lost prior
      to the diversification of the group. Dlx genes are known to be involved in jaw
      development, and changes in Dlx gene number are mapped to the same branch of the
      vertebrate tree as the origin of jaws.

PMID- 15489534
TI  - Coalescent-based association mapping and fine mapping of complex trait loci.
AB  - We outline a general coalescent framework for using genotype data in linkage
      disequilibrium-based mapping studies. Our approach unifies two main goals of gene
      mapping that have generally been treated separately in the past: detecting
      association (i.e., significance testing) and estimating the location of the
      causative variation. To tackle the problem, we separate the inference into two
      stages. First, we use Markov chain Monte Carlo to sample from the posterior
      distribution of coalescent genealogies of all the sampled chromosomes without
      regard to phenotype. Then, averaging across genealogies, we estimate the
      likelihood of the phenotype data under various models for mutation and penetrance
      at an unobserved disease locus. The essential signal that these models look for
      is that in the presence of disease susceptibility variants in a region, there is
      nonrandom clustering of the chromosomes on the tree according to phenotype. The
      extent of nonrandom clustering is captured by the likelihood and can be used to
      construct significance tests or Bayesian posterior distributions for location. A
      novelty of our framework is that it can naturally accommodate quantitative data.
      We describe applications of the method to simulated data and to data from a
      Mendelian locus (CFTR, responsible for cystic fibrosis) and from a proposed
      complex trait locus (calpain-10, implicated in type 2 diabetes).

PMID- 15489536
TI  - The amplification model for adaptive mutation: simulations and analysis.
AB  - It has been proposed that the lac revertants arising under selective conditions
      in the Cairns experiment do not arise by stress-induced mutagenesis of stationary
      phase cells as has been previously assumed. Instead, these revertants may arise
      within growing clones initiated by cells with a preexisting duplication of the
      weakly functional lac allele used in this experiment. It is proposed that
      spontaneous stepwise increases in lac copy number (amplification) allow a
      progressive improvement in growth. Reversion is made more likely primarily by the
      resultant increase in the number of mutational targets--more cells with more lac
      copies. The gene amplification model requires no stress-induced variation in the
      rate or target specificity of mutation and thus does not violate neo-Darwinian
      theory. However, it does require that a multistep process of amplification,
      reversion, and amplification segregation be completed within approximately 20
      generations of growth. This work examines the proposed amplification model from a
      theoretical point of view, formalizing it into a mathematical framework and using
      this to determine what would be required for the process to occur within the
      specified period. The analysis assumes no stress-induced change in mutation rate
      and describes only the growth improvement occurring during the process of
      amplification and subsequent elimination of excess mutant lac copies. The
      dynamics of the system are described using Monte Carlo simulations and numerical
      integration of the deterministic equations governing the system. The results
      imply that the amplification model can account for the behavior of the system
      using biologically reasonable parameter values and thus can, in principle,
      explain Cairnsian adaptive mutation.

PMID- 15489537
TI  - The LF1 gene of Chlamydomonas reinhardtii encodes a novel protein required for
      flagellar length control.
AB  - Flagellar length is tightly regulated in the biflagellate alga Chlamydomonas
      reinhardtii. Several genes required for control of flagellar length have been
      identified, including LF1, a gene required to assemble normal-length flagella.
      The lf1 mutation causes cells to assemble extra-long flagella and to regenerate
      flagella very slowly after amputation. Here we describe the positional cloning
      and molecular characterization of the LF1 gene using a bacterial artificial
      chromosome (BAC) library. LF1 encodes a protein of 804 amino acids with no
      obvious sequence homologs in other organisms. The single LF1 mutant allele is
      caused by a transversion that produces an amber stop at codon 87. Rescue of the
      lf1 phenotype upon transformation was obtained with clones containing the
      complete LF1 gene as well as clones that lack the last two exons of the gene,
      indicating that only the amino-terminal portion of the LF1 gene product (LF1p) is
      required for function. Although LF1 helps regulate flagellar length, the LF1p
      localizes almost exclusively in the cell body, with <1% of total cellular LF1p
      localizing to the flagella.

PMID- 15489538
TI  - On the meaning and existence of an effective population size.
AB  - We investigate conditions under which a model with stochastic demography or
      population structure converges to the coalescent with a linear change in
      timescale. We argue that this is a necessary condition for the existence of a
      meaningful effective population size. We find that such a linear timescale change
      is obtained when demographic fluctuations and coalescence events occur on
      different timescales. Simple models of population structure and randomly
      fluctuating population size are used to exemplify the ideas and provide an
      intuitive feel for the meaning of the conditions.

PMID- 15489535
TI  - Genetic diversity, recombination and cryptic clades in Pseudomonas viridiflava
      infecting natural populations of Arabidopsis thaliana.
AB  - Species-level genetic diversity and recombination in bacterial pathogens of wild
      plant populations have been nearly unexplored. Pseudomonas viridiflava is a
      common natural bacterial pathogen of Arabidopsis thaliana, for which pathogen
      defense genes and mechanisms are becoming increasing well known. The genetic
      variation contained within a worldwide sample of P. viridiflava collected from
      wild populations of A. thaliana was investigated using five genomic sequence
      fragments totaling 2.3 kb. Two distinct and deeply diverged clades were found
      within the P. viridiflava sample and in close proximity in multiple populations,
      each genetically diverse with synonymous variation as high as 9.3% in one of
      these clades. Within clades, there is evidence of frequent recombination within
      and between each sequenced locus and little geographic differentiation. Isolates
      from both clades were also found in a small sample of other herbaceous species in
      Midwest populations, indicating a possibly broad host range for P. viridiflava.
      The high levels of genetic variation and recombination together with a lack of
      geographic differentiation in this pathogen distinguish it from other bacterial
      plant pathogens for which intraspecific variation has been examined.

PMID- 15489539
TI  - PPAR- and LXR-dependent pathways controlling lipid metabolism and the development
      of atherosclerosis.
AB  - The nuclear receptor superfamily is composed of transcription factors that
      positively and negatively regulate gene expression in response to the binding of
      a diverse array of lipid-derived hormones and metabolites. Intense efforts are
      currently being directed at defining the biological roles and mechanisms of
      action of liver X receptors (LXRs) and peroxisome proliferator-activated
      receptors (PPARs). LXRs have been found to play essential roles in the regulation
      of whole body cholesterol absorption and excretion, in the efflux of cholesterol
      from peripheral cells, and in the biosynthesis and metabolism of very low density
      lipoproteins. PPARs have been found to regulate diverse aspects of lipid
      metabolism, including fatty acid oxidation, fat cell development, lipoprotein
      metabolism, and glucose homeostasis. Intervention studies indicate that
      activation of PPARalpha, PPARgamma, and LXRs by specific synthetic ligands can
      inhibit the development of atherosclerosis in animal models. Here, we review
      recent studies that provide new insights into the mechanisms by which these
      subclasses of nuclear receptors act to systemically influence lipid and glucose
      metabolism and regulate gene expression within the artery wall.

PMID- 15489540
TI  - Resistin expression in 3T3-L1 adipocytes is reduced by arachidonic acid.
AB  - The resistin gene is expressed in adipocytes and encodes a protein proposed to
      link obesity and type 2 diabetes. Increased plasma FFA is associated with insulin
      resistance. We examined the effect of separate FFAs on the expression of resistin
      mRNA in cultured murine 3T3-L1 adipocytes. The FFAs tested did not increase
      resistin expression, whereas both arachidonic acid (AA) and eicosapentaenoic acid
      (EPA) reduced resistin mRNA levels. AA was by far the most potent FFA, reducing
      resistin mRNA levels to approximately 20% of control at 60-250 muM concentration.
      Selective inhibitors of cyclooxygenase-1 and of mitogen-activated protein kinase
      kinase counteracted AA-induced reduction in resistin mRNA levels. Transient
      overexpression of sterol-regulatory element binding protein-1a (SREBP-1a)
      activated the resistin promoter, but there was no reduction in the abundance of
      approximately 65 kDa mature SREBP-1 after AA exposure. Actinomycin D as well as
      cycloheximide abolished the AA-induced reduction of resistin mRNA levels,
      indicating dependence on de novo transcription and translation. Our data suggest
      that reductions in resistin mRNA levels involve a destabilization of the resistin
      mRNA molecule. An inhibitory effect of AA and EPA on resistin expression may
      explain the beneficial effect of ingesting PUFAs on insulin sensitivity.

PMID- 15489541
TI  - LDL phospholipid hydrolysis produces modified electronegative particles with an
      unfolded apoB-100 protein.
AB  - Electronegative low density lipoprotein (LDL(-)) formation that structurally
      resembles LDL(-) isolated from plasma was evaluated after LDL treatment with
      snake venom phospholipase A(2) (PLA(2)). PLA(2) treatment of LDL increased its
      electrophoretic mobility in proportion to the amount of LDL(-) formed without
      evidence of lipid peroxidation. These changes dose-dependently correlated with
      the degree of phospholipid hydrolysis. Strong immunoreactivity of LDL(-)
      subfraction from plasma and PLA(2)-treated LDL (PLA(2)-LDL) to amyloid oligomer
      specific antibody was observed. Higher beta-strand structural content and
      unfolding proportionate to the loss of alpha-helical structure of apolipoprotein
      B-100 (apoB-100) of LDL(-) isolated from both native and PLA(2)-LDLs was
      demonstrated by circular dichroism (CD) spectropolarimetry. These structural
      changes resembled the characteristics of some oxidatively modified LDLs and
      soluble oligomeric aggregates of amyloidogenic proteins. PLA(2)-LDL was also more
      susceptible to nitration by peroxynitrite, likely because of exposure of
      otherwise inaccessible hydrophilic and hydrophobic domains arising from apoB-100
      unfolding. This was also demonstrated for plasma LDL(-). In contrast, PLA(2)-LDL
      was more resistant to copper-mediated oxidation that was reversed upon the
      addition of small amounts of unsaturated fatty acids. The observed similarities
      between PLA(2)-LDL(-)-derived LDL(-) and plasma LDL(-) implicate a role for
      secretory PLA(2) in producing modified LDL(-) that is facilitated by unfolding of
      apoB-100.

PMID- 15489542
TI  - Characterization of differentiated subcutaneous and visceral adipose tissue from
      children: the influences of TNF-alpha and IGF-I.
AB  - The relationship between subcutaneous and visceral adipocyte metabolism and
      development has been extensively studied in adult but not in pediatric tissue.
      Our aim was to isolate, develop, characterize, and compare primary cell cultures
      of subcutaneous and visceral preadipocytes from 16 normal prepubertal children
      (10 male and 6 female). Subculture techniques were developed to increase cell
      number and allow differentiation using a chemically defined serum-free medium.
      Removal of insulin from the differentiation medium prevented adipogenesis in both
      subcutaneous and visceral preadipocytes, whereas coincubation with rosiglitazone
      markedly enhanced glycerol-3-phosphate dehydrogenase activity, peroxisome
      proliferator-activated receptor gamma expression, and triglyceride accumulation
      in cells from both fat depots. Adiponectin secretion increased with
      differentiation from undetectable levels at day 0. Histological analyses
      demonstrated significant differences in lipid droplet number and size, with
      subcutaneous cells having fewer but larger vesicles compared with visceral cells.
      Downregulation and reorganization of the cytoskeleton appeared comparable. We
      further demonstrate regional differences in adipogenesis manipulation. Tumor
      necrosis factor-alpha was more effective at inhibiting differentiation in
      subcutaneous cells, whereas insulin-like growth factor-I stimulated
      differentiation more effectively in visceral cells. Insulin-like growth factor
      binding protein-3 enhanced differentiation equally. These observations may have
      important physiological and pharmacological implications for the development of
      obesity in later life.

PMID- 15489543
TI  - Selective activation of vitamin D receptor by lithocholic acid acetate, a bile
      acid derivative.
AB  - The vitamin D receptor (VDR), a member of the nuclear receptor superfamily,
      mediates the biological actions of the active form of vitamin D, 1alpha,25
      dihydroxyvitamin D(3). It regulates calcium homeostasis, immunity, cellular
      differentiation, and other physiological processes. Recently, VDR was found to
      respond to bile acids as well as other nuclear receptors, farnesoid X receptor
      (FXR) and pregnane X receptor (PXR). The toxic bile acid lithocholic acid (LCA)
      induces its metabolism through VDR interaction. To elucidate the structure
      function relationship between VDR and bile acids, we examined the effect of
      several LCA derivatives on VDR activation and identified compounds with more
      potent activity than LCA. LCA acetate is the most potent of these VDR agonists.
      It binds directly to VDR and activates the receptor with 30 times the potency of
      LCA and has no or minimal activity on FXR and PXR. LCA acetate effectively
      induced the expression of VDR target genes in intestinal cells. Unlike LCA, LCA
      acetate inhibited the proliferation of human monoblastic leukemia cells and
      induced their monocytic differentiation. We propose a docking model for LCA
      acetate binding to VDR. The development of VDR agonists derived from bile acids
      should be useful to elucidate ligand-selective VDR functions.

PMID- 15489544
TI  - A new combined multicompartmental model for apolipoprotein B-100 and triglyceride
      metabolism in VLDL subfractions.
AB  - The use of stable isotopes in conjunction with compartmental modeling analysis
      has greatly facilitated studies of the metabolism of the apolipoprotein B (apoB)
      containing lipoproteins in humans. The aim of this study was to develop a
      multicompartment model that allows us to simultaneously determine the kinetics of
      apoB and triglyceride (TG) in VLDL(1) and VLDL(2) after a bolus injection of
      [(2)H(3)]leucine and [(2)H(5)]glycerol and to follow the catabolism and transfer
      of the lipoprotein particles. Here, we describe the model and present the results
      of its application in a fasting steady-state situation in 17 subjects with lipid
      values representative of a Western population. Analysis of the correlations
      showed that plasma TG was determined by the VLDL(1) and VLDL(2) apoB and TG
      fractional catabolic rate. Furthermore, the model showed a linear correlation
      between VLDL(1) TG and apoB production. A novel observation was that VLDL TG
      entered the circulation within 21 min after its synthesis, whereas VLDL apoB
      entered the circulation after 33 min. These observations are consistent with a
      sequential assembly model of VLDL and suggest that the TG is added to a
      primordial apoB-containing particle in the liver.

PMID- 15489545
TI  - Characterization and direct quantitation of cerebroside molecular species from
      lipid extracts by shotgun lipidomics.
AB  - By using shotgun lipidomics based on the separation of lipid classes in the
      electrospray ion source (intrasource separation) and two-dimensional (2D) MS
      techniques (Han, X., and R. W. Gross. 2004. Shotgun lipidomics: electrospray
      ionization mass spectrometric analysis and quantitation of the cellular lipidomes
      directly from crude extracts of biological samples. Mass Spectrom. Rev. First
      published on June 18, 2004; doi: 10.1002/mas.20023, In press), individual
      molecular species of most major and many minor lipid classes can be quantitated
      directly from biological lipid extracts. Herein, we extended shotgun lipidomics
      to the characterization and quantitation of cerebroside molecular species in
      biological samples. By exploiting the differential fragmentation patterns of
      chlorine adducts using electrospray ionization (ESI) tandem mass spectrometry,
      hydroxy and nonhydroxy cerebroside species are readily identified. The hexose
      (either galactose or glucose) moiety of a cerebroside species can be
      distinguished by examination of the peak intensity ratio of its product ions at
      m/z 179 and 89 (i.e., 0.74 +/- 0.10 and 4.8 +/- 0.7 for galactose- and glucose
      containing cerebroside species, respectively). Quantitation of cerebroside
      molecular species (as little as 10 fmol) from chloroform extracts of brain tissue
      samples was directly conducted by 2D ESI/MS after correction for differences in
      (13)C-isotopomer intensities. This method was demonstrated to have a greater than
      1,000-fold linear dynamic range in the low concentration region; therefore, it
      should have a wide range of applications in studies of the cellular sphingolipid
      lipidome.

PMID- 15489546
TI  - Rapid quantification of free and esterified phytosterols in human serum using
      APPI-LC-MS/MS.
AB  - A novel analytical platform based on liquid chromatography and tandem mass
      spectrometry using atmospheric pressure photoionization was applied for the
      simultaneous quantification of free and esterified beta-sitosterol, campesterol,
      brassicasterol, and stigmasterol. The total time for sample pretreatment and
      analysis could be reduced from approximately 3 h [gas chromatography-mass
      spectrometry (GC-MS)] to 15 min. The detection limits of the different
      phytosterols ranged between 0.25 and 0.68 microg/l. Linear ranges were between 1
      and 1,000 microg/l. The within-run and between-run variabilities ranged between
      1.4% and 9.9%. The analytical sensitivity was at least 150-fold higher compared
      with GC-MS. Our new method allows a rapid and simultaneous determination of free
      and esterified phytosterols in serum.

PMID- 15489547
TI  - Women's health biobank in India.

PMID- 15489548
TI  - 'Polar Spectrum' of problems in polio eradication.

PMID- 15489549
TI  - Leptospirosis--a reemerging disease?

PMID- 15489550
TI  - Thyroid binding globulin deficiency.

PMID- 15489551
TI  - Neonatal & maternal group B streptococcal infections: a comprehensive review.
AB  - Group B Streptococcus is an important cause of maternal and neonatal morbidity
      and mortality in many parts of the world. The last two decades have seen
      intensified efforts in the Western hemisphere in the prevention of this
      devastating infection by identifying and treating pregnant women who carry group
      B streptococci or who are at highest risk of transmitting the organism to
      newborns. The intrapartum use of antibiotics in these women has led unequivocally
      to a decrease in the rate of neonatal group B streptococcal disease. Although
      studies in India show a predominance of Gram negative bacterial sepsis among
      infants, contributing to infant mortality, it is possible that the role of group
      B Streptococcus has been underestimated. This review discusses its epidemiology
      in India, and summarizes current concepts of microbiology, pathogenesis, clinical
      management and preventative issues regarding group B streptococcal disease.

PMID- 15489552
TI  - Leptospiral proteins expressed during acute & convalescent phases of human
      leptospirosis.
AB  - BACKGROUND & OBJECTIVES: The available serological techniques for the diagnosis
      of leptospirosis have less sensitivity during the early stage of the disease.
      Understanding of leptospiral proteins expressed during acute and convalescent
      phases of leptospirosis, would be help the develop of new serodiagnostic
      strategies. Therefore, the present study was carried out to identify (i) an
      antigen that is conserved among the various pathogenic leptospira; (ii) best
      protein antigen to which immune response can be identified in the acute phase;
      and (iii) best protein antigen which is present in convalescent sera which can be
      used for seroepidemiological studies. METHODS: Quantitative immunoblot analysis
      was performed using acute and convalescent phase human sera along with sera from
      normal healthy individuals and from patients with typhoid, malaria and hepatitis
      as the controls. All the samples were analyzed for the leptospiral protein
      recognition by using IgM and IgG immunoblots. Leptospiral cell fractionation was
      performed using triton X-114 and lysozyme and further the conservation of
      leptospiral proteins was also performed. RESULTS: In confirmed cases of
      leptospirosis, the IgG recognition in acute phase sera was 30.2, 39.5, 27.9, 55.8
      and 27.9 per cent for the leptospiral proteins p32, p41/42, p58, p62 and p82
      respectively. The IgG has considerably increased to 65.1, 55.8, 46.5, 67.4 and
      48.8 per cent against the same proteins during convalescent phase. The IgM
      recognition was 32.6 , 32.6, 30.2 and 37.2 per cent for acute phase sera and
      32.6, 37.2, 44.2 and 41.9 per cent for convalescent phase sera for the
      leptospiral proteins p14, p25, p32 and p41/42, respectively. Leptospiral proteins
      like p62 and p82 were recognized among all the control groups with 3.3-15.3 per
      cent for IgG recognition. INTERPRETATION & CONCLUSION: Leptospiral protein p32
      was found to be highly sensitive and specific and could be useful for the
      development of newer techniques for diagnosis and seroepidemiological studies.
      Combination of p32 and p41/42 for IgG and p14, p25, p32, p41/42 for IgM would
      increase the sensitivity of these techniques further.

PMID- 15489553
TI  - Thyroid hormone binding protein abnormalities in patients referred for thyroid
      disorders.
AB  - BACKGROUND & OBJECTIVES: Thyroid hormone binding protein (THBP) abnormalities are
      the major cause of discordance in commonly performed total thyroxine (T4) and
      thyrotropin (TSH) estimations, though these do not interfere with thyroid hormone
      action. Determination of such abnormalities in patients showing discordant
      thyroid function tests (TFTs) is diagnostically important as it eliminates
      equivocal assessment of thyroid function and treatment especially where proper
      methodology for free T4 (FT4) estimation is not available. This study was
      undertaken to analyse the THBP abnormalities in the population attending thyroid
      clinic. Family members of affected patients were also screened to study the
      inheritance of quantitative TBG abnormalities. METHODS: Blood samples of 15000
      consecutive patients over a period of 4 years (1994-1997) were tested for thyroid
      function. THBP abnormalities were studied using polyacrylamide gel
      electrophoresis autoradiography. Serum thyroxine binding globulin (TBG), free and
      total T4, total tri-iodothyronine (TT3) were assayed by radioimmunoassay methods.
      RESULTS: In our screening of 15,000 thyroid patients over a four year period, we
      found the presence of complete and partial TBG deficiency and TBG excess to be
      1:2,500, 1:200 and 1:15,000 respectively. Our study on the families of three
      affected patients revealed X-chromosome linked inheritance pattern of TBG
      deficiency in two families and TBG excess in one family. INTERPRETATION &
      CONCLUSION: Our study suggests that it would be beneficial to rule out THBP
      abnormalities before interpreting results of TFTs, particularly when there is
      large discrepancy between T4 and TSH levels. In case of inherited THBP
      abnormalities, the family members of the affected individual should also be
      screened to avoid misdiagnosis and erroneous treatment in case they develop
      thyroid dysfunction in future.

PMID- 15489554
TI  - Epidemiological, clinical & pharmacological study of antimony-resistant visceral
      leishmaniasis in Bihar, India.
AB  - BACKGROUND & OBJECTIVES: Sodium antimony gluconate (SAG) is reported to be losing
      its efficacy in Bihar as a first line drug for treatment of visceral
      leishmaniasis (VL). Concerned with the increasing incidence of antimony-resistant
      VL patients in Bihar, we undertook an epidemiological, clinical and
      pharmacological study to formulate a scientific basis for choosing a suitable
      first line drug for VL. METHODS: Consecutive, fresh and parasitologically
      confirmed patients of VL from different geographical areas of Bihar were
      considered for inclusion in the study. Parasites isolated from patients were
      tested in vitro to assess their response to sodium antimony gluconate (SAG) to 20
      microg/ml, response to 20 mg/kg of SAG for 5 days in experimentally induced VL in
      BALB/c mice from those isolates, and response to SAG in patients treated with SAG
      for 28 days. Similarly response in culture (1 microg/ml) to amphotericin B (AMB)
      of all 282 isolates, (1 mg/kg body wt for 20 days) in patients and infected
      BALB/c mice (1 mg/kg body wt for 5 days) was determined. Antimony levels of
      plasma were determined at 2, 8 and 24 h after intramuscular injection of SAG.
      Patients unwilling for SAG treatment or relapsed after SAG treatment and
      withdrawn from SAG group because of toxicity were treated with AMB. Plasma
      antimony levels were estimated by atomic absorption spectrometer. RESULTS: Though
      antimony sensitive and resistant patient were distributed in all 14 districts of
      Bihar studied, there was a significant variation from district to district. Of
      the 123 patients included in the SAG treatment group, 19 were withdrawn due to
      development of toxicity and 2 died; 178 patients were treated with AMB. No
      patient in AMB group developed any toxicity or died. Only 47 (46%) of 102
      patients, 106 (37.6%) of 282 infected macrophages, 90 (52.9%) of 170 experimental
      infections were cured with SAG. Mc Nemar's test on paired comparisons showed
      statistical significance difference (P<0.01) between infected macrophage and
      experimental infection. AMB cured all patients, infected mice and cleared
      parasites from all isolates. INTERPRETATION & CONCLUSION: Antimony resistant
      strains of L. donovani were wide spread over different geographical areas in
      Bihar. SAG cured lesser percentage of VL cases clinically compared to AMB and
      should be replaced by AMB as a first line drug.

PMID- 15489555
TI  - A preliminary study of multilevel geographic distribution & prevalence of Aedes
      aegypti (Diptera: Culicidae) in the state of Goa, India.
AB  - BACKGROUND & OBJECTIVES: Dengue virus activity has never been reported in the
      state of Goa. The present study was carried out to document a multilevel
      geographic distribution, prevalence and preliminary analysis of risk factors for
      the invasions of Aedes aegypti in Goa. METHODS: A geographic information system
      (GIS) based Ae. aegypti surveys were conducted in dry (April 2002) and wet (July
      2002) seasons in the rural and urban settlements. The random walk method was used
      for household coverage. The non-residential area visits included ancillaries of
      roadways, railways, air-and seaports. Simultaneous adult mosquito collections and
      one-larva per container technique were adopted. RESULTS: The Ae. aegypti larval
      and adult prevalence was noted in all the four urban areas in both dry (Density
      index (DI)= 3 to 6) and wet (DI= 5 to 7) seasons and only one out of 3 villages
      showed Ae aegypti presence in wet season (DI= 5 to 7). In the residential areas,
      hutments showed higher relative prevalence indices (Breteau index, BI=100;
      container index, CI=11.95; adult house index, AHI=13.33) followed by close set
      cement houses (BI=44.1; CI=12.0; AHI=11.24). Ae aegypti relative prevalence
      indices were also more for households with pets (BI=85.11; CI=12.5; AHI= 42.85);
      those with tap had higher risk (larval house index, LHI =32.03; relative risk,
      RR>2, n=256). Plastic drum was the most preferred breeding place (chi(2) = 19.81;
      P<0.01; RR=3.41) among domestic containers and rubber tyres (chi(2) = 11.86;
      P<0.01; RR=3.61)among sundry/rainfilled containers. INTERPRETATION & CONCLUSION:
      Established Ae aegypti prevalence in the urban settlements during dry and wet
      seasons and its scattered distribution in a rural settlement spell risk of dengue
      infection at macro-level. In the residential areas nature and types of the
      households, tap water supply and storage and communities' attitude and practices
      contribute to sustained meso-level risk of Ae aegypti prevalence dependant DEN.
      The non-residential areas offer transient meso-level risk as Ae aegypti
      prevalence was seasonally unstable and monsoon dependent. Risk at micro-level was
      due to the preferred larval habitats of Ae aegypti breeding viz., residential
      plastic-ware and tyres, and transport tyres in non-residential areas.

PMID- 15489556
TI  - Efficacy & tolerability of ondansetron compared to metoclopramide in dose
      dependent cisplatin-induced delayed emesis.
AB  - BACKGROUND & OBJECTIVES: Delayed emesis with cisplatin is a significant problem,
      which is often poorly controlled with conventional antiemetics. There is a
      relative paucity of data on the control of delayed emesis and rather inconsistent
      results have been reported. The present study aimed to compare the efficacy and
      tolerability of ondansetron versus metoclopramide in dose related grades of
      cisplatin-induced delayed emesis. METHODS: A total of 80 chemotherapy naive
      patients with malignancy were randomized to receive cisplatin 60 mg/m2
      intravenously (iv) either as a single dose on day 1 (high dose regimen) or split
      into three doses of 20 mg/m2 each on 3 days (low dose regimen) along with
      bleomycin +5- fluorouracil in 40 patients each. Patients were further randomized
      in each cisplatin regimen to receive either 20 mg metoclopramide (20 patients) or
      8 mg ondansetron (20 patients) iv 30 min prior to cisplatin administration
      followed by the respective antiemetic orally 8 hourly for five days after the
      last cisplatin administration. Ten patients receiving high dose cisplatin in each
      group were also given dexamethasone 8 mg iv with the primary antiemetic. The
      assessment period started 24 h after last cisplatin infusion and ended at
      midnight on day 5. RESULTS: In low dose cisplatin regimen, complete suppression
      of delayed emesis occurred in 55 per cent patients receiving ondansetron and in
      30 per cent patients receiving metoclopramide. Neither ondansetron nor
      metoclopramide could completely suppress delayed emesis in high dose cisplatin
      regimen. Protection from nausea in the delayed phase was seen in 85 per cent
      patients receiving ondansetron and in 70 per cent patients receiving
      metoclopramide in low dose regimen, while nausea protection rates were 70 vs 0
      per cent respectively in the high dose regimen. Addition of dexamethasone to
      metoclopramide significantly augmented its antiemetic efficacy (P<0.02) and the
      combination of metoclopramide + dexamethasone was found to be as efficacious as
      ondansetron monotherapy. Twenty out of 80 patients reported 39 adverse events of
      mild intensity. No significant effects on QOL (quality of life) parameters were
      observed in any group over the 5-day period. INTERPRETATION & CONCLUSION: The
      results demonstrate that delayed emesis due to cisplatin is also dose related,
      and superior antiemetic efficacy of ondansetron compared to metoclopramide is
      maintained, though its superiority is less marked than against acute emesis.
      Metoclopramide and dexamethasone combination matched the antiemetic efficacy of
      ondansetron monotherapy.

PMID- 15489557
TI  - Effect of Solanum trilobatum against carbon tetrachloride induced hepatic damage
      in albino rats.
AB  - BACKGROUND & OBJECTIVES: Many hepatoprotective herbal preparations have been
      recommended in alternative systems of medicine for the treatment of hepatic
      disorders. No systematic study has been done on protective efficacy of Solanum
      trilobatum to treat hepatic diseases. Protective action of Solanum trilobatum
      extract (STE) was evaluated by us in an animal model of hepatotoxicity induced by
      carbon tetrachloride (CCl4). METHODS: Wistar albino rats were divided into five
      groups. Group I was normal control group; Group II, the hepatotoxic group was
      given CCl4; Groups III-V received different doses of plant extract with CCl(4).
      Liver marker enzymes were assayed in serum and antioxidant status was assessed in
      liver tissue. RESULTS: Levels of marker enzymes such as alanine transminase
      (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and lactate
      dehydrogenase (LDH) were increased significantly in CCl4 treated rats (group II).
      STE brought about a significant decrease in the activities of all these enzymes.
      Lipid peroxidation (LP) was increased significant in liver tissue in the CCl4
      treated rats (group II) while the activities of glutathione peroxidase (GPx),
      catalase (CAT) and superoxide dismutase (SOD) were decreased. STE treatment led
      to the recovery of these levels to near normal. INTERPRETATION & CONCLUSION: The
      present observations suggested that the treatment with S. trilobatum extract
      enhance the recovery from CCl4 induced hepatic damage due to its antioxidant and
      hepatoprotective property.

PMID- 15489558
TI  - Prevalence of group G & group C streptococci at an Indian tertiary care centre.

PMID- 15489559
TI  - The burden of anaemia in patients with cancer.
AB  - Anaemia is highly prevalent in patients with cancer, and its incidence and
      severity depend on many factors, such as type of anti-cancer therapy. The
      decreased oxygen capacity of blood resulting from anaemia affects virtually every
      organ and tissue system in the body, manifesting in numerous signs and symptoms
      that include fatigue, dyspnoea, palpitations, tachycardia, asthenia, anorexia,
      cold hypersensitivity and general weakness. Anaemia related to cancer may also
      cause cognitive dysfunction, leading to decreased mental alertness, poor
      concentration and memory problems. There is a close association between anaemia
      and overall quality of life (QoL) variables, and anaemia is an adverse prognostic
      factor in patients with cancer. Since anaemia can seriously compromise the QoL of
      cancer patients and is associated with decreased overall survival time, there is
      a strong need for effective and well-tolerated treatment strategies.
      Erythropoietic agents have been proven to be safe, well-tolerated and effective
      in the management of anaemia in patients with cancer. Epoetin therapy reduces
      transfusion requirements and increases haemoglobin levels in patients with solid
      tumours and haematological malignancies.

PMID- 15489560
TI  - Effects of treatment with epoetin beta on outcomes in patients with anaemia and
      chronic heart failure.
AB  - Anaemia is frequently found in patients with chronic heart failure (CHF) and has
      been associated with an increase in mortality and morbidity, impaired cardiac and
      renal function and a reduced quality of life (QoL) compared with non-anaemic CHF
      patients. Correction of anaemia with recombinant human erythropoietin (epoetin)
      has been associated with an improvement in CHF in both controlled and
      uncontrolled studies. The present study describes our findings in a series of 78
      consecutive patients with symptomatic CHF and anaemia (haemoglobin (Hb) level
      <12.0 g/dl) treated with epoetin beta and, if necessary, intravenous iron
      sucrose. Over a mean observation period of 20.7 +/- 12.1 months, mean Hb levels
      increased from 10.2 +/- 1.1 to 13.5 +/- 1.2 g/dl, p < 0.01. New York Heart
      Association (NYHA) functional class, left ventricular ejection fraction (LVEF)
      were significantly improved and the number of hospitalizations was significantly
      reduced with the period before treatment (all p < 0.01). Serum creatinine and
      creatinine clearance (CCr) were 2.2 +/- 0.9 mg/dl and 32.5 +/- 26.5 ml/min,
      respectively, at baseline, and remained stable over the observation period.
      Interestingly, >90% of the patients had concomitant mild-to-moderate chronic
      kidney disease at baseline and study end (CKD), as defined by the accepted
      diagnostic criterion of a CCr <60 ml/min. CONCLUSIONS: The correction of the
      anaemia with epoetin beta together with initial intravenous iron supplementation,
      resulted in significant improvements in NYHA class and cardiac function, and a
      reduction in hospitalization rate. Moreover, renal function was maintained stable
      in most patients.

PMID- 15489561
TI  - L-citrulline immunoreactivity reveals nitric oxide production in the electromotor
      and electrosensory systems of the weakly electric fish, Apteronotus
      leptorhynchus.
AB  - Weakly electric fish produce electric organ discharges (EODs) used for
      electrolocation and communication. In the brown ghost knifefish, Apteronotus
      leptorhynchus, several neuron types in brain regions that control the EOD or
      process electrosensory information express nitric oxide synthase (NOS). The
      present study used immunoreactivity for L-citrulline, a byproduct of the
      production of nitric oxide (NO) by NOS, to assess NO production in NOS-expressing
      neurons. A polyclonal antibody against L-citrulline produced specific labeling in
      most neuronal populations previously identified to express NOS. Specifically,
      several cell types that precisely encode temporal information and/or fire at high
      frequencies, including spherical cells in the electrosensory lateral line lobe,
      giant cells in layer VI of the dorsal torus semicircularis, and pacemaker and
      relay cells in the pacemaker nucleus, were strongly immunoreactive for L
      citrulline. This suggests that these neurons produced high levels of NO. Notably,
      electromotor neurons, which also strongly express NOS, were not immunoreactive
      for L-citrulline, suggesting that NOS did not produce high levels of NO in these
      neurons. No apparent differences in L-citrulline distribution or intensity were
      observed between socially isolated fish and fish exposed to playback stimuli
      simulating the presence of a conspecific. This suggests that social stimulation
      by electrocommunication signals is not necessary for high levels of NO production
      in many NOS-positive neurons. Future studies focusing on regulation of NO
      production in these systems, and the effects of NO on electrosensory processing
      and electromotor pattern generation will help elucidate the function of NO
      signaling pathways in this system.

PMID- 15489562
TI  - Social signals regulate gonadotropin-releasing hormone neurons in the green
      treefrog.
AB  - Animals coordinate their physiological state with external cues to appropriately
      time reproduction. These external cues exert effects through influences on the
      gonadotropin-releasing hormone neurons (GnRH), at the apex of the hypothalamus
      pituitary-gonad (HPG) axis. In green treefrogs, mating calls are important
      regulators of reproductive behavior and physiology. Reception of mating calls
      causes an increase in androgen levels, and androgens promote the production of
      mating calls, demonstrating a mutual influence between the communication and
      endocrine systems. In order to investigate the central nervous system correlates
      of social regulation of the HPG axis in green treefrogs, we exposed males to a
      mating chorus or a control stimulus (tones), counted the resulting number of
      septo-preoptic GnRH-immunoreactive cells (GnRH-ir), and measured changes in
      plasma androgens. We found that reception of the mating chorus caused an increase
      in the number of GnRH-ir cells. As previously shown, we also found that the
      reception of the mating chorus resulted in higher androgen levels, suggesting
      that the higher GnRH-ir cell number represents increased GnRH production and
      release. We suggest that mating calls are an important supplementary cue that
      promotes GnRH production and release within the context of GnRH regulation by
      seasonal cues. Previous studies have proposed a neuroanatomical link between the
      anuran auditory system and GnRH neurons. Our results demonstrate a functional
      role for this proposed sensory-endocrine circuit, and show for the first time an
      influence of acoustic signals on GnRH neurons.

PMID- 15489563
TI  - Comparisons of visual properties between tectal and thalamic neurons with
      overlapping receptive fields in the pigeon.
AB  - The present study is the first attempt to make comparisons of the visual response
      properties between tectal and thalamic neurons with spatially overlapping
      receptive fields by using extracellular recording and computer mapping
      techniques. The results show that in neuronal pairs about 70% of thalamic cells
      have excitatory receptive field alone, whereas 85% of tectal cells possess an
      excitatory receptive field surrounded by an inhibitory receptive field. In 70% of
      pairs the tectal cells are selective for direction of motion different from that
      which the thalamic cells prefer. Most thalamic cells prefer high speeds (80-160
      degrees/s), whereas tectal cells prefer intermediate (40 degrees/s) or low (10-20
      degrees/s) speeds. Photergic and scotergic cells exist in the thalamus but not in
      the tectum. These results provide evidence that tectal and thalamic cells extract
      different visual information from the same region of the visual field. The
      functional significance of these differences is discussed.

PMID- 15489564
TI  - Non-alcoholic steatohepatitis.
AB  - Non-alcoholic steatohepatitis (NASH) is an underdiagnosed liver disease
      characterized by steatosis, necroinflammation and fibrosis. This disease may
      eventually develop into cirrhosis and hepatocellular carcinoma. NASH is highly
      prevalent among obese individuals and among patients with diabetes mellitus type
      2. Non-alcoholic fatty liver (NAFL), a precursor of NASH, is the main cause of
      elevated serum liver enzymes among the general population. In NASH the liver is
      programmed to lipogenesis rather than to glycogenesis and herein insulin
      resistance plays a major role. Gradual weight loss, physical exercise and drugs
      that improve insulin sensitivity are potential therapies.

PMID- 15489565
TI  - The epidemiology of fatty liver.
AB  - There are insufficient data available on the epidemiology of fatty liver to
      design a complete and correct view of the prevalence, incidence and natural
      history of this disorder. This article, mainly based on the revision of recently
      published papers in this field, attempts to give an overview of the current
      findings on the epidemiology of fatty liver worldwide. The possible factors
      involved in the development of fat accumulation in the liver, and their potential
      role in the progression of the disorder will be also addressed.

PMID- 15489566
TI  - Mitochondrial injury in steatohepatitis.
AB  - Rich diet and lack of exercise are causing a surge in obesity, insulin resistance
      and steatosis, which can evolve into steatohepatitis. Patients with non-alcoholic
      steatohepatitis have increased lipid peroxidation, increased tumour necrosis
      factor-alpha (TNF-alpha) and increased mitochondrial beta-oxidation rates. Their
      in-vivo ability to re-synthesize ATP after a fructose challenge is decreased, and
      their hepatic mitochondria exhibit ultrastructural lesions, depletion of
      mitochondrial DNA and decreased activity of respiratory chain complexes. Although
      the mechanisms for these effects is unknown, the basal cellular formation of
      reactive oxygen species (ROS) may oxidize fat deposits to cause lipid
      peroxidation, which damages mitochondrial DNA, proteins and cardiolipin to
      partially hamper the flow of electrons within the respiratory chain. This flow
      may be further decreased by TNF-alpha, which can release cytochrome c from
      mitochondria. Concomitantly, the increased mitochondrial fatty acid beta
      oxidation rate augments the delivery of electrons to the respiratory chain. Due
      to the imbalance between a high electron input and a restricted outflow,
      electrons may accumulate within complexes I and III, and react with oxygen to
      form the superoxide anion radical. Increased mitochondrial ROS formation could in
      turn directly oxidize mitochondrial DNA, proteins and lipids, enhance lipid
      peroxidation-related mitochondrial damage, trigger hepatic TNF-alpha formation
      and deplete antioxidants, thus further blocking electron flow and further
      increasing mitochondrial ROS formation. Mitochondrial dysfunction plays an
      important role in liver lesions, through the ROS-induced release of both
      biologically active lipid peroxidation products and cytokines. In particular, the
      up-regulation of both TNF-alpha and Fas triggers mitochondrial membrane
      permeability and apoptosis. The ingestion of apoptotic bodies by stellate cells
      stimulates fibrogenesis, which is further activated by lipid peroxidation
      products and high leptin levels. Chronic apoptosis is compensated by increased
      cell proliferation, which, together with oxidative DNA damage, may cause gene
      mutations and cancer.

PMID- 15489567
TI  - Role of liver biopsy in the assessment of non-alcoholic fatty liver disease.
AB  - Assessments of liver biopsies are important in the diagnosis and management of
      non-alcoholic fatty liver disease. Histology remains the 'gold standard' for
      making the important distinction between simple steatosis, which is generally non
      progressive and readily reversible, and steatohepatitis, which has the potential
      to progress to severe fibrosis or cirrhosis. Liver biopsy may also identify other
      causes of liver disease in patients thought to have fatty liver disease and vice
      versa. Histological grading and staging of fatty liver disease require further
      study but these are potentially important approaches for studying disease
      severity and progression, particularly in the context of clinical trials to
      assess novel therapeutic approaches.

PMID- 15489568
TI  - Evaluation and management of non-alcoholic steatohepatitis.
AB  - Non-alcoholic fatty liver disease represents a spectrum of liver diseases which
      occurs in the absence of alcohol consumption in amounts considered injurious to
      the liver. Non-alcoholic fatty liver disease includes both non-alcoholic fatty
      liver and non-alcoholic steatohepatitis. We present an integrated approach that
      utilizes both clinical and laboratory studies to diagnose and manage a patient
      with suspected non-alcoholic steatohepatitis. The goals of treatment include (1)
      correction of the underlying risk factors, (2) avoidance of factors that promote
      progression of liver disease, and (3) specific treatment of non-alcoholic
      steatohepatitis.

PMID- 15489569
TI  - Unmasking a current medical pretender: anorexia nervosa in gastrointestinal
      practice.
AB  - Anorexia nervosa (AN) resembles the 'great pretenders' of medicine in the
      nineteenth century, syphilis and tuberculosis, by presenting occultly as a
      disorder of specific organs. Many physicians fail to identify the true primary
      cause, AN, which can mimic in its medical consequences gastrointestinal
      disorders, endocrine failure, pituitary tumors, or cancer. This is especially
      likely when the patients are older, have an established complex medical history,
      and challenge a specialist to find a medical cause and treatment, resulting in
      ordering more laboratory tests and medical instrumentation. Everyone suffers as a
      result, including the patient, the family, the frustrated physician, and the
      National Health Service, for whom the costs of medical care of these patients are
      enormous and out of proportion. Remembering that AN is as much a medical as a
      psychological disorder, assessing the patient with more time and expertise in
      history taking, and referring to a psychiatric consultant when National Institute
      for Clinical Excellence guidelines for identifying AN in non-mental health
      settings trigger suspicions, results in good outcome of the AN, cessation of
      ineffective gastrointestinal treatments, and substantial savings to the National
      Health Service.

PMID- 15489570
TI  - Making the diagnosis of coeliac disease: is there a role for push enteroscopy?
AB  - Coeliac disease is one of the most common genetically based diseases. The wide
      clinical spectrum of the disease and the availability of highly specific antibody
      testing have led to an increased number of patients undergoing gastroscopy with
      distal duodenal biopsies. Histological confirmation of the characteristic small
      bowel changes with partial or total villous atrophy remain the gold standard for
      making a diagnosis. Patients with positive antibodies but initially negative or
      uncertain biopsies pose a particular diagnostic dilemma. Due to the patchiness of
      the histological changes, push enteroscopy with jejunal biopsies can play a
      valuable role in this group of patients. Similarly, patients with refractory
      coeliac disease can benefit from push enteroscopy with jejunal biopsies.

PMID- 15489571
TI  - Management of hepatitis C after transplantation: a long way from success.
AB  - Recurrence of hepatitis C after transplantation is expected. Unfortunately, the
      outcome is poor in some, with as many as 25% of patients developing decompensated
      cirrhosis. Thus, developing treatment strategies to eradicate infection or slow
      the progression of hepatic fibrosis is crucial. The published data on treatment
      in this population is limited with viral response rates reported anywhere from 0
      48%. Furthermore, the poor tolerability of therapy is highlighted in the
      Berenguer article. These data emphasize the importance of developing effective
      non-interferon based therapies for the post-transplant patient.

PMID- 15489572
TI  - Anorexia nervosa in gastrointestinal practice.
AB  - OBJECTIVES: To characterize the demographic, psychosocial and prognostic features
      of patients with anorexia nervosa (AN) presenting to a gastroenterology service,
      and to compare them with patients presenting to an eating disorders unit.
      METHODS: A retrospective study set in two centres providing a local and tertiary
      service for gastroenterology and eating disorders. The notes of 20 consecutive
      patients with AN from each centre were compared. Comparison was made with a
      control group of 20 consecutive patients with slow transit constipation
      presenting to a gastroenterology service. RESULTS: Patients with AN who presented
      to a gastroenterology service were significantly older, had often seen a large
      number of hospital specialists, had a spectrum of gastrointestinal complaints,
      suffered a substantial delay in being diagnosed, and had undergone a
      significantly greater number of investigations and hospital admissions than AN
      patients attending an eating disorders unit. The parents of AN patients
      presenting to a gastroenterology clinic had a greater burden of physical and
      psychiatric illness than the parents in either of the other groups, and also
      tended to have separated when the patients were under the age of 10 years.
      Adverse prognostic factors among AN patients presenting to a gastroenterology
      clinic included older age at presentation, long history, unemployment, early
      parental separation and a body mass index less than 17. CONCLUSIONS: Patients
      with AN presenting to a gastroenterology service have profound psychosocial
      morbidity in excess of those presenting to a specialist eating disorders unit.
      Their diagnosis is often delayed. Early recognition and prompt referral to a
      specialist eating disorder unit should form the basis of management.

PMID- 15489573
TI  - Making the diagnosis of coeliac disease: is there a role for push enteroscopy?
AB  - BACKGROUND: Push enteroscopy is used in the assessment of refractory coeliac
      disease. However, its value in making the diagnosis of coeliac disease is still
      not defined. METHODS: Thirty-one patients (22 females, nine males) were recruited
      prospectively between September 2001 and October 2002; the age range was 20-80
      years (mean age, 52.7 years). All patients had symptoms suggestive of coeliac
      disease and positive serology but duodenal biopsy was not diagnostic. Twenty
      three patients had positive IgA or/and IgG antigliadin antibodies, eight patients
      had positive endomysial antibodies (EMA). All patients underwent enteroscopy with
      repeat quadrantic duodenal and additional jejunal biopsies. RESULTS: All samples
      were reviewed by a single, blinded, histopathologist. There were no cases of
      coeliac disease diagnosed on further biopsy in patients who had a positive
      gliadin antibody in isolation. In the eight EMA-positive cases repeat biopsy
      demonstrated coeliac disease in five patients. In 3/5 cases the changes were
      confined to the jejunal biopsies only. CONCLUSION: EMA-positive patients with
      initially normal histology should have a further duodenal biopsy. In our series
      three of the five newly diagnosed coeliac disease patients only had villous
      atrophy demonstrable in the jejunum. There may be a role for push enteroscopy in
      making the diagnosis of coeliac disease. However, further prospective studies are
      needed.

PMID- 15489574
TI  - Association between enhanced soluble CD40 ligand and prothrombotic state in
      inflammatory bowel disease.
AB  - BACKGROUND: Inflammatory bowel disease is associated with an increased incidence
      of thromboembolic complications. The aim of this study was to investigate the
      role of the soluble CD40 ligand (sCD40L), which displays prothrombotic
      properties, in patients with ulcerative colitis (UC) and Crohn's disease (CD) in
      comparison with inflammatory and healthy controls. METHODS: Plasma levels of
      sCD40L, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT) complex and
      soluble P-selectin were measured in 104 inflammatory bowel disease patients (54
      ulcerative colitis and 50 Crohn's disease), in 18 cases with other causes of
      intestinal inflammation and in 80 healthy controls using commercially available
      enzyme-linked immunosorbent assays. Plasma levels of sCD40L were correlated with
      disease activity, type, localization and treatment as well as with the measured
      thrombophilic parameters. RESULTS: CD patients had significantly higher sCD40L
      levels than both groups of controls (CD vs HC P < 0.001; CD vs non-IBD P < 0.05).
      UC patients had higher but not significantly different sCD40L levels compared
      with the controls. Both UC and CD patients with active disease had significantly
      higher sCD40L levels in comparison with patients with inactive disease. Plasma
      levels of sCD40L were correlated with platelet count (r = 0.27, P = 0.001). They
      also showed a correlation with prothrombin F1+2 (r = 0.16, r = 0.03) and TAT (r =
      0.15, r = 0.04) as well as with P-selectin (r = 0.19, P = 0.01). CONCLUSIONS: The
      increased sCD40L plasma levels may represent, at least in some degree, a
      molecular link between inflammatory bowel disease and the procoagualant state.

PMID- 15489575
TI  - Epidemiology of inflammatory bowel disease in adults who refer to
      gastroenterology care in Romania: a multicentre study.
AB  - AIM: The Romanian Society of Gastrointestinal Endoscopy developed a multicentre,
      prospective study to evaluate the frequency and epidemiological features of
      inflammatory bowel disease (IBD) in an adult population that refers to
      gastroenterology centres in Romania. MATERIAL AND METHODS: Eighteen centres with
      adequate diagnostic and therapeutic facilities uniformly distributed across
      Romania reported through a proforma the new and old IBD cases between 1 June 2002
      and 1 June 2003. The rates of incidence and prevalence of ulcerative colitis (UC)
      and Crohn's disease (CD) have been reported per 100 000 inhabitants.
      Epidemiological features and disease characteristics were analysed. RESULTS:
      During the study, 407 cases of UC (163 incident cases) and 254 cases of CD (85
      incident cases) were identified. The incidence in the referral population was
      0.97/100 000 and 0.50/100 000 for UC and CD, respectively, whereas the
      prevalences was 2.42/100 000 and 1.51/100 000 for UC and CD, respectively. A
      slight male predominance, wider age distribution and predominant urban residence
      were the main demographic features of incident cases; smoking and
      appendectomy/appendicitis were infrequent in UC, while a higher proportion of CD
      patients were smokers. Lower rates of severe, extensive or complicated IBD were
      noted as compared with the literature. CONCLUSION: Incidence and prevalence rates
      of IBD in Romania are low. Predominant male involvement and a wider distribution
      of incident cases were the main demographic features in our population. IBD in
      our patients had a more 'benign' course as compared with the literature, with
      lower rates of severe, extensive or complicated disease and a small proportion of
      patients who need surgery.

PMID- 15489576
TI  - Doctor-patient interaction for irritable bowel syndrome in primary care: a
      systematic perspective.
AB  - BACKGROUND AND AIMS: Irritable bowel syndrome (IBS) is defined by specific
      validated symptom criteria and encompasses several different underlying
      pathophysiological mechanisms that express a common set of symptoms. However, IBS
      is poorly understood by patients. We aimed to explore how a diagnosis of IBS
      affects the interaction between patients and their physicians. METHODS: A
      comprehensive literature search for studies in the English language addressing
      this issue was conducted using Medline, PubMed, Cochrane Database, Psychinfo,
      Cinahl, Embase, Web of Science and manual recursive search of reference lists.
      Investigators reviewed and abstracted data from articles fulfilling our inclusion
      criteria: primary care patients, all ages, gender and ethnic groups diagnosed
      with IBS by a general practitioner (GP). RESULTS: Retrieval of 121 articles
      generated only four that met inclusion criteria. Research methods of three
      studies relied solely on qualitative subjective, anecdotal patient narratives, a
      bias in favor of patients' negative opinion, absence of objective physician
      diagnostic criteria, pre-testing questions for two studies, follow-up and patient
      verification of accounts for accuracy. The fourth study included objective
      physician diagnostic criteria, quantitative measures, a pre-testing
      questionnaire, and both patient and doctor perspectives. There was a disparity
      between patient and GP perception regarding the nature, severity and consequences
      of IBS in primary care, leading patients to perceive this interaction as one of
      dissatisfaction. The fourth study revealed GP management of IBS mostly meets
      patient's expectations areas of concern centered on etiology, diagnostic criteria
      and dietary advice. Disparity seems to lie with the physician, who needs to
      provide more trust, knowledge, and sympathy, create rapport and be forthcoming
      with information, while keeping information simple and understandable. Patient
      dissatisfaction stems from the actual information provided and how this is
      communicated. CONCLUSIONS: There is evidence that some IBS patients in primary
      care experience dissatisfaction and negative attitudes in GP interactions. Future
      research should take into account personality attributes and cross-situational
      stability in addition to methodological implications of studies. GPs may be the
      first avenue for IBS patients to vent their frustration, and appropriate
      education programs for optimal management of patients with IBS are needed in
      primary care.